PMID- 19837453
TI  - Influence of LED irradiance on flexural properties and Vickers hardness of resin
      based composite materials.
AB  - OBJECTIVE: To investigate the effect of irradiance through choice of LED light
      curing unit (LCU) and fiber-optic tip on the mechanical properties of
      methacrylate resin-based composites (RBCs). METHODS: Rectangular bar-shaped
      specimens (25 mm x 2 mm x 2 mm) of four RBCs, irradiated from one side for the
      manufacturer's recommended times with one of two LED LCUs, and with either 8 or
      13 mm tip diameter, were tested in three-point bend for flexural strength and
      modulus of elasticity; Vickers hardness was measured on top and bottom surfaces,
      on overlapped and non-overlapped irradiation sites. The effects and interactions
      of all factors were examined by analysis of variance. RESULTS: While the
      materials tested differed significantly for all properties (P < 1 x 10(-6)),
      there was no significant effect for LCU, tip, or irradiance for flexural strength
      or modulus of elasticity. For hardness, the only significant effect overall was
      due to irradiance on the bottom surface. CONCLUSIONS: Both LCUs and both tips
      could be used to give adequate top surface hardness, but the recommended maximum
      increment thickness is too great for adequate cure at the bottom with the tested
      LCUs at the recommended times. An extended experimental design would be valuable
      to test behavior at much elevated irradiances.

PMID- 19837454
TI  - Immunosuppression-associated lymphoma in IBD.

PMID- 19837456
TI  - Comparison of three methods for quantifying topographic complexity on rocky
      shores.
AB  - Topographic complexity (TC) is an important factor in determining community
      structure in aquatic habitats and there are numerous methods for its estimation.
      Here we assess and compare three (chain, divider and distance-wheel) methods
      across different users and substrata over scales of 78-1030 mm. All three
      techniques showed the same basic trend in TC over different substrata. However,
      the chain took approximately 1.5x as long to use, at larger-scales (>271 mm), as
      the other techniques and resulted in highly variable TC estimates. The chain and
      divider techniques both have the potential to miss relevantly scaled TC depending
      on the survey starting point, a disadvantage not suffered by the distance-wheel.
      TC measured using the distance-wheel was approximately 1.8x that recorded by the
      divider technique and significantly (P<0.05) less variable compared with the
      chain technique. The distance-wheel was rapid and easy to use, superior in
      accessing awkward topographies and has considerable potential for improvement. It
      is recommended as a technique for estimating the TC of rock-surfaces at scales
      >50 mm.

PMID- 19837457
TI  - Therapeutic effects of anticoagulant agents on preeclampsia in a murine model
      induced by phosphatidylserine/phosphatidylcholine microvesicles.
AB  - Preeclampsia (PE) is a placenta-mediated pregnancy complication that results in
      high maternal and neonatal mortality and morbidity worldwide. Currently, there is
      no satisfactory pharmacotherapeutic treatment to stop the PE progression. In this
      study, we investigated the therapeutic effects of anticoagulant agents, including
      annexin V, heparin, and a fusion protein of annexin V and hirudin (AND), in a
      murine PE model induced by intravenous injection of
      phosphatidylserine/phosphatidylcholine (PS/PC) microvesicles. Compared with the
      control pregnant animals, the pregnant mice injected with PS/PC presented PE-like
      symptoms, including elevated systolic blood pressure, proteinuria, and reduction
      of antithrombin III and blood platelets. However, the PE-like symptoms were
      significantly alleviated after the PS/PC-injected mice were treated with annexin
      V, AND, or heparin. Furthermore, fibrin deposition in the placentas in the
      anticoagulant treated mice was remarkably improved, compared with that in the
      mice injected with PS/PC alone. The data demonstrate that anticoagulants are
      effective to prevent the occurrence of PE in the murine model and also suggest
      that hypercoagulation in the placenta is a contributing factor in the
      pathogenesis of PE.

PMID- 19837458
TI  - The species sensitivity distribution approach compared to a microcosm study: a
      case study with the fungicide fluazinam.
AB  - We assessed the sensitivity of freshwater organisms (invertebrates and algae) to
      the fungicide Shirlan (active ingredient fluazinam) in single-species laboratory
      tests and in microcosms. Species sensitivity distribution (SSD) curves were
      constructed by means of acute toxicity data for 14 invertebrate species, since
      algae were much less sensitive. The EC(10)-based SSD gave a median HC(5) value of
      0.6microgL(-1) and a 90% confidence interval of 0.1-1.9 microgL(-1). The EC(50)
      based SSD gave a median HC(5) value of 3.9 microgL(-1) (90% confidence interval:
      0.9-9.9 microgL(-1)). The microcosms were treated four times with Shirlan
      (concentration range: 0.4-250 microgL(-1)). Responses of the microcosm
      communities were followed. The 2 microgL(-1) treatment was the no-observed-effect
      concentration (NOEC(microcosm)). The 10 microgL(-1) treatment resulted in short
      term effects on a few zooplankton taxa. Clear effects were observed at 50 and 250
      microgL(-1). The responses in the microcosms were in line with the toxicity data
      for the tested lab species. The median EC(10)-based HC(5) and the lower limit
      EC(50)-based HC(5) were lower, and the median EC(50)-based HC(5) was slightly
      higher than the NOEC(microcosm). This is consistent with other studies that
      compared SSDs with responses in model ecosystems that received repeated
      applications of pesticides.

PMID- 19837459
TI  - Seclusion: the perspective of nurses.
AB  - Knowledge of how nurses experience the process of secluding a patient can be
      useful in improving the quality of patient care and in the prevention of work
      related stress in nurses. This study describes personal experiences of nurses
      throughout the seclusion process. The emotions which came to surface in semi
      structured interviews with 8 nurses were categorized in three main themes
      (Tension, Trust and Power) and a stress response curve was identified in the
      seclusion process, with specific feelings in each phase. Feelings denied in
      former studies such as feeling superior, anger and disgust were found in the
      interviews in this study.

PMID- 19837460
TI  - A binding question: the evolution of the receptor concept.
AB  - In present-day pharmacology and medicine, it is usually taken for granted that
      cells contain a host of highly specific receptors. These are defined as proteins
      on or within the cell that bind with specificity to particular drugs, chemical
      messenger substances or hormones and mediate their effects on the body. However,
      it is only relatively recently that the notion of drug-specific receptors has
      become widely accepted, with considerable doubts being expressed about their
      existence as late as the 1960s. When did the receptor concept emerge, how did it
      evolve and why did it take so long to become established?

PMID- 19837461
TI  - Assessment and treatment of bipolar II postpartum depression: a review.
AB  - OBJECTIVE: This paper critically reviews the current literature on the detection,
      diagnosis, and treatment of bipolar II postpartum depression. METHOD: A Pub-Med
      search (1998-2009), using the search terms 'postpartum depression', 'postpartum
      depression AND screening/detection/diagnosis/treatment', 'bipolar I AND
      postpartum depression', 'bipolar II AND postpartum depression', 'postpartum
      hypomania', and 'postpartum hypomania AND screening', was carried out. The
      reference lists of articles identified were also searched to select other
      relevant publications. RESULTS: Brief hypomanic symptoms occur in the early
      puerperium in approximately 15% of women. Despite preliminary evidence that
      postpartum depression in some patients may be a manifestation of bipolar II
      disorder or bipolar disorder NOS, there are no screening instruments to
      differentiate unipolar from bipolar depression arising in pregnancy or the
      postpartum. Also lacking are evidence-based treatment options specifically
      targeted to treat bipolar II postpartum depression. CONCLUSIONS: Research into
      postpartum mood disorders has focused primarily on major depressive disorder,
      bipolar I disorder, and puerperal psychosis, and has largely ignored the study of
      bipolarity beyond bipolar I disorder. The clinical and research implications of
      the misdiagnosis of bipolar II depression as major depressive disorder in the
      postpartum period are discussed.

PMID- 19837462
TI  - GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors.
AB  - G-protein-coupled receptors (GPCRs) are the most versatile receptor family as
      they have the ability to respond to chemically diverse ligands. Despite intensive
      efforts during the past two decades, there are still more than 100 orphan GPCRs
      for which endogenous ligands are unknown. Recently, GPR109A, GPR109B and GPR81,
      which form a GPCR subfamily, have been deorphanized. The physiological ligands of
      these receptors are the ketone body 3-hydroxy-butyrate, the metabolite 2-hydroxy
      propanoate (lactate) as well as the beta-oxidation intermediate 3-hydroxy
      octanoate. Thus, this receptor subfamily is activated by hydroxy-carboxylic acid
      ligands which are intermediates of energy metabolism. All three receptors are
      predominantly expressed in adipocytes and mediate antilipolytic effects. In this
      article, we propose that the hydroxy-carboxylic acid structure of their
      endogenous ligands is the defining property of this receptor subfamily and that
      hydroxy-carboxylic acid receptors function as metabolic sensors which fine-tune
      the regulation of metabolic pathways.

PMID- 19837463
TI  - Glutamate-based antidepressants: 20 years on.
AB  - Depression is a chronic recurring illness that affects more than 120 million
      people worldwide. Drugs increasing the synaptic availability of serotonin and
      norepinephrine (biogenic amine-based agents) have been used to treat depression
      for more than 50 years. However, significant symptom improvement requires > or =2
      4 weeks of treatment and a first course of therapy provides symptom relief to
      only 60-65% of patients. Roche and Evotec recently announced plans to develop N
      methyl-D-aspartate (NMDA) receptor antagonists targeting the NR2B subtype for
      treatment-resistant depression. This announcement closely follows a report that
      another NR2B antagonist, traxoprodil (CP 101 606), has antidepressant effects in
      patients unresponsive to a serotonin selective reuptake inhibitor, as well as
      reports of rapid and sustained antidepressant effects following a single
      injection of the NMDA antagonist ketamine. Here we describe evidence that
      glutamate-based therapies might represent an effective alternative to biogenic
      amine-based agents for depression and provide perspectives on the development of
      these agents.

PMID- 19837464
TI  - Elucidating the elite: mechanisms of control in HIV-1 infection.
AB  - In patients with progressive disease, untreated HIV-1 infection is characterized
      by high viral loads and decreasing CD4(+)T cell counts which lead to
      opportunistic infection and other AIDS-defining illness. A rare subset of
      patients termed 'elite controllers' (ECs) maintain control over viremia and often
      retain normal CD4(+)T cell levels without treatment with antiretroviral drugs.
      For the most part these patients are infected with replication-competent, fit
      virus. Factors such as strong, polyfunctional cytotoxic T lymphocyte (CTL)
      responses and retention of T cell proliferative ability appear to be important in
      control of HIV-1. Defining what enables ECs to control viral replication will aid
      in the development of effective vaccine and treatment regimens. This review will
      discuss differences between ECs and progressors while emphasizing recent findings
      on the immunological response of ECs to HIV-1.

PMID- 19837455
TI  - Lymphoproliferative disorders in patients receiving thiopurines for inflammatory
      bowel disease: a prospective observational cohort study.
AB  - BACKGROUND: Reports of an increased risk of lymphoproliferative disorders in
      patients receiving thiopurines for inflammatory bowel disease are controversial.
      We assessed this risk in a prospective observational cohort study. METHODS:
      19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had
      Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified
      inflammatory bowel disease, were enrolled in a nationwide French cohort by 680
      gastroenterologists, who reported details of immunosuppressive therapy during the
      observation period, cases of cancer, and deaths. The risk of lymphoproliferative
      disorder was assessed according to thiopurine exposure. Median follow-up was 35
      months (IQR 29-40). FINDINGS: At baseline, 5867 (30.1%) of patients were
      receiving, 2809 (14.4%) had discontinued, and 10,810 (55.5%) had never received
      thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed,
      consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin
      lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder
      were 0.90 per 1000 (95% CI 0.50-1.49) patient-years in those receiving, 0.20/1000
      (0.02-0.72) patient-years in those who had discontinued, and 0.26/1000 (0.10
      0.57) patient-years in those who had never received thiopurines (p=0.0054). The
      multivariate-adjusted hazard ratio of lymphoproliferative disorder between
      patients receiving thiopurines and those who had never received the drugs was
      5.28 (2.01-13.9, p=0.0007). Most cases associated with thiopurine exposure
      matched the pathological range of post-transplant disease. INTERPRETATION:
      Patients receiving thiopurines for inflammatory bowel disease have an increased
      risk of developing lymphoproliferative disorders. FUNDING: Programme Hospitalier
      de Recherche Clinique National (AOM05157), Association Francois Aupetit,
      Delegation Inter-regionale de la Recherche clinique Ile de France-Assistance
      Publique Hopitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de
      Recherche de la Societe Nationale Francaise de Gastro-enterologie.

PMID- 19837465
TI  - Multiple ways of targeting APOBEC3-virion infectivity factor interactions for
      anti-HIV-1 drug development.
AB  - HIV-1 infections and the resulting AIDS pandemic remain a global challenge in the
      absence of a protective vaccine and because of rapid selection of drug-resistant
      viral variants in response to all currently available antiviral therapies. The
      development of new and highly active antiviral agents would greatly facilitate
      effective clinical management of HIV-1 infections and delay the onset of AIDS.
      Recent advances in our understanding of intracellular immunity conferred by host
      cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) and the mechanism by which
      the virally encoded virion infectivity factor (Vif) protein induces their
      proteasomal degradation provide fresh opportunities for the development of novel
      antiviral treatments. Interestingly, the Vif-A3G and Vif-A3F interactions that
      overcome this host defense mechanism are structurally distinct and provide two
      potential targets for antiviral drug development. This review provides an
      overview of current knowledge of APOBEC3-Vif interactions and recent efforts to
      target these interactions for antiviral drug development.

PMID- 19837467
TI  - Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer.
AB  - Nanoscale drug delivery systems using liposomes and nanoparticles are emerging
      technologies for the rational delivery of chemotherapeutic drugs in the treatment
      of cancer. Their use offers improved pharmacokinetic properties, controlled and
      sustained release of drugs and, more importantly, lower systemic toxicity. The
      commercial availability of liposomal Doxil and albumin-nanoparticle-based
      Abraxane has focused attention on this innovative and exciting field. Recent
      advances in liposome technology offer better treatment of multidrug-resistant
      cancers and lower cardiotoxicity. Nanoparticles offer increased precision in
      chemotherapeutic targeting of prostate cancer and new avenues for the treatment
      of breast cancer. Here we review current knowledge on the two technologies and
      their potential applications to cancer treatment.

PMID- 19837466
TI  - A novel method for determining the inhibitory potential of anti-HIV drugs.
AB  - In the absence of cure, most HIV-1-infected individuals will require lifelong
      treatment. It is therefore essential to optimize highly active antiretroviral
      therapy. Recent research has shown that the slope parameter or Hill coefficient,
      which describes the steepness of a dose-response curve, is a critical missing
      dimension in the evaluation of the activity of antiviral drugs. Based on this
      finding, instantaneous inhibitory potential (IIP) has been derived as a new
      measure of antiviral drug activity. IIP incorporates the slope parameter and thus
      is a more accurate pharmacodynamic measure of antiviral activity than current
      measures such as IC(50) and inhibitory quotient. Determining how to use IIP to
      predict the in vivo efficacy of anti-HIV-1 drugs is nevertheless important. This
      article discusses recent advances in in vitro measures of antiviral activity and
      the therapeutic implications of the dose-response curve slope and IIP.

PMID- 19837468
TI  - Dipeptidyl peptidase inhibitors, an emerging drug class for inflammatory disease?
AB  - Dipeptidyl peptidase (DPP)-4 is a member of the S9b serine protease family, which
      also includes DPP8 and DPP9. DPP4 cleaves a number of regulatory factors,
      including chemokines and growth factors. DPP4 inhibitors have recently emerged as
      an effective treatment option for type 2 diabetes. Early in vitro studies
      demonstrated that DPP4 inhibitors inhibit T-cell proliferation and cytokine
      production, leading to their investigation in numerous pre-clinical models of
      inflammatory diseases, including arthritis, multiple sclerosis and inflammatory
      bowel disease. Recent data suggest that the early DPP4-specific inhibitors might
      also bind DPP8 and DPP9, thus exerting their effects through non-specific
      binding. This review highlights recent insights into the applicability of DPP
      inhibitors as novel pharmacological agents for inflammatory disease.

PMID- 19837469
TI  - Molecular layers underlying cytoskeletal remodelling during cortical development.
AB  - During neural development, the cytoskeleton of newborn neurons undergoes
      extensive and dynamic remodelling to facilitate the sequential steps of
      neurogenesis, cell migration and terminal differentiation. It is clear from
      studying the mechanisms that precipitate these functions that different
      configurations of the cytoskeleton prefigure the correct execution of each step
      and define cohorts of proteins the functions of which are indispensable for the
      control of neuronal migration but not terminal differentiation. These
      combinatorial protein functions are also predetermined by regulated gene
      expression and the precise subcellular localisation of their protein products.
      Here, we expand on this view in the context of recent data on how the
      cytoskeleton is regulated during the maturation of cortical neurons within the
      developing brain.

PMID- 19837470
TI  - Optimization of an isolated perfused rainbow trout liver model: Clearance studies
      with 7-ethoxycoumarin.
AB  - To date, research with isolated perfused fish livers has been limited by the
      relatively short time period during which stable performance can be achieved. In
      the present study, modifications to existing methods were employed with the goal
      of extending the usable life of an isolated perfused trout liver preparation.
      Liver performance was evaluated by measuring O(2) consumption (VO(2)), vascular
      resistance, K(+) leakage, glucose flux, lactate flux, and clearance of a model
      metabolic substrate, 7-ethoxycoumarin (CL(H,7-EC)). Livers perfused with
      solutions containing 15, 38, or 150microM bovine serum albumin (BSA) exhibited
      relatively stable physiological performance for up to 10h. CL(H,7-EC) decreased
      rapidly between 1 and 2h in all livers tested, possibly due in part to
      accumulation of 7-EC within the tissue. CL(H,7-EC) declined slowly thereafter,
      decreasing by 30-40% between 2 and 10h. A linear equation was subsequently
      developed to correct measured levels of clearance for this decrease in metabolic
      activity over time. To illustrate the value of this preparation, experiments were
      conducted to examine the effects of protein binding on 7-EC clearance. Clearance
      rates corrected for declining activity (CL(H,7-EC,CORR)) changed in nearly direct
      proportion to changes in the free concentration of 7-EC efferent to the liver, as
      predicted by theoretical models of liver function. Additional studies were
      performed to characterize the concentration-dependence of 7-EC clearance. The
      rate of substrate disappearance from the perfusate increased in proportion to the
      total concentration of 7-EC afferent to the liver resulting in constant levels of
      CL(H,7-EC,CORR). CL(H,7-EC,CORR) values for four livers averaged 12.1+/-2.5mL/h/g
      liver (mean+/-SD, n=57 individual determinations) and were in good agreement with
      an estimate of hepatic clearance obtained by extrapolating published in vitro
      data from isolated trout hepatocytes. The extended viability of isolated trout
      livers achieved in this study creates new opportunities for research on hepatic
      function in fish.

PMID- 19837471
TI  - Trends in Campylobacter incidence in broilers and humans in six European
      countries, 1997-2007.
AB  - The objective of this study was to examine incidences of Campylobacter in
      broilers and humans, and to describe seasonal variation and long-term trends by
      comparing longitudinal surveillance data in six Northern European countries
      (Denmark, Finland, Iceland, Norway, Sweden and the Netherlands). Due to high
      degree of seasonality and autocorrelation, seasonally adjusted (de-seasonalized)
      and trend adjusted data (de-trended) were used for comparing incidences within
      and between the six countries. De-seasonalized time series were obtained by
      fitting the incidence time series to mean monthly temperature and then removing
      this effect from the data. Long-term trends were fitted to the de-seasonalized
      time series. The incidence of Campylobacter colonization in broiler flocks and
      incidence of campylobacteriosis in humans showed a concordant seasonality for all
      the countries. There was a strong association between the incidence in both
      broilers and humans in a given month and the mean temperature of the northern
      hemisphere in the same month, as well as the preceding month, as shown by the
      cross-correlations and the chosen Generalized Additive Model. Denmark and Sweden
      showed a steadily decreasing trend for Campylobacter in broilers and human
      campylobacteriosis in the period 2001-2007. In Iceland, there was a decreasing
      trend for campylobacteriosis in humans from 1999 to 2007, whilst the broiler
      trend for Campylobacter was stable from 2001 to 2004, then falling thereafter. In
      Norway, the human campylobacteriosis trend showed a steady increase throughout
      the period. On the other hand, the Norwegian broiler trend for Campylobacter
      showed a decrease from 2001 until 2004, but was thereafter stable. There was no
      significant decrease or increase in incidence for human campylobacteriosis in the
      Netherlands, and the trend for Campylobacter in broilers was close to stable. The
      seasonality seen in broiler and human closely follows the temperature, and was
      probably caused, at least partly, by temperature related factors.

PMID- 19837472
TI  - Quadrimodal treatment of high-risk T1 and T2 bladder cancer: transurethral tumor
      resection followed by concurrent radiochemotherapy and regional deep
      hyperthermia.
AB  - BACKGROUND AND PURPOSE: To assess the safety and effectiveness of treating high
      risk T1 and T2 bladder cancer with transurethral resection (TUR-BT) followed by
      radiochemotherapy (RCT) combined with regional deep hyperthermia (RHT). MATERIAL
      AND METHODS: Between 2003 and 2007, 45 patients were enrolled. After TUR-BT
      patients received radiotherapy (RT) of the bladder and regional lymph nodes with
      50.4 Gy, and a boost to the bladder of 5.4-9 Gy. RCT was applied to 43/45
      patients. RHT was administered once weekly. Response was re-evaluated 6 weeks
      after RT by restaging-TUR. Toxicity was graded with the CTCAE, version 3.0. QoL
      was evaluated by a dedicated questionnaire. RESULTS: The median follow-up was 34
      months (range 12-60). The median number of hyperthermia treatments was 5 (range 1
      7). Acute toxicity grades 3 and 4 occurred in 20% (9/45) and 9% (4/45),
      respectively. Late toxicity grades 3/4 were seen in 24% (11/45). Complete
      response rate was 96% (43/45). Local recurrence-free survival was 85%, overall
      survival was 80%, disease-specific survival was 88%, metastasis-free survival was
      89%, and the bladder-preserving rate was 96% (43/45) at 3 years. Eighty percent
      (24/30) were at least mostly satisfied with their bladder function. CONCLUSIONS:
      The quadrimodal treatment was feasible and well tolerated. Local control and
      bladder-preserving rates were encouraging.

PMID- 19837473
TI  - Effect of small group treatment of the modified constraint induced movement
      therapy for clients with chronic stroke in a community setting.
AB  - This study investigated the effects of the group treatment component of the
      modified constraint induced movement therapy (mCIMT) protocol for clients with
      chronic stroke in a community setting. A within-subjects longitudinal study was
      conducted to which eight participants with chronic stroke being treated in a
      community setting in Hong Kong were recruited. Ten 3-h group sessions were
      conducted on two occasions within a four-week period, with four participants per
      group. Participants' less-affected hands were restrained in a mitt, with a target
      of wearing it for 4h per weekday. Laboratory based tests and the Motor Activity
      Log (MAL) were used repeatedly to measure participants' hemiparetic upper
      extremity functions and the use of the limb in real-life on four measurement
      occasions: at baseline (four weeks before training), pre-test (one day before
      training), post-test (one day after training), and follow-up (four weeks after
      training). The Wilcoxon signed-rank test showed participants' baselines were
      stable four weeks before the intervention. The Friedman test found significant
      differences between pre-test, post-test and follow-up in the Box and Block Test
      (BBT), the total score, grasp and pinch subscores of the Action Research Arm Test
      (ARAT), and the Hong Kong Version of the Functional Test for the Hemiplegic Upper
      Extremity (FTHUE-HK), the Wolf Motor Function Test (WMFT), and the MAL. All these
      gains were maintained during the 1-month follow-up. The small group treatment
      component of the mCIMT was found to be effective, feasible, and capable of
      improving both motor performance and functional use of the affected upper
      extremity for patients with chronic stroke in a community setting.

PMID- 19837474
TI  - Proteolytic activity, mycotoxins and andrastin A in Penicillium roqueforti
      strains isolated from Cabrales, Valdeon and Bejes-Tresviso local varieties of
      blue-veined cheeses.
AB  - High quality local varieties of blue-veined cheese are made in the villages of
      the valleys of Cabrales, Valdeon and Bejes-Tresviso in North Spain. Penicillium
      roqueforti strains have been isolated from each of those blue cheeses and
      compared with the collection strain P. roqueforti CECT 2905 (ATCC 10110) and a
      strain 'Valdeon-industrial' used for large scale production of Valdeon cheese.
      Using molecular genetics techniques and 5.8S and 18S rRNAs and the D1-D2 regions
      of 28S rRNA all strains were identified as authentic P. roqueforti. These strains
      from local varieties of blue cheese could be distinguished from the Valdeon
      industrial strain and the control strain CECT 2905 by the mitochondrial DNA
      restriction pattern. The industrial strain showed high levels of aspartylprotease
      AspA, whereas the culture collection strain showed barely detectable levels of
      this enzyme, as shown by proteolysis tests and by immunodetection with anti-AspA
      antibodies. The lipolytic activity was similar in the strains isolated from the
      three types of local blue cheeses. The strains isolated from the local varieties
      of the blue cheese produced moderate levels of PR toxin, whereas the Valdeon
      industrial strains showed a higher content of this mycotoxin. All strains (except
      the control strain CECT 2905) showed similar levels of roquefortine C. The
      antitumoral compound andrastin A was produced by all strains at different levels.
      P. roqueforti CECT 2905 showed high ability to synthesize this compound.
      Andrastin A was present in all industrial and local varieties of blue cheese. The
      content of andrastin A was similar to that of other well-known blue cheeses from
      France and Denmark.

PMID- 19837476
TI  - Explaining evolution of plant communication by airborne signals.
AB  - In spite of initial doubts about the reality of 'talking trees', plant resistance
      expression mediated by volatile compounds that come from neighboring plants is
      now well described. Airborne signals usually improve the resistance of the
      receiver, but without obvious benefits for the emitter, thus making the
      evolutionary explanation of this phenomenon problematic. Here, we discuss four
      possible non-exclusive explanations involving the role of volatiles: in direct
      defense, as within-plant signals, as traits that synergistically interact with
      other defenses, and as cues among kin. Unfortunately, there is a lack of
      knowledge on the fitness consequences of plant communication for both emitter and
      receiver. This information is crucial to understanding the ecology and evolution
      of plant communication via airborne cues.

PMID- 19837475
TI  - Reading between the LINEs to see into the past.
AB  - Transposable elements (TEs) are an important source of genome diversity and play
      a crucial role in genome evolution. A recent study by Zhao et al. describes novel
      patterns of TE diversification in the genome of the extinct mammoth Mammuthus
      primigenius. Analysis of Mammuthus has provided a unique genome landscape, a
      pivotal species for understanding TEs and genome evolution and hints at the
      diversity we verge on discovering by expanding our taxonomic sampling among
      genomes. Strategies based on this work might also revolutionize investigations of
      the interface between TE dynamics and genome diversity.

PMID- 19837477
TI  - Determining minimum sticking efficiencies of six environmental Escherichia coli
      isolates.
AB  - In health impact assessments, the sticking efficiency of a bacteria or virus
      population largely determines the transported distance of that biocolloid
      population, and hence, the potential health impact. However, at the same time,
      one of the most difficult parameters to estimate is the lower value of the
      sticking efficiency that should be used in calculating the health impact. In this
      paper, we introduce the concept of the minimum sticking efficiency (alpha(i))
      value of a bacteria population, including a method to determine the minimum
      sticking efficiency. Thereto, sticking efficiency distributions of 6
      environmentally isolated Escherichia coli strains were determined by carrying out
      laboratory column experiments over a transport distance of about 5m. Experiments
      were conducted in de-mineralized (DI) water and in artificial groundwater (AGW).
      Sticking efficiencies were calculated for column segments (at varying distances
      from top of column) and fractions of total bacteria mass input in each segment
      were estimated by mass balance. The sticking efficiencies were highest close to
      the top of the column, near the point of bacteria mass input (0.103-0.352 in DI,
      and 1.034-9.470 for AGW) and reduced with distance with the lowest alpha(i)
      values (10(-5)-0.06 in DI and 0.006-0.283 in AGW) determined at the two most
      distant column segments (between 2.33 and 4.83 m from the top of the column).
      Power-law distributions best described the relationship between fraction of cells
      retained, F(i), and alpha(i). The minimum sticking efficiency was defined as the
      sticking efficiency belonging to a retained bacteria fraction of 0.001% of the
      original bacteria mass (total number of cells) flowing into the column (F=10(
      5)), and coinciding with a 99.999% reduction of the original bacteria mass, and
      minimum sticking efficiencies were extrapolated from the fitted power-law
      distributions. In the DI experiments, minimum sticking efficiency values ranged
      from as low as 10(-9) (for E. coli strain UCFL-94) to 10(-2) (for E. coli strain
      UCFL-348); in the AGW experiments, minimum sticking efficiency values ranged from
      10(-6) (for strain UCFL-94) to > or =1(for strain UCFL-348). We concluded that in
      quantifying health impacts of biocolloids traveling in aquifers, the concept of
      the minimum sticking efficiencies, and the percentage of individual biocolloids
      of a total population having such low sticking efficiency, together with an
      inactivation rate coefficient, can serve as a useful tool to determine the
      maximum transported distance as a worst case scenario, and, hence, the potential
      health impact.

PMID- 19837478
TI  - Detection of protein on BTLAlow cells and in vivo antibody-mediated down
      modulation of BTLA on lymphoid and myeloid cells of C57BL/6 and BALB/c BTLA
      allelic variants.
AB  - B- and T-lymphocyte attenuator (BTLA, CD272) is a polymorphic molecule belonging
      to the Ig superfamily (SF) that attenuates BCR and TCR-mediated signaling, and
      thereby functions as a negative regulator of lymphocyte activation. Herein, we
      report an anti-murine BTLA mAb (clone 4G12b) that remarkably detects protein
      expression on BTLA(low) cells such as naive CD4(+) cells, CD8(+) T cells,
      dendritic cells (DC), as well as in NKT cells and for the first time, we found
      BTLA expression on DX5(dim) and DX5(bright) subsets of non-T NK cells in both
      C57BL/6 (B6) and BALB/c BTLA allelic variants. Anti-BTLA 4G12b mAb binds to an
      overlapping epitope to that recognized by anti-BTLA 6A6 mAb, but in contrast to
      the concept widely accepted of blocking activity of 6A6 mAb, surprisingly neither
      4G12b nor 6A6 mAbs impeded murine HVEM-mIgG(2a).Fc recombinant fusion protein
      from interacting with BTLA-expressing cells. Lastly, in vivo administration of
      anti-BTLA 4G12b mAb induced a profound and lasting down-modulation of BTLA
      expression that led to BTLA receptor internalization with the potential utility
      of shutting down BTLA expression at any stage during the course of the immune
      response in both B6 and BALB/c strains of mice.

PMID- 19837479
TI  - Outside the box and into thick air: implementation of an exterior mobile
      pediatric emergency response team for North American H1N1 (swine) influenza virus
      in Houston, Texas.
AB  - STUDY OBJECTIVE: We describe the implementation of a mobile pediatric emergency
      response team for mildly ill children with influenza-like illnesses during the
      H1N1 swine influenza outbreak. METHODS: This was a descriptive quality
      improvement study conducted in the Texas Children's Hospital (Houston, TX)
      pediatric emergency department (ED), covered, open-air parking lot from May 1,
      2009, to May 7, 2009. Children aged 18 years or younger were screened for viral
      respiratory symptoms and sent to designated areas of the ED according to level of
      acuity, possibility of influenza-like illness, and the anticipated need for
      laboratory evaluation. RESULTS: The mobile pediatric emergency response team
      experienced 18% of the total ED volume, or a median of 48 patients daily, peaking
      at 83 patients treated on May 3, 2009. Although few children had positive rapid
      influenza assay results and the morbidity of disease in the community appeared to
      be minimal for the majority of children, anxiety about pandemic influenza drove a
      large number of ED visits, necessitating an increase in surge capacity. Surge
      capacity was augmented both through utilization of existing institutional
      resources and by creating a novel area in which to treat patients with potential
      airborne pathogens. Infection control procedures and patient safety were also
      maximized through patient cohorting and adaptation of social distancing measures
      to the ED setting. CONCLUSION: The mobile pediatric emergency response team and
      screening and triage algorithms were able to safely and effectively identify a
      group of low-acuity patients who could be rapidly evaluated and discharged,
      alleviating ED volume and potentially preventing transmission of H1N1 influenza.

PMID- 19837480
TI  - Surveillance of catheter-associated urinary tract infection in 4 intensive care
      units at Alexandria university hospitals in Egypt.
AB  - BACKGROUND: We sought to measure the incidence rate of catheter-associated
      urinary tract infections (CAUTIs), identify risk factors associated with
      acquiring the infections; and identify the etiologic and antibiotic resistant
      patterns associated with CAUTIs in the intensive care units (ICUs) of a large
      University Hospital in Alexandria, Egypt. METHODS: Prospective active
      surveillance of CAUTIs was conducted in 4 ICUs during a 13-month period from
      January 1, 2007 through January 31, 2008 in Alexandria University Hospital using
      the standard Centers for Disease Control National Nosocomial Infection
      Surveillance (NNIS) case definitions. Rates were expressed as the number of
      infections per 1000 catheter days. RESULTS: During the study period, 757 patients
      were monitored after ICU admission, with either existing indwelling urinary
      catheters (239), or got catheters inserted after ICU admission (518), for a total
      duration of 16301 patient days, and 10260 patient catheter days. A total of 161
      episodes of infection were diagnosed, for an overall rate of 15.7 CAUTIs per 1000
      catheter days. Important risk factors associated with acquiring CAUTI were female
      gender (Relative risk (RR), 1.7; 95% confidence interval (CI); 1.7-4.3), and
      previous catheterization within the same hospital admission (RR, 1.6; 95% CI; 1.3
      1.96). Patients admitted to the chest unit, patients =40 years, patients with
      prolonged duration of catheterization, prolonged hospital and ICU stay had a
      significantly higher risk of acquiring CAUTIs. Out of 195 patients who had their
      urine cultured, 188 pathogens were identified for 161 infected patients; 96 (51%)
      were Candida, 63 (33.5%) gram negatives, 29 (15.4%) gram positives. The
      prevalence of ESBL producers among K. pneumoniae and E. coli isolates was 56%
      (14/25) and 78.6% (11/14), respectively. CONCLUSION: Despite infection control
      policies and procedures, CAUTI rates remain a significant problem in Alexandria
      University hospital. Using the identified risk factors, tailored intervention
      strategies are now being implemented to reduce the rates of CAUTIs in these 4
      ICUs.

PMID- 19837481
TI  - [Utility of plasmapheresis in intensive care].
AB  - We discuss the plasmapheresis (PE) carried out in an 18-bed polyvalent intensive
      care unit between the years 2003-2007. This article aims to report our experience
      in plasmapheresis performed with specific monitors for continuous renal
      replacement therapy (CRRT) that shows the versatility of the use of these
      procedures in intensive care. The utility of these procedures include many
      different critical disease settings in our units (neurology, hematology, and
      rheumatology patients). In short, our experience in PE has led us to the
      conclusion that plasmapheresis is a simple extracorporeal depuration treatment
      that can be performed by staff trained in intensive care at any moment within a
      wide spectrum of clinical indications, with CRRT monitors and with minimum
      adverse effects.

PMID- 19837482
TI  - Diagnosis, management and treatment of chronic Chagas' gastrointestinal disease
      in areas where Trypanosoma cruzi infection is not endemic.

PMID- 19837483
TI  - [Grieving among relatives and caregivers].
AB  - This article provides a definition and description of grief, its characteristics,
      and the current explanatory models of this phenomenon (the stage model, task
      model, constructivist model and dual process model). The authors argue that a
      state of mourning in advance is produced in the process of dementia as a result
      of significant relational loss before death and describe the risk factors for
      complicated grief in caregivers: overload, lack of personal and material
      resources, delegation of care, and complex feelings such as guilt. The need for
      healthcare organizations to provide professional caregivers with the appropriate
      means to help with grief and to develop their own measures to prevent burnout is
      stressed. These measures could include protocols that provide bereavement
      intervention with the family, the primary caregiver, other patients and/or
      residents and the professional caregiving team. Finally, losses in persons with
      dementia must be taken into consideration, avoiding phenomena such as silencing
      and overprotection and encouraging acceptance and emotional support of their pain
      so that organic and emotional complications do not occur.

PMID- 19837484
TI  - [Psychiatric commitments. Medicolegal aspects].
AB  - Compulsory hospitalization of mentally ill patients in a psychiatric center is a
      controversial issue due to the problems affecting their management, mainly
      coordination between health services and the police forces. This subject has been
      reviewed with major focus on Spanish Law, and also the medicolegal aspects the
      health professionals have to cope with. We can distinguish two types of
      psychiatric admissions considering the consent of the patient: a) voluntary or b)
      compulsory hospitalization. The Spanish Law "Ley 1/2000 de Enjuiciamiento Civil",
      explains the procedure on the involuntary admission of mentally ill patients.

PMID- 19837485
TI  - [Evaluation by "statistical parametric mapping" of the cerebral perfusion changes
      in patients with carotid artery stenosis after endarterectomy].
AB  - The efficacy of carotid endartectomy (CE) in cerebrovascular accidents produced
      by carotid stenosis can be evaluated with the cerebral perfusion with single
      photon emission tomography, using statistical parametric mapping (SPM). MATERIAL
      AND METHODS: Twelve patients with significant carotid stenosis who underwent
      endartectomy were included in the study. All underwent a cerebral perfusion study
      with 99mTc-etilen cisteinato dietilester (ECD) at baseline and after the
      endartectomy. Using SPM, the baseline/post-surgery study was compared
      independently with the control group made up of 20 patients and the corresponding
      parametric statistical mappings were obtained. Changes in extension (k(E) or
      voxel number) and intensity (change in the T value) of the significantly
      hypoperfused zones and direction of these changes were evaluated. RESULTS: In the
      group of 12 patients, improvement of the post-surgical cerebral perfusion was
      observed in 5 patients with an average 50.56% decrease in the extension of the
      hypoperfused zones and average 30.9% decrease of intensity. Four patients showed
      an average 85.53% increase in the extension of cerebral hypoperfusion and of
      34.21% in intensity. No significant changes between both studies were found in
      three patients. CONCLUSIONS: SPM has been shown to be a useful tool that makes it
      possible to objectify the cerebral brain flow changes produced after the surgical
      intervention, evaluating the changes in extension and intensity of the
      significantly hypoperfused zones.

PMID- 19837486
TI  - [Bone scintigraphy and scintigraphy with (111)In-octreotide in the diagnosis of
      bone metastasis of bronchial carcinoid tumor].

PMID- 19837487
TI  - Synthesis and antimicrobial activity of 7-(2-substituted phenylthiazolidinyl)
      benzopyran-2-one derivatives.
AB  - A series of 7-(2-substituted phenylthiazolidinyl)-benzopyran-2-one derivatives
      have been synthesized by reaction of 7-amino-4-methyl-benzopyran-2-one (1) with
      an appropriate substituted aldehydes to obtain various Schiff bases (3a-k) which
      on treatment with thioglycolic acid afforded the title compounds (4a-k). Purity
      of the compounds has been confirmed by TLC. Structure of these compounds were
      established on the bases IR, 1H NMR, 13C NMR and Mass spectral data. Schiff bases
      and title compounds were evaluated for antibacterial and antifungal activities
      against various bacterial and fungal strains. The results showed that compounds
      3d, 3f, 4d, 4f and 4i (100 microg/ml) exhibited good antibacterial and antifungal
      activity as that of standard antibiotics Ciprofloxacin and Griseofulvin.

PMID- 19837488
TI  - Application of genetic algorithm-support vector machine (GA-SVM) for prediction
      of BK-channels activity.
AB  - The support vector machine (SVM), which is a novel algorithm from the machine
      learning community, was used to develop quantitative structure-activity
      relationship (QSAR) for BK-channel activators. The data set was divided into 57
      molecules of training and 14 molecules of test sets. A large number of
      descriptors were calculated and genetic algorithm (GA) was used to select
      variables that resulted in the best-fitted for models. A comparison between the
      obtained results using SVM with those of multi-parameter linear regression (MLR)
      revealed that SVM model was much better than MLR model. The improvements are due
      to the fact that the activity of the compounds demonstrates non-linear
      correlations with the selected descriptors. Also distances between Oxygen and
      Chlorine atoms, the mass, the van der Waals volume, the electronegativity, and
      the polarizability of the molecules are the main independent factors contributing
      to the BK-channels activity of the studied compounds.

PMID- 19837489
TI  - Anti-trypanosomatid benzofuroxans and deoxygenated analogues: synthesis using
      polymer-supported triphenylphosphine, biological evaluation and mechanism of
      action studies.
AB  - Hybrid vinylthio-, vinylsulfinyl-, vinylsulfonyl- and vinylketo-benzofuroxans
      developed as anti-trypanosomatid agents, against Trypanosoma cruzi and Leishmania
      spp., have showed low micromolar IC(50) values. The synthetic route to access to
      these derivatives was an efficient Wittig reaction performed in mild conditions
      with polymer-supported triphenylphosphine (PS-TPP). Additionally, the
      benzofurozan analogues, deoxygenated benzofuroxans, were prepared using PS-TPP as
      reductive reagent in excellent yields. The trypanosomicidal and leishmanocidal
      activities of the benzofuroxan derivatives were measured and also some aspects of
      their mechanism of action studied. In this sense, inhibition of mitochondrial
      dehydrogenases activities, production of intra-parasite free radicals and
      cruzipain inhibition were studied as biological target for the anti
      trypanosomatid identified compounds. The trypanosomicidal activity could be the
      result of both the parasite-mitochondrion function interference and production of
      oxidative stress into the parasite.

PMID- 19837490
TI  - Effects of powdered fertilized eggs on the stress response.
AB  - BACKGROUND & AIMS: Effects of nutritional supplements on psychological wellbeing
      receive increasing attention. This double-blind placebo-controlled study
      investigated effects of a four week intake of powder of fertilized eggs (Young
      Tissue Extract; YTE) in a laboratory protocol (Trier Social Stress Test; TSST).
      METHODS: Aside the laboratory stress test, we examined differential effects on
      subjects with high and low levels of chronic stress. Thus, subjects were further
      divided into two subgroups with scores for chronic stress scores below and above
      average, respectively. RESULTS: Compared to placebo, a four week intake of YTE
      did not result in superior effects on general wellbeing. However, beneficial
      effects of YTE were observed in subjects with enhanced levels of chronic stress.
      When compared to placebo these subjects showed an improvement of both the
      psychological and endocrine stress response. CONCLUSIONS: Group differences
      suggest that YTE selectively improves adaptation to acute stress by normalizing
      the endocrine and the subjective stress response. Subjects with less chronic
      stress also reported less subjective stress but did not show beneficial effects
      on the endocrine stress response.

PMID- 19837491
TI  - Review of the radial free flap: is it still evolving, or is it facing extinction?
      Part one: soft-tissue radial flap.
AB  - The versatile fasciocutaneous radial flap is robust and reliable, straightforward
      to harvest, and often produces a satisfactory reconstruction with relatively
      little long-term morbidity at the donor site. Many surgeons prefer to use a
      limited number of trusted flaps, and these qualities will ensure that in the
      intermediate future most surgical trainees will continue to be shown the
      fasciocutaneous radial flap as both the basic training flap and the established
      option for reconstruction. Evidence from observational clinical studies and one
      randomised clinical trial indicates that there is increasing support for the use
      of the evolutionary technique of suprafascial dissection to minimise morbidity at
      the donor site. The suprafascial donor site may be repaired with either a meshed
      or unmeshed partial-thickness skin graft, or a fenestrated full-thickness skin
      graft, with good rates of successful healing. The application of a negative
      pressure dressing to the wound seems to facilitate the healing of all types of
      skin graft. The subfascial donor site, however, remains more prone to
      complications. It may be helpful to position the donor site of the flap more
      proximally, but this has not been proven. These refinements probably produce the
      best outcomes that can currently be achieved, given the inherent flaws of the
      radial donor site.

PMID- 19837492
TI  - Post-traumatic orbital cellulitis.

PMID- 19837493
TI  - Identifying women requiring maternity high dependency care.
AB  - The prompt identification of clinical deterioration and referral for appropriate
      care are key issues in the management of women who become critically ill during
      pregnancy, labour and the postpartum period. The Intensive Care Society has
      developed designated levels of care in relation to adult patient care, which may
      not be appropriate for use in midwifery. Therefore, exploring the midwifery,
      nursing and medical literature related to levels of care and detection of
      clinical deterioration may highlight the need for these to be modified and
      adapted for the development of midwifery-specific levels of care that are
      appropriate for this cohort.

PMID- 19837494
TI  - Extent of corpectomy determines primary stability following isolated anterior
      reconstruction in a thoracolumbar fracture model.
AB  - BACKGROUND: Based on the development of minimal-invasive techniques and
      introduction of new implants enabling secure reconstruction an increasing number
      of patients are treated by isolated anterior column surgery. Most biomechanical
      studies dealing with thoracolumbar fracture models use worst-case scenarios of
      complete corpectomies to simulate vertebral body defects neglecting the influence
      of remaining cortical bone in partial corpus instability. Using a standardized
      partial and total corpectomy model we investigated the effect of the extent of
      corpectomy on stiffness in an anterior reconstruction model. METHODS: Twelve
      human thoracolumbar specimens (Th11-L3) were loaded in a spine simulator with
      pure moments in the three motion planes. Following intact testing partial corp-
      and discectomy and later complete corpectomy of L1 were performed. Defects were
      instrumented by vertebral body replacements and additional anterior plating
      systems bridging the defect from Th12 to L2. Intersegmental rotations were
      measured between Th12 and L2. FINDINGS: Significantly (P<0.05) increased range of
      motion was found in reconstructions of total compared to partial corpectomy.
      Total corpectomy reconstructions showed solely in lateral bending a significant
      reduction of range of motion compared to the intact state, while in axial
      rotation and flexion/extension it was significantly increased. Partial corpectomy
      reconstructions resulted in significantly reduced range of motion for lateral
      bending and flexion/extension compared to the intact specimen. INTERPRETATION:
      Isolated anterior reconstructions of the thoracolumbar spine revealed sufficient
      stiffness in the partial vertebral corpus defect. In contrast, total corpectomy
      did not show an adequate stiffness. Especially in regard to rotational stiffness
      additional posterior fixation has to be recommended.

PMID- 19837495
TI  - Effect of axial load on anterior tibial translation when transitioning from non
      weight bearing to weight bearing.
AB  - BACKGROUND: While the application of compressive joint loads and thigh muscle
      activity are associated with anterior tibial translation in vitro, less is known
      during early load acceptance in vivo. We investigated the effects of increasing
      axial loads on anterior tibial translation and thigh muscle activity in healthy
      knees during transition from non-weight bearing to early weight bearing. METHODS:
      Participants (11 males, 11 females) underwent 20%, 40%, and 60% body weight
      acceptance trials at 20 degrees knee flexion while electromagnetic sensors
      measured anterior tibial translation (mm), and surface electromyography recorded
      quadriceps and hamstring muscle onset times (ms) and amplitudes (% maximal
      voluntary isometric contraction). Repeated measures ANOVA compared values across
      loads. Pearson correlations examined relationships between anterior tibial
      translation and muscle onset times and amplitudes within each load. FINDINGS: As
      load increased, anterior tibial translation (Mean (standard deviation)) (20%=4.7
      (1.7) mm<40%=7.1 (1.9) mm<60%=8.8 (2.1) mm), and quadriceps (20%=23.6 (14.9)%
      maximal voluntary isometric contraction <40%=32.7 (11.8)% maximal voluntary
      isometric contraction <60%=41.1 (13.5)% maximal voluntary isometric contraction)
      and hamstring (20%=15.5 (15.7)% maximal voluntary isometric contraction <40%=23.0
      (16.4)% maximal voluntary isometric contraction <60%=27.6 (19.1)% maximal
      voluntary isometric contraction) activation increased, while quadriceps (20%=96.7
      (28.4) ms>60% 80.2 (21.8) ms) and hamstring (20%=141.5 (65.0) ms and 40%=126.3
      (68.8)>60% 107.6 (28.4) ms) onset times decreased (P0.05). There were no
      relationships between anterior tibial translation and muscle activation
      amplitudes (R=0.033-0.294) or onset times (R=-0.031-0.374) (P>0.09).
      INTERPRETATION: Greater axial loads near full knee extension during early weight
      acceptance result in greater anterior tibial translation, regardless of faster
      and stronger activation amplitudes. These findings support injury prevention
      programs aimed to reduce impact forces as they may in turn reduce anterior tibial
      translation and corresponding ligamentous strain during dynamic activity.

PMID- 19837496
TI  - Biomechanical evaluation of a new reconstruction technique of the ulnar
      collateral ligament in the elbow with modified bone tunnel placement and
      interference screw fixation.
AB  - BACKGROUND: A new method for reconstruction of the anterior bundle of the ulnar
      collateral ligament using modified bone tunnel placement and interference screw
      fixation was developed to minimize operative dissection, improve graft
      tensioning, and reduce associated operative morbidities. The objective of this
      study was to compare varus-valgus laxity and failure properties of this new ulnar
      collateral ligament reconstruction to the intact ulnar collateral ligament.
      METHODS: Nine matched pairs of cadaveric upper extremities were used, the intact
      ulnar collateral ligament as the control for the load to failure properties and
      the contralateral arm for ulnar collateral ligament reconstruction. Varus-valgus
      laxity was measured at 30 degrees, 50 degrees, 70 degrees, and 90 degrees of
      elbow flexion for intact, ulnar collateral ligament transected, and ulnar
      collateral ligament reconstruction. Ulnar collateral ligament reconstruction was
      performed using a tendon graft passed through a bone tunnel and looped around the
      medial column of the humerus without dissection of the ulnar nerve. Distally, the
      graft was looped through a bone tunnel in the proximal ulna. Both ends were
      secured with interference screws. The specimens were loaded to failure at 50
      degrees of flexion at a rate of 30 deg/s. Repeated measures analysis of variance
      with a P value of 0.05 was used. FINDINGS: Elbow laxity significantly increased
      with ulnar collateral ligament transection. Following reconstruction, varus
      valgus laxity at 30 degrees and 50 degrees of elbow flexion was completely
      restored to the intact state, only partially restored at 70 degrees, and not
      changed at 90 degrees. There was no significant difference between the yield and
      ultimate torques for the intact vs. reconstructed elbows. The angular
      displacement at yield and failure was significantly greater for the reconstructed
      elbows compared to the intact. INTERPRETATION: This reconstruction technique
      provides comparable strength to that of the native ligament. While stability was
      improved, failure occurred at greater angular displacement for the reconstructed
      limbs.

PMID- 19837497
TI  - The role of therapist self-disclosure in psychotherapy: a qualitative review.
AB  - Over 90% of therapists self-disclose to clients (Mathews, 1989; Pope, Tabachnick,
      & Keith-Spiegel, 1987; Edwards & Murdock, 1994), however, the implications of
      therapist self-disclosure are unclear, with highly divergent results from one
      study to the next. The goal of this paper was to review the empirical literature
      relevant to therapist self-disclosure, and provide the reader with a
      comprehensive understanding of the factors that affect, and are affected by,
      therapist self-disclosure. Findings are organized into an integrated model
      examining the who, what, when, why, and how of therapist self-disclosure. In
      addition, training implications and suggestions for future research are provided.

PMID- 19837498
TI  - Hastening death in end-of-life care: a survey of doctors.
AB  - The application of medical technology to prolong life at the expense of quality
      of life is widely debated in end-of-life care. A national survey of 3733 UK
      doctors reporting on the care of 2923 people who had died under their care is
      reported here. Results show that there was no time to make an 'end-of-life
      decision' (deciding to provide, withdraw or withhold treatment) for 8.5% of those
      reporting deaths. A further 55.2% reported decisions which they estimated would
      not hasten death and 28.9% reported decisions they had expected to hasten death.
      A further 7.4% reported deaths where they had to some degree intended to hasten
      death. Where patients or someone else had made a request for a hastened death,
      doctors were more likely to report expecting or at least partly intending to
      hasten death. Doctors usually made these decisions in consultation with
      colleagues, relatives and, where feasible, with patients. Intensive care
      specialists were particularly likely to report a degree of intention to hasten
      the end of life and to have treated patients lacking the capacity to discuss
      these decisions. Palliative medicine specialists were the least likely to report
      decisions they expected or at least partly intended to end life, in spite of
      reporting a high incidence of requests from their patients for a hastened death.
      Doctors with strong religious beliefs or who opposed the legalisation of assisted
      dying were unlikely to report such decisions. Elderly women and those with
      dementia are groups considered vulnerable in societies where a permissive
      approach is taken to hastening death in end-of-life care, but doctors describing
      these deaths were no more likely to report decisions which they expected or at
      least partly intended to end life. The survey suggests that concerns about the
      sanctity of life, as well as estimates of the quality of life, enter clinical
      decision-making.

PMID- 19837499
TI  - The role of the extended family in women's risk of intimate partner violence in
      Jordan.
AB  - The extended family as a potential cause of and protection against intimate
      partner violence (IPV) remains relatively unstudied. This mixed-methods study
      used focus group discussions (FGDs) and a clinic-based survey to investigate
      several family-based risk and protective factors associated with women's risk of
      IPV in Jordan. Seventeen FGDs (total number of participants = 105) were conducted
      with women in Amman. Each transcript was coded for categories using open coding
      methodology and mapping. Relevant categories and subcategories were family
      support, family interference, family abuse, exposure to violence in childhood,
      and place of residence. For the survey, systematic probability proportionate to
      size methodology was used to select a sample of 517 literate, ever married, women
      from seven reproductive health clinics located throughout the country (response
      rate = < or = 70%); due to missing data, the analytic sample was restricted to
      418 women. Measures assessed the categories mentioned above. Bivariate and
      multivariate logistic regression models were constructed to examine the
      relationship between IPV and the main predictors of interest (residence, family
      interference, family violence, exposure to violence as a child, and family
      support). The combined results of the FGDs and the survey demonstrated that the
      respondent's husband's exposure to violence in childhood and violence perpetrated
      by other family members were risk factors for IPV. Family interference was also
      significantly related to IPV but only when the respondent identified the
      interference as harmful to her relationship. Residence with the respondent's in
      laws demonstrated mixed effects. A supportive family was protective against IPV,
      although the FGDs revealed that families were not always an effective source of
      assistance. Findings demonstrate the continued role of the wife's and husband's
      kin in women's risk of IPV in Jordan, highlighting the importance of a broader
      view of the context of IPV.

PMID- 19837500
TI  - The right parahippocampal gyrus contributes to the formation and maintenance of
      bound information in working memory.
AB  - Working memory is devoted to the temporary storage and on-line manipulation of
      information. Recently, an integrative system termed the episodic buffer has been
      proposed to integrate and hold information being entered or retrieved from
      episodic memory. Although the brain system supporting such an integrative buffer
      is still in debate, the medial temporal lobe appears to be a promising candidate
      for the maintenance of bound information. In the current work, binding was
      assessed by comparing two conditions in which participants had to retain three
      letters and three spatial locations presented either bound or separate. At the
      behavioral level, lower performance was found for bound information than for
      separate information. When contrasting the two conditions, activation in the
      right parahippocampal gyrus was greater for the encoding and maintenance of bound
      information. No activation was observed in the medial temporal lobe during the
      retrieval of bound information. Together, our results suggest that the
      parahippocampal gyrus may underlie the integrative and maintenance functions of
      the episodic buffer.

PMID- 19837501
TI  - Injuries occurring in hospital staff attending medical emergency team (MET) calls
      -a prospective, observational study.
AB  - BACKGROUND: Clinical emergency response systems such as medical emergency teams
      (MET) have been implemented in many hospitals worldwide, but the effect that
      these systems have on injuries to hospital staff is unknown. The objective of
      this study was to determine the rate and nature of injuries occurring in hospital
      staff attending MET calls. METHODS: This study was a prospective, observational
      study, using a structured interview, of 1265 MET call participants, in a 650 bed
      urban, teaching hospital. Data was collected on the number and the nature of
      injuries occurring in hospital staff attending MET calls. RESULTS: Over 131 days,
      248 MET calls were made. An average of 8.1 staff participated in each MET call.
      The overall injury rate was 13 (95% confidence interval (CI) 7-20) per 1000 MET
      participant attendances, and 70 (95% CI 38-102) per 1000 MET calls. One injured
      participant required time off-work, an injury requiring time off-work rate of 1
      (95% CI 0-4) per 1000 MET participant attendances, or 4 (95% CI 0-27) per 1000
      MET calls. The relative risk of sustaining an injury if the MET participant
      performed chest compressions, contacted patient body fluids on clothing or
      protective equipment, without direct contact to skin or mucosa, or lifted the
      patient or a patient body part was 11.0 (95% CI 4.2-28.6), 8.7 (95% CI 3.4-22.0)
      and 5.5 (95% CI 2.1-14.2), respectively. CONCLUSION: The rate of injuries
      occurring to hospital staff attending MET calls is relatively low, and many
      injuries could be considered relatively minor.

PMID- 19837502
TI  - The guidelines got it right on defibrillation energy protocol.

PMID- 19837503
TI  - Perineal trauma following operative vaginal delivery without episiotomy.

PMID- 19837504
TI  - A new kinetic model for biochemical oscillations: graph-theoretical analysis.
AB  - A graphical analysis demonstrates the ability of slow substrate activation and
      certain types of cooperativity between the two enzyme active sites to generate
      sustained oscillations. The analysis allows us to estimate kinetic parameter
      values for which oscillations exist. The scheme analyzed can explain the cyclical
      changes in functioning of various motor enzymes. Moreover, this scheme does not
      generate bistability for any parameter values. The graphical analysis presented
      is simple and visually clarifies the regulatory role of the details in the
      kinetic schemes.

PMID- 19837505
TI  - Cost-benefit analysis of central softening for production of drinking water.
AB  - Softening drinking water before distribution yields advantages with environmental
      impact, such as lower household products consumption, less scaling in piping and
      machines, and the avoidance of decentralized, domestic softeners. Central
      softening is under consideration in Flanders by the largest water supplier, VMW
      (Dutch acronym for "Flemish Company for Water Supply"), to deliver soft (15
      degrees F) water to their customers. A case study is presented for a region with
      hard water (47 degrees F). The chosen technique is the pellet reactor, based on
      precipitation of CaCO(3) by NaOH addition. This softening operation has possibly
      large impact on the environment and the water consumption pattern. A cost-benefit
      analysis has been made to estimate the added value of central softening, by
      investigating the impact on the drinking water company, on their customers, on
      employment, on environment, on health, etc. The analysis for the region of study
      revealed benefits for customers which were higher than the costs for the drinking
      water company. However, pricing of drinking water remains an important problem. A
      sensitivity analysis of these results has also been made, to evaluate the impact
      of important hypothesis, and to be able to expand this study to other regions.
      The conclusions for this part show that softening is beneficial if water hardness
      is to be decreased by at least 5 degrees F.

PMID- 19837507
TI  - Re: Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, et al. Stage pT0 in
      radical prostatectomy with no residual carcinoma and with a previous positive
      biopsy conveys a wrong message to clinicians and patients: why is cancer not
      present in the radical prostatectomy specimen? Eur Urol 2009;56:272-4.

PMID- 19837508
TI  - Epidural hematoma revealed by exophthalmia, two cases reports.
AB  - Epidural or extradural hematoma is a well known entity, usually a complication of
      severe traumatic head injury. The clinical presentation is most commonly a
      decline in consciousness and new neurological deficits. Fewer than 20% of
      patients demonstrate the classic presentation of a lucid interval between the
      initial trauma and subsequent neurological deterioration. The association of an
      epidural hematoma with a subperiostal intraorbital hematoma is rare, where
      exophthalmia is the only presenting sign. We report on two cases of frontal
      epidural hematoma revealed by an exophthalmia after a minor head trauma. On
      reporting our cases we aim to increase the awareness of this association each
      time a head or facial trauma is associated with exophthalmia.

PMID- 19837509
TI  - Modafinil for multiple sclerosis fatigue: does it work?
AB  - Modafinil is sometimes used in the clinical setting for treating multiple
      sclerosis (MS) fatigue, despite conflicting and disappointing results from
      clinical trials. OBJECTIVE: We audited the patient perceived effectiveness of
      modafinil when used in clinical practice in a carefully selected group of
      patients with typical MS fatigue. METHODS: All MS patients commenced on modafinil
      for fatigue in the Oxford MS clinic were identified retrospectively, and the
      patient perceived benefit, side effects and decision on continuation of therapy
      at 1 month was obtained from the medical notes. Additionally all patients were
      subsequently interviewed, up to 5 years after treatment initiation. RESULTS:
      Surprisingly, 69% patients with fatigue also suffered excessive daytime
      sleepiness, and this subgroup found modafinil more beneficial. There was a better
      response against excessive daytime sleepiness than fatigue. The benefit against
      fatigue or sleepiness was generally sustained (median 1 year). CONCLUSION: This
      suggests that modafinil may be useful, particularly when MS fatigue is associated
      with sleepiness. The relationship between fatigue and excessive daytime
      sleepiness is poorly understood and needs to be better defined before appropriate
      measures of the most clinically relevant outcomes can be selected for clinical
      trials. Outcome measures used in previous clinical trials have not properly
      evaluated the effects of modafinil.

PMID- 19837510
TI  - The activity and characterization of CeO2-TiO2 catalysts prepared by the sol-gel
      method for selective catalytic reduction of NO with NH3.
AB  - A series of Ce-Ti mixed-oxide catalysts were prepared by the sol-gel method for
      selective catalytic reduction (SCR) of NO with ammonia as reductant. These
      catalysts were characterized by XRD, BET, and XPS techniques. The experimental
      results show that the best Ce-Ti mixed-oxide catalyst yielded 98.6% NO
      conversion, and 100% N(2) selectivity at typical SCR reaction temperatures (300
      400 degrees C) and the high gas hourly space velocity of 50,000 h(-1). As the Ce
      loading (the mass ratio of CeO(2)/TiO(2)) was increased from 0 to 0.6, NO
      conversion increased markedly, but decreased at higher Ce loading. The most
      active catalyst was obtained with a Ce loading of 0.6. The high activity might be
      attributed to high Ce loading, strong interaction between Ce and Ti, high
      concentration of amorphous Ce on the catalyst surface, or the increase of
      chemisorbed oxygen or/and weakly bonded oxygen species, resulting from the
      presence of Ce(3+) after Ce addition. The effect of the calcination temperature
      was also investigated, and the optimal calcination temperature was 500 degrees C.
      The presence of oxygen played an essential role in NO reduction, and the activity
      of the Ce(0.6)Ti catalyst was not depressed when oxygen concentration was higher
      than 1%. The effect of SO(2) and H(2)O on the activity of the Ce(0.6)Ti catalyst
      was bound up with the reaction temperature.

PMID- 19837511
TI  - Assessment of heavy metal contamination in soils at Jajmau (Kanpur) and Unnao
      industrial areas of the Ganga Plain, Uttar Pradesh, India.
AB  - Environmental geochemical studies were carried out in and around Jajmau (Kanpur)
      and Unnao industrial areas (80 degrees 15'-80 degrees 34'E longitude and 26
      degrees 24'-26 degrees 35'N latitude), of Uttar Pradesh to find out the extent of
      chemical pollution in soil due to industrial waste. Jajmau and Unnao are
      prominent centers for leather processing clusters of tannery industries (about
      450) along the banks of river Ganga, besides other industries. Geologically the
      study area is beset with alluvium of Quaternary age consisting of older alluvium
      of middle to upper Pleistocene and newer alluvium of Holocene. The climate of the
      study area is semi-arid type. Fifty-three soil samples were collected from Jajmau
      and Unnao industrial areas from top 15 cm layer of the soil and were analyzed for
      heavy metals by using Philips MagiX PRO-PW 2440 X-ray fluorescence spectrometer.
      The data reveals that the soil in the area is significantly contaminated with
      heavy metals such as chromium varies from 161.8 to 6227.8 mg/kg (average of
      2652.3mg/kg), Ba varies from 44.1 to 780.9 mg/kg (average of 295.7 mg/kg), Cu
      varies from 1.7 to 126.1mg/kg (average of 42.9 mg/kg), Pb varies from 10.1 to
      67.8 mg/kg (average of 38.3mg/kg), Sr varies from 46.6 to 150.6 mg/kg (average of
      105.3mg/kg), V varies from 1.3 to 208.6 mg/kg (average of 54.4 mg/kg) and Zn
      varies from 43.5 to 687.6 mg/kg (average of 159.9 mg/kg). Soil contamination was
      assessed on the basis of geoaccumulation index, enrichment factor (EF),
      contamination factor and degree of contamination. Indiscriminate dumping of
      hazardous waste in the study area could be the main cause of the soil
      contamination, spreading by rainwater and wind. Distribution and correlation of
      heavy metals in soil along with possible remedial measures are discussed.

PMID- 19837512
TI  - Evidence of descending inhibition deficits in atypical but not classical
      trigeminal neuralgia.
AB  - Trigeminal neuralgia (TN) is a rare neuropathic facial pain disorder. Two forms
      of TN, classical TN (CTN) and atypical TN (ATN), are reported and probably have
      different aetiologies. The aim of the present study was to evaluate the
      functional integrity of the diffuse noxious inhibitory controls (DNIC) in (1) a
      group of patients with classical trigeminal neuralgia (CTN), (2) a group of
      patients with atypical trigeminal neuralgia (ATN), and (3) a group of healthy
      controls in order to determine if a descending pain modulation deficit could
      participate in the pathophysiology of TN pain. DNIC responses of 14 CTN patients,
      14 ATN patients and 14 healthy controls were obtained by comparing thermode
      induced facial heat pain scores before and after activating DNIC. DNIC was
      triggered using a standard counter-irritation paradigm (i.e., immersion of the
      arm in painfully cold water). General sensitivity to pain was also evaluated by
      measuring mechanical pain thresholds over 18 points located outside the
      trigeminal territory. Healthy participants and CTN patients showed a 21% and 16%
      reduction in thermode-induced pain following the immersion, respectively (all p
      values <.01), whereas ATN patients experienced no change (p=.57). ATN patients
      also had more tender points (mechanical pain thresholds<4.0kg) than CTN and
      healthy controls (all p-values <.05). Taken together, these results suggest that
      the underlying physiopathology differs between CTN and ATN and that a deficit in
      descending inhibition may further contribute to the pain experienced by patients
      with ATN.

PMID- 19837513
TI  - Genetic factors of sheep affecting gastrointestinal parasite infections in the
      Distrito Federal, Brazil.
AB  - Three sheep farms were used in the Distrito Federal, Central Brazil, to study the
      occurrence of parasites in the feces. A total of 1798 collections were taken over
      the period of a year. A total of 1205 were taken in Santa Ines breed (SI) in all
      three farms, 323 in Bergamasca (Berg), 54 in Ile de France, 49 in IlexSI, 103 in
      Morada Nova (MN) and 64 in TexelxSI, these last five groups being on a single
      farm. The animals were drenched soon after weaning and feces collected every 3
      weeks to calculate fecal egg count (FEC), at least on two occasions on each
      animal. In some cases, blood was collected to determine packed cell volume (PCV)
      at fecal collection. Fixed effects included farm, breed/genetic group within
      farm, animal age (months), birth type (simple, twin) and sex. (Co)variance
      components were estimated for Santa Ines sheep using restricted maximum
      likelihood under an animal model. FECs were affected by month and farm showing
      that climate and management are important sources of variation for the parasites
      studied. While age and birth type of the lambs did not affect infection level,
      their genetic group was important, showing that breeding strategies can help
      control these parasites. Heritabilities for infection level in the sheep varied
      between 0.09 for Strongyloides and 0.31 for Moniezia expansa. Genetic selection
      strategies for sheep aimed at reducing these infections should result in more
      resistant animals.

PMID- 19837514
TI  - Genotypic diversity, a survival strategy for the apicomplexan parasite Theileria
      parva.
AB  - The tick-borne protozoan parasite Theileria parva causes East Coast fever (ECF),
      a severe lymphoproliferative disease of cattle that is a major constraint to the
      improvement of livestock in eastern, central and southern Africa. Studies in
      cattle experimentally infected with T. parva have shown that the protective
      cytotoxic T lymphocyte (CTL) response is tightly focused, with individual animals
      recognizing only one or two dominant antigens, the identity of which varies with
      MHC class I phenotype. It is well known that cross-protection between T. parva
      stocks is limited, but precise evaluation of genetic diversity in field
      populations of the parasite has been hampered by a lack of molecular markers
      spanning the genome. A recently described panel of satellite markers has provided
      evidence for substantial genotypic diversity and recombination but does not
      provide cover for large segments of the genome. To address this deficiency, we
      undertook to identify additional polymorphic markers covering these regions and
      we report herein 42 newly identified PCR-RFLP markers distributed across the 4 T.
      parva chromosomes, as well as 19 new satellite markers for chromosomes 1 and 2.
      This brings the total number of available polymorphic markers to 141 for the 8.5
      Mb genome. We have used these markers to characterise existing parasite
      stabilates and have also shown that passage of the parasite through naive cattle
      and ticks can lead to substantial changes of parasite populations in resulting
      stabilates. These markers have also been used to show that passage of mixed
      parasites through an immunised calf results in the removal of the immunising
      genotype from the parasite population produced by ticks fed on this animal.

PMID- 19837515
TI  - Babesia canis and other tick-borne infections in dogs in Central Poland.
AB  - Vector-borne infections constitute increasing health problem in dogs worldwide,
      including sled dogs, dramatically decreasing the fitness of working dogs and even
      leading to death. In the period 2006-2008 eighty-two blood samples were collected
      from eight sled dog kennels in Central Poland. The prevalence of four vector
      borne infections (Babesia canis, Bartonella sp., Anaplasma/Ehrlichia and Borrelia
      burgdorferi) was estimated in 82 sled dogs using PCR and nested PCR for diagnosis
      and the same methods were used to identify the vector-borne pathogens in 26 dogs
      presenting at veterinary clinics with symptoms of vector-borne diseases. None of
      four studied vector-borne pathogens was detected in samples originating from
      veterinary clinics. Among the remaining 82 dogs B. canis infections were
      confirmed in three dogs undergoing treatment for babesiosis. The DNA of tick
      borne pathogens was also found among 22 (27.8%) of the 79 apparently healthy
      dogs, including 20 cases of B. canis infection (25.3%), one case of B.
      burgdorferi s.l. infection and one case of Anaplasma phagocytophilum infection.
      No evidence of Bartonella spp. and Ehrlichia canis infections were found in this
      set of samples. Sequencing of a Babesia fragment of 18S rDNA amplified from acute
      (n=5) and asymptomatic (n=5) cases revealed that all isolates were identical to
      the Babesia canis canis sequence, originally isolated from Dermacentor
      reticulatus ticks in Poland. A range of factors was shown to affect the
      distribution of babesiosis in sled dogs. The data are also discussed in respect
      to the health risk factors generated by asymptomatic B. canis infections and the
      efficiency of chemoprophylaxis measures taken by sled dog owners.

PMID- 19837516
TI  - Transformation of Anaplasma marginale.
AB  - The tick-borne pathogen, Anaplasma marginale, has a complex life cycle involving
      ruminants and ixodid ticks. It causes bovine anaplasmosis, a disease with
      significant economic impact on cattle farming worldwide. The obligate
      intracellular growth requirement of the bacteria poses a challenging obstacle to
      their genetic manipulation, a problem shared with other prokaryotes in the genera
      Anaplasma, Ehrlichia, and Rickettsia. Following our successful transformation of
      the human anaplasmosis agent, A. phagocytophilum, we produced plasmid constructs
      (a transposon bearing plasmid, pHimarAm-trTurboGFP-SS, and a transposase
      expression plasmid, pET28Am-trA7) designed to mediate random insertion of the
      TurboGFP and spectinomycin/streptomycin resistance genes by the Himar1 allele A7
      into the A. marginale chromosome. In these trans constructs, expression of the
      fluorescent and the selectable markers on the transposon, and expression of the
      transposase are under control of the A. marginale tr promoter. Constructs were co
      electroporated into A. marginale St. Maries purified from tick cell culture, and
      bacteria incubated for 2 months under selection with a combination of
      spectinomycin and streptomycin. At that time, < or =1% of tick cells contained
      colonies of brightly fluorescent Anaplasma, which eventually increased to infect
      about 80-90% of the cells. Cloning of the insertion site in E. coli and DNA
      sequence analyses demonstrated insertion of the entire plasmid pHimarAm
      trTurboGFP-SS encoding the transposon in frame into the native tr region of A.
      marginale in an apparent single homologous crossover event not mediated by the
      transposase. Transformants are fastidious and require longer subculture intervals
      than wild type A. marginale. This result suggests that A. marginale, as well as
      possibly other species of Anaplasma and Ehrlichia, can be transformed using a
      strategy of homologous recombination.

PMID- 19837517
TI  - Borderline personality disorder: hypothalamus pituitary adrenal axis and findings
      from neuroimaging studies.
AB  - Borderline personality disorder (BPD) is a complex and serious mental disorder
      that is commonly seen psychiatric practice. Although stress, especially early
      life stress, seems to be associated with the development of the disorder, there
      has been far less research on the function of the hypothalamic-pituitary-adrenal
      (HPA) axis in BPD, compared to other psychiatric disorders, such as major
      depressive disorder and post-traumatic stress disorder. Stress has been suggested
      to exert damaging effects on the brain, particularly the hippocampus; therefore,
      neuroimaging studies yield important insight into the neurobiology of BPD. This
      article reviews research on the HPA axis and neuroimaging studies in BPD and aims
      to integrate these findings.

PMID- 19837519
TI  - Can 'ectopic pregnancy' become 'normal pregnancy'?

PMID- 19837520
TI  - [Validation of a French version of the short form of the Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12)].
AB  - INTRODUCTION: The aim of this paper was to report a linguistically validated
      French version of the PISQ-12. PATIENTS AND METHODS: French validated version of
      the PISQ-12 was developed after two independent translations (English-French),
      one back-translation (French-English), a review by two French clinicians skilled
      in urogynecology and a testing on a sample of patients with pelvic floor
      disorders. This linguistic validation process was conducted by Mapi Research
      Institute in collaboration with the author of the original version, R. Rogers,
      and sponsored by Coloplast. RESULTS: PISQ-12 is the short form of a reliable
      specific condition, originally developed and psychometrically validated in
      English, and a self-administrated instrument to evaluate sexual function in women
      with pelvic organ prolapse and/or urinary incontinence. The questionnaire
      contains 12 items divided into three domains, labelled behavioral/emotive,
      physical and partner-related. French linguistic validation does not consist in
      literally translating the original questionnaire but rather in developing
      conceptually equivalent and an easily understood version by French women.
      CONCLUSION: This tool is essential to assess the sexual impact of pelvic floor
      disorders and to better understand the consequences of their treatments on
      sexuality.

PMID- 19837518
TI  - Acute HPA axis response to naltrexone differs in female vs. male smokers.
AB  - BACKGROUND: Both opioid antagonist administration and cigarette smoking acutely
      increase hypothalamic-pituitary-adrenal (HPA) axis activity as measured by
      adrenocorticotropic hormone (ACTH) and cortisol levels. However, male and female
      smokers may differ in their response to the opioid antagonist naltrexone, which
      may be partially mediated by sex differences in HPA axis function. Smokers, as a
      group, have frequently been shown to have HPA axis dysfunction, which may have
      relevance to the course and maintenance of nicotine dependence. The purpose of
      this study was to examine possible sex differences in HPA axis function by
      comparing stress-hormone response to naltrexone within healthy male and female
      smokers. Additionally, exploratory analyses compared the combined effects of
      naltrexone and cigarette smoking on hormonal responsivity between the sexes.
      METHOD: Thirty-eight healthy smokers (22 men) were tested in two separate morning
      sessions after 12h of smoking abstinence. For women, self-reports of menstrual
      cycle information were obtained prior to each session (date of last menstruation,
      cycle length, reproductive phase, etc.). Each participant received 50mg
      naltrexone or placebo capsule (in random order) and plasma levels of ACTH and
      cortisol were assessed at regular intervals for several hours. A subgroup of 12
      participants underwent a similar, additional session in which they smoked a
      single cigarette three hours after naltrexone administration. RESULTS: Naltrexone
      significantly increased ACTH and cortisol levels in women, but not men
      (DrugxSexxTime, p<0.05). A post hoc analysis suggested that women at an estimated
      'high estrogen' phase had a greater cortisol response (DrugxEstrogen level,
      p<0.05) than those at an estimated 'low estrogen' phase. Exploratory analyses
      showed that smoking a single cigarette potentiated naltrexone-induced increases
      in ACTH (p<0.05) and cortisol (p<0.01) in all participants. CONCLUSION: The
      findings support the hypothesis that women are more sensitive to opioid
      antagonism at the level of the HPA axis. Although further studies are needed to
      examine mechanisms underlying these responses, both results may have clinical
      implications for the use of naltrexone as a treatment for nicotine dependence.

PMID- 19837521
TI  - Use of molecular and milk production information for the cost-effective diagnosis
      of bovine viral diarrhoea infection in New Zealand dairy cattle.
AB  - An increase in veterinary and farmer interest in bovine viral diarrhoea (BVD) in
      New Zealand over recent years led to requests for cost-effective identification
      of BVD virus (BVDV) infected herds and individuals. This study was undertaken to
      determine if the use of real-time reverse transcriptase polymerase chain reaction
      (RT-PCR) technology and dairy cow production data could identify persistently
      infected (PI) animals in milking herds. Milk samples were collected from the vats
      of dairy herds and tested for the presence of BVDV by RT-PCR till four herds were
      found containing PI animals. Individual serum samples were then collected from
      every cow in the herd and tested by both RT-PCR and antigen capture enzyme-linked
      immunosorbent assays (ACE) to identify the PI animals. Individual animal testing
      found 1/223, 1/130, 2/800 and 1/275 PI's respectively in the four herds. Based on
      these results a maximum pool size of 400 cows contributing to the bulk tank milk
      was selected. After removal of the PI from the herds, further bulk milk samples
      were shown to be BVDV negative by RT-PCR. All the PI animals identified by this
      method were found in the lowest producing 10-20% of herd. This approach of
      targeted testing of dairy herds using PCR technology, in conjunction with animal
      production information, markedly reduced the cost of diagnostic testing for BVDV
      in dairy herds in New Zealand. Questionnaire follow-up on 81 BVDV-positive herds
      (15% of those tested) indicated the stratification approach identified milking
      PIs successfully over 90% of the time and reduced the number of individual tests
      to 12% of the milking herd.

PMID- 19837522
TI  - Natural infection with canine distemper virus in hand-feeding Rhesus monkeys in
      China.
AB  - An outbreak of canine distemper virus (CDV) in hand-feeding Rhesus monkeys in
      China was reported. Twenty Rhesus monkeys presented blood and mucus in feces,
      respiratory symptoms, anorexia, acute fever, thicken of footpad and red rashes in
      the faces over 1-month period. CDV infection was identified by characteristic
      clinical signs, the specific detection of the BIT Rapid color CDV detection kit,
      electron microscopy and the results of sequence aligning. A phylogenetic analysis
      further confirmed that the CDV in the Rhesus monkeys belonged to the clade of the
      epidemic CDV types of China. All the infected monkeys were monitored and treated
      with antiserum therapy. The antiserum therapy seemed more effective for adult
      monkeys than young monkeys. Twelve monkeys died. The high mortality might
      indicate that the virulence of CDV to monkeys was enhanced. This is the first
      report we are aware of documenting Rhesus monkeys infected with CDV in China.
      Urgent work should be done to prevent the possibly epidemic of CDV in non-human
      primate.

PMID- 19837523
TI  - Detection of classical enterotoxins of Staphylococcus aureus strains isolated
      from bovine subclinical mastitis in Isfahan, Iran.

PMID- 19837524
TI  - Vitamin D insufficiency: a risk factor to vertebral fractures in community
      dwelling elderly women.
AB  - OBJECTIVE: To determine the risk factors for the presence of moderate/severe
      vertebral fracture, specifically 25-hydroxyvitamin D (25-OHD). STUDY DESIGN:
      Cross-sectional study conducted for 2 years in the city of Sao Paulo, Brazil
      including community-dwelling elderly women. METHODS: Bone mineral density (BMD),
      serum 25-OHD, intact parathyroid hormone (iPTH), calcium and estimated glomerular
      filtration rate (eGFR) were examined in 226 women without vertebral fractures (NO
      FRACTURE group) and 189 women with at least one moderate/severe vertebral
      fracture (FRACTURE group). Vertebral fracture assessment (VFA) was evaluated
      using both the Genant semiquantitative (SQ) approach and morphometry. RESULTS:
      Patients in the NO FRACTURE group had lower age, increased height, higher calcium
      intake, and higher BMD compared to those patients in the FRACTURE group (p<0.05).
      Of interest, serum levels of 25-OHD in the NO FRACTURE group were higher than
      those observed in the FRACTURE group (51.73 nmol/L vs. 42.31 nmol/L, p<0.001).
      Reinforcing this finding, vitamin D insufficiency (25-OHD<75 nmol/L) was observed
      less in the NO FRACTURE group (82.3% vs. 93.65%, p=0.001). After adjustment for
      significant variables within the patient population (age, height, race, calcium
      intake, 25-OHD, eGFR and sites BMD), the logistic-regression analyses revealed
      that age (OR=1.09, 95% CI 1.04-1.14, p<0.001) femoral neck BMD (OR=0.7, 95% CI
      0.6-0.82, p<0.001) and 25-OHD <75 nmol/L (OR=2.38, 95% CI 1.17-4.8, p=0.016)
      remains a significant factor for vertebral fracture. CONCLUSION: Vitamin D
      insufficiency is a contributing factor for moderate/severe vertebral fractures.
      This result emphasizes the importance of including this modifiable risk factor in
      the evaluation of elderly women.

PMID- 19837525
TI  - Interstitial cystitis/bladder pain syndrome: an update.
AB  - Interstitial cystitis, or painful bladder syndrome, is a condition characterized
      by bladder pain, urinary frequency, urgency, and nocturia. The cause of the
      condition remains obscure and it remains a diagnosis of exclusion. Current
      theories of pathogenesis include a chronic or subclinical infection,
      autoimmunity, neurogenic inflammation or bladder urothelial defects. The
      definitions and terminology have undergone several proposed changes in the last
      five years. The International Incontinence Society (ICS) provided a revised
      definition of painful bladder syndrome (PBS) in 2002. The European Society for
      the Study of Interstitial Cystitis (ESSIC) proposed a new nomenclature, "bladder
      pain syndrome", and classification system in 2008 for the same condition.
      Treatment strategies can be categorized broadly into four different approaches:
      (i) intravesical drug instillation, (ii) systemic (oral) medical therapy, (iii)
      administration of local treatments, and (iv) surgical procedures for refractory
      disease. Intravesical drug instillation or oral therapies are the mainstay of
      treatment.

PMID- 19837526
TI  - Susceptibility to the main antibiotics of Escherichia coli and Staphylococcus
      aureus strains identified in community acquired infections in France (MedQual,
      2004-2007).
AB  - BACKGROUND: The aim of this study was to determine the susceptibility of
      bacterial strains identified in community-acquired infections. Surveillance was
      made by a network of 32 medical analysis laboratories in the five departments of
      the French Region "Pays de la Loire". METHODS: All Escherichia coli (E. coli) and
      Staphylococcus aureus (S. aureus) strains isolated in these laboratories over a 4
      year period, from January 2004 to December 2007, were included in the
      investigation. RESULTS: Eighty-four thousand and twenty-nine strains were
      collected: 90.6% of E. coli and 9.4% of S. aureus. E. coli isolates were mainly
      isolated from urine (97.2%). S. aureus isolates were more frequently isolated
      from pus (42.30%), from urinary samples (19.53%), or genital tract samples
      (14.36%). This study confirms the worrying E. coli evolution of resistance to
      quinolones. Indeed, during the study period, ofloxacin or norfloxacin
      susceptibility decreased gradually and the susceptibility rate to ciprofloxacin
      decreased slightly during and after 2006 (94.01% in 2005; 92.81% in 2006, and
      91.62% in 2007). One thousand four hundred and thirty-five methicillin-resistant
      S. aureus (MRSA) strains were isolated. We observed a decrease of resistance to
      oxacillin: 20.73% in 2004 and 16.65% in 2006 (p<0.01). In 2007, this resistance
      to oxacillin seemed to increase (18.26%). CONCLUSIONS: Our data confirms the
      serious need to monitor transmission of these strains between community and
      hospitals. A better knowledge of the epidemiological behavior of these BMR will
      contribute to better-adapted antibiotics strategies.

PMID- 19837527
TI  - A structured implicit abstraction method to evaluate whether content of
      counseling before prostate cancer screening is consistent with recommendations by
      experts.
AB  - OBJECTIVE: To assess the content of counseling about prostate-specific antigen
      (PSA) screening. Guidelines recommend informed consent before screening because
      of concerns about benefits versus risks. As part of the professional practice
      standard for informed consent, clinicians should include content customarily
      provided by experts. METHODS: 40 transcripts of conversations between medicine
      residents and standardized patients were abstracted using an instrument derived
      from an expert Delphi panel that ranked 10 "facts that experts believe men ought
      to know." RESULTS: Transcripts contained definite criteria for an average of 1.7
      facts, and either definite or partial criteria for 5.1 facts. Second- and third
      year residents presented more facts than interns (p=0.01). The most common facts
      were "false positive PSA tests can occur" and "use of the PSA test as a screening
      test is controversial." There was an r=0.88 correlation between inclusion by
      residents and the experts' ranking. CONCLUSION: Counseling varied but most
      transcripts included some expert-recommended facts. The absence of other facts
      could be a quality deficit or an effort to prioritize messages and lessen
      cognitive demands on the patient. PRACTICE IMPLICATIONS: Clinicians should adapt
      counseling for each patient, but our abstraction approach may help to assess the
      quality of informed consent over larger populations.

PMID- 19837528
TI  - An evaluation of gender and racial disparity in the decision to treat surgically
      arterial disease.
AB  - OBJECTIVE: In 1994, our hospital reported a significant gender disparity in the
      treatment of peripheral artery disease (PAD). The objective of this study was to
      determine if this gender-based treatment disparity still persists after 15 years.
      METHODS: A retrospective review of patients with PAD and carotid artery disease
      based on vascular laboratory studies was performed from January 2006 to February
      2008. PAD was identified by ankle-brachial index <or= 0.9 or abnormal waveform.
      Treatable carotid artery disease was identified by symptomatic stenosis 60%-99%
      or asymptomatic stenosis 80%-99%. Patients with interventions before January 2006
      were excluded. Demographics, risk factors, and interventions were recorded.
      Univariate and multivariate analyses were performed to identify risk factors and
      independent predictors of intervention. RESULTS: Of 2,313 peripheral artery
      studies, 592 patients with PAD and no prior intervention were identified. Sixty
      five (21.7%) of 299 men and 47 (16.0%) of 293 women underwent angioplasty,
      stenting, endarterectomy, or bypass grafting. This difference was not significant
      (P = .077). However, by multivariate analysis of patients with critical limb
      ischemia, Caucasian race was an independent predictor of intervention (P = .010;
      odds ratio [OR] 3.363). Of 3,505 carotid duplex studies, 253 patients with
      treatable carotid artery disease and no prior intervention were identified.
      Seventy-eight (52.7%) of 148 men and 43 (41.0%) of 105 women underwent carotid
      endarterectomy (CEA) or stenting. This difference was not significant (P = .065).
      However, by multivariate analysis, Caucasian race was identified as an
      independent predictor of intervention (P = .015, OR 3.033). Insurance status was
      not a predictor of intervention in either the PAD (P = .70) or carotid artery
      disease cohort (P = .99). CONCLUSION: Our data reveal that gender was not an
      independent predictor of intervention for PAD or carotid artery disease; however,
      Caucasian race independently predicted a greater likelihood of intervention in
      PAD patients with critical limb ischemia and in the carotid artery disease
      cohort. This study demonstrates the importance of performance assessments in
      uncovering unsuspected treatment disparities.

PMID- 19837529
TI  - Short and midterm results after left subclavian artery coverage during
      endovascular repair of the thoracic aorta.
AB  - BACKGROUND: To analyze the sequelae of the intentional left subclavian artery
      (LSA) coverage during thoracic endovascular aortic repair (TEVAR). METHODS:
      Retrospective analysis of prospectively collected data in a single center.
      Between March 1997 and October 2008, 88 of 220 patients (40%) had thoracic aortic
      lesions that required LSA coverage during TEVAR. Thirty-four of our patients
      (39%) were treated under urgent or emergent conditions for acute pathologies. The
      proximal landing zone was zone 0 in 10 patients (11%), zone 1 in 24 patients
      (27%), and zone 2 in 54 patients (61%). Debranching procedures of the supra
      aortic vessels were performed in patients who were to undergo zone 0 or zone 1
      deployment. Primary LSA revascularization was performed in 22 of the 88 patients
      (25%) at a median of 6 days before TEVAR. Median follow-up was 26.4 months (1-98
      months). RESULTS: Technical success was achieved in 97%. Five primary (9%) and
      two secondary (4%) type Ia endoleaks in patients who underwent zone 2 deployment
      were observed and required further interventions. Fourteen (16%) primary type II
      endoleaks were observed; 10 of them fed by the LSA. Paraplegia rate was lower in
      patients with LSA coverage without revascularization than in other patients (1.5%
      vs 1.9%; odds ratio [OR], 0.774; 95% confidence interval [CI], 0.038-6.173; P =
      1.000). Prior or concomitant infrarenal aortic replacement (P = .0019), renal
      insufficiency (glomerular filtration rate < 90 mL/min/1.73 m(2)) (P = .0024) and
      long segment aortic coverage (>200 mm) (P = .0157) were associated with
      significant higher risk of postoperative paraplegia. Stroke rate was lower in
      patients with LSA coverage without revascularization than in other patients (3%
      vs 3.9%; OR, 0.570; 95% CI, 0.118-2.761; P = .7269). Two patients (3%) developed
      left upper extremity symptoms and another two patients (3%) subclavian steal
      syndrome and required secondary LSA revascularization. The technical success rate
      for LSA revascularization was 94%. CONCLUSION: By using a selective approach to
      the LSA revascularization, coverage of the LSA can be used to extend the proximal
      seal zone for TEVAR without increasing the risk of spinal cord ischemia or
      stroke. Indications for revascularization include long segment aortic coverage,
      prior or concomitant infrarenal aortic replacement, and renal insufficiency. In
      addition, a hypoplastic right vertebral artery, a patent left internal mammary
      artery graft, and a functioning dialysis fistula in the left arm would also be
      indications to perform revascularization.

PMID- 19837530
TI  - Intermediate-term outcomes of endovascular treatment for symptomatic chronic
      mesenteric ischemia.
AB  - OBJECTIVE: Endovascular therapy for chronic mesenteric ischemia (CMI) has been
      increasingly utilized. Early outcomes compare favorably with open mesenteric
      bypass--the current gold standard. The goal of this study is documentation of
      intermediate-term anatomic and functional outcomes of endovascular mesenteric
      revascularization for symptomatic CMI. METHODS: This is a retrospective review of
      all patients undergoing endovascular treatment of symptomatic CMI from July 2002
      to March 2008. Study endpoints included periprocedural mortality, major
      morbidity, patency, symptomatic recurrence, and survival. Endpoints were analyzed
      using actuarial methods. RESULTS: Sixty-six mesenteric arteries (78.8%
      stenotic/21.2% occluded) were treated in 49 patients. One or more vessels were
      treated in each case; however, four mesenteric artery total occlusions (3 SMAs/1
      IMA) could not be crossed. Initial symptom relief was noted in 89.8% (n = 44)
      with no change in 5 patients. Single-vessel treatments were performed in 32
      patients (65.3%) and two-vessel interventions in 17 (34.7%). The 30-day mortality
      rate was 2.0% (n = 1). Major complications occurred in 8 patients (16.3%). The
      mean follow-up duration was 37.4 +/- 2.98 months (range, 0-66). Restenosis on
      follow-up imaging occurred in 64.9% (n = 24) of the 37 patients who had
      radiographic surveillance at a mean follow-up interval of 8.5 +/- 1.9 months and
      was diagnosed most often by Duplex scan or computed tomographic angiography
      (CTA). Fourteen patients (28.6%) developed recurrent symptoms with 13 requiring a
      reintervention. Actuarial 36-month freedom from symptomatic recurrence was 60.9%
      +/- 9.4%. Two-vessel treatment was protective against symptom recurrence (P =
      .0014) and reintervention (P = .0060) by univariate analysis. A total of 19
      reinterventions were required in 14 patients (28.6%) at a mean of 17 months from
      the original treatment. Primary patency at 36 months was 63.9 +/- 8.5%. Actuarial
      survival at 48 months was 81.1% +/- 6.1% with no CMI-related deaths in the study
      cohort. CONCLUSION: Intermediate (3-year) follow-up indicates that significant
      restenosis and symptom recurrence are common following the endovascular treatment
      of symptomatic CMI. Thirty percent of the cohort required a reintervention, one
      third of which were conversions to surgical reconstruction. Similar to the
      surgical paradigm of two-vessel revascularization, endovascular treatment of
      multiple mesenteric arteries produced better outcomes. A first-line endovascular
      approach to patients with CMI is a reasonable clinical strategy, but close follow
      up is mandatory.

PMID- 19837531
TI  - Recurrent popliteal vein aneurysm.
AB  - A 28-year-old female presented with a soft mass in the left popliteal fossa. She
      had a popliteal vein aneurysm repair 4 years ago. Magnetic resonance venography
      and ultrasound revealed a recurrent saccular aneurysm on the site of the repair.
      It measured 3 x 4 cm and had no thrombus. The aneurysm was resected, and as the
      vein had adequate length, it was primarily repaired with an end-to-end
      anastomosis. She was placed on coumadin for 3 months. At follow-up, the vein was
      competent and free of thrombosis.

PMID- 19837533
TI  - Long-term radiographic outcomes of microemboli following carotid interventions.
AB  - OBJECTIVE: Subclinical microemboli on diffusion-weighted magnetic resonance
      imaging (DWI) have been identified immediately following carotid
      revascularization procedures, but the clinical significance and long-term effects
      are largely unknown. The purpose of this study was to evaluate long-term
      radiographic outcomes of these DWI lesions. METHODS: Patients who underwent
      perioperative magnetic resonance imaging (MRI) evaluations for carotid
      interventions at a single institution from July 2004 to December 2008 were
      evaluated, particularly those who had additional follow-up MRI. DWI with apparent
      diffusion coefficient (ADC), fluid-attenuated inversion recovery (FLAIR), and T2
      weighted MRI images were compared to determine long-term effect of microemboli.
      RESULTS: One-hundred sixty-eight consecutive patients (68 carotid artery stenting
      [CAS] and 100 carotid endarterectomy [CEA]) who received perioperative MRI were
      included. All CAS were performed with an embolic protection device. The incidence
      of microemboli was significantly higher in the CAS group than the CEA group
      (46.3% and 12%, respectively, P < .05) despite a relative low incidence of
      procedure-associated neurologic symptoms in both groups (2.9% vs 2%). Thirty
      patients (16 CAS and 14 CEA) who had follow-up MRI were further analyzed and a
      total of 50 postoperative DWI lesions (mean size 46.57 mm(2); range 16 to 128
      mm(2)) were identified among them. During a mean MRI follow-up of 10 months
      (range, 2 to 23 months), residual MRI abnormalities were only identified in DWI
      lesions larger than 60 mm(2) on postoperative MRI and on postoperative FLAIR
      images (n = 5, P < .001). The CEA group had fewer but larger ipsilateral
      distributed emboli (total 12 lesions, mean 79 mm(2)) compared with the CAS group
      (total 38 lesions, mean 27.5 mm(2), P < .05). CONCLUSIONS: The majority of
      microemboli do not have long-term radiographic sequelae. Size and hyperintensity
      on postoperative FLAIR are predictive of residual brain structure abnormality,
      and further neurocognitive evaluations are warranted.

PMID- 19837532
TI  - Adaptive changes in autogenous vein grafts for arterial reconstruction: clinical
      implications.
AB  - For patients with the most severe manifestations of lower extremity arterial
      occlusive disease, bypass surgery using autogenous vein has been the most durable
      reconstruction. However, the incidence of bypass graft stenosis and graft failure
      remains substantial and wholesale improvements in patency are lacking. One
      potential explanation is that stenosis arises not only from over exuberant
      intimal hyperplasia, but also due to insufficient adaptation or remodeling of the
      vein to the arterial environment. Although in vivo human studies are difficult to
      conduct, recent advances in imaging technology have made possible a more
      comprehensive structural examination of vein bypass maturation. This review
      summarizes recent translational efforts to understand the structural and
      functional properties of human vein grafts and places it within the context of
      the rich existing literature of vein graft failure.

PMID- 19837534
TI  - Strength training increases walking tolerance in intermittent claudication
      patients: randomized trial.
AB  - OBJECTIVE: To analyze the effects of strength training (ST) in walking capacity
      in patients with intermittent claudication (IC) compared with walking training
      (WT) effects. METHODS: Thirty patients with IC were randomized into ST and WT.
      Both groups trained twice a week for 12 weeks at the same rate of perceived
      exertion. ST consisted of three sets of 10 repetitions of whole body exercises.
      WT consisted of 15 bouts of 2-minute walking. Before and after the training
      program walking capacity, peak VO(2), VO(2) at the first stage of treadmill test,
      ankle brachial index, ischemic window, and knee extension strength were measured.
      RESULTS: ST improved initial claudication distance (358 +/- 224 vs 504 +/- 276
      meters; P < .01), total walking distance (618 +/- 282 to 775 +/- 334 meters; P <
      .01), VO(2) at the first stage of treadmill test (9.7 +/- 2.6 vs 8.1 +/- 1.7
      mL.kg(-1).minute; P < .01), ischemic window (0.81 +/- 1.16 vs 0.43 +/- 0.47 mm Hg
      minute meters(-1); P = .04), and knee extension strength (19 +/- 9 vs 21 +/- 8 kg
      and 21 +/- 9 vs 23 +/- 9; P < .01). Strength increases correlated with the
      increase in initial claudication distance (r = 0.64; P = .01) and with the
      decrease in VO(2) measured at the first stage of the treadmill test (r = -0.52; P
      = .04 and r = -0.55; P = .03). Adaptations following ST were similar to the ones
      observed after WT; however, patients reported lower pain during ST than WT (P <
      .01). CONCLUSION: ST improves functional limitation similarly to WT but it
      produces lower pain, suggesting that this type of exercise could be useful and
      should be considered in patients with IC.

PMID- 19837535
TI  - Prevalence, risk factors, and clinical correlates of ulnar artery occlusion in
      the general population.
AB  - BACKGROUND: Occlusion of the ulnar artery is found in a substantial proportion of
      elderly patients. The aim of this study was to estimate the prevalence of ulnar
      artery occlusion in a sample of the general population of France, look for its
      risk factors, and evaluate its clinical correlates. METHODS: This study was an
      offshoot of a cross-sectional epidemiologic study in the general population of
      four locations in France (Tarentaise, Grenoble, Nyons, and Toulon). In phase I,
      random samples of 2000 individuals per location aged >or=18 years old were
      interviewed by phone for screening of Raynaud phenomenon. In phase II, subsamples
      of individuals were invited to a medical interview and physical examination where
      the presence of Raynaud phenomenon and occupational risk factors were recorded
      and a bilateral clinical Allen test was performed for the detection of ulnar
      artery occlusion. Phase II comprised 688 women and 335 men. RESULTS: In 36 men
      and seven women, at least one occluded ulnar artery was found. The estimated
      prevalence was 9.6% in men and 1.0% in women (P < .001). The occluded artery was
      more often in the dominant hand of both men (8.1% vs 2.4%; P < .001) and women
      (0.9% vs 0.4%; P = .34). Ulnar artery occlusion was found more often in men aged
      >50 years (16.4%) than in younger men (1.4%; P < .001). Besides age, male sex,
      and dominant side, the only independent risk factor was an occupational exposure
      in men to repeated palmar trauma, with a significant quantitative relationship in
      the frequency of the impacts (P < .001) and the duration of the exposure (P <
      .001). Exposures to hand-held vibrating tools and cigarette smoking did not show
      a significant relationship in the multivariate analysis. Most individuals with
      ulnar artery occlusion did not have associated complaints; however, the
      diagnostic criteria for Raynaud phenomenon was validated in 13 of the 36 affected
      men. The association remained significant after adjusting for occupational
      exposure to vibrating tools. One individual reported a previous episode
      consistent with an attack of permanent digital ischemia. CONCLUSION: This study
      confirms a substantial prevalence of ulnar artery occlusions in the general
      population, mostly in middle-aged and elderly men, which appears to be
      principally related to an occupational exposure to repeated occupational palmar
      trauma. Although there is a significant association with Raynaud phenomenon, most
      often the consequences of this occlusion remain subclinical.

PMID- 19837536
TI  - Joint torques and powers are reduced during ambulation for both limbs in patients
      with unilateral claudication.
AB  - OBJECTIVES: Symptomatic peripheral arterial disease (PAD) results in significant
      gait impairment. In an attempt to fully delineate and quantify these gait
      alterations, we analyzed joint kinematics, torques (rotational forces), and
      powers (rotational forces times angular velocity) in patients with PAD with
      unilateral claudication for both the affected and nonaffected legs. METHODS:
      Twelve patients with unilateral PAD (age, 61.69 +/- 10.53 years, ankle-brachial
      index [ABI]: affected limb 0.59 +/- 0.25; nonaffected limb 0.93 +/- 0.12) and 10
      healthy controls (age, 67.23 +/- 12.67 years, ABI >1.0 all subjects) walked over
      a force platform to acquire gait kinetics, while joint kinematics were recorded
      simultaneously. Data were collected for the affected and nonaffected limbs during
      pain free (PAD-PF) and pain induced (PAD-P) trials. Kinetics and kinematics were
      combined to quantify torque and powers during the stance period from the hip,
      knee, and ankle joints. RESULTS: The affected limb demonstrated significantly (P
      <.05) reduced ankle plantar flexion torque compared to controls during late
      stance in both PAD-PF and PAD-P trials. There were significant reductions in
      ankle plantar flexion power generation during late stance for both the affected
      (P <.05) and nonaffected limbs (P <.05) compared to control during PAD-PF and PAD
      P trials. No significant differences were noted in torque comparing the
      nonaffected limbs in PAD-PF and PAD-P conditions to control for knee and hip
      joints throughout the stance phase. Significant reductions were found in knee
      power absorption in early stance and knee power generation during mid stance for
      both limbs of the patients with PAD as compared to control (P <.05). CONCLUSION:
      Patients with PAD with unilateral claudication demonstrate significant gait
      impairments in both limbs that are present even before they experience any
      claudication symptoms. Overall, our data demonstrate significantly reduced ankle
      plantar flexion torque and power during late stance with reduced knee power
      during early and mid stance for the affected limb. Further studies are needed to
      determine if these findings are dependent on the location and the severity of
      lower extremity ischemia and whether the changes in the nonaffected limb are the
      result of underlying PAD or compensatory changes from the affected limb
      dysfunction.

PMID- 19837537
TI  - Cost-effectiveness of abdominal aortic aneurysm repair based on aneurysm size.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of endovascular repair (EVAR) for
      small abdominal aortic aneurysms (AAA). METHODS: We developed a Markov model of a
      hypothetical 68-year-old cohort to determine the cost-effectiveness of early EVAR
      for "small" AAAs (4.0 cm-5.4 cm) compared with elective repair (open or
      endovascular) at the traditional cut-off of 5.5 cm. Repair options for 5.5-cm
      AAAs include both endovascular and open procedures. Probabilities were obtained
      from the literature. Costs reflected direct costs in 2007 dollars. Outcomes were
      reported as quality-adjusted life-years (QALYs). RESULTS: The model demonstrated
      that early EVAR for 4.0 cm-5.4 cm AAAs led to fewer QALYs at greater costs when
      compared with observational management with elective repair at 5.5 cm.
      Sensitivity analyses suggested that early EVAR of 4.6 cm-4.9 cm AAAs can be cost
      effective if the long-term mortality rate after EVAR is <or=1.91% per year or if
      the quality of life after EVAR is improved. Likewise, if the quality of life
      before repair is low, EVAR for AAAs >or=4.6 cm may be cost-effective. With a >70%
      probability, observational management until AAA diameter is 5.5 cm will be the
      cost-effective option. CONCLUSIONS: This analysis demonstrated that early EVAR
      for AAAs <5.5 cm is not likely to be cost-effective compared with elective repair
      at 5.5 cm. However, EVAR for small AAAs may become cost-effective when
      differences in quality of life and mortality are considered.

PMID- 19837538
TI  - Lower extremity angioplasty: impact of practitioner specialty and volume on
      practice patterns and healthcare resource utilization.
AB  - OBJECTIVES: Lower extremity percutaneous transluminal angioplasty (LE PTA) is
      currently performed by a variety of endovascular specialists. We hypothesized
      that cardiologists (CRD) and vascular surgeons (VAS) may have different practice
      patterns, indications for intervention, and hospital resource utilization.
      METHODS: Using the State Inpatient Databases for New Jersey (2003-2007), patients
      with elective admission undergoing PTA procedures with indications of
      claudication, rest pain, and gangrene/ulceration were examined. Physician
      specialty was determined based on all procedures performed. We contrasted by
      specialty, the indication for LE PTA for the procedure, volume, and hospital
      resource utilization. RESULTS: Of the 1887 cases of LE PTA, VAS performed 866
      (45.9%) and CRD 1021 (54.1%) procedures. The mean patient age was 68.0 years
      (CRD) vs 70.7 years (VAS), P = .0163. Indications for intervention were compared
      for CRD vs VAS: claudication 80.7% vs 60.7%, (P < .002); rest pain 6.2% vs 16.0%,
      (P < .002); gangrene/ulceration 13.1% vs 23.3%, (P < .002). Stents (64.8% of
      cases) were utilized similarly among physicians (P = .18), and mean hospital
      length of stay were similar (2.38 days vs 2.41 days, P = .85). Hospital charges
      by indication varied between CRD vs VAS (all procedures: $49,748 vs $42,158 [P <
      .0001]). Revenue center charges were different between CRD vs VAS: medical
      surgical supply $19,128 vs $12,737, (P < .0001); pharmacy $1,959 vs $1,115, (P <
      .0001). Only 10.7% of CRD were high volume practitioners, compared with 36.8%
      among VAS (P < .05). High volume practitioners had significantly lower hospital
      charges ($41,730 vs $51,014, P < .001). CONCLUSIONS: Cardiologists performing
      lower extremity angioplasty were more likely to treat patients with claudication
      than those with rest pain or gangrene/ulceration. Despite treating younger
      patients with less severe peripheral vascular disease, cardiologists used
      significantly greater hospital resources. High practitioner volume, regardless of
      specialty, was associated with lower hospital resource utilization. Reducing
      variations in indication and practitioner volume may offer substantial cost
      savings for lower extremity endovascular interventions.

PMID- 19837539
TI  - Use of autologous bone marrow mononuclear cell implantation therapy as a limb
      salvage procedure in patients with severe peripheral arterial disease.
AB  - BACKGROUND: Few options other than amputation exist for some patients with
      peripheral arterial occlusive disease (PAD) and severe anatomical limitations.
      METHODS: This prospective study presents short-term results of dual intramuscular
      and intra-arterial autologous bone marrow mononuclear cell (BM-MNC) implantation
      for the treatment of patients with severe PAD in whom amputation was considered
      the only viable treatment option. Baseline, two-week, and three-month evaluations
      were conducted. Ankle brachial indices (ABI) were calculated for both the dorsal
      pedis and the posterior tibial arteries. Rest pain and ulcer healing also were
      assessed. Success was defined as meeting the following four criteria: improvement
      in ABI measurements; relief of rest pain; ulcer healing, if applicable; and
      absence of major limb amputations. Patients not undergoing major limb amputations
      continued to be monitored for subsequent procedures. RESULTS: Nine patients for
      whom limb amputation was recommended underwent this procedure. The study
      population was comprised of five females and four males, with a mean age of 61.7
      years. Eight (88.9%) patients had rest pain. Seven (77.8%) patients also had
      diabetes. Non-healing ulcers were present in eight (88.9%) cases. After the
      procedure, non-significant improvements of 0.12 and 0.08 in ABI were observed for
      the dorsalis pedis and posterior tibial ankle arteries, respectively. Three
      (33.3%) major amputations subsequently were performed, including a below-knee
      amputation 4.1 weeks after the BM-MNC implantation and two above-knee amputations
      at 5.4 and 11.0 weeks after the procedure. The six (66.7%) patients who did not
      have major amputations demonstrated improvement in symptom severity three months
      after the procedure, as evidenced by alleviation of rest pain and improvements by
      at least one level in Rutherford and Fontaine classifications, and have not
      required amputations at a mean follow-up of 7.8 months. Complete wound healing
      was achieved within three months in all patients who had ulcers prior to BM-MNC
      implantation and for whom amputation was not required. This specific BM-MNC
      implantation technique was fully successful in three (33.3%) patients, as major
      amputation was avoided and the other applicable criteria were met. Five (55.6%)
      additional patients demonstrated success in at least one of the four criteria.
      CONCLUSIONS: With eight (88.9%) of nine patients showing some level of
      improvement and amputation avoided in six (66.7%) patients, these short-term
      results indicate the use of BM-MNC implantation as a means of limb salvage
      therapy for patients with severe PAD shows promise in postponing or avoiding
      amputation in a patient population currently presented with few alternatives to
      amputation.

PMID- 19837540
TI  - Prevention of cardiopulmonary embolization of polymethylmethacrylate cement
      fragment after kyphoplasty with insertion of inferior vena cava filter.
AB  - We report the case of a 51-year-old woman who underwent kyphoplasty with
      polymethylmethacrylate for painful compression fracture of the third lumbar
      vertebra. Infiltration of cement into the inferior vena cava, noted
      intraoperatively, was confirmed with postoperative CT scan. A Greenfield filter
      was placed to prevent cardiopulmonary embolization of the fragment. On follow-up
      x-rays, the cement fragment was found to have detached and embolized into the
      vena cava filter. Endovascular technique was used to retrieve it to the common
      femoral vein with subsequent successful removal of the crescent-like fragment
      with operative exploration. Patient was asymptomatic at four-week follow-up
      visit.

PMID- 19837541
TI  - Recurrence of a popliteal venous aneurysm.
AB  - We report the case of a 40-year-old man with a recurrent popliteal vein aneurysm
      diagnosed 2 years after initial lateral aneurysmectomy. Definitive management
      consisted of popliteal vein aneurysm resection and reconstruction with an
      interposition spiral vein graft. Our case suggests that aneurysm vein resection
      and interposition vein graft should be the preferred surgical option. Also,
      patients treated may benefit from longer follow-up in light of the potential
      morbidity from recurrence if undetected.

PMID- 19837542
TI  - High prevalence of right-to-left shunt in patients with symptomatic great
      saphenous incompetence and varicose veins.
AB  - BACKGROUND: Varicose veins are common and increasingly are being treated by less
      invasive endoscopic methods such as foam sclerotherapy. Patent foramen ovale
      (PFO) is also common, present in approximately one-quarter of adults. PFO allows
      bubbles introduced by foam sclerotherapy to cross into the general circulation,
      potentially causing cerebral artery gas embolization with unevaluated
      consequences. METHODS: Men and women aged 18 to 60 years with symptomatic
      varicose veins (CEAP C(3-5)) responded to an advertisement to recruit volunteers
      for a study on endovenous microfoam ablation (EMA). Participants' veins were
      screened by duplex ultrasound imaging, and those with isolated great saphenous
      vein (GSV) incompetence were tested for right-to-left (R-L) vascular shunt using
      transcranial Doppler (TCD) of the middle cerebral artery to detect the presence
      of bubble emboli after an injection of an agitated saline, blood, and air mixture
      as a contrast at rest and with the Valsalva maneuver. RESULTS: Of 221
      participants tested for R-L shunt, 85 (38.5%) were positive at rest (95%
      confidence interval [CI], 32.5-45.2) and 114 (51.8%) were positive after the
      Valsalva maneuver (95% CI, 45.4-58.5). A total 130 patients (58.8%) were positive
      for R-L shunt at rest or after Valsalva (95% CI, 52.5%-65.1%). This is
      significantly higher than the reported 26% prevalence of PFO in the general
      population (95% CI, 24.4-30.1). CONCLUSIONS: The prevalence of R-L shunt in
      patients with GSV incompetence CEAP C(3-5) in this study was higher than expected
      in the general population. TCD does not differentiate between intracardiac shunts
      and intrapulmonary shunts, so this observation needs further investigation. This
      link between R-L shunt and varicose veins is novel and, whether etiologic or
      functional, may improve the understanding of both conditions. The findings have
      importance in the treatment of varicose veins with foam sclerotherapy and EMA.

PMID- 19837544
TI  - Recovery from hind limb ischemia is less effective in type 2 than in type 1
      diabetic mice: roles of endothelial nitric oxide synthase and endothelial
      progenitor cells.
AB  - OBJECTIVE: We sought to directly compare the effects of type 1 and type 2
      diabetes on postischemic neovascularization and evaluate the mechanisms
      underlying differences between these groups. We tested the hypothesis that type 2
      diabetic mice have a greater reduction in endothelial nitric oxide synthase
      (eNOS) expression, a greater increase in oxidative stress, and reduced
      arteriogenesis and angiogenesis, resulting in less complete blood flow recovery
      than type 1 diabetic mice after induction of hind limb ischemia. METHODS: Hind
      limb ischemia was generated by femoral artery excision in streptozotocin-treated
      mice (model of type 1 diabetes), in Lepr(db/db) mice (model of type 2 diabetes),
      and in control (C57BL/6) mice. Dependent variables included eNOS expression and
      markers of arteriogenesis, angiogenesis, and oxidative stress. RESULTS:
      Postischemia recovery of hind limb perfusion was significantly less in type 2
      than in type 1 diabetic mice; however, neither group demonstrated a significant
      increase in collateral artery diameter or collateral artery angioscore in the
      ischemic hind limb. The capillary/myofiber ratio in the gastrocnemius muscle
      decreased in response to ischemia in control or type 1 diabetic mice but remained
      the same in type 2 diabetic mice. Gastrocnemius muscle eNOS expression was lower
      in type 1 and 2 diabetic mice than in control mice. This expression decreased
      after induction of ischemia in type 2 but not in type 1 diabetic mice. The
      percentage of endothelial progenitor cells (EPC) in the peripheral blood failed
      to increase in either diabetic group after induction of ischemia, whereas this
      variable significantly increased in the control group in response to ischemia.
      EPC eNOS expression decreased after induction of ischemia in type 1 but not in
      type 2 diabetic mice. EPC nitrotyrosine accumulation increased after induction of
      ischemia in type 2 but not in type 1 diabetic mice. EPC migration in response to
      vascular endothelial growth factor was reduced in type 1 and type 2 diabetic mice
      vs control mice. EPC incorporation into tubular structures was less effective in
      type 2 diabetic mice. Extensive fatty infiltration was present in ischemic muscle
      of type 2 but not in type 1 diabetic mice. CONCLUSION: Type 2 diabetic mice
      displayed a significantly less effective response to hind limb ischemia than type
      1 diabetic mice.

PMID- 19837545
TI  - Aggressive lipid-lowering is more effective than moderate lipid-lowering
      treatment in carotid plaque stabilization.
AB  - OBJECTIVE: Atherosclerotic plaque stabilization is a promising strategy to
      prevent cerebrovascular events in patients with carotid atherosclerosis. Vascular
      calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have
      emerged as novel cardiovascular biomarkers. This open-label, prospective study
      aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is
      more effective than moderate lipid-lowering in increasing carotid plaque
      echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum OPN
      and OPG levels in patients with moderate carotid stenosis. METHODS: One hundred
      forty patients (64 males, 76 females), aged 50 to 75 years, with carotid stenosis
      (North American Symptomatic Carotid Endarterectomy Trial [NASCET]: 30%-60% for
      symptomatic and 30%-70% for asymptomatic), but without indications for surgical
      intervention, were enrolled. Patients with coronary heart disease, renal failure,
      hypothyroidism, osteoporosis, and ongoing use of statins were excluded. Patients
      were randomly assigned to: Group A (N = 70): Moderate lipid-lowering therapy with
      low-dose of atorvastatin (10 mg-20 mg) to target LDL-C <100 mg/dL. Group B (N =
      70): Aggressive lipid-lowering therapy with high-dose of atorvastatin (80 mg) to
      target LDL-C <70 mg/dL. Blood pressure, lipid and glycemic indexes, hsCRP, serum
      OPN, and OPG were measured at baseline and after 12 months as well as the GSM
      score. Independent samples t test, paired samples t test, Pearson correlation,
      and multiple regression analysis were used (P < .05). RESULTS: There were no
      significant differences between groups at baseline. Three patients in group A
      experienced either cerebrovascular or cardiac ischemic attacks, while two
      patients in group B underwent coronary angioplasty during follow-up. Group B
      showed a more pronounced improvement in total cholesterol and LDL-cholesterol
      compared with group A (P < .05). Moreover, atorvastatin treatment suppressed
      serum hsCRP, OPN, and OPG levels from baseline in both groups (P < .001).
      Notably, aggressive treatment decreased OPN (P = .012) and OPG (P = .025) levels
      to a greater degree compared with moderate treatment. Similarly, GSM score was
      remarkably increased in both groups, but that augmentation was greater in group B
      (from 66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to
      85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was
      noted in both treatment arms. Importantly, the aforementioned reduction in OPN (r
      = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely
      associated with GSM score changes in univariate and standard multiple regression
      analysis (R(2) = 0.411, P = .021). CONCLUSIONS: Among patients with moderate
      carotid stenosis, an aggressive atorvastatin regimen enhanced carotid plaque
      echogenicity and reduced serum OPN and OPG levels to a greater extent than
      respective moderate atorvastatin therapy. Most importantly, those atorvastatin
      induced effects were associated with OPN and OPG suppression in a dose-dependent
      manner.

PMID- 19837547
TI  - Prediction rule for cardiovascular events and mortality in peripheral arterial
      disease patients: data from the prospective Second Manifestations of ARTerial
      disease (SMART) cohort study.
AB  - BACKGROUND: Patients with peripheral arterial disease (PAD) are at high risk of
      secondary cardiovascular death and events such as myocardial infarction or
      stroke. To minimize this elevated risk, cardiovascular risk factors should be
      treated in all PAD patients. Secondary risk management may benefit from a
      prediction tool to identify PAD patients at the highest risk who could be
      referred for an additional extensive workup. Stratifying PAD patients according
      to their risk of secondary events could aid in achieving optimal therapy
      compliance. To this end we developed a prediction model for secondary
      cardiovascular events in PAD patients. METHODS: The model was developed using
      data from 800 PAD patients who participated in the Second Manifestations of
      ARTerial disease (SMART) cohort study. From the baseline characteristics, 13
      candidate predictors were selected for the model development. Missing values were
      imputed by means of single regression imputation. Continuous predictors were
      truncated and transformed where necessary, followed by model reduction by means
      of backward stepwise selection. To correct for over-fitting, a bootstrapping
      technique was applied. Finally, a score chart was created that divides patients
      in four risk categories that have been linked to the risk of a cardiovascular
      event during 1- and 5-year follow-up. RESULTS: During a mean follow-up of 4.7
      years, 120 events occurred (27% nonfatal myocardial infarction, 21% nonfatal
      stroke, and 52% mortality from vascular causes), corresponding to a 1- and 5-year
      cumulative incidence of 3.1% and 13.2%, respectively. Important predictors for
      the secondary risk of a cardiovascular event are age, history of symptomatic
      cardiovascular disease, systolic blood pressure, high-density lipoprotein
      cholesterol, smoking behavior, ankle-brachial pressure index, and creatinine
      level. The risk of a cardiovascular event in a patient as predicted by the model
      was 0% to 10% and 1% to 28% for the four risk categories at 1- and 5-year follow
      up, respectively. The discriminating capacity of the prediction model, indicated
      by the c statistic, was 0.76 (95% confidence interval, 0.71-0.80). CONCLUSION: A
      prediction model can be used to predict secondary cardiovascular risk in PAD
      patients. We propose such a prediction model to allow for the identification of
      PAD patients at the highest risk of a cardiovascular event or cardiovascular
      death, which may be a viable tool in vascular secondary health care practice.

PMID- 19837548
TI  - [The implication of a direct antithrombine in the appearance of (serious)
      postoperative acute respiratory distress].
AB  - We present the case of a 73-year-old man, operated on for paralyzing sciatica,
      who displayed acute postoperative respiratory distress and intra-alveolar
      haemorrhage following the administration of dabigatran etexilate, a new oral
      antithrombin used in the prevention of venous thromboembolism. This serious
      incident occurred in a patient who had a 20-year history of chronic
      thrombocytopenia (platelet level at 100G/l) and a heparin-induced
      thrombocytopenia and in whom no other aetiology was found (tuberculosis, pneumo
      renal syndrome, etc.). The postoperative prevention of thromboembolic events in a
      patient with high risk bleeding requires intensive monitoring, notably, when
      prescribing new drugs such as new anticoagulant agents.

PMID- 19837549
TI  - Low incidence of postoperative complications due to pin placement in computer
      navigated total knee arthroplasty.
AB  - Computer-navigated joint arthroplasty surgery using optical tracking systems
      requires arrays fixated to bone via pins. Reports of fractures at pin sites have
      raised concern about safety. We reviewed the postoperative complications
      occurring in a single-surgeon series of 984 consecutive primary total knee
      arthroplasties. All pins were placed unicortically and connected by a dual pin
      array. Femoral pins were placed into the medial epicondyle, and tibial pins were
      placed in the shaft 10 cm inferior to the joint line. There were no fractures.
      Seventeen (1.7%) patients had minor pin-related complications. Twelve patients
      had a superficial infection around the tibial pin sites, which resolved with
      antibiotics. None of the infections required readmission or reoperation. We
      believe pin placement to be safe and effective with proper technique.

PMID- 19837550
TI  - Neuraxial hematoma and paralysis after enoxaparin administration 3 days after
      attempted spinal anesthesia for total knee arthroplasty.
AB  - A 69-year-old man underwent a total knee arthroplasty. Spinal anesthesia was
      attempted, but when unsuccessful, a general anesthesia was given. The surgery and
      rehabilitation were uneventful until postoperative day 3 when a pulmonary
      embolism was diagnosed. He was placed on enoxaparin at a therapeutic dose that
      begun more than 72 hours after his attempted spinal. He developed a spinal
      hematoma and was paralyzed. The literature has no recommendations for using
      enoxaparin at therapeutic doses after regional anesthesia. There is no previous
      report to suggest that a patient 72 hours after surgery is still at risk from a
      neuraxial hematoma.

PMID- 19837551
TI  - Structural augmentation with biomaterial-loaded allograft threaded cage for the
      treatment of femoral head osteonecrosis.
AB  - Seventy-six patients with femoral head necrosis were allocated to a program of
      either core decompression (control group) or core decompression and implantation
      of a biomaterial-loaded allograft threaded cage (treatment group). All patients
      were followed up prospectively clinically and radiographically. In the control
      group, no significant improvement in Harris hip score was found, and 13 of the 22
      hips had deteriorated to stage III. In the treatment group, the mean Harris hip
      score was improved from 62.8 to 81.6; the clinical success rate at 36 months
      postoperatively was 91%. Collapse was seen in 1 hip, and another 3 hips exhibited
      progressive collapse. The procedure is attractive as a minimally invasive and
      salvage procedure, which shows encouraging success rates and early clinical
      results in patients with Steinberg stage I-II osteonecrosis.

PMID- 19837552
TI  - Subtrochanteric femur fracture after core decompression and placement of a
      tantalum strut for osteonecrosis of the femoral head.
AB  - Multiple treatment options have been described to treat osteonecrosis of the
      femoral head, all with the goal of slowing or reversing the disease process and
      preventing the need for arthroplasty in a young patient population. Core
      decompression of the femoral head to allow revascularization is a commonly used
      technique that can now be supplemented by placement of the Osteonecrosis
      Intervention Implant (Zimmer, Warsaw, Ind). It consists of a tantalum strut that
      acts as a buttress for the subchondral bone of the femoral head. In this case,
      our patient underwent this procedure with subsequent subtrochanteric fracture.
      The factors leading to this iatrogenic injury are location of implant insertion,
      patient selection, and premature ambulation.

PMID- 19837553
TI  - Retracted: Double chevron subtrochanteric shortening derotational osteotomy in
      cementless total hip arthroplasty for Crowe type IV congenital dislocation of the
      hip.

PMID- 19837554
TI  - Increased tender point counts before and after total hip arthroplasty are
      associated with poorer outcomes but are not individually predictive.
AB  - In a prospective study, total hip arthroplasty (THA) patients were assessed
      preoperatively and postoperatively (n = 95) to determine if tender points (TPs)
      are associated with poor THA outcomes. Patients with high follow-up TP counts had
      higher visual analog scale (VAS) for pain and sleep, higher follow-up Western
      Ontario and McMaster Universities Arthritis Index (pain, stiffness, function),
      lower Health Assessment Questionnaire, Harris Hip, and Short Form 36 (physical
      functioning, bodily pain, physical component summary) scores. High follow-up TP
      were associated with increased pain, pain not relieved by surgery, poor function,
      and poor sleep. Visual analog scale pain and sleep, Short Form 36 (physical
      functioning, bodily pain), Western Ontario and McMaster Universities Arthritis
      Index, Health Assessment Questionnaire, and Harris hip scores improved
      significantly after THA; TP scores did not. Higher preoperative TP were
      predictive of higher follow-up TP but were poorly predictive of poor outcome
      measures after surgery in individual patients, suggesting that preoperative TPs
      are not [corrected] contraindicative for THA.

PMID- 19837555
TI  - Sciatic nerve injury in total hip resurfacing: a biomechanical analysis.
AB  - The condition of the gluteal sling was a significant factor in determining the
      pressure experienced by the sciatic nerve during acetabular exposure in total hip
      resurfacing via a posterior approach. The position of the knee did not play a
      significant role at this stage of the procedure. Average pressures were not
      elevated above a predefined injury level during positioning for femoral
      preparation. During hip reduction, knee positioning seemed to play a significant
      role in pressures placed on the sciatic nerve. These findings suggest that
      releasing the gluteal sling during a posterior approach for total hip resurfacing
      may help to prevent postoperative sciatic nerve palsies. Consideration should
      also be given to at least partially flexing the knee during hip reduction in this
      procedure.

PMID- 19837556
TI  - Temporary drainage clamping after total knee arthroplasty: a meta-analysis of
      randomized controlled trials.
AB  - Drainage-clamping methods are thought to be effective in reducing blood loss
      after total knee arthroplasty (TKA). We conducted a systematic review to examine
      if these methods were effective without increasing the risk of complications.
      After a comprehensive search, 6 randomized controlled trials involving 603 knees
      and comparing clamping drainage and the immediate release of the drain after
      elective TKA were included in this analysis. The results demonstrated that
      drainage clamping could decrease the volume of drainage, but only clamping for no
      less than 4 hours could reduce the true blood loss. There was no significant
      difference between the 2 groups regarding blood transfusion, postoperative range
      of motion, incidence of thromboembolic events, and wound complications. The
      current evidence cannot confirm the advantage of clamping drainage after TKA.

PMID- 19837557
TI  - Navigated percutaneous screw fixation of a periprosthetic acetabular fracture.
AB  - Periprosthetic fractures are severe complications of total hip arthroplasty with
      increasing incidence. Most fractures are localized around the femoral component
      of prosthesis, whereas periacetabular fractures are rare and their management is
      difficult. In most cases, an operative procedure with revision and exchange of
      the acetabular cup is necessary. The approaches are demanding and an increased
      risk of complications is reported. We present the case of a female patient with a
      cementless total hip arthroplasty due to severe arthritis, suffering of an
      infratectal transverse periprosthetic fracture. After an initial conservative
      treatment attempt, we performed a minimally invasive screw fixation using
      navigated 2-dimensional fluoroscopic guidance. In this report, the literature for
      treatment recommendations is reviewed and the chosen navigation technique
      discussed.

PMID- 19837558
TI  - Failure of the modular neck in a total hip arthroplasty.
AB  - Modular femoral necks in total hip arthroplasty are promoted as giving the
      surgeon more options during surgery and as being safe. We report a case of
      fatigue fracture in the modular neck of a femoral implant 3 1/2 years after
      implantation. The probable design errors leading to product failure are
      discussed.

PMID- 19837559
TI  - Are acetabular component alignment guides for total hip arthroplasty accurate?
AB  - The acetabular component orientation of total hip arthroplasty is of critical
      importance to the clinical results. Although navigation systems have recently
      been introduced, acetabular component alignment guides are still used in most of
      ordinary hospitals. However, the accuracy of alignment guides themselves has not
      been evaluated. Fifteen types of alignment guide were examined. In all the
      alignment guides, the angles actually indicated and those stated by manufacturers
      were different. Our results showed that usage of modern alignment guides
      inherently misleads anteversion into decrease by a mean of 6 degrees (maximum, 12
      degrees ) and inclination into increase by a mean of 2 degrees (maximum: 4
      degrees ). Such setting of alignment guides could be one of the factors of error
      in acetabular component orientation.

PMID- 19837560
TI  - Venous thromboembolism: management by American Association of Hip and Knee
      Surgeons.
AB  - A 2008 survey of American Association of Hip and Knee Surgeons membership
      explored current venous thromboembolism (VTE) protocols for lower-extremity total
      joint surgery. Fifty-three percent reported a change in VTE-related practices in
      the last 5 years. More than 70% reported that their primary hospital now mandates
      VTE prophylaxis. Although 74% of their primary hospitals recognized the American
      College of Chest Physicians guidelines, 68% of surgeons felt the American Academy
      of Orthopaedic Surgeons guidelines were more relevant to their practice.
      Respondents believe low molecular weight heparin to be the most efficacious but
      aspirin to be the easiest to use and has the lowest risks of bleeding and wound
      drainage. Warfarin was the most used in hospital prophylaxis, and 90% of
      respondents targeted an international normalized ratio of 1.6 to 2.5. Practice
      patterns continue to evolve, and there remains no consensus on specific treatment
      protocols or preferences.

PMID- 19837561
TI  - The singer's voice range profile: female professional opera soloists.
AB  - This work concerns the collection of 30 voice range profiles (VRPs) of female
      operatic voice. We address the questions: Is there a need for a singer's protocol
      in VRP acquisition? Are physiological measurements sufficient or should the
      measurement of performance capabilities also be included? Can we address the
      female singing voice in general or is there a case for categorizing voices when
      studying phonetographic data? Subjects performed a series of structured tasks
      involving both standard speech voice protocols and additional singing tasks.
      Singers also completed an extensive questionnaire. Physiological VRPs differ from
      performance VRPs. Two new VRP metrics, the voice area above a defined level
      threshold and the dynamic range independent from the fundamental frequency
      (F(0)), were found to be useful in the analysis of singer VRPs. Task design had
      no effect on performance VRP outcomes. Voice category differences were mainly
      attributable to phonation frequency-based information. Results support the
      clinical importance of addressing the vocal instrument as it is used in
      performance. Equally important is the elaboration of a protocol suitable for the
      singing voice. The given context and instructions can be more important than task
      design for performance VRPs. Yet, for physiological VRP recordings, task design
      remains critical. Both types of VRPs are suggested for a singer's voice
      evaluation.

PMID- 19837562
TI  - Can we talk? Discussing "cases" amongst ourselves.

PMID- 19837563
TI  - Different measures of treatment effect for different research questions.

PMID- 19837564
TI  - Clustering and commonalities among autoimmune diseases.
AB  - The concept that autoimmune diseases are characterized by shared (common) threads
      is well illustrated by their propensity to co-associate in a patient or direct
      relatives, as coexistences or overlaps. Recognized are two major autoimmune
      clusters, "thyrogastric" (mostly organ-specific) and "lupus-associated" (mostly
      multisystem). Additionally, some autoimmune diseases distribute within either
      cluster and a few appear not to associate. Also, within each cluster there are
      overlaps constituting virtually a distinct syndrome. These patterns of
      coexistence/overlaps depend predominantly on genetic determinants as judged by
      data accruing from numerous highly powered genome-wide association studies. Gene
      polymorphisms thus revealed include those that may determine tissue targeting
      particularly HLA alleles (and others), the (numerous) genes that influence
      orderly progression (or tolerogenesis) among immune responses from innate
      immunity to effector processes, genes that influence pathways of apoptosis, and
      genes that influence vulnerability of target organs to immune-mediated damage. A
      telling illustration is provided by immune-mediated colonic diseases wherein
      there is now a demonstrated capability to allocate the multiple risk genes to
      either Crohn's disease, ulcerative colitis, or both as inflammatory bowel
      disease. Precisely accurate clinical data-bases and serological reactivities,
      combined with deepening molecular genetic analyses, have much promise for a
      better understanding of autoimmunity.

PMID- 19837566
TI  - Grey and white matter abnormalities are associated with impaired spatial working
      memory ability in first-episode schizophrenia.
AB  - Spatial working memory (SWM) dysfunction has been suggested as a trait marker of
      schizophrenia and implicates a diffuse network involving prefrontal, temporal and
      parietal cortices. However, structural abnormalities in both grey and white
      matter in relation to SWM deficits are largely unexplored. The current magnetic
      resonance imaging (MRI) study examined this relationship in a sample of young
      first-episode schizophrenia (FES) patients using a whole-brain voxel-based
      method. SWM ability of 21 FES patients and 41 comparable controls was assessed by
      the CANTAB SWM task. Using an automated morphometric analysis of brain MRI scans,
      we assessed the relationship between SWM abilities and both grey matter volume
      and white matter density in both groups. Our findings demonstrated the different
      directionality of the association between SWM errors and grey matter volume in
      left frontal regions and white matter tracts connecting these regions with
      temporal and occipital areas between FES patients and controls. This suggests
      that the substrate underpinning the normal variability in SWM function in healthy
      individuals may be abnormal in FES, and that the normal neurodevelopmental
      processes that drive the development of SWM networks are disrupted in
      schizophrenia.

PMID- 19837565
TI  - Genome wide high density SNP-based linkage analysis of childhood absence epilepsy
      identifies a susceptibility locus on chromosome 3p23-p14.
AB  - Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE)
      characterised by typical absence seizures manifested by transitory loss of
      awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to
      the aetiology is well recognised but the mechanism of inheritance and the genes
      involved are yet to be fully established. A genome wide single nucleotide
      polymorphism (SNP)-based high density linkage scan was carried out using 41
      nuclear pedigrees with at least two affected members. Multipoint parametric and
      non-parametric linkage analyses were performed using MERLIN 1.1.1 and a
      susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9,
      p<0.0001; HLOD=3.3, alpha=0.7). The linked region harbours the functional
      candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach
      demonstrated disease association with variants in TRAK1.

PMID- 19837567
TI  - The effect of clozapine on regional cerebral blood flow and brain metabolite
      ratios in schizophrenia: relationship with treatment response.
AB  - The purpose of this study was to investigate the effect of clozapine on regional
      cerebral blood flow (rCBF) and its relationship with response to treatment. In
      addition, we aimed to study the influence of clozapine on proton magnetic
      resonance spectroscopy ((1)H-MRS) findings in the dorsolateral prefrontal cortex
      (DLPFC) in a subgroup of patients. Psychopathology, neurocognitive functioning,
      and SPECT imaging of 22 patients were assessed at the baseline and 8 weeks after
      the initiation of clozapine treatment. In 10 of these patients intermediate-echo
      (TE: 135 ms) single-voxel (1)H-MRS was also performed at the baseline and after 8
      weeks. Clozapine treatment increased the right frontal (superior and
      medial)/caudate perfusion ratio in the whole group, while it increased bilateral
      frontal (superior and medial)/caudate perfusion ratios in treatment responders.
      In addition, percentage changes in left and right frontal (superior and
      medial)/caudate perfusion ratios compared to the baseline were higher in
      treatment responders than in non-responders. The improvement in attention was
      related to the increase in percentage change in the right frontal (superior and
      medial)/caudate perfusion ratio, while the improvement in verbal fluency was
      related to the increase in percentage changes in both right and left frontal
      (superior and medial)/caudate perfusion ratios and to right frontal (superior and
      medial)/thalamus perfusion. Baseline frontal (superior and medial)/thalamus
      perfusion could explain 32% of the variability of percentage improvements in
      psychopathology. (1)H-MRS showed that the baseline PANSS general psychopathology
      score was inversely correlated with the baseline NAA/Cre ratio. An increased
      NAA/Cre ratio in DLPFC after 8 weeks of clozapine treatment was also revealed by
      (1)H-MRS. Our SPECT imaging results suggest the presence of an imbalance in
      fronto-striato-thalamic circuitry that changes with clozapine, especially in the
      responders, while (1)H-MRS results indicate a supportive effect of clozapine on
      neuronal integrity.

PMID- 19837568
TI  - Working memory and long-term memory deficits in schizophrenia: is there a common
      substrate?
AB  - Patients with schizophrenia exhibit substantial deficits in both working memory
      (WM) and long-term memory (LTM) tasks. While these two forms of memory are
      generally viewed as distinct, recent evidence from healthy subjects has
      challenged the robustness of the double-dissociation between these two types of
      memory. In light of an emerging view of WM and LTM as being subserved by a
      largely overlapping network of brain regions, it is possible that WM and LTM
      deficits in patients with schizophrenia share a common neurobiological substrate.
      This review revisits the functional neuroimaging literature on both WM and LTM in
      patients with schizophrenia with these considerations in mind, and reveals a
      number of commonalities in research findings in both literatures. While there is
      a paucity of direct evidence bearing on whether patient deficits in these tasks
      arise from a common functional abnormality, the available literature is
      consistent with the hypothesis that these deficits have the same origin.

PMID- 19837569
TI  - Evaluation of boronate-containing polymer brushes and gels as substrates for
      carbohydrate-mediated adhesion and cultivation of animal cells.
AB  - Boronate-containing thin polyacrylamide gels (B-Gel), polymer brushes (B-Brush)
      and chemisorbed organosilane layers (B-COSL) were prepared on the surface of
      glass slides and studied as substrates for carbohydrate-mediated cell adhesion. B
      COSL- and B-Brush-modified glass samples exhibited multiple submicron structures
      densely and irregularly distributed on the glass surface, as found by scanning
      electron microscopy and atomic force microscopy. B-Gel was ca. 0.1 mm thick and
      contained pores with effective size of 1-2 microm in the middle and of 5-20
      microm on the edges of the gel sample as found by confocal laser scanning
      microscopy. Evidence for the presence of phenylboronic acid in the samples was
      given by time-of-flight secondary ion mass-spectrometry (ToF SIMS), contact angle
      measurements performed in the presence of fructose, and staining with Alizarin
      Red S dye capable of formation specific, fluorescent complexes with boronic
      acids. A comparative study of adhesion and cultivation of animal cells on the
      above substrates was carried out using murine hybridoma M2139 cell line as a
      model. M2139 cells adhered to the substrates in the culture medium without
      glucose or sodium pyruvate at pH 8.0, and then were cultivated in the same medium
      at pH 7.2 for 4 days. It was found that the substrates of B-Brush type were
      superior both regarding cell adhesion and viability of the adhered cells, among
      the substrates studied. MTT assay confirmed proliferation of M2139 cells on B
      Brush substrates. Some cell adhesion was also registered in the macropores of B
      Gel substrate. The effects of surface microstructure of the boronate-containing
      polymers on cell adhesion are discussed. Transparent glass substrates grafted
      with boronate-containing copolymers offer good prospects for cell adhesion
      studies and development of cell-based assays.

PMID- 19837570
TI  - Bed types and cancer incidence.

PMID- 19837571
TI  - Disruption of MoCMK1, encoding a putative calcium/calmodulin-dependent kinase, in
      Magnaporthe oryzae.
AB  - Ca(2+) is a second messenger in pathways that transduce external signals and
      activate cellular processes in plants and animals. Ca(2+)-mediated signal
      transduction is involved in key pathways that contribute to a variety of
      fundamental physiological processes in eukaryotic cells. However, little is known
      about the molecular mechanisms of Ca(2+)-mediated signal transduction in
      filamentous fungi. In this study, the MoCMK1 gene, encoding a putative
      Ca(2+)/calmodulin-dependent kinase, was identified in the rice blast fungus
      Magnaporthe oryzae. Three MoCMK1 deletion mutants were obtained by a targeted
      gene replacement. Colonies of the MoCMK1 mutants had sparse aerial hyphae and
      fewer conidia than the wild-type strain on complete medium. Conidial germination
      and appressorial formation were delayed in the DeltaMocmk1 mutants. In spray
      inoculation tests, DeltaMocmk1 mutants exhibited a weakened ability to infect the
      susceptible rice cultivar CO-39, compared to the wild-type strain Guy11. These
      results showed that MoCMK1 plays key roles in the pathogenicity of the rice blast
      fungus.

PMID- 19837572
TI  - Detection of Thielaviopsis basicola in soil with real-time quantitative PCR
      assays.
AB  - Thielaviopsis basicola is a soil-borne fungus with a wide host range and a
      cosmopolitan distribution. It causes disease on many agricultural crops and in
      China it is the causal agent of black root rot on tobacco plant. Early diagnosis
      and detection of the pathogen in soil are critical to control this disease in
      field. The objective of this study was to develop sensitive and effective methods
      suitable for large-scale detection and quantification of T. basicola. Based on
      the nucleotide sequences of the internal transcribed spacer (ITS) regions of rDNA
      genes of Thielaviopsis spp, primers and TaqMan probe were designed specifically
      to amplify DNA from T. basicola and real-time, quantitative PCR (qPCR) assays
      were developed for rapid, specific and sensitive detection and quantification of
      T. basicola. It was sensitive with the detection limit of 100 fg microl(-1)
      genomic DNA of T. basicola in qPCR assays. By combining the qPCR assays with the
      efficient protocol to extract DNA from soil, it was possible to achieve real-time
      detection of T. basicola in soil in 4-5 h and the detection limit of 3 conidia
      per reaction in qPCR was recorded. The assays were applied to survey soils from
      tobacco fields in China for the presence of T. basicola and the analyses of
      naturally infested soil showed the reliability of the qPCR assays.

PMID- 19837573
TI  - Gender-specific fatty acid profiles in platelet phosphatidyl-choline and 
      ethanolamine.
AB  - Previous studies suggested that women synthesise docosahexaenoic acid (DHA) more
      efficiently from their precursors than men. This study investigated the
      relationship between diet, platelet phospholipids fatty acids and gender. Dietary
      intake and platelet phosphatidyl-choline (PC) and phosphatidylethanolamine (PE)
      fatty acids were determined in Caucasian 40 men and 34 women. Absolute and
      %energy intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and DHA,
      and the ratios of total n-6/n-3 PUFA and linoleic/alpha-linolenic acids did not
      differ between the sexes. However, women had higher DHA in PC (1.19 vs 1.05 wt%,
      p<0.05) and PE (3.62 vs 3.21 wt%, p<0.05) than men. Also EPA (1.10 vs 0.93 wt%,
      p<0.05) was higher in women's PE. Conversely, men had elevated AA and total n-6
      fatty acids in PC. The higher platelet DHA levels and lower platelet AA/EPA and
      AA/DHA ratios in women of child-bearing age compared with men, may lead to less
      platelet aggregation and vaso-occlusion.

PMID- 19837574
TI  - Are we ready to downregulate mast cells?
AB  - Downregulation of mast cells (MCs) function and/or survival is warranted in
      allergic inflammation (AI), mastocytosis/MC leukemias and in other inflammatory
      diseases in which MCs have a central role. Human MCs (hMCs) have been recently
      shown to express the death receptor (DR) TRAIL and the inhibitory receptors (IRs)
      CD300a and Siglec-8. TRAIL is the only known DR functional on hMCs, and
      interestingly its function is upregulated by IgE-dependent MC activation. The
      newly described IRs, CD300a and Siglec-8, potently downregulate MC activation and
      survival in vitro and inhibit different IgE-mediated responses in vivo. Therefore
      a selective targeting of TRAIL and of IRs on MC could be a novel
      immunopharmacological way to downregulate MC-associated diseases.

PMID- 19837575
TI  - Acute effects of NPPV in interstitial lung disease with chronic hypercapnic
      respiratory failure.
AB  - OBJECTIVE: A case series evaluating the acute effects of noninvasive positive
      pressure ventilation (NPPV) in patients with chronic hypercapnic respiratory
      failure (HRF) secondary to interstitial lung diseases (ILD). PATIENTS AND
      METHODS: Ten patients with ILD were retrospectively evaluated. All had
      restrictive lung function (mean TLC, 47.6+/-12.6% predicted) and chronic
      hypercapnic respiratory failure (mean pH=7.39+/-0.02). Arterial blood gas
      analysis and lung function were compared before and after the application of
      controlled pressure-limited NPPV. RESULTS: Daytime PaCO(2) during spontaneous
      breathing decreased by 5.4+/-1.3mmHg (95% confidence interval, 4.5-6.3), from
      57.7+/-5.1mmHg to 52.3+/-5.9 (p<0.001); while daytime PaO(2) increased by 3.4+/
      3.3mmHg (95% confidence interval, 1.0-5.8), from 63.7+/-3.5mmHg to 67.1+/-3.4
      (p=0.01); and TLC increased by 3.9+/-4.5% (95% confidence interval, 0.7-7.1),
      from 47.6+/-12.6%mmHg to 51.5+/-10.0% (p=0.023). CONCLUSIONS: In patients with
      ILD and chronic HRF controlled NPPV is tolerated and can acutely improve blood
      gas levels. Further studies examining the long-term benefits need to be explored.

PMID- 19837576
TI  - BK virus nephropathy: a pediatric nephrologist's perspective.
AB  - Polyomavirus (BK)-associated nephropathy (BKVN) is now recognized as significant
      problem in pediatric renal transplants that may lead to progressive allograft
      dysfunction. BKVN was first recognized in 1999 in adult renal transplant
      recipients, and most data have been obtained from this patient population. Today,
      there is an increasing number of publications pertaining to children with BKVN
      that allows for a selective analysis of the pediatric population. Most early
      pediatric publications were predominantly cases reports. However, several
      retrospective and prospective studies are now available that provide important
      insights with respect to the incidence of BKVN in the pediatric transplant
      population, the efficacy of treatment strategies, and the risk factors for
      developing BKVN. This review analyzes several of the most significant studies
      that address these issues.

PMID- 19837577
TI  - Mesophilic and thermophilic anaerobic biodegradability of water hyacinth pre
      treated at 80 degrees C.
AB  - Water hyacinth (Eichornia crassipes) is a fast growing aquatic plant which causes
      environmental problems in continental water bodies. Harvesting and handling this
      plant becomes an issue, and focus has been put on the research of treatment
      alternatives. Amongst others, energy production through biomethanation has been
      proposed. The aim of this study was to assess the anaerobic biodegradability of
      water hyacinth under mesophilic and thermophilic conditions. The effect of a
      thermal sludge pre-treatment at 80 degrees C was also evaluated. To this end,
      anaerobic biodegradability tests were carried out at 35 degrees C and 55 degrees
      C, with raw and pre-treated water hyacinth. According to the results, the thermal
      pre-treatment enhanced the solubilisation of water hyacinth (i.e. increase in the
      soluble to total chemical oxygen demand (COD)) from 4% to 12% after 30 min.
      However, no significant effect was observed on the methane yields (150-190 L
      CH(4)/kg volatile solids). Initial methane production rates for thermophilic
      treatments were two fold those of mesophilic ones (6-6.5L vs. 3-3.5 L CH(4)/kg
      COD x day). Thus, higher methane production rates might be expected from
      thermophilic reactors working at short retention times. The study of longer low
      temperature pre-treatments or pre-treatments at elevated temperatures coupled to
      thermophilic reactors should be considered in the future.

PMID- 19837578
TI  - Enzyme-mediated amperometric biosensors prepared via successive surface-initiated
      atom-transfer radical polymerization.
AB  - The development of enzyme-mediated amperometric biosensors on the indium-tin
      oxide (ITO) glass electrode via surface-initiated atom-transfer radical
      polymerization (ATRP) was investigated. A trichlorosilane coupling agent,
      containing the sulfonyl halide ATRP initiator, was immobilized initially on the
      ITO electrode surface for consecutive surface-initiated ATRP of ferrocenylmethyl
      methacrylate (FMMA) and glycidyl methacrylate (GMA). Glucose oxidase (GOD) was
      subsequently immobilized on the modified ITO electrode surface via coupling
      reactions between the epoxide groups of GMA and the amine groups of GOD. The
      surface composition after each functionalization step was ascertained by X-ray
      photoelectron spectroscopy (XPS). With the introduction of redox-P(FMMA) block as
      the electron-transfer mediator, the enzyme-mediated ITO electrode exhibits high
      sensitivity, as revealed by cyclic voltammetry measurement. The sensitivities of
      the ITO-g-P(GMA-GOD)-b-P(FMMA) and ITO-g-P(FMMA)-b-P(GMA-GOD) electrodes are
      about 3.6 microA/(mM cm(2)) (in the linear concentration range 0-5 mM of glucose)
      and 10.9 microA/(mM cm(2)) (in the linear concentration range of 0-17 mM of
      glucose), respectively. For both biosensors, the steady-state response time and
      the detection limits are estimated to be less than 20 s and 0.4+/-0.1 mM of
      glucose concentration, respectively. Furthermore, the spatial effect of the redox
      mediator on the electrode surface is revealed by the fact that the block
      copolymer brush-functionalized ITO electrode with P(FMMA) as the inner (first)
      block is more sensitive to glucose than that with P(GMA) as the inner block.

PMID- 19837579
TI  - Stem cells and liver repair.
AB  - The liver has considerable inherent regenerative capacity through hepatocyte
      division and hepatic progenitor cell proliferation. In chronic disease
      regeneration eventually fails and liver transplantation is the only curative
      treatment. Current work aims to restore liver mass and functionality either
      through transplantation of stem cell derived hepatocyte-like cells or by
      stimulating endogenous liver repair. Human embryonic stem cells (ESCs) and adult
      somatic cells can be differentiated into hepatocyte-like cells with potential use
      in drug testing, bio-artificial livers and transplantation. These cells still
      have some limitations in functionality, understanding further human liver
      development and improving tissue culture is required. The use of stem cells and
      their progeny in animal models of liver disease has been encouraging and
      stimulated clinical trials to commence.

PMID- 19837580
TI  - New strategies to generate induced pluripotent stem cells.
AB  - Direct reprogramming of somatic cells to a pluripotent state, substantiated only
      three years prior, is one of the most rapidly developing areas of stem cell
      research. The generation of patient-derived pluripotent cells applicable to
      disease modelling, drug screening, toxicology tests and, ultimately, autologous
      cell-based therapies, has the potential to revolutionize medicine. Since 2006,
      when Takahashi and Yamanaka first reported the generation of induced pluripotent
      stem cells from murine fibroblasts via retroviral transduction of a defined set
      of transcription factors, various new methods have been developed to refine and
      improve reprogramming technology. This review focus on these evolving strategies
      to generate genetically unmodified or reprogramming factor-free iPSCs.

PMID- 19837581
TI  - Microbial community structures in a horizontal biotrickling filter degrading H2S
      and NH3.
AB  - In this study, the temporal and spatial differences in the microbial community
      structures in a horizontal biotrickling filter (HBTF) for simultaneous
      biodegradation of H(2)S and NH(3) was investigated by denaturing gradient gel
      electrophoresis (DGGE) of polymerase chain reaction (PCR) amplified 16S rRNA gene
      fragments. Over 90% H(2)S and 95% NH(3) were removed simultaneously under the
      loadings up to 137gm(-3)h(-1) in most cases. PCR-DGGE fingerprints revealed high
      population diversity of the biofilm in the HBTF. The microbial community
      structures in the HBTF could adapt to changing operating conditions, e.g., inlet
      loadings and substrates starvation, while they were relatively stable under the
      constant loadings. In addition, the microbial community structures differed as a
      function of the section of the HBTF during early operational period, while they
      were much more similar over extended operation.

PMID- 19837582
TI  - High-level production of a thermoacidophilic beta-glucosidase from Penicillium
      citrinum YS40-5 by solid-state fermentation with rice bran.
AB  - A high yield of beta-glucosidase (EC 3.2.1.21) of 159.1 U/g-solid activity on 4
      nitrophenyl beta-d-glucopyranoside (pNPG) was achieved by rice bran-based solid
      state fermentation (SSF) of the recently characterized fungus Penicillium
      citrinum YS40-5. The enzyme was both thermophilic and acidophilic at the
      optimized temperature and pH of 70 degrees C and 5.0, respectively. Over 95% of
      the original beta-glucosidase activity was maintained after a prolonged storage
      at ambient temperature for 4 weeks. The kinetic parameters V(max), K(m) and K(I)
      were 85.93 U/mg, 1.2 mM and 17.59 mM with pNPG, and 72.49 U/mg, 32.17 mM and 8.29
      mM with cellobiose, respectively. The protein band with beta-glucosidase activity
      was characterized by native PAGE followed by MUG-zymogram analysis, and its
      identity confirmed by nanoLC-MS/MS. A 3.43-fold synergistic effect by combining
      this beta-glucosidase with Trichoderma reesei cellulases was observed, indicating
      this enzyme could potentially be used for improving the efficiency of cellulosic
      bioconversion.

PMID- 19837583
TI  - Energy saving achieved by limited filamentous bulking sludge under low dissolved
      oxygen.
AB  - Limited filamentous bulking caused by low dissolved oxygen (DO) was proposed to
      establish a low energy consumption wastewater treatment system. This method for
      energy saving was derived from two full-scale field observations, which showed
      pollutants removal would be enhanced and energy consumption could be reduced by
      at least 10% using limited filamentous bulking. Furthermore, preliminary
      investigation including the abundance evaluation and the identification of
      filamentous bacteria demonstrated that the limited filamentous bulking could be
      repeated steadily in a lab-scale anoxic-oxic reactor fed with domestic
      wastewater. The sludge loss did not occur in the secondary clarifier, while COD
      and total nitrogen removal efficiencies were improved by controlling DO for
      optimal filamentous bacterial population. Suspended solids in effluent were
      negligible and turbidity was lower than 2 NTU, which were distinctly lower than
      those under no bulking. Theoretical and experimental results indicated the
      aeration consumption could be saved by the application of limited filamentous
      bulking.

PMID- 19837584
TI  - Power plant intake quantification of wheat straw composition for 2nd generation
      bioethanol optimization--a Near Infrared Spectroscopy (NIRS) feasibility study.
AB  - Optimization of 2nd generation bioethanol production from wheat straw requires
      comprehensive knowledge of plant intake feedstock composition. Near Infrared
      Spectroscopy is evaluated as a potential method for instantaneous quantification
      of the salient fermentation wheat straw components: cellulose (glucan),
      hemicelluloses (xylan, arabinan), and lignin. Aiming at chemometric multivariate
      calibration, 44 pre-selected samples were subjected to spectroscopy and reference
      analysis. For glucan and xylan prediction accuracies (slope: 0.89, 0.94) and
      precisions (r(2): 0.87) were obtained, corresponding to error of prediction
      levels at 8-9%. Models for arabinan and lignin were marginally less good, and
      especially for lignin a further expansion of the feasibility dataset was deemed
      necessary. The results are related to significant influences from sub
      sampling/mass reduction errors in the laboratory regimen. A relative high
      proportion of outliers excluded from the present models (10-20%) may indicate
      that comminution sample preparation is most likely always needed. Different
      solutions to these issues are suggested.

PMID- 19837585
TI  - Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective
      inhibitors of cdc2-like kinases (Clk).
AB  - A series of substituted 6-arylquinazolin-4-amines were prepared and analyzed as
      inhibitors of Clk4. Synthesis, structure-activity relationships and the
      selectivity of a potent analogue against a panel of 402 kinases are presented.
      Inhibition of Clk4 by these agents at varied concentrations of assay substrates
      (ATP and receptor peptide) highly suggests that this chemotype is an ATP
      competitive inhibitor. Molecular docking provides further evidence that
      inhibition is the result of binding at the kinase hinge region. Selected
      compounds represent novel tools capable of potent and selective inhibition of
      Clk1, Clk4, and Dyrk1A.

PMID- 19837586
TI  - FLAG-tag selective covalent protein labeling via a binding-induced acyl-transfer
      reaction.
AB  - A FLAG tag selective protein labeling method is newly developed in this study.
      Coupling of the selective binding between synthetic Ni-complex probe and FLAG tag
      with the acyl transfer reaction enables the site-selective covalent modification
      of FLAG peptide and FLAG-tag fused protein.

PMID- 19837587
TI  - Use of ionically tagged glycosyl donors in the synthesis of oligosaccharide
      libraries.
AB  - We have developed a new procedure based on the random glycosyl reaction of a
      partially benzoylated glycosyl acceptor with a glycosyl donor containing a 4,6-O
      (4-methoxycarbonylbenzylidene) protecting group as a masked/caged ion-tag.
      Glycosylated products are ionically tagged by saponification of the methyl ester
      and the use of this anion-tag greatly simplifies the separation of the desired
      oligosaccharides from unreacted or excess glycosyl acceptors as well as from over
      glycosylated oligosaccharides. In addition, the use of partially benzoylated
      acceptors greatly improves their solubility in dichloromethane increasing the
      yield of product formation and, also, of altering the distribution of positional
      isomers in favor of products derived by reaction of the donors at hydroxyl groups
      which otherwise would be considerably less reactive. Using this new approach in
      random glycosyl reactions, several oligosaccharide libraries were readily
      prepared in overall yields of 60-70% and the individual positional isomers
      present in the libraries were identified using the 'reductive-cleavage' method.

PMID- 19837588
TI  - Novel 4-N-substituted aryl but-3-ene-1,2-dione derivatives of
      piperazinyloxazolidinones as antibacterial agents.
AB  - Novel (5S)-N-[3-(3-fluoro-4-{4-[2-oxo-4-(substituted aryl)-but-3-enoyl]-piperazin
      1-yl}-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 3a-j analogues were
      synthesized and their in vitro antibacterial activity was evaluated. Most of the
      compounds of series showed superior in vitro activity against Gram-positive
      resistant strains than linezolid. Compound 3f is the most potent compound in the
      series with 0.04-0.39 microg/mL MIC.

PMID- 19837589
TI  - Benzothiazoles as Rho-associated kinase (ROCK-II) inhibitors.
AB  - A series of benzothiazole derivatives as ROCK inhibitors have been discovered.
      Compounds with good biochemical and cellular potency, and sufficient kinase
      selectivity have been identified.

PMID- 19837590
TI  - Ephedrine therapy in eight patients with congenital myasthenic syndrome due to
      DOK7 mutations.
AB  - In congenital myasthenic syndrome with DOK7 mutations ephedrine was reported to
      be beneficial in single patients. We carried out a small, open and prospective
      cohort study in eight European patients manifesting from birth to 12 years. Five
      patients showed limb-girdle and facial weakness, three a floppy infant syndrome
      with bulbar symptoms and/or respiratory distress. Ephedrine was started with 25
      mg/day and slowly increased to 75-100 mg/day. Within weeks after starting therapy
      an improvement was observed in all patients and clinical follow-up disclosed
      positive effects more pronounced on proximal muscle weakness and strength using
      MRC scale. Effects on facial weakness were less pronounced. Vital capacity
      measurements and repetitive stimulation tests did not improve in the same way as
      clinical symptoms did. These investigations are appropriate to confirm the
      diagnosis in case of pathological results, but they might not be appropriate
      means to monitor patients under ephedrine therapy.

PMID- 19837591
TI  - Health-related quality of life of patients with epilepsy in Turkey.
AB  - The aim of this study was to measure the health related quality of life (HRQOL)
      of epilepsy patients and to compare it with that of a healthy control group. The
      evaluation included the effects of the type of seizure, duration of seizure and
      medical treatment on the quality of life of the patients. The group studied
      consisted of 221 participants (121 epilepsy patients and 100 healthy control
      individuals) who completed a sociodemographic data form and who were administered
      the World Health Organization Quality of Life (WHOQOL-100) scale. The epilepsy
      patients had statistically lower physical health, psychological well-being, level
      of independence and global HRQOL than participants in the control group (p<0.05).
      The analysis of variance showed that the partial epilepsy subgroup had
      significantly lower averages for all the quality-of-life subfields except for the
      social relationship dimension. On regression analysis, being married, having a
      generalized type of seizure and being treated with fewer medications were all
      related to higher scores on the HRQOL. Epilepsy is a disease that has
      neurological, psychiatric and psychosocial dimensions that should be evaluated
      using a multidisciplinary approach.

PMID- 19837592
TI  - Protein-protein interaction networks: how can a hub protein bind so many
      different partners?
AB  - How can a single hub protein bind so many different partners? Numerous studies
      have sought differences between hubs and non-hubs to explain what makes a protein
      a hub and how a shared hub-binding site can be promiscuous, yet at the same time
      be specific. Here, we suggest that the problem is largely non-existent and
      resides in the popular representation of protein interaction networks: protein
      products derived from a single gene, even if different, are clustered in maps
      into a single node. This leads to the impression that a single protein binds to a
      very large number of partners. In reality, it does not; rather, protein networks
      reflect the combination of multiple proteins, each with a distinct conformation.

PMID- 19837593
TI  - Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part
      1: synthesis and biological evaluation of antivascular activity.
AB  - The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and
      possesses potent anticancer activity. Various chalcone analogues were synthesized
      and evaluated for their cell growth inhibitory properties against the K562 human
      chronic myelogenous leukemia cell line (SD400, IC(50) 0.21nM; combretastatin A4
      CA4, IC(50) 2.0nM). Cell cycle analysis by flow cytometry indicated that these
      agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%).
      They inhibit tubulin assembly at low concentration (SD400, IC(50) 0.46microM;
      CA4, 0.10microM) and compete with [(3)H]colchicine for binding to tubulin (8%
      [(3)H]colchicine remained bound to tubulin after competition with SD400 or CA4).
      Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC
      cells, consistent with vasculature damaging activity.

PMID- 19837594
TI  - Combretastatin-like chalcones as inhibitors of microtubule polymerisation. Part
      2: Structure-based discovery of alpha-aryl chalcones.
AB  - Tubulin is an important molecular target in cancer chemotherapy. Antimitotic
      agents able to bind to the protein are currently under study, commonly used in
      the clinic to treat a variety of cancers and/or exploited as probes to
      investigate the protein's structure and function. Here we report the binding
      modes for a series of colchicinoids, combretastatin A4 and chalcones established
      from docking studies carried out on the structure of tubulin in complex with
      colchicine. The proposed models, in agreement with published biochemical data,
      show that combretastatin A4 binds to the colchicine site of beta-tubulin and that
      chalcones assume an orientation similar to that of podophyllotoxin. The models
      can be used to design a new class of podophyllotoxin mimics, the alpha-aryl
      chalcones, capable of binding to the colchicine-binding site of beta-tubulin with
      higher affinity.

PMID- 19837595
TI  - Synthesis of bis-Schiff bases of isatins and their antiglycation activity.
AB  - Bis-Schiff bases 1-27 have been synthesized and their in vitro antiglycation
      potential has been evaluated. Compounds 21 (IC(50)=243.95+/-4.59microM), 20
      (IC(50)=257.61+/-5.63microM), and 7 (IC(50)=291.14+/-2.53microM) showed an
      excellent antiglycation activity better than the standard (rutin, IC(50)=294.46+/
      1.50microM). This study has identified a series of potential molecules as
      antiglycation agents. A structure-activity relationship has been studied, and all
      the compounds were characterized by spectroscopic techniques.

PMID- 19837596
TI  - The lifespan-promoting effect of acetic acid and Reishi polysaccharide.
AB  - Using Caenorhabditis elegans as a model organism, various natural substances and
      commercial health-food supplements were screened to evaluate their effects on
      longevity. Among the substances tested, acetic acid and Reishi polysaccharide
      fraction 3 (RF3) were shown to increase the expression of the lifespan and
      longevity-related transcription factor DAF-16 in C. elegans. We have shown that
      RF3 activates DAF-16 expression via TIR-1 receptor and MAPK pathway whereas
      acetic acid inhibits the trans-membrane receptor DAF-2 of the insulin/IGF-1
      pathway to indirectly activate DAF-16 expression. In addition, a mixture of
      acetic acid and RF3 possesses a combined effect 30-40% greater than either
      substance used alone. A proteomic analysis of C. elegans using 2-DE and LC-MS/MS
      was then carried out, and 15 differentially expressed proteins involved in the
      lifespan-promoting activity were identified.

PMID- 19837598
TI  - Effects of alpha particles on zebrafish embryos.
AB  - Dechorionated zebrafish embryos were irradiated at 1.5 h post fertilization (hpf)
      to low-doses of alpha particles, viz., 1.4, 2.8, 5.6, 11.2 mGy (determined using
      Monte Carlo simulations). At 24 hpf, these embryos were then examined for
      apoptotic cells through acridine orange staining. The mean number of apoptotic
      cells was found to decrease significantly from controls to 1.4-mGy irradiation,
      and then to increase almost linearly to 2.8, 5.6 and 11.2-mGy irradiation. This
      trend is a typical characteristic of a hormetic effect.

PMID- 19837599
TI  - Research of online automatic titanium grade analyzer and method based on energy
      dispersive X-ray fluorescence technology.
AB  - An online automatic Ti-grade analyzer (OATGA), consisting of a (238)Pu source and
      a proportional counter, is designed for assuring product quality. The advantage
      of this system was its time-effectiveness; the entire monitoring process can be
      finished within approximately 5 min. This system has successfully solved some key
      analysis issues in titanium ore concentrate production process. The results
      obtained by feature measurements and chemical analysis were in agreement with
      each other. After two-year usage of OATGA at PANGANG, southwestern China, it was
      proved as a reliable method for online quality control in the production process
      of titanium ore concentrate.

PMID- 19837600
TI  - A new 2-dimensional method for constructing visualized treatment objectives for
      distraction osteogenesis of the short mandible.
AB  - Open bite development during distraction of the mandible is common and partly due
      to inaccurate planning of the treatment. Conflicting guidelines exist in the
      literature. A method for Visualized Treatment Objective (VTO) construction is
      presented as an aid for determining the correct orientation of monodirectional
      and multidirectional distractors. Distraction on the left and on the right side
      of the mandible takes place in a parallel manner in order to maintain
      intercondylar width. It follows that in the absence of marked asymmetry, the
      amount of mandibular body distraction, the amount of ramus distraction and
      (should it apply), the amount of closure of the gonial angle, can be derived from
      a simple 2-dimensional plan. After presurgical orthodontic treatment, a
      cephalogram is taken and a VTO is constructed, that aims at a good occlusion with
      the enhanced mandible in centric relation, with little or no change of the
      original position of the rami.

PMID- 19837601
TI  - Optimizing the management of metastatic colorectal cancer.
AB  - The prognosis of patients with metastatic colorectal cancer has significantly
      improved in the last few years, with the introduction into the clinical practice
      of new cytotoxic treatments, the availability of non-cross resistant agents after
      the front-line treatment failure, and the combination of targeted agents (i.e.,
      the inhibitors of the epidermal growth factor and vascular endothelial growth
      factor pathways) with conventional drugs. All these options must be incorporated
      into a complex strategy of management, in which a customized management according
      to the disease status, with an intensified induction approach followed by
      maintenance (and reinduction), should be investigated.

PMID- 19837602
TI  - Challenging estrogen receptor beta with phosphorylation.
AB  - From classical gland-based endocrinology to nuclear hormone receptor biology,
      tremendous progress has been made in our understanding of hormone responses
      underlying cellular communication. Estrogen elicits a myriad of biological
      processes in reproductive and peripheral target tissues through its interaction
      with the estrogen receptors ERalpha and ERbeta. However, our knowledge of
      estrogen-dependent and independent action has mainly focused on ERalpha, leaving
      the role of ERbeta obscure. This review discusses our current understanding of
      ERbeta function and the emerging role of intracellular signals that act upon and
      achieve estrogen-like effects through phosphorylation of ERbeta protein.
      Improving our understanding of how cellular determinants impact estrogen receptor
      actions will likely lead to treatment strategies for related endocrine diseases
      affecting women's health.

PMID- 19837603
TI  - Sex steroids and the male skeleton: a tale of two hormones.
AB  - Traditionally, the stronger male skeleton was considered to result from higher
      androgen levels in men compared to women. However, the regulation of male bone
      growth by sex steroids appears more complex than originally anticipated. Based on
      clinical observations and studies in animal models, not only androgens and
      androgen receptor (AR), but also estrogens and estrogen receptor-alpha (not
      ERbeta) are required for optimal bone mineral acquisition during male growth. In
      addition, both sex steroids are involved in the maintenance of male skeletal
      health. In fact, bone loss and fracture risk have been associated with estrogen
      exposure in elderly men. Overall, a compelling body of evidence suggests that
      both androgens and estrogens are crucial for male skeletal growth and
      maintenance.

PMID- 19837604
TI  - Estimation of handgrip force using frequency-band technique during fatiguing
      muscle contraction.
AB  - In this paper, we propose a force estimation model to compute the handgrip force
      from SEMG signal during fatiguing muscle contraction tasks. The appropriate
      frequency range was analyzed using various combinations of a wavelet scale, and
      the highest accuracy was achieved at a range from 242 to 365 Hz. After that,
      eight healthy individuals performed a series of static (70%, 50%, 30%, and 20%
      MVC) and dynamic (0-50% MVC) muscle contraction tasks to evaluate the performance
      of this technique in comparison with that of former method using the Root Mean
      Square of the SEMG signal. Both methods had comparable results at the beginning
      of the experiments, before the onset of muscle fatigue. However, differences were
      clearly observed as the degree of muscle fatigue began to increase toward the
      endurance time. Under this condition, the estimated handgrip force using the
      proposed method improved from 17% to 134% for static contraction tasks and 40%
      for dynamic contraction tasks. This study overcomes the limitation of the former
      method during fatiguing muscle contraction tasks and, therefore, unlocks the
      potential of utilizing the SEMG signal as an indirect force estimation method for
      various applications.

PMID- 19837605
TI  - Long-term outcome after bare-metal or drug-eluting stenting for allograft
      coronary artery disease.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) with bare-metal stenting
      (BMS) has been reported to be associated with high rates of target-lesion
      revascularization (TLR) in heart transplant recipients. We aimed to assess the
      outcome of successful PCI with BMS or drug-eluting stenting (DES) in such
      patients. METHODS: Ninety-four consecutive heart transplant recipients with
      successful PCI of de novo lesions with BMS (n = 53) or DES (n = 60) were
      prospectively followed-up for 3.7 +/- 2.5 years after PCI. An angiographic lesion
      based analysis at 12-month follow-up and a long-term, patient-based survival
      analysis were performed. RESULTS: The lesion-based analysis within 12 months
      after PCI showed a reduction of TLR rates with the use of DES (6.6% vs 26.4%, p <
      0.01). DES were associated with better preservation of left ventricular function
      at this time-point. The patient-based, long-term analysis showed sustained local
      benefit of DES (hazard ratio 4.5 [1.4 to 14.5] for BMS vs DES), but no effect on
      mortality, remote-site PCI and total revascularization rates. Anti-hypertensive
      (hazard ratio 0.2 [0.1 to 0.5]) and aspirin (hazard ratio 0.3 [0.1 to 0.8])
      therapy, and left ventricular ejection fraction (0.96 [0.94 to 0.98] per percent)
      were the only correlates of long-term mortality. CONCLUSIONS: Compared with BMS,
      DES are associated with a sustained reduction in rates of TLR and could safely be
      used in heart transplant recipients with coronary artery disease. Despite
      excellent local effects, DES use failed to reduce mortality. Anti-hypertensive
      and anti-platelet therapy, and left ventricular function preservation, may be
      considered as aims of treatment to improve long-term survival in such patients.

PMID- 19837606
TI  - Pulmonary hypertension in heart transplantation: discrepant prognostic impact of
      pre-operative compared with 1-year post-operative right heart hemodynamics.
AB  - BACKGROUND: The prognostic impact of pulmonary hypertension (PH) before and after
      heart transplantation (HTx) is debated. We investigated: (i) the significance of
      pre-operative reversible PH on post-operative survival; (ii) the value of
      recatheterization while on the waiting list; (iii) the evolution of right heart
      hemodynamics (RHH) after HTx; and (iv) the prognostic impact of PH at 1 year
      after HTx. METHODS: We reviewed the records of 500 HTx recipients transplanted
      between 1983 and 2007. Pre-operatively, a non-PH group (Group 1, n = 365)
      fulfilled directly our RHH criteria for HTx, while a PH group (Group 2, n = 135)
      was accepted after reversibility of PH by acute vasodilatory testing.
      Recatheterization was performed every third month while on the waiting list and
      repeatedly after transplantation. RESULTS: With a follow-up of 6.8 +/- 5.1 years
      and a 50% survival rate of 12.1 +/- 5.4 years, our main findings were as follows:
      (i) Patients with reversible PH on vasodilatory testing had a survival rate
      similar to that of patients without PH (11.7 +/- 0.8 vs 12.1 +/- 0.5 years, p =
      0.80). (ii) Pre-operative recatheterization was of limited value as RHH remained
      stable. Five percent of patients died while on the waiting list and 2 improved
      clinically and were removed. (iii) Mean pulmonary artery pressure (MAP) was
      reduced from 28 +/- 9 and 40 +/- 8 mm Hg pre-operatively to 21 +/- 7 and 24 +/- 6
      mm Hg after 2 weeks and 16 +/- 7 and 18 +/- 8 mm Hg at 3 years in Groups 1 and 2,
      respectively. (iv) Recipients with MAP >20 mm Hg at 1 year post-HTx had
      significantly lower survival than those with MAP <or=20 mm Hg (11.5 +/- 0.7 vs
      15.6 +/- 0.6 years, p < 0.001). CONCLUSIONS: Elevated pulmonary pressure 1 year
      after HTx provides significant prognostic information regarding long-term
      outcome, whereas pre-operative reversible PH in this group does not influence
      survival.

PMID- 19837608
TI  - Body mass, chronic heart failure, surgery and survival.
AB  - Cardiac cachexia, associated with excessive activation of the sympathetic nervous
      system together with immune activation, is an important prognostic indicator in
      heart failure. Anecdotally, the prevalence of cardiac cachexia appears to be
      falling, perhaps due to the increased use of beta-blockers. However, chronic
      heart failure is so common that many patients continue to lose weight and
      continue to deteriorate to a point where transplantation or mechanical support is
      considered. The origin of cachexia remains elusive and further research is needed
      to explore the relation between weight, sympathetic activation, and the response
      to cardiac surgery or transplantation.

PMID- 19837607
TI  - Quality of life and functional status in patients surviving 12 months after left
      ventricular assist device implantation.
AB  - BACKGROUND: As left ventricular assist device (LVAD) support duration increases,
      quality of life (QoL) becomes a concern. We reviewed the QoL in patients on LVAD
      support for >or=1 year. METHODS: We retrospectively reviewed our prospective
      database for patients supported >or=1 year by HeartMate pulsatile- (HM1) or
      continuous-flow (HM2) LVADs from 2000 to 2009. Transplant or death before 1 year
      merited exclusion. Metabolic equivalents of tasks (METs), the Minnesota Living
      with Heart Failure Questionnaire (MLHFQ), the 6-minute walk distance (6MWD), and
      New York Heart Association (NYHA) class were reviewed. Complications and re
      admissions were assessed. RESULTS: Thirty patients were supported for >or=1 year
      (7 HM1s, 23 HM2s). Mean support duration was 594 +/- 173 days. Mean QoL
      metrics/functional status indicators at 12 months were: 6MWD, 393 +/- 290 m; MET
      tolerance, 3.3 +/- 1; MLHFQ, 35 +/- 31; and NYHA, 1.4 +/- 0.6. Mean re
      admissions/year was 2.9 +/- 2, with a duration of 13.8 +/- 21 days. Three
      patients were never re-admitted. Mean out-of-hospital time was 471 +/- 172 days
      (87.3% of days). Infectious complications led to 43% of re-admissions and
      occurred in the: drive-line (47%) at 442 +/- 236 days; blood (37%) at 472 +/- 257
      days; and LVAD pocket (20%) at 550 +/- 202 days. Twenty-three patients (77%)
      required additional operations (1.7 +/- 1.8/year). The most common indication was
      drive-line infection, but ranged from ischemic bowel to defibrillator exchange.
      Eight required LVAD exchanges for mechanical (n = 4), electrical (n = 3), and
      thrombotic (n = 1) issues. CONCLUSIONS: Although LVAD support is not without
      complications, patients spend the majority of time outside the hospital enjoying
      a good quality of life.

PMID- 19837609
TI  - Initial experience with CentriMag extracorporal membrane oxygenation for support
      of critically ill patients with refractory cardiogenic shock.
AB  - BACKGROUND: Cardiogenic shock refractory to conventional therapy has very high
      mortality and limited support options. New technology with peripherally inserted
      CentriMag (Levitronix LLC, Waltham, MA) extracorporal membrane oxygenation (ECMO)
      may have the potential to significantly improve survival in these critically ill
      patients. Outcomes of the first 10 patients to receive this device at our
      institutions are presented. METHODS: Patients were identified by their primary
      physicians and evaluated by our Mechanical Circulatory Support Team. CentriMag
      ECMO was initiated at the bedside using sterile percutaneous cannulation of
      femoral vessels. Patients were admitted to the Heart and Vascular Intensive Care
      Unit, with care managed by regular nursing staff with special training. RESULTS:
      The patients (5 men, 5 women) were a mean age of 45 +/- 18 years, had a mean left
      ventricular ejection fraction of 30%, and a mean lactate level of 9 mmol/liter.
      All patients met criteria for shock refractory to medical therapy, but the
      etiology varied. Average duration of ECMO support was 5.8 +/- 4 days. Survival
      was 60%. There were no major complications directly related to the device and no
      equipment malfunctions. CONCLUSIONS: The peripherally inserted CentriMag ECMO was
      easy to insert, functioned without mechanical error, and significantly reduced
      expected mortality in critically ill patients. Further research will be necessary
      to develop standardized algorithms and gain more experience, but this new
      technology has promising potential.

PMID- 19837610
TI  - Ventricular unloading is associated with increased 20s proteasome protein
      expression in the myocardium.
AB  - BACKGROUND: The ubiquitin-proteasome system (UPS) breaks down misfolded and
      normal proteins, including cell cycle regulatory proteins involved in cardiac
      hypertrophy. Because congestive heart failure (CHF) increases cardiomyocyte
      cellular mass, indicative of increased protein synthesis and/or impaired
      breakdown, and ventricular unloading decreases cardiac hypertrophy and changes
      regulation of multiple molecular systems ("reverse cardiac remodeling"), we
      tested the hypothesis that ventricular unloading alters myocardial UPS. METHODS:
      In 23 paired myocardial specimens (before and after unloading) ubiquitin, 20S
      proteasome, and cyclin D1 were investigated immunohistochemically and
      morphometrically quantified in relation to cardiomyocyte hypertrophy, DNA
      content, nuclear profile area and perimeter, and cyclin D1 protein expression.
      Moreover, 20S proteasome plasma concentrations were measured by enzyme-linked
      immunoassay (ELISA). RESULTS: In CHF, sarcoplasmic 20S proteasome protein
      expression was significantly decreased compared with controls, but significantly
      increased after unloading. In contrast, sarcoplasmic ubiquitin protein was
      increased in CHF but significantly decreased after unloading, and both variables
      were inversely correlated. Cardiomyocyte 20S proteasome expression correlated
      inversely with cell size, mean DNA content, and cyclin D1, whereas ubiquitin
      protein expression was positively correlated with these parameters. The 20S
      proteasome plasma concentration was significantly increased after unloading.
      CONCLUSIONS: Our data indicate that: (1) the UPS is depressed in CHF; and (2)
      this is reversed by ventricular unloading and associated with decreased
      cardiomyocyte hypertrophy, mean DNA content, and cell cycle regulatory proteins.
      The findings support the view that the UPS is involved in both the pathogenesis
      of cardiac hypertrophy and "reverse cardiac remodeling" after ventricular
      unloading.

PMID- 19837611
TI  - Low incidence of severe respiratory syncytial virus infections in lung transplant
      recipients despite the absence of specific therapy.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infections in lung transplant
      recipients (LTRs) have been associated with significant morbidity and mortality.
      Immunoglobulins, ribavirin, and palivizumab are suggested treatments for both pre
      emptive and therapeutic purposes. However, in the absence of randomized, placebo
      controlled trials, efficacy is controversial and there is toxicity as well as
      cost concerns. METHODS: We retrospectively reviewed cases of lower respiratory
      tract RSV infections in adult LTRs. Diagnosis was based on clinical history,
      combined with a positive polymerase chain reaction (PCR) and/or viral cultures of
      bronchoalveolar lavage (BAL) specimens. RESULTS: Ten symptomatic patients were
      identified (7 men and 3 women, age range 28 to 64 years). All were hospitalized
      for community-acquired respiratory tract infections. Two patients had a
      concomitant acute Grade A3 graft rejection, and 1 patient had a concomitant
      bacterial pneumonia. Eight patients did not receive a specific anti-RSV treatment
      because of clinical stability and/or improvement at the time of RSV diagnosis.
      Only 2 patients (1 with Grade A3 allograft rejection and 1 requiring mechanical
      ventilation) received ribavirin and palivizumab. All patients recovered without
      complications and with no persistent RSV infection. However, bronchiolitis
      obliterans (BOS) staging worsened in 6 patients during the mean follow-up of 45
      months. CONCLUSIONS: Our data suggest that mild RSV infections in LTRs might
      evolve favorably in the absence of specific anti-viral therapy. However, this
      observation needs confirmation in a large clinical trial specifically
      investigating the development of BOS in untreated vs treated patients.

PMID- 19837612
TI  - Turning the process-dissociation procedure inside-out: a new technique for
      understanding the relation between conscious and unconscious influences.
AB  - While there is now general agreement that memory gives rise to both conscious and
      unconscious influences, there remains disagreement concerning the process
      architecture underlying these distinct influences. Do they arise from independent
      underlying systems (e.g., Jacoby, 1991) or from systems that are interactive
      (e.g., Joordens & Merikle, 1993)? In the current paper we present a novel "inside
      out" technique that can be used with the process-dissociation paradigm to arrive
      at more concrete conclusions concerning this central question and demonstrate
      this technique via a meta-analysis of currently published findings. Our results
      suggest that the data presented in these studies vary in ways most consistent
      with the assumption that conscious and unconscious influences behave
      independently.

PMID- 19837613
TI  - The outcome of examination (manipulation) under anesthesia on the stiff elbow
      after surgical contracture release.
AB  - HYPOTHESIS: We have used a technique of elbow examination under anesthesia in
      select patients after surgical release to assess the smoothness of the
      articulation, evaluate stability, and to stretch the flexion and rotation arcs.
      MATERIALS AND METHODS: The study comprised 51 consecutive patients who underwent
      an examination under anesthesia between January of 1996 and December of 2001.
      RESULTS: The examination occurred a mean of 40 days after surgery. Forty-four
      patients with a minimum of 12 months follow-up revealed a mean pre-examination
      arc of 33 degrees , which improved to 73 degrees at the final assessment. Three
      patients had no appreciable change (<10 degrees ) in the total arc, and 1 patient
      lost motion. Four patients underwent a second examination under anesthesia at a
      mean of 119 days after the first examination. The average pre-examination arc of
      40 degrees increased to 78 degrees at the final assessment (mean improvement, 38
      degrees ). The only complication was worsening of ulnar paresthesias in 3; with 2
      resolving spontaneously, and 1 patient requiring anterior ulnar nerve
      transposition. CONCLUSIONS: Examination (manipulation) under anesthesia can be a
      valuable adjunctive procedure to help regain the motion obtained at the time of
      surgical release. Because this was not a controlled series, additional studies
      might be conducted to refine those not benefiting from this procedure. In our
      series no permanent complications were noted.

PMID- 19837614
TI  - Clinical and pathologic predictors of Gleason sum upgrading in patients after
      radical prostatectomy: results from a single institution series.
AB  - OBJECTIVES: Preoperative Gleason scores (GSs) are often upgraded after pathologic
      examination of the prostate following radical prostatectomy (RP). There have been
      disparate reports of the impact of different factors as predictors of GS
      upgrading after RP. We sought to study the robustness of frequently reported
      predictors in an unselected single institution cohort. PATIENTS AND METHODS: A
      total of 684 patients with biopsy-proven prostate cancer treated with RP between
      2004 and 2007 were included in the study. The association between clinical and
      pathologic parameters and GS upgrading was retrospectively evaluated. Logistic
      regression analysis was used to identify predictors of pathologic grading
      changes. Likelihood of upgrading was compared between tertile groups for prostate
      volume and prostate-specific antigen (PSA) density using chi(2) analysis and
      multivariate logistic regression. Pathologic outcomes were compared between cases
      with and without GS upgrading. RESULTS: The overall mean age was 64.3 years, with
      median PSA level of 7.04 ng/ml. Overall, 203 cases (29.7%) were upgraded, whereas
      481 patients (70.3%) were downgraded or had identical biopsy and pathologic GS
      after RP. Patients with prostate volume of <31 g were upgraded in 32.6% of the
      cases compared with 21.9% in patients with prostate volume of >45 g (P = 0.020).
      On multivariate analysis preoperative PSA (P < 0.0001), prostate volume (P <
      0.0001), and PSA density (P < 0.0001) were predictive of Gleason sum upgrading.
      Upgraded patients were more likely to have extracapsular extension, seminal
      vesicle invasion, positive surgical margins, and lymphonodular invasion at RP (P
      < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSIONS: Smaller
      prostate volume and higher PSA level are associated with clinically significant
      upgrading of GS. PSA density as a function of both is a significant predictor of
      GS upgrading in low- and high-risk patients. This may be of relevance in the
      pretreatment risk assessment of prostate cancer patients.

PMID- 19837615
TI  - Laparoscopic mesh herniorrhaphy: impact on outcomes associated with radical
      retropubic prostatectomy.
AB  - OBJECTIVES: Laparoscopic herniorrhaphy employing non-absorbable mesh (LMH) is a
      frequently performed procedure for groin hernia. Multiple case reports in the
      urologic literature have identified LMH as a complicating factor in patients
      undergoing open radical retropubic prostatectomy (RRP) for prostate cancer. The
      purpose of this study was to review our experience and outcomes in patients with
      a prior LMH undergoing open RRP. METHODS: After institutional review board
      approval, a retrospective review of all open RRPs performed by a single surgeon
      between 2003 and 2008 was used to identify patients with a history of a prior
      LMH. The outcomes of these patients were compared with a contemporary cohort of
      patients undergoing RRP by the same surgeon. RESULTS: Eighteen patients with a
      prior LMH underwent RRP. Five of the 18 had bilateral LMH, with unilateral LMH in
      the remainder. Outcomes in this group were compared with 38 patients without
      prior LMH. There was no difference between the groups in terms of age,
      preoperative PSA, prostate size, preoperative Gleason score, or body mass index,
      and RRP was successfully performed in all 18 LMH patients. One of 18 patients had
      a postoperative complication (persistent JP drainage). Compared with the control
      group, differences in operative time and blood loss bordered on statistical
      significance. CONCLUSIONS: Prior LMH is not a contraindication to RRP. While
      resulting in slightly longer operating times and higher blood loss, our
      experience suggests that RRP can be safely performed in these patients.

PMID- 19837616
TI  - A disproportion of TH1/TH2 cytokines with predominance of TH2, in urothelial
      carcinoma of bladder.
AB  - OBJECTIVES: Bladder cancer is a common tumor of the urinary tract, accounting for
      6% to 8% of all male malignancies and 2% to 3% of all female malignancies.
      Urothelial carcinoma (UC) of bladder is the second most common urologic
      malignancy after prostate cancer. Earlier report has elucidated immunologic
      unreactivity in cancer patients. Cytokines play a pivotal role in the induction
      of cell mediated and humoral immunity. Quantification of cytokine response in
      cancer patients can give significant insights about the cellular immunologic
      potency against the neoplastic cells. In the present study, we aimed to assess
      alterations of Th1 and Th2 derived cytokines in progression of UC of bladder by
      determining their circulatory concentration in bladder cancer patients and
      healthy controls and to correlate the observations with grade and severity of the
      disease. MATERIALS AND METHODS: The study cohort consisted of 122 subjects; 72
      patients with bladder UC (28, low grade; 17, high grade; 27, muscle invasive) and
      50 healthy controls. The circulatory levels of various cytokines were measured
      using commercially available sandwich enzyme linked immunosorbent assay (ELISA)
      kit from BD Biosciences, San Diego, CA, and were statistically correlated
      according to the grade and the severity of disease. RESULTS: The serum levels of
      typical Th1 cytokines: IL-2 and IFN-gamma were found to be significantly lower (P
      < 0.001) while levels of Th2 cytokines i.e., IL-4, IL-5, and IL-10 were
      significantly higher (P < 0.001) in patients than in controls. The levels of all
      the cytokines were correlated with the grade and severity of the disease. There
      were significant differences between the patients with low grade tumors and
      muscle invasive tumors for all cytokines (P < 0.001); except IL-10 (P < 0.626).
      CONCLUSIONS: The results of our study delineate that in bladder tumor patients a
      marked polarization exists towards the expression of Th2 type cytokines while Th1
      remain suppressed. Furthermore, the levels of all the cytokines alter according
      to the grades of the tumor. This can give significant insights about the use of
      Th1 type cytokines for the administration of immunotherapy to bladder cancer
      patients. Development of new strategies attempting to manipulate the equilibrium
      between Th1 and Th2 cells would be beneficial in the management of UC of bladder
      in future.

PMID- 19837617
TI  - Comparison of prostate cancer tumor volume and percent cancer in prediction of
      biochemical recurrence and cancer specific survival.
AB  - OBJECTIVES: Tumor volume and percent cancer (ratio of tumor volume/prostate
      volume) have been proposed as predictors of biochemical recurrence and cancer
      specific survival after radical prostatectomy. However, their relative merits as
      prognosticators have not been tested. We therefore evaluated and compared tumor
      volume and percent cancer as independent predictors of biochemical recurrence and
      prostate cancer specific death after radical prostatectomy. METHODS AND
      MATERIALS: A retrospective review of 739 patients who underwent radical
      prostatectomy for prostate cancer between 1984 and 2004 was conducted. Median
      follow-up was 91.7 months, and 22 patients died of prostate cancer. Univariate
      and multivariate analysis evaluated the following factors in predicting
      biochemical recurrence and prostate cancer specific death: tumor volume, prostate
      volume, percent cancer, Gleason score, percentage of Gleason grade 4/5, margin
      status, capsular invasion status, seminal vesicle invasion status, preoperative
      PSA, and lymph node status. RESULTS: In univariate analysis, both tumor volume
      (P<0.001) and percent cancer (P<0.001) significantly correlated with biochemical
      recurrence. Since they are highly correlated, they did not predict outcome
      independently when included in the same model; however, both were highly
      predictive for biochemical recurrence in separate multivariate models (P=0.01 for
      both). Both also correlated with cancer specific survival as single variables;
      however, in separate multivariate models, only tumor volume (P=0.03) predicted
      death, while percent cancer did not (P=0.09). CONCLUSIONS: Tumor volume and
      percent cancer are independent predictors of recurrence after radical
      prostatectomy. However, in our series, tumor volume predicted cancer specific
      death better than percent cancer. Therefore, accurate determination of tumor
      volume, along with other accepted pathologic indices, is sufficient and preferred
      over percent cancer for prognostication after radical prostatectomy.

PMID- 19837618
TI  - A new gold standard for varicose vein treatment?

PMID- 19837619
TI  - Analysis of malaria associated genetic traits in Cabo Verde, a melting pot of
      European and sub Saharan settlers.
AB  - Malaria has occurred in the Cabo Verde archipelago with epidemic characteristics
      since its colonization. Nowadays, it occurs in Santiago Island alone and though
      prophylaxis is not recommended by the World Health Organization, studies have
      highlight the prospect of malaria becoming a serious public health problem as a
      result of the presence of antimalarial drug resistance associated with mutations
      in the parasite populations and underscore the need for tighter surveillance.
      Despite the presumptive weak immune status of the population, severe symptoms of
      malaria are not observed and many people present a subclinical course of the
      disease. No data on the prevalence of sickle-cell trait and red cell glucose-6
      phosphate dehydrogenase deficiency (two classical genetic factors associated with
      resistance to severe malaria) were available for the Cabo Verde archipelago and,
      therefore, we studied the low morbidity from malaria in relation to the
      particular genetic characteristics of the human host population. We also included
      the analysis of the pyruvate kinase deficiency associated gene, reported as
      putatively associated with resistance to the disease. Allelic frequencies of the
      polymorphisms examined are closer to European than to African populations and no
      malaria selection signatures were found. No association was found between the
      analyzed human factors and infection but one result is of high interest: a
      linkage disequilibrium test revealed an association of distant loci in the PKLR
      gene and adjacent regions, only in non-infected individuals. This could mean a
      more conserved gene region selected in association to protection against the
      infection and/or the disease.

PMID- 19837620
TI  - Bilateral ovarian serous borderline tumor with a giant non-invasive peritoneal
      implant in a four-year-old girl.
AB  - Epithelial ovarian tumors are uncommon before 20 years of age and rarely occur
      before puberty. The vast majority of these tumors are benign, and few cases of
      malignant and borderline tumors are described. We report a case of a 4-year-old
      premenarchal girl, previously healthy, who presented with two abdominal masses.
      Laboratory analysis of blood showed elevation of the serum level of the CA-125.
      Ultrasonographic examination disclosed bilateral cystic ovarian masses.
      Laparoscopic exploration revealed bilateral ovarian multicystic masses with retro
      uterine peritoneal implant. Bilateral salpingo-oophorectomy with implant
      resection was performed. Histologic findings were consistent with a serous
      borderline tumors of both ovaries and the peritoneal implant was of the non
      invasive type. There is no evidence of recurrence at 3-year follow-up. To our
      knowledge, there are only four cases of ovarian borderline tumors in premenarchal
      girls reported in the English literature: three of the mucinous type and only one
      of the serous type.

PMID- 19837621
TI  - Effects of fusariotoxins in the equine species.
AB  - Fumonisins, trichothecenes and zearalenone are the most commonly occurring
      Fusarium mycotoxins in cereal grains and animal feed. In this review, the
      toxicity of these mycotoxins in horses is considered with particular reference to
      recent data on specific and proposed syndromes. Compared to other animal species,
      very little information is available on the adverse effects of fusariotoxins in
      horses. Fumonisin B(1) (FB(1)) is the causative agent of leukoencephalomalacia,
      which is typified by depression, aimless circling, head pressing, paresis,
      ataxia, blindness and death. FB(1) has also been shown to cause liver damage and
      cardiovascular dysfunction. Exposure to deoxynivalenol in conjunction with other
      fusariotoxins seems to be associated with reduction of feed intake and decrease
      in bodyweight, whilst the T-2 Fusarium mycotoxin may typically induce oral
      lesions and zearalenone has been implicated in reproductive disorders. Many
      questions remain on the synergic effects of fusariotoxins and on a possible
      relationship between mycotoxins and equine colic.

PMID- 19837622
TI  - Protection in the absence of exclusion between two Brazilian isolates of
      Anaplasma marginale in experimentally infected calves.
AB  - This study investigated whether a low pathogenicity isolate of Anaplasma
      marginale with an appendage (UFMG1) could protect calves from infection with a
      pathogenic A. marginale isolate (UFMG2). Two groups of five Friesian calves were
      each inoculated with UFMG1 by intravenous injections of either A. marginale
      infected tick cell cultures (group 1) or blood stabilates (group 2); a third
      (control) group was injected with saline. All animals were inoculated with a
      blood stabilate containing a high pathogenicity A. marginale isolate (UFMG2) 75
      days after the UFMG1 inoculation. After infection with UFMG2, animals in groups 1
      and 2 presented low rickettsaemia, but no clinical signs and no reduction in
      packed cell volume (PCV). Control animals became sick, with high rickettsaemia
      (16% infected erythrocytes) and a reduction in PCV (71%), resulting in 60%
      deaths. Up to 2 weeks after the UFMG2 inoculation, msp1alpha UFMG1 sequences were
      detected in groups 1 and 2. Four weeks after UFMG2 inoculation, UFMG2 sequences
      were detected in these animals, along with a new msp1alpha genotype sequence,
      closely related to that of the UFMG2 isolate. Control animals had UFMG2 msp1alpha
      sequences up to 4weeks after inoculation with UFMG2 and the new msp1alpha
      genotype sequence could be detected on the sixth week. The origin of the new A.
      marginale genotype was unknown, but may represent the first example of MSP1a
      antigenic variation in infected cattle. The results confirmed the low
      pathogenicity of the UFMG1 isolate, which provided clinical protection against
      the highly pathogenic A. marginale UFMG2. Infection with UFMG1 did not prevent
      the establishment of a second isolate, suggesting protection without infection
      exclusion among A. marginale isolates.

PMID- 19837623
TI  - Increased sensitivity to heat pain after sad mood induction in female patients
      with major depression.
AB  - Patients suffering from major depressive disorder (MDD) have been shown to
      exhibit increased thresholds towards experimentally induced thermal pain applied
      to the skin. In contrast, the induction of sad mood can increase pain perception
      in healthy controls. Here, we aimed to test the hypothesis that heat pain
      thresholds are further increased after sad mood induction in depressed patients.
      Thermal pain thresholds were obtained from 25 female depressed patients and 25
      controls before and after sad mood induction applying a modified Velten Mood
      Induction procedure (MIP). Valence and arousal ratings were obtained using the
      self-assessment manikin. The Montgomery Depression Rating Scale and the Beck
      Depression Inventory (BDI) were obtained at baseline from all participants. Pain
      thresholds at baseline did not significantly differ between groups. Pain
      thresholds and valence of mood significantly decreased both in patients and
      controls, while arousal showed an inverse time course between groups. Therefore,
      our hypothesis could not be confirmed. From these data, we propose that the
      depressed mood as seen in MDD patients influences pain experience differently as
      compared to the shorter-lasting mood change after MIP. A differential interaction
      of both affective states with brain areas of the pain matrix might be assumed.
      Eventually, the induction of sad mood might mirror the increased number of pain
      complaints in depressed patients and thus adds to the current concept of adjuvant
      antidepressant treatment both in depressed patients with pain complaints and in
      chronic pain patients.

PMID- 19837624
TI  - [Webliography of health for adolescents and young people].
AB  - AIMS: To identify health Websites in Spanish on adolescence and youth and to
      assess the adequacy of their codes of conduct. METHODS: Cross sectional study of
      the adequacy of codes of conduct, identified in the same way as young people tend
      to look on the Internet (search engines). Websites have been independently
      assessed using a questionnaire by 3 evaluators. Dimensions: 1) accountability, 2)
      transparency and honesty, 3) author, 4) editorial policy, 5) protection of
      personal data, 6) updating of information and accessibility. A descriptive
      analysis was performed and the kappa coefficient was estimated to assess the
      correlation between evaluators. RESULTS: A total of 66.7% of Websites had Spanish
      suppliers. There were 13 Websites (30.9%) with high compliance: Information for
      adolescents from the Spanish Association of Pediatrics (Spain), Health Center
      Manuel Merino Alcala de Henares (Spain), State Family Planning Federation
      (Spain), Webteens of the Generalitat Catalonia (Spain), Young Information
      Institutes Health (USA), Information on Female teenagers (USA), Information
      doctors and educators on type I diabetes (Spain), occupational asthma Portal (10
      countries), teenage Information Puleva Group (Spain), Information bulimia and
      anorexia of the Community of Madrid (Spain), Health of adolescence PulsoMed, SA
      (Spain), American Association of Family Physicians (USA) and Information for
      young people from the Mapfre Health Fund (Spain). The worst dimension was
      updating of information (57.1% with low fullfilment) and protection of personal
      data, 21% with low fullfilment. The level of concordance between observers was
      considerable. CONCLUSIONS: A list was obtained of websites with health
      information on adolescence and youth, with variability in adequacy in codes of
      conduct.

PMID- 19837625
TI  - Place-making, settlement and well-being: the therapeutic landscapes of recently
      arrived youth with refugee backgrounds.
AB  - This paper explores the relationship between place-making, well-being and
      settlement among recently arrived youth with refugee backgrounds in Melbourne,
      Australia. Drawing on qualitative data including photo-novellas and neighborhood
      drawings, we describe the ways youth negotiate connections to place in early
      resettlement. Within the context of broader research on health and place, we
      describe how recently arrived youth actively seek out places with qualities
      associated with restoration and recovery and through these engagements, work to
      create therapeutic landscapes on arrival. The findings have implications for
      understanding the contribution of place-making to well-being in the settlement
      process.

PMID- 19837626
TI  - Does distal tibiofibular joint mobilization decrease limitation of ankle
      dorsiflexion?
AB  - Limitation of ankle motion is in many cases treated by joint mobilization (JM), a
      kind of manual physical therapy technique. Until now, the JM approach has mainly
      focused on the talocrural joint, with less attention to the distal tibiofibular
      joint. We applied cyclic loading to the lateral malleolus as in JM in order to
      clarify the relationship between the dorsiflexion angle and the excursion of the
      lateral malleolus. Seven normal, fresh-frozen cadaver legs were used. To each
      specimen, cyclic loading with a 30N force was applied 1000 times to the lateral
      malleolus at a speed of 15N/s. The displacement of the lateral malleolus was
      measured with a magnetic tracking system. The maximum dorsiflexion angle was
      measured before and after cyclic loading. After the first 100 and 1000 times of
      cyclic loading, the tibia was displaced 0.44+/-0.30mm and 0.75+/-0.36mm,
      respectively, and the fibula was displaced 0.44+/-0.28mm and 0.92+/-0.39mm,
      respectively. The average dorsiflexion angle increased from 14.36+/-7.51 degrees
      to 16.74+/-7.21 degrees after cyclic loading (P<0.05). Movement of the distal
      tibiofibular joint led to a significant increase in the range of ankle
      dorsiflexion. These results suggest that tibiofibular JM would be effective for
      limitation of ankle dorsiflexion.

PMID- 19837627
TI  - Integrated omics approaches in plant systems biology.
AB  - Understanding cellular metabolic systems is vital not only for determining the
      function of enzymatic genes, but also for elucidating the coordination among
      various metabolic pathways. In this context, high-throughput experiments can
      provide us with essential, albeit only partial information. Integration of
      metabolite profiling with other multiple 'omics' data (e.g. transcript
      profiling), is required to reconstruct complex networks that characterize the
      phenotypes in the cell. Here, we review recent approaches to integrate multiple
      omics data in higher plants. We especially focus on metabolomics data management,
      normalization, meta-omics data analysis, and an integrative approach with other
      omics data. Further prospects for using metabolomics and the key points to be
      addressed are discussed. This could be a valuable strategy for a systems-level
      understanding of plant systems.

PMID- 19837628
TI  - CDKs and the yeast-hyphal decision.
AB  - Fungal cells exist in a diverse range of morphologies. Some species, such as
      Candida albicans, are dimorphic capable of growing either in a yeast-like form or
      as a hypha. Cyclin-dependent kinases (CDKs) have long been thought to play a
      central role in the yeast-hyphal decision. However, until recently direct links
      of CDKs with proteins that execute polarized growth were elusive. In this review
      I will focus on new findings that have established concrete links between CDKs
      and several key components of the polarity machinery in C. albicans and the
      budding yeast Saccharomyces cerevisiae. Inhibitory phosphorylation of the GTPase
      activating proteins (GAPs) of Cdc42 has emerged as a common mechanism underlying
      polarized growth in both organisms. C. albicans contains a hyphal-specific cyclin
      Hgc1. In association with the CDK Cdc28 it ensures hyphal development by
      phosphorylating the Cdc42 GAP Rga2, two septins and the transcription factor
      Efg1. This review will discuss both conserved mechanisms and ones specific for
      hyphal development in C. albicans.

PMID- 19837629
TI  - Classification of patterns of EEG synchronization for seizure prediction.
AB  - OBJECTIVE: Research in seizure prediction from intracranial EEG has highlighted
      the usefulness of bivariate measures of brainwave synchronization. Spatio
      temporal bivariate features are very high-dimensional and cannot be analyzed with
      conventional statistical methods. Hence, we propose state-of-the-art machine
      learning methods that handle high-dimensional inputs. METHODS: We computed
      bivariate features of EEG synchronization (cross-correlation, nonlinear
      interdependence, dynamical entrainment or wavelet synchrony) on the 21-patient
      Freiburg dataset. Features from all channel pairs and frequencies were aggregated
      over consecutive time points, to form patterns. Patient-specific machine learning
      based classifiers (support vector machines, logistic regression or convolutional
      neural networks) were trained to discriminate interictal from preictal patterns
      of features. In this explorative study, we evaluated out-of-sample seizure
      prediction performance, and compared each combination of feature type and
      classifier. RESULTS: Among the evaluated methods, convolutional networks combined
      with wavelet coherence successfully predicted all out-of-sample seizures, without
      false alarms, on 15 patients, yielding 71% sensitivity and 0 false positives.
      CONCLUSIONS: Our best machine learning technique applied to spatio-temporal
      patterns of EEG synchronization outperformed previous seizure prediction methods
      on the Freiburg dataset. SIGNIFICANCE: By learning spatio-temporal dynamics of
      EEG synchronization, pattern recognition could capture patient-specific seizure
      precursors. Further investigation on additional datasets should include the
      seizure prediction horizon.

PMID- 19837630
TI  - Comparison of segmental linear and angular momentum transfers in two-handed
      backhand stroke stances for different skill level tennis players.
AB  - The purpose of this study was to investigate the differences of momentum transfer
      from the trunk and upper extremities to the racket between open and square
      stances for different skill levels players in the two-handed backhand stroke. The
      motion capture system with twenty-one reflective markers attached on anatomic
      landmarks of the subject was used for two-handed backhand stroke motion data
      collection. Twelve subjects were divided into an advanced group and an
      intermediate group based on skill level. The three-dimensional linear and angular
      momentums of the trunk, upper arm, forearm, hand and racket were used for kinetic
      chain analysis. Results showed that all players with the square stance had
      significantly larger backward linear momentum contribution in trunk and upper arm
      than with the open stance (p<.05) irrespective of playing level. However, the
      external rotation angular momentum of the shoulder joint was significantly larger
      with an open stance than with a square stance (p=.047). Comparison of playing
      levels showed that the intermediate group performed higher linear momentum in
      three components of the trunk, upper arm backward linear momentum, and trunk
      right bending angular momentum than the advanced group significantly (p<.05). The
      advanced group reduces trunk linear movement to keep stability and applies trunk
      and linkage segment rotation to generate backhand stroke power. The advanced
      group also has a quick backswing for increasing acceleration and maintains longer
      in the follow-through phase for shock energy absorption. This information could
      improve training protocol design for teaching the two-handed backhand stroke and
      teaching players, especially beginners, how to make an effective stroke.

PMID- 19837631
TI  - Dimerization of dopamine D1 and D3 receptors in the regulation of striatal
      function.
AB  - Co-localization of dopamine D1 (D1R) and D3 receptors (D3R) in specific neuronal
      populations in the striatum and nucleus accumbens suggests that their cross-talk
      in the regulation of rewarding mechanisms and emotional and cognitive processes
      and in the development of motor dysfunctions might involve direct interactions.
      This paper summarizes recent data showing that D1R and D3R form a receptor
      heteromer in the striatum. A unique characteristic of this receptor complex is a
      synergistic interaction by which D3R stimulation increases D1R agonist affinity,
      allows a stronger stimulatory coupling of the D1R to the cAMP system and
      potentiates D1R-mediated behaviour. The putative role of the D1R-D3R heteromer in
      the development of motor dysfunctions is also discussed.

PMID- 19837632
TI  - Lymph node tumor metastases: more susceptible than primary tumors to CD8(+) T
      cell immune destruction.
AB  - Hematopoietic cells, and more particularly, dendritic cells are so called
      "professional" antigen-presenting cells, which prime CD8(+) T-cell responses.
      They achieve this by taking up antigens and presenting them to CD8(+) T cells in
      the draining lymph nodes. This process is called cross-presentation (XP). For
      most developing tumors, XP of tumor antigens results in CD8(+) T-cell tolerance.
      In addition to XP, direct presentation by any kind of cell can also occur in
      lymph nodes. We discuss here how a non-hematopoietic cell can efficiently prime
      CD8(+) T cells by direct presentation in lymph nodes. Such a T-cell activation
      pathway is likely to be of importance for the control of cancer metastases that
      use the lymphatic system to spread.

PMID- 19837633
TI  - Malaria vaccines - how and when to proceed?
AB  - In the field of malaria vaccines, there are many barriers to moving lead
      candidates from the bench into developmental programmes before clinical testing.
      Many of the same challenges are to be found in the field of vaccines for other
      infectious diseases. Here, we briefly outline the process of pre-clinical
      development to help identify ways to support the translation of laboratory-based
      information into viable vaccine candidates.

PMID- 19837634
TI  - Assessment of urethral plate appearance through digital photography: do pediatric
      urologists agree in their visual impressions of the urethral plate in children
      with hypospadias?
AB  - OBJECTIVE: There is a paucity of literature on a definition or set criteria
      evaluating urethral plate (UP) quality. We sought to determine whether pediatric
      urologists are in agreement in their assessment of UP quality. MATERIALS AND
      METHODS: A cohort of 21 pediatric urologists attending a national annual meeting
      were surveyed with a questionnaire inquiring about practice patterns and
      perceived impressions of UP quality. Nineteen sequentially projected,
      standardized, digital photographs, depicting plates with variable meatal
      locations, were presented. Intra- and inter-rater agreement among pediatric
      urologists was estimated by calculating the Kappa statistic (kappa). RESULTS:
      Thirty percent of respondents had more than 15years of practice and one-third
      repair 10 or more hypospadias per month. Measurement of level of agreement in the
      impression of UP quality of the 18 projected photographs revealed poor inter
      rater agreement (kappa=0.06, P=0.0003), which was not improved by focusing on
      particular meatal locations or surgeon experience. CONCLUSIONS: Despite the
      inherent shortcomings of digital photography, this study highlights the potential
      subjectivity and lack of agreement on UP quality. Disagreement seems to be
      present irrespective of level of the defect or surgeon experience. Setting
      standards and improving agreement is likely to enhance reporting and
      interpretation of data in hypospadias studies.

PMID- 19837635
TI  - Immunoexpression of adrenergic receptors in detrusor from patients with prune
      belly syndrome: a digital quantification.
AB  - INTRODUCTION: Prune belly syndrome (PBS) presents with large-capacity bladders,
      high compliance and post-void residual volumes. Operative and conservative
      treatments are controversial. When histologically compared to normal bladder,
      bladder outlet obstruction results in an up- or down-regulation of adrenoceptors.
      Our goal was to study the immunoexpression of adrenoceptors in detrusor from
      patients with PBS. MATERIALS AND METHODS: Bladder domes from PBS patients (n=14)
      were studied (PBG). For normal controls, bladder specimens were obtained at adult
      surgery (n=13) (CG1) and at child autopsy (n=5) (CG2). Staining was performed
      using antibodies to alpha1a, alpha1b, alpha1d and beta3 adrenoceptors. Five to 10
      images were captured on an optic microscope with a digital camera and analysed
      with Photoshop. The immunocyhistochemical index with arbitrary units was
      calculated and compared. RESULTS: Mean age was 1.28, 64 and 1.41 years for PBG,
      CG1 and CG2, respectively. The immunohistochemical index with arbitrary units of
      alpha1a receptors was 0.06 in PBG, 0.16 in CG1 and 0.14 in CG2 (p=0.008); of
      alpha1b 0.06, 0.06 and 0.07 (p=0.781); and of alpha1d 0.04, 0.04 and 0.05
      (p=0.618). Regarding beta3 the respective values were 0.07, 0.14 and 0.10
      (p=0.378). CONCLUSION: Our results show a decrease in alpha1a-adrenoceptor
      immunostaining intensity in detrusor from children with PBS. Further in vitro
      studies are needed to determine whether these observations are physiologically
      significant.

PMID- 19837636
TI  - Simultaneous extraction and screening of diuretics, beta-blockers, selected
      stimulants and steroids in human urine by HPLC-MS/MS and UPLC-MS/MS.
AB  - Described herein are two general screening procedures for the simultaneous
      determination of 49 exogenous compounds (21 diuretics, 19 beta-blockers, eight
      stimulants and two steroidal drugs) in human urine by high performance liquid
      chromatography tandem mass spectrometry (HPLC-MS/MS) and ultra performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS). Urine samples were
      extracted using a simple and robust solid phase extraction (SPE) method. Samples
      were injected onto reversed phase HPLC and UPLC columns connected to tandem mass
      spectrometers capable of scan-to-scan polarity switching. The methods were
      validated according to the ISO 17025 international standard for the validation of
      a qualitative method. Sixty urine samples submitted for routine analysis were
      tested using both methods, the results of which correlated with results obtained
      from previously validated procedures. Both methods proved to be useful for
      routine urine analysis; most notably, the use of UPLC-MS/MS demonstrated that
      samples can be reliably screened with significantly reduced analysis times.

PMID- 19837637
TI  - [Desmoplastic fibroma of the jaw: a rare kind of tumour].

PMID- 19837638
TI  - Predicting excessive body image concerns among British university students: the
      unique role of Appearance-based Rejection Sensitivity.
AB  - The present research examined the extent to which interpersonal concerns about
      rejection based on appearance, or Appearance-based Rejection Sensitivity
      (Appearance-RS), serves as an indicator of risk for excessive body image
      concerns. Extending previous research, we examined the association between
      Appearance-RS and symptoms of body dysmorphic disorder (BDD) and cosmetic surgery
      attitudes among 106 British university students. Consistent with predictions,
      Appearance-RS uniquely predicted greater degree of BDD symptoms after controlling
      for other known predictor variables. Also, as expected, Appearance-RS uniquely
      predicted acceptance of cosmetic surgery for both intrapersonal and social
      reasons and greater consideration of having cosmetic surgery in the future. These
      findings highlight the importance of assessing individuals' sensitivity to
      rejection from others based on their physical appearance in investigations of
      excessive body image concerns.

PMID- 19837639
TI  - A preliminary investigation of the relationship between induced rumination and
      state body image dissatisfaction and anxiety.
AB  - The current study investigated the relationship between cognitive rumination and
      state body image distress using an experimental design. Specifically, the study
      examined whether participants induced to ruminate about an imagined negative body
      image event would report more body image dissatisfaction and anxiety compared to
      those induced to distract themselves. Ninety-nine undergraduate women completed
      two measures to assess depressive symptomology and baseline body image distress.
      All participants then silently read a body image scenario intended to evoke
      negative emotions. After reading the scenario, participants were randomized into
      one of two conditions, rumination or distraction, and were then re-administered
      the self-report measures. Statistical analyses revealed that the rumination group
      reported more state body image dissatisfaction and anxiety after the
      manipulation. The findings provide preliminary support for the hypothesis that a
      ruminative response style, specifically within a body image domain, predicts body
      image dissatisfaction and anxiety.

PMID- 19837640
TI  - Diabetes care in Ireland: a survey of general practitioners.
AB  - AIM: To investigate the organisation of diabetes care in general practice in
      Ireland and identify areas for future development. METHODS: Survey of a
      representative sample of 600 general practitioners (GPs). The questionnaire
      contained closed and open-ended questions addressing 4 topics; characteristics of
      the practice, diabetes care delivery, use of services and opportunities for
      developing diabetes care. RESULTS: The response rate was 44% (n=262). There were
      an additional 86 responses to a follow-up shortened version of the survey
      resulting in a 58% response rate for 9 key questions. The majority of respondents
      were from an urban (43%, n=112) or a mixed area (39%, n=101) and 19% of practices
      were single-handed (n=66). The reported prevalence in participating practices was
      0.7% for Type 1 diabetes and 2.8% for Type 2 diabetes. Forty-five percent of GPs
      maintained a diabetes register (n=157) while 53% reported using guidelines
      (n=140). A formal call recall system was reported by 30% (n=78) with a further
      20% (n=54) reporting a regular if informal approach to calling patients for
      review. With regard to the use of diabetes related services 63% reported direct
      access to a dietician (n=165), 57% direct access to chiropody services (n=149)
      and 89% had direct access to retinopathy screening (n=234). There was a
      significant association between maintaining a diabetes register and other aspects
      of care delivery such as engaging in formal recall (p<0.001), using guidelines
      (p<0.001) and a declared special interest in diabetes (p=0.001). Of a number of
      choices 75% of GPs thought that training was the principal opportunity for
      improving diabetes care. In response to the open-ended questions GPs cited lack
      of resources, time constraints and workload as barriers to effective care
      delivery. CONCLUSIONS: Delivery of diabetes care in Ireland remains largely
      unstructured. Key challenges to improving diabetes care appear to extend to the
      system and organisational level of care delivery.

PMID- 19837641
TI  - Modeling the evolution of culture-adapted human embryonic stem cells.
AB  - The long-term culture of human embryonic stem (ES) cells is inevitably subject to
      evolution, since any mutant that arises with a growth advantage will be
      selectively amplified. However, the evolutionary influences of population size,
      mutation rate, and selection pressure are frequently overlooked. We have
      constructed a Monte Carlo simulation model to predict how changes in these
      factors can influence the appearance and spread of mutant ES cells, and verified
      its applicability by comparison with in vitro data. This simulation provides an
      estimate for the expected rate of generation of culture-adapted ES cells under
      different assumptions for the key parameters. In particular, it highlights the
      effect of population size, suggesting that the maintenance of cells in small
      populations reduces the likelihood that abnormal cultures will develop.

PMID- 19837642
TI  - Complications following rotating hinge Endo-Modell (Link) knee arthroplasty.
AB  - BACKGROUND: Rotating hinge knee prostheses are indicated in revisions especially
      when major ligament laxity or substantial AP deformities are present. These
      situations make ligament balancing difficult with less constrained design
      implants. Despite its use for nearly 50 years, this type of prosthesis continues
      to have a poor reputation due to a high complication rate. HYPOTHESIS:
      Complications are frequent after this type of arthroplasty and the complication
      rate is similar in primary or revision arthroplasties. The objective of this
      study is to report the medium-term results of these implants and determine the
      eventual predictive factors of complications in order to refine operative
      indications. MATERIAL AND METHODS: In this retrospective study of patients
      operated on between 1998 and 2006, 85 Endo-Modell (Link) rotating hinge knee
      prostheses had been used in 61 females and 24 males. The mean age at surgery was
      72.4 years (range, 32-92 years). Fifty-two arthroplasties were primary and 33
      were revisions either for loosening (24) or deep infections (9). The mean follow
      up was 36 months+/-22 (range, 0-75 months). RESULTS: Complications were observed
      in 24 patients (28.2%): nine deep infections, four patellar complications, and
      three cases of aseptic loosening. No significant difference was found between the
      primary arthroplasties and the revisions regarding all complication types. A
      significant relation was established between the occurrence of a complication and
      presence of several associated comorbidity factors (obesity, heart disease,
      diabetes, etc.). DISCUSSION: The use of this type of implant carries a high risk
      of complications, higher than the one pertaining to unconstrained design
      prostheses; this fact is noted irrespective of the surgical indication and other
      comparison elements. The leading criteria to poor functional results appear to be
      the indication (gonarthrosis with substantial ligament laxity at primary surgery)
      and the number of associated comorbidities. These prostheses should therefore be
      restricted to selected indications, notably in view of the fact that less
      constrained prostheses give superior outcomes. LEVEL OF EVIDENCE: Level IV.
      Retrospective therapeutic study.

PMID- 19837643
TI  - Social engagement in the elderly.

PMID- 19837644
TI  - Dexamethasone inhibits tumor necrosis factor-alpha-stimulated gastric epithelial
      cell migration.
AB  - BACKGROUND: Cell migration (restitution) occurs in the early phase of gastric
      ulcer healing. Tumor necrosis factor (TNF)-alpha is overexpressed at the ulcer
      margin and plays a physiologic role in gastric ulcer healing. Dexamethasone,
      which is a potent corticosteroid, delays rat gastric ulcer healing. We evaluated
      whether dexamethasone inhibited TNF-alpha-stimulated gastric epithelial cell
      migration using a rat normal gastric epithelial cell line (RGM-1). METHODS: An
      artificial wound model was employed to measure cell migration. Western blot was
      performed to evaluate the possible mechanisms. Intracellular prostaglandin E2
      level was measured using an enzyme-linked immunosorbent assay. RESULTS: TNF-alpha
      treatment (10 ng/mL) for 12-48 hours significantly increased RGM-1 cell
      migration, and TNF-alpha treatment increased cyclooxygenase (COX)-2 protein
      expression 8 hours later and prostaglandin E2 (PGE2) synthesis 12 hours later
      compared with control (p < 0.05). Dexamethasone (10(-6) M) significantly
      inhibited the stimulatory effect of TNF-alpha on RGM-1 cell migration, which was
      associated with a significant decrease in COX-2 expression and PGE2 level in
      cells (p < 0.05). CONCLUSION: TNF-alpha plays a regulatory role in rat gastric
      epithelial cell migration and dexamethasone inhibited TNF-alpha-stimulated cell
      migration, which was associated with a decrease in COX-2 expression and PGE2
      formation.

PMID- 19837645
TI  - Sectional anatomy of the optic pathways on the coronal plane.
AB  - BACKGROUND: The purpose of this study was to provide practical data for the
      imaging diagnosis of the optic pathways. METHODS: Sectional anatomy of the optic
      pathways on the coronal plane was investigated on 15 sets of serial coronal
      sections of the head of Chinese adult cadavers and 6 sets of serial coronal
      magnetic resonance imaging of normal adults. RESULTS: On the coronal plane, we
      recognized the special structures of optic pathways by 5 key sections. (1) The
      midorbital optic nerve lay superomedially in the center of the adipose body of
      the orbit, surrounded by the subarachnoid space and the sheath of the optic
      nerve. (2) The optic chiasma was transverse between the optic and infundibular
      recesses of the portion of the floor of the third ventricle and it lay below the
      A1 segment of the anterior cerebral artery and above the tuber cinereum and the
      pituitary stalk, C2 or C3 segment of the internal carotid artery laterally. (3)
      The optic tract lay between the crus cerebri and the amygdaloid, the tail of the
      caudate nucleus laterally. The anterior choroidal artery inferiorly and downward
      M2 segment of the middle cerebral artery lay between the uncus and the crus
      cerebri. (4) The lateral geniculate body lay between the crus cerebri medially
      and the tail of the caudate nucleus laterally, the uncus and P2 segment of the
      posterior cerebral artery inferiorly. (5) The optic radiation formed the lateral
      wall of the lateral ventricle both in the temporal horn and in the occipital
      horn. The optic radiation was separated from the wall of the occipital horn by
      the tapetum, a thin layer of fibers derived from the splenium of the corpus
      callosum. Coronal sectional anatomy and magnetic resonance imaging of the optic
      pathways revealed similar results. CONCLUSION: This study provides a good
      understanding of the structures of the optic pathways by correlation of coronal
      sections of the head of adult cadavers with the coronal magnetic resonance images
      of normal adults.

PMID- 19837646
TI  - A model for predicting risk of serious bacterial infection in febrile infants
      younger than 3 months of age.
AB  - BACKGROUND: The objective of this study was to construct a model for predicting
      the risk of serious bacterial infection (SBI) in febrile infants. METHODS: A
      total of 135 febrile infants younger than 3 months of age who met the inclusion
      criteria were assessed on the following: physical appearance, complete blood
      count, serum C-reactive protein (CRP), urinalysis, stool smears for white blood
      cell (WBC) count if diarrhea was apparent, and blood and urine cultures. Chest X
      rays were performed if respiratory symptoms were evident. Cerebrospinal fluid was
      analyzed if central nervous system infection was suspected. RESULTS: Of the 135
      infants, 34 were diagnosed with SBI. Data from 99 infants were used to construct
      a model for predicting SBI by multivariate logistic regression. Sex (male), spun
      urine WBC count (>or= 10 per high-powered field [400x]) and CRP (>or= 3.6 mg/L)
      were significantly related to SBI. A probability cut-off of 0.265 was selected,
      where values below and above the cut-off reflected low and high SBI risk
      respectively. Data from the remaining 36 infants were used to test model
      validity. Both sensitivity and specificity were 77.8% for predicting SBI using
      this model. CONCLUSION: These findings suggest that sex, serum CRP concentration
      and spun urine WBC count can be used to accurately predict SBI in febrile infants
      aged less than 3 months of age.

PMID- 19837647
TI  - High-resolution computed tomography in the diagnosis of otosclerosis in Taiwan.
AB  - BACKGROUND: Otosclerosis is rare in Asians, and the clinical role of imaging
      remains controversial. We sought to clarify the tomographic findings of
      otosclerosis in Taiwanese patients and determine the value and necessity of high
      resolution computed tomography (HRCT) of the temporal bone in diagnosing the
      disease in Taiwan. METHODS: This retrospective study enrolled 22 patients (24
      ears) with clinically, surgically and pathologically confirmed otosclerosis. All
      subjects underwent HRCT of the temporal bone; the images were then reviewed at
      workstations. The control group consisted of 15 patients. RESULTS: HRCT was
      positive in 46% of the clinically, surgically and pathologically confirmed
      otosclerotic ears. Patients with a positive imaging study had a smaller
      preoperative air-bone gap and a significantly shorter duration of the disease.
      The duration of the disease also tended to be greater in patients with a larger
      preoperative air-bone gap. CONCLUSION: HRCT has high specificity (100%) but low
      sensitivity (46%) for the diagnosis of otosclerosis in Taiwanese patients despite
      progress in radiology. The low image positive rate we found, compared with that
      in Western literature, may stem from a greater percentage of inactive
      otosclerosis.

PMID- 19837648
TI  - Homologous type of malignant mixed Mullerian tumor of the uterus presenting as a
      cervical mass.
AB  - Malignant mixed Mullerian tumors are composed of a mixture of sarcoma and
      carcinoma. The carcinomatous element is usually glandular, whereas the
      sarcomatous element may resemble normal endometrial stroma (homologous or so
      called carcinosarcoma). Here, we present a homologous type of malignant mixed
      Mullerian tumor of the uterus that presented as a cervical mass. We describe a 55
      year-old patient who had a cervical mass arising from the uterus. We performed
      total abdominal hysterectomy and bilateral salpingo-oophorectomy and surgical
      staging (including (peritoneal washings, suspicious areas or peritoneal surfaces
      sampled, infracolic omental sampling, pelvic and paraaortic lymph node sampling,
      and appendectomy). Carcinosarcomas of the uterine cervix are extremely rare, and
      when a postmenopausal woman with a cervical mass is admitted to the gynecology
      clinic, the physician should keep in mind that the mass might be a
      carcinosarcoma.

PMID- 19837649
TI  - Primary intradural hemangiopericytoma with intramedullary invasion.
AB  - Hemangiopericytoma (HPC) is a rare tumor of the central nervous system and is
      usually found intracranially. Intraspinal HPCs are very rare and mostly involve
      the extradural bony structures. Primary intradural HPC has only been reported in
      10 cases, all of which occurred in the extramedullary region. Intramedullary
      invasion has never been reported. Here, we describe a case of primary intradural
      HPC of the thoracic spine that presented initially with paresthesia and
      paraplegia of both legs. Magnetic resonance imaging of the thoracic spine showed
      an intradural dumbbell-shaped tumor at the T10 level. The initial impression was
      neurogenic tumor, meningioma, or metastasis. During operation, the tumor was
      found to have obvious intramedullary invasion. Gross-total removal was done, and
      the patient's neurological function improved; there was no recurrence at the 3
      year follow-up. There is no consensus as to what constitutes the optimal
      treatment of HPC, but most neurosurgeons will advocate gross-total resection. A
      comparative analysis between intradural and extradural HPCs showed a higher
      chance of gross-total resection for intradural HPCs, while the recurrence rates
      showed no difference. The role of adjuvant radiotherapy remains uncertain. Due to
      the high risk of recurrence and metastasis of HPCs, close follow-up for a long
      period is mandatory.

PMID- 19837650
TI  - Extramammary Paget's disease of the scrotum associated with hepatocellular
      carcinoma.
AB  - Extramammary Paget's disease (EMPD) is a rare cutaneous carcinoma of epidermal
      origin. The diagnosis is frequently delayed, and the disease tends to be
      associated with an underlying adnexal or internal malignancy. There have been
      several reports of EMPD associated with carcinoma of the bladder, prostate,
      kidney, and colon. The association of hepatocellular carcinoma (HCC) with EMPD
      appears to be exceedingly rare; to our knowledge, it has been reported only once
      in the English literature. Herein, we report an unusual case of EMPD of the
      scrotum associated with HCC. EMPD was diagnosed 1 year after the appearance of an
      erythematous plaque, and HCC was noted 19 months after the diagnosis of EMPD.
      From our experience and literature review, in patients with nonspecific skin
      lesions that are unresponsive to conventional treatment, EMPD should be
      considered and skin biopsy performed. Long-term follow-up is needed to watch for
      the appearance of adnexal carcinoma or internal malignancy.

PMID- 19837651
TI  - Intravenous paraquat poisoning.
AB  - Paraquat is a substance that is highly poisonous to humans. Oral ingestion is the
      most common pathway of poisoning. Intravenous paraquat poisoning is rare and is
      strongly associated with attempted suicide. The clinical presentations of such a
      scenario would appear to be quite different from those of oral ingestion. Herein,
      we present a case of an intravenous drug abuser who injected paraquat in an
      effort to commit suicide. He received hemoperfusion and intravenous
      cyclophosphamide treatment and parenteral pulse therapy with methylprednisolone.
      Nevertheless, he suffered from dyspnea at around 48 hours post-exposure. His
      condition improved transiently, but he eventually died from severe hypoxia. The
      findings from our case and those of previously reported cases indicate the grave
      prognosis and lack of effective management of intravenous paraquat poisoning.

PMID- 19837652
TI  - Aorto-left renal cyst fistula: a rare complication of abdominal aortic aneurysm
      rupture.
AB  - Abdominal aortic aneurysm (AAA) rupture can occur in different ways, such as
      closed rupture into the retroperitoneum, open rupture into the peritoneal cavity,
      rupture into surrounding hollow structures, and chronic contained or sealed
      rupture. Here, we report an unusual case of spontaneous rupture of AAA into a
      renal cyst that presented with hematuria, abdominal pain and shock, and which was
      diagnosed with multidetector computed tomography. We also review the literature
      on unusual patterns of AAA rupture.

PMID- 19837653
TI  - Extreme hypernatremia combined with rhabdomyolysis and acute renal failure.
AB  - Rhabdomyolysis is a life-threatening condition that involves muscle cell
      destruction. Among its etiologies, severe hypernatremia is a less common cause.
      We report a teenage girl with congenital central hypoventilation syndrome and
      hypothalamus dysfunction syndrome who presented with extreme hypernatremia
      (sodium, 211 mmol/L) with rhabdomyolysis (creatine kinase, 32,850 U/L) and acute
      renal failure (creatinine, 6.1 mg/dL) following gastroenteritis with 7-kg weight
      loss. Rhabdomyolysis subsequently led to acute renal failure and hyperkalemia.
      Acute hemodialysis was initiated on hospital day 3 for hyperkalemia. This
      resulted in a 13 mmol/L fall in serum sodium in 3 hours despite using a 156
      mmol/L sodium bath, but without the development of cerebral edema or neurological
      defect. This report highlights an unusual cause of rhabdomyolysis in children and
      the experience of managing such a difficult clinical situation.

PMID- 19837654
TI  - PICNIC: an algorithm to predict absolute allelic copy number variation with
      microarray cancer data.
AB  - High-throughput oligonucleotide microarrays are commonly employed to investigate
      genetic disease, including cancer. The algorithms employed to extract genotypes
      and copy number variation function optimally for diploid genomes usually
      associated with inherited disease. However, cancer genomes are aneuploid in
      nature leading to systematic errors when using these techniques. We introduce a
      preprocessing transformation and hidden Markov model algorithm bespoke to cancer.
      This produces genotype classification, specification of regions of loss of
      heterozygosity, and absolute allelic copy number segmentation. Accurate
      prediction is demonstrated with a combination of independent experimental
      techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data
      from 755 cancer cell lines, enabling inference upon a number of features of
      biological interest. These data and the coded algorithm are freely available for
      download.

PMID- 19837655
TI  - Varying-coefficient models for longitudinal processes with continuous-time
      informative dropout.
AB  - Dropout is a common occurrence in longitudinal studies. Building upon the pattern
      mixture modeling approach within the Bayesian paradigm, we propose a general
      framework of varying-coefficient models for longitudinal data with informative
      dropout, where measurement times can be irregular and dropout can occur at any
      point in continuous time (not just at observation times) together with
      administrative censoring. Specifically, we assume that the longitudinal outcome
      process depends on the dropout process through its model parameters. The
      unconditional distribution of the repeated measures is a mixture over the dropout
      (administrative censoring) time distribution, and the continuous dropout time
      distribution with administrative censoring is left completely unspecified. We use
      Markov chain Monte Carlo to sample from the posterior distribution of the
      repeated measures given the dropout (administrative censoring) times; Bayesian
      bootstrapping on the observed dropout (administrative censoring) times is carried
      out to obtain marginal covariate effects. We illustrate the proposed framework
      using data from a longitudinal study of depression in HIV-infected women; the
      strategy for sensitivity analysis on unverifiable assumption is also
      demonstrated.

PMID- 19837656
TI  - Novel venom proteins produced by differential domain-expression strategies in
      beaded lizards and gila monsters (genus Heloderma).
AB  - The origin and evolution of venom proteins in helodermatid lizards were
      investigated by multidisciplinary techniques. Our analyses elucidated novel toxin
      types resultant from three unique domain-expression processes: 1) The first full
      length sequences of lethal toxin isoforms (helofensins) revealed this toxin type
      to be constructed by an ancestral monodomain, monoproduct gene (beta-defensin)
      that underwent three tandem domain duplications to encode a tetradomain,
      monoproduct with a possible novel protein fold; 2) an ancestral monodomain gene
      (encoding a natriuretic peptide) was medially extended to become a pentadomain,
      pentaproduct through the additional encoding of four tandemly repeated proline
      rich peptides (helokinestatins), with the five discrete peptides liberated from
      each other by posttranslational proteolysis; and 3) an ancestral multidomain,
      multiproduct gene belonging to the vasoactive intestinal peptide (VIP)/glucagon
      family being mutated to encode for a monodomain, monoproduct (exendins) followed
      by duplication and diversification into two variant classes (exendins 1 and 2 and
      exendins 3 and 4). Bioactivity characterization of exendin and helokinestatin
      elucidated variable cardioactivity between isoforms within each class. These
      results highlight the importance of utilizing evolutionary-based search
      strategies for biodiscovery and the virtually unexplored potential of lizard
      venoms in drug design and discovery.

PMID- 19837657
TI  - Natural selection on synonymous and nonsynonymous mutations shapes patterns of
      polymorphism in Populus tremula.
AB  - One important goal of population genetics is to understand the relative
      importance of different evolutionary processes for shaping variation in natural
      populations. Here, I use multilocus data to show that natural selection on both
      synonymous and nonsynonymous mutations plays an important role in shaping levels
      of synonymous polymorphism in European aspen (Populus tremula). Previous studies
      have documented a preferential fixation of synonymous mutations encoding
      preferred codons in P. tremula. The results presented here show that this has
      resulted in an increase in codon bias in P. tremula, consistent with stronger
      selection acting on synonymous codon usage. In addition, positive selection on
      nonsynonymous mutations appears to be common in P. tremula, with approximately
      30% of all mutations having been fixed by positive selection. In addition, the
      recurrent fixation of beneficial mutations also reduces standing levels of
      polymorphism as evidenced by a significantly negative relationship between the
      rate of protein evolution synonymous site diversity and silent site diversity.
      Finally, I use approximate Bayesian methods to estimate the strength of selection
      acting on beneficial substitutions. These calculations show that recurrent
      hitchhiking reduces polymorphism by, on average, 30%. The product of strength of
      selection acting on beneficial mutations and the rate by which these occur across
      the genome (2N(e)lambdas) equals 1.54x10( - 7), which is in line with estimates
      from Drosophila where recurrent hitchhiking has also been shown to have
      significant effects on standing levels of polymorphism.

PMID- 19837658
TI  - Substrate-induced assembly of Methanococcoides burtonii D-ribulose-1,5
      bisphosphate carboxylase/oxygenase dimers into decamers.
AB  - Like many enzymes, the biogenesis of the multi-subunit CO(2)-fixing enzyme
      ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) in different
      organisms requires molecular chaperones. When expressed in Escherichia coli, the
      large (L) subunits of the Rubisco from the archaeabacterium Methanococcoides
      burtonii assemble into functional dimers (L(2)). However, further assembly into
      pentamers of L(2) (L(10)) occurs when expressed in tobacco chloroplasts or E.
      coli producing RuBP. In vitro analyses indicate that the sequential assembly of
      L(2) into L(10) (via detectable L(4) and L(6) intermediates) occurs without
      chaperone involvement and is stimulated by protein rearrangements associated with
      either the binding of substrate RuBP, the tight binding transition state analog
      carboxyarabinitol-1,5-bisphosphate, or inhibitory divalent metal ions within the
      active site. The catalytic properties of L(2) and L(10) M. burtonii Rubisco (MbR)
      were indistinguishable. At 25 degrees C they both shared a low specificity for
      CO(2) over O(2) (1.1 mol x mol(-1)) and RuBP carboxylation rates that were
      distinctively enhanced at low pH (approximately 4 s(-1) at pH 6, relative to 0.8
      s(-1) at pH 8) with a temperature optimum of 55 degrees C. Like other archaeal
      Rubiscos, MbR also has a high O(2) affinity (K(m)(O(2)) = approximately 2.5
      microM). The catalytic and structural similarities of MbR to other archaeal
      Rubiscos contrast with its closer sequence homology to bacterial L(2) Rubisco,
      complicating its classification within the Rubisco superfamily.

PMID- 19837659
TI  - Alphav beta3 integrin limits the contribution of neuropilin-1 to vascular
      endothelial growth factor-induced angiogenesis.
AB  - Both vascular endothelial growth factor receptors (VEGFR) and integrins are major
      regulators of VEGF-induced angiogenesis. Previous work has shown that beta3
      integrin can regulate negatively VEGFR2 expression. Here we show that beta3
      integrin can regulate negatively VEGF-mediated angiogenesis by limiting the
      interaction of the co-receptor NRP1 (neuropilin-1) with VEGFR2. In the presence
      of alphav beta3 integrin, NRP1 contributed minimally to VEGF-induced angiogenic
      processes in vivo, ex vivo, and in vitro. Conversely, when beta3 integrin
      expression is absent or low or its function is blocked with RGD-mimetic
      inhibitors, VEGF-mediated responses became NRP1-dependent. Indeed, combined
      inhibition of beta3 integrin and NRP1 decreased VEGF-mediated angiogenic
      responses further than individual inhibition of these receptors. We also show
      that alphav beta3 integrin can associate with NRP1 in a VEGF-dependent fashion.
      Our data suggest that beta3 integrin may, in part, negatively regulate VEGF
      signaling by sequestering NRP1 and preventing it from interacting with VEGFR2.

PMID- 19837660
TI  - Direct sensing of intracellular pH by the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl- channel.
AB  - In cystic fibrosis (CF), dysfunction of the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl(-) channel disrupts epithelial ion transport and
      perturbs the regulation of intracellular pH (pH(i)). CFTR modulates pH(i) through
      its role as an ion channel and by regulating transport proteins. However, it is
      unknown how CFTR senses pH(i). Here, we investigate the direct effects of pH(i)
      on recombinant CFTR using excised membrane patches. By altering channel gating,
      acidic pH(i) increased the open probability (P(o)) of wild-type CFTR, whereas
      alkaline pH(i) decreased P(o) and inhibited Cl(-) flow through the channel.
      Acidic pH(i) potentiated the MgATP dependence of wild-type CFTR by increasing
      MgATP affinity and enhancing channel activity, whereas alkaline pH(i) inhibited
      the MgATP dependence of wild-type CFTR by decreasing channel activity. Because
      these data suggest that pH(i) modulates the interaction of MgATP with the
      nucleotide-binding domains (NBDs) of CFTR, we examined the pH(i) dependence of
      site-directed mutations in the two ATP-binding sites of CFTR that are located at
      the NBD1:NBD2 dimer interface (site 1: K464A-, D572N-, and G1349D-CFTR; site 2:
      G551D-, K1250M-, and D1370N-CFTR). Site 2 mutants, but not site 1 mutants,
      perturbed both potentiation by acidic pH(i) and inhibition by alkaline pH(i),
      suggesting that site 2 is a critical determinant of the pH(i) sensitivity of
      CFTR. The effects of pH(i) also suggest that site 2 might employ substrate
      assisted catalysis to ensure that ATP hydrolysis follows NBD dimerization. We
      conclude that the CFTR Cl(-) channel senses directly pH(i). The direct regulation
      of CFTR by pH(i) has important implications for the regulation of epithelial ion
      transport.

PMID- 19837661
TI  - Heparan sulfate phage display antibodies identify distinct epitopes with complex
      binding characteristics: insights into protein binding specificities.
AB  - Heparan sulfate (HS) binds and modulates the transport and activity of a large
      repertoire of regulatory proteins. The HS phage display antibodies are powerful
      tools for the analysis of native HS structure in situ; however, their epitopes
      are not well defined. Analysis of the binding specificities of a set of HS
      antibodies by competitive binding assays with well defined chemically modified
      heparins demonstrates that O-sulfates are essential for binding; however,
      increasing sulfation does not necessarily correlate with increased antibody
      reactivity. IC50 values for competition with double modified heparins were not
      predictable from IC50 values with corresponding singly modified heparins. Binding
      assays and immunohistochemistry revealed that individual antibodies recognize
      distinct epitopes and that these are not single linear sequences but families of
      structurally similar motifs in which subtle variations in sulfation and
      conformation modify the affinity of interaction. Modeling of the antibodies
      demonstrates that they possess highly basic CDR3 and surrounding surfaces,
      presenting a number of possible orientations for HS binding. Unexpectedly, there
      are significant differences between the existence of epitopes in tissue sections
      and observed in vitro in dot blotted tissue extracts, demonstrating that in vitro
      specificity does not necessarily correlate with specificity in situ/vivo. The
      epitopes are therefore more complex than previously considered. Overall, these
      data have significance for structure-activity relationships of HS, because the
      model of one antibody recognizing multiple HS structures and the influence of
      other in situ HS-binding proteins on epitope availability are likely to reflect
      the selectivity of many HS-protein interactions in vivo.

PMID- 19837662
TI  - Identification of a novel L-serine analog that suppresses osteoclastogenesis in
      vitro and bone turnover in vivo.
AB  - Osteoclasts are multinucleated giant cells with bone resorbing activity. We
      previously reported that the expression of the transcription factor NFAT2
      (NFATc1) induced by receptor activator of NF-kappaB ligand (RANKL) is essential
      for the formation of multinucleated cells. We subsequently identified L-Ser in
      the differentiation medium as necessary for the expression of NFAT2. Here we
      searched for serine analogs that antagonize the function of L-Ser and suppress
      the formation of osteoclasts in bone marrow as well as RAW264 cells. An analog
      thus identified, H-Ser(tBu)-OMe x HCl, appeared to suppress the production of 3
      ketodihydrosphingosine by serine palmitoyltransferase, and the expression and
      localization of RANK, a cognate receptor of RANKL, in membrane lipid rafts was
      down-regulated in the analog-treated cells. The addition of lactosylceramide,
      however, rescued the osteoclastic formation. When administered in vivo, the
      analog significantly increased bone density in mice and prevented high bone
      turnover induced by treatment with soluble RANKL. These results demonstrate a
      close connection between the metabolism of L-Ser and bone remodeling and also the
      potential of the analog as a novel therapeutic tool for bone destruction.

PMID- 19837663
TI  - The matricellular protein periostin is required for sost inhibition and the
      anabolic response to mechanical loading and physical activity.
AB  - Periostin (gene Postn) is a secreted extracellular matrix protein involved in
      cell recruitment and adhesion and plays an important role in odontogenesis. In
      bone, periostin is preferentially expressed in the periosteum, but its functional
      significance remains unclear. We investigated Postn(-/-) mice and their wild type
      littermates to elucidate the role of periostin in the skeletal response to
      moderate physical activity and direct axial compression of the tibia.
      Furthermore, we administered a sclerostin-blocking antibody to these mice in
      order to demonstrate the influence of sustained Sost expression in their altered
      bone phenotypes. Cancellous and cortical bone microarchitecture as well as
      bending strength were altered in Postn(-/-) compared with Postn(+/+) mice.
      Exercise and axial compression both significantly increased bone mineral density
      and trabecular and cortical microarchitecture as well as biomechanical properties
      of the long bones in Postn(+/+) mice by increasing the bone formation activity,
      particularly at the periosteum. These changes correlated with an increase of
      periostin expression and a consecutive decrease of Sost in the stimulated bones.
      In contrast, mechanical stimuli had no effect on the skeletal properties of
      Postn(-/-) mice, where base-line expression of Sost levels were higher than
      Postn(+/+) and remained unchanged following axial compression. In turn, the
      concomitant injection of sclerostin-blocking antibody rescued the bone
      biomechanical response in Postn(-/-) mice. Taken together, these results indicate
      that the matricellular periostin protein is required for Sost inhibition and
      thereby plays an important role in the determination of bone mass and
      microstructural in response to loading.

PMID- 19837664
TI  - Disease-causing mutations in the cystic fibrosis transmembrane conductance
      regulator determine the functional responses of alveolar macrophages.
AB  - Alveolar macrophages (AMs) play a major role in host defense against microbial
      infections in the lung. To perform this function, these cells must ingest and
      destroy pathogens, generally in phagosomes, as well as secrete a number of
      products that signal other immune cells to respond. Recently, we demonstrated
      that murine alveolar macrophages employ the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl(-) channel as a determinant in lysosomal
      acidification (Di, A., Brown, M. E., Deriy, L. V., Li, C., Szeto, F. L., Chen,
      Y., Huang, P., Tong, J., Naren, A. P., Bindokas, V., Palfrey, H. C., and Nelson,
      D. J. (2006) Nat. Cell Biol. 8, 933-944). Lysosomes and phagosomes in murine
      cftr(-/-) AMs failed to acidify, and the cells were deficient in bacterial
      killing compared with wild type controls. Cystic fibrosis is caused by mutations
      in CFTR and is characterized by chronic lung infections. The information about
      relationships between the CFTR genotype and the disease phenotype is scarce both
      on the organismal and cellular level. The most common disease-causing mutation,
      DeltaF508, is found in 70% of patients with cystic fibrosis. The mutant protein
      fails to fold properly and is targeted for proteosomal degradation. G551D, the
      second most common mutation, causes loss of function of the protein at the plasma
      membrane. In this study, we have investigated the impact of CFTR DeltaF508 and
      G551D on a set of core intracellular functions, including organellar
      acidification, granule secretion, and microbicidal activity in the AM. Utilizing
      primary AMs from wild type, cftr(-/-), as well as mutant mice, we show a tight
      correlation between CFTR genotype and levels of lysosomal acidification,
      bacterial killing, and agonist-induced secretory responses, all of which would be
      expected to contribute to a significant impact on microbial clearance in the
      lung.

PMID- 19837665
TI  - Novel positive feedback loop between Cdk1 and Chk1 in the nucleus during G2/M
      transition.
AB  - Chk1, one of the critical transducers in DNA damage/replication checkpoints,
      prevents entry into mitosis through inhibition of Cdk1 activity. However, it has
      remained unclear how this inhibition is cancelled at the G(2)/M transition. We
      reported recently that Chk1 is phosphorylated at Ser(286) and Ser(301) by Cdk1
      during mitosis. Here, we show that mitotic Chk1 phosphorylation is accompanied by
      Chk1 translocation from the nucleus to the cytoplasm in prophase. This
      translocation advanced in accordance with prophase progression and was regulated
      by Crm-1-dependent nuclear export. Exogenous Chk1 mutated at Ser(286) and
      Ser(301) to Ala (S286A/S301A) was observed mainly in the nuclei of prophase
      cells, although such nuclear accumulation was hardly observed in wild-type Chk1.
      Induction of S286A/S301A resulted in the delay of mitotic entry. Biochemical
      analyses using immunoprecipitated cyclin B(1)-Cdk1 complexes revealed S286A/S301A
      expression to block the adequate activation of Cdk1. In support of this,
      S286A/S301A expression retained Wee1 at higher levels and Cdk1-induced
      phosphorylation of cyclin B(1) and vimentin at lower levels. A kinase-dead
      version of S286A/S301A also localized predominantly in the nucleus but lost the
      ability to delay mitotic entry. These results indicate that Chk1 phosphorylation
      by Cdk1 participates in cytoplasmic sequestration of Chk1 activity, which
      releases Cdk1 inhibition in the nucleus and promotes mitotic entry.

PMID- 19837666
TI  - Glyceraldehyde-3-phosphate dehydrogenase aggregate formation participates in
      oxidative stress-induced cell death.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)(2) is a classic glycolytic
      enzyme that also mediates cell death by its nuclear translocation under oxidative
      stress. Meanwhile, we previously presented that oxidative stress induced
      disulfide-bonded GAPDH aggregation in vitro. Here, we propose that GAPDH
      aggregate formation might participate in oxidative stress-induced cell death both
      in vitro and in vivo. We show that human GAPDH amyloid-like aggregate formation
      depends on the active site cysteine-152 (Cys-152) in vitro. In SH-SY5Y
      neuroblastoma, treatment with dopamine decreases the cell viability concentration
      dependently (IC(50) = 202 microM). Low concentrations of dopamine (50-100 microM)
      mainly cause nuclear translocation of GAPDH, whereas the levels of GAPDH
      aggregates correlate with high concentrations of dopamine (200-300 microM)
      induced cell death. Doxycycline-inducible overexpression of wild-type GAPDH in SH
      SY5Y, but not the Cys-152-substituted mutant (C152A-GAPDH), accelerates cell
      death accompanying both endogenous and exogenous GAPDH aggregate formation in
      response to high concentrations of dopamine. Deprenyl, a blocker of GAPDH nuclear
      translocation, fails to inhibit the aggregation both in vitro and in cells but
      reduced cell death in SH-SY5Y treated with only a low concentration of dopamine
      (100 microM). These results suggest that GAPDH participates in oxidative stress
      induced cell death via an alternative mechanism in which aggregation but not
      nuclear translocation of GAPDH plays a role. Moreover, we observe endogenous
      GAPDH aggregate formation in nigra-striatum dopaminergic neurons after
      methamphetamine treatment in mice. In transgenic mice overexpressing wild-type
      GAPDH, increased dopaminergic neuron loss and GAPDH aggregate formation are
      observed. These data suggest a critical role of GAPDH aggregates in oxidative
      stress-induced brain damage.

PMID- 19837667
TI  - Targeted knockdown of EGR-1 inhibits IL-8 production and IL-8-mediated invasion
      of prostate cancer cells through suppressing EGR-1/NF-kappaB synergy.
AB  - IL-8 produced by prostate cancer cells may be responsible for the androgen
      independent growth of advanced prostate cancers. Accumulating evidence from
      microarray analyses and animal genetic models highlights the central involvement
      of the transcription factor early growth response-1 (EGR-1) in prostate carcinoma
      progression. It is unknown, however, whether knockdown of EGR-1 inhibits IL-8
      production and IL-8-mediated tumor metastasis. Here we show that EGR-1 knockdown
      by a specific shRNA-Egr1 inhibited gene transcription and production of IL-8 by
      the human prostate cancer cell line DU145. Conversely, enforced expression of EGR
      1 in EGR-1-lacking PC3 prostate cancer cells markedly enhanced IL-8 transcription
      and secretion. By using wild type and a series of mutant IL-8 promoter luciferase
      constructs, we found that the NF-kappaB binding site is important for EGR-1
      regulation of IL-8. Furthermore, silencing EGR-1 suppressed a synergistically
      functional interaction between EGR-1 and NF-kappaB. Consequently, knockdown of
      EGR-1 inhibited IL-8-mediated tumor colony formation and invasion. Thus, targeted
      knockdown of EGR-1 could be an effective therapeutic approach against prostate
      cancer.

PMID- 19837668
TI  - Sensing domain dynamics in protein kinase A-I{alpha} complexes by solution X-ray
      scattering.
AB  - The catalytic (C) and regulatory (R) subunits of protein kinase A are
      exceptionally dynamic proteins. Interactions between the R- and C-subunits are
      regulated by cAMP binding to the two cyclic nucleotide-binding domains in the R
      subunit. Mammalian cells express four different isoforms of the R-subunit
      (RIalpha, RIbeta, RIIalpha, and RIIbeta) that all interact with the C-subunit in
      different ways. Here, we investigate the dynamic behavior of protein complexes
      between RIalpha and C-subunits using small angle x-ray scattering. We show that a
      single point mutation in RIalpha, R333K (which alters the cAMP-binding properties
      of Domain B) results in a compact shape compared with the extended shape of the
      wild-type R.C complex. A double mutant complex that disrupts the interaction site
      between the C-subunit and Domain B in RIalpha, RIalpha(AB)R333K.C(K285P), results
      in a broader P(r) curve that more closely resembles the P(r) profiles of wild
      type complexes. These results together suggest that interactions between RIalpha
      Domain B and the C-subunit in the RIalpha.C complex involve large scale dynamics
      that can be disrupted by single point mutations in both proteins. In contrast to
      RIalpha.C complexes. Domain B in the RIIbeta.C heterodimer is not dynamic and is
      critical for both inhibition and complex formation. Our study highlights the
      functional differences of domain dynamics between protein kinase A isoforms,
      providing a framework for elucidating the global organization of each holoenzyme
      and the cross-talk between the R- and C-subunits.

PMID- 19837669
TI  - Dynein light intermediate chain in Aspergillus nidulans is essential for the
      interaction between heavy and intermediate chains.
AB  - Cytoplasmic dynein is a complex containing heavy chains (HCs), intermediate
      chains (ICs), light intermediate chains (LICs), and light chains (LCs). The HCs
      are responsible for motor activity. The ICs at the tail region of the motor
      interact with dynactin, which is essential for dynein function. However,
      functions of other subunits and how they contribute to the assembly of the core
      complex are not clearly defined. Here, we analyzed in the filamentous fungus
      Aspergillus nidulans functions of the only LIC and two LCs, RobA (Roadblock/LC7)
      and TctexA (Tctex1) in dynein-mediated nuclear distribution (nud). Whereas the
      deletion mutant of tctexA did not exhibit an apparent nud mutant phenotype, the
      deletion mutant of robA exhibited a nud phenotype at an elevated temperature,
      which is similar to the previously characterized nudG (LC8) deletion mutant.
      Remarkably, in contrast to the single mutants, the robA and nudG double deletion
      mutant exhibits a severe nud phenotype at various temperatures. Thus, functions
      of these two LC classes overlap to some extent, but the presence of both becomes
      important under specific conditions. The single LIC, however, is essential for
      dynein function in nuclear distribution. This is evidenced by the identification
      of the nudN gene as the LIC coding gene, and by the nud phenotype exhibited by
      the LIC down-regulating mutant, alcA-LIC. Without a functional LIC, the HC-IC
      association is significantly weakened, and the HCs could no longer accumulate at
      the microtubule plus end. Thus, the LIC is essential for the assembly of the core
      complex of dynein in Aspergillus.

PMID- 19837670
TI  - MTA1 coregulator regulates p53 stability and function.
AB  - Although metastasis-associated protein 1 (MTA1) has recently been shown as a DNA
      damage responsive protein, the underlying mechanism for its role in DNA double
      strand break (DSB) repair remains unknown. Here, we show that MTA1 controls p53
      stability through inhibiting its ubiquitination by E3 ubiquitin ligases mouse
      double minute 2 (Mdm2) and constitutive photomorphogenic protein 1 (COP1). The
      underlying mechanisms involve the ability of MTA1 to compete with COP1 to bind to
      p53 and/or to destabilize COP1 and Mdm2. Consequently, MTA1 regulates the p53
      dependent transcription of p53R2, a direct p53 target gene for supplying
      nucleotides to repair damaged DNA. Depletion of MTA1 impairs p53-dependent p53R2
      transcription and compromises DNA repair. Interestingly, these events could be
      reversed by MTA1 reintroduction, indicating that MTA1 interjects into the p53
      dependent DNA repair. Given the fact that MTA1 is widely up-regulated in human
      cancers, these findings in conjunction with our earlier finding of a crucial role
      of MTA1 in DSB repair suggest an inherent role of the MTA1-p53-p53R2 pathway in
      DNA damage response in cancer cells.

PMID- 19837671
TI  - HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through
      transmembrane interactions leading to lysosomes.
AB  - Bone marrow stromal antigen 2 (BST-2, also known as tetherin) is a recently
      identified interferon-inducible host restriction factor that can block the
      production of enveloped viruses by trapping virus particles at the cell surface.
      This antiviral effect is counteracted by the human immunodeficiency virus type 1
      (HIV-1) accessory protein viral protein U (Vpu). Here we show that HIV-1 Vpu
      physically interacts with BST-2 through their mutual transmembrane domains and
      leads to the degradation of this host factor via a lysosomal, not proteasomal,
      pathway. The degradation is partially controlled by a cellular protein, beta
      transducin repeat-containing protein (betaTrCP), which is known to be required
      for the Vpu-induced degradation of CD4. Importantly, targeting of BST-2 by Vpu
      occurs at the plasma membrane followed by the active internalization of this host
      protein by Vpu independently of constitutive endocytosis. Thus, the primary site
      of action of Vpu is the plasma membrane, where Vpu targets and internalizes cell
      surface BST-2 through transmembrane interactions, leading to lysosomal
      degradation, partially in a betaTrCP-dependent manner. Also, we propose the
      following configuration of BST-2 in tethering virions to the cell surface; each
      of the dimerized BST-2 molecules acts as a bridge between viral and cell
      membranes.

PMID- 19837672
TI  - ADP but not P(i) dissociation contributes to rate limitation for Escherichia coli
      Rho.
AB  - To define the molecular mechanism by which ATP hydrolysis powers the 5'-->3'
      travel of homohexameric Escherichia coli transcription termination factor Rho
      along RNA, rates for association and dissociation of non-RNA substrates and
      products were measured. Rapid mix/chemical quench and stopped-flow
      spectrofluorometry measurements were carried out with Rho and [gamma-(32)P]ATP,
      mantADP, or fluorescently tagged E. coli phosphate-binding protein. The results
      indicate that the P(i) off-rate is not rate limiting, but at approximately 90 s(
      1), the ADP dissociation rate is comparable to the 30 s(-1) k(cat). Previous
      results indicate that the chemistry step of ATP hydrolysis by Rho is at least 10
      fold faster than the overall catalytic cycle. The as yet unmeasured RNA
      dissociation step, which could be associated with a protein conformation change,
      might also be a rate-limiting factor.

PMID- 19837674
TI  - Ligand effects on cross-linking support a conformational mechanism for serotonin
      transport.
AB  - Serotonin transporter (SERT) is responsible for the re-uptake of 5
      hydroxytryptamine (5-HT) from the synaptic cleft after release from serotonergic
      neurons. We show here that cysteine residues at positions in transmembranes 1 and
      3 of SERT, like the corresponding positions in the gamma-aminobutyric acid
      transporter, can be cross-linked using copper(II)(1,10-phenanthroline)(3). The
      presence of a cross-link was detected by a novel methionine mutagenesis strategy.
      A change in mobility for an N-terminal cyanogen bromide fragment accompanied
      disulfide cross-linking of the two cysteine residues. Cross-linking also
      inhibited transport, and this process was blocked by cocaine, which is expected
      to stabilize SERT in conformations where the two positions are separated, but
      cocaine did not decrease accessibility of either of the two cysteines to
      modification by 2-aminoethyl methanethiosulfonate. Cysteine was required at both
      positions on the same molecule for efficient cross-linking, indicating that the
      reaction was intramolecular.

PMID- 19837673
TI  - Mechanism of inhibition of HIV-1 reverse transcriptase by 4'-Ethynyl-2-fluoro-2'
      deoxyadenosine triphosphate, a translocation-defective reverse transcriptase
      inhibitor.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are employed in first line
      therapies for the treatment of human immunodeficiency virus (HIV) infection. They
      generally lack a 3'-hydroxyl group, and thus when incorporated into the nascent
      DNA they prevent further elongation. In this report we show that 4'-ethynyl-2
      fluoro-2'-deoxyadenosine (EFdA), a nucleoside analog that retains a 3'-hydroxyl
      moiety, inhibited HIV-1 replication in activated peripheral blood mononuclear
      cells with an EC(50) of 0.05 nm, a potency several orders of magnitude better
      than any of the current clinically used NRTIs. This exceptional antiviral
      activity stems in part from a mechanism of action that is different from approved
      NRTIs. Reverse transcriptase (RT) can use EFdA-5'-triphosphate (EFdA-TP) as a
      substrate more efficiently than the natural substrate, dATP. Importantly, despite
      the presence of a 3'-hydroxyl, the incorporated EFdA monophosphate (EFdA-MP)
      acted mainly as a de facto terminator of further RT-catalyzed DNA synthesis
      because of the difficulty of RT translocation on the nucleic acid primer
      possessing 3'-terminal EFdA-MP. EFdA-TP is thus a translocation-defective RT
      inhibitor (TDRTI). This diminished translocation kept the primer 3'-terminal EFdA
      MP ideally located to undergo phosphorolytic excision. However, net
      phosphorolysis was not substantially increased, because of the apparently facile
      reincorporation of the newly excised EFdA-TP. Our molecular modeling studies
      suggest that the 4'-ethynyl fits into a hydrophobic pocket defined by RT residues
      Ala-114, Tyr-115, Phe-160, and Met-184 and the aliphatic chain of Asp-185. These
      interactions, which contribute to both enhanced RT utilization of EFdA-TP and
      difficulty in the translocation of 3'-terminal EFdA-MP primers, underlie the
      mechanism of action of this potent antiviral nucleoside.

PMID- 19837675
TI  - Profiling carbohydrate-receptor interaction with recombinant innate immunity
      receptor-Fc fusion proteins.
AB  - The recognition of bacteria, viruses, fungi, and other microbes is controlled by
      host immune cells, which are equipped with many innate immunity receptors, such
      as Toll-like receptors, C-type lectin receptors, and immunoglobulin-like
      receptors. Our studies indicate that the immune modulating properties of many
      herbal drugs, for instance, the medicinal fungus Reishi (Ganoderma lucidum) and
      Cordyceps sinensis, could be attributed to their polysaccharide components. These
      polysaccharides specifically interact with and activate surface receptors
      involved in innate immunity. However, due to the complexity of polysaccharides
      and their various sources from medicinal fungi, quantitative analysis of
      medicinal polysaccharide extracts with regard to their functions represents a
      major challenge. To profile carbohydrate-immune receptor interactions, the
      extracellular domains of 17 receptors were cloned as Fc-fusion proteins, such
      that their interactions with immobilized polysaccharides could be probed in an
      enzyme-linked immunosorbent assay. The results show that several innate immune
      receptors, including Dectin-1, DC-SIGN, Langerin, Kupffer cell receptor,
      macrophage mannose receptor, TLR2, and TLR4, interact with the polysaccharide
      extracts from G. lucidum (GLPS). This analysis revealed distinct polysaccharide
      profiles from different sources of medicinal fungi, and the innate immune
      receptor-based enzyme-linked immunosorbent assay described here can serve as a
      high-throughput profiling method for the characterization and quality control of
      medicinal polysaccharides. It also provides a means to dissect the molecular
      mechanism of medicinal polysaccharide-induced immunomodulation events.

PMID- 19837676
TI  - Regulation of transforming growth factor-beta-dependent cyclooxygenase-2
      expression in fibroblasts.
AB  - Abnormal transforming growth factor-beta (TGF-beta) signaling is a critical
      contributor to the pathogenesis of various human diseases ranging from tissue
      fibrosis to tumor formation. Excessive TGF-beta signaling stimulates fibrotic
      responses. Recent research has focused in the main on the antiproliferative
      effects of TGF-beta in fibroblasts, and it is presently understood that TGF-beta
      stimulated cyclooxygenase-2 (COX-2) induction in fibroblasts is essential for
      antifibroproliferative effects of TGF-beta. Both TGF-beta and COX-2 have been
      implicated in tumor growth, invasion, and metastasis, and therefore tumor
      associated fibroblasts are a recent topic of interest. Here we report the
      identification of positive and negative regulatory factors of COX-2 expression
      induced by TGF-beta as determined using proteomic approaches. We show that TGF
      beta coordinately up-regulates three factors, heterogeneous nuclear
      ribonucleoprotein A/B (HNRPAB), nucleotide diphosphate kinase A (NDPK A), and
      nucleotide diphosphate kinase A (NDPK B). Functional pathway analysis showed that
      HNRPAB augments mRNA and protein levels of COX-2 and subsequent prostaglandin
      E(2) (PGE(2)) production by suppressing degradation of COX-2 mRNA. In contrast,
      NDPK A and NDPK B attenuated mRNA and protein levels of COX-2 by affecting TGF
      beta-Smad2/3/4 signaling at the receptor level. Collectively, we report on a new
      regulatory pathway of TGF-beta in controlling expression of COX-2 in fibroblasts,
      which advances our understanding of pathophysiological mechanisms of TGF-beta.

PMID- 19837677
TI  - Nod2 regulates the host response towards microflora by modulating T cell function
      and epithelial permeability in mouse Peyer's patches.
AB  - Nucleotide oligomerisation domain 2 (NOD2) mutations are associated with
      susceptibility to Crohn's disease and graft-versus-host disease, two human
      disorders related with dysfunctions of Peyer's patches (PPs). In Nod2(-/-) mice
      transcellular permeability and bacterial translocation are increased in PPs. In
      this study, we show that both anti-CD4(+) and anti-interferon gamma (anti
      IFNgamma) monoclonal antibodies abrogate this phenotype and reduce the expression
      of tumour necrosis factor (TNF) receptor 2 and the long isoform of myosin light
      chain kinase, thus demonstrating that immune T cells influence the epithelial
      functions. In turn, intraperitoneal injection of ML-7 (a myosin light chain
      kinase inhibitor) normalises the values of CD4(+) T cells, IFNgamma and TNFalpha.
      This reciprocal cross-talk is under the control of the gut microflora as shown by
      the normalisation of all parameters after antibiotic treatment. Toll-like
      receptor 2 (TLR2) and TLR4 expression were increased in Nod2(-/-) mice under
      basal conditions and TLR2 and TLR4 agonists induced an increased transcellular
      permeability in Nod2(+/+) mice. Muramyldipeptide (a Nod2 agonist) or ML-7 was
      able to reverse this phenomenon. It thus appears that Nod2 modulates the cross
      talk between CD4(+) T cells and the epithelium recovering PP and that it
      downregulates the pro-inflammatory effect driven by the ileal microflora, likely
      by inhibiting the TLR pathways.

PMID- 19837678
TI  - Low cardiac output predicts development of hepatorenal syndrome and survival in
      patients with cirrhosis and ascites.
AB  - OBJECTIVES: Recent studies suggest that cardiac dysfunction precedes development
      of the hepatorenal syndrome. In this follow-up study, we aimed to investigate the
      relation between cardiac and renal function in patients with cirrhosis and
      ascites and the impact of cardiac systolic function on survival. PATIENTS AND
      DESIGN: Twenty-four patients with cirrhosis and ascites were included. Cardiac
      function was investigated by gated myocardial perfusion imaging (MPI) for
      assessment of cardiac index (CI) and cardiac volumes. The renal function was
      assessed by determination of glomerular filtration rate (GFR) and renal blood
      flow (RBF) and the patients were followed up for 12 months. RESULTS: In patients
      with a CI below 1.5 l/min/m(2) on MPI, GFR was lower (39 (SD 24) vs 63 (SD 23)
      ml/min, p = 0.03), RBF was lower (352 (SD 232) vs 561 (SD 229) ml/min, p = 0.06),
      and serum creatinine was higher (130 (SD 46) vs 78 (SD 29) mumol/l, p<0.01). The
      number of patients who developed hepatorenal syndrome type 1 within 3 months was
      higher in the group with low CI than in the high CI group (43% vs 5%, p = 0.04).
      Patients with the lowest CI (N = 8) had significantly poorer survival at 3, 9,
      and 12 months compared to those with a higher CI (N = 16), p<0.05. In contrast,
      the Model for End-stage Liver Disease (MELD) score failed to predict mortality in
      these patients. CONCLUSIONS: The development of renal failure and poor outcome in
      patients with advanced cirrhosis and ascites seem to be related to a cardiac
      systolic dysfunction. Other parameters may be more important than MELD score to
      predict prognosis.

PMID- 19837679
TI  - Visceral fat area is an independent predictive biomarker of outcome after first
      line bevacizumab-based treatment in metastatic colorectal cancer.
AB  - BACKGROUND: Adipose tissue releases angiogenic factors that may promote tumour
      growth. OBJECTIVE: To determine whether body mass index (BMI), subcutaneous fat
      area (SFA) and visceral fat area (VFA) are associated with outcomes in patients
      given first-line bevacizumab-based treatment for metastatic colorectal cancer
      (MCC). Patients CT was used to measure SFA and VFA in 120 patients with MCC who
      received bevacizumab-based treatment (bevacizumab group, n=80) or chemotherapy
      alone (chemotherapy group, n=40) as first-line treatment. Associations linking
      BMI, SFA and VFA to tumour response, time-to-progression (TTP) and overall
      survival (OS) were evaluated. RESULTS: In the bevacizumab group, median follow-up
      lasted for 24 months (3-70). BMI, SFA and VFA values above the median (ie, high
      BMI, high VFA and high SFA) were significantly associated with absence of a
      response. TTP was shorter in patients with high BMI (9 vs 12 months; p=0.01) or
      high VFA (9 vs 14 months; p=0.0008). High VFA was associated with shorter OS
      (p=0.0493). By multivariate analysis, high VFA was independently associated with
      response, TTP and OS (HR=7.18, p=0.008, HR=5.79, p=0.005 and HR=2.88, p=0.027,
      respectively). In the chemotherapy group, median follow-up lasted for 30 months
      (4-84). BMI, SFA and VFA were not associated with response, TTP or OS. In the
      whole population, interaction between VFA and bevacizumab administration was
      significant for response (OR=3.31, p=0.005) and TTP (HR=1.64, p=0.022), thereby
      confirming the results. CONCLUSION: This study provides the first evidence that
      high VFA independently predicts a poorer outcome in patients given first-line
      bevacizumab-based treatment for MCC. However, this predictive biomarker needs to
      be validated in a different dataset.

PMID- 19837680
TI  - The spectrum of MEFV clinical presentations--is it familial Mediterranean fever
      only?
AB  - OBJECTIVE: FMF is an autosomal recessive hereditary disease, associated with a
      single gene named MEFV. This gene is considered to be responsible only for FMF.
      In the present study, we tried to find out whether the MEFV gene is associated
      with or responsible for clinical conditions other than FMF. METHODS: We looked
      for patients who presented with signs and symptoms not typical for FMF but
      carried MEFV mutations. We also searched for reports about similar conditions in
      the English medical literature, and we surveyed the website 'Infevers' for MEFV
      mutations defined as associated with 'atypical FMF'. RESULTS: We encountered
      three patients carrying MEFV mutations who presented with distinct clinical
      presentations not typical of FMF. We identified additional reports about MEFV
      related non-FMF disease entities such as palindromic rheumatism. By screening the
      'Infevers' website, we further disclosed 13 cases with MEFV mutations that were
      defined as 'atypical FMF' and 4 cases categorized as 'recurrent arthritis'.
      CONCLUSIONS: These findings suggest that the MEFV gene is associated with
      clinical conditions other than FMF. Changing our concept regarding the MEFV gene
      and its link to such clinical phenotypes may call for a higher awareness of the
      existence of additional autoinflammatory diseases. Furthermore, a correct
      diagnosis of these MEFV gene mutation-associated syndromes will justify a
      therapeutic trial with colchicine, thereby relieving suffering of many patients
      who up to now have been misdiagnosed.

PMID- 19837682
TI  - Atrial fibrillation and long-term prognosis in patients hospitalized for heart
      failure: results from heart failure survey in Israel (HFSIS).
AB  - AIMS: Atrial fibrillation (AF) and heart failure (HF) commonly coexist, and each
      adversely affects the other. The aim of the study was to prospectively evaluate
      the impact of AF and its subtypes on management, and early and long-term outcome
      of hospitalized HF patients. METHODS AND RESULTS: Data were prospectively
      collected on HF patients hospitalized in all public hospitals in Israel as part
      of a national survey (HFSIS). Atrial fibrillation patients were subdivided into
      intermittent and chronic AF subgroups. During March-April 2003, we enrolled 4102
      HF patients, of whom 1360 (33.2%) had AF [600 (44.1%) intermittent, 562 (41.3%)
      chronic]. Patients with AF were older (76.9 +/- 10.5 vs. 71.7 +/- 12.6 years, P =
      0.0001), males, with preserved LV systolic function. Crude mortality rates for AF
      patients were progressively and consistently higher during hospitalization and
      during the 4-year follow-up period, especially in the chronic AF group (P =
      0.0001). After covariate adjustment, AF was associated with increased 1-year
      mortality [HR 1.19, 95% CI (1.03-1.36)]. CONCLUSION: AF was present in a third of
      hospitalized HF patients, and identified a population with increased mortality
      risk, largely due to co-morbidities.

PMID- 19837683
TI  - A state indicator on regional scale for high-voltage power lines: defining a
      priority for in situ inspections.
AB  - An integrated system to evaluate the magnetic field generated by power lines
      exposure has been developed using a specific simulation model (PLEIA-EMF). This
      is part of a software toolset, subjected to internal suitability verifications
      and in-field validations. A state indicator related to each span has been
      determined using the data extracted from digital cartography, the magnetic field
      calculated by PLEIA and the number of people living in the nearest buildings. In
      this way, it is possible to determine eventual criticalities in the considered
      area, focusing attention on those cases with more considerable exposure levels
      and involving a higher number of people. A campaign of inspections has been
      planned using PLEIA simulations. The reliability of stored technical data and the
      real population exposure levels have been evaluated in critical cases,
      individuated through the following described methodology. The procedures leading
      to the indicator determination and the modalities of in situ inspections are here
      presented.

PMID- 19837684
TI  - Can differences in IVF success rates between centres be explained by patient
      characteristics and sample size?
AB  - BACKGROUND: Pregnancy rates cannot be used reliably for comparison of IVF clinic
      performance because of differences in patients between clinics. We investigate if
      differences in pregnancy chance between IVF centres remain after adjustment for
      patient mix. METHODS: We prospectively collected IVF and ICSI treatment data from
      11 out of 13 IVF centres in the Netherlands, between 2002 and 2004. Adjustment
      for sampling variation was made using a random effects model. A prognostic index
      for subfertility-related factors was used to adjust for differences in patient
      mix. The remaining variability between centres was split into random variation
      and true differences. RESULTS: The crude 1-year ongoing pregnancy chance per
      centre differed by nearly a factor 3 between centres, with hazard ratios (HRs) of
      0.48 (95% CI: 0.34-0.69) to 1.34 (95% CI: 1.18-1.51) compared with the mean 1
      year ongoing pregnancy chance of all centres. After accounting for sampling
      variation, the difference shrank since HRs became 0.66 (95% CI: 0.51-0.85) to
      1.28 (95% CI: 1.13-1.44). After adjustment for patient mix, the difference
      narrowed somewhat further to HRs of 0.74 (95% CI: 0.57-0.94) to 1.33 (95% CI:
      1.20-1.48) and 17% of the variation between centres could be explained by patient
      mix. The 1-year cumulative ongoing pregnancy rate in the two most extreme centres
      was 36% and 55%. CONCLUSIONS: Only a minor part of the differences in pregnancy
      chance between IVF centres is explained by patient mix. Further research is
      needed to elucidate the causes of the remaining differences.

PMID- 19837685
TI  - Type I and type II pathways of Fas-mediated apoptosis are differentially
      controlled by XIAP.
AB  - The mechanism by which Fas activates the apoptotic pathway differs in so-called
      type I and type II cells. X chromosome-linked inhibitor of apoptosis protein has
      now been revealed as an important molecule that is differentially regulated in
      type I vs. type II cells.

PMID- 19837686
TI  - Sensorium: the original raison d'etre of the motile cilium?
AB  - The role of non-motile (primary) cilia as sensory antennae critical for metazoan
      development and physiology has surfaced over the last decade, long after the
      function of motile cilia in propelling cells or moving fluids across tissues was
      well established. A new study of motile cilia from respiratory airways raises the
      possibility that transducing sensory cues from the environment is a universal
      characteristic of cilia and may have been the original raison d'etre of the
      ancestral cilium.

PMID- 19837687
TI  - Autofluorescence imaging videobronchoscopy improves assessment of tumor margins
      and affects therapeutic strategy in central lung cancer.
AB  - OBJECTIVE: Autofluorescence imaging (AFI) videobronchoscopy is a new endoscopic
      tool that improves visualization of neoplastic changes in the bronchial mucosa.
      The major aim of our study was to determine sensitivity and specificity of the
      technique in the assessment of tumor extent (margins). The secondary objective
      was to evaluate the possible effect of AFI on the change in therapeutic decisions
      of lung cancer treatment. METHODS: In this prospective trial, we enrolled 104
      patients in whom we performed 624 targeted biopsies, 3 from the pathologically
      altered mucosa (red-brownish or magenta colored) and 3 from randomly picked
      normal areas. We were using the Olympus BF-F260 videobronchoscope and EVIS LUCERA
      system. White light videobronchoscopy (WLB) preceded AFI examination and biopsy
      collection. All biopsy specimens were examined by a pathologist blinded to
      bronchoscopy findings, and where applicable surgically resected specimens were
      examined. RESULTS: In 14.4% of the patients, AFI revealed a greater extent of the
      tumor than WLB, and in 11.5% that finding led to change in therapeutic decision
      (lesser or greater resection or avoidance of surgery). We found a significant
      correlation between tumor extent determined by AFI and changes in therapeutic
      decisions (P < 0.01). Sensitivity, specificity, positive predictive value and
      negative predictive value for AFI in the assessment of tumor extension were 93%,
      92%, 92% and 93%, respectively. Corresponding results for WLB were 84%, 79%, 77%
      and 85%, respectively. Relative sensitivity of AFI is 1.11. CONCLUSIONS: Our
      results confirm that AFI videobronchoscopy significantly improves the assessment
      of central lung cancer extension and influences the therapeutic strategy. This
      technique has greater sensitivity and specificity, in assessment of tumor
      margins, than WLB alone.

PMID- 19837688
TI  - Prognostic stratification in patients who received hormonal therapy for prostate
      specific antigen recurrence after radical prostatectomy.
AB  - The present study was undertaken to investigate the predictors in patients who
      received hormonal therapy (HT) for prostate-specific antigen recurrence (PSAR)
      after surgery. Predictors for the progression-free survival were assessed in 55
      patients who received HT for PSAR after surgery. In multivariate analysis,
      primary Gleason grade > or =4 and PSA doubling time (PSA-DT) <6 months were
      independent predictors. The patients were stratified into low-risk group (Gleason
      grade <4 and PSA-DT > or =6), high-risk group (Gleason grade > or =4 and PSA-DT
      <6) and intermediate-risk group (all others). In the intermediate- and high-risk
      groups, progression-free survival rate was significantly higher in patients with
      PSA level <2 than in those with PSA level > or =2 at the initiation of HT.
      Primary Gleason grade > or =4 and PSA-DT <6 months are independent predictors.
      Patients in the intermediate- and high-risk groups may benefit from early HT for
      PSAR after surgery.

PMID- 19837689
TI  - Docetaxel in combination with prednisolone for hormone refractory prostate
      cancer.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and toxicity
      of docetaxel in combination with prednisolone in Japanese patients with hormone
      refractory prostate cancer. METHODS: Twenty patients with hormone refractory
      prostate cancer (HRPC) were administered a treatment regimen consisting of
      docetaxel 75 mg/m(2) once every 3 or 4 weeks and prednisolone 5 mg twice daily at
      our institution between 2006 and 2008. RESULTS: The patients received a median of
      5.5 cycles of treatment (range, 2-12 cycles). Nine of the 20 patients (45%) had a
      >or=50% decrease in serum prostate-specific antigen (PSA). The median duration of
      response was 4 months (range, 1-11 months). The number of cycles performed, the
      presence of bone metastasis and the extent of disease had statistically
      significant associations with the response. Three patients had a transient PSA
      rise among the patients who ultimately had a response. Grade 3/4 leukopenia and
      neutropenia occurred in 80.0% and 85.0% of the patients, respectively.
      Interstitial pneumonia occurred in only one patient; however, the patient
      recovered. Finally, no treatment-related deaths were seen during the observation
      period. CONCLUSIONS: The combination of docetaxel 75 mg/m(2) every 3 weeks and
      prednisolone 10 mg daily was effective and well tolerated in Japanese patients
      with HRPC. The results of this study suggest that a decision concerning
      discontinuation of this treatment should be carefully considered because a
      transient PSA rise was observed. Although interstitial pneumonia was rare, the
      potential risk of its development should be taken into consideration.

PMID- 19837690
TI  - Cisplatin and etoposide chemotherapy combined with early concurrent twice-daily
      thoracic radiotherapy for limited-disease small cell lung cancer in elderly
      patients.
AB  - OBJECTIVE: The optimal management of elderly patients with limited-disease small
      cell lung cancer (LD-SCLC) has not been established. METHODS: The records of
      elderly (>or=70 years of age) patients with LD-SCLC who had been treated with
      etoposide and cisplatin chemotherapy with early concurrent twice-daily thoracic
      radiotherapy (TRT) were reviewed retrospectively. RESULTS: Of the 25 elderly
      patients with LD-SCLC identified, 12 (48%) individuals received etoposide
      cisplatin chemotherapy with early concurrent twice-daily TRT. The main toxicities
      of this treatment regimen were hematologic, with neutropenia of Grade 4 being
      observed in all patients and febrile neutropenia of Grade 3 in eight patients
      during the first cycle of chemoradiotherapy. The toxicity of TRT was acceptable,
      with all patients completing the planned radiotherapy within a median of 29 days
      (range, 19-33). No treatment-related deaths were observed. The median progression
      free survival and overall survival times were 14.2 months (95% confidence
      interval, 4.3-18.2) and 24.1 months (95% confidence interval, 11.3-27.2),
      respectively. CONCLUSIONS: Etoposide-cisplatin chemotherapy with early concurrent
      twice-daily TRT was highly myelotoxic in elderly patients with LD-SCLC, although
      no treatment-related deaths were observed in our cohort. Prospective studies are
      required to establish the optimal schedule and dose of chemotherapy and TRT in
      such patients.

PMID- 19837691
TI  - Co-evolution of KIR2DL3 with HLA-C in a human population retaining minimal
      essential diversity of KIR and HLA class I ligands.
AB  - Natural killer (NK) cells contribute to immunity and reproduction. Guiding these
      functions, and NK cell education, are killer cell Ig-like receptors (KIR), NK
      cell receptors that recognize HLA class I. In most human populations, these
      highly polymorphic receptors and ligands combine with extraordinary diversity. To
      assess how much of this diversity is necessary, we studied KIR and HLA class I at
      high resolution in the Yucpa, a small South Amerindian population that survived
      an approximate 15,000-year history of population bottleneck and epidemic
      infection, including recent viral hepatitis. The Yucpa retain the three major HLA
      epitopes recognized by KIR. Through balancing selection on a few divergent
      haplotypes the Yucpa maintain much of the KIR variation found worldwide. HLA
      C*07, the strongest educator of C1-specific NK cells, has reached unusually high
      frequency in the Yucpa. Concomitantly, weaker variants of the C1 receptor,
      KIR2DL3, were selected and have largely replaced the form of KIR2DL3 brought by
      the original migrants from Asia. HLA-C1 and KIR2DL3 homozygosity has previously
      been correlated with resistance to viral hepatitis. Selection of weaker forms of
      KIR2DL3 in the Yucpa can be seen as compensation for the high frequency of the
      potent HLA-C*07 ligand. This study provides an estimate of the minimal KIR-HLA
      system essential for long-term survival of a human population. That it contains
      all functional elements of KIR diversity worldwide, attests to the competitive
      advantage it provides, not only for surviving epidemic infections, but also for
      rebuilding populations once infection has passed.

PMID- 19837692
TI  - Msh2-dependent DNA repair mitigates a unique susceptibility of B cell progenitors
      to c-Myc-induced lymphomas.
AB  - C-Myc is one of the most common targets of genetic alterations in human cancers.
      Although overexpression of c-Myc in the B cell compartment predisposes to
      lymphomas, secondary mutations are required for disease manifestation. In this
      article, we show that genetic deficiencies causing arrested B cell development
      and accumulation of B cell progenitors lead to accelerated lymphomagenesis in Emu
      c-myc transgenic mice. This result suggests that B cell progenitors are more
      prone than their mature counterparts to developing secondary oncogenic lesions
      that complement c-Myc in promoting transformation. To investigate the nature of
      these oncogenic lesions, we examined Emu c-myc mice deficient in mismatch repair
      function. We report that Msh2(-/-) Emu c-myc and Msh2(G674A/G674A) Emu c-myc mice
      rapidly succumb to pro-B cell stage lymphomas, indicating that Msh2-dependent
      mismatch repair function actively suppresses c-Myc-associated oncogenesis during
      early B cell development.

PMID- 19837693
TI  - Alzheimer's disease-like pathological features in transgenic mice expressing the
      APP intracellular domain.
AB  - The hypothesis that amyloid-beta (Abeta) peptides are the primary cause of
      Alzheimer's disease (AD) remains the best supported theory of AD pathogenesis.
      Yet, many observations are inconsistent with the hypothesis. Abeta peptides are
      generated when amyloid precursor protein (APP) is cleaved by presenilins, a
      process that also produces APP intracellular domain (AICD). We previously
      generated AICD-overexpressing transgenic mice that showed abnormal activation of
      GSK-3beta, a pathological feature of AD. We now report that these mice exhibit
      additional AD-like characteristics, including hyperphosphorylation and
      aggregation of tau, neurodegeneration and working memory deficits that are
      prevented by treatment with lithium, a GSK-3beta inhibitor. Consistent with its
      potential role in AD pathogenesis, we find AICD levels to be elevated in brains
      from AD patients. The in vivo findings that AICD can contribute to AD pathology
      independently of Abeta have important therapeutic implications and may explain
      some observations that are discordant with the amyloid hypothesis.

PMID- 19837694
TI  - Evolutionary maintenance of selfish homing endonuclease genes in the absence of
      horizontal transfer.
AB  - Homing endonuclease genes are "selfish" mobile genetic elements whose
      endonuclease promotes the spread of its own gene by creating a break at a
      specific target site and using the host machinery to repair the break by copying
      and inserting the gene at this site. Horizontal transfer across the boundary of a
      species or population within which mating takes place has been thought to be
      necessary for their evolutionary persistence. This is based on the assumption
      that they will become fixed in a host population, where opportunities of homing
      will disappear, and become susceptible to degeneration. To test this hypothesis,
      we modeled behavior of a homing endonuclease gene that moves during meiosis
      through double-strand break repair. We mathematically explored conditions for
      persistence of the homing endonuclease gene and elucidated their parameter
      dependence as phase diagrams. We found that, if the cost of the pseudogene is
      lower than that of the homing endonuclease gene, the 2 forms can persist in a
      population through autonomous periodic oscillation. If the cost of the pseudogene
      is higher, 2 types of dynamics appear that enable evolutionary persistence:
      bistability dependent on initial frequency or fixation irrespective of initial
      frequency. The prediction of long persistence in the absence of horizontal
      transfer was confirmed by stochastic simulations in finite populations. The
      average time to extinction of the endonuclease gene was found to be thousands of
      meiotic generations or more based on realistic parameter values. These results
      provide a solid theoretical basis for an understanding of these and other
      extremely selfish elements.

PMID- 19837697
TI  - Mice lacking the glutamate-cysteine ligase modifier subunit are susceptible to
      myocardial ischaemia-reperfusion injury.
AB  - AIMS: Glutamate-cysteine ligase (GCL), a rate-limiting enzyme for glutathione
      (GSH) synthesis, is composed of catalytic and modifier subunits. This study
      examined the pathogenic role of GCL modifier subunits (GCLM) in myocardial
      ischaemia-reperfusion (I/R) injury using mice lacking the GCLM (GCLM(-/-)).
      METHODS AND RESULTS: The GCLM(-/-)mice had an increase in myocardial I/R injury
      and apoptosis in ischaemic myocardium compared with GCLM(+/+) mice. There was a
      decrease in mitochondrial glutathione (GSH) levels in ischaemic myocardium that
      was more pronounced in GCLM(-/-) mice than in GCLM(+/+) mice (12 vs. 55% of
      baseline GCLM(+/+), respectively). The ESR signal intensity of the dimethyl-1
      pyrroline-N-oxide-hydroxyl radical adducts in ischaemic myocardium was higher in
      GCLM(-/-) mice than in GCLM(+/+) mice. Hypoxia-reoxygenation induced greater
      mitochondrial damage in cultured cardiomyocytes from GCLM(-/-) mice than from
      GCLM(+/+) mice, as evidenced by a reduced membrane potential and increased
      protein carbonyl content in isolated mitochondria, together with enhanced
      cytochrome c translocation into the cytosol. Administration of GSH ethyl-ester
      attenuated myocardial I/R injury and reversed the mitochondrial damage in
      parallel with the mitochondrial GSH restoration in the myocardium or the
      cardiomyocytes of GCLM(-/-) mice. CONCLUSION: GCLM(-/-) mice were susceptible to
      myocardial I/R injury partly through an increased vulnerability of mitochondria
      to oxidative damage owing to mitochondrial GSH reduction.

PMID- 19837698
TI  - Analysis of mouse models of cytochrome c oxidase deficiency owing to mutations in
      Sco2.
AB  - Mutations in SCO2, a protein required for the proper assembly and functioning of
      cytochrome c oxidase (COX; complex IV of the mitochondrial respiratory chain),
      cause a fatal infantile cardioencephalomyopathy with COX deficiency. We have
      generated mice harboring a Sco2 knock-out (KO) allele and a Sco2 knock-in (KI)
      allele expressing an E-->K mutation at position 129 (E129K), corresponding to the
      E140K mutation found in almost all human SCO2-mutated patients. Whereas
      homozygous KO mice were embryonic lethals, homozygous KI and compound
      heterozygous KI/KO mice were viable, but had muscle weakness; biochemically, they
      had respiratory chain deficiencies as well as complex IV assembly defects in
      multiple tissues. There was a concomitant reduction in mitochondrial copper
      content, but the total amount of copper in examined tissues was not reduced.
      These mouse models should be of use in further studies of Sco2 function, as well
      as in testing therapeutic approaches to treat the human disorder.

PMID- 19837699
TI  - Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human
      primate.
AB  - Metachromatic leukodystrophy (MLD) is a lethal neurodegenerative disease caused
      by a deficiency in the lysosomal arylsulfatase A (ARSA) enzyme leading to the
      accumulation of sulfatides in glial and neuronal cells. We previously
      demonstrated in ARSA-deficient mice that intracerebral injection of a serotype 5
      adeno-associated vector (AAV) encoding human ARSA corrects the biochemical,
      neuropathological and behavioral abnormalities. However, before considering a
      potential clinical application, scaling-up issues should be addressed in large
      animals. Therefore, we performed intracerebral injection of the same AAV vector
      (total dose of 3.8 x 10(11) or 1.9 x 10(12) vector genome, three sites of
      injection in the right hemisphere, two deposits per site of injection) into three
      selected areas of the centrum semiovale white matter, or in the deep gray matter
      nuclei (caudate nucleus, putamen, thalamus) of six non-human primates to evaluate
      vector distribution, as well as expression and activity of human ARSA. The
      procedure was perfectly tolerated, without any adverse effect or change in
      neurobehavioral examination. AAV vector was detected in a brain volume of 12-15
      cm(3) that corresponded to 37-46% of the injected hemisphere. ARSA enzyme was
      expressed in multiple interconnected brain areas over a distance of 22-33 mm.
      ARSA activity was increased by 12-38% in a brain volume that corresponded to 50
      65% of injected hemisphere. These data provide substantial evidence for potential
      benefits of brain gene therapy in patients with MLD.

PMID- 19837701
TI  - The pragmatic use of apomorphine at the end of life.
AB  - Parkinson's Disease (PD) is an irreversible degenerative neurological disorder
      with no known cure. Apomorphine is a potent short-acting D1/D2 dopamine agonist
      administered sub-cutaneously that is used in the treatment of PD. Optimising PD
      medication is an important aspect of end of life care. There are no previously
      reported cases of apomorphine providing symptom relief in terminal care of PD
      patients. This case highlights its potential benefits for symptom control at the
      end of life.

PMID- 19837700
TI  - The effect of food intake on gene expression in human peripheral blood.
AB  - Human gene expression traits have been shown to be dependent on gender, age and
      time of day in blood and other tissues. However, other factors that may impact
      gene expression have not been systematically explored. For example, in studies
      linking blood gene expression to obesity related traits, whether the fasted or
      fed state will be the most informative is an open question. Here, we employed a
      two-arm cross-over design to perform a genome-wide survey of gene expression in
      human peripheral blood to address explicitly this type of question. We were able
      to distinguish expression changes due to individual and time-specific effects
      from those due to food intake. We demonstrate that the transcriptional response
      to food intake is robust by constructing a classifier from the gene expression
      traits with >90% accuracy classifying individuals as being in the fasted or fed
      state. Gene expression traits that were best able to discriminate the fasted and
      fed states were more heritable and achieved greater coherence with respect to
      pathways associated with metabolic traits. The connectivity structure among gene
      expression traits was explored in the context of coexpression networks. Changes
      in the connectivity structure were observed between the fasted and fed states. We
      demonstrate that differential expression and differential connectivity are two
      complementary ways to characterize changes between fasted and fed states. Both
      gene sets were significantly enriched for genes associated with obesity related
      traits. Our results suggest that the pair of fasted/fed blood expression profiles
      provide more comprehensive information about an individual's metabolic states.

PMID- 19837702
TI  - Costs associated with resource utilization during the palliative phase of care: a
      Canadian perspective.
AB  - OBJECTIVE: This study aimed to evaluate prospectively the resource utilization
      and related costs during the palliative phase of care in five regions across
      Canada. SUBJECTS: A cohort of 248 patients registered in a palliative care
      program and their main informal caregivers were consecutively recruited. RESEARCH
      DESIGN: A prospective research design with repeated measures was adopted.
      Interviews were conducted at two-week intervals until the patient s passing or up
      to a maximum of 6 months. MEASURES: The survey questions prompted participants to
      provide information on the types and number of goods and services they used, and
      who paid for these goods and services. RESULTS: The largest cost component for
      study participants was inpatient hospital care stays, followed by home care and
      informal caregiving time. In regard to cost sharing, the public health care
      system (PHCS), the family, and not-for-profit organizations (NFPO) sustained
      respectively 71.3%, 26.6%, and 1.6% of the mean total cost per patient.
      CONCLUSION: Such results provide a comprehensive picture of costs related to
      palliative care in Canada, by specifying the cost sharing between the PHCS, the
      family, and NFPO.

PMID- 19837703
TI  - What progress has been made towards implementing national guidance on end of life
      care? A national survey of UK general practices.
AB  - The objectives of this study were to establish the extent to which UK primary
      care has adopted recommended practices on supportive and palliative care of
      adults with cancer, and to relate this to participation in national initiatives.
      We conducted a cross-sectional postal questionnaire survey of a random sample of
      UK general practices. In total, 60.0% of practices (2096 of 3495) responded to
      the survey: 61.5% reported involvement with the Gold Standards Framework (GSF);
      24.4% with the Liverpool or other End of Life Care Pathway; 12.3%, with the
      Preferred Place of Care (PPC) initiative; and 8.4% with Advance Care Planning
      (ACP). Participation in GSF contributed most to the variance in practice
      organization scores; and practice organization scores contributed most to the
      variance in clinical care scores. Participation in ACP or PPC, and higher
      clinical care scores were associated with an increased likelihood of reported
      high rates of death at home for cancer patients. Our findings appear to support
      the role of national initiatives in improving the quality of end-of-life care
      delivery in general practice. A population-based study would be required to
      assess the effect of end of life care on clinical outcomes and patient or carer
      experience.

PMID- 19837704
TI  - Recycling of wood for particle board production: accounting of greenhouse gases
      and global warming contributions.
AB  - The greenhouse gas (GHG) emissions related to the recycling of wood waste have
      been assessed with the purpose to provide useful data that can be used in
      accounting of greenhouse gas emissions. Here we present data related to the
      activities in a material recovery facility (MRF) where wood waste is shredded and
      foreign objects are removed in order to produce wood chips for use in the
      production of particleboard. The data are presented in accordance with the UOD
      (upstream, operational, downstream) framework presented in Gentil et al. (Waste
      Management & Research, 27, 2009). The GHG accounting shows that the emissions
      related to upstream activities (5 to 41 kg CO(2)-equivalents tonne( -1) wood
      waste) and to activities at the MRF (approximately 5 kg CO(2)-equivalents tonne(
      1) wood waste) are negligible compared to the downstream processing (-560 to -120
      kg CO(2)equivalents tonne(-1) wood waste). The magnitude of the savings in GHG
      emissions downstream are mainly related to savings in energy consumption for
      drying of fresh wood for particleboard production. However, the GHG account
      highly depends on the choices made in the modelling of the downstream system. The
      inclusion of saved electricity from avoided chipping of virgin wood does not
      change the results radically (-665 to -125 kg CO(2)-equivalents tonne(- 1) wood
      waste). However, if in addition it is assumed that the GHG emissions from
      combustion of wood has no global warming potential (GWP) and that the energy
      produced from excess wood due to recycling substitutes energy from fossil fuels,
      here assumed to be coal, potentially large downstream GHG emissions savings can
      be achieved by recycling of waste wood (-1.9 to -1.3 tonnes CO(2)-equivalents
      tonne(- 1) wood waste). As the data ranges are broad, it is necessary to
      carefully evaluate the feasibility of the data in the specific system which the
      GHG accounting is to be applied to.

PMID- 19837705
TI  - Efficiency of energy recovery from municipal solid waste and the resultant effect
      on the greenhouse gas balance.
AB  - Global warming is a focus of political interest and life-cycle assessment of
      waste management systems reveals that energy recovery from municipal solid waste
      is a key issue. This paper demonstrates how the greenhouse gas effects of waste
      treatment processes can be described in a simplified manner by considering energy
      efficiency indicators. For evaluation to be consistent, it is necessary to use
      reasonable system boundaries and to take the generation of electricity and the
      use of heat into account. The new European R1 efficiency criterion will lead to
      the development and implementation of optimized processes/systems with increased
      energy efficiency which, in turn, will exert an influence on the greenhouse gas
      effects of waste management in Europe. Promising technologies are: the increase
      of steam parameters, reduction of in-plant energy consumption, and the combined
      use of heat and power. Plants in Brescia and Amsterdam are current examples of
      good performance with highly efficient electricity generation. Other examples of
      particularly high heat recovery rates are the energy-from-waste (EfW) plants in
      Malmo and Gothenburg. To achieve the full potential of greenhouse gas reduction
      in waste management, it is necessary to avoid landfilling combustible wastes, for
      example, by means of landfill taxes and by putting incentives in place for
      increasing the efficiency of EfW systems.

PMID- 19837706
TI  - Recycling of stone cutting sludge in formulations of bricks and terrazzo tiles.
AB  - This study examines the possibility for enhancing the use of stone cutting sludge
      waste in the production of building bricks and terrazzo tiles, which would reduce
      both the environmental impact and the production costs. Stone cutting wastes in
      the form of sludge is currently generated at several factories in Jordan. At the
      Samara factory, incorporation of the sludge in the batch formulations of bricks
      and terrazzo tiles was examined. The physicochemical and mineralogical
      characteristics of the sludge were analyzed to identify the major components.
      Results indicated that the sludge generated from stone cutting could be used in
      producing concrete bricks. Mixtures of aggregates with added amounts of sludge
      were used successfully to produce non-load bearing bricks. Sludge was also used
      to produce terrazzo tiles and the results indicate that the transverse strength,
      water absorption and tile measurements, for all the taken samples, comply with
      Jordanian standards. The transverse strength decreased while water absorption
      increased as the sludge ratio increased.

PMID- 19837707
TI  - Impact of food waste fraction in municipal solid waste on sorption of heavy
      metals.
AB  - The presence of organic materials plays an important role in the fate of heavy
      metals that are co-disposed together with municipal solid wastes. As a part of an
      on-going research project, which aims to find out the most effective attenuation
      mechanism of heavy metal removal in landfills, sorption batch experiments were
      performed to assess the sorption behaviour of iron, copper, nickel and zinc on
      synthetic solid wastes containing 76% (W1) and 45% (W2) food waste percentages
      and waste-to-solution ratios ranging from 1:4 to 1:16. The analysis of sorption
      data suggested that the data fit a Freundlich equilibrium isotherm. The time
      required for reaching equilibrium conditions varied for each metal investigated,
      but all generally reached equilibrium conditions within 7 h. For both solid waste
      compositions, metal sorption increased with increase in waste-to-solution ratio,
      with the order of metal removal percentages consistently found to be Zn > Ni > Cu
      > Fe. The results also show that a large fraction of the heavy metals could be
      attenuated by sorption on the solid waste. The removal percentages for Zn and Ni
      were slightly higher for W2, whereas the removal percentages for Fe and Cu were
      approximately equal for both waste types. Overall, this study demonstrates that
      sorption is a viable process that can mitigate the potential adverse impacts of
      landfill leachate.

PMID- 19837708
TI  - Studying municipal solid waste generation and composition in the urban areas of
      Bhutan.
AB  - Bhutan lacks the solid waste data which are essential parameters for planning and
      scheduling of municipal solid waste management (MSWM) systems. The first ever
      large-scale research survey on solid waste generation and characterization in the
      urban areas of Bhutan was conducted between November 2007 and January 2008 using
      the method of waste sampling at source. The MSW generation rates in the urban
      centres were 0.53 kg capita(-1) day(- 1), which consists predominantly of organic
      waste materials of up to 58% indicating a great opportunity for composting.
      Domestic waste from the households contributed the maximum (47%) component of the
      total MSW generated from the urban centres followed by wastes from the commercial
      establishments. Attempt to study the correlation between household monthly income
      and the waste per capita generation rates did not yield any conclusive result.

PMID- 19837709
TI  - Effect of cohesion and fill amplification on seismic stability of municipal solid
      waste landfills using limit equilibrium method.
AB  - Municipal solid waste (MSW) landfills in seismic zones are subjected to the
      seismic forces both in the horizontal and vertical directions. The stability of
      landfills against these seismic forces was evaluated by computing the factor of
      safety of landfills with different modes of failure among which failures of
      landfills due to translation are very common. Conventionally, the seismic
      stability of landfill is evaluated by using pseudo-static limit equilibrium
      method. In the present study, seismic stability of landfills is evaluated by both
      the conventional pseudo-static and modern pseudo-dynamic method. The pseudo
      dynamic method is superior as it takes into account the effect of duration and
      frequency of earthquake motion and corresponding body waves in addition to the
      variation of earthquake accelerations along depth and time. In the present study,
      the effects of cohesion and fill amplification on seismic stability of landfill
      are also taken into account. It was noticed that, neglecting cohesion of fill
      material as well as liner material, results in a lower factor of safety and,
      hence, a very conservative/uneconomic design. Also, fill amplification is found
      to reduce the factor of safety values computed only by using the pseudo-dynamic
      method, showing its advantage. Generalized expressions are developed for factor
      of safety and yield acceleration against translational failure, which can be used
      for evaluating the seismic stability of MSW landfills. Comparisons of results
      under static condition with existing, similar methodology show a very good
      agreement. However, the present study seems to provide unique results for the
      seismic case.

PMID- 19837710
TI  - Municipal solid waste management scenarios for Attica and their greenhouse gas
      emission impact.
AB  - Disposal of municipal solid waste in sanitary landfills is still the main waste
      management method in the Attica region, as in most regions of Greece.
      Nevertheless, diversion from landfilling is being promoted by regional plans, in
      which the perspectives of new waste treatment technologies are being evaluated.
      The present study aimed to assess the greenhouse gas (GHG) emissions impact of
      different municipal solid waste treatment technologies currently under assessment
      in the new regional plan for Attica. These technologies are mechanical-biological
      treatment, mass-burn incineration and mechanical treatment and have been assessed
      in the context of different scenarios. The present study utilized existing
      methodologies and emission factors for the quantification of GHG emissions from
      the waste management process and found that all technologies under assessment
      could provide GHG emission savings. However, the performance and ranking of these
      technologies is strongly dependent on the existence of end markets for the waste
      derived fuels produced by the mechanical-biological treatment processes. In the
      absence of these markets the disposal of these fuels would be necessary and thus
      significant GHG savings would be lost.

PMID- 19837711
TI  - Global warming factors modelled for 40 generic municipal waste management
      scenarios.
AB  - Global warming factors (kg CO(2)-eq.-tonne(-1) of waste) have been modelled for
      40 different municipal waste management scenarios involving a variety of
      recycling systems (paper, glass, plastic and organics) and residual waste
      management by landfilling, incineration or mechanical-biological waste treatment.
      For average European waste composition most waste management scenarios provided
      negative global warming factors and hence overall savings in greenhouse gas
      emissions: Scenarios with landfilling saved 0-400, scenarios with incineration
      saved 200-700, and scenarios with mechanical-biological treatment saved 200- 750
      kg CO(2)-eq. tonne(- 1) municipal waste depending on recycling scheme and energy
      recovery. Key parameters were the amount of paper recycled (it was assumed that
      wood made excessive by paper recycling substituted for fossil fuel), the
      crediting of the waste management system for the amount of energy recovered (hard
      coal-based energy was substituted), and binding of biogenic carbon in landfills.
      Most other processes were of less importance. Rational waste management can
      provide significant savings in society's emission of greenhouse gas depending on
      waste composition and efficient utilization of the energy recovered.

PMID- 19837712
TI  - Characterization of methicillin-resistant Staphylococcus aureus and methicillin
      resistant coagulase-negative Staphylococcus spp. isolated from US West Coast
      public marine beaches.
AB  - OBJECTIVES: The aim of this study was to isolate and characterize methicillin
      resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase
      negative Staphylococcus spp. (MRCoNS) from marine water and intertidal beach sand
      from public beaches in Washington State, USA. METHODS: Fifty-one staphylococci
      from Washington State beaches were characterized using antimicrobial
      susceptibility testing, carriage of acquired tetracycline and/or macrolide
      resistance genes, staphylococcal cassette chromosome mec (SCCmec) typing, the BBL
      Crystal Gram-Positive ID System and/or 16S rRNA sequencing, coagulase test and
      multilocus sequence typing (MLST) for MRSA. RESULTS: Five multidrug-resistant
      MRSA SCCmec type I, of which three were MLST type ST45, one ST59 and one a new
      MLST type, ST1405, plus one susceptible non-typeable (NT) MRSA ST30 were
      characterized. Thirty-three MRCoNS isolates, representing 21 strains from 9
      Staphylococcus spp., carried a range of SCCmec types [I (2), II (6), III (3), V
      (2), I/II (1) and NT (7)] and varied in their antibiotic susceptibility to other
      antibiotic classes and carriage of acquired tetracycline/macrolide resistance
      gene(s). MRSA and MRCoNS donors co-transferred tet(M) and erm(A) genes to an
      Enterococcus faecalis recipient at a frequency of 10(-8). CONCLUSIONS: This is
      the first report of MRSA and MRCoNS isolated from marine water and intertidal
      beach sand. The MLST types and antibiotic carriage of five MRSA isolates were
      similar to hospital MRSA isolates rather than US community-acquired MRSA
      isolates. Our results suggest that public marine beaches may be a reservoir for
      transmission of MRSA to beach visitors as well as an ecosystem for exchange of
      antibiotic resistance genes among staphylococci and related genera.

PMID- 19837713
TI  - Non-compliance with recommendations for the practice of antibiotic prophylaxis
      and risk of surgical site infection: results of a multilevel analysis from the
      INCISO Surveillance Network.
AB  - OBJECTIVES: The aim of this study was to determine which surgical antibiotic
      prophylaxis (SAP) practices alter surgical site infection (SSI) risk. METHODS:
      Data were collected during a 7 year surveillance period (2001-07) from volunteer
      surgery wards participating in the INCISO Surveillance Network in Northern
      France. Main SAP practices, i.e. antibiotic choice, timing of first dose and
      total SAP duration, were evaluated and compliance checked based on French
      recommendations. The study focused on selected procedures in digestive,
      orthopaedic, gynaecological and cardiovascular surgery, for which standard SAP is
      recommended. Multilevel logistic regression analysis (a two-level random effect
      model) was carried out to identify SAP-, patient- and procedure-specific factors
      associated with SSI. RESULTS: Of 8029 patients who underwent the selected
      surgeries, 91.3% received SAP and 2.5% developed SSI. Among those receiving SAP,
      83.3% received appropriate antibiotic agents and 76.6% had an optimal timing of
      administration. SAP duration was considered to be appropriate in 35.0%, too long
      (SAP unnecessarily prolonged) in 45.2% and too short (lack of intra-operative
      redosing when recommended) in 19.8%. In the multivariate analysis, a too-short
      SAP duration remained the only inappropriate practice associated with higher SSI
      risk (odds ratio = 1.8, 95% confidence interval: 1.14-2.81), after adjustment for
      surgery procedure group, the National Nosocomial Infections Surveillance System
      risk index, age and infection risk variability among hospitals. No significant
      relationships were observed between SSI and the other SAP parameters.
      CONCLUSIONS: A too-short SAP duration was the most important SAP malpractice
      associated with an increased risk of SSI. Information directed at practitioners
      should be reinforced based on standard recommendations.

PMID- 19837714
TI  - Antimicrobial efficacy of eucalyptus oil and 1,8-cineole alone and in combination
      with chlorhexidine digluconate against microorganisms grown in planktonic and
      biofilm cultures.
AB  - OBJECTIVES: Effective disinfection and antisepsis is pivotal in preventing
      infections within the healthcare setting. Chlorhexidine digluconate (CHG) is a
      widely used disinfectant/antiseptic possessing broad-spectrum antimicrobial
      activity; however, its penetration into bacterial biofilms and human skin is
      poor. The aim of this study was to investigate the antimicrobial efficacy of
      crude eucalyptus oil (EO) and its main component 1,8-cineole (a recognized
      permeation enhancer), alone and in combination with CHG, against a panel of
      clinically relevant microorganisms grown in planktonic and biofilm cultures.
      METHODS: MICs and minimum bactericidal/fungicidal concentrations were determined
      for each microorganism grown in suspension and biofilm using microbroth dilution
      and ATP bioluminescence, respectively. Chequerboard assays were used to determine
      synergistic, indifferent or antagonistic interactions between CHG and EO or 1,8
      cineole. RESULTS: Antimicrobial activity was demonstrated by CHG, EO and 1,8
      cineole; however, CHG was significantly more active against microorganisms in
      both planktonic and biofilm modes of growth (P < 0.05). Crude EO was
      significantly more efficacious against microorganisms grown in suspension
      compared with 1,8-cineole (P < 0.05). Synergistic activity was demonstrated
      between CHG and both EO and 1,8-cineole against suspensions of Staphylococcus
      aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli and Candida
      albicans, and biofilm cultures of MRSA and Pseudomonas aeruginosa. CONCLUSIONS:
      In conclusion, CHG may be combined with either crude EO or its major component
      1,8-cineole for enhanced, synergistic antimicrobial activity against a wide range
      of microorganisms in planktonic and biofilm modes of growth; however, the
      superior antimicrobial efficacy associated with crude EO alone, compared with 1,8
      cineole, favours its combination with CHG.

PMID- 19837715
TI  - In vitro effect of physiological concentrations of human albumin on the
      antibacterial activity of tigecycline.
AB  - OBJECTIVES: To determine C(max) tigecycline activity in the presence/absence of
      physiological concentrations of human albumin with free fraction concentrations
      as controls. METHODS: Killing curves (final inoculum: 1.0-5.0 x 10(7) cfu/mL)
      were performed with 0.88 mg/L final concentrations (serum C(max) after a 100 mg 1
      h infusion) in Mueller-Hinton broth supplemented with Ca(2+) and Mg(2+) (MH) and
      in MH with 4 g/dL human albumin. Controls were curves in MH with concentrations
      similar to the free fraction (fC(max) = 0.17 mg/L) calculated using protein
      binding. Activity was measured as log(10) initial inoculum reduction (log(10)
      initial inoculum-log(10) at 12 h/24 h). Target strains (tigecycline MIC/MBC;
      mg/L) were: methicillin-resistant Staphylococcus aureus heteroresistant to
      vancomycin (0.12/0.25); Enterococcus faecium (0.12/0.25); Escherichia coli
      producing extended-spectrum beta-lactamase (0.12/0.25); and Acinetobacter
      baumannii (0.25/1). RESULTS: At 24 h the fC(max) produced mean decreases of < or
      =0.1 cfu/mL for all strains, in contrast to the bactericidal activity (mean >3
      log(10) reduction) provided by C(max) concentrations in the presence or absence
      of albumin for E. coli and E. faecium, and an activity nearly bactericidal for S.
      aureus (mean approximately 2.8 log(10) reduction). In the case of the A.
      baumannii isolate the C(max) in the presence or absence of albumin produced a
      mean reduction of 2.56 log(10) cfu/mL at 12 h (time of one dosing interval), with
      a bacteriostatic profile when considering 24 h colony counts (similar counts at 0
      and 24 h). CONCLUSIONS: Correcting the total concentration for the reported
      literature binding values is unreliable since tigecycline antibacterial activity
      was greater than that suggested by the free fraction of the drug.

PMID- 19837716
TI  - Molecular characterization of group B streptococci with reduced penicillin
      susceptibility recurrently isolated from a sacral decubitus ulcer.

PMID- 19837717
TI  - High clonal diversity in erythromycin-resistant Streptococcus pneumoniae invasive
      isolates in Madrid, Spain (2000-07).
AB  - OBJECTIVES: Erythromycin resistance in Streptococcus pneumoniae is still
      increasing worldwide. All 78 erythromycin-resistant S. pneumoniae isolates
      collected from blood cultures in our hospital (2000-07) were studied and the
      population structure was analysed by using different mathematical diversity
      indexes. METHODS: Erythromycin resistance determinants were screened by PCR. The
      population structure, including multilocus sequence typing, was analysed by using
      quantitative clonal diversity (diversity ratio, Simpson, Selander-Levin and
      Shannon mathematical indexes). RESULTS: The leading resistance gene was erm(B)
      (74.3% of the isolates), followed by the erm(B) plus mef(A) combination (17.9%)
      and mef(A) alone (7.7%). The most frequent serotypes were 14 (18%), 19A (15.4%)
      and 6B (11.5%). A polyclonal structure was detected in resistant strains,
      including the Spain(9V)-3, Spain(6B)-2 and Denmark(14)-32 international clones.
      Both genetic diversity and genetic distribution were high, particularly among
      clones containing erm(B) and erm(B) plus mef(A) determinants. CONCLUSIONS: The
      resistance determinants erm(B) and the combination of erm(B) plus mef(A) were
      observed within multiple S. pneumoniae bacteraemic clones. The preservation of a
      polyclonal structure might provide a suitable background for further evolution of
      antibiotic resistance.

PMID- 19837718
TI  - NAViGaTOR: Network Analysis, Visualization and Graphing Toronto.
AB  - SUMMARY: NAViGaTOR is a powerful graphing application for the 2D and 3D
      visualization of biological networks. NAViGaTOR includes a rich suite of visual
      mark-up tools for manual and automated annotation, fast and scalable layout
      algorithms and OpenGL hardware acceleration to facilitate the visualization of
      large graphs. Publication-quality images can be rendered through SVG graphics
      export. NAViGaTOR supports community-developed data formats (PSI-XML, BioPax and
      GML), is platform-independent and is extensible through a plug-in architecture.
      AVAILABILITY: NAViGaTOR is freely available to the research community from
      http://ophid.utoronto.ca/navigator/. Installers and documentation are provided
      for 32- and 64-bit Windows, Mac, Linux and Unix. CONTACT: juris@ai.utoronto.ca
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 19837719
TI  - INTERSNP: genome-wide interaction analysis guided by a priori information.
AB  - SUMMARY: Genome-wide association studies (GWAS) have lead to the identification
      of hundreds of genomic regions associated with complex diseases. Nevertheless, a
      large fraction of their heritability remains unexplained. Interaction between
      genetic variants is one of several putative explanations for the 'case of missing
      heritability' and, therefore, a compelling next analysis step. However, genome
      wide interaction analysis (GWIA) of all pairs of SNPs from a standard marker
      panel is computationally unfeasible without massive parallelization. Furthermore,
      GWIA of all SNP triples is utopian. In order to overcome these computational
      constraints, we present a GWIA approach that selects combinations of SNPs for
      interaction analysis based on a priori information. Sources of information are
      statistical evidence (single marker association at a moderate level), genetic
      relevance (genomic location) and biologic relevance (SNP function class and
      pathway information). We introduce the software package INTERSNP that implements
      a logistic regression framework as well as log-linear models for joint analysis
      of multiple SNPs. Automatic handling of SNP annotation and pathways from the KEGG
      database is provided. In addition, Monte Carlo simulations to judge genome-wide
      significance are implemented. We introduce various meaningful GWIA strategies
      that can be conducted using INTERSNP. Typical examples are, for instance, the
      analysis of all pairs of non-synonymous SNPs, or, the analysis of all
      combinations of three SNPs that lie in a common pathway and that are among the
      top 50,000 single-marker results. We demonstrate the feasibility of these and
      other GWIA strategies by application to a GWAS dataset and discuss promising
      results. AVAILABILITY: The software is available at http://intersnp.meb.uni
      bonn.de CONTACT: herold@imbie.meb.uni-bonn.de; becker@imbie.meb.uni-bonn.de.

PMID- 19837720
TI  - GeneE: gene and protein query expansion with disambiguation.
AB  - SUMMARY: When referring to genes, authors often use synonyms instead of the
      official gene symbols. In order to accurately retrieve as many relevant documents
      as possible, we have developed GeneE, a web application that expands a gene query
      to include all known synonyms, and adds disambiguation information for ambiguous
      terms, before forwarding the query to either PubMed, Google or Jane. The query
      expansion algorithm is also available as a web service. AVAILABILITY:
      http://biosemantics.org/geneE

PMID- 19837721
TI  - Liver X receptor in cholesterol metabolism.
AB  - The liver X receptors (LXRs) are nuclear receptors that are activated by
      endogenous oxysterols, oxidized derivatives of cholesterol. There are two
      isoforms of LXR, LXRalpha (NR1H3) and LXRbeta (NR1H2). Both LXRalpha and LXRbeta
      regulate gene expression by binding to DNA sequences associated with target genes
      as heterodimers with isoforms of the retinoid X receptor (RXR), RXRalpha (NR2B1),
      RXRbeta (NR2B2), and RXRgamma (NR2B3). LXRs act as cholesterol sensors: when
      cellular oxysterols accumulate as a result of increasing concentrations of
      cholesterol, LXR induces the transcription of genes that protect cells from
      cholesterol overload. In this review, we summarize the roles of LXRs in
      controlling cholesterol homeostasis, including their roles in bile acid synthesis
      and metabolism/excretion, reverse cholesterol transport, cholesterol biosynthesis
      and uptake, and cholesterol absorption/excretion in the intestine. The
      overlapping and distinct roles of the LXRalpha and LXRbeta isoforms, and the
      potential use of LXRs as attractive targets for treatment of cardiovascular
      disease are also discussed.

PMID- 19837722
TI  - Regulation of major histocompatibility complex gene expression in thyroid
      epithelial cells by methimazole and phenylmethimazole.
AB  - Increased expression of major histocompatibility complex (MHC) class-I genes and
      aberrant expression of MHC class-II genes in thyroid epithelial cells (TECs) are
      associated with autoimmune thyroid diseases. Previous studies have shown that
      methimazole (MMI) reduces MHC class-I expression and inhibits interferon-gamma
      (IFN-gamma or IFNG as listed in the MGI Database)-induced expression of the MHC
      class-II genes in TECs. The action of MMI on the MHC class-I genes is
      transcriptional, but its mechanism has not been investigated previously. In the
      present study, we show that in Fisher rat thyroid cell line 5 cells, the ability
      of MMI and its novel derivative phenylmethimazole (C10) to decrease MHC class-I
      promoter activity is similar to TSH/cAMP suppression of MHC class-I and TSH
      receptor genes, and involves a 39 bp silencer containing a cAMP response element
      (CRE)-like site. Furthermore, we show that C10 decreases MHC class-I gene
      expression to a greater extent than MMI and at 10- to 50-fold lower
      concentrations. C10 also reduces the IFN-gamma-induced increase in the expression
      of MHC class-I and MHC class-II genes more effectively than MMI. Finally, we show
      that in comparison to MMI, C10 is a better inhibitor of specific protein-DNA
      complexes that are formed with a CRE-like element on the MHC class-II promoter.
      These data support the conclusion that the immunosuppressive mechanism by which
      MMI and C10 inhibit MHC gene expression mimics 'normal' hormonal suppression by
      TSH/cAMP.

PMID- 19837723
TI  - Critical difference calculations revised: inclusion of variation in standard
      deviation with analyte concentration.
AB  - BACKGROUND: The critical difference (CD), the smallest difference between
      sequential laboratory results which is associated with a true change in the
      patient, is commonly calculated by assuming the same standard deviation (SD) for
      the initial and subsequent measurements. The calculation of the CD is re-examined
      without making this assumption. METHODS: A formula for CD is developed, which
      specifies that even with the assumption of constant coefficient of variations
      (CV) at the two measurement concentrations used in the calculation, there will be
      different SDs due to different concentrations. RESULTS: The effect of removing
      the assumption of constant SD is to increase the CD for rises in analyte
      concentration and to decrease the CD for falls in concentration. These effects
      are caused by increased SD for the second measurement compared with the first
      when the second measurement is higher, and the reverse when the second is lower.
      CONCLUSIONS: Replacing the usual assumption of similar total result SD for both
      measurements included in the CD calculation with a calculation of the SD at both
      analyte concentrations leads to an increase in the magnitude of the CD for rises
      in analyte concentration and a decrease for falls in analyte concentration. This
      change is proposed for all forms of CD calculations.

PMID- 19837724
TI  - Development of a method to measure plasma and whole blood choline by liquid
      chromatography tandem mass spectrometry.
AB  - BACKGROUND: Current gold standard markers for myocardial damage are troponins I
      and T, which are both sensitive and specific for the detection of myocardial
      infarction, but require up to 6 h to become reliably elevated in serum.
      Investigation into markers with potential to identify patients with early
      ischaemic changes is therefore intense. Choline is reported to be prognostic in
      patients presenting with acute coronary syndromes via its release from ischaemic
      cell membranes. METHODS: Liquid chromatography tandem mass spectrometry was used
      to develop a method to quantitate choline in plasma and blood. The method
      involves addition of a deuterated internal standard to an aliquot of plasma or
      blood followed by organic solvent addition, which precipitates the proteins in
      the sample. Preparation was carried out directly into a 96-deep-well plate.
      Chromatography of choline used a strong cation exchange column and separation
      used a Waters Atlantis dC18 analytical column positioned directly before the mass
      spectrometer source, allowing on-line preanalytical clean up of the sample.
      RESULTS: The lower limit of quantitation was 0.38 micromol/L, linearity was
      observed up to 754 micromol/L, with a working concentration range of 0.38-224
      micromol/L, inter- and intra-assay coefficients of variation were <6% and <4%,
      respectively. Samples were stable throughout five freeze-thaw cycles and recovery
      was between 94% and 114%. CONCLUSIONS: The assay was successfully validated in
      accordance with FDA guidelines and is suitable for quantitation of choline in
      research and clinical settings.

PMID- 19837725
TI  - Development of a high-resolution melting method for mutation detection in
      familial hypercholesterolaemia patients.
AB  - AIMS: Current screening methods, such as single strand conformational
      polymorphism (SSCP) and denaturing high performance liquid chromatography (dHPLC)
      that are used for detecting mutations in familial hypercholesterolaemia (FH)
      subjects are time consuming, costly and only 80-90% sensitive. Here we have
      tested high-resolution melt (HRM) analysis for mutation detection using the Rotor
      Gene(6000) realtime rotary analyser. Methods and subjects Polymerase chain
      reaction and melt conditions (HRM) for 23 fragments of the LDL-receptor gene, a
      region of exon 26 in the APOB gene (including p.R3527Q) and exon 7 of the PCSK9
      gene (including p.D374Y) were optimized. Two double stranded DNA saturating dyes,
      LC-Green and Syto9, were compared for sensitivity. Eighty-two samples with known
      mutations were used as positive controls. Twenty-eight Greek FH heterozygous
      patients and two homozygous patients from the UK and Croatia were screened.
      RESULTS: HRM was able to identify all the positive control mutations tested, with
      similar results with either dye. Eight different variations were found in 17 of
      the 28 Greek FH patients for an overall detection rate of 61%: c.41delT (1),
      p.W165X (1), p.C173R (3), p.S286R (2), p.V429M (4), p.G549D (4), p.V613I (1), and
      a previously unreported mutation p.F694V (1) which is predicted to be FH-causing
      by functional algorithms. Mutations were found in both the homozygous patients;
      p.Q92X (Croatia) and p.Y489C (UK); both patients were homozygous for their
      respective mutations. CONCLUSIONS: HRM is a sensitive, robust technique that
      could significantly reduce the time and cost of screening for mutations in a
      clinical setting.

PMID- 19837726
TI  - Comparison of focus HerpesSelect and Kalon HSV-2 gG2 ELISA serological assays to
      detect herpes simplex virus type 2 antibodies in a South African population.
AB  - INTRODUCTION: Sero-epidemiological studies of herpes simplex virus (HSV) type 2
      infection in Africa remain difficult to interpret as a result of the high rate of
      false-positive results observed when using the new recombinant gG2 HSV-2 ELISA
      tests. The performance of two widely used gG2 ELISA was compared to derive an
      appropriate testing algorithm for use in South Africa. METHODS: Sera from 210
      women attending family planning clinics in Johannesburg were tested using
      HerpeSelect and Kalon HSV-2 gG2 assays. Sera from 20 discordant pairs, 44
      concordant positive and 33 concordant negative samples were further tested by HSV
      Western blot. The sensitivity and specificity of each test and of combination
      algorithms compared with Western blot were calculated. RESULTS: HerpeSelect had a
      sensitivity of 98% (95% CI 95 to 100) and specificity of 61% (95% CI 48 to 74).
      Kalon was less sensitive (89%, 95% CI 83 to 94) but more specific (85%, 95% CI 61
      to 100). Seroprevalence may have been overestimated by as much as 14% by
      HerpeSelect. Specificity was improved by raising the cut-off index for the
      determination of a positive result for HerpeSelect (to >or=3.5), but not for
      Kalon. HIV-1 infection reduced the specificity of HerpeSelect to 30%. Improved
      sensitivity and specificity were obtained by a two-test algorithm using
      HerpeSelect (>or=3.5) as the first test and Kalon to resolve equivocal results
      (sensitivity 92%, 95% CI 82 to 98; specificity 91%, 95% CI 79 to 98). CONCLUSION:
      Newer HSV-2 serological tests have low specificity in this South African
      population with a high HIV-1 prevalence. Two-step testing strategies could
      provide rational testing alternatives to Western blot.

PMID- 19837727
TI  - Prevalence of unsafe sex with one's steady partner either HIV-negative or of
      unknown HIV status and associated determinants in Cameroon (EVAL ANRS12-116
      survey).
AB  - OBJECTIVE: Our study aimed at estimating the prevalence of inconsistent condom
      use and at identifying its determinants in steady partnerships among people
      living with HIV/AIDS (PLWHA) in Cameroon. METHODS: Analyses were based on data
      collected during the national cross-sectional multicentre survey EVAL (ANRS 12
      116), which was conducted in Cameroon between September 2006 and March 2007 among
      3151 adult PLWHA diagnosed HIV-positive for at least 3 months. The study
      population consisted of the 907 survey participants who reported sexual activity
      during the previous 3 months, with a steady partner either HIV-negative or of
      unknown HIV status. Logistic regression was used to identify factors associated
      with individuals' report of inconsistent condom use during the previous 3 months.
      RESULTS: Inconsistent condom use was reported by 35.3% of sexually active PLWHA.
      In a multivariate analysis adjusted for socio-demographic characteristics, not
      receiving antiretroviral therapy (OR (95% CI): 2.28 (1.64 to 3.18)) was
      independently associated with inconsistent condom use. CONCLUSIONS: The
      prevalence of unsafe sex remains high among sexually active PLWHA in Cameroon.
      Treatment with antiretroviral therapy is identified as a factor associated with
      safer sex, which further encourages the continuation of the national policy for
      increasing access to HIV treatment and care, and underlines the need to develop
      counselling strategies for all patients.

PMID- 19837728
TI  - Rapid decline in presentations of genital warts after the implementation of a
      national quadrivalent human papillomavirus vaccination programme for young women.
AB  - OBJECTIVE: This study aimed to determine if the Australian human papillomavirus
      (HPV) vaccination programme has had a population impact on presentations of
      genital warts. METHODS: Retrospective study comparing the proportion of new
      clients with genital warts attending Melbourne Sexual Health Centre (MSHC) from
      January 2004 to December 2008. Australia provided free quadrivalent HPV vaccine
      to 12-18-year-old girls in a school-based programme from April 2007, and to women
      26 years and younger through general practices from July 2007. RESULTS: 36,055
      new clients attended MSHC between 2004 and 2008 and genital warts were diagnosed
      in 3826 (10.6%; 95% CI 10.3 to 10.9). The proportion of women under 28 years with
      warts diagnosed decreased by 25.1% (95% CI 30.5% to 19.3%) per quarter in 2008.
      Comparing this to a negligible increase of 1.8% (95% CI 0.2% to 3.4%) per quarter
      from the start of 2004 to the end of 2007 also in women under 28 years generates
      strong evidence of a difference in these two trends (p<0.001). There was no
      evidence of a difference in trend for the quarterly proportions before and after
      the end of 2007 for any other subgroup, and on only one occasion was there strong
      evidence of a trend different to zero, for heterosexual men in 2008 in whom the
      average quarterly change was a decrease of 5% (95% CI 0.5% to 9.4%; p = 0.031).
      CONCLUSIONS: The data suggest that a rapid and marked reduction in the incidence
      of genital warts among vaccinated women may be achievable through an HPV
      vaccination programme targeting women, and supports some benefit being conferred
      to heterosexual men.

PMID- 19837729
TI  - Usefulness of routine lumbar puncture in non-HIV patients with latent syphilis of
      unknown duration.
AB  - OBJECTIVES: To evaluate the usefulness of routine lumbar puncture in non-HIV
      patients with untreated latent syphilis. METHODS: We conducted a prospective
      study in Seoul National University Bundang Hospital from May 2003 to December
      2005. Participants in routine health check-ups of the healthcare system were
      screened for serological evidence of syphilis by the Treponema pallidum particle
      agglutination (TPPA) test. Lumbar puncture was performed, with consent, on
      untreated latent syphilitic patients. Neurosyphilis was defined as positivity for
      cerebrospinal fluid Venereal Disease Research Laboratory (CSF VDRL) or
      pleocytosis with positivity for CSF TPPA or elevation of CSF protein with IgG
      index exceeding 0.85. RESULTS: Of 21 507 participants, 282 (1.4%) had serological
      evidence of syphilis. 117 (41%) of these had a history of syphilis treatment and
      2 were seropositive for HIV. Among the 163 non-HIV patients with untreated latent
      syphilis, 70 (43%) underwent lumbar puncture. All the patients had VDRL titres
      less than 1:16. Abnormal neurological signs or symptoms were present in eight
      (11%) patients. CSF abnormalities were seen in 57 (81%), but no patient (0%, 95%
      CI 0 to 6.2) was diagnosed with neurosyphilis. CONCLUSIONS: The estimated
      prevalence of neurosyphilis among non-HIV patients with untreated latent syphilis
      and serum VDRL <1:16, was below 6.2%.

PMID- 19837730
TI  - Characterisation of Chlamydia trachomatis by ompA sequencing and multilocus
      sequence typing in a Swedish county before and after identification of the new
      variant.
AB  - OBJECTIVES: In 2006 a new variant of Chlamydia trachomatis (nvCT), with a
      deletion in the cryptic plasmid, was reported in Sweden. This deletion included
      the targets for the genetic diagnostic systems used in many clinical laboratories
      and resulted in thousands of false-negative results. The aim of this study was to
      characterise consecutive Chlamydia tissue culture-positive samples from 2006 in
      Orebro County, after identification of the nvCT, and to compare the results from
      samples collected in the same county in 1999-2000. The study also aimed to
      evaluate the discriminatory capacity of multilocus sequence typing (MLST)
      compared with ompA sequencing. METHODS: ompA sequencing and MLST was used to
      characterise 100 consecutive Chlamydia tissue culture-positive samples. RESULTS:
      A significant (p<0.001) increase of genotype E, from 47% in 1999-2000 to 69% in
      2006, was detected. All 41 nvCT isolates from 2006 displayed an identical ompA
      genotype E and MLST profile. Excluding the nvCT isolates, the distribution of
      ompA genotypes is similar to the genotyping results from 1999-2000. Among the
      wild-type genotype E isolates from 2006, 14 unique MLST sequence types were
      obtained from 26 isolates while they were identical in ompA genotyping. The
      discriminatory power (D) of C trachomatis strains in this material was 83.5%
      using the MLST system compared with 49.5% utilising ompA sequencing. CONCLUSION:
      In all, MLST enables improved studies of the molecular epidemiology of C
      trachomatis. All nvCT isolates from 2006 displayed an identical ompA genotype E
      and MLST profile, which strongly indicates a clonal spread of the nvCT.

PMID- 19837732
TI  - Fervidicoccus fontis gen. nov., sp. nov., an anaerobic, thermophilic
      crenarchaeote from terrestrial hot springs, and proposal of Fervidicoccaceae fam.
      nov. and Fervidicoccales ord. nov.
AB  - Two novel thermophilic and slightly acidophilic strains, Kam940(T) and Kam1507b,
      which shared 99 % 16S rRNA gene sequence identity, were isolated from terrestrial
      hot springs of the Uzon caldera on the Kamchatka peninsula. Cells of both strains
      were non-motile, regular cocci. Growth was observed between 55 and 85 degrees C,
      with an optimum at 65-70 degrees C (doubling time, 6.1 h), and at pH 4.5-7.5,
      with optimum growth at pH 5.5-6.0. The isolates were strictly anaerobic
      organotrophs and grew on a narrow spectrum of energy-rich substrates, such as
      beef extract, gelatin, peptone, pyruvate, sucrose and yeast extract, with yields
      above 10(7) cells ml(-1). Sulfate, sulfite, thiosulfate and nitrate added as
      potential electron acceptors did not stimulate growth when tested with peptone.
      H(2) at 100 % in the gas phase inhibited growth on peptone. Glycerol dibiphytanyl
      glycerol tetraethers (GDGTs) with zero to four cyclopentyl rings were present in
      the lipid fraction of isolate Kam940(T). The G+C content of the genomic DNA of
      strain Kam940(T) was 37 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that the isolates were archaea of the phylum Crenarchaeota,
      only distantly related to the cultured members of the class Thermoprotei (no more
      than 89 % identity), and formed an independent lineage adjacent to the orders
      Desulfurococcales and Acidilobales and clustering only with uncultured clones
      from hot springs of Yellowstone National Park and Iceland as the closest
      relatives. On the basis of their phylogenetic position and novel phenotypic
      features, isolates Kam940(T) and Kam1507b are proposed to be assigned to a new
      genus and species, Fervidicoccus fontis gen. nov., sp. nov. The type strain of
      Fervidicoccus fontis is strain Kam940(T) (=DSM 19380(T) =VKM B-2539(T)). The
      phylogenetic data as well as phenotypic properties suggest that the novel
      crenarchaeotes form the basis of a new family, Fervidicoccaceae fam. nov., and
      order, Fervidicoccales ord. nov., within the class Thermoprotei.

PMID- 19837731
TI  - Gene expression analysis in cadmium-stressed roots of a low cadmium-accumulating
      solanaceous plant, Solanum torvum.
AB  - Solanum torvum Sw. cv. Torubamubiga (TB) is a low cadmium (Cd)-accumulating
      plant. To elucidate the molecular mechanisms of the Cd acclimation process in TB
      roots, transcriptional regulation was analysed in response to mild Cd treatment:
      0.1 muM CdCl(2) in hydroponic solution. A unigene set consisting of 6296 unigene
      sequences was constructed from 18 816 TB cDNAs. The distribution of functional
      categories was similar to tomato, while 330 unigenes were suggested to be TB
      specific. For expression profiling, the SuperSAGE method was adapted for use with
      Illumina sequencing technology. Expression tag libraries were constructed from Cd
      treated (for 3 h, 1 d, and 3 d) and untreated roots, and 34 269 species of
      independent tags were collected. Moreover, 6237 tags were ascribed to the TB or
      eggplant (aubergine) unigene sequences. Time-course changes were examined, and
      2049 up- and 2022 down-regulated tags were identified. Although no tags annotated
      to metal transporter genes were significantly regulated, a tag annotated to
      AtFRD3, a xylem-loading citrate transporter, was down-regulated. In addition to
      induction of heavy metal chaperone proteins, antioxidative and sulphur
      assimilating enzymes were induced, confirming that oxidative stress developed
      even using a mild Cd concentration. Rapid repression of dehydration-related
      transcription factors and aquaporin isoforms suggests that dehydration stress is
      a potential constituent of Cd-induced biochemical impediments. These
      transcriptional changes were also confirmed by real-time reverse transcription
      PCR. Further additions of TB unigene sequences and functional analysis of the
      regulated tags will reveal the molecular basis of the Cd acclimation process,
      including the low Cd-accumulating characteristics of TB.

PMID- 19837733
TI  - Pseudidiomarina aestuarii sp. nov., a marine bacterium isolated from shallow
      coastal seawater.
AB  - A non-motile, rod-shaped and aerobic marine bacterium, designated strain
      KYW314(T), was isolated from seawater collected from the South Sea, Republic of
      Korea. Cells were Gram-negative, catalase- and oxidase-positive and had
      proteolytic activity. The major fatty acids were iso-C(15 : 0) (17.2 %), C(16 :
      0) (11.1 %), iso-C(17 : 0) (10.5 %) and C(18 : 1)omega 7c (10.0 %). The DNA G+C
      content was 56.4 mol%. A phylogenetic tree based on 16S rRNA gene sequences
      showed that strain KYW314(T) formed a lineage within the genus Pseudidiomarina
      (95.4-97.3 % sequence similarity) and a distinct branch within the clade
      containing Pseudidiomarina taiwanensis PIT1(T) and Pseudidiomarina sediminum
      c121(T). Phenotypic characteristics could distinguish strain KYW314(T) from
      members of the genus Pseudidiomarina. On the basis of the data presented, strain
      KYW314(T) represents a novel species, for which the name Pseudidiomarina
      aestuarii sp. nov. is proposed. The type strain is KYW314(T) (=KCTC 22740(T) =JCM
      16344(T)).

PMID- 19837734
TI  - Lachancea nothofagi sp. nov., a yeast associated with Nothofagus species in
      Patagonia, Argentina.
AB  - Six strains of a novel yeast species were isolated from Nothofagus species trees
      in native forests in Patagonia, Argentina. The strains were isolated from bark,
      fluxes and the ectomycorrhizospheric soil fraction of Nothofagus antarctica,
      Nothofagus nervosa and Nothofagus pumilio. Analysis of the D1/D2 large-subunit
      rDNA sequences indicated that the novel species belonged to the genus Lachancea
      and is closely related to Lachancea meyersii. The name Lachancea nothofagi sp.
      nov. is proposed to accommodate these strains. The type strain is UWOPS 99
      807.3(T) (=CBS 11611(T)=NRRL Y-48670(T)).

PMID- 19837735
TI  - Planotetraspora kaengkrachanensis sp. nov. and Planotetraspora phitsanulokensis
      sp. nov., isolated from soil.
AB  - Two novel bacterial strains were isolated from tropical rain forest soil from
      Thailand. Strains A-T 0875(T) and A-T 1383(T) stained Gram-positive and were
      filamentous bacteria that developed cylindrical sporangia containing four oval-
      to rod-shaped spores at the ends of short sporangiophores on branched aerial
      mycelium. The cell-wall peptidoglycan contained meso-diaminopimelic acid,
      glutamic acid and alanine as cell-wall amino acids; whole-cell hydrolysates
      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-methyl-C(17 : 0). For
      both strains, the G+C content of the genomic DNA was 71 mol%. Phenotypic and
      chemotaxonomic analyses showed that the characteristics of the two isolates were
      typical of members of the genus Planotetraspora. Furthermore, 16S rRNA gene
      sequence analysis also indicated that the strains belonged to the genus
      Planotetraspora but as representatives of two novel species. Following an
      evaluation of our phenotypic, chemotaxonomic and genotypic studies, two novel
      species are proposed, Planotetraspora kaengkrachanensis sp. nov. (type strain A-T
      0875(T)=BCC 24832(T)=NBRC 104272(T)) and Planotetraspora phitsanulokensis sp.
      nov. (type strain A-T 1383(T)=BCC 26045(T)=NBRC 104273(T)).

PMID- 19837740
TI  - Supermarket chains warn that minimum pricing of alcohol will not stop binge
      drinking.

PMID- 19837742
TI  - Rehabilitation in patients admitted to intensive care.

PMID- 19837741
TI  - The PRaCTICaL study of nurse led, intensive care follow-up programmes for
      improving long term outcomes from critical illness: a pragmatic randomised
      controlled trial.
AB  - OBJECTIVES: To test the hypothesis that nurse led follow-up programmes are
      effective and cost effective in improving quality of life after discharge from
      intensive care. DESIGN: A pragmatic, non-blinded, multicentre, randomised
      controlled trial. SETTING: Three UK hospitals (two teaching hospitals and one
      district general hospital). PARTICIPANTS: 286 patients aged >or=18 years were
      recruited after discharge from intensive care between September 2006 and October
      2007. INTERVENTION: Nurse led intensive care follow-up programmes versus standard
      care. Main outcome measure(s) Health related quality of life (measured with the
      SF-36 questionnaire) at 12 months after randomisation. A cost effectiveness
      analysis was also performed. RESULTS: 286 patients were recruited and 192
      completed one year follow-up. At 12 months, there was no evidence of a difference
      in the SF-36 physical component score (mean 42.0 (SD 10.6) v 40.8 (SD 11.9),
      effect size 1.1 (95% CI -1.9 to 4.2), P=0.46) or the SF-36 mental component score
      (effect size 0.4 (-3.0 to 3.7), P=0.83). There were no statistically significant
      differences in secondary outcomes or subgroup analyses. Follow-up programmes were
      significantly more costly than standard care and are unlikely to be considered
      cost effective. CONCLUSIONS: A nurse led intensive care follow-up programme
      showed no evidence of being effective or cost effective in improving patients'
      quality of life in the year after discharge from intensive care. Further work
      should focus on the roles of early physical rehabilitation, delirium, cognitive
      dysfunction, and relatives in recovery from critical illness. Intensive care
      units should review their follow-up programmes in light of these results. TRIAL
      REGISTRATION: ISRCTN 24294750.

PMID- 19837743
TI  - Applying for ethical approval for research in the United Kingdom.

PMID- 19837744
TI  - Panton-Valentine leucocidin associated Staphylococcus aureus infections.

PMID- 19837746
TI  - Glass fibre reinforced versus multistranded bonded orthodontic retainers: a 2
      year prospective multi-centre study.
AB  - The objective of this study was to compare glass fibre reinforced (GFR) with
      multistranded bonded orthodontic retainers in terms of success rate and
      periodontal implications. A 2 year parallel study was conducted of 184 patients
      scheduled to receive bonded retainers in the upper and lower anterior segments.
      In three centres, the patients (mean age 14 years; 90 males and 94 females) were
      sequentially assigned to receive GFR retainers containing 500 unidirectional
      glass fibres (GFR500), 1000 unidirectional glass fibres (GFR1000), or
      multistranded retainers (gold standard). Retainer failures and periodontal
      conditions were monitored every 6 months. In a control group of 90 subjects
      without retainers, periodontal conditions were examined (negative control). Of
      the 274 recruited patients, 15 dropped out during the 2 year study period. Kaplan
      Meier plots were drawn to assess survival of the different retainers. The Mantel
      Cox log-rank test was used to identify significant differences in survival
      functions among the groups. Repeated measures analysis of variance and
      appropriate post hoc tests were adopted to evaluate periodontal conditions over
      time. GFR retainers showed unacceptably high failure rates in comparison with
      multistranded retainers (51 versus 12 per cent). The most significant periodontal
      conditions were found in patients with GFR retainers with no significant
      differences between the GFR500 and the GFR1000 group for any parameter at any
      time point. Subjects without retainers showed significantly lower levels of
      gingival inflammation and plaque accumulation when compared with patients in any
      retainer group. Multistranded retainers should remain the gold standard for
      orthodontic retention, although periodontal complications are common. The use of
      GFR retainers should be discouraged in daily practice.

PMID- 19837747
TI  - Prevalence of hypodontia in orthodontic patients in Brasilia, Brazil.
AB  - The purpose of this retrospective study was to determine the prevalence of
      hypodontia and associated dental anomalies in patients undergoing orthodontic
      treatment in Brasilia, Brazil, over a 2 year period (1998-2000). The records of
      1049 orthodontic patients between 10 and 15.7 years of age (507 males and 542
      females) from 16 orthodontic clinics were analysed. Descriptive statistics were
      performed for the study variables. A chi-square test was used to determine the
      difference in the prevalence of hypodontia between genders. The prevalence of
      hypodontia was 6.3 per cent (39.4 per cent males and 60.6 per cent females) with
      no statistically significant difference between the genders. One case of
      oligodontia was observed. The maxillary lateral incisor was the most frequently
      missing tooth, followed by the mandibular second premolar. All cases of
      hypodontia, except one, were associated with at least one other dental anomaly.
      These associated dental anomalies were retained primary teeth (30.3 per cent),
      ectopic canine eruption (25.8 per cent), taurodontism (21.2 per cent), and peg
      shaped maxillary lateral incisors (16.7 per cent).

PMID- 19837748
TI  - Synthesis and biologic study of IV-14, a new ribonucleoside radiotracer for tumor
      visualization.
AB  - Uridine-cytidine kinase (UCK) 2, an enzyme normally expressed in human placenta
      and testis and highly overexpressed in many neoplasias of blood and solid
      tissues, catalyzes monophosphorylation of pyrimidine ribonucleosides with
      efficiency 15- to 20-fold higher than that of ubiquitously expressed isozyme
      UCK1. In this paper, we report the synthesis of 3'-(E)-(2-iodovinyl)uridine (IV
      14) and its preclinical evaluation as a new radiotracer derived from a UCK2
      selective antitumor agent, 3'-(ethynyl)uridine. METHODS: Radioiodinated IV-14 was
      prepared from the respective stannyl precursor. (131)I-IV-14 was studied in
      cellular uptake assays and tested for stability in serum as well as for stability
      to thymidine phosphorylase, liver-, and mucosa-specific murine uridine
      phosphorylases. UCK1 and UCK2 expression levels in different tumor cell lines
      were determined by Western blot. Cellular distribution of (131)I-IV-14 was
      determined in HL60 cells. Biodistribution studies and gamma-camera scintigraphy
      were performed on an HL60-xenografted severe combined immunodeficiency (SCID)
      mouse model. RESULTS: (131)I-IV-14 demonstrated excellent stability in serum. It
      was stable to human thymidine phosphorylase and to liver- and mucosa-specific
      murine uridine phosphorylases. Cellular uptake after 24 h of incubation with
      (131)I-IV-14 was 4.27 +/- 0.21, 3.66 +/- 0.13, 2.69 +/- 0.07, 2.24 +/- 0.18, and
      3.26 +/- 0.18 percentage injected dose per 5 x 10(5) Mia-PaCa-2, CX-1, HL60,
      Capan-1, and Panc-1 cells, respectively. Uptake and retention of IV-14 were
      regulated by 2 factors: UCK2 expression level and intracellular transport
      mediated partially via human equilibrating nucleoside transporter 1. A
      biodistribution study of (131)I-IV-14 in an HL60-xenografted SCID mouse model
      showed that at 4 h after injection the greatest amount of retained radioactivity
      was in tumor. The tissue-to-tumor ratio 4 h after injection was 1.0 +/- 0.24 for
      tumor, 0.40 +/- 0.18 for spleen, 0.25 +/- 0.12 for colon, 0.14 +/- 0.07 for small
      intestine, and less than 0.1 for other sites. Scintigraphy with (123)I-IV-14 4 h
      after injection showed the tumor well. In addition, high accumulation of
      radioiodide in the stomach content was observed and was presumably due to
      metabolic degradation of IV-14. CONCLUSION: IV-14 is a UCK2-specific marker,
      allowing for in vivo addressing of tumors with high RNA synthesis independent of
      proliferation rate.

PMID- 19837749
TI  - PET of malignant melanoma using 18F-labeled metallopeptides.
AB  - Melanocortin type 1 receptor (MC1R), also known as alpha-melanocyte-stimulating
      hormone (alpha-MSH) receptor, is an attractive molecular target for melanoma
      imaging and therapy. An (18)F-labeled linear alpha-MSH peptide ((18)F-FB-Ac-Nle
      Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH(2) [NAPamide]) shows promising melanoma imaging
      properties but with only moderate tumor uptake and retention. A transition metal
      rhenium-cyclized alpha-MSH peptide, ReO[Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3
      13) (ReCCMSH(Arg(11))), has shown high in vitro binding affinity to MC1R and
      excellent in vivo melanoma-targeting profiles when labeled with radiometals.
      Therefore, we hypothesized that ReCCMSH(Arg(11)) could be a good platform for the
      further development of an (18)F-labeled probe for PET of MC1R-positive malignant
      melanoma. METHODS: In this study, the metallopeptide Ac-d-Lys-ReCCMSH(Arg(11))
      was synthesized using conventional solid-phase peptide synthesis chemistry and a
      rhenium cyclization reaction. The resulting peptides were then labeled with N
      succinimidyl-4-(18)F-fluorobenzoate ((18)F-SFB). The (18)F-labeled
      metallopeptides were further tested for their in vitro receptor binding
      affinities, in vivo biodistribution, and PET imaging properties. RESULTS: Both
      isomers of Ac-d-Lys-ReCCMSH(Arg(11)), named as RMSH-1 and RMSH-2, were purified
      and identified by high-performance liquid chromatography. The binding affinities
      of RMSH-1 and RMSH-2 and their respective (19)F-SFB-conjugated peptides ((19)F-FB
      RMSH-1 and (19)F-FB-RMSH-2) were all determined to be within nanomolar range.
      Both (18)F-labeled metallopeptides showed good tumor uptake in the B16F10 murine
      model, with high MC1R expression, but much lower uptake in the A375M human
      melanoma xenografted in mice, indicating low MC1R expression. (18)F-FB-RMSH-1,
      when compared with (18)F-FB-RMSH-2, displayed more favorable in vivo performance
      in terms of slightly higher tumor uptakes and much lower accumulations in the
      kidney and liver at 2 h after injection. Small-animal PET of (18)F-FB-RMSH-1 and 
      2 in mice bearing B16F10 tumors at 1 and 2 h showed good tumor imaging quality.
      As expected, much lower tumor uptakes and poorer tumor-to-normal organ contrasts
      were observed for the A375M model than for the B16F10 model. (18)F-FB-RMSH-1 and 
      2 showed higher tumor uptake and better tumor retention than did (18)F-FB
      NAPamide. CONCLUSION: Specific in vivo targeting of (18)F-FB-RMSH-1 to malignant
      melanoma was successfully achieved in preclinical models with high MC1R
      expression. Thus, the radiofluorinated metallopeptide (18)F-FB-RMSH-1 is a
      promising molecular probe for PET of MC1R-positive tumors.

PMID- 19837750
TI  - Chemotherapy response monitoring of colorectal liver metastases by dynamic Gd
      DTPA-enhanced MRI perfusion parameters and 18F-FDG PET metabolic rate.
AB  - In this study, we examined the in vivo relationship between functional tumor
      vasculature, determined by dynamic contrast-enhanced (DCE-) MRI, and tumor
      metabolism, determined by dynamic (18)F-FDG PET, during cytotoxic treatment of
      patients with colorectal liver metastases. METHODS: Twenty-three patients
      underwent DCE-MRI (using gadolinium dimeglumine) and dynamic (18)F-FDG PET at
      baseline and after 3 treatment cycles, unless treatment was terminated because of
      toxicity. Parameters for vasculature (rate constant between extravascular
      extracellular space and blood plasma [k(ep)] and volume transfer constant
      [K(trans)]), extracellular space (v(e)), tumor size (the maximal axial diameter
      of each included lesion [MAD]), and metabolism (glucose metabolic rates
      [MR(glc)]) were derived, and changes during treatment were correlated. Overall
      survival (OS) and progression-free survival (PFS) served as outcome measures for
      the predictive abilities of pretreatment parameters and of treatment-related
      parameter changes. RESULTS: Pretreatment MR(glc) and MAD were individually
      predictive for OS and PFS. During treatment, K(trans) increased significantly,
      but this increase could not be confirmed in a lesion-by-lesion analysis. MR(glc)
      decreased significantly (P < 0.001). No correlations were found for changes in
      DCE-MRI parameters and DeltaMR(glc). No relationship was found between changes in
      DCE-MRI parameters and OS or PFS. DeltaMR(glc) was able to predict OS (P = 0.008)
      after correction for confounders. CONCLUSION: The efficacy of cytotoxic
      chemotherapy assessed by reduction in tumor metabolism does not depend on
      pretreatment properties of the tumor vasculature determined by DCE-MRI. Cytotoxic
      chemotherapy does not alter DCE-MRI-derived properties of tumor vasculature but
      decreases glucose consumption of tumor cells.

PMID- 19837751
TI  - The advantages of nanoparticles for PET.
AB  - Nanoparticles have an advantage for molecular imaging in that many
      functionalities can be added to the surface and interior of the particle. This
      brief review focuses on the design of nanomaterials that take advantage of PET.
      An evolutionary approach is presented, leading to the optimization of the
      nanoparticle composition and structure to achieve controlled in vivo circulation
      and tissue-selective targeting. Organic and inorganic nanostructures are
      included. Nanoprobes for PET of angiogenesis and cancer are highlighted.

PMID- 19837752
TI  - Quantitative radionuclide studies of bone.

PMID- 19837754
TI  - Using dual-tracer PET to predict the biologic behavior of human colorectal
      cancer.
AB  - (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) have been proven
      useful in diagnosing and staging many types of cancer but with emphasis on
      different aspects of tumor biology. The aim of the current study was to evaluate
      whether (18)F-FDG and (18)F-FLT can be used complementarily in monitoring the
      biologic characteristics of colorectal cancer (CRC). METHODS: Human CRC cell
      lines SW480 and SW620 of the same genetic origin but different metastatic
      potential were cultured and implanted into nude mice to create CRC models. Uptake
      of (18)F-FDG and (18)F-FLT in SW480 and SW620 cells in vitro was assessed after
      incubation with radiotracers for 0, 30, 60, 90, and 120 min. In vivo imaging of
      SW480 and SW620 tumor-bearing mice was performed using small-animal PET/CT at 60
      min after injection of each tracer. A region of interest was drawn over tumor and
      background to calculate the tumor-to-nontumor ratio (T/NT) using software on
      reconstructed images. Tumor growth rate, metastatic status, and survival time
      were assessed in tumor-bearing mice. The relationship between uptake of the
      tracers, metastatic capability, and tumor marker expression was evaluated using
      linear regression. RESULTS: SW480 tumors grew more quickly than SW620 tumors (t =
      3.332, P = 0.004). A higher incidence of lung and liver metastases was noted for
      SW480 than for SW620 (P = 0.023). Uptake in SW480 and SW620 cells was
      significantly different between (18)F-FDG and (18)F-FLT (t = 2.507, P = 0.021,
      vs. t = 3.497, P = 0.002). In the small-animal PET study, the T/NT of (18)F-FDG
      did not differ between SW480 and SW620 tumors (2.69 +/- 0.98 vs. 3.09 +/- 1.26, P
      = 0.524), but the T/NT of (18)F-FLT differed significantly between SW480 and
      SW620 tumors (3.65 +/- 0.51 vs. 2.22 +/- 0.42, P < 0.001). Heat shock protein 27
      (HSP27) expression and integrin beta(3) expression were higher, whereas vascular
      endothelial growth factor receptor 2 (VEGFR2) expression and Ki67 expression were
      lower, in SW480 cells than in SW620 cells. For SW480, metastases in lung and
      liver correlated significantly with (18)F-FLT uptake in tumors (r = 0.763, P =
      0.005) and with expression of HSP27 (r = 0.894, P = 0.008) and integrin beta(3)
      (r = 0.635, P = 0.088). A correlation was also found between (18)F-FLT uptake and
      expression of HSP27 (r = 0.924, P = 0.004) and integrin beta(3) (r = 0.813, P =
      0.025). No correlation was found between (18)F-FDG uptake in tumors and
      metastasis in lung and liver (r = -0.111, P = 0.388). However, there was a
      significantly negative correlation between (18)F-FDG uptake and the survival time
      of tumor-bearing mice (r = -0.500, P = 0.017), to which (18)F-FLT did not relate
      (r = 0.262, P = 0.182). CONCLUSION: High uptake of (18)F-FDG and (18)F-FLT may
      reflect poorer survival and a higher metastatic potential for CRC in mice.
      Combining (18)F-FDG with (18)F-FLT PET would be helpful in better predicting the
      biologic behavior of CRC.

PMID- 19837755
TI  - 11C-PK11195 PET for the in vivo evaluation of neuroinflammation in the rat brain
      after cortical spreading depression.
AB  - Neurogenic inflammation triggered by extravasation of plasma protein has been
      hypothesized as a key factor in the generation of the pain sensation associated
      with migraine. The principal immune cell that responds to this inflammation is
      the parenchymal microglia of the central nervous system. METHODS: Using a PET
      technique with (11)C-(R)-[1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3
      isoquinolinecarboxamide] ((11)C-PK11195), a PET ligand for peripheral type
      benzodiazepine receptor, we evaluated the microglial activation in the rat brain
      after generation of unilateral cortical spreading depression, a stimulation used
      to bring up an experimental animal model of migraine. RESULTS: We found a
      significant increase in the brain uptake of (11)C-PK11195, which was completely
      displaceable by the excess amounts of unlabeled ligands, in the ipsilateral
      hemisphere of the spreading depression-generated rats. Moreover, the binding
      potential of (11)C-PK11195 in the spreading depression-generated rats was
      significantly higher than that in the sham-operated control rats. CONCLUSION:
      These results suggest that as an inflammatory reaction, microglial cells are
      activated in response to the nociceptive stimuli induced by cortical spreading
      depression in the rat brain. Therefore, the (11)C-PK11195 PET technique could
      have a potential for diagnostic and therapeutic monitoring of neurologic
      disorders related to neuroinflammation such as migraine.

PMID- 19837757
TI  - Assessment of interobserver reproducibility in quantitative 18F-FDG PET and CT
      measurements of tumor response to therapy.
AB  - Our goal was to estimate and compare across different readers the reproducibility
      of the (18)F-FDG PET standardized uptake value (SUV) and CT size measurements,
      and changes in those measurements, in malignant tumors before and after therapy.
      METHODS: Fifty-two tumors in 25 patients were evaluated on (18)F-FDG PET/CT
      scans. Maximum SUVs (SUV(bw) max) and CT size measurements were determined for
      each tumor independently on pre- and posttreatment scans by 8 different readers
      (4 PET, 4 CT) using routine nonautomated clinical methods. Percentage changes in
      SUV(bw) max and CT size between pre- and posttreatment scans were calculated.
      Interobserver reproducibility of SUV(bw) max, CT size, and changes in these
      values were described by intraclass correlation coefficients (ICCs) and estimates
      of variance. RESULTS: The ICC was higher for the pretreatment, posttreatment, and
      percentage change in SUV(bw) max than the ICC for the longest CT size and the 2
      dimensional CT size (before treatment, 0.93, 0.72, and 0.61, respectively; after
      treatment, 0.91, 0.85, and 0.45, respectively; and percentage change, 0.94, 0.70,
      and 0.33, respectively). The variability of SUV(bw) max was significantly lower
      than the variability of the longest CT size and the 2-dimensional CT size (mean
      +/- SD before treatment, 6.3% +/- 14.2%, 16.2% +/- 17.8%, and 27.5% +/- 26.7%,
      respectively, P < or = 0.001; and after treatment, 18.4% +/- 26.8%, 35.1% +/-
      47.5%, and 50.9% +/- 51.4%, respectively, P < or = 0.02). The variability of
      percentage change in SUV(bw) max (16.7% +/- 36.2%) was significantly lower than
      that for percentage change in the longest CT size (156.3% +/- 157.3%, P < or =
      0.0001) and the 2-dimensional CT size (178.4% +/- 546.5%, P < 0.0001).
      CONCLUSION: The interobserver reproducibility of SUV(bw) max for both untreated
      and treated tumors and percentage change in SUV(bw) max are substantially higher
      than measurements of CT size and percentage change in CT size. Measurements of
      tumor metabolism by PET should be included in trials to assess response to
      therapy. Although PET reproducibility was high, the variability observed in
      analyses of identical image sets by 4 readers indicates that automated analytic
      tools to assess response might be helpful to further enhance reproducibility.

PMID- 19837758
TI  - Prediction of the need for surgical intervention in obstructive Crohn's disease
      by 18F-FDG PET/CT.
AB  - We preoperatively determined the accuracy of (18)F-FDG PET/CT for differentiating
      fixed muscle hypertrophy and fibrotic stenoses from acute transmural inflammatory
      stenoses in patients with Crohn's disease (CD) scheduled to undergo surgical
      resection for obstructive symptoms. METHODS: Seventeen patients with known CD
      prospectively underwent (18)F-FDG PET/CT before already-planned surgery for
      obstructive symptoms. Image interpretation was by consensus of 2 readers with
      knowledge of patient participation in the study but not of other clinical
      history. Lesions were qualitatively graded on a 5-point scale for the presence of
      increased (18)F-FDG uptake consistent with active inflammation. Maximum lean
      standardized uptake value (SUL(max)) was determined for lesions scored 1 or more.
      Imaging results were compared with the pathologic grading of inflammation and
      predominant histopathologic subtype for each patient's surgical specimen, whether
      mainly inflammation, fibrosis, or muscle hypertrophy. RESULTS: Thirteen of the 17
      patients underwent surgery (median, 28 d after PET/CT; range, 2-148 d), and 12 of
      these 13 had histopathologic correlation. Despite the predominant histopathologic
      subtype (inflammation, 5; fibrosis, 4; and muscle hypertrophy, 3), acute and
      chronic inflammation, fibrosis (median, 50%; range, 40%-90%), and muscle
      hypertrophy (median, 20-fold thickening; range, 9- to 40-fold thickening) were
      found in all patients. SUL(max) was significantly higher in severe than in mild
      to-moderate chronic inflammation (8.2 +/- 2.8 vs. 4.7 +/- 2.5, P = 0.04). No
      patient with predominantly fibrosis or muscle hypertrophy (n = 7) had an SUL(max)
      greater than 8. Visually, 10 of 12 patients on PET/CT were considered to have
      active inflammation of the bowel. CONCLUSION: Patients with CD who undergo
      surgery for obstructive symptoms have histopathologically mixed findings of
      inflammation, fibrosis, and muscle hypertrophy. Qualitative PET interpretations
      were quite sensitive, but additional semiquantitative analyses using SUL(max)
      helped identify patients with active inflammation. This information may be
      beneficial for referring gastroenterologists considering medical therapy versus
      surgery for patients with CD who present with obstructive symptoms.

PMID- 19837759
TI  - Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain.
AB  - beta-amyloid plaques (Abeta plaques) in the brain, containing predominantly
      fibrillary Abeta peptide aggregates, represent a defining pathologic feature of
      Alzheimer disease (AD). Imaging agents targeting the Abeta plaques in the living
      human brain are potentially valuable as biomarkers of pathogenesis processes in
      AD. (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N
      methyl benzenamine ((18)F-AV-45) is such as an agent currently in phase III
      clinical studies for PET of Abeta plaques in the brain. METHODS: In vitro binding
      of (18)F-AV-45 to Abeta plaques in the postmortem AD brain tissue was evaluated
      by in vitro binding assay and autoradiography. In vivo biodistribution of (18)F
      AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1)
      with Abeta aggregates in the brain were performed. Small-animal PET of a monkey
      brain after an intravenous injection of (18)F-AV-45 was evaluated. RESULTS: (18)F
      AV-45 displayed a high binding affinity and specificity to Abeta plaques (K(d),
      3.72 +/- 0.30 nM). In vitro autoradiography of postmortem human brain sections
      showed substantial plaque labeling in AD brains and not in the control brains.
      Initial high brain uptake and rapid washout from the brain of healthy mice and
      monkey were observed. Metabolites produced in the blood of healthy mice after an
      intravenous injection were identified. (18)F-AV-45 displayed excellent binding
      affinity to Abeta plaques in the AD brain by ex vivo autoradiography in
      transgenic AD model mice. The results lend support that (18)F-AV-45 may be a
      useful PET agent for detecting Abeta plaques in the living human brain.

PMID- 19837760
TI  - 18F-FDG small-animal PET/CT differentiates trastuzumab-responsive from
      unresponsive human breast cancer xenografts in athymic mice.
AB  - Breast cancers (BCs) with high human epidermal growth factor receptor type 2
      (HER2) expression are most likely to respond to trastuzumab; however, the
      mechanisms of action of trastuzumab are complex and there are no established
      biomarkers to accurately monitor treatment outcome in individual patients.
      Therefore, our aim was to determine, in human BC xenografts in athymic mice
      treated with trastuzumab, whether there were any changes in (18)F-FDG uptake that
      were associated with response to the drug and that could have utility in
      monitoring response in patients. METHODS: Baseline tumor uptake of (18)F-FDG was
      measured in mice with MDA-MB-361 HER2-overexpressing xenografts and MDA-MB-231
      xenografts with low HER2 expression by small-animal PET imaging on day 0. Mice
      were treated with phosphate-buffered saline (PBS) or trastuzumab (4 mg/kg), and
      small-animal PET was repeated 2 d after treatment. Maintenance doses of
      trastuzumab (2 mg/kg) or PBS were administered on days 7 and 14, and mice were
      imaged again on days 9 and 16. Tumor uptake was measured as percentage injected
      dose per gram (%ID/g) by volume-of-interest analysis on days 0 (baseline), 2, 9,
      and 16, followed by biodistribution studies on day 16. Tumor growth was measured,
      and a tumor growth index was calculated. RESULTS: The treatment of mice with
      trastuzumab, compared with control mice treated with PBS, resulted in a
      significant decrease in tumor uptake of (18)F-FDG in HER2-overexpressing MDA-MB
      361 xenografts after 16 d of treatment (2.6 +/- 0.8 %ID/g vs. 4.6 +/- 1.8 %ID/g,
      respectively; P < 0.03) but not after 2 or 9 d of treatment (P = 0.28-0.32). In
      contrast, there was no significant change in the tumor uptake of MDA-MB-231
      xenografts with low HER2 expression during the entire course of therapy (4.4 +/-
      1.7 %ID/g vs. 3.6 +/- 1.1 %ID/g, respectively; P = 0.31). Trastuzumab treatment,
      compared with PBS treatment of controls, resulted in significant growth
      inhibition of MDA-MB-361 xenografts as early as 10 d from the initiation of
      treatment (tumor growth index, 0.7 +/- 0.2 vs. 1.7 +/- 0.3, respectively; P <
      0.0005), whereas no tumor growth inhibition was observed for MDA-MB-231
      xenografts (5.3 +/- 2.7 and 5.2 +/- 3.0; P = 0.95). CONCLUSION: Changes in the
      tumor uptake of (18)F-FDG after therapy accurately identified responding and
      nonresponding human BC xenografts in athymic mice treated with trastuzumab;
      however, diminished glucose utilization did not precede changes in tumor volume.

PMID- 19837761
TI  - Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in
      treatment of non-small cell lung cancer with the mTOR inhibitor everolimus.
AB  - Everolimus downregulates glucose metabolism-associated genes in preclinical
      models. Inhibition of glucose metabolism measured by (18)F-FDG PET was postulated
      to serve as a pharmacodynamic marker in everolimus-treated non-small cell lung
      cancer (NSCLC) patients. METHODS: In 8 NSCLC patients treated with everolimus,
      the percentage change in (18)F-FDG PET uptake (days 8 and 28 relative to
      baseline) was determined using a variety of summed standardized uptake value
      (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body
      surface area and body weight and with and without correcting for plasma glucose
      levels. RESULTS: In 5 patients, a reduction of (18)F-FDG PET uptake on day 8 was
      observed with all methods, ranging from -12.8% to -72.2%. CONCLUSION: These
      observations demonstrate that inhibition of glucose metabolism is an early effect
      of everolimus treatment in NSCLC patients and can be assessed using (18)F-FDG
      PET.

PMID- 19837762
TI  - Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for
      immuno-PET in head and neck cancer patients.
AB  - Immuno-PET is an appealing concept in the detection of tumors and planning of
      antibody-based therapy. For this purpose, the long-lived positron emitter (89)Zr
      (half-life, 78.4 h) recently became available. The aim of the present first-in
      humans (89)Zr immuno-PET study was to assess safety, biodistribution, radiation
      dose, and quantification of the (89)Zr-labeled chimeric monoclonal antibody
      (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In
      addition, the performance of immuno-PET for detecting lymph node metastases was
      evaluated, as described previously. METHODS: Twenty HNSCC patients, scheduled to
      undergo surgical tumor resection, received 75 MBq of (89)Zr-cmAb U36 (10 mg).
      Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The
      biodistribution of the radioimmunoconjugate was evaluated by ex vivo
      radioactivity measurement in blood and in biopsies from the surgical specimen
      obtained at 168 h after injection. Uptake levels and residence times in blood,
      tumors, and organs of interest were derived from quantitative immuno-PET studies,
      and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was
      calculated using the residence time for blood. RESULTS: (89)Zr-cmAb U36 was well
      tolerated by all subjects. PET quantification of blood-pool activity in the left
      ventricle of the heart showed a good agreement with sampled blood activity
      (difference equals 0.2% +/- 16.9% [mean +/- SD]) except for heavy-weight patients
      (>100 kg). A good agreement was also found for the assessment of mAb uptake in
      primary tumors (mean deviation, -8.4% +/- 34.5%). The mean absorbed red marrow
      dose was 0.07 +/- 0.02 mSv/MBq and 0.09 +/- 0.01 mSv/MBq in men and women,
      respectively. The normal organ with the highest absorbed dose was the liver (mean
      dose, 1.25 +/- 0.27 mSv/MBq in men and 1.35 +/- 0.21 mSv/MBq in women),
      thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective
      dose was 0.53 +/- 0.03 mSv/MBq in men and 0.66 +/- 0.03 mSv/MBq in women.
      Measured excretion via the urinary tract was less than 3% during the first 72 h.
      CONCLUSION: (89)Zr immuno-PET can be safely used to quantitatively assess
      biodistribution, uptake, organ residence times, and radiation dose, justifying
      its further clinical exploitation in the detection of tumors and planning of mAb
      based therapy.

PMID- 19837763
TI  - Neuroinflammation in schizophrenia-related psychosis: a PET study.
AB  - Schizophrenia is a chronic and disabling brain disease characterized by psychotic
      episodes with unknown etiology. It is suggested that neuroinflammation plays a
      role in the pathophysiology of schizophrenia. Neuroinflammation is characterized
      by the activation of microglia cells, which show an increase in the expression of
      the peripheral benzodiazepine receptor. The isoquinoline (R)-N-(11)C-methyl-N-(1
      methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide ((11)C-(R)-PK11195) is
      a peripheral benzodiazepine receptor ligand that can be used for the imaging of
      activated microglia cells, and thus neuroinflammation, with PET. We hypothesized
      that neuroinflammation would be more profound in schizophrenic patients during
      psychosis, and it was therefore investigated whether neuroinflammation was
      present in patients within the schizophrenia spectrum who were in a psychotic
      phase. METHODS: Seven patients within the schizophrenia spectrum who were
      recovering from psychosis were included. Recovering psychosis was defined by a
      score of 5 or more on 1 item of the positive scale of the positive and negative
      symptoms scale (PANSS) or a score of 4 on 2 items. The patients were compared
      with 8 age-matched healthy volunteers. Dynamic 60-min PET scans were acquired
      after the injection of (11)C-(R)-PK11195. All subjects underwent T1- and T2
      weighted MRI, and the scans were visually examined for abnormalities and used for
      anatomic coregistration in data analysis. The PET data were analyzed with a 2
      tissue-compartment model to calculate the binding potential, using the metabolite
      corrected plasma curve as input. RESULTS: A significantly higher binding
      potential of (11)C-(R)-PK11195, indicative of neuroinflammation, was found in the
      hippocampus of schizophrenic patients than in healthy volunteers (2.07 +/- 0.42
      vs. 1.37 +/- 0.30; P = 0.004). A nonsignificant 30% higher (11)C-(R)-PK11195
      binding potential was found in the whole-brain gray matter of schizophrenic
      patients. The MR images did not reveal any visual abnormalities. CONCLUSION: The
      present study suggests that focal neuroinflammation may play an important role in
      schizophrenia during psychosis.

PMID- 19837764
TI  - Dosimetry of 90Y-ibritumomab tiuxetan as consolidation of first remission in
      advanced-stage follicular lymphoma: results from the international phase 3 first
      line indolent trial.
AB  - The objective of this analysis was to assess the radiation exposure associated
      with (90)Y-ibritumomab tiuxetan when used as consolidation therapy in adults with
      low or minimal tumor burden after first-line therapy of advanced follicular
      lymphoma (FL). METHODS: The patients who were enrolled in the phase 3 first-line
      indolent trial were 18 y or older, with CD20(+) grade 1 or 2 stage III or IV FL,
      and a partial response, complete response, or unconfirmed complete response to
      first-line chemotherapy. The patients were allocated randomly to receive a single
      infusion of unlabeled rituximab 250 mg/m(2) on day -7 and consolidation on day 0
      with a single dose of (90)Y-ibritumomab tiuxetan, 14.8 MBq/kg, immediately after
      unlabeled rituximab, 250 mg/m(2), or no further treatment. On day -7, a subset of
      patients received an injection of 185 MBq of (111)In-ibritumomab tiuxetan
      immediately after unlabeled rituximab, 250 mg/m(2), for central dosimetry
      analysis. Correlations were assessed between organ radiation absorbed dose and
      toxicity, body weight, body mass index, and progression-free survival. RESULTS:
      Central dosimetry evaluations were available from 57 of 70 patients. Median
      radiation absorbed doses were 100 cGy (range, 28-327 cGy) for the red marrow and
      72 cGy (range, 46-106 cGy) for the whole body. Radiation absorbed doses did not
      differ significantly between patients who had a partial response or complete
      response to initial therapy. Progression-free survival correlated significantly
      with the whole-body (r = 0.4401; P = 0.0006) and bone marrow (r = 0.2976; P =
      0.0246) radiation dose. Body weight was significantly negatively correlated with
      whole-body radiation dose (r = -0.4971; P < 0.0001). Neither the whole-body
      radiation dose nor the bone marrow radiation dose correlated with hematologic
      toxicity. CONCLUSION: In patients with low or minimal residual tumor burden after
      first-line chemotherapy of advanced FL, whole-body and bone marrow exposure after
      (90)Y-ibritumomab tiuxetan consolidation showed a significant positive
      correlation with progression-free survival, whereas dosimetric data could not
      predict hematologic toxicity.

PMID- 19837765
TI  - 99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular
      neoplasms: relationship to multidrug resistance protein expression.
AB  - Recently, thyroid (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintiscanning
      has been proposed in an attempt to preoperatively identify thyroid malignancies,
      but discrepant results have been reported for oncocytic lesions. The aim of this
      study was to investigate the usefulness of visual and semiquantitative analyses
      of (99m)Tc-MIBI scintigraphy for preoperatively characterizing thyroid nodules
      with indeterminate cytologic diagnoses, segregating in advance nononcocytic
      variants from those that are oncocytic. This study also aimed to analyze the
      relationship between (99m)Tc-MIBI images and P-glycoprotein (P-gp)/multidrug
      resistance-associated protein-1 (MRP1) immunohistochemical expression. METHODS:
      Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed
      as nononcocytic or oncocytic follicular neoplasm were prospectively studied.
      Visual and semiquantitative (99m)Tc-MIBI scanning was performed and the diagnoses
      of the lesions were histologically proven by subsequent thyroidectomy.
      Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical
      samples. RESULTS: Visual and semiquantitative (99m)Tc-MIBI scintiscans showed a
      low specificity in preoperatively discriminating malignant oncocytic lesions. In
      nononcocytic nodules, the semiquantitative method was more accurate than the
      visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in
      all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in
      78% of the lesions with a negative (99m)Tc-MIBI retention index, compared with
      11% of lesions with a positive retention index, correlating most strongly with a
      negative (99m)Tc-MIBI RI in those cases with strong MRP1 apical expression.
      CONCLUSION: Semiquantitative (99m)Tc-MIBI scintigraphy is an adjunctive method to
      predict preoperatively the malignant behavior of nononcocytic follicular thyroid
      nodules indeterminate at fine-needle aspiration biopsy, with a potential impact
      on the definition of their clinical management. Moreover, the good correlation
      found between immunohistochemical apical expression of MRP1 and the scintigraphic
      findings supports the (99m)Tc-MIBI results and provides tissue information on the
      molecular mechanisms responsible for (99m)Tc-MIBI images in thyroid lesions.

PMID- 19837766
TI  - Effects of alendronate on bone metabolism in glucocorticoid-induced osteoporosis
      measured by 18F-fluoride PET: a prospective study.
AB  - Osteoporosis represents a significant side effect of glucocorticoid therapy, and
      alendronate has been reported to prevent this glucocorticoid-induced
      osteoporosis. Functional imaging with (18)F-fluoride PET allows quantitative
      analysis of bone metabolism in specific skeletal regions. However, only a few
      studies have quantitatively determined bone turnover and metabolism in
      glucocorticoid-induced osteoporosis by radiologic imaging techniques including
      PET. The aim of this study was to examine changes in regional bone remodeling and
      turnover as measured by (18)F-fluoride PET, the relationship between these
      measured changes and conventional bone metabolism parameters, and the effect of
      alendronate treatment. METHODS: The study group consisted of 24 postmenopausal
      women (mean age, 59.7 y) who had various diseases, excluding rheumatoid
      arthritis, and had been treated with 10 mg or more of oral glucocorticoids
      (prednisolone equivalent) per day for more than 6 mo. Treatment with 5 mg of
      alendronate per day began at the time of study entry and continued for 12 mo.
      (18)F-fluoride PET was performed at baseline, 3 mo, and 12 mo to determine
      localized bone turnover, and the results were compared with other bone metabolism
      parameters. RESULTS: Lumbar spine standardized uptake values (SUVs) were
      significantly lower (P < 0.05) in the osteoporotic group (T-score < or = -2.5)
      than in the group that was healthy or osteopenic (T-score > -2.5). Patients
      treated with alendronate for 12 mo exhibited significant decreases in serum bone
      specific alkaline phosphate (P < 0.05), urinary N-telopeptide for type I collagen
      (P < 0.01), lumbar spine SUV (P < 0.01), and femoral neck SUV (P < 0.01) in
      association with a gradual increase in bone mineral density (BMD) of the lumbar
      spine relative to the baseline value (P < 0.05). Although there was a significant
      correlation between BMD and SUV in the lumbar spine at baseline (P < 0.05), there
      was no correlation between the 2 variables at 12 mo of treatment with
      alendronate. CONCLUSION: Alendronate treatment resulted in significant decreases
      in bone metabolism and turnover in the lumbar spine. It also led to an increase
      in BMD of the lumbar spine in patients with glucocorticoid-induced osteoporosis.
      Our findings suggest that antiresorptive therapy has a direct bone-metabolism
      effect on skeletal kinetics in glucocorticoid-induced osteoporosis at the
      clinically important site of the lumbar spine.

PMID- 19837768
TI  - 18F-FMT uptake seen within primary cancer on PET helps predict outcome of non
      small cell lung cancer.
AB  - L-[3-(18)F]-alpha-methyl tyrosine ((18)F-FMT) is an amino-acid tracer for PET
      imaging. We evaluated the prognostic significance of (18)F-FMT PET in patients
      with non-small cell lung cancer. METHODS: Ninety-eight patients (80 men and 18
      women; age range, 42-82 y; median age, 69 y) with stage I-IV non-small cell lung
      cancer were enrolled in this study. They included 57 with adenocarcinoma, 31 with
      squamous cell carcinoma, 5 with large cell carcinoma, and 5 with other
      conditions. The median follow-up duration was 17.0 mo. A pair of PET studies with
      (18)F-FMT and (18)F-FDG was performed, and tracer uptake by the primary tumor was
      evaluated using the maximal standardized uptake value (SUV(max)). Overall
      survival and disease-free survival were calculated by the Kaplan-Meier method.
      The prognostic significance was assessed by univariate and multivariate analyses.
      RESULTS: The best discriminative SUV(max) cutoffs for (18)F-FMT and (18)F-FDG in
      the primary tumors were 1.6 and 11, respectively. In the univariate analysis, a
      high SUV(max) was significant in predicting poor overall survival for (18)F-FMT
      (P = 0.0129) and (18)F-FDG PET (P = 0.0481). According to histologic types, (18)F
      FMT and (18)F-FDG uptake were a stronger prognostic predictor in adenocarcinoma
      than in nonadenocarcinomatous disease. Patients with a high SUV(max) for (18)F
      FMT showed significantly worse disease-free survival rates than those with a low
      SUV(max), and multivariate analysis confirmed that a high SUV(max) for (18)F-FMT
      was an independent and significant factor in predicting a poor prognosis in
      patients with adenocarcinoma (P = 0.0191). CONCLUSION: Uptake of (18)F-FMT in
      primary tumors was an independent prognostic factor in patients with pulmonary
      adenocarcinoma.

PMID- 19837767
TI  - 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates
      and disease characterization.
AB  - It is hoped that in the not too distant future, noninvasive imaging-based
      molecular interrogation and characterization of tumors can improve our
      fundamental understanding of the dynamic biologic behavior of cancer. For
      example, the new dimension of diagnostic information that is provided by (18)F
      FDG PET has led to improved clinical decision making and management changes in a
      substantial number of patients with cancer. In this context, the aim of this
      review is to bring together and summarize the current data on the correlation
      between the underlying molecular biology and the clinical observations of tumor
      (18)F-FDG accumulation in 3 major human cancers: lung, breast, and colon.

PMID- 19837769
TI  - Using cerebral white matter for estimation of nondisplaceable binding of 5-HT1A
      receptors in temporal lobe epilepsy.
AB  - The estimation of nondisplaceable binding from cerebellar white matter, rather
      than from whole cerebellum, was proposed for the PET tracer carbonyl-(11)C-WAY
      100635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2
      pyridyl)cyclohexanecarboxamidel]) because of the heterogeneity of total ligand
      binding in this region. For the 5-hydroxytryptamine receptor 1A (5-HT(1A))
      antagonist (18)F-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-2-pyridyl)trans
      4-fluorocyclohexanecarboxamide ((18)F-FCWAY), the estimation of nondisplaceable
      binding from cerebellum (V(ND)) may be additionally biased by spillover of (18)F
      fluoride activity from skull. We aimed to assess the effect of using cerebral
      white matter as reference region on detection of group differences in 5-HT(1A)
      binding with PET and (18)F-FCWAY. METHODS: In 22 temporal lobe epilepsy patients
      (TLE) and 10 healthy controls, (18)F-FCWAY distribution volume in cerebral white
      matter (V(WM)) was computed using an extrapolation method as part of a partial
      volume correction (PVC) algorithm. To assess the feasibility of applying this
      method to clinical studies in which PVC is not performed, V(WM) was also
      calculated by placing circular, 6-mm-diameter regions of interest (ROIs) in the
      centrum semiovalis on parametric images. Binding potentials were BP(F) = (V(T) -
      V(ND))/f(P) and BP(F-WM) = (V(T) - V(WM))/f(P), where V(T) is total distribution
      volume and f(P) = (18)F-FCWAY plasma free fraction. Statistical analysis was
      performed using t tests and linear regression. RESULTS: In the whole group, V(WM)
      was 14% +/- 19% lower than V(ND) (P < 0.05). V(WM)/f(P) was significantly (P <
      0.05) lower in patients than in controls. All significant (P < 0.05) reductions
      of 5-HT(1A) receptor availability in TLE patients detected by BP(F) were also
      detected using BP(F-WM). Significant (P < 0.05) reductions of 5-HT(1A) specific
      binding were detected by BP(F-WM), but not BP(F), in ipsilateral inferior
      temporal cortex, contralateral fusiform gyrus, and contralateral amygdala.
      However, effect sizes were similar for BP(F-WM) and BP(F). The value of V(WM)
      calculated with the ROI approach did not significantly (P > 0.05) differ from
      that calculated with the extrapolation approach (0.67 +/- 0.32 mL/mL and 0.72 +/-
      0.34 mL/mL, respectively). CONCLUSION: Cerebral white matter can be used for the
      quantification of nondisplaceable binding of 5-HT(1A) without loss of statistical
      power for detection of regional group differences. The ROI approach is a good
      compromise between computational complexity and sensitivity to spillover of
      activity, and it appears suitable to studies in which PVC is not performed. For
      (18)F-FCWAY, this approach has the advantage of avoiding spillover of (18)F
      fluoride activity onto the reference region.

PMID- 19837770
TI  - Reporter gene PET for monitoring survival of transplanted endothelial progenitor
      cells in the rat heart after pretreatment with VEGF and atorvastatin.
AB  - It has been suggested that vascular endothelial growth factor (VEGF) and statins
      enhance the survival, proliferation, and function of endothelial progenitor cells
      (EPCs). We investigated whether reporter gene PET can be used to detect the
      effects of atorvastatin and VEGF on survival of EPCs after transplantation in the
      rat heart. METHODS: Healthy nude rats received an intramyocardial injection of 4
      million human EPCs retrovirally transduced with the sodium/iodide symporter gene
      for reporter gene imaging. Reporter gene expression was imaged at days 1 and 3
      after injection on a small-animal PET scanner with (124)I, and the presence of
      EPCs was confirmed by immunohistochemistry with human CD31 antibodies. The
      control group received EPCs transduced only with the reporter gene, whereas
      treatment groups received oral atorvastatin (10 mg/kg/d) and EPCs cotransduced
      with adenoviral vectors encoding VEGF in addition to sodium/iodide symporter.
      RESULTS: Immunohistochemistry showed more EPCs at the site of injection after
      atorvastatin treatment and in the presence of VEGF expression in EPCs than in
      controls. PET successfully visualized EPCs as focal (124)I accumulation at the
      site of injection. The quantitative amount of (124)I accumulation assessed by PET
      was significantly higher in the pretreatment than control group. Autoradiography
      confirmed (124)I accumulation in the myocardium that correlated with the number
      of EPCs. CONCLUSION: Early survival of transplanted EPCs in the rat myocardium is
      prolonged by pretreatment with a combination of atorvastatin and VEGF. Reporter
      gene PET, by successfully quantifying the effect, is an attractive tool for
      monitoring stem cell survival in vivo.

PMID- 19837771
TI  - 124I PET-based 3D-RD dosimetry for a pediatric thyroid cancer patient: real-time
      treatment planning and methodologic comparison.
AB  - Patient-specific 3-dimensional radiobiologic dosimetry (3D-RD) was used for
      (131)I treatment planning for an 11-y-old girl with differentiated papillary
      thyroid cancer, heavy lung involvement, and cerebral metastases. (124)I PET was
      used for pharmacokinetics. Calculation of the recommended administered activity,
      based on lung toxicity constraints, was performed in real time (i.e., during the
      data-acquisition interval). The results were available to the physician in time
      to influence treatment; these estimates were compared with conventional dosimetry
      methodologies. In subsequent, retrospective analyses, the 3D-RD calculations were
      expanded to include additional tumor dose estimates, and the conventional
      methodologies were reexamined to reveal the causes of the differences observed. A
      higher recommended administered activity than by an S-value-based method with a
      favorable clinical outcome was obtained. This approach permitted more aggressive
      treatment while adhering to patient-specific lung toxicity constraints. A
      retrospective analysis of the conventional methodologies with appropriate
      corrections yielded absorbed dose estimates consistent with 3D-RD.

PMID- 19837772
TI  - Recovery of heart rate following intense dynamic exercise.
AB  - The Olympic biathlon is a very demanding physical event that requires high oxygen
      delivery, good cross-country skiing skills and skilful use of a rifle. Like all
      high-performance endurance athletes, high cardiac vagal tone is a characteristic
      and extends the range over which cardiac output can increase. In the biathlete,
      however, the enhanced vagal control of the heart also allows a strategy for
      better control of stability needed for accurately firing a rifle at the end of
      each lap of the race. The role of endurance training, central command, reflexes
      from muscle, and of the carotid-cardiac baroreceptor reflex in changing vagal
      tone during intense exercise and recovery is discussed.

PMID- 19837773
TI  - Altitude training considerations for the winter sport athlete.
AB  - Winter sports events routinely take place at low to moderate altitudes, and
      nearly all Winter Olympic Games have had at least one venue at an altitude >1000
      m. The acute and chronic effects of altitude can have a substantial effect on
      performance outcomes. Acutely, the decline in oxygen delivery to working muscle
      decreases maximal oxygen uptake, negatively affecting performance in endurance
      events, such as cross-country skiing and biathlon. The reduction in air
      resistance at altitude can dramatically affect sports involving high velocities
      and technical skill components, such as ski jumping, speed skating, figure
      skating and ice hockey. Dissociation between velocity and sensations usually
      associated with work intensity (ventilation, metabolic signals in skeletal muscle
      and heart rate) may impair pacing strategy and make it difficult to determine
      optimal race pace. For competitions taking place at altitude, a number of
      strategies may be useful, depending on the altitude of residence of the athlete
      and ultimate competition altitude, as follows. First, allow extra time and
      practice (how much is yet undetermined) for athletes to adjust to the changes in
      projectile motion; hockey, shooting, figure skating and ski jumping may be
      particularly affected. These considerations apply equally in the reverse
      direction; that is, for athletes practising at altitude but competing at sea
      level. Second, allow time for acclimatization for endurance sports: 3-5 days if
      possible, especially for low altitude (500-2000 m); 1-2 weeks for moderate
      altitude (2000-3000 m); and at least 2 weeks if possible for high altitude (>3000
      m). Third, increase exercise-recovery ratios as much as possible, with 1:3 ratio
      probably optimal, and consider more frequent substitutions for sports where this
      is allowed, such as ice hockey. Fourth, consider the use of supplemental O(2) on
      the sideline (ice hockey) or in between heats (skating and Alpine skiing) to
      facilitate recovery. For competitions at sea level, the 'live high-train low'
      model of altitude training can help athletes in endurance events to maximize
      performance.

PMID- 19837775
TI  - Local adaptation in human trained skeletal muscle could preferentially bind blood
      interleukin-6.

PMID- 19837774
TI  - Aldosterone synthesis in the brain contributes to Dahl salt-sensitive rat
      hypertension.
AB  - The enzymes required for aldosterone synthesis from cholesterol are expressed in
      rat and human brains. The hypertension of Dahl salt-sensitive (SS) rats is
      mitigated by the intracerebroventricular (i.c.v.) infusion of antagonists of the
      mineralocorticoid receptor (MR) and downstream effectors of mineralocorticoid
      action, as well as ablations of brain areas that also abrogate mineralocorticoid
      salt excess hypertension in normotensive rats. We used real time RT-PCR to
      measure mRNA of aldosterone synthase and 11beta-hydroxylase, the requisite
      enzymes for the last step in the synthesis of aldosterone and corticosterone,
      respectively, MR and the determinants of MR ligand specificity, 11beta
      hydroxysteroid dehydrogenase types 1 and 2 (11beta-HSD1&2) and hexose-6-phosphate
      dehydrogenase (H6PDH). A combination of extraction and ELISA was used to measure
      aldosterone concentrations in tissue and urine of SS and Sprague-Dawley (SD)
      rats. Aldosterone synthase mRNA expression was higher in the brains and lower in
      the adrenal glands of SS compared with SD rats. The amounts of mRNA for MR,
      11beta-hydroxylase, 11beta-HSD1&2 and H6PD were similar. Aldosterone
      concentrations were greater in brains of SS than SD rats, yet, in keeping with
      the literature, the circulating and total aldosterone production of aldosterone
      in SS rats were not. The selective inhibitor of aldosterone synthase, FAD286, was
      infused i.c.v. or subcutaneously in a cross-over blood pressure study in
      hypertensive SS rats further challenged by a high-salt diet. The i.c.v. infusion
      of FAD286, at a dose that had no effect systemically, significantly and
      reversibly lowered blood pressure in SS rats. Aldosterone synthesis in brains of
      SS rats is greater than in SD rats and is important in the genesis of their salt
      sensitive hypertension.

PMID- 19837776
TI  - Central command and cerebral blood flow during exercise.

PMID- 19837777
TI  - The cultural formulation.

PMID- 19837778
TI  - Cultural formulation guidelines.
AB  - The outline for the Cultural Formulation (CF) introduced in DSM-IV does not
      present any method for collecting the required cultural information. The absence
      of specific guidelines and illustrative cases has hampered its wider use. This
      article offers a practical approach to preparing a Cultural Formulation as a
      component of culturally competent clinical care. We summarize the rationale for
      the four sections of the CF, describe the process of conducting culturally
      focused clinical interviews, and present examples of questions or lines of
      inquiry that can be used to collect the information needed to construct the CF.
      An online supplement provides case examples of cultural formulations applied to
      patients seen in the US.

PMID- 19837779
TI  - The cultural formulation: A model to combine nosology and patients' life context
      in psychiatric diagnostic practice.
AB  - This article discusses the experience of adapting and applying the Outline for a
      Cultural Formulation in DSM-IV to the Swedish context. Findings from a research
      project on the Cultural Formulation highlight the value of combining psychiatric
      nosological categorization with an understanding of patients' cultural life
      context in order to increase the validity of categorization and to formulate
      individualized treatment plans. In clinical care practitioners need models and
      tools that help them take into account patients' cultural backgrounds, needs, and
      resources in psychiatric diagnostic practice. We present a summary of a Swedish
      manual for conducting a Cultural Formulation interview. The need for further
      development of the Cultural Formulation is also discussed.

PMID- 19837780
TI  - A qualitative study of clinicians' use of the cultural formulation model in
      assessing posttraumatic stress disorder.
AB  - The Cultural Formulation (CF) of the Diagnostic and Statistical Manual (DSM)
      provides a potential framework for improving the diagnostic assessment of
      Posttraumatic Stress Disorder (PTSD) in culturally diverse patients. We analyzed
      data from the Patient-Provider Encounter Study, a multi-site study that examines
      the process of diagnosis and clinical decision-making during an initial clinical
      intake session, in order to examine use of CF for PTSD diagnosis. We find that
      while the CF is generally used inconsistently or underutilized in routine
      community settings, when employed appropriately it may assist the formulation and
      interpretation of traumatic experiences. We discuss the implications for
      improving the assessment of PTSD in the time-limited setting of the clinical
      intake encounter and across race/ethnicity.

PMID- 19837781
TI  - Recognizing cultural identity in mental health care: Rethinking the cultural
      formulation of a somali patient.
AB  - Although there are many ways to produce a cultural formulation that facilitates a
      culturally sensitive diagnosis and treatment for asylum seekers and refugees in
      mental health care, it is essential to gain trust and 'recognize' the patient.
      One way to achieve this recognition is through a cultural interview, in which
      cultural references of the health care provider and the patient are exchanged.
      This paper presents an example of such a process with a Somali migrant to the
      Netherlands, whose passivity and inactivity puzzled the psychiatrist. Gaining his
      trust and recognizing his cultural roots as a member of a Somali ethnic group
      revealed more about his motives, concepts and attitude. This example suggests the
      importance of cultural identity as a way to explore the meanings of the illness
      and the interrelationship between the patient and health care provider. The
      cultural identity of the patient is a basis on which meanings can be exchanged in
      an ongoing way and starting points for effective treatment can be found.

PMID- 19837782
TI  - Clinical pitfalls in the diagnosis of ataque de nervios: a case study.
AB  - Ataque de nervios (attack of nerves) is an idiom of distress generally thought of
      in relation to Caribbean Hispanics. The following case study discusses the
      presentation of ataque de nervios in a Colombian female. This case study provides
      insight into a different presentation of ataque de nervios in a new population
      that clinicians should be aware of in order to ensure accurate diagnosis. Ataque
      de nervios is a distinct syndrome that does not fully correspond with any single
      DSM-IV diagnosis. However, there is overlap between symptoms in this condition
      and those in conventional clinical diagnoses. Common problems in deriving an
      accurate differential diagnosis are discussed. Implications for treatment are
      also reviewed, with an emphasis on a comprehensive approach to treatment that
      supports the client's norms and values.

PMID- 19837783
TI  - Use of the cultural formulation with refugees.
AB  - This article discusses the experiences of mental health professionals who applied
      the Cultural Formulation (CF) of the DSM-IV for assessment of psychopathology and
      treatment needs of refugees in the Netherlands. The CF approach proved to be a
      useful tool in the assessment and diagnostic phase of clinical treatment.
      However, patients reported problems with defining their own culture and providing
      explanations of illness and therapists had difficulty identifying culturally
      based difficulties in the clinical relationship. Additional information was
      needed about working with interpreters, therapists' attitudes towards the culture
      of the patient and towards their own culture, patients' previous experiences with
      discrimination and inaccessibility of care, gender issues, and specific cultures
      and subcultures. A more structured approach to conducting the CF is recommended.
      We developed the "Cultural Formulation Interview" for this purpose. The
      adaptations are aimed at improving the CF for use with refugee populations, as
      well as for more general use in transcultural psychiatry.

PMID- 19837784
TI  - DSM-IV-TR cultural formulation of psychiatric cases: Two proposals for
      clinicians.
AB  - This article reviews some limitations of the current guideline for the DSM-IV-TR
      Cultural Formulation (CF) from the perspective of psychiatric practice that are
      based on the author's experience conducting doctoral courses on cultural
      psychiatry from 1996 to 2007 in the Department of Psychiatry at the Universidad
      Autonoma de Madrid (Spain). Two proposals are presented for facilitating use of
      the CF by general clinicians. These proposals offer a procedure for embedding
      only the most relevant clinical information in a psychiatric history, followed by
      a brief cultural formulation. The approach is illustrated with a clinical case.
      Although the CF has considerable promise for revealing knowledge about patients,
      health practices, and health systems that is essential for clinical care,
      substantial research must be carried out to facilitate widespread use of the CF
      in clinical practice.

PMID- 19837785
TI  - What do we mean by "Asian"?

PMID- 19837786
TI  - Diabetes distress but not clinical depression or depressive symptoms is
      associated with glycemic control in both cross-sectional and longitudinal
      analyses.
AB  - OBJECTIVE: To determine the concurrent, prospective, and time-concordant
      relationships among major depressive disorder (MDD), depressive symptoms, and
      diabetes distress with glycemic control. RESEARCH DESIGN AND METHODS: In a
      noninterventional study, we assessed 506 type 2 diabetic patients for MDD
      (Composite International Diagnostic Interview), for depressive symptoms (Center
      for Epidemiological Studies-Depression), and for diabetes distress (Diabetes
      Distress Scale), along with self-management, stress, demographics, and diabetes
      status, at baseline and 9 and 18 months later. Using multilevel modeling (MLM),
      we explored the cross-sectional relationships of the three affective variables
      with A1C, the prospective relationships of baseline variables with change in A1C
      over time, and the time-concordant relationships with A1C. RESULTS: All three
      affective variables were moderately intercorrelated, although the relationship
      between depressive symptoms and diabetes distress was greater than the
      relationship of either with MDD. In the cross-sectional MLM, only diabetes
      distress but not MDD or depressive symptoms was significantly associated with
      A1C. None of the three affective variables were linked with A1C in prospective
      analyses. Only diabetes distress displayed significant time-concordant
      relationships with A1C. CONCLUSIONS: We found no concurrent or longitudinal
      association between MDD or depressive symptoms with A1C, whereas both concurrent
      and time-concordant relationships were found between diabetes distress and A1C.
      What has been called "depression" among type 2 diabetic patients may really be
      two conditions, MDD and diabetes distress, with only the latter displaying
      significant associations with A1C. Ongoing evaluation of both diabetes distress
      and MDD may be helpful in clinical settings.

PMID- 19837787
TI  - Pro12Ala polymorphism in the PPARG gene contributes to the development of
      diabetic nephropathy in Chinese type 2 diabetic patients.
AB  - OBJECTIVE: Oxidative stress is a major contributing factor in the development of
      diabetic nephropathy. Peroxisome proliferator-activated receptor gamma
      heterozygous mice and Pro12Ala polymorphism in PPARG exhibited increased
      resistance to oxidative stress. Smoking increases the production of reactive
      oxygen species, which accelerates oxidative stress under hyperglycemia. To
      determine whether the Pro12Ala polymorphism, alone or in combination with
      smoking, contributes to the development of diabetic nephropathy, a case-control
      study was performed in 760 Chinese patients with type 2 diabetes. RESEARCH DESIGN
      AND METHODS: Among patients, 532 had diabetic nephropathy with microalbuminuria
      (n = 245) or overt albuminuria (n = 287), and 228 did not show either of these
      symptoms but had had diabetes for > or =10 years and were not undergoing anti
      hypertension treatment. RESULTS: After adjustment for confounders, the Pro/Pro
      genotype was significantly associated with diabetic nephropathy (odds ratio 2.30
      [95% CI 1.18-4.45], P = 0.014); smoking was also an independent risk factor for
      diabetic nephropathy (1.99 [1.08-3.68], P = 0.029). In addition, we identified
      possible synergistic effects; i.e., the high-risk group (smokers with the Pro/Pro
      genotype) showed 4.52 times higher risk (1.78-11.48, P = 0.002) of diabetic
      nephropathy than the low-risk group (nonsmokers with the Pro/Ala genotype) in a
      multiple logistic regression analysis controlled for the confounders.
      CONCLUSIONS: Our results indicated that the Pro/Pro genotype and smoking were
      significant independent risk factors for diabetic nephropathy. The possible
      synergistic effects of genotype and smoking may aggravate oxidative stress and
      contribute to the development of diabetic nephropathy.

PMID- 19837788
TI  - Capture of type 1 diabetes-susceptible HLA DR-DQ haplotypes in Japanese subjects
      using a tag single nucleotide polymorphism.
AB  - OBJECTIVE: To identify type 1 diabetes-susceptible HLA DR-DQ haplotypes using tag
      single nucleotide polymorphisms (SNPs) and to estimate the disease risk using
      these tag SNPs. RESEARCH DESIGN AND METHODS: Five tag SNPs were typed in a total
      of 211 Japanese subjects including 201 patients with type 1 diabetes who had
      already been typed for HLA-DRB1, -DQA1, and -DQB1 alleles and 300 control
      subjects. RESULTS: Tag SNP rs2395185 captured haplotypes involving all DR4
      specificities and DR9 specificity with a sensitivity of 98.5% and specificity of
      94.9%. Using the T allele of rs2395185, we obtained an odds ratio (95% CI) of
      2.87 (2.21-3.74) for type 1 diabetes. In addition, rs3129888 captured haplotypes
      involving HLA-DRB1*0802 with a sensitivity of 92.3% and specificity of 98.9%.
      CONCLUSIONS: Typing of two tag SNPs (rs2395185 and rs3129888) may be useful for
      the screening of Japanese subjects at genetic risk of type 1 diabetes.

PMID- 19837789
TI  - Serum levels of the adipokine chemerin in relation to renal function.
AB  - OBJECTIVE: To investigate serum levels of the adipokine chemerin in patients on
      chronic hemodialysis (CD) as compared with control patients with a glomerular
      filtration rate (GFR) >50 ml/min. RESEARCH DESIGN AND METHODS: Chemerin was
      quantified by ELISA in control patients (n = 60) and CD patients (n = 60) and
      correlated with clinical and biochemical measures of renal function, glucose, and
      lipid metabolism, as well as inflammation, in both groups. RESULTS: Median serum
      chemerin levels were more than twofold higher in CD patients (542.2 microg/l)
      compared with subjects with a GFR >50 ml/min (254.3 microg/l) (P < 0.001).
      Furthermore, GFR, as assessed by the original Modification of Diet in Renal
      Disease formula, independently predicted circulating chemerin concentrations in
      multiple regression analyses in both control patients (P < 0.05) and CD patients
      (P < 0.01). CONCLUSIONS: We demonstrate that markers of renal function are
      independently related to circulating chemerin levels.

PMID- 19837790
TI  - Gestational diabetes mellitus: NICE for the U.S.? A comparison of the American
      Diabetes Association and the American College of Obstetricians and Gynecologists
      guidelines with the U.K. National Institute for Health and Clinical Excellence
      guidelines.
AB  - OBJECTIVE: To compare recent U.S. and U.K. guidelines on gestational diabetes
      mellitus (GDM). RESEARCH DESIGN AND METHODS: The guidelines from the American
      Diabetes Association, the American College of Obstetricians and Gynecologists,
      and the National Institute for Health and Clinical Excellence (NICE) in the U.K.
      were collated and compared using a general inductive approach. RESULTS: There are
      substantial differences in the recommendations between the U.K. and the U.S.
      guidelines. Of particular note are the reduced sensitivities of the early and
      later antenatal and postnatal screening and diagnostic criteria. NICE undertook a
      cost-effectiveness analysis using lower prevalence estimates and limited outcomes
      and still showed screening for GDM to be cost-effective. CONCLUSIONS: The latest
      NICE recommendations appear to reduce access to proven, cost-effective management
      of GDM, an issue relevant in the current U.S. health care policy debate.

PMID- 19837791
TI  - Effectiveness of continuous glucose monitoring in a clinical care environment:
      evidence from the Juvenile Diabetes Research Foundation continuous glucose
      monitoring (JDRF-CGM) trial.
AB  - OBJECTIVE: To determine whether continuous glucose monitoring (CGM) is effective
      in the management of type 1 diabetes when implemented in a manner that more
      closely approximates clinical practice. RESEARCH DESIGN AND METHODS: After
      completion of a 6-month randomized controlled trial (RCT) evaluating CGM in
      children, adolescents, and adults with type 1 diabetes, CGM was initiated in the
      trial's control group with less intensive training and follow-up than was
      included in the RCT. Subjects had an outpatient training session, two follow-up
      phone calls, and outpatient visits at 1, 4, 13, and 26 weeks. For subjects with
      baseline A1C > or =7.0%, the primary outcome was change in A1C at 6 months.
      RESULTS: CGM use decreased from a median of 7.0 days/week in the first month in
      the > or =25-year-old group, 6.3 days/week in the 15-24 year olds, and 6.8
      days/week in the 8-14 year olds to 6.5, 3.3, and 3.7 days/week in the 6th month,
      respectively (P < 0.001 for each age-group). Among subjects with baseline A1C >
      or =7.0%, CGM use was associated with A1C reduction after 6 months (P = 0.02
      adjusted for age-group). Severe hypoglycemia decreased from 27.7 events per 100
      person-years in the 6-month control phase of the RCT to 15.0 events per 100
      person-years in the 6-month follow-up CGM phase (P = 0.08). CONCLUSIONS: Frequent
      use of CGM in a clinical care setting may improve A1C and reduce episodes of
      hypoglycemia. However, sustained frequent use of CGM is less likely in children
      and adolescents than in adults.

PMID- 19837792
TI  - A1C and diabetes diagnosis: The Rancho Bernardo Study.
AB  - OBJECTIVE: To examine the sensitivity and specificity of A1C as a diagnostic test
      for type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS: Cross-sectional
      study of community-dwelling adults without known diabetes who had an oral glucose
      tolerance test and A1C measured on the same day. RESULTS: Mean age of the 2,107
      participants was 69.4 +/- 11.1 years; 43% were men. Based on the American
      Diabetes Association (ADA) criteria, 198 had previously undiagnosed type 2
      diabetes. The sensitivity/specificity of A1C cut point of 6.5% was 44/79%.
      Results were similar in age- and sex-stratified analyses. Given the A1C cut point
      of 6.5%, 85% of participants were classified as nondiabetic by ADA criteria.
      CONCLUSIONS: The limited sensitivity of the A1C test may result in delayed
      diagnosis of type 2 diabetes, while the strict use of ADA criteria may fail to
      identify a high proportion of individuals with diabetes by A1C > or =6.5% or
      retinopathy.

PMID- 19837793
TI  - Visceral fat area and markers of insulin resistance in relation to colorectal
      neoplasia.
AB  - OBJECTIVE: Although abdominal obesity and related metabolic abnormalities are
      hypothesized to promote colorectal carcinogenesis, direct confirmation of this
      effect is required. Here, we examined the relation of early-stage colorectal
      neoplasia to visceral fat area and markers of insulin resistance. RESEARCH DESIGN
      AND METHODS: Subjects were participants in a comprehensive health screening
      conducted at the Hitachi Health Care Center, Ibaraki, Japan. During a 3-year
      period (2004-2007), a total of 108 patients with early-stage colorectal
      neoplasia, including 22 with early cancer, were identified among individuals who
      received both colorectal cancer screening and abdominal computed tomography
      scanning. Three control subjects matched to each case subject were randomly
      selected from those whose screening results were negative. Conditional logistic
      regression analysis was used to examine the association of measures of obesity
      and markers of insulin resistance with colorectal neoplasia, with adjustment for
      smoking and alcohol drinking. RESULTS: Visceral fat area, but not subcutaneous
      fat area, was significantly positively associated with colorectal cancer, with
      odds ratios (95% CI) for the lowest to highest tertile of visceral fat area of 1
      (reference), 2.17 (0.45-10.46), and 5.92 (1.22-28.65), respectively (P(trend) =
      0.02). Markers of insulin resistance, particularly fasting glucose, were also
      positively associated with colorectal cancer risk. In contrast, no associations
      were observed for colorectal adenomas. CONCLUSIONS: These results suggest that
      visceral adipose tissue accumulation and insulin resistance may promote the
      development of early-stage cancer but not adenoma in the colorectum.

PMID- 19837795
TI  - Insulin resistance in hyperthyroidism: the role of IL6 and TNF alpha.
AB  - OBJECTIVE: Although insulin resistance is a common finding in hyperthyroidism,
      the implicated mechanisms are obscure. The aim of this study was to investigate
      whether interleukin 6 (IL6) and tumour necrosis factor alpha (TNFalpha) are
      related to the development of insulin resistance in hyperthyroidism of
      nonautoimmune origin. DESIGN AND METHODS: A meal was given to ten hyperthyroid
      (HR) and ten euthyroid (EU) women. Plasma samples were taken for 360 min from the
      radial artery for measurements of glucose, insulin, and nonesterified fatty acids
      (NEFA). IL6 and TNFalpha were measured preprandially from the superficial
      epigastric vein and from the radial artery. RESULTS: i) In HR versus EU: (a)
      arterial glucose was similar (AUC(0-360) 2087+/-57 vs 2010+/-43 mM x min), but
      insulin was increased (AUC(0-360) 17 267+/-2447 vs 10 331+/-666 microU/ml x min,
      P=0.01), (b) homeostasis model assessment (HOMA) was increased (2.3+/-0.4 vs 1+/
      0.1 kg/m(2), P=0.007), (c) arterial NEFA were increased (AUC(0-360) 136+/-18 vs
      89+/-7 mmol/lxmin, P=0.03), (d) arterial IL6 (2+/-0.3 vs 0.9+/-0.1 pg/ml,
      P=0.0009) and TNFalpha (4.2+/-0.8 vs 1.5+/-0.2 pg/ml, P=0.003) were increased,
      and (e) IL6 production from the subcutaneous adipose tissue (AT) was increased
      (18+/-6 vs 5+/-1 pg/min per 100 ml tissue, P=0.04). ii) (a) Subcutaneous venous
      IL6 was positively associated with HOMA (beta-coefficient=1.7+/-0.7, P=0.049) and
      (b) although TNFalpha was not produced by the subcutaneous AT, arterial TNFalpha
      was positively associated with NEFA (AUC(0-360); beta-coefficient=0.045+/-0.01,
      P=0.005). CONCLUSIONS: In hyperthyroidism: i) glucose and lipid metabolism are
      resistant to insulin, ii) subcutaneous AT releases IL6, which could then act as
      an endocrine mediator of insulin resistance, iii) although there is no net
      secretion of TNFalpha by the subcutaneous AT, increased systemic TNFalpha levels
      may be related to the development of insulin resistance in lipolysis.

PMID- 19837794
TI  - Metabolic syndrome over 10 years and cognitive functioning in late midlife: the
      Whitehall II study.
AB  - OBJECTIVE: Evidence that the metabolic syndrome is a risk factor for poor
      cognition is mixed and is focused mainly on the elderly population; rarely is an
      adjustment made for socioeconomic factors. We examined this association in late
      midlife, with particular focus on cumulative effects and the role of
      socioeconomic circumstances. RESEARCH DESIGN AND METHODS: Analyses were performed
      for 4,150 white participants from the Whitehall II study. Metabolic syndrome,
      using the National Cholesterol Education Program Adult Treatment Panel III
      criteria, was assessed three times over the 10-year follow-up (1991-2001).
      Cognitive function was assessed using a battery of six tests at the end of the
      follow-up. RESULTS: After adjustment for demographic variables, health behaviors,
      and health status, participants with persistent metabolic syndrome (at least two
      of the three screenings) over the 10-year follow-up had lower cognitive
      performance than participants who never had metabolic syndrome. No significant
      differences in cognitive function were observed between participants with
      nonpersistent metabolic syndrome (one of the three screenings) and those who
      never had metabolic syndrome during the follow-up. Adjustment for adult
      occupational position attenuated this association by between 41 and 86%,
      depending on the measure of cognitive function. Adjustment for education had
      little effect. CONCLUSIONS: Only persistent metabolic syndrome was associated
      with lower cognitive performance in late midlife. Adult occupational position but
      not education had a substantial impact on this association; these results
      highlight the importance of adult socioeconomic circumstances in identifying and
      targeting risk factors for cognitive aging.

PMID- 19837796
TI  - Importance of trehalose biosynthesis for Sinorhizobium meliloti Osmotolerance and
      nodulation of Alfalfa roots.
AB  - The disaccharide trehalose is a well-known osmoprotectant, and trehalose
      accumulation through de novo biosynthesis is a common response of bacteria to
      abiotic stress. In this study, we have investigated the role of endogenous
      trehalose synthesis in the osmotolerance of Sinorhizobium meliloti. Genes coding
      for three possible trehalose synthesis pathways are present in the genome of S.
      meliloti 1021: OtsA, TreYZ, and TreS. Among these, OtsA has a major role in
      trehalose accumulation under all of the conditions tested and is the main system
      involved in osmoadaptation. Nevertheless, the other two systems are also
      important for growth in hyperosmotic medium. Genes for the three pathways are
      transcriptionally responsive to osmotic stress. The presence of at least one
      functional trehalose biosynthesis pathway is required for optimal competitiveness
      of S. meliloti to nodulate alfalfa roots.

PMID- 19837797
TI  - The InhA metalloproteases of Bacillus cereus contribute concomitantly to
      virulence.
AB  - The virulence of Bacillus cereus requires that bacteria have the capacity to
      colonize their host, degrade specific tissues, and circumvent the host immune
      system. To study this aspect of pathogenesis, we focused on three
      metalloproteases, InhA1, InhA2, and InhA3, which share more than 66% identity.
      The expression of these metalloprotease genes was assessed by transcriptional
      fusions with a lacZ reporter gene. The expression profiles suggest a
      complementary time course of InhA production. Indeed, the genes are
      simultaneously expressed but are oppositely controlled during stationary phase.
      We constructed single and multiple inhA mutants and assessed the bacterial
      locations of the proteins as well as their individual or additive roles in
      macrophage escape and toxicity, antibacterial-peptide cleavage, and virulence.
      InhA1, a major component of the spore exosporium, is the only InhA
      metalloprotease involved in bacterial escape from macrophages. A mutant lacking
      inhA1, inhA2, and inhA3 shows a strong decrease in the level of virulence for
      insects. Taken together, these results show that the InhA metalloproteases of B.
      cereus are important virulence factors that may allow the bacteria to counteract
      the host immune system.

PMID- 19837798
TI  - Diamide triggers mainly S Thiolations in the cytoplasmic proteomes of Bacillus
      subtilis and Staphylococcus aureus.
AB  - Glutathione constitutes a key player in the thiol redox buffer in many organisms.
      However, the gram-positive bacteria Bacillus subtilis and Staphylococcus aureus
      lack this low-molecular-weight thiol. Recently, we identified S-cysteinylated
      proteins in B. subtilis after treatment of cells with the disulfide-generating
      electrophile diamide. S cysteinylation is thought to protect protein thiols
      against irreversible oxidation to sulfinic and sulfonic acids. Here we show that
      S thiolation occurs also in S. aureus proteins after exposure to diamide. We
      further analyzed the formation of inter- and intramolecular disulfide bonds in
      cytoplasmic proteins using diagonal nonreducing/reducing sodium dodecyl sulfate
      gel electrophoresis. However, only a few proteins were identified that form inter
      or intramolecular disulfide bonds under control and diamide stress conditions in
      B. subtilis and S. aureus. Depletion of the cysteine pool was concomitantly
      measured in B. subtilis using a metabolomics approach. Thus, the majority of
      reversible thiol modifications that were previously detected by two-dimensional
      gel fluorescence-based thiol modification assay are most likely based on S
      thiolations. Finally, we found that a glutathione-producing B. subtilis strain
      which expresses the Listeria monocytogenes gshF gene did not show enhanced
      oxidative stress resistance compared to the wild type.

PMID- 19837800
TI  - Structural and genetic analysis of X-ray scattering by spores of Bacillus
      subtilis.
AB  - Dormant spores of Bacillus subtilis exhibit two prominent X-ray scattering peaks.
      These peaks persisted in spores lacking most alpha/beta-type small, acid-soluble
      protein or the CotE protein responsible for assembly of much spore coat protein,
      but they were absent from spores of strains lacking the late sporulation-specific
      transcription factor GerE.

PMID- 19837799
TI  - Outer membrane machinery and alginate synthesis regulators control membrane
      vesicle production in Pseudomonas aeruginosa.
AB  - The opportunistic human bacterial pathogen Pseudomonas aeruginosa produces
      membrane vesicles (MVs) in its surrounding environment. Several features of the
      P. aeruginosa MV production mechanism are still unknown. We previously observed
      that depletion of Opr86, which has a role in outer membrane protein (OMP)
      assembly, resulted in hypervesiculation. In this study, we showed that the outer
      membrane machinery and alginate synthesis regulatory machinery are closely
      related to MV production in P. aeruginosa. Depletion of Opr86 resulted in
      increased expression of the periplasmic serine protease MucD, suggesting that the
      accumulation of misfolded OMPs in the periplasm is related to MV production.
      Indeed, the mucD mutant showed a mucoid phenotype and the mucD mutation caused
      increased MV production. Strains with the gene encoding alginate synthetic
      regulator AlgU, MucA, or MucB deleted also caused altered MV production.
      Overexpression of either MucD or AlgW serine proteases resulted in decreased MV
      production, suggesting that proteases localized in the periplasm repress MV
      production in P. aeruginosa. Deletion of mucD resulted in increased MV proteins,
      even in strains with mutations in the Pseudomonas quinolone signal (PQS), which
      serves as a positive regulator of MV production. This study suggests that
      misfolded OMPs may be important for MV production, in addition to PQS, and that
      these regulators act in independent pathways.

PMID- 19837801
TI  - An SOS-regulated type 2 toxin-antitoxin system.
AB  - The Escherichia coli chromosome encodes seven demonstrated type 2 toxin-antitoxin
      (TA) systems: cassettes of two or three cotranscribed genes, one encoding a
      stable toxin protein that can cause cell stasis or death, another encoding a
      labile antitoxin protein, and sometimes a third regulatory protein. We
      demonstrate that the yafNO genes constitute an additional chromosomal type 2 TA
      system that is upregulated during the SOS DNA damage response. The yafNOP genes
      are part of the dinB operon, of which dinB underlies stress-induced mutagenesis
      mechanisms. yafN was identified as a putative antitoxin by homology to known
      antitoxins, implicating yafO (and/or yafP) as a putative toxin. Using phage
      mediated cotransduction assays for linkage disruption, we show first that yafN is
      an essential gene and second that it is essential only when yafO is present.
      Third, yafP is not a necessary part of either the toxin or the antitoxin. Fourth,
      although DinB is required, the yafNOP genes are not required for stress-induced
      mutagenesis in the Escherichia coli Lac assay. These results imply that yafN
      encodes an antitoxin that protects cells against a yafO-encoded toxin and show a
      protein-based TA system upregulated by the SOS response.

PMID- 19837805
TI  - National critical incident reporting: improving patient safety.

PMID- 19837802
TI  - Roles of the Bacillus anthracis spore protein ExsK in exosporium maturation and
      germination.
AB  - The Bacillus anthracis spore is the causative agent of the disease anthrax. The
      outermost structure of the B. anthracis spore, the exosporium, is a shell
      composed of approximately 20 proteins. The function of the exosporium remains
      poorly understood and is an area of active investigation. In this study, we
      analyzed the previously identified but uncharacterized exosporium protein ExsK.
      We found that, in contrast to other exosporium proteins, ExsK is present in at
      least two distinct locations, i.e., the spore surface as well as a more interior
      location underneath the exosporium. In spores that lack the exosporium basal
      layer protein ExsFA/BxpB, ExsK fails to encircle the spore and instead is present
      at only one spore pole, indicating that ExsK assembly to the spore is partially
      dependent on ExsFA/BxpB. In spores lacking the exosporium surface protein BclA,
      ExsK fails to mature into high-molecular-mass species observed in wild-type
      spores. These data suggest that the assembly and maturation of ExsK within the
      exosporium are dependent on ExsFA/BxpB and BclA. We also found that ExsK is not
      required for virulence in murine and guinea pig models but that it does inhibit
      germination. Based on these data, we propose a revised model of exosporium
      maturation and assembly and suggest a novel role for the exosporium in
      germination.

PMID- 19837803
TI  - Polyphosphate accumulation in Escherichia coli in response to defects in DNA
      metabolism.
AB  - Phenol-chloroform extraction of [(32)P]orthophosphate-labeled Escherichia coli
      cells followed by alkaline gel electrophoresis revealed, besides the expected
      chromosomal DNA, two non-DNA species that we have identified as
      lipopolysaccharides and polyphosphates by using a combination of biochemical and
      genetic techniques. We used this serendipitously found straightforward protocol
      for direct polyphosphate detection to quantify polyphosphate levels in E. coli
      mutants with diverse defects in the DNA metabolism. We detected increased
      polyphosphate accumulation in the ligA, ligA recBCD, dut ung, and thyA mutants.
      Polyphosphate accumulation may thus be an indicator of general DNA stress.

PMID- 19837806
TI  - Efficacy and safety of different techniques of paravertebral block for analgesia
      after thoracotomy: a systematic review and metaregression.
AB  - Various techniques and drug regimes for thoracic paravertebral block (PVB) have
      been evaluated for post-thoracotomy analgesia, but there is no consensus on which
      technique or drug regime is best. We have systematically reviewed the efficacy
      and safety of different techniques for PVB. Our primary aim was to determine
      whether local anaesthetic (LA) dose influences the quality of analgesia from PVB.
      Secondary aims were to determine whether choice of LA agent, continuous infusion,
      adjuvants, pre-emptive PVB, or addition of patient-controlled opioids improve
      analgesia. Indirect comparisons between treatment arms of different trials were
      made using metaregression. Twenty-five trials suitable for metaregression were
      identified, with a total of 763 patients. The use of higher doses of bupivacaine
      (890-990 mg per 24 h compared with 325-472.5 mg per 24 h) was found to predict
      lower pain scores at all time points up to 48 h after operation (P=0.006 at 8 h,
      P=0.001 at 24 h, and P<0.001 at 48 h). The effect-size estimates amount to around
      a 50% decrease in postoperative pain scores. Higher dose bupivacaine PVB was also
      predictive of faster recovery of pulmonary function by 72 h (effect-size estimate
      20.1% more improvement in FEV1, 95% CI 2.08%-38.07%, P=0.029). Continuous
      infusions of LA predicted lower pain scores compared with intermittent boluses
      (P=0.04 at 8 h, P=0.003 at 24 h, and P<0.001 at 48 h). The use of adjuvant
      clonidine or fentanyl, pre-emptive PVB, and the addition of patient-controlled
      opioids to PVB did not improve analgesia. Further well-designed trials of
      different PVB dosage and drug regimes are needed.

PMID- 19837807
TI  - Goal-directed haemodynamic therapy and gastrointestinal complications in major
      surgery: a meta-analysis of randomized controlled trials.
AB  - Postoperative gastrointestinal (GI) dysfunction is one of the most frequent
      complications in surgical patients. Most cases are associated with episodes of
      splanchnic hypoperfusion due to hypovolaemia or cardiac dysfunction. It has been
      suggested that perioperative haemodynamic goal-directed therapy (GDT) may reduce
      the incidence of these complications in cardiac surgery, and other surgery, but
      clear evidence is lacking. We have undertaken a meta-analysis of the effects of
      GDT on postoperative GI and liver complications. A systematic search, using
      MEDLINE, EMBASE, and The Cochrane Library databases, was performed. Sixteen
      randomized controlled trials (3410 participants) met the inclusion criteria. Data
      synthesis was obtained using odds ratio (OR) with 95% confidence interval (CI) by
      random-effects model. Statistical heterogeneity was assessed by Q and I2
      statistics. GI complications were ranked as major (required radiological or
      surgical intervention or life-threatening condition) or minor (no or only
      pharmacological treatment required). Major GI complications were significantly
      reduced by GDT when compared with a control group (OR, 0.42; 95% CI, 0.27-0.65).
      Minor GI complications were also significantly decreased in the GDT group (OR,
      0.29; 95% CI, 0.17-0.50). Treatment did not reduce hepatic injury rate (OR, 0.54;
      95% CI, 0.19-1.55). Quality sensitive analyses confirmed the main overall
      results. In patients undergoing major surgery, GDT, by maintaining an adequate
      systemic oxygenation, can protect organs particularly at risk of perioperative
      hypoperfusion and is effective in reducing GI complications.

PMID- 19837808
TI  - Sympathetic activity and cerebral oxygenation.

PMID- 19837809
TI  - Simulation and training in anaesthesia.

PMID- 19837810
TI  - One size does not fit all: proposed algorithm for ultrasonography in combination
      with nerve stimulation for peripheral nerve blockade.

PMID- 19837811
TI  - Anaesthetist's opinions on simulator-based training in continuing education.

PMID- 19837812
TI  - Kinking of a transluminal pacing probe.

PMID- 19837813
TI  - Convulsions associated with a low plasma level of local anaesthetics.

PMID- 19837814
TI  - Successful use of the laryngeal mask airway supreme in a patient with craneo
      cervical dystonia during magnetic resonance imaging.

PMID- 19837815
TI  - Supreme laryngeal mask airway for laparoscopic cholecystectomy in patient with
      severe pulmonary fibrosis.

PMID- 19837816
TI  - The phytochrome-interacting factor PIF7 negatively regulates DREB1 expression
      under circadian control in Arabidopsis.
AB  - Transcription factors of the DRE-Binding1 (DREB1)/C-repeat binding factor family
      specifically interact with a cis-acting dehydration-responsive element/C-repeat
      involved in low-temperature stress-responsive gene expression in Arabidopsis
      (Arabidopsis thaliana). Expression of DREB1s is induced by low temperatures and
      is regulated by the circadian clock under unstressed conditions. Promoter
      sequences of DREB1s contain six conserved motifs, boxes I to VI. We analyzed the
      promoter region of DREB1C using transgenic plants and found that box V with the G
      box sequence negatively regulates DREB1C expression under circadian control. The
      region around box VI contains positive regulatory elements for low-temperature
      induced expression of DREB1C. Using yeast one-hybrid screens, we isolated cDNA
      encoding the transcriptional factor Phytochrome-Interacting Factor7 (PIF7), which
      specifically binds to the G-box of the DREB1C promoter. The PIF7 gene was
      expressed in rosette leaves, and the PIF7 protein was localized in the nuclei of
      the cells. Transactivation experiments using Arabidopsis protoplasts indicated
      that PIF7 functions as a transcriptional repressor for DREB1C expression and that
      its activity is regulated by PIF7-interacting factors TIMING OF CAB EXPRESSION1
      and Phytochrome B, which are components of the circadian oscillator and the red
      light photoreceptor, respectively. Moreover, in the pif7 mutant, expression of
      DREB1B and DREB1C was not repressed under light conditions, indicating that PIF7
      functions as a transcriptional repressor for the expression of DREB1B and DREB1C
      under circadian control. This negative regulation of DREB1 expression may be
      important for avoiding plant growth retardation by the accumulation of DREB1
      proteins under unstressed conditions.

PMID- 19837817
TI  - Effect of Rubisco activase deficiency on the temperature response of CO2
      assimilation rate and Rubisco activation state: insights from transgenic tobacco
      with reduced amounts of Rubisco activase.
AB  - The activation of Rubisco in vivo requires the presence of the regulatory protein
      Rubisco activase. To elucidate its role in maintaining CO(2) assimilation rate at
      high temperature, we examined the temperature response of CO(2) assimilation rate
      at 380 microL L(-1) CO(2) concentration (A(380)) and Rubisco activation state in
      wild-type and transgenic tobacco (Nicotiana tabacum) with reduced Rubisco
      activase content grown at either 20 degrees C or 30 degrees C. Analyses of gas
      exchange and chlorophyll fluorescence showed that in the wild type, A(380) was
      limited by ribulose 1,5-bisphosphate regeneration at lower temperatures, whereas
      at higher temperatures, A(380) was limited by ribulose 1,5-bisphosphate
      carboxylation irrespective of growth temperatures. Growth temperature induced
      modest differences in Rubisco activation state that declined with measuring
      temperature, from mean values of 76% at 15 degrees C to 63% at 40 degrees C in
      wild-type plants. At measuring temperatures of 25 degrees C and below, an 80%
      reduction in Rubisco activase content was required before Rubisco activation
      state was decreased. Above 35 degrees C, Rubisco activation state decreased
      slightly with more modest decreases in Rubisco activase content, but the extent
      of the reductions in Rubisco activation state were small, such that a 55%
      reduction in Rubisco activase content did not alter the temperature sensitivity
      of Rubisco activation and had no effect on in vivo catalytic turnover rates of
      Rubisco. There was a strong correlation between Rubisco activase content and
      Rubisco activation state once Rubisco activase content was less that 20% of wild
      type at all measuring temperatures. We conclude that reduction in Rubisco
      activase content does not lead to an increase in the temperature sensitivity of
      Rubisco activation state in tobacco.

PMID- 19837818
TI  - Expression of the Arabidopsis mutant ABI1 gene alters abscisic acid sensitivity,
      stomatal development, and growth morphology in gray poplars.
AB  - The consequences of altered abscisic acid (ABA) sensitivity in gray poplar
      (Populus x canescens [Ait.] Sm.) development were examined by ectopic expression
      of the Arabidopsis (Arabidopsis thaliana) mutant abi1 (for abscisic acid
      insensitive1) gene. The expression resulted in an ABA-insensitive phenotype
      revealed by a strong tendency of abi1 poplars to wilt, impaired responsiveness of
      their stomata to ABA, and an ABA-resistant bud outgrowth. These plants therefore
      required cultivation under very humid conditions to prevent drought stress
      symptoms. Morphological alterations became evident when comparing abi1 poplars
      with poplars expressing Arabidopsis nonmutant ABI1 or wild-type plants. abi1
      poplars showed increased stomatal size, enhanced shoot growth, and retarded leaf
      and root development. The increased stomatal size and its reversion to the size
      of wild-type plants by exogenous ABA indicate a role for ABA in regulating
      stomatal development. Enhanced shoot growth and retarded leaf and root
      development support the hypothesis that ABA acts independently from drought
      stress as a negative regulator of growth in shoots and as a positive regulator of
      growth in leaves and roots. In shoots, we observed an interaction of ABA with
      ethylene: abi1 poplars exhibited elevated ethylene production, and the ethylene
      perception inhibitor Ag(+) antagonized the enhanced shoot growth. Thus, we
      provide evidence that ABA acts as negative regulator of shoot growth in
      nonstressed poplars by restricting ethylene production. Furthermore, we show that
      ABA has a role in regulating shoot branching by inhibiting lateral bud outgrowth.

PMID- 19837819
TI  - Specific domain structures control abscisic acid-, salicylic acid-, and stress
      mediated SIZ1 phenotypes.
AB  - SIZ1 (for yeast SAP and MIZ1) encodes the sole ortholog of mammalian PIAS (for
      protein inhibitor of activated STAT) and yeast SIZ SUMO (for small ubiquitin
      related modifier) E3 ligases in Arabidopsis (Arabidopsis thaliana). Four
      conserved motifs in SIZ1 include SAP (for scaffold attachment factor
      A/B/acinus/PIAS domain), PINIT (for proline-isoleucine-asparagine-isoleucine
      threonine), SP-RING (for SIZ/PIAS-RING), and SXS (for serine-X-serine, where X is
      any amino acid) motifs. SIZ1 contains, in addition, a PHD (for plant homeodomain)
      typical of plant PIAS proteins. We determined phenotypes of siz1-2 knockout
      mutants transformed with SIZ1 alleles carrying point mutations in the predicted
      domains. Domain SP-RING is required for SUMO conjugation activity and nuclear
      localization of SIZ1. Salicylic acid (SA) accumulation and SA-dependent
      phenotypes of siz1-2, such as diminished plant size, heightened innate immunity,
      and abscisic acid inhibition of cotyledon greening, as well as SA-independent
      basal thermotolerance were not complemented by the altered SP-RING allele of
      SIZ1. The SXS domain also controlled SA accumulation and was involved in greening
      and expansion of cotyledons of seedlings germinated in the presence of abscisic
      acid. Mutations of the PHD zinc finger domain and the PINIT motif affected in
      vivo SUMOylation. Expression of the PHD and/or PINIT domain mutant alleles of
      SIZ1 in siz1-2 promoted hypocotyl elongation in response to sugar and light. The
      various domains of SIZ1 make unique contributions to the plant's ability to cope
      with its environment.

PMID- 19837820
TI  - Determinants of exhaled nitric oxide in chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) has been reported to be associated with
      increased values of exhaled nitric oxide (ENO), which could not be entirely
      explained by the association between CRS and asthma. The aim of this study was to
      investigate the variables associated with increased ENO in patients with CRS.
      METHODS: This was a prospective cross-sectional descriptive study of 93
      consecutive patients with CRS. The effect on ENO of age, gender, atopy, asthma,
      respiratory symptoms without bronchial hyperresponsiveness (BHR), and nasal
      polyps was evaluated by multiple regression analysis. RESULTS: Nasal polyps (P =
      .01), asthma (P < .001), and respiratory symptoms without BHR (P = .01) were the
      only independent variables associated with increased ENO. The prevalence of
      asthma was significantly higher in subjects with nasal polyps (61% vs 29.4%), P =
      .005, whereas the prevalence of respiratory symptoms without BHR was higher in
      those without nasal polyps (44.1% vs 15.3%, P = .003). Respiratory symptoms
      without BHR were associated with significantly higher ENO and prevalence of
      sputum eosinophilia (eosinophils > 3%) in patients with nasal polyps compared
      with those without nasal polyps (68.2 vs 24.0 ppb, P = .001; 60% vs 8.3%, P =
      .03, respectively). CONCLUSIONS: The presence of nasal polyps in patients with
      CRS was associated with increased asthma prevalence as well as increased ENO
      levels. Respiratory symptoms without BHR were associated with eosinophilic airway
      inflammation and increased ENO only in patients with nasal polyps. These findings
      suggest important clinical and biologic differences between the two types of CRS,
      with and without nasal polyps.

PMID- 19837821
TI  - Pulmonary arterial hypertension: baseline characteristics from the REVEAL
      Registry.
AB  - BACKGROUND: The Registry to EValuate Early And Long-term pulmonary arterial
      hypertension disease management (REVEAL Registry) was established to provide
      updated characteristics of patients with pulmonary arterial hypertension (PAH)
      and to improve diagnosis, treatment, and management. METHODS: Fifty-four US
      centers enrolled consecutively screened patients with World Health Organization
      group I PAH who met expanded hemodynamic criteria of mean pulmonary arterial
      pressure (PAP) > 25 mm Hg at rest (30 mm Hg with exercise), pulmonary capillary
      wedge pressure (PCWP) <or= 18 mm Hg, and pulmonary vascular resistance >or= 240
      dynes x s x cm(-5). Patients meeting the traditional hemodynamic definition (PCWP
      <or= 15 mm Hg) were compared with those with a PCWP of 16 to 18 mm Hg. RESULTS:
      Between March 2006 and September 2007, 2,967 patients enrolled. Among 2,525
      adults meeting traditional hemodynamic criteria, the mean age was 53 +/- 14
      years, and 2,007 (79.5%) were women. The mean duration between symptom onset and
      diagnostic catheterization was 2.8 years, and 1,008 (41.3%) patients were treated
      with more than one pulmonary vascular-targeted medication. Compared with patients
      meeting the traditional hemodynamic definition of PAH, patients with a PCWP of 16
      to 18 mm Hg were older, more obese, had a lower 6-min walk distance, and had a
      higher incidence of systemic hypertension, sleep apnea, renal insufficiency, and
      diabetes. CONCLUSIONS: Patients in the REVEAL Registry are older and more often
      female than in previous descriptions. Delays between symptom onset and diagnostic
      catheterization persist. Many treatment regimens are fundamentally empirical, and
      data will be required to determine outcomes, improve risk stratification, and
      develop and validate more precise prognostic tools. Patients with PCWP of 16 to
      18 mm Hg differ in a number of important respects from those meeting the
      traditional hemodynamic definition of PAH.

PMID- 19837822
TI  - Serum IP-10 as a biomarker of human rhinovirus infection at exacerbation of COPD.
AB  - BACKGROUND: Human rhinovirus (HRV) is the most frequent virus associated with
      COPD exacerbations. Viral infections increase exacerbation severity and
      likelihood of hospitalization. As ease of sampling blood makes serum a more
      practical marker than sputum, we investigated whether changes in serum interferon
      gamma-inducible protein 10 (IP-10) from baseline to exacerbation were higher in
      airway HRV-positive exacerbations and whether IP-10 levels related to HRV load.
      METHODS: One hundred thirty-six patients with COPD and 70 controls were included
      over 2 years and 72 exacerbations sampled. HRV positivity and load were
      determined by reverse transcriptase-polymerase chain reaction in nasopharyngeal
      swabs and/or sputum at baseline and exacerbation. IP-10 was measured by enzyme
      linked immunosorbent assay in serum and compared with HRV load. RESULTS: At
      baseline, serum IP-10 was higher in patients with COPD than controls; medians
      were 149.4 pg/mL (103-215) and 111.7 pg/mL (82-178), P = .02. The presence of HRV
      at baseline did not increase IP-10: patients with COPD, 166.9 pg/mL (110-240) and
      149.4 pg/mL (103-215), P = .30; controls, 136.4 pg/mL (77-204) and 111.7 pg/mL
      (82-178), P = .53. IP-10 increased significantly from baseline to exacerbation in
      HRV-positive exacerbations: 154.9 pg/mL (114.0-195.1) to 207.5 pg/mL (142.1
      333.5), P = .009. There was no change in IP-10 between baseline and exacerbation
      in HRV-negative exacerbations: 168.3 pg/mL (94.3-249.8) and 175.6 pg/mL (107.2
      290.4), P = .49. At exacerbation, IP-10 correlated with sputum viral load: rho =
      0.48; P = .02. In receiver operating characteristics analysis, the combination of
      IP-10 and coryzal symptoms gave an area under the curve of 0.82 (95% CI, 0.74
      0.90). CONCLUSIONS: IP-10 increases from baseline to exacerbation in HRV-positive
      exacerbations and correlates with sputum HRV load. Serum IP-10 may be useful as a
      novel marker for these events.

PMID- 19837823
TI  - The COPD Helplessness Index: a new tool to measure factors affecting patient self
      management.
AB  - BACKGROUND: Psychologic factors affect how patients with COPD respond to attempts
      to improve their self-management skills. Learned helplessness may be one such
      factor, but there is no validated measure of helplessness in COPD. METHODS: We
      administered a new COPD Helplessness Index (CHI) to 1,202 patients with COPD.
      Concurrent validity was assessed through association of the CHI with established
      psychosocial measures and COPD severity. The association of helplessness with
      incident COPD exacerbations was then examined by following subjects over a median
      2.1 years, defining COPD exacerbations as COPD-related hospitalizations or ED
      visits. RESULTS: The CHI demonstrated internal consistency (Cronbach alpha =
      0.75); factor analysis was consistent with the CHI representing a single
      construct. Greater CHI-measured helplessness correlated with greater COPD
      severity assessed by the BODE (Body-mass, Obstruction, Dyspnea, Exercise) Index
      (r = 0.34; P < .001). Higher CHI scores were associated with worse generic (Short
      Form-12, Physical Component Summary Score) and respiratory-specific (Airways
      Questionnaire 20) health-related quality of life, greater depressive symptoms,
      and higher anxiety (all P < .001). Controlling for sociodemographics and smoking
      status, helplessness was prospectively associated with incident COPD
      exacerbations (hazard ratio = 1.31; P < .001). After also controlling for the
      BODE Index, helplessness remained predictive of COPD exacerbations among subjects
      with BODE Index </= median (hazard ratio = 1.35; P = .01), but not among subjects
      with higher BODE Index values (hazard ratio = 0.93; P = .34). CONCLUSIONS: The
      CHI is an internally consistent and valid measure, concurrently associated with
      health status and predictively associated with COPD exacerbations. The CHI may
      prove a useful tool in analyzing differential clinical responses mediated by
      patient-centered attributes.

PMID- 19837824
TI  - Asthma and serious psychological distress: prevalence and risk factors among US
      adults, 2001-2007.
AB  - BACKGROUND: For millions of adults, effective control of asthma requires a
      regimen of care that may be compromised by psychological factors, such as anxiety
      and depression. This study estimated the prevalence and risk factors for serious
      psychological distress (SPD) and explored their relationship to health-related
      quality of life (HRQOL) among adults with asthma in the United States. METHODS:
      We analyzed data from 186,738 adult respondents from the 2001-2007 US National
      Health Interview Survey. We calculated weighted average prevalence estimates of
      current asthma and SPD by demographic characteristics and health-related factors.
      We used logistic regression analysis to calculate odds ratios for factors that
      may have predicted asthma, SPD, and HRQOL. RESULTS: From 2001 to 2007, the
      average annual prevalence of current asthma was 7.0% and the average prevalence
      of SPD was 3.0%. Among adults with asthma, the prevalence of SPD was 7.5% (95%
      CI, 7.0%-8.1%). A negative association between HRQOL and SPD was found for all
      adults, independent of asthma status. A similar pattern of risk factors predicted
      SPD and the co-occurrence of SPD and asthma, although adults with asthma who
      reported lower socioeconomic status, a history of smoking or alcohol use, and
      more comorbid chronic conditions had significantly higher odds of SPD.
      CONCLUSION: This research suggests the importance of mental health screening for
      persons with asthma and the need for clinical and community-based interventions
      to target modifiable lifestyle factors that contribute to psychological distress
      and make asthma worse.

PMID- 19837825
TI  - Thrombocytopenia and thrombocytosis at time of hospitalization predict mortality
      in patients with community-acquired pneumonia.
AB  - BACKGROUND: Platelets are inflammatory cells with an important role in
      antimicrobial host defenses. We speculate that an abnormal platelet count may be
      a marker of severity in patients with community-acquired pneumonia (CAP). The
      objectives of this study were to evaluate if abnormal platelet count in
      hospitalized patients with CAP was associated with 30-day mortality and to
      compare platelet count and leukocyte count as predictors of 30-day mortality.
      METHODS: We performed a retrospective cohort study of 500 consecutive patients
      hospitalized with CAP at the Veterans Hospital of Louisville, Kentucky, between
      June 2001 and March 2006 to investigate the association of platelet count and
      leukocyte count with 30-day mortality. Predictor variables were platelet count
      and leukocyte count. Abnormal platelet count was < 100,000/L (thrombocytopenia)
      and > 400,000/L (thrombocytosis). The outcome variable was 30-day mortality. To
      control for potential confounding, a propensity score that incorporated 33
      variables was used. RESULTS: Platelet count was strongly associated (P = .0009)
      with 30-day mortality, whereas no association was observed for leukocyte count (P
      = .5114). High platelet counts resulted in a significantly increased risk of
      mortality. CONCLUSIONS: Thrombocytopenia and thrombocytosis are associated with
      mortality in patients hospitalized with CAP. When evaluating an initial CBC test
      in patients with CAP, an abnormal platelet count is a better predictor of outcome
      than an abnormal leukocyte count.

PMID- 19837826
TI  - Diagnosis of histoplasmosis by antigen detection in BAL fluid.
AB  - BACKGROUND: Detection of antigen in BAL is useful for diagnosis of
      histoplasmosis. The MVista Histoplasma antigen enzyme immunoassay has been
      modified to permit quantification. The purpose of this study is to compare the
      sensitivity of the quantitative antigen detection assay with cytopathology and
      culture of BAL specimens. METHODS: BAL from patients with histoplasmosis who were
      evaluated at the Indiana University Medical Center and controls without
      histoplasmosis were studied. BAL fluid was tested in the quantitative Histoplasma
      antigen assay. RESULTS: Antigen was detected in the BAL in 93.5% of patients with
      histoplasmosis, 80% with blastomycosis, and 0% of controls with nonfungal
      infections. Antigen was detected in the urine of 79% and serum in 65% of patients
      with histoplasmosis. Cytopathology was positive in 48% and culture in 48% of
      patients with histoplasmosis, and 40% and 60% of patients with blastomycosis,
      respectively. Serology was positive in 65%. Combining BAL antigen detection and
      BAL cytopathology, both methods for rapid diagnosis, the sensitivity was 96.8% in
      histoplasmosis and 80% in blastomycosis. CONCLUSIONS: Detection of antigen in BAL
      complements antigen detection in serum and urine as an objective diagnostic test
      for histoplasmosis.

PMID- 19837827
TI  - Long-term survival and quality of life after transfusion-associated pulmonary
      edema in critically ill medical patients.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion
      associated circulatory overload (TACO) commonly complicate transfusion in
      critically ill patients. Prior outcome studies of TACO and TRALI have focused on
      short-term morbidity and mortality, but the long-term survival and quality of
      life (QOL) of these patients remain unknown. METHODS: In a nested case-control
      study, we compared survival and QOL between critically ill medical patients who
      developed pulmonary edema after transfusion (TRALI or TACO) and medical
      critically ill transfused controls, matched by age, gender, and admission
      diagnostic group. QOL in survivors was assessed with a 36-item short form health
      survey 1 year after initial hospitalization. RESULTS: Hospital, 1-year, and 2
      year mortality among the 74 TRALI cases and 74 matched controls were 43.2% vs
      24.3% (P = .020), 63.8% vs 46.4% (P = .037) and 74.3% vs 54.3% (P = .031),
      whereas among the 51 TACO cases and 51 matched controls these values were 7.8% vs
      11.8% (P = .727), 38.0% vs 28.0% (P = .371), and 44.9% vs 38.8% (P = .512). When
      adjusted for age and baseline severity of illness in a Cox proportional hazard
      analysis, the development of TRALI remained associated with decreased survival
      (hazard ratio 1.86; 95% CI, 1.19-2.93; P = .006). Both TRALI (P = .006, P = .03)
      and TACO (P = .03, P = .049) were associated with prolonged ICU and hospital
      lengths of stay. CONCLUSIONS: In critically ill medical patients, development of
      TRALI, but not TACO, is independently associated with decreased long-term
      survival.

PMID- 19837828
TI  - N-methyl-D-aspartate glutamate receptor blockade attenuates lung injury
      associated with experimental sepsis.
AB  - BACKGROUND: The aim of this study was to examine the effects of the N-methyl-D
      aspartate receptor (NMDAR) channel blocker dizocilpine (MK-801) on lung injury in
      rats submitted to experimental sepsis induced by cecal ligation and perforation
      (CLP). METHODS: Adult male Wistar rats submitted to CLP were given a single
      systemic injection of MK-801 (subcutaneously at 0.3 mg/kg) administered 4 or 7 h
      after CLP induction. Twelve hours after CLP BAL was performed to determine total
      cell count, protein content, and inflammatory parameters. In addition, lung was
      excised for histopathologic analyses and determination of NMDAR subunits content.
      In a separate cohort of animals mortality was recorded for 5 days. RESULTS:
      Animals submitted to sepsis induced by CLP showed an increase in the content of
      NMDAR subunits NR1 and NR2A in the lung. Administration of MK-801 4 h after CLP
      induction resulted in a decrease in BAL fluid cellular content and decreased
      levels of proinflammatory cytokines. In addition, MK-801 decreased lung oxidative
      stress markers and histopathologic alterations and improved survival.
      CONCLUSIONS: These findings indicate that NMDAR blockade might represent a
      promising novel therapeutic strategy for the treatment of sepsis and inflammatory
      disorders.

PMID- 19837829
TI  - Determinants of postexercise heart rate recovery in patients with the obstructive
      sleep apnea syndrome.
AB  - BACKGROUND: Young patients with obstructive sleep apnea syndrome (OSAS) display
      an attenuated heart rate recovery (HRR) during the first minute (HRR-1) and the
      first 2 min (HRR-2) postexercise. We sought to compare determinants of HRR-1 and
      HRR-2 in OSAS and to assess whether these associations depend on age. METHODS:
      Exercise testing with measurements of HRR-1 and HRR-2 was performed in 54
      patients with untreated OSAS (median [interquartile range] apnea-hypopnea index
      27.5 [12.0-42.4] h(-1), desaturation index [DSI] 10.6 [5.1-25.0] h(-1)). RESULTS:
      Overall, higher DSI (P < .001) and higher total cholesterol ([TC] P = .02) were
      independent predictors of lower HRR-1, whereas lower peak heart rate (P < .001),
      higher resting heart rate (P = .006), and higher DSI (P = .01) were independently
      associated with lower HRR-2. In the below-median age group (age <or= 48 years; n
      = 27), higher DSI (P = .002) was the only independent predictor of lower HRR-1,
      and lower peak heart rate (P < .001) and higher DSI (P = .003) were independently
      associated with lower HRR-2. In contrast, in the above-median age group (age > 48
      years; n = 27) higher TC (P = .006), higher insulin resistance (P = .009), and
      higher resting heart rate (P = .048) were independently associated with lower HRR
      1, and lower estimated glomerular filtration rate (P = .001), higher resting
      heart rate (P = .002), higher TC (P = .005), and lower peak heart rate (P = .01)
      were independently associated with HRR-2. CONCLUSIONS: Assessment of HRR-2
      provides additional information on different aspects of OSAS compared with HRR-1.
      Markers of OSAS severity, such as DSI, are independently associated with HRR in
      younger patients only, whereas in older patients, HRR reflects OSAS-related
      metabolic and renal dysfunction.

PMID- 19837830
TI  - Importance of polyphosphate kinase 1 for Campylobacter jejuni viable-but
      nonculturable cell formation, natural transformation, and antimicrobial
      resistance.
AB  - Campylobacter jejuni, a gram-negative, microaerophilic bacterium, is a
      predominant cause of bacterial gastroenteritis in humans. Although considered
      fragile and fastidious and lacking many classical stress response mechanisms, C.
      jejuni exhibits a remarkable capacity for survival and adaptation, successfully
      infecting humans and persisting in the environment. Consequently, understanding
      the physiological and genetic properties that allow C. jejuni to survive and
      adapt to various stress conditions is crucial for therapeutic interventions. Of
      importance is polyphosphate (poly-P) kinase 1 (PPK1), which is a key enzyme
      mediating the synthesis of poly-P, an essential molecule for survival, mediating
      stress responses, host colonization, and virulence in many bacteria. Therefore,
      we investigated the role of PPK1 in C. jejuni pathogenesis, stress survival, and
      adaptation. Our findings demonstrate that a C. jejuni Deltappk1 mutant was
      deficient in poly-P accumulation, which was associated with a decreased ability
      to form viable-but-nonculturable cells under acid stress. The Deltappk1 mutant
      also showed a decreased frequency of natural transformation and an increased
      susceptibility to various antimicrobials. Furthermore, the Deltappk1 mutant was
      characterized by a dose-dependent deficiency in chicken colonization.
      Complementation of the Deltappk1 mutant with the wild-type copy of ppk1 restored
      the deficient phenotypes to levels similar to those of the wild type. Our results
      suggest that poly-P plays an important role in stress survival and adaptation and
      might contribute to genome plasticity and the spread and development of
      antimicrobial resistance in C. jejuni. These findings highlight the potential of
      PPK1 as a novel target for therapeutic interventions.

PMID- 19837831
TI  - Assessment of the total inflammatory potential of bioaerosols by using a
      granulocyte assay.
AB  - Occupational health symptoms related to bioaerosol exposure have been observed in
      a variety of working environments. Bioaerosols contain microorganisms and
      microbial components. The aim of this study was to estimate the total
      inflammatory potential (TIP) of bioaerosols using an in vitro assay based on
      granulocyte-like cells. A total of 129 bioaerosol samples were collected in the
      breathing zone of workers during their daily working routine at 22 biofuel
      plants. The samples were analyzed by traditional assays for dust, endotoxin,
      fungal spores, (1-->3)-beta-d-glucan, total number of bacteria, the enzyme N
      acetyl-beta-d-glucosaminidase (NAGase; primarily originating from fungi),
      Aspergillus fumigatus, and mesophilic and thermophilic actinomycetes; the samples
      were also assayed for TIP. In a multilinear regression four factors were
      significant for the TIP values obtained: endotoxin (P < 0.0001), fungal spores (P
      < 0.0001), (1-->3)-beta-d-glucan (P = 0.0005), and mesophilic actinomycetes (P =
      0.0063). Using this model to estimate TIP values on the basis of microbial
      composition, the correlation to the measured values was r = 0.91. When TIP values
      obtained in the granulocyte assay were related to the primary working area, we
      found that bioaerosol samples from personnel working in straw storage facilities
      showed high TIP values ( approximately 50 times the TIP of unstimulated
      controls). In contrast, bioaerosol samples from personnel with work functions in
      offices or laboratories showed low TIP values ( approximately 5 times the TIP of
      the unstimulated control). This indicates, as expected, that these areas were
      less contaminated. In conclusion, the granulocyte assay reacts to multiple
      contaminants in the environmental samples and can be used to obtain a measurement
      of TIP. Therefore, potential occupational health effects related to inflammation
      of the airways in a working environment can be estimated using this assay.

PMID- 19837832
TI  - Functional genomic analysis of two Staphylococcus aureus phages isolated from the
      dairy environment.
AB  - The genomes of the two lytic mutant Staphylococcus aureus bacteriophages, vB_SauS
      phiIPLA35 (phiIPLA35) and vB_SauS-phiIPLA88 (phiIPLA88), isolated from milk have
      been analyzed. Their genomes are 45,344 bp and 42,526 bp long, respectively, and
      contain 62 and 61 open reading frames (ORFS). Enzymatic analyses and sequencing
      revealed that the phiIPLA35 DNA molecule has 3'-protruding cohesive ends (cos) 10
      bp long, whereas phiIPLA88 DNA is 4.5% terminally redundant and most likely is
      packaged by a headful mechanism. N-terminal amino acid sequencing, mass
      spectrometry, bioinformatic analyses, and functional analyses enabled the
      assignment of putative functions to 58 gene products, including DNA packaging
      proteins, morphogenetic proteins, lysis components, and proteins necessary for
      DNA recombination, modification, and replication. Point mutations in their
      lysogeny control-associated genes explain their strictly lytic behavior.
      Muralytic activity associated with other structural components has been detected
      in virions of both phages. Comparative analysis of phiIPLA35 and phiIPLA88 genome
      structures shows that they resemble those of phi12 and phi11, respectively, both
      representatives of large genomic groupings within the S. aureus-infecting phages.

PMID- 19837833
TI  - Periplasmic electron transfer via the c-type cytochromes MtrA and FccA of
      Shewanella oneidensis MR-1.
AB  - Dissimilatory microbial reduction of insoluble Fe(III) oxides is a geochemically
      and ecologically important process which involves the transfer of cellular,
      respiratory electrons from the cytoplasmic membrane to insoluble, extracellular,
      mineral-phase electron acceptors. In this paper evidence is provided for the
      function of the periplasmic fumarate reductase FccA and the decaheme c-type
      cytochrome MtrA in periplasmic electron transfer reactions in the
      gammaproteobacterium Shewanella oneidensis. Both proteins are abundant in the
      periplasm of ferric citrate-reducing S. oneidensis cells. In vitro fumarate
      reductase FccA and c-type cytochrome MtrA were reduced by the cytoplasmic
      membrane-bound protein CymA. Electron transfer between CymA and MtrA was 1.4-fold
      faster than the CymA-catalyzed reduction of FccA. Further experiments showing a
      bidirectional electron transfer between FccA and MtrA provided evidence for an
      electron transfer network in the periplasmic space of S. oneidensis. Hence, FccA
      could function in both the electron transport to fumarate and via MtrA to mineral
      phase Fe(III). Growth experiments with a DeltafccA deletion mutant suggest a role
      of FccA as a transient electron storage protein.

PMID- 19837834
TI  - Analyses of current-generating mechanisms of Shewanella loihica PV-4 and
      Shewanella oneidensis MR-1 in microbial fuel cells.
AB  - Although members of the genus Shewanella have common features (e.g., the presence
      of decaheme c-type cytochromes [c-cyts]), they are widely variable in genetic and
      physiological features. The present study compared the current-generating ability
      of S. loihica PV-4 in microbial fuel cells (MFCs) with that of well-characterized
      S. oneidensis MR-1 and examined the roles of c-cyts in extracellular electron
      transfer. We found that strains PV-4 and MR-1 exhibited notable differences in
      current-generating mechanisms. While the MR-1 MFCs maintained a constant current
      density over time, the PV-4 MFCs continued to increase in current density and
      finally surpassed the MR-1 MFCs. Coulombic efficiencies reached 26% in the PV-4
      MFC but 16% in the MR-1 MFCs. Although both organisms produced quinone-like
      compounds, anode exchange experiments showed that anode-attached cells of PV-4
      produced sevenfold more current than planktonic cells in the same chamber, while
      planktonic cells of MR-1 produced twice the current of the anode-attached cells.
      Examination of the genome sequence indicated that PV-4 has more c-cyt genes in
      the metal reductase-containing locus than MR-1. Mutational analysis revealed that
      PV-4 relied predominantly on a homologue of the decaheme c-cyt MtrC in MR-1 for
      current generation, even though it also possesses two homologues of the decaheme
      c-cyt OmcA in MR-1. These results suggest that current generation in a PV-4 MFC
      is in large part accomplished by anode-attached cells, in which the MtrC
      homologue constitutes the main path of electrons toward the anode.

PMID- 19837835
TI  - Optimization of a rapid viability assay for Mycobacterium avium subsp.
      paratuberculosis by using alamarBlue.
AB  - A microtiter alamarBlue assay was adapted and optimized for Mycobacterium avium
      subsp. paratuberculosis. Using cell concentrations ranging from 10(4) to 10(8)
      CFU/ml, a minimum incubation time to indicate viability was obtained after 24 h.
      Rifampin (rifampicin) was used to demonstrate that this method has applications
      for high-throughput screening against M. avium subsp. paratuberculosis.

PMID- 19837836
TI  - Autoaggregation response of Fusobacterium nucleatum.
AB  - Fusobacterium nucleatum is a gram-negative oral bacterial species associated with
      periodontal disease progression. This species is perhaps best known for its
      ability to adhere to a vast array of other bacteria and eukaryotic cells.
      Numerous studies of F. nucleatum have examined various coaggregation partners and
      inhibitors, but it is largely unknown whether these interactions induce a
      particular genetic response. We tested coaggregation between F. nucleatum ATCC
      strain 25586 and various species of Streptococcus in the presence of a
      semidefined growth medium containing saliva. We found that this condition could
      support efficient coaggregation but, surprisingly, also stimulated a similar
      degree of autoaggregation. We further characterized the autoaggregation response,
      since few reports have examined this in F. nucleatum. After screening several
      common coaggregation inhibitors, we identified l-lysine as a competitive
      inhibitor of autoaggregation. We performed a microarray analysis of the
      planktonic versus autoaggregated cells and found nearly 100 genes that were
      affected after only about 60 min of aggregation. We tested a subset of these
      genes via real-time reverse transcription-PCR and confirmed the validity of the
      microarray results. Some of these genes were also found to be inducible in cell
      pellets created by centrifugation. Based upon these data, it appears that
      autoaggregation activates a genetic program that may be utilized for growth in a
      high cell density environment, such as the oral biofilm.

PMID- 19837837
TI  - Analysis of two gene clusters involved in the degradation of 4-fluorophenol by
      Arthrobacter sp. strain IF1.
AB  - Arthrobacter sp. strain IF1 is able to grow on 4-fluorophenol (4-FP) as a sole
      source of carbon and energy. To clone the 4-FP degradation genes, DNA libraries
      were constructed and screened with a probe obtained by PCR using primers designed
      on the basis of conserved regions of aromatic two-component monooxygenases.
      Sequencing of positive clones yielded two gene clusters, each harboring a gene
      encoding a monooxygenase with high sequence similarity to the oxygenase component
      of 4-nitrophenol and 4-chlorophenol monooxygenase systems. Both these
      monooxygenase genes were differentially expressed during growth on 4-FP, as
      revealed by Northern blotting and reverse transcription-PCR. One cluster also
      contained a gene for a flavin reductase. The monooxygenase and reductase were
      purified from Escherichia coli cells expressing the corresponding genes, and
      together they catalyzed NADH-dependent hydroxylation and dehalogenation of 4
      halophenols. The results indicate that strain IF1 transforms 4-FP to hydroquinone
      by a two-component monooxygenase system of which one component provides reduced
      flavin adenine dinucleotide at the expense of NADH and the other catalyzes para
      hydroxylation of 4-FP and other 4-substituted phenols.

PMID- 19837838
TI  - TetR-type transcriptional regulator VtpR functions as a global regulator in
      Vibrio tubiashii.
AB  - Vibrio tubiashii, a causative agent of severe shellfish larval disease, produces
      multiple extracellular proteins, including a metalloprotease (VtpA), as potential
      virulence factors. We previously reported that VtpA is toxic for Pacific oyster
      (Crassostrea gigas) larvae. In this study, we show that extracellular protease
      production by V. tubiashii was much reduced by elevated salt concentrations, as
      well as by elevated temperatures. In addition, V. tubiashii produced dramatically
      less protease in minimal salts medium supplemented with glucose or sucrose as the
      sole carbon source than with succinate. We identified a protein that belongs to
      the TetR family of transcriptional regulators, VtpR, which showed high homology
      with V. cholerae HapR. We conclude that VtpR activates VtpA production based on
      the following: (i) a VtpR-deficient V. tubiashii mutant did not produce
      extracellular proteases, (ii) the mutant showed reduced expression of a vtpA-lacZ
      fusion, and (iii) VtpR activated vtpA-lacZ in a V. cholerae heterologous
      background. Moreover, we show that VtpR activated the expression of an additional
      metalloprotease gene (vtpB). The deduced VtpB sequence showed high homology with
      a metalloprotease, VhpA, from V. harveyi. Furthermore, the vtpR mutant strain
      produced reduced levels of extracellular hemolysin, which is attributed to the
      lower expression of the V. tubiashii hemolysin genes (vthAB). The VtpR-deficient
      mutant also had negative effects on bacterial motility and did not demonstrate
      toxicity to oyster larvae. Together, these findings establish that the V.
      tubiashii VtpR protein functions as a global regulator controlling an array of
      potential virulence factors.

PMID- 19837839
TI  - In vivo display of a multisubunit enzyme complex on biogenic magnetic
      nanoparticles.
AB  - Magnetosomes are unique bacterial organelles comprising membrane-enveloped
      magnetic crystals produced by magnetotactic bacteria. Because of several
      desirable chemical and physical properties, magnetosomes would be ideal scaffolds
      on which to display highly complicated biological complexes artificially. As a
      model experiment for the functional expression of a multisubunit complex on
      magnetosomes, we examined the display of a chimeric bacterial RNase P enzyme
      composed of the protein subunit (C5) of Escherichia coli RNase P and the
      endogenous RNA subunit by expressing a translational fusion of C5 with MamC, a
      known magnetosome protein, in the magnetotactic bacterium Magnetospirillum
      gryphiswaldense. As intended, the purified C5 fusion magnetosomes, but not wild
      type magnetosomes, showed apparent RNase P activity and the association of a
      typical bacterial RNase P RNA. Our results demonstrate for the first time that
      magnetosomes can be employed as scaffolds for the display of multisubunit
      complexes.

PMID- 19837840
TI  - Reengineering Escherichia coli for Succinate Production in Mineral Salts Medium.
AB  - The fermentative metabolism of glucose was redirected to succinate as the primary
      product without mutating any genes encoding the native mixed-acid fermentation
      pathway or redox reactions. Two changes in peripheral pathways were together
      found to increase succinate yield fivefold: (i) increased expression of
      phosphoenolpyruvate carboxykinase and (ii) inactivation of the glucose
      phosphoenolpyruvate-dependent phosphotransferase system. These two changes
      increased net ATP production, increased the pool of phosphoenolpyruvate available
      for carboxylation, and increased succinate production. Modest further
      improvements in succinate yield were made by inactivating the pflB gene, encoding
      pyruvate formate lyase, resulting in an Escherichia coli pathway that is
      functionally similar to the native pathway in Actinobacillus succinogenes and
      other succinate-producing rumen bacteria.

PMID- 19837841
TI  - Genetic features of resident biofilms determine attachment of Listeria
      monocytogenes.
AB  - Planktonic Listeria monocytogenes cells in food-processing environments tend most
      frequently to adhere to solid surfaces. Under these conditions, they are likely
      to encounter resident biofilms rather than a raw solid surface. Although
      metabolic interactions between L. monocytogenes and resident microflora have been
      widely studied, little is known about the biofilm properties that influence the
      initial fixation of L. monocytogenes to the biofilm interface. To study these
      properties, we created a set of model resident Lactococcus lactis biofilms with
      various architectures, types of matrices, and individual cell surface properties.
      This was achieved using cell wall mutants that affect bacterial chain formation,
      exopolysaccharide (EPS) synthesis and surface hydrophobicity. The dynamics of the
      formation of these biofilm structures were analyzed in flow cell chambers using
      in situ time course confocal laser scanning microscopy imaging. All the L. lactis
      biofilms tested reduced the initial immobilization of L. monocytogenes compared
      to the glass substratum of the flow cell. Significant differences were seen in L.
      monocytogenes settlement as a function of the genetic background of resident
      lactococcal biofilm cells. In particular, biofilms of the L. lactis chain-forming
      mutant resulted in a marked increase in L. monocytogenes settlement, while
      biofilms of the EPS-secreting mutant efficiently prevented pathogen fixation.
      These results offer new insights into the role of resident biofilms in governing
      the settlement of pathogens on food chain surfaces and could be of relevance in
      the field of food safety controls.

PMID- 19837842
TI  - Degradation of a mixture of hydrocarbons, gasoline, and diesel oil additives by
      Rhodococcus aetherivorans and Rhodococcus wratislaviensis.
AB  - Two strains, identified as Rhodococcus wratislaviensis IFP 2016 and Rhodococcus
      aetherivorans IFP 2017, were isolated from a microbial consortium that degraded
      15 petroleum compounds or additives when provided in a mixture containing 16
      compounds (benzene, toluene, ethylbenzene, m-xylene, p-xylene, o-xylene, octane,
      hexadecane, 2,2,4-trimethylpentane [isooctane], cyclohexane, cyclohexanol,
      naphthalene, methyl tert-butyl ether [MTBE], ethyl tert-butyl ether [ETBE], tert
      butyl alcohol [TBA], and 2-ethylhexyl nitrate [2-EHN]). The strains had broad
      degradation capacities toward the compounds, including the more recalcitrant
      ones, MTBE, ETBE, isooctane, cyclohexane, and 2-EHN. R. wratislaviensis IFP 2016
      degraded and mineralized to different extents 11 of the compounds when provided
      individually, sometimes requiring 2,2,4,4,6,8,8-heptamethylnonane (HMN) as a
      cosolvent. R. aetherivorans IFP 2017 degraded a reduced spectrum of substrates.
      The coculture of the two strains degraded completely 13 compounds, isooctane and
      2-EHN were partially degraded (30% and 73%, respectively), and only TBA was not
      degraded. Significant MTBE and ETBE degradation rates, 14.3 and 116.1 mumol of
      ether degraded h(-1) g(-1) (dry weight), respectively, were measured for R.
      aetherivorans IFP 2017. The presence of benzene, toluene, ethylbenzene, and
      xylenes (BTEXs) had a detrimental effect on ETBE and MTBE biodegradation, whereas
      octane had a positive effect on the MTBE biodegradation by R. wratislaviensis IFP
      2016. BTEXs had either beneficial or detrimental effects on their own degradation
      by R. wratislaviensis IFP 2016. Potential genes involved in hydrocarbon
      degradation in the two strains were identified and partially sequenced.

PMID- 19837844
TI  - Development of a markerless genetic exchange system for Desulfovibrio vulgaris
      Hildenborough and its use in generating a strain with increased transformation
      efficiency.
AB  - In recent years, the genetic manipulation of the sulfate-reducing bacterium
      Desulfovibrio vulgaris Hildenborough has seen enormous progress. In spite of this
      progress, the current marker exchange deletion method does not allow for easy
      selection of multiple sequential gene deletions in a single strain because of the
      limited number of selectable markers available in D. vulgaris. To broaden the
      repertoire of genetic tools for manipulation, an in-frame, markerless deletion
      system has been developed. The counterselectable marker that makes this deletion
      system possible is the pyrimidine salvage enzyme, uracil
      phosphoribosyltransferase, encoded by upp. In wild-type D. vulgaris, growth was
      shown to be inhibited by the toxic pyrimidine analog 5-fluorouracil (5-FU),
      whereas a mutant bearing a deletion of the upp gene was resistant to 5-FU. When a
      plasmid containing the wild-type upp gene expressed constitutively from the
      aph(3')-II promoter (promoter for the kanamycin resistance gene in Tn5) was
      introduced into the upp deletion strain, sensitivity to 5-FU was restored. This
      observation allowed us to develop a two-step integration and excision strategy
      for the deletion of genes of interest. Since this in-frame deletion strategy does
      not retain an antibiotic cassette, multiple deletions can be generated in a
      single strain without the accumulation of genes conferring antibiotic
      resistances. We used this strategy to generate a deletion strain lacking the
      endonuclease (hsdR, DVU1703) of a type I restriction-modification system that we
      designated JW7035. The transformation efficiency of the JW7035 strain was found
      to be 100 to 1,000 times greater than that of the wild-type strain when stable
      plasmids were introduced via electroporation.

PMID- 19837843
TI  - Bacterial polyester inclusions engineered to display vaccine candidate antigens
      for use as a novel class of safe and efficient vaccine delivery agents.
AB  - Bioengineered bacterial polyester inclusions have the potential to be used as a
      vaccine delivery system. The biopolyester beads were engineered to display a
      fusion protein of the polyester synthase PhaC and the two key antigens involved
      in immune response to the infectious agent that causes tuberculosis,
      Mycobacterium tuberculosis, notably antigen 85A (Ag85A) and the 6-kDa early
      secreted antigenic target (ESAT-6) from Mycobacterium tuberculosis. Polyester
      beads displaying the respective fusion protein at a high density were
      successfully produced (henceforth called Ag85A-ESAT-6 beads) by recombinant
      Escherichia coli. The ability of the Ag85A-ESAT-6 beads to enhance mouse immunity
      to the displayed antigens was investigated. The beads were not toxic to the
      animals, as determined by weight gain and absence of lesions at the inoculation
      site in immunized animals. In vivo injection of the Ag85A-ESAT-6 beads in mice
      induced significant humoral and cell-mediated immune responses to both Ag85A and
      ESAT-6. Vaccination with Ag85A-ESAT-6 beads was efficient at stimulating immunity
      on their own, and this ability was enhanced by administration of the beads in an
      oil-in-water emulsion. In addition, vaccination with the Ag85A-ESAT-6 beads
      induced significantly stronger humoral and cell-mediated immune responses than
      vaccination with an equivalent dose of the fusion protein Ag85A-ESAT-6 alone. The
      immune response induced by the beads was of a mixed Th1/Th2 nature, as assessed
      from the induction of the cytokine gamma interferon (Th1 immune response) and
      increased levels of immunoglobulin G1 (Th2 immune response). Hence, engineered
      biopolyester beads displaying foreign antigens represent a new class of
      versatile, safe, and biocompatible vaccines.

PMID- 19837846
TI  - Microbial production of glyceric acid, an organic acid that can be mass produced
      from glycerol.
AB  - Glyceric acid (GA), an unfamiliar biotechnological product, is currently produced
      as a small by-product of dihydroxyacetone production from glycerol by
      Gluconobacter oxydans. We developed a method for the efficient biotechnological
      production of GA as a target compound for new surplus glycerol applications in
      the biodiesel and oleochemical industries. We investigated the ability of 162
      acetic acid bacterial strains to produce GA from glycerol and found that the
      patterns of productivity and enantiomeric GA compositions obtained from several
      strains differed significantly. The growth parameters of two different strain
      types, Gluconobacter frateurii NBRC103465 and Acetobacter tropicalis NBRC16470,
      were optimized using a jar fermentor. G. frateurii accumulated 136.5 g/liter of
      GA with a 72% d-GA enantiomeric excess (ee) in the culture broth, whereas A.
      tropicalis produced 101.8 g/liter of d-GA with a 99% ee. The 136.5 g/liter of
      glycerate in the culture broth was concentrated to 236.5 g/liter by desalting
      electrodialysis during the 140-min operating time, and then, from 50 ml of the
      concentrated solution, 9.35 g of GA calcium salt was obtained by crystallization.
      Gene disruption analysis using G. oxydans IFO12528 revealed that the membrane
      bound alcohol dehydrogenase (mADH)-encoding gene (adhA) is required for GA
      production, and purified mADH from G. oxydans IFO12528 catalyzed the oxidation of
      glycerol. These results strongly suggest that mADH is involved in GA production
      by acetic acid bacteria. We propose that GA is potentially mass producible from
      glycerol feedstock by a biotechnological process.

PMID- 19837847
TI  - Unveiling cell phenotypes in lung vascular remodeling.

PMID- 19837848
TI  - More life for a "terminal" cell.

PMID- 19837849
TI  - Inhaled nitric oxide improves lung structure and pulmonary hypertension in a
      model of bleomycin-induced bronchopulmonary dysplasia in neonatal rats.
AB  - Whether inhaled nitric oxide (iNO) prevents the development of bronchopulmonary
      dysplasia (BPD) in premature infants is controversial. In adult rats, bleomycin
      (Bleo) induces lung fibrosis and pulmonary hypertension, but the effects of Bleo
      on the developing lung and iNO treatment on Bleo-induced neonatal lung injury are
      uncertain. Therefore, we sought to determine whether early and prolonged iNO
      therapy attenuates changes of pulmonary vascular and alveolar structure in a
      model of BPD induced by Bleo treatment of neonatal rats. Sprague-Dawley rat pups
      were treated with Bleo (1 mg/kg ip daily) or vehicle (controls) from day 2 to 10,
      followed by recovery from day 11 to 19. Treatment groups received early (days 2
      10), late (days 11-19), or prolonged iNO therapy (10 ppm; days 2-19). We found
      that compared with controls, Bleo increased right ventricular hypertrophy (RVH),
      and pulmonary arterial wall thickness, and reduced vessel density
      alveolarization. In each iNO treatment group, iNO decreased RVH (P < 0.01) and
      wall thickness (P < 0.01) and restored vessel density after Bleo (P < 0.05). iNO
      therapy improved alveolarization for each treatment group after Bleo; however,
      the values remained abnormal compared with controls. Prolonged iNO treatment had
      greater effects on lung structure after bleomycin than late treatment alone. We
      conclude that Bleo induces lung structural changes that mimic BPD in neonatal
      rats, and that early and prolonged iNO therapy prevents right ventricle
      hypertrophy and pulmonary vascular remodeling and partially improves lung
      structure.

PMID- 19837845
TI  - Temporal and spatial diversity of the tap water microbiota in a Norwegian
      hospital.
AB  - We analyzed the temporal and spatial diversity of the microbiota in a low-usage
      and a high-usage hospital tap. We identified a tap-specific colonization pattern,
      with potential human pathogens being overrepresented in the low-usage tap. We
      propose that founder effects and local adaptation caused the tap-specific
      colonization patterns. Our conclusion is that tap-specific colonization
      represents a potential challenge for water safety.

PMID- 19837850
TI  - Viral aggregating and opsonizing activity in collectin trimers.
AB  - Collectins are collagenous lectins present in blood, respiratory lining fluid,
      and other mucosal secretions that play important roles in innate defense against
      infection. The collectin, surfactant protein D (SP-D), limits infection by
      viruses and bacteria in the respiratory tract, eye, and female genital tract.
      Multimeric SP-D has strong antiviral activity and is a potent viral and bacterial
      agglutinin and opsonin; however, trimers composed of the neck and carbohydrate
      recognition domain (hSP-D-NCRD) of SP-D lack these activities. We now show that,
      in contrast, a trimeric neck and CRD construct of bovine serum collectin CL-46
      induces aggregation of influenza A virus (IAV) and potently increases IAV uptake
      by neutrophils. CL-46-NCRD showed calcium-dependent and sugar-sensitive binding
      to both neutrophils and IAV. Replacement of specific residues of the CRD of human
      SP-D with those found in bovine serum collectins conferred opsonizing activity.
      The most effective substitution involved replacement of arginine 343 with valine
      (hSP-D-NCRD/R343V). hSP-D-NCRD/R343V greatly increased viral uptake by
      neutrophils and monocytes and also potentiated neutrophil respiratory burst
      responses. These effects were further increased by cross-linking of hSP-D
      NCRD/R343V trimers with MAbs directed against areas of the hSP-D-NCRD not
      involved in viral binding. Unlike the wild-type human SP-D hSP-D-NCRD, hSP-D
      NCRD/R343V also induced viral aggregation. These results indicate that collectins
      can act as opsonins for IAV even in the absence of the collagen domain or higher
      order multimerization. This may involve increased affinity of individual CRDs for
      glycoconjugates displayed on host cells or the viral envelope.

PMID- 19837851
TI  - Differential expression of platelet-activating factor acetylhydrolase in lung
      macrophages.
AB  - Platelet-activating factor (PAF) acetylhydrolase plays a crucial role
      inactivating the potent inflammatory mediator, PAF. PAF is implicated in the
      initiation and propagation of acute lung injury. Although PAF acetylhydrolase is
      a constitutively active plasma protein, increased PAF production during
      inflammatory events may necessitate an increase in PAF acetylhydrolase activity
      in the local environment. A series of experiments were conducted to determine
      whether the systemic administration of LPS to Sprague-Dawley rats resulted in
      enhanced expression of PAF acetylhydrolase in lung tissue. Ribonuclease
      protection assays revealed a dramatic increase in PAF acetylhydrolase mRNA, which
      peaked at 24 h following in vivo LPS administration. The increase in PAF
      acetylhydrolase mRNA was dose dependent and was detected when as little as 10
      microg/kg of LPS was administered. Western blot analyses of lung tissue
      homogenates confirmed an increased production of PAF acetylhydrolase protein in
      response to LPS. In addition, Western blot analyses revealed the rat PAF
      acetylhydrolase protein exhibited heterogeneous molecular weights with
      predominant species migrating at 63 and 67 kDa. Some of the molecular weight
      heterogeneity likely resulted from extensive glycosylation of the secreted
      protein. Immunohistochemical analyses of lung tissue sections and colocalization
      experiments revealed a heterogenous population of cells that express the plasma
      type PAF acetylhydrolase. Lung interstitial macrophages were PAF acetylhydrolase
      positive, but surprisingly, alveolar macrophages did not increase expression of
      PAF acetylhydrolase in response to systemic LPS administration. In addition, rat
      granulocytes consisting primarily of neutrophils were strongly positive for PAF
      acetylhydrolase in the LPS-exposed lung tissue. The absence of immunoreactive PAF
      acetylhydrolase in alveolar macrophages obtained from bronchial alveolar lavage
      confirmed that systemic LPS administration resulted in enhanced PAF
      acetylhydrolase expression only in a subset of lung macrophages.

PMID- 19837852
TI  - Sialyltransferases of marine bacteria efficiently utilize glycosphingolipid
      substrates.
AB  - Bacterial sialyltransferases (STs) from marine sources were characterized using
      glycosphingolipids (GSLs). Bacterial STs were found to be beta-galacotoside STs.
      There were two types of STs: (1) ST obtained from strains such as ishi-224,
      05JTC1 (#1), ishi-467, 05JTD2 (#2), and faj-16, 05JTE1 (#3), which form alpha2-3
      sialic acid (Sia) linkages, named alpha2-3ST, (2) ST obtained from strains such
      as ISH-224, N1C0 (#4), pda-rec, 05JTB2 (#5), and pda-0160, 05JTA2 (#6), which
      form alpha2-6 Sia linkages, named alpha2-6ST. All STs showed affinity to neolacto
      and lacto-series GSLs, particularly in neolactotetraosyl ceramide (nLc(4)Cer).
      No large differences were observed in the pH and temperature profiles of enzyme
      activities. Kinetic parameters obtained by Lineweaver-Burk plot analysis showed
      that #3 and #4 STs had practical synthetic activity and thus it became easily
      possible to achieve large-scale ganglioside synthesis (100-300 muM) using these
      recombinant enzymes. Gangliosides synthesized from nLc(4)Cer by alpha2-3 and
      alpha2-6STs were structurally characterized by several analytical and
      immunological methods, and they were identified as IV(3)alphaNeuAc-nLc(4)Cer(S2
      3PG) and IV(6)alphaNeuAc-nLc(4)Cer (S2-6PG), respectively. Further
      characterization of these STs using lactotetraosylceramide (Lc(4)Cer),
      neolactohexaosylceramide (i antigen), and IV(6)kladoLc(8)Cer (I antigen) showed
      the synthesis of corresponding gangliosides as well. Synthesized gangliosides
      showed binding activity to the influenza A virus [A/panama/2007/99 (H3N2)] at a
      similar level to purified S2-3PG and S2-6PG from mammalian sources. The above
      evidence suggests that these STs have unique features, including substrate
      specificities restricted to lacto- and neolactoseries GSLs, as well as catalytic
      potentials for ganglioside synthesis. This demonstrates that efficient in vitro
      ganglioside synthesis could be a valuable tool for selectively synthesizing Sias
      modifications, thereby permitting the exploration of unknown functions.

PMID- 19837853
TI  - Doublethinking our way to "scientific" legitimacy: the desiccation of human
      experience.
AB  - A multifaceted contemporary movement aims to correct alleged weaknesses in the
      scientific foundation of psychoanalysis. For both pragmatic-political and
      scientific reasons we are encouraged to do and/or study systematic empirical
      research on psychoanalytic process and outcome, as well as apparently relevant
      neuroscience. The thesis advanced here is that the privileged status this
      movement accords such research as against in-depth case studies is unwarranted
      epistemologically and is potentially damaging both to the development of our
      understanding of the analytic process itself and to the quality of our clinical
      work. In a nonobjectivist hermeneutic paradigm best suited to psychoanalysis, the
      analyst embraces the existential uncertainty that accompanies the realization
      that there are multiple good ways to be, in the moment and more generally in
      life, and that the choices he or she makes are always influenced by culture, by
      sociopolitical mind-set, by personal values, by countertransference, and by other
      factors in ways that are never fully known. Nevertheless, a critical,
      nonconformist psychoanalysis always strives to expose and challenge such
      foundations for the participants' choices. The "consequential uniqueness" of each
      interaction and the indeterminacy associated with the free will of the
      participants make the individual case study especially suited for the advancement
      of "knowledge"-that is, the progressive enrichment of sensibility-in our field.

PMID- 19837854
TI  - Introduction. Paper by William Meissner and a commentary by Leo Rangell.

PMID- 19837855
TI  - Volition and will in psychoanalysis.
AB  - To clarify the role and function of the will in psychoanalytic theory and praxis,
      the use and meaning of the concept of will are traced in the philosophical
      tradition influencing Freud, in Freud's own view of will, and in the subsequent
      history of psychoanalysis. Functions of the will relevant to psychoanalysis are
      described in terms of intellective preference and executive functioning.
      Operations of will as an executive function of the ego-self are analyzed,
      emphasizing will as efficient cause of motivated actions. The will functions to
      decide, choose, and initiate action directed to motivationally determined goals.
      The conclusion is drawn that will action is determined and directed by
      motivational influences, and that will decision and choice, while predominantly
      secondary process in organization, can operate consciously or unconsciously.
      Expressions of will action in psychopathology and in the analytic process are
      briefly discussed.

PMID- 19837856
TI  - The role of unconscious volition in psychoanalysis: commentary on Meissner.

PMID- 19837858
TI  - Selected posters from the 2008 poster session of the American Psychoanalytic
      Association.

PMID- 19837859
TI  - Termination. Panel report.

PMID- 19837860
TI  - Sex and shame: clinical dilemmas. Panel report.

PMID- 19837861
TI  - Bending the frame and judgment calls in everyday practice. Panel report.

PMID- 19837862
TI  - The role of dream work in contemporary psychoanalytic practice.

PMID- 19837863
TI  - Finding your way through chaos, fractals, and other exotic mathematical objects:
      a guide for the perplexed.

PMID- 19837864
TI  - Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional
      aspects in skeletal muscles of idiopathic inflammatory myopathies.
AB  - Idiopathic inflammatory myopathies (IIMs) are heterogeneous rheumatic disorders
      of unknown cause characterized by muscle weakness, inflammatory cell infiltrates,
      and major histocompatibility complex (MHC) class I expression on muscle fibers.
      The nonhistone nuclear protein alarmin high-mobility group box 1 protein (HMGB1)
      has been detected extranuclearly in muscle biopsies from patients with IIMs. We
      hypothesize that HMGB1 has a central role in the cause of muscle weakness,
      particularly in the early phases of IIMs. Experiments were performed on skeletal
      muscle fibers isolated from adult mice, which were exposed to recombinant
      interferon (IFN)-gamma or HMGB1. The myoplasmic free [Ca(2+)] was measured.
      Stimulation with IFN-gamma resulted in increased HMGB1 expression in muscle
      nuclei and the myoplasm. Exposure to HMGB1 induced a reversible up-regulation of
      MHC class I in the muscle fibers. However, HMGB1 exposure caused an irreversible
      decrease in Ca(2+) release from the sarcoplasmic reticulum during fatigue,
      induced by repeated tetanic contractions. HMGB1 and MHC class I were frequently
      colocalized in the myoplasm of muscle fibers in muscle biopsies from patients
      with early IIMs. However, HMGB1-expressing fibers outnumbered fibers expressing
      MHC class I. Our data indicate that HMGB1 could be an early inducer of skeletal
      muscle dysfunction in IIMs.

PMID- 19837865
TI  - Secretory granules in inositol 1,4,5-trisphosphate-dependent Ca2+ signaling in
      the cytoplasm of neuroendocrine cells.
AB  - Of all the intracellular organelles, secretory granules contain by far the
      highest calcium concentration; secretory granules of typical neuroendocrine
      chromaffin cells contain approximately 40 mM Ca(2+) and occupy approximately 20%
      cell volume, accounting for >60% of total cellular calcium. They also contain the
      majority of cellular inositol 1,4,5-trisphosphate receptors (IP(3)Rs) in addition
      to the presence of >2 mM of chromogranins A and B that function as high-capacity,
      low-affinity Ca(2+) storage proteins. Chromogranins A and B also interact with
      the IP(3)Rs and activate the IP(3)R/Ca(2+) channels. In experiments with both
      neuroendocrine PC12 and nonneuroendocrine NIH3T3 cells, in which the number of
      secretory granules present was changed by either suppression or induction of
      secretory granule formation, secretory granules were demonstrated to account for
      >70% of the IP(3)-induced Ca(2+) releases in the cytoplasm. Moreover, the IP(3)
      sensitivity of secretory granule IP(3)R/Ca(2+) channels is at least approximately
      6- to 7-fold more sensitive than those of the endoplasmic reticulum, thus
      enabling secretory granules to release Ca(2+) ahead of the endoplasmic reticulum.
      Further, there is a direct correlation between the number of secretory granules
      and the IP(3) sensitivity of cytoplasmic IP(3)R/Ca(2+) channels and the increased
      ratio of IP(3)-induced cytoplasmic Ca(2+) release, highlighting the importance of
      secretory granules in the IP(3)-dependent Ca(2+) signaling. Given that secretory
      granules are present in all secretory cells, these results presage critical roles
      of secretory granules in the control of cytoplasmic Ca(2+) concentrations in
      other secretory cells.-Yoo, S. H. Secretory granules in inositol 1,4,5
      trisphosphate-dependent Ca(2+) signaling in the cytoplasm of neuroendocrine
      cells.

PMID- 19837866
TI  - Central nervous system melanocortin-3 receptors are required for synchronizing
      metabolism during entrainment to restricted feeding during the light cycle.
AB  - Melanocortin-3 receptors (Mc3rs) in the central nervous system are involved in
      expression of anticipatory rhythms and synchronizing clocks maintaining circadian
      rhythms during restricted feeding (RF) [mice housed under a 12-h light-dark cycle
      with lights on between zeitgeber time (ZT) 0 to ZT12 fed 60% of normal calories
      between ZT7 and ZT11]. Because the systems governing circadian rhythms are
      important for adaptation to RF, we investigated whether Mc3rs are required for
      metabolic adaption to RF. Mc3r(-/-) mice subjected to RF exhibited normal weight
      loss; however, they developed hyperinsulinemia, glucose intolerance, increased
      expression of lipogenic genes, and increased ketogenesis relative to controls.
      Rhythmic expression of transcription factors regulating liver clock activity and
      energy metabolism (Bmal1, Rev-erbalpha, Pgc1, Foxo1, Hnf4alpha, and Pck1) was
      severely compromised in Mc3r(-/-) mice during RF. Inhibition of neural
      melanocortin receptors by agouti-related peptide also attenuated rhythmicity in
      the hepatic expression of these genes during RF. Collectively, these data suggest
      that neural Mc3rs are important for adapting metabolism and maintaining rhythms
      of liver metabolism during periods when feeding is restricted to the light cycle.
      Sutton, G. M., Begriche, K., Kumar, K. G., Gimble, J. M., Perez-Tilve, D.,
      Nogueiras, R., McMillan, R. P., Hulver, M. W., Tschop, M. H., Butler, A. A.
      Central nervous system melanocortin-3 receptors are required for synchronizing
      metabolism during entrainment to restricted feeding during the light cycle.

PMID- 19837868
TI  - Effects of intrauterine exposure to synthetic glucocorticoids on fetal, newborn,
      and infant hypothalamic-pituitary-adrenal axis function in humans: a systematic
      review.
AB  - BACKGROUND: Synthetic glucocorticoids are commonly used in reproductive medicine.
      Fetal organ systems are highly sensitive to changes in the intrauterine
      environment, including overexposure to glucocorticoids. Structural and functional
      alterations resulting from such changes may persist throughout life and have been
      associated with diverse diseases. One system that could be particularly sensitive
      to fetal glucocorticoid overexposure is the hypothalamic-pituitary-adrenal (hpa)
      axis. Many human studies have investigated this possibility, but a systematic
      review to identify consistent, emergent findings is lacking. METHODS: We
      systematically review 49 human studies, assessing the effects of intrauterine
      exposure to synthetic glucocorticoids on fetal, neonate, and infant hpa function.
      RESULTS: Study quality varied considerably, but the main findings held true after
      restricting the analyses to higher-quality studies: intrauterine exposure to
      synthetic glucocorticoids reduces offspring hpa activity under unstimulated
      conditions after pain but not pharmacological challenge. Although reduced
      unstimulated hpa function appears to recover within the first 2 wk postpartum,
      blunted hpa reactivity to pain is likely to persist throughout the first 4 months
      of life. There is some evidence that the magnitude of the effects is correlated
      with the total amount of glucocorticoids administered and varies with the time
      interval between glucocorticoid exposure and hpa assessment. CONCLUSIONS: This
      systematic review has allowed the demonstration of the way in which intrauterine
      exposure to various regimens of synthetic glucocorticoids affects various forms
      of hpa function. As such, it guides future studies in terms of which variables
      need to be focused on in order to further strengthen the understanding of such
      therapy, whilst continuing to profit from its clinical benefits.

PMID- 19837869
TI  - YABBYs and the transcriptional corepressors LEUNIG and LEUNIG_HOMOLOG maintain
      leaf polarity and meristem activity in Arabidopsis.
AB  - In Arabidopsis thaliana, FILAMENTOUS FLOWER (FIL) and YABBY3 (YAB3) encode YABBY
      domain proteins that regulate abaxial patterning, growth of lateral organs, and
      inflorescence phyllotaxy. In this study, we show that YABs physically interact
      with components of a transcriptional repressor complex that include LEUNIG (LUG),
      LEUNIG_HOMOLOG (LUH), the LUG-associated coregulator SEUSS, and related SEUSS
      LIKE proteins. Consistent with the formation of a LUG-YAB complex, we find that
      lug mutants enhance the polarity and growth defects of fil yab3 mutant leaves and
      that this enhancement is due to a loss of LUG activity from the abaxial domain.
      We performed a more extensive genetic analysis, which included the
      characterization of yab triple and quadruple mutants, lug luh/+ (heterozygous
      only for luh) mutants, and plants expressing artificial microRNAs targeting LUG
      or LUH. These analyses showed that the LUG-YAB complex also promotes adaxial cell
      identity in leaves as well as embryonic shoot apical meristem (SAM) initiation
      and postembryonic SAM maintenance. Based on the likely formation of the LUG-YAB
      complex in the abaxial domain of cotyledons and leaves, we propose that this
      complex has numerous non-cell-autonomous functions during plant development.

PMID- 19837871
TI  - Response to carbohydrate and fat refeeding in the expression of genes involved in
      nutrient partitioning and metabolism: striking effects on fibroblast growth
      factor-21 induction.
AB  - This study aimed to assess the effects of carbohydrate (CHO) and fat intake on
      the expression of key genes related with nutrient partitioning and metabolism in
      main tissues involved in energy metabolism (white adipose tissue, liver, and
      skeletal muscle). Rats were studied under different conditions: feeding state, 24
      h fasting, and 12 h refeeding after 24 h fasting with isocaloric amounts of CHO
      or fat. Fat, but not CHO, refeeding was associated with an increase in serum and
      liver triglyceride content. Main changes in gene expression elicited by CHO
      compared with fat refeeding were: 1) higher expression levels of genes related
      with lipogenesis (PPARgamma2, ChREBP, FAS), glucose uptake and metabolism (GLUT4,
      HKII), fatty acid uptake (LPL, CD36), and lipolysis (ATGL, HSL) in white adipose
      tissue; 2) higher expression levels of genes related with lipogenesis (FAS, SCD1)
      but lower ones related with fatty acid uptake (CD36) and oxidation (PPARalpha,
      CPT1, PDK4) in liver; and 3) higher expression levels of GLUT4 but lower ones
      related with fatty acid oxidation (PDK4 and UCP3) in muscle. It is worth
      mentioning that both CHO and fat refeeding resulted in a robust increase in both
      hepatic mRNA and circulating levels of fibroblast growth factor-21, compared with
      fasted levels. In summary, these results, showing marked differences in gene
      expression after CHO and fat refeeding, can explain diet-associated differences
      in fuel handling and partitioning between tissues; in addition, a role of
      fibroblast growth factor-21 in metabolic adaptations, not only in the ketotic
      state but also to face an unbalanced nutritional situation, is suggested.

PMID- 19837870
TI  - Functional analyses of LONELY GUY cytokinin-activating enzymes reveal the
      importance of the direct activation pathway in Arabidopsis.
AB  - Cytokinins play crucial roles in diverse aspects of plant growth and development.
      Spatiotemporal distribution of bioactive cytokinins is finely regulated by
      metabolic enzymes. LONELY GUY (LOG) was previously identified as a cytokinin
      activating enzyme that works in the direct activation pathway in rice (Oryza
      sativa) shoot meristems. In this work, nine Arabidopsis thaliana LOG genes (At
      LOG1 to LOG9) were predicted as homologs of rice LOG. Seven At LOGs, which are
      localized in the cytosol and nuclei, had enzymatic activities equivalent to that
      of rice LOG. Conditional overexpression of At LOGs in transgenic Arabidopsis
      reduced the content of N(6)-(Delta(2)-isopentenyl)adenine (iP) riboside 5'
      phosphates and increased the levels of iP and the glucosides. Multiple mutants of
      At LOGs showed a lower sensitivity to iP riboside in terms of lateral root
      formation and altered root and shoot morphology. Analyses of At LOG promoter:beta
      glucuronidase fusion genes revealed differential expression of LOGs in various
      tissues during plant development. Ectopic overexpression showed pleiotropic
      phenotypes, such as promotion of cell division in embryos and leaf vascular
      tissues, reduced apical dominance, and a delay of leaf senescence. Our results
      strongly suggest that the direct activation pathway via LOGs plays a pivotal role
      in regulating cytokinin activity during normal growth and development in
      Arabidopsis.

PMID- 19837867
TI  - Genetic regulation of pituitary gland development in human and mouse.
AB  - Normal hypothalamopituitary development is closely related to that of the
      forebrain and is dependent upon a complex genetic cascade of transcription
      factors and signaling molecules that may be either intrinsic or extrinsic to the
      developing Rathke's pouch. These factors dictate organ commitment, cell
      differentiation, and cell proliferation within the anterior pituitary.
      Abnormalities in these processes are associated with congenital hypopituitarism,
      a spectrum of disorders that includes syndromic disorders such as septo-optic
      dysplasia, combined pituitary hormone deficiencies, and isolated hormone
      deficiencies, of which the commonest is GH deficiency. The highly variable
      clinical phenotypes can now in part be explained due to research performed over
      the last 20 yr, based mainly on naturally occurring and transgenic animal models.
      Mutations in genes encoding both signaling molecules and transcription factors
      have been implicated in the etiology of hypopituitarism, with or without other
      syndromic features, in mice and humans. To date, mutations in known genes account
      for a small proportion of cases of hypopituitarism in humans. However, these
      mutations have led to a greater understanding of the genetic interactions that
      lead to normal pituitary development. This review attempts to describe the
      complexity of pituitary development in the rodent, with particular emphasis on
      those factors that, when mutated, are associated with hypopituitarism in humans.

PMID- 19837872
TI  - Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is
      regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced
      pancreatic beta-cell dysfunction.
AB  - Prostaglandin E(2) (PGE(2)) is a well-known mediator of beta-cell dysfunction in
      both type 1 and type 2 diabetes. We recently reported that down-regulation of the
      Akt pathway activity is implicated in PGE(2)-induced pancreatic beta-cell
      dysfunction. The aim of this study was to further dissect the signaling pathway
      of this process in pancreatic beta-cell line HIT-T15 cells and primary mouse
      islets. We found that PGE(2) time-dependently increased the c-Jun N-terminal
      kinase (JNK) pathway activity. JNK inhibition by the JNK-specific inhibitor
      SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS).
      PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear
      localization and transactivation of FOXO1. Activation of FOXO1 induced nuclear
      exclusion but had no obvious effect on the whole-cell protein level of pancreatic
      and duodenal homeobox 1 (PDX1). However, these effects were all attenuated by JNK
      inhibition. Furthermore, adenovirus-mediated overexpression of dominant-negative
      (DN)-FOXO1 abolished whereas constitutively active (CA)-FOXO1 mimicked the
      effects of PGE(2) on GSIS in isolated mouse islets. In addition, we demonstrated
      that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1
      luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed
      the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN
      JNK1 rescued PGE(2)-impaired GSIS in mouse islets. Our results revealed that
      activation of the JNK is involved in PGE(2)-induced beta-cell dysfunction. PGE(2)
      mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to
      nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally
      resulting in defective GSIS in pancreatic beta-cells.

PMID- 19837875
TI  - Expression of guanylyl cyclase (GC)-A and GC-B during brain development: evidence
      for a role of GC-B in perinatal neurogenesis.
AB  - Atrial (ANP) and C-type (CNP) natriuretic peptide generate physiological effects
      via selective activation of two closely related membrane receptors with guanylyl
      cyclase (GC) activity, known as GC-A and GC-B. As yet, however, the discrete
      roles for ANP/GC-A vs. CNP/GC-B signaling in many mammalian tissues are still
      poorly understood. We here used receptor affinity labeling and GC assays to
      characterize comparatively GC-A/GC-B expression and functional activity during
      rat brain development. The study revealed that GC-B predominates in the
      developing and GC-A in the adult brain, with regional differences each between
      cerebral cortex, cerebellum, and brain stem. Whereas GC-A levels nearly
      continuously increase between embryonal d 18 and adult, GC-B expression in brain
      is highest and widely distributed around postnatal d 1. The striking perinatal GC
      B peak coincides with elevated expression of nestin, a marker protein for neural
      stem/progenitor cells. Immunohistochemical investigations revealed a cell body
      restricted subcellular localization of GC-B and perinatal abundance of GC-B
      expressing cells in regions high in nestin-expressing cells. However, and
      supported by examination of nestin-GFP transgenic mice, GC-B and nestin are not
      coexpressed in the same cells. Rather, GC-B(+) cells are distinguished by
      expression of NeuN, an early marker of differentiating neurons. These findings
      suggest that GC-B(+) cells represent neuronal fate-specific progeny of nestin(+)
      progenitors and raise the attention to specific and pronounced activities of
      CNP/GC-B signaling during perinatal brain maturation. The absence of this
      activity may cause the neurological disorders observed in GC-B-deficient mice.

PMID- 19837874
TI  - Brain-endocrine interactions: a microvascular route in the mediobasal
      hypothalamus.
AB  - Blood-borne hormones acting in the mediobasal hypothalamus, like those
      controlling food intake, require relatively direct access to target chemosensory
      neurons of the arcuate nucleus (ARC). An anatomical substrate for this is a
      permeable microvasculature with fenestrated endothelial cells in the ARC, a
      system that has awaited comprehensive documentation. Here, the immunofluorescent
      detection of endothelial fenestral diaphragms in the rat ARC allowed us to
      quantitate permeable microvessels throughout its rostrocaudal extent. We have
      determined that permeable microvessels are part of the subependymal plexus
      irrigating exclusively the ventromedial (vm) ARC from the subadjacent
      neuroendocrine median eminence. Unexpectedly, permeable microvessels were
      concentrated proximal to the pituitary stalk. This marked topography strongly
      supports the functional importance of retrograde blood flow from the pituitary to
      the vmARC, therefore making a functional relationship between peripheral long
      loop, pituitary short-loop, and neuroendocrine ultra-short loop feedback,
      altogether converging for integration in the vmARC (formerly known as the
      hypophysiotrophic area), thereby so pivotal as a multicompetent brain
      endocrinostat.

PMID- 19837873
TI  - Androgens induce dopaminergic neurotoxicity via caspase-3-dependent activation of
      protein kinase Cdelta.
AB  - Aged men have a greater incidence of Parkinson's disease (PD) than women. PD is a
      neurodegenerative condition associated with the loss of dopamine neurons in the
      nigrostriatal pathway. This study examined the neurotoxic effects of androgens in
      a dopaminergic cell line (N27 cells) and the downstream signaling pathways
      activated by androgens. Treatment of N27 cells with testosterone- and
      dihydrotestosterone-induced mitochondrial dysfunction, protein kinase C (PKC)
      delta cleavage, and apoptosis in dopaminergic neuronal cells. Inhibition of
      caspase-3 prevented the cleavage of PKCdelta from the full-length element to the
      catalytic fragment and apoptosis in N27 cells, suggesting that androgen-induced
      apoptosis is mediated by caspase-3-dependent activation of PKCdelta. Androgen
      induced apoptosis may be specific to dopamine neurons as evidenced by a lack of
      testosterone-induced apoptosis in GnRH neurons. These results support a
      neurotoxic consequence of testosterone on dopaminergic neurons and may provide
      insight into the gender bias found in PD.

PMID- 19837876
TI  - Atrial natriuretic peptide promotes pancreatic islet beta-cell growth and
      Akt/Foxo1a/cyclin D2 signaling.
AB  - The adult differentiated insulin-secreting pancreatic islet beta-cell experiences
      slow growth. This study shows that atrial natriuretic peptide (ANP) stimulates
      cell proliferation and [(3)H]thymidine incorporation in INS-1E glucose-sensitive
      rat beta-cell line cells and isolated rat islet DNA. In addition, cGMP, the
      second messenger of natriuretic peptide receptors (NPR) A and B, stimulated islet
      DNA biosynthesis. The NPR-A receptor was expressed in INS-1E cells and islets.
      ANP-stimulated INS-1E cell DNA biosynthesis was blocked by preincubation with
      LY294002 (50 microM), an inhibitor of phosphatidylinositol 3'-kinase (PI3K). An
      indicator of cell cycle progression, cyclin D2 mRNA was increased by 2- to 3-fold
      in ANP- or 8-Br-cGMP-treated INS-1E cells and islets, and these responses were
      inhibited by LY294002. ANP and 8-Br-cGMP stimulated the phosphorylation of Akt
      and Foxo1a in INS-1E cells and islets, and LY294002 inhibited these responses. In
      contrast, ANP reduced the levels of phospho-ERK in INS-1E cells. Pancreas
      duodenum homeobox-1 (PDX-1) is essential for pancreas development, insulin
      production, and glucose homeostasis, and ANP increased PDX-1 mRNA levels by 2- to
      3-fold in INS-1E cells and islets. The levels of glucokinase mRNA in islets and
      INS-1E cells were also increased in response to ANP. The evidence suggests that
      pancreatic beta-cell NPR-A stimulation results in activation of a growth
      promoting signaling pathway that includes PI3K/Akt/Foxo1a/cyclin D2. These data
      support the conclusion that the activation of Akt by ANP or 8-Br-cGMP promotes
      cyclin D2, PDX-1, and glucokinase transcription by phosphorylating and
      restricting Foxo1a activity.

PMID- 19837878
TI  - Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and
      adipogenesis.
AB  - Insulin is a potent adipogenic hormone that triggers the induction of a series of
      transcription factors and specific proteins governing the differentiation of
      preadipocytes into mature adipocytes. Here we report that ubiquitin carboxyl
      terminal hydrolase (UCH)-L3, a deubiquitinating enzyme, promotes insulin
      signaling and adipogenesis. Uchl3(-/-) mice had less visceral white adipose
      tissue compared with wild-type mice. In vitro adipogenesis experiments revealed
      that mouse embryonic fibroblasts (MEFs) and preadipocytes from Uchl3(-/-) mice
      had impaired ability to differentiate into mature adipocytes than those from wild
      type mice. This difference was diminished by removing insulin from the medium. RT
      PCR analysis showed that insulin-regulated expression of srebp1c, fas, glut4, and
      adiponectin is impaired in Uchl3(-/-) cells. The phosphorylation of insulin/IGF-I
      receptor, Akt, glycogen synthase kinase-3beta, and FoxO1 was decreased in Uchl3(
      /-) MEFs treated with insulin. Moreover, ectopic expression of wild-type UCH-L3
      restored the phosphorylation of insulin/IGF-I receptor and adipocyte
      differentiation in Uchl3(-/-) MEFs. In contrast, hydrolase activity-deficient UCH
      L3 did not enhance insulin signaling and the expression of glut4, fabp4, and
      adiponectin, resulting in impaired formation of large lipid droplets. These
      results suggest that UCH-L3 promotes adipogenesis by enhancing insulin signaling
      in a hydrolase activity-dependent manner.

PMID- 19837877
TI  - Mechanisms involved in 3',5'-cyclic adenosine monophosphate-mediated inhibition
      of the ubiquitin-proteasome system in skeletal muscle.
AB  - Although it is well known that catecholamines inhibit skeletal muscle protein
      degradation, the molecular underlying mechanism remains unclear. This study was
      undertaken to investigate the role of beta(2)-adrenoceptors (AR) and cAMP in
      regulating the ubiquitin-proteasome system (UPS) in skeletal muscle. We report
      that increased levels of cAMP in isolated muscles, promoted by the cAMP
      phosphodiesterase inhibitor isobutylmethylxanthine was accompanied by decreased
      activity of the UPS, levels of ubiquitin-protein conjugates, and expression of
      atrogin-1, a key ubiquitin-protein ligase involved in muscle atrophy. In cultured
      myotubes, atrogin-1 induction after dexamethasone treatment was completely
      prevented by isobutylmethylxanthine. Furthermore, administration of clenbuterol,
      a selective beta(2)-agonist, to mice increased muscle cAMP levels and suppressed
      the fasting-induced expression of atrogin-1 and MuRF-1, atrogin-1 mRNA being much
      more responsive to clenbuterol. Moreover, clenbuterol increased the
      phosphorylation of muscle Akt and Foxo3a in fasted rats. Similar responses were
      observed in muscles exposed to dibutyryl-cAMP. The stimulatory effect of
      clenbuterol on cAMP and Akt was abolished in muscles from beta(2)-AR knockout
      mice. The suppressive effect of beta(2)-agonist on atrogin-1 was not mediated by
      PGC-1alpha (peroxisome proliferator-activated receptor-gamma coactivator 1alpha
      known to be induced by beta(2)-agonists and previously shown to inhibit atrogin-1
      expression), because food-deprived PGC-1alpha knockout mice were still sensitive
      to clenbuterol. These findings suggest that the cAMP increase induced by
      stimulation of beta(2)-AR in skeletal muscles from fasted mice is possibly the
      mechanism by which catecholamines suppress atrogin-1 and the UPS, this effect
      being mediated via phosphorylation of Akt and thus inactivation of Foxo3.

PMID- 19837879
TI  - The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and
      regulators of local blood flow.
AB  - Vertebrate red blood cells (RBCs) seem to serve tissue oxygen delivery in two
      distinct ways. Firstly, RBCs enable the adequate transport of O(2) between
      respiratory surfaces and metabolizing tissues by means of their high
      intracellular concentration of hemoglobin (Hb), appropriate allosteric
      interactions between Hb ligand-binding sites, and an adjustable intracellular
      chemical environment that allows fine-tuning of Hb O(2) affinity. Secondly, RBCs
      may sense tissue O(2) requirements via their degree of deoxygenation when they
      travel through the microcirculation and release vasodilatory compounds that
      enhance blood flow in hypoxic tissues. This latter function could be important in
      matching tissue O(2) delivery with local O(2) demand. Three main mechanisms by
      which RBCs can regulate their own distribution in the microcirculation have been
      proposed. These are: (1) deoxygenation-dependent release of ATP from RBCs, which
      stimulates production of nitric oxide (NO) and other vasodilators in the
      endothelium; (2) release of vasoactive NO from S-nitroso-Hb upon deoxygenation;
      and (3) reduction of naturally occurring nitrite to vasoactive NO by deoxygenated
      Hb. This Commentary inspects all three hypotheses with regard to their
      mechanisms, experimental evidence in their support and details that remain
      unresolved. The prime focus is on human/mammalian models, where most evidence for
      a role of erythrocyte ATP and NO release in blood flow regulation have
      accumulated. Information from other vertebrate groups is integrated in the
      analysis and used to discuss the evolutionary origin and general relevance of
      each hypothesis.

PMID- 19837880
TI  - Potential mechanism of sound production in Oreochromis niloticus (Cichlidae).
AB  - Although acoustic communication is an integral part of cichlid behaviour, its
      mechanism has never been identified before. In the present study, a combination
      of approaches was used to investigate the sound-producing mechanism of
      Oreochromis niloticus. Synchronisation of high-speed video data (500 frames s(
      1)) and cineradiographies (250 frames s(-1)) with the sound recordings made it
      possible to locate the different body parts involved in sound production in
      territorial males. Sounds are made during a backward movement of the pelvic and
      pectoral girdles and a forward movement of the second pterygiophore of the anal
      fin. Various electrostimulation experiments, dissections and observation of
      histological cross-sections revealed a set of bundles (that we call the vesica
      longitudinalis) situated in the hypaxial musculature, ventro-laterally to the
      swimbladder. Contraction of these bundles should result in compression of the rib
      cage and also of the swimbladder, because of its close association with the
      serosa and ribs. Deflation of the swimbladder resulted in a reduced sound
      intensity.

PMID- 19837881
TI  - Expression of calsequestrin in atrial and ventricular muscle of thermally
      acclimated rainbow trout.
AB  - Calsequestrin (CASQ) is the main Ca(2+) binding protein within the sarcoplasmic
      reticulum (SR) of the vertebrate heart. The contribution of SR Ca(2+) stores to
      contractile activation is larger in atrial than ventricular muscle, and in
      ectothermic fish hearts acclimation to low temperatures increases the use of SR
      Ca(2+) in excitation-contraction coupling. The hypotheses that chamber-specific
      and temperature-induced differences in SR function are due to the increased SR
      CASQ content were tested in rainbow trout (Oncorhynchus mykiss) acclimated at
      either 4 degrees C (cold acclimation, CA) or 18 degrees C (warm acclimation, WA).
      To this end, the trout cardiac CASQ (omCASQ2) was cloned and sequenced. The
      omCASQ2 consists of 1275 nucleotides encoding a predicted protein of 425 amino
      acids (54 kDa in molecular mass, MM) with a high (75-87%) sequence similarity to
      other vertebrate cardiac CASQs. The transcript levels of the omCASQ2 were 1.5-2
      times higher in CA than WA fish and about 2.5 times higher in the atrium than
      ventricle (P<0.001). The omCASQ2 protein was measured from western blots using a
      polyclonal antibody against the amino acid sequence 174-315 of the omCASQ2.
      Unlike the omCASQ2 transcripts, no differences were found in the abundance of the
      omCASQ2 protein between CA and WA fish, nor between the atrium and ventricle
      (P>0.05). However, a prominent qualitative difference appeared between the
      acclimation groups: two CASQ isoforms with apparent MMs of 54 and 59 kDa,
      respectively, were present in atrial and ventricular muscle of the WA trout
      whereas only the 54 kDa protein was clearly expressed in the CA heart. The 59 kDA
      isoform was a minor CASQ component representing 22% and 13% of the total CASQ
      proteins in the atrium and ventricle of the WA fish, respectively. In CA hearts,
      the 59 kDa protein was present in trace amounts (1.5-2.4%). Collectively, these
      findings indicate that temperature-related and chamber-specific differences in
      trout cardiac SR function are not related to the abundance of luminal Ca(2+)
      buffering by cardiac CASQ.

PMID- 19837882
TI  - Individual variation in rod absorbance spectra correlated with opsin gene
      polymorphism in sand goby (Pomatoschistus minutus).
AB  - Rod absorbance spectra, characterized by the wavelength of peak absorbance
      (lambda(max)) were related to the rod opsin sequences of individual sand gobies
      (Pomatoschistus minutus) from four allopatric populations [Adriatic Sea (A),
      English Channel (E), Swedish West Coast (S) and Baltic Sea (B)]. Rod lambda(max)
      differed between populations in a manner correlated with differences in the
      spectral light transmission of the respective water bodies [lambda(max): (A)
      approximately 503 nm; (E and S) approximately 505-506 nm; (B) approximately 508
      nm]. A distinguishing feature of B was the wide within-population variation of
      lambda(max) (505.6-511.3 nm). The rod opsin gene was sequenced in marked
      individuals whose rod absorbance spectra had been accurately measured.
      Substitutions were identified using EMBL/GenBank X62405 English sand goby
      sequence as reference and interpreted using two related rod pigments, the
      spectrally similar one of the Adriatic P. marmoratus (lambda(max) approximately
      507 nm) and the relatively red-shifted Baltic P. microps (lambda(max)
      approximately 515 nm) as outgroups. The opsin sequence of all E individuals was
      identical to that of the reference, whereas the S and B fish all had the
      substitution N151N/T or N151T. The B fish showed systematic within-population
      polymorphism, the sequence of individuals with lambda(max) at 505.6-507.5 nm were
      identical to S, but those with lambda(max) at 509-511.3 nm additionally had
      F261F/Y. The substitution F261Y is known to red-shift the rod pigment and was
      found in all P. microps. We propose that ambiguous selection pressures in the
      Baltic Sea and/or gene flow from the North Sea preserves polymorphism and is
      phenotypically evident as a wide variation in lambda(max).

PMID- 19837883
TI  - Ultrasound detection in the Gulf menhaden requires gas-filled bullae and an
      intact lateral line.
AB  - Clupeiform fish species, including the Gulf menhaden (Brevoortia patronus) that
      belong to the subfamily Alosinae, can detect ultrasound. Clupeiform fishes are
      unique in that they have specialized gas-filled bullae in the head associated
      with the ear via the bulla membrane and with the lateral line via the lateral
      recess membrane. It has been hypothesized that the utricle of the inner ear is
      responsible for ultrasound detection through a specialized connection to the gas
      filled bullae complex. Here, we show that the lateral line and its connection to
      the gas-filled bullae complex via the lateral recess are involved in ultrasound
      detection in Gulf menhaden. Removal of a small portion of the lateral line
      overlying the lateral recess membrane eliminates the ability of Gulf menhaden to
      detect ultrasound. We further show that the gas-filled bullae vibrates in
      response to ultrasound, that the gas-filled bullae are necessary for detecting
      ultrasound, and that the bullae connections to the lateral line via the lateral
      recess membrane play an important role in ultrasound detection. These results add
      a new dimension to the role of the lateral line and bullae as part of the
      ultrasonic detection system in Gulf menhaden.

PMID- 19837884
TI  - Energy metabolism and metabolic depression during exercise in Callinectes
      sapidus, the Atlantic blue crab: effects of the bacterial pathogen Vibrio
      campbellii.
AB  - Callinectes sapidus (Rathbun), the Atlantic blue crab, commonly harbors low to
      moderate amounts of bacteria in hemolymph and other tissues. These bacteria are
      typically dominated by Vibrio spp., which are known to cause mortality in the
      blue crab. The dose-dependent lethality of an isolate of Vibrio campbellii was
      determined in crabs; the mean 48 h LD(50) (half-maximal lethal dose) was 6.2 x
      10(5) colony forming units g(-1) crab. Injection of a sublethal dose of V.
      campbellii into the hemolymph of the crab resulted in a rapid and large
      depression (30-42%) of metabolic rate, which persisted for 24 h. Because gills
      are an organ of immune function as well as respiration, we were interested in how
      bacteria injected into the crab would affect the energetic costs associated with
      walking. Overall metabolism (aerobic and anaerobic) more than doubled in crabs
      walking for 30 min at 8 m min(-1). The metabolic depression resulting from
      bacterial injection persisted throughout the exercise period and patterns of
      phosphagen and adenylate consumption within walking leg muscle were not affected
      by treatment. The ability of crabs to supply required energy for walking is
      largely unaffected by exposure to Vibrio; however, Vibrio-injected crabs are less
      aerobic while doing so. This depressed metabolic condition in response to
      bacteria, present during moderate activity, could be a passive result of mounting
      an immune response or may indicate an actively regulated metabolic depression. A
      compromised metabolism can affect the performance of daily activities, such as
      feeding and predator avoidance or affect the ability to cope with environmental
      stressors, such as hypoxia.

PMID- 19837885
TI  - Ontogenetic changes in tracheal structure facilitate deep dives and cold water
      foraging in adult leatherback sea turtles.
AB  - Adult leatherbacks are large animals (300-500 kg), overlapping in size with
      marine pinniped and cetacean species. Unlike marine mammals, they start their
      aquatic life as 40-50 g hatchlings, so undergo a 10,000-fold increase in body
      mass during independent existence. Hatchlings are limited to the tropics and near
      surface water. Adults, obligate predators on gelatinous plankton, encounter cold
      water at depth (<1280 m) or high latitude and are gigantotherms that maintain
      elevated core body temperatures in cold water. This study shows that there are
      great ontogenetic changes in tracheal structure related to diving and exposure to
      cold. Hatchling leatherbacks have a conventional reptilian tracheal structure
      with circular cartilaginous rings interspersed with extensive connective tissue.
      The adult trachea is an almost continuous ellipsoidal cartilaginous tube composed
      of interlocking plates, and will collapse easily in the upper part of the water
      column during dives, thus avoiding pressure-related structural and physiological
      problems. It is lined with an extensive, dense erectile vascular plexus that will
      warm and humidify cold inspired air and possibly retain heat on expiration. A sub
      luminal lymphatic plexus is also present. Mammals and birds have independently
      evolved nasal turbinates to fulfil such a respiratory thermocontrol function; for
      them, turbinates are regarded as diagnostic of endothermy. This is the first
      demonstration of a turbinate equivalent in a living reptile.

PMID- 19837886
TI  - Insect eggs protected from high temperatures by limited homeothermy of plant
      leaves.
AB  - Virtually all aspects of insect biology are affected by body temperature, and
      many taxa have evolved sophisticated temperature-control mechanisms. All insects,
      however, begin life as eggs and lack the ability to thermoregulate. Eggs laid on
      leaves experience a thermal environment, and thus a body temperature, that is
      strongly influenced by the leaves themselves. Because plants can maintain leaf
      temperatures that differ from ambient, e.g. by evapotranspiration, plant hosts
      may protect eggs from extreme ambient temperatures. We examined the degree to
      which leaves buffer ambient thermal variation and whether that buffering benefits
      leaf-associated insect eggs. In particular, we: (1) measured temperature
      variation at oviposition sites in the field, (2) manipulated temperatures in the
      laboratory to determine the effect of different thermal conditions on embryo
      development time and survival, and (3) tested embryonic metabolic rates over
      increasing temperatures. Our results show that Datura wrightii leaves buffer
      Manduca sexta eggs from fatally high ambient temperatures in the southwestern
      USA. Moreover, small differences in temperature profiles among leaves can cause
      large variation in egg metabolic rate and development time. Specifically, large
      leaves were hotter than small leaves during the day, reaching temperatures that
      are stressfully high for eggs. This study provides the first mechanistic
      demonstration of how this type of leaf-constructed thermal refuge interacts with
      egg physiology.

PMID- 19837887
TI  - Limits to sustained energy intake. XI. A test of the heat dissipation limitation
      hypothesis in lactating Brandt's voles (Lasiopodomys brandtii).
AB  - The maximum rate of sustained energy intake (SusEI) may limit reproductive
      effort, thermoregulatory capability and other aspects of an animal's energy
      expenditure. Consequently, factors that limit SusEI are of interest. The ;heat
      dissipation limitation hypothesis' suggests that maximum SusEI during lactation
      is limited by the capacity to dissipate body heat generated as a by-product of
      processing food and producing milk. In the present study, we tested the heat
      dissipation limitation hypothesis in lactating Brandt's voles (Lasiopodomys
      brandtii). Female voles were mated and pregnant at 21(+/-1) degrees C. A random
      sample of animals was transferred into a hot room 30(+/-1) degrees C on the day
      of parturition. The energy intake of lactating voles at 30 degrees C was always
      lower than that at 21 degrees C. At peak lactation food intake was 3.3 g day(-1)
      lower at 30 degrees C than at 21 degrees C. There was no significant difference
      in digestibility. With similar mean litter sizes (7.26+/-0.46 pups at 21 degrees
      C and 7.78+/-0.39 pups at 30 degrees C at the beginning of parturition, 6.83+/
      0.51 pups at 21 degrees C and 7.73+/-0.50 pups at 30 degrees C at weaning), the
      milk energy output of mothers, evaluated from the difference between
      metabolizable energy intake and daily energy expenditure measured by doubly
      labelled water, at 30 degrees C was 23.3 kJ day(-1) lower than that at 21 degrees
      C on days 14-16 of lactation. As for reproductive performance, there was a
      difference in the response to the higher temperature between mothers raising
      large and those raising small litters. For small litters (<7) there was no
      significant change in litter mass, but for large litters (<or=7) there was a
      significant decrease at the higher temperature. On average, in larger litters the
      pups were 15.5 g heavier on day 12 of lactation when raised at 21 degrees C. Our
      data from Brandt's voles support the suggestion that SusEI at peak lactation is
      limited by heat dissipation capacity, particularly for those voles raising large
      litters. In smaller litters the peripheral limitation hypothesis may be more
      relevant. The importance of heat dissipation limits in species raising
      exclusively small litters needs to be investigated.

PMID- 19837888
TI  - White-throated sparrows calibrate their magnetic compass by polarized light cues
      during both autumn and spring migration.
AB  - The interaction and hierarchy of celestial and magnetic compass cues used by
      migratory songbirds for orientation has long been the topic of an intense debate.
      We have previously shown that migratory Savannah sparrows, Passerculus
      sandwichensis, use polarized light cues near the horizon at sunrise and sunset to
      recalibrate their magnetic compass. Birds exposed to a +/-90 deg. shifted
      artificial polarization pattern at sunrise or sunset recalibrated their magnetic
      compass, but only when given full access to celestial cues, including polarized
      light cues near the horizon. In the current study, we carried out cue conflict
      experiments with white-throated sparrows, Zonotrichia albicollis, during both
      spring and autumn migration in a transition zone between the species' breeding
      and wintering areas on the south shore of Lake Ontario. We show that white
      throated sparrows also recalibrate their magnetic compass by polarized light cues
      at sunrise and sunset. Sunrise exposure to an artificial polarization pattern
      shifted relative to the natural magnetic field or exposure to a shift of the
      magnetic field relative to the natural sky both led to recalibration of the
      magnetic compass, demonstrating that artificial polarizing filters do not create
      an anomalous, unnatural orientation response. Our results further indicate that
      there is no evidence for a difference in compass hierarchy between different
      phases of migration, confirming previous work showing that polarized light cues
      near the horizon at sunrise and sunset provide the primary calibration reference
      both in the beginning and at the end of migration.

PMID- 19837889
TI  - Radio frequency magnetic fields disrupt magnetoreception in American cockroach.
AB  - The sense that allows birds to orient themselves by the Earth's magnetic field
      can be disabled by an oscillating magnetic field whose intensity is just a
      fraction of the geomagnetic field intensity and whose oscillations fall into the
      medium or high frequency radio wave bands. This remarkable phenomenon points very
      clearly at one of two existing alternative magnetoreception mechanisms in
      terrestrial animals, i.e. the mechanism based on the radical pair reactions of
      specific photosensitive molecules. As the first such study in invertebrates, our
      work offers evidence that geomagnetic field reception in American cockroach is
      sensitive to a weak radio frequency field. Furthermore, we show that the
      'deafening' effect at Larmor frequency 1.2 MHz is stronger than at different
      frequencies. The parameter studied was the rise in locomotor activity of
      cockroaches induced by periodic changes in the geomagnetic North positions by 60
      deg. The onset of the disruptive effect of a 1.2 MHz field was found between 12
      nT and 18 nT whereas the threshold of a doubled frequency field 2.4 MHz fell
      between 18 nT and 44 nT. A 7 MHz field showed no impact even in maximal 44 nT
      magnetic flux density. The results indicate resonance effects rather than non
      specific bias of procedure itself and suggest that insects may be equipped with
      the same magnetoreception system as the birds.

PMID- 19837890
TI  - Waveform diversity of electric organ discharges: the role of electric organ auto
      excitability in Gymnotus spp.
AB  - This article shows that differences in the waveforms of the electric organ
      discharges (EODs) from two taxa are due to the different responsiveness of their
      electric organs (EOs) to their previous activity (auto-excitability). We compared
      Gymnotus omarorum endemic to Uruguay (35 degrees South, near a big estuary),
      which has four components in the head to tail electric field (V(1) to V(4)), with
      Gymnotus sp. endemic to the south of Brazil, Paraguay and Argentinean Mesopotamia
      (25 degrees South, inland), which shows a fifth component in addition to the
      others (V(5)). We found that: (a) the innervation pattern of the electrocytes,
      (b) the three earlier, neurally driven, EOD components (V(1) to V(3)), and (c)
      their remnants after curarisation were almost identical in the two taxa. The
      equivalent electromotive forces of late components (V(4) and V(5)) increased
      consistently as a function of the external current associated with the preceding
      component and were abolished by partial curarisation in both taxa. Taken together
      these data suggest that these components are originated in the responses of the
      electrocytes to longitudinal currents through the EO. By using a differential
      load procedure we showed that V(4) in G. omarorum responded to experimental
      changes in its excitation current with larger amplitude variations than V(4) in
      Gymnotus sp. We conclude that the differences in the EOD phenotype of the two
      studied taxa are due to the different EO auto-excitability. This, in turn, is
      caused either by the different expression of a genetic repertoire of conductance
      in the electrocyte membrane or in the wall of the tubes forming the EO.

PMID- 19837891
TI  - Kinematics of suction feeding in the seahorse Hippocampus reidi.
AB  - Fish typically use a rostro-caudal wave of head expansion to generate suction,
      which is assumed to cause a uni-directional, anterior-to-posterior flow of water
      in the expanding head. However, compared with typical fish, syngnathid fishes
      have a remarkably different morphology (elongated snout, small hyoid, immobile
      pectoral girdle) and feeding strategy (pivot feeding: bringing the small mouth
      rapidly close to the prey by neurocranial dorsorotation). As a result, it is
      unclear how suction is generated in Syngnathidae. In this study, lateral and
      ventral expansions of the head were quantified in Hippocampus reidi and linked to
      the kinematics of the mouth, hyoid and neurocranium. In addition, the flow
      velocities inside the bucco-pharyngeal cavity and in front of the mouth were
      calculated. Our data suggest that the volume changes caused by lateral expansion
      are dominant over ventral expansion. Maximum gape, neurocranium rotation and
      hyoid depression are all reached before actual volume increase and before visible
      prey movement. This implies that, unlike previously studied teleosts, hyoid
      rotation does not contribute to ventral expansion by lowering the floor of the
      mouth during prey capture in H. reidi. The lateral volume changes show a rostro
      caudal expansion, but the maximal flow velocity is not near the mouth aperture
      (as has been demonstrated for example in catfish) but at the narrow region of the
      buccal cavity, dorsal to the hyoid.

PMID- 19837892
TI  - Barnacle cement: a polymerization model based on evolutionary concepts.
AB  - Enzymes and biochemical mechanisms essential to survival are under extreme
      selective pressure and are highly conserved through evolutionary time. We applied
      this evolutionary concept to barnacle cement polymerization, a process critical
      to barnacle fitness that involves aggregation and cross-linking of proteins. The
      biochemical mechanisms of cement polymerization remain largely unknown. We
      hypothesized that this process is biochemically similar to blood clotting, a
      critical physiological response that is also based on aggregation and cross
      linking of proteins. Like key elements of vertebrate and invertebrate blood
      clotting, barnacle cement polymerization was shown to involve proteolytic
      activation of enzymes and structural precursors, transglutaminase cross-linking
      and assembly of fibrous proteins. Proteolytic activation of structural proteins
      maximizes the potential for bonding interactions with other proteins and with the
      surface. Transglutaminase cross-linking reinforces cement integrity. Remarkably,
      epitopes and sequences homologous to bovine trypsin and human transglutaminase
      were identified in barnacle cement with tandem mass spectrometry and/or western
      blotting. Akin to blood clotting, the peptides generated during proteolytic
      activation functioned as signal molecules, linking a molecular level event
      (protein aggregation) to a behavioral response (barnacle larval settlement). Our
      results draw attention to a highly conserved protein polymerization mechanism and
      shed light on a long-standing biochemical puzzle. We suggest that barnacle cement
      polymerization is a specialized form of wound healing. The polymerization
      mechanism common between barnacle cement and blood may be a theme for many marine
      animal glues.

PMID- 19837893
TI  - Whole limb kinematics are preferentially conserved over individual joint
      kinematics after peripheral nerve injury.
AB  - Biomechanics and neurophysiology studies suggest whole limb function to be an
      important locomotor control parameter. Inverted pendulum and mass-spring models
      greatly reduce the complexity of the legs and predict the dynamics of locomotion,
      but do not address how numerous limb elements are coordinated to achieve such
      simple behavior. As a first step, we hypothesized whole limb kinematics were of
      primary importance and would be preferentially conserved over individual joint
      kinematics after neuromuscular injury. We used a well-established peripheral
      nerve injury model of cat ankle extensor muscles to generate two experimental
      injury groups with a predictable time course of temporary paralysis followed by
      complete muscle self-reinnervation. Mean trajectories of individual joint
      kinematics were altered as a result of deficits after injury. By contrast, mean
      trajectories of limb orientation and limb length remained largely invariant
      across all animals, even with paralyzed ankle extensor muscles, suggesting
      changes in mean joint angles were coordinated as part of a long-term compensation
      strategy to minimize change in whole limb kinematics. Furthermore, at each
      measurement stage (pre-injury, paralytic and self-reinnervated) step-by-step
      variance of individual joint kinematics was always significantly greater than
      that of limb orientation. Our results suggest joint angle combinations are
      coordinated and selected to stabilize whole limb kinematics against short-term
      natural step-by-step deviations as well as long-term, pathological deviations
      created by injury. This may represent a fundamental compensation principle
      allowing animals to adapt to changing conditions with minimal effect on overall
      locomotor function.

PMID- 19837894
TI  - Topography of vision and behaviour.
AB  - Given the great range of visual systems, tasks and habitats, there is
      surprisingly little experimental evidence of how visual limitations affect
      behavioural strategies under natural conditions. Analysing this relationship will
      require an experimental system that allows for the synchronous measurement of
      visual cues and visually guided behaviour. The first step in quantifying visual
      cues from an animal's perspective is to understand the filter properties of its
      visual system. We examined the first stage of visual processing - sampling by the
      ommatidial array - in the compound eye of the fiddler crab Uca vomeris. Using an
      in vivo pseudopupil method we determined sizes and viewing directions of
      ommatidia and created a complete eye map of optical and sampling resolution
      across the visual field. Our results reveal five distinct eye regions (ventral,
      dorsal, frontal, lateral and medial) which exhibit clear differences in the
      organisation of the local sampling array, in particular with respect to the
      balance of resolution and contrast sensitivity. We argue that, under global eye
      space constraints, these regional optimisations reflect the information content
      and behavioural relevance of the corresponding parts of the visual field. In
      demonstrating the tight link between visual sampling, visual cues and behavioural
      strategies, our analysis highlights how the study of natural behaviour and
      natural stimuli is essential to our understanding and interpretation of the
      evolution and ecology of animal behaviour and the design of sensory systems.

PMID- 19837895
TI  - Auditory mechanics and sensitivity in the tropical butterfly Morpho peleides
      (Papilionoidea, Nymphalidae).
AB  - The ears of insects exhibit a broad functional diversity with the ability to
      detect sounds across a wide range of frequencies and intensities. In tympanal
      ears, the membrane is a crucial step in the transduction of the acoustic stimulus
      into a neural signal. The tropical butterfly Morpho peleides has an oval-shaped
      membrane at the base of the forewing with an unusual dome in the middle of the
      structure. We are testing the hypothesis that this unconventional anatomical
      arrangement determines the mechanical tuning properties of this butterfly ear.
      Using microscanning laser Doppler vibrometry to measure the vibrational
      characteristics of this novel tympanum, the membrane was found to vibrate in two
      distinct modes, depending on the frequency range: at lower frequencies (1-5 kHz)
      the vibration was focused at the proximal half of the posterior side of the outer
      membrane, while at higher frequencies (5-20 kHz) the entire membrane contributed
      to the vibration. The maximum deflection points of the two vibrational modes
      correspond to the locations of the associated chordotonal organs, suggesting that
      M. peleides has the capacity for frequency partitioning because of the different
      vibrational properties of the two membrane components. Extracellular nerve
      recordings confirm that the innervating chordotonal organs respond to the same
      frequency range of 1-20 kHz, and are most sensitive between 2 and 4 kHz, although
      distinct frequency discrimination was not observed. We suggest that this
      remarkable variation in structure is associated with function that provides a
      selective advantage, particularly in predator detection.

PMID- 19837896
TI  - Acoustical properties of the swimbladder in the oyster toadfish Opsanus tau.
AB  - Both the swimbladder and sonic muscles of the oyster toadfish Opsanus tau
      (Linnaeus) increase in size with fish growth making it difficult to distinguish
      their relative contributions to sound production. We examined acoustics of the
      swimbladder independent of the sonic muscles by striking it with a piezoelectric
      impact hammer. Amplitude and timing characteristics of bladder sound and
      displacement were compared for strikes of different amplitudes. Most of the first
      cycle of sound occurred during swimbladder compression, indicating that the
      bladder rapidly contracted and expanded as force increased during the strike.
      Harder hits were shorter in duration and generated a 30 dB increase in amplitude
      for a 5-fold or 14 dB range in displacement. For an equivalent strike dominant
      frequency, damping, bladder displacement and sound amplitude did not change with
      fish size, i.e. equal input generated equal output. The frequency spectrum was
      broad, and dominant frequency was driven by the strike and not the natural
      frequency of the bladder. Bladder displacement decayed rapidly (zeta averaged
      0.33, equivalent to an automobile shock absorber), and the bladder had a low Q
      (sharpness of tuning), averaging 1.8. Sound output of an acoustic source is
      determined by volume velocity (surface area x velocity), and bladder surface
      area, muscle dimensions and contraction amplitude increase with fish size.
      Therefore, larger fish will be capable of producing more intense sound. Because
      the bladder is a low Q resonator, its output will follow muscle contraction rates
      independent of its size and natural frequency.

PMID- 19837898
TI  - Allometry of skeletal muscle fine structure allows maintenance of aerobic
      capacity during ontogenetic growth.
AB  - Controversy exists over the scaling of oxygen consumption with body mass in
      vertebrates. A combination of biochemical and structural analyses were used to
      examine whether individual elements influencing oxygen delivery and demand within
      locomotory muscle respond similarly during ontogenetic growth of striped bass.
      Mass-specific metabolic enzyme activity confirmed that glycolytic capacity scaled
      positively in deep white muscle (regression slope, b=0.1 to 0.8) over a body mass
      range of approximately 20-1500 g, but only creatine phosphokinase showed positive
      scaling in lateral red muscle (b=0.5). Although oxidative enzymes showed negative
      allometry in red muscle (b=-0.01 to -0.02), mass-specific myoglobin content
      scaled positively (b=0.7). Capillary to fibre ratio of red muscle was higher in
      larger (1.42+/-0.15) than smaller (1.20+/-0.15) fish, suggesting progressive
      angiogenesis. By contrast, capillary density decreased (1989+/-161 vs 2,962+/-305
      mm(-2)) as a result of larger fibre size (658+/-31 vs 307+/-24 microm(2) in 1595
      g and 22.9 g fish, respectively). Thus, facilitated and convective delivery of
      O(2) show opposite allometric trends. Relative mitochondrial content of red
      muscle (an index of O(2) demand) varied little with body mass overall, but
      declined from approximately 40% fibre volume in the smallest to approximately 30%
      in the largest fish. However, total content per fibre increased, suggesting that
      mitochondrial biogenesis supported aerobic capacity during fibre growth.
      Heterogeneous fibre size indicates both hypertrophic and hyperplastic growth,
      although positive scaling of fibre myofibrillar content (b=0.085) may enhance
      specific force generation in larger fish. Modelling intracellular P(O(2))
      distribution suggests such integrated structural modifications are required to
      maintain adequate oxygen delivery (calculated P(O(2)) 5.15+/-0.02 kPa and 5.21+/
      0.01 kPa in small and large fish, respectively).

PMID- 19837897
TI  - Surgical removal of right-to-left cardiac shunt in the American alligator
      (Alligator mississippiensis) causes ventricular enlargement but does not alter
      apnoea or metabolism during diving.
AB  - Crocodilians have complete anatomical separation between the ventricles, similar
      to birds and mammals, but retain the dual aortic arch system found in all non
      avian reptiles. This cardiac anatomy allows surgical modification that prevents
      right-to-left (R-L) cardiac shunt. A R-L shunt is a bypass of the pulmonary
      circulation and recirculation of oxygen-poor blood back to the systemic
      circulation and has often been observed during the frequent apnoeic periods of
      non-avian reptiles, particularly during diving in aquatic species. We eliminated
      R-L shunt in American alligators (Alligator mississippiensis) by surgically
      occluding the left aorta (LAo; arising from right ventricle) upstream and
      downstream of the foramen of Panizza (FoP), and we tested the hypotheses that
      this removal of R-L shunt would cause afterload-induced cardiac remodelling and
      adversely affect diving performance. Occlusion of the LAo both upstream and
      downstream of the FoP for approximately 21 months caused a doubling of RV
      pressure and significant ventricular enlargement (average approximately 65%)
      compared with age-matched, sham-operated animals. In a separate group of
      recovered, surgically altered alligators allowed to dive freely in a dive chamber
      at 23 degrees C, occlusion of the LAo did not alter oxygen consumption or
      voluntary apnoeic periods relative to sham animals. While surgical removal of R-L
      shunt causes considerable changes in cardiac morphology similar to aortic banding
      in mammals, its removal does not affect the respiratory pattern or metabolism of
      alligators. It appears probable that the low metabolic rate of reptiles, rather
      than pulmonary circulatory bypass, allows for normal aerobic dives.

PMID- 19837899
TI  - Methionine supplementation influences melanin-based plumage colouration in
      Eurasian kestrel, Falco tinnunculus, nestlings.
AB  - The extent to which the expression of melanin-based plumage colouration in birds
      is genetically or environmentally determined is controversial. Here, we performed
      a between-nest design supplementation with either the sulphur amino acid dl
      methionine or with water to investigate the importance of the non-genetic
      component of melanin-based plumage colouration in the Eurasian kestrel, Falco
      tinnunculus. Methionine affects growth and immunity, thus we aimed to modify
      nestling growth and immunity before feather development. Then, we measured the
      effect of the experiment on colouration of two melanin-based plumage patches of
      nestling kestrels. We found that methionine slowed down nestling growth through
      treatment administration and that nestlings compensated by speeding up their
      growth later. We did not find any effects of methionine on nestling immunity
      (i.e. lymphocyte counts, natural antibody levels or complement-mediated
      immunity). Effects on growth seemed to be mirrored by changes in nestling
      colouration in the two sexes: methionine-nestlings showed less intense brown
      plumage on their backs compared with control nestlings. These results provide
      support for a non-genetic determination of a melanin-based plumage patch in the
      two sexes of nestling kestrels.

PMID- 19837900
TI  - Visual optics and ecomorphology of the growing shark eye: a comparison between
      deep and shallow water species.
AB  - Elasmobranch fishes utilise their vision as an important source of sensory
      information, and a range of visual adaptations have been shown to reflect the
      ecological diversity of this vertebrate group. This study investigates the
      hypotheses that visual optics can predict differences in habitat and behaviour
      and that visual optics change with ontogenetic growth of the eye to maintain
      optical performance. The study examines eye structure, pupillary movement,
      transmission properties of the ocular media, focal properties of the lens,
      tapetum structure and variations in optical performance with ontogenetic growth
      in two elasmobranch species: the carcharhinid sandbar shark, Carcharhinus
      plumbeus, inhabiting nearshore coastal waters, and the squalid shortspine
      spurdog, Squalus mitsukurii, inhabiting deeper waters of the continental shelf
      and slope. The optical properties appear to be well tuned for the visual needs of
      each species. Eyes continue to grow throughout life, resulting in an ontogenetic
      shift in the focal ratio of the eye. The eyes of C. plumbeus are optimised for
      vision under variable light conditions, which change during development as the
      animal probes new light environments in its search for food and mates. By
      contrast, the eyes of S. mitsukurii are specifically adapted to enhance retinal
      illumination within a dim light environment, and the detection of bioluminescent
      prey may be optimised with the use of lenticular short-wavelength-absorbing
      filters. Our findings suggest that the light environment strongly influences
      optical features in this class of vertebrates and that optical properties of the
      eye may be useful predictors of habitat and behaviour for lesser-known species of
      this vertebrate group.

PMID- 19837901
TI  - Deciphering the clinical spectrum of occupational rhinitis.

PMID- 19837902
TI  - An improved estimate of the quantitative relationship between polycyclic
      hydrocarbons and lung cancer.

PMID- 19837905
TI  - Ligand- and heterodimer-directed signaling of the CB(1) cannabinoid receptor.
AB  - Seven-transmembrane G protein-coupled receptors (GPCRs) represent the single
      largest family of cell surface receptors. Signaling through these receptors is
      controlled by changes in the conformation of the receptor from inactive to active
      conformations, which in turn lead to the activation of multiple downstream
      signaling pathways. To facilitate greater diversity in signaling responses, many
      of these receptors are capable of adopting several distinct active conformations,
      in which each couples preferentially to its own set of downstream signaling
      partners. Because these unique signaling responses result from specific receptor
      active conformations, GPCR signaling may be directed toward these selective
      responses through either strength-of-signal effects resulting from partial
      agonism or through biased agonism and functional selectivity, resulting from the
      selective stabilization of one active conformation over the others. This review
      uses the CB(1) cannabinoid receptor as a specific example to highlight the
      contribution of two important aspects of GPCR function-orthosteric ligand binding
      and receptor heterodimerization-toward directed GPCR signaling.

PMID- 19837904
TI  - Selective and brain penetrant neuropeptide y y2 receptor antagonists discovered
      by whole-cell high-throughput screening.
AB  - The role of neuropeptide Y Y2 receptor (Y2R) in human diseases such as obesity,
      mood disorders, and alcoholism could be better resolved by the use of small
      molecule chemical probes that are substantially different from the currently
      available Y2R antagonist, N-[(1S)-4-[(aminoiminomethyl)amino]-1-[[[2-(3,5-dioxo
      1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]amino]carbonyl]butyl]-1-[2-[4-(6,11
      dihydro-6-oxo-5H-dibenz[b,e]azepin-11-yl)-1-piperazinyl]-2-oxoethyl]
      cyclopentaneacetamide) (BIIE0246). Presented here are five potent, selective, and
      publicly available Y2R antagonists identified by a high-throughput screening
      approach. These compounds belong to four chemical scaffolds that are structurally
      distinct from the peptidomimetic BIIE0246. In functional assays, IC(50) values
      between 199 and 4400 nM against the Y2R were measured, with no appreciable
      activity against the related NPY-Y1 receptor (Y1R). Compounds also displaced
      radiolabeled peptide YY from the Y2R with high affinity (K(i) values between 1.55
      and 60 nM) while not displacing the same ligand from the Y1R. In contrast to
      BIIE0246, Schild analysis with NPY suggests that two of the five compounds behave
      as competitive antagonists. Profiling against a panel of 40 receptors, ion
      channels, and transporters found in the central nervous system showed that the
      five Y2R antagonists demonstrate greater selectivity than BIIE0246. Furthermore,
      the ability of these antagonists to penetrate the blood-brain barrier makes them
      better suited for pharmacological studies of Y2R function in both the brain and
      periphery.

PMID- 19837906
TI  - Clinical pharmacokinetics and exposure-toxicity relationship of a folate-Vinca
      alkaloid conjugate EC145 in cancer patients.
AB  - The clinical pharmacokinetics and exposure-toxicity relationship were determined
      for EC145, a conjugate of folic acid and the Vinca alkaloid desacetylvinblastine
      hydrazide (DAVLBH), in cancer patients. EC145 plasma concentration and toxicity
      data were obtained from a first-in-man phase I study and analyzed by nonlinear
      mixed effect modeling with NONMEM. EC145 concentration-time profile after
      intravenous administration was well described by a 2-compartment model with a
      first-order elimination process from the central compartment. BSA was identified
      as a significant covariate on EC145 clearance, accounting for 14.6% of
      interindividual variation on EC145 clearance. Population estimates for the
      clearance, steady-state volume of distribution, distribution, and elimination
      half-lives were 56.1 L/h, 26.1 L, 6 minutes, and 26 minutes, respectively.
      Constipation and peripheral neuropathy were the most common and clinically
      relevant toxicities. The clearance and area under the concentration-time curve
      (AUC) were significant predictors for the incidence of EC145-induced constipation
      but not peripheral neuropathy. In conclusion, EC145 is rapidly distributed and
      eliminated in cancer patients. BSA is a statistically significant covariate on
      EC145 clearance, but its clinical relevance remains to be defined. EC145-induced
      constipation occurs at a higher frequency in the patients with lower EC145
      clearance, where the drug exposure tends to be higher.

PMID- 19837907
TI  - Interspecies scaling of therapeutic monoclonal antibodies: initial look.
AB  - The authors evaluated interspecies scaling for the prediction of human clearance
      of 18 therapeutic monoclonal antibodies (mAbs). Human and monkey/chimpanzee data
      of 14 mAbs were classified based on the targeted antigens (soluble or membrane
      bound). Simple allometry and/or a time-invariant method (elementary Dedrick plot)
      were performed. Results indicate that human clearance might be accurately
      predicted from monkey data for mAbs targeting soluble receptors or membrane-bound
      receptors with limited tissue distribution using simplified allometry. The
      optimal exponents were estimated to be 0.85 or 0.90. If nonlinearity is
      anticipated at the human efficacious dose, pharmacokinetic parameters obtained at
      high doses in animals might not be sufficient for full pharmacokinetic
      characterization and prediction. Using prespecified criteria, including predicted
      human clearance (< or = or > 10 mL/d/kg), simplified allometric scaling might be
      helpful in predicting the effect of receptor-mediated clearance for mAbs
      targeting membrane-bound antigens. Furthermore, simplified allometry and an
      elementary Dedrick plot provide similar results in predicted clearance. Given the
      significant advantages offered by simplified allometry, it should be used when
      data are available from only 1 species. When reasonable data from > or =3 species
      are available, traditional allometry should be explored. Overall, clearance
      prediction is useful for human dose prediction in drug discovery and development.

PMID- 19837908
TI  - Influence of development, HIV infection, and antiretroviral therapies on the gene
      expression profiles of ABC transporters in human lymphocytes.
AB  - The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive,
      and antiretroviral drugs depends on their intracellular concentrations, which
      could be modulated by membrane efflux pumps belonging to the ABC transporter
      superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1,
      MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to
      adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV
      infected, respectively). Gene expression levels were quantified by quantitative
      RT-PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5
      gene. BCRP and MRP4 genes were significantly higher expressed at birth than after
      1 month of life. Neither HIV infection nor antiretroviral therapies modulated the
      gene expression profiles of ABC transporters. In conclusion, drugs that are
      substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in
      newborns.

PMID- 19837909
TI  - Cinacalcet treatment of primary hyperparathyroidism: biochemical and bone
      densitometric outcomes in a five-year study.
AB  - CONTEXT: Primary hyperparathyroidism (PHPT) is characterized by chronically
      elevated serum calcium and inappropriately normal or increased PTH. OBJECTIVE:
      Our objective was to evaluate long-term tolerability, safety, and efficacy of
      cinacalcet in PHPT patients. DESIGN AND SETTING: A 4.5-yr open-label extension
      study was conducted at 14 study centers in the United States. PATIENTS OR OTHER
      PARTICIPANTS: Forty-five subjects with PHPT from a double-blind, placebo
      controlled, 1-yr trial were continued into this study. INTERVENTIONS: After the
      parent study, all subjects were treated with 30 mg cinacalcet twice daily,
      increasing to 50 mg twice daily during the 12-wk titration if serum calcium
      levels were 10.3 mg/dl or higher and then maintained on cinacalcet for up to 4.5
      yr. MAIN OUTCOME MEASURES: Assessments included serum calcium, PTH, phosphate and
      alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety
      chemistries and hematology, and adverse events were monitored throughout.
      RESULTS: Compared with baseline, cinacalcet treatment improved biochemical
      measures of PHPT including reducing serum calcium and PTH and increasing serum
      phosphate with slight increases in alkaline phosphatase. No changes in z-scores
      of aBMD at spine, hip, or wrist were seen with annual percent changes, consistent
      with reports for untreated postmenopausal women or PHPT patients. Safety
      biochemistries remained normal, and adverse events (most commonly arthralgia,
      myalgia, diarrhea, respiratory infection, and nausea) were mild to moderate in
      severity. CONCLUSIONS: Treatment of PHPT patients with cinacalcet for up to 5.5
      yr maintained normocalcemia, reduced plasma PTH, increased serum phosphate and
      alkaline phosphatase with no significant effects on aBMD, and was well tolerated.

PMID- 19837910
TI  - Clinical, genetic, and enzymatic characterization of P450 oxidoreductase
      deficiency in four patients.
AB  - CONTEXT: P450 oxidoreductase (POR) deficiency causes disordered steroidogenesis;
      severe mutations cause genital ambiguity in both sexes plus the Antley-Bixler
      skeletal malformation syndrome, whereas mild mutations can cause adult
      infertility. OBJECTIVE: We describe four patients with POR deficiency and
      identify and characterize the activities of their mutations. A 46,XY male with
      micropenis and two 46,XX female infants with genital ambiguity presented with
      skeletal malformations, and a 46,XX adolescent presented with primary amenorrhea,
      elevated 17alpha-hydroxyprogesterone, and low sex steroids. METHODS: The coding
      regions of the POR gene were sequenced, and the identified mutations were
      recreated in human POR cDNA expression vectors lacking 27 N-terminal residues.
      POR and human P450c17 were expressed in bacteria. POR activity was measured by
      four assays: reduction of cytochrome c, oxidation of reduced nicotinamide adenine
      dinucleotide phosphate, and support of the 17alpha-hydroxylase and 17,20 lyase
      activities of P450c17. RESULTS: All four patients were compound heterozygotes for
      POR mutations, including five novel mutations: L577R, N185K, delE217, and
      frameshift mutations 1363delC and 697-698insGAAC. N185K and delE217 lacked
      measurable activity in the assays based on P450c17 but retained partial activity
      in the assays based on cytochrome c. As assessed by V(max)/Km, L577R supported
      46% of 17alpha-hydroxylase activity but only 27% of 17,20 lyase activity.
      Computational modeling of these novel mutants revealed the structural basis for
      their reduced or absent activities. CONCLUSION: These patients illustrate the
      broad clinical spectrum of POR deficiency, including amenorrhea and infertility
      as the sole manifestation. POR assays based on P450c17 correlate well with
      hormonal and clinical phenotypes.

PMID- 19837912
TI  - 11Beta-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus
      pituitary-adrenal axis, metabolic syndrome, and inflammation.
AB  - CONTEXT: 11Beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes are now
      appreciated to be important regulators of hormone action at a tissue level.
      11Beta-HSD1 is widely expressed and increases glucocorticoid action through its
      unique ability to convert inactive glucocorticoids (cortisone in man, 11
      dehydrocorticosterone in rodents) to their active forms (cortisol and
      corticosterone, respectively). The enzyme has roles in the normal hypothalamus
      pituitary-adrenal (HPA) axis, has been implicated in metabolic syndrome, and may
      modulate various aspects of the immune response. EVIDENCE ACQUISITION: A review
      of published, peer-reviewed medical literature (1990 to June 2009) on the
      physiology and pathophysiology of 11beta-HSD1 was performed with an emphasis on
      HPA axis consequences, the metabolic syndrome, and the inflammatory response.
      EVIDENCE SYNTHESIS: Studies of patients with genetic defects in 11beta-HSD1
      action show abnormal HPA axis responses with hyperandrogenism being a major
      consequence. The mechanisms underlying these abnormalities have been explored in
      mouse models with targeted deletion of components of the 11beta-HSD1 system. A
      range of experimental studies emphasize the role of 11beta-HSD1 in the metabolic
      syndrome and the potential for treatment with chemical inhibitors. An emerging
      area is the role of 11beta-HSD1 in the inflammatory response. CONCLUSIONS: 11Beta
      HSD1 activity is an important component of the HPA axis and contributes to the
      metabolic syndrome and the normal immune response. Ongoing clinical observations
      and the development of selective inhibitors will further clarify the role of
      11beta-HSD1 in these areas.

PMID- 19837911
TI  - N-terminal propeptide of type III procollagen as a biomarker of anabolic response
      to recombinant human GH and testosterone.
AB  - CONTEXT: Biomarkers that predict musculoskeletal response to anabolic therapies
      should expedite drug development. During collagen synthesis in soft lean tissue,
      N-terminal propeptide of type III procollagen (P3NP) is released into
      circulation. We investigated P3NP as a biomarker of lean body mass (LBM) and
      muscle strength gains in response to testosterone and GH. DESIGN: Community
      dwelling older men received GnRH agonist plus 5 or 10 g testosterone gel plus 0,
      3, or 5 microg recombinant human GH daily. P3NP levels were measured at baseline
      and wk 4, 8, 12, and 16. LBM and appendicular skeletal muscle mass (ASM) were
      measured by dual-energy x-ray absorptiometry. RESULTS: One hundred twelve men
      completed treatment; 106 underwent serum P3NP measurements. P3NP levels were
      higher at wk 4 than baseline (6.61 +/- 2.14 vs. 4.51 +/- 1.05, P < 0.0001) and
      reached plateau by wk 4 in men receiving testosterone alone. However, wk 8 P3NP
      levels were higher than wk 4 levels in men receiving testosterone plus
      recombinant human GH. Increases in P3NP from baseline to wk 4 and 16 were
      significantly associated with gains in LBM (r = 0.26, P = 0.007; r = 0.53, P <
      0.001) and ASM (r = 0.17, P = 0.07; r = 0.40, P < 0.0001). Importantly, for
      participants receiving only testosterone, P3NP increases at wk 4 and 16 were
      related to muscle strength gains (r = 0.20, P = 0.056 and r = 0.36, P = 0.04). In
      stepwise regression, change in P3NP explained 28 and 30% of the change in ASM and
      LBM, respectively, whereas change in testosterone but not IGF-I and age provided
      only small improvements in the models. CONCLUSION: Early changes in serum P3NP
      levels are associated with subsequent changes in LBM and ASM during testosterone
      and GH administration. Serum P3NP may be a useful early predictive biomarker of
      anabolic response to GH and testosterone.

PMID- 19837913
TI  - High prevalence of metabolic syndrome in first-degree male relatives of women
      with polycystic ovary syndrome is related to high rates of obesity.
AB  - CONTEXT: Women with polycystic ovary syndrome (PCOS) have twice the risk for
      metabolic syndrome (MetS) compared to women from the general population. Mothers
      and sisters of affected women also have an increased prevalence of MetS.
      OBJECTIVE: The aim of the study was to determine the prevalence of MetS in
      fathers and brothers of women with PCOS compared to men from the general
      population. DESIGN AND SETTING: We conducted a cross-sectional observational
      study at academic medical centers. PARTICIPANTS: A total of 211 fathers and 58
      brothers of women with PCOS were studied and compared to 1153 and 582 Third
      National Health and Nutrition Survey (NHANES III) men of similar age and
      race/ethnicity, respectively. MAIN OUTCOME MEASURE: We measured MetS prevalence.
      RESULTS: The prevalence of MetS was increased in fathers (42 vs. 32%; P = 0.006)
      and brothers (22 vs. 9%; P = 0.001) compared to NHANES III men. Fathers and
      brothers had higher body mass index (BMI) than NHANES III men (P < 0.0001). MetS
      rates were similar in fathers and brothers compared to NHANES III groups after
      adjusting for BMI. Total testosterone was inversely related to MetS in both
      fathers and brothers, but this relationship was also accounted for by the higher
      BMI in male relatives. CONCLUSION: Male relatives of women with PCOS had
      increased prevalence rates of MetS and obesity compared to the general U.S. male
      population from NHANES III. In contrast to women with PCOS and their female
      relatives, the higher prevalence of MetS in male relatives was accounted for by
      elevated BMI. These findings suggest that the high rates of MetS in male
      relatives of women with PCOS are related to higher rates of obesity than the
      general population.

PMID- 19837914
TI  - Reduced growth hormone secretion is associated with increased carotid intima
      media thickness in obesity.
AB  - CONTEXT: Obesity is associated with reduced GH. OBJECTIVE: The aim of the study
      was to determine whether reduced GH is associated with increased carotid intima
      media thickness (cIMT) in obesity. DESIGN: A total of 102 normal-weight and obese
      men and women without known hypopituitarism were studied. Subjects underwent GH
      stimulation testing with GHRH-arginine. Lipid profile, inflammatory markers, oral
      glucose tolerance test, abdominal computed tomography, dual-energy x-ray
      absorptiometry, and cIMT were measured. Relative GH deficiency was defined as
      peak GH of 4.2 microg/liter or less. Subjects were separated based on BMI and GH
      testing into three groups: normal weight, obese GH sufficient (GHS), and obese
      relative GH deficient (GHD). Age, gender, and race were similar between the
      groups. BMI, percentage body fat, and visceral adiposity did not differ between
      obese GHS and relative GHD. RESULTS: Peak GH was associated with cIMT, IGF-I,
      high-density lipoprotein, low-density lipoprotein, triglycerides, adiponectin, C
      reactive protein, and TNF-alpha (all P < 0.05). Obese GHS subjects had similar
      cIMT compared to normal-weight subjects (P = not significant), whereas obese GHD
      subjects had higher cIMT compared to normal-weight subjects (P < 0.05) (normal
      weight, 0.645 +/- 0.023, vs. obese GHS, 0.719 +/- 0.021, vs. obese GHD, 0.795 +/-
      0.063 mm; P = 0.01 by ANOVA). Similar results were seen in sensitivity analyses
      with less stringent cutoffs (< 5, < or = 8, < 9 microg/liter) to define GHD. In
      multivariate modeling, peak GH remained significantly associated with cIMT after
      controlling for age, gender, race, tobacco, blood pressure, cholesterol, and
      fasting glucose (R(2) for model, 0.35; P < 0.0001). CONCLUSIONS: These results
      suggest that reduced GH secretion is associated with a more abnormal metabolic
      phenotype in obesity, characterized by increased cIMT, dyslipidemia, insulin
      resistance, and inflammation.

PMID- 19837915
TI  - Heritabilities of the metabolic syndrome phenotypes and related factors in Korean
      twins.
AB  - CONTEXT: The genetic studies of metabolic syndrome (MetS), individual components,
      or latent factors of MetS phenotypes, in Asian populations are limited.
      OBJECTIVE: This study aimed to estimate heritability of MetS and its components,
      and to identify latent factors clustering individual components among Korean
      twins and their families. DESIGN: Data were derived from the Healthy Twin Study,
      an ongoing cohort study, from April 2005 to December 2008. PARTICIPANTS: A total
      of 1942 Korean adult same-sex twins and their families (728 men, 1214 women; 795
      monozygotic and 229 dizygotic twin individuals with 918 nontwin family members).
      MAIN OUTCOME MEASURES: MetS phenotypes measured were waist circumference (WC),
      mean blood pressure (MBP), glucose, high-density lipoprotein cholesterol (HDL),
      and triglycerides (TG) as continuous and discrete traits. MetS was defined using
      Adult Treatment Panel III and International Diabetes Federation criteria.
      Heritability, bivariate analyses, interclass correlation, concordances, and
      factor analyses were conducted. RESULTS: Significant differences in interclass
      correlation for WC, MBP, HDL, and glucose and in concordance rate for high WC and
      low HDL among monozygotic and dizygotic twins were found. MetS had heritabilities
      of 51-60% (P < 0.001), and phenotypes showed adjusted heritabilities ranging from
      46% (for TG) to 77% (for low HDL). Factor analysis indicated two latent factors
      (factor 1, TG/WC/HDL; factor 2, WC/MBP/glucose) with significant heritabilities
      of 60-63%. Bivariate analyses exhibited different genetic and environmental
      interrelationships between phenotype pairs, although WC and TG showed significant
      genetic correlations with all other phenotypes. CONCLUSIONS: Significant genetic
      contributions for MetS, its related phenotypes, and latent factors comprising
      MetS are confirmed.

PMID- 19837916
TI  - RAS mutations are the predominant molecular alteration in poorly differentiated
      thyroid carcinomas and bear prognostic impact.
AB  - CONTEXT: Poorly differentiated carcinomas represent an aggressive group of
      thyroid tumors with controversial classification placement and poorly understood
      pathogenesis. Molecular data in this group of tumors are extremely heterogeneous,
      possibly reflecting different inclusion criteria. Recently homogeneous diagnostic
      criteria have been proposed by our group (Turin proposal) that need to be
      complemented by detailed molecular characterization. OBJECTIVE: The objective of
      the study was to define a comprehensive molecular typing of poorly differentiated
      thyroid carcinomas classified following homogeneous diagnostic criteria. DESIGN:
      Sixty-five cases of poorly differentiated carcinoma selected following the Turin
      proposal have been screened for N-, K-, H-RAS, BRAF, RET/PTC1 and 3, and
      PAX8/PPARgamma mutations-rearrangements using alternative techniques and in two
      different laboratories. Molecular data were compared with clinical pathological
      parameters and survival by univariate and multivariate analysis. RESULTS: RAS
      mutations in codon 61 were by far the most common genetic alteration in poorly
      differentiated carcinomas (23% of cases), with all mutation in NRAS except one in
      the HRAS gene. A single BRAF mutation was found in a poorly differentiated
      carcinoma with a residual component of a tall cell variant of papillary
      carcinoma. No KRAS, RET/PTC, or PAX8/PPARgamma genetic alteration was detected.
      In this series, the presence of RAS mutations was a unique negative prognostic
      parameter at multivariate analysis. CONCLUSIONS: The present study demonstrates
      that strictly classified poorly differentiated carcinomas are genetically
      homogeneous, RAS mutations being the almost exclusive genetic event. Moreover,
      the detection of RAS mutations might be clinically relevant for the prognostic
      stratification of these tumors.

PMID- 19837917
TI  - Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal
      diabetes in consanguineous families.
AB  - CONTEXT AND OBJECTIVE: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome
      (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal
      abnormalities, and liver dysfunction. Although early diagnosis is important for
      clinical management, genetic testing is generally performed after the full
      clinical picture develops. We aimed to identify patients with WRS before any
      other abnormalities apart from diabetes are present and study the overall
      frequency of WRS among patients with permanent neonatal diabetes. RESEARCH DESIGN
      AND METHODS: The coding regions of EIF2AK3 were sequenced in 34 probands with
      infancy-onset diabetes with a clinical phenotype suggestive of WRS (n = 28) or
      homozygosity at the WRS locus (n = 6). RESULTS: Twenty-five probands (73.5%) were
      homozygous or compound heterozygous for mutations in EIF2AK3. Twenty of the 26
      mutations identified were novel. Whereas a diagnosis of WRS was suspected before
      genetic testing in 22 probands, three patients with apparently isolated diabetes
      were diagnosed after identifying a large homozygous region encompassing EIF2AK3.
      In contrast to nonconsanguineous pedigrees, mutations in EIF2AK3 are the most
      common known genetic cause of diabetes among patients born to consanguineous
      parents (24 vs. < 2%). Age at diabetes onset and birth weight might be used to
      prioritize genetic testing in the latter group. CONCLUSIONS: WRS is the most
      common cause of permanent neonatal diabetes mellitus in consanguineous pedigrees.
      In addition to testing patients with a definite clinical diagnosis, EIF2AK3
      should be tested in patients with isolated neonatal diabetes diagnosed after 3 wk
      of age from known consanguineous families, isolated populations, or countries in
      which inbreeding is frequent.

PMID- 19837918
TI  - Latent autoimmune diabetes in adults.
AB  - CONTEXT: Autoantibodies that are reactive to islet antigens are present at the
      time of diagnosis in most patients with type 1 diabetes. Additionally,
      approximately 10% of phenotypic type 2 diabetic patients are positive for at
      least one of the islet autoantibodies, and this group is often referred to as
      "latent autoimmune diabetes in adults (LADA)." These patients share many genetic
      and immunological similarities with type 1 diabetes, suggesting that LADA, like
      type 1 diabetes, is an autoimmune disease. However, there are differences in
      autoantibody clustering, T cell reactivity, and genetic susceptibility and
      protection between type 1 diabetes and LADA, implying important differences in
      the underlying disease processes. EVIDENCE ACQUISITION AND SYNTHESIS: In this
      clinical review, we will summarize the current understanding of LADA based on the
      MEDLINE search of all peer-reviewed publications (original articles and reviews)
      on this topic between 1974 and 2009. CONCLUSIONS: In LADA, diabetes occurs
      earlier in the beta-cell-destructive process because of the greater insulin
      resistance. Complexities arise also because of variable definitions of LADA and
      type 1 diabetes in adults. As immunomodulatory therapies that slow or halt the
      type 1 diabetes disease process are discovered, testing these therapies in LADA
      will be essential.

PMID- 19837920
TI  - Role of fat hydrolysis in regulating glucagon-like Peptide-1 secretion.
AB  - CONTEXT: Glucagon-like peptide-1 (GLP-1) is produced by specialized cells in the
      gut and secreted in response to carbohydrates and lipids. The mechanisms
      regulating fat-stimulated GLP-1 release have, however, not been clarified in
      detail. AIM: We aimed to investigate the effect of intraduodenal (ID) fat
      hydrolysis on GLP-1 release and test whether the signal is mediated through
      cholecystokinin (CCK)-1 receptors. DESIGN AND SETTING: Thirty-four healthy, male
      ambulatory volunteers were studied in three consecutive, randomized, double
      blind, crossover studies. INTERVENTION: There were three interventions: 1) 12
      subjects received an ID fat infusion with or without orlistat, an irreversible
      inhibitor of gastrointestinal lipases, in comparison with vehicle; 2) 12 subjects
      received ID sodium oleate (C18:1), ID sodium caprylate (C8:0), or ID vehicle; and
      3) 10 subjects received ID sodium oleate with and without the CCK-1 receptor
      antagonist dexloxiglumide or ID vehicle plus iv saline (placebo). The effect of
      these treatments on GLP-1 concentrations and CCK release was quantified. RESULTS:
      The following results were reached: 1) ID fat induced significant increase in GLP
      1 concentrations (P < 0.004), and inhibition of fat hydrolysis by orlistat
      abolished this effect; 2) sodium oleate significantly stimulated GLP-1 release (P
      < 0.008), whereas sodium caprylate was ineffective compared with controls; and 3)
      dexloxiglumide administration abolished the effect of sodium oleate on GLP-1. ID
      fat or sodium oleate significantly stimulated plasma CCK (P < 0.006 and P <
      0.004) compared with saline, whereas sodium caprylate did not. CONCLUSION:
      Generation of long-chain fatty acids through hydrolysis of fat is a critical step
      for fat-induced stimulation of GLP-1 in humans; the signal is mediated via CCK
      release and CCK-1 receptors.

PMID- 19837919
TI  - Activating autoantibodies against the calcium-sensing receptor detected in two
      patients with autoimmune polyendocrine syndrome type 1.
AB  - CONTEXT: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal
      recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene.
      Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to
      result from an autoimmune reaction against the calcium-sensing receptor (CaSR) in
      parathyroid cells. Anti-CaSR binding antibodies have previously been detected in
      patients with APS1. OBJECTIVE: The aim of this study was to determine whether
      anti-CaSR antibodies present in APS1 patients could modulate the response of the
      CaSR to stimulation by Ca(2+). RESULTS: The results indicated that two of the 14
      APS1 patients included in the study had anti-CaSR antibodies that stimulated the
      receptor. These antibodies were detected by their ability to increase both Ca(2+)
      dependent extracellular signal-regulated kinase phosphorylation and inositol
      phosphate accumulation in human embryonic kidney 293 cells expressing the CaSR.
      CONCLUSION: An important implication of the present results is that although the
      majority of APS1 patients do not have CaSR-stimulating antibodies, there may be a
      small but substantial minority of patients in whom the hypoparathyroid state is
      the result of functional suppression of the parathyroid glands rather than their
      irreversible destruction.

PMID- 19837921
TI  - Hypercortisolemia is associated with severity of bone loss and depression in
      hypothalamic amenorrhea and anorexia nervosa.
AB  - CONTEXT: Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are
      associated with low bone density, anxiety, and depression. Women with AN and HA
      have elevated cortisol levels. Significant hypercortisolemia, as in Cushing's
      disease, causes bone loss. It is unknown whether anxiety and depression and/or
      cortisol dysregulation contribute to low bone density in AN or HA. OBJECTIVE: Our
      objective was to investigate whether hypercortisolemia is associated with bone
      loss and mood disturbance in women with HA and AN. DESIGN AND SETTING: We
      conducted a cross-sectional study in a clinical research center. PARTICIPANTS: We
      studied 52 women [21 healthy controls (HC), 13 normal-weight women with
      functional HA, and 18 amenorrheic women with AN]. OUTCOME MEASURES: Serum samples
      were measured every 20 min for 12 h overnight and pooled for average cortisol
      levels. Bone mineral density (BMD) was assessed by dual-energy x-ray
      absorptiometry (DXA) at anteroposterior and lateral spine and hip. Hamilton
      Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) were administered.
      RESULTS: BMD was lower in AN and HA than HC at all sites and lower in AN than HA
      at the spine. On the HAM-D and HAM-A, AN scored higher than HA, and HA scored
      higher than HC. Cortisol levels were highest in AN, intermediate in HA, and
      lowest in HC. HAM-A and HAM-D scores were associated with decreased BMD. Cortisol
      levels were positively associated with HAM-A and HAM-D scores and negatively
      associated with BMD. CONCLUSIONS: Hypercortisolemia is a potential mediator of
      bone loss and mood disturbance in these disorders.

PMID- 19837922
TI  - Influence of preterm birth and birth size on gonadal function in young men.
AB  - BACKGROUND/OBJECTIVES: Preterm birth has been associated with reduced
      reproduction rates and being born small for gestational age (SGA) with reduced
      gonadal function. We hypothesized that alterations concerning gonadal function in
      young men are not due to preterm birth or being born SGA, but are due to other
      (environmental) factors. METHODS: In 207 young men of the PROGRAM/PREMS cohort
      study, aged 18-24 yr, the influence of preterm birth, birth length, and birth
      weight on serum levels of anti-Mullerian hormone, inhibin B, testosterone, SHBG,
      non-SHBG-bound testosterone, LH, and FSH was analyzed with multiple regression
      modeling. In addition, markers of male gonadal function were analyzed in four
      subgroups: men born SGA with either short stature or catch-up growth, or men born
      appropriate for gestational age with idiopathic short stature or with normal
      stature (control). RESULTS: Preterm birth and SGA did not affect gonadal
      function. After adjustment for age, birth size, adult height, fat mass, and
      socioeconomic status (SES), preterm birth even showed a positive relation with
      inhibin B. Higher SES was associated with higher inhibin B levels. Higher fat
      mass was associated with decreased testosterone and SHBG levels and maternal
      smoking with increased LH and non-SHBG-bound testosterone levels. After
      adjustment for confounders, there were no significant differences in gonadal
      function between the subgroups. CONCLUSION: Preterm birth and SGA did not affect
      gonadal function in young men. Factors that affected gonadal function were: lower
      SES, a higher fat mass, and maternal smoking during pregnancy.

PMID- 19837923
TI  - Bone microarchitecture and stiffness in premenopausal women with idiopathic
      osteoporosis.
AB  - CONTEXT: Idiopathic osteoporosis (IOP) is an uncommon disorder in which low areal
      bone mineral density (aBMD) and/or fractures occur in otherwise healthy
      premenopausal women. OBJECTIVES: Our objectives were to characterize bone mass,
      microarchitecture, and trabecular bone stiffness in premenopausal IOP and to
      determine whether women with low aBMD who have never fractured have abnormal
      microarchitecture and stiffness. DESIGN, SETTING, AND PATIENTS: We conducted a
      prospective cohort study of 27 normal controls and 31 women with IOP defined by
      low trauma fracture (n = 21) or low BMD (Z score <or=-2.0; n = 10). MAIN OUTCOME
      MEASURES: We assessed aBMD by dual-energy x-ray absorptiometry; volumetric BMD
      and cortical and trabecular microarchitecture of the radius and tibia by high
      resolution (82 microm) peripheral quantitative computed tomography; and
      trabecular bone stiffness (elastic moduli), estimated by micro-finite element
      analysis. RESULTS: Fracture subjects did not differ from controls by age or body
      mass index, which was lower in low-BMD subjects than controls. Fracture subjects
      also had lower aBMD than controls at all sites (P < 0.05-0.0001). Bone size was
      similar in controls and fracture subjects but 10.6% smaller in low-BMD subjects
      (P < 0.05). Every trabecular parameter in both fracture and low-BMD groups was
      markedly worse than controls (P < 0.01-0.0001). Cortical thickness was
      significantly lower in both fracture and low-BMD groups at the tibia but not
      radius. Bone stiffness estimated by micro-finite element analysis was comparably
      reduced in low-BMD and fracture groups. CONCLUSION: Premenopausal women with IOP
      had marked trabecular microarchitectural deterioration at the radius and tibia.
      Cortical parameters were affected only at the tibia. Although they had not
      fractured, microarchitectural deterioration was similar in IOP women with low BMD
      and those with fractures.

PMID- 19837925
TI  - Mild sleep restriction acutely reduces plasma glucagon levels in healthy men.
AB  - BACKGROUND: Sleep loss has repeatedly been suggested to affect glucose metabolism
      adversely, raising the question as to the impact of subtle forms of sleep loss.
      OBJECTIVE: The aim of the study was to assess the effects of a single night of
      sleep restriction to 4.5 h on endocrine parameters of glucose metabolism. DESIGN:
      We conducted crossover, balanced experiments including two conditions, i.e. one
      night of 4.5 h and one night of 7 h of sleep. SUBJECTS AND MEASUREMENTS: In 10
      healthy men, circulating concentrations of insulin, C-peptide, epinephrine,
      norepinephrine, GH, ACTH, cortisol, and glucagon were measured after sleep and
      sleep restriction, respectively, during basal rest and a subsequent stepwise
      hypoglycemic clamp. RESULTS: Mild sleep restriction induced a robust reduction in
      basal plasma glucagon levels that persisted throughout the hypoglycemic clamp (P
      < 0.03). Basal glucose, insulin, and C-peptide levels were unaffected by sleep
      restriction. Also, basal and hypoglycemia-stimulated concentrations of
      epinephrine, norepinephrine, and GH were unchanged after sleep restriction.
      Concentrations of ACTH (P < 0.05) and cortisol (P < 0.001) were reduced after
      sleep loss during baseline and at the start of hypoglycemia, but reached roughly
      comparable levels in both conditions at the end of the clamp (ACTH, P > 0.06;
      cortisol, P > 0.93). CONCLUSION: Our data show that mild restriction of nocturnal
      sleep to 4.5 h has a reducing effect on circulating glucagon levels. This finding
      provides further evidence for the notion that glucose homeostasis is sensitive to
      subtle changes in sleep duration.

PMID- 19837924
TI  - Maternal smoking and developmental changes in luteinizing hormone (LH) and the LH
      receptor in the fetal testis.
AB  - CONTEXT: The LH receptor (LHCGR) drives fetal testosterone secretion, which is
      vital for human masculinization. Maternal smoking is associated with defective
      masculinization, but the relationship between smoking, tropic hormones,
      testosterone, and functional LHCGR expression is poorly understood. OBJECTIVE:
      This study aimed to investigate developmental changes in fetal gonadotropins,
      human chorionic gonadotropin (hCG), and expression of fetal testicular LHCGR
      isoforms and the effects of maternal cigarette smoking. DESIGN: We conducted an
      observational study of the male fetus, comparing pregnancies in which the mothers
      did or did not smoke. SETTING: The study was conducted at the Universities of
      Aberdeen and Glasgow. PATIENTS/PARTICIPANTS: Testes and blood were collected from
      54 morphologically normal human male fetuses of women undergoing elective
      termination of normal second-trimester pregnancies. MAIN OUTCOME MEASURES: We
      measured circulating testosterone, hCG, LH, prolactin, FSH, and testicular LHCGR
      isoform expression. RESULTS: Fetal testosterone and hCG, but not LH,
      significantly declined between 11 and 19 wk gestation with no significant change
      in testicular responsiveness. The proportion of nonfunctional LHCGR transcript in
      fetal testes was 2.3-fold lower than in adults. Fetal hCG was reduced 38% (P =
      0.021) and the ratio of inactive vs. active LHCGR isoforms lowered by smoking.
      CONCLUSIONS: Falling second-trimester fetal testosterone is probably due to
      declining maternal hCG because Leydig cell LH/hCG responsiveness remains
      constant. Although maternal cigarette smoking reduces fetal hCG, the ratio of
      inactive LHCGR isoforms is reduced and gonadotropin drive maintains testosterone
      production near control levels. The lower relative abundance of inactive isoforms
      compared with the adult testis reflects the importance of LHCGR.

PMID- 19837926
TI  - Defective O-glycosylation due to a novel homozygous S129P mutation is associated
      with lack of fibroblast growth factor 23 secretion and tumoral calcinosis.
AB  - BACKGROUND: Homozygous mutations in fibroblast growth factor (FGF23) have
      recently been described as the genetic cause of one form of hyperphosphatemic
      tumoral calcinosis (HFTC). However, it remained unclear to date how these
      mutations lead to loss of biologically active FGF23 in the circulation. METHODS:
      We here report a novel homozygous mutation, c.385T>C in FGF23 exon 2, which
      changes codon 129 from serine to proline (S129P) in a previously described
      individual affected by HFTC. The S129P mutation as well as two known FGF23
      mutations, S71G and S129F, were introduced into an expression vector encoding
      wild-type (wt) human (h) FGF23 to yield [P129]hFGF23, [F129]hFGF23, and
      [G71]hFGF23; whole lysates, glycoprotein fractions, and conditioned media from
      HEK293 and COS-7 cells expressing these constructs were subjected to Western blot
      analysis using affinity-purified goat anti-hFGF23(51-69) and anti-hFGF23(206-222)
      antibodies. RESULTS: We detected 25- and 32-kDa protein species in total lysates
      of HEK293 cells expressing wt-hFGF23. The 32-kDa band, representing O
      glycosylated hFGF23, was not detectable in the glycoprotein fraction of lysates
      from HEK293 cells expressing [P129]hFGF23, and in comparison with wt-FGF23 only
      small amounts of [P129]hFGF23 were secreted into the medium. Similar results were
      obtained for cells expressing [G71]hFGF23 and [F129]hFGF23. CONCLUSION: Our data
      for the first time directly show that FGF23 mutations associated with HFTC impair
      O-glycosylation in vitro resulting in poor secretion of the mutant hormone
      thereby explaining the characteristic hyperphosphatemic phenotype of homozygous
      carriers in vivo.

PMID- 19837927
TI  - Adipose tissue collagen VI in obesity.
AB  - OBJECTIVES: Basic science studies show that the extracellular matrix of adipose
      tissue, mainly represented by collagen VI, is dysfunctional in obesity and
      contributes to the development of the metabolic syndrome. We hypothesized in
      humans that increased collagen VI alpha3-subunit (COL6A3) mRNA is associated with
      adipose tissue macrophage chemotaxis and inflammation and that weight gain is
      accompanied by changes in the expression of COL6A3. RESEARCH DESIGN AND METHODS:
      Adipose tissue biopsies were obtained from a cross-sectional study (n = 109), an
      overfeeding study (n = 9), and a pioglitazone treatment study (n = 14). Adipose
      tissue gene expression was measured by quantitative RT-PCR, immunohistochemistry,
      and adipocyte sizing by fixation with osmium and Coulter counting. Body
      composition was measured by dual-energy x-ray absorptiometry and visceral adipose
      tissue by computed tomography. Patients with high or low COL6A3 mRNA were
      compared by one-way ANOVA. RESULTS: In humans, immunohistochemistry revealed that
      COL6 is present in adipose tissue extracellular matrix. COL6A3 mRNA is correlated
      with body mass index (r = 0.60, P < 0.0001) and fat mass (r = 0.41, P < 0.0001).
      COL6A3 expression was similar in obese vs. type 2 diabetes patients. Obese
      subjects with high COL6A3 mRNA had greater visceral adipose tissue mass (P <
      0.05), lower size of small and medium adipocytes (P < 0.05), more CD68+ and
      CD163/MAC2+ macrophages, and increased macrophage inflammatory protein-1alpha and
      macrophage chemoattractant protein-1alpha mRNA (P < 0.05). Eight weeks of
      overfeeding increased body weight and COL6A3 mRNA (P < 0.05). Pioglitazone
      decreased COL6A3 mRNA, and the change was inversely proportional to baseline
      COL6A3 mRNA (r = -0.95, P < 0.0001). CONCLUSION: These results are consistent
      with basic science data, suggesting that COL6A3 might contribute to adipose
      tissue inflammation.

PMID- 19837928
TI  - Independent confirmation of association between metabolic phenotypes of
      polycystic ovary syndrome and variation in the type 6 17beta-hydroxysteroid
      dehydrogenase gene.
AB  - CONTEXT: Few candidate genes for polycystic ovary syndrome (PCOS) are widely
      agreed upon largely due to lack of replication. Type 6 17beta-hydroxysteroid
      dehydrogenase (HSD17B6) gene expression is increased in PCOS ovarian theca.
      Previous genetic study of HSD17B6 reported significant association of rs898611
      with PCOS risk and metabolic phenotypes. OBJECTIVE: Our objective was to
      replicate association between polymorphisms in HSD17B6 and PCOS in a well
      characterized replication cohort. DESIGN: We conducted a case-control association
      study. SETTING: Subjects were recruited from reproductive endocrinology clinics;
      controls were recruited from the surrounding communities of the University of
      Alabama at Birmingham and Cedars-Sinai Medical Center in Los Angeles. Genotyping
      occurred at Cedars-Sinai Medical Center. PARTICIPANTS: Participants included 335
      White women with PCOS and 198 White controls. MAIN MEASUREMENTS: We assessed
      HSD17B6 genotype, PCOS status, and metabolic traits. RESULTS: The minor allele of
      rs898611 was not associated with PCOS; however, it was associated with increased
      body mass index (P = 0.031), increased fasting insulin (P = 0.008), decreased
      fasting glucose/insulin ratio (P = 0.038), and increased homeostasis model
      assessment of insulin resistance (HOMA-IR) (P = 0.021). rs10459247 and rs10876920
      were associated with increased fasting insulin (P = 0.031 and 0.019,
      respectively), and rs10876920 was also associated with increased HOMA-IR (P =
      0.046). Haplotype T-A-T-C was associated with reduced fasting insulin (P =
      0.046), and haplotype C-A-C-T was associated with increased body mass index (P =
      0.032). CONCLUSIONS: Although we did not replicate association between PCOS and
      rs898611, we replicated associations of this variant and others in HSD17B6 with
      metabolic traits. These replication data suggest a role for HSD17B6 in PCOS. How
      HSD17B6, an enzyme involved in steroid metabolism, may influence BMI and insulin
      resistance in PCOS remains to be determined.

PMID- 19837929
TI  - Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous
      and omental depots and after weight loss.
AB  - CONTEXT: Macrophages accumulate in adipose tissue and possibly participate in
      metabolic complications in obesity. Macrophage number varies with adipose tissue
      site and weight loss, but whether this is accompanied by phenotypic changes is
      unknown. OBJECTIVE: The objective of the study was to characterize the activation
      state of adipose tissue macrophages in human obesity. DESIGN/SETTING: We
      performed a single-center prospective study. PARTICIPANTS/INTERVENTIONS: Paired
      biopsies of sc and omental adipose tissue were obtained during gastric surgery in
      16 premenopausal obese women (aged 41.1 +/- 8.6 yr; body mass index 43.8 +/- 3.4
      kg/m(2)). Subcutaneous adipose tissue biopsies were obtained 3 months later in
      obese subjects and in 10 nonobese women (aged 43.3 +/- 3.5 yr; body mass index
      22.5 +/- 0.75 kg/m(2)). The number of macrophages stained with CD40, CD206, and
      CD163 surface markers was determined by immunochemistry. MAIN OUTCOMES: The
      number of CD40(+) macrophages significantly increased with obesity and in omental
      vs. sc adipose tissue in obese women. No significant changes in CD163(+) and
      CD206(+) macrophage counts was found with obesity and fat pad anatomical
      location. Three months after gastric surgery, the ratio of CD40(+) to CD206(+)
      macrophages was 2-fold lower than before surgery in the sc adipose tissue of
      obese subjects (P < 0.001) due to a concomitant decrease of CD40(+) and increase
      of CD206(+) macrophages counts. CONCLUSION: We suggest that the activation state
      of adipose tissue macrophages is weighted toward M1 over M2 status in obese
      subjects and switch to a less proinflammatory profile 3 months after gastric
      bypass.

PMID- 19837930
TI  - Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes
      mellitus.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is insulinotropic, but its effect on
      the alpha-cell is less clear. We investigated the dose-response relationship for
      GLP-1-induced glucagon suppression in patients with type 2 diabetes (T2DM) and
      healthy controls. DESIGN: Ten patients with T2DM (duration of DM, 4 +/- 1 yr;
      glycosylated hemoglobin, 7.1 +/- 0.3%) were studied on 2 d, with stepwise
      increasing GLP-1 infusions (0.25, 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1)) (d
      1) or saline (d 2) with plasma glucose (PG) clamped at fasting level. On d 3,
      patient PG was normalized overnight using a variable insulin infusion, followed
      by a 3-h GLP-1 infusion as on d 1. Ten healthy subjects were examined with the
      same protocol on d 1 and 2. RESULTS: We observed similar dose-dependent stepwise
      suppression of glucagon secretion in both patients and controls. Significant
      suppression was observed at a GLP-1 infusion rate of 0.25 pmol x kg(-1) x min(-1)
      (resulting in physiological plasma concentrations) as early as time 15 min in
      healthy controls and time 30 min in patients (d 1 and d 3). AUC for glucagon was
      significantly reduced on d 1 and 3 (1096 +/- 109 and 1116 +/- 108 3h x
      pmol/liter; P = NS) as compared to d 2 (1733 +/- 193 3h x pmol/liter; P < 0.01)
      in patients with T2DM. A similar reduction in AUC for glucagon was observed in
      healthy controls [1122 +/- 186 (d 1) vs. 1733 +/- 312 3h x pmol/liter (d 2); P <
      0.001]. CONCLUSIONS: The diabetic alpha-cell appears to be highly sensitive to
      the inhibitory action of GLP-1 both during high and near-normalized PG levels,
      but responds with a short, nevertheless significant delay.

PMID- 19837931
TI  - Dysregulation of glycogen synthase COOH- and NH2-terminal phosphorylation by
      insulin in obesity and type 2 diabetes mellitus.
AB  - CONTEXT: Insulin-stimulated glucose disposal is impaired in obesity and type 2
      diabetes mellitus (T2DM) and is tightly linked to impaired skeletal muscle
      glucose uptake and storage. Impaired activation of glycogen synthase (GS) by
      insulin is a well-established defect in both obesity and T2DM, but the underlying
      mechanisms remain unclear. DESIGN AND PARTICIPANTS: Insulin action was
      investigated in a matched cohort of lean healthy, obese nondiabetic, and obese
      type 2 diabetic subjects by the euglycemic-hyperinsulinemic clamp technique
      combined with muscle biopsies. Activity, site-specific phosphorylation, and
      upstream signaling of GS were evaluated in skeletal muscle. RESULTS: GS activity
      correlated inversely with phosphorylation of GS site 2+2a and 3a. Insulin
      significantly decreased 2+2a phosphorylation in lean subjects only and induced a
      larger dephosphorylation at site 3 in lean compared with obese subjects. The
      exaggerated insulin resistance in T2DM compared with obese subjects was not
      reflected by differences in site 3 phosphorylation but was accompanied by a
      significantly higher site 1b phosphorylation during insulin stimulation.
      Hyperphosphorylation of another Ca(2+)/calmodulin-dependent kinase-II target,
      phospholamban-Thr17, was also evident in T2DM. Dephosphorylation of GS by
      phosphatase treatment fully restored GS activity in all groups. CONCLUSIONS:
      Dysregulation of GS phosphorylation plays a major role in impaired insulin
      regulation of GS in obesity and T2DM. In obesity, independent of T2DM, this is
      associated with impaired regulation of site 2+2a and likely site 3, whereas the
      exaggerated insulin resistance to activate GS in T2DM is linked to
      hyperphosphorylation of at least site 1b. Thus, T2DM per se seems unrelated to
      defects in the glycogen synthase kinase-3 regulation of GS.

PMID- 19837932
TI  - Expression of progesterone receptor A form and its role in the interaction of
      progesterone with cortisol on cyclooxygenase-2 expression in amnionic
      fibroblasts.
AB  - CONTEXT: Human amnion fibroblasts produce abundant prostaglandins toward the end
      of gestation, which is believed to be one of the major events leading to
      parturition. Glucocorticoids have been shown to up-regulate cyclooxygenase-2 (COX
      2) expression, the crucial enzyme catalyzing prostaglandin synthesis, in human
      amnion fibroblasts. Although a major propregnancy hormone, the effect of
      progesterone and the associated progesterone receptor subtypes in the regulation
      of both basal and glucocorticoid-induced COX-2 expression in human amnion
      fibroblasts have not been resolved. METHODS AND RESULTS: Cultured human amnion
      fibroblasts prepared from the fetal membranes at term pregnancy without labor
      mainly expressed the progesterone receptor A form (PRA). Inhibition of endogenous
      progesterone production with trilostane or knockdown of PRA expression with small
      interfering RNA significantly enhanced the glucocorticoid receptor (GR)-mediated
      COX-2 induction by cortisol, whereas overexpression of PRA attenuated the
      induction by cortisol. Co-immunoprecipitation assay revealed PRA in the GR
      protein complex. Although exogenous progesterone did not alter COX-2 expression
      under basal conditions, it attenuated cortisol-induced COX-2 expression at
      concentrations about 10- to 50-fold higher, which might be achieved by
      competition with cortisol for GR. CONCLUSIONS: We demonstrated in this study that
      endogenous progesterone might counteract the induction of prostaglandin synthesis
      by cortisol via PRA transdominant repression of GR function, whereas high levels
      of progesterone might further inhibit the induction by cortisol via competitive
      binding to GR in human amnion fibroblasts. These inhibitory actions of
      progesterone and PRA on glucocorticoids and GR may partly explain the
      inconsistent effects of glucocorticoids on parturition in humans.

PMID- 19837933
TI  - Genetic predisposition to elevated serum thyrotropin is associated with
      exceptional longevity.
AB  - CONTEXT: Exceptional longevity is associated with raised serum TSH. OBJECTIVE:
      The aim of this study was to examine whether offspring of people with exceptional
      longevity have elevated serum TSH and whether specific single nucleotide
      polymorphisms (SNPs) in the TSH-B gene and TSH receptor (TSHR) gene are
      associated with this phenotype. DESIGN/SETTING/PATIENTS: We measured serum TSH
      and free T(4) in Ashkenazi Jewish centenarians (n = 232; median age, 97 yr),
      their offspring (n = 366; median age, 69 yr), and age-matched controls without
      familial longevity (n = 163; median age, 70 yr). We determined TSH heritability,
      its distribution, and association with SNPs in the TSH-B and TSHR genes. RESULTS:
      Offspring had higher median serum TSH [1.68 mIU/liter (97.5% confidence interval,
      0.65 to 4.79 mIU/liter)], compared to controls [1.50 mIU/liter (97.5% confidence
      interval, 0.63 to 3.93 mIU/liter); P = 0.02], with estimated heritability of 0.33
      (P = 0.004). Allele frequency of two SNPs in the promoter/enhancer region of TSHR
      gene, associated with increased serum TSH, was higher in centenarians and their
      offspring compared to controls (rs10149689 G allele frequency, 0.57 and 0.53 vs.
      0.48; P = 0.001 and P = 0.08; odds ratio, 1.56 and 1.22, respectively; and
      rs12050077 A allele frequency, 0.57 and 0.53 vs. 0.46; P = 0.0001 and P = 0.01;
      odds ratio, 1.68 and 1.32, respectively). Linkage disequilibrium between the two
      SNPs was high (r(2) = 0.95), suggesting interaction between them. Furthermore, GA
      haplotype frequency was significantly higher among centenarians and offspring
      compared to controls (0.57 and 0.53 vs. 0.46; P = 0.0001 and P = 0.01,
      respectively). CONCLUSIONS: A heritable phenotype characterized by raised serum
      TSH is associated with human longevity. Carriers of rs12050077 and rs10149689
      SNPs in the TSHR have higher serum TSH, possibly contributing to decreased
      thyroid function and longevity.

PMID- 19837934
TI  - The glucagon test in the diagnosis of growth hormone deficiency in children with
      short stature younger than 6 years.
AB  - CONTEXT: Few studies have addressed the diagnostic role of the glucagon test in
      children with suspected GH deficiency (GHD). OBJECTIVE: The objective of the
      study was to investigate the diagnostic value of the glucagon test as an
      alternative test to insulin tolerance test (ITT) and arginine in GHD children
      younger than 6 yr. DESIGN AND SETTING: This study was conducted in two pediatric
      endocrinology centers. PATIENTS AND METHODS: Forty-eight children (median age 4.2
      yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and
      arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter,
      respectively) underwent a glucagon stimulation test. Magnetic resonance imaging
      showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior
      pituitary hypoplasia in seven, and structural hypothalamic-pituitary
      abnormalities in 17. RESULTS: Median GH peak response to glucagon (13.5
      microg/liter) was significantly higher than that observed after ITT and arginine
      (P < 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects
      (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without
      significant clinical or biochemical differences between the two groups. Median GH
      peak after glucagon was similar between patients with multiple pituitary hormone
      deficiency and those with isolated GHD and between subjects with and without
      structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak
      after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P <
      0.0001). CONCLUSIONS: This study shows that glucagon has an effective GH
      releasing activity and can be used to evaluate somatotroph function in young
      children with short stature. Normative data for this test in young children need
      to be established before its use in clinical practice.

PMID- 19837936
TI  - Six new mutations of the thyroglobulin gene discovered in taiwanese children
      presenting with thyroid dyshormonogenesis.
AB  - BACKGROUND: Thyroglobulin (TG) defect is a rare cause of congenital
      hypothyroidism. Although only 44 mutations of the human TG gene have been
      identified, we have suspected a TG defect in 38% of Taiwan Chinese
      children/adolescents presenting with moderate or severe thyroidal
      dyshormonogenesis. STUDY OBJECTIVE: The aim of the study is to report the
      discovery of new TG gene mutations and associated clinical manifestations of the
      defective TG protein. PATIENTS AND RESULTS: In seven patients from six families,
      we detected six new TG gene mutations, including c.1348delT, p.R432X (c.1351C>T),
      g.IVS3 + 2T>G, c.1712delT, p.Q1765X (c.5350C>T), and c.6047delA. The c.1348delT
      and p.R432X mutations were the most common, detected in 33 and 25%, respectively,
      of alleles studied. Haplotype analysis suggested that the c.1348delT and g.IVS3 +
      2T>G mutations are due to founder effects, whereas p.R432X is probably due to
      independently recurrent de novo mutations. mRNA transcript of the g.IVS3 + 2T>G
      mutant, detected in whole blood by reverse transcription-nested PCR, showed
      skipping of exon 3 (98-bp deletion) and a frameshift, with a terminal signal
      after 17 altered amino acid residues. CONCLUSIONS: TG defects have an important
      role in severe thyroidal dyshormonogenesis (pretreatment, or after a 3-wk T(4)
      withdrawal, plasma T(4) < or = 30 nmol/liter) in Taiwanese. Its genetic
      characteristics are markedly different from those described in other populations
      presenting with mutations of the TG gene.

PMID- 19837935
TI  - A molecular basis for variation in clinical severity of isolated growth hormone
      deficiency type II.
AB  - CONTEXT: Dominant-negative GH1 mutations cause familial isolated growth hormone
      deficiency type II (IGHD II), which is characterized by GH deficiency, occasional
      multiple anterior pituitary hormone deficiencies, and anterior pituitary
      hypoplasia. The basis of the variable expression and progression of IGHD II among
      relatives who share the same GH1 mutation is poorly understood. OBJECTIVE: We
      hypothesized that the cellular ratios of mutant/normal GH1 transcripts would
      correlate with the severity of the IGHD II phenotype. We determined the relative
      amounts of mutant and normal GH1 transcripts in cell lines and correlated
      transcript ratios with severity. DESIGN AND PATIENTS: Members of the same IGHD II
      kindred were genotyped for the GH1 E3+1 G/A mutation by DNA sequencing. Ratios of
      their 17.5-kDa (mutant)/22-kDa (normal) GH1 transcripts were determined in
      cultured lymphocytes (CLs), and these ratios were correlated with height sd
      scores obtained before GH replacement therapy. RESULTS: Ratios of 17.5-/22-kDa
      GH1 transcripts in CLs from family members with the same IGHD II mutation
      correlated with differences in their height SD scores. CONCLUSIONS: Our findings
      suggest that expression levels of both the mutant and normal GH1 allele are
      important in the pathogenesis of IGHD II, that the ratio of mutant/normal
      transcripts may be a predictive marker of the penetrance and severity of IGHD II,
      and that CLs may be useful as surrogates to study GH1 transcript expression of
      subjects whose anterior pituitary cells are not available.

PMID- 19837937
TI  - Reassessment of the growth hormone status in young adults with childhood-onset
      growth hormone deficiency: reappraisal of insulin tolerance testing.
AB  - CONTEXT: The 2007 Consensus Statement suggested a peak GH cutoff to insulin
      tolerance test (ITT) of less than 6 microg/liter in the diagnosis of permanent GH
      deficiency (GHD) in young adults with childhood-onset GHD (COGHD), although
      further validation was recommended. OBJECTIVE: The aim of the study was to
      evaluate the accuracy of ITT, mean 12-h spontaneous nocturnal GH (SNGH), and IGF
      I in the definition of permanent GHD. DESIGN AND SETTING: The study was conducted
      in two Pediatric Endocrinology Centers. PATIENTS AND METHODS: ITT, 12-h SNGH, and
      IGF-I were evaluated as single or combined tests in 79 subjects with COGHD
      (median age, 18.0 yr). The cohort consisted of 48 subjects with isolated GHD or
      one additional pituitary defect and normal MRI or anterior pituitary hypoplasia
      (group LLGHD, low likelihood GHD), and 31 subjects with structural hypothalamic
      pituitary abnormalities or multiple pituitary hormone deficiencies (group HLGHD,
      high likelihood GHD). RESULTS: Receiver operating characteristic analysis showed
      the best diagnostic accuracy for peak GH cutoffs to ITT of 5.62 microg/liter or
      less [sensitivity, 77.4%; specificity, 93.8%; area under the curve (AUC) = 0.92],
      mean 12-h SNGH of 1.20 microg/liter or less (sensitivity, 90.3%; specificity,
      89.6%; AUC = 0.93), and IGF-I of -2.83 sd score or less (sensitivity, 80.7%;
      specificity, 95.7%; AUC = 0.93). Seven patients in group HLGHD showed a peak GH
      to ITT above 5.62 microg/liter, but a median IGF-I that was significantly lower
      than that of group LLGHD (-3.30 vs. -0.73 sd score; P = 0.0001). Peak GH to ITT
      of 3.6 microg/liter or less and arginine of 3.1 microg/liter or less at childhood
      diagnosis can predict a future permanent GHD condition. CONCLUSIONS: The adopted
      peak GH to ITT below 5.62 microg/liter is an accurate diagnostic cutoff point for
      HLGHD in young adults with COGHD. In addition, IGF-I is a reliable marker
      providing information about the severity of GHD. Careful follow-up is required
      for subjects with discordant ITT and IGF-I results.

PMID- 19837938
TI  - Efficacy and safety of long-term continuous growth hormone treatment in children
      with Prader-Willi syndrome.
AB  - BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body
      composition and impaired growth. Short-term GH treatment has beneficial effects.
      OBJECTIVES: The aim of the study was to investigate effects of long-term
      continuous GH treatment on body composition, growth, bone maturation, and safety
      parameters. SETTING: We conducted a multicenter prospective trial. DESIGN: Fifty
      five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr
      of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one
      center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray
      absorptiometry, height, weight, head circumference, bone age, blood pressure, and
      fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin,
      total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd
      scores (SDS) were calculated according to Dutch and PWS reference values (SDS and
      SDS(PWS)). RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P
      < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but
      returned to baseline values the second year and remained unchanged thereafter.
      Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P <
      0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/-
      1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and
      the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and
      2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone
      maturation, blood pressure, glucose homeostasis, and serum lipids. CONCLUSIONS:
      Our study in children with PWS shows that 4 yr of continuous GH treatment (1
      mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing
      LBMSDS and head circumference SDS and normalizes heightSDS without adverse
      effects. Thus, long-term continuous GH treatment is an effective and safe therapy
      for children with PWS.

PMID- 19837939
TI  - Chorionic gonadotropin stimulation of angiogenesis and pericyte recruitment.
AB  - CONTEXT: During the periimplantation period, human chorionic gonadotropin (hCG)
      plays a key role by increasing the uterine blood flow through uterine vessel
      vasodilatation but also through angiogenesis. Indeed, we previously demonstrated
      that hCG contributes to endothelial cell recruitment and vessel formation.
      OBJECTIVE: In this study, hCG was proposed as an arteriogenic factor that could
      promote perivascular cell recruitment and vessel stabilization. DESIGN: The
      aortic ring assay, a three-dimensional ex vivo angiogenesis system mimicking all
      the steps of the angiogenesis process was used to study the impact of hCG on
      pericyte recruitment and vessel maturation. SETTING: The study was conducted at a
      university hospital laboratory. MAIN OUTCOME MEASURES: Perivascular cell
      proliferation, migration, and apposition were quantified by computerized image
      analysis. RESULTS: Physiological concentrations of hCG (10-400 IU/ml)
      significantly enhanced pericyte sprouting and migration and gave rise to the
      maturation and coverage of endothelial capillaries. In a three-dimensional
      coculture model of endothelial and perivascular cells, hCG enhanced vessel tube
      formation and endothelial/mural cell adhesion. In addition, hCG stimulated the
      proliferation of human umbilical vein endothelial cells and smooth muscle cells.
      The specificity of these effects was determined by using an anti-hCG blocking
      antibody. Signaling pathways implicated on this hCG effect is protein kinase A
      and phospholipase C/protein kinase C dependent for the proliferative effect but
      only phospholipase C/protein kinase C for the migrative process. CONCLUSIONS: Our
      findings highlight a novel paracrine role of this early embryonic signal in
      vessel maturation by stimulating perivascular cell recruitment, migration, and
      proliferation.

PMID- 19837940
TI  - Array comparative genomic hybridization profiling analysis reveals
      deoxyribonucleic acid copy number variations associated with premature ovarian
      failure.
AB  - INTRODUCTION: Premature ovarian failure (POF) is defined by amenorrhea of at
      least 4- to 6-month duration, occurring before 40 yr of age, with two FSH levels
      in the postmenopausal range. Its etiology remains unknown in more than 80% of
      cases. Standard karyotypes, having a resolution of 5-10 Mb, have identified
      critical chromosomal regions, mainly located on the long arm of the X chromosome.
      Array comparative genomic hybridization (a-CGH) analysis is able to detect
      submicroscopic chromosomal rearrangements with a higher genomic resolution. We
      searched for copy number variations (CNVs), using a-CGH analysis with a
      resolution of approximately 0.7 Mb, in a cohort of patients with POF. PATIENTS
      AND METHODS: We prospectively included 99 women. Our study included a
      conventional karyotype and DNA microarrays comprising 4500 bacterial artificial
      chromosome clones spread on the entire genome. RESULTS: Thirty-one CNVs have been
      observed, three on the X chromosome and 28 on autosomal chromosomes. Data have
      been compared to control populations obtained from the Database of Genomic
      Variants (http://projects.tcag.ca/variation). Eight statistically significantly
      different CNVs have been identified in chromosomal regions 1p21.1, 5p14.3,
      5q13.2, 6p25.3, 14q32.33, 16p11.2, 17q12, and Xq28. CONCLUSION: We report the
      first study of CNV analysis in a large cohort of Caucasian POF patients. In the
      eight statistically significant CNVs we report, we found five genes involved in
      reproduction, thus representing potential candidate genes in POF. The current
      study along with emerging information regarding CNVs, as well as data on their
      potential association with human diseases, emphasizes the importance of assessing
      CNVs in cohorts of POF women.

PMID- 19837941
TI  - The stability of metabolic syndrome in children and adolescents.
AB  - CONTEXT: Some studies suggest the presence of metabolic syndrome before adulthood
      may identify those at high risk for later cardiovascular morbidity, but there are
      few data examining the reliability of pediatric metabolic syndrome. OBJECTIVE: To
      examine the short- and long-term stability of pediatric metabolic syndrome.
      DESIGN: Metabolic syndrome was defined as having at least three of the following:
      waist circumference, blood pressure, and fasting serum triglycerides in the 90th
      or higher percentile for age/sex; high-density lipoprotein-cholesterol 10th or
      lower percentile for age/sex; and fasting serum glucose of at least 100 mg/dl.
      Short-term metabolic syndrome stability (repeated measurements within 60 d) was
      assessed in obese youth ages 6-17 yr. Long-term metabolic syndrome stability
      (repeated measurements more than 1.5 yr apart) was studied in 146 obese and
      nonobese children age 6-12 yr at baseline. PATIENTS AND SETTING: Convenience
      samples of obese and nonobese youth ages 6-17 yr participating in research
      studies were collected at a clinical research hospital. RESULTS: Short-term
      metabolic syndrome stability (repeat measurements performed 19.7 +/- 13.1 d
      apart) was assessed in 220 children. The diagnosis of metabolic syndrome was
      unstable in 31.6% of cases. At their short-term follow-up visit, incidence of
      metabolic syndrome among participants who did not have metabolic syndrome at
      baseline was 24%. In the long term (repeat measurements performed 5.6 +/- 1.9 yr
      apart), the diagnosis of metabolic syndrome was unstable in 45.5% of cases.
      CONCLUSIONS: Cutoff-point-based definitions for pediatric metabolic syndrome have
      substantial instability in the short and long term. The value of making a cutoff
      point-based diagnosis of metabolic syndrome during childhood or adolescence
      remains in question.

PMID- 19837942
TI  - Skeletal muscle lipogenic protein expression is not different between lean and
      obese individuals: a potential factor in ceramide accumulation.
AB  - CONTEXT: Skeletal muscle lipid content is increased in obesity. Recent evidence
      suggests that fatty acid (FA) storage as triacylglycerol (TAG) represents a
      metabolically safe pool compared to the more bioactive diacylglycerol (DAG) and
      ceramide. OBJECTIVE/DESIGN: The purpose of this study was to compare the
      expression of lipogenic proteins and ceramide and DAG content in skeletal muscle
      of lean and obese humans. We hypothesized that lipogenic protein expression would
      be increased in obese to facilitate the storage of excess FA as TAG.
      PARTICIPANTS: Eighteen lean (BMI < or = 26 kg/m(2)) and 15 obese (BMI > 29
      kg/m(2)) women participated in this study. RESULTS: There was no difference in
      the expression of any lipogenic (stearoyl-CoA desaturase-1, stearoyl retinol
      binding protein-1c, mitochondrial glycerol-3-phosphate acyltransferase,
      diacylglycerol acyltransferase-1) or sphingolipid proteins measured between lean
      and obese humans. Total ceramide was increased in muscle from obese humans (lean
      vs. obese, 529.4 +/- 54.8 vs. 672.4 +/- 57.4 nmol/g; P < 0.05), but there was no
      difference in total DAG content (lean vs. obese, 2244.1 +/- 278.2 vs. 1941.4 +/-
      165.0 nmol/g). Content of protein phosphatase 2A, a ceramide target, was
      increased in muscle of obese humans (P < 0.05). CONCLUSIONS: We propose that in
      muscle of obese humans there is an insufficient lipogenic response to the lipid
      oversupply, allowing more FA to be stored as reactive lipid species, particularly
      ceramide, potentially contributing to subsequent metabolic complications.

PMID- 19837943
TI  - E2F1 induces pituitary tumor transforming gene (PTTG1) expression in human
      pituitary tumors.
AB  - Rb/E2F is dysregulated in murine and human pituitary tumors. Pituitary tumor
      transforming gene (PTTG1), a securin protein, is required for pituitary
      tumorigenesis, and PTTG1 deletion attenuates pituitary tumor development in Rb(+/
      ) mice. E2F1 and PTTG1 were concordantly overexpressed in 29 of 46 Rb(+/-) murine
      pituitary tissues and also in 45 of 80 human pituitary tumors (P < 0.05). E2F1
      specifically bound the hPTTG1 promoter as assessed by chromatin
      immunoprecipitation and biotin-streptavidin pull-down assay, indicating that
      hPTTG1 may act as a direct E2F1 target. Transfection of E2F1 and its partner DP1
      dose-dependently activated hPTTG1 transcription up to 3-fold in p53-devoid H1299
      cells but not in p53-replete HCT116 cells. E2F1 overexpression enhanced
      endogenous hPTTG1 mRNA and protein levels up to 3-fold in H1299 cells. The
      presence of endogenous p53/p21 constrained the induction, whereas knocking down
      either p53 or p21 in HCT116 cells restored E2F1-induced hPTTG1 transactivation
      and expression. Moreover, suppressing Rb by small interfering RNA concordantly
      elevated E2F1 and hPTTG1 protein levels. In contrast, transfection of E2F1 small
      interfering RNA lowered hPTTG1 levels 24 h later in HCT116 than in H1299 cells,
      indicating that p53 delays E2F1 action on hPTTG1. These results elucidate a
      mechanism for abundant tumor hPTTG1 expression, whereby Rb inactivation releases
      E2F1 to induce hPTTG1. This signaling pathway may underlie the requirement of
      PTTG1 for pituitary tumorigenesis.

PMID- 19837944
TI  - Minireview: modulation of hormone receptor signaling by dietary anticancer
      indoles.
AB  - Indole-3-carbinol and its diindole condensation product 3-3'-diindolylmethane are
      dietary phytochemicals that have striking anticarcinogenic properties in human
      cancer cells. Molecular, cellular, physiological, and clinical studies have
      documented that both indole-3-carbinol and 3-3'-diindolylmethane have potent
      endocrine modulating activities through a myriad of mechanisms. The focus of this
      review is to discuss the evidence that directly links the anticancer actions of
      these two indole compounds to the control of steroid receptor and growth factor
      receptor signaling.

PMID- 19837946
TI  - Does conduit artery diameter vary according to the anthropometric characteristics
      of children or men?
AB  - Arterial measurements are commonly undertaken to assess acute and chronic
      adaptations to exercise. Despite the widespread adoption of scaling practices in
      cardiac research, the relevance of scaling for body size and/or composition has
      not been addressed for arterial measures. We therefore investigated the
      relationships between brachial artery diameter and body composition in 129
      children aged 9 to 10 yr (75 girls and 54 boys), and 50 men aged 16-49 yr. Body
      composition variables (total, lean, and fat mass in the whole body, arm, and
      forearm) were assessed by dual-energy X-ray absorptiometry, and brachial artery
      diameter was measured using high-resolution ultrasound. Bivariate correlations
      were performed, and arterial diameter was then scaled using simple ratios (y/x)
      and allometric approaches after log-log least squares linear regression and
      production of allometric exponents (b) and construction of power function ratios
      (y/xb). Size independence was checked via bivariate correlations (x:y/x; x:y/xb).
      As a result, significant correlations existed between brachial artery diameter
      and measures of body mass and lean mass in both cohorts (r=0.21-0.48, P<0.05).
      There were no significant relationships between diameter and fat mass. All b
      exponents were significantly different from 1 (0.08-0.50), suggesting that simple
      ratio scaling approaches were likely to be flawed. This was confirmed when ratio
      scaling produced negative residual size correlations, whereas allometric scaling
      produced size-independent indexes (r=0.00 to 0.03, P>0.05). In conclusion, when
      between- or within-group comparisons are performed under circumstances where it
      is important to control for differences in body size or composition, allometric
      scaling of artery diameter should be adopted rather than ratio scaling. Our data
      also suggest that scaling for lean or total mass may be more appropriate than
      scaling for indexes of fat mass.

PMID- 19837945
TI  - Role of phospholipase D in parathyroid hormone type 1 receptor signaling and
      trafficking.
AB  - The role of phospholipase D (PLD) in the regulation of the traffic of the PTH
      type 1 receptor (PTH1R) was studied in Chinese hamster ovary cells stably
      transfected with a human PTH1R (CHO-R3) and in rat osteosarcoma 17/2.8 (ROS)
      cells. PTH(1-34) increased total PLD activity by 3-fold in CHO-R3 cells and by 2
      fold in ROS cells. Overexpression of wild-type (WT) PLD1 and WT-PLD2 increased
      basal PLD activity in CHO-R3 but not in ROS cells. Ligand-stimulated PLD activity
      greatly increased in CHO-R3 cells transfected with WT-PLD1 and WT-PLD2. However,
      only WT-PLD2 expression increased PTH-dependent PLD activity in ROS cells.
      Expression of the catalytically inactive mutants R898K-PLD1 (DN-PLD1) and R758K
      PLD2 (DN-PLD2) inhibited ligand-dependent PLD activity in both cell lines. PTH(1
      34) induced internalization of the PTH1R with a concomitant increase in the
      colocalization of the receptor with PLD1 in intracellular vesicles and in a
      perinuclear, ADP ribosylation factor-1-positive compartment. The distribution of
      PLD1 and PLD2 remained unaltered after PTH treatment. Expression of DN-PLD1 had a
      small effect on endocytosis of the PTH1R; however, DN-PLD1 prevented accumulation
      of the PTH1R in the perinuclear compartment. Expression of DN-PLD2 significantly
      retarded ligand-induced PTH1R internalization in both cell lines. The
      differential effects of PLD1 and PLD2 on receptor traffic were confirmed using
      isoform-specific short hairpin RNA constructs. We conclude that PLD1 and PLD2
      play distinct roles in regulating PTH1R traffic; PLD2 primarily regulates
      endocytosis, whereas PLD1 regulates receptor internalization and intracellular
      receptor traffic.

PMID- 19837947
TI  - Differential phosphoinositide 3-kinase signaling: implications for PTCA?

PMID- 19837948
TI  - Ryanodine receptor Ca2+ sensitivity and excitation-contraction coupling in
      muscular dystrophy and heart failure: similar and yet different.

PMID- 19837949
TI  - Right ventricular free wall pacing improves cardiac pump function in severe
      pulmonary arterial hypertension: a computer simulation analysis.
AB  - In pulmonary arterial hypertension (PAH), duration of myofiber shortening is
      prolonged in the right ventricular (RV) free wall (RVfw) compared with that in
      the interventricular septum and left ventricular free wall. This interventricular
      mechanical asynchrony eventually leads to right heart failure. We investigated by
      computer simulation whether, in PAH, early RVfw pacing may improve
      interventricular mechanical synchrony and, hence, cardiac pump function. A
      mathematical model of the human heart and circulation was used to simulate left
      ventricular and RV pump mechanics and myofiber mechanics. First, we simulated
      cardiovascular mechanics of a healthy adult at rest. Size and mass of heart and
      blood vessels were adapted so that mechanical tissue load was normalized. Second,
      compensated PAH was simulated by increasing mean pulmonary artery pressure to 32
      mmHg while applying load adaptation. Third, decompensated PAH was simulated by
      increasing mean pulmonary artery pressure further to 79 mmHg without further
      adaptation. Finally, early RVfw pacing was simulated in severely decompensated
      PAH. Time courses of circumferential strain in the ventricular walls as simulated
      were similar to the ones measured in healthy subjects (uniform strain patterns)
      and in PAH patients (prolonged RVfw shortening). When simulating pacing in
      decompensated PAH, RV pump function was best upon 40-ms RVfw preexcitation, as
      evidenced by maximal decrease of RV end-diastolic volume, reduced RVfw myofiber
      work, and most homogeneous distribution of workload over the ventricular walls.
      Thus our simulations indicate that, in decompensated PAH, RVfw pacing may improve
      RV pump function and may homogenize workload over the ventricular walls.

PMID- 19837951
TI  - Physiological roles of endogenous ouabain in normal rats.
AB  - Endogenous ouabain (EO)-like compounds are synthesized in and released from the
      adrenal gland. Although EO has been implicated in several pathological states
      such as hypertension and heart and kidney failure, its physiological roles in
      normal animal have not been elucidated. To address this issue, we studied the
      effects of reduction in plasma EO resulting from antiouabain antibody
      administration. Normal rats were treated for 28 days with antiouabain antibodies
      or rabbit IgG as control. Infusions were delivered through a jugular vein cannula
      by osmotic pumps, and blood pressure was monitored by tail-cuff plethysmography.
      The animals were housed in metabolic cages to measure water and food consumption
      and urine excretion. After 28 days, the thoracic aorta was isolated and used to
      study phenylephrine-induced contraction and atrial natriuretic peptide (ANP)
      induced vasorelaxation. The adrenal gland cortex was enlarged in the antiouabain
      antibody-treated rats. Moreover, on the second day of treatment, there was a
      significant transient reduction in natriuresis in the antiouabain antibody
      treated rats, suggesting that EO is a natriuretic hormone. Reduction in
      natriuresis was also observed when EO levels were reduced by active immunization
      resulting from sequential injection of ouabain-albumin. Furthermore, following 28
      days of treatment, the response to phenylephrine was significantly lowered and
      that to ANP was significantly increased in aortic rings from antiouabain antibody
      treated rats. These findings show for the first time that circulatory ouabain
      plausibly originating in the adrenal has physiological roles controlling
      vasculature tone and sodium homeostasis in normal rats.

PMID- 19837950
TI  - Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide
      bioavailability, and early atherosclerotic plaque formation in ApoE-/- mice.
AB  - The Nox family NADPH oxidases are reactive oxygen species (ROS)-generating
      enzymes that are strongly implicated in atherogenesis. However, no studies have
      examined which Nox isoform(s) are involved. Here we investigated the role of the
      Nox2-containing NADPH oxidase in atherogenesis in apolipoprotein E-null (ApoE(-/
      )) mice. Wild-type (C57Bl6/J), ApoE(-/-), and Nox2(-/y)/ApoE(-/-) mice were
      maintained on a high-fat (21%) diet from 5 wk of age until they were 12 or 19 wk
      old. Mice were euthanized and their aortas removed for measurement of Nox2
      expression (Western blot analysis and immunohistochemistry), ROS production (L012
      enhanced chemiluminescence), nitric oxide (NO) bioavailability (contractions to
      N(omega)-nitro-L-arginine), and atherosclerotic plaque development along the
      aorta and in the aortic sinus. Nox2 expression was upregulated in the aortic
      endothelium of ApoE(-/-) mice before the appearance of lesions, and this was
      associated with elevated ROS levels. Within developing plaques, macrophages were
      also a prominent source of Nox2. The absence of Nox2 in Nox2(-/y)/ApoE(-/-)
      double-knockout mice had minimal effects on plasma lipids or lesion development
      in the aortic sinus in animals up to 19 wk of age. However, an en face
      examination of the aorta from the arch to the iliac bifurcation revealed a 50%
      reduction in lesion area in Nox2(-/y)/ApoE(-/-) versus ApoE(-/-) mice, and this
      was associated with a marked decrease in aortic ROS production and an increased
      NO bioavailability. In conclusion, this is the first demonstration of a role for
      Nox2-NADPH oxidase in vascular ROS production, reduced NO bioavailability, and
      early lesion development in ApoE(-/-) mice, highlighting this Nox isoform as a
      potential target for future therapies for atherosclerosis.

PMID- 19837952
TI  - Caspase-mediated protein kinase C-delta cleavage is necessary for apoptosis of
      vascular smooth muscle cells.
AB  - Apoptotic death of vascular smooth muscle cells (SMCs) is a prominent feature of
      blood vessel remodeling and various vascular diseases. We have previously shown
      that protein kinase C-delta (PKC-delta) plays a critical role in SMC apoptosis.
      In this study, we tested the importance of PKC-delta proteolytic cleavage and
      tyrosine phosphorylation within the apoptosis pathway. Using hydrogen peroxide as
      a paradigm for oxidative stress, we showed that proteolytic cleavage of PKC-delta
      occurred in SMCs that underwent apoptosis, while tyrosine phosphorylation was
      detected only in necrotic cells. Furthermore, using a peptide (z-DIPD-fmk) that
      mimics the caspase-3 binding motif within the linker region of PKC-delta, we were
      able to prevent the cleavage of PKC-delta, as well as apoptosis. Inhibition of
      PKC-delta with rottlerin or small-interfering RNA diminished caspase-3 cleavage,
      caspase-3 activity, cleavage of poly (ADP-ribose) polymerase, cleavage of PKC
      delta, and DNA fragmentation, confirming the previously reported role of PKC
      delta in initiation of apoptosis. In contrast, z-DIPD-fmk markedly diminished
      caspase-3 activity, cleavage of PKC-delta, and DNA fragmentation without
      affecting cleavage of caspase-3 and poly (ADP-ribose) polymerase. Taken together,
      our data suggest that caspase-3-mediated PKC-delta cleavage underlies SMC
      apoptosis induced by oxidative stress, and that PKC-delta acts both upstream and
      downstream of caspase-3.

PMID- 19837953
TI  - Inhibition of matrix metalloproteinase activity in vivo protects against vascular
      hyporeactivity in endotoxemia.
AB  - Persistent arterial hypotension is a hallmark of sepsis and is believed to be
      caused, at least in part, by excess nitric oxide (NO). NO can combine with
      superoxide to produce peroxynitrite, which activates matrix metalloproteinases
      (MMPs). Whether MMP inhibition in vivo protects against vascular hyporeactivity
      induced by endotoxemia is unknown. Male Sprague-Dawley rats were administered
      either bacterial lipopolysaccharide (LPS, 4 mg/kg ip) or vehicle (pyrogen-free
      water). Later (30 min), animals received the MMP inhibitor doxycycline (4 mg/kg
      ip) or vehicle (pyrogen-free water). After LPS injection (6 h), animals were
      killed, and aortas were excised. Aortic rings were mounted in organ baths, and
      contractile responses to phenylephrine or KCl were measured. Aortas and plasma
      were examined for MMP activity by gelatin zymography. Aortic MMP and inducible
      nitric oxide synthase (iNOS) were examined by immunoblot and/or
      immunohistochemistry. Doxycycline prevented the LPS-induced development of ex
      vivo vascular hyporeactivity to phenylephrine and KCl. iNOS protein was
      significantly upregulated in aortic homogenates from endotoxemic rats;
      doxycycline did not alter its level. MMP-9 activity was undetectable in aortic
      homogenates from LPS-treated rats but significantly upregulated in the plasma;
      this was attenuated by doxycycline. Plasma MMP-2 activities were unchanged by
      LPS. Specific MMP-2 activity was increased in aortas from LPS-treated rats. This
      study demonstrates the in vivo protective effect of the MMP inhibitor doxycycline
      against the development of vascular hyporeactivity in endotoxemic rats.

PMID- 19837954
TI  - Hwp1 and related adhesins contribute to both mating and biofilm formation in
      Candida albicans.
AB  - Candida albicans Hwp1, Hwp2, and Rbt1 are related cell wall proteins expressed
      during the programs of sexual differentiation and filamentous growth. In this
      study, we compare strains lacking either single factors or a combination of these
      genes, and we demonstrate distinct but overlapping roles in mating and biofilm
      formation.

PMID- 19837955
TI  - A call to action.

PMID- 19837956
TI  - The legacy of pediatric oncology nursing in advancing survivorship research and
      clinical care.
AB  - Today, the growing population of cancer survivors, both pediatric and adult,
      along with the accumulated weight of data characterizing late and lingering
      effects of cancer and its treatment are attracting attention in the form of
      reports, conferences, publications and media coverage.The emphasis on
      survivorship research and outcomes-based clinical care began with pediatric
      oncology, and pediatric oncology nurses have been at the forefront of
      survivorship clinical care, research, and education for more than 30 years.This
      article highlights these contributions to the body of survivorship knowledge and
      quality of care, as well as areas of ongoing challenge and future directions
      suggested by thought leaders in our specialty. Key contributions are examined
      decade by decade and against the six recommendations for health care policy and
      practice delineated in the two recent IOM survivorship reports: evidence-based
      guidelines for follow-up care, standards and models of care, increasing awareness
      of late effects and needed follow-up care, improving professional education and
      training, improving access to care for survivors, and increasing research to
      prevent or manage late effects.

PMID- 19837957
TI  - Brain tumor survivors speak out.
AB  - Although progress has been made in the treatment of childhood brain tumors,work
      remains to understand the complexities of disease, treatment, and contextual
      factors that underlie individual differences in outcome. A combination of both an
      idiographic approach (incorporating observations made by adult survivors of
      childhood brain tumors) and a nomothetic approach (reviewing the literature for
      brain tumor survivors as well as childhood cancer survivors) is presented. Six
      areas of concern are reviewed from both an idiographic and nomothetic
      perspective, including social/emotional adjustment, insurance, neurocognitive
      late effects, sexuality and relationships, employment, and where survivors
      accessed information about their disease and treatment and possible late effects.
      Guidelines to assist health care professionals working with childhood brain tumor
      survivors are offered with the goal of improving psychosocial and neurocognitive
      outcomes in this population.

PMID- 19837958
TI  - Transitioning survivors of central nervous system tumors: challenges for
      patients, families, and health care providers.
AB  - Survivors of central nervous system tumors (SCNST) are a growing group of cancer
      survivors who require risk-based, long-term health care due to the chemotherapy,
      surgery, and radiation they have received.Although treatment strategies are being
      developed to reduce morbidity and mortality, ultimately this subgroup of
      pediatric cancer survivors often faces moderate to severe late effects of their
      treatment.As a result, they will need lifelong health care that includes risk
      based health care due to cancer treatment exposures as well as primary adult
      health care, including primary and secondary preventative care. The best way to
      accomplish lifelong health care for SCNST as they enter adulthood is not clearly
      defined. In this article, the authors plan to (1) present an overview of the
      complexities of health care problems that make transition challenging for SCNST;
      (2) review the evolving transition literature; (3) explore the barriers to
      successful transition; (4) discuss methods to facilitate transition; (5) describe
      approaches, strategies, and models for survivorship care in SCNST; (6) present
      issues for consideration when transitioning SCNST; and (7) provide information on
      transition-related resources.

PMID- 19837959
TI  - Endocrine late effects in survivors of pediatric brain tumors.
AB  - Central nervous system tumors are the most common solid tumor diagnosed in
      children under the age of 14 years. Chronic health conditions related to
      endocrine and metabolic late effects are one of the most common medical late
      effects seen in childhood cancer survivors. Over the past 2 decades, outcomes
      have improved significantly for children diagnosed with a brain tumor. Curative
      therapy for childhood brain tumors survivors places them at significant risk for
      complex multi-organ medical late effects.These late effects can create a negative
      effect on cognition, growth, organ function, body image, sexual function and
      quality of life. Treatment related complications can occur many years after
      completion of therapy. Close monitoring is necessary so that early detection and
      intervention can hopefully decrease the full negative impact of many of these
      effects. Lifelong medical surveillance with a multidisciplinary team approach is
      essential to maximize health and improve the quality of life of survivors of
      pediatric brain tumors.

PMID- 19837960
TI  - Exploring family management of childhood brain tumor survivors.
AB  - Family management of childhood chronic conditions consists of 6 family factors:
      (1) the family's view of the child's daily life, (2) the impact of the condition
      on family life, (3) the difficulty of family life, (4) the family's effort
      managing the child's condition, (5) the family's ability managing the child's
      condition, and (6) parental mutuality. Recently, the Family Management Measure
      (FaMM), which measures family management of children with chronic conditions
      (excluding cancer), was validated. The purpose of this descriptive study was to
      examine the comparability of these 6 factors in families with childhood brain
      tumor survivors. First, 14 advanced practice nurses who are experts in neuro
      oncology and survivorship rated items on the FaMM as relevant and clear to
      families of brain tumor survivors. Second, 22 cognitive interviews with parents
      of brain tumor survivors described family management as comparable with families
      of children with other chronic illness. In this report, 2 hypothetical,
      contrasting case studies of family management are used to illustrate family
      management within the context of brain tumor survivors.

PMID- 19837963
TI  - The National Social Life, Health, and Aging Project: an introduction.

PMID- 19837969
TI  - Sodium ferulate modified gene expression profile of oxidized low-density
      lipoprotein-stimulated human umbilical vein endothelial cells.
AB  - Oxidized low-density lipoprotein (ox-LDL) is known to trigger vascular injury in
      atherosclerosis development. Sodium ferulate is an effective component from
      Chinese medicines with various beneficial cardiovascular pharmacological
      activities. Here, we investigated the effects of sodium ferulate on the gene
      expression profile of ox-LDL-stimulated endothelial cells. Cultured human
      umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (50 microg/mL)
      in the absence or presence of sodium ferulate (5 micromol/L). Sodium ferulate
      significantly reduced ox-LDL-induced endothelial cell death as evaluated by cell
      viability assay. Human oligonucleotide microarray analysis demonstrated that a
      total of 32 ox-LDL-induced genes were significantly downregulated to control
      levels by sodium ferulate. These genes included members from families of
      chemokine, inflammatory factor, growth factor, and nuclear receptor. These data
      provided an overview of the gene expression profile of endothelial cells in
      response to ox-LDL and sodium ferulate, and demonstrated that sodium ferulate
      could regulate the expression of inflammation-related genes in endothelial cells
      and has the potential to benefit endothelial function in the setting of
      atherosclerosis.

PMID- 19837970
TI  - Hospice disease types which indicate a greater need for bereavement counseling.
AB  - This article attempts to find a correlation between certain disease types and
      increased needs for bereavement services for survivors. Data were examined from
      those requesting increased bereavement services from a hospice provider in
      Kentucky, over a 2-year span. The survivors were then matched with the disease
      type of their loved one to see whether there was a connection between the two.
      Although limited in its scope and focus, the study revealed that patients
      surviving Alzheimer disease, lung cancer, and renal failure consistently (at
      least 50% of the time) required increased bereavement services after the death of
      their loved one. Other disease types indicated more erratic patterns for
      increased grief services.

PMID- 19837971
TI  - Family support services in pediatric palliative care.
AB  - A fundamental premise of pediatric palliative care is that support is provided
      not only to the ill child but to the family as well. In doing so, a number of
      services may be offered to family members throughout the child's illness, at the
      time of death and into bereavement, such as respite, counseling, expressive
      therapies, and bereavement support. Support may also be needed for the child's
      peers at school, church, or on sporting teams. Evidence on family supportive care
      in pediatric palliative care research is scarce. The majority of existing studies
      are undertaken with bereaved parents. Although these studies are insightful,
      further information is needed to understand families' needs along the illness
      trajectory and to determine whether unmet needs exist.

PMID- 19837972
TI  - Pathways to poly-victimization.
AB  - Some children, whom we have labeled poly-victims, experience very high levels of
      victimizations of different types. This article finds support for a conceptual
      model suggesting that there may be four distinct pathways to becoming such a poly
      victim: (a) residing in a dangerous community, (b) living in a dangerous family,
      (c) having a chaotic, multiproblem family environment, or (d) having emotional
      problems that increase risk behavior, engender antagonism, and compromise the
      capacity to protect oneself. It uses three waves of the Developmental
      Victimization Survey, a nationally representative sample of children aged 2-17
      years. All four hypothesized pathways showed significant independent association
      with poly-victim onset. For the younger children, the symptom score representing
      emotional problems was the only significant predictor. For the older children,
      the other three pathway variables were significant predictors--dangerous
      communities, dangerous families, and problem families--but not symptom score.
      Poly-victimization onset was also disproportionately likely to occur in the year
      prior to children's 7th and 15th birthday, corresponding roughly to the entry
      into elementary school and high school. The identification of such pathways and
      the ages of high onset should help practitioners design programs for preventing
      vulnerable children from becoming poly-victims.

PMID- 19837975
TI  - A gene expression signature of CD34+ cells to predict major cytogenetic response
      in chronic-phase chronic myeloid leukemia patients treated with imatinib.
AB  - In chronic-phase chronic myeloid leukemia (CML) patients, the lack of a major
      cytogenetic response (< 36% Ph(+) metaphases) to imatinib within 12 months
      indicates failure and mandates a change of therapy. To identify biomarkers
      predictive of imatinib failure, we performed gene expression array profiling of
      CD34(+) cells from 2 independent cohorts of imatinib-naive chronic-phase CML
      patients. The learning set consisted of retrospectively selected patients with a
      complete cytogenetic response or more than 65% Ph(+) metaphases within 12 months
      of imatinib therapy. Based on analysis of variance P less than .1 and fold
      difference 1.5 or more, we identified 885 probe sets with differential expression
      between responders and nonresponders, from which we extracted a 75-probe set
      minimal signature (classifier) that separated the 2 groups. On application to a
      prospectively accrued validation set, the classifier correctly predicted 88% of
      responders and 83% of nonresponders. Bioinformatics analysis and comparison with
      published studies revealed overlap of classifier genes with CML progression
      signatures and implicated beta-catenin in their regulation, suggesting that
      chronic-phase CML patients destined to fail imatinib have more advanced disease
      than evident by morphologic criteria. Our classifier may allow directing more
      aggressive therapy upfront to the patients most likely to benefit while sparing
      good-risk patients from unnecessary toxicity.

PMID- 19837976
TI  - EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2alpha-mediated
      regulation of soluble VEGF isoforms and their receptor VEGFR-2.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) is thought to
      promote tumor angiogenesis mostly through its protease-inducing function and more
      recently by its ability to increase tumor cell expression of vascular endothelial
      growth factor (VEGF). In this study, we present evidence that EMMPRIN can promote
      angiogenesis by a direct effect on endothelial cells through a paracrine
      regulation of the VEGF/VEGF-receptor (VEGFR) system. Using human microvascular
      endothelial cell line-1 endothelial cells, we show that EMMPRIN selectively
      increased the soluble VEGF isoforms (121 and 165), but not the matrix-bound VEGF
      189 form. In addition, EMMPRIN up-regulated the expression of VEGFR-2 without an
      effect on VEGFR-1. This increase in VEGFR-2 was responsible for the observed
      EMMPRIN stimulation of the migratory and tube formation capacity of endothelial
      cells. EMMPRIN's effects, which were matrix metalloproteinase and urokinase-type
      plasminogen activator independent, were mediated primarily through hypoxia
      inducible factor-2alpha expression, also up-regulated by EMMPRIN. VEGFR-2
      increase was also observed in vivo in a mouse model of xenograph tumors
      overexpressing EMMPRIN. These results suggest that in addition to increasing
      protease production, EMMPRIN may contribute to the formation of a reactive stroma
      also through the up-regulation of hypoxia-inducible factor-2alpha, VEGFR-2, and
      the soluble forms of VEGF in endothelial cells, thus directly regulating the
      angiogenic process.

PMID- 19837977
TI  - Migrating monocytes recruited to the spleen play an important role in control of
      blood stage malaria.
AB  - Host responses controlling blood-stage malaria include both innate and acquired
      immune effector mechanisms. During Plasmodium chabaudi infection in mice, a
      population of CD11b(high)Ly6C(+) monocytes are generated in bone marrow, most of
      which depend on the chemokine receptor CCR2 for migration from bone marrow to the
      spleen. In the absence of this receptor mice harbor higher parasitemias. Most
      importantly, splenic CD11b(high)Ly6C(+) cells from P chabaudi-infected wild-type
      mice significantly reduce acute-stage parasitemia in CCR2(-/-) mice. The
      CD11b(high)Ly6C(+) cells in this malaria infection display effector functions
      such as production of inducible nitric oxide synthase and reactive oxygen
      intermediates, and phagocytose P chabaudi parasites in vitro, and in a proportion
      of the cells, in vivo in the spleen, suggesting possible mechanisms of parasite
      killing. In contrast to monocyte-derived dendritic cells, CD11b(high)Ly6C(+)
      cells isolated from malaria-infected mice express low levels of major
      histocompatibility complex II and have limited ability to present the P chabaudi
      antigen, merozoite surface protein-1, to specific T-cell receptor transgenic CD4
      T cells and fail to activate these T cells. We propose that these monocytes,
      which are rapidly produced in the bone marrow as part of the early defense
      mechanism against invading pathogens, are important for controlling blood-stage
      malaria parasites.

PMID- 19837978
TI  - How I treat age-related morbidities in elderly persons with hemophilia.
AB  - In persons with hemophilia, life expectancy is now approaching that of the
      general male population, at least in countries that can afford regular
      replacement therapy with coagulation factor concentrates. The new challenges for
      comprehensive treatment centers are thus to provide optimal health care for this
      aging population of patients, who often present not only with the comorbidities
      typically associated with hemophilia (arthropathy, chronic pain, blood-borne
      infections), but also with common age-related illnesses such as cardiovascular
      disease and cancer. There are no evidence-based guidelines for the management of
      these conditions, which often require drugs that interfere with hemostasis,
      enhance the bleeding tendency, and warrant more intensive replacement therapy. At
      the moment, elderly patients with hemophilia affected by other diseases should be
      managed like their age-group peers without hemophilia, provided replacement
      therapy is tailored to the heightened risk of bleeding associated with the need
      for invasive procedures and drugs that further compromise the deranged
      hemostasis. More detailed advice is provided on the schedules of replacement
      therapy needed to tackle cardiovascular diseases, such as acute coronary
      syndromes and nonvalvular atrial fibrillation, because these conditions will
      become more and more frequent challenges for the comprehensive treatment centers.

PMID- 19837979
TI  - Identification of early growth response protein 1 (EGR-1) as a novel target for
      JUN-induced apoptosis in multiple myeloma.
AB  - Tumor-bone marrow microenvironment interactions in multiple myeloma (MM) are
      documented to play crucial roles in plasma-cell growth/survival. In vitro
      coculture of MM cells with osteoclasts supported cell survival and significantly
      down-regulated JUN expression. JUN expression in myeloma cells from late-stage
      and high-risk MM was significantly lower than in plasma cells from healthy
      donors, monoclonal gammopathy of undetermined significance, smoldering MM, and
      low-risk MM; patients with low-JUN-expressing MM cells had earlier disease
      related deaths. JUN overexpression in MM cells induced cell death and growth
      inhibition and up-regulated expression of early growth response protein 1 (EGR
      1), whose low expression also carried unfavorable clinical implications. EGR-1
      knockdown in MM cells abrogated JUN overexpression-induced MM cell death and
      growth inhibition, indicating that EGR-1 acts directly downstream of JUN. JUN
      modulates myeloma cell apoptosis through interacting with EGR-1, which down
      regulates Survivin and triggers caspase signaling. Importantly, high JUN or EGR-1
      expression was associated with improved outcome in Total Therapy 3, in which
      bortezomib is given throughout therapy, versus Total Therapy 2, in which
      bortezomib is given only at relapse. Consistently, JUN or EGR-1 knockdown in
      cultured MM cells enhanced their resistance to bortezomib, demonstrating the
      crucial role of low JUN/EGR-1 expression in MM resistance to bortezomib.

PMID- 19837980
TI  - Frameshift deletion by Sulfolobus solfataricus P2 DNA polymerase Dpo4 T239W is
      selective for purines and involves normal conformational change followed by slow
      phosphodiester bond formation.
AB  - The human DNA polymerase kappa homolog Sulfolobus solfataricus DNA polymerase IV
      (Dpo4) produces "-1" frameshift deletions while copying unmodified DNA and, more
      frequently, when bypassing DNA adducts. As judged by steady-state kinetics and
      mass spectrometry, bypass of purine template bases to produce these deletions
      occurred rarely but with 10-fold higher frequency than with pyrimidines. The DNA
      adduct 1,N(2)-etheno-2'-deoxyguanosine, with a larger stacking surface than
      canonical purines, showed the highest frequency of formation of -1 frameshift
      deletions. Dpo4 T239W, a mutant we had previously shown to produce fluorescence
      changes attributed to conformational change following dNTP binding opposite
      cognate bases (Beckman, J. W., Wang, Q., and Guengerich, F. P. (2008) J. Biol.
      Chem. 283, 36711-36723), reported similar conformational changes when the
      incoming dNTP complemented the base following a templating purine base or bulky
      adduct (i.e. the "+1" base). However, in all mispairing cases, phosphodiester
      bond formation was inefficient. The frequency of -1 frameshift events and the
      associated conformational changes were not dependent on the context of the
      remainder of the sequence. Collectively, our results support a mechanism for -1
      frameshift deletions by Dpo4 that involves formation of active complexes via a
      favorable conformational change that skips the templating base, without causing
      slippage or flipping out of the base, to incorporate a complementary residue
      opposite the +1 base, in a mechanism previously termed "dNTP-stabilized
      incorporation." The driving force is attributed to be the stacking potential
      between the templating base and the incoming dNTP base.

PMID- 19837981
TI  - Performance metrics for liquid chromatography-tandem mass spectrometry systems in
      proteomics analyses.
AB  - A major unmet need in LC-MS/MS-based proteomics analyses is a set of tools for
      quantitative assessment of system performance and evaluation of technical
      variability. Here we describe 46 system performance metrics for monitoring
      chromatographic performance, electrospray source stability, MS1 and MS2 signals,
      dynamic sampling of ions for MS/MS, and peptide identification. Applied to data
      sets from replicate LC-MS/MS analyses, these metrics displayed consistent,
      reasonable responses to controlled perturbations. The metrics typically displayed
      variations less than 10% and thus can reveal even subtle differences in
      performance of system components. Analyses of data from interlaboratory studies
      conducted under a common standard operating procedure identified outlier data and
      provided clues to specific causes. Moreover, interlaboratory variation reflected
      by the metrics indicates which system components vary the most between
      laboratories. Application of these metrics enables rational, quantitative quality
      assessment for proteomics and other LC-MS/MS analytical applications.

PMID- 19837983
TI  - Assisted reproductive techniques and human reproduction.

PMID- 19837982
TI  - Proteomics analysis of A33 immunoaffinity-purified exosomes released from the
      human colon tumor cell line LIM1215 reveals a tissue-specific protein signature.
AB  - Exosomes are 40-100-nm-diameter nanovesicles of endocytic origin that are
      released from diverse cell types. To better understand the biological role of
      exosomes and to avoid confounding data arising from proteinaceous contaminants,
      it is important to work with highly purified material. Here, we describe an
      immunoaffinity capture method using the colon epithelial cell-specific A33
      antibody to purify colorectal cancer cell (LIM1215)-derived exosomes. LC-MS/MS
      revealed 394 unique exosomal proteins of which 112 proteins (28%) contained
      signal peptides and a significant enrichment of proteins containing coiled coil,
      RAS, and MIRO domains. A comparative protein profiling analysis of LIM1215-,
      murine mast cell-, and human urine-derived exosomes revealed a subset of proteins
      common to all exosomes such as endosomal sorting complex required for transport
      (ESCRT) proteins, tetraspanins, signaling, trafficking, and cytoskeletal
      proteins. A conspicuous finding of this comparative analysis was the presence of
      host cell-specific (LIM1215 exosome) proteins such as A33, cadherin-17,
      carcinoembryonic antigen, epithelial cell surface antigen (EpCAM), proliferating
      cell nuclear antigen, epidermal growth factor receptor, mucin 13, misshapen-like
      kinase 1, keratin 18, mitogen-activated protein kinase 4, claudins (1, 3, and 7),
      centrosomal protein 55 kDa, and ephrin-B1 and -B2. Furthermore, we report the
      presence of the enzyme phospholipid scramblase implicated in transbilayer lipid
      distribution membrane remodeling. The LIM1215-specific exosomal proteins
      identified in this study may provide insights into colon cancer biology and
      potential diagnostic biomarkers.

PMID- 19837985
TI  - [MT1 melatonin receptors and their role in the oncostatic action of melatonin].
AB  - Melatonin, the main hormone produced by the pineal gland, strongly inhibits the
      growth of cancer cells in vitro and in vivo. Some publications indicate that the
      addition of melatonin to culture medium slows the proliferation of some cancer
      cell lines. It is also suggested that melatonin used as an adjuvant benefits the
      effectiveness and tolerance of chemotherapy. The mechanisms of this are not fully
      understood, but melatonin receptors might be one of the most important elements.
      Two distinct types of membrane-bound melatonin receptors have been identified in
      humans: MT1 (Mel1a) and MT2 (Mel1b) receptors. These subtypes are 60% homologous
      at the amino-acid level. MT1 receptors are G-protein-coupled receptors. Through
      the a subunit of G protein, melatonin receptors stimulate an adenylate cyclase
      and decrease the level of cAMP. This has a significant influence on cell
      proliferation and has been confirmed in many tests on different cell lines, such
      as S-19, B-16 murine melanoma cells, and breast cancer cells. It seems that
      expression of the MT1 melatonin receptors benefits the efficacy of melatonin
      treatment. Melatonin and its receptors may provide a promising way to establish
      new alternative therapeutic approaches in human cancer prevention.

PMID- 19837984
TI  - Structural basis of the interaction between chemokine stromal cell-derived factor
      1/CXCL12 and its G-protein-coupled receptor CXCR4.
AB  - The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its G-protein
      coupled receptor (GPCR) CXCR4 play fundamental roles in many physiological
      processes, and CXCR4 is a drug target for various diseases such as cancer
      metastasis and human immunodeficiency virus, type 1, infection. However, almost
      no structural information about the SDF-1-CXCR4 interaction is available, mainly
      because of the difficulties in expression, purification, and crystallization of
      CXCR4. In this study, an extensive investigation of the preparation of CXCR4 and
      optimization of the experimental conditions enables NMR analyses of the
      interaction between the full-length CXCR4 and SDF-1. We demonstrated that the
      binding of an extended surface on the SDF-1 beta-sheet, 50-s loop, and N-loop to
      the CXCR4 extracellular region and that of the SDF-1 N terminus to the CXCR4
      transmembrane region, which is critical for G-protein signaling, take place
      independently by methyl-utilizing transferred cross-saturation experiments along
      with the usage of the CXCR4-selective antagonist AMD3100. Furthermore, based upon
      the data, we conclude that the highly dynamic SDF-1 N terminus in the 1st step
      bound state plays a crucial role in efficiently searching the deeply buried
      binding pocket in the CXCR4 transmembrane region by the "fly-casting" mechanism.
      This is the first structural analyses of the interaction between a full-length
      GPCR and its chemokine, and our methodology would be applicable to other GPCR
      ligand systems, for which the structural studies are still challenging.

PMID- 19837986
TI  - [Diagnostic value of specific anty-HLA alloantibodies before and after renal
      transplantation. Programs for highly sensitized recipients].
AB  - Anti-HLA alloantibodies are the main barrier in kidney transplantation. Lack of
      appropriate donors for highly sensitized (HS) recipients makes access to
      transplantation very difficult and results in a significant increase in both the
      time on the waiting list and the number of post-transplant complications in these
      patients. The transplantation itself is also associated with higher risk in the
      HS. There are many programs aimed at increasing access to renal transplantation
      for this group of recipients. It is noteworthy that new acceptable HLA-mismatches
      allowed significant progress in programs for HS recipients. Currently implemented
      programs (ET-AMP, UNOS, Emory algorithm) proved useful as they increased access
      to transplantation and graft survival in HS patients. Nevertheless, even with
      these programs there is still the problem of humoral rejection in these patients.
      The strong correlation between donor-specific antibodies (DSA) and graft
      rejection seen both immediately after transplantation and in long-term
      complications such as CAN (chronic allograft nephropathy) may be the simplest
      explanation for this effect. Hence the assessment of alloantibodies limited to
      the pre-transplant period, which is nowadays routine, seems insufficient. Current
      evidence suggests that early detection of post-transplant DSA may be an excellent
      prognostic marker of graft function and may allow implementing the necessary
      treatment prior to rejection.

PMID- 19837987
TI  - [Biology of epidermal stem cells: impact on medicine].
AB  - The epidermis is a self-renewing tissue which regenerates constantly. It consists
      mainly of keratinocytes of various degree of differentiation, from the
      proliferative basal layer to the terminally differentiated horny layer.
      Keratinocytes are specialized cells responsible for cohesion, barrier functions,
      and immunological reactions. The maintenance of homeostasis in the epidermis is
      possible via the self-renewing ability of the epidermal stem-cell population,
      which gives rise to differentiated keratinocytes. It is believed that epidermal
      stem cells play an important role in cellular regeneration, wound healing, and
      the pathogenesis of skin cancers. Epidermal stem cells reside in the basal layer
      of the epidermis, the bulge region of the hair follicle, and the germinal hair
      follicle matrix. Epidermal stem cells are relatively quiescent, slow-cycling
      cells defined by their great proliferative potential and unlimited capacity for
      self-renewal. Adult human epidermal stem cells can be activated and expanded in
      vitro under appropriate conditions. Cultured human keratinocytes and epidermal
      stem cells may be then transplanted as a biological dressing in burn injuries,
      chronic wounds, and various skin diseases. Additionally, epidermal stem cells
      have become a target for gene therapy and drug testing. In this review the
      fundamental characteristics of epidermal stem cells and the signaling pathways
      involved in the regulation of their proliferation and differentiation are
      discussed. The possibilities of using epidermal stem cells in medicine are also
      presented.

PMID- 19837988
TI  - [The impact of sodium citrate on dialysis catheter function and frequency of
      catheter-related bacteriemia and haemorrhage].
AB  - Vascular access is one of the most important problems of hemodialysis therapy. It
      is known that an arteriovenous fisutla provides the best vascular access, but its
      creation is not always possible. Other solutions, such as the insertion of a
      central venous catheter, are then required. Adequate protection of such catheters
      by interdialytic fill with locking solution affects the frequency of hemodialysis
      related complications. The most widespread catheter locking solution is heparin.
      Sodium citrate is being used more frequent recently. Available data indicate that
      hemorrhage is 11.9 times more frequent if the catheter locking solution is 5000
      IU/ml heparin than if 4% sodium citrate or 1000 IU/ml heparin is used. Other data
      indicate that the frequency of infection is statistically decreased when 30%
      sodium citrate is used to fill the catheter instead of 5000 IU/ml heparin.
      Analogous data on 46.7% sodium citrate are not consistent. It seems that the use
      of 4% sodium citrate instead of 5000 IU/ml heparin does not decrease the
      frequency of infections. Numerous studies indicate that sodium citrate at various
      concentrations exerts a positive influence on catheter function. However, not all
      data are in accord. The spill of sodium citrate from the catheter to the systemic
      circulation is connected with a risk of adverse events. It may be dangerous if
      the citrate concentration is 46.7%. However, adequate filling of the catheter
      should prevent such events. Available data indicate that filling of the catheter
      with a solution of citrate of a concentration of no more than 30% should be safe.
      Data on 46.7% citrate are not conclusive, so precautions should be taken.

PMID- 19837989
TI  - [Balanced chromosomal rearrangements resulting in intellectual disability. An
      analysis of 22 cases with application of CGH and FISH methods].
AB  - INTRODUCTION: In approximately 6% of balanced chromosomal rearrangements
      carriers, intellectual disability, dysmorphic features and congenital anomalies
      can be found. The abnormal phenotype might be the result of genomic imbalance or
      aberrant expression caused by direct breakage of a dosage sensitive gene. THE AIM
      OF THIS STUDY: To estimate the frequency and implication of the submicroscopic
      chromosomal aberrations on the abnormal phenotypes present in patients with
      balanced chromosomal rearrangements. Also an attempt was made to define the type
      of genetic defect and gene identification responsible for the intellectual
      disability and additional clinical features. MATERIAL AND METHODS: 22 patients
      with intellectual disability, congenital anomalies and dysmorphic features were
      analysed. Molecular karyotyping was performed in all patients using FISH with
      region-specific BAC clones, high resolution comparative genomic hybridization (HR
      CGH) or array CGH (aCGH). A targeted or whole genome microarrays were applied.
      RESULTS: In 5 of 22 carriers 6 microdeletions and one duplication were found
      (7/22, 31.8%). Only two microdeletions were mapped at the chromosomal
      breakpoints. Three rearrangements had more complex structure than conventional
      methods demonstrated. In the chromosomal breakpoints of 21 patients the 24 genes,
      which functions suggest the relationship between abnormal gene expression and
      patients' intellectual disability, were mapped. CONCLUSIONS: We showed that in a
      considerable group of patients with balanced chromosomal rearrangements and
      abnormal phenotype the cryptic aberrations, unidentified by conventional methods,
      are present. These results confirmed the legitimacy of detailed analysis of the
      chromosomal breakpoints as well as the whole genome screening with the use of new
      cytogenetic methods.

PMID- 19837990
TI  - [Gene mapping in 14 families with X-linked nonspecific mental retardation].
AB  - Mental retardation affects 2-3% of the population. The identification of
      nonspecific X-linked mental retardation genes represents a challenge of
      considerable medical and scientific importance. AIM: An attempt to identify new
      genes and mutations in known genes in 14 families with nonspecific X-linked
      mental retardation. MATERIAL AND METHODS: Linkage analysis with microsatellite
      markers was performed in 14 families with mental retardation segregating as an X
      linked feature. Significant lod score (> 2) was obtained only for 2 families, due
      to insufficient number of analyzed families' members. Known MRX genes located in
      the linkage intervals were analysed. RESULTS: Analysis of selected known MRX
      genes enabled identification of pathogenic mutations in 3 out of 14 families.
      Sequencing of further candidate genes is in progress. In all families the
      critical region and the number of genes to analyze was significantly narrowed.
      CONCLUSIONS: Linkage analysis in families with mental retardation segregating as
      an X-linked feature is still a considerable approach leading to identification of
      new genes, and mutations in known genes. It is a first step of identification of
      disease background, even in small families with lod score < 2.

PMID- 19837991
TI  - [Analysis of genomic imprinting defects in Angelman syndrome with application of
      quantitative real-time PCR].
AB  - BACKGROUND: Angelman Syndrome (AS) is a neurogenetic disorder associated with
      aberrant genomic imprinting. AS patients with an imprinting defect have only
      paternal genes expression pattern despite the normal bi-parental inheritance of
      chromosome 15. In 2-3% of AS cases, the altered gene expression is a consequence
      of an imprinting defect (ID) such as microdeletions in imprinting centre (IC).
      Statistically, one third of patients with an imprinting defect and no IC deletion
      have somatic mosaicism. OBJECTIVES: The objectives of this study were:
      identification of somatic mosaicism for an imprinting defect in the patients with
      clinical manifestation of AS and development of a procedure for the
      identification of IC microdeletion. MATERIAL AND METHODS: Twenty eight AS
      patients with an aberrant methylation pattern confirmed in methylation screening
      procedure (MS-PCR) were qualified for mosaicism analysis with quantitative real
      time PCR technique. RESULTS: The quantitative analysis of methylated alleles did
      not confirm the presence of somatic mosaicism in any of the examined patients.
      CONCLUSIONS: The methods for somatic mosaicism and microdeletion in IC analyses
      based on quantitative real-time PCR technique can be used in the molecular
      diagnostic of Angelman syndrome.

PMID- 19837992
TI  - [Angelman syndrome--the research model of epigenetic mechanisms expression genes
      regulation].
AB  - Epigenetics, one of the widely investigated topics in human genetics, refers to
      phenotypic or gene expression changes caused by specific regulatory mechanisms
      (eg. DNA methylation, histone proteins modifications, antisense RNA or RNAi
      expression) that do not involve changes in DNA sequence. The disturbances in
      epigenetic gene expression regulatory mechanisms might lead to oncogenic
      transformation as well as monogenic or complex diseases. On the other side,
      better knowledge about epigenetic causes of certain diseases, gives an
      opportunity to potential therapies. One of the epigenetic research models in
      Angelman syndrome (AS). This neurologic disorder associated with improper central
      nervous system development and function, together with Prader-Willi syndrome are
      caused by the defects of epigenetic regulation. These disturbances are related to
      the defects of genomic imprinting, a phenomenon that contributes to allele
      specific, depending from parental origin, gene expression. In the majority of AS
      cases, the large deletion in chromosome 15 (15q11-13) of maternal origin (65-75%)
      or paternal disomy of chromosome 15 (3-7%) are observed. However, in a limited
      number of cases, other imprinting defects or mosaicism can be found and confirmed
      by new molecular biology techniques. Investigation of the etiology of the
      diseases caused by the defects in epigenetic regulation gives a basis to the
      development of epi-therapy that might be a promising alternative for their
      treatment. Moreover, knowledge about the epigenome gives an opportunity for
      prevention of human genetic disorders.

PMID- 19837993
TI  - [A case of hereditary over-hydrated stomatocytosis with stomatospherocytes and
      spherocytes in the blood].
AB  - A patient of 31 years of age with an atypical overhydrated hereditary
      stomatocytosis is described. The diagnosis was established on the basis of a
      markedly increased red cell volume with low MCHC, high osmotic fragility of red
      cells, but increased binding of eosin-5-maleimide (EMA) to red cells, presence of
      stomatospherocytes and large spherocytes in blood and a high sodium and low
      potassium concentration in erythrocytes. A double band 7 was found by SDS-PAGE of
      the erythrocyte membrane, but even when only one them was taken into account, the
      level of stomatin was normal. Expression of stomatospherocytes in patient's blood
      was erratic: in blood films prepared in 2005, both stomatospherocytes and large
      spherocytes were present but in those from 2008 large erythrocytes of spherocyte
      morphology predominated. Clinically, the disease symptoms were typical for
      haemolytic anemia. When heparinized blood of the patient was kept at 0 degrees
      Celsius for 24 h, the haemolysis of red cells amounted only to 2%. The patient's
      son, 5 years old, suffers from the same disease. CONCLUSION: In spite of its
      rarity, hereditary stomatocytosis and allied disorders should be taken into
      consideration in differential diagnosis of haemolytic anemia including newborns.
      The diagnosis is supported by finding increased binding of eosin-5-maleimide
      (EMA) dye to patients' erythrocytes associated with their elevated osmotic
      fragility. Absence of a significant count of stomatocytes in the blood does not
      exclude the diagnosis of overyhydrated hereditary stomatocytosis.

PMID- 19837994
TI  - [The C1155G mutation of the red blood cell glucose-6-phosphate dehydrogenase gene
      in a subject with severe hereditary chronic nonspherocytic anaemia].
AB  - THE AIM of the study is a genetic analysis of hereditary chronic nonspherocytic
      anaemia in a case, caused by mutation in the glucose-6-phosphate dehydrogenase
      gene. MATERIALS AND METHODS: The activity of G6PD enzyme was established. PCR
      method and DNA sequencing were implemented for molecular studies. Bioinformatic
      methods were used to check the effect of the mutation on the enzyme structure.
      RESULTS: Direct sequencing of g6pd gene revealed the presence of 1155 C > G
      mutation which results in cysteine to tryptophan substitution at position 385.
      Bioinformatic analysis established that this mutation may be responsible for
      protein destabilization. CONCLUSIONS: 1. G6PD deficiency should be considered in
      patients with haemolytic anaemia of unknown etiology. 2. Molecular tests are
      necessary, especially in cases of suspected mutation carriers in G6PD gene.

PMID- 19837995
TI  - [Detection of rare mutations in the dystrophin gene].
AB  - INTRODUCTION: Duchenne/Becker muscular dystrophies (DMD/BMD) are allelic X
      linked, recessive proximal muscle disorders, caused by mutations in the
      dystrophin gene located in Xp21. DMD occurs with the incidence 1:3500, BMD with
      the incidence of 1:18,500 new-born males. Approximately about 60% of mutations in
      the dystrophin gene are deletions, 10%--duplications and 30%--point mutations.
      AIM: The aim of the study was detection of the mutations: rare deletions,
      duplications and point mutations in the dystrophin gene in patients diagnosed as
      DMD/BMD in whom the presence of the most common deletions had previously been
      excluded. MATERIALS AND METHODS: Molecular analysis was performed using DNA
      samples isolated from 105 DMD and 10 BMD patients. Detection of rare deletions
      and duplications was carried out by Multiplex Ligation-dependent Probe
      Amplification (MLPA). Point mutations were identified by analysis of single
      strand conformation polymorphism (SSCP) and DNA sequencing. RESULTS: 38 Different
      mutations were detected: 10 rare deletions, 14 duplications and 14 point
      mutations and microdeletions. Majority of the detected rare deletions (7 out of
      10) and point mutations (11 out of 14) are novel mutations. CONCLUSIONS:
      Application of MLPA technique allows the detection of small, rare deletions and
      duplications. Identification of the nature and localization of the mutations may,
      in the future, help to apply appropriate therapeutic approaches in DMD patients.

PMID- 19837996
TI  - [Charcot-Marie-Tooth disorders with autosomal recessive inheritance. Search for
      the molecular diagnostics model].
AB  - THE AIM was focused on molecular analysis of the selected genes associated with
      autosomal recessive Charcot-Marie-Tooth neuropathies (AR-CMT) and construction of
      a molecular diagnostic algorithm in this group of disorders in the Polish
      population. MATERIAL AND METHODS: We analyzed a group of 138 subjects from 62
      families with probably autosomal recessive inheritance and the control group of
      52 individuals. The studies covered molecular genetic analysis of PMP22 gene
      dosage (real-time polymerase chain reaction and polymerase chain reaction
      restriction fragments length polymorphisms), analysis of coding regions of the
      GDAP1, PRX, EGR2 and CTDP1 genes using: mutation screening (single strand
      conformation polymorphism and heteroduplex analysis), sequencing and
      bioinformatics approach to the gene sequence variants. RESULTS: Thirty sequence
      variants have been found in the analysed genes, 5 pathogenic mutations in the
      GDAP1 gene and 2 pathogenic mutations in the PRX gene. On the basis of
      bioinformatic analysis other nucleotide changes have been categorized as harmless
      polymorphisms and variants of unknown pathogenic effect. CONCLUSIONS: This is the
      first study focused on the autosomal recessive Charcot-Marie-Tooth disease in the
      Polish population. Our results show the difficulties in the interpretation of the
      pathogenic effect of the sequence variants (pathogenic mutation or polymorphism)
      which is essential for molecular diagnostics in CMT disease.

PMID- 19837997
TI  - Fabrication of polycaprolactone collagen hydrogel constructs seeded with
      mesenchymal stem cells for bone regeneration.
AB  - The osteogenic differentiation of bone marrow-derived human mesenchymal stem
      cells (MSCs) in a collagen I hydrogel was investigated. Collagen hydrogels with
      7.5 x 10(5) MSCs ml(-1) were fabricated and cultured for 6 weeks in a defined,
      osteogenic differentiation medium. Histochemistry revealed morphologically
      distinct, chondrocyte-like cells, surrounded by a sulfated proteoglycan-rich
      extracellular matrix in the group treated with bone morphogenetic protein 2 (BMP
      2), while cells cultured with dexamethasone, ascorbate-2-phosphate, and beta
      glycerophosphate displayed a spindle-shaped morphology and deposited a
      mineralized matrix. Real-time polymerase chain reaction (RT-PCR) analyses
      revealed a specific chondrogenic differentiation with the expression of cartilage
      specific markers in the BMP-2-treated group and a distinct expression pattern of
      the osteogenic markers alkaline phosphatase (ALP), type I collagen, osteocalcin
      (OC), and cbfa-1 in the group treated with an osteogenic standard medium. The
      collagen gels were used to engineer a cell laden medical grade epsilon
      polycaprolactone (PCL)-hydrogel construct for segmental bone repair showing good
      bonding at the scaffold hydrogel interface and even cell distribution. The
      results show that MSCs cultured in a collagen I hydrogel are able to undergo a
      distinct osteogenic differentiation pathway when stimulated with specific
      differentiation factors and suggest that collagen I hydrogels are a suitable
      means to facilitate cell seeding of scaffolds for bone tissue engineering
      applications.

PMID- 19837998
TI  - External trial deep brain stimulation device for the application of
      desynchronizing stimulation techniques.
AB  - In the past decade deep brain stimulation (DBS)-the application of electrical
      stimulation to specific target structures via implanted depth electrodes-has
      become the standard treatment for medically refractory Parkinson's disease and
      essential tremor. These diseases are characterized by pathological synchronized
      neuronal activity in particular brain areas. We present an external trial DBS
      device capable of administering effectively desynchronizing stimulation
      techniques developed with methods from nonlinear dynamics and statistical physics
      according to a model-based approach. These techniques exploit either stochastic
      phase resetting principles or complex delayed-feedback mechanisms. We explain how
      these methods are implemented into a safe and user-friendly device.

PMID- 19837999
TI  - Design and characteristics of holographic neural photo-stimulation systems.
AB  - Computer-generated holography is an emerging technology for stimulation of
      neuronal populations with light patterns. A holographic photo-stimulation system
      may be designed as a powerful research tool or a compact neural interface medical
      device, such as an optical retinal prosthesis. We present here an overview of the
      main design issues including the choice of holographic device, field-of-view,
      resolution, physical size, generation of two- and three-dimensional patterns and
      their diffraction efficiency, choice of algorithms and computational effort. The
      performance and characteristics of a holographic pattern stimulation system with
      kHz frame rates are demonstrated using experimental recordings from isolated
      retinas.

PMID- 19838000
TI  - Endomyocardial radial strain imaging and left ventricular relaxation
      abnormalities in patients with hypertrophic cardiomyopathy or hypertensive left
      ventricular hypertrophy.
AB  - BACKGROUND: Asymmetrical septal hypertrophy and impaired left ventricular (LV)
      diastolic function are common echocardiographic features of hypertrophic
      cardiomyopathy (HCM). However, it is difficult to differentiate nonobstructive
      HCM from hypertensive LV hypertrophy (H-LVH). METHODS AND RESULTS: Standard
      echocardiography and tissue Doppler imaging were performed in 14 patients with
      HCM, 16 patients with H-LVH, and 21 control subjects. Endomyocardial radial
      strain, systolic strain rate (SR), and the early diastolic SR at the posterior
      and septal segments of the LV short axis were calculated. Endomyocardial peak
      strain (epsilon) and the absolute value of peak early diastolic SR at the
      posterior segment were significantly smaller in patients with HCM than in those
      with H-LVH, whereas the thickness of the LV posterior wall did not differ between
      these 2 groups. Multivariate analysis of discrimination, including the ratio of
      interventricular septal thickness and posterior wall thickness (IVST/PWT),
      epsilon, and SR parameters, between HCM and H-LVH patients revealed that epsilon
      at the LV posterior segment was the highest discriminant parameter (discriminant
      coefficient: -14.6, P=0.012). The epsilon at the posterior segment significantly
      correlated with early diastolic mitral annular velocity. CONCLUSIONS:
      Endomyocardial radial strain imaging may prove informative for discriminating
      between HCM and H-LVH.

PMID- 19838001
TI  - Vascular integrity mediated by vascular endothelial cadherin and regulated by
      sphingosine 1-phosphate and angiopoietin-1.
AB  - Development of blood vessels is coordinated by angiogenesis and stabilization of
      vascular endothelial cells (ECs). The vascular network is established during
      embryogenesis to supply oxygen and nutrients to the tissues and organs. However,
      after cardiac or peripheral ischemia is caused by occlusion of the vessels, new
      vessels must be formed to rescue the ischemic tissues. Many angiogenic growth
      factors and chemokines are produced in the ischemic tissue to induce angiogenic
      sprouting of preexisting vessels. Branched vessels must be again restabilized to
      form mature vessels that deliver blood to the tissues. To this end, vascular EC
      cell adhesion is tightly regulated by cell-cell adhesion molecules and
      extracellular stimuli that activate G protein-coupled receptors and receptor
      tyrosine kinases exclusively expressed on vascular ECs. This review spotlights
      the recent studies of vascular endothelial cadherin and of sphingosine 1
      phosphate signaling and angiopoietin-Tie signaling.

PMID- 19838002
TI  - Dose-dependent prognostic effect of carvedilol in patients with chronic heart
      failure--special reference to transcardiac [corrected] gradient of
      norepinephrine.
AB  - BACKGROUND: The effect of the dose of carvedilol on cardiac sympathetic nerve
      activity (CSA) and mortality remain uncertain in patients with chronic heart
      failure (CHF). METHODS AND RESULTS: To compare the dose of carvedilol and the
      transcardiac gradient of norepinephrine (NE), a biomarker of CSA, and prognosis
      in patients with CHF, hemodynamic parameters and plasma levels of NE, N-terminal
      brain natriuretic peptide (NT-proBNP) in the aortic root and coronary sinus were
      measured in 107 patients with systolic CHF who received carvedilol. Patients were
      divided into 2 groups [group I: low dose (<10 mg/day, n=41) and group II: high
      dose (>or=10 mg/day, n=66)]. There was no difference between the 2 groups for the
      hemodynamic parameters. The dose of carvedilol did not correlate with plasma NE,
      but was significantly correlated with the transcardiac increase in NE. During a
      median follow-up of 4.3 years, 13 patients died of cardiac disease. In the Cox
      stepwise multivariate analyses, a high level of transcardiac increase in NE
      (P<0.001), high level of plasma log NT-proBNP (P=0.004) and low dose of
      carvedilol (P=0.012) were significant independent predictors. CONCLUSION: The
      carvedilol dose is important for the management of CSA and prognosis in patients
      with systolic CHF.

PMID- 19838003
TI  - Clinical profiles of hypertrophic cardiomyopathy with apical phenotype-
      comparison of pure-apical form and distal-dominant form.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) with an apical phenotype, in which
      hypertrophy of the myocardium predominantly involves the apex of the left
      ventricle, is not uncommon in Japan, but its morphologic variations are not well
      recognized. The aim of this study was to investigate if these variations have
      different clinical characteristics although they are still confused to be the
      same. METHODS AND RESULTS: Patients with the apical phenotype were divided into 2
      groups, the "pure-apical" form and the "distal-dominant" form, and their clinical
      profiles were compared. From the study cohort of 264 patients with HCM, 80 (30%)
      were classified as having the apical phenotype: 51 with the pure-apical form and
      29 with the distal-dominant form. The age at diagnosis was approximately 60
      years, and in both groups the majority were male. The distal-dominant group had a
      significantly larger left atrial diameter (43 vs 39 mm) and higher ratio of
      proven familial HCM (28 vs 6%), and were more symptomatic (New York Heart
      Association >or=3) at presentation (17 vs 0%). The event-free rate of
      cardiovascular events in patients with the distal-dominant form was significantly
      worse (log-rank P=0.012) than that in patients with the pure-apical form (follow
      up period: asymptotically approximately 5 years). CONCLUSIONS: The 2 phenotypes
      of apical HCM should be recognized and distinguished clinically.

PMID- 19838004
TI  - Ambulatory ECG-based T-wave alternans and heart rate turbulence predict high risk
      of arrhythmic events in patients with old myocardial infarction.
AB  - BACKGROUND: Few studies have explored risk stratification of arrhythmic events in
      patients with ischemic heart diseases according to T-wave alternans (TWA) using
      modified moving average (MMA) method and heart rate turbulence (HRT). METHODS AND
      RESULTS: A retrospective analysis of 63 patients who underwent MMA-based TWA and
      HRT divided the patients into 3 groups: group-C of 21 controls, group-O of 21
      patients with old myocardial infarction (OMI) showing no episodes of sustained
      ventricular tachyarrhythmia (SVT), and group-V of 21 OMI patients with episodes
      of SVT who received an implantable cardioverter-defibrillator. Among the 3
      groups, positive TWA (>or=65 microV) and impaired HRT were observed most
      frequently in group-V (P<0.05). Using a logistic regression model, TWA yielded an
      odds ratio of 4.9 (95% confidence interval: 1.2-19.6, P<0.05), which was the only
      significant covariate for the incidence of life-threatening ventricular
      arrhythmias during a mean follow-up of 72 months. CONCLUSIONS: Patients with OMI
      showing episodes of SVT have a high risk for cardiac death because of abnormal
      repolarization and autonomic regulation. The analysis of MMA-based TWA and HRT
      can be a useful tool for predicting OMI patients at high risk of arrhythmic
      events.

PMID- 19838005
TI  - Risk of smoking and metabolic syndrome for incidence of cardiovascular disease-
      comparison of relative contribution in urban Japanese population: the Suita
      study.
AB  - BACKGROUND: Risk factor clustering, the so-called metabolic syndrome (MetS), is
      an important risk factor for cardiovascular disease (CVD). Smoking is also an
      important CVD risk factor with still a high prevalence. However, few previous
      studies have compared the risk for CVD or the population-attributable fraction
      (PAF) of smoking, MetS, and both. METHODS AND RESULTS: The present study was an
      11.9-year cohort study of 1,822 men and 2,089 women, aged 40-74 years, selected
      randomly from an urban general population in Japan. MetS was defined according to
      the National Cholesterol Education Program on Adult Treatment Panel III (NCEP
      ATPIII) guideline modified by the Asian criteria for waist circumference. The
      prevalence of smoking was 49.5% in men and 11.1% in women, and that of MetS was
      19.8% and 23.5%, respectively. In men, the multivariate-adjusted hazard ratio for
      CVD incidence, compared with non-smoking participants without MetS, was 2.07
      (1.26-3.40) in those who smoked, 2.09 (1.08-4.04) in those with MetS, and 3.56
      (1.89-6.72) in those with both. In men the PAF for CVD incidence was 21.8%
      because of smoking, 7.5% because of MetS, and 11.9% because of both. CONCLUSIONS:
      Although countermeasures for MetS are important, smoking should continue to be
      considered an important public health problem and antismoking campaigns should be
      promoted, especially for men, to prevent CVD.

PMID- 19838006
TI  - Relationship between functional exercise capacity and functional stenosis in
      patients with stable angina and intermediate coronary stenosis.
AB  - BACKGROUND: Some stable angina patients with significant coronary function have
      low exercise capacity, whereas some have high exercise capacity. The aim of the
      present study was to determine whether coronary pressure-derived fractional flow
      reserve (FFRmyo), a functional index of coronary stenosis, is a better indicator
      of exercise capacity than angiographic stenosis. METHODS AND RESULTS: The 15 male
      (65.8 +/-8.9 years old) subjects with stable angina and 75% angiographic stenosis
      underwent a cardiopulmonary exercise test (CPX), and peak oxygen uptake
      (PeakVO(2)) and oxygen uptake at anaerobic threshold (AT) were measured. The
      relationship between FFRmyo and CPX values was assessed. The left anterior
      descending artery was affected in 8 patients, the left circumflex artery in 5,
      and the right coronary artery in 2. Percent diameter stenosis (%DS) was 61.7 +/
      9.1% by quantitative coronary angiography. Mean FFRmyo, PeakVO(2), and AT was
      0.84 +/-0.66, 17.1 +/-3.2 ml x kg(-1) x min(-1), and 11.1 +/-2.0 ml x kg(-1) x
      min(-1), respectively. There was no significant correlation between %DS and
      FFRmyo, PeakVO(2), or AT (r=0.12, 0.051, and 0.013, respectively; P=NS), but
      FFRmyo had a significant positive correlation with PeakVO(2) and AT (r=0.534 and
      0.542, respectively; P<0.05). CONCLUSIONS: Exercise capacity reflects functional
      stenosis in stable angina patients.

PMID- 19838008
TI  - A short history of tsunami research and countermeasures in Japan.
AB  - The tsunami science and engineering began in Japan, the country the most
      frequently hit by local and distant tsunamis. The gate to the tsunami science was
      opened in 1896 by a giant local tsunami of the highest run-up height of 38 m that
      claimed 22,000 lives. The crucial key was a tide record to conclude that this
      tsunami was generated by a "tsunami earthquake". In 1933, the same area was hit
      again by another giant tsunami. A total system of tsunami disaster mitigation
      including 10 "hard" and "soft" countermeasures was proposed. Relocation of
      dwelling houses to high ground was the major countermeasures. The tsunami
      forecasting began in 1941. In 1960, the Chilean Tsunami damaged the whole
      Japanese Pacific coast. The height of this tsunami was 5-6 m at most. The
      countermeasures were the construction of structures including the tsunami
      breakwater which was the first one in the world. Since the late 1970s, tsunami
      numerical simulation was developed in Japan and refined to become the UNESCO
      standard scheme that was transformed to 22 different countries. In 1983, photos
      and videos of a tsunami in the Japan Sea revealed many faces of tsunami such as
      soliton fission and edge bores. The 1993 tsunami devastated a town protected by
      seawalls 4.5 m high. This experience introduced again the idea of comprehensive
      countermeasures, consisted of defense structure, tsunami-resistant town
      development and evacuation based on warning.

PMID- 19838007
TI  - 4G/5G variant of plasminogen activator inhibitor-1 gene and severe pregnancy
      induced hypertension: subgroup analyses of variants of angiotensinogen and
      endothelial nitric oxide synthase.
AB  - BACKGROUND: Pregnancy-induced hypertension (PIH) is a common cause of perinatal
      mortality. It is believed to result from the interaction of several factors,
      including those related to the blood coagulation system. We performed genotyping
      and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen
      activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to
      evaluate possible interactions of the PAI-1 polymorphisms with those of the
      angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3).
      METHODS: An association study of PAI-1 polymorphism, and subgroup analyses of
      common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy
      pregnant controls. RESULTS: No significant differences were found between the
      cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In
      subgroup analyses, after adjustment for multiple comparison, a significant
      association with the AGT TT genotype was found among women with the PAI-1 4G/4G
      genotype, and an association with the NOS3 GA+AA genotype was found among women
      with the 5G/5G or 4G/5G genotypes. CONCLUSIONS: Our findings suggest that there
      are at least 2 pathways in the pathogenesis of severe PIH. However, with respect
      to early prediction and prevention of severe PIH, although the PAI-1 4G/4G
      genotype alone was not a risk factor for severe PIH, the fact that PAI-1
      genotypes are associated with varying risks for severe PIH suggests that PAI-1
      genotyping of pregnant women, in combination with other tests, may be useful in
      the development of individualized measures that may prevent severe PIH.

PMID- 19838009
TI  - Overview on the history of organofluorine chemistry from the viewpoint of
      material industry.
AB  - Fluorine (from "le fluor", meaning "to flow") is a second row element of Group 17
      in the periodic table. When bound to carbon it forms the strongest bond in
      organic chemistry to give organofluorine compounds. The scientific field treating
      them, organofluorine chemistry, started before elemental fluorine itself was
      isolated. Applying the fruits in academia, industrial organofluorine chemistry
      has developed over 80 years via dramatic changes during World War II. Nowadays,
      it provides various materials essential for our society. Recently, it utilizes
      elemental fluorine itself as a reagent for the introduction of fluorine atoms to
      organic molecules in leading-edge industries. This paper overviews the historical
      development of organofluorine chemistry especially from the viewpoint of material
      industry.

PMID- 19838010
TI  - Rational design of dynamic ammonium salt catalysts towards more flexible and
      selective function.
AB  - This review focuses on the development of dynamic ammonium salt catalysis for
      selective organic transformations conducted in our laboratory since 2002. Several
      important concepts in designing of catalysts are described with some examples. In
      particular, the practical synthesis of chiral 1,1'-binaphthyl-2,2'-disulfonic
      acid (BINSA) and its application in chiral ammonium salt catalysis for the
      enantioselective direct Mannich-type reaction are described.

PMID- 19838011
TI  - Transforming growth factor-beta signaling in epithelial-mesenchymal transition
      and progression of cancer.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that
      induces growth arrest, tissue fibrosis, and epithelial-mesenchymal transition
      (EMT) through activation of Smad and non-Smad signaling pathways. EMT is the
      differentiation switch by which polarized epithelial cells differentiate into
      contractile and motile mesenchymal cells. Cell motility and invasive capacity are
      activated upon EMT. Multiple transcription factors, including deltaEF1/ZEB1,
      SIP1/ZEB2, and Snail/SNAI1, are induced by TGF-beta-Smad signaling and play
      critical roles in TGF-beta-induced EMT. In addition, both non-Smad signaling
      activated by TGF-beta and cross-talk with other signaling pathways play important
      roles in induction of EMT. Of these, Ras signaling synergizes with TGF-beta-Smad
      signaling, and plays an important role in the induction of EMT. TGF-beta
      inhibitors prevent invasion and metastasis of advanced cancer through multiple
      mechanisms, including inhibition of EMT. The discovery of molecules that inhibit
      TGF-beta-induced EMT but not TGF-beta-induced growth arrest may be an ideal
      strategy for treatment of invasion and metastasis of cancer.

PMID- 19838012
TI  - Various facets of vertebrate cilia: motility, signaling, and role in adult
      neurogenesis.
AB  - Cilia are microtubule-based cellular organelles that are widely distributed in
      vertebrate tissues. They were first observed hundreds of years ago. Recent
      studies indicate that this small organelle plays important roles in numerous
      physiological phenomena, including tissue morphogenesis, signal transduction,
      determination of left-right asymmetry during development, and adult neurogenesis.
      Ciliopathies, syndromes resulting from a genetic disorder of cilial components,
      frequently have complex effects involving many organ systems, owing to the broad
      distribution of cilia in the body.

PMID- 19838013
TI  - Hermaphrodism and sex reversal associated with the dominant hemimelia mutation in
      XY mice.
AB  - After two generations of backcrossing six different Y-consomic strains onto a
      C57BL/6J inbred mouse strain with a dominant hemimelia (Dh) mutation, a small
      percentage of Dh/+ males containing a Y chromosome from the AKR/J or RF/J strain
      showed hermaphrodism; they lacked the right testis and had an ovary and a uterus
      instead. Approximately 15% of Dh/+ females considered to be phenotypically normal
      had the Sry gene from the AKR/J or RF/J strain; they were actually sex-reversed
      XY females. Backcrossing of Y chromosomes from BALB/cA, C3H/HeJ, C57BL/6J,
      DH/Sgn, and DDD/Sgn onto the C57BL/6J strain with Dh did not result in
      hermaphrodism or sex reversal in adult mice. Subsequent linkage mapping analysis
      revealed that at least one C57BL/6J-derived homozygous allele at a locus on
      chromosome 13 was required for hermaphrodism and sex reversal. This condition was
      genetically distinct from known inherited sex-reversal conditions. It therefore
      offers a novel opportunity to investigate the genetic basis of sex determination
      in mammals.

PMID- 19838015
TI  - [Cancer treatment and death studies].
AB  - In the West, death studies has become a new academic area since around 1970. The
      driving force is the hospice movement. People now ask questions such as how to
      care for dying people and their relatives. Because the main clients in hospice
      and palliative care are cancer patients, cancer treatment and death studies are
      closely linked to each other. The rise of death studies is connected with the
      awareness of the limits of modern medicine. Medical staffs are forced to learn
      how to care for those patients facing death. But modern medicine has put
      exclusive emphasis on biomedical treatment to cure. Contemporary medicine is
      becoming more and more aware of the psychological and spiritual needs of the
      patient. Today medicine and medical education have to incorporate the
      perspectives from death studies, learning how human beings facing death can live
      a better life not only in physical terms but also in psychological, social and
      spiritual terms.

PMID- 19838014
TI  - Efficient induction of transgene-free human pluripotent stem cells using a vector
      based on Sendai virus, an RNA virus that does not integrate into the host genome.
AB  - Induced pluripotent stem cells (iPSC) have been generated from somatic cells by
      introducing reprogramming factors. Integration of foreign genes into the host
      genome is a technical hurdle for the clinical application. Here, we show that
      Sendai virus (SeV), an RNA virus and carries no risk of altering host genome, is
      an efficient solution for generating safe iPSC. Sendai-viral human iPSC expressed
      pluripotency genes, showed demethylation characteristic of reprogrammed cells.
      SeV-derived transgenes were decreased during cell division. Moreover, viruses
      were able to be easily removed by antibody-mediated negative selection utilizing
      cell surface marker HN that is expressed on SeV-infected cells. Viral-free iPSC
      differentiated to mature cells of the three embryonic germ layers in vivo and in
      vitro including beating cardiomyocytes, neurons, bone and pancreatic cells. Our
      data demonstrated that highly-efficient, non-integrating SeV-based vector system
      provides a critical solution for reprogramming somatic cells and will accelerate
      the clinical application.

PMID- 19838016
TI  - [Changes in the concept of neuroendocrine tumor].
AB  - Neuroendocrine tumor is defined as the tumor associated with neuroendocrine
      differentiation. There have been confusions regarding the concept of
      neuroendocrine tumor. This has been especially complicated by the long-standing
      concept of Karzinoide Tumor proposed by Oberndofer. Neuroendocrine
      differentiation has been examined by histochemical methods such as Grimelius
      method or identification of neurosecretory granules but is in general
      characterized by immunohistochemistry of neuroendocrine markers such as
      chromogranine A. In addition, neuroendocrine tumor is currently classified into:
      1. Welldifferentiated endocrine tumor; 2. Well-differentiated endocrine
      carcinoma; 3. Poorly-differentiated endocrine(small cell) carcinoma; 4. Mixed
      exocrine-endocrine tumor; and 5. Tumor-like lesion according to its degree of
      differentiation, cell proliferation or other histological features. Especially,
      cell proliferation determined by Ki67/MIB1 labeling index plays important roles
      in this classification. This new classification is important not only in
      predicting the prognosis of patients with neuroendocrine tumor but also in
      defining the modes of treatment, and it has become important for those involved
      in clinical management of these patients to be familiar with this classification.

PMID- 19838017
TI  - [Treatment of neuroendocrine tumors of the digestive tract].
AB  - Neuroendocrine tumors of the digestive tract are relatively rare and comprise
      benign and malignant tumors. WHO classification system is based on recognized
      differences in morphology, function and clinical behavior. European
      Neuroendocrine Tumor Society(ENETS)proposed grading system and TNM classification
      system with disease staging for endocrine tumors of each organ which are both
      valid tools for prognostic stratification. The only curative therapy is the
      complete resection of the tumor. Endoscopic submucosal dissection(ESD)or local
      resection can be performed in low grade and early stage tumors; on the other
      hand, curative resection with lymph node dissection is recommended for
      neuroendocrine carcinoma. Complete surgical resection of liver metastases is
      associated with better long-term survival. Combination chemotherapy, such as
      Etoposide+Cisplatin/Carboplatin, is useful in treating unresected neuroendocrine
      carcinomas. Octreotide and Pasireotide (SOM230), somatostatin analogues, are
      reported to have the benefit of both hormonal symptom control and tumor growth
      suppression. Development of new effective drug is expected for the treatment of
      neuroendocrine tumors of the digestive tract.

PMID- 19838018
TI  - [Diagnosis and treatment of pancreatic endocrine tumors].
AB  - The incidence of pancreatic endocrine tumor (PET)accounts for 1 approximately 2%
      of total pancreatic tumors and 0. 4 approximately 1. 5% of autopsy cases,
      reflecting the recently increasing trend. According to WHO criteria(2004), PET is
      classified by the type of hormone produced by the tumor and its biological
      behavior. Together with the classical clinical images and hormone markers, 11C-5
      HTP-Positron emission tomography, OctreoScan ([(111)In
      DTPA0]octreotide)scintigram, SACI-test and IOUS are used for diagnosis. Surgery
      is the treatment of choice, if supposed to be curative and tolerable. In case of
      a well-differentiated endocrine tumor, with no indication of resection or IVR,
      somatostatin analog is another therapy showing stable disease status for a long
      period. Systemic chemotherapy, including 5-FU+streptozotocin, and
      streptozotocin+doxorubicin, are used in cases of well -differentiated endocrine
      carcinoma, and cisplatin+etoposide are applied for poorly-differentiated
      endocrine carcinoma (or small cell carcinoma). Recent studies focus on molecular
      target therapy including small molecules and monoclonal antibody, such as
      tyrosine kinase inhibitor, anti-VEGF antibody and moor inhibitor.

PMID- 19838019
TI  - [Treatment strategy for neuroendocrine carcinoma of the lung].
AB  - Neuroendocrine carcinoma of the lung is classified into typical carcinoid (TC),
      atypical carcinoid (ATC), large cell neuroendocrine carcinoma (LCNEC) and small
      cell carcinoma (SCLC). The standard treatment of carcinoid tumor is surgical
      resection. There is no standard therapy for LCNEC. Generally, the treatment of
      LCNEC is surgical resection and postoperative adjuvant chemotherapy in stage I
      and II, concurrent chemo-radiotherapy in stage III, and combination chemotherapy
      in stage IV. The treatment of SCLC is mainly combination chemotherapy. Standard
      therapy of SCLC is concurrent chemo-radiotherapy in limited disease and
      combination chemotherapy in extensive disease. Combination chemotherapy with
      cisplatin and etoposide is administered for limited disease, and cisplatin and
      irinotecan is administered for extensive disease. The surgical indication for
      SCLC is only stage I patients. Adjuvant chemotherapy is needed postoperatively.

PMID- 19838020
TI  - [Therapeutic strategy for pheochromocytoma].
AB  - Pheochromocytoma is the most common type of neuroendocrine tumor arising from the
      adrenal gland. Pheochromocytoma has been termed a 10% tumor because roughly 10%
      of such tumors are malignant, multifocal, bilateral, and arise in extra-adrenal
      sites. During the last decade, laparoscopic adrenalectomy has been the standard
      method to remove pheochromocytomas. Adrenal-sparing laparoscopic surgery is a
      treatment of choice for bilateral pheochromocytomas. Cyclophosphamide,
      vincristine and dacarbazine combined chemotherapy and (131)I-MIBG therapy are
      required for the treatment of metastatic or unresectable malignant
      pheochromocytoma.

PMID- 19838021
TI  - [The treatment of medullary thyroid cancer].
AB  - Medullary thyroid cancer( MTC) is a neuroendocrine tumor arising from neural
      crest-derived, calcitonin-secreting parafollicular C cells within the thyroid.
      Serum calcitonin (CT) is the most specific and sensitive marker for MTC for both
      the primary diagnosis and postsurgical follow-up. MTC may occur either
      sporadically or as part of a hereditary disease such as multiple endocrine
      neoplasia Type 2A (MEN 2A), multiple endocrine neoplasia Type 2B (MEN 2B) or
      familial medullary thyroid cancer(FMTC). The primary treatment of MTC is surgical
      removal of all neoplastic tissue present in the neck and lymph nodes; this should
      be performed after the careful exclusion of a phenochromocytoma. Mutations in the
      RET gene are associated with MEN2A, MEN2B and FMTC. Specific RET mutations are
      associated with each of the MEN2 syndromes and with the aggressiveness of MTC.
      Consequently, the nature of the RET mutation should guide major management
      decisions and inform the treatment strategy for MTC.

PMID- 19838022
TI  - [Clinical investigation of weekly Carboplatin and Paclitaxel with concurrent
      radiation therapy for locally advanced non-small cell lung cancer].
AB  - PURPOSE: The aim of this study was to evaluate retrospectively chemotherapy of
      weekly carboplatin and paclitaxel with concurrent radiation therapy for patients
      with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Between January 2000 and March 2008, 38 patients were treated by chemotherapy
      with carboplatin and paclitaxel once a week, repeated for 6 weeks, with thoracic
      radiation therapy of 1 or 2 times a day on weekdays. After concurrent
      chemoradiotherapy, we planned consolidation chemotherapy of carboplatin(AUC 5
      6)and weekly paclitaxel(70- 80 mg/m(2)) on day 1, 8 and 15, when possible.
      RESULTS: The enrolled patients were 31 men and 7 women, with the median age of 59
      years (39-76 years), stage III A/III B: 10/28, Ad/Sq/AdSq/Un: 17/17/2/2. The
      response rate of this chemoradiotherapy was 78. 9%. The median survival time and
      time to progression were 24. 7 months and 8. 1 months, respectively. Grade 3 or 4
      hematological toxicities during concomitant chemoradiotherapy were
      leukocytopenia(5. 2%)and neutropenia(5. 2%). Grade 3 or 4 non-hematological
      toxicities were esophagitis(2. 6%)and pneumonitis (5. 2%). There was a therapy
      associated death by radiation pneumonitis. CONCLUSION: Carboplatin and paclitaxel
      with concurrent radiation therapy for a patient with stage III NSCLC showed a
      good response with relatively mild side effects. We reached the conclusion that
      concurrent chemoradiotherapy would be a useful choice for locally advanced non
      small cell lung cancer on the practical clinic.

PMID- 19838023
TI  - [Gemcitabine in combination with S-1 or UFT in patients with advanced pancreatic
      cancer].
AB  - The present retrospective study aimed to evaluate the anti-tumor activity and
      toxicity of combination chemotherapy with gemcitabine (GEM) and oral S-1 or UFT
      in patients with advanced or metastatic pancreatic cancer. Ninety-four patients
      received chemotherapy. Among them, sixty-three were treated with GEM alone,
      twenty-two with UFT and GEM (UFT/GEM), and nine with S-1 and GEM(S-1/GEM). The
      median survival time was 8.7 months with GEM, 7.3 months with UFT/GEM, and 23.3
      months with S-1/GEM. The overall response rate was 11.1%, 10.0%, and 22.2%,
      respectively. The 1-year survival rate was 29.5%, 36.4%, and 85.7%, respectively.
      Although the treatment-related adverse effects were not infrequent in patients
      treated with S-1/GEM, they were moderate in intensity. The combination
      chemotherapy with S-1/GEM was well tolerated and yielded a high response rate in
      patients with pancreatic cancer.

PMID- 19838024
TI  - [Efficacy and safety of S-1 plus docetaxel combination therapy for patients with
      advanced gastric cancer].
AB  - Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP
      combination therapy has been reported. Docetaxel also has been reported to have
      favorable efficacy in gastric cancer. In addition, docetaxel can be administered
      in outpatient clinics. We investigated the efficacy and safety of S-1 plus
      docetaxel combination therapy for 35 naive patients with advanced gastric cancer.
      Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was
      administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by
      one week rest. MST was 300 days, and the response rate was 42. 9%. Although
      leucopenia was observed in 31%, all patients were able to be continue this
      therapy. In conclusion, we considered that this S-1 plus docetaxel combination
      therapy was effective and safe in advanced gastric cancer, and convenient for
      outpatients.

PMID- 19838025
TI  - [The efficacy of S-1 monotherapy as a 2nd/3rd-line therapy for unresectable
      recurrent colon cancer: Kanagawa conference of clinical oncology (KCCO)].
AB  - OBJECTIVE: The efficacy of S-1 as part of a 2nd/3rd-line therapy in cases of
      advanced recurrent colon cancer was studied. SUBJECTS AND METHODS: The efficacy
      of treatment with S-1 (initial dosage: 80 mg/m(2)) was studied in 19 patients
      with advanced recurrent colon cancer in whom PD was observed after pretreatment
      with 5-FU-based combination chemotherapy had been performed during the period
      from December 2003 to April 2006. Patients who underwent a course that exceeded 1
      month after the pretreatment and who met the criteria for the appropriate use of
      S-1 were selected as subjects. RESULTS: The median age was 65 years (45 to 75
      years old) with 10, 6, and 3 patients having a PS score of 0, 1, and 2,
      respectively, and the details of the duration of the pretreatment was that 12 and
      7 patients respectively received 2nd-and 3rd-line therapy. The median duration of
      the treatment with S-1 was 141 days, and the number of subjects with PR, SD, and
      PD who underwent S-1 treatment was 2, 7, and 6, respectively, with a response
      rate of 13. 3% and a disease control rate of 60. 0%. The progression free
      survival time and the overall median survival time were 5. 4 months and 13. 9
      months, respectively. Regarding the effectiveness according to treatment line,
      particularly in the subjects who were administered S-1 as part of the 2nd-line
      therapy, good results were observed, thus showing a response rate of 20% and an
      overall median survival time of 13. 9 months, which exceeded 1 year. The
      incidence of adverse events was 58%(11 and 19), and the major side effects were
      neutropenia in 31. 6% (6 and 19) and leukopenia in 21. 1% (4 and 19) of the
      patients, which are both mild and showed a grade of 2 or lower. CONCLUSION: The
      use of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon
      cancer may contribute to good prognoses.

PMID- 19838026
TI  - [Equalization of breast cancer chemotherapy at general hospital( II )-evaluation
      of safety in FEC and TC regimens].
AB  - The safety of epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) plus
      cyclophosphamide (500 mg/m(2)) (FEC75 therapy) and docetaxel (75 mg/m(2)) plus
      cyclophosphamide (600 mg/m(2)) (TC therapy) every three weeks as neoadjuvant or
      adjuvant chemotherapy was evaluated. Six or 9 patients received FEC75 or TC
      therapy, respectively. The nadir of white blood cells and neutrocyte counts in
      FEC75 and TC therapy were after 11-15 days and 8-11 days of chemotherapy,
      respectively. On the other hand, those of monocyte and reticulocyte counts were
      after 8-11 and 4-8 days for FEC75 and TC therapy, respectively. This suggests
      that there is a lag time in these parameters for the evaluation of
      myelosuppression in each chemotherapy regimen, resulting in the prediction of the
      degree of myelotoxicity by these profiles. Although 2 patients who received TC
      therapy encountered febrile neutropenia, the symptoms were improved by
      quinolones, and so granulocyte colony-stimulating factor was not needed. In
      addition, remarkable non-hematological side effects were not observed, and,
      therefore, almost all chemotherapy was performed as scheduled. From these
      results, FEC75 and TC therapy are considered to be safe.

PMID- 19838027
TI  - [Clinicopathological features of young patients with triple negative breast
      cancer].
AB  - This study investigated triple negative diagnoses that occurred in 27 (11%) out
      of 243 cases of breast cancer analyzed for the presence of estrogen receptor
      (ER), progesterone receptor( PgR), and human epidermal growth factor receptor 2
      (HER 2). In 5 of the triple negative cases of breast cancer, the patients were
      young, under 35 years of age (average age of 29). In 22 of the cases, the women
      were 35 years or older (average age of 66). The cancer quickly reoccurred in 4 of
      the 5 cases of triple negative breast cancer in young women despite various
      chemotherapy treatments, and in 3 of those cases the women died within 14 months
      following surgery. Even in statistical analysis, triple negative breast cancer in
      young women has a significantly poorer prognosis for both disease-free survival
      rate and overall survival rate, compared with triple negative breast cancer in
      women 35 and older, and young women without triple negative breast cancer. When
      basal-like phenotype was defined as being positive for epidermal growth factor
      (EGFR) and/or cytokeratin (CK)5/6, among the triple negative breast cancer cases
      of women 35 years and older, the rate for basal-like phenotype, which is said to
      have a poor prognosis, was 67% (14 out of 21 cases) while in young women with
      triple negative breast cancer, all cases (5 out of 5) were basal-like phenotype.
      This suggests that the biological degree of malignancy is extremely high for
      young women with triple negative breast cancer.

PMID- 19838028
TI  - [Efficacy and safety of continuous subcutaneous injection of the compound
      oxycodone in cancer pain management: the first 4-year audit].
AB  - The compound oxycodone injection, but not pure oxycodone, has been available
      since the 1920's in Japan. The compound, containing oxycodone and hydrocotarnine,
      can be subcutaneously administered. Hydrocotarnine is a non-narcotic opium
      alkaloid. Nowadays, along with the increase in the prescription frequency of oral
      oxycodone, the compound oxycodone injection is regarded as an important
      alternative in palliative care. However, few clinical reports about this drug
      have been documented in Japan. We have intensively introduced the compound for
      cancer pain control since 4 years ago and we report a study on the safety and
      efficacy of the continuous subcutaneous administration of the compound injection.
      Ninety-seven patients were naively administered the compound for cancer pain
      control and the mean administered period was 18. 0+/-15. 5 days. 61. 9% of all
      cases were switched from oral oxycodone. The efficacy in cancer pain control was
      evaluated for the first two weeks using a numeric rating scale (NRS: 0, no pain,
      and 10, imaginary worst ). They had statically shown pain control improvement
      from 6. 8+/-2. 8 on administration to 2. 4+/-2. 5 one week later, 1. 7+/-1. 9 two
      weeks later, and 2. 3 +/-2. 6 on the last observation day of the study (p<0.
      001). One week later on administration, no significant adverse effects were found
      in the serology, conscious level, and subjective symptoms of nausea and vomiting.
      But adverse effects difficult to manage were experienced in 7. 2%, including
      delirium, constipation, nausea and vomiting, vertigo, and local skin toxicity on
      the injected site. All episodes were experienced within 16 days of compound
      administration, which had been followed by switching to fentanyl or subcutaneous
      morphine injection. The conversion ratio from compound oxycodone injection to
      oral oxycodone was 1. 43 without adjustment required(n=35). We speculate that the
      compound can be regarded as a pure oxycodone injection using continuous
      subcutaneous administration. While our clinical audit is a primitive one, we may
      conclude that the continuous subcutaneous administration of the compound
      oxycodone injection should be effective and safe in clinical use for cancer pain
      control.

PMID- 19838029
TI  - [Assessment of chemotherapy-induced nausea and vomiting(CINV)using MASCC
      antiemesis tool].
AB  - Chemotherapy-induced nausea and vomiting (CINV) is one of the side effects
      causing significant psychological and physical suffering in patients receiving
      chemotherapy. Because CINV often impairs patients' quality of life and leads to
      cessation of treatments, antiemetic therapy has been thought important. Recently,
      the development of new antiemetic agents and the antiemetic guidelines provided
      by ASCO, NCCN, and MASCC etc. allow us to palliate CINV with appropriate
      antiemetic therapy. For appropriate antiemetic therapy, the patient must obtain
      accurate CINV information, particularly regarding whether it will be acute or
      delayed. MASCC first developed and posted the MASCC Antiemesis Tool (MAT) in
      2004. The MAT is an eight-term scale for the assessment of acute and delayed
      nausea and vomiting, and is completed once per chemotherapy course. Although it
      is now validated in the US and UK and used worldwide, few reports have been
      available in Japan to use assessment tools including the MAT for acute and
      delayed CINV. We prospectively investigated the utility of the MAT. Fifteen
      ambulatory patients with breast cancer were subjected to evaluation, aged 29 to
      73(median 58)years. In the results, the MAT allowed us to easily find patients
      treated with inappropriate antiemetic therapy. At the same time, it was easy to
      determine acute or delayed CINV, resulting in more appropriate treatment. The
      scale questions were unfamiliar to patients, but they clearly understood by means
      of a detailed explanation. Thus, it was suggested that the MAT is useful to
      assess antiemetic therapy. Consequently, it could contribute to completion of the
      chemotherapy.

PMID- 19838031
TI  - [Cancer therapy analysis from the viewpoint of DPC data].
AB  - DPC (Diagnosis Procedure Combination), Japanese specific prospective payment
      system, is gradually taking root in Japan. Hospitals under this system are
      required to submit nationally standardized electronic data to get reimbursed. DPC
      data include not only information for reimbursement but also details of medical
      records of each patient. We have tried to investigate actual situation of cancer
      treatment in Japan by analyzing DPC data. In this study, we have revealed actual
      situation of non-small cell lung cancer treatment in both Osaka prefecture and
      nationwide using girasol , the DPC-analysis-system, by Medical Architects Inc.
      Moreover, we report the significant variations in non-small cell lung cancer
      chemotherapy regimens and therapy protocols between the two hospitals in Osaka
      prefecture.

PMID- 19838030
TI  - [Revision of the informed consent form for patients based on investigation of
      adverse events of mFOLFOX6 regimen].
AB  - We retrospectively investigated the frequency and severity of adverse events in
      124 patients with colorectal cancer who were treated by mFOLFOX6 regimen from
      August, 2005 to December, 2006. The incidences of grade 3/4 adverse events were;
      leucopenia 16%, neutropenia 40%, anemia 11%, thrombocytopenia 7%, febrile
      neutropenia 7%, nausea 3%, vomiting 2%, anorexia 2%, diarrhea 4%, fatigue 7%, and
      alopecia 0%. The incidences of all grades and grade 3/4 hypersensitivity reaction
      were 35% and 4%, and the median number of course when it firstly appeared was
      6(range, 1-21). The incidences of all grade and grade 3 peripheral sensory
      neuropathy were 74% and 6%, and the median number of course when it firstly
      appeared 11(range, 6-16). The incidences of adverse events in this cohort were
      similar or lower than those reported in Western countries. Our investigation
      shows that mFOLFOX6 regimen is tolerable in clinical practice in Japan. The
      informed consent form was revised based on these results. The incidences of
      adverse events were renewed to provide useful information and improve self-care
      ability. The symptoms and the time to appearance of the hypersensitivity reaction
      and peripheral sensory neuropathy were added. We think it is important to provide
      the information based on the clinical practice.

PMID- 19838032
TI  - [Successful treatment results of S-1 administration in 2 patients, one with a
      remnant tumor of the larynx and metastatic tumors to the lung, and another with a
      metastatic tumor in the neck from the hypopharynx].
AB  - We report two successful remnant and recurrent cases of head and neck cancer
      treated with S-1. Case 1, a 52-year-old man, was diagnosed as supraglottic
      laryngeal carcinoma (T3N2cM0, squamous cell carcinoma: SCC) on January 25, 2000,
      and concurrent chemoradiotherapy (CCRT) was applied. After the treatment, a
      remnant tumor in the larynx was found by biopsy. He was followed using UFT at
      400mg/day because he had refused surgery. Pulmonary metastasis was detected by
      chest CT on June 14, 2001, and the administration of S-1 was started. After 2
      courses, the mass in the lung disappeared, and the primary lesion was also judged
      to be a complete response(CR). The administration of S-1 is still continuing and
      remnant tumors have not been found. Case 2, a 76-year-old man, was diagnosed with
      hypopharyngeal carcinoma (T3N2bM0, SCC) on December 14, 2001, and CCRT was
      applied resulting in CR in the hypopharynx and the neck. He was followed using
      UFT at 300 mg/day after discharge. A supraclavicular lymph node became palpable
      on March 27, 2003. Pathological examination by fine needle aspiration cytology
      showed SCC, class V. After 2 courses administering S-1 at 100mg/day, the
      supraclavicular lymph node disappeared. S-1 was changed to UFT at 300 mg/day on
      July 31, 2003, because adverse events of grade 3 appeared. Administration of UFT
      was continued for one year. No recurrence has been found for 5 years.

PMID- 19838033
TI  - Small-cell lung cancer arising after chemotherapy for a patient with lymphoma of
      pulmonary mucosa-associated lymphoid tissue-a case report.
AB  - A 76-year-old woman was admitted to our hospital with infiltrations evident in
      the right lower lobe on chest computed tomography. Bronchoscopic biopsy showed
      lymphoma of mucosa-associated lymphoid tissue (MALT). Lymphoma of the pulmonary
      MALT became enlarged at 8 months after diagnosis and dyspnea developed. Four
      courses of chemotherapy(rituximab+ cladribine)resulted in a partial response.
      However, 14 months after the chemotherapy, she developed multiple lung and liver
      tumors accompanied by disseminated intravascular coagulation syndrome. A
      histological examination of bone marrow aspiration showed small cell carcinoma.
      We administered one course of carboplatin and etoposide, but bone marrow
      suppression was so severe that further chemotherapy was precluded. To our
      knowledge, this is a rare case of small cell lung cancer arising from the
      treatment of lymphoma of pulmonary MALT.

PMID- 19838034
TI  - [Two cases of recurrent non-small cell lung cancer successfully treated with S-1
      as fifth-line chemotherapy].
AB  - There is at present no defined role for S-1 chemotherapy in patients with
      advanced non-small cell lung cancer (NSCLC) who previously failed chemotherapy.
      Two cases of multidrug-resistant, NSCLC that were successfully treated with S-1
      as fifth-line chemotherapy are reported. A 75-year-old man was diagnosed as
      having pulmonary adenocarcinoma, cT1N3M0, stage III B. He was treated with S-1 as
      fifth-line chemotherapy after treatment with cisplatin(CDDP)and vinorelbine(VNR),
      docetaxel (DOC), gemcitabine (GEM) and VNR, and amrubicin (AMR). After completing
      two courses, chest computed tomography(CT)showed a partial response( PR)of the
      recurrent tumors, and the serum carcinoembryonic antigen level decreased.
      Currently, seven courses have been completed, and this treatment will be
      continued due to the tumor response of stable disease. A 65-year-old woman was
      referred for treatment of recurrent pulmonary adenocarcinoma after right upper
      lobe resection. She was treated with S-1 as fifth-line chemotherapy after
      treatment with GEM and VNR, carboplatin(CBDCA) and paclitaxel ( PTX), DOC, and
      gefitinib. After completing five courses, chest CT showed PR of the
      intrapulmonary metastases. Though grade 3 toxicity-anemia in the first case and
      an elevated serum amylase level in the second case were observed in both cases,
      the patients' quality of life was preserved. S-1 could therefore be a treatment
      option for patients with advanced NSCLC who previously underwent chemotherapy
      unsuccessfully.

PMID- 19838035
TI  - [A case of recurrent rectal cancer with multiple lung metastases successfully
      treated with S-1 and CPT-11 combination chemotherapy].
AB  - We report a case of recurrent rectal cancer with multiple lung metastases
      successfully treated with S-1 and CPT-11 combination chemotherapy. Rectal
      amputation was carried out on the rectal cancer patient, a 63-year-old man. CT
      scan revealed multiple lung metastases after 20 months of surgery. The patient
      was treated with S-1 and CPT-11 combination chemotherapy. S-1(100mg/body/day)was
      orally administered for 2 weeks followed by a 1-week interval, and CPT-11 (120
      mg/body on day 1)was simultaneously administered. After completion of 8 courses,
      CT scan showed no lung metastases, and the patient was judged to have achieved a
      complete response (CR). The CR interval was maintained for twelve months until 20
      courses of chemotherapy had been completed. This chemotherapy was expected to
      have a potent therapeutic efficacy for recurrent rectal cancer, considering the
      convenience, cost benefit and no severe adverse event.

PMID- 19838036
TI  - [A case of non-small cell lung cancer treated safely by whole brain radiation
      therapy and erlotinib].
AB  - In December 2006, a 55-year-old-man was given a diagnosis of adenocarcinoma of
      the lung with multiple brain metastases. Systemic chemotherapy was given
      consisting of carboplatin plus paclitaxel and carboplatin plus gemcitabine. But
      with the increase of the brain metastases, he was admitted in February 2008. He
      received whole brain radiation therapy and was given erlotinib at the same time.
      The brain metastases disappeared and primary lung tumor decreased after the start
      of therapy. No side effect was observed. Although further investigations are
      needed to completely determine the efficacy of this treatment procedure, it seems
      clear that combining erlotinib with radiation therapy produces a synergy effect
      on the cancer.

PMID- 19838037
TI  - [A case of recurrent pancreatic cancer with lung metastasis responding to S-1
      combined gemcitabine chemotherapy].
AB  - The patient was a 54-year-old male. In July 2004, he underwent resection of the
      pancreatic body tail region to treat pancreatic body tail cancer. On
      histopathological examination, the stump of the extirpated specimen was positive
      for tumor cells. After surgery, 10 courses of therapy with gemcitabine
      hydrochloride(GEM, 1, 000 mg/m(2), 3-week administration followed by 1-week
      discontinuation)were performed, and follow-up was continued. In February 2006,
      local relapse was detected. Chemotherapy with GEM was administered for 1 year and
      9 months. However, in November 2007, an increase in the recurrent lesion size and
      right lung metastasis were noted. The regimen was switched to combination therapy
      with S-1 and GEM(S-1 60 mg/m(2) day, continuous administration on days 1 to 14
      and 2-week discontinuation; and GEM 1, 000 mg/ m(2), administered on days 8 and
      15). After the end of the 11th course, PET-CT revealed the disappearance of FDG
      accumulation in the recurrent and metastatic lesion sites. During the treatment
      period, there were no grade 3 or higher adverse reactions. The patient is being
      treated at the outpatient clinic (as of January 2009).

PMID- 19838038
TI  - [A case of small cell undifferentiated carcinoma of the esophagus successfully
      treated by chemoradiotherapy].
AB  - Small cell carcinoma of the esophagus is rare, with a poor prognosis, and there
      is currently no standard therapy. Here we report a case of small cell carcinoma
      of the esophagus with right supraclavicular lymph node metastasis which was
      successfully treated by chemoradiotherapy. A 55-year-old man was admitted to our
      hospital with a right-sided neck tumor. The neck tumor was diagnosed as a small
      cell carcinoma by aspiration cytology. Endoscopy revealed an irregular tumor in
      the middle thoracic esophagus, 31 cm from the upper incisor teeth, but malignant
      cells were not detected from an esophageal biopsy. Right supraclavicular lymph
      node metastasis was detected by computed tomography and positron emission
      tomography computed tomography, and aspiration cytology revealed small cell
      undifferentiated carcinoma cells. The patient was diagnosed with a small cell
      carcinoma of the esophagus with supraclavicular lymph node metastasis, stage III:
      T2N3M0. Concurrent chemoradiotherapy using 5-fluorouracil and cisplatin was
      started. Lymph node reduction occurred from day 3, and endoscopy two months after
      chemoradiotherapy showed only a scar. We diagnosed the patient in complete
      remission, and he continues to do well with a recurrence-free status of 14 months
      after initial chemoradiotherapy.

PMID- 19838039
TI  - [A case of gastric cancer with peritoneal dissemination who achieved long
      survival by successive treatments with S-1 in combination with CDDP, paclitaxel
      and irinotecan].
AB  - The patient was a 63-year-old male with multiple peritoneal disseminations of
      advanced gastric cancer. He underwent chemotherapy with a combination of S-1 120
      mg/day (3 weeks administration and 2 weeks rest) and cisplatin (CDDP) 60 mg/m(2)
      (day 8). After 3 courses of this regimen, CT revealed no evidence of ascites. He
      then underwent laparatomy. Peritoneal dissemination appeared, and the findings
      were sT3, N0, H0, P1, CY1, M1(PLE), sStage IV. A bypass operation was performed.
      As second-line chemotherapy, he received combination chemotherapy with S-1 and
      paclitaxel (PTX) 60 mg/m(2) (div), 20 mg/m(2) ( ip) (day 1, 8). However, he
      complained of ascites after 16 courses. We tried weekly administration of PTX and
      tri-weekly administration of irinotecan (50 mg/m(2)) with S-1. This treatment was
      successfully continued for 20 courses. The adverse effect was anemia (grade 2).
      He died two years eight months after surgery. The chemotherapy with S-1/CDDP, S
      1/PTX, and S-1/PTX/irinotecan was thought to be effective for advanced gastric
      cancer with peritoneal dissemination.

PMID- 19838040
TI  - [A case of recurrent gastric cancer during adjuvant chemotherapy with S-1,
      treated by S-1 combination chemotherapy].
AB  - A 59-year-old man was admitted to our hospital for the treatment of gastric
      cancer with synchronous and multiple metastatic liver tumors. After total
      gastrectomy in February 2005, partial resection of the posterior segment of the
      liver was carried out in the next month. Pathological study of both the resected
      specimens showed moderately differentiated adenocarcinoma. The postoperative
      treatment with S-1 was initiated without any evidence of recurrence. However, CT
      scans showed recurrent multiple liver tumors after 4 courses of treatment with S
      1. Subsequently, a combination chemotherapy of S-1 (80 mg/m(2) over day 1-14 with
      a 2-week rest) and paclitaxel (PTX) (120 mg/m(2), day 1 and 15) was applied.
      After 3 courses, CT scans showed reduced liver metastases, judged as a partial
      response(PR)on Response Evaluation Criteria in Solid Tumors (RECIST). However,
      metastatic liver tumors showed progressive disease (PD) after 7 courses of
      treatment. The treatment was changed to combination chemotherapy with S-1 (80
      mg/m(2) over day 1-21 with a 2-week rest) and CPT-11 (80 mg/m(2) day, day 1 and
      15) for 6 courses, but the legions showed PD. He was then treated with combined
      chemotherapy with S-1 (70 mg/m(2) over day 1-14 with a 1-week rest)and cisplatin
      (CDDP) (10 mg/m(2), day 1 and 8). However, his condition became worse and he was
      treated at the palliative care unit. There were no adverse effects greater than
      grade 4 throughout the treatment period, and his treatment was continued as an
      outpatient for more than two years. This case suggests that after failure of S-1
      therapy, S-1 combination chemotherapy might be an effective treatment for
      recurrent gastric cancer.

PMID- 19838041
TI  - [A case of advanced gastric cancer effectively treated on an outpatient basis by
      biweekly S-1 and docetaxel combination chemotherapy].
AB  - A 70-year-old male patient had advanced gastric cancer with severe lymph node
      metastasis. He was treated by combination chemotherapy of S-1 120 mg/body (1-week
      administration and 1-week rest)and docetaxel (DOC) 40 mg/body( day 1 and 15).
      After 2 courses of treatment, the primary lesion was remarkably improved and para
      aortic lymph nodes disappeared by CT scan, so we diagnosed it as a partial
      response (PR). Anemia (WHO grade 3) was observed as toxicity and treated with
      transfusion. This regimen could be performed on an outpatient basis for over 2
      years, and the response was maintained on CT and endoscopic examination after 20
      courses of treatment. The biweekly docetaxel and S-1 combination chemotherapy was
      thought to be an effective method as chemotherapy for an outpatient with advanced
      gastric cancer.

PMID- 19838042
TI  - [A case of unresectable hilar bile duct cancer responding to chemo-radiotherapy
      by gemcitabine].
AB  - A 66-year-old woman was admitted to our hospital because of general fatigue and
      icterus. PTC findings showed irregular stenosis of hilar bile duct. Abdominal CT
      scan showed a dilatation of the intra-hepatic bile duct and a tumor around hilar
      bile duct. We diagnosed it as hilar bile duct carcinoma, and although we operated
      it was unresectable because of the metastasis of a para-aorta lymph node and
      duodenal invasion. We started chemo-radiotherapy with a total dose of 45 Gy and
      gemcitabine. The tumor and para-aorta lymph node were remarkably decreased, and
      tumor marker CA 19-9 was also decreased to within the normal range. The patient
      had a peritoneal dissemination 10 months after the chemo-radiotherapy and
      survived 20 months.

PMID- 19838043
TI  - [A case of interstitial pneumonia induced by gemcitabine hydrochloride for
      unresectable bile duct cancer].
AB  - A 78-year-old man was admitted for obstructive jaundice and unresectable bile
      duct cancer on March 4, 2008. Since biliary drainage was extremely difficult, he
      began 2 treatment courses of gemcitabine hydrochloride (GEM 800 mg/m(2) on days
      1, 8, 15 every 4 weeks). He suffered from dry cough and dyspnea on May 13, 2008.
      He was diagnosed as GEM-induced interstitial pneumonia with severe hypoxemia by
      CT scan and arterial blood gas examination. He recovered with two courses of
      steroid pulse therapy, diuretics and antibiotics. Alternatively, he was given
      oral S-1 ( 80 mg/m(2) 4 weeks on and 2 weeks off) from June 12, 2008. His QOL was
      well kept without jaundice for as long as a half year. This is the first report
      of GEM-induced interstitial pneumonia in bile duct cancer. In conclusion,
      interstitial pneumonia must be taken into consideration as a rare adverse
      reaction when GEM is used for biliary neoplasms.

PMID- 19838044
TI  - [A case of advanced hepatocarcinoma responding to combination therapy of S-1 and
      PEG-IFN].
AB  - A57 -year-old man. Though chronic hepatitis C was pointed out before, it had been
      left untreated for about 5 years. He was hospitalized because many venereal
      diseases had been pointed out in the liver by abdomen ultrasonography. Results of
      close examination revealed stage IV B with bone metastases, and pulmonary
      metastases was diagnosed. After consultation, whole-body chemotherapy combining S
      1 and PEG-IFN was attempted as of June 26, 2007. S-1 (80 mg/day) was then
      administered every day for two weeks with drug withdrawal for one week. PEG
      IFNalpha-2a (180 microg)was administered once a week. We set three weeks as one
      course. The liver tumor was markedly reduced, and the pulmonary metastases were
      also reduced at the completion of 5 courses. The therapeutic effectiveness of
      this chemotherapy was confirmed by imaging test. The course was favorable, and
      whole-body chemotherapy was discontinued on January 29, 2008. At this writing in
      October of 2008, the course has been uneventful. This treatment method is a
      promising choice for whole-body chemotherapy for advanced hepatocarcinoma in the
      future. We have added some review of the literature, and the S-1+PEG-IFN
      combination chemotherapy is reported.

PMID- 19838045
TI  - [A case of liver metastasis of rectal cancer, refractory to previous
      chemotherapy(5-FU/LV, irinotecan, oxaliplatin) responding to bevacizumab combined
      with FOLFIRI chemotherapy].
AB  - The case was a 69-year-old man with liver metastasis who had relapsed after the
      resection of rectal cancer. We treated the patient with
      FOLFIRI+bevacizumab(BV)after the failure of S-1+CPT-11, radiation, UFT/LV, FOLFOX
      and FOLFIRI regimen. The tumor marker level and accumulation of FDG-PET were
      rapidly decreased after initiating FOLFIRI+BV. There was no serious adverse
      event, and a remarkable improvement of QOL was observed. This case suggests that
      the BV combination regimen is useful even after the failure of FOLFOX and FOLFIRI
      regimen.

PMID- 19838046
TI  - [A successfully resected case of liver metastasis of gastrointestinal stromal
      tumor responding to neoadjuvant chemotherapy with imatinib mesylate and
      interventional radiology].
AB  - A 75-year-old woman underwent resection of gastrointestinal stromal tumor (GIST)
      of small intestine in 1999. In January 2006, she suffered liver dysfunction and
      abdominal CT revealed she had a large liver metastasis. At first the tumor in the
      right lobe progressed to the medial segment and seemed unresectable. She twice
      underwent transarterial embolization and treatment with 400mg/day of imatinib
      mesylate. Then percutaneous transhepatic portal embolization was performed. As a
      result, liver metastasis markedly decreased in size, and extended right lobectomy
      of the liver was performed in June 2006. A large portion of the liver metastasis
      showed necrosis, but histopathological examination revealed focal remnants of
      viable tumor cells. In March 2007, radiofrequency ablation was performed for
      recurrence of remnant liver. The patient has been treated by imatinib mesylate
      and is alive with no evidence of tumor recurrence.

PMID- 19838047
TI  - A genomic strategy for predicting androgen receptor activity in prostate tumors.
AB  - Mendiratta et al. have developed an AR signature for prostate cancer that is
      based on the expression of 300 genes. The AR signature is decreased with androgen
      deprivation therapy, and in the development of androgen independent prostate
      cancer, however significant inter-individual variation in AR activity was noted.
      Decreased AR activity was also related to the expression of SRC kinase, and
      sensitivity to dasatinib. The work by Mendiratta et al. may be useful to
      determine the AR status of tumors in order to inform therapy and individualize
      treatment.

PMID- 19838048
TI  - SKAnking with Ska3: essential role of Ska3 in cell division revealed by combined
      phenotypic profiling.

PMID- 19838049
TI  - Basis for immunization recommendations among countries of the worldHealth
      Organization European region.
AB  - Despite World Health Organization (WHO) goals to reduce the incidence of several
      vaccine preventable diseases across the European region, the adoption of new
      vaccines has been slower than expected. To identify factors that influence the
      decision to recommend new vaccines, especially hepatitis B and Haemophilus
      influenzae, type b (Hib) vaccines, we studied the factors used in immunization
      decision-making across this region. A structured questionnaire was sent to the
      Immunization Program Manager of each country with the option to return the
      completed survey by e-mail, fax or complete a web-based survey. Frequency
      distributions were explored for all survey items. Bivariate analysis was
      conducted to assess differences between countries by economic status. Of the 47
      (89%) countries responding, the majority reported vaccine safety (91%),
      epidemiology of disease (85%), and the severity of disease prevented (74%) as
      very important factors when making immunization recommendations. Half of the
      countries reported the cost of disease burden and cost-effectiveness data were
      very important financial information when implementing vaccine recommendations.
      While no significant difference was seen by economic status in countries
      recommending hepatitis B vaccine (p = 0.1129), high economic status countries
      were significantly more likely to report Hib vaccine is part of the country's
      recommended schedule (p = 0.0011). Understanding the importance of the factors
      considered by countries when making national immunization recommendation
      decisions can aid public health experts in providing countries with information
      needed to support these decisions.

PMID- 19838050
TI  - Kinship in the SRP RNA family.
AB  - The signal recognition particle (SRP) is a ribonucleoprotein complex which
      participates in the targeting of protein to cellular membranes. The RNA component
      of the SRP has been found in all domains of life, but the size of the molecule
      and the number of RNA secondary structure elements vary considerably between the
      different phylogenetic groups. We continued our efforts to identify new SRP RNAs,
      compare their sequences, discover new secondary structure elements, conserved
      motifs, and other properties. We found additional proof for the variability in
      the apical loop of helix 8, and we identified several bacteria which lack all of
      their SRP components. Based on the distribution of SRP RNA features within the
      taxonomy, we suggest seven alignment groups: Bacteria with a small (4.5S) SRP
      RNA, Bacteria with a large (6S) SRP RNA, Archaea, Fungi (Ascomycota), Metazoa
      group, Protozoa group, and Plants. The proposed divisions improve the prediction
      of more distantly related SRP RNAs and provide a more inclusive representation of
      the SRP RNA family. Updates of the Rfam SRP RNA sequence collection are expected
      to benefit from the suggested groupings.

PMID- 19838051
TI  - p53 sumoylation: mechanistic insights from reconstitution studies.
AB  - Sumoylation represents a cascade of enzymatic reactions mediated by SUMO
      activating enzyme (SAE1/SAE2 heterodimer), SUMO-conjugating enzyme Ubc9, and SUMO
      E3 ligases that include five protein inhibitors of activated STATs (PIAS1, PIAS3,
      PIASy, PIASxalpha and PIASxbeta), and culminates in the formation of an
      isopeptide bond between the C-terminal glycine of a small ubiquitin-related
      modifier (SUMO) and the lysine residue of a protein substrate. Conjugation of a
      SUMO moiety, ranging from 92 (for SUMO-2) to 97 (for SUMO-1) amino acids, not
      only increases the molecular size but also alters the property and function of
      the modified protein. Although sumoylation has been observed with many cellular
      proteins and the majority of transcription factors including the p53 tumor
      suppressor, this covalent modification is normally detectable only in a small
      population, often less than 5%, of a given substrate in vivo. This low abundance
      of SUMO-modified proteins, due to the presence of sentrin/SUMO-specific proteases
      (SENPs) that actively cleave the reversible SUMO linkage, has posed a challenge
      to define the biological effect of SUMO in living cells. Nevertheless, the recent
      development of reconstituted modification and chromatin-dependent transcription
      assays has provided unique insights into the molecular action of SUMO in
      modifying protein function. The availability of these reconstitution systems has
      unraveled the interplay between sumoylation and acetylation in regulating the DNA
      binding and transcriptional activity of p53 tetramers and further allow the
      identification of transcriptional corepressors, such as mSin3A, CoREST1/LSD1 and
      Mi-2/NuRD implicated in SUMO-dependent gene silencing events.

PMID- 19838052
TI  - Sex chromosome inactivation in the male.
AB  - Mammalian females have two X chromosomes, while males have only one X plus a Y
      chromosome. In order to balance X-linked gene dosage between the sexes, one X
      chromosome undergoes inactivation during development of female embryos. This
      process has been termed X-chromosome inactivation (XCI). Inactivation of the
      single X chromosome also occurs in the male, but is transient and is confined to
      the late stages of first meiotic prophase during spermatogenesis. This phenomenon
      has been termed meiotic sex chromosome inactivation (MSCI). A substantial portion
      ( approximately 15-25%) of X-linked mRNA-encoding genes escapes XCI in female
      somatic cells. While no mRNA genes are known to escape MSCI in males,
      approximately 80% of X-linked miRNA genes have been shown to escape this process.
      Recent results have led to the proposal that the RNA interference mechanism may
      be involved in regulating XCI in female cells. We suggest that some MSCI-escaping
      miRNAs may play a similar role in regulating MSCI in male germ cells.

PMID- 19838053
TI  - A possible crosstalk between DNA repair pathways and angiogenesis.

PMID- 19838054
TI  - Spindle assembly checkpoint, aneuploidy and tumorigenesis.

PMID- 19838055
TI  - Guarding the guardian: Mdmx plays important roles in setting p53 basal activity
      and determining biological responses in vivo.

PMID- 19838056
TI  - Caspase-8 as a potential mediator of pro-tumorigenic signals.

PMID- 19838057
TI  - BRCA2: Shining light on the regulation of DNA-binding selectivity by RAD51.

PMID- 19838058
TI  - The Pso4 complex splices into the DNA damage response.

PMID- 19838059
TI  - Turning on the beta-cell identity in the pancreas.

PMID- 19838060
TI  - Aurora B kinase, an immobile passenger!

PMID- 19838061
TI  - Modification of survival pathway gene expression in human breast cancer cells by
      tetraiodothyroacetic acid (tetrac).
AB  - Tetraiodothyroacetic acid (tetrac) inhibits the cellular actions of thyroid
      hormone initiated at the hormone receptor on plasma membrane integrin
      alphavbeta3. Via interaction with the integrin, tetrac is also capable of
      inhibiting the angiogenic effects of vascular endothelial growth factor and basic
      fibroblast growth factor. MDA-MB-231 cells are estrogen receptor-negative human
      breast cancer cells shown to be responsive to tetrac in terms of decreased cell
      proliferation. Here we describe actions initiated at the cell surface receptor by
      unmodified tetrac and nanoparticulate tetrac on a panel of survival pathway genes
      in estrogen receptor-negative human breast cancer (MDA-MB-231) cells.
      Nanoparticulate tetrac is excluded from the cell interior. Expression of
      apoptosis inhibitors XIAP (X-linked inhibitor of apoptosis) and MCL1 (myeloid
      cell leukemia sequence 1) was downregulated by nanoparticulate tetrac in these
      breast cancer cells whereas apoptosis-promoting CASP2 and BCL2L14 were
      upregulated by the nanoparticulate formulation. Unmodified tetrac affected only
      XIAP expression. Expression of the angiogenesis inhibitor thrombospondin 1
      (THBS1) gene was increased by both formulations of tetrac, as was the expression
      of CBY1, a nuclear inhibitor of catenin activity. The majority of differentially
      regulated Ras-oncogene family members were downregulated by nanoparticulate
      tetrac. The latter downregulated expression of epidermal growth factor receptor
      gene and unmodified tetrac did not. Nanoparticulate tetrac has coherent anti
      cancer actions on expression of differentially-regulated genes important to
      survival of MDA-MB-231 cells.

PMID- 19838062
TI  - p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of
      apoptosis by RITA.
AB  - Thioredoxin reductase 1 (TrxR1) is a key regulator in many redox-dependent
      cellular pathways, and is often overexpressed in cancer. Several studies have
      identified TrxR1 as a potentially important target for anticancer therapy. The
      low molecular weight compound RITA (NSC 652287) binds p53 and induces p53
      dependent apoptosis. Here we found that RITA also targets TrxR1 by non-covalent
      binding, followed by inhibition of its activity in vitro and by inhibition of
      TrxR activity in cancer cells. Interestingly, a novel approximately 130 kDa form
      of TrxR1, presumably representing a stable covalently linked dimer, and an
      increased generation of reactive oxygen species (ROS) were induced by RITA in
      cancer cells in a p53-dependent manner. Similarly, the gold-based TrxR inhibitor
      auranofin induced apoptosis related to oxidative stress, but independently of p53
      and without apparent induction of the approximately 130 kDa form of TrxR1. In
      contrast to the effects observed in cancer cells, RITA did not inhibit TrxR or
      ROS formation in normal fibroblasts (NHDF). The inhibition of TrxR1 can sensitize
      tumor cells to agents that induce oxidative stress and may directly trigger cell
      death. Thus, our results suggest that a unique p53-dependent effect of RITA on
      TrxR1 in cancer cells might synergize with p53-dependent induction of pro
      apoptotic genes and oxidative stress, thereby leading to a robust induction of
      cancer cell death, without affecting non-transformed cells.

PMID- 19838063
TI  - PKR is not a universal target of tumor suppressor p53 in response to genotoxic
      stress.
AB  - It has been recently reported that p53 activation can lead to the induction of
      PKR-eIF2alpha phosphorylation pathway. However, we demonstrate that PKR and
      eIF2alpha phosphorylation at serine 51 are not downstream of p53 in response to
      doxorubicin treatment suggesting that PKR is not a universal target of p53 as
      proposed.

PMID- 19838064
TI  - Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity.
AB  - Kinesin-like proteins are integral to formation and function of a conserved
      mitotic spindle apparatus that directs chromosome segregation and precedes cell
      division. Ubiquitous to the mechanism of spindle assembly and stability are
      balanced Kinesin-5 promoting and Kinesin-14 opposing forces. Distinct Kinesin-14
      roles in bipolarity in eukaryotes have not been shown, but are suggested by gamma
      tubulin-based pole interactions that affect establishment and by microtubule
      cross-linking and sliding that maintain bipolarity and spindle length. Distinct
      roles also imply specialized functional domains. By cross-species analysis of
      compatible mechanisms in establishing mitotic bipolarity we demonstrate that
      Kinesin-14 human HSET (HsHSET) functionally replaces Schizosaccharomyces pombe
      Pkl1 and its action is similarly blocked by mutation in a Kinesin-14 binding site
      on gamma-tubulin. Drosophila DmNcd localizes preferentially to bundled interpolar
      microtubules in fission yeast and does not replace SpPkl1. Analysis of twenty-six
      Kinesin-14 derivatives, including Tail, Stalk or Neck-Motor chimeras, for spindle
      localization, spindle assembly and mitotic progression defined critical domains.
      The Tail of SpPkl1 contains functional elements enabling its role in spindle
      assembly that are distinct from but transferable to DmNcd, whereas HsHSET
      function utilizes both Tail and Stalk features. Our analysis is the first to
      demonstrate distinct mechanisms between SpPkl1 and DmNcd, and reveal that HsHSET
      shares functional overlap in spindle pole mechanisms.

PMID- 19838065
TI  - MicroRNAs: Crucial multi-tasking components in the complex circuitry of tumor
      metastasis.
AB  - Distant metastases are the underlying cause of patient mortality in an
      overwhelming majority of human carcinomas. Certain microRNAs have recently been
      found capable of regulating the process of tumor metastasis. In this review, we
      highlight advances within this rapidly emerging field, endeavor to connect known
      microRNA pathways with recent conceptual advances in the larger field of
      metastasis research, and speculate regarding the future utility of microRNAs in
      the diagnosis and treatment of human cancers. Assessed collectively, current
      evidence suggests that the pleiotropic activities of microRNAs endow them with
      the capacity to function as crucial, yet previously unappreciated, nodes within
      already-identified metastasis regulatory circuitry. This has important
      implications for our understanding of the pathogenesis of high-grade
      malignancies.

PMID- 19838066
TI  - Foxp3-expressing T regulatory cells and mast cells in acute graft-versus-host
      disease of the skin.
AB  - Acute graft-versus-host disease (aGVHD) limits the effectiveness of allogeneic
      hematopoietic stem cell transplantation. Foxp3 is required for the development
      and function of CD4(+)/CD25(+) regulatory T cells (T-regs). Foxp3-expressing T
      regs are thought to protect against GVHD. Mast cells are thought to be essential
      in CD4(+)/CD25(+) regulatory T cell-dependent peripheral tolerance. Twenty
      biopsies of skin with grades I-III aGVHD were stained for Foxp3 and CD117.
      Inflammation was quantified by a 4 point scale, 0 = no inflammation, 1 = <25% of
      20x field, 2 = 25-50%, and 3 = >50%. T-regs and mast cells were quantified by a 4
      point scale, 0 = no cells per 20x field, 1 = <5 cells per 20x field, 2 = 5-10
      cells, and 3 = >10 cells. T-regs were positively correlated with both
      inflammation and aGVHD grade. Twelve cases with low T-regs had mild inflammation
      and lower grades of aGVHD and 6 cases with high T-regs had dense inflammatory
      infiltrate and higher grades of aGVHD. The number of T-regs, mast cells and
      density of the inflammatory infiltrate were positively correlated only in cases
      with mild inflammation. In aGVHD of the skin, T-regs increased with the degree of
      inflammation and GVHD grade. Mast cells were present at the same density whether
      aGVHD was of lower or higher grade.

PMID- 19838067
TI  - Mechanisms of epigenetic inheritance: copying of polycomb repressed chromatin.
AB  - A key problem in gene regulation is how transcription patterns can be stably
      maintained in dividing cells. The formation and propagation of chromatin
      structures is believed to underlie stable gene expression patterns, including
      those maintained by Polycomb Group proteins. Recent studies focused on how
      Polycomb Group proteins and the chromatin structures they create behave during
      DNA replication and have begun to shed light onto mechanisms by which chromatin
      structures may be propagated through S-phase. These studies suggest that both
      segregation of chromatin features to newly replicated chromatin and a feedback
      loop consisting of histone modification and recognition of this modification may
      contribute to inheritance. Results are discussed in light of other links between
      Polycomb proteins and DNA replication, and other systems in which maintenance of
      repression is believed to involve propagation of heritable chromatin structures.

PMID- 19838069
TI  - SOS1 and halophytism.
AB  - Much is already known about the function and functioning of the three genes that
      make up the SOS (Salt-Overly-Sensitive) pathway in plants, but recent studies
      indicate that the linkage between external increases in salinity and stress
      protection provided by genes SOS1, SOS2 and SOS3 is more complex than previously
      appreciated. It has recently been shown that the engineered reduced expression of
      the sodium/proton antiporter SOS1 affected several pathways indicating a role for
      SOS1 that exceeds its known function as an antiporter. Interference with
      expression of SOS1, characterized as a sodium/proton antiporter in the halophyte
      Thellungiella salsuginea converted Thellungiella into an essentially glycophytic
      species.

PMID- 19838070
TI  - On the thermogenesis of the Titan arum (Amorphophallus titanum).
AB  - The Titan arum (Araceae) produces the largest bloom of all flowering plants. Its
      flowering period of two days is divided into a female flowering phase in the
      first night and a male flowering phase in the second night. Recently, we have
      documented thermogenesis in the spadix of the Titan arum during the female
      flowering phase. Here, we document a second thermogenic phase in which the male
      florets are heated during the male flowering phase. Obviously the two nocturnal
      thermogenic phases are linked with the two flowering periods. These observations
      now allow a more detailed understanding of the flowering behavior of the Titan
      arum.

PMID- 19838068
TI  - Genetically engineered, attenuated whole-cell vaccine approaches for malaria.
AB  - Malaria remains one of the most significant infectious diseases affecting human
      populations in developing countries. The quest for an efficacious malaria vaccine
      has been ongoing for nearly a century with limited success. The identification of
      malaria parasite antigens focused efforts on the development of subunit vaccines
      but has so far yielded only one partially efficacious vaccine candidate, RTS/S.
      The lack of high vaccine efficacy observed to date with subunit vaccine
      candidates raises doubts that the development of a single antigen or even a multi
      antigen malaria subunit vaccine is possible. Fortunately, it has been
      demonstrated in animal studies and experimental clinical studies that
      immunizations with live-attenuated sporozoite stages of the malaria parasite
      confer long lasting, sterile protection against infection, providing a benchmark
      for vaccine development. These early successful vaccinations with live-attenuated
      malaria parasites did not however, promote a developmental path forward for such
      a vaccine approach. The discovery of genetically engineered parasite strains that
      are fully attenuated during the early asymptomatic liver infection and confer
      complete sterile protection in animal malaria models support the development of a
      live attenuated sporozoite vaccine for Plasmodium falciparum and its accelerated
      safety and efficacy testing in malaria challenge models and in malaria endemic
      areas.

PMID- 19838071
TI  - ABA, porphyrins and plant TSPO-related protein.
AB  - We have shown that, unexpectedly, AtTSPO (Arabidopsis thaliana TSPO-related
      protein) is an endoplasmic reticulum and Golgi-localized membrane protein in
      plant cells.(1) This localization contrasts with that of mammalian 18-kDa
      translocator protein (at least for the mostly studied isoform, 18-kDa TSPO), a
      mitochondrial outer membrane protein (reviewed in ref. 2). Whereas the potential
      functions of 18-kDa TSPO are well documented, involved mainly in mitochondrial
      physiology,(2) and its interest as drugs target is been explored,(3) the roles of
      TSPO-related proteins in plant growth and development are yet to be specified.
      AtTSPO is expressed in dry seeds and can be induced in vegetative tissues by
      osmotic and salt stress or abscisic acid (ABA) treatment. Moreover, it was shown
      that the ABA-dependent induction is transient, and that boosting tetrapyrroles
      biosynthesis through 5-aminolevulinic acid (ALA) feeding enhanced downregulation
      of AtTSPO, suggesting an inherent post-translational regulation mechanism also
      involving ABA and likely porphyrins. We present additional evidence that ABA can
      help stabilize constitutively expressed AtTSPO and that ALA feeding to knockout
      mutant seeds, induces substantial germination delay. Here we discuss the possible
      link between ABA and tetrapyrroles in AtTSPO expression and post-translational
      regulation.

PMID- 19838077
TI  - Nuclear export of mRNA and its regulation by ubiquitylation.
AB  - The export of mRNA from nucleus to cytoplasm is a key regulatory step in the
      expression of RNA polymerase II genes in eukaryotes, and thus, a variety of human
      diseases are manifested by abnormal mRNA export. Therefore, a large number of
      studies over many years have been directed towards elucidating the regulatory
      mechanisms of mRNA export. These studies have identified several mRNA export
      associated factors and delineated their regulatory networks. Intriguingly, mRNA
      export has also been shown to be regulated by ubiquitylation, a post
      translational modification that targets proteins for degradation or transport and
      has been linked to different cellular processes such as cell cycle progression,
      DNA repair, transcription and intracellular trafficking. While the mechanisms of
      actions of ubiquitylation in different cellular processes are relatively well
      established, it is not clearly understood how mRNA export is regulated by
      ubiquitylation. Here, we highlight the recent advances of mRNA export and its
      regulation by ubiquitylation or the enzymes controlling this posttranslational
      modification.

PMID- 19838072
TI  - Transcriptional regulation of lignin biosynthesis.
AB  - Lignin is the second most abundant plant biopolymer mainly present in the
      secondary walls of tracheary elements and fibers in wood. Understanding how
      lignin is biosynthesized has long been an interest to plant biologists and will
      have a significant impact on tree biotechnology. Lignin is polymerized from
      monolignols that are synthesized through the lignin biosynthetic pathway. To make
      lignin, all the genes in the lignin biosynthetic pathway need to be coordinately
      turned on. It has been shown that a common cis-element, namely the AC element, is
      present in the majority of the lignin biosynthetic genes and required for their
      expression in lignifying cells. Important progress has been made in the
      identification of transcription factors that bind to the AC elements and are
      potentially involved in the coordinated regulation of lignin biosynthesis. The
      Arabidopsis MYB58 and MYB63 as well as their poplar ortholog PtrMYB28 are
      transcriptional activators of the lignin biosynthetic pathway, whereas the
      eucalyptus EgMYB2 and pine PtMYB4 transcription factors are likely Arabidopsis
      MYB46 orthologs involved in the regulation of the entire secondary wall
      biosynthetic program. It was found that the transcriptional regulation of lignin
      biosynthesis is under the control of the same transcriptional network regulating
      the biosynthesis of other secondary wall components, including cellulose and
      xylan. The identification of transcription factors directly activating lignin
      biosynthetic genes provides unprecedented tools to potentially manipulate the
      amount of lignin in wood and other plant products based on our needs.

PMID- 19838078
TI  - Interaction of yeast eIF4G with spliceosome components: implications in pre-mRNA
      processing events.
AB  - As evidenced from mammalian cells the eukaryotic translation initiation factor
      eIF4G has a putative role in nuclear RNA metabolism. Here we investigate whether
      this role is conserved in the yeast Saccharomyces cerevisiae. Using a combination
      of in vitro and in vivo methods, we show that, similar to mammalian eIF4G, yeast
      eIF4G homologues, Tif4631p and Tif4632p, are present both in the nucleus and the
      cytoplasm. We show that both eIF4G proteins interact efficiently in vitro with
      UsnRNP components of the splicing machinery. More specifically, Tif4631p and
      Tif4632p interact efficiently with U1 snRNA in vitro. In addition, Tif4631p and
      Tif4632p associate with protein components of the splicing machinery, namely
      Snu71p and Prp11p. To further delineate these interactions, we map the regions of
      Tif4631p and Tif4632p that are important for the interaction with Prp11p and
      Snu71p and we show that addition of these regions to splicing reactions in vitro
      has a dominant inhibitory effect. The observed interactions implicate eIF4G in
      aspects of pre-mRNA processing. In support of this hypothesis, deletion of one of
      the eIF4G isoforms results in accumulation of un-spliced precursors for a number
      of endogenous genes, in vivo. In conclusion these observations are suggestive of
      the involvement of yeast eIF4G in pre-mRNA metabolism.

PMID- 19838079
TI  - Protein turnover and inclusion body formation.
AB  - In a recent study, we investigated the relationship between inclusion body (IB)
      formation and the activity of the ubiquitin-proteasome system (UPS) in a primary
      neuron model of Huntington disease. We followed individual neurons over the
      course of days and monitored the level of mutant huntingtin (htt) (which causes
      Huntington disease), IB formation, UPS function, and neuronal toxicity. The
      accumulation of UPS substrates and neuronal toxicity increased with increasing
      levels of proteasome inhibition. The UPS was more impaired in neurons that
      subsequently formed IBs than in those that did not; however, after IBs formed,
      UPS function improved. These findings suggest that IB formation is a protective
      cellular response mediated in part by increased degradation of intracellular
      protein.

PMID- 19838080
TI  - Safety and immunogenicity of a tetanus toxoid, reduced diphtheria toxoid, and
      acellular pertussis vaccine when co-administered with influenza vaccine in
      adults.
AB  - Annual vaccination with trivalent influenza vaccine (TIV), and a single dose of
      tetanus toxoid-reduced diphtheria toxoid-acellular pertussis (Tdap) vaccine, are
      both recommended for adults in the US. This study was conducted to obtain
      information on the safety and immunogenicity of co-administered TIV and a Tdap
      vaccine (Boostrix) in US adults. The immunogenicity and safety of Tdap and TIV
      was evaluated in 1,497 adult subjects 19-64 years of age, who were randomized to
      receive Tdap and TIV either concomitantly or one month apart (TIV followed by
      Tdap). Seroprotection rates for diphtheria, tetanus and influenza antigens were
      high (>or=94.1%) for both vaccine regimens, and immune responses to these
      antigens in the concomitant group were non-inferior to those observed in the
      sequential group. Although antibody concentrations for pertussis antigens were
      lower in the concomitant group than in the sequential group, concomitant
      administration was shown to be non-inferior to sequential administration with
      respect to anti-pertussis toxoid concentrations one month after Tdap vaccination.
      For filamentous haemagglutinin and pertactin, the between-group differences in
      antibody concentrations marginally exceeded pre-specified limits for defining non
      inferiority. In both groups, anti-pertussis antibody concentrations were greater
      than those observed in infants following primary DTaP vaccination, in whom
      vaccine efficacy against pertussis was demonstrated. Reporting of adverse events
      appeared to be similar between groups. The data support the conclusion that Tdap
      and TIV vaccines may be co-administered without compromising either the
      effectiveness or tolerability of either vaccine.

PMID- 19838081
TI  - Involvement of glypican-3 in the recruitment of M2-polarized tumor-associated
      macrophages in hepatocellular carcinoma.
AB  - Previously, we demonstrated that membrane expression of glypican-3 (GPC3)
      stimulates the recruitment of macrophages into human hepatocellular carcinoma
      (HCC) tissues. However, functional polarization of the macrophages and the
      chemoattractant factors related to the recruitment has yet to be determined. In
      this study, to clarify the polarization (M1 or M2) of the macrophages and provide
      a clue as to the factors involved in the recruitment, we used xenograft models of
      SK-HEP-1 and SK03 cell lines with undetectable and high-level membrane expression
      of GPC3, respectively and analyzed the expression profiles of the relevant genes
      in both xenografts mainly using microarray techniques. Clustering analyses with
      mouse genome arrays revealed that the SK-HEP-1 and SK03 xenografts showed
      different expression profiles for M2 macrophage-related genes but not for M1
      macrophage-related genes. Many of the M2 macrophage-related genes were
      upregulated in the SK03 xenografts compared to the SK-HEP-1 xenografts.
      Additionally, most of the macrophages infiltrating into the SK03 xenografts were
      positive for M2 macrophage-specific markers. Regarding the chemoattractant
      factors, the microarray and quantitative real-time PCR analyses revealed that, of
      the genes reportedly related to macrophage recruitment, CCL5, CCL3 and CSF1 were
      significantly upregulated in the SK03 xenograft. These findings suggest that the
      macrophages recruited into GPC3-overexpressing (with membrane expression) HCC are
      M2-polarized ones and, more specifically, M2 tumor-associated macrophages which
      are known to promote tumor progression and metastasis, and CCL5, CCL3 and CSF1
      are possible candidate genes for the recruitment of macrophages.

PMID- 19838082
TI  - PI3K signaling in lymphocyte migration.
AB  - Lymphocyte migration is crucial for immunological surveillance. A better
      understanding of the mechanisms that regulate lymphocyte migration will help
      appreciate how lymphocytes deliver specific functions to appropriate anatomical
      sites. Phosphoinositide-3 kinases (PI3Ks) are lipid kinases that regulate
      numerous cellular responses, including cell motility and chemotaxis. Here we
      discuss how PI3K isoforms differentially regulate lymphocyte migration and
      trafficking, with an emphasis on natural killer cells.

PMID- 19838083
TI  - RNAi-mediated inhibition of Raf-1 leads to decreased angiogenesis  and tumor
      growth in gastric cancer.
AB  - This article has been retracted at the request of the Editor-in-Chief. Reason:
      The Editors have determined that the article is a duplication of the authors'
      article in Cancer Biology & Therapy (2005) 4:113-117. This is in violation of the
      journal's policy against dual publication. For more information on this policy
      see: www.landesbioscience.com/journals/cbt/guidelines/#plagiarism.

PMID- 19838084
TI  - [Crimean-Congo haemorrhagic fever: an enemy at the gates].
AB  - Crimea-Congo haemorrhagic fever is a tick-borne viral zoonosis with the potential
      of human-to-human transmission. The disease occurs in extensive areas in Asia,
      South-eastern Europe and Africa. Haemorrhagic manifestations constitute a
      prominent symptom of the late disease stage, with case fatality rates from 9 to
      50%. The recent increase in the number of cases in Eastern Europe and the
      potential for nosocomial outbreaks indicate the advisability of diagnosis in
      every patient hospitalized in Italy with haemorrhagic fever.

PMID- 19838085
TI  - Combined Diagnostic Tool for joint prosthesis infections.
AB  - While diagnosing infection of a joint prosthesis often requires a multi-modal
      approach, evaluation of combined multiple diagnostics is still a rather
      subjective process. Based on the known sensitivity and specificity of commonly
      performed tests for joint prosthesis infection, we developed the Combined
      Diagnostic Tool, a software program that automatically allows the Combined Tests
      Index (CTI) to be calculated. The CTI indicates, in a given subject, the relative
      probability of a combined series of positive tests being true compared to
      negative tests. CTI values above 1 indicate a progressively higher chance of a
      prosthesis being infected and vice versa. Double-blind, prospective evaluation of
      CTI, compared to intra-operative cultural and histological findings, was
      performed in a consecutive cohort of 36 patients. 21 patients had positive intra
      operative findings for infection. All of them had a pre-operative CTI >1 (range:
      8.8 to 5552.6; mean: 711 +/- 1298). 15 patients had negative intra-operative
      results. All had a CTI <1 (range: 0.00013 - 0.297; mean 0.074 +/- 0.099). The
      difference in CTI between the two groups was statistically significant (p =
      0.04). Our results show that the Combined Tests Index may be a useful indicator
      for differential diagnosis of prosthetic infection.

PMID- 19838086
TI  - [Efficacy and safety of TAM-sparing antiretroviral regimens in naive HIV-positive
      patients].
AB  - To assess the potency, efficacy and toxicity of abacavir/lamivudine (ABC/3TC)
      versus tenfovir/emcitrabine (TDF/FTC) with efavirenz (EFV) in naive patients with
      HIV infection a prospective observational study was carried out to evaluate
      immunovirological parameters every three months and metabolic parameters every
      six months. In all, 21 patients were enrolled (10 on ABC/3TC and 11 on TDF/FTC).
      Fisher's test revealed no statistically significant difference between the two
      arms in terms of immunological recovery and control of viral replication. For
      metabolic parameters at week 48 no statistically significant differences were
      noted between the two arms. The two ABC/3TC and TDF/FTC backbones showed the same
      potency; ABC had a more negative impact on metabolic parameters without
      statistical power.

PMID- 19838087
TI  - [Infective endocarditis: review of 36 cases].
AB  - In a retrospective study of cases of infective endocarditis (IE) observed in
      adult patients, the data of patients hospitalized for definite IE in the
      Cardiosurgery Unit of ARNAS-Civico in Palermo (Italy) from March 2003 to
      September 2006 were analysed. All cases were classified according to the modified
      Duke criteria. In all, 36 immunocompetent patients with "definite" IE were
      included (20 males and 16 females with a median age of 54 years). The aortic
      valve (23/36, 64%) was the most commonly involved, followed by the mitral (19/36,
      52.7%) and tricuspid valve (4/36, 11%). In 10 patients (27.7%), a double
      localization was observed. Blood culture yielded a positive result in 15 cases.
      Staphylococci and enterococci were the pathogens most commonly identified.
      Valvular diseases and previous cardiosurgical procedures were the risk factors
      most commonly noted. Four patients developed complications during the course of
      the disease, one of whom died. In patients with positive blood culture,
      antibiotics were prescribed on the basis of susceptibility test results. In
      patients with negative blood culture, empiric therapy was directed against Gram+
      bacteria (glycopeptides, aminoglycosides and betalactams). Surgical therapy was
      necessary in 25 patients (69.4%). The patients were subsequently enrolled in a
      cardiological and infectivological follow-up. Our results showed that rapid
      diagnosis, correct antibiotic therapy and early surgical treatment improve the
      outcome in patients with infective endocarditis.

PMID- 19838088
TI  - [Epidemiology of ESBL-positive Enterobacteriaceae in Mantova hospital (Italy)].
AB  - In a retrospective study concerning the epidemiology of extended-spectrum beta
      lactamase (ESBL) positive Enterobacteriaceae during 2007-2008 in the wards of the
      Carlo Poma hospital in Mantova, Mercurio surveillance software was used to detect
      alert microorganisms. Our objective was to link the epidemiological data with the
      type of patient and ward, and to assess the risk factors for such infections in
      particular nosocomial environments. The study enabled the change in the relative
      epidemiological data to be detected, and showed that such bacteria can be found
      almost throughout the hospital.

PMID- 19838089
TI  - [Cervical lymphoadenopathy due to Pseudomonas aeruginosa following mesotherapy].
AB  - Mesotherapy is a treatment method devised for controlling several diseases by
      means of subcutaneous microinjections given at or around the affected areas at
      short time intervals. It is used to treat a variety of medical conditions,
      amongst which all orthopaedic diseases and rheumatic pain. Mesotherapy is
      especially indicated for neck pain. The mechanism of action is twofold: a
      pharmacological effect due to the drug administered, and a reflexogenic effect,
      the skin containing many nerve endings that are sensitive to the mechanical
      action of the needle. Although this therapy is safe, like any other medical
      intervention it cannot be considered free of complications that may occur, such
      as allergies, haematomas, bruising, wheals, granulomas and telangiectasias.
      Infective complications are also possible, due to pathogenic bacteria that are
      inoculated through contamination of products, of the materials used for the
      procedure or even from germs on the skin. We present the case of a patient who
      had cervical lymphadenopathy due to Pseudomonas aeruginosa after mesotherapy
      treatment for neck pain.

PMID- 19838090
TI  - [Use of PCR for TB bacteria on BAL in early diagnosis of tubercular lobitis].
AB  - In June 2008 a 23-year-old immunocompetent came to our observation, without fever
      and with an occasional cough for 2 months, who showed two chest X-rays and a CT,
      performed respectively 60, 40 and 20 days earlier, that pointed to a small
      lobitis at the right lung base. The patient had already undergone several
      antibiotic therapies that had not changed the X-graphic framework. On
      presentation, routine blood tests and cultural examinations of sputum were
      carried out to detect common germs, fungi and TB bacteria (microscopic
      observation, cultivation and PCR), and a new antibiotic therapy
      (piperacillin/tazobactam) was started. Since the radiological picture appeared
      unchanged after 10 days of therapy and the examinations (microscopic observation
      and PCR) were negative, bronchoscopy with bacteriological evaluation of BAL was
      performed, which was positive to Mycobacterium tuberculosis, and then tubercular
      lobitis was diagnosed. Therefore a specific therapy - rifampin (RMP), isoniazid
      (INH), etambutol (EMB), pyrazinamid (PZA) - was started and changed after 10 days
      due to the growth of mycobacteria resistant to INH and EMB on examination of
      sputum. Consequently, the early use of PCR on BAL allows, in skilled hands, small
      aspecific lobitis to be diagnosed more rapidly than using cultural examination of
      sputum.

PMID- 19838091
TI  - [Immunorecovery after prolonged HIV-related immunosuppression: opportunities of
      the new antiretroviral classes].
AB  - Treatment of multi-drug experienced patients is an important concern in the
      management of HIV-1 disease, partially solved by the availability of new drugs
      acting at different phases of viral replication. Immune recovery during cART is
      linked both to the activity of antiviral drugs, as well as to the regenerative
      capability of thymus and bone marrow. We report a patient with a 22-year-old HIV
      1 disease and an AIDS diagnosis for 15 years, with extensive resistance to all
      antiretroviral drugs, who never had treatment interruption, except for short
      spells due to adverse effects. This decision was supported by both findings
      elsewhere that interruptions of cART in experienced patients with advanced
      disease are strongly associated with more rapid disease progression and by our
      evaluation of his bone marrow activity. The colony-forming cells assay performed
      in the patient showed residual clonogenic capability, increased in vitro by
      addition of protease inhibitors and IL-2. A new therapeutic scheme including
      darunavir and maraviroc allowed dramatic changes leading both to a quick
      reduction in plasmatic viral load with an impressive immune reconstitution and an
      improvement in clinical conditions.

PMID- 19838092
TI  - Aeromonas hydrophila ecthyma gangrenosum without bacteraemia in a diabetic man:
      the first case report in Italy.
AB  - Ecthyma gangrenosum is a well recognized cutaneous manifestation of severe,
      invasive infection by Pseudomonas aeruginosa usually in immunocompromised and
      critically ill patients. This type of infection is usually fatal. Aeromonas
      infection is infrequently reported as the cause of ecthyma gangrenosum. Here we
      show the first case described in Italy of Aeromonas hydrophila ecthyma
      gangrenosum in the lower extremities in an immunocompetent diabetic without
      bacteraemia. A 63-year-old obese diabetic male was admitted with an ulcer on his
      left leg, oedema, pain and fever. Throughout his hospitalization blood cultures
      remained sterile, but a culture of A. hydrophila was isolated following punctures
      from typical leg pseudomonal-ecthyma gangrenosum lesions developed after
      admission. The patient, questioned again, stated that a few days before he had
      worked in a well near his house without taking precautions. We conclude that
      early diagnosis and suitable antibiotic therapy are important for the management
      of ecthyma gangrenosum. The typical presentation of soft tissue infection of A.
      hydrophila should mimic a Gram-positive infection, which may result in a delay in
      administration of appropriate antibiotics. Moreover, A. hydrophila should be
      considered a possible agent for non-pseudomonal ecthyma gangrenosum in a diabetic
      man with negative blood cultures, in presence of anamnestical risk factors.

PMID- 19838093
TI  - [Malaria and memory in the Veneto region of Italy].
AB  - Malaria and emigration are two terms deeply embedded in Veneto history, related
      to images far back in the past, unknown to younger generations. Losing one's own
      collective historical memory is a source of personal and cultural impoverishment
      and inevitably compromises one's awareness of the present, possibly leading to
      superficial judgements and hastily formed opinions. Such a situation is all the
      more serious in a geographical area, north-eastern Italy, where immigration is so
      abundant. In this paper the authors seek to retrieve, at least in part, this
      memory, especially in terms of history (to what extent malaria afflicted
      residents in Veneto and migrants from the region) and biology (how much
      imprinting from malaria has remained in the native population's genetic make-up).

PMID- 19838094
TI  - [Evolution in the antibiotic susceptibility and resistance].
AB  - Over the last decade the proliferation of antibiotic-resistant pathogens has been
      a growing problem, especially in some geographic areas, making useless most of
      the classical antibiotic therapies. The rapid emergence of resistant bacteria is
      the result of different factors as the intrinsic microbial complexity, the
      growing attitude to travel of humans, animals and goods, the use of antibiotics
      outside hospitals, and the lack of precise therapeutic chooses for high risk
      group of patients. The antibiotic-resistance becomes certainly a serious problem
      when a resistant pathogen, and often multi-resistant today, is present in an
      infective site. In fact in a recent estimate of the Centre for Disease Control
      and Prevention (CDC) about 90.000 deaths per year in the USA are attributable to
      bacterial infections and in particular to resistant pathogens. It appears clear
      that the clinic relevance of this problem is the decimation of the sensible germs
      of the normal flora that leads to the upper hand of the only resistant bacteria.
      The antibiotic therapy, in fact, select the resistance and each bacteria has
      developed a particular strategy to survive: mutations of the genetic content or
      acquisition of resistance genes from the external. Among the Gram positive
      bacteria, besides methicillin resistant Staphyloccocus aureus, there are other
      pathogens such as coagulase-negative staphylococci (CoNS), Enterococcus faecium
      and Enterococcus faecalis, some species of streptococci and multiresistant
      Corynebacterium. The CoNS, eg. S. epidermidis, S. hominis and S. haemolyticus,
      are recognized as new important nosocomial pathogens and are not only responsible
      of invasive infections but have become in few years resistant to oxacillin (more
      than 60%) and multiresistant. The unsuspected fragility of glycopeptides, which
      for 40 years have been the most important treatment against infections due to
      Gram-positive bacteria, has posed the need for new antimicrobial molecules. Among
      the therapeutic possible options there are linezolid, tygecyline and daptomycin,
      but new other molecules are appearing in the clinical use like ceftobiprole and
      dalbavancin.

PMID- 19838095
TI  - [Treatment of multiresistant Gram positive endocarditis].
AB  - Epidemiology of infectious endocarditis has changed in last decades, endocarditis
      associated to hospital practices, sustained by multiresistant pathogens being
      highly increased. In particular, methicillin-resistant staphylococci (MRSA),
      almost resistant to a number of other antimicrobial classes, often exhibit a
      reduced susceptibility to vancomycin (h-VISA) with MICs' values more e than 1
      mg/l, leading to suppose a reduced therapeutic efficacy of this drug. Thirty-one
      percent of MRSA strains in the ICE study, which prospectively collected more than
      5000 endocarditis, were h-VISA. Daptomycin shows a rapid bactericidal activity
      against both methicillin-susceptible staphylococcci (MSSA) and MRSA, included
      those strains with reduced susceptibility to vancomycin. Daptomycin shows a good
      therapeutic efficacy in staphylococcal endocarditis: MRSA 71%, MSSA 75%. These
      data suggest the use of daptomycin as initial therapy for treatment of
      staphylococcal endocarditis, independently from methcillin susceptibility. Some
      experimental data showed that daptomycin efficacy can diminish, if it is used as
      a rescue therapy after vancomycin failure. The thickness of bacterial cell-wall
      recognized in h-VISA strains can represent a physical and electrical barrier to
      reach both the vancomycin and daptomycin target site. However, the reduced
      efficacy of daptomycin following vancomycin exposure is an extremely rare event
      in the clinical practice. It is preferrable to use daptomycin as first line
      therapy, at a proper dosage. As far as endocarditis is concerned, recent data
      proved the excellent daptomycin tolerability, with dosages up to 8-10 mg/kg/die.
      During the treatment, CPK values must be always monitored. For endocarditis
      sustained by vancomycin-resistant enterococci, therapeutic choices are based on
      linezolid or ampicillin-ceftriaxone combination therapy. Daptomycin alone, or in
      association with gentamycin and rifampin, can represent a promising therapeutic
      alternative.

PMID- 19838096
TI  - [Infections in the immunocompromised host: role of daptomycin].
AB  - Infections in immunocompromised host are increasing worldwide. Definition of
      immunocompromised host encompasses a number of different pathologies, such as
      immune-haematological, oncological, intensivist, in addition to all patients
      being treated with different monoclonal antibodies and TNF-alfa inhibitors.
      Daptomycin is a novel lipopeptide antimicrobial drug, its activity against Gram
      positive bacteria being rapidly cidal, without phenomenon related to bacterial
      lysis. Daptmomycin received approval for treatment of complicated skin and skin
      structures infections, sepsis, and right side endocarditis sustained by S.
      aureus. This article will focus the role of this new drug in the treatment of
      severe infections in the immunocompromised host. Clinical cases observed recently
      will be also presented.

PMID- 19838097
TI  - HAART during pregnancy and during breastfeeding among HIV-infected women in the
      developing world: has the time come?

PMID- 19838098
TI  - Rosuvastatin versus pravastatin in dyslipidemic HIV-1-infected patients receiving
      protease inhibitors: a randomized trial.
AB  - BACKGROUND: HIV infection and its treatment with protease inhibitors, especially
      when boosted with ritonavir, can cause lipid disorders. Statins, with the
      exception of fluvastatin, pravastatin and rosuvastatin, interact with protease
      inhibitor metabolism via CYP450. Pravastatin is recommended for patients with
      protease inhibitor-associated dyslipidemia. Rosuvastatin is the statin most
      effective on low-density lipoprotein cholesterol (LDL-c) in non-HIV patients.
      METHODS: HIV-1-infected patients treated with boosted protease inhibitor were
      randomized to receive either rosuvastatin 10 mg/day or pravastatin 40 mg/day for
      dyslipidemia (LDL-c >4.1 mmol/l and triglycerides <8.8 mmol/l). The percentage
      change in LDL-c, triglyceride and high-density lipoprotein-cholesterol levels,
      measured in a central laboratory, was determined after 45 days of statin
      treatment. RESULTS: Eighty-eight patients were randomized and 83 took the study
      drugs, 41 rosuvastatin and 42 pravastatin. The median duration of prior
      antiretroviral treatment was 9 years. At baseline, the median LDL-c level was
      4.93 mmol/l, the triglyceride level 2.29 mmol/l, and the high-density lipoprotein
      cholesterol level 1.27 mmol/l. The median percentage changes in the rosuvastatin
      and pravastatin arms were -37 and -19% for LDL-c (P < 0.001), respectively, and 
      19 and -7% for triglycerides (P = 0.035), respectively. The change in the high
      density lipoprotein-cholesterol level was not significantly different between the
      two arms. None of the four severe adverse events was attributed to the statins;
      in particular, there were no renal, hepatic or muscular events. CONCLUSION:
      Rosuvastatin 10 mg/day was more effective than pravastatin 40 mg/day on LDL-c and
      triglyceride levels in HIV-1-infected patients receiving a boosted protease
      inhibitor.

PMID- 19838099
TI  - Dasatinib-induced pleural effusions: a lymphatic network disorder?
AB  - Dasatanib, which has been approved for rescue therapy for patients with imatinib
      resistant chronic myelogenous leukemia and Philadelphia chromosome positive acute
      lymphoblastic leukemia, is a novel, orally available multitargeted kinase
      inhibitor of BCR-ABL and SRC family kinases (Quintas-Cardama et al, J Clin Oncol
      2007;25:3908-14). It binds to both active and inactive conformations of the ABL
      gene and is 325 times more potent than imatinib in inhibiting the growth of
      BCR/ABL cells in vitro (Morelock and Sahn, Chest 1999;116:212-21; Huggins and
      Sahn, Clin Chest Med 2004;25:141-53). Although dasatinib is a generally well
      tolerated drug in the treatment of Philadelphia chromosome positive hematopoetic
      malignancies, pleural effusions have been frequently noted and have been reported
      in up to 35% of patients (Sahn SA. Drug-induced pleural disease. In: Camus P,
      Rosenow E, editors. Drug-induced iatrogenic lung disease. London: Hodder Arnold;
      2009). Although there have been numerous reports of effusions, none have provided
      complete pleural fluid analysis; therefore, we report 2 patients with dasatinib
      induced pleural effusion with complete pleural fluid analysis.

PMID- 19838100
TI  - Self-reported influences of hopelessness, health literacy, lifestyle action, and
      patient inertia on blood pressure control in a hypertensive emergency department
      population.
AB  - BACKGROUND: In response to almost universally recorded poor blood pressure (BP)
      control rates, we developed a novel health paradigm model to examine the mindset
      behind BP control barriers. This approach, termed patient inertia (PtInert), is
      defined as an individual's failure to take responsibility for health conditions
      and proactive change. METHODS: PtInert was evaluated through a survey instrument
      conducted in 85 subjects with a prior history of hypertension seen in an
      emergency department. The survey tool encompassed the Wide Range Achievement Test
      4, the brief symptom inventory, and a PtInert questionnaire. RESULTS: Fifty
      percent of patients reported slight psychological distress (psychosomatic >
      anxiety > depression), with 61% possessing hopelessness surrounding complications
      from high BP no matter their actions. An unanticipated finding was that patients
      who had a low reading proficiency (83.1 + 16.4 Wide Range Achievement Test 4
      standard score) self-reported high levels of hypertension health literacy. Less
      than half of patients transferred this health literacy into lifestyle changes in
      diet, exercise, and medication adherence. Although patients felt that they could
      control their BP and frequently thought about better BP control, 55% of the
      subjects had uncontrolled hypertension (>140/90 mm Hg). CONCLUSION: Hypertensive
      patients visiting our emergency department perceive themselves to have adequate
      hypertension health-related literacy that was not transferred into hypertension
      health protective behavioral practices. Psychological distress and a sense of
      hopelessness surrounding BP control contribute to the lack of protective
      behavioral health practices. Further evaluations of PtInert methods to promote
      successful proactive change and adherence warrant further study.

PMID- 19838101
TI  - Assessing diabetes-related knowledge among internal medicine residents using
      multiple-choice questionnaire.
AB  - BACKGROUND: To design a comprehensive tool to assess the knowledge of
      pathophysiology, diagnosis, treatment, and care of patients with diabetes
      mellitus among medical students (MS) and residents and to evaluate this tool in a
      hospital setting. METHODS: A multiple-choice questionnaire with 21 questions was
      designed and administered to MS and residents. Cronbach alpha test was used to
      assess the internal consistency of the questionnaire, and chi2 analysis was used
      to test statistically significant difference among different groups. RESULTS: A
      total of 4 groups of MS, 15 postgraduate year 1 (PGY1), 8 PGY2, 4 PGY3, and 3
      PGY4 participated in the study. The survey showed a good overall internal
      consistency (Cronbach alpha = 0.5). The percent of correct responses for MS,
      PGY1, PGY2, PGY3, and PGY4 were 75 +/- 4.2%, 79.8 +/- 13.5%, 81.5 +/- 16.1%, 85.6
      +/- 12.3%, and 88.4 +/- 12.8%, respectively. CONCLUSIONS: We successfully
      designed and administered a diabetes knowledge assessment tool. This novel tool
      can be used in different settings to assess knowledge about important components
      of diabetes care among housestaff and steer practice-based learning. We observed
      trends toward improving level of knowledge with increase in the duration of
      training.

PMID- 19838103
TI  - Mortality after elective abdominal aortic aneurysm repair.
AB  - OBJECTIVE: Purpose of this study is to provide detailed age- and gender-specific
      mortality risks of patients hospitalized for elective AAA repair. SUMMARY
      BACKGROUND DATA: Whether to perform elective abdominal aortic aneurysm (AAA)
      surgery is balancing the risks of natural history against the risks of surgical
      intervention. Literature is lacking mortality risks after elective AAA repair
      with stratification by both age and gender. METHODS: Mortality risks for 28 days,
      1 year, and 5 years were derived from a nationwide cohort of patients
      hospitalized for elective AAA repair in 1997 or 2000. This cohort was formed
      through linkage of the Hospital Discharge Register with the Dutch Population
      Register. The relations between demographics, medical history and mortality were
      studied by Cox regression. RESULTS: A total of 3457 patients were identified; 86%
      males, mean age 72 +/- 8.0 years. Mortality risks after elective AAA repair
      increased with age: 28-day mortality ranged from 3.3% to 27.1% in men and 3.8% to
      54.3% in women, 5-year mortality from 12.9% to 78.1% in men and 24.3% to 91.3% in
      women. Higher age, congestive heart failure, cerebrovascular disease and diabetes
      mellitus were independent risk factors for 5-years mortality. CONCLUSIONS:
      Mortality risks after elective AAA repair are strongly age-related. Age, gender,
      and comorbidities should be taken into account when deciding on surgery. A
      general threshold of 55 mm for surgery might not be justified for all patients.

PMID- 19838104
TI  - Terror explosive injuries: a comparison of children, adolescents, and adults.
AB  - OBJECTIVE: We sought to characterize injuries and outcomes from terror explosions
      with specific attention to children (0-10 years) and adolescents (11-15 years)
      compared to adults (16-45 years). SUMMARY BACKGROUND DATA: Terror explosions
      target vulnerable populations and result in multidimensional injuries that may
      vary according to age group. The relative dearth of information regarding terror
      related injuries among children inhibits proper preparedness and optimum
      management during such an event. METHODS: A retrospective study was performed
      using data from the national Israel Trauma Registry (October 2000 to December
      2005). Included were civilians and nonactive military personnel hospitalized as a
      result of a terror explosion. RESULTS: During the 5.3-year study period, 49
      children (0-10 years), 65 adolescents (11-15 years), and 723 adults (16-45 years)
      were hospitalized from terror explosions. Children were more likely than adults
      to sustain severe injuries (27% vs. 12%) and traumatic brain injury (35% vs. 20%)
      and less likely to sustain injuries to their extremities (35% vs. 57%) or open
      wounds (39% vs. 59%) (P <or= 0.05). The adolescent injury profile was similar to
      that of adults, however, adolescents presented with less internal injuries, more
      contusions, and superficial wounds to extremities and were more likely to require
      surgery for mild to moderate wounds. Differences in hospital utilization and
      outcomes by age groups were observed when data were stratified by injury
      severity. CONCLUSIONS: Compared to adults, children, and adolescents exposed to
      terror explosions present with different injuries and hospital utilization and
      outcomes. These results further confirm that preparedness of a pediatric
      healthcare system is essential for effective management in the event of a future
      mass casualty incident.

PMID- 19838105
TI  - Morbidity and mortality outcomes of cytoreductive surgery and perioperative
      intraperitoneal chemotherapy at a single tertiary institution: towards a new
      perspective of this treatment.
AB  - INTRODUCTION: Cytoreductive surgery (CRS) combined with perioperative
      intraperitoneal chemotherapy (PIC) is a treatment option for peritoneal surface
      malignancy. Despite the survival benefits, this treatment was previously
      associated with a high morbidity and mortality rates and the perception of the
      poor perioperative outcomes associated with this regimen remains. The aim of this
      study was to report the perioperative outcomes of CRS and PIC from a single
      institution to review factors that are associated with a poor perioperative
      outcome. METHODS: The clinical- and treatment-related data of 243 consecutive
      procedures performed were prospectively collected and retrospectively reviewed.
      Adverse events were rated according to the National Cancer Institute's Common
      Toxicity Criteria (grade I-V). Univariate and multivariate analyses were
      performed to identify significant clinical and treatment-related factors for a
      poor perioperative outcome (grades III/IV/V morbidity). RESULTS: The
      perioperative mortality rate was 3%. The rate of severe morbidity was 43%.
      Multivariate analysis demonstrated that left upper quadrant peritonectomy (P <
      0.001) and small bowel resection (P < 0.01) were factors that predicted for a
      poor perioperative outcome. CONCLUSIONS: The morbidity and mortality rates of CRS
      and PIC are within an acceptable range for a major gastrointestinal surgery which
      is performed with a curative intent. Patient selection is important in ensuring
      that suitable patients receive this treatment. A new perspective of this
      treatment needs to be sought.

PMID- 19838106
TI  - Anatomical segmental and subsegmental resection of the liver for hepatocellular
      carcinoma: a new approach by means of ultrasound-guided vessel compression.
AB  - BACKGROUND: Anatomic resection is considered the gold standard approach for liver
      resection in patients with hepatocellular carcinoma. The use of intraoperative
      ultrasound (IOUS) as guidance is indispensable in this sense but methods
      available up to now were rather complex and for that reason of limited use. We
      herein describe a novel technique for the demarcation of the resection area by
      means of IOUS-guided finger compression to systematically accomplish anatomic
      segmental and subsegmental resections. METHODS: Thirty-three patients met the
      eligibility criteria. This technique consisted in the demarcation of the
      resection area by IOUS-guided finger compression of the vascular pedicle feeding
      the tumor at the level closest to the tumor but oncologically suitable. Median
      age was 65 years (range, 36-81). There were 25 men and 8 women. Median tumor
      number was 1 (range, 1-2); median tumor size was 2 cm (range, 1-10). Twenty-five
      (76%) patients had cirrhosis or chronic hepatitis, and 8 (24%) had steatosis
      (ClinicalTrials.Gov ID: NCT00829335). RESULTS: Procedure resulted feasible in all
      eligible patients, and demarcation area was obtained in all patients within 1
      minute of bimanual IOUS-guided compression. There was no mortality or major
      morbidity: only 7 (21%) patients experienced minor morbidity. No blood
      transfusions were administered. CONCLUSIONS: Systematic segmentectomy and
      subsegmentectomy by IOUS-guided finger compression is a feasible, safe, and
      effective technique, which could be considered as a simpler alternative to those
      up to now proposed.

PMID- 19838107
TI  - Major cancer surgery in the elderly: results from the American College of
      Surgeons National Surgical Quality Improvement Program.
AB  - OBJECTIVE: To examine the association between older age and short-term outcomes
      after major oncologic resections. SUMMARY BACKGROUND DATA: The effect of older
      age on outcomes from major cancer surgery remains conflicting because of
      limitations in measuring coexisting comorbidities. Given the critical role of
      surgery, older patients and their surgeons often question decisions regarding
      major cancer surgery. METHODS: We identified 8781 patients who underwent elective
      or emergent major thoracic, abdominal, or pelvic resections for neoplasms in the
      2005 to 2007 American College of Surgeons National Surgical Quality Improvement
      Program database. Pre, intra-, and postoperative characteristics were compared by
      age groups. Multivariable techniques were used to predict adjusted short-term
      operative outcomes. RESULTS: Older patients were more likely to have preoperative
      comorbidities and to receive intraoperative blood transfusions, but at the same
      time have shorter operative times. Increased age was also associated with higher
      operative mortality (4.83% for >or=75 years vs. 1.09% for ages 40-55 years), a
      greater frequency of major complications, and more prolonged hospital stays-all
      of which persisted after multivariable adjustments. Despite its strong
      association with 30-day operative mortality, the impact of older age was
      comparable to other preoperative risk-factors predictive of short-term operative
      outcomes. CONCLUSIONS: The present study, which is one of the largest
      multihospital studies, showed that older age is independently associated with
      worse short-term outcomes after major oncologic resections. However, the effect
      of age was not prohibitively worse, and is comparable to the effects of other
      preoperative risk factors. These findings support the use of risk-based treatment
      decision-making in older patients.

PMID- 19838108
TI  - Association analysis of the IL-17F His161Arg polymorphism in myocardial
      infarction.
AB  - BACKGROUND: There is growing evidence that coronary atherosclerosis and its most
      severe phenotype, myocardial infarction (MI), are chronic inflammatory diseases.
      Interleukins are important mediators and modulators of inflammation. The
      His161Arg polymorphism in the gene encoding of IL-17F has recently been
      consistently found to be associated with chronic inflammatory disorders. In this
      study, we explored the hypothesis that the variant also affects the risk of MI.
      METHODS: We conducted a case-control association study on a cohort of 513
      unrelated MI patients and 477 age-matched and sex-matched controls in a Chinese
      Han population. RESULTS: Differences in the genotype distributions and allele
      frequencies of this polymorphism between cases and controls were insignificant (P
      = 0.38 and 0.57, respectively). Further stratification for age, sex, the number
      of diseased coronary arteries, and other cardiovascular risk factors did not
      affect the negative findings. CONCLUSION: This study indicates for the first time
      that, unlike other chronic inflammatory diseases, the IL-17F His161Arg
      polymorphism is unlikely to be a major contributor to the pathogenesis of MI.

PMID- 19838109
TI  - Heart rate variability and heart rate recovery in patients with coronary artery
      ectasia.
AB  - BACKGROUND: Coronary artery ectasia (CAE) is characterized by an abnormal
      dilatation of the coronary arteries, which is a variant of coronary artery
      disease (CAD). Increased sympathetic activity or decreased vagal modulation of
      cardiac function assessed by heart rate variability (HRV) analysis has been
      associated with an increased risk of coronary artery disease and mortality and
      angiographic progression of coronary atherosclerosis, as well as arrhythmia and
      sudden cardiac death. Heart rate recovery index is a strong indicator of risk in
      asymptomatic and symptomatic CAD. To the best of our knowledge, no study has been
      conducted to investigate the relationship between HRV, heart rate recovery, and
      CAE. The purpose of this study was to examine the changes in heart rate recovery
      and HRV measurements in coronary artery ectasia. METHODS: The study population
      consisted of 50 consecutive patients (24 women; mean age 46+/-5 years) with CAE,
      and 35 asymptomatic healthy individuals comprised the control group (19 women;
      mean age 44+/-7 years). We performed electrocardiography, echocardiography,
      Holter analysis, exercise stress test, routine biochemical tests and evaluated
      the clinical characteristics. Time-domain parameters of HRV (mean R-R intervals;
      standard deviations of all N-N intervals; standard deviations of the averages of
      N-N intervals), the root mean square of the difference in successive R-R
      intervals, proportion derived by dividing the number of interval differences of
      successive N-N intervals greater than 50 ms by the total number of N-N intervals
      (pNN50) were evaluated. Heart rate recovery was defined as the difference in the
      heart rate from peak exercise to 1 min after peak exercise. RESULTS: Standard
      deviations of all N-N intervals (123.7+/-30.3 vs. 178.8+/-52.7, P<0.001),
      standard deviations of the averages of N-N intervals (95.2+/-27.1 vs. 120.2+/
      39.6, P = 0.001), total number of N-N intervals (11.9+/-8.6 vs. 17.1+/-6.4, P =
      0.004) were significantly lower in the CAE group than in healthy controls. The
      root mean square of the difference in successive R-R intervals was lower in CAE
      patients than controls, but the differences between groups were not statistically
      significant (47.5+/-23.1 vs. 56.2+/-23.6, P = 0.097). The heart rate recovery
      values measured during the recovery phase were significantly lower in the CAE
      group compared with the control group (21.3+/-11.1 vs. 29.3+/-11.9, P = 0.002).
      The incidence of abnormal heart rate recovery [22 (44%) vs. 5 (14%), P = 0.002]
      was greater in patients with CAE group than in controls. CONCLUSION: The results
      of this study showed that time-domain HRV parameters and heart rate recovery were
      reduced in patients with CAE.

PMID- 19838110
TI  - Relation between N-terminal pro-B-type natriuretic peptide and coronary plaque
      components in patients with acute coronary syndrome: virtual histology
      intravascular ultrasound analysis.
AB  - BACKGROUND: The N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a
      sensitive indicator of hemodynamic stress and its increased level is associated
      with higher mortality in acute coronary syndrome (ACS) patients. Virtual
      histology-intravascular ultrasound (VH-IVUS) can provide quantitative information
      on plaque components. METHODS: We measured preprocedural serum NT-pro-BNP levels
      in 156 ACS patients with preserved left ventricular systolic function and normal
      serum creatinine. VH-IVUS classified the color-coded tissue into four major
      components: fibrotic, fibro-fatty, dense calcium, and necrotic core (NC). Thin
      cap fibroatheroma (TCFA) was defined as focal, NC-rich (>or=10% of the cross
      sectional area) plaques being in contact with the lumen in a plaque burden of at
      least 40%. We divided the patients into two groups according to the NT-pro-BNP
      levels [group I: >or=200 pg/ml (n = 58) vs. group II: <200 pg/ml (n = 98)].
      RESULTS: The percent areas of NC at the minimum lumen site (19.8+/-13.1% vs.
      15.2+/-11.1%, P = 0.027) and at the largest NC site (24.7+/-10.3% vs. 19.2+/
      11.4%, P = 0.015) were significantly greater in group I than in group II. Percent
      NC volume was significantly greater in group I than in group II (15.8+/-8.1% vs.
      10.1+/-9.1%, P = 0.008). The total number of TCFAs was 38 in group I and 56 in
      group II. The presence of at least one TCFA (58 vs. 38%, P = 0.009) and multiple
      TCFAs (25 vs. 10%, P = 0.005) within culprit lesions were observed more
      frequently in group I than in group II. The TCFAs were located more in proximal
      in group I than in group II [the length from coronary ostium to TCFA: 10.8+/-7.6
      mm in group I vs. 25.7+/-16.3 mm in group II (P<0.001)]: 85% of TCFAs was located
      within 20 mm from coronary ostium in group I; conversely only 36% of TCFAs was
      located within 20 mm from coronary ostium in group II (P<0.001). CONCLUSION: VH
      IVUS analysis shows that ACS patients with high NT-pro-BNP levels had more
      vulnerable plaque component (more NC-containing lesions and higher frequency of
      culprit lesion TCFAs) and had more proximally located TCFAs.

PMID- 19838111
TI  - Recurrent second trimester pregnancy loss: evaluation and management.
AB  - PURPOSE OF REVIEW: Recurrent pregnancy loss usually refers to first trimester
      losses. The present article describes the importance of a thorough evaluation for
      any patient presenting with a second trimester loss, and reviews current data
      regarding evidence-based evaluation and management for those families who have
      had recurrent episodes of second trimester losses. A management protocol is
      presented to guide management of a current pregnancy with a history of recurrent
      second trimester losses. RECENT FINDINGS: Previous literature has focused on
      isolated causes of second trimester loss and management. The present review
      incorporates all presentations of loss into a stepwise evaluative and management
      paradigm. SUMMARY: This comprehensive literature review and management protocol
      will provide the clinician with a thorough, systematic, and practical approach to
      the patient with recurrent pregnancy loss in order to maximize her chance of
      optimal pregnancy outcome.

PMID- 19838112
TI  - The role of assisted reproductive technology in the management of recurrent
      pregnancy loss.
AB  - PURPOSE OF REVIEW: Description of genetic screening of preimplantation embryos as
      a means of reducing miscarriages in patients with recurrent pregnancy loss.
      RECENT FINDINGS: That the promise of preimplantation genetic screening (PGS) for
      ameliorating recurrent pregnancy loss has been fulfilled is controversial. An
      array of comparative studies has suggested a positive effect of PGS on
      implantation rate, but these have been balanced by studies showing no effect or a
      negative effect, highlighting the need for more rigorously designed studies and
      randomized controlled trials. Emerging technologies may provide more information
      from the embryo biopsies even as the mosaicism of the embryo and its implications
      for interpreting PGS data are recognized. SUMMARY: Through the screening of
      embryos for abnormality in chromosome number or structure and selecting only
      normal embryos for transfer, PGS was envisioned and applied as a therapeutic tool
      for improving implantation and live birth rates from in-vitro fertilization and
      providing a means of attenuating pregnancy loss in recurrent pregnancy loss
      patients. An array of reports on the effects of PGS on embryo implantation and
      live birth rates has been made since its introduction, showing, variously,
      increases, decreases or no changes in these parameters. Various factors may
      influence the efficacy of PGS, including the patient population to which it is
      applied, technical aspects such as embryo biopsy, the genetic analysis and embryo
      culture environment, the current limitation of the genetic analysis (a subset of,
      rather than all, the 24 chromosomes) and the mosaicism of the embryo and
      blastocyst. Collectively, these contribute to the challenge of optimizing PGS and
      understanding how the screening result reflects the ultimate genetic constitution
      of the conceptus. Emerging cytogenetic and molecular technologies such as
      comparative genomic hybridization and microarray analysis may provide a broader
      appraisal of the embryo for a more comprehensive evaluation of developmental
      potential and prognosis for live birth.

PMID- 19838114
TI  - Mesenchymal stem cell interactions with growth factors on kidney repair.
AB  - PURPOSE OF REVIEW: To review the current knowledge of the contribution of
      mesenchymal stem cells (MSCs) during renal repair and the factors and mechanisms
      underlying these effects. RECENT FINDINGS: Although many studies using MSCs as
      therapeutic agents have been published in recent years, our understanding is
      incomplete how migration, growth, and differentiation of adult MSCs are governed
      by interactions with resident renal cells, growth factors, and cytokines.
      Different laboratories have shown that extrarenal stem cells contribute to renal
      regeneration: MSCs migrate into injured renal tissue, are integrated into the
      tubular system, and differentiate into epithelial cells. Nevertheless, a couple
      of studies could not verify these results in all, but despite this they have
      shown a beneficial effect of administered MSCs on renal regeneration. It is well
      established that renal tubular epithelial cells secrete growth factors and
      cytokines. These factors participate in renal repair as paracrine regulators or
      chemoattractants to induce migration of extrarenal stem cells, whereas only
      limited data are available about the interactions between all key players during
      renal repair mechanisms. SUMMARY: Although different studies demonstrate the
      effectiveness of MSC therapy, there are still open questions defining the
      mechanism of action during homing and differentiation and the long-term safety on
      the way to a therapeutic option.

PMID- 19838115
TI  - Angiopoietins: vascular growth factors looking for roles in glomeruli.
AB  - PURPOSE OF REVIEW: The present review highlights general advances concerning
      angiopoietin (Ang) biology and then focuses on possible roles of these molecules
      within healthy and diseased glomeruli. RECENT FINDINGS: Early experiments showed
      that Ang1 stabilizes newly formed vessels and reduces vascular permeability, with
      Ang2 blocking Ang1 activation of the Tie2 receptor. Recent studies found that
      Ang2 can directly stimulate Tie2 and that both Ang1 and Ang2 can be pro
      inflammatory. Ang/Tie2 biology is modified by vascular endothelial growth factor
      and by a related receptor, Tie1. In health, Tie1 and Tie2 are expressed by
      glomerular endothelia, whereas podocytes express Ang1. In-vitro studies show that
      exogenous Ang1 enhances capillary formation within developing glomeruli. Ang1
      applied to glomerular endothelial monolayers increases transcellular electrical
      resistance and reduces albumin transit, effects associated with enhanced cell
      surface glycocalyx. Glomerular Ang2 expression increases in diabetic
      glomerulopathy and immune-mediated glomerulonephritis. When glomerular Ang2 is
      experimentally upregulated in healthy mice, endothelial apoptosis and albuminuria
      increase, and vascular endothelial growth factor and nephrin are downregulated.
      SUMMARY: Experimental evidence does not yet exist to allow us to assign
      definitive in-vivo glomerular functions to the angiopoietins. Key experiments
      will be to study the effects of downregulating Ang1 in healthy animals and
      downregulating Ang2 levels in glomerular disease.

PMID- 19838116
TI  - Using evoked compound action potentials to assess activation of electrodes and
      predict C-levels in the Tempo+ cochlear implant speech processor.
AB  - OBJECTIVE: In this study, we analyze how electrically evoked compound action
      potential (ECAP) responses can be used to assess whether electrodes should be
      activated in the map and to estimate C levels in the Med-El Tempo+ Cochlear
      Implant Speech Processor. DESIGN: ECAP thresholds were measured using the ECAP
      Recording System of the Pulsar CI implant. Twenty-one postlingually and 28
      prelingually deafened patients participated in this study. The relationship
      between ECAP responses and the activation of electrodes was analyzed. Because an
      error in the estimation of T levels (behavioral thresholds) has less effect on
      hearing quality than an error in the estimation of C levels in the Tempo+
      cochlear implant speech processor (maximum comfort levels), correlation and
      regression analyses were performed between ECAP thresholds and C levels. RESULTS:
      The observation of an evoked potential generally implied that the electrode was
      activated because only 3.5% of electrodes that yielded measurable evoked
      responses were deactivated, because of collateral stimulations or an unpleasant
      hearing sensation. In contrast, the absence of an evoked potential did not imply
      that an electrode should be deactivated, because 20% of these electrodes provided
      a useful auditory sensation. ECAP responses did not predict the absolute
      behavioral comfort levels because of the excessive error between behavioral C
      levels and those derived from ECAP thresholds (the mean relative error is
      43.78%). However, by applying a normalization procedure, ECAP measurements
      allowed the C-level profile to be predicted with a mean relative error of 6%;
      that is, they provided useful data to determine the C level of each electrode
      relative to the average C level of the patient. CONCLUSIONS: ECAP is a reliable
      and an useful objective measurement that can assist in the fitting of the Tempo+
      cochlear implant speech processor. From results presented in this work, a
      protocol is proposed for fitting this cochlear implant system. This protocol
      facilitates appropriate cochlear implant fitting, particularly for children or
      uncooperative patients.

PMID- 19838113
TI  - Susceptibility genes in common complex kidney disease.
AB  - PURPOSE OF REVIEW: This paper reviews recent efforts to identify genetic variants
      conferring risk for chronic kidney disease. A brief overview of methods for
      identifying gene variants is provided, along with genetic associations and new
      avenues under exploration. RECENT FINDINGS: The role of renal failure
      susceptibility genes, including MYH9, ELMO1, UMOD and ACTN4, has become clearer
      over the past 18 months. The spectrum of MYH9-associated kidney disease,
      including focal segmental glomerulosclerosis, global glomerulosclerosis and
      collapsing glomerulopathy, related entities contributing to approximately 43% of
      end-stage renal disease in African-Americans, has come to light. SUMMARY: MYH9
      will re-categorize focal segmental glomerulosclerosis and related disorders, and
      has clarified the relationship between hypertension and kidney disease. MYH9
      polymorphisms account for much of the excess risk of HIV-associated nephropathy
      and nondiabetic kidney disease in African-Americans. Kidney disease associations
      with ELMO1 and UMOD have been replicated and applications of genome-wide
      association studies based on expression data are providing novel insights on
      renal protein expression. These breakthroughs will alter our approach to kidney
      disease surveillance and lead to new therapeutic options.

PMID- 19838117
TI  - Predicting auditory nerve survival using the compound action potential.
AB  - OBJECTIVE: Advances in cochlear hair-cell regeneration, neural regeneration, and
      genetic therapy encourage continued development of diagnostic tests that can
      accurately specify the appropriate target within the cochlea and auditory nerve
      for delivery of therapeutic agents. In this study, we test the hypothesis that
      the morphology of the acoustically evoked compound action potential (CAP) may
      reflect the condition of the auditory nerve in individuals with sensorineural
      hearing loss. DESIGN: CAPs to tone burst stimuli at octave frequencies from 1 to
      16 kHz were recorded at low- to high-stimulus levels from sedated Mongolian
      gerbils with partial lesions of the auditory nerve (n = 10). Distortion-product
      otoacoustic emissions were measured to ensure preservation of normal outer hair
      cell function. CAPs were analyzed with conventional measures of N1 latency and
      amplitude and by fitting the CAPs with a mathematical model that includes a
      parameter (N) representing the number of nerve fibers contributing to the CAP and
      a parameter (f) representing the oscillation frequency of the CAP waveform. Nerve
      fiber density and percent normal nerve area were estimated from cross-sections of
      the auditory nerve bundle. RESULTS: Despite substantial lesions in the auditory
      nerve, CAP thresholds remained within normal or were only moderately elevated and
      were not correlated with histological measures of nerve fiber density and normal
      nerve area. At high-stimulus levels, the model parameter N was strongly
      correlated with nerve fiber density for three of the five test frequencies and
      with normal nerve area for all five test frequencies. Correlations between N1
      amplitude measures at high-stimulus levels and our histological measures were
      also significant for the majority of test frequencies, but they were generally
      weaker than the correlations for the model parameter N. The model parameter f, at
      low- and high-stimulus levels, was also positively correlated with measures of
      normal nerve area. CONCLUSIONS: Consistent with previous findings, physiological
      measures of threshold were not correlated with partial lesions of the auditory
      nerve. The model parameter N at high-stimulus levels was strongly correlated with
      normal nerve area suggesting, that it is a good predictor of auditory nerve
      survival. The model parameter N also seemed to be a better predictor of the
      condition of the auditory nerve than the conventional measure of N1 amplitude.
      Because the model parameter f was correlated with normal nerve area at low- and
      high-stimulus levels, it may provide information on the functional status of the
      auditory nerve.

PMID- 19838119
TI  - Additional value of SPIO-enhanced MR imaging for the noninvasive imaging
      diagnosis of hepatocellular carcinoma in cirrhotic liver.
AB  - OBJECTIVES: The purpose of this study is to determine whether adding
      superparamagnetic iron oxide (SPIO)-enhanced MR images to the 2 dynamic imaging
      modalities, triphasic CT scan and dynamic MR imaging (MRI), improves the
      diagnosis of hepatocellular carcinomas (HCCs) compared with the noninvasive
      diagnosis provided by the European Society of Study of the Liver (EASL) criteria.
      MATERIALS AND METHODS: This retrospective study included 108 patients with 152
      histologically confirmed hepatocellular nodules, ie, 28 dysplastic nodules and
      124 HCCs. Of the 124 HCCs, 79 were larger than 2 cm in diameter, 34 were between
      1 to 2 cm, and 11 were less than 1 cm. The reviewers retrospectively analyzed by
      consensus the hypervascularity of the nodules on both dynamic CT and MR images as
      well as their signal intensity on SPIO-enhanced images. Sensitivity, specificity,
      and diagnostic accuracy were assessed based on the EASL noninvasive diagnostic
      criteria for HCC and SPIO-combined EASL criteria. RESULTS: Seventeen (14%) of 124
      HCCs were hypovascular HCC according to both imaging modalities, and hypovascular
      HCC was more frequently seen in the subgroup of HCC < or = 2 cm in diameter. A
      significant improvement in the sensitivity (78% to 96%) for diagnosing HCCs
      larger than 2 cm in diameter, was achieved by adding SPIO-enhanced MR images to 2
      dynamic studies compared with the noninvasive diagnosis according to the EASL
      criteria (P < 0.01). When the EASL criteria were applied to the 34 HCCs of 1 to 2
      cm in diameter, 21 lesions (62%) were correctly diagnosed using the EASL criteria
      and 29 lesions (85%) according to the SPIO-combined EASL criteria. CONCLUSIONS:
      Adding SPIO-enhanced MR images to the dynamic imaging modalities, including
      triphasic CT and dynamic MRI, improves the noninvasive diagnosis of HCCs compared
      with using only the EASL criteria, especially when attempting to diagnose
      hypovascular or slightly hypervascular HCCs. As these images combine information
      regarding the function or deficit of Kupffer cells within the hepatic nodules
      with vascularity information, combining sequentially acquired SPIO-enhanced MRI
      with dynamic MRI could be considered to be the single-step imaging modality with
      a high degree of accuracy in the diagnostic work-up of small HCCs.

PMID- 19838118
TI  - A decline in walking distance predicts long-term outcome in patients with known
      or suspected peripheral artery disease.
AB  - AIM: To assess the predictive value of a decline in total walking distance and
      ankle brachial index (ABI) on all-cause mortality and cardiac death in patients
      with known or suspected peripheral artery disease. METHODS: Two hundred and sixty
      one patients, who performed single-stage treadmill walking test twice to evaluate
      their peripheral artery disease, were enrolled in an observational study.
      Patients who underwent surgery during follow-up were excluded. Delta total
      walking distance and delta resting and exercise ABI consisted of the difference
      between the first and the second test. All three variables were categorized into
      two groups: stable/improvement or a decline. RESULTS: The mean follow-up period
      was 6 years. At both 5 years and total follow-up, a decline in total walking
      distance was independent and highly associated with an increased mortality risk
      and cardiac death [hazard ratio: 2.31 (95% confidence interval 1.35-3.96); hazard
      ratio: 3.55 (95% confidence interval: 1.53-8.21), respectively]. A decline in
      resting or exercise ABI after adjustment for delta walking distance was not
      significantly associated with all-cause mortality or cardiac death. CONCLUSION: A
      decline in total walking distance in single-stage treadmill exercise tests is a
      strong prognostic predictor of all-cause mortality and cardiac death in the short
      term and long term.

PMID- 19838120
TI  - Increased ablation zones using a cryo-based internally cooled bipolar RF
      applicator in ex vivo bovine liver.
AB  - PURPOSE: To evaluate the feasibility of ex vivo ablation implementing a cryo
      based internally cooled bipolar radiofrequency (RF) applicator and to determine
      the influence of power and gas pressure on the size and shape of the resulting
      ablation zones. MATERIALS AND METHODS: Two hundred twenty-five ablations were
      performed using a custom-built internally CO2-cooled bipolar cryo RF applicator
      in ex vivo bovine livers. The active tip of the applicator was 55 mm long. RF
      power (32-50 watts) and gas pressure of cooling medium (500-600 psi) were varied
      independently. Power was applied in continuous mode. Control group experiments
      were carried out solely using the RF function at 32, 40, and 50 watts. Ablation
      duration was 15 minutes for all applications. Experiments were repeated 5 times
      for all parameter combinations. Short and long axes of the induced white ablation
      zone were macroscopically assessed. The ablation zone was referred to as
      homogeneous if complete ablation was observed without spots of untreated tissue.
      The short axis diameters for the simultaneous application of cryo and RF function
      were analyzed using a multiple linear regression analysis. An unpaired Mann
      Whitney U test was used to analyze the differences between the short axes with RF
      alone and RF using cryo cooling. RESULTS: All ablation zones were homogeneous.
      Using simultaneous RF ablation function and gas cooling with a single applicator,
      the long axes of the ablation zones ranged between 42 +/- 2 mm (mean +/- SD) and
      59 +/- 5 mm, the short axes between 24 +/- 1 and 44 +/- 1 mm, depending on the
      parameter combination. At a stable gas pressure level, short axes increased with
      rising power levels and decreased after reaching a maximum. The maxima of the
      short axis increased with higher gas pressure levels and were shifted to higher
      power values. Optimal parameter settings were 46 to 50 watts and 600 psi gas
      pressure, resulting in a short axis of 44 +/- 1 mm. Short axis weakly correlated
      with gas pressure (r2 = 0.10) and power (r2 = 0.34) alone, whereas the
      correlation was r2 = 0.76 for the combined factors. Without cooling, short axis
      diameters were significantly shorter (P < 0.05), ranging between 13 +/- 2 mm at
      50 watts and 15 +/- 2 mm at 32 watts. CONCLUSION: The results of this initial ex
      vivo study show that the combined cryo RF ablation device allows for large
      ablation volumes using a single needle, which is superior to RF ablation alone.

PMID- 19838121
TI  - Differentiation of pancreas carcinoma from healthy pancreatic tissue using
      multiple b-values: comparison of apparent diffusion coefficient and intravoxel
      incoherent motion derived parameters.
AB  - OBJECTIVES: To evaluate in detail the diagnostic performance of diffusion
      weighted imaging (DWI) to differentiate pancreas carcinoma from healthy pancreas
      using the apparent diffusion coefficient (ADC) and parameters derived from the
      intravoxel incoherent motion (IVIM) theory. MATERIALS AND METHODS: Twenty-three
      patients with pancreas carcinoma and 14 volunteers with healthy pancreas were
      examined at 1.5 Tesla using a single-shot echo-planar imaging DWI pulse sequence.
      Eleven b-values ranging from 0 to 800 s/mm2 were used. The acquisition was
      separated into blocks (b0, b25), (b0, b50),...(b0, b800) and each block was
      acquired in a single expirational breath-hold (TA = 26 seconds) to avoid motion
      artifacts. The ADC was calculated for all b-values using linear regression
      yielding ADC(tot). By applying the IVIM model, which allows for the estimation of
      perfusion effects in DWI, the perfusion fraction f and the perfusion free
      diffusion parameter D were calculated. The diagnostic performance of ADC, f and D
      as a measure for the differentiation between healthy pancreas and pancreatic
      carcinoma was evaluated with receiver operating characteristics analysis.
      RESULTS: In the healthy control group, the ADC(tot) ranged from 1.53 to 2.01
      microm2/ms with a mean value of 1.71 +/- 0.19 microm2/ms, the perfusion fraction
      f ranged from 18.5% to 40.4% with a mean value of 25.0 +/- 6.2%, and the
      diffusion coefficient D from 0.94 to 1.28 microm2/ms with a mean value of 1.13 +/
      0.15 microm2/ms. In patients with pancreas carcinoma, the ADC(tot) ranged from
      0.98 to 1.81 microm2/ms with a mean value of 1.31 +/- 0.24 microm2/ms, the
      perfusion fraction f ranged from 0% to 20.4% with a mean value of 8.59 +/- 4.6%
      and the diffusion coefficient D from 0.74 to 1.60 microm2/ms with a mean value of
      1.15 +/- 0.22 microm2/ms. In comparison to healthy pancreatic tissue, a
      significant reduction of the perfusion fraction f and of ADC(tot) was found in
      pancreatic carcinoma (P < 0.00001, 0.0002, respectively). The f value showed more
      than a 10-fold higher significance level in distinguishing cancerous from normal
      tissue when compared with the ADC(tot) value. No significant difference in the
      diffusion coefficient D was observed between the 2 groups (P > 0.5). In the
      receiver operating characteristic-analyses, the area under curve for f was 0.991
      and significantly larger than ADC(tot) (P < 0.05). f had the highest sensitivity,
      specificity, negative predictive value, and positive predictive value with 95.7%,
      100%, 93.3%, and 100%, respectively. CONCLUSIONS: Using the IVIM-approach, the f
      value proved to be the best parameter for the differentiation between healthy
      pancreas and pancreatic cancer. The acquisition of several b-values strongly
      improved the stability of the parameter estimation thus increasing the
      sensitivity and specificity to 95.7% and 100% respectively. The proposed method
      may hold great promise for the non invasive, noncontrast-enhanced imaging of
      pancreas lesions and may eventually become a screening tool for pancreatic
      cancer.

PMID- 19838122
TI  - Feasibility of functional cardiac MR imaging in mice using a clinical 3 Tesla
      whole body scanner.
AB  - OBJECTIVES: To test the feasibility of cardiac MR imaging in mice using a
      clinical 3 Tesla whole body MR system for structural and functional analysis.
      Standard protocols for bright blood cine imaging were adapted for murine
      dimensions. To validate measurements of functional parameters the MR data were
      compared with high-resolution echocardiographic measurements. MATERIALS AND
      METHODS: Cardiac imaging was carried out in CD 1 wild-type mice (n = 8). MR
      imaging studies were performed using a clinical 3 Tesla MR system (Achieva,
      Philips). All mice received 2 MR scans and 1 echocardiographic evaluation. For
      optimal MR signal detection a dedicated solenoid receive-only coil was used.
      Electrocardiogram signal was recorded using a dedicated small animal
      electrocardiogram monitoring unit. For imaging we used a retrospectively
      triggered TFE sequence with a repetition time of 12 ms and an echo time of 4 ms.
      A dedicated software patch allowed for triggering of cardiac frequency of up to
      600 BPM. Doppler-echocardiography was performed using a VisualSonics Vevo 770
      high-resolution imaging system with a 30 MHz scanhead. Axial/lateral resolution
      was 40 of 100 microm and temporal resolution was 150 to 300 frames/s (B-mode) and
      1000 frames/s (M-mode) depending on the setting. RESULTS: MR imaging was
      successfully carried out in all mice with a sufficient temporal resolution and
      good signal-to-noise ratio and contrast-to-noise ratio levels allowing for
      identification of all relevant structures. Accordingly, there was a good scan
      rescan reproducibility of MR measurements: Interassay coefficients of variance
      ranged from 4% for ejection fraction to 12% for endsystolic volume (ESV).
      Magnetic resonance imaging and echocardiography gave comparable results when
      using the same geometric model (Teichholz method): EDV: 60.2 +/- 6.1 microL/59.1
      +/- 12.3 microL, ESV: 20.0 +/- 2.6 microL/20.7 +/- 7.7 microL, EF: 66.7% +/-
      4.0%/65.2% +/- 9.9%, CO 19.5 +/- 3.6 mL/17.9 +/- 2.9 mL. Bland-Altman analysis
      gave acceptable limits of agreement between both methods: EDV (+28.2/-26.1), ESV
      (+16.3/-17.7), EF (+19.0/-16.1), CO (10.7/-7.5). When applying the Simpson's
      method MR volume estimates were significantly higher compared with
      echocardiography resulting in a lower estimate for the ejection fraction (60% +/-
      3.9% vs. 66.7% +/- 4.0%). CONCLUSIONS: Cardiac MR imaging of mice using a
      clinical 3 Tesla MR system for functional analysis is feasible with sufficient
      spatial and temporal resolution, good repeatability and reliable results when
      compared with high-resolution echocardiography.

PMID- 19838123
TI  - Infection with different hiv subtypes is associated with CD4 activation
      associated dysfunction and apoptosis.
AB  - Determination of HIV-1 subtype may be important in the management of HIV-infected
      individuals, particularly with regard to deciding the CD4 cell count at which to
      initiate antiretroviral therapy. Non-B subtypes, A and D, are prevalent in
      Uganda, and individuals infected with subtype D seem to have faster disease
      progression compared with those infected with subtype A. We examined the level of
      apoptosis in CD4+ T cells in a study cohort of volunteers infected with subtypes
      A and D infection. Although the levels of apoptosis in the activated CD4+ cells
      significantly decreased with viral suppression, CD4+ apoptosis in individuals
      infected with subtype D were found to be significantly higher compared with those
      infected with subtype A before antiretroviral treatment. Surface expression of PD
      1 on CD4 cells in subtype D was substantially higher compared with that in
      subtype A (P = 0.03). This difference was not observed in the CD8 population (P >
      0.05). Our findings suggest that the infecting HIV subtypes exert an independent
      influence on the disease outcome in response to antiretroviral treatment.

PMID- 19838124
TI  - Undiagnosed HIV prevalence among adults and adolescents in the United States at
      the end of 2006.
AB  - OBJECTIVES: To describe adults/adolescents (age 13 years and older) living with
      undiagnosed HIV infection in the United States at the end of 2006. METHODS: HIV
      prevalence and percentage undiagnosed were estimated from cumulative HIV
      incidence using an extended back-calculation model (using both HIV and AIDS data,
      the time of first diagnosis with HIV, and disease severity at diagnosis) and
      estimated cumulative deaths. RESULTS: An estimated 1,106,400 adults/adolescents
      (95% confidence interval = 1,056,400-1,156,400) were living with HIV in the
      United States at the end of 2006; overall, 21.0% (232,700; 95% confidence
      interval = 221,200-244,200) were undiagnosed. Whites had the lowest percentage
      undiagnosed (18.8%) compared with Hispanics/Latinos (21.6%), blacks/African
      Americans (22.2%), American Indians/Alaska Natives (25.8%), and Asians/Pacific
      Islanders (29.5%; all P < 0.001). Persons with a behavioral risk of injection
      drug use (IDU) had the lowest percentage undiagnosed (female IDU: 13.7% and male
      IDU: 14.5%); men exposed through heterosexual contact had the highest (26.7%)
      followed by men who have sex with men (23.5%). CONCLUSIONS: Differences in
      undiagnosed HIV were evident across demographic and behavior groups. Effective
      testing programs and early access to treatment and prevention services are
      necessary to reduce undiagnosed HIV infections and HIV prevalence.

PMID- 19838125
TI  - Prior therapy influences the efficacy of lamivudine monotherapy in patients with
      lamivudine-resistant HIV-1 infection.
AB  - BACKGROUND: The M184V mutation decreases the replication capacity of HIV-1. This
      prospective study aimed to characterize the virologic and immunologic changes
      during monotherapy with lamivudine (3TC) in patients with limited options for a
      fully suppressive new therapy. METHODS: Clinically stable patients with CD4 cells
      greater than 300/microL, previous virologic failure, and a M184V mutation were
      treated with 3TC 300 mg once daily during 48 weeks. The primary study endpoint
      was time to CD4 cell decrease by 30% or to below 200 cells/microL. RESULTS:
      Patients were switched from either a protease inhibitor (PI)-containing highly
      active antiretroviral therapy (PI group, N = 10) or from reverse transcriptase
      (RT) inhibitor regimens (RT group, N = 16). Among all 26 patients with a median
      baseline HIV-1 RNA of 3866 copies/mL and CD4 cell count of 432/microL, the
      probability of reaching the endpoint after 12, 24, 36, and 48 weeks was 15%, 36%,
      57%, and 70%, respectively. The median time to the endpoint was 6.0 months. In
      the PI versus the RT group, 81% versus 40% reached the CD4 endpoint (P < 0.05);
      the CD4 decline was -170 versus -99 cells/microL (P < 0.05). The replication
      capacity of the RT increased from mean 53% to 73% (P < 0.01). The increase in the
      replication capacity of the protease was greater in the PI group (from 51% to
      72%, P = 0.07) than in the RT group (from 70% to 82%, P = 0.32). Mutations
      detected at baseline reverted partially to the wild type. No new HIV-associated
      illnesses and no 3TC-related toxicities were reported during the study.
      CONCLUSIONS: 3TC monotherapy as a partial treatment interruption did not prevent
      immunologic deterioration in the majority of patients. It may be considered a
      temporary maintenance strategy in selected patients failing under RT inhibitors
      only. Withdrawal of the residual activity of a PI from the failing regimen led to
      a faster CD4 decline, possibly because of greater increase in the fitness of the
      protease gene.

PMID- 19838127
TI  - Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive
      patients.
AB  - OBJECTIVE: To better characterize the long-term effects of tenofovir on renal
      function in a large managed care organization. METHODS: We performed a
      retrospective cohort analysis in Kaiser Permanente for years 2002 to 2005
      comparing renal function among antiretroviral naive patients initiating a
      tenofovir-containing regimen (964 patients) or tenofovir-sparing regimens (683
      patients). We evaluated glomerular filtration rate (GFR, [Modification of Diet in
      Renal Disease equation]), serum creatinine, and the development of renal proximal
      tubular dysfunction. We report multivariable hazard ratios (HR, Cox modeling) and
      linear outcomes (repeated measures) with predictors retained if P < 0.10
      (backward selection). Potential predictor variables included in multivariate
      models were age, sex, Black race, baseline laboratories (including CD4 count),
      history of diabetes mellitus, hypertension, malignancy, hepatitis, and concurrent
      medications. RESULTS: Overall, tenofovir-exposed patients had a larger relative
      decline in GFR through 104 weeks (-7.6 mL/min/1.73 m(2) relative to tenofovir
      sparing, P < 0.001); the degree of the difference varied by baseline GFR, with
      the greatest effect seen in those patients with GFR greater than 80 mL/min/1.73
      m(2). Tenofovir-exposed patients had greater development of proximal tubular
      dysfunction over time (at 52 wk: HR(adjusted) = 1.95 [P = 0.01] and at 104 wk:
      HR(adjusted) = 5.23 [P = 0.0004]) and had greater risk of medication
      discontinuation (HR(adjusted) = 1.21, P = 0.02), especially as renal function
      worsened. Viral control and CD4 count changes were similar between the two
      groups. CONCLUSIONS: Tenofovir is associated with greater effect on decline in
      renal function and a higher risk of proximal tubular dysfunction in
      antiretroviral naive patients initiating antiretroviral therapy.

PMID- 19838128
TI  - High rates of survival, immune reconstitution, and virologic suppression on
      second-line antiretroviral therapy in South Africa.
AB  - To determine rates of survival, viral suppression, and immunologic change after 1
      year on second-line antiretroviral therapy, we conducted a cohort study among 328
      patients initiated on zidovudine, didanosine, and lopinavir/ritonavir. All
      patients who switched to standard second-line therapy at a large urban public
      sector clinic in Johannesburg, South Africa, were included. A year after
      initiating second-line therapy 243/313 [78%; 95% confidence interval (CI) 73%
      82%], subjects were alive and in care. Further, 203/262 (77%; 95% CI: 72%-82%)
      had a suppressed viral load by 1 year. Mean CD4 gain by 12 months was 133
      cells/microL (95% CI: 106-160). Patients on second-line therapy had a small
      decreased likelihood of being alive and in care by 1 year [hazard ratio (HR)
      0.84; 95% CI: 0.73-0.97] as time-matched comparisons on first-line antiretroviral
      therapy (ART). Patients switched before 2 viral loads >1000 (HR 1.68; 95% CI:
      1.08-2.61), and those switched for reasons not related to noncompliance with
      first-line (HR 1.83; 95% CI: 1.14-2.93) were more likely to achieve virologic
      suppression by 1 year on second-line ART. As rates of treatment failure over the
      first year on second-line therapy were low, provision of second-line treatment to
      patients who fail their first-line ART should be considered a high priority in
      resource-poor settings.

PMID- 19838129
TI  - Pregnancy, contraceptive use, and HIV acquisition in HPTN 039: relevance for HIV
      prevention trials among African women.
AB  - BACKGROUND: Biomedical HIV prevention trials enroll sexually active women at risk
      of HIV and often discontinue study product during pregnancy. We assessed risk
      factors for pregnancy and HIV acquisition, and the effect of pregnancy on time
      off study drug in HIV Prevention Trials Network 039. METHODS: A total of 1358 HIV
      negative, herpes simplex virus type 2-seropositive women from South Africa,
      Zambia, and Zimbabwe were enrolled and followed for up to 18 months. RESULTS: A
      total of 228 pregnancies occurred; time off study drug due to pregnancy accounted
      for 4% of woman-years of follow-up among women. Being pregnant was not associated
      with increased HIV risk (hazard ratio 0.64, 95% confidence interval 0.23-1.80, P
      = 0.40). However, younger age was associated with increased risk for both
      pregnancy and HIV. There was no association between condom use as a sole
      contraceptive and reduced pregnancy incidence; hormonal contraception was not
      associated with increased HIV risk. Bacterial vaginosis at study entry was
      associated with increased HIV risk (hazard ratio 2.03, P = 0.02). CONCLUSIONS:
      Pregnancy resulted in only a small amount of woman-time off study drug. Young
      women are at high risk for HIV and are an appropriate population for HIV
      prevention trials but also have higher risk of pregnancy. Condom use was not
      associated with reduced incidence of pregnancy.

PMID- 19838130
TI  - Short-term administration of the CCR5 antagonist vicriviroc to patients with HIV
      and HCV coinfection is safe and tolerable.
AB  - OBJECTIVE: CCR5 antagonists block HIV cell entry through competitive binding to
      the CCR5 receptor present on the surface of CD4(+) cells. The CCR5 receptor is
      also present on CD8(+) cells involved in clearing hepatitis C virus (HCV). The
      goal of the present study was to examine the short-term safety of a CCR5
      antagonist, vicriviroc, in patients with HIV/HCV coinfection. METHODS: A
      randomized, double-blind trial was conducted in 28 HIV/HCV-coinfected subjects
      with compensated liver disease and plasma HIV RNA below 400 copies/mL. All
      subjects were receiving a ritonavir-enhanced protease inhibitor regimen, to which
      vicriviroc (5, 10, or 15 mg/day) or placebo was added for 28 days. Clinical and
      laboratory evaluations were performed 21 days beyond the treatment period.
      RESULTS: Treatment with vicriviroc resulted in no clinically meaningful changes
      in HCV or HIV viral load or any immune parameters. Adverse events were equally
      distributed among placebo and vicriviroc groups. Transaminase elevations of grade
      1 or more were reported as AEs in 1 subject receiving 10-mg vicriviroc and 1
      placebo subject. Vicriviroc plasma concentrations were similar to those observed
      in healthy subjects. CONCLUSIONS: Short-term treatment with vicriviroc as part of
      a ritonavir-containing protease inhibitor-based regimen was safe and well
      tolerated in HIV/HCV-coinfected subjects. HIV/HCV coinfection also did not affect
      vicriviroc pharmacokinetics.

PMID- 19838131
TI  - Reappraisal of European guidelines on hypertension management: a European Society
      of Hypertension Task Force document.

PMID- 19838132
TI  - Nitric oxide dysfunction in vascular endothelium and platelets: role in essential
      hypertension.
AB  - Both endothelial and platelet-derived nitric oxide have important
      vasculoprotective properties. Increasing evidence suggests a dysfunctional
      platelet nitric oxide synthase type 3 (NOS3) pathway in essential hypertension,
      whereas for endothelial-derived nitric oxide the picture is more complicated,
      with many studies suggesting an impairment of endothelial nitric oxide
      generation, whilst others have suggested that the endothelial nitric oxide
      pathway is preserved. Controversy also exists as to whether any observed
      reduction in endothelial or platelet-derived nitric oxide exerts a pathogenetic
      role or is simply the result of the raised blood pressure. In this review, we
      examine the evidence that endothelial and/or platelet-derived nitric oxide are
      disturbed in essential hypertension, and whether such disturbances are cause or
      effect.

PMID- 19838133
TI  - Slipped upper femoral epiphysis in a 19-year-old male.
AB  - The authors present a case of unilateral slipped upper femoral epiphysis (SUFE)
      in a 19-year old-male patient. An accompanying hypogonadism was noted on physical
      examination and laboratory tests. Extensive endocrinological work up revealed
      constitutional delay in puberty as the cause of hypogonadism. This is the first
      reported case of constitutional delay in puberty presenting with SUFE in English
      literature. There were six cases of SUFE reported in the literature at an age
      older than the typical age range (10-16 years), of which five cases were the
      result of hypopituitarism and one case of radiation-induced hypooestrogenism. Our
      case highlights the importance of thorough history taking, clinical examination
      and early involvement of the endocrinology team in SUFE presenting at an age
      older than the typical age range to prevent delay in diagnosis and appropriate
      treatment.

PMID- 19838134
TI  - You get what you pay for.

PMID- 19838135
TI  - Transplantation of Von Hippel-Lindau peptide delivered neural stem cells promotes
      recovery in the injured rat spinal cord.
AB  - For transplantation of neural stem cells (NSCs) to repair the injured spinal
      cord, neuronal differentiation of NSCs before transplantation has more
      satisfactory effect because differentiation grafted NSCs are restricted to the
      glial lineage. Therefore, we focused on the Von Hippel-Lindau protein (VHL),
      which has the potential to induce neuronal differentiation of NSCs. Here, we show
      the transplantation of protein transduction domain-linked VHL peptide-delivered
      NSCs promotes the repair of the injured spinal cord. Transplantation of protein
      transduction domain -linked VHL peptide-delivered NSCs more recovered the
      behaviors of the rats than that of nondelivered NSCs, and engrafted NSCs
      differentiated to neuronal marker positive cells. Thus, our finding of the
      neuronal differentiation through VHL-peptide transfer has the great potential to
      cure the spinal cord injury.

PMID- 19838136
TI  - 3D versus 2D dynamic 82Rb myocardial blood flow imaging in a canine model of
      stunned and infarcted myocardium.
AB  - PURPOSE: Previous studies have shown the ability of rubidium-82 ((82)Rb) positron
      emission tomography (PET) imaging to quantitatively measure myocardial blood flow
      (MBF), many of which are performed using two-dimensional (2D) imaging. Three
      dimensional (3D) imaging provides increased sensitivity and may result in
      decreased costs owing to a reduction in the required injected activity of
      radiotracer. This study compares 2D and 3D (82)Rb PET MBF results obtained in the
      same imaging session. METHODS: Three-dimensional and 2D (82)Rb perfusion imaging
      was performed in canines on a GE Discovery LS PET/CT scanner at rest and during
      hyperemia in stunned and infarcted tissue. MBF (ml/min/g) was determined using a
      1-compartment model and an extraction correction of the uptake rate and analyzed
      using a standard 17-segment model. RESULTS: A strong, significant correlation was
      present (rho = 0.95, P<0.0001). Average 3D MBF values were slightly lower at rest
      and higher during stress versus 2D. MBF results in normal, stunned, and infarcted
      tissue differed by 7% on average and significant increases in MBF from rest to
      hyperemia were noted with both the techniques. CONCLUSION: These results imply
      that MBF results obtained in 3D are comparable with traditional 2D imaging.
      Therefore, it may be possible to use 3D imaging with lower administered activity,
      helping to reduce costs and patient dose without compromising quantitative
      information.

PMID- 19838137
TI  - Steroids for early acute respiratory distress syndrome: critical appraisal of
      Meduri GU, Golden E, Freire AX, et al: Methylprednisolone infusion in early
      severe ARDS: results of a randomized controlled trial. Chest 2007; 131:954-963.

PMID- 19838138
TI  - The motor response to stimulation predicts outcome as well as the full Glasgow
      Coma Scale in children with severe head injury.
AB  - OBJECTIVES: To evaluate how well the full Glasgow Coma Scale and the motor
      response, which is a subscore of the Glasgow Coma Scale, predict the outcome in
      children who have sustained a traumatic brain injury. The best scores in the
      first 24 hrs were used. DESIGN: A retrospective observational study. SETTING: A
      pediatric intensive care unit. PATIENTS: Children admitted between January 1997
      and December 1999. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Recovery
      with independent function (good outcome), or death, persistent coma, or dependent
      (bad outcome) at 6 months after the injury. Complete information was available
      for 130 patients. Both the full Glasgow Coma Scale and the motor response
      predicted outcome well: the area under the receiver operating characteristic plot
      was 0.88 (95% confidence interval, 0.82-0.95) for the full score and 0.89 (0.82
      0.95) for the motor response. CONCLUSIONS: Both the full Glasgow Coma Scale score
      and the motor response provide a useful indication of long-term outcome, although
      neither score is sufficiently accurate to be used to limit treatment. The full
      Glasgow Coma Scale does not have a linear relationship with mortality, and there
      is poor interobserver agreement. The motor response should be used in children in
      preference to the full Glasgow Coma Scale; the predictive power is equivalent to
      the full Glasgow Coma Scale, there is a linear relationship to mortality, and it
      is easier to collect accurately.

PMID- 19838139
TI  - Reducing the incidence of necrotizing enterocolitis in neonates with hypoplastic
      left heart syndrome with the introduction of an enteral feed protocol.
AB  - OBJECTIVE: Neonates with hypoplastic left heart syndrome are prone to
      gastrointestinal complications, including necrotizing enterocolitis, during
      initiation or advancement of enteral feeds. A feeding protocol was developed to
      standardize practice across a multidisciplinary team. The purpose of this study
      was to examine the impact of a standardized feeding protocol on the incidence of
      necrotizing enterocolitis and overall postoperative gastrointestinal morbidity.
      DESIGN: Retrospective case-control study. SETTING: Cardiothoracic intensive care
      unit of a tertiary care children's hospital. PATIENTS: Ninety-eight neonates with
      hypoplastic left heart syndrome admitted to the cardiothoracic intensive care
      unit after first-stage palliation. INTERVENTION: A retrospective chart review was
      performed. Two groups were analyzed: the preprotocol group (n = 52) was examined
      from January 2000 through December 31, 2001, and the postprotocol group (n = 46)
      from February 2002 through December 31, 2003. MEASUREMENTS AND MAIN RESULTS: The
      incidence of suspected or diagnosed necrotizing enterocolitis as defined by the
      modified Bell staging criteria was recorded. Data were also collected regarding
      postoperative day of enteral feed initiation, postoperative day full feeds
      attained, and postoperative hospital length of stay. Necrotizing enterocolitis
      was detected in 14 preprotocol (27%) and three postprotocol (6.5%) patients (p <
      .01). Enteral feeds were initiated later in the postprotocol group (7.5 vs. 5.5
      days, p < .001), and number of days to full feeds was also later in the
      postprotocol group (7 vs. 4 days, p = .02). Hospital length of stay tended to be
      shorter in the postprotocol group (21.5 vs. 28 days, p = .25). CONCLUSION:
      Measures directed at reducing the incidence of necrotizing enterocolitis may
      reduce morbidity in neonates with hypoplastic left heart syndrome and reduce cost
      by decreasing hospital length of stay. A standardized feeding protocol instituted
      to address these problems likely contributed to reducing the incidence of
      necrotizing enterocolitis in this high-risk population.

PMID- 19838140
TI  - Home extubation by a pediatric critical care team: providing a compassionate
      death outside the pediatric intensive care unit.
AB  - Our objective is to present a case report of home extubation by a pediatric
      intensive care team in a terminally ill pediatric patient. Literature relevant to
      home extubation will be reviewed. The design is a case report. Home extubation of
      critically ill children may offer significant benefits and an alternative end-of
      life option for families. Allowing a child to die at home creates an opportunity
      for families to maintain privacy and to better address their spiritual and
      cultural needs at the time of death. Before offering home extubation to families,
      hospitals should prepare families for the experience and address the availability
      of staff to comfort parents and provide bereavement support. Medicolegal as well
      as cost issues for the hospital related to home extubation should be explored
      before the implementation of a program of this nature. This case illustrates that
      home extubation is a creative, compassionate, and culturally sensitive
      alternative to hospital-based end-of-life care involving the pediatric
      intensivist, transport teams, and primary care physicians.

PMID- 19838141
TI  - Change in blood-brain barrier permeability during pediatric diabetic ketoacidosis
      treatment.
AB  - OBJECTIVE: Cerebral edema is a devastating complication of pediatric diabetic
      ketoacidosis. We aimed to examine blood-brain barrier permeability during
      treatment of diabetic ketoacidosis in children. DESIGN: Prospective observational
      study. SETTING: Seattle Children's Hospital, Seattle, WA. PATIENTS: Children
      admitted with diabetic ketoacidosis (pH <7.3, HCO3 <15 mEq/L, glucose >300 mg/dL,
      and ketosis). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Subjects
      underwent two serial paired contrast-enhanced perfusion (gadolinium) and
      diffusion magnetic resonance imaging scans. Change in whole brain and regional
      blood-brain barrier permeability (permeability ratio*100 and % permeability ratio
      change) between illness and recovery were determined. Time 0 reflects start of
      insulin treatment. Thirteen children (median age 10.0 +/- 1.1 yrs; seven female)
      with diabetic ketoacidosis were enrolled. Permeability ratio increased from time
      1 (first magnetic resonance image after time 0) to time 2 (second magnetic
      resonance image after time 0) in the frontal cortex (ten of 13 subjects),
      occipital cortex (ten of 13 subjects), and basal ganglia (nine of 13). Whole
      brain permeability ratio increased from time 1 to time 2 (160%) and regional
      increase in permeability ratio was greatest in the frontal cortex (148%) compared
      with the occipital cortex (128%) and basal ganglia (112%). CONCLUSIONS: Overall,
      whole brain and regional blood-brain barrier permeability increased in most
      subjects during diabetic ketoacidosis treatment. The frontal region had more
      blood-brain barrier permeability than other brain regions examined.

PMID- 19838142
TI  - Educational preparation and postgraduate training curriculum for pediatric
      critical care nurse practitioners.
AB  - BACKGROUND: Nurse practitioners (NPs) in pediatric intensive care units have
      increased dramatically over recent years. Although state regulations are changing
      pediatric nurse practitioner certification, licensure and credentialing
      requirements, available acute care, and critical care educational programs are
      limited. Thus, entry-level practitioners continue to have varied clinical
      experience and educational preparation. OBJECTIVE: To describe the current
      educational preparation and scope of practice of pediatric NPs and provide
      guidelines for postgraduate training to successfully integrate NPs into the
      pediatric intensive care unit (PICU). DESIGN: A group of NPs practicing in
      pediatric critical care recognized the imminent need for comprehensive
      orientation guidelines that are readily accessible to physicians and other nurse
      practitioners to successfully transition entry-level NPs into the PICU. The NPs
      held many discussions to identify commonalities and differences in the education
      foundation in pediatric NP programs, expected clinical experience and knowledge
      of NP students, and anticipated needs and gaps for the entry-level practitioner.
      A convenience sample of 20 pediatric critical care nurse practitioners practicing
      for > or =5 yrs were interviewed to examine current orientation processes for
      entry-level NPs into the PICU. Sample orientation guidelines, job descriptions,
      and procedural competency forms were collected and reviewed from various PICUs
      across the United States. An orientation model was drafted and distributed to a
      secondary panel of ten experienced practitioners to gather expert opinions.
      Responses were reviewed and a revised draft of the document was distributed to a
      group of APNs involved in postgraduate education. RESULTS: A PICU orientation
      model for entry-level pediatric critical care nurse practitioners was developed.
      CONCLUSIONS: The orientation curriculum presented here may serve as a resource
      for NPs and collaborating physicians who are developing a training program for
      entry-level practitioners.

PMID- 19838144
TI  - Generic drugs revisited.

PMID- 19838143
TI  - Empiric antibiotics are justified for infants with respiratory syncytial virus
      lower respiratory tract infection presenting with respiratory failure: a
      prospective study and evidence review.
AB  - OBJECTIVE: Although some studies indicate a low risk of serious bacterial
      infection in infants with respiratory syncytial virus (RSV), these studies
      focused on patients who did not progress to respiratory failure. We hypothesized
      the composite diagnosis of concomitant bacterial pneumonia (CBP) is common in
      lower risk infants with RSV who present in respiratory failure. The aim of the
      study was to investigate the incidence of CBP in low-risk infants mechanically
      ventilated for RSV respiratory failure and to compare the results with other
      studies searched for in MEDLINE. DESIGN: Prospective, descriptive study, and
      literature review. Two MEDLINE searches were done using the terms 1) respiratory
      syncytial virus (RSV) and pneumonia, and 2) RSV, pneumonia, and antibiotics.
      SETTING: Tertiary pediatric intensive care unit (PICU) in the Northeast United
      States. PATIENTS: We prospectively enrolled 23 infants admitted to our PICU with
      RSV infection and respiratory failure over a 27-month period. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: All infants were intubated on arrival or
      soon thereafter; 22 had diagnostic tracheal aspiration performed, and 20 had
      blood cultures obtained shortly after admission. All had white blood cell count,
      temperature measured, and chest radiograph. Only one had antibiotics before
      culture. The length of mechanical ventilation, PICU course, and hospital stay
      were recorded.The primary outcome variable was the composite diagnosis of CBP as
      determined by the following criteria: 1) isolation of pathogenic bacteria from a
      tracheal aspirate, 2) blood culture, 3) chest radiograph, 4) temperature
      abnormality, and 5) peripheral white blood cell count. In our study, 7 infants
      met four criteria (probable pneumonia); 6 met three criteria (possible
      pneumonia); and 10 infants met less than three criteria. By tracheal aspirate
      criteria alone, 9 of 23 (39%) had probable pneumonia and 9 of 23 had possible
      pneumonia by previously published criteria. The mean length of mechanical
      ventilation for 7 infants who met four criteria was 10 +/- 2.7 (sem) days; for 6
      infants who met three criteria, 10.5 +/- 2.1 days; and for infants who met less
      than three criteria 7.4 +/- 0.9 days. The mean PICU stay was 14.3 +/- 3.6 days
      for infants who met four criteria; 14.3 +/- 3.0 days for infants who met three
      criteria; and 9.9 +/- 1.4 days for infants who met less than three criteria. The
      mean hospital stay was 16.3 +/- 3.4 for infants who met four criteria; 18.7 +/-
      2.8 days for infants who met three criteria; and 24.8 +/- 9.6 days for infants
      who met less than three criteria. These differences were not statistically
      significant. A MEDLINE search was performed using the terms 1) RSV and pneumonia,
      and 2) RSV, pneumonia, and antibiotics. CONCLUSIONS: While the small size of this
      study does not permit definitive conclusions, these data, in combination with
      other data from the literature, suggest that composite evidence of bacterial
      pneumonia in otherwise low-risk infants with RSV presenting with respiratory
      failure is 20% or higher and the use of empirical antibiotics for 24 to 48 hrs
      pending culture results may be justified and could be used until CBP is excluded.

PMID- 19838145
TI  - Degarelix (firmagon) for prostate cancer.

PMID- 19838146
TI  - Recombinant human antithrombin (ATryn).

PMID- 19838147
TI  - Biodegradable stents and non-biodegradable stents.
AB  - The introduction of the coronary stent in 1986 was one of the most far-reaching
      changes in the practice of interventional cardiology since its inception in 1977.
      Despite all the benefits of the using a metallic drug eluting stent (DES), their
      limitations have generated interest towards biodegradable technology. These
      biodegradable stents, which are made of polymers or metal alloys with or without
      a drug coating, have the potential to scaffold the artery to allow natural
      healing to take place, and then biodegrade. The development of this technology
      has been slow, however several biodegradable stents have entered into clinical
      trials, with many more at the preclinical stage of development. Concurrently
      conventional metallic DES have tried to address their limitations; in particular
      they have sought to repair their damaged reputation following concerns over stent
      thrombosis. Accordingly, stents with a more biocompatible polymer and DES which
      are polymer-free have been developed, and are currently being evaluated in
      clinical trials. This article will review the status of biodegradable stents, and
      these newer DES, during this exciting period in interventional cardiology as
      technology strives to develop the ideal coronary stent.

PMID- 19838148
TI  - Polymer coatings and delayed arterial healing following drug-eluting stent
      implantation.
AB  - The antirestenotic efficacy of drug-eluting stent (DES) technology is based on
      the local delivery and modulated release of cytotoxic drugs targeted at
      inhibition of neointimal hyperplasia. Control of drug-release kinetics is a
      critical component of device efficacy. To date this has been most effectively
      performed by stent coatings comprised of non-erodable (permanent) polymer which
      facilitate drug loading and delay elution of the active drug. In fact all 4 of
      the systems currently approved by the Food and Drug Administration (FDA) use a
      permanent polymer-based drug release system. Balancing the need for lipophilicity
      (to bind active drug) with hydrophilicity (which offers superior
      biocompatibility) is a key challenge in polymer technology. Delayed arterial
      healing (DAH) following DES implantation has been demonstrated in human autopsy
      studies and animal models and is implicated in late thrombotic occlusion and
      delayed loss of antirestenotic efficacy. It is characterised by 1) persistent
      fibrin deposition; 2) delayed endothelialization; 3) chronic inflammation; and 4)
      persistent platelet activation. Within segment heterogeneity in degree of healing
      is typical. Inflammatory response to polymer residue plays an important role and
      may be non-specific (monocyte-macrophage predominant) or hypersensitivity
      related. Failure of early preclinical models to sufficiently predict DAH in man
      was an important problem. Second generation DES attempt to address the issue of
      DAH by using thinner stent struts, lower drug load and more biocompatible
      polymer. At present the focus of development is towards biodegradable polymer
      coatings which offer the attractive prospect of controlled drug-release without
      the potential for late polymer-associated adverse effects. This review highlights
      the role of polymer coatings in determination of DES efficacy, summarises the
      preclinical and clinical evidence linking polymer coatings with DAH and evaluates
      the promise of third generation polymer-free and biodegradable polymer DES.

PMID- 19838149
TI  - Drug-eluting versus bare metal stenting in acute myocardial infarction. A
      clinical review.
AB  - Coronary heart disease is a leading cause of death around the world. The
      treatment of acute myocardial infarction has evolved with the advent of novel
      thrombolytic agents, anticoagulants, antiplatelets, and innovative percutaneous
      techniques. The development of drug-eluting stents has dramatically lowered the
      risk of in-stent restenosis compared to bare metal stents. Clinicians in the
      United States and Europe have begun utilizing DES in the setting of AMI despite
      the fact that no practice guidelines exist to support their use. Lingering
      concerns exist about the reported increased risk of early and late stent
      thrombosis after DES implantation. In this review, we will highlight the >7,500
      patients studied in randomized controlled trials and >30,000 registry patients
      comparing drug-eluting and bare metal stent implantation during acute myocardial
      infarction. In the selected patient populations of the 13 randomized controlled
      trials comparing drug-eluting and bare metal stent implantation, death/re
      infarction/stent thrombosis were not different between groups while target vessel
      revascularization was significantly lower in the drug-eluting stent patients. In
      the "real world" registry studies, mortality/target vessel
      revascularization/stent thrombosis were less frequent in the first year after
      drug-eluting stent implantation while re-infarction was not different between the
      groups. While multiple questions remain regarding long-term follow up and
      especially late stent thrombosis, it appears that drug-eluting stents are
      effective at decreasing target vessel revascularization while not being
      associated with an elevated risk of death/re-infarction/stent thrombosis in the
      first year post myocardial infarction.

PMID- 19838150
TI  - Paclitaxel eluting balloon: from bench to bedside.
AB  - Despite the impressive progress of percutaneous treatment modalities, restenosis
      remains the major Achilles heel of interventional cardiology. Approximately 25%
      of the general population treated for coronary diseases with a bare-metal stent
      and about 10% of patients treated with a drug-eluting stent develop an overgrowth
      of vascular tissue and renarrowing inside the stent, or in-stent restenosis.
      These rates are even greater in diabetics and patients at higher risk of
      restenosis both for clinical presentation (patients in dialysis, low ejection
      fraction) or anatomical characteristics (ostial, bifurcation, long lesions). Non
      stent based local drug delivery and particularly the use of paclitaxel eluting
      balloon (PEB) could be one promising strategy to reduce restenosis. This review
      will briefly explore the different characteristics of PEB devices currently
      present in the market and summarize the results obtained both in animal models
      and clinical practice, giving an indication of the potential field of application
      of this new technology.

PMID- 19838151
TI  - Drug-eluting stent thrombosis.
AB  - Drug-eluting stents (DES) have reduced the risk of repeat revascularization
      procedures by 50-70% compared with bare metal stents across a wide range of
      lesion and patients subsets. Stent thrombosis is a rare but devastating adverse
      event, which results in abrupt closure of the treated artery with the incumbent
      risk of sudden death or myocardial infarction. Although stent thrombosis has been
      recognized as a shortcoming of coronary artery stents since there inception, very
      late stent thrombosis occurring more than one year after stent implantation
      emerged as a new entity complicating the use of DES. The mechanisms leading to
      very late ST are complex and only incompletely understood. Delayed healing and
      incomplete re-endothelialization emerged as prevailing mechanism of thrombosis in
      autopsy studies. Various components of DES may give rise to very late stent
      thrombosis, notably the polymers used for controlled drug-release. Newer
      generation DES attempt to address these concerns by aiming at improved vascular
      healing while maintaining potent neointimal suppression.

PMID- 19838152
TI  - Vascular remodeling after coronary stent implantation.
AB  - Drug eluting stents (DES) have significantly reduced restenosis when compared to
      BMS and are considered the standard of care in the treatment of symptomatic
      coronary artery disease. However, late stent thrombosis has emerged as a major
      concern with the use of first generation DES. Pathologic studies of patients
      dying from late DES thrombosis (first generation sirolimus-eluting stents and
      paclitaxel-eluting stents) showed that DES are associated with delayed healing
      characterized by poor endothelialization of stent struts and persistence of
      fibrin as compared to BMS. Additional risk factors for LST include long lesions,
      left main coronary artery, bifurcation stenting, ruptured plaques, and
      hypersensitivity reactions. Currently, the next generation DES are being
      developed to optimize the three major components of DES: the stent platform, the
      polymer coating and the drug. New technologies include biodegradable polymers and
      stents, polymer free drug delivery and prohealing approaches. Further preclinical
      testing and evaluation through large clinical trials are needed to determine the
      safety and efficacy of future DES in clinical practice.

PMID- 19838153
TI  - Endothelial dysfunction after drug eluting stent implantation.
AB  - Endothelial dysfunction has been implicated in the pathological process of
      coronary artery disease as well as an adverse event after coronary drug eluting
      stent (DES) implantation. In this review, an overview will be given of the
      evidence to date regarding the effects of coronary DES on endothelial function
      obtained from both clinical and experimental studies. Stenting in general and DES
      seem to impair several aspects of endothelial function: provision of a permeable
      barrier function; modulation of adhesion, thrombosis and inflammation; and
      regulation of vascular tone. However, new insights show that the effects of DES
      can extend beyond the stent and peri-stent area: the vascular bed distal to the
      stent, starting with the distal conduit vessels up to the distal
      microvasculature, might be at risk. In addition, insight into the mechanism of
      DES induced endothelial dysfunction has been gained. To finalize this review,
      clinical complications and solutions of DES associated endothelial dysfunction
      will be discussed.

PMID- 19838154
TI  - Drug-eluting stents in primary percutaneous coronary intervention for ST
      elevation myocardial infarction: an up-to-date review of the literature.
AB  - Drug-eluting stents (DES) have been approved by the Food and Drug Administration
      for percutaneous coronary intervention (PCI) in the treatment of stable coronary
      disease but not in the treatment of acute myocardial infarction. In the past,
      treatment of acute myocardial infarction was mainly done via thrombolysis and
      balloon angioplasty. Although the rates of stroke, reocclusion, and
      revascularization were improved with the advent of bare-metal stents, rates of
      restenosis remained high. Primary PCI for ST-elevation myocardial infarction has
      also evolved to include the use of DES in this setting. However, this "off-label"
      use has not been without concerns regarding safety. Stent thrombosis contributes
      to major morbidity and mortality after PCI. Suggestions of higher rates of stent
      thrombosis with the use of DES as compared to bare-metal stents have raised
      questions about DES safety and efficacy. The aim of the authors was to provide an
      in-depth review of the safety of DES in acute myocardial infarction. They have
      therefore reviewed the most up-to-date data, including observational studies,
      randomized trials, and meta-analyses on the use of DES in ST-elevation myocardial
      infarction. Overall, DES appear to have a similar safety profile as compared to
      bare-metal stents in primary PCI in the treatment of ST-elevation myocardial
      infarction. Nevertheless, large-scale randomized studies are needed to further
      evaluate the safety profile of drug-eluting stents as compared to bare-metal
      stents in this setting.

PMID- 19838155
TI  - Evaluation of clopidogrel responsiveness after drug-eluting stent implantation.
AB  - Clopidogrel is a cornerstone of medical therapy in patients with cardiovascular
      disease, reducing the rate of ischemic events in patients with acute coronary
      syndrome, ST elevation myocardial infarction, and those undergoing percutaneous
      coronary intervention (PCI). Prolonged dual antiplatelet therapy with aspirin and
      a thienopyridine is mandated after drug-eluting stent implantation. However,
      there is substantial variability in the pharmacokinetics and pharmacodynamics of
      clopidogrel among individuals, and a lack of effect has been associated with
      adverse outcome after PCI, including drug-eluting stent thrombosis. The
      development of platelet function assays that can be performed in the clinical
      laboratory or at the point-of-care has made it possible to integrate the
      evaluation of clopidogrel response into clinical practice. Clinical utilization
      of platelet function testing requires an understanding of the types of
      methodologies that are available, the interpretation of the results that are
      provided, and the different potential treatment options in patients who are
      identified to be at risk. Several ongoing randomized clinical trials are testing
      the safety and efficacy of individualized antiplatelet therapy based on platelet
      function testing to reduce ischemic events after PCI with drug-eluting stents.

PMID- 19838156
TI  - Coronary bifurcation lesions.
AB  - Coronary bifurcations are prone to develop atherosclerotic plaque due to
      turbulent blood flow and high shear stress. These lesions amount to 15-20% of the
      total number of interventions. The true bifurcation lesion consist of >50%
      diameter obstruction of the main vessel (MV) and of the side branch (SB) in an
      inverted "Y" fashion. Treatment of coronary bifurcation lesions represents a
      challenging area in interventional cardiology but recent advances in percutaneous
      coronary interventions (PCI) have led to the dramatic increase in the number of
      patients successfully treated percutaneously. When compared with non-bifurcation
      interventions, bifurcation interventions have a lower rate of procedural success,
      higher procedural costs, longer hospitalization and a higher clinical and
      angiographic restenosis. Introduction of drug-eluting stents (DES) has resulted
      in a lower event rate and reduction of main vessel (MV) restenosis in comparison
      with historical controls. However, side branch (SB) ostial residual stenosis and
      long-term restenosis remains a problem. Although stenting the MV with provisional
      SB stenting seems to be the prevailing approach, in the era of DES various two
      stent techniques have emerged to allow stenting of the large side branch.

PMID- 19838157
TI  - Anomalous origin of the left anterior descending artery from the right coronary
      artery.

PMID- 19838158
TI  - Aberrant origin of the superior thyroid artery and ascending pharyngeal artery
      from a common trunk arising from the common carotid artery in a hypertensive
      patient with dizziness.

PMID- 19838159
TI  - Generation of human CD40-activated B cells.
AB  - CD40-activated B cells (CD40-B cells) have been identified as an alternative
      source of immuno-stimulatory antigen-presenting cells (APC) for cancer
      immunotherapy. Compared to Dendritic cells (DCs), the best characterized APC,
      CD40-B cells have several distinct biological and technical properties. Similar
      to DCs, B cells show an increased expression of MHC and co-stimulatory molecules
      (Fig.1b), exhibit a strong migratory capacity and present antigen presentation
      efficiently to T cells, after stimulation with interleukin-4 and CD40 ligand
      (CD40L). However, in contrast to immature or mature DCs, CD40-B cells express the
      full lymph node homing triad consisting of CD62L, CCR7/CXCR4, and leukocyte
      function antigen-1 (LFA1, CD11a/CD18), necessary for homing to secondary lymphoid
      organs (Fig.1a). CD40-B cells can be generated without difficulties from very
      small amounts of peripheral blood which can be further expanded in vitro to very
      large amounts of highly-pure CD40-B cells (>10(9) cells per patient) from healthy
      donors as well as cancer patients (Fig.1c,d). In this protocol we demonstrate how
      to obtain fully activated CD40-B cells from human PBMC. Key molecules for the
      cell culture are CD40 ligand, interleukin-4 (IL-4) and cyclosporin A (CsA), which
      are replenished in a 3-4 day culture cycle. For laboratory purposes CD40
      stimulation is provided by NIH/3T3 cells expressing recombinant human CD40 ligand
      (tCD40L NIH/3T3). To avoid contamination with non-transfected cells, expression
      of the human CD40 ligand on the transfectants has to be checked regularly
      (Fig.2). After 14 days CD40-B cell cultures consist of more than 95% pure B cells
      and an expansion of CD40-B cells over 65 days is frequently possible without any
      loss of function. CD40-B cells efficiently take up, process and present antigens
      to T cells. They do not only prime naive, but also expand memory T cells. CD40
      activated B cells can be used to study B-cell activation, differentiation and
      function. Moreover, they represent a promising tool for therapeutic or preventive
      vaccination against tumors.

PMID- 19838160
TI  - Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma.
AB  - Cell surface expression of glucose-regulated protein 78 (GRP78) occurs in several
      types of cancer; however, its role in the behavior of primary cutaneous melanoma
      is not well studied. The association of cell surface GRP78 with other proteins
      such as MTJ1 stimulates cell proliferation. In this study, we characterized the
      pattern of expression of GRP78 and MTJ1 in invasive primary cutaneous melanomas
      and analyzed the relationships between the pattern of expression and various
      clinicopathological parameters. We found two patterns of GRP78 expression in
      invasive primary cutaneous melanoma. One pattern showed a gradual fading of
      protein expression from superficial to deeper levels within the same tumor. The
      second pattern of expression showed a similar fading with an abrupt regaining of
      expression at the deep invasive edge of the melanoma. These two distinct patterns
      of GRP78 expression correlated with both patient survival and depth of tumor
      invasion. A moderate MTJ1 expression was found to be associated with decreased
      patient survival; however, no significant associations were observed between
      patterns of GRP78 and MTJ1 expression. Our study (1) describes two distinct
      patterns of GRP78 in invasive primary cutaneous melanoma, (2) inversely
      correlates regain of GRP78 expression with patient survival, and (3) suggests a
      modifying effect of MTJ1 on GRP78 in enhancing tumor aggressiveness.

PMID- 19838161
TI  - Follicular lymphomas with plasmacytic differentiation include two subtypes.
AB  - Follicular lymphomas with plasmacytic differentiation were described more than
      two decades ago. However, the possibility that some of these reported cases are
      marginal zone lymphomas or composite lymphomas must be considered. In addition,
      it is also uncertain whether follicular lymphomas with plasmacytic
      differentiation have any unique cytogenetic or other features. Therefore,
      fluorescence immunophenotypic and interphase cytogenetic analysis of 14 well
      characterized follicular lymphomas with plasmacytic differentiation was performed
      using a CD138 antibody to identify the plasma cells and with BCL2, BCL6, IGH@ and
      MALT1 break-apart probes and a chromosome 12 centromeric probe. CD10 was
      expressed in 12/14 cases, BCL6 in 12/12 cases and BCL2 in 12/14 cases. At least
      one cytogenetic abnormality was identified in 12/14 cases. The same abnormality
      was present in both the plasmacytic (CD138+) and non-plasmacytic (CD138-)
      component in all 10 evaluable cases. BCL2 rearrangements were present in seven
      cases (5 IGH@ rearranged, 1 IGH@-not rearranged, 1 IGH@-not evaluable), BCL6
      rearrangement in two (1 also with BCL2/IGH@ rearrangement), +12 in 1, +MALT1
      without +18 in 1, IGH@ rearrangement without other abnormalities in 1 and IGH@
      rearranged or partially deleted in 1 case. No cases showed +BCL6 (3q27) or a
      MALT1 rearrangement. All six cases with an isolated BCL2 rearrangement had
      predominantly interfollicular plasmacytic cells whereas, 6/7 cases without the
      translocation had concentrations of intrafollicular or perifollicular plasmacytic
      cells (P<0.005), as did the case with BCL2 and BCL6 translocations. These results
      support the existence of bona fide follicular lymphomas with plasmacytic
      differentiation and support the clonal relationship of the neoplastic lymphoid
      and plasma cells in at least most of these cases. The differential distribution
      of the plasma cells, specifically in relation to the presence or absence of an
      isolated BCL2 rearrangement suggests that the latter cases may be distinctive,
      sharing some features with marginal zone lymphomas.

PMID- 19838162
TI  - Human papillomavirus genotypes in anal intraepithelial neoplasia and anal
      carcinoma as detected in tissue biopsies.
AB  - Human papillomavirus (HPV) infection strongly correlates with the development of
      anal intraepithelial neoplasias and carcinomas; however, few studies have
      characterized the distribution of the specific subtypes of the virus in the
      varying grades of dysplasia. This report characterizes the distribution of HPV
      16/18 in surgical specimens with anal intraepithelial neoplasia (AIN) I-III and
      histological variants of anal carcinoma. A total of 111 anal surgical specimens
      with no dysplasia (10), AIN I-III (53), and anal carcinomas (48) were evaluated
      for the presence of high-risk HPV infection and subtyped by nested PCR or the
      Invader Assay. High-risk virus types were detected in progressively greater
      number of anal intraepithelial lesions from 56% in low grade to 88% in high
      grade. Type 16 was the prevalent subtype and was noted in 28% of low grade and
      68% of high-grade lesions. Moderate dysplasias showed type 16 in 20%, a
      prevalence similar to that in low-grade lesions. The non-16/18 subtypes of the
      virus predominated and were present in 50% of the cases. Most (89%) squamous
      carcinomas were associated with high-risk viruses, 68% with type 16, a prevalence
      similar to that noted in high-grade dysplasia. Non-16/18 subtypes were
      encountered more frequently in squamous carcinomas from immunodeficient
      individuals (57% cases) as compared with immunocompetent individuals (18% cases).
      The similarity in the prevalence of type 16 in high-grade dysplasia and squamous
      carcinomas suggests that anal intraepithelial lesion III is the true precursor of
      squamous carcinoma and warrants aggressive management. Anal intraepithelial
      lesions II showed a virus distribution that was similar to low-grade dysplasia.
      In addition, a subset of these that were associated with type 16 or 18 showed
      progression, whereas those associated with non-16/18 subtypes regressed, thereby
      raising the possibility of conservative management for these lesions.

PMID- 19838163
TI  - Lactate dehydrogenase 5 expression in melanoma increases with disease progression
      and is associated with expression of Bcl-XL and Mcl-1, but not Bcl-2 proteins.
AB  - The serum level of lactate dehydrogenase (LDH) is an important predictor of
      prognosis and treatment response in melanoma patients. It is unknown whether the
      expression of LDH-5 in tissue sections also has prognostic significance and
      whether it is related to the expression of the anti-apoptotic proteins, Bcl-2,
      Bcl-XL and Mcl-1, and endoplasmic reticulum stress protein glucose-regulated
      protein 78 (GRP78). Identification of an association between LDH-5 expression and
      anti-apoptotic proteins may have important therapeutic implications for melanoma
      patients. Sections from 159 pigmented lesions, including nevi and melanoma at
      different stages of progression were studied by immunohistochemistry. Correlation
      of LDH-5 expression with clinicopathological factors and with the expression of
      Bcl-2, Bcl-XL, Mcl-1 and GRP78 was examined. LDH-5 was detected at low levels in
      6 of 10 compound nevi (60%) and 6 of 10 dysplastic nevi (60%). The percentage of
      positive cases was greater in thin (<or=1.0 mm) (74%) and thick primary melanoma
      (>1.0 mm) (95%) and in metastatic melanoma in the skin (100%) and lymph node
      (81%). The immunoreactive score was highly related to progression of melanoma
      (P<0.0001). LDH-5 expression was positively associated with increasing tumor
      thickness (P=0.02) and dermal tumor mitotic rate (P=0.02). LDH-5 above the median
      immunoreactive score was associated with reduced disease-free survival and
      overall survival (P<0.02). LDH-5 expression was negatively associated with Bcl-2
      expression. In contrast, LDH-5 expression was strongly associated with Bcl-XL and
      Mcl-1 expression and also positively associated with GRP78 expression (P<0.0001).
      The low Bcl-2 expression in melanomas with high LDH-5 expression provides an
      explanation for the poor response of patients with high serum LDH levels to
      treatment with the Bcl-2 antisense drug 'Genasense'. The strong correlation of
      LDH-5 expression with Mcl-1 expression suggests that treatment strategies
      inhibiting the activity of Mcl-1 in melanoma patients should be investigated.

PMID- 19838164
TI  - Grading of gastric foveolar-type dysplasia in Barrett's esophagus.
AB  - Dysplasia is the gold standard biomarker of cancer risk in Barrett's esophagus,
      but its diagnosis remains difficult. This is due in part to its multitude of
      histological appearances. One aspect receiving little attention concerns gastric
      type Barrett's dysplasia, which is distinctly different from the well-established
      intestinal variant. Recognition of gastric-type dysplasia and development of
      separate grading criteria are required. The prevalence, diagnostic criteria, and
      natural history of gastric-type Barrett's dysplasia were systematically evaluated
      in 1854 endoscopic biopsies from a cohort of 200 consecutive Barrett's dysplasia
      patients. Goblet cells were present in all cases, confirming the utility of this
      defining feature of Barrett's esophagus. The prevalence of Barrett's gastric-type
      dysplasia was 15% at the patient level (30 of 200 patients) and 20% at the biopsy
      level (166 of 852 dysplastic biopsies). Gastric-type dysplasia uniformly showed
      non-stratified, basally oriented nuclei as the major criterion for distinguishing
      it from intestinal-type Barrett's dysplasia. As such, loss of nuclear polarity,
      as the most objective criterion to distinguish intestinal-type low- and high
      grade dysplasia, cannot be applied to gastric-type dysplasia. Rather,
      discriminatory features included increased nuclear size with a high-grade
      dysplasia cutoff by receiver operating characteristic (ROC) analysis
      approximating 3-4 times the size of a mature lymphocyte, providing an optimal
      sensitivity, specificity, and area under the curve of 0.78, 0.90, and 0.90 (95%
      CI: (0.87, 0.93)), respectively. Crowded, irregular glandular architecture
      (P<0.001) was more common in high-grade lesions (P<0.001), as was eosinophilic
      and oncocytic cytoplasm relative to the mucinous cytoplasm (P<0.001), prominent
      nucleoli (P<0.001), mild nuclear pleomorphism (P<0.001), and villiform
      architecture (P<0.001). During follow-up, 64% (7 of 11) of patients with pure
      gastric and 26% (5 of 19) with mixed gastric and intestinal dysplasia underwent
      neoplastic progression. The recognition of Barrett's gastric-type dysplasia and
      use of the proposed grading criteria should promote better diagnostic
      classification of the Barrett's neoplastic spectrum.

PMID- 19838165
TI  - Optomechanical crystals.
AB  - Periodicity in materials yields interesting and useful phenomena. Applied to the
      propagation of light, periodicity gives rise to photonic crystals, which can be
      precisely engineered for such applications as guiding and dispersing optical
      beams, tightly confining and trapping light resonantly, and enhancing nonlinear
      optical interactions. Photonic crystals can also be formed into planar lightwave
      circuits for the integration of optical and electrical microsystems. In a
      photonic crystal, the periodicity of the host medium is used to manipulate the
      properties of light, whereas a phononic crystal uses periodicity to manipulate
      mechanical vibrations. As has been demonstrated in studies of Raman-like
      scattering in epitaxially grown vertical cavity structures and photonic crystal
      fibres, the simultaneous confinement of mechanical and optical modes in periodic
      structures can lead to greatly enhanced light-matter interactions. A logical next
      step is thus to create planar circuits that act as both photonic and phononic
      crystals: optomechanical crystals. Here we describe the design, fabrication and
      characterization of a planar, silicon-chip-based optomechanical crystal capable
      of co-localizing and strongly coupling 200-terahertz photons and 2-gigahertz
      phonons. These planar optomechanical crystals bring the powerful techniques of
      optics and photonic crystals to bear on phononic crystals, providing exquisitely
      sensitive (near quantum-limited), optical measurements of mechanical vibrations,
      while simultaneously providing strong nonlinear interactions for optics in a
      large and technologically relevant range of frequencies.

PMID- 19838166
TI  - Genome evolution and adaptation in a long-term experiment with Escherichia coli.
AB  - The relationship between rates of genomic evolution and organismal adaptation
      remains uncertain, despite considerable interest. The feasibility of obtaining
      genome sequences from experimentally evolving populations offers the opportunity
      to investigate this relationship with new precision. Here we sequence genomes
      sampled through 40,000 generations from a laboratory population of Escherichia
      coli. Although adaptation decelerated sharply, genomic evolution was nearly
      constant for 20,000 generations. Such clock-like regularity is usually viewed as
      the signature of neutral evolution, but several lines of evidence indicate that
      almost all of these mutations were beneficial. This same population later evolved
      an elevated mutation rate and accumulated hundreds of additional mutations
      dominated by a neutral signature. Thus, the coupling between genomic and adaptive
      evolution is complex and can be counterintuitive even in a constant environment.
      In particular, beneficial substitutions were surprisingly uniform over time,
      whereas neutral substitutions were highly variable.

PMID- 19838168
TI  - A chemical platform for improved induction of human iPSCs.
AB  - The slow kinetics and low efficiency of reprogramming methods to generate human
      induced pluripotent stem cells (iPSCs) impose major limitations on their utility
      in biomedical applications. Here we describe a chemical approach that
      dramatically improves (200-fold) the efficiency of iPSC generation from human
      fibroblasts, within seven days of treatment. This will provide a basis for
      developing safer, more efficient, nonviral methods for reprogramming human
      somatic cells.

PMID- 19838167
TI  - What recent ribosome structures have revealed about the mechanism of translation.
AB  - The high-resolution structures of ribosomal subunits published in 2000 have
      revolutionized the field of protein translation. They facilitated the
      determination and interpretation of functional complexes of the ribosome by
      crystallography and electron microscopy. Knowledge of the precise positions of
      residues in the ribosome in various states has facilitated increasingly
      sophisticated biochemical and genetic experiments, as well as the use of new
      methods such as single-molecule kinetics. In this review, we discuss how the
      interaction between structural and functional studies over the last decade has
      led to a deeper understanding of the complex mechanisms underlying translation.

PMID- 19838169
TI  - Enrichment of glycopeptides for glycan structure and attachment site
      identification.
AB  - We present a method to enrich for glycoproteins from proteomic samples.
      Sialylated glycoproteins were selectively periodate-oxidized, captured on
      hydrazide beads, trypsinized and released by acid hydrolysis of sialic acid
      glycosidic bonds. Mass spectrometric fragment analysis allowed identification of
      glycan structures, and additional fragmentation of deglycosylated ions yielded
      peptide sequence information, which allowed glycan attachment site and protein
      identification. We identified 36 N-linked and 44 O-linked glycosylation sites on
      glycoproteins from human cerebrospinal fluid.

PMID- 19838170
TI  - Visual proteomics of the human pathogen Leptospira interrogans.
AB  - Systems biology conceptualizes biological systems as dynamic networks of
      interacting elements, whereby functionally important properties are thought to
      emerge from the structure of such networks. Owing to the ubiquitous role of
      complexes of interacting proteins in biological systems, their subunit
      composition and temporal and spatial arrangement within the cell are of
      particular interest. 'Visual proteomics' attempts to localize individual
      macromolecular complexes inside of intact cells by template matching reference
      structures into cryo-electron tomograms. Here we combined quantitative mass
      spectrometry and cryo-electron tomography to detect, count and localize specific
      protein complexes in the cytoplasm of the human pathogen Leptospira interrogans.
      We describe a scoring function for visual proteomics and assess its performance
      and accuracy under realistic conditions. We discuss current and general
      limitations of the approach, as well as expected improvements in the future.

PMID- 19838171
TI  - DNA damage signalling prevents deleterious telomere addition at DNA breaks.
AB  - The response to DNA damage involves regulation of several essential processes to
      maximize the accuracy of DNA damage repair and cell survival. Telomerase has the
      potential to interfere with repair by inappropriately adding telomeres to DNA
      breaks. It was unknown whether cells modulate telomerase in response to DNA
      damage to increase the accuracy of repair. Here, we report that telomerase action
      is regulated as a part of the cellular response to DNA double-strand breaks
      (DSBs). Using yeast, we show that the main ATR/Mec1 DNA damage signalling pathway
      regulates telomerase action at DSBs. After DNA damage, MEC1-RAD53-DUN1-dependent
      phosphorylation of the telomerase inhibitor Pif1 occurs. Using a separation of
      function PIF1 mutation, we show that this phosphorylation is specifically
      required for the Pif1-mediated telomerase inhibition that takes place at DNA
      breaks, but not for that at telomeres. Hence DNA damage signalling down-modulates
      telomerase action at DNA breaks through Pif1 phosphorylation, thus preventing
      aberrant healing of broken DNA ends by telomerase. These findings uncover a new
      regulatory mechanism that coordinates competing DNA end-processing activities and
      thereby promotes DNA repair accuracy and genome integrity.

PMID- 19838172
TI  - Topoisomerase I suppresses genomic instability by preventing interference between
      replication and transcription.
AB  - Topoisomerase I (Top1) is a key enzyme in functioning at the interface between
      DNA replication, transcription and mRNA maturation. Here, we show that Top1
      suppresses genomic instability in mammalian cells by preventing a conflict
      between transcription and DNA replication. Using DNA combing and ChIP (chromatin
      immunoprecipitation)-on-chip, we found that Top1-deficient cells accumulate
      stalled replication forks and chromosome breaks in S phase, and that breaks occur
      preferentially at gene-rich regions of the genome. Notably, these phenotypes were
      suppressed by preventing the formation of RNA-DNA hybrids (R-loops) during
      transcription. Moreover, these defects could be mimicked by depletion of the
      splicing factor ASF/SF2 (alternative splicing factor/splicing factor 2), which
      interacts functionally with Top1. Taken together, these data indicate that Top1
      prevents replication fork collapse by suppressing the formation of R-loops in an
      ASF/SF2-dependent manner. We propose that interference between replication and
      transcription represents a major source of spontaneous replication stress, which
      could drive genomic instability during the early stages of tumorigenesis.

PMID- 19838173
TI  - FLIP-mediated autophagy regulation in cell death control.
AB  - Autophagy is an active homeostatic degradation process for the removal or
      turnover of cytoplasmic components wherein the LC3 ubiquitin-like protein
      undergoes an Atg7 E1-like enzyme/Atg3 E2-like enzyme-mediated conjugation process
      to induce autophagosome biogenesis. Besides its cytoprotective role, autophagy
      acts on cell death when it is abnormally upregulated. Thus, the autophagy pathway
      requires tight regulation to ensure that this degradative process is well
      balanced. Two death effector domains (DED1/2) containing cellular FLICE-like
      inhibitor protein (cFLIP) and viral FLIP (vFLIP) of Kaposi's sarcoma-associated
      herpesvirus (KSHV), Herpesvirus saimiri (HVS), and Molluscum contagiosum virus
      (MCV) protect cells from apoptosis mediated by death receptors. Here, we report
      that cellular and viral FLIPs suppress autophagy by preventing Atg3 from binding
      and processing LC3. Consequently, FLIP expression effectively represses cell
      death with autophagy, as induced by rapamycin, an mTor inhibitor and an effective
      anti-tumour drug against KSHV-induced Kaposi's sarcoma (KS) and primary effusion
      lymphoma (PEL). Remarkably, either a DED1 alpha2-helix ten amino-acid (alpha2)
      peptide or a DED2 alpha4-helix twelve amino-acid (alpha4) peptide of FLIP is
      individually sufficient for binding FLIP itself and Atg3, with the peptide
      interactions effectively suppressing Atg3-FLIP interaction without affecting Atg3
      LC3 interaction, resulting in robust cell death with autophagy. Our study thus
      identifies a checkpoint of the autophagy pathway where cellular and viral FLIPs
      limit the Atg3-mediated step of LC3 conjugation to regulate autophagosome
      biogenesis. Furthermore, the FLIP-derived short peptides induce growth
      suppression and cell death with autophagy, representing biologically active
      molecules for potential anti-cancer therapies.

PMID- 19838174
TI  - Analysis of the gamma-secretase interactome and validation of its association
      with tetraspanin-enriched microdomains.
AB  - Gamma-secretase, an aspartyl protease that belongs to the iCLiPs (intramembrane
      cleaving proteases) family, is a multiprotein complex that consists of presenilin
      (PS), nicastrin (NCT), Aph-1 and Pen-2 (ref. 1). It is responsible for generation
      of the beta-amyloid peptide (Abeta), the primary component of senile plaques in
      the brains of patients with Alzheimer's disease. Although the four components are
      necessary and sufficient for gamma-secretase activity, additional proteins are
      possibly involved in its regulation. Consequently, we purified proteins
      associated with the active gamma-secretase complex from reconstituted PS
      deficient fibroblasts, using tandem affinity purification (TAP) and identified a
      series of proteins that transiently interact with the gamma-secretase complex and
      are probably involved in complex maturation, membrane trafficking and,
      importantly, the tetraspanin web. Tetraspanins form detergent-resistant
      microdomains in the cell membrane and regulate cell adhesion, cell signalling and
      proteolysis. Association of the gamma-secretase complex with tetraspanin-enriched
      microdomains provides an explanation for the previously documented localization
      of gamma-secretase to raft-like domains. Thus, these studies suggest that
      maintenance of the integrity of tetraspanin microdomains contributes to the
      refinement of proteolytic activity of the gamma-secretase complex.

PMID- 19838175
TI  - Localized and reversible TGFbeta signalling switches breast cancer cells from
      cohesive to single cell motility.
AB  - Here we use intravital imaging to demonstrate a reversible transition to a motile
      state as breast cancer cells spread. Imaging primary tumours revealed
      heterogeneity in cell morphology and motility. Two distinct modes of motility
      were observed: collective and single-celled. By monitoring the localization of
      Smad2 and the activity of a TGFbeta-dependent reporter gene during breast cancer
      cell dissemination, we demonstrate that TGFbeta signalling is transiently and
      locally activated in motile single cells. TGFbeta1 switches cells from cohesive
      to single cell motility through a transcriptional program involving Smad4, EGFR,
      Nedd9, M-RIP, FARP and RhoC. Blockade of TGFbeta signalling prevented cells
      moving singly in vivo but did not inhibit cells moving collectively. Cells
      restricted to collective invasion were capable of lymphatic invasion but not
      blood-borne metastasis. Constitutive TGFbeta signalling promoted single cell
      motility and intravasation but reduced subsequent growth in the lungs. Thus,
      transient TGFbeta signalling is essential for blood-borne metastasis.

PMID- 19838176
TI  - TGF-beta helps cells fly solo.

PMID- 19838177
TI  - Formation and maintenance of Alzheimer's disease beta-amyloid plaques in the
      absence of microglia.
AB  - In Alzheimer's disease, microglia cluster around beta-amyloid deposits,
      suggesting that these cells are important for amyloid plaque formation,
      maintenance and/or clearance. We crossed two distinct APP transgenic mouse
      strains with CD11b-HSVTK mice, in which nearly complete ablation of microglia was
      achieved for up to 4 weeks after ganciclovir application. Neither amyloid plaque
      formation and maintenance nor amyloid-associated neuritic dystrophy depended on
      the presence of microglia.

PMID- 19838178
TI  - The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic
      timer of myelination.
AB  - The basic helix-loop-helix transcription factor Olig1 promotes oligodendrocyte
      maturation and is required for myelin repair. We characterized an Olig1-regulated
      G protein-coupled receptor, GPR17, whose function is to oppose the action of
      Olig1. Gpr17 was restricted to oligodendrocyte lineage cells, but was
      downregulated during the peak period of myelination and in adulthood. Transgenic
      mice with sustained Gpr17 expression in oligodendrocytes exhibited stereotypic
      features of myelinating disorders in the CNS. Gpr17 overexpression inhibited
      oligodendrocyte differentiation and maturation both in vivo and in vitro.
      Conversely, Gpr17 knockout mice showed early onset of oligodendrocyte
      myelination. The opposing action of Gpr17 on oligodendrocyte maturation reflects,
      at least partially, upregulation and nuclear translocation of the potent
      oligodendrocyte differentiation inhibitors ID2/4. Collectively, these findings
      suggest that GPR17 orchestrates the transition between immature and myelinating
      oligodendrocytes via an ID protein-mediated negative regulation and may serve as
      a potential therapeutic target for CNS myelin repair.

PMID- 19838179
TI  - Sip1 regulates sequential fate decisions by feedback signaling from postmitotic
      neurons to progenitors.
AB  - The fate of cortical progenitors, which progressively generate neurons and glial
      cells during development, is determined by temporally and spatially regulated
      signaling mechanisms. We found that the transcription factor Sip1 (Zfhx1b), which
      is produced at high levels in postmitotic neocortical neurons, regulates
      progenitor fate non-cell autonomously. Conditional deletion of Sip1 in young
      neurons induced premature production of upper-layer neurons at the expense of
      deep layers, precocious and increased generation of glial precursors, and
      enhanced postnatal astrocytogenesis. The premature upper-layer generation
      coincided with overexpression of the neurotrophin-3 (Ntf3) gene and upregulation
      of fibroblast growth factor 9 (Fgf9) gene expression preceded precocious
      gliogenesis. Exogenous application of Fgf9 to mouse cortical slices induced
      excessive generation of glial precursors in the germinal zone. Our data suggest
      that Sip1 restrains the production of signaling factors in postmitotic neurons
      that feed back to progenitors to regulate the timing of cell fate switch and the
      number of neurons and glial cells throughout corticogenesis.

PMID- 19838180
TI  - Functional consequences of animal-to-animal variation in circuit parameters.
AB  - How different are the neuronal circuits for a given behavior across individual
      animals? To address this question, we measured multiple cellular and synaptic
      parameters in individual preparations to see how they correlated with circuit
      function, using neurons and synapses in the pyloric circuit of the stomatogastric
      ganglion of the crab Cancer borealis. There was considerable preparation-to
      preparation variability in the strength of two identified synapses, in the
      amplitude of a modulator-evoked current and in the expression of six ion channel
      genes. Nonetheless, we found strong correlations across preparations among these
      parameters and attributes of circuit performance. These data illustrate the
      importance of making multidimensional measurements from single preparations for
      understanding how variability in circuit output is related to the variability of
      multiple circuit parameters.

PMID- 19838181
TI  - Small-molecule-directed nanoparticle assembly towards stimuli-responsive
      nanocomposites.
AB  - Precise control of the spatial organization of nanoscopic building blocks, such
      as nanoparticles, over multiple length scales is a bottleneck in the 'bottom-up'
      generation of technologically important materials. Only a few approaches have
      been shown to achieve nanoparticle assemblies without surface modification. We
      demonstrate a simple yet versatile approach to produce stimuli-responsive
      hierarchical assemblies of readily available nanoparticles by combining small
      molecules and block copolymers. Organization of nanoparticles into one-, two- and
      three-dimensional arrays with controlled inter-particle separation and ordering
      is achieved without chemical modification of either the nanoparticles or block
      copolymers. Nanocomposites responsive to heat and light are demonstrated, where
      the spatial distribution of the nanoparticles can be varied by exposure to heat
      or light or changing the local environment. The approach described is applicable
      to a wide range of nanoparticles and compatible with existing fabrication
      processes, thereby enabling a non-disruptive approach for the generation of
      functional devices.

PMID- 19838183
TI  - Solution-deposited sodium beta-alumina gate dielectrics for low-voltage and
      transparent field-effect transistors.
AB  - Sodium beta-alumina (SBA) has high two-dimensional conductivity, owing to mobile
      sodium ions in lattice planes, between which are insulating AlO(x) layers. SBA
      can provide high capacitance perpendicular to the planes, while causing
      negligible leakage current owing to the lack of electron carriers and limited
      mobility of sodium ions through the aluminium oxide layers. Here, we describe sol
      gel-beta-alumina films as transistor gate dielectrics with solution-deposited
      zinc-oxide-based semiconductors and indium tin oxide (ITO) gate electrodes. The
      transistors operate in air with a few volts input. The highest electron mobility,
      28.0 cm2 V(-1) s(-1), was from zinc tin oxide (ZTO), with an on/off ratio of 2 x
      10(4). ZTO over a lower-temperature, amorphous dielectric, had a mobility of 10
      cm2 V(-1) s(-1). We also used silicon wafer and flexible polyimide-aluminium foil
      substrates for solution-processed n-type oxide and organic transistors. Using
      poly(3,4-ethylenedioxythiophene) poly(styrenesulphonate) conducting polymer
      electrodes, we prepared an all-solution-processed, low-voltage transparent oxide
      transistor on an ITO glass substrate.

PMID- 19838184
TI  - Application of a quartz-crystal microbalance to measure ionic fluxes in
      microporous carbons for energy storage.
AB  - Fast ionic transport in microporous activated-carbon electrodes is a prerequisite
      for the effective energy storage in electrochemical supercapacitors. However, the
      quartz-crystal microbalance (QCM), a direct tool to measure ionic fluxes in
      electrochemical systems, has not yet been used for studying transport phenomena
      in activated carbons (except for an early report on carbon nanotubes).
      Conventional electroanalytical and suitable surface and structure-analysis
      techniques provide limited prognostic information on this matter. It has been
      demonstrated herein that the QCM response of typical microporous activated
      carbons can serve as a gravimetric probe of the concentration and compositional
      changes in their pore volume. This allowed direct monitoring of the ionic fluxes,
      which depended strongly on the electrode's point of zero change, pore width, ion
      size and cycling conditions (polarization amplitude, charge/discharge depth and
      so on). The information on the nature of ionic fluxes into activated carbons is
      critical for promoting improvements in the performance of electrochemical
      supercapacitors, membrane technologies and (electro/bio)chemical sensors.

PMID- 19838182
TI  - Material properties of the cell dictate stress-induced spreading and
      differentiation in embryonic stem cells.
AB  - Growing evidence suggests that physical microenvironments and mechanical
      stresses, in addition to soluble factors, help direct mesenchymal-stem-cell fate.
      However, biological responses to a local force in embryonic stem cells remain
      elusive. Here we show that a local cyclic stress through focal adhesions induced
      spreading in mouse embryonic stem cells but not in mouse embryonic stem-cell
      differentiated cells, which were ten times stiffer. This response was dictated by
      the cell material property (cell softness), suggesting that a threshold cell
      deformation is the key setpoint for triggering spreading responses. Traction
      quantification and pharmacological or shRNA intervention revealed that myosin II
      contractility, F-actin, Src or cdc42 were essential in the spreading response.
      The applied stress led to oct3/4 gene downregulation in mES cells. Our findings
      demonstrate that cell softness dictates cellular sensitivity to force, suggesting
      that local small forces might have far more important roles in early development
      of soft embryos than previously appreciated.

PMID- 19838185
TI  - Non-entropic and reversible long-range deformation of an encapsulating
      bioelastomer.
AB  - Encapsulation is a widespread biological process particularly in the formation of
      protective egg cases of oviparous animals. The egg capsule wall of the channelled
      whelk Busycon canaliculum is an effective shock absorber with high reversible
      extensibility and a stiffness that changes significantly during extension. Here
      we show that post-stretch recovery in egg capsules is not driven by entropic
      forces as it is in rubber. Indeed, at fixed strain, force decreases linearly with
      increasing temperature, whereas in rubber elasticity the force increases.
      Instead, capsule wall recovery is associated with the internal energy arising
      from the facile and reversible structural alpha-helix <--> beta-sheet transition
      of egg capsule proteins during extension. This behaviour is extraordinary in the
      magnitude of energy dissipated and speed of recovery and is reminiscent of strain
      induced crystallization in some polymeric fibres and of superelastic deformations
      associated with diffusionless phase transitions in shape-memory alloys.

PMID- 19838186
TI  - Enhanced ordering temperatures in antiferromagnetic manganite superlattices.
AB  - The disorder inherent to doping by cation substitution in the complex oxides can
      have profound effects on collective-ordered states. Here, we demonstrate that
      cation-site ordering achieved through digital-synthesis techniques can
      dramatically enhance the antiferromagnetic ordering temperatures of manganite
      films. Cation-ordered (LaMnO3)m/(SrMnO3)2m superlattices show Neel temperatures
      (TN) that are the highest of any La(1-x)Sr(x)MnO3 compound, approximately 70 K
      greater than compositionally equivalent randomly doped La(1/3)Sr(2/3)MnO3. The
      antiferromagnetic order is A-type, consisting of in-plane double-exchange
      mediated ferromagnetic sheets coupled antiferromagnetically along the out-of
      plane direction. Through synchrotron X-ray scattering, we have discovered an in
      plane structural modulation that reduces the charge itinerancy and hence the
      ordering temperature within the ferromagnetic sheets, thereby limiting TN. This
      modulation is mitigated and driven to long wavelengths by cation ordering,
      enabling the higher TN values of the superlattices. These results provide insight
      into how cation-site ordering can enhance cooperative behaviour in oxides through
      subtle structural phenomena.

PMID- 19838188
TI  - Crystal structure of TNFalpha complexed with a poxvirus MHC-related TNF binding
      protein.
AB  - The poxvirus 2L protein binds tumor necrosis factor-alpha (TNFalpha) to inhibit
      host antiviral and immune responses. The 2.8-A 2L-TNFalpha structure reveals
      three symmetrically arranged 2L molecules per TNFalpha trimer. 2L resembles class
      I major histocompatibility complex (MHC) molecules but lacks a peptide-binding
      groove and beta2-microglobulin light chain. Overlap between the 2L and host TNF
      receptor-binding sites on TNFalpha rationalizes 2L inhibition of TNFalpha-TNF
      receptor interactions and prevention of TNFalpha-induced immune responses.

PMID- 19838187
TI  - Ago-TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps.
AB  - MicroRNAs (miRNAs) silence the expression of their mRNA targets mainly by
      promoting mRNA decay. The mechanism, kinetics and participating enzymes for miRNA
      mediated decay in mammalian cells remain largely unclear. Combining the
      approaches of transcriptional pulsing, RNA tethering, overexpression of dominant
      negative mutants, and siRNA-mediated gene knockdown, we show that let-7 miRNA
      induced silencing complexes (miRISCs), which contain the proteins Argonaute (Ago)
      and TNRC6 (also known as GW182), trigger very rapid mRNA decay by inducing
      accelerated biphasic deadenylation mediated by Pan2-Pan3 and Ccr4-Caf1
      deadenylase complexes followed by Dcp1-Dcp2 complex-directed decapping in
      mammalian cells. When tethered to mRNAs, all four human Ago proteins and TNRC6C
      are each able to recapitulate the two deadenylation steps. Two conserved human
      Ago2 phenylalanines (Phe470 and Phe505) are critical for recruiting TNRC6 to
      promote deadenylation. These findings indicate that promotion of biphasic
      deadenylation to trigger mRNA decay is an intrinsic property of miRISCs.

PMID- 19838189
TI  - Hsp90 charged-linker truncation reverses the functional consequences of weakened
      hydrophobic contacts in the N domain.
AB  - Heat shock protein 90 (Hsp90) is an essential molecular chaperone in eukaryotes,
      as it regulates diverse signal transduction nodes that integrate numerous
      environmental cues to maintain cellular homeostasis. Hsp90 also is secreted from
      normal and transformed cells and regulates cell motility. Here, we have
      identified a conserved hydrophobic motif in a beta-strand at the boundary between
      the N domain and charged linker of Hsp90, whose mutation not only abrogated Hsp90
      secretion but also inhibited its function. These Hsp90 mutants lacked chaperone
      activity in vitro and failed to support yeast viability. Notably, truncation of
      the charged linker reduced solvent accessibility of this beta-strand and restored
      chaperone activity to these mutants. These data underscore the importance of beta
      strand 8 for Hsp90 function and demonstrate that the functional consequences of
      weakened hydrophobic contacts in this region are reversed by charged-linker
      truncation.

PMID- 19838190
TI  - A two-pronged strategy to suppress host protein synthesis by SARS coronavirus
      Nsp1 protein.
AB  - Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene
      expression, including type I interferon production, by promoting host mRNA
      degradation and inhibiting host translation, in infected cells. We present
      evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation
      and gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the
      translational activity of the 40S subunits. Furthermore, the nsp1-40S ribosome
      complex induced the modification of the 5' region of capped mRNA template and
      rendered the template RNA translationally incompetent. Nsp1 also induced RNA
      cleavage in templates carrying the internal ribosome entry site (IRES) from
      encephalomyocarditis virus, but not in those carrying IRES elements from
      hepatitis C or cricket paralysis viruses, demonstrating that the nsp1-induced RNA
      modification was template-dependent. We speculate that the mRNAs that underwent
      the nsp1-mediated modification are marked for rapid turnover by the host RNA
      degradation machinery.

PMID- 19838191
TI  - Positive selection of DNA-protein interactions in mammalian cells through
      phenotypic coupling with retrovirus production.
AB  - Through the shuffling of predefined modular zinc finger domains with predictable
      target site recognition in vitro, we have generated a large repertoire of
      artificial transcription factors with five zinc finger domains (TF(ZF)s). Here we
      report an effective strategy for the selection of ATF libraries by coupling
      expression of transcriptional activators of the promoter of interest to the
      enhanced production of retroviral vector particles transferring the TF(ZF)
      encoding gene. Using this strategy, we successfully selected specific TF(ZF)s
      that upregulate the expression of the gamma-globin promoter. Selected
      transcription factors induced the expression of gamma-globin when coupled to an
      activation domain and reduced expression when linked to a repression domain. This
      new retroviral approach might be used to select other TF(ZF)s but might also be
      generalized for the selection of other protein and small-molecule interactions.

PMID- 19838192
TI  - Global patterns of cis variation in human cells revealed by high-density allelic
      expression analysis.
AB  - Cis-acting variants altering gene expression are a source of phenotypic
      differences. The cis-acting components of expression variation can be identified
      through the mapping of differences in allelic expression (AE), which is the
      measure of relative expression between two allelic transcripts. We generated a
      map of AE associated SNPs using quantitative measurements of AE on Illumina
      Human1M BeadChips. In 53 lymphoblastoid cell lines derived from donors of
      European descent, we identified common cis variants affecting 30% (2935/9751) of
      the measured RefSeq transcripts at 0.001 permutation significance. The pervasive
      influence of cis-regulatory variants, which explain 50% of population variation
      in AE, extend to full-length transcripts and their isoforms as well as to
      unannotated transcripts. These strong effects facilitate fine mapping of cis
      regulatory SNPs, as demonstrated by dissection of heritable control of
      transcripts in the systemic lupus erythematosus-associated C8orf13-BLK region in
      chromosome 8. The dense collection of associations will facilitate large-scale
      isolation of cis-regulatory SNPs.

PMID- 19838193
TI  - Genome-wide association study in a Chinese Han population identifies nine new
      susceptibility loci for systemic lupus erythematosus.
AB  - We performed a genome-wide association study (GWAS) of systemic lupus
      erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and
      1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in
      two additional cohorts (3,152 cases and 7,050 controls). We identified nine new
      susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22,
      11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and
      confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21
      and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)).
      Comparison with previous GWAS findings highlighted the genetic heterogeneity of
      SLE susceptibility between Chinese Han and European populations. This study not
      only advances our understanding of the genetic basis of SLE but also highlights
      the value of performing GWAS in diverse ancestral populations.

PMID- 19838194
TI  - Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute
      lymphoblastic leukemia.
AB  - Aneuploidy and translocations are hallmarks of B-progenitor acute lymphoblastic
      leukemia (ALL), but many individuals with this cancer lack recurring chromosomal
      alterations. Here we report a recurring interstitial deletion of the
      pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that
      juxtaposes the first, noncoding exon of P2RY8 with the coding region of CRLF2. We
      identified the P2RY8-CRLF2 fusion in 7% of individuals with B-progenitor ALL and
      53% of individuals with ALL associated with Down syndrome. CRLF2 alteration was
      associated with activating JAK mutations, and expression of human P2RY8-CRLF2
      together with mutated mouse Jak2 resulted in constitutive Jak-Stat activation and
      cytokine-independent growth of Ba/F3 cells overexpressing interleukin-7 receptor
      alpha. Our findings indicate that these two genetic lesions together contribute
      to leukemogenesis in B-progenitor ALL.

PMID- 19838195
TI  - A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10
      as risk loci for systemic lupus erythematosus.
AB  - Genome-wide association studies have recently identified at least 15
      susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional
      risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of
      association to SLE (P < 0.05) in a genome-wide study and genotyped them in an
      independent sample of 1,963 cases and 4,329 controls. This replication effort
      identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio
      (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10
      (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5).
      A candidate screen of alleles previously associated with other autoimmune
      diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1,
      CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and
      candidate SLE susceptibility loci and implicate several key immunologic pathways
      in SLE pathogenesis.

PMID- 19838196
TI  - Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe
      sensory and autonomic neuropathy.
AB  - Hereditary sensory and autonomic neuropathy type II (HSAN II) leads to severe
      mutilations because of impaired nociception and autonomic dysfunction. Here we
      show that loss-of-function mutations in FAM134B, encoding a newly identified cis
      Golgi protein, cause HSAN II. Fam134b knockdown results in structural alterations
      of the cis-Golgi compartment and induces apoptosis in some primary dorsal root
      ganglion neurons. This implicates FAM134B as critical in long-term survival of
      nociceptive and autonomic ganglion neurons.

PMID- 19838197
TI  - Transcriptional analysis of intracytoplasmically stained, FACS-purified cells by
      high-throughput, quantitative nuclease protection.
AB  - Analyzing specialized cells in heterogeneous tissues is crucial for understanding
      organ function in health and disease. Thus far, however, there has been no
      convenient method for studying gene expression in cells purified by fluorescence
      activated cell sorting (FACS) using intracellular markers. Here we show that the
      quantitative nuclease protection assay (qNPA) enables transcriptional analysis of
      intracytoplasmically stained cells sorted by FACS. Applying the method to mouse
      pancreatic islet-cell subsets, we detected both expected and unknown lineage
      specific gene expression patterns. Some beta cells from pregnant animals were
      found to express Mafb, previously observed only in immature beta cells during
      embryonic development. The four 'housekeeping' genes tested were expressed in
      purified islet-cell subpopulations with a notable variability, dependent on both
      cell lineage and developmental stage. Application of qNPA to intracellularly
      stained, FACS-sorted cells should be broadly applicable to the analysis of gene
      expression in subpopulations of any heterogeneous tissue, including tumors.

PMID- 19838198
TI  - Structural basis of receptor sharing by interleukin 17 cytokines.
AB  - Interleukin 17 (IL-17)-producing helper T cells (T(H)-17 cells), together with
      their effector cytokines, including members of the IL-17 family, are emerging as
      key mediators of chronic inflammatory and autoimmune disorders. Here we present
      the crystal structure of a complex of IL-17 receptor A (IL-17RA) bound to IL-17F
      in a 1:2 stoichiometry. The mechanism of complex formation was unique for
      cytokines and involved the engagement of IL-17 by two fibronectin-type domains of
      IL-17RA in a groove between the IL-17 homodimer interface. Binding of the first
      receptor to the IL-17 cytokines modulated the affinity and specificity of the
      second receptor-binding event, thereby promoting heterodimeric versus homodimeric
      complex formation. IL-17RA used a common recognition strategy to bind to several
      members of the IL-17 family, which allows it to potentially act as a shared
      receptor in multiple different signaling complexes.

PMID- 19838199
TI  - MicroRNA miR-326 regulates TH-17 differentiation and is associated with the
      pathogenesis of multiple sclerosis.
AB  - Interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) are increasingly
      recognized as key participants in various autoimmune diseases, including multiple
      sclerosis. Although sets of transcription factors and cytokines are known to
      regulate T(H)-17 differentiation, the role of noncoding RNA is poorly understood.
      Here we identify a T(H)-17 cell-associated microRNA, miR-326, whose expression
      was highly correlated with disease severity in patients with multiple sclerosis
      and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing
      of miR-326 resulted in fewer T(H)-17 cells and mild EAE, and its overexpression
      led to more T(H)-17 cells and severe EAE. We also found that miR-326 promoted
      T(H)-17 differentiation by targeting Ets-1, a negative regulator of T(H)-17
      differentiation. Our data show a critical role for microRNA in T(H)-17
      differentiation and the pathogenesis of multiple sclerosis.

PMID- 19838200
TI  - Defective survival of naive CD8+ T lymphocytes in the absence of the beta3
      regulatory subunit of voltage-gated calcium channels.
AB  - The survival of T lymphocytes requires sustained, Ca(2+) influx-dependent gene
      expression. The molecular mechanism that governs sustained Ca(2+) influx in naive
      T lymphocytes is unknown. Here we report an essential role for the beta3
      regulatory subunit of voltage-gated calcium (Ca(v)) channels in the maintenance
      of naive CD8(+) T cells. Deficiency in beta3 resulted in a profound survival
      defect of CD8(+) T cells. This defect correlated with depletion of the pore
      forming subunit Ca(v)1.4 and attenuation of T cell antigen receptor (TCR)
      mediated global Ca(2+) entry in CD8(+) T cells. Ca(v)1.4 and beta3 associated
      with T cell signaling machinery and Ca(v)1.4 localized in lipid rafts. Our data
      demonstrate a mechanism by which Ca(2+) entry is controlled by a Ca(v)1.4-beta3
      channel complex in T cells.

PMID- 19838201
TI  - Foxo1 integrates insulin signaling with mitochondrial function in the liver.
AB  - Type 2 diabetes is a complex disease that is marked by the dysfunction of glucose
      and lipid metabolism. Hepatic insulin resistance is especially pathogenic in type
      2 diabetes, as it dysregulates fasting and postprandial glucose tolerance and
      promotes systemic dyslipidemia and nonalcoholic fatty liver disease.
      Mitochondrial dysfunction is closely associated with insulin resistance and might
      contribute to the progression of diabetes. Here we used previously generated mice
      with hepatic insulin resistance owing to the deletion of the genes encoding
      insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double
      knockout (DKO) mice) to establish the molecular link between dysregulated insulin
      action and mitochondrial function. The expression of several forkhead box O1
      (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1
      (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers
      the NAD(+)/NADH ratio and ATP production. Although peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (Ppargc-1alpha) was also upregulated
      in DKO liver, it was acetylated and failed to promote compensatory mitochondrial
      biogenesis or function. Deletion of hepatic Foxo1 in DKO liver normalized the
      expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1alpha acetylation
      and restored mitochondrial oxidative metabolism and biogenesis. Thus, Foxo1
      integrates insulin signaling with mitochondrial function, and inhibition of Foxo1
      can improve hepatic metabolism during insulin resistance and the metabolic
      syndrome.

PMID- 19838202
TI  - PPAR-delta senses and orchestrates clearance of apoptotic cells to promote
      tolerance.
AB  - Macrophages rapidly engulf apoptotic cells to limit the release of noxious
      cellular contents and to restrict autoimmune responses against self antigens.
      Although factors participating in recognition and engulfment of apoptotic cells
      have been identified, the transcriptional basis for the sensing and the silent
      disposal of apoptotic cells is unknown. Here we show that peroxisome proliferator
      activated receptor-delta (PPAR-delta) is induced when macrophages engulf
      apoptotic cells and functions as a transcriptional sensor of dying cells. Genetic
      deletion of PPAR-delta decreases expression of opsonins such as complement
      component-1qb (C1qb), resulting in impairment of apoptotic cell clearance and
      reduction in anti-inflammatory cytokine production. This increases autoantibody
      production and predisposes global and macrophage-specific Ppard(-/-) mice to
      autoimmune kidney disease, a phenotype resembling the human disease systemic
      lupus erythematosus. Thus, PPAR-delta has a pivotal role in orchestrating the
      timely disposal of apoptotic cells by macrophages, ensuring that tolerance to
      self is maintained.

PMID- 19838203
TI  - The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the
      biosynthetic enzyme CqsA.
AB  - Vibrio cholerae, the bacterium that causes the disease cholera, controls
      virulence factor production and biofilm development in response to two
      extracellular quorum-sensing molecules, called autoinducers. The strongest
      autoinducer, called CAI-1 (for cholera autoinducer-1), was previously identified
      as (S)-3-hydroxytridecan-4-one. Biosynthesis of CAI-1 requires the enzyme CqsA.
      Here, we determine the CqsA reaction mechanism, identify the CqsA substrates as
      (S)-2-aminobutyrate and decanoyl coenzyme A, and demonstrate that the product of
      the reaction is 3-aminotridecan-4-one, dubbed amino-CAI-1. CqsA produces amino
      CAI-1 by a pyridoxal phosphate-dependent acyl-CoA transferase reaction. Amino-CAI
      1 is converted to CAI-1 in a subsequent step via a CqsA-independent mechanism.
      Consistent with this, we find cells release > or =100 times more CAI-1 than amino
      CAI-1. Nonetheless, V. cholerae responds to amino-CAI-1 as well as CAI-1, whereas
      other CAI-1 variants do not elicit a quorum-sensing response. Thus, both CAI-1
      and amino-CAI-1 have potential as lead molecules in the development of an
      anticholera treatment.

PMID- 19838204
TI  - Coupling DNA unwinding activity with primer synthesis in the bacteriophage T4
      primosome.
AB  - The unwinding and priming activities of the bacteriophage T4 primosome, which
      consists of a hexameric helicase (gp41) translocating 5' to 3' and an oligomeric
      primase (gp61) synthesizing primers 5' to 3', have been investigated on DNA
      hairpins manipulated by a magnetic trap. We find that the T4 primosome
      continuously unwinds the DNA duplex while allowing for primer synthesis through a
      primosome disassembly mechanism or a new DNA looping mechanism. A fused gp61-gp41
      primosome unwinds and primes DNA exclusively via the DNA looping mechanism. Other
      proteins within the replisome control the partitioning of these two mechanisms by
      disfavoring primosome disassembly, thereby increasing primase processivity. In
      contrast to T4, priming in bacteriophage T7 and Escherichia coli involves
      discrete pausing of the primosome and dissociation of the primase from the
      helicase, respectively. Thus nature appears to use several strategies to couple
      the disparate helicase and primase activities within primosomes.

PMID- 19838205
TI  - Roles of PKC isoforms in the induction of apoptosis elicited by aberrant Ras.
AB  - Emerging evidence indicates that suppression of protein kinase C (PKC) renders
      the susceptibility of cells expressing mutated ras to apoptosis. Although the
      effort has been made, the underlying molecular mechanisms are not fully
      understood. In this study, using small hairpin RNAs (shRNAs) or PKC inhibitor, we
      show that the concurrent suppression of PKC-alpha and beta induces cells
      ectopically expressing v-ras to undergo apoptosis. In this apoptotic process, PKC
      delta is upregulated and translocated from the cytosol to the nucleus. The
      activated PKC-delta associates with and phosphorylates p73 to initiate apoptosis.
      In this apoptotic process, Akt seems to be downstream of oncogenic Ras. Moreover,
      overexpression of PKC-delta, without co-suppression of PKC-alpha and beta, is not
      apoptotic to the cells, suggesting that PKC-delta and PKC-alpha/beta function
      oppositely to facilitate cells harboring v-ras to survive. Thus, our study shows
      that PKC-alpha and beta are necessary for sustaining the homeostasis in cells
      containing a hyperactive Ras. The abrogation of these two isoforms switches on
      the p73-regulated apoptotic machinery through the activation of PKC-delta.

PMID- 19838206
TI  - The Rap GTPases regulate the migration, invasiveness and in vivo dissemination of
      B-cell lymphomas.
AB  - B-cell lymphomas are common malignancies in which transformed B cells enter the
      circulation, extravasate into tissues and form tumors in multiple organs.
      Lymphoma cells are thought to exit the vasculature and enter tissues through the
      same chemokine- and adhesion molecule-dependent mechanisms as normal B cells. We
      have previously shown that activation of the Rap GTPases, proteins that control
      cytoskeletal organization and integrin activation, is critical for chemokine
      induced migration and adhesion in B-lymphoma cell lines. Using the A20 murine B
      lymphoma cell line as a model, we now show that Rap activation is important for
      circulating lymphoma cells to enter tissues and form tumors in vivo. In vitro
      assays showed that Rap activation is required for A20 cells to efficiently adhere
      to vascular endothelial cells and undergo transendothelial migration. These
      findings suggest that Rap or its effectors could be novel targets for treating B
      cell lymphomas.

PMID- 19838207
TI  - Transglutaminase 2 suppresses apoptosis by modulating caspase 3 and NF-kappaB
      activity in hypoxic tumor cells.
AB  - The expression of hypoxia-inducible factor-1 (HIF-1) correlates with poor
      clinical outcomes and confers resistance to the apoptosis of the tumor cells that
      are exposed to hypoxia. Presently, the mechanism underlying this phenomenon is
      poorly understood. In this study we provide evidence that transglutaminase 2
      (TG2), an enzyme that catalyses protein crosslinking reactions, is a
      transcriptional target of HIF-1 to enhance the survival of hypoxic cells. We
      found that hypoxia induces TG2 expression through an HIF-1 dependent pathway and
      concurrently activates intracellular TG2. The hypoxic cells overexpressing TG2
      showed resistance to apoptosis. Conversely, the hypoxic cells treated with either
      TG2 inhibitor or small interfering RNA (siRNA) became sensitive to apoptosis.
      Activation of TG2 in response to hypoxic stress inhibited caspase-3 activity by
      forming crosslinked multimer, resulting in insoluble aggregates. TG2 also
      activates nuclear factor (NF)-kappaB pathway after hypoxic stress, and thereby
      induces the expression of cellular inhibitor of apoptosis 2. The anti-apoptotic
      role of TG2 was further confirmed in vivo using xenografts in athymic mice. Our
      results indicate that TG2 is an anti-apoptotic mediator of HIF-1 through
      modulating both apoptosis and survival pathways and may confer a selective growth
      advantage to tumor cells. These findings suggest that the inhibition of TG2 may
      offer a novel strategy for anticancer therapy.

PMID- 19838208
TI  - The GAB2 signaling scaffold promotes anchorage independence and drives a
      transcriptional response associated with metastatic progression of breast cancer.
AB  - Acquisition of independence from anchorage to the extracellular matrix is a
      critical event for onset and progression of solid cancers. To identify and
      characterize new genes conferring anchorage independence, we transduced MCF10A
      human normal breast cells with a retroviral cDNA expression library and selected
      them by growth in suspension. Microarray analysis targeted on library-derived
      transcripts revealed robust and reproducible enrichment, after selection, of
      cDNAs encoding the scaffolding adaptor Gab2. Gab2 was confirmed to strongly
      promote anchorage-independent growth when overexpressed. Interestingly,
      downregulation by RNA interference of endogenous Gab2 in neoplastic cells did not
      affect their adherent growth, but abrogated their growth in soft agar. Gab2
      driven anchorage independence was found to specifically involve activation of the
      Src-Stat3 signaling axis. A transcriptional 'signature' of 205 genes was obtained
      from GAB2-transduced, anchorage-independent MCF10A cells, and found to contain
      two main functional modules, controlling proliferation and cell
      adhesion/migration/invasion, respectively. Extensive validation on breast cancer
      data sets showed that the GAB2 signature provides a robust prognostic classifier
      for breast cancer metastatic relapse, largely independent from existing clinical
      and genomic indicators and from estrogen receptor status. This work highlights a
      pivotal role for GAB2 and its transcriptional targets in anchorage-independent
      growth and breast cancer metastatic progression.

PMID- 19838209
TI  - The type I insulin-like growth factor receptor regulates cancer metastasis
      independently of primary tumor growth by promoting invasion and survival.
AB  - The type I insulin-like growth factor receptor (IGF1R) regulates multiple aspects
      of malignancy and is the target of several drugs currently in clinical trials.
      Although the function of IGF1R in proliferation and survival is well studied, the
      regulation of metastasis by IGF1R is not as clearly delineated. Previous work
      showed that disruption of IGF1R signaling by overexpression of a dominant
      negative IGF1R inhibited metastasis. To establish a clinically applicable
      approach to inhibition of metastasis by targeting IGF1R, we examined the effect
      of an inhibitory antibody against IGF1R, EM164 and its humanized version,
      AVE1642, on metastasis of cancer cells. EM164 and AVE1642 did not affect primary
      tumor growth of MDA-435A/LCC6 cells but inhibited metastasis of these cells.
      Consistent with this inhibition in the formation of metastatic nodules,
      disruption of IGF1R also resulted in a decreased number of circulating tumor
      cells in blood of tumor-bearing mice. Disruption of IGF1R with a dominant
      negative construct or antibody inhibited invasion across Matrigel in vitro. When
      tumor cells were directly injected into the circulation through the lateral tail
      vein of mice, IGF1R disruption also resulted in significant reduction of
      pulmonary nodules, suggesting that regulation of invasion is not the only
      function of IGF1R signaling. Further, disruption of IGF1R rendered cells more
      susceptible to anoikis. Thus, IGF1R regulated metastasis independently of tumor
      growth. The multiple phenotypes regulated by IGF1R must be considered during
      development of this therapeutic strategy as inhibition of metastasis independent
      of inhibition of tumor growth is not easily assessed in phase II clinical trials.

PMID- 19838210
TI  - Notch-1 activates estrogen receptor-alpha-dependent transcription via IKKalpha in
      breast cancer cells.
AB  - Approximately 80% of breast cancers express the estrogen receptor-alpha (ERalpha)
      and are treated with anti-estrogens. Resistance to these agents is a major cause
      of mortality. We have shown that estrogen inhibits Notch, whereas anti-estrogens
      or estrogen withdrawal activate Notch signaling. Combined inhibition of Notch and
      estrogen signaling has synergistic effects in ERalpha-positive breast cancer
      models. However, the mechanisms whereby Notch-1 promotes the growth of ERalpha
      positive breast cancer cells are unknown. Here, we demonstrate that Notch-1
      increases the transcription of ERalpha-responsive genes in the presence or
      absence of estrogen via a novel chromatin crosstalk mechanism. Our data support a
      model in which Notch-1 can activate the transcription of ERalpha-target genes via
      IKKalpha-dependent cooperative chromatin recruitment of Notch-CSL-MAML1
      transcriptional complexes (NTC) and ERalpha, which promotes the recruitment of
      p300. CSL binding elements frequently occur in close proximity to estrogen
      responsive elements (EREs) in the human and mouse genomes. Our observations
      suggest that a hitherto unknown Notch-1/ERalpha chromatin crosstalk mediates
      Notch signaling effects in ERalpha-positive breast cancer cells and contributes
      to regulate the transcriptional functions of ERalpha itself.

PMID- 19838211
TI  - MdmX is a substrate for the deubiquitinating enzyme USP2a.
AB  - It has previously been shown that ubiquitin-specific protease 2a (USP2a) is a
      regulator of the Mdm2/p53 pathway. USP2a binds to Mdm2 and can deubiquitinate
      Mdm2 without reversing Mdm2-mediated p53 ubiquitination. Overexpression of USP2a
      causes accumulation of Mdm2 and promotes p53 degradation. We now show that MdmX
      is also a substrate for USP2a. MdmX associates with USP2a independently of Mdm2.
      Ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2
      mediated degradation of MdmX. This correlates with the ability of wild-type USP2a
      to deubiquitinate MdmX. siRNA-mediated knockdown of USP2a in NTERA-2 testicular
      embryonal carcinoma cells and MCF7 breast cancer cells causes destabilization of
      MdmX and results in a decrease in MdmX protein levels, showing that endogenous
      USP2a participates in the regulation of MdmX stability. The therapeutic drug,
      cisplatin decreases MdmX protein expression. USP2a mRNA and protein levels were
      also reduced after cisplatin exposure. The magnitude and time course of USP2a
      downregulation suggests that the reduction in USP2a levels could contribute to
      the decrease in MdmX expression following treatment with cisplatin. Knockdown of
      USP2a increases the sensitivity of NTERA-2 cells to cisplatin, raising the
      possibility that suppression of USP2a in combination with cisplatin may be an
      approach for cancer therapy.

PMID- 19838212
TI  - DNA damage induces Chk1-dependent threonine-160 phosphorylation and activation of
      Cdk2.
AB  - Abnormal centrosome numbers arise in tumours and can cause multipolar mitoses and
      genome instability. Cdk2 controls normal centrosome duplication, but Chk1
      dependent centrosome amplification also occurs after DNA damage. We investigated
      the involvement of cyclin-dependent kinases (Cdks) in DNA damage-induced
      centrosome amplification using cells lacking either Cdk2, or both Cdk1 and Cdk2
      activity. Cdk2(-/-) DT40 cells showed robust centrosome amplification after
      ionizing radiation (IR), whereas Cdk1-deficient Cdk2(-/-) cells showed no
      centrosome amplification, demonstrating that Cdk1 can substitute for Cdk2 in this
      pathway. Surprisingly, we found that Cdk2 activity was upregulated by IR in wild
      type but not in Chk1(-/-) DT40 cells. Cdk2 upregulation also occurred in HeLa
      cells after IR treatment. Chk1-dependent Cdk2 induction was not accompanied by
      increased levels of Cdk1, Cdk2, cyclin A or cyclin E, but activating T160
      phosphorylation of Cdk2 increased after IR. Moreover, Cdk2 overexpression
      restored IR-induced centrosome amplification in Cdk1-deficient Cdk2(-/-) cells,
      but T160A mutation blocked this rescue. Our data suggest that Chk1 signalling
      causes centrosome amplification after IR by upregulating Cdk2 activity through
      activating phosphorylation.

PMID- 19838214
TI  - Genotoxic stress-induced nuclear localization of oncoprotein YB-1 in the absence
      of proteolytic processing.
AB  - Y-box-binding protein 1 (YB-1) is an oncogenic transcription factor whose
      overexpression and nuclear localization is associated with tumor progression and
      drug resistance. Transcriptional activation of YB-1 in response to genotoxic
      stress is believed to occur in the cytoplasm through sequence-specific
      endoproteolytic cleavage by the 20S Proteasome, followed by nuclear translocation
      of cleaved YB-1. To study the proteolysis model, we developed a two-step affinity
      purification of endogenous YB-1 protein species and characterized the products
      using mass spectrometry. Whereas full-length YB-1 was readily identified, the
      smaller protein band thought to be activated YB-1 was identified as hnRNP A1. An
      antibody specific for YB-1 was generated, which revealed only one YB-1 species,
      even after genotoxic stress-induced nuclear YB-1 translocation. These findings
      warrant re-evaluation of the mechanism of YB-1 nuclear translocation and
      transcriptional activation. The relationship between nuclear YB-1 and tumor
      progression may also have to re-evaluated in some cases.

PMID- 19838213
TI  - RB has a critical role in mediating the in vivo checkpoint response, mitigating
      secondary DNA damage and suppressing liver tumorigenesis initiated by aflatoxin
      B1.
AB  - Hepatocellular carcinoma (HCC) is a significant worldwide health concern that is
      associated with discrete etiological events, encompassing viral infection,
      metabolic stress and genotoxic compounds. In particular, exposure to the
      genotoxic hepatocarcinogen aflatoxin B1 (AFB1) is a significant factor in the
      genesis of human liver cancer. Presumably, genetic events associated with HCC
      could influence the effect of environmental insults, yielding a predilection for
      tumor development. The retinoblastoma (RB) tumor suppressor pathway is
      functionally inactivated in HCC through discrete mechanisms; however, the role of
      RB in suppressing tumorigenesis in this disease is poorly understood. Therefore,
      we analysed how RB status affects the response to AFB1 in reference to acute
      exposures and tumor development reflective of chronic exposure. Liver-specific Rb
      deletion resulted in an aberrant proliferative response to AFB1. This cell-cycle
      induction was associated with increased levels of secondary genetic damage and
      failure in appropriate cell-cycle coupling. This effect of RB loss was unique to
      AFB1 and involved the induction of a non-canonical proliferative pathway, and was
      not merely reflective of the overall cell-cycle deregulation or aberrant
      regenerative responses. The acute responses to AFB1 exposure presaged aberrations
      in hepatocyte nuclear morphology and ploidy with RB loss. Correspondingly, RB
      deficient livers showed significantly enhanced susceptibility to liver
      tumorigenesis initiated by AFB1. Combined, these studies show that RB has a
      critical role in mediating checkpoint responses in liver tissue to maintain
      genome integrity and in suppressing tumorigenesis.

PMID- 19838216
TI  - Knockdown of protein tyrosine phosphatase SHP-1 inhibits G1/S progression in
      prostate cancer cells through the regulation of components of the cell-cycle
      machinery.
AB  - SHP-1, a haematopoietic cell-specific tyrosine phosphatase, is also expressed in
      human prostate. In this study, we report that SHP-1 depletion in PC-3 cells
      induced by small interfering RNAs causes G1 phase cell-cycle arrest accompanied
      by changes in some components of the cell-cycle machinery. SHP-1 knockdown
      increases p27(Kip1) (p27) protein stability, its nuclear localization and p27
      gene transcription. These effects could be mediated by PI3K-AKT pathway as SHP-1
      interacts with PI3K regulating its activity and p110 catalytic subunit
      phosphorylation. The increase in p27 protein stability could also because of
      reduced cyclin-dependent kinase (CDK2) activity. SHP-1 knockdown decreases the
      CDK6 levels, inducing retinoblastoma protein hypophosphorylation, downregulation
      of cyclin E and thereby a decrease in the CDK2 activity. However, the codepletion
      of SHP-1 and p27 does not produce re-entry into the cycle, implying that p27 is
      not required to maintain cell-cycle arrest induced by SHP-1 depletion. The
      maintenance of the PC-3 cell anti-proliferative response after p27 loss could be
      because of mislocalization of CDK2 induced by SHP-1 knockdown. This study shows
      that SHP-1 depletion promotes cell-cycle arrest by modulating the activity of
      cell-cycle regulators and suggests that SHP-1 may be required for the proper
      functioning of events governing cell-cycle progression.

PMID- 19838215
TI  - Differential requirement of CAAX-mediated posttranslational processing for Rheb
      localization and signaling.
AB  - The Rheb1 and Rheb2 small GTPases and their effector mTOR are aberrantly
      activated in human cancer and are attractive targets for anti-cancer drug
      discovery. Rheb is targeted to endomembranes via its C-terminal CAAX (C=cysteine,
      A=aliphatic, X=terminal amino acid) motif, a substrate for posttranslational
      modification by a farnesyl isoprenoid. After farnesylation, Rheb undergoes two
      additional CAAX-signaled processing steps, Ras converting enzyme 1 (Rce1)
      catalyzed cleavage of the AAX residues and isoprenylcysteine carboxyl
      methyltransferase (Icmt)-mediated carboxylmethylation of the farnesylated
      cysteine. However, whether these postprenylation processing steps are required
      for Rheb signaling through mTOR is not known. We found that Rheb1 and Rheb2
      localize primarily to the endoplasmic reticulum and Golgi apparatus. We
      determined that Icmt and Rce1 processing is required for Rheb localization, but
      is dispensable for Rheb-induced activation of the mTOR substrate p70 S6 kinase
      (S6K). Finally, we evaluated whether farnesylthiosalicylic acid (FTS) blocks Rheb
      localization and function. Surprisingly, FTS prevented S6K activation induced by
      a constitutively active mTOR mutant, indicating that FTS inhibits mTOR at a level
      downstream of Rheb. We conclude that inhibitors of Icmt and Rce1 will not block
      Rheb function, but FTS could be a promising treatment for Rheb- and mTOR
      dependent cancers.

PMID- 19838217
TI  - Cells deficient in the base excision repair protein, DNA polymerase beta, are
      hypersensitive to oxaliplatin chemotherapy.
AB  - A significant proportion of human cancers overexpress DNA polymerase beta (Pol
      beta), the major DNA polymerase involved in base excision repair. The underlying
      mechanism and biological consequences of overexpression of this protein are
      unknown. We examined whether Pol beta, expressed at levels found in tumor cells,
      is involved in the repair of DNA damage induced by oxaliplatin treatment and
      whether the expression status of this protein alters the sensitivity of cells to
      oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon
      cancer cells was observed to be associated with the stabilization of Pol beta
      protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic
      oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive
      levels of Pol beta protein, faster in vitro repair of a DNA substrate containing
      a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in
      cells. In HCT-OR cells, small interfering RNA knockdown of Pol beta delayed the
      repair of oxaliplatin-induced DNA damage. In a different model system, Pol beta
      deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and
      were hypersensitive to oxaliplatin treatment compared with isogenic Pol beta
      expressing cells. Consistent with previous studies, Pol beta-deficient mouse
      fibroblasts were not hypersensitive to cisplatin treatment. These data provide
      the first link between oxaliplatin sensitivity and DNA repair involving Pol beta.
      They demonstrate that Pol beta modulates the sensitivity of cells to oxaliplatin
      treatment.

PMID- 19838219
TI  - Comparative assessment of telomere length before and after hematopoietic SCT:
      role of grafted cells in determining post-transplant telomere status.
AB  - Our objective was to characterize the role of grafted cells in determining
      telomere length (TL) after hematopoietic SCT (HSCT). A total of 20 patients
      undergoing autografts had PBSC collected after two sequential mobilization
      courses: TL in the first collection was significantly longer than in the second.
      For their autografts, 10 patients used PBSC from the first collection and 10 from
      the second. TL was also investigated before and after HSCT and on the graft in 10
      allogeneic HSCT. After autografting, patients receiving PBSC from the first
      collection had BM TL reflecting that of grafted cells (median bp: 7730 on PBSC vs
      7610 on post-HSCT BM, P=NS) and significantly longer than TL of the second
      collection; analogously, patients autografted with PBSC from the second
      collection had BM TL reflecting that of grafted cells (7360 on PBSC vs 7120 on
      post-HSCT BM, P=NS) and significantly shorter compared with the first collection.
      In the allograft setting, eight patients had their pre-transplant TL
      significantly shorter than donor PBSC (5960 vs 7110; P=0.0005); following HSCT,
      BM TL (median 7380 bp) was identical to that of the graft (P=NS). We conclude
      that grafted cells have a major role in determining TL after HSCT.

PMID- 19838218
TI  - The Ron receptor tyrosine kinase positively regulates angiogenic chemokine
      production in prostate cancer cells.
AB  - Overexpression of the Ron receptor tyrosine kinase has recently been shown in a
      wide variety of human cancers. However, no studies have examined Ron receptor
      expression or function during prostate tumorigenesis. In this study we report
      that Ron is highly expressed in human prostate adenocarcinoma and metastatic
      lymph nodes when compared with normal prostate or benign prostate hyperplasia.
      Furthermore, we show that Ron is overexpressed in PC-3 and DU145 prostate cancer
      cell lines, and that the levels of angiogenic chemokines produced by prostate
      cancer cells positively correlate with Ron expression. The knockdown of Ron in PC
      3 or DU145 cells results in a significant decrease in angiogenic chemokine
      production and is associated with a decreased activation of the transcription
      factor nuclear factor-kappaB (NF-kappaB). Moreover, exogenous overexpression of
      Ron in LNCaP cells is sufficient to induce a significant increase in angiogenic
      chemokines that can be abrogated by inhibition of NF-kappaB signaling. Given that
      the function of angiogenic chemokines is important in the development of new
      blood vessels, we also examined the ability of Ron to modulate endothelial cell
      migration. Our data show that knockdown of Ron in prostate cancer cells results
      in significantly less endothelial cell chemotaxis when compared with Ron
      expressing cells in vitro as well as in reduced tumor growth and decreased
      microvessel density after orthotopic transplantation into the prostate in vivo.
      In total, our data suggest that the Ron receptor is important in modulating
      prostate tumor growth by modulating angiogenic chemokine production and
      subsequent endothelial cell recruitment.

PMID- 19838221
TI  - Miniature circular polarization analyzer with spiral plasmonic lens.
AB  - A simple spiral plasmonic lens is studied both analytically and numerically.
      Owing to the geometric phase effect, a spiral plasmonic lens focuses the left
      hand and right-hand circular polarizations into spatially separated plasmonic
      fields. Such a spatial multiplexing of the field distribution is utilized in
      miniature circular polarization analyzer design. A circular polarization
      extinction ratio better than 100 is obtainable with a device size as small as
      4lambda(spp). The spiral plasmonic lens provides efficient plasmonic focusing
      while it eliminates the requirement of centering the incident beam to the
      plasmonic lens, making it suitable for full Stokes parameter polarimetric imaging
      applications.

PMID- 19838220
TI  - CD3(+) and/or CD14(+) depletion from cord blood mononuclear cells before ex vivo
      expansion culture improves total nucleated cell and CD34(+) cell yields.
AB  - Cord blood (CB) is used increasingly in transplant patients lacking sibling or
      unrelated donors. A major hurdle in the use of CB is its low cell dose, which is
      largely responsible for an elevated risk of graft failure and a significantly
      delayed neutrophil and platelet engraftment. As a positive correlation has been
      shown between the total nucleated cell (TNC) and CD34(+) cell dose transplanted
      and time to neutrophil and platelet engraftment, strategies to increase these
      measures are under development. One strategy includes the ex vivo expansion of CB
      mononuclear cells (MNC) with MSC in a cytokine cocktail. We show that this
      strategy can be further improved if CD3(+) and/or CD14(+) cells are first
      depleted from the CB MNC before ex vivo expansion. Ready translation of this
      depletion strategy to improve ex vivo CB expansion in the clinic is feasible as
      clinical-grade devices and reagents are available. Ultimately, the aim of
      improving TNC and CD34(+) transplant doses is to further improve the rate of
      neutrophil and platelet engraftment in CB recipients.

PMID- 19838222
TI  - Stable transmission of radio frequency signals on fiber links using
      interferometric delay sensing.
AB  - We demonstrate distribution of a 2850 MHz rf signal over stabilized optical fiber
      links. For a 2.2 km link we measure an rms drift of 19.4 fs over 60 h, and for a
      200 m link an rms drift of 8.4 fs over 20 h. The rf signals are transmitted as
      amplitude modulation on a continuous optical carrier. Variations in the delay
      length are sensed using heterodyne interferometry and used to correct the rf
      phase. The system uses standard fiber telecommunications components.

PMID- 19838223
TI  - Noncritical singly resonant synchronously pumped OPO for generation of picosecond
      pulses in the mid-infrared near 6.4 microm.
AB  - The recently developed chalcopyrite CdSiP(2) is employed in a picosecond, 90
      degrees -phase-matched, synchronously pumped, optical parametric oscillator
      pumped at 1064 nm to produce steady-state idler pulses near 6.4 microm with an
      energy as high as 2.8 microJ at 100 MHz, in a train of 2-micros-long macropulses
      following at a repetition rate of 25 Hz. Without an intracavity etalon, the 12.6
      ps-long micropulses have a spectral width of 240 GHz.

PMID- 19838224
TI  - Kerr-lens mode-locked femtosecond Cr(2+):ZnSe laser at 2420 nm.
AB  - We describe a cw Kerr-lens mode-locked Cr(2+):ZnSe laser pumped by a 1800 nm
      thulium fiber laser. The astigmatically compensated asymmetric x cavity contained
      a 2.4-mm-long Cr(2+):ZnSe sample with a pump absorption coefficient of 11.6 cm(
      1) and was operated with a 1% output coupler. The dispersion compensation was
      achieved by using a MgF(2) prism pair. During Kerr-lens mode-locked operation, we
      could generate 95 fs pulses at a pulse repetition rate of 94.3 MHz and with 40 mW
      of output power. The center wavelength of the pulses was 2420 nm. The pulses had
      a spectral width of 69 nm and a time-bandwidth product of 0.335, which is close
      to the transform limit for hyperbolic secant pulses.

PMID- 19838225
TI  - Coexistence of polarization-locked and polarization-rotating vector solitons in a
      fiber laser with SESAM.
AB  - We report the experimental observation of the coexistence of polarization-locked
      vector solitons (PLVSs) and polarization-rotating vector solitons (PRVSs) in a
      fiber laser mode locked with a semiconductor saturable absorber mirror. It was
      found experimentally that interaction between the PLVSs in a fiber laser could
      lead to formation of bound states of PRVSs. Moreover, the bound PRVSs as a unit
      have the same group velocity as that of the PLVSs in the cavity.

PMID- 19838226
TI  - Liquid-cooled 24 W mid-infrared Er:ZBLAN fiber laser.
AB  - A 24 W liquid-cooled CW 3 microm fiber laser with a multimode-core Er-doped ZBLAN
      fiber has been developed. The output power of 24 W and an optical-to-optical
      efficiency of 14.5% (with respect to incident pump power) were obtained with 975
      nm diode pumping. Efficient cooling was implemented by a combination of fluid
      cooling over the entire length of the fiber and conductive cooling at both end
      faces of the fiber. Consequently, stable high-power operation was demonstrated.
      To our knowledge, this is the highest output power obtained by a 3 microm fiber
      laser. Furthermore, the high power can be further scaled up, since the output
      power in the present work is limited only by the available pump power.

PMID- 19838227
TI  - Ultrasensitive direct-field retrieval of femtosecond pulses by modified
      interferometric field autocorrelation.
AB  - We report on spectral phase retrieval of 50 MHz, 374 fs optical pulses at 1560 nm
      with 28 aJ coupled pulse energy by measuring two modified interferometric field
      autocorrelation traces using a 5-cm-long periodically poled lithium niobate
      waveguide. The corresponding sensitivity is 1.1x10(-7) mW(2), improving on the
      previous record by about 20 times. The same data traces can also be used to
      retrieve the power spectrum, given that the ratio of powers at two specific
      wavelengths is known.

PMID- 19838229
TI  - Faraday dichroic beam splitter for Raman light using an isotopically pure alkali
      metal-vapor cell.
AB  - We present an application of the Faraday effect to produce a narrowband dichroic
      beam splitter using an alkali metal vapor. Two Raman beams detuned in frequency
      by the ground-state hyperfine splitting in (87)Rb are produced using an electro
      optic modulator and then separated using the Faraday effect in an isotopically
      pure (85)Rb thermal vapor. An experimental transmission spectra for the beam
      splitter is presented along with a theoretical calculation. The performance of
      the beam splitter is then demonstrated and characterized using a Fabry-Perot
      etalon. For a temperature of 70 degrees C and a longitudinal magnetic field of 80
      G, a suppression of one frequency of 18 dB is achieved, limited by the quality of
      the polarizers.

PMID- 19838228
TI  - Toward a 1550 nm InGaAs photoconductive switch for terahertz generation.
AB  - We report a terahertz (THz) photoconductive switch made from a composite of metal
      ErAs nanoparticles embedded in In(0.53)Ga(0.47)As and coupled to a square spiral
      antenna. The THz output power was measured in a 77 K cryostat by using a standard
      hyperhemisphere-lens package, a Golay cell outside the cryostat, and a quasi
      optical filter bank for spot frequency spectral measurements. Results indicate an
      average output power of approximately 12 microW at 22 V bias using 140 mW of
      optical pump power from a subpicosecond fiber mode-locked laser. In addition, the
      THz spectra displayed invariance to bias voltage despite operating near impact
      ionization.

PMID- 19838230
TI  - Two-point Stokes parameters: interpretation and properties.
AB  - Whereas the classic Stokes parameters are measures of intensity, the recently
      introduced two-point Stokes parameters characterize spatial coherence. It is
      shown that in analogy to the Stokes parameters, the two-point parameters have a
      physical interpretation as sums and differences of (scalar) cross-spectral
      density functions of specific electric-field components. A measurement scheme and
      several physical consequences of the two-point parameters are discussed.

PMID- 19838231
TI  - Carbon nanotube-doped polymer optical fiber.
AB  - We present a method to fabricate graded-index multimode polymer optical fibers
      doped with carbon nanotubes (CNTs). Such fiber structures provide the means to
      fully utilize the exceptional optical properties of the CNTs. The core region of
      the fiber is composed of CNTs and polymethyl methacrylate (PMMA) with the
      addition of diphenyl sulfide (DPS), which acts as the dispersion stabilizer of
      CNTs in PMMA as well as the dopant to increase the refractive index of the core.
      Utilizing 2.5 cm of the fiber as a saturable absorber, passively mode-locked
      lasing with duration of 3.0 ps and repetition rate of 30.3 MHz was demonstrated.

PMID- 19838232
TI  - Flexible 3-D shape measurement using projector defocusing.
AB  - We present a 3-D shape-measurement technique using a defocused projector. The
      ideal sinusoidal fringe patterns are generated by defocusing binary structured
      patterns, and the phase shift is realized by shifting the binary patterns
      spatially. Because this technique does not require calibration of the gamma of
      the projector, it is easy to implement and thus is promising for developing
      flexible 3-D shape measurement systems using digital video projectors.

PMID- 19838233
TI  - Control of supercontinuum generation and soliton self-frequency shift in solid
      core photonic bandgap fibers.
AB  - We experimentally investigate the nonlinear propagation of subnanosecond pulses
      in solid-core photonic bandgap fibers. By launching pulses with a few kilowatts
      peak power, a flat supercontinuum is generated. The long-wavelength edge of the
      supercontinuum can be controlled thanks to the original linear properties
      inherent to solid-core photonic bandgap fibers. This allows one to tailor the
      generated supercontinuum radiation and to keep it over a given spectral range of
      interest without any significant power loss.

PMID- 19838234
TI  - Depth-resolved microscopy of cortical hemodynamics with optical coherence
      tomography.
AB  - We describe depth-resolved microscopy of cortical hemodynamics with high-speed
      spectral/Fourier domain optical coherence tomography (OCT). Stimulus-evoked
      changes in blood vessel diameter, flow, and total hemoglobin were measured in the
      rat somatosensory cortex. The results show OCT measurements of hemodynamic
      changes during functional activation and represent an important step toward
      understanding functional hyperemia at the microscopic level.

PMID- 19838235
TI  - Characteristics of a waveguide mode in a trilayer Ag/SiO(2)/Au plasmonic thermal
      emitter.
AB  - A suitably designed trilayer Ag/SiO(2)/Au thermal emitter can be used as the
      narrow bandwidth infrared light source. The thermal radiation generated in the
      SiO(2) layer resonates between the two metal films and results in not only the
      Ag/SiO(2) surface plasmon polaritons but also the waveguide mode (WM) in the
      Ag/SiO(2)/Au structure owing to the thick SiO(2) layer. This study investigated
      the influence of dielectric thickness on energy dispersion relations and derived
      the theoretical dispersion relation, which fit well with experimental results.
      This WM light source can be applied in the area of gas sensing and probing the
      response of the animal cells and plants to infrared radiation.

PMID- 19838236
TI  - Optical ultra-wide-band pulse bipolar and shape modulation based on a symmetric
      PM-IM conversion architecture.
AB  - A simple and feasible technique for ultra-wide-band (UWB) pulse bipolar
      modulation (PBM) and pulse shape modulation (PSM) in the optical domain is
      proposed and demonstrated. The PBM and PSM are performed using a symmetric phase
      modulation to intensity modulation conversion architecture, including a couple of
      phase modulators and an optical bandpass filter (OBPF). Two optical carriers,
      which are separately phase modulated by two appropriate electrical pulse
      patterns, are at the long- and short-wavelength linear slopes of the OBPF
      spectrum, respectively. The high-speed PBM and PSM without limit of chip length,
      polarity, and shape are implemented in simulation and are also verified by
      experiment.

PMID- 19838237
TI  - Multifunctional photoreactive inorganic cages for three-dimensional holographic
      data storage.
AB  - We demonstrate a holographic photopolymer based on multifunctional photoreactive
      inorganic cages, polyhedral oligomeric silsesquioxane (POSS). It is shown that a
      second photopolymerizable monomer, POSS, for the photopolymer, contributes to
      significantly enhance photosensitivity as well as refractive index modulation
      (Deltan). We also found that during the formation of holographic gratings,
      polymerization of POSS could effectively suppress volume shrinkage of
      photopolymer resin, owing to its filler-strengthening effect of inorganic cages
      accompanied with interpenetrating effect.

PMID- 19838238
TI  - Blind sectional image reconstruction for optical scanning holography.
AB  - Optical scanning holography is a powerful holographic recording technique in
      which only a single two-dimensional scan is needed to record three-dimensional
      information. As in standard digital holography, for the reconstruction of a
      sectional image, the resulting data must then be postprocessed to obtain
      sectional content. We propose a blind sectional image reconstruction technique to
      automate the data processing. This reconstruction uses edge information to
      determine the appropriate Fresnel zone plates automatically and applies inverse
      imaging to recover the sectional images with significant suppression of the
      defocus noise. The experimental data used to verify the algorithm are measured
      from a physical implementation of the optical scanning holography system.

PMID- 19838239
TI  - Simultaneous readout of positive and negative images for dc-removed coaxial
      holographic data storage.
AB  - A method of reconstructing positive and negative images simultaneously from the
      same dc-removed coaxial Fourier hologram with the same reference pattern is
      presented. The simultaneous reconstruction is possible by making the polarization
      of the additional dc component of the signal beam perpendicular to the
      polarization of the reconstructed signal beam, in which separately detected s-
      and p-polarization components create contrast-reversed images. This method
      provides an aspect of designing dc-removed coaxial holographic storage systems
      for realizing optical noise reduction and less consumption of dynamic range of
      the recording medium.

PMID- 19838240
TI  - Long-distance soliton transmission through ultralong fiber lasers.
AB  - We present the first experimental demonstration (to our knowledge) of long
      distance unperturbed fundamental optical soliton transmission in conventional
      single-mode optical fiber. The virtual transparency in the fiber required for
      soliton transmission, over 15 complete periods, was achieved by using an
      ultralong Raman fiber laser amplification scheme. Optical soliton pulse duration,
      pulse bandwidth, and peak intensity are shown to remain constant along the
      transmission length. Frequency-resolved optical gating spectrograms and numerical
      simulations confirm the observed optical soliton dynamics.

PMID- 19838241
TI  - Absolute frequency stabilization of an extended-cavity diode laser against
      Doppler-free H(2)O17 absorption lines at 1.384 microm.
AB  - We report the frequency stabilization of a cw extended-cavity diode laser against
      saturated absorption lines of the H(2)O17 isotopologue of water vapor at around
      1.384 microm. The saturation of rotovibrational transitions is achieved by
      filling a high-finesse optical resonator with H(2)O17 at low pressure and by
      locking the laser frequency to the resonator by using the Pound-Drever-Hall
      technique. Absolute frequency stabilization is obtained, locking the cavity
      resonance to the center of the sub-Doppler line by means of the wavelength
      modulation method. A relative frequency stability of sigma(y)(tau)=10(
      13)(0.1tau(-2)+0.9)(1/2) is demonstrated for integration times in the range 4
      ms<tau<30 s.

PMID- 19838242
TI  - Wide-field high-resolution surface-plasmon interference microscopy.
AB  - We describe a wide-field interferometric surface-plasmon microscope capable of
      submicrometer resolution. The system is a speckle-illuminated Linnik
      interferometer, which behaves as a wide-field analog of a scanning heterodyne
      interferometer. The presented images demonstrate contrast reversals at different
      defocus while retaining submicrometer lateral resolution. The contrast mechanisms
      are discussed as well as the instrumental requirements of the technique.

PMID- 19838243
TI  - Pulse propagation in a fiber Bragg grating written in a slow saturable fiber
      amplifier.
AB  - We have developed a model to study nonlinear pulse propagation in a fiber Bragg
      grating written in an erbium-doped fiber amplifier. The saturation effect in such
      amplifiers depends on the accumulated energy along the pulse rather than on the
      pulse instantaneous power. We have shown that the gain saturation effect cannot
      be neglected when Bragg solitons are amplified by erbium-doped fiber amplifiers.
      The slow saturation of the amplifier limits the output pulse power, and it tends
      to split the amplified pulse into several pulses. We have shown that when the
      propagation velocity of the amplified pulses decreases, the amplifier gain per
      unit length increases.

PMID- 19838244
TI  - Terahertz-bandwidth high-order temporal differentiators based on phase-shifted
      long-period fiber gratings.
AB  - We report the fabrication of a pi-phase-shifted long-period fiber grating (LPFG)
      capable of operating as a terahertz-bandwidth second-order temporal
      differentiator. We demonstrate its operation experimentally by differentiating
      subpicosecond long optical pulses. A new scheme for achieving high-order photonic
      temporal differentiation based on LPFG filters is also proposed and demonstrated.
      In particular, we prepared a LPFG-based first-order differentiator that was
      frequency and bandwidth matched to the second-order device and demonstrated the
      cascadability of these devices leading to the implementation of a third-order
      differentiator. By also employing these devices in reflection, up to the fifth
      order differentiation is demonstrated experimentally.

PMID- 19838245
TI  - Single-polarization operation in birefringent all-solid hybrid microstructured
      fiber with additional stress applying parts.
AB  - We demonstrate single-polarization (SP) operation in a birefringent all-solid
      hybrid microstructured fiber that has additional boron-doped stress-applying
      parts (SAPs). The stress from the SAPs is added to the stress from the highly
      germanium-doped high-index regions, and SP operation with more than a 25 nm
      bandwidth was achieved at the shorter wavelength edge of the second bandgap.

PMID- 19838246
TI  - Gas mixing analysis by simultaneous Raman imaging and particle image velocimetry.
AB  - We report the combined application of Ramanography and particle image velocimetry
      (PIV) for the investigation of gas mixing processes. A droplet seeded hydrogen
      flow was injected as a free jet into pressurized nitrogen at 0.95 MPa.
      Ramanography and PIV were used to quantitatively image the mixture composition
      and the flow field of the mixing process, respectively.

PMID- 19838247
TI  - Efficient continuum generation exceeding 200 eV by intense ultrashort two-color
      driver.
AB  - A temporal gating on the high-order harmonic emission process is achieved using
      an intense 20 fs, 1.45 microm pulse (IR) in combination with an intense 13 fs,
      800 nm pulse [visible (VIS)]. Exploiting this two-color gating scheme, a coherent
      continuous emission extending up to 160 eV using Ar gas and 200 eV using Ne gas
      is efficiently generated. The IR pulse contributes to significantly extending the
      harmonic emission to higher photon energies, whereas the VIS pulse improves the
      conversion efficiency of the process. These results indicate the possibility to
      produce bright attosecond pulses approaching the soft X spectral region.

PMID- 19838248
TI  - Designing the Fourier space with transformation optics.
AB  - We show that transformation optics can be applied to extend the functionalities
      of conventional optical devices. In particular, geometrically compressing the
      input facet of any conventional optical elements can extend the input spatial
      frequency bandwidth. As an example, we design a Fourier lens that can transform
      the image to its reciprocal space and operate for incident light of subwavelength
      profile. An explicit design employing metal-dielectric layers is given for
      realization.

PMID- 19838249
TI  - Single-frequency 1 W hybrid Brillouin/ytterbium fiber laser.
AB  - A high-power hybrid Brillouin/ytterbium fiber laser has been demonstrated with an
      output power of 1 W. The laser operates in the single-frequency regime with an
      optical signal-to-noise ratio greater than 55 dB in a 0.1 nm bandwidth.

PMID- 19838250
TI  - Simple and fast calculation algorithm for computer-generated hologram with
      wavefront recording plane.
AB  - We present a simple and fast calculation algorithm for a computer-generated
      hologram (CGH) by use of wavefront recording plane. The wavefront recording plane
      is placed between the object data and a CGH. When the wavefront recording plane
      is placed close to the object, the object light passes through a small region on
      the wave recording plane. The computational complexity for the object light is
      very small. We can obtain a CGH to execute diffraction calculation from the
      wavefront recording plane to the CGH. The computational complexity is constant.
      The total computational complexity is dramatically reduced in comparison with
      conventional CGH calculations.

PMID- 19838251
TI  - Millimeter-wave radio-over-fiber system based on two-step heterodyne technique.
AB  - We theoretically demonstrate an improved two-step-heterodyne-based, millimeter
      wave, radio-over-fiber system. With the millimeter-wave mixer and a fiber Bragg
      grating located in the base station, two-step heterodyne is achieved. The
      proposed scheme has the merit of good system performance and high suppression of
      unwanted frequency tones, which is verified by numerical simulations.

PMID- 19838252
TI  - Power-scalable 1.57 microm mode-locked semiconductor disk laser using wafer
      fusion.
AB  - We report the first (to our knowledge) wafer-fused high-power passively mode
      locked semiconductor disk laser operating at 1.57 microm wavelength. An InP-based
      active medium was fused with GaAs/AlGaAs distributed Bragg reflector on a 2 inch
      wafer level, resulting in an integrated monolithic gain mirror. An intracavity
      wedged diamond heat-spreader capillary bonded to the gain chip provides efficient
      heat removal from the gain structure without disturbing the spectrum of the mode
      locked laser. The laser produces over 0.6 W of average output power at 15 degrees
      C with 16 ps pulse width. The total output power accounting for all output beams
      emerging from the cavity was 0.86 W. The results reveal an essential advantage of
      wafer fusion processing of disparate materials over monolithically grown InP
      based gain structures and demonstrate the high potential of this technique for
      power scaling of long-wavelength semiconductor disk lasers.

PMID- 19838253
TI  - Effects of oxide formation around core circumference of silicon-on-oxidized
      porous-silicon strip waveguides.
AB  - We have studied the effect of oxidation on the propagation loss and surface
      roughness of silicon-on-oxidized-porous-silicon strip waveguides fabricated using
      proton-beam irradiation and electrochemical etching. A thin thermal oxide is
      formed around the core of the waveguide, enabling the symmetric reduction of core
      size and roughness on all sides. Significant loss reduction from about 10 dB/cm
      to 1 dB/cm has been obtained in TE and TM polarizations after oxidation
      smoothening of both the bottom and the sidewalls by 20 nm. This corresponds well
      with simulations using the beam-propagation method that show significant
      contributions from both surfaces.

PMID- 19838254
TI  - Dynamic aberration correction for multiharmonic microscopy.
AB  - We demonstrate image-based aberration correction in a third-harmonic generation
      (THG) microscope. We describe a robust, mostly sample-independent correction
      scheme relying on prior measurement of the influence of aberration modes produced
      by a deformable mirror on the quality of THG images. We find that using image
      sharpness as an image quality metric, correction of N aberration modes is
      achieved using 2(2N+1) measurements in a variety of samples. We also report
      aberration correction in combined multiharmonic and two-photon excited
      fluorescence experiments. Finally, we demonstrate time-dependent adaptive THG
      imaging in developing embryonic tissue.

PMID- 19838255
TI  - Laser reflectometry of submegahertz liquid meniscus ringing.
AB  - Optical techniques that permit nondestructive probing of interfacial dynamics of
      various media are of key importance in numerous applications such as
      ellipsometry, mirage effect, and all-optical switching. Characterization of the
      various phases of microjet droplet formation yields important information for
      volume control, uniformity, velocity, and rate. The ringing of the meniscus and
      the associated relaxation time that occurs after droplet breakoff affect
      subsequent drop formation and is an indicator of the physical properties of the
      fluid. Using laser reflectometry, we present an analysis of the meniscus
      oscillations in an orifice of a piezoelectric microjet.

PMID- 19838256
TI  - Adaptive window Wigner-Ville-distribution-based method to estimate phase
      derivative from optical fringes.
AB  - We introduce an adaptive window Wigner-Ville-distribution-based method to
      directly estimate the phase derivative from a single fringe pattern. In the
      proposed method, the phase derivative is estimated by using the peak detection of
      the pseudo-Wigner-Ville distribution for a set of different window lengths. Then
      the optimal window length is selected from the set by resolving the estimator's
      bias variance trade-off, using the intersection of confidence intervals rule.
      Finally, the phase derivative estimate corresponding to the optimum window is
      selected. Simulation and experimental results are presented to demonstrate the
      method's applicability for the phase derivative estimation.

PMID- 19838257
TI  - Adaptive harmonic generation microscopy of mammalian embryos.
AB  - Adaptive optics is implemented in a harmonic generation microscope using a
      wavefront sensorless correction scheme. Both the second- and third-harmonic
      intensity signals are used as the optimization metric. Aberration correction is
      performed to compensate both system- and specimen-induced aberrations by using an
      efficient optimization routine based upon Zernike polynomial modes. Images of
      live mouse embryos show an improved signal level and resolution.

PMID- 19838258
TI  - Measurements of spectral broadening and Doppler shift of backreflections from a
      fiber fuse using heterodyne detection.
AB  - We report broadening in spectrum as light is backreflected from a propagating
      fiber fuse. The formation of micrometer-size voids results in periodic changes in
      Fresnel reflection occurring in the leading part of the fuse. High-resolution
      measurement of the optical spectrum via heterodyne detection revealed an upshift
      (Doppler shift) in the optical frequency and discrete frequency components that
      are characteristic of amplitude modulation due to periodic void formation.

PMID- 19838259
TI  - Nonparaxial polarizers.
AB  - We develop a theoretical description for polarizers that goes beyond the paraxial
      approximation. By combining existing theories for fields with nonplanar
      wavefronts, we are able to derive a simple power series expansion expressing the
      electric field of a light beam after a polarizer as a linear function of the
      field and its spatial derivatives evaluated before the polarizer. The first few
      terms of such expansion are explicitly given, and their physical meaning is
      discussed.

PMID- 19838260
TI  - Surface nanoprocessing with nondiffracting femtosecond Bessel beams.
AB  - We demonstrate the application of nondiffracting Bessel beams for reproducible
      nanometric-scale feature patterning in glass. A femtosecond pulse zero-order
      Bessel beam with a central spot radius of 360 nm was used to write 500 nm radius
      nanocraters over a longitudinal positioning range exceeding 20 microm, with a
      variation in radius of less than 10%. The use of Bessel beams significantly
      reduces constraints on critical sample positioning in the nanoscale writing
      regime, enabling the use of femtosecond pulses for fast inscription of nanometer
      scale features over large sample areas.

PMID- 19838261
TI  - Radially polarized annular beam generated through a second-harmonic-generation
      process.
AB  - A radially polarized beam with an annular intensity pattern was generated through
      a second-harmonic-generation process by focusing an azimuthally polarized
      Ti:sapphire pulsed laser beam to a c-cut beta-barium borate (BBO) crystal. The
      annular intensity pattern of the second-harmonic wave had a nearly sixfold
      symmetry as a result of the nonlinear susceptibility tensor of the BBO crystal.
      The width of the annulus was as narrow as less than 1/40th of its radius.

PMID- 19838262
TI  - Ultranarrow bandwidth spectral filtering for long-range free-space quantum key
      distribution at daytime.
AB  - We describe a Fabry-Perot-based spectral filter for free-space quantum key
      distribution (QKD). A multipass etalon filter was built, and its performance was
      studied. The whole filter setup was carefully optimized to add less than 2 dB
      attenuation to a signal beam but block stray light by 21 dB. Simulations show
      that such a filter might be sufficient to allow QKD satellite downlinks during
      daytime with the current technology.

PMID- 19838263
TI  - m-bonacci metamaterial multilayers: location of the zero-average index bandgap
      edges.
AB  - We examine quasiperiodic multilayers arranged in m-bonacci sequences, which
      combine ordinary positive-index materials and dispersive metamaterials with
      negative index in a certain frequency range. When the volume-averaged refractive
      index of the nonperiodic multilayer equals zero, the structure does not propagate
      light radiation and exhibits a forbidden band. We identify some analytical
      expressions to determine the upper and lower limits of the above zero-average
      refractive-index bandgap. We recognize that these limits are not explicitly
      dependent on the geometrical parameters of the stack of layers.

PMID- 19838264
TI  - Impact of surface roughness on laser surface authentication signatures under
      linear and rotational displacements.
AB  - Laser surface authentication (LSA) is a technique for authenticating optically
      rough surfaces based on the intensity of diffusely scattered light. The
      degradation in the LSA signature over linear and rotational displacement is
      examined. Randomly roughened glass surfaces with roughness amplitudes ranging
      from 0.4 microm to 3 microm and correlation lengths from 16 microm to 45 microm
      are examined experimentally, showing that the average size of the surface feature
      has a negligible impact on the rate of LSA signature degradation. The average
      size of the surface features is shown to have a greater effect on the fractional
      intensity of the variations in diffuse light and on the quality of LSA signature
      match.

PMID- 19838265
TI  - Interferometric quasi-absolute tests for aspherics using a radial shear position.
AB  - Increasing accuracy requirements in aspheric metrology make the development of
      absolute testing procedures for aspheric surfaces important. One strategy is
      transferring the standard practice three-position test for spheres to aspherics.
      The three-position test, however, involves a cat's eye position and therefore has
      certain drawbacks. We propose an absolute testing method for rotationally
      symmetric aspherics where the cat's eye position is replaced with a radially
      sheared position. Together with rotational movements of the specimen, the surface
      deviations can be obtained in an absolute manner. To demonstrate the validity of
      the procedure, we present a measurement result for a sphere and compare it with a
      result obtained by the standard three-position test.

PMID- 19838266
TI  - High quantum efficiency of near-infrared emission in bismuth doped AlGeP-silica
      fiber.
AB  - A self-calibrating method is described for measuring the radiative quantum
      efficiency (QE) in doped optical fibers. The method uses an integrating sphere to
      collect the fluorescence from the fiber, with pump light transmitted through the
      fiber end serving as a reference. QE measurements for a 780 or 808 nm pump were
      made on bismuth-doped AlGeP-silica fibers prepared by aerosol deposition. For
      both wavelengths, a value of QE=1.0+/-0.05 was obtained. Fluorescence was
      observed in two bands centered around 800 and 1300 nm, and the relative strength
      of these bands was found to vary with the pump wavelength.

PMID- 19838267
TI  - Experimental demonstration of a suspended diffractively coupled optical cavity.
AB  - All-reflective optical systems are under consideration for future gravitational
      wave detector topologies. One approach in proposed designs is to use diffraction
      gratings as input couplers for Fabry-Perot cavities. We present an experimental
      demonstration of a fully suspended diffractively coupled cavity and investigate
      the use of conventional Pound-Drever-Hall length sensing and control techniques
      to maintain the required operating condition.

PMID- 19838268
TI  - Total elimination of sampling errors in polarization imagery obtained with
      integrated microgrid polarimeters.
AB  - Microgrid polarimeters operate by integrating a focal plane array with an array
      of micropolarizers. The Stokes parameters are estimated by comparing polarization
      measurements from pixels in a neighborhood around the point of interest. The main
      drawback is that the measurements used to estimate the Stokes vector are made at
      different locations, leading to a false polarization signature owing to
      instantaneous field-of-view (IFOV) errors. We demonstrate for the first time, to
      our knowledge, that spatially band limited polarization images can be ideally
      reconstructed with no IFOV error by using a linear system framework.

PMID- 19838269
TI  - Determination of the phase of terahertz few-cycle laser pulses.
AB  - We propose an approach to determine the carrier-envelope phase (CEP) of a
      terahertz few-cycle pulse by observing the field-free molecular orientation. We
      find that the degree of orientation sensitively depends on the CEP, providing a
      new route for measuring the CEP without phase ambiguity. By taking advantage of
      the field-free molecular orientation, an important effect of the CEP drift caused
      by the dephasing of the generating medium on the accurate measurement of the CEP
      value is eliminated.

PMID- 19838270
TI  - Wavelength-tunable few-cycle optical pulses directly from an all-fiber Er-doped
      laser setup.
AB  - A simple design, which we believe to be the first of its kind, of an all-fiber
      based optical source is proposed for the generation of widely tunable few-cycle
      pulses as short as 20-25 fs duration in the range of 1.6-2.1 microm. Few-cycle
      pulses are obtained by compression of femtosecond pulses from the erbium-doped
      fiber laser in a three-stage scheme that uses (i) the effects of the soliton
      compression and the Raman frequency tuning in the dispersion decreasing fiber, as
      well as (ii) supercontinuum generation in a high-nonlinear silica fiber, and
      (iii) subsequent compression in a short conventional fiber.

PMID- 19838272
TI  - Subdiffraction propagation of images using saturated absorption of optical
      transition.
AB  - We show how well-developed saturated absorption spectroscopy could be adopted for
      subdiffraction propagation of optical images. We employ pump beams with
      appropriate spatial profiles that produce controllable inhomogeneous absorption
      and dispersion of the medium. We discuss advantages of using super-Gaussian and
      Laguerre-Gaussian pump beams.

PMID- 19838271
TI  - Scanning fiber angle-resolved low coherence interferometry.
AB  - We present a fiber-optic probe for Fourier-domain angle-resolved low coherence
      interferometry for the determination of depth-resolved scatterer size. The probe
      employs a scanning single-mode fiber to collect the angular scattering
      distribution of the sample, which is analyzed using the Mie theory to obtain the
      average size of the scatterers. Depth sectioning is achieved with low coherence
      Mach-Zehnder interferometry. In the sample arm of the interferometer, a fixed
      fiber illuminates the sample through an imaging lens and a collection fiber
      samples the backscattered angular distribution by scanning across the Fourier
      plane image of the sample. We characterize the optical performance of the probe
      and demonstrate the ability to execute depth-resolved sizing with subwavelength
      accuracy by using a double-layer phantom containing two sizes of polystyrene
      microspheres.

PMID- 19838273
TI  - Ultraefficient control of light transmission through photonic potential barrier
      modulation.
AB  - An optical modulation mechanism based on dynamically shifting the photonic
      potential barrier of a photonic crystal waveguide is presented. The modulation
      mechanism is modeled by the one-dimensional quantum tunneling effect using the
      Schrodinger equation. The calculation results show that the modulation efficiency
      is 200 times higher than that of the conventional Mach-Zehnder modulator. Based
      on this innovative concept, an engineering design of an ultracompact silicon
      photonic crystal waveguide modulator with 10 microm x 5 microm footprint is
      presented.

PMID- 19838274
TI  - Integrated acousto-optic polarization converter in a ZX-cut LiNbO(3) waveguide
      superlattice.
AB  - We report an integrated acousto-optic polarization converter exploiting a novel
      surface acoustic superlattice (S-ASL) transducer. The S-ASL transducer is made of
      a ZX-cut periodically poled lithium niobate (PPLN) crystal with uniform coplanar
      electrodes for surface acoustic wave (SAW) generation. For a PPLN period of 20
      microm the SAW is excited at an rf of about 190 MHz, while the phase matching
      occurs at an optical wavelength of around 1456 nm. The measured mode conversion
      efficiency of 90% at an input rf power of 1 W and the 3 dB optical bandwidth of
      2.5 nm confirm the confinement of the SAW between the electrode gap and the
      constructive interaction along the whole 10 mm electrode length.

PMID- 19838275
TI  - Strong fluorescence-signal gain with single-excitation-enhancing and emission
      directing nanostructured diffraction grating.
AB  - A dielectric subwavelength diffraction grating structure is designed and
      fabricated in order to enhance fluorescence-based detection of biomolecules. Two
      separate phenomena, enhancement of the local energy densities of the excitation
      illumination and direction of the emitted signal toward the detector, are
      examined theoretically and experimentally. 530-fold enhancement of detected
      signal is achieved compared with the signal from flat surface. Also, changes in
      polarization and coherence properties of the fluorescent light are found to be
      remarkable.

PMID- 19838276
TI  - Interaction of two parallel femtosecond filaments at different wavelengths in
      air.
AB  - We study the interaction of two parallel-launched femtosecond filaments at their
      fundamental-wave and second-harmonic frequencies in air. Besides the Kerr effect
      within the pulse duration, the impulsive alignment of the diatomic molecules in
      the fundamental-wave filament leads to controllable and field-free achievable
      attraction, fusion, or repulsion of the second-harmonic filament. The molecular
      alignment-assisted filament interaction is further confirmed by the fluorescence
      intensity variation and spectral modulation of the second-harmonic filament at
      various molecular alignment revivals.

PMID- 19838277
TI  - Bio-inspired accommodating fluidic intraocular lens.
AB  - The invention of intraocular lens (IOL), a substitute for crystalline lens,
      represents a major advancement in cataract surgery. After about sixty years of
      IOL development, one key remaining problem is its limited accommodation range
      compared with natural eyes. To overcome this performance limit, we explore bio
      inspired fluidic IOL. By mimicking the working principle of natural eyes, a
      fluidic intraocular lens can achieve an exceedingly large accommodation range. An
      experiment on fluidic IOL demonstrated a very high tuning range of 12 D. This
      accommodation range was achieved with a modest amount of force (0.06 N) and
      equatorial radius change (0.286 mm), in conditions matching well with the
      characteristics of aged eyes.

PMID- 19838278
TI  - Analysis of Brillouin frequency shift and acoustic waves in a hollow optical
      fiber.
AB  - We propose and demonstrate a new method to manipulate the Brillouin frequency
      shift in silica optical fiber by introducing a silica hollow optical fiber (HOF)
      waveguide structure. Propagation characteristics of acoustic waves guided along
      the HOF were theoretically analyzed, and the corresponding Brillouin frequency
      shifts were measured by a Brillouin optical-correlation domain-analysis system.
      We experimentally observed that Brillouin frequency shift v(B) monotonically
      increases as a function of the central air-hole radius, which showed good
      agreement with the simulation results. We confirmed that a precise control of
      Brillouin frequency shift can be obtained by controlling the waveguide parameters
      of the HOF.

PMID- 19838279
TI  - Autostereoscopic three-dimensional projector based on two parallax barriers.
AB  - An autostereoscopic 3D projector using several 2D projectors, a projection
      screen, and two parallax barriers is proposed. Parallax barrier 1 facing the 2D
      projectors collimates the images that have aberrations on the edge of the
      projection screen. Parallax barrier 2 facing viewers acts as the parallax barrier
      in ordinary autostereoscopic 3D displays. The operation principle of the system,
      the calculation equations for the parallax barriers, and the capture and
      correction of parallax images are described in detail. A 60-inch autostereoscopic
      3D projector prototype having four 2D projectors was developed. The presentation
      of 3D static, animation, and video images is realized by the prototype. The
      prototype's stereoscopic images without aberrations and with a little cross talk
      are sharp. Especially, its 3D resolution is the same as its 2D resolution.

PMID- 19838280
TI  - Optical image encryption topology.
AB  - Optical image encryption topology is proposed based on the principle of random
      phase encoding. Various encryption topological units, involving peer-to-peer,
      ring, star, and tree topologies, can be realized by an optical 6f system. These
      topological units can be interconnected to constitute an optical image encryption
      network. The encryption and decryption can be performed in both digital and
      optical methods.

PMID- 19838281
TI  - Suppression of perturbed free-induction decay and noise in experimental ultrafast
      pump-probe data.
AB  - We apply a Fourier filtering technique for the global removal of coherent
      contributions, like perturbed free-induction decay, and noise, to experimental
      pump-probe spectra. A further filtering scheme gains access to spectra otherwise
      only recordable by scanning the probe's center frequency with adjustable spectral
      resolution. These methods cleanse pump-probe data and allow improved
      visualization and simpler analysis of the contained dynamics. We demonstrate
      these filters using visible pump/mid-infrared probe spectroscopy of ligand
      dissociation in carboxyhemoglobin.

PMID- 19838282
TI  - Singular optical manipulation of birefringent elastic media using nonsingular
      beams.
AB  - It is shown that nonsingular light beams can generate singular birefringent
      patterns in homogeneous birefringent elastic media. These orientational defects
      of the optical-axis spatial distribution originate from an optical torque driven
      by a nonzero longitudinal field component. Singular radial and spin-dependent
      azimuthal light-induced elastic distortion patterns are described and
      experimentally observed in a uniform liquid-crystal film in the course of a
      focused circularly polarized Gaussian beam.

PMID- 19838283
TI  - Imaging of virtual objects with a plane periodic grating.
AB  - The purpose of this study is to let a plane periodic grating act as an imaging
      element for general objects. Using the Fresnel approximation and the Kirchhoff
      diffraction theory, we investigated an object wave diffracted by a grating. We
      demonstrated that an image of an original virtual object can be produced by the
      nth-order monochromatic diffracted wave of a grating. The impulse response of
      this imaging system and some imaging properties of this imaging system were
      obtained.

PMID- 19838284
TI  - Line-scanning reflectance confocal microscopy of human skin: comparison of full
      pupil and divided-pupil configurations.
AB  - Line-scanning, with pupil engineering and the use of linear array detectors, may
      enable simple, small, and low-cost confocal microscopes for clinical imaging of
      human epithelial tissues. However, a fundamental understanding of line-scanning
      performance within the highly scattering and aberrating conditions of human
      tissue is necessary, to translate from benchtop instrumentation to clinical
      implementation. The results of a preliminary investigation for reflectance
      imaging in skin are reported.

PMID- 19838285
TI  - Non-Poissonian statistics from Poissonian light sources with application to
      passive decoy state quantum key distribution.
AB  - We propose a method to prepare different non-Poissonian signal pulses from
      sources of Poissonian photon number distribution, using only linear optical
      elements and threshold photon detectors. This method allows a simple passive
      preparation of decoy states for quantum key distribution. We show that the
      resulting key rates are comparable with the performance of active choices of
      intensities of Poissonian signals.

PMID- 19838286
TI  - Estimation of the optical receiving plane positions of solar spectroradiometers
      with spherical diffusers on the basis of spatial responsivity data.
AB  - A straightforward method for estimating the position of the optical receiving
      plane of a spherical, dome-shaped diffuser from its spatial responsivity data is
      presented. The method is tested with two diffusers, types J1002 and J1015 from
      CMS Schreder, commonly used in solar UV spectroradiometers. The shift of the
      receiving plane from its nominal position determines a potential measurement
      error that occurs when measurements and calibrations are carried out with sources
      at different distances from the diffuser. Such information is particularly
      valuable for voluminous solar UV monitoring spectroradiometers that cannot easily
      be transported to laboratory calibrations. The results suggest that systematic
      measurement errors are at least of the order of 1%, if the position of the
      receiving plane is not properly taken into account, thus indicating a need to
      study the effect more carefully. This method can also be used to minimize
      measurement errors when designing diffusers.

PMID- 19838287
TI  - Nanostructured scintillating optical fiber prepared via sol-gel technique for
      detecting gamma radiation.
AB  - An innovative scintillating material prepared through distributing cesium iodide
      (CsI) nanocrystals into pores of a transparent nanoporous silica using a sol-gel
      technology has been developed. The CsI nanocrystals doped porous silica material
      has been designed and made into an optical fiber by using a patented sol-gel
      technique. This CsI-doped sol-gel silica optical fiber was conveniently connected
      to a highly sensitive photon detector in testing the material for detecting gamma
      radiation. The preliminary test result reported in this Letter clearly
      demonstrates the feasibility of this scintillating fiber for detecting high
      energy radiations.

PMID- 19838288
TI  - Effect of fractal rough-surface Hurst exponent on speckle in imaging systems.
AB  - Speckle image contrasts from a fractal rough-surface object are investigated in
      simulation, where the image surface is conjugate to the object surface. It is
      observed that the Hurst exponent H of fractal roughness affects speckle contrast
      and statistics dramatically. For example, a strong rough surface
      (sigma(h)>lambda) exhibits Rayleigh statistics over increasing ranges of point
      spread function widths as H decreases. Conceptual explanations are also presented
      for effects of H and the coherence factor on speckle in imaging systems.

PMID- 19838289
TI  - Role of Placebo Factors in Clinical Trials with Special Focus on Enrichment
      Designs.

PMID- 19838290
TI  - Coupling of Fischer carbene complexes with conjugated enediynes featuring radical
      traps; Novel structure and reactivity features of chromium complexed arene
      diradical species.
AB  - The reaction of Fischer carbene complexes with conjugated enediynes that feature
      a pendant alkene group has been examined. The reaction proceeds through carbene
      alkyne coupling to generate an enyne-ketene intermediate. This intermediate then
      undergoes Moore cyclization to generate a chromium complexed arene diradical,
      which then undergoes cyclization with the pendant alkene group. The radical
      cyclization prefers the 6-endo mode unless radical-stabilizing groups are present
      to favor the 5-exo mode. The intermediate diradical species were evaluated
      computationally in both the singlet and triplet configurations. Arene triplet
      diradicals feature minimal spin density at oxygen and delocalization to chromium.
      The 6-endo cyclization product was kinetically and thermodynamically favored.

PMID- 19838291
TI  - Polymerization Behavior and Polymer Properties of Eosin-Mediated Surface
      Modification Reactions.
AB  - Surface modification by surface-mediated polymerization necessitates control of
      the grafted polymer film thicknesses to achieve the desired property changes.
      Here, a microarray format is used to assess a range of reaction conditions and
      formulations rapidly in regards to the film thicknesses achieved and the
      polymerization behavior. Monomer formulations initiated by eosin conjugates with
      varying concentrations of poly(ethylene glycol) diacrylate (PEGDA), N
      methyldiethanolamine (MDEA), and 1-vinyl-2-pyrrolidone (VP) were evaluated.
      Acrylamide with MDEA or ascorbic acid as a coinitiator was also investigated. The
      best formulation was found to be 40 wt% acrylamide with MDEA which yielded four
      to eight fold thicker films (maximum polymer thickness increased from 180 nm to
      1420 nm) and generated visible films from 5-fold lower eosin surface densities
      (2.8 vs. 14 eosins/um(2)) compared to a corresponding PEGDA formulation. Using a
      microarray format to assess multiple initiator surface densities enabled facile
      identification of a monomer formulation that yields the desired polymer
      properties and polymerization behavior across the requisite range of initiator
      surface densities.

PMID- 19838292
TI  - Salvage of exposed breast implant using capsular flaps.
AB  - OBJECTIVE: Extrusion represents potential complications associated with the use
      of breast implants. Attempts to salvage the exposed implants are rarely
      successful when poor tissue coverage or radiotherpy is present and therefore
      removal of implant and wound healing are mandatory. In these refractory
      complicated cases the use of capsular flaps can represent a useful tool to save
      the implant and achieve definitive healing. METHODS: Capsular flaps have been
      performed on 6 patients with implant extrusion and 11 patients with breast
      contour deformities over the last 6 years. The authors describe an innovative
      technique using capsular flaps which are harvested from thicker viable tissues
      and inset in multiple layers into the fistula tract to reinforce the breast
      envelope and prevent recurrence of implant extrusion. RESULTS: Complete healing
      and implant salvage were achieved in all patients treated. No major complications
      occurred and only minor contour deformities, that regressed spontaneously after
      surgery, were observed for 2 weeks. CONCLUSIONS: Although capsular flaps have
      been previously described to correct breast shape deformities, no previous report
      has yet suggested its utility in breast implant salvage in case of extrusion. The
      authors advocate the use of capsular flap to save the exposed breast implant
      especially when poor tissue coverage is present and other surgical options to
      save the implant have already failed.

PMID- 19838293
TI  - One more piece in the VACV ecological puzzle: could peridomestic rodents be the
      link between wildlife and bovine vaccinia outbreaks in Brazil?
AB  - BACKGROUND: Despite the fact that smallpox eradication was declared by the World
      Health Organization (WHO) in 1980, other poxviruses have emerged and re-emerged,
      with significant public health and economic impacts. Vaccinia virus (VACV), a
      poxvirus used during the WHO smallpox vaccination campaign, has been involved in
      zoonotic infections in Brazilian rural areas (Bovine Vaccinia outbreaks - BV),
      affecting dairy cattle and milkers. Little is known about VACV's natural hosts
      and its epidemiological and ecological characteristics. Although VACV was
      isolated and/or serologically detected in Brazilian wild animals, the link
      between wildlife and farms has not yet been elucidated. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we describe for the first time, to our knowledge, the
      isolation of a VACV (Mariana virus - MARV) from a mouse during a BV outbreak.
      Genetic data, in association with biological assays, showed that this isolate was
      the same etiological agent causing exanthematic lesions observed in the cattle
      and human inhabitants of a particular BV-affected area. Phylogenetic analysis
      grouped MARV with other VACV isolated during BV outbreaks.
      CONCLUSION/SIGNIFICANCE: These data provide new biological and epidemiological
      information on VACV and lead to an interesting question: could peridomestic
      rodents be the link between wildlife and BV outbreaks?

PMID- 19838294
TI  - Exposure to p,p'-DDE: a risk factor for type 2 diabetes.
AB  - BACKGROUND: Persistent organic pollutants (POPs), such as PCBs, DDT and dioxins
      have in several cross-sectional studies shown strong associations with type 2
      diabetes mellitus. Reversed causality can however not be excluded. The aim of
      this case-control study was to evaluate whether POPs concentration is a risk
      factor for type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study
      was performed within a well-defined cohort of women, age 50-59 years, from the
      Southern part of Sweden. Biomarkers for POP exposure, 2,2',4,4',5,5'
      hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene
      (p,p'-DDE) were analyzed in stored serum samples, which were collected at the
      baseline examination when the cohort was established. For 107 out of the 371
      cases, serum samples were stored at least three years before their type 2
      diabetes was diagnosed. In this data set, CB-153 and p,p'-DDE were not associated
      with an increased risk to develop type 2 diabetes. However, when only the cases
      (n = 39) that were diagnosed more than six years after the baseline examination
      and their controls were studied, the women in the highest exposed quartile showed
      an increased risk to develop type 2 diabetes (OR of 1.6 [95% 0.61, 4.0] for CB
      153 and 5.5 [95% CI 1.2, 25] for p,p'-DDE). CONCLUSIONS/SIGNIFICANCE: The results
      from the present case-control study, including a follow-up design, confirms that
      p,p'-DDE exposure can be a risk factor for type 2 diabetes.

PMID- 19838295
TI  - Transcription analysis of central metabolism genes in Escherichia coli. Possible
      roles of sigma38 in their expression, as a response to carbon limitation.
AB  - The phosphoenolpyruvate: carbohydrate transferase system (PTS) transports glucose
      in Escherichia coli. Previous work demonstrated that strains lacking PTS, such as
      PB11, grow slow on glucose. PB11 has a reduced expression of glycolytic, and
      upregulates poxB and acs genes as compared to the parental strain JM101, when
      growing on glucose. The products of the latter genes are involved in the
      production of AcetylCoA. Inactivation of rpoS that codes for the RNA polymerase
      sigma(38) subunit, reduces further (50%) growth of PB11, indicating that
      sigma(38) plays a central role in the expression of central metabolism genes in
      slowly growing cells. In fact, transcription levels of glycolytic genes is
      reduced in strain PB11rpoS(-) as compared to PB11. In this report we studied the
      role of sigma(70) and sigma(38) in the expression of the complete glycolytic
      pathway and poxB and acs genes in certain PTS(-) strains and their rpoS(-)
      derivatives. We determined the transcription start sites (TSSs) and the
      corresponding promoters, in strains JM101, PB11, its derivative PB12 that
      recovered its growth capacity, and in their rpoS(-) derivatives, by 5'RACE and
      pyrosequencing. In all these genes the presence of sequences resembling sigma(38)
      recognition sites allowed the proposition that they could be transcribed by both
      sigma factors, from overlapping putative promoters that initiate transcription at
      the same site. Fourteen new TSSs were identified in seventeen genes. Besides,
      more than 30 putative promoters were proposed and we confirmed ten previously
      reported. In vitro transcription experiments support the functionality of
      putative dual promoters. Alternatives that could also explain lower transcription
      levels of the rpoS(-) derivatives are discussed. We propose that the presence if
      real, of both sigma(70) and sigma(38) dependent promoters in all glycolytic genes
      and operons could allow a differential transcription of these central metabolism
      genes by both sigma subunits as an adaptation response to carbon limitation.

PMID- 19838296
TI  - Characterization of the molecular determinants of primary HIV-1 Vpr proteins:
      impact of the Q65R and R77Q substitutions on Vpr functions.
AB  - Although HIV-1 Vpr displays several functions in vitro, limited information
      exists concerning their relevance during infection. Here, we characterized Vpr
      variants isolated from a rapid and a long-term non-progressor (LTNP).
      Interestingly, vpr alleles isolated from longitudinal samples of the LTNP
      revealed a dominant sequence that subsequently led to diversity similar to that
      observed in the progressor patient. Most of primary Vpr proteins accumulated at
      the nuclear envelope and interacted with host-cell partners of Vpr. They
      displayed cytostatic and proapoptotic activities, although a LTNP allele,
      harboring the Q65R substitution, failed to bind the DCAF1 subunit of the
      Cul4a/DDB1 E3 ligase and was inactive. This Q65R substitution correlated with
      impairment of Vpr docking at the nuclear envelope, raising the possibility of a
      functional link between this property and the Vpr cytostatic activity. In
      contradiction with published results, the R77Q substitution, found in LTNP
      alleles, did not influence Vpr proapoptotic activity.

PMID- 19838297
TI  - Analysis of blood stem cell activity and cystatin gene expression in a mouse
      model presenting a chromosomal deletion encompassing Csta and Stfa2l1.
AB  - The cystatin protein superfamily is characterized by the presence of conserved
      sequences that display cysteine protease inhibitory activity (e.g., towards
      cathepsins). Type 1 and 2 cystatins are encoded by 25 genes of which 23 are
      grouped in 2 clusters localized on mouse chromosomes 16 and 2. The expression and
      essential roles of most of these genes in mouse development and hematopoiesis
      remain poorly characterized. In this study, we describe a set of quantitative
      real-time PCR assays and a global expression profile of cystatin genes in normal
      mouse tissues. Benefiting from our collection of DelES embryonic stem cell clones
      harboring large chromosomal deletions (to be reported elsewhere), we selected a
      clone in which a 95-kb region of chromosome 16 is missing (Del(16qB3Delta/+)). In
      this particular clone, 2 cystatin genes, namely Csta and Stfa2l1 are absent along
      with 2 other genes (Fam162a, Ccdc58) and associated intergenic regions. From this
      line, we established a new homozygous mutant mouse model
      (Del(16qB3Delta/16qB3Delta)) to assess the in vivo biological functions of the 2
      deleted cystatins. Stfa2l1 gene expression is high in wild-type fetal liver, bone
      marrow, and spleen, while Csta is ubiquitously expressed. Homozygous
      Del(16qB3Delta/16qB3Delta) animals are phenotypically normal, fertile, and not
      overtly susceptible to spontaneous or irradiation-induced tumor formation. The
      hematopoietic stem and progenitor cell activity in these mutant mice are also
      normal. Interestingly, quantitative real-time PCR expression profiling reveals a
      marked increase in the expression levels of Stfa2l1/Csta phylogenetically-related
      genes (Stfa1, Stfa2, and Stfa3) in Del(16qB3Delta/16qB3Delta) hematopoietic
      tissues, suggesting that these candidate genes might be contributing to
      compensatory mechanisms. Overall, this study presents an optimized approach to
      globally monitor cystatin gene expression as well as a new mouse model deficient
      in Stfa2l1/Csta genes, expanding the available tools to dissect cystatin roles
      under normal and pathological conditions.

PMID- 19838298
TI  - Caspase-dependent inhibition of mousepox replication by gzmB.
AB  - BACKGROUND: Ectromelia virus is a natural mouse pathogen, causing mousepox. The
      cytotoxic T (Tc) cell granule serine-protease, granzyme B, is important for its
      control, but the underlying mechanism is unknown. Using ex vivo virus immune Tc
      cells, we have previously shown that granzyme B is able to activate several
      independent pro-apoptotic pathways, including those mediated by Bid/Bak/Bax and
      caspases-3/-7, in target cells pulsed with Tc cell determinants. METHODS AND
      FINDINGS: Here we analysed the physiological relevance of those pro-apoptotic
      pathways in ectromelia infection, by incubating ectromelia-immune ex vivo Tc
      cells from granzyme A deficient (GzmB(+) Tc cells) or granzyme A and granzyme B
      deficient (GzmAxB(-/-) Tc cell) mice with ectromelia-infected target cells. We
      found that gzmB-induced apoptosis was totally blocked in ectromelia infected or
      peptide pulsed cells lacking caspases-3/-7. However ectromelia inhibited only
      partially apoptosis in cells deficient for Bid/Bak/Bax and not at all when both
      pathways were operative suggesting that the virus is able to interfere with
      apoptosis induced by gzmB in case not all pathways are activated. Importantly,
      inhibition of viral replication in vitro, as seen with wild type cells, was not
      affected by the lack of Bid/Bak/Bax but was significantly reduced in caspase-3/-7
      deficient cells. Both caspase dependent processes were strictly dependent on
      gzmB, since Tc cells, lacking both gzms, neither induced apoptosis nor reduced
      viral titers. SIGNIFICANCE: Out findings present the first evidence on the
      biological importance of the independent gzmB-inducible pro-apoptotic pathways in
      a physiological relevant virus infection model.

PMID- 19838299
TI  - DAZL relieves miRNA-mediated repression of germline mRNAs by controlling poly(A)
      tail length in zebrafish.
AB  - BACKGROUND: During zebrafish embryogenesis, microRNA (miRNA) miR-430 contributes
      to restrict Nanos1 and TDRD7 to primordial germ cells (PGCs) by inducing mRNA
      deadenylation, mRNA degradation, and translational repression of nanos1 and tdrd7
      mRNAs in somatic cells. The nanos1 and tdrd7 3'UTRs include cis-acting elements
      that allow activity in PGCs even in the presence of miRNA-mediated repression.
      METHODOLOGY/PRINCIPAL FINDINGS: Using a GFP reporter mRNA that was fused with
      tdrd7 3'UTR, we show that a germline-specific RNA-binding protein DAZ-like (DAZL)
      can relieve the miR-430-mediated repression of tdrd7 mRNA by inducing poly(A)
      tail elongation (polyadenylation) in zebrafish. We also show that DAZL enhances
      protein synthesis via the 3'UTR of dazl mRNA, another germline mRNA targeted by
      miR-430. CONCLUSIONS/SIGNIFICANCE: Our present study indicated that DAZL acts as
      an "anti-miRNA factor" during vertebrate germ cell development. Our data also
      suggested that miRNA-mediated regulation can be modulated on specific target
      mRNAs through the poly(A) tail control.

PMID- 19838300
TI  - An intergenic non-coding rRNA correlated with expression of the rRNA and
      frequency of an rRNA single nucleotide polymorphism in lung cancer cells.
AB  - BACKGROUND: Ribosomal RNA (rRNA) is a central regulator of cell growth and may
      control cancer development. A cis noncoding rRNA (nc-rRNA) upstream from the 45S
      rRNA transcription start site has recently been implicated in control of rRNA
      transcription in mouse fibroblasts. We investigated whether a similar nc-rRNA
      might be expressed in human cancer epithelial cells, and related to any genomic
      characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Using quantitative rRNA
      measurement, we demonstrated that a nc-rRNA is transcribed in human lung
      epithelial and lung cancer cells, starting from approximately -1000 nucleotides
      upstream of the rRNA transcription start site (+1) and extending at least to
      +203. This nc-rRNA was significantly more abundant in the majority of lung cancer
      cell lines, relative to a nontransformed lung epithelial cell line. Its abundance
      correlated negatively with total 45S rRNA in 12 of 13 cell lines (P = 0.014).
      During sequence analysis from -388 to +306, we observed diverse, frequent
      intercopy single nucleotide polymorphisms (SNPs) in rRNA, with a frequency
      greater than predicted by chance at 12 sites. A SNP at +139 (U/C) in the 5'
      leader sequence varied among the cell lines and correlated negatively with level
      of the nc-rRNA (P = 0.014). Modelling of the secondary structure of the rRNA 5'
      leader sequence indicated a small increase in structural stability due to the
      +139 U/C SNP and a minor shift in local configuration occurrences.
      CONCLUSIONS/SIGNIFICANCE: The results demonstrate occurrence of a sense nc-rRNA
      in human lung epithelial and cancer cells, and imply a role in regulation of the
      rRNA gene, which may be affected by a +139 SNP in the 5' leader sequence of the
      primary rRNA transcript.

PMID- 19838301
TI  - Noninvasive, in vivo assessment of mouse retinal structure using optical
      coherence tomography.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a novel method of retinal in
      vivo imaging. In this study, we assessed the potential of OCT to yield histology
      analogue sections in mouse models of retinal degeneration. METHODOLOGY/PRINCIPAL
      FINDINGS: We achieved to adapt a commercial 3(rd) generation OCT system to obtain
      and quantify high-resolution morphological sections of the mouse retina which so
      far required in vitro histology. OCT and histology were compared in models with
      developmental defects, light damage, and inherited retinal degenerations. In
      conditional knockout mice deficient in retinal retinoblastoma protein Rb, the
      gradient of Cre expression from center to periphery, leading to a gradual
      reduction of retinal thickness, was clearly visible and well topographically
      quantifiable. In Nrl knockout mice, the layer involvement in the formation of
      rosette-like structures was similarly clear as in histology. OCT examination of
      focal light damage, well demarcated by the autofluorescence pattern, revealed a
      practically complete loss of photoreceptors with preservation of inner retinal
      layers, but also more subtle changes like edema formation. In Crb1 knockout mice
      (a model for Leber's congenital amaurosis), retinal vessels slipping through the
      outer nuclear layer towards the retinal pigment epithelium (RPE) due to the lack
      of adhesion in the subapical region of the photoreceptor inner segments could be
      well identified. CONCLUSIONS/SIGNIFICANCE: We found that with the OCT we were
      able to detect and analyze a wide range of mouse retinal pathology, and the
      results compared well to histological sections. In addition, the technique allows
      to follow individual animals over time, thereby reducing the numbers of study
      animals needed, and to assess dynamic processes like edema formation. The results
      clearly indicate that OCT has the potential to revolutionize the future design of
      respective short- and long-term studies, as well as the preclinical assessment of
      therapeutic strategies.

PMID- 19838302
TI  - Genetic enhancement of memory and long-term potentiation but not CA1 long-term
      depression in NR2B transgenic rats.
AB  - One major theory in learning and memory posits that the NR2B gene is a universal
      genetic factor that acts as rate-limiting molecule in controlling the optimal
      NMDA receptor's coincidence-detection property and subsequent learning and memory
      function across multiple animal species. If so, can memory function be enhanced
      via transgenic overexpression of NR2B in another species other than the
      previously reported mouse species? To examine these crucial issues, we generated
      transgenic rats in which NR2B is overexpressed in the cortex and hippocampus and
      investigated the role of NR2B gene in NMDA receptor-mediated synaptic plasticity
      and memory functions by combining electrophysiological technique with behavioral
      measurements. We found that overexpression of the NR2B subunit had no effect on
      CA1-LTD, but rather resulted in enhanced CA1-LTP and improved memory performances
      in novel object recognition test, spatial water maze, and delayed-to-nonmatch
      working memory test. Our slices recordings using NR2A- and NR2B-selective
      antagonists further demonstrate that the larger LTP in transgenic hippocampal
      slices was due to contribution from the increased NR2B-containing NMDARs.
      Therefore, our genetic experiments suggest that NR2B at CA1 synapses is not
      designated as a rate-limiting factor for the induction of long-term synaptic
      depression, but rather plays a crucial role in initiating the synaptic
      potentiation. Moreover, our studies provide strong evidence that the NR2B subunit
      represents a universal rate-limiting molecule for gating NMDA receptor's optimal
      coincidence-detection property and for enhancing memory function in adulthood
      across multiple mammalian species.

PMID- 19838303
TI  - Glycerol monolaurate and dodecylglycerol effects on Staphylococcus aureus and
      toxic shock syndrome toxin-1 in vitro and in vivo.
AB  - BACKGROUND: Glycerol monolaurate (GML), a 12 carbon fatty acid monoester,
      inhibits Staphylococcus aureus growth and exotoxin production, but is degraded by
      S. aureus lipase. Therefore, dodecylglycerol (DDG), a 12 carbon fatty acid
      monoether, was compared in vitro and in vivo to GML for its effects on S. aureus
      growth, exotoxin production, and stability. METHODOLOGY/PRINCIPAL FINDINGS:
      Antimicrobial effects of GML and DDG (0 to 500 microg/ml) on 54 clinical isolates
      of S. aureus, including pulsed-field gel electrophoresis (PFGE) types USA200,
      USA300, and USA400, were determined in vitro. A rabbit Wiffle ball infection
      model assessed GML and DDG (1 mg/ml instilled into the Wiffle ball every other
      day) effects on S. aureus (MN8) growth (inoculum 3x10(8) CFU/ml), toxic shock
      syndrome toxin-1 (TSST-1) production, tumor necrosis factor-alpha (TNF-alpha)
      concentrations and mortality over 7 days. DDG (50 and 100 microg/ml) inhibited S.
      aureus growth in vitro more effectively than GML (p<0.01) and was stable to
      lipase degradation. Unlike GML, DDG inhibition of TSST-1 was dependent on S.
      aureus growth. GML-treated (4 of 5; 80%) and DDG-treated rabbits (2 of 5; 40%)
      survived after 7 days. Control rabbits (5 of 5; 100%) succumbed by day 4. GML
      suppressed TNF-alpha at the infection site on day 7; however, DDG did not (<10
      ng/ml versus 80 ng/ml, respectively). CONCLUSIONS/SIGNIFICANCE: These data
      suggest that DDG was stable to S. aureus lipase and inhibited S. aureus growth at
      lower concentrations than GML in vitro. However, in vivo GML was more effective
      than DDG by reducing mortality, and suppressing TNF-alpha, S. aureus growth and
      exotoxin production, which may reduce toxic shock syndrome. GML is proposed as a
      more effective anti-staphylococcal topical anti-infective candidate than DDG,
      despite its potential degradation by S. aureus lipase.

PMID- 19838304
TI  - Cyp26b1 expression in murine Sertoli cells is required to maintain male germ
      cells in an undifferentiated state during embryogenesis.
AB  - In mammals, germ cells within the developing gonad follow a sexually dimorphic
      pathway. Germ cells in the murine ovary enter meiotic prophase during
      embryogenesis, whereas germ cells in the embryonic testis arrest in G0 of mitotic
      cell cycle and do not enter meiosis until after birth. In mice, retinoic acid
      (RA) signaling has been implicated in controlling entry into meiosis in germ
      cells, as meiosis in male embryonic germ cells is blocked by the activity of a RA
      catabolizing enzyme, CYP26B1. However, the mechanisms regulating mitotic arrest
      in male germ cells are not well understood. Cyp26b1 expression in the testes
      begins in somatic cells at embryonic day (E) 11.5, prior to mitotic arrest, and
      persists throughout fetal development. Here, we show that Sertoli cell-specific
      loss of CYP26B1 activity between E15.5 and E16.5, several days after germ cell
      sex determination, causes male germ cells to exit from G0, re-enter the mitotic
      cell cycle and initiate meiotic prophase. These results suggest that male germ
      cells retain the developmental potential to differentiate in meiosis until at
      least at E15.5. CYP26B1 in Sertoli cells acts as a masculinizing factor to arrest
      male germ cells in the G0 phase of the cell cycle and prevents them from entering
      meiosis, and thus is essential for the maintenance of the undifferentiated state
      of male germ cells during embryonic development.

PMID- 19838305
TI  - Genome-wide identification of transcription start sites, promoters and
      transcription factor binding sites in E. coli.
AB  - Despite almost 40 years of molecular genetics research in Escherichia coli a
      major fraction of its Transcription Start Sites (TSSs) are still unknown,
      limiting therefore our understanding of the regulatory circuits that control gene
      expression in this model organism. RegulonDB (http://regulondb.ccg.unam.mx/) is
      aimed at integrating the genetic regulatory network of E. coli K12 as an entirely
      bioinformatic project up till now. In this work, we extended its aims by
      generating experimental data at a genome scale on TSSs, promoters and regulatory
      regions. We implemented a modified 5' RACE protocol and an unbiased High
      Throughput Pyrosequencing Strategy (HTPS) that allowed us to map more than 1700
      TSSs with high precision. From this collection, about 230 corresponded to
      previously reported TSSs, which helped us to benchmark both our methodologies and
      the accuracy of the previous mapping experiments. The other ca 1500 TSSs mapped
      belong to about 1000 different genes, many of them with no assigned function. We
      identified promoter sequences and type of sigma factors that control the
      expression of about 80% of these genes. As expected, the housekeeping sigma(70)
      was the most common type of promoter, followed by sigma(38). The majority of the
      putative TSSs were located between 20 to 40 nucleotides from the translational
      start site. Putative regulatory binding sites for transcription factors were
      detected upstream of many TSSs. For a few transcripts, riboswitches and small
      RNAs were found. Several genes also had additional TSSs within the coding region.
      Unexpectedly, the HTPS experiments revealed extensive antisense transcription,
      probably for regulatory functions. The new information in RegulonDB, now with
      more than 2400 experimentally determined TSSs, strengthens the accuracy of
      promoter prediction, operon structure, and regulatory networks and provides
      valuable new information that will facilitate the understanding from a global
      perspective the complex and intricate regulatory network that operates in E.
      coli.

PMID- 19838306
TI  - Unravelling the relationship between animal growth and immune response during
      micro-parasitic infections.
AB  - BACKGROUND: Both host genetic potentials for growth and disease resistance, as
      well as nutrition are known to affect responses of individuals challenged with
      micro-parasites, but their interactive effects are difficult to predict from
      experimental studies alone. METHODOLOGY/PRINCIPAL FINDINGS: Here, a mathematical
      model is proposed to explore the hypothesis that a host's response to pathogen
      challenge largely depends on the interaction between a host's genetic capacities
      for growth or disease resistance and the nutritional environment. As might be
      expected, the model predicts that if nutritional availability is high, hosts with
      higher growth capacities will also grow faster under micro-parasitic challenge,
      and more resistant animals will exhibit a more effective immune response. Growth
      capacity has little effect on immune response and resistance capacity has little
      effect on achieved growth. However, the influence of host genetics on phenotypic
      performance changes drastically if nutrient availability is scarce. In this case
      achieved growth and immune response depend simultaneously on both capacities for
      growth and disease resistance. A higher growth capacity (achieved e.g. through
      genetic selection) would be detrimental for the animal's ability to cope with
      pathogens and greater resistance may reduce growth in the short-term.
      SIGNIFICANCE: Our model can thus explain contradicting outcomes of genetic
      selection observed in experimental studies and provides the necessary biological
      background for understanding the influence of selection and/or changes in the
      nutritional environment on phenotypic growth and immune response.

PMID- 19838308
TI  - Molecular characterization of the symbionts associated with marine nematodes of
      the genus Robbea.
AB  - Marine nematodes that carry sulfur-oxidizing bacteria on their cuticle
      (Stilbonematinae, Desmodoridae) migrate between oxidized and reduced sand layers
      thereby supplying their symbionts with oxygen and sulfide. These symbionts, in
      turn, constitute the worms' major food source. Due to the accessibility,
      abundance and relative simplicity of this association, stilbonematids may be
      useful to understand symbiosis establishment. Nevertheless, only the symbiont of
      Laxus oneistus has been found to constitute one single phylotype within the
      Gammaproteobacteria. Here, we characterized the symbionts of three yet
      undescribed nematodes that were morphologically identified as members of the
      genus Robbea. They were collected at the island of Corsica, the Cayman Islands
      and the Belize Barrier Reef. The surface of these worms is covered by a single
      layer of morphologically undistinguishable bacteria. 18S rDNA-based phylogenetic
      analysis showed that all three species belong to the Stilbonematinae, although
      they do not form a distinct cluster within that subfamily. 16S rDNA-based
      analysis of the symbionts placed them interspersed in the cluster comprising the
      sulfur-oxidizing symbionts of L. oneistus and of marine gutless oligochaetes.
      Finally, the presence and phylogeny of the aprA gene indicated that the symbionts
      of all three nematodes can use reduced sulfur compounds as an energy source.

PMID- 19838309
TI  - Young's modulus and degree of conversion of different combination of light-cure
      dental resins.
AB  - OBJECTIVES: To evaluate Young's modulus and degree of conversion of several
      combinations of bisGMA, UEDMA, TEGDMA light-cure dental resin. METHODS: Young's
      modulus and DC% were studied for 21 different resin combinations of bisGMA,
      TEGDMA and UEDMA. Small universal testing machine and photo-calorimetry were used
      for the tests. The results were evaluated using ANOVA and Duncan's multiple range
      tests and regular t-test. RESULTS: Young's modulus varied between 2.37+/-0.2 GPa
      (100% TEGDMA) and 4.15+/-0.2 GPa (100% bisGMA). By adding TEGDMA to bisGMA or
      UEDMA, the Young's modulus decreased significantly (p<0.05). Degree of conversion
      was significantly (p<0.05) higher when the wt% of TEGDMA was high in the mixtures
      than for highly concentrated bis-GMA (resin mixtures with TEGDMA in comparison to
      mixture with bisGMA had higher degree of conversion). DC% was significantly
      higher (p<0.05) for binary mixtures of UEDMA and TEGDMA, and significantly lower
      for 100 wt% bis-GMA (p<0.05). The DC% values were between 53.1%+/-0.9% (100%
      bisGMA) and 85.6%+/-1% (80% UEDMA-20% TEGDMA). The concentration of bisGMA, in
      the monomer mixture, affected DC% and Young's modulus oppositely. CONCLUSIONS:
      The differences in the values for DC% were mostly justified by the differences in
      the molecular structures of the different monomers. It was also revealed that
      higher DC% does not always result in a higher Young's modulus, because molecular
      and network structural parameters play major roles in the final physical
      properties of the mixtures.

PMID- 19838307
TI  - Human placental-specific epipolymorphism and its association with adverse
      pregnancy outcomes.
AB  - Interindividual variation in DNA-methylation level is widespread in the human
      genome, despite its critical role in regulating gene expression. The nature of
      this variation, including its tissue-specific nature, and the role it may play in
      human phenotypic variation and disease is still poorly characterized. The
      placenta plays a critical role in regulating fetal growth and development in ways
      that have lifelong effects on health. To identify genes with a high degree of
      interindividual DNA methylation variation in the human placenta, we surveyed the
      human genome using the Illumina GoldenGate Methylation Cancer panel targeting
      1505 CpG sites of 807 genes. While many sites show a continuous pattern of
      methylation levels, WNT2, TUSC3 and EPHB4 were identified to have a polymorphic
      "on-or-off" pattern of DNA methylation variation at their promoter region which
      was confirmed by pyrosequencing. Methylation of these genes can be found in 7%
      25% of over 100 placentas tested. The methylation state at the promoter of these
      genes is concordant with mRNA allelic expression. In three informative cases
      TUSC3 was observed to be methylated on the maternal allele, and it is thus
      possible this represents a polymorphically imprinted gene. Furthermore, TUSC3
      promoter methylation showed evidence for association with preeclampsia. A
      biological significance of these methylation allelic polymorphisms (MAPs) to
      human placental diversity is further implied by their placental specificity and
      absence in mouse. An extended study of blood suggests that MAPs may also be found
      in other tissues, implicating their utility for tissue-specific association with
      complex disorders. The identification of such "epipolymorphism" in other tissues
      and their use in association studies, should improve our understanding of
      interindividual phenotypic variability and complex disease susceptibility.

PMID- 19838310
TI  - Maternal stress and perinatal programming in the expression of atopy.

PMID- 19838312
TI  - Estimating Load-Sharing Properties in a Dynamic Reliability System.
AB  - An estimator for the load share parameters in an equal load-share model is
      derived based on observing k-component parallel systems of identical components
      that have a continuous distribution function F (.) and failure rate r(.). In an
      equal load share model, after the first of k components fails, failure rates for
      the remaining components change from r(t) to gamma(1)r(t), then to gamma(2)r(t)
      after the next failure, and so on. On the basis of observations on n independent
      and identical systems, a semiparametric estimator of the component baseline
      cumulative hazard function R = - log(1 - F) is presented, and its asymptotic
      limit process is established to be a Gaussian process. The effect of estimation
      of the load-share parameters is considered in the derivation of the limiting
      process. Potential applications can be found in diverse areas, including
      materials testing, software reliability and power plant safety assessment.

PMID- 19838311
TI  - A Meta-Analysis of Ethics Instruction Effectiveness in the Sciences.
AB  - Scholars have proposed a number of courses and programs intended to improve the
      ethical behavior of scientists in an attempt to maintain the integrity of the
      scientific enterprise. In the present study, we conducted a quantitative meta
      analysis based on 26 previous ethics program evaluation efforts, and the results
      showed that the overall effectiveness of ethics instruction was modest. The
      effects of ethics instruction, however, were related to a number of instructional
      program factors, such as course content and delivery methods, in addition to
      factors of the evaluation study itself, such as the field of investigator and
      criterion measure utilized. An examination of the characteristics contributing to
      the relative effectiveness of instructional programs revealed that more
      successful programs were conducted as seminars separate from the standard
      curricula rather than being embedded in existing courses. Furthermore, more
      successful programs were case-based, interactive and allowed participants to
      learn and practice the application of real-world ethical decision-making skills.
      The implications of these findings for future course development and evaluation
      are discussed.

PMID- 19838313
TI  - PROPORTIONAL HAZARDS MODELS WITH CONTINUOUS MARKS.
AB  - For time-to-event data with finitely many competing risks, the proportional
      hazards model has been a popular tool for relating the cause-specific outcomes to
      covariates [Prentice et al. Biometrics34 (1978) 541-554]. This article studies an
      extension of this approach to allow a continuum of competing risks, in which the
      cause of failure is replaced by a continuous mark only observed at the failure
      time. We develop inference for the proportional hazards model in which the
      regression parameters depend nonparametrically on the mark and the baseline
      hazard depends nonparametrically on both time and mark. This work is motivated by
      the need to assess HIV vaccine efficacy, while taking into account the genetic
      divergence of infecting HIV viruses in trial participants from the HIV strain
      that is contained in the vaccine, and adjusting for covariate effects. Mark
      specific vaccine efficacy is expressed in terms of one of the regression
      functions in the mark-specific proportional hazards model. The new approach is
      evaluated in simulations and applied to the first HIV vaccine efficacy trial.

PMID- 19838314
TI  - Hydrodynamics and sediment transport in a southeast Florida tidal inlet.
AB  - A three-dimensional ocean circulation model is used to investigate the
      hydrodynamics of a tidal inlet and deltas system in Southeast Florida, and to
      understand the consequences for suspended and bedload sediment transport
      patterns. The model reproduces observed tidal currents and provides insight about
      residual currents caused by spatial asymmetries in the inlet throat and tidal
      deltas during ebb and flood flows. A particle-tracking approach for suspended and
      bedload sediment transport is used to simulate deposition patterns for different
      particle sizes. The simulation results qualitatively correlate with the
      distribution of sediment characteristics within the tidal inlet and deltas system
      and demonstrate sensitivity to the choice of advection velocities (e.g., near
      bottom versus depth-averaged) and regions of sediment origin. Furthermore, the
      distinction between suspended and bedload transport as a function of particle
      size indicates significant differences in deposition patterns and their potential
      connection to geomorphologic features of the tidal inlet and deltas system.

PMID- 19838315
TI  - A Linear Magnetic Field Scan Driver.
AB  - A linear magnetic field scan driver was developed to provide a rapidly scanning
      magnetic field for use in electron paramagnetic resonance (EPR) spectroscopy. The
      driver consists of two parts: a digitally synthesized ramp waveform generator and
      a power amplifier to drive the magnetic field coils. Additionally, the driver
      provides a trigger signal to a data collection digitizer that is synchronized to
      the ramp waveform. The driver can also drive an arbitrary current waveform
      supplied from an external source. The waveform generator is computer controlled
      through a serial data interface. Additional functions are controlled by the user
      from the driver front panel. The frequency and amplitude of the waveform are each
      separately controlled with 12-bit resolution (one part in 4,096). Several
      versions of the driver have been built with different frequency and amplitude
      ranges. Frequencies range from 500 to 20,000 Hz. Field sweep amplitudes range up
      to 80 G(pp). This article also gives a brief description of the field coils that
      are driven by the driver.

PMID- 19838316
TI  - Multi-View AAM Fitting and Construction.
AB  - Active Appearance Models (AAMs) are generative, parametric models that have been
      successfully used in the past to model deformable objects such as human faces.
      The original AAMs formulation was 2D, but they have recently been extended to
      include a 3D shape model. A variety of single-view algorithms exist for fitting
      and constructing 3D AAMs but one area that has not been studied is multi-view
      algorithms. In this paper we present multi-view algorithms for both fitting and
      constructing 3D AAMs.Fitting an AAM to an image consists of minimizing the error
      between the input image and the closest model instance; i.e. solving a nonlinear
      optimization problem. In the first part of the paper we describe an algorithm for
      fitting a single AAM to multiple images, captured simultaneously by cameras with
      arbitrary locations, rotations, and response functions. This algorithm uses the
      scaled orthographic imaging model used by previous authors, and in the process of
      fitting computes, or calibrates, the scaled orthographic camera matrices. In the
      second part of the paper we describe an extension of this algorithm to calibrate
      weak perspective (or full perspective) camera models for each of the cameras. In
      essence, we use the human face as a (non-rigid) calibration grid. We demonstrate
      that the performance of this algorithm is roughly comparable to a standard
      algorithm using a calibration grid. In the third part of the paper, we show how
      camera calibration improves the performance of AAM fitting.A variety of non-rigid
      structure-from-motion algorithms, both single-view and multi-view, have been
      proposed that can be used to construct the corresponding 3D non-rigid shape
      models of a 2D AAM. In the final part of the paper, we show that constructing a
      3D face model using non-rigid structure-from-motion suffers from the Bas-Relief
      ambiguity and may result in a "scaled" (stretched/compressed) model. We outline a
      robust non-rigid motion-stereo algorithm for calibrated multi-view 3D AAM
      construction and show how using calibrated multi-view motion-stereo can eliminate
      the Bas-Relief ambiguity and yield face models with higher 3D fidelity.

PMID- 19838317
TI  - Testing in semiparametric models with interaction, with applications to gene
      environment interactions.
AB  - Motivated from the problem of testing for genetic effects on complex traits in
      the presence of gene-environment interaction, we develop score tests in general
      semiparametric regression problems that involves Tukey style 1 degree-of-freedom
      form of interaction between parametrically and non-parametrically modelled
      covariates. We find that the score test in this type of model, as recently
      developed by Chatterjee and co-workers in the fully parametric setting, is biased
      and requires undersmoothing to be valid in the presence of non-parametric
      components. Moreover, in the presence of repeated outcomes, the asymptotic
      distribution of the score test depends on the estimation of functions which are
      defined as solutions of integral equations, making implementation difficult and
      computationally taxing. We develop profiled score statistics which are unbiased
      and asymptotically efficient and can be performed by using standard bandwidth
      selection methods. In addition, to overcome the difficulty of solving functional
      equations, we give easy interpretations of the target functions, which in turn
      allow us to develop estimation procedures that can be easily implemented by using
      standard computational methods. We present simulation studies to evaluate type I
      error and power of the method proposed compared with a naive test that does not
      consider interaction. Finally, we illustrate our methodology by analysing data
      from a case-control study of colorectal adenoma that was designed to investigate
      the association between colorectal adenoma and the candidate gene NAT2 in
      relation to smoking history.

PMID- 19838318
TI  - EARLY WITHDRAWAL FROM MENTAL HEALTH TREATMENT: IMPLICATIONS FOR PSYCHOTHERAPY
      PRACTICE.
AB  - Despite more than 50 years of research on client attrition from therapy,
      obstacles to the delivery and success of treatments remain poorly understood, and
      effective methods to engage and retain clients in therapy are lacking. This
      article offers a review of the literature on attrition, highlighting the
      methodological challenges in effectively addressing the complex nature of this
      problem. Current interventions for reducing attrition are reviewed, and
      recommendations for implementing these interventions into psychotherapy practice
      are discussed.

PMID- 19838319
TI  - Ecological theory to enhance infectious disease control and public health policy.
AB  - Through the work of international public health organizations and advancements in
      the biological and technological sciences, substantial progress has been made in
      our ability to prevent, control, locally eliminate, and in one case eradicate
      infectious diseases. Yet each successful control or local elimination has been
      met with the emergence of new pathogens, the evolution of novel strains, or
      different epidemiological circumstances that have limited or reversed control
      methods. To respond to the increasing threat of emerging infectious diseases and
      bioterrorism it is vital that we design and implement efficient programs that
      prevent and control infectious pathogen transmission. The theoretical tools of
      ecology and epidemiology may be the cornerstone in constructing future programs
      aimed at preventing and controlling infectious diseases throughout the world.

PMID- 19838320
TI  - Successful Aging with Sickle Cell Disease: Using Qualitative Methods to Inform
      Theory.
AB  - Little is known about the lives of adults with sickle cell disease (SCD). This
      article reports findings from a qualitative pilot study, which used life review
      as a method to explore influences on health outcomes among middle-aged and older
      adults with SCD, Six females with SCD, recruited from two urban sickle cell
      clinics in the U.S., engaged in semi-structured, in-depth life review interviews.
      MaxQDA2 software was used for qualitative data coding and analysis. Three major
      themes were identified: vulnerability factors, self-care management resources,
      and health outcomes. These themes are consistent with the Theory of Self-Care
      Management for Sickle Cell Disease. Identifying vulnerability factors, self-care
      management resources, and health outcomes in adults with SCD may aid in
      developing theory-based interventions to meet health care needs of younger
      individuals with SCD. The life review process is a useful means to gain insight
      into successful aging with SCD and other chronic illnesses.

PMID- 19838321
TI  - ?
AB  - INTRODUCTION: Impulsivity is a complex personality trait related to the control
      of behavior and emotions and it is present in a wide variety of psychiatric
      diseases, including eating disorders and particularly in bulimia nervosa (BN).
      Yet, the relationship between impulsivity and bulimia nervosa, as well as the
      neurobiological substrates of these disorders, are difficult to discern.
      OBJECTIVES: The present manuscript reviews the neural substrates for impulsivity,
      including executive function, preference formation and emotional regulation, and
      the function of these circuits in individuals with BN. METHODS: A selective
      review of the literature related to the subject was performed. RESULTS AND
      CONCLUSIONS: The discussion illustrates the complex relationship between
      impulsivity and BN, where impulsivity may serve as a vulnerability factor that
      sensitizes the subjects with BN to negative emotional states that bias the impact
      of environmental and internal stimuli over behavioral regulation processes,
      favoring maladaptive and inflexible behavioral patterns.

PMID- 19838322
TI  - EMPIRICAL LIKELIHOOD INFERENCE FOR THE COX MODEL WITH TIME-DEPENDENT COEFFICIENTS
      VIA LOCAL PARTIAL LIKELIHOOD.
AB  - The Cox model with time-dependent coefficients has been studied by a number of
      authors recently. In this paper, we develop empirical likelihood (EL) pointwise
      confidence regions for the time-dependent regression coefficients via local
      partial likelihood smoothing. The EL simultaneous confidence bands for a linear
      combination of the coefficients are also derived based on the strong
      approximation methods. The empirical likelihood ratio is formulated through the
      local partial log-likelihood for the regression coefficient functions. Our
      numerical studies indicate that the EL pointwise/simultaneous confidence
      regions/bands have satisfactory finite sample performances. Compared with the
      confidence regions derived directly based on the asymptotic normal distribution
      of the local constant estimator, the EL confidence regions are overall tighter
      and can better capture the curvature of the underlying regression coefficient
      functions. Two data sets, the gastric cancer data and the Mayo Clinic primary
      biliary cirrhosis data, are analyzed using the proposed method.

PMID- 19838323
TI  - Postnatal experiences influence how the brain integrates information from
      different senses.
AB  - Sensory processing disorder (SPD) is characterized by anomalous reactions to, and
      integration of, sensory cues. Although the underlying etiology of SPD is unknown,
      one brain region likely to reflect these sensory and behavioral anomalies is the
      superior colliculus (SC), a structure involved in the synthesis of information
      from multiple sensory modalities and the control of overt orientation responses.
      In the present review we describe normal functional properties of this structure,
      the manner in which its individual neurons integrate cues from different senses,
      and the overt SC-mediated behaviors that are believed to manifest this
      "multisensory integration." Of particular interest here is how SC neurons develop
      their capacity to engage in multisensory integration during early postnatal life
      as a consequence of early sensory experience, and the intimate communication
      between cortex and the midbrain that makes this developmental process possible.

PMID- 19838324
TI  - Signals, synapses, and synthesis: how new proteins control plasticity.
AB  - Localization of mRNAs to dendrites and local protein synthesis afford spatial and
      temporal regulation of gene expression and endow synapses with the capacity to
      autonomously alter their structure and function. Emerging evidence indicates that
      RNA binding proteins, ribosomes, translation factors and mRNAs encoding proteins
      critical to synaptic structure and function localize to neuronal processes. RNAs
      are transported into dendrites in a translationally quiescent state where they
      are activated by synaptic stimuli. Two RNA binding proteins that regulate
      dendritic RNA delivery and translational repression are cytoplasmic
      polyadenylation element binding protein and fragile X mental retardation protein
      (FMRP). The fragile X syndrome (FXS) is the most common known genetic cause of
      autism and is characterized by the loss of FMRP. Hallmark features of the FXS
      include dysregulation of spine morphogenesis and exaggerated metabotropic
      glutamate receptor-dependent long term depression, a cellular substrate of
      learning and memory. Current research focuses on mechanisms whereby mRNAs are
      transported in a translationally repressed state from soma to distal process and
      are activated at synaptic sites in response to synaptic signals.

PMID- 19838326
TI  - Stimulus size dependence of information transfer from retina to thalamus.
AB  - Relay cells in the mammalian lateral geniculate nucleus (LGN) are driven
      primarily by single retinal ganglion cells (RGCs). However, an LGN cell responds
      typically to less than half of the spikes it receives from the RGC that drives
      it, and without retinal drive the LGN is silent (Kaplan and Shapley, 1984).
      Recent studies, which used stimuli restricted to the receptive field (RF) center,
      show that despite the great loss of spikes, more than half of the information
      carried by the RGC discharge is typically preserved in the LGN discharge (Sincich
      et al., 2009), suggesting that the retinal spikes that are deleted by the LGN
      carry less information than those that are transmitted to the cortex. To
      determine how LGN relay neurons decide which retinal spikes to respond to, we
      recorded extracellularly from the cat LGN relay cell spikes together with the
      slow synaptic ('S') potentials that signal the firing of retinal spikes. We
      investigated the influence of the inhibitory surround of the LGN RF by
      stimulating the eyes with spots of various sizes, the largest of which covered
      the center and surround of the LGN relay cell's RF. We found that for stimuli
      that activated mostly the RF center, each LGN spike delivered more information
      than the retinal spike, but this difference was reduced as stimulus size
      increased to cover the RF surround. To evaluate the optimality of the LGN editing
      of retinal spikes, we created artificial spike trains from the retinal ones by
      various deletion schemes. We found that single LGN cells transmitted less
      information than an optimal detector could.

PMID- 19838327
TI  - Taguchi loss function for varus/valgus alignment in total knee arthroplasty.
AB  - Methods of designing equipment to improve quality have been developed by Taguchi.
      A key feature of these methods is the development of loss function, which
      quantifies the financial cost (loss) resulting from deviations from target
      dimensions. Total knee arthroplasties can fail due to prosthetic component
      malalignment. A Taguchi loss function for varus/valgus alignment of the
      prosthesis and revision rates was developed. Six studies were identified from a
      comprehensive literature search. Varus and extreme valgus alignments correlated
      with an increased percentage of prosthetic failure. A loss function of L( y) =
      $326.80y(2) , where y was deviation from ideal varus/valgus angle, was
      determined. The expected loss function was EL=$326.80y 2+s2 , where y was the
      mean deviance from the ideal varus/valgus angle and s(2) was the variance in
      varus/valgus angle. This loss function was used to estimate the cost savings of
      using computer-assisted surgical navigation in total knee arthroplasty (TKA). The
      average savings of a navigated TKA versus a conventional TKA, based on the
      expected loss equation derived from the Taguchi loss function, was $2,304 per
      knee. The expected loss function derived here can serve as a tool for biomedical
      engineers seeking to use Taguchi quality engineering methods in designing
      orthopaedic devices.

PMID- 19838328
TI  - Resonant electron capture by some amino acids esters.
AB  - Resonant electron capture by Gly, Ala and Phe esters have shown that the most
      efficient negative ion (NI) fragmentations are associated with the C-termini. A
      new mechanism for the negative ion-forming processes at energies lower than those
      associated with the pi*(OO) shape resonance involves coupling between dipole
      bound and valence negative ion states of the same symmetry for amino acid
      conformers with high permanent dipoles. The interaction avoids crossing of the NI
      states and instead leads to formation of two adiabatic potential energy surfaces.
      Underivatized amino acids most effectively fragment from the bottom adiabatic
      surface via generation of [M-H](-) carboxylate anions by hydrogen-atom tunneling
      through the barrier; fragmentation of the their esters with formation of
      analogues [M-X](-) NIs occurs through the upper adiabatic state without
      penetration of the barrier in which the energy of the valence sigma*OX resonance
      exceeds the bond dissociation energy of the neutral molecule. Low and high
      temperature resonant electron capture experiments point to the importance of
      conformational preferences of the amino acids for optimum dissociation of the
      parent NIs in the gas phase.

PMID- 19838325
TI  - Early life stress as an influence on limbic epilepsy: an hypothesis whose time
      has come?
AB  - The pathogenesis of mesial temporal lobe epilepsy (MTLE), the most prevalent form
      of refractory focal epilepsy in adults, is thought to begin in early life, even
      though seizures may not commence until adolescence or adulthood. Amongst the
      range of early life factors implicated in MTLE causation (febrile seizures,
      traumatic brain injury, etc.), stress may be one important contributor. Early
      life stress is an a priori agent deserving study because of the large amount of
      neuroscientific data showing enduring effects on structure and function in
      hippocampus and amygdala, the key structures involved in MTLE. An emerging body
      of evidence directly tests hypotheses concerning early life stress and limbic
      epilepsy: early life stressors, such as maternal separation, have been shown to
      aggravate epileptogenesis in both status epilepticus and kindling models of
      limbic epilepsy. In addition to elucidating its influence on limbic
      epileptogenesis itself, the study of early life stress has the potential to shed
      light on the psychiatric disorder that accompanies MTLE. For many years,
      psychiatric comorbidity was viewed as an effect of epilepsy, mediated
      psychologically and/or neurobiologically. An alternative - or complementary -
      perspective is that of shared causation. Early life stress, implicated in the
      pathogenesis of several psychiatric disorders, may be one such causal factor.
      This paper aims to critically review the body of experimental evidence linking
      early life stress and epilepsy; to discuss the direct studies examining early
      life stress effects in current models of limbic seizures/epilepsy; and to suggest
      priorities for future research.

PMID- 19838329
TI  - RNA recognition motif (RRM) of La/SSB: the bridge for interparticle spreading of
      autoimmune response to U1-RNP.
AB  - Systemic lupus erythematosus (SLE) is characterized by the production of grouped
      sets of autoantibodies targeting mainly the U1 ribonucleoprotein (RNP) and/or
      Ro/La RNP particles. Intraparticle diversification of the autoimmune response is
      believed to occur via epitope spreading. So far, it is not known how the
      autoimmune response "jumps" from one particle to another. To the extent that the
      majority of nuclear autoantigens in SLE are RNA binding proteins and major
      epitopes were previously mapped within their RRM (RNA recognition motifs),
      conserved sequences within RRM could be involved in the intermolecular and inter
      particle diversification process of the autoimmune response. We investigated the
      potential of RRM of the La/SSB autoantigen to induce antibodies that cross
      recognize components of the U1-RNP particle and therefore its capacity to produce
      interparticle epitope spreading. We immunized New Zealand white rabbits with a
      peptide corresponding to the epitope 145-164 of La/SSB (belonging to the RRM of
      La/SSB), attached in four copies on a scaffold carrier. Sera were drawn from 20
      sera of patients with SLE and anti-U1-RNP antibodies and 26 sera of primary
      Sjogren syndrome patients with anti-La/SSB antibodies. All sera were evaluated
      for reactivity against the major epitope of La/SSB (pep349-364), the RNP antigen
      and the RRM-related epitope of La/SSB (pep145-164). Specific antibodies against
      pep145-164 were purified with immunoaffinity columns from selected sera. After
      the immunization of the animals with pep145-164, a specific IgG antibody response
      was detected, directed against the La/SSB autoantigen (wks 3-7), the immunizing
      peptide (wks 3-27), and the RNP autoantigen (wks 7-20). This response gradually
      decreased to low levels between postimmunization wks 27-42. Purified antibodies
      against pep145-164 recognized La/SSB and a 70-kD autoantigen in Western blot and
      exhibited significant reactivity in anti-U1-RNP ELISA. Depletion of anti-pep145
      164 antibodies eliminated anti-U1-RNP reactivity from immunized rabbit sera but
      not from human sera. In addition, pep145-164 was recognized to a greater extent
      by autoimmune sera with anti-RNP reactivity compared with anti-La/SSB-positive
      sera, in contrast to pep349-364 of La/SSB, which was recognized almost
      exclusively by sera with anti-La/SSB reactivity. These data suggest that the RRM
      region of La/SSB can trigger interparticle B-cell diversification to U1-RNP-70
      autoantigen via molecular mimicry. Identification of key sequences that trigger
      and perpetuate the autoimmune process is particularly important for understanding
      pathogenetic mechanisms in autoimmunity.

PMID- 19838330
TI  - Patterns of stochastic behavior in dynamically unstable high-dimensional
      biochemical networks.
AB  - The question of dynamical stability and stochastic behavior of large biochemical
      networks is discussed. It is argued that stringent conditions of asymptotic
      stability have very little chance to materialize in a multidimensional system
      described by the differential equations of chemical kinetics. The reason is that
      the criteria of asymptotic stability (Routh-Hurwitz, Lyapunov criteria,
      Feinberg's Deficiency Zero theorem) would impose the limitations of very high
      algebraic order on the kinetic rates and stoichiometric coefficients, and there
      are no natural laws that would guarantee their unconditional validity. Highly
      nonlinear, dynamically unstable systems, however, are not necessarily doomed to
      collapse, as a simple Jacobian analysis would suggest. It is possible that their
      dynamics may assume the form of pseudo-random fluctuations quite similar to a
      shot noise, and, therefore, their behavior may be described in terms of Langevin
      and Fokker-Plank equations. We have shown by simulation that the resulting pseudo
      stochastic processes obey the heavy-tailed Generalized Pareto Distribution with
      temporal sequence of pulses forming the set of constituent-specific Poisson
      processes. Being applied to intracellular dynamics, these properties are
      naturally associated with burstiness, a well documented phenomenon in the biology
      of gene expression.

PMID- 19838331
TI  - RNAi-mediated knockdown showing impaired cell survival in Drosophila wing
      imaginal disc.
AB  - The genetically amenable organism Drosophila melanogaster has been estimated to
      have 14,076 protein coding genes in the genome, according to the flybase release
      note R5.13 (http://flybase.bio.indiana.edu/static_pages/docs/release_notes.html).
      Recent application of RNA interference (RNAi) to the study of developmental
      biology in Drosophila has enabled us to carry out a systematic investigation of
      genes affecting various specific phenotypes. In order to search for genes
      supporting cell survival, we conducted an immunohistochemical examination in
      which the RNAi of 2,497 genes was independently induced within the dorsal
      compartment of the wing imaginal disc. Under these conditions, the activities of
      a stress-activated protein kinase JNK (c-Jun N-terminal kinase) and apoptosis
      executing factor Caspase-3 were monitored. Approximately half of the genes
      displayed a strong JNK or Caspase-3 activation when their RNAi was induced. Most
      of the JNK activation accompanied Caspase-3 activation, while the opposite did
      not hold true. Interestingly, the area activating Caspase-3 was more broadly seen
      than that activating JNK, suggesting that JNK is crucial for induction of non
      autonomous apoptosis in many cases. Furthermore, the RNAi of essential factors
      commonly regulating transcription and translation showed a severe and cell
      autonomous apoptosis but also elicited another apoptosis at an adjacent area in a
      non-autonomous way. We also found that the frequency of apoptosis varies
      depending on the tissues.

PMID- 19838332
TI  - A novel function of ethylene.
AB  - The cellular slime mold, Dictyostelium mucoroides-7 (Dm7) exhibits clear
      dimorphism; macrocyst formation as a sexual process and sorocap formation as an
      asexual process. These two life cycles are regulated by two regulators, ethylene
      and cyclic AMP (cAMP). This is the first report demonstrating a novel function of
      ethylene at the cellular level. That is, ethylene induces a zygote formed by cell
      fusion and subsequent nuclear fusion. Recently, the function of ethylene at the
      molecular level has been clarified as it induces zygote formation through an
      enhanced expression of a novel gene, zyg1. The signaling pathway for induction or
      inhibition of zygote formation is now trying to be clarified focusing on the ZYG1
      protein.

PMID- 19838334
TI  - An effective tri-clustering algorithm combining expression data with gene
      regulation information.
AB  - MOTIVATION: Bi-clustering algorithms aim to identify sets of genes sharing
      similar expression patterns across a subset of conditions. However direct
      interpretation or prediction of gene regulatory mechanisms may be difficult as
      only gene expression data is used. Information about gene regulators may also be
      available, most commonly about which transcription factors may bind to the
      promoter region and thus control the expression level of a gene. Thus a method to
      integrate gene expression and gene regulation information is desirable for
      clustering and analyzing. METHODS: By incorporating gene regulatory information
      with gene expression data, we define regulated expression values (REV) as
      indicators of how a gene is regulated by a specific factor. Existing bi
      clustering methods are extended to a three dimensional data space by developing a
      heuristic TRI-Clustering algorithm. An additional approach named Automatic
      Boundary Searching algorithm (ABS) is introduced to automatically determine the
      boundary threshold. RESULTS: Results based on incorporating ChIP-chip data
      representing transcription factor-gene interactions show that the algorithms are
      efficient and robust for detecting tri-clusters. Detailed analysis of the tri
      cluster extracted from yeast sporulation REV data shows genes in this cluster
      exhibited significant differences during the middle and late stages. The
      implicated regulatory network was then reconstructed for further study of defined
      regulatory mechanisms. Topological and statistical analysis of this network
      demonstrated evidence of significant changes of TF activities during the
      different stages of yeast sporulation, and suggests this approach might be a
      general way to study regulatory networks undergoing transformations.

PMID- 19838333
TI  - Post-transcriptional control of chloroplast gene expression.
AB  - Chloroplasts contain their own genome, organized as operons, which are generally
      transcribed as polycistronic transcriptional units. These primary transcripts are
      processed into smaller RNAs, which are further modified to produce functional
      RNAs. The RNA processing mechanisms remain largely unknown and represent an
      important step in the control of chloroplast gene expression. Such mechanisms
      include RNA cleavage of pre-existing RNAs, RNA stabilization, intron splicing,
      and RNA editing. Recently, several nuclear-encoded proteins that participate in
      diverse plastid RNA processing events have been characterised. Many of them seem
      to belong to the pentatricopeptide repeat (PPR) protein family that is implicated
      in many crucial functions including organelle biogenesis and plant development.
      This review will provide an overview of current knowledge of the post
      transcriptional processing in chloroplasts.

PMID- 19838337
TI  - Letter to the editor: Does dicer expression affect shRNA processing?
AB  - Elevated Dicer and Drosha mRNA levels have been documented across a range of
      tumor types (including ovarian carcinoma) by a number of investigators without
      any demonstrable correlation with patient survival nor evidence of interference
      with shRNA processing. A recent publication by Merritt et al. (NEJM 359(25):2641
      50, 2008) reporting their findings in patients with ovarian carcinoma reach
      opposite conclusions. Further study will be needed to resolve this issue.

PMID- 19838336
TI  - Safety and in vivo expression of a GNE-transgene: a novel treatment approach for
      hereditary inclusion body myopathy-2.
AB  - Hereditary inclusion body myopathy-2 (HIBM2) is an adult-onset, muscular disease
      caused by mutations in the GNE gene. HIBM2-associated GNE mutations causing
      hyposialyation have been proposed to contribute to reduced muscle function in
      patients with HIBM2, though the exact cause of this disease is unknown. In the
      current studies we examined pre-clinical in vivo toxicity, and expression of the
      plasmid-based, CMV driven wild-type GNE plasmid vector. The plasmid vector was
      injected intramuscularly (IM) or systemically (IV) into BALB/c mice, following
      encapsulation in a cationic liposome (DOTAP:Cholesterol). Single IM injections of
      the GNE-lipoplex at 40 microg did not produce overt toxicity or deaths,
      indicating that the no observable adverse effect level (NOAEL) dose for IM
      injection was >or=40 microg. Single intravenous (IV) infusion of GNE-lipoplex was
      lethal in 33% of animals at 100 microg dose, with a small proportion of animals
      in the 40 microg cohort demonstrating transient toxicity. Thus the NOAEL dose by
      the IV route was greater than 10 microg and less than or equal to 40 microg. Real
      time RT-qPCR analysis demonstrated recombinant human GNE mRNA expression in 100%
      of muscle tissues that received IM injection of 40 microg GNE-lipoplex, at 2
      weeks. These results indicate that GNE-lipoplex gene transfer is safe and can
      produce durable transgene expression in treated muscles. Our findings support
      future exploration of the clinical efficacy of GNE-lipoplex for experimental gene
      therapy of HIBM2.

PMID- 19838335
TI  - Sigma factors for cyanobacterial transcription.
AB  - Cyanobacteria are photosynthesizing microorganisms that can be used as a model
      for analyzing gene expression. The expression of genes involves transcription and
      translation. Transcription is performed by the RNA polymerase (RNAP) holoenzyme,
      comprising a core enzyme and a sigma (sigma) factor which confers promoter
      selectivity. The unique structure, expression, and function of cyanobacterial
      sigma factors (and RNAP core subunits) are summarized here based on studies,
      reported previously. The types of promoter recognized by the sigma factors are
      also discussed with regard to transcriptional regulation.

PMID- 19838338
TI  - Application of Petri nets in bone remodeling.
AB  - Understanding a mechanism of bone remodeling is a challenging task for both life
      scientists and model builders, since this highly interactive and nonlinear
      process can seldom be grasped by simple intuition. A set of ordinary differential
      equations (ODEs) have been built for simulating bone formation as well as bone
      resorption. Although solving ODEs numerically can provide useful predictions for
      dynamical behaviors in a continuous time frame, an actual bone remodeling process
      in living tissues is driven by discrete events of molecular and cellular
      interactions. Thus, an event-driven tool such as Petri nets (PNs), which may
      dynamically and graphically mimic individual molecular collisions or cellular
      interactions, seems to augment the existing ODE-based systems analysis. Here, we
      applied PNs to expand the ODE-based approach and examined discrete, dynamical
      behaviors of key regulatory molecules and bone cells. PNs have been used in many
      engineering areas, but their application to biological systems needs to be
      explored. Our PN model was based on 8 ODEs that described an osteoprotegerin
      linked molecular pathway consisting of 4 types of bone cells. The models allowed
      us to conduct both qualitative and quantitative evaluations and evaluate
      homeostatic equilibrium states. The results support that application of PN models
      assists understanding of an event-driven bone remodeling mechanism using PN
      specific procedures such as places, transitions, and firings.

PMID- 19838339
TI  - The goldfish SG2NA gene encodes two alpha-type regulatory subunits for PP-2A and
      displays distinct developmental expression pattern.
AB  - SG2NA is a member of the striatin protein family. In human and mouse, the SG2NA
      gene encodes two major protein isoforms: SG2NA alpha and SG2NA beta. The
      functions of these proteins, except for acting as the regulatory subunits for PP
      2A, remain largely unknown. To explore the possible functions of SG2NA in lower
      vertebrates, we have isolated two SG2NA cDNAs from goldfish, Carassius auratus.
      Our results reveal that the first cDNA contains an ORF of 2118 bp encoding a
      deduced protein with 705 amino acids, and the second one 2148 bp coding for a
      deduced protein of 715 amino acids. Comparative analysis reveals that both
      isoforms belong to the alpha-type, and are named SG2NA alpha and SG2NA alpha(+).
      RT-PCR and western blot analysis reveal that the SG2NA gene is differentially
      expressed in 9 tissues examined. During goldfish development, while the SG2NA
      mRNAs remain relatively constant in the first 3 stages and then become decreased
      and fluctuated from gastrula to larval hatching, the SG2NA proteins are
      fluctuated, displaying a peak every 3 to 4 stages. Each later peak is higher than
      the earlier one and the protein expression level becomes maximal at hatching
      stage. Together, our results reveal that SG2NA may play an important role during
      goldfish development and also in homeostasis of most adult tissues.

PMID- 19838340
TI  - Evaluation of the role of FGF23 in mineral metabolism.
AB  - Fibroblast growth factor 23 (FGF23) has recently been identified as a critical
      regulatory factor in phosphate (P) metabolism. Although the exact molecular
      mechanism of FGF23 synthesis through sensing the concentration of P is yet to be
      determined, experimental and clinical data indicate the influential role of FGF23
      in P and calcium (Ca) homeostasis. Here, we extended our previous mathematical
      model in calcium regulation and examined the conceivable roles of FGF23 in
      mineral metabolism. We assumed that the level of FGF23 was controlled through the
      concentrations of P and calcitriol in serum, and its actions such as lowering of
      the renal threshold for P, inhibition of the production of calcitriol in the
      kidney tubule, and inhibition of the production of parathyroid hormone (PTH) were
      included. Comparisons between the models with and without FGF23 demonstrate a
      complex interplay of FGF23 with calcitriol and PTH. In consistent with the model,
      our in vitro experimentation indicates that expression of FGF23 is activated in
      the presence of P though a G-protein linked receptor. We expect that further
      efforts on modeling and experimental evaluation would contribute to diagnosing
      patients with metabolic diseases such as osteoporosis and chronic kidney
      diseases, and developing FGF23-linked treatment strategies.

PMID- 19838341
TI  - Bone health - An investment.

PMID- 19838342
TI  - The art of retirement for orthopedic surgeons.

PMID- 19838343
TI  - Safety and efficacy of vertebroplasty: Early results of a prospective one-year
      case series of osteoporosis patients in an academic high-volume center.
AB  - BACKGROUND: Vertebroplasty (VP) is a cost-efficient alternative to kyphoplasty.
      However, it is considered inferior when it comes to maintaining safety and in
      vertebral body (VB) height restoration. We assess the safety and efficacy of VP
      in alleviating pain, improving quality of life (QoL), and restoring alignment.
      MATERIALS AND METHODS: In a prospective monocenter case series, from April 2007
      until July 2008, 1,422 vertebroplasties were performed, during 307 interventions,
      in 279 patients with traumatic, lytic, and osteoporotic fractures with 28 repeat
      interventions, for new fractures after the primary surgery, in 28 patients. The
      226 interventions (n=203 patients) done for osteoporotic fractures were analyzed
      for demographics, treatment and radiographic details, pain alleviation, QoL
      improvement [NASS and Euroqol (EQ-5D)] and complications. RESULTS: Osteoporotic
      patient sample consisted of 77.8% (n=158) females with a median age of 78 years
      and 45 males who had the same median age. Around 69% of these patients were ASA
      (American Society of Anesthesiologists) grade 3 and above. On an average there
      were 1.8 VBs fractured and five VBs treated,whereas the most frequently performed
      cementations were in six (35.6%, n=80) or five (19.6%, n=44) levels. About 36.5%,
      (n=414) of the interventions were localized at the thoraco-lumbar junction (Th12
      L2). On applying the Genant classification, there was a slight height reduction
      in 13.1% (n=29), a medium loss in 34.3% (n=78), and a severe loss of height in
      52.6% (n=119). The pre-operative pain was assessed by the visual analog scale
      (VAS) and decreased from 56.7 to 41.4 pts after two months. Accordingly, the QoL
      on the EQ-5D measure (0.6 to 1) improved from 0.32 pts before surgery to 0.58 pts
      after two months. The pre-operative Beck index (anterior height/posterior height)
      improved from a mean of 0.66 preoperative to 0.80 post-operative and remained
      stable at two months post-operatively. There were cement leakages in 33% of the
      fractured VBs and in 0.8% of the prophylactically cemented VBs; there were
      symptoms in 7.1%, and most of them were temporary hypotension and one pulmonary
      cement embolism that remained asymptomatic. CONCLUSION: If routinely used, VP is
      a safe and efficient treatment option for osteoporotic vertebral fractures with
      regard to pain relief and improvement of the QoL. Even segmental re-alignment can
      be achieved to a certain extent with proper patient positioning.

PMID- 19838344
TI  - Evaluation of hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow
      aspirate as a bone graft substitute for posterolateral spinal fusion.
AB  - BACKGROUND: Autologous cancellous bone is the most effective biological graft
      material. However, harvest of autologous bone is associated with significant
      morbidity. Since porous hydroxyapatite and beta-tricalcium phosphate are
      biodegradable materials and can be replaced by bone tissue, but it lacks
      osteogenic property. We conducted a study to assess their use as a scaffold and
      combine them with bone marrow aspirate for bone regeneration using its osteogenic
      property for posterolateral spinal fusion on one side and autologous bone graft
      on the other side and compare them radiologically in terms of graft incorporation
      and fusion. MATERIALS AND METHODS: Thirty patients with unstable dorsal and
      lumbar spinal injuries who needed posterior stabilization and fusion were
      evaluated in this prospective study from October 2005 to March 2008. The
      posterior stabilization was done using pedicle screw and rod assembly, and fusion
      was done using hydroxyapatite and beta-tricalcium phosphate mixed with bone
      marrow aspirate as a bone graft substitute over one side of spine and autologous
      bone graft obtained from iliac crest over other side of spine. The patients were
      followed up to a minimum of 12 months. Serial radiographs were done at an
      interval of 3, 6, and 12 months and CT scan was done at one year follow-up. Graft
      incorporation and fusion were assessed at each follow-up. The study was subjected
      to statistical analysis using chi-square and kappa test to assess graft
      incorporation and fusion. RESULTS: At the end of the study, radiological graft
      incorporation and fusion was evident in all the patients on the bone graft
      substitute side and in 29 patients on the autologous bone graft side of the spine
      (P > 0.05). One patient showed lucency and breakage of distal pedicle screw in
      autologous bone graft side. The interobserver agreement (kappa) had an average of
      0.72 for graft incorporation, 0.75 for fusion on radiographs, and 0.88 for the CT
      scan findings. CONCLUSION: Hydroxyapatite and beta-tricalcium phosphate mixed
      with bone marrow aspirate seems to be a promising alternative to conventional
      autologous iliac bone graft for posterolateral spinal fusion.

PMID- 19838345
TI  - Single level cervical disc herniation: A questionnaire based study on current
      surgical practices.
AB  - BACKGROUND: Operative procedures like simple discectomy, with or without fusion
      and with or without instrumentation, for single level cervical disc herniation
      causing neck pain or neurological compromise have been described and are largely
      successful. However, there is a debate on definitive criteria to perform fusion
      (with or without instrumentation) for single level cervical disc herniation.
      Hence, we conducted a questionnaire based study to elicit the opinions of
      practicing neurosurgeons. MATERIALS AND METHODS: About 148 neurosurgeons with
      atleast 12 years of operative experience on single level cervical disc
      herniation, utilizing the anterior approach, were enrolled in our study. All
      participating neurosurgeons were asked to complete a practice based
      questionnaire. The responses of 120 neurosurgeons were analysed. RESULTS: The
      mean age of enrolled surgeons was 51 yrs (range 45-73) with mean surgical
      experience of 16.9 yrs (range 12-40 yrs) on single level cervical disc
      herniation. Out of 120 surgeons 10(8%) had 15-25 years experience and always
      preferred fusion with or without instrumentation and six (five per cent with 17
      27 yrs experience had never used fusion techniques. However, 104 (87%) surgeons
      with 12-40 yrs experience had their own criteria based on their experiences for
      performing fusion with graft and instrumentation (FGI), while. 85 (75%) preferred
      auto graft with cage. CONCLUSIONS: Most of surgeons performed FGI before the age
      of 40, but for others, patient criteria such as job (heavier job), physical
      examination (especially myelopathy) and imaging findings (mild degenerative
      changes on X-ray and signal change in the spinal cord on MRI) were considered
      significant for performing FGI.

PMID- 19838346
TI  - Trans-iliac-sacral-iliac-bar procedure to treat insufficiency fractures of the
      sacrum.
AB  - BACKGROUND: Osteoporosis is an increasing problem attributed to the greater
      longevity of the population and the incidence of fractures related to
      osteoporosis. The presence of osteoporotic bone, comorbidities, and functional
      status of the patient require adequate solutions to improve the clinical outcome
      of sacral insufficiency fractures. Conservative treatment by means of prolonged
      bed rest and analgesics are associated with increased risks and complications. A
      sacroplasty significantly improves the functional outcome. We describe the trans
      iliac-sacral-iliac-bar (TISIB) procedure and our clinical experience to treat
      insufficiency fractures of the sacrum. MATERIALS AND METHODS: The records of 19
      consecutive patients with a mean age of 71.7 years (range: 57-82 years) who had
      been managed with a TISIB procedure from 2005 till 2007 were reviewed
      retrospectively. There were 15 females and 4 males. Predisposing factors for
      sacral insufficiency fractures were osteoporosis (n = 12, 63%), radiotherapy (n =
      6, 32%), and rheumatoid arthritis (n =1). Diagnosis with a mean delay of 3.7
      months was mainly made by CT. All patients were preoperatively and at follow-up
      assessed by means of the visual analogue score (VAS), analgesic consumption, and
      the ability to perform activities of daily living (ADLs) using a 5-point pain
      scale: 1, without pain; 2, mild pain; 3, moderate pain; 4, severe pain and, 5
      unable to perform ADLs because of pain. RESULTS: The average duration of
      postoperative follow-up was 9 months (range: 3-24.5 months). No neurological
      complications occurred during the surgery. A postoperative radiographic study
      showed a well-positioned bar in every case. The mean VAS improved 44.7 mm
      (preoperative: 67.8; at follow-up: 23.2). Fifteen patients (79%) consumed
      narcotic analgesics before surgery, and only one (5%) at follow-up; two patients
      (10%) consumed NSAIDS before surgery and three (15%) after. Two patients (10%)
      consumed minor analgesics before, and 11 (58%) after the procedure. Finally, four
      patients (21%) were not taking any analgesics at follow-up. Before surgery, 9
      patients (47%) were able to perform ADLs with a pain score of 4; 6 (32%) with a
      score of 3, and 4 (21%) a score of 2. At follow-up 1 (5%) did have a score of 4;
      1 (5%) a score of 3, 8 (42%) a score of 2 and 9 (47%) a pain score of 1.
      CONCLUSION: A TISIB PROCEDURE RELIES ON THE PRINCIPLES OF FRACTURE TREATMENT:
      fracture stabilisation and compression. The incapacitating problem of an
      insufficiency fracture of the sacrum can be elegantly solved by means of this
      minimally invasive procedure. A near-immediate improvement is noticed when
      looking at the VAS score, analgesics consumption, and the ability to perform
      ADLs.

PMID- 19838347
TI  - Delayed fixation of displaced type II and III pediatric femoral neck fractures.
AB  - BACKGROUND: Time from injury to fixation of femoral neck fractures has been
      postulated as a vital determinant for rate of complications; however, no
      prospective study is available in the English literature. Delay, unfortunately,
      is inevitable in developing countries. The aim of the present study is to
      retrospectively review the outcome after delayed fixation of displaced type II
      and III femoral neck fractures in children. MATERIALS AND METHODS: Using a
      standard assessment chart, we retrospectively reviewed medical records of all
      pediatric patients having femoral neck fractures presenting to our institution
      from June 1999 to May 2006. Inclusion criteria were children between 5 and 15
      years of age sustaining displaced Delbet type II and III femoral neck fractures
      having a complete follow-up of at least 2 years. Patients with known metabolic
      disease, poliomyelitis or cerebral palsy, were excluded from the study. After
      application of inclusion and exclusion criteria, 22 patients having 22 fractures
      (13 type II and 9 type III) were studied. Surgery could be performed after a mean
      delay of 11.22 days (ranging from 2 to 21 days). Closed reduction was achieved in
      14 cases and 8 cases required open reduction through anterolateral approach.
      RESULT: Osteonecrosis was noted in eight patients (36.37%) who included two of
      nine patients (22.22%) operated in the first week, three of eight patients
      (37.51%) operated in the second week, and three of five patients (60%) operated
      in the third week of injury. Nonunion was seen in four (18.18%) cases, and two of
      them were associated with failure of implants. One was treated by valgus
      osteotomy and the other by Meyer's procedure. Fractures united in both children
      but the latter developed avascular necrosis. Functional results, as assessed
      using Ratliff's criteria, were good in 14 (63.63%), fair in 2 (9%), and poor in 6
      (27.27%) patients. CONCLUSION: Delay in fixation, type of fracture, and ability
      to achieve and maintain reduction are factors primarily responsible for the
      outcome. We also found that delay after the first week further adversely affects
      the outcome.

PMID- 19838348
TI  - Prophylactic use of antibiotic-loaded bone cement in primary total knee
      arthroplasty: Justified or not?
AB  - BACKGROUND: The routine use of antibiotic-loaded bone cement (ABLC) during
      primary or uninfected revision arthroplasty remains controversial. Many studies
      quote the total joint arthroplasty (TJA) infection rate to be less than 1%. Total
      knee arthroplasty (TKA) has a higher infection rate than total hip arthroplasty
      (THA). Based on both animal and human studies in the past, ABLC has been found
      effective in reducing the risk of infection in primary TJA. We are presenting
      retrospective analysis of results in terms of infection rate in 659 TKA performed
      by a single surgeon under similar conditions during 2004-2007 using CMW1 (Depuy,
      Leeds, UK) with premixed 1 g of gentamicin. PATIENTS AND METHODS: We did primary
      TKA in 659 knees of 379 patients during 2004-2007 using CMW1 (Depuy, Leeds, UK)
      cement containing 1 g of gentamicin in 40 g of cement in a premixed form.
      Standard OT conditions were maintained using laminar air flow, isolation suits
      for the operating team, pulse lavage and disposable drapes in each patients.
      Midvastus approach was used in all the patients to expose the knee joint. A
      systemic antibiotic (third-generation cephalosporin and aminoglycoside) was used
      preoperatively and 48 h postoperatively. We observed the patients in terms of
      infection in the high-risk and low-risk group till the recent follow-up with a
      mean of 20.6 months (9-38 months). RESULTS: We had deep infection in six knees in
      six patients and all of them required two-stage revision surgery later in the
      high-risk group. Infection occurred at a mean of 20.5 months after surgery
      earliest at 9 months and latest at 36 months after surgery. The infection rate in
      our study was 0.91% which is comparatively less than the reported incidence of 1
      2% in reported studies. CONCLUSION: We conclude that the use of antibiotic loaded
      bone cement is one of the effective means in preventing infection in primary TJA.

PMID- 19838349
TI  - Expandable self-locking nail in the management of closed diaphyseal fractures of
      femur and tibia.
AB  - BACKGROUND: Intramedullary fixation is the treatment of choice for closed
      diaphyseal fractures of femur and tibia. The axial and rotational stability of
      conventional interlocking nails depends primarily on locking screws. This method
      uses increased operating time and increased radiation exposure. An intramedullary
      implant that can minimize these disadvantages is obviously better. Expandable
      intramedullary nail does not rely on interlocking screws and achieves axial and
      rotational stability on hydraulic expansion of the nail. We analyzed 32 simple
      fractures of shaft of femur and tibia treated by self-locking expandable nail.
      MATERIALS AND METHODS: Intramedullary fixation was done by using self-locking,
      expandable nail in 32 patients of closed diaphyseal fractures of tibia (n = 10)
      and femur (n = 22). The various modes of injury were road traffic accidents (n =
      21), fall from height (n = 8), simple fall (n = 2), and pathological fracture (n
      = 1). Among femoral diaphyseal fractures 16 were males and six females, average
      age being 33 yrs (range, 18- 62 yrs). Seventeen patients had AO type A (A1 (n =
      3), A2 (n = 4), A3 (n = 10)) and 5 patients had AO type B (B1 (n = 2), B2 (n =
      2), B3 (n = 1)) fractures. Eight patients having tibial diaphyseal fractures were
      males and two were females; average age was 29.2 (range, 18- 55 yrs). Seven were
      AO type A (A1 (n = 2), A2 (n = 3), A3 (n = 2)) and three were AO type B (B1 (n =
      1), B2 (n = 1), and B3 (n = 1)). We performed closed (n = 27) or open reduction
      (n = 5) and internal fixation with expandable nail to stabilize these fractures.
      The total radiation exposure during surgery was less as no locking screws were
      required. Early mobilisation and weight-bearing was started depending on fracture
      personality and evidences of healing. Absence of localised tenderness and pain on
      walking was considered clinical criteria for union, radiographic criteria of
      union being continuity in at least in three cortices in both AP and lateral
      views. Patients were followed for at least one year. RESULTS: The average
      operative time was 90 min (range, 55-125 min) for femoral fractures and 53 min
      (range, 25-115 min) for tibial fractures. Radiation exposure was minimum, average
      being 84 seconds (range, 54-132) for femoral fractures and 54 seconds (range, 36
      78) for tibial fractures. All fractures healed, but few had complications, such
      as infection (one case with tibial fracture) bent femoral nail with malunion (n =
      1), and delayed union (n = 3; 2 cases in femur and 1 case in tibia). Mean time of
      union was 5.1 months (range, 4-10(1/2) months) for femoral fractures and 4.8
      months (range, 3-9 months) for tibial fractures. CONCLUSION: We found the nail
      very easy to use with effective fixation in AO type A and B fractures in our
      setting. Less surgical time is required with minimum complications. The main
      advantage of the expandable nail is that if affords. satisfactory axial,
      rotatory, and bending stability with decreased radiation exposure to operating
      staff and the patient.

PMID- 19838350
TI  - Operative treatment of intra-articular calcaneal fractures with calcaneal plates
      and its complications.
AB  - BACKGROUND: In a retrospective study we analysed intra-articular calcaneal
      fracture treatment by comparing results and complications related to fracture
      stabilization with nonlocking calcaneal plates and locking compression plates.
      MATERIALS AND METHODS: We performed 76 osteosynthesis (67 patients) of intra
      articular calcaneal fractures using the standard extended lateral approach from
      February 2004 to October 2007. Forty-two operations using nonlocking calcaneal
      plates (group A) were performed during the first three years, and 34 calcaneal
      fractures were stabilized using locking compression plates (group B) in 2007. In
      the Sanders type IV fractures, reconstruction of the calcaneal shape was
      attempted. Depending on the type of late complication, we performed subtalar
      arthroscopy in six cases, arthroscopically assisted subtalar distraction bone
      block arthrodesis in six cases, and plate removal with lateral-wall decompression
      in five cases. The patients were evaluated by the AOFAS Ankle-Hindfoot Scale.
      RESULTS: Wound healing complications were 7/42 (17%) in group A and 1/34 (3%) in
      group B. No patient had deep osseous infection or foot rebound compartment
      syndrome. Preoperative size of Bohler's angle correlated with postoperative
      clinical results in both groups. There were no late complications necessitating
      corrective procedure or arthroscopy until December 2008 in Group B. All late
      complications ccurred in Group A. The overall results according to the AOFAS
      Ankle Hindfoot Scale were good or excellent in 23/42 (55%) in group A and in
      30/34 (85%) in group B. CONCLUSION: Open reduction and internal fixation of intra
      articular calcaneal fractures has become a standard surgical method. Fewer
      complications and better results related to treatment with locking compression
      plates confirmed in comparison to nonlocking ones were noted for all Sanders
      types of intra-articular calcaneal fractures. Age and Sanders type IV fractures
      are not considered to be the contraindications to surgery.

PMID- 19838351
TI  - A prospective study of Japas' osteotomy in paralytic pes cavus deformity in
      adolescent feet.
AB  - BACKGROUND: Pes cavus is a progressive and ugly deformity of the foot. Although
      initially the deformity is painless, with time, painful callosities develop under
      metatarsal heads and arthritis supervenes later in feet. Mild deformities can be
      treated with corrective shoes, or foot exercises. However, in others, operative
      treatment is imperative. Soft tissue operations are largely unsatisfactory and
      temporary. Bony operations give permanent correction. We present our series of 18
      patients of pes cavus in the adolescent age group, treated by Japas' V-osteotomy
      of the tarsus. MATERIALS AND METHODS: 18 patients of paralytic pes cavus
      deformity were treated by Japas osteotomy, between March 1995 and 2005, at our
      institute. The age of the patients ranged from 8.6 to 15 years (mean 11.3); 10
      were boys and 8 girls. All cases had unilateral involvement, and all, but one,
      were post-polio cases. RESULT: The mean follow-up is 5.4 years. Of the 18
      patients, 14 had excellent or good corrections; 4 had poor
      correction/complications. However, those patients could be salvaged by triple
      arthordesis or Dwyer's calcaneal osteotomy. CONCLUSION: Japas' osteotomy is a
      satisfactory option for correction of pes cavus deformity in adolescents. In
      patients who have rigid hind foot equinus or varus, however, the results are
      compromised.

PMID- 19838352
TI  - Type 4 capitellum fractures: Diagnosis and treatment strategies.
AB  - BACKGROUND: Fractures of the capitellum are rare injuries of the elbow usually
      seen in the adolescents. This fracture is often missed in the emergency room if a
      proper radiograph is not available. Recent reports have described many modalities
      of treatment favoring headless screw for fixation. The facility for headless
      screw fixation, however, is not available in most centers. This paper presents
      the diagnosis and management of type 4 capituller fractures (Mckee) with gadgets
      available in a district hospital. MATERIALS AND METHODS: Between 2004 and 2007
      three patients with right sided type IV capetullar fracture were treated in a
      district hospital. There were two boys aged 15 and 17 and one 33 years old lady.
      In one case, the fracture was missed in the emergency room. A double arc sign in
      the lateral views of the X-rays of the elbow was seen in all the cases. In each
      case a preoperative CT scan was done and a diagnosis of Mckee type IV fracture of
      the capitellum was made. Under tourniquet, using extended lateral approach, open
      reduction and internal fixation was done using 4mm partially threaded AO
      cancellous screws (n=2) and 2.7 mm AO screws (n=1), under vision from posterior
      to anterior direction from the posterior aspect of lateral condyle of humerus
      avoiding articular penetration. RESULTS: All the fractures united uneventfully.
      At the end of one year follow-up, two cases had excellent elbow function;
      implants were removed and there were no signs of AVN or arthritis. The third case
      had good elbow ROM at 11 months without AVN. CONCLUSION: Double arc sign on
      lateral X-rays of the elbow along with pre-operative CT scan evaluation is
      important to avoid a missed diagnosis and analysis of type IV capitellur
      fracture. Fixation with non-cannulated ordinary AO screws using extended Kocher's
      lateral approach has given good results.

PMID- 19838353
TI  - Management of radial clubhand with gradual distraction followed by
      centralization.
AB  - BACKGROUND: Treatment of radial clubhand has progressed over the years from no
      treatment to aggressive surgical correction. Various surgical methods of
      correction have been described; Centralization of the carpus over the distal end
      of the ulna has become the method of choice. Corrective casting prior to
      centralization is an easy and effective method of obtaining soft tissue
      stretching before any definitive procedure is undertaken. Moreover, it helps put
      the limb in a correct position. The outcome of deformity correction by serial
      casting / JESS distractor followed by centralization is discussed. MATERIALS AND
      METHODS: In a prospective study, of 17 cases with 18 radial clubhands of Heikel's
      Grade III and IV (with average age 11 months (range 20 days - 24 months) with M:F
      of 2.6:1, were treated by gradual soft tissue stretching using corrective cast
      (14 cases) and JESS distraction (4 cases), followed by centralization (16 cases)
      or radialization (2 cases) and tendon transfers. RESULTS: The average correction
      attained during the study was 71 degrees of radial deviation and 31 degrees of
      volar flexion. The average third metacarpal to distal ulna angle in
      anteroposterior and lateral view at final follow-up was 7 degrees in both views.
      Angle of movement at elbow showed a small increase from 99 degrees to 101 degrees
      during the follow-up period. However, the range of movement at fingers showed
      increase in stiffness during the follow-up. No injury occurred to the distal
      ulnar epiphysis during the operative intervention. The results at the final
      follow-up, at the end of 2 years were graded on the basis of the criteria of F.W.
      Bora, and of Bayne and Klug. Considering the criteria of F.W. Bora, satisfactory
      result was shown by nine of the 18 hands (50%) while 16 out of 18 hands (89%)
      showed good or satisfactory result based on deformity criteria of Bayne and Klug.
      CONCLUSION: The management of radial clubhand by gradual corrective cast or JESS
      distractor followed by centralization and tendon transfers in children is an
      acceptable method of treatment with consistently satisfactory results, both
      functional and cosmetic.

PMID- 19838354
TI  - Migrating transient osteoporosis of the hip in a 30-year-old man.
AB  - Transient osteoporosis of hip is a condition of unknown etiology, presenting as
      painful limping, and characterized by osteopenia of the involved joint without
      preexisting disease or immobilization. Most of the cases were reported in middle
      aged men, and one-third of the cases develop in women in the third trimester of
      pregnancy. The hypothesis that this condition leads to avascular necrosis of the
      hip has been disproved by various reports and hence does not warrant any surgical
      interference. This is a self limiting condition, which needs regular follow-up.
      The authors report a case of migrating transient osteoporosis of the hip in a 30
      year-old man successfully treated with antiresorptive treatment.

PMID- 19838355
TI  - Unilateral ossified ligamentum flavum in the high cervical spine causing
      myelopathy.
AB  - High cervical ossified ligamentum flavum (OLF) is rare and may cause progressive
      quadriparesis and respiratory failure. Our two patients had unilateral OLF
      between C1 and C4 levels. MR showed a unilateral, triangular bony excrescence
      with low signal and a central, intermediate or high signal on all pulse sequences
      due to bone marrow within. There was Type I thecal compression (partial deficit
      of contrast media ring). The first patient had a linear and nodular OLF with
      calcification within tectorial membrane, C2-3 fusion and unilateral C2-facetal
      hypertrophy; and the second patient, a lateral, linear OLF with loss of lordosis
      and C3-6 spondylotic changes. A decompressive laminectomy using "posterior
      floating and enbloc resection" brought significant relief in myelopathy.
      Histopathology showed mature bony trabeculae, bone marrow and ligament tissue.
      The coexisting mobile cervical vertebral segment above and congenitally fused or
      spondylotic rigid segment below the level of LF may have led to abnormal strain
      patterns within resulting in its unilateral ossification. In dealing with
      cervical OLF, carefully preserving facets during laminectomy or laminoplasty
      helps in maintaining normal cervical spinal curvature.

PMID- 19838356
TI  - Cauda equina syndrome: A rare complication in intensive care.
AB  - A 73-year-old married retired woman with a history of myocardial infarction and
      primary biliary cirrhosis was admitted to intensive care unit with complaints of
      chest pain. She was suspected to have pulmonary embolism (PE) and was treated
      with low-molecular-weight heparin (LMWH) and aspirin. She had computerized
      tomographic pulmonary angiography on next day, which ruled out any evidence of
      PE, until she was continued on LMWH. Three days later, she developed progressive
      right leg weakness and loss of sphincter control and patchy loss of sensation
      from T10 and below. She was seen by neurologist and had an MRI scan, which showed
      extensive subdural clot compressing the conus and lower half of the thoracic
      cord. She underwent T9-L1, L3, L5-S1 laminectomies, and evacuation and
      decompression of the clot. She showed very slight recovery following the surgery
      and left with residual paraparesis. This case is reported to raise awareness
      among intensivists to be cautious in establishing the diagnosis before
      prescribing the LMWH and be vigilant to diagnose cauda equina syndrome and treat
      promptly to avoid residual neurological problems.

PMID- 19838357
TI  - Bone stimulators: Beyond the black box.

PMID- 19838359
TI  - Bone stimulation for fracture healing: What's all the fuss?
AB  - Approximately 10% of the 7.9 million annual fracture patients in the United
      States experience nonunion and/or delayed unions, which have a substantial
      economic and quality of life impact. A variety of devices are being marketed
      under the name of "bone growth stimulators." This article provides an overview of
      electrical and electromagnetic stimulation, ultrasound, and extracorporeal shock
      waves. More research is needed for knowledge of appropriate device
      configurations, advancement in the field, and encouragement in the initiation of
      new trials, particularly large multicenter trials and randomized control trials
      that have standardized device and protocol methods.

PMID- 19838358
TI  - Global burden of trauma: Need for effective fracture therapies.
AB  - Orthopedic trauma care and fracture management have advanced significantly over
      the last 50 years. New developments in the biology and biomechanics of the
      musculoskeletal system, fixation devices, and soft tissue management have greatly
      influenced our ability to care for musculoskeletal injuries. Many therapies and
      treatment modalities have the potential to transform future orthopedic treatment
      by decreasing invasive procedures and providing shorter healing times. Promising
      results in experimental models have led to an increase in clinical application of
      these therapies in human subjects. However, for many modalities, precise clinical
      indications, timing, dosage, and mode of action still need to be clearly defined.
      In order to further develop fracture management strategies, predict outcomes and
      improve clinical application of newer technologies, further research studies are
      needed. Together with evolving new therapies, the strategies to improve fracture
      care should focus on cost effectiveness. This is a great opportunity for the
      global orthopedic community, in association with other stakeholders, to address
      the many barriers to the delivery of safe, timely, and effective care for
      patients with musculoskeletal injuries in developing countries.

PMID- 19838360
TI  - The science of electrical stimulation therapy for fracture healing.
AB  - This article is a brief review of the basic science research conducted in the
      field of electrical stimulation for fracture healing. Direct electrical current,
      capacitive coupling, and inductive coupling have been studied as potential
      techniques to enhance fracture healing through the proliferation and
      differentiation of osteogenic cells. These techniques are particularly appealing
      as they offer a potential minimally invasive solution to the difficult clinical
      problem of delayed fracture healing and nonunion. Basic science studies have
      shown conclusively that electrical stimulation techniques lead to bone cell
      proliferation and have attempted to elucidate the intracellular processes by
      which this bone cell proliferation occurs. Further basic science and clinical
      research is required to enhance the effectiveness of this therapy for the
      treatment of fracture nonunions.

PMID- 19838361
TI  - Low-intensity pulsed ultrasound: Fracture healing.
AB  - Annually, millions of people across the world are inflicted with bone fracture
      injuries. Untimely healing is a significant burden in terms of socioeconomic
      costs, personal costs, and patients' quality of life. Low-intensity pulsed
      ultrasound (LIPUS) has gained much attention as a potential adjunctive therapy
      for accelerating fresh fracture healing, but its efficacy remains controversial.
      This paper is presented in two parts a literature review followed by a systematic
      review. The literature review highlights the physiology of fracture healing and
      the influence LIPUS exerts on cells and molecules involved in this healing
      process. In part two, we present a systematic review of randomized controlled
      trials (RCTs) assessing the clinical effectiveness of LIPUS in accelerating the
      time to fracture healing. The electronic databases we searched for the systematic
      review are as follows: MEDLINE (from 1996 to November 2008), EMBASE (from 1996 to
      November 2008), and Healthstar (from 1966 to October 2008). A two-step screening
      process was used to assess the eligibility of studies yielded by our search. The
      first step was a review of titles and abstracts for the selection of studies that
      met the following criteria: (i) inclusion of skeletally mature patients with a
      fresh fracture, (ii) a minimum of two treatment arms with at least one arm
      receiving LIPUS treatment and another arm receiving placebo, (iii) random
      allocation of patients to the different treatment arms, (iv) radiological
      assessment of time to fracture healing, and (v) publication in the English
      language. In the second step, selected articles were reviewed in full text.
      Eligible trials were all scored independently by two reviewers for methodological
      reporting quality using the 15-item CLEAR NPT checklist (Checklist to Evaluate
      the Report of a Nonpharmacological Trial). We identified a total of seventy seven
      studies, nine of which met our inclusion criteria after the initial screening. Of
      these nine trials, seven were included for the final review. The types of
      fractures studied among these seven trials included lateral malleolar, radial,
      and tibial fractures. Three of the seven trials found that LIPUS significantly
      reduces healing time compared to placebo, whereas the other four did not find a
      statistically significant difference. There is a substantial level of
      inconsistency in the findings of several RCTs evaluating the efficacy of LIPUS as
      an adjunct for fracture healing. Although LIPUS has proven to be effective in
      certain trials for accelerating fracture healing, no definitive statement can be
      made regarding its universal use for all fracture types and methods of fracture
      care. Future high-quality RCTs with larger sample sizes may help to elucidate the
      specific indications that warrant or dismiss the need for LIPUS therapy.

PMID- 19838362
TI  - Low-intensity pulsed ultrasound: Nonunions.
AB  - Nonunions occur in 5-10% of fractures and are characterized by the failure to
      heal without further intervention. Low intensity pulsed ultrasound therapy has
      been developed as an alternative to surgery in the treatment of nonunions. We
      describe a systematic review on trials of low-intensity pulsed ultrasound therapy
      for healing of nonunions. We searched the electronic databases Medline and the
      Cochrane library for articles on ultrasound and healing of nonunions published up
      to 2008. Trials selected for the review met the following criteria: treatment of
      at least one intervention group with low intensity pulsed ultrasound; inclusion
      of patients (humans) with one or more nonunions (defined as "established" or as a
      failure to heal for a minimum of eight months after initial injury); and
      assessment of healing and time to healing, as determined radiographically. The
      following data were abstracted from the included studies: sample size, ultrasound
      treatment characteristics, nonunion location, healing rate, time to fracture
      healing, fracture age, and demographic information. We found 79 potentially
      eligible publications, of which 14 met our inclusion criteria. Of these, eight
      studies were used for data abstraction. Healing rates averaged 87%, (range 65.6%
      100%) among eight trials. Mean time to healing was 146.5 days, (range 56-219
      days). There is evidence from trials that low-intensity pulsed ultrasound may be
      an effective treatment for healing of nonunions. More homogeneous and larger
      controlled series are needed to further investigate its efficacy.

PMID- 19838363
TI  - Electrical stimulation: Nonunions.
AB  - The current paper attempts to provide an overview on the currently available
      fundamental, preclinical, and clinical evidence on the biologic rationale and
      therapeutic efficacy of electrical stimulation devices applied in patients with
      long-bone nonunions. Electrical stimulation (ES) involves the generation of an
      electrical or electromagnetic current through the ununited fracture. Such
      currents, which are present in physiologically healing bone, provide stimuli that
      favor a healing response to bone cells. These stimuli include the enhancement of
      transmembrane and intracellular calcium-mediated signal transduction and an
      increased synthesis of paracrine and autocrine growth factors by osteoblasts.
      Favorable healing union rates, ranging from 43% to 90%, as found by several
      clinical case series, have prompted the orthopedic community to, at least
      partially, adopt ES for the treatment of long bone nonunions. Nonetheless,
      randomized controlled trials have not provided definitive evidence of ES causing
      nonunions to heal more often than sham devices. This impediment is probably
      formed by small sample sizes, lack of consistency regarding the definition of
      union and nonunion, and variability in ES current used.

PMID- 19838364
TI  - Pulsed electromagnetic stimulation in nonunion of tibial diaphyseal fractures.
AB  - BACKGROUND: Nonunion of long bones is a difficult clinical problem and challenges
      the clinical acumen of surgeons. Multiple surgical or nonsurgical modalities have
      been used to treat nonunions. Noninvasive pulsed electromagnetic stimulation is
      an entity known to affect the piezoelectric phenomenon of bone forming cells. We
      conducted a study on 45 long-bone fractures of tibia treated by pulsed
      electromagnetic stimulation, which are analyzed and reported. MATERIALS AND
      METHODS: A total of 45 tibial fractures with established atrophic nonunion were
      enrolled between 1981 and 1988. All the patients had abnormal mobility and no or
      minimal gap at fracture site with no evidence of callus formation across the
      fracture site. The patients' age ranged between 24 and 68 years; 40 were men and
      5 were women. All patients having evidence of infection, implant in situ, and gap
      nonunions were excluded from study. Pulsed electromagnetic stimulation was given
      using above-knee plaster of Paris cast (0.008 Weber/m2 magnetic field was created
      for 12 h/day). The average duration for pulsed electromagnetic stimulation (PEMS)
      therapy was 8.35 weeks, with the range being 6-12 weeks. The cases were evaluated
      at 6 weeks and subsequently every 6-weekly interval for clinical and radiological
      union. The withdrawal of therapy was decided as per clinicoradiological evidence
      of union. RESULTS: All but three patients showed evidence of union. About 35% (n
      = 16) cases showed union in 10 weeks, and 85%(n = 38) cases showed union in 4
      months. The average duration of therapy using PEMS was 8.35+/-0.48 weeks, and the
      average duration of immobilization was 3.02 +/- 0.22 months. Three cases that did
      not show evidence of union were poorly compliant for the apparatus of PEMS.
      CONCLUSION: PEMS is a useful noninvasive modality of treatment for difficult
      nonunion of long bones.

PMID- 19838365
TI  - Extracorporeal shockwave therapy: A systematic review of its use in fracture
      management.
AB  - Extracorporeal shockwave therapy is increasingly used as an adjuvant therapy in
      the management of nonunions, delayed unions and more recently fresh fractures.
      This is in an effort to increase union rates or obtain unions when fractures have
      proven recalcitrant to healing. In this report we have systematically reviewed
      the English language literature to attempt to determine the potential clinical
      efficacy of extracorporeal shockwave therapy in fracture management. Of 32
      potentially eligible studies identified, 10 were included that assessed the
      extracorporeal shockwave therapy use for healing nonunions or delayed unions, and
      one trial was included that assessed its use for acute high-energy fractures.
      From the included, studies' overall union rates were in favor of extracorporeal
      shockwave therapy (72% union rate overall for nonunions or delayed unions, and a
      46% relative risk reduction in nonunions when it is used for acute high-energy
      fractures). However, the methodologic quality of included studies was weak and
      any clinical inferences made from these data should be interpreted with caution.
      Further research in this area in the form of a large-scale randomized trial is
      necessary to better answer the question of the effectiveness of extracorporeal
      shockwave therapy on union rates for both nonunions and acute fractures.

PMID- 19838366
TI  - Economic evaluation of bone stimulation modalities: A systematic review of the
      literature.
AB  - Various bone stimulation modalities are commonly used in treatment of fresh
      fractures and nonunions; however, the effectiveness and efficiency of these
      modalities remain uncertain. A systematic review of trials evaluating the
      clinical and economical outcomes of ultrasounds, electrical stimulation, and
      extracorporeal sound waves on fracture healing was conducted. We searched four
      electronic databases for economic evaluations that assessed bone stimulation
      modalities using ultrasound therapy, electrical stimulation, or extracorporeal
      shock waves. In addition, we searched the references and related articles of
      eligible studies, and a content expert was contacted. Information on the clinical
      and economical outcomes of patients was independently extracted by reviewers.
      Fourteen studies met the inclusion criteria; therefore, very limited research was
      found on the cost associated with treatments and the corresponding outcomes. The
      data available focus primarily on the efficacy of newly introduced treatment
      methods for bone growth, but failed to incorporate the costs of implementing such
      treatments. One economic analysis was identified that assessed different
      treatment paths using ultrasound. A total cost savings of 24-40% per patient
      occurred when ultrasound was used for fresh fractures and nonunions (grade C
      recommendation). The results suggest that the ultrasound is a viable alternative
      for bone stimulation; however, the impacts of the other modalities are left
      unknown due to the lack of research available. Methodological limitations leave
      the overall economic and clinical impact of these modalities uncertain. Large,
      prospective, randomized controlled trials that include cost-effectiveness
      analyses are needed to further define the clinical effectiveness and financial
      burden associated with bone stimulation modalities.

PMID- 19838367
TI  - Fracture healing in India: Available therapies, indications, and protocols.
AB  - The availability of fracture healing therapies to the general public is limited
      in India. The infrastructure of the health system in India, involving both public
      and private sectors, does not provide adequate opportunity for rural and low
      income inhabitants to access needed care. Also the lack of funding from the
      government and the overall lack of physicians place a large strain on the system.
      This paper will take an in-depth look at the state of the current health care
      system and how it affects bone stimulation therapy in India. The Indian Journal
      of Orthopaedics was used as a reference for the bone stimulation therapies
      currently utilized in India. A general search of the therapies and technologies
      was performed to determine protocols and indications. A table of fracture healing
      therapies and technologies was composed which provides a description of each
      therapy, as well as its specific indications and protocols. This information was
      then used by the authors to hypothesize the most feasible methods of fracture
      healing to meet the Indian demographic. Based on an assessment of the health
      system of India, the most practical methods of bone stimulation therapy were
      determined. It was also determined that nearly all forms of therapy could be made
      available if sufficient resources were set aside for it. Bone stimulation therapy
      in India remains a large void in the health care system.

PMID- 19838368
TI  - Dynamic osteosynthesis by modified Kuntscher nail for the treatment of tibial
      diaphyseal fractures.
AB  - BACKGROUND: We evaluated a series of diaphyseal fractures of the tibia using low
      cost, Indian-made modified Kuntscher nail (Daga nail) with the provision of
      distal locking screw for the management of the tibial diaphyseal fractures.
      MATERIALS AND METHODS: One hundred and fifty one consecutive patients with
      diaphyseal fractures of tibia with 151 fractures who were treated by Daga nail
      were enrolled. One of the patients who had died because of cancer, and the two
      patients who were lost to follow-up at 3 months were excluded from the
      study.Therefore data of 148 patients with one hundred and fortyeight fractures is
      described. One hundred twenty closed fractures, 20 open Grade I fractures, and
      eight open Grade II fractures as per Gustilo and Anderson classification were
      included in this study. One hundred fourteen men and 34 women, with a mean age of
      38.4 years, were studied. The result were analysed for Surgical time, duration of
      hospitalisation, union time, union rate, complication rate, functional recovery
      and crutch walking time. The fractures were followed at least until the time of
      solid union. RESULTS: The follow-up period averaged 15 months (range, 6-26
      months). Union occurred in 140 cases (94.6%). The mean time to union was 13 weeks
      for closed fractures,17.8 weeks for Grade I open fractures, and 21.6 weeks for
      Grade II open fractures. Compartment syndrome occurred in two patients.
      Superficial infection occurred in five cases of Grade I and II compound
      fractures. Three closed fractures and one case of Grade I compound fracture
      required bone grafting for delayed union. Two cases of Grade II compound fracture
      with nonunion required revision surgery and bone grafting. Twelve cases resulted
      in acceptable malalignment due to operative technical error. In four cases, the
      distal screw breakage was seen, but none of these complications interfered with
      fracture healing. Recovery of joint motion was essentially normal in those
      patients without knee or ankle injury. CONCLUSION: Unreamed distally locked
      dynamic tibial nailing (modified Kuntscher nail/Daga nail) can produce excellent
      clinical results for diaphyseal tibial fractures. It has the advantages of
      technical simplicity, minimal cost, user-friendly instrumentation, and a short
      learning curve.

PMID- 19838369
TI  - Distraction histiogenesis for treatment of Kienbock's disease: A 2- to 8-year
      follow-up.
AB  - BACKGROUND: Distraction histiogenesis is known to enhance vascularity and
      stimulate new tissue formation. Its use in Kienbock's disease is not reported in
      the literature, so we proposed to study the outcome after distraction
      histiogenesis in treating this condition. MATERIALS AND METHODS: This prospective
      study comprised of six patients (two male and four female) with mean age 18.16
      years (range 21-35 years) with clinicoradiologically diagnosed Lichtman stage II
      (n = 3) and stage III (n = 3) Kienbock's disease with a mean duration of symptoms
      6.67 months. The ulnar variance was neutral in two and was negative in four
      patients treated with the application of Joshi external stabilization system
      (JESS) across the wrist. The gradual distraction was done at a rate of 0.5
      mm/day. After the distraction of 5-7 mm, the distractors were kept static for 3
      weeks. The wrist was mobilized by using hinged distractors for next 3 weeks.
      Later short cockup splint was used for further 4 weeks. At the end of minimum 2
      years, an assessment was done on the basis of relief of symptoms, ability to
      perform activities of daily living, range of movement at wrist, grip strength,
      and on radiology (change in the density of bone and C:MC ratio i.e ratio of
      carpal height to third metacarpal height). RESULTS: The mean follow-up was of 4.5
      years (range 2-8 years). The average duration of treatment was 5.3 months (range
      4.5-6 months), and the duration of distraction (both static and hinged) was 8
      weeks. Clinically all the patients were relieved of the symptoms with an increase
      in the range of wrist movement (ulnar deviation increased from 20.8 degrees to
      29.5 degrees , radial deviation from 17.5 degrees to 21 degrees , dorsiflexion
      from 37.5 degrees to 52.5 degrees , and palmer flexion from 38.3 degrees to 47.5
      degrees ). At the last follow-up, activities of daily living were not affected,
      and all the patients were on their previous jobs without any fresh complaints.
      The average grip strength increased to 73-86% of normal. Radiologically the C:MC
      ratio (ratio of carpal height to third metacarpal height) did not show any
      significant improvement, but the density of lunate decreased. CONCLUSION:
      Distraction histiogenesis when used in Lichtman stage II and III with negative or
      neutral ulnar variance gives good symptomatic relief, allowing return to normal
      activities. This study has also shown that reparative process is possible in
      avascular bone by distraction. The authors recommend further research in this
      modality of treatment.

PMID- 19838370
TI  - Molecular studies of achondroplasia.
AB  - BACKGROUND: Achondroplasia (ACH) is the most frequent form of short-limbed
      dwarfism, caused by mutations in the FGFR3 gene. It follows an autosomal dominant
      inheritance, though most cases are sporadic. The molecular techniques are the
      only available methods to confirm the diagnosis of a skeletal dysplasia. Clinical
      and radiological features are only suggestive and not confirmatory. The present
      study was conducted to find out how often the clinical diagnosis of
      achondroplasia is verified on molecular studies. MATERIALS AND METHODS: From 1998
      through 2007, we carried out molecular analysis for the two common mutations in
      the FGFR3 gene in 130 cases clinically suspected to have ACH. RESULTS: A
      diagnostic mutation was identified in 53 (40.8%) cases. The common mutation
      (1138G>A) was present in 50 (94.7%) of the positive cases, while the rare 1138
      G>C substitution was found in three (5.3%). CONCLUSION: This study shows that
      confirmation of clinical diagnosis of ACH by molecular genetic testing is
      essential to distinguish it from other skeletal dysplasias, to plan therapeutic
      options, and to offer genetic counseling. Management (medical and surgical) in
      patients confirmed to have ACH, is briefly discussed.

PMID- 19838371
TI  - The effect of postoperative immobilization on short-segment fixation without bone
      grafting for unstable fractures of thoracolumbar spine.
AB  - BACKGROUND: Controversy regarding the fixation level for the management of
      unstable thoracolumbar spine fractures exists. Often poor results are reported
      with short-segment fixation. The present study is undertaken to compare the
      effect of fixation level and variable duration of postoperative immobilization on
      the outcome of unstable thoracolumbar burst fractures treated by posterior
      stabilization without bone grafting. PATIENTS AND METHODS: A randomized,
      prospective, and consecutive series was conducted at a tertiary level medical
      center. Thirty-six neurologically intact (Frankel type E) thoracolumbar burst
      fracture patients admitted at our institute between February 2003 and December
      2005 were randomly divided into three groups. Group I (n = 15) and II (n = 11)
      patients were treated by short-segment fixation, while Group III (n = 10)
      patients were treated by long-segment fixation. In Group I ambulation was delayed
      to 10th-14th postoperative day, while group II and III patients were mobilized on
      third postoperative day. Anterior body height loss (ABHL) percentage and increase
      in kyphosis as measured by Cobb's angle were calculated preoperatively,
      postoperatively, and at follow-up. Denis Pain Scale and Work Scales were obtained
      during follow-up. RESULTS: Mean follow-up was 13.7 months (range 3-27 months). At
      the final follow-up the mean ABHL was 4.73% in group I compared with 16.2% in
      group II and 6.20% in group III. The mean Cobb's angle loss was 1.8 degrees in
      group I compared with 5.91 degrees in group II and 2.3 degrees in group III. The
      ABHL difference between groups I and II was significant (P = 0.0002), while
      between groups I and III was not significant (P = 0.49). CONCLUSION: The short
      segment fixation with amenable delayed ambulation is a valid option for the
      management of thoracolumbar burst fractures, as radiological results are
      comparable to that of long-segment fixation with the advantage of preserving
      maximum number of motion segments.

PMID- 19838372
TI  - Functional outcome of corpectomy in cervical spondylotic myelopathy.
AB  - BACKGROUND: Cervical spondylotic myelopathy (CSM) is serious consequence of
      cervical intervertebral disk degeneration. Morbidity ranges from chronic neck
      pain, radicular pain, headache, myelopathy leading to weakness, and impaired fine
      motor coordination to quadriparesis and/or sphincter dysfunction. Surgical
      treatment remains the mainstay of treatment once myelopathy develops. Compared to
      more conventional surgical techniques for spinal cord decompression, such as
      anterior cervical discectomy and fusion, laminectomy, and laminoplasty, patients
      treated with corpectomy have better neurological recovery, less axial neck pain,
      and lower incidences of postoperative loss of sagittal plane alignment. The
      objective of this study was to analyze the outcome of corpectomy in cervical
      spondylotic myelopathy, to assess their improvement of symptoms, and to highlight
      complications of the procedure. MATERIALS AND METHODS: Twenty-four patients
      underwent cervical corpectomy for cervical spondylotic myelopathy during June
      1999 to July 2005.The anterior approach was used. Each patient was graded
      according to the Nuricks Grade (1972) and the modified Japanese Orthopaedic
      Association (mJOA) Scale (1991), and the recovery rate was calculated. RESULTS:
      Preoperative patients had a mean Nurick's grade of 3.83, which was 1.67
      postoperatively. Preoperative patients had a mean mJOA score of 9.67, whereas
      postoperatively it was 14.50. The mean recovery rate of patients postoperatively
      was 62.35% at a mean follow-up of 1 year (range, 8 months to 5 years).The
      complications included one case (4.17%) of radiculopathy, two cases (8.33%) of
      graft displacement, and two cases (8.33%) of screw back out/failure. CONCLUSIONS:
      Cervical corpectomy is a reliable and rewarding procedure for CSM, with
      functional improvement in most patients.

PMID- 19838373
TI  - Disc prolapse and cord contusion in a case of Klippel-Feil syndrome following
      minor trauma.
AB  - Klippel-Feil syndrome (KFS) is defined as congenital fusion of two or more
      cervical vertebrae and patients with KFS are frequently asymptomatic. However,
      these patients are especially prone to cervical cord injury after a minor fall or
      a major traumatic episode. We report an unusual case of KFS where the patient had
      disc prolapse between two Klippel-Feil segments and discuss the difficulties in
      the management of this case.

PMID- 19838374
TI  - Neglected dorsal dislocation of the scaphoid.
AB  - Isolated dislocation of the scaphoid is very rare. A 45-year old male, industrial
      worker reported two and half months after injury with wrist pain and swelling on
      the dorsum of left wrist. He was diagnosed as neglected dorsal dislocation of
      scaphoid. Proximal row carpectomy with capsular interposition was done
      stabilizing the distal carpus on the radius using Kirschner wires. At-12 months
      follow-up the patient had good wrist function and was satisfied with the outcome
      of the treatment. We hereby report this neglected dorsal dislocation of scaphoid
      in view of rarity and discuss the various options for management.

PMID- 19838375
TI  - Primary aneurysmal bone cyst of patella.
AB  - Of all the aneurysmal bone cysts (ABC) occurring in the body, less than 1% are
      seen in the patella. We report here, a 27-year-old woman with Stage III ABC of
      patella. Curettage, chemical and thermal cautery of the bed followed by
      autogenous bone grafting of the defect was done. At two-year follow up, there was
      a suspicion of lucency in the middle of the patella. However a repeat curettage
      revealed only fibrous tissue. Now at four years of follow up, the bone graft
      remained well incorporated. Patient has mild anterior knee pain on stair climbing
      but regained normal knee function.

PMID- 19838376
TI  - Acetabular revision using a total acetabular allograft.
AB  - The most challenging aspect of an acetabular revision is the management of severe
      bone loss, which compromises implant fixation and stability. We present a case of
      failed acetabular revision with extensive bone loss (Paprosky Type 3b) in a 50
      year-old woman with rheumatoid arthritis, which was treated using total
      acetabular allograft. At a follow-up of 1 year and 3 months, the allograft had
      united with the host bone. This is the first report of the use of a total
      acetabular allograft for revision total hip arthroplasty in India. The total
      acetabular allograft allows the placement of the component closer to the normal
      hip center, provides initial stability for the acetabular component, and restores
      bone stock to the host pelvis.

PMID- 19838377
TI  - Research in orthopedics: A necessity.

PMID- 19838378
TI  - Basic research in orthopedic surgery: Current trends and future directions.

PMID- 19838380
TI  - Basic research in orthopedics: India.

PMID- 19838379
TI  - Basic research in orthopedics: South Africa.

PMID- 19838381
TI  - Effect of amino acids lysine and arginine on fracture healing in rabbits: A
      radiological and histomorphological analysis.
AB  - BACKGROUND: Amino acids like arginine and lysine have been suggested to hasten
      the process of fracture healing by improving the local blood supply,
      supplementing growth factors, and improving collagen synthesis. We studied the
      role of lysine and arginine in the fracture repair process with regard to the
      rate of healing, probable mechanisms involved in the process, and mutual
      synergism between these agents. MATERIALS AND METHODS: In an experimental study,
      40 rabbits were subjected to ulnar osteotomy. They were distributed in control
      (14) and test groups (26). Twenty-six animals in the test group were fed with a
      diet rich in lysine and arginine. Both the groups were followed radiologically
      and histologically till union. RESULTS: There was better healing of osteotomy in
      terms of better vascularization, callus formation, and mineralization in the test
      group. The time of healing in the test group was reduced by a period of 2 weeks.
      CONCLUSION: We conclude that amino acids like arginine and lysine may hasten
      fracture healing.

PMID- 19838382
TI  - Transplantation of free tibial periosteal grafts for the repair of articular
      cartilage defect: An experimental study.
AB  - BACKGROUND: Articular chondrocytes have got a long lifespan but rarely divides
      after maturity. Thus, an articular cartilage has a limited capacity for repair.
      Periosteal grafts have chondrogenic potential and have been used to repair
      defects in the articular cartilage. The purpose of the present study is to
      investigate the differentiation of free periosteal grafts in the patellofemoral
      joint where the cambium layer faces the subchondral bone and to investigate the
      applicability of periosteal grafts in the reconstruction of articular surfaces.
      MATERIALS AND METHODS: The study was carried out over a period of 1 year on 25
      adult, male Indian rabbits after obtaining permission from the institutional
      animal ethical committee. A full-thickness osteochondral defect was created by
      shaving off the whole articular cartilage of the patella of the left knee. The
      defect thus created was grafted with free periosteal graft. The patella of the
      right knee was taken as a control where no grafting was done after shaving off
      the articular cartilage. The first animal was used to study the normal histology
      of the patellar articular cartilage and periosteum obtained from the medial
      surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each
      at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular
      surfaces were examined macroscopically and histologically. RESULTS: The grafts
      got adherent to the underlying patellar articular surface at the end of 4 weeks.
      Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal
      cells of the cambium layer were seen differentiating into chondrocytes by the end
      of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner.
      Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks,
      one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had
      columnar formation of cells. Same percentage was maintained at 32 weeks. Four
      grafts (100%) at 48 weeks showed columnar orientation. The control side showed no
      changes over the shaved off articular surface in all the rabbits. One rabbit at 4
      weeks had a dislocation of the patella on the control side. None of the rabbits
      developed any infection or wound dehiscence. CONCLUSION: Autologous periosteal
      graft transplantation can be a promising substitute for articular cartilaginous
      defects.

PMID- 19838383
TI  - Correlation of the SLAP lesion with lesions of the medial sheath of the biceps
      tendon and intra-articular subscapularis tendon.
AB  - BACKGROUND: Superior labral anterior to posterior (SLAP) lesions have been well
      described in the literature and are thought to be secondary to traction injuries
      to the biceps anchor and/or falls on the outstretched arm. The pulley has
      recently been described as a structure that aids in the prevention of biceps
      instability. The intra-articular subscapularis insertion (IASS) has been noted to
      contribute to the robust nature of the medial sheath. The purpose of the study
      was to determine a potential correlation of SLAP lesions and pulley lesions
      with/without IASS lesions, (hereafter referred to as medial sheath) as forces
      that can disrupt the biceps anchor and may also disrupt structures of the medial
      sheath or vice-versa. MATERIALS AND METHODS: Three hundred and sixteen
      consecutive shoulder arthroscopies performed by one surgeon were reviewed
      retrospectively. Operative reports and arthroscopic pictures were carefully
      reviewed with particular attention paid to the labral and pulley pathology.
      Selection bias was noted as the author had never operated primarily for a Type 1
      SLAP lesion. Following, however, and as such, the exclusion criteria, was a Type
      1 SLAP. RESULTS: There were a total of 30 SLAP lesions and a total of 126 medial
      sheath lesions. There were 13 patients who had both SLAP and medial sheath
      lesions. There were 17 patients who had a SLAP lesion without a medial sheath
      lesion. There were 96 medial sheath lesions without a SLAP. A comparison of rates
      between patients who had a medial sheath lesion with a SLAP and those who had a
      medial sheath lesion without a SLAP, for the 316 patients, and when tested with a
      Fisher exact test revealed that there was no statistical significance, P = 0.673.
      The prevalence of SLAP lesions in this population of 316 patients was 9.4%,
      Buford 1%, medial sheath lesions 39%, and SLAP and medial sheath lesions 4%.
      Interestingly, there were three Buford complexes, all associated with a SLAP and
      one Buford complex was associated with both a SLAP and a pulley. When looking at
      the rate for medial sheath lesions when restricted to patients with SLAP lesions,
      the medial sheath lesion rate was 43.3% (13/30; 95% confidence interval 19.6
      66.9%). The medial sheath lesion rate for patients with SLAP lesions differs from
      a rate of zero and is statistically significant, with a P value <0.05. In other
      words, when a SLAP lesion is present there is a statistically significant rate of
      medial sheath lesions, a previously unpublished association. CONCLUSIONS: With a
      43% association of the medial sheath lesion with SLAP lesions, the author
      postulates that forces that affect the biceps anchor may also damage the pulley
      system of the bicipital sheath and, as such, this anatomic structure should be
      evaluated, especially when SLAP lesions are present.

PMID- 19838384
TI  - Clinical and radiological instability following standard fenestration discectomy.
AB  - BACKGROUND: Post-surgical lumbar instability is an established complication but
      there is limited evidence in the literature regarding the incidence of lumbar
      instability following fenestration and discectomy. We analyzed our results
      following fenestration discectomy with a special focus on instability. MATERIALS
      AND METHODS: Eighty-three patients between the age of 17 and 52 years who had
      undergone fenestration discectomy for a single-level lumbar intervertebral disc
      prolapse were followed-up for a period of 1-5 years. The criteria for instability
      included "instability catch,", "painful catch," and "apprehension." The working
      capacity of the patient and the outcome score of the surgery were assessed by
      means of the Oswestry disability score and the Prolo economic and functional
      outcome score. Flexion-extension lateral radiographs were taken and analyzed for
      abnormal tilt and translation. RESULTS: Of the 83 patients included, 70 were men
      and 13 were women, with an average age of 37.35 years (17-52 years) at 5 years
      follow-up. Clinical instability was seen in 10 (12.04%) patients. Radiological
      instability was noted in 29 (34.9%) patients. Only six (60%) of the 10 patients
      who demonstrated clinical instability had radiological evidence of instability.
      Twenty (68.96%) patients with radiological instability were asymptomatic. Three
      (10.34%) patients with only radiological instability had unsatisfactory outcome.
      The Oswestry scoring showed an average score of 19.8%. Mild disability was noted
      in 59 (71.08%) patients and moderate disability was seen in 24 (28.91%) patients.
      None of the patients had severe disability. These outcomes were compared with the
      outcomes in other studies in the literature for microdiscectomy and the results
      were found to be comparable. CONCLUSION: The favorable outcome of this study is
      in good agreement with other studies on microdiscectomy. Clinical instability in
      12.04% of the patients is in agreement with other studies. Radiological signs of
      instability are seen even in asymptomatic patients and so are not as reliable as
      clinical signs of instability. Standard fenestration discectomy does not
      destabilize the spine more than microdiscectomy.

PMID- 19838385
TI  - Odontoid fractures: A retrospective analysis of 53 cases.
AB  - BACKGROUND: The management of odontoid fracture has evolved but controversy
      persists as to the best method for Type II odontoid fractures with or without
      atlantoaxial (AA) instability. The anterior odontoid screw fixation can be
      associated with significant morbidity while delayed odontoid screw fixation has
      shown to be associated with reasonable good fusion rates. We conducted a
      retrospective analysis to evaluate the outcome of a trial of conservative
      management in type II odontoid fractures without atlantoaxial instability (Group
      A) followed by delayed odontoid screw fixation in cases in which fusion was not
      achieved by conservative treatment. The outcome of type II odontoid fracture with
      AA subluxation (Group B) was also analysed where closed reduction on traction
      could be achieved and in those atlantoaxial subluxations that were irreducible an
      intraoperative reduction was done. MATERIALS AND METHODS: A retrospective
      evaluation of 53 cases of odontoid fractures treated over a 9-year period is
      being reported. All odontoid fractures without AA instability (n=29) were
      initially managed conservatively. Three patients who did not achieve union with
      conservative management were treated with delayed anterior screw fixation. Twenty
      four cases of odontoid fractures were associated with AA instability; 17 of them
      could be reduced with skeletal traction and were managed with posterior fusion
      and fixation. Of the seven cases that were irreducible, the initial three cases
      were treated by odontoid excision followed by posterior fusion and fixation;
      however, in the later four cases, intra operative reduction was achieved by a
      manipulation procedure, and posterior fusion and fixation was performed. RESULTS:
      Twenty-six of 29 cases of odontoid fracture without AA instability achieved
      fracture union with conservative management whereas the remaining three patients
      achieved union following delayed anterior odontoid screw fixation. 17 out of 24
      odontoid fracture with atlantoaxial dislocation could be reduced on traction and
      these patients underwent posterior fusion and fixation. Optimal or near optimal
      reduction was achieved by on table manipulation in four cases which were
      irreducible with skeletal traction. Atlantoaxial stability was achieved in all
      cases. All cases were noted to be stable on evaluation with x-rays at six months.
      CONCLUSIONS: The initial conservative management and use of odontoid screw
      fixation only in cases where conservative management for 6-12 weeks has failed to
      provide fracture union have shown good outcome in type II odontoid fracture
      without AA instability rates. Intraoperative manipulation and reduction in
      patients where AA subluxation failed to reduce on skeletal traction followed by
      posterior fusion obviates the need for transoral odontoid excision.

PMID- 19838386
TI  - Unicompartmental knee arthroplasty for tricompartment osteoarthritis in
      octogenarians.
AB  - BACKGROUND: Unicompartmental knee arthroplasty (UKA) is specifically indicated in
      isolated unicompartmental arthritis with competent ligaments. Recent series of
      UKA for unicompartmental arthritis have shown good function, persistence of pain
      relief, and nearly 90% survivorship at 15 years, even in knees that would perhaps
      not be considered good indications for UKA today. The perioperative morbidity of
      UKA is less than total knee arthroplasty. We present our series of 19
      octogenarians with tricompartment osteoarthritis (predominant medial compartment
      involvement) treated with UKA as definitive surgery. MATERIALS AND METHODS: We
      performed UKA on 29 knees (19 patients) average 83 years (79-94 years) of either
      sex from Jan 2002 to Dec 2006. All the patients had tricompartment knee
      osteoarthritis (with predominant medial and some patellofemoral compartment
      involvement). RESULTS: The results were evaluated using the Knee Society scores
      and visual analogue score over an average 48-month follow-up (range, 24 to 81
      months). Barring one (medial femoral condyle fracture detected on postoperative
      radiography), all patients achieved promised levels of satisfaction. DISCUSSION:
      UKA for tricompartment knee arthritis in the young active patient entails risk of
      dissatisfaction and failure. We present UKA in select 'very elderly' patients
      with tricompartment osteoarthritis (with predominant unicompartment involvement).

PMID- 19838388
TI  - Evaluation of the clinical signs of anterior cruciate ligament and meniscal
      injuries.
AB  - BACKGROUND: The diagnostic accuracy of anterior drawer (AD) sign, Lachman test
      and the pivot shift test for anterior cruciate ligament injury and McMurray test
      for medial and lateral meniscus is varied with sensitivity and specificity
      ranging from 2 to 100%. Generally, it is accepted that the pivot shift test is
      the most specific test to diagnose anterior cruciate ligament (ACL) tears and
      that the Lachman test is more sensitive than AD sign. This study was undertaken
      to calculate the sensitivity, specificity, positive predictive value, negative
      predictive value, and efficiency for the above-mentioned diagnostic tests.
      MATERIALS AND METHODS: Twenty-eight male patients with clinical ACL injury were
      examined in the outpatient department and under anaesthesia, the findings were
      compared with arthroscopy. RESULT: The sensitivity and specificity for the
      Lachman test, AD sign and pivot shift test performed in the outpatient setting
      are 78.6 and 100%, 89.3 and 100%, and 75 and 100%, respectively. The sensitivity
      and specificity for the Lachman test, AD sign, and pivot shift test performed
      under anesthesia are 92.9 and 100%, 92.9 and 100%, and 100 and 100%,
      respectively. The sensitivity and specificity of the McMurray test for medial and
      lateral meniscus were 35.7 and 85.7% and 22.2 and 100%, respectively. CONCLUSION:
      The Lachman test, AD sign and pivot shift test are highly specific tests to
      diagnose ACL laxity in a non-acute setting; pivot shift test under anesthesia is
      the most sensitive and specific test for diagnosing ACL laxity in a non-acute
      setting and the McMurray test is not a sensitive test to diagnose meniscal injury
      in the presence of ACL injury.

PMID- 19838387
TI  - The INDUS knee prosthesis - Prospective multicentric trial of a posteriorly
      stabilized high-flex design: 2 years follow-up.
AB  - BACKGROUND: The anatomical and morphological differences and high-flexion daily
      activities in the Asian population have since ever prompted for development of
      customized knee replacement systems. INDUS knee system has advantages both of
      high-flex designs and is developed by keeping the anatomical variations of the
      native population in mind. The purpose of this study is to analyze the 2-year
      follow-up results using the INDUS prosthesis. MATERIALS AND METHODS: Two hundred
      and ninety-seven knees in 276 patients were prospectively analyzed. There were 65
      men (72 knees) and 211 (225 knees) women with a mean age of 64.56 years. Two
      hundred and forty-five knees had primary osteoarthritis, 48 knees had rheumatoid
      arthritis, and four knees had post-traumatic arthritis. Clinical parameters,
      including the Knee Society scores (knee score and function score), range of
      motion, post-operative anterior knee pain, and complications were recorded. Pre-
      and post-operative serial radiographs were analyzed for limb alignment, component
      positioning, and evidence of loosening. RESULTS: The patients were followed-up
      for an average of 2.59 years (range, 2-3.3 years). The mean knee score and the
      mean function score were significantly improved from a pre-operative value of
      39.4 points and 46.7 points to a post-operative value of 87 points and 86 points,
      respectively (P value <0.05). Two hundred and thirty four knees had no anterior
      knee pain while 63 knees had mild to moderate pain, but none of the patients
      requested any intervention for the same. Of the 276 patients (297 knees), 79
      knees had flexion above 140 degrees , 167 had a flexion range of 130-140 degrees
      , 27 had a flexion range of 100-130 degrees , and 24 knees had a flexion < 100
      degrees , with the mean range of movement being 132.9 degrees . Improvements in
      the range of movement were retained over time and a total of 205 patients (224
      knees, 75.7%) could squat or sit cross-legged at the final follow-up. The mean
      tibiofemoral angle was 8.5 degrees +/-6.9 degrees of varus pre-operatively and
      5.4 degrees +/-2.2 degrees of valgus (3-7 degrees of valgus) at the final follow
      up, with no loss of alignment noted in any case. One knee underwent revision for
      late infection while another knee had periprosthetic supracondylar fracture
      treated with plate fixation. CONCLUSIONS: Use of the INDUS knee prosthesis has a
      favorable short-term outcome, with a mean range of 135 degrees flexion and
      excellent knee scores.

PMID- 19838389
TI  - Metacarpal lengthening by distraction histiogenesis in adults.
AB  - BACKGROUND: Metacarpal lengthening in the hand is a new application for
      distraction neo-histiogenesis. Metacarpal lengthening with distraction helps in
      improvement in pinch function. Thumb lengthening is technically easy in
      comparison to other metacarpals. We present the operative treatment and post
      operative outcome in nine patients with amputations and congenital anomalies.
      MATERIALS AND METHODS: Nine patients underwent distraction osteogenesis for the
      treatment of amputations of the hand and other congenital anomalies. The dominant
      right hand was operated in eight cases and the left hand in one case. There were
      six males and three females. Improvement of function was always the aim of
      surgery. Age range was between 18 and 23 years. Thumb lengthening was performed
      in five patients and that of the index finger in four patients. Distraction
      started on the fifth post-operative day at the rate of 0.25 mm/day. Sensory
      function and bone consolidation was assessed before fixator removal. RESULTS: The
      mean duration of distraction was 51 days (range, 42-60 days) and the distractor
      was removed at a mean of 150 days (range, 140 and 160 days) and the bones were
      lengthened by a mean of 24 mm (range, 20-28 mm) There was improvement of function
      in all cases. CONCLUSION: The metacarpal lengthening by distraction histiogenesis
      in congenital and traumatic amputations is safe and simple method to improve
      pinch function of hand.

PMID- 19838390
TI  - Hip arthrodesis in children: A review of 28 patients.
AB  - BACKGROUND: The best method of treating intractable hip pain in an unsalvageable
      hip joint in a child is still a subject open to debate. We believe that hip
      arthrodesis in such patients provides a painless and stable hip for most
      activities of daily living in our challenging rural terrain. Therefore, we
      conducted this study to assess the functional ability of children with painful
      hip arthrosis treated by arthrodesis of the hip. MATERIALS AND METHODS: A
      retrospective evaluation of 28 children (out of 35) who had an arthrodesis of the
      hip performed between 1994 and 2008 was carried out. The average age was 14
      years, with 12 males and 16 females. There was involvement of the right hip in 13
      and left in 15 cases. The average duration of follow-up was 4.87 years. The
      preferred position of the hip for arthrodesis was 20-30 degrees of flexion,
      neutral abduction-adduction, and neutral rotation, irrespective of the method of
      fixation. RESULTS: The average duration of clinical and radiological arthrodesis
      was found to be 4 months (2-6 months). At the last follow-up, all patients were
      painfree and had good ambulatory capacity. The average Modified Harris Hip Score
      increased from 53 to 84 and the average post-surgical limb length discrepancy was
      1.3 cm, which was well tolerated in all cases. Patients, however, had difficulty
      in squatting and had to modify their posture for foot care, putting on shoes,
      etc. Also, some patients complained of ipsilateral knee, contralateral hip, or
      low back pain with prolonged activity, but this was not severe enough to restrict
      activity except in one case that was known to have juvenile rheumatoid arthritis
      and needed ambulatory aid. CONCLUSION: In an environment where pathology
      generally presents very late and often in a dramatic manner, where the patient's
      socioeconomic status, understanding, compliance, and the logistics of follow-up
      are consistently a challenge in management, hip arthrodesis has been an important
      procedure for our patient group, with good short-term results and promising
      midterm, and, hopefully, long-term prospects. In our series of patients, we have
      been successful in restoring painfree mobility.

PMID- 19838391
TI  - Missed Monteggia fracture in children: Is annular ligament reconstruction always
      required?
AB  - BACKGROUND: Chronic (neglected) radiocapitellar joint dislocation is one of the
      feared complications of Monteggia fractures especially when associated with
      subtle fracture of the ulna bone. Many treatment strategies have been described
      to manage chronic Monteggia fracture and the need for annular ligament
      reconstruction is not always clear. The purpose of this study is to highlight the
      management of missed Monteggia fracture with particular emphasis on utility of
      annular ligament reconstruction by comparing the two groups of patients.
      MATERIALS AND METHODS: In a prospective study 12 patients with mean age of 7.4
      years, who presented with neglected Monteggia fractures, were studied. All
      children underwent open reduction of the radiocapitellar joint. Five children
      (Group A) were treated with angulation-distraction osteotomy of ulna and annular
      ligament reconstruction and six cases (Group B) required only angulation
      distraction osteotomy of ulna without ligament reconstruction. In one case an
      open reduction of the radiocapitellar joint was sufficient to reduce the radial
      head and this was included in Group B. The gap between injury and presentation
      was from 3 months to 18 months (mean 9 months). Ten patients were classified as
      Bado I, and one each as Bado II and III respectively. We used the Kim's criteria
      to score our results. RESULT: The mean follow-up period was 22 months. All ulna
      osteotomies healed uneventfully. The mean loss of pronation was 15 degree in
      Group A and 10 degree in Group B. Elbow flexion improved from the preoperative
      range and no child complained of pain, deformity and restriction of activity. The
      elbow score was excellent in 10 cases, and good in two cases. CONCLUSION:
      Distraction-angulation osteotomy of the ulna suffices in most cases of missed
      monteggia fracture and the need for annular ligament reconstruction is based on
      intraoperative findings of radial head instability.

PMID- 19838392
TI  - Use of antibiotic cement-impregnated intramedullary nail in treatment of infected
      non-union of long bones.
AB  - BACKGROUND: In cases with infected non-union, the primary step is eradication of
      the infection before attempting to achieve union. Release of antibiotics from the
      bone cement at a high concentration and its penetration to the surrounding
      tissues, including cortical and cancellous bone, prompted the use of antibiotic
      cement in the control of bone infection. The aim of this study is to summarize
      our experience with the use of antibiotic cement-impregnated intramedullary nail
      (ACIIN) for control of infection in cases of infected non-union with bone defect.
      MATERIALS AND METHODS: We prospectively studied 25 cases of infected non-union
      (23 femora and two tibiae). There were 24 males and one female, with the mean age
      being 33 years (range, 21-58 years). All patients had high-velocity road traffic
      accidents except one patient who had farmland injury. There were seven closed
      fractures, one grade I compound, two grade II compound fractures, five grade IIIA
      compound fractures, and 10 grade IIIB compound fractures. ACIIN was used in all
      cases after adequate debridement. Patients were classified according to the
      amount of bone defect present after debridement: group 1 with bone defect <4 cm
      (n=13), group 2 with bone defect >/=4-<6 cm (n=7), and group 3 with bone defect
      >/=6 cm (n=5). Infection control was judged on the basis of discharge through the
      wound and laboratory parameters. All patients were followed-up, with an average
      follow-up time of 29 months (range, 18-40 months). The mean duration of retention
      of the intramedullary rod was 8 weeks (range, 6-12 weeks). RESULTS: In group 1,
      all cases achieved infection control, with three patients achieving bone union
      without any need of secondary procedure. In group 2, all cases achieved infection
      control but the time taken was significantly longer than for group 1 (P value
      0.0002). All the cases required a secondary procedure in the form of either
      interlocking intramedullary nailing with iliac crest bone graft or Ilizarov ring
      fixator application to achieve union. None of the cases in group 3 achieved
      infection control. CONCLUSION: ACIINs are useful for infection control in cases
      of infected non-union with bone defect <6 cm. In cases with defect >6 cm, other
      alternatives should be used.

PMID- 19838394
TI  - Nonsecretory multiple myeloma.
AB  - Multiple myeloma is characterized by clonal proliferation of plasma cells usually
      of the B cell type. The skeletal manifestations are usually osteolytic lesions
      whose differential diagnosis includes primary and secondary bone tumor. This
      tumor is characterized by the presence of abnormal paraprotein 8 in blood and
      urine. However, one to five per cent of the cases do not have any protein. Hence
      they are termed nonsecretory. It often poses a diagnostic dilemma when it is
      presented to orthopedic surgeons with no clear features of the disease. Our case
      report exemplifies such a diagnostic dilemma. A high index of suspicion must be
      borne in mind when excluding multiple myeloma as a cause of pain, pathological
      fracture or lytic lesion.

PMID- 19838393
TI  - Limb conservation in extremity soft tissue sarcomas with vascular involvement.
AB  - BACKGROUND: The major neurovascular involvement and large primary tumors are
      indication of amputation. The present study is an attempt to explore the
      feasibility of a limb salvage surgery in extremity sarcoma cases with major
      vessel involvement. Oncological outcomes and surgery-related morbidities are
      compared with those reported in literature. MATERIALS AND METHODS: A
      retrospective review of all limb salvage surgeries done in our department between
      2005 and 2008 was done and four cases of extremity sarcoma of lower limb
      involving femoral vessels analyzed. Interpretation of data from these cases,
      along with review of literature, is done. RESULTS: In all these cases a wide
      monobloc excision was done adhering to oncological principles. This required
      resection of superficial femoral artery alone in two cases, resection of
      superficial femoral artery along with common femoral vein and femoral nerve in
      another, and of common femoral vein alone in yet another. Reconstruction was done
      in all these cases with reversed long saphenous vein graft. Histopathology of
      resected margins was free of tumor in all the four patients. One patient
      developed local recurrence and one developed distant metastsis. Two were disease
      free for one year with good functional limb, one has been disease-free for three
      years and another was disease-free at two years, after which he defaulted further
      follow-up. One patient developed arterial blowout which required ligation of
      common femoral artery which resulted in gangrene of the limb. He underwent
      amputation. CONCLUSION: Major neurovascular involvement in extremity sarcoma is
      not considered a contraindication for limb salvage surgery. Review of literature
      also supports our view. Post-operative wound related complications are more in
      this group of patients. However, long term functional outcome is good. Literature
      suggests a good long term local control after vascular resection and
      reconstruction.

PMID- 19838395
TI  - Spontaneous subdural hematoma of the thoracolumbar region with massive recurrent
      bleed.
AB  - Spinal subdural hematoma is a rare disorder and can be caused by abnormalities of
      coagulation, blood dyscrasias, lumbar puncture, trauma, underlying neoplasm, and
      arteriovenous malformation. We discuss an unusual case of an elderly woman who
      presented with spontaneous spinal subdural hematoma and developed massive
      rebleeding on the third day following initial evacuation of hematoma. This case
      illustrates that a patient with routine normal coagulation profile and adequate
      hemostasis can still harbor platelet dysfunction (in present case due to
      polycythemia) and later on can manifest as rebleeding and neurological
      deterioration.

PMID- 19838396
TI  - Late arthroscopic retrieval of a bullet from hip joint.
AB  - We describe a case of arthroscopic retrieval of a bullet from the hip joint of an
      18-year-old boy, who sustained the injury four months back, accidentally, while
      bird hunting with a country made shotgun. The surgery was performed with the
      standard ordinary instrumentation of knee arthroscopy. The patient became pain
      free the same evening and started partial weight bearing on the next day of
      surgery. At 13 months follow-up, the patient had returned to normal activity
      without any functional limitations.

PMID- 19838397
TI  - Direct bony invasion of malignant melanoma.
AB  - Malignant melanoma is known to spread by local extention, by the lymphatics by
      the blood stream. Direct invasion of the bone from a cutaneous melanoma is
      unknown. Hence, this case is presented in view of its rarity. A 75-year-old
      Caucasian lady presented with a small papillary lesion in the region of a
      recurrent chronic cellulitis on the lower third of the lateral aspect of the
      right leg. Histopathology diagnosed the lesion as locally advanced malignant
      melanoma. Radiological investigations by X-ray and magnetic resonance imaging
      revealed malignant infiltration of the tibia in its mid and lower third with two
      soft tissue metastatic masses adjacent. Histology following amputation confirmed
      malignant melanoma with cranial resection margin involvement. She underwent a
      further above-knee amputation followed by chemotherapy. The patient recovered
      from the amputation but subsequently died 6 months later due to bronchopneumonia
      from lung metastasis.

PMID- 19838398
TI  - Vertebroplasty for osteoporotic vertebral fractures: Additional concern on its
      usefulness.

PMID- 19838399
TI  - Author's reply.

PMID- 19838400
TI  - Elements regulating Potato leafroll virus sgRNA1 translation are  located within 
      the coding sequences of  the coat protein and  read-through domain.
AB  - Translation of viral proteins from subgenomic RNAs (sgRNAs) is a common strategy
      among positive-stranded RNA viruses. Unlike host mRNA, sgRNA of Potato leafroll
      virus (PLRV) does not possess a cap at its 5' end nor a poly(A) tail at the 3'
      terminus, both of which are known to be crucial for translation of RNA in
      eukaryotic cells. Here, we demonstrate, that in wheat germ extract (WGE)
      truncation of the sgRNA1 5' UTR increases translation efficiency, as it has
      previously been observed in rabbit reticulocyte lysate (RRL), whereas removal of
      the 3' UTR does not affect translation. We also describe two regulatory elements
      located within the coding sequence of the coat protein (CP) gene and its read
      through domain (RTD) and are responsible for regulation of in vitro translation
      of the PLRV sgRNA1. The frst element is composed of the purine sequence AAAGGAAA
      located between the AUG codons of the CP and 17K genes. Deletion of this domain
      or its substitution by pyrimidines reduced by half the translation of both genes,
      whereas deletion of the RTD resulted in a 3.6-fold reduction in translation
      efficiency. This is the first report of translation regulatory elements of plant
      viruses located within a coding region.

PMID- 19838403
TI  - Engineered nanoparticle surfaces for improved mass spectrometric analyses.
AB  - Engineering of nanoparticle surface functionality provides controlled
      interactions with biomolecules such as cell membrane lipids, proteins and nucleic
      acids. Concurrently, this surface chemistry control also opens up new avenues for
      improving mass spectral analyses. In this Minireview, we highlight some of the
      emerging work that integrates surface-engineered nanoparticles with mass
      spectrometry to improve the analysis of a wide variety of chemical and biological
      systems.

PMID- 19838404
TI  - Functional electrospray emitters.
AB  - Electrospray ionisation (ESI) is a soft technique used in mass spectrometry (MS)
      analysis able to introduce a wide variety of analytes in the gas phase. Briefly,
      it consists in the application of a high-voltage to a solution to spray it
      through a small orifice. Hence, charged droplets and ions produced in the gas
      phase are directed towards a counter electrode. Based on the electrospray process
      itself, it is possible to carry out diverse experiments by adding functions at
      three different levels. The first one, taking advantage of the microfluidic
      nature, incorporates operation units such as mixers, reactors or chromatographic
      elements into the emitter. In this part, biphasic electrospray ionisation (BESI)
      sources will also be presented. The electrochemical properties of ESI provide the
      second level of functionalities. Electrochemistry, being inherent to the ESI
      process, has proved to be useful for different on-line purposes such as protein
      electrolysis or electrochemical-induced chemical derivatisation. Finally, the
      third level is the aerosol zone where a fine mist of charged droplets is formed.
      In this zone, desorption and extraction reactions can happen for different
      substrates and vapours. Hence, desorption and extractive electrospray ionisation
      (DESI and EESI, respectively) will be presented with an emphasis on the
      advantages brought by these methods. The present review does not intend to focus
      on the electrospray ionisation technique in itself but rather on the introduction
      of functional emitters for ESI-MS. The first part covers basic concepts required
      for developing the other sections. Then, the different options available at the
      three different levels are reviewed in order to highlight the potential of
      functional ESI in the growing field of mass spectrometry.

PMID- 19838405
TI  - Cellular imaging with secondary ion mass spectrometry.
AB  - This article is a concise review of the application of secondary ion mass
      spectrometry (SIMS) to the imaging of biological cells. The paper covers the
      various advantages and disadvantages of different approaches to SIMS analysis
      with respect to the information that can be gained from the interrogation of the
      cells. Current successes, pitfalls and future potential for SIMS in cell imaging
      are discussed. Developments in instrumentation that create a synergy between the
      traditionally separate fields of static and dynamic SIMS with particular benefits
      for cellular imaging by mass spectrometry are also described. Additionally,
      sample preparation and handling, and data manipulation and visualisation in SIMS
      are discussed.

PMID- 19838406
TI  - Measurement of metabolite formation in single living cells of Chlamydomonas
      reinhardtii using synchrotron Fourier-Transform Infrared spectromicroscopy.
AB  - We demonstrate the capability of synchrotron-based Fourier-Transform Infrared
      spectromicroscopy to detect metabolite formation in single, living cells of the
      unicellular algae Chlamydomonas reinhardtii. We show that the high brightness of
      the source provides a sufficient signal-to-noise ratio to detect small molecular
      species accumulating in a spot about 15 microm in size. Time resolved
      measurements are carried out on cells grown heterotrophically under low-light
      conditions to study the evolution of products of anaerobic metabolism. The
      formation of small molecular species, including ethanol and at least one carbonyl
      containing compound, can be detected with a time resolution of the order of one
      minute.

PMID- 19838407
TI  - Near-infrared broad-band cavity enhanced absorption spectroscopy using a
      superluminescent light emitting diode.
AB  - A fibre coupled near-infrared superluminescent light emitting diode that emits
      approximately 10 mW of radiation between 1.62 and 1.7 microm is employed in
      combination with a broad-band cavity enhanced spectrometer consisting of a linear
      optical cavity with mirrors of reflectivity approximately 99.98% and either a
      dispersive near-infrared spectrometer or a Fourier transform interferometer.
      Results are presented on the absorption of 1,3-butadiene, and sensitivities are
      achieved of 6.1 x 10(-8) cm(-1) using the dispersive spectrometer in combination
      with phase-sensitive detection, and 1.5 x 10(-8) cm(-1) using the Fourier
      transform interferometer (expressed as a minimum detectable absorption
      coefficient) over several minutes of acquisition time.

PMID- 19838408
TI  - Self-referencing optrode technology for non-invasive real-time measurement of
      biophysical flux and physiological sensing.
AB  - Vibrating probe technology has enabled scientific investigations that have
      expanded our knowledge of form and function in biology, but the emergence of new
      fields of cytomics and physiomics will require new technologies to probe the
      functional realm of living cells. In this paper, we present the development of a
      self-referencing optrode, which represents the next generation of biophysical
      flux sensors based on phase-sensitive detection for cell and tissue physiology.
      One key advantage is that optical approaches do not suffer from the inherent
      electrical artifacts which limit the performance of traditional vibrating, or
      self-referencing probe technology. In self-referencing modality, the optrode is
      oscillated (0.1 Hz) between two points a few microns apart in a concentration
      gradient, converting the optrodic oxygen concentration sensor into a dynamic flux
      sensor, based on Fick's law. Because of the inherent noise and drift filtering
      associated with phase-sensitive detection it is now possible to measure pico
      molar flux levels using a micro-optrode. In this paper, we show the calibration,
      characterization and application of the self-referencing oxygen optrode for
      measuring biophysical oxygen flux.

PMID- 19838409
TI  - Precision milled flow-cells for chemiluminescence detection.
AB  - Novel flow-cells with integrated confluence points and reaction channels designed
      for efficient mixing of fast chemiluminescence systems were constructed by
      machining opposing sides of a polymer chip and sealing the channels with
      transparent epoxy-acetate films. A hole drilled through the chip provided the
      conduit from the confluence point on one side to the centre of the reaction zone
      on the other side, allowing rapid presentation of the reacting mixture to the
      photodetector. The effectiveness of each flow-cell was evaluated by comparing the
      chemiluminescence intensity using flow injection analysis methodology, and
      examining the distribution of light emanating from the reaction zone (captured by
      photography in a dark room) when the reactants were continuously merged. Although
      previously reported chemiluminescence detectors constructed by machining channels
      into polymers have almost exclusively been prepared using transparent materials,
      we obtained far greater emission intensities using an opaque white chip with a
      thin transparent seal, which minimised the loss of light through surfaces not
      exposed to the photomultiplier tube. Furthermore, this approach enabled the
      exploration of reactor designs that could not be incorporated in traditional
      coiled-tubing flow-cells.

PMID- 19838410
TI  - Identification of rare progenitor cells from human periosteal tissue using
      droplet microfluidics.
AB  - The isolation and characterisation of single cells from a heterogeneous
      population are important processes in cell biology, immunology, stem cell
      research, and cancer research. In the development of novel cell-based therapies,
      there is a considerable need to target specific cell types to allow for further
      analysis and amplification ex vivo. We introduce, herein, the use of droplet
      based microfluidics as a platform technology for the identification and
      quantification of distinct cell phenotypes. Using molecular labelling of specific
      cell populations by antibodies and fluorescent dyes, detection of single cells
      encapsulated within picolitre-sized aqueous droplets can be performed using high
      sensitivity confocal fluorescence detection. Specifically, rare progenitor cells
      were immunodetected within a heterogeneous population of cells isolated from
      human periosteal tissue. Using this model human cell population, the accuracy and
      reproducibility of the droplet system were tested and the results were verified
      using conventional flow cytometry. It was found that the quantitation of
      phenotypic subpopulations measured using both techniques is directly comparable.
      Accordingly, this study demonstrates the biological capacity of droplet-based
      microfluidics for cellular analysis and provides a necessary first step towards
      the development of a novel cell sorting technology.

PMID- 19838411
TI  - Homogeneous temperature- and substrate-resolved technology for a
      chemiluminescence multianalyte immunoassay.
AB  - A novel dual-resolution chemiluminescence (CL) immunoassay platform for the
      homogeneous determination of four proteins is proposed. The immunoassay is based
      on temperature- and substrate-resolved technologies. As a proof-of-concept, we
      evaluated our method for the simultaneous determination of four model proteins
      (i.e. immunoglobulin A (IgA), IgG, IgM and PEGylated recombinant growth hormone
      (GH, protein drug)) by using two homogeneous carriers (thermo-sensitive poly-N
      isopropylacrylamide (PNIP) and magnetic beads (MB)), and two different CL
      substrates for alkaline phosphatase (ALP) and horseradish peroxidase (HRP).
      Briefly, one pair of capture antibodies was immobilized on the PNIP and another
      pair of capture antibodies was bound to the MB. The four carrier-antibody
      conjugates were mixed and reacted with the four proteins in a single vessel, and
      the mixture of two ALP- and two HRP-labeled tracer antibodies was subsequently
      added to form the four sandwich immunocomplexes. After washing, the two MB
      conjugates could be easily separated from the two PNIP conjugates by magnetic
      force while ensuring that the temperature was lower than the lower critical
      solution temperature (LCST). The CL substrates for ALP and HRP were delivered
      sequentially into the resultant MB and PNIP solutions. A simple CL setup was
      employed to perform our novel multiplexed protein assays in the measurement order
      of ALP and HRP. No obvious cross-reaction was observed. IgA, IgG, IgM and GH were
      found to be suitably assayed in the ranges of 1.0-50, 0.50-50, 0.50-50 and 0.50
      50 ng/mL with limits of detection of 0.50, 0.25, 0.25 and 0.25 ng/mL,
      respectively. Overall, this simple and homogeneous technique will find
      applications in areas such as genomics, combinatorial chemistry, drug screening
      and clinical diagnosis.

PMID- 19838413
TI  - Conversion of multiple analyte cation types to a single analyte anion type via
      ion/ion charge inversion.
AB  - Charge inversion ion/ion reactions can convert several cation types associated
      with a single analyte molecule to a single anion type for subsequent mass
      analysis. Specifically, analyte ions present with one of a variety of cationizing
      agents, such as an excess proton, excess sodium ion, or excess potassium ion, can
      all be converted to the deprotonated molecule, provided that a stable anion can
      be generated for the analyte. Multiply deprotonated species that are capable of
      exchanging a proton for a metal ion serve as the reagent anions for the reaction.
      This process is demonstrated here for warfarin and for a glutathione conjugate.
      Examples for several other glutathione conjugates are provided as supplementary
      material to demonstrate the generality of the reaction. In the case of
      glutathione conjugates, multiple metal ions can be associated with the singly
      charged analyte due to the presence of two carboxylate groups. The charge
      inversion reaction involves the removal of the excess cationizing agent, as well
      as any metal ions associated with anionic groups to yield a singly deprotonated
      analyte molecule. The ability to convert multiple cation types to a single anion
      type is analytically desirable in cases in which the analyte signal is
      distributed among several cation types, as is common in the electrospray
      ionization of solutions with relatively high salt contents. For analyte species
      that undergo efficient charge inversion, such as glutathione conjugates, there is
      the additional potential advantage for significantly improved signal-to-noise
      ratios when species that give rise to 'chemical noise' in the positive ion
      spectrum do not undergo efficient charge inversion.

PMID- 19838412
TI  - Signature peptides of influenza nucleoprotein for the typing and subtyping of the
      virus by high resolution mass spectrometry.
AB  - The use of high resolution mass spectrometry to record the accurate mass of
      signature peptides within proteolytic digests of the nucleoprotein antigen, and
      whole influenza virus, is shown to be able to rapidly type and subtype the virus.
      Conserved sequences for predicted tryptic peptides were identified through
      alignments of those for the nucleoprotein across all influenza types and
      subtypes. Peptides with unique theoretical masses from those generated in silico
      for all influenza antigen sequences, and from those proteins known to contaminate
      virus preparations in laboratory grown samples, were identified using a purpose
      built algorithm (FluGest). The frequency of occurrence of such conserved peptide
      signatures was assessed across all nucleoprotein sequences to subsequently type
      and subtype human strains of the virus. The application of the approach is
      illustrated for both type A H1N1 and H3N2, and type B strains of human influenza
      virus.

PMID- 19838415
TI  - Covalently modified graphitic carbon-based stationary phases for anion
      chromatography.
AB  - Carbon-clad zirconia particles have been converted into ion-exchange media by in
      situ diazonium generation and thermal deposition. The surfaces prepared possess
      either a permanently charged anion-exchange site or a weak anion-exchange site.
      Surface modification optimization experiments were performed both on planar
      carbon surfaces and on non-porous 2 microm and porous 3 microm carbon-based
      particles. Modification by traditional electrochemical and thermal deposition
      were compared. Surface modification with the tertiary amine functionality, N,N
      dimethyl-p-phenylenediamine, yielded a capacity of 6.5 microequiv./column, stable
      retention for >33,000 column volumes and retention reproducibility of <2% RSD. A
      quaternary amine functionality (strong base exchanger) was achieved by reaction
      of the tertiary amine phase with methyl iodide. Utilizing short columns (35 x 4
      mm i.d.) mixtures of common inorganic anions were separated with efficiencies of
      21,000 plates/m.

PMID- 19838414
TI  - Direct quantitative determination of adsorbed cellulase on lignocellulosic
      biomass with its application to study cellulase desorption for potential
      recycling.
AB  - Effective hydrolysis of pretreated lignocellulose mediated by cellulase requires
      an in-depth understanding of cellulase adsorption and desorption. Here we
      developed a simple method for determining the adsorbed cellulase on cellulosic
      materials or pretreated lignocellulose, which involves (i) hydrolysis of adsorbed
      cellulase in the presence of 10 M of NaOH at 121 degrees C for 20 min, and (ii)
      the ninhydrin assay for the amino acids released from the hydrolyzed cellulase.
      The major lignocellulosic components (i.e., cellulose, hemicellulose, and lignin)
      did not interfere with the ninhydrin assay. A number of cellulase desorption
      methods were investigated: pH change as well as the use of detergents, high salt
      solution, and polyhydric alcohols. The pH adjustment to 13.0 and the elution by
      72% ethylene glycol at neutral pH were among the most efficient approaches for
      desorbing the adsorbed cellulase. For the recycling of active cellulase, a modest
      pH adjustment to 10.0 may be a low-cost viable method to desorb active cellulase.
      It was found that more than 90% of cellulase for hydrolysis of the pretreated
      corn stover could be recycled by washing at pH 10.0.

PMID- 19838416
TI  - Characterizing the precision of mass-spectrometry-based metabolic profiling
      platforms.
AB  - In conventional analytical chemistry it is customary to report figures of merit -
      such as precision, analysis time, limit of detection - for the chemical analysis
      performed. Usually, such figures of merit are reported for each analyte
      separately, generating a list of figures of merit. In metabolomics such a listing
      is not informative, since very many compounds are measured. An ANOVA-based
      strategy is proposed for a global measure of precision of the whole experiment,
      broken down in components of variation contributing to the total variation. This
      strategy uses well established statistical techniques and can be used easily. It
      was implemented to study the reproducibility of different comprehensive GC- and
      LC-MS methods for the analysis of tobacco aerosols. The results give insight into
      different sources of variation contributing to the total variation, such as
      biological variability, sampling variability and repeatability. For the specific
      example, median CV values ranged from 4.6% to 12.5% for repeatability; from 14.7%
      to 18.0% for sampling variability and, finally, from 24.2% to 26.8% for
      biological variability. Such a breakdown of sources of variability gives clues
      for improving the methods.

PMID- 19838417
TI  - The environmental effect on the fluorescence intensity in solution. An analytical
      model.
AB  - In this paper a mathematical model describing the non-specific interactions of
      the medium surrounding a fluorophore on its fluorescence intensity is proposed.
      The model, which has been developed for quantitative analytical applications, is
      based on the following general ideas: (1) the medium affects the fluorescence
      quantum yield across the non-radiative decay constant (k(nr)); (2) the k(nr) can
      be simplified to the singlet-to-triplet intersystem crossing (k(ISC)) constants;
      (3) k(ISC) follows the energy gap law and then depends on the singlet and triplet
      energy difference, and (4) the medium, due to solvation, changes the energy of
      both excited levels (singlet and triplet), then the constants and finally the
      fluorescence intensity. In our model, the strength of the fluorophore solvation
      by the solvent (represented by its refraction index, n, dielectric constant,
      epsilon, and electric charge) changes the singlet (excited)-to-fundamental and
      the singlet-to-triplet energy gaps, thus the k(ISC) and k(IC) (internal
      conversion constant) values and in consequence the fluorescence quantum yield.
      The final model relates the fluorescence intensity (F) with the solvent
      dielectric constant and refraction index. Finally, the model is particularized
      for the case of a medium composed of a solvent and a solute, obtaining an F-to
      solute concentration relationship and enabling this fact to be used for
      analytical applications. The very first experimental data are shown demonstrating
      the fulfilment of this model.

PMID- 19838418
TI  - Amperometric assessment of functional changes in nanoparticle-exposed immune
      cells: varying Au nanoparticle exposure time and concentration.
AB  - A mast cell/fibroblast co-culture system is used as a model to assess the
      toxicity of Au nanoparticles over the course of 72 hours of exposure. Cellular
      uptake of nanoparticles was found to increase over the 72 hr exposure period and
      the nanoparticles localized within granular bodies of the primary culture mast
      cells. These granules were found to increase in volume with the addition of
      nanoparticles. There was no decrease in viability for 24 hr exposed cells but a
      slight viability decrease was found after 48 and 72 hr exposure. Carbon-fiber
      amperometry analysis of exocytosis of serotonin from mast cells revealed changing
      release profiles over the time course of exposure. In early exposure times,
      granular secretion of serotonin increased with exposure to Au nanoparticles
      whereas 72 hr exposure showed decreased secretion of serotonin with nanoparticle
      exposure. The kinetics of this release was also found to be affected by Au
      colloid exposure where the rate of serotonin expulsion decreased with increasing
      nanoparticle exposure. These results illustrate the dynamic nature of
      nanoparticle-cell interactions and the critical changes in cell behavior even
      when viability is unaffected.

PMID- 19838419
TI  - Why 'the bigger the better' is not always the case when utilising microelectrode
      arrays: high density vs. low density arrays for the electroanalytical sensing of
      chromium(VI).
AB  - We demonstrate, with the example of the electroanalytical sensing of chromium(vi)
      using ultra-microelectrode arrays, that a larger number of microelectrodes
      comprising an array do not necessarily provide improved electroanalytical
      performance. Using a low density array, which consists of 256 microdiscs where
      each microdisc comprising the array has a radius of 10 microns in a cubic
      arrangement separated from their nearest neighbour by 100 microns, the
      electroanalytical sensing of chromium(vi) is shown to be possible over the range
      13-428 microM with a limit of detection of 3.4 microM readily achievable. Using a
      high density microelectrode, consisting of 2597 microdiscs where each microdisc
      has a radius of 2.5 microns in a hexagonal pattern which are separated from their
      nearest neighbour by 55 microns, the electroanalytical performance, in terms of
      linear range and sensitivity, is considerably lower going against the
      misconception that a high density array should produce a superior analytical
      response. The reason for this disparity is discussed and it is shown that the
      arrangement of the microelectrodes on the array is critical due to the
      interaction of diffusion zones between neighbouring electrodes allowing analysts
      to make informed decisions on the conscientious choice of microelectrode arrays.

PMID- 19838420
TI  - Application of a nanoporous gold electrode for the sensitive detection of copper
      via mercury-free anodic stripping voltammetry.
AB  - This paper describes how a new mercury-free alternative electrode material,
      nanoporous gold (NPG), was applied to improve the performance of detecting trace
      metals in stripping voltammetry. The NPG electrode was obtained by dealloying Zn
      from Au(x)Zn(1-x) in a 40-60 mol% zinc chloride-1-ethyl-3-methylimidazolium
      chloride (ZnCl(2)-EMIC) ionic liquid. To prevent electrode fouling from
      surfactant adsorption, the short carbon-chain organothiol (3
      mercaptopropyl)sulfonate (MPS) was selected to modify the NPG electrode through
      the formation of a self-assembled monolayer (SAM). The MPS-modified NPG (MPS@NPG)
      electrode not only significantly enhanced the sensitivity in detecting Cu(2+) but
      also effectively prevented electrode surface fouling from surfactant adsorption.
      The electrode is easy to prepare and can be readily renewed after each stripping
      experiment. The dynamic range of calibration curve, y = 58.76x (in microA microM(
      1)) + 3.90 (R(2) = 0.999), showed very linear behavior with slope of 58.76 microA
      microM(-1) (0.1-5 microg L(-1)). The detection limit is as low as 0.002 microg L(
      1) (0.031 nM). Non-ionic, anionic, and cationic surfactants were found to have no
      effect on Cu(2+) detection when using the MPS@NPG electrode as a sensing probe.
      This method was applied to determining the Cu(2+) in a reference material and
      three real water samples. The results agreed satisfactorily with the certified
      values.

PMID- 19838421
TI  - A highly Li(+)-selective glass optode based on fluorescence ratiometry.
AB  - This paper presents the preparation and characterization of a single-excitation,
      dual-emission ratiometric optical Li(+)-sensing device using a newly designed and
      synthesized highly Li(+)-selective fluoroionophore (KBL-01) carrying 14-crown-4
      ether with tetramethyl and benzene blocking subunits as Li(+)-binding site and
      boron-dipyrromethene as fluorophore. The indicator dye was covalently immobilized
      on the surface of a porous glass support having a large internal surface area
      using a silane-coupling agent. The resulting Li(+)-selective glass optode shows
      dual fluorescence emission response in pseudo-serum at varying Li(+)
      concentrations, allowing ratiometric signal processing. The obtained signal is
      independent of the presence of possibly interfering cations (Na(+), K(+), Mg(2+)
      and Ca(2+)) and pH. The sensor response was found to be reversible within the
      Li(+) concentration range from 10(-4) to 10(-1) M, and showed good repeatability
      and light stability. The plots of the ratiometric signal versus the Li(+)
      concentrations in spiked real human serum go along with the response curve in
      pseudo-serum. These results indicate that the novel Li(+)-selective glass optode
      can be employed as a Li(+)-sensing device with high durability, sensitivity and
      accuracy for medical analyses.

PMID- 19838422
TI  - Biosensor for luteolin based on silver or gold nanoparticles in ionic liquid and
      laccase immobilized in chitosan modified with cyanuric chloride.
AB  - Novel and effective biosensors based on Ag or Au nanoparticles dispersed in ionic
      liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate (BMI.PF(6)) and
      laccase (Lac) from Aspergillus oryzae immobilized in chitosan (Chi) chemically
      cross-linked with cyanuric chloride (CC) were constructed. This enzyme catalyzes
      the oxidation of luteolin to the corresponding o-quinone, which is
      electrochemically reduced back to luteolin at 0.35 V vs. Ag/AgCl. Square-wave
      voltammetry was used for the electrochemical determination of luteolin at the Lac
      nanoparticles-BMI.PF(6) biosensors. The best performance was obtained with
      50:20:15:15% (w/w/w/w) as the graphite powder:Chi-CC:Nujol:Ag-BMI.PF(6) or Au
      BMI.PF(6) composition (Lac 0.29 units mL(-1)) in 0.1 M acetate buffer solution
      (pH 4.0) with frequency, pulse amplitude and scan increment at 50 Hz, 100 mV, and
      5.0 mV, respectively. Under optimized conditions, the cathodic currents increased
      linearly for the luteolin concentration range of 0.099-5.825 microM with
      detection limits of 0.054 +/- 0.004 microM (Ag-BMI.PF(6)) and 0.028 +/- 0.002
      microM (Au-BMI.PF(6)). These biosensors demonstrated high sensitivity, good
      repeatability and reproducibility, and long-term stability (13% decrease in
      response over 70 days). The recovery study for luteolin in chamomile tea samples
      gave values of 91.8-104.8%. The influence of Lac immobilized in Chi-CC and
      nanoparticles-BMI.PF(6) contributes to the excellent performance of the
      biosensors.

PMID- 19838423
TI  - Improved quantitative analysis of ion mobility spectrometry by chemometric
      multivariate calibration.
AB  - Traditional peak-area calibration and the multivariate calibration methods of
      principal component regression (PCR) and partial least squares (PLS), including
      unfolded PLS (U-PLS) and multi-way PLS (N-PLS), were evaluated for the
      quantification of 2,4,6-trinitrotoluene (TNT) and cyclo-1,3,5-trimethylene-2,4,6
      trinitramine (RDX) in Composition B explosive mixtures analyzed by temperature
      step desorption ion mobility spectrometry (TSD-IMS). TSD is a technique used to
      partially resolve mixture components before ion mobility analysis by exploiting
      differences in thermal desorption profiles. While TSD was used here, the results
      and conclusions presented are universally applicable to IMS. Although IMS is used
      extensively for trace explosive detection, it has not been sufficiently
      demonstrated in the past for the detailed analysis of specific compositions of
      explosive mixtures. This manuscript combines IMS with multivariate chemometric
      data methods to enhance the quantitative performance of IMS needed for detailed
      explosive analyses. This is demonstrated using data from the replicate TSD-IMS
      analyses of eight different Composition B samples. The true TNT and RDX
      concentrations were determined by analyzing the Composition B samples by high
      performance liquid chromatography with UV absorbance detection. Most of the
      Composition B samples were found to have distinct TNT and RDX concentrations. The
      data from each TSD-IMS analysis were a 2-D array that was reduced by averaging
      into a vector or mean IMS spectrum. Although the mean IMS peaks for TNT and RDX
      were sufficiently resolved to use peak area to generate linear calibration
      curves, the peak-area variability was too large to differentiate Composition B
      samples based on their predicted RDX and TNT concentrations. Applying PCR and PLS
      on the exact same IMS spectra used for the peak-area study improved quantitative
      accuracy and precision approximately 3-to 5-fold and 2- to 4-fold, respectively.
      This in turn improved the probability of correctly identifying Composition B
      samples based upon the estimated RDX and TNT concentrations from 11% with peak
      area to 44% and 89% with PLS. The success of PLS over peak area is attributed to
      multivariate signal averaging and the simultaneous maximization of correlation
      between the entire span of the IMS mean spectra and the known TNT and RDX
      concentrations. In this study, PLS also outperformed PCR and had similar
      quantitative results to U-PLS. In terms of N-PLS, its mean bias values were up to
      2.8 times larger and the mean RSD values were at least 40% larger than those
      obtained by PLS.

PMID- 19838424
TI  - Captavidin: a new regenerable biocomponent for biosensing?
AB  - Functionalisation of a biosensor's sensing surface with the appropriate
      biorecognition elements is essential for the correct performance of the
      biosensor. In this paper, we investigate by Surface Plasmon Resonance (SPR) if
      captavidin, a recently described biotin-binding regenerable protein, could be
      used to bind and release biotinylated biocomponents for the development of
      regenerable biosensors. In our experiments, biotinylated antibodies were
      successfully subjected to up to nine serial capture-release events from the
      captavidin-functionalised surface. Up to three consecutive captures were possible
      when a protein target had been subsequently added. On the other hand,
      biotinylated bacteria were also efficiently captured and released from the gold
      surface, suggesting also the suitability of captavidin for the development of
      whole-cell regenerable biosensors. Our results indicate that captavidin is a
      promising regenerable molecular tool that could be used during biosensor
      optimisation and validation, and that captavidin-modified surfaces could be fine
      tuned into truly reusable sensors.

PMID- 19838425
TI  - An exploratory NMR nutri-metabonomic investigation reveals dimethyl sulfone as a
      dietary biomarker for onion intake.
AB  - The metabolome following intake of onion by-products is evaluated. Thirty-two
      rats were fed a diet containing an onion by-product or one of the two derived
      onion by-product fractions: an ethanol extract and the residue. A 24 hour urine
      sample was analyzed using (1)H NMR spectroscopy in order to investigate the
      effects of onion intake on the rat metabolism. Application of interval extended
      canonical variates analysis (ECVA) proved to be able to distinguish between the
      metabolomic profiles from rats consuming normal feed and rats fed with an onion
      diet. Two dietary biomarkers for onion intake were identified as dimethyl sulfone
      and 3-hydroxyphenylacetic acid. The same two dietary biomarkers were subsequently
      revealed by interval partial least squares regression (PLS) to be perfect
      quantitative markers for onion intake. The best PLS calibration model yielded a
      root mean square error of cross-validation (RMSECV) of 0.97% (w/w) with only 1
      latent variable and a squared correlation coefficient of 0.94. This indicates
      that urine from rats on the by-product diet, the extract diet, and the residue
      diet all contain the same dietary biomarkers and it is concluded that dimethyl
      sulfone and 3-hydroxyphenylacetic acid are dietary biomarkers for onion intake.
      Being able to detect specific dietary biomarkers is highly beneficial in the
      control of nutritionally enhanced functional foods.

PMID- 19838426
TI  - Explanatory multivariate analysis of ToF-SIMS spectra for the discrimination of
      bacterial isolates.
AB  - Multivariate analysis (PC-CVA and GA-CVA) was carried out on time-of-flight
      secondary ion mass spectra (ToF-SIMS) derived from 16 bacterial isolates
      associated with urinary tract infections, with an objective of extracting the
      spectral information relevant to their species-level discrimination. The use of
      spectral pre-processing, such as removal of the dominant peaks prior to analysis
      and analysis of the dominant peaks alone, enabled the identification of 37 peaks
      contributing to the principal components-canonical variates analysis (PC-CVA)
      discrimination of the bacterial isolates in the mass range of m/z 1-1000. These
      included signals at m/z 70, 84, 120, 134, 140, 150, 175 and 200. A univariate
      statistical analysis (Kruskal-Wallis) of the signal intensities at the identified
      m/z enabled an understanding of the discriminatory basis, which can be used in
      the development of robust parsimonious models for predictive purposes. The
      utility of genetic algorithm (GA)-based feature selection in identifying the
      discriminatory variables is also demonstrated. A database search of the
      identified signals enabled the biochemical origins of some these signals to be
      postulated.

PMID- 19838427
TI  - Thyroid tissue analysis through Raman spectroscopy.
AB  - The diagnosis of thyroid pathologies is usually made by cytologic analysis of the
      fine needle aspiration (FNA) material. However, this procedure has a low
      sensitivity at times, presenting a variation of 2-37%. The application of optical
      spectroscopy in the characterization of alterations could result in the
      development of a minimally invasive and non-destructive method for the diagnosis
      of thyroid diseases. Thus, the objective of this work was to study the
      biochemical alterations of tissues and hormones (T3 and T4) of the thyroid gland
      by means of molecular vibrations probed by FT-Raman spectroscopy. Through the
      discriminative linear analysis of the Raman spectra of the tissue, it was
      possible to establish (in percentages) the correct classification index among the
      groups: goitre adjacent tissue, goitre nodular region, follicular adenoma,
      follicular carcinoma and papillary carcinoma. As a result of the comparison
      between the groups goitre adjacent tissue versus goitre nodular region, an index
      of 58.3% of correct classification was obtained; this percentage was considered
      low, and it was not possible to distinguish the Raman spectra of these groups.
      Between goitre (nodular region and adjacent tissue) versus papillary carcinoma,
      the index of correct classification was 64.9%, which was considered good. A
      relevant result was obtained in the analysis of the benign tissues (goitre and
      follicular adenoma) versus malignant tissues (papillary and follicular
      carcinomas), for which the index was 72.5% and considered good. It was also
      possible, by means of visual observation, to find similar vibrational modes in
      the hormones and pathologic tissues. In conclusion, some biochemical alterations,
      represented by the FT-Raman spectra, were identified that could possibly be used
      to classify histologic groups of the thyroid. However, more studies are necessary
      due to the difficulty in setting a standard for pathologic groups.

PMID- 19838429
TI  - Doctors and leadership of healthcare organizations.

PMID- 19838430
TI  - Prophylaxis against infective endocarditis. A review of current international
      guidelines.
AB  - The purpose of this review is to discuss current international guidelines on the
      prevention of infective endocarditis (IE). It has long been considered that all
      patients with heart conditions predisposing to IE should receive antibiotic
      prophylaxis when undergoing procedures leading to bacteremia with organisms known
      to cause endocarditis. However, evidence for this is poor and based on isolated
      case reports, and on theoretical considerations, rather than on randomized
      controlled trials. Recently, thinking has changed for 3 main reasons. Firstly,
      there is now strong evidence that bacteremia with endocarditis-causing organisms
      frequently occurs following everyday activities, such as tooth-brushing.
      Secondly, few cases of endocarditis are directly attributable to a preceding
      procedure. Thirdly, adverse effects of antibiotic use should be given due
      consideration. Recent international guidelines have radically changed
      recommendations on this issue, advocating limited, or non-use of antibiotics in a
      very small group of high-risk individuals for a limited number of invasive
      procedures.

PMID- 19838431
TI  - Effects of trace elements on albumin and lipoprotein glycation in diabetic
      retinopathy.
AB  - OBJECTIVE: To test the effect of some trace elements, on protein and lipoprotein
      glycosylation and their impact on the severity of diabetic retinopathy. METHODS:
      A case control study was conducted in 42 diabetic patients (14 without
      retinopathy [DC]; 14 with non-proliferative diabetic retinopathy [NPDR]; 14 with
      proliferative diabetic retinopathy [PDR]) at Ebin Al-Haitham Specialized
      Hospital, Baghdad, Iraq for Ocular Diseases from February to December 2008. In
      addition to 20 age and gender matched healthy controls (NC). The glycation of
      albumin, alpha-, pre beta-, and beta-lipoproteins was measured by agarose gel
      electrophoresis. Serum levels of cadmium (Cd), selenium (Se), chromium (Cr), zinc
      (Zn), and copper (Cu) were analyzed by flameless atomic absorption
      spectrophotometer. RESULTS: There was significant elevation in the mean serum
      glycated beta-lipoprotein in DC (p<0.05) and a near significant increase (p=0.06)
      in the means of both glycated albumin and pre beta-lipoproteins among the PDR and
      NPDR groups. Moreover, a significant reductions in serum means of Cd (p<0.05) and
      Zn/Cu ratios (p<0.001) were recorded in all diabetic retinopaths as compared to
      DC. The Cd level rises with the increase in duration of diabetes (p<0.001) and
      hyperglycemia (p<0.025) whereas, the serum Cr values decreases with the
      progression of diabetes (p<0.025). CONCLUSION: Both glycation and oxidative
      processes are involved in the development of diabetic retinopathy, and changes in
      the concentration of Cd, Se, Cr, Zn, and Cu have some impact on the disease
      progression.

PMID- 19838432
TI  - Efficacy analysis of methylprednisolone plus adrenaline to treat wasp sting
      injury.
AB  - OBJECTIVE: To observe the effect of methylprednisolone (MP) plus adrenaline to
      treat patients injured by wasp stings. METHODS: This study was carried out at The
      First College of Clinical Medical Science, China Three Gorges University,
      Yichang, Hubei Province, China, from June to November 2008. A total of 45 cases
      were divided into 2 groups. The MP was used alone in the control group, and MP
      plus adrenaline was used in the observation group. We compared the clinical
      effect between the 2 groups. RESULTS: The alanine aminotransferase (ALT) (64.05
      +/- 59.31 versus 124.14 +/- 80.01 U/L), and creatine kinase isoenzyme (CKMB)
      (90.32 +/- 85.19 versus 216.68 +/- 277.58 umol/L) levels of the observation group
      were significantly lower than those of the control group. The length of hospital
      stay of the observation group was significantly shorter than that of the control
      group (7.23 +/- 2.93 versus 11.23 +/- 8.02), while complications from the wasp
      sting were fewer than those of the control group. In addition, the level of
      peripheral blood leukocytes was positively correlated with the number of stings
      (r=0.733, p=0.001), levels of ALT and CKMB (r=0.627, p=0.001, and r=0.705,
      p=0.001), and length of hospital stay (r=0.667, p=0.001). CONCLUSION: Allergic
      and inflammatory responses play an important role in addition to the direct
      effect of wasp venom on the human body. Compared with MP alone, early combination
      of adrenaline helps to further inhibit the diffusion of allergy and inflammatory
      cytokines, and therefore reduce the severity of injury.

PMID- 19838433
TI  - A prospective randomized trial comparing non-stented versus routine stented
      ureteroscopic holmium laser lithotripsy.
AB  - OBJECTIVE: To determine whether post-operative ureteral stenting is necessary
      after ureteroscopic lithotripsy for the treatment of middle and distal ureteral
      calculi. METHODS: The trial was carried out in the Department of Urology of West
      China Hospital, Sichuan University, Chengdu, China, between May 2005 and May
      2006. A total of 110 patients underwent uncomplicated ureteroscopic lithotripsy.
      After the procedure, patients were randomized to a non-stented (n=55), or stented
      (n=55) group. The stent was routinely placed for 3 weeks. Outcome measures
      included operative time, visual analog scale, post-operative analgesic
      requirements, complications, and the stone-free rate. RESULTS: The incidence of
      hematuria was higher and the operative time was longer in the stented group
      compared to the non-stented group. At 48 hours post-operatively, the symptoms of
      flank pain and abdominal pain were significantly greater in the stented group.
      There was no statistical difference in the 2 groups, in terms of irritative
      symptom, analgesic use, and complications. The stone-free rate was almost 100% in
      both groups. CONCLUSION: Uncomplicated ureteroscopic lithotripsy can be safely
      performed without the placement of a ureteral stent. Patients without stents had
      less operative time, pain and hematuria.

PMID- 19838434
TI  - Peri- and post-operative complications after carbon dioxide laser surgery of the
      larynx.
AB  - OBJECTIVE: To analyze the complications of transoral laser surgery (TLS) for
      larynx tumors in a single center institution, and to highlight its possible
      risks. METHODS: This is a retrospective study of the peri- and post-operative
      complications of 500 patients who underwent TLS from November 2001 to July 2008
      in the Department of Otolaryngology, Head and Neck Surgery, Anhui Provincial
      Hospital, Anhui Medical University, Hefei, China. RESULTS: The total rate of
      complications was 10.2%. The major complications accounted for 0.8%, including
      one ignition, one post-operative bleeding, one dyspnea, and one laryngeal web;
      and the minor ones were found in 47 of 500 patients (9.4%), including 30 patients
      with suspension laryngoscopy related complications. A higher incidence of
      complications was observed in patients with larynx carcinoma than those with
      benign/precancerous lesions (p=0.00). CONCLUSION: Peri- and post-operative
      complications after TLS for benign larynx tumors are relatively rare events, but
      are relatively frequent for larynx cancers. Every surgeon who performs laser
      surgery should have a clear concept of management for these complications, and
      strategies to avoid these complications should be performed.

PMID- 19838435
TI  - The Saudi Thrombosis and Familial Thrombophilia Registry. Design, rational, and
      preliminary results.
AB  - OBJECTIVE: To describe the Registry and report preliminary data for the
      prevalence of 5 prothrombotic gene mutations in the normal Saudi population.
      METHODS: Blood from consenting healthy Saudi individuals and patients with venous
      thrombosis (VT) from different regions of the Kingdom was collected from November
      2001 until July 2007. The extracted DNA of each sample was kept at -70 degrees C
      until tested for 5 known prothrombotic factors using established methods. Only
      patients with confirmed VT were included. Data generated through direct interview
      were entered into the Saudi Thrombosis and Familial Thrombophilia (S-TAFT)
      Register. The consent and demographic data collection forms and the S-TAFT
      Register were developed using the SQL web based software. RESULTS: Nine hundred
      and two DNA samples of consenting healthy Saudi individuals were tested for
      factor V Leiden (FVL), prothrombin (PT) 20210 G>A, 5-10 methylenetetrahydrofolate
      reductase (MTHFR) 677 C>T, the 4G/5G polymorphism of Plasminogen activator
      inhibitor type 1 (PAI-1 4G/5G), and factor V HR2 (FVHR2) haplotype. The incidence
      of FVL among healthy subjects was 1.3%, PT 20210 G>A 0.7%, homozygous MTHFR
      677C>T 2.45%, PAI 4G/4G 10.1%, and FVHR2 26.1%. CONCLUSION: Our preliminary data
      from healthy Saudi individuals suggest that the incidence of the 5 prothrombotic
      risk factors is lower than in most other populations, except for FVHR2.

PMID- 19838437
TI  - Perinatal mortality rate in Al-Ramadi Maternity and Children's Hospital, western
      Iraq.
AB  - OBJECTIVE: To estimate the perinatal mortality rate (PMR) in Al-Ramadi city,
      Iraq, and study its associated causative factors following the 2003 Coalition
      Forces occupation of Iraq. METHODS: All the hospital stillbirth, and early
      neonatal death deliveries at the Al-Ramadi Maternity and Children's Hospital, Al
      Anbar Governorate, western Iraq, from 15th June to 15th December 2005 were
      included in the study. Data collected for the mother includes: age, residence,
      parity, plurality, mode of delivery, medical and obstetrical history, antenatal
      care (ANC), and previous perinatal death. For dead babies: gestational age,
      gender, birth weight, and Apgar scores were also collected. RESULTS: The total
      studied deliveries were 3,249 births. The perinatal mortalities were 125 (43
      stillbirths, and 82 neonatal deaths), giving an overall PMR of (38.5/1000). Males
      showed higher PMR (45.9/1000) than females (29.1/1000). Low birth weight babies
      among live births were 939 (29.2%), and were of higher (95.8/1000) PMR than
      normal (15.1/1000) weight births. Significant association was found between the
      gestational age, Apgar score, maternal age, residence, previous medical history,
      previous perinatal death, and plurality with the PMR. While no association was
      found between the mode of delivery, parity, ANC, and PMR. CONCLUSION: This study
      showed lower rates than some Iraqi studies applied before 2003, but still was of
      higher PMR when compared with the rates of most neighboring Arab and other
      developed countries.

PMID- 19838436
TI  - Vitamin D deficiency in Saudi patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine vitamin D status among Saudi patients with systemic lupus
      erythematosus (SLE) versus matched control group. METHODS: Hospital-based cohorts
      of 165 SLE patients and 214 SLE-free volunteers were recruited at King Abdulaziz
      University Hospital in Jeddah, Kingdom of Saudi Arabia between January 2006 and
      June 2008. Serum levels of 25-hydroxyvitamin D [25(OH)D] were measured. Vitamin D
      sufficiency is defined as a serum level of 25(OH)D >75 nmol/L (>30 ng/ml). A
      level ranging between >50 to <75 nmol/L (>20 to <30 ng/ml) is considered as
      vitamin D insufficiency, whereas <50 nmol/L (<20 ng/ml) as vitamin D deficiency.
      Both deficiency and insufficiency are considered to comprise vitamin D
      inadequacy. RESULTS: The prevalence of SLE patients with 25(OH) D inadequacy and
      deficiency was higher than in the control group: 98.8 versus 55%, 89.7 versus 20%
      (p<0.0001). Only 2 (1.2%) SLE patients had adequate levels of 25(OH)D compared to
      96 (45%) of control group (p<0.0001). The mean serum levels (nmol/L) of 25(OH)D
      in SLE patients with vitamin D inadequacy and deficiency in comparison to the
      control group were 22.3 +/- 13.6 versus 44.5 +/- 17.5 (p<0.0001) and 19.1 +/- 9.5
      versus 22.9 +/- 6.7 (p=0.0152). No significant differences were evident in female
      and male patients with SLE with respect to the mean serum levels of 25(OH)D and
      prevalence of its deficiency. CONCLUSION: Vitamin D inadequacy is highly
      prevalent in Saudi patients with SLE. Vitamin D supplementation and its
      evaluation in the treatment of SLE should be considered.

PMID- 19838438
TI  - Maternal risk factors in early neonatal sepsis at a tertiary care teaching
      hospital.
AB  - OBJECTIVE: To study the maternal risk factors in blood culture proven cases of
      early neonatal sepsis, and study the isolates and the sensitivity of these
      isolates. METHODS: This is a case series of all mothers admitted from January
      2008 to December 2008 and registered on a pre-designed Proforma, by the House
      Officers, and Resident Medical Officers of Hamdard College of Medicine &
      Dentistry, Hamdard University Hospital, Karachi, Pakistan. All neonates delivered
      at the hospital were examined; first immediately at birth, and then daily until
      the mother was discharged after 2 to 3 days. Neonates with suspected sepsis were
      included in the study, blood examination, and blood cultures were obtained,
      maternal information such as social status, education, fever at the time of
      labor, use of antibiotics before delivery, onset of labor, and mode of delivery
      were studied in these cultures proven cases of neonatal sepsis. Antibiotics such
      as cefotaxime and amikacin were started on an empirical basis until final
      cultures reports were received. In cases of negative cultures, antibiotics were
      stopped, otherwise, they were continued according to culture and sensitivity for
      10-14 days. RESULTS: The total number of deliveries at Hamdard University
      Hospital from January 2008 to December 2008 was 950. Neonates with suspected
      sepsis comprised 257. Among these 257 cases, 113 neonates had positive blood
      cultures. Staphylococcus aureus being the most common organism in our study
      (59.2%) followed by Klebsiella pneumoniae (19.4%) and Enterococci (19.4%).
      CONCLUSION: This study indicates that the presence of multiple maternal risk
      factors makes a child more susceptible to early onset neonatal sepsis.

PMID- 19838439
TI  - Risk factors for postpartum hemorrhage among Saudi women.
AB  - OBJECTIVE: To identify health-related risk factors for the development of post
      partum hemorrhage (PPH) in Saudi women and to estimate the incidence of primary
      PPH. METHODS: A case-control study was conducted between July 1, 2007 and June
      30, 2008 at King Abdulaziz Medical City, Riyadh, Saudi Arabia. One hundred and
      one patients with PPH and 209 control patients were included. Bivariate
      associations between the different risk factors for the development of PPH were
      studied. Multivariate logistic regression analysis to identify significant risk
      factors for the occurrence of this obstetrics complication was carried out.
      RESULTS: High parity was associated with a 17% increased risk of PPH. Risk
      factors in preeclampsia was associated with >6-fold increase. History of
      antepartum hemorrhage (APH) increased the risk for PPH by >8-fold. Other factors
      were: multiple pregnancy, vaginal delivery, prolonged third stage of labor, and
      presence of cardiotocograph (CTG) abnormalities. CONCLUSION: Risk factors for
      developing PPH among Saudi women are comparable to other reported studies with a
      greater influence of parity, presence of APH, multiple gestation, CTG
      abnormalities and prolonged third stage of labor. There is a need for patient
      education on family planning and antenatal care, physician education on active
      management of the third stage, and correct estimation of blood loss.

PMID- 19838440
TI  - Is routine antenatal screening for syphilis in Nigeria still justified clinically
      and economically?
AB  - OBJECTIVE: To determine the seroprevalence and cost effectiveness of antenatal
      syphilis screening at the University of Maiduguri Teaching Hospital (UMTH),
      Maiduguri, Nigeria. METHODS: A retrospective chart analysis of venereal disease
      research laboratory (VDRL) results among pregnant women at the UMTH, Maiduguri,
      Nigeria, during a 10-year period (from 1st January 1999 to 31st December 2008)
      was undertaken. RESULTS: A total of 18,712 women registered for antenatal care
      during the study period. Of these, 18,101 had serological screening for syphilis.
      Only 12 of the 18,101 screened were seropositive by VDRL, 9 (75%) were confirmed
      by Treponema pallidum hemagglutination assay (TPHA), giving a seroprevalence rate
      of 0.05%. Three (25%) were biological false-positive. The peak age-specific
      incidence of 0.02% was in the 20-24 year-age group. There was zero prevalence in
      the age groups 15-19 and >40 years. There was no case of congenital syphilis
      seen. The cost for VDRL testing per patient in UMTH is US$2. The total amount of
      money spent on VDRL tests over the study period was US$37,424. CONCLUSION: The
      seroprevalence rate of syphilis is extremely low in this study. This calls for a
      review of the policy of routine antenatal serology screening for syphilis in
      Maiduguri, Nigeria.

PMID- 19838441
TI  - Head and neck oncology experience in Makkah, Saudi Arabia.
AB  - OBJECTIVE: To present our experience in head and neck cancer, and the development
      of our own local electronic Makkah Head and Neck Database. METHODS: A prospective
      collection of cases was conducted between October 2007 and November 2008 of
      patients diagnosed with head and neck cancer within the Department of
      Otolaryngology, Head and Neck Surgery at Al-Noor Specialist Hospital, Makkah,
      Kingdom of Saudi Arabia. RESULTS: Forty-four patients were included in this
      study. There were 24 males (54.5%), and 20 females (45.5%). Sixteen patients
      (36.4%) had oral cavity cancer, 10 patients (22.7%) had hypopharyngeal cancer, 10
      patients (22.7%) had nasopharyngeal cancer, 6 patients (13.6%) had thyroid
      cancer, and 2 patients (4.5%) had neck secondary-unknown primary. Thirty-six
      patients (81.8%) presented with stages III and IV versus 8 patients (18.1%) with
      stages I and II (p=0.0016). Twenty-four patients (54.5%) were managed primarily
      by surgery, while 20 patients (45.5%) were managed primarily non-surgically in
      the form of external beam radiotherapy (XRT), or XRT/Chemotherapy. Outcomes were:
      16 patients (38%) were free of any recurrence, 2 patients (5%) died in the
      perioperative period, 2 patients (5%) had loco-regional recurrence, and 24
      patients (54%) were lost follow up. CONCLUSION: All oncological services of head
      and neck cancer patients including surgery, radiotherapy, and chemotherapy should
      be provided in one oncology center, and managed through a standard one channel,
      namely, the Head and Neck Oncology Board, to achieve standard patient care,
      adequate follow up, and surveillance.

PMID- 19838442
TI  - Evaluation of acute postoperative pain monitoring program for nurses in Thailand.
AB  - OBJECTIVE: To evaluate the effectiveness of an acute postoperative pain
      monitoring program (APPMP) on pain knowledge, attitude, and applicability of
      nurses at Prasat Neurological Institute, Bangkok, Thailand. METHODS: This study
      was conducted from 1st March to 31st October 2008, at the Prasat Neurological
      Institute, Bangkok, Thailand. Thirty-five neurological nurses were recruited. The
      effectiveness was evaluated using 3 indicators: pain knowledge score, attitude
      score, and nursing practice score. The mean score from each indicator group was
      calculated as the pre-APPMP launching test based. For the post-APPMP launching
      test, pain knowledge score, and attitude score were measured immediately after
      educating the participants, while the nursing practice score was measured 6
      months later. The descriptive statistics and paired t-test were analyzed.
      Statistical significance was set at p<0.001. RESULTS: The nurses' pain knowledge
      score increased significantly from 36.3-64.8%, together with the practice score
      from 20-32.2% (p<0.001). The nurses' pain attitude scores were 82.4% in the pre
      test, and 84.2% post-test. The patients' satisfaction for the 24 hour post
      operation pain management was 4.2+/-0.73, on a 5-point Likert scale. CONCLUSION:
      The APPMP was effective in improving nurses' pain knowledge and practice.
      Although changing nurses' behavior in controlling patients' pain is possibly time
      consuming, however, education and a consultation system are still necessary.

PMID- 19838443
TI  - Quality of life in people with epilepsy and their family caregivers. An Arab
      experience using the short version of the World Health Organization quality of
      life instrument.
AB  - OBJECTIVE: To assess the subjective quality of life (QOL) of Sudanese epilepsy
      patients with generalized tonic clonic seizures and their family caregivers,
      compared with the general population, and previous Sudanese data for chronic
      conditions, and to examine the predictors of QOL. METHODS: This cross-sectional
      study using the World Health Organization's 26-item QOL instrument, was carried
      out from December 2005 to December 2006, on consecutive government hospital
      Neurology Clinic attendees and their family caregivers, who fulfilled the study's
      inclusion criteria, in the cities of Khartoum, Wad Medani, and Atbara, Sudan.
      RESULTS: There were 276 patients (56.5% male; mean age 29.5 years). Patients' QOL
      scores were significantly lower (physical health domain [57.1%], psychological
      [60.1%], social relations [58.4%], environment [50.6%], and general facet
      [60.8%]), than the control group. They scored lower than the WHO 23-country
      patients for social relations and environment domains, and had lower environment
      domain scores than Sudanese diabetes patients. Caregivers had significantly
      higher scores (57.4 -73.7%) than patients and control group. Patients' higher QOL
      was associated with marriage, education, employment, no side effects and
      caregiver occupation. Caregivers had lower QOL if they were female, patients' own
      children, and less educated. The predictors of QOL included caregiver's proxy
      rating of the patient's QOL and drug side effects. CONCLUSION: Poor QOL in
      epilepsy reflects social underachievement, and calls for programs to remedy their
      psychosocial circumstance, and improve service provisions. Vulnerable caregivers
      need to be identified for assistance, to enhance their role.

PMID- 19838444
TI  - Testing psychiatric stigma in a general hospital in Saudi Arabia.
AB  - OBJECTIVE: To measure the stigma of psychiatric illness in a general hospital
      setting, and to test the connection between common ideas people have of patients
      with psychiatric illness (personal responsibility, and dangerousness), and the
      generation of discriminatory behavior. METHODS: A cross-sectional survey through
      internal mail was carried out in all the hospital staff of King Abdulaziz
      Hospital in Al-Ahsa, Kingdom of Saudi Arabia. The questionnaire was distributed
      on the 1st of February, and the study was finished on the 12th of March 2008. The
      sample size of 860 staff members was included for the study. This study was
      approved by the Eastern Region National Guard's Health Affairs Research and
      Ethical Committee. RESULTS: Hospital staff had high scores (6.8/9) for caring
      attitude for patients with psychiatric illness. They had medium scores for fear
      (4/9), avoidance (4.8/9), and dangerousness (4.3/9). They had low scores (3.1/9)
      for anger feelings toward these patients. Discriminatory behavior was found to be
      the result of feeling that these patients are dangerous, but not because they
      were held responsible for their illness. CONCLUSION: Our staff had a caring
      attitude towards patients with psychiatric illness. The idea that the patients
      with psychiatric illness are to blame for their illness did not hold, while the
      idea that these patients are dangerous showed positive relationship with
      discriminatory behavior.

PMID- 19838445
TI  - The willingness toward deceased organ donation among university students.
      Implications for health education in Saudi Arabia.
AB  - OBJECTIVE: To shed light on the willingness to donate deceased organs and tissues
      among university students in Saudi Arabia. METHODS: This cross-sectional survey
      employed self-administered questionnaires to collect data on demographic
      characteristics, and knowledge-related aspects of students on organ and tissue
      donation. The questionnaires were distributed randomly to 600 students, of which
      487 (81.2%) completed the questionnaire at King Saud University, Riyadh, Saudi
      Arabia, from May to June 2008. The data were analyzed by descriptive statistics,
      chi-square tests, and logistic regression analysis. RESULTS: Most students
      (70.6%) were willing to donate deceased organs and tissues. None of these
      students had a donation card, and 66% of them were ready to sign a donor card.
      The results indicate that those who had information and knowledge on the deceased
      organ donation concept were more willing to donate organs and tissues. Students
      reported that lack of information, personal attitudes, and religious beliefs were
      among the objecting reasons for deceased organ/tissue donation. CONCLUSION: The
      majority of students were willing to donate organs, and more dissemination of
      information can increase the awareness of the public, including students, to the
      importance of organ donation and transplantation in Saudi Arabia.

PMID- 19838446
TI  - Squamous cell carcinoma of the breast.
AB  - Pure primary squamous cell carcinoma of the breast is a rare disease, thus strict
      criteria should be applied when making such a diagnosis. Breast abscesses are a
      common presentation. We report a case of primary SCC of the breast in a 69-year
      old woman in which the initial clinical impression was a breast abscess. She had
      an incision and drainage, and cytological and histological examination revealed
      squamous cell carcinoma. A secondary source was excluded and the patient
      underwent mastectomy, which was followed by a local recurrence in 4 months.

PMID- 19838447
TI  - Pseudomyxoma peritonei. Presenting as a localized perforation of the cecum.
AB  - Pseudomyxoma peritonei (PMP), also known as jelly belly, is a rare condition with
      mucinous material spread throughout the abdomen. It can arise from the appendix,
      colon, or even a teratoma. The documented incidence is one per million per year.
      We present a case report of an 80-year-old female patient presenting with PMP
      secondary to an appendicular tumor leading to localized infiltration, and
      perforation of the cecal wall. A review of the literature was carried out, with
      emphasis on various treatment options available for this rare condition.

PMID- 19838448
TI  - Sudden death of a young ICU doctor by injection with the muscle relaxant,
      rocuronium bromide. Committed suicide or sound alike medication error?

PMID- 19838449
TI  - Correlation between pain relief and patient satisfaction.

PMID- 19838450
TI  - Effects of obesity on inflammation and lipid profile of obese women.

PMID- 19838451
TI  - Correlation between acupuncture and left-handed patients after stroke.

PMID- 19838452
TI  - Clinical patterns of cutaneous tuberculosis at King Fahad Hospital of the
      University in Al-Khobar, Saudi Arabia over 13 years.

PMID- 19838453
TI  - Serodiagnosis of cutaneous leishmaniasis in the Syrian Arab Republic.

PMID- 19838454
TI  - Risk factors and outcome in extended spectrum beta-lactamase producing
      Escherichia coli and Klebsiella pneumoniae bacteremia.

PMID- 19838455
TI  - Smoking in Saudi Arabia.

PMID- 19838456
TI  - Hydrogen peroxide induces a specific DNA base change profile in the presence of
      the iron chelator 2,2' dipyridyl in Escherichia coli.
AB  - Pretreatment of Escherichia coli cultures with the iron chelator 2,2'-dipyridyl
      (1 mM) protects against the lethal effects of low concentrations of hydrogen
      peroxide (<15 mM). However, at H(2)O(2) concentrations equal to or greater than
      15 mM, dipyridyl pretreatment increases lethality and mutagenesis, which is
      attributed to the formation of different types of DNA lesions. We show here that
      pretreatment with dipyridyl (1 mM) prior to challenge with high H(2)O(2)
      concentrations (>or=15 mM) induced mainly G:C-->A:T transitions (more than 100X
      with 15 mM and more than 250X with 20 mM over the spontaneous mutagenesis rate)
      in E. coli. In contrast, high H(2)O(2) concentrations in the absence of dipyridyl
      preferentially induced A:T-->T:A transversions (more than 1800X and more than
      300X over spontaneous mutagenesis for 15 and 20 mM, respectively). We also show
      that in the fpg nth double mutant, the rpoB gene mutation (RifS-RifR) induced by
      20 mM H(2)O(2) alone (20X higher) was increased in 20 mM H(2)O(2) and dipyridyl
      treated cultures (110X higher), suggesting additional and/or different lesions in
      cells treated with H(2)O(2) under iron deprivation. It is suggested that, upon
      iron deprivation, cytosine may be the main damaged base and the origin of the pre
      mutagenic lesions induced by H(2)O(2).

PMID- 19838457
TI  - Myocardial infarction caused by coronary artery injury after a blunt chest
      trauma.
AB  - We report the case of a 29-year-old man, victim of a car accident, who suffered a
      severe blunt chest trauma, with evolving congestive heart failure. He had
      previously had a good overall health status, with no symptoms of cardiovascular
      disease. At the initial assessment, the electrocardiogram showed Q waves in the
      precordial leads and the echocardiogram disclosed severe left ventricular
      dysfunction. Coronary angiogram showed a proximal left anterior descending
      coronary artery lesion, with anterior wall akinesis on contrast-enhanced
      ventriculography. A Thallium-201 single photon emission computed tomography
      (SPECT) showed no viability. He remained on medical treatment with good
      evolution.

PMID- 19838458
TI  - Hormonal replacement and cardiovascular disease: a guideline against the
      evidence.

PMID- 19838459
TI  - Late involution of obstructive rhabdomyoma of the mitral valve.

PMID- 19838460
TI  - Dobutamine stress echocardiography-induced broken heart syndrome (Takotsubo
      Syndrome).
AB  - We report a case of dobutamine stress echocardiography-induced Takotsubo syndrome
      in a 76-year-old hypertensive patient with clinical complaints of chest pain in
      an elective visit to the cardiologist. Dobutamine-stress-echocardiography was
      requested to rule out chest pain of coronary origin. During the test, at peak
      exercise, echocardiogram showed apical akinesia and electrocardiogram showed ST
      segment elevation in D1, AVL, and V2. The patient was hospitalized and underwent
      coronary angiography, which showed normal coronary arteries and left ventricular
      apical ballooning. During follow-up, the patient's condition remained stable,
      with regression of the manifestations 21 days after the initial presentation.

PMID- 19838461
TI  - Intraoperative transesophageal echocardiography in septal hypertrophic
      cardiomyopathy.
AB  - We report the case of a patient with septal hypertrophic cardiomyopathy
      undergoing surgical correction in which the use of intraoperative transesophageal
      echocardiography permitted the planning of the surgical approach and an immediate
      knowledge of the surgical outcome.

PMID- 19838462
TI  - Continuing education and environment in the center of action.

PMID- 19838463
TI  - Association of fitness and waist circumference with hypertension in Brazilian
      elderly women.
AB  - BACKGROUND: The protective effect of cardiorespiratory fitness, regardless of
      obesity, has been recognized in adults. However, this association is still not
      clear in elderly individuals. OBJECTIVE: To analyze the association between
      hypertension and cardiorespiratory fitness in 1,064 elderly Brazilian women.
      METHODS: Central obesity was estimated by waist circumference and
      cardiorespiratory fitness by the 6-minutes walk test. ANOVA one way, chi-square
      and logistic regression were used for the statistical analysis. RESULTS: The
      prevalence of hypertension was 53.9%. The central obesity group had higher odds
      for hypertension when compared with the non-central-obesity group, in the same
      cardiorespiratory fitness group. Furthermore, both the central obesity and non
      central obesity groups had a progressive increase in the odds ratio for
      hypertension, from the highest to lowest fitness groups, indicating an inverse
      relation between fitness and central adiposity. The non-central obesity group had
      the lowest odds ratios (OR), 1.49 (95%IC 0.97-2.28) and 1.54 (95%IC 0.94-2.51);
      whereas the central obesity group had an OR of 2.08 (95%IC 1.47-2.93), 2.79
      (95%IC 1.79-4.33) and 3.09 (95%IC 1.86-5.12). CONCLUSION: Our findings indicated
      that the waist circumference measurement is a strong predictor of hypertension
      and suggested that the protective effect of cardiorespiratory fitness can be
      extended to elderly women, even to those with central obesity.

PMID- 19838464
TI  - Maternal-fetal outcome and prognosis of cardiac surgery during pregnancy.
AB  - BACKGROUND: Cardiac surgery improves the maternal prognosis in cases refractory
      to medical therapy. However, it is associated with risks to the fetus when
      performed during pregnancy. OBJECTIVE: To analyze maternal-fetal outcome and
      prognosis related to cardiac surgery performed during pregnancy and puerperium.
      METHODS: The outcome of 41 gestations of women undergoing cardiac surgery during
      pregnancy and puerperium was studied. Fetal cardiotocography was performed
      throughout the procedure in patients with gestational age above 20 weeks.
      RESULTS: Mean maternal age was 27.8 +/- 7.6 years; there was a predominance of
      patients with rheumatic valve disease (87.8%), of whom 15 (41.6%) underwent
      reoperation due to prosthetic valve dysfunction. Mean extracorporeal circulation
      time was 87.4+/- 43.6 min and hypothermia was used in 27 (67.5%) cases. Thirteen
      (31.7%) mothers experienced no events and gave birth to live healthy newborns.
      Postoperative outcome of the remaining 28 (68.3%) pregnancies showed: 17 (41.5%)
      maternal complications and three (7.3%) deaths; 12 (29.2%) fetal losses, and four
      (10%) cases of neurological malformation, two of which progressed to late death.
      One patient was lost to follow-up after surgery. Nine (21.9%) patients underwent
      emergency surgery, and this variable was correlated with maternal prognosis
      (p<0.001) CONCLUSION: Cardiac surgery during pregnancy allowed survival of 92.7%
      of the mothers, and 56.0% of the patients who presented cardiac complications
      refractory to medical therapy gave birth to healthy children. Worse maternal
      prognosis was correlated with emergency surgery.

PMID- 19838466
TI  - Body mass index as a marker of dyslipidemia in children.
AB  - BACKGROUND: Obesity is very frequently associated with conditions such as
      dyslipidemia and diabetes. OBJECTIVE: To verify the diagnostic value of the cut
      off points proposed by the International Obesity Task Force (IOTF) and Conde &
      Monteiro (C&M) for the screening and identification of dyslipidemia in children
      between 10 and 12 years of age. METHODS: The Body Mass Index (BMI) of 374
      children of the school network of the city of Santa Maria-RS was ascertained. The
      children were selected in a stratified manner from a population of 4,083
      children. Lipid levels (reference standard) were determined by means of analysis
      of total cholesterol (TC), LDL-C, HDL-C and triglycerides (TG). The cut-off
      points of the IOTF and C&M were used to classify the BMI. Descriptive statistics
      and analysis of sensitivity and specificity were employed. RESULTS: There was a
      statistical difference in excess weight prevalence between both proposals (24.7%
      and 28.6% for IOTF and C&M, respectively). A variation was observed in
      sensitivity (33% to 83%) and specificity (62% to 80%) between the cut-off points
      as to the detection of dyslipidemia. The percentage of false negatives was lower
      than the percentage of false positives. CONCLUSION: The proposals may be used to
      screen elevated TC and LDL-C in male individuals. Either the IOTF or the C&M
      classification may be used to identify subjects without dyslipidemia, as these
      proposals presented high specificity.

PMID- 19838465
TI  - Subclinical coronary artery disease in patients with type 1 Diabetes Mellitus
      undergoing hemodialysis.
AB  - BACKGROUND: In patients with type 1 diabetes mellitus, atherosclerosis occurs
      earlier in life and coronary artery disease (CAD) constitutes the major cause of
      death. OBJECTIVE: Evaluate the prevalence and anatomic characteristics of
      coronary artery disease (CAD) in type 1 diabetic patients with chronic renal
      failure undergoing hemodialysis. METHODS: This is a descriptive study of 20
      patients with type 1 diabetes mellitus undergoing hemodialysis without known CAD.
      CAD was assessed by quantitative coronary angiography (QCA) and intravascular
      ultrasound (IVUS). QCA was performed in all lesions >30%, visually. All proximal
      18-mm segments of the coronary arteries were analyzed by IVUS. All other coronary
      segments with stenosis >30% were also analyzed. RESULTS: Angiography detected 29
      lesions >30% in 15 patients (75%). Eleven (55%) of the lesions were >50% and 10
      (50%) >70%. Thirteen patients had all 3 major arteries interrogated by IVUS.
      Atherosclerosis was present in all patients and in all 51 proximal 18-mm segments
      analyzed. The mean vessel diameter of these segments was significantly larger at
      the IVUS than at the QCA, for all vessels. IVUS images of 25 (86.2%) of the 29
      lesions >30% were obtained. Fibrotic plaques were common (48%) and 60% had
      intermediate vessel remodeling. CONCLUSION: CAD was present in all vessels of all
      type 1 diabetic patients undergoing hemodialysis. These findings are in agreement
      with other autopsy, angiography and IVUS studies. Additionally, they indicate the
      need for additional epidemiological and imaging studies to better understand and
      treat such a complex and serious clinical condition affecting young people.

PMID- 19838467
TI  - Lipoprotein (a) is associated with basal insulin levels in patients with type 2
      Diabetes Mellitus.
AB  - BACKGROUND: It has not been clearly established whether insulin
      resistance/deficiency leads directly to atherogenesis or through its association
      with other risk factors such as lipoprotein(a) [Lp(a)]. OBJECTIVE: This project
      aimed at studying the association between basal insulin, lipids and
      lipoprotein(a) levels in patients with type 2 diabetes mellitus. METHODS: Fasting
      blood samples were analyzed for Insulin, Lipoprotein(a), total cholesterol (TC),
      triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density
      lipoprotein cholesterol (HDL-C), glucose and glycosylated hemoglobin (HbA1c)
      levels in 60 patients with type 2 Diabetes Mellitus (DM) and 28 healthy subjects.
      We divided patients into two groups based on basal insulin levels: > or = 10
      microIU/ml and < 10 microIU/ml. RESULTS: Insulin levels were higher in diabetic
      versus control individuals [p < 0.05]. TC (p< 0.01), LDL-C (p< 0.05), TC/HDL
      ratio (p< 0.01) and TG levels (p< 0.05) were higher and HDL- C levels were
      significantly lower (p < 0.001) in both diabetic groups as compared to control.
      Lp(a) levels were significantly higher in both diabetic groups, when compared to
      the control group. Lp(a) levels were significantly lower in diabetics with basal
      insulin > or =10 microIU/ml when compared to those with basal insulin < 10
      microIU/ml (p < 0.05). Regression analysis revealed a significant relationship of
      Lp(a) with insulin levels (r = 0.262, p < 0.05) and Insulin Glucose ratio (r =
      0.257, p < 0.05). CONCLUSION: Lp(a) levels correlate inversely with insulin
      levels in Type 2 diabetic patients. Lp(a) may be one of the cardiovascular risk
      factor in type 2 diabetic patients with longer duration of DM.

PMID- 19838468
TI  - Role of lipoperoxidation in the remodeling intensification induced by beta
      carotene after infarction.
AB  - BACKGROUND: The mechanisms involved in the biggest remodeling caused by the post
      infarct beta-carotene are unknown. OBJECTIVE: To analyze the role of
      lipoperoxidation in the ventricular remodeling after infarct of the myocardium in
      rats supplemented with beta-carotene. METHODS: Rats were infarcted and divided
      into two groups: C (control) and BC (500mg/kg/regimen). After six months,
      echocardiogram and biochemical evaluation were performed. The t test was used,
      with 5% significance. RESULTS: The animals from BC group presented highest means
      of the diastolic (C = 1.57 +/- 0.4 mm(2)/g, BC = 2.09 +/- 0.3 mm(2)/g; p < 0.001)
      and systolic (C = 1.05 +/- 0.3 mm(2)/g, BC = 1.61 +/- 0.3 mm(2)/g; p < 0.001)
      areas of LV, which were adapted according to the rat's body weight. The systolic
      function of LV, evaluated by the area variation fraction, was lower in the
      animals supplemented with beta-carotene (C = 31.9 +/- 9.3%, BC = 23.6 +/- 5.1%; p
      = 0.006). The animals supplemented with beta-carotene presented higher values of
      the E/A relation (C = 2.7 +/- 2.5, BC = 5.1 +/- 2.8; p = 0.036). No differences
      were found between the groups concerning the cardiac levels of the GSH (C = 21 +/
      8 nmol/mg of protein, BC = 37 +/- 15 nmol/mg of protein; p = 0.086), GSSG (C =
      0.4 (0.3-0.5) nmol/g of protein, BC = 0.8 (0.4-1.0; p = 0.19) of protein; p =
      0.246) and lipoperoxides (C = 0.4 +/- 0.2 nmol/mg of tissue, BC = 0.2 +/- 0.1
      nmol/mg of tissue; p = 0.086). CONCLUSION: The highest remodeling in infarcted
      rats supplemented with beta-carotene does not depend on the lipoperoxidation.

PMID- 19838469
TI  - Validation of the Portuguese version of the Minnesota Living with Heart Failure
      Questionnaire.
AB  - BACKGROUND: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is an
      important measurement instrument for assessing the quality of life of heart
      failure patients. Despite being largely used within our context, the
      questionnaire had not yet been translated and validated into the Portuguese
      language. OBJECTIVE: Of this study was to translate and validate the Portuguese
      version of the MLHFQ for use in heart failure patients. METHODS: Forty patients
      with heart failure (30 men, LVEF 30+/-6%, 55% ischemic etiology, classified as
      NYHA I to III), clinically stable and on optimized drug therapy underwent maximal
      cardiopulmonary stress testing to assess their physical capacity. Right after the
      test, the MLHFQ duly translated into Portuguese was administered by the same
      investigator. The NYHA functional classification was provided by the medical
      team. RESULTS: The Portuguese version of the MLHFQ had the same structure and
      metrics of the original version. There was no difficulty in the administration of
      the questionnaire or in the patient's understanding of the questions. The
      Portuguese version of the MLHFQ was consistent with peak VO2, duration of the
      cardiopulmonary test, and NYHA functional classification. There was no difference
      in the score mean for the questionnaire between the group of patients with
      ischemic etiology and the group with non-ischemic etiology. CONCLUSION: The
      Portuguese version of the MLHFQ proposed in this study proved to be valid for
      heart failure patients, and constitutes a new and important instrument for
      assessing quality of life.

PMID- 19838470
TI  - Blood pressure measurement during aerobic exercise: subsidies for cardiac
      rehabilitation.
AB  - BACKGROUND: Institutional documents recommend that hemodynamic variables--heart
      rate (HR) and systolic (SAP) and diastolic arterial pressure (DAP)--be routinely
      controlled at the aerobic part of supervised exercise sessions for coronary
      disease patients. OBJECTIVE: a) to determine the pattern and reproducibility of
      the blood pressure (BP) throughout 15 minutes of physical exercise at constant
      and moderate intensity; and b) to compare the BP measurement obtained with
      digital and conventional device during the exercise. METHODS: Thirty adult
      individuals of both sexes (65+/-11 yrs) were assessed for 15 minutes during lower
      limb cycle ergometry and the BP was measured every 2 minutes, between the 3rd and
      the 13th minutes, using a Tango digital sphygmomanometer (Suntech, USA) and in
      the 14th minute, using a mercury column sphygmomanometer. Seven days later, at
      similar time of the day, six individuals had the test repeated to evaluate
      reproducibility. RESULTS: Whereas the DAP did not vary throughout the exercise (p
      > 0.05), SAP increased from the 3rd to 7th minute (146+/-4.1 versus 158+/-4.5
      mmHg, p<0.05) and thereafter remained practically constant. The digital and
      conventional measurements showed a strong correlation - r = 0.83 for SAP and 0.84
      for DAP - with no differences for SAP (163+/-4.5 versus 162+/-4.3 mmHg; p >0.05)
      and a small difference for DAP (72+/-2.4 versus 78+/-2.3 mmHg; p<0.05).
      CONCLUSION: For exercises of moderate and constant intensity in a cycle ergometer
      with a 15-minute duration, BP measurements must be carried out from the 7th
      minute on. The digital measurements with the Tango equipment and those obtained
      with the conventional mercury-column sphygmomanometer were, for clinical
      purposes, very similar and reproducible.

PMID- 19838471
TI  - Dobutamine-stress echocardiography in asymptomatic patients with aortic
      regurgitation.
AB  - BACKGROUND: Decreased contractile reserve may already be present in asymptomatic
      patients with aortic regurgitation and normal ejection fraction (EF), thus
      indicating the need for frequent and accurate assessments of the left ventricular
      function for the early detection of systolic dysfunction. OBJECTIVE: To analyze
      if increments in EF with low dose dobutamine could predict surgery and/or death
      in patients with aortic regurgitation. METHODS: Dobutamine-stress
      echocardiography was performed in 24 patients with aortic regurgitation in order
      to analyze whether EF increments at low dobutamine doses could predict the need
      for surgery and/or death in this group of patients. RESULTS: Mean age was 37.8+/
      16.8 years and 16 patients (66%) were male. EF increased from a mean baseline
      value of 62.3+/-7.9% to 71.5+/-10.5% at a dobutamine dose of 20 microg/kg/min
      (p<0.001). The patients were followed-up for 36.6+/-20.1 months; two patients
      died (one of cardiovascular death) and five underwent cardiac surgery. Baseline
      EF was correlated with surgery and death in the follow-up of patients.
      CONCLUSION: Baseline EF was correlated with surgery or death in the follow-up of
      young patients with aortic regurgitation. However, the percentage increase in EF
      at low dobutamine doses did not allow us to predict events in these patients.

PMID- 19838472
TI  - Postoperative atrial fibrillation after cardiac surgery.
AB  - Atrial fibrillation (AF) is an arrhythmia frequently seen in the postoperative
      period of cardiac surgery. In this context, it is associated with the presence of
      comorbidities, longer length of hospital stay, and higher costs related to
      surgery. The mechanisms involved in the genesis of AF in the postoperative period
      of cardiac surgery (AFPO) are different from those causing paroxysmal AF.
      Knowledge of these mechanisms permits the use of efficient measures to reduce the
      incidence of this arrhythmia. According to recommendations of the literature,
      treatment is efficient and safe, because the rates of reversion to sinus rhythm
      are high and complications are reduced, and it is not associated with a high
      frequency of side effects.

PMID- 19838473
TI  - Case 3/2009--a 75-year-old man with heart failure after myocardial infarction and
      ventricular aneurysm.

PMID- 19838474
TI  - Ventricular fibrillation during sport activity successfully treated.
AB  - Survival after out-of-hospital cardiopulmonary arrest is estimated at less than
      5%. We report a case of ventricular fibrillation during sports activity.
      Cardiopulmonary resuscitation was initiated early by a layperson, and
      defibrillation was successfully performed within less than three minutes, with an
      automated external defibrillator. The public access to defibrillation programs
      has increased the survival after out-of-hospital ventricular fibrillation. We
      should encourage the training of laypeople in relation to the use of automated
      external defibrillators and the Basic Life Support program by stimulating their
      implementation in places where large numbers of people gather or where people are
      at a high risk of sudden death, as is the case of sports centers.

PMID- 19838475
TI  - Prinzmetal's angina.
AB  - This syndrome is due to focal spasm of an epicardial coronary artery, leading to
      severe myocardial ischemia. Although it is frequently thought that the spasm
      occurs in arteries without stenosis, many Prinzmetal patients have spasm adjacent
      to atheromatous plaques. The exact cause of the spasm has not been well defined,
      but it may be related to the hypercontractility of the vascular smooth muscle due
      to vasoconstrictor mitogens, leukotrienes, or serotonin. In some patients, it is
      a manifestation of a vasospastic disorder and it is associated with migraine,
      Raynaud's phenomenon, or aspirin-induced asthma. We present a case associated
      with transient ST-segment depression.

PMID- 19838476
TI  - Echocardiographic features of non-compaction cardiomyopathy: missed and
      misdiagnosed disease.
AB  - Non-compaction cardiomyopathy is a rare disease, anatomically characterized by a
      prominent trabecular pattern and deep intertrabecular recesses. Its clinical
      manifestations include severe left ventricular dysfunction, arrhythmias, systemic
      embolism, and sudden death. In this report, two cases of patients of different
      ages with non-compaction cardiomyopathy are described: a male schoolboy whose
      pathology was associated with mitral stenosis and regurgitation and a 50-year-old
      female with history of high blood pressure and cardiac failure.

PMID- 19838477
TI  - Prenatal diagnosis of left ventricular aneurysm and diverticulum.
AB  - We report two cases of localized left ventricular (LV) protrusion, an entity that
      has been described in the literature as aneurysm or diverticulum. Both cases had
      different outcomes from those previously reported. Little is known on the
      incidence and natural history of these rare anomalies, whose progression may be
      asymptomatic or lead to severe complications and death in the prenatal period.
      The therapeutic approach should be customized.

PMID- 19838478
TI  - Assessment of sphygmomanometers: a proposal for excellence in blood pressure
      measurement.

PMID- 19838479
TI  - Resident graduated at the institute of will: the requisites - aspiration,
      movement and prevailing over.

PMID- 19838481
TI  - European National Society Cardiovascular Journals background, rationale and
      mission statement of the "Editors' Club" (task force of the European Society of
      Cardiology).

PMID- 19838482
TI  - The two Brazils and the treatment of acute myocardial infarction.

PMID- 19838483
TI  - Prevalence of metabolic syndrome in an elderly community: comparison between
      three diagnostic methods.
AB  - BACKGROUND: The prevalence of the metabolic syndrome (MS) has shown wide
      variation in different studies, depending on the population sample and the
      diagnostic criteria used. The prevalence of MS tends to be higher with the
      diagnostic criteria of the International Diabetes Federation (IDF). OBJECTIVE: To
      compare the prevalence of MS using different criteria in an elderly community.
      METHODS: This was a cross-sectional population-based study conducted in the city
      of Novo Hamburgo - RS - Brazil, in which 378 elderly individuals, aged 60 years
      or over (252 women and 126 men) participated. The prevalence of MS was estimated
      using the National Cholesterol Education Program - Adult Treatment Panel III
      (NCEP ATPIII) (2001), the revised NCEP ATPIII (2005) and the IDF diagnostic
      criteria. RESULTS: The prevalence of MS increased progressively as we used the
      NCEP ATP III, the revised NCEP ATP III and the IDF criteria, with values of
      50.3%, 53.4% and 56.9% respectively. The progressive increase in the prevalence
      of MS using the three criteria occurred in both genders, with a higher prevalence
      among women, with rates of 57.1%, 59.9% and 63.5% with the NCEP ATP III, the
      revised NCEP ATP III, and the IDF criteria, respectively. CONCLUSION: The use of
      the IDF criteria resulted in a higher prevalence of MS in comparison to the
      prevalence found with the NCEP ATP III criteria and the revised NCEP ATP III
      criteria. The prevalence of MS was higher among women, regardless of the criteria
      used.

PMID- 19838484
TI  - Echocardiographic evaluation of patients undergoing mitral valve replacement with
      crossed papillopexy.
AB  - BACKGROUND: Techniques for mitral valve replacement with preservation of the
      subvalvular apparatus have proven their superiority, and crossed papillopexy is a
      new technical option which, besides allowing Preservation of the anatomical
      structures, provides contractility support and protection to the myocardium
      during ventricular diastole. The technique requires further studies that document
      its results. OBJECTIVE: To evaluate the left atrial and ventricular function by
      Doppler echocardiography in patients who have undergone mitral valve replacement
      with crossed papillopexy. METHODS: Fifteen patients underwent mitral valve
      replacement, 9 (60%) of them male, and the mean age was 45.7 years. As to the
      etiology of aortic valve disease, nine (60%) cases were degenerative, three (20%)
      were rheumatic, two (13.3%) were ischemic, and one patient (6.7%) had infectious
      endocarditis. After closure of the atriotomy and anatomical evaluation of the
      valvar apparatus, the anterior leaflet was detached from the annulus and
      centrally split in halves, each one with its complex tendinous chords attached to
      the opposing commissure by its medial extremity. Biological (13 cases) or
      mechanical prosthetic valves were implanted and secured with separate stitches.
      Reduction of the valvar annulus was performed in patients with dilated
      cardiomyopathy. Patients underwent clinical and Doppler echocardiographic
      examinations before surgery and six months after the procedure. RESULTS: All
      patients were clinically stable at discharge. A significant reduction in
      ventricular and atrial diameters was demonstrated (p< 0.001) without impairment
      of the entry and exit points of the left ventricle. CONCLUSION: Mitral valve
      replacements performed with the crossed papillopexy technique showed favorable
      results with a positive effect on the recovery of left atrial and ventricular
      morphology.

PMID- 19838485
TI  - Increased mortality and morbidity due to acute myocardial infarction in a public
      hospital, in Feira de Santana, Bahia.
AB  - BACKGROUND: Factors related to socioeconomic status and health care quality and
      management may influence mortality and morbidity rates due to acute myocardial
      infarction (AMI). OBJECTIVE: To compare mortality and morbidity in patients with
      AMI hospitalized in public and private hospitals. METHODS: An observational
      study, with comparison groups. Clinical evaluation on admission, and recording of
      diagnostic, therapeutic and evolution data until discharge or death. Comparison
      of clinical characteristics by univariate analysis followed by bivariate
      analysis, evaluating the combination of predictors with death and morbidity
      (Killip> I), SPSS, version 13.0. RESULTS: 150 patients were evaluated, 63 (42.0%)
      of private hospitals and 87 (58.0%) of public hospitals, with 63.1% and 62.1% of
      males, aged 61.1 +/- 13.8 and 60.0 +/- 11.6 years, respectively. The mortality
      from AMI was 19.5% in public hospitals vs 4.8% in private hospitals (p = 0.001),
      and morbidity (Killip class> I) was 34.3% in public hospitals vs 15.0% in private
      hospitals (p = 0.012). There was a significant difference between public and
      private patients, due to lower family income and education (70.1% with one to two
      salaries vs 19.0%, p <0.001, and 49.4% of illiterates vs 6.3%, p <0.001,
      respectively ); late arrival at the hospital (HAT> 1 hour: 76.9% vs 48.6%, p =
      0.003); and a longer period of time before being medicated (AMT > 15 minutes:
      47.1% vs 8.0%; p <0.001); ICU for 8% of the patients in public hospitals vs 94%
      in private hospitals; and thrombolysis for 20.6% vs 54.0%, respectively (p
      <0.001). CONCLUSION: Mortality and morbidity were greater among public patients,
      which presented more serious conditions, arrived later at the hospital and
      received lower quality treatment.

PMID- 19838486
TI  - TIMI risk score for acute myocardial infarction according to prognostic
      stratification.
AB  - BACKGROUND: The TIMI (Thrombolysis in Myocardial Infarction) risk score is
      derived from clinical trial involving patients who are eligible for fibrinolysis.
      As the risk profiles of these cases differ from those found in non-selected
      populations, it is important to review the applicability of the score in usual
      clinical conditions. OBJECTIVES: To evaluate the management and clinical
      evolution of hospital inpatients with acute myocardial infarction, according to
      risk stratification by the TIMI score. METHODS: We evaluated, retrospectively,
      103 cases of acute myocardial infarction with ST-segment elevation admitted to
      the Hospital Nossa Senhora da Conceicao - Tubarao, in 2004 and 2005. The cases
      were analyzed in three risk groups according to the TIMI score. RESULTS: The
      hospital mortality after infarction was 17.5%. In the low-risk group there was no
      death. The mortality was 8.1% in the medium risk group and 55.6% in the high-risk
      group. The risk of death in cases of high risk was 14.1 times higher than in the
      cases of medium and low risk (95% CI = 4.4 to 44.1 and p <0.001). The chance of
      receiving fibrinolytic was 50% lower in the high-risk group in relation to the
      low risk group (95% CI = 0.27 to 0.85, p = 0.004). CONCLUSION: There was a
      progressive increase in mortality and incidence of in-hospital complications
      according to the stratification by the TIMI score. High risk patients received
      thrombolytic less frequently than the patients at low risk.

PMID- 19838487
TI  - Lipid profile, cardiovascular risk factors and metabolic syndrome in a group of
      AIDS patients.
AB  - BACKGROUND: Since the advent of AIDS, the anti-HIV therapy has developed
      significantly, including the highly active antiretroviral therapy (HAART) and the
      disease acquired a chronic characteristic. However, after the introduction of
      HAART, several metabolic alterations were observed, mainly related to the lipid
      profile. OBJECTIVES: to evaluate and compare lipid profiles, analyze
      cardiovascular risk, describe the prevalence of metabolic syndrome in AIDS
      patients with or without HAART. METHODS: Over an 18-month period, 319 patients
      treated at outpatient clinics in the city of Sao Paulo, Brazil were selected.
      RESULTS: The final sample included 215 patients receiving HAART and 69 HAART
      naive patients. The mean age was 39.5 years, and 60.9% were males. The main
      cardiovascular risk factors were smoking (27%), hypertension (18%) and family
      history of atherosclerosis (40%). Mean total cholesterol, HDL-cholesterol,
      triglycerides and glucose were higher in the HAART group than in the non-HAART
      group (205 vs 180 mg/dl, 51 vs 43 mg/dl, 219 vs 164 mg/dl and 101 vs 93 mg/dl
      respectively; p < 0.001 for all). According to the Framingham risk score, the
      cardiovascular risk was moderate to high in 11% of the patients receiving HAART
      and 4% of the HAART-naive patients. According to the Adult Treatment Panel III
      definition, the metabolic syndrome was observed in 13% and 12% of the patients
      with or without HAART, respectively. CONCLUSIONS: Although the mean values for
      total cholesterol, HDL-c and triglycerides were higher in the HAART group, a
      higher cardiovascular risk was not identified in the former. The prevalence of
      metabolic syndrome was comparable in both groups.

PMID- 19838488
TI  - Correlation between metabolic and body composition variables in female
      adolescents.
AB  - BACKGROUND: Analysis of metabolic alterations and body composition in
      adolescents. OBJECTIVES: To study the correlation of serum levels of lipids,
      glycemia, insulin, homocysteine, HOMA-IR and blood pressure among themselves and
      with body variables. METHODS: Data concerning glycemia, total cholesterol and
      fractions (LDL, HDL and VLDL), triacylglycerols, insulin, homocysteine and blood
      pressure were measured in 100 adolescents at the age range of 14 to 17 years, who
      had already had menarche and attended the public schools in Vicosa, state of
      Minas Gerais, Brazil. The percentage of body fat (%BF) was evaluated by
      horizontal bioimpedance. RESULTS: In relation to nutritional status, 83%, 11% and
      6%, respectively were eutrophic (EU), presented overweight/overweight risk
      (OW/OR) or low weight (LW) (CDC/NCHS, 2000) and 61% presented high percentage of
      BF. Total cholesterol presented the highest percentage of inadequacy (57%),
      followed by HDL (50%), LDL (47%) and triacylglycerols (22%). Inadequacy in 11%,
      9%, 5% and 4% were observed in relation to insulin resistance, insulin, blood
      pressure and glycemia, respectively. For total cholesterol, insulin, HOMA-IR and
      nutritional state, OW/OR>LW (p<0.05). For body composition and nutritional
      status, OW/OR>EU>LW (p <0.001). Some positive and strong correlations were found
      between BMI and the anthropometrical measures estimating the % of total BF, as
      well as central distribution, except for the waist/hip ratio. The %BF was
      correlated with insulin levels (r=0.303; p <0.001) and HOMA-IR (r=0.281;
      p<0.001). CONCLUSIONS: Some metabolic alterations, most often related with excess
      weight and body fat as well as insulin resistance were found, reinforcing the
      importance of specific programs directed at the adolescent health.

PMID- 19838489
TI  - Prospective double-blind crossover study of Camellia sinensis (green tea) in
      dyslipidemias.
AB  - BACKGROUND: Epidemiological studies have established an association between
      dyslipidemias and atherosclerosis. Nutritional therapy is a key point in the
      prevention strategy for individuals who present with risk factors for
      atherosclerotic disease. OBJECTIVES: To investigate the effects of green tea
      (Camellia sinensis) in patients with dyslipidemias. METHODS: The study included
      33 patients aged between 21 and 71 years who had a low-fat diet (25-35% of total
      calories and 200 mg of cholesterol per day). They were randomized for two
      sequential treatments: 250-mg capsules of green tea dry extract or placebo for a
      total period of 16 weeks; each patient received green tea (Camellia sinensis) for
      eight weeks and placebo for another eight weeks. RESULTS: Baseline lipid values
      (mg/dL) were: HDL-cholesterol 60.7 +/- 7.3; total cholesterol 255 +/- 30.9; LDL
      cholesterol 158.8 +/- 29.0; triglycerides 169.0 +/- 61.3 and Apo-B 120.2 +/-
      18.9. Mean lipid variations induced by the use of green tea (Camellia sinensis)
      showed a 3.9% reduction (p = 0.006) in total cholesterol concentrations and a
      4.5% reduction (p = 0.026) in LDL-cholesterol. The intake of green tea did not
      significantly influence HDL-cholesterol, triglyceride, and Apo-B levels. Non
      significant results were found in the assessment of blood lipids (total
      cholesterol and LDL-cholesterol) with the use of placebo. CONCLUSION: A
      beneficial effect of green tea (Camellia sinensis) was demonstrated, with a
      significant reduction of total cholesterol and LDL-cholesterol levels in eight
      weeks, in the patients studied.

PMID- 19838490
TI  - Predictors of hospital mortality in hemodynamically stable patients with
      pulmonary embolism.
AB  - BACKGROUND: Pulmonary embolism is associated with high mortality in patients with
      hypotension or circulatory shock. However, the association between some clinical
      variables and mortality is still unclear in hemodynamically stable patients.
      OBJECTIVES: To derive an in-hospital mortality risk stratification model in
      hemodynamically stable patients with pulmonary embolism. METHODS: This is a
      prospective multicenter cohort study of 582 consecutive patients admitted in
      emergency units or intensive care units with clinically suspected pulmonary
      embolism and whose diagnosis was confirmed by one or more of the following tests:
      pulmonary arteriography, spiral CT angiography, magnetic resonance angiography,
      Doppler echocardiography, pulmonary scintigraphy, or venous duplex scan. Data on
      demographics, comorbidities and clinical manifestations were collected and
      included in a logistic regression analysis so as to build the prediction model.
      RESULTS: Overall mortality was 14.1%. The following parameters were identified as
      independent death risk variables: age > 65 years, bed rest > 72h, chronic cor
      pulmonale, sinus tachycardia, and tachypnea. After risk stratification,
      mortalities of 5.4%, 17.8%, and 31.3% were found in the low, moderate and high
      risk subgroups, respectively. The model showed 65.5% sensitivity and 80%
      specificity, with a 0.77 area under the curve. CONCLUSION: In hemodynamically
      stable patients with pulmonary embolism, age > 65 years, bed rest > 72h, chronic
      cor pulmonale, sinus tachycardia and tachypnea were independent predictors of in
      hospital mortality. However, further validation of the prediction model in other
      populations is required so that it can be incorporated into the clinical
      practice.

PMID- 19838491
TI  - Association between initial and final transient heart rate responses in exercise
      testing.
AB  - BACKGROUND: The rest-exercise-rest transition is accompanied by rapid and slow
      heart rate (HR) changes modulated by the branches of the autonomic nervous
      system. Vagal participation seems to be distinct in these different transitions.
      Additionally, it is methodologically difficult to determine the best moment and
      how to measure resting HR. OBJECTIVE: To determine the association between
      initial (rapid and slow) and final transient HR responses during exercise,
      considering different forms of measuring resting HR. METHODS: We retrospectively
      studied 103 non-athlete adults (76 males) who underwent 4-second exercise test to
      obtain the rapid transient HR response as measured by the cardiac vagal index
      (CVI), and completed a maximal cardiopulmonary exercise test in exactly 10
      minutes. HR changes were measured in the first few minutes of exercise (DeltaHR)
      and recovery (dHR). RESULTS: Modest associations were found between CVI and the
      three forms of measuring DeltaHR, r between 0.27 and 0.31 (p<0.05), and a more
      significant association between dHR and CVI, r=0.53 (p<0.05). The means of the
      three measurements of resting HR were different (p<0.05) and showed only
      reasonable correlations between them (r between 0.64 and 0.76; p<0.05).
      CONCLUSION: It is important to standardize the measurement of resting HR for the
      analysis of transient HR responses; small or moderate association between the
      results of the different transients suggests that partially distinct autonomic
      mechanisms are involved and that their measurements may provide different and
      potentially complementary clinical information.

PMID- 19838492
TI  - Association of body mass index and insulin resistance with metabolic syndrome in
      Brazilian children.
AB  - BACKGROUND: The clustering of cardiovascular risk factors called metabolic
      syndrome occurs in both children and adults. Insulin resistance and obesity are
      usual parts of the picture, but their joint effects on the onset of the syndrome
      remains somewhat debatable. OBJECTIVE: The purpose of the current study was to
      examine the relationship of the body mass index (BMI) and insulin resistance with
      the metabolic syndrome (MS) in children. METHODS: We studied 109 children, 55
      boys and 54 girls, between 7 and 11 years of age (55 obese, 23 overweight and 31
      controls). The weight status of each child was defined based on BMI/age ratio.
      Blood glucose, HDL, triglycerides and insulin were measured using fasting
      samples. Blood pressure was measured twice. The metabolic syndrome was defined
      according to the NCEP ATP III criteria. RESULTS: The diagnosis of the MS was only
      found in obese children. The greater frequency of MS and of many of its
      components have been found in the children classified above the third quartile of
      the HOMA index, which is consistent with an association between insulin
      resistance and cardiovascular risk factors among the Brazilian children.
      CONCLUSION: The present study shows that obesity and insulin resistance are
      likely to play a role in the development of cardiovascular risk factors in
      children since the prevalence of classic risk factors was higher in the upper BMI
      and HOMA percentiles.

PMID- 19838493
TI  - The effects of trimetazidine on heart rate variability in patients with heart
      failure.
AB  - BACKGROUND: Reduced measures of heart rate variability (HRV) have been shown to
      be related with prognosis in heart failure. Chronic administration of
      trimetazidine in addition to the conventional therapy has been shown to improve
      functional class and left ventricular functions of heart failure patients.
      OBJECTIVE: To assess the effects of trimetazidine on HRV in optimally treated
      patients with heart failure of ischemic origin. METHODS: Trimetazidine 20 mg
      three times/day was added to therapy of 30 patients with heart failure being
      treated with angiotensinogen converting enzyme inhibitors or angiotensin receptor
      blockers, carvedilol, spironolactone, digitalis and furosemide. The etiology of
      heart failure was coronary artery disease in all patients. Patients were
      evaluated with echocardiography and 24-hour heart rate variability analysis
      before and 3 months after addition of trimetazidine. RESULTS: Mean left
      ventricular ejection fraction (LVEF) significantly increased after the addition
      of trimetazidine (33.5+/-5.1% to 42.5+/-5.8%, p<0.001). Of the HRV parameters,
      SDNN (97.3+/-40,1 to 110.5+/-29,2 msecs, p=0.049) and SDANN (80.5+/-29,0 to
      98.3+/-30,5 msecs) were significantly increased after trimetazidine treatment.
      Baseline SDNN was significantly correlated with baseline LVEF (r=0.445, p=0.023,
      p=0.008) and the increment in SDNN was correlated with increase in LVEF (r=0.518,
      p=0.007). CONCLUSIONS: Adding trimetazidine to optimal medical therapy in
      patients with heart failure of ischemic origin may improve heart rate variability
      in association with improved left ventricular ejection fraction.

PMID- 19838494
TI  - Quality of life and clinical indicators in heart failure: a multivariate
      analysis.
AB  - BACKGROUND: In Heart Failure (HF), special attention must be given not only to
      objective or isolated aspects, but also to the patient's health self-perceptions.
      Subjective aspects can help healthcare providers understand and better treat HF.
      OBJECTIVE: The objective of this study was to evaluate the simultaneous effects
      of clinical indicators of HF on the Quality-of-Life (QOL). METHODS: We
      investigated, through a multivariate analysis, the QOL of 101 Brazilian HF
      outpatients using the Minnesota Living with Heart Failure Questionnaire
      (including subscales) and its correlation to clinical and physiological variables
      such as age, ethnicity, gender, echocardiogram parameters, body mass index, mean
      blood pressure at rest, time since diagnosis, Functional Classification according
      to the NYHA, functional capacity by a Specific Activity Scale, comorbidities,
      Framingham Score of Cardiac Risk (CR), Lung Function Test (spirometry) and Body
      Composition. RESULTS: QOL showed significant univariate correlations to the
      echocardiogram: ejection fraction (p=0.0415), left ventricular diastolic diameter
      (LVDD) (p=0.004), left ventricular systolic diameter (LVSD) (p=0.0001);
      comorbidities (p=0.002) and Lung Function Test: Forced Vital Capacity (FVC)
      (p<0.0001), Forced Expiratory Volume in the 1st second (FEV1) (p<0.0001) and
      Maximal Voluntary Ventilation (MVV) (p=0.001). In the multivariate analysis, the
      backward stepwise protocol detected important simultaneous influent variables
      (r(2)=0.60): gender (0.000178), ethnicity (p<0.00001), LVSD (P<0.00001), CR
      (p=0.000002), FVC (p=0.002027), FEV1 (p<0.00001) and MVV (p=0.00001). CONCLUSION:
      Gender, ethnicity, LVSD, CR, FVC, FEV1 and MVV are independent predictors of HF
      patients' QOL. Simultaneously, they are responsible for about 60% of the QOL
      variance. Biopsychosocial aspects could contribute to patient and health
      professional expectations and treatment results.

PMID- 19838495
TI  - Conventional ventricular stimulation effects on patients with normal ventricular
      function.
AB  - BACKGROUND: The stimulation of the right ventricle (RV) may be deleterious in
      patients with ventricular dysfunction; however there is little evidence about the
      impact of this stimulation in patients with normal ventricular function.
      OBJECTIVES: To assess the clinical and laboratory evolution of patients with
      normal ventricular function submitted to implant of artificial cardiac pacemaker
      (PM). METHODS: 16 patients enrolled according to the following inclusion
      criteria: normal ventricular function defined by echocardiogram and presence of
      upper ventricular stimulation > 90% (generator telemetry assessment) submitted to
      a PM implant were prospectively studied. The following parameters were assessed:
      Functional Class (FC), walk test, BNP levels, echocardiography evaluation
      (conventional and intraventricular dyssynchrony) and quality of life test (SF36).
      The patients were assessed after 10 (t1), 120 (t2) and 240 days (t3). Data was
      compared throughout time according to ANOVA. Multiple comparisons of means were
      performed through Tukey's test. RESULTS: Among the assessed data, the following
      did not present significant statistic variation (p> 0.05): functional class, BNP
      levels, conventional echocardiographic parameters, intraventricular dyssynchrony
      (tissue Doppler). The walk test (between t2 and t3) and the time between septal
      contraction and LV posterior wall showed worsening (p<0.05), although they did
      not meet the dyssynchrony criteria. The quality of life assessment (SF36) showed
      improvement in the functional capacity, social aspects, and general status sub
      items. CONCLUSION: After 8 months, patients with normal ventricular function did
      not show clinical (FC and SF36) or laboratory alterations (conventional
      echocardiography, dyssynchrony parameters and BNP levels); however, there was a
      worsening in the walk test.

PMID- 19838496
TI  - Bleeding during oral anticoagulant therapy: warning against a greater hazard.
AB  - BACKGROUND: Bleeding is one of the main concerns in patients undergoing oral
      anticoagulation therapy. OBJECTIVE: To investigate the determinant causes of
      bleeding in patients undergoing oral anticoagulant therapy. METHODS: A total of
      360 patients with atrial fibrillation (AF) undergoing oral anticoagulant (ACo)
      therapy, with a target INR of 2.0-3.5, were followed prospectively for a period
      of 48 +/- 7.2 months. The patients were evaluated on average every 30 days and
      were investigated regarding the presence of associated pathology that could lead
      to bleeding. RESULTS: A total of 338 patients participated in the present study.
      Of these, 210 (62.13%) were females. Mitral stenosis was present in 218 patients
      (64.4%), a mitral biological prosthesis in 64 (18.9%) and mitral valve failure in
      56 (16.5%) patients. Bleeding occurred in 65 patients (19.2%), being severe in 7
      (10%) patients. In 38/65 patients, a new associated disease was identified, which
      facilitated bleeding. An associated disease was identified in 100% of the
      patients with bleeding within the therapeutic range, against 49.05% of associated
      disease diagnosis in those with an INR > 3.5 (p=0.001). CONCLUSION: The diagnosis
      of a local disease associated to the bleeding was frequent among those patients
      undergoing oral anticoagulant therapy (58.5%). There was an association between
      bleeding with an INR within the therapeutic range (INR=2.0-3.5) and the diagnosis
      of a pathology predisposing to bleeding (p<0.001). It is mandatory to investigate
      the cause of bleeding in patients undergoing oral anticoagulant therapy,
      especially if the INR is within the therapeutic range.

PMID- 19838497
TI  - Heart failure with normal ejection fraction: new diagnostic criteria and
      pathophysiological advances.
AB  - Heart failure (HF) is a highly prevalent complex cardiovascular syndrome, and its
      clinical presentation is usually associated with ventricular dilatation,
      decreased contractility and reduced left ventricular ejection fraction (EF).
      However, in the past two decades studies have demonstrated that many patients
      with signs and symptoms of HF have normal EF (higher than 50%). The great
      challenge for doctors lies in the identification of patients presenting heart
      failure with normal ejection fraction (HFNEF) and this challenge seems to be
      mainly related to the high complexity of the syndrome and to the lack of a
      standardized method to confirm or exclude the diagnosis that could be used in the
      daily clinical practice. Unlike in heart failure with reduced ejection fraction
      (HFREF) in which one single parameter - EF lower than 50%, is sufficient to
      confirm the diagnosis of the syndrome, in HFNEF different diastolic indexes have
      been used to characterize the presence or absence of diastolic dysfunction (DD).
      The purpose of this review is to show new concepts related to the diastolic
      function that will help understand the cardiovascular pathophysiology of HFNEF,
      and to discuss the new guideline of the European Society of Cardiology for the
      diagnosis and exclusion of HFNEF based on cardiac function indices obtained using
      tissue Doppler imaging (TDI) and natriuretic peptide determination.

PMID- 19838498
TI  - Competitive sports for children and adolescents: should an electrocardiogram be
      required in the pre-participation physical examination?
AB  - The growing number of children and adolescents, aged 7 to 17 years, that
      participate in competitive sports requires preventive medical care. The pre
      participation physical examination (PPE) requires appropriate medical knowledge
      to insure safe medical clearance. Recent sudden death events related to sports
      practice have raised doubts concerning the need for a medical evaluation based on
      medical tests, which due to the delay in its implementation may result in
      demotivation and abandonment of the sports practice. This is a review study,
      including data collected during a period of 30 years at the Olympic Training and
      Research Center (COTP) of the Municipal Secretary of Sports of Sao Paulo, where
      future athletes are identified, socially included and trained; and the objective
      of the study was to evaluate the need for the involvement of medical
      organizations in the preparation of a EPP protocol for the cardiovascular
      assessment of this population, according to the Brazilian reality. We had no
      normative standard, and so we relied on data collected from protocols that were
      established by other countries, but we defined which conduct to be taken with
      each of our individuals.

PMID- 19838499
TI  - Percutaneous coronary intervention for stable patients: is there any benefit
      beyond symptom relief?
AB  - The indications for percutaneous coronary intervention (PCI) continue to evolve
      because of the steady improvement in technology, broadened patient and lesion
      selection criteria, and new evidence from clinical trials. Considerable
      controversy was generated by the main results from the Clinical Outcomes
      Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, in
      which no difference in long-term outcome was reported for stable patients with
      coronary disease randomized to an initial strategy of PCI plus optimal medical
      therapy versus optimal medical therapy alone. In patients with chronic stable
      angina, medical therapy remains the cornerstone and should be optimized for all
      patients, while the major achievable goals of PCI are to affect symptoms, either
      by decreasing or preventing them, reducing the need for subsequent procedures and
      relieving ischemia. In patients with stable coronary artery disease, however, no
      reduction in death or myocardial infarction has been observed, and these
      limitations of PCI in this clinical setting need to be emphasized. The message
      from the COURAGE trial may be refined based on recently presented nuclear and
      angiographic sub-studies, such that patients with substantial residual ischemia
      on optimal medical therapy should be considered for crossover PCI, as it is
      associated with greater likelihood of death and myocardial infarction. However,
      those findings need to be confirmed by prospective evaluation before being widely
      accepted by the interventional community.

PMID- 19838500
TI  - Case 5/2009: eight-month old infant with mitral insufficiency due to hammock
      mitral valve with frank heart failure.

PMID- 19838503
TI  - Different measurements of the sagittal abdominal diameter and waist perimeter in
      the prediction of HOMA-IR.
AB  - BACKGROUND: The correlation between the increase in visceral fat and insulin
      resistance makes the sagittal abdominal diameter and the waist perimeter as
      potential tools for the prediction of insulin resistance. OBJECTIVE: To assess
      the reproducibility of different measurements of the sagittal abdominal diameter
      and the waist perimeter and analyze the discriminating power of the measurements
      when predicting insulin resistance. METHODS: A total of 190 adult males were
      studied. The sagittal abdominal diameter (smallest girth, larger abdominal
      diameter, umbilical level and midpoint between the iliac crests) and the waist
      perimeter (umbilical level, smallest girth, immediately above the iliac crest and
      midpoint between the iliac crest and the last rib) were measured at four
      different sites. Insulin resistance was assessed by the homeostasis model of
      assessment-insulin resistance (HOMA-IR) index. RESULTS: All measurements
      presented an intraclass correlation of 0.986-0.999. The sagittal abdominal
      diameter measured at the smallest girth (r=0.482 and AUC=0.739+/-0.049) and the
      waist perimeter measured at the midpoint between the last rib and the iliac crest
      (r=0.464 and AUC=0.746+/-0.05) presented the highest correlations with the HOMA
      IR and the best discriminating power for HOMA-IR according to the ROC analysis
      (p<0.001). CONCLUSION: The sagittal abdominal diameter and waist perimeter showed
      to be highly reproducible and the sagittal abdominal diameter (smallest girth)
      and waist perimeter (midpoint between the iliac crest and the last rib) presented
      the best performance when predicting HOMA-IR. Further studies in other groups of
      the Brazilian population must be carried out to allow the use of these indicators
      of insulin resistance in the population as a whole, following standardized
      procedures.

PMID- 19838504
TI  - Movement-induced heart rate changes in epileptic and non-epileptic seizures.
AB  - Heart rate changes are common in epileptic and non-epileptic seizures. Previous
      studies have not adequately assessed the contribution of motor activity on these
      changes nor have evaluated them during prolonged monitoring. We retrospectively
      evaluated 143 seizures and auras from 76 patients admitted for video EEG
      monitoring. The events were classified according to the degree of ictal motor
      activity (severe, moderate and mild/absent) in: severe epileptic (SE, N=17),
      severe non-epileptic (SNE, N=6), moderate epileptic (ME, N=28), moderate non
      epileptic (MNE, N=11), mild epileptic (mE, N=35), mild non-epileptic (mNE, N=33)
      and mild aura (aura, N=13). Heart rate increased in the ictal period in severe
      epileptic, severe non-epileptic, moderate epileptic and mild epileptic events
      (p<0.05). Heart rate returned to baseline levels during the post ictal phase in
      severe non-epileptic seizures but not in severe epileptic patients. Aura events
      had a higher baseline heart rate. A cut-off of 20% heart rate increase may
      distinguish moderate epileptic and mild epileptic events lasting more than 30
      seconds. In epileptic seizures with mild/absent motor activity, the magnitude of
      heart rate increase is proportional to the event duration. Heart rate analysis in
      seizures with different degrees of movement during the ictal phase can help to
      distinguish epileptic from non-epileptic events.

PMID- 19838505
TI  - MRI findings in the diagnosis and monitoring of Rasmussen's encephalitis.
AB  - Rasmussen's encephalitis is a devastating syndrome of multifocal brain
      dysfunction and focal seizures. Magnetic resonance (MR) findings, associated with
      clinical data and electroencephalogram (EEG), may indicate the diagnosis and
      could be an indicative of prognosis. We studied 5 patients with Rasmussen's
      encephalitis, assessing clinical history and MR images. All patients had
      refractory focal seizures with a predominant motor component associated with
      hemispheric atrophy, that was proportional to severity of disease and
      neurological deficits in these patients. Gray and white matter abnormal signal on
      T2 MR images were found in patients who had hemiparesis. It was not related to
      the duration of the disease but to aggressiveness. MR proton spectroscopy in
      severe disease showed lactate and choline increase and decreased NAA, reflecting
      neuronal and axonal loss, gliosis and elevated membrane turnover and recent -
      crisis (not controlled). MR studies, in addition to help in diagnosis, may be
      useful for monitoring metabolic changes and progression of disease in Rasmussen's
      encephalitis.

PMID- 19838506
TI  - An epidemiologic study of headaches in Brazilian schoolchildren with a focus on
      pain frequency.
AB  - The purpose of this study was to assess the prevalence and frequency of the
      headaches in Brazilian schoolchildren. A cross-sectional study was conducted
      between March and November 2004 in Sao Jose do Rio Preto, Sao Paulo State,
      Brazil. A sample of 5,232 children from elementary schools was selected using
      proportional stratified sampling method. To collect data, a questionnaire was
      handed out in the schools to the schoolchildren to be answered by parents or
      guardians. From the total answers received, 84.2% reported headache complaints
      during the last year. There were significant complaint differences between males
      and females. Females were reported as having more frequent headaches than males
      with daily ones occurring twice as many times. A greater headache frequency was
      also reported for increasing age. The study has shown that headache prevalence
      was high, with a predominantly higher frequency (monthly, weekly and daily) with
      girls and older age groups.

PMID- 19838507
TI  - Hyperglycemia in pediatric head trauma patients: a cross-sectional study.
AB  - OBJECTIVE: To verify the prevalence of acute hyperglycemia in children with head
      trauma stratified by the Glasgow coma scale (GCS). METHOD: A prospective cross
      sectional study carried out with information from medical records of pediatric
      patients presenting with head injury in the emergency room of a referral
      emergency hospital during a one year period. We considered the cut-off value of
      150 mg/dL to define hyperglycemia. RESULTS: A total of 340 children were included
      and 60 (17.6%) had admission hyperglycemia. Hyperglycemia was present in 9% of
      mild head trauma cases; 30.4% of those with moderate head trauma and 49% of
      severe head trauma. We observed that among children with higher blood glucose
      levels, 85% had abnormal findings on cranial computed tomography scans.
      CONCLUSION: Hyperglycemia was more prevalent in patients with severe head trauma
      (GCS <8), regardless if they had or not multiple traumas and in children with
      abnormal findings on head computed tomography scans.

PMID- 19838508
TI  - Neurological congenital malformations in a tertiary hospital in south Brazil.
AB  - BACKGROUND: Congenital anomalies are one of the main causes of morbidity and
      mortality among infants. The involvement of the central nervous system (CNS)
      occurs in 21% of cases. OBJECTIVE: To identify incidence of CNS malformations and
      associated factors in newborns at a Terciary Hospital of Porto Alegre. METHOD:
      Case-control study conducted between 2000 and 2005 based on the Latin American
      Collaborative Study of Congenital Malformations database. RESULTS: Among 26,588
      births registered in this period, 3.67% presented with malformations (IC=95%;
      3.44-3.9), being 0.36% of the CNS (IC=95%,(0.29-0.43)). The most common CNS
      malformation was meningomielocele (10.4%). Young maternal age (p=0.005); low
      birth weight (p=0.015); large cephalic perimeter (p=0.003); post term birth
      (p=0.000) and low APGAR indexes at the 1st and 5th minutes were associated with
      CNS malformations. CONCLUSION: We found an incidence of CNS malformations similar
      as compared to literature.

PMID- 19838510
TI  - Correlation between fatigue and self-esteem in patients with multiple sclerosis.
AB  - OBJECTIVE: To assess the possible association of fatigue with self-esteem in
      multiple sclerosis (MS) patients. METHOD: Thirty patients were prospectively
      assessed. None of them presented moderate or severe depression or anxiety and
      their degree of disability was low (EDSS<or=3.5). They had been clinically stable
      for at least three months and had been receiving the same medication for at least
      six months. Socioeconomic level was assessed. Severity of fatigue and self-esteem
      were evaluated using specific, validated scales. Patients with moderate to severe
      anxiety and/or depression were excluded. RESULTS: Low self-esteem correlated with
      fatigue (p=0.01), but not with any other variables, such as age, gender, EDSS, MS
      duration, number of relapses, mild depression and/or anxiety. CONCLUSION: Greater
      severity of fatigue in MS correlates with low self-esteem, thus suggesting that
      this chronic complaint that affects so many patients can interfere with the way
      in which they see and value themselves.

PMID- 19838509
TI  - The effect of functional limitations and fatigue on the quality of life in people
      with multiple sclerosis.
AB  - The purpose of this study was to determine the effect of functional limitations
      and fatigue on the quality of life (QoL) in people with multiple sclerosis (MS).
      A descriptive case series study at Lagoa Hospital - Rio de Janeiro, Brazil was
      carried. The main outcome measurements were demographic variables, QoL (SF-36
      v.1), disability (EDSS), motor function of the upper limb (Box & Blocks test),
      Tone (Modified Ashworth Scale), gait (Hauser ambulatory index) and fatigue
      (Fatigue Severity Scale). Sixty one patients fulfilled the study criteria. The
      mean age of patients was 39 years and 74% of patients were female. The most of
      cases presented mild disability (EDSS<3.5). A decrease was found in all domains
      of QoL. It was found association between physical functioning and the variables
      of EDSS, fatigue, lower limb tone and gait. Gait, disability, hypertonia of the
      lower limbs and fatigue negatively affected QoL in people with MS.

PMID- 19838511
TI  - Restless legs syndrome: study of prevalence among medical school faculty members.
AB  - The aim of this study was to assess the prevalence of idiopathic restless legs
      syndrome (RLS) and its correlations in a sample of Medical School faculty
      members. A transversal study was conducted at a Medical School in the south of
      Brazil included 78 faculty members. The subjects answered to a structured
      questionnaire specific to RLS diagnosis and the Epworth and the Stanford scales
      to measure daytime sleepiness. Severity of the disease was also evaluated. The
      variables were analyzed to statistical significance. RLS was diagnosed in 10.25%
      of the subjects evaluated and most were women (62.5%). The prevalence of daytime
      sleepiness was significantly greater among the subjects suffering from RLS
      (p=0.04). RLS subjects were significantly younger than the group without the
      syndrome (p=0.02). RLS had a considerable prevalence in the sample studied.
      Daytime sleepiness and young age showed an important correlation to this
      syndrome, as other potential factors were not confirmed.

PMID- 19838512
TI  - Parkinsonism and AIDS: a clinical comparative study before and after HAART.
AB  - In 2002, after analyzing 28 HIV-positive patients with movement disorders we
      emphasized the decreasing not only of Parkinsonism but also of other involuntary
      movements in HIV patients in the last few years. The objective of this study is
      to compare the clinical results between HIV-positive patients with Parkinsonism
      before and after HAART. In 14 years (1986-1999) 2,460 HIV-positive patients were
      seen in our Hospital 14 (0.6%) of which presented with Parkinsonism. Eight years
      after (2000-2007) 970 HIV positive patients were seen and only two (0.2%) had
      Parkinsonism. We conclude that after the introduction of HAART there was an
      evident decrease in AIDS-related Parkinsonism.

PMID- 19838513
TI  - Validation of the Brazilian version of the Berg balance scale for patients with
      Parkinson's disease.
AB  - BACKGROUND: Changes in balance occur with the progression of Parkinson's disease
      (PD). OBJECTIVE: To validate the Brazilian version of the Berg Balance Scale
      (BBS) for PD patients, determining its reliability and internal consistency and
      correlating it with PD-specific instruments. METHOD: We evaluated 53 patients
      (M/F 37/16, mean age+/-SD, 62+/-7.9 years) with PD (mean+/-SD, 7.8+/-4.4 years).
      Unified Parkinson's Disease Rating Scale (UPDRS), Schwab and England Scale (SandE
      , Hoehn and Yahr Staging Scale (HY) and BBS were used to assess patients.
      Statistical analyses for inter-rater reliability, internal consistency and
      correlations among BBS, UPDRS, SandE and HY were performed. RESULTS: The mean
      scores+/-SD on UPDRS and BBS were, respectively, 41.6+/-17.8 and 47.2+/-8.2. The
      median on SandE and HY scales were 80% and 2.5, respectively. The BBS presented a
      high intra-class correlation coefficient (ICC=0.84) and internal consistency
      (Cronbrach's alpha=0.92). There was a statistically significant correlation
      between BBS and disease duration (r(s)= -0.520, p<0.001), UPDRS subscales II and
      III (r(s)= -0.467, p=0.011; r(s)= -0.374, p=0.046, respectively), stage of
      disease (HY; r(s)= -0.507, p<0.001) and the activities of daily living (SandE;
      r(s)=0.492, p<0.001). CONCLUSION: The BBS is a promising tool for the assessment
      of balance in PD, correlating with the stage of disease and the level of
      independence.

PMID- 19838514
TI  - Validity and reliability of the screening test for Alzheimer's disease with
      proverbs (STADP) for the elderly.
AB  - The prevalence Alzheimer's disease with age compromises memory, language,
      executive functions, constructive praxis and abstraction, requiring early
      evaluation with standardized tests. OBJECTIVE: To validate the Screening Test for
      Alzheimer's Disease with Proverbs (STADP), elaborated using pieces from the
      proverb memory game. METHOD: The test contains three stages (A: short-term
      memory, B: executive functions and language and C: episodic memory). The sample
      consisted of 91 elderly individuals with minimum age of 60 years and one year of
      schooling, CDR of one or zero, cared for at specialized services of UFPE, HGA and
      private institutions. Sociodemographic data, habits and health perception were
      assessed. Among the tests used were MMSE (convergent validity) and GDS
      (discriminating). RESULTS: A good correlation with standardized test was found,
      acceptable internal consistency (0.71), cutoff point for schooling of 6.49 (low)
      (80% and 77.8%) and 8.66 (high) (84.6% and 86.1%); Kappa coefficient of 1
      (p=0.000) inter-rater consistency. CONCLUSION: STADP is a valid test for
      screening Alzheimer's disease.

PMID- 19838515
TI  - The relationship between working memory and apraxia of speech.
AB  - The present study aimed to verify the relationship between working memory (WM)
      and apraxia of speech and explored which WM components were involved in the motor
      planning of speech. A total of 22 patients and 22 healthy adults were studied.
      These patients were selected according to the following inclusion criteria: a
      single brain lesion in the left hemisphere, presence of apraxia of speech and
      sufficient oral comprehension. This study involved assessment of apraxia of
      speech and evaluation of working memory capacity. The performance of apraxic
      patients was significantly poorer than that of controls, where this reached
      statistical significance. The study concluded that participants with apraxia of
      speech presented a working memory deficit and that this was probably related to
      the articulatory process of the phonoarticulatory loop. Furthermore, all apraxic
      patients presented a compromise in working memory.

PMID- 19838516
TI  - Short-term prognosis for speech and language in first stroke patients.
AB  - OBJECTIVE: To evaluate the factors that can influence evolution of communication
      after a first stroke. METHOD: Thirty-seven adult patients were evaluated for
      speech and language within 72 hours after a single first-ever ischemic brain
      injury and later on. Patients who were comatose, with decompensated systemic
      diseases, or history of chronic alcoholism or illicit drug use were not included.
      Brain CT and/or 2T-MR exams were solicited for topographic correlation. Size of
      infarct was classified as large or small according to the TOAST classification.
      RESULTS: Patients who survived had lesser chances of presenting with aphasia or
      dysarthria 3 months after the stroke if the infarct size was small (p=0.017).
      Gender, age, schooling, aphasia subtype, infarct side and topography were non
      significant in our sample. Subjects with global aphasia or lone cortical
      dysarthria had a slower evolution. CONCLUSION: Brain injury size was the most
      influential factor for neurological outcome at 3 months post-stroke.

PMID- 19838517
TI  - Verbal language spontaneous recovery after ischemic stroke.
AB  - OBJECTIVE: To analyze the spontaneous recovery of the verbal language on patients
      who have had an ischemic stroke. METHOD: Retrospective analysis of 513 medical
      records. We characterize referring aspects for data identification, language
      deficit, spontaneous recovery and speech therapy. RESULTS: The average age was
      62.2 years old (SD= +/-12.3), the average time of academic experience was 4.5
      years (SD=+/-3.9), 245 (47.7%) patients presented language disturbance, 166
      (54.0%) presented spontaneous recovery, from which 145 (47.2%) had expression
      deficit (p=0.001); 12 (3.9%) had comprehension deficit and 9 (2.9%) had both
      expression and comprehension deficit. Speech therapy was carried with 15 patients
      (4.8%) (p=0.001). CONCLUSION: The verbal language spontaneous recovery occurred
      in most of the patients being taken care of at the stroke out clinic, and
      expression disturbance was the most identified alteration. As expected, the left
      hemisphere was associated with the deficit and smoking and pregressive stroke
      were the language alteration primary associated factors.

PMID- 19838518
TI  - Mouth breathing children have cephalometric patterns similar to those of adult
      patients with obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To determine whether mouth breathing children present the same
      cephalometric patterns as patients with obstructive sleep apnea syndrome (OSAS).
      METHOD: Cephalometric variables were traced and measured on vertical lateral
      cephalometric radiographs. The cephalometric measurements of 52 mouth and 90 nose
      breathing children were compared with apneic patients. The children had not
      undergone adenoidectomy or tonsillectomy and had not had or were not receiving
      orthodontic or orthopedic treatment. RESULTS: Mouth breathing children showed
      same cephalometric pattern observed in patients with OSAS: a tendency to have a
      retruded mandible (p=0.05), along with greater inclination of the mandibular and
      occlusal planes (p<0.01) and a tendency to have greater inclination of the upper
      incisors (p=0.08). The nasopharyngeal and posterior airway spaces were greatly
      reduced in mouth breathing children, as observed in patients with apnea (p<0.01).
      CONCLUSION: Mouth breathing children present abnormal cephalometric parameters
      and their craniofacial morphology resembles that of patients with OSAS.

PMID- 19838519
TI  - Pain in tropical spastic paraparesis/HTLV-I associated myelopathy patients.
AB  - OBJECTIVE: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (TSP/HAM) is
      a chronic myelopathy, and pain has been mentioned as a frequent sensory symptom
      in this condition. The authors aimed at analyzing this symptom in a TSP/HAM
      patients series. METHOD: For this, 46 patients were analyzed considering
      demographic and clinical characteristics and complaint of pain as to verbal
      description, time of onset and classification, correlated with the degree of
      motor disability and type of pain. RESULTS: Among the 46 TSP/HAM patients, 28
      (60.8%) complained of pain, predominant in the early phase of the disease. Most
      of the patients exhibited neuropathic characteristics of pain, correlated with
      increased motor disability. CONCLUSION: Pain in TSP/HAM patients is a frequent
      and early symptom, and the neuropathic type is predominant (57.1%) and paralleled
      with increased incapacitation. The pathogenic involvement of cytokines may
      possibly be involved in the meaning of this symptom in this condition.

PMID- 19838520
TI  - Evaluation of arthrodesis and cervical alignment in the surgical results of
      cervical discectomy using polymethylmetacrylate.
AB  - BACKGROUND AND OBJECTIVES: Surgical treatment of cervical radiculopathy with or
      without myelopathy is a controversy issue, although anterior discectomy is the
      most common form of treatment. METHOD: We present the evaluation of the
      arthrodesis' rate and cervical alignment in 48 patients with cervical
      degenerative disease (CDD) submitted to anterior cervical discectomy with
      interposition of polymethylmetacrylate (PMMA). Odom and Nurick scales were used
      to evaluation of functional status before and after surgery. Cervical spine X
      rays were used to access arthrodesis and alignment, at least 2 years after the
      procedure. RESULTS: Excellent and good results (Odom I and II) were obtained in
      91% of the patients with radiculopathy and in 69% of those with myelopathy. Using
      the chi square test of independence (1% of significance), there was no
      association between excellent and good clinical results with the presence of
      arthrodesis verified in cervical X-rays. The presence of cervical alignment had
      association with good results, whereas the misalignment was associated with
      unfavorable outcomes. Two patients died: one cervical hematoma and other from
      graft migration with cord compression. CONCLUSIONS: Cervical alignment was more
      important than fusion to achieve good surgical results in CDD.

PMID- 19838521
TI  - Cerebral biopsy: comparison between frame-based stereotaxy and neuronavigation in
      an oncology center.
AB  - Treatment of intracranial tumoral lesions is related to its correct histological
      diagnostic. We present a retrospective analysis of 32 patients submitted to 36
      cerebral biopsies using neuronavigation and 44 patients using frame-based
      stereotaxy. Mean age was 46.6 and 49.3 years old respectively. Sex distribution
      in both groups was 50% for each. Most of lesions were lobar in both groups.
      Diagnostic yielding was 91.7% and 83.4%, respectively (p=0.26). We found in the
      postoperative CT scans intracranial hemorrhages in 13.8% cases of the first group
      and 9.8% cases in the second. Most of them were mild post-operative hemorrages in
      the biopsy site. There was one death related to the procedure in each group.
      Astrocytomas and metastatic adenocarcinomas were the most frequent diagnosis.
      Diagnostic yielding and the number of postoperative hemorrhage and death were
      similar on both groups and the same found in the literature.

PMID- 19838522
TI  - Persistent trigeminal artery: angio-tomography and angio-magnetic resonance
      finding.
AB  - The trigeminal artery (TA) is the most common embryonic carotid-vertebrobasilar
      anastomosis to persist into adulthood. It typically extends from the internal
      carotid artery to the basilar artery. Persistent primitive arteries are usually
      found incidentally, but are often associated with vascular malformation, cerebral
      aneurysm and, in case of TA, with trigeminal neuralgia. We present one patient
      with TA as a cause of trigeminal neuralgia and in other three as an incidental
      finding, on TC and MR angiograms.

PMID- 19838523
TI  - Nemaline myopathy: clinical, histochemical and immunohistochemical features.
AB  - Nemaline myopathy (NM) is a congenital disease that leads to hypotonia and
      feeding difficulties in neonates. Some cases have a more benign course, with
      skeletal abnormalities later in life. We analyzed a series of eight patients with
      NM obtained from a retrospective analysis of 4300 muscle biopsies. Patients were
      classified as having the typical form in five cases, intermediate form in two
      cases and severe form in one case. Histochemical analysis showed mixed rods
      distribution in all cases and predominance of type I fibers in five cases.
      Immunohistochemical analysis showed abnormal nebulin expression in all patients
      (four heterogeneous and four absent), homogeneous desmin expression in four
      cases, strongly positive in three and absent in one, fast myosin expression in a
      mosaic pattern in six cases and absent in two cases. There was no specific
      relation between these protein expression patterns and the clinical forms of NM.

PMID- 19838524
TI  - Autosomal dominant HMSN with proximal involvement: new Brazilian cases.
AB  - We report four Brazilian siblings with Autosomal Dominant Hereditary Motor
      Sensory Neuropathy with Proximal Dominant Involvement (HMSN-P), a rare form of
      HMSN, that was characterized by proximal dominant muscle weakness and atrophy
      onset after the age of 30 years, fasciculation, arreflexia and sensory
      disturbances with autosomal dominant inheritance. Electrophysiological study and
      sural nerve biopsy were in the accordance with axonal sensory motor
      polyneuropathy and laboratorial analysis disclosed serum lipids and muscle
      enzymes abnormalities. Our report is the first done by a group outside Japan,
      where the disease initially seemed to be restricted and stressed the phenotypic
      variability from the original report.

PMID- 19838525
TI  - Traumatic lesions of internal saphenous nerve and branches.
AB  - OBJECTIVE: To show a rare lesion that sometimes simulates vascular disorder of
      the lower extremities. METHOD: Three patients were operated and the follow-up
      period was eight months, the surgical technique was neurotomy of the
      infrapatellar and descendent branches. RESULTS: In two cases there were almost
      total pain resolution, and in other case improvement only. CONCLUSION: Surgical
      treatment yields good results in this type of internal saphenous nerve lesion,
      and could be useful as an alternative to conservative treatment.

PMID- 19838526
TI  - Incidence of antibodies in cerebrospinal fluid of patients with multiple
      sclerosis treated with interferon beta.

PMID- 19838527
TI  - Complex hyperkinetic movement disorders: an unusual presentation in multiple
      sclerosis.

PMID- 19838528
TI  - Overlap of Bickerstaff encephalitis and Guillain-Barre syndrome in a patient with
      systemic lupus.

PMID- 19838529
TI  - Migrainous infarction as a complication of sporadic hemiplegic migraine in
      childhood.

PMID- 19838530
TI  - Progressive supranuclear palsy-like syndrome induced by amiodarone and
      flunarizine.

PMID- 19838531
TI  - Frameless stereotactic navigation for intraoperative localization of infectious
      intracranial aneurysm.

PMID- 19838532
TI  - The increasing female participation in authorship of articles published in
      neurology in Brazil.
AB  - During the past four decades the participation of women in medicine has increased
      dramatically. This study is focused on the women's participation in authorship of
      articles published in the Arquivos de Neuro-Psiquiatria, the official Journal of
      the Brazilian Academy of Neurology. The articles were analyzed according to the
      number of articles and sex of both first and the senior (last) authors. The data
      were collected from 1945 to 2005. A total of 950 articles were published in this
      period. The proportion of women serving as first authors increased from 2.8% to
      36.6% and the proportion serving as senior authors increased from 2.8% to 23.8%
      (1945-2005).

PMID- 19838533
TI  - Brainstem cavernous malformations: a review with two case reports.
AB  - Central nervous system (CNS) cavernous malformations (CMs) are developmental
      malformations of the vascular bed with a highly variable clinical course due to
      their dynamic nature. We present one case of 'de novo' brainstem cavernous
      malformation after radiation therapy adding to the increasing number of reported
      cases in the medical literature, and the case of a pregnant patient with
      symptomatic intracranial hemorrhage related to brainstem CMs to illustrate the
      complex nature in management of these patients, followed by a review of clinical
      and radiographic characteristics. CMs account for 8-15% of all intracranial and
      intraspinal vascular malformations. Although traditionally thought to be
      congenital in origin, CMs may present as acquired lesions particularly after
      intracranial radiation therapy. Clinical manifestations are protean and surgical
      treatment should be considered for patients with progressive neurologic deficits.

PMID- 19838534
TI  - May the best friend be an enemy if not recognized early: possible role of omega-3
      against cardiovascular abnormalities due to antipsychotics in the treatment of
      autism.
AB  - Autism spectrum disorders (ASD) are neurodevelopment disorders that cause severe
      and pervasive impairment in socialization, communication, and behavior. Although
      the availability of antipsychotic treatment in ASD has expanded, we will be very
      careful with side effects of these pharmacological agents. Following this
      reasoning, emerging data indicate that some antipsychotics may be associated with
      cardiovascular adverse events (e.g., QT interval prolongation), suggesting that
      this could be correlated to sudden death. Quite interesting, substantial evidence
      from epidemiological and case-control studies indicates that omega-3 reduces the
      risk of cardiovascular mortality, particularly sudden cardiac death. In
      accordance to the above mentioned findings, as omega-3 fatty acids per se have a
      direct cardiovascular protective role, our paper hypothesized that omega-3 fatty
      acids supplementation in ASD patients treated with atypical antipsychotic drugs
      may reduce cardiac arrhythmias and hence sudden cardiac death.

PMID- 19838535
TI  - Epilepsy and sudden unexpected death in epilepsy?: eat more fish! A group
      hypothesis.
AB  - Epilepsy is the commonest serious neurological disorder and individuals with
      epilepsy are at higher risk of death than the general population and sudden
      unexpected death in epilepsy (SUDEP) is the most important direct epilepsy
      related cause of death. Potential pathomechanisms for SUDEP are unknown, but it
      is very probable that cardiac arrhythmias during and between seizures play a
      potential role. The ultimate goal of SUDEP research is to develop methods to
      prevent it and nutritional aspects such as omega-3 fatty acid deficiency may have
      an interesting role in this scenario. Omega-3 fatty acids reduce the risk of
      cardiovascular mortality and are important for treating or preventing some
      neurological diseases, including epilepsy. A dietary modification or nutritional
      supplements increasing the ingestion of omega-3 fatty acids may help to ''save
      the brain'.

PMID- 19838536
TI  - Neuropsychiatry of Parkinson's disease.
AB  - Parkinson's disease (PD) is traditionally regarded as a movement disorder. In
      recent years, however, non-motor symptoms have been considered significant
      factors of disability at all stages of the illness. Behavioral and psychological
      symptoms or neuropsychiatric syndromes associated with PD are frequent and may
      represent a challenge in the management of these patients. They include anxiety,
      depression, psychosis, sleep, sexual and impulse control disorders, apathy and
      cognitive dysfunction. Their pathogenesis in PD is complex, involving
      neurodegenerative, drug-related and psychological mechanisms. We will review the
      current knowledge of this growing field, also focusing on the management of
      theses syndromes.

PMID- 19838538
TI  - [Academia Brasileira de Neurologia (ABN): Current Neuro newsletter in new phase].

PMID- 19838537
TI  - [Brazilian guidelines for the manegement of intracerebral hemorrhage].
AB  - Among the stroke subtypes, intracerebral hemorrhage (ICH) has the worst prognosis
      and still lacks a specific treatment. The present manuscript contains the
      Brazilian guidelines for the management of ICH. It was elaborated by the
      executive committee of the Brazilian Cerebrovascular Diseases Society and was
      based on a broad review of articles about the theme. The text aims to provide a
      rational for the management of patients with an acute ICH, with the diagnostic
      and therapeutic resources that are available in Brazil.

PMID- 19838539
TI  - Fulminant idiopathic intracranial hypertension in a pediatric patient following a
      minor head trauma.

PMID- 19838540
TI  - Flunarizine and cinnarizine-induced parkinsonism: 25 years of de Melo-Souza's
      syndrome.

PMID- 19838541
TI  - Cerebellar cryptococcoma simulating metastatic neoplasm.

PMID- 19838542
TI  - Dementia and mild cognitive impairment in Parkinson's disease.

PMID- 19838543
TI  - [Technical report].

PMID- 19838545
TI  - Combining efforts to solve Brazil's oral health problem.

PMID- 19838546
TI  - Oral health in Brazil--part I: public oral health policies.
AB  - This paper reviews the historical development of public health policies in Brazil
      and the insertion of oral health in this context. Since 1988, Brazil established
      a Unified National Health System ("Sistema Unico de Saude"--SUS), which was
      conceived to assure access to health actions and services, including oral health.
      However, a history of lack of access to health services and the health problems
      faced by the Brazilian population make the process of building and consolidating
      the SUS extremely challenging. Since 2004, the Oral Health National Policy has
      proposed a reorientation of the health care model, supported by an adaptation of
      the working system of Oral Health teams so that they include actions of health
      promotion, protection and recovery. Human resources should be prepared to act in
      this system. The qualifying process must take in consideration knowledge
      evolution, changes in the work process and changes in demographical and
      epidemiological aspects, according to a perspective of maintaining a balance
      between technique and social relevance.

PMID- 19838547
TI  - Oral health in Brazil--part II: dental specialty centers (CEOs).
AB  - The concepts of health promotion, self-care and community participation emerged
      during the 1970s and, since then, their application has grown rapidly in the
      developed world, showing evidence of effectiveness. In spite of this, a major
      part of the population in the developing countries still has no access to
      specialized dental care such as endodontic treatment, dental care for patients
      with special needs, minor oral surgery, periodontal treatment and oral diagnosis.
      This review focuses on a program of the Brazilian Federal Government named CEOs
      (Dental Specialty Centers), which is an attempt to solve the dental care deficit
      of a population that is suffering from oral diseases and whose oral health care
      needs have not been addressed by the regular programs offered by the SUS (Unified
      National Health System). Literature published from 2000 to the present day, using
      electronic searches by Medline, Scielo, Google and hand-searching was considered.
      The descriptors used were Brazil, Oral health, Health policy, Health programs,
      and Dental Specialty Centers. There are currently 640 CEOs in Brazil, distributed
      in 545 municipal districts, carrying out dental procedures with major complexity.
      Based on this data, it was possible to conclude that public actions on oral
      health must involve both preventive and curative procedures aiming to minimize
      the oral health distortions still prevailing in developing countries like Brazil.

PMID- 19838548
TI  - Reviewed evidence about the safety of the daily use of alcohol-based mouthrinses.
AB  - Current scientific knowledge provides clear evidence that alcohol-based
      mouthwashes can be beneficial in a daily oral health routine, including dental
      hygiene and plaque control. Several issues are worth discussing, in spite of the
      wealth of supporting evidence. Despite some undesirable effects to some people,
      like burning sensation, and some contraindications, like the use by infants,
      alcohol addicts and patients with mucosal injuries, there is no reason to avoid
      the use of alcohol-containing mouthwashes as long as they are used following
      proper guidance by dental professionals and the manufacturers' instructions. The
      alleged correlation between oral cancer and alcohol-based mouthrinses presents so
      little, weak, inconsistent and even contradictory evidence in the literature that
      any kind of risk warning to patients would be uncalled for. Antimicrobial
      mouthrinses are safe and effective in reducing plaque and gingivitis, and should
      be part of a comprehensive oral health care regimen that includes brushing,
      flossing and rinsing to prevent or minimize periodontal disease.

PMID- 19838549
TI  - Association between periodontal diseases and systemic diseases.
AB  - Current evidence suggests that periodontal disease may be associated with
      systemic diseases. This paper reviewed the published data about the relationship
      between periodontal disease and cardiovascular diseases, adverse pregnancy
      outcomes, diabetes and respiratory diseases, focusing on studies conducted in the
      Brazilian population. Only a few studies were found in the literature focusing on
      Brazilians (3 concerning cardiovascular disease, 7 about pregnancy outcomes, 9
      about diabetes and one regarding pneumonia). Although the majority of them
      observed an association between periodontitis and systemic conditions, a causal
      relationship still needs to be demonstrated. Further studies, particularly
      interventional well-designed investigations, with larger sample sizes, need to be
      conducted in Brazilian populations.

PMID- 19838550
TI  - Halitosis: a review of associated factors and therapeutic approach.
AB  - Halitosis or bad breath is an oral health condition characterized by unpleasant
      odors emanating consistently from the oral cavity. The origin of halitosis may be
      related both to systemic and oral conditions, but a large percentage of cases,
      about 85%, are generally related to an oral cause. Causes include certain foods,
      poor oral health care, improper cleaning of dentures, dry mouth, tobacco products
      and medical conditions. Oral causes are related to deep carious lesions,
      periodontal disease, oral infections, peri-implant disease, pericoronitis,
      mucosal ulcerations, impacted food or debris and, mainly, tongue coating. Thus,
      the aim of the present review was to describe the etiological factors, prevalence
      data and the therapeutic mechanical and chemical approaches related to halitosis.
      In general, halitosis most often results from the microbial degradation of oral
      organic substrates including volatile sulfur compounds (VSC). So far, there are
      few studies evaluating the prevalence of oral malodor in the world population.
      These studies reported rates ranging from 22% to more than 50%. The mechanical
      and chemical treatment of halitosis has been addressed by several studies in the
      past four decades. Many authors agree that the solution of halitosis problems
      must include the reduction of the intraoral bacterial load and/or the conversion
      of VSC to nonvolatile substrates. This could be achieved by therapy procedures
      that reduce the amount of microorganisms and substrates, especially on the
      tongue.

PMID- 19838552
TI  - Over-the-counter preventive and therapeutic oral products.

PMID- 19838553
TI  - Oral health policies in Brazil.
AB  - Since Oral Health policies in Brazil have been constructed according to
      circumstances and possibilities, they should be understood within a given
      context. The present analysis contextualizes several issues of the Brazilian Oral
      Health Policy, called "Smiling Brazil", and describes its present stage of
      development. Today it involves re-organizing basic oral health care by deploying
      Oral Health Teams within the Family Health strategy, setting up Centers of Dental
      Specialists within an Oral Health network as a secondary care measure, setting up
      Regional Laboratories of Dental Prosthesis and a more extensive fluoridation of
      the public water supply.

PMID- 19838554
TI  - The history and global market of oral home-care products.
AB  - This literature review reports the history and the current market of oral home
      care products. It provides information extending from the products used by our
      ancestors to those currently available, as well as on the changes in the supply
      and consumption of these products. Although the scientific knowledge about oral
      diseases has improved greatly in recent years, our ancestors had already been
      concerned with cleaning their teeth. A variety of rudimentary products and
      devices were used since before recorded history, like chewing sticks, tree twigs,
      bird feathers, animal bones, tooth powder and home-made mouth rinses. Today, due
      to technological improvements of the cosmetic industry and market competition,
      home-use oral care products available in the marketplace offer a great variety of
      options. An increase in the consumption of oral care products has been observed
      in the last decades. Estimates show that Latin America observed a 12% increase in
      hygiene and beauty products sales between 2002 and 2003, whereas the observed
      global rate was approximately 2%. A significant increase in the per capita
      consumption of toothpaste, toothbrush, mouthrinse and dental floss has been
      estimated from 1992 to 2002, respectively at rates of 38.3%, 138.3%, 618.8% and
      177.2%. Pertaining to this increased supply and consumption of oral care
      products, some related questions remain unanswered, like the occurrence of
      changes in disease behavior due to the use of new compounds, their actual
      efficacy and correct indications, and the extent of the benefits to oral health
      derived from consuming more products.

PMID- 19838555
TI  - Enamel remineralization: controlling the caries disease or treating early caries
      lesions?
AB  - The emphasis currently given to new technologies for enamel remineralization
      suggests that the changes in the understanding of the dental caries disease,
      which occurred in the last century, were either not yet adopted or were
      forgotten. Just like in the past, when the disease was "treated" by restoring
      cavities, there is presently a misunderstanding on the concept of incipient
      lesion remineralization. The aim of this paper was to review some concepts about
      caries, the natural phenomenon of enamel remineralization and the effect of
      fluoride (F) on it, and also to discuss the clinical relevance of remineralizing
      products recently launched in the marketplace aiming to "treat early caries
      lesions".

PMID- 19838556
TI  - The cariogenic dental biofilm: good, bad or just something to control?
AB  - This paper discusses the role of dental biofilm and adjunctive therapies in the
      management of dental caries. Dental biofilm is a site of bacterial proliferation
      and growth, in addition to being a location of acid production. It also serves as
      a reservoir for calcium exchange between the tooth and saliva. The salivary
      pellicle, a protein-rich biofilm layer, regulates the reaction between tooth
      surface, saliva and erosive acids. The protective effects of this pellicle on
      enamel are well established. However, understanding the effects of the
      pellicle/biofilm interaction in protecting dentin from erosive conditions
      requires further research. Saliva interacts with the biofilm, and is important in
      reducing the cariogenic effects of dental plaque as acidogenic bacteria consume
      fermentable carbohydrates producing acids that may result in tooth
      demineralization. Adequate supplies of healthy saliva can provide ingredients for
      successful remineralization. Strategies for managing the cariogenic biofilm are
      discussed with emphasis on the effectiveness of over-the-counter (OTC) products.
      However, since many toothpaste components have been altered recently, new
      clinical trials may be required for true validation of product effectiveness. A
      new generation of calcium-based remineralizing technologies may offer the ability
      to reverse the effects of demineralization. Nevertheless, remineralization is a
      microscopic subsurface phenomenon, and it will not macroscopically replace tooth
      structure lost in a cavitated lesion. Optimal management of cavitations requires
      early detection. This, coupled with advances in adhesive restorative materials
      and microsurgical technique, will allow the tooth to be restored with minimal
      destruction to nearby healthy tissue.

PMID- 19838557
TI  - Antimicrobial agents used in the control of periodontal biofilms: effective
      adjuncts to mechanical plaque control?
AB  - The control of biofilm accumulation on teeth has been the cornerstone of
      periodontal disease prevention for decades. However, the widespread prevalence of
      gingivitis suggests the inefficiency of self-performed mechanical plaque control
      in preventing gingival inflammation. This is particularly relevant in light of
      recent evidence suggesting that long standing gingivitis increases the risk of
      loss of attachment and that prevention of gingival inflammation might reduce the
      prevalence of mild to moderate periodontitis. Several antimicrobials have been
      tested as adjuncts to mechanical plaque control in order to improve the results
      obtained with oral home care. Recent studies, including meta-analyses, have
      indicated that home care products containing chemical antimicrobials can provide
      gingivitis reduction beyond what can be accomplished with brushing and flossing.
      Particularly, formulations containing chlorhexidine, mouthrinses containing
      essential oils and triclosan/copolymer dentifrices have well documented clinical
      antiplaque and antigingivitis effects. In vivo microbiological tests have
      demonstrated the ability of these antimicrobial agents to penetrate the biofilm
      mass and to kill bacteria growing within biofilms. In addition, chemical
      antimicrobials can reach difficult-to-clean areas such as interproximal surfaces
      and can also impact the growth of biofilms on soft tissue. These agents have a
      positive track record of safety and their use does not seem to increase the
      levels of resistant species. Further, no study has been able to establish a
      correlation between mouthrinses containing alcohol and oral cancer. In summary,
      the adjunct use of chemical plaque control should be recommended to subjects with
      well documented difficulties in achieving proper biofilm control using only
      mechanical means.

PMID- 19838558
TI  - Control of erosive tooth wear: possibilities and rationale.
AB  - Dental erosion is a type of wear caused by non bacterial acids or chelation.
      There is evidence of a significant increase in the prevalence of dental wear in
      the deciduous and permanent teeth as a consequence of the frequent intake of
      acidic foods and drinks, or due to gastric acid which may reach the oral cavity
      following reflux or vomiting episodes. The presence of acids is a prerequisite
      for dental erosion, but the erosive wear is complex and depends on the
      interaction of biological, chemical and behavioral factors. Even though erosion
      may be defined or described as an isolated process, in clinical situations other
      wear phenomena are expected to occur concomitantly, such as abrasive wear (which
      occurs, e.g, due to tooth brushing or mastication). In order to control dental
      loss due to erosive wear it is crucial to take into account its multifactorial
      nature, which predisposes some individuals to the condition.

PMID- 19838559
TI  - Dentine hypersensitivity: analysis of self-care products.
AB  - Dentine hypersensitivity is a condition that is often present in individuals,
      leading them to seek dental treatment. It has been described as an acute,
      provoked pain that is not attributable to other dental problems. Its actual
      prevalence is unknown, but it is interpreted as very unpleasant by individuals.
      Several therapeutic alternatives are available to manage dentine
      hypersensitivity, involving both in-office treatment and home-use products. The
      aim of this literature review was to evaluate self-care products for managing
      dentine hypersensitivity. Among the products available, dentifrices and fluorides
      are the most studied self-care products, with positive effects. However, a high
      percentage of individuals is affected by the placebo effect. Among dentifrices,
      those containing potassium salts seem to be the most promising. Dental
      professionals need to understand the advantages and limitations of these
      therapies and use this knowledge in a positive approach that might help in
      decreasing dentine hypersensitivity among patients.

PMID- 19838560
TI  - Over-the-counter whitening agents: a concise review.
AB  - Tooth discoloration is commonly found in the dental clinic and tooth bleaching
      has been considered the preferred esthetic alternative, being more conservative,
      safe and with predictable results. Supervised home-use of 10% Carbamide Peroxide
      (CP) bleaching with custom-trays is the most common bleaching procedure dispensed
      by dentists to their patients. The good results obtained with this technique
      stimulated the flourishing of new products and techniques. Over-the-counter (OTC)
      bleaching products appeared as a low-cost alternative to bleach discolored teeth
      without dentist supervision. Different OTC products are available in
      supermarkets, drug stores or on the Internet, including rinses, paint-on brushes,
      toothpastes, chewing guns, dental floss, and whitening strips. There is lack of
      clinical evidence regarding the safety and effectiveness of these products, being
      most of the studies supported by the manufacturers'. Basically, toothpastes,
      chewing gums, and dental floss are removal agents of superficial stains. Rinses
      and paint-on brushes with low levels of hydrogen peroxide have some whitening
      effect, but without clinical relevance. Strips present similar esthetic results
      and side-effects, compared to bleaching with 10% CP using trays; however, the
      studies have financial support from the manufacturers and were based on short
      term evaluations. Legislation varies widely in different countries regarding OTC
      dental bleaching. Concerns have appeared due to the potential abusive use of
      these self-medication agents, especially in young patients, with potential
      harmful results. Dentists should be acquainted with this kind of products to be
      able to inform their patients. In conclusion, there is a need for independent
      clinical trials to provide sufficient evidence regarding the use of OTC bleaching
      products.

PMID- 19838562
TI  - [6th World Congress of fluency disorders].

PMID- 19838561
TI  - Oral health self-care products: realities and myths.

PMID- 19838563
TI  - Mandibular movement range in children.
AB  - BACKGROUND: identification of the mandibular movement range is an important
      procedure in the evaluation of the stomatognathic system. However, there are few
      studies in children that focus on normal parameters or abnormalities. AIM: to
      determine the average range of mandibular movements in Brazilian children aged 6
      to 12 years; to verify the difference between genders, in each age group, and
      between the different age groups: 6-8 years; 8.1-10 years; and 10.1-12 years.
      METHOD: participants of the study were 240 healthy children selected among
      regular students from local schools of Sao Paulo State. The maximum mandibular
      opening, lateral excursion and protrusive movements, and deviation of the medium
      line, if present, were measured using a digital caliper. Student T test, Analysis
      of variance and Tukey test were considered significant for p < 0.05. RESULTS: the
      mean values observed in the studied sample were: 44.51mm for maximum mandibular
      opening; 7.71mm for lateral excursion to the right; 7.92mm for lateral excursion
      to the left; 7.45mm for protrusive movements. No statistical difference was
      observed between genders. There was a gradual increase in the range of mandibular
      movements, with significant differences mainly between the ages of 6-8 years and
      10.1-12 years. CONCLUSION: during childhood the range of mandibular movements
      increases. Age should be considered in this analysis for a greater precision in
      the diagnosis.

PMID- 19838564
TI  - Influence of the type of transducer in profound hearing loss.
AB  - BACKGROUND: individuals with profound hearing loss may present vibrotactile
      responses when tested with supra-aural earphones due to the large skull area
      exposed to vibration in these transducers. AIM: to verify the influence of the
      type of transducer when assessing air conducted pure tone thresholds in
      individuals with profound sensorineural hearing loss. METHOD: 50 individuals,
      ranging in age from 16 to 55 years, were submitted to a clinical history
      questionnaire, meatoscopy, and pure tone and speech audiometry, using both TDH-39
      supra-aural earphones and ER-3A insert earphones. RESULTS: in both pure tone and
      speech testing, thresholds were higher when obtained using insert earphones, with
      statistical significant differences for 250Hz and 1000Hz. Considering right and
      left ear testing with the different transducers, this difference was greater for
      the right ear, with statistical significant differences only for 250 Hz.
      Regarding gender, it was observed that the difference between the transducers was
      greater in males, with statistical significant differences for 250 Hz. However,
      in the SDT (Speech Detection Threshold), the greatest difference was found in
      females. CONCLUSION: people with bilateral sensorineural profound hearing loss
      presented higher (worse) thresholds with insert earphones (ER-3A) than with supra
      aural earphones (TDH-39) for low frequencies (250Hz and 1000Hz), confirming the
      existence of vibrotactile responses with supra aural earphones.

PMID- 19838565
TI  - Critical analysis of three newborn hearing screening protocols.
AB  - BACKGROUND: having knowledge about the validity of procedures for newborn hearing
      screening (NHS) is fundamental, once the purpose of these programs is to identify
      all newborns with hearing loss at an acceptable cost. AIM: to estimate the
      specificity and the false-positive rate of NHS protocols using transient evoked
      otoacoustic emissions (TEOAE) and automated auditory brainstem response (AABR).
      METHOD: participants were 200 newborns who were submitted to a hearing screening
      test between March and July 2006. Three protocols were analyzed: protocol 1, NHS
      was carried out in two steps using TEOAE; protocol 2, NHS was carried out in two
      steps using AABR; and protocol 3, NHS was carried out in one step, using the two
      procedures - testing with TEOAE followed by a retest with AABR for all the
      newborns who did not pass the TEOAE testing. RESULTS: although there was no
      statistically significant difference when comparing the referral rates to
      audiological diagnosis obtained in protocols using TEOAE and AABR, the protocol
      using TEOAE referred four times more newborns. Protocol 3 presented the highest
      referral rate, with a statistically significant difference when compared to
      protocols 1 and 2. CONCLUSIONS: the false-positive rate and consequently
      specificity were better for the protocol using AABR, followed respectively by the
      protocol using TEOAE and using both TEOAE and AABR.

PMID- 19838566
TI  - Reading comprehension levels in scholars.
AB  - BACKGROUND: important reading performance measurements are related to how and to
      what extent a child understands a written text. AIM: to study the performance of
      primary school (Ensino Fundamental) students in reading comprehension tasks
      according to the variables grade and type of school. METHOD: 160 students from
      the 3rd to the 6th grades were screened and later evaluated based on the
      retelling and question answering about a given text. RESULTS: students of the 5th
      and 6th grades of private schools presented a better performance on issues
      related to implicit information when compared to students of public schools. The
      overall analysis of the educational level revealed, through the retelling task, a
      better performance of the 6th grade students in terms of the number of present
      macro propositions and a low performance of the 5th grade students in terms of
      the achieved comprehension level, in both types of school. When answering text
      derived questions, the 4th, 5th and 6th grade students performed better than the
      3rd grade students regarding explicit questions. When considering implicit
      questions, the 4th grade students performed better than all the other grades, in
      both types of school. These results gave evidence to the influence of the
      different texts used in each grade. CONCLUSION: the 5th and 6th grades from
      private schools were the only grades that performed better when compared to
      public schools in general, regarding answering implicit knowledge questions. All
      students achieved some level of reading comprehension.

PMID- 19838567
TI  - Intelligibility of phonological disorder assessed by three groups of judges.
AB  - BACKGROUND: intelligibility of phonological disorder. AIM: to compare the
      intelligibility of phonological disorder analyzed by three distinct groups of
      judges. METHOD: the research consisted of two samples: one sample was composed by
      30 individuals with phonological disorder (assessed individuals) and the other
      sample was composed by the judges (speech-language therapists, laypeople and
      mothers). The spontaneous speech of children (i.e. three narratives of logical
      sequences) was analyzed by the different judges according to instructions given
      for intelligibility identification. For the data analysis, the mode of 90 sets of
      narratives was performed. The Kappa Concordance Analysis was then used to
      investigate statistical significance. RESULTS: the statistical analysis indicates
      greater concordance between the judges for the end assessment possibilities (good
      and insufficient). Concordance among all judges was substantial in the
      identification of good intelligibility. Judgment of regular intelligibility was
      the most difficult. CONCLUSION: it was observed that the more unintelligible the
      speech, the more severe its classification by the groups of judges.

PMID- 19838568
TI  - Voice and speech of individuals with Parkinson s Disease during amplification,
      delay and masking situations.
AB  - BACKGROUND: individuals with Parkinson's disease present voice and speech
      alterations, especially regarding loudness and speech rate. AIM: to determine the
      immediate effect of modified auditory feedback: amplification, delay and masking
      in the voice and speech of individuals with Parkinson's disease, according to
      gender. METHOD: twenty-six subjects with Parkinson's disease (15 men and 11
      women) with ages ranging between 40 and 86 years (mean age of 69 years)
      participated in the study. The speech material consisted of the counting from
      twenty to zero, four times, in four different listening conditions: habitual,
      amplified, delayed and masked. The following parameters were selected for the
      auditory-perceptual analysis: vocal quality, loudness, pitch, overall strain
      level, speech rate and articulation. The assessment was carried out by five
      Speech-Language Pathologists specialists in voice. The following parameters were
      selected for the acoustic analysis: fundamental frequency, intensity and maximum
      phonation time. RESULTS: regarding the auditory-perceptual analysis, an
      improvement in vocal quality, increase in loudness and overall strain level was
      observed in the masking situation. On the other hand, a decrease in vocal
      quality, a decrease in loudness and overall strain level, a decrease in speech
      rate and in articulation precision was observed in the amplification and delay
      situations. In the acoustic analysis, an increase in the fundamental frequency
      and vocal intensity was observed in the masking situation and an increase of the
      maximum phonation time was observed in the delay situation. CONCLUSION: the
      masking situation presents better immediate effect in the voice and speech of
      individuals with Parkinson's disease while the amplification and delay situations
      do not produce satisfactory immediate modifications.

PMID- 19838569
TI  - Communicative strategies training effectiveness to caregivers of patients with
      dementia.
AB  - BACKGROUND: the communication decline in Alzheimer's disease (AD) may have a
      significant impact on the quality of life of demented elderly and their
      caregivers. This can be subsided by the use of communicative strategies. AIM: to
      evaluate the effectiveness of a communication strategies training program for
      caregivers of patients with moderate AD. METHOD: this study identified the use
      and effectiveness of communication strategies used by caregivers, prior to and
      after training. This was done through the analyses of a questionnaire and the
      videotaped interactions between caregivers and patients. The program was used
      with seven caregivers. RESULTS: after the program the following was observed:
      significant statistical increase in the use of the proposed strategies, according
      to the reports made by the caregivers and to the observations made by the
      examiners; absence of statistical difference in the effectiveness of these
      strategies, also according to the reports made by the caregivers and to the
      observations made by the examiners; absence of changes in the correlation between
      use and effectiveness, and report of other changes related to communication.
      CONCLUSION: the training program was effective in changing the communicative
      behavior of caregivers.

PMID- 19838570
TI  - Speech disorder screening test for children.
AB  - BACKGROUND: validation of a screening test to detect speech disorders in
      children. AIM: to present validation data of a new speech disorders screening
      test (Terdaf), developed by Brazilian researchers. METHOD: 2,027 children, of
      both genders, enrolled in the first grade of elementary public schools in Canoas
      (Brazil) during 2001 were selected by a probabilistic cluster sampling. In order
      to verify Terdaf's sensibility and specificity, 200 children were re-evaluated by
      an expert in speech disorders who had no information about the screening test
      results. RESULTS: prevalence of speech disorders in this sample was of 26.7%.
      Terdaf s sensibility was of 81.6% (95%CI 67.5 - 90.8%), specificity was of 44.4%
      (95%CI 36.0 - 53.2%). When children with speech disorders due to sociocultural
      issues were excluded from the sample with positive Terdaf results, the screening
      test specificity increased to 74.1%. CONCLUSION: the new tool for speech
      disorders screening has a quick and easy application format and can be used by
      education and health professionals. It can become an important ally in the early
      diagnosis of speech disorders as well as in the prevention of co morbidities
      associated to speech disorders. A few adjustments are necessary for the
      application of this test. These are discussed and presented in this article.

PMID- 19838571
TI  - Children with chronic non-progressive encephalopathy: hearing evaluation and
      hearing aids.
AB  - AIM: to assess the auditory abilities of children with non-progressive chronic
      encephalopathy (NPCE), independently of the presence or not of hearing loss, and
      of the etiology of the encephalopathy; to characterize the benefit of hearing
      aids in children with NPCE and hearing loss. METHOD: neurologic,
      otorhinolaryngologic and auditory assessments. Application of the Parent's
      Evaluation of Aural/Oral Performance of Children (PEACH) protocol. RESULTS: out
      of the 46 assessed children, 22 (48%) presented no hearing loss and 24 (52%)
      presented some level of sensorineural hearing loss. Regarding the encephalopathy
      etiology, most of the participants presented ischemic hypoxic encephalopathy
      followed by infectious process and kernicterus. The results also indicate that 16
      (35%) parents suspected that their child had hearing loss; out of this total, 56%
      had the hearing loss confirmed. Thirty parents (65%) did not have any hearing
      complaints about their children. For these children the auditory evaluation
      indicated that 50% presented some level of hearing loss. The PEACH protocol
      proved to be effective to assess the benefit of hearing aids. CONCLUSION: the
      results indicate that over half of participants presented hearing loss. No
      correlation was observed between etiology and complaints of hearing loss. This
      means that it is not possible to predict hearing loss based on complaints. All
      children who presented hearing loss benefited from the use of hearing aids.

PMID- 19838572
TI  - Frequency modulation (FM) system in auditory processing disorder: an evidence
      based practice?
AB  - BACKGROUND: use of frequency modulation (FM) system in auditory processing
      disorder. AIM: to verify the existence of scientific evidence confirming the
      effectiveness of personal FM systems in the treatment of central auditory
      processing disorders (APD). For this purpose a systematic review of the
      literature was made, using data found in electronic databases (Medline, Lilacs
      and Cochrane library) as well as on the internet. The articles retrieved were
      analyzed according to the CONSORT statement and then classified by their evidence
      level. CONCLUSION: the search resulted in 1,589 references out of which only 19
      met the inclusion criteria. All of the analyzed articles were classified as
      having low level of evidence (expert opinion or case studies). Strong scientific
      evidence supporting the use of personal FM systems for APD intervention was not
      found. Since such device is frequently recommended for the treatment of APD, it
      becomes essential to carry out studies with high scientific evidence that could
      safely guide clinical decision making on this subject.

PMID- 19838573
TI  - Telehealth in Speech-Language Pathology and Hearing: science and technology.
AB  - BACKGROUND: distance learning (DL) is becoming a higher education modality with a
      meaningful impact. It offers students flexibility, mobility and choices. Also it
      can reach a greater number of professionals and students in a more effective way,
      when compared to other learning modalities, without losing quality. Brazil needs
      to develop direct actions to DL in the fields of Speech-Language Pathology and
      Hearing, due to its great continental territory (8,514,215.3Km(2)) and irregular
      distribution of professionals who work in these specific fields (i.e. this
      situation emphasizes the differences in quality and availability of services
      offered throughout the country). Heterogeneity in the quality and availability of
      services is also aggravated by the absence of a national strategy for continued
      education in order to recycle health professionals. This situation causes
      important differences in the knowledge and abilities of specialists from one
      region to the next. AIM: to present Telehealth studies in the field of Speech
      Language Pathology and Hearing that were developed in the last five years.
      CONCLUSION: the analyzed data indicate that more studies are needed in this
      specific field. These studies should aim at improving the quality and access to
      services which in turn would improve prevention, diagnosis and treatment of
      communication disorders.

PMID- 19838574
TI  - Echolalia in the language development of autistic individuals: a bibliographical
      review.
AB  - BACKGROUND: echolalia is one of the most common symptoms among the language
      characteristics in Autism. AIM: to provide a detailed literature revision about
      the role of echolalia in the language development process of autistic
      individuals, and to discuss the use of this language feature in the speech
      language clinical practice. The researches show classifications and analysis
      criterions of echolalia in a discursive context. A few of the analyzed studies
      are against the use of echolalia, pointing that it has no communicative function,
      and therefore should be discouraged. On the other hand, other studies indicate
      that echolalia has a communicative value and can be used as a communicative in
      speech-language intervention. CONCLUSION: this bibliographical review raises the
      issue about the importance of evaluating the conditions in which echolalia might
      occur before considering it as having a communicative value or not.

PMID- 19838575
TI  - Electromyographic and ultrasonographic assessment of the masseter muscle in
      normal individuals: a pilot study.
AB  - BACKGROUND: recent studies have used ultrasonography with the purpose of
      measuring muscle cuts. AIM: to characterize the motor control and the morphology
      of the masseter muscle in normal individuals, verifying the compatibility between
      surface electromyography and ultrasonography. METHOD: five adult individuals,
      with no alterations of the stomatognathic system. The adopted assessment
      procedures for all participants were: 1. Surface Electromyography; 2.
      Ultrasonography. RESULTS: a high correlation was observed only when comparing
      both hemifaces in the ultrasonographic assessment (rest 0.95; biting 0.86).
      CONCLUSION: the results indicate that there is no correlation between the tested
      methods, suggesting that both methods are complementary and not mutually
      excludent.

PMID- 19838576
TI  - [Maternal age: perinatal outcomes and mode of delivery].

PMID- 19838577
TI  - [Impact of maternal age on perinatal outcomes and mode of delivery].
AB  - PURPOSE: to analyze the association of the mother's age, the perinatal outcome
      and the delivery route. METHODS: information about all the patients attended at
      the Service of Obstetrics and Gynecology of a tertiary university hospital in
      Maranhao, from July to December 2006, was analyzed. Patients have been allocated
      in three groups: adolescents (10 to 19 years old), adults (20 to 34 years old),
      and aged women (>35 years old). Variables studied were: skin color, schooling,
      marital status, family income, parity, number of appointments during pre-natal
      care, gestational age at the onset of pre-natal care, delivery route, Apgar index
      at the fifth minute and birth weight. Data were processed by the Epi-info
      program, version 3.4.1, and the association among the variables was analyzed by
      the Odds Ratio (OR) or the cross product ratio, with confidence intervals (CI) of
      95%. The significance level was 0.05. RESULTS: among 2,196 patients, 25% of
      deliveries occurred in adolescents, 69% in adults and 6% in aged women. Among the
      adolescents, there was higher risk of prematurity (OR=1.46; CI 95%=1.14-1.88),
      and low birth weight (OR=1.47; CI 95%=1.13- 1.90), higher incidence of normal
      delivery as compared to the other groups (65.2%), besides the association with
      late onset of pre-natal care (OR=1.86; CI 95%=1.43-2.43), lower number of
      appointments (OR=2.03; CI 95%=1.57-2.63), and use of abortive procedures at the
      onset of gestation (OR=2.34; CI 95%=1.38-3.98). Among aged women, there was
      strong association with diabetes mellitus (OR=9.00; CI 95%=3.18-25.19), pre
      eclampsia (OR=4.38; CI 95%=3.02-6.34), premature membrane rupture (OR=5.81; CI
      95%=3.08-10.89), besides a higher chance of presenting Apgar index lower than
      seven at the fifth minute (OR=2.90; CI 95%=1.37-6.01), and higher ratio of
      cesarean section (60.3%). CONCLUSIONS: pregnancy in adolescence is associated to
      late onset of pre-natal care and few appointments along it, use of abortive
      procedures at the onset of gestation, low schooling, no mates, low birth weight,
      prematurity, and lower incidence of cephalo pelvic disproportion and pre
      eclampsia. Among aged pregnant women, there was association with diabetes, pre
      eclampsia, premature membrane rupture, Apgar index lower than seven at the fifth
      minute and higher ratio of cesarean section.

PMID- 19838578
TI  - [Factors associated to alcohol and smoking use in pregnancy].
AB  - PURPOSE: to describe alcohol and tobacco use in adult pregnant women and
      determine its association with the obstetric outcome. METHODS: analytical
      transversal study, in which 433 adult pregnant women and their newborns have been
      included, attended at a public maternity hospital in Rio de Janeiro, from 1999 to
      2006. Information on the mother and the newborn was collected at the moment of
      delivery and during puerperium through an interview and inspection of the medical
      records. 'Use of alcohol during gestation' and 'use of cigarette during
      gestation' have been considered when detected at any gestational age and written
      down on the medical record. RESULTS: it was observed that 5.5 and 7.7% of the
      pregnant women reported cigarette and alcohol use during gestation, respectively.
      Maternal features related to tobacco use during pregnancy were marital status
      (p=0.005), age (p=0.01) and pre-natal nutritional guidance (p=0.003). Tobacco use
      during pregnancy has been strongly associated with alcohol use, 31.3% of the
      women reporting concomitant use of both substances (p<0.05). No association
      between alcohol or tobacco use during gestation and obstetric outcome
      (gestational age, newborn weight at birth and newborn medical conditions; p>0.05)
      has been detected. CONCLUSIONS: these results suggest that tobacco and alcohol
      use should be investigated during pre-natal care among all women, particularly
      single women, over 35 years old, with history of miscarriage, and with unwanted
      pregnancy. Nutritional guidance had a protective effect against tobacco use
      during gestation, and thus pregnant women should be informed as to the harmful
      effects of substance use to ensure better obstetric outcome.

PMID- 19838579
TI  - [Obesity and altered arterial structure in young women with micropolycystic ovary
      syndrome].
AB  - PURPOSE: to compare echographical cardiovascular risk factors between obese and
      non-obese patients with micropolycystic ovarian syndrome (MPOS). METHODS: in this
      transversal study, 30 obese (Body Mass Index, BMI>30 kg/m(2)) and 60 non-obese
      (BMI<30 kg/m(2)) MPOS patients, aging between 18 and 35 years old, were included.
      The following variables were measured: flow-mediated dilatation (FMD) of the
      brachial artery, thickness of the intima-media of the carotid artery (IMT),
      anthropometric data, systolic arterial pressure (SAP) and diastolic arterial
      pressure (DAP). The women had no previous medical treatment and no comorbidity
      besides MPOS and obesity. For statistical analysis, the non-paired tand Mann
      Whitney's tests were used. RESULTS: obese weighted more than non-obese patients
      (92.1+/-11.7 kg versus 61.4+/-10.7 kg, p<0.0001) and had a larger waist
      circumference (105.0+/-10.4 cm versus 78.5+/-9.8 cm, p<0.0001). The SBP of obese
      patients was higher than that of the non-obese ones (126.1+/-10.9 mmHg versus
      115.8+/-9.0 mmHg, p<0.0001) and the IMT was also bigger (0.51+/-0.07 mm versus
      0.44+/-0.09 mm, p<0.0001). There was no significant difference between the groups
      as to FMD and carotid rigidity index (beta). CONCLUSIONS: obesity in young women
      with MPOS is associated with higher blood pressure and alteration of arterial
      structure, represented by a thicker intima-media of the carotid artery.

PMID- 19838580
TI  - [Evaluation of basal FSH serum levels in infertile patients with deep ovarian
      endometriosis who underwent surgery].
AB  - PURPOSE: to evaluate the ovarian reserve of infertile patients with severe
      ovarian endrometriosis, submitted to excisional surgery of endometriomas and
      attended from February to November, 2008. METHODS: prospective study, including
      30 patients with endometriosis grades III and IV, with severe ovarian impairment,
      submitted to excisional surgery of the endometriomas, and 30 patients with
      endometriosis grades I and II, allocated as a Control Group. The ovarian reserve
      was indirectly assessed, through the basal (U/L) follicle stimulating hormone
      (FSH), between the third and fifth days of the cycle, 12 months after the
      surgery. The body mass index (BMI) was calculated according to Quetelet's formula
      [weight (kg)/height(cm(2))]. The Mann-Whitney non-parametric U test was used to
      compare the variables 'age', 'BMI' and 'basal SFH' between the groups. RESULTS:
      there was no significant difference between the groups about age and BMI.
      Concerning basal FSH, in the group of patients with severe endometriosis, the
      average value was 7.0 U/L, while in the Control Group, it was 5.6 U/L (p=0.3),
      what demonstrates that the difference between the two groups was not significant.
      CONCLUSIONS: the surgery did not affect the ovarian reserve of patients with
      severe ovarian endometriosis.

PMID- 19838581
TI  - [Postural evaluation in women with chronic pelvic pain].
AB  - OBJECTIVE: to evaluate by photogrammetry, postural changes in women with chronic
      pelvic pain. METHODS: thirty women with complaint of chronic pelvic pain and 37
      without it, in a total of 67 women, were evaluated. The evaluation was realized
      through anamnesis, fixed markers in defined anatomical sites, and frontal,
      posterior, left and right lateral photographies. Photo analysis has been done by
      the software CorelDraw, version 11.0. Quantitative values for postural analysis
      of the ankle, the knee in the saggittal plan, pelvis, lumbar lordosis, thoracic
      kyphosis, adducted/abducted scapula, shoulders, head and third finger on the
      floor test were obtained. The qualitative variables studied were the knee (varus,
      valgus or normal), the presence or not of winged scapula and leveling of
      shoulders. The Statistical Package for Social Sciences, version 16.0 was used for
      the statistical analyses. Fisher's exact test and Monte-Carlo method were used to
      compare the qualitative variables, and for the quantitative data, t or Mann
      Whitney test was used. The comparisons among continuous data, corrected for
      possible confusion variables were realized by the univariate covariance analysis.
      Significance level was established at 0.05 or 5%. RESULTS: there were significant
      differences between cases and controls for protruded head (47.5 and 52.0
      masculine, respectively; p<0.0001) and for protruded shoulders (1.9 and 1.6 cm,
      respectively; p=0.03). The other variables did not show significant differences.
      CONCLUSIONS: based on these results, attention to head and shoulder posture, to
      antalgic postures and to the emotional factor is recommended. Women with chronic
      pelvic pain should be treated, taking into consideration individual muscle
      skeletal changes, and social and emotional conditions.

PMID- 19838582
TI  - [Tactile sensibility in arm of women subjected to the axillary lymph node
      dissection for breast cancer].
AB  - PURPOSE: to identify sensitivity alteration in the intercostal brachial nerve
      pathway using an extensiometer, and to observe the measurement reproducibility of
      the apparatus. METHODS: the Semmes-Weinstein extensiometer was used to evaluate
      the sensitivity along the intercostal brachial nerve pathway. Ninety-four women
      have participated in the study, divided into two groups: a CA Group composed of
      47 women submitted to breast cancer axillary lymphadenectomy, and a comparative
      group composed of 47 women without breast cancer, who had not been submitted to
      any kind of axillary surgery. Each participant underwent anamnesis and two
      consecutive applications of the extensiometer. The Control Group responses to the
      extensiometer test were used as normality reference values. RESULTS: based on
      Control Group responses, the prevalence of sensitivity changes was 85.1% in the
      CA Group. Reproducibility of the extensiometer application was confirmed in the
      CA Group through the Kappa's test (p=0.8). CONCLUSIONS: in this studied sample,
      sensitivity alterations had high prevalence; evaluations made with the
      extensiometer were reproducible, and thus we consider the equipment reliable to
      evaluate sensitivity along the intercostal brachial nerve pathway.

PMID- 19838583
TI  - [Evaluation of the main prenatal routine exams: part 2].
AB  - A good quality prenatal assistance is essential to warrant perinatal and maternal
      health. Nowadays, due to the evolution of diagnostic methods and the change in
      illness prevalence, such as the increase in diabetes and sexually transmitted
      diseases, several propedeutic procedures are available. This introduces further
      difficulty for clinicians to select the most adequate procedures and when to
      apply them during gestation, assuring the best results for both mother and
      infant. The present review aimed at evaluating the main prenatal routine tests on
      the basis of the best scientific evidence presently available.

PMID- 19838584
TI  - [Clinical importance of vascular calcifications on mammography: should we
      valorize them].

PMID- 19838585
TI  - [Variation of weigth among users of the contraceptive with depot
      medroxyprogesterone acetate according to body mass index in a six-year follow
      up].
AB  - PURPOSE: To determine weight variation in women with different Body Mass Index
      (BMI) in use of trimestral injections of depot-medroxyprogesterone acetate
      (DMPA), and compare it to women users of a non-hormonal method. METHODS:
      Retrospective study with the chart review of 226 DMPA users and 603 controls,
      users of DIU TCu380A. Women were distributed in categories, according to their
      initial BMI, as having normal weight (<25 kg/m(2)), overweight (25 to 29,9
      kg/m(2)) and being obese (>or=30 kg/m(2)), and were followed-up for six years,
      with yearly measurements of weight and BMI. The statistic test ANOVA was used to
      measure the weight variation among the groups in each BMI category every year.
      RESULTS: The average age at the onset of the method employed was higher in the
      study group than in the controls, in all the BMI categories: 31.6+/-SD 7.1 X
      27.4+/-SD 5.5 in the normal weight category (p<0.0001); 37.3+/-SD 6.8 X 29.2+/-SD
      6.0 in the overweight category (p<0.0001); and 35.3+/-SD 6.4 X 29.7+/-SD 5.8
      among obese women (p<0.0001). DMPA users showed weight increase as compared to
      the controls in the overweight category (p=0.0082); and the weight increase along
      the observation period was also higher among the DMPA users than among the
      controls, for the normal weight (p<0.0001) and overweight (p=0.0008) categories.
      In the obese group, there was no BMI variation between the groups, nor along the
      period during which they were using the method. CONCLUSIONS: There was no change
      in weight gain among DMPA users from the obese category. Prospective studies
      should be done with metabolic tests to establish the determining factors of
      weight gain in normal and overweight women.

PMID- 19838586
TI  - [Hyperprolactinemia effects on the female mice uterus during proestrous].
AB  - PURPOSE: To evaluate the effect of hyperprolactinemia induced by metoclopramide
      on the endometrium and myometrium of female mice in the proestrus phase. METHODS:
      24 female mice were randomly divided in two groups: CtrG/control and ExpG/treated
      with metoclopramide (6.7 mg/g daily). After 50 days, the animals were sacrificed
      in the proestrus phase, and the blood was collected to determine the levels of
      estradiol, progesterone and prolactin. The uterine horns were removed, fixed in
      10% formaldehyde and processed before being included in paraffin. Slices of 4
      microm were stained by hematoxylin and eosin (H/E). In the morphological
      analysis, a Carl Zeiss light microscope, with objectives varying from 4 to 400 X
      was used for each histological slice characterization. In the morphometrical
      analysis, the superficial epithelium, the lamina propria and the myometrium
      thickness were evaluated, with the help of an image analyzer (AxionVision - Carl
      Zeiss) attached to the light microscope (Carl Zeiss). The statistical analysis
      was done by ANOVA, followed by the Wilcoxon test. P-value was considered as
      significant, when <0.05. RESULTS: Our findings have shown an increase in the
      seric levels of prolactin (295.6+/-38.0 ng/mL) and significant decrease in the
      progesterone levels (11.3+/-0.9 ng/mL) in the ExpG, as compared to the CtrG
      (45.5+/-5.2 ng/mL and 18.2+/-1.6 ng/mL, respectively; p<0.001). Concerning the
      seric level of estradiol, significant differences between the groups were not
      obtained (ExpG=119.1+/-12.3 pg/mL and CtrG=122.7+/-8.4 pg/mL; p=0.418). The
      morphological study has shown that the uterus from the ExpG presented the
      endometrium with more developed superficial epithelium and lamina propria, as
      compared to the CtrG, the same happening with the myometrium. The thickness
      morphometrical values of the luminal epithelium (8.0+/-1.1 microm) and
      endometrium (116.2+/-21.1x10(2) microm) from the CtrG were lower than the ones
      from the ExpG (10.2+/-0.8 microm and 163.2+/-23.3x10(2) microm, respectively)
      with p<0.05. Nevertheless, data obtained in the myometrium have not shown
      significant differences between the groups (CtrG=152.2+/-25.2x10(2) microm and
      ExpG=140.8+/-18.0x10(2) microm). CONCLUSIONS: Data have shown that
      hyperprolactinemia induced by metoclopramide determines endometrial proliferation
      and interferes with the ovarian function, mainly in the progesterone production.

PMID- 19838587
TI  - [Topographic modifications of the urethrovesical junction and proximal urethra
      after combined Marshall-Marchetti-Krantz and Burch surgery].
AB  - PURPOSE: To study the changes in the urethrovesical junction (UVJ) and in the
      proximal urethra (PU) caused by the Marshall-Marchetti-Krantz-Burch (MMK-B)
      combined surgery through perineal ultrasonography. METHODS: An interventional,
      longitudinal and prospective study has been conducted. Thirty-two women with
      stress urinary incontinence were submitted to perineal ultrasonography before and
      30 days after surgery to evaluate the pubo-urethral distance (PUD), the proximal
      urethra length, the UVJ horizontal distance (UVJHD) and the UVJ vertical distance
      (UVJVD), the patient being at rest, and in effort during the Valsava manoeuvre.
      Results have been expressed in mean and standard deviation. The Student's t-test
      has been used to compare pre and postoperative results whenever the variables
      fulfilled the normality test criterion; otherwise, the Wilcoxon's paired test has
      been used. RESULTS: As compared with the preoperative measures, the Marshall
      Marchetti-Krantz-Burch surgery has reduced the PUD at rest (14 mm x 4.3 mm) and
      during effort (20.8 mm x 6.4 mm); has reduced the UVJHD at rest (14 mm x 4.3 mm)
      and during effort (20.8 mm x 6.4 mm); has increased the PU length at rest (16.7
      mm x 19.7 mm) and during effort (1.6 mm x 15.4 mm); and has increased UVJVD
      during effort (-5.4 mm x 14.8 mm), but has not changed it at rest (16.2 mm x 18.7
      mm, p = 0.085). CONCLUSIONS: The Marshall-Marchetti-Krantz-Burch surgery has
      significantly reduced the urethrovesical junction vertical and horizontal
      mobility without raising the urethrovesical junction.

PMID- 19838588
TI  - [Group B streptococcus maternal and neonatal colonization in preterm rupture of
      membranes and preterm labor].
AB  - PURPOSE: To identify the prevalence and risk factors of maternal colonization by
      group B streptococcus (GBS) in pregnant women with premature labor (PL) and/or
      premature membrane rupture (PMR). METHODS: Two anal and two vaginal swabs were
      collected from 203 pregnant women with diagnosis of PL or PMR assisted at the
      practice along one year. Pregnant women with imminent labor at admission were
      excluded. One swab of each source was placed in a transfer milieu and sent for
      culture in blood-agar plates; the two remaining swabs were incubated for 24 hours
      in Todd-Hewitt milieu for further sowing in blood-agar plates. Risk factors were
      analyzed by the chi-square test, Student's t-test (p-value set at 0.05 and 95%
      confidence interval) and logistic regression. The following variables were
      analyzed: age, race, parity and mother schooling; culture results by source and
      type of culture; admission diagnosis; gestational age at admission; asymptomatic
      bacteriuria; gestational age at delivery; type of delivery; neonatal GBS
      colonization rate and immediate neonatal condition. RESULTS: Prevalence of
      maternal GBS colonization was 27.6% (56 cases). The colonization rates according
      to gestational complications were 30% for PMR, 25.2% for PL and 17.8% for PL +
      PMR. Univariate analysis has shown that the variables Caucasian race, low level
      of schooling and bacteriuria were associated with higher colonization rates.
      Multivariate analysis showed that the presence of urinary infection was the only
      variable associated with maternal colonization. The GBS detection rate was
      significantly higher with the use of a selective milieu and collection from both
      anal and vaginal sources. The neonatal colonization rate was 3.1%. Two cases of
      early sepsis by GBS occurred in the sample, with prevalence of 10.8 cases per one
      thousand live births and 50% mortality rate. CONCLUSION: The studied sample
      showed high maternal colonization rates by Streptococcus agalactiae. To increase
      GBS detection rate, it is necessary to use a selective culture milieu and to
      combine anal-rectal and vaginal cultures. There was a high incidence of early
      neonatal sepsis.

PMID- 19838589
TI  - [Risk factors for pregnancy in adolescence in a teaching maternity in Paraiba: a
      case-control study].
AB  - PURPOSE: To identify factors associated with gestation in adolescence in a State
      of the northeast of Brazil. METHODS: A case-control study in the ratio of one 10
      to 19-year-old adolescent (case) for two 20 to 35-year-old women (controls), with
      a total of 168 cases and 337 controls. The variables analyzed were: schooling,
      marital status, origin, family income per capita in Brazilian currency, paid job,
      mother's schooling, and presence of adolescent's father at home. Reproductive
      variables such as age at the first intercourse, mother's history of adolescence
      pregnancy, gynecological appointments before the pregnancy, knowledge, access and
      use of contraceptive methods were also included in the analysis. RESULTS: The
      following variables were associated with gestation in adolescence: schooling
      lower than eight years, lack of a regular mate, and maternal history of
      adolescence gestation. Also, the age at the first intercourse was significantly
      lower among the adolescents and that they had a lower rate of gynecological
      appointments. Knowledge of hormonal methods and access to contraceptive methods
      were also less frequent among the adolescents. After the multiple logistic
      regression analysis, risk factors for pregnancy at adolescence were: low
      schooling (OR=2.3; CI 95%=1.3-3.8), age at the first intercourse lower than 15
      years old (OR=3.6; CI 95%=2.2-5.7), history of maternal pregnancy at adolescence
      (OR=2.6; CI 95%=1.7-3.4). The history of previous gynecological appointments
      (OR=0.3; CI 95%=0.2-0.4) and the use of hormonal methods (OR=0.6; CI 95%=0.4-0.9)
      were protecting variables. CONCLUSIONS: The main factors associated with
      pregnancy in adolescence were: the adolescent's low schooling, maternal history
      of adolescence gestation, lack of previous gynecological appointments and lack of
      access to contraceptive methods.

PMID- 19838590
TI  - [Benign metastasizing uterine leiomyoma: case reports].
AB  - Benign metastasizing leiomyomatosis (BML) is a rare disease in which the lung is
      the most affected extra-uterine organ. The BML histology is compatible with
      benignity and similar to that found in the myometrial leiomyoma. A history of
      surgically treated uterine myomatosis is reported by most of the patients with
      metastatic disease. We report the cases of two patients with uterine
      metastasizing leiomyomatosis. In the first case, a 55-year-old patient presented
      lung nodes over 20 years after being submitted to hysterectomy due to uterine
      leiomyoma. The histological and immunohistochemical studies from the lung node
      revealed that it was an implant of benign leiomyoma. The second patient, a 65
      years-old woman, presented lung and retroperitoneal nodes 20 years after being
      submitted to a hysterectomy due to uterine leiomyoma.

PMID- 19838591
TI  - [Management of preterm labor].
AB  - The main purpose of using uterulytic in preterm delivery is to prolong gestation
      in order to allow the administration of glucocorticoid to the mother and/or to
      accomplish the mother's transference to a tertiary hospital center. Decisions on
      uterolytic use and choice require correct diagnosis of preterm delivery, as well
      as the knowledge of gestational age, maternal-fetal medical condition, and
      medicine's efficacy, side-effects and cost. All the uterolytics have side
      effects, and some of them are potentially lethal. Studies suggest that beta
      adrenergic receptor agonists, calcium blockers and cytokine receptor antagonists
      are effective to prolong gestation for at least 48 hours. Among these three
      agents, atosiban (a cytokine receptor antagonist) is safer, though it presents a
      high cost. Magnesium sulfate is not efficient to prolong gestation and presents
      significant side-effects. Cyclooxygenase inhibitors also present significant side
      effects. Up till now, there is not enough evidence to recommend the use of nitric
      oxide donors to inhibit preterm delivery. There is no basis for the use of
      antibiotics to avoid prematurity in face of preterm labor.

PMID- 19838592
TI  - Suicidal ideation among students enrolled in healthcare training programs: a
      cross-sectional study.
AB  - OBJECTIVE: We aimed to assess the presence of suicidal ideation, depressive
      symptoms and symptoms of hopelessness in three healthcare training programs.
      METHOD: The study's population comprised all students enrolled at the Medical
      School of the Fundacao do ABC, Brazil, from 2006 to 2007 compared to students
      enrolled in nursing and pharmacy programs. We applied the Beck Scale for Suicidal
      Ideation, the Beck Depression Inventory and the Beck Hopeless Scale to assess
      psychiatric symptomatology. The general response rates of the medical, nursing,
      and pharmacy students were 56%, 56% and 61%, respectively. RESULTS: There was no
      difference regarding the presence of suicidal ideation among medical, nursing and
      pharmacy students. There was also no difference regarding the presence of either
      depression or hopelessness in medical students in comparison to nursing and
      pharmacy students. In comparison to nursing and pharmacy students, significantly
      higher severity rates in terms of hopelessness were observed only among medical
      students. CONCLUSION: Although we did not observe significant differences
      regarding suicidal ideation and depression among the three healthcare programs,
      our findings suggest that the presence of suicidal ideation is indeed a source of
      concern. Early identification of these symptoms is crucial in order to offer
      appropriate support and treatment and prevent deaths by suicide.

PMID- 19838593
TI  - Using the Defensive Style Questionnaire to evaluate the impact of sex
      reassignment surgery on defensive mechanisms in transsexual patients.
AB  - OBJECTIVE: To evaluate the impact of sex reassignment surgery on the defense
      mechanisms of 32 transsexual patients at two different points in time using the
      Defensive Style Questionnaire. METHOD: The Defensive Style Questionnaire was
      applied to 32 patients upon their admission to the Gender Identity Disorder
      Program, and 12 months after they had undergone sex reassignment surgery.
      RESULTS: There were changes in two defense mechanisms: anticipation and
      idealization. However, no significant differences were observed in terms of the
      mature, neurotic and immature categories. DISCUSSION: One possible explanation
      for this result is the fact that the procedure does not resolve gender dysphoria,
      which is a core symptom in such patients. Another aspect is related to the early
      onset of the gender identity disorder, which determines a more regressive
      defensive structure in these patients. CONCLUSION: Sex reassignment surgery did
      not improve the defensive profile as measured by the Defensive Style
      Questionnaire.

PMID- 19838594
TI  - Food intake and serum levels of iron in children and adolescents with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: To investigate hematologic variables related to iron deficiency and
      food intake in attention-deficit/hyperactivity disorder. METHOD: The sample
      comprised 62 children and adolescents (6-15 years old) divided into three groups:
      Group 1: 19 (30.6%) patients with attention-deficit/hyperactivity disorder using
      methylphenidate for 3 months; Group 2: 22 (35.5%) patients with attention
      deficit/hyperactivity disorder who were methylphenidate naive and Group 3: 21
      (33.9%) patients without attention-deficit/hyperactivity disorder. Serum iron,
      ferritin, transferrin, hemoglobin, mean corpuscular volume, red cell distribution
      width, mean corpuscular hemoglobin concentration, nutritional diagnostic
      parameters - Body Mass Index Coefficient, food surveys were evaluated among the
      groups. RESULTS: The attention-deficit/hyperactivity disorder group drug naive
      for methylphenidate presented the highest red cell distribution width among the
      three groups (p = 0.03). For all other hematologic and food survey variables, no
      significant differences were found among the groups. No significant correlation
      between dimensional measures of attention-deficit/hyperactivity disorder symptoms
      and ferritin levels was found in any of the three groups. CONCLUSION: Peripheral
      markers of iron status and food intake of iron do not seem to be modified in
      children with attention-deficit/hyperactivity disorder, but further studies
      assessing brain iron levels are needed to fully understand the role of iron in
      attention-deficit/hyperactivity disorder pathophysiology.

PMID- 19838595
TI  - Wives of pathological gamblers: personality traits, depressive symptoms and
      social adjustment.
AB  - OBJECTIVE: Wives of pathological gamblers tend to endure long marriages despite
      financial and emotional burden. Difficulties in social adjustment, personality
      psychopathology, and comorbidity with psychiatric disorders are pointed as
      reasons for remaining on such overwhelming relationships. The goal was to examine
      the social adjustment, personality and negative emotionality of wives of
      pathological gamblers. METHOD: The sample consisted of 25 wives of pathological
      gamblers, mean age 40.6, SD = 9.1 from a Gambling Outpatient Unit and at GAM
      ANON, and 25 wives of non-gamblers, mean age 40.8, SD = 9.1, who answered
      advertisements placed at the Universidade de Sao Paulo hospital and medical
      school complex. They were selected in order to approximately match demographic
      characteristics of the wives of pathological gamblers. Subjects were assessed by
      the Social Adjustment Scale, Temperament and Character Inventory, Beck Depression
      Inventory and State-Trait Anxiety Inventory. RESULTS: Three variables remained in
      the final Multiple Logistic Regression model, wives of pathological gamblers
      presented greater dissatisfaction with their marital bond, and higher scores on
      Reward Dependence and Persistence temperament factors. Both, Wives of
      pathological gamblers and wives of non-gamblers presented well-structured
      character factors excluding personality disorders. CONCLUSION: This personality
      profile may explain wives of pathological gamblers emotional resilience and their
      marriage longevity. Co-dependence and other labels previously used to describe
      them may work as a double edged sword, legitimating wives of pathological
      gamblers problems, while stigmatizing them as inapt and needy.

PMID- 19838596
TI  - Phlegmasia cerulea dolens--a rare, life-threatening condition.
AB  - Phlegmasia cerulea dolens is a rare form of massive proximal venous thrombosis of
      the lower extremities associated with a high degree of morbidity, presenting with
      sudden severe lower extremity pain with edema and cyanosis. Venous gangrene,
      venous congestion with massive fluid sequestration leading to circulatory
      collapse, and shock causing death can ensue if not promptly diagnosed and
      treated. We present a clinical image of a 55-year-old man with newly diagnosed
      cholangiocarcinoma who presented with worsening left lower extremity pain. We
      found painful swelling with purple discoloration extending up to the ankle joint.
      Distal arterial pulses were palpable. Doppler ultrasound revealed extensive
      thrombosis in all segments of the deep vein bilaterally except the right iliac
      segment. Anticoagulation with heparin was initiated. The patient underwent an
      emergency left iliac thrombectomy for salvage of the limb and placement of a
      prophylactic inferior vena cava filter. The patient's symptoms resolved.

PMID- 19838597
TI  - Urinary exosomes.
AB  - Exosomes are nanovesicles of endocytic origin that are secreted into the
      extracellular space or body fluids when a multivesicular body (MVB) fuses with
      the cell membrane. Interest in exosomes intensified after their description in
      antigen-presenting cells and the observation that they can significantly moderate
      immune responses in vivo. In the past few years, several groups have reported on
      the secretion of exosomes by almost all cell types in an organism. In addition to
      a common set of membrane and cytosolic molecules, exosomes harbor unique subsets
      of proteins, reflecting their cellular source. Major research efforts were put
      into their surprisingly various biological functions and in translating knowledge
      into clinical practice. Urine provides an exciting noninvasive alternative to
      blood or tissue samples as a potential source of disease biomarkers. Urinary
      exosomes (UE) became the subject of serious studies just a few years ago. A
      recent large-scale proteomics-based study of normal UE revealed a myriad of
      proteins, including disease-related gene products. Thus, UE have valuable
      potential as a source of biomarkers for early detection of various types of
      diseases, monitoring the disease evolution and/or response to therapy. As a
      relatively new field of research, it still faces many challenges, but UE have
      already shown some straightforward potential.

PMID- 19838598
TI  - Posterior urethral valves.
AB  - The most common cause of lower urinary tract obstruction in male infants is
      posterior urethral valves. Although the incidence has remained stable, the
      neonatal mortality for this disorder has improved due to early diagnosis and
      intensive neonatal care, thanks in part to the widespread use of prenatal
      ultrasound evaluations. In fact, the most common reason for the diagnosis of
      posterior urethral valves presently is the evaluation of infants for prenatal
      hydronephrosis. Since these children are often diagnosed early, the urethral
      obstruction can be alleviated rapidly through catheter insertion and eventual
      surgery, and their metabolic derangements can be normalized without delay,
      avoiding preventable infant mortality. Of the children that survive, however,
      early diagnosis has not had much effect on their long-term prognosis, as 30%
      still develop renal insufficiency before adolescence. A better understanding of
      the exact cause of the congenital obstruction of the male posterior urethra,
      prevention of postnatal bladder and renal injury, and the development of safe
      methods to treat urethral obstruction prenatally (and thereby avoiding the
      bladder and renal damage due to obstructive uropathy) are the goals for the care
      of children with posterior urethral valves[1].

PMID- 19838599
TI  - The podocyte in diabetic kidney disease.
AB  - Approaching epidemic levels, diabetic kidney disease (DKD) is now the leading
      cause of end-stage renal disease (ESRD). Microalbuminuria is an early clinical
      marker of DKD that results from damage to the glomerular filtration barrier at
      the level of the highly differentiated glomerular podocyte cells. Injury to these
      epithelial cells, podocytopathies, includes cellular hypertrophy, foot process
      effacement, detachment from the glomerular basement membrane, and apoptosis. Here
      we review the role of a number of recently identified factors that contribute to
      podocytopathies in DKD. These factors include members of the renin-angiotensin
      system (RAS), including angiotensin-converting enzyme (ACE) types 1 and 2,
      prorenin and its receptor, reactive oxygen species (ROS), prostanoids, peroxisome
      proliferator-activated receptors (PPAR), advanced glycation end-products (AGEs)
      and their receptors (RAGE), adiponectin, and microRNAs. As the number of
      therapeutic options that slow, but do not halt, the progression of DKD to ESRD
      remains limited, a more comprehensive understanding of the signaling events that
      contribute to this increasingly prevalent disease may identify novel avenues for
      treatment and prevention.

PMID- 19838600
TI  - Determination of toxic metals in Indian smokeless tobacco products.
AB  - This study targets the lesser-known ingredients of smokeless tobacco products,
      i.e., the toxic metals, in Indian brands. The metals selected in the study
      included lead (Pb), cadmium (Cd), arsenic (As), copper (Cu), mercury (Hg), and
      selenium (Se). The differential pulse anodic stripping voltammetry (DPASV)
      technique was used for estimating the metals Pb, Cd, and Cu; square wave
      voltammetry for As; and the cold vapor atomic absorption technique for Hg. The
      resulting levels of the metals were compared to the daily consumption of the
      smokeless tobacco products. It was observed that almost 30% of gutkha brand
      samples exceeded the permissible levels of metals Pb and Cu, when compared to the
      provisional tolerable intake limits determined by the FAO/WHO. The reliability of
      data was assured by analyzing standard reference materials.

PMID- 19838601
TI  - Comparison of quantitative structure-activity relationship model performances on
      carboquinone derivatives.
AB  - Quantitative structure-activity relationship (qSAR) models are used to understand
      how the structure and activity of chemical compounds relate. In the present
      study, 37 carboquinone derivatives were evaluated and two different qSAR models
      were developed using members of the Molecular Descriptors Family (MDF) and the
      Molecular Descriptors Family on Vertices (MDFV). The usual parameters of
      regression models and the following estimators were defined and calculated in
      order to analyze the validity and to compare the models: Akaike's information
      criteria (three parameters), Schwarz (or Bayesian) information criterion, Amemiya
      prediction criterion, Hannan-Quinn criterion, Kubinyi function, Steiger's Z test,
      and Akaike's weights. The MDF and MDFV models proved to have the same estimation
      ability of the goodness-of-fit according to Steiger's Z test. The MDFV model
      proved to be the best model for the considered carboquinone derivatives according
      to the defined information and prediction criteria, Kubinyi function, and
      Akaike's weights.

PMID- 19838602
TI  - Dental tissue--new source for stem cells.
AB  - Stem cells have been isolated from many tissues and organs, including dental
      tissue. Five types of dental stem cells have been established: dental pulp stem
      cells, stem cells from exfoliated deciduous teeth, stem cells from apical
      papilla, periodontal ligament stem cells, and dental follicle progenitor cells.
      The main characteristics of dental stem cells are their potential for
      multilineage differentiation and self-renewal capacity. Dental stem cells can
      differentiate into odontoblasts, adipocytes, neuronal-like cells, glial cells,
      osteoblasts, chondrocytes, melanocytes, myotubes, and endothelial cells. Possible
      application of these cells in various fields of medicine makes them good
      candidates for future research as a new, powerful tool for therapy. Although the
      possible use of these cells in therapeutic purposes and tooth tissue engineering
      is still in the beginning stages, the results are promising. The efforts made in
      the research of dental stem cells have clarified many mechanisms underlying the
      biological processes in which these cells are involved. This review will focus on
      the new findings in the field of dental stem cell research and on their potential
      use in the therapy of various disorders.

PMID- 19838603
TI  - The effect of sex peptide and calorie intake on fecundity in female Drosophila
      melanogaster.
AB  - The accessory gland proteins (Acps) of the male Drosophila cause changes in the
      behavior and physiology of female flies. Sex peptide (SP) is one of the Acps that
      initiates many changes, including an increase in egg production. The data
      presented here show that SP overexpression in transgenic (G-10) female flies
      increases egg production when females are kept on a standard and high-calorie
      diet, relative to controls that do not express SP. Particularly, a high increase
      in egg production observed in G-10 females on a high-calorie diet suggests that
      SP overexpression magnifies the female response to caloric uptake. However, on a
      calorie-restricted diet, the fecundity of G-10 females overexpressing SP is lower
      than control females. On a high-calorie diet, mating increases early egg
      production in G-10 and control females, but lifelong total egg production is only
      increased in control females, most likely due to the physiological changes set
      off by substantial initial egg production in G-10 females.

PMID- 19838604
TI  - Effect of different surface treatments on the shear and flexural re-bond
      strengths of a micro-hybrid composite.
AB  - AIM: This study compared the shear bond strength (SBS) and flexural strength (FS)
      of repaired interfaces using three techniques of surface preparation and repair
      of a micro-hybrid composite. METHODS AND MATERIALS: Composite specimens for SBS
      tests (n=36: diameter=8 mm, thickness=3 mm) for repair were shaped in a metal
      mold, visible-light cured, and embedded in dental stone. Composite specimens for
      FS tests (n=36: 2 mm x 2 mm x 12.5 mm) for repair were shaped in a silicone mold.
      Three different methods of surface preparation were evaluated: Group A (control)
      specimens were treated by etching with 35% phosphoric acid; Group B specimens
      were air-abraded with 50 microm aluminum oxide at 100 psi; and Group C specimens
      received two parallel, 1 mm-deep grooves using a (1/4)-round bur before being
      treated by etching with 35% phosphoric acid. After surface treatment, a bonding
      agent was placed on each specimen, which was then light cured. Repairs were
      accomplished by adding more composite to the SBS or FS specimens. Specimens were
      thermocycled 500 times between 5 degrees C and 55 degrees C with 30-second dwell
      times. All specimens were tested by loading to failure at a rate of 0.5 mm/min
      using an Instron Universal Testing Machine. RESULTS: Mean SBSs in MPa were: Group
      A=24.5 +4.4, Group B=28.5 +4.3, and Group C=27.0 +2.8. Mean FSs (MPa) were: Group
      A=60.5 +9.9, Group B=73.9 +13.2 and Group C=81.3 +14.3. For the FS tests, Group B
      and C were significantly different than Group A, but Group C was not
      significantly different than group B. For the SBS test, Group B was significantly
      different than Group A, but Group C was not significantly different. CONCLUSION:
      Acid-etching alone was not very effective in producing well-bonded composite
      repairs (only 55% of the FS of normal micro-hybrid composite). Mechanical
      retention was more effective (SBS, FS) than acid-etching and as effective (SBS)
      or more effective (FS) than air-abrasion (p<0.05) for repaired composite
      specimens. CLINICAL SIGNIFICANCE: Either mechanical retention or air abrasion is
      recommended prior to repairing an existing composite restoration to achieve the
      highest bond strength.

PMID- 19838605
TI  - The effect of various placement techniques on the microhardness of Class II
      (slot) resin composite restorations.
AB  - AIM: To analyze the influence of various placement techniques on Vickers
      microhardness of Class II cavities restored using resin composite in different
      depths and layers. METHODS AND MATERIALS: Sixty-four standardized Class II
      cavities (5.0 x 3.0 x 1.5 mm3) were prepared in sound human, maxillary premolars.
      The cavities were divided into four experimental groups (n=16) according to the
      composite placement technique used: incremental technique using a Palodent matrix
      (IP), incremental technique using a transparent matrix (IT), centripetal
      technique using a Palodent matrix (CP), and the centripetal technique using a
      transparent matrix (CT). The cavities were restored with Single Bond, Z100
      composite resin system. After 24 hours of storage in envelopes in an amber
      colored box, the restorations were finished, polished, and kept for one week
      before conducting a hardness test. The microhardness test was carried out using a
      0.5 kg load for 20 seconds at different depths and layers of proximal surfaces.
      Statistical analysis was done using a t-test, ANOVA, and a Tukey's test
      (alpha=0.05). RESULTS: In contrast, the matrix bands, the methods of composite
      insertion, had a significant effect on hardness. The greatest surface hardness of
      resin composite was related to the use of the centripetal technique and a
      transparent matrix (p<0.05). With regard to cavity depths, the hardness at the
      top surface was significantly greater, followed by the middle and bottom cavity
      depths. A greater hardness was obtained in the mesial-distal direction within the
      external layer compared with the middle and internal layers using the centripetal
      method (p<0.05). CONCLUSION: The kind of matrix and filling technique could have
      a significant effect on surface microhardness. The top surface had the greatest
      hardness in comparison to different depths. In the centripetal technique, the
      external layer of the proximal wall had greater hardness than the other layers.
      CLINICAL SIGNIFICANCE: While the microhardness of all of the experimental
      placement techniques in the different depths and layers was within a clinically
      acceptable range, the greatest hardness was obtained using the centripetal
      technique with a transparent matrix, making it the technique of choice.

PMID- 19838606
TI  - A comparison of acrylic and multilithic teeth bond strengths to acrylic denture
      base material.
AB  - AIM: Debonding of denture teeth from the denture base can be frustrating for both
      the clinician as well as his or her patients. The wear resistance of composite
      denture teeth has been well investigated since their introduction, but there have
      been few studies about the bonding of these teeth to acrylic denture base resins.
      The aim of this study was to compare the bond strengths of two brands of acrylic
      and one brand of multilithic denture teeth to acrylic denture base material.
      METHODS AND MATERIALS: In this experimental-laboratory study, three types of
      denture teeth--Yaghoot, Super Brilian, and Major--were used. After grinding the
      glossy ridge lap surfaces, the teeth were mounted on two sides of triangular
      shaped wax models. Then the wax elimination and resin processing laboratory
      procedures were carried out as is done with the fabrication of a complete
      denture. Each of the specimens was tested using a universal testing machine with
      a cross head speed of 5 mm/min at an angle of 130 degrees to the long axis of the
      teeth. The data were analyzed using one-way ANOVA and Chi-square tests. RESULTS:
      The mean bond strength in the Yaghoot group was 717.43+/-293.59 N while in the
      Super Brilian group it was 578.40+/-395.38 and in the Major group, 547.95+/
      296.75N. However, there was no significant difference between the three groups
      (p=0.194). CONCLUSION: Although the mean bond strength in the multilithic group
      was higher than in the other groups, no significant difference was found between
      the three groups. There was no significant difference between the three groups
      with regard to the prevalence and type of fracture site. CLINICAL SIGNIFICANCE:
      The bonding strength of multilithic denture teeth to denture base resins was
      found to be comparable to, and even slightly higher than, acrylic conventional
      denture teeth, making them a promising choice for clinicians in the fabrication
      of removable dentures.

PMID- 19838607
TI  - Dental treatment duration as an indicator of the behavior of 3-to 9-year-old
      pediatric patients in clinical dental settings.
AB  - AIM: The aim of this study was to evaluate the age-specific effect of treatment
      duration on pediatric patient behavior. METHODS AND MATERIALS: A total of 450
      children 3 to 9 years of age were allocated into six consecutive age groups (n=75
      for each group). All children received dental treatment procedures which included
      the fabrication of a Type 1 composite resin restoration, then a dental
      prophylaxis followed by fluoride therapy with each procedure requiring an average
      of 20 minutes. The children's behavior was evaluated at the end of each treatment
      period using the sound, eye, and motor (SEM) scale. RESULTS: The results of a
      mixed analysis of variance (ANOVA) indicated a significant main effect of
      treatment duration, F (1.69, 255.01) = 188.29, P < 0.001, and of chronological
      age, F (1, 144) = 115.82, P < 0.001. Moreover, the main effects of time and
      chronological age was qualified by a significant interaction between time and
      chronological age, F (8.86, 255.01) = 115.82, P < 0.001. The beta weights (0.64
      for age versus 0.44 for time) suggest chronological age contributes the most to
      predicting the behavior of children during dental treatment followed by the
      duration of treatment. CONCLUSION: Treatment duration may affect the behavior of
      pediatric patients parallel with chronological age and, thus, should be
      considered in the arrangement of the treatment plan. CLINICAL SIGNIFICANCE: The
      findings of this study suggest appropriate pediatric behavior management should
      include thoughtful scheduling of appointments according to a treatment plan
      formulated with consideration of the effects of age and appointment length.

PMID- 19838608
TI  - Oral squamous cell carcinoma: a clinicopathological study of 342 Thai cases.
AB  - AIM: To conduct a clinicopathological review of oral squamous cell carcinoma
      (SCC) and to analyze it with respect to gender, age at diagnosis, clinical
      presentation, lesion location, and histological grading. METHODS AND MATERIALS:
      Information on the clinicopathological characteristics of SCC was obtained from
      pathology reports of 342 cases. RESULTS: The male to female ratio was 1:1 and the
      incidence increased with age. Among the patients 4.7% were younger than 40 years
      and males were predominant in this subgroup. The alveolar ridge and gingiva were
      the most commonly affected sites (50%). The majority of the SCC cases presented
      as ulcers or masses. Swelling and/or pain were the first signs and/or symptoms in
      most patients (52.6%). The age at diagnosis in relation to the site of occurrence
      varied. Conventional SCC was the most common subtype (88%). Well-differentiated
      SCC was the most common histological grading (78.6%). CONCLUSION: In the present
      study, the incidence of SCC was age-related and showed equal gender distribution.
      CLINICAL SIGNIFICANCE: Routine examination of the oral cavity by dental
      practitioners and other health care providers aids in the early detection of
      premalignant and malignant oral disease. Dentists can play a significant role in
      disseminating information regarding oral cancer.

PMID- 19838609
TI  - The prevalence of occlusal disharmony and its associated causes in complete
      dentures.
AB  - AIM: Occlusal disharmony is frequently observed among edentulous patients. With
      the side effects of occlusal disharmony in mind, the goal of this research was to
      investigate the prevalence of occlusal disharmony in inserted complete dentures
      and its associated causes. METHODS AND MATERIALS: This cross-sectional study was
      conducted on 107 selected patients. Factors such as age, gender, ridge
      relationship on the articulator, occlusal scheme, and the performance of a
      clinical remount from patients' treatment records were investigated. The presence
      and/or status of any occlusal disharmony was determined by a calibrated
      prosthodontist extraorally and qualitatively. Occlusal disharmony is defined as
      the absence of simultaneous bilateral contacts between the opposing posterior
      teeth in centric relation. The prevalence of occlusal disharmony was determined
      and the roles of the aforementioned factors were studied and analyzed using a Chi
      square analysis. The results were considered significant at p<0.05. RESULTS: Out
      of 107 patients, 31 patients (28.8%) showed occlusal disharmony. No statistically
      significant relationship was found between occlusal disharmony and age, gender,
      ridge relationships, or occlusal scheme (p<0.5). Twenty-five (81%) out of 31
      complete dentures with occlusal disharmony were not clinically remounted. There
      was a highly significant relationship between the absence of clinical remounting
      and occlusal disharmony (p<0.001). CONCLUSION: Within the limits of this study,
      the prevalence of occlusal disharmony was noticeable. A randomized clinical trial
      is strongly recommended to investigate factors related to the incidence of
      occlusal disharmony. CLINICAL SIGNIFICANCE: It is important to refine the
      occlusion of a complete denture after laboratory processing of the denture before
      it is delivered to the patient.

PMID- 19838610
TI  - The clinical outcomes of 234 spiral family implants.
AB  - AIM: Spiral family implants (SFIs) are a new type of implant fixture with a
      conical internal helix and a variable thread design. The aim of this
      retrospective study was to evaluate the clinical outcomes of a series of SFIs.
      METHODS AND MATERIALS: A total of 234 SFIs were placed in 86 patients (55 females
      and 31 males, median age 53 years) during the period between May 2004 and
      November 2007. The mean follow-up was 13 months. Several host, surgery, and
      implant-related factors were investigated, and the Kaplan Meier algorithm and the
      Cox regression were used to detect variables associated with the clinical
      outcome. RESULTS: Only nine out of 234 implants were lost (i.e., survival rate
      (SVR) of 96.2%) and no differences were detected among the studied variables.
      CONCLUSION: SFIs have a high SVR similar to those reported in previous studies on
      different implant types. CLINICAL SIGNIFICANCE: SFIs demonstrated a very high
      primary stability which offers the potential for use of a specific implant device
      for immediate loading. However, additional studies are necessary to verify their
      outcome on the medium/long period.

PMID- 19838611
TI  - Causes and patterns of loss of permanent teeth among patients attending a dental
      teaching institution in south India.
AB  - AIM: The aims of the present study are to determine the causes and pattern of
      loss of permanent teeth among patients attending a dental teaching institution in
      southern India. METHODS AND MATERIALS: Data collected from patients attending the
      outpatient wing of the Sri Sankara Dental College, Kerala, during a three month
      period was used for the study. The cause for extraction was classified as
      follows: (1) caries and its sequelae, (2) periodontal disease, (3) orthodontic
      purposes, (4) impactions, (5) prosthodontic purposes, and (6) other reasons.
      RESULTS: A total of 1791 permanent teeth were extracted of which 708 (39.5%)
      teeth were extracted due to caries and its sequelae, 508 (28.4%) due to
      periodontal disease, 347 (19.4%) for orthodontic purposes, 29 (1.6%) due to
      impactions, 155 (8.7%) for prosthodontic purposes, and 44 (2.5%) for other
      reasons. CONCLUSION: The results of the present study suggest caries and
      periodontal disease are the major causes of tooth mortality in the study
      population. CLINICAL SIGNIFICANCE: Data regarding the causes of tooth loss
      indirectly provides invaluable information on the pattern of oral health in a
      population which can be utilized for planning public health policies designed to
      address the burden of oral diseases.

PMID- 19838612
TI  - Histologic evaluation of the effects of Er:YAG laser on bone ablation.
AB  - AIM: The aim of the present study was to compare the healing of bone defects
      created using an Er:YAG laser with those defects created using a surgical bone
      drill. METHODS AND MATERIALS: Fourteen Wistar rats were used for this study.
      Femurs were perforated with a surgical bone drill, coupled to a micromotor (bur
      group) to create a bone defect. Another defect was created using a 2940 nm
      wavelength Er:YAG laser on the same femur (Er:YAG Group). The Er:YAG laser was
      used with a energy density of 1.5 W in noncontact mode under a water coolant.
      Incisions were then sutured with polyglycolic acid sutures. Seven rats were
      sacrificed at day ten and the other seven at day 20 to compare the status of bone
      repair of each group at those post-surgical intervals. The femurs were fixed with
      10% neutral buffered formalin and decalcified in 10% EDTA. The specimens were
      embedded in paraffin and sectioned at a 5 micron thickness and stained with
      hematoxylin and eosin (H&E) stain. The specimens were examined at a magnification
      of X100 and scored using a standardized histologic scoring system. RESULTS:
      Stages of bone healing including union, spongioza, cortex, and bone marrow
      development were evaluated and no significant difference between groups were
      found at days ten and 20 of healing. There was also no significant difference
      among the two groups in sum of histologic scores on day ten. CONCLUSION: Bone can
      be ablated effectively and precisely using a Er:YAG laser without the vibration
      associated with steel surgical burs, but it is a slower process than when burs
      are used. There was no significant difference between the two groups in terms of
      bone repair at ten and 20 day intervals of healing. CLINICAL SIGNIFICANCE: Within
      the limits of this study a 2940 nm Er:YAG laser at 1.5 W can be used with
      confidence in cases requiring effective bone ablation.

PMID- 19838613
TI  - Immediate implant placement and provisional crown fabrication after a minimally
      invasive extraction of a peg-shaped maxillary lateral incisor: a clinical report.
AB  - AIM: The aim of this case report is to describe the replacement of a maxillary
      peg-shaped lateral incisor with the placement of an immediate implant and a
      provisional restoration following a minimally invasive extraction to preserve
      anterior esthetics. BACKGROUND: Extraction sites in the anterior maxilla can
      present restorative challenges with regard to esthetics. Resistance to wearing a
      temporary removable partial denture during healing makes immediate implant
      therapy an appealing alternative to patients. Implant placement into fresh
      extraction sockets using no flap elevation has recently become more popular due
      to some advantages including less bleeding, swelling, and the preservation of
      existing soft tissue contours. CASE REPORT: A 20-year-old woman with a peg-shaped
      maxillary left lateral incisor was treated using an implant placed into the fresh
      extraction socket using a flapless approach and immediate provisional crown
      fabrication. Flapless implant placement helps to preserve site morphology by
      protecting and supporting existing hard and soft tissues while minimizing
      surgical trauma to the adjacent tissues. Using a previously fabricated acrylic
      index, a provisional acrylic crown was fabricated on the adjusted temporary
      abutment and delivered to the patient the same day during the extraction visit.
      SUMMARY: This report describes the diagnosis and treatment of an over-prepared
      peg-shaped maxillary left lateral incisor associated with multiple crown
      decementations. The tooth was extracted without flap elevation and an implant was
      inserted immediately using flapless surgery and placement of an immediate
      provisional single crown. CLINICAL SIGNIFICANCE: Flapless implant insertion into
      fresh extraction sockets and placement of immediate provisional crowns in cases
      involving the maxillary anterior region represent a viable treatment option in
      appropriate clinical situations where esthetics are a high priority. The strategy
      preserves optimum gingival contours and papillary height may be a viable option
      compared to fixed partial dentures.

PMID- 19838614
TI  - Management of a Type III dens invaginatus using a combination surgical and non
      surgical endodontic therapy: a case report.
AB  - AIM: The aim of this report is to present a case of Type III dens invaginatus in
      a maxillary lateral incisor with a periapical lesion and its successful treatment
      using a combination of surgical and non-surgical therapy. BACKGROUND: The
      morphology of the root canal system is unique for individual teeth. A precise
      understanding of the morphology is very important for a successful root canal
      treatment. Dens invaginatus is a rare dental anomaly that can give rise to many
      complex anatomical forms. The complete removal of the diseased pulp tissue can be
      a challenge for clinicians due to the complexity of internal canal anatomy and
      may require either non-surgical endodontic therapy alone or that therapy may have
      to be combined with surgical endodontics to achieve an adequate sealing of the
      root canal system. CASE REPORT: A 22-year-old male presented for evaluation of a
      recurrent painless sinus tract in the attached gingiva adjacent to the maxillary
      right lateral incisor. The tooth responded negatively to vitality tests while the
      right central incisor responded normally. Clinically an anatomical malformation
      in the crown was detected in the form of an abnormal bulbous contour of the tooth
      in the palatal region above the cingulum. Radiograph evaluation confirmed the
      presence of dens invaginatus and a periapical radiolucent lesion. The patient
      received combined non-surgical and surgical endodontic therapy to achieve a
      favorable outcome. SUMMARY: Complications presented by Type III dens invaginatus
      and acute periapical abscess necessitated the use of combined non-surgical and
      surgical endodontic therapy to attain a favorable seal of the root canal. The
      prognosis at a six-month post-treatment evaluation appeared to be good. CLINICAL
      SIGNIFICANCE: Dens invaginatus requires an early diagnosis and treatment. It may
      result in radicular and periapical pathosis requiring a combined non-surgical and
      surgical endodontic approach to treatment.

PMID- 19838615
TI  - Microscope-enhanced periodontal therapy: a review and report of four cases.
AB  - AIM: The aim of this report is to review the status of the use of surgical
      microscopes and microsurgery and their clinical application in the field of
      periodontics. BACKGROUND: The use of magnification systems and periodontal
      microsurgery are part of a broad movement in dentistry toward the use of
      minimally invasive procedures to replace the need for more extensive surgical
      procedures. While magnification systems are widely used in endodontics, their
      application in periodontics is still in its nascent phase. However, clinicians
      have reported that use of magnification facilitates the use of minimal invasive
      periodontal surgery. TECHNIQUE: The surgical microscope is an invaluable aid for
      periodontists in the diagnosis and treatment of periodontal disease. Magnified
      vision used in conjunction with microsurgical instruments and techniques can lead
      to a higher quality of care and an improved surgical outcome. SUMMARY: Surgical
      operating microscopes have shown promising results in the hands of periodontists
      who are properly trained in their use. Despite the apparent advantages, there is
      still a lack of "high level of evidence" in the form of controlled clinical
      trials to estimate the magnitude of the real benefits of the microsurgical
      approach over the conventional approach. CONCLUSION: The scientific community
      understands the need for more investigations to completely understand the
      conditions that would best favor the creation of a tooth substitute. Recent gains
      in the understanding of the molecular regulation of tooth morphogenesis, stem
      cell biology, and biotechnology offers the opportunity to realize this goal.
      CLINICAL SIGNIFICANCE: Even though all the procedures shown in this review can be
      performed using normal vision, performing these procedures using a surgical
      microscope and microsurgical instruments offers definite advantages in terms of
      improved visual acuity, superior approximation of wounds, rapid wound healing,
      decreased post-operative morbidity, and increased acceptance by the patients.

PMID- 19838616
TI  - AAOMP case challenge: A nonulcerated, slowly growing mass of the mandible.
AB  - A 38-year-old male presented with a slowly growing mass of the right mandible.
      The lesion displaced the mandibular canine and premolar teeth on the same side.

PMID- 19838617
TI  - Acetaminophen at different doses protects brain microsomal Ca2+-ATPase and the
      antioxidant redox system in rats.
AB  - Acetaminophen, an analgesic and antipyretic drug, rescues neuronal cells from
      mitochondrial redox impairment and reactive oxygen species (ROS). Excessive
      administration of acetaminophen above the recommended daily dose range has some
      negative effects on the brain. We investigated the effects of different doses of
      acetaminophen on Ca(2+)-ATPase and the antioxidant redox system in rats. Seventy
      rats were randomly divided into seven equal groups. The first was used for the
      control. One dose of 5, 10, 20, 100, 200, and 500 mg/kg acetaminophen was
      intraperitoneally administered to rats constituting the second, third, fourth,
      fifth, sixth, and seventh groups, respectively. After 24 h, brain cortical
      samples were taken and brain microsomal samples were obtained by
      ultracentrifugation. Brain and microsomal lipid peroxidation (LP) and brain
      calcium levels in the sixth and seventh groups were increased compared to
      control. LP levels in the second, third, and forth groups; brain vitamin E
      levels; brain and microsomal glutathione peroxidase (GSH-Px); and Ca(2+)-ATPase
      activity in the sixth and seventh groups were lower than in control, although
      brain vitamin E concentrations in the second, third, fourth, and fifth groups and
      microsomal GSH-Px activity in the third and fourth groups were higher than in
      control. Brain cortical beta-carotene and vitamin A concentrations did not differ
      in the seven groups. In conclusion, 5-100 mg/kg acetaminophen seems to have
      protective effects on oxidative stress-induced brain toxicity by inhibiting free
      radicals and supporting the antioxidant redox system.

PMID- 19838618
TI  - Effect of probiotic supplementation on immunoglobulins, isoagglutinins and
      antibody response in children of low socio-economic status.
AB  - BACKGROUND: Antigen exposure is one of the major exogenous factors modulating
      human immunocompetence acquisition. Decline in family size and improvements in
      public health and hygiene in developed countries, may deprive the immune system
      of appropriate antigen input by diminishing infectious stimuli. Probiotics are a
      large group of microorganisms defined by their beneficial effects on human health
      and with stimulating effects on different functions of the immune system. AIM OF
      THE STUDY: We conducted a double-blind, placebo-controlled trial to determine if
      probiotics maintain their immune-stimulating effects in a population of 162
      children with a high index of natural exposure to microorganisms. Children were
      to ingest for at least 4 months one of two products, low-fat milk fermented by
      Streptococcus thermophilus (control product) or low-fat milk fermented by S.
      thermophilus and Lactobacillus casei, with Lactobacillus acidophilus,
      oligofructose and inulin added after the fermentation process (test product).
      According to their age, children were vaccinated with DTP-Hib vaccine or a 23
      valent anti-pneumococcal vaccine. RESULTS: Final analysis of results was done in
      70 children in each group, showing that the rate of immunoglobulin and
      isoagglutinin acquisition was similar in both groups. There was no difference
      between groups in antibody levels neither before nor after vaccination. Days of
      fever and number of episodes of infection were not statistically different in
      either group. CONCLUSIONS: Supplementation of standard fermented milk with
      additional probiotics was not of benefit. The high natural rate of early
      microbial exposure in infants and children from a population of low socio
      economic status living in a "less hygienic environment" may account for the
      absence of an additional immune-stimulating effect by supplementary probiotics.

PMID- 19838619
TI  - Complete nucleotide sequence of the Toledo isolate of turnip ringspot virus.
AB  - The complete genomic sequence of the Toledo isolate of the comovirus, turnip
      ringspot virus (TuRSV), was found to consist of 2 polyadenylated RNAs. RNA 1 is
      6082 nucleotides long and encodes a single predicted polypeptide of 1860 amino
      acids. The predicted RNA 1 polyprotein contains the polypeptides for viral
      replication and proteolytic processing. RNA 2, that is 3985 nucleotides long,
      codes for a single predicted 1095 amino acid polypeptide containing the movement
      and coat proteins. Phylogenetic analysis indicates that TuRSV is most closely
      related to radish mosaic virus, and these crucifer-infecting pathogens form a
      distinct clade within the comoviruses.

PMID- 19838620
TI  - Genetic variability and phylogenetic analysis of hosta virus X.
AB  - Triple gene block 1 (TGB1) and coat protein (CP) sequences of 30 hosta virus X
      (HVX) isolates from Tennessee (TN), USA, were determined and compared with
      available sequences in GenBank. The CPs of all known HVX isolates, including
      those from TN, shared 98.3-100% and 98.2-100% nucleotide and amino acid sequence
      identity, respectively, whereas TGB1 shared 97.4-100% nucleotide and 97-100%
      amino acid sequence identity. TGB1 of TN isolates were all longer by one codon
      from that of a Korean isolate, which is the only sequence publicly available.
      Phylogenetic analysis of nucleotide and amino acid sequences of TGB1 and CP of
      all known HVX isolates, separately or combined, revealed a close relationship,
      suggesting that all of them are derived from a common ancestor. Phylogenetic
      analysis with the type member of each genus of the family Flexiviridae confirmed
      that HVX is a member of a distinct species of the genus Potexvirus.

PMID- 19838621
TI  - B7-DC-silenced dendritic cells induce stronger anti-HBV immunity in transgenic
      mice.
AB  - Hepatitis B virus (HBV) is a noncytopathic DNA virus and is the pathogen of acute
      and chronic hepatitis. Interferon and nucleotide analogues such as lamivudine and
      adefovir are the current treatment strategies of HBV infection; however, it is
      still a serious disease. Therefore, the development of new therapeutic options
      against HBV is needed. In the present study, we have investigated whether the
      vectors carrying short hairpin RNA (shRNA) targeting the murine B7-DC gene could
      silence the expression of B7-DC and analyzed the function of gene-modified
      dendritic cells (DCs) by mixed lymphocyte reaction. The results demonstrated that
      two shRNA vectors efficiently suppressed the expression of B7-DC. The MLR assay
      showed that shRNA-B7-DC-transfected DCs induced markedly higher allogeneic
      lymphocyte proliferation than transfected DCs with the vector plasmid pAS and
      untreated DCs at all dilutions. The most efficient shRNA plasmid vector against
      B7-DC was then used to silence the expression of B7-DC on DCs, the gene-modified
      DCs were pulsed with HBV-specific peptides, and HBV transgenic mice were
      immunized. After three rounds of immunization, the splenocytes were stimulated in
      vitro and tested for cytotoxicitic T lymphocyte activity, while the sera were
      used to detect the level of HBsAg and HBV DNA. The data demonstrated that
      blockade of B7-DC on DCs augmented the cytolytic activity induced by immunization
      with peptide-pulsed DCs and significantly reduced the concentration of serum
      HBsAg and HBV DNA, suggesting that silencing of B7-DC is of potential value in DC
      based therapy of HBV infection.

PMID- 19838622
TI  - Dementia and capsular genu ischemia in patients with severe bacterial meningitis.
AB  - Infarction in the genu of the internal capsule causes dementia that is
      characterized by abulia, lethargy and memory loss without obvious motor palsy
      (capsular genu syndrome). We found infarction or decreased cerebral blood flow in
      the genu of the internal capsule in 6 of 13 patients with severe bacterial
      meningitis. Four of these six patients developed post-meningitis dementia,
      characterized by abulia, lethargy, and memory loss. Of 24 patients with viral
      meningitis, none developed capsular genu ischemia or post-meningitis dementia. In
      patients with severe bacterial meningitis, capsular genu ischemia may play some
      role in the development of post-meningitis dementia. In patients with viral
      meningitis, absence of such ischemia may explain, at least in a part, the rarity
      of post-meningitis dementia.

PMID- 19838623
TI  - The first case history of multiple sclerosis: Augustus d'Este (1794-1848).
AB  - The personal diary of Sir Augustus d'Este, born 1794 grandson of King George III
      of England, reveals a medical history strongly suggesting that Augustus suffered
      from multiple sclerosis (MS). It could well be the first record of a person
      having this disease. Charcot coined the term sclerose en plaques 20 years after
      the death of this patient in 1848. The onset of this man's MS seems to have been
      in 1822 with bilateral optic neuritis, the disease gradually developing in the
      classic manner with bouts derived from different loci in the central nervous
      system and eventually a secondary progressive form with paraparesis, sphincter
      incontinence, urinary problems and impotence. In 1941, Firth highlighted the case
      of Augustus d'Este and later wrote a description of the pathology including a
      discussion on the aetiology of MS. No previous medical records have given such a
      characteristic picture of MS as this.

PMID- 19838624
TI  - Alzheimer's disease and endothelial dysfunction.
AB  - Recent studies suggest strong interactions between cerebrovascular and
      Alzheimer's disease (AD) pathology. These conditions share common risk factors
      and individuals having both frequently show greater cognitive impairment than
      those affected by only one disease. Many studies point to early vascular
      dysregulations in AD. The exchange between vascular and neural cells occurs
      through mechanisms not completely understood, involving interactions among
      endothelial, glial, neuronal and smooth muscle cells within the neurovascular
      unit. Studies suggest that the dysregulation of the unit is likely associated
      with hypertension and other systemic diseases. Associations between hypertension
      and cognitive decline are not established, but other variables associated with
      hypertension could create a causal link. Many studies have lacked a consistent,
      quantitative neuropsychological approach for assessing cognitive functions. This
      approach is reductive, as the need for a formal neuropsychological assessment has
      gained broad recognition, and the definition of dementia has gone through
      revision processes, which are in progress.

PMID- 19838625
TI  - Topiramate in migraine progression.
AB  - Increasing evidence shows that migraine, typically considered as an episodic
      disease, is a chronic and, in some patients, progressive disorder. Among
      neuromodulators used for migraine prevention, topiramate has a high level of
      evidence-based efficacy. Through its wide range of mechanisms of action
      topiramate increases the activation threshold resulting in neuronal stabilization
      and thereby reducing cortical neurons hyperexcitability, which is believed to be
      an important electrophysiological feature underlying the pathogenesis of epilepsy
      and migraine. Recent studies show that migraineurs have subclinical structural
      brain changes and persistent alteration of pain perception, in some cases
      correlated with the duration of the disease and the frequency of attacks that
      might play a role in the transformation of episodic migraine to chronic forms. An
      early and prolonged preventive treatment might reduce the risk of such
      transformation. Recent evidence suggests that topiramate, by reducing migraine
      frequency and use of acute medication, may prevent the negative progression of
      migraine. Furthermore, two recently completed multicenter, randomised, placebo
      controlled trials have shown that treatment with topiramate 100 mg/day is
      effective and well tolerated in patients already progressed to chronic migraine
      and difficult to treat conditions associated with medication-overuse. Topiramate
      seems to be a preventive treatment, which might be able to act at different
      levels of the migraine cycle: reduction of frequency in episodic migraine,
      prevention, and treatment of chronic migraine.

PMID- 19838626
TI  - Successful treatment of nonocclusive mesenteric ischemia that developed during
      the peritransplant period following ABO-incompatible kidney transplantation.
AB  - Nonocclusive mesenteric ischemia (NOMI) is an infrequent and fatal disorder. We
      describe a 54-year-old man who developed NOMI during the peritransplant period
      following ABO-incompatible living-donor kidney transplantation, but who was
      successfully treated with his renal graft function unimpaired. Abdominal pain
      appeared on the sixth postoperative day (POD), and emergency surgery was
      performed on POD 8. Discontinuous segmental necrosis extended throughout the
      small intestine, and the necrotic segments were entirely removed. He thereafter
      had ischemia of the ascending colon, which was treated with colectomy, and
      prostaglandin E1 delivered through the related artery prevented advanced
      necrosis. Temporary colostomy was closed 20 months after surgery. He maintains
      excellent graft function at present without secondary disorder. There has been no
      ABO-incompatible kidney transplant recipient complicated with NOMI. However,
      patients with end-stage renal disease are at the highest risk for this lethal
      condition, and physicians and urologists should correctly recognize its
      diagnostics and therapeutics.

PMID- 19838627
TI  - The role of salvage reirradiation for malignant gliomas that progress on
      bevacizumab.
AB  - Bevacizumab and irinotecan are effective against recurrent malignant gliomas.
      However, at subsequent progression, patients rarely respond to a second
      bevacizumab-containing chemotherapeutic regimen. Salvage re-irradiation with
      bevacizumab for recurrent but bevacizumab naive malignant gliomas showed
      encouraging results. We performed a retrospective review of the medical records
      of 23 patients treated with either fractionated stereotactic radiotherapy (FSRT)
      or stereotactic radiosurgery (SRS) after progression on an initial bevacizumab
      regimen. Patients were treated after re-irradiation with bevacizumab but combined
      with a different chemotherapy. We then compared them to another 23 patients who
      progressed on an initial bevacizumab + chemotherapy regimen. These patients did
      not receive re-irradiation but bevacizumab was continued combined with a
      different chemotherapy. Patients treated with FSRT/SRS/bevacizumab had a longer
      median progression-free period (2.6 vs. 1. 7 months, P = 0.009), longer median
      post FSRT/SRS treatment survival (7.2 vs. 3.3 months, P = 0.03) and higher
      radiographic response rate (22 vs. 0%, P = 0.049). FSRT or SRS followed by
      bevacizumab + chemotherapy may have a role for patients who progress on
      bevacizumab.

PMID- 19838628
TI  - Metabolic engineering of Streptomyces venezuelae for malonyl-CoA biosynthesis to
      enhance heterologous production of polyketides.
AB  - Using metabolic engineering, we developed Streptomyces venezuelae YJ028 as an
      efficient heterologous host to increase the malonyl-CoA pool to be directed
      towards enhanced production of various polyketides. To probe the applicability of
      newly developed hosts in the heterologous production of polyketides, we expressed
      type III polyketide synthase, 1,3,6,8-tetrahydroxynaphthalene synthase, in these
      hosts. Flaviolin production was doubled by expression of acetyl-CoA carboxylase
      (ACCase) and 4-fold by combined expression of ACCase, metK1-sp and afsR-sp. Thus,
      the newly developed Streptomyces venezuelae YJ028 hosts produce heterologous
      polyketides more efficiently than the parent strain.

PMID- 19838629
TI  - A novel bioreactor for immobilized phototrophs.
AB  - A novel configuration of photobioreactor is described in which filaments of
      alginate containing immobilized cells of a leaky mutant of Dunaliella parva are
      wound round a central light well which is located within a glass outer chamber so
      that a liquid medium is caused to flow in the annular space between the outside
      chamber and the alginate filaments. Glycerol production by D. parva was
      maintained for 700 h and the highest concentration of glycerol attained was
      approx. 12 mg l(-1).

PMID- 19838630
TI  - Ammonium and phosphate limitation in 1,3-propanediol production by Klebsiella
      pneumoniae.
AB  - Excretion of 1,3-propanediol (1,3-PD) by K. pneumoniae was compared in ammonium-
      and phosphate-limited chemostat cultures running with an excess of glycerol. 59
      and 43% catabolic flux were directed to 1,3-PD in ammonia-limited cultures and
      phosphate-limited cultures at dilution rate of 0.1 h(-1), respectively. Ammonia
      limited fed-batch cultures produced 61 g 1,3-PD l(-1) and a total of 15 g l(-1)
      organic acid in 36 h. However, phosphate-limited fed-batch cultures excreted 61 g
      lactate l(-1) and 44 g 1,3-PD l(-1).

PMID- 19838631
TI  - Quantitation of non-amplified genomic DNA by bead-based hybridization and
      template mediated extension coupled to alkaline phosphatase signal amplification.
AB  - Klenow I polymerase activity was combined with solid phase DNA hybridization to
      detect non-amplified genomic DNA (gDNA) sequences from Escherichia coli.
      Aminopropyl-controlled pore glass surface-bound oligonucleotides were hybridized
      to fragmented gDNA. The template-mediated extension at the 3'-terminus of the
      immobilized probe was then promoted in the presence of Klenow I polymerase and
      digoxigenin-labeled nucleotides. Detection of the extended probes was
      accomplished with an anti-digoxigenin alkaline phosphatase conjugate protocol
      coupled to colorimetric or fluorescent detection. Using the colorimetric
      protocol, the proof-of-concept was established. The fluorescence-based
      methodology, on the other hand, provided the basis for a quantitative
      interpretation of the data, affording a detection limit of 5 pM gDNA.

PMID- 19838632
TI  - Characterisation and expression of a novel holotype crystal protein gene,
      cry56Aa1, from Bacillus thuringiensis strain Ywc2-8.
AB  - Bacillus thuringiensis isolate Ywc2-8, from soil in Sichuan Basin in western
      China, contains a spherical crystal harbouring two insecticidal crystal proteins
      with masses of 70 kDa and 130 kDa. A novel cry-type gene, encoding a 664 amino
      acid protein with 34% homology to cry29Aa1, was found and cloned from this
      strain. This gene belongs to a novel holotype cry and is designated as cry56Aa1.
      It was expressed in E. coli. Insecticidal activity assays showed that recombinant
      Cry56Aa1 was toxic to both Dipteran (Aedes aegypti) and Lepidopteran (Plutella
      xylostella and Helicoverpa armigera) pests. Cloning of this gene may help to
      overcome the increasing resistance of pests to currently used insecticides.

PMID- 19838633
TI  - New insights on O2 uptake mechanisms in two-phase partitioning bioreactors.
AB  - Numerous reports show that both transfer and uptake of poorly-water soluble
      substrates are significantly enhanced in two-phase partitioning bioreactors
      (TPPBs). A number of hypotheses have been put forward to explain these
      enhancements and among them, the occurrence of direct substrate or oxygen uptake
      from the vector/water interface has been suggested. The objective of this paper
      was to quantify the direct oxygen uptake from the vector/water interface in a
      culture of Pseudomonas putida, performed in a stirred tank reactor, using glucose
      as substrate and silicone oil as vector. Despite of a sufficient dissolved O(2)
      concentration in the vector phase (17 mg l(-1)) and a significant vector surface
      area (4,000 m(-1)) no significant direct O(2) uptake from the vector/water
      interface was observed, compared to O(2) uptake from the aqueous phase. From
      these results it was concluded that, direct O(2) or substrate uptake from the
      vector/water interface might not be significant in TPPBs.

PMID- 19838634
TI  - Recombinant canstatin inhibits tumor growth in an orthotopic AT-84 oral squamous
      cell carcinoma model.
AB  - The inhibitory effect of recombinant canstatin on tumor growth was investigated
      using an orthotopic oral squamous cell carcinoma (AT-84 cells) animal (C3H/HeN)
      model. Recombinant canstatin from stably transfected Drosophila S2 cells was
      purified to homogeneity using a simple one-step Ni NTA affinity fractionation. In
      our oral cancer model, the final volume and weight of tumors in groups treated
      with purified canstatin were both reduced to 44% of values for a control group
      treated with PBS. Blood or lymphatic vessel densities of tumors in the canstatin
      treated group were reduced to 72% and 44% of control group values, respectively.
      Recombinant canstatin at 20 microg/ml effectively inhibited tube formation in
      HUVEC and lymphatic endothelial cells. Our results show that recombinant
      canstatin has anti-tumoral effects against primary oral squamous cell carcinoma.

PMID- 19838635
TI  - Conversion of alpha-amyrin into centellosides by plant cell cultures of Centella
      asiatica.
AB  - Plant cell cultures of Centella asiatica produce small quantities of
      centellosides: madecassosid > asiaticosid > madecassic acid > asiatic acid. To
      obtain a more efficient production system of these bioactive triterpenoid
      compounds, we developed a process where the substrate, alpha-amyrin, was
      converted into centellosides by cell suspensions of C. asiatica. When alpha
      amyrin in acetone was added at 0.01 mg/ml(-1) to the culture medium, together
      with the permeabilizing agent DMSO, after 7 days nearly 50% had penetrated the
      plant cells, of which almost 84% was transformed into centellosides. The system
      therefore efficiently converts alpha-amyrin into centellosides, thus opening a
      new possibility for the production of these compounds.

PMID- 19838636
TI  - Molecular characterization of OsPAP2: transgenic expression of a purple acid
      phosphatase up-regulated in phosphate-deprived rice suspension cells.
AB  - A phosphate starvation-induced, purple, acid phosphatase cDNA was cloned from
      rice, Oryza sativa. The cDNA encoding the phosphatase (OsPAP2) has 1,893 bp with
      an open reading frame of 630 amino acid residues. The deduced amino acid sequence
      of OsPAP2 shows identities of 60-63% with other plant purple acid phosphatases
      and appears to have five conserved motifs containing the residues involved in
      metal binding. OsPAP2 expression is up-regulated in the rice plant and in cell
      cultures in the absence of phosphate (P( i )). The induced expression of OsPAP2
      is a specific response to P( i ) starvation, and is not affected by the
      deprivation of other nutrients. OsPAP2 expression was responsive to the level of
      P( i )-supply, and transcripts of OsPAP2 were abundant in P( i )-deprived roots.
      The OsPAP2 cDNA was expressed as a 69 kDa polypeptide in baculovirus-infected
      insect Sf9 cells. In addition, the OsPAP2 gene was introduced into Arabidopsis
      via an Agrobacterium-mediated transformation. Functional expression of the OsPAP2
      gene in the transgenic Arabidopsis line was confirmed by northern and western
      blot analyses, as well as by phosphatase activity assays. These results suggest
      that the OsPAP2 gene can be used to develop new transgenic dicotyledonous plants
      that are able to adapt to P( i )-deficient conditions.

PMID- 19838637
TI  - Expression of Trichoderma reesei endo-beta-glucanase II in silkworm, Bombyx mori
      L. by using BmNPV/Bac-to-Bac expression system and its bioactivity assay.
AB  - The silkworm, Bombyx mori, was used to produce recombinant endo-beta-glucanase II
      (rEGII). The EGII gene (egl2) was cloned from the cellulolytic fungus Trichoderma
      reesei and inserted into B. mori nucleopolyhedrovirus (BmNPV) genome using
      BmNPV/Bac-to-Bac expression vector. For expression of rEGII, both the BmN cells
      and B. mori larvae were infected with the recombinant virus. The putative rEGII
      yield was about 386 microg per larva and the enzyme activity of the purified
      rEGII was approx 352 U/mg of rEGII. The optimal activity of this purified protein
      was observed at 55 degrees C and pH 4, respectively.

PMID- 19838638
TI  - L-arginine reverses cigarette-induced reduction of fractional exhaled nitric
      oxide in asthmatic smokers.
AB  - INTRODUCTION: Complex mechanisms regulate nitric oxide (NO) synthesis. Cigarette
      smoking decreases fractional exhaled NO (FE(NO)), while asthmatic inflammation
      increases FE(NO). To assess whether the smoking-induced decrease in FE(NO) levels
      was reversible, asthmatic and non-asthmatic smokers inhaled the NO synthase (NOS)
      substrate, L-arginine. Aminoguanidine, a relatively selective Type II NOS
      inhibitor, was used also to assess the role of NOS subtypes in these changes of
      FE(NO). METHODS: The study was a single-blinded, placebo-controlled, cross-over
      design in two parts. Part I: smoking asthmatic and non-asthmatic smoking subjects
      smoked one cigarette and then inhaled nebulised L-arginine or L-alanine
      (control). Spirometry, FE(NO), nasal NO (FN(NO)), FE(CO), were measured for 4 h.
      Part II: subjects inhaled nebulised aminoguanidine prior to an identical protocol
      as in Part I. Change in FE(NO) was assessed as area under the curve (AUC).
      RESULTS: Part I: In asthmatic smokers, cigarette smoking followed by L-arginine
      caused a significant median increase in AUC of 29.2(17)% FE(NO) change/hour (p =
      0.04), which did not occur in non-asthmatic smokers (baseline FE(NO) 12.7(7.1-18)
      vs. 6.7(4-9.2) ppb, respectively). Part II: Aminoguanidine prior to smoking
      caused a significant fall in FE(NO) in both asthmatic and non-asthmatic smokers.
      L-arginine showed significant reversal of this effect in both asthmatic and non
      asthmatic subjects. CONCLUSIONS: In asthmatic smokers, L-arginine increases
      FE(NO) after cigarette smoking but not in non-asthmatic smokers. The decrease in
      FE(NO) after aminoguanidine and subsequent partial reversal by L-arginine in both
      groups, suggests that Type II NOS contributes to the FE(NO) in both.

PMID- 19838640
TI  - Compression fractures of the vertebrae during a "bumpy" boat ride.
AB  - INTRODUCTION: Compression fracture of the vertebrae is common, often the result
      of falls from height and motor vehicle accidents in the younger age groups. It
      can occur following minor trauma in the elderly and in those with osteoporosis.
      MATERIALS AND METHODS: We present an interesting case of compression fracture of
      the vertebral bodies occurring simultaneously in a couple during a boat ride
      while on holiday. One individual had fracture of the T8, while the other
      fractured the L1 vertebrae. Both injuries were treated conservatively with Taylor
      braces. CONCLUSION: We highlight one of the potential hazards of this
      recreational activity, and the almost identical fracture pattern in this couple.

PMID- 19838639
TI  - Imaging in targeted delivery of therapy to cancer.
AB  - We review the current status of imaging as applied to targeted therapy with
      particular focus on antibody-based therapeutics. Antibodies have high tumor
      specificity and can be engineered to optimize delivery to, and retention within,
      the tumor. Whole antibodies can activate natural immune effector mechanisms and
      can be conjugated to beta- and alpha-emitting radionuclides, toxins, enzymes, and
      nanoparticles for enhanced therapeutic effect. Imaging is central to the
      development of these agents and is used for patient selection, performing
      dosimetry and assessment of response. gamma- and positron-emitting radionuclides
      may be used to image the distribution of antibody-targeted therapeutics While
      some radionuclides such as iodine-131 emit both beta and gamma radiation and are
      therefore suitable for both imaging and therapy, others are more suited to
      imaging or therapy alone. Hence for radionuclide therapy of neuroendocrine
      tumors, patients can be selected for therapy on the basis of gamma-emitting
      indium-111-octreotide imaging and treated with beta-emitting yttrium-90
      octreotate. Positron-emitting radionuclides can give greater sensitivity that
      gamma-emitters but only a single radionuclide can be imaged at one time and the
      range of radionuclides is more limited. The multiple options for antibody-based
      therapeutic molecules, imaging technologies and therapeutic scenarios mean that
      very large amounts of diverse data are being acquired. This can be most
      effectively shared and progress accelerated by use of common data standards for
      imaging, biological, and clinical data.

PMID- 19838641
TI  - Hypertension in Ireland: public awareness and doctors choice of therapy.
AB  - BACKGROUND: Hypertension is the commonest medical condition in Ireland. AIMS: (1)
      To examine the level of awareness of blood pressure (BP) in the population and
      (2) to ascertain the opinion of general practitioners (GPs) in diagnosis and
      management of hypertension. METHODS: BP measurements and assessment of BP
      awareness were performed in a sub-sample of the general population (n = 1,071).
      The opinion of GPs (n = 1,037) on hypertension was determined in a postal survey.
      RESULTS: Amongst the population sampled (45 +/- 13 years, mean age +/- SD),
      almost half had elevated BP (>140/90 mmHg) but only half of those were already on
      antihypertensives. 40% had no knowledge of their BP and 54% were not aware of
      what constituted normal BP. While some 80% of GPs said they followed British
      guidelines, their practice was more in keeping with the European guidelines.
      Approximately, 90% of GPs required ambulatory BP recording to confirm diagnosis
      of hypertension. First choice antihypertensive agents were ACE inhibitors and
      angiotensin receptor antagonists in younger patients and diuretics and ACE
      inhibitors in older patients. CONCLUSION: These results suggest that there is a
      need for further public education on BP and nationally agreed hypertension
      guidelines.

PMID- 19838642
TI  - Inhibition of both thioredoxin reductase and glutathione reductase may contribute
      to the anticancer mechanism of TH-302.
AB  - Selenium-containing thioredoxin reductase (TrxR) is an important target of cancer
      therapy. Many useful anticancer agents including bis-alkylating agents,
      cisplatin, and arsenic trioxide are known to interact with the selenocysteine
      dipeptide in the carboxy terminal region of thioredoxin reductase and inactivate
      its ability to reduce thioredoxin. Some investigators have postulated that the
      inactivation of TrxR may add to the cytotoxic potential of these anticancer
      agents. TH-302 is a newly developed antineoplastic drug which represents a
      potential new class of tumor selective hypoxia-activated prodrugs (HAPs). TH-302
      is an inactive prodrug created by the covalent conjugation of 2-nitroimidazole as
      an oxygen sensor to bromo-isophosphoramide (Br-IPM). In the presence of severe
      hypoxia and near anoxia, the two imidazole sensor moiety undergoes reduction and
      the Br-IPM is released in situ. Bromo-IPM is a more potential analog of Chloro
      IPM, the active alkylating moiety that is derived by activation of ifosfamide
      (IFO). We previously demonstrated that IFO could inhibit tumor TrxR activity and
      chloro-IPM is known to bind covalently to the seleno-cysteine dipeptide in
      thioredoxin reductase. The present study assessed the ability of TH-302 to
      activate in the tumors of mice-bearing hepatoma 22 (H22) and inactivate the tumor
      TrxR. In mice-bearing hepatoma 22 (H22) solid tumors, intraperitoneal (i.p.)
      injection with TH-302 at the dose of 200 mg/kg administered twice, a regimen
      which was well tolerated by the mice, significantly inhibited tumor growth. Also
      in this mice model, i.p. TH-302 at the dose of 300 mg/kg, which would be the
      maximum single i.p. administration dose tolerated by mice, and which induced only
      2% body weight loss, significantly inhibited both TrxR and glutathione reductase
      (GR) activities by 46% (P < 0.001) and 60% (P < 0.001) as compared with the
      controls, respectively, at 3 h after the injection. Since TrxR is a key player in
      thioredoxin system and GR is the major reductase for the reduction of oxidized
      glutathione in glutathione system, the present results imply the anticancer
      effect of TH-302 is associated concurrently with modulation of TrxR and GR. These
      findings suggest that the anticancer activity of TH-302 in this model system may
      associate with both DNA alkylation and the modulation of TrxR and GR. In
      addition, they suggest that, by inhibition of these two critical reductases, with
      less glutathione available to intercept the reactive intermediates involved in
      DNA alkylation, the antitumor effects of the chemotherapy would be enhanced.

PMID- 19838643
TI  - [Erythrocyte transfusion: update of the guidelines "therapy with blood components
      and plasma derivatives"].
AB  - The new version of the guidelines, which have now been renamed Cross-sectional
      guidelines on therapy with blood components and plasma derivatives, is
      distinguished by focusing on key recommendations. In each section clear
      recommendations for the selection and indications for the use of each blood
      product are presented and these recommendations are classified with respect to
      their strength and evidence level. The most important recommendations in section
      1 "Erythrocyte concentrates", which is especially important for the faculty of
      anesthesiology, will be presented in this article with special reference to the
      data on which the recommendations are based.

PMID- 19838645
TI  - High fusion rates with circular plate fixation for four-corner arthrodesis of the
      wrist.
AB  - BACKGROUND: Scaphoid excision and four-corner fusion is commonly performed to
      reconstruct advanced scapholunate collapse and scaphoid nonunion with collapse.
      Metallic plates were introduced for achieving fixation of the four carpal bones.
      Although the developer reported high rates of fusion, several other early reports
      of circular plate fixation suggest higher complication rates and inferior
      outcomes compared with traditional fixation techniques. QUESTIONS/PURPOSES: To
      clarify the controversy in the literature we determined the fusion rates,
      complications, and functional outcomes of patients having circular plate fixation
      for four-corner fusion. METHODS: We retrospectively reviewed 15 patients treated
      for radioscaphoid arthritis with four-corner fusion using circular plate
      fixation. The minimum followup was 11 months (mean, 22 months; range, 11-39
      months). RESULTS: Radiographic union was achieved by all 15 patients. There was
      only one postoperative complication. ROM was 71% and grip strength was 78% of the
      opposite normal side. CONCLUSIONS: Our results compare favorably with those using
      traditional fixation techniques. ROM measurements seem superior to those reported
      in the literature. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 19838644
TI  - Cerebral microembolization during primary total hip arthroplasty and
      neuropsychologic outcome: a pilot study.
AB  - BACKGROUND: Intraoperative cerebral microembolization occurs in a substantial
      proportion of patients undergoing THA. Historically, postoperative cognitive
      dysfunction has been attributed to different factors, including anesthesia, but
      the influence of the surgery has not been thoroughly examined.
      QUESTIONS/PURPOSES: We conducted a prospective, controlled clinical trial to
      assess intraoperative cerebral microembolization during THA and neuropsychologic
      outcome. METHODS: The presence of a patent foramen ovale (PFO) also was
      investigated, using transcranial Doppler, to determine whether this affected
      cerebral microembolic incidence and load and whether microemboli occurred as a
      result of specific surgical activity. Forty-five patients were recruited who
      underwent THA and neuropsychologic assessment; a battery of tests was
      administered preoperatively and at 6 weeks and 6 months postoperatively. RESULTS:
      Overall, patients showed improvement in total neuropsychologic change scores at
      both postoperative intervals. The incidence of cerebral microembolization for THA
      was 23%. The prevalence of PFO was 37%. PFO did not appear to influence
      microemboli load or incidence. More microemboli were seen during femoral
      component insertion and impaction. CONCLUSIONS: Intraoperative cerebral
      microembolization occurs in a substantial proportion of patients during THA
      recorded by transcranial Doppler. The microemboli load is low and is not
      influenced by the presence of PFO. Certain surgical activities seem responsible
      for greater cerebral microemboli generation. However, neuropsychologic outcome
      was not affected postoperatively by microemboli or other operative or patient
      variables.

PMID- 19838646
TI  - Necrotizing fasciitis of the extremity caused by Haemophilus influenzae serotype
      b in a healthy adult.
AB  - Haemophilus influenzae is a rare cause of necrotizing fasciitis with only a few
      previously reported cases. We describe the case of a 44-year-old man who had
      necrotizing fasciitis of the right lower extremity develop after intramuscular
      injections of paracetamol on his right buttock. The causative organism isolated
      was Haemophilus influenzae serotype b. This unusual infection was treated with
      repeated debridement and culture-guided antibiotics. There was no recurrence of
      infection at last followup 1 year after the initial surgery. Wound coverage was
      achieved with the use of a full-thickness skin graft after application of
      platelet-rich plasma and a dermal regeneration template. This resulted in a
      cosmetically acceptable appearance of the involved extremity for our patient.

PMID- 19838648
TI  - A simplified method for the measurement of insoluble solids in pretreated biomass
      slurries.
AB  - The biochemical conversion of cellulosic biomass to liquid transportation fuels
      includes the breakdown of biomass into its soluble, fermentable components.
      Pretreatment, the initial step in the conversion process, results in
      heterogeneous slurry comprised of both soluble and insoluble biomass components.
      For the purpose of tracking the progress of the conversion process, it is
      important to be able to accurately measure the fraction of insoluble biomass
      solids in the slurry. The current standard method involves separating the solids
      from the free liquor and then repeatedly washing the solids to remove the soluble
      fraction, a laborious and tedious process susceptible to operator variations. In
      this paper, we propose an alternative method for calculating the fraction of
      insoluble solids which does not require a washing step. The proposed method
      involves measuring the dry matter content of the whole slurry as well as the dry
      matter content in the isolated liquor fraction. We compared the two methods using
      three different pretreated biomass slurry samples and two oven-drying techniques
      for determining dry matter content, an important measurement for both methods. We
      also evaluated a large set of fraction insoluble solids data collected from
      previously analyzed pretreated samples. The proposed new method provided
      statistically equivalent results to the standard washing method when an infrared
      balance was used for determining dry matter content in the controlled measurement
      experiment. Similarly, in the large historical data set, there was no statistical
      difference shown between the wash and no-wash methods. The new method is offered
      as an alternative method for determining the fraction of insoluble solids.

PMID- 19838647
TI  - Statin use is associated with a significant reduction in cholesterol content of
      erythrocyte membranes. A novel pleiotropic effect?
AB  - PURPOSE: High cholesterol content of erythrocyte membranes (CEM) levels is
      present in patients with acute coronary syndromes (ACS). Intraplaque hemorrhage
      and erythrocyte lysis contribute to the deposition of cholesterol on the
      atherosclerotic plaque and to plaque rupture. With the present study we assessed
      the effect of statin therapy on CEM levels, a novel marker of coronary artery
      disease (CAD) instability during a 1-year follow-up in CAD patients. METHODS: 212
      consecutive eligible (158 men, 62 +/- 10 years) patients undergoing diagnostic
      coronary angiography for the assessment of angina pectoris were assessed. The
      study population comprised of 84 chronic stable angina (CSA) patients and 128 ACS
      patients. All study participants were commenced on statin treatment in equipotent
      doses and were followed for up to 1 year (at - 1, - 3, - 6 and - 12 months).
      RESULTS: Repeated measurements analysis of variance after appropriate adjustment
      showed a significant decrease (p < 0.001) in CEM content during follow up. CEM
      levels were decreasing at each time point (1 month : 100 microg/mg 95%CI 94.3
      105.6, 3 months : 78.1 microg/mg 95%CI 73.2-83, 6 months : 67.2 microg/mg 95%CI
      63.1-71.2, 1 year : 45.3 microg/mg 95%CI 42.2-48.3) compared to admission (112.1
      microg/mg 95% CI 105.9-118.3) and to all previous measurements. CONCLUSIONS: The
      present study showed, that use of statins is associated with a reduction in CEM,
      an emerging marker of clinical instability and plaque vulnerability in CAD
      patients. The pleiotropic effects of statins at the cell membrane level represent
      a promising novel direction for research in CAD.

PMID- 19838649
TI  - Adherence to infliximab maintenance therapy and health care utilization and costs
      by Crohn's disease patients.
AB  - INTRODUCTION: Studies suggest infliximab decreases hospitalization and surgery
      rates in Crohn'fs disease (CD). The aim of this analysis was to evaluate
      adherence to infliximab maintenance therapy and the impact of medication
      adherence on health care utilization and costs by patients with CD. METHODS:
      Patients with CD who had at least four infliximab infusions (with the time
      between consecutive infusions < or =12 weeks for the first four infusions) during
      the first year following infliximab initiation (index date) were identified from
      the Integrated Health Care Information Service claims database (2002-2006).
      Nonadherence was defined as fewer than seven infliximab infusions in the first
      year. One-year health care resource utilization and costs (excluding infliximab
      drug and administration costs) were compared between adherent and nonadherent
      patients, with adjustment for baseline characteristics. RESULTS: A total of 571
      patients with CD who were receiving infliximab maintenance therapy were
      identified. The infusion-based nonadherence rate was 34.3% during the first year
      of therapy. The multivariate analysis demonstrated that compared with adherent
      patients, nonadherent patients were more likely to have been hospitalized (odds
      ratio [OR]=2.7 [all-cause] and OR=2.5 [CD-related]; both P<0.001). Compared with
      infliximab-adherent patients, adjusted medical costs by nonadherent patients were
      73% ($6,692) and 90% ($4,961) greater for all-cause and CD-related medical costs,
      respectively (both P<0.001), and adjusted hospitalization costs were 115%
      ($11,450) and 115% ($9,570) greater for all-cause and CD-related hospitalization
      costs, respectively (both P<0.001). CONCLUSION: More than one-third of patients
      on infliximab maintenance therapy were nonadherent to recommended maintenance.
      Further, nonadherence was associated with increased medical costs and a greater
      rate of hospitalization.

PMID- 19838650
TI  - [Novel vaccination concepts on the basis of modern insights into immunology].
AB  - Since their introduction more than 200 years ago, vaccines have prevented
      millions of deaths caused by infectious diseases. This progress was possible
      because these vaccines protect through antibodies, which are relatively easily
      stimulated. In the meantime, we understand that diseases such as AIDS,
      tuberculosis, malaria and hepatitis C cannot be tackled by these conventional
      approaches. Recent insights into immunology provide the basis for the development
      of custom-tailored vaccines to successfully combat these threatening infections.
      These new generation vaccines comprise components that modulate the mediators of
      immunity (B cells, T cells, antigen-presenting cells and cytokines) in such a way
      that the best possible immune response develops. Alternative application methods
      offer the possibility to further improve the immune response. Thus, hope remains
      that the remarkable increase in knowledge in the areas of immunology and
      infectious disease research will help to successfully control infectious
      diseases.

PMID- 19838651
TI  - [Guideline for the mathematical estimate of the migration of individual
      substances from organic materials in drinking water (Modelling guideline).
      Version as of October 7, 2008].

PMID- 19838652
TI  - [Surgical training using simulator. Virtual reality].
AB  - Learning of laparoscopic operative skills is often complex and time consuming
      resulting in a learning curve especially for novices in surgery. Virtual reality
      (VR) simulation was developed as an alternative to conventional training, such as
      active assistance and conventional laparoscopic training with artificially
      perfused organs (Pop-Trainer). VR simulation enables a wide range of repeatable
      laparoscopic techniques in variable virtual scenarios. For abdominal surgery four
      different simulation systems (MIST-VR(R), LapSim, Simsurgery, Lap-Mentor) are
      currently available and the modules allow simulation of abstract exercises to
      more advanced laparoscopic procedures, such as laparoscopic sigmoid resection.
      The effect of VR training on laparoscopic performance and its impact on non
      technical skills was evaluated using the simulator LapSim after a constructive
      validity study. Novices benefited most from VR training and performance in the
      operating room improved significantly after VR training. Good spatial perception
      and positive stress coping strategies also enhanced laparoscopic performance. VR
      simulation provides a tool to shift the laparoscopic learning curve outside the
      operating room and thus contributes to patient safety. It would be worthwhile to
      include VR training in the surgical curriculum. For economic reasons regional
      training centers seem to be an effective way to realize a broad implementation of
      VR simulation in surgical training. Application and development of VR simulators
      should be professionally promoted just as flight simulators in aviation.

PMID- 19838653
TI  - [The "invisible" foreign body].
AB  - A 58-year-old female patient fell down a stairs carrying a plant pot. The bamboo
      stem penetrated the left lower lip and remained stuck in the throat. The patient
      pulled the bamboo stem out immediately. The lower lip was sutured and a tear in
      the mucous membrane in the tonsils was explored and cleansed. A foreign body
      could not be detected either clinically or by computed tomography (CT) of the
      neck. After 1 week a control CT of the neck was carried out because the patient
      complained of odynophagy and a putrid taste. An initially overlooked foreign body
      was now detected in the "lung window" and lay in an abscess cavity on the
      prevertebral surface. The foreign body was surgically removed with the patient
      under narcosis and there were no aftereffects.

PMID- 19838654
TI  - [Stroke as manifestation of increased cardiovascular risk: an interdisciplinary
      challenge].

PMID- 19838655
TI  - [Chemotherapy of colorectal cancer].
AB  - Colorectal cancer (CRC) is the second leading cause of cancer death in the
      western world. Almost every second patient dies of the disease. The introduction
      of new and effective chemotherapeutic substances and biologics in the past decade
      has significantly improved the systemic treatment of patients with CRC. In stage
      III colon cancer combination chemotherapy with oxaliplatin is the standard of
      care. In stage IV cancer the choice of therapy is dependent on the clinical
      status of the patient. For some patients primary resection of metastases or
      resection after combination therapy and downsizing of lesions offers a chance for
      cure. In the palliative setting intensive combination treatment is indicated if
      the patient suffers from tumor related symptoms or a rapid progress of the
      disease. The aim of palliative therapy is the prolongation of survival and the
      improvement of quality of life. Combination with monoclonal antibodies leads to
      further improvement of survival. Furthermore, the introduction of the mutational
      status of the KRAS oncogene as the first predictive marker into clinical care is
      an important step towards the individualization of treatment in CRC.

PMID- 19838656
TI  - [Therapy of acute ischemic stroke].
AB  - New diagnostic and therapeutic developments have led to an innovative approach to
      stroke therapy. The slogan "time is brain" emphasizes that stroke is a medical
      emergency comparable to myocardial infarction. The stroke unit conception is an
      evidence based therapy for all stroke patients and improves outcome
      significantly. The monitoring of vital signs and the management of stroke
      specific complications are highly effective. Early secondary prophylaxis reduces
      the risk of recurrence. The effect of CT based thrombolysis within the time
      window of 4,5 h has been substantiated by current data. Stroke MRI holds the
      promise for an improved therapy by patient stratification and by opening the time
      window. Interventional recanalisation, vascular interventions and hemicraniectomy
      complement the therapeutic options in the acute phase of stroke.

PMID- 19838657
TI  - [Vasculitis and hereditary small vessel diseases].
AB  - In younger patients with stroke, cerebral vasculitis and hereditary small vessel
      diseases should be considered as important differential diagnoses. Since the
      clinical course of cerebral vasculitis is highly variable, diagnostic workup,
      which includes laboratory tests, CSF analysis, cranial magnetic resonance imaging
      and biopsy, is often challenging. Therapy should be initiated on an
      interdisciplinary basis and includes immunosuppressive induction and maintenance
      regimes. Hereditary small vessel diseases, e.g. CADASIL or Fabry's disease, can
      mimic clinical features of cerebral vasculitis. Their diagnosis which is based on
      family history, typical clinical features and genetic analysis often has
      implications for treatment and genetic counselling.

PMID- 19838658
TI  - [Female patient with type 2 diabetes in coma with metabolic acidosis].
AB  - In case of impaired consciousness, metabolic acidosis with wide anion gap and
      elevated lactate levels a metformin associated lactic acidosis should be
      considered in diabetic patients. Taking into account the contraindications to
      metformin, lactic acidosis is a rare complication, however - if it occurs - fatal
      in 50-80%. The outcome of the surviving patients is good, once the acute stage is
      outlived due to immediate hemofiltration.

PMID- 19838659
TI  - alpha- and beta-Adducin polymorphisms affect podocyte proteins and proteinuria in
      rodents and decline of renal function in human IgA nephropathy.
AB  - Adducins are cytoskeletal actin-binding proteins (alpha, beta, gamma) that
      function as heterodimers and heterotetramers and are encoded by distinct genes.
      Experimental and clinical evidence implicates alpha- and beta-adducin variants in
      hypertension and renal dysfunction. Here, we have addressed the role of alpha-
      and beta-adducin on glomerular function and disease using beta-adducin null mice,
      congenic substrains for alpha- and beta-adducin from the Milan hypertensive (MHS)
      and Milan normotensive (MNS) rats and patients with IgA nephropathy. Targeted
      deletion of beta-adducin in mice reduced urinary protein excretion, preceded by
      an increase of podocyte protein expression (phospho-nephrin, synaptopodin, alpha
      actinin, ZO-1, Fyn). The introgression of polymorphic MHS beta-adducin locus into
      MNS (Add2, 529R) rats was associated with an early reduction of podocyte protein
      expression (nephrin, synaptopodin, alpha-actinin, ZO-1, podocin, Fyn), followed
      by severe glomerular and interstitial lesions and increased urinary protein
      excretion. These alterations were markedly attenuated when the polymorphic MHS
      alpha-adducin locus was also present (Add1, 316Y). In patients with IgA
      nephropathy, the rate of decline of renal function over time was associated to
      polymorphic beta-adducin (ADD2, 1797T, rs4984) with a significant interaction
      with alpha-adducin (ADD1, 460W, rs4961). These findings suggest that adducin
      genetic variants participate in the development of glomerular lesions by
      modulating the expression of specific podocyte proteins.

PMID- 19838660
TI  - [Prophylactic ventilation of severely injured patients with thoracic trauma--does
      it always make sense?].
AB  - For therapy of blunt thoracic trauma in multiple injured patients, some studies
      have recommended prophylactic ventilation with kinetic therapy for 3-5 days. In
      contrast other clinics prefer to reduce the time of ventilation and to extubate
      as soon as possible. In this retrospective study our patient collective was
      investigated to find out if early extubation is linked to a higher complication
      rate. A total of 26 ventilated patients with severe thoracic trauma and an
      abbreviated injury scale score (AIS thorax) >3 were included in the study. The
      mean time of ventilation was 98.4 h and in patients without head injury 71.3 h.
      Out of 22 patients 4 had to be reintubated which had to be repeated for 2
      patients. Of the patients 3 developed pneumonia but no cases of adult respiratory
      distress syndrome (ARDS) were observed. Of the patients 4 died due to other
      injuries. The mean stay on the intensive care unit was 6.3 days and the mean stay
      in hospital 22.6 days. Our findings indicate that even with early and aggressive
      weaning from a respirator with extensive lung contusions an adequate therapy of
      thorax trauma is possible without having a higher incidence of complications.

PMID- 19838661
TI  - [Psychological factors related to gastric banding. Results of a follow-up study].
AB  - BACKGROUND: Obesity is a widespread illness in Western industrialized countries,
      causing a high financial burden for the health systems. Several studies could
      demonstrate the positive effects of bariatric surgery on psychological and
      psychosocial parameters. PATIENTS AND METHODS: Twenty patients with morbid
      obesity (BMI > or =40 kg/m(2)) answered two questionnaires, the SCL-90-R,
      assessing psychological distress, and the IIP-D, measuring interpersonal
      problems, before and 6 months after gastric banding. Six months after surgery an
      additional questionnaire measuring subjective feelings was administered, too.
      RESULTS: Seventy-five percent of the patients were dissatisfied with therapy and
      outcome. They reported a lack of psychological support as well as new surgery
      related physical and psychological symptoms. CONCLUSION: This study pointed out
      the necessity for psychotherapeutic help after surgery to manage already existing
      or new psychological needs due to gastric banding.

PMID- 19838663
TI  - [Addiction across the lifespan].
AB  - Alcohol and nicotine are with us during most of our lifetime. About 4,000
      children with fetal alcohol syndrome and another 20,000 children with fetal
      alcohol effects are born per year in Germany. Alcohol contributes to accidents
      and suicides especially in young people. It is particularly toxic for the
      developing brain.Germany is among the countries with a high consumption of
      alcohol and nicotine. Consequently substance-related diseases are highly
      prevalent. In the group of people aged 65 and older we expect a doubling of
      alcohol problems within the next 10 years. This will also lead to a sharp
      increase in alcohol-related dementias. Overall, treatment is effective especially
      if one considers the chronic relapsing nature of the disorder. Unfortunately,
      less than 10% of patients really receive specialist care. This segment needs to
      be expanded especially by psychiatrists and psychotherapists. Different
      prevention strategies are being applied but there is a reluctance to use a ban or
      curtail advertising and to raise taxes for a reduction in overall consumption.

PMID- 19838664
TI  - [Equal access to medical services over the lifespan].
AB  - Demand for health services is in principle unlimited, in contrast to resources.
      People covered by public health funds in principle have equal access to treatment
      according to the highest level of medical evidence available. In order to
      restrict expenditure the legislator stipulates different instruments. These
      include reference pricing for generics as well as price capping. The legislator
      still shies from price fixing which is well established in other states. Instead,
      office-based physicians are confronted by law with rationing decisions concerning
      their own services as well as services prescribed where the mentally ill are at
      special risk of becoming victims of intransparency, as exemplified by the
      heterogeneity of the prescription of psychotropic drugs. A systematic
      prioritization approach following internationally available models might open new
      perspectives.

PMID- 19838662
TI  - [Vaccination and multiple sclerosis].
AB  - Vaccinations to prevent communicable diseases are, like in other chronic
      diseases, of special importance in patients with multiple sclerosis (MS). Various
      bacterial and viral infections have been shown to induce relapses of MS. Reports
      of possible adverse effects of vaccinations on the course of multiple sclerosis
      have led patients and treating physicians to exercise caution in the use of
      vaccines. A number of vaccines have been studied with respect to the risk in MS
      patients. Some vaccines, for example against yellow fever, are not indicated in
      MS due to the risk of MS exacerbation. In contrast, tetanus or hepatitis B
      vaccines do not represent a risk for manifestation or disease progression of MS.
      Before and during immunomodulatory therapy of MS special attention should be
      given to adequate protection against vaccine preventable diseases.This paper
      reviews the indications and specific side effects of vaccinations in MS patients.
      Additionally, issues of vaccination under immunomodulatory therapy of MS are
      discussed.

PMID- 19838665
TI  - No evidence of increased risk of malignancies in patients with diabetes treated
      with insulin detemir: a meta-analysis.
AB  - AIMS/HYPOTHESIS: Recent epidemiological studies suggest that treatment with
      insulin glargine (A21Gly,B31Arg,B32Arg human insulin) may promote cancer growth.
      The present meta-analysis was performed to assess the risk of cancer during
      treatment with insulin detemir (B29Lys(epsilon-tetradecanoyl),desB30 human
      insulin), another long-acting insulin analogue. METHODS: This meta-analysis was
      performed in a population of 8,693 patients with type 1 or type 2 diabetes, who
      were included in Novo Nordisk-sponsored, randomised and controlled diabetes
      trials of at least 12 weeks in duration that compared insulin detemir with NPH
      insulin or insulin glargine. In a blinded manner, the adverse events with
      suspected treatment-emergent malignant tumours were obtained from these studies
      under three system-organ classes: 'Neoplasms benign, malignant and unspecified
      (including cysts and polyps)', 'Neoplasm' and 'Surgical and medical procedures'.
      Conditional ORs were estimated applying both the Mantel-Haenzel and Peto methods
      to ensure robustness of results. RESULTS: Separate analyses were performed for
      trials comparing insulin detemir with NPH insulin and insulin detemir with
      insulin glargine. In the first analysis, 16 studies were included with a total of
      3,983 patients treated with insulin detemir and 2,661 patients treated with NPH
      insulin. In the second analysis, five studies were included with a total of 1,219
      patients treated with insulin detemir and 830 patients treated with insulin
      glargine. The estimated OR for a cancer diagnosis between NPH insulin and insulin
      detemir was statistically significantly >1, with the ratio favouring insulin
      detemir. There was a more than twofold higher cancer occurrence in the NPH
      insulin-treated population. For the insulin detemir comparison with insulin
      glargine, there was a non-significant difference in ORs in favour of insulin
      detemir. CONCLUSIONS/INTERPRETATION: In these randomised controlled diabetes
      trials, patients treated with insulin detemir had a lower or similar occurrence
      of a cancer diagnosis compared with patients treated with NPH insulin or insulin
      glargine, respectively.

PMID- 19838666
TI  - [Acetabular revision surgery with the oblong revision cup : clinical and
      radiological results of 217 cases].
AB  - BACKGROUND: Deficiencies of the acetabular bone stock are an increasing and
      challenging problem in revision hip surgery. The LOR oblong revision cup is a
      valuable option in revision hip surgery. The purpose of this study was to assess
      outcomes with the LOR revision cup in hips with acetabular bone deficiency,
      analyze the complications, and identify predictors of survival rate. PATIENTS AND
      METHODS: From 1996 to 2002, 217 revision surgeries were performed with LOR cups.
      The mean patient age at operation was 67.5 years (range 29-87 years). The mean
      postoperative follow-up was 4 years (range 4-100 months). The patients were
      evaluated clinically and with the Harris hip score (HHS), UCLA score, and WOMAC
      index. A continuous radiographic assessment was done to detect heterotopic
      ossifications and radiolucencies or loosening on the basis of the Mayo hip score.
      Predictors of survival rate were estimated using Kaplan-Meier survivorship
      analysis. RESULTS: Twenty-four patients (7.4%) died during the study period.
      Seven patients (3.1%) had revisions because of aseptic loosening and two patients
      (0.9%) because of infection. Clinical assessment at follow-up showed a
      significantly improved mean HHS from 45 points preoperatively to 78 points
      postoperatively. At the most recent follow-up, patients with a body mass index
      below 30 or those classified as Charnley A had a significantly better HHS.
      Because of migration on the latest radiographs, revision was indicated in 4.8% of
      the cases. The survival rate of all LOR implants based on implant removal was 96%
      after 40 months and 87% after 80 months. Based on radiographic evidence of
      loosened implants, the survival rate was 94% after 40 months and 79% after 80
      months. Patients with more than two revisions had reduced implant survivorship
      compared with those having one or two revisions. The factors "age at operation",
      "gender", "obesity", "ASA score", "Charnley score", and "activity according to
      the UCLA score" did not influence the survival rate. CONCLUSION: We recommend
      this component in revision surgery on the basis of satisfactory clinical and
      radiological results at a mean of 48 months of follow-up. We identified the
      number of revisions as a predictor of survival rate.

PMID- 19838667
TI  - [Bone tissue engineering in clinical application : assessment of the current
      situation].
AB  - Treatment of severe bone defects remains a challenge in orthopaedic surgery and
      traumatology. Surgical techniques should provide primary stability to reach
      osseous integration and secondary remodeling of bone grafts and substitute
      materials. None of the currently available substitute materials provides
      osteoconduction and osteogenesis comparable to those of human allografts and
      autografts. To enhance osteoinductive and osteogenetic properties of these
      implants mesenchymal stem cells are used successfully in bone tissue engineering
      approaches. The aim of this report is to summarize the currently available data
      on bone tissue engineering and preliminary experience with a tissue engineered
      graft in acetabular revision surgery after loosening of a hip replacement.

PMID- 19838668
TI  - [In vitro trials with single and co-cultures of osteoblasts and endothelial cells
      : evaluation of new biomaterials for bone reconstruction and regeneration].
AB  - Many different types of bone substitute biomaterials are being developed for
      different applications in the body. The current dogma is that if osteoblasts and
      endothelial cells grow and exhibit normal cell functions on these materials in
      vitro as single cultures or in co-cultures, then the biomaterials are suitable
      for implantation for bone reconstruction and regeneration. Generally, only in
      vivo animal studies will prove whether this is the case. However, in vitro
      studies offer a good pre-screening and selection basis to evaluate the
      biocompatibility of novel biomaterials prior to animal studies. Multicell type co
      culture systems hold a great promise for the future.

PMID- 19838669
TI  - Secondary decline of cerebral autoregulation is associated with worse outcome
      after intracerebral hemorrhage.
AB  - PURPOSE: Blood pressure management in acute intracerebral hemorrhage (ICH) relies
      on functioning cerebral autoregulation. The time course of autoregulation in
      acute ICH and its relation with clinical outcome are not known. METHODS: Twenty
      six patients with spontaneous ICH were studied on days 1, 3 and 5 after ictus.
      Autoregulation was noninvasively measured from spontaneous fluctuations of blood
      pressure and middle cerebral artery flow velocity (assessed by transcranial
      Doppler) using the correlation coefficient index Mx. From the same signals, non
      invasive cerebral perfusion pressure was calculated. Results were compared with
      55 healthy controls and related with clinical and radiological factors and 90-day
      outcome (modified Rankin scale). RESULTS: Average Mx values of all patients did
      not differ across days or from controls. Higher Mx (i.e., poorer autoregulation)
      on day 5 was significantly related with lower Glasgow coma score, ventricular
      hemorrhage (both sides) and lower noninvasive cerebral perfusion pressure
      (ipsilateral). Increasing ipsilateral Mx between days 3 and 5 was related with
      lower Glasgow coma score and ventricular hemorrhage. In a multivariate analysis
      controlling for other hemodynamic factors, higher ipsilateral Mx on day 5 (p =
      0.013) was a significant predictor for poor 90-day outcome. CONCLUSIONS: Cerebral
      autoregulation is primarily preserved in acute ICH, but a secondary decline
      mainly ipsilateral to the ICH can occur. This is associated with poor clinical
      status, ventricular hemorrhage, lower cerebral perfusion pressure and worse
      clinical outcome.

PMID- 19838670
TI  - Free hamstrings tendon transfer and interference screw fixation for less invasive
      reconstruction of chronic avulsions of the Achilles tendon.
AB  - Reconstruction of chronic avulsions of the Achilles tendon can be technically
      difficult, as the calcaneus can be totally denuded of tendon, or only a small
      tuft of frayed tissue may have remain attached to the calcaneus, and be
      inadequate to allow a direct repair. In these patients, if it is not possible to
      directly reattach the Achilles tendon, a tendon graft can be necessary. We
      developed a less invasive technique using a free semitendinosus tendon graft with
      interference screw fixation in the calcaneus through a Cincinnati incision. Using
      this approach, a wide exposure of the insertion of the Achilles tendon is
      possible, preserving the integrity of the skin overlying the site most prone to
      wound breakdown.

PMID- 19838671
TI  - Simultaneous surgical management of chronic grade-2 valgus instability of the
      knee and anterior cruciate ligament deficiency in athletes.
AB  - We report on 22 patients with chronic grade-2 valgus laxity of the knee combined
      with chronic anterior cruciate ligament (ACL) insufficiency, in whom the two
      lesions were addressed at the same surgical setting. At a minimum follow-up of 24
      months, clinical and functional variables had improved significantly (P < 0.001),
      and 20 of the 22 patients (91%) had returned to sport at pre-injury level. There
      were no operative complications in this series. In selected athletes with chronic
      symptomatic valgus laxity of the knee combined with ACL insufficiency, surgical
      repair of the MCL in association with ACL reconstruction is a suitable and
      reliable option to restore knee stability and allow return to pre-injury activity
      level.

PMID- 19838672
TI  - Early versus delayed surgery for anterior cruciate ligament reconstruction: a
      systematic review and meta-analysis.
AB  - There is no consensus in the literature regarding the optimal timing of surgical
      reconstruction of the ruptured anterior cruciate ligament (ACL). Previous authors
      have suggested that early reconstruction may facilitate an early return to work
      or sport but may increase the incidence of post-operative complications such as
      arthrofibrosis. This study systematically reviewed the literature to determine
      whether ACL reconstruction should be performed acutely following rupture.
      Medline, CINAHL, AMED, EMBASE databases and grey literature were reviewed with a
      meta-analysis of pooled mean differences where appropriate. Six papers including
      370 ACL reconstructions were included. Early ACL reconstructions were considered
      as those undertaken within a mean of 3 weeks post-injury; delayed ACL
      reconstructions were those undertaken a minimum of 6 weeks post-injury. We found
      there was no difference in clinical outcome between patients who underwent early
      compared to delayed ACL reconstruction. However, this conclusion is based on the
      current literature which has substantial methodological limitations.

PMID- 19838673
TI  - Impact of monopolar radiofrequency energy on subchondral bone viability.
AB  - The purpose of this study was to analyze the impact of monopolar radiofrequency
      energy treatment on subchondral bone viability. The femoral grooves of six
      chinchilla bastard rabbits were exposed bilaterally to monopolar radiofrequency
      energy for 2, 4 and 8 s, creating a total of 36 defects. An intravital
      fluorescence bone-labeling technique characterized the process of subchondral
      bone mineralization within the 3 months following exposure to radiofrequency
      energy and was analyzed by widefield epifluorescence optical sectioning
      microscopy using an ApoTome. After 2 s of radiofrequency energy exposure, regular
      fluorescence staining of the subchondral bone was evident in all samples when
      compared to untreated areas. The depth of osteonecrosis after 4 and 8 s of
      radiofrequency energy treatment averaged 126 and 942 microm at 22 days (P < .05;
      P < .01). The 4 s treatment group showed no osteonecrosis after 44 days whereas
      the depth of osteonecrosis extended from 519 microm at 44 days (P < .01), to 281
      microm at 66 days (P < .01) and to 133 microm at 88 days (P < .05) after 8 s of
      radiofrequency energy application. Though radiofrequency energy may induce
      transient osteonecrosis in the superficial zone of the subchondral bone, the
      results of this study suggest that post-arthroscopic osteonecrosis appears to be
      of only modest risk given the current clinical application in humans.

PMID- 19838674
TI  - Accuracy of image-free navigation for severely deformed knees.
AB  - This study evaluated the accuracy of an image-free navigated total knee
      arthroplasty (TKA) system when used to align deformed tibia bone models. The
      accuracy was assessed in normal, 10 degrees varus, 20 degrees varus, 10 degrees
      valgus, and 20 degrees valgus tibia bone models (a total of five tibial models)
      by direct measurement of the navigated cutting guide. The mean angular errors in
      the tibial mechanical axes of the normal, 10 degrees, and 20 degrees varus
      models, respectively, were 0.0 degree, 0.7 degree varus, and 2.4 degrees varus.
      Thus, the errors seen with the two varus models were significantly larger than
      that associated with the normal model. The mean angular errors were 0.1 degree
      varus and 0.4 degree valgus in the 10 degrees and 20 degrees valgus models,
      respectively. These errors were not significantly different from those obtained
      with the normal model. These results suggest that in varus-deformed knees, image
      free navigation has a tendency to cut the tibia in varus. This fact is considered
      to be one of the reasons for the lack of superiority of TKA alignment in severely
      deformed knees when using image-free navigation. Therefore, special attention
      must be paid when using image-free navigation TKA in such cases.

PMID- 19838675
TI  - RC-QOL score for rotator cuff pathology: adaptation to Italian.
AB  - We translated and adapted the English RC-QOL (rotator cuff quality of life)
      questionnaire into Italian and performed reliability and validity evaluations of
      the Italian RC-QOL version in patients with rotator cuff tears. The RC-QOL
      English version was translated into Italian by a bilingual orthopaedic surgeon.
      The back translation of the Italian version into English was performed by another
      bilingual orthopaedic surgeon. The original version was compared with the back
      translation. The RC-QOL questionnaire was then administered to 22 subjects (range
      45-74 years) with a diagnosis of rotator cuff tears. For test-retest evaluation,
      the 22 patients were asked to complete the questionnaire at first examination,
      and 30 min following the end of this examination. The intraclass correlation
      coefficient for the 22 patients was 0.94 (95% CI = 0.85-0.98), indicating a high
      reliability. There were no significant differences between the scores immediately
      after the consultation and 30 min later. The Italian and the English versions of
      the RC-QOL questionnaire evaluate the same aspects of clinical severity in
      patients with rotator cuff tears.

PMID- 19838676
TI  - Platelet-rich plasma: intra-articular knee injections produced favorable results
      on degenerative cartilage lesions.
AB  - Platelet-rich plasma (PRP) is a natural concentrate of autologous blood growth
      factors experimented in different fields of medicine in order to test its
      potential to enhance tissue regeneration. The aim of our study is to explore this
      novel approach to treat degenerative lesions of articular cartilage of the knee.
      One hundred consecutive patients, affected by chronic degenerative condition of
      the knee, were treated with PRP intra-articular injections (115 knees treated).
      The procedure consisted of 150-ml of venous blood collected and twice
      centrifugated: 3 PRP units of 5 ml each were used for the injections. Patients
      were clinically prospectively evaluated before and at the end of the treatment,
      and at 6 and 12 months follow-up. IKDC, objective and subjective, and EQ VAS were
      used for clinical evaluation. Statistical analysis was performed to evaluate the
      significance of sex, age, grade of OA and BMI. A statistically significant
      improvement of all clinical scores was obtained from the basal evaluation to the
      end of the therapy and at 6-12 months follow-up (P < 0.0005). The results
      remained stable from the end of the therapy to 6 months follow up, whereas they
      became significantly worse at 12 months follow up (P = 0.02), even if still
      significantly higher respect to the basal level (P < 0.0005). The preliminary
      results indicate that the treatment with PRP injections is safe and has the
      potential to reduce pain and improve knee function and quality of live in younger
      patients with low degree of articular degeneration.

PMID- 19838677
TI  - Influence of SLAP lesions on chondral lesions of the glenohumeral joint.
AB  - From 2004 to 2008 we evaluated 431 SLAP lesions during 3,395 shoulder
      arthroscopies and compared two groups of patients, one with SLAP lesion as group
      I and one without SLAP lesions as group II. Exclusion of type I SLAP lesions,
      rotator cuff tears and history of dislocation of the shoulder in both groups left
      182 cases in group I, and additionally, exclusion of all-type SLAP lesions left
      251 patients in group II. In group I, SLAP lesion-associated chondral lesions
      were present in 20% at the humerus (4% group II, p = 0.005), 18% at the glenoid
      (5% in group II, p = 0.05) and 14% glenohumeral (3% group II, p = 0.04). We
      observed a pattern of typical localization of SLAP-associated chondral lesions at
      the humerus underneath the biceps tendon (78%) and at the anterior half of the
      glenoid (63%) in group I in contrast to the central region of the humerus (82%)
      and the central region at the glenoid (55%) in group II. The association of SLAP
      and chondral lesions was not influenced by the presence of trauma or age of the
      patients. SLAP lesions seem to be a risk factor for subsequent early onset of
      osteoarthritis either caused by a bicipital chondral print or glenohumeral
      instability or a combination of both.

PMID- 19838678
TI  - Interaction of sortase A and lipase 2 in the inhibition of Staphylococcus aureus
      biofilm formation.
AB  - Recombinant sortase A (SrtA) was used to immune rabbit, and the inhibitory
      activity of anti-SrtA serum on Staphylococcus aureus biofilm formation was
      tested. Biofilm formation was inhibited by anti-SrtA rabbit serum in S. aureus
      ATCC25923 and two clinical isolated strains. The antiserum was separated into two
      fractions, and the main component with the inhibitory activity was demonstrated
      to be the IgG fraction. Two proteins interact with the IgG fraction were
      identified by using an in vitro pull-down assay and were confirmed to be lipase 2
      and gamma-hemolysin by mass spectrometry. Cross-interaction between SrtA and
      lipase 2 was further confirmed by Western blotting. Addition of anti-lipase 2
      serum in the culture medium also showed inhibitory effect against biofilm
      formation. Together, our study suggests anti-SrtA serum inhibits S. aureus
      biofilm formation and lipase 2 is one of the targets of anti-SrtA serum in this
      inhibition process. This is the first study to demonstrate the roles of antisera
      against SrtA and lipase 2 in the inhibition of biofilm formation in S. aureus.

PMID- 19838679
TI  - Anaerobic metabolism of phenol in proteobacteria and further studies of
      phenylphosphate carboxylase.
AB  - Anaerobic phenol metabolism was studied in three facultative aerobic denitrifying
      bacteria, Thauera aromatica, "Aromatoleum aromaticum" strain EbN1
      (Betaproteobacteria), and Magnetospirillum sp. (Alphaproteobacterium). All
      species formed phenylphosphate and contained phenylphosphate carboxylase but not
      phenol carboxylase activity. This is in contrast to direct phenol carboxylation
      by fermenting bacteria. Antisera raised against subunits of the Thauera
      phenylphosphate synthase and phenylphosphate carboxylase partly cross-reacted
      with the corresponding proteins in the other species. Some unsolved features of
      phenylphosphate carboxylase were addressed in T. aromatica. The core sub-complex
      of this enzyme consists of three different subunits and catalyzes the exchange of
      (14)CO(2) with the carboxyl group of 4-hydroxybenzoate, but not phenylphosphate
      carboxylation. It was inactivated by oxygen or by the oxidizing agent thionin and
      fully reactivated under reducing conditions. The purified recombinant phosphatase
      subunit alone had only low phenylphosphate phosphatase activity in the absence of
      the other components. However, activity was strongly enhanced in the presence of
      the core enzyme resulting in phenylphosphate carboxylation. Hence, a tight
      interaction of the carboxylase subunits is required for dephosphorylation of
      phenylphosphate, which is coupled to the concomitant carboxylation of the
      produced phenolate to 4-hydroxybenzoate, thus preventing a futile cycle.

PMID- 19838680
TI  - Interference of the noradrenergic neurotoxin DSP4 with neuronal and nonneuronal
      monoamine transporters.
AB  - The haloalkylamine DSP4 (N[-2-chloroethyl]-N-ethyl-2-bromobenzylamine) is a
      noradrenergic neurotoxin, which is used for the chemical denervation of
      noradrenergic neurons, and it has been proposed to be a selective substrate for
      the neuronal, Na(+)- and Cl(-)-dependent noradrenaline transporter (NAT). In the
      present study, we investigated whether DSP4 not only interacts with the human NAT
      (hNAT) but also with other neuronal monoamine transporters such as the
      transporters for dopamine (hDAT) and serotonin (hSERT) or with nonneuronal (Na(+)
      independent) monoamine transporters also known as organic cation transporters
      (OCTs), such as hOCT(1), hOCT(2), and hOCT(3). Using human embryonic kidney
      HEK293 cells heterologously expressing the corresponding transporter, we show
      that DSP4 irreversibly inhibits the hNAT, hDAT, hSERT, and hOCT(3). However, this
      inhibition includes a reversible component at the hDAT, hSERT, and hOCT(3) but
      not at the hNAT. The inhibitory potency of DSP4 at the neuronal transporters was
      highest at the hNAT (IC(50) about 5 microM), and it was about five and 40 times
      lower at the hSERT and hDAT, respectively. DSP4 inhibited all three hOCTs with
      high potency (IC(50) about 1 microM) but in a completely reversible manner at
      hOCT(1) and hOCT(2). Cytotoxicity by 24-h exposure of hNAT- or hOCT-expressing
      cells to low DSP4 concentrations (<10 microM) could be observed only in hNAT
      expressing cells. Thus, DSP4's high-affinity uptake through the NAT together with
      its completely irreversible mode of interaction with the NAT may contribute to
      its selectivity as noradrenergic neurotoxin.

PMID- 19838681
TI  - Coupled thermogravimetry, mass spectrometry, and infrared spectroscopy for
      quantification of surface functionality on single-walled carbon nanotubes.
AB  - We have successfully applied coupled thermogravimetry, mass spectrometry, and
      infrared spectroscopy to the quantification of surface functional groups on
      single-walled carbon nanotubes. A high-purity single-walled carbon nanotube
      sample was subjected to a rapid functionalization reaction that attached butyric
      acid moieties to the nanotube sidewalls. This sample was then subjected to
      thermal analysis under inert desorption conditions. Resultant infrared and mass
      spectrometric data were easily utilized to identify the desorption of the butyric
      acid groups across a narrow temperature range and we were able to calculate the
      degree of substitution of the attached acid groups within the nanotube backbone
      as 1.7 carbon atoms per hundred, in very good agreement with independent
      analytical measurements made by inductively coupled plasma optical emission
      spectrometry (ICP-OES). The thermal analysis technique was also able to discern
      the presence of secondary functional moieties on the nanotube samples that were
      not accessible by ICP-OES. This work demonstrates the potential of this technique
      for assessing the presence of multiple and diverse functional addends on the
      nanotube sidewalls, beyond just the principal groups targeted by the specific
      functionalization reaction.

PMID- 19838682
TI  - Relevance and use of capillary coatings in capillary electrophoresis-mass
      spectrometry.
AB  - Over the last two decades, coupled capillary electrophoresis (CE)-mass
      spectrometry (MS) has developed into a generally accepted technique with a wide
      applicability. A growing number of CE-MS applications make use of capillaries
      where the internal wall is modified with surface coating agents. In CE-MS,
      capillary coatings are used to prevent analyte adsorption and to provide
      appropriate conditions for CE-MS interfacing. This paper gives an overview of the
      various capillary coating strategies used in CE-MS. The main attention is devoted
      to the way coatings can contribute to a proper CE-MS operation. The foremost
      capillary coating methods are discussed with emphasis on their compatibility with
      MS detection. The role of capillary coatings in the control of the electroosmotic
      flow and the consequences for CE-MS coupling are treated. Subsequently, an
      overview of reported applications of CE-MS employing different coating principles
      is presented. Selected examples are given to illustrate the usefulness of the
      coatings and the overall applicability of the CE-MS systems. It is concluded that
      capillary coatings can enhance the performance and stability of CE-MS systems,
      yielding a highly valuable and reproducible analytical tool.

PMID- 19838683
TI  - Field-based ion generation from microscale emitters on natural and artificial
      objects for atmospheric pressure mass spectrometry.
AB  - Field-based ion generation is described for ambient mass spectrometry. The
      technique allows the analysis of endogenously expressed chemicals and exogenously
      applied compounds directly from the cuticle of live insects in real time.
      Cuticular hairs serve as electric field-enhancing structures and play a key role
      in ion generation. Artificial emitters such as graphite whiskers or sharp metal
      tips replicate this effect.

PMID- 19838684
TI  - Effects on feeding rate and biomarker responses of marine mussels experimentally
      exposed to propranolol and acetaminophen.
AB  - Environmental risk assessments of human pharmaceuticals and other 'emerging
      contaminants' should integrate both population-relevant endpoints and biomarkers
      of potential modes of action in a range of species. Adult Mytilus
      galloprovincialis were exposed to the beta-adrenergic receptor blocker
      propranolol or to the anti-inflammatory drug acetaminophen (paracetamol), both
      commonly used therapeutic drugs present in aquatic ecosystems. Mussels were
      exposed under semi-static conditions for 10 days to either acetaminophen (CAS
      number 103-90-2; mean measured concentrations 23 and 403 microg/L) or propranolol
      hydrochloride (CAS number 318-98-9; mean measured propranolol concentrations 11
      and 147 microg/L) at 15 +/- 1 degrees C sea water. Feeding rate was assessed as
      an indicator of general toxicity. For propranolol, the 10-day no-observed effect
      concentration ((feeding rate)NOEC) and lowest observed effect concentration
      ((feeding rate)LOEC) were 11 and 147 microg/L, respectively. For acetaminophen,
      feeding rate was increased at both 23 and 403 microg/L, suggesting a 10-day
      (feeding rate)NOEC of 403 microg/L. Primarily, phase I carboxylesterase (CbE),
      phase II glutathione S-transferase (GST) and the anti-oxidant catalase activities
      were evaluated in digestive gland. Gill GST and acetylcholinesterase (AChE)
      activities were also measured. Lipid peroxidation (LPO) levels were measured in
      both tissues to assess oxidative stress. Some enzymatic activities in liver were
      also reduced after propranolol exposure whilst acetaminophen enhanced them (CbE p
      < 0.05). Acetaminophen exposure significantly increased hepatic LPO levels and
      inhibited AChE activity in gill (10-day NOEC and LOEC of 23 and 403 microg/L,
      respectively), whereas propranolol (11 microg/L) enhanced gill GST.

PMID- 19838685
TI  - Characterization, stoichiometry, and stability of salivary protein-tannin
      complexes by ESI-MS and ESI-MS/MS.
AB  - Numerous protein-polyphenol interactions occur in biological and food domains
      particularly involving proline-rich proteins, which are representative of the
      intrinsically unstructured protein group (IUP). Noncovalent protein-ligand
      complexes are readily detected by electrospray ionization mass spectrometry (ESI
      MS), which also gives access to ligand binding stoichiometry. Surprisingly, the
      study of interactions between polyphenolic molecules and proteins is still an
      area where ESI-MS has poorly benefited, whereas it has been extensively applied
      to the detection of noncovalent complexes. Electrospray ionization mass
      spectrometry has been applied to the detection and the characterization of the
      complexes formed between tannins and a human salivary proline-rich protein (PRP),
      namely IB5. The study of the complex stability was achieved by low-energy
      collision-induced dissociation (CID) measurements, which are commonly implemented
      using triple quadrupole, hybrid quadrupole time-of-flight, or ion trap
      instruments. Complexes composed of IB5 bound to a model polyphenol EgCG have been
      detected by ESI-MS and further analyzed by MS/MS. Mild ESI interface conditions
      allowed us to observe intact noncovalent PRP-tannin complexes with
      stoichiometries ranging from 1:1 to 1:5. Thus, ESI-MS shows its efficiency for
      (1) the study of PRP-tannin interactions, (2) the determination of stoichiometry,
      and (3) the study of complex stability. We were able to establish unambiguously
      both their stoichiometries and their overall subunit architecture via tandem mass
      spectrometry and solution disruption experiments. Our results prove that IB5.EgCG
      complexes are maintained intact in the gas phase.

PMID- 19838686
TI  - Time-resolved confocal fluorescence microscopy of trinitrobenzene-responsive
      organic nanofibers.
AB  - Time-resolved confocal fluorescence microscopy is used to image and analyze
      quantitatively the influence of 1,3,5-trinitrobenzene on the fluorescence of
      organic nanofibers. These nanofibers are formed by self-assembly of 2,3
      didecyloxyanthracene in methanol or from solutions drop-casted onto glass
      surfaces. Amplification of the fluorescence quenching emerges in the nanofibers
      as compared to the constituting monomer thus leading to efficient detection of
      nanomolar concentrations of TNB. The emission of dry nanofibers on glass is also
      efficiently quenched by vapors of TNB.

PMID- 19838687
TI  - An integrated study for mapping the moisture distribution in an ancient damaged
      wall painting.
AB  - An integrated study of microclimate monitoring, IR thermography (IRT),
      gravimetric tests and portable unilateral nuclear magnetic resonance (NMR) was
      applied in the framework of planning emergency intervention on a very
      deteriorated wall painting in San Rocco church, Cornaredo (Milan, Italy). The IRT
      investigation supported by gravimetric tests showed that the worst damage, due to
      water infiltration, was localized on the wall painting of the northern wall.
      Unilateral NMR, a new non-destructive technique which measures the hydrogen
      signal of the moisture and that was applied directly to the wall, allowed a
      detailed map of the distribution of the moisture in the plaster underlying the
      wall panting to be obtained. With a proper calibration of the integral of the
      recorded signal with suitable specimens, each area of the map corresponded to an
      accurate amount of moisture. IRT, gravimetric tests and unilateral NMR applied to
      investigate the northern wall painting showed the presence of two wet areas
      separated by a dry area. The moisture found in the lower area was ascribed to the
      occurrence of rising damp at the bottom of the wall due to the slope of the
      garden soil towards the northern exterior. The moisture found in the upper area
      was ascribed to condensation phenomena associated with the presence of a
      considerable amount of soluble, hygroscopic salts. In the framework of this
      integrated study, IRT investigation and gravimetric methods validated portable
      unilateral NMR as a new analytical tool for measuring in situ and without any
      sampling of the distribution and amount of moisture in wall paintings.

PMID- 19838688
TI  - Structural characterization of beta-amyloid oligomer-aggregates by ion mobility
      mass spectrometry and electron spin resonance spectroscopy.
AB  - Formation and accumulation of fibrillar plaques and aggregates of beta-amyloid
      peptide (Abeta) in brain have been recognized as characteristics of Alzheimer's
      disease (AD). Oligomeric aggregates of Ass are considered critical intermediates
      leading to progressive neurodegeneration; however, molecular details of the
      oligomerization and aggregation pathway and the structures of Abeta-oligomers are
      hitherto unclear. Using an in vitro fibril formation procedure of Abeta(1-40),
      beta-amyloid aggregates were prepared and insoluble aggregates separated from
      soluble products by centrifugation. In this study, ion mobility mass spectrometry
      (IM-MS) was applied in combination with electron paramagnetic resonance
      spectroscopy (EPR) to the identification of the components of Abeta-oligomers,
      and to their structural and topographical characterization. The formation of
      Abeta-oligomers and aggregates was monitored by gel electrophoresis, and Abeta
      oligomer bands were identified by in-gel tryptic digestion and matrix-assisted
      laser desorption ionization-mass spectrometry (MALDI-MS) to consist predominantly
      of Abeta(1-40) peptide. First, ion mobility-MS studies of soluble Abeta
      aggregates prepared by incubation for 5 days were performed on a quadrupole time
      of-flight mass spectrometer and revealed (1) the presence of at least two
      different conformational states, and (2), the formation of Met-35 oxidized
      products. For estimation of the size of Abeta-aggregates using EPR spectroscopy,
      a modified Abeta(1-40) peptide containing an additional N-terminal cysteine
      residue was prepared, and a 3-(2-iodoacetamido)-2,2,5,5-tetramethyl-1
      pyrrolidinyloxy radical spin label derivative (IPSL) was coupled by S-alkylation.
      The EPR spectra of the spin-labeled Cys-Abeta(1-40) oligomers were matched with
      spectra simulations using a multi-component simulation strategy, resulting in
      complete agreement with the gel electrophoresis results.

PMID- 19838689
TI  - Clam shell repair from the brown ring disease: a study of the organic matrix
      using confocal Raman micro-spectrometry and WDS microprobe.
AB  - Since 1987, the Manila clam Ruditapes philippinarum has been regularly affected
      by the brown ring disease (BRD), an epizootic caused by the bacterium Vibrio
      tapetis. This disease is characterized by the development of a brown deposit on
      the inner face of valves. While most of the clams die from the BRD infection,
      some of them are able to recover by mineralizing a new repair shell layer, which
      covers the brown deposit by a process of encapsulation. The purpose of this work
      was to study the organic matrix of the shells of Manila clams in the inner shell
      layer before, during and after the brown deposit and during the shell repair
      process by confocal Raman micro-spectrometry and wavelength dispersive
      spectrometry (WDS) microprobe. In addition, the organic matrix of the repaired
      shell layer was extracted and quantified, by using standard biochemical shell
      matrix extractions protocols. The brown deposit exhibited high luminescence
      intensity in Raman spectra, and an increase of S, C, Sr (forming two peaks) and a
      decrease of Ca, Na concentrations (% w/w), using WDS microprobe mapping and cross
      sectional transects. The signature of these trace elements was similar to that
      recorded on periostracal lamina (% w/w). The high S concentration likely
      corresponds to the presence of a high amount of sulfated organic compounds.
      Interestingly, on cross-sectional transects, before the brown deposit, a thin
      layer of the shell showed also a high luminescence, which may suggest that this
      layer is modified by bacteria. After the brown deposit, at the beginning of the
      shell repair process, the luminescence and the S concentration remain high,
      before declining the level found in non-BRD-affected shells. Quantification of
      the organic matrix shows that the shell repair layer zone is significantly
      different from non-BRD-affected shell layer, in particular with a much higher
      amount of insoluble matrix.

PMID- 19838691
TI  - Ontogeny of midazolam glucuronidation in preterm infants.
AB  - PURPOSE: In preterm infants, the biotransformation of midazolam (M) to 1-OH
      midazolam (OHM) by cytochrome P450 3A4 (CYP3A4) is developmentally immature, but
      it is currently unknown whether the glucuronidation of OHM to 1-OH-midazolam
      glucuronide (OHMG) is also decreased. The aim of our study was to investigate the
      urinary excretion of midazolam and its metabolites OHM and OHMG in preterm
      neonates following the intravenous (IV) or oral (PO) administration of a single M
      dose. METHODS: Preterm infants (post-natal age 3-13 days, gestational age 26-34
      4/7 weeks) scheduled to undergo a stressful procedure received a 30-min IV
      infusion (n = 15) or a PO bolus dose (n= 7) of 0.1 mg/kg midazolam. The
      percentage of midazolam dose excreted in the urine as M, OHM and OHMG up to 6 h
      post-dose was determined. RESULTS: The median percentage of the midazolam dose
      excreted as M, OHM and OHMG in the urine during the 6-h interval after the IV
      infusion was 0.44% (range 0.02-1.39%), 0.04% (0.01-0.13%) and 1.57% (0.36-7.7%),
      respectively. After administration of the PO bolus dose, the median percentage of
      M, OHM and OHMG excreted in the urine was 0.11% (0.02-0.59%), 0.02% (0.00-0.10%)
      and 1.69% (0.58-7.31%), respectively. The proportion of the IV midazolam dose
      excreted as OHMG increased significantly with postconceptional age (r = 0.73, p <
      0.05). CONCLUSION: The glucuronidation of OHM appears immature in preterm infants
      less than 2 weeks of age. The observed increase in urinary excretion of OHMG with
      postconceptional age likely reflects the combined maturation of glucuronidation
      and renal function.

PMID- 19838692
TI  - Stronger association of drug-induced progressive multifocal leukoencephalopathy
      (PML) with biological immunomodulating agents.
AB  - AIM: The aim of the present study was to collect and compare cases of drug
      induced PML in order to contribute to the debate about the role of the underlying
      diseases and/or drug immunosuppression in PML occurrence. METHODS: We searched
      for drug-induced PML cases in two international spontaneous adverse drug reaction
      (ADR) report databases, FDA-AERS and WHO-VigiBase. From MEDLINE, we retrieved
      case reports and case series containing the MESH term "leukoencephalopathy,
      progressive multifocal/chemically induced". In order to assess the PML-drug
      relationship, we analysed drug-reaction pairs in terms of the patients'
      underlying diseases and co-suspected drugs. RESULTS: Overall, 214 cases in FDA
      AERS, 118 in WHO-VigiBase and 140 in MEDLINE were collected. Therapeutic groups
      more frequently involved in PML cases were monoclonal antibodies (MAbs),
      conventional immunosuppressive drugs and anti-HIV drugs. The most frequent
      underlying diseases were lymphoproliferative diseases (28%), autoimmune disorders
      (20%) and transplants (10%). MAbs were more often reported in cases where they
      were the only suspected drugs, whereas for the other therapeutic groups,
      concomitant drugs were reported. CONCLUSIONS: We found a strong relationship
      between PML and MAbs, especially when used in autoimmune diseases. PML is
      becoming a crucial issue of MAbs, since they can cause severe ADRs through the
      imbalance of the immune system. Based on these results, patients treated with
      MAbs should be carefully monitored for early signs and symptoms of PML.

PMID- 19838690
TI  - Spinal cord modularity: evolution, development, and optimization and the possible
      relevance to low back pain in man.

PMID- 19838693
TI  - Genome-wide association analysis of canine atopic dermatitis and identification
      of disease related SNPs.
AB  - In humans, genome-wide association studies (GWAS) have been shown to be an
      effective and thorough approach for identifying polymorphisms associated with
      disease phenotypes. Here, we describe the first study to perform a genome-wide
      association study in canine atopic dermatitis (cAD) using the Illumina Canine
      SNP20 array, containing 22,362 single-nucleotide polymorphisms (SNPs). The aim of
      the study was to identify SNPs associated with cAD using affected and unaffected
      Golden Retrievers. Further validation studies were performed for potentially
      associated SNPs using Sequenom genotyping of larger numbers of cases and controls
      across eight breeds (Boxer, German Shepherd Dog, Labrador, Golden Retriever,
      Shiba Inu, Shih Tzu, Pit Bull, and West Highland White Terriers). Using meta
      analysis, two SNPs were associated with cAD in all breeds tested. RS22114085 was
      identified as a susceptibility locus (p=0.00014, odds ratio=2) and RS23472497 as
      a protective locus (p=0.0015, odds ratio=0.6). Both of these SNPs were located in
      intergenic regions, and their effects have been demonstrated to be independent of
      each other, highlighting that further fine mapping and resequencing is required
      of these areas. Further, 12 SNPs were validated by Sequenom genotyping as
      associated with cAD, but these were not associated with all breeds. This study
      suggests that GWAS will be a useful approach for identifying genetic risk factors
      for cAD. Given the clinical heterogeneity within this condition and the
      likelihood that the relative genetic effect sizes are small, greater sample sizes
      and further studies will be required.

PMID- 19838695
TI  - Biodegradation of thiocyanate using co-culture of Klebsiella pneumoniae and
      Ralstonia sp.
AB  - Thiocyanate-degrading microbial co-culture was isolated from thiocyanate
      contaminated site and tested for thiocyanate degradation potential and
      thiocyanate-toxicity tolerance and identified as Klebsiella pneumoniae and
      Ralstonia sp. by 16S rDNA sequencing. The co-culture was able to degrade
      thiocyanate with degradation rate of 500 mg L(-1)d(-1) at 2,500 mg L(-1)
      thiocyanate concentration at pH 6.0 and 37 degrees C following thiocyanate
      hydrolase pathway. The Haldane kinetic model elucidates the growth and
      thiocyanate biodegradation kinetics of the co-culture with Ki value of 1,876 mg
      L(-1). The thiocyanate biodegradation kinetics was not affected by the additional
      supply of glucose. The very high activities of thiocyanate hydrolase, cyanide
      oxygenase, and cytochrome P-450 content during growth on thiocyanate were
      observed, showing the induction mechanism.

PMID- 19838694
TI  - Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503.
AB  - Residue 116 of major histocompatibility complex (MHC) class I heavy chains is an
      important determinant of assembly, that can influence rates of ER-Golgi
      trafficking, binding to the transporter associated with antigen processing (TAP),
      tapasin dependence of assembly, and the efficiency and specificity of peptide
      binding. Here, we investigated assembly and peptide-binding differences between
      HLA-B*3501(S116) and HLA-B*3503(F116), two alleles differing only at position 116
      of the MHC class I heavy chain, that are associated respectively with normal or
      rapid AIDS progression. A reduced intracellular maturation rate was observed for
      HLA-B*3503 in HIV-infected and uninfected cells, which correlated with enhanced
      binding of HLA-B*3503 to TAP. No significant differences in the intrinsic
      efficiency of in vitro peptide binding by HLA-B*3501 and HLA-B*3503 were
      measurable with several common peptides or peptide libraries, and both allotypes
      were relatively tapasin-independent for their assembly. However, thermostability
      differences between the two allotypes were measurable in a CD4(+) T cell line.
      These findings suggest that compared to HLA-B*3501, a reduced intracellular
      peptide repertoire for HLA-B*3503 could contribute to its slower intracellular
      trafficking and stronger association with rapid AIDS progression.

PMID- 19838696
TI  - Biosynthetic pathway of sugar nucleotides essential for welan gum production in
      Alcaligenes sp. CGMCC2428.
AB  - Welan gum is a microbial polysaccharide produced by Alcaligenes sp. CGMCC2428
      that has D-glucose, D-glucuronic acid, D-glucose, and L-rhamnose as the main
      structural unit. The biosynthetic pathway of sugar nucleotides essential for
      producing welan gum in this strain was established in the following ways: (1) the
      detection of the presence of several intermediates and key enzymes; (2) the
      analysis of the response upon addition of precursors to the culture medium; (3)
      the correlation of the activities between several key enzymes with the yields of
      welan gum. With addition of 200-microM glucose-6-phosphate and fructose-6
      phosphate, the production of welan gum was improved by 18%. The activities of
      phosphoglucomutase, phosphomannose isomerase, UDP-glucose pyrophosphorylase, and
      dTDP-glucose pyrophosphorylase, correlated well with the yields of welan gum.
      According to these findings, the biosynthetic pathway was proposed to involve the
      metabolism of glucose via two discrete systems. The first involves conversion of
      glucose to glucose-6-phosphate, with further reactions producing glucose-1
      phosphate and fructose-6-phosphate, which are metabolized to the nucleotide sugar
      precursors of welan gum. The second system involves metabolism of glucose to
      synthesize the basic structural skeleton of the cell via central metabolic
      pathways, including the Entner-Doudoroff pathway, the pentose phosphate pathway,
      and the tricarboxylic acid cycle.

PMID- 19838697
TI  - Sugar transporters in efficient utilization of mixed sugar substrates: current
      knowledge and outlook.
AB  - There is increasing interest in production of transportation fuels and commodity
      chemicals from lignocellulosic biomass, most desirably through biological
      fermentation. Considerable effort has been expended to develop efficient
      biocatalysts that convert sugars derived from lignocellulose directly to value
      added products. Glucose, the building block of cellulose, is the most suitable
      fermentation substrate for industrial microorganisms such as Escherichia coli,
      Corynebacterium glutamicum, and Saccharomyces cerevisiae. Other sugars including
      xylose, arabinose, mannose, and galactose that comprise hemicellulose are
      generally less efficient substrates in terms of productivity and yield. Although
      metabolic engineering including introduction of functional pentose-metabolizing
      pathways into pentose-incompetent microorganisms has provided steady progress in
      pentose utilization, further improvements in sugar mixture utilization by
      microorganisms is necessary. Among a variety of issues on utilization of sugar
      mixtures by the microorganisms, recent studies have started to reveal the
      importance of sugar transporters in microbial fermentation performance. In this
      article, we review current knowledge on diversity and functions of sugar
      transporters, especially those associated with pentose uptake in microorganisms.
      Subsequently, we review and discuss recent studies on engineering of sugar
      transport as a driving force for efficient bioconversion of sugar mixtures
      derived from lignocellulose.

PMID- 19838698
TI  - Stimulation of bikaverin production by sucrose and by salt starvation in Fusarium
      fujikuroi.
AB  - The fungus Fusarium fujikuroi (Gibberella fujikuroi mating group C) exhibits a
      rich secondary metabolism that includes the synthesis of compounds of
      biotechnological interest, such as gibberellins, bikaverin, and carotenoids. The
      effect of the carbon source on their production was checked using a two-phase
      incubation protocol, in which nine different sugars were added upon transfer of
      the fungus from repressed to appropriate inducing conditions, i.e., nitrogen
      starvation for gibberellins and bikaverin and illumination for carotenoids
      production. Most of the carbon sources allowed the synthesis of these metabolites
      in significant amounts. However, bikaverin production was strongly increased by
      the presence of sucrose in comparison to other carbon sources, an effect not
      exhibited for the production of gibberellins and carotenoids. The bikaverin
      inducing effect was enhanced in the absence of phosphate and/or sulfate. Similar
      results were also observed in carotenoid-overproducing strains known to be
      altered in bikaverin production. The induction by salt starvation, but not by
      sucrose, correlated with an increase in messenger RNA levels of gene bik1,
      encoding a polyketide synthase of the bikaverin pathway.

PMID- 19838699
TI  - Linking performance to microbiology in biofilters treating dimethyl sulphide in
      the presence and absence of methanol.
AB  - The performance and microbiology of two inorganic biofilters treating dimethyl
      sulphide (DMS) in the presence and absence of methanol was investigated. Addition
      of methanol was shown to result in an increase in DMS removal for methanol
      loadings below 90 g MeOH per cubic metre per hour with the optimal methanol
      loading around 10-15 g MeOH per cubic metre per hour for a DMS loading of 3.4 g
      DMS per cubic metre per hour, a fivefold increase in the DMS removal rate
      compared to the biofilter treating DMS alone. Microbial community analysis
      revealed that the addition of methanol led to a significant increase of up to an
      order of magnitude in the abundance of Hyphomicrobium spp. in the biofilter co
      treating DMS and methanol compared to the biofilter treating DMS alone, whilst
      there was no significant difference in the abundance of Thiobacillus spp. between
      the two biofilters. Given the behaviour of the biofilter co-treating DMS and
      methanol, the magnitude of the increase in Hyphomicrobium spp. in the biofilter
      co-treating DMS and methanol and the ability of Hyphomicrobium spp. to use both
      methanol and DMS as growth substrates, it was concluded that Hyphomicrobium spp.
      were the microorganisms responsible for the bulk of the DMS degradation in the
      biofilter co-treating DMS and methanol.

PMID- 19838700
TI  - FDG PET as a prognostic predictor in the early post-therapeutic evaluation for
      unresectable hepatocellular carcinoma.
AB  - PURPOSE: To elucidate the prognostic role of post-therapeutic (18)F
      fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET), we conducted a
      retrospective cohort study analysing the clinical factors that affect overall
      survival after non-operative therapy for unresectable hepatocellular carcinoma
      (HCC). METHODS: Sixty-seven cases with unresectable HCC who received non
      operative therapy (transcatheter arterial chemoembolization: n = 24,
      transcatheter arterial infusion chemotherapy: n = 31, radiofrequency ablation: n
      = 5 or systemic chemotherapy: n = 7) and had received FDG PET for the evaluation
      of the therapeutic effect within 1 month after the end of the therapy were
      evaluated. Overall survival rate was evaluated using the univariate and
      multivariate analyses of relevant clinical and laboratory parameters before and
      after therapy, including visual PET analysis and quantitative analysis using
      maximum standardized uptake value (SUV). RESULTS: Visual PET diagnosis of post
      therapeutic lesions was a good predictor of overall survival of unresectable HCC
      patients. The low FDG group showed significantly longer survival (average: 608
      days) than that (average: 328 days) of the high FDG group (p < 0.0001).
      Multivariate analysis showed four significant prognostic factors for the
      survival: post-therapeutic alpha-fetoprotein (alphaFP) level (=400 ng/ml, p =
      0.004), post-therapeutic visual PET diagnosis (p = 0.006), post-therapeutic
      clinical stage (UICC stage IV, p = 0.04) and post-therapeutic Milan criteria (p =
      0.03), while pre-therapeutic clinical factors, SUV by post-therapeutic FDG PET
      (5.0 or more) or others did not show significance. CONCLUSION: The present study
      suggests that post-therapeutic PET performed within 1 month after non-operative
      therapy can be a good predictor of overall survival in unresectable HCC patients,
      while pre-therapeutic evaluation including PET, tumour markers and clinical
      staging may not be useful.

PMID- 19838701
TI  - Imaging of EGFR expression in murine xenografts using site-specifically labelled
      anti-EGFR 111In-DOTA-Z EGFR:2377 Affibody molecule: aspect of the injected tracer
      amount.
AB  - INTRODUCTION: Overexpression of epidermal growth factor receptor (EGFR) is a
      prognostic and predictive biomarker in a number of malignant tumours.
      Radionuclide molecular imaging of EGFR expression in cancer could influence
      patient management. However, EGFR expression in normal tissues might complicate
      in vivo imaging. The aim of this study was to evaluate if optimization of the
      injected protein dose might improve imaging of EGFR expression in tumours using a
      novel EGFR-targeting protein, the DOTA-Z(EGFR:2377) Affibody molecule. METHODS:
      An anti-EGFR Affibody molecule, Z(EGFR:2377), was labelled with (111)In via the
      DOTA chelator site-specifically conjugated to a C-terminal cysteine. The affinity
      of DOTA-Z(EGFR:2377) for murine and human EGFR was measured by surface plasmon
      resonance. The cellular processing of (111)In-DOTA-Z(EGFR:2377) was evaluated in
      vitro. The biodistribution of radiolabelled Affibody molecules injected in a
      broad range of injected Affibody protein doses was evaluated in mice bearing EGFR
      expressing A431 xenografts. RESULTS: Site-specific coupling of DOTA provided a
      uniform conjugate possessing equal affinity for human and murine EGFR. The
      internalization of (111)In-DOTA-Z(EGFR:2377) by A431 cells was slow. In vivo, the
      conjugate accumulated specifically in xenografts and in EGFR-expressing tissues.
      The curve representing the dependence of tumour uptake on the injected Affibody
      protein dose was bell-shaped. The highest specific radioactivity (lowest injected
      protein dose) provided a suboptimal tumour-to-blood ratio. The results of the
      biodistribution study were confirmed by gamma-camera imaging. CONCLUSION: The
      (111)In-DOTA-Z(EGFR:2377) Affibody molecule is a promising tracer for
      radionuclide molecular imaging of EGFR expression in malignant tumours. Careful
      optimization of protein dose is required for high-contrast imaging of EGFR
      expression in vivo.

PMID- 19838702
TI  - EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled
      dopamine transporter ligands, version 2.
AB  - These guidelines summarize the current views of the European Association of
      Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to
      assist nuclear medicine practitioners when making recommendations, performing,
      interpreting, and reporting the results of clinical dopamine transporter (DAT)
      single photon emission computed tomography (SPECT) studies using (123)I-labelled
      radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT
      imaging, which will increase the diagnostic impact of this technique in
      neurological practice. The present document is an update of the 2002 guidelines
      [1] and has been guided by the views of various national societies: the Task
      Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a
      consensus statement of the imaging centres included in the "Kompetenznetz
      Parkinson" sponsored by the German Federal Ministry of Education, and the Task
      Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3].
      The guidelines reflect the individual experience of experts in European
      countries. The guidelines are intended to present information specifically
      adapted to European practice. The information provided should be taken in the
      context of local conditions and regulations.

PMID- 19838703
TI  - EANM procedure guideline for brain perfusion SPECT using 99mTc-labelled
      radiopharmaceuticals, version 2.
AB  - These guidelines summarize the current views of the European Association of
      Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is
      to assist nuclear medicine practitioners when making recommendations, performing,
      interpreting, and reporting the results of brain perfusion single photon emission
      computed tomography (SPECT) studies using (99m)Tc-labelled radiopharmaceuticals.
      The aim is to achieve a high quality standard for brain perfusion SPECT imaging,
      which will increase the diagnostic impact of this technique in clinical practice.
      The present document replaces a former version of the guideline published in 2001
      which was inspired by the Society of Nuclear Medicine Procedure Guideline for
      Brain Perfusion SPECT [1], the views of the Society of Nuclear Medicine Brain
      Imaging Council [2], and the individual experience of experts in European
      countries. The guidelines are intended to present information specifically
      adapted to European practice. The information provided should be taken in the
      context of local conditions and regulations.

PMID- 19838704
TI  - EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2
      receptor ligands, version 2.
AB  - The guidelines summarize the current views of the European Association of Nuclear
      Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist
      nuclear medicine practitioners in making recommendations, performing,
      interpreting and reporting the results of clinical dopamine D2 receptor SPECT or
      PET studies, and to achieve a high quality standard of dopamine D2 receptor
      imaging, which will increase the impact of this technique in neurological
      practice.The present document is an update of the first guidelines for SPECT
      using D2 receptor ligands labelled with (123)I [1] and was guided by the views of
      the Society of Nuclear Medicine Brain Imaging Council [2], and the individual
      experience of experts in European countries. The guidelines intend to present
      information specifically adapted to European practice. The information provided
      should be taken in the context of local conditions and regulations.

PMID- 19838705
TI  - EANM procedure guidelines for PET brain imaging using [18F]FDG, version 2.
AB  - These guidelines summarize the current views of the European Association of
      Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is
      to assist nuclear medicine practitioners in making recommendations, performing,
      interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose
      ([(18)F]FDG) PET imaging of the brain. The aim is to help achieve a high standard
      of FDG imaging, which will increase the diagnostic impact of this technique in
      neurological and psychiatric practice. The present document replaces a former
      version of the guidelines that were published in 2002 [1] and includes an update
      in the light of advances in PET technology, the introduction of hybrid PET/CT
      systems and the broadening clinical indications for FDG brain imaging. These
      guidelines are intended to present information specifically adapted for European
      practice. The information provided should be taken in the context of local
      conditions and regulations.

PMID- 19838706
TI  - Results of high tibial osteotomy: review of the literature.
AB  - The aim of this review is to evaluate long-term follow-up and survival analysis
      studies regarding high tibial osteotomies (HTO) for the treatment of medial knee
      arthritis. Despite the good number of studies available, comparison and pooling
      of the results are challenging because of the different evaluation systems and
      techniques used. However, in general, published studies on HTO report good long
      term results with a correct patient selection and a precise surgical technique.
      Based on our findings, the ideal candidate for an HTO is a young patient (<60
      years of age), with isolated medial osteoarthritis, with good range of motion and
      without ligamentous instability. Furthermore, the literature review shows that
      the outcomes gradually deteriorate with time. Nevertheless, some issues remain
      that need resolution; these include the choice between opening or closing wedge
      tibial osteotomy, the graft selection in opening wedge osteotomies, the type of
      fixation, the comparison with unicompartmental knee arthroplasty and whether HTO
      significantly affects a subsequent total joint replacement.

PMID- 19838707
TI  - Long-term clinical results of the Oxford medial unicompartmental knee
      arthroplasty.
AB  - The purposes of this study were to investigate the mode of failure and
      survivorship of an independently performed series of medial Oxford
      unicompartmental knee arthroplasties. The study included 43 knees in 40 patients
      with a mean follow-up of 14.88 years: 13 knees (11 patients) had revision surgery
      (30%), and ten patients required conversion to total knee prosthesis. The mean
      International Knee Society (IKS) scores at the time of the revision were 145.52
      [standard deviation (SD): 39.90, range: 167-200]. The overall alignment of the
      knee was restored to neutral, with a hip-knee-ankle (HKA) angle average of 178
      degrees  (SD: 3.21 degrees , range: 170-186 degrees ). Survivorship, as defined
      by an endpoint of failure for any reason, showed that the survival rate at five
      years was 90%, at ten years 74.7% and at 15 years 70%. Excluding inappropriate
      patient selection and surgeon-associated failures, our survival analysis plot is
      much improved: survivorship at five years is 94.5%, at ten years 85.7% and at 15
      years 80.4%. The Oxford meniscal bearing arthroplasty offers long-term pain
      relief with good knee function. Unfortunately, we demonstrated a high
      complication rate, with some of the failures encountered indicating that the
      surgical technique is very demanding.

PMID- 19838708
TI  - Prospective study of surgical delay for hip fractures: impact of an
      orthogeriatrician and increased trauma capacity.
AB  - Most health services in the United Kingdom provide unacceptable in-hospital care
      for hip fracture patients. We describe the impact on surgical delay following the
      introduction of an orthogeriatrician and the addition of one extra trauma list
      per week at our centre. Prospective data were collected on 101 consecutive
      patients followed by a second cohort of 105 patients. Mean time to surgery in
      cohorts 1 and 2 was 4.08 and 4.05 days, respectively (p = 0.71). Diagnosis of
      medical comorbidity increased with input from the orthogeriatrician from 69.7% to
      74.2% (p = 0.24). Length of stay and mortality were comparable in the two groups.
      A full trauma list accounted for the most frequent orthopaedic delay, which
      decreased from 18.1% to 12.9% (p = 0.09). Increased recognition of medical
      comorbidity has financial implications for hospital remuneration. However, lack
      of orthopaedic provisions accounts for significant avoidable surgical delay
      requiring further investment if national standards are to be achieved.

PMID- 19838709
TI  - Glutathione S-transferase gene deletions and their effect on iron status in
      HbE/beta thalassemia patients.
AB  - Iron overload and oxidative stress are main pathophysiological features of
      HbE/beta thalassemia patients. Glutathione S-transferase genes (GSTT1 and GSTM1)
      are well known detoxification agents, and any mutation in the gene is known to
      cause oxidative damage. This study was aimed to compare the prevalence of GST
      deletions in 240 HbE/beta thalassemia patients with 100 controls and to determine
      role of deletions on iron overload. We observed significantly higher frequency of
      GSTT1 (P = 0.001) and GSTT1/GSTM1 (P = 0.03) in comparison to controls. Patients
      who had null genotype for both the alleles, i.e., GSTT1/GSTM1 had significantly
      higher levels of serum iron (P = 0.007) and serum ferritin (P = 0.001) than
      patients with normal genotype for GST deletions. This is the first study to prove
      the role of GST gene deletions with iron overload in HbE/beta thalassemia.

PMID- 19838710
TI  - [Volume calculations for current intravitreal injections of Lucentis].
AB  - BACKGROUND: Medications for blocking vascular endothelial growth factor (VEGF)
      are currently used for therapy of neovascular age-related macular degeneration
      (AMD). Some users divide the original volume of the medication Lucentis into
      smaller aliquots to be used for several patients. The aim of this study was to
      investigate whether the current original aliquot volume of Lucentis can
      principally be subdivided to be used for treatment two patients each with a 0.05
      ml injection volume. MATERIALS AND METHODS: The calculation of the dead space
      volume of the vessels used for injection was carried out by weighing the empty
      and full weights using an analytical balance. The sum of all dead space volumes
      was subtracted from the filling volumes. Additionally, the average extractable
      volume was determined from 200 original aliquots of Lucentis. RESULTS: Taking all
      necessary dead space volumes into consideration it was calculated that an
      extractable volume of at least 0.137 ml is necessary in order to be able to
      inject the necessary volume of 0.05 ml of the solution containing the active
      ingredient. The original volume of 0.23 ml contained in an aliquot of Lucentis
      cannot therefore be divided among two patients. The average extractable volume of
      0.16 ml is clearly less than the full volume of 0.23 ml. CONCLUSIONS: The
      original aliquots of Lucentis contain a full volume of 0.23 ml and are not
      suitable to be used to treat two patients. The volume can only be divided among
      several patients if several original aliquots are pooled and refilled. This
      however, presupposes a renewed filling of aliquots which represents a new
      potential source of contamination. Also legal aspects and the question of
      stability of the active ingredient have not been taken into consideration.

PMID- 19838711
TI  - [Acute retinal necrosis from the virologist's perspective].
AB  - Acute retinal necrosis occurs in approximately one per million persons per year
      and is caused in approximately 70% of the cases by the varicella zoster virus or
      in about 30% of the cases by herpes simplex virus. The early diagnosis is
      primarily based on virus-specific polymerase chain reaction in fluid from the
      anterior chamber or vitreous humor and can be supported by the determination of
      specific antibody titers from fluid and serum. Virus detection provides the basis
      for early causative therapy which limits disease progression and risk of
      complications. Retinal infections by varicella zoster virus or herpes simplex
      virus are treated with aciclovir, ganciclovir, or famciclovir. Ganciclovir and
      valganciclovir are used for the therapy of retinal cytomegalovirus infections. In
      the case of resistance development, foscarnet or cidofovir are available as
      second line antiviral drugs. The early use of specific antiviral agents is a
      crucial prerequisite for optimized therapy of acute retinal necrosis.

PMID- 19838712
TI  - [Biometry in cataract camps. Experiences from north Kenya].
AB  - BACKGROUND: Biometry has the potential to improve refractive outcomes of cataract
      surgery in developing countries. However, the procedure is difficult to carry out
      in remote areas. PATIENTS AND METHODS: The feasibility of automated biometry
      using portable devices was assessed in an eye camp in a remote Kenyan community
      and reasons for failure were documented. PC-IOLs in the range of 17-27 dioptres
      (dpt) were implanted and a model was created to predict spherical refractive
      error if a standard 22 dpt lens had been used. RESULTS: In 104 out of 131 eyes
      (80%) biometry was possible. Failure to obtain K-readings in eyes with coexisting
      corneal pathology was the main limiting factor. The calculated mean IOL strength
      to achieve emmetropia was 21.56 dpt with a SD=1.96 (min: 14.78 dpt, max: 27.24
      dpt). If 22 dpt lenses had been implanted around 20% would have had an error of
      more than 2 dpt and 7% an error of more than 3 dpt. CONCLUSION: Biometry is a
      challenging procedure in remote areas where comorbidities are common. However,
      without biometry and implantation of different IOL powers poor refractive outcome
      can be expected in around 20% of patients.

PMID- 19838713
TI  - Acid-base regulatory ability of the cephalopod (Sepia officinalis) in response to
      environmental hypercapnia.
AB  - Acidification of ocean surface waters by anthropogenic carbon dioxide (CO(2))
      emissions is a currently developing scenario that warrants a broadening of
      research foci in the study of acid-base physiology. Recent studies working with
      environmentally relevant CO(2) levels, indicate that some echinoderms and
      molluscs reduce metabolic rates, soft tissue growth and calcification during
      hypercapnic exposure. In contrast to all prior invertebrate species studied so
      far, growth trials with the cuttlefish Sepia officinalis found no indication of
      reduced growth or calcification performance during long-term exposure to 0.6 kPa
      CO(2). It is hypothesized that the differing sensitivities to elevated seawater
      pCO(2) could be explained by taxa specific differences in acid-base regulatory
      capacity. In this study, we examined the acid-base regulatory ability of S.
      officinalis in vivo, using a specially modified cannulation technique as well as
      (31)P NMR spectroscopy. During acute exposure to 0.6 kPa CO(2), S. officinalis
      rapidly increased its blood [HCO(3)(-)] to 10.4 mM through active ion-transport
      processes, and partially compensated the hypercapnia induced respiratory
      acidosis. A minor decrease in intracellular pH (pH(i)) and stable intracellular
      phosphagen levels indicated efficient pH(i) regulation. We conclude that S.
      officinalis is not only an efficient acid-base regulator, but is also able to do
      so without disturbing metabolic equilibria in characteristic tissues or
      compromising aerobic capacities. The cuttlefish did not exhibit acute intolerance
      to hypercapnia that has been hypothesized for more active cephalopod species
      (squid). Even though blood pH (pHe) remained 0.18 pH units below control values,
      arterial O(2) saturation was not compromised in S. officinalis because of the
      comparatively lower pH sensitivity of oxygen binding to its blood pigment. This
      raises questions concerning the potentially broad range of sensitivity to changes
      in acid-base status amongst invertebrates, as well as to the underlying
      mechanistic origins. Further studies are needed to better characterize the
      connection between acid-base status and animal fitness in various marine species.

PMID- 19838714
TI  - [Familial clustering, genetic roots and insights into the pathogenesis of
      autoimmune diseases].
AB  - Genome-wide association studies have dramatically increased our knowledge about
      the genetic contribution to autoimmune diseases. The identified genes are
      indicators for signal transduction pathways involved in disease pathogenesis and
      could contribute to potential new therapeutic approaches.

PMID- 19838715
TI  - [Color Doppler sonography for investigation of peripheral joints and ligaments].
AB  - Doppler ultrasound is able to visualize blood flow by the change in frequency
      (Doppler shift) of sound waves which are reflected by moving blood cells inside
      the vessels (Doppler effect). As hyperemia caused by vasodilatation and
      angiogenesis is the earliest detectable pathologic change in the beginning of
      synovitis, Doppler ultrasonography can be used to assess inflammatory activity.
      Several studies could show a strong correlation between magnetic resonance
      imaging (MRI) as well as histological findings (blood vessel density) and Doppler
      sonographic determination of synovial perfusion. Equipment settings must be
      adapted to slow blood flow in very small blood vessels to reach an appropriate
      imaging quality. Color and power Doppler ultrasound can depict different grades
      of intra-articular and peritendinous blood flow, which allows an estimation of
      inflammatory activity and facilitates the differentiation and monitoring of
      rheumatic diseases during follow up.

PMID- 19838716
TI  - [Methotrexate in rheumatology].
AB  - Methotrexate (MTX) is a folate inhibitor which has gained a major role in the
      treatment of rheumatoid arthritis (RA). MTX is not only the disease modifying
      anti-rheumatic drug of first choice, a large number of clinical trials moreover
      show that biologic drugs should be combined with MTX in order to obtain optimal
      therapeutic efficacy. Therefore, MTX is an anchor drug for the treatment of RA.
      Large studies show the general safety of the drug for long term treatment. The
      mechanisms of action of MTX in inflammation are complex but increasingly better
      understood. Current publications show that first steps have been done towards
      prediction of therapeutic response and toxicity of MTX by analysis of gene
      polymorphism. Conjugates of MTX which use endogenous albumin as a drug carrier to
      synovitis as well as new receptor-specific folate inhibitors are currently tested
      in pre-clinic investigations. The goal to further develop the most successful
      principle of folate inhibition for the treatment of rheumatic diseases seems to
      be feasible.

PMID- 19838717
TI  - [Adult-onset Still's disease, Schnitzler syndrome, and autoinflammatory syndromes
      in adulthood].
AB  - Adult-onset Still's disease (AoSD), Schnitzler syndrome, and cases of adult-onset
      autoinflammatory syndromes [10-15% of cases of familial Mediterranean fever (FMF)
      and tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS)]
      are characterized by a genetic predisposition, with increased interleukin (IL)
      1beta and IL-18 production and TNF-alpha signaling, respectively. As a result,
      periodic fever and inflammation at barrier tissues (synovial tissues, serous
      membranes, and the skin) are encountered in such patients. Pathophysiological
      insights into these diseases have renewed interest in research on IL-1beta in
      rheumatic diseases and have opened new therapeutic avenues. Recently published
      studies have shown that patients with Schnitzler syndrome, methotrexate
      refractory AoSD, and colchicine-refractory FMF or contraindications to
      colchicines in FMF respond well to treatment with the soluble IL-1 receptor
      antagonist anakinra. For TRAPS patients, the p75 TNF-alpha receptor/Fc-IgG1
      fusion protein etanercept is the treatment of first choice.

PMID- 19838718
TI  - [Crystal-induced activation of the inflammasome: gout and pseudogout].
AB  - Crystals in tissues lead the innate immune system to the same kind of acute
      response seen with pathogens. Via activation of the inflammasome, interleukin-1
      (IL-1) is released, which upregulates mediators such as cyclooxygenase, tumor
      necrosis factor, and IL-8 and induces an acute granulocytic inflammation.
      Therefore, in addition to nonsteroidal anti-inflammatory drugs (NSAIDs),
      steroids, and colchicine, IL-1 blockers appear to be effective. Large clinical
      trials have already been initiated. Such an approach could constitute a valuable
      alternative for patients with contraindications or insufficient response to
      NSAIDs. After the attack has subsided, control of uric acid metabolism is
      central. At least several of the responsible urate transporters have been
      unraveled, which could lead to more focused therapy in the future. At present,
      diet and blockade of uric acid synthesis remain the main pillars of therapy. The
      new xanthine oxidase inhibitor febuxostat constitutes a novel option for patients
      with renal insufficiency or intolerance to allopurinol.

PMID- 19838719
TI  - Extremity soft tissue sarcomas presented as hematomas.
AB  - INTRODUCTION: Soft tissue sarcoma (STS) with extensive intra-tumoral hemorrhage
      is an infrequently described entity, usually misdiagnosed as intra-muscular
      hematoma. The outcomes in this group of patients have not been previously
      described. MATERIALS AND METHODS: We retrospectively identified 15 patients, with
      initial clinical or imaging diagnosis of hematoma, or hematoma versus hemorrhagic
      sarcoma, although final diagnosis of high-grade STS was established in all cases.
      RESULTS: The most common location was the thigh. Three patients had a bleeding
      predisposition. Ten patients were referred for further evaluation with the
      initial diagnosis of muscle strain/hematoma, hematoma versus abscess in one,
      whereas four were referred for soft tissue mass evaluation. Final diagnosis was
      made by one biopsy in only 53% of patients. Mean time to diagnosis for patients
      with two biopsies was 7 months from initial presentation. Histologic diagnosis
      was malignant fibrous histiocytoma in ten patients. Surgical treatment included
      tumor resection in eleven and amputation in three patients. One patient had lung
      metastatic disease at presentation and eight developed lung metastases within a
      median time of 7 months. CONCLUSION: We suggest that an STS masquerading as
      hematoma should be suspected when the mechanism and the energy of the trauma do
      not justify the clinically detected severity of the injury, or the lesion does
      not follow the expected clinical course of resolution after initial conservative
      management. Bleeding predisposition does not exclude malignancy. The evacuation
      of hematomas should include pathologic examination of tissue. Prognosis is dismal
      due to early metastatic disease.

PMID- 19838721
TI  - Effect of expansion technique of uterine incision on maternal blood loss in
      cesarean section.
AB  - OBJECTIVE: The purpose of this study was to determine whether the method used to
      expand the uterine incision (sharp vs. blunt) for cesarean section (CS) affects
      maternal blood loss. METHOD: A prospective study conducted on 200 nulliparous who
      underwent lower segment transverse CS divided into two groups. One hundred women
      were assigned to have blunt expansion of the uterine incision by fingers of the
      surgeon, and 100 women to have sharp expansion using bandage scissors. Finally, a
      comparison of two groups was made regarding blood loss, change in hematocrit,
      uterine tears and blood transfusion. P < 0.05 was considered significant.
      RESULTS: Maternal blood loss and postoperative hematocrit drop were significantly
      higher in sharp group (375 +/- 95 cm3 in blunt vs. 443 +/- 86 in sharp, P = 0.001
      and 2.4 +/- 2.6 in blunt vs. 4.1 +/- 2.6 in sharp, P = 0.001, respectively).
      There was no significant difference in the extension of uterine incision.
      CONCLUSIONS: Our findings support that blunt expansion of uterine incision during
      lower segment cesarean is safer and easier than sharp expansion.

PMID- 19838720
TI  - Changes in content and synthesis of collagen types and proteoglycans in
      osteoarthritis of the knee joint and comparison of quantitative analysis with
      Photoshop-based image analysis.
AB  - INTRODUCTION: The different cartilage layers vary in synthesis of proteoglycan
      and of the distinct types of collagen with the predominant collagen Type II with
      its associated collagens, e.g. types IX and XI, produced by normal chondrocytes.
      It was demonstrated that proteoglycan decreases in degenerative tissue and a
      switch from collagen type II to type I occurs. The aim of this study was to
      evaluate the correlation of real-time (RT)-PCR and Photoshop-based image analysis
      in detecting such lesions and find new aspects about their distribution.
      PATIENTS: We performed immunohistochemistry and histology with cartilage tissue
      samples from 20 patients suffering from osteoarthritis compared with 20 healthy
      biopsies. Furthermore, we quantified our results on the gene expression of
      collagen type I and II and aggrecan with the help of real-time (RT)-PCR.
      Proteoglycan content was measured colorimetrically. Using Adobe Photoshop the
      digitized images of histology and immunohistochemistry stains of collagen type I
      and II were stored on an external data storage device. The area occupied by any
      specific colour range can be specified and compared in a relative manner directly
      from the histogram using the "magic wand tool" in the select similar menu. In the
      image grow menu gray levels or luminosity (colour) of all pixels within the
      selected area, including mean, median and standard deviation, etc. are depicted.
      Statistical Analysis was performed using the t test. METHOD: With the help of
      immunohistochemistry, RT-PCR and quantitative RT- PCR we found that not only
      collagen type II, but also collagen type I is synthesized by the cells of the
      diseased cartilage tissue, shown by increasing amounts of collagen type I mRNA
      especially in the later stages of osteoarthritis. RESULTS: A decrease of collagen
      type II is visible especially in the upper fibrillated area of the advanced
      osteoarthritic samples, which leads to an overall decrease. Analysis of
      proteoglycan showed a loss of the overall content and a quite uniform staining in
      the different zones compared to the healthy cartilage with a classical zonal
      formation. Correlation analysis of the proteoglycan Photoshop measurements with
      the RT-PCR using Spearman correlation analysis revealed strong correlation for
      Safranin O and collagen type I, medium for collagen type II and glycoprotein but
      weak correlation between PCR aggrecan results. CONCLUSION: Photoshop-based image
      analysis might become a valuable supplement for well known histopathological
      grading systems of lesioned articular cartilage.

PMID- 19838722
TI  - Turkey's experience of robotic-assisted laparoscopic hysterectomy: a series of 25
      consecutive cases.
AB  - PURPOSE: To present the outcomes of the first 25 robotic-assisted hysterectomies
      from Turkey. METHOD: A total of 25 patients who underwent robotic-assisted
      hysterectomy (RAH) for benign conditions were included in the study. Patients'
      demographics, surgical procedures, operative and postoperative complications,
      hospital stay, conversion to laparotomy, time data including all operative times,
      uterus weight and estimated blood loss (EBL) were recorded. All hysterectomies
      were American Association of Gynecologic Laparoscopists type IVE. RESULTS: All
      hysterectomies were completed robotically with no conversion to laparotomy. The
      mean and range of the operating time were 104.1 and 47-176 min, respectively. The
      mean hysterectomy time was 40.5 min (range 14-77). The mean cuff incision time
      and cuff suturation time were 6.8 min (range 2-18) and 16.4 min (range 7-40),
      respectively. The mean set-up time was 30.4 min (range 17-41 min). The mean
      docking time was 4.3 min (range 2-9 min). The mean console time was 74.2 min
      (range 30-137). The mean and range of the anesthesia time were 133.8 min and 75
      210 min, respectively. The averages of EBL and uterus weight were calculated as
      38.2 cc and 221.9 g, respectively. Three complications occurred: one
      postoperative paralytic ileus and the others were peroperative vaginal cuff
      lacerations during the removal of the specimen through the vagina. CONCLUSION:
      Robotic-assisted hysterectomy (RAH) is feasible and safe for women with benign
      uterine pathologies, although it has limitations that may be overcome in the
      future.

PMID- 19838723
TI  - Significance of nipple enhancement of Paget's disease in contrast enhanced breast
      MRI.
AB  - PURPOSE: To evaluate significance of nipple enhancement of Paget's disease in
      contrast enhanced (CE) breast MRI. METHODS: Ten patients of biopsy proven Paget's
      disease were included in this study. Preoperative mammogram and ultrasonogram
      (US) were obtained in all 10 patients, and 8 patients underwent CE breast MRI
      prior to surgery. Mammographic and US findings were reviewed retrospectively. On
      MRI, morphology (flattening or asymmetry or thickening) and enhancement of
      pathologically involved nipple were analyzed comparing with the opposite side,
      and also reviewed the abnormal enhancing lesion in the breast parenchyma.
      RESULTS: Morphologic changes of the nipple were detected in 2 out of 10 patients
      by mammogram and 6 out of 10 patients by US. On MRI, morphologic change was also
      revealed in 7 patients and abnormal enhancement of involved nipple was observed
      in all 8 patients. Associated parenchymal enhancing lesions were proved to be
      DCIS (7 out of 10) and invasive ductal carcinoma (2 out of 10). Remaining one
      patient had no underlying breast parenchymal malignancy. CONCLUSION: CE breast
      MRI allows for the correct detection of nipple involvement of Paget's disease
      even when clinical information or mammographic/US findings are not provided.

PMID- 19838724
TI  - Expression of cAMP response element-binding protein in the duct system of the
      mouse submandibular gland.
AB  - The submandibular gland (SMG) of mice shows a marked sexual dimorphism in which a
      duct portion called the granular convoluted tubule (GCT) is developed
      preferentially in males during puberty. The administration of testosterone to
      female mice causes the conversion of striated duct (SD) cells into GCT cells, but
      the underlying molecular mechanisms are unclear. Cyclic AMP response element
      binding protein (CREB) is a transcription factor functioning downstream of a
      variety of signal transduction pathways. In the present study, we examined the
      expression, activation and cellular localization of CREB in the mouse SMG using
      Western blotting and immunohistochemistry. Both total CREB (t-CREB) and
      phosphorylated CREB (p-CREB) were significantly more abundant in the female than
      in the male gland and were localized to the nuclei of intercalated duct cells and
      a subpopulation of SD cells. In contrast, the GCT cells in males were negative
      for t- and p-CREB. The levels of CREB in the SMG were increased by castration in
      males and decreased by repeated administration of testosterone to females or
      castrated males. From 3 h after a single administration of testosterone to
      females, many SD cells temporarily gained nuclear immunoreactivity for both t-
      and p-CREB, which was lost as the cells were converted to GCT cells by 24 h.
      These results suggest the involvement of CREB in the androgen-dependent
      differentiation of the duct system in the mouse SMG.

PMID- 19838725
TI  - Stimulus-response bindings contribute to item switch costs in working memory.
AB  - In counter updating tasks, responses are typically faster when items repeat than
      when they change (item switch costs). The present study explored the contribution
      of stimulus-response bindings to these item switch costs. In two experiments, we
      orthogonally manipulated the repetition/switch of to-be-counted items and the
      repetition/switch of required manual responses. Item switch costs were
      considerably lower when item switches were accompanied by response switches than
      when accompanied by response repetitions. Experiment 2 showed that, although
      there was also a smaller contribution from stimulus-stimulus bindings (i.e.,
      shape-location), the major part was due to stimulus-response bindings. These
      results show that in the widely used standard version of the counter updating
      task, a considerable portion of item switch costs is caused by the unbinding of
      stimulus-response bindings rather than by processes of switching items in working
      memory.

PMID- 19838727
TI  - Pathologic characteristics of resected squamous cell carcinoma of the trachea:
      prognostic factors based on an analysis of 59 cases.
AB  - While squamous cell carcinoma (SCC) is the most common tracheal malignancy, few
      reports describe the pathologic considerations that may guide intraoperative
      decisions and prognostic assessment. We reviewed 59 tracheal SCC treated between
      1985 and 2008 by segmental resection of the trachea, including resection of the
      carina in 24% and inferior larynx in 14%. We classified these tumors by grading
      histologic differentiation and microscopic features used in SCC of other sites.
      Of 59 tumors, 24% (14 of 59) were well differentiated, 49% (29 of 59) were
      moderately differentiated, and 27% (16 of 59) were poorly differentiated.
      Unfavorable prognostic factors were tumor extension into the thyroid gland (all
      of five so-afflicted patients died of tumor progression within 3 years) and
      lymphatic invasion (mean survival 4.6 versus 7.6 years). Keratinization,
      dyskeratosis, acantholysis, necrosis, and tumor thickness did not predict
      prognosis. As surgical resection is the only curative treatment; the surgeon
      should establish clean lines of resection using, as appropriate, intraoperative
      frozen section. The pathologist can provide additional important prognostic
      information, including tumor differentiation and extent, invasion of surgical
      margins, and extension into the thyroid.

PMID- 19838726
TI  - Metastatic potential of an aneurysmal bone cyst.
AB  - Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled
      cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are
      lesions reactive to local hemodynamics has been challenged after the discovery of
      specific recurrent chromosomal abnormalities. Multiple cases of malignant
      transformation of ABC into (osteo)sarcoma have been described, as well as a
      number of cases of telangiectatic osteosarcoma which had been misdiagnosed as
      ABC. We herewith document a case of a pelvic ABC metastatic to the lung, liver,
      and kidneys. Diagnosis was confirmed by the presence of a break in the USP6 gene,
      which is pathognomonic for ABC, in a pulmonary metastasis of our patient.
      Sarcomatous transformation as an explanation for this behavior was ruled out by
      demonstrating diploid DNA content in both the pulmonary lesion and the primary
      tumor.

PMID- 19838728
TI  - Overexpression of Aurora B is associated with poor prognosis in epithelial
      ovarian cancer patients.
AB  - Recent studies have indicated that Aurora B expression is related to cell
      proliferation and prognosis in many cancers, but its association with epithelial
      ovarian carcinoma is not fully understood. Therefore, we examined the Aurora B
      kinase expression in epithelial ovarian cancer patients. Using
      immunohistochemistry, the expression levels of Aurora B and phosphohistone H3
      (Ser(10)) (mitosis-specific marker) were measured in 156 patients with epithelial
      ovarian cancer. The expression levels of Aurora B at the protein and messenger
      RNA levels were examined using Western blotting and reverse transcriptase
      polymerase chain reaction. In total, 53 tumorous ovarian samples (34.0%) showed
      Aurora B overexpression, which was significantly higher than that found in the 15
      normal ovarian tissue samples (0%, p = 0.006). The overexpression of Aurora B was
      also significantly higher in cases showing phosphohistone H3 (Ser(10))
      overexpression (44.3% vs. 27.4%, p = 0.03). In addition, the expression of Aurora
      B in poorly and moderately differentiated carcinomas of the ovary was
      significantly higher than in well-differentiated carcinomas (53.6% vs. 28.2%
      vs.10.0%, respectively, p = 0.02). The overexpression of Aurora B was
      significantly higher in cases with lymph node metastasis (p = 0.01) and a
      positive ascites cytology (p = 0.008). Overall, the Aurora B overexpression group
      demonstrated a significantly shorter progression-free survival (p = 0.001) and
      overall survival (p = 0.023) than the Aurora B low expression group using
      univariate analysis (log-rank statistic). Aurora B is an effective predictor of
      aggressive epithelial ovarian carcinoma in terms of differentiation, metastasis,
      and prognosis.

PMID- 19838729
TI  - Danger of low pressure alarm failure in preterm infants on continuous positive
      airway pressure.
AB  - In certain settings of conventional continuous positive airway pressure (CPAP)
      application, the ventilator may not be able to detect dislodgement of the prongs.
      This occurs especially in settings with high flow and small prongs. We
      investigated the relation between ventilator flows, size of the nasal prongs, and
      pressure generated within the ventilator circuit due to the flow resistance of
      the prongs. We studied a Baby-flow CPAP connected to a Babylog 8000plus
      ventilator. Five prongs of increasing size (x-small, small, medium, large, x
      large) and one nose mask were connected to the CPAP in turn. Starting at 30 lpm,
      the flow was reduced in 2 lpm steps. The dynamic pressure caused by the flow
      resistance of the prongs within the ventilator circuit was recorded. For all
      devices, we observed a correlation between the reduction of the flow and the
      reduction in pressure within the ventilator circuit. However, the flow resistance
      of the x-small prongs generated the highest dynamic pressure (30 mbar at 22 lpm)
      within the ventilator circuit while the mask gave rise to the lowest pressure (9
      mbar at 30 lpm). The pressure value generated with x-small prongs at low flow
      rate was observed at high flow rate with x-large prongs or with a mask. We
      conclude that in settings with high flow rates, low CPAP levels, and small
      prongs, the resistance of the prongs will create enough dynamic pressure within
      the ventilator circuit to permit the ventilator to compensate a large leakage
      flow by closing the expiratory valve. Thus, in case of dislodgement of the
      prongs, the pressure within the ventilator circuit will not decrease below the
      alarm level, and the machine will not be able to generate an alarm.

PMID- 19838731
TI  - Microcephaly, sensorineural deafness and Currarino triad with duplication
      deletion of distal 7q.
AB  - Currarino syndrome (CS) is a peculiar form of caudal regression syndrome [also
      known as autosomal dominant sacral agenesis (OMIM no. 176450)] characterised by
      (1) partial absence of the sacrum with intact first sacral vertebra, (2) a pre
      sacral mass and (3) anorectal anomalies (Currarino triad). We studied a 3-year
      old girl with Currarino triad who had additional systemic features and performed
      array comparative genomic hybridisation to look for chromosomal abnormalities.
      This girl had the typical spectrum of anomalies of the CS including (a) partial
      sacral agenesis (hemisacrum with remnants of only sacral S1-S2 vertebrae and a
      residual S3 vertebral body) associated with complete coccygeal agenesis, (b) pre
      intrasacral dermoid, (c) intra-dural lipoma, (d) ectopic anus and (e) tethered
      cord. She had, in addition, pre- and post-natal growth impairment (<3rd
      percentile), severe microcephaly (<-3 SD) with normal gyration pattern and lack
      of cortical thickening associated with a hypoplastic inferior vermis, facial
      dysmorphism, sensorineural deafness and decreased serum levels of IGF-1. A de
      novo 10.3-Mb duplication of 7q34-q35 and an 8.8-Mb deletion on 7q36 were
      identified in this patient. The Homeobox HLXB9 (CS) gene is contained within the
      deletion accounting for the CS phenotype including microcephaly. The spectrums of
      associated abnormalities in the IGF-1 deficiency growth retardation with
      sensorineural deafness and mental retardation syndrome (OMIM no. 608747) are
      discussed. To the best of our knowledge, this is the first reported case of a
      patient with distal 7q chromosomal imbalance and features of CS triad (including
      microcephaly) and the first documented case of a patient with normal gyration
      pattern microcephaly. The spectrum of associated anomalies in this newly
      recognised phenotype complex consists of growth failure, typical facial anomalies
      with additional (previously unreported) nervous system abnormalities (e.g.
      sensorineural deafness) and somatomedin C deficiency.

PMID- 19838732
TI  - Insecticidal activity of essential oils from native medicinal plants of Central
      Argentina against the house fly, Musca domestica (L.).
AB  - The insecticidal activity of nine essential oils (EOs) against the house fly
      (Musca domestica) was evaluated by placing flies in a screw-cap glass jar holding
      a piece of EO-treated cotton yarn. The dose necessary to kill 50% of flies
      (LC(50)) in 30 min was determined at 26 +/- 1 degrees C. The EOs showed LC(50)
      values ranging from 0.5 to 46.9 mg/dm(3). The EO from Minthostachys verticillata
      was the most potent insecticide (LC(50) = 0.5 mg/dm(3)) followed by EOs from
      Hedeoma multiflora (LC(50) = 1.3 mg/dm(3)) and Artemisia annua (LC(50) = 6.5
      mg/dm(3)). The compositions of the nine EOs, obtained by hydrodistillation of
      medicinal herbs, were analyzed by gas chromatography/mass spectroscopy. These
      analyses showed that (4R)(+)-pulegone (69.70%), menthone (12.17%), and limonene
      (2.75%) were the principal components of M. verticillata EO. (4R)(+)-pulegone was
      also the main constituent (52.80%) of H. multiflora, while artemisia ketone
      (22.36%) and 1,8-cineole (16.67%) were the major constituents of A. annua EO. The
      terpene (4R)(+)-pulegone showed a lower toxicity (LC(50) = 1.7 mg/dm(3)) than M.
      verticillata or H. multiflora EOs. Dimethyl 2,2-dichlorovinyl phosphate, selected
      as a positive control, showed an LC(50) of 0.5 mg/dm(3). EOs from M. verticillata
      and H. multiflora show promise as natural insecticides against houseflies.

PMID- 19838733
TI  - Life cycle of Sarcocystis camelicanis infecting the camel (Camelus dromedarius)
      and the dog (Canis familiaris), light and electron microscopic study.
AB  - In the present study, the heteroxeneous life cycle of Sarcocystis sp. infecting
      camels were studied. A total of 180 slaughtered camels collected from different
      localities in Egypt were investigated for sarcocysts. Only 116 animals were found
      to be infected (the infection rate was 64%). Muscle samples of esophagus,
      diaphragm, tongue, skeletal, and heart muscles were examined. Exclusively,
      microscopic sarcocysts were detected in all examined organs. The infection rates
      of the esophagus, diaphragm, tongue, skeletal, and heart muscles were 60%, 50%,
      40%, 40%, and 10%, respectively. By means of transmission electron microscopy,
      details of the ultrastructure of the sarcocysts were studied. The specific
      architecture and ornaments of the cyst wall, its protrusions, and the cyst
      interior were recorded. Unique features of protrusions of the primary cyst wall,
      the knob-like structures, arise around each protrusion. Experimental infection of
      carnivores by feeding heavily infected camel muscles revealed that the dog, Canis
      familiaris, is the only final host of the present Sarcocystis species. Gamogony,
      sporogonic stages, and characteristics of sporulated oocysts were also
      investigated.

PMID- 19838734
TI  - Amaranthus oleracea and Euphorbia hirta: natural potential larvicidal agents
      against the urban Indian malaria vector, Anopheles stephensi Liston (Diptera:
      Culicidae).
AB  - Malaria control in developing countries is based largely on vector eradication by
      the use of mosquito larvicides which is an ideal method for controlling mosquito
      and the related epidemics. On account of ecohazardous nature, nontarget
      specificity of chemical insecticides and evidences of developing resistance
      against them in the exposed species, currently, importance of secondary plant
      metabolites has been acknowledged. Insecticides of plant origin are
      environmentally safe, degradable, and target specific. In view of this fact, the
      present work highlights the larvicidal property of extracts of Amaranthus
      oleracea and Euphorbia hirta against the third instar larvae of Anopheles
      stephensi, the urban malaria vector. LC(50) values for the carbon tetrachloride
      fraction of A. oleracea against larvae are 17,768.00 and 13,780.00 ppm after 24
      and 48 h of exposure accordingly. For the methanol extract of the same, LC(50)
      values are 15,541.00 and 10,174.00 ppm after 24 and 48 h of exposure. In the case
      of petroleum ether extract, LC(50) values after 24 and 48 h of exposure are
      848.75 and 311.50 ppm. LC(50) values for carbon tetrachloride extracts of E.
      hirta against the larvae are 11,063.00 and 10,922.00 ppm after 24 and 48 h of
      exposure, respectively. For methanol extract of the same extract, the LC(50)
      values are 19,280.00 and 18,476.00 ppm after 24 and 48 h of exposure. In the case
      of petroleum ether extract, LC(50) values after a 24- and 48-h exposure period
      are 9,693.90 and 7,752.80 ppm. The results obtained for petroleum extracts of A.
      oleracea are encouraging and there are probabilities that the active principle
      contained in this extract may be more effective than its crude form and may serve
      as ecofriendly mosquito larvicide.

PMID- 19838735
TI  - Gyrodactylus species (Monogenea: Gyrodactylidae) on the cichlid fishes of
      Senegal, with the description of Gyrodactylus ergensi n. sp. from Mango tilapia,
      Sarotherodon galilaeus L. (Teleostei: Cichilidae).
AB  - The first record of Gyrodactylus species Nordmann, 1832 on the cichlid fish from
      Senegal is reported. Gyrodactylus parasites were found on four host species
      studied, Hemichromis fasciatus, Hemichromis letournaeuxi, Oreochromis niloticus,
      and Sarotherodon galilaeus. Gyrodactylus cichlidarum Paperna (Bamidgeh 13:14-29,
      1968) were collected from H. fasciatus, and its identity was confirmed based on
      the morphometrical comparison with the holotype specimens of G. cichlidarum. Only
      one specimen of Gyrodactylus sp. was noted on H. letournaeuxi. The gyrodactylid
      specimens on O. niloticus and S. galilaeus were described as Gyrodactylus ergensi
      n. sp. based on the detailed morphometrical analysis supported by sequencing. The
      haptoral sclerites of G. ergensi n. sp., which closely resemble those of
      Gyrodactylus nyanzae Paperna, 1973, are compared with the type material and
      discussed. A partial sequence of the internal transcribed spacer recombinant DNA
      (ITS rDNA) was obtained from two specimens of G. ergensi, and a close
      relationship between G. ergensi n. sp. and G. cichlidarum is suggested based on
      92% similarity in ITS rDNA region.

PMID- 19838736
TI  - Genome-wide identification of NBS-encoding resistance genes in Brassica rapa.
AB  - Nucleotide-binding site (NBS)-encoding resistance genes are key plant disease
      resistance genes and are abundant in plant genomes, comprising up to 2% of all
      genes. The availability of genome sequences from several plant models enables the
      identification and cloning of NBS-encoding genes from closely related species
      based on a comparative genomics approach. In this study, we used the genome
      sequence of Brassica rapa to identify NBS-encoding genes in the Brassica genome.
      We identified 92 non-redundant NBS-encoding genes [30 CC-NBS-LRR (CNL) and 62 TIR
      NBS-LRR (TNL) genes] in approximately 100 Mbp of B. rapa euchromatic genome
      sequence. Despite the fact that B. rapa has a significantly larger genome than
      Arabidopsis thaliana due to a recent whole genome triplication event after
      speciation, B. rapa contains relatively small number of NBS-encoding genes
      compared to A. thaliana, presumably because of deletion of redundant genes
      related to genome diploidization. Phylogenetic and evolutionary analyses suggest
      that relatively higher relaxation of selective constraints on the TNL group after
      the old duplication event resulted in greater accumulation of TNLs than CNLs in
      both Arabidopsis and Brassica genomes. Recent tandem duplication and ectopic
      deletion are likely to have played a role in the generation of novel Brassica
      lineage-specific resistance genes.

PMID- 19838737
TI  - Separation characteristics of animal cells using a dielectrophoretic filter.
AB  - The separation characteristics of a wire-wire type dielectrophoretic (DEP) filter
      were evaluated using animal cells. The separation of cells with different
      activities was examined using a DEP filter. The specific growth rate of the cells
      in retention liquid was larger than that in permeation liquid. From the culture
      results of the separated cells, it becomes clear that the specific growth rate of
      the cells of the retention liquid was higher than that of the cells of the
      permeation liquid. Furthermore, as a result of separating cells two kinds of cell
      suspensions using the DEP filter, the difference between the retention ratios of
      the two groups of obtained cells was about 20% at maximum.

PMID- 19838738
TI  - Middle-term use of Cinacalcet in paediatric dialysis patients.
AB  - The effects of the calcimimetic drug Cinacalcet were assessed in six children
      with uncontrolled hyperparathyroidism secondary to stage 5 chronic kidney disease
      (CKD). Data were collected retrospectively regarding bone biochemistry and
      medications. Patients were between the ages of 11 months and 14 years on
      commencing Cinacalcet at initial doses of 0.4-1.4 mg/kg. Treatment, which was
      well tolerated in the majority and still on going in five patients, was for
      periods ranging between 3 months and 3 years. All six cases saw at least an 86%
      reduction in serum parathyroid hormone (PTH). Hypophosphataemia and/or
      hypocalcaemia were observed in three cases. Overall, achievement of UK Renal
      Association targets for corrected calcium (Ca), phosphate (P) and the calcium x
      phosphate product (Ca x P) were unaffected. We conclude that Cinacalcet is an
      effective treatment for correcting and sustaining correction of uncontrollable
      PTH levels seen in a difficult group of patients. Importantly, it has allowed the
      avoidance of parathyroidectomy for a significant time period in all cases. There
      remain questions about the effect of Cinacalcet on linear growth amongst
      paediatric dialysis patients, and future studies should aim to address this.

PMID- 19838739
TI  - [An abbreviated version of RDC/TMD].
AB  - BACKGROUND: The aim of this study was to develop a short diagnostic test for pain
      related craniomandibular disorders (CMD) based on the Research Diagnostic
      Criteria for Temporomandibular Disorders (RDC/TMD). MATERIAL AND METHOD:
      Participants included 1,177 CMD patients and 896 general population subjects who
      were examined according to the RDC/TMD. This new diagnostic short test consisted
      of a combination of the least amount of RDC/TMD items that distinguished between
      patients and subjects with a sensitivity of > or =70% and a specificity of > or
      =90%. The diagnostic test items were selected from all available RDC/TMD items
      using best subset logistic regression. RESULTS: The question about the presence
      of facial pain achieved a sensitivity of 96% and a specificity of 95%. The lower
      limits of the confidence interval for test accuracy measures exceeded the
      postulated thresholds specified for test development. Assuming a CMD pain
      prevalence of 10% in the general population this short test resulted in a
      positive predictive value of 80% and a negative predictive value of >99%.
      CONCLUSION: A single question about facial pain is a strong predictor for a pain
      related CMD disorder and could provide an effective CMD short test.

PMID- 19838740
TI  - [Spinal cord stimulation at the level of the conus medullaris : treatment option
      for therapy-resistant postoperative neuralgia of the pudendal nerve].
AB  - Injuries of the pudendal nerve, due to a perineal tear during delivery for
      example, can cause significant and debilitating neurological deficits. Aconuresis
      and anal incontinence, as well as sensory loss of the outer genitals or even
      impotency in men are the well known consequences. In addition some patients
      suffer from a severe neuropathic pain syndrome which is resistant to conservative
      treatment options. Epidural spinal cord stimulation at the level of the terminal
      cone of the spinal cord may be a new and successful therapeutic concept in
      otherwise untreatable cases.

PMID- 19838741
TI  - [Chronic pain alters the structure of the brain].
AB  - Local morphologic alterations of the brain in areas ascribable to the
      transmission of pain were recently detected in patients suffering from phantom
      pain, chronic back pain, irritable bowl syndrome, fibromyalgia and frequent
      headaches. These alterations were different for each pain syndrome, but
      overlapped in the cingulate cortex, the orbit frontal cortex, the insula and
      dorsal pons. As it seems that chronic pain patients have a common "brain
      signature" in areas known to be involved in pain regulation, the question arises
      whether these changes are the cause or the consequence of chronic pain. The in
      vivo demonstration of a loss of brain gray matter in patients suffering from
      chronic pain compared to age and sex-matched healthy controls could represent the
      heavily discussed neuroanatomical substrate for pain memory.

PMID- 19838742
TI  - Do patient attributes predict oncologist empathic responses and patient
      perceptions of empathy?
AB  - PURPOSE: Most patients with advanced cancer experience negative emotion. When
      patients express emotions, oncologists rarely respond empathically. Oncologists
      may respond more empathically to some patients, and patients may perceive
      different levels of empathy and trust given past documentation of disparities in
      cancer care. METHODS: We audio-recorded 264 outpatient encounters between
      oncologists and patients with advanced cancer at three sites. We examined whether
      patient gender, age, race, marital status, education, economic security, and
      length of relationship with oncologist were related to oncologist empathic
      responses to patient's negative emotion and patient's perceptions of oncologist
      empathy and trust. RESULTS: Half (51%) of the patients expressed a negative
      emotion. Oncologists sometimes responded with empathy (29%). Oncologists were
      equally empathic with all patients, except they were more empathic with patients
      with low economic security compared with those reporting high economic security
      (p = .002). Patients with low economic security viewed oncologists as more
      empathic (p = .06) compared with those with moderate security. Married patients
      also viewed oncologists as more empathic (p = .04). Patients who knew their
      oncologist for more than a year had more trust than patients who knew their
      oncologists for less time (p = .02). CONCLUSIONS: Oncologists, in general, did
      not respond empathically to patient's negative emotion, and did this equally for
      most patients. Oncologists responded more empathically to patients who were less
      economically advantaged. In turn, patients with lower economic security perceived
      more empathy. Although oncologists need more education in responding
      empathically, they may not need to correct many biases in care.

PMID- 19838743
TI  - Optimization of culture conditions of Arnica montana L.: effects of mycorrhizal
      fungi and competing plants.
AB  - Arnica montana is a rare plant that needs special protection because of its
      intensive harvesting for medicinal purposes. The present work was aimed at
      finding optimal culture conditions for Arnica plants in order to enable their
      successful reintroduction into their natural stands. Plants were cultivated under
      controlled greenhouse conditions on substrata with different nitrogen (N)
      concentration. As Arnica is always colonized by arbuscular mycorrhizal fungi
      (AMF) in nature, a fact that has been overlooked in other similar projects, we,
      here, applied and tested different inocula. We found that they differed in their
      effectiveness, both in establishing symbiosis, assessed by the colonization
      parameters, and in improving the performance of Arnica, evaluated by the
      photosynthetic parameters derived from the fluorescence transients (JIP-test),
      with the inocula containing G. intraradices or composed of several Glomus strains
      being the most effective. The comparison was possible only on substrata with
      medium N, since high N did not permit the formation of mycorrhiza, while at low
      N, few nonmycorrhizal plants survived until the measurements and mycorrhizal
      plants, which were well growing, exhibited a high heterogeneity. Analysis of
      secondary metabolites showed clearly that mycorrhization was associated with
      increased concentrations of phenolic acids in roots. For some of the inocula
      used, a tendency for increase of the level of phenolic acids in shoots and of
      sesquiterpene lactones, both in roots and in shoots, was also observed. We also
      studied the interactions between A. montana and Dactylis glomerata, known to
      compete with Arnica under field conditions. When specimens from both species were
      cultured together, there was no effect on D. glomerata, but Arnica could retain a
      photosynthetic performance that permitted survivability only in the presence of
      AMF; without AMF, the photosynthetic performance was lower, and the plants were
      eventually totally outcompeted.

PMID- 19838744
TI  - Expert's comment concerning Grand Rounds case entitled "Spontaneous and
      idiopathic chronic spinal epidural hematoma: two case reports and review of the
      literature" (by S. Sarubbo, F. Garofano, G. Maida, E. Fainardi, E. Granieri, M.
      A. Cavallo).

PMID- 19838745
TI  - Intracranial infectious aneurysms: a comprehensive review.
AB  - Intracranial infectious aneurysms, or mycotic aneurysms, are rare infectious
      cerebrovascular lesions which arise through microbial infection of the cerebral
      arterial wall. Due to the rarity of these lesions, the variability in their
      clinical presentations, and the lack of population-based epidemiological data,
      there is no widely accepted management methodology. We undertook a comprehensive
      literature search using the OVID gateway of the MEDLINE database (1950-2009)
      using the following keywords (singly and in combination): "infectious,"
      "mycotic," "cerebral aneurysm," and "intracranial aneurysm." We identified 27
      published clinical series describing a total of 287 patients in the English
      literature that presented demographic and clinical data regarding presentation,
      treatment, and outcome of patients with mycotic aneurysms. We then synthesized
      the available data into a combined cohort to more closely estimate the true
      demographic and clinical characteristics of this disease. We follow by presenting
      a comprehensive review of mycotic aneurysms, highlighting current treatment
      paradigms. The literature supports the administration of antibiotics in
      conjunction with surgical or endovascular intervention depending on the character
      and location of the aneurysm, as well as the clinical status of the patient.
      Mycotic aneurysms comprise an important subtype of potentially life-threatening
      cerebrovascular lesions, and further prospective studies are warranted to define
      outcome following both conservative and surgical or endovascular treatment.

PMID- 19838746
TI  - Response to Dr. Belthur's letter to the editor on the article: "Talonavicular
      joint arthrodesis for the treatment of pes planus valgus in older children and
      adolescents with cerebral palsy".

PMID- 19838747
TI  - [Pediatric radiological diagnostics in suspected child abuse].
AB  - Advanced and specialized radiological diagnostics are essential in the case of
      clinical suspicion of pediatric injuries to the head, thorax, abdomen, and
      extremities when there is no case history or when "battered child syndrome" is
      assumed on the basis of inadequate trauma. In particular, the aim of this
      sophisticated diagnostic procedure is the detection of lesions of the central
      nervous system (CNS) in order to initiate prompt medical treatment. If diagnostic
      imaging shows typical findings of child abuse, accurate documented evidence of
      the diagnostic results is required to prevent further endangerment of the child's
      welfare.

PMID- 19838750
TI  - Distinct evolutionary patterns between two duplicated color vision genes within
      cyprinid fishes.
AB  - We investigated the molecular evolution of duplicated color vision genes (LWS-1
      and SWS2) within cyprinid fish, focusing on the most cavefish-rich genus-
      Sinocyclocheilus. Maximum likelihood-based codon substitution approaches were
      used to analyze the evolution of vision genes. We found that the duplicated color
      vision genes had unequal evolutionary rates, which may lead to a related function
      divergence. Divergence of LWS-1 was strongly influenced by positive selection
      causing an accelerated rate of substitution in the proportion of pocket-forming
      residues. The SWS2 pigment experienced divergent selection between lineages, and
      no positively selected site was found. A duplicate copy of LWS-1 of some
      cyprinine species had become a pseudogene, but all SWS2 sequences remained intact
      in the regions examined in the cyprinid fishes examined in this study. The
      pseudogenization events did not occur randomly in the two copies of LWS-1 within
      Sinocyclocheilus species. Some cave species of Sinocyclocheilus with numerous
      morphological specializations that seem to be highly adapted for caves, retain
      both intact copies of color vision genes in their genome. We found some novel
      amino acid substitutions at key sites, which might represent interesting target
      sites for future mutagenesis experiments. Our data add to the increasing evidence
      that duplicate genes experience lower selective constraints and in some cases
      positive selection following gene duplication. Some of these observations are
      unexpected and may provide insights into the effect of caves on the evolution of
      color vision genes in fishes.

PMID- 19838751
TI  - Reexcision of soft tissue sarcoma: sufficient local control but increased rate of
      metastasis.
AB  - BACKGROUND: Assuming a benign tumor, soft tissue sarcomas are often treated by
      inadequate resection. The concept of reexcision in these patients is still under
      debate. Therefore, it was our goal to evaluate the results of this treatment with
      particular respect to residual tumor. METHODS: During a 14-year period, a total
      of 143 patients were referred to Heinrich-Heine-University Dusseldorf and the
      University of Hamburg [corrected] after unplanned excision. Reexcision was
      performed in 139 patients. The assessed endpoints were local recurrence-free
      survival, distant metastasis-free survival, and tumor-related mortality.
      Univariate and multivariate analyses were performed using a log-rank test and
      Cox's proportional-hazard models. RESULTS: Over a median observation period of
      109 months, local recurrence appeared in 18 patients (12%) and distant metastasis
      in 46 patients (33%). Residual tumor was detected in 43 patients (31%) and was
      significantly associated with reduced relapse-free and overall survival. Local
      recurrence, however, was not affected. CONCLUSIONS: Despite an incomplete initial
      resection, reexcision enables local control similar to that in patients without
      residual tumor. Still, these patients have a worse prognosis owing to an
      increased rate of distant metastasis; therefore, patients with soft tissue masses
      of unknown identity should be transferred to centers that specialize in treating
      sarcomas for adequate initial resection.

PMID- 19838752
TI  - Eight-year experience with minimally invasive cardiothoracic surgery.
AB  - BACKGROUND: Over the past decade, minimally invasive cardiac surgery (MICS) has
      emerged as an accepted approach for the management of cardiac disease that
      requires a surgical solution. We report the results of an 8-year, single
      institution experience with MICS. METHODS: Between January 1, 2000 and December
      31, 2007, a total of 910 patients underwent MICS. Major cases included aortic
      valve procedures (71, 7.8%), coronary artery bypass grafting (96, 10.5%),
      atrioseptal defect repair (103, 11.3%), and mitral valve procedures (507, 55.7%).
      Major outcomes of interest included the complication and mortality rates.
      RESULTS: The mean age of the patients was 57 +/- 15 years; the mean ejection
      fraction was 55% +/- 11%; and the mean body mass index was 26.1 +/- 4.9. Overall,
      782 cases (85.9%) were performed through a mini-thoracotomy. Most of the cases
      were accomplished through central cannulation (765, 84.0%), and venous drainage
      was most commonly performed in a bicaval fashion (percutaneous superior vena cava
      and percutaneous inferior vena cava). The mean aortic cross-clamp and
      cardiopulmonary bypass (CPB) times were 58.1 +/- 44.9 and 101.9 +/- 66.8 min,
      respectively. Conversion to full sternotomy occurred in 10 patients, and the
      median length of stay in hospital was 6 days. The overall complication rate was
      8.8%, and the 30-day mortality rate was 2.9%. In the multivariate logistic
      regression analysis, risk factors associated with in-hospital complications
      included age, CPB time, arterial cannulation location, conversion from off-CPB to
      on-CPB, hepatic insufficiency, and diabetes. In the multivariate hazards
      regression analysis, risk factors associated with mortality included
      postoperative stroke, renal failure, and sternal wound infection; CPB time; and
      previous surgery. CONCLUSIONS: In our experience, minimally invasive approaches
      are effective and reproducible for a variety of cardiac operations, with
      acceptable operating time durations, morbidity, and mortality.

PMID- 19838753
TI  - Surgical outcomes auditing systems in humanitarian organizations.
AB  - BACKGROUND: Operation Smile is a humanitarian volunteer-based organization that
      provides cleft care around the world. Successful primary surgery is the key to
      improving the quality of life of patients with oral clefts. A cleft surgery
      outcomes database and evaluation system has been developed and implemented.
      METHODS: During Operation Smile's "World Journey of Smiles" in November 2007, a
      total of 4100 patients were operated on during a 10-day period at 40 simultaneous
      missions in 25 countries. Photographs taken before surgery, right after surgery,
      and at the follow-up consultations were entered in a database and used as media
      to evaluate surgical outcomes objectively by independent unbiased evaluators.
      Data about complications collected during the postoperative consultations were
      also entered. RESULTS: A postoperative consultation, 6 months to 1 year after
      surgery was conducted at 24 sites, 19 of which sent back postoperative images;
      and most returned postoperative examination forms. At those 19 sites, 703 of 1917
      patients returned for a 6- to 9-month postoperative visit, for a 36.67% return
      rate. After matching before and after pictures, 562 patients were able to be
      entered into the database, allowing 580 procedures to be evaluated. Feedback
      reports have been sent to 134 volunteer surgeons around the world. Results were
      compared among sites and locations; and the places where future actions were
      needed to improve the quality of surgery were identified. CONCLUSIONS: The
      current outcomes evaluation system has proven beneficial in tracking patient
      outcomes, auditing surgical performance, and providing feedback to surgeons and
      other team members. Challenges are discussed.

PMID- 19838754
TI  - Impact of preoperative bevacizumab on complications after resection of colorectal
      liver metastases: case-matched control study.
AB  - BACKGROUND: Chemotherapy may increase postoperative morbidity and mortality after
      liver surgery. Especially bevacizumab, a monoclonal antibody against vascular
      endothelial growth factor (VEGF), could have a detrimental effect. To assess the
      impact of neoadjuvant bevacizumab on clinical outcome after hepatectomy for
      colorectal liver metastases (CRLMs) this case-matched control study was
      initiated. METHODS: The multicentric data collection was performed in the Swiss
      HPB Center of the University Hospital Zurich (CH), the Department of Digestive
      Surgery and Transplantation Strasbourg (F), and the Division of Hepato-biliary
      pancreatic surgery of "Josep Tureta" Hospital Girona (E). Consecutive patients
      operated onbetween July 2005 and December 2007 due to CRLMs who received
      neoadjuvant chemotherapy were assessed. Patients were divided in two groups:
      group A had neoadjuvant chemotherapy with bevacicumab, and group B had it without
      bevacizumab. RESULTS: No differences in overall morbidity (56 vs. 40% in the
      bevacizumab and control groups, respectively, p = 0.23) or mortality could be
      documented. Similarly, the incidence of severe postoperative complications was
      not statistically different between the bevacizumab and control groups (31 and
      18%, respectively, p = 0.31). Wound complications were comparable (11% in the
      bevacizumab group compared and 9% in the control group, p = 1.00). However,
      bevacizumab was associated with a significantly decreased incidence of
      postoperative hepatic insufficiency (7 vs. 20%, p = 0.03). CONCLUSIONS: No impact
      on the incidence or severity of complications by bevacizumab could be shown.
      Bevacizumab may even reduce the incidence of liver failure after liver surgery.

PMID- 19838755
TI  - Papyriferic acid, an antifeedant triterpene from birch trees, inhibits succinate
      dehydrogenase from liver mitochondria.
AB  - Papyriferic acid (PA) is a triterpene that is secreted by glands on twigs of the
      juvenile ontogenetic phase of resin producing tree birches (e.g., Betula
      neoalaskana, B. pendula) and that deters browsing by mammals such as the snowshoe
      hare (Lepus americanus). We investigated the pharmacology of PA as a first step
      in understanding its antifeedant effect. After oral administration to rats, PA
      and several metabolites were found in feces but not urine, indicating that little
      was absorbed systemically. Metabolism involved various combinations of hydrolysis
      of its acetyl and malonyl ester groups, and hydroxylation of the terpene moiety.
      The presence of a malonyl group suggested a possible interaction with succinate
      dehydrogenase (SDH), a mitochondrial enzyme known to be competitively inhibited
      by malonic acid. The effect of PA on the oxidation of succinate by SDH was
      examined in mitochondrial preparations from livers of ox, rabbit, and rat. In all
      three species, PA was a potent inhibitor of SDH. Kinetic analysis indicated that,
      unlike malonate, PA acted by an uncompetitive mechanism, meaning that it binds to
      the enzyme-substrate complex. The hydrolysis product of PA, betulafolienetriol
      oxide, was inactive on SDH. Overall, the evidence suggests that PA acts as the
      intact molecule and interacts at a site other than the succinate binding site,
      possibly binding to the ubiquinone sites on complex II. Papyriferic acid was
      potent (K(iEIS) ranged from 25 to 45 microM in the three species) and selective,
      as malate dehydrogenase was unaffected. Although rigorous proof will require
      further experiments, we have a plausible mechanism for the antifeedant effect of
      PA: inhibition of SDH in gastrointestinal cells decreases mitochondrial energy
      production resulting in a noxious stimulus, 5-HT release, and sensations of
      nausea and discomfort. There is evidence that the co-evolution of birches and
      hares over a large and geographically-diverse area in Northern Europe and America
      has produced marked differences in the formation of PA by birches, and the
      tolerance of hares to dietary PA. The present findings on the metabolic fate and
      biochemical effects of PA provide a rational basis for investigating the
      mechanisms underlying differences among populations of hares in their tolerance
      of a PA-rich diet.

PMID- 19838756
TI  - Vascular anomalies encountered during pancreatoduodenectomy: do they influence
      outcomes?
AB  - BACKGROUND: Because of the potential risk of hemorrhage or ischemia, the presence
      of vascular anomalies adds to the surgical challenge in pancreatoduodenectomy
      (PD). OBJECTIVE: To analyze the literature concerning the influence of aberrant
      peripancreatic arterial anatomy on outcomes of PD. MATERIALS AND METHODS: A
      systematic search using Medline and Embase for the years 1950-2008. RESULTS: The
      most common aberration in hepatic arterial anatomy is the replaced right hepatic
      artery. Other vascular abnormalities such as replaced common hepatic artery with
      a hepatomesenteric trunk and celiomesenteric trunk and arcuate ligament syndrome
      leading to celiac artery stenosis are also associated with post-PD complications.
      Damage to the biliary branches of the hepatic arteries increases the risk of
      postoperative biliary anastomotic leak. CONCLUSION: The most common abnormalities
      of the hepatic vasculature include a replaced RHA, replaced LHA, and accessory
      RHA or LHA. Celiac artery stenosis secondary to median arcuate ligament
      compression may also be encountered. Every attempt should be made to preserve the
      aberrant vessel unless their resection is oncologically indicated. Routine
      preoperative computerized tomography angiography helps to identify the hepatic
      vascular anatomy and thereby prepares the surgeon to better deal with the
      vascular anomalies intraoperatively. Increased awareness of the vascular anatomy
      would decrease the chances of intraoperative vascular injury and consequent
      postoperative complications such as biliary anastomotic leaks as well as the
      chances of postoperative hemorrhage.

PMID- 19838757
TI  - Characterizing the HER2/neu status and metastatic potential of breast cancer
      stem/progenitor cells.
AB  - INTRODUCTION: Treatment resistance, long latency, and high recurrence rates
      suggest that breast cancers arise from defective breast stem cells. HYPOTHESIS:
      Within cancers, subpopulations of cells will demonstrate differences in
      stem/progenitor potential, HER2/neu amplification, and gene expression. Related
      cells will be found in normal breast tissue. METHODS: ER-/PR-/HER2/neu + breast
      cancer cells were flow-sorted into subpopulations: (A) CD49f(+) CD24(-), (B)
      CD49f(+)CD24(+), (C) CD49f CD24(-), and (D) CD49f(-)CD24(+). Gel matrix cell
      invasion, fluorescence in situ hybridization (FISH) HER2/neu amplification, and
      qRT-PCR gene expression were measured in all groups. Cells from sorted groups
      were implanted into rat brains. Resultant tumors were analyzed by
      immunohistochemistry (IHC) and FISH. Normal breast tissue was examined by IHC.
      RESULTS: Tumor development varied among sorted groups (25-75%), but was highest
      in group A. Tumor cells were mostly CD49f(-)CD24(-), with variable fractions of
      other stem/progenitor cells. Tumors showed HER2/neu amplification, but fewer
      chromosome 17 per cell than inoculates. Group A tumors exhibited cells with
      normal chromosome 17 copy number and near normal HER2/neu amplification. Cell
      invasion was 61% higher in unsorted cells and 34-42% in sorted groups compared
      with controls. Sorted groups showed significantly different expression of
      development, proliferation, and invasion associated genes. In normal breast
      tissue, CD49f(+) cells were identified in CD14(+) CK19(-) basal epithelial layers
      of mammary glands; these were 95% CD24(+) and 60% CD44(+). CONCLUSIONS: Breast
      cancer stem/progenitor cell populations differ in tumor-initiating potential but
      are not solely responsible for metastasis. Cancer stem/progenitor cells are less
      polyploid than cancer cells in general and may not be HER2/neu amplified. In
      normal breast tissue, breast stem/progenitor cell-like populations are present.

PMID- 19838758
TI  - Do people who intend to get a flu shot actually get one?
AB  - BACKGROUND: Vaccination against seasonal influenza is far from universal among
      groups specifically recommended for vaccine. There is little research to guide
      communication with patients about vaccination. OBJECTIVE: To assess the utility
      of the self-reported intention to be vaccinated against seasonal influenza in
      predicting vaccine uptake, reasons for being unvaccinated, and willingness to be
      vaccinated based on a doctor's recommendation. METHODS: We analyzed data from a
      subset of respondents (n = 1,527) specifically recommended by the ACIP for
      vaccination against seasonal influenza who participated in two national surveys
      of adults age 18 and older conducted in November 2008 and March 2009. RESULTS:
      Over half who intended to be vaccinated had been vaccinated. Compared to those
      without intentions, those with intentions were one-fifth as likely (p < 0.01) to
      cite lack of need and five times more likely (p < 0.01) to cite "not getting
      around to being vaccinated" as main reasons for not being vaccinated. Roughly two
      fifths of those without the intention to be vaccinated indicated a willingness to
      be vaccinated based on a doctor's recommendation. CONCLUSIONS: Asking simple
      questions about the intention to be vaccinated against seasonal influenza may be
      an efficient means of identifying patients with whom extended discussion of
      vaccine benefits is warranted.

PMID- 19838759
TI  - Improvement in peripheral glucose uptake after gastric bypass surgery is observed
      only after substantial weight loss has occurred and correlates with the magnitude
      of weight lost.
AB  - INTRODUCTION: Altered gut and pancreatic hormone secretion may bolster resolution
      of insulin resistance after Roux-en-Y gastric bypass (RYGB), but the independent
      effects of weight loss and hormonal secretion on peripheral glucose disposal are
      unknown. METHODS: Two groups of nondiabetic morbidly obese patients were studied:
      RYGB followed by standardized caloric restriction (RYGB, n = 12) or caloric
      restriction alone (diet, n = 10). Metabolic evaluations (euglycemic
      hyperinsulinemic clamp, meal tolerance test) were done at baseline and 14 days
      (both groups) and 6 months after RYGB. RESULTS: At baseline, body composition,
      fasting insulin, and glucose and peripheral glucose disposal did not differ
      between groups. At 14 days, excess weight loss (EWL) was similar (RYGB, 12.7% vs.
      diet, 10.9%; p = 0.12), fasting insulin and glucose decreased to a similar
      extent, and RYGB subjects had altered postmeal patterns of gut and pancreatic
      hormone secretion. However, peripheral glucose uptake (M value) was unchanged in
      both groups. Six months after RYGB, EWL was 49.7%. The changes in fasting glucose
      and insulin levels and gut hormone secretion persisted. M values improved
      significantly, and changes in M values correlated with the % EWL (r = 0.68, p =
      0.02). CONCLUSIONS: Improvement in peripheral glucose uptake following RYGB was
      observed only after substantial weight loss had occurred and correlated with the
      magnitude of weight lost.

PMID- 19838760
TI  - Perinatal copper deficiency alters rat cerebellar purkinje cell size and
      distribution.
AB  - Copper is required for activity of several key enzymes and for optimal mammalian
      development, especially within the central nervous system. Copper-deficient (CuD)
      animals are visibly ataxic, and previous studies in rats have demonstrated
      impaired motor function through behavioral experiments consistent with altered
      cerebellar development. Perinatal copper deficiency was produced in Holtzman rat
      dams by restricting dietary copper during the last two thirds of gestation and
      lactation. Male offspring were evaluated at postnatal day 25. Compared to
      cerebella from copper-adequate pups, the CuD pups had larger Purkinje cell (PC)
      size and irregularities in the Purkinje cell monolayer. These results suggest
      that the ataxic behavioral phenotype of CuD rats may result from disrupted
      inhibitory pathways in the cerebellum. A similar PC phenotype is seen in Menkes
      disease and in mottled mouse mutants with genetic copper deficiency, suggesting
      that copper deficiency and not just specific loss of ATP7A function is
      responsible.

PMID- 19838761
TI  - Endothelin-B receptors and ventricular arrhythmogenesis in the rat model of acute
      myocardial infarction.
AB  - The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors,
      but the role of ETB-receptors is unclear. We examined the pathophysiologic role
      of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial
      infarction (MI). MI was induced by coronary ligation in two animal groups, namely
      in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a
      telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour)
      and phase II (2-24 h) post-MI, with and without prior beta-blockade. Action
      potential duration at 90% repolarization (APD90) was measured from monophasic
      epicardial recordings and indices of sympathetic activation were assessed using
      fast-Fourier analysis of heart rate variability. Serum epinephrine and
      norepinephrine were measured with radioimmunoassay. MI size was similar in the
      two groups. There was a marked temporal variation in VT/VF duration; during phase
      I, it was higher (p = 0.0087) in ETB-deficient (1,519 +/- 421 s) than in wild
      type (190 +/- 34 s) rats, but tended (p = 0.086) to be lower in ETB-deficient
      (4.2 +/- 2.0 s) than in wild-type (27.7 +/- 8.0 s) rats during phase II. Overall,
      the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher (p =
      0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate
      and in the ratio of low- to high-frequency spectra, being higher (<0.001) during
      phase I, but lower (p < 0.05) during phase II in ETB-deficient rats. Likewise, 1
      h post-MI, serum epinephrine (p = 0.025) and norepinephrine (p < 0.0001) were
      higher in ETB-deficient (4.20 +/- 0.54, 14.24 +/- 1.39 ng/ml) than in wild-type
      (2.30 +/- 0.59, 5.26 +/- 0.67 ng/ml) rats, respectively. After beta-blockade,
      VT/VF episodes and mortality were similar in the two groups. The ETB-receptor
      decreases sympathetic activation and arrhythmogenesis during the early phase of
      MI, but these effects diminish during evolving MI.

PMID- 19838762
TI  - Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary
      hypertension rats.
AB  - Mesenchymal stem cells (MSCs) are the pluripotent cells, which enter the
      circulation and home to sites of tissue injury or inflammation. MSCs are
      highlighted as a potential cell vector for gene therapy. In this study, we
      investigated whether transplanted allogeneic MSCs preferentially accumulate in
      the lung in rats with pulmonary hypertension (PH) and if so to determine the
      efficacy of MSC-based prostacyclin synthase (PCS) gene therapy for PH. PH was
      induced in Lewis rats by injecting monocrotaline at 7-weeks-old (week 0). MSCs
      were obtained by culturing bone marrow mononuclear cells. Allogeneic MSCs were
      intravenously transplanted at week 2 when moderate PH had been established. PH
      enhanced indium-111-oxine-labeled MSC accumulation in the lungs, but not in other
      organs, 2.5-times and 6-times, 1 and 14 days after transplantation, respectively.
      Transplantation of MSCs transduced with PCS (PSC-MSCs), but not with GFP (GFP
      MSCs), reduced PH, pulmonary arterial thickening, and RV hypertrophy at week 4.
      The lung prostacyclin production was impaired in PH rats, which was restored and
      maintained for long time by PCS-MSCs, but not by GFP-MSCs. The survival rate at
      week 7 was 100% in PCS-MSC-transplanted PH rats, whereas they were 38 and 44% in
      PH rats and GFP-MSC-transplanted PH rats, respectively. In conclusion, the gene
      engineered MSCs would be a suitable cell vector for gene delivery specifically to
      the PH lung. The allogeneic PCS-MSC transplantation attenuated PH and
      cardiovascular remodeling, and improved the prognosis in PH rats. The MSC-based
      PCS gene therapy may be a promising strategy for PH treatment.

PMID- 19838764
TI  - The proof of efficacy in psychopharmacology: clinical studies, metaanalysis and
      evidence-based medicine.

PMID- 19838765
TI  - Differences between men and women in the course of opiate dependence: is there a
      telescoping effect?
AB  - According to the so-called telescoping effect, there is a gender-specific course
      of alcohol dependence with women starting alcohol use later than men and having a
      faster development of harmful consequences. There are inconsistent data regarding
      a telescoping effect in opiate dependence. In each of six European centres, 100
      opiate addicts were investigated by a structured interview (mainly the EuropASI
      and CIDI) at admission to various kinds of treatment (TREAT project). In a
      secondary analysis of the TREAT data, women and men were compared regarding age
      at onset of heroin use and the current severity of addiction. In addition, a
      comparison of female (n = 140) and male (n = 140) addicts matched for age and
      study centre were carried out. Eventually, multiple logistic and linear
      regressions were done with the interaction term of gender and time of regular
      consumption as predictor for the severity of dependence, besides, other
      sociodemographic variables. There was no difference between genders regarding the
      age at onset of regular heroin consumption. Up to 4 years of regular consumption,
      there are gender-specific differences in the course of opiate dependence, e.g. a
      faster progression of legal problems in men and social problems in women. There
      were no differences in the severity of dependence other than more economic
      problems for women. A telescoping effect could only partially be observed in this
      large sample of opiate addicts. A gender-specific course was limited to the first
      years of consumption, and included domains with a faster progression for men. It
      has to be assumed that opiate dependence is a rapidly developing disorder with
      early chronification. Afterwards, only individual courses with influences of the
      national treatment system were observed.

PMID- 19838767
TI  - Beevor's sign in facioscapulohumeral muscular dystrophy: an old sign with new
      implications.
AB  - Beevor's sign, an upward deflection of the umbilicus on flexion of the neck, is
      the result of paralysis of the inferior portion of the rectus abdominis muscle,
      so that the upper fibers predominate, pulling the umbilicus upwards. The
      condition may be caused by spinal cord injury at or below the level of Th10. It
      has also been observed in patients with facioscapulohumeral muscular dystrophy
      (FSHD). Positive Beevor's sign has been described as a sign of more than 90%
      sensitivity and specificity with regard to diagnosis of FSHD. We investigated 28
      patients with FSHD, proven by genetic analysis, and 65 non-FSHD patients with
      other neuromuscular diseases. In 13 patients classical FSHD phenotype was
      observed, in 15 patients phenotype was atypical. Beevor's sign was positive in 15
      out of 28 FSHD patients as well as in two of the 65 non-FSHD patients. In
      patients with typical FSHD phenotype, Beevor's sign was positive in 11/13. Only
      4/15 patients with atypical FSHD phenotype showed Beevor's sign. Beevor's sign is
      less frequent in patients with atypical phenotype. Although Beevor's sign is
      significantly more frequent in FSHD patients than in patients with other
      neuromuscular diseases, Beevor's sign is not as sensitive as previously reported.
      However, especially in atypical cases, Beevor's sign might help in the diagnosis
      of FSHD.

PMID- 19838763
TI  - Evidence-based medicine in psychopharmacotherapy: possibilities, problems and
      limitations.
AB  - Psychopharmacotherapy should now be regulated in the sense of evidence-based
      medicine, as is the case in other areas of clinical treatment in medicine. In
      general this is a meaningful development, which principally will have a positive
      impact on routine health care in psychiatry. But several related problems should
      not be ignored. So far consensus on an internationally accepted evidence
      graduation could not be reached due to several difficulties related to this. For
      example, focussing on the results of meta-analyses instead of considering
      relevant single studies results in a decision-making logic which is in conflict
      with the rationale applied by drug authorities in the licensing process. Another
      example is the relevance of placebo-controlled trials: if randomized placebo
      controlled phase-III studies are prioritized in the evidence grading, the
      evidence possibly deviates too far from the conditions of routine clinical care
      due to the special selection of patients in those studies. However, a grading
      primarily based on active comparator trials could lead to wrong conclusions about
      efficacy. This concerns especially the so-called "effectiveness" studies and
      other forms of phase-IV studies with their less restrictive methodological
      rigidity. Attempts to regulate psychopharmacotherapy in the sense of evidence
      based medicine come closer to their limits the more complex the clinical
      situation and the respective decision-making logic are. Even in times of evidence
      based medicine a large part of complex clinical decision-making in
      psychopharmacotherapy still relies more on clinical experience and a consensus on
      clinical experience, traditions and belief systems than on results of efficacy
      oriented phase-III and effectiveness-oriented phase-IV clinical studies.

PMID- 19838768
TI  - Comparison between rebinning methods and geometric re-projection for the
      estimation of missing oblique data in 3D-PET.
AB  - OBJECTIVE: Classically, the missing portions in the oblique projection data
      acquired from cylindrical scanners are synthesized by forward projecting an
      estimation of the activity computed from non-oblique data. Another quick and
      powerful way to perform the estimation of the truncated portions consists in
      applying Fourier rebinning methods. This paper intends to compare the
      performances of 3D geometric re-projection versus two Fourier rebinning
      techniques (iterative FOREPROJ and extended FORE) designed for re-projection.
      METHODS: Both analytical and noisy 3D projection data corresponding to a phantom
      constituted of warm and cold ellipsoids over a uniform background are simulated
      numerically for the SIEMENS Hi-Rez scanner. The object is reconstructed using 3D
      filtered back-projection. A prior estimation of the missing oblique data is
      performed using the three algorithms. RESULTS: The resolution properties and
      noise behavior of the three methods are compared and demonstrate a significant
      signal to noise ratio improvement using rebinning-based algorithms. CONCLUSIONS:
      We show that iterative FOREPROJ provides projection data with high accuracy 60%
      less time than geometric re-projection.

PMID- 19838769
TI  - Favorable coagulation profile with fondaparinux after hip surgery in elderly
      patients.
AB  - Twenty-three patients with fondaparinux prophylaxis over 75 years of age who
      underwent hip fracture surgery were enrolled in the study. Fondaparinux sodium
      (2.5 mg) was administered subcutaneously 6 h postoperatively and then every 24 h
      for 28 days. Coagulation and inflammatory parameters were measured
      preoperatively, then 10 h, 2, 7, and 28 days postoperatively. Increased D-dimers,
      positive acute phase proteins, and IL-6, and decreased negative acute phase
      proteins were observed preoperatively (P < 0.05). Maximum values were reached 10
      h postoperatively for IL-6 and D-dimer, and on postoperative days 2 and 7 for
      positive acute phase proteins (P < 0.05). Transferrin, prealbumin and
      antithrombin levels were lowest 10 h postoperatively and on postoperative day 2
      (P < 0.05). Increased D-dimers, IL-6, and positive acute phase proteins, and
      decreased negative acute phase proteins persisted until postoperative day 28 (P <
      0.05). Prothrombin fragments (F1 + 2) reached peak levels preoperatively and
      decreased gradually until postoperative day 28. Fondaparinux promoted the
      inhibition of thrombin generation, as documented by negative correlation between
      F1 + 2 and FXa inhibition (r = -0.46; P < 0.001). Fondaparinux-induced FXa
      inhibition increased gradually until postoperative day 28. This increase
      correlated positively with antithrombin activity (r = 0.4; P < 0.05).
      Fondaparinux prophylaxis counteracted pro-thrombogenic effect associated with hip
      fracture and subsequent surgery without severe bleeding complications.

PMID- 19838770
TI  - Newer anticoagulants in 2009.
AB  - Several newer anticoagulants are under clinical development. Recently two of
      them, Dabigatran etexilate/Pradaxa. and Rivaroxaban/Xarelto obtained marketing
      authorization in Europe and Canada for the prevention of thromboembolic events
      following major orthopedic surgery such as total hip and knee replacement. The
      results of Phase III clinical studies in thromboprophylaxis in major orthopedic
      surgery are highlighted and discussed in detail. Ongoing Phase II and III
      clinical trials assess their efficacy in the secondary prevention and treatment
      of deep vein thrombosis and pulmonary embolism, and in the long-term prevention
      of stroke in patients with non-valvular atrial fibrillation and in combination
      with aspirin and clopidogrel in patients with acute coronary syndromes. Many
      other small antithrombotic molecules including a new generation of low molecular
      weight heparins, are currently in different stages of clinical development. In
      addition to being administered orally, the newer anticoagulant agents have a more
      balanced benefit/risk ratio and wider therapeutic window. They have a rapid onset
      of action, a predictable anticoagulant effect that does not require routine
      laboratory monitoring. They have minor food and drug interactions, including
      those with cytochrome P450 and P.gp. They are highly specific and targeted to a
      single coagulation factor, and could carry similar or less hemorrhagic risks
      compared to the older anticoagulant agents. Finally, they may be used in a
      broader variety of patients, especially the medically ill patients with advanced
      cancer, and the elderly without any dosage adjustment, regardless of the patient
      age, gender, body weight, or in patients with mild renal impairment. Their use in
      the general world will hopefully confirm the promising results of clinical
      trials.

PMID- 19838772
TI  - Stability of poly(ethylene glycol)-graft-polyethylenimine copolymer/DNA
      complexes: influences of PEG molecular weight and PEGylation degree.
AB  - Polyethylenimine (PEI) is one of the most widely investigated cationic polymers
      for gene delivery. However, PEI/DNA complexes are unstable and tend to aggregate.
      PEGylation was used to improve the stability. The stability of polymer/DNA
      complexes was investigated including complexation stability, aggregation
      stability, sedimentation stability, and nuclease stability. PEI25K/DNA complexes
      were liable to aggregate to large particles (500-700 nm). The aggregation was
      proved to be induced by phosphate anion. In the medium without phosphate anion,
      aggregation was prevented by electrostatic repulsion. Owing to more efficient
      steric repulsion, PEG2 and PEG5K excelled PEG750 in facilitating copolymers to
      form stable small polyplexes (below 100 nm) without aggregation regardless of
      phosphate anion. The steric repulsion predominated over electrostatic repulsion
      in stabilization.

PMID- 19838773
TI  - A colorimetric and ratiometric fluorescent chemosensor for fluoride based on
      proton transfer.
AB  - N-Phenyl-N'-(3-quinolinyl)urea (1) has been developed as a highly selective
      colorimetric and ratiometric fluorescent chemosensor for fluoride ion based on a
      proton transfer mechanism. Evidences for the mechanism were provided by UV-vis
      and fluorescence titration and especially (1)H and (19)F NMR experiments. The
      sensor gave the largest ratiometric fluorescent response reported so far
      (R(max)/R(min) = 2620) to fluoride. Taking H(+) as the "recovering reagent", the
      sensor can be reversibly "used" and "recovered" for several cycles with only a
      slight decay of the response ability.

PMID- 19838774
TI  - Long-term cerebrospinal fluid and blood lymphocyte dynamics after rituximab for
      pediatric opsoclonus-myoclonus.
AB  - INTRODUCTION: Opsoclonus-myoclonus syndrome (OMS) is an autoimmune paraneoplastic
      disorder characterized by B and T cell abnormalities in cerebrospinal fluid (CSF)
      and propensity for relapse. The study aim was to assess whether rituximab-induced
      B cell ablation in CSF outlasts repopulation in blood and if there are changes in
      other lymphocyte subsets. MATERIALS AND METHODS: In 25 children with OMS, the
      expression of CSF and blood lymphocyte surface antigens was evaluated by flow
      cytometry before and at intervals after rituximab therapy. RESULTS: The reduction
      in CSF CD27+ memory, CD38+ activated, CD5+, and other B cell subsets was profound
      (p < 0.0001), comparable across groups (-94%), and sustained over 12-18 months
      despite repopulation in blood. The observed lag in memory B cell pool recovery in
      the CSF compared to peripheral blood may be clinically relevant. T cell
      phenotypic changes involved frequency, not absolute counts, and were transient.
      Co-treatment with IVIg or ACTH did not significantly alter B cell depletion or
      repletion. DISCUSSION: These data indicate that rituximab affords long-term
      protection against CSF B cell expansion in OMS (ClinicalTrials.gov NCT00244361).

PMID- 19838775
TI  - Coaches' attitudes and involvement in alcohol prevention among high school
      athletes.
AB  - A total of 288 high school coaches completed a survey on their attitudes toward
      and involvement in alcohol prevention among male high school athletes. Results
      indicated that coaches felt alcohol use was less of a problem among high school
      student-athletes than high school students in general. Only one-third of coaches
      (39%) worked at a school requiring them to talk to their athletes about alcohol
      use. Coaches most likely to be involved in alcohol prevention were those who had
      attended an alcohol prevention class/workshop and those who worked for schools
      with strong alcohol prevention policies and schools that required them to talk
      with athletes about alcohol use.

PMID- 19838776
TI  - Computational structure models of apo and diferric transferrin-transferrin
      receptor complexes.
AB  - Complexation of transferrin (Tf) and its receptor (TfR) is an essential event for
      iron uptake by the cell. Much data has been accumulated regarding Tf-TfR
      complexation, such as results from mutagenesis. We created 3D structural models
      of apo-human Tf-TfR (apoTf-TfR) and Fe(III)(2)Tf-TfR (Fe(2)Tf-TfR) complexes by
      computational rigid body refinement. The models are consistent with published
      mutagenesis experiments. In our models, the C-lobes of apoTf and Fe(2)Tf bind to
      the helical domain of TfR, and the N-lobes are sandwiched between the ectodomain
      of TfR and the cell membrane as previously reported. Further, the molecules of
      apoTf and Fe(2)Tf are not forced to undergo large conformational changes upon
      complexation. The creation of the models led a new and important finding that a
      residue of TfR, R651, which is called a hot spot for Tf-TfR binding, interacts
      with Tf E385 when either apoTf or Fe(2)Tf bind to TfR. The models rationally
      interpret the iron release from Fe(2)Tf-TfR upon acidification, dissociation of
      apoTf from TfR at slightly alkaline pH, and metal specific recognition of TfR.

PMID- 19838777
TI  - Smoking among pregnant women with Medicaid insurance: are mental health factors
      related?
AB  - Smoking during pregnancy is the single most modifiable risk factor for poor birth
      outcomes, yet it remains prevalent among low-income women. This study examined
      factors associated with continued smoking and quitting among pregnant women. A
      total of 2,203 Medicaid-eligible pregnant women were screened at their first
      enhanced prenatal services visit for risk factors including demographics, health
      behaviors (smoking, alcohol and drug use), mental health (history of mental
      health disorders, current depressive symptoms), and stress. Smoking status was
      divided into non-smokers, quitters (quit smoking since learning of pregnancy),
      and continuing smokers. Descriptive statistics and logistic regression models
      were used to describe the sample and analyze relationships between smoking status
      and other characteristics. Overall, 57% were non-smokers, 17% quitters, and 26%
      continuing smokers. Approximately 18% had severe depressive symptoms, 53% had a
      high stress score, and 33% had a history of mental health problems. Younger women
      had lower odds of continued smoking as compared to both non-smokers (OR = 0.48, p
      < 0.01) and quitters (OR = 0.56, p < 0.05). Older women with less than a 12th
      grade education had higher odds of continued smoking (OR = 2.17, p < 0.01) and
      quitting (OR = 1.62, p < 0.05) as compared to non-smokers. Alcohol use (OR =
      2.81, p < 0.05) and drug use before pregnancy (OR = 5.32, p < 0.01) predicted
      continued smoking compared to non-smoking. Women with a mental health history (OR
      = 1.81, p < 0.01) and high stress scores (OR = 1.39, p < 0.05) had higher odds of
      continued smoking compared to non-smokers. Mental health history, stress,
      demographics, current alcohol and past drug use are strongly related to continued
      smoking in this population.

PMID- 19838778
TI  - Agreement between self-report and birth certificate for gestational diabetes
      mellitus: New York State PRAMS.
AB  - This study examined agreement (concordance or convergent validity) between self
      report and birth certificate for gestational diabetes. Study population was 2,854
      women who had live births 2-6 months earlier and responded to a questionnaire
      from the New York State Pregnancy Risk Assessment Monitoring System (PRAMS)
      survey, 2004-2006. Agreement between self-report and birth certificate was
      assessed for the study population overall, and for subgroups defined by race,
      age, education, marital status, number of previous live births, time of first
      prenatal care, and birth weight of the newborn. A total of 258 women self
      reported gestational diabetes, while birth certificates indicated that 138 women
      had gestational diabetes. For the study population overall, percent agreement was
      93.8% and Kappa was 0.53. Due to the moderate bias index (68.2% overall, ranged
      from 33.3 to 100% in subgroups) and the high skewed prevalence index (91.8%
      overall, ranged from 70.7 to 97.5% in subgroups), we determined Prevalence
      Adjusted and Bias-Adjusted Kappa (PABAK) was a better measure of agreement. PABAK
      was 0.88 overall, indicating very good agreement. PABAK was uniformly high in all
      subgroups. The highest PABAK was found among women aged 25 years and younger
      (0.93), and the lowest PABAK was among Asian women (0.79). Although the absence
      of a gold standard for gestational diabetes hinders assessment of criterion
      validity, high PABAK measures suggest that self-reporting by PRAMS respondents is
      feasible for identifying cases of gestational diabetes for surveillance and
      population-based epidemiologic research.

PMID- 19838779
TI  - A proteomic analysis of the ventral hippocampus of rats subjected to maternal
      separation and escitalopram treatment.
AB  - Early life stress is known to predispose humans to the development of depression.
      Developmental stress has been shown to cause various changes in neurotransmitter
      systems, neurotrophin expression and the hypothalamic pituitary adrenal-axis in
      the rat brain. The aim of this study was to identify which cytosolic proteins are
      altered by maternal separation, as a model for depression, as well as by chronic
      antidepressant treatment. Rats were maternally separated from postnatal day 2-14
      for 3 h per day while control rats were normally reared. Both groups were divided
      and received either escitalopram or saline injections for 6 weeks starting from
      postnatal day 40. The ventral hippocampal tissue was fractionated and the
      cytosolic fraction used for 2-D-gel electrophoresis and liquid chromatography
      coupled to mass spectrometry analyses to identify peptides. Mascot database
      searches were done to identify proteins that were differentially expressed
      between the groups. Proteins that were significantly changed by maternal
      separation included amongst others: molecular chaperones and proteins related to
      energy metabolism; neuroplasticity; oxidative stress regulation; and protein
      metabolism. Treatment with escitalopram, a selective-serotonin reuptake
      inhibitor, induced changes in a different group of proteins, except for a few
      involved in energy metabolism and neuroprotective pathways. The results indicate
      which cytosolic proteins are changed by early life stress and may therefore be
      involved in the development of depression.

PMID- 19838781
TI  - Why Japanese workers remain in the labor force so long: lessons for the United
      States?
AB  - As part of the search for ways to increase labor force participation rates among
      older workers in the United States, it makes sense to take a close look at
      evidence from Japan, one of the few industrial countries with a substantially
      higher labor force participation rate among older workers, particularly men, than
      the United States. Based mainly on prior studies and original interview data, we
      first discuss five potential factors which help explain why Japanese workers
      remain in the labor force as long as they do: (1) perceived economic necessity;
      (2) the large fraction of workers who are self-employed; (3) a culture that puts
      a high value on remaining in the labor force throughout the life course; (4) the
      long healthy life expectancy; and (5) the government's role in facilitating the
      labor force participation of older workers. We suggest that the Japanese national
      cultural value on remaining economically productive well into old age clearly
      underlies the development of the government's legislative initiatives aiming to
      extend the working lives of older workers. We then outline three policy
      suggestions for those seeking to increase labor force participation rates among
      older U.S. workers: (1) increase the financial incentive to workers who remain in
      the labor force; (2) improve public programs designed to foster efforts by older
      workers to become self-employed; and (3) increase the extent of government
      efforts to link older workers to prospective employers.

PMID- 19838780
TI  - The effect of epigallocatechin gallate on lipopolysaccharide-induced acute lung
      injury in a murine model.
AB  - This study was performed to evaluate the effects of epigallocatechin 3 gallate
      (EGCG) on lipopolysaccharide (LPS)-induced acute lung injury in a murine model.
      In the present study, production of TNF-alpha and MIP-2 and activation of
      extracellular signal-regulated kinases (ERK)1/2, c-Jun amino terminal kinases
      (JNK) and p38 in RAW264.7 cells were measured. EGCG inhibited the production of
      TNF-alpha and MIP-2, and attenuated phosphorylation levels of ERK1/2 and JNK, but
      not p38 in RAW264.7 cells stimulated with LPS. Also, EGCG attenuated the
      production of TNF-alpha and MIP-2, and the phosphorylation of ERK1/2 and JNK in
      the lungs of mice administered with LPS intratracheally. It reduced wet/dry
      weight ratio, histological severities, and neutrophil accumulation in the lungs
      in mice given LPS. Our results showed that EGCG attenuated LPS-induced lung
      injury by suppression of the MIP-2 and TNF-alpha production, and ERK1/2 and JNK
      activation in macrophage stimulated with LPS.

PMID- 19838782
TI  - Mortality in autism: a prospective longitudinal community-based study.
AB  - The purposes of the present study were to establish the mortality rate in a
      representative group of individuals (n = 120) born in the years 1962-1984,
      diagnosed with autism/atypical autism in childhood and followed up at young adult
      age (>or=18 years of age), and examine the risk factors and causes of death. The
      study group, which constituted a total population sample of children with these
      diagnoses, were followed up in Swedish registers. Nine (7.5%) of the 120
      individuals with autism had died at the time of follow-up, a rate 5.6 times
      higher than expected. The mortality rate was significantly higher among the
      females. Associated medical disorders (including epilepsy with cognitive
      impairment) and accidents accounted for most of the deaths, and it was not
      possible to determine whether autism "per se" actually carries an increased
      mortality risk.

PMID- 19838784
TI  - The DSM diagnostic criteria for gender identity disorder in adolescents and
      adults.
AB  - Apart from some general issues related to the Gender Identity Disorder (GID)
      diagnosis, such as whether it should stay in the DSM-V or not, a number of
      problems specifically relate to the current criteria of the GID diagnosis for
      adolescents and adults. These problems concern the confusion caused by
      similarities and differences of the terms transsexualism and GID, the inability
      of the current criteria to capture the whole spectrum of gender variance
      phenomena, the potential risk of unnecessary physically invasive examinations to
      rule out intersex conditions (disorders of sex development), the necessity of the
      D criterion (distress and impairment), and the fact that the diagnosis still
      applies to those who already had hormonal and surgical treatment. If the
      diagnosis should not be deleted from the DSM, most of the criticism could be
      addressed in the DSM-V if the diagnosis would be renamed, the criteria would be
      adjusted in wording, and made more stringent. However, this would imply that the
      diagnosis would still be dichotomous and similar to earlier DSM versions. Another
      option is to follow a more dimensional approach, allowing for different degrees
      of gender dysphoria depending on the number of indicators. Considering the strong
      resistance against sexuality related specifiers, and the relative difficulty
      assessing sexual orientation in individuals pursuing hormonal and surgical
      interventions to change physical sex characteristics, it should be investigated
      whether other potentially relevant specifiers (e.g., onset age) are more
      appropriate.

PMID- 19838785
TI  - Queer diagnoses: parallels and contrasts in the history of homosexuality, gender
      variance, and the diagnostic and statistical manual.
AB  - The American Psychiatric Association (APA) is in the process of revising its
      Diagnostic and Statistical Manual (DSM), with the DSM-V having an anticipated
      publication date of 2012. As part of that ongoing process, in May 2008, APA
      announced its appointment of the Work Group on Sexual and Gender Identity
      Disorders (WGSGID). The announcement generated a flurry of concerned and anxious
      responses in the lesbian, gay, bisexual, and transgender (LGBT) community, mostly
      focused on the status of the diagnostic categories of Gender Identity Disorder
      (GID) (for both children and adolescents and adults). Activists argued, as in the
      case of homosexuality in the 1970s, that it is wrong to label expressions of
      gender variance as symptoms of a mental disorder and that perpetuating DSM-IV
      TR's GID diagnoses in the DSM-V would further stigmatize and cause harm to
      transgender individuals. Other advocates in the trans community expressed concern
      that deleting GID would lead to denying medical and surgical care for transgender
      adults. This review explores how criticisms of the existing GID diagnoses
      parallel and contrast with earlier historical events that led APA to remove
      homosexuality from the DSM in 1973. It begins with a brief introduction to binary
      formulations that lead not only to linkages of sexual orientation and gender
      identity, but also to scientific and clinical etiological theories that
      implicitly moralize about matters of sexuality and gender. Next is a review of
      the history of how homosexuality came to be removed from the DSM-II in 1973 and
      how, not long thereafter, the GID diagnoses found their way into DSM-III in 1980.
      Similarities and differences in the relationships of homosexuality and gender
      identity to psychiatric and medical thinking are elucidated. Following a
      discussion of these issues, the author recommends changes in the DSM-V and some
      internal and public actions that the American Psychiatric Association should
      take.

PMID- 19838786
TI  - Mental health risk and social ecological variables associated with educational
      attainment for gulf war veterans: implications for veterans returning to civilian
      life.
AB  - This study examines how post-secondary educational attainment among young
      veterans of the first gulf war affects their mental health status. The all
      volunteer military attracts recruits by offering them veterans' educational
      benefits. Education should help veterans adjust to civilian life. Few studies
      have shown whether education following military service helps improve veterans'
      mental health, however. Viewing resiliency, life span and life course, and social
      geography theories through the lens of social ecology, it is hypothesized that
      selected contextual factors in the personal, interpersonal, and organizational
      domains could mediate or moderate the relationship between education and
      veterans' mental health. Informational social networks showed an association with
      obtaining mental illness treatment. Recent treatment for post-traumatic stress
      disorder (PTSD) showed an association with use of veterans' educational benefits.
      Residing with a small nuclear family in conjunction with having higher levels of
      health and educational benefits and a higher family income was associated with
      higher educational attainment.

PMID- 19838783
TI  - The biological properties of E6 and E7 oncoproteins from human papillomaviruses.
AB  - More than 100 different human papillomavirus (HPV) types have been isolated so
      far, and they can be sub-grouped in cutaneous or mucosal according to their
      ability to infect the skin or the mucosa of the genital or upper-respiratory
      tracts. A sub-group of human mucosal HPVs, referred to as high-risk HPV types, is
      responsible for approximately 5% of all human cancers, which represents one-third
      of all the tumours induced by viruses. Epidemiological and biological studies
      have shown that HPV16 is the most oncogenic type within the high-risk group.
      Emerging lines of evidence suggest that, in addition to the high-risk mucosal HPV
      types, certain cutaneous HPVs are involved in skin cancer. HPV-associated cancers
      are intimately linked to HPV persistence and the accumulation of chromosomal
      rearrangements. The products of the early genes, E6 and E7, of the high-risk
      mucosal HPV types play a key role in both events. Indeed, these proteins have
      developed a number of strategies to evade host immuno-surveillance allowing viral
      persistence, and to alter cell cycle and apoptosis control, facilitating the
      accumulation of DNA damage/mutations. Often, the two oncoproteins target the same
      cellular pathways with different mechanisms, showing a strong synergism in
      promoting cellular transformation and neutralizing the immune response. Here, we
      review most of the findings on the biological properties and molecular mechanisms
      of the oncoproteins E6 and E7 from mucosal and cutaneous HPV types.

PMID- 19838787
TI  - Increases in tolerance within naturalistic, intentional communities: a
      randomized, longitudinal examination.
AB  - The authors examine differential changes in values of tolerance among 150
      participants discharged from inpatient treatment centers, and randomly assigned
      to either a self-help-based, communal living setting (i.e., Oxford House), or
      usual aftercare. Participants were interviewed every 6 months for a 24-month
      period. Hierarchical linear modeling (HLM) was used to examine the effect of
      condition (therapeutic communal living versus usual aftercare) on wave
      trajectories of tolerance (i.e., universality/diversity scores). Over time,
      residents of the communal living model demonstrated significantly greater values
      of tolerance than usual aftercare participants. Communal living participants who
      resided in the house for over 6 months showed the most substantial increases in
      tolerance. Results support the notion that communal living residents may develop
      more tolerant attitudes by striving toward superordinate community goals
      (objectives held by (a) the whole group and (b) which individual members could
      not achieve alone).

PMID- 19838788
TI  - Multiple psychological senses of community in Afghan context: exploring
      commitment and sacrifice in an underground resistance community.
AB  - The study of positive outcomes associated with strong psychological sense of
      community (PSOC) has grown worldwide. Yet most research explores PSOC as a uni
      dimensional (positive) variable operating in a single referent community.
      Theoretical and empirical literature has suggested, however, that PSOC can be
      positive, neutral or negative (Brodsky in J Commun Psychol 24(4):347-363, 1996;
      Brodsky et al. in Psychological sense of community: Research, applications and
      implications. Kluwer, New York 2002) and since people live in multiple physical
      and relational communities, there may be multiple PSOCs (M-PSOC) operating
      simultaneously and interactively (Brodsky and Marx in J Commun Psychol 29(2):1
      18, 2001). This paper explores the operation of M-PSOC in the lives of Afghan
      women, and male supporters, who belonged to a resistance organization before,
      during and after the Taliban regime. Decisions to join and stay in this community
      can be explained, in part, through the differentiation of positive,
      organizational-level PSOC from negative, macro-community-level PSOC. In addition,
      M-PSOC suggests unique cultural meanings of the terms "community" and "choice."
      Findings have implications for cross-cultural community work and for fostering
      resilient sub-communities in the face of macro and societal-level risks and
      oppression.

PMID- 19838789
TI  - Local food environments: they're all stocked differently.
AB  - The obesity epidemic has widened the aims of prevention research to include the
      influence of local food environments on health outcomes. This mixed methods study
      extends existing research focused on local food environments by examining whether
      community members' find food accessible. Data from food store audits and one-on
      one interviews were analyzed. Results reveal that most of the food stores
      surrounding the three research sites were convenience stores and non-chain
      grocery stores; interviewees did not perceive these stores to be "real" food
      stores. Tobacco and alcohol products were more prevalent in the food stores than
      all varieties of milk, fresh fruits, or fresh vegetables. Food access varied by
      site in a manner that was designed to appeal to customers' race, class, gender,
      or environment. Findings reveal that local food environments are reflections of
      social hierarchies. Unraveling the politics of space ought to be a part of
      broader efforts to promote the public's health.

PMID- 19838790
TI  - A social ecological conceptual framework for understanding adolescent health
      literacy in the health education classroom.
AB  - With the rising concern over chronic health conditions and their prevention and
      management, health literacy is emerging as an important public health issue. As
      with the development of other forms of literacy, the ability for students to be
      able to access, understand, evaluate and communicate health information is a
      skill best developed during their years of public schooling. Health education
      curricula offer one approach to develop health literacy, yet little is known
      about its influence on neither students nor their experiences within an
      educational context. In this article, we describe our experience applying a
      social ecological model to investigating the implementation of a health education
      curriculum in four high schools in British Columbia, Canada. We used the model to
      guide a conceptual understanding of health literacy, develop research questions,
      select data collection strategies, and interpret the findings. Reflections and
      recommendations for using the model are offered.

PMID- 19838791
TI  - Examining the etiology of childhood obesity: The IDEA study.
AB  - The prevalence of childhood obesity is of great public health concern. A social
      ecological framework that is transdisciplinary and multilevel by nature is
      recognized as the most promising approach for studying this problem. The purpose
      of this paper is to describe longitudinal research using a social ecological
      framework to study the etiology of childhood obesity. Individual and contextual
      factors are assessed in a cohort of youth and their parents including
      psychosocial factors, and home, school and neighborhood environments. The
      conceptual model guiding the research and the study design and measures used to
      operationalize the factors in the model and the descriptive characteristics of
      the baseline sample of youth and parents enrolled in the research are presented.
      The use of a conceptual model to guide the research, a transdisciplinary
      approach, a longitudinal cohort design and state-of-the-art measures of the
      individual and the environment are strengths of this research.

PMID- 19838792
TI  - Researching a local heroin market as a complex adaptive system.
AB  - This project applies agent-based modeling (ABM) techniques to better understand
      the operation, organization, and structure of a local heroin market. The
      simulation detailed was developed using data from an 18-month ethnographic case
      study. The original research, collected in Denver, CO during the 1990s,
      represents the historic account of users and dealers who operated in the Larimer
      area heroin market. Working together, the authors studied the behaviors of
      customers, private dealers, street-sellers, brokers, and the police, reflecting
      the core elements pertaining to how the market operated. After evaluating the
      logical consistency between the data and agent behaviors, simulations scaled-up
      interactions to observe their aggregated outcomes. While the concept and findings
      from this study remain experimental, these methods represent a novel way in which
      to understand illicit drug markets and the dynamic adaptations and outcomes they
      generate. Extensions of this research perspective, as well as its strengths and
      limitations, are discussed.

PMID- 19838793
TI  - Sequence and timing of three community interventions to domestic violence.
AB  - Community responses to domestic violence typically involve the introduction of
      multiple interventions. Yet very little is known about the impact of the timing
      and sequencing of these interventions on community outcomes. A reason for this is
      the inherent limitations of traditional methods in social science. New methods
      are needed to understand the effect of varying the sequence and timing of
      interventions. This study responds to the issue by introducing system dynamics as
      a method for modeling community interventions. The paper presents a model of
      domestic violence cases moving through a criminal justice response, and uses the
      simulation model to evaluate the impact of implementing three interventions
      mandatory arrest, victim advocacy, and changes in level of cooperation-on two
      system-level outcomes: improving offender accountability and increasing victim
      safety. Results illustrate the complex nature of these relationships.
      Implications for community practice and future research are also discussed.

PMID- 19838794
TI  - Area-based socioeconomic characteristics of industries at high risk for violence
      in the workplace.
AB  - This study examined socioeconomic factors associated with the presence of
      workplaces belonging to industries reported to be at high risk for worker
      homicide. The proportion of 2004 North Carolina workplaces in high-risk
      industries was computed following spatial linkage of individual workplaces to
      2000 United States Census Block Groups (n = 3,925). Thirty census-derived
      socioeconomic variables (selected a priori as potentially predictive of violence)
      were summarized using exploratory factor analysis into poverty/deprivation,
      human/economic capital, and transience/instability. Multinomial logistic
      regression models indicate associations between higher proportion of workplaces
      belonging to high-risk industries and Block Groups with more poverty/deprivation
      or transience/instability and less human/economic capital. The relationship
      between human/economic capital and Block Groups proportion of high-risk industry
      workplaces was modified by levels of transience/instability. Community
      characteristics therefore contribute to the potential for workplace violence, and
      future research should continue to understand the relationship between social
      context and workplace violence risk.

PMID- 19838795
TI  - African-American women's conceptualizations of health disparities: a community
      based participatory research approach.
AB  - Health disparities among African-American families represent a significant social
      problem. Nationally, African-American infants have dramatically worse birth
      outcomes than other racial and ethnic groups. A Community-Based Participatory
      Research approach was utilized to engage community residents. This study examined
      participants' definitions of infant mortality, views on the community impact of
      infant mortality, and strengths and vulnerabilities in the health care service
      delivery system. Qualitative data were gathered in a rural North Florida
      community where health education groups are conducted. Eight focus groups were
      arranged with African-American women (n = 46), ranging in age from 14 to 35, who
      were pregnant, parenting children under the age of two. Respondents poignantly
      described personal experiences of loss associated with infant mortality. They
      indicated awareness of problems related to lack of accessibility and availability
      of medical and social services. The use of social-ecological theory and
      implications for policy and social justice are discussed.

PMID- 19838797
TI  - The importance of the community context in the epidemiology of early adolescent
      substance use and delinquency in a rural sample.
AB  - Considerable research has demonstrated that substance use and delinquency during
      early adolescence can have long-term negative health consequences. As the
      correlates of these behaviors cross levels and contexts, it is likely that a
      social ecological approach will provide insight to inform community prevention.
      This approach informs the present study, which focuses on developing a multiple
      method measurement strategy to examine associations among community risks,
      resources, and rates of early adolescent substance use and delinquency in 28
      rural and small town communities. Measures include five domains of community
      risk, four domains of community resources, and population rates of early
      adolescent substance use and delinquency. Results demonstrated that several
      measures of context were significantly associated with community rates of
      adolescent substance use and delinquency, and different risks and resources
      appear important for different outcomes. Multiple associations were curvilinear,
      and interactions may also be important. Findings suggest that it may be
      worthwhile to create and test new intervention strategies that target community
      factors in the pursuit of prevention.

PMID- 19838798
TI  - Tunicamycin-induced cell death in the trigeminal ganglion is suppressed by nerve
      growth factor in the mouse embryo.
AB  - The effect of nerve growth factor (NGF) on tunicamycin (Tm)-treated neurons in
      the trigeminal ganglion was investigated by use of caspase-3
      immunohistochemistry. In intact embryos at embryonic day 16.5, only a few caspase
      3-immunoreactivity were detected in the ganglion neurons. Mean +/- SE of the
      density of the immunoreactivity was 0.22 +/- 0.03%. In contrast, the number of
      the immunoreactive neurons was increased at 24 h after injection of 0.5 microg Tm
      in 1 microl of 0.05 N NaOH solution into mouse embryos at embryonic day 15.5. The
      density of immunoreactivity was also increased (mean +/- SE = 1.44 +/- 0.11%)
      compared to intact and 0.05 N NaOH-treated embryos (mean +/- SE = 0.35 +/-
      0.03%). The Tm treatment caused increase of the number of trigeminal neurons
      representing apoptotic profiles (intact, mean +/- SE = 79.3 +/- 8.5; 0.05 N NaOH,
      mean +/- SE = 132 +/- 11.5; 0.5 microg Tm, mean +/- SE = 370.2 +/- 64.8). In
      addition, NGF significantly prevented the increase of density of the
      immunoreactivity (mean +/- SE = 0.54 +/- 0.16%) and the number of apoptotic cells
      (mean +/- SE = 146.2 +/- 11.3). Saline application (without NGF) had no effect on
      Tm-induced increase of the immunoreactivity (mean +/- SE = 1.78 +/- 0.23%) or the
      apoptotic profiles (mean +/- SE = 431.9 +/- 80.5). These results indicate that Tm
      induced cell death in the trigeminal ganglion is suppressed by NGF in the mouse
      embryo.

PMID- 19838800
TI  - Electrical concepts in the surface electromyographic signal.
AB  - There are frequently used electrical terms in the biofeedback literature. Often
      it is assumed that the reader has detailed knowledge of these terms. The
      difficulty begins when seemingly familiar terms are used as a basis for an in
      depth explanation of the process of electromyography. For example, the concept of
      impedance is based on three building blocks of electricity: current, voltage and
      resistance. The term "impedance" is found in every manual for biofeedback
      equipment with the suggestion that the electrode site be kept "low" and the
      encoder input "high". A little electrical knowledge can explain why this is so
      and in the process formulate a more thorough understanding of the equipment used
      everyday with a client.

PMID- 19838799
TI  - Diabetes alters aromatase enzyme levels in sciatic nerve and hippocampus tissues
      of rats.
AB  - Diabetes mellitus (DM) is associated with increased risk of impaired cognitive
      function. Diabetic neuropathy is one of the most common and important
      complications of DM. Estrogens prevent neuronal loss in experimental models of
      neurodegeneration and accelerate nerve regeneration. Aromatase catalyzes the
      conversion of androgens to estrogens and expressed in a variety of tissues
      including neurons. Although insulin is known to regulate the activity of
      aromatase there is no study about the effects of diabetes on this enzyme. Present
      study was designed to investigate the effects of experimental diabetes on
      aromatase expression in nervous system. Gender-based differences were also
      investigated. Rats were injected with streptozotocin to induce diabetes. At the
      end of 4 and 12 weeks sciatic nerve and hippocampus homogenates were prepared and
      evaluated for aromatase proteins. Aromatase expressions in sciatic nerves of both
      genders were decreased in 4 weeks of diabetes, but in 12 weeks the enzyme levels
      were increased in females and reached to control levels in male animals.
      Aromatase levels were not altered in hippocampus at 4 weeks but increased at 12
      weeks in female diabetic rats. No significant differences were observed at enzyme
      levels of hippocampus in male diabetic rats. Insulin therapy prevented all
      diabetes-induced changes. In conclusion, these results indicated for the first
      time that, DM altered the expression of aromatase both in central and peripheral
      nervous systems. Peripheral nervous system is more vulnerable to damage than
      central nervous system in diabetes. These effects of diabetes differ with gender
      and compensatory neuroprotective mechanisms are more efficient in female rats.

PMID- 19838801
TI  - Heart rate variability during sleep following the practice of cyclic meditation
      and supine rest.
AB  - Day time activities are known to influence the sleep on the following night.
      Cyclic meditation (CM) has recurring cycles. Previously, the low frequency (LF)
      power and the ratio between low frequency and high frequency (LF/HF ratio) of the
      heart rate variability (HRV) decreased during and after CM but not after a
      comparable period of supine rest (SR). In the present study, on thirty male
      volunteers, CM was practiced twice in the day and after this the HRV was recorded
      (1) while awake and (2) during 6 h of sleep (based on EEG, EMG and EGG
      recordings). This was similarly recorded for the night's sleep following the day
      time practice of SR. Participants were randomly assigned to the two sessions and
      all of them practiced both CM and SR on different days. During the night
      following day time CM practice there were the following changes; a decrease in
      heart rate, LF power (n.u.), LF/HF ratio, and an increase in the number of pairs
      of Normal to Normal RR intervals differing by more than 50 ms divided by total
      number of all NN intervals (pNN50) (P < 0.05, in all cases, comparing sleep
      following CM compared with sleep following SR). No change was seen on the night
      following SR. Hence yoga practice during the day appears to shift sympatho-vagal
      balance in favor of parasympathetic dominance during sleep on the following
      night.

PMID- 19838802
TI  - Prevalence of Axis II disorders in a sample of clients undertaking psychiatric
      evaluation for sex reassignment surgery.
AB  - The aim of the present study is to assess the prevalence of Axis II disorders
      (DSM-IV-TR) in a sample of clients requesting sex reassignment surgery (SRS),
      consecutively admitted to a Gender Identity Disorder (GID) psychiatric unit.
      Fifty clients self-referred as transsexuals (34 biological males and 16
      biological females; mean age = 31.74 +/- 7.06 years) were assessed through the
      SCID-II after a preliminary evaluation to exclude current major psychiatric
      disorders. Prevalence of any Axis II disorder was 52% (N = 26), with no
      significant differences related to biological sex. The most frequent personality
      disorders were Cluster B PDs (22% of total sample), followed by Cluster C (12%)
      and Cluster A PDs (2%). A significant prevalence of NOS PD (16%) was also found.
      Our data offers prevalence estimates slightly higher than those found in previous
      studies and does not provide evidence for any differences in the
      psychopathological profile and severity between MtF and FtM transsexuals.

PMID- 19838803
TI  - A comparative study of intracranial EEG files using nonlinear classification
      methods.
AB  - This study is a comparative evaluation of nonlinear classification methods with a
      focus on nonlinear decision functions and the standard method of support vector
      machines for seizure detection. These nonlinear classification methods are used
      on key features that were extracted on subdural EEG data after a thorough
      evaluation of all the frequency bands from 1 to 44 Hz. The sensitivity,
      specificity, and accuracy of seizure detection reveal that the gamma frequencies
      (36-44 Hz) are most suitable for detecting seizure files using a unique 2D
      decisional plane. We evaluated 157 intracranial EEG files from 14 patients by
      calculating the spectral power using nonoverlapping 1-s windows on different
      frequency bands. A key finding is in establishing a 2D decision plane, where
      duration of the seizure is used as the first dimension (x coordinate) and the
      maximum of the gamma frequency components is used as the second dimension (y
      coordinate). Within this 2D plane, the best results were observed when the
      nonlinearity degree is three for the proposed nonlinear decision functions, with
      a sensitivity of 96.3%, a specificity of 96.8%, and accuracy of 96.7%.

PMID- 19838804
TI  - Principle design and actuation of a dual chamber electromagnetic micropump with
      coaxial cantilever valves.
AB  - This paper deals with the design and characterization of an electromagnetic
      actuation micropump with superimposed dual chambers. An integral part of
      microfluidic system includes micropumps which have become a critical design focus
      and have the potential to alter treatment and drug delivery requirements to
      patients. In this paper, conceptual design of variable geometrical
      nozzle/diffuser elements, coaxial cantilever valve, is proposed. It takes
      advantages of cantilever fluctuating valves with preset geometry to optimize and
      control fluid flow. The integration of this conceptual valve into a dual chamber
      micropump has increased the flow rate when compared to a single chamber
      micropump. This technique also allows for the fluid flow to be actively
      controlled by adjusting the movement of the intermediate membrane and the
      cantilever valves due to their fast response and large deflection properties when
      subjected to an electromagnetic field. To ensure reliability and performance of
      both the membrane and electromagnets, finite element method was used to perform
      the stress-strain analysis and optimize the membrane structure and electromagnet
      configuration. The frequency-dependent flow rates and backpressure are
      investigated for different frequencies by varying the applied currents from 1A to
      1.75A. The current micropump design exhibits a backpressure of 58 mmH(2)O and has
      a water flow rate that reaches maximum at 1.985 ml/s under a 1.75A current with a
      resonance frequency of 45 Hz. This proposed micropump while at its initial
      prototype stage can satisfy the requirements of wide flow rate drug delivery
      applications. Its controllability and process design are attractive for high
      volume fabrication and low cost.

PMID- 19838805
TI  - Outcome of gonadotropin therapy for male infertility due to hypogonadotrophic
      hypogonadism.
AB  - Data on the management of male infertility secondary to hypogonadotrophic
      hypogonadism (HH) are limited. We report our extensive experience with
      intramuscular injections of gonadotropins, one of the two methods used for this
      purpose. Eighty-seven married men (median age, 28 years) with either congenital
      (47 men) or acquired (40 men) HH were treated for a median of 26 months (range, 6
      57) with intramuscular injections of gonadotropins (HCG/HMG) three times weekly
      for the purpose of achieving fertility. The outcome was assessed by achievement
      of one or more pregnancies. Of the 151 courses of HCG/HMG treatment administered
      to 87 patients, 85 courses (56.3%) were successful, resulting in 85 pregnancies
      (median pregnancy rate 2, range 1-10) in 35 patients (40%) while 52 cases did not
      achieve pregnancy. Responders had larger pretherapy testicular volume (9 +/- 3.6
      cc) compared to non-responders [(5.7 +/- 2.0 cc), P < 0.0001], but there was no
      difference in age, LH, FSH or testosterone levels or doses of HCG/HMG used. The
      pregnancy rate was similar in those with congenital (51.4%) and acquired causes
      (48.6%) of HH (P = 0.83). Only testicular size was predictive of conception (P <
      0.001, odds ratio 1.5, 95% CI 1.21-1.92) while age, pretherapy levels of
      testosterone, LH, FSH and doses of HCG/HMG did not predict the success of
      pregnancy. Gonadotropins are moderately effective in achieving one to several
      pregnancies in HH. Only testicular size is predictive of success in achieving
      pregnancy. There is no difference in success between those with congenital and
      acquired causes of HH.

PMID- 19838806
TI  - Access to adequate outpatient depression care for mothers in the USA: a
      nationally representative population-based study.
AB  - Maternal depression is often untreated, resulting in serious consequences for
      mothers and their children. Factors associated with receipt of adequate treatment
      for depression were examined in a population-based sample of 2,130 mothers in the
      USA with depression using data from the 1996-2005 Medical Expenditure Panel
      Survey. Chi-squared analyses were used to evaluate differences in
      sociodemographic and health characteristics by maternal depression treatment
      status (none, some, and adequate). Multivariate regression was used to model the
      odds of receiving some or adequate treatment, compared to none. Results indicated
      that only 34.8% of mothers in the USA with depression received adequate
      treatment. Mothers not in the paid workforce and those with health insurance were
      more likely to receive treatment, while minority mothers and those with less
      education were less likely to receive treatment. Understanding disparities in
      receipt of adequate treatment is critical to designing effective interventions,
      reducing treatment inequities, and ultimately improving the mental health and
      health of mothers and their families.

PMID- 19838808
TI  - Periodic solutions of piecewise affine gene network models with non uniform decay
      rates: the case of a negative feedback loop.
AB  - This paper concerns periodic solutions of a class of equations that model gene
      regulatory networks. Unlike the vast majority of previous studies, it is not
      assumed that all decay rates are identical. To handle this more general
      situation, we rely on monotonicity properties of these systems. Under an
      alternative assumption, it is shown that a classical fixed point theorem for
      monotone, concave operators can be applied to these systems. The required
      assumption is expressed in geometrical terms as an alignment condition on so
      called focal points. As an application, we show the existence and uniqueness of a
      stable periodic orbit for negative feedback loop systems in dimension 3 or more,
      and of a unique stable equilibrium point in dimension 2. This extends a theorem
      of Snoussi, which showed the existence of these orbits only.

PMID- 19838807
TI  - Protein structure calculation with data imputation: the use of substitute
      restraints.
AB  - The amount of experimental restraints e.g., NOEs is often too small for
      calculating high quality three-dimensional structures by restrained molecular
      dynamics. Considering this as a typical missing value problem we propose here a
      model based data imputation technique that should lead to an improved estimation
      of the correct structure. The novel automated method implemented in AUREMOL makes
      a more efficient use of the experimental information to obtain NMR structures
      with higher accuracy. It creates a large set of substitute restraints that are
      used either alone or together with the experimental restraints. The new approach
      was successfully tested on three examples: firstly, the Ras-binding domain of
      Byr2 from Schizosaccharomyces pombe, the mutant HPr (H15A) from Staphylococcus
      aureus, and a X-ray structure of human ubiquitin. In all three examples, the
      quality of the resulting final bundles was improved considerably by the use of
      additional substitute restraints, as assessed quantitatively by the calculation
      of RMSD values to the "true" structure and NMR R-factors directly calculated from
      the original NOESY spectra or the published diffraction data.

PMID- 19838809
TI  - Improved drought and salt stress tolerance in transgenic tobacco overexpressing a
      novel A20/AN1 zinc-finger "AlSAP" gene isolated from the halophyte grass
      Aeluropus littoralis.
AB  - We describe here the isolation of a novel gene, designated AlSAP, from A.
      littoralis in a first step to exploit the potential of this halophyte grass as a
      genetic resource to improve salt and drought tolerance in plants and,
      particularly, in cereals. The Aeluropus genome contains a single AlSAP gene which
      has an intron at its 5'UTR. Sequence homology analysis showed that the AlSAP
      protein is characterized by the presence of two conserved zinc-finger domains A20
      and AN1. AlSAP is induced not only by various abiotic stresses such as salt,
      osmotic, heat and cold but, also by abscisic acid (ABA) and salicylic acid (SA).
      Tobacco plants expressing the AlSAP gene under the control of the duplicated
      CaMV35S promoter exhibited an enhanced tolerance to abiotic stresses such as
      salinity (350 mM NaCl), drought (soil Relative Water Content (RWC) = 25%), heat
      (55 degrees C for 2.5 h) and freezing (-20 degrees C for 3 h). Moreover, under
      high salt and drought conditions, the transgenic plants were able to complete
      their life cycle and to produce viable seeds while the wild-type plants died at
      the vegetative stage. Measurements of the leaf RWC and of the root and leaf
      endogenous Na(+) and K(+) levels in AlSAP transgenic lines compared to wild-type
      tobacco, showed an evident lower water loss rate and a higher Na(+) accumulation
      in senescent-basal leaves, respectively. Finally, we found that the steady state
      levels of transcripts of eight stress-related genes were higher in AlSAP
      transgenic lines than in wild-type tobacco. Taken together, these results show
      that AlSAP is a potentially useful candidate gene for engineering drought and
      salt tolerance in cultivated plants.

PMID- 19838810
TI  - Conversion and degradation of shellfish wastes by Serratia sp. TKU016
      fermentation for the production of enzymes and bioactive materials.
AB  - A chitosanase and a protease were purified from the culture supernatant of
      Serratia sp. TKU016 with shrimp shell as the sole carbon/nitrogen source. The
      molecular masses of the chitosanase and protease determined by SDS-PAGE were
      approximately 65 and 53 kDa, respectively. The chitosanase was inhibited
      completely by Mn2+, but the protease was enhanced by all of tested divalent
      metals. The optimum pH, optimum temperature, pH stability, and thermal stability
      of the chitosanase and protease were (pH 7, 50 degrees C, pH 6-7, <50 degrees C)
      and (pH 8-10, 40 degrees C, pH 5-10, <50 degrees C), respectively. SDS (2 mM) had
      stimulatory effect on TKU016 protease activity. The result demonstrates that
      TKU016 protease is SDS-resistant protease and probably has a rigid structure.
      Besides, TKU016 culture supernatant (2% SPP) incubated for 2 days has the highest
      antioxidant activity, the DPPH scavenging ability was about 76%. With this
      method, we have shown that shrimp shell wastes can be utilized and it's effective
      in the production of enzymes, antioxidants, peptide and reducing sugar,
      facilitating its potential use in biological applications and functional foods.

PMID- 19838811
TI  - Rat forming incisor requires a rigorous ECM remodeling modulated by MMP/RECK
      balance.
AB  - Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) is a single
      membrane-anchored MMP-regulator and regulates matrix metalloproteinases (MMP) 2,
      9 and 14. In turn, MMPs are endopeptidases that play a pivotal role in remodeling
      ECM. In this work, we decided to evaluate expression pattern of RECK in growing
      rat incisor during, specifically focusing out amelogenesis process. Based on
      different kinds of ameloblasts, our results showed that RECK expression was
      conducted by secretory and post-secretory ameloblasts. At the secretory phase,
      RECK was localized in the infra-nuclear region of the ameloblast, outer
      epithelium, near blood vessels, and in the stellate reticulum. From the
      transition to the maturation phases, RECK was strongly expressed by non
      epithelial immuno-competent cells (macrophages and/or dendritic-like cells) in
      the papillary layer. From the transition to the maturation stage, RECK expression
      was increased. RECK mRNA was amplified by RT-PCR from whole enamel organ. Here,
      we verified the presence of RECK mRNA during all stages of amelogenesis. These
      events were governed by ameloblasts and by non-epithelial cells residents in the
      enamel organ. Concluding, we found differential expression of MMPs-2, -9 and RECK
      in the different phases of amelogenesis, suggesting that the tissue remodeling is
      rigorously controlled during dental mineralization.

PMID- 19838814
TI  - The testing effect on skills learning might last 6 months.
AB  - In a recent study we found that testing as a final activity in a skills course
      increases the learning outcome compared to spending an equal amount of time
      practicing. Whether this testing effect measured as skills performance can be
      demonstrated on long-term basis is not known. The research question was: does
      testing as a final activity in a cardio-pulmonary resuscitation (CPR) skills
      course increase learning outcome when assessed after half a year, compared to
      spending an equal amount of time practicing? The study was an assessor-blinded
      randomised controlled trial. A convenient sample of 7th semester medical students
      attending a mandatory CPR course was randomised to intervention course or control
      course. Participants were taught in small groups. The intervention course
      included 3.5 h skills training plus 30 min of skills testing. The practice-only
      control course lasted 4 h. Both groups were invited to a retention assessment of
      CPR skills half a year later. Participants included 89/180 (50%) of those invited
      to participate in the study. Mean performance score was 75.9 (SD 11.0) in the
      intervention group (N = 48) and 70.3 (SD 17.1) in the control group, effect size
      0.4. The difference between groups was not statistically significant, P = 0.06.
      This study suggests that testing as a final activity in a CPR skills course might
      have an effect on long-term learning outcome compared to spending an equal amount
      of time practicing the skills. Although this difference was not statistically
      significant, the identified effect size of 0.4 can have important clinical and
      educational implications.

PMID- 19838812
TI  - Atrophic gastritis and the risk of incident colorectal cancer.
AB  - Previous studies evaluating whether risk factors for gastric cancer are also
      associated with colorectal cancer (CRC) have shown inconsistent results. We
      prospectively examined the association of atrophic gastritis, a pre-malignant
      condition for gastric cancer and long-term sequelae common to many exposure
      factors, and the risk of incident CRC. METHODS: A total of 20,928 Finnish male
      smokers, aged 50-69, who were participants in the Alpha-Tocopherol, Beta-Carotene
      Cancer Prevention Study (ATBC) had serum pepsinogen I (SPGI) levels measured.
      Participants with low SPGI levels (< 25 microg/l; n = 1,665) were invited for
      gastroscopy. Of these, 1,059 (63.6%) participants underwent gastroscopy and
      atrophic gastritis was histologically confirmed in 1,006 (95.0%) participants. We
      used Cox proportional hazards regression to evaluate the risk of incident CRC.
      RESULTS: During a mean follow-up of 11.3 years (236,258 person-years), 425
      incident CRCs were diagnosed. The incidence rates were 1.82, 1.48, and 1.82 per
      1,000 person-years of follow-up for participants with normal SPGI (> or =25
      microg/l), low SPGI, and histologically confirmed atrophic gastritis,
      respectively. Compared to subjects with normal SPGI, there was no increased risk
      of CRC among subjects with low SPGI (Adjusted Hazard Ratio (HR) = 0.71; 95% CI:
      0.47-1.05) and among those with histologically confirmed atrophic gastritis
      (Adjusted HR = 0.86; 95% CI: 0.55-1.34). CONCLUSION: Atrophic gastritis is not
      associated with an increased risk of colorectal cancer among male smokers.

PMID- 19838815
TI  - Native granule associated short chain length polyhydroxyalkanoate synthase from a
      marine derived Bacillus sp. NQ-11/A2.
AB  - A rapidly growing marine derived Bacillus sp. strain NQ-11/A2, identified as
      Bacillus megaterium, accumulated 61% polyhydroxyalkanoate by weight. Diverse
      carbon sources served as substrates for the accumulation of short chain length
      polyhydroxyalkanoate. Three to nine granules either single or attached as buds
      could be isolated intact from each cell. Maximum activity of polyhydroxyalkanoate
      synthase was associated with the granules. Granule-bound polyhydroxyalkanoate
      synthase had a K(m) of 7.1 x 10(-5) M for DL-beta-hydroxybutyryl-CoA. Temperature
      and pH optima for maximum activity were 30 degrees C and 7.0, respectively.
      Sodium ions were required for granule-bound polyhydroxyalkanoate synthase
      activity and inhibited by potassium. Granule-bound polyhydroxyalkanoate synthase
      was apparently covalently bound to the polyhydroxyalkanoate-core of the granules
      and affected by the chaotropic reagent urea. Detergents inhibited the granule
      bound polyhydroxyalkanoate synthase drastically whilst glycerol and bovine serum
      albumin stabilized the synthase.

PMID- 19838816
TI  - Detection of prescription errors by a unit-based clinical pharmacist in a
      nephrology ward.
AB  - OBJECTIVE: To determine the impact of a clinical pharmacist on detection and
      prevention of prescription errors at the nephrology ward of a referral hospital.
      SETTING: Nephrology ward of a major referral hospital in Southern Iran. METHOD:
      During a 4-month period, a clinical pharmacist was assigned to review medication
      order sheets and drug orders three times a week at the nephrology ward. Besides
      chart review, the clinical pharmacist participated in medical rounds once a week.
      The occurrence of prescribing errors, and related harm was determined on
      hospitalized patients in this ward during the 4 month period. When an error was
      detected, intervention was made after agreement of the attending physician. MAIN
      OUTCOME MEASURES: Number and types of prescribing errors, level of harm, and
      number of interventions were determined. RESULTS: Seventy six patient charts were
      reviewed during the 4-month period. A total of 818 medications were ordered in
      these patients. Eighty six prescribing errors were detected in 46 hospital
      admissions. The mean age of the patients was 47.7 +/- 17.2. Fifty five percent
      were male while 45% were female. Different types of prescribing errors and their
      frequencies were as follows: wrong frequency (37.2%), wrong drug selection
      (19.8%), overdose (12.8%), failure to discontinue (10.5%), failure to order (7
      %), under- dose (3.5%), wrong time (3.5%), monitoring (3.5%), wrong route (1.2%),
      and drug interaction (1.2 %). The attending physician agreed to 96.5% of the
      prescription errors detected, and interventions were made. Although 89.5% of the
      detected errors caused no harm, 4(4.7%) of the errors increased the need for
      monitoring, 2 (2.3%) increased length of stay, and 2 (2.3%) led to permanent
      patient harm. CONCLUSION: presence of a clinical pharmacist at the nephrology
      ward helps in early detection of prescription errors, and therefore potential
      prevention of negative consequences due to drug administration.

PMID- 19838817
TI  - Isolation and antifungal susceptibility of Exophiala dermatitidis isolates from
      human stool samples in Nigeria.
AB  - We screened a total of 460 stool samples from humans with and without underlying
      disease for the black yeast and neurotrope, Exophiala dermatitidis using
      conventional and molecular identification procedures. Sixteen (3.5%) samples were
      positive. Twelve out of the sixteen positive samples where the fungus was
      recovered were from individuals who had diarrhoea at the moment of isolation. Two
      asymptomatic positive cases were within the age bracket of 21-30. Susceptibility
      testing of the strains using the CLSI M38 protocol suggests that almost all the
      strains were susceptible to amphotericin B, 5 fluorocytosine, itraconazole,
      fluconazole and voriconazole. Considering the health risk currently posed by this
      organism in Asia, especially among healthy younger subjects of the population and
      the scarcity of data on this fungus in Africa in general and Nigeria in
      particular, some recommendations were suggested.

PMID- 19838818
TI  - Identification and characterization of a novel variant of the human P2X(7)
      receptor resulting in gain of function.
AB  - The P2X(7) receptor exhibits significant allelic polymorphism in humans, with
      both loss and gain of function variants potentially impacting on a variety of
      infectious and inflammatory disorders. At least five loss-of-function
      polymorphisms (G150R, R307Q, T357S, E496A, and I568N) and two gain-of-function
      polymorphisms (H155Y and Q460R) have been identified and characterized to date.
      In this study, we used RT-PCR cloning to isolate and characterize P2X(7) cDNA
      clones from human PBMCs and THP-1 cells. A previously unreported variant with
      substitutions of V80M and A166G was identified. When expressed in HEK293 cells,
      this variant exhibited heightened sensitivity to the P2X(7) agonist (BzATP)
      relative to the most frequent allele, as shown by pore formation measured by
      fluorescent dye uptake into cells. Mutational analyses showed that A166G
      alteration was critical for the gain-of-function change, while V80M was not. Full
      length variants with multiple previously identified nonsynonymous SNPs (H155Y,
      H270R, A348T, and E496A) were also identified. Distinct functional phenotypes of
      the P2X(7) variants or mutants constructed with multiple polymorphisms were
      observed. Gain-of-function variations (A166G or H155Y) could not rescue the loss
      of-function E496A polymorphism. Synergistic effects of the gain-of-function
      variations were also observed. We also identified the A348T alteration as a weak
      gain-of-function variant. Thus, these results identify the new gain-of-function
      variant A166G and demonstrate that multiple-gene polymorphisms contribute to
      functional phenotypes of the human P2X(7) receptor. Furthermore, the results
      demonstrate that the C-terminal of the cysteine-rich domain 1 of P2X(7) is
      critical for regulation of P2X(7)-mediated pore formation.

PMID- 19838820
TI  - Microarray profile of brain aging-related genes in the frontal cortex of SAMP8.
AB  - This study examined the protein expression profile changes in the brain of
      senescence-accelerated mice/prone 8 (SAMP8) model. Two approaches, namely
      microarray and RT-PCR, were used in the study. Four genes, which are orthologous
      to human, were found to differentially express in the aging brain of mice. In
      this study, we examined the differentially expressed genes in the frontal cortex
      of the SAMP8 mice of two different ages (4 and 12 month old). Four orthologous
      genes (i.e., guanine nucleotide binding protein-alpha q polypeptide, kinesin
      family member 1B, sortilin 1, and somatostatin) showed significant changes in
      expression with aging. This study may provide important information on the
      mechanism of aging or aging-related diseases such as Alzheimer's diseases.

PMID- 19838821
TI  - Synaptic depression and aberrant excitatory network activity in Alzheimer's
      disease: two faces of the same coin?
AB  - Neurodegenerative diseases, including Alzheimer's disease (AD), target specific
      and functionally connected neuronal networks, raising the possibility that
      neurodegeneration may spread through abnormal patterns of neural network
      activity. AD is associated with high levels of amyloid-beta (A beta) peptides in
      the brain, synaptic depression, aberrant excitatory neuronal activity, and
      cognitive decline. However, the relationships among these alterations and their
      underlying mechanisms are poorly understood. In experimental models of AD, high
      concentrations of pathogenic A beta assemblies reduce glutamatergic transmission
      and enhance long-term depression at the synaptic level. At the network level,
      they cause dysrhythmias, including neuronal synchronization, epileptiform
      activity, seizures, and postictal suppression. Both synaptic depression and
      aberrant network synchronization likely interfere with activity-dependent
      synaptic regulation, which is critical for learning and memory. Abnormal patterns
      of neuronal activity across functionally connected brain regions may also trigger
      and perpetuate trans-synaptic mechanisms of neurodegeneration. It remains to be
      determined if synaptic depression and network dysrhythmias are mechanistically
      related, which of them is primary or secondary, and whether normalization of one
      will prevent the other as well as cognitive dysfunction in AD.

PMID- 19838819
TI  - The role of tenascin-C in tissue injury and tumorigenesis.
AB  - The extracellular matrix molecule tenascin-C is highly expressed during embryonic
      development, tissue repair and in pathological situations such as chronic
      inflammation and cancer. Tenascin-C interacts with several other extracellular
      matrix molecules and cell-surface receptors, thus affecting tissue architecture,
      tissue resilience and cell responses. Tenascin-C modulates cell migration,
      proliferation and cellular signaling through induction of pro-inflammatory
      cytokines and oncogenic signaling molecules amongst other mechanisms. Given the
      causal role of inflammation in cancer progression, common mechanisms might be
      controlled by tenascin-C during both events. Drugs targeting the expression or
      function of tenascin-C or the tenascin-C protein itself are currently being
      developed and some drugs have already reached advanced clinical trials. This
      generates hope that increased knowledge about tenascin-C will further improve
      management of diseases with high tenascin-C expression such as chronic
      inflammation, heart failure, artheriosclerosis and cancer.

PMID- 19838822
TI  - Cloning of circular DNAs from microorganisms using a novel plasmid capture
      system.
AB  - Plasmid capture system (PCS) facilitates cloning and manipulation of circular
      double-stranded DNA. We recently developed an improved PCS (PCS-LZ) to clone
      relatively large DNA molecules of 30-150 kb. The PCS-LZ donor consists of a mini
      F replicon and a kanamycin resistance marker between Tn7 left and Tn7 right ends.
      Both the replicon and marker gene of the PCS-LZ donor are transferred into target
      plasmid DNAs by in vitro transposition, followed by replication in E. coli.
      Colonies are tested for lacZ expression by blue/white screening. Circular DNAs
      were obtained from plasmids of Bacillus thuringiensis, genome segments of Cotesia
      glomerata bracovirus and polymorphic genomes of Autographa californica
      nucleopolyhedrovirus. PCS-LZ is a powerful tool for use in genomic analysis and
      mutagenesis in microorganisms including invertebrate pathogens.

PMID- 19838823
TI  - A patterned abrasion on the neck of an infant: inflicted injury or not?

PMID- 19838824
TI  - Infiltrating carcinoma of the breast mimicking electrocution.

PMID- 19838825
TI  - Long-term data archiving.

PMID- 19838826
TI  - Quantitative biomarker assay with microfluidic paper-based analytical devices.
AB  - This article describes the use of microfluidic paper-based analytical devices
      (muPADs) to perform quantitative chemical assays with internal standards.
      MicroPADs are well-suited for colorimetric biochemical assays; however, errors
      can be introduced from the background color of the paper due to batch difference
      and age, and from color measurement devices. To reduce errors from these sources,
      a series of standard analyte solutions and the sample solution are assayed on a
      single device with multiple detection zones simultaneously; an analyte
      concentration calibration curve can thus be established from the standards. Since
      the muPAD design allows the colorimetric measurements of the standards and the
      sample to be conducted simultaneously and under the same condition, errors from
      the above sources can be minimized. The analytical approach reported in this work
      shows that muPADs can perform quantitative chemical analysis at very low cost.

PMID- 19838827
TI  - Peak assignment in multi-capillary column-ion mobility spectrometry using
      comparative studies with gas chromatography-mass spectrometry for VOC analysis.
AB  - Over the past years, ion mobility spectrometry (IMS) as a well established method
      within the fields of military and security has gained more and more interest for
      biological and medical applications. This highly sensitive and rapid separation
      technique was crucially enhanced by a multi-capillary column (MCC), pre
      separation for complex samples. In order to unambiguously identify compounds in a
      complex sample, like breath, by IMS, a reference database is mandatory. To obtain
      a first set of reference data, 16 selected volatile organic substances were
      examined by MCC-IMS and comparatively analyzed by the standard technique for
      breath research, thermal desorption-gas chromatography-mass spectrometry.
      Experimentally determined MCC and GC retention times of these 16 compounds were
      aligned and their relation was expressed in a mathematical function. Using this
      function, a prognosis of the GC retention time can be given very precisely
      according to a recorded MCC retention time and vice versa. Thus, unknown MCC-IMS
      peaks from biological samples can be assigned-after alignment via the estimated
      GC retention time-to analytes identified by GC/MS from equivalent accomplished
      data. One example of applying the peak assignment strategy to a real breath
      sample is shown in detail.

PMID- 19838828
TI  - Optimization and validation of a liquid chromatography-tandem mass spectrometry
      method for the simultaneous quantification of nicotine, cotinine, trans-3'
      hydroxycotinine and norcotinine in human oral fluid.
AB  - An analytical procedure was developed and validated for the simultaneous
      identification and quantification of nicotine, cotinine, trans-3'
      hydroxycotinine, and norcotinine in 0.5 mL of human oral fluid collected with the
      Quantisal oral fluid collection device. Solid phase extraction and liquid
      chromatography-tandem mass spectrometry with multiple reaction monitoring were
      utilized. Endogenous and exogenous interferences were extensively evaluated.
      Limits of quantification were empirically identified by decreasing analyte
      concentrations. Linearity was from 1 to 2,000 ng/mL for nicotine and norcotinine,
      0.5 to 2,000 ng/mL for trans-3'-hydroxycotinine, and 0.2 to 2,000 ng/mL for
      cotinine. Correlation coefficients for calibration curves were >0.99 and analytes
      quantified within +/-13% of target at all calibrator concentrations. Suitable
      analytical recovery (>91%) was achieved with extraction efficiencies >56% and
      matrix effects <29%. This assay will be applied to the quantification of nicotine
      and metabolites in oral fluid in a clinical study determining the most
      appropriate nicotine biomarker concentrations differentiating active, passive,
      and environmental nicotine exposure.

PMID- 19838829
TI  - Postoperative spinal recurrence of craniopharyngioma.
AB  - PURPOSE: Remote recurrence of craniopharyngioma is an unusual postoperative
      complication. It occurs either along a previous surgical route or by seeding via
      cerebrospinal fluid (CSF). METHODS: A 49-year-old male had been operated on twice
      for a suprasellar craniopharyngioma in September 1999 and February 2003. From
      August 2003, he noted progressive low-back pain followed by ischialgia along the
      right S1 dermatome, which was symptomatic of an intradural tumor at the level of
      the first sacral segment. RESULTS: Total resection was performed and the tumor
      was histologically confirmed to be an adamantinomatous craniopharyngioma.
      CONCLUSIONS: We report the first case of remote spinal recurrence of
      adamantinomatous craniopharyngioma. No growth hormone therapy was administered to
      this patient. One must bear in mind this rare complication in craniopharyngioma
      patients and underline the importance of long-term follow-up.

PMID- 19838830
TI  - Back pain amongst 8,910 young Australian women: a longitudinal analysis of the
      use of conventional providers, complementary and alternative medicine (CAM)
      practitioners and self-prescribed CAM.
AB  - Back problems and back pain are amongst the most prevalent conditions afflicting
      Australians and carry high direct and indirect costs for the health care systems
      of all developed countries. A major gap in the research literature on this topic
      is the longitudinal analysis of health seeking behaviour for people with back
      pain. All studies to date have been cross-sectional and it is important that the
      use of different providers (both conventional and complementary and alternative
      medicine, CAM) is examined over time. This study analysed data from a
      longitudinal study conducted over a 3-year period on 8,910 young Australian
      women. Information on health service use, self-prescribed treatments, and health
      status was obtained from two questionnaires mailed to study participants in 2003
      and 2006. We found that there is little difference in the consultation practises
      or use of self-prescribed CAM between women who recently sought help for back
      pain and women who had longer-term back pain; the only difference being that
      women with longer-term back pain consulted more with chiropractors. We conclude
      that women who seek help for their back pain are frequent visitors to a range of
      conventional and CAM practitioners and are also high users of self-prescribed CAM
      treatments. The frequent use of a range of conventional providers and
      practitioner-based and self-prescribed CAM amongst women with back pain warrants
      further investigation.

PMID- 19838831
TI  - Gastric gastrointestinal stromal tumor (GIST) incidentally found and resected
      during laparoscopic sleeve gastrectomy.
AB  - The incidence of incidental pathology found during laparoscopic bariatric surgery
      has been estimated to be around 2%, and gastric gastrointestinal stromal tumors
      (GISTs) have been found in 0.8% of patients, constituting a rather uncommon
      finding. Safe laparoscopic resection of gastric GISTs is an established procedure
      and has been described associated to gastric Roux-en-Y bypass for morbid obesity.
      We discuss one case of a gastric GIST incidentally discovered during laparoscopic
      sleeve gastrectomy for morbid obesity. The procedure was performed via
      laparoscopy, and the patient recovered without any complication. Currently, the
      patient has lost weight according to what was expected, is asymptomatic, and free
      of disease.

PMID- 19838832
TI  - Polymorphisms in the HSP90AA1 5' flanking region are associated with scrapie
      incubation period in sheep.
AB  - Susceptibility to scrapie is mainly controlled by point mutations at the PRNP
      locus. However, additional quantitative trait loci (QTL) have been identified
      across the genome including a region in OAR18. The gene which encodes the
      inducible form of the cytoplasmic Hsp90 chaperone (HSP90AA1) maps within this
      region and seems to be associated with the resistance/susceptibility to scrapie
      in sheep. Here, we have analyzed several polymorphisms which were previously
      described in the ovine HSP90AA1 5' flanking region and in intron 10 in two
      naturally scrapie infected Romanov sheep populations. First, we have studied 58
      ARQ/VRQ animals pertaining to the sire family where the QTL influencing scrapie
      incubation period in OAR18 was detected. We have found a significant association
      between polymorphisms localized at -660 and -528 in the HSP90AA1 5' flanking
      region and the scrapie incubation period. These two polymorphisms have also been
      studied in a second sample constituted by 62 VRQ/VRQ sheep showing an extreme
      incubation period. Results are concordant with the first dataset. Finally, we
      have studied the HSP90AA1 expression in scrapie and control animals (N = 41) with
      different HSP90AA1 genotypes by real time PCR on blood samples. The HSP90AA1
      expression rate was equivalent in CC(-600)AA(-528) and CG(-600)AG(-528) scrapie
      resistant animals (ARR/ARR) and was higher in their CC(-600)AA(-528) than in
      their CG(-600)AG(-528) scrapie susceptible counterparts (VRQ/VRQ). Our results
      support the hypothesis that the ovine HSP90AA1 gene acts as a modulator of
      scrapie susceptibility, contributing to the observed differences in the
      incubation period of scrapie infected animals with the same PRNP genotype.

PMID- 19838834
TI  - Acute posterior multifocal placoid pigment epitheliopathy with concurrent
      cerebral vasculitis and sarcoidosis.

PMID- 19838833
TI  - Proteasome inhibition induces hsp30 and hsp70 gene expression as well as the
      acquisition of thermotolerance in Xenopus laevis A6 cells.
AB  - Previous studies have shown that inhibiting the activity of the proteasome leads
      to the accumulation of damaged or unfolded proteins within the cell. In this
      study, we report that proteasome inhibitors, lactacystin and carbobenzoxy-L
      leucyl-L-leucyl-L-leucinal (MG132), induced the accumulation of ubiquitinated
      proteins as well as a dose- and time-dependent increase in the relative levels of
      heat shock protein (HSP)30 and HSP70 and their respective mRNAs in Xenopus laevis
      A6 kidney epithelial cells. In A6 cells recovering from MG132 exposure, HSP30 and
      HSP70 levels were still elevated after 24 h but decreased substantially after 48
      h. The activation of heat shock factor 1 (HSF1) may be involved in MG132-induced
      hsp gene expression in A6 cells since KNK437, a HSF1 inhibitor, repressed the
      accumulation of HSP30 and HSP70. Exposing A6 cells to simultaneous MG132 and mild
      heat shock enhanced the accumulation of HSP30 and HSP70 to a much greater extent
      than with each stressor alone. Immunocytochemical studies determined that HSP30
      was localized primarily in the cytoplasm of lactacystin- or MG132-treated cells.
      In some cells treated with higher concentrations of MG132 or lactacystin, we
      observed in the cortical cytoplasm (1) relatively large HSP30 staining
      structures, (2) colocalization of actin and HSP30, and (3) cytoplasmic areas that
      were devoid of HSP30. Lastly, MG132 treatment of A6 cells conferred a state of
      thermotolerance such that they were able to survive a subsequent thermal
      challenge.

PMID- 19838835
TI  - Cancer survivorship care for the general internist: have we paved the way for a
      smoother transition?

PMID- 19838836
TI  - The expanding use of third-generation aromatase inhibitors: what the general
      internist needs to know.
AB  - BACKGROUND: Breast cancer patients represent the largest group of adult cancer
      survivors in the US. Most breast cancers in women 50 years of age and older are
      hormone receptor positive. Third generation aromatase inhibitors (AIs) are the
      newest class of drugs used in treating hormone responsive breast cancer. It is
      often during start of adjuvant hormone therapy that the breast cancer patient
      establishes (or reestablishes) close follow-up with their general internist.
      OBJECTIVE: Given the large numbers of breast cancer patients in the US and the
      increasing use of third generation AI's, general internists will need to have a
      clear understanding of these drugs including their benefits and potential harms.
      Currently there are three third generation aromatase inhibitors FDA approved for
      use in the US. All have been shown to be superior to tamoxifen in disease free
      survival (DFS) in the treatment of both metastatic and early breast cancers.
      RESULTS: While the data on side effects is limited, AI (compared to tamoxifen)
      may result in higher rates of osteoporosis and fractures, more arthralgias, and
      increased vaginal dryness and dysparuenia. Limited information on their effects
      on the cardiovascular system and neuro-cognitive function are also available.
      Patient's receiving adjuvant hormone therapy are generally considered disease
      free or disease stable and require less intensive monitoring by their breast
      cancer specialist. CONCLUSIONS: In situations where patients experience
      significant negative side effects from AI therapy, discussions to discontinue
      treatment (and switch to an alternative endocrine therapy) should involve the
      cancer specialist and take into consideration the patient's risk for breast
      cancer recurrence and the impact of therapy on their quality of life. In some
      cases, patients may choose to never initiate AI treatment. In other cases,
      patients may choose to prematurely discontinue therapy even if therapy is well
      tolerated. In both settings increased knowledge by the general internists will
      likely facilitate discussions of risks versus benefits of therapy and possibly
      improve compliance to adjuvant hormone therapy.

PMID- 19838837
TI  - Prostate cancer survivorship: prevention and treatment of the adverse effects of
      androgen deprivation therapy.
AB  - BACKGROUND: More than one-third of the estimated 2 million prostate cancer
      survivors in the United States receive androgen deprivation therapy (ADT). This
      population of mostly older men is medically vulnerable to a variety of treatment
      associated adverse effects. MEASUREMENTS AND RESULTS: Androgen-deprivation
      therapy (ADT) causes loss of libido, vasomotor flushing, anemia, and fatigue.
      More recently, ADT has been shown to accelerate bone loss, increase fat mass,
      increase cholesterol and triglycerides, and decrease insulin sensitivity.
      Consistent with these adverse metabolic effects, ADT has also recently been
      associated with greater risks for fractures, diabetes and cardiovascular disease.
      CONCLUSION: Primary care clinicians and patients should be aware of the potential
      benefits and harms of ADT. Screening and intervention to prevent treatment
      related morbidity should be incorporated into the routine care of prostate cancer
      survivors. Evidence-based guidelines to prevent fractures, diabetes, and
      cardiovascular disease in prostate cancer survivors represent an important unmet
      need. We recommend the adapted use of established practice guidelines designed
      for the general population.

PMID- 19838838
TI  - Chronic health conditions in childhood cancer survivors: is it all treatment
      related--or do genetics play a role?
AB  - BACKGROUND: High-intensity, risk-based therapeutic strategies for childhood
      cancer have resulted in long-term survival rates that now approach 80%. However,
      the growing population of survivors is at a substantial risk for treatment
      related complications that can significantly impact quantity and quality of
      survival. It is increasingly recognized that many of these complications result
      from complex interactions between therapeutic exposures and genetic
      susceptibility. OBJECTIVE: This review is designed to increase general clinician
      awareness of the ongoing efforts by investigators to understand the interactions
      between therapeutic exposures and genetic susceptibility to therapy-related
      complications. RESULTS: Most studies have relied on a biologically plausible
      candidate gene approach to evaluate genetic susceptibility. This has resulted in
      the identification of unique genetic polymorphisms that could alter metabolic
      pathways of therapeutic agents associated with specific adverse events. We
      highlight some of these findings and discuss their implications for future
      prevention strategies, as well as their role in elucidating the pathophysiology
      of these complex diseases. CONCLUSION: Research exploring the role of genetic
      susceptibility in the development of therapy-related adverse outcomes is still in
      its infancy. There is a need for continued efforts to study these outcomes in the
      context of complex gene-gene and gene-environment interactions unique to cancer
      survivors. A better understanding of the pathogenesis of these outcomes will help
      develop effective targeted prevention strategies.

PMID- 19838839
TI  - Contraception for cancer survivors.
AB  - Women who have survived cancer may need guidance in choosing a method of
      contraception. This paper reviews the evidence supporting the safety and efficacy
      of available methods of contraception for cancer survivors and concludes that the
      Copper T380A intrauterine device (IUD), a highly effective, reversible, long
      acting, hormone-free method should be considered a first-line contraceptive
      option for women with a history of a hormonally mediated cancer. However, the
      levonorgestrel-containing IUD may be preferable for women being treated with
      tamoxifen and women who have survived non-hormonally mediated cancers. Women with
      IUDs can undergo all forms of imaging, including computed tomography and magnetic
      resonance imaging.

PMID- 19838840
TI  - General internist communication about sexual function with cancer survivors.
AB  - BACKGROUND: Sexual dysfunction is an important issue that affects many cancer
      survivors who are increasingly being cared for by internists. OBJECTIVE: To
      examine the attitudes and reported practices of internists regarding survivorship
      care as it pertains to sexual dysfunction. DESIGN: Surveys were sent to 406
      physicians affiliated with the Department of Internal Medicine at the University
      of Colorado Denver School of Medicine. Of the 319 eligibles, 227 were returned
      (71% RR). MAIN RESULTS: Of the 227 responders, 46% were "somewhat/very" likely to
      initiate a conversation about sexual dysfunction; 62% "never/rarely" addressed
      sexual dysfunction. Each additional weekly hour spent in patient care was
      associated with a 2% increase in the likelihood of sexual dysfunction being
      addressed or discussions about sexual dysfunction being initiated. Reported
      inadequate preparation/formal training around survivorship issues was associated
      with sexual dysfunction being addressed less often (odds ratio [OR] = 0.45).
      Perception of patient anxiety or fears about health was associated with sexual
      dysfunction being addressed more often (OR = 2.38). Perceived preparedness to
      evaluate long-term effects was associated with a greater likelihood of physicians
      initiating discussions about sexual functioning (OR = 2.49). CONCLUSIONS: Cancer
      survivors receive their long-term care from internists. Our results suggest that
      sexual dysfunction is often not addressed during their follow-up care. Additional
      training is needed to prepare physicians to negotiate this difficult issue.

PMID- 19838841
TI  - Cancer-related fatigue: the approach and treatment.
AB  - As the volume of cancer survivors continues to increase, clinicians are being
      faced with a growing number of patients with cancer-related fatigue (CRF).
      Survivors with a variety of malignancies may experience fatigue. Many potential
      barriers to the identification of this symptom in a cancer survivor may exist,
      due in part to both the patient and the clinician. Assessment of patients for
      fatigue is important because it can profoundly effect their daily lives. Many
      factors contribute to CRF. Hence, the clinician may face a daunting challenge in
      attempting to alleviate CRF. Treatment modalities for CRF include
      nonpharmacologic interventions, such as psychosocial interventions, exercise,
      sleep therapy, and acupuncture. Pharmacologic interventions include stimulants,
      namely modafinil and methylphenidate. In some patients antidepressants may be
      beneficial. Clinicians should assess cancer survivors for the presence of fatigue
      and focus on its treatment in an attempt to ensure that these patients have the
      best possible symptom control.

PMID- 19838842
TI  - Improving primary care for older adults with cancer and depression.
AB  - BACKGROUND: Depression is common among older cancer patients, but little is known
      about the optimal approach to caring for this population. This analysis evaluates
      the effectiveness of the Improving Mood-Promoting Access to Collaborative
      Treatment (IMPACT) program, a stepped care management program for depression in
      primary care patients who had an ICD-9 cancer diagnosis. METHODS: Two hundred
      fifteen cancer patients were identified from the 1,801 participants in the parent
      study. Subjects were 60 years or older with major depression (18%), dysthymic
      disorder (33%), or both (49%), recruited from 18 primary care clinics belonging
      to 8 health-care organizations in 5 states. Patients were randomly assigned to
      the IMPACT intervention (n = 112) or usual care (n = 103). Intervention patients
      had access for up to 12 months to a depression care manager who was supervised by
      a psychiatrist and a primary care provider and who offered education, care
      management, support of antidepressant management, and brief, structured
      psychosocial interventions including behavioral activation and problem-solving
      treatment. RESULTS: At 6 and 12 months, 55% and 39% of intervention patients had
      a 50% or greater reduction in depressive symptoms (SCL-20) from baseline compared
      to 34% and 20% of usual care participants (P = 0.003 and P = 0.029). Intervention
      patients also experienced greater remission rates (P = 0.031), more depression
      free days (P < 0.001), less functional impairment (P = 0.011), and greater
      quality of life (P = 0.039) at 12 months than usual care participants.
      CONCLUSIONS: The IMPACT collaborative care program appears to be feasible and
      effective for depression among older cancer patients in diverse primary care
      settings.

PMID- 19838844
TI  - The space in between.

PMID- 19838843
TI  - Cancer from both sides now: combining personal and research perspectives on
      survivorship.
AB  - Cancer survivorship is increasingly a situation of chronic disease management
      that needs to be integrated with the context of broader health and well-being.
      This perspective paper combines personal experiences and a professional research
      program to address the complexities of long-term management of cancer and
      integrated care and the importance of psychological distress and psychological
      growth expressed in diverse pathways of survivorship. The role of age is
      addressed as partially defining the extent and nature of long-term psychological
      effects. General internists are in a unique position to play a central role in
      enabling cancer survivors to integrate the cancer experience into their lives and
      their overall health and well-being.

PMID- 19838846
TI  - Seeking the proper tense.

PMID- 19838845
TI  - Self-identity after cancer: "survivor", "victim", "patient", and "person with
      cancer".
AB  - BACKGROUND: Living through cancer often involves developing new identities which
      may strongly influence well-being and relationships with care providers, yet
      little is currently known about these post-cancer identities. OBJECTIVES: To
      examine (1) the extent to which four post-cancer identities (patient, person who
      has had cancer, victim, and survivor) are adopted, (2) relations between each
      identity and involvement in cancer-related activities and mental and physical
      well-being, and (3) correlates of these identities. DESIGN: Cross-sectional
      questionnaire-based study. PARTICIPANTS: 168 young to middle-aged adults who had
      previously experienced cancer. MEASUREMENTS: Cancer identifications, background
      variables, psychological functioning, cancer risk appraisals and coping, cancer
      related activities, and mental and physical well-being. RESULTS: At least
      somewhat, 83% endorsed survivor identity, 81% identity of "person who has had
      cancer", 58% "patient", and 18% "victim". Identities were minimally correlated
      with one another and differentially associated with involvement in cancer-related
      activities. Survivor and person who has had cancer identities correlated with
      involvement in most cancer-related activities such as wearing cancer-related
      items and talking about prevention (ps < 0.5). Survivor identity correlated with
      better psychological well-being and post-traumatic growth, victim identity with
      poorer well-being (ps < 0.5); neither identifying as a patient nor a person with
      cancer was related to well-being. Through regression analyses, identities were
      shown to be explained by unique combination of background, functioning, appraisal
      and coping variables. CONCLUSIONS: Survivor identity appears most common and most
      associated with active involvement and better psychological well-being, but other
      identifications are also common and simultaneously held. Adoption of specific
      cancer identities is likely to impact interactions with health care providers,
      including those in general internal medicine, and health behavior changes.

PMID- 19838847
TI  - Financial status, employment, and insurance among older cancer survivors.
AB  - BACKGROUND: Few data are available about the socioeconomic impact of cancer for
      long-term cancer survivors. OBJECTIVES: To investigate socioeconomic outcomes
      among older cancer survivors compared to non-cancer patients. DATA SOURCE: 2002
      Health and Retirement Study. STUDY DESIGN: We studied 964 cancer survivors of > 4
      years and 14,333 control patients who had never had cancer from a population
      based sample of Americans ages >or= 55 years responding to the 2002 Health and
      Retirement Study. MEASURES: We compared household income, housing assets, net
      worth, insurance, employment, and future work expectations. ANALYSES: Propensity
      score methods were used to control for baseline differences between cancer
      survivors and controls. RESULTS: Female cancer survivors did not differ from non
      cancer patients in terms of income, housing assets, net worth, or likelihood of
      current employment (all P > 0.20); but more were self-employed (25.0% vs. 17.7%;
      P = 0.03), and fewer were confident that if they lost their job they would find
      an equally good job in the next few months (38.4% vs. 45.9%; P = 0.03). Among
      men, cancer survivors and noncancer patients had similar income and housing
      assets (both P >or= 0.10) but differed somewhat in net worth (P = 0.04). Male
      cancer survivors were less likely than other men to be currently employed (25.2%
      vs. 29.7%) and more likely to be retired (66.9% vs. 62.2%), although the P value
      did not reach statistical significance (P = 0.06). Men were also less optimistic
      about finding an equally good job in the next few months if they lost their
      current job (33.5% vs. 46.9%), although this result was not significant (P =
      0.11). CONCLUSIONS: Despite generally similar socioeconomic outcomes for cancer
      survivors and noncancer patients ages >or=55 years, a better understanding of
      employment experience and pessimism regarding work prospects may help to shape
      policies to benefit cancer survivors.

PMID- 19838848
TI  - The economic consequences of breast cancer adjuvant hormonal treatments.
AB  - RATIONALE: Adjuvant hormone therapy (HT) based on tamoxifen (TX) or aromatase
      inhibitors (AIs) has become the standard of care for treating hormone receptor 
      positive (HR+) breast cancer (BC) over the past 20 years. Based on clinical trial
      results, AI use is recommended by the American Society of Clinical Oncology for
      treatment of postmenopausal women with HR+ breast cancer. AIs, however, are
      significantly more expensive than TX, raising concerns about access and use of
      effective treatment among women of lower socio-economic status. OBJECTIVES: To
      examine the relationship between adjuvant HT modality and experience of financial
      hardship among a cohort of older BC survivors. Also, to examine the extent to
      which financial concerns affect the probability of switching between adjuvant HT
      modalities. DESIGN: Population-based, prospective survey study. PARTICIPANTS:
      Elderly (65+) women who had an incident BC surgery in 2003 and who reported
      receiving adjuvant HT during the first 12 months post-surgery. METHODS:
      Multivariate regression models. RESULTS: Use of AIs was associated with a
      significantly higher probability of financial hardship. Women who had taken only
      an AI were more likely to experience financial difficulty than women who took
      only TX (OR = 1.4; 95% CI: 1.1-1.7), but women who switched between TX and AI
      were not more likely to experience financial difficulty. Breast cancer survivors
      with no drug coverage (OR = 4.5; 95% CI: 3.3-5.9) or partial drug coverage (OR =
      3.6; 95% CI: 2.8-4.5) were more likely to experience financial difficulty
      compared to those with full coverage. Lack of drug coverage was also the main
      factor associated with the likelihood that BC survivors did not switch adjuvant
      HT modalities. CONCLUSIONS: Adjuvant HTs have important economic consequences for
      BC survivors. These consequences are ameliorated by full, but not partial, drug
      coverage.

PMID- 19838849
TI  - Establishing a general medical outpatient clinic for cancer survivors in a public
      city hospital setting.
AB  - INTRODUCTION: Many cancer centers and community hospitals are developing novel
      models of survivorship care. However, few are specifically focused on services
      for socio-economically disadvantaged cancer survivors. AIMS: To describe a new
      model of survivorship care serving culturally diverse, urban adult cancer
      patients and to present findings from a feasibility evaluation. SETTING: Adult
      cancer patients treated at a public city hospital cancer center. PROGRAM
      DESCRIPTION: The clinic provides comprehensive medical and psychosocial services
      for patients within a public hospital cancer center where they receive their
      oncology care. PROGRAM EVALUATION: Longitudinal data collected over a 3-year
      period were used to describe patient demographics, patient needs, and services
      delivered. Since inception, 410 cancer patients have been served. Demand for
      services has grown steadily. Hypertension was the most frequent comorbid
      condition treated. Pain, depression, cardiovascular disease, hyperlipidemia, and
      bowel dysfunction were the most common post-treatment problems experienced by the
      patients. Financial counseling was an important patient resource. DISCUSSION:
      This new clinical service has been well-integrated into its public urban hospital
      setting and constitutes an innovative model of health-care delivery for socio
      economically challenged, culturally diverse adult cancer survivors.

PMID- 19838850
TI  - Cancer survivorship: a new challenge for surgical and medical oncologists.
AB  - Increasingly, oncology practitioners are realizing that despite the "success" of
      cancer therapies, cancer survivors are facing previously unrecognized issues
      related to survivorship, including physical and psychosocial side-effects of the
      cancer and its treatment, second cancers, and practical and economic issues
      related to adjusting to life after their cancer diagnosis. In gastrointestinal
      cancers, traditionally, the medical and surgical oncologists charged with the
      care of the patient are not well-equipped to deal with these survivorship issues.
      At the Penn State Cancer Institute's newly formed Gastrointestinal Cancer
      Survivorship Clinic, we provide a full array of services to optimize care through
      a multi-disciplinary approach. By utilizing a multi-disciplinary model with the
      primary medical and surgical oncologists spearheading the survivorship initiative
      and psychological and pastoral support as a priority, we hope to optimize cancer
      survivor care and patient quality of life.

PMID- 19838851
TI  - Transitioning to breast cancer survivorship: perspectives of patients, cancer
      specialists, and primary care providers.
AB  - BACKGROUND: Limited research exists regarding views of patients, oncology
      specialists, and primary care providers (PCPs) concerning breast cancer
      survivorship care. OBJECTIVE: To qualitatively explore the needs and priorities
      of breast cancer survivors, oncology specialists, and PCPs. METHODS: Focus groups
      were conducted of survivors (21 in 5 groups), PCPs (15 in 2 groups), and oncology
      specialists (16 in 2 groups). One survivor group consisted of four African
      Americans. Discussions used a semi-structured guide, were transcribed verbatim,
      and were analyzed qualitatively. Groups explored transitions to follow-up,
      communication, patient needs, and provider roles. RESULTS: Survivors form intense
      relationships with specialists for reassurance and expertise. Many believed PCPs
      lacked necessary oncology expertise. Survivors reported psychosocial and
      communication issues. African-Americans cited concerns about access to care and
      clinical trials, as well as taboos to discussing cancer. Specialists reported
      that they struggle with discharging survivors due to protective relationships.
      PCPs were concerned about time and training to provide survivorship care and
      communication problems with oncologists. Written survivorship care plans were
      regarded by all groups as possibly helpful, but insufficient to ease the
      transition. CONCLUSIONS: Breast cancer patients may experience difficulties
      transitioning to survivorship, including ongoing psychosocial issues. African
      American patients may face additional and unique barriers to successful
      survivorship. Oncology specialists may have concerns about discharging cherished
      patients. These findings suggest a psychological component that may influence the
      use of written survivorship care plans. PCPs may need additional training and
      greater access to specialists in order to care for survivors.

PMID- 19838852
TI  - The potential of survivorship care plans in primary care follow-up of minority
      breast cancer patients.
AB  - BACKGROUND: When the clinical care of minority breast cancer survivors is
      transferred from oncology settings to primary care, quality of care may be
      compromised if their primary care providers do not have adequate cancer treatment
      records and follow-up care guidelines. Survivorship care plans (SCPs) given to
      survivors before they transition to primary care settings are designed to improve
      the transfer of this information. This study examined these issues in a sample of
      minority breast cancer survivors. DESIGN: During four focus groups with minority
      breast cancer survivors, data were collected about the types of information
      survivors remember receiving from their oncologists about follow-up health care
      needs. Survivors were also asked their opinions on the value and content of a
      survivorship care plan. RESULTS: Minority breast cancer survivors received
      variable amounts of information about their cancer treatments. They were
      dissatisfied with the amount of information they received on cancer-related side
      effects, including race-specific information. The American Society of Clinical
      Oncology's breast cancer survivorship care plan was viewed as important, but too
      highly technical and limited in information on side-effects and self-care
      approaches. CONCLUSIONS: Survivorship care plans may help increase information
      transfer from oncologists to patients and primary care providers, but the content
      of care plans needs to be adapted to minority patients' concerns. Primary care
      physicians may be challenged by survivors to explain recommended surveillance
      guidelines and to respond to untreated physical and psychosocial problems.

PMID- 19838853
TI  - Follow-up care delivery among colorectal cancer survivors most often seen by
      primary and subspecialty care physicians.
AB  - BACKGROUND: The Institute of Medicine has identified patients as a key source of
      information for assessing the quality of care. OBJECTIVE: To evaluate the
      association of physician specialty with the content and quality of follow-up
      cancer care. DESIGN AND PARTICIPANTS: Three hundred three colorectal cancer (CRC)
      survivors in Northern California were surveyed 2-5 years post-diagnosis.
      MEASUREMENTS: Specialty of physician seen most often [primary care physician
      (PCP), oncologist, surgeon, or gastroenterologist]; other physician specialties
      seen; patient characteristics; content of visits; patient-centered quality of
      follow-up care (communication, coordination, nursing, and staff interactions).
      MAIN RESULTS: A minority (16%) of CRC survivors reported that the doctor they
      most often saw for follow-up cancer care was a PCP, while 60% saw an oncologist.
      Many CRC survivors (40%) saw >1 physician for follow-up cancer care. Survivors
      most often seen by PCPs were more likely to have three or more medical
      comorbidities (70% vs. 51%, p = 0.012) than survivors seen by subspecialty
      physicians. Survivors seen by PCPs were less likely to report seeing a doctor for
      medical tests and more likely to report discussing disease prevention (82% vs.
      64%, p = 0.012) or diet (70% vs. 48%, p = 0.005) with their doctor. There were no
      significant specialty differences in patient-centered quality of follow-up cancer
      care. CONCLUSIONS: Cancer survivors' assessment of the quality of care was
      similar across specialties, while the content of follow-up cancer care varied by
      physician specialty. These findings provide important information about the
      potential value of primary care and the need for coordination when delivering
      care to CRC survivors.

PMID- 19838854
TI  - Receipt of provider advice for smoking cessation and use of smoking cessation
      treatments among cancer survivors.
AB  - BACKGROUND: As the number of cancer survivors increases, the assessment and
      intervention for smoking among survivors are increasingly important. OBJECTIVE:
      This study examined the extent to which cancer survivors reported being asked and
      advised about smoking by health-care providers and their use of smoking cessation
      treatments during quit attempts. DESIGN: The data were drawn from the 2005
      National Health Interview Survey, an annual health survey of US adults.
      PARTICIPANTS: The participants were 1,825 individuals who reported being
      diagnosed with cancer at least 1 year previously and provided data regarding
      their current smoking status. MEASUREMENTS: Participants completed items
      assessing demographics, health and health-care factors, and smoking-related
      variables. MAIN RESULTS: More than three-quarters of participants (81.0%)
      reported that their smoking status was known by a health-care provider. Among
      current smokers (17.6%) who visited a health-care provider in the past year,
      72.2% reported being advised to quit smoking by a provider. Factors associated
      with a higher rate of receiving advice to quit included greater cigarette
      consumption (P=0.008), more medical comorbidities (P= 0.001), high psychological
      distress (P= 0.003), and lack of health-care insurance (P = 0.03). Among current
      smokers who tried to quit in the last year, 33.5% used pharmacotherapy cessation
      treatment and 3.8% used an evidence-based behavioral treatment. CONCLUSIONS: This
      study reveals considerable missed opportunities for health-care providers to
      advise cancer survivors about smoking and provide evidence-based interventions.
      Systematic efforts are needed to increase the provision of smoking cessation
      advice and use of cessation treatments among cancer survivors.

PMID- 19838855
TI  - Breast, colorectal and prostate cancer screening for cancer survivors and non
      cancer patients in community practices.
AB  - BACKGROUND: Cancer survivors have cancer surveillance and preventive screening
      needs that require monitoring. Little is known regarding their patterns of care
      in community primary care practices. METHODS: Secondary analysis of 750 baseline
      patient surveys and medical record audits for patients ages 50+ years in 25
      community-based primary care practices (N = 109 survivors and 641 noncancer
      patients). RESULTS: Patient self-reported screening rates for breast cancer
      (72%), colorectal cancer (81%) and prostate cancer (77%) were higher for cancer
      survivors compared to noncancer patients (69%, 67%, 53%, respectively). Screening
      rates documented in the primary care records were lower for all cancers. Cancer
      survivors were more likely than others to report having been screened for
      colorectal cancer (P = 0.002) even after excluding colorectal cancer survivors
      from the analysis (P = 0.034). Male cancer survivors were more likely to report
      being screened for prostate cancer than those without cancer (P < 0.001), even
      after excluding prostate cancer survivors (P = 0.020). There were no significant
      differences in either self-reported or medical record report of breast cancer
      screening rates among cancer survivors and noncancer patients. CONCLUSIONS:
      Cancer survivors were more likely to self-report receipt of cancer screening than
      noncancer patients. Medical record reports of cancer screening were lower than
      self-reports for cancer survivors and noncancer patients. Identifying factors
      that affect cancer screening among cancer survivors is important and has
      implications for intervention design.

PMID- 19838856
TI  - A framework for developing, implementing, and evaluating a cancer survivorship
      curriculum for medical students.
AB  - BACKGROUND: Cancer survivorship care is not adequately addressed in current
      medical school curricula. OBJECTIVES: To develop, implement, and evaluate a
      modular cancer survivorship curriculum that is portable to other educational
      settings and is designed to provide medical students with a foundation of
      knowledge, attitudes, and skills related to care for cancer survivors. PROGRAM
      DESCRIPTION: An expert consensus panel developed a set of learning objectives
      related to cancer survivorship to guide the development of educational modules,
      such as computer-based self-instructional modules, problem-based learning cases,
      videos, and clinical exercises. Course and clerkship chairs were directly
      involved in the development and implementation of the modules. EVALUATION: A
      cohort study with a historical control group demonstrated that fourth-year
      medical students increased their knowledge in survivorship issues and their self
      reported level of comfort in care activities compared to similar students who did
      not receive the survivorship curriculum. CONCLUSIONS: Our framework resulted in a
      cancer survivorship curriculum that was implemented in a modular manner across
      the medical curriculum that improved learning and that is potentially portable to
      other educational settings.

PMID- 19838857
TI  - Cancer survivorship care: exploring the role of the general internist.
AB  - According to the National Cancer Institute (NCI), cancer survivorship encompasses
      the "physical, psychosocial, and economic issues of cancer from diagnosis until
      the end of life." Today, one in 30 Americans are cancer survivors. Almost two
      thirds have at least one chronic health condition. As the numbers of cancer
      survivors increase, cancer itself can be viewed as a chronic medical condition.
      This paper illustrates some of the challenges faced by cancer survivors. We
      discuss the limitations of current models of survivorship care, including shared
      care. In addition, we explore how the American Board of Internal Medicine's
      previously proposed credential of Comprehensive Care Internist could serve to
      define and integrate the complex needs of adult cancer survivors with the skills
      and talents of general internists.

PMID- 19838858
TI  - Keeping up with survivors: education across the spectrum of cancer.

PMID- 19838859
TI  - Cancer survivorship across the healthcare continuum.

PMID- 19838860
TI  - Gene cloning, expression, and characterization of a thermostable xylanase from
      Nesterenkonia xinjiangensis CCTCC AA001025.
AB  - An endo-beta-1,4-xylanase-encoding gene, xyn11NX, was cloned from Nesterenkonia
      xinjiangensis CCTCC AA001025 and expressed in Escherichia coli. The gene encoded
      a 192-amino acid polypeptide and a putative 50-amino acid signal peptide. The
      deduced amino acid sequence exhibited a high degree of similarity with the
      xylanases from Streptomyces thermocyaneoviolaceus (68%) and Thermobifida fusca
      (66%) belonging to glycoside hydrolase family 11. After purification to
      homogeneity, the recombinant Xyn11NX exhibited optimal activity at pH 7.0 and 55
      degrees C and remained stable at weakly acidic to alkaline pH (pH 5.0-11.0). The
      enzyme was thermostable, retaining more than 80% of the initial activity after
      incubation at 60 degrees C for 1 h and more than 40% of the activity at 90
      degrees C for 15 min. The K (m) and V (max) values for oat spelt xylan and
      birchwood xylan were 16.08 mg ml(-1) and 45.66 micromol min(-1) mg(-1) and 9.22
      mg ml(-1) and 16.05 micromol min(-1) mg(-1), respectively. The predominant
      hydrolysis products were xylobiose and xylotriose when using oat spelt xylan or
      birchwood xylan as substrate.

PMID- 19838861
TI  - Antifungal and antiproliferative activities of lectin from the rhizomes of
      Curcuma amarissima Roscoe.
AB  - A lectin was purified from the rhizomes of Curcuma amarissima Roscoe by aqueous
      extraction, fractionation with 80% saturated ammonium sulfate, and a combination
      of affinity and gel chromatography on ConA Sepharose and Superdex G-75,
      respectively. The molecular mass of the purified lectin was 32.4 kDa, as
      estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      lectin showed no significant specificity in its ability to hemagglutinate
      erythrocytes from human blood groups (A, B, AB, and O), but for other animals, it
      only agglutinated rabbit and rat, and not mouse, guinea pig, goose, and sheep
      erythrocytes. The lectin was stable at temperatures below 40 degrees C, but the
      hemagglutinating activity halved when it was heated to 45-85 degrees C and was
      completely lost at 95 degrees C. The hemagglutinating activity was more stable at
      80 degrees C than at 70 degrees C and was rapidly inactivated at 90 degrees C. It
      showed a maximum hemagglutination activity within the pH range of 8.0-11.0. The
      deduced amino acid sequence of an internal tryptic peptide sequence of this
      purified lectin showed sequence similarity (homology) to other members of the
      leucoagglutinating phytohemagglutinin precursor family, whilst the complete
      lectin inhibited the in vitro growth of three plant pathogenic fungi, Fusarium
      oxysporum, Exserohilum turicicum, and Colectrotrichum cassiicola, at a
      concentration of 17.5 to 35 microg, and showed in vitro cytotoxicity against the
      BT474 breast cancer cell line with an IC(50) of approximately 21.2 microg.

PMID- 19838862
TI  - A 22-week, multicenter, randomized, double-blind controlled trial of Crocus
      sativus in the treatment of mild-to-moderate Alzheimer's disease.
AB  - RATIONALE: There is increasing evidence to suggest the possible efficacy of
      Crocus sativus (saffron) in the management of Alzheimer's disease (AD).
      OBJECTIVE: The purpose of the present investigation was to assess the efficacy of
      C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty
      four Persian-speaking adults 55 years of age or older who were living in the
      community were eligible to participate in a 22-week, double-blind study of
      parallel groups of patients with AD. The main efficacy measures were the change
      in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical
      Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events
      (AEs) were systematically recorded. Participants were randomly assigned to
      receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day
      (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective
      similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The
      frequency of AEs was similar between saffron extract and donepezil groups with
      the exception of vomiting, which occurred significantly more frequently in the
      donepezil group. CONCLUSION: This phase II study provides preliminary evidence of
      a possible therapeutic effect of saffron extract in the treatment of patients
      with mild-to-moderate Alzheimer's disease. This trial is registered with the
      Iranian Clinical Trials Registry (IRCT138711051556N1).

PMID- 19838863
TI  - Impulsive choice and response in dopamine agonist-related impulse control
      behaviors.
AB  - RATIONALE: Dopaminergic medication-related impulse control disorders (ICDs) such
      as pathological gambling and compulsive shopping have been reported in
      Parkinson's disease (PD). HYPOTHESIS: We hypothesized that dopamine agonists
      (DAs) would be associated with greater impulsive choice or greater discounting of
      delayed rewards in PD patients with ICDs (PDI). METHODS: Fourteen PDI patients,
      14 PD controls without ICDs, and 16 medication-free matched normal controls were
      tested on the Experiential Discounting Task (EDT), a feedback-based intertemporal
      choice task, spatial working memory, and attentional set shifting. The EDT was
      used to assess choice impulsivity (hyperbolic K value), reaction time (RT), and
      decision conflict RT (the RT difference between high conflict and low conflict
      choices). PDI patients and PD controls were tested on and off DA. RESULTS: On the
      EDT, there was a group by medication interaction effect [F(1,26) = 5.62; p =
      0.03] with pairwise analyses demonstrating that DA status was associated with
      increased impulsive choice in PDI patients (p = 0.02) but not in PD controls (p =
      0.37). PDI patients also had faster RT compared to PD controls [F(1,26) = 7.51, p
      = 0.01]. DA status was associated with shorter RT [F(3,24) = 8.39, p = 0.001] and
      decision conflict RT [F(1,26) = 6.16, p = 0.02] in PDI patients but not in PD
      controls. There were no correlations between different measures of impulsivity.
      PDI patients on DA had greater spatial working memory impairments compared to PD
      controls on DA (t = 2.13, df = 26, p = 0.04). CONCLUSION: Greater impulsive
      choice, faster RT, faster decision conflict RT, and executive dysfunction may
      contribute to ICDs in PD.

PMID- 19838864
TI  - Comparison of injection methods in myofascial pain syndrome: a randomized
      controlled trial.
AB  - In this study; we aimed to compare the efficacy of local anesthetic injection and
      dry needling methods on pain, cervical range of motion (ROM), and depression in
      myofascial pain syndrome patients (MPS). This study was designed as a prospective
      randomized controlled study. Eighty patients (female 52/male 28) admitted to a
      physical medicine and rehabilitation outpatient clinic diagnosed as MPS were
      included in the study. Patients were randomly assigned into two groups. Group 1
      (n = 40) received local anesthetic injection (2 ml lidocaine of 1%) and group 2
      (n = 40) received dry injecting on trigger points. Both patient groups were given
      stretching exercises aimed at the trapezius muscle to be applied at home.
      Patients were evaluated according to pain, cervical ROM, and depression. Pain was
      assessed using Visual Analog Scale (VAS) and active cervical ROM was measured
      using goniometry. Beck Depression Inventory (BDI) was used to assess the level of
      depression. There were no statistically significant differences in the pre
      treatment evaluation parameters of the patients. There were statistically
      significant improvements in VAS, cervical ROM, and BDI scores after 4 and 12
      weeks in both groups compared to pre-treatment results (p < 0.05). No significant
      differences were observed between the groups (p > 0.05). Our study indicated that
      exercise associated with local anesthetic and dry needling injections were
      effective in decrease of pain level in MPS as well as increase of cervical ROM
      and decrease of depressive mood levels of individuals.

PMID- 19838865
TI  - The role of cuticular hydrocarbons in male mating behavior of the mustard leaf
      beetle, Phaedon cochleariae (F.).
AB  - We investigated the role that cuticular hydrocarbons (CHC) play in sexual
      communication by the mustard leaf beetle, Phaedon cochleariae (Coleoptera:
      Chrysomelidae). In laboratory bioassays, male P. cochleariae attempted to
      copulate with living or freeze-killed females as often as with males. However,
      the duration of copulation with females was longer than with males. To elucidate
      the impact of CHC on this behavior, cuticular compounds of adults of both sexes
      were extracted with dichloromethane. Male mating attempts with glass beads
      treated with the dichloromethane extract were nearly as frequent as with living
      beetles. The dichloromethane extract was fractionated by silica gel
      chromatography, and the biological activity of the fractions was tested by
      applying them to glass beads. A non-polar hexane fraction significantly elicited
      mating behavior, whereas the polar methanol fraction did not, likely because it
      contained defensive compounds from exocrine glands located in the elytra and
      pronota. Interestingly, a mixture of both the non-polar and polar fraction tended
      to elicit more mating attempts than did the non-polar hexane fraction alone.
      Further fractionation of the significantly active hexane fraction by silver
      nitrate column chromatography revealed that saturated CHC elicited mating
      behavior, but the olefins did not. GC-MS analyses of dichloromethane cuticular
      extracts showed that the male and female CHC profiles were qualitatively
      identical, but differed in their relative composition. Canonical discriminant
      analysis showed that CHC profiles of males and females formed separate clusters.
      Nevertheless, the results of our bioassays demonstrated that male and female CHC
      did not elicit sex discriminative male behavior, but induced mating by males
      regardless of the sex of the partner.

PMID- 19838866
TI  - Determination of preferred pH for root-knot nematode aggregation using pluronic F
      127 gel.
AB  - Root-knot nematodes (Meloidogyne spp.) are obligate endoparasites of a wide range
      of plant species. The infective stage is attracted strongly to and enters host
      roots at the zone of elongation, but the compounds responsible for this
      attraction have not been identified. We developed a simple assay to investigate
      nematode response to chemical gradients that uses Pluronic F-127, a synthetic
      block copolymer that, as a 23% aqueous solution, forms a liquid at low
      temperature and a gel at room temperature. Test chemicals are put into a modified
      pipette tip, or 'chemical dispenser,' and dispensers are inserted into the gel in
      which nematodes have been dispersed. Meloidogyne hapla is attracted to pH
      gradients formed by acetic acid and several other Bronsted acids and aggregates
      between pH 4.5 and 5.4. While this pH range was attractive to all tested root
      knot nematode strains and species, the level of aggregation depended on the
      species/strain assessed. For actively growing roots, the pH at the root surface
      is most acidic at the zone of elongation. This observation is consistent with the
      idea that low pH is an attractant for nematodes. Root-knot nematodes have been
      reported to be attracted to carbon dioxide, but our experiments suggest that the
      observed attraction may be due to acidification of solutions by dissolved CO(2)
      rather than to CO(2) itself. These results suggest that Pluronic F-127 gel will
      be broadly applicable for examining responses of a range of organisms to chemical
      gradients or to each other.

PMID- 19838867
TI  - Detection of sputum Aspergillus galactomannan for diagnosis of invasive pulmonary
      aspergillosis in haematological patients.
AB  - We investigated the diagnostic utility of Aspergillus galactomannan (GM) in
      sputum for diagnosis of invasive pulmonary aspergillosis (IPA) in haematologic
      patients and compared the results with those of bronchial lavage fluid (BLF) and
      serum. Patients were classified into 4 groups using modified European
      Organization for Research and Treatment of Cancer criteria: group A, proven IPA;
      group B, probable IPA; group C, possible IPA; group D, others. Groups A and B
      were considered the IPA group (n = 6); group D was considered non-IPA group (n =
      37); group C (n = 13) was equivocal for IPA. As a true negative control, sputa
      from patients with community-acquired pneumonia (CAP) without risk factors (group
      E, n = 22) were used. From the receiver-operating characteristic curves, the cut
      off levels were determined as 1.2 in sputum, 0.5-1.3 in BLF and 0.5 in serum. The
      sensitivity and specificity of sputum, BLF and serum GM were 100 and 62.2%, 66.7
      and 100%, and 83.3 and 81.1%, respectively. Twenty-two patients with CAP (group
      E) showed median GM levels in the sputa of 0.1 (range 0.0-1.0). Sputum GM is a
      useful non-invasive test for screening of IPA in haematological patients, and may
      also be useful for assessment of the risk of developing IPA.

PMID- 19838868
TI  - Accuracy of reporting current medications by cancer patients presenting to an
      emergency center.
AB  - BACKGROUND: Due to high coexistence of comorbidity, cancer patients take many
      medications and are susceptible to negative consequences of polypharmacy. To
      avoid adverse events during care transitions, patients need to correctly
      communicate their medications. The emergency center (EC) presents opportunities
      to assess patients' knowledge of medications and reconcile medication profiles.
      OBJECTIVE: The purpose was to evaluate the medication knowledge of cancer
      patients presenting to the EC and to identify factors associated with higher
      knowledge. DESIGN AND MEASUREMENTS: For the cross-sectional self-administered
      survey, 254 patients were enrolled and gave name, dose, frequency, route, and
      indication for medications. Responses were checked for accuracy against
      outpatient pharmacy dispensing records within or outside M. D. Anderson Cancer
      Center. Demographic data was obtained from medical records. For each patient, we
      calculated a patient medication knowledge (PMK-overall) score indicating
      percentage of correct responses. RESULTS: Median PMK-overall score was 80%.
      Patients who used a medication aid to fill out the survey were 6.5 times more
      likely to have a high level of medication knowledge, or PMK-overall score > or =
      80%. Predictors of using a medication aid included lower education level, solid
      tumor, more than five medications, married, and using a medication list at home.
      CONCLUSIONS: Though our findings may not be generalizable to settings outside the
      EC, we found cancer patients to have high levels of medication knowledge. Future
      studies should validate the use of PMK scores to predict medication adherence and
      other outcomes. Patients should be encouraged to use a medication aid when
      presenting information to the health care system.

PMID- 19838869
TI  - New insights into the pathogenesis of Crohn's disease: are they relevant for
      therapeutic options?
AB  - During the last few years significant advances have been achieved in the
      understanding of the pathogenesis of inflammatory bowel disease (IBD). A genetic
      susceptibility to Crohn's disease has been proven by identification of variations
      as risk factor NOD2/CARD15. Functional data on NOD2/CARD15 and NF-kappaB
      activation indicate that an inflammatory reaction of the intestinal mucosa, as an
      immediate response of the innate immune system, may be necessary for the
      maintenance of gut homeostasis. Crohn's disease is now also discussed as an
      impaired and inadequate immune reaction and no longer only as a hyper
      responsiveness of the mucosal immune system. Data on NOD2/CARD15 expression
      suggest that macrophages and epithelial cells could be the locus of the primary
      pathophysiological defect and that T-cell activation might just be a secondary
      effect inducing chronification of the inflammation, perhaps as backup mechanism
      to insufficient innate immunity. In addition to NOD2/CARD15 there are more
      "innate" pathways by which commensal and pathogenic bacteria can directly be
      hindered to invade the human body (such as interaction with Toll like receptors,
      TLRs and defensins). The "germ-concept" and the "genetic concept" of IBD
      pathophysiology are converging. However, more time is needed until these
      important insights in IBD pathogenesis will make their way into routine
      diagnostic procedures and treatment of patients with IBD.

PMID- 19838870
TI  - Targeting burn prevention in the paediatric population : a prospective study of
      children's burns in the Lausanne area.
AB  - QUESTION UNDER STUDY: Domestic accidents are an important problem in paediatric
      medicine. This study was designed to gain a better understanding of burn
      mechanisms and target prevention. METHODS: Children treated for burn lesions in
      the Department of Paediatric Surgery between August 2004 and August 2005 were
      included in this prospective study. The burn mechanisms, the children's ages and
      the circumstances in which children were burned as well as their home environment
      variables were analyzed. RESULTS: The current study included eighty-nine
      patients, aged between 2 months and 15 years. Seventy-eight percent were less
      than 5 years old. More than half were boys. Hot liquid scalding was the most
      frequent mechanism. There does not seem to be an increased risk in the immigrant
      population or in low economic status families. In most cases, an adult person was
      present at time of injury. CONCLUSIONS: If we were to describe the highest "at
      risk" candidate for a burn in our region, it would be a boy aged 15 months to 5
      years who is burned by a cup of hot liquid on his hand, at home, around mealtime,
      in the presence of one or both parents. Reduced attention in the safe domestic
      setting is probably responsible.

PMID- 19838871
TI  - Swiss national MD-PhD-program: an outcome analysis.
AB  - PURPOSE: This study aims at a first evaluation of the outcome of the Swiss
      national MD-PhD program during the last 16 years. METHOD: One hundred and twenty
      six former and current students in the Swiss national MD-PhD program were
      surveyed via a Web-based questionnaire in September 2007. Twenty-four questions
      assessed information regarding participant demographics, information on the PhD
      thesis and publication activity, current positions and research activity, as well
      as participant's opinions, attitudes and career goals. RESULTS: Eighty
      questionnaires were received from 126 MD-PhD students and graduates (63.5%
      response rate). The responders consisted of present students (36%), former
      graduates (56%), and dropouts (8%). The percentage of women in the program was
      23%, and the average duration of the program was 4.2 +/- 1.4 years. Research
      interests were predominantly in the fields of neuroscience, immunology, molecular
      biology and cancer research. A considerable portion of the MD-PhD graduates had
      an excellent publication record stemming from their PhD research work, and 89%
      were planning to continue a research-orientated career. Over 50% of those MD-PhD
      graduates completing their thesis before 2002 had already reached an assistant or
      full professor position at the time of the survey. Nearly all participants
      considered the MD-PhD training helpful to their career and high quality standards
      were assigned to the acquired practical and intellectual skills. However,
      criticism was expressed concerning the general mentoring and the career related
      mentoring. Moreover, general mentoring and career related mentoring were
      significantly less well perceived in research groups employing more than seven
      PhD students at the same time. CONCLUSIONS: The MD-PhD students and graduates
      surveyed were satisfied with their education and most of them continued a
      research-orientated career. Regarding the overall positive evaluation, this study
      supports the view that MD-PhD graduates are well qualified for a successful
      career in academic medicine.

PMID- 19838872
TI  - Glycaemic control in hospitalised diabetic patients at the University Hospital
      Basel in 2002 and in 2005.
AB  - INTRODUCTION: Hyperglycaemia has been shown to be detrimental in severely ill
      patients. Prospective randomized controlled trials in ICU patients demonstrated
      the benefit of near-normoglycaemia in reducing morbidity and mortality.
      Recommendations of professional societies (e.g., the American Diabetes
      Association) on glycaemic control in hospitalised patients have recently been
      published. It was therefore of interest to assess whether glycaemic control of
      diabetic subjects in our hospital adhered to these guidelines. No recent data are
      available on the glycaemic control of hospitalised diabetic patients in
      Switzerland. METHODS: Medical records of 580 hospitalised patients with type 1
      and type 2 diabetes (290 from 2002, 290 from 2005) were extracted from the
      internal data base of the University Hospital Basel. The selection was based on
      the charts of successive admissions each month of the year. From these 290
      records, 100 records were from the medical and surgical wards, respectively, and
      30 from the medical ICU (MICU), 30 from the surgical ICU (SICU) and 30 from the
      coronary care unit (CCU), respectively. Thereby, the quality of glycaemic control
      was assessed within and between the wards. RESULTS: HbA1c of all diabetic
      patients with available measurements was 7.6 +/- 1.8% (mean +/- SD). HbA1c in
      medical wards was higher in 2005 than in 2002 (8.5 +/- 1.9% vs 7.5 +/- 2.8%; p =
      0.014), and higher compared to surgical wards (8.5 +/- 1.9 % vs 6.7 +/- 1.1%; p
      <0.0001). On admission 60% of the plasma glucose concentrations (PGC) in medical
      and surgical wards were above the recommended limit of 8 mmol/l (10.8 +/- 7.5
      mmol/l); in 63% of the measurements in the MICU, SICU and CCU the values were
      above 6.8 mmol/l. In 2005, PGC in medical wards on admission was higher than in
      surgical wards (13.5 +/- 9.9 vs 9.4 +/- 9.9 mmol/l, p <0.0001); in the MICU PGC
      was lower than in the SICU (9.7 +/- 1.5 vs 19.5 +/- 13.9 mmol/l; p <0.0001) and
      in the CCU (9.7 +/- 1.5 vs 14.1 +/- 12.1 mmol/l; p = 0.038). PGC decreased on day
      4 compared to admission in the medical wards in 2005 (p = 0.024). In the other
      wards PGC in 2005 failed to decrease during hospitalisation. CONC:LUSION: Most
      diabetic patients admitted to the hospital remained distinctly hyperglycaemic
      during hospitalisation. This was the case even in intensive care units, where
      equipment and staff for improved glycaemic control were available and where
      strict glycaemic control has recently been demonstrated to result in decreased
      complications, mortality and length of stay.

PMID- 19838873
TI  - TGF-beta signaling in COPD: deciphering genetic and cellular susceptibilities for
      future therapeutic regimen.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of
      death in the developed world and associated with a high individual and
      socioeconomic burden. Despite emerging preventive efforts and ongoing clinical
      trials, the frequency and mortality of COPD are expected to continue to rise over
      the next decades. COPD is defined as an irreversible expiratory airflow
      limitation, which is caused by various degrees of the following two main
      features: First, small airway disease (SAD), which includes airway inflammation
      and remodelling, and second, emphysema, which is characterised by airspace
      enlargement. The major risk factor for COPD is cigarette smoke exposure; however,
      the molecular mechanisms linking smoke to different COPD features on the cellular
      level remain elusive. The transforming growth factor (TGF)-beta superfamily
      constitutes more than 40 members, which are essential during organ development, a
      process often recapitulated in chronic diseases. Emerging interest in the role of
      TGF-beta in the pathogenesis of COPD has recently evolved, particularly since
      genetic studies have demonstrated an association of gene polymorphisms of the TGF
      beta superfamily with COPD. In addition, increased expression of TGF-beta1 in
      COPD lungs and primary cells, such as epithelial cells, macrophages, or
      fibroblasts isolated from COPD specimens, was reported, suggesting an impact of
      TGF-beta signalling on the development and progression of COPD. Thus, targeted
      interventions of TGF-beta signalling may represent a suitable therapeutic option
      in COPD. In this review, we will summarise the current understanding of the
      impact of TGF-beta in COPD pathogenesis. The review is separated into five
      chapters: 1) an introduction to COPD, 2) an introduction to TGF-beta signalling,
      3) a summary of TGF-beta gene polymorphisms in COPD, 4) a summary of TGF-beta
      signalling in small airway disease, and 5) a summary of TGF-beta signalling in
      emphysema.

PMID- 19838874
TI  - Morbidity and mortality in HIV-infected individuals - a shift towards
      comorbidities.
AB  - Combination antiretroviral therapy (cART) has dramatically improved the prognosis
      of HIV-infected persons to a level close to a normal life expectancy in a
      significant proportion of treated individuals. On starting cART HIV-induced
      immune deficiency can be prevented or, if already present, reconstituted.
      Remaining morbidity and mortality is partly due to late presentation of patients,
      when CD4-T-cells have already fallen below 200 cells/microL often accompanied by
      symptomatic disease. However, at present morbidity and mortality are mainly
      related to comorbidities such as hepatitis and tumours at least partly associated
      with HIV infection. It should be noted that, as HIV-infected patients become
      older, long-term toxicity of antiretroviral drugs may play an important role in
      increasing the risk of cardiovascular diseases. The changing pattern of HIV
      associated diseases may indicate the need for specific preventive measures in
      this population.

PMID- 19838875
TI  - Asthma data from the Swiss Sentinel Surveillance Network, 1989-2005 - from
      monitoring to research.
AB  - QUESTIONS UNDER STUDY / PRINCIPLES: The Swiss Sentinel Surveillance Network
      (SSSN) has been used as a monitoring system for asthma epidemiology. Three
      aspects of asthma were studied between 1989 and 2005: the seasonal pattern of
      asthma, practice incidence and time trends for allergic and non-allergic asthma
      on the basis of the association of asthma with eczema and hay fever. The purpose
      of this report is to use the results from 17 years of asthma monitoring to show
      that the SSSN can be used as an instrument of research in practice. METHODS:
      Basically, monthly and yearly rates of episodes per 1000 consultations were
      calculated from weekly reports, and standard time series analysis methods were
      used to explore trends. RESULTS: The seasonal pattern shows distinct peaks of
      asthma attacks in June and November. Long-term trends show that consultations for
      first asthma episodes increased up to 1999 and fell thereafter. Consultations for
      subsequent asthma episodes have fallen by a third since 1994. Short-term trends
      indicate a plateau from 1997 to 2000 before a steep decline. The separate
      analysis of allergic and non-allergic asthma shows that the decrease in asthma
      consultations is chiefly due to the allergic component of asthma. CONCLUSION:
      These findings are similar to those from other studies for the same time-period
      and show that the SSSN can generate valid scientific data.

PMID- 19838876
TI  - Long-term cardiovascular and non-cardiovascular mortality in women and men with
      type 1 and type 2 diabetes mellitus: a 30-year follow-up in Switzerland.
AB  - BACKGROUND: While studies from other countries have shown an excess mortality in
      diabetic individuals when compared with the general population, comparable long
      term data is not available for Switzerland. AIMS: To assess gender-specific
      cardiovascular and non-cardiovascular mortality of patients with type 1 and type
      2 diabetes compared with the general Swiss population between 1974 and 2005.
      DESIGN: 533 patients (225 type 1, 308 type 2 diabetes, 52.2% men) were followed
      for 30 years (10349 person-years). RESULTS: Diabetic patients had an increased
      all-cause mortality compared with the general population (SMR [95% CI] 3.8 [3.5
      4.3]). Standardised mortality ratio (SMR) was higher for type 1 compared with
      type 2 diabetic patients (4.5 [3.8-5.3] vs 3.5 [3.1-4.0], p = 0.032). For
      cardiovascular and non-cardiovascular deaths SMRs were 5.6 (95% CI 4.8-6.6) and
      2.7 (2.3-3.1) and did not differ according to type of diabetes. SMRs for all
      cause and cardiovascular mortality were significantly higher in women compared
      with men in type 1 (p <0.05 and p <0.01) and type 2 diabetes (p <0.001 and p
      <0.01). In both types of diabetes, SMRs significantly decreased during the last
      two decades (p for trend 0.004 and 0.002). CONCLUSIONS: Patients with type 1 and
      type 2 diabetes had an increased long-term mortality compared with the general
      Swiss population. Excess mortality was higher in type 1 compared with type 2
      diabetes and in women compared with men for both types of diabetes, but steadily
      decreased over the last two decades.

PMID- 19838878
TI  - Teaching medical students how to break bad news: a Turkish experience.
AB  - BACKGROUND: To assess the effect of teaching breaking bad news. METHODS: The
      session incorporated brainstorming, presentation, discussion, small-group
      exercises using standardized patients. Course was evaluated through a pre
      objective structured clinical examination (OSCE), first post-OSCE (post-OSCE1),
      second post-OSCE (post-OSCE2) (6th month), and questionnaires. RESULTS: Pre-OSCE,
      post-OSCE1, post-OSCE2 scores: preparing the environment 5.83 +/- 0.23, 7.93 +/-
      0.19, 9.78 +/- 0.07; understanding what patient knows and wants to learn 1.83 +/-
      0.33, 6.47 +/- 0.27, 9.68 +/- 0.11; giving information 3.25 +/- 0.34, 7.43 +/-
      0.19, 9.67 +/- 0.10; developing empathy 2.50 +/- 0.32, 6.92 +/- 0.28, 9.87 +/-
      0.06; closing the interview 2.28 +/- 0.28, 6.98 +/- 0.25, 9.83 +/- 0.07. The
      differences between OSCEs were significant. In the questionnaire, 54.1% of 146
      students perceived more competent. CONCLUSIONS: Course seems beneficial.

PMID- 19838879
TI  - Inclusion of complementary and alternative medicine in US state comprehensive
      cancer control plans: baseline data.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) among cancer
      patients has increased substantially during the last decade. The purpose of this
      investigation is to summarize CAM content of comprehensive cancer control (CCC)
      plans in the United States, territories, and tribes. METHODS: Sixty-six CCC
      plans, including all the states, most of the territories, and nearly all the
      Native American tribes were analyzed for content of CAM, and predominant thematic
      areas were summarized. RESULTS: Thirty-nine plans (59.1%) included CAM content.
      The predominant themes identified included increased education of CAM practices
      (46.2%), followed by utilization of existing CAM providers (28.2%), increasing
      CAM research efforts (18%), encouraging patient and provider communication about
      CAM use (18%), establishment of CAM baseline data (10.3%), and CAM as a barrier
      to treatment (10.3%). CONCLUSION: CAM is an emerging area in cancer care. The
      increasing inclusion of various themes of CAM into CCC plans indicate that many
      US cancer coalitions are taking steps to include the education and promotion of
      safe and efficacious CAM therapies for cancer patients.

PMID- 19838880
TI  - A web-based assessment of pediatrics resident medical knowledge in childhood
      hereditary gastrointestinal cancer predisposing syndromes.
AB  - BACKGROUND: Pediatricians need to competently care for children with hereditary
      gastrointestinal cancer-predisposing syndromes. Pediatrics resident education on
      this subject has hithertofore never been studied. METHODS: Forty-five US
      pediatrics/internal medicine-pediatrics program directors allowed their residents
      to participate in an anonymous questionnaire. The survey-questionnaire was
      administered as a hyperlinked interactive Web page through e-mail to all
      consenting residents. RESULTS: Thirty-eight sites including 290 of 1327 residents
      (21.5%) and 33 internal medicine-pediatrics participated in the study. Knowledge
      on polyposis syndromes varied by syndrome (14% to 84% correct) but not by year of
      training. Internal medicine-pediatrics residents were more likely to inquire on
      family history including polyposis, early colorectal cancer, than pediatrics
      residents. CONCLUSIONS: This study suggests that familiarity with cancer
      syndromes does not accrue during resident training in pediatrics. The
      observations suggest that greater emphasis on resident education on these
      syndromes may improve outcomes in this vulnerable group.

PMID- 19838881
TI  - Breast cancer and cervical cancer control program enrollees inform the kin keeper
      curriculum.
AB  - BACKGROUND: The purpose of this study is to present the methodology of developing
      the Kin Keeper Cancer Prevention Curriculum Guide and Workbook through
      participatory engagement of women from underserved communities. METHODS: It was
      developed to cross train community health workers (CHWs) from public health
      programs to deliver cancer education. Data collection included review of existing
      educational materials, a 10-minute telephone survey of 146 women enrolled in a
      Breast and Cervical Cancer Control Program and a pair of pre-post training
      assessments of 31 African American, Latina, and Arab CHWs. RESULTS: The enrollees
      adequately informed the curriculum and the CHWs increased their scores by 7%
      (14%) in breast (cervical) cancer literacy; P-values <0.01. CONCLUSION: The
      methodology was validated; the curriculum was well-informed and CHWs were
      effectively cross trained using the curriculum.

PMID- 19838882
TI  - Breast cancer knowledge and barriers to mammography in a low-income managed care
      population.
AB  - BACKGROUND: Low-income women experience multiple barriers to screening
      mammography. This study explored cancer knowledge as a point of intervention to
      reduce overall barriers. METHODS: A survey of breast cancer knowledge and
      barriers was obtained from 173 low-income female residents of Middle Tennessee, >
      or =40 years, enrolled in the state managed care organization and nonadherent to
      mammography. Multiple regression models examined the effect of breast cancer
      knowledge on mammography screening barriers. RESULTS: Comprehensive breast cancer
      knowledge, not mere screening awareness, was the strongest contributor towards
      lower barrier scores. CONCLUSIONS: Strategies to overcome mammography barriers
      should include comprehensive breast cancer education.

PMID- 19838883
TI  - Training lay health workers to promote post-treatment breast cancer surveillance
      in African American breast cancer survivors: development and implementation of a
      curriculum.
AB  - BACKGROUND: African American breast cancer survivors are less adherent to
      guidelines for post-treatment breast cancer surveillance compared to White
      survivors. Survivors in Spirit (SIS) is an intervention that addresses this
      problem through lay health workers (LHWs). METHODS: African American women were
      trained as LHWs using a structured curriculum. Trainees' intervention knowledge
      was assessed before and after training. RESULTS: There was a substantial increase
      in the mean percentage of correct items from pre- to post-test for the trainees
      as a group. CONCLUSIONS: LHWs can be effectively prepared to conduct
      interventions focusing on the complexities of breast cancer recurrence and
      surveillance.

PMID- 19838884
TI  - Tobacco-free community coalitions: opportunities for enhancing oral cancer
      prevention programs.
AB  - BACKGROUND: This study identified oral cancer (OC) education and tobacco
      reduction collaboration within tobacco-free community coalitions (TFCC). METHODS:
      Data from 4 TFCC were collected via educational intervention surveys and
      structured focused group Interviews. RESULTS: Of the 52 participants, 96% were
      aware that tobacco products are risk factors for OC, yet 33% were unaware of the
      high OC impact locally. About 90% agreed that primary care providers and dentists
      should provide OC screenings and tobacco cessation. CONCLUSION: There is a need
      for provider endorsement and public demand for OC screenings. Opportunity exists
      for partnering and collaborative OC prevention with TFCC.

PMID- 19838885
TI  - Awareness of anticancer vaccines among Asian American women with limited english
      proficiency: an opportunity for improved public health communication.
AB  - BACKGROUND: Asian Americans suffer from liver and cervical cancers, both vaccine
      preventable, yet vaccine awareness has not been described. METHODS: Cross
      sectional survey (6 languages, 380 adult women). RESULTS: Those with limited
      English proficiency (LEP) were less likely to have accurate knowledge of cervical
      cancer vaccine (44% vs. 76%, among the 34% aware of any cancer-preventive
      vaccines) and were more likely to believe vaccines existed for non-vaccine
      preventable cancers. Awareness of anti-liver cancer vaccine was low for both LEP
      and non-LEP women. CONCLUSION: There is a great need to educate Asian Americans
      about vaccine-preventable cancers, especially among LEP women.

PMID- 19838886
TI  - Oncology education in Canadian undergraduate and postgraduate training programs.
AB  - BACKGROUND: We evaluated the quality of oncology education in undergraduate (UG)
      and postgraduate (PG) training programs. METHODS: We surveyed UG schools in
      medicine, nursing, and pharmacy as well as PG residencies in family and internal
      medicine to assess the programs' oncology content. RESULTS: Among 58 UG and 26 PG
      programs nationwide, response rates were 58.6% and 69.2%, respectively. Cancer
      constituted <10% of the curriculum and <10% of the final examination in 70.6% and
      58.8% of UG schools. For PG programs, most devoted more time to teaching other
      specialties: cardiology (89%), respirology (67%), nephrology (67%), and
      gastroenterology (61%). CONCLUSIONS: Oncology is underrepresented in current
      curriculums.

PMID- 19838887
TI  - A content analysis of cancer survivorship coverage in a representative sample of
      US news outlets.
AB  - BACKGROUND: Media are popular sources of cancer information, yet little is known
      about how survivors are depicted. METHODS: This study analyzes coverage of cancer
      survivors in a nationally representative sample of newspapers and television
      newscasts. Stories were coded for cancer type, gender, age, survivorship length
      and status, treatment types, and spirituality, among other variables. RESULTS:
      Media provide limited information about survivors. Also, although breast cancer
      coverage was close to survivorship rates, nearly every other cancer type was
      underreported for both incidence and survivorship rates. CONCLUSIONS: Inaccurate
      media coverage may be contributing to public misunderstanding about cancer
      survivorship.

PMID- 19838888
TI  - Theater as a tool to educate African Americans about breast cancer.
AB  - BACKGROUND: The current study examines the effectiveness of theater in educating
      African American women about breast cancer. METHODS: Four hundred and forty-eight
      participants viewed a play entitled Stealing Clouds. Employing a
      retrospective/pre-post test design and paired sample t tests, researchers
      assessed the effectiveness of theater in increasing participants' knowledge about
      breast cancer and likelihood of participating in efforts to address and reduce
      breast cancer disparities. RESULTS: Results indicated that the play succeeded in
      increasing knowledge and awareness about breast cancer and intentions to improve
      health related behaviors. CONCLUSIONS: Findings suggest that theater may be an
      effective tool in educating African Americans about breast cancer.

PMID- 19838889
TI  - Melanoma high-risk families' perceived health care provider risk communication.
AB  - BACKGROUND: Families with a melanoma history are at risk of melanoma. Melanoma
      survival improves when people are aware of their risk and ways to modify it. We
      explored at-risk families' perceived risk communication from healthcare
      providers. METHODS: Qualitative description. RESULTS: Participants perceived: (1)
      few provider discussions of melanoma risk or risk-modifying behaviors; (2) a
      desire to trust information from providers; (3) the healthcare system constrains
      communication; and (4) concerns about provider competence and caring regarding
      worrisome lesions. CONCLUSIONS: Providers should provide clear, comprehensive,
      accurate, and consistent messages about melanoma to persons at high risk;
      messages also convey competence and caring.

PMID- 19838890
TI  - "Below their notice": exploring women's subjective experiences of cancer system
      exclusion.
AB  - BACKGROUND: The experiences that marginalized breast cancer populations have in
      common are rarely considered. METHODS: The authors look across 3 qualitative
      studies to explore the experiences of older, lower-income, and Aboriginal women
      diagnosed with cancer and treated by the cancer care system in Ontario, Canada.
      RESULTS: The research examines critical moments in participants' narratives that
      parallel one another and are categorized within 2 themes: Not Getting Cancer Care
      and Not Getting Supportive Care. CONCLUSIONS: Although exploratory, the findings
      merit attention both for what they tell us about women's experiences, and because
      they suggest disparities in access to treatment and psychosocial support.

PMID- 19838891
TI  - Improving cancer knowledge and screening awareness: test of a telephone
      interviewer intervention.
AB  - BACKGROUND: Appalachian respondents were surveyed about their knowledge of cancer
      and screening intentions in a pre/post research design. METHODS: At baseline, 696
      telephone interviews were conducted of randomly selected respondents. Half were
      randomly assigned to a control group and half were provided correct information
      to incorrect responses. Four months later, respondents were re-interviewed.
      RESULTS: Provision of correct information did not produce major differences in
      the intervention group. CONCLUSIONS: Although the intervention was less effective
      than anticipated, the pilot test provided possible explanations/variables that
      educators may be able to control or incorporate as features in future studies.

PMID- 19838892
TI  - A community-based approach to translating and testing cancer literacy assessment
      tools.
AB  - BACKGROUND: To address the issue of cancer disparities among women whose first
      language is not English, researchers and public health educators are challenged
      to develop culturally and linguistically appropriate material and instruments.
      METHODS: This study documents the process used to linguistically and culturally
      translate breast and cervical cancer literacy assessment tools from English to
      Spanish and from English to Arabic by using a community-based method. RESULTS:
      Results from field testing the assessments demonstrated good reliability for
      overall cancer literacy in English (Cronbach's alpha .99), Spanish (Cronbach's
      alpha .99), and Arabic (Cronbach's alpha .81). CONCLUSION: Using a community
      based approach to translate the cancer assessments helped to insure they were
      culturally appropriate.

PMID- 19838893
TI  - In a unique position or squeezed out? The professional roles of general
      practitioners in cancer care in general and of young adult cancer patients in
      particular.
AB  - BACKGROUND: Exploring experiences of general practitioners (GPs), regarding roles
      in cancer care of young adults (YAs). METHODS: Ten qualitative interviews with
      GPs were theoretically analyzed against professional characteristics. FINDINGS:
      The GPs tended to make general statements, using everyday language, they
      experience that their patients disappear, they are seldom involved, and they lack
      knowledge. CONCLUSIONS: GPs have few experiences with YA cancer patients, but
      they have a potentially unique role in general primary cancer care if they
      develop their vocational vocabulary, relate more to relevant theory, and get a
      clearer vision of the content of the professional aspects of their work.

PMID- 19838894
TI  - The effects of peer education on university students' knowledge of breast self
      examination and health beliefs.
AB  - This study was carried out to determine the effects of peer education on breast
      self-examination (BSE) knowledge and health beliefs. 180 female university
      students were trained in BSE by the nursing students. Students instructed in
      groups by their peers showed a much higher degree of BSE knowledge. It was also
      found that perceived confidence of the students educated both individually and in
      groups increased afterward. Study results further revealed that the methods used
      for peer instruction do not affect students' sub-dimensions of health beliefs
      differently after the education.

PMID- 19838895
TI  - Sources of health information among Chinese immigrants to the Pacific Northwest.
AB  - BACKGROUND: Chinese immigrants to North America experience cancer-related health
      disparities and underutilize preventive care. Little is known about Chinese
      immigrants' sources of health information. METHODS: A population-based survey of
      Chinese immigrants was conducted in Vancouver, British Columbia, Canada and
      Seattle, Washington. RESULTS: The study group included 899 individuals. Less than
      three fourths of the respondents reported receiving health information from
      health care providers, and only a minority used the Internet as a source of
      health information. We found significant differences between the sources of
      health information in Seattle and Vancouver. CONCLUSIONS: Health educators should
      consider available media outlets as well as the characteristics of a target
      community when planning intervention programs for Chinese immigrants.

PMID- 19838896
TI  - Predictors of new screening for African American men participating in a prostate
      cancer educational program.
AB  - BACKGROUND: African American (AA) men continue to have a greater than twofold
      risk of dying from prostate cancer compared to Whites. METHODS: This community
      based intervention study employed a quasi-experimental, delayed-control (cross
      over) design with randomization at the church-level (N = 345 AA men). RESULTS:
      Logistic regression analyses revealed that the level of knowledge (b = .61, P <
      .05, Exp (B) = 1.84), the perception of risk (b = 2.99, P < .01, Exp (B) =
      19.95), and having insurance (b = 3.20, P < .01, Exp (B) = 24.65) significantly
      increased the odds of participants who needed screening getting screened during
      study. DISCUSSION: This study demonstrated the need for education, community
      involvement, and increased access to encourage minority men to obtain needed
      health screenings.

PMID- 19838897
TI  - The relationship between lung cancer patients' educational level and evaluation
      of their treatment information needs.
AB  - BACKGROUND: Understanding the information needs of lung cancer patients is
      critical to developing interventions to assist them with treatment decisions. The
      present study examined how educational level is related to lung cancer patients'
      perceptions of the importance of having their information needs met and how well
      those needs were met. METHODS: Lung cancer patients completed a needs assessment
      that evaluated treatment information needs, treatment decision satisfaction,
      coping, and life satisfaction. RESULTS: Results indicated that education did
      influence the importance ratings of information needs and influenced coping
      skills. CONCLUSIONS: Findings have implication for how doctors interact with well
      and less-educated patients.

PMID- 19838898
TI  - Beliefs about heritability of cancer and health information seeking and
      preventive behaviors.
AB  - BACKGROUND: Individuals' beliefs about cancer heritability could affect their
      health information seeking and health behaviors. METHODS: Data from 5813 English
      speaking adult respondents to the 2003 Health Information National Trends Survey
      were analyzed. RESULTS: Individuals who believed that knowledge of family history
      or genes can reduce cancer risk were significantly more likely to have ever
      looked for cancer information. Ever smokers who believed that genes are the main
      cause of lung cancer were significantly more likely to smoke currently.
      CONCLUSIONS: Patients need to be educated about genetic susceptibility to cancer
      in ways that support information seeking and engagement in protective behaviors.

PMID- 19838899
TI  - Appalachian knowledge of cancer and screening intentions.
AB  - BACKGROUND: This cross-sectional study was designed to assess levels of knowledge
      about cancer and behavioral intentions regarding cancer screening from a
      representative sample of adults residing in 51 Appalachian counties in Kentucky.
      METHODS: A random-digit-dialed telephone survey obtained 696 interviews and
      provided a 4% margin of error. RESULTS: Findings showed that knowledge of cancer
      screening was generally low and uniform by age and educational attainment.
      Logistic regression models demonstrated that possessing insurance was an
      important predictor of those likely to obtain cancer screening. CONCLUSIONS:
      Having a family history of breast cancer or a family history of prostate cancer
      were not significant predictors for obtaining mammograms or prostate-specific
      antigen (PSA) tests.

PMID- 19838901
TI  - How to win a career achievement award in five easy lessons.
AB  - This professional autobiography is based on a talk given as the recipient of the
      2009 Bruno Klopfer Distinguished Contribution Award. It includes a discussion of
      5 of my habits that might be useful as a guide for future awardees including 1.
      send everything that you write to everyone you know (and ask for their help); 2.
      don't be afraid to pick up what's been dropped by others; 3. don't be afraid to
      go away and then to stay away a long time; and 4. remember good ideas--they can
      be useful in the future. For the fifth and most important lesson, one must read
      the article.

PMID- 19838902
TI  - Testing the effectiveness of family therapeutic assessment: a case study using a
      time-series design.
AB  - We describe a family Therapeutic Assessment (TA) case study employing 2
      assessors, 2 assessment rooms, and a video link. In the study, we employed a
      daily measures time-series design with a pretreatment baseline and follow-up
      period to examine the family TA treatment model. In addition to being an
      illustrative addition to a number of clinical reports suggesting the efficacy of
      family TA, this study is the first to apply a case-based time-series design to
      test whether family TA leads to clinical improvement and also illustrates when
      that improvement occurs. Results support the trajectory of change proposed by
      Finn (2007), the TA model's creator, who posits that benefits continue beyond the
      formal treatment itself.

PMID- 19838903
TI  - Construct validity of the relationship profile test: correlates of
      overdependence, detachment, and healthy dependency in low income urban women
      seeking medical services.
AB  - Studies have documented the construct validity of Bornstein and Languirand's
      (2003) Relationship Profile Test (RPT) in college students, psychotherapy
      patients, and nursing home residents, but no studies have examined the utility of
      RPT Destructive Overdependence (DO), Dysfunctional Detachment (DD), and Healthy
      Dependency (HD) scores in community samples. To fill this gap, we assessed links
      between RPT scores and theoretically related variables in low income urban women
      seeking medical services (N = 110), obtaining predicted links between RPT scores
      and scores on measures of childhood abuse and neglect, adult attachment style,
      conflict-resolution tactics involving a domestic partner, Axis I symptomatology,
      and overall quality of life. Comparison of RPT means in this sample with those in
      Bornstein et al.'s (2003) college student sample yielded differences that were
      generally in line with expectations. These results support the construct validity
      of RPT scores in urban women and suggest that the RPT may be a useful index of
      DO, DD, and HD in this heretofore unexamined population.

PMID- 19838904
TI  - Cross-national replication of the gender identity interview for children.
AB  - We administered the Gender Identity Interview for Children, a 12-item child
      informant measure, to children referred clinically for gender identity problems
      in Toronto, Ontario, Canada (N = 329) and Amsterdam, The Netherlands (N = 228)
      and 173 control children. Confirmatory factor analysis identified a Cognitive
      Gender Confusion factor (4 items) and an Affective Gender Confusion factor (8
      items). Patients from both clinics had a significantly higher deviant total score
      than the controls, and the Dutch patients had a significantly higher deviant
      score than the Toronto patients. In this cross-national study, we are the first
      to report on the validity of this measure to discriminate children with gender
      identity disorder from controls outside of North America.

PMID- 19838905
TI  - Faking good on the MCMI-III: implications for child custody evaluations.
AB  - Individuals administered the MCMI-III (Millon, Davis, & Millon, 1997) as part of
      a custody evaluation have shown elevations on the Desirability (Y), Histrionic
      (4), Narcissistic (5), and Compulsive (7) scales and low scores on the Debasement
      (Z) scale (McCann et al., 2001) and all other personality and clinical scales. In
      this experiment, we instructed participants (N = 138) to look like good parents
      (fake good) or to answer honestly. The fake-good group scored higher than the
      honest group on Y, 4, 5, and 7 and lower on scale Z and most other scales. We
      plotted the mean scale scores of our fake-good group against those of McCann et
      al.'s custody litigants and found the 2 profiles to be very closely matched and
      very different from our answer-honestly group's profile. These findings raise the
      possibility that scale elevations on 4, 5, and 7 by custody litigants are
      artifacts of faking good rather than pathology in those areas. Assessors should
      interpret this profile cautiously in custody evaluations.

PMID- 19838906
TI  - Measuring clarity of and attention to emotions.
AB  - Previous research has found that understanding one's emotions and attending to
      them are 2 dimensions of emotional awareness. In this research, we examined
      whether improved subscales for measuring clarity of and attention to emotions
      could be developed by selecting the best items from 2 frequently used measures of
      emotional awareness. Using multidimensional scaling and confirmatory factor
      analysis, we analyzed the Toronto Alexithymia Scale-20 (Bagby, Parker, & Taylor,
      1994) and the Trait Meta-Mood Scale (Salovey, Mayer, Goldman, Turvey, & Palfai,
      1995) data from 867 college students. Results supported distinct clarity and
      attention constructs. New subscales were internally consistent and fared as well
      as or better than previous versions in terms of internal consistency and
      convergent validity.

PMID- 19838907
TI  - Measuring individual differences in trait sympathy: instrument construction and
      validation.
AB  - In 3 studies, I report on the construction and validation of a multifaceted, self
      report measure of an individual's tendency to experience feelings of sorrow or
      concern for the suffering of others. The Trait Sympathy Scales (TSS) displayed
      solid properties of reliability (Studies 1-3), content validity (Study 1),
      factorial validity (Study 1), construct-related validity (Studies 1-3),
      convergent and discriminant validity (Study 2), as well as predictive validity
      (Study 3). Findings support the TSS as a sound instrument that offers several
      advantages over Davis's (1980) Empathic Concern subscale.

PMID- 19838908
TI  - Validity and stability of the youth psychopathic traits inventory in a
      nonforensic sample of young adults.
AB  - We assessed the validity and stability of the Swedish developed Youth
      Psychopathic Traits Inventory (YPI; Andershed, Kerr, Stattin, & Levander, 2002)
      in Canadian nonforensic young adults. In Study 1, a total of 217 undergraduates
      completed the YPI as well as the Psychopathic Personality Inventory-Revised (PPI
      R; Lilienfeld & Widows, 2005) and the Levenson Self-Report Psychopathy Scale
      (LSRP; Levenson, Kiehl, & Fitzpatrick, 1995). These measures were completed
      twice, with a mean of 28 days between administrations. Total YPI was strongly
      correlated with the PPI-R but also with the LSRP subscales. YPI higher order
      dimensions were meaningfully correlated with PPI-R dimensions of similar content.
      The YPI yielded fairly high temporal stability and was similar to the PPI-R and
      LSRP Primary Psychopathy scale. Using 111 undergraduates, in Study 2, we found
      the YPI was positively associated with antisocial attitudes and impulsivity and
      negatively associated with agreeableness and conscientiousness. This research
      extends the validity of the YPI beyond adolescents to Canadian young adults from
      nonforensic settings. Given its promise as a measure of psychopathic traits in
      adolescents and young adults, the YPI may prove useful in longitudinal research
      across these developmental periods.

PMID- 19838909
TI  - Investigating the MMPI-2 trauma profile in treatment-seeking peacekeepers.
AB  - Most available research on MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, &
      Kaemmer, 1989) scores in combat veterans suffering from posttraumatic stress
      disorder (PTSD) has focused on Vietnam veterans. No data are available from
      peacekeepers suffering from PTSD. The aim of this study was to investigate the
      relationship between PTSD and the MMPI-2 in a sample of 120 treatment seeking
      peacekeeping veterans. Results show that relative to a non-PTSD reference group,
      veterans who screened positive for PTSD scored higher on Scales F, 2 (D), 4 (Pd),
      6 (Pa), 7 (Pt), 8 (Sc), and 0 (Si) of the MMPI-2. Scales 2 (D), 7 (Pt), and 8
      (Sc) were highest in the mean PTSD profile but no 2- or 3-point code type could
      be defined. Moderate correlations were found between a self-report measure for
      PTSD symptoms and scores on MMPI-2 clinical scales 1 (Hs), 2 (D), 6 (Pa), 7 (Pt),
      and 8 (Sc). The MMPI-2 proved to be useful in assessing the broad range of
      symptoms typically present in trauma populations as well as the severity of
      posttraumatic morbidity.

PMID- 19838910
TI  - The Rorschach texture response: a construct validation study using attachment
      theory.
AB  - Using attachment theory, in this research, we explored the construct validity of
      the Rorschach (Exner, 1974) Texture (T) response as a measure of interpersonal
      closeness and contact. A total of 40 men and 39 women completed the Rorschach and
      2 attachment inventories. Their romantic partners also completed an informant
      version of the attachment measures. Attachment styles were measured by factor
      scores involving both self-report and partner report. Results indicate that
      attachment theory, as a broad conceptual framework, is associated with T.
      Specifically, T = 1 is most closely associated with a secure attachment style, T
      > 1 with aspects of the preoccupied style, and T = 0 with aspects of the avoidant
      style and an absence of secure attachment. Needs for closeness and contact
      associated with T can be couched within an adult attachment theory, but in this
      study, we did not test for problematic aspects of insecure attachment. Gender is
      a complicating factor and deserves more study.

PMID- 19838912
TI  - Why are there limits on theory of mind use? Evidence from adults' ability to
      follow instructions from an ignorant speaker.
AB  - Keysar et al. (Keysar, Barr, Balin, & Brauner, 2000; Keysar, Lin, & Barr, 2003)
      report that adults frequently failed to use their conceptual competence for
      theory of mind (ToM) in an online communication game where they needed to take
      account of a speaker's perspective. The current research reports 3 experiments
      investigating the cognitive processes contributing to adults' errors. In
      Experiments 1 and 2 the frequency of adults' failure to use ToM was unaffected by
      perspective switching. In Experiment 3 adults made more errors when interpreting
      instructions according to the speaker's perspective than according to an
      arbitrary rule. We suggest that adults are efficient at switching perspectives,
      but that actually using what another person knows to interpret what they say is
      relatively inefficient, giving rise to egocentric errors during communication.

PMID- 19838913
TI  - A possible link between iron deficiency and gastrointestinal carcinogenesis.
AB  - There is definitive evidence that iron overload induces oxidative stress and DNA
      damage, which can enhance carcinogenic risk. However, other evidence suggests
      that iron deficiency and anemia also increase oxidative stress and DNA damage,
      which might increase carcinogenesis risk, especially in the gastrointestinal (GI)
      tract. The aim of this review is to provide essential background information for
      the accurate interpretation of future research on iron deficiency and increased
      GI cancer risk. Based on clinical, epidemiological, and experimental evidence, we
      discuss how iron deficiency might contribute to increased cancer risk through the
      impairment of several iron-dependent metabolic functions that are related to
      genome protection and maintenance (e.g., immune responses against cancer
      initiated cells, metabolism of toxic compounds, and redox regulation of DNA
      biosynthesis and repair). Some epidemiological studies have indicated increased
      risk of GI tumors among individuals with low iron intake or low somatic iron
      stores, and in vivo data from rodent cancer models indicates the early
      progression of GI tumors during iron deficiency. Given the preliminary but
      consistent evidence relating iron deficiency to cancer risk and the fact that
      iron deficiency affects about one third of the world's population, further
      studies are needed to define the extent to which iron deficiency might increase
      GI cancer risk.

PMID- 19838914
TI  - Associations between trans fatty acid consumption and colon cancer among Whites
      and African Americans in the North Carolina colon cancer study I.
AB  - Disparities in incidence and mortality rates of colon cancer exist between Whites
      and African Americans. Prior studies examined the association between trans fatty
      acid consumption and colorectal cancer, but none assessed this possible
      relationship within a large study population of African Americans and Whites.
      Using data from a population-based, case-control study in North Carolina, we
      investigated this association with attention to possible racial differences.
      Cases and matched controls were queried on demographic characteristics, lifestyle
      factors, medical history, and diet. Cases reported higher daily consumption
      (g/day) of trans fatty acids (mean = 5.9, SD = 2.9, median = 5.5, IQR = 3.8-7.5)
      compared to controls (mean = 5.2, SD = 2.4, median = 4.7, IQR = 3.5-6.4). Energy
      adjusted trans fatty acid consumption was not associated with colon cancer.
      Compared to participants in the lowest quartile of consumption, those in the
      highest quartile had an adjusted odds ratio of 1.01 (95% confidence interval
      0.69, 1.49) for Whites and 0.99 (95% confidence interval 0.61, 1.62) for African
      Americans. No association was found between increased consumption of trans fatty
      acid and specific tumor location (proximal or distal colon). In conclusion, trans
      fatty acid consumption is not associated with colon cancer and does not
      contribute to disparities in colon cancer rates.

PMID- 19838916
TI  - Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic
      polymorphism of related enzymes, and risk of breast cancer: a case-control study
      in Japan.
AB  - We investigated associations among intake of folate, vitamin B2, vitamin B6,
      vitamin B12, and polymorphisms of 5,10-methylenetetrahydrofolate reductase
      (MTHFR) and methionine synthase (MTR) genes and breast cancer risk in a Japanese
      population. A hospital based, case-control study was conducted in Nagano
      Prefecture, Japan, in 388 pairs of patients with histologically confirmed
      invasive breast cancer and age- and area-matched controls selected from medical
      checkup examinees. Energy-adjusted intakes of folate and other B vitamins were
      derived from a validated food frequency questionnaire. Genotyping was completed
      for MTHFR (C677T and A1298T) and MTR (A2756G). Odds ratios and 95% confidence
      intervals were calculated by the conditional logistical regression model. Median
      dietary folate intake (microg/day) in the control group was 438.2 (interquartile
      range: 354.9-542.9). Neither dietary intake of folate, vitamin B2, vitamin B6, or
      vitamin B12 nor polymorphisms of MTHFR or MTR genes were significantly associated
      with breast cancer risk. Further, no significant interaction was found among
      nutrients, polymorphisms, and breast cancer risk. Associations of nutrients with
      breast cancer risk did not differ by hormone receptors status. We conclude that
      dietary intake of folate and related B vitamins and genotypes of MTHFR or MTR
      have no overall association with breast cancer risk in Japanese women.

PMID- 19838915
TI  - Well-done meat intake, heterocyclic amine exposure, and cancer risk.
AB  - High intake of meat, particularly red and processed meat, has been associated
      with an increased risk of a number of common cancers such as breast, colorectum,
      and prostate in many epidemiological studies. Heterocyclic amines (HCAs) are a
      group of mutagenic compounds found in cooked meats, particularly well-done meats.
      HCAs are some of most potent mutagens detected using the Ames/salmonella tests
      and have been clearly shown to induce tumors in experimental animal models. Over
      the past 10 years, an increasing number of epidemiological studies have evaluated
      the association of well-done meat intake and meat carcinogen exposure with cancer
      risk. The results from these epidemiologic studies were evaluated and summarized
      in this review. The majority of these studies have shown that high intake of well
      done meat and high exposure to meat carcinogens, particularly HCAs, may increase
      the risk of human cancer.

PMID- 19838918
TI  - A case-control study on fat-to-muscle ratio and risk of breast cancer.
AB  - Our objective was to analyze detailed anthropometric characterization for risk of
      breast cancer in Uruguayan women. The design was a case-control study. The
      setting was Pereira Rossell Women's Hospital, Montevideo, Uruguay. Subjects were
      343 incident breast cancer cases and 1,042 frequency-matched healthy controls who
      were interviewed on menstrual and reproductive story; and a series of skin folds,
      circumferences, and diameters were measured to calculate fat and muscle fractions
      and the derived fat-to-muscle ratio (FMR). Odds ratio (ORs) coefficients were
      taken as estimates of relative risk derived from unconditional logistic
      regression. Muscle fraction was negatively associated with risk [OR for highest
      quartile = 0.23, 95% confidence interval (CI) = 0.15-0.34], fat fraction was
      positively associated (OR = 3.90, 95% CI = 2.62-5.80), and FMR was positively
      associated (OR = 4.45, 95% CI = 2.99-6.62). Stratified analyses by body mass
      index levels also showed risk increases for the highest tertiles of FMR, always
      displaying significant linear trends. Since increases of risk were found in
      overweight and in normal weight women, results suggest that fractions and amount
      of muscle and fat components might be risk factors for breast cancer on the basis
      of currently existing metabolic and immune interrelationships between adipose and
      muscular tissue given by glutamine, exercise-derived myokines, and other
      cytokines produced by these tissues.

PMID- 19838917
TI  - Physical activity, diet, and pancreatic cancer: a population-based, case-control
      study in Minnesota.
AB  - Although mounting evidence suggests that insulin resistance is involved in
      pancreatic carcinogenesis, few epidemiologic studies have comprehensively
      investigated the role of lifestyle factors influencing this metabolic disorder in
      the etiology of pancreatic cancer. We sought to examine this problem in a case
      control study conducted in 1994-1998 in Minnesota. Cases (n = 186), aged 20 yr or
      older, were ascertained from all hospitals in the metropolitan area of the Twin
      Cities and the Mayo Clinic; from the latter, only cases residing in the Upper
      Midwest of the United States were recruited. Controls (n = 554) were randomly
      selected from the general population and frequency matched to cases by age
      (within 5 yr) and sex. Odds ratios (OR) and 95% confidence intervals (95% CI)
      were estimated using unconditional logistic regression. After adjustment for
      confounders, physical activity was associated with a reduced risk, but this
      protective effect was confined to light activity and moderate activity only (OR =
      0.55, 95% CI = 0.30-0.97, P(trend) = 0.038 and OR = 0.51, 95% CI = 0.28-0.93,
      P(trend) = 0.07, for highest vs. lowest quartile, respectively). An increased
      risk was found for dietary intakes of energy and fat but was statistically
      significant for saturated and polyunsaturated fat only. Of note, no appreciable
      difference in the magnitude of the associations existed between saturated,
      monounsaturated, and polyunsaturated fat. Compared with individuals in the lowest
      quartile of fiber intake, the risk was approximately halved for those in the
      third (OR = 0.49, 95% CI = 0.26-0.94) and the highest quartile (OR = 0.52, 95% CI
      = 0.21-1.30). Our study lends support to the hypothesis that dietary and other
      lifestyle factors influencing insulin resistance modulate pancreatic cancer risk.

PMID- 19838919
TI  - Patterns of food and nutrient consumption in northern Iran, a high-risk area for
      esophageal cancer.
AB  - Our objectives were to investigate patterns of food and nutrient consumption in
      Golestan province, a high-incidence area for esophageal cancer (EC) in northern
      Iran. Twelve 24-h dietary recalls were administered during a 1-yr period to 131
      healthy participants in a pilot cohort study. We compare here nutrient intake in
      Golestan with recommended daily allowances (RDAs) and lowest threshold intakes
      (LTIs). We also compare the intake of 27 food groups and nutrients among several
      population subgroups using mean values from the 12 recalls. Rural women had a
      very low level of vitamin intake, which was even lower than LTIs (P < 0.01).
      Daily intake of vitamins A and C was lower than LTI in 67% and 73% of rural
      women, respectively. Among rural men, the vitamin intakes were not significantly
      different from LTIs. Among urban women, the vitamin intakes were significantly
      lower than RDAs but were significantly higher than LTIs. Among urban men, the
      intakes were not significantly different from RDAs. Compared to urban dwellers,
      intake of most food groups and nutrients, including vitamins, was significantly
      lower among rural dwellers. In terms of vitamin intake, no significant difference
      was observed between Turkmen and non-Turkmen ethnics. The severe deficiency in
      vitamin intake among women and rural dwellers and marked differences in nutrient
      intake between rural and urban dwellers may contribute to the observed
      epidemiological pattern of EC in Golestan, with high incidence rates among women
      and people with low socioeconomic status and the highest incidence rate among
      rural women.

PMID- 19838920
TI  - Obesity and the associated mediators leptin, estrogen and IGF-I enhance the cell
      proliferation and early tumorigenesis of breast cancer cells.
AB  - Breast cancer continues to be a major cause of cancer deaths in women. Estrogen,
      which is also produced by the adipose tissue, is held responsible for the
      elevated risk of breast cancer in obese women. However, the adipose tissue
      secrets hormones and adipokines such as leptin and IGF-I and these substances
      could also contribute to an increased breast cancer risk for obese women. In this
      study, the impact of obesity on cell proliferation was investigated. The
      carcinogen 7, 12, dimethylbenz[a]anthracene (DMBA) was administered to normal
      weight and diet-induced obese female Sprague-Dawley rats. Cell proliferation was
      evaluated by immunohistological staining of BrdU-incorporation. In the mammary
      glands and inguinal lymphatic nodes of the obese rats, cell proliferation was
      significantly increased, indicating a significant influence of obesity on breast
      cancer. Effects of leptin, estrogen, and IGF-I on the proliferation of MCF-7
      cells in vitro were assessed using an MTT assay. Cell culture experiments
      demonstrated a mitogenic role of these three mediators on cell proliferation. Our
      data demonstrate a stimulative effect of substances produced by the adipose
      tissue on breast cancer. Body weight specific cell proliferation suggests that
      obesity-related adipokines and mediators enhance cell proliferation and increase
      the risk for breast cancer.

PMID- 19838921
TI  - Dietary isothiocyanates, glutathione S-transferase M1 (GSTM1), and lung cancer
      risk in African Americans and Caucasians from Los Angeles County, California.
AB  - Isothiocyanates, found in cruciferous vegetables, are anticarcinogenic. Racial
      differences in smoking do not fully account for the African-American excess lung
      cancer incidence. African Americans consume more cruciferous vegetables than U.S.
      Whites. Impact on lung cancer risk is unknown. The glutathione S transferase M1
      (GSTM1) gene promotes urinary isothiocyanate excretion. We evaluated dietary
      isothiocyanates and lung cancer using a population-based case-control study of
      933 African Americans and Caucasians (non-Hispanic U.S. White) from Los Angeles
      County, California (311 cases; 622 controls). Broccoli, cauliflower, greens, and
      cabbage food-frequency variables represented isothiocyanates. Isothiocyanates
      were protective for lung cancer risk. Adjusted odds ratio (OR) for the uppermost
      quartile > 80 micro mol isothiocyanates/wk, compared to lowest, was 0.65 [95%
      confidence interval (CI) = 0.41-1.00, trend P = 0.02]. Association was stronger
      among subjects with homozygous deletion of GSTM1 (OR = 0.52, 95% CI = 0.31-0.86)
      than subjects with at least one GSTM1 copy (OR = 0.77, 95% CI = 0.49-1.21). The
      difference was not statistically significant (P = 0.16). Despite African
      Americans consuming more cruciferous vegetables, the isothiocyanate association
      did not vary by race (P = 0.52). Reduced lung cancer risk with higher
      isothiocyanate intake may be slightly stronger among subjects with deletion of
      GSTM1.

PMID- 19838922
TI  - Correlation between serum phospholipid fatty acids and dietary intakes assessed a
      few years earlier.
AB  - The fatty acid composition of serum phospholipids has been shown to reflect
      dietary intakes in the previous weeks or months. However, how serum phospholipids
      relate to fatty acid intakes over a few years has hardly been examined. We
      designed a cross-sectional study within the E3N cohort, the French component of
      the European Prospective Investigation into Cancer and Nutrition in which female
      participants completed a 208-item diet history questionnaire in 1993-1995 and
      provided blood samples in 1995-1998. The study included 1,114 women who were free
      of cancer at the time of blood collection. Serum phospholipid fatty acid
      composition was assessed by capillary gas chromatography. Partial Spearman
      correlations adjusted for age and body mass index showed weak to moderate,
      although statistically significant, positive associations between dietary and
      serum oleic, linoleic, arachidonic, eicosapentaenoic, and docosahexaenoic acids.
      Moreover, serum oleic acid was directly associated with olive oil, linoleic acid
      with sunflower oil, pentadecanoic acid with dairy products, long-chain n-3 fatty
      acids with fatty fish, and trans-monounsaturated fatty acids with manufactured
      foods. In conclusion, serum phospholipid pentadecanoic acid, oleic, trans
      monounsaturated, and polyunsaturated fatty acids are suitable biomarkers for
      usual dietary intakes, although the association may weaken as the time lag
      between dietary assessment and blood collection increases.

PMID- 19838923
TI  - In vitro measures used to predict anticancer activity of apple cultivars and
      their comparison to outcomes from a rat model of experimentally induced breast
      cancer.
AB  - Experiments reported herein tested the hypothesis that cultivars of apple (Malus
      domestica Borkh.) would demonstrate anticancer activity in vivo as predicted by
      in vitro measures. Freeze dried powders of Red Delicious (RD), Fuji (FJ), Golden
      Delicious (GD), and Granny Smith (GS) apple cultivars were evaluated. Significant
      differences were noted among cultivars in total phenolics (P < 0.0001),
      flavonoids (P < 0.0003), oxygen radical absorbance capacity (P < 0.0001), and
      growth inhibition in the MDA-MB-468 human breast cancer cell line relative to
      vehicle-treated cells (P < 0.0001). These findings were extended to predict
      inhibition of the postinitiation phase of 1-methyl-1-nitrosourea-induced mammary
      carcinogenesis by freeze-dried whole apple powders of the same cultivars.
      Although rats fed apple-containing diets did not have lower incidence or
      multiplicity of cancers than rats fed control diet, a finding consistent with
      epidemiological reports on fruit and breast cancer risk, differences among
      cultivars were noted, with the greatest difference in cancer multiplicity between
      GS and RD (1.46 vs. 2.47 cancers/rat; P = 0.0159). The rate of cell proliferation
      in mammary carcinomas differed between GS and RD (P < 0.001), whereas the
      apoptotic rate did not. These findings suggest altered methodology for screening
      apples for anticancer activity and that more diverse apple cultivars with higher
      phytochemical content should be evaluated.

PMID- 19838924
TI  - Combined methionine deprivation and chloroethylnitrosourea have time-dependent
      therapeutic synergy on melanoma tumors that NMR spectroscopy-based metabolomics
      explains by methionine and phospholipid metabolism reprogramming.
AB  - Methionine (Met) deprivation stress (MDS) is proposed in association with
      chemotherapy in the treatment of some cancers. A synergistic effect of this
      combination is generally acknowledged. However, little is known on the mechanism
      of the response to this therapeutic strategy. A model of B16 melanoma tumor in
      vivo was treated by MDS alone and in combination with chloroethylnitrosourea
      (CENU). It was applied recent developments in proton-NMR spectroscopy-based
      metabolomics for providing information on the metabolic response of tumors to MDS
      and combination with chemotherapy. MDS inhibited tumor growth during the
      deprivation period and growth resumption thereafter. The combination of MDS with
      CENU induced an effective time-dependent synergy on growth inhibition. Metabolite
      profiling during MDS showed a decreased Met content (P < 0.01) despite the
      preservation of the protein content, disorders in sulfur-containing amino acids,
      glutamine/proline, and phospholipid metabolism [increase of
      glycerophosphorylcholine (P < 0.01), decrease in phosphocholine (P < 0.05)]. The
      metabolic profile of MDS combined with CENU and ANOVA analysis revealed the
      implication of Met and phospholipid metabolism in the observed synergy, which may
      be interpreted as a Met-sparing metabolic reprogramming of tumors. It follows
      that combination therapy of MDS with CENU seems to intensify adaptive processes,
      which may set limitations to this therapeutic strategy.

PMID- 19838925
TI  - The effect of Scutellaria baicalensis on the signaling network in hepatocellular
      carcinoma cells.
AB  - Scutellaria baicalensis is an anti-inflammatory and antineoplastic Chinese herbal
      therapy. We have previously shown that S. baicalensis can inhibit hepatocellular
      carcinoma (HCC) cell growth in vitro. In this study, we sought to determine the
      effect of S. baicalensis on the cell signaling network using our newly developed
      Pathway Array technology, which screens cell signaling pathways involved in cell
      cycle regulation. The HCC cell line (HepG2) was treated with S. baicalensis
      extract in vitro. The effect on the cell cycle was analyzed by flow cytometry,
      and the expression of various signaling proteins was assayed with Pathway Array.
      Our results indicate that S. baicalensis exerts a strong growth inhibition of the
      HepG2 cells via G(2)/M phase arrest. The Pathway Array analysis of 56 proteins
      revealed a total of 14 differentially expressed proteins or phosphorylations
      after treatment. Of these, 9 showed a dose-dependent decrease (p53, ETS1, Cdc25B,
      p63, EGFR, ERK1/2, XIAP, HIF-2alpha, and Cdc25C) whereas one demonstrated a dose
      dependent increase (Cyclin E) after treatment with 200 microg/ml of S.
      baicalensis. Using computer simulation software, we identified additional hubs in
      the signaling network activated by S. baicalensis. These results indicate that S.
      baicalensis exerts a broad effect on cell signaling networks leading to a
      collective inhibition of cell proliferation.

PMID- 19838926
TI  - Macelignan: a new modulator of P-glycoprotein in multidrug-resistant cancer
      cells.
AB  - The effect of macelignan, a phytoestrogen, on P-gp function was investigated
      using multidrug resistant cancer cells overexpressing P-gp (NCI/ADR-RES) and the
      fluorescent P-gp substrates, daunorubicin and rhodamine 123. Macelignan (40
      microM) increased the cellular accumulation of daunorubicin by approximately
      threefold in NCI/ADR-RES cells, whereas it did not alter the cellular
      accumulation of daunorubicin in MCF-7/sensitive cells. Similarly, the presence of
      macelignan also enhanced significantly (P < 0.05) the cellular accumulation of
      rhodamine 123 in a concentration-dependent manner in NCI/ADR-RES cells.
      Furthermore, cancer cells were more susceptible to the cytotoxicity of
      vinblastine, a P-gp substrate, in the presence of macelignan. Those results
      suggest that macelignan has inhibitory effects on P-gp mediated cellular efflux.
      However, P-gp activity did not affect the cellular accumulation of macelignan
      itself. Taken all together, macelignan was identified as a novel inhibitor of P
      gp activity and may be a promising lead compound for the rational design of more
      efficacious drugs to reverse multidrug resistance in cancer.

PMID- 19838927
TI  - Curcumin synergizes with resveratrol to inhibit colon cancer.
AB  - Development and progression of many malignancies, including colorectal cancer,
      are associated with activation of multiple signaling pathways. Therefore,
      inhibition of these signaling pathways with noncytotoxic natural products
      represents a logical preventive and/or therapeutic approach for colon cancer.
      Curcumin and resveratrol, both of which inhibit the growth of transformed cells
      and colon carcinogenesis, were selected to examine whether combining them would
      be an effective preventive and/or therapeutic strategy for colon cancer. Indeed,
      the combination of curcumin and resveratrol was found to be more effective in
      inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116
      cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells
      than either agent alone. Analysis by Calcusyn software showed synergism between
      curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or
      resveratrol was associated with the reduction in proliferation and stimulation of
      apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have
      further demonstrated that the combinatorial treatment caused a greater inhibition
      of constitutive activation of EGFR and its family members as well as IGF-1R. Our
      current data suggest that the combination of curcumin and resveratrol could be an
      effective preventive/therapeutic strategy for colon cancer.

PMID- 19838929
TI  - Salvia fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and
      inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK
      pathway.
AB  - Epidemiological studies have shown that nutrition is a key factor in modulating
      sporadic colorectal carcinoma (CRC) risk. Aromatic plants of the genus Salvia
      (sage) have been attributed many medicinal properties, which include anticancer
      activity. In the present study, the antiproliferative and proapoptotic effects of
      water extracts of Salvia fruticosa (SF) and Salvia officinalis (SO) and of their
      main phenolic compound rosmarinic acid (RA) were evaluated in two human colon
      carcinoma-derived cell lines, HCT15 and CO115, which have different mutations in
      the MAPK/ERK and PI3K/Akt signalling pathways. These pathways are commonly
      altered in CRC, leading to increased proliferation and inhibition of apoptosis.
      Our results show that SF, SO, and RA induce apoptosis in both cell lines, whereas
      cell proliferation was inhibited by the two sage extracts only in HCT15. SO, SF,
      and RA inhibited ERK phosphorylation in HCT15 and had no effects on Akt
      phosphorylation in CO115 cells. The activity of sage extracts seems to be due, at
      least in part, to the inhibition of MAPK/ERK pathway.

PMID- 19838930
TI  - Cancer protective properties of cocoa: a review of the epidemiologic evidence.
AB  - Due to their high concentration of catechins and procyanidins, bioactive
      compounds with distinct properties, cocoa and chocolate products may have
      beneficial health effects against oxidative stress and chronic inflammation, risk
      factors for cancer and other chronic diseases. This review focuses on the
      epidemiologic evidence for protective effects against cancer and overall
      mortality. The very small number of observational epidemiologic studies offers
      weak support for a reduction in mortality and little data related to cancer,
      whereas several intervention studies, despite their short duration, have reported
      some favorable changes in biomarkers assessing antioxidant status but very few
      findings related to inflammatory markers. In moderation, cocoa products may offer
      strong antioxidant effects in combination with a pleasurable eating experience.
      The benign profile of its fatty acids in combination with the low content of
      sugar of dark chocolate should lessen concerns about the adverse effects of cocoa
      products. Future nutritional trials need to assess a larger number of biomarkers
      that may be relevant for cancer risk, whereas epidemiologic studies require valid
      dietary assessment methods to examine the association of cocoa products with
      cancer risk in larger populations and to distinguish possible cancer protective
      effects of cocoa products from those due to other polyphenolic compounds.

PMID- 19838931
TI  - Nutritional factors in ovarian cancer survival.
AB  - Ovarian cancer is the leading cause of death from gynecologic malignancies in the
      United States. Because symptoms tend be nonspecific, early detection is
      difficult, and most ovarian cancers are diagnosed at an advanced stage when the
      prognosis is poor. Nonetheless, there is clinical evidence that even given the
      same tumor characteristics (histologic type, stage, and grade), some cases
      experience much better survival than others. This has led to extensive research
      on molecular prognostic factors to enable more efficient and targeted therapeutic
      regimens. However, little is known about the impact that lifestyle factors, such
      as diet or physical activity, may have in the prognosis of ovarian cancer,
      whether on disease-free survival or on the response to and complications from
      treatment. The role of obesity on ovarian cancer survival is unclear. Obesity may
      delay diagnosis, hinder optimal surgical and cytotoxic treatment, and cause
      postoperative complications. As overweight and obesity rates reach epidemic
      proportions, the impact of body mass index in the clinical management of ovarian
      cancer is increasingly significant, whereas current evidence of its impact is
      limited and inconclusive.

PMID- 19838928
TI  - Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent
      and independent pathways in human ovarian cancer cells.
AB  - Ovarian cancer is 1 of the most significant malignancies in the Western world,
      and the antiangiogenesis strategy has been postulated for prevention and
      treatment of ovarian cancers. Kaempferol is a natural flavonoid present in many
      fruits and vegetables. The antiangiogenesis potential of kaempferol and its
      underlying mechanisms were investigated in two ovarian cancer cell lines, OVCAR-3
      and A2780/CP70. Kaempferol mildly inhibits cell viability but significantly
      reduces VEGF gene expression at mRNA and protein levels in both ovarian cancer
      cell lines. In chorioallantoic membranes of chicken embryos, kaempferol
      significantly inhibits OVCAR-3-induced angiogenesis and tumor growth. HIF-1alpha,
      a regulator of VEGF, is downregulated by kaempferol treatment in both ovarian
      cancer cell lines. Kaempferol also represses AKT phosphorylation dose dependently
      at 5 to 20 muM concentrations. ESRRA is a HIF-independent VEGF regulator, and it
      is also downregulated by kaempferol in a dose-dependent manner. Overall, this
      study demonstrated that kaempferol is low in cytotoxicity but inhibits
      angiogenesis and VEGF expression in human ovarian cancer cells through both HIF
      dependent (Akt/HIF) and HIF-independent (ESRRA) pathways and deserves further
      studies for possible application in angio prevention and treatment of ovarian
      cancers.

PMID- 19838932
TI  - Natural products for chemopreventive and adjunctive therapy in oncologic disease.
AB  - Nutritional supplements or complementary and alternative medicines (CAM) are
      currently being investigated for their use in preventing, inhibiting, and
      reversing the progression of cancer. Natural agents and their derivatives such as
      vitamin A, selenium, green tea, resveratrol, aspirin, and probiotics have
      potential benefits in chemoprevention. There is also growing evidence for the use
      of natural products as adjunctive therapy alongside conventional cancer
      treatments. Nutritional supplements expenditures demonstrated greater growth than
      pharmaceuticals, with approximately 80% of cancer patients using natural
      products. Current issues with nutritional supplements use in cancer treatment
      include insufficient or conflicting evidence, poor quality control, potential
      interactions with chemotherapy, and potential efficacy in relation to changes in
      certain biomarkers, but long-term implications remain largely unresolved.
      Continued research is needed to lend credibility to these potentially valuable
      naturally driven supplements in the prevention and potentially in the treatment
      of cancer in conjunction with standard pharmaceuticals.

PMID- 19838933
TI  - Soy food consumption and risk of prostate cancer: a meta-analysis of
      observational studies.
AB  - Soybean products have been suggested to have a chemo preventive effect against
      prostate cancer. The aim of this study was to provide a comprehensive meta
      analysis on the extent of the possible association between soy-based food
      consumption and the risk of prostate cancer. Five cohort studies and 8 case
      control studies were identified using MEDLINE, EMBASE, CINAHL, Korea Medical
      Database, KoreaMed, Korean studies Information Service System, Japana Centra
      Revuo Medicina, China National Knowledge Infrastructure, and a manual search.
      Summary odds ratios (ORs) comparing high versus low categories of soybean
      consumptions were calculated on the basis of the random effect model. We analyzed
      the associations based on the different types of soybean consumptions. The
      summary ORs (95% CI) for total soy foods were 0.69 (CI = 0.57-0.84) and 0.75 (CI
      = 0.62-0.89) for nonfermented soy foods. Among individual soy foods, only tofu
      yielded a significant value of 0.73 (CI = 0.57-0.92). Consumption of soybean
      milk, miso, or natto did not significantly reduce the risk of prostate cancer.
      Genistein and daidzein were associated with a lower risk of prostate cancer. This
      systematic review suggests that soy food consumption could lower the risk of
      prostate cancer. This conclusion, however, should be interpreted with caution
      because various biases can affect the results of a meta-analysis.

PMID- 19838934
TI  - Effects of dietary fiber, fats, and meat intakes on the risk of Barrett's
      esophagus.
AB  - Animal and human models suggest associations between fat intake, fiber intake,
      and the risk of esophageal adenocarcinoma. We evaluated whether these factors may
      act early in the carcinogenic pathway as a risk factor for Barrett's esophagus, a
      potentially premalignant precursor to esophageal adenocarcinoma using a case
      control design within the Kaiser Permanente, Northern California population.
      Incident Barrett's esophagus cases (n = 296) were matched to persons with
      gastroesophageal reflux disease (GERD) (n = 308) and to population controls (n =
      309). Higher intakes of omega-3-fatty-acids [cases vs. population controls; OR =
      0.46, 95% CI = 0.22-0.97, 4th vs. 1st quartiles of intake], polyunsaturated fat,
      total fiber (OR = 0.34, 95% CI = 0.15-0.76), and fiber from fruits and vegetables
      (OR = 0.47 95% CI = 0.25-0.88) were associated with a lower risk of Barrett's
      esophagus. Higher meat intakes were associated with a lower risk of long-segment
      Barrett's esophagus (OR = 0.25, 95% CI = 0.09-0.72). In contrast, higher trans
      fat intakes were associated with increased risk (OR = 1.11; 95% CI = 1.03-1.21
      per g/day). Total fat intake, barbecued foods, and fiber intake from sources
      other than fruits and vegetables were not associated with Barrett's esophagus.
      Future studies to evaluate whether dietary interventions might influence the risk
      of Barrett's esophagus or esophageal adenocarcinoma in high risk persons are
      needed.

PMID- 19838935
TI  - Folate intake and prostate cancer risk: a case-control study.
AB  - Folate deficiency has been implicated in the carcinogenesis of several tumor
      types. The role of folate in prostate cancer remains indeterminate. We
      investigated folate as a risk factor for prostate cancer among 140 biopsy
      confirmed prostate cancer patients, 230 age-matched clinic controls, and 250
      negative prostate biopsy controls. Dietary folate intake was inversely associated
      with overall risk of prostate cancer as compared to clinic controls (P for a
      linear trend = 0.003). When stratified by disease severity, dietary folate and
      folate from natural sources were associated with reduced risk of high-grade
      cancer as compared to both clinic controls (P for a linear trend = 0.0009 and
      0.02, respectively) and biopsy negative controls (P for a linear trend = 0.03 and
      0.05, respectively). There was no interaction between alcohol consumption and
      folate intake. These analyses support an inverse association between dietary
      folate intake and prostate cancer risk and primarily risk of high-grade prostate
      cancer.

PMID- 19838936
TI  - The effects of diet on selenium concentration in serum in patients with cancer.
AB  - The aim of this study was to determine serum levels of selenium (Se) in patients
      with larynx and urinary system cancers. We also estimated the influence of
      dietary habits on Se status in examined patients. The mean content of Se in serum
      of patients with urinary system cancer (48.94 +/- 16.3 mu/l) and larynx cancer
      (51.00 +/- 18.6 mu/l) was lower than the mean content of Se in the control group
      (68.25 +/- 15.6 mircog/l; P = 0.000006 or 64.03 +/- 16.8 microg/l; P = 0.0112,
      respectively). In tissue only, the mean level of Se in patients with kidney
      cancer (75.37 +/- 40.3 mircog/l) was lower to compare with the dead body control
      group (220.68 +/- 83.6 microg/l). We have observed the correlation between the
      content of Se in serum and tissue (r = 0.297; P = 0.002). Patients with studied
      cancers have deficiency of Se in serum and kidney tissue, and it depends on the
      diet in about 30%. Frequent consumption of eggs, ham, and wine has the biggest
      influence on the content of Se in serum of patients in Poland, whereas frequent
      consumption of pulses, eggs, bacon, and lard is connected with the content of Se
      in tissue.

PMID- 19838937
TI  - Morinda citrifolia (noni) reduces cancer risk in current smokers by decreasing
      aromatic DNA adducts.
AB  - Quantitative determination of aromatic DNA adducts in peripheral blood
      lymphocytes (PBLs) of current smokers is an useful surrogate biomarker for the
      evaluation of environmental carcinogen exposure or chemopreventive intervention.
      In this study, we examined the impact of Tahitian Noni Juice (TNJ) on the
      aromatic DNA adducts of PBLs, before and after a 1-mo intervention, using (32)P
      postlabeling assay. Of 283 enrolled, 203 smokers completed the trial. Aromatic
      DNA adducts levels in all participants were significantly reduced by 44.9% (P <
      0.001) after drinking 1 to 4 oz of TNJ for 1 mo. Dose-dependent analyses of
      aromatic DNA adduct levels showed reductions of 49.7% (P < 0.001) in the 1-oz TNJ
      group and 37.6% (P < 0.001) in the 4-oz TNJ group. Gender-specific analyses
      resulted in no significant differences in the 4-oz TNJ groups. Interestingly, the
      1-oz TNJ group showed a reduction of 43.1% (P < 0.001) in females compared with
      56.1% (P < 0.001) in males. The results suggest that drinking 1 to 4 oz of TNJ
      daily may reduce the cancer risk in heavy cigarette smokers by blocking
      carcinogen-DNA binding or excising DNA adducts from genomic DNA.

PMID- 19838938
TI  - Protective effects of mastic oil from Pistacia lentiscus variation chia against
      experimental growth of lewis lung carcinoma.
AB  - Mastic oil from Pistacia lentiscus variation chia, a traditionally used dietary
      flavoring agent with medicinal properties, has been shown to exert in vitro
      antitumor activities, but no study has addressed in vivo efficacy and mechanisms
      of action. Presently, we demonstrated that treatment of immunocompetent mice with
      mastic oil (45 mg/kg body weight, intraperitoneally, 3 times a wk for
      approximately 3 wk) significantly inhibited tumor growth (56.4% +/- 5.7 maximum
      reduction in tumor volumes) without toxicity. Analysis of tumors by
      immunohistochemistry and ELISA indicated that this effect is associated with
      increased apoptosis, reduced neovascularization, and inhibition of chemokine
      expression. Likewise mastic oil reduced vascular endothelial growth factor and
      chemokine release by Lewis lung carcinoma (LLC) cells. Furthermore, mastic oil
      administration decreased small guanosine triphosphatases (GTPases) Ras, RhoA and
      nuclear factor-kappa-B-dependent reporter gene expression in vivo and in vitro,
      indicating a mechanistic link between mastic oil activities and blocking of
      relevant signaling and transcription pathways. A dose-response comparison with
      perillyl alcohol and alpha-pinene, two of its components, revealed a higher
      efficacy of mastic oil, pointing to a beneficial collective interaction among its
      ingredients. Conclusively, our results provide novel in vivo evidence of mastic
      oil inhibitory effects on tumor growth and set a rational basis for its future
      application in cancer prevention.

PMID- 19838939
TI  - Gamma tocopherol upregulates the expression of 15-S-HETE and induces growth
      arrest through a PPAR gamma-dependent mechanism in PC-3 human prostate cancer
      cells.
AB  - Chronic inflammation and dietary fat consumption correlates with an increase in
      prostate cancer. Our previous studies in the colon have demonstrated that gamma
      tocopherol treatment could upregulate the expression of peroxisome proliferator
      activated preceptors (PPAR) gamma, a nuclear receptor involved in fatty acid
      metabolism as well modulation of cell proliferation and differentiation. In this
      study, we explored the possibility that gamma-tocopherol could induce growth
      arrest in PC-3 prostate cancer cells through the regulation of fatty acid
      metabolism. Growth arrest (40%) and PPAR gamma mRNA and protein upregulation was
      achieved with gamma-tocopherol within 6 h. gamma-Tocopherol-mediated growth
      arrest was demonstrated to be PPAR gamma dependent using the agonist GW9662 and a
      PPAR gamma dominant negative vector. gamma-tocopherol was shown not to be a
      direct PPAR gamma ligand, but rather 15-S-HETE (an endogenous PPAR gamma ligand)
      was upregulated by gamma-tocopherol treatment. 15-Lipoxygenase-2, a tumor
      suppressor and the enzyme that converts arachidonic acid to 15-S-HETE, was
      upregulated at 3 h following gamma-tocopherol treatment. Expression of proteins
      downstream of the PPAR gamma pathway were examined. Cyclin D1, cyclin D3, bcl-2,
      and NFkappa B proteins were found to be downregulated following gamma-tocopherol
      treatment. These data demonstrate that the growth arrest mediated by gamma
      tocopherol follows a PPAR-gamma-dependent mechanism.

PMID- 19838941
TI  - Effect of fish oil supplementation for two generations on changes of lymphocyte
      function induced by Walker 256 cancer cachexia in rats.
AB  - Fish oil supplementation has been shown to improve the cachectic state of tumor
      bearing animals and humans. Our previous study showed that fish oil
      supplementation (1 g per kg body weight per day) for 2 generations had anticancer
      and anticachetic effects in Walker 256 tumor-bearing rats as demonstrated by
      reduced tumor growth and body weight loss and increased food intake and survival.
      In this study, the effect of fish oil supplementation for 2 generations on
      membrane integrity, proliferation capacity, and CD4/CD8 ratio of lymphocytes
      isolated from mesenteric lymph nodes, spleen, and thymus of Walker 256 tumor
      bearing animals was investigated. We also determined fish oil effect on plasma
      concentration and ex vivo production of cytokines [tumor necrosis factor-alpha
      (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6, and IL
      10]. Lymphocytes from thymus of tumor-bearing rats presented lower viability, but
      this change was abolished by fish oil supplementation. Tumor growth increased
      proliferation of lymphocytes from all lymphoid organs, and fish oil
      supplementation abolished this effect. Ex vivo production of TNF-alpha and IL-6
      was reduced in supplemented animals, but IL-4 and IL-10 secretion was stimulated
      in both nontumor and tumor-bearing rats. IL-10 and IFN-gamma plasma levels was
      also decreased in supplemented animals. These results suggest that the
      anticachetic effects of fish oil supplementation for a long period of time (2
      generations) in Walker 256 tumor-bearing rats may be associated to a decrease in
      lymphocyte function as demonstrated by reduced viability, proliferation capacity,
      and cytokine production.

PMID- 19838942
TI  - The cancer preventive seed peptide lunasin from rye is bioavailable and
      bioactive.
AB  - Lunasin is a unique 43-amino acid peptide that has been shown to be
      chemopreventive in mammalian cells and in a skin cancer mouse model against
      oncogenes and chemical carcinogens. In search for new sources of lunasin and to
      better understand the role of cereals in cancer prevention, we report here the
      properties of lunasin from rye. The stability and bioavailability were measured
      by in vitro digestibility assay using pepsin and pancreatin and feeding rats with
      lunasin-enriched rye (LER). Inhibition of histone acetyl transferase (HAT) and
      nuclear localization in mammalian cells were used to measure lunasin bioactivity.
      Lunasin is present in 15 out of 21 cultivars of rye analyzed. Lunasin present in
      rye crude protein preparation is stable to pepsin and pancreatin in in vitro
      digestion. The liver, kidney, and blood of rats fed LER show the presence of
      lunasin in Western blot. Lunasin extracted from these tissues inhibits the
      activities of HATs, confirming that the peptide is intact and bioactive. Lunasin
      purified from rye internalizes in the nuclei of mouse fibroblast cells. We
      conclude that lunasin in rye is bioavailable and bioactive and that consumption
      of rye may play an important role of cancer prevention in rye-consuming
      populations.

PMID- 19838940
TI  - Fish oil supplementation inhibits NNK-induced lung carcinogenesis in the A/J
      mouse.
AB  - High intake of fish oil with a low omega-6 (n-6)/omega-3 (n-3) polyunsaturated
      fatty acid (PUFA) ratio has been suggested to protect against many chronic
      diseases. However, the effect of different ratios of dietary n-6 and n-3 PUFA on
      lung tumorigenesis has not been investigated. In this study, we examined the
      effect of a 4 mo dietary supplementation with corn oil (with a high n-6/n-3
      ratio) and fish oil (with a low n-6/n-3 ratio) as compared with soybean oil
      (isocaloric control with the same n-6/n-3 ratio as the base diet) on tumor
      incidence and tumor prevalence in the A/J mouse model of 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis. We found that dietary
      supplementation had no effect on overall lung tumor incidence, but fish oil
      supplementation was able to decrease lung tumor prevalence by 78% and 80%
      compared to groups receiving soybean oil and corn oil supplementation,
      respectively. The inhibitory effect of fish oil on lung tumor prevalence was
      associated with increased expressions of cell cycle inhibitor p21Cip1 and
      lipoxygenase isoform 15-LOX in the lungs. These data suggest that fish oil with a
      low ratio of n-6/n-3 PUFA could be beneficial in the prevention of lung
      carcinogenesis.

PMID- 19838943
TI  - Effects of conjugated linoleic acid on myogenic and inflammatory responses in a
      human primary muscle and tumor coculture model.
AB  - The antiproliferative and anti-inflammatory properties of conjugated linoleic
      acid (CLA) make it a potentially novel treatment in chronic inflammatory muscle
      wasting disease, particularly cancer cachexia. Human primary muscle cells were
      grown in coculture with MIA PaCa-2 pancreatic tumor cells and exposed to varying
      concentrations of c9,t11 and t10,c12 CLA. Expression of myogenic (Myf5, MyoD,
      myogenin, and myostatin) and inflammatory genes (CCL-2, COX-2, IL-8, and TNF
      alpha) were measured by real-time PCR. The t10,c12 CLA isomer, but not the c9,t11
      isomer, significantly decreased MIA PaCa-2 proliferation by between 15% and 19%.
      There was a marked decrease in muscle MyoD and myogenin expression (78% and 62%,
      respectively), but no change in either Myf5 or myostatin, in myotubes grown in
      coculture with MIA PaCa-2 cells. CLA had limited influence on these responses. A
      similar pattern of myogenic gene expression changes was observed in myotubes
      treated with TNF-alpha alone. Several-fold significant increases in CCL-2, COX-2,
      IL-8, and TNF-alpha expression in myotubes were observed with MIA PaCa-2
      coculture. The c9,t11 CLA isomer significantly decreased basal expression of TNF
      alpha in myotubes and could ameliorate its tumor-induced rise. The study provides
      insight into the anti-inflammatory and antiproliferative actions of CLA and its
      application as a therapeutic agent in inflammatory disease states.

PMID- 19838944
TI  - Anticancer properties of Ganoderma lucidum methanol extracts in vitro and in
      vivo.
AB  - Anticancer activities of various extracts of the medicinal mushroom, Ganoderma
      lucidum, have been widely demonstrated and are mainly associated with the
      presence of different bioactive polysaccharides and triterpenoids. We have
      evaluated and compared in vitro and in vivo the antitumor effects of two
      preparations from Ganoderma lucidum: a methanol extract containing total
      terpenoids (GLme) and a purified methanol extract containing mainly acidic
      terpenoids (GLpme). Both extracts inhibited tumor growth of B16 mouse melanoma
      cells inoculated subcutaneously into syngeneic C57BL/6 mice and reduced viability
      of B16 cells in vitro, whereby GLme exhibited stronger effect. Furthermore,
      anticancer activity of GLme was demonstrated for the first time against two other
      rodent tumor cell lines, L929-mouse fibrosarcoma and C6-rat astrocytoma. The
      mechanism of antitumor activity of GLme comprised inhibition of cell
      proliferation and induction of caspase-dependent apoptotic cell death mediated by
      upregulated p53 and inhibited Bcl-2 expression. Moreover, the antitumor effect of
      the GLme was associated with intensified production of reactive oxygen species,
      whereas their neutralization by the antioxidant, N-acetyl cysteine, resulted in
      partial recovery of cell viability. Thus, our results suggest that GLme might be
      a good candidate for treatment of diverse forms of cancers.

PMID- 19838945
TI  - Soy consumption and histopathologic markers in breast tissue using tissue
      microarrays.
AB  - This study examined the relation of soy intake with hormonal and proliferation
      markers in benign and malignant breast tissue using tissue microarrays (TMAs).
      TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer
      cases were constructed. Soy intake in early life and in adulthood was assessed by
      questionnaire. The TMAs were stained for estrogen receptor (ER) alpha, ERbeta,
      progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu),
      proliferating cell nuclear antigen (PCNA), and Ki-67 using standard
      immunohistochemical methods. Logistic regression was applied for statistical
      analysis. A higher percentage of women showed positive marker expression in
      malignant than in benign tissue. With one exception, HER2/neu, no significant
      associations between soy intake and pathologic markers were observed. Early life
      soy intake was associated with lower HER2/neu and PCNA staining of malignant
      tissue. In benign tissue, early life soy intake showed higher ER and PR
      expression, but no difference in proliferation markers. The results of this
      investigation provide some assurance that soy intake does not adversely affect
      markers of proliferation. TMAs were shown to be a useful tool for epidemiologic
      research.

PMID- 19838946
TI  - Effects of quercetin and catechin on hepatic glutathione-S transferase (GST),
      NAD(P)H quinone oxidoreductase 1 (NQO1), and antioxidant enzyme activity levels
      in rats.
AB  - Cell culture data indicate that quercetin and catechin may affect the activity of
      phase II and antioxidant enzymes. However, little is known about the impact of
      dietary flavonoids in vivo. Therefore, the present study aimed to investigate the
      in vivo effects of the flavonoids quercetin and catechin on mRNA and activity
      levels of phase II enzymes glutathione-S transferase (GST) and NAD(P)H quinone
      oxidoreductase-1 (NQO1) in rat liver. Furthermore, the activity of the hepatic
      antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide
      dismutase (SOD) was determined. Feeding male Wistar rats (3 x 6 animals) over 3
      wk with semisynthetic diets enriched with quercetin and catechin (2 g/kg diet)
      did not affect liver enzyme activity of CAT, GPx, and SOD as well lipid
      peroxidation and glutathione levels. Dietary quercetin significantly decreased
      activity of hepatic GST (24%), whereas dietary catechin significantly decreased
      NQO1 activity (26%) compared to controls. Changes in GST and NQO1 activity were
      partly reflected on mRNA levels. Current data indicate that dietary flavonoids
      have little effects on liver oxidant/antioxidant status but do significantly
      affect the phase II enzymes GST and NQO1 in rat liver. This in turn may affect
      the ability of the organism to detoxify endogenous and exogenous xenobiotics.

PMID- 19838947
TI  - 2'-Benzoyloxycinnamaldehyde inhibits tumor growth in H-ras12V transgenic mice via
      downregulation of metallothionein.
AB  - Cinnamaldehydes have been reported to induce apoptosis in human carcinomas
      through the generation of reactive oxygen species (ROS). 2'
      benzoyloxycinnamaldehyde (BCA) has been reported to inhibit tumor formation in H
      ras12V transgenic mice. To see the antitumor effects of BCA, BCA was
      administrated intraperitoneally (50 mg/kg) to H-ras12V transgenic mice for 3 wk,
      and it was found that the hepatic tumor volume and the total number of tumors
      were decreased in BCA-treated mice as compared to control H-ras12V transgenic
      mice. To identify possible target genes responsible for BCA antitumor effects in
      H-ras12V transgenic mice, cDNA microarray analyses were performed comparing gene
      expression between BCA treated and control transgenic mice. We found that 42
      genes were downregulated, and 40 genes were upregulated in the BCA-treated
      transgenic mice. The downregulated genes included several genes involved in ROS
      regulation and immune response (aconitase, metallothionein-1, metallothionein-2,
      and purine nucleoside phosphorylase). The expression of ROS-related genes,
      metallothionein 1 and metallothionein 2, was decreased more than twofold with BCA
      treatment (P < 0.001). It was confirmed by RT-PCR and immunohistochemical
      analyses. The inhibition of tumor formation and growth in H-ras12V transgenic
      mice by BCA was mediated through inhibition of the expression of the ROS
      scavengers metallothionein 1 and metallothionein 2.

PMID- 19838948
TI  - Quercetin induces oxidative stress and potentiates the apoptotic action of 2
      methoxyestradiol in human hepatoma cells.
AB  - Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia.
      This study evaluated the growth inhibition effect of quercetin and 2
      methoxyestradiol in vitro in human HCC cell lines. Combination treatment enhanced
      the cytotoxic effect in HA22T/VGH and HepG2 cell lines as compared with quercetin
      or 2-methoxyestradiol alone. The cell population of sub-G0/G1 phase and the level
      of annexin V binding were increased synergistically after combination treatment
      with quercetin and 2-methoxyestradiol in both cell lines. Moreover, quercetin
      combined with 2-methoxyestradiol increased superoxide levels, mitochondrial
      superoxide dismutase (MnSOD) in mRNA, protein levels, and SOD activity. Finally,
      we also found the mitochondrial membrane potential was decreased after
      combination treatment. The changes of reactive oxygen species and mitochondrial
      disruption were likely to be involved in the mechanism for the synergistic
      cytotoxicity effects of combination treatment in human hepatoma cells. These
      results provided a basis for further study of the potential usage of quercetin
      combination with hormonal agents for the treatment of human hepatoma.

PMID- 19838949
TI  - Stearate preferentially induces apoptosis in human breast cancer cells.
AB  - Stearic acid (stearate) is an 18-carbon saturated fatty acid that has been shown
      to inhibit invasion and proliferation and induce apoptosis in various human cell
      types. The specificity of stearate-induced apoptosis for cancerous versus
      noncancerous breast cells has not been examined, and the mechanism underlying
      stearate-induced apoptosis is unknown. Morphological analysis, cell viability,
      and caspase-3 activity assays demonstrated that stearate activated apoptosis
      preferentially in cancerous breast cells in a time- and dose-dependent manner.
      Inhibition of de novo diacylgycerol synthesis or protein kinase C (PKC) blocked
      stearate-induced caspase-3 activity, indicating the involvement of a novel or
      classical PKC isozyme. To our knowledge this is the first study showing that
      stearate induces apoptosis preferentially in breast cancer cells and implicates
      protein kinase C in the signaling cascade. These results raise the possibility of
      dietary stearate having a beneficial role in the prevention or treatment of
      breast cancer.

PMID- 19838950
TI  - Is Hsp27 a marker of myocardial ischaemia?
AB  - BACKGROUND: Heat shock protein (Hsp) 27 expression in cardiomyocytes increases in
      response to ischaemia. The extracellular release of Hsp27 from cardiomyocytes is
      proportional to its intracellular levels. AIM: To assess the influence of
      significant coronary artery disease (CAD), which by definition results in chronic
      myocardial ischaemia, on blood serum levels of Hsp27. METHODS: Blood serum levels
      of Hsp27 in 62 patients with at least 50% lumen diameter narrowing in at least
      one main epicardial coronary artery on angiography and in 21 controls with normal
      coronaries were measured. RESULTS: Patients with CAD tended to have higher serum
      level of Hsp27 than controls [0.463 (0.158-0.809) vs. 0.184 (0.099-0.337) ng/ml,
      p = 0.084]. Serum Hsp27 level in patients with CAD affecting more than a single
      vessel was significantly increased [0.529 (0.192-1.004) ng/ml] compared with
      controls (p = 0.035) and with one artery narrowed [0.276 (0.087-0.549) ng/ml, p =
      0.041]. No correlation between Hsp27 serum levels and severity of coronary
      narrowings assessed by Gensini score was found (r = 0.21, p = 0.11). CONCLUSIONS:
      Serum level of Hsp27 seems to be a potential marker of myocardial ischaemia
      caused by advanced 2- or 3-vessel CAD.

PMID- 19838951
TI  - Desmin expression in human cardiomyocytes and selected clinical and
      echocardiographic parameters in patients with chronic heart failure.
AB  - BACKGROUND: Desmin, one of the basic muscular-specific structural proteins, is
      believed to play an important role in the progression of heart failure (HF). The
      function of desmin in cardiomyocytes is still unclear. Mechanical, structural and
      regulatory functions are postulated. Regulatory function of desmin seems the most
      interesting. Desmin might be involved in the regulation of gene expression,
      myofibrillogenesis and intercellular signalling, and be responsible for shape and
      tension of the cell membrane and other organelles. Abnormal accumulation of
      desmin may disturb the function of myofibrils, lead to unusual tension of
      sarcolemma and atypical distribution of organelles (nucleus), and impair intra-
      and intercellular communication. AIM: Evaluation of desmin expression in
      specimens derived from right ventricular myocardium during endomyocardial biopsy
      (EMB). METHODS: The study population consisted of 135 patients (86.7% males, mean
      age 49.4 +/- 14.1 years) presenting with clinical symptoms of HF and LVEF < 45%.
      During EMB 3-4 samples were taken from the right ventricular myocardium. The
      immunohistochemical studies of the endomyocardial specimens included
      immunostaining with desmin-specific antibodies. The study population was divided
      into three groups: I - 48 patients with normal expression of desmin, II - 54
      patients with increased expression and accumulation of desmin and III - 33
      patients with low expression of desmin in cardiomyocytes. RESULTS: The LVEF was
      significantly higher in group I than in groups II and III. The LV diameter was
      significantly lower in group I than in groups II and III. Functional status
      according to NYHA class was the worst in group I compared to group II and III.
      These differences were statistically significant. CONCLUSION: Evaluation of
      desmin distribution in specimens derived from the right ventricular myocardium
      may be useful as an objective tool in the assessment of left ventricle status.

PMID- 19838952
TI  - The effect of an evening dose of a long-acting beta-blocker on the autonomic tone
      in patients with congestive heart failure.
AB  - BACKGROUND: Heart rate variability (HRV) indices are accepted markers of cardiac
      autonomic activity and have been used as indicators of beta-blockade effects in
      congestive heart failure (CHF) patients. In view of the high frequency of sudden
      cardiac death in the morning, there is a question whether the evening beta
      blocker administration would be more efficient than a morning dose. AIM: To
      compare HRV indices after morning or evening long-acting beta-blocker
      administration. METHODS: The study group consisted of 52 CHF patients (NYHA class
      II/III) in sinus rhythm. Time domain (TD) and frequency domain (FD) HRV analyses
      were performed for daytime, nighttime and a 24-hour period: first after the
      morning bisoprolol administration, and then after the same evening dose. RESULTS:
      After the evening dose the mean heart rate was significantly lower (p = 0.01),
      nighttime normal R-R intervals were significantly prolonged (p = 0.008) and the
      low frequency (LF)/high frequency (HF) ratio was significantly lower for: 24 h (p
      = 0.0002); daytime (p = 0.003) and nighttime (p = 0.008) with higher HF values in
      the 24-hour period (p = 0.0007) and in the daytime interval (p = 0.006).
      CONCLUSION: An evening dose of a beta-blocker is more effective than a morning
      dose in reversing adverse changes in the autonomic nervous system activity in CHF
      patients.

PMID- 19838953
TI  - Predictors of the atrial fibrillation occurrence in patients with Wolff-Parkinson
      White syndrome.
AB  - BACKGROUND: Atrial fibrillation (AF) in WPW syndrome occurs earlier and is more
      common than in the general population. AIM: To evaluate the predisposing factors
      for the first episode of AF in patients with WPW. METHODS: We analysed data on
      930 patients (510 males, 420 females) with WPW treated in our centre during 1988
      2007. AF was diagnosed in 236 patients (25% - 161 males, 75 females, aged 36 +/-
      15 years). The AF group was divided into two subgroups - patients with AF and
      atrio-ventricular reentrant tachycardia (AVRT), and patients with AF only. The
      analysis included subjects' age and gender, the presence of AVRT, the number and
      properties of accessory pathways, left ventricular ejection fraction (LVEF) and
      concomitant cardiovascular diseases. RESULTS: The groups did not differ in terms
      of concomitant diseases and LVEF. In the whole group of patients with AF,
      arrhythmia occurred earlier in men than in women (34 +/- 14 vs. 40 +/- 15 years
      of age, p = 0.013). In the subgroup with AF and AVRT, AF was documented earlier
      compared to patients with AF only (34 +/- 15 vs. 41 +/- 15 years of age, p =
      0.0072). AVRT was more common in patients with AF compared to those without AF
      (69 vs. 53%, p < 0.001). In the whole group of 930 patients, AF was observed more
      often in patients with overt pre-excitation compared to concealed WPW (29 vs.
      12%, p < 0.001). CONCLUSIONS: In patients with WPW syndrome, AF occurs earlier in
      patients with AVRT compared to patients with AF and without documented AVRT,
      earlier in men compared to women, and is more common in patients with overt WPW.

PMID- 19838954
TI  - The association between Chlamydia pneumoniae DNA in arherosclerotic plaque and
      major risk factors in patients undergoing coronary artery bypass grafting.
AB  - BACKGROUND AND AIM: This study was conducted to investigate the prevalence of
      Chlamydia pneumoniae pathogen inside the atherosclerotic plaque of patients
      undergoing CABG by using PCR assay and to determine whether there is any
      association between the presence of bacteria in atherosclerotic lesions and
      classical coronary risk factors. METHODS: In a cross-sectional study, 102
      patients (20 to 79 years old; 73.5% male) undergoing CABG were evaluated in terms
      of major coronary risk factors and the presence of Chlamydia pneumoniae. RESULTS:
      Chlamydia pneumoniae was found in 23.4% of coronary plaque specimens. Of these,
      two patients had no risk factor and the rest of the patients had 1 to 3 risk
      factors. Patients with positive PCR were more likely to have
      hypercholesterolaemia (p = 0.009) and low HDL levels (p = 0.000) in comparison
      with the PCR-negative group. There were no statistical differences for other risk
      factors. CONCLUSION: Our results imply the synergic contribution of Chlamydia
      pneumoniae DNA and known dyslipidaemia to the development of atherosclerotic
      lesions in patients undergoing CABG.

PMID- 19838955
TI  - Pulmonary hypertension - intra- and early postoperative management in patients
      undergoing lung transplantation.
AB  - BACKGROUND: Single lung transplantation, bilateral lung transplantation and
      combined heart-lung transplantation are the procedures currently being performed
      in patients with arterial pulmonary hypertension and pulmonary hypertension as a
      result of end-stage lung disease. In patients with severe pulmonary hypertension,
      regardless of its aetiology, general anaesthesia and mechanical ventilation could
      precipitate the onset of cardiac failure and the necessity of extracorporeal
      circulation employment. AIM: To assess the clinical and prognostic value of the
      pulmonary artery pressure (PAP) measured during the intra- and early
      postoperative period in patients undergoing lung transplantation. METHODS: We
      analysed 20 patients undergoing lung transplantation in the Silesian Centre for
      Heart Disease in Zabrze, of whom 13 suffered from pulmonary hypertension before
      the operation. The PAP was measured using Swan-Ganz catheters. RESULTS: Pulmonary
      artery pressure markedly decreased after transplantation (systolic, diastolic and
      mean PAP values were 31/19/23 mmHg, respectively) but in 3 recipients the mean
      PAP exceeded 25 mmHg (45/23/30 mmHg). In all 3 cases a cardiopulmonary bypass was
      required and single-lung transplantation was performed. Pulmonary hypertension
      immediately after the operation was the potential marker of lung dysfunction
      (pulmonary oedema, ischaemia-reperfusion injury, infection) - all 3 patients with
      increased PAP developed complications. CONCLUSIONS: Lung transplantation is
      associated with a significant reduction in pulmonary artery pressures immediately
      after graft implantation. The persistence of pulmonary hypertension in the early
      postoperative period suggests temporal allograft dysfunction and affects the post
      operative outcome.

PMID- 19838956
TI  - Significant stenosis of proximal left subclavian artery presenting with absence
      of left radial pulse and recurrent angina after coronary artery bypass grafting.
AB  - Stenosis of the subclavian artery, before the left internal mammary artery
      branch, is an important problem for patients who have undergone coronary artery
      bypass grafting, with an incidence rate of 0.5-1.1%. In this paper, a case of
      left subclavian artery stenosis, which developed after coronary artery bypass
      surgery and led to recurrent anginal attacks in the patient, is presented.

PMID- 19838957
TI  - [Venous thromboembolism in a patient with noninvasive thymoma and a history of
      pemphigus].
AB  - A case of a 69-year-old man, admitted due to an acute episode of venous
      thromboembolism (VTE) is described. He had a 3-year history of 'asymptomatic'
      (revealed on routine chest X-ray, but undiagnosed) tumor of anterior mediastinum,
      and a 8-year history of pemphigus vulgaris treated mainly with steroids. Three
      months following VTE episode he underwent tumor resection and histopathologic
      evaluation showed noninvasive, type AB thymoma. Gradual pemphigus remission
      started some weeks later. We analyse the relationship between thymoma, pemphigus
      and VTE, and emphasize the usefulness of echocardiographic thymoma imaging as a
      method complementary to computed tomography/magnetic resonance.

PMID- 19838958
TI  - [Infective endocarditis of both atrioventricular valves in a young man with
      atrioventricular canal defect - a case report].
AB  - We report a case of a 33-year-old man with infective endocarditis of both
      atrioventricular valves coexisting with a congenital heart defect:
      atrioventricular canal defect. Transthoracic and transesopageal echocardiography
      showed complete atrioventricular canal defect and vegetations affecting both the
      normal mitral and tricuspid valves. The patient received a combined antibiotic
      therapy and was qualified for cardiosurgical correction.

PMID- 19838959
TI  - [Massive pulmonary embolism without echocardiographic features of right
      ventricular overload].
AB  - A case of 70-year-old patient with massive pulmonary embolism confirmed in CT,
      but without changes in right ventricle size and function in echocardiography is
      presented. This case is consistent with literature data that echocardiography has
      relatively low sensitivity in the diagnosis of acute pulmonary embolism.

PMID- 19838960
TI  - [The role of genetic polymorphisms of cytochrome P450 in drug metabolism used in
      the treatment of cardiovascular diseases].

PMID- 19838961
TI  - [Autosomal dominant hypercholesterolemia - underrecognised diagnostic and
      clinical problem].

PMID- 19838962
TI  - [Pulmonary embolism in the XXth and XXIst century - a comparison of the European
      Cardiology Society guidelines from 2000 and 2008].

PMID- 19838963
TI  - [Supernormal excitability and conduction in the human heart -
      electrocardiographic myth or reality?].
AB  - Three cases of possible supernormal conduction and excitability are described.
      Case one: subthreshold stimulation with ventricular capture occurring only at the
      end of the T wave. Case two: advanced atrioventricular block with conduction
      present only when P waves fell at the downsloping part of the T wave of
      ventricular escape beats. Case three: 2 : 1 atrioventricular block at atrial
      pacing rate of 115 bpm with improvement of conduction during higher pacing rates
      (3 : 2 block at 130 bpm and above; with negligible PR prolongation). Possible
      alternative mechanisms: gap phenomenon, ventriculophasic modulation of vagal
      discharge, ventriculophasic pacing lead movement and concealed 2 : 1
      atrioventricular block due to superimposed ventricular escape rhythm, are
      discussed and considered either impossible or unlikely.

PMID- 19838964
TI  - [Isolated left ventricular non-compaction - various clinical presentations].
AB  - The isolated left ventricular non-compaction (LVNC) is an increasingly commonly
      diagnosed myocardial disorder resulting from a defective morphogenesis of the
      endomyocardium. This is associated with high rates of thromboembolism, cardiac
      failure, and cardiac arrhythmia. The report describes 3 cases of LVNC, presenting
      with different clinical pictures.

PMID- 19838965
TI  - Stent dislodgement in left anterior descending coronary artery and successful
      deployment with two parallel wires and a small balloon.
AB  - Coronary artery stent dislodgement during angioplasty is a rare complication.
      Stent dislodgement was more frequent in the past when stents were manually
      crimped onto the balloon. Newer and improved balloon-mounted stents with better
      radio-opacity have reduced the incidence of stent dislodgement but do not
      completely eliminate it. We report a case of balloon-mounted stent dislodgement
      in the proximal left anterior descending (LAD) coronary artery prior to
      deployment. This patient however was successfully treated with re-wiring of the
      artery with two parallel wires and the stent's reposition prior to deployment
      with the help of a small balloon.

PMID- 19838966
TI  - [Thoracoscopic Ex-Maze III procedure and radiofrequency catheter ablation - a
      hybrid therapy for permanent atrial fibrillation. A case report].
AB  - We desribe a case of a 57-year-old patient with persistent longstanding atrial
      fibrillation (AF) in whom paracardioscopic Ex-Maze III procedure converted AF to
      typical counterclockwise atrial flutter. Subsequent catheter RF ablation of cavo
      tricuspid isthmus restored sinus rhythm. We propose that the hybrid therapy
      including thoracoscopic maze procedure and catheter RF ablation of flutter
      isthmus might be effective in some patients with permanent AF. To the best of our
      knowledge this approach was never published before. Lelako.

PMID- 19838967
TI  - [Minimally invasive, hybrid ablation in a patient with persistent atrial
      fibrillation - early experience].

PMID- 19838968
TI  - Endoscopic treatment of intraventricular cerebrospinal fluid cysts: 10
      consecutive cases.
AB  - INTRODUCTION: The use of the endoscope for lesions of the central nervous system
      has been progressively widened in the past decades. Among these lesions, the
      intraventricular cyst is one of the most attractive targets for this less
      invasive procedure. METHODS: Between 2003 and 2007, ten consecutive patients with
      IVC underwent endoscopic surgery in our department. The location of the cyst was
      the lateral ventricle in nine, the lateral and third ventricles in one. The cyst
      was resected or fenestrated according to the degree of adhesion of the cyst wall
      with the ventricular wall. The follow-up ranged from 6 months to 54 months (mean:
      22.5 months). RESULTS: The cyst was totally removed in three, subtotally removed
      in one, and fenestrated in six cases. Except for transient fever, there was no
      post-operative morbidity. During follow-up, all patients were doing well.
      CONCLUSION: The endoscopic technique is a good treatment option with the
      advantage of minimal invasiveness and less complications. The extension of the
      cyst and whether the hemisphere involved is dominant or not, determines the ideal
      endoscopic trajectory. The long-term efficacy of the endoscopic technique in
      treatment of IVC needs further evaluation.

PMID- 19838969
TI  - The minimally invasive supraorbital subfrontal key-hole approach for surgical
      treatment of temporomesial lesions of the dominant hemisphere.
AB  - INTRODUCTION: Surgery in the temporomesial region is generally performed using a
      subtemporal, transtemporal, or pterional-transsylvian approach. However, these
      approaches may lead to approach-related trauma of the temporal lobe and
      frontotemporal operculum with subsequent postoperative neurological deficits.
      Iatrogenic traumatisation is especially significant if surgery is performed in
      the dominant hemisphere. METHODS: During a five-year period between January 2003
      and December 2007, we have approached the temporomesial region in 21 cases via
      the supraorbital approach. In 15 cases, the lesion was located within the
      dominant hemisphere, all lesions had space-occupying effects. In all cases,
      meticulous approach planning was performed, demonstrating a close proximity of
      the lesion to the pial surface on the upper anterior mesial aspect of the
      temporal lobe. An extension within the parahippocampal gyrus or with deep
      temporobasal tumor growth below the sphenoid wing were considered as exclusion
      criteria for using the supraorbital approach. RESULTS: In all cases surgery was
      performed without intraoperative complications. Pathological investigation showed
      7 low-grade astrocytomas, 4 high-grade astrocytomas, 2 gangliogliomas and 2
      cavernomas. Early postoperative MRI scans confirmed a complete removal of the
      lesion in 14 cases. In one case of a subtotal resection, the residual tumor was
      removed through a posterior subtemporal approach. The postoperative neurological
      examination was unchanged in 14 cases. In one case a transient hemiparesis was
      observed. In patients with dominant-sided lesions no speech or mental deficits
      were present. CONCLUSION: In selected cases, the minimally invasive supraorbital
      craniotomy offers excellent surgical efficiency in the temporomesial region with
      no approach-related morbidity compared to a standard transtemporal or pterional
      transsylvian approach.

PMID- 19838970
TI  - Histological demonstration of healing in experimental aneurysms.
AB  - INTRODUCTION: Recanalisation of aneurysms after interventional therapy is still
      an unsolved problem. The aim of this study is to demonstrate the angiographic and
      histological evidence of healing after endovascular embolisation of experimental
      aneurysms. METHODS: We evaluated the healing reaction in experimental aneurysms
      treated with HydroCoils and platinum coils. After microsurgical construction of
      aneurysms in 24 rabbits, embolisation was performed. Four animals were sacrificed
      immediately after embolisation and 5 after 1 month, 3 months and 6 months,
      respectively, the remaining served as control group. Serial plastic-embedded
      ground sections of the parent arteries-aneurysm complexes were evaluated by light
      microscopy. RESULTS: Thrombus organisation in the aneurysms resulted in
      fibrovascular tissue formation between bare platinum and HydroCoils from the
      walls of the aneurysms towards the centre of the sac over time. In the clefts
      between HydroCoils only thin strands of granulation tissue were observed. From
      one month on, there was a neointimal layer covering the coil mass at the aneurysm
      orifice. CONCLUSION: Progressive occlusion by the expanding hydrogel polymers on
      the coils seemed to result in a durable healing reaction in the aneurismal sac in
      a short-term follow-up period.

PMID- 19838971
TI  - Minimally invasive awake craniotomy using Steiner-Lindquist stereotactic laser
      guidance.
AB  - INTRODUCTION: Awake craniotomy permits the continuous assessment of
      intraoperative neurological functions. In addition, stereotactic laser guidance
      aids in performing minimally invasive procedures related to the radical resection
      of lesions located in eloquent and non-eloquent brain regions. METHODS: Between
      May 2000 and October 2006, 117 consecutive patients with various intracranial
      tumoral lesions underwent 141 resection procedures. The eloquent areas were
      determined with the aid of anatomic landmarks and/or functional MRI (fMRI)
      examinations. The resection of the lesions was performed under continuous
      neurological examination. In all cases, postoperative MRI was performed within 24
      72 h. RESULTS: Seventy-seven males and 40 females were included in this study.
      The mean age of the patients was 52.0+/-12.6 years. Most of the lesions were
      located within the parietal lobe. Of the lesions, 33 (23.4%) were located within
      the cortex, whereas 108 (76.5%) were subcortical. The most common pathologies
      were metastasis (70 cases) and glioblastome multiforme (27 cases). In 20 (14.2%)
      of the patients, fMRI was performed preoperatively. Of 21 patients with multiple
      lesions, 18 underwent 2 craniotomies and 3 underwent 3 craniotomies. The mean
      operation time was 72+/-0.3 min, and the mean hospital stay was 3.26+/-1.82 d.
      The average lesion size was 11.92+/-15.26 cm(3). In 7 cases (4.9%), the surgery
      caused either new neurological deficits or a worsening of the existing deficits;
      these deficits were permanent in 2 (1.4%) cases. One patient (0.7%) died due to
      the development of postoperative intracerebral hemorrhage. CONCLUSIONS: Awake
      craniotomy with the aid of stereotactic laser guidance is a safe procedure that
      assists in performing minimally invasive resection of lesions in eloquent and non
      eloquent brain regions. Although direct intraoperative stimulation was not
      performed, detection of the functioning areas of the brain with fMRI decreased
      additional postoperative neurological deficits. Overall, this method decreased
      the operation time and hospital stay.

PMID- 19838972
TI  - Prospective comparative study of lumbar sequestrectomy and microdiscectomy.
AB  - INTRODUCTION: During microsurgical disc operation, usually a sequestrectomy and a
      nucleotomy are performed. Whether a nucleotomy is necessary in any case is
      disputed. The aim of this study is to examine this question on the basis of
      clinical results and to compare rates of recurrence between the two groups.
      METHODS: A prospective analysis was performed in 100 patients with sequestrectomy
      and the first 100 consecutive patients with microdiscectomy out of a cohort of
      1,245 patients, who were operated by six surgeons between 2003 and 2006. The
      study is designed with special emphasis on the actual pain status, the functional
      capacity and recurrence. RESULTS: Despite more comorbidities the hospitalization
      was significantly shorter in the sequestrectomy-treated group. This group
      revealed more favourable results on pain scales (VAS visual analogue scale). The
      percentage of back pain in the discectomy-treated group was significantly higher.
      This went along with a significantly higher consumption of painkillers. At follow
      up (34 months after surgery on average), there were no differences in the
      activities of daily live, measured by patient's questionnaires (ODI Oswestry low
      back pain disability questionnaire). Complete questionnaires were available for
      46 of the sequestrectomy patients, and for 45 of the discectomy patients. Early
      reherniation occurred in two patients after discectomy and late reherniation in
      one patient after sequestrectomy. CONCLUSIONS: Sequestrectomy alone is a safe
      operative modality. Sequestrectomy does not seem to entail a higher rate of
      recurrences compared with microdiscectomy and the results are as favourable as or
      better than results after discectomy.

PMID- 19838973
TI  - Endoscopic radial artery harvesting for U-clip EC-IC bypass in the treatment of a
      giant petrous internal carotid artery aneurysm: technical case report.
AB  - INTRODUCTION: High-flow extracranial-intracranial (EC-IC) bypass and aneurysm
      trapping constitutes a well-known surgical solution for internal carotid artery
      (ICA) aneurysms that are not amenable to clip ligation or endovascular therapy.
      The advantages of the radial artery (RA) as a conduit for myocardial
      revascularization have become widely accepted, with a better patency rate than
      that of the saphenous vein. CASE REPORT: A 66-year-old woman was found to harbour
      a right giant, partially thrombosed aneurysm of the intrapetrous segment of the
      internal carotid artery. Endoscopic harvesting of the RA was achieved combining a
      resterilizable retractor and a vessel sealing system. After neck dissection, the
      main trunk of the middle cerebral artery (MCA), its branches, and part of the
      aneurysm were isolated through a right fronto-orbito-zygomatic craniotomy. The
      external carotid artery, distal to the origin of the facial artery, was chosen in
      the neck for an end-to-end microanastomosis. The temporal branch of the MCA was
      selected for an end-to-side microanastomosis with the radial graft using ten U
      clips. The total temporary occlusion time was 13 min. The post-operative course
      was uneventful. CONCLUSION: Endoscopic technique provides improved patient
      satisfaction, especially in terms of length of the surgical incision, when
      compared to the conventional approach. Combined with the innovative use of U
      clips, this case illustrates how new technologies can simplify ECA-ICA bypass
      surgery while yielding a better cosmetic and functional outcome.

PMID- 19838974
TI  - Endoscopic transsphenoidal surgery for isolated fibrous dysplasia of the clivus.
AB  - INTRODUCTION: Fibrous dysplasia is a non-neoplastic disorder of bone, related to
      abnormal proliferation of fibro-blasts. CASE REPORT: We report a 41-year-old
      female who presented with hyperprolactinaemia and an incidental clival lesion on
      MR scan. This was sub-totally resected via an endoscopic transsphenoidal approach
      and fibrous dysplasia was confirmed histologically. Her postoperative re-covery
      was un-eventful and at 8 months follow-up, she remains well, other than for the
      intermittent headaches and with no pituitary hormone deficiencies. CONCLUSION:
      The present case highlights the need to consider fibrous dysplasia in the
      differential diagnosis of isolated clival lesions.

PMID- 19838975
TI  - Endovascular treatment for bow hunter's syndrome: case report.
AB  - INTRODUCTION: Bow hunter's syndrome is a unique clinical entity caused by
      mechanical occlusion of the vertebral artery on head rotation. Although it is
      usually treated by direct surgical intervention, we report successful treatment
      using endovascular stent placement for contralateral vertebral artery stenosis.
      CASE DESCRIPTION: A 56-year-old man presented with repeated vertigo and loss of
      consciousness caused by turning his head to the left. Right vertebral angiogram
      showed no abnormalities with the head in the neutral position. However, with the
      head rotated 60 degrees to the left, the right vertebral artery was completely
      occluded at the C1-2 level. A three-dimensional angiogram with bone window
      clearly demonstrated vertebral artery compression at the C1-2 level by the bony
      structure. The left subclavian angiogram revealed severe stenosis at the origin
      of the left vertebral artery. Left vertebral artery angioplasty followed by stent
      placement was successfully performed under local anesthesia. The patient showed
      an uneventful postoperative course and his preoperative symptoms disappeared. At
      6 months postoperatively, a left subclavian angiogram showed good patency of the
      stented left vertebral artery and the patient showed no recurrent symptoms.
      CONCLUSION: Vertebral artery stenting is a useful and less invasive option in the
      treatment of bow hunter's syndrome in the setting of contralateral vertebral
      artery stenosis.

PMID- 19838976
TI  - Neuronavigation in the minimally invasive presacral approach for lumbosacral
      fusion.
AB  - INTRODUCTION: Intraoperative 3D navigation (3D NAV) is gaining importance in
      spinal surgery, especially with the advancement of minimally invasive techniques
      in this field. We hypothesized that 3D NAV may be of benefit in the recently
      described minimally invasive presacral approach for L4-S1 fusion (AxiaLIF).
      METHODS: Five patients with refractory low back pain and L5-S1 degenerative
      disease underwent 3D NAV-assisted placement of a presacral L5-S1 screw.
      Additionally, a patient recently underwent a two-level AxiaLIF procedure (L4-S1)
      which was also performed with 3D NAV. Navigation was performed by acquiring
      intraoperative images via isocentric fluoroscopy and utilizing frameless
      stereotaxy. Accuracy of 3D NAV was confirmed by overlapping intraoperative
      images, navigation screenshots, and postoperative CT scans. Outcome was
      determined by pre- and postoperative VAS (back and leg pain) and ODI. RESULTS:
      Operative results were reviewed for all six patients and clinical outcomes were
      retrospectively reviewed for the five L5-S1 procedure patients. Postoperative
      imaging demonstrated accurate screw placement in comparison to intraoperative C
      arm imaging and navigation imaging in all patients. No perioperative
      complications were encountered. In the five one-level patients, mean VAS (for
      back and leg pain) and ODI improved significantly at most recent follow-up.
      CONCLUSION: The minimally invasive presacral approach to L4-L5-S1 fusion can be
      performed safely and accurately with intraoperative 3D NAV. This is especially
      the case in two-level AxiaLIF procedures, where computer guidance can provide
      better planning possibilities for optimal screw trajectory.

PMID- 19838977
TI  - Technique for shaping microcatheter tips in coil embolization of paraclinoid
      aneurysms using full-scale volume rendering images of 3D rotational angiography.
AB  - INTRODUCTION: In coil embolization of paraclinoid aneurysms, it is sometimes
      difficult to introduce and stabilize microcatheter tips in the aneurysms. We
      report a new technique for shaping microcatheter tips in the coil embolization of
      paraclinoid aneurysms. METHODS: From May 2007 to May 2008, this new technique was
      applied to 10 paraclinoid aneurysms undergoing coil embolization. Before coil
      embolization, 3D rotational angiography was performed, and volume-rendering
      images were reconstructed. Vinyl-coated handicraft wire was shaped 3
      dimensionally to fit full-scale volume-rendering images on the monitor, from the
      C5 portion of the internal carotid artery to the center of the dome of the
      aneurysm from various angles. The microcatheter tip was then shaped with steam to
      fit the vinyl-coated wire. Thereafter, the microcatheter tip was introduced into
      the aneurysm and coil embolization was performed. RESULTS: Microcatheter tips
      could be easily shaped and could be introduced smoothly into aneurysms, and were
      stable during coil embolization. CONCLUSION: This technique is feasible for
      shaping microcatheter tips precisely for coil embolization of paraclinoid
      aneurysms.

PMID- 19838978
TI  - Does the hip reflect the centre of mass swimming kinematics?
AB  - The purpose of this study was to determine the relationship between the hip point
      and the centre of mass for kinematical parameters (displacement, velocity and
      acceleration) in the three axes of motion. One complete stroke cycle was analyzed
      in eight swimmers performing a 25 m front crawl swim test at high intensity.
      Within-subject correlation coefficients were computed between the centre of mass
      and both hips, as well as mean of the errors, RMS error and a paired sample t
      test. High correlation coefficients were found for the displacement in the
      horizontal direction (r=1.00 for both hips) and low to moderate correlation
      coefficients (r=-0.01 to r=0.54) were found for all other studied variables.
      Moreover, moderate to large RMS errors were observed: (i) between 0.05 and 0.15
      for the displacement; (ii) between 0.16 and 0.30 for the velocity and (iii)
      between 5.28 and 7.86 for the acceleration. Complementarily, RMS errors for the
      intracyclic velocity variation were between 0.07 and 0.18. Considering the centre
      of mass and hip values statistical differences were found in velocity in x,
      acceleration in x and y, and intracyclic velocity variation in y axes. Therefore,
      results suggest that the hip point does not represent most kinematical parameters
      of the estimated centre of mass in front crawl swimming.

PMID- 19838979
TI  - The relationship between gait transition speed and the aerobic thresholds for
      walking and running.
AB  - We studied the relationship between the speed at the gas exchange thresholds for
      walking and running and the preferred gait transition speed (PTS), and the
      correspondence of PTS and energetically optimal transition speed (EOTS). Twenty
      two men (age: 21.4+/-2.4 years, mass: 78.1+/-8.2 kg) performed four tests during
      which we determined VO (2max), walking/running gas exchange thresholds, walk-to
      run/run-to-walk PTS, and EOTS. There were no significant differences ( P>0.05)
      between PTS, and the speed at the aerobic threshold for walking (AeT (w)) and
      running (AeT (r)). Both walk-to-run and run-to-walk PTS significantly correlated
      to AeT (r) (r=0.82 and 0.79; P<0.01) but not to AeT (w) (r=-0.03 and 0.06;
      P>0.05). Finally, EOTS and the corresponding VO (2) were significantly higher (
      P<0.05) than the speed and VO (2) at PTS. Our results indicate that running
      rather than walking dynamics determines gait transitions in men.

PMID- 19838980
TI  - [Autism: the other side learns to accept it].

PMID- 19838981
TI  - Prolonged culture of human islets induces ER stress.
AB  - Type 2 diabetes (T2D) is characterized by islet dysfunction and beta-cell
      deficiency caused by apoptosis. One mechanism underlying induction of beta-cell
      apoptosis is stress in the endoplasmic reticulum (ER). Isolated human islets are
      a frequently used model to examine islet pathophysiology in T2D. Therefore it is
      important to establish how function and beta-cell turnover of human islets change
      in culture. Islets from four organ donors were cultured over four weeks. At 0, 1,
      2, 3 and 4 weeks aliquots of islets were used for analysis of a) islet-cell
      turnover (replication by Ki-67 and apoptosis by TUNEL staining), b) the ER stress
      level (CHOP and phospho-eIF2alpha staining), c) fractional beta-cell content
      (insulin staining) and d) islet function (2 h static incubation). Culture
      duration positively correlated to replication (p=0.03) and negatively correlated
      to apoptosis (p=0.003). In comparison to islets in situ islet cell turnover is
      accelerated (>10-fold). The ER stress level was stable during the first three
      weeks, but showed a sharp increase (p<0.05) at four weeks. The fractional beta
      cell content increased from 29+/-2% to 41+/-2% (p=0.0004). Islet function
      improved (p<0.0001). In conclusion, isolated human islets may be used for in
      vitro experiments for up to three weeks. During this time islet function and
      islet-cell turnover are stable. If islet culture is extended beyond three weeks
      ER stress may impair islet viability. Studies analyzing the pathophysiology of
      human T2D at the level of the endocrine pancreas need to confirm results obtained
      with isolated human islets by analysis of primary human pancreatic tissue.

PMID- 19838982
TI  - Spontaneous thrombosis of a saccular iliac artery aneurysm induced by overlapping
      self-expandable bare metallic stents.
AB  - Isolated iliac artery aneurysms are rare lesions. Prompt diagnosis and timely
      intervention are essential in their management. In elderly patients with
      coexisting medical problems, endovascular procedures are preferred to avoid the
      risks of morbidity and mortality associated with general anesthesia and surgery.
      We report a case of a true saccular external iliac artery aneurysm that underwent
      spontaneous thrombosis after treatment with placement of two overlapping bare
      self-expandable metallic stents only.

PMID- 19838983
TI  - Acute sarcoid myositis with unusual radiologic findings.
AB  - A 59-year-old man presented with bilateral calf pain and swelling for two weeks.
      Ultrasound and magnetic resonance imaging examination showed multiple bilateral,
      nodular, and spindle- shaped lesions in the gastrocnemius and soleus muscles. On
      physical examination, hyperpigmented, papular lesions were noticed; biopsy of the
      skin of his right elbow showed granulomatous inflammation. His angiotensin
      converting enzyme level was markedly elevated. Computed tomography showed diffuse
      interstitial thickening, miliary nodules, and traction bronchiectases throughout
      the lung parenchyma. Ophthalmologic examination showed uveitis in his left eye.
      Based on the lung, eye, and skin findings, a clinical diagnosis of sarcoidosis
      was made. After two months of corticosteroid treatment, his muscle lesions
      largely resolved.

PMID- 19838984
TI  - Renal emphysema in diabetic patients: CT evaluation.
AB  - Renal emphysema is a rare, fulminant, suppurative infection of pelvicaliceal
      system, renal parenchyma, perinephric tissues, and retroperitoneum. It is
      characterized by formation of gas. Invariably this condition is associated with
      diabetes mellitus and carries high mortality (40-90%). Renal emphysema can be
      classified into two distinct clinical entities: emphysematous pyelitis and
      emphysematous pyelonephritis. This classification has important prognostic and
      therapeutic implications. Herein we describe the computed tomographic findings in
      five unilateral cases of renal emphysema (two cases of emphysematous pyelitis and
      three cases of emphysematous pyelonephritis) in five insulin-dependent diabetic
      patients.

PMID- 19838985
TI  - Conservative treatment of a cervical twin pregnancy with uterine artery
      embolization.
AB  - Cervical pregnancy is a rare form of ectopic pregnancy. Its treatment has been
      described by different authors. We report our successful experience of a cervical
      twin pregnancy that was diagnosed by transabdominal and transvaginal ultrasound
      and confirmed by magnetic resonance imaging. To preserve fertility, our patient
      was treated by a bilateral hyperselective uterine artery embolization followed by
      dilatation and curettage of the cervical canal without ancillary procedures for
      cervical hemostasis. Arterial embolization by a resorbable agent reduces arterial
      circulation by providing a temporary occlusion of the vessels in order to
      decrease the risk of massive hemorrhage.

PMID- 19838986
TI  - CT angiography of systemic to pulmonary venous shunt in superior vena cava
      obstruction.
AB  - Superior vena cava obstruction is associated with multiple venous collaterals.
      There is an unusual pathway involving pulmonary venous collaterals in which
      systemic veins drain directly into the left heart, resulting in a right-to-left
      shunt. We report here a rare case of systemic to pulmonary venous shunt on both
      hemithoraces in superior vena cava obstruction associated with Budd-Chiari
      syndrome due to coagulopathy which was diagnosed by multidetector computed
      tomography angiography.

PMID- 19838987
TI  - Multiseptate gallbladder in a child with recurrent abdominal pain.
AB  - Multiseptate gallbladder, a rare congenital anomaly, can present with recurrent
      abdominal pain. Ultrasonography is the preferred imaging technique in patients
      with abdominal pain, especially for the evaluation of the gallbladder. We present
      the sonographic appearance of a multiseptate gallbladder.

PMID- 19838988
TI  - Traumatic lumbar artery pseudoaneurysm: the role of CT angiography in diagnosis
      and treatment.
AB  - Pseudoaneurysm of lumbar artery is a rare and late complication of penetrating
      trauma. We report the Doppler ultrasonography and multidetector computed
      tomography angiography findings and endovascular embolization treatment of a
      pseudoaneurysm of lumbar artery in a 14-year-old girl following a gunshot wound.

PMID- 19838989
TI  - Tongue metastasis mimicking an abscess.
AB  - Primary tumors metastasizing to the oral cavity are extremely rare. Lung is one
      of the most common primary sources of metastases to the tongue. Although the
      incidence of lung cancer is increasing, tongue metastasis as the initial
      presentation of the tumor remains uncommon. Due to the rarity of tongue
      metastasis, little is known about its imaging findings. Herein we report the
      magnetic resonance imaging and clinical findings of a lingual metastasis,
      mimicking an abscess, from a primary lung cancer.

PMID- 19838990
TI  - Round ligament varicosities mimicking inguinal hernias in pregnancy: importance
      of color Doppler sonography.
AB  - Round ligament varicosities are easily misdiagnosed as an obstructed hernia in a
      gravid patient. When this condition is diagnosed correctly, unnecessary
      intervention may be prevented. We aimed to determine the significance of round
      ligament varicosities in pregnancy and to describe their clinical presentation
      and sonographic appearance.

PMID- 19838991
TI  - Esophageal gastrointestinal stromal tumor with pulmonary and bone metastases.
AB  - Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the
      gastrointestinal tract. One to three percent of GISTs occur in the esophagus.
      GISTs have a great potential for diffuse intra- abdominal spread and liver
      metastasis, which are the two most common modes of dissemination. Metastases to
      other sites, especially the bones and lung, are relatively rare. Never has an
      esophageal GIST been documented to present with pulmonary and bone metastases. We
      present an unusual case of an esophageal GIST with pulmonary and bone lesions. We
      include a review of the literature.

PMID- 19838992
TI  - Cervical aortic arch in a patient with Turner syndrome.
AB  - We report a case of a young girl with Turner syndrome presenting with a pulsatile
      left-sided supraclavicular swelling since birth, which proved to be the rare
      anomaly of a cervical aortic arch. Though elongation of the transverse aortic
      arch is well known in Turner syndrome, to the best of our knowledge, a cervical
      aortic arch has not been described in the literature.

PMID- 19838993
TI  - CT and MRI of intraperitoneal splenosis.
AB  - Splenosis is a condition in which ectopic spleen tissue may be found in the
      peritoneal cavity or in other unusual locations due to heterotopic auto
      transplantation and implantation of splenic tissue after splenic trauma or
      splenectomy. It is a benign condition that is often misdiagnosed as a tumor;
      therefore, knowledge of this condition is important when evaluating patients with
      a history of splenic trauma or splenectomy and newly appearing peritoneal
      lesions. Herein, we describe computed tomography and magnetic resonance imaging
      findings of two cases of subdiaphragmatic intraperitoneal splenosis located along
      the hepatic surface, mimicking neoplastic lesions.

PMID- 19838994
TI  - CT urography of a vesicourachal diverticulum containing calculi.
AB  - Urachal remnant disease is a relatively rare urological condition that presents a
      variety of clinical problems in adult patients. Contrast-enhanced multi-detector
      row computed tomography (MDCT) urography is a new diagnostic imaging technique
      providing comprehensive evaluation of the upper and lower urinary tract. MDCT
      urography performed with a combination of unenhanced, nephrographic phase, and
      excretory- phase imaging can demonstrate a wide spectrum of disease in these
      patients with a single study. We report a case of vesicourachal diverticulum
      containing calculus, which was diagnosed by MDCT urography.

PMID- 19838995
TI  - Concepts and synonymy in the UMLS Metathesaurus.
AB  - This paper advances a detailed exploration of the complex relationships among
      terms, concepts, and synonymy in the UMLS Metathesaurus, and proposes the study
      and understanding of the Metathesaurus from a model-theoretic perspective.
      Initial sections provide the background and motivation for such an approach, and
      a careful informal treatment of these notions is offered as a context and basis
      for the formal analysis. What emerges from this is a set of puzzles and
      confusions in the Metathesaurus and its literature pertaining to synonymy and its
      relation to terms and concepts. A model theory for a segment of the Metathesaurus
      is then constructed, and its adequacy relative to the informal treatment is
      demonstrated. Finally, it is shown how this approach clarifies and addresses the
      puzzles educed from the informal discussion, and how the model-theoretic
      perspective may be employed to evaluate some fundamental criticisms of the
      Metathesaurus. For users of the UMLS, two significant results of this analysis
      are a rigorous clarification of the different senses of synonymy that appear in
      treatments of the Metathesaurus and an illustration of the dangers in computing
      inferences involving ambiguous terms.

PMID- 19838996
TI  - Tracking the current rise of chinese pharmaceutical bionanotechnology.
AB  - BACKGROUND: THE CONTEXT AND PURPOSE OF THE STUDY: Over the last decade China has
      emerged as a major producer of scientific publications, currently ranking second
      behind the US. During that time Chinese strategic policy initiatives have placed
      indigenous innovation at the heart of its economy while focusing internal R&D
      investments and the attraction of foreign investment in nanotechnology as one of
      their four top areas. China's scientific research publication and nanotechnology
      research publication production has reached a rank of second in the world, behind
      only the US. Despite these impressive gains, some scholars argue that the quality
      of Chinese nanotech research is inferior to US research quality due to lower
      overall times cited rates, suggesting that the US is still the world leader. We
      combine citation analysis, text mining, mapping, and data visualization to gauge
      the development and application of nanotechnology in China, particularly in
      biopharmananotechnology, and to measure the impact of Chinese policy on
      nanotechnology research production. RESULTS, THE MAIN FINDINGS: Our text mining
      based methods provide results that counter existing claims about Chinese
      nanotechnology research quality. Due in large part to its strategic innovation
      policy, China's output of nanotechnology publications is on pace to surpass US
      production in or around 2012.A closer look at Chinese nanotechnology research
      literature reveals a large increase in research activity in China's
      biopharmananotechnology research since the implementation in January, 2006 of
      China's Medium & Long Term Scientific and Technological Development Plan
      Guidelines for the period 2006-2020 ("MLP"). CONCLUSIONS, BRIEF SUMMARY AND
      POTENTIAL IMPLICATIONS: Since the implementation of the MLP, China has enjoyed a
      great deal of success producing bionano research findings while attracting a
      great deal of foreign investment from pharmaceutical corporations setting up
      advanced drug discovery operations. Given the combination of current scientific
      production growth as well as economic growth, a relatively low scientific
      capacity, and the ability of its policy to enhance such trends, China is in some
      sense already the new world leader in nanotechnology. Further, the Chinese
      national innovation system may be the new standard by which other national S&T
      policies should be measured.

PMID- 19838997
TI  - [Evaluation of nursing processes in psychiatry--a field study project].
AB  - Professional nursing care can be characterised as a support in handling of and
      coping with activities of daily living. While somatic care mainly focusses on the
      compensation of physical complaints, the needs in the field of psychiatry leading
      to nursing interventions are quite different. The descriptive and explorative
      study presented here aims at finding typical needs for psychiatric nursing care
      and characteristic intervention patterns of nurses. Within the setting of a
      qualitative field study in an anthroposophically oriented hospital for mental
      disorders heuristic methods (Grounded Theory) were applied to evaluate those
      nursing events which induced a unique and specific nursing benefit. The narrative
      data from 59 episodes generated this way yielded four typical patterns of
      interpretation of nursing needs: integration versus autonomy and routine nursing
      versus crisis intervention. Our results are limited by the fact that only data of
      one hospital were analysed. However, due to quality control of internal and
      external validity, and adjustment of the results towards current findings it can
      be concluded that the study results have a heuristic potential for describing and
      precising other settings within and outside psychiatric care.

PMID- 19838998
TI  - Antioxidant effect on urinary excretion of malondialdehyde in non-athletes during
      aerobic training.
AB  - Conditions in the body during aerobic exercise increase the level of lipid
      peroxidation (LP). LP is associated with elevated concentration of modified low
      density lipoproteins that are implicated in development of cardiovascular
      disease. Supplementation with antioxidant vitamin E to athletes at 267 mg (400
      IUs) or greater has been reported to reduce levels of LP associated with
      exercise. Little is currently known about the effects of modest supplementation
      of vitamin E on previously sedentary adults who initiate an aerobic fitness
      program. In the present study, sedentary subjects (n = 14) kept 24-hour diet
      records to establish antioxidant intake of vitamins E and C and collected 24-hour
      urine samples that were used to determine baseline urinary malondialdehyde (MDA)
      concentrations, one measure of in vivo LP. No significant differences were noted
      in the parameters between groups. Seven subjects were randomly selected and
      supplemented daily with 133 mg (200 IUs) of vitamin E. All subjects participated
      in moderate-intensity aerobic training for 8 weeks. Post-training, non
      supplemented subjects excreted significantly more MDA (p<0.05) and consumed
      significantly fewer antioxidants than the supplemented group. Vitamin E
      supplementation appears to suppress elevated LP associated with beginning an
      aerobic exercise regimen in previously sedentary subjects.

PMID- 19838999
TI  - Diet determines features of the metabolic syndrome in 6- to 14-year-old children.
AB  - BACKGROUND/OBJECTIVES: Insulin resistance (IR) and hypertension are common in
      overweight children, and the adipocyte-derived hormones resistin, adiponectin,
      and leptin may modulate IR and blood pressure (BP). Few data exist in children on
      dietary determinants of IR, BP, or leptin, and no data exist on dietary
      determinants of resistin and adiponectin. Therefore, the objective of this study
      was to investigate dietary determinants of IR, BP, resistin, adiponectin, and
      leptin concentrations, as well as the interrelationship among these variables, in
      normal and overweight children. SUBJECTS/METHODS: In 6- to 14-year-old Swiss
      children (n=79), nutritional intake was assessed using two 24-hour-recalls and a
      one-day dietary record. Body mass index (BMI), body fat percentage (BF%),
      waist/hip ratio (W/H ratio), BP, glucose, insulin, resistin, adiponectin, and
      leptin were determined. IR was calculated using the quantitative insulin
      sensitivity check index (QUICKI). RESULTS: BMI, BF%, and W/H ratio were
      significant predictors of leptin and insulin, QUICKI, and systolic BP, but not
      resistin or adiponectin. Of the overweight and obese children, 40% were diagnosed
      pre-hypertensive or hypertensive. Total energy, fat, saturated fat, and protein
      intakes were significant predictors of fasting insulin and QUICKI, and total fat,
      saturated fat, and monounsaturated fat intakes were significant predictors of
      systolic BP, independent of BMI standard deviation score (BMI-SDS) and age. There
      were no associations between these dietary factors and leptin, adiponectin, or
      resistin. CONCLUSION: In children, dietary macronutrient composition is a
      predictor of IR and systolic BP, but not resistin, adiponectin, or leptin
      concentrations. Resistin and adiponectin concentrations are not correlated with
      IR or BP in this age range.

PMID- 19839000
TI  - Effects of 3-week consumption of green tea extracts on whole-body metabolism
      during cycling exercise in endurance-trained men.
AB  - The consumption of green tea has been generally associated with beneficial
      effects on human whole-body metabolism and recent investigations with animals
      indicate favorable effects of green tea extracts (GTE) on energy metabolism
      during exercise and aerobic exercise performance. Therefore, the purpose of this
      study was to examine the effects of a three-week supplementation with GTE on
      human energy metabolism during submaximal cycling exercise. In a randomized,
      double-blind crossover setting, ten healthy endurance-trained men exercised for 2
      hours at 50 % W(max) before and after three weeks of placebo or GTE
      supplementation (GTE containing about 160 mg x day(-1) total catechins, of which
      about 70 mg x day(-1) was epigallocatechin-3-gallate). The GTE supplementation
      did not influence indices of fat and energy metabolism (fatty acids, 3-beta
      hydroxybutyrate, triacylglycerol, low-density-lipoprotein cholesterol, total
      cholesterol, lactate, glucose, oxygen uptake, respiratory exchange ratio, energy
      expenditure), inflammation processes (interleukin-6, C-reactive protein), and
      oxidative stress (thiobarbituric-acid reactive substances, oxidized low-density
      lipoprotein cholesterol), but plasma creatine kinase concentration at rest and
      during exercise was significantly lower (p = 0.039) and high-density-lipoprotein
      cholesterol concentration at rest was significantly higher (p = 0.043) compared
      to placebo. In conclusion, these results suggest only slight effects on whole
      body metabolism after supplementation with GTE.

PMID- 19839001
TI  - Effect of fenugreek seeds on blood glucose and lipid profiles in type 2 diabetic
      patients.
AB  - BACKGROUND: Recently use of herbal medicines, have been considered as an
      alternative for therapeutic usage. So, this study was undertaken to evaluate the
      hypoglycemic and hypolipidemic effects of fenugreek seeds in type 2 diabetic
      patients. METHODS: In a clinical trial study, 24 type 2 diabetic patients were
      placed on 10 grams/day powdered fenugreek seeds mixed with yoghurt or soaked in
      hot water for 8 weeks. Weight, FBS, HbA(1)C, total cholesterol, LDL, HDL and food
      record were measured before and after the study. The differences observed in food
      records, BMI and serum variables were analyzed using paired-t-test and t-student
      and P<or=0.05 was considered as significant. RESULTS: After exclusion of 6 cases
      for changing in medication or personal problems, the results of 18 patients (11
      consumed fenugreek in hot water and 7 in yoghurt) were studied. Findings showed
      that FBS, TG and VLDL-C decreased significantly (25 %, 30 % and 30.6 %
      respectively) after taking fenugreek seed soaked in hot water whereas there were
      no significantly changes in lab parameters in cases consumed it mixed with
      yoghurt. BMI, Energy, Carbohydrate, Protein and fat intake remained unchanged
      during study. CONCLUSION: This study shows that fenugreek seeds can be used as an
      adjuvant in the control of type 2 diabetes mellitus in the form of soaked in hot
      water.

PMID- 19839002
TI  - The vitamin A status of Zambian children in a community of vitamin A
      supplementation and sugar fortification strategies as measured by the modified
      relative dose response (MRDR) test.
AB  - The main objective of the study was to determine the vitamin A status of Zambian
      children less than five years of age in a community where strategies of vitamin A
      supplementation and consumption of vitamin A fortified sugar have been
      introduced. In a cross-sectional study, a total of 537 children were enrolled.
      Their vitamin A status was measured using the modified relative dose response
      (MRDR) test. Their vitamin A status was compared to the status measured using a
      similar method in 1996, before vitamin A supplementation through capsule
      distribution and fortification of sugar was implemented as strategies to reduce
      vitamin A deficiency in the country. Results showed that the vitamin A status of
      children improved markedly as a result of these strategies.

PMID- 19839003
TI  - Bitter melon protects against lipid peroxidation caused by immobilization stress
      in albino rats.
AB  - In the present study, protective effects of bitter melon (Momordica charantia)
      extract on lipid peroxidation induced by immobilization stress in rats have been
      assessed. Graded doses of extract (50, 100, and 150 mg/kg body weight) were
      administered orally to rats subjected to immobilization stress for two hours for
      seven consecutive days. Stress was applied by keeping the rats in a cage where no
      movement was possible. After seven days, rats were killed by decapitation after
      ether anesthesia. Blood and liver were collected to measure thiobarbituric acid
      reactive substances, reduced glutathione, and catalase. In vitro effects of M.
      charantia extract on lipid peroxidation in liver homogenate of normal, control,
      and rats pretreated with extract were carried out against cumene hydroperoxide
      induced lipid peroxidation. Results reveal that in vivo M. charantia inhibited
      stress-induced lipid peroxidation by increasing the levels of reduced glutathione
      and activities of catalase. These results were further supported by in vitro
      results. In vitro inhibition of lipid peroxidation was indicated by low levels of
      thiobarbituric acid in the liver homogenate from pretreated rats and normal rats
      when incubated with both cumene hydroperoxide and extract. Inhibition was also
      noted in the homogenate where the rats were pretreated but the mixture contained
      no extract. Thus this plant provides protection by strengthening the antioxidants
      like reduced glutathione and catalase. Inclusion of this plant in the daily diet
      would be beneficial.

PMID- 19839004
TI  - Oral medications with significant hepatic metabolism at higher risk for hepatic
      adverse events.
AB  - Reactive metabolites generated by hepatic metabolism are thought to play an
      important role in the pathogenesis of drug-induced liver injury (DILI), but
      supporting data are limited. If this is true, then compounds with significant
      hepatic metabolism should cause more DILI than those without it. We conducted a
      study to examine the relationship between hepatic metabolism and DILI of
      prescription medications. We systematically extracted the metabolism
      characteristics of 207 of the most widely prescribed oral medications in the
      United States. Compounds with >50% hepatic metabolism were characterized as those
      with significant hepatic metabolism (n = 149). Hepatic adverse events of interest
      were alanine aminotransferase >3 times the upper limit of normal, jaundice, liver
      failure, liver transplantation, or fatal DILI. Compared with compounds with
      lesser hepatic metabolism, compounds belonging to the significant hepatic
      metabolism group had significantly higher frequency of alanine aminotransferase
      >3 times the upper limit of normal (35% versus 11%, P = 0.001), liver failure
      (28% versus 9%, P = 0.004), and fatal DILI (23% versus 4%, P = 0.001), but not
      jaundice (46% versus 35%, P = 0.2) or liver transplantation (9% versus 2%, P =
      0.11). Twelve compounds with no hepatic metabolism had no reports of liver
      failure, liver transplantation, or fatal DILI. When the relationship between
      hepatic adverse events and combination of hepatic metabolism and daily dose was
      examined, compounds with both significant hepatic metabolism and daily dose >50
      mg (n = 50) were significantly more hepatotoxic than compounds belonging to other
      groups. Compared with medications without biliary excretion, compounds with
      biliary excretion (n = 50) had significantly higher frequency of jaundice (74%
      versus 40%, P = 0.0001). CONCLUSION: Our study finds an important relationship
      between a compound's metabolism profile and reports of hepatic adverse events.

PMID- 19839005
TI  - The heat shock protein inhibitor Quercetin attenuates hepatitis C virus
      production.
AB  - The hepatitis C viral (HCV) genome is translated through an internal ribosome
      entry site (IRES) as a single polyprotein precursor that is subsequently cleaved
      into individual mature viral proteins. Nonstructural protein 5A (NS5A) is one of
      these proteins that has been implicated in regulation of viral genome
      replication, translation from the viral IRES and viral packaging. We sought to
      identify cellular proteins that interact with NS5A and determine whether these
      interactions may play a role in viral production. Mass spectrometric analysis of
      coimmunoprecipitated NS5A complexes from cell extracts identified heat shock
      proteins (HSPs) 40 and 70. We confirmed an NS5A/HSP interaction by confocal
      microscopy demonstrating colocalization of NS5A with HSP40 and with HSP70.
      Western analysis of coimmunoprecipitated NS5A complexes further confirmed
      interaction of HSP40 and HSP70 with NS5A. A transient transfection, luciferase
      based, tissue culture IRES assay demonstrated NS5A augmentation of HCV IRES
      mediated translation, and small interfering RNA (siRNA)-mediated knockdown of
      HSP70 reduced this augmentation. Treatment with an inhibitor of HSP synthesis,
      Quercetin, markedly reduced baseline IRES activity and its augmentation by NS5A.
      HSP70 knockdown also modestly reduced viral protein accumulation, whereas HSP40
      and HSP70 knockdown both reduced infectious viral particle production in an HCV
      cell culture system using the J6/JFH virus fused to the Renilla luciferase
      reporter. Treatment with Quercetin reduced infectious particle production at
      nontoxic concentrations. The marked inhibition of virus production by Quercetin
      may partially be related to reduction of HSP40 and HSP70 and their potential
      involvement in IRES translation, as well as viral morphogenesis or secretion.
      CONCLUSION: Quercetin may allow for dissection of the viral life cycle and has
      potential therapeutic use to reduce virus production with low associated
      toxicity.

PMID- 19839006
TI  - Microbial induction of inflammatory bowel disease associated gene TL1A (TNFSF15)
      in antigen presenting cells.
AB  - TL1A is a member of the TNF superfamily and its expression is increased in the
      mucosa of inflammatory bowel disease patients. Neutralizing anti-mouse TL1A Ab
      attenuates chronic colitis in two T-cell driven murine models, suggesting that
      TL1A is a central modulator of gut mucosal inflammation in inflammatory bowel
      disease. We showed previously that TL1A is induced by immune complexes via the Fc
      gamma R signaling pathway. In this study, we report that multiple bacteria,
      including gram negative organisms (E. coli, E. coli Nissle 1917, Salmonella
      typhimurium), gram positive organisms (Listeria monocytogenes, Staphylococcus
      epidermidis), partial anaerobes (Campylobacter jejuni), and obligate anaerobes
      (Bacteroides thetaiotaomicron, Bifidobacterium breve, Clostridium A4) activate
      TL1A expression in human APC, including monocytes and monocyte-derived DC.
      Bacterially induced TL1A mRNA expression correlates with the detection of TL1A
      protein levels. TL1A induced by bacteria is mediated in part by the TLR signaling
      pathway and inhibited by downstream blockade of p38 MAPK and NF-kappaB
      activation. Microbial induction of TL1A production by human APC potentiated
      CD4(+) T-cell effector function by augmenting IFN-gamma production. Our findings
      suggest a role for TL1A in pro-inflammatory APC-T cell interactions and implicate
      TL1A in host responses to enteric microorganisms.

PMID- 19839007
TI  - Curcumin induces the tolerogenic dendritic cell that promotes differentiation of
      intestine-protective regulatory T cells.
AB  - The gut is home to a large number of Treg, with both CD4(+) CD25(+) Treg and
      bacterial antigen-specific Tr1 cells present in normal mouse intestinal lamina
      propria. It has been shown recently that intestinal mucosal DC are able to induce
      Foxp3(+) Treg through production of TGF-beta plus retinoic acid (RA). However,
      the factors instructing DC toward this mucosal phenotype are currently unknown.
      Curcumin has been shown to possess a number of biologic activities including the
      inhibition of NF-kappaB signaling. We asked whether curcumin could modulate DC to
      be tolerogenic whose function could mimic mucosal DC. We report here that
      curcumin modulated BM-derived DC to express ALDH1a and IL-10. These curcumin
      treated DC induced differentiation of naive CD4(+) T cells into Treg resembling
      Treg in the intestine, including both CD4(+)CD25(+) Foxp3(+) Treg and IL-10
      producing Tr1 cells. Such Treg induction required IL-10, TGF-beta and retinoic
      acid produced by curcumin-modulated DC. Cell contact as well as IL-10 and TGF
      beta production were involved in the function of such induced Treg. More
      importantly, these Treg inhibited antigen-specific T-cell activation in vitro and
      inhibited colitis due to antigen-specific pathogenic T cells in vivo.

PMID- 19839008
TI  - Depletion of tumor-induced Treg prior to reconstitution rescues enhanced priming
      of tumor-specific, therapeutic effector T cells in lymphopenic hosts.
AB  - We reported previously that vaccination of reconstituted, lymphopenic mice
      resulted in a higher frequency of tumor-specific effector T cells with
      therapeutic activity than vaccination of normal mice. Here, we show that
      lymphopenic mice reconstituted with spleen cells from tumor-bearing mice (TBM), a
      situation that resembles the clinical condition, failed to generate tumor
      specific T cells with therapeutic efficacy. However, depletion of CD25(+) Treg
      from the spleen cells of TBM restored tumor-specific priming and therapeutic
      efficacy. Adding back TBM CD25(+) Treg to CD25(-) naive and TBM donor T cells
      prior to reconstitution confirmed their suppressive role. CD25(+) Treg from TBM
      prevented priming of tumor-specific T cells since subsequent depletion of CD4(+)
      T cells did not restore therapeutic efficacy. This effect may not be antigen
      specific as three histologically distinct tumors generated CD25(+) Treg that
      could suppress the T-cell immune response to a melanoma vaccine. Importantly,
      since ex vivo depletion of CD25(+) Treg from TBM spleen cells prior to
      reconstitution and vaccination fully restored the generation of therapeutic
      effector T cells, even in animals with established tumor burden, we have
      initiated a translational clinical trial of this strategy in patients with
      metastatic melanoma.

PMID- 19839009
TI  - Monocyte and neutrophil recruitment during oral Salmonella infection is driven by
      MyD88-derived chemokines.
AB  - Oral Salmonella infection recruits phagocytes to Peyer's patches (PP) and MLN.
      The chemokines induced in infected PP and MLN, the cellular sources during
      infection and the TLR signaling pathways involved in vivo are not known. Here, we
      show that CCL2, CXCL9 and CXCL2 mRNA are up-regulated in PP and MLN coincident
      with the first arrival of monocytes and neutrophils. Laser capture
      microdissection microscopy revealed that chemokine mRNA up-regulation was
      differently distributed in PP. Despite this, recruited monocytes and neutrophils
      formed inflammatory cell clusters throughout PP. Monocytes and neutrophils
      purified from infected mice preferentially produced CXCL2 and small amounts of
      CCL2, and neutrophils from infected mice migrated towards CXCL2 and CCL3.
      Furthermore, phagocyte recruitment to PP and MLN was intact in mice lacking TLR4
      alone and when signaling through TLR4 and TLR5 was simultaneously absent;
      however, recruitment was compromised in MyD88(-/-) and more so in MyD88(-/-)TLR4(
      /-) double knockout mice. Phagocyte release into the blood, however, was only
      marginally reduced in MyD88(-/-)TLR4(-/-) mice. Defective phagocyte recruitment
      to PP and MLN of MyD88(-/-)TLR4(-/-) mice was paralleled by low chemokine
      induction. These data provide insight into the chemokines and TLR signaling
      pathways that orchestrate the early phagocyte response to oral Salmonella
      infection.

PMID- 19839010
TI  - Treg suppress CTL responses upon immunization with HSP gp96.
AB  - HSP gp96-based vaccines have been trialled in rodent models and, more recently,
      in humans. Better understanding of gp96's immunomodulatory role will help with
      the design of more effective strategies for treatment of cancer and infectious
      diseases. In this study, we monitored the activities of T cells and activation of
      Treg in BABL/c mice after immunization using different doses of gp96 as adjuvant.
      We found that co-injection of gp96 simultaneously stimulated both CTL and Treg
      activity. Activation of CTL at low dose was far more pronounced than Treg
      activation. Treg population and suppression increased with gp96 dose, eventually
      abrogating the T-cell response induced by immunization. Low-dose cyclophosphamide
      treatment could restore the T-cell responses lost after high-dose gp96 adjuvant
      injection by suppression of Treg activation. We further examined the effect of
      different doses of gp96 or N355 peptide administration on tumor rejection. Our
      results provide new insights into the mechanisms of gp96-mediated balance between
      regulatory and responder T cells, which may facilitate future development of an
      effective gp96-based therapeutic vaccine.

PMID- 19839011
TI  - Nuclear retention of IL-1 alpha by necrotic cells: a mechanism to dampen sterile
      inflammation.
AB  - Sterile inflammation is a host response to tissue injury that is mediated by
      damage-associated molecular patterns released from dead cells. Sterile
      inflammation worsens damage in a number of injury paradigms. The pro-inflammatory
      cytokine IL-1 alpha is reported to be a damage-associated molecular pattern
      released from dead cells, and it is known to exacerbate brain injury caused by
      stroke. In the brain, IL-1 alpha is produced by microglia, the resident brain
      macrophages. We found that IL-1 alpha is actively trafficked to the nuclei of
      microglia, and hence tested the hypothesis that trafficking of IL-1 alpha to the
      nucleus would inhibit its release following necrotic cell death, limiting sterile
      inflammation. Microglia subjected to oxygen-glucose deprivation died via
      necrosis. Under these conditions, microglia expressing nuclear IL-1 alpha
      released significantly less IL-1 alpha than microglia with predominantly
      cytosolic IL-1 alpha. The remaining IL-1 alpha was immobilized in the nuclei of
      the dead cells. Thus, nuclear retention of IL-1 alpha may serve to limit
      inflammation following cell death.

PMID- 19839012
TI  - Paramedical treatment in primary dystonia: a systematic review.
AB  - Dystonia is a disabling movement disorder with a significant impact on quality of
      life. The current therapeutic armamentarium includes various drugs, botulinum
      toxin injections, and occasionally (neuro)surgery. In addition, many patients are
      referred for paramedical (including allied health care) interventions. An
      enormous variation in the paramedical treatment is provided, largely because
      evidence-based, accepted treatment regimes are not available. We have conducted a
      systematic review of studies that explored the effect of various paramedical
      interventions in primary dystonia. Only studies that have used clinical outcome
      measures were included. There were no class A1 or A2 studies and therefore, level
      1 or 2 practice recommendations for a specific intervention could not be
      deducted. Many papers were case reports, mostly with a very limited number of
      patients and a clear publication bias for beneficial effects of a particular
      paramedical intervention. Some potentially interesting interventions come from
      class B studies, which include physical therapy in addition to botulinum toxin
      injections (BoNT-A) in cervical dystonia; sensorimotor training and
      transcutaneous electrical nerve stimulation (TENS) in writer's cramp; and speech
      therapy added to BoNT-A injections in laryngeal dystonia. Good quality clinical
      studies are therefore warranted, which should have the aim to be generally
      applicable. A design in which the paramedical intervention is added to a current
      gold standard, for example, BoNT-A injections in cervical dystonia, is
      recommended.

PMID- 19839014
TI  - Utilization of dual retention mechanism on columns with bonded PEG and diol
      stationary phases for adjusting the separation selectivity of phenolic and
      flavone natural antioxidants.
AB  - The retention of phenolic acid and flavone antioxidants was investigated on three
      columns with bonded PEG, hydroxy (DIOL) and mixed oxyethylene-hydroxy (Luna
      HILIC) stationary phases in buffered aqueous ACN mobile phases. All columns show
      mixed retention mechanism: reversed phases in highly aqueous mobile phases and
      normal phases (HILIC, hydrophilic interaction LC) in mobile phases with high
      concentration of ACN, showing characteristic U-shape retention versus mobile
      phase composition plots. Equations enabling description and prediction of
      retention of sample compounds over the full mobile phase composition range were
      compared. Dual retention mechanism offers possibilities for using differences in
      selectivity between the two separation modes on a single column to improve the
      separation of natural antioxidants. The Luna HILIC column shows larger HILIC
      retention range, enhanced retention, improved selectivity and better peak
      symmetry in comparison to the PEG and DIOL columns.

PMID- 19839013
TI  - Metabolic correlatives of brain activity in a FOS epilepsy patient.
AB  - The correlation and the interactions between neuronal activity and underlying
      metabolic dynamics are still a matter of debate, especially in pathological
      conditions. This study reports findings obtained on a subject suffering from
      fixation-off sensitivity (FOS) epilepsy, exploited as a model system of
      triggerable anomalous electrical activity. Functional Magnetic Resonance
      Spectroscopy was used to investigate the metabolic response to visual spike
      inducing stimuli in a single voxel placed in the temporo-occipital lobe of a FOS
      epilepsy patient. MRS measurements were additionally performed on a control group
      of five healthy volunteers. The FOS patient also underwent an EEG session with
      the same stimulus paradigm. Uniquely in the FOS patient, glutamate and glutamine
      concentration increased during the first 10 min of stimulation and then returned
      to baseline. On the other hand, FOS-induced epileptic activity (spiking) endured
      throughout all the stimulation epoch. The observed metabolic dynamics may be
      likely linked to a complex interplay between alterations of the metabolic
      pathways of glutamate and modulation of the neuronal activity.

PMID- 19839016
TI  - On the origin of reversible hydrogen activation by phosphine-boranes.
AB  - Mechanistic insights into the factors responsible for the reversible hydrogen
      activation ability exhibited by an aryl phosphine-borane system ((CH(3))(2)P
      C(6)F(4)-B(CF(3))(2)) are presented. A detailed evaluation of the energies of
      various intermediates, generated by the addition of molecular hydrogen, and their
      interconverting barriers have been carried out using ab initio and DFT methods.
      Several rearrangement possibilities of the H(2)-phosphino-borane adduct have been
      investigated so as to unravel the lower energy pathways that convert the initial
      adduct to a series of other intermediates. The initial adduct formed by the
      heterolytic addition of a molecular hydrogen across the C-B bond is identified to
      undergo a series of rearrangement reactions until it terminates at the C-P end of
      the molecule. Among the possible 1,n-migrations (for which n=1-5), 1,2-proton
      migrations are found to possess lower energy transition states, whereas 1,2
      hydride (in a zwitterionic intermediate) and 1,4-proton-coupled electron
      transfers exhibited much higher energy transition states. The minimum energy
      pathway for the transfer of a proton and hydride from the C-B bond to the C-P
      bond is found to involve a cascade of 1,2-proton transfers followed by a 1,2
      hydride migration and finally a 1,4-proton-coupled electron transfer. The higher
      energy pathways identified for the hydride transfer suggest the possibility of a
      cascade of reversible proton migrations from a thermodynamically stable
      intermediate (M(a)). Possible uptake of two hydrogen molecules by the phosphine
      borane system is additionally considered in the present study, in which
      relatively higher barriers than those with one molecule of hydrogen are observed.
      The computed thermodynamic parameters are found to be in accordance with the
      experimental observations, in which the uptake and storage of molecular hydrogen
      are carried out at lower temperatures whereas the liberation demands elevated
      temperatures.

PMID- 19839015
TI  - Determination of paclitaxel and its analogues in the needles of Taxus species by
      using negative pressure cavitation extraction followed by HPLC-MS-MS.
AB  - A new separation method, negative pressure cavitation (NPC) extraction followed
      by HPLC-MS-MS for the determination of paclitaxel and its analogues in the
      needles of Taxus species is described in this study. Compared with three
      conventional extraction methods, NPC is a more effective, economical, and facile
      method for the separation of nature compounds from herbal plants. In contrast to
      high-temperature extraction, NPC at low temperature can minimize undesirable
      reactions such as thermal decomposition or degradation. In addition, the
      extraction mechanism of NPC was also illuminated. The effects of vacuum degree,
      extraction solvent, ratio of solid to liquid, time, and times extraction were
      studied and optimized. The optimum extraction conditions were as follows: vacuum
      degree -0.03 MPa, solvent 80% v/v alcohol, ratio of material to liquid 1:15
      (g/mL), extraction time 60 min, extraction (x3). Using these conditions, the
      recoveries of 10-deacetyl-7-xylosylpaclitaxel, 10-deacetylpaclitaxel,
      cephalomannine, and paclitaxel were higher than 95.88, 95.82, 94.85, and 96.18%,
      respectively. The contents of paclitaxel, 10-deacetyl-7-xylosylpaclitaxel, 10
      deacetylpaclitaxel, and cephalomannine for Taxus chinensis were 0.0053, 0.0467,
      0.0132, and 0.0076%, and 0.0067, 0.0153, 0.0047, and 0.0064% for Taxus cuspidata,
      respectively. Furthermore, a comparison of SEM images observed the morphological
      changes of microstructures and cellular damage in yew needles.

PMID- 19839017
TI  - Dendron-functionalized core-shell superparamagnetic nanoparticles: magnetically
      recoverable and reusable catalysts for suzuki C--C cross-coupling reactions.
AB  - A metallodendron functionalized with dicyclohexyldiphosphino palladium complex
      was synthesized. The metallodendron was grafted onto core-shell superparamagnetic
      nanoparticles (gamma-Fe(2)O(3)/polymer, 200-500 nm) to give optimal catalytic
      reactivity in cross-coupling reactions. The grafted nanoparticles were used as
      recoverable and reusable catalysts for Suzuki C--C cross-coupling reactions. They
      showed remarkable reactivity towards iodo- and bromoarenes under mild conditions,
      and unprecedented reactivity towards chloroarenes. On completion of the catalytic
      reaction, the catalysts were readily recovered by using a simple magnet to
      attract the superparamagnetic grafted nanoparticles. Catalysts were recovered
      more than 25 times with almost no discernable loss of reactivity.

PMID- 19839018
TI  - The solution structure and self-association properties of the cyclic
      lipodepsipeptide pseudodesmin A support its pore-forming potential.
AB  - Pseudodesmin A is a cyclic lipodepsipeptide (CLP) of the viscosin group with a
      moderate in vitro biological activity. For several CLPs, including members of
      this group, this activity has been related to the ability to form ion pores in
      cellular membranes. As their size does not allow individual CLPs to span the
      membrane bilayer, individual monomers must somehow assemble into a larger
      structure. NMR spectroscopy has been used to demonstrate that in chloroform and
      other apolar organic solvents, pseudodesmin A monomers assemble into a
      supramolecular structure. These self-assembled structures can become sufficiently
      large to span the membrane bilayer as demonstrated with translational diffusion
      NMR spectroscopic measurements. With the aim to obtain more insight into the
      structural nature of this assembly, the solution conformation of pseudodesmin A
      was first determined by using ROESY (rOe) restraints measured in acetonitrile, in
      which no self-association occurs. The structure, which is found to be mostly
      similar to the previously described crystal structure, is shown to be retained
      within the supramolecular complex. Intermolecular rOe contacts obtained in
      chloroform together with chemical shift perturbation data provides structural
      insight into the organization of the self-associated complex. Based upon this
      analysis, a model for the organization of pseudodesmin A monomers in the
      supramolecular assembly is proposed, which is in agreement with the formation of
      bilayer spanning hydrophilic pores and provides the basis for a structure
      function relationship for this type of CLPs. Finally, it is demonstrated that the
      differences previously reported between the crystal and solution conformation of
      the white line inducing principle (WLIP), a close analogue of pseudodesmin A, are
      the result of the use of dimethyl sulfoxide as solvent, whose strong hydrogen
      bonding capacity induces conformational exchange.

PMID- 19839020
TI  - Highly Z- and enantioselective ring-opening/cross-metathesis reactions and Z
      selective ring-opening metathesis polymerization.

PMID- 19839019
TI  - Triptycene-based metal salphens--exploiting intrinsic molecular porosity for gas
      storage.

PMID- 19839021
TI  - Total synthesis of piperazimycin A: a cytotoxic cyclic hexadepsipeptide.

PMID- 19839022
TI  - DNA condensation by field-induced non-equilibrium noise.
AB  - DNA molecules under good solvent conditions condense when subjected to strong AC
      electrical fields. It is shown that AC electrical fields couple charge
      fluctuations to molecular shape fluctuations, which produces a non-equilibrium
      noise source that can dominate over equilibrium thermal noise in the long
      wavelength limit. The field-induced excess charge fluctuations amplify the
      Asakura-Oosawa fluctuation attraction force between neighboring chains, providing
      a mechanism for field-induced DNA condensation.

PMID- 19839023
TI  - Adsorption of large organic molecules on clean and hydroxylated rutile TiO2(110)
      surfaces.
AB  - Behavior of large organic molecules equipped with spacer groups (Violet Landers,
      VL) on the TiO(2)(110)-(1x1) surfaces is investigated by means of high-resolution
      scanning tunneling microscopy (STM). Two distinct adsorption geometries are
      observed. We demonstrate that the molecule adsorption morphology can be
      alternated by well-controlled STM tip-induced manipulation. It is used to probe
      the mobility of molecules and reveals locking in one of the analyzed adsorption
      sites, thus allow to enhance or reduce the mobility along the [001] direction.
      Field induced hydrogen desorption is used to perform lateral STM manipulation on
      a hydroxyl-free surface, which provides insight into the influence of surface
      hydroxyl groups on the molecule behavior. The ability to image with submolecular
      resolution both the central board and the spacer groups of the VL molecule is
      demonstrated.

PMID- 19839024
TI  - Kinetics of hydride abstractions from 2-arylbenzimidazolines.
AB  - The rates of the hydride abstractions from the 2-aryl-1,3-dimethyl
      benzimidazolines 1a-f by the benzhydrylium tetrafluoroborates 3a-e were
      determined photometrically by the stopped-flow method in acetonitrile at 20
      degrees C. The reactions follow second-order kinetics, and the corresponding rate
      constants k2 obey the linear free energy relationship log k2(20 degrees C) =
      s(N+E), from which the nucleophile-specific parameters N and s of the 2
      arylbenzimidazolines 1a-c have been derived. With nucleophilicity parameters N
      around 10, they are among the most reactive neutral C--H hydride donors which
      have so far been parameterized. The poor correlation between the rates of the
      hydride transfer reactions and the corresponding hydricities (DeltaH0) indicates
      variable intrinsic barriers.

PMID- 19839025
TI  - Direct-oxidative DNA damage and apoptosis induction in different human
      respiratory cells exposed to low concentrations of sodium chromate.
AB  - The mechanism of Cr(VI) genotoxicity has still not been elucidated. We used Fpg
      modified comet assay to assess direct-oxidative DNA damage on human lung (A549)
      and bronchial (BEAS-2B) cells exposed to 0.1, 0.5, 1.0 and 10 microm sodium
      chromate for 0.5, 1 and 4 h. Moreover we evaluated apoptosis by morphological
      analysis and caspase-3 activity, also after 24 h. On A549 cells a time-dependent
      DNA damage, expressed as tail DNA%, beginning from 0.5 microm was found. For
      oxidative DNA damage an induction after 30 min to 0.5 microm decreasing with
      time, and a time-dependent increase at 10 microm was found, indicating for low
      Cr(VI) concentration the oxidative stress as the first event followed by direct
      DNA damage and for the highest concentration a time-dependent increase in
      oxidative DNA damage. On BEAS-2B cells DNA damage was induced within 1 h at 0.5
      10 microm, without changes with time, showing that BEAS-2B cells are able to
      resist to Cr(VI) genotoxicity. Early oxidative DNA damage at 0.1 microm
      decreasing with time was also found. Significant apoptosis was observed by
      morphological analysis in A549 cells and to a lower extent in BEAS-2B at 10
      microm. The exposure to 10 microm induced caspase-3 activity after 4 h in BEAS-2B
      and after 24 h in A549 cells. The findings show a higher responsiveness of A549
      cells to genotoxic effect of Cr(VI) and early transient oxidative DNA damage in
      BEAS-2B. The results emphasize the suitability of this experimental model to
      evaluate the early genotoxic response of different cells to non-cytotoxic
      concentrations of Cr(VI) on target organ.

PMID- 19839026
TI  - Age-related differences in susceptibility to cisplatin-induced renal toxicity.
AB  - Limited experimental models exist to assess drug toxicity in pediatric
      populations. We recently reported how a multi-age rat model could be used for pre
      clinical studies of comparative drug toxicity in pediatric populations. The
      objective of this study was to expand the utility of this animal model, which
      previously demonstrated an age-dependent sensitivity to the classic nephrotoxic
      compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague
      Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis
      (0, 1, 3 or 6 mg kg(-1) i.p.). Urine samples were collected prior and up to 72 h
      after treatment in animals that were >or= 25 days old. Several serum, urinary and
      'omic' injury biomarkers as well as renal histopathology lesions were evaluated.
      Statistically significant changes were noted with different injury biomarkers in
      different age groups. The order of age-related Cis-induced nephrotoxicity was
      different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs
      10 >or= 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney
      injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early
      Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels
      of Kim-1 tissue mRNA and urinary protein were significantly correlated to each
      other and to the severity of renal histopathology lesions. These data indicate
      that the multi-age rat model can be used to demonstrate different age-related
      sensitivities to renal injury using mechanistically distinct nephrotoxicants,
      which is reflected in measurements of a variety of metabolite, gene transcript
      and protein biomarkers.

PMID- 19839027
TI  - Association of the metabolic syndrome with depression and anxiety in Japanese
      men: a 1-year cohort study.
AB  - BACKGROUND: Recent studies on the association between the metabolic syndrome
      (MetS) and depression have reported conflicting findings. This 1-year cohort
      study aims to evaluate the association of MetS with the development of both
      depression and anxiety. METHODS: The cohort comprised 956 Japanese male employees
      of an enterprise (mean age, 42.7 years; SD, 10.2 years). MetS was diagnosed
      according to the International Diabetes Federation criteria. The psychological
      conditions of depression and anxiety were assessed in 2 successive years by using
      the profile of mood states (POMS) questionnaire and by conducting clinical
      interviews as per the fourth edition of the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV). We evaluated the temporal and dose-response
      relationships between MetS and the development of depression and anxiety,
      controlling for potential confounding factors like age and lifestyle-related
      factors. RESULTS: We identified a positive relationship between MetS at baseline
      and new-onset depression in the subsequent year (OR 2.14, 95% CI 1.10-4.17). Of
      the five MetS components examined, only waist circumference was significantly
      related to new-onset depression (OR 2.08, 1.23-3.50). Trend analysis revealed a
      significant positive trend of association between the number of MetS components
      identified and new-onset depression (P(trend) < 0.01), but not between Mets and
      new-onset anxiety. CONCLUSIONS: Our results suggest that MetS is a predictive
      factor for the development of depression, and that waist circumference largely
      contributes to the association between MetS and depression.

PMID- 19839028
TI  - Structure characterization of lipocyclopeptide antibiotics, aspartocins A, B & C,
      by ESI-MSMS and ESI-nozzle-skimmer-MSMS.
AB  - Three lipocyclopeptide antibiotics, aspartocins A (1), B (2), and C (3), were
      obtained from the aspartocin complex by HPLC separation methodology. Their
      structures were elucidated using previously published chemical degradation
      results coupled with spectroscopic studies including ESI-MS, ESI-Nozzle Skimmer
      MSMS and NMR. All three aspartocin compounds share the same cyclic decapeptide
      core of cyclo [Dab2 (Asp1-FA)-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11].
      They differ only in the fatty acid side chain moiety (FA) corresponding to (Z)-13
      methyltetradec-3-ene-carbonyl, (+,Z)-12-methyltetradec-3-ene-carbonyl and (Z)-12
      methyltridec-3-ene-carbonyl for aspartocins A (1), B (2), and C (3),
      respectively. All of the sequence ions were observed by ESI-MSMS of the doubly
      charged parent ions. However, a number of the sequence ions observed were of low
      abundance. To fully sequence the lipocyclopeptide antibiotic structures, these
      low abundance sequence ions together with complementary sequence ions were
      confirmed by ESI-Nozzle-Skimmer-MSMS of the singly charged linear peptide parent
      fragment ions H-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-Dab2(1+)-Asp1-FA.
      Cyclization of the aspartocins was demonstrated to occur via the beta-amino group
      of Dab2 from ions of moderate intensity in the ESI-MSMS spectra. As the fatty
      acid moieties do not undergo internal fragmentations under the experimental ESI
      mass spectral conditions used, the 14 Da mass difference between the fatty acid
      moieties of aspartocins A (1) and B (2) versus aspartocin C (3) was used as an
      internal mass tag to differentiate fragment ions containing fatty acid moieties
      and those not containing the fatty acid moieties. The most numerous and abundant
      fragment ions observed in the tandem mass spectra are due to the cleavage of the
      tertiary nitrogen amide of the pipecolic acid residue-3 (16 fragment ions) and
      the proline residue-11 (7 fragment ions). In addition, the neutral loss of
      ethanimine from alpha,beta-diaminobutyric acid residue 9 was observed for the
      parent molecular ion and for 7 fragment ions.

PMID- 19839029
TI  - Methods for an improved detection of the MRI-CEST effect.
AB  - CEST imaging is a recently introduced MRI contrast modality based on the use of
      endogenous or exogenous molecules whose exchangeable proton pools transfer
      saturated magnetization to bulk water, thus creating negative contrast. One of
      the critical issues for further development of these agents is represented by
      their limited sensitivity in vivo. The aim of this work is to improve the
      detection of CEST agents by exploring new approaches through which the saturation
      transfer (ST) effect can be enhanced. The performance of the proposed methods has
      been tested in vitro and in vivo using highly sensitive and highly shifted
      lipoCEST agents, and the results were compared with the standard ST evaluation
      mode. The acquired Z-spectra were interpolated locally and voxel-by-voxel by
      smoothing splines. Besides expressing the ST in the standard mode, we explore two
      methods, enhanced and integral ST, which better exploit all the information
      contained in the Z-spectrum. By combining different modes for ST assessment a
      significant improvement in the detection of the lipoCEST agents, both in vitro
      and in vivo, has been found. The results obtained from the application of the
      proposed methods outline the importance of post-processing analysis for
      highlighting the CEST-MRI contrast.

PMID- 19839030
TI  - Ferumoxides-protamine sulfate is more effective than ferucarbotran for cell
      labeling: implications for clinically applicable cell tracking using MRI.
AB  - The use of superparamagnetic iron oxide (SPIO) for labeling cells holds great
      promise for clinically applicable cell tracking using magnetic resonance imaging.
      For clinical application, an effectively and specifically labeled cell
      preparation is highly desired (i.e. a large amount of intracellular iron and a
      negligible amount of extracellular iron). In this study we performed a direct
      comparison of two SPIO labeling strategies that have both been reported as
      efficient and clinically translatable approaches. These approaches are cell
      labeling using ferumoxides-protamine complexes or ferucarabotran particles. Cell
      labeling was performed on primary human bone marrow stromal cells (hBMSCs) and
      chondrocytes. For both cell types ferumoxides-protamine resulted in a higher
      percentage of labeled cells, a higher total iron load, a larger amount of
      intracellular iron and a lower amount of extracellular iron aggregates, compared
      with ferucarbotran. Consequently, hBMSC and chondrocyte labeling with ferumoxides
      protamine is more effective and results in more specific cell labeling than
      ferucarbotran.

PMID- 19839031
TI  - Effect of a mesitylene-based ligand cap on the relaxometric properties of Gd(III)
      hydroxypyridonate MRI contrast agents.
AB  - A series of new Gd(III) hydroxypyridonate complexes featuring a mesitylene (ME)
      derived ligand cap has been prepared. Relaxometric characterization reveals that
      the complexes tend to form large aggregates in solution with slow tumbling rates,
      as estimated from NMRD analysis, and unique pH-dependent relaxivities. The
      solution behavior and relaxometric properties are compared with those observed
      for analogous TREN-capped compounds, and the potential for use of these new ME
      capped complexes as pH-responsive MRI contrast agents is explored.

PMID- 19839032
TI  - Subclinical vascular alterations in young adults with type 1 diabetes detected by
      arterial tonometry.
AB  - BACKGROUND: Diabetes mellitus is characterized by a very high prevalence of
      atherosclerotic disease. Aims of this study were to determine arterial compliance
      parameters in type 1 diabetes (T1D) patients as an expression of early pre
      clinical endothelial dysfunction and to evaluate the impact of glucose exposure
      parameters such as the duration of diabetes and glycosylated haemoglobin
      (HbA(1c)) on the risk of developing alterations in vascular compliance. METHODS:
      23 patients with uncomplicated type 1 diabetes (mean age: 32.78 +/- 9.06 years,
      mean disease duration: 10.78 +/- 7.51 years, mean HbA(1c) levels: 7.7 +/- 1.9)
      and 26 age- and sex-matched healthy subjects (mean age: 32.3 +/- 8.51 years) were
      recruited. In these subjects, we evaluated arterial compliance by calibrated
      tonometry (HDI/Pulsewave() CR-2000). Parameters included the following: large
      artery elasticity (C1), small artery elasticity (C2), systemic vascular
      resistance (SVR) and total vascular impedance (TVI). RESULTS: Patients with
      longer duration of T1D (>10 years) showed significant alterations in C2 (4.97 +/-
      2.7 mL/mmHg x 100) and in SVR (1464.67 +/- 169.16 dina x s x cm(-5)) when
      compared with both healthy individuals (C2: 8.28 +/- 2.67 mL/mmHg x 100, p =
      0.001; SVR: 1180.58 +/- 151.55 dina x s x cm(-5), p = 0.01) and patients with
      recent-onset disease (<or=10 years) (C2: 10.02 +/- 3.6 mL/mmHg x 100, p < 0.001;
      SVR: 1124.18 +/- 178.5 dina x s x cm(-5), p < 0.000). Both disease duration and
      HbA(1c) independently predicted impaired arterial compliance. CONCLUSIONS: Young
      adult T1D patients with no signs of disease complication have detectable vessel
      wall abnormalities, particularly of small arteries, suggestive of hyperglycaemia
      related early endothelial dysfunction.

PMID- 19839034
TI  - Correlation of DTI metrics in the wall and cavity of brain abscess with histology
      and immunohistochemistry.
AB  - Diffusion tensor imaging (DTI) was performed in eight patients with brain abscess
      (BA). The aim of this study was to see the difference in the relationship between
      intercellular cell adhesion molecule-1 (ICAM-1) and lymphocyte function
      associated antigen-1 (LFA-1) expression and DTI metrics measured in vivo in the
      wall and cavity of BA and its possible explanation vis-a-vis histology and
      immunohistochemistry. Neuroinflammatory molecules (NMs) were quantified from BA
      cavity aspirate of the patients and quantitative immunohistochemical analysis was
      performed for ICAM-1 and LFA-1 in the BA wall, showing maximal positive staining
      and correlated with DTI metrics. The fractional anisotropy (FA) significantly
      increased while mean diffusivity and spherical anisotropy significantly decreased
      in the BA wall compared to the BA cavity. In the BA wall, FA and linear
      anisotropy (CL) showed a significant positive correlation with ICAM-1 and LFA-1
      expression whereas FA and planar anisotropy positively correlated with NMs
      quantified from aspirated pus respectively. Higher FA values in the BA wall
      compared to BA cavity, even when ICAM-1 and LFA-1 were expressed only in the
      macrophages and not in the collagen fibers, suggests that a combination of both
      concentric layers of collagen fibers as well as neutrophils and macrophages
      provide structural orientation and are responsible for increased FA. In the BA
      wall, increased CL was found compared to the cavity, indicating the presence of
      concentrically laid collagen fibers responsible for the diffusion of water
      molecules in the direction parallel to the collagen fibers. We conclude that in
      the BA, different mechanisms are operative for the changes in the DTI metrics in
      the wall and cavity; these conclusions are validated by histology and
      immunohistochemistry.

PMID- 19839035
TI  - Quantitative analysis of spatial proteoglycan content in articular cartilage with
      Fourier transform infrared imaging spectroscopy: Critical evaluation of analysis
      methods and specificity of the parameters.
AB  - OBJECTIVE: To evaluate the specificity of the current Fourier transform infrared
      imaging spectroscopy (FT-IRIS) methods for the determination of depthwise
      proteoglycan (PG) content in articular cartilage (AC). In addition, curve fitting
      was applied to study whether the specificity of FT-IRIS parameters for PG
      determination could be improved. METHODS: Two sample groups from the steer AC
      were prepared for the study (n = 8 samples/group). In the first group,
      chondroitinase ABC enzyme was used to degrade the PGs from the superficial
      cartilage, while the samples in the second group served as the controls. Samples
      were examined with FT-IRIS and analyzed using previously reported direct
      absorption spectrum techniques and multivariate methods and, in comparison, by
      curve fitting. Safranin O-stained sections were measured with digital
      densitometry to obtain a reference for depthwise PG distribution. RESULTS:
      Carbohydrate region-based absorption spectrum methods showed a statistically
      weaker correlation with the PG reference distributions than the results of the
      curve fitting (subpeak located approximately at 1,060 cm(-1)). Furthermore, the
      shape of the depthwise profiles obtained using the curve fitting was more similar
      to the reference profiles than with the direct absorption spectrum analysis.
      CONCLUSIONS: Results suggest that the current FT-IRIS methods for PG analysis
      lack the specificity for quantitative measurement of PGs in AC. The curve fitting
      approach demonstrated that it is possible to improve the specificity of the PG
      analysis. However, the findings of the present study suggest that further
      development of the FT-IRIS analysis techniques is still needed.

PMID- 19839036
TI  - Chemical and morphological features of dental composite resin: influence of light
      curing units and immersion media.
AB  - AIMS: The study evaluated the influence of light curing units and immersion media
      on superficial morphology and chemistry of the nanofilled composite resin Supreme
      XT (3M) through the EDX analysis and SEM evaluation. Light curing units with
      different power densities and mode of application used were XL 3000 (480
      mW/cm(2)), Jet Lite 4000 Plus (1230mW/cm(2)), and Ultralume Led 5 (790 mW/cm(2))
      and immersion media were artificial saliva, Coke((R)), tea and coffee, totaling
      12 experimental groups. Specimens (10 mm x 2 mm) were immersed in each respective
      solution for 5 min, three times a day, during 60 days and stored in artificial
      saliva at 37 degrees C +/- 1 degrees C between immersion periods. Topography and
      chemical analysis was qualitative. FINDINGS: Groups immersed in artificial
      saliva, showed homogeneous degradation of matrix and deposition of calcium at the
      material surface. Regarding coffee, there was a reasonable chemical degradation
      with loss of load particles and deposition of ions. For tea, superficial
      degradation occurred in specific areas with deposition of calcium, carbon,
      potassium and phosphorus. For Coke((R)), excessive matrix degradation and loss of
      load particles with deposition of calcium, sodium, and potassium. CONCLUSION:
      Light curing units did not influence the superficial morphology of composite
      resin tested, but the immersion beverages did. Coke((R)) affected material's
      surface more than did the other tested drinks.

PMID- 19839037
TI  - Satoyoshi syndrome with unusual skeletal abnormalities and parental
      consanguinity.
AB  - Satoyoshi syndrome (SS) (OMIM 600705) is a rare multisystemic disorder of unknown
      etiology characterized by progressive painful intermittent muscle spasm, alopecia
      universalis, diarrhea, short stature, amenorrhea, and secondary skeletal
      abnormalities mimicking a metaphyseal chondrodysplasia. To date all reported
      cases have been sporadic. We describe a 26-year-old Mexican woman, a product of
      consanguineous parents with clinical characteristics of SS. Our patient, also
      showed skeletal anomalies not previously reported that seems to be a coincidental
      finding.

PMID- 19839038
TI  - Weismann-Netter syndrome and mental retardation: a new patient and review of the
      literature.
AB  - In 1954, Weismann-Netter and Stuhl described three sporadic adults and a mother
      and her three children with short stature and congenital anterior bowing of lower
      legs [Weismann-Netter and Stuhl (1954); Presse Med 62:1618-1622]. They named the
      condition "toxopachyosteose diaphysaire tibio-peroniere," which presently is
      known as Weismann-Netter syndrome (WNS) (OMIM 112350). Since then more than 100
      patients have been published. Nearly all have been case reports in French medical
      literature, and the first report in the Anglo-American literature appeared in
      1988. Only a minority of the publications have appeared during the past two
      decades. The diagnostic findings of WNS are anterior bowing of the diaphyses of
      tibia and fibula, broadening or "tibialization" of the fibula and posterior
      cortical thickening of the two bones. Also the diaphyses of other long bones may
      be similarly affected but usually to a milder degree. The cause of the condition
      is unknown, but frequent familial cases suggest a genetic defect with autosomal
      dominant inheritance. Several of the WNS patients have also had mental
      retardation (MR), but the existence of a WNS-MR syndrome is still pending. We
      describe a sporadic patient with typical WNS skeletal findings and MR. He also
      had postnatal growth deceleration with partially corrective pubertal growth,
      normal head size and normal brain structures on MRI. We review the WNS
      literature.

PMID- 19839039
TI  - Replication of novel susceptibility locus for nonsyndromic cleft lip with or
      without cleft palate on chromosome 8q24 in Estonian and Lithuanian patients.

PMID- 19839040
TI  - Pulmonary hypoplasia-diaphragmatic hernia-anophthalmia-cardiac defect (PDAC)
      syndrome due to STRA6 mutations--what are the minimal criteria?
AB  - Microphthalmic syndrome 9 (OMIM601186) is a genetically and phenotypically
      variable condition, comprising anophthalmia, pulmonary hypoplasia, diaphragmatic
      hernia, and cardiac malformations (PDAC syndrome). Reported cases have all been
      associated with fetal/neonatal death or developmental delay. Recessive stimulated
      by retinoic acid gene 6 homolog (STRA6) mutations have recently been identified
      as the cause of cases of PDAC in which distinct, "bushy" eyebrows have been
      observed. We describe a patient with clinical anophthalmia, bushy eyebrows,
      patent ductus arteriosus, and normal development at age 30 months, who is a
      compound heterozygote for two novel STRA6 missense mutations. This patient's
      phenotype is consistent with the multisystemic malformations of PDAC syndrome,
      but is somewhat milder. This is the first living patient with compound
      heterozygous STRA6 mutations, which may explain her milder phenotype. We conclude
      that STRA6 analysis should be considered in all patients with clinical
      anophthalmia. Genetic counseling should be cautious with respect to long-term
      developmental outcomes.

PMID- 19839041
TI  - X-linked brachytelephalangic chondrodysplasia punctata: a simple trait that is
      not so simple.
AB  - Brachytelephalangic chondrodysplasia punctata (CDPX1) is an X-linked recessive
      disorder caused by mutations in the arylsulfatase E (ARSE) gene, characterized by
      the presence of stippled epiphyses on radiograms in infancy and early childhood.
      Other features include hypoplasia of the midface and of the nasal bone, short
      stature, brachytelephalangy, and ectopic calcifications. Patients display marked
      clinical variability and there is no clear genotype-phenotype correlation. We
      report on a 14-month-old boy who presented with respiratory stridor due to
      tracheal calcifications. He had mild midface hypoplasia and brachytelephalangy,
      but lacked other features of CDPX1, such as short stature and epiphyseal
      stippling. Analysis of ARSE detected a deletion involving exons 7-10. His
      maternal grandfather harbored the same defect but lacked any clinical
      manifestation. These findings underscore two important points. First, the absence
      of stippled epiphyses on radiograms should not be considered an exclusion
      criteria for ARSE mutation screening in patients with other features of the
      disease, especially after the neonatal period. Second, counseling to parents of
      affected children should be cautious because although the theoretical risk of
      inheriting the ARSE mutation is 50% for every male child of a carrier mother, it
      is not possible to determine whether he will develop features of CDPX1 and the
      eventual severity of symptoms. The actual risk of developing the disease is
      probably lower than 50%. Conversely, normal prenatal sonography does not rule out
      potentially severe complications such as tracheal stenosis.

PMID- 19839042
TI  - Calvarial doughnut lesions and osteoporosis: a new three-generation family and
      review.
AB  - Familial calvarial doughnut lesions (CDLs; OMIM 126550) is a rare autosomal
      dominant low bone density disorder characterized by distinctive X-ray
      translucencies of the skull, multiple fractures, elevated serum alkaline
      phosphatase, and dental caries. Only three families comprising 22 cases and 29
      sporadic cases with the disorder have been reported. We describe a three
      generation family consisting of three cases with clinical, radiological,
      biochemical, and histological findings consistent with this condition. All
      affected family members presented with childhood onset primary osteoporosis and
      typical CDLs or hyperostosis of the skull. In addition, the youngest family
      member was diagnosed with congenital glaucoma and her paternal grandmother with
      chronic congestive glaucoma. Glaucoma has not been previously described in this
      disorder. Adult patients also had recurrent cranial nerve palsies. No pathogenic
      mutations in the genes encoding low density lipoprotein receptor-related protein
      5 (LRP5) or type I collagen (COL1A1 or COL1A2) were identified, suggesting that
      the disorder is caused by another dominant, yet unidentified gene. The literature
      is reviewed.

PMID- 19839043
TI  - De novo terminal 22q12.3q13.3 duplication with pituitary hypoplasia.

PMID- 19839044
TI  - Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome
      previously diagnosed as Seckel syndrome: report of a novel mutation of the PCNT
      gene.
AB  - We report on a 3-year-old boy with prenatal onset of proportionate dwarfism,
      postnatal severe microcephaly, high forehead with receded hairline, sparse scalp
      hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel
      syndrome. At age 3 years, he became paralyzed due to a cerebrovascular
      malformation. Based on the clinical and radiological features showing evidence of
      skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic
      primordial dwarfism type II (MOPD II) syndrome. Western blot analysis of the
      patient's lymphoblastoid cell line lysate showed the absence of the protein
      pericentrin. Subsequent molecular analysis identified a novel homozygous single
      base insertion (c.1527_1528insA) in exon 10 of the PCNT gene, which leads to a
      frameshift (Treo510fs) and to premature protein truncation. PCNT mutations must
      be considered diagnostic of MOPD II syndrome. A possible role of pericentrin in
      the development of cerebral vessels is suggested.

PMID- 19839045
TI  - Maternal attitudes toward DNA collection for gene-environment studies: a
      qualitative research study.
AB  - To assess attitudes toward DNA collection in an epidemiological study, focus
      groups were assembled in September 2007 with mothers who had participated in a
      case-control study of birth defects. Each recruited mother previously had
      completed an interview and had received a mailed kit containing cytobrushes to
      collect buccal cells for DNA from herself, her infant, and her infant's father
      during the period July 2004 through July 2007. A total of 38 mothers attended six
      focus groups comprising: (1) non-Hispanic Black mothers of case infants who
      participated or (2) did not participate in DNA collection, (3) mothers of any
      race or ethnicity who had case infants of low birth weight who participated or
      (4) did not participate in DNA collection, and (5) non-Hispanic Black mothers of
      control infants who participated or (6) did not participate in DNA collection.
      Moderator-led discussions probed maternal attitudes toward providing specimens,
      factors that influenced decision making, and collection method preferences.
      Biologics participants reported that they provided DNA for altruistic reasons.
      Biologics nonparticipants voiced concerns about government involvement and how
      their DNA will be used. Information provided (or not provided) on DNA use,
      storage, and disposal influenced decision making. Biologics participants and
      nonparticipants reported that paternal skepticism was a barrier to participation.
      All mothers were asked to rank DNA collection methods in terms of preference
      (cytobrushes, saliva, mouthwash, newborn blood spots, and blood collection).
      Preferred methods were convenient and noninvasive. Better understanding attitudes
      toward DNA collection and preferred collection methods might allow more inclusive
      participation and benefit future studies.

PMID- 19839046
TI  - Genomic alterations in histopathologically normal breast tissue from BRCA1
      mutation carriers may be caused by BRCA1 haploinsufficiency.
AB  - Multiple biopsies of normal breast tissue from 10 BRCA1 mutation carriers have
      been analyzed using array-based comparative genomic hybridization. Normal breast
      tissue from five age-matched control subjects without a family history of breast
      cancer was included for reference purposes. We repeatedly found multiple low copy
      number aberrations at a significantly higher frequency in histopathologically
      normal tissue from BRCA1 mutation carriers than in normal control tissue. Some of
      these aberrations were similar across samples from different patients and linked
      to biological functions such as transcriptional regulation and DNA binding. We
      also observed a high degree of genomic heterogeneity between samples from the
      same patient, suggestive of tissue heterogeneity and etiological clonality in the
      breast epithelium. We show that neither loss of heterozygosity nor promoter
      methylation of the wild-type BRCA1 allele is the predominant mechanistic origin
      of the observed genomic instability. Instead, we propose that haploinsufficiency
      of BRCA1 might be the underlying cause responsible for initiation of breast
      cancer in these predisposed women, making cells vulnerable to mitotic
      recombination. We also propose that loss of ERalpha expression is preceded by
      genetic instability in the initiation of BRCA1-dependent tumorigenesis,
      indicating that the breast epithelium of BRCA1 mutation carriers may initially be
      estrogen-responsive. Our results imply that genomic instability instigated by
      BRCA1 haploinsufficiency may be required for breast cancer initiation in BRCA1
      mutation carriers. Finding molecular markers of tumor initiation and progression,
      for the potential use in early disease detection, may be of great clinical
      importance for the improved management of at-risk women.

PMID- 19839047
TI  - Metal is not inert: role of metal ions released by biocorrosion in aseptic
      loosening--current concepts.
AB  - Metal implants are essential therapeutic tools for the treatment of bone
      fractures and joint replacements. The metals and metal alloys used in
      contemporary orthopedic and trauma surgery are well tolerated by the majority of
      patients. However, complications resulting from inflammatory and immune reactions
      to metal implants have been well documented. This review briefly discusses the
      different mechanisms of metal implant corrosion in the human body, which lead to
      the release of significant levels of metal ions into the peri-implant tissues and
      the systemic blood circulation. Additionally, this article reviews the effects of
      the released ions on bone metabolism and the immune system and discusses their
      involvement in the pathophysiological mechanisms of aseptic loosening and metal
      hypersensitivity in patients with metal implants.

PMID- 19839048
TI  - Involvement of prostaglandins and histamine in nickel wire-induced acute
      inflammation in mice.
AB  - The irritancy of Nickel (Ni) ions has been well documented clinically. However,
      the chemical mediators involved in the acute inflammation induced by solid Ni are
      not fully understood. We used the Ni wire-implantation model in mice and examined
      roles of prostaglandins and histamine in plasma leakage in the acute phase. The
      subcutaneous implantation of a Ni wire into the back of mice induced plasma
      leakage from 8 to 24 h and tissue necrosis around the wire at 3 days, whereas the
      implantation of an aluminum wire induced no such inflammatory responses. An
      increase in the mRNA for cyclooxygenase (COX)-2 and HDC in cells around the Ni
      wire was detected 4 h after the implantation. The leakage of plasma at 8 h was
      inhibited by indomethacin in a dose-dependent manner. Dexamethasone and the p38
      MAP kinase inhibitor SB203580 also inhibited the exudation of plasma consistent
      with the inhibition of the expression of COX-2 mRNA. Furthermore, plasma leakage
      was partially but siginificantly reduced in histamine H1 receptor knockout mice
      and histidine decarboxylase (HDC) knockout mice but not in H2 receptor knockout
      mice. These results suggested that the Ni ions released from the wire induced the
      expression of COX-2 and HDC, resulting in an increase in vascular permeability
      during the acute phase of inflammation.

PMID- 19839049
TI  - E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family
      alterations is related to mesenchymal and drug-resistant phenotypes in human
      breast cancer cells.
AB  - The conversion of early stage tumors into invasive malignancies with an
      aggressive phenotype has been associated with the irreversible loss of E-cadherin
      expression. The loss of E-cadherin expression in human tumors, including breast
      cancer, has been attributed to promoter CpG island hypermethylation and direct
      inhibition by transcriptional repressors. Recent evidence demonstrates that up
      regulation of E-cadherin by microRNA-200b (miR-200b) and miR-200c through direct
      targeting of transcriptional repressors of E-cadherin, ZEB1, and ZEB2, inhibits
      epithelial-to-mesenchymal transition (EMT), a crucial process in the tumor
      progression. We demonstrate that microRNA miR-200 family-mediated transcriptional
      up-regulation of E-cadherin in mesenchymal MDA-MB-231 and BT-549 cells is
      associated directly with translational repression of ZEB1 and indirectly with
      increased acetylation of histone H3 at the E-cadherin promoter. The increase in
      histone H3 acetylation may be attributed to the disruption of repressive
      complexes between ZEB1 and histone deacetylases and to the inhibition of SIRT1, a
      class III histone deacetylase. These events inhibit EMT and reactivate a less
      aggressive epithelial phenotype in cancer cells. Additionally, disruption of ZEB1
      histone deacetylase repressor complexes and down-regulation of SIRT1 histone
      deacetylase up-regulate proapoptotic genes in the p53 apoptotic pathway resulting
      in the increased sensitivity of cancer cells to the chemotherapeutic agent
      doxorubicin.

PMID- 19839050
TI  - Tonsillitis, tonsillectomy and Hodgkin's lymphoma.
AB  - It has been debated whether the reported increased risk of Hodgkin's lymphoma
      (HL) after tonsillectomy could be due to some underlying factor rather than the
      surgery itself. We studied whether not only tonsillectomy but also tonsillitis
      was associated with HL. This nationwide cohort study included all Danish
      residents during 1977-2001. Information on a diagnosis of tonsillitis,
      tonsillectomy, or HL was obtained from national registries. During 124 million
      person-years we observed 2,988 HL patients of whom 58 were tonsillectomized (most
      with preceding tonsillitis) and 14 were diagnosed with only tonsillitis at more
      than 1 year before HL diagnosis. Tonsillectomy was associated with a
      significantly increased HL risk in persons under 15 years of age as follows: 1-4
      years after tonsillectomy, relative risk (RR) = 3.9 [95% CI: 1.4-11; n = 4]; >5
      years after tonsillectomy, RR = 3.5 [1.4-8.5; n = 5]. No young cases of HL
      occurred among persons diagnosed with only tonsillitis. In contrast, 1-4 years
      after a hospital diagnosis of tonsillitis without subsequent tonsillectomy we
      found an increased HL risk in persons aged 15 years or above as follows: 15-34
      years of age at HL diagnosis, RR = 3.5 [1.6-7.7; n = 6]; 35+ years, RR = 5.9 [2.2
      16; n = 4]. Age at tonsillitis or tonsillectomy did not modify HL risk within the
      3 age strata. An increased HL risk was found both after tonsillectomy and after
      an isolated diagnosis of tonsillitis. These results suggest that tonsillitis is a
      risk factor for HL and not that, as previously reported, only the surgical
      removal of tonsils is a risk factor.

PMID- 19839051
TI  - Breath gas aldehydes as biomarkers of lung cancer.
AB  - There is experimental evidence that volatile substances in human breath can
      reflect presence of neoplasma. Volatile aldehydes were determined in exhaled
      breath of 12 lung cancer patients, 12 smokers and 12 healthy volunteers. Alveolar
      breath samples were collected under control of expired CO(2). Reactive aldehydes
      were transformed into stable oximes by means of on-fiber-derivatization (SPME
      OFD). Aldehyde concentrations in the ppt and ppb level were determined by means
      of gas chromatography-mass spectrometry (GC-MS). Exhaled concentrations were
      corrected for inspired values. Exhaled C(1)-C(10) aldehydes could be detected in
      all healthy volunteers, smokers and lung cancer patients. Concentrations ranged
      from 7 pmol/l (161 pptV) for butanal to 71 nmol/l (1,582 ppbV) for formaldehyde.
      Highest inspired concentrations were found for formaldehyde and acetaldehyde (0
      55 nmol/l and 0-13 nmol/l, respectively). Acetaldehyde, propanal, butanal,
      heptanal and decanal concentrations showed no significant differences for cancer
      patients, smokers and healthy volunteers. Exhaled pentanal, hexanal, octanal and
      nonanal concentrations were significantly higher in lung cancer patients than in
      smokers and healthy controls (p(pentanal) = 0.001; p(hexanal) = 0.006; p(octanal)
      = 0.014; p(nonanal) = 0.025). Sensitivity and specificity of this method were
      comparable to the diagnostic certitude of conventional serum markers and CT
      imaging. Lung cancer patients could be identified by means of exhaled pentanal,
      hexanal, octanal and nonanal concentrations. Exhaled aldehydes reflect aspects of
      oxidative stress and tumor-specific tissue composition and metabolism.
      Noninvasive recognition of lung malignancies may be realized if analytical
      skills, biochemical knowledge and medical expertise are combined into a joint
      effort.

PMID- 19839052
TI  - Amplicons on chromosome 12q13-21 in glioblastoma recurrences.
AB  - There is limited knowledge on the in vivo behavior of amplified regions in human
      tumors. First evidence indicates that amplicon structures are largely maintained
      in recurrent tumors. Here, we investigated the fate of amplified regions in
      several independent cases of recurrent glioblastoma and the possible association
      of 12q13-21 amplifications and survival. We analyzed 12q13-21 amplicon numbers
      and sizes in glioblastoma and their recurrences by array-CGH. The majority of the
      12q13-21 amplicons found in the original tumor are lost in the subsequent
      recurrence. Likewise, the majority of the amplicons found in the first recurrence
      are lost in the second recurrence. The remaining amplicons of recurrences often
      expanded or were maintained in size. Because of re-emergences and de novo
      appearances of amplicons, however, the overall number of amplicons did not
      decrease in the recurrences. Understanding genetic changes including gene
      amplifications in the development of tumor recurrences will contribute to
      rational therapeutic strategies for an improved patient survival. We recognized a
      significant longer survival time in glioblastoma patients that lack
      amplifications of either CDK4, CYP27B1, XRCC6BP1 (KUB3), or MDM2.

PMID- 19839053
TI  - Maternal folate and other vitamin supplementation during pregnancy and risk of
      acute lymphoblastic leukemia in the offspring.
AB  - The Australian Study of Causes of Acute Lymphoblastic Leukemia in Children (Aus
      ALL) was designed to test the hypothesis, raised by a previous Western Australian
      study, that maternal folic acid supplementation during pregnancy might reduce the
      risk of childhood acute lymphoblastic leukemia (ALL). Aus-ALL was a national,
      population-based, multicenter case-control study that prospectively recruited 416
      cases and 1,361 controls between 2003 and 2007. Detailed information was
      collected about maternal use of folic acid and other vitamin supplements before
      and during the index pregnancy. Data were analyzed using logistic regression,
      adjusting for matching factors and potential confounders. A meta-analysis with
      the results of previous studies of folic acid supplementation was also conducted.
      We found weak evidence of a protective effect of maternal folate supplementation
      before pregnancy against risk of childhood ALL, but no evidence for a protective
      effect of its use during pregnancy. A meta-analysis including this and 2 other
      studies, but not the study that raised the hypothesis, also found little evidence
      that folate supplementation during pregnancy protects against ALL: the summary
      odds ratios (ORs) for folate supplementation were 1.06 [95% confidence interval
      (CI): 0.77-1.48] with reference to no folate supplementation and 1.02 (95% CI:
      0.86-1.20) with reference to no vitamin supplementation. For vitamin
      supplementation in general, the summary OR from a meta-analysis of 5 studies
      including Aus-ALL-was 0.83 (95% CI: 0.73-0.94). Vitamin supplementation in
      pregnancy may protect against childhood ALL, but this effect is unlikely to be
      large or, if real, specifically due to folate.

PMID- 19839054
TI  - Nuclear receptors in head and neck cancer: current knowledge and perspectives.
AB  - Disease management of head and neck cancer has improved significantly. However, a
      high rate of early recurrences and metastasis still counteract improvement of
      long-term survival. Hence, the quest for molecular mechanisms and key regulatory
      factors exploitable by targeted therapies is still ongoing. Such potential
      candidates may include also nuclear receptors, belonging to a superfamily of
      transcription factors implicated in a broad spectrum of physiological and
      pathophysiological processes. As dysfunction of nuclear receptor signaling
      contributes to a variety of proliferative diseases, they are major targets for
      drug discovery and hold promising potential for the development of improved
      anticancer treatment strategies. Several nuclear receptors have also been
      associated with head and neck cancer, and strategies targeting these molecules
      are currently tested in clinical trials. However, reports and molecular knowledge
      on the pathobiological relevance of nuclear receptors for cancers of the head and
      neck is currently rather fragmented. Hence, this review provides a general
      overview of nuclear receptors' molecular functions and summarizes their potential
      prognostic and therapeutic relevance for this tumor entity.

PMID- 19839055
TI  - Generation of human-induced pluripotent stem cells in the absence of exogenous
      Sox2.
AB  - Induced pluripotent stem cell technology has attracted enormous interest for
      potential application in regenerative medicine. Here, we report that a specific
      glycogen synthase kinase 3 (GSK-3) inhibitor, CHIR99021, can induce the
      reprogramming of mouse embryonic fibroblasts transduced by only two factors, Oct4
      and Klf4. When combined with Parnate (also named tranylcypromine), an inhibitor
      of lysine-specific demethylase 1, CHIR99021 can cause the reprogramming of human
      primary keratinocyte transduced with the two factors, Oct4 and Klf4. To our
      knowledge, this is the first time that human iPS cells have been generated from
      somatic cells without exogenous Sox2 expression. Our studies suggest that the GSK
      3 inhibitor might have a general application to replace transcription factors in
      both mouse and human reprogramming.

PMID- 19839058
TI  - Literature review: gastrointestinal symptoms in ASD, brain structure of identical
      twins with ASD.

PMID- 19839057
TI  - Physical activity and exercise dependence during inpatient treatment of
      longstanding eating disorders: an exploratory study of excessive and non
      excessive exercisers.
AB  - OBJECTIVE: To describe changes in physical activity (PA) and exercise dependence
      score during treatment of eating disorders (ED), and to explore correlations
      among changes in PA, exercise motivation, exercise dependence score and ED
      psychopathology in excessive and non-excessive exercisers. METHOD: Thirty-eight
      adult females receiving inpatient treatment for anorexia nervosa, bulimia nervosa
      or ED not otherwise specified participated in this prospective study. Assessments
      included accelerometer assessed PA, Exercise Dependence Scale, Reasons for
      Exercise Inventory, ED Examination, and ED Inventory. RESULTS: Amount of PA was
      significantly reduced in non-excessive exercisers during treatment, in excessive
      exercisers there was a trend towards reduced amount of PA from admission to
      discharge. In excessive exercisers, reduced ED psychopathology was correlated
      with reduction in exercise dependence score and perceived importance of exercise
      to regulate negative affects, but not with importance of exercise for
      weight/appearance. These associations were not found in non-excessive exercisers.
      DISCUSSION: Excessive exercise is an important issue in longstanding ED, and the
      excessive exercising patients need help to develop alternative strategies to
      regulate negative affects.

PMID- 19839056
TI  - Requirement of alpha(4)beta(1) and alpha(5)beta(1) integrin expression in bone
      marrow-derived progenitor cells in preventing endotoxin-induced lung vascular
      injury and edema in mice.
AB  - The goal of this study was to determine the role of integrin-mediated adhesion of
      bone-marrow-derived progenitor cells (BMPCs) as a requirement for the endothelial
      barrier protection in a lung injury model. C57BL mice were used as the source for
      BMPCs, which were characterized as CD34(+) and fetal liver kinase-1 (Flk1)(+) and
      also an expression of a repertoire of integrins. We used a mouse model of
      bacterial lipopolysaccharide (LPS)-induced lung vascular injury and edema
      formation to test the effects of BMPC integrin expression in preventing
      endothelial barrier injury. Adhesion of BMPCs to purified extracellular matrix
      proteins induced focal adhesion kinase (Fak) phosphorylation and formation of
      branching point structures in a alpha(4) and alpha(5) integrin-dependent manner.
      BMPCs expressing red fluorescent protein (RFP) were administered via the retro
      orbital venous route in mice treated intraperitonially with LPS (7.5 mg/kg body
      weight). We observed increased retention of RFP-labeled Flk1(+) and CD34(+) BMPCs
      for up to 8 weeks in mice injured with LPS. BMPC transplantation increased
      survival by 50% (at 72-96 hours after LPS) and reduced lung vascular injury and
      extravascular water content induced by LPS. However, blocking with anti-alpha(4)
      or anti-alpha(5) integrin antibody or shRNA-mediated silencing of alpha(4) or
      alpha(5) integrins in donor BMPCs failed to prevent the vascular injury or edema
      formation and mortality. Thus, alpha(4) and alpha(5) integrin-dependent adhesion
      of BMPCs in lung tissue plays a critical role in preventing lung vascular injury
      and increasing survival in a mouse model of LPS-induced acute lung injury.

PMID- 19839059
TI  - Development and neuronal dependence of cutaneous sensory nerve formations:
      Lessons from neurotrophins.
AB  - Null mutations of genes from the NGF family of NTs and their receptors (NTRs)
      lead to loss/reduction of specific neurons in sensory ganglia; conversely,
      cutaneous overexpression of NTs results in skin hyperinnervation and increase or
      no changes in the number of sensory neurons innervating the skin. These neuronal
      changes are paralleled with loss of specific types of sensory nerve formations in
      the skin. Therefore, mice carrying mutations in NT or NTR genes represent an
      ideal model to identify the neuronal dependence of each type of cutaneous sensory
      nerve ending from a concrete subtype of sensory neuron, since the development,
      maintenance, and structural integrity of sensory nerve formations depend upon
      sensory neurons. Results obtained from these mouse strains suggest that TrkA
      positive neurons are connected to intraepithelial nerve fibers and other sensory
      nerve formations depending from C and Adelta nerve fibers; the neurons expressing
      TrkB and responding to BDNF and NT-4 innervate Meissner corpuscles, a
      subpopulation of Merkell cells, some mechanoreceptors of the piloneural complex,
      and the Ruffini's corpuscles; finally, a subpopulation of neurons, which are
      responsive to NT-3, support postnatal survival of some intraepithelial nerve
      fibers and Merkel cells in addition to the muscle mechanoreceptors. On the other
      hand, changes in NTs and NTRs affect the structure of non-nervous structures of
      the skin and are at the basis of several cutaneous pathologies. This review is an
      update about the role of NTs and NTRs in the maintenance of normal cutaneous
      innervation and maintenance of skin integrity.

PMID- 19839060
TI  - Ultrastructural alterations in liver of mice exposed chronically and
      transgenerationally to aqueous extract of betel nut: Implications in betel nut
      induced carcinogenesis.
AB  - The aqueous extract of betel nut (AEBN) induces the formation of preneoplastic
      nodules in the liver of Swiss Albino mice and leads to increased predisposition
      to cancer when administered transgenerationally. The aim of this investigation
      was to elucidate the alterations in ultrastructure of subcellular organelles in
      the liver nodules using transmission electron microscopy and to determine whether
      these alterations have implications in AEBN-induced carcinogenesis. Male and
      female Swiss Albino mice were exposed to AEBN chronically and transgenerationally
      at a dose of 2 mg/mL in drinking water for 24 weeks. Extensive polymorphism was
      noted in nuclear shape and heterochromatin organization. Heterochromatin
      aggregation and marginalization were observed in the nuclei of chronically
      exposed mice, whereas transgenerationally exposed mice exhibited dispersion or
      loss of heterochromatin. The nuclear envelope was disrupted, and the nucleoli
      were enlarged in chronically exposed mice, whereas in transgenerationally exposed
      mice the nucleoli were reduced in size or totally absent. The cisternae of the
      rough endoplasmic reticulum were dilated and disrupted, and a large number of
      autophagic vesicles were observed in both chronically and transgenerationally
      exposed mice. Atypical mitochondria that underwent extensive cristolysis and
      progressively declined in size and number from the chronically exposed mice to
      the different generations of transgenerationally exposed mice were also observed.
      Thus, exposure to AEBN resulted in severe loss of ultrastructural integrity of
      cells in the liver nodules, and the progressive loss of mitochondrial function
      appeared to play a significant role in increasing the predisposition to cancer of
      mice exposed transgenerationally to AEBN.

PMID- 19839061
TI  - Cost-effectiveness of nationwide hepatitis B catch-up vaccination among children
      and adolescents in China.
AB  - Liver disease and liver cancer associated with childhood-acquired chronic
      hepatitis B are leading causes of death among adults in China. Despite expanded
      newborn hepatitis B vaccination programs, approximately 20% of children under age
      5 years and 40% of children aged 5 to 19 years remain unprotected from hepatitis
      B. Although immunizing them will be beneficial, no studies have examined the cost
      effectiveness of hepatitis B catch-up vaccination in an endemic country like
      China. We examined the cost-effectiveness of a hypothetical nationwide free
      hepatitis B catch-up vaccination program in China for unvaccinated children and
      adolescents aged 1 to 19 years. We used a Markov model for disease progression
      and infections. Cost variables were based on data published by the Chinese
      Ministry of Health, peer-reviewed Chinese and English publications, and the GAVI
      Alliance. We measured costs (2008 U.S. dollars and Chinese renminbi), quality
      adjusted life years, and incremental cost-effectiveness from a societal
      perspective. Our results show that hepatitis B catch-up vaccination for children
      and adolescents in China is cost-saving across a range of parameters, even for
      adolescents aged 15 to 19 years old. We estimate that if all 150 million
      susceptible children under 19 were vaccinated, more than 8 million infections and
      65,000 deaths due to hepatitis B would be prevented. CONCLUSION: The adoption of
      a nationwide free catch-up hepatitis B vaccination program for unvaccinated
      children and adolescents in China, in addition to ongoing efforts to improve
      birth dose and newborn vaccination coverage, will be cost-saving and can generate
      significant population-wide health benefits. The success of such a program in
      China could serve as a model for other endemic countries.

PMID- 19839062
TI  - BH3-only protein bid participates in the Bcl-2 network in healthy liver cells.
AB  - Bcl-2 homology domain 3 (BH3)-only protein Bid is posttranslationally cleaved by
      caspase-8 into its truncated form (tBid) and couples with stress signals to the
      mitochondrial cell death pathway. However, the physiological relevance of Bid is
      not clearly understood. Hepatocyte-specific knockout (KO) of Bcl-xL leads to
      naturally-occurring apoptosis despite co-expression of Mcl-1, which shares a
      similar anti-apoptotic function. We generated Bcl-xL KO, Bcl-xL/Bid double KO,
      Bcl-xL/Bak double KO, Bcl-xL/Bax double KO, and Bcl-xL/Bak/Bax triple KO mice and
      found that hepatocyte apoptosis caused by Bcl-xL deficiency was completely
      dependent on Bak and Bax, and surprisingly on Bid. This indicated that, in the
      absence of Bid, Bcl-xL is not required for the integrity of differentiated
      hepatocytes, suggesting a complicated interaction between core Bcl-2 family
      proteins and BH3-only proteins even in a physiological setting. Indeed, a small
      but significant level of tBid was present in wild-type liver under physiological
      conditions. tBid was capable of binding to Bcl-xL and displacing Bak and Bax from
      Bcl-xL, leading to release of cytochrome c from wild-type mitochondria. Bcl-xL
      deficient mitochondria were more susceptible to tBid-induced cytochrome c
      release. Finally, administration of ABT-737, a pharmacological inhibitor of Bcl
      2/Bcl-xL, caused Bak/Bax-dependent liver injury, but this was clearly ameliorated
      with a Bid KO background. CONCLUSION: Bid, originally considered to be a sensor
      for apoptotic stimuli, is constitutively active in healthy liver cells and is
      involved in the Bak/Bax-dependent mitochondrial cell death pathway. Healthy liver
      cells are addicted to a single Bcl-2-like molecule because of BH3 stresses, and
      therefore special caution may be required for the use of the Bcl-2 inhibitor for
      cancer therapy.

PMID- 19839063
TI  - Liver stiffness identifies two different patterns of fibrosis progression in
      patients with hepatitis C virus recurrence after liver transplantation.
AB  - Significant liver fibrosis (F >or= 2) and portal hypertension (hepatic venous
      pressure gradient [HVPG] >or= 6 mmHg) at 1 year after liver transplantation (LT)
      identify patients with severe hepatitis C recurrence. We evaluated whether
      repeated liver stiffness measurements (LSM) following LT can discriminate between
      slow and rapid "fibrosers" (fibrosis stage F2-F4 at 1 year after LT). Eighty-four
      patients who had undergone LT and who were infected with hepatitis C virus (HCV)
      and 19 LT controls who were not infected with HCV underwent LSM at 3, 6, 9, and
      12 months after LT. All HCV-infected patients underwent liver biopsy 12 months
      after LT (paired HVPG measurements in 74); 31 (37%) were rapid fibrosers. Median
      LSM (in kilopascal) at months 6, 9, and 12 were significantly higher in rapid
      fibrosers (9.9, 9.5, 12.1) than in slow fibrosers (6.9, 7.5, 6.6) (P < 0.01 all
      time points). The slope of liver stiffness progression (kPa x month) in rapid
      fibrosers (0.42) was significantly greater than in slow fibrosers (0.05) (P <
      0.001), suggesting two different speeds of liver fibrosis progression. Figures
      were almost identical for patients with HVPG >or= 6 mmHg or HVPG < 6 mmHg at 1
      year after LT. Multivariate analysis identified donor age, bilirubin level, and
      LSM as independent predictors of fibrosis progression and portal hypertension in
      the estimation group (n = 50) and were validated in a second group of 34
      patients. The areas under the receiver operating characteristic curve that could
      identify rapid fibrosers and patients with portal hypertension as early as 6
      months after LT were 0.83 and 0.87, respectively, in the estimation group and
      0.75 and 0.80, respectively, in the validation group. CONCLUSION: Early and
      repeated LSM following hepatitis C recurrence in combination with clinical
      variables discriminates between rapid and slow fibrosers after LT.

PMID- 19839065
TI  - Uniform format for disclosure of competing interests in ICMJE Journals.

PMID- 19839066
TI  - Reference pricing system and competition: case study from Portugal.
AB  - AIM: To characterize the patterns of competition for a sample of drugs in the
      Portuguese pharmaceutical market before (January 2002-March 2003) and after
      (April 2003-June 2003) the introduction of the reference pricing system (RPS).
      METHODS: We performed a descriptive, retrospective, longitudinal analysis, with
      monthly observations from January 2002 until June 2003 of 15 homogeneous groups.
      The groups represented the upper limit of public pharmaceutical expenditure in
      the RPS segment in 2003 (n=270). Measures of competition were: 1) number of
      presentations; 2) prescriptions' concentration in the generic and originator
      (brand) segments, using Herfindahl-Hirschman Index (HHI); and 3) dominant
      positions of market leader in the homogeneous group. A correlation analysis
      between the number of presentations, the HHI, and the dominant position of the
      market leader was performed using Pearson coefficient of correlation. RESULTS:
      The structure of the market changed with the introduction of RPS. We found an
      increasing number of generic presentations (from 4+/-3 to 7+/-4; mean+/-standard
      deviation) and a decrease in the HHI for the generics market segment (from 0.7+/
      0.2 to 0.6+/-0.3). There was a negative correlation between those variables that
      increased after the introduction of RPS (from -0.6 to -0.8). The HHI for brands
      and the dominant positions remained unchanged. CONCLUSION: After the
      implementation of RPS, the increased competition was mainly driven by economic
      and social agents in the generics market segment but not in the brands market
      segment.

PMID- 19839067
TI  - Developing competitive and sustainable Polish generic medicines market.
AB  - AIM: To descriptively analyze the policy environment surrounding the Polish
      generic medicines retail market. METHOD: The policy analysis was based on an
      international literature review. Also, a simulation exercise was carried out to
      compute potential savings from substituting generic for originator medicines in
      Poland using IMS Health pharmaceutical intelligence data. RESULTS: Poland has a
      mature, high-volume, low-value generic medicines market, primarily driven by the
      establishment of the reference price at the price of the cheapest medicine in
      combination with pricing regulation and the low level of medicine prices. The
      practice of discounting in the distribution chain implies that the National
      Health Fund and patients do not capture the potential savings from a generic
      medicines market where companies compete on price. This high-volume market has
      benefited in the past from the limited availability of originator medicines and a
      short data exclusivity period, even though there are no incentives for physicians
      to prescribe generic medicines and a financial disincentive for pharmacists to
      dispense generic medicines. Increased generic substitution would be expected to
      reduce public expenditure on originator medicines by 21%. CONCLUSION: To develop
      a competitive and sustainable market, Poland needs to consider moving away from
      competition by discount to competition by price. This could be achieved by
      replacing maximum distribution margins by fixed margins. Also, Poland may wish to
      raise reference prices as a temporary measure to boost market entry for medicine
      classes with few generic medicines.

PMID- 19839068
TI  - B-type natriuretic peptide as predictor of heart failure in patients with acute
      ST elevation myocardial infarction, single-vessel disease, and complete
      revascularization: follow-up study.
AB  - AIM: To assess the concentration of B-type natriuretic peptide (BNP) as a
      predictor of heart failure in patients with acute ST elevation myocardial
      infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI)
      with successful and complete revascularization. METHODS: Out of a total of 220
      patients with acute STEMI admitted to the Sisters of Mercy University Hospital in
      the period January 1 to December 31, 2007, only patients with acute STEMI
      undergoing primary PCI who had single vessel disease and were successfully
      revascularized were included in the study. Selected patients had no history of
      myocardial infarction or heart failure and a normal or near-normal left
      ventricular ejection fraction (> or =50%) assessed by left ventriculography at
      admission. Only 58 patients met the inclusion criteria for the study. Out of
      those, 6 patients refused to participate in the study, and another 5 could not be
      followed up, so a total of 47 patients were evaluated. Blood samples were taken
      for measurement of BNP levels at admission, 24 hours later, and 7 days later.
      Patients were followed up for 1 year. The primary outcome was reduction in left
      ventricular ejection fraction (LVEF) to <50% after 1 year. RESULTS: Patients who
      developed echocardiographic signs of reduced systolic function defined as
      LVEF<50% had significantly higher values of BNP (> or =80 pg/mL) at 24 hours
      (P=0.001) and 7 days (P=0.020) after STEMI and successful reperfusion. Patients
      who had BNP levels > or =80 pg/mL after 7 days were 21 times more likely to
      develop LVEF<50 (odds ratio, 20.8; 95% confidence interval, 2.2-195.2; P=0.008).
      CONCLUSION: BNP can be used as a predictor of reduced systolic function in
      patients with STEMI who underwent successful reperfusion and had normal ejection
      fraction at admission.

PMID- 19839069
TI  - Clinical value of serum HMGB1 levels in early detection of recurrent squamous
      cell carcinoma of uterine cervix: comparison with serum SCCA, CYFRA21-1, and CEA
      levels.
AB  - AIM: To evaluate the clinical value of serum high mobility group box chromosomal
      protein 1 (HMGB1) levels in making the early diagnosis of recurrent cervical
      squamous cell carcinomas (CSCC) and compare it with the value of serum squamous
      cell carcinoma antigen (SCCA), cytokeratin fragment (CYFRA) 21-1, and
      carcinoembryonic antigen (CEA) levels. METHODS: Immunohistochemical staining of
      tissue from 64 patients with recurrent CSCCs, 72 patients with non-recurrent
      carcinoma, and 28 healthy participants was performed to determine the expression
      of HMGB1 protein. The serum levels of the 4 markers in 112 patients with
      recurrent CSCC, 174 patients with non-recurrent disease, and 128 healthy
      participants were measured by enzyme-linked immunosorbent assay. The receiver
      operating characteristic (ROC) curves were constructed and the area under the
      curve (AUC) was calculated. RESULTS: Higher immunostaining score was found in
      recurrent CSCC tissue sections than in non-recurrent CSCC sections. Serum HMGB1
      levels in patients with recurrent CSCC were significantly higher than in patients
      with non-recurrent disease and healthy controls. The AUC of HMGB1, SCCA, CYFRA21
      1, and CEA was 0.816, 0.768, 0.703, and 0.625, respectively. HMGB1 had the best
      specificity and positive likelihood ratio (78.0% and 3.25, respectively), whereas
      SCCA had the best sensitivity and negative likelihood ratio (76.3% and 0.34,
      respectively). Parallel combined measurements increased the diagnostic
      sensitivity and serial combination increased the specificity. High serum HMGB1
      levels were inversely correlated with disease-free survival (P=0.009, Pearson
      chi(2) test) and overall survival (P=0.018). CONCLUSION: HMGB1 was overexpressed
      in recurrent CSCCs. Serum HMGB1 level could be a useful and specific marker for
      evaluating the disease recurrence and predicting prognosis in patients with CSCC.
      Serial combined measurements of serum HMGB1, SCCA, and CYFRA21-1 increased the
      diagnostic specificity, and parallel combined testing increased the diagnostic
      sensitivity.

PMID- 19839070
TI  - Consequences of untreated posttraumatic stress disorder following war in former
      Yugoslavia: morbidity, subjective quality of life, and care costs.
AB  - AIM: To assess long-term mental health outcomes in people who suffer from war
      related posttraumatic stress disorder (PTSD) but do not receive appropriate
      treatment. METHODS: We interviewed 264 subjects from former Yugoslavia, who lived
      in Croatia, Serbia, Germany, and the United Kingdom. All of them had suffered
      from PTSD at some point following the war, but never received psychiatric or
      psychological treatment. The interviews took place on average 10.7+/-3.0 years
      after the war-related trauma. Outcomes were current PTSD on the Clinician
      Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders
      IV, subjective quality of life (SQOL) on the Manchester Short Assessment of
      Quality of Life, and care costs. Socio-demographic characteristics, the level of
      traumatic war-events, and aspects of the post-war situation were tested for
      association with outcomes. RESULTS: Current PTSD was diagnosed in 83.7% of
      participants, the mean SQOL score was 4.0+/-0.9, and mean care costs in the last
      3 months exceeded euro1100 in each center. Older age, more traumatic war-events,
      lower education, and living in post-conflict countries were associated with
      higher rates of current PTSD. Older age, combat experience, more traumatic war
      events, being unemployed, living alone, being housed in collective accommodation,
      and current PTSD were independently associated with lower SQOL. Older age and
      living in Germany were linked to higher costs of formal care. CONCLUSION: People
      with untreated war-related PTSD have a high risk of still having PTSD a decade
      after the traumatic event. Their SQOL is relatively low, and they generate
      considerable care costs. Factors that have been reported as influencing the
      occurrence of PTSD also appear relevant for recovery from PTSD. Current PTSD may
      impair SQOL independently of social factors.

PMID- 19839071
TI  - Significance of off-hours in centralized primary percutaneous coronary
      intervention network.
AB  - AIM: To analyze the efficacy of a regionally organized primary percutaneous
      coronary intervention (PCI) network at the Heart Center, Semmelweis University
      Budapest, part of the "Budapest model," and the factors that influence it.
      METHODS: In order to investigate the differences between regular and off-hours
      patient care in a 24-hour myocardial infarction primary care system, we included
      1890 consecutive, unselected patients with ST-segment elevation myocardial
      infarction and followed them until at least one year. The follow-up was complete
      for all participants. RESULTS: The difference between regular hours and off-hours
      mortality was not significant either after 30 days (8.6% vs 8.8%, respectively)
      or after 1 year (15.3% vs 14.7%, respectively). The rate of patients with re
      infarction, frequency of re-intervention, and major adverse cardiac events,
      including death, re-infarction, re-intervention, and coronary artery bypass graft
      surgery, were similar in both patient groups. The time delay between the onset of
      chest pain and arrival to the clinic was 5.9+/-5.8 hours (mean+/- standard
      deviation) during regular hours and 5.2+/-4.6 hours during off-hours (P=0.235).
      Direct transport caused significant decrease in the 30-day and 1-year mortality
      independent of duty time (7.2% vs 9.9%, P=0.027; 12.6% vs 16.7%, P=0.028;
      respectively). CONCLUSION: Centralized primary PCI network of the "Budapest
      model" achieved the same level of patient care during both off-hours and regular
      hours.

PMID- 19839072
TI  - Validation of questionnaire estimating predictors of behavior intention to engage
      in first sexual intercourse among eighth-grade pupils.
AB  - AIM: To use structural equation modeling in testing the construct validity of the
      questionnaire on the first sexual intercourse among young adolescents. METHODS:
      Previously created questionnaire for the estimation of different factors
      influencing the intention to engage in the first sexual intercourse was
      validated. The data were gathered anonymously from a nationally representative
      sample of 1217 elementary school pupils aged 14-15 in Slovenia. The construct
      validity was determined by the structural equation modeling, LISREL 8.7. RESULTS:
      The reliability of the questionnaire was satisfactory (Cronbach alpha=0.73).
      Using the structural equation modeling analyses, the fit between empirical and
      theoretical models was confirmed, with 18 variables (17 independent and 1
      dependent) for 6 latent indicators (5 external and 1 internal). The measures of
      goodness of fit were chi2(80)=57.040; P=0.976; the root mean square error of
      approximation was <0.001; the root mean square residual was 0.0249; the goodness
      of fit index was 0.994; the adjusted goodness of fit index was 0.988; the normed
      fit index was 0.993; and the relative fit index was 0.986. The instrument
      explained 34% of the variance in behavior intention. CONCLUSION: The construct
      validity of the questionnaire on the intention to engage in the first sexual
      intercourse among young adolescents was satisfactory. This questionnaire could be
      a useful tool in health promotion programs.

PMID- 19839074
TI  - PharmaNostra under fire.

PMID- 19839073
TI  - Transition from longitudinal to block structure of preclinical courses: outcomes
      and experiences.
AB  - AIM: To evaluate the transition from a longitudinal to block/modular structure of
      preclinical courses in a medical school adapting to the process of higher
      education harmonization in Europe. METHODS: Average grades and the exam pass
      rates were compared for 11 preclinical courses before and after the transition
      from the longitudinal (academic years 1999/2000 to 2001/2002) to block/modular
      curriculum (academic years 2002/2003 to 2004/2005) at Zagreb University School of
      Medicine, Croatia. Attitudes of teachers toward the 2 curriculum structures were
      assessed by a semantic differential scale, and the experiences during the
      transition were explored in focus groups of students and teachers. RESULTS: With
      the introduction of the block/modular curriculum, average grades mostly
      increased, except in 3 major courses: Anatomy, Physiology, and Pathology. The
      proportion of students who passed the exams at first attempt decreased in most
      courses, but the proportion of students who successfully passed the exam by the
      end of the summer exam period increased. Teachers generally had more positive
      attitudes toward the longitudinal (median [C]+/-intequartile range [Q], 24+/-16)
      than block/modular curriculum (C+/-Q, 38+/-26) (P=0.001, Wilcoxon signed rank
      test). The qualitative inquiry indicated that the dissatisfaction of students and
      teachers with the block/modular preclinical curriculum was caused by perceived
      hasty introduction of the reform under pressure and without much adaptation of
      the teaching program and materials, which reflected negatively on the learning
      processes and outcomes. CONCLUSION: Any significant alteration in the temporal
      structure of preclinical courses should be paralleled by a change in the content
      and teaching methodology, and carefully planned and executed in order to achieve
      better academic outcomes.

PMID- 19839076
TI  - Science world.

PMID- 19839075
TI  - There is more to being a doctor than having a large wallet.

PMID- 19839077
TI  - Pink ribbon day.

PMID- 19839078
TI  - Kidney stones.  Preventing formation.

PMID- 19839079
TI  - Many lose sleep due to economic issues.

PMID- 19839080
TI  - Vitamin D.  Bone benefits and beyond.

PMID- 19839081
TI  - I have an anal fissure that isn't getting better even though I've increased my
      fiber and water intake over past few months.  My doctor is recommending surgery
      to cut part of the anal sphincter.  Are there any other treatment options?

PMID- 19839082
TI  - Is there a role for lifestyle education in the management  of gastro-oesophageal
      reflux disease?

PMID- 19839083
TI  - Radiofrequency perforation of the pulmonary valve in an adult     with tetralogy
      of Fallot and pulmonary atresia.

PMID- 19839084
TI  - Anxiety and depression among long-term survivors of cancer in Australia: results
      of a population-based survey. Comment.

PMID- 19839085
TI  - New horizons for mental health in the UK.

PMID- 19839086
TI  - Established stem cell lab at the University of Prince Edward Island.

PMID- 19839087
TI  - Additional perspectives on causes of educational debt.

PMID- 19839088
TI  - Questions claims in unwanted horse survey report.

PMID- 19839090
TI  - Influential professionals inspiring younger generations.

PMID- 19839089
TI  - Looking to the future of veterinary medicine.

PMID- 19839091
TI  - Diagnosis SOS.

PMID- 19839095
TI  - Lipids.

PMID- 19839096
TI  - [Traumatic dislocation of distal radio ulnar joint].

PMID- 19839097
TI  - [Who am I? Joseph Toynbee].

PMID- 19839098
TI  - Laparoscopic entry roundtable.

PMID- 19839099
TI  - Drosophila stathmin is required to maintain tubulin pools.

PMID- 19839100
TI  - WHO's Western Pacific region agrees tobacco-control plan.

PMID- 19839102
TI  - Rising star.

PMID- 19839101
TI  - Placebo controls, exorcisms, and the devil.

PMID- 19839103
TI  - Bridge of signs: can sign language empower non-deaf children to triumph over
      their communication disabilities?

PMID- 19839104
TI  - Educational programs for deaf students. Schools and programs in the United
      States.

PMID- 19839105
TI  - Educational programs for deaf students. Schools and programs in Canada.

PMID- 19839106
TI  - Educational programs for deaf students. Postsecondary programs.

PMID- 19839107
TI  - University and college programs for personnel in deafness.

PMID- 19839108
TI  - Programs for deaf-blind children and adults.

PMID- 19839109
TI  - Advocacy, support, and rehabilitation programs.

PMID- 19839110
TI  - Research on deafness. Doctoral dissertations.

PMID- 19839111
TI  - Research on deafness. Gallaudet University dissertations and theses.

PMID- 19839113
TI  - An unremembered diversity: mixed husbandry and the American grasslands.
AB  - The Green Revolution of the 1960s brought about a dramatic rise in global crop
      yields. But, as most observers acknowledge, this has come at a considerable cost
      to biodiversity. Plant breeding, synthetic fertilizers, and mechanization
      steadily narrowed the number of crop varieties commercially available to farmers
      and promoted fencerow-to-fencerow monocultures. Many historians trace the origins
      of this style of industrialized agriculture to the last great plow-up of the
      Great Plains in the 1920s. In the literature, farms in the plains are often
      described metaphorically as wheat factories, degrading successive landscapes.
      While in many ways these farms were a departure from earlier forms of husbandry
      in the American experience, monocultures were quite rare during the early
      transformation of the plains. Analysis of a large representative sample, based on
      manuscript agricultural censuses and involving twenty-five townships across the
      state of Kansas, demonstrates that diverse production reached even the most
      challenging of plains landscapes.

PMID- 19839114
TI  - Supporting culture change: working toward smarter state nursing home regulation.
AB  - The traditional nursing home regulatory approach, which uses survey and
      enforcement to achieve performance improvement, has created tensions between
      providers and surveyors. It has had limited success in improving quality overall
      and not necessarily allowed innovation to flourish. This has been the perception
      of many homes wanting to undergo transformative "culture change" reforms. To move
      toward a new model of nursing home regulation, the states and federal government
      must strike a balance between the traditional regulatory approach to weed out
      substandard facilities and a partnership model aimed at promoting high
      performance. This issue brief highlights the importance of how such a model is
      structured, as well as the need to adequately train and educate regulatory staff
      and providers about culture change. Regulators, providers, consumer groups,
      residents, and their families also will need to commit to the principles of
      person-centered care to ensure the success of the new collaborative approach.

PMID- 19839115
TI  - Peasant friendly plant breeding and the early years of the green revolution in
      Mexico.
AB  - Despite their success in boosting cereals production overall, the Green
      Revolution programs of the 1950s and 1960s were often criticized for failing to
      achieve their declared aim of alleviating world hunger. Most critics argued that
      the programs had produced a technology unsuited to the needs of small peasant
      farmers. This paper explores why such inappropriate technology might have been
      developed, focusing on the early years of the Rockefeller Foundation's Mexican
      Agricultural Program (MAP). It shows that some foundation officers as well as
      agricultural advisors had prior experience of the problems faced by small farmers
      in the United States and elsewhere. Moreover, the foundation's expressed concern
      for rural poverty does not appear to have been mere posturing by an organization
      anxious to be seen as an agent of philanthropy. Furthermore, the program's early
      work in maize-breeding was well tailored to the conditions of Mexican
      agriculture. Once the MAP was up and running, however, it became apparent that
      the task of getting new varieties and cultivation practices to small farmers was
      going to be difficult. Needing to make some kind of impact quickly, MAP staff
      chose to concentrate upon projects that were likely to find a rapid uptake. This
      meant setting aside the needs of peasant farmers to develop high-yielding
      varieties suited to large commercial farms.

PMID- 19839116
TI  - A global vision for care of older adults: groundbreaking statement is signed by
      32 specialty nursing organizations.

PMID- 19839117
TI  - Expanding the gerontological nursing role in Guided Care.

PMID- 19839118
TI  - Reducing avoidable hospitalizations in nursing could save $1 billion annually--so
      why delay?

PMID- 19839119
TI  - [Public and private museums in Cameroon].

PMID- 19839120
TI  - [The "troublesome" ethnographer, or the vicissitudes of creation of the national
      museum of Cameroon].

PMID- 19839121
TI  - [Which past for the Khoisan? Representations, memory, cultural inheritance].

PMID- 19839122
TI  - Sterotypic vision: the "moral character" of the Senufo in colonial and
      postcolonial discourse.

PMID- 19839123
TI  - [The Massa people and Moussa's water: regional cults, local traditions, and
      witchcraft in West Africa].

PMID- 19839124
TI  - [A long-term view of Soninke migrations: strategies and identities].

PMID- 19839125
TI  - [Housing in Montpellier in 1756: a study of urban residential patterns in the
      18th century].

PMID- 19839126
TI  - [An approach to housing in Lyons in the 17th-18th centuries: leasing].

PMID- 19839127
TI  - [Standardization of reviews of scientific publications].

PMID- 19839128
TI  - [The residential mobility of Francois Valesque (1706-1791), a notable of Lyons].

PMID- 19839129
TI  - [Urban residence in Paris in the 18th and early 19th centuries].

PMID- 19839130
TI  - [A study of the link between social and constructed space: reflections on the
      renewal of the Lyons city center in the 19th century].

PMID- 19839131
TI  - [The seemingly lethal simvastatin...].

PMID- 19839132
TI  - Quality assessment of the procedure for determination of heavy metals on reactive
      carriers.
AB  - Quality control and validity check of the solid-phase spectrophotometric
      procedure (Me-SPS) for determination of heavy metals important in pharmaceutical
      practice: zinc (Zn-SPS), lead (Pb-SPS), and cobalt (Co-SPS) were performed using
      a very simple and informative prevalidation concept. Further, metrological
      characteristics of the Me-SPS procedure together with the diagnosis of particular
      prevalidation steps were evaluated. Favourable prevalidation characteristics,
      i.e., ideal analytical function, homogeneity of data material, low limit of
      quantitation, and acceptable accuracy verified the quality of the Me-SPS
      procedure and pointed to the limitations of some investigated systems.

PMID- 19839133
TI  - First total synthesis and biological screening of hymenamide E.
AB  - A new potent bioactive, proline-rich cyclic heptapeptide hymenamide E (13) was
      synthesized using the solution phase technique by cyclization of the linear
      peptide Boc-Phe-Pro-Thr-Thr-Pro-Tyr-Phe-OMe (12) after proper deprotection at
      carboxyl and amino terminals. Linear peptide segment was prepared by coupling the
      tripeptide unit Boc-Phe-Pro-Thr-OH (10a) with the tetrapeptide unit Thr-Pro-Tyr
      Phe-OMe (11a) using dicyclohexylcarbodiimide as the coupling agent and N
      methylmorpholine as the base. Structures of all new compounds were characterized
      by IR, 1H NMR spectral data as well as elemental analyses. In addition, the
      structure of compound 13 was verified by 13C NMR, fast atom bombardment mass
      spectroscopy and differential scanning calorimetry. The newly synthesized
      cyclopeptide was screened for its antibacterial, antifungal and anthelmintic
      activities against eight pathogenic microbes and two earthworm species. Compound
      13 showed potent antifungal activity against Candida albicans and Ganoderma
      species comparable to that of griseofulvin as a reference drug and potent
      anthelmintic activity against earthworms Megascoplex konkanensis and Eudrilus
      species in comparison to piperazine citrate.

PMID- 19839134
TI  - Preparation and in vitro characterization of slow release testosterone
      nanocapsules in alginates.
AB  - Slow release testosterone-loaded nanocapsules in alginate, biodegradable
      hydropolymer, were prepared by in situ nanoemulsion-polymer crosslinking
      approach. Different formulations varying in the drug loading solvent phase were
      prepared. Four different drug-loading solvents were assayed and the food grade
      hexane provided nanocapsules testosterone load of 30%. Testosterone loading was
      confirmed by FT-IR, DSC and quantitated by HPLC. Prepared nanocapsules appeared
      spherical with a dense drug core in transmission electron microscopy studies.
      Hydrodynamic diameter of nanocapsules was 34.5 +/- 1.7 nm, with a Gaussian
      distribution and the zeta potential -5.0 meV. Sustained diffusive drug release
      was observed in vitro, following zero order kinetics releasing the drug payload
      over a period of 48 hours. Embedding testosterone in alginate provided sustained
      release. Different drug loading solvents have distinct influence on drug loading
      and nanocapsules size distribution. The nanocapsulation technique developed can
      be a good choice for the development of different sustained steroid hormonal drug
      carriers.

PMID- 19839135
TI  - Spectrofluorimetric determination of ciclopirox olamine via ternary complex with
      Tb(III) and EDTA.
AB  - A highly sensitive and selective spectrofluorimetric method was developed for the
      determination of ciclopirox olamine in raw material and in dosage forms. The
      proposed method is based on the formation of a ternary complex with Tb(III) in
      the presence of ethylenediaminetetraacetic acid. It was found that this complex
      manifests intense fluorescence at lambda(em) 489 and 545 nm with excitation at
      295 nm. Different experimental parameters affecting the fluorescence intensity of
      the complex were carefully studied and incorporated into the procedure. Under the
      described conditions, the method is applicable over the concentration range 30
      150 and 10-70 ng mL(-1) with minimum detectability of 6.7 and 0.9 ng mL(-1) at
      lambda(em) 489 and 545 nm, respectively. The mean percentage recovery at
      lambda(em) 489 and lambda(em) 545 nm ranged between 98.7 and 100.2 for the pure
      substance, solution, and cream. Relative error of 0.1-0.4% and RDS of up to 0.9%
      were estimated at lambda(em) 489 and 545 nm. A proposal of the reaction pathway
      is given.

PMID- 19839136
TI  - Synthesis and antimicrobial evaluation of some new thienopyrimidine derivatives.
AB  - Reaction of heteroaromatic o-aminonitrile with ethyl N
      [bis(methylthio)methylene]amino acetate resulted in annelation of a thieno[3,2
      e]imidazo[1,2-c]pyrimidine moiety in a one step process. [1,2,4]Triazolo[4,3
      c]thieno- [3,2-e]pyrimidine derivatives were prepared by initial treatment of o
      aminonitrile with carbon disulfide, followed by methylation with methyl iodide
      and subsequent reaction with benzhydrazide and thiosemicarbazide, respectively.
      Hydrazinothieno[2,3-d]pyrimidine was prepared by cyclization of heteroaromatic o
      aminoester with formamide, followed by chlorination and subsequent displacement
      with hydrazine. Treatment of the hydrazino derivative with acetylacetone,
      benzaldehyde and acetic anhydride afforded pyrazolylpyrimidine,
      benzylidenehydrazonopyrimidine and triazolopyrimidine derivatives, respectively.
      Some of these derivatives exhibited pronounced antimicrobial activity.

PMID- 19839137
TI  - Evaluation of a drug with wax-like properties as a melt binder.
AB  - The study investigates ibuprofen with wax-like properties as a multifunctional
      agent (as an active component and as a melt binder). Binding efficiency was
      compared with granules prepared by wet granulation using polyvinylpyrollidone
      (PVP K-30) as a binder for micromeritic, physical and mechanical properties such
      as angle of repose, particle size distribution Carr's index, Hausner's ratio,
      crushing strength, percentage fines, Heckel plot study and tensile strength. To
      check the binder distribution during melt granulation, the content uniformity was
      determined. To check changes in the physical state of ibuprofen, XRPD, DSC and
      FTIR studies were carried out. The present study underlines the fact that
      ibuprofen may be adopted as a binder in ibuprofen formulations using the melt
      granulation technique.

PMID- 19839138
TI  - Dissolution of celecoxib from mucoadhesive disks based on polyaspartamide
      derivatives.
AB  - A series of mucoadhesive disks with celecoxib as a model drug of very low aqueous
      solubility were prepared and characterized. Two polymers of polyaspartamide type,
      poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA, 1) and its thiolated
      analogue poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)]-poly[alpha,beta-(N-2
      thioethyl-DL-aspartamide)] copolymer (PHTA, 2a,b), and two commercially available
      polymers Carbopol 934P and hydroxypropylmethyl cellulose 4000 were used as
      excipients. Disks containing a mixture of equivalent amounts of thiomer 2b and
      Carbopol 934P as an excipient exhibited the highest dissolution rate.

PMID- 19839139
TI  - Composition and antimicrobial activity of essential oil from the fruits of Amomum
      cannicarpum.
AB  - Essential oil from the fruits of Amomum cannicarpum (Wight) Bentham ex Baker
      (Zingiberaceae) was hydrodistilled and characterized by gas chromatography-mass
      spectrometry (GC-MS). Major constituents of the oil were beta-pinene (14.00%),
      elemol (10.45%) and alpha-cadinol (8.50%). Thirty-three (91.48%) out of forty-one
      constituents were identified by GC-MS and subsequent data analysis. Antimicrobial
      activity of the oil against Gram-positive and Gram-negative bacteria and some
      fungi, was determined by the disc diffusion assay. The oil showed good
      antibacterial activity against Salmonella typhi, Pseudomonas aeruginosa and
      Proteus vulgaris and very good antifungal activity against Candida albicans and
      C. glabrata.

PMID- 19839140
TI  - Optimized determination of lorazepam in human serum by extraction and high
      performance liquid chromatographic analysis.
AB  - The present research was designated to evaluate a rapid and sensitive method for
      determining low concentrations of the highly active drug lorazepam in serum.
      Isolation of the drug from biological fluid after addition of nordazepam as the
      internal standard was achieved using a simple liquid-liquid extraction with
      dichloromethane and the extracted compounds were quantified by high-performance
      liquid chromatography. Chromatographic separation on a reversed phase column
      containing a stationary phase with low silanol activity resulted in a perfectly
      symmetrical peak with a tailing factor of 1.0. The limit of quantitation in serum
      is 2.5 ng mL(-1) for both lorazepam and internal standard. The procedure is rapid
      and sensitive enough for determination of lorazepam in serum.

PMID- 19839141
TI  - Antioxidant activity of Desmodium gangeticum and its phenolics in arthritic rats.
AB  - Total alcoholic extract of Desmodium gangeticum, which exhibited significant anti
      inflammatory activity, was evaluated for the possible mode of action by studying
      its antioxidant potential in adjuvant-induced arthritic rats. Activity guided
      fractionation and isolation were carried out. The phenolics fraction showed
      maximum potency. Solid phase extraction followed by preparative HPLC of the
      active phenolic fraction yielded for the first time two potent antioxidant
      compounds, caffeic acid and chlorogenic acid, from this plant. The biological
      antioxidant defense system, involving superoxide dismutase, glutathione and
      catalase, showed a significant increase with their levels close to the normal
      control with a decrease in the lipid peroxide content upon administration of D.
      gangeticum extract (100 mg kg(-1)) and its phenolics (50 mg kg(-1)) in arthritic
      rats, thereby indicating the extracts antioxidant property under arthritic
      conditions.

PMID- 19839142
TI  - Good clinical practice: issues and challenges.

PMID- 19839143
TI  - Patient attendance at a major accident and emergency department: are public
      emergency services being abused?
AB  - A total of 37,152 patients attended the Accident & Emergency (A&E) Department of
      Hospital Universiti Kebangsaan Malaysia (HUKM) from 1st January to 31st December
      1998. Attendance during early hours (midnight to 0659 hrs.) constituted only
      10.4% (3853 cases) whereas that for three other time periods of 0700-1159 hrs.,
      1200-1759 hrs., and 1800-2359 hrs. was 29.4% (10,927 cases), 30.8% (11,448
      cases), and 29.4% (10,924 cases) respectively. Two hundred and fifty-one patients
      were direct admissions from other hospitals into our hospital wards and they
      attended the A&E department for registration purposes only. Of the remaining
      36,901 that were triaged, 196 (0.5%) were resuscitation cases [Triage 1], 3648
      (9.9%) were emergency cases [Triage 21, 18,935 (51.3%) were urgent cases [Triage
      3], and 14,122 (38.3%) were non-urgent cases [Triage 4]. Despite fluctuations in
      monthly patient attendance, the proportions of patients according to time of
      attendance, age group, gender and triage categories remained similar throughout.
      As majority of patients attended during convenient hours (89.6% from 0700-2359
      hrs.) and a high proportion of patients (38.3%) belonged to the non-urgent Triage
      category, we feel that public emergency services are possibly being abused.

PMID- 19839144
TI  - Preliminary report on somatostatin receptor imaging in rare endocrine tumours.
AB  - Our preliminary experience of Somatostatin Receptor Positive Tumour Scintigraphy
      (SRPTS) in the management of some rare neuroendocrine tumours is highlighted. Six
      patients were evaluated using SRPTS. A single patient each with Zollinger-Ellison
      syndrome, recurrent medullary carcinoma of thyroid and Stage IV neuroblastoma.
      Two patients with phaeochromocytoma, and one patient with suspected insulinoma
      were evaluated. SRPTS was useful in three of the six patients studied i.e.
      patient with gastrinoma, recurrent medullary carcinoma of thyroid and metastatic
      neuroblastoma. SRPTS although expensive is a useful and cost-effective approach
      of rare endocrine tumours and it role as a first line tool in the diagnosis is
      discussed.

PMID- 19839145
TI  - Demographic characteristics and prevalence of other sexually transmitted diseases
      in HIV-positive patients seen in the Dermatology cum Genitourinary Clinic,
      Hospital Sultanah Aminah, Johor Bahru.
AB  - The demographic characteristics, risk behaviourand prevalence of other sexually
      transmitted diseases (STDs) were determined in 132 HIV-infected individuals seen
      in a Dermatology cum Genitourinary Clinic, Hospital Sultanah Aminah Johor Bahru.
      Sixty-one (46.2%) were Malays, 37.9% Chinese, 10.6% Indians and 5.3% were of
      other ethnic groups. The male to female ratio was 4.5:1. Most of the patients
      (82.5%) were between 20 to 40 years-old. Seventy (53.0%) were single, 34.1% were
      married and 7.5% were divorcees. The majority of them (97.7%) were heterosexual.
      Fifty seven (53.3%) of our male patients patronised commercial workers. Eighty
      one (61.8%) were not intravenous drug users (IVDU). Of the 50 IVDUs, 24 had
      multiple sexual exposures. Fifty-three (48.2%) of the 109 patients screened for
      STDs had one or more other STDs. Thirty-four patients (31.9%) reported one STD in
      the past and 3.6% reported two STDs in the past. Fifty-six patients (42.4%) had
      developed AIDS. Thirteen had passed away. The main mode of transmission of HIV
      infection in this population is through heterosexual intercourse and the
      prevalence of STDs is high. These findings indicate a need to advocate
      responsible sexual behaviour and to detect as well as treat STDs early to prevent
      the sexual transmission of HIV.

PMID- 19839146
TI  - Prevalence, clinical predictors and diagnosis of gastro-oesophageal reflux in
      children with persistent respiratory symptoms.
AB  - OBJECTIVES: This was a cross sectional study conducted in the Paediatric
      Institute among infants and children with chronic respiratory symptoms with the
      following objectives: i) to determine the prevalence of gastro-oesophageal reflux
      in children with persistent respiratory symptoms, ii) to identify the clinical
      predictors of GOR (Gastro-oesophageal reflux) in children with persistent
      respiratory symptoms and iii) assess the validity of abdominal ultrasound, barium
      oesophagogram and chest radiograph in diagnosing GOR in these patients. MATERIALS
      AND METHODS: Forty-four patients were recruited over a period of six months. All
      the presenting symptoms were identified. The patients were subjected to chest
      radiograph, abdominal ultrasound, barium oesophagogram and 24-hour pH oesophageal
      monitoring. The predictive validity of clinical symptoms, chest radiograph,
      abdominal ultrasound and barium oesophagogram were assessed. Twenty-four hours
      oesophageal pH was the gold standard to diagnose GOR. RESULTS: The mean age of
      patients was 9.1 months (1-58 months). Thirty-one patients (70.5%) were confirmed
      to have GOR by pH study. Respiratory symptoms alone were not useful to predict
      GOR. Cough had the highest sensitivity of 51.6%. Stridor, wheeze and choking each
      had a specificity of 76%. Wheeze, vomiting, choking and stridor were identified
      to have high specificity (90-100%) in diagnosing GOR when any two symptoms were
      taken in combination. Collapse/consolidation was the commonest radiological
      abnormality but had low sensitivity (35.5%) and specificity (53.8%). However
      hyperinflation on chest radiograph had a specificity of 92.3% with positive
      predictive value of 80% in diagnosing GOR. Barium oesophagogram has low
      sensitivity (37.9%) and moderate specificity (75%) in diagnosing GOR in children
      with respiratory symptoms. Abdominal ultrasound was a valid mode of diagnosing
      GOR when there were three or more reflux episodes demonstrated during the
      screening period with a specificity of 90.9%. However the sensitivity was low
      i.e. 20-25%. The specificity increased to 90-100% when two positive tests were
      taken in combination (abdominal ultrasound and barium oesophagogram). However the
      sensitivity remained low (10-20%). Chest radiograph did not improve the
      predictive value when considered with the above tests. Combination of clinical
      symptoms were useful as clinical predictors of GOR. In the absence of a pH
      oesophageal monitoring, a combination of barium oesophagogram and ultrasound may
      be helpful in diagnosing GOR.

PMID- 19839147
TI  - Dialysis provision in Malaysia.
AB  - We determined the provision for dialysis treatment in Malaysia. There were 181
      dialysis centres as at 1st June 1999 (161 Haemodialysis (HD) and 20 Continuous
      Ambulatory Peritoneal Dialysis (CAPD) centres), providing treatment for 5614
      patients. This is equivalent to an estimated prevalence rate of 253 patients per
      million population (pmp) and new dialysis acceptance rate of 49 patients pmp.
      Dialysis facilities were widely distributed throughout the country though rather
      unevenly among states. Penang, Selangor/KL, Malacca led with number of dialysis
      patients pmp ranging from 417 to 480. Kelantan and Sabah had the lowest provision
      with 51 and 64 patients pmp respectively. There were more centres and HD capacity
      in the private sector while the Non-Government Organisation and public sectors
      had about the same capacity. However the public sector had more patients on
      account of availability of CAPD and home HD services, as well as low HD capacity
      to patient ratio. The number ofcentres, HD capacity and patients have increased
      rapidly especially since 1991; the estimated growth rates were 16.5 centres/year,
      658 capacity/year, and 392 patients/year respectively. There was also a trend
      toward increasing over-capacity in the private and NGO sectors. In conclusion,
      the level of dialysis provision is increasing, indicating increasing
      accessibility of dialysis treatment in Malaysia. Over-capacity is a concern in
      the private and NGO sectors. Thus funding agencies should be encouraged to source
      provision from those sectors. The public sector still has the crucial role of
      providing for under-served areas in the country.

PMID- 19839148
TI  - Clustering of hypertension, abnormal glucose tolerance, hypercholesterolaemia and
      obesity in Malaysian adult population.
AB  - We determine the prevalence and determinants of clustering of hypertension,
      abnormal glucose tolerance, hypercholesterolaemia and overweight in Malaysia. A
      national probability sample of 17,392 individuals aged 30 years or older had
      usable data. 61% of adults had at least one risk factor, 27% had 2 or more risk
      factors. The observed frequency of 4 factors cluster was 6 times greater than
      that expected by chance. Indian and Malay women were at particular high risk of
      risk factors clustering. Individuals with a risk factor had 1.5 to 3 times higher
      prevalence of other risk factors. Ordinal regression analyses show that higher
      income, urban residence and physical inactivity were independently associated
      with risk factors clustering, lending support to the hypotheses that risk factors
      clustering is related to lifestyle changes brought about by modernisation and
      urbanisation. In conclusion, risk factor clustering is highly prevalent among
      Malaysian adults. Treatment and prevention programme must emphasise the multiple
      risk factor approach.

PMID- 19839149
TI  - Maternal deaths due to liver disease in Malaysia.
AB  - Liver disease is an important and serious condition in pregnancy. The
      Confidential Enquiries Into Maternal Deaths in Malaysia showed that there were 23
      maternal deaths attributed to liver disease between 1991-1994. Over the same
      period, there were 1066 reported maternal deaths with 929 of them being due to
      direct and indirect causes. Thus 2.15% of such deaths were due to liver disease
      in Malaysia. The three main causes of maternal deaths due to liver disease in
      pregnancy were hepatitis (6 cases), acute fatty liver in pregnancy (6 cases) and
      septicaemia (4 cases). Liver disease is common at a mean of thirty weeks of
      gestation with a preponderance to women of low parity. Only two patients in this
      series had no antenatal care. The majority of cases (45.8%) presented between 28
      37 weeks of gestation. All cases delivered by spontaneous vaginal delivery.
      Remediable factors that were identified included failure to appreciate the
      severity of disease. Case summaries of all the cases of maternal deaths due to
      liver disease are discussed and a guideline to management of liver disease in
      pregnancy presented.

PMID- 19839150
TI  - Urine protein excretion among Chinese patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Urinary excreton of low molecular weight proteins such as beta2
      microglobulin and retinol binding protein (RBP), and enzymes such as N-acetyl
      beta-D-glucosaminidase (NAG), may be useful as indicators of renal tubular
      dysfunction in diabetes mellitus. OBJECTIVE: To describe the profile of urinary
      protein and enzyme excretion in 240 Chinese patients with type 2 diabetes
      mellitus in Singapore. MATERIALS AND METHODOLOGY: Cross-sectional study of
      consecutive patients presenting for follow-up at a Government primary care
      clinic. Information was obtained from interview, physical examination and
      laboratory analysis. Data analysis included descriptive statistics on urinary
      protein and enzyme excretion, comparison of unadjusted and adjusted means of
      these among patient subgroups, as well as correlation with control of diabetes
      and other clinical parameters. RESULTS: Albuminuria correlated with urine beta2
      microglobulin (r=0.34, p<0.01) and RBP (r=0.46, p<0.01). Hypertensive patients
      had significantly higher mean urine albumin (geometric mean 15.13 mg/gCr) and
      beta2-microglobulin (363.18 microg/gCr) levels compared to patients without
      hypertension (7.07 mg/gCr; 219.20 microg/gCr; p<0.05). Patients with
      complications of diabetes also had higher albumin (15.55 vs 6.20 mg/gCr), beta2
      microglobulin (344.47 vs 288.83 microg/gCr) and RBP excretion (152.02 vs 94.54
      mg/gCr). Two-hour postprandial sugar correlated with beta2-microglobulin (r=0.33,
      p<0.01), RBP (r=0.35, p<0.01) and NAG (r=0.28, p<0.01). Urinary protein excretion
      did not correlate with HbA1c, fasting blood sugar, age of patient or duration
      since diagnosis. CONCLUSION: These results among 240 Chinese patients in
      Singapore were consistent with reports from other study populations.

PMID- 19839151
TI  - Nasopharyngeal carcinoma: a delay in diagnosis.
AB  - One hundred consecutive newly diagnosed patients with nasopharyngeal carcinoma
      (NPC) since January 1994 were the subjects for studying various factors that
      contribute to the delay in the confirmation of the diagnosis. Seventy-nine of
      them were males and the peak age of incidence was the fifth decade. Ninety two
      percent were Chinese, 7% Malay and 1% Indian. Seventy six percent were
      agriculture workers or labourers with 66% having either no formal education (16%)
      or only primary level education (50%). In 50% of patients neck swelling was the
      first presenting symptom, 26% had nasal symptoms, 12% ear symptoms and 11% has
      symptoms due to intracranial extension of tumour. As many as 80% were at UICC
      Stage IV at the time of diagnosis. While the median delay, on the part of
      patients, in consulting a doctor was 2.5 days, the median delay on the part of
      the doctors to confirm the diagnosis of NPC was 127 days, the delays was
      particularly worse when the patients presented with ear symptoms (266 days)
      followed by those with neck swelling (94 days). For those patients who were
      required to undergo more than one nasopharyngoscopy and biopsy the median
      doctor's delay was 144 days. Since 82% of patient's had first consulted general
      practitioners, it is suggested that their level of awareness with regards to the
      diagnosis of NPC be significantly raised so that the delay on their part be
      greatly minimized.

PMID- 19839152
TI  - Factors related to adverse outcome in inpatients with diabetic foot.
AB  - Sixty inpatients with diabetic foot were studied prospectively at the Orthopaedic
      wards of Hospital Kuala Lumpur. Data was evaluated to document the patient
      profile and the factors that were associated with a major amputation (either
      above knee or below knee) of the lower limb. Factors that were associated with
      increased risk of amputation were a low education level, manual occupation, poor
      foot care, peripheral vascular insufficiency of the lower limb, insulin
      dependence, anaemia and leucocytosis. However only anaemia, leucocytosis and
      hyperglycaemia were statistically significant in predicting a more adverse
      surgical procedure. This study recommends that foot care awareness and practice
      is important. This can be effectively dealt with at specially organised, multi
      disciplinary Diabetic Foot Clinics.

PMID- 19839153
TI  - Pancreatic insulinomas--a study of 15 cases from 1978-98.
AB  - Fifteen cases of insulinoma were managed at HUKM over a period of 20 years.
      Although all patients presented with neurological symptoms, the diagnosis was
      delayed in all. Fasting hypoglycaemia and the measurement of C-peptide levels
      eventually made the diagnosis. Pre-operative localization investigations were not
      particularly useful. Intraoperative ultrasound (IOUS) detected 72% of the
      insulinomas, while 93% of the insulinomas were identified intraoperatively by
      palpation. All the insulinomas were detected intraoperatively with the
      combination of the two techniques. Twelve of 15 patients had benign adenomas
      including one patient with MEN-1 syndrome. Two patients had malignant
      insulinomas. One patient refused surgery. Nine patients underwent pancreatic
      resections and the remaining 5 patients had the adenomas enucleated.

PMID- 19839154
TI  - Poor bowel preparation in patients undergoing colonoscopy.
AB  - A prospective analysis of 500 consecutive patients undergoing colonoscopy at the
      endoscopy unit of Hospital UKM under the care of the surgical unit was analysed.
      All colonoscopies were supervised by one of two consultant surgeons. The bowel
      preparation was graded from grade 1 to 4 according to established criteria. All
      patients had 3 litres of colonic lavage solution as bowel preparation. One
      hundred and two patients (20.4%) were considered to have poor bowel preparation,
      while 398 patients (79.6%) had good bowel preparation. Statistically significant
      factors that resulted in poor bowel preparation included age <20 years and >60
      years (p<0.0001), and inpatients (p<0.0193). There was no significant difference
      in respect to sex, ethnic groups and the indication for colonoscopy. We conclude
      that young adults and the elderly as well as inpatients are more likely to have a
      poor bowel preparation using the standard regime.

PMID- 19839155
TI  - Familial hyperlipidaemia in Malaysian children.
AB  - This paper highlights two cases of paediatric familial hyperlipidaemia
      (hypercholesterolaemia and hypertriglyceridaemia). The first case was an 11 year
      old Chinese boy, a "homozygous" (Type II) hypercholesterolaemic patient. He had
      extremely high blood cholesterol level (19.4 mmol/l), severe multiple xanthoma
      and abnormal resting electrocardiogram. He had repeated heart attacks and died at
      the age of 15 in spite of early intervention, treatment and follow up. The second
      case was a 2 1/2 years old girl who had severe hypertriglyceridaemia. She had
      raised cholesterol (6.2 mmol/l) and extremely high triglycerides (14.8 mmol/l).
      The patient did not resemble Type I lipoproteinaemia which is classically seen in
      childhood. On the contrary, the patient exhibited clinical and biochemical
      manifestations of a Type V lipoproteinaemia which often occurs in adults. Apart
      from a Type V lipoprotein pattern, the patient had low post hepatic lipase
      activity (PHLA), Apo C II and Apo E2/E3 phenotype. In addition, the lipid profile
      of her family members (both the parents and brothers) had raised triglycerides
      and thus ruled out the Type I lipoprotein inheritance pattern, which is an
      autosomal recessive condition. The issue of paediatric hyperlipidaemia, their
      management and treatments are discussed.

PMID- 19839156
TI  - Disseminated histoplasmosis in AIDS: a report of three patients.
AB  - Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Although
      uncommon, it should be considered among the list of important opportunistic
      infections in severely immunocompromised patients. Patients living with AIDS are
      at particular risk of disseminated histoplasmosis. Diagnosis requires a high
      level of clinical suspicion. The infection is best confirmed by demonstration of
      the organism in tissue specimens or by culture. Amphotericin B is the most
      effective drug for severe disseminated histoplasmosis. Response is good but life
      long maintenance is required to prevent relapse.

PMID- 19839157
TI  - An unusual presentation of renal parenchymal malacoplakia.

PMID- 19839158
TI  - Pulmonary siderosis in an arc welder.
AB  - An asymptomatic subject with radiographic changes due to welders' siderosis is
      described. This condition has not been well recognized and described in our
      community. Siderosis of the lung is generally considered to be a benign condition
      not associated with respiratory symptoms. However, recent reports have associated
      welding with various disorders of pulmonary function as well as lung cancer.
      There is a need for future epidemiological studies to better define the risk of
      long term welding.

PMID- 19839159
TI  - Rare combination of seven fractures in the same forearm and wrist.
AB  - A rare combination of a segmental ulnar fracture with fracture dislocation of the
      head of the radius and intraarticular fracture of the distal radius concomitant
      with an ipsilateral scaphoid, lunate and coronoid process fractures is presented.
      The mechanism of injury could possibly be a tremendous impact on the outstretched
      hand with a dorsiflexed wrist, fracturing the carpal bones and the distal radius.
      Transmitted axial forces on the ulna in a pronating forearm resulted in the other
      fractures. To the best of our knowledge, no such case has been reported. Open
      reduction with screw fixation of the scaphoid, plating of the proximal ulna and
      Kirschner wiring of the distal radius and radial head dislocation were done.

PMID- 19839160
TI  - Intussusception as a complication of gastrostomy tube: a case report.
AB  - A neurologically impaired child who had fundoplication and gastrostomy done for
      gastroesophageal at the age of three, presented two years later with intestinal
      obstruction. She underwent laparotomy and was found to have antegrade jejuno
      jejunal intussusception. Intussusception is an unusual but recognised
      complication of gastrostomy tube placement.

PMID- 19839161
TI  - Adenoid cystic carcinoma of the trachea: a case report.
AB  - A case report of adenoid cystic carcinoma of the trachea is presented. A high
      index of suspicion is required to make the diagnosis of tracheal tumours early
      since the patients tend to have normal chest radiographs which on closer
      examination may show an abnormality of the tracheal column. Adenoid cystic
      carcinoma is the most common malignant tumour of the trachea. Locoregional
      control of this disease is achieved by a combined modality therapy of surgery and
      postoperative radiotherapy. Despite this, it still has a prolonged clinical
      course and the tendency for delayed onset of distant metastases.

PMID- 19839162
TI  - Tretinoin in pregnancy complicated with acute promyelocytic leukaemia.
AB  - Acute promyelocytic leukemia (APL) in pregnancy poses serious danger to both the
      mother and fetus. Cytotoxic chemotherapy may cause teratogenicity to the fetus.
      APL is unique because it is usually associated with a coagulopathy that markedly
      increases the risk for the mother and fetus. A 21 year old lady with APL in her
      third trimester of pregnancy was treated with oral tretinoin. Tretinoin reversed
      the coagulopathy and normalised her blood counts without causing cytotoxic damage
      associated with cancer chemotherapy. Fetal distress occurred at 37 weeks of
      gestation and an emergency caesarean section was performed without complications
      and no blood transfusion support was needed as her coagulopathy and
      thrombocytopenia had resolved. A remission was achieved with only tretinoin
      induction. She subsequently had consolidation and maintenance chemotherapy. The
      mother and baby remain well at 4 years from completion of chemotherapy. A total
      of 10 pregnancies associated with APL have been reported in the current
      literature. Premature delivery and a fetal arrhythmia were the only
      complications. Although retinoin is considered teratogenic, its use so far in
      second and third trimester has been safe.

PMID- 19839163
TI  - Revisiting the obstetric flying squad.
AB  - The obstetric flying squad has been used in obstetric practice since 1933 to
      manage obstetric emergencies occurring in domicilliary practice. It has often
      been criticised in such situations as only delaying effective treatment to the
      patient. We have introduced the obstetric flying squad in an urban setting to
      cater for obstetric emergencies occurring in private practice. This service has
      been used on ten occasions since its inception without any maternal deaths being
      recorded or any delay in the provision of emergency care. The flying squad has
      led to closer cooperation between the government and private sectors in providing
      obstetric care.

PMID- 19839164
TI  - Bleomycin and oxytetracycline sclerotherapy for malignant pleural effusions.

PMID- 19839166
TI  - A diverse array of cosmetic topics.

PMID- 19839165
TI  - Current trends in the management of chronic obstructive pulmonary disease.

PMID- 19839167
TI  - Erbium:YAG laser resurfacing in patients with inflamed cystic acne.
AB  - BACKGROUND: Inflammatory cystic acne has been treated by a variety of modalities
      including antibiotics, topical agents, isotretinoin and chemical peels with
      variable degrees of success. Erbium:YAG lasers have been used for the treatment
      of acne scarring and photoaged skin but have not been thought of as treatment for
      actively inflamed lesions. OBJECTIVE: We sought to ascertain the effectiveness of
      using low fluence erbium:YAG settings without topical anesthesia for the
      treatment of two patients with inflamed cystic acne. METHODS: Two female patients
      with type 4 skin of Hispanic (32 years old) and south Asian (21 years old) origin
      were treated with the 2940 erbium:YAG LaserPeel laser. The Hispanic patient was
      treated twice with a 2-month interval between treatments using the 200 mJ
      setting. The Asian patient had a combination of 200 and 400 mJ settings for her
      first treatment and 400 mJ for the subsequent two treatments. She was treated
      three times with an interval of 1 month between the first two treatments and a 2
      month interval between the second and third treatments. RESULTS: Both patients
      healed within 6 days of each treatment and demonstrated progressive improvement.
      Results were excellent in both. CONCLUSION: Low fluence erbium:YAG facial
      resurfacing was effective for the treatment of inflamed cystic acne. Its use as a
      treatment modality should be further explored.

PMID- 19839168
TI  - Treatment of inflammatory facial acne vulgaris: comparison of the 1450-nm diode
      laser and conventional physical treatment.
AB  - The efficacy of the 1450-nm diode laser in the treatment of inflammatory facial
      acne was evaluated by comparing it with conventional physical treatment.
      Seventeen patients received laser treatment on the right side of the face and
      conventional physical treatment on the other side. The two modalities were
      compared through photographs, inflammatory acne lesion counts, and a patient
      questionnaire. Clinical response was evaluated in 16 patients. Evaluation of
      baseline and follow-up photographs indicated that more improvement was obtained
      after laser treatment than by physical treatment in six patients. In two
      patients, physical treatment yielded better results than laser treatment. Equal
      effect was obtained in eight patients. All patients had a reduction in the
      inflammatory acne lesion count on the laser-treated side, which was statistically
      significantly greater on the laser-treated side compared with the side treated
      physically (p=0.039, Wilcoxon signed ranks test). By the assessment of patient
      satisfaction, seven patients preferred laser treatment, two patients preferred
      physical treatment and three patients found laser treatment equal to physical
      treatment. Questionnaire details could not be obtained in 4 patients. This study
      indicates that the 1450-nm diode laser is a new option for local treatment of
      acne.

PMID- 19839169
TI  - Treatment of active acne with an Er:Glass (1.54 microm) laser: a 2-year follow-up
      study.
AB  - BACKGROUND: To investigate the effects of the 1.54 microm wavelength on active
      lesions of the face and of the back at the 2-year follow-up. METHODS: A 1.54
      microm erbium:glass laser (Aramis, Quantel Medical, France) was used in
      combination with contact cooling set at +5 degrees C to treat acne on the face
      with the following parameters (3 ms, four pulses, 10 J/cm2, 2 Hz, cumulative
      fluence: 40 J/cm2). The laser spots were adjacent (maximum overlap: 20%) and
      delivered in rows in order to cover the entire area. Four treatments were
      performed at 4-week intervals in 25 patients with acne severity greater than 3 on
      the Burton scale. Acne lesion counts (papules, pustules, nodules, comedones) were
      performed prior to each treatment, and at 2, 4, 12, 18 and 24 months after the
      final treatment. RESULTS: Among the 25 patients, three were lost to follow-up,
      four were retreated. So, 18 patients had acne lesions counts 2 years after the
      fourth treatment. The mean percent reduction was 71% at the 6-month follow-up,
      79% at the 1-year follow-up and 73% at the 2-year follow-up. No side effects were
      reported. All patients commented that their skin was less prone to oiliness.
      Biopsies taken after treatment showed progressive rarefaction and miniaturization
      of sebaceous glands and pilosebaceous follicles without morphologic damage to
      epidermal and dermal structures. CONCLUSION: Active acne can be successfully
      treated by selective dermal heating with a 1.54 microm erbium:glass laser coupled
      to contact cooling, with no related side effects. Furthermore, this longer follow
      up study demonstrates long-term acne clearing. Combined treatments with
      medications (oral or topical) or light (targeting Propionibacterium acnes) may
      also improve acne clearance.

PMID- 19839170
TI  - Cutaneous effects compared between higher fluence with fewer treatments and lower
      fluence with more treatments in a combined IR laser/radio frequency system.
AB  - BACKGROUND AND AIMS: A combined infrared (IR) laser/radio frequency (RF) system
      has recently been reported to create rejuvenation-related cutaneous effects, but
      was associated with high levels of pain and some complications. The present study
      was designed to evaluate the cutaneous effects of the same system with a lower
      fluence and more treatments. METHODS: Twenty patients were randomly assigned into
      two groups of 10 individuals each: Group A was treated at 50 J/cm2/100 J/cm3
      (laser/RF), respectively, two passes, three treatment sessions 30 days apart;
      Group B at 30 J/cm2/50 J/cm3, three passes, five treatment sessions 15 days
      apart. Objective comparisons were made at the same time points with a computer
      program based on the clinical photography. RESULTS: Group A noted more
      improvement in wrinkles than Group B at the first assessment, but both groups
      showed slight and progressive deterioration at the 2- and 6-month assessments.
      Improved skin appearance was maintained throughout in both groups. The authors
      recognize that the comparatively small number of subjects possibly limits the
      statistical power of the study. CONCLUSIONS: Lower fluences and more treatment
      sessions with the combined 900 nm laser/RF system were complication-free,
      produced improvements in the overall skin condition and less pain during
      sessions, suggesting that this combination may produce better patient compliance.
      Further treatment sessions may improve the results with implications in skin
      rejuvenation.

PMID- 19839171
TI  - Evaluation of the combination of radio frequency, infrared energy and mechanical
      rollers with suction to improve skin surface irregularities (cellulite) in a
      limited treatment area.
AB  - This IRB-approved (Institutional Review Board) study evaluated the efficacy of a
      device that combines radio frequency, infrared energy and mechanical
      rollers/suction (ELOS technology) to reduce skin surface irregularities in a
      limited treatment zone. Sixteen patients were enrolled and received two
      treatments per week for 4 consecutive weeks. Treatments were limited to a 20.53
      cm x 33.02 cm area of the posterior or lateral thigh and lasted for 15 minutes.
      Maximum machine settings were used for all but one individual at every treatment.
      Evaluations consisted of a patient questionnaire and photographic assessment of
      skin contour by three physicians at 3 and 6 months after the last session who
      were blind to the treatment each patient received. Physician evaluators
      determined that all patients were improved at both post-treatment periods. The
      average improvement at 3 and 6 months was 62% and 50%, respectively. All patients
      felt they were improved. One patient described the treatment as painful and
      required reduced treatment parameters after the initial treatment. Bruising
      within the treatment area was observed in five patients following the initial
      sessions but this did not alter the treatment protocol and did not occur in
      subsequent treatments. One patient had a superficial skin burn due to poor
      electrode contact that did not require corrective treatment.

PMID- 19839172
TI  - Comparison of a combination diode laser and radiofrequency device (Polaris) and a
      long-pulsed 1064-nm Nd:YAG laser (Lyra) on leg telangiectases. Histologic and
      immunohistochemical analysis.
AB  - INTRODUCTION: Several devices have been proposed for the treatment of leg
      telangiectases. For most of these devices the histologic changes induced in the
      dermis are not well characterized. MATERIALS AND METHODS: Three volunteers with
      class I-II red and blue 0.1-2.0 mm leg telangiectases were treated with the Lyra
      (Laserscope, San Jose, CA, USA) and the Polaris (Syneron Medical Ltd, Yokneam,
      Israel) devices to the left and right legs, respectively. Two 3-mm punches were
      taken from either site 7 days after treatment. The specimens were routinely
      processed and also stained for elastic tissue and collagen tissue. RESULTS: After
      treatment, specimens treated with both the Polaris and the Lyra showed
      intermediate-sized vessels with complete thrombosis and extensive hemorrhage in
      both the dermis and subcutis. The overlying epidermis also evidenced damage
      characterized as focal full-thickness necrosis. Special stains confirmed the
      damage to the vessels. All other skin structures were morphologically
      unremarkable. An average of 50-75% clinical clearing occurred using both
      modalities of a single treatment session. CONCLUSIONS: Our study confirms that
      both devices result in severe damage to small, intermediate-sized vessels, thus
      explaining the reported clinical improvement of leg telangiectases. The
      expression of hsp70 in the dermal vessels and overlying epidermis is consistent
      with a direct thermal effect delivered by either device.

PMID- 19839173
TI  - Laser complications: hair removal.
AB  - The increasing use of laser and light source-based hair removal techniques has
      led to not only an increased incidence of reported complications, but also to a
      better understanding of the cause of such complications. The objective of this
      article was to provide an understanding of the incidence and the etiology of
      complications following laser/light-based hair removal. In conclusion, almost all
      complications following laser/light-based hair removal techniques can be
      prevented with a thorough understanding of the thermally induced effect of such
      treatment on the hair follicle and epidermal melanin. Some newly described
      complications may have a variety of etiologic factors.

PMID- 19839174
TI  - Effects of age, task complexity, and exercise on reaction time of women during
      ambulation tasks.
AB  - PURPOSE: Reaction time (RT) is defined as the time lapse between the onset of a
      stimulus and the initiation of a response. The purpose of Study 1 was to compare
      RTs of young and elderly women during ambulation. The purpose of Study 2 was to
      investigate the effects of regular exercise on RTs of elderly women during
      ambulation tasks. METHODS: Reaction times were measured using a portable
      computer, 2 transistor radios, and a radio interface box. The computer generated
      an auditory signal to which participants reacted by pushing a hand-held switch.
      Reaction times were compared in Study 1 between 17 healthy elderly women and 13
      university students and in Study 2 between 15 exercising and 16 non-exercising
      elderly women. Testing of each participant occurred during sitting, walking on
      tile, and walking on foam padded carpet. RESULTS: The results of Study 1 revealed
      differences in RT between the 2 groups and between the sitting and the 2 walking
      conditions, but no interaction between group and task complexity. The results of
      Study 2 revealed differences among all conditions, but not between groups.
      CONCLUSIONS: The surprising result of Study 1 was that the elderly were not
      compromised to a greater extent than the young by increased task complexity. This
      suggests less age related RT decline during familiar activities. Results of Study
      2 showed that level of exercise did not differentiate elderly participants'
      performance on RT. This may be because the active lifestyle of both groups of
      participants was more important in maintaining RT than a formal exercise program.

PMID- 19839175
TI  - Normative values for the unipedal stance test with eyes open and closed.
AB  - PURPOSE: Limited normative data are available for the unipedal stance test
      (UPST), making it difficult for clinicians to use it confidently to detect subtle
      balance impairments. The purpose of this study was to generate normative values
      for repeated trials of the UPST with eyes opened and eyes closed across age
      groups and gender. METHODS: This prospective, mixed-model design was set in a
      tertiary care medical center. Healthy subjects (n= 549), 18 years or older,
      performed the UPST with eyes open and closed. Mean and best of 3 UPST times for
      males and females of 6 age groups (18-39, 40-49, 50-59, 60-69, 70-79, and 80+)
      were documented and inter-rater reliability was tested. RESULTS: There was a
      significant age dependent decrease in UPST time during both conditions. Inter
      rater reliability for the best of 3 trials was determined to be excellent with an
      intra-class correlation coefficient of 0.994 (95% confidence interval 0.989
      0.996) for eyes open and 0.998 (95% confidence interval 0.996-0.999) for eyes
      closed. CONCLUSIONS: This study adds to the understanding of typical performance
      on the UPST. Performance is age-specific and not related to gender. Clinicians
      now have more extensive normative values to which individuals can be compared.

PMID- 19839176
TI  - Age-related deterioration in flexibility is associated with health-related
      quality of life in nonagenarians.
AB  - BACKGROUND AND PURPOSE: Studies indicate that age is associated with
      deterioration in physical function and a concomitant decrease in health-related
      quality of life (HRQL). The contribution of physical function to HRQL in
      nonagenarians (ages 90-99) is unknown. The purposes of this study were to examine
      age-related changes in physical function and HRQL among community-dwelling
      nonagenarians and to determine the relationship between their physical function
      and HRQL. METHODS: Seventy-four community-dwelling nonagenarians participated.
      The Continuous Scale Physical Function Performance Test-10 (CS-PFP10) was used to
      measure their physical function and the Short Form (SF)-36 was used to measure
      their HRQL. Pearson correlations were used to assess associations among age,
      physical function, and HRQL scores. RESULTS: Age was inversely associated with
      the upper body flexibility (r = -.365, p = .001) subscale of the CS-PFP10, but
      not significantly associated with any other physical function or HRQL score.
      Significant associations between physical function and HRQL were limited to those
      between upper body flexibility and the physical function subscale (r = .424, p <
      .001) and physical function component summary score (r = .376, p = .001) of the
      SF-36. CONCLUSION: These data suggest that upper body flexibility continues to
      decline during the 10th decade of life and has implications for influence on
      aspects of HRQL in this segment of the population.

PMID- 19839177
TI  - Relationship of closed and open chain measures of strength with perceived
      physical function and mobility following unilateral total knee replacement.
AB  - BACKGROUND AND PURPOSE: The association between closed-chain knee extensor
      strength and perceived physical function following primary knee replacement has
      not received much attention.The purpose of this investigation was to determine
      the relationship of closed and open chain measures of strength with self-reported
      measures of physical function and mobility following unilateral knee replacement.
      METHODS: Subjects were 9 individuals (68. 7 +/- 2.3 years) approximately 16
      months postsurgery. The independent variables were closed-chain (elastic) and
      open-chain (isometric) measures of strength, while the dependent measures were
      perceived physical function (WOMAC) and mobility (Timed Up and Go, TUG). The
      relationship between independent and dependent variables was described using
      Spearman Rho correlation coefficients. RESULTS: Force produced during the closed
      chain assessment was strongly associated to the WOMAC physical function dimension
      (-.96) and total WOMAC score (-.87). A poor to low relationship existed between
      the open-chain measure of strength and the physical function dimension (-.34) and
      the total WOMAC score (-.17). Force production of the entire lower limb, measured
      in the closed-chain was moderately related (-.62) with the TUG. The association
      between knee extensor isometric torque and the TUG (-.25) was low. CONCLUSIONS:
      Closed-chain assessment of entire lower limb strength, rather than open-chain
      measures of knee extensor strength, may provide greater insight to functional
      limitations.

PMID- 19839178
TI  - Average grip strength: a meta-analysis of data obtained with a Jamar dynamometer
      from individuals 75 years or more of age.
AB  - BACKGROUND AND PURPOSE: Although strength diminishes with age, average values for
      grip strength have not been available heretofore for discrete strata after 75
      years. The purpose of this meta-analysis was to provide average values for the
      left and right hands of men and women 75-79, 80-84, 85-89, and 90-99 years.
      METHODS: Contributing to the analysis were 7 studies and 739 subjects with whom
      the Jamar dynamometer and standard procedures were employed. RESULTS: Based on
      the analysis, average values for the left and right hands of men and women in
      each age stratum were derived. CONCLUSIONS: The derived values can serve as a
      standard of comparison for individual patients. An individual whose grip strength
      is below the lower limit of the confidence intervals of each stratum can be
      confidently considered to have less than average grip strength.

PMID- 19839179
TI  - Efficacy of percutaneous vertebral augmentation and use of physical therapy
      intervention following vertebral compression fractures in older adults: a
      systematic review.
AB  - PURPOSE: The purpose of this systematic literature review was to summarize
      information on the efficacy of percutaneous vertebral augmentation (PVA) and the
      incorporation of physical therapy intervention following PVA for vertebral
      compression fractures (VCF). METHODS: Literature searches were completed using
      the Cochrane Library: Cochrane Database of Systematic Reviews (Cochrane Reviews);
      Agency for Healthcare Research and Quality (AHRQ): National Guideline
      Clearinghouse; Physiotherapy Evidence Database (PEDro); Medline; and Cumulative
      Index of Nursing and Allied Health Literature (CINAHL) through August 2005.
      RESULTS: Seventeen relevant studies were identified. They reported favorable
      outcomes (eg, earlier mobility, decreased pain, and improved spinal posture)
      after PVA. No study addressed physical therapy intervention after PVA.
      CONCLUSION: PVA appears to be an effective treatment option for individuals with
      VCF. However, research dealing with physical therapy after PVA is needed.

PMID- 19839180
TI  - [Long-term management of coronary patients: current guidelines and practices].
AB  - The management of coronary patients aims at improving the prognosis, by
      preventing myocardial infarction and/or death, and also at optimal reduction of
      symptoms related to coronary disease. This can be achieved by a variety of
      approaches including coronary revascularisation, life-style modifications and
      drug therapies including several drug classes: platelet inhibitors, beta
      blockers, angiotensin converting enzyme (ACE) inhibitors, statins and anti
      anginal drugs. The B.A.S.I.C. regimen is a combination of a beta-blocker, a
      platelet inhibitor, a statin and an ACE inhibitor for secondary prevention in
      coronary patients. Although recommended in the latest ESC and AHA/ACC guidelines,
      this strategy is insufficiently applied in medical practice. Indeed, the results
      of the European Action on Secondary Prevention by Intervention to Reduce Events
      (EUROASPIRE) Survey conducted over the period 1999-2000, show that 6 months after
      a first hospitalisation for aorto-coronary bypass, percutaneous coronary
      angioplasty, myocardial infarction or acute coronary syndrome, 86% of patients
      are prescribed a platelet inhibitor, 63% a beta-blocker, 61% a hypolipidaemic
      agent and only 38%, an ACE inhibitor. The PREVENIR Study published in 2005
      reported that only 12% of patients are prescribed the B.A.S.I.C. quadritherapy
      outside the acute phase. Despite recognised benefits in terms of survival, the
      B.A.S.I.C. approach is therefore clearly under-prescribed following coronary
      events.

PMID- 19839181
TI  - [Statins and antiplatelet agents: complementary mechanisms of action at the
      coronary artery level].
AB  - Atherothrombotic lesions associate atherosclerosis with a thrombotic reaction;
      they result from a complex inflammatory response to multifactorial stress.
      Endothelial dysfunction, lipid accumulation in the arterial intima, the
      recruitment of circulating monocytes and differentiation into macrophages and
      then foam cells, and an inflammatory reaction, all participate in the genesis of
      atheromatous plaque. The lipid core and fibrous parts of the plaque then
      contribute to its progression towards stenosis as a result of lipid infiltration,
      an accumulation of foam cells and the proliferation of smooth muscle cells with
      the synthesis of extracellular matrix. Atheromatous plaque is likely to rupture.
      The inflammatory components and an accumulation of cholesterol are two important
      characteristics found in the event of plaque rupture. The importance of the
      incorporation of thrombotic material formed during a silent rupture should also
      be emphasised. Among the factors favouring plaque rupture, a distinction can be
      made between extrinsic factors such as hypertension, and intrinsic factors which
      reflect the vulnerability of the plaque in terms of its quantitative aspects
      (relative composition in lipids and fibrous tissues) and qualitative
      characteristics (solidity of the fibrous cap and proteins in the extracellular
      matrix, the degradation of which is controlled by metalloproteinases). In the
      prevention of atherothrombosis-related complications, statins and platelet
      inhibitors have complementary mechanisms of action. Statins reduce inflammation,
      modify the composition of atheromatous plaque and promote stabilisation, while
      acetylsalicylic acid reduces the formation of thrombin, exerts an anti-thrombotic
      action, reduces endothelial dysfunction and the proliferation of vascular smooth
      muscle cells, and, like statins, has an anti-inflammatory effect. As a result, in
      the context of the B.A.S.I.C. strategy recommended by 2002-2003 ESC guidelines,
      the fixed statin-acetylsalicylic acid combination appears to constitute a logical
      combination in coronary patients in order to prevent the clinical complications
      linked to atherothrombosis.

PMID- 19839182
TI  - [Pravastatin and acetylsalycilic acid fixed-combination: a strategy to improve
      cardiovascular outcomes].
AB  - The rationale behind combined statin-acetylsalicylic acid therapy is based on the
      beneficial effects ofacetylsalicylic acid on thrombosis, the leading immediate
      cause of the majority of occlusive cardiovascular events, and those of statins on
      atherosclerosis, which is the main underlying cause. The clinical benefits of
      combined pravastatin-acetylsalicylic acid in the management of coronary patients
      have been demonstrated by a meta-analysis of five randomized clinical trials for
      secondary prevention; compared with pravastatin alone, the pravastatin
      acetylsalicylic acid combination reduced the risk of fatal or non fatal
      myocardial infarction by 26%, the risk of ischemic stroke by 31%, and the risk of
      cardiovascular events at 5 years by 13%. Combined pravastatin-acetylsalicylic
      acid therefore appears to significantly reduce the cardiovascular risk in
      coronary patients. Following the AHA/ACC and National Cholesterol Education
      Program (NCEP) I and II guidelines, the proportion of patients treated by
      acetylsalicylic acid, beta-blockers and statins increased significantly: 94%, 57%
      and 91% respectively at one year versus 68%, 18% and 10% before the guidelines
      were applied. The impact of these treatments on clinical outcomes is
      statistically significant in terms of recurrent myocardial infarction, the need
      for re-hospitalization, sudden death or all-cause mortality. Patients treated
      with combined statin-acetylsalicylic acid therapy have significantly improved
      clinical outcome and a significantly lower rate of coronary events at 1 year of
      follow-up. These data therefore confirm the importance of optimizing therapeutic
      management of coronary patients, and in particular with combined acetylsalicylic
      acid-statin therapy.

PMID- 19839183
TI  - [Optimizing long-term therapy: dawn of a new era].
AB  - The combination of a beta-blocker, a platelet inhibitor, a statin and an ACE
      inhibitor (B.A.S.I.C. regimen) provides major therapeutic benefits in the
      management of coronary patients. In patients receiving the quadruple combination,
      the overall mortality risk is 75% lower than for patients receiving none of these
      four therapies. According to the data from the PREVENIR III study, the
      combination of a statin and a platelet inhibitor reduces the risk of recurrent
      coronary events by 71%, the risk of recurrent vascular events by 65% and the risk
      of death from all causes taken together by 68%, when compared with the absence of
      these two medications. In the French USIC 2000 survey, prescription of the triple
      combination of platelet inhibitor, statin and beta-blocker is also associated
      with a 50% reduction in overall mortality. However, although the B.A.S.I.C.
      strategy is of major therapeutic value, it markedly increases the number of
      tablets to be taken every day. Treatment compliance, which is a predictive factor
      for overall mortality in diabetic coronary patients, diminishes markedly as the
      number of medications to be taken every day increases. The availability of fixed
      combinations, e.g. statin-acetylsalicylic acid, thus makes it possible to reduce
      the number of tablets to be taken at any one time, thus potentially increasing
      treatment compliance and the efficacy of the treatment administered.

PMID- 19839184
TI  - Mechanical effects of implant-tooth rigid connection by a fixed partial denture:
      a 3d finite element analysis.
AB  - This study investigated the mechanical behaviour of tooth-implant fixed partial
      dentures by three-dimensional Finite Element Analysis. Titanium implants of
      various length and diameter were rigidly connected to a premolar either by two
      connected ceramic crowns or by a three unit Fixed Partial Denture. The implant
      acted like the fulcrum of an orthodontic device inducing tooth intrusion. Bone
      stresses appeared around the neck of the implant. Implant and abutment's stresses
      were meaningfully less intense with high diameter and low span. Implant length
      was a less influencing parameter. The use of wide-bodied implants is recommended
      in selected cases of short-span fixed partial dentures.

PMID- 19839185
TI  - Effect of ferrule placement on the fracture strength of cyclically loaded bovine
      teeth restored with cemented cast post-cores and crowns.
AB  - This experiment investigated the effect of a ferrule on the strength and fracture
      resistance of bovine teeth restored with cemented cast post-cores and crowns,
      compared to crowns alone or to crowns over non-ferrule cores. Thirty restored
      bovine teeth were subjected to 4 x 1095) cycles from 20 N to 120 N at 10 Hz,
      followed by fracture testing. Crowns alone were weaker than post restored teeth.
      There was no difference in fracture strength between ferrule and non ferrule
      teeth restored with crowns. All of the fractured teeth were subsequently
      unrestorable. CONCLUSIONS: Fracture resistance was not enhanced by 2 mm ferrule
      height.

PMID- 19839186
TI  - Holographic stress analysis in a distal extension removable partial denture.
AB  - This study examines stress analysis of the mandible when submitted to mastication
      simulated forces over a distal extension removable partial denture. Two
      situations were analyzed upon loading: small pins had been placed over the bone
      crest and under the denture; low amplitude loads were applied over tooth 34-37.
      Holographic interferometry techniques were used to assess mandible's deformation.
      Results indicate that a correct adaptation of the denture base is critical to
      reduce stresses in the mandible. High stress levels in the second molar region
      suggest its non-inclusion in these prosthetic rehabilitations.

PMID- 19839187
TI  - Effects of storage media on physical properties of selected tooth coloured
      restorative materials.
AB  - It is known that storage media can affect the physical properties of some
      restorative dental materials. The purpose of this laboratory study was to
      investigate the possible effects of storage media on physical properties of a
      conventional glass-ionomer, a resin modified glass ionomer and a compomer.
      Specimens of the restorative materials in the study (FujiII LC, FujiIX and Dyract
      EXTRA) were prepared. The specimens were stored in either water or artificial
      saliva with or without exposure to Listerine. The compressive and diametral
      tensile strength and Vickers hardness of these materials were tested at 24 hours,
      1 week, 4 weeks and 12 weeks. Compressive and diametral tensile strength for
      FujiII LC and Fuji IX had increased at 12 weeks. A decrease was observed for
      Dyract EXTRA in the same period. No significant differences were observed between
      the storage media (P > 0.01). Vickers hardness values fluctuated during the
      testing period, with a pattern being consistent for each material. Storage of
      materials investigated for the period in this study resulted in superior
      compressive and diametral tensile strength for Fuji II LC and FujiIX. The
      opposite was true for Dyract EXTRA. Effects of time were found to be more
      pronounced than the media (P < 0.01).

PMID- 19839188
TI  - Evaluation of the antimicrobial activity and dimensional alterations of alginate
      impression disinfectants.
AB  - This paper offers a quantitative evaluation of the antimicrobial efficacy of
      eight different disinfection procedures for irreversible hydrocolloid impressions
      and the dimensional changes induced by them. Samples were collected immediately
      after impressions, after the disinfection procedures and over casts and analyzed
      for bacterial growth. Control, enzyme solutions, acetic acid and ultraviolet
      irradiation samples showed bacterial growth. Chlorhexidine and 1% sodium
      hypochlorite presented adequate antimicrobial activity, while 2% sodium
      hypochlorite solution showed the best results. Dimensional changes were similar
      to those of the controls in all the tested agents. The results indicated 2%
      hypochlorite was the most appropriate disinfectant tested.

PMID- 19839189
TI  - Three-dimensional finite element analysis of the effect of incomplete seating of
      cemented fixed dental prostheses.
AB  - This study investigated the stress distribution patterns of two finite element
      models of a stylized fixed dental prosthesis-cement-abutment tooth system, one
      with the prosthesis completely seated and the other manipulated to be
      incompletely seated. Maximum equivalent von Mises stress varied according to
      direction and location of load, with vertical loading of the pontic of the
      completely-seated FDP (2.9 MPa) and oblique loading of the premolar of the
      incompletely-seated FDP (80.8 MPa) producing the least and the highest values,
      respectively. Total deformation of the restored system showed variations,
      although different cements had minimal effect on stress and on deformation. Under
      the conditions studied, a fixed dental prosthesis that had not been verified as
      fully seated on its abutments prior to cementation, could, with repeated loading
      cycles, be predicted to suffer a greater risk of fatigue, and thus clinical
      failure.

PMID- 19839190
TI  - Bonding auto-polymerising acrylic resin to acrylic denture teeth.
AB  - This study investigated the effect of surface treatments on the shear bond
      strength of an auto-polymerising acrylic resin cured to acrylic denture teeth.
      The surface treatments included a combination of grit-blasting and/or wetting the
      surface with monomer. Samples were prepared and then stored in water prior to
      shear testing. The results indicated that the application of monomer to the
      surface prior to bonding did not influence the bond strength. Grit blasting was
      found to significantly increase the bond strength.

PMID- 19839191
TI  - [Respiratory tract symptoms and illnesses in rescue and clearance workers after
      the World Trade Center catastrophe].
AB  - The World Trade Center catastrophe and subsequent rescue and clearance operations
      caused unusual respiratory tract symptoms in fire fighters and rescue workers.
      Persistent cough was a common symptom, being extraordinarily often associated
      with the gastroesophageal reflux symptom. Irritant dusts caused reactive airways
      dysfunction syndrome (RADS). Tracheal hyperreactivity increased with the
      exposure, and the risk of asthma is estimated to have increased up to 12 times
      higher as compared with the normal population. Investigation and treatment of
      exposed persons have yielded generalizable information about the reactions of the
      respiratory system in situations of heavy exposure.

PMID- 19839192
TI  - [EEG examination in emergency medicine and analysis of unconciousness].
AB  - For a long time, the EEG examination has been used as a laboratory examination
      especially in the diagnostics of epilepsy, but both technical difficulties and
      problems in interpretation have limited its use in emergency medicine outside
      special neurological intensive care units. Development of monitoring technology
      and easier data transfer is making EEG monitoring possible also in the emergency
      area. The greatest need focuses on the diagnostics and treatment of status
      epilepticus underlying an unclear unconsciousness. In other indications the
      usually required information can be obtained by daytime measurements.

PMID- 19839193
TI  - ["Tennis leg"--calf muscle rupture of the middle-aged tennis aficionado].
AB  - During tennis, the patient heard a bang from his left calf. The inferior edge of
      the calf muscle at the musculotendinous junction of the medial branch of m.
      gastrocnemius was tender to pressure, indicating a rupture called as "tennis
      leg". Foot movements are usually normal, but moving about is painful. The finding
      is confirmed by ultrasonography. First aid will limit the injury, and when the
      pain allows, active exercise therapy is initiated. Healing occurs in 2 to 6
      weeks, the more difficult ones in 3 to 4 months. Return to the court may take
      place gradually with a bandaged calf.

PMID- 19839194
TI  - [Update on current care guidelines. Depression, current care guideline].
AB  - The treatment of depression is based on careful diagnostic evaluation. In the
      acute phase of treatment, brief psychotherapies (cognitive, interpersonal,
      psychodynamic or problem-solving) are effective in cases of mild to moderate
      depression. Antidepressants are also effective, their importance increasing
      alongside the level of severity. Electroconvulsive therapy (ECT) is effective for
      severe or psychotic depression. After the acute phase, antidepressants must be
      continued for at least six months to prevent a relapse; maintenance
      antidepressant treatment must be considered after three lifetime episodes.
      Primary health care is responsible for the majority of mild to moderate cases of
      depression, but psychiatric consultation services and nurse case managers are
      required to fulfill this task.

PMID- 19839195
TI  - [Post-traumatic stress disorder].
AB  - Psychosocial support and careful monitoring are recommended for acute stress
      reaction (ASR) and acute stress disorder (ASD). If symptoms require, short
      focused cognitive-behavioural psychotherapy can be used for ASD. Medication is
      rarely necessary, but sleeping pills can be used for a short period. Trauma
      focused psychotherapeutic interventions are first-line treatment for post
      traumatic stress disorder. SSRI or SNRI antidepressant medication is also
      effective. There is less evidence on antipsychotic and antiepileptic medication.
      Psychotherapeutic interventions and medication can be, and often are, combined.
      Children, the elderly, and military and peacekeeping personnel need interventions
      that are tailored to their needs.

PMID- 19839196
TI  - [Why does a person become depressed?].
AB  - Genotype, temperament, early traumas, ongoing stress as well as the their mutual,
      cumulative effects are factors predisposing to depression. Depressed patients
      often have minor structural lesions of the brain, and during the depressive state
      they exhibit both neurochemical abnormalities and plasticity, metabolic activity
      and neuroendocrinological abnormalities of the brain. For the most part, these
      will return to normal with the convalescence. A temperament predisposing to
      depression may be reflected in functional imaging studies of the brain. The
      depressive state is usually triggered by a negative life event.

PMID- 19839197
TI  - [Neural plasticity and recovery from depression].
AB  - The brain processes information and emotions in neural networks, the plasticity
      of which has been proposed to be connected with the recovery from depression and
      mechanisms of action of antidepressants. Recent research results indicate that
      antidepressant therapy renews the neural network that has become misformed during
      development, if the formation of the network is simultaneously directed by
      rehabilitation. The pharmacological and psychological treatment modalities thus
      intermingle more closely than previously thought. The therapy for depression
      should aim to optimize the combined effects of different forms of therapy thus
      obtaining the highest efficacy from them.

PMID- 19839198
TI  - [Psychotherapy of a depressed patient--presentation of treatment modalities].
AB  - The article includes a brief introduction to five forms of psychotherapy that are
      in active use in Finland: psychodynamic, cognitive and group psychotherapy,
      family therapy of a depressed patient, and resource and solution-oriented working
      attitude. An advocate of each treatment modality provides a description of the
      suitability of the particular modality for a depressed patient. Different
      treatment modalities are not compared as such; the aim is rather to provide
      clinical thinking tools for the doctor, who considers the patient's suitability
      for and referral to psychotherapy.

PMID- 19839199
TI  - [When an antidepressant helps too much].
AB  - Initiation of an antidepressant may result in hypomania or mania. The risk is
      lower with selective serotonin reuptake inhibitors and bupropione than with
      venlafaxine and tricyclic antidepressants. With a mood-stabilizing medication,
      the risk of hypomania or mania will remain very low, along with its
      correspondingly lower efficacy. The therapy involves discontinuation of the
      antidepressant, initiation or dose elevation of a maintenance drug preventing
      hypomania and mania, and when needed, short-course use of a second generation
      antipsychotic.

PMID- 19839200
TI  - [Suicide mortality in Finland, 1947-2006].
AB  - BACKGROUND: Suicide mortality tends to vary in a population. The aim of this
      study was to find the turning points, if any, in suicide mortality in Finland in
      1947-2006. MATERIAL AND METHODS: Data on 64,483 deaths from suicide over the 60
      year period were obtained from Statistics Finland. Structural changing points
      were estimated by using multiple regression models. RESULTS: In 1955-1959 suicide
      mortality turned into worse for women. For men the turning point to worse was in
      1968-1974 and to better in 1987-1995. CONCLUSIONS: Continuous work and research
      is needed to enhance suicide prevention at regional level.

PMID- 19839201
TI  - [Outlook for patients by means of Health Technology Assessment].

PMID- 19839202
TI  - [Methodological standards for cost-of-illness studies using breast cancer,
      prostate cancer and colon cancer as an example].
AB  - Malignant neoplasia in mammary gland, prostate and colon appear at the top end of
      the cancer incidence and mortality statistics in Germany. In this context cost-of
      illness studies are a suitable tool for quantifying disease-specific health
      economic consequences of disease. Their primary aim is to illustrate the economic
      burden of a specific disease and its implications for society and for the
      national economy. The present review summarizes the methods and results of cost
      of-illness studies regarding the three cancer diseases mentioned. Despite some
      limitations and remarkable differences in respect of methodological aspects, it
      is possible to point out that numerous studies lead to similar results. For all
      three kinds of cancer, there is sufficient evidence to suggest that mainly
      initial and terminal states of disease are important, due to the major resource
      utilization caused by the claim of initial and palliative therapies. Inpatient
      costs--caused by the high rate of hospitalisation--account for 50% to 98% of the
      direct costs. As regards the societal perspective, a comparison of the three
      diseases considered demonstrates that especially the costs associated with breast
      cancer present a big challenge to the health care systems, which is primarily due
      to the high incidence rate in women under 65 years of age and the correspondingly
      high indirect costs resulting from invalidity, invalidity pensions or premature
      death. Future tasks to work on include analyzing the different patterns of health
      service utilisation and identifying the cost effects of different influencing
      factors. Transparency of costs, as a basis for cost-effectiveness analyses, could
      help to make interventions more precise.

PMID- 19839203
TI  - [Systematic literature research for Health Technology Assessment-related quality
      concerns with regard to medical documentation and information].

PMID- 19839204
TI  - [Prognostic value and clinical effectiveness of high sensitivity C-reactive
      protein as a marker in primary prevention of major cardiac events].
AB  - OBJECTIVE: To compare the predictive value and the clinical effectiveness of
      additional high sensitivity C-reactive protein (hs-CRP) screening as opposed to
      traditional risk factor screening alone as a strategy of primary prevention of
      coronary artery disease (CAD). METHODS: Following a comprehensive search of 26
      electronic databases by DAHTA DIMDI, a systematic review was performed in
      accordance with international standards of evidence based medicine. Eight
      publications on risk prediction and one study addressing clinical decision
      analytic modelling were included in the assessment. RESULTS: The adjusted
      relative risk of a high hs-CRP level (> 3 mg/L) for myocardial infarction,
      cardiac related death, and cardiovascular events ranged from 0.7 to 2.47 (p <
      0.05 in 4 of 7 studies). The area under the receiver operating characteristic
      curve (AUC) increased by 0.00 to 0.027 when hs-CRP was added to the prediction
      models (4 of 7 studies statistically significant with p < 0.05). Based on a
      published decision-analytic model examining hs-CRP screening, the gain in life
      expectancy due to statin therapy in individuals with elevated hs-CRP was similar
      when compared to patients with hyperlipidaemia. Nonetheless, evidence on many
      model parameters was limited. CONCLUSION: Screening with hs-CRP in addition to
      traditional risk factors improves risk prediction. However, the incremental
      effect is moderate and the clinical relevance remains unclear.

PMID- 19839205
TI  - [Intravascular brachytherapy for peripheral arterial occlusive disease:
      systematic review of medical efficacy and health economic modelling].
AB  - CONTEXT: Percutaneous transluminal angioplasties (PTA) using balloon dilatation
      with or without stenting are performed to treat peripheral arterial occlusive
      disease (PAOD). Intravascular brachytherapy (IB) after PTA promises to reduce the
      restenosis rates. The present article addresses questions concerning medical
      efficacy and cost-effectiveness of IB in PAOD patients. METHODS: A systematic
      literature search for randomized controlled studies evaluating IB in PAOD was
      conducted in August 2007. Information synthesis was conducted using meta
      analysis. Health economic modelling was performed on the basis of clinical
      assumptions derived from the meta-analysis and economical assumptions derived
      from the German Diagnosis Related Groups (G-DRG) 2007. RESULTS: Twelve
      publications covering seven studies about IB vs. no IB were included in the
      evaluation. IB after successful balloon dilatation showed a significant reduction
      in the rate of restenosis at six and/or twelve months (relative risk 0.62; 95%
      confidence interval: 0.46 to 0.84) and a significant delay in the time to
      recurrence of restenosis (17.5 vs. 7.4 months, p < 0.01). IB after stenting did
      not lead to significant results regarding the restenosis rates, but was more
      often associated with early and late occlusive thromboses. The incremental cost
      effectiveness ratio per restenosis avoided for IB vs. no IB after successful
      balloon dilatation was--depending on the G-DRG used-Euro 8,484 and Euro 9,058,
      respectively. In the comparison of IB vs. no IB after stenting IB was
      demonstrated to be inferior to no IB. CONCLUSIONS: IB after successful balloon
      dilatation in PAOD can be recommended from a medical point of view. From the
      health economic perspective the answer is not yet clear. IB after stenting in
      PAOD cannot be recommended.

PMID- 19839206
TI  - [Development and institutionalization of Health Technology Assessment in Austria:
      the Ludwig Boltzmann Institute for Health Technology Assessment].

PMID- 19839207
TI  - [Symposium for Health Technology Assessment: patients in no-man's-land].

PMID- 19839208
TI  - [Responsibility of student productivity in care-giving].

PMID- 19839209
TI  - [Transferability of clinical trials results into clinical practice: examples
      taken from cardiology].
AB  - A prospective and randomized trial design is of utmost interest when it comes to
      evaluating new developments in the management of cardiovascular medicine. By
      defining the primary end point and a profound related statistic new therapeutic
      options can be tested with an adequate number of patients. The course of the
      trial is supervised by a Clinical Events Committee and a Data and Safety
      Monitoring Board. Registries are promising tools for describing how the results
      of clinical trials are translated into daily practice. Their drawbacks include
      lack of control of the clinical endpoints and their uniform definition and lack
      of a control group. There are numerous examples from cardiology of the limited
      usefulness of data obtained from registry studies with their often unexpected
      results that might have significant but unsubstantiated implications for the
      provision of care to cardiac patients.

PMID- 19839210
TI  - [Transferability of trial results into clinical practice: examples taken from
      paediatric practice].
AB  - Since 2000 there has been sufficient evidence that chest X-rays are unnecessary
      in infants and children with uncomplicated lower respiratory tract infection. The
      reason is that neither the diagnosis nor the first therapeutic decisions will be
      influenced by the result of this procedure, and especially so if children have
      been infected with the respiratory syncytial virus. However, epidemiological
      studies in Germany reveal an ongoing use of chest X-ray in these cases. This
      might suggest that the X-ray images are taken as "proof" of pneumonia, which
      indeed pays off in the German DRG (Diagnosis Related Groups) system since
      hospitals receive a higher reimbursement for RSV pneumonia than for RSV
      bronchiolitis.

PMID- 19839211
TI  - [Can the results of clinical trials of pharmacological interventions be
      transferred into everyday clinical practice?].
AB  - Transferability of results originating from randomized, controlled clinical
      trials is characterized by their external validity. Clinical trials are
      experimental in their design and conducted under standardized terms, that is,
      rigorous inclusion and exclusion criteria as well as an artificial trial
      environment may hamper the transferability of results. Studies designed for
      approval of new medicines usually exclude elderly patients, multi-morbid
      patients, pregnant women and children. For example, the median age at diagnosis
      of colorectal cancer in Germany is 69 (men) and 75 (women) years, respectively.
      In clinical trials investigating chemotherapy, however, patients above the age of
      70 years represent only 18% of the trial population. In cardiovascular trials,
      especially on acute coronary syndromes, women are usually under-represented.
      Guidelines derived from clinical trials should therefore explicitly mention a
      study's limitations. It should be communicated clearly for which patients and
      under which conditions the guideline is applicable.

PMID- 19839212
TI  - [Transferabilty of study results in routine health care: non-pharmacological
      interventions (surgery)].
AB  - In surgery, too, randomized clinical trials (RCTs) are the scientific method of
      choice for proving the effectiveness of a new intervention or the superiority of
      an innovative technique over an established one. However, there are particular
      challenges in surgical studies regarding the equality of structure, of treatments
      and observation in the study groups. The design of valid study protocols in
      surgery is very complex, which is the reason for the relatively small number of
      high-quality RCTs in surgical literature. Pragmatic studies offer a promising
      approach to the implementation of surgical innovations in health care. The German
      Society of Surgeons supports the conduct of multicentre clinical studies by
      providing the relevant structures (study centre, multicentre network CHIR-Net).
      Good clinical and comparative health care effectiveness research in surgery also
      needs stronger academic appreciation as a career incentive for young academic
      surgeons.

PMID- 19839213
TI  - [Joint discussion of the short report on problem solving: summary of the
      speeches].

PMID- 19839214
TI  - [Transferability of study results to health care practice: contribution of
      different qualitative and quantitative research approaches].
AB  - Along with the growing number of clinical and epidemiological studies the
      diversity of methodological approaches increases to an extent that many
      physicians and their patients experience as confusing. Should we not simplify
      matters by limiting our view to high-quality studies of evidence class 1 and
      ignore all the other approaches? In fact, the generation of evidence and a
      scientific understanding of real-world processes would be less successful if we
      forewent alternative approaches to randomized studies. While it is certainly true
      that direct proof of therapeutic efficacy can only be accomplished with high
      standard randomized trials, non-randomized studies contribute substantially to
      exploration, to the generation of hypotheses and to the assessment of the
      transferability of study results to routine health care practice. Moreover, for
      clinical decision-making and assessment of the expected individual therapeutic
      benefit physicians and their patients in several regards need additional
      information that usually cannot be derived from randomized trials such as to the
      natural course of the disease without the specific treatment, safety and quality
      of life aspects as well as disease concepts. Should the findings obtained from
      non-randomized studies not likewise be incorporated into the general assessment
      of therapeutic benefit within a population as conducted by the German Institute
      for Quality and Efficiency in Health Care (IQWiG) for different therapeutic
      approaches? Therapeutic processes could benefit most from research if randomized
      trials, cohort studies and registers were integrated and interconnected. This
      way, assessments of transferability will have a solid empirical base.

PMID- 19839215
TI  - [Discussion of the introductory hearings. Part 1: Subsequent to the delivery of
      the speech by Professor Wegscheider].

PMID- 19839216
TI  - [GRADE: from grading the evidence to developing recommendations. A description of
      the system and a proposal regarding the transferability of the results of
      clinical research to clinical practice].
AB  - The Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      working group represents an international collaboration of guideline developers,
      clinicians, health services researchers and methodologists. Many leading
      organizations, including the World Health Organization (WHO), use the GRADE
      approach because it has led to progress in the assessment of evidence and in the
      development of healthcare recommendations. The GRADE system distinguishes the
      quality of evidence from the strength of a recommendation. The quality of
      evidence reflects the extent of confidence that an estimate of effect is correct
      if it is used in the context of single endpoints. In the context of giving
      guidance, it reflects the extent to which confidence in an estimate of the effect
      is adequate to support recommendations. The strength of a recommendation,
      separated into strong and weak or conditional recommendations for or against an
      intervention, is defined as the extent to which one can be confident that the
      desirable effects of an intervention outweigh the undesirable effects. A
      recommendation for action requires consideration for the magnitude of the
      expected benefit and downsides of an intervention for all patient-important
      endpoints, the associate values and preferences and resource use. The GRADE
      system includes a systematic approach to evaluate the generalizability of study
      results to healthcare practice. Judgments about generalizability, better termed
      directness, are separated into judgments about the availability of direct
      comparisons between two alternative management strategies and judgments about
      differences between the population, intervention, comparator to the intervention,
      and outcomes (PICO) of interest for a given question, and those included in the
      relevant studies. In addition to providing an overview of the GRADE system, this
      article focuses on the approach to assessing directness or generalizability.

PMID- 19839217
TI  - [Discussion on the introductory hearings. Part 2: Following the speech of
      Professor Schunemann].

PMID- 19839218
TI  - [Pragmatic trials in a routine care setting].
AB  - Within clinical research the spectrum of possible trial objectives and designs
      ranges from explanatory to pragmatic. Pragmatic trials improve the knowledge base
      for clinicians, patients, regulatory and funding bodies as well as manufacturers
      of medical products. However, the pragmatic design has certain limitations and
      the assessment of external validity requires a considerable amount of judgment.
      Investigators need special expertise to conduct this kind of studies.

PMID- 19839219
TI  - [Discussion on the introductory hearings. Part 3: Following the speech of
      Professor Donner-Banzhoff].

PMID- 19839220
TI  - [Assessment of the generalisability of clinical trial results in the Federal
      Joint Committee].
AB  - The assessment of the transferability, sometimes called external validity, of
      study results is subordinate to the assessment of the internal validity of
      clinical studies. Although internal and external validity seem to be related they
      actually are fundamentally different concepts. While assessing the
      transferability or generalisability of study results effect-modifying factors
      (e.g., age, gender, qualification of the suppliers, technical equipment) have to
      be considered. In principle relevant or known effect-modifying factors can be
      allowed for within the decisions of the Federal Joint Committee (G-BA). This can
      be demonstrated by the example of acupuncture for chronic low back pain or
      osteoarthritis of the knee. However, the correct utilisation (and accordingly,
      effectiveness) of health technologies in everyday practice cannot be influenced
      by the G-BA. Still it would be desirable to have a scientifically sound,
      standardised tool available for assessing the external validity of study results.

PMID- 19839221
TI  - [Discussion on the introductory hearings on the usefulness and judgment].

PMID- 19839222
TI  - Antimicrobial pomegranate rind extracts: enhancement by Cu(II) and vitamin C
      combinations against clinical isolates of Pseudomonas aeruginosa.
AB  - Recently, natural products have been further evaluated as sources of
      antimicrobial agents with efficacies against a variety of microorganisms. This
      study reports the antimicrobial activities of pomegranate rind extract (PRE) in
      combination with Fe(II) and Cu(II) salts against extended-spectrum multidrug
      resistant Pseudomonas aeruginosa. Antimicrobial suspension assays were carried
      out using aqueous extract of pomegranate alone or in combination with metals
      salts against P. aeruginosa. The extract:metal salt combination was also enhanced
      with the addition of vitamin C. Marked activities were observed for the aqueous
      PRE/Cu(II) preparations, which were greatly enhanced by the addition of the
      reductant vitamin C. In contrast, the aqueous PRE/Fe(II) preparations were
      inactive, regardless of addition of vitamin C. The combination of PRE and Cu(II)
      salts and vitamin C showed the greatest activity against clinical isolates of P.
      aeruginosa. These results warrant further investigation of PRE as a potential
      source of new antimicrobial agents.

PMID- 19839223
TI  - Role of Helicobacter pylori in refractory iron deficiency anaemia.
AB  - The role of Helicobacter pylori infection in the development of iron deficiency
      anaemia has been the focus of attention over the past decade. However,
      confirmation of a relationship has not confirmed the pathophysiological
      mechanisms involved in the phenomenon. The aim of the present work is to study
      the levels of fasting gastric acidity (free and total) as well as the level of
      tumour necrosis factor-alpha (TNF alpha) in male refractory iron deficiency
      anaemia patients seropositive for H. pylori infection versus those who are
      seronegative. Thirty adult patients with iron deficiency anaemia and
      gastroduodenitis were subdivided into two groups of matched age and haemoglobin
      value. Group 1 was H. pylori-seropositive for infection and these patients did
      not receive prior treatment for eradication of H. pylori infection. Group 2
      comprised patients seronegative for H. pylori infection (control group). Patients
      with active bleeding or previous medical problems were excluded from the study.
      All patients and controls were subjected to the following at presentation:
      history taking and thorough clinical examination, complete blood picture,
      reticulocytes (%), assessment of serum iron, total iron binding capacity, serum
      ferritin, IgG anti-Helicobacter antibody and TNF alpha, stool for occult blood
      and measurement of gastric acidity (total and free). Upper endoscopy was
      performed and multiple biopsies were taken and tested for expression of cytotoxin
      associated gene A (cagA) by the polymerase chain reaction (PCR). Results showed
      significantly higher values of free and total gastric acidity as well as TNF
      alpha levels in Group 1 compared to controls (Group 2). Among those in Group 1,
      higher TNF alpha levels were seen in seven H. pylori cagA-positive patients than
      in eight cagA-negative patients. Haemoglobin values were inversely correlated
      with TNF alpha levels. Thus, elevated serum TNF alpha in the H. pylori
      seropositive group may be one of the underlying pathophysiological mechanism for
      iron deficiency anaemia observed in these patients.

PMID- 19839224
TI  - Low prevalence of the intact cag pathogenicity island in clinical isolates of
      Helicobacter pylori in Karachi, Pakistan.
AB  - Clinical diseases that follow Helicobacter pylori infection are associated with
      expression of the cagA gene, a part of cytotoxin-associated gene pathogenicity
      island (cag-PAI). This study aims to determined whether or not the presence of
      cagA is associated with the presence of complete cag-PAI and to evaluate
      inflammatory changes associated with the five loci in the cag-PAI of H. pylori
      comprising cagA, cagA promoter region (cagAP), cagE, cagT and the left end of the
      cagA gene (LEC). H. pylori isolates were obtained from patients with dyspeptic
      symptoms. Clinical strains of H. pylori were screened by the polymerase chain
      reaction (PCR) for respective genes of the cag-PAI. Of 115 H. pylori isolates, 31
      (28%) were positive for the five cag-PAI loci. H. pylori isolates with intact cag
      PAI were associated with gastric carcinoma (GC; n=9 [60%]) and gastric ulcer (GU;
      n=5 [45%]) compared to non-ulcer dyspepsia (NUD; n=14 [18%]) (P=0.001 and
      P=0.049, respectively). In patients with intact cag-PAI, acute on chronic
      inflammation was present in 25 (81%) and was more common than chronic
      inflammation (P=0.013). The cagE and cagAP had deletions in 25 (37%) and 23 (35%)
      cases, respectively. The cagAP region was significantly associated with GC (n=12
      [80%], P<0.001) and GU (n=9 [82%], P=0.001) compared to NUD (n=24 [30%] and with
      significant acute on chronic inflammation (n=40 [80%], P=0.007). The distribution
      of vacAs1a with intact cag-PAI in GC was 9 (60%) and in NUD was 10 (13%)
      (P<0.001). The presence of the cagA gene does not signify presence of an intact
      cag-PAI. Most of the H. pylori isolates studied had partial cag-PAI with missing
      cagE and cagA promoter regions.

PMID- 19839225
TI  - Evaluation of some markers of subclinical atherosclerosis in Egyptian young adult
      males with abdominal obesity.
AB  - Young adults with abdominal obesity are liable to have subclinical
      atherosclerosis that may contribute to an increased risk of cardiovascular
      disease later in life. This study aims to evaluate subclinical atherosclerosis
      and its possible correlation with some inflammatory and biochemical markers in
      Egyptian young adult males with abdominal obesity. The study includes 50 young
      adult males (age range: 19-29 years) divided into two groups. Group 1 comprises
      20 non-obese subjects (controls). Group 2 comprises 30 apparently healthy obese
      subjects. Carotid intima media thickness (carotid-IMT) was estimated using B-mode
      ultrasonography of the common carotid arteries, and abdominal ultrasonography was
      performed to assess the presence of a fatty liver. Laboratory investigations
      included fasting levels of serum glucose, triglycerides (TG), cholesterol (total
      [TC], high-density [HDL-cholesterol] and low-density [LDL-cholesterol]
      lipoprotein fractions), high-sensitivity C-reactive protein (hs-CRP), neopterin,
      lipoprotein-a (Lp[a]), gamma glutamyl transferase (GGT), aspartate and alanine
      aminotransferases (AST, ALT), plasma plasminogen and fibrinogen. Results showed
      that carotid IMT, serum hs-CRP, neopterin, Lp(a), fibrinogen, plasminogen, TC,
      TG, LDL-cholesterol and liver enzymes were significantly elevated (P<0.001) in
      the obese group compared to controls. All obese subjects showed evidence of fatty
      liver. A significant positive correlation was found between carotid-IMT and body
      mass index, waist circumference, waist/hip ratio, cholesterol, triglycerides,
      neopterin, hs-CRP AST, ALT and GGT. Elevated serum levels of inflammatory
      biomarkers and increased ALT, AST and GGT, and non-alcoholic fatty liver disease
      biomarkers may be useful predictors of subclinical atherosclerosis.

PMID- 19839226
TI  - Oxygen delivery index in homozygous sickle cell disease: steady and crisis
      states.
AB  - One of the common complications of sickle cell disease is the vaso-occlusive
      crisis or sickle cell crisis which could result in impaired oxygen delivery to
      the tissues. This study investigates the oxygen delivery index (ODI) in 38
      patients with homozygous sickle cell anaemia. Thirty-three patients were in the
      steady state and five were experiencing crisis at the time of recruitment. Whole
      blood viscosity was measured with a Wells Brookfield viscometer at a shear rate
      of 230 sec(-1) and haematocrit was measured with an AC Tron Coulter Counter. The
      ODI, which is an indirect measure of the capacity of blood to deliver oxygen to
      tissues, was calculated as the ratio of haematocrit to whole blood viscosity
      values. There was no statistically significant difference in the ODI between the
      steady and crisis states, suggesting that tissue oxygenation is not the only
      factor involved in the sickle cell crisis.

PMID- 19839227
TI  - Development of a novel immunoassay for the iron regulatory peptide hepcidin.
AB  - To date there have been few published immunoassays for the important iron
      regulator hepcidin. This study describes a novel competitive radioimmunoassay
      (RIA) for the bioactive hepcidin peptide. A rabbit anti-hepcidin polyclonal
      antibody was produced using synthetic hepcidin radiolabelled with 125I to produce
      a competitive RIA. Normal patient (n=47) samples were collected and assayed for
      hepcidin to determine a reference range. Other patient groups collected were
      ulcerative colitis (UC; n=40), iron deficiency anaemia (IDA; n=15), chronic
      kidney disease not requiring dialysis (CKD; n=45) and chronic kidney disease
      requiring dialysis (HCKD; n=94). Detection limit of the assay was determined as
      0.6 ng/mL. Intra-assay precision was 5 ng/mL (7.2%) and 50 ng/mL (5.8%),
      interassay precision was 5 ng/mL (7.6%) and 50 ng/mL (6.7%). Analytical recovery
      was 98% (5 ng/mL), 94% (10 ng/mL) and 97% (50 ng/mL). The assay was linear up to
      200 ng/mL. No demonstrable cross-reactivity with human insulin, glucagon I,
      angiotensinogen I, beta-defensin 1-4, alpha-defensin-1 and plectasin was
      observed. There was significant correlation (r=0.96, P < or = 0.0001) between the
      hepcidin RIA and an established hepcidin SELDI-TOF-MS method. Analysis of the
      normal human samples gave a reference range of 1.1-55 ng/mL for hepcidin. Further
      statistical evaluation revealed a significant difference between male and female
      hepcidin levels. There was significant correlation between hepcidin and ferritin
      in the control group (r=0.6, P < or = 0.0001). There was also a significant
      difference between the normal and disease groups (P < or = 0.0001). Healthy
      volunteers (n=10) showed a diurnal increase in plasma hepcidin at 4.00 pm
      compared to 8.00 am. A robust and optimised immunoassay for bioactive hepcidin
      has been produced and the patient sample results obtained further validates the
      important role of hepcidin in iron regulation, and will allow further
      investigation of this important peptide and its role in iron homeostasis.

PMID- 19839228
TI  - Measurement of total homocysteine concentrations in acidic citrate using an
      enzymatic cycling method.

PMID- 19839229
TI  - Toxicity testing: the search for an in vitro alternative to animal testing.
AB  - Prior to introduction to the clinic, pharmaceuticals must undergo rigorous
      toxicity testing to ensure their safety. Traditionally, this has been achieved
      using in vivo animal models. However, besides ethical reasons, there is a
      continual drive to reduce the number of animals used for this purpose due to
      concerns such as the lack of concordance seen between animal models and toxic
      effects in humans. Adequate testing to ensure any toxic metabolites are detected
      can be further complicated if the agent is administered in a prodrug form,
      requiring a source of cytochrome P450 enzymes for metabolism. A number of sources
      of metabolic enzymes have been utilised in in vitro models, including cell lines,
      primary human tissue and liver extracts such as S9. This review examines current
      and new in vitro models for toxicity testing, including a new model developed
      within the authors' laboratory utilising HepG2 liver spheroids within a co
      culture system to examine the effects of chemotherapeutic agents on other cell
      types.

PMID- 19839230
TI  - Meningococcal vaccination of crew members is warranted.

PMID- 19839231
TI  - A new softening agent for use on formalin-fixed, paraffin wax-embedded tissue.

PMID- 19839232
TI  - [Hypochondria in primary health care].

PMID- 19839233
TI  - [Nursing professionals joining the work force].
AB  - One's first professional experience requires an adaptation time when a sense of
      companionship and help from the institution prove important to ease this process.
      If this tutoring occurs correctly the newly certified nurse will live that
      experience in a more positive way and, therefore, joining the work force will
      provide more satisfaction for the new professional as well as for the entire
      caretaking team.

PMID- 19839234
TI  - [Sanitary education when dealing with oral anticoagulation treatment].
AB  - At present times, it is calculated there are some 800,000 people in Spain who
      need anticoagulant treatment. Oral anticoagulant treatment is used on those who
      have suffered a thromboembolic accident and to prevent the appearance of these
      episodes and their unfortunate consequences. A patient who needs anticoagulant
      treatment often comes to his/her Primary Health Care Center either for control of
      his/her anticoagulant medication or for some other chronic process which requires
      follow-up by the Primary Health Care Center team. It is essential that nursing
      professionals keep up to date about the latest anticoagulant drugs, especially
      regarding health education and prevention. This article synthesizes those items
      available in our environment about health education which should be provided to
      people undergoing anticoagulant treatment.

PMID- 19839235
TI  - [Care for ulcers having diverse etiology prospective study on PermaFoam].
AB  - PermaFoam, the dressing under study, is characterized as a polyurethane foam
      having gradient pores which, besides all the aforementioned characteristics,
      makes it possible to: rapidly absorb large quantity of seepage or exudation, cell
      remains and viscous seepage thanks to a layer of large size pores that are in
      contact with the wound; distribute and retain seepage in an intermediate layer of
      this dressing which is composed of pores having a smaller diameter; and, through
      a final layer characterized by an even smaller pore which permits a high degree
      of semi-permeability and adaptability to the distinct locales where this dressing
      needs be applied. With the objective to evaluate the usefulness of this dressing
      under study for the cicatrization of wounds having diverse etiology this research
      project was carried out. Secondary objectives included: reducing the surface of a
      wound, respecting the perilesional skin, estimating the ease of handling and
      applying this dressing, and identifying the most outstanding qualities this
      dressing provides.

PMID- 19839236
TI  - [Synthetic Nursing Index. An instrument to measure correct self-management].
AB  - Continuous improvement in quality assistance and efficiency of use of the
      sanitary resources demands professionals to consider the necessity of offering
      greater and better quality starting from the base and the tangible reality which
      we can rely upon (we have what we have, and we have to develop our activities
      based on these). To offer the greatest possible quality (we start off on the
      premise to diminish costs of non-quality: that which is done but provides no
      value to users, and what we have difficulty repeating that which was not done
      properly the first time) the Project for Participative Self-management (PAP) has
      been started, a project which indirectly will permit opting to get a variable
      economic compensation according to profits earned. And, since it is not ethical
      not licit that there be "something for everyone" (cafe para todos), nor that the
      distribution be equal for everyone, a tool has been created called the Synthetic
      Nursing Index (SNI/ISE), which enables each nursing professional to receive
      compensation based on some indicators. These indicators will evaluate if the
      quality offered and the improvement in costs of those non-quality items has
      obtained a greater or lesser consecution percentage. The SNI/ISE is a global
      clinical-care product indicator generated by "the Team", summarizing in one
      unique value a set of individual indicators, thereby facilitating its
      interpretation. Thanks to SNI/ISE, it will be possible to justify why each
      nursing professional does not receive the same variable compensation quantity
      recognizing and rewarding the work performed by each professional in an
      individual manner.

PMID- 19839237
TI  - [Handling of a Bellovac ABT drainage recuperation--blood auto transfusion
      device].
AB  - The authors describe the characteristics of the Bellovac ABT drainage
      recuperation -blood auto transfusion device along with its proper handling and
      the required nurses' care in order to minimize the risks and to provide optimum
      safety for patients. The authors also explain the potential complications and
      they discuss the main advantages and inconveniences this type of drainage has.

PMID- 19839238
TI  - [Body temperature and its importance as a vital constant].
AB  - The authors carried out a theoretical review about body temperature as a decisive
      vital sign to maintain homeostasis. Emphasis needs be placed on the importance of
      maintaining a constant temperature within a range of 36.8 degrees C +/- 0.4
      degrees C. After a brief review about thermoregulation mechanisms and thermal
      behavior in living organisms, the authors emphasize human beings' property as a
      homeo-thermal entity with characteristics which enable him to maintain a
      relatively constant body temperature in spite of physiological variations which
      make this temperature fluctuate. Upon evaluation this constant, we distinguish
      between relative values for superficial and central temperatures, detailing those
      mechanisms which influence the production or loss of heat that intervene to
      regulate body temperature by means of physioiogical responses to old and heat.
      Finally, the authors describe the necessity to maintain boy temperature following
      Virginia Henderson's fourteen necessities scale, once the factors which could
      modify it are kno wn in order to comprehend the meaning of measurements and their
      subsequent interpretation which leads to distinct Nursing diagnoses directed
      towards achieving independence in resolving this necessity.

PMID- 19839239
TI  - [Attention deficit disorder with or without hyperactivity. Relationship among
      nurses, parents and school].
AB  - Attention deficit hyperactivity disorder (ADHD) is characterized by a series of
      behaviors which interfere with the optimal evolutionary development of a child,
      at the cognitive level as well as in his/her relations with his/her family and
      integration with other children in his/her age group. An estimated 7% of children
      have this disorder. 80% of these children will continue to have problems during
      adolescence while 30 to 65% show symptoms as adults. Correct diagnosis requires,
      besides an exploration, an interview/s with teachers, family and the child and an
      evaluation of diverse tests designed for each of the implicated parties. For
      difficult cases, it is recommended there be a combined evaluation by pediatric,
      neurologist, child psychiatrist, clinical psychologist or neuropsychologist, and
      psycho-pedagogue. A multi-modal treatment has proven more effective; this
      combines pharmacological, psychological and psycho-pedagogical aspects and in
      this approach, the role of family and educators is fundamental. Primary Health
      Care Services Protocol contemplates periodical revisions, included in the Program
      to Attend to Healthy Children, which covers all children and teenagers. The role
      of nurses in these revisions is quite relevant to develop an exhaustive
      evaluation which enables collaboration in precocious detection and follow-up for
      this pathology This article hopes to facilitate this activity to all nurses
      involved in Primary Health Care, especially in pediatrics.

PMID- 19839240
TI  - [QuantiFERON. Sampling technique and handling].
AB  - The authors explain the principles and basic concepts which comprise the
      QuantiFERON technique, as well as the operating protocol to employ so that both
      the extraction and posterior handling processes of samples taken are carried out
      correctly given their importance for the effectiveness of said test. This
      technique is used to detect an infection due to the presence of Mycobacterium
      tuberculosis working with objective results complemented by other subjective
      diagnostic methods such as Mantoux, Rx evaluation or patient's clinical record.

PMID- 19839241
TI  - Something for everyone!

PMID- 19839242
TI  - The evidence for reducing inferior turbinates.
AB  - Nasal obstruction is commonly due to enlargement of the inferior turbinate. This
      review discusses the pathophysiology of turbinate enlargement, the indications
      for, and methods and outcome of turbinate reduction. All techniques are
      successful but vary in their long-term efficacy, their propensity for
      complications and the degree to which they may adversely affect nasal function.
      Newer techniques under local anaesthetic and often endoscopic control offer
      outpatient treatment with satisfactory outcomes. However selecting a particular
      technique should take account of the individual patient's features, the surgeon's
      experience and judgement and informed patient choice.

PMID- 19839243
TI  - The impact of nasal surgery on air-conditioning of the nasal airways.
AB  - Air-conditioning in the nasal passageways is one of the most important functions
      of the upper airways. By means of in-vivo-measurements and numerical simulation,
      the air-conditioning function of the nose has been extensively investigated. Less
      well known is the effect of nasal surgery on the nasal climate. The following
      study presents a summary of the effect of various rhino-surgical operations, i.e.
      turbinoplasty, septoplasty, septorhinoplasty, repair of septal perforations,
      functional and radical sinus surgery, on the air-conditioning function of the
      nose. Nasal and sinonasal interventions have been demonstrated to be associated
      with increased nasal heating and humidification when the mucosal lining is
      preserved. Radical interventions with reduction of turbinate tissue cause reduced
      nasal warming and moistening within the nasal airway, with increased risk of
      nasal dryness and crusting. Although the impact of the nasal cycle and the
      airflow distribution within the nasal cavity on nasal temperature and humidity
      distribution is not fully understood yet, too much widening of the nasal cavity
      by sinunasal interventions has carefully to be avoided.

PMID- 19839244
TI  - Expression of transient receptor potential vanilloid (TRPV) families 1, 2, 3 and
      4 in the mouse olfactory epithelium.
AB  - We investigated the expression of transient receptor potential vanilloid (TRPV)-1
      4 in the mouse olfactory epithelium (OE) in comparison to its expression in
      respiratory epithelium. CBA/J mice were used. The localization of TRPV-1, -2, -3
      and -4 in the nasal mucosa was investigated using immunohistochemistry and a
      double staining study for TRPV-1 and -2 and SP was also carried out. TRPV-1-4,
      were expressed variably in the OE with a diffuse pattern in lamina propria, and
      were expressed in respiratory epithelium with strong positive expression in
      glandular cells of lamina propria. The double-staining study revealed
      coexpression of TRPV-1 and -2 and substance P (SP) in the trigeminal nerve fibers
      of the OE. Coexpression of TRPV-1 and SP was marked around the blood vessels and
      seromucinous gland of respiratory epithelium while TRPV-2 showed no co
      localization. TRPV-1-4 were found to be localized in the mouse OE and respiratory
      epithelium. Our results suggest that TRPVs may play multiple roles in the OE,
      contributing to olfactory adaptation, olfactory/trigeminal interactions in nasal
      chemoreception and OE homeostasis; they may also be involved in olfactory
      transduction as well as olfactory dysfunction secondary to sinonasal inflammatory
      disease. TRPVs in respiratory mucosa may play a significant role in nasal
      nociception, ciliary movement and the regulation of mucous secretion.

PMID- 19839245
TI  - The Leicester semi-automated olfactory threshold test--a psychophysical olfactory
      test for the 21st century.
AB  - OBJECTIVE: Develop a useful and cost-effective olfactometer for routine clinical
      use by providing a standardised threshold test for patients with olfactory
      disorders presenting in the ENT clinic. METHOD OF STUDY: A prospective study of
      olfactory thresholds in 48 healthy volunteers on 2 consecutive occasions,
      undergoing quantitative testing with an olfactometer. Further studies of 10
      subjects performing 20 tests and 100 subjects performing a single test were
      performed. An olfactometer was designed to deliver a semi-automated threshold
      test for an odour. It contains 8 logarithmic dilutions of an odour along with a
      control valve operated by software from a laptop computer. Common potential
      variables for olfactory threshold testing were considered including peak
      inspiratory flow rate. The odours used were phenethyl alcohol (PEA) and
      eucalyptol (EUC). Subjects were asked to perform 2 tests within 1 month of each
      other and the mean threshold score for each was calculated to derive a test
      retest score. MAIN RESULTS: Consistent olfactory thresholds for PEA were achieved
      with a mean concentration of 10-4. Test-retest reliability score (r(x)) for the
      olfactometer was r(x) = 0.78 (95% CI 0.67 to 0.89). PRINCIPAL CONCLUSIONS: The
      Leicester Olfactometer provides a simple and cost-effective method of reliably
      assessing olfactory thresholds in the outpatient clinic.

PMID- 19839246
TI  - Olfactory dysfunction in Wegener's granulomatosis.
AB  - Necrotizing granulomatous inflammation of the upper respiratory tract is one of
      the hallmarks of Wegener's granulomatosis (WG), which may explain the reason for
      olfactory dysfunction in WG. However, a systematic analysis using modem olfactory
      testing tools has not been performed and potential causes of dysfunction at
      different levels of olfactory information processing remain obscure so far. In
      this study a group of 76 WG-patients was examined with sniffin'sticks screening
      12, odour threshold (T)/discrimination (D)/identification (I) TDI-score, active
      anterior rhinomanometry and a standardized questionnaire for olfactory function.
      WG-patients were aware of their olfactory dysfunction, as proven by
      psychophysiological test results. An altered olfactory function was significantly
      correlated to local administration of mupirocin and to the time interval between
      first diagnosis and study entry. None of the other variables had a statistical
      significant effect on the olfactory dysfunction.

PMID- 19839247
TI  - Epistaxis of patients admitted in the emergency department is not indicative of
      underlying arterial hypertension.
AB  - OBJECTIVE: To assess the association between epistaxis and arterial hypertension.
      METHODS: A prospective study was conducted in 80 patients admitted in the
      emergency department, 42 with epistaxis and 38 well-matched controls. Blood
      pressure was measured upon admission and by continuous 24-hour ambulatory
      monitoring on the following days. RESULTS: Estimated values upon admission did
      not differ between groups. A definitive diagnosis of hypertension was set in 18
      patients admitted for epistaxis (42.9%) and in 11 controls (28.9%, p = NS).
      Systolic pressures during the 24-hour recording period, systolic pressures during
      day and diastolic pressures during night were significantly higher among patients
      admitted for epistaxis than among controls. CONCLUSIONS: Although studies with
      larger series of patients are mandatory, epistaxis does not seem to result from
      underlying arterial hypertension.

PMID- 19839248
TI  - A study of the maxillary and sphenopalatine arteries in the pterygopalatine fossa
      and at the sphenopalatine foramen.
AB  - OBJECTIVES: Arterial ligation remains a key option in the treatment of persistent
      epistaxis and clarification of the arterial configuration of the distal
      maxillary/sphenopalatine artery is important for understanding the rationale
      behind current surgical treatments. Greater understanding of the arterial anatomy
      will reduce the risk of technical failures and improve the reliability of
      surgical interventions for persistent epistaxis and will also be useful for
      surgeries involving the pterygopalatine fossa. STUDY DESIGN: Anatomical study in
      cadavers. METHODS: This is an anatomical study of 128 cadaveric tissue blocks
      containing the pterygopalatine fossa. In total, 118 tissue blocks were
      microdissected using a Watson-Barnet dissecting microscope. Ten injected tissue
      blocks were cleared by the Spalteholz technique. Photographic records were made.
      RESULTS: Analysis demonstrated three common configurations of the maxillary
      artery in the pterygopalatine fossa: a single looped form (18%) and two double
      looped forms, 'E' (51%) and 'M' (31%). The maxillary artery bifurcates before the
      sphenopalatine foramen in 105 cases (89%). The sphenopalatine foramen lies at the
      posterior end of the middle turbinate; in 58% of cases it lies in both the
      superior and middle meati. Asymmetry in the size of the maxillary arteries was
      uncommon; only 3% could be described as 'dominant'. CONCLUSIONS: The arterial
      configuration of the maxillary artery in the pterygopalatine fossa can be complex
      but may be classified into one of three forms. Some configurations may be more
      liable to lead to difficulties with branch identification during surgical
      treatment of epistaxis particularly in combination with an inadequate osteotomy.
      Clinicians should expect to find more than one vessel exiting the sphenopalatine
      foramen and actively search for these during surgery. Asymmetry in the
      maxillary/sphenopalatine arteries is not common and contralateral ligations are
      not indicated.

PMID- 19839249
TI  - Reappraising the role of radiography in the diagnosis of chronic rhinosinusitis.
AB  - OBJECTIVE: To revaluate the role of radiography in the diagnosis of chronic
      rhinosinutis, versus the currently suggested standards of computed tomography
      (CT) or nasal endoscopy. MATERIALS AND METHODS: In total, 269 children
      consecutively admitted to our Unit for symptoms suggestive of chronic
      rhinosinusitis were included in this study; of these 222 were confirmed by
      fiberoptic nasopharyngeal endoscopy to have chronic rhinosinusitis, while 47 were
      not. Analysis of sensitivity and specificity of plain radiography by Waters'
      projection was carried. RESULTS: Radiography had a sensitivity of 84.2% (95%
      confidence interval 78.8 to 88.8), and a specificity of 76.6% (95% confidence
      interval 62.0 to 87.7) against the standard of nasal endoscopy. CONCLUSIONS: In
      routine practice, the clinical diagnosis of chronic rhinosinusitis may be
      obtained in many cases by Waters' projection radiography, limiting more expensive
      CT scanning or endoscopic techniques, which remain the reference diagnostic
      tools, to a smaller number of patients.

PMID- 19839250
TI  - Relationship between epithelial damage or basement membrane thickness and
      eosinophilic infiltration in nasal polyps with chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps is characterized by
      eosinophilic infiltration. This study hypothesized that the aggregation of the
      mucosal pathology during remodeling is related to infiltrating eosinophils in
      patients with such nasal polyps. OBJECT: To clarify the pathogenetic role of
      eosinophils in patients with CRS with nasal polyps, this study investigated the
      relationship between epithelial damage or basement membrane (BM) thickening and
      the epithelial infiltration of eosinophils in these nasal polyps. METHODS: The
      number of eosinophils that infiltrated into the epithelial and subepithelial
      layers of sinonasal tissues was counted. The staging of epithelial damage allowed
      the quantification of epithelial loss. RESULTS: Both epithelial damage and BM
      thickness in CRS, which were correlated with the number of infiltrated
      eosinophils, were significantly greater than in the control group. Neither
      parameter showed significant differences between the asthma and non-asthma
      groups. There was a significantly correlation in the eosinophilic infiltration
      between the subepithelial and epithelial layers. CONCLUSION: It is suggested that
      eosinophils that infiltrate into both the epithelial and subepithelial layers
      play a part in the process of mucosal remodeling of CRS with nasal polyps.

PMID- 19839251
TI  - Effect of corticosteroids on wound healing after endoscopic sinus surgery.
AB  - BACKGROUND: Approximately 20% patients with chronic rhinosinusitis undergoing
      Functional Endoscopic Sinus Surgery (FESS) experience impaired wound healing,
      leading to recurrences of sinusitis and polyps. METHODS: We investigated the
      efficacy of oral+ local steroids in wound healing, following FESS in subjects
      with a chronic rhinosinusitis with/without nasal polyps. Ninety-nine subjects
      were randomised to receive 6 months' treatment with mometasone furoate nasal
      spray (MFNS) 200 microg bid or placebo in double-blind manner approximately 2
      weeks after FESS. Postoperative mean total score for several endoscopic
      parameters scores assessed at 6 months was calculated as the primary efficacy end
      point. An endoscopic combination score (for inflammation, oedema, and polyps), a
      total symptoms score, and percent subjects requiring rescue medication, were
      assessed as secondary end-points. RESULTS: MFNS led to greater, although not
      significant, reductions in total endoscopic scores in all subjects, compared with
      placebo. The combination scores, however, indicated significantly improved
      healing with MFNS than with placebo for all subjects (median scores: 0.0 vs 2.0,
      p = 0.02), and particularly for subjects with nasal polyps (median scores: 2.0 vs
      4.0, p = 0.03). The total symptom scores and percent subjects requiring rescue
      medication were similar in the two groups. MFNS was well tolerated. CONCLUSIONS:
      These results suggest that treatment with MFNS following sinus surgery may
      improve wound healing, particularly in subjects with nasal polyps.

PMID- 19839252
TI  - Intracranial abscess after anterior skull base defect: does pneumocephalus play a
      role?
AB  - BACKGROUND: Intracranial complications of skull base defects are uncommon;
      however, they can be devastating when they do occur. Often these complications
      arise suddenly and without warning. Identifying patients at risk for intracranial
      abscesses may help with early diagnosis and allow for early interventions.
      OBJECTIVE: We report on 2 patients with traumatic pneumocephalus who developed
      intracranial abscesses. Our objective was to evaluate these cases and investigate
      the relationship between the presence of pneumocephalus and the formation of
      intracranial infection. METHODS: Data was reviewed on the cases of 2 patients who
      developed intracranial abscesses after pneumocephalus in the context of skull
      base defects. RESULTS: Two patients presented to our institution separately with
      the presence of intracranial abscesses. Both patients had violation of their
      anterior skull base--one from endoscopic sinus surgery, one from blunt trauma.
      Both patients had massive pneumocephalus prior to their abscess formation.
      CONCLUSIONS: Intracranial abscess formation, traumatic skull base defects, and
      massive pneumocephalus are uncommon entities, which may be associated. It may be
      prudent to have heightened suspicion for the presence of intracranial abscess
      formation in patients with massive pneumocephalus secondary to anterior skull
      base trauma.

PMID- 19839253
TI  - Bidirectional orbital approach enhances orbital abscess drainage.
AB  - OBJECTIVES: Transnasal endoscopic management of subperiosteal orbital abscess
      (SPOA) secondary to acute rhinosinusitis has become very popular over the past
      two decades. We describe our transnasal endoscopic approach for orbital
      complications secondary to acute rhinosinusitis (SPOA and orbital abscess) and
      the efficacy criteria that can be used to ensure complete drainage. METHODS: The
      charts of all patients who underwent surgery at Assaf Harofeh Medical Center
      between January 1993 and June 2007 were reviewed. Age, sex, clinical findings,
      antibiotic treatment, surgical procedure and outcome were recorded. RESULTS:
      Nineteen patients with SPOA and three with orbital abscess underwent surgery
      during which wide exposure of the periorbita was performed. If the abscess was
      not identified, bidirectional orbital manipulation, while simultaneously keeping
      a seeker in the abscess space under endoscopic view, enhanced its identification
      and successful drainage. An immediate reduction in palpable orbital pressure was
      used as an efficacy criterion for adequate drainage. CONCLUSION: The transnasal
      endoscopic approach for SPOA and orbital abscess can be enhanced by wide exposure
      of the periorbita and bidirectional orbital manipulation. Keeping track of
      orbital pressure during surgery by palpating the eye can be used as an efficacy
      criterion for assessing adequate drainage.

PMID- 19839254
TI  - The use of fibrin sealant as a glue for septoplasty and conchotomy.
AB  - OBJECTIVE: The aim of our study was to investigate glue properties of a fibrin
      sealant in cases of septoplasty and conchotomy. DESIGN: Double-blind prospective
      randomized study. MATERIALS AND METHODS: A study of 146 patients (80 M, 66 F) who
      underwent septoplasty and conchotomy was performed in Assaf Harofeh Medical
      Center Tzrifin, Israel. The patients were divided randomly into two groups: Group
      I (n = 74) underwent septoplasty with transseptal suturing, and conchotomy with
      glue as a haemostatic. Group II (n = 72) underwent septoplasty and conchotomy
      with glue as a haemostatic as well as septal cartilage and mucoperichodrial flaps
      sealant (no transseptal suturing). The glue was based on a concentrate of human
      clottable proteins and purified native human thrombin. RESULTS: Our results
      showed complete healing in both groups without significant differences. One late
      postoperative nasal bleeding occurred in group I, and none in group II.
      CONCLUSION: We conclude that the use of second-generation glue in endonasal
      surgery is well suited to stop nasal bleeding and seal intranasal flaps.
      Moreover, it might help to avoid transseptal suturing.

PMID- 19839255
TI  - Endoscopically assisted reduction of nasal bone fractures.
AB  - The standard treatment for a nasal bone fracture is closed reduction within 10
      days. After that time, callus and fibrous connective tissue will limit a precise
      reduction. This study evaluated endoscopically assisted reduction for the
      treatment of nasal bone fractures in patients who miss the optimal operating
      time. Fifteen patients underwent endoscopically assisted correction of nasal bone
      fractures. The surgery was performed with the patients under general anesthesia.
      An intercartilaginous incision was made. The depressed bony fragments were
      repositioned under endoscopic visualization. In all cases, good anatomic
      reduction was obtained, the postoperative course was uneventful, with no
      complications, and the patients were satisfied with the shape of their noses.
      Endoscopy appears to be the best tool for visualizing intraoperative
      repositioning control, enabling the surgeon to confirm a fracture site with
      callus and to perform an accurate reduction. Endoscopically assisted reduction
      provides an alternative option in the treatment of patients outside the optimal
      temporal window for surgery.

PMID- 19839256
TI  - Endoscopic sinus surgery for the odontogenic maxillary cysts.
AB  - OBJECTIVE: To evaluate the effectiveness and usefulness of transnasal endoscopic
      surgery for the treatment of odontogenic maxillary cysts. METHODS: Between
      February 2003 and February 2008, transnasal endoscopic surgery was performed
      under general anesthesia in 13 patients (male 6 and female 7, 19 to 75 years old)
      with odontogenic maxillary cysts that extended to the maxillary sinus. Ten
      patients had a radicular cyst and three patients had a dentigerous cyst. After
      the resection of anterior edge of the inferior turbinate, the lateral wall of the
      inferior nasal meatus was opened. Then, the cyst wall of the maxillary sinus was
      partially or completely removed under the endoscope. RESULTS: The cyst walls were
      completely removed in five often patients with a radicular cyst and in all three
      patients with a dentigerous cyst. Five patients with a radicular cyst received
      partial resection of the cyst wall. The affected teeth could be preserved in
      seven of ten patients with a radicular cyst and in one of three patients with a
      dentigerous cyst. There were no complications, and postoperative courses were
      uneventful. Follow-up period ranged from 11 to 72 months (mean 42 months), and no
      recurrence has been noted in any of the cases. CONCLUSIONS: Endoscopic transnasal
      surgery for the odontogenic maxillary cyst is less invasive than conventional
      dental approach, and most of the affected teeth can be preserved. This technique
      appears to be a simple and highly effective surgical treatment for the treatment
      of patients with odontogenic cysts that extend to the maxillary sinus.

PMID- 19839257
TI  - Mechanical endonasal dacryocystorhinostomy--a reproducible technique.
AB  - BACKGROUND: A study to assess the efficacy and patient acceptability of
      Mechanical Endonasal Dacryocystorhinostomy (MENDCR) in patients with acquired
      nasolacrimal duct obstruction. METHODS: A retrospective series of 38 patients
      undergoing 37 primary and 7 revision MENDCR's between March 2003 and October
      2007. Patients included had symptomatic epiphora with anatomical obstruction on
      syringing or functional obstruction on scintillography. Short-term follow up was
      assessed subjectively and objectively by anatomical patency on nasoendoscopy and
      free flow of fluorescein from eye to nose. Medium term follow up was assessed
      subjectively by telephone conversation with the patient. The average follow up
      period was 25.2 months (range 7-50). RESULTS: There were 44 DCR's performed on 38
      patients (12 male, 26female). Average patient age was 67.0years (range 16.6
      97.5). Almost all patients (95%) presented with epiphora, and a further 34% with
      dacryocystitis and/or mucocele. At short term follow up 40/44 (91%) were
      successful objectively. Of two that failed, neither had a patent ostium and one
      had recurrent mucocele. Both went on to revision surgery, which was successful at
      later review. A further two had visible ostia but no free flow of fluorescein. At
      long term follow up 90% were happy with the procedure and would undergo surgery
      again. All failures occurred by 3-month follow up. CONCLUSION: The technique of
      nMENDCR is a reproducible technique with results comparable to the original
      authors. MENDCR is an acceptable alternative to external DCR. It is well
      tolerated by patients most of whom were satisfied and would undergo the same
      procedure again.

PMID- 19839258
TI  - A rare case of oncocytic Schneiderian papilloma with intradural and intraorbital
      extension with notes of operative techniques.
AB  - Epithelial cells of cylindrical cell papilloma are oncocytes, which arise from
      the sinonasal respiratory epithelium, hence the term Oncocytic Schneiderian
      papilloma.This is a rare and benign neoplasm of the nose and paranasal sinuses
      and it should be considered in the work-up of all unilateral nasal polypoid
      lesions. Clinically behaviour is comparable to inverted papillomas for local
      recurrence and malignancy coexistence. We report a case arisen from the
      nasoethmoidal space that extended to the anterior skull base through a bone
      dehiscence with intradural invasion and orbital space involvement. Surgical
      therapy is the treatment of choice, the endonasal endoscopic approach can be used
      in most of the cases and this surgical technique is safe and suitable also in
      presence of an extra nasal extension. We describe our experience for management
      of this kind of lesions and some notes on our operative technique.

PMID- 19839259
TI  - Septal mucoperiosteal flap for the repair of unilateral choanal atresia.
AB  - The authors present a new modality of endoscopic repair for unilateral choanal
      atresia. A 14-year old girl complained of right-sided nasal obstruction.
      Endoscopy and CT scans showed unilateral bony choanal atresia. The patient
      underwent endoscopic endonasal surgery. A mucoperiosteal flap at the posterior
      part of the septum in the left, healthy nasal cavity was fashioned and the
      denuded part of the septum was removed. The atretic choanae was resected and a
      unified posterior nasal opening was formed. The flap was spread over the
      posterior septal edge and adjusted to the opposite septal side. One-year follow
      up of the patient showed no stenosis of the choanae.

PMID- 19839260
TI  - Synchronous myeloproliferative and inflammatory disease of the nasal cavity and
      paranasal sinuses: an interesting differential diagnostic problem.
AB  - The authors present a case of synchronous manifestation of a myeloproliferative-
      extramedullary plasmocytoma--and a chronic inflammatory disease of the nose and
      the paranasal sinuses. They emphasise the importance of imaging techniques and
      immunohistochemistry in the differential diagnosis. They discuss on the basis of
      published articles the new classification, clinical manifestations, diagnostic
      and therapeutical approaches of this tumour belonging to the group of monoclonal
      gammopathies, which originates from an abnormal proliferation of mature B
      lymphocytes, and is a rarity in the literature even nowadays.

PMID- 19839261
TI  - Nasal reconstruction in advanced sinunasal sarcoidosis.
AB  - INTRODUCTION: Sarcoidosis can lead to devastating nasal deformities and
      impairment of nasal respiratory function. There is only very little published
      experience with nasal reconstruction in this disease entity. In general, a
      cautious attitude prevails out of fear of complications or failure due to the
      underlying granulomatous inflammation. CASE REPORT: A 57-year-old lady presented
      to our institution with a 20-year history of sarcoidosis with sinunasal
      involvement. The findings included a saddle nose deformity, absent nasal septum
      and conchae, left-sided alar collapse and cutaneous involvement of the nasal tip
      with discoloration. In a first procedure, we performed a reconstructive nasal
      surgery with porous polyethylene grafts. In a second procedure, we used a
      paramedian forehead flap for a partial nasal reconstruction. The functional and
      asthetic improvement was very satisfactory for the patient during the 2-year
      follow-up period. CONCLUSION: This is the first reported use of a forehead flap
      in nasal sarcoidosis. It demonstrates that major reconstructive nasal surgery and
      implantation of porous polyethylene grafts can successfully be performed in
      patients with sinonasal sarcoidosis during remission.

PMID- 19839263
TI  - Methods for parasitic protozoans detection in the environmental samples.
AB  - The environmental route of transmission of many parasitic protozoa and their
      potential for producing large numbers of transmissive stages constitute
      persistent threats to public and veterinary health. Conventional and new
      immunological and molecular methods enable to assess the occurrence, prevalence,
      levels and sources of waterborne protozoa. Concentration, purification, and
      detection are the three key steps in all methods that have been approved for
      routine monitoring of waterborne cysts and oocysts. These steps have been
      optimized to such an extent that low levels of naturally occurring (oo)cysts of
      protozoan can be efficiently recovered from water. Ten years have passed since
      the United States Environmental Protection Agency (USEPA) introduced the 1622 and
      1623 methods and used them to concentrate and detect the oocysts of
      Cryptosporidium and cysts of Giardia in water samples. Nevertheless, the methods
      still need studies and improvements. Pre-PCR processing procedures have been
      developed and they are still improved to remove or reduce the effects of PCR
      inhibitors. The progress in molecular methods allows to more precise distinction
      of species or simultaneous detection of several parasites, however, they are
      still not routinely used and need standardization. Standardized methods are
      required to maximize public health surveillance.

PMID- 19839262
TI  - Signalling in malaria parasites. The MALSIG consortium.
AB  - Depending on their developmental stage in the life cycle, malaria parasites
      develop within or outside host cells, and in extremely diverse contexts such as
      the vertebrate liver and blood circulation, or the insect midgut and hemocoel.
      Cellular and molecular mechanisms enabling the parasite to sense and respond to
      the intra- and the extra-cellular environments are therefore key elements for the
      proliferation and transmission of Plasmodium, and therefore are, from a public
      health perspective, strategic targets in the fight against this deadly disease.
      The MALSIG consortium, which was initiated in February 2009, was designed with
      the primary objective to integrate research ongoing in Europe and India on i) the
      properties of Plasmodium signalling molecules, and ii) developmental processes
      occurring at various points of the parasite life cycle. On one hand, functional
      studies of individual genes and their products in Plasmodium falciparum (and in
      the technically more manageable rodent model Plasmodium berghei) are providing
      information on parasite protein kinases and phosphatases, and of the molecules
      governing cyclic nucleotide metabolism and calcium signalling. On the other hand,
      cellular and molecular studies are elucidating key steps of parasite development
      such as merozoite invasion and egress in blood and liver parasite stages, control
      of DNA replication in asexual and sexual development, membrane dynamics and
      trafficking, production of gametocytes in the vertebrate host and further
      parasite development in the mosquito. This article, which synthetically reviews
      such signalling molecules and cellular processes, aims to provide a glimpse of
      the global frame in which the activities of the MALSIG consortium will develop
      over the next three years.

PMID- 19839264
TI  - Biological and ecological characteristics of soft ticks (Ixodida: Argasidae) and
      their impact for predicting tick and associated disease distribution.
AB  - As evidence of global changes is accumulating, scientists are challenged to
      detect distribution changes of vectors, reservoirs and pathogens caused by
      anthropogenic and/or environmental changes. Statistical and mathematical
      distribution models are emerging for ixodid hard ticks whereas no prediction has
      ever been developed for argasid ones. These last organisms remain unknown and
      under-reported; they differ from hard ticks by many structural, biological and
      ecological properties, which complicate direct adaptation of hard tick models.
      However, investigations on bibliographic resources concerning these ticks suggest
      that distribution modelling based on natural niche concept and using
      environmental factors especially climate is also possible, bearing in mind the
      scale of prediction and their specificities including their nidicolous lifestyle,
      an indiscriminate host feeding and a short bloodmeal duration, as well as a
      flexible development cycle through diapause periods.

PMID- 19839265
TI  - [Acanthobothrium minus n. sp. (Tetraphyllidea: Onchobotriidae) parasite of Raja
      asterias (Elasmobranchii: Rajidae) in Mediterranean Sea].
AB  - Among tetraphyllidean cestodes, parasitic in the spiral valve of Raja asterias
      Delaroche, colected from Algerian coasts, we obtained an onchobothriid of the
      genus Acanthobothrium, differing from all species of Acanthobothrium previously
      reported from Rajidae from Mediterranea and european Atlantic coast. This Cestode
      is characterized by its very small size (1-2 mm), its number of segments of the
      strobila (4-8), the morphology and size of hooks, the limited number (17-25) of
      testes and ovarian morphology. Together, these features places this
      Acanthobothrium in group "2" as defined by Ghoshroy & Caira (2001). We describe
      this onchobothriid as Acanthobothrium minus n. sp.

PMID- 19839266
TI  - Strongyloides ratti: implication of mast cell-mediated expulsion through
      FcepsilonRI-independent mechanisms.
AB  - In order to examine whether FcepsilonRI-dependent degranulation of intestinal
      mast cells is required for expulsion of intestinal nematode Strongyloides ratti,
      CD45 exon6-deficient (CD45-/-) mice were inoculated with S. ratti. In CD45-/-
      mice, egg excretion in feces persisted for more than 30 days following S. ratti
      larvae inoculation, whereas in wild-type (CD45+/+) mice, the eggs completely
      disappeared by day 20 post-infection. The number of intestinal mucosal mast
      cells, which are known effector cells for the expulsion of S. ratti, was 75%
      lower in CD45-/- mice compared with that in CD45+/+ mice. Adoptive transfer of
      wild-type T cells from CD45+/+ mice into CD45-/- mice reduced the duration of S.
      ratti infection to comparable levels observed in CD45+/+ mice, with concomitant
      increases in intestinal mucosal mast cells. These results showed that CD45 is not
      involved in the effector function of intestinal mucosal mast cells against S.
      ratti infection. Since FcepsilonRI-dependent degranulation of mast cells is
      completely impaired in these CD45 knockout mice, we conclude that FcepsilonRI
      dependent degranulation is not required in the protective function of intestinal
      mucosal mast cells against primary infection of S. ratti.

PMID- 19839267
TI  - Study of the stress proteins secreted by Leishmania donovani after treatment with
      edelfosine, mitelfosine and ilmofosine, and morphological alterations analyzed by
      electronic microscopy.
AB  - We studied the stress proteins induced in protozoa Leishmania donovani after
      treatment with edelfosine, miltefosine and ilmofosine. We studied the
      morphological and structural modifications caused in the promastigote forms of
      the parasite after treatment with the three alkyl-lysophospholipids (ALPs). A
      resistant strain of L. donovani to miltefosine was obtained and the morphological
      modifications were observed. The stress proteins induction was studied in
      promastigote forms and also in amastigote-like forms obtained in vitro. The
      proteins synthesized with the three alkyl-lysophospholipids were compared to
      those obtained by heat shock. The axenic amastigote forms synthesized a pattern
      of different proteins for those observed in the promastigote forms. The
      morphological alterations were observed under electronic microscopy. The membrane
      and mitochondria were the organs most affected by the three ALPs. We noted an
      apparition of vacuoles and vesicles in the treated promastigotes. In the
      resistant strain, we noted myelin bodies in the treated and untreated parasites.

PMID- 19839268
TI  - Efficacy of 1% geraniol (Fulltec) as a tick repellent.
AB  - A field trial on the efficacy of 1% geraniol (Fulltec) spray against ticks has
      been carried out in two farms near Rabat (Morocco). Results clearly revealed that
      1% geraniol has a preventive effect against Hyalomma ticks. Comparison of
      geraniol sprayed cows with control herd showed a reduction of mean number of
      ticks per animal of 98.4%, 97.3% and 91.3% at respectively day 7, 14 and 21 post
      spraying. These data give evidence that the geraniol, natural product extracted
      from plants, could be an alternative to limit use of chemical acaricides, which
      efficacy is compromised by development of resistance.

PMID- 19839269
TI  - A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoproteine 63
      protects female but not male hamsters against Leishmania mexicana.
AB  - Leishmaniasis is a group of diseases caused by protozoan parasites of the
      Leishmania genus. Previous studies have shown that a DNA vaccine encoding
      Leishmania donovani antigen nucleoside hydrolase 36 and L. mexicana glycoprotein
      63 is protective in mice. We investigated here the efficacy of this DNA vaccine
      to induce protection in golden hamsters. Male hamsters were more susceptible to
      infection by Leishmania mexicana than females. Following immunization with two
      doses of the DNA vaccine, only females resulted protected while males developed
      normal lesions.

PMID- 19839270
TI  - Sandflies of the south part of Ouagadougou City, Burkina Faso.
AB  - Since 1996, the number of cases of cutaneous leishmaniasis has increased
      dramatically in Ouagadougou. Leishmania major, zymodeme MON74 was the only strain
      isolated in this focus. An epidemiological study of the phlebotomine sandflies
      fauna has been undertaken. Collections of sandflies have been carried out in six
      areas of the town during one year with two intensive collections at the end of
      the dry (May-June) and wet seasons (September-October). The only species of genus
      Phlebotomus captured was P. duboscqi. This represented 11.2% from the 4,676
      collected sandflies. P. duboscqi is a well known vector of L. major,
      nevertheless, none of the collected sandflies were infected with L. major. 16
      species of Sergentomyia were present in the south area of Ouagadougou and S.
      schwetzi was the most abundant sandfly.

PMID- 19839271
TI  - Detection of Cryptosporidium oocysts in green mussels (Perna viridis) from shell
      fish markets of Thailand.
AB  - Mussels filter large volumes of water and can concentrate pathogenic organisms,
      which may act as potential vehicles of transmission to the consumer. A survey
      study was carried out to investigate the presence of Cryptosporidium protozoan
      parasites in green mussels (Perna viridis), the smussles pecies most destined for
      consumption in Thailand. In total, 56 samples were examined from Bangkok (n = 24)
      and Samut Prakan (n = 32) a wholesale shell-fish markets located at the mouth of
      the Chao Phraya River. The market for green mussels was closed to the mussel
      culture placed along the coastal line and this localization may have significant
      economical impact if the mussels' cultures are found contaminated.
      Cryptosporidium spp. oocysts were detected by the immunofluorescence antibody
      method (IFA) in 12.5% of the samples examined. The detection of Cryptosporidium
      oocysts in green mussels' population of Samut Prakan was higher (15.6%) than in
      Bangkok market (8.3%). These differences in positive samples from the two
      locations may be caused by physical, ecological and anthropogenic conditions.
      This could relay to different contamination levels of marine water by
      Cryptosporidium oocysts and consequently to contamination of harvested shellfish
      populations. The results demonstrate that the Cryptosporidium spp. oocysts were
      found indigenous in mussels from the coastal line of Thailand, indicating that
      mussels may act as a reservoir of Cryptosporidium foodborne infections for
      humans.

PMID- 19839272
TI  - [Seroprevalence of toxoplasmosis in a rural population in south-west Gabon].

PMID- 19839273
TI  - Artemisinin-based combination therapies (ACTs) and herbal drugs crosstalk: facts
      and perspectives.

PMID- 19839275
TI  - Bioconservatism, bioliberalism, and the wisdom of reflecting on repugnance.
AB  - We consider the current debate between bioconservatives and their chief opponents
      -whom we dub bioliberals--about the moral acceptability of human enhancement and
      the policy implications of moral debates about enhancement. We argue that this
      debate has reached an impasse, largely because bioconservatives hold that we
      should honour intuitions about the special value of being human, even if we
      cannot identify reasons to ground those intuitions. We argue that although
      intuitions are often a reliable guide to belief and action, there are
      circumstances in which they are not reliable. Intuitions--including intuitions
      about enhancement--are subject to various cognitive biases rendering them
      unreliable in some circumstances. We argue that many bioconservative intuitions
      about enhancement are examples of such unreliable intuitions. Given this, it is
      unrealistic of bioconservatives to expect others to rely on their unexamined
      intuitions. Furthermore, refusing to engage in debates about the reasons and
      values that underpin their intuitions about enhancement will have the effect of
      making bioconservative voices less relevant in policy debates about enhancement
      than they would otherwise be.

PMID- 19839276
TI  - The ethics of expectations: biobanks and the promise of personalised medicine.
AB  - Expectations play a major role in 'driving' biotechnology research and
      development. However, their ethical significance has been largely overlooked.
      This article examines the dynamics and ethics of expectations surrounding
      biotechnologies, focusing on biobanks and the promise of personalised medicines.
      It explores the personal and social implications of expectations, especially
      where technologies fail to eventuate. The article identifies the claims and
      practices that support the expectations pertaining to biotechnologies and some of
      the factors that work against the fulfilment of predicted innovations. It is
      argued that the role of expectations in shaping thinking and action needs to be
      taken seriously by those who are concerned about the ethical implications of
      biotechnologies.

PMID- 19839277
TI  - Human research ethics in practice: deliberative strategies, processes and
      perceptions.
AB  - In theory, HREC members should use the ethical guidelines in the National
      Statement on the Ethical Conduct of Research Involving Humans as the basis for
      their decisions, and researchers should design their research in accordance with
      these guidelines. However, very little is known about what researchers and HREC
      members actually do in practice. In this paper, we report some of the key
      findings of the study "Human Research Ethics in Practice", a qualitative
      interview-based study of health researchers and HREC members in Victoria. The
      findings shed light on how researchers and HREC members conceptualise ethics, how
      they use the National Statement, and what deliberative strategies they employ to
      assess the ethical appropriateness of research studies. The findings also reveal
      differences and similarities between health researchers' and HREC members'
      perceptions of the roles of HRECs, and point to some sources of misunderstanding
      and tension. We examine the implications of some of these findings for the ways
      in which HRECs carry out their task, and research institutions support and
      promote ethical conduct in research amongst their staff and students. The focus
      of this study is on health research, but we suggest that the findings are highly
      relevant to all other research areas where human participants are involved.

PMID- 19839278
TI  - Charting the future from the past.

PMID- 19839279
TI  - The birth of a journal: the Canadian Journal of Public Health at the beginning of
      the XXth century.

PMID- 19839280
TI  - Thoughts from Scotland on the challenge of equitable health improvement.

PMID- 19839281
TI  - The Chief Public Health Officer's report on health inequalities: what are the
      implications for public health practitioners and researchers?
AB  - The first annual report of the Chief Public Health Officer on the State of Public
      Health in Canada draws notable attention to health inequalities in Canada. This
      report provides a compelling presentation of our current health status and the
      uneven distribution of health across the population, noting persistent and
      sizeable gaps in life expectancy, infant mortality, self-reported health,
      prevalence of chronic diseases, and other health indicators between higher- and
      lower-income groups, as well as the extraordinary disadvantage experienced by
      Canada's Aboriginal peoples. However, the report falls short of offering a
      critical approach to addressing and reducing health inequalities. It fails to
      stimulate thinking about integrated strategies by profiling current responses
      that do little to address the underlying structural drivers of health
      inequalities and ignoring the population health framework's recognition of the
      complex interactions among the determinants of health. Despite its shortcomings,
      the report shines a light on major health inequalities in Canada, providing a
      foundation for further action. Public health workers in this country must build
      on this foundation, working together and with all sectors and levels of
      government to identify and implement integrated strategies to reduce health
      inequalities and inequities in Canada.

PMID- 19839282
TI  - Public opinions on community water fluoridation.
AB  - BACKGROUND: Community water fluoridation (CWF) is currently experiencing social
      resistance in Canada. Petitions have been publicly registered, municipal
      plebiscites have occurred, and media attention is growing. There is now concern
      among policy leaders whether the practice is acceptable to Canadians. As a
      result, this study asks: What are public opinions on CWF? METHODS: Data were
      collected in April 2008 from 1,005 Canadian adults by means of a national
      telephone interview survey using random digit dialling and computer-assisted
      telephone interview technology. Descriptive and bivariate and multivariate
      logistic regression analyses were undertaken. RESULTS: Approximately 1 in 2
      Canadian adults surveyed knew about CWF. Of these, 80% understood its intended
      use, approximately 60% believed that it was both safe and effective, and 62%
      supported the idea of having fluoride added to their local drinking water. Those
      with greater incomes [OR=1.4; p<0.001] and education [OR=1.6; p<0.001] were more
      likely to know about CWF. Those with greater incomes [OR=1.3; p<0.03] and those
      who visited the dentist more frequently [OR=1.8; p<0.002] were more likely to
      support CWF, and those with children [OR=0.5; p<0.02], those who accessed dental
      care using public insurance [OR=0.2; p<0.03], and those who avoided fluoride
      [OR=0.04; p<0.001] were less likely to support CWF. CONCLUSION: It appears that
      Canadians still support CWF. In moving forward, policy leaders will need to
      attend to two distinct challenges: the influence of anti-fluoride sentiment, and
      the potential risks created by avoiding fluoride.

PMID- 19839283
TI  - Cannabis use in Canada: the need for a 'public health' approach.
AB  - Cannabis is the most commonly used illicit drug in Canada, used by 1 in 7 adults
      and 1 in 4 students. Other forms of drug use (e.g., alcohol or injection drug
      use) are increasingly approached within a public health policy framework that
      focuses on reducing harms rather than use per se. Cannabis, by contrast, remains
      formally controlled by a criminal justice approach that focuses on enforcing
      abstinence. Its use is associated with a variety of possible acute or chronic
      health problems that include cognitive and respiratory impairment, psychotic
      episodes, dependence and injury risk. The incidence of these outcomes, however,
      is predicted by early onset and a high frequency and length of use that only
      apply to a minority of users. In a public health framework, cannabis use -
      especially in young populations - should be systematically monitored and high
      risk patterns of use screened for in appropriate settings, e.g., schools and GP
      offices. Evidence-based primary and secondary prevention, treatment and
      enforcement need to be targeted at these high-risk patterns of use. Given the
      large cannabis user population, especially among young people, and the failure of
      the criminalization approach to discourage use, a public health framework for
      cannabis use is urgently needed in Canada.

PMID- 19839284
TI  - How many people in Canada use prescription opioids non-medically in general and
      street drug using populations?
AB  - OBJECTIVE: Medical prescriptions for opioids as well as their non-medical use
      have increased in Canada in recent years. This study aimed to estimate the number
      of non-medical prescription opioid (PO) users in the general and street drug
      using populations in Canada. METHODS: The number of non-medical PO users among
      the general population and the number of non-medical PO users, heroin users, or
      both among the street drug using population was estimated for Canada and for the
      most populous Canadian provinces. Different estimation methods were used: 1) the
      number of non-medical PO users in the Canadian general population was estimated
      based on Canadian availability data, and the ratio of US availability to non
      medical PO use from US survey data; 2) numbers within the street drug using
      population were indirectly estimated based on overdose death data, and a key
      informants survey. Distribution and trends by usage of opioids were determined by
      using the multi-site Canadian OPICAN cohort data. RESULTS: Between 321,000 to
      914,000 non-medical PO users were estimated to exist among the general population
      in Canada in 2003. The estimated number of non-medical PO users, heroin users, or
      both among the street drug using population was about 72,000, with more
      individuals using nonmedical PO than heroin in 2003. Based on data from the
      OPICAN survey, in 2005 the majority of the street drug using population in main
      Canadian cities was non-medical PO users, with the exception of Vancouver and
      Montreal. A relative increase of 24% was observed from 2002 to 2005 in the
      proportion of the street drug using population who used non-medical POs only.
      DISCUSSION: There is an urgent need to further assess the extent and patterns of
      non-medical prescription opioid use, related problems and drug distribution
      channels in Canada.

PMID- 19839285
TI  - Vendor compliance with Ontario's tobacco point of sale legislation.
AB  - OBJECTIVE: On May 31, 2006, Ontario joined a small group of international
      jurisdictions to implement legislative restrictions on tobacco point of sale
      promotions. This study compares the presence of point of sale promotions in the
      retail tobacco environment from three surveys: one prior to and two following
      implementation of the legislation. METHOD: Approximately 1,575 tobacco vendors
      were randomly selected for each survey. Each regionally-stratified sample
      included equal numbers of tobacco vendors categorized into four trade classes:
      chain convenience, independent convenience and discount, gas stations, and
      grocery. Data regarding the six restricted point of sale promotions were
      collected using standardized protocols and inspection forms. Weighted estimates
      and 95% confidence intervals were produced at the provincial, regional and vendor
      trade class level using the bootstrap method for estimating variance. RESULTS: At
      baseline, the proportion of tobacco vendors who did not engage in each of the six
      restricted point of sale promotions ranged from 41% to 88%. Within four months
      following implementation of the legislation, compliance with each of the six
      restricted point of sale promotions exceeded 95%. Similar levels of compliance
      were observed one year later. Grocery stores had the fewest point of sale
      promotions displayed at baseline. Compliance rates did not differ across vendor
      trade classes at either follow-up survey. Point of sale promotions did not differ
      across regions in any of the three surveys. CONCLUSION: Within a short period of
      time, a high level of compliance with six restricted point of sale promotions was
      achieved.

PMID- 19839286
TI  - [Ethical considerations of a public health intervention aimed at reducing the
      risk of HIV transmission in HIV-seropositive-populations who are unwilling to
      take precautions].
AB  - OBJECTIVES: 1) To describe a public health intervention aimed at reducing the
      risk of HIV transmission by seropositive people who are unwilling or unable to
      take precautions to counter HIV transmission; 2) To document ethical principles
      that help front-line health care professionals arrive at justifiable decisions
      and actions. PARTICIPANTS: Front-line health care professionals dealing with
      these cases. LOCATION: Intervention developed by la Direction de la sante
      publique de l'Agence de la sante et des services sociaux de Montreal.
      INTERVENTION: A comite d'aide aux intervenants (CAI) was struck to advise health
      care professionals. To document the ethical principles that help front-line
      health care professionals in these situations, we undertook a multiple case study
      based on the committee's approach to counselling care providers for each of the
      26 cases dealt with by the CAI between November 1996 and January 2003. RESULTS:
      We identified 7 ethical pitfalls: expecting immediate ideal results;
      simplification of complex situations; generalizing uncritically from a particular
      case; uncritical ethical bias against coercive measures; inability or refusal to
      recognize and accept limits; failure to anticipate unintended consequences of an
      action; acting on incomplete, unvalidated, or unverifiable information.
      CONCLUSION: A process of mutually exercised critical reflection can help health
      care professionals to identify and avoid ethical pitfalls and arrive at
      justifiable decisions and actions.

PMID- 19839287
TI  - The feasibility of using an 'opt-out' approach to achieve universal HIV testing
      of tuberculosis patients in Alberta.
AB  - OBJECTIVE: Universal HIV testing of tuberculosis (TB) patients, defined as
      testing greater than 80% of incident cases, has been recommended but not achieved
      in Canada. The objectives of this study were: i) to assess the success of an 'opt
      out' approach, whereby HIV testing is routine unless the patient specifically
      chooses otherwise, and ii) to determine the risk factors for HIV in patients
      tested before and after this approach was implemented. METHODS: TB and HIV
      databases in the province of Alberta were cross-matched before HAART (highly
      active anti-retroviral therapy) was available (1991-1997), after HAART but before
      'opt-out' testing was implemented (1998-2002), and after 'opt-out' testing was
      implemented (2003-2006), and the HIV status of TB patients in each time period
      was described. The demographic and clinical characteristics of HIV-positive and 
      negative TB patients aged 15-64 years were compared. RESULTS: HIV testing of TB
      patients increased from 11.5% before HAART, to 44.9% after HAART but before 'opt
      out' testing, to 81.9% after 'opt-out' testing was implemented. Between 1991 and
      2006, 50 TB patients were diagnosed with HIV co-infection, all in the age group
      15-64 years. Among TB patients aged 15-64 years who were HIV tested, those
      testing positive were significantly less likely to be female and to have
      respiratory TB and significantly more likely to have both respiratory and non
      respiratory TB. The prevalence of HIV positivity in HIV-tested TB patients aged
      15-64 years was 7.4% in 2003-2006. CONCLUSION: Universal HIV testing of TB
      patients is achievable through 'opt-out' HIV testing.

PMID- 19839288
TI  - Hepatitis C and HIV prevalence using oral mucosal transudate, and reported drug
      use and sexual behaviours of youth in custody in British Columbia.
AB  - BACKGROUND: Youth in custody have high-risk drug use and sexual behaviours. HIV
      prevalence in this population was assessed in British Columbia (BC) in 1994 but
      hepatitis C virus (HCV) prevalence has never been measured. We sought to
      determine: 1) the performance of the OraSure, a non-invasive device for oral
      mucosal transudate (OMT) specimen collection, to detect HCV and HIV antibodies;
      2) the prevalence of HCV and HIV among youth in custody; and 3) the factors
      associated with intravenous drug use and sex for trade. METHODS: OraSure was
      validated in 110 adults with known HIV and HCV sero-status. Nurses administered
      an anonymous survey and collected OMT samples from youth aged 14-19 years in BC
      youth custody centres. RESULTS: Antibody detection in OMT had 96.4% sensitivity
      for HIV and 94.6% for HCV. 417 youth were enrolled; 22% were female; 48% reported
      Aboriginal ethnicity. Although 98.3% reported ever using drugs, <8% reported
      injection drug use (IDU). IDU was independently associated with age of first
      sexual intercourse (inverse association) and sex for trade (sex in exchange for
      money, drugs, food or shelter) (OR 4.28; 95% CI: 1.56-11.75). Females were >9
      times more likely to report sex for trade. Five Aboriginal youth were identified
      with HCV; prevalence estimate 1.2% (95% CI: 0.53-2.77%); 3 reported injecting
      drugs, the other 2 reported using cocaine/crack and sharing non-injection drug
      paraphernalia. Two youth were identified with HIV, prevalence estimate 0.48% (95%
      CI: 0.14%-1.72%). CONCLUSION: IDU, HCV and HIV prevalence remain low.
      Interventions are needed to prevent transition to IDU and further opportunities
      for prevention and harm reduction should be explored while the youth are in
      custody.

PMID- 19839289
TI  - Ontario's daily physical activity policy for elementary schools: is everything in
      place for success?
AB  - OBJECTIVES: The development, implementation, and evaluation of policies may play
      an important role in promoting health behaviours such as physical activity. The
      Ontario Ministry of Education (OME) recently mandated Memorandum No. 138
      requiring daily physical activity (DPA) for Ontario elementary students in grades
      one through eight. The purpose of this paper is to examine implementation
      strategies. METHODS: Hogwood and Gunn's 10 preconditions for "perfect
      implementation" are used to examine publicly available Ministry DPA policy
      documents to assess whether these implementation strategies have been considered
      in the policy documents. RESULTS: Several preconditions (e.g., allocation of
      resources, task specification) appear to have been considered, however a number
      of preconditions (e.g., the sustainability of resources, extent to which the
      policy is valued, and evaluation plans) thought to be important require
      additional attention to ensure optimal DPA implementation. CONCLUSIONS:
      Additional reflection upon Hogwood and Gunn's implementation preconditions would,
      in our opinion, assist in facilitating optimal DPA implementation as per
      Memorandum No. 138.

PMID- 19839290
TI  - Neighbourhood contexts and low birthweight: social disconnection heightens single
      parents risks in Saskatoon.
AB  - BACKGROUND: The majority of research to date on low birthweight (LBW) has
      emphasized maternal characteristics, and less so how maternal risk is shaped (via
      contextual factors). This study aims to understand how neighbourhood
      characteristics influence LBW, independently and in interaction with individual
      factors, in the context of community-defined neighbourhoods. METHOD: All
      singleton births for a 3-year period (1992-1995; n=8504) to mothers resident in
      Saskatoon comprised the study population. Data included were child and
      mother's/father's characteristics and six neighbourhood characteristics: socio
      economic disadvantage, social disconnection, physical condition, population
      density, availability and accessibility of local programs and services, and
      smoking prevalence. Multilevel modeling for a binary outcome (LBW) was employed;
      odds ratios and 95% confidence intervals for the final model were reported.
      RESULTS: Newborns in families receiving income assistance, with a mother over 40,
      and whose mother had previous stillbirths were at greater risk for LBW; however,
      mothers who had more than one previous live birth were less likely to have a LBW
      baby. Independent of individual-level risk factors, infants in socio-economically
      disadvantaged neighbourhoods were at increased risk for LBW (OR 1.34; 95% CI
      1.07, 1.68). Most interestingly, the risk of LBW among infants born to single
      mothers was exacerbated by greater level of neighbourhood social disconnection.
      Neighbourhoods with low levels of social disconnection have a lower risk of LBW
      among single mothers (OR=0.89, 95% CI 0.72, 1.17) compared to those with high
      levels (OR=1.57, 95% CI 1.18, 1.93). CONCLUSION: Neighbourhood contextual factors
      influence the risk of LBW directly, via independent effects, as well as through
      moderating the risk of individual factors. Studies that simultaneously examine
      both individual and contextual effects on LBW could provide a stronger
      evidentiary base for multiple points of interventions targeting individuals as
      well as settings.

PMID- 19839291
TI  - Food insecurity and participation in community food programs among low-income
      Toronto families.
AB  - OBJECTIVES: Responses to food insecurity in Canada have been dominated by
      community-based food initiatives, while little attention has been paid to
      potential policy directions to alleviate this problem. The purpose of this paper
      is to examine food security circumstances, participation in community food
      programs, and strategies employed in response to food shortages among a sample of
      low-income families residing in high-poverty Toronto neighbourhoods. METHODS:
      Data from surveys conducted with 484 families and neighbourhood mapping were
      analyzed. RESULTS: Two thirds of families were food insecure over the past 12
      months and over one quarter were severely food insecure, indicative of food
      deprivation. Only one in five families used food banks in the past 12 months and
      the odds of use were higher among food-insecure families. One third of families
      participated in children's food programs but participation was not associated
      with household food security. One in 20 families used a community kitchen, and
      participation in community gardens was even lower. It was relatively common for
      families to delay payments of bills or rent and terminate services as a way to
      free up money for food and these behaviours were positively associated with food
      insecurity. DISCUSSION: While documenting high rates of food insecurity, this
      research challenges the presumption that current community-based food initiatives
      are reaching those in need. Public health practitioners have a responsibility to
      critically examine the programs that they deliver to assess their relevance to
      food-insecure households and to advocate for policy reforms to ensure that low
      income households have adequate resources for food.

PMID- 19839292
TI  - Adoption of the Healthy Heart Kit by Alberta family physicians.
AB  - OBJECTIVE: The Healthy Heart Kit (HHK) is a risk management and patient education
      kit for the prevention of cardiovascular disease (CVD) and the promotion of CV
      health. There are currently no published data examining predictors of HHK use by
      physicians. The main objective of this study was to examine the association
      between physicians' characteristics (socio-demographic, cognitive, and
      behavioural) and the use of the HHK. METHODS: All registered family physicians in
      Alberta (n=3068) were invited to participate in the "Healthy Heart Kit" Study.
      Consenting physicians (n=153) received the Kit and were requested to use it for
      two months. At the end of this period, a questionnaire collected data on the
      frequency of Kit use by physicians, as well as socio-demographic, cognitive, and
      behavioural variables pertaining to the physicians. RESULTS: The questionnaire
      was returned by 115 physicians (follow-up rate = 75%). On a scale ranging from 0
      to 100, the mean score of Kit use was 61 [SD=26]. A multiple linear regression
      showed that "agreement with the Kit" and the degree of "confidence in using the
      Kit" was strongly associated with Kit use, explaining 46% of the variability for
      Kit use. Time since graduation was inversely associated with Kit use, and a trend
      was observed for smaller practices to be associated with lower use. CONCLUSION:
      Given these findings, future research and practice should explore innovative
      strategies to gain initial agreement among physicians to employ such clinical
      tools. Participation of older physicians and solo-practitioners in this process
      should be emphasized.

PMID- 19839293
TI  - Integrating psychologists into the Canadian health care system: the example of
      Australia.
AB  - Canada and Australia share many similarities in terms of demographics and the
      structure of their health systems; however, there has been a divergence in policy
      approaches to public funding of psychological care. Recent policy reforms in
      Australia have substantially increased community access to psychologists for
      evidence-based treatment for high prevalence disorders. In Canada, access remains
      limited with the vast majority of consultations occurring in the private sector,
      which is beyond the reach of many individuals due to cost considerations. With
      the recent launch of the Mental Health Commission of Canada, it is timely to
      reflect on the context of the current Canadian and Australian systems of
      psychological care. We argue that integrating psychologists into the publicly
      funded primary care system in Canada would be feasible, beneficial for consumers,
      and cost-effective.

PMID- 19839294
TI  - [The relationship between social support, psychological stress and the risk of
      developing anxiety disorders in men and women: results of a national study].
AB  - OBJECTIVE: Investigate the links between different types of social support,
      psychological well-being and distress among individuals with anxiety disorders.
      METHODS: Data were drawn from the Canadian Community Health Survey (CCHS cycle
      1.2) which had 36,984 participants, 1,803 of whom presented with anxiety
      disorders. Classical linear regression analyses were conducted to examine the
      links between different social support dimensions and psychological well-being on
      one hand, and psychological distress on the other hand. RESULTS: Women reported
      perceiving significantly higher levels of affective, emotional/informational,
      tangible support and positive social interactions than men. After controlling for
      potentially confounding variables (socio-demographic variables and the presence
      of a major depressive disorder), three types of social supports appeared to be
      predictors for the psychological well-being of women with anxiety disorders:
      positive social interactions, emotional/informational support, and affective
      support. For men, none of the social support variables were significantly
      associated with psychological well-being or distress. The comparisons of Beta
      coefficients do not show any significant difference between the sexes.
      CONCLUSION: Social support appears to be a positive predictor for psychological
      well-being among women with an anxiety disorder. No associations were found
      between social support variables and the psychological distress perceived by men
      and women. The results of this study therefore confirm the importance of teaching
      appropriate support strategies adapted for anxiety disorders. Future studies
      should assess negative social interactions in addition to social support.

PMID- 19839295
TI  - [The validation of a new population surveillance system that analyzes the daily
      mortality rates in Montreal].
AB  - OBJECTIVES: Since 2004, a surveillance system provides counts, almost in real
      time, of the number of deaths per day occurring on the Island of Montreal. The
      validity of this monitoring tool and its ability to detect spikes in daily
      deaths, such as can occur due to heat waves, have been evaluated. METHOD:
      Comparison of the number of deaths per day recorded in the monitoring system with
      the number of deaths per day recorded in the official record of deaths in Quebec
      for 134 days of 2004. RESULTS: The monitoring system is accurate (for over 73% of
      days, the difference in the number of deaths between the two files falls within a
      range of +/-3 deaths given an average of 43 deaths per day). The system
      identifies more than 80% of all deaths and is efficient in identifying days with
      excess deaths that are 20% above the average. DISCUSSION: This novel monitoring
      system, based on data used mainly for management of medical services, meets
      contemporary public health requirements in terms of early detection of unusual
      health events.

PMID- 19839296
TI  - Workplace and workforce health information systems in healthcare: acknowledging
      the role of university researchers and highlighting the importance of health and
      safety committee capacity-building.

PMID- 19839297
TI  - [Gas pipeline leak detection based on tunable diode laser absorption
      spectroscopy].
AB  - The principle of tunable diode laser absorption spectroscopy and harmonic
      detection technique was introduced. An experimental device was developed by point
      sampling through small multi-reflection gas cell. A specific line near 1 653. 7
      nm was targeted for methane measurement using a distributed feedback diode laser
      as tunable light source. The linearity between the intensity of second harmonic
      signal and the concentration of methane was determined. The background content of
      methane in air was measured. The results show that gas sensors using tunable
      diode lasers provide a high sensitivity and high selectivity method for city gas
      pipeline leak detection.

PMID- 19839298
TI  - [Characterizations of InP in terahertz region].
AB  - Terahertz time-domain spectroscopy (THz-TDS), which directly measures the THz
      wave's temporal electric field, can give the amplitude and phase of the THz wave
      pulse simultaneously. THz-TDS is attracting more attention among scientists. InP
      with short carrier average collision time and low effective mass is growing up as
      one of the best photoconductive materials for emitting and detecting THz waves.
      An n-type InP of 0.35 omega x cm was characterized over the range from 0.2 to 4
      THz at room temperature in the present paper with THz time-domain spectroscopy,
      which was placed in a closed box purged with dry nitrogen gas. Some THz optical
      properties, such as complex refractive index, dielectric constant, and
      conductivity, were extracted, based on more exact iterative method with new
      initial function. Drude model was also applied for simulation, which fitted well
      with the experimental results. Finally, the carrier average collision time,
      density and mobility of the InP were also characterized.

PMID- 19839299
TI  - [Impact of laser energy on measurement of fly ash carbon content].
AB  - A laser induced breakdown spectroscopy-based apparatus for the analysis of
      element, employing a 532 nm laser and a multi-channel optical spectrometer with a
      non-intensified CCD array, has been built and tested. It was applied to analyze
      the carbon content of coal fly ash. Seven groups of pulse laser in the range of
      35 to 98 mJ were used to ablate the fly ash samples. The electron densities and
      plasma temperatures with different laser energy were determined, and the
      influence of laser energy on the intensity of analysis carbon lines was also
      analyzed. The results show that carbon line intensity increases slowly with the
      increase in laser energy in the range of 35 to 46 mJ, and increases fast in the
      range of 46 to 78 mJ, then trends to saturation and has a little drop. At the
      same time, air breakdown has increased significantly, and has an obvious effect
      on sample plasma. Furthermore, the electron density and plasma temperature
      increase with the laser energy until 78 mJ and then begin to decrease. It
      indicates that a proper laser energy can enhance the plasma emission signal, and
      avoid the negative impact of air breakdown that prevent the pulse laser from
      reaching the surface of sample and ablating it. In this experiment situation, the
      measurement accuracy of the carbon line can be improved.

PMID- 19839300
TI  - [Tunable fiber laser based photoacoustic spectroscopy for acetylene detection].
AB  - An acetylene detection system has been constructed with a tunable erbium-doped
      fiber laser (TEDFL) based photoacoustic spectrometer. Combining wavelength
      modulation and second harmonic signal detection technique, the system is able to
      effectively eliminate the background noise generated by absorption of the cell
      windows and the wall of the acoustic resonator. The system was applied to low
      concentration acetylene flowing measurement, through optimizing the systemic
      optics, acoustics and electron detection technique condition. The experimental
      results show that the second harmonic amplitude is directly proportional to gas
      concentration. Their linear pertinence coefficient is 0.999 53. The system
      sensitivity limit for acetylene detection is 0.3 ppm under atmosphere pressure
      with 100 ms time constant and 3. 5 mW average optical power. The TEDFL was used
      as light source in stead of the DFB diode laser which is relatively costly. The
      system appears promising as a basis for developing cheap, practical, portable
      spectroscopy instruments for trace gas detection. The detection sensitivity could
      be greatly improved by using multi-path cell or increasing the laser power with
      EDFA.

PMID- 19839302
TI  - [Collisional energy transfer between excited Rb atoms].
AB  - Energy pooling (EP) was observed in Rb vapor following pulsed optical excitation
      to the 5P1/2 state. The 5P3/2 state was populated by the energy transfer process:
      Rb(5P1/2)+Rb(5S1/2) --> Rb(5P3/2)+Rb(5Sl/2). The resulting densities of Rb atoms
      at the 5P1/2 level were obtained from the absorption of narrow spectral line from
      a Rb hollow cathode lamp, connecting the 5P1/2 state to 7S state. Since the
      effective lifetimes of the 5P1/2 and 5P3/2 states are approximately equal, the
      densities of the 5P3/2 level were obtained from the D2 to D1 fluorescence ratios
      where D1 and D2 are lines of the 5P1/2 --> 5S1/2 and 5P3/2 --> 5S1/2 transition.
      Because the time of the fine structure exchanging is much shorter than the
      lifetime of the 5D state, the fluorescence originating from the 5D state produced
      by the 5P1/2 + 5P3/2 and 5P3/2 + 5P3/2 processes follows the instantaneous
      production rate of the 5P1/2 + 5P1/2 process. It is clear that 5P/2 + 5P3/2 and
      5P3/2 + 5P3/2 collisions can significantly influence the results obtained for the
      5P1/2 + 5P1/2 rate since the energy defect for 5D state is much smaller for 5P1/2
      + 5P3/2 and 5P3/2 + 5P3/2 collisions than for 5P1/2 + 5P1/2 collisions. Effective
      lifetimes of the 5P levels were calculated using radiation trapping theory. The
      time-integrated populations and signals were studied and analyzed. The resulting
      fluorescence included the direct component emitted in the decay of the optically
      excited 5P1/2 state and the sensitized component arising from the collisions for
      populating 5D state at different cell temperature. These relative intensities
      were combined with the measured excited atom densities to yield absolute energy
      pooling rate coefficients. The cross sections (in units of 10(-14) cm2) for the
      energy-pooling collisions [i. e. , 5P1/2 + 5P1/2, 5P1/2 + 5P3/2, 5P3/2 + 5P3/2]
      are 0.78, 2.9 and 3.1, respectively. The dependence of the rates upon energy
      defect deltaE was examined, but the 5D3/2 level was approximately equally
      populated in 5P3/2 + 5P3/2 (deltaE = 68 cm(-1)) and 5P3/2 + 5P1/2 (deltaE = 306
      cm(-1)) collisions. The 5P1/2 + 5P3/2 collisions are as efficient as 5P3/2 +
      5P3/2 for populating 5D3/2 state.

PMID- 19839301
TI  - [Absorption spectrum study of HeLa cells treated with vacuum and low-energy ions
      implantation].
AB  - Mineral oil was selected to protect HeLa cells from water evaporation during low
      energy ions implantation in the present paper. Then, HeLa cells having been
      treated with vacuum and low-energy N+ ions implantation were used to collect
      ultraviolet absorption spectrum by spectrophotometer. Analytical results
      indicated that HeLa cells had some characteristic absorption peaks near 202 and
      260 nm, respectively. And then the study also found: (1) The spectral intensity
      increased with the vacuum treatment time. In addition, the effect of vacuum on
      cellular spectrum was greater than that of mineral oil. (2) The influence of low
      energy N+ ions on absorption spectrum was far more than that of vacuum. (3) The
      spectral intensity increased with the implantation dose. According to these
      results, the effect of low-energy N+ ions implantation and vacuum on tumorous
      cells (HeLa cells), especially on the molecular configuration and component of
      tumorous cells (HeLa cells) was discussed. In a word, this study provides a basis
      for further research on the functionary mechanism of low-energy ions implantation
      on biomaterial.

PMID- 19839303
TI  - [Reactive and nonreactive energy transfer in Cs(6D(J))+ (H2, He) collisions].
AB  - Cs vapor, mixed with a gas was irradiated in a glass fluorescence cell with
      pulses of 886nm radiation from a YAG-laser-pumped OPO laser, populating 6D3/2
      state by two-photon absorption. Cross sections for 6D3/2 --> 6D5/2 transition
      induced by collisions with various H(e) atoms and H2 molecules were determined
      using methods of atomic fluorescence. The resulting fluorescence included a
      direct component emitted in the decay of the optically excited state and a
      sensitized component arising from the collisionally populated state. At the
      different densities, we have measured the relative time-integrated intensities of
      the components and fitted a three-state rate equation model to obtain the cross
      sections for 6D3/2 --> 6D5/2 transfer: sigma = (55 +/- 13) x 10(-16) and (16 +/-
      4) x 10(-16) cm2 for H2 and H(e), respectively. The cross sections for the
      effective quenching of the 6D5/2 state were also determined. The total transfer
      rate coefficients from the 6D5/2 state for H(e) is small [1.2 x 10(-10) cm3 x s(
      1)]. The total quenching rate coefficient of the 6D5/2 state is larger for H2
      [6.7 x 10(-10) cm3 z s(-1)]. For H2 case, the quenching rate coefficient
      corresponds to reaction and nonreactive energy transfer. Evidence suggests that
      the nonreactive energy transfer rate coefficient is [6.3 x 10(-10) cm3 x s(-1)].
      Hence the authors estimated the cross section (2.0 +/- 0.8) x 10(-16) cm2 for
      reactive process Cs(6D5/2) + H2 --> CsH + H. Using the dependence on the pressure
      of H2 (or H(e)) of the integrated fluorescence monitored at the 6D5/2 --> 6P3/2
      transition the cross section (4.0 +/- 1.6) x 10(-16) cm2 for Cs (6D3/2) + H2 -->
      CsH + H was obtained. Thus, the relative reactivity with H2 follows an order of
      Cs (6D3/2) > Cs (6D5/2).

PMID- 19839304
TI  - [Influence of fluorescent dye ultrathin layer on luminescence spectra in organic
      light-emitting diodes].
AB  - By using an ultrathin dopant dye layer deposited on the top of host materials,
      the influence of concentration of three fluorescent dyes, dimethylquinacridone
      (DMQA), 4-(dicyanomethylene)-2-t-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H
      pyran (DCJTB), and 5,6,11,12-tetraphenylnaphthacene (rubrene), on the
      luminescence spectra of OLEDs was studied. The characteristic of the brightness
      efficiency-bias voltage performance was investigated. The results showed that
      compared to the conventional doping devices, the devices consisting of ultrathin
      dye layer exhibited a weak peak originating from host matrix, and the more
      obvious concentration quenching was existent. The degree of concentration
      quenching for the three ultrathin doping dyes from high to low is in the order of
      DMQA, DCJTB and rubrene. Meanwhile, the authors used the photoluminescence
      spectra of these three dopants dilute solution to testify the relationship
      between EL properties of OLEDs and concentration quenching of these dyes.

PMID- 19839305
TI  - [Luminescence dynamics analysis on ruthenium polypyridyl complexes bonding to
      DNA].
AB  - Time-resolved spectra of six kinds of ruthenium polypyridyl complexes [Ru(L)2
      (R)]2+ (L = bpy, phen, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, R = 7
      CH3-dppz, 7-F-dppz, dpbpd(NH2)2) bonding to calf thymus DNA in aqueous solution
      were compared and analyzed by using the three energy level kinetic model. And the
      effects of the substituent groups on the interaction ways for the ruthenium
      complexes bonding to DNA were discussed. The result shows that first, the six
      complexes all show two binding modes on bonding to DNA, i.e. the side-on binding
      mode and the perpendicular binding mode, and the later one is considered as a
      main binding way. Second, the properties of substituent groups have an important
      impact on the relative weight of the two binding modes. The conclusion offers a
      dynamics argument to study the interaction mechanism for the complex bonding to
      DNA further.

PMID- 19839306
TI  - [Detecting the information of cucumber in greenhouse for picking based on NIR
      image].
AB  - For the cucumber harvesting robot, the identification of target information is
      one of important tasks in the automation of fruit-picking. In order to implement
      spatial fruit localization and quality discrimination in greenhouse, this paper
      presented a machine vision algorithm for the recognition and detection of
      cucumber fruits based on near-infrared spectral imaging. By comparing the
      spectral reflectance of cucumber plant (fruit, leaf and stem) from visible to
      infrared region (325-1 075 nm) measured by ASD FieldSpec Pro VNIR spectrometer, a
      monospectral near-infrared image at the 850 nm sensitive wavelength was captured
      to cope with the similar-color segmentation problem in complex environment. Then,
      a method of fruit extraction was developed on the basis of the following steps.
      Firstly, from the gray level histogram it was observed that the pixels of fruit
      distributed on the right are lesser than that of background, so "P parameter
      threshold method" was used to image segmentation. Subsequently, divided local
      image was partitioned into several sub-blocks by the application of adaptive
      template mining, which was feasible for processing the fruit with long-column
      feature. Finally, noises including parts of stem and leaf were eliminated using
      estimation condition of barycentre position and area size, proved by relative
      experiment In addition, the region for robotic grasping was established by gray
      variation between fruit-handle and fruit pedicel, as the quality feature was
      extracted with morphological characteristics of the centre-line length and the
      fruit flexure degree. A detecting experiment was carried out on 30 images with
      cucumber fruits and 10 images with no fruits, which were taken in a changing
      greenhouse environment. The results indicate that the accuracy rate of the
      recognition was 83.3% and 100%, while the success rate of effectively acquiring
      the grasping region was 83.3%, which can meet the demand of robotic fruit
      harvesting.

PMID- 19839307
TI  - [Study on denoising near infrared spectra of wood based on wavelet transform].
AB  - Near infrared (NIR) spectra of wood samples are often confused by a series of
      noise, which greatly influences accurate analytical result. In order to improve
      analytical precision, the authors need to pretreat the spectrum data. Derivative
      can correct baseline and background effects, increasing the resolution ratio of
      the spectra. However, it also increases the noise at the same time. The present
      paper aims at using wavelet transform to eliminate the noise of the near infrared
      first derivative spectrum of wood with the methods of 9 point smoothing spectrum,
      25 point smoothing spectrum, the nonlinear wavelet hard-threshold spectrum, the
      nonlinear wavelet soft-threshold spectrum, 9 point smoothing+wavelet transform
      and 25 point smoothing spectrum+ wavelet transform. The results show that the
      wavelet transform has particular advantage on noise elimination of the near
      infrared spectra while reserving the useful information of spectrum. It can also
      improve the signal to noise ratio of spectrum, promising the prospect of a wide
      application in the wood near infrared spectroscopic analysis.

PMID- 19839308
TI  - [Egg quality prediction by using Fourier transform near infrared reflectance
      spectroscopy (FT-NIR)].
AB  - The objective of the present study is to investigate the feasibility of using FT
      NIR to determine egg quality: egg albumen height (EAH); Haugh unit (HU); air cell
      height (ACH); air cell diameter (ACD); egg shape index (ESI) and egg weight (EW).
      All eggs were stored in the same environment with 16 degrees C and 75% relative
      humidity after collection. Calibrations were developed using a leave-one-out
      cross validation procedure under partial least-squares regression. The different
      optimal parameter comparisons showed that Savitzky-Golay filter method and second
      derivatives can give the best calibration for all the measured values. The
      partial least-square analysis showed that R2 of the EAH, ACD and ACH are 0.867,
      0.821 and 0.865, respectively. The RMSECV values are 0.476, 0.014 and 0.479 for
      EAH, ACD and ACH, respectively. The correlation coefficients of external
      validation for 33 eggs are 0.873, 0.861 and 0.895 for EAH, ACD and ACH,
      respectively. The external-validation results are not significant different from
      actual measurements (P > 0.05) for EAH, ACD and ACH. All models cannot give the
      reasonable results for EW, ESI and HU. As the HU cannot be measured correctly by
      using FT-NIR and also is highly correlated with EAH, the authors suggested the
      possibility to revise the currently used measurement standard. Our results showed
      that FT-NIR could be used to test the egg albumen height, air cell height and air
      cell diameter.

PMID- 19839309
TI  - [FTIR and XRD analysis studies of intercalation of kaolinite with benzamide].
AB  - Benzamide was intercalated into kaolinite by replacing DMSO pre-intercalated.
      Pure kaolinite-benzamide intercalation compounds were obtained by washing
      resulting products with acetone. The analysis of XRD shows that the basal spacing
      of kaolinite-benzamide intercalation compounds increased to 1.437 nm from 0.717
      nm of kaolinite. The analysis of FTIR shows that intercalation caused the shifts
      of the inner surface OH stretching bands from 3 696 and 3 657 cm(-1) of the raw
      kaolinite to 3 701 and 3 651 cm(-1) of the kaolinite-benzamide intercalation
      compounds, respectively, and the blue shift of C=O stretching bands from 1 659
      cm(-1) of benzamdie to 1 640 cm(-1) of the kaolinite-benzamide intercalation
      compounds, and the NH vibrations at 3 368 and 3 172 cm(-1) of benzamdie shifted
      to 3 474 and 3 184 cm(-1), respectively. These changes in IR bands implied the
      breaking of the H-bonds between layers of kaolinite and the formation of new H
      bonds between the inner-surface hydroxyls of the kaolinite and the benzamide in
      the intercalation compounds. The experimental results show that the intercalation
      reaction comes to equilibrium rapidly during 30 min, and the highest
      intercalation ratio occurs when the reaction temperature is 180 degrees C. Washed
      by acetone, the residual benzamide and that adsorbed on the surface of the
      resulting products could be eliminated without significant influence on the
      structure of the intercalation compounds.

PMID- 19839310
TI  - [Research on static Fourier interferometer in target identification].
AB  - A new method was proposed for target identification with static Fourier
      interferometer. Considering the complex structure of mechanical scanning
      interferometer and the poor stability of identification, a remote detection
      technique for target identification based on the static spectrum analysis is
      proposed. Using the static scanning technique to replace mechanical scanning of
      optical path and applying spectrum analysis method to analyze the interference
      fringes, the target identification in the bad environment in the wide range field
      of view was realized. By the simulation computation, the present work obtained
      the spectro-radiometric function with temperature, wavelength and the air
      transmittance as the parameters, and got the characteristic of data from
      difference background radiation. The spectrum D-value function shows the energy
      of the spectrum in different situation. Performing experiments with the AViiVA-M2
      CCD camera, Static Fourier Interferometer, and 1 m x 1 m iron-sheet as the target
      separately at different time in one day, with different probing range, and under
      different background condition, the limited distance in each situation was
      obtained by the system. According to the result of experiment and spectrum data
      analysis, the target identification method with difference spectrum is feasible,
      and the average probability of detection is 92.8%.

PMID- 19839311
TI  - [Determination of soil quality from Chinese apple plant area by NIR
      spectroscopy].
AB  - In the present work, 111 soil samples from 11 different Chinese apple plant areas
      were used to take the diffuse reflection spectra from 12 500 to 4 000 cm(-1) by
      FT-NIR. The models of organic substance and pH value of soil samples were built
      by using partial least square regression (PLSR). The calibration model gave the
      correlation coefficients of 0.818 and 0.836 for the two values respectively, with
      the root mean square error of prediction (RMSEP) of 0.377 (%) and 0.251,
      respectively. In order to improve the robustness and performance of calibration,
      several spectra preprocessing methods were employed, including standard
      normalized variate (SNV), multiplicative scatter correction (MSC) and direct
      orthogonal signal correction (DOSC). Finally, the performance of DOSC was found
      to be the best for organic substance and pH value with RMSEP of 0.258 (%) an
      0.248, respectively. The results showed that the technology of NIR spectroscopy
      was useful to nondestructive determination of the organic substance and pH value
      of soil. These research findings provide theoretic base for fertilization and
      pomiculture by means of NIR diffuse reflection.

PMID- 19839312
TI  - [Detection of fatty acid composition in intramuscular fat of packed pork loin by
      near infrared spectroscopy].
AB  - Near infrared spectroscopy as a new method was proposed for rapid and non
      destructive measurement of fatty acid composition in intramuscular fat of packed
      pork loin. Gas chromatography was used as a reference method for the spectral
      analysis of fatty acid composition. The fiber optic in interactance mode was
      adopted to measure the spectra of packed pork loins by low density polythene. The
      original spectra were pretreated by smoothing and 2nd derivative, and then PLS
      calibration model was builtby using software of Unscrambler 9.6. A total of
      eighty two samples were used in the experiment. The samples were divided into
      calibration set and validation set after removing the outliers. The calibration
      set was used to set up calibration model and then the model was adopted to
      predict the samples of validation set. The results show that the correlation
      coefficient for C14 : 0, C15 : 1, C16 : 0, C16 : 1, C18 : 0, C18 : 1, C18 : 2,
      C18 : 3, C20 : 1, C20 : 4, SFA, MUFA, PUFA is 0.57, 0.76, 0.71, 0.77, 0.62, 0.81,
      0.86, 0.91, 0.85, 0.91, 0.67, 0.81 and 0.95, respectively. It means that
      evaluating fatty acid using near infrared spectroscopy in interactance mode has
      higher precision. Near infrared spectroscopy technique is a feasible and rapid
      method for nondestructive detection of fatty acid composition in intramuscular
      fat of packed pork loin.

PMID- 19839313
TI  - [Detection of the main quality indicators in red wine with infrared spectroscopy
      based on FastICA and neural network].
AB  - For the rapid detection of the ethanol, pH and rest sugar in red wine, infrared
      (IR) spectra of 44 wine samples were analyzed. The algorithm of fast independent
      component analysis (FastICA) was used to decompose the data of IR spectra, and
      their independent components and the mixing matrix were obtained. Then, the ICA
      NNR calibration model with three-level artificial neural network (ANN) structure
      was built by using back-propagation (BP) algorithm. The models were used to
      estimate the contents of ethanol, pH and rest sugar in red wine samples for both
      in calibration set and predicted set. Correlation coefficient (r) of prediction
      and root mean square error of prediction (RMSEP) were used as the evaluation
      indexes. The results indicate that the r and RMSEP for the prediction of ethanol
      content, pH and rest sugar content are 0.953, 0.983 and 0.994, and 0.161, 0.017
      and 0.181, respectively. The maximum relative deviations between the ICA-NNR
      method predicted value and referenced value of the 22 samples in predicted set
      are less than 4%. The results of this paper provide a foundation for the
      application and further development of IR on-line red wine analyzer.

PMID- 19839314
TI  - [Exploratory research on quantitative analysis of gaseous mixtures by AOTF-NIR
      spectrometer].
AB  - Due to its many advantages, such as miniaturization, high accuracy, high
      resolution, fast scanning speed, increased robustness and good stability, acousto
      optic tunable filter (AOTF)-near infrared (NIR) spectrometer has been
      successfully applied in many fields. However, up to now, the commercial AOTF-NIR
      spectrometers can only be used for liquid and solid detection, but not for the
      detection of gaseous samples. In the present paper, the feasibility of
      quantitative analysis of gaseous mixtures by using AOTF-NIR spectrometer was
      investigated. A homemade gas cell was assembled to an AOTF-NIR spectrometer with
      probe for liquid detection to obtain NIR spectra of detected gas samples. The gas
      samples were composed of two groups: single-component CH4 and ternary component
      gaseous mixture of CH4, C2 H6, and C3 H8. The detection ability of fitted AOTF
      NIR spectrometer was tested firstly. Comparing the absorption spectra of various
      concentrations, the absorbance of CH4 in absorption bands obviously increased
      with concentration increasing when the concentration was over 0.1%. According to
      the detection results, the lower limit of detection (LLD) of the AOTF-NIR
      spectrometer with gas cell was estimated to be 898 microL x L(-1). Subsequently,
      the NIR spectra of ternary mixtures were collected. The kernel partial least
      squares (KPLS) regression was employed to create the quantitative analysis model
      of three components gases. To evaluate the analysis ability of KPLS model, the
      PLS model was also created. The prediction results of the identical testing set
      show that the root mean square error of prediction (RMSEP) of three components
      predicted by KPLS model was 1.08%, 0.87%, and 0.79%, respectively, less than the
      RMSEP by PLS model. The exploratory work indicates that accurate quantitative
      analysis of ternary component alkane gaseous mixtures can be achieved by fitted
      AOTF-NIR spectrometer despite of some limitations, and KPLS regression is an
      excellent approach to NIR spectra analysis.

PMID- 19839315
TI  - [Common and variant peak ratios in IR fingerprint of Cacumen platycladi with dual
      index sequence analysis].
AB  - To establish a new method to analyze IR fingerprint, which is in line with the
      characteristic of traditional Chinese medicine, two indexes, common peak ratio
      and variant peak ratio, were applied and their values were calculated by means of
      sequential analysis, in which each Cacumen platycladi sample's IR fingerprint
      spectra were set up and the common peak ratio sequences were arranged in the
      order of size in comparison with other samples. The analytical results showed
      that samples G1 and G8 from the same region, and G4, G2 and G6 from the closer
      regions were the most similar samples with higher common peak ratio (> or =
      90.0%) and lower variant peak ratio (< or = 11.1%). However, the samples G10, G3,
      G4 and G5 from the closer regions collected in different years, and G2 and G7
      from the farther regions,were of significant disparity with common peak ratio
      less than 50% and variant peak ratio larger than 50%. As a result, the method
      could be used to distinguish Cacumen platycladi of different areas and batches.
      The dual index sequential analysis enables us to distinguish two or more herb's
      IR fingerprints, is a new method to analyze IR fingerprint spectra, and can be
      used in line with the characteristics of traditional Chinese medicine.

PMID- 19839316
TI  - [Measuring and analyzing infrared spectrum of periodically polarized lithium
      niobate].
AB  - The present paper reports theoretical and experimental research on the tunable
      output characteristics of periodically polarized lithium niobate. We made six
      equal distance crystal grating sections, with each distance being 0.5 mm and the
      polarization period range of 29.0-31.5 mm. Especially, at room temperature, the
      signal-wavelength tunable output in the range of 1 449.7-1 665.0 nm and idle
      wavelength tunable output in the range of 3 989.2-2 946.0 nm were achieved by LD
      end-pumped Nd : YVO4 laser with Q-switch in sound-wave. The lowest excitation
      threshold was 108.0 mW, while the highest excitation threshold was 149.2 mW. When
      the pump power was 649 mW, the highest gained signal-wave output was 118.5 mW and
      its conversion efficiency was 18.26%. Meanwhile, the idle-wave output was 46.6 mW
      and its conversion efficiency was 7.18%. These parameters approached the
      practicality level.

PMID- 19839317
TI  - [Rapid determination of the components in ternary blended edible oil using near
      infrared transmission spectroscopy].
AB  - The FT-NIR transmission spectra of ternary blended edible oil samples were
      collected over 10 000-4 200 cm(-1). After being pretreated with different
      methods, the calibration models of quantitative analysis of soybean oil, peanut
      oil and corn oil contents in ternary blended edible oil were established using
      partial least square (PLS) regression. The accuracy and precision of the models
      for the predicted sample set were examined to make sure of the practicability of
      the models. After being pretreated with first derivative and multiplicative
      signal correction (FD+MSC), the optimal soybean oil NIR model was built over 5
      450.1-4 597.7 cm(-1). The best prediction model for peanut oil was established
      between 7 521.3 and 6 098.1 cm(-1) after using first derivative with straight
      line subtraction (FD+SLS) preprocess method. The best pretreated method and the
      best spectrum range for corn oil content model were first derivative (FD) and 9
      993.7-7 498.2 cm(-1), respectively. The best correlation coefficients (R2) of the
      three prediction models were 99.89%, 99.88% and 99.76%, respectively. The RMSEP
      of the soybean oil content model was 1.09%, while the peanut oil prediction
      model's RMSEP was 1.17%, and 1.48% for the corn oil prediction model. The values
      of the t-test were between 0.007 9 and 0.371 9, and all values of the relative
      standard deviation (RSD) were less than 1.50%. The results showed that NIR could
      be an ideal tool for fast determination of the soybean oil, peanut oil and corn
      oil contents in ternary blended edible oil.

PMID- 19839318
TI  - [The progress in retrieving land surface temperature based on thermal infrared
      and microwave remote sensing technologies].
AB  - Land surface temperature (LST) is an important parameter in the study on the
      exchange of substance and energy between land surface and air for the land
      surface physics process at regional and global scales. Many applications of
      satellites remotely sensed data must provide exact and quantificational LST, such
      as drought, high temperature, forest fire, earthquake, hydrology and the
      vegetation monitor, and the models of global circulation and regional climate
      also need LST as input parameter. Therefore, the retrieval of LST using remote
      sensing technology becomes one of the key tasks in quantificational remote
      sensing study. Normally, in the spectrum bands, the thermal infrared (TIR, 3-15
      microm) and microwave bands (1 mm-1 m) are important for retrieval of the LST. In
      the present paper, firstly, several methods for estimating the LST on the basis
      of thermal infrared (TIR) remote sensing were synthetically reviewed, i. e., the
      LST measured with an ground-base infrared thermometer, the LST retrieval from
      mono-window algorithm (MWA), single-channel algorithm (SCA), split-window
      techniques (SWT) and multi-channels algorithm(MCA), single-channel & multi-angle
      algorithm and multi-channels algorithm & multi-angle algorithm, and retrieval
      method of land surface component temperature using thermal infrared remotely
      sensed satellite observation. Secondly, the study status of land surface
      emissivity (epsilon) was presented. Thirdly, in order to retrieve LST for all
      weather conditions, microwave remotely sensed data, instead of thermal infrared
      data, have been developed recently, and the LST retrieval method from passive
      microwave remotely sensed data was also introduced. Finally, the main merits and
      shortcomings of different kinds of LST retrieval methods were discussed,
      respectively.

PMID- 19839319
TI  - [Low-temperature-dependent Raman study on A1 (LO) mode of 6H-SiC].
AB  - Variable temperature method was lent for low temperature Raman study on bulk
      monocrystal 6H-SiC in the temperature range from 80 to 320 K. Some Raman folding
      modes of 6H-SiC were assigned in the spectrum. The peak position and line width
      of optical phonon A1 (LO) versus temperature mainly below RT was focused on by 3
      phonon and 4-phonon models. The result showed that as the temperature decreased
      the line width decreased, while the peak position shifted to high wave number. It
      was found that as the temperature varied below 160 K, the change in peak position
      and line width was little, different from it was at RT, revealing that the line
      type of A1 (LO) mode was mainly decided by the phonon characteristics and the
      effect of temperature could be ignored when it was below 160 K. It was showed
      that 4-phonon model was closer to the experiment data for fitting. Both the third
      and forth anharmonic vibration contributed to the spectrum, while the former was
      the main process. Moreover, the phonon lifetime became longer when the
      temperature fell because of the decrease in the atomic thermal motion.

PMID- 19839320
TI  - [Study on structure and phase transformation laws of natural FeS2 whisker by
      Raman spectroscopy].
AB  - FeS2 belongs to sulfide, including pyrite of isometric system and marcasite of
      orthorhombic system. The FeS2 discovered in Gengzhuang, Shanxi Province, was
      growing in the form of whisker. The study with scanning electron microscopy and
      electron probe show that the mineral components of FeS2 vary regularly. The
      structure of natural nano-micron FeS2 whisker was determined by micro-Raman
      spectroscopy. The results show that there exist two types of structure in FeS2
      whiskers: pyrite and marcasite. Marcasite presents irregular shapes, such as
      coarse lotus root joints, crude columnar or beaded. Pyrite exists in the shape of
      straight line and smooth surface. In the early growing stage, Gengzhuang FeS2
      whisker was mainly marcasite-type structure; in the middle stage it was
      coexistent structure of pyrite- and marcasite-type; in the late stage it was
      mainly pyrite-type. The growing stages of the whisker FeS2 show the phase
      transformation laws. Moreover, during the growing process marcasite was growing
      with pyrite coated on. Study on FeS2 whisker structure shows that there are
      correlations between phase transformation laws of the structure and forms, and
      between the forming time and the composition characteristics.

PMID- 19839321
TI  - [The effect of abnormal cell shape on the spectral distinguishing of erythrocytes
      using laser tweezers Raman spectroscopy].
AB  - Erythrocyte is a mature blood cell that contains hemoglobin to carry oxygen to
      the bodily tissues. Erythrocyte, which takes on a biconcave disc that has no
      nucleus, is flexible and changeful. Erythrocyte is so sensitive to the
      environment that the shape of cell goes crimpy, even acanthoid. A laser tweezers
      Raman spectroscopy (LTRS) setup was used to trap single erythrocyte from healthy
      donors and patients with thalassemia and to collect the Raman scattering of
      trapping cell. Normal shape, crimpy erythrocytes and acanthoid erythrocytes were
      tested, and the averaged spectra, and principal component analysis (PCA) which
      detailed the spectral difference and the change of hemoglobin, were used to
      evaluate the effects of different cell shape on the spectral distinguishing of
      erythrocyte. The results reveal that in normal physiological environment the
      change in cell shape does not effect the spectral distinguishing of abnormal
      erythrocyte.

PMID- 19839322
TI  - [Spectral analysis of polyphenol oxidase (PPO) and lipoxygenase (LOX) treated by
      pulsed electric field].
AB  - Inactivation effect of pulsed electric field (PEF) on polyphenol oxidase (PPO)
      and lipoxygenase (LOX) was investigated using a laboratory PEF system with a
      coaxial treatment chamber. Circular dichroism (CD) and fluorescence analysis were
      used to study the conformation change of the protein. The experimental results
      show that PPO and LOX can be effectively inactivated by the PEF treatment.
      Inactivation effect of PPO and LOX increases with the increase in the applied
      electric strength and the treatment time. Activity of PPO and LOX can be reduced
      by 60.3% and 21.7% at 20 kV x cm(-1) after being treated for 320 micros
      respectively. The decrease of the negative peaks (208 and 215 nm in PPO spectra,
      208 nm and 218 nm in LOX spectra) in CD spectra of PPO and LOX shows that PEF
      treatment caused a loss of alpha-helix and increase in beta-sheet content,
      indicating that conformation changes occur in the secondary structure of PPO and
      LOX enzyme. This effect was strengthened as the applied electric field increased:
      alpha-helical content of PPO and LOX was 56% and 29% after being treated at 8 kV
      x cm(-1), however, when the electric field was increased up to 20 kV x cm(-1),
      alpha-helical content of PPO and LOX decreased to 21% and 16% respectively. The
      decrease rate of alpha-helix and increase rate of beta-sheet in PPO are higher
      than LOX, indicating that the second conformation of PPO is less resistant to PEF
      treatment than LOX. The fluorescence intensity of LOX increases after PEF
      treatment. At the same time, increasing the applied pulsed electric field
      increases the fluorescence intensity emitted. Fluorescence measurements confirm
      that tertiary conformation changes occur in the local structure of LOX. However
      the possible mechanism of the conformation change induced by the PEF treatment is
      beyond the scope of the present investigation.

PMID- 19839323
TI  - [The effect of spectral range on the measurement of ozone in the atmosphere by
      DOAS].
AB  - Ozone (O3) often serves as the benchmark for the overall pollution level of a
      given airshed and it is critical that the measurement technique be accurate and
      precise, In the DOAS measurement, the accuracy of O3 concentration is determined
      by the selected spectral range. The present paper focuses on the effect of
      spectral range on the detected characteristic absorption structure of O3, and the
      variation of differential cross section of O3 with the change in spectral range
      and the source of interference in different spectral range. The effect of
      practical atmospheric light extinction on the light intensities of different
      spectral ranges was deduced; the effect of spectral range on the accuracy was
      determined by detecting the standard gases at different concentration and
      different spectral resolution. The optimized spectral range was determined for
      O3, which can yield high sensitivity, good selectivity and a reasonable time
      resolution for the accurate qualitative and quantitative analysis of O3.

PMID- 19839324
TI  - [Urban land use change detection based on high accuracy classification of
      multispectral remote sensing imagery].
AB  - In the present paper, the urban land change in Jiading district of Shanghai was
      studied on the basis of high accuracy classification for 4 epochs of
      multispectral remotely sensed imageries. A further improved genetic-algorithm
      optimized back propagation neural network approach was first employed in our
      study to obtain sorts of land cover types from the remotely sensed imageries. The
      urban land and non-urban land types were thus extracted based on the
      classification result. According to the 16 corresponding relationships between
      the pixel values in the four urban land imageries and the ones in the generated
      urban land change imagery, the amount of each type pixel in the generated imagery
      was calculated according to the four plates, and the situation of urban land
      change was analyzed and investigated for the study area in three year intervals.
      The urban development in the study area was also preliminarily revealed.

PMID- 19839325
TI  - [Using fractal dimensions of hyperspectral curves to analyze the healthy status
      of vegetation].
AB  - The reflectance spectral curves of leaves can reflect many information of
      vegetation growth, and its variation maybe means that the healthy status of
      vegetation will change. Many spectral feature parameters such as red edge
      position, height of green peak, depth of red band absorption, the area of red
      edge and some vegetation index have been used to describe this change. However,
      the change of vegetation healthy status is not some feature parameters, but a
      comprehensive variation of the whole curve. So, a comprehensive index maybe has
      more value to describe the change of hyperspectral curve of vegetation and
      indicates its healthy status. Fractal is an appropriate mathematical tool, and
      fractal dimension can be used to explain the comprehensive variation of a curve.
      Therefore, in the present study, fractal theory was used to analyze the healthy
      status of different vegetation. Firstly, analytical spectral devices (ASD) were
      used to measure the hyperspectral curves of different vegetations with different
      healthy status. Secondly, spectral curves were analyzed, and some parameters
      which can really reflect different healthy status were obtained. Finally, the
      fractal dimension of reflectance spectral curves inside a spectral band zone
      between 450 and 780nm was computed by variation method, and the relationship
      between fractal dimensions and spectral feature parameters was established. The
      research results showed that (1) the hyperspectral curves of vegetation have
      fractal feature, and their fractal dimensions gradually decrease with the health
      deterioration of leaves, (2) fractal dimension has positive correlation with the
      height of green peak, the depth of red band absorption and the area of red edge,
      (3) multivariate analysis showed that fractal dimensions have a significant
      linear relationship with the three spectral feature parameters just mentioned
      above. So, the fractal dimension of hyperspectral curve can serve as a new
      comprehensive parameter to analyze quantitatively the healthy status of
      vegetations.

PMID- 19839326
TI  - [The research on bidirectional reflectance computer simulation of forest canopy
      at pixel scale].
AB  - Computer simulation is based on computer graphics to generate the realistic 3D
      structure scene of vegetation, and to simulate the canopy regime using radiosity
      method. In the present paper, the authors expand the computer simulation model to
      simulate forest canopy bidirectional reflectance at pixel scale. But usually, the
      trees are complex structures, which are tall and have many branches. So there is
      almost a need for hundreds of thousands or even millions of facets to built up
      the realistic structure scene for the forest It is difficult for the radiosity
      method to compute so many facets. In order to make the radiosity method to
      simulate the forest scene at pixel scale, in the authors' research, the authors
      proposed one idea to simplify the structure of forest crowns, and abstract the
      crowns to ellipsoids. And based on the optical characteristics of the tree
      component and the characteristics of the internal energy transmission of photon
      in real crown, the authors valued the optical characteristics of ellipsoid
      surface facets. In the computer simulation of the forest, with the idea of
      geometrical optics model, the gap model is considered to get the forest canopy
      bidirectional reflectance at pixel scale. Comparing the computer simulation
      results with the GOMS model, and Multi-angle Imaging SpectroRadiometer (MISR)
      multi-angle remote sensing data, the simulation results are in agreement with the
      GOMS simulation result and MISR BRF. But there are also some problems to be
      solved. So the authors can conclude that the study has important value for the
      application of multi-angle remote sensing and the inversion of vegetation canopy
      structure parameters.

PMID- 19839327
TI  - [Study on the pH-sensitive secondary structure of gamma-PGA embedded with
      magnetite nanoparticles].
AB  - The conformational transition of poly gamma-glutamic acid (gamma-PGA) embedded
      with magnetite nanoparticles under various pH conditions was investigated by
      Fourier transform infrared spectroscopy (FTIR). The secondary structure content
      was determined through the analysis of amide I bands of Fourier deconvolution
      spectra, secondary derivative spectra and the Gaussian curve fitting of the
      original infrared spectra. The results showed that the conformation of the gamma
      PGA was affected by solution pH. The total contents of beta-sheet and beta-turn
      were higher than 65%, while alpha-helix and random coil were low. The content of
      beta-turn increased with increasing pH, while the beta-sheet decreased.
      Additionally, the zeta potential results showed that the pH-sensitive secondary
      structure of gamma-PGA had influence on the stability of suspension of magnetic
      gamma-PGA nanospheres. The minimum value of zeta potential (-35. 4 mV) was
      obtained at pH 10.2.

PMID- 19839328
TI  - [Compositions and structure characterizations of coal tar refined soft pitch].
AB  - High temperature coal tar was used as raw materials, and was distilled to 280
      degrees C for getting coal tar soft pitch. Then refined soft pitch was obtained
      by solvent extracting and subsequent settlement method. Its soft point was 32
      degrees C; the group compositions consisted of 53.67% heptane soluble, 39.47%
      heptane insoluble but toluene soluble, 6.86% toluene insoluble and 0.06%
      quinoline insoluble. The relative average molecular weight was about 292. Its
      average molecular formula was C22.22 H16.32 N0.12 S0.06 O0.33; the total content
      of heteroatom was less than 1. IR analytic results showed that its heteroatom O
      existed in the R-O-R and Ar-O-R structure; its heteroatom N existed in the R-NH-R
      and -N=, with the latter being primary. Its average structure was obtained by
      improved Brown-Lander model: five-membered condensed rings. UV analysis indicated
      that the majority was linear arrangement, and the minority was surface
      arrangement; namely, the chemical structure of the samples was mainly the cata
      condensed structure, while the minority was peri-condensation.

PMID- 19839329
TI  - [Relationship between the laccase production of Pleurotus ostreatus and the full
      wavelength scan for the fermentation liquid].
AB  - Laccase, widely distributed in fungi lacking high substrate specificity, plays an
      important role in lignin degradation in nature and environmental protection. In
      order to determine or estimate the laccase production during the fermentation of
      liquid media, the authors studied the full-length wave scan on the rough
      fermentation liquid of the Pleurotus ostreatus, which produces laccase high.
      Combined with the normal chemical method and diameter of the laccase and mycelium
      stain, which grew on the PDA (potato dextrose agar) plate with guaiacol added, we
      could get the exact information of laccase production. The result showed that the
      laccase activity increased in a rapid way in the first 5 days during the
      fermentation process, remained almost at the same level in the following 4 days,
      then increased rapidly until the 11 day, which was 148.7 U x L(-1), increased
      17.9 times. The diameter of laccase and mycelium stain increased with the culture
      time. The number of the wave peaks around 300 nm had a positive correlation with
      the laccase production; the peak width of OD over 1.5 around 300 nm had a
      positive correlation with the laccase production, which ranges from 5 nm on the
      first day to 80 nm on the 11th day. The light absorption line between the
      wavelengths 300 and 400 nm had a positive correlation with the laccase production
      with peaks at 349, 365 and 388 nm, and at 365 the peak gets its highest. Using
      these parameters, the authors could get the general production of the laccase
      production of liquid fermentation. Compared with the normal chemical method, the
      full-length wave scan method is much easier, cheap and simple. Furthermore, there
      are no special chemical substances used. It is really a new method for the
      evaluation and determination of laccase.

PMID- 19839330
TI  - [Comparison of principal component analysis with VI-empirical approach for
      estimating severity of yellow rust of winter wheat].
AB  - The canopy reflectance of winter wheat infected by yellow rust with different
      severity was measured through artificial inoculation, and the disease index (DI)
      of the wheat corresponding to the spectra acquired in the field was obtained.
      Principal component analysis (PCA) was used to compute the first 5 principal
      components (PCs) of canopy spectra in the 350-1 350 nm range and the first 3 PCs
      of first-order derivative in blue edge (490-530 nm), yellow edge (550-582 nm) and
      red edge (630-673 nm), respectively. Step-wise regression was used to build
      models, the results of those models are compared with that of VI-empirical
      models, and the result shows that the model based on PCs of first-order
      derivative is particularly accurate compared to others, with the RMSE of 7.65 and
      relative error of 15.59%. Comparison was made between the estimated DI and the
      measured DI, indicating that the model based on SDr'/SDg' is suitable to
      monitoring early disease and the model based on PCs of first-order derivative is
      suitable to monitoring the more severe disease of yellow rust of winter wheat.
      The conclusion has great practical and application value to acquiring and
      evaluating wheat disease severity using hyperspectral remote sensing, and has an
      important meaning for increasing yields of crops and ensuring security of food
      supplies.

PMID- 19839331
TI  - [Studies on Ag-TiO2/KIT-6 composite nanosized photocatalyst].
AB  - In the present paper, ordered mesoporous silica (KIT-6) as support, nanosized
      TiO2 into KIT-6 was synthesized by titanium tetraisopropoxide hydrolysis. Then
      silver was loaded by deposition-precipitation method. Ag-TiO2/KIT-6 composite
      nanosized photocatalyst was firstly synthesized and a series of correlated
      catalysts were synthesized by the same preparation method. Methyl orange is
      presently adopted as a representative organic pollutant to evaluate the
      photocatalytic performance of the as-synthesized catalysts. The order of
      photocatalytic activity of the as-synthesized samples was found as Ag-TiO2/KIT-6
      > Ag/TiO2 > TiO2/KIT-6 > TiO2 > Ag/KIT-6. Detailed characterizations were
      conducted by techniques including XRD, N2 physical adsorption, XPS, UV-Vis DRS
      and TEM. It was found that the Ag-TiO2 /KIT-6 sample shows the highest
      photocatalytic activity, which should be attributed to the Ag-TiO2 heterojunction
      structure and higher BET surface area of the Ag-TiO2/KIT-6 sample. Ag-TiO2
      heterojunction improves the separation of photogenerated electron-hole pairs,
      thus enhancing the photocatalytic activity; Ag-TiO2/KIT-6 sample possesses high
      BET surface area, which facilitates adsorption and transportation of dye
      molecules, also leading to higher photocatalytic activity.

PMID- 19839332
TI  - [Diagnoses of rice nitrogen status based on characteristics of scanning leaf].
AB  - In the present research, the scanner was adopted as the digital image sensor, and
      a new method to diagnose the status of rice based on image processing technology
      was established. The main results are as follows: (1) According to the analysis
      of relations between leaf percentage nitrogen contents and color parameter, the
      sensitive color parameters were abstracted as B, b, b/(r+g), b/r and b/g. The
      leaf position (vertical spatial variation) effects on leaf chlorophyll contents
      were investigated, and the third fully expanded leaf was selected as the
      diagnosis leaf. (2) Field ground data such as ASD were collected simultaneously.
      Then study on the relationships between scanned leaf color characteristics and
      hyperspectral was carried out. The results indicated that the diagnosis of
      nitrogen status based on the scanned color characteristic is able to partly
      reflect the hyperspectral properties. (3) The leaf color and shape features were
      intergrated and the model of diagnosing the status of rice was established with
      calculated at YIQ color system. The distinct accuracy of nitrogen status was as
      follows: N0: 74.9%; N1 : 52%; N2 : 84.7%; N3 : 75%. The preliminary study showed
      that the methodology has been proved successful in this study and provides the
      potential to monitor nitrogen status in a cost-effective and accurate way based
      on the scanned digital image. Although, some confusion exists, with rapidly
      increasing resolution of digital platform and development of digital image
      technology, it will be more convenient for larger farms that can afford to use
      mechanized systems for site-specific nutrient management. Moreover, deeper theory
      research and practice experiment should be needed in the future.

PMID- 19839333
TI  - [Nitrogen status diagnosis of rice by using a digital camera].
AB  - In the present research, a field experiment with different N application rate was
      conducted to study the possibility of using visible band color analysis methods
      to monitor the N status of rice canopy. The Correlations of visible spectrum band
      color intensity between rice canopy image acquired from a digital camera and
      conventional nitrogen status diagnosis parameters of leaf SPAD chlorophyll meter
      readings, total N content, upland biomass and N uptake were studied. The results
      showed that the red color intensity (R), green color intensity (G) and normalized
      redness intensity (NRI) have significant inverse linear correlations with the
      conventional N diagnosis parameters of SPAD readings, total N content, upland
      biomass and total N uptake. The correlation coefficient values (r) were from 
      0.561 to -0.714 for red band (R), from -0.452 to -0.505 for green band (G), and
      from -0.541 to 0.817 for normalized redness intensity (NRI). But the normalized
      greenness intensity (NGI) showed a significant positive correlation with
      conventional N parameters and the correlation coefficient values (r) were from
      0.505 to 0.559. Compared with SPAD readings, the normalized redness intensity
      (NRI), with a high r value of 0.541-0.780 with conventional N parameters, could
      better express the N status of rice. The digital image color analysis method
      showed the potential of being used in rice N status diagnosis in the future.

PMID- 19839334
TI  - [Decoloration and degradation of rhodamine B by microwave-promoted Fenton-like
      reaction].
AB  - Microwave-promoted Fenton-like reaction, the combination of Fenton-like reagent
      with microwave, is an efficient method for waste water treatment. In the present
      paper, the degradation of rhodamine B (a kind of organic dye) using this method
      was studied. Through numerous experiments, the influences of various parameters
      including the initial pH value, reaction time, dosage of K2Cr2O7, dosage of H2O2
      and microwave were investigated intensively. The characteristic curve of
      rhodamine B, the concentration-absorbency curve of rhodamine B, the orthogonal
      optimization tests and comparative tests were given. The mechanism of this
      reaction was also probed. It is concluded from the experiments that the microwave
      can accelerate the process of degradation effectively. Under optimal conditions,
      the overall color removal was more than 99.9% within 9 min. In the study, the
      method for characterization was entirely UV-Vis spectral analysis.

PMID- 19839335
TI  - [La-Ce-Codoping nano-titania photocatalyst: preparation via microwave-assisted
      sol process, spectroscopy characterization and photocatalytic activity].
AB  - La-Ce codoping nano-TiO2 catalyst was prepared by microwave-assisted sol process
      with TBT and distilled water as forerunner body, ethanol as solvent and glacial
      acetic acid as inhibitor. The prepared samples were characterized by using XRD,
      XPS and UV-Vis techniques. Results of structural characterization indicated that
      the prepared samples were all pure anatase phase nano-TiO2 and their diffraction
      peak broadened obviously after La and Ce doping. Results of XPS analysis revealed
      that La-O bond existed in the samples and many oxygen vacancies were produced on
      the surface of TiO2 nanoparticles after La and Ce codoping. UV-Vis absorption
      spectra demonstrated that the prepared samples had strong and wide absorption
      band between 200 and 400 nm and the absorption intensity increased after La and
      Ce doping because of La(III)-O charge-transfer transition, Ce (IV) f --> d
      transition and Ce (IV)-O charge-transfer transition. Photocatalytic experiment
      results showed that the titanium dioxide's photocatalytic activity increased
      obviously after La and Ce codoping. The optimal parameters for the preparation
      were obtained by adjusting the mole ratio of La and Ce in photocatalysts. When
      the doping amount of La and Ce was 2% and 0.04% respectively, the prepared sample
      exhibited high photocatalytic activity, the decoloration ratio of methyl orange
      solution was above 90%, and COD removal of cigarette factory wastewater was
      86.11%.

PMID- 19839336
TI  - [Exploring novel hyperspectral band and key index for leaf nitrogen accumulation
      in wheat].
AB  - The objectives of the present study were to explore new sensitive spectral bands
      and ratio spectral indices based on precise analysis of ground-based
      hyperspectral information, and then develop regression model for estimating leaf
      N accumulation per unit soil area (LNA) in winter wheat (Triticum aestivum L.).
      Three field experiments were conducted with different N rates and cultivar types
      in three consecutive growing seasons, and time-course measurements were taken on
      canopy hyperspectral reflectance and LNA tinder the various treatments. By
      adopting the method of reduced precise sampling, the detailed ratio spectral
      indices (RSI) within the range of 350-2 500 nm were constructed, and the
      quantitative relationships between LNA (gN m(-2)) and RSI (i, j) were analyzed.
      It was found that several key spectral bands and spectral indices were suitable
      for estimating LNA in wheat, and the spectral parameter RSI (990, 720) was the
      most reliable indicator for LNA in wheat. The regression model based on the best
      RSI was formulated as y = 5.095x - 6.040, with R2 of 0.814. From testing of the
      derived equations with independent experiment data, the model on RSI (990, 720)
      had R2 of 0.847 and RRMSE of 24.7%. Thus, it is concluded that the present
      hyperspectral parameter of RSI (990, 720) and derived regression model can be
      reliably used for estimating LNA in winter wheat. These results provide the
      feasible key bands and technical basis for developing the portable instrument of
      monitoring wheat nitrogen status and for extracting useful spectral information
      from remote sensing images.

PMID- 19839337
TI  - [A spectral analysis method for total volatile base nitrogen].
AB  - A new method for the determination of the total volatile basic nitrogen (TVB-N)
      by reflectance spectroscopy was developed. The method was based on the reaction
      of TVB-N with Nessler's reagent treated by molecular sieve and the reflectance
      absorption value F(R), which is directly proportional to the amount of NH2 Hg IO
      in solid phase, was measured by the reflection spectrometer. The fundamental
      principle, effective factors and experimental conditions of the method were
      discussed. The special features of this method were its simplicity in operation,
      relatively high sensitivity of determination and the use of a small amount of
      reagent. Linear calibration graph was obtained in the range 1-8 microg x mL(-1)
      with a detection limit of 0.1 microg x mL(-1). The method was applied to monitor
      the fresh degree of fish and pork. The result discovered that the total volatile
      basic nitrogen increased rapidly along with the time extension, indicating that
      the deterioration of fish and pork was an acceleration process, and the
      deterioration speed of fish was faster than that of pork.

PMID- 19839338
TI  - [Study on the interaction of Sm(III) complexes of rutin with serum albumin].
AB  - The binding reaction of rutin-Sm with serum albumin (SA) was investigated by the
      fluorescence method in physiological condition. The authors studied mainly the
      quenching mechanism of the fluorescence of SA by rutin-Sm, and calculation of the
      binding constants K(LB) of human serum albumin (HSA) and bovine serum albumin
      (BSA) with rutin-Sm by Lineweaver-Burk equation at different temperatures
      respectively, then obtained the thermodynamic parameters of HSA and BSA with
      rutin-Sm according to the calculated binding constants K(LB) at different
      temperature, meanwhile the type of binding forces of HSA and BSA with rutin-Sm
      was determined. The results showed that the emission spectra of BSA (HSA) in the
      presence and absence of rutin-Sm are different. The emission spectra of BSA (HSA)
      in the presence of rutin-Sm can be quenched. The quenching mechanism of rutin-Sm
      to SA was static quenching with non-radiation energy transfer for new complex of
      SA and rutin-Sm. The binding constants K(LB) (L x moL(-1)) were 6.540 x 10(5) and
      3.265 x 10(5) for BSA, and 6.830 x 10(5) and 4.665 x 10(5) for HSA at 295 K and
      310 K respectively. And the type of bonding forces was estimated by the
      calculation of thermodynamic parameters of the reaction of rutin-Sm with SA at
      different temperatures, and the result showed that the binding forces were mainly
      H-bond and Van der Waals between BSA and rutin-Sm due to the deltaH < 0 and
      deltaS < 0, and the main electrostatic interaction of rutin-Sm and HSA because of
      deltaH < 0 and deltaS > 0. The effect of rutin-Sm on the conformation of serum
      albumin was also studied by using synchronous fluorescence spectroscopy. Results
      indicated that rutin-Sm could be deposited and transported by serum protein in
      vivo.

PMID- 19839339
TI  - [Fluorescence spectroscopic chracterization of the complexation between
      mercury(II) and dissolved organic matter].
AB  - In this study, conventional fluorescence spectroscopy in the excitation, emission
      and synchronous scan modes and three-dimensional fluorescence spectroscopy in the
      form of excitation-emission matrix of fluorescence intensity as a function of
      excitation and emission wavelengths were applied to study the complexation
      between DOM extracted from landfill leachates and Hg(II) ions. The emission
      spectrum of DOM exhibited a broad peak with a center at 425 nm and a disorder
      change of the peak with increasing Hg(II) concentrations, which suggested that
      the structure of DOM was comparatively simple and the fluorescence character of
      DOM-Hg(II) complexes resulted from interaction of all fluorescence groups. The
      excitation spectrum of DOM showed that the intensities of two peaks at 392 and
      458 nm both decreased with the addition of Hg(II), indicating that different
      sources, hydroxy and amido groups, were all involved in the DOM-Hg(II)
      complexation process. Synchronous-scan excitation spectra of DOM-Hg(II)
      complexation showed that Hg(II) not only produced fluorescence quenching effect,
      but also enhanced the rigid structure of DOM at a low concentration. The three
      dimensional fluorescence spectra of DOM-Hg(II) showed that the peaks A and B
      reduced strongly and the two peaks tended to shift toward longer wavelength with
      the concentrations of Hg(II) increasing. These results indicated that protein
      like matter reacted with Hg(II) and there was a charge-transfer transition either
      between energy level in its ligand and a mercury energy level or between two
      mercury energy levels at the same time. Besides, the decrease in fluorescence
      intensity of peaks C and D in three-dimensional fluorescence spectra suggested
      that carbonyl and carboxyl formed bonds with Hg(II) when DOM was complexed with
      Hg(II).

PMID- 19839340
TI  - [Effects of exogenous salicylic acid on photosynthesis in Arabidopsis leaves
      based on fluorescence spectra and delayed fluorescence technique].
AB  - Salicylic acid plays an important role in the active oxygen metabolism and the
      photosynthesis of the plant. Wild type Arabidopsis thaliana (ecotype Columbia)
      and it's two different mutants were used as experimental material: one is the
      cpr5 mutant which has an abundant endogenesis SA level under stress conditions,
      and the other is the eds-4 mutant which has a lacking endogenesis SA level under
      stress conditions. The leaves of those three different Arabidopsis were treated
      with 100, 300, and 500 micromol x L(-1) concentrations of salicylic acid,
      respectively. The fluorescence emission spectra and the delayed fluorescence were
      detected respectively. The authors found that there was a slight elevation in the
      photosynthetic efficiency of PS II of the WT and eds-4 leaves with 100 and 300
      micromol x L(-1) SA treatment. However, there was a decrease in the
      photosynthetic efficiency and even a stress of the cpr5 leaves with 100 and 300
      micromol x L(-1) SA treatment. It was also showed that there came to be an
      obvious stress of the leaves of all three different kinds of Arabidopsis with 500
      micromol x L(-1) SA treatment and the photosynthetic efficiency of them decreases
      sharply. The generation of active oxygen was also detected with the DCF labeling
      under 500 micromol x L(-1) SA treatment. The authors found that there was an
      obvious accumulation of active oxygen along with the time under SA treatment.

PMID- 19839341
TI  - [Quantitative analysis of phenanthrene and humic acid in solution based on
      fluorescence method].
AB  - Polycyclic aromatic hydrocarbons as a universal concern in the monitoring of
      priority pollutants have low content in the water environment and are interfered
      with the coexistence of humic acid. The spectra of humic acid and polycyclic
      aromatic hydrocarbons overlap seriously, so it was difficult to use the
      conventional methods for rapid quantitative detection. As a model compound of
      polycyclic aromatic hydrocarbons, Phenanthrene (PHE) was chosen in the
      experiment. The fluorescence spectra of PHE and humic acid (HA) were investigated
      by three dimensional fluorescence excitation-emission matrix. The method combined
      excitation-emission matrix fluorescence spectra with parallel factor analysis and
      was applied to determine PHE and HA directly. The excitation wavelength changed
      from 240 to 360 nm at an interval of 5 nm. The emission wavelength varied from
      260 to 575 nm at an interval of 5 nm. The satisfactory results show that this
      experiment can be easily performed without paying out time-consuming and
      complicated procedures.

PMID- 19839342
TI  - [Application of fluorescence microscopic imaging technique with self-ordered ring
      to residues detection of antibiotics].
AB  - Fluorescence microscopic self-ordered ring (SOR) technique with microwave heating
      is proposed for minocycline based on the capillary flow of solvent on the surface
      of hydrophobic glass slide and applied to residues detection of the antibiotics
      in milks of Inner Mongolia. In the reaction medium of hexahydropyridine
      containing polyvinyl alcohol-124 (PVA-124), a SOR of minocycline with the outer
      diameter of 1.54 mm and the ring belt width of 22.6 microm can be formed. When a
      0.30 microL droplet of minocycline mixture was spotted on the solid surface,
      minocycline in the range of 4.2 x 10(-2)-1.8 x 10(-11) mol x ring(-1) (1.4 x 10(
      6)-0.60 x 10(-5) mol x L(-1)) can be detected, the maximum fluorescence intensity
      was found to be proportional to the minocycline concentration, and the limit of
      detection can reach 4.2 x 10(-13) mol x ring(-1) (1.4 x 10(-7) mol x L(-1)) with
      three times of signal to noise ratio. With the present method, the contents of
      minocycline in milk samples of Inner Mongolia and minocycline hydrochloride
      capsule sample were satisfactorily determined with recoveries of 97.2%-103% and
      99.4%-102%, respectively, and RSD lower than 1.2%, correspondingly. Therefore, a
      highly sensitive and selective analysis method for detecting content of trace
      drug contaminations was established. The method provided theory basis to
      quantificational analysis of the residues of the antibiotics in milks which was
      Inner Mongolia' preponderant resource products. It has important realistic
      meaning and broad application prospect.

PMID- 19839343
TI  - [Determination of Norfloxacin by its enhancement effect on the fluorescence
      intensity of functionalized CdS nanoparticles].
AB  - A novel assay of Norfloxacin with a sensitivity at the microgram level is
      proposed based on the measurement of enhanced fluorescence intensity signals by
      the interaction of functionalized nano-CdS with Norfloxacin. The CdS
      nanoparticles were synthesized by thioacetamide (TAA) and cadmium nitrate
      (Cd(NO3)2) in the alkaline solution, and the nanoparticles proved to be stable in
      the aqueous solution. At pH 7.4, the fluorescence signals of functionalized nano
      CdS were greatly enhanced by Norfloxacin in the region of 300-700 nm
      characterized by the peak around 495 nm, and the surface defect-related emission
      located at 565 nm. However, the surface defect-related emission was
      unconspicuous, thus we concluded that the functionalized nano-CdS QDs (Quantum
      Dots) possessed excellent luminescence capability and favourable structure. At
      the same time, the absorption spectra and transmission electron microscopy (TEM)
      also proved this deduction. The external reaction conditions (such as effect of
      buffer system, pH, ionic strength, reaction time and temperature, colloid
      concentration) were discussed. The result showed that better fluorescence signals
      could be obtained in the condition of 0.10 mol x L(-1) Tris-HCl, pH 7.4, 0.1 mol
      x L(-1) NaCl and the reaction time 5 min. The fluorescence emission spectra of
      CdS QDs with increasing Norfloxacin concentration were recorded under the optimal
      condition. From the fluorescence intensity and peak position of nano-CdS
      colloidal as different concentration of Norfloxacin was added, the possible
      mechanism of reaction between mercapto-acetic acid capped CdS and Norfloxacin was
      discussed. Linear relationship can be established between the enhanced
      fluorescence intensity and Norfloxacin concentration in the range of 1.25-11.25
      microg x mL(-1) (3.92-35.27 micromol x L(-1)) or 11.25-100.0 microg x mL(-1)
      (35.27-313.5 micromol x L(-1)). The limit of detection is 1.5 x 10(-3) x microg x
      mL(-1), which can be applied to the determination of blood serum samples. Based
      on this, a new direct quantitative determination method for Norfloxacin in
      synthetic samples without separation of foreign substances is established. At the
      same time, the possible enhancing mechanism is due to the formation of exciplex
      during reaction between nano-CdS and Norfloxacin, providing a guidance for the
      study of pharmacokinetics.

PMID- 19839344
TI  - [Study on the determination of permanganate index by UV-Vis spectrometry].
AB  - Permanganate index is an important parameter to evaluate the organic pollution
      for water sources, and the current national standard method is titration analysis
      which needs large sample and is complicated. A new analytical method of measuring
      permanganate index in surface water using UV-Vis spectrometry has thus been
      studied. In the laboratory work, analytical wave-length of UV-Vis spectrometry
      was chosen. The effect of sulfuric acid dosage, concentration and dosage of KMnO4
      together with heating temperature and time was identified. In order to evaluate
      this new method, the linear relationship of this method was tested and the
      analysis results were compared with those by titration method. The selected
      optimum analysis parameters were: 525 nm wavelength, 25% H2SO4 dosage of 5.00 mL,
      0.012 50 mol x L(-1) KMnO4 dosage of 2.00 mL, 30 min heating time at the
      temperature of 100 degrees C. This UV-Vis spectrometry method was successfully
      applied to measuring the permanganate index of the samples collected from the
      Jialing River and the Yangtze River. Compared with the current national standard
      method, this method is time and cost efficient, sensitive and precise, with low
      reagent usage; and is also easy to be manipulated and can be employed for online
      monitor, thus making it an environmental friendly analysing method.

PMID- 19839345
TI  - [Study of determination of phenol derivatives based on ultraviolet absorption
      spectra].
AB  - The ultraviolet absorption spectra of phenol and its derivatives were studied
      under water solution condition. The results show that the introduction of 2-, 3-
      and 4- substituent of group leads to a bathochromic shift of position of the
      maximum absorption wavelength lambda(max), and also increases the molar
      extinction coefficient epsilon(max). However, the extent of influence of
      substituent of group on lambda(max) and epsilon(max) differs with the
      introduction position. Compared with 2- and 3- substituent, the 4-substituent
      induces a bathochromic shift of lambda(max) and the increase of epsilon(max) more
      greatly, due to the more formation of conjugated structure between 4-substituent
      of group and benzene ring. The characteristics of 4-nitrophenol's lambda(max) and
      E(max) supply evidence that nitro is a better auxochrome for phenol derivatives.
      So UV methods were established for the determination of the contents of phenol
      derivatives. Using these methods, the adsorptive percentage of four phenol
      derivatives with epsilon(max) >10 000 was determined, which indicates that phenol
      derivatives have larger adsorptive percentage in soils with heavy texture, and
      the solution of inorganic compound with larger concentrations could increase its
      adsorptive percentage.

PMID- 19839346
TI  - [Effect of strengthening solar ultraviolet B band irradiation on oat (Avena
      sativa L. ) yield and its components in Qing Tibetan Plateau].
AB  - Stratospheric ozone depletion occurs mainly over polar regions during the spring
      when the solar Ultraviolet B-band (280-315 nm, UV-B) radiation is most intense in
      a year, but over the Qing Tibetan Plateau region, the highest intensity is from
      June to September when the amount of UV-B radiation reaching the regions is more
      than that in the adjacent areas lying in the same latitude by 10%. From June to
      September is just the time of plant's germination, development, and reproduction
      in the alpine region. UV-B radiation may alter the reproduction of the forage
      plant, oat (Avena sativa.), which plays the vital role in developing indigenous
      herdsman's animal husbandry industry. The responses of oat yield and its
      components to the enhanced ultraviolet B band irradiation under the field
      condition were surveyed. The effect shows that the grain yield is decreased
      significantly by strengthened UV-B irradiation, and at the same time the main
      consequence is the decrease in both the number of ears per square meter and the
      number of grains per ear, but the weight of 1 000 grains appears not
      significantly different. Compared with the same respective location in a
      spikelet, the grain weight is decreased significantly under the treated
      condition, mostly because of the decreases in the number of the third and forth
      floret grain and the grain weight at those respective positions, and the
      percentage of the first and second floret grain and their weight are evidently
      approved on the contrary.

PMID- 19839347
TI  - [Study of microelements in plant's ash and environmental soil by microwave
      digestion ICP-AES].
AB  - A model MDS-2002A microwave digestion sample preparation system with auto control
      pressure in obturation was developed for the determination of microelements in
      clearing-up plant's ash and environment soil sample by ICP-AES. The authors
      discussed sample preparation result influenced by mixed acid system, scale of
      mixed acid dispensation, proportion between solid and liquid and time of
      microwave clearing. Excellent project was A2B1C2, work procedure 2 in microwave
      process. When the dispensation scale was 6 : 2 : 1 : 1 and mixed acid system was
      HNO3-HCl-HF-HClO4, the result was the best in 10 min of microwave clearing at
      highest power. The reagent was dried at constant temperature electric heating
      board, with its salinity being dissolved by aqua fortis. The method was validated
      through the soil (GBW07401) and plant (GBW07603) for national standard matter.
      The relative error of its result is between 0.00% and 7.14%, and the relative
      standard deviation is between 0.87% and 5.25%. The method is quick, handy, saving
      reagent and completely digesting in dealing with plant's ash and soil sample, and
      the accuracy and precision of results are satisfying.

PMID- 19839348
TI  - [Analysis of some nutrients and minerals in organic and traditional cherry tomato
      by ICP-OES method].
AB  - 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 and traditional
      cherry tomato fruit were analyzed by ICP-OES, and the contents of some
      nutritional ingredients such as water, total soluble solid, soluble sugar and
      asorbic acid were also investigated. The results showed that the contents of K,
      Ca and Zn in organic cherry tomato were 1.62, 71.7 and 1.34 mg x g(-1), which
      were 4.52%, 129.81% and 65.43% respectively higher than those in traditional
      tomato. There were no significant differences in the contents of Mg and Fe, which
      showed 73.8 and 2.05 mg x g(-1) in organic cherry tomato. But the content of Mn
      in organic tomato was 0.475 mg x g(-1), 11.22% lower than that in traditional one
      (alpha = 0.05). The contents of Cu, Cd and Pb showed no significant differences
      in the two kinds of tomato, which were 0.457 mg x g(-1), 4.86 ng x g(-1) and
      0.127 mg x g(-1) respectively in organic cherry tomato, and all the contents were
      lower than the national requirement. There were no significant differences in the
      contents of water, soluble sugar, and asorbic acid, but the total soluble solid
      and the content of soluble protein were significantly higher in organic cherry
      tomato. The differences in the nutritional ingredients and mineral elements and
      safety status in the two kinds of tomato provide academic data for the evaluation
      of organic vegetables and traditional ones.

PMID- 19839349
TI  - [Determination of trace elements in Paris polyphylla var. Yunnanensis by ICP
      AES].
AB  - Determination of metal elements in Paris polyphylla var. yunnanensis was studied
      by ICP-AES after HNO3-H2O2 digestion. The average recovery of the method for K,
      Mg and trace elements such as Cu, Fe, Cr, Zn, Mn and Pb in the Paris polyphylla
      var. yunnanensis was found to be 93.7%-108.2%, while RSD (n = 5) was 0.7%-4.6%
      for the metal elements. The method was applied to the analysis of some practical
      samples, and the results obtained were satisfactory. There is rich Fe in the
      samples. It is of important significance to assess the value of the Chinese
      medicine by the determination of trace elements in it with ICP-AES.

PMID- 19839350
TI  - [Simultaneous determination of impurities in K2CrO4 by ICP-AES].
AB  - The trace elements, Ca, Mg, Ba, Co, Cd, Cu, Mn, Pb, Sr, Zn, Al, Fe, Ni, Ti, Si
      and V, in K2CrO4 were simultaneously determined by inductively coupled plasma
      atomic emission spectrometry (ICP-AES). Optimum spectral lines were selected for
      each analyzed element. The matrix effect was studied and eliminated through
      matrix matching. The results show that the linear correlations of standard curves
      are good (R2 = 0.998 6-1.000) under the determined conditions. The recoveries of
      standard addition are in the range of 83.7%-113.0%, and the relative standard
      deviations are lower than 9.48% (n = 9). Detection limits of these impurities are
      in the range of 0.075-2. 625 mg x kg(-1). The method is rapid, simple, accurate
      and credible, so it can be used for the determination of impurities in K2 CrO4
      product. The results also show that there is relatively high content of Ca, Mg,
      Al and Si in K2 CrO4 product, so the K2 CrO4 product can't be directly used for
      the ion membrane electrochemical synthesis of chromic anhydride and the product
      must be taken for further purification.

PMID- 19839351
TI  - [Study on ultrasonic nebulizer sample feeding system for ICP-AES].
AB  - The sample feeding system of inductively coupled plasma atomic emission
      spectrometry (ICP-AES) is pneumatic nebulization system, but its efficiency is
      not good. The ultrasonic nebulization technology possesses advantages of high
      nebulization efficient and fine droplets, and it is free of blocking phenomenon.
      It has good application perspective in nebulization technology. In the present
      paper the authors study the working conditions of ultrasonic nebulizer such as
      carrier gas flow, injection time, injection rate and mode of washing that are
      likely to affect the detection results, and study the detecting conditions of
      several elements such as As and Se etc. that have poorly detection limits in
      normal ICP-AES methods. At the same time, the application of them in biochemical
      samples was studied. Testing results show that carrier gas flow, injection rate
      and injection time can greatly affect the intensity of spectral lines, and the
      ultrasonic nebulizer sample feeding system can increase the spectral line
      intensity and decrease the detection limit elements such as As, Pb, Se, Bi, Ge,
      Mo, Cd and Cu by about 10-25 times. Moreover, this ultrasonic nebulizer sample
      feeding system can reduce the time of memory effect by washing the sample cell.

PMID- 19839352
TI  - [Determination of inorganic elements in oleum camelliae by ICP-AES].
AB  - In the present study, the contents of eighteen inorganic elements such as Ca, K,
      Mg, Cu, Cr, Zn and Sr in oleum camelliae during different stages of refining
      process were determined using ICP-AES technique. The recoveries obtained by the
      standard addition method ranged between 82.7% and 112.5%, and RSDs were lower
      than 6.66%. The detection limits of the method for the eighteen elements were in
      the range of 0.4-10 microg x L(-1). The experimental results proved that oleum
      camelliae is rich in inorganic elements. The results also showed that depending
      on the intensity of refining, the contents of elements will decrease accordingly.
      After the degumming process, the contents of elements P, Ca and Mg in oleum
      camelliae declined remarkably. Besides, the contents of some trace elements such
      as Fe, Cu, Mn and Ni that cause oxidation to occur decreased significantly after
      refining. In addition, Pb was not detected after the degumming and
      deacidification process while Co and Cd were not detected both in the crude oil
      and the refined oil. In conclusion, through refining many excessive metal
      elements in oleum camelliae were removed effectively and the levels of these
      elements were able to meet the national standards set by the government.
      Meanwhile, the experimental results indicated that the ICP-AES technique, which
      can be used to determine the inorganic elements in oleum camelliae, is easy to
      operate, rapid, accurate, and highly sensitive, and can also determine many
      elements simultaneously.

PMID- 19839353
TI  - [Determination of trace Hg element in gas by CVAAS with single optical path].
AB  - Since the anthropogenic emissions of mercury into environment were mostly
      entering the atmosphere through flue gas, continuous monitoring of mercury in the
      flue gas was significant for mercury emission control. A bench scale test rig was
      set up for the measurement of mercury through both wet chemical method and CVAAS
      (cold vapor atomic absorption spectrometry) with single optical path. The
      concentration of Hg in absorbent solution was determined by Hydra AA mercury
      analyzer. The concentration of Hg in gas was calculated in terms of wet chemical
      testing results, which showed a stable rate of permeation device. Hg atom
      absorption signal intensity was detected and analyzed in comparison with the test
      results of wet chemical methods according to Beer-Lambert law. Experimental data
      well agreed with the theory analysis, which indicated that the single optical
      path was suitable for the determination of trace Hg element in pure gas. Further
      research work should aim at the improvement of system adaptability and anti
      jamming ability. To reduce the intensity fluctuation of mercury lamp, another
      spectral line could be detected simultaneously. Interference from surroundings,
      e.g. dust in gas or spot on the quartz surface, could be eliminated by
      optoelectronic coupling.

PMID- 19839354
TI  - [The study of trace elements in Cap paris spinosa L].
AB  - To provide a scientific basis for the research and development of Cap paris
      spinosa L and determine the content of trace elements abundant in seeds.
      Determination of eight predictive trace elements, Cu, Zn, Fe, Mn, Ca, K, Mg and
      Cr, was carried out by ICP-AES. Among the determined eight predictive trace
      elements, the contents of Fe, Zn, Cu and Cr are the highest. Cap paris spinosa L
      is worth researching deeply not only chemically but also pharmacologically as a
      Chinese Uygur herb.

PMID- 19839355
TI  - [Determination of major, minor elements in the samples of SrCO3 product by X-ray
      fluorescence spectrometry].
AB  - In the present paper a method for the determination of strontium, barium,
      calcium, magnesium, silicon, iron, aluminum and sulfur in the product of
      strontium carbonate by X-ray fluorescence spectrometry with pressed powder sample
      preparation was developed, and the standard samples were synthesized by high
      purity reagent. As the contents of strontium in the product of strontium
      carbonate were very high, the phenomenon of spectrum-peak-saturated occurred and
      the count rate was overflowed according to the measuring condition which was
      automatically given by the software system of X-ray fluorescence spectrometry. As
      a result, the deviation of the measurement is greater. According to analyzing the
      measuring condition of strontium, a method was given for reducing the count rate
      by reducing the measuring power of strontium, thus achieving the goal of
      measurement. When sulfate was measured with pressed powder sample, the results
      were enhanced with the increase in measuring number. In light of this situation,
      a method was proposed to solve the problem. As the self-forming characteristic of
      the product of strontium carbonate was not so well, it was very difficult to
      press the sample successfully. So, the condition of squash method involving the
      kinds of the adhesives, the mixing technique with powder sample and the pressing
      time technique was discussed. During making the sample, it was found that the
      effects of pellet formation were better if the time could be delayed by 120
      seconds. Matrix effect was corrected by alpha coefficient method, the accuracy of
      the method was evaluated by analysis of synthetic sample. Detection limits of
      0.623-107.6 mg x g(-1) were obtained. The results were in good agreement with
      certified values with precision of < 2.5% RSD.

PMID- 19839356
TI  - [X-ray excited luminescence property of ZnS : Au, Cu fine particles synthesized
      by hydrothermal method].
AB  - Highly luminescent ZnS : Au, Cu X-ray phosphor fine particles synthesized by
      hydrothermal method is reported for the first time and its photoluminescence (PL)
      and X-ray excited luminescence (XEL) properties were studied in detail. With
      direct hydrothermal treatment at 200 degrees C for 12 h, the average gain size of
      samples is about 15 nm; the synthesized sphere-like nanocrystals with well
      dispersity and narrow gain size distribution show cubic structure. After baking
      in argon at 1 000 degrees C for 1h the sample agglomerate size is about 1-2
      microm and the roughly spherical fine particles show pure hexagonal structure.
      The PL and XEL spectra of all the samples show a broad emission band and an
      intense emission band in the range of 400-600 nm. The maximum XEL intensity of
      sample directly synthesized by hydrothermal treatment was observed when Cu/Zn and
      Cu/Al were 3 x 10(-5) and 2, respectively. In this condition, the strongest PL
      emission was observed for the direct synthesized sample being further baked in
      argon at 900 degrees C for 1 h and the PL peak was centered at about 529 nm. The
      strongest XEL emission was observed for the direct synthesized sample being
      further baked in argon at 1 000 degrees C for 1h and the XEL peak was centered at
      about 445 and 513 nm, respectively. In the meantime, the XEL intensity increased
      about ten times compared with that directly synthesized without baking. The
      difference between PL and XEL spectra is due to its different excitation
      mechanism. The luminescence mechanism and different excitation mechanism of PL
      and XEL were discussed. The red shift of XEL spectrum with directly synthesized
      sample was observed with increasing the Cu/Zn. The reason can also be explained
      by the luminescence mechanism and excitation mechanism of XEL.

PMID- 19839357
TI  - [A quantitative trabecular structural analysis using X-ray micro CT in
      ovariectomized rats].
AB  - The objective of the present paper was to evaluate the X-ray three-dimensional
      micro-computed tomography (X-microCT) method applied in assessing the trabecular
      structure in ovariectomized rats. Three-month-old female Sprague-Dawley rats (n =
      30) were ovariectomized (OVX) or sham-operated (SHAM). OVX rats were treated with
      vehicle, or 17beta-estradiol (E2, positive control) for 3 months. For the
      conventional histomorphometric analysis, undecalcified sections were prepared and
      stained with the Li Chunhong technique to obtain high-contrast two-dimensional
      images. Prior to the histologic sectioning the samples were measured by X
      microCT, providing a 14 microm resolution. The morphometric parameters computed
      by both methods in two or three dimensions, respectively, were bone volume over
      total volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N)
      and trabecular separation (Tb. Sp). Results showed that there were significant
      differences in the trabecular structure among three groups. In the OVX control
      group, the platelike structure was mostly resolved into a rodlike structure, with
      lots of the connecting rods missing. Whereas in OVX+E2 groups, this loss of
      trabecular bone mass and connectivity was prevented, with the results being
      nearly the same as those in the SHAM group. It was shown that highly significant
      correlations between conventional histology and X-microCT for BV/TV, Tb. Th, Tb.
      N and Tb. Sp were 0.984, 0.960, 0.995, and 0.988 in tibia, and 0.938, 0.968,
      0.877 and 0.951 in lumbar. The high correlations between conventional
      histomorphometric and micro-tomographic analysis are very promising for the use
      of micro-tomographic imaging. X-microCT is a nondestructive, fast, and very
      precise procedure that allows the measurement of cancellous tissue in unprocessed
      biopsies or small bones, as well as a fully automatic determination of three
      dimensional morphometric indices.

PMID- 19839358
TI  - [Design method of convex master gratings for replicating flat-field concave
      gratings].
AB  - Flat-field concave diffraction grating is the key device of a portable grating
      spectrometer with the advantage of integrating dispersion, focusing and flat
      field in a single device. It directly determines the quality of a spectrometer.
      The most important two performances determining the quality of the spectrometer
      are spectral image quality and diffraction efficiency. The diffraction efficiency
      of a grating depends mainly on its groove shape. But it has long been a problem
      to get a uniform predetermined groove shape across the whole concave grating
      area, because the incident angle of the ion beam is restricted by the curvature
      of the concave substrate, and this severely limits the diffraction efficiency and
      restricts the application of concave gratings. The authors present a two-step
      method for designing convex gratings, which are made holographically with two
      exposure point sources placed behind a plano-convex transparent glass substrate,
      to solve this problem. The convex gratings are intended to be used as the master
      gratings for making aberration-corrected flat-field concave gratings. To achieve
      high spectral image quality for the replicated concave gratings, the refraction
      effect at the planar back surface and the extra optical path lengths through the
      substrate thickness experienced by the two divergent recording beams are
      considered during optimization. This two-step method combines the optical-path
      length function method and the ZEMAX software to complete the optimization with a
      high success rate and high efficiency. In the first step, the optical-path-length
      function method is used without considering the refraction effect to get an
      approximate optimization result. In the second step, the approximate result of
      the first step is used as the initial value for ZEMAX to complete the
      optimization including the refraction effect. An example of design problem was
      considered. The simulation results of ZEMAX proved that the spectral image
      quality of a replicated concave grating is comparable with that of a directly
      recorded concave grating.

PMID- 19839359
TI  - [Research on the near-infrared spectrometer system].
AB  - Near-infrared spectrometer is the integration of spectrum test technology,
      stoichiometry technology and computer technology. In the present paper, based on
      effective food ingredients and non-invasive quantitative detection, the
      development process of the micro-near-infrared spectrometer system was
      introduced. Spectrometer is the basis of the system. This paper focuses on the
      development of the micro-near-infrared spectrometer applicable to on-line real
      time testing. A micro-near-infrared spectrometer prototype was developed
      successfully, its main technical parameter was tested, and the result shows: its
      operating wavelength is: 850-1 690 nm, optical resolution is: less than 10 nm,
      and its performance has achieved the level of the congener foreign products.
      Stoichiometric technology and computer technology is the core of the system. LS
      LWR modeling methods were proposed. Finally, the quantitative test for glucose
      water solution using the micro-near-infrared spectrometer shows that the
      correlation coefficient of prediction model is 0.995, and the corresponding RMSEP
      is 0.06.

PMID- 19839360
TI  - [Development of X-ray excited fluorescence spectrometer].
AB  - An X-ray excited fluorescence spectrometer was developed with an X-ray tube and a
      spectrometer. The X-ray tube, spectrometer, autocontrol method and data
      processing selected were roundly evaluated. The wavelength and detecting
      efficiency of the apparatus were calibrated with the mercury and tungsten bromine
      standard lamps, and the X-ray excited emission spectra of BaF2, Cs I (Tl)
      crystals were measured. The results indicate that the apparatus has advantages of
      good wavelength resolution, high stability, easy to operation and good
      radioprotection. It is a wery effective tool for exploration of new scintillation
      materials.

PMID- 19839361
TI  - [Experimental research on remote sensing spectrometer's instrument response
      function].
AB  - Remote sensing spectrometers were widely used in the fields such as spectral
      measure and trace gas supervision in atmosphere. The instrument response
      functions should be measured to eliminate the effect of the spectrometer. The
      instrument response functions of MCT detector and InSb detector in BLUKER TENSOR
      37 passive FTIR spectrometer were measured in the present paper. The instrument
      response functions and background functions were offered with different
      temperature interval. The instrument response functions of MCT detector increased
      with temperature, but it was the reverse for InSb detector. The background
      functions of InSb detector increased with temperature, and the reverse for MCT
      detector.

PMID- 19839362
TI  - [Design of advanced glycation endproducts fluorescence spectrum detecting
      system].
AB  - The method of making use of the technique of fluorescence spectrum to detect
      advanced glycation endproducts is discussed in the present pape. The emphasis is
      on the principle and structure of the fluorescence spectrum detecting system. In
      the end, the authors made use of the system to detect the excitation spectrum at
      the wavelengths of 365nm, 370nm, 375nm, 380nm and 385nm, respectively, and the
      authors found that 375nm is the best excitation wavelength. At the same time, the
      emission spectrum was also detected on the skin of nondiabetic people and
      patients with diabetes respectively. The result of the experiment indicates that
      there is a difference distinctly at about 450nm between them, and has proved the
      feasibility of the system. The detecting system does not need collecting blood
      sample, is a noninvasive detection technology, and avoids pain and infection to
      the patients. The process of detection is very rapid and convenient, and the
      repetitiveness is well. The patient can benefit from it to forecast and diagnose
      the state of illness such as diabetes, decrepitude and oxidative stress etc
      conveniently.

PMID- 19839363
TI  - Lymphoid and histiocytic proliferations in HIV-positive patients: problems in
      diagnosis.

PMID- 19839364
TI  - Differentiating HIV-associated non-Hodgkin's lymphomas with similar
      plasmacellular differentiation.

PMID- 19839365
TI  - Peripheral T-cell lymphomas in HIV-infected individuals: a comprehensive review.

PMID- 19839366
TI  - Pathology of Kaposi's sarcoma.

PMID- 19839367
TI  - [Social psychiatry].

PMID- 19839368
TI  - [Current topics in pharmacokinetics and pharmacogenetics of antidepressant
      drugs].
AB  - For antidepressants as well as for other drugs, personalized prescription has
      become a major challenge, provided the large interindividual variability
      encountered both at the pharmacokinetic and the efficacy and tolerance levels.
      Better identification of the numerous relevant factors and quantification of
      their effects are prerequisites to progress in that direction. On the basis of
      recent literature, genetic factors are first reviewed, including polymorphisms of
      genes coding for drug-metabolizing enzymes, transporters and pharmacodynamic
      target molecules. Current recommendations with respect to therapeutic drug
      monitoring of antidepressants and use of pharmacogenetic testing are then
      summarized.

PMID- 19839369
TI  - [Brief-DISCERN, a possible way to improve patient's search on the health-related
      web].
AB  - Internet is increasingly used as a source of information on health issues and is
      probably a major source of patients' empowerment. This process is however limited
      by the frequently poor quality of web-based health information designed for
      consumers. A better diffusion of information about criteria defining the quality
      of the content of websites, and about useful methods designed for searching such
      needed information, could be particularly useful to patients and their relatives.
      A brief, six-items DISCERN version, characterized by a high specificity for
      detecting websites with good or very good content quality was recently developed.
      This tool could facilitate the identification of high-quality information on the
      web by patients and may improve the empowerment process initiated by the
      development of the health-related web.

PMID- 19839370
TI  - [Integration processes and clinical governance in the psychiatric network].
AB  - The Swiss Medical Insurance Act (LAMaL) requires the planning of psychiatric
      care. This necessitates a coordination between the Department of Public Health
      and the institutional governance. Given the difficulties to draw comparisons
      between a wide range of systems in a federal country, the Swiss Conference of the
      State Directors of Health (CDS) proposed as a first step that each canton present
      some of the key programs they had developed. In the canton Vaud, the
      implementation of mobile community treatment teams and of an early intervention
      program for psychosis was chosen. The main challenges faced were to go past
      traditional divides within the organisation of the Swiss Health system and to
      conciliate the requirements of public health with the needs of treating teams, in
      order to promote early intervention in mental health disorders.

PMID- 19839371
TI  - [Action research and clinical governance: the example of the project "psychiatry
      and migrants" at the Vaudois University Medical Center].
AB  - Action research is a useful instrument for the organization health care and the
      clinical governance of psychiatric institutions. What this type of research
      offers can be illustrated by the cohort study of migrant patients without health
      insurance who consulted the Department of Psychiatry of the Vaudois university
      medical center (CHUV) in 2008. While giving greater visibilty to the
      psychological suffering and social distress of these patients, the study also
      enabled the authors to determine which clinical procedures were actually offered
      to these patients and the amount these procedures cost the department. The small
      number of cases that were identified as well as their uneven distribution amongst
      the different services of the department suggest that considerable efforts must
      still be made to improve access for this population to public psychiatric
      services.

PMID- 19839372
TI  - [Mental health and psychiatry: role and issues of the Geneva mental health
      associations' network].
AB  - The psychosocial Geneva-based associations provide ongoing support to people
      suffering from mental disorders and their families. This network gives
      psychological care and works towards social inclusion. This approach is an
      alternative as well as a complement to medical care. The services offered by the
      associations are varied: mutual self-help, providing a place to live and a space
      dedicated to specific activities, family support, counselling, therapy, etc. They
      have two central issues: improving quality of life and promoting the rights of
      patients. Collaboratively, they are in constant dialogue with the psychiatric
      institutions in the canton, leading to joint activities and furthering the
      thinking on patient health and rehabilitation.

PMID- 19839373
TI  - [Psychiatry under constraint - the issue of planning in mental health care].
AB  - Given the important modifications of the "Loi sur l'Assurance maladie (LAMal)",
      this article gives a contribution to the hospital planification by identifying
      the main factors that have determined the current organisation of the psychiatric
      care network. We notice a gap between the orientations of these networks and the
      funding scheme forecast in the framework of the LAMal. In order to preserve the
      progressions of these last years and to avoid the negative effects of a too
      restrictive funding act for the assignment of the public psychiatry, the
      planification must result in a consensus between the state, the insurances and
      the multiple actors of the mental health. Otherwise, this will be done to the
      detriment of the activities of secondary prevention, of coordination in the
      network, of support to the natural helpers, and of intervention to the vulnerable
      populations.

PMID- 19839374
TI  - [The challenges of innovation to the Swiss health care system].

PMID- 19839375
TI  - [Our pandemic: modern or no?].

PMID- 19839376
TI  - [The enjoyment of wine versus alcoholism].

PMID- 19839377
TI  - [Praise the handkerchief and the proper way of handwashing (1)].

PMID- 19839378
TI  - [Re-engineering health care].

PMID- 19839379
TI  - AIDS vaccine.

PMID- 19839380
TI  - A long-lost relative.

PMID- 19839381
TI  - Teen tanning.

PMID- 19839382
TI  - Two takes on Turkish targets.

PMID- 19839383
TI  - Case study and subsequent audit.

PMID- 19839384
TI  - A comparison of methods used for the prevention of venous thromboembolic disease
      among orthopaedic surgeons at Wolverhampton, United Kingdom and Auckland, New
      Zealand.

PMID- 19839385
TI  - The US Defense Intelligence Agency's National Center for Medical Intelligence.

PMID- 19839386
TI  - Writing your postgraduate dissertation: a basic framework.
AB  - This paper provides a basic framework for those embarking upon a postgraduate
      dissertation. The dissertation experience can offer many opportunities for self
      and academic development once ethical approval has been obtained. A good
      dissertation is the result of a sound methodological framework, where some
      thought has been given to the strengths and weaknesses of qualitative and
      quantitative methods of inquiry. The research question needs to be given careful
      consideration so that the aims and objectives of the postgraduate research
      project are fulfilled.

PMID- 19839387
TI  - New Entry Medical Officers course 2008--a personal review.

PMID- 19839388
TI  - Re: Asbestos--a legacy and a persisitent problem.

PMID- 19839389
TI  - Communication, vaccinations are among key H1N1 quality concerns.
AB  - Communicate with staff on every aspect of your planning. One-on-one education
      sessions may be most effective. Strive to have as many employees as possible
      vaccinated.

PMID- 19839390
TI  - Is an outcomes-based approach the best?
AB  - Morbidity, mortality rates improve in outcomes-based collaborative. Risk-adjusted
      clinical data provide clearer picture of performance. "Everything in moderation"
      is best way to use alternate approaches.

PMID- 19839391
TI  - Health plan, physicians collaborate, improve care.
AB  - The pilot melds quality improvement, coordinated care management, and patient
      educational services into primary care practices. The program is aimed at
      lowering overall costs for employers and absenteeism. It is an opt-out program.

PMID- 19839393
TI  - Dignity in dying.

PMID- 19839392
TI  - TJC urges CEOs to lead the fight against MDROs.
AB  - Toolkit created as "call to action to health care executives." Financial impact
      of MDROs should compel CEOs to get involved. Executives are "uniquely positioned"
      to contribute to the end of the era of antibiotic resistance.

PMID- 19839394
TI  - Positively downbeat.

PMID- 19839395
TI  - Recession halts retiring docs.

PMID- 19839396
TI  - Full speed ahead. Large projects proceed despite challenging economy.

PMID- 19839397
TI  - [Gastrointestinal signs and symptoms of allergic diseases in children].
AB  - Gastrointestinal food allergies are a spectrum of disorders that result from
      adverse immune responses to dietary antigens. The disorders include immediate
      gastrointestinal hypersensitivity, allergic eosinophilic esophagitis, gastritis,
      gastroenterocolitis, proctitis, dietary protein enterocolitis, enteropathy and
      celiac disease. Additional disorders sometimes attributed to food allergy include
      colic, gastroesophageal reflux and constipation. The pediatrician faces several
      challenges in dealing with these disorders because diagnosis requires
      differentiating allergic disorders from many other causes of similar symptoms and
      therapy requires identification of causal foods, application of therapeutic diets
      and/or medications and monitoring for resolution of these disorders.

PMID- 19839398
TI  - Atopy in preschool Italian children with recurrent respiratory infections.
AB  - OBJECTIVES: Recurrent respiratory infections (RRI) are a common problem mainly in
      pre-school age, due to the presence of unfavourable environmental conditions,
      including early socialization, as well as the immaturity and inexperience of the
      immune system. The relation between atopy and RRI has been evaluated in several
      studies, but the results were not conclusive. This study sought to determine the
      impact of atopy, the immunological and clinical profile in 297 Italian children
      with RRI, younger than 6 years. METHODS: All children were assessed for blood
      leukocyte count, serum immunoglobulin level, IgG subclasses, lymphocytic
      subpopulations, total and specific IgE levels for common food and inhalant
      allergens. RESULTS: A total of 218 children (73.4%) provided a positive family
      history of atopic disorders. Atopy was found in 150 out of 297 children (50.5%).
      Early onset (<1 year) of RRI symptoms occurred more frequently in atopic children
      that in non atopic ones (58.9% vs 44%, p=0.02). A higher percentage of the male
      children (61.6%) got sick, as compared with the percentage of female children
      (38.4%), and the male children were more frequently atopic (67.3% vs 55.8%,
      p=0.03). Thirty-nine out of 297 children (13.2%) were diagnosed as having
      immunological disorders (IgA deficiency, IgG2 deficiency and transient
      hypogammaglobulinemia). CONCLUSIONS: Our results provide evidence that, in our
      population, atopy is a frequent condition and it's likely to be a favouring
      factor for RRI, while the presence of an underlying immunological disease is
      relatively uncommon and immune defects are mostly mild.

PMID- 19839399
TI  - [Children feeding practices in Pakistani families immigrant to Italy].
AB  - BACKGROUND: Immigration to Italy from Asian countries is sharply increasing, but
      little we know about the integration of children born in Italy from migrant
      families. OBJECTIVE: To evaluate which changes in feeding practices has occurred
      in respect of their original culture. METHODS: A cross-sectional study
      investigated the eating habits of 53 children (aged 2-14 years), born in Italy
      from parents who recently moved from Pakistan. Data were collected through a
      questionnaire and interviews. RESULTS: Religious beliefs and poor economical
      conditions interact with the feeding habits of the families. Prolonged, but not
      exclusive breastfeeding is common. According the Pakistani uses, many beverages
      are introduced early in addition to maternal milk. Whereas protein intake is
      usually low in the first two years of life, it tends to becomes excessive during
      school-age. Besides the traditional diet, children widely use savoury and sweet
      convenience food.

PMID- 19839400
TI  - Childhood Crohn's disease presenting as chronic constipation.
AB  - Inflammatory bowel disease (IBD) include Crohn's disease (CD) and ulcerative
      colitis (UC). In children signs and symptoms of IBD are often non-specific,
      diagnosis is more difficult than in adults and systemic manifestation as growth
      failure and delayed puberty are common. While abdominal pain, rectal bleeding and
      diarrhoea are usual symptoms, constipation represents an unusual presentation of
      CD or UC. We report a 9-years-old girl with severe constipation, worsening
      abdominal pain, intermittent fever, diagnosed as CD. To our knowledge, this is a
      rare case of CD presenting as chronic constipation in children; we can find, in
      reviewed recent literature, only few report of similar condition.

PMID- 19839401
TI  - Transient hemi-diaphragmatic palsy following pleural empyema: a pediatric case
      report.
AB  - Phrenic nerve palsy generally is a jatrogenic damage of invasive neck and/or
      chest procedures in the pediatric age, but it does not represent a common
      complication of pleural empyema. One case of transient monolateral diaphragmatic
      paralysis following a decorticated pleural empyema is here reported. Common
      causes of the present disorder and its possible physiopathologic mechanisms are
      discussed, too.

PMID- 19839402
TI  - [Acute hepatitis as a side effect of albendazole: a pediatric case].
AB  - We describe a case of acute hepatitis with jaundice in a patient of seven years
      of age in oral treatment with albendazole; a mild increase of liver function
      tests is a well-known side effect after prolonged administration but acute
      hepatitis has never been described in childhood.

PMID- 19839403
TI  - Role of germanium L-cysteine alpha-tocopherol complex as stimulator of some
      antioxidant defense systems in gamma-irradiated rats.
AB  - This study was conducted to evaluate the potency of the newly prepared germanium
      L-cysteine-alpha-tocopherol complex [germanium dichloro tetrakis (L-cysteinyl
      alpha-tocopherol amide) dichloride] as a protective agent against gamma
      irradiation-induced free radicals production and liver toxicity. Male Swiss
      albino rats were injected intraperitoneally with the germanium complex in a
      concentration of 75 mg kg(-1) body mass per dose, for 6 successive doses, last
      dose administered twenty minutes pre-exposure to a single dose of whole body y
      irradiation of 6.5 Gy. Lipid peroxidation (LPx), nitric oxide (NO), glutathione
      (GSH) levels, and activity of the antioxidant enzymes glutathione peroxidase
      (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in blood and
      liver. Blood total protein, cholesterol, triglyceride and alpha-tocopherol
      content were estimated as well. The results revealed that administration of
      germanium complex pre-irradiation resulted in significant (p < 0.001) improvement
      compared to the irradiated group in the level of hepatic and blood LPx. Hepatic
      GSH revealed a significant increase (p < 0.001), while its level showed no
      significant variation in blood. Also, the level of NO in blood and liver
      increased significantly (p < 0.001). On the other hand, pretreatment with the
      germanium complex normalized the activities of SOD, GPx and CAT in blood and
      liver when compared to the irradiated group. The study also documents a marked
      decrease in a blood triglyceride and cholesterol (p < 0.001) and a significant
      increase (p < 0.001) of alpha-tocopherol and total protein contents in blood.
      These biochemical changes were associated with marked improvement of histological
      status. Therefore, the germanium L-cysteine alpha-tocopherol complex may be a
      good candidate for ameliorating the changes induced by irradiation, which
      indicates the beneficial radio-protective role of this antioxidant agent.

PMID- 19839404
TI  - Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: search for better COX
      2 inhibitors.
AB  - A series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazole N-oxides
      were prepared and evaluated for COX-2 and COX-1 binding affinity in vitro and for
      antiinflammatory activity by the rat paw edema method. p-Methoxy (p-OMe)
      substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher
      than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)
      1,2,5-oxadiazole N-oxide (42) showed COX-2 enzyme inhibition of 54% at 22
      micromol L(-1) and COX-1 enzyme inhibition of 44% at 88 micromol L(-1)
      concentrations, but showed very low in vivo anti-inflammatory activity. Its
      deoxygenated derivative (21) showed lower COX-2 enzyme inhibition (26% at 22 pmol
      L(-1)) and higher COX-1 enzyme inhibition (53% at 88 micromol L(-1)) but, marked
      in vivo anti-inflammatory activity (71% at 25 mg kg(-1)) vs. celecoxib (48% at
      12.5 mg kg(-1)). Molecular modeling (docking) studies showed that the methoxy
      group is positioned in the vicinity of COX-2 secondary pocket and it also
      participates in hydrogen bonding interactions in the COX-2 active site. These
      preliminary studies suggest that p-methoxy (p-OMe) group in one of benzene rings
      may give potentially active leads in this series of oxadiazole/N-oxides.

PMID- 19839405
TI  - Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid
      peroxidation properties of ibuprofen derivatives.
AB  - In order to reduce the ulcerogenic effect of ibuprofen, its carboxylic group has
      been converted into 5-membered heterocyclic rings. Various 1,3,4-oxadiazoles (3
      8, 16-21), 1,2,4-triazoles (22-27), 1,3,4-thiadiazoles (28-30), and 1,2,4
      triazine (9) derivatives of ibuprofen were prepared by cyclization of 2-(4-i
      butylphenyl) propionic acid hydrazide (2) and N1-[2-(4-i-butylphenyl)-propionyl]
      N4-alkyl/aryl-thiosemicarbazides (10-15) under various reaction conditions. The
      cyclized derivatives were screened for their anti-inflammatory activity by the
      carrageenan induced rat paw edema method and showed 50 to 86% inhibition, whereas
      the standard drug ibuprofen showed 92% inhibition at the same oral dose. Five
      compounds, 7, 16, 18, 22 and 30 that showed more than 80% anti-inflammatory
      activity were selected to study their analgesic, ulcerogenic and lipid
      peroxidation activities. All the tested compounds showed a significant reduction
      in ulcerogenic activity compared to ibuprofen through the severity index 0.5 to
      0.8, vs. ibuprofen 1.8. The compounds, that showed less ulcerogenic effect also
      produced less malondialdehyde content in gastric mucosa, which is one of the end
      products of lipid peroxidation. The results of biological studies showed that
      oxadiazole derivative 16 as the lead molecule with maximum anti-inflammatory,
      analgesic and minimum ulcerogenic and lipid peroxidation activities.

PMID- 19839406
TI  - Physicochemical characterization and in vitro dissolution behaviour of celecoxib
      beta-cyclodextrin inclusion complexes.
AB  - In this study, attempts were made to investigate the effects of beta-cyclodextrin
      (beta-CD) on the aqueous solubility and dissolution rate of celecoxib. Inclusion
      complexes were prepared by the kneading method and characterized by SEM, NMR, IR,
      DSC, and X-ray powder diffraction. Dissolution rate of the complexes was
      significantly greater than that of the corresponding physical mixtures and pure
      drug, indicating that the formation of inclusion complex increased the solubility
      of the poorly soluble drug celecoxib.

PMID- 19839407
TI  - Design and characterization of chitosan-containing mucoadhesive buccal patches of
      propranolol hydrochloride.
AB  - Mucoadhesive buccal patches containing propranolol hydrochloride were prepared
      using the solvent casting method. Chitosan was used as bioadhesive polymer and
      different ratios of chitosan to PVP K-30 were used. The patches were evaluated
      for their physical characteristics like mass variation, drug content uniformity,
      folding endurance, ex vivo mucoadhesion strength, ex vivo mucoadhesion time,
      surface pH, in vitro drug release, and in vitro buccal permeation study. Patches
      exhibited controlled release for a period of 7 h. The mechanism of drug release
      was found to be non-Fickian diffusion and followed the first-order kinetics.
      Incorporation of PVP K-30 generally enhanced the release rate. Swelling index was
      proportional to the concentration of PVP K-30. Optimized patches (F4) showed
      satisfactory bioadhesive strength of 9.6 +/- 2.0 g, and ex vivo mucoadhesion time
      of 272 minutes. The surface pH of all patches was between 5.7 and 6.3 and hence
      patches should not cause irritation in the buccal cavity. Patches containing 10
      mg of drug had higher bioadhesive strength with sustained drug release as
      compared to patches containing 20 mg of drug. Good correlation was observed
      between the in vitro drug release and in vitro drug permeation with a correlation
      coefficient of 0.9364. Stability study of optimized patches was done in human
      saliva and it was found that both drug and buccal patches were stable.

PMID- 19839408
TI  - Influence of process variables on release properties of paracetamol tablets.
AB  - A 2(3) factorial experimental design has been used to quantitatively study
      individual and interaction effects of the nature of binder (N), binder
      concentration (c) and relative density of tablet (d) on the disintegration time
      (DT) and dissolution times, t1, t50 and t90, of paracetamol tablet formulations.
      The factorial design was also used to study the quantitative effects of
      pregelatinization of starch binders on these parameters, i.e., N, c and d. In
      general, the most common ranking of the individual effects on DT, t1, t50 and t90
      for native/native, pregelatinized/pregelatinized and native/pregelatinized starch
      binder formulations was c > d > N. For interaction effects, the most common
      ranking was N-c > c-d > N-d for all formulations. The results generally showed
      that c can considerably affect DT, t1, t50 and t90 of the tablets.

PMID- 19839409
TI  - Rapid titrimetric and spectrophotometric methods for salbutamol sulphate in
      pharmaceuticals using N-bromosuccinimide.
AB  - One titrimetric and two spectrophotometric methods which are simple, sensitive
      and rapid are described for the assay of salbutamol sulphate (SBS) in bulk drug
      and in tablet dosage forms using N-bromosuccinimide (NBS) and two dyes, rhodamine
      B and methylene blue, as reagents. In titrimetry, aqueous solution of salbutamol
      sulphate is treated with a measured excess of NBS in acetic acid medium and after
      the oxidation of SBS is complete, the unreacted oxidant is determined
      iodometrically. Spectrophotometric methods entail addition of a known excess of
      NBS in acid medium followed by the determination of residual oxidant by reacting
      with a fixed amount of either rhodamine B and measuring the absorbance at 555 nm
      (method A) or methylene blue and measuring the absorbance at 665 nm (method B).
      In all methods, the amount of NBS reacting corresponds to the amount of SBS
      content. Titrimetric method is applicable over 1.74 x 10(-4) - 8.68 x 10(-4) mol
      L(-1) range and the reaction stoichiometry is found to be 1:6 (SBS:NBS). In
      spectrophotometric methods, the absorbance is found to increase linearly with the
      concentration of SBS, which is corroborated by the correlation of coefficients of
      0.9993 and 0.9988 for method A and method B, respectively. The systems obey
      Beer's law for 0.25-1.75 microg mL(-1) (method A) and 0.5-5.0 microg mL(-1)
      (method B). The calculated apparent molar absorptivity values were found to be
      2.10 x 10(5) and 6.16 x 10(4) L mol(-1) cm(-1), for method A and method B,
      respectively. The limits of detection and quantification are also reported for
      both spectrophotometric methods. Intra-day and inter-day precision and accuracy
      for the developed methods were evaluated. The methods were successfully applied
      to the assay of SBS in tablet and capsule formulations and the results were
      statistically compared with those of a reference method. No interference was
      observed from common tablet adjuvants. The accuracy and reliability of the
      methods were further ascertained by recovery experiments via the standard
      addition technique.

PMID- 19839410
TI  - Liquisolid technique as a tool for enhancement of poorly water-soluble drugs and
      evaluation of their physicochemical properties.
AB  - The potential of liquisolid systems to improve the dissolution properties of a
      water-insoluble agent (indomethacin) was investigated. In this study, different
      formulations of liquisolid tablets using different co-solvents (non-volatile
      solvents) were prepared and the effect of aging on the dissolution behaviour of
      indomethacin liquisolid compacts was investigated. To evaluate any interaction
      between indomethacin and the other components in liquisolid formulations, X-ray
      powder diffraction (XPD) and differential scanning calorimetry (DSC) were used.
      Dissolution test was carried out at two different pH, 1.2 and 7.2, to simulate
      the stomach or intestine fluid, respectively. The results showed that liquisolid
      formulations exhibited significantly higher drug dissolution rates at pH 1.2 and
      7.2 compared to compacts prepared by the direct compression technique. The
      enhanced rate of indomethacin dissolution from liquisolid tablets was probably
      due to an increase in wetting properties and surface area of drug particles
      available for dissolution. In order to investigate the effect of aging on the
      hardness and dissolution rate of liquisolid compacts, the formulations were
      stored at 25 degrees C/75% relative humidity for a period of 12 months. The
      results showed that aging had no significant effect on dissolution profiles of
      liquisolid tablets. Liquisolid compacts containing propylene glycol as vehicle
      produced higher dissolution rates in comparison with liquisolid compacts
      containing PEG 400 or Tween 80 of the same concentration. The DSC and XPD results
      showed no changes in crystallinity of the drug and interaction between
      indomethacin and excipients (Avicel and silica) during the process.

PMID- 19839411
TI  - Formulation of a self-emulsifying system for oral delivery of simvastatin: in
      vitro and in vivo evaluation.
AB  - The objective of the present work was to formulate a self-emulsifying drug
      delivery system (SEDDS) for simvastatin, which is widely used in the treatment of
      hypercholesterolemia and dyslipidemia as an adjunct to diet. Simvastatin SEDDS
      were formulated using a 1:1 (V/V) mixture of diesters of caprylic/capric acids
      and polyglycolyzed glycerides with varying concentrations of polyoxy castor oil
      and C8/C10 mono-/diglycerides. The developed SEDDS were evaluated for
      turbidimetry, droplet size analysis, drug content and in vitro diffusion
      profiles. In vivo performance of the optimized formulation was evaluated in rats
      using pharmacodynamic marker parameters like plasma total cholesterol (CH),
      triglycerides (TG) and high-density lipoprotein (HDL-CH) for 21 days. SEDDS
      containing 9.1% (m/m) simvastatin and 23.0% (m/m) of each excipient showed
      minimum mean droplet size (124 nm) and optimal drug diffusion. This test
      formulation showed significant reduction in plasma CH and TG (around 5-fold and 4
      fold, respectively), while HDL-CH concentration was markedly higher (2-fold)
      compared a reference simvastatin suspension formulation after oral administration
      for 21 days of study. Test formulation has shown enhanced pharmacodynamic
      performance compared to reference formulation in rats. The study illustrated the
      potential of simvastatin SEDDS for oral administration and its biopharmaceutic
      performance.

PMID- 19839412
TI  - In vivo antioxidant potential of Teucrium polium, as compared to alpha
      tocopherol.
AB  - The present study was undertaken to explore antioxidant potential of Teucrium
      polium (Lamiaceae) in vivo. Antioxidant activity was measured by three tests
      including inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, total
      antioxidant power (TAP), and thiobarbituric acid reactive substances (TBARS) in
      serum. Rats received dry extract of T. polium in 80% ethanol by intragastric
      intubation at doses of 50, 100 and 200 mg kg(-1) daily for 14 days. Treatment of
      rats with T. polium extract showed significant antioxidant activity in the DPPH
      test as compared to the control. T. polium extract at doses of 50 and 100 mg kg(
      1) significantly increased rats TAP and decreased TBARS compared to the control.
      Administration of T. polium at a dose of 200 mg kg(-1) per day did not
      significantly alter serum TAP and TBARS. Antioxidant activities of T. polium at a
      doses of 50 and 100 mg kg(-1) were in all experiments comparable to that of alpha
      tocopherol (10 mg kg(-1)).

PMID- 19839413
TI  - Evaluation and professionalism.

PMID- 19839414
TI  - Standards for the formulation of evaluative forensic science expert opinion.

PMID- 19839415
TI  - The kinetics of colour change in textiles and fibres treated with detergent
      solutions. Part I-Colour perception and fluorescence microscopy analysis.
AB  - The aim of this study was to assess colour changes that occur in several types of
      commonly available textiles as a result of the long-term effects of various
      popularly used laundry detergents. A 14 day experiment was conducted using blue,
      red and grey/black cotton, wool, acrylic and polyester textiles. Colour changes
      were evaluated through the visual comparison of the colour of the textile samples
      against that of the untreated (control) material. The kinetics of the changes in
      the colour of the fibres were monitored using fluorescence microscopy (UV
      excitation filter). The conclusions include an assessment of the observed changes
      from a fibre analysis expert's point of view, as well as that of an average
      user/consumer of the products involved.

PMID- 19839416
TI  - Development of a searchable major and trace element database for use in forensic
      soil comparisons.
AB  - Forensic soil comparisons are normally undertaken on the basis of several
      physical, chemical and biological properties, but in all cases the interpretation
      of results is dependent on the availability of relevant contextual information.
      This paper summarises the results of major and trace element analyses performed
      using inductively coupled plasma atomic emission spectrometry and inductively
      coupled plasma-mass spectrometry on the < 150 microm size fraction of 1896 soil
      samples collected in connection with forensic investigations in England and Wales
      between 1999 and 2007. A number of new methods are described which facilitate
      inter-sample comparison. Although the available data do not provide uniform
      geographical coverage they do provide useful information which can assist police
      search investigations and they provide valuable contextual information which aids
      the evidential assessment of soil evidence when used in court. There is
      considerable scope to improve the database by increasing the geographical
      coverage and increasing the number of soil attributes which are included.

PMID- 19839417
TI  - A preliminary investigation into the use of testate amoebae for the
      discrimination of forensic soil samples.
AB  - We present the results of an initial investigation into the efficacy of using
      testate amoebae for the discrimination of soils from wet ground and puddles, as
      little attention has been given to these organisms in forensic science. The
      preservation of testate amoebae in these sediments is generally good, although
      test concentrations are low. Statistical analysis suggests that testate amoebae
      assemblages are somewhat spatially distinct and have potential to be used for
      soil discrimination. A case study is presented where mineralogical (X-ray
      diffraction) and testate amoebae analyses are used in conjunction to clarify the
      scene of crime in a 'cold case' murder enquiry. Testate amoebae were recovered
      from dried sediment residues on clothing 10 years after the murder. Despite these
      promising results, further experimental work is crucial to examine the spatial
      and temporal variation of amoebae assemblages in water films, wet ground and
      puddles before they can be added to the armoury of methods available to the
      forensic biologist.

PMID- 19839418
TI  - Are facial image analysis experts any better than the general public at
      identifying individuals from CCTV images?
AB  - The aim of this study was to examine the accuracy and reliability of a small
      group of facial imagery experts, and compare their abilities with members of the
      general public, to ascertain whether or not training and experience will affect
      the ability to identify faces from CCTV footage. A number of clips from CCTV
      footage were utilised alongside face pools. The participants were asked to
      identify the actor in each CCTV clip and provide a level of confidence in the
      decision. The experts tested in this study were consistently better at
      identification than the public, with almost double the identification rates and
      half the errors. These results suggest that training and experience in facial
      analysis will produce more reliable and accurate facial identification.

PMID- 19839419
TI  - A preliminary investigation into the use of FTIR microscopy as a probe for the
      identification of bullet entrance holes and the distance of firing.
AB  - FTIR spectroscopy has been found to be a valuable probe for the analysis of the
      distribution of organic components such as nitroglycerine in gunshot residues
      deposited on and around the bullet entrance hole of the clothing of the victim in
      short range firearm discharges. The method can be utilised for the detection and
      estimation of organic gunshot residues (OGSR) on the hands and clothing of the
      shooter. The method is specific and sensitive and is likely to be free from
      interference from, for example, environmental pollution. The method shows
      potential to be utilised as a suitable alternative to the widely used SEM-EDX
      analysis of the total contents of lead, barium and antimony present in the
      gunshot deposits around the bullet entrance hole. The method was tested in the
      laboratory and the results were validated by Gas Chromatography-Mass Spectrometry
      (GC-MS).

PMID- 19839420
TI  - Identification of mongoose (genus: Herpestes) species from hair through band
      pattern studies using discriminate functional analysis (DFA) and microscopic
      examination.
AB  - India is home to seven species of mongoose (Herpestes sp). Mongooses are being
      poached primarily for their hair, which is used in the production of painting and
      shaving brushes. Prior to September 2002, mongooses were listed under Schedule-IV
      of the Wildlife (Protection) Act 1972 (India). Indiscriminate poaching of the
      mongoose created an immediate threat to their survival and hence mongooses have
      now been placed under Schedule-II of the Wildlife (Protection) Act-1972 (India).
      In order to convict a person under this legislation, species identification of
      case related samples is necessary. Four species of mongoose i.e. H. edwardsii, H.
      smithii, H. palustris and H. urva were characterised by performing discriminate
      functional analysis (DFA) on measurements of their dorsal guard hair banding
      pattern and by microscopic hair characteristics (Cuticular, medullar and cross
      section). It was possible to distinguish between the four species studied, based
      on both these methods.

PMID- 19839421
TI  - The "nudes murders" 1959-1965.

PMID- 19839422
TI  - Anti-doping researchers should conform to certain statistical standards from
      forensic science.
AB  - Anti-doping is currently viewed as a forensic science. However, close examination
      shows that the statistical treatment of evidence is inconsistent with that view.
      Here it is insisted that anti-doping researchers should conform to certain
      statistical standards from forensic science.

PMID- 19839423
TI  - Research, evaluation & interpretation. Robinson Executive Conference Centre,
      Wyboston, 31 October-2 November 2008.

PMID- 19839424
TI  - Controversies in the management of localized prostate cancer: after the rhetoric.

PMID- 19839425
TI  - Radical radiotherapy for prostate cancer is the 'only way to go'.
AB  - Management options for localized prostate cancer include radical prostatectomy
      (RP), radiation therapy (external-beam radiation therapy [EBRT] or
      brachytherapy), with and without androgen-deprivation therapy (ADT), or active
      surveillance, also known as watchful waiting. Ultimately, the choice of treatment
      is determined by a variety of factors, including institutional preference,
      individual physician judgment, patient preference, and resource availability. In
      this editorial, we make the case for radiation therapy (EBRT or brachytherapy) as
      the management modality of choice for localized prostate cancer.

PMID- 19839426
TI  - Optimal therapy in localized prostate cancer: an unfolding story.

PMID- 19839427
TI  - Radical prostatectomy reigns supreme.
AB  - The clinical incidence of prostate cancer continues to increase in the patient
      population, while the actual mortality has remained relatively low. As
      clinicians, we struggle to identify those patients who require intervention for
      their disease and to determine which treatment modality is best. Active
      surveillance, brachytherapy, external-beam radiation therapy, and surgical
      radical prostatectomy (RP) are the current options for prostate cancer treatment,
      each with a distinct impact on a patient's health-related quality of life. We
      believe that for the majority of patients with organ-confined prostate cancer, RP
      remains the gold standard with respect to both oncologic success and maximization
      of quality of life. Herein we discuss the advantages of RP.

PMID- 19839428
TI  - Localized prostate cancer: the battle of treatment options enters the larger
      arena.

PMID- 19839429
TI  - Neoadjuvant chemotherapy for resectable non-small-cell lung cancer.
AB  - Lung cancer generally has an unfavorable prognosis. For those with resectable
      disease, the use of neoadjuvant chemotherapy has the potential to reduce tumor
      volume, address micrometastatic disease early, and improve outcomes. Randomized
      trials comparing neoadjuvant platinum-based regimens with surgery alone were able
      to demonstrate the feasibility and safety of this modality. These trials
      supported evidence found in phase II trials that utilized third-generation
      chemotherapies. Still, limitations to these studies exist, such as the inclusion
      of various disease stages in one study, inter- and intratrial variability of the
      chemotherapy regimens used, and lack of phase III data comparing neoadjuvant to
      adjuvant chemotherapy. These heterogeneous factors make it difficult to offer
      firm recommendations about neoadjuvant chemotherapy. Other matters of contention
      include the role of postoperative radiation and the concern for increased
      postoperative complications, especially when a right pneumonectomy is being
      considered after neoadjuvant chemotherapy. To clarify these issues, well
      structured phase III trials comparing adjuvant to neoadjuvant chemotherapy are
      needed.

PMID- 19839430
TI  - Preoperative therapy for early-stage NSCLC: opportunities and challenges.

PMID- 19839431
TI  - More questions about neoadjuvant chemotherapy in lung cancer.

PMID- 19839432
TI  - Complementary therapies, herbs, and other OTC agents.

PMID- 19839433
TI  - Reassessing privacy and security compliance. ARRA provisions require
      organizations re-examine procedures and training.

PMID- 19839434
TI  - ARRA and the HIM workforce.
AB  - The success of health IT will hinge on how well it is planned and managed.
      Provisions in the stimulus bill that promote professional support and fund
      training offer exceptional opportunities to HIM programs, individuals, and the
      profession.

PMID- 19839435
TI  - Reducing healthcare disparities. How HIM workforce diversity helps.
AB  - HIM professionals can play an important role in reducing disparities in care that
      result from race and ethnicity. One practical step is by increasing the diversity
      of the HIM workforce.

PMID- 19839436
TI  - Professional practice experience. Internships open the door to real-world
      lessons.
AB  - For senior HIM students, a professional practice internship offers real-life
      experience and a firsthand look at future careers. But PPEs require sites that
      volunteer as hosts and HIM professionals to serve as mentors.

PMID- 19839437
TI  - Integrating ARRA. Leveraging current compliance efforts to meet the new privacy
      provisions.

PMID- 19839438
TI  - Tackling ARRA's privacy provisions. How one organization is addressing the new
      requirements.

PMID- 19839439
TI  - The standards value chain. Where health IT standards come from.

PMID- 19839440
TI  - The consumer view of PHRs. Observational study finds most value PHRs, but issues
      remain.

PMID- 19839441
TI  - Transitioning ICD-10-CM/PCS data management processes.

PMID- 19839442
TI  - Planning organizational transition to ICD-10-CM/PCS.

PMID- 19839443
TI  - Differentiating procedure approach in ICD-10-PCS. Fifth character captures
      specificity.

PMID- 19839444
TI  - CDI opportunities for HIM professionals.

PMID- 19839445
TI  - The simplest way to reboot your brain.
AB  - Research shows that even a few minutes of sleep can improve memory and problem
      solving skills. In light of the potential benefits to productivity and
      performance, you may want to encourage your employees to catch a few winks during
      the day.

PMID- 19839446
TI  - The five traps of performance measurement.
AB  - Evaluating a company's performance often entails wading through a thicket of
      numbers produced by a few simple metrics, writes the author, and senior
      executives leave measurement to those whose specialty is spreadsheets. To take
      ownership of performance assessment, those executives should find qualitative,
      forward-looking measures that will help them avoid five common traps: Measuring
      against yourself. Find data from outside the company, and reward relative, rather
      than absolute, performance. Enterprise Rent-A-Car uses a service quality index to
      measure customers' repeat purchase intentions. Looking backward. Use measures
      that lead rather than lag the profits in your business. Humana, a health insurer,
      found that the sickest 10% of its patients account for 80% of its costs; now it
      offers customers incentives for early screening. Putting your faith in numbers.
      The soft drinks company Britvic evaluates its executive coaching program not by
      trying to assign it an ROI number but by tracking participants' careers for a
      year. Gaming your metrics. The law firm Clifford Chance replaced its single, easy
      to-game metric of billable hours with seven criteria on which to base bonuses.
      Sticking to your numbers too long. Be precise about what you want to assess and
      explicit about what metrics are assessing it. Such clarity would have helped
      investors interpret the AAA ratings involved in the financial meltdown. Really
      good assessment will combine finance managers' relative independence with line
      managers' expertise.

PMID- 19839447
TI  - Making time off predictable--and required.
AB  - People in professional services believe a 24/7 work ethic is essential for
      getting ahead--and so they work 60-plus hours a week and stay tethered to their
      Black-Berrys. This perpetuates a vicious cycle: Responsiveness breeds the need
      for more responsiveness. When people are always "on," responsiveness becomes
      ingrained in the way they work, expected by clients and partners, and even
      institutionalized in performance metrics. There is no impetus to question whether
      the work actually requires 24/7 responsiveness; on the contrary, people work
      harder and longer, without stopping to explore how they could work better. But
      four years of research conducted by the authors in several North American offices
      of the Boston Consulting Group suggests that consultants and other professionals
      can provide the highest standards of service and still have planned,
      uninterrupted time off. They can do this even in times of recession. In this
      article, Perlow and Porter outline the lessons from BCG's implementation of
      predictable time off--namely, impose a strict mechanism for taking days and
      nights off, encourage lots of talk about what's working and what isn't, promote
      experimentation with different ways of working, and insist on top-level support.

PMID- 19839448
TI  - My turn: Hillary's good start.

PMID- 19839449
TI  - Ignoring the evidence. Why do psychologists reject science?

PMID- 19839450
TI  - [Influenza of ... 1889].

PMID- 19839451
TI  - [Interferon gamma and tuberculosis diagnosis: a real progress?].

PMID- 19839452
TI  - [Hereditary hemorrhagic telangiectasia].
AB  - Hereditary hemorrhagic telangiectasia (HTT, or Osler-Weber-Rendu disease) is a
      constitutional vascular dysplasia characterized by hemorrhagic manifestations,
      cutaneous or mucosal telangiectases and visceral shunting due to arteriovenous
      malformations. In France, its prevalence varies from 1/6,000 to 1/8,500. The
      diagnosis is clinical and based on the common triad: chronic epistaxis,
      responsible for anemias, cutaneous or mucosal telangiectases (on typical
      locations) and the hereditary nature of these signs inheredited in an autosomal
      dominant way. Penetrance is almost complete at 50 years. Visceral complications
      produce highly variable manifestations: pulmonary arteriovenous malformations may
      be manifested by brain abscess or transient ischemic attacks, signs of chronic
      hypoxia or hemorrhagic rupture; neurological arteriovenous malformations can
      produce signs of compression or be hemorrhagic; hepatic arteriovenous
      malformations, which remain latent for a long time, become clinically severe in a
      limited proportion of patients; hemorrhagic, digestive arteriovenous
      malformations worsen chronic anemia. HHT is a genetic disorder; two genes (ALK1
      and ENG) involved in the signaling pathway of the transforming growth factor-beta
      have been identified so far. Vascular homeostasis of capillaries is impaired,
      which leads to an accumulation in time of successive and progressive
      telangiectases and arteriovenous fistulas. Disease management consists in anemia
      management, as well as in epistaxis prevention and treatment. The management of
      arteriovenous malformations lies on early detection and the possibility to
      occlude them with interventional radiology.

PMID- 19839453
TI  - [Intravascular B cell lymphoma].

PMID- 19839454
TI  - [Listeriosis, a rare but severe foodborne infection].
AB  - Listeria monocytogenes is a Gram-positive bacillus widespread in nature and
      responsible for human and animal infections. Listeriosis is a severe and rare
      infection transmitted orally and vertically, frequently in the context of an
      underlying immunosuppression. L. monocytogenes is able to cross several barriers:
      intestinal mucosa, placenta and blood-brain barrier. Listeriosis is associated
      with a range of clinical presentations: ranging from acute gastroenteritis,
      septicaemia, central nervous system and maternofetal infections. Diagnosis is
      based on the isolation of L. monocytogenes from blood and cerebrospinal fluid
      cultures. Treatment relies on the synergic combination amoxicillin and
      gentamicin, with a mortality rate up to 30% despite adequate therapy.

PMID- 19839455
TI  - [Loiasis].

PMID- 19839456
TI  - [Lung cancers. One out of ten new cases of cancer in France].

PMID- 19839457
TI  - [What is new in the epidemiology of lung cancer: non-smokers, women and the role
      of cannabis?].
AB  - Lung cancer is in France, like in other countries, the first cause of death by
      cancer in men. It has become the third one in women in a few years span. If
      smoking is the main cause of lung cancer, other causes have been quite neglected
      for years such as occupational risk mainly asbestos exposure. Lung cancer in non
      smokers has increased during the last years. This may be a real increase or the
      consequence of ageing of the general population with increased incidence of lung
      cancer rather due to age than to tobacco. The considerable increase in women's
      incidence of lung cancer is partly due to the development of smoking habits since
      1960 in France. The possibility of an increased suceptibility to tobacco smoke in
      women is biologically plausible but still very controversial. The role of
      cannabis smoke is also controversial since it is very difficult to isolate the
      effects of cannabis which is in the majority of cases smoked with tobacco.
      However, recent studies are in favor of an independent role of cannabis in the
      development of lung cancers.

PMID- 19839458
TI  - [New diagnostic tools in lung cancers].
AB  - The diagnostic of lung cancer mainly relies on thoracic CT scan and bronchoscopic
      techniques. During the past decade, several improvements of these diagnostic
      tools have been made available, which aim to decrease the time to diagnosis and
      to simplify the initial staging approach. The diagnostic of peripheral lung
      nodules takes advantage of FDG PET-CT imaging as well as of recent per-endoscopic
      methods of peripheral lung nodule sampling such as electromagnetic navigation and
      endobronchial ultrasound. Autofluorescence or narrow band imaging bronchoscopy
      are helpful for the early diagnostic and monitoring of superficial cancers of the
      proximal bronchial tree. The diagnostic of intra-mediastinal lymph nodes has been
      simplified by the use of endobronchial ultrasound--transbronchial needle
      aspiration. In the near future, these techniques should reduce the need for
      invasive surgical procedures during lung cancer staging.

PMID- 19839459
TI  - [Standards of surgery in lung cancer].
AB  - Surgery has a pivotal role in the treatment of bronchogenic carcinoma. Indeed,
      resection is the standard treatment of early stages (I & II) non-small cell lung
      cancer, remains optional for a portion of patients with a locally advanced
      disease (IIIA & IIIB) and in anecdotal carefully selected patients with an
      oligometastatic disease (IV). In France, this surgery is framed by strict
      regulations. It is performed by qualified surgeons only, in authorized
      institutions, on the basis in particular of a minimal volume activity. The
      current risk of postoperative death is less than 5%, and the probability of 5
      year overall survival exceeds 60% in stage I patients. The standard surgical
      approach is an open thoracotomy. In poor-risk patients with stage I disease who
      are considered appropriate candidates for thoracoscopic anatomic lung resection,
      the use of video-assisted techniques is an acceptable alternative to open
      thoracotomy. In patients who are medically fit for conventional surgical
      resection, lobectomy or greater resections are recommended. Systematic
      mediastinal lymph node dissection should be performed for accurate pathologic
      staging and treatment. The practice of extended resections to mediastinal
      structures should be regionalized and reserved to high volume expert teams. The
      effort of standardization of surgical practices and the prospective collection of
      their results are necessary prerequisites for the evaluation of the quality of
      care.

PMID- 19839460
TI  - [Preoperative chemotherapy in non small cell lung cancer].
AB  - The combination of surgery with chemotherapy is the standard of care in stage II
      IIIa surgical non small cell lung cancer. The survival benefit of chemotherapy
      corresponds to 4 to 8%. This benefit has been proved mainly by postoperative
      chemotherapy trials. When the positive results were published, most preoperative
      chemotherapy trials were closed. Nevertheless, the same survival benefit could be
      expected in preoperative chemotherapy trials. Furthermore preoperative
      chemotherapy has advantages: compliance of chemotherapy is excellent and tumor
      chemosensibility can be estimated. As the sequence of chemotherapy and surgery is
      not yet established, the French recommendations of the SOR (Standards, Options
      and Recommendations) suggest either pre or postoperative chemotherapy.

PMID- 19839461
TI  - [Radiotherapy for non-small cell lung cancer].
AB  - Radiotherapy is a major therapeutic option in non small-cell lung cancer.
      Concurrent chemoradiation is the standard treatment of locally advanced
      unresectable tumours. Current modalities of thoracic radiotherapy include three
      dimensional conformal techniques, allowing dose escalation and combination with
      new generation cytotoxic drugs to occur. New techniques of radiotherapy are
      currently under development: respiratory gating and intensity-modulated
      techniques may allow a better focalisation of the ballistics; stereotactic
      radiotherapy and proton-beam radiotherapy, less available in Europe at the time,
      would be indicated in the exclusive treatment of early-stage tumours in non
      operable patients.

PMID- 19839462
TI  - [Treatment of metastatic non small cell lung cancer].
AB  - First line standard treatment of metastatic non-small-cell lung cancer is based
      on intravenous chemotherapy. Chemotherapy has been demonstrated to increase
      survival, to reduce symptoms and to improve quality of life. Bevacizumab, a
      monoclonal antibody inhibiting angiogenesis, improves survival when combined with
      chemotherapy. Because of a risk of hemoptysis, bevacizumab can only be delivered
      to non-squamous tumours with no proximal vascular invasion. Systemic treatment
      decision results from a multidisciplinary discussion and takes into account both
      patient (mostly performance status, age, and comorbidity) and tumour
      characteristics (histology, tumor location).

PMID- 19839463
TI  - [When to operate in metastatic non-small cell lung cancer].

PMID- 19839464
TI  - [Second line chemotherapy in metastatic non-small cell lung cancer].

PMID- 19839465
TI  - [Targeted therapies in second line treatment of metastatic non-small cell lung
      cancer].

PMID- 19839466
TI  - [Small-cell lung cancer].
AB  - Small-cell lung cancers represent 10 to 15% of lung cancers with a currently
      decreasing incidence. Various clinical presentations are possible, with a
      peculiar frequency of paraneoplastic syndromes. The work-up is based on the
      chest, abdomen and brain computed tomography scans. The standard of care is based
      on i.v. chemotherapy, and cisplatine plus etoposide remains the standard (6
      cycles). The standard of care includes thoracic radiotherapy in case of limited
      disease (at least 45 grays); prophylactic cranial irradiation is a standard of
      care in case of limited disease, and may be discussed in case of disseminated
      disease, for patients with a complete or an objective response. The standard of
      care for second line treatment is the topotecan.

PMID- 19839467
TI  - [Emotional consequences of psychological trauma].
AB  - The emotional consequences of psychological traumatisms are varied: major
      depression, anxiety disorders, addictive behaviour, adjustement disorders, and
      functional symptoms. The most severe traumatisms are likely to trigger an acute
      stress reaction which can lead to a chronic state called post-traumatic stress
      disorder. A rigorous clinical evaluation will determine not only the nature of
      the causal events but also the factors involved in the patient's emotional
      vulnerability elicited through his personal biography. Apart from specific
      psychiatric syndromes the treatment of adjustment disorders will rely mainly on
      social and psychological interventions; the use of psychotropic drugs will be
      prudent and limited in time.

PMID- 19839468
TI  - [Is psychological debriefing effective?].

PMID- 19839469
TI  - [Post-traumatic stress disorder and acute stress disorder].
AB  - Post-traumatic stress disorder (PTSD) is a disabling chronic disorder, which is
      often under-diagnosed, difficult to treat and to predict. The emotional and
      physical symptoms occur in three clusters: re-experiencing the trauma, avoidance
      of reminders of the event and hyperarousal for at least one month. Up to 80% of
      patients with PTSD have another psychiatric disorder. The main risk factors of
      PTSD are psychiatric and trauma history, trauma severity, peritraumatic
      dissociation and lack of social support. Treatment relies on psychotherapies like
      cognitive behavior therapy or EMDR and pharmacologic treatment like selective
      serotonin reuptake inhibitors without neglecting the forensic aspect.

PMID- 19839471
TI  - [Patients are becoming overinformed and chronic disease is increasing].

PMID- 19839470
TI  - [Managing patients with psychological trauma].
AB  - After having been neglected for a long time, taking care of victims has
      experienced an increasing interest for the last ten years (the creation of
      medicopsychological emergency cell [CUMP], the multiplication of professional
      trainings on this topic, the number and role of associations....). Aside from the
      political and social stake, the importance of psycho traumatic pathologies
      (consequences, co morbidity) justifies this interest. The caretaking of victims
      must be global (medical, social and judiciary) in order to optimize the
      accompanying all along the various actions thereby avoiding the hazards and
      misunderstandings which aggravate psycho traumatic troubles.

PMID- 19839472
TI  - [Uterine hemorrhage].

PMID- 19839473
TI  - [Ulcerations or erosion of the oral and/or genital mucosa. Diagnostic approach].

PMID- 19839474
TI  - [Eosinophilia. Diagnostic approach].

PMID- 19839475
TI  - [Red and/or painful eye].

PMID- 19839476
TI  - [Documentary research and self instruction. Rare diseases].

PMID- 19839477
TI  - [Mononucleosis. Diagnostic approach].

PMID- 19839478
TI  - [Child obesity].

PMID- 19839479
TI  - [Acute abdominal and lumbar pain in the adult].

PMID- 19839480
TI  - [Jean Dausset. Pioneer, discoverer and responsible].

PMID- 19839481
TI  - Influence of bleaching treatment on flexural resistance of hybrid materials.
AB  - The aim of this study is to evaluate the flexural resistance of three types of
      restorative materials: compomer (Freedom), resin-modified glass-ionomer
      (Vitremer) and composite resin (Esthet-X), observing whether the application of
      bleaching agent can cause alterations of their flexural properties. Sixty samples
      were made using a 10 x 1 x 1 mm brass mold, and divided into three groups: G1-
      Freedom (SDI); G2- Vitremer (3M ESPE); G3- Esthet-X (Dentsply). On half of the
      samples of each group (10 samples) the bleaching treatment was applied and the
      other half used as control, was stored in distilled water at a temperature of 37
      degrees C. Whiteness HP Maxx bleaching system was applied on the sample surface
      following the manufacturer's recommendations, simulating the bleaching treatment
      at the clinic. After this period, a flexural strength (three-point bending) test
      was conducted using (EMIC DL 1000) machine until the samples fractured. The data
      were submitted to ANOVA and Tukey tests. Of the restorative materials studied, G3
      (87.24 +/- 31.40 MPa) presented the highest flexural strength, followed by G1
      (61.67 +/- 21.32 MPa) and G2-(61.67 +/- 21.32 MPa). There was a statistical
      difference in flexural strength after the bleaching treatment. It was concluded
      that the use of a beaching agent can promote significant alteration of the
      flexural strength of these restorative materials.

PMID- 19839482
TI  - Dental beliefs in HIV+ patients with different oral health care needs.
AB  - The aim of this work was to assess the score variation of scales 1 and 2 of the
      DCBS (Dental Coping Beliefs Scale) of beliefs on oral health regarding oral
      health needs, clinical progression of the viral infection, medical care needs,
      age and gender in HIV+ patients. The DCBS was randomly administered to 102 HIV+
      patients at the "Juan A. Fernandez Hospital", Buenos Aires, Argentina. For each
      of the 29 items, patients indicated their responses on a five point scale ranging
      from "strongly disagree" to "strongly agree". Oral health needs were assessed
      through the CCITN (Community Caries Index of Treatment Need) and the CPITN
      (Community Periodontal Index of Treatment Need). Data on CD4 cell count,
      pharyngeal-esophageal candidiasis, tuberculosis, pneumonia and hospitalization
      because of HIV-related opportunistic diseases were recorded. A linear regression
      model was built in which the number of items reporting wrong dental beliefs was
      the dependent variable and the remaining variables were independent. Altogether
      65.7% were male (36.0 +/- 0.87 y.o.) and 34.3% were female (36.11 +/- 1.21 y.o.)
      patients. The eight independent variables were significant for the model
      (F(8.93)= 93.20, p < 0.05; R = 0.80). The estimated parameters were all positive
      except for CD4 cell counts. The results demonstrate that the DCBS was useful to
      identify HIV+ patients as a caries and periodontal disease risk group because of
      their wrong dental beliefs and suggests the need of dental education
      interventions.

PMID- 19839483
TI  - Fatigue analysis in the masseters and temporalis muscles in patients with
      temporomandibular disorder during short period of mastication.
AB  - The purpose of this experiment was to look for signals of muscle fatigue in
      volunteers with Temporomandibular Disorders (TMD) during short period of
      mastication. Twenty female volunteers selected by Research Diagnostic Criteria
      for Temporomandibular Disorders (RDC/TMD) participated, 10 with myogenic TMD
      (experimental) and 10 clinically normal (control). The Masseter and Temporalis
      muscles were evaluated electromyographically with active differential surface
      electrodes. The masticatory activity was recorded for 15 seconds and the signals
      were normalized by 4 seconds of teeth clenching. Three complete masticatory
      cycles were taken to calculating the median frequency (MF) and electromyographic
      amplitude (RMS). The data were submitted to statistics analysis and non
      parametric tests. The results showed that RMS and median frequency did not change
      during the mastication period analyzed, indicating the absence of muscle fatigue,
      for the Masseter and Temporalis muscles in both groups (p> 0.05). These results
      confirm the absence of signals of muscle fatigue in masticatory muscles during
      short period of mastication even in individuals with TMD, possibly due to
      increased of blood flow, consequence of dynamic muscle contraction and the
      individual characteristics of muscle fiber composition and recruitment.

PMID- 19839484
TI  - In vitro lethal photosensitization of S. mutans using methylene blue and
      toluidine blue O as photosensitizers.
AB  - The purpose of this in vitro study was to evaluate the antimicrobial effect of
      photodynamic therapy on Streptococcus mutans (A TCC 25175) suspensions, using a
      red laser for one minute in combination with toluidine blue O (TBO) or methylene
      blue (MB). Both photosensitizers were used in three concentrations (25, 10 and 5
      mg/L). The activity ofphotosensitizers and laser irradiation were tested
      separately on the bacteria, as well as the irradiation of this light source in
      the presence of the TBO or MB. These groups were compared to a control group, in
      which the microorganism did not receive any treatment. The activity of both TBO
      and MB or laser irradiation, alone, were not able to reduce the number of S.
      mutans. In the groups of lethal photosensitization, a bacterial reduction of 70%
      for TBO and 73% for MB was observed when these photosensitizers were used at 25
      mg/L and a reduction of 48% was observed for MB at 5mg/L. In other concentrations
      there were no significant differences in comparison to the control group. Both
      the TBO and the MB at 25 mg/L associated with a red laser had an excellent
      potential for use in PDT in lethal sensitization of S. mutans.

PMID- 19839485
TI  - Antibiotic resistance of periodontal pathogens obtained from frequent antibiotic
      users.
AB  - The occurrence of bacterial strains resistant to different antimicrobials is a
      growing problem in Latin American countries. The aim was to measure the
      antimicrobial susceptibility of Fusobacterium nucleatum, Prevotella intermedia
      and Prophyromona gingivalis, isolated from chronic periodontitis patients. Twenty
      five patients diagnosed with generalized- moderate or advanced- chronic
      periodontitis were consecutively recruited from patients attending the
      Periodontal Specialist Program, Javeriana University, according to specific
      criteria, including no recent antibiotic consumption. All patients filled out a
      questionnaire on antibiotic intake. The deepest periodontal pocket in each
      quadrant was sampled. Pooled samples were mixed, diluted and plated on enriched
      brucella agar plates. After anaerobic incubation, identification of the target
      bacteria was performed, based on colony morphology, gram staining, aerotolerance
      and biochemical reactions (RapID Ana II, Remel, U.S.A.). Following
      identification, the bacteria were subjected to antimicrobial testing, using
      amoxicillin, tetracycline, doxycicline, azithromycin and metronidazole (E-test,
      AbBiodisk, Sweden). The minimal inhibitory concentrations obtained were compared
      with a reference standard to determine antimicrobial resistance. Amoxicillin
      resistant species were tested for beta-lactamase production. Forty-four percent
      of the patients used antibiotics without any medical prescription, 40% used
      antibiotics at least once a year. The presence of eleven species was confirmed
      after a series of biochemical tests: four Fusobacterium nucleatum, five
      Prevotella intermedia and two Prophyromona gingivalis. All strains were resistant
      to metronidazole, five were resistant to tetracycline and azithromicin, and two
      strains were resistant to doxycicline and amoxicillin. The strains resistant to
      amoxicillin were positive for beta-lactamase production, Antimicrobial
      resistance, particularly against metronidazole, was a common phenomenon for the
      bacterial isolates analyzed in this Colombian sample.

PMID- 19839486
TI  - Changes in saliva protein composition in patients with periodontal disease.
AB  - Periodontitis is a chronic inflammatory disease characterized by tissue
      destruction which is usually diagnosed through clinical and radiographic signs.
      The detection of changes in the chemical composition of saliva could be used to
      reflect gingivo-periodontal alterations. The aim of this study was to identify
      salivary parameters that could identify different stages of the periodontal
      disease. The study group included 118 adults, 89 of them with mild, moderate or
      severe chronic periodontitis. The remaining participants comprised the control
      group. Total saliva was analyzed for physical and chemical properties. Dodecyl
      sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was used for protein
      detection and zymography for type IV collagenase identification. Salivary flow
      rate, pH and buffer capacity showed similar values in all groups. Proteins were
      augmented in severe periodontitis, as also shown by SDS-PAGE. Hydroxyproline rose
      significantly in all periodontal groups as secretory Immunoglobulin A
      significantly diminished compared with the control group. An increase in
      peroxidase was detected in moderate and severe periodontitis. All salivary
      samples contained 200-116-92 kDa gelatinases; minor bands at 66-31 kDa were also
      present in all periodontitis groups. Calcium levels showed significant
      differences between all periodontitis groups compared with the control group.
      Quantitative changes in the chemical composition of the saliva of patients with
      periodontal disease could be of significance in the diagnosis and progression of
      periodontal disease.

PMID- 19839487
TI  - Assessment of manipulation accuracy of digitized occlusal radiographic images-
      sub and over exposure.
AB  - The aim of this study was to evaluate whether digitized images obtained from
      occlusal radiographs taken with low or over dose of radiation could be improved
      with the aid of computer software for digital treatment. Thirteen occlusal
      radiographs of a dry skull were taken employing 13 different exposure times. The
      radiographs were digitized and then manipulated with the program for image
      editing. 143 evaluations were performed by specialists in dental radiology who
      classified radiographs as appropriate or not appropriate for interpretation. Test
      Z was used for statistical analysis of the data and the results showed that it is
      possible to manipulate digitized radiographic images taken with 75% of the ideal
      exposure time and to make them suitable for interpretation and diagnosis.
      Conversely, it was concluded that the over exposed images, 57.50% above the
      standard exposure time, were inadequate.

PMID- 19839488
TI  - Sealing ability of MTA used as cervical barrier in intracoronal bleaching.
AB  - The aim of this study was to compare the sealing ability of white mineral
      trioxide aggregate (MTA) with that of other materials used as a cervical barrier
      during intracoronal bleaching. Thirty eight extracted teeth were endodontically
      treated and 3 mm of filling was removed to receive the barrier material: G1
      Coltosol; G2 - Vidrion R; G3 - White MTA; G4-No barrier (negative control) and G5
      Roots totally protected with three layers of cyanoacrylate (positive control).
      The 30% hydrogen peroxide associated with the sodium perborate was left in the
      pulp chamber for 24 h. The specimens were immersed in a test tube containing a
      solution of potassium chromate (yellow), which turns blue in the presence
      ofhydrogen peroxide. Two calibrated evaluators scored according to color in the
      presence of the detecting solution (0 - unaltered color, 1 - light blue and 2 -
      dark blue). Data were analyzed by the Kruskall-Wallis test (p<0.05). The results
      showed no statistically significant differences between the experimental group G3
      and positive control (G5). No statistically significant difference was observed
      between G1 and G3. However a statistical difference was verified between G2 and
      G3. MTA presented higher sealing ability than Vidrion R and did not differ from
      the positive control. However there was no difference between MTA and Coltosol.

PMID- 19839489
TI  - Radiographic interpretation of unilocular radiolucent mandibular lesions.
AB  - The main goal of this study was to identify the main distinctive radiographic
      characteristics of different unilocular radiolucent mandibular lesions based on
      the criteria used by different groups of specialists during the process of
      radiograph interpretation to arrive at a correct diagnosis. A total of 24
      panoramic radiographs were selected exhibiting the following lesions:
      ameloblastoma, keratocystic odontogenic tumor, dentigerous cyst and simple bone
      cyst. Six cases of each pathology were analyzed by 3 specialists from 4 related
      areas (pathologists, stomatologists, radiologists and oral surgeons). A number of
      important distinctive features and confounding characteristics that are liable to
      misinterpretation were pointed out by the specialists during the analysis. The
      method of generalized estimating equations (GEE) was used to estimate the
      probability of correct diagnosis according to the specialization of the examiner
      and the type of lesion and no significant relation was found (p>0.05 for all
      variables). The overall percentage of correct diagnosis among the specialists was
      around 56%, which shows that these lesions are of difficult radiographic
      diagnosis. Although the specialty of the examiners did not influence the results,
      i.e., the 4 different kinds of specialists showed the same diagnostic capacity,
      the criteria used for interpreting the same lesions were often different among
      the specialists. The compilation of these criteria enabled the identification and
      selection of some useful distinctive radiographic characteristics to formulate
      diagnostic hypothesis of unilocular radiolucent lesions. The radiographic
      diagnosis of the unilocular radilucent mandibular lesions is particularly
      difficult and the histopathological examination is essential to make the
      definitive diagnosis.

PMID- 19839490
TI  - Antagonistic action of indigenous Streptococcus mutans strains.
AB  - Dental caries is an infectious process which ultimately destroys the tooth.
      Streptococcus mutans is considered to be the main agent causing this disease. If
      microorganisms with antagonistic action on S. mutans were found, they might
      provide a way of avoiding or controlling the disease. Within the framework of the
      Oral Microbial Ecology approach, the aim of this project was to identify S.
      mutans strains with antagonistic effect upon S. mutans. Saliva samples were taken
      from 66 children and cultured on Blood agar and Mitis Salivarius Bacitracin agar.
      They were incubated at 37 degrees C in anaerobic atmosphere for 48 hours, after
      which bacteria were counted and biochemical tests performed on colonies
      compatible with S. mutans. Antagonistic effect was determined using the double
      layer in agar technique. In children without and with caries, the frequency of S.
      mutans was 91.7% and 96.7%, respectively. In the group of patients without
      caries, only two strains had no antagonistic action, and three strains had full
      antagonistic action (100%), while the rest showed different kinds of inhibitory
      action. In the group of patients with caries, only 5 strains had no antagonistic
      action, 32 strains had full antagonistic action (100%) and the rest had variable
      inhibitory action. To conclude, 112 S. mutans strains with high antagonistic
      potential were identified, which, after other requirements are fulfilled, could
      be used in caries prevention or control strategies.

PMID- 19839491
TI  - Marginal fit analysis of premachined and castable UCLA abutments.
AB  - This study evaluated the fit between implants and premachined and castable UCLA
      abutments. All plastic specimens were cast using the conventional technique in
      accordance with the manufacturer's instructions. Five specimens of each
      experimental group were measured for vertical and horizontal gaps by scanning
      electronic microscopy (Phillips XL 30 model, Holland). Gold UCLA (vertical gap:
      2.15 microm, horizontal gap: 11.30 microm) and castable rotational UCLA (vertical
      gap: 14.91 microm, horizontal gap: 59.41 microm) groups showed the lowest and
      highest mean values, respectively (Neodent, Curitiba, Parana, Brazil). In
      general, the castable UCLA abutments showed poorer marginal fit than the
      premachined abutments.

PMID- 19839492
TI  - Clinical and microbiological characteristics in predicting dentine caries
      progression.
AB  - The purpose of this study was to evaluate the clinical aspect of dentine and its
      microbiota in predicting caries progression. The sample consisted of
      schoolchildren in the 7 to 14 years age group. Treatment involved cavity
      preparation trough the clinical criterion of hardness, with the collection of
      carious and remnants dentine for microbiological analysis. The clinical aspect
      (color and consistency) of the dentine remmants was recorded and the teeth were
      restored using silver amalgam and glass ionomer cement as pulpal protector
      (baseline - BL). After 1 year the restoration was removed and after new clinical
      and microbiological analyses, the teeth were then restored. Microbiological
      samples were collected at both time-points and cultivated in sheep blood agar, in
      anaerobiosis for 48 hours. Bacterial growth was analyzed quantitatively.
      Semiquantitative and qualitative analysis of the bacteria was performed by
      hybridization with genomic DNA probes and the checkerboard method. A significant
      difference was observed between the aspect of dentine remnants at BL and at 1
      year (p=0.0078). The amount of bacteria at BL and at 1 year did not differ
      significantly (p= 0.37) and the microbiota of the carious dentine was
      predominantly composed of Gram-positive cocci. The removal of carious dentine
      based on the clinical criterion of hardness, followed by a well-adapted
      restoration, would determine the non-progression of caries. The few bacteria that
      still remained in the cavity would be no longer viable.

PMID- 19839493
TI  - Evaluation of metered-dose inhaler administration technique among asthmatic
      children and their caregivers in Thailand.
AB  - Ninety-three asthmatic children and their caregivers were studied on their
      techniques of inhaler administration. Factors associated with the correct use of
      the device were also evaluated. Only 55.9% of the studied children demonstrated
      the correct technique in using their inhalation devices. In children using MDI (n
      = 42), the most common incorrect performance was the step of breathing in slowly
      at the same time with actuation (n = 17, 40.5%). Among those who used MDI-spacer
      (n = 51), all medication was given by their caregivers. The most common error was
      the step of waiting for 30 seconds prior to the next MDI actuation (n = 13,
      25.5%). Factors related to the correct performance included duration of use for
      more than 1 year (p = 0.02), instruction of inhalation technique by trained
      technicians (p = 0.04) and the education level of the caregivers (p = 0.01). Our
      study demonstrates that incorrect technique during inhalation is common among
      Thai children with asthma and emphasizes an essential role of health
      professionals in regular evaluation of their patients and caregivers to ensure
      their correct application.

PMID- 19839494
TI  - Urticarial vasculitis: etiologies and clinical course.
AB  - Out of 64 patients diagnosed with urticarial vasculitis (UV), 49 (76.6%)
      presented with their first attack of UV. The others experienced recurrent attacks
      with a mean number of 3.3 past recurrences. Fifteen patients had angioedema
      (23.4%) and 16 (25%) suffered systemic involvement. The most common abnormal
      laboratory finding was an increased erythrocyte sedimentation rate. Six of 62
      patients (9.7%) had decreased C3 levels. A cause could be identified in 19
      patients (29.7%). The most common identified cause was infection; other causes
      included drugs, malignancy and systemic lupus erythematosus (SLE). The prevalence
      of immunoreactant deposits in the skin lesions measured by DIF was 54.7% (35 of
      64 patients). The median disease duration of each episode was 85 days. The
      probability that patients were free of symptoms within one year was 70%. Patients
      with an idiopathic cause had a statistically significant longer course duration
      of each episode than the group with upper respiratory tract infection. Compared
      to reports from Westem countries, our patients seemed to have less severe
      symptoms and a lower percentage of hypocomplementemic UV and SLE.

PMID- 19839495
TI  - Is silent sinusitis a cause of chronic urticaria in children?
AB  - The etiologies of chronic urticaria (CU) comprise a wide variety of disorders
      including chronic infections. The association of sinusitis and CU is
      controversial due to the lack of a control group. The objective of this study was
      to investigate the role of silent sinusitis as a cause of CU in children. A sinus
      X-ray (SXR) was performed in 107 children with CU. SXR abnormalities were found
      in 52.3% of the patients. Nine patients (8.4%) had symptoms of sinusitis and were
      treated with amoxicillin/clavulanate. Five of these patients (55.6%) had CU
      remission. Forty-seven patients (43.9%) who had an abnormal SXR without sinusitis
      symptoms were randomized into treated (23 patients) and control (24 patients)
      groups. Eighteen patients (78.3%) in the treated group and 15 patients (62.5%) in
      the control group had CU remission (p = 0.24). These data did not support a
      causal relationship of sinusitis and CU in children.

PMID- 19839496
TI  - The natural history and prognostic factors of egg allergy in Korean infants with
      atopic dermatitis.
AB  - The aim of this study was to understand the natural course of egg allergy and to
      identify the prognostic factors for tolerance. A retrospective study that
      included 106 children with atopic dermatitis and egg allergy diagnosed at less
      than 2 years of age was conducted using medical records and parental telephone
      interviews. Tolerance was defined as the absence of an allergic reaction in
      response to the parental introduction of cooked eggs to the diet of children
      whose egg white specific IgE level had decreased to less than 1.5 kU(A)/l. The
      median age of tolerance to egg allergy was 4 years. Kaplan-Meier analysis
      predicted that 41% of children had developed tolerance to egg allergy by age 3,
      while 60% of children had developed tolerance by age 5. The age at the diagnosis
      of egg allergy was the only significant prognostic factor of egg allergy
      tolerance identified by the Cox proportional regression model.

PMID- 19839497
TI  - Wheat-dependent, exercise-induced anaphylaxis in Thai children: a report of 5
      cases.
AB  - Wheat is not an uncommon cause of food-dependent, exercise-induced anaphylaxis.
      This study aims to describe common clinical characteristics and laboratory
      manifestations of the disease. Five children, aged 8-14 years were evaluated. An
      atopic history was found in 20% of the patients. All patients had symptoms which
      involved the skin and three had hypotension. Serum specific IgE for wheat was
      measured and showed a positive result in 2 patients. A three-day challenge
      protocol with an open challenge for wheat on day 1, an exercise challenge test on
      day 2 and another exercise challenge test on day 3 after a meal containing wheat
      was performed. Four patients completed the three-day challenge protocol.
      Anaphylaxis occurred in 2 out of 4 patients who consumed more than 100 grams of
      wheat prior to the exercise. The three-day challenge protocol is a definitive
      diagnostic tool to confirm the diagnosis of WDEIA. However, the amount of wheat
      used for challenging should be at least 100 grams.

PMID- 19839498
TI  - IgE-binding reactivity of peptide fragments of Bla g 1.02, a major German
      cockroach allergen.
AB  - Cockroaches cause allergic diseases and are closely linked with the development
      of asthma. Bla g 1 is one of the major allergen proteins produced by German
      cockroaches. It consists of tandem repeats of approximately 100 amino acids. The
      aim of the present study was to identify linear IgE-binding epitopes of Bla g
      1.02. RT-PCR was used to clone a cDNA sequence encoding Bla g 1.02 (EF202179)
      which shared 98.6-99.8% identity with a previously reported Bla g 1.02
      (AF072220). To investigate IgE binding regions, five separate but overlapping Bla
      g 1.02 peptide fragments (A: aa 1-111, B: aa 102-215, C: aa 206-299, D: aa 289
      403, E: aa 394-491) were amplified and cloned. The full-length and five peptide
      fragments were overexpressed in Pichia pastoris and E. coli, respectively, and
      their IgE binding reactivities were measured by ELISA using 37 serum samples
      isolated from cockroach-sensitized patients. The sera of 24 patients (64.9%)
      recognized the full-length Bla g 1.02 recombinant protein. Among 19 selected
      serum samples, 11 sera (57.9%) reacted to peptide fragment A, 5 sera (31.3%) to
      B, 4 sera (21.1%) to C, 9 sera (47.4%) to D, and 10 sera (52.6%) to peptide
      fragment E. IgE-binding epitopes are found to be distributed to each tandem
      repeat of Bla g 1. The combination of peptide fragments A, D, and E may able to
      detect all Bla g 1-sensitized subjects. We suggest that these peptide fragments
      may be useful in allergy diagnosis and the design of novel immunotherapeutics.

PMID- 19839499
TI  - Clinical manifestations of Kawasaki disease: what are the significant parameters?
AB  - The initial differential diagnosis of Kawasaki disease (KD) from other acute
      febrile illnesses infants and children is particularly difficult in patients who
      exhibit incomplete criteria. The objective of this study was to determine the
      differences in the clinical and laboratory findings between KD patients and those
      who were initially sus- , pected of having KD but eventually had other diagnoses.
      One hundred and fourteen pediatric patients who were initially diagnosed with
      suspected KD were included. Eighteen cases were finally diagnosed with another
      disease. The only demographic data that were significantly different between the
      groups were body height and the duration of fever. The KD group exhibited more
      classical clinical criteria than those who were finally diagnosed with another
      disease. The erythrocyte sedimentation rate (ESR) and platelet count were
      significantly higher in the KD group than in the non-KD group. An ESR > or = 40
      mm/hour had a diagnostic sensitivity of 90.5%, a specificity of 66.6%, a positive
      predictive value of 93.4%, and a negative predictive value of 57.1%. The
      incidence of coronary aneurysm in this study was 6.2%. There was no correlation
      between ESR and coronary aneurysm. We conclude that the clinical criteria are the
      basis for the diagnosis of Kawasaki disease but the ESR can be helpful in
      pediatric patients with acute febrile illness who do not exhibit all clinical
      criteria.

PMID- 19839500
TI  - Analysis of Foxp3, CD25, and CD127 expressed on regulatory T cells in Thai
      subjects.
AB  - Foxp3+ natural regulatory T cells (nTreg) play a distinct role in maintaining
      self tolerance at the periphery. CD25hi and CD127lo were proposed for the
      identification and purification of nTreg but they have not been confirmed in non
      Caucasian populations. This study examined the sensitivity and purity of Foxp3
      nTreg identified by CD25 and CD127 in the peripheral blood of Thai subjects (13
      males, 15 females with age range of 20-42 years old). The proportions of
      nTreg/CD4+ as identified by the different markers were as follows: Foxp3+, 18.3
      +/- 6.4%; CD25hi 6.4 +/- 3.2%; and CD127lo, 54.3 +/- 14.2%. Sensitivity tests
      showed the following results: CD25hi, 23.1%; CD127lo, 40.6%; CD25hiCD127lo, 7.4%.
      Purity tests concluded as follows: CD25hi, 63.6%; CD25int, 24.9%; CD2510, 8.7%,
      CD127lo, 26.5%; CD127hi, 14.9%, and CD25hiCD127lo, 52.0%. In conclusion, the
      proportions of nTreg in Thai subjects are similar to Caucasian populations.
      CD25hi is superior to CD127lo for separating Foxp3+ nTreg. Combining CD25hi and
      CD127lo does not improve the nTreg purity.

PMID- 19839501
TI  - Proliferation index in tuberculous lymphadenitis.
AB  - During the pathogenesis of any granuloma, activated macrophages (AMs) are
      recruited and expanded under the influence of the migration inhibition factor.
      The goal of this study was to determine whether AMs then also proliferate by
      themselves or not. The proliferation index (PI) of AMs in lymph node biopsies
      from 40 cases of tuberculous lymphadenitis was evaluated by immunohistochemistry
      using a monoclonal antibody (MIB-1) to Ki-67. The PI was defined as the
      percentage of AMs with positive nuclear staining. It ranged from 3.6-20.6% (mean
      = 11.0 +/- 4.4) which was slightly lower than that reported in previous studies.
      Mitotic figures ranged from 0-6 per 500 AMs. Multinucleated giant cells ranged
      from 0-6.3 cells per low power field and their PI was exclusively 0%. Areas of
      caseous necrosis ranged from 5-85% of the total area of the tissue section
      examined (mean = 61.6 +/- 19.8). Mitotic figures, multinucleated giant cells, and
      areas of caseous necrosis lacked a statistically significant relationship to the
      PI (p > 0.05). In conclusion, AMs in granulomas can proliferate to a limited
      degree as detected by the mitotic figures and the PI.

PMID- 19839502
TI  - High prevalence of Hepatitis C virus genotype 6 in Vietnam.
AB  - This study aimed to update the prevalence of the various Hepatitis C virus
      genotypes in Vietnamese blood donors. One hundred and three HCV antibody-positive
      plasma samples were collected from blood donors at the National Institute of
      Hematology and Blood Transfusion, Hanoi, Vietnam. All specimens were subjected to
      RT-PCR of the 5' untranslated region (UTR) to confirm the presence of HCV RNA.
      The core and NS5B regions of thh positive samples were subsequently amplified by
      RT-PCR followed by direct sequencing and phylogenetic analysis. Seventy out of
      103 samples (68.0%) were RNA positive. Core and NS5B were successfully amplified
      and sequences were obtained for 70 and 65 samples, respectively. Phylogenetic
      analysis revealed that genotype 6a was the most predominant among Vietnamese
      blood donors with a prevalence of 37.1% (26/70), followed by genotype 1a at 30.0%
      (21/70) and genotype 1b at 17.1% (12/70). The prevalence of two other genotype 6
      variants, 6e and 61 was 8.6% and 1.4%, respectively. Further analysis of recent
      studies showed that the geographic distribution of genotype 6 covered mainly
      southern China and the mainland of Southeast Asia including Vietnam, Laos,
      Thailand, and Myanmar. The GenBank accession numbers for the sequences reported
      in this study are FJ768772-FJ768906.

PMID- 19839503
TI  - A novel mutation of the IL12RB1 gene in a child with nocardiosis, recurrent
      salmonellosis and neurofibromatosis type I: first case report from Thailand.
AB  - Genetic defects of interleukin (IL)-12/23-and interferon (IFN)-gamma-mediated
      immunity can cause increased susceptibility to intracellular microbes. Among
      these defects, a mutation of the gene encoding the IL-12 receptor beta1 (IL
      12Rbeta1) is the most common worldwide. A 12-year old Thai boy with pre-existing
      neurofibromatosis type 1 (NF1) was evaluated for primary immunodeficiency after a
      history of tuberculous lymphadenitis, recurrent Salmonella infections and
      nocardiosis. Flow cytometry of phytohemagglutinin (PHA)-stimulated peripheral
      blood mononuclear cells (PBMCs) revealed a defect in the IL-12Rbeta1 surface
      expression. A genetic study showed a novel nonsense homozygous mutation of the
      IL12RB1 gene in exon 4 (402C > A), confirming the diagnosis of IL-12Rbeta1
      deficiency. This is the first case report of a primary IL-12Rbeta1 deficiency in
      Thailand with the interesting finding of a coexisting NF1.

PMID- 19839504
TI  - Epidemiology and current status of allergic rhinitis, asthma, and associated
      allergic diseases in Korea: ARIA Asia-Pacific workshop report.
AB  - The prevalence of allergic rhinitis and asthma has recently increased in Korea,
      and both conditions are recognized as major chronic respiratory diseases
      requiring active intervention. The prevalence of rhinitis among asthmatic
      patients is high, ranging from 60 to 80%, and could seriously affect asthma
      severity and outcome. We suggest that allergic rhinitis should be properly
      evaluated in asthmatic patients to achieve better asthma control.

PMID- 19839505
TI  - [Myofacial pain and tension-type headache].
AB  - The current epidemiological data indicate that at least 20% of the adult
      population suffer from frequent and returning headaches. The latest
      classification elaborated by the International Headache Society (IHS)
      distinguishes more than 80 different kinds of headaches in 14 groups (the second
      edition). The statistics show that about 30-78% of the cause of these disorders
      is the tension-type headache (NBG), which turns into chronic state (PNBG) of
      about 3%. The etiology and the likelihood mechanism of rising this kind of pain
      is being discussed for many years now and it awakes many controversies. At
      present, the research workers agree that the peripheral pain mechanism is
      responsible for rising NBG however at the base of PNBG lies the persistent
      activation of the peripheral nociceptors by intervention of which it comes to
      stimulation of central neurons. In confirmation of the muscular origin of NBG and
      the attempt of stating the new course to take with patients there are works of
      Simons and co-workers that describe myofascial pain. Myofascial pain is explained
      as a state of functional disorders which is bred by active trigger points (which
      breed pain after a fixed pattern) and latent points that being about disorders
      without pain effect. The treatment of myofascial pain is based on restoring the
      proper biochemistry and physiological length of the myofascials elements.

PMID- 19839506
TI  - Hodgkin's disease--the rare cause of nephrotic syndrome in children.
AB  - PURPOSE: Hodgkin's disease (HD) is a potentially curable malignant lymphoma with
      distinct histology, biologic behavior and clinical characteristics. Renal
      involvement in HD is rare, but it may be underestimated because renal lesions are
      not the major manifestation of the disease. The pathogenesis of proteinuria in HD
      remains unknown. CASE REPORT: The case of a 17-year-old girl suffering from
      Hodgkin's disease and nephrotic syndrome has been described. CONCLUSION: The
      authors would like to underline the very rare coincidence of Hodgkin's disease
      and nephrotic syndrome, the lack of remission after routine prednisone
      administration and disappearance of nephrotic proteinuria after anticancer
      therapy.

PMID- 19839507
TI  - [Motor and speech functions and their connections in children during the first
      stage of the development of the central nervous system].
AB  - Developmental task is the most common diagnostic tool used in children with
      developmental disturbances. It follows according to physiology of the development
      of the child. Transition through the "mile stones" describes the development of
      the child in four areas-motor, speech, social and visuo-motor coordination.
      Systematic diagnostic researches allowed preparation of detailed developmental
      schemas - motor and psychomotor intelligence. The aim of the work was to present
      some normal rules of development in motor and speech areas and its biological
      bases in first years of life. The work presents connections between motor and
      speech development on a sample of assimilation and accommodation processes
      described by Piaget.

PMID- 19839508
TI  - [Vesicoureteric reflux: it all depends on the genes?].
AB  - Vesicoureteric reflux (VUR) defined as reversed urine flow from the urinary
      bladder to ureter(s) and frequently to kidneys is associated with abnormal
      structure and/or malfunction of one or both ureterovesical junctions. In the
      pediatric practice, VUR constitutes an important problem not only because of
      prevalence but also because of the role it plays in pathogenesis of urinary tract
      infections, reflux nephropathy and chronic renal failure in children. Recent
      reports confirm genetic background of vesicoureteric reflux. Vesicoureteric
      reflux is inherited as a dominant autosomal disease (with possible incomplete
      gene(s) penetration). The Authors present a review of recent literature with
      focus on key role of candidate genes in the development of VUR in children.

PMID- 19839509
TI  - [Laryngological effects of palatal suture expansion].
AB  - INTRODUCTION: The aim of the study was the assessment of the influence
      ofmidpalatal or maxillary suture expansion on laryngeal and audiologic changes in
      treated patients. MATERIAL AND METHOD: The study comprised 30 patients, 19 female
      and 11 male aged from 10 years 6 months to 30 years 1 month. All of them were
      treated for severe maxillary constriction by the use of rapid maxillary expansion
      with palatal suture opening. The laryngeal and audiologic assessment has been
      based on specialized consultations and self-assessment of the examined patients.
      RESULTS: After palatal suture expansion, an improvement in free nasal breathing
      assessed by the examined patients has been observed in 82% patients from group I
      and 67.67% patients from group II. After palatal suture expansion, an improvement
      in conductive hearing impairment ranging 15-20 dB has been observed in all
      examined patients, who had that disorder before the treatment. CONCLUSIONS:
      Palatal suture expansion has improved statistically and significantly free nasal
      breathing as estimated by the examined patients. After palatal suture expansion
      an improvement in conductive hearing impairment has been observed ranging 15-20
      dB. The improvement in conductive hearing impairment was due to restored normal
      function of the openings of the auditory tubes. No statistically significant
      influence of palatal suture opening on the size of enlarged palate and pharyngeal
      tonsils and uprighting of deviated nasal septum has been observed.

PMID- 19839510
TI  - [Occurrence and risk factors of musculoskeletal pain and sport injuries in
      students of physical education in University of Szczecin].
AB  - PURPOSE: The aim of the study was to investigate the occurrence of
      musculoskeletal pain and sport injuries and also to find their risk factors among
      students of physical education of the University of Szczecin. MATERIAL AND
      METHODS: The study was conducted in students of physical education of the
      University of Szczecin and it was based upon a questionnaire. Of all 525
      students, 503 (95.8%) responded the questionnaire, 218 women (43.3%), 285 men
      (56.7%). The questionnaire involved questions on the musculoskeletal complaints,
      participation in sports and its character, sport injuries with their localization
      and associated sport discipline, anthropometric, socio-economic and life style
      data, psychosocial profile. The univariate stepwise regression analysis,
      multivariate stepwise regression analysis, U Mann-Whitney test and chi2 test were
      used for statistical evaluation of the data. The odds ratio was calculated for
      chosen variables with 95% confidence interval. RESULTS: Almost half of the men
      and women reported the presence ofmusculoskeletal pain in the previous year. Both
      women and men claimed the most frequently knee pain, shoulder and ankle pain.
      Altogether 236 students reported sport injuries, 92 (42.4%) women and 144 (50.5%)
      men. The students reported the total number of 1065 injuries. Men claimed
      significantly more injuries then women. The most important risk factors for
      musculoskeletal pain were sport injuries. The psychosocial factors significantly
      influenced the occurrence of pain. Participation in certain sports was the main
      risk factor of injuries in students. Also participation in competitive sport was
      the risk factor for injuries of knee, ankle, feet and shoulder joints.
      CONCLUSIONS: 1. Musculoskeletal pain is common in the studied population. 2.
      Sport injuries are the most important risk factor of musculoskeletal pain in this
      group. Participation in certain sport disciplines and psychosocial factors are
      also risk factors ofmusculoskeletal pain. 3. Sport injuries were reported by
      nearly half of the students, the most common localization of injuries were knee
      and ankle joints. 4. There are specific injuries related in this group to
      participation in some sports, and also to participation in competitive sports.

PMID- 19839511
TI  - [The current state of knowledge about pathomechanism of tennis elbow].
AB  - The term tennis elbow applies to the state in which the patient feels pain in the
      area of lateral epicondyle and concomitantly suffers from strength disorders
      together with diminished capability of the upper limb. Even a very brief look at
      the specialist literature reveals that there is a number of terms for this
      particular pain unit. Throughout many years this pain was linked with the
      inflammation of the common extensors tendon. Presently there is a widespread
      agreement that this painful condition is connected with the degeneration in the
      area of common extensors tendon, in particular the extensor carpi radialis
      brevis. A closer consideration of the pathomechanism of the tennis elbow points
      to the fact that this seemingly simple pain unity is a complex problem. Moreover,
      it shows how important the nuances in patients opinion are and how such details
      can influence not only the diagnose but also the treatment.

PMID- 19839512
TI  - [Dry skin as a dermatological and cosmetic problem].
AB  - The paper presents current opinions on aetiopathogenesis of dry skin including
      its occurrence in the course of certain dermatological disorders. A meaning of
      natural moisturizing factor, lipid barrier as well as epidermal differentiation
      processes in the maintenance of the proper skin moisturization is described. The
      importance of topical treatment is emphasized. Moreover, a survey of moisturizing
      factors applied in dry skin care is included.

PMID- 19839513
TI  - [Cleanliness of the root canal walls after preparation with Mtwo rotary nickel
      titanium instruments: a SEM study].
AB  - INTRODUCTION: The aim of this study was to evaluate the cleanliness of the walls
      of root canals following their preparation using Mtwo nickel-titanium rotary
      instruments. MATERIAL AND METHODS: The study was performed on 5 mesial roots of
      mandibular molars and 3 buccal roots of maxillary molars with moderate
      curvatures. The canals were instrumented using Mtwo nickel-titanium rotary files
      powered by the endodontic micromotor to a size 30/.05. During instrumentation
      FileEze was used as a lubricant and after each instrument the canals were
      irrigated with solution of natrium hypochlorite. The final flushing was performed
      with distilled water and the canals were dried. The roots were splitted
      longitudinally into halves and prepared for SEM observation. Debris and smear
      layer were evaluated in the apical, middle and coronal parts of the root canal
      walls using a 5-point scales proposed by Hulsmann et al. Established data were
      analysed statistically. RESULTS: Evaluation of debris revealed in high number of
      scores 1. Evaluation of the removal of the smear layer revealed in smaller amount
      of it in coronal parts of the root canals (scores mainly 3 and 4) and in greater
      amount in apical parts (scores mainly 4 and 5). CONCLUSION: It was found that
      under the conditions of the present study Mtwo instruments successfully removed
      debris, although they left canal walls covered with smear layer.

PMID- 19839514
TI  - [Dental status, parodontium condition and occurrence of malocclusions in
      conscripts from the West Pomeranian Voivodship, Poland].
AB  - INTRODUCTION: System transformation in Poland after 1989 began the series of
      changes in the country, both favorable and negative in relation to the health of
      oral cavity. The aim of this study was to collect the up-to-date information in
      realtion to the occurrence and intensity of the most common diseases and
      disorders of the masticatory system in the West-Pomeranian population of young
      males, as well as the evaluation of degree of achievement of WHO targets for a
      year 2000 and a chance of reaching WHO targets for a year 2010. MATERIAL AND
      METHODS: Dental research was carried out on the group 720 conscripts, aged 18-19
      years, from the West-Pomeranian Voivodship in Poland. RESULTS: Frequency of the
      caries in the examined group amounted to 98.62% and did not differ significantly
      in relation to the place of residence and formal education. The coefficient of
      the caries treatment was 0.47. The full dentition was maintained only by 78.47%
      of the examined young people. The healthy parodontium was observed only in 22.64%
      boys. Only 1/3 of the examined did not have malocclusion, and orthodontic
      treatment was recommended for 32.78% of the young people. Abnormalities in the
      functioning of temporal-mandibular joints was observed in 49.17% young people.
      CONCLUSIONS: We observed essential differences in the state of the masticatory
      organ, in relation to the place of residence and education. Conscripts from the
      West-Pomeranian voivodship, Poland, did not reach WHO targets for this age group
      for a year 2000, in relation to the health of the oral cavity.

PMID- 19839515
TI  - [Selected aspects of quality of life of patients treated for neoplasms of oral
      cavity].
AB  - INTRODUCTION: Neoplasms of oral cavity make up 2.4% of all neoplasms in male and
      1.1% in female population of Poland. Treatment of neoplasms in this area is
      mainly surgical and leads to a smaller or larger disability with a disorder of
      basic physiological functions such as breathing, swallowing and speech. It leads
      as well to the creation of psychological symptoms such as anxiety, depression.
      Lack of available data in Polish literature as well as in foreign literature on
      the subject of psychological state and quality of life of those patients,
      convinced me to start research in this area. MATERIAL AND METHODS: The research
      was conducted on a group of 131 patients aged 44-82 years. The patients were
      divided into three groups: group I consisted of patients after surgical
      procedures in the face area, group II of patients with serious prognosis
      (leukaemia) and group III of healthy patients. All patients were subject to
      survey, which consisted of 2 parts. First part contained 7 questions and related
      to patient's knowledge as to prognosis for further life (this part pertained
      patients from group I and II). Second part of the questionnaire was a shortened
      version of a depression scale based on 15 traits and short version based on 4
      traits. It was adopted, that this is a good research tool in case of depression,
      since it is directed exclusively on diagnosis of depression symptoms. Short
      research technique facilitates the patient to answer questions asked. The results
      were interpreted according to depression rating scale. RESULTS: The research
      indicated that amongst patients after surgical procedures; over 50% of women and
      almost 40% of man showed intensified growth of depression. This percentage was
      significantly lower in the group of patients with serious prognosis. In the
      healthy group, all of the women and over 80% of men had no depression. Education
      statistically had no significant influence on the depression level. CONCLUSION:
      It can be ascertained that surgical procedures in the facial area and oral cavity
      have influence and generate patient's depression. Therefore, the care over those
      patients should be multispecialistic.

PMID- 19839517
TI  - Endodontic treatment of complicated traumatic deciduous teeth damage--a case
      report.
AB  - The 11-year-old boy was diagnosed with severe external root resorption of the
      tooth 11 and chronic exacerbated apical periodontitis of the tooth 12.
      Additionally, the tooth 12 showed signs of dilaceration. The history revealed
      that at the age of 5, the boy had dislocated his maxillary deciduous incisors
      with impaction to the tissues. The root canal treatment of the teeth 11 and 12
      was performed with the application ofBiopulp, Jodoform, and Metronidazole paste
      to the canal. The dressings were changed every 4 weeks for 6 months. The root
      canals of both teeth were filled with the Resilon Epiphany System. The root apex
      of the tooth 11 was additionally sealed with Pro Root MTA preparation. Defects in
      crowns were closed with composite material. On followup examination (6 and 12
      months after the beginning of the treatment), the patient did not complain of any
      pain. The radiological picture showed complete healing of periapical structures
      of the tooth 12 and lack of resorption progress in the tooth 11.

PMID- 19839516
TI  - [Oral cavity health condition of HIV carriers].
AB  - INTRODUCTION: Acquired Immune Deficiency Syndrome (AIDS) is a disease, which
      damages the cell immunity of an organism. Changes in the oral cavity have an
      important role in the diagnostics of contagion. The aim of the paper was the
      assessment of the state of the oral cavity of the patients who had HIV. They had
      also antiretroviral and immunomodulating treatment. MATERIAL AND METHODS: 90
      people, aged from 20 to 60, residents of Zachodniopomorskie region, were members
      of the examined group. They were divided into three groups. The intensity of the
      dental caries was assessed and an average PUW number. The history of the previous
      dental services was done. Also patients' stomatological needs were assessed.
      Medical services were assessed according to index of stomatological treatment and
      its structure. Additionally, oral cavity was evaluated with the use of plaque
      index. State and treatment needs of the paradontium were evaluated with the use
      of CPITN index. RESULTS: The indicator of caries, cavity and filling average
      values were statistically not essential in all the groups. Caries active dental
      caries was present in every group. The average number of extracted teeth was
      higher than in the control group. It is statistically essential. The average
      number of filled teeth of people with and without treatment was lower than in the
      control group. That was statistically essential. The rise of the medical services
      structure values index shows that the number of tooth extracting services is
      becoming proportionally higher to other effective stomatological services. The
      gained results show the inadequate stomatological treatment of the infected. The
      level of hygiene was higher in the group of not infected people than in the group
      of the people with HIV, who were undergoing antiretroviral treatment.
      CONCLUSIONS: Patients with HIV were characterised by the low level of hygiene of
      the oral cavity and by the bad state of teeth. Extractions of the teeth of the
      infected people were the most often stomatological services. Too low oral cavity
      hygiene of the people with HIV influences the state of their teeth. The highest
      requirements of the paradontium stomatological services are in the group of
      patients who are taking antiretroviral medicines.

PMID- 19839518
TI  - [Endodontic treatment or dental implant treatment?].
AB  - INTRODUCTION: The main purpose of today's dental treatment is the longest
      possible retention of teeth with all its functional and esthetic aspects. Thanks
      to modern endodontic techniques and microsurgical procedures, it is possible
      today to treat and keep teeth that would have had to be extracted before. On the
      other hand, the latest development of forms and surfaces of dental implants,
      improved operation techniques and precision in preparing superstructures have
      determined a significant increase of percentage of successful implantations and
      survival rate of the implants, widening the range of possibilities of prosthetic
      reconstructions. The aim of this study is to present current, often ambiguous
      view on the problem of long-term effects of endodontic treatment and its impact
      on teeth retention compared with effects of dental implant treatment and to try
      to answer the question: extirpation or implantation? MATERIALS AND METHODS: The
      comparative research was based on studies published within two databases: PubMed
      and Medline. RESULTS: Studies from a 10 years' period show similar percentage of
      surviving teeth after endodontic treatment and surviving implants: between 86 and
      94 per cent with slight advantage of the implants. Esthetic problems, the time
      needed for implantation procedures and high costs of implant treatment make
      implantation less attractive and accessible. However, anatomical limitations
      ofmultirooted teeth, extensive periapical granulomatic lesions or considerable
      crown and root destruction are all indications for implant treatment. The lack of
      clear-cut evaluation criteria regarding both endodontic and implant treatment
      success makes statistic analysis impossible.

PMID- 19839519
TI  - [The diagnostic value of oblique technique for periapical radiography and its
      usefulness in endodontic treatment].
AB  - The applicability of the intraoral X-rays in the oblique projection during the
      endodontic treatment is described in this study. The rules concerning the
      positioning of the X-ray tube, intraoral film and the examined tooth, necessary
      to obtain images in mesial and distal oblique projections are discussed. The
      usefulness of the aforementioned projections in visualizing the anatomy,
      anomalies as well as periapical changes of the dental roots and canals during the
      endodontic treatment is presented.

PMID- 19839520
TI  - [Serum anti-p53 antibodies and CEA in monitoring of recurrences of colorectal
      cancer].
AB  - INTRODUCTION: Little is known regarding the behaviour of serum anti-p53
      antibodies (p53 Ab) in postoperative follow-up of patients with colorectal
      carcinoma and whether it can be used as an additional marker. The aim of this
      study was to evaluate usefulness of p53 Ab and CEA level for postoperative
      monitoring of recurrence or metastasis in patients after surgery due to
      colorectal cancer with normal pre-operative CEA levels and anti-p53 anitbodies.
      MATERIAL AND METHODS: The research group consisted of 124 patients with
      colorectal cancer diagnosed on the basis of histopathological or cytological
      examination. Colonoscopy, abdominal ultrasound, serum CEA and anti-p53 antibody
      tests were done at the time of diagnosis and every 6-month from surgery. RESULTS:
      The occurrence of recurrence or metastasis was preceded by the appearance of anti
      p53 antibodies 6 months earlier on average, in 5 patients, and the increased CEA
      level was preceded 9 months earlier on average, in 7 patients. The relationship
      between the increased CEA level and the occurrence of recurrence or metastasis
      was statistically significant (p < 0.0001); however statistically significant
      relationship was not found in the case of anti-p53 antibodies assessment.
      Performing these two tests simultaneously, at the same time with the same
      patients caused the increase of accuracy of recurrence or metastasis from 0.45 to
      0.68. CONCLUSION: Multiple assessments of both serum p53 Ab and CEA during
      postoperative monitoring increase the probability of early detection of
      recurrence or metastasis in patients with colorectal cancer and normal CEA level
      before surgery.

PMID- 19839521
TI  - [Oxidative stress and trace elements affect the activity of sodium transporting
      systems in a cellular membrane of a erythrocyte].
AB  - We examined the activity of sodium transporting systems (STS) in a cellular
      membrane of erythrocytes in a group of 21 patients under chronic hemodialysis
      treatment with the dialyzing fluid containing glucose HD-g(+), and 22 patients
      dialysed with the fluid not containing glucose HD-g(-), 21 patients with chronic
      kidney failure already not treated with dialysis and 21 control group. We
      examined the concentration of antioxidative system cofactors, such as zinc,
      copper and selenium in erythrocytes and plasma. The marker of oxidative stress in
      erythrocytes and plasma was the concentration of TBARS. Among all STS we examined
      the activity of Na(+)/K(+) ATP-ase, Na(+)/K(+)/Cl(-); co-transport, Na(+)/Li(+)
      exchanger, Na(+), K(+)-outflow. Copper zinc and selenium as cofactors of
      antioxidative enzymes may reflect the antioxidative processes inside the organism
      undergoing the influence of free radicals.

PMID- 19839522
TI  - CHEK2 germline mutations correlate with recurrence rate in patients with
      superficial bladder cancer.
AB  - BACKGROUND: Some bladder cancers can be the result of genetic predisposition or
      chromosomal abnormalities, but no clinical useful molecular marker exists to
      identify patients with higher risk ofrecurrence. We analyzed the recurrence rate
      in patients with three variants of tumor suppressor gene mutation, checkpoint
      kinase 2 (CHEK2). The endpoint of the study was to evaluate the rate, risk of
      recurrence and free-recurrence survival during 24-months observation time in
      CHEK2 positive (CHEK2+) and control group. MATERIAL AND METHODS: The observation
      group consisted of 24 CHEK2+ patients among 445 treated on account of bladder
      cancer. Patients with > or = T2 and/or G3 disease were excluded from the study.
      Control group included 44 consecutive patients with superficial bladder cancer
      (SBC). Clinical data were collected from the patients' clinical records and
      correlated with chromosomal studies. RESULTS: Tumor grade had no impact on risk
      of recurrence. Stage T1 revealed to be the strong recurrence predictor until 15th
      month of follow-up when compared to stage Ta. CHEK2 mutations strongly correlated
      (odds ratio = 6.47; p = 0.08) with the risk of recurrence comparing to T1 stage
      (OR = 1.49), and grade 2 (OR = 0.85). CHEK2 factor was also significant risk
      factor for the number of recurrences in particular periods of follow-up.
      CONCLUSIONS: The results indicate that patients with CHEK2 mutation may present
      poorer clinical course with several recurrences of SBC. It also suggests a
      possible prognostic significance of CHEK2 analysis in identifying patients with
      higher risk of recurrence, which may imply more aggressive treatment modalities
      or necessity of modified follow-up schedule.

PMID- 19839523
TI  - Conjugated dienes of linoleic acid and tumorigenesis.
AB  - Conjugated dienes of linoleic acid (CLA) are fatty acids widely found in food of
      animal and plant origin. CLA has been the subject of extensive investigation
      regarding its possible benefits on a variety of human diseases. This short review
      summarizes the state of knowledge about the anticancer and antitumor properties
      of the CLA.

PMID- 19839524
TI  - [Androgenetic alopecia in women as an aesthetic and psychological problem].
AB  - Androgenetic alopecia is a fairly common disorder which causes serious aesthetic
      and psychological problems. The paper discusses the etiology, diagnostics and
      possible treatment of androgenetic alopecia in women. Preparations for both
      general and external use in treatment of this dermatosis have been presented
      herein.

PMID- 19839525
TI  - [Polydactyly and syndactyly as the most common congenital disorders of the
      limbs].
AB  - Polydactyly is a common hereditary disorder in which extra or vestigial digits
      are present on the one or both sides of the extremities. It is ten times more
      frequent in Blacks than in Whites. Polydactyly occurs both in a sporadic form and
      in a hereditary form. In polydactyly type A, the extra digits contains phalanges,
      in polydactyly type B, there is no skeletal structure. The extra digit is made by
      skin only. Syndactyly type I exists when the connection is at the level of skin,
      in type II the phalanges of the fingers are connected. For syndactyly correction,
      combined use of "Z"-method incision and full-thickness free skin grafts are the
      most common method of treatment. A new method is based on a straight incision and
      free skin grafts. The scars after the serial excision are placed on the
      midlateral lines. The final scars are minimal, and good functional and cosmetic
      result is obtained.

PMID- 19839527
TI  - [Scientific publications of the Pomeranian Medical University in Szczecin for
      year 2006].

PMID- 19839528
TI  - [The state of family care].

PMID- 19839529
TI  - [EbM from the bottom up: are questions asking for evidence in daily clinical
      practice answerable?---a report from a pilot test to assist general practitioners
      with using evidence-based medicine].
AB  - Many physicians agree on the advantages of using Evidence-based Medicine (EbM) in
      daily practice, but they do not make use of this method very often. One reason
      for this lack of EbM implementation is that it is difficult to access clinically
      relevant and appropriate information in daily practice. The division "Principles
      and Practices of EbM" in the German Network for Evidence-based Medicine (DNEbM)
      initiated a pilot project to improve their information management. During two
      weeks in February 2007 physicians in a local setting in the southeast part of
      Germany were offered an EbM expert service. They were asked to formulate open
      ended questions arising from daily practice. Seventeen experts answered these
      questions within a three day period. In addition, all participants regularly
      received an edited version of these topics, and finally a questionnaire was sent
      out to evaluate physician satisfaction. Five family doctors and two hospital
      departments formulated 28 questions in two weeks. There was a wide range of
      answers, from evidence summaries (including full texts of the trials or relevant
      guidelines) up to expert opinion together with a discussion of different action
      strategies in the case of uncertain evidence. The participating physicians'
      satisfaction with this offer of low-barrier access to the best available evidence
      and the answers provided by the experts was high. Apart from the suggested
      solutions to the respective problems the project initiated a critical self
      analysis of their individual clinical practice among the participating
      physicians. All of them saw the need for continuing this project. Further
      investigations are needed in order to optimise both the process of EbM
      implementation on a long-term basis and the health care quality by providing EbM
      expert services.

PMID- 19839530
TI  - [Inadequate reimbursement and the patients themselves may inhibit the
      implementation of guidelines. Evaluation of the venous leg ulcer guideline of the
      German Society of Phlebology (DGP) in general and phlebology practices].
AB  - AIM: The S3-guideline for diagnosis and treatment of venous leg ulcers published
      by the German Society for Phlebology (DGP) in 2006 was tested for its acceptance
      and practicability in outpatient care delivered by general practitioners (GPs)
      and phlebologists. Barriers to the implementation of the guideline's
      recommendations in regular health care were identified. METHODS: Qualitative
      research using focus groups and interviews by telephone; systematic content
      analysis of records and transcripts by two independent researchers. RESULTS:
      Altogether, GPs and phlebologists gave a positive evaluation of the guideline,
      but it also became clear that it does not form the basis of their everyday work
      practice. Factors inhibiting the application of the guideline included the
      insufficient reimbursement systems and the patients' compliance, but these
      factors were weighed differently between the two groups. Evidence-based
      performance seems to play a minor role with regard to patients suffering from leg
      ulcers in daily practice. CONCLUSION: Barriers of implementation as well as
      detailed suggestions by the users will help to revise and to adapt the guideline
      to the needs of both users and patients.

PMID- 19839531
TI  - [Overweight patients in primary care: how family physicians utilize medical check
      up examinations for risk counselling. Content analysis of check-up counselling
      talks between physicians and patients].
AB  - BACKGROUND: The number of overweight patients in Germany has been continuously
      increasing during the past years. The so-called "check-up 35" consultation
      presents primary care providers with an opportunity for preventive counselling
      talks with the respective individuals. In this qualitative study we analysed
      family physician encounters. We were particularly interested in the way in which
      the subject matter was addressed and the risk counselling performed by the
      physicians when confronted with overweight patients. METHODS: Twelve physicians
      audio-taped their final check-up dialogue with 52 overweight or obese patients
      (BMI > or = 25 kg/m2). The interviews were transcribed, and a content analysis
      was conducted using the established method developed by Mayring. RESULTS:
      Physicians used direct or more often indirect strategies to address overweight in
      counselling talks that were most often initiated by their patients. They largely
      addressed this topic while communicating laboratory results. Some obese patients
      did not receive any advice on health risks. In the encounters analysed the
      physicians did not employ standardized risk counselling tools. CONCLUSIONS: The
      reasons for addressing overweight indirectly and the lack of standardized risk
      counselling with obese patients are carefully discussed.

PMID- 19839532
TI  - [Factors associated with influenza vaccination information--a cross-sectional
      study in elderly primary care patients].
AB  - General practitioners (GPs) play an important role in influenza vaccination.
      However, reliable data on the influenza immunisation coverage rate in primary
      care patients are quite rare. Due to a lack of personal and time resources
      general practitioners cannot afford to collect such data by themselves. Hence
      fifth-year students have been involved in the scientific data collection during
      their practical placement in 118 GP practices. Using logistic regression analysis
      of a representative sample (n = 541) plausible factors associated with the
      influenza immunisation coverage rate have been identified. These factors were
      found to be both patient- and practice-specific. This practice-oriented study was
      conducted to improve the available data base on the influenza immunisation
      coverage rate among elderly patients in primary care settings.

PMID- 19839534
TI  - [Problems and deficits in the transition from inpatient to outpatient care of
      cancer patients].
AB  - INTRODUCTION: Initiated by the Public Health Department of the City of Aachen
      problems and deficits in the transition from hospital-based to outpatient care of
      cancer patients were evaluated. METHOD: From September 2002 to April 2003 the
      data of 145 cancer patients who met the inclusion criteria and had been treated
      in four regional hospitals were collected by questionnaire, phone and personal
      interview at four different points in time within a period of six to eight weeks
      and documented. Aspects of interest included: type of disease, symptom burden,
      well-being, home care situation and medical aids required. RESULTS: Problems and
      deficits in the transition from hospital-based to outpatient care of cancer
      patients were only infrequently encountered. Specific structural deficits or
      general problems were not identified. The majority of patients felt comfortable
      with their medical transition process. For a special subgroup of patients who
      died during the trial period worse outcomes were documented than for the whole
      sample. DISCUSSION: Worse outcomes of the dying patients indicate disease
      progression with reduced quality of life, higher symptom burden and less
      satisfaction. The complex study method and the resulting selection bias may have
      contributed to underestimating transition problems. A more simple method could
      reduce the burden for the patients and the amount of missing data and thus allow
      for a deeper insight into the patients' needs.

PMID- 19839533
TI  - [Metabolic control in patients with type-1 and type-2 diabetes mellitus receiving
      ambulatory care from general practitioners: results of a cross-sectional trial
      performed in the German federal states of Thuringia and West Pomerania].
AB  - Up to the present moment there has been a large controversy over the metabolic
      control in patients with type-1 and type-2 diabetes mellitus receiving ambulatory
      treatment from general practitioners. Hence this trial aimed to assess the
      parameters of treatment quality in patients under ambulatory care in two German
      regions. PATIENTS AND METHODS: A total of 2,242 patients from 25 general
      practitioners' care units were assessed from October 1998 to September 1999.
      RESULTS: The mean age of the patients was 67.5 +/- 13.1, and the mean diabetes
      duration was 8.8 +/- 7.5 years. 26.1% of the patients were treated without using
      anti-diabetic drugs, and 44.2% took oral anti-diabetic medications. 20.0%
      received insulin alone and 9.5% a combination therapy of insulin and oral anti
      diabetic agents. The mean HbA1c of 6.9 +/- 1.5 was comparable in Thuringia and
      West Pomerania. It was measured in 68.4% of the patients. Blood pressure values
      were documented in 98.8%. A total of 31.6% of patients took part in structured
      diabetes treatment and teaching programmes. In Thuringia the percentage of
      patients under specialized diabetes care was 3.6%; in West Pomerania it was
      significantly lower (18%, p<0.001). CONCLUSION: The quality of treatment and
      metabolic control in patients with type-1- and type-2 diabetes mellitus receiving
      ambulatory care from general practitioners is much better than is commonly
      assumed. However, as indicated by the relatively low frequency of HbA1c
      measurements, the treatment quality is far from reaching the requirements of
      national guideline recommendations.

PMID- 19839535
TI  - [The Bellagio Model: an evidence-informed, international framework for population
      oriented primary care. First experiences].
AB  - The Bellagio Model for Population-oriented Primary Care is an evidence-informed
      framework to assess accessible care for sick, vulnerable, and healthy people. The
      model was developed in spring 2008 by a multidisciplinary group of 24 experts
      from nine countries. The purpose of their gathering was to determine success
      factors for effective 21st century primary care based on state-of-the-art
      research findings, models, and empirical experience, and to assist with its
      implementation in practice, management, and health policy. Against the backdrop
      of "partialization", fragmentation in open health care systems, and the growing
      numbers of chronically ill or fragile people or those in need of any other kind
      of care, today's health care systems do not provide the much needed anchor point
      for continuing coordination and assistance prior, during and following an episode
      of illness. The Bellagio Model consists of ten key elements, which can make a
      substantial contribution to identify and overcome current gaps in primary care by
      using a synergetic approach. These elements are Shared Leadership, Public Trust,
      Horizontal and Vertical Integration, Networking of Professionals, Standardized
      Measurement, Research and Development, Payment Mix, Infrastructure, Programmes
      for Practice Improvement, and Population-oriented Management. All of these
      elements, which have been identified as being equally necessary, are also alike
      in that they involve all those responsible for health care: providers, managers,
      and policymakers.

PMID- 19839536
TI  - [Cluster randomised trials: an important method in primary care research].
AB  - In primary care research interventional studies often address organisational
      changes or educational interventions, for example, in the context of guideline
      implementation. For pragmatic reasons randomisation is often conducted at
      practice level instead of at the individual patient level. Patients from one
      practice form a cluster, thus violating the basic assumption of independent
      patient samples. Hence an increased number of participants and a more complex
      analysis are required. Using the example of two cluster randomised trials the
      present article provides insights into the advantages and disadvantages of
      cluster randomisation as well as its practical significance for the planning and
      analysis of cluster randomised trials.

PMID- 19839537
TI  - ["Healthy Region Lower Rhine ... against Stroke": the concept and implementation
      of an intersectoral public health programme 2003-2008].
AB  - BACKGROUND AND AIMS: When the Public Health Service Act of North Rhine-Westphalia
      (OGDG-NRW) came into effect local health conferences (KGK) were established in
      both rural and urban districts. These conferences are designed to optimize
      medical and social healthcare at the local level. In 2001 KGK managers from six
      neighbouring districts founded the Network Healthy Lower Rhine. From 2003 to 2008
      this network was able to implement the "Healthy Lower Rhine ... against Stroke"
      programme. The initiative primarily aims at improving community knowledge of
      stroke with regard to 1) proper action ("Stroke is a medical emergency, so call
      the emergency number 112!") and 2) stroke warning signs. Eventually these steps
      are intended 3) to reduce prehospital delays. METHODS: Before the program started
      a project plan was developed including evaluation approaches. The central
      elements of the concept include local health targets, intersectoral collaboration
      and networking, 5-year programme duration, social marketing and a communication
      strategy. Initially, a needs assessment was conducted using local expert panels,
      surveys on community knowledge, and clinical data sampling to assess healthcare
      quality. Subsequently, a package of measures with a "two-level implementation
      model" was prepared. Normative evaluation consisted of self-reflection within the
      network-team. The summative evaluation was based on two approaches: surveys on
      community knowledge of stroke (city of Dusseldorf and district of Wesel) as well
      as data sample collection in hospitals on health care quality. RESULTS: The
      central elements of the concepts were implemented. Community surveys revealed
      similar deficits in community knowledge of stroke in the city of Dusseldorf (2000
      and 2004) and in the district of Wesel (2002 and 2008). Knowledge of proper
      action (call 112 in case of stroke) significantly improved in the Dusseldorf
      community from 32.5% of correct statements in 2000 to 50.6% correct answers in
      2004 and, finally, in 2008 to 69% correct answers in the Wesel district.
      Hospitals in the district of Wesel collected three-month samples of data on
      prehospital times in 2003 (before the initiative was started) and in 2005. There
      was no significant change: the portion of 28% of patients being hospitalized
      within a three-hour window after the onset of stroke symptoms remained unchanged.
      DISCUSSION: Due to medical progress and demographic changes stroke remains a
      paramount issue of public health in Germany. With its programme "Healthy Lower
      Rhine ... against Stroke" the Network Healthy Lower Rhine provides a strategy for
      launching and implementing a complex and intersectoral public health
      intervention.

PMID- 19839538
TI  - [Tuberculin therapy in ambulatory treatment].

PMID- 19839539
TI  - Response to an epidemic of novel H1N1 flu in Pune: need for introspection.

PMID- 19839540
TI  - The Sri Lankan doctors and the challenge for medical leadership.

PMID- 19839541
TI  - Unlinked anonymous HIV testing in population-based surveys in India.

PMID- 19839542
TI  - Everyday ethics: sex determination and ultrasound in Australia.

PMID- 19839543
TI  - Knowledge and attitudes of doctors on medical ethics in a teaching hospital,
      Manipur.
AB  - This study aimed to assess the knowledge of and attitudes to, medical ethics
      among doctors in the Regional Institute of Medical Sciences (RIMS), Imphal,
      Manipur. It also looked at the association between levels of knowledge and
      selected variables. A self-administered structured questionnaire was distributed
      to all doctors working in RIMS, Imphal between September and October 2007. 315 of
      440 (71.6%) doctors contacted, responded. 62.2% of respondents (196) were below
      35 years of age. 22.5% (71) were faculty members. 98.7% (311) had heard of the
      Code of Medical Ethics but only 188 (59.7%) had read it, even in part. 69.2%
      (218) felt that the undergraduate curriculum on medical ethics was not adequate.
      10.5% (33) could describe what medical professionalism meant. Knowledge of
      medical ethics was higher among those who were over 35 years of age, those who
      graduated before 1999 and those having higher educational qualifications. The
      doctors in this survey lacked adequate and detailed knowledge on the code of
      ethics, though most of them had read it once. There is a need to sensitise
      doctors on medical ethics and professionalism.

PMID- 19839544
TI  - From judgement to practice: Section 377 and the medical sector.

PMID- 19839545
TI  - Will the Supreme court's judgement on Section 377 affect mental healthcare for
      LGBT groups?

PMID- 19839546
TI  - Reflections on Gadchiroli.

PMID- 19839547
TI  - Infection control in cataract surgery.

PMID- 19839548
TI  - Maternal mortality in Gujarat.

PMID- 19839549
TI  - A fateful night and a life.

PMID- 19839550
TI  - Addressing the 'third delay' in maternal mortality: need for reform.

PMID- 19839551
TI  - Maternal mortality--the need for a comprehensive systems approach.

PMID- 19839552
TI  - About student research and blanket consent from patients.

PMID- 19839553
TI  - Blanket consent for retrospective studies: patients' obligation.

PMID- 19839555
TI  - Referral for abortion.

PMID- 19839554
TI  - Blanket informed consent for retrospective studies is justified.

PMID- 19839556
TI  - Screening criteria for NICU admissions: decisions require developing trust.

PMID- 19839557
TI  - Clinical trials watch.

PMID- 19839558
TI  - Postural stability in symmetrical gaits.
AB  - In this paper the method of stability analysis of dynamic symmetrical gaits is
      discussed. The problem of dynamic postural equilibrium, taking into account the
      role of compliant feet, is solved. The equilibrium conditions are split between
      the foot attachment points and the points within the foot-end area. The present
      method is useful for motion synthesis, taking into account robot parameters. It
      also helps in the robot foot design. As an illustrative example a four-legged
      diagonal gait is considered. The theoretical results were verified by
      implementing and observing the diagonal gait in four-legged machine with and
      without feet.

PMID- 19839559
TI  - Prototype of minimally invasive hip resurfacing endoprosthesis - bioengineering
      design and manufacturing.
AB  - The resurfacing arthroplasty (RA) has become at present the most developed
      minimally invasive kind of all total arthroplasties, which is a result of the
      progress in biomaterials engineering, biomechanical design and surgical fixation
      methods achieved over the past decade. Despite the raising popularity of RA,
      which undergoes at present its renaissance, it still causes several clinical
      complications. In this paper, we present the most important result our research
      project (4T07C05629), finished in February 2008, which is the prototype of
      original minimally invasive endoprosthesis for total hip resurfacing arthroplasty
      (THRA). We propose the essential innovation in fixation technique of the RA
      endoprosthesis components in trabecular bone by means of the multi-spiked
      connecting scaffold, offering the possibility of totally cementless fixation and
      the physiological blood supply in trabecular bone of femoral head, which is not
      possible in contemporary used cemented RA endoprostheses. Moreover, the femoral
      component is designed to preserve the femoral neck and head blood vessels. The
      prototype of the new kind of hip resurfacing endoprosthesis was CAD-designed in
      the frames of the Rogala's international patent general assumptions [1]-[3],
      optimized on the basis of the preliminary biomechanical tests on the pre
      prototypes, and manufactured in the Selective Laser Melting (SLM) of both CoCrMo
      powder and Ti6Al7Nb powder.

PMID- 19839560
TI  - Parameters of unimplanted and explanted surfaces of Weller endoprosthesis stems.
AB  - 40 samples of stem surfaces of the Weller endoprosthesis of hip joint removed
      because of aseptic loosening were tested. The patients between the ages of 61 and
      87 were examined and the exploitation time of endoprosthesis ranged from 1 to 20
      years. The material analysed was as follows: I group - exploitation 1-3 years (5
      surfaces), II group - exploitation 5-8 years (11 surfaces), III group -
      exploitation 10-14 years (14 surfaces), and IV group - exploitation 16-20 years
      (10 surfaces). Additionally group 0 covered 4 unexploited endoprostheses. We
      analysed the 2-4 mm2 surfaces of the Weller endoprosthesis stems, with the scan
      velocity of 500 mum/s. A decrease in stem amplitude parameters means some
      increase in stem microdisplacements in relation to cement. During the first three
      years, the decrease in the roughness of endoprosthesis surface was larger
      compared with that in further exploitation period. In the case of unexploited
      surfaces of stems, the values of fractal dimension are lower (2.34). During
      exploitation time the Sfd parameter decreases negligibly (2.28-2.24).

PMID- 19839561
TI  - Comparison of microscopic methods for evaluating platelet adhesion to biomaterial
      surfaces.
AB  - Microscopic methods usable for sample surface imaging and subsequent qualitative
      and quantitative evaluation of platelet adhesion to the surface of the
      biomaterial studied were compared. It was shown, making use of the samples of
      medical steel (AISI 316L), that such tools as surface imaging with scanning
      electron microscopy (SEM), glutaraldehyde induced fluorescence technique (GIFT)
      and metallurgical microscopy (MM) are equivalent in evaluating surface platelet
      adhesion. The importance of biological variability of blood samples for a proper
      result assessment and the necessity of using internal standards were also
      considered.

PMID- 19839562
TI  - Hydrodynamic pressure, carrying capacities, friction forces in biobearing gap.
AB  - The present paper deals with the calculations of the pressure distributions,
      carrying capacities and friction forces derivations in a super- thin layer of
      biological synovial fluid inside the slide biobearing gap limited by a spherical,
      conical, cylindrical, parabolic, hyperbolic bone heads. There are also described
      unsteady and random flow conditions of the bio-bearing lubrication with the
      changes of the dynamic viscosity of the synovial fluid in the gap height in
      general.

PMID- 19839563
TI  - The effect of substrate roughness on the surface structure of TiO(2), SiO(2), and
      doped thin films prepared by the sol-gel method.
AB  - Pure and calcium-doped silica and titanium dioxide thin films were prepared by
      the sol-gel method. Two different metallic substrates, i.e. stainless steel
      (316L) and titanium alloy (Ti6Al4V), were used for thin film deposition.
      Physicochemical properties and roughness of the thin films derived were
      investigated using the Raman spectroscopy, X-ray diffraction analysis, scanning
      electron microscopy and Taylor-Hobson's surface analyser. It is suggested that
      the synthesized coatings display physicochemical and surface properties suitable
      for materials used for implant.

PMID- 19839564
TI  - Multiscale FEM model of artificial heart chamber composed of nanocoatings.
AB  - The purpose of the present work was to construct the multiscale FEM model of
      artificial heart chamber composed of nanocoatings. This goal is reached by the
      development of the FEM macromodel of artificial blood chamber using the
      commercial code and by the creation of the micromodel based on our own FEM code.
      The latter uses strain state obtained after loading in macromodel. The loci of
      failure initiation in the material of chamber were precisely determined and these
      results are used as an input data for the new micromodel.

PMID- 19839565
TI  - Interpretive software conversion following changes of patient status and
      diagnostic goals.
AB  - This paper presents selected issues concerning the on-the-run conversion of ECG
      interpretive software following the changes of the patient status and diagnostic
      goals. The adaptation of diagnostic procedure, common in human action, but still
      absent in computerized processing, raises the necessity of including the
      additional medical knowledge in the feedback loop controlling the diagnostic
      process. Considering this knowledge in the form of complementary data attributes
      and the use of modern information processing and digital communication techniques
      opens up the opportunity to simulate a continuous presence of cardiology expert
      accompanying the patient in motion. At the same time, the software does not
      assume the exclusive correctness of the automated diagnosis and provides a human
      expert with verification tools at all stages of signal processing. The portable
      remote recorder was designed and prototyped in our laboratory allowing various
      approaches to automatic software adaptation to be tested.

PMID- 19839566
TI  - Self-assembly of symmetric diblock copolymers in planar slits with and without
      nanopatterns: insight from dissipative particle dynamics simulations.
AB  - We present a dissipative particle dynamics simulation study on the formation of
      nanostructures of symmetric diblock copolymers confined between planar surfaces
      with and without nanopatterns. The nanopatterned surface is mimicked by
      alternating portions of the surface that interact differently with the diblock
      copolymers. The formation of the diblock-copolymer nanostructures confined
      between the planar surfaces is investigated and characterized by varying the
      separation width and the strength of the interaction between the surfaces and the
      diblock copolymers. For surfaces with nanopatterns, we also vary both the mutual
      area and location of the nanopatterns, where we consider nanopatterns on the
      opposing surfaces that are vertically (a) aligned, (b) staggered, and (c)
      partially staggered. In the case of planar slits without nanopatterns, we observe
      the formation of perpendicular and parallel lamellar phases with different
      numbers of lamellae. In addition, the symmetric diblock copolymers self-assemble
      into adsorbed layer and adsorbed layer-parallel lamellar phases and a mixed
      lamellar phase when the opposing surfaces of the planar slits are modeled by
      different types of wall beads. In the case of nanopatterned planar slits, we
      observe novel nanostructures and attempt to rationalize the diblock copolymer
      self-assembly on the basis of the behavior that we observed in the planar slits
      without nanopatterns. In particular, we investigate the applicability of
      predicting the structures formed in the nanopatterned slits by a superposition of
      the observed structures in slits without nanopatterns.

PMID- 19839567
TI  - An efficient protocol for alcohol protection under solvent- and catalyst-free
      conditions.
AB  - A simple and highly efficient protocol for pivaloylation of alcohols without
      using a catalyst under solvent-free conditions has been developed. The key
      advantages of the reaction are short reaction time, high yields, simple workup,
      and no need for further purification. Selectivity was observed between primary
      alcohols vs. secondary alcohols and aliphatic alcohols vs. aromatic alcohols. The
      accentuated and relevant phenomenon of this method that we observed is in one-pot
      conversion of TBS protection into Piv protection of the hydroxyl group.

PMID- 19839568
TI  - Tandem surface microfluidic lithography and activation to generate patch pattern
      biospecific ligand and cell arrays.
AB  - We report a rapid, inexpensive, and flexible methodology that combines
      microfluidic lithography and oxidative activation to pattern and chemically alter
      selective regions of SAMs on gold for subsequent chemoselective ligand
      immobilization. We demonstrate that PCC, a mild oxidant, can be used to convert
      hydroxyl-terminated SAMs to aldehydes and decorated with a variety of oxyamine
      containing molecules. This strategy is compatible with cell culture and was
      employed to create a biospecific ligand platform for peptide-mediated, cell
      adhesion arrays. By using a number of different ligands and characterization
      tools, we showed that the generation of both cell patterning and ligand
      microarray patterning can be achieved. SAM formation, activation, ligand
      immobilization, and biospecific cell patterning are characterized by contact
      angle, cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS)
      (Supporting Information), scanning electron microscopy (SEM), and fluorescence
      microscopy.

PMID- 19839569
TI  - Charge-induced self-assembly of 2-dimensional thermosensitive microgel particle
      patterns.
AB  - The self-assembly of charged microgel particles into two-dimensional arrays on
      various substrates have been investigated by depositing the diluted microgel
      dispersion on the substrate and drying at room temperature. Core-shell type
      thermosensitive microgel particles consist of poly(styrene) (PS) core, whereas
      the shell consists of poly(N-isopropylacrylamide) (PNIPA) network cross-linked by
      N,N'-methylenebisacrylamide (BIS). It is found that the electrostatic
      interactions between microgel particles and charged substrate surface play an
      important role for the formation of ordered 2-D pattern. When microgel particles
      are deposited onto the substrate with opposite surface charges, microgels will
      form ordered 2-D arrays with constant distance between particles. When substrate
      with same surface charge as microgel particles was used, the electrostatic
      repulsion between microgel particles and substrate will destroy the ordered
      structure. Moreover, after embedding Au nanoparticles into the thermosensitive
      microgel particles, the microgel-Au composite particles can also assemble into 2
      D arrays on the substrate.

PMID- 19839570
TI  - Molecular origin of enhanced strength in the monofilament of syndiotactic
      polypropylene because of annealing: a micro-FTIR study.
AB  - The conformational and polymorphic transformations in the melt-spun monofilament
      of syndiotactic polypropylene upon annealing and subsequent stretching have been
      first explored by micro-FTIR studies. The results indicate that annealing of as
      spun monofilament gives rise to an unusual increase in the molecular orientation
      of helical conformations in both amorphous phase and ordered crystals as a result
      of structural transitions of transplanar conformations to helical ones as well as
      mesophase to ordered crystals. The increased molecular orientation in the
      annealed monofilament is mainly responsible for the enhanced strength during
      stretching. Furthermore, high stress exerted by the molecular chains of annealed
      monofilament is confirmed by the significant structural transitions opposite to
      that induced by annealing.

PMID- 19839571
TI  - Stereoselective synthesis of erythronolide A via nitrile oxide cycloadditions and
      related studies.
AB  - An expeditious synthesis of erythronolide A is documented. Key steps of the
      approach include two magnesium-mediated nitrile oxide cycloadditions, a chelation
      controlled Grignard reaction, and a Sharpless asymmetric dihydroxylation.

PMID- 19839572
TI  - Polymerase chain reaction and immunoassay--matrix assisted laser desorption mass
      spectrometry using tag-mass technology: new tools to break down quantification
      limits and multiplexes.
AB  - We present a new development of the Tag-Mass concept based on a photocleavable
      linker with tagged molecules for polymerase chain reaction (PCR) and enzyme
      linked immunosorbent assay (ELISA) quantification coupled to mass spectrometry.
      PCR-MS and immunosorbent assay-MS with tagged oligonucleotides, bases, and
      antibodies will allow the acquisition of multiplexed information from genomic,
      transcriptomic, and proteomic experiments. This is a novel application of Tag
      Mass from tissue imaging to fluid quantification and will open doors to several
      clinical applications ranging from biomarker-driven gene modulation to use at the
      patient's bedside following treatment.

PMID- 19839573
TI  - Recyclable molecular trapping and SERS detection in silver-loaded agarose gels
      with dynamic hot spots.
AB  - We describe the design and fabrication of composite agarose gels, highly loaded
      with silver nanoparticles. Because the gel can collapse upon drying and recover
      when rehydrated, it can be foreseen as an excellent mechanical molecular trap
      that additionally gives rise to dynamic hot spots as the network volume decreases
      and the silver particles get close to each other, thereby generating the high
      electromagnetic fields that are needed for ultradetection. Additionally, as
      silver nanoparticles are physically trapped inside the polymer network, analytes
      can be washed out by dialysis when immersed in a washing solution, so that
      recycling can be achieved. Finally, the use of SERS for ultradetection of
      dichlorodiphenyl-trichloroethane (DDT) is reported for the first time,
      demonstrating the ability of this novel nanocomposite material to reversibly
      sequester nonconventional SERS analytes.

PMID- 19839574
TI  - Luminescence properties of lanthanide and transition metal ion-doped Ba2LaNbO6:
      detection of MnO6(8-) and CrO6(9-) clusters.
AB  - The as-prepared double-perovskite Ba(2)LaNbO(6) (space group I2/m at ambient
      temperatures) exhibited an unexpected well-resolved red luminescence, which was
      found to arise from parts-per-million impurity of Mn(4+). The ions Mn(4+) or
      Cr(3+) doped into this host are situated at Nb(5+) sites with slightly distorted
      octahedral symmetry, with the distortion greater for the case of greater charge
      mismatch. The Stokes luminescence spectra of the dopant ions comprise nu(3),
      nu(4), and nu(6) moiety mode vibronic origins, and the high vibrational frequency
      ratio nu(4)/nu(3) signals the stiffness of the O-M-O (M = Mn, Cr) angle in the
      double perovskite. The site symmetry at the La(3+) site of lanthanide ions doped
      into Ba(2)LaNbO(6) comprises a 2-fold axis at most. All dopant ions exhibit
      concentration quenching in this lattice.

PMID- 19839575
TI  - High energy resolution X-ray absorption spectroscopy of environmentally relevant
      lead(II) compounds.
AB  - The determination of the chemical environment of Pb in natural samples is a
      challenge of great importance in environmental and health physics. We report a
      high energy resolution fluorescence detection (HERFD) X-ray absorption near-edge
      spectroscopy (XANES) study at the Pb L(3) and L(1) absorption edges to determine
      the chemical environment of Pb in a series of model and environmentally relevant
      compounds. HERFD spectroscopy can reveal increased spectral detail due to an
      apparent reduction in the core hole lifetime broadening. HERFD spectra of model
      Pb(II) compounds were compared to FEFF 8.4 multiple scattering calculations with
      reduced peak broadening parameters, and density of state (DOS) simulations, to
      determine the origins of the spectral features. A pre-edge in the L(3) XANES is
      revealed which is shown to arise from hybridization between the Pb p and d
      states. HERFD spectra of Pb(II)-containing environmentally relevant solutions
      were compared to model spectra and calculations. The results presented in this
      paper show that the chemical environment of Pb can be identified from spectral
      features resolved in HERFD spectroscopy at the Pb L(3) edge. The technique
      provides information that is complementary to conventional extended X-ray
      absorption fine structure (EXAFS) spectroscopy.

PMID- 19839576
TI  - Luminescent lanthanide helicates self-assembled from ditopic ligands bearing
      phosphonic acid or phosphoester units.
AB  - A series of hexadentate ditopic receptors incorporating benzimidazole moieties
      have been designed, which are fitted with phosphonic acid or phosphoethylester
      coordinating units. In addition, poly(oxyethylene) pendants have been introduced
      on the benzimidazole backbone of two ligands to increase water solubility. The
      ligands self-assemble with lanthanide ions under stoichiometric conditions,
      yielding triple-stranded homobimetallic helicates, as ascertained by mass
      spectrometry and UV-visible titrations. The helicates display large thermodynamic
      stability, for example, log beta(23) approximately 21-24 for all the Eu(III)
      complexes. Photophysical measurements reveal sensitization of the metal-centered
      luminescence in the europium and terbium complexes, which is modulated by the
      nature of the ligand. Hydration numbers determined by the lifetime method are
      essentially zero. The Eu((5)D(0)) lifetimes are long and reach values up to 3.2
      ms, while quantum yields as high as 25% are obtained in water at pH 7.4. Back
      transfer limits the sensitization efficiency for Tb(III) luminescence, and both
      lifetimes and quantum yields are much smaller. The properties of the helicates
      are discussed with respect to those self-assembled from ligands bearing
      carboxylate coordinating units.

PMID- 19839577
TI  - Calcium complexation by corticosteroids.
AB  - Cortisone and hydrocortisone form calcium complexes of 2:1 steroid/Ca(2+)
      stoichiometry in solution, with formation constants of 201 +/- 1.7 and 184 +/-
      1.7 M(-2), respectively-roughly half the value seen for a simple aromatic alpha
      hydroxy ketone, phenacyl alcohol (341 +/- 10.0 M(-2)). X-ray crystallographic
      analysis demonstrates maintenance of this 2:1 stoichiometry in the solid state
      for the phenacyl alcohol and cortisone complexes, while the hydrocortisone
      complex crystallizes with a 1:1 stoichiometry in the form of linear chains, with
      the alpha-hydroxy ketone ligand and C(3) (A-ring) carbonyl groups binding two
      different calcium ions. In each complex, both in solution and in the solid state,
      the alpha-hydroxy ketone moiety serves as a bidentate chelator for calcium.
      Extensive hydrogen-bonded networks are present in each structure, linking various
      hydroxyl groups, coordinated and noncoordinated hydrate molecules, and the
      chloride counterions, in essence representing supramolecular complexation of the
      hydrated chloride anion.

PMID- 19839578
TI  - Facile route to nitrides: transformation from single element to binary and
      ternary nitrides at moderate temperature through a new modified solid-state
      metathesis.
AB  - In this article, we report a new modified solid-state metathesis pathway to
      synthesize nitrides using Li(3)N as a nitrification reagent to transform single
      element to nitrides. In this process, not only binary (including mono- and
      multinitrides) but also ternary nitrides can be approached by varying the molar
      ratio of Li(3)N to a single element. A possible two-step reaction mechanism for
      Li(3)N and single elements was proposed. This study provides a promising route to
      meet the increasing demand in energy savings and environmental protection for
      materials synthesis.

PMID- 19839579
TI  - Electro-Fenton process and related electrochemical technologies based on Fenton's
      reaction chemistry.

PMID- 19839580
TI  - Dynamic nanoinscribing for continuous and seamless metal and polymer
      nanogratings.
AB  - Nanoscale grating structure can be utilized in many practical applications in
      optics, flat-panel displays, and biosensors. We present a dynamic nanoinscribing
      (DNI) technique for directly creating large-area, truly continuous nanograting
      patterns in a variety of metal or polymer materials with feature size down to sub
      50 nm and at very high speed (10 cm/sec). DNI is carried out under either ambient
      temperature or with a brief heating time on the order of 10 micros, which
      minimizes damage on UV or thermosensitive functional materials. We also
      demonstrated future applications of the DNI process into the simple, one-step
      fabrication of split-ring resonator (SRR) structures for negative index
      materials.

PMID- 19839581
TI  - The abnormal hydrolysis of 7-phosphanorbornenium salts: a case of phosphonium
      phosphenium equivalence.
AB  - The hydrolysis of a phosphanorbornenium triflate gives the expected tertiary
      phosphine oxide by cleavage of one P-C bond of the bridge in the presence of
      triethylamine but affords the secondary phosphine oxide by cleavage of the two P
      C bonds of the bridge in the presence of alpha-picoline.

PMID- 19839582
TI  - An antibody-recruiting small molecule that targets HIV gp120.
AB  - HIV/AIDS is a global pandemic for which new treatment strategies are desperately
      needed. We have designed a novel small molecule, designated as ARM-H, that has
      the potential to interfere with HIV survival through two mechanisms: (1) by
      recruiting antibodies to gp120-expressing virus particles and infected human
      cells, thus enhancing their uptake and destruction by the human immune system,
      and (2) by binding the viral glycoprotein gp120, inhibiting its interaction with
      the human protein CD4 and preventing virus entry. Here we demonstrate that ARM-H
      is capable of simultaneously binding gp120, a component of the Env surface viral
      glycoprotein (found on the surface of both HIV and virus-infected cells) and anti
      2,4-dinitrophenyl antibodies (already present in the human bloodstream). The
      ternary complex formed between the antibody, ARM-H, and gp120 is immunologically
      active and leads to the complement-mediated destruction of Env-expressing cells.
      Furthermore, ARM-H prevents virus entry into human T-cells and should therefore
      be capable of inhibiting virus replication through two mutually reinforcing
      mechanisms (inhibition of virus entry and antibody-mediated killing). These
      studies demonstrate the viable anti-HIV activity of antibody-recruiting small
      molecules and have the potential to initiate novel paradigms in HIV treatment.

PMID- 19839583
TI  - Profile of plasma and urine metabolites after the intake of almond [Prunus dulcis
      (Mill.) D.A. Webb] polyphenols in humans.
AB  - Nut skins are considered to be a rich source of polyphenols and may be partially
      responsible for the numerous health effects associated with nut consumption.
      However, more bioavailability studies of nut skin polyphenols are needed to
      understand the health effects derived from nut consumption. The aim of the
      present study was to determine the profiles of both phase II and microbial
      derived phenolic metabolites in plasma and urine samples before and after the
      intake of almond skin polyphenols by healthy human subjects (n = 2). Glucuronide,
      O-methyl glucuronide, sulfate, and O-methyl sulfate derivatives of (epi)catechin,
      as well as the glucuronide conjugates of naringenin and glucuronide and sulfate
      conjugates of isorhamnetin, were detected in plasma and urine samples after
      consumption of almond skin polyphenols. The main microbial-derived metabolites of
      flavanols, such as 5-(dihydroxyphenyl)-gamma-valerolactone and 5
      (hydroxymethoxyphenyl)-gamma-valerolactone, were also detected in their
      glucuronide and sulfate forms. In addition, numerous metabolites derived from
      further microbial degradation of hydroxyphenylvalerolactones, including
      hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic, and
      hydroxyhippuric acids, registered major changes in urine after the consumption of
      almond skin polyphenols. The urinary excretion of these microbial metabolites was
      estimated to account for a larger proportion of the total polyphenol ingested
      than phase II metabolites of (epi)catechin, indicating the important role of
      intestinal bacteria in the metabolism of highly polymerized almond skin
      polyphenols. To the authors' knowledge this study constitutes the most complete
      report of the absorption of almond skin polyphenols in humans.

PMID- 19839585
TI  - Synthesis of 4- and 6-azaindoles via the Fischer reaction.
AB  - Contrary to the common idea that Fischer indole cyclization often cannot be
      effectively applied to the synthesis of the corresponding azaindoles, we show
      that this approach can be actually very efficient for the formation of 4- and 6
      azaindoles bearing an electron-donating group on the starting pyridylhydrazines.
      Two 4-azaindole natural product analogues were synthesized in a few steps and
      very good overall yields.

PMID- 19839586
TI  - Migration and diffusion of diphenylbutadiene from packages into foods.
AB  - Monitoring of exposure to chemicals from food contact materials is a subject of
      increasing importance. The concentration of the chemicals and their migration
      levels, as well as food consumption and packaging usage data, are required to
      enable calculation of the degree of such exposure. The present study investigated
      the migration kinetics of diphenylbutadiene (DPBD) from packages into flour,
      rice, honey, milk powder and toast. Migration was not always negligible, except
      in honey and skimmed milk powder. Experiments carried out with starch alone
      enabled us to conclude that diffusion of migrants occurred through starch and
      fat. Key diffusion parameters were determined (diffusion coefficient and
      partition coefficient) based on Fick's second equation. The following diffusion
      coefficients were obtained at 25 degrees C: 2.7 x 10(-10), 3.4 x 10(-11), 3.2 x
      10(-10), 8.4 x 10(-11), 8.1 x 10(-11) cm(2) s(-1), for wheat flour, rice, milk
      powder and toast, with 4 and 21% fat, respectively. A very good fit between
      experimental and predicted data was achieved. The data obtained in the present
      study confirm the validity of the mathematical model for predicting migration
      from Food Contact Materials (FCM) into foods.

PMID- 19839584
TI  - Selective estrogen receptor modulator delivery of quinone warheads to DNA
      triggering apoptosis in breast cancer cells.
AB  - Estrogen exposure is a risk factor for breast cancer, and estrogen oxidative
      metabolites have been implicated in chemical carcinogenesis. Oxidation of the
      catechol metabolite of estrone (4-OHE) and the beta-naphthohydroquinone
      metabolite of equilenin (4-OHEN) gives o-quinones that produce ROS and damage DNA
      by adduction and oxidation. To differentiate hormonal and chemical carcinogensis
      pathways in estrogen receptor positive ER(+) cells, catechol or beta
      naphthohydroquinone warheads were conjugated to the selective estrogen receptor
      modulator (SERM) desmethylarzoxifene (DMA). ER binding was retained in the DMA
      conjugates; both were antiestrogens with submicromolar potency in mammary and
      endometrial cells. Cytotoxicity, apoptosis, and caspase-3/7 activation were
      compared in ER(+) and ER(-)MDA-MB-231 cells, and production of ROS was detected
      using a fluorescent reporter. Comparison was made to DMA, isolated warheads, and
      a DMA-mustard. Conjugation of warheads to DMA increased cytotoxicity accompanied
      by induction of apoptosis and activation of caspase-3/7. Activation of caspase
      3/7, induction of apoptosis, and cytotoxicity were all increased significantly in
      ER(+) cells for the DMA conjugates. ROS production was localized in the nucleus
      for conjugates in ER(+) cells. Observations are compatible with beta
      naphthohydroquinone and catechol groups being concentrated in the nucleus by ER
      binding, where oxidation and ROS production result, concomitant with caspase
      dependent apoptosis. The results suggest that DNA damage induced by catechol
      estrogen metabolites can be amplified in ER(+) cells independent of hormonal
      activity. The novel conjugation of quinone warheads to an ER-targeting SERM gives
      ER-dependent, enhanced apoptosis in mammary cancer cells of potential application
      in cancer therapy.

PMID- 19839587
TI  - Guanosine + OH radical reaction in aqueous solution: a reinterpretation of the UV
      vis data based on thermodynamic and kinetic calculations.
AB  - Thermodynamic and kinetic calculations have been used to reinterpret the UV-vis
      data related to the OH radical oxidation of guanosine. The main channel of
      reaction (70-75%) is proposed to be the formation of a guanosine radical cation
      followed by deprotonation. It accounts for both the absorbance decay at
      approximately 620 nm and the build-up at approximately 300 nm. A secondary
      channel yielding the G8OH adduct was found to contribute to the overall reaction
      by 12% at least.

PMID- 19839588
TI  - Characterization and antitumor effect of a novel polysaccharide from Grifola
      frondosa.
AB  - A novel polysaccharide, MZF, with a molecular mass of 23 kDa was isolated from
      Grifola frondosa . Results from methylation and (1)H NMR led to the conclusion
      that MZF is a heteropolysaccharide consisting of -->6)-alpha-D-Galp-(1-->
      (36.2%), -->3)-alpha-L-Fucp-(1--> (14.5%), -->6)-alpha-D-Manp-(1--> (9.4%), -->3)
      beta-D-Glcp-(1--> (10.1%), alpha-D-Manp-(1--> (23.2%), and -->3,6)-beta-D-Glcp-(1
      -> (6.5%). Although MZF did not affect the proliferation of colon-26 cells in
      vitro, it significantly inhibited tumor growth in BALB/cA mice inoculated with
      colon-26 cancer cells. Moreover, MZF significantly induced the proliferation of
      splenocytes and peritoneal macrophages. The mRNA expression of IL-12p40, IL-2 and
      IFN-gamma were increased significantly in MZF-treated spleen. Furthermore, MZF
      augmented the percentage of IFN-gamma-producing cells in both splenic CD4(+) and
      CD8(+) T cells and tumor infiltrating CD4(+) and CD8(+) T cells and enhanced the
      cytotoxic activity of NK cells and CTLs. These results indicate that MZF is a
      novel effective immunomodulator that has antitumor activity associated with
      induced cell-mediated immunity.

PMID- 19839589
TI  - A multiresidue method for the determination of 118 pesticides in vegetable juice
      by gas chromatography-mass spectrometry and liquid chromatography-tandem mass
      spectrometry.
AB  - An analytical method has been developed for measuring 118 pesticides in vegetable
      juice. The extraction of pesticides was carried out based on dispersive solid
      phase extraction, and determination was performed using gas chromatography with
      mass spectrometric detection (GC-MS-SIM) and liquid chromatography electrospray
      ionization tandem mass spectrometry (LC/ESI-MS/MS). Pesticides were confirmed by
      their retention time and their quantification and identification ions by GC-MS
      SIM or multiple reaction monitoring of two fragment ions by LC/ESI-MS/MS,
      respectively. Spiking experiments from 10 to 120 microg/kg were carried out to
      determine the recovery, precision, and limit of quantification (LOQ) of the
      method. The overall recoveries of all pesticides were between 77 and 114% with
      relative standard deviations lower than 14%. The LOQ for most compounds was below
      5 microg/kg. The proposed method was applied successfully for the residue
      determination of the 118 pesticides in commercial vegetable juice samples.

PMID- 19839590
TI  - Comprehensive investigation of the energetics of pyrimidine nucleoside formation
      in a model prebiotic reaction.
AB  - The problem of beta-nucleoside formation under prebiotic conditions represents
      one of the most significant challenges to the "RNA world" hypothesis. The
      possibility exists that alternative bases may have come before the contemporary
      bases (i.e., A, G, C, and U), including bases that more readily form nucleosides.
      We previously reported the first successful synthesis of a pyrimidine nucleoside
      from a free base and a nonactivated sugar in a plausible prebiotic reaction. Here
      we present a detailed computational study on the reaction at the density
      functional theory (DFT) level. The catalytic role of a Mg(2+) ion on the reaction
      mechanism is also investigated. Our calculations demonstrate that a Mg(2+) ion,
      serving as a Lewis acid, can afford the necessary stabilization to the base and
      leaving water molecule during glycoside bond formation. The solvent effect is
      considered by the Onsager solvation model and also by an extended model with the
      addition of explicit water molecules within the SCRF solvation model. In
      addition, predictions regarding the formation of nucleosides from other
      pyrimidine bases are also addressed, providing valuable insights into what
      chemical features of the bases facilitate glycoside formation in drying-heating
      reactions.

PMID- 19839591
TI  - Alkynylated aceno[2,1,3]thiadiazoles.
AB  - Enlarged acenothiadiazoles, which are easily prepared, display attractive optical
      and electrochemical properties. The annulation of thiadiazole to anthracene gives
      a stable material with optical properties similar to those of substituted
      pentacenes.

PMID- 19839592
TI  - Synthesis and biological evaluation of 2-alkynyl-N6-methyl-5'-N
      methylcarboxamidoadenosine derivatives as potent and highly selective agonists
      for the human adenosine A3 receptor.
AB  - A new series of 2-aralkynyl-N(6)-methyl-MECAs 10-13 were synthesized and
      evaluated in radioligand binding studies and in a new Eu-GTP functional assay
      that provides a powerful alternative to radioisotope use. The new compounds
      possess high affinity and selectivity for the AA(3)R with N(6)-methyl-2
      phenylethynylMECA (10) showing a subnanomolar affinity and about 100000-fold
      selectivity vs AA(1)R and AA(2A)R. Furthermore, the new nucleosides showed to be
      full agonists, the N(6)-methyl-2-(2-pyridinyl)ethynylMECA (13) being the most
      potent in the series.

PMID- 19839593
TI  - Tea catechins inhibit hepatocyte growth factor receptor (MET kinase) activity in
      human colon cancer cells: kinetic and molecular docking studies.
AB  - Most cancer deaths result from spread of the primary tumor to distant sites
      (metastasis). MET is an important protein for metastasis in multiple tumor types.
      Here we report on the ability of tea catechins to suppress MET activation in
      human colon cancer cells and propose a mechanism by which they might compete for
      the kinase domain of the MET protein.

PMID- 19839594
TI  - Multiple reaction monitoring cubed for protein quantification at the low
      nanogram/milliliter level in nondepleted human serum.
AB  - Mass spectrometry-based strategies for the quantification of low-abundance
      putative protein biomarkers in human blood currently require extensive sample
      fractionation steps which hamper their implementation in a routine and robust way
      across clinical laboratories. We demonstrate that a technique using MS(3)
      reconstructed chromatograms on a signature of secondary ions issued from a
      trapped primary product ion, termed multiple reaction monitoring cubed (MRM(3)),
      enables targeting protein biomarkers in the low nanogram/milliliter range in
      nondepleted human serum. The simple two-step workflow is based on a trypsin
      proteolysis of whole serum (100 microL) followed by enrichment of targeted
      proteotypic peptides on a solid phase extraction column using mixed-cation
      exchange resin. MRM(3)'s fidelity of peak detection extends the dynamic range and
      limit of quantitation (LOQ) of protein biomarkers to the low nanogram/milliliter
      range, corresponding to a concentration that is 10(6)-fold lower than the
      concentration of the most abundant proteins in serum. The power of the MRM(3)
      method is illustrated by the assay of prostate specific antigen in nondepleted
      human sera of patients. The results correlate well with the established method
      for determining PSA levels in serum, i.e., enzyme-linked immunosorbent assay
      (ELISA) tests.

PMID- 19839595
TI  - Software tool for researching annotations of proteins: open-source protein
      annotation software with data visualization.
AB  - In order that biological meaning may be derived and testable hypotheses may be
      built from proteomics experiments, assignments of proteins identified by mass
      spectrometry or other techniques must be supplemented with additional notation,
      such as information on known protein functions, protein-protein interactions, or
      biological pathway associations. Collecting, organizing, and interpreting this
      data often requires the input of experts in the biological field of study, in
      addition to the time-consuming search for and compilation of information from
      online protein databases. Furthermore, visualizing this bulk of information can
      be challenging due to the limited availability of easy-to-use and freely
      available tools for this process. In response to these constraints, we have
      undertaken the design of software to automate annotation and visualization of
      proteomics data in order to accelerate the pace of research. Here we present the
      Software Tool for Researching Annotations of Proteins (STRAP), a user-friendly,
      open-source C# application. STRAP automatically obtains gene ontology (GO) terms
      associated with proteins in a proteomics results ID list using the freely
      accessible UniProtKB and EBI GOA databases. Summarized in an easy-to-navigate
      tabular format, STRAP results include meta-information on the protein in addition
      to complementary GO terminology. Additionally, this information can be edited by
      the user so that in-house expertise on particular proteins may be integrated into
      the larger data set. STRAP provides a sortable tabular view for all terms, as
      well as graphical representations of GO-term association data in pie charts
      (biological process, cellular component, and molecular function) and bar charts
      (cross comparison of sample sets) to aid in the interpretation of large data sets
      and differential analyses experiments. Furthermore, proteins of interest may be
      exported as a unique FASTA-formatted file to allow for customizable re-searching
      of mass spectrometry data, and gene names corresponding to the proteins in the
      lists may be encoded in the Gaggle microformat for further characterization,
      including pathway analysis. STRAP, a tutorial, and the C# source code are freely
      available from http://cpctools.sourceforge.net.

PMID- 19839596
TI  - Colorimetric, high-throughput assay for screening Angiotensin I-converting enzyme
      inhibitors.
AB  - Angiotensin I-converting enzyme (ACE) plays a pivotal role in blood pressure
      regulation. A colorimetric assay to measure hippuric acid (HA) was transformed
      into a rapid ACE assay wherein the released HA from the substrate hippuryl
      histidyl-leucine (HHL) is mixed with pyridine and benzene sulfonyl chloride. The
      resulting yellow color with a lambda(max) at 410 nm is directly proportional to
      the released HA. The limit of detection and limit of quantitation were 1.46 x 10(
      7) and 4.43 x 10(-7) M HA. ACE activities of different tissues using this method
      were comparable to the standard high-performance liquid chromatography (HPLC)
      method. Kinetic studies showed a K(m) of 30.8 +/- 0.1 x 10(-6) M for HHL and
      V(max) of 1.3 +/- 0.01 x 10(-6) mol/min for porcine lung ACE. This assay coupled
      with captopril and lisinopril showed IC(50) values of 1.1 +/- 0.05 x 10(-9) and
      2.5 +/- 0.03 x 10(-9) M, respectively. A 96-well microplate format of this method
      was used to screen the ACE inhibitory potential of peptides fractionated from an
      enzymatic hydrolysate of arachin. The precision, accuracy, reproducibility, and
      excellent correlation demonstrated between the colorimetric and the often-used
      HPLC method renders this extraction-free method a powerful tool for high
      throughput screening of ACE inhibitors.

PMID- 19839597
TI  - Biomonitoring of organophosphorus agent exposure by reactivation of
      cholinesterase enzyme based on carbon nanotube-enhanced flow-injection
      amperometric detection.
AB  - A portable, rapid, and sensitive assessment of subclinical organophosphorus (OP)
      agent exposure based on reactivation of cholinesterase (ChE) from OP-inhibited
      ChE using rat saliva (in vitro) was developed using an electrochemical sensor
      coupled with a microflow-injection system. The sensor was based on a carbon
      nanotube (CNT)-modified screen printed carbon electrode (SPE), which was
      integrated into a flow cell. Because of the extent of interindividual ChE
      activity variability, ChE biomonitoring often requires an initial baseline
      determination (noninhibited) of enzyme activity which is then directly compared
      with activity after OP exposure. This manuscript describes an alternative
      strategy where reactivation of the phosphorylated enzyme was exploited to enable
      measurement of both inhibited and baseline ChE activity (after reactivation by an
      oxime, i.e., pralidoxime iodide) in the same sample. The use of CNT makes the
      electrochemical detection of the products from enzymatic reactions more feasible
      with extremely high sensitivity (5% ChE inhibition) and selectivity. Paraoxon was
      selected as a model OP compound for in vitro inhibition studies. Some
      experimental parameters, e.g., inhibition and reactivation time, have been
      optimized such that 92-95% of ChE reactivation can be achieved over a broad range
      of ChE inhibition (5-94%) with paraoxon. The extent of enzyme inhibition using
      this electrochemical sensor correlates well with conventional enzyme activity
      measurements. On the basis of the double determinations of enzyme activity, this
      flow-injection device has been successfully used to detect paraoxon inhibition
      efficiency in saliva samples (95% of ChE activity is due to
      butyrylcholinesterase), which demonstrated its promise as a sensitive monitor of
      OP exposure in biological fluids. Since it excludes inter- or intraindividual
      variation in the normal levels of ChE, this new CNT-based electrochemical sensor
      thus provides a sensitive and quantitative tool for point-of-care assessment and
      noninvasive biomonitoring of the exposure to OP pesticides and chemical nerve
      agents.

PMID- 19839598
TI  - Poly[hydroxyethyl acrylate-co-poly(ethylene glycol) diacrylate] monolithic column
      for efficient hydrophobic interaction chromatography of proteins.
AB  - Rigid poly[hydroxyethyl acrylate-co-poly(ethylene glycol) diacrylate] monoliths
      were synthesized inside 75 mum i.d. capillaries by one-step UV-initiated
      copolymerization using methanol and ethyl ether as porogens. The optimized
      monolithic column was evaluated for hydrophobic interaction chromatography (HIC)
      of standard proteins. Six proteins were separated within 20 min with high
      resolution using a 20 min elution gradient, resulting in a peak capacity of 54.
      The effect of gradient rate and initial salt concentration on the retention of
      proteins were investigated. Mass recovery was found to be greater than 96%,
      indicating the biocompatibility of this monolith. The monolith was mechanically
      stable and showed nearly no swelling or shrinking in different polarity solvents.
      The preparation of this in situ polymerized acrylate monolithic column was highly
      reproducible. The run-to-run and column-to-column reproducibilities were less
      than 2.0% relative standard deviation (RSD) on the basis of the retention times
      of protein standards. The performance of this monolithic column for HIC was
      comparable or superior to the performance of columns packed with small particles.

PMID- 19839599
TI  - Pyridinium lipids with the dodecaborate cluster as polar headgroup: synthesis,
      characterization of the physical-chemical behavior, and toxicity in cell culture.
AB  - We have prepared nine new dodecaborate cluster lipids with potential use in boron
      neutron capture therapy of tumors. This new generation of boron lipids is only
      singly negatively charged and consists of a pyridinium core with C(12), C(14),
      and C(16) chains as lipid backbone, connected through the nitrogen atom via a
      butylene, pentylene, or ethyleneoxyethylene linker to the oxygen atom on the
      dodecaborate cluster as headgroup. The lipids were obtained by nucleophilic
      attack of 4-(bisalkylmethyl)pyridine on the tetrahydrofurane, the dioxane, and a
      newly prepared tetrahydropyrane derivative, respectively, of closo-dodecaborate.
      All of these boron lipids are able to form closed vesicles in addition to some
      bilayers in the pure state and in the presence of helper lipids. The thermotropic
      behavior was found to be increasingly complex and polymorphic with increasing
      alkyl chain length. Except for two lipids, all lipids have low in vitro toxicity,
      and longer alkyl chains lead to a significant decrease in toxicity. The choice of
      the linker plays no major role with respect to their ability to form liposomes
      and their thermotropic properties, but the toxicity is influenced by the linkers
      in the case of short alkyl chains.

PMID- 19839601
TI  - Calmodulin is a nonessential activator of secretory phospholipase A(2).
AB  - Ammodytoxins are presynaptically neurotoxic snake venom group IIA secreted
      phospholipase A(2) enzymes that interact specifically with calmodulin in the
      cytosol of nerve cells. We show that calmodulin behaves as an activator of
      ammodytoxin under both nonreducing and reducing (cytosol-like) conditions by
      stimulating its enzymatic activity up to 21-fold. Kinetic analysis, using a
      general modifier mechanism, and surface plasmon resonance measurements reveal
      that calmodulin influences both the catalytic and the vesicle binding properties
      of the enzyme without affecting its calcium binding properties. The equilibrium
      dissociation constant of the ammodytoxin-calmodulin complex under cytosol-like
      conditions is in the low nanomolar range (3 nM), while under nonreducing
      conditions, the binding affinity is in the subnanomolar range (0.07-0.18 nM).
      Upon exposure to cytosol-like conditions, ammodytoxin undergoes a slow hysteretic
      transition to a less active state. Calmodulin stabilizes the conformation of
      ammodytoxin and thereby restores its activity. These results provide insights
      into the neurotoxic action of ammodytoxins and the mechanisms involved in the
      regulation of secreted phospholipase A(2) activity within the cytosol.

PMID- 19839600
TI  - Hypochlorous acid reacts with the N-terminal methionines of proteins to give
      dehydromethionine, a potential biomarker for neutrophil-induced oxidative stress.
AB  - Electrophilic halogenating agents, including hypohalous acids and haloamines,
      oxidize free methionine and the N-terminal methionines of peptides and proteins
      (e.g., Met-1 of anti-inflammatory peptide 1 and ubiquitin) to produce
      dehydromethionine (a five-membered isothiazolidinium heterocycle). Amide
      derivatives of methionine are oxidized to the corresponding sulfoxide derivatives
      under the same reaction conditions (e.g., Met-3 of anti-inflammatory peptide 1).
      Other biological oxidants, including hydrogen peroxide and peroxynitrite, also
      produce only the corresponding sulfoxides. Hypothiocyanite does not react with
      methionine residues. We suggest that dehydromethionine may be a useful biomarker
      for the myeloperoxidase-induced oxidative stress associated with many
      inflammatory diseases.

PMID- 19839602
TI  - Drying of colloidal suspensions and polymer solutions near the contact line:
      deposit thickness at low capillary number.
AB  - Drying experiments with a receding contact line have been performed with silica
      colloidal suspensions and polyacrylamide (PAAm) polymer solutions. The
      experimental setup allows to control the receding movement of the contact line
      and the evaporation flux separately. Deposit thickness as a function of these two
      control parameters has been investigated. The different systems exhibit a similar
      behavior: in the regime of very low capillary numbers the deposit thickness
      scaled by the solute volume concentration and the evaporation rate is
      proportional to the inverse of the contact line velocity. Both the scaling
      exponent and the constant (which has the dimension of a length) do not depend on
      the system under study. The observation of this evaporative regime confirms some
      recent results obtained by Le Berre et al. on a very different system
      (phospholipidic molecules) and fully supports their interpretation. Following
      their approach, a simple model based on mass balance accounts for these results.
      This implies that this regime is dominated by the evaporation and that the
      deformation of the meniscus induced by viscous forces does not play any
      significant role. When increasing the velocity, another regime is observed where
      the thickness does not depend significantly on the velocity.

PMID- 19839603
TI  - Controlled integration of polymers into viral capsids.
AB  - In this paper, we describe the controlled incorporation of two synthetic polymers
      with different structures in the cowpea chlorotic mottle virus (CCMV) capsid.
      Poly(ethylene glycol) (PEG) chains have been attached to the amine groups of
      lysine residues on the outer surface of the viral capsid. The functionalization
      of CCMV with PEG chains provoked a slow but irreversible dissociation of the
      virus into PEG-coat protein (CP) subunits, likely due to steric interference
      between the protein-protein subunits as a result of the presence of the PEG
      chains. This thermodynamic instability, however, can be overcome if a second
      polymer, such as polystyrene sulfonate (PSS), is present within the capsid. After
      complete disassembly of the PEG-CCMV conjugates and removal of the viral RNA,
      incubation of the PEG-functionalized coat proteins with PSS resulted in the
      formation of much more robust PSS-CCMV-PEG capsids with a diameter of 18 nm (T =
      1 capsids). These are the first virus-like particles bearing synthetic organic
      polymers both inside and outside the viral capsid, opening a new route to the
      synthesis of biohybrid nanostructured materials based on viruses.

PMID- 19839604
TI  - Structures, ionization equilibria, and tautomerism of 6-oxopurines in solution.
AB  - 6-Oxopurine and its analogues form an important class of biological molecules
      that include nucleobases and their precursors and are substrates of a wide range
      of enzymes. Solution structures of purines have been debated in the literature
      because of the many possible tautomers and protonation states in which they can
      exist in solution. Substitutions on the pyrimidine and imidazole rings alter
      tautomerization and protonation equilibria, and as a consequence, the solution
      compositions and structures of closely related analogues can be significantly
      different. We have obtained resonance Raman spectra of 6-oxopurines:
      hypoxanthine, xanthine, their riboside phosphates, guanine monophosphate in the
      protonated and deprotonated forms with UV excitation at 260 nm. The species
      present in solution under different pH conditions were identified by isotopic
      labeling with deuterium as well as by comparison with extensive density
      functional theoretical calculations. At physiological pH, while N7H and N9H
      tautomeric forms of hypoxanthine exist in equilibrium, in xanthine, the
      additional carbonyl group at C2 shifts the equilibrium in favor of the N7H
      tautomer. The corresponding nucleotide of xanthine, xanthosine monophosphate, on
      the other hand, is in the anionic form (pK(a) 5.5). We find that Raman spectra
      show systematic shifts with change in the protonation state and substitution on
      the ring. In general, deprotonation of the neutral molecule is marked by a
      downshift in the observed Raman wavenumbers, and protonation is accompanied by an
      upshift.

PMID- 19839605
TI  - Betulin-derived compounds as inhibitors of alphavirus replication.
AB  - This paper describes inhibition of Semliki Forest virus (SFV) replication by
      synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical
      modifications were made to OH groups at C-3 and C-28 and to the C-20-C-29 double
      bond. A set of heterocyclic betulin derivatives was also assayed. A free or
      acetylated OH group at C-3 was identified as an important structural contributor
      for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent
      derivative (IC50 value 9.1 microM). Betulinic acid (13), 28-O
      tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown
      to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 microM,
      respectively. The latter three compounds also had significant synergistic effects
      against SFV when combined with 3'-amino-3'-deoxyadenosine. In contrast to
      previous work on other viruses, the antiviral activity of 13 was mapped to take
      place in virus replication phase. The efficacy was also shown to be independent
      of external guanosine supplementation.

PMID- 19839606
TI  - Palmyramide A, a cyclic depsipeptide from a Palmyra Atoll collection of the
      marine cyanobacterium Lyngbya majuscula.
AB  - Bioassay-guided fractionation of the extract of a consortium of a marine
      cyanobacterium and a red alga (Rhodophyta) led to the discovery of a novel
      compound, palmyramide A, along with the known compounds curacin D and malyngamide
      C. The planar structure of palmyramide A was determined by one- and two
      dimensional NMR studies and mass spectrometry. Palmyramide A is a cyclic
      depsipeptide that features an unusual arrangement of three amino acids and three
      hydroxy acids; one of the hydroxy acids is the rare 2,2-dimethyl-3
      hydroxyhexanoic acid unit (Dmhha). The absolute configurations of the six
      residues were determined by Marfey's analysis, chiral HPLC analysis, and GC/MS
      analysis of the hydrolysate. Morphological and phylogenetic studies revealed the
      sample to be composed of a Lyngbya majuscula-Centroceras sp. association. MALDI
      imaging analysis of the cultured L. majuscula indicated that it was the true
      producer of this new depsipeptide. Pure palmyramide A showed sodium channel
      blocking activity in neuro-2a cells and cytotoxic activity in H-460 human lung
      carcinoma cells.

PMID- 19839607
TI  - Fullerene nanoparticles selectively enter oxidation-damaged cerebral microvessel
      endothelial cells and inhibit JNK-related apoptosis.
AB  - There is a dearth in fundamental cellular-level understanding of how
      nanoparticles interact with the cells of the blood brain barrier (BBB),
      particularly under the oxidative environment. The apoptosis of cerebral
      microvessel endothelial cells (CMECs) induced by oxidative stress injury plays a
      key role in the dysfunction of BBB. By use of CMECs as an in vitro BBB model, we
      show for the first time that C(60)(C(COOH)(2))(2) nanoparticles can selectively
      enter oxidized CMECs rather than normal cells, and maintain CMECs integrity by
      attenuating H(2)O(2)-induced F-actin depolymerization via the observation of
      several state-of-the art microscopic techniques. Additionally, we have found that
      C(60)(C(COOH)(2))(2) nanoparticles greatly inhibit the apoptosis of CMECs induced
      by H(2)O(2), which is related to their modulation of the JNK pathway.
      C(60)(C(COOH)(2))(2) nanoparticles can regulate several downstream signaling
      events related to the JNK pathway, including reduction of JNK phosphorylation,
      activation of activator protein 1 (AP-1) and caspase-3, and inhibition of polyADP
      ribose polymerase (PARP) cleavage and mitochondrial cytochrome c release. Our
      results indicate that C(60)(C(COOH)(2))(2) nanoparticles possess a novel ability
      of selectively entering oxidation-damaged cerebral endothelial cells rather than
      normal endothelial cells and then protecting them from apoptosis.

PMID- 19839608
TI  - Ag/AgBr/WO(3).H(2)O: visible-light photocatalyst for bacteria destruction.
AB  - A new composite photocatalyst Ag/AgBr/WO(3).H(2)O was synthesized by reacting
      Ag(8)W(4)O(16) with HBr and then reducing some Ag(+) ions in the surface region
      of AgBr particles to Ag nanoparticles via the light-induced chemical reduction.
      Ag nanoparticles are formed from AgBr by the light-induced chemical reduction
      reaction. The Ag/AgBr particles are on the surface of WO(3).H(2)O and have
      irregular shapes with sizes varying between 63 and 442 nm. WO(3).H(2)O appears as
      flakes about 31 nm thick and 157-474 nm wide. The as-grown Ag/AgBr/WO(3).H(2)O
      sample shows strong absorption in the visible region because of the plasmon
      resonance of Ag nanoparticles in Ag/AgBr/WO(3).H(2)O. The ability of this
      compound to destroy E. coli and oxidize methylic orange under visible light was
      compared with those of other reference photocatalysts. Ag/AgBr/WO(3).H(2)O is a
      highly efficient photocatalyst under visible light. The Ag/AgBr/WO(3).H(2)O
      samples recovered from repeated photooxidation experiments are almost identical
      to the as-prepared samples, proving the stability of Ag/AgBr/WO(3).H(2)O sample.

PMID- 19839609
TI  - Large protein complexes with extreme rotational correlation times investigated in
      solution by magic-angle-spinning NMR spectroscopy.
AB  - We show that large protein complexes can be investigated in solution using magic
      angle-spinning (MAS) NMR spectroscopy without the need for sample crystallization
      or precipitation. In order to efficiently average anisotropic interactions with
      MAS, the rotational diffusion of the molecule has to be suppressed. This can be
      readily achieved by lowering the sample temperature and by adding glycerol to the
      protein solution. The approach is demonstrated using the human small heat shock
      protein (sHSP) alphaB-Crystallin, which forms oligomeric assemblies of
      approximately 600 kDa. We suggest this scheme as an approach for overcoming size
      limitations imposed by overall tumbling in solution-state NMR investigations of
      large protein complexes.

PMID- 19839610
TI  - Sequence specific interaction between promoter DNA and Escherichia coli RNA
      polymerase: comparative thermodynamic analysis with one immobilized partner.
AB  - Sequence specific interaction between DNA and protein molecules has been a
      subject of active investigation for decades now. Here, we have chosen single
      promoter containing bacteriophage DeltaD(III) T7 DNA and Escherichia coli RNA
      polymerase and followed their recognition at the air-water interface by using the
      surface plasmon resonance (SPR) technique, where the movement of one of the
      reacting species is restricted by way of arraying them on an immobilized support.
      For the Langmuir monolayer studies, we used a RNA polymerase with a histidine tag
      attached to one of its subunits, thus making it an excellent substrate for Ni(II)
      ions, while the SPR studies were done using biotin-labeled DNA immobilized on a
      streptavidin-coated chip. Detailed analysis of the thermodynamic parameters as a
      function of concentration and temperature revealed that the interaction of RNA
      polymerase with T7 DNA is largely entropy driven (83 (+/-12) kcal mol(-1)) with a
      positive enthalpy of 13.6 (+/-3.6) kcal mol(-1). The free energy of reaction
      determined by SPR and Langmuir-Blodgett technique was -11 (+/-2) and -15.6 kcal
      mol(-1), respectively. The ability of these methods to retain the specificity of
      the recognition process was also established.

PMID- 19839611
TI  - Hydrated structure of Ag(I) ion from symmetry-dependent, K- and L-edge XAFS
      multiple scattering and molecular dynamics simulations.
AB  - Details of the first-shell water structure about Ag(+) are reported from a
      corefinement of the K- and L(2)-edge multiple scattering signal in the X-ray
      absorption fine structure (XAFS) spectra. Detailed fits of the Ag K-edge data
      that include the contributions from multiple scattering processes in the hydrated
      ion structure cannot distinguish between models containing tetrahedral symmetry
      versus those containing collinear O-Ag-O bonds. However, we show that the
      multiple scattering oscillations at the L(2)-edges have distinctly different
      phase and amplitude functions than at the K-edge. These phase and amplitude
      functions depend not only on the symmetry of the multiple scattering paths but
      also on the nature of the final state electronic wave function probed by the
      dipole-allowed transition. Hence the multiple scattering portions of K- and L(2)
      edge spectra provide independent measurements of the local symmetry--not a
      redundant measurement as is commonly believed. On the basis of the enhanced
      information content obtained by the simultaneous assessment of both the K- and
      L(2)-edges, we report that the hydrated Ag(+) structure contains five or six
      water molecules in the first shell with a significant number of nearly collinear
      and 90 degrees O-Ag-O bond angles. Finally, the K- and L(2)-edge spectra are used
      to benchmark the hydration structure that is generated from both DFT-based and
      classical molecular dynamics simulations. Simulated first-shell structures are
      compared to the experimental structures.

PMID- 19839612
TI  - New type of Li ion conductor with 3D interconnected nanopores via polymerization
      of a liquid organic electrolyte-filled lyotropic liquid-crystal assembly.
AB  - A new type of polymer electrolyte material for Li ion transport has been
      developed. This material is based on a polymerizable lyotropic (i.e.,
      amphiphilic) liquid crystal (1) that forms a type-II bicontinuous cubic (Q(II))
      phase with the common liquid electrolyte, propylene carbonate (PC), and its Li
      salt solutions. The resulting cross-linked, solid-liquid nanocomposite has an
      ordered, three-dimensional interconnected network of phase-separated liquid PC
      nanochannels and exhibits a room-temperature ion conductivity of 10(-4) to 10(-3)
      S cm(-1) when formed with 15 wt % 0.245 M LiClO(4)-PC solution. This value
      approaches that of conventional gelled poly(ethylene oxide)-based electrolytes
      blended with larger amounts of higher-concentration Li salt solutions. It is also
      similar to that of a bulk 0.245 M LiClO(4)-PC solution measured using the same AC
      impedance methods. Preliminary variable-temperature ion conductivity and NMR DOSY
      studies showed that liquidlike diffusion is present in the Q(II) nanochannels and
      that good ion conductivity ( approximately 10(-4) S cm(-1)) and PC mobility are
      retained down to -35 degrees C (and lower). This type of stable, liquidlike ion
      conductivity over a broad temperature range is typically not exhibited by
      conventional gelled-polymer- or liquid-crystal-based electrolytes, making this
      new material potentially valuable for enabling Li ion batteries that can operate
      more efficiently over a wider temperature range.

PMID- 19839613
TI  - Axial chirality control during Suzuki-Miyaura cross-coupling reactions: the tert
      butylsulfinyl group as an efficient chiral auxiliary.
AB  - An efficient route to a new family of axially chiral biaryl ligands by a Suzuki
      Miyaura cross-coupling reaction between ortho,ortho'-disubstituted aryl iodides
      bearing in ortho position a tert-butyl or p-tolylsulfinyl group and ortho
      substituted phenyl boronic acids or esters is described. The comparison between
      the t-BuSO and p-TolSO groups as chiral controllers is reported. The modularity
      of the approach is demonstrated by the preparation of a variety of enantiopure
      axially chiral mixed S/N and S/P ligands.

PMID- 19839615
TI  - A computational study of the effects of different solvents on the characteristics
      of the intramolecular hydrogen bond in acylphloroglucinols.
AB  - Acylphloroglucinols are a broad class of compounds, derivatives from 1,3,5
      trihydroxybenzene, and exhibiting a variety of biological activities. They are
      characterized by the presence of at least one COR group, whose sp(2) O can form
      an intramolecular hydrogen bond with a neighboring phenolic OH. This H-bond plays
      dominant roles in determining conformational preferences and energy, and is
      expected to play significant roles in biological activity mechanisms, which
      strongly motivates the study of its characteristics in solution. A computational
      study of a representative number of actual and model structures with different R
      was carried out in three solvents with different polarities and different types
      of interactions with solute molecules: water, acetonitrile, and chloroform,
      utilizing the PCM model. Calculations were mostly performed at the HF/6-31G(d,p)
      level because of affordability reasons in view of the size and number of the
      structures considered (the smallest structures were also calculated at MP2/6
      31+G(d,p) level). Comparison with the results of a previous study in vacuo shows
      similar patterns within each medium, pointing to similarities in the influence of
      relevant geometry factors on the characteristics of the H-bond. The medium
      appears to have little influence on the parameters of the H-bond. Comparison
      across media of the energy increase on H-bond removal (an indication of the H
      bond strength) is complicated by the greater solvent stabilization of the
      conformer resulting from H-bond removal, with respect to the one in which the H
      bond is present. Several factors, however, would point to a strength not too
      different from that observed in vacuo.

PMID- 19839614
TI  - Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana
      (mangosteen).
AB  - Bioassay-guided fractionation of a chloroform-soluble extract of Garcinia
      mangostana stem bark, using the HT-29 human colon cancer cell line and an enzyme
      based ELISA NF-kappaB assay, led to the isolation of a new xanthone, 11-hydroxy-3
      O-methyl-1-isomangostin (1). The structure of 1 was elucidated by spectroscopic
      data analysis. In addition, 10 other known compounds, 11-hydroxy-1-isomangostin
      (2), 11alpha-mangostanin (3), 3-isomangostin (4), alpha-mangostin (5), beta
      mangostin (6), garcinone D (7), 9-hydroxycalabaxanthone (8), 8-deoxygartanin (9),
      gartanin (10), and cratoxyxanthone (11), were isolated. Compounds 4-8 exhibited
      cytotoxicity against the HT-29 cell line with ED50 values of 4.9, 1.7, 1.7, 2.3,
      and 9.1 microM, respectively. In an ELISA NF-kappaB assay, compounds 5-7, 9, and
      10 inhibited p65 activation with IC50 values of 15.9, 12.1, 3.2, 11.3, and 19.0
      microM, respectively, and 6 showed p50 inhibitory activity with an IC50 value of
      7.5 microM. Alpha-mangostin (5) was further tested in an in vivo hollow fiber
      assay, using HT-29, LNCaP, and MCF-7 cells, but it was found to be inactive at
      the highest dose tested (20 mg/kg).

PMID- 19839616
TI  - Solution-liquid-solid growth of ternary Cu-In-Se semiconductor nanowires from
      multiple- and single-source precursors.
AB  - Ternary CuInSe(2) nanowires were synthesized for the first time by the solution
      liquid-solid (SLS) mechanism. Here, both metal-organic multiple- and single
      source molecular precursors were thermally decomposed in the presence of molten
      metal nanoparticles and coordinating ligands. The nature of the precursor
      multiple- compared to single-source (wherein Cu-Se-In bonds are effectively
      preformed)-as well as the choice of coordinating ligands, reaction temperature,
      and reactant order-of-addition strongly affected the morphology and composition
      of the reaction product obtained. Crystalline, straight, and nearly
      stoichiometric CuInSe(2) nanowires were most readily achieved using the single
      source precursor; however, careful tuning of reaction conditions could also be
      used to obtain high-quality nanowires from multiple-source precursor systems. The
      CuInSe(2) nanowires are strong light absorbers from the near-infrared through the
      visible and ultraviolet spectral regions and, thereby, comprise new soluble and
      processable "building blocks" for applications in solar-light harvesting.

PMID- 19839617
TI  - Investigation of the resonance Raman spectra and excitation profiles of a
      monometallic ruthenium(II) [Ru(bpy)2(HAT)]2+ complex by time-dependent density
      functional theory.
AB  - The resonance Raman (RR) properties of the [Ru(bpy)(2)(HAT)](2+) (where bpy =
      2,2'-bipyridine and HAT = 1,4,5,8,9,12-hexaazatriphenylene) complex have been
      investigated by means of time-dependent density functional theory calculations
      employing the hybrid B3LYP-35 XC functional and by including the effects of the
      solvent within the polarizable continuum model approach. Analysis of the
      electronic excited-state energies has demonstrated that mainly four different
      metal-to-ligand charge-transfer excitations contribute to the first absorption
      band in vacuo and water. The simulation of the absorption spectra by including
      the vibronic structure of the states has shown a general agreement with the
      experimental spectrum recorded in water. Furthermore, significant variations of
      the excited-state energies and compositions have been found when the effects of
      the solvent are included. Calculation of the short-time-approximation RR spectra
      has provided the vibrational signature of each contributing state and has shown
      that considering only one excited state is not sufficient to accurately simulate
      the RR spectra for excitation frequencies in resonance with the first absorption
      band. A comparison of the RR spectra calculated using the vibronic theory for
      different excitation wavelengths with the measured spectra at 514 and 458 nm has
      demonstrated that inclusion of the solvent effects in the simulation scheme leads
      to substantial improvements of the RR intensity patterns, which allow assignment
      of the vibrational bands. In particular, the calculations are able to reproduce
      the variations of the HAT and bpy RR intensities as illustrated by their RR
      excitation profiles, highlighting the strong dependence of the RR intensities
      with respect to the excitation frequency.

PMID- 19839618
TI  - A theoretical study of the decomposition mechanisms in substituted o
      nitrotoluenes.
AB  - The pathways corresponding to the most energetically favorable decomposition
      reactions that can be envisaged for o-nitrotoluene (and 20 of its derivatives)
      have been studied, using density functional theory, in order to evaluate the
      influence of substituents' nature (nitro, methyl, amino, carboxylic acid, and
      hydroxyl) and position. The first mechanism consists of the direct dissociation
      (homolysis) of the carbon nitrogen bond (CH(3)C(6)H(4)NO(2) = CH(3)C(6)H(4) +
      NO(2)) whereas the second one is a more complex process initiated by C-H alpha
      attack and leading to the formation of anthranil and water (C(6)H(4)C(H)ON +
      H(2)O). For each compound, the initial step of this last channel is the rate
      limiting one, the Gibbs activation energy of all systems being very close, that
      is all in the 40-44 kcal/mol range. More important variations have been observed
      for the C-NO(2) homolysis Gibbs activation energies (46-60 kcal/mol). These
      variations have been related to electron donor-acceptor properties of
      substituents by considering significant correlations (R(2) > 0.9) with the
      Hammett parameters (sigma). Nevertheless, though the influence of substituents on
      the direct breaking of the C-NO(2) bond was important, the C-H alpha attack
      remained finally the major decomposition channel for the studied compounds. Our
      study underlines the complexity of the decomposition process in nitroaromatic
      compounds and casts some doubts on the characterization of the energetic
      properties of such molecules only on the basis of C-NO(2) homolysis.

PMID- 19839619
TI  - Gold nanoparticles with externally controlled, reversible shifts of local surface
      plasmon resonance bands.
AB  - We have achieved reversible tunability of local surface plasmon resonance in
      conjugated polymer functionalized gold nanoparticles. This property was
      facilitated by the preparation of 3,4-ethylenedioxythiophene (EDOT) containing
      polynorbornene brushes on gold nanoparticles via surface-initiated ring-opening
      metathesis polymerization. Reversible tuning of the surface plasmon band was
      achieved by electrochemically switching the EDOT polymer between its reduced and
      oxidized states.

PMID- 19839620
TI  - Hydroperoxylation by hydroxyethylphosphonate dioxygenase.
AB  - Hydroxyethylphosphonate dioxygenase (HEPD) catalyzes the O(2)-dependent cleavage
      of the carbon-carbon bond of 2-hydroxyethylphosphonate (2-HEP) to afford
      hydroxymethylphosphonate (HMP) and formate without input of electrons or use of
      any organic cofactors. Two mechanisms have been proposed to account for this
      reaction. One involves initial hydroxylation of substrate to an acetal
      intermediate and its subsequent attack onto an Fe(IV)-oxo species. The second
      mechanism features initial hydroperoxylation of substrate followed by a Criegee
      rearrangement. To distinguish between the two mechanisms, substrate analogues
      were synthesized and presented to the enzyme. Hydroxymethylphosphonate was
      converted into phosphate and formate, and 1-hydroxyethylphosphonate was converted
      to acetylphosphate, which is an inhibitor of the enzyme. These results provide
      strong support for a Criegee rearrangement with a phosphorus-based migrating
      group and require that the O-O bond of molecular oxygen is not cleaved prior to
      substrate activation. (2R)-Hydroxypropylphosphonate partitioned between
      conversion to 2-oxopropylphosphonate and hydroxymethylphosphonate, with the
      latter in turn converted to phosphate and formate. Collectively, these results
      support a mechanism that proceeds by hydroperoxylation followed by a Criegee
      rearrangement.

PMID- 19839621
TI  - Synthetic control of green fluorescent protein.
AB  - Semisynthetic green fluorescent proteins (GFPs) can be prepared by producing
      truncated GFPs recombinantly and assembling them with synthetic beta-strands of
      GFP. The yield from expressing the truncated GFPs is low, and the chromophore is
      either partially formed or not formed. An alternative method is presented in
      which full-length proteins are produced recombinantly with a protease site
      inserted between the structural element to be removed and the rest of the
      protein. The native peptide can then be replaced by cutting the protease site
      with trypsin, denaturing in guanidine hydrochloride to disrupt the complex,
      separating the native peptide from the rest of the protein by size exclusion, and
      refolding the protein in the presence of a synthetic peptide. We show that this
      method allows for removal and replacement of the interior chromophore containing
      helix and that the GFP barrel is capable of inducing chromophore formation in a
      synthetic interior helix.

PMID- 19839623
TI  - Migration of photoinitiators by gas phase into dry foods.
AB  - Photoinitiators are components widely used in UV-cured inks for printing food
      packaging. In the present study, the migration of seven photoinitiators through
      the vapor phase was investigated. To perform the migration test, an additive
      enriched polyethylene wax was used as a source to release photoinitiators. The
      method was applied to evaluate the migration of the photoinitiators into five
      selected dry foods (cake, bread, cereals, rice and pasta). The highest level of
      migration was found in the cake. Parameters affecting the migration process were
      evaluated, and high migration level was found to correlate with both the porosity
      and the fat content. In addition, the kinetics of migration of the
      photoinitiators from the additive enriched wax into the cake were studied under
      accelerated conditions.

PMID- 19839625
TI  - Dissociative photoionization study of neopentane: a path to an accurate heat of
      formation of the t-butyl ion, t-butyl iodide, and t-butyl hydroperoxide.
AB  - The dissociation dynamics of energy selected neopentane, t-butyl iodide, and t
      butyl hydroperoxide ions have been investigated by threshold photoelectron
      photoion coincidence (TPEPICO) spectrometry. Although the methyl loss reaction
      from neopentane ions producing the t-butyl ion is in competition with a lower
      energy methane loss channel, modeling these two channels with the statistical
      theory of unimolecular decay provides a 0 K dissociation onset for methyl loss of
      10.564 +/- 0.025 eV. This leads to a 298 K t-butyl ion heat of formation of 714.3
      +/- 2.5 kJ x mol(-1), which is some 3 kJ x mol(-1) higher than the previously
      accepted value. The Delta(f)H degrees (298K)(t-C(4)H(9)(+)) combined with the
      measured 0 K onsets for t-C(4)H(9)(+) formation from t-butyl iodide (9.170 +/-
      0.007 eV) and from t-butyl hydroperoxide (9.904 +/- 0.012 eV), yields 298 K t
      butyl iodide and t-butyl hydroperoxide heats of formation of -68.5 +/- 2.6 kJ x
      mol(-1) and -233.2 +/- 2.8 kJ x mol(-1), respectively. Finally, the new t
      C(4)H(9)(+) heat of formation leads to a predicted adiabatic ionization energy
      for the t-butyl radical of 6.86 +/- 0.20 eV, and a 298 K proton affinity for
      isobutene of 798.8 +/- 2.5 kJ x mol(-1). The predicted ionization energy exceeds
      all measured values by 0.10 eV.

PMID- 19839622
TI  - Mitoxantrone analogues as ligands for a stem-loop structure of tau pre-mRNA.
AB  - A series of mitoxantrone (MTX) analogues have been designed, synthesized, and
      evaluated for binding to and stabilizing a stem-loop structure that serves as a
      splicing regulatory element in the pre-mRNA of tau, which is involved in
      Alzheimer's and other neurodegenerative diseases. Several compounds showed
      significantly improved binding activity relative to the original screening hit
      mitoxantrone. These findings establish essential structure-activity relationships
      to further optimize the activity of this promising class of compounds.

PMID- 19839626
TI  - Quantitatively interpreting thermal behavior of self-associating systems.
AB  - A general method is presented to extract thermodynamic as well as structural
      information from calorimetric data on self-associating systems using existing
      statistical thermodynamic models. The method is illustrated with one simple and
      one complex ligand binding system taken from the literature. The method is also
      used to extract the aggregation number using a simple mass balance model for self
      assembly of surfactant molecules, and experimental evidence is provided to
      support this.

PMID- 19839627
TI  - Excited-state dynamics of nitrated push-pull molecules: the importance of the
      relative energy of the singlet and triplet manifolds.
AB  - We present a study of the dynamics following photoexcitation in the first
      electronic band of NO(2)-para-substituted nitronaphthalenes. Our main goal was to
      determine the interplay between the nitro group, electron-donating substituents,
      and the solvent in defining the relative excited-state energies and their
      photoinduced pathways. We studied 4-nitro-1-naphthylamine and 1-methoxy-4
      nitronaphthalene in solution samples through femtosecond fluorescence up
      conversion and transient absorption techniques. In all solvents, both compounds
      have ultrafast fluorescence decays, showing that, similarly to the parent
      compound 1-nitronaphthalene, these molecules have highly efficient S(1) decay
      channels. The evolution of the transient absorption signals in the visible region
      reveals that for the methoxy-substituted compound, independently of solvent
      polarity, the photophysical pathways are the same as in 1-nitronaphthalene,
      namely, ultrafast intersystem crossing to an upper triplet state (receiver T(n)
      state) followed by relaxation into the lowest energy phosphorescent triplet T(1).
      In contrast, for the amino-substituted nitronaphthalene, the excited-state
      evolution shows a strong solvent dependence: In nonpolar solvents, the same type
      of intersystem crossing through an upper receiver triplet state dictates the
      photochemistry. However, in methanol, where the first singlet excited state shows
      an important solvent-induced stabilization, we observed typical signals of the
      repopulation of the electronic ground state in the time scale of less than 1 ps
      followed by vibrational cooling within S(0). Excited-state calculations at the
      time-dependent density functional level with the PBE0 functional give an
      approximate characterization of the states involved and appear to correlate well
      with the experimental results as they show that the S(1) state of the amino
      compound is stabilized with respect to upper triplet states only in the polar
      solvent. These findings sustain and illustrate the recent view that the
      intersystem crossing channel so prevalent in nitroaromatic compounds is related
      to an energy coincidence between the pi-pi* first singlet excited state and upper
      triplet states with n-pi* character. Our results indicate through direct
      observations that if the S(1) state is sufficiently stabilized, other rapid decay
      channels like internal conversion to the ground state will minimize the transfer
      of population to the triplet manifold.

PMID- 19839628
TI  - Solution structure of succinylacetone, an unsymmetrical beta-diketone, as studied
      by 13C NMR and GIAO-DFT calculations.
AB  - The enolization degrees of succinylacetone, an important heme biosynthesis
      inhibitor, have been determined in CDCl(3) and water solutions using (1)H NMR.
      The solution structures of SA have been investigated using a combined
      NMR/theoretical [GIAO DFT PBE1PBE/6-311++G(2d, p) PCM] approach. The populations
      of both enolic forms undergoing enol-enol equilibriums for SA and a series of
      unsymmetrical beta-diketones have been established by a quantitative comparison
      of the experimental (13)C NMR chemical shifts and calculated shielding constants.
      Moreover, using the same method and considering various trial structures
      differing in conformation and/or hydration of neutral SA molecule as well as its
      monoanion and dianion the structures of the most abundant species being present
      in the investigated water solutions have been deduced.

PMID- 19839629
TI  - Varying the electrochemical potential and thickness of porphyrazine SAMs by
      molecular design.
AB  - A series of multithiol-functionalized free-base and Zn-coordinated porphyrazines
      (pz's) have been prepared and characterized as self-assembled monolayers (SAMs)
      on Au. The synthetic flexibility of the pz's provides a unique opportunity to
      tune their electronic and chemical characteristics and to control the distance of
      the redox-active pz macrocycle from the Au surface. This allows us to study the
      reduction potentials of these surface-bound pz's as a function of film thickness
      and molecular charge distribution using angle-resolved X-ray photoelectron
      spectroscopy and cyclic voltammetry. Upon SAM formation, the reduction potentials
      of all pz's show a significant positive shift from their formal potentials when
      free in solution (up to approximately +1 V), with the magnitude of the shift
      inversely related to the Au-pz distance as determined from the film thickness of
      the pz SAM (thicknesses ranging from 3.5 to 11.8 A). When the pz lies down on the
      surface, in a SAM of thickness approximately 3.5 A, the charge distribution
      within a pz macrocycle also plays a role in determining the potential shift.
      These observations are consistent with our originally proposed mechanism for
      potential shifts upon binding to a metal surface based on image charge effects
      and with the analysis of Liu and Newton (J. Phys. Chem. 1994, 98, 7162).

PMID- 19839631
TI  - Structural analysis of PdAu dendrimer-encapsulated bimetallic nanoparticles.
AB  - PdAu dendrimer-encapsulated nanoparticles (DENs) were prepared via sequential
      reduction of the component metals. When Au is reduced onto 55-atom, preformed Pd
      DEN cores, analysis by UV-vis spectroscopy, electron microscopy, and extended X
      ray absorption fine structure (EXAFS) spectroscopy leads to a model consistent
      with inversion of the two metals. That is, Au migrates into the core and Pd
      resides on the surface. However, when Pd is reduced onto a 55-atom Au core, the
      expected Au core-Pd shell structure results. In this latter case, the EXAFS
      analysis suggests partial oxidation of the relatively thick Pd shell. When the
      DENs are extracted from their protective dendrimer stabilizers by alkylthiols,
      the resulting monolayer-protected clusters retain their original Au core-Pd shell
      structures. The structural analysis is consistent with a study of nanoparticle
      catalyzed conversion of resazurin to resorufin. The key conclusion from this work
      is that correlation of structure to catalytic function for very small, bimetallic
      nanoparticles requires detailed information about atomic configuration.

PMID- 19839632
TI  - Total synthesis of chloropeptin II (complestatin) and chloropeptin I.
AB  - The first total synthesis of chloropeptin II (1, complestatin) is disclosed. Key
      elements of the approach include the use of an intramolecular Larock indole
      synthesis for the initial macrocyclization, adopting conditions that permit
      utilization of a 2-bromoaniline, incorporating a terminal alkyne substituent (
      SiEt(3)) that sterically dictates the indole cyclization regioselectivity, and
      benefiting from an aniline protecting group (-Ac) that enhances the
      atropdiastereoselectivity and diminishes the strained indole reactivity toward
      subsequent electrophilic reagents. Not only did this key reaction provide the
      fully functionalized right-hand ring system of 1 in superb conversion (89%) and
      good atropdiastereoselectivity (4:1 R:S), but it also represents the first
      reported example of what will prove to be a useful Larock macrocyclization
      strategy. Subsequent introduction of the left-hand ring system enlisting an
      aromatic nucleophilic substitution reaction for macrocyclization with biaryl
      ether formation completed the assemblage of the core bicyclic structure of 1.
      Intrinsic in the design of the approach and by virtue of the single-step acid
      catalyzed conversion of chloropeptin II (1) to chloropeptin I (2), the route also
      provides a total synthesis of 2.

PMID- 19839633
TI  - Synthesis and evaluation of a stable bacteriochlorophyll-analog and its
      incorporation into high-density lipoprotein nanoparticles for tumor imaging.
AB  - The syntheses of novel near-infrared (NIR) dyes with excellent optical properties
      in biological tissues have driven the continued improvement of fluorescence
      imaging of deeply seated tumors. Bacteriochlorophyll a (Bchl), a dye synthesized
      by the phototrophic bacteria, R. sphaeroids, is particularly suited for deep
      tissue imaging due to its high absorbance coefficient and good fluorescence
      quantum yield in the NIR spectrum. However, obstacles that impede the development
      of this fluorophore are its poor stability and lack of tumor specificity. These
      issues ultimately limit its utility for tumor detection. Herein we describe a
      robust synthesis of a novel Bchl analog, bacteriochlorin e(6) bisoleate
      (BchlBOA), which is chemically stable, has excellent photophysical properties
      (ex, 752 nm; em, 762 nm) and is tailored for the incorporation into a tumor
      targetable high-density lipoprotein (HDL)-like nanoparticle (NP). Incorporating
      BchlBOA into HDL (HDL-BchlBOA) yielded 12 nm sized particles, corresponding well
      with the diameter of native HDL. Functional cell uptake studies showed that HDL
      BchlBOA was taken up by cells expressing the HDL receptor, scavenger receptor B
      type I (SR-BI), and was inhibited by 25-fold excess native HDL. Furthermore, the
      NP was successfully detected in KB cancer cells both in vitro and in tumor
      xenografts. Taken together, these results demonstrate that we successfully
      synthesized and formulated a stable analog of Bchl that is capable of being
      incorporated within HDL-like NPs for tumor-targeted imaging.

PMID- 19839634
TI  - Effects of sample preparation on bacterial colonization of polymers.
AB  - Characterization of materials developed for medical usage frequently includes
      studies in which the materials are inoculated with bacteria in order to assess
      bacterial colonization and biofilm formation. Observed differences in bacterial
      growth are typically considered to be due to the material or the incubation
      conditions. To our knowledge, the method used to prepare the materials has
      generally not been considered with regard to its influence on bacterial
      colonization. The objective of this study was to determine the effects that
      various preparation methods exert on bacterial colonization of polymer disks.
      Polymer disks of the same dimethacrylate composition were photopolymerized: (1)
      between untreated glass slides, (2) between polyester release film, (3) between
      glass slides treated with an alkyl silane, (4) between glass slides treated with
      a perfluorinated silane, or (5) with one free surface in an argon-purged chamber.
      Surface chemistry was quantified using X-ray photoelectron spectroscopy,
      hydrophobicity was assessed by water contact angle, and topography was
      characterized using atomic force microscopy. The disks were inoculated with
      Streptococcus mutans for 4 h, fixed, and visualized using confocal laser scanning
      microscopy. Differences among all groups were found with regard to surface
      chemistry, hydrophobicity, topography, and bacteria morphology, density, and
      coverage, indicating that the method of sample preparation strongly affects both
      the surface properties and the initial bacterial colonization. Polymerization on
      untreated slides was selected as the preferred method of preparation due to
      minimal material transfer to the polymer and consistent, reproducible bacterial
      colonization.

PMID- 19839635
TI  - Development of ELISAs for the class-specific determination of organophosphorus
      pesticides.
AB  - Enzyme-linked immunosorbent assays (ELISAs) for the class-specific determination
      of organophosphorus (OP) pesticides were developed from monoclonal antibodies
      raised against haptens with the functional group common to OP pesticides. To
      develop antigen-coated, indirect, competitive ELISAs, four haptens with different
      spacer arm structures were used to prepare antibodies, while eight haptens were
      tested for use as coating antigens. A total of 32 ELISAs were developed with one
      selected as the most suitable one based on average IC(50) and % CV values. The
      chosen ELISA showed class-selective response to O,O-diethyl phosphorothioate and
      phosphorodithioate OP pesticides with negligible cross-reactivity to other types
      of pesticides. Average IC(50) and % CV values of this ELISA for the 12 OP
      pesticides were 89 ng/mL and 96%, respectively. Compared to ELISAs previously
      developed with the same objective, the current ELISA demonstrates better
      sensitivity based on much lower mean IC(50) values in addition to improved class
      selective determination based on considerably lower % CV values as well as
      precise discrimination against other types of pesticides.

PMID- 19839636
TI  - The differences in surfactant adsorption on carbon nanotubes and their bundles.
AB  - Dissipative particle dynamics simulations of a mesoscale model are performed to
      investigate the concentration dependence of surfactant adsorption on small
      diameter carbon nanotubes and their bundles. Adsorption is found to follow
      fundamentally different mechanisms in the two cases because of the heterogeneity
      of the bundle surface and the difference in diameter of bundles compared to that
      of individual tubes. Whereas aggregation dominates adsorption on individual
      tubes, on bundles it is largely a Langmuir-type process. High adsorption energy
      sites on the outer surface of bundles, where surfactant molecules can interact
      with two tubes simultaneously, dominate at low coverage. They also cause
      adsorption on bundles to become significant well before adsorption on individual
      tubes starts. The difference in the adsorption mechanisms leads to a crossover
      point at higher concentrations, where the adsorbed amount per surface area on
      individual tubes becomes larger than that for the bundles.

PMID- 19839638
TI  - Salivary proteome changes as women age.

PMID- 19839637
TI  - Antiproliferation properties of grain sorghum dry distiller's grain lipids in
      Caco-2 cells.
AB  - Antiproliferative properties of lipids extracted from grain sorghum (GS) dry
      distiller's grain (DDG) were analyzed to determine the feasibility of developing
      GS coproducts as a source for human health dietary ingredients. The lipid extract
      of GS-DDG was delivered to human colon carcinoma (Caco-2) cells by solubilizing 0
      1000 microg/mL of GS-DDG lipids in 100 microg/mL increments with micelles. A
      significant reduction in cell viability (25-50%) resulted at treatment levels of
      400-1000 microg/mL GS-DDG lipids (p < 0.05). Alternatively, total protein levels
      of cells treated with 400, 500, and 600 microg/mL of GS-DDG lipid were not
      significantly different from the control, indicating cell growth during the
      treatment period. Total cell counts for the control were not significantly
      different from the GS-DDG lipid treated cells, but dead cell counts increased by
      approximately 10% for the latter sample with a concomitant increase of the
      intercellular protein lactate dehydrogenase leakage (30-40%) in the medium.
      Preliminary analysis by the fluorescence-activated cell method (FACs)
      demonstrated that nonviable cells were in either the early apoptotic, late
      apoptotic, or necrotic stage post-treatment with 400, 500, and 600 microg/mL GS
      DDG lipids. Physiochemical characterization of the GS-DDG lipids used for the
      antiproliferation study showed the presence of vitamin E (predominantly gamma
      tocopherol), triacylglycerides (predominantly linoleic acid), policosanols,
      aldehydes, and sterols (predominantly campesterol and stigmasterol), each of
      which or as synergistic/additive group of constituents may be responsible for the
      antiproliferative effect.

PMID- 19839639
TI  - Small discoidal pre-beta1 HDL particles are efficient acceptors of cell
      cholesterol via ABCA1 and ABCG1.
AB  - The aim of this study was to correlate the lipid content and size of discoidal
      reconstituted HDL particles with their ability to promote cellular cholesterol
      efflux. Homogeneous discoidal rHDL particles containing apoA-I and POPC, with
      diameters of 7.8, 9.6, 10.8, 12.5, and 17.0 nm, were prepared by the cholate
      dialysis technique. Cholesterol efflux to rHDL was evaluated in pathway-specific
      cell models for ABCA1-, ABCG1-, and SR-BI-mediated efflux. ABCA1-mediated efflux
      was efficiently promoted by the 7.8 nm rHDL containing 82 POPC molecules per
      particle. This rHDL also promoted ABCG1, but not SR-BI, cholesterol efflux. All
      large and lipid-rich rHDLs, with a diameter of >or=9.6 nm and a phospholipid
      content of >/=202 molecules per particle, promoted both SR-BI- and ABCG1-mediated
      efflux. Our results indicated that the ABCA1-mediated cell cholesterol efflux can
      be efficiently driven not only by monomolecular lipid free/poor apoA-I but also
      by a small discoidal phospholipid-containing particle resembling plasma pre-beta1
      HDL. This same particle also promotes ABCG1- but not SR-BI-mediated efflux. These
      results help to clarify the role of plasma pre-beta1 HDL in reverse cholesterol
      transport.

PMID- 19839640
TI  - Elastic, adhesive, and charge transport properties of a metal-molecule-metal
      junction: the role of molecular orientation, order, and coverage.
AB  - The elastic, adhesive, and charge transport properties of a metal-molecule-metal
      junction were studied via conducting-probe atomic force microscopy (AFM) and
      correlated with molecular structure by near-edge X-ray absorption fine structure
      (NEXAFS) spectroscopy. The junctions consisted of Co-Cr-coated AFM tips in
      contact with methyl-terminated alkanethiols (CH(3)(CH(2))(n-1)SH, denoted by
      C(n), where n is the number of carbons in the molecular chain) on Au substrates.
      AFM contact data were analyzed with the Derjaguin-Muller-Toporov contact model,
      modified by a first-order elastic perturbation method to account for substrate
      effects, and a parabolic tunneling model, appropriate for a metal-insulator-metal
      junction in which the thickness of the insulator is comparable to the Fermi
      wavelength of the conducting electrons. NEXAFS carbon K-edge spectra were used to
      compute the dichroic ratio R(I) for each film, which provided a quantitative
      measure of the molecular structure as a function of n. As n decreased from 18 to
      5, there was a change in the molecular phase from crystalline to amorphous (R(I) 
      -> 0) and loss of surface coverage, and as a result, the work of adhesion w
      increased from 82.8 mJ m(-2) to 168.3 mJ m(-2), the Young's modulus of the film
      E(film) decreased from 1.0 to 0.15 GPa, and the tunneling barrier height phi(0) -
      E(F) decreased from 2.4 to 2.1 eV. For all n, the barrier thickness t decreased
      for small applied loads F and remained constant at approximately 2.2 nm for large
      F. The change in behavior was explained by the presence of two insulating layers:
      an oxide layer on the Co-Cr tip, and the alkanethiol monolayer on the Au surface.
      X-ray photoelectron spectroscopy confirmed the presence of an oxide layer on the
      Co-Cr tip, and by performing high-resolution region scans through the film, the
      thickness of the oxide layer t(oxide) was found to be between 1.9 and 3.9 nm.
      Finally, it was shown that phi(0) - E(F) is strain-dependent, and the strain at
      which the film is completely displaced from under the tip is -0.17 for all values
      of n.

PMID- 19839641
TI  - Scientific and regulatory perspectives on metabolizing enzyme-transporter
      interplay and its role in drug interactions: challenges in predicting drug
      interactions.
AB  - Both metabolizing enzymes and drug transporters play important roles in
      modulating drug absorption, distribution, metabolism and elimination. Acting
      alone or in concert with each other they can affect the pharmacokinetics and
      pharmacodynamics of a drug. This paper will present cases from recent reviews of
      new drug application (NDA) and literature that exemplify the role of metabolizing
      enzyme-transporter interplay in a drug's disposition, and discuss challenges in
      predicting drug interactions. Finally, the discussion will focus on the need to
      leverage current knowledge to obtain more meaningful drug interaction
      information.

PMID- 19839642
TI  - The DEAD box helicase YxiN maintains a closed conformation during ATP hydrolysis.
AB  - DEAD box helicases unwind RNA duplexes at the expense of ATP hydrolysis.
      Recently, unwinding has been demonstrated in the absence of ATP hydrolysis.
      Herein, we show that ADP.BeF(x) supports RNA unwinding by YxiN, a DEAD box
      helicase that specifically recognizes a hairpin in 23S rRNA. ADP.AlF(x) and
      ADP.MgF(x) do not promote RNA unwinding, but all ATP analogues induce a closed
      conformation of the helicase core as required for RNA unwinding. Our results show
      that the interdomain cleft in the helicase core closes upon ATP binding at the
      beginning of the cycle. Reopening occurs after ATP hydrolysis, most likely
      coupled to phosphate release.

PMID- 19839643
TI  - Hepatitis C virus NS3 protease is activated by low concentrations of protease
      inhibitors.
AB  - The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) is a bifunctional
      enzyme with a protease and a helicase functionality located in each of the two
      domains of the single peptide chain. There is little experimental evidence for a
      functional role of this unexpected arrangement since artificial single domain
      forms of both enzymes are catalytically competent. We have observed that low
      concentrations of certain protease inhibitors activate the protease of full
      length NS3 from HCV genotype 1a with up to 100%, depending on the preincubation
      time and the inhibitor used. The activation was reduced, but not eliminated, by
      increased ionic strength, lowered glycerol concentration, or lowered pH. In all
      cases, it was at the expense of a significant loss of activity. Activation was
      not seen with the artificial protease domain of genotype 1b NS3 fused with a
      fragment of the NS4A cofactor. This truncated and covalently modified enzyme form
      was much less active and exhibited fundamentally different catalytic properties
      to the full-length NS3 protease without the fused cofactor. The most plausible
      explanation for the activation was found to involve a slow transition between two
      enzyme conformations, which differed in their catalytic ability and affinity for
      inhibitors. Equations derived based on this assumption resulted in better fits to
      the experimental data than the equation for simple competitive inhibition. The
      mechanism may involve an inhibitor-induced stabilization of the helicase domain
      in a conformation that enhances the protease activity, or an improved alignment
      of the catalytic triad in the protease. The proposed mnemonic mechanism and
      derived equations are viable for both these explanations and can serve as a basic
      framework for future studies of enzymes activated by inhibitors or other ligands.

PMID- 19839644
TI  - Denaturant-dependent conformational changes in a beta-trefoil protein: global and
      residue-specific aspects of an equilibrium denaturation process.
AB  - Conformational properties of the folded and unfolded ensembles of human
      interleukin-1 receptor antagonist (IL-1ra) are strongly denaturant-dependent as
      evidenced by high-resolution two-dimensional nuclear magnetic resonance (NMR),
      limited proteolysis, and small-angle X-ray scattering (SAXS). The folded ensemble
      was characterized in detail in the presence of different urea concentrations by
      (1)H-(15)N HSQC NMR. The beta-trefoil fold characteristic of native IL-1ra was
      preserved until the unfolding transition region beginning at 4 M urea. At the
      same time, a subset of native resonances disappeared gradually starting at low
      denaturant concentrations, indicating noncooperative changes in the folded state.
      Additional evidence of structural perturbations came from the chemical shift
      analysis, nonuniform and bell-shaped peak intensity profiles, and limited
      proteolysis. In particular, the following nearby regions of the tertiary
      structure became progressively destabilized with increasing urea concentrations:
      the beta-hairpin interface of trefoils 1 and 2 and the H2a-H2 helical region.
      These regions underwent small-scale perturbations within the native baseline
      region in the absence of populated molten globule-like states. Similar regions
      were affected by elevated temperatures known to induce irreversible aggregation
      of IL-1ra. Further evidence of structural transitions invoking near-native
      conformations came from an optical spectroscopy analysis of its single-tryptophan
      variant W17A. The increase in the radius of gyration was associated with a single
      equilibrium unfolding transition in the case of two different denaturants, urea
      and guanidine hydrochloride (GuHCl). However, the compactness of urea- and GuHCl
      unfolded molecules was comparable only at high denaturant concentrations and
      deviated under less denaturing conditions. Our results identified the role of
      conformational flexibility in IL-1ra aggregation and shed light on the nature of
      structural transitions within the folded ensembles of other beta-trefoil
      proteins, such as IL-1beta and hFGF-1.

PMID- 19839646
TI  - Dynamics and energetics of the base flipping conformation studied with base pair
      mimic nucleosides.
AB  - A base flipping conformation is found in many biological processes, including DNA
      repair and DNA and RNA modification processes. To investigate the dynamics and
      energetics of this unusual conformation in a double helix, base flipping induced
      by the base pair analogues of deoxyadenosine and deoxycytidine derivatives
      tethering a phenyl or naphthyl group was investigated. DNA strands bearing the
      base pair analogues stabilized the base flipping conformation of a complementary
      RNA, resulting in a site-specific hydrolysis by specific base catalysis.
      Measurements of the hydrolysis rate and the thermal stability of DNA/RNA duplexes
      suggested an unconstrained flexibility of the flipped-out ribonucleotide. As
      established in the base flipping by DNA repair and DNA and RNA modification
      enzymes, the results suggested that base flipping occurred in competition with
      base pair formation. In addition, the deoxycytidine derivatives discriminated G
      from I (inosine), with respect to the base pair interaction energy, as observed
      for a damaged base or a weakened base pair search by DNA repair proteins. The
      base pair mimic nucleosides would be useful for investigating the base flipping
      conformation under the equilibrium with base pairing.

PMID- 19839645
TI  - The human asparaginase-like protein 1 hASRGL1 is an Ntn hydrolase with beta
      aspartyl peptidase activity.
AB  - Herein we report the bacterial expression, purification, and enzymatic
      characterization of the human asparaginase-like protein 1 (hASRGL1). We present
      evidence that hASRGL1 exhibits beta-aspartyl peptidase activity consistent with
      enzymes designated as plant-type asparaginases, which had thus far been found in
      only plants and bacteria. Similar to nonmammalian plant-type asparaginases,
      hASRGL1 is shown to be an Ntn hydrolase for which Thr168 serves as the essential
      N-terminal nucleophile for intramolecular processing and catalysis, corroborated
      in part by abolishment of both activities through the Thr168Ala point mutation.
      In light of the activity profile reported here, ASRGL1s may act synergistically
      with protein l-isoaspartyl methyl transferase to relieve accumulation of
      potentially toxic isoaspartyl peptides in mammalian brain and other tissues.

PMID- 19839647
TI  - A hydrodynamic analysis of APOBEC3G reveals a monomer-dimer-tetramer self
      association that has implications for anti-HIV function.
AB  - The innate antiviral factor APOBEC3G (A3G) possesses RNA binding activity and
      deaminates HIV-1 DNA. High-molecular mass forms of A3G can be isolated from a
      variety of cell types but exhibit limited deaminase activity relative to low
      molecular mass species prepared under RNA-depleted conditions. To investigate the
      fundamental oligomeric state and shape of A3G, we conducted sedimentation
      velocity analyses of the pure enzyme under RNA-deficient conditions. The results
      reveal a predominant dimer in equilibrium with minor monomeric and tetrameric
      species. Hydrodynamic modeling of the dimer supports an extended cylindrical
      shape that assembles into an elongated tetramer. Overall, the results provide
      physical restraints for the A3G quaternary structure that have implications for
      modulating antiviral function.

PMID- 19839648
TI  - Kinetic characterization of xenobiotic reductase A from Pseudomonas putida 86.
AB  - Xenobiotic reductase A (XenA) from Pseudomonas putida is a member of the old
      yellow-enzyme family of flavin-containing enzymes and catalyzes the NADH/NADPH
      dependent reduction of various substrates, including 8-hydroxycoumarin and 2
      cyclohexenone. Here we present a kinetic and thermodynamic analysis of XenA. In
      the reductive half-reaction, complexes of oxidized XenA with NADH or NADPH form
      charge-transfer (CT) intermediates with increased absorption around 520-560 nm,
      which occurs with a second-order rate constant of 9.4 x 10(5) M(-1) s(-1) with
      NADH and 6.4 x 10(5) M(-1) s(-1) with NADPH, while its disappearance is
      controlled by a rate constant of 210-250 s(-1) with both substrates. Transfer of
      hydride from NADPH proceeds 24 times more rapidly than from NADH. This modest
      kinetic preference of XenA for NADPH is unlike the typical discrimination between
      NADH and NADPH by binding affinity. Docking studies combined with electrostatic
      energy calculations indicate that the 2'-phosphate group attached to the adenine
      moiety of NADPH is responsible for this difference. The reductions of 2
      cyclohexenone and coumarin in the oxidative half-reaction are both concentration
      dependent under the assay conditions and reveal a more than 50-fold larger
      limiting rate constant for the reduction of 2-cyclohexenone compared to that of
      coumarin. Our work corroborates the link between XenA and other members of the
      old-yellow-enzyme family but demonstrates several differences in the reactivity
      of these enzymes.

PMID- 19839650
TI  - The SH2 domains of inositol polyphosphate 5-phosphatases SHIP1 and SHIP2 have
      similar ligand specificity but different binding kinetics.
AB  - SH2 domain-containing inositol 5-phosphatases 1 (SHIP1) and 2 (SHIP2) are
      structurally similar proteins that catalyze the degradation of lipid secondary
      messenger phosphatidylinositol 3,4,5-triphosphate to produce phosphatidylinositol
      3,4-diphosphate. Despite their high sequence identity (51%), SHIP1 and SHIP2
      share little overlap in their in vivo functions. In this work, the sequence
      specificity of the SHIP2 SH2 domain was systematically defined through the
      screening of a combinatorial pY peptide library. Comparison of its specificity
      profile with that of the SHIP1 SH2 domain showed that the two SH2 domains have
      similar specificities, both recognizing pY peptides of the consensus sequence
      pY[S/Y][L/Y/M][L/M/I/V], although there are also subtle differences such as the
      tolerance of an arginine at the pY + 1 position by the SHIP2 but not SHIP1 SH2
      domain. Surface plasmon resonance analysis of their interaction with various pY
      peptides suggested that the two domains have similar binding affinities but
      dramatically different binding kinetics, with the SHIP1 SH2 domain having fast
      association and dissociation rates while the SHIP2 domain showing apparent slow
      binding behavior. Site-directed mutagenesis and kinetic studies indicated that
      the SHIP2 SH2 domain exists as a mixture of two conformational isomers. The
      major, inactive isomer apparently contains two cis peptidyl-prolyl bonds at
      positions 88 and 105, whereas the minor, active isomer has both proline residues
      in their trans configuration. Cis-trans isomerization of the peptidyl-prolyl
      bonds may provide a potential mechanism for regulating the interaction between
      SHIP2 and pY proteins. These data suggest that a combination of tissue
      distribution, specificity, and kinetic differences is likely responsible for
      their in vivo functional differences.

PMID- 19839649
TI  - Identification of specific transmembrane residues and ligand-induced interface
      changes involved in homo-dimer formation of a yeast G protein-coupled receptor.
AB  - The Saccharomyces cerevisiae alpha-factor pheromone receptor, Ste2p, has been
      studied as a model for G protein-coupled receptor (GPCR) structure and function.
      Dimerization has been demonstrated for many GPCRs, although the role(s) of
      dimerization in receptor function is disputed. Transmembrane domains one (TM1)
      and four (TM4) of Ste2p were shown previously to play a role in dimerization. In
      this study, single cysteine substitutions were introduced into a Cys-less Ste2p,
      and disulfide-mediated dimerization was assessed. Six residues in TM1 (L64 to
      M69) that had not been previously investigated and 19 residues in TM7 (T278 to
      A296) of which 15 were not previously investigated were mutated to create 25
      single Cys-containing Ste2p molecules. Ste2p mutants V68C in TM1 and nine mutants
      in TM7 (cysteine substituted into residues 278, 285, 289, and 291 to 296) showed
      increased dimerization upon addition of an oxidizing agent in comparison to the
      background dimers formed by the Cys-less receptor. The formation of dimers was
      decreased for TM7 mutant receptors in the presence of alpha-factor indicating
      that ligand binding resulted in a conformational change that influenced
      dimerization. The effect of ligand on dimer formation suggests that dimers are
      formed in the resting state and the activated state of the receptor by different
      TM interactions.

PMID- 19839651
TI  - Supramolecular interactions in chemomechanical polymers.
AB  - Molecular recognition is the basis for the operation of most biological
      functions; outside of nature, it has also been developed to a high degree of
      sophistication within the framework of supramolecular chemistry. More recently,
      selective noncovalent interactions, which constitute molecular recognition, are
      being used in intelligent new materials that transform chemical signals into
      actions, such as the release of drugs. The presence of supramolecular binding
      sites allows chemomechanical polymers to operate as sensors and actuators within
      a single unit without the need for any additional devices such as transducers or
      power supplies. A polymer can be designed so that a particular chemical
      substance, most often in aqueous surroundings, will trigger either a large
      expansion or a large contraction, depending on the mechanism. The translation of
      binding energy into mechanical motion can, with a suitable arrangement of the
      materials in tubes or on flexible films, be harnessed for unidirectional drives,
      flow control, the liberation of drugs, or the uptake of toxic compounds, among
      other applications. Miniaturization of the polymer particles allows one to
      enhance both the sensitivity and speed of the response, which is of particular
      importance in sensing. The basis for the selective response to external effector
      compounds, such as metal ions, amino acids, peptides, or nucleotides, is their
      noncovalent interaction with complementary functions covalently bound to the
      polymer network. With suitable polymers, selectivity between structural isomers,
      and even between enantiomers, as triggers can be achieved. As with supramolecular
      complexes in solution, the underlying interactions in polymers comprise a variety
      of noncovalent binding mechanisms, which are not easy to distinguish and
      quantify, and more so with polymers that are not monodisperse. In this Account,
      we present systematic comparisons of different polymers and effector classes that
      allow, for the first time, the characterization of these contributions in
      chemomechanical polymers: they comprise ion pairing, metal coordination,
      stacking, cation-pi, dispersive, and hydrophobic forces. In contrast, hydrogen
      bonding has a major role primarily in the hydrogel network structure itself. The
      fully reversible polymer volume changes are essentially determined by water
      uptake or release. In gels derived from boronic acid, glucose can serve as a
      cross-linking effector in promoting contractions via strong, reversible covalent
      bond formation in a highly distinctive manner. Cooperativity between two
      different effector compounds is more frequently seen with such polymers than in
      solution: it leads to logical AND gates by different motions of the particles,
      with a direct communication link to the outside world. For example, with a
      polymer that bears several recognition sites, triggering peptides induce motion
      only if Zn(2+) or Cu(2+) ions are simultaneously present. The molecular
      recognition mechanisms that cause volume changes in polymers share similarities
      with extensively studied supramolecular systems in solution, but there are also
      remarkable differences. In this Account, we bring the knowledge learned from
      solution studies to bear on our systematic analysis of polymeric systems in an
      effort to promote the effective harnessing of the forces involved in
      chemomechanical polymers and the smart materials that can be created with them.

PMID- 19839652
TI  - PIP(2)-binding site in Kir channels: definition by multiscale biomolecular
      simulations.
AB  - Phosphatidylinositol bisphosphate (PIP(2)) is an activator of mammalian inwardly
      rectifying potassium (Kir) channels. Multiscale simulations, via a sequential
      combination of coarse-grained and atomistic molecular dynamics, enabled
      exploration of the interactions of PIP(2) molecules within the inner leaflet of a
      lipid bilayer membrane with possible binding sites on Kir channels. Three Kir
      channel structures were investigated: X-ray structures of KirBac1.1 and of a
      Kir3.1-KirBac1.3 chimera and a homology model of Kir6.2. Coarse-grained
      simulations of the Kir channels in PIP(2)-containing lipid bilayers identified
      the PIP(2)-binding site on each channel. These models of the PIP(2)-channel
      complexes were refined by conversion to an atomistic representation followed by
      molecular dynamics simulation in a lipid bilayer. All three channels were
      revealed to contain a conserved binding site at the N-terminal end of the slide
      (M0) helix, at the interface between adjacent subunits of the channel. This
      binding site agrees with mutagenesis data and is in the proximity of the site
      occupied by a detergent molecule in the Kir chimera channel crystal. Polar
      contacts in the coarse-grained simulations corresponded to long-lived
      electrostatic and H-bonding interactions between the channel and PIP(2) in the
      atomistic simulations, enabling identification of key side chains.

PMID- 19839653
TI  - Multigenerational exposure of the estuarine sheepshead minnow (Cyprinodon
      variegatus) to 17 beta-estradiol. I. organism-level effects over three
      generations.
AB  - A 280-d study examined the effects of 17beta-estradiol (E2) on reproduction and
      development of the sheepshead minnow (Cyprinodon variegatus) exposed from the
      parental (F0) through three subsequent (F1, F2, and F3) generations and evaluated
      the need for multigenerational assessments of the risks of endocrine-disrupting
      chemicals. This first three-generation study exposed adult F0 and F1 fish to
      measured concentrations of 0.01, 0.04, 0.08, 0.2, and 0.3 MUg E2/L; the F2 and F3
      generations were exposed to 0.2 MUg E2/L or less. The cumulative 21-d production
      of normal embryos was significantly reduced in the F0 generation at 0.3 MUg E2/L
      and in the F1 and F2 generations at 0.08 MUg E2/L or more. The daily reproductive
      rate was significantly reduced in all three generations at 0.08 MUg E2/L or more
      during spawning days 8 to 14 and 15 to 21. The proportion of infertile eggs from
      F1 fish was significantly increased above that of the solvent controls at 0.04
      and 0.2 MUg E2/L and from F2 fish at 0.04 MUg E2/L or more. Changes in liver,
      kidney, and gonadal tissues were seen in the F0 and F1 generations exposed to 0.2
      MUg E2/L or more. The female gonadosomatic index was significantly decreased at
      0.3 MUg E2/L in the F0 and F1 generations. Estradiol affected the hepatosomatic
      index only in female F1 fish, but not in a dose-dependent manner. All F1 fish in
      0.3 MUg E2/L appeared to be phenotypically female. Our results indicate that life
      cycle exposure to E2 significantly decreased embryo production by F1 and F2 fish
      at concentrations lower than those affecting the F0 generation, and they
      emphasize the importance of evaluating the impact of an estrogenic chemical on
      reproduction through a minimum of two (F0 and F1) generations.

PMID- 19839654
TI  - Aqueous and dietary copper uptake and elimination in Daphnia magna determined by
      the 67cu radiotracer.
AB  - Among the many toxic metals, the biokinetics of copper (Cu) in the freshwater
      cladoceran Daphnia magna have not been studied due to the lack of an ideal
      radiotracer. In the present study, a gamma radiotracer, 67Cu (half-life = 61.9
      h), was used to study the uptake of copper from the dissolved and dietary phase
      and efflux in D. magna, an important toxicity testing species. The influx rate of
      Cu from the dissolved phase increased with dissolved Cu concentration, with a
      calculated uptake rate constant of 0.055 L/g/h. The assimilation efficiency (AE)
      of Cu decreased significantly (from 92 to 16%) as the available food
      concentration increased, and the AE differed among the food types. As low as 1%
      of Cu AE was found in daphnids fed high concentrations (1.54 mg/L) of the green
      algae Chlorella pyrenoidosa. The AE decreased linearly as the ingestion rate of
      the daphnids increased. The efflux rate constant was 0.20/d at high food
      concentrations. Excretion accounted for 82 to 94% of total Cu loss from the
      animals, although Cu also was transferred maternally from female adults to their
      offspring. Under conditions of high food concentrations, approximately 6.5% of
      the mother's Cu was transferred to the offspring over 7 d. It was concluded that
      Cu accumulation is dominated by uptake from dietary sources, and there is a
      substantial need to understand the dietary toxicity of Cu to daphnids. The
      present study has implications for the choice of food particles in conducting the
      Cu toxicity testing in cladocerans.

PMID- 19839656
TI  - Workload, control, and social support effects on serum lipids: a longitudinal
      study among apparently healthy employed adults.
AB  - The authors investigated the direct and interactive effects of the job demand-
      control-support (JDC-S) model's components on subsequent changes in high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides
      (TRI) separately for male and female employees. In contrast to all 14 past
      studies on these relationships, the authors used a longitudinal design. Study
      participants (N = 1,137, 66% men) were all apparently healthy employees who
      underwent a routine health check at 2 points in time (Time 1 and Time 2) about 22
      months apart. In these analyses, the authors controlled for the Time 1 level of
      each criterion and for other confounders. Most of the direct and moderating
      effects found did not support the predictions of the JDC-S model; this finding is
      in agreement with the majority of past cross-sectional studies. The authors did
      not find any evidence supporting the existence of a reverse causation for either
      of the components of the JDC-S model. The authors suggest that serum lipids may
      not be a physiological mechanism mediating the effects of the JDC-S model on
      atherosclerotic diseases.

PMID- 19839657
TI  - The association of distress and sleeping problems with physicians' intentions to
      change profession: the moderating effect of job control.
AB  - The present study examined whether job control moderated the association between
      stress indicators (distress and sleeping problems) and intentions to change
      profession among 2,650 Finnish physicians. Ordinal logistic regression analysis
      was applied. The authors found that high levels of distress and sleeping problems
      were associated with higher levels of intentions to change profession, whereas
      high job control was associated with lower levels of intentions to change
      profession even after adjusting for the effects of gender, age, and employment
      sector. In addition, high job control was able to mitigate the positive
      association that distress and sleeping problems had with intentions to change
      profession. Our findings highlight the importance of offering more job control to
      physicians to prevent unnecessary physician turnover.

PMID- 19839658
TI  - Bridge employment and retirees' health: a longitudinal investigation.
AB  - The present study examined the relationship between bridge employment and
      retirees' health outcomes (i.e., major diseases, functional limitations, and
      mental health). We used a nationally representative sample of 12,189 retirees
      from the first 4 waves of the Health and Retirement Study. Hierarchical
      regression analyses showed that compared with full retirement, engaging in bridge
      employment either in a career field or in a different field was associated with
      fewer major diseases and functional limitations, whereas engaging in career
      bridge employment was associated with better mental health. The findings
      highlight the health benefits of engaging in bridge employment for retirees. The
      practical implications of this study are discussed at both the individual and
      policy levels. Limitations of the current findings are also noted in conjunction
      with future research directions.

PMID- 19839659
TI  - Sexual harassment and health among male and female police officers.
AB  - The aims of this study were to investigate whether sexual harassment is related
      to mental and physical health of both men and women, and to explore the possible
      moderating effects of gender on the relation between sexual harassment and
      health. In addition, we investigated whether women were more often bothered by
      sexual harassment than men, and whether victims who report being bothered by the
      harassment experience more health problems compared to victims who did not feel
      bothered. A representative sample of 3,001 policemen and 1,295 policewomen in the
      Dutch police force filled out an Internet questionnaire. It appeared that women
      were more often bothered by sexual harassment than men, but gender did not
      moderate the relation between sexual harassment and mental and physical health.
      In addition, victims who felt bothered by the harassing behaviors reported more
      mental and physical health problems than victims who did not feel bothered. The
      distinction between bothered and nonbothered victims is important because
      appraisal is an essential aspect in the operationalization of sexual harassment.

PMID- 19839660
TI  - The economic impact of work and family issues: child care satisfaction and
      financial considerations of employed mothers.
AB  - This article introduces the role of financial considerations into work-family
      research by considering the costs and benefits of employed mothers' child care
      satisfaction. Data from 2 samples offer empirical support for the addition of a
      fourth factor to a current measure of child care satisfaction so that the measure
      reflects mothers' satisfaction not only with caregiver attentiveness,
      communication, and dependability but also with child care-related financial
      considerations. This article also discusses relationships between child care
      satisfaction and work-family conflict and job satisfaction for this population.
      The results of this study provide both organizations and child care providers
      with a broader picture of the concerns that employed mothers face as they search
      for reliable, affordable child care.

PMID- 19839661
TI  - Structure and correlates of spillover from nonwork to work: an examination of
      nonwork activities, well-being, and work outcomes.
AB  - Employees today are involved in many different types of activities outside of
      work, including family, volunteering, leisure, and so on. The purpose of this
      study was to understand how participation in such nonwork activities can both
      enrich and interfere with well-being and behavior at work. Four dimensions of
      nonwork-to-work spillover were examined to better understand this process (i.e.,
      positive emotional, negative emotional, positive behavioral, and negative
      behavioral). Survey data were collected in 2 waves from 293 staff and faculty
      members of a large Canadian university (N = 108 matched surveys from both waves).
      We found that volunteering is associated with increased well-being and work
      satisfaction, and that it creates positive emotional and behavioral, and negative
      behavioral spillovers. We also found that sports, recreation, and fitness are
      associated with improved well-being and positive emotional spillover. Negative
      spillover is associated with negative outcomes.

PMID- 19839662
TI  - Effects of work-family conflict on employees' well-being: the moderating role of
      recovery strategies.
AB  - Based on the effort-recovery model, this study links work-family conflict (WFC)
      and family-work conflict (FWC) with the concept of recovery. The authors
      hypothesize that 2 recovery strategies-psychological detachment from work and
      verbal expression of emotions-moderate the relationship of these 2 types of
      conflict with 2 indicators of well-being, namely psychological strain and life
      satisfaction. For our sample of 128 emergency professionals from Spain,
      psychological detachment from work moderated the relationship between WFC and
      psychological strain, and between FWC and life satisfaction. Verbal expression of
      emotions moderated the relationship between both types of conflict and
      psychological strain.

PMID- 19839663
TI  - Beyond work and family: a measure of work/nonwork interference and enhancement.
AB  - Though early research on the work/nonwork interface was broader in scope, most
      recent research has focused on the interface between work and family. There is a
      need for an inclusive, validated measure of work/nonwork interference and
      enhancement that is appropriate for all workers regardless of their marital or
      family life status. The authors report here on 3 studies in which they develop a
      theoretically grounded and empirically validated multidimensional, bidirectional
      measure of work/nonwork interference and enhancement. All scale items refer to
      work/nonwork, whereas previous measures have mixed work/family and work/nonwork
      items or emphasize family roles in the nonwork domain. Quantitative analysis of
      the scale items yielded 17 items to measure work interference with personal life,
      personal life interference with work, work enhancement of personal life, and
      personal life enhancement of work. Confirmatory factor analyses and structural
      equation modeling results provide evidence for convergent, discriminant, and
      criterion-related validity for the scale from 2 large samples of workers (N =
      540, N = 384) across multiple job types and organizations.

PMID- 19839665
TI  - Parenting and homelessness: overview and introduction to the Special Section.
AB  - This overview of parenting and homelessness includes the characteristics and
      needs of families who are homeless, with a focus on the unique challenges faced
      by mothers, fathers, and children. In addition, the authors discuss how homeless
      families are narrowly defined based on the family members who present at shelters
      and other service programs. In order to fully support parents and their children
      as they exit homelessness, homeless service programs should consider the broader
      context of the nontraditional family system and support networks. The overview
      also includes common challenges to parenting while homeless, a summary of the
      articles in the Special Section, and recommendations for research, practice, and
      policy.

PMID- 19839666
TI  - Commentary: a consumer perspective on parenting while homeless.

PMID- 19839667
TI  - Commentary: a provider perspective on supporting parents who are homeless.

PMID- 19839669
TI  - What research tells us about the intersecting streams of homelessness and foster
      care.
AB  - This paper reviews mounting evidence linking foster care and homelessness and
      considers new approaches for intervention. Although there is no causal evidence
      that family homelessness leads to foster care or vice versa, the association no
      longer originates solely from samples of homeless people, but also from samples
      of people with childhood histories of foster care. Many programs work with
      families, children or youth based on their current living situations and limits
      imposed by funders. This results in discontinued services when the living
      situations change. Given the strong and consistent associations between
      homelessness and foster care, a better approach is to design programs that work
      with transient families regardless of their living situation. Parenting is key.
      Whether the parents are living with their children in homeless circumstances or
      are formerly homeless parents working to reunify with their children,
      coordinated, comprehensive, trauma-informed and family focused programs are
      needed to support parenting and family stability.

PMID- 19839668
TI  - Parent-adolescent violence and later behavioral health problems among homeless
      and housed youth.
AB  - Parent-adolescent violence (i.e., violence between parents and adolescents) is an
      important pathway to homelessness and predicts poor behavioral health outcomes
      among youth. However, few studies have examined links between parent violence and
      outcomes among youth who are homeless. Existing research has also tended to
      ignore adolescent violence toward parents, despite evidence that mutual violence
      is common. The current study examines prospective links of parent-adolescent
      violence to outcomes among youth who were homeless and demographically matched
      youth, through two complementary substudies: (a) an exploratory factor analysis
      (EFA) of items measuring parent and adolescent violence combined in the same
      analysis; and (b) an examination of predictive relationships between the factors
      identified in the EFA and behavioral health problems, including mental health and
      alcohol abuse problems. Predictive relationships were examined in the overall
      sample and by gender, ethnic, and housing status subgroups. Results of the EFA
      suggested that parent-adolescent violence includes intraindividual (i.e.,
      separate parent and adolescent) physical components and a shared psychological
      component. Each of these components contributed uniquely to predicting later
      youth behavioral health. Implications for research and practice with youth who
      are homeless are discussed.

PMID- 19839670
TI  - Examining the impact of parental risk on family functioning among homeless and
      housed families.
AB  - The present study used data from 132 families that were homeless and a comparison
      group of 434 housed families in order to compare family functioning across the
      two groups. Family functioning was assessed by family support workers when the
      families sought help from one of seven family service agencies in Washington, DC.
      Multiple regression models showed that there were few differences between
      homeless and housed families; a difference that did emerge showed that homeless
      families fared better than housed families in terms of children's developmental
      stimulation. However, when considering the compounding effects of additional
      family risk factors, adverse effects of homelessness were observed. As compared
      with housed families, homeless families with a history of parental mental illness
      had limited access to support networks and poorer interactions with their
      children. Poor financial and living conditions were observed among homeless
      families with histories of substance use. Policy implications and directions for
      future research are discussed.

PMID- 19839671
TI  - Parenting, parental mental health, and child functioning in families residing in
      supportive housing.
AB  - Long-term homelessness is associated with other psychosocial risk factors (e.g.,
      adult mental illness, substance abuse, and exposure to violence). All of these
      factors are associated with impairments in parenting effectiveness and child
      adjustment, but there are very limited data investigating parenting among
      families who are homeless and highly mobile. In particular, there is no
      literature examining the relationships among observed parenting, parental mental
      health, and child adjustment in a supportive housing sample. Data are reported
      from a multimethod study of 200 children in 127 families residing in supportive
      housing agencies in a large metro area. Observed parenting and parents' mental
      health symptoms directly affected children's adjustment. The influence of
      parenting self-efficacy on children's adjustment was mediated through its impact
      on observed parenting. However, observed parenting did not mediate the
      relationship between parental mental health and child adjustment. Implications
      for research and practice with homeless populations are offered.

PMID- 19839672
TI  - Effects of social support and conflict on parenting among homeless mothers.
AB  - Research has shown that having a supportive social network is generally
      beneficial for individuals, particularly those who are homeless or at risk of
      homelessness. However, conflict within these networks may diminish the positive
      effects of social support on well-being, and these effects may be felt acutely
      within a vulnerable population with multiple needs. This study examined the
      impact of conflict and social support on parenting behaviors in a sample of
      mothers who are homeless and were involved in a study of case management
      interventions of varying intensity. We found that women who reported high
      emotional and instrumental social support self-reported greater improvements in
      parenting consistency over time than those who reported lower levels of support.
      However, three-way interactions showed that conflict in support networks was a
      risk factor for harsh parenting practices among participants who reported lower
      levels of instrumental social support. Results suggest that social support may
      enhance homeless mothers' ability to provide consistent parenting, but that these
      benefits may be undermined if conflict occurs in combination with limited levels
      of instrumental social support.

PMID- 19839673
TI  - Parenting adults who become homeless: variations in stress and social support.
AB  - This article focuses on the stressors of parenting an adult child who experiences
      homelessness. Parents whose adult children become homeless may provide support to
      this child, but they may also subsequently experience stress and require social
      support themselves. Findings from this study support the hypothesis that parents
      who spend more time or money helping their homeless adult offspring experience
      higher levels of stress. Results also show higher levels of stress among parents
      who helped with activities of daily living and among parents who worked to
      prevent harm involving their adult homeless offspring. Among 37 respondents, a
      majority of whom were African American mothers parenting homeless sons, parents
      who engaged in activities to prevent harm and parents who experienced stress from
      harm prevention received more extensive social support. Health and social service
      providers should recognize and respond to the financial, emotional, and temporal
      burdens of parenting an adult who becomes homeless. Service providers can both
      support people who become homeless and reinforce larger family systems,
      particularly in circumstances that involve more extensive parental support or
      more harmful situations.

PMID- 19839674
TI  - Conducting filial therapy with homeless parents.
AB  - Homelessness and the associated feelings of loss are highly distressing for
      parents and their children who experience them. The implications for young,
      homeless children are clinically significant, as these children tend to display
      higher rates of depressive, anxious feelings. The literature suggests that
      parents are especially challenged during a period of homelessness, as they cannot
      provide for their children financially or emotionally. Evidence-based mental
      health interventions, such as filial therapy, may assist the parent-child
      relationship by promoting healing during a highly distressing event such as
      homelessness. Filial therapy, derived from child-centered play therapy, teaches
      parents to play with their children to express feelings and gain mastery over
      difficult and often disturbing thoughts and emotions. This article's purpose is
      to (a) educate clinicians about the psychological complexities of homelessness
      with parents and their children and (b) highlight the benefits of using filial
      therapy as an evidence-based intervention with this population.

PMID- 19839675
TI  - Thriving as becoming resolute in narratives of women surviving childhood
      maltreatment.
AB  - The purpose of this feminist interpretive study was to portray the experience of
      women thriving after childhood maltreatment (CM) through personal narratives. An
      interdisciplinary team conducted multiple in-depth interviews of 44 women
      survivors of CM who identified themselves as successful and doing well. The
      interviews focused on "what worked" and "what did not" with the aim of exploring
      aftereffects of CM; strengths and strategies; interactions helpful in overcoming
      abuse; and related sociopolitical contexts. Narrative analyses revealed a
      distinct, dynamic process of becoming resolute characterized by six dimensions
      that were not sequential steps but characteristics, actions, and interactions.
      This study offers a new understanding of the experience of women gaining solid
      footing in their lives, the peace of knowing the abuse is over, and power to move
      in an upward trajectory.

PMID- 19839676
TI  - Sociocultural disadvantage, traumatic life events, and psychiatric symptoms in
      preadolescent children.
AB  - Previous research has demonstrated impact of psychosocial adversity on the mental
      health of children. This cross-sectional study examined specific influences of
      psychosocial adversity on internalizing versus externalizing symptoms, as
      explained by relative neighborhood disadvantage, sociocultural disadvantage, and
      exposure to interpersonal and non-interpersonal traumatic life events.
      Participants included 258 children aged 6 to 12 years from two Swedish elementary
      schools located in two socioeconomically distinct neighborhood settings.
      Information was obtained from their parents by means of questionnaires (a
      demographic form including information about parental occupation and country of
      origin, the Strengths and Difficulties Questionnaire and the Life Incidence of
      Traumatic Events checklist). Neighborhood differences in mental health were
      explained by variability in psychosocial adversity. While controlling for gender,
      age, and the other symptom dimension, sociocultural disadvantage was associated
      with internalizing but not with externalizing symptoms. In contrast, traumatic
      life events and especially interpersonal traumas were related to externalizing
      but not to internalizing symptoms. These findings provide some support for
      specificity of psychosocial adversities in the impact on child mental health.

PMID- 19839677
TI  - Traumatic events involving friends and family members in a sample of African
      American early adolescents.
AB  - The current study examines violent and nonviolent traumatic events involving
      friends and family members as predictors of PTSD, depression, internalizing, and
      externalizing behaviors in a sample of 403 African American early adolescents
      from chronically violent environments. Although there are many studies of urban
      children's exposure to community violence, few address the unique contribution of
      events involving significant others, and almost no research addresses African
      American youths' exposure to traumatic events other than violence. This study
      found that violent and nonviolent traumatic events were pervasive in the lives of
      these urban youth, and that they were as likely to report loss and injury of a
      close other through an accident as an act of violence. There were strong gender
      differences in the data. Unexpectedly, injury or loss of a close friend or family
      member from nonviolent events, but not from violent events, predicted PTSD,
      internalizing, and depression for boys. The results are discussed in terms of
      their implications for school-based universal interventions in communities where
      large numbers of children live with loss and trauma.

PMID- 19839678
TI  - Peer sexual harassment victimization at school: the roles of student
      characteristics, cultural affiliation, and school factors.
AB  - This study examines the links between students' reports of sexual harassment
      victimization by peers and a number of individual and school contextual factors.
      It is based on a nationally representative sample of 16,604 students in Grades 7
      through 11 in 327 schools across Israel who completed questionnaires during
      class. Hierarchical Linear Modeling was used to examine the links. Overall,
      approximately one in four students (25.6%) were victims of at least one unwanted
      and unwelcome act of harassment by peers (such as being touched or pinched in
      sexual manner) in the prior month. The most vulnerable groups were Israeli-Arab
      boys and students with negative perceptions of their school climate. The school
      correlates associated with higher levels of victimization were a higher share of
      students with less-educated parents, larger schools and classrooms, and negative
      school climate. The interactions between gender and school-related factors
      indicate that the gender patterns are different for Israeli-Arab and Jewish
      schools and for schools with different concentrations of students' families with
      low socioeconomic status. The study emphasizes the need for an ecological
      perspective in addressing school-based sexual harassment.

PMID- 19839679
TI  - Factors associated with the adjustment of foster children in the Netherlands.
AB  - Information obtained from 419 case files was used to investigate the associations
      between the foster child's adjustment to the foster family and factors in the
      histories of the child and the parents, as well as factors in the relationship
      between foster children and their biological parents while they are placed in
      foster care. Problems in the foster child's prior history, particularly
      attachment disorders and the experience of replacements, affect the extent of
      adjustment to the foster family. In-home visits by the child and the absence of
      parental permission to stay with the foster family are two factors related to the
      parent-child relationship that impeded adjustment. In general, parental problem
      factors did not affect adjustment. The fact that many foster children come from
      problem-laden backgrounds raises the question of whether foster parents are
      always sufficiently equipped to cope with these problems.

PMID- 19839680
TI  - Another breed of "service" animals: STARS study findings about pet ownership and
      recovery from serious mental illness.
AB  - This study elucidates the role of pets in recovery processes among adults with
      serious mental illness. Data derive from interviews with 177 HMO members with
      serious mental illness (52.2% women, average age 48.8 years) in the Study of
      Transitions and Recovery Strategies (STARS). Interviews and questionnaires
      addressed factors affecting recovery processes and included questions about pet
      ownership. Data were analyzed using a modified grounded theory method to identify
      the roles pets play in the recovery process. Primary themes indicate pets assist
      individuals in recovery from serious mental illness by (a) providing empathy and
      "therapy"; (b) providing connections that can assist in redeveloping social
      avenues; (c) serving as "family" in the absence of or in addition to human family
      members; and (d) supporting self-efficacy and strengthening a sense of
      empowerment. Pets appear to provide more benefits than merely companionship.
      Participants' reports of pet-related contributions to their well-being provide
      impetus to conduct more formal research on the mechanisms by which pets
      contribute to recovery and to develop pet-based interventions.

PMID- 19839681
TI  - Theory-based causal induction.
AB  - Inducing causal relationships from observations is a classic problem in
      scientific inference, statistics, and machine learning. It is also a central part
      of human learning, and a task that people perform remarkably well given its
      notorious difficulties. People can learn causal structure in various settings,
      from diverse forms of data: observations of the co-occurrence frequencies between
      causes and effects, interactions between physical objects, or patterns of spatial
      or temporal coincidence. These different modes of learning are typically thought
      of as distinct psychological processes and are rarely studied together, but at
      heart they present the same inductive challenge-identifying the unobservable
      mechanisms that generate observable relations between variables, objects, or
      events, given only sparse and limited data. We present a computational-level
      analysis of this inductive problem and a framework for its solution, which allows
      us to model all these forms of causal learning in a common language. In this
      framework, causal induction is the product of domain-general statistical
      inference guided by domain-specific prior knowledge, in the form of an abstract
      causal theory. We identify 3 key aspects of abstract prior knowledge-the ontology
      of entities, properties, and relations that organizes a domain; the plausibility
      of specific causal relationships; and the functional form of those relationships
      and show how they provide the constraints that people need to induce useful
      causal models from sparse data.

PMID- 19839682
TI  - Rational adaptation under task and processing constraints: implications for
      testing theories of cognition and action.
AB  - The authors assume that individuals adapt rationally to a utility function given
      constraints imposed by their cognitive architecture and the local task
      environment. This assumption underlies a new approach to modeling and
      understanding cognition-cognitively bounded rational analysis-that sharpens the
      predictive acuity of general, integrated theories of cognition and action. Such
      theories provide the necessary computational means to explain the flexible nature
      of human behavior but in doing so introduce extreme degrees of freedom in
      accounting for data. The new approach narrows the space of predicted behaviors
      through analysis of the payoff achieved by alternative strategies, rather than
      through fitting strategies and theoretical parameters to data. It extends and
      complements established approaches, including computational cognitive
      architectures, rational analysis, optimal motor control, bounded rationality, and
      signal detection theory. The authors illustrate the approach with a reanalysis of
      an existing account of psychological refractory period (PRP) dual-task
      performance and the development and analysis of a new theory of ordered dual-task
      responses. These analyses yield several novel results, including a new
      understanding of the role of strategic variation in existing accounts of PRP and
      the first predictive, quantitative account showing how the details of ordered
      dual-task phenomena emerge from the rational control of a cognitive system
      subject to the combined constraints of internal variance, motor interference, and
      a response selection bottleneck.

PMID- 19839684
TI  - Trichotomous processes in early memory development, aging, and neurocognitive
      impairment: a unified theory.
AB  - One of the most extensively investigated topics in the adult memory literature,
      dual memory processes, has had virtually no impact on the study of early memory
      development. The authors remove the key obstacles to such research by formulating
      a trichotomous theory of recall that combines the traditional dual processes of
      recollection and familiarity with a reconstruction process. The theory is then
      embedded in a hidden Markov model that measures all 3 processes with low-burden
      tasks that are appropriate for even young children. These techniques are applied
      to a large corpus of developmental studies of recall, yielding stable findings
      about the emergence of dual memory processes between childhood and young
      adulthood and generating tests of many theoretical predictions. The techniques
      are extended to the study of healthy aging and to the memory sequelae of common
      forms of neurocognitive impairment, resulting in a theoretical framework that is
      unified over 4 major domains of memory research: early development, mainstream
      adult research, aging, and neurocognitive impairment. The techniques are also
      extended to recognition, creating a unified dual process framework for recall and
      recognition.

PMID- 19839683
TI  - The influence of categories on perception: explaining the perceptual magnet
      effect as optimal statistical inference.
AB  - A variety of studies have demonstrated that organizing stimuli into categories
      can affect the way the stimuli are perceived. We explore the influence of
      categories on perception through one such phenomenon, the perceptual magnet
      effect, in which discriminability between vowels is reduced near prototypical
      vowel sounds. We present a Bayesian model to explain why this reduced
      discriminability might occur: It arises as a consequence of optimally solving the
      statistical problem of perception in noise. In the optimal solution to this
      problem, listeners' perception is biased toward phonetic category means because
      they use knowledge of these categories to guide their inferences about speakers'
      target productions. Simulations show that model predictions closely correspond to
      previously published human data, and novel experimental results provide evidence
      for the predicted link between perceptual warping and noise. The model unifies
      several previous accounts of the perceptual magnet effect and provides a
      framework for exploring categorical effects in other domains.

PMID- 19839685
TI  - Decision-tree models of categorization response times, choice proportions, and
      typicality judgments.
AB  - The authors present 3 decision-tree models of categorization adapted from T.
      Trabasso, H. Rollins, and E. Shaughnessy (1971) and use them to provide a
      quantitative account of categorization response times, choice proportions, and
      typicality judgments at the individual-participant level. In Experiment 1, the
      decision-tree models were fit to reaction time and choice proportion data from a
      study reported by A. L. Cohen and R. M. Nosofsky (2003). In Experiment 2,
      participants were also asked to provide typicality ratings for each stimulus. A
      process-tracing method called the "4-questions game" (Y. Sayeki, 1969) was used
      in a posttest phase to identify a decision tree for each participant. In both
      experiments, the decision-tree models explained a very high proportion of
      variance in the data and compared favorably with 2 leading exemplar models.

PMID- 19839686
TI  - Probability theory, not the very guide of life.
AB  - Probability theory has long been taken as the self-evident norm against which to
      evaluate inductive reasoning, and classical demonstrations of violations of this
      norm include the conjunction error and base-rate neglect. Many of these phenomena
      require multiplicative probability integration, whereas people seem more inclined
      to linear additive integration, in part, at least, because of well-known capacity
      constraints on controlled thought. In this article, the authors show with
      computer simulations that when based on approximate knowledge of probabilities,
      as is routinely the case in natural environments, linear additive integration can
      yield as accurate estimates, and as good average decision returns, as estimates
      based on probability theory. It is proposed that in natural environments people
      have little opportunity or incentive to induce the normative rules of probability
      theory and, given their cognitive constraints, linear additive integration may
      often offer superior bounded rationality.

PMID- 19839688
TI  - Bayes and the simplicity principle in perception.
AB  - Discussions of the foundations of perceptual inference have often centered on 2
      governing principles, the likelihood principle and the simplicity principle.
      Historically, these principles have usually been seen as opposed, but
      contemporary statistical (e.g., Bayesian) theory tends to see them as consistent,
      because for a variety of reasons simpler models (i.e., those with fewer
      dimensions or free parameters) make better predictors than more complex ones. In
      perception, many interpretation spaces are naturally hierarchical, meaning that
      they consist of a set of mutually embedded model classes of various levels of
      complexity, including simpler (lower dimensional) classes that are special cases
      of more complex ones. This article shows how such spaces can be regarded as
      algebraic structures, for example, as partial orders or lattices, with
      interpretations ordered in terms of dimensionality. The natural inference rule in
      such a space is a kind of simplicity rule: Among all interpretations
      qualitatively consistent with the image, draw the one that is lowest in the
      partial order, called the maximum-depth interpretation. This interpretation also
      maximizes the Bayesian posterior under certain simplifying assumptions,
      consistent with a unification of simplicity and likelihood principles. Moreover,
      the algebraic approach brings out the compositional structure inherent in such
      spaces, showing how perceptual interpretations are composed from a lexicon of
      primitive perceptual descriptors.

PMID- 19839689
TI  - A theory of utility conditionals: Paralogical reasoning from decision-theoretic
      leakage.
AB  - Many "if p, then q" conditionals have decision-theoretic features, such as
      antecedents or consequents that relate to the utility functions of various
      agents. These decision-theoretic features leak into reasoning processes,
      resulting in various paralogical conclusions. The theory of utility conditionals
      offers a unified account of the various forms that this phenomenon can take. The
      theory is built on 2 main components: (1) a representational tool (the utility
      grid), which summarizes in compact form the decision-theoretic features of a
      conditional, and (2) a set of folk axioms of decision, which reflect reasoners'
      beliefs about the way most agents make their decisions. Applying the folk axioms
      to the utility grid of a conditional allows for the systematic prediction of the
      paralogical conclusions invited by the utility grid's decision-theoretic
      features. The theory of utility conditionals significantly extends the scope of
      current theories of conditional inference and moves reasoning research toward a
      greater integration with decision-making research.

PMID- 19839690
TI  - The architecture of interdependent minds: A Motivation-management theory of
      mutual responsiveness.
AB  - A model of mutual responsiveness in adult romantic relationships is proposed.
      Behaving responsively in conflict-of-interest situations requires one partner to
      resist the temptation to be selfish and the other partner to resist the
      temptation to protect against exploitation. Managing risk and the attendant
      temptations of self-interest require the interpersonal mind to function in ways
      that coordinate trust and commitment across partners. The authors describe a
      system of procedural or "if... then" rules that foster mutuality in
      responsiveness by informing and motivating trust and commitment. The authors
      further argue that tuning rule accessibility and enactment to match the
      situations encountered in a specific relationship shapes its personality. By
      imposing a procedural structure on the interdependent mind, the proposed model of
      mutual responsiveness reframes interdependence theory and generates important
      research questions for the future.

PMID- 19839691
TI  - How cultural evolutionary theory can inform social psychology and vice versa.
AB  - Cultural evolutionary theory is an interdisciplinary field in which human culture
      is viewed as a Darwinian process of variation, competition, and inheritance, and
      the tools, methods, and theories developed by evolutionary biologists to study
      genetic evolution are adapted to study cultural change. It is argued here that an
      integration of the theories and findings of mainstream social psychology and of
      cultural evolutionary theory can be mutually beneficial. Social psychology
      provides cultural evolution with a set of empirically verified microevolutionary
      cultural processes, such as conformity, model-based biases, and content biases,
      that are responsible for specific patterns of cultural change. Cultural
      evolutionary theory provides social psychology with ultimate explanations for,
      and an understanding of the population-level consequences of, many social
      psychological phenomena, such as social learning, conformity, social comparison,
      and intergroup processes, as well as linking social psychology with other social
      science disciplines such as cultural anthropology, archaeology, and sociology.

PMID- 19839692
TI  - Do humans have two systems to track beliefs and belief-like states?
AB  - The lack of consensus on how to characterize humans' capacity for belief
      reasoning has been brought into sharp focus by recent research. Children fail
      critical tests of belief reasoning before 3 to 4 years of age (H. Wellman, D.
      Cross, & J. Watson, 2001; H. Wimmer & J. Perner, 1983), yet infants apparently
      pass false-belief tasks at 13 or 15 months (K. H. Onishi & R. Baillargeon, 2005;
      L. Surian, S. Caldi, & D. Sperber, 2007). Nonhuman animals also fail critical
      tests of belief reasoning but can show very complex social behavior (e.g., J.
      Call & M. Tomasello, 2005). Fluent social interaction in adult humans implies
      efficient processing of beliefs, yet direct tests suggest that belief reasoning
      is cognitively demanding, even for adults (e.g., I. A. Apperly, D. Samson, & G.
      W. Humphreys, 2009). The authors interpret these findings by drawing an analogy
      with the domain of number cognition, where similarly contrasting results have
      been observed. They propose that the success of infants and nonhuman animals on
      some belief reasoning tasks may be best explained by a cognitively efficient but
      inflexible capacity for tracking belief-like states. In humans, this capacity
      persists in parallel with a later-developing, more flexible but more cognitively
      demanding theory-of-mind abilities.

PMID- 19839693
TI  - Pseudodiagnosticity revisited.
AB  - In the psychology of reasoning and judgment, the pseudodiagnosticity task has
      been a major tool for the empirical investigation of people's ability to search
      for diagnostic information. A novel normative analysis of this experimental
      paradigm is presented, by which the participants' prevailing responses turn out
      not to support the generally accepted existence of a reasoning bias. The
      conclusions drawn do not rest on pragmatic concerns suggesting alleged
      divergences between the experimenter's and participants' reading of the task.
      They only rely, instead, on the demonstration that observed behavior largely
      conforms to optimal utility maximizing information search strategies for standard
      variants of the pseudodiagnosticity paradigm that have been investigated so far.
      It is argued that the experimental results obtained, contrary to what has
      recurrently been claimed, have failed to discriminate between normative and
      nonnormative accounts of behavior. More general implications of the analysis
      presented for past and future research on human information search behavior and
      diagnostic reasoning are discussed.

PMID- 19839694
TI  - A fundamental limitation of the conjunctive codes learned in PDP models of
      cognition: comment on Botvinick and Plaut (2006).
AB  - A central claim shared by most recent models of short-term memory (STM) is that
      item knowledge is coded independently from order in long-term memory (LTM; e.g.,
      the letter A is coded by the same representational unit whether it occurs at the
      start or end of a sequence). Serial order is computed by dynamically binding
      these item codes to a separate representation of order. By contrast, Botvinick
      and Plaut developed a parallel distributed processing (PDP) model of STM that
      codes for item-order information conjunctively, such that the same letter in
      different positions is coded differently in LTM. Their model supports a wide
      range of memory phenomena, and critically, STM is better for lists that include
      high, as opposed to low, sequential dependencies (e.g., bigram effects). Models
      with context-independent item representations do not currently account for
      sequential effects. However, we show that their PDP model is too sensitive to
      these effects. A modified version of the model does better but still fails in
      important respects. The successes and failures can be attributed to a fundamental
      constraint associated with context-dependent representations. We question the
      viability of conjunctive coding schemes to support STM and take these findings as
      problematic for the PDP approach to cognition more generally.

PMID- 19839695
TI  - Postscript: more problems with Botvinick and Plaut's (2006) PDP model of short
      term memory.

PMID- 19839696
TI  - Empirical and computational support for context-dependent representations of
      serial order: reply to Bowers, Damian, and Davis (2009).
AB  - J. S. Bowers, M. F. Damian, and C. J. Davis critiqued the computational model of
      serial order memory put forth in M. Botvinick and D. C. Plaut, purporting to show
      that the model does not generalize in a way that people do. They attributed this
      supposed failure to the model's dependence on context-dependent representations,
      translating this argument into a general critique of all parallel distributed
      processing models. The authors reply here, addressing both Bowers et al.'s
      criticisms of the Botvinick and Plaut model and the former's assessment of
      parallel distributed processing models in general.

PMID- 19839697
TI  - Postscript: winnowing out some take-home points.

PMID- 19839699
TI  - The dynamics of conditioning and extinction.
AB  - Pigeons responded to intermittently reinforced classical conditioning trials with
      erratic bouts of responding to the conditioned stimulus. Responding depended on
      whether the prior trial contained a peck, food, or both. A linear persistence
      learning model moved pigeons into and out of a response state, and a Weibull
      distribution for number of within-trial responses governed in-state pecking.
      Variations of trial and intertrial durations caused correlated changes in rate
      and probability of responding and in model parameters. A novel prediction--in the
      protracted absence of food, response rates can plateau above zero--was validated.
      The model predicted smooth acquisition functions when instantiated with the
      probability of food but a more accurate jagged learning curve when instantiated
      with trial-to-trial records of reinforcement. The Skinnerian parameter was
      dominant only when food could be accelerated or delayed by pecking. These
      experiments provide a framework for trial-by-trial accounts of conditioning and
      extinction that increases the information available from the data, permitting
      such accounts to comment more definitively on complex contemporary models of
      momentum and conditioning.

PMID- 19839700
TI  - Failure of retrospective revaluation to influence blocking.
AB  - In the blocking paradigm, subjects receive reinforced presentations of a
      compound, AX, after reinforced presentations of A alone. Following this training,
      responding to X is often diminished relative to a control group, which did not
      receive the prior training with A. Standard associative theories of learning such
      as the Rescorla-Wagner model (Rescorla & Wagner, 1972) explain this effect by
      assuming that A and X compete for control over behavior. In contrast, theories
      such as the comparator hypothesis assume that learning about X is unaffected by
      the properties of A, but it is the expression of this learning at test that is
      affected by the blocking manipulation. The aim of the 3 reported experiments was
      to distinguish between these 2 accounts. According to the comparator hypothesis,
      devaluing A following blocking should increase subsequent responding to X. In all
      3 experiments the blocking effect was found to persist following devaluation of
      A, providing support for standard associative theories.

PMID- 19839701
TI  - Enhancement of responding to A after A+/AX+ training: challenges for a comparator
      theory of learning.
AB  - Two appetitive Pavlovian conditioning experiments with rats investigated the
      associative changes that A undergoes in an A+/AX+ blocking procedure. Conditioned
      responding to A was enhanced relative to stimulus B, which had been conditioned
      in isolation (B+). This result was interpreted in terms of the formation of a
      within-compound association between A and X. The results of Experiment 2
      supported this conclusion by demonstrating that X had associative strength of its
      own and, furthermore, that extinguishing X resulted in a similar level of
      responding to A and B. These results are considered in terms of retrospective
      revaluation theories of learning.

PMID- 19839703
TI  - Contextual modulation of stimulus generalization in rats.
AB  - One connectionist analysis of the acquired equivalence/distinctiveness of cues
      assumes that when similar compounds (e.g., AX and BX) are paired with the same
      outcome (e.g., food, +; or no food, -), their components come to activate the
      same configural unit (ABX). When these compounds are paired with different
      outcomes, their components will come to address different units. Here, rats
      received appetitive training with eight compounds (e.g., AX+, BX+, CX-, DX-, AY+,
      BY-, CY-, DY+) that should generate the following configural units: ABX, CDX,
      ADY, and BCY. In Experiment 1, rats then received aversive conditioning to A,
      which should activate and revalue representations ABX and ADY. Subsequently,
      compounds that provided dual activation (i.e., BX and DY) of one of the revalued
      configural units (ABX and ADY) were shown to elicit greater fear than those
      compounds that provided a single source of activation to each unit (i.e., DX and
      BY). Experiment 2 confirmed and extended these findings. These results provide
      support for the connectionist analysis outlined above and are consistent with the
      application of this approach to the acquired equivalence/distinctiveness of cues.

PMID- 19839702
TI  - Protection from latent inhibition provided by a conditioned inhibitor.
AB  - Two conditioned suppression experiments with rats investigated the influence on
      latent inhibition of compounding a Pavlovian conditioned inhibitor with the
      target cue during preexposure treatment. Results were compared with those of
      subjects that received conventional latent inhibition training, no preexposure,
      or preexposure to the target cue in compound with a neutral stimulus. In
      Experiment 1, greater attenuation of the latent inhibition effect was observed in
      subjects that received target preexposure in compound with a Pavlovian
      conditioned inhibitor relative to subjects that received preexposure with a
      neutral stimulus or to the target alone. In Experiment 2, this protection from
      latent inhibition was attenuated if the excitor that was used to train the
      conditioned inhibitor was extinguished between preexposure and target training.
      The results are consistent with an account offered by the extended comparator
      hypothesis.

PMID- 19839704
TI  - Perception of food amounts by chimpanzees (Pan troglodytes): the role of
      magnitude, contiguity, and wholeness.
AB  - The authors investigated choice behavior by chimpanzees in five experiments
      involving choices between different amounts of food. Chimpanzees did not maximize
      the amount of food they obtained when choosing between a single 20-g banana piece
      and another option containing a 20-g piece and a 5-g piece. This was true even
      though they successfully discriminated between 20-g and 25-g banana pieces in
      other trials. When items in the mixed option were stacked, however, the
      chimpanzees chose the larger amount. Later experiments indicated that changing
      the magnitude of the two amounts did not change performance if the difference in
      magnitude between the two options remained the same (e.g., 40 g plus 10 g vs. 40
      g). However, chimpanzees did improve when the two-item option was increased in
      its magnitude relative to the single slice (e.g., 20 g plus 10 g vs. 20 g). These
      results indicated that chimpanzees undervalued the total amount of food in sets
      when items differed in size and did not appear to be whole. Another experiment
      confirmed that it was this notion of wholeness that evoked suboptimal responding
      because chimpanzees were successful in the same comparisons with a different type
      of food that appeared less fractionated when presented as two pieces. These
      results provide evidence of suboptimal responding in some natural choice
      situations that prevents chimpanzees from maximizing food intake.

PMID- 19839705
TI  - Stimulus dynamics and temporal discrimination: implications for pacemakers.
AB  - The purpose of the present study was to observe the functional relationship
      between stimulus dynamics and stimulus duration judgments in humans. Stimulus
      duration was defined as the length of time that a spinning sphere appeared on a
      computer screen. Stimulus dynamics were defined by how quickly the sphere rotated
      on its y-axis. Using a logarithmic scale, a psychophysical bisection task was
      used to divide stimulus durations into two categories, short and long. Across
      three experiments, participants' duration judgments were longer the faster the
      sphere was rotated. This effect was observed over both a long and short temporal
      scale and over a wide range of stimulus dynamics despite the fact that the
      reinforcement contingencies penalized participants for this effect. The results
      are discussed in terms of perceived change as the possible basis of temporal
      duration estimation. This hypothesis was investigated through applications of the
      leading quantitative models of temporal discrimination to the present data.

PMID- 19839706
TI  - Human sequence learning under incidental and intentional conditions.
AB  - This research explored the role that dissociable associative learning and
      hypothesis-testing processes may play in human sequence learning. Two 2-choice
      serial reaction time (SRT) tasks were conducted, 1 under incidental conditions
      and the other under intentional conditions. In both cases an experimental group
      was trained on 4 subsequences (i.e., XXX, XYY, YYX, and YXY). To control for
      sequential effects, sequence learning was assayed by comparing their performance
      to a control group that had been trained on a pseudorandom ordering, during a
      test phase in which both groups experienced effectively the same trial order.
      Under incidental conditions participants demonstrated learning of the
      subsequences that ended in an alternation, but not of those that ended in a
      repetition. In contrast, under intentional conditions XXX showed the greatest
      evidence of learning. This dissociation is explained using a 2-process model of
      learning, with an associative process (the augmented simple recurrent network
      [SRN]) capturing the incidental pattern, and a rule-based process explaining the
      advantage for XXX under intentional conditions.

PMID- 19839707
TI  - Discrimination and generalization along a simple dimension: peak shift and rule
      governed responding.
AB  - In 2 experiments, participants learned to discriminate between a pair of simply
      related, but very similar, colors in a 2-choice categorization task. They were
      then tested over a wider range of isoluminant hues. Over these test values, both
      experiments yielded a postdiscrimination gradient that was initially peak-shifted
      but became monotonic through the course of testing. In Experiment 2, the presence
      of this early peak shift and subsequent change in gradient form were related to
      participants' inability to verbally characterize the difference between the
      training stimuli. This suggests a transition from generalization based on simple
      physical similarity to generalization based on a "verbalizable" rule, as a
      consequence of additional relevant information becoming available during test. An
      explanation appealing to both associative and strategically controlled verbal
      processes provides an accurate account of the results.

PMID- 19839708
TI  - Conditioned inhibition in the spatial domain.
AB  - Using a variation on the standard procedure of conditioned inhibition (Trials A+
      and AX-), rats (Rattus norvegicus) in a circular pool were trained to find a
      hidden platform that was located in a specific spatial position in relation to 2
      individual landmarks (Trials A --> platform and B --> platform; Experiments 1a
      and 1b) and to 2 configurations of landmarks (Trials ABC --> platform and FGH -->
      platform; Experiment 2a). The rats also underwent inhibitory trials (Experiment
      1: Trials AZ --> no platform; Experiment 2a: Trials CDE --> no platform)
      interspersed with these excitatory trials. In both experiments, subsequent test
      trials without the platform showed both a summation effect and retardation of
      excitatory conditioning, and in Experiment 2a rats learned to avoid the CDE
      quadrant over the course of the experiment. Two further experiments established
      that these results could not be attributed to any difference in salience between
      the conditioned inhibitors and the control stimuli. All these results contribute
      to the growing body of evidence consistent with the idea that there is a general
      mechanism of learning that is associative in nature.

PMID- 19839709
TI  - "Causal reasoning" in rats: a reappraisal.
AB  - It has recently been argued that rats engage in causal reasoning and they do so
      in a way that is consistent with Bayes net theories (Blaisdell, Sawa, Leising &
      Waldmann, 2006). This argument was based upon the finding that the tendency of
      cues to elicit approach to a food-well was reduced when their presentation was
      contingent on lever pressing. There is, however, an alternative interpretation of
      the critical experimental findings that is based on the simple principle of
      response competition: wherein lever pressing interferes with the tendency to
      approach the food well. Here the authors replicated Experiments 1 and 2a of
      Blaisdell et al. (2006) and found reciprocal patterns of lever pressing and food
      well approach during the critical cues. These results lend direct support for an
      interpretation in terms of response competition while providing evidence contrary
      to Bayes net theories, and are readily interpreted within the theoretical
      framework provided by traditional associative learning theory.

PMID- 19839710
TI  - Eye movements during list execution reveal no planning in monkeys (Macaca
      fascicularis).
AB  - When trained on a serial-order task to respond to 5 simultaneously displayed
      stimuli, monkeys (Macaca fascicularis) show an elevated latency to respond to the
      first item (A) or the first 2 items (A and B) followed by short and uniform
      latencies to respond to the remaining items. This pattern has been interpreted as
      evidence of planning, with the long initial latency reflecting the animal
      planning their responses, and the subsequent short and uniform latencies
      reflecting the execution of the planned responses. An analysis of eye movements,
      however, revealed no evidence of planning. The elevated latency to item A is
      likely an artifact of the method of stimulus display.

PMID- 19839712
TI  - Preparation, characterization, and evaluation of gatifloxacin loaded solid lipid
      nanoparticles as colloidal ocular drug delivery system.
AB  - This article describes the preparation and characterization of solid lipid
      nanoparticles (SLNs) prepared with stearic acid (SLN-A) and a mixture of stearic
      acid and Compritol (SLN-B) as lipid matrix and poloxamer-188 as surfactant, using
      sodium taurocholate and ethanol as co-surfactant mixture, with a view to applying
      the SLN in topical ocular drug delivery. The SLNs were prepared by o/w
      microemulsion technique and characterized by time-resolved particle size
      analysis, polydispersity index, zeta(zeta)-potential, differential scanning
      calorimetry (DSC), IR-spectroscopy, and wide-angle X-ray diffractometry (WAXD).
      The results obtained in these studies were compared with SLN prepared with
      stearic acid alone. IR, WAXD, and DSC studies revealed low-crystalline SLN and
      were having positive zeta-potentials after three-months of storage. Results
      indicated mixed lipid-matrix produced SLN with low-crystallinity and smaller
      particle sizes and higher drug entrapment compared with SLN prepared with stearic
      acid alone, therefore SLN-B would be suitable for the preparation of
      nanosuspension. Nanosuspensions were subjected to rheological and physicochemical
      evaluation, in vitro drug release and ex vivo corneal permeation studies and
      their effect were evaluated on corneal hydration-level. SLN composed of stearic
      acid and compritol would prove to be a good ocular drug delivery system
      considering the smaller particle size, particle size stability, and
      physiologically tolerable components.

PMID- 19839713
TI  - Epicardial measurement of alterations in extracellular pH and electrolytes during
      ischemia and reperfusion in cardiac surgery.
AB  - Simultaneous measurements of extracellular pH, potassium (K(+)), and calcium
      (Ca(2+)) activity might be indicative of myocardium vitality or ischemia. Ten
      consecutive patients undergoing elective coronary artery bypass grafting were
      studied. Epicardial extracellular pH, potassium, and calcium were measured by a
      miniaturized disposable multi-sensor probe. Blood gases and electrolytes were
      derived with measurements of arterial and mixed venous blood samples at intervals
      during surgery. The mean epicardial baseline levels for pH in all patients were
      8.04+/-0.22 arbitrary units (AU) for the right ventricle (RV) and 8.03+/-0.21 AU
      for the left ventricle (LV); for Ca(2+) 0.23+/-0.07 mmol/l (RV) and 0.20+/-0.10
      mmol/l (LV); and for K(+) 4.54+/-1.51 mmol/l (RV) and 4.38+/-0.57 mmol/l (LV).
      Before ischemia, epicardial pH was moderately (p<0.05), and K(+), and Ca(2+) were
      closely correlated (p<0.001) with blood values. During reperfusion, epicardial
      measurements were weakly correlated (p<0.001) with blood values for pH, venous
      K(+) and Ca(2+), but moderately correlated with arterial K(+) and Ca(2+)
      (p<0.01). The measurements indicated intraoperative episodes of ischemia and
      reperfusion with reproducible trends of extracellular pH, K(+), and Ca(2+), which
      results in electrolyte patterns applicable for detecting inadequate myocardial
      protection during cardiac surgery in patients.

PMID- 19839714
TI  - [Structure design examinations of three-dimensional textile scaffolds employed
      for tissue engineering in vitro: a pilot study].
AB  - Postoperative apical growth of epithelium on teeth is a common complication of
      surgical periodontal therapy. Absorbable textile scaffolds, placed between the
      operated tooth and its nearby tissues, are considered to serve as a mechanical
      barrier and prevent undesired apical epithelial growth. They allow local
      regeneration and new formation of human gingival fibroblasts when the scaffolds
      are colonized with autologous cells. The aim of this study was to examine
      proliferation behavior of human gingival fibroblasts on polyglycolic acid (PGA)
      fleeces with various structural characteristics. The characteristics of the PGA
      fleeces varied as follows: thickness (1.0-5.0 mm), porosity (85-98%), area mass
      (56.6-166.9 g/m(2)), and texture. Proliferation of incorporated autologous cells
      was analyzed by determining the number of live cells, the total absorbed protein,
      and the degree of cell proliferation. Textile PGA fleeces seem to be suitable as
      scaffold structures for human gingival fibroblasts. Results showed that
      structural parameters of fleeces have a significant influence on cell
      proliferation. Our results showed that a fleece made from knit-de-knit fibers
      with a porosity of 90% and a thickness of 1.5 mm was most suitable as a scaffold
      structure and had the highest cell proliferation rate and was superior to fleeces
      with other structural characteristics.

PMID- 19839711
TI  - Conservation of telomere protein complexes: shuffling through evolution.
AB  - The rapid evolution of telomere proteins has hindered identification of orthologs
      from diverse species and created the impression that certain groups of eukaryotes
      have largely non-overlapping sets of telomere proteins. However, the recent
      identification of additional telomere proteins from various model organisms has
      dispelled this notion by expanding our understanding of the composition,
      architecture and range of telomere protein complexes present in individual
      species. It is now apparent that versions of the budding yeast CST complex and
      mammalian shelterin are present in multiple phyla. While the precise subunit
      composition and architecture of these complexes vary between species, the general
      function is often conserved. Despite the overall conservation of telomere protein
      complexes, there is still considerable species-specific variation, with some
      organisms having lost a particular subunit or even an entire complex. In some
      cases, complex components appear to have migrated between the telomere and the
      telomerase RNP. Finally, gene duplication has created telomere protein paralogs
      with novel functions. While one paralog may be part of a conserved telomere
      protein complex and have the expected function, the other paralog may serve in a
      completely different aspect of telomere biology.

PMID- 19839715
TI  - Factors that retard remyelination in multiple sclerosis with a focus on TIP30: a
      novel therapeutic target.
AB  - In the CNS oligodendrocytes produce myelin and ensheath individual axons after
      birth. Demyelination disables saltatory conduction and leads to loss of neural
      functions. Oligodendrocyte precursor cells (OPCs) are immature and abundant
      reservoir cells in the adult brain that are capable of differentiating into
      myelinating oligodendrocytes. Upon demyelination insults, OPCs are spontaneously
      induced to differentiate in order to remyelinate denuded axons and promote
      functional recovery. While remyelination is an efficient regenerative process in
      the CNS, it often fails in the chronic phase of multiple sclerosis (MS). OPCs are
      nonetheless preserved in many MS lesions, suggesting that arrested OPC
      differentiation underlies remyelination failure in chronic MS. Understanding the
      molecular pathology of this arrested differentiation and remyelination failure in
      chronic MS is critical for developing remyelination medicines that will promote a
      full functional recovery in these patients. Recently, TIP30 was identified as an
      inhibitor of OPC differentiation in MS. TIP30 inhibits proper nucleocytoplasmic
      transport and thus disables nuclear import of transcription factors that are
      required for differentiation. TIP30 may also increase susceptibility of OPCs to
      cell death. In this review, we examine the pathophysiological nature of
      remyelination failure in chronic MS and discuss the role of TIP30 as a novel
      therapeutic target.

PMID- 19839716
TI  - Targeting miR-205 in breast cancer.
AB  - As small non-coding regulatory RNAs, microRNAs are capable of silencing gene
      expression by translational repression or mRNA degradation. Accumulating evidence
      indicates that deregulation of microRNAs is often associated with human
      malignancies and suggests a causal role of microRNAs in neoplasia, presumably
      because microRNAs can function as oncogenes or tumor suppressors. Among them, miR
      205 is significantly underexpressed in breast tumors compared with matched normal
      breast tissue although miR-205 has been shown to be upregulated in some other
      type of tumors. Furthermore, breast cancer cell lines, including MCF-7 and MDA-MB
      231, express a lower level of miR-205 than the non-malignant MCF-10A cells.
      Ectopic expression of miR-205 significantly inhibits cell proliferation and
      anchorage-independent growth as well as cell invasion. These findings establish
      the tumor suppressive role of miR-205, which is probably through direct targeting
      of oncogenes such as ErbB3 and Zeb1. Therefore, miR-205 may serve as a unique
      therapeutic target for breast cancer.

PMID- 19839717
TI  - Increased HER2/neu expression in recurrent hormone receptor-positive breast
      cancer.

PMID- 19839718
TI  - Dickkopf-1 autoantibody is a novel serological biomarker for non-small cell lung
      cancer.
AB  - OBJECTIVE: We investigated whether or not there are autoantibodies for DKK1
      (Dickkopf-1) in patients with non-small cell lung cancer (NSCLC) and whether this
      autoantibody can be used for cancer detection. METHODS: The levels of DKK1
      autoantibodies were determined in 93 NSCLC patients and 87 healthy controls.
      RESULTS: We found that, in the sera, the presence of autoantibody against DKK1
      was highly correlated with NSCLC. High anti-DKK1 autoantibody titres were found
      in the sera of NSCLC patients, whereas low or negative titres were found in the
      control group. The ROC curve results showed that autoantibody immunoassay
      exhibited 62% sensitivity and 84% specificity. The sensitivity for the detection
      of NSCLC in stage I also reach 64.3%. Furthermore, a combined ELISA assays for
      both DKK1 and autoantibody DKK1 increased sensitivity and classified 81.7%
      (76/93) of the NSCLC patients as positive, whereas only 13.8 % (12/87) of healthy
      volunteers were falsely diagnosed as positive. CONCLUSIONS: Our results suggest
      that the detection of circulating DKK1 autoantibody could potentially serve as a
      useful non-invasive marker for determining lung cancer status.

PMID- 19839719
TI  - In vitro enhancement of SAOS-2 cell calcified matrix deposition onto radio
      frequency magnetron sputtered bioglass-coated titanium scaffolds.
AB  - In bone tissue engineering, bioglass coating of titanium (Ti) scaffolds has drawn
      attention as a method to improve osteointegration and implant fixation. In this
      in vitro study, bioactive glass layers with an approximate thickness of 1 microm
      were deposited at 200 degrees C onto a three-dimensional Ti-6Al-4V scaffold using
      a radio frequency (r.f.) magnetron sputtering system. After incubation with SAOS
      2 human osteoblasts, in comparison with the uncoated scaffolds, the bioglass
      coated scaffolds showed a twofold increase in cell proliferation (p < 0.05) up to
      68.4 x 10(6), and enhanced the deposition of extracellular matrix components such
      as decorin, fibronectin, osteocalcin, osteonectin, osteopontin, and type-I and 
      III collagens (p < 0.05). Calcium deposition was twofold greater on the bioglass
      coated scaffolds (p < 0.05). The immunofluorescence related to the preceding bone
      matrix proteins and calcium showed their colocalization to the cell-rich areas.
      Alkaline phosphatase activity increased twofold (p < 0.001) and its protein
      content was threefold higher with respect to the uncoated sample. Quantitative
      reverse transcriptase-polymerase chain reaction analysis revealed upregulated
      transcription specific for type-I collagen and osteopontin (p < 0.001). All
      together, these results demonstrate that the bioglass coating of the three
      dimensional Ti scaffolds by the r.f. magnetron sputtering technique determines an
      in vitro increase of the bone matrix elaboration and may potentially have a
      clinical benefit.

PMID- 19839720
TI  - In vitro and in vivo evaluation of osteogenesis of human umbilical cord blood
      derived mesenchymal stem cells on partially demineralized bone matrix.
AB  - The osteogenic differentiation potential of umbilical cord blood-derived
      mesenchymal stem cells (UCB-MSCs) has been documented previously, and partially
      demineralized bone matrix (pDBM) represents a promising candidate for bone tissue
      engineering scaffolds. In this study, pDBM scaffolds derived from porcine
      cancellous bone were evaluated for their ability to support human UCB-MSCs
      osteogenic differentiation in vitro and bone-forming capacity in vivo to assess
      the potential use of UCB-MSCs in bone tissue engineering applications. MSCs were
      isolated from full-term human UCB and expanded, and their cell surface antigen
      markers and multilineage capability to differentiate into osteoblasts,
      chondrocytes, and adipocytes were analyzed. The in vitro proliferation and
      osteogenic differentiation of UCB-MSCs loaded onto the three-dimensional pDBM
      scaffolds were determined. Critical-sized full-thickness circular defects (5 mm
      in diameter) created bilaterally in the parietal bones of athymic rats were
      treated with one of the following: osteogenically induced UCB-MSC/pDBM composites
      (Group A, n = 8), noninduced UCB-MSC/pDBM composites (Group B, n = 8), pDBM alone
      (Group C, n = 8), or left untreated (Group D, n = 8). Microcomputed tomography
      analysis showed that new bone was formed in Group A at 6 weeks postimplantation,
      and greater bone volume and density were found after 12 weeks. In other groups,
      new bone formation was not evident after 6 weeks, and no bone union was found at
      12 weeks. Histological examination revealed that the defect was repaired by
      tissue-engineered bone in Group A at 12 weeks, and fibrous union was observed in
      Groups B, C, and D. These results demonstrate that pDBM can support osteogenic
      differentiation of human UCB-MSCs in vitro and in vivo, and UCB-MSCs may serve as
      an alternative cell source for bone tissue engineering and regeneration.

PMID- 19839721
TI  - Platelet-derived growth factor receptor signaling is not involved in osteogenic
      differentiation of human mesenchymal stem cells.
AB  - Platelet-derived growth factor (PDGF) receptor signaling plays an important role
      in the regulation of proliferation and migration of skeletal cells such as
      osteoblasts or mesenchymal stem cells (MSCs). However, involvement of these
      receptors in the process of osteoblastic differentiation of MSCs is still a
      matter of debate. The aim of our study was to examine the role of PDGF receptor
      signaling in osteogenic differentiation of human MSCs. For this purpose, we
      performed PDGF receptor stimulation as well as inhibition experiments. Inhibition
      experiments were carried out with Tyrphostin AG1296, a potent and specific
      inhibitor of PDGF receptor activity. As expected, Tyrphostin AG1296 treatment
      caused a concentration-dependent decrease in fetal calf serum and PDGF-BB-induced
      proliferation of MSCs and effectively inhibited PDGF-BB-induced phosphorylation
      of extracellular-regulated kinase 1/2. However, PDGF receptor inhibition had no
      significant effect on osteoblastic differentiation of MSCs, as evaluated
      histochemically by von Kossa, Alizarin-Red, and osteocalcin stainings. Moreover,
      mineralized matrix production, as assayed by quantitative Ca(2+)-measurements,
      was also not modulated by Tyrphostin AG1296 treatment. These results were
      noticeable irrespective of whether MSCs were grown under nonosteogenic or
      osteogenic differentiation conditions. Similarly, PDGF-BB treatment of MSCs in
      receptor stimulation experiments also failed to modulate mineralization. However,
      expression of alkaline phosphatase was suppressed by Tyrphostin AG1296 treatment
      at later stages of osteogenesis but not in the early stages, as assessed by
      enzyme activity and mRNA expression assays. Expression of other osteogenic marker
      genes such as osteocalcin, runt-related transcription factor 2, osteopontin,
      collagen type I, and bone sialoprotein was almost unaffected in our perturbation
      studies. From these experiments, we conclude that PDGF receptor signaling
      sustains proliferation without affecting osteogenic differentiation of MSCs.

PMID- 19839722
TI  - Electrically mediated delivery of plasmid DNA to the skin, using a multielectrode
      array.
AB  - The easy accessibility of skin makes it an excellent target for gene transfer
      protocols. To take full advantage of skin as a target for gene transfer, it is
      important to establish an efficient and reproducible delivery system.
      Electroporation is a strong candidate to meet this delivery criterion.
      Electroporation of the skin is a simple, direct, in vivo method to deliver genes
      for therapy. Previously, delivery to the skin was performed by means of
      applicators with relatively large distances between electrodes, resulting in
      significant muscle stimulation and pain. These applicators also had limitations
      in controlling the directionality of the applied field. To resolve this issue, a
      system consisting of an array of electrodes that decreased the distance between
      them and that were independently addressable for directional control of the field
      was developed. This new multielectrode array (MEA) was compared with an
      established electrode. In a rat model, comparable reporter expression was seen
      after delivery with each electrode. Delivery was also evaluated in a guinea pig
      model to determine the potential of this approach in an animal model with skin
      thickness and structure similar to human skin. The results clearly showed that
      effective delivery was related to both the electrode and the parameters chosen.
      With the MEA, the muscle twitching associated with application of electric fields
      was notably reduced compared with conventional electrode systems. This is
      important, as it will facilitate the translation of electroporation-mediated gene
      delivery to skin for clinical use with DNA vaccines or for therapies for cancer
      or protein deficiencies.

PMID- 19839723
TI  - Induction of germline apoptosis by cobalt and relevant signal transduction
      pathways in Caenorhabditis elegans.
AB  - Many investigations showed that cobalt exposure could induce apoptosis both in
      cells and tissues. However, appropriate in vivo animal models to assess the
      underlying mechanisms of cobalt-induced apoptosis are currently unavailable. The
      model organism, Caenorhabditis elegans, has been shown to be a good model for
      evaluating many biological processes. This study detected significant cobalt
      induced germline cell apoptosis after 12-h exposure; thus demonstrating that C.
      elegans could be a mammalian in vivo substitute model to study mechanisms of
      apoptosis. Then knockout gene C. elegans strains were utilized to investigate the
      relationship between cobalt-induced apoptosis and relevant signal pathways, which
      were involved in DNA damage and repair, apoptosis regulation, and damage signal
      transduction. The results presented here demonstrated that cobalt-induced
      apoptosis was independent of the DNA damage response gene, such as hus-1, p53/cep
      1, and egl-1. The loss-of-function of the genes that related to JNK and p38 MAPK
      signaling cascades suppressed cobalt-induced germline apoptosis, while ERK
      signaling cascades have no effect on the cobalt-induced germline apoptosis.

PMID- 19839724
TI  - The influence of combinations of oximes on the reactivating and therapeutic
      efficacy of antidotal treatment of soman poisoning in rats and mice.
AB  - The influence of the combination of oximes on the reactivating and therapeutic
      efficacy of antidotal treatment of acute soman poisoning was evaluated. The
      ability of two combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to
      reactivate soman-inhibited acetylcholinesterase and reduce acute toxicity of
      soman was compared with the reactivating and therapeutic efficacy of antidotal
      treatment involving single oxime (HI-6, trimedoxime, K203) using in vivo model.
      Studies determining percent of reactivation of soman-inhibited blood and
      diaphragm acetylcholinesterase in poisoned rats showed that the reactivating
      efficacy of both combinations of oximes is slightly greater than the reactivating
      efficacy of the most effective individual oxime, but the difference among them is
      not significant. Both combinations of oximes were found to be as effective in the
      reduction of acute lethal toxic effects in soman-poisoned mice as the antidotal
      treatment involving the most efficacious individual oxime. Thus, the efficacy of
      oximes is comparative in rats vs mice. A comparison of reactivating and
      therapeutic efficacy of individual oximes showed that the newly developed oxime
      K203 is approximately as effective as commonly used trimedoxime; nevertheless,
      their reactivating and therapeutic efficacy is markedly lower compared to the
      oxime HI-6. Based on the obtained data, one can conclude that the antidotal
      treatment involving chosen combinations of oximes does not significantly
      influence the potency of the most effective individual oxime (HI-6) to reactivate
      soman-inhibited rat acetylcholinesterase and to reduce acute toxicity of soman.

PMID- 19839725
TI  - Drugs interfering with mitochondrial disorders.
AB  - OBJECTIVES: Treatment of mitochondrial disorders (MIDs) is a challenge, since
      there is no causal therapy available and since there are few studies available,
      which demonstrate an effect of any agents offered for symptomatic or supportive
      therapy. Treatment of MIDs is based on five main columns, including symptomatic
      measures, application of supportive agents, dietary measures, physiotherapy, and
      the avoidance of drugs known to be toxic for mitochondrial functions. This review
      aims to give an overview about those agents that interfere with mitochondrial
      functions. RESULTS: Mitochondrion-toxic agents include corticosteroids, valproic
      acid, phenytoin, barbiturates, propofol, volatile anesthetics, nondepolarizing
      muscle relaxants, some local anesthetics, statins, fibrates, biguanides,
      glitazones, beta-blockers, amiodarone, some neuroleptics, some antibiotics, some
      chemotherapeutics, nucleoside reverse transcriptase inhibitors, and various other
      drugs. These agents should be avoided or given only under close monitoring,
      although some of them also exhibit beneficial effects, possibly due to the
      peculiarities of mitochondrial genetics. Typical side effects may be steroid
      myopathy, propofol syndrome, statin/fibrate myopathy, neuroleptic-induced
      extrapyramidal signs, or zidovudine myopathy. CONCLUSIONS: Avoiding or
      discontinuing mitochondrion-toxic drugs in MID patients can have a significant
      impact on the course and outcome of these patients.

PMID- 19839726
TI  - Distinctive degradation behaviors of electrospun polyglycolide, poly(DL-lactide
      co-glycolide), and poly(L-lactide-co-epsilon-caprolactone) nanofibers cultured
      with/without porcine smooth muscle cells.
AB  - Biodegradable nanofibers have become a popular candidate for tissue engineering
      scaffolds because of their biomimetic structure that physically resembles the
      extracellular matrix. For certain tissue regeneration applications, prolonged in
      vitro culture time for cellular reorganization and tissue remodeling may be
      required. Therefore, extensive understanding of cellular effects on scaffold
      degradation is needed. There are only few studies on the degradation of
      nanofibers, and also the studies on degradation throughout cell culture are rare.
      In this study, polyglycolide (PGA), poly(DL-lactide-co-glycolide) (PLGA) and
      poly(L-lactide-co-epsilon-caprolactone) [P(LLA-CL)] were electrospun into
      nanofibrous meshes. The nanofibers were cultured with porcine smooth muscle cells
      for up to 3 months to evaluate their degradation behavior and cellular response.
      The results showed that the degradation rates are in the order of PGA >> PLGA >
      P(LLA-CL). PGA nanofibers degraded in 3 weeks and supported cell growth only in
      the first few days. PLGA nanofiber scaffolds facilitated cell growth during the
      first 30 days after seeding, but cell growth was slow thereafter. P(LLA-CL)
      nanofibers facilitated long-term (1-3 months) cell growth. mRNA quantification
      using real-time polymerase chain reaction revealed that some smooth muscle cell
      markers (alpha-actinin and calponin) and extracellular matrix genes (collagen and
      integrin) seemed to be downregulated with increased cell culture time. Cell
      culture significantly increased the degradation rate of PGA nanofibers, whereas
      the effect on PLGA and P(LLA-CL) nanofibers was limited. We found that the
      molecular weight of P(LLA-CL) and PLGA nanofibers decreased linearly for up to
      100 days. Half lives of PLGA and P(LLA-CL) nanofibers were shown to be 80 and 110
      days, respectively. In summary, this is the first study to our knowledge to
      evaluate long-term polymeric nanofiber degradation in vitro with cell culture.
      Cell culture accelerated the nanofibrous scaffold degradation to a limited
      extent. P(LLA-CL) nanofibers could be a good choice as scaffolds for long-term
      smooth muscle cell culture.

PMID- 19839727
TI  - Laparoscopic radical prostatectomy.

PMID- 19839728
TI  - Endoscopic urethroplasty using small intestinal submucosal patch in cases of
      recurrent urethral stricture: a preliminary study.
AB  - OBJECTIVES: The objective of this study was to evaluate the results of internal
      urethrotomy with endoscopically placed small intestinal submucosa (SIS) graft for
      treatment of selected cases of recurrent urethral stricture. PATIENTS AND
      METHODS: This prospective study included 10 patients with recurrent inflammatory
      bulbar urethral stricture of 0.5-2 cm in length with no dense spongiofibrosis.
      Following the 12 o'clock visual internal urethrotomy, a prepared 12F Foley's
      silicon catheter with the SIS patch was introduced into the urethra over a
      preplaced super-stiff guidewire. The advancement of this catheter was monitored
      via a 15F urethroscope to enable us to put its balloon with the overlying SIS
      patch at the site of the urethral incision. Thereafter, the balloon was inflated
      with saline and the catheter was secured with a silk suture to the glans. In
      addition, a suprapubic cystostomy was fixed for bladder drainage. These catheters
      were kept in place for 2 weeks. The patients were followed up at regular
      intervals using uroflowmetry and ascending urethrography. RESULTS: At 3-month
      follow-up, only two cases showed mild recurrent stricture and the rest of cases
      had a normally patent functional urethra. The subsequent follow-up studies of all
      the eight successful cases for 12-18 months revealed no evidence of recurrent
      stricture in all of them and no more interventions were required for any of them.
      On the other hand, the two cases with recurrent stricture showed a satisfactory
      response to regular monthly urethral dilatation. CONCLUSION: Endoscopic
      urethroplasty using SIS patch can be considered as a minimally invasive solution
      for cases with recurrent, short urethral stricture that are associated with mild
      spongiofibrosis.

PMID- 19839729
TI  - Pentoxifylline modulates p47phox activation and downregulates neutrophil
      oxidative burst through PKA-dependent and -independent mechanisms.
AB  - BACKGROUND AND AIM: Pentoxifylline (PTX) has been proven to be an inhibitor of
      fMLP-induced neutrophil (PMN) oxidative burst and is thought to function by
      increasing cAMP and Protein kinase A (PKA). We hypothesized that PTX diminishes
      production of the neutrophil respiratory burst by both PKA-dependent and
      independent mechanisms. MATERIAL AND METHODS: Human neutrophils were isolated and
      stimulated with fMLP (1microM) alone or in combination with PTX (2mM). PMN
      activation was determined by the cytochrome C reduction method in the presence
      and absence of p38 MAPK (SB203580), ERK (PD98059), and PKA inhibitors (H89).
      Western blot analysis of Ras, Raf, p38 MAPK, ERK, and Akt was performed in PMNs
      exposed to fMLP and PTX. Cell membranes were fractionated to measure membrane
      associated p47 phox. Treated cells were imaged using confocal microscopy to
      examine changes in localization of Akt and p47phox. RESULTS: PTX produced a
      decrease in oxidative burst that was diminished but not abrogated by H89
      exposure. The reduction in Ras, Raf, and Akt activation seen with PTX was not
      effected by the presence of H89. The ability of PTX to attenuate phosphorylation
      of p38 MAPK and ERK was significantly decreased in the presence of H89,
      suggesting a PKA-dependent mechanisms. Membrane fractions of neutrophils
      demonstrate that PTX decreased membrane-associated p47phox, thus diminishing the
      ability to generate oxidative burst. PTX also decreased membrane localization of
      Akt and p47phox by confocal microscopy. CONCLUSIONS: PTX attenuates activation of
      signaling molecules involved in activation of p47phox and suppress the subsequent
      assembly of the NADPH machinery through both PKA-dependent and PKA-independent
      mechanisms.

PMID- 19839730
TI  - Mitochondrial function determines the viability and osteogenic potency of human
      mesenchymal stem cells.
AB  - Advanced therapies medicinal products (ATMPs) have introduced innovative cell
      based products. However, the regulatory demands for characterization of ATMPs are
      currently unable to adequately address the safety of such products. As recent
      studies have emphasized the role of mitochondria in the osteogenic
      differentiation of human mesenchymal stem cells (hMSCs), we have studied in
      detail the viability and osteogenic differentiation potency of the hMSCs intended
      for use as ATMPs based on analyses of the mitochondrial inner membrane potential
      (DeltaPsi(m)). Flow cytometric measurement of 5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolcarbocyanine iodide (JC-1), propidium iodide fluorescence,
      and AnnexinV was employed to determine DeltaPsi(m), plasma membrane integrity,
      and organization of phosphatidylserine in plasma membrane, respectively, in
      cultured hMSCs. Apoptosis was induced by incubating cells at critical
      concentration (20 muM) of menadione. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) was used as an indicator for cell proliferation
      and alkaline phosphatase activity and calcium deposition as indicators of
      osteogenic differentiation. Based on JC-1 fluorescence, cell morphology,
      organization of phosphatidylserine, and plasma membrane integrity, we could sort
      cells into four categories that represented different cell quality. A strong
      correlation between JC-1 and osteogenic differentiation was demonstrated for the
      first time and thus this analytical tool is suitable not only to determine cell
      viability but also to predict osteogenic differentiation of hMSC.

PMID- 19839731
TI  - Adjuvant effect of aqueous extract of Rhodiola imbricata rhizome on the immune
      responses to tetanus toxoid and ovalbumin in rats.
AB  - In the present study we have evaluated the immunopotentiating activity of
      Rhodiola aqueous extract (RAE) in rats. The efficacy of RAE was determined by
      using strong antigen tetanus toxoid (TT) and weak antigen Ovalbumin (OVA). The
      dynamic changes in humoral and cell-mediated immune response were measured. The
      results indicated that the TT specific immunoglobulin levels were significantly
      enhanced by RAE and were at par with complete Freund's adjuvant (CFA). The level
      of OVA induced antibody response was also enhanced by RAE. It was observed that
      TT and OVA in combination with CFA or RAE could evoke a significant delayed type
      hypersensitivity (DTH) response, confirming its potential to generate strong cell
      mediated immunity (CMI). The anti-inflammatory or immunosuppressive effect of RAE
      was evaluated in adjuvant-induced arthritis model (AIA). RAE could not suppress
      the swelling response. Therefore, this study suggests that RAE has
      adjuvant/immunopotentiating activity in terms of humoral as well as cell-mediated
      immune response against strong antigen like TT and weak antigen like OVA.

PMID- 19839735
TI  - Localization of candidate genes in a region of high frequency of microvariant
      alleles for prostate cancer susceptibility: the chromosome region Yp11.2 genetic
      variation.
AB  - The Y chromosome has been suggested to play a role in prostate cancer (PCa)
      because the loss of this chromosome is the most common aberration in PCa. Study
      of short tandem repeats (STRs) could provide a means to rapidly scan genomes at
      known or unknown predisposing loci for some diseases. DNA samples from 281
      patients with PCa at the Portuguese Institute of Oncology, Porto, Portugal, and a
      population control of 175 healthy controls were analyzed for region Yp11.2 using
      AmpFlSTR Y-Filer kit (Applied Biosystems). The results demonstrated that
      microvariant alleles of DYS458 are overrepresented (p = 0.026). We found that
      allele 12 of DYS393 and allele 19 of DYS458 could have a protective effect (p =
      0.0051; odds ratio [OR] = 0.48; 95% confidence interval [95% CI] 0.27-0.38; and p
      = 0.0272; OR = 0.47; 95% CI 0.22-0.98). On the other hand, patients carrying
      allele 13 of DYS393 presented an increased risk to PCa (p = 0.015; OR = 1.97; 95%
      CI 1.26-3.07). These results are in concordance with the involvement of Y
      chromosome in PCa development. STR allele studies may add further information
      from the definition of a genetic profile of PCa resistance or susceptibility. As
      TSPY is located at region Yp11.2, this gene could play an essential role in PCa
      development.

PMID- 19839736
TI  - The two isomers of HDTIC compounds from Astragali Radix slow down telomere
      shortening rate via attenuating oxidative stress and increasing DNA repair
      ability in human fetal lung diploid fibroblast cells.
AB  - 4-Hydroxy-5-hydroxymethyl-[1,3]dioxolan-2,6'-spirane-5',6',7',8'-tetrahydro
      indolizine-3'-carbaldehyde (HDTIC)-1 and HDTIC-2 are two isomers extracted from
      Astragalus membranaceus (Fisch) Bunge Var. mongholicus (Bge) Hsiao. Our previous
      study had demonstrated that they could extend the lifespan of human fetal lung
      diploid fibroblasts (2BS). To investigate the mechanisms of the HDTIC-induced
      delay of replicative senescence, in this study, we assessed the effects of these
      two compounds on telomere shortening rate and DNA repair ability in 2BS cells.
      The telomere shortening rates of the cells cultured with HDTIC-1 or HDTIC-2 were
      31.5 and 41.1 bp with each division, respectively, which were much less than that
      of the control cells (71.1 bp/PD). We also found that 2BS cells pretreated with
      HDTIC-1 or HDTIC-2 had a significant reduction in DNA damage after exposure to
      200 microM H(2)O(2) for 5 min. Moreover, the 100 microM H(2)O(2)-induced DNA
      damage was significantly repaired after the damaged cells were continually
      cultured with HDTIC for 1 h. These results suggest that HDTIC compounds slow down
      the telomere shortening rate of 2BS cells, which is mainly due to the biological
      properties of the compounds including the reduction of DNA damage and the
      improvement of DNA repair ability. In addition, the slow down of telomere
      shortening rate, the reduction of DNA damage, and the improvement of DNA repair
      ability induced by HDTIC may be responsible for their delay of replicative
      senescence.

PMID- 19839737
TI  - SLP-2 overexpression is associated with tumour distant metastasis and poor
      prognosis in pulmonary squamous cell carcinoma.
AB  - OBJECTIVE: To investigate the role of stomatin-like protein 2 (SLP-2), a novel
      cancer-related gene, in pulmonary squamous cell carcinoma (PSCC) and its
      implications. METHODS: Immunohistochemical detection of SLP-2 was performed on 96
      cases of PSCC with a tissue microarray. RESULTS: SLP-2 was overexpressed in lung
      cancer compared with normal lung tissue (p <0.001). High-level SLP-2 expression
      was significantly correlated with distant metastasis (p = 0.025), decreased
      overall survival (p = 0.018) and disease-free survival (p = 0.017). SLP-2
      overexpression was an independent prognostic factor in multivariate analysis
      using the Cox regression model (p <0.05). CONCLUSION: SLP-2 overexpression is
      associated with tumour distant metastasis and poor prognosis in PSCC. SLP-2 could
      be regarded as a new significant prognostic biomarker for patients with PSCC.

PMID- 19839740
TI  - Properties of hepatocyte-like cell clusters from human adipose tissue-derived
      mesenchymal stem cells.
AB  - There are only a few reports that describe the hepatocytic differentiation
      potential of human adipose tissue-derived mesenchymal stem cells (hADMSCs) and no
      reports that describe the in vivo functions of hepatocyte-like cells
      differentiated from somatic stem cells including hADMSCs. In this study, we
      established a new method for generation of functional hepatocyte-like cell
      clusters using floating culture method and induced functional hepatocyte-like
      cell clusters, which functioned effectively not only in vitro but also in vivo.
      The generated hepatocyte-like cell clusters were characterized by gene expression
      analysis, functional assays, and transplantation into non-obese diabetic severe
      combined immunodeficiency (NOD-SCID) mouse with chronic liver injury. The
      generated hepatocyte-like cell clusters expressed various genes normally found on
      mature hepatocytes. The cell clusters exhibited functional characteristics of
      hepatocytes: they expressed albumin, secreted urea, had cytochrome P450 activity,
      could take up low-density lipoprotein, and stored glycogen. Transplantation of
      these cell clusters into NOD-SCID mouse with chronic liver injury resulted in a
      significant improvement of serum albumin and total bilirubin levels. In summary,
      we established a new protocol for efficient induction of hADMSCs into functional
      hepatocyte-like cell clusters.

PMID- 19839739
TI  - Treatment of malignant pleural effusion: PleuRx catheter or talc pleurodesis? A
      cost-effectiveness analysis.
AB  - INTRODUCTION: Malignant pleural effusions (MPEs) complicate many advanced
      malignancies and the median prognosis for those who develop MPEs is 6 months.
      These effusions lead patients to suffer from significant dyspnea, which may
      consequently impair mobility and lead to reduced quality of life. There are
      several treatment options for those with MPE. Thoracentesis may be quick and
      relatively easy to perform, but has a high recurrence rate; chest tube placement
      with talc slurry is quite effective at achieving pleurodesis, but this procedure
      can be quite painful and requires hospitalization. An alternative option is
      outpatient placement of the Pleurx catheter (Denver Biomedical Inc., Denver, CO)
      for home-based drainage of effusions. OBJECTIVE: To determine the incremental
      cost effectiveness of treating MPE with talc pleurodesis versus placement of
      Pleurx catheter. METHODS: We used decision analysis to compare treatments for the
      management of MPE. Cost data for Pleurx and talc treatments were obtained using
      Medicare reimbursement data for 2008, and outcome data (probability of treatment
      success and/or complication, and utility of health states) were obtained through
      literature review. RESULTS: Under our base-case analysis, treatment with talc was
      less costly than Pleurx (talc, $8170.80; Pleurx, $9011.60) with similar
      effectiveness (talc, 0.281 quality adjusted life years [QALYs]; Pleurx, 0.276
      QALYs). Pleurx became more cost effective (<$100K/QALY) when life expectancy was
      6 weeks or less. CONCLUSION: The treatment choice (talc pleurodesis or Pleurx
      catheter) for those with an MPE and a prognosis of 6 months should be based on
      the clinical situation and patient preferences, as well as local expertise and
      success rates of the procedures. A prospective study specific to the palliative
      care population might help to clarify which treatment is more cost effective in
      this population in which optimizing quality of life is essential.

PMID- 19839741
TI  - Cryopreservation does not affect the stem characteristics of multipotent cells
      isolated from equine peripheral blood.
AB  - Mammalian adult stem cells show, in vitro, extensive differentiative ability and
      may represent a versatile tool for tissue regenerative purposes, even after long
      term storage. Multipotent stem cells isolated from horse blood have been shown to
      possess the capacity to differentiate into diverse mesenchymal lineages although
      their full characterization is still at an early stage. The aim of this study was
      to examine the effects of cryopreservation on stemness characteristics of adult
      equine mesenchymal stem cells isolated from peripheral blood (ePB-MSC). Each
      sample of ePB-MSC was analyzed immediately and then after being frozen in liquid
      nitrogen for 10-12 months. After cryopreservation, cells conserved their
      morphology, alkaline phosphatase positivity, telomerase activity, karyotype
      profile, proliferation rate, and CD expression pattern. We characterized ePB-MSC
      as cells expressing CD44, CD90, CD117, and CD13, but not CD34 and CD45. Finally,
      freezing and storing ePB-MSC did not change their adipogenic, osteogenic, and
      myogenic differentiative potential, as analyzed by histochemistry,
      immunofluorescence, and polymerase chain reaction expression analyses. Overall,
      our results demonstrate that cryopreservation of ePB-MSC provides a convenient
      tool for in vitro applications, because cryopreserved cells possess the same stem
      characteristics as freshly isolated cells. Moreover, the feasibility of
      maintaining stem cell features of ePB-MSC after long-term storage has important
      implications for autologous cellular-based therapy in veterinary medicine.

PMID- 19839742
TI  - Evaluation of polyvinylpyrrolidone as a cryoprotectant for adipose tissue-derived
      adult stem cells.
AB  - The objective of this study was to test the hypothesis that human adipose tissue
      derived adult stem cells (ASCs) can be effectively cryopreserved and stored in
      liquid nitrogen using a freezing medium containing a high-molecular-weight
      polymer, polyvinylpyrrolidone (PVP), as the cryoprotective agent (CPA) instead of
      dimethylsulfoxide (DMSO). To this end we investigated the postfreeze/thaw
      viability and apoptotic behavior of passage 1 ASCs cryopreserved in 15 different
      media: (i) the traditional media containing Dulbecco's modified Eagle's medium
      (DMEM) with 80% fetal calf serum (FCS) and 10% DMSO; (ii) DMEM with 80% human
      serum (HS) and 10% DMSO; (iii) DMEM with various concentrations (1%, 5%, 10%,
      20%, and 40%) of PVP as the sole CPA; (iv) DMEM with PVP (5%, 10%, and 20%) and
      HS (10%); (v) DMEM with PVP (5%, 10%, and 20%) and FCS (10%); and (vi) DMEM with
      PVP (10%) and FCS (40% and 80%). Approximately 1 mL (10(6) cells/mL) of passage 1
      ASCs were frozen overnight in a -80 degrees C freezer and stored in liquid
      nitrogen for 2 weeks before being rapidly thawed in a 37 degrees C water bath (1
      2 min of agitation), resuspended in culture media, and seeded in separate wells
      of a six-well plate for a 24-h incubation period at 37 degrees C. After 24 h, the
      thawed samples were analyzed by bright-field microscopy and flow cytometry. The
      results suggest that the absence of DMSO significantly increases the fraction of
      apoptotic and/or necrotic ASCs. However, the percentage of viable cells obtained
      with 10% PVP and DMEM was comparable with that obtained in freezing media with
      DMSO and serum (HS or FCS), that is, approximately 70% + or - 8% and
      approximately 83% + or - 8%, respectively. Slightly enhanced cell viability was
      observed with the addition of serum (either HS or FCS) to the freezing media
      containing PVP as the CPA. Adipogenic and osteogenic differentiation behaviors of
      the frozen thawed cells were also assessed using histochemical staining and
      optical density measurements and the expression of adipogenic-associated genes
      was analyzed using reverse transcription-polymerase chain reaction. Our results
      suggest that after thawing, ASC viability and adipogenic and osteogenic
      differentiation abilities can be maintained even when ASCs are frozen in the
      absence of serum but with 10% PVP in DMEM.

PMID- 19839743
TI  - A study of HIV provider attitudes toward HLA-B 5701 testing in the United States.
AB  - Screening for HLA-B 5701 reduces the risk of developing an abacavir
      hypersensitivity reaction (ABC HSR) and is recommended in all patients before
      initiating highly active antiretroviral therapy (HAART) with abacavir. Between
      September 2007 and March 2008 we conducted a study of the attitudes and practice
      patterns of HIV providers in the United States to identify barriers to HLA-B 5701
      testing in clinical practice. Study participants who completed an educational
      program could receive HLA-B 5701 test kits for use in their clinical practice.
      Surveys were administered before and after the educational program. A total of
      477 HIV providers registered to participate in the survey, and 134 providers
      tested a total of 874 HIV-infected subjects, of which 6% (49/874) were HLA-B 5701
      positive. Of 433 providers who completed the preeducation survey, 97% indicated
      that the test provided clinical value and 77% anticipated barriers to testing,
      with cost/reimbursement the most frequently cited. Among 202 providers who
      completed the posteducation survey, perceptions of the test's value remained
      largely unchanged while the proportion of providers who anticipated or
      encountered barriers to testing decreased. Of providers who used HLA-B 5701 test
      kits, 86% (115/134) found it "very easy" or "easy" to obtain test results, 95%
      (127/134) found it "very easy" or "easy" to interpret results, and 89% (119/134)
      indicated that they planned to continue HLA-B 5701 testing after the study. The
      results of this study suggest that HLA-B 5701 testing is easy to use in clinical
      practice and is a valuable tool to help reduce the risk of developing ABC HSR.

PMID- 19839744
TI  - Impact of posterior rhabdosphincter reconstruction during robot-assisted radical
      prostatectomy: retrospective analysis of time to continence.
AB  - BACKGROUND AND PURPOSE: Posterior rhabdosphincter (PR) reconstruction during
      robot-assisted radical prostatectomy (RARP) was introduced in an attempt to
      improve postoperative continence. In the present study, we evaluate time to
      achieve continence in patients who are undergoing RARP with and without PR
      reconstruction. METHODS: A prospective RARP database was searched for most recent
      cases that were accomplished with PR reconstruction (group 1, n = 69) or with
      standard technique (group 2, n = 63). We performed the analysis applying two
      definitions of continence: 0 pads per day or 0-1 security pad per day. Patients
      were evaluated by telephone interview. Statistical analysis was carried out using
      the Kaplan-Meier method and log-rank test. RESULTS: With PR reconstruction,
      continence was improved when defined as 0-1 security pad per day (median time of
      90 vs 150 days; P = 0.01). This difference did not achieve statistical
      significance when continence was defined as 0 pads per day (P = 0.12).
      CONCLUSIONS: A statistically significant improvement in continence rate and time
      to achieve continence is seen in patients who are undergoing PR reconstruction
      during RARP, with continence defined as 0-1 security/safety pad per day. A
      larger, prospective and randomized study is needed to better understand the
      impact of this technique on postoperative continence.

PMID- 19839745
TI  - Outcome of simultaneous transurethral resection of bladder tumor and
      transurethral resection of the prostate in comparison with the procedures in two
      separate sittings in patients with bladder tumor and urodynamically proven
      bladder outflow obstruction.
AB  - BACKGROUND AND PURPOSE: A prospective randomized study was undertaken wherein
      transurethral resection of bladder tumor (TURBT) was performed along with
      transurethral resection of the prostate (TURP) in the same sitting (group A) in
      patients with bladder tumor and urodynamically proven bladder outflow
      obstruction. The outcome (recurrence and progression of superficial transitional
      cell carcinoma) was compared with patients who underwent TURBT and TURP in two
      separate sittings (group B) approximately 6 months apart. PATIENTS AND METHODS:
      Between January 2002 and December 2007, 48 patients were randomized for this
      study. The inclusion and exclusion criteria are described below. The patients
      were followed up according to standard protocols. The two groups were compared
      for the recurrence and progression of the bladder tumor. RESULTS: Mean age in
      both the groups were similar (group A = 56.06 +/- 4.45 years, group B = 57.36 +/-
      3.65 years). The mean duration of follow-up was also similar between the two
      groups (group A, 35.71 +/- 12.8 months; group B, 37.55 +/- 14.12 months; P >
      0.05). In group A, 12 (50%) patients had recurrence, while in group B, 11
      (42.85%) patients had recurrence. The differences in recurrence, mean elapsed
      time to recurrence, and progression of tumor between the two groups were
      statistically insignificant. CONCLUSION: TURBT and TURP can be performed
      simultaneously without any increased risk of recurrence and progression of tumor,
      if performed in a properly selected group of patients.

PMID- 19839747
TI  - Bordetella pertussis and pertussis vaccines.
AB  - Bordetella pertussis is a human-specific pathogen that causes whooping cough. The
      use of pertussis whole-cell vaccines in infants and toddlers led to decreased
      circulation of the bacterium in the child population and a marked decrease in the
      incidence of the disease. However, vaccine does not result in life-long immunity;
      indeed, the circulation of the bacterium has not been controlled in the adult
      population. Universal adult booster immunization is now possible using pertussis
      acellular vaccines, which target-and are thus likely to control-the virulence of
      this bacterium.

PMID- 19839748
TI  - Feasibility of right and left transvaginal retroperitoneal nephrectomy: from the
      porcine to the cadaver model.
AB  - PURPOSE: Minimally invasive nephrectomy performed through a natural orifice such
      as the vagina could enhance cosmesis and improve patient acceptance of the
      procedure and postoperative recovery. As the vagina has already been proposed as
      a site of specimen extraction in patients undergoing laparoscopic nephrectomy,
      the aim of this study was to explore the feasibility of transvaginal,
      retroperitoneal natural orifice transluminal endoscopic surgery (NOTES)
      nephrectomy for both left- and right-sided kidneys initially in a porcine model
      and thereafter in a human cadaver model. MATERIALS AND METHODS: Ten female pigs
      underwent NOTES nephrectomy (five having a left nephrectomy and five having right
      nephrectomy). To do this, each pig was anesthetized and placed in a supine
      position. A retroperitoneal conduit was established by means of a posterior
      colpotomy and the retroperitoneal space then entered with a conventional double
      channel endoscope (Storz). Thereafter, careful blunt dissection allowed a passage
      to be created up to the renal vessels and proximal ureter which were then
      dissected and divided separately after endoscopic clipping. We then attempted to
      reproduce the technique in two formaldehyde-preserved female cadavers. RESULTS:
      All the porcine procedures were accomplished by a totally NOTES approach with a
      mean operative time of 50 minutes (range 45-60). No bleeding or injury to any of
      the retroperitoneal structures occurred. In the two cadavers, the retroperitoneal
      access was reproduced, but a complete dissection of the kidney was not possible
      because of the rigor of the surrounding tissues. CONCLUSIONS: Transvaginal
      retroperitoneal NOTES right and left nephrectomy is certainly accomplishable in
      the porcine model, and the feasibility of the access was confirmed in two
      cadavers. As a retroperitoneal transvaginal dissection preserves the peritoneum
      and obviates bowel handling, this work should encourage further development of
      NOTES accesses for renal surgery.

PMID- 19839749
TI  - Contemporary different patterns of indications and outcomes for the surgical
      management of renal tumors in an academic center.
AB  - PURPOSE: Inconsistencies have been pointed out in the treatment of small renal
      tumors by laparoscopists, as many would remove the entire kidney unnecessarily,
      whereas open surgeons are more likely to perform partial nephrectomy. Thus, we
      compared the practice and outcomes between two groups of surgeons treating renal
      tumors. MATERIALS AND METHODS: We reviewed the renal cancer database from our
      institution from January 2000 to October 2006 for data retrieval and analysis.
      The patients treated by the laparoscopy staff (LS) and the oncology staff (OS)
      were divided into two groups for comparison. Data were collected for age, gender,
      type of surgery performed, time of operation, length of stay in the hospital,
      complications, histological evaluation, operation room time, hospital stay time,
      complications rate, and overall survival. RESULTS: A total of 240 patients were
      evaluated, 149 in the LS group (62%) and 91 in the OS group (38%), and the
      results have been summarized. Fifty percent of all procedures were open; however,
      in the OS group 100% of the surgeries were open and in the LS group 19% of the
      cases were open. Interestingly, only 9% of the surgeries in the OS group were
      nephron sparing, whereas in the LS group 60% of the patients had their kidneys
      spared. OS treated a higher percentage of locally advanced tumors. CONCLUSIONS:
      Laparoscopists performed a more variety of surgical approaches including open
      procedures and performed much more nephron sparing surgeries than the
      oncologists. Open surgery still plays an important role for locally advanced
      disease and hilar tumors.

PMID- 19839752
TI  - Association of TLR4 single-nucleotide polymorphisms and sarcoidosis in Greek
      patients.
AB  - The present study investigates the potential role of Toll-like receptor 4 (TLR4)
      Asp299Gly and Thr399Ile single-nucleotide polymorphisms (SNPs) as risk factors in
      the development of sarcoidosis using a novel high-throughput microtiter well
      based bioluminometric genotyping assay. One hundred and nineteen Greek patients
      with sarcoidosis and 209 control subjects were genotyped for the two SNPs of the
      TLR4 gene. The genotypes observed were in Hardy-Weinberg equilibrium. The
      heterozygote frequency for both SNPs in sarcoidosis group and control population
      was 13.4% (16/119) and 10.5% (22/209), respectively. The minor genotype was found
      to be the same for both sarcoidosis and control groups and similar to that found
      in other Caucasian populations. No significant association of Asp299Gly and
      Thr399Ile polymorphisms with increased susceptibility to sarcoidosis was found (p
      = 0.61 and odds ratio = 1.183). In conclusion, genotype data for the TLR4
      Asp299Gly and Thr399Ile polymorphisms in the Greek population were found to be in
      linkage disequilibrium, and no contribution in the pathogenesis of sarcoidosis
      was established. Further, in course of the present study, we demonstrated a very
      simple and sensitive high-throughput bioluminometric assay for genotyping
      Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene.

PMID- 19839753
TI  - Identification of four novel EXT1 and EXT2 mutations in five Chinese pedigrees
      with hereditary multiple exostoses.
AB  - Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder
      most frequently caused by the EXT1 and EXT2 gene mutations resulting in reduction
      or absence of heparan sulfate (HS) in the exostotic cartilage cap. In this study,
      we investigated the molecular defects in five Chinese pedigrees with HME by
      direct sequencing analysis. Two novel EXT1 gene mutations and two novel EXT2 gene
      mutations were identified in two and three pedigrees, respectively. Of the four
      mutations identified, the c.651-664delinsTTT and c.680delG mutations in the exon
      1 of EXT1 gene would cause frameshift (K218fs and R227fs) and introduce premature
      stop codon at amino acid site 220 and 251, respectively. The two missense
      mutations of c.398T > G in exon 2 and c.1016G > A in exon 6 of EXT2 gene result
      in the Leu133Arg and Cys339Tyr substitution, respectively. As HME is caused by
      defects in HS synthesis that is a complex process and not fully understood, these
      naturally occurring EXT mutations may provide important clues to future studies
      elucidating how EXT proteins contribute to HS biosynthesis.

PMID- 19839754
TI  - MTHFR C677T and factor V Leiden in recurrent pregnancy loss: a study among an
      endogamous group in North India.
AB  - AIM: In our study an attempt has been made to find the prevalence of genetic
      thrombophilia in recurrent pregnancy loss (RPL). METHODS: Methylene
      tetrahydrofolate reductase C677 (MTHFR C677T) and factor V Leiden (FVL) were
      investigated in 84 Rajput women with two or more pregnancy losses and in 80 age-
      and ethnicity-matched healthy controls. Restriction digestions of polymerase
      chain reaction product with HinfI and Mnl I were used for MTHFR C677T and FVL
      polymorphism detection, respectively. RESULTS: MTHFR C677T mutation was found in
      9/84 patients (10.71%) and 2/80 controls (2.5%), yielding an odds ratio (OR) for
      RPL related to MTHFR C677T of 4.68 (95% confidence interval [CI] = 0.98-22.37; p
      = 0.03). FVL was found in 4/84 patients (4.76%) and none among the controls,
      yielding a modified OR for RPL related to FVL of 9.00 (95% CI = 0.48-169.9; p =
      0.05). Both, MTHFR C677T and FVL were not found to be significantly more
      prevalent in patients than controls as a whole. However, MTHFR C677T showed
      significant association with early pregnancy loss (OR = 6.3; 95% CI = 1.22-32.85;
      p-value = 0.03; Bonferroni-corrected p-value = 0.04). CONCLUSIONS: Our study
      supports the association between MTHFR C677T and patients with early RPL among
      north Indian Rajputs and strengthens the notion that thrombophilia plays a role
      in this clinical entity.

PMID- 19839755
TI  - Identification of deletion carriers in X-linked chronic granulomatous disease by
      real-time PCR.
AB  - Chronic granulomatous disease (CGD) is a rare primary immunodeficiency affecting
      the innate immune system. Even if functional tests address the diagnosis of CGD,
      the identification of a molecular defect is essential for counselling family
      members at risk for being CGD carriers and for prenatal diagnosis. The X-linked
      form occurs in 65% of CGD patients. It is due to mutations in the CYBB gene, up
      to 12% of which are caused by large deletions. CGD carriers are usually healthy,
      and molecular analysis is essential to reveal their carrier status. The aim of
      this study was to apply a gene dosage approach, using SYBR green quantitative
      real-time polymerase chain reaction (RT-PCR), to quantify the genomic copy number
      in carriers and noncarriers of gross deletions covering the region of the CYBB
      gene. We studied the expression of two different amplification products of the
      CYBB gene, and the results confirmed a highly reduced expression of the gene in
      the carrier samples. The results were confirmed by linkage analysis and
      fluorescence in situ hybridization. Quantitative real-time PCR is fast and simple
      to perform, and we propose it as a new routine diagnostic approach to detect CGD
      carriers of deletions covering the region spanning the CYBB gene.

PMID- 19839756
TI  - Population severance in manipur at dopamine receptor D2 locus.
AB  - INTRODUCTION: Tibeto-Burman language-speaking Mongoloid groups of northeast India
      are reported to be genetically highly heterogeneous. Manipur, one of the states
      of this region sharing a major International border with Myanmar, is also
      expected to be diversified as seen by its large number of tribal and nontribal
      groups. A number of genomic markers, that is, autosomal, mitochondrial, and Y
      chromosomal ones, have been used to understand the peopling of the northeast
      region. AIMS: In this article, an attempt is made to understand the peopling of
      Manipur using three sites (Taq1A, Taq1B, and Taq1D) on the dopamine receptor D2
      (DRD2) gene through allele and haplotype frequencies and their distribution
      patterns. METHODS: In total, 367 blood samples were collected from eight
      populations of which three (Meitei, Muslims, and Bamon) are nontribal groups and
      five (Aimol, Kabui, Paite, Kom, and Thadou) are tribal groups. RESULTS: All the
      three sites are polymorphic in all the studied populations with relatively lower
      heterozyosities indicating a genetic discontinuity between the populations of
      mainland India and northeast India, suggesting the unlikeliness of eastward
      migration of people from Africa through India. CONCLUSION: High heterogeneity and
      predominance of ancestral haplotype (B2D2A1) among the Meitei suggest an
      admixture of incoming mongoloid groups with an already existing protoastroloid
      element. The study also highlights the distinctiveness of Manipuri population
      groups with respect to DRD2 gene polymorphism.

PMID- 19839757
TI  - Preliminary results in a study regarding the relationship between perlecan gene
      polymorphism and spinal muscular atrophy type I disease.
AB  - Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by
      weakness and atrophy of proximal muscles. Despite the fact that the disease
      transmission suggests an autosomal recessive trait, the wide spectrum of clinical
      manifestations indicates that other genes may contribute to the SMA phenotype. To
      identify possible modifier genes, the aim of our study was to investigate the
      relationship between BamH1 perlecan gene polymorphism and SMA type I, the
      classical severe form of the disease. We genotyped 40 patients with SMA type I
      disease and 50 subjects without personal or heredo-colateral neuromuscular
      problems, using the polymerase chain reaction-restriction fragment length
      polymorphism method. After statistical analysis of the observed genotypes, a
      significant difference (p = 0.03) could be observed regarding the incidence of TT
      genotype and T allele in boys with SMA type I compared with affected girls.
      However, this result cannot be assessed because of the small and unequal number
      of subjects. We concluded that there might be no association between perlecan
      gene polymorphism and SMA type I disease.

PMID- 19839758
TI  - Mutational Analysis of the alpha-L-iduronidase gene in three Egyptian families:
      identification of three novel mutations and five novel polymorphisms.
AB  - Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder that
      results from a deficiency in alpha-L-iduronidase (IDUA), which is involved in the
      degradation of dermatan and heparan sulfates. MPS I has three clinical
      phenotypes, ranging from the severe Hurler form to the milder Scheie phenotype.
      In this study, mutational analysis of the IDUA gene in three unrelated Egyptian
      families with Hurler phenotype was performed by sequencing the IDUA exons and
      exon-intron boundaries. Three novel mutations (c.854delC in exon 6, T141S in exon
      4, and IVS2+6c>t) and the previously reported G51D in exon 1 were detected. In
      addition, nine sequence variants, including five previously unreported
      polymorphisms (N73H, N297N, R363S, IVS10 (3025) g>t, and IVS11 (3318) c>a), were
      identified. This is the first report of IDUA mutations in Egyptian patients with
      MPS I. Our study showed a heterogeneous pattern of mutations and polymorphisms
      among Egyptian patients.

PMID- 19839759
TI  - Campylobacter excreted into the environment by animal sources: prevalence,
      concentration shed, and host association.
AB  - An intensive study of 443 isolates of Campylobacter jejuni and Campylobacter coli
      from 2031 fecal samples excreted by animal sources including cattle, sheep, and
      pigs, a range of wild and domesticated avian species and pets is described. The
      prevalence found in the majority of animal sources ranged from 22% to 28% with
      poultry being highest at 41% and cats and dogs lowest (<5%). The average count
      excreted for each animal source was found not to be significantly different
      ranging from approximately 10(2) to 10(5) cfu/g. Multilocus sequence typing
      (MLST) identified phylogenies that exhibited host specificity. A number of clonal
      complexes (CCs) and sequence types (STs) were characteristic of particular hosts
      (e.g., CC-179, ST-637, and ST-1341 found only in pigeons and gulls). Analysis of
      genetic distance demonstrated numerous significant differences in the
      distribution of MLST types (CC, ST, and allele) between animal sources. Host
      association was quantified using structure that correctly assigned the nine
      animal sources with accuracies of 28%, 24%, and 55% at the CC, ST, and allele
      levels, respectively. This is substantially higher than would be expected by
      random allocation (11%) but farmyard poultry had the lowest assignment accuracy
      (13%, 13%, and 21%) suggesting that isolates were shared with a wide range of
      other animals. This study demonstrates the link between MLST type and host and
      provides data that can be used in risk assessment and food attribution models.
      Further, it demonstrates the applicability of MLST to characterize Campylobacter
      strains from a broad range of environmental sources.

PMID- 19839761
TI  - Microbiological quality and safety of raw milk and soft cheese and detection of
      autochthonous lactic acid bacteria with antagonistic activity against Listeria
      monocytogenes, Salmonella Spp., and Staphylococcus aureus.
AB  - This study aimed to characterize the microbiological quality and safety of raw
      milk and soft cheese, verifying possible associations between microbial
      populations, and the detection of lactic acid bacteria (LAB) with antagonistic
      activity against foodborne pathogens. Raw milk (n = 36) and soft cheese (n = 18)
      samples were collected and submitted for the analysis of mesophilic aerobes,
      total coliforms, Escherichia coli, LAB, coagulase-positive Staphylococcus (CPS),
      Listeria monocytogenes, and Salmonella spp. In all, 389 LAB isolates were
      randomly selected and submitted for antagonistic tests against L. monocytogenes,
      St. aureus, Salmonella Typhimurium, and Lactobacillus sakei. The samples
      presented high counts of mesophilic aerobes, total coliforms, and LAB, and also
      high and significant correlation indices between these populations. Low levels of
      CPS and E. coli were observed, as well as an absence of Salmonella spp. and L.
      monocytogenes. A substantial portion of the analyzed samples presented LAB
      cultures with antagonistic activity, but not against Salmonella Typhimurium. The
      obtained results indicate the antimicrobial potential of the autochthonous
      microbiota of raw milk and soft cheese. Despite the spoilage potential, the LAB
      present in the studied food products can be isolated and properly characterized
      as antagonistic cultures, to be used in bioconservation studies for pathogen
      control in foods.

PMID- 19839760
TI  - Detection of Escherichia coli enteropathogens by multiplex polymerase chain
      reaction from children's diarrheal stools in two Caribbean-Colombian cities.
AB  - Acute diarrheal disease is a leading cause of childhood morbidity and mortality
      in the developing world and Escherichia coli intestinal pathogens are important
      causative agents. Information on the epidemiology of E. coli intestinal pathogens
      and their association with diarrheal disease is limited because no diagnostic
      testing is available in countries with limited resources. To evaluate the
      prevalence of E. coli intestinal pathogens in a Caribbean-Colombian region, E.
      coli clinical isolates from children with diarrhea were analyzed by a recently
      reported two-reaction multiplex polymerase chain reaction (Gomez-Duarte et al.,
      Diagn Microbiol Infect Dis 2009;63:1-9). The phylogenetic group from all E. coli
      isolates was also typed by a single-reaction multiplex polymerase chain reaction.
      We found that among 139 E. coli strains analyzed, 20 (14.4%) corresponded to E.
      coli diarrheagenic pathotypes. Enterotoxigenic, shiga-toxin-producing,
      enteroaggregative, diffuse adherent, and enteropathogenic E. coli pathotypes were
      detected, and most of them belonged to the phylogenetic groups A and B1, known to
      be associated with intestinal pathogens. This is the first report on the
      molecular characterization of E. coli diarrheogenic isolates in Colombia and the
      first report on the potential role of E. coli in childhood diarrhea in this
      geographic area.

PMID- 19839763
TI  - About the comparison of two anabolic agents, teriparatide and strontium ranelate,
      in treated osteoporotic women.

PMID- 19839764
TI  - Vessel formation is induced prior to the appearance of cartilage in BMP-2
      mediated heterotopic ossification.
AB  - Heterotopic ossification (HO), or endochondral bone formation at nonskeletal
      sites, often results from traumatic injury and can lead to devastating
      consequences. Alternatively, the ability to harness this phenomenon would greatly
      enhance current orthopedic tools for treating segmental bone defects. Thus,
      understanding the earliest events in this process potentially would allow us to
      design more targeted therapies to either block or enhance this process. Using a
      murine model of HO induced by delivery of adenovirus-transduced cells expressing
      bone morphogenetic protein 2 (BMP-2), we show here that one of the earliest
      stages in this process is the establishment of new vessels prior to the
      appearance of cartilage. As early as 48 hours after induction of HO, we observed
      the appearance of brown adipocytes expressing vascular endothelial growth factors
      (VEGFs) simultaneous with endothelial progenitor replication. This was determined
      by using a murine model that possesses the VEGF receptor 2 (Flk1) promoter
      containing an endothelial cell enhancer driving the expression of nuclear
      localized yellow fluorescent protein (YFP). Expression of this marker has been
      shown previously to correlate with the establishment of new vasculature, and the
      nuclear localization of YFP expression allowed us to quantify changes in
      endothelial cell numbers. We found a significant increase in Flk1-H2B::YFP cells
      in BMP-2-treated animals compared with controls. The increase in endothelial
      progenitors occurred 3 days prior to the appearance of early cartilage. The data
      collectively suggest that vascular remodeling and growth may be essential to
      modify the microenvironment and enable engraftment of the necessary progenitors
      to form endochondral bone.

PMID- 19839765
TI  - The pivotal role of the alternative NF-kappaB pathway in maintenance of basal
      bone homeostasis and osteoclastogenesis.
AB  - The alternative NF-kappaB pathway consists predominantly of NF-kappaB-inducing
      kinase (NIK), IkappaB kinase alpha (IKKalpha), p100/p52, and RelB. The hallmark
      of the alternative NF-kappaB signaling is the processing of p100 into p52 through
      NIK, thus allowing the binding of p52 and RelB. The physiologic relevance of
      alternative NF-kappaB activation in bone biology, however, is not well
      understood. To elucidate the role of the alternative pathway in bone homeostasis,
      we first analyzed alymphoplasic (aly/aly) mice, which have a defective NIK and
      are unable to process p100, resulting in the absence of p52. We observed
      increased bone mineral density (BMD) and bone volume, indicating an osteopetrotic
      phenotype. These mice also have a significant defect in RANKL-induced
      osteoclastogenesis in vitro and in vivo. NF-kappaB DNA-binding assays revealed
      reduced activity of RelA, RelB, and p50 and no binding activity of p52 in aly/aly
      osteoclast nuclear extracts after RANKL stimulation. To determine the role of
      p100 itself without the influence of a concomitant lack of p52, we used p100(-/-)
      mice, which specifically lack the p100 inhibitor but still express p52. p100(-/-)
      mice have an osteopenic phenotype owing to the increased osteoclast and decreased
      osteoblast numbers that was rescued by the deletion of one allele of the relB
      gene. Deletion of both allele of relB resulted in a significantly increased bone
      mass owing to decreased osteoclast activity and increased osteoblast numbers
      compared with wild-type (WT) controls, revealing a hitherto unknown role for RelB
      in bone formation. Our data suggest a pivotal role of the alternative NF-kappaB
      pathway, especially of the inhibitory role of p100, in both basal and stimulated
      osteoclastogenesis and the importance of RelB in both bone formation and
      resorption.

PMID- 19839766
TI  - Postmenopausal women with osteopenia have higher cortical porosity and thinner
      cortices at the distal radius and tibia than women with normal aBMD: an in vivo
      HR-pQCT study.
AB  - Increases in cortical porosity (Ct.Po) and decreases in cortical thickness
      (Ct.Th) are associated with increased bone fragility. The purpose of this study
      was to validate an autosegmentation method for high-resolution peripheral
      quantitative computed tomography (HR-pQCT) scans to measure Ct.Po and Ct.Th and
      use it to compare Ct.Po and Ct.Th between pre- and postmenopausal women with
      normal, osteopenic, and osteoporotic areal bone mineral density (aBMD). The Ct.Po
      and Ct.Th measurements were validated using cadaver forearms (n = 10) and micro
      computed tomography (microCT) as the gold standard. The analysis was applied to
      distal radius and tibia HR-pQCT scans from a subset of participants from the
      Calgary, Alberta, cohort of the Canadian Multicentre Osteoporosis Study (n = 280,
      18 to 90 years). Analysis of covariance compared Ct.Po and Ct.Th outcomes between
      63 normal premenopausal (dual-energy X-ray absorptiometry femoral neck T-score > 
      1), 87 normal postmenopausal, 121 osteopenic postmenopausal, and 9 osteoporotic
      postmenopausal women. Linear regression analysis and Bland-Altman plots were used
      to assess the agreement between the HR-pQCT and microCT measurements, resulting
      in r(2) values of 0.80 for Ct.Po and 0.98 for Ct.Th. At both sites, Ct.Po was
      higher in postmenopausal (all groups) than in premenopausal women (3.2% to 12.9%,
      p < .001). Ct.Th was not significantly different between normal premenopausal and
      postmenopausal women at either site; however, both osteopenic and osteoporotic
      women had thinner (-12.8% to -30.3%, p < .01), more porous (2.1% to 8.1%, p <
      .001) cortices than normal postmenopausal women. Our method offers promise as a
      valuable tool to measure Ct.Po and Ct.Th in vivo and investigate associations
      among cortical bone structure, age, and disease status.

PMID- 19839767
TI  - On lumpers and splitters: the FRAX debate continues.

PMID- 19839769
TI  - Myeloma bone disease.

PMID- 19839770
TI  - Acute phosphate restriction leads to impaired fracture healing and resistance to
      BMP-2.
AB  - Hypophosphatemia leads to rickets and osteomalacia, the latter of which results
      in decreased biomechanical integrity of bones, accompanied by poor fracture
      healing. Impaired phosphate-dependent apoptosis of hypertrophic chondrocytes is
      the molecular basis for rickets. However, the underlying pathophysiology of
      impaired fracture healing has not been characterized previously. To address the
      role of phosphate in fracture repair, mice were placed on a phosphate-restricted
      diet 2 days prior to or 3 days after induction of a mid-diaphyseal femoral
      fracture to assess the effects of phosphate deficiency on the initial recruitment
      of mesenchymal stem cells and their subsequent differentiation. Histologic and
      micro-computed tomographic (microCT) analyses demonstrated that both phosphate
      restriction models dramatically impaired fracture healing primarily owing to a
      defect in differentiation along the chondrogenic lineage. Based on Sox9 and Sox5
      mRNA levels, neither the initial recruitment of cells to the callus nor their
      lineage commitment was effected by hypophosphatemia. However, differentiation of
      these cells was impaired in association with impaired bone morphogenetic protein
      (BMP) signaling. In vivo ectopic bone-formation assays and in vitro
      investigations in ST2 stromal cells confirmed that phosphate restriction leads to
      BMP-2 resistance. Marrow ablation studies demonstrate that hypophosphatemia has
      different effects on injury-induced intramembranous bone formation compared with
      endochondral bone formation. Thus phosphate plays an important role in the
      skeleton that extends beyond mineralized matrix formation and growth plate
      maturation and is critical for endochondral bone repair.

PMID- 19839771
TI  - Hip fracture causes excess mortality owing to cardiovascular and infectious
      disease in institutionalized older people: a prospective 5-year study.
AB  - An increasing risk of death after hip fracture has been well documented, but the
      duration and causes remain unclear, especially in very frail older people. This
      is a nested case-control study of 229 hip fracture cases and 229 controls matched
      by age, gender, institution type, and follow-up period from a cohort of 2005
      institutionalized older people. The residents were assessed at baseline and
      followed up for hip fracture and death for at least 5 years. Time to death was
      measured from the same time for each case (time of the hip fracture) and the
      matched control. The study sample consisted of 90 males and 368 females with a
      mean age of 86 years (range 67 to 102 years). The hazard ratio (HR) of death for
      the cases compared with the controls was 3.09 [95% confidence interval (CI) 1.83
      5.22, p < .001] for the first 3 months, 1.99 (95% CI 1.13-3.51, p = .02) for the
      period of 3 to 9 months, and 0.88 (95% CI 0.64-1.22, p = .46) for the period
      beyond 9 months following a fracture, after adjusting for age, gender,
      institution type, weight, immobility, cognitive function, comorbidities, and
      number of medications. The main causes of the excess mortality in the first 9
      months were infections (HR = 6.66, 95% CI 1.95-22.77, p = .002) for females and
      cardiac disease (HR = 2.68, 95% CI 1.39-5.15, p = .003) for both males and
      females. Bisphosphonate use was associated with a reduction in mortality after
      hip fracture (p = .002). Intensive medical supervision to reduce cardiovascular
      and infective complications should be provided for frail older people with recent
      hip fracture to reduce mortality.

PMID- 19839772
TI  - Antiepileptic drug use, falls, fractures, and BMD in postmenopausal women:
      findings from the women's health initiative (WHI).
AB  - Antiepileptic drugs (AEDs) are used increasingly in clinical practice to treat a
      number of conditions. However, the relationship between the use of these
      medications, particularly the newer AEDs, and fracture risk has not been well
      characterized. We used data from the Women's Health Initiative (WHI) to determine
      the relationship bewteen the use of AEDs and falls, fractures, and bone mineral
      density (BMD) over an average of 7.7 years of follow-up. We included 138,667
      women (1,385 users of AEDs and 137,282 nonusers) aged 50 to 79 years in this
      longitudinal cohort analyses. After adjustment for covariates, use of AEDs was
      positively associated with total fractures [hazard ratio (HR) = 1.44, 95%
      confidence interval (CI) 1.30-1.61], all site-specific fractures including the
      hip (HR = 1.51, 95% CI 1.05-2.17), clinical vertebral fractures (HR = 1.60, 95%
      CI 1.20-2.12), lower arm or wrist fractures (HR = 1.40, 95% CI 1.11-1.76), and
      other clinical fractures (HR = 1.46, 95% CI 1.29-1.65) and two or more falls (HR
      = 1.62, 95% CI 1.50-1.74) but not with baseline BMD or changes in BMD (p > or =
      .064 for all sites). Use of more than one and use of enzyme-inducing AEDs were
      significantly associated with total fractures (HR = 1.55, 95% CI 1.15-2.09 and HR
      = 1.36, 95% CI 1.09-1.69, respectively). We conclude that in clinical practice,
      postmenopausal women who use AEDs should be considered at increased risk for
      fracture, and attention to fall prevention may be particularly important in these
      women.

PMID- 19839774
TI  - Persistent secondary hyperparathyroidism and vertebral fractures in kidney
      transplantation: role of calcium-sensing receptor polymorphisms and vitamin D
      deficiency.
AB  - Bone morbidity remains a major problem even after successful renal
      transplantation. We investigated the role of calcium-sensing receptor (CaSR)
      polymorphisms and 25-hydroxyvitamin D levels on the persistence of secondary
      hyperparathyroidism (SHPT) and their relationships with vertebral fractures (VFx)
      in 125 renal allograft recipients transplanted 44 +/- 23 months before. All
      patients underwent evaluation of the main biochemical parameters of calcium
      metabolism as well as vertebral and femoral bone density. In 87 patients, CaSR
      polymorphisms (A986S, R990G, and Q1011E) also were assessed. X-ray images of the
      lateral spine were obtained in 102 subjects to perform vertebral morphometry.
      High parathyroid hormone (PTH) and 25-hydroxyvitamin D lower than 80 nmol/L were
      found in 54% and 97% of patients, respectively, with 40% of these showing vitamin
      D levels lower than 30 nmol/L. VFx were detected in 57% of the subjects. After
      multiple adjustments, 25-hydroxyvitamin D, age, and hemodialysis duration, but
      not CaSR polymorphisms, were found to be significant predictors of high PTH,
      whereas age and time since transplant were positively related with lower 25
      hydroxyvitamin D values. PTH and time since transplant were significantly
      associated with VFx. Patients with two or more VFx showed serum PTH levels 50%
      higher than patients without fractures. We therefore conclude that persistent
      SHPT is a very common feature after renal transplantation and that, unlike CaSR
      polymorphisms, low 25-hydroxyvitamin D is involved in its pathogenesis. High PTH
      levels, in turn, are associated with an increased VFx risk, which confirms the
      need for strategies aimed at lowering serum PTH in this setting as well.

PMID- 19839775
TI  - Evolving role of imaging in the evaluation of bone structure.

PMID- 19839777
TI  - Rare mutations in the PIK3CA gene contribute to aggressive endometrial cancer.
AB  - The molecular basis of endometrial cancer (EC), a common gynecologic malignancy,
      often includes mutational activation of the PIK3CA and KRAS genes. We aimed to
      determine the distribution of mutations in the two genes depending on patient
      clinocopathological characteristics. We sequenced exon 1 of the KRAS gene and
      exons 9 and 20 of the PIK3CA gene in 108 consecutive EC tumor samples. PIK3CA
      mutations were present in 24 of the 108 (22.2%) cases and KRAS mutations in 18 of
      the 108 (16.7%) cases. PIK3CA mutations occurred more frequently in KRAS-mutated
      samples (7/18, 38.9%; p = 0.06) than in KRAS wild type (17/90, 18.9%) and showed
      a very high frequency in metastatic tumors (4/9, 44.4%; p = 0.1) and in samples
      displaying serous differentiation-serous and mixed endometrioid/serous tumors
      (6/12, 50.0%; p = 0.021)-where KRAS mutations were rare (11.1% and 16.7%,
      respectively) and did not exist independently of a PIK3CA mutation. Non-hotspot
      (i.e., non-E542K, -E545K, and -H1047R) mutations in the PIK3CA gene showed higher
      frequency in metastatic cases (3/9, 33.3%; p = 0.05). Tumors displaying serous
      differentiation showed a particular pattern-they harbored exclusively mutations
      in PIK3CA exon 20 (5/12, 41.7%; p = 0.005) and most of these were non-hotspot
      (4/12, 33.3%; p = 0.02). In all other comparisons exons 9 and 20 mutation
      distribution did not differ. These results suggest the need for further
      exploration of the significance of PIK3CA mutations in respect to aggressive EC.

PMID- 19839778
TI  - Association between bone morphogenetic protein 4 gene polymorphisms with
      nonsyndromic cleft lip with or without cleft palate in a chilean population.
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most
      common birth defects in humans with both genetic and environmental components
      involved in its expression. Experimental evidences have postulated that bone
      morphogenetic protein 4 gene (Bmp4) is involved in the etiology of cleft lip with
      or without cleft palate (CL/P) in mice. In our study we analyzed the association
      between BMP4 and NSCLP in a sample of 150 unrelated trios ascertained through
      affected probands. Three BMP4 polymorphisms were analyzed, two intronic (rs762642
      and rs2855532) and rs1957860, located 5.7 kb upstream from BMP4.
      Transmission/disequilibrium tests were performed at the allele and haplotype
      levels. Our results did not detect preferential transmission for individual
      single-nucleotide polymorphisms. Significant transmission distortion was observed
      for haplotypes rs1957860-rs762642 (p = 0.018), especially for C-T (p = 0.015) and
      T-T (p = 0.018) which include the genomic region where the promoter and an
      enhancer of BMP4 are located. Thus, despite the positive association detected
      between these haplotypes and NSCLP they probably do not have a functional effect
      on BMP4 expression or protein activity but possibly reflect NSCLP susceptibility
      changes which are in linkage disequilibrium with these polymorphisms. The
      findings of our study support a role for BMP4 in NSCLP in the admixed Chilean
      population.

PMID- 19839776
TI  - Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene
      expression in bone marrow stromal cells.
AB  - We previously reported that specific oxysterols stimulate osteogenic
      differentiation of pluripotent bone marrow stromal cells (MSCs) through
      activation of hedgehog (Hh) signaling and may serve as potential future therapies
      for intervention in osteopenia and osteoporosis. In this study we report that the
      osteogenic oxysterol 20(S)-hydroxycholesterol (20S) induces the expression of
      genes associated with Notch signaling. Using M2-10B4 (M2) MSCs, we found that 20S
      significantly induced HES-1, HEY-1, and HEY-2 mRNA expression compared with
      untreated cells, with maximal induction after 48 hours, whereas the nonosteogenic
      oxysterols did not. Similar observations were made when M2 cells were treated
      with sonic hedgehog (Shh), and the specific Hh pathway inhibitor cyclopamine
      blocked 20S-induced Notch target gene expression. 20S did not induce Notch target
      genes in Smo(-/-) mouse embryonic fibroblasts, further confirming the role of Hh
      signaling in 20S-induced expression of Notch target genes. Despite the inability
      of liver X-receptor (LXR) synthetic ligand TO901317 to induce Notch target genes
      in M2 cells, LXR knockdown studies using siRNA showed inhibition of 20S-induced
      HEY-1 but not HES-1 expression, suggesting the partial role of LXR signaling in
      MSC responses to 20S. Moreover, 20S-induced Notch target gene expression was
      independent of canonical Notch signaling because neither 20S nor Shh induced CBF1
      luciferase reporter activity or NICD protein accumulation in the nucleus, which
      are hallmarks of canonical Notch signaling activation. Finally, HES-1 and HEY-1
      siRNA transfection significantly inhibited 20S-induced osteogenic genes,
      suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1
      and HEY-1.

PMID- 19839779
TI  - Single-incision transureteral laparoscopic nephrectomy: a proof of concept.
AB  - PURPOSE: Single-umbilical incision laparoscopic nephrectomy has been recently
      advocated as an alternative to pure natural orifice transluminal endoscopic
      surgery. We present a novel, hybrid technique for laparoscopic nephrectomy that
      combines single-incision laparoscopy with natural orifice transluminal endoscopic
      surgery principles consisting of using the ureteral stump as a natural orifice.
      MATERIALS AND METHODS: Six renal units were operated in a nonsurvival pig study
      by combining a single umbilical incision with a novel natural orifice, the
      divided ureter. A transurethral 16F Amplatz sleeve inserted in the ureter under
      cystoscopic guidance became a natural orifice port after transection of the
      ureter. Regular laparoscopic instruments and scopes were used through two
      adjacent single-incision umbilical ports. The camera was placed in one of the
      umbilical ports and two operating instruments were introduced through the
      additional umbilical port and the "natural orifice port," respectively. RESULTS:
      Right and left laparoscopic nephrectomy were successfully performed. No
      complications occurred except one case of a periureteral hematoma due to the
      dilation of the ureter. The hylar blood vessels were thoroughly dissected and
      controlled by either clips or vascular staplers. The operative time decreased
      from 140 minutes in the first procedure to 70 minutes in the last (median time:
      85 minutes). The learning curve was short because the basic principles of
      laparoscopy such as correct instrument angulation and geometry could be achieved
      through the inferior, natural orifice port. CONCLUSIONS: Laparoscopic nephrectomy
      combining a single umbilical incision with a natural orifice provided by the
      ipsilateral ureter is technically feasible in a large animal model. Further
      studies in human patients together with assessment of advantages over classic
      laparoscopic nephrectomy are needed.

PMID- 19839780
TI  - Renal functional outcomes after cryoablation of small renal masses.
AB  - BACKGROUND AND PURPOSE: Renal function outcomes after renal cryosurgery have not
      been widely scrutinized. We report 2-year renal function outcomes from a single
      center cohort of patients who were treated with cryoablation for small renal
      masses. METHODS: We performed a retrospective review of our laparoscopic and
      percutaneous renal cryoablation experience between January 2003 and April 2007.
      Global renal function was assessed using measured serum creatinine and estimated
      glomerular filtration rate (eGFR) (MDRD equation). Chronic kidney disease (CKD)
      was defined as a serum creatinine level >2.0 mg/dL or eGFR <60 mL/min/1.73 m(2).
      RESULTS: Sixty-two patients were included in the analysis. Mean follow-up was 30
      months (range 13-63 mos). Mean tumor size was 2.33 cm (range 1-4.6 cm). Comorbid
      conditions were prevalent: 77% hypertension, 35% hyperlipidemia, 31% diabetes
      mellitus, 39% tobacco use, and 32% heart disease (coronary artery
      disease/congestive heart failure). Based on eGFR calculations, preoperative CKD
      was noted in 17 of 62 (27%) patients. De novo CKD was noted in 5 of 45 (11%)
      patients. Patients in whom de novo CKD developed had lower pretreatment eGFR
      (71.0 vs 98.4 60 mL/min/1.73 m(2), P = 0.03) and larger tumor size (2.94 vs 2.19
      cm, P = 0.04) compared with patients who were maintaining normal renal function.
      When CKD was defined as creatinine level >2.0 mg/dL, only one and six patients
      were identified with preoperative and de novo CKD, respectively. CONCLUSIONS: In
      a cohort of renal cryosurgery patients who were characterized by highly prevalent
      medical comorbidities, renal function was generally well maintained, with a low
      rate of de novo CKD based on eGFR calculations. A serum creatinine level >2.0
      mg/dL was a less sensitive measure of CKD.

PMID- 19839781
TI  - The effect of age on acquiring laparoscopic skills.
AB  - BACKGROUND AND PURPOSE: Laparoscopic surgery is well known as having a long and
      variable learning curve. In fact, successive generations of surgeons were able to
      reduce their operative time and plateau their learning curves. This raises the
      question as to how early in medical education we can integrate laparoscopic
      skills. In this study, we are trying to demonstrate the effect of age on
      acquiring new laparoscopic skills. METHODS: Thirty-two trainees at various
      educational levels and ages were recruited to our study. Trainees were divided
      into four age groups with eight persons in each group. Senior high school
      students, undergraduate college students, medical students, and junior surgery
      residents comprised the first, second, third, and the fourth groups,
      respectively. The trainees performed nine inanimate laparoscopic tasks in the
      laparoscopic training box and repeated each task five times. The time needed for
      each trial was recorded, and the results were statistically analyzed. RESULTS:
      The youngest group of trainees showed the largest improvement in performance
      time, followed by the second and third groups. The most senior group showed the
      least improvement. CONCLUSION: These preliminary data suggest that younger
      trainees are faster to acquire new laparoscopic skills than the older persons.
      This finding suggests a potential benefit from earlier integration of
      laparoscopic skills in medical education.

PMID- 19839782
TI  - Laparoscopic retroperitoneal lymph node dissection for high-risk pediatric
      patients with paratesticular rhabdomyosarcoma.
AB  - BACKGROUND AND PURPOSE: Retroperitoneal lymph node dissection (RPLND) is
      recommended in children 10 years or older with paratesticular rhabdomyosarcoma
      (PTRMS). Primary tumors >5 cm are an additional risk factor for disease
      recurrence in the retroperitoneum. We report our experience with laparoscopic
      RPLND (LRPLND) in high-risk pediatric patients with PTRMS. PATIENTS AND METHODS:
      Three patients, mean age 13.6 years (range 10-16 yrs), underwent modified
      template LRPLND after radical orchiectomy for preoperative rhabdomyosarcoma stage
      T(1a)N(0)M(0), T(1b)N(0)M(0), and T(2b)N(0)M(0), respectively. Primary
      paratesticular masses measured a mean 7.5 cm (range 4-10 cm). LRPLND was
      performed a mean of 8.6 days (range 7-12 d) after radical orchiectomy using four
      trocars that were placed equidistant in the midline. RESULTS: Average operative
      time was 382 minutes (range 245-656 minutes). Mean estimated blood loss was 53 mL
      (range 10-75 mL), and mean postoperative hospital stay was 2.5 days (range 2-3
      d). There were no postoperative complications. Retroperitoneal nodes had negative
      findings for microscopic disease in two patients and positive findings in one
      patient. All patients received adjuvant chemotherapy with vincristine,
      actinomycin, and cyclophosphamide. CONCLUSION: LRPLND for high-risk pediatric
      patients with PTRMS is a safe diagnostic and therapeutic procedure with the
      benefit of rapid convalescence, enabling early commencement of adjuvant
      chemotherapy.

PMID- 19839783
TI  - Video technique for human robot-assisted microsurgical vasovasostomy.
AB  - Previous studies have shown that robot-assisted microsurgical vasovasostomy
      (RAVV) has technical advantages over pure microscopic vasovasostomy (MVV) in
      animal and human models. This study presents a video technique and initial
      results for RAVV in 20 human cases compared with 7 MVV cases by a single
      fellowship-trained microsurgeon from July 2007 to June 2009. A three-layer 10-0
      and 9-0 suture anastomosis was performed with up to 22 months follow-up (mean 3
      months). Mean operative duration for the RAVV cases was 109 and 128 minutes for
      MVV (p = 0.09). At 2 months postoperatively, all patients were patent. Mean sperm
      count was 54 million in RAVV and 11 million in MVV (p = 0.04). The use of robotic
      assistance in microsurgical vasovasostomy may have potential benefit over MVV in
      decreasing operative duration and significantly improving early semen analysis
      measures. Further evaluation and longer follow-up is needed to assess its
      clinical potential.

PMID- 19839784
TI  - Symptoms related to ureteral stents in renal transplants compared with stents
      placed for other indications.
AB  - OBJECTIVE: To use a validated questionnaire to compare indwelling ureteral stent
      symptoms in patients who had the ureteral stent placed during renal
      transplantation with patients who had retrograde insertion of the stent in a
      native kidney during endoscopic procedures. METHODS: Symptoms related to the
      presence of a ureteral stent were assessed prospectively in the two patient
      groups. Just before stent removal, patients completed a validated Ureteral Stent
      Symptom Questionnaire evaluating urinary symptoms, body pain, general health,
      work performance, and sexual function. Categorical scores and individual factors
      were qualitatively and statistically compared between the two groups. RESULTS:
      Twenty-eight (15 men and 13 women) patients (mean age 56, range 72-32) underwent
      renal transplantation with ureteral stents removed after a mean of 41 days (range
      9-81). Seventeen (4 men and 13 women) patients (mean age 43, range 73-17) had
      ureteral stents placed in native kidneys for other indications with subsequent
      removal after a mean of 24 days (range 6-61). The transplant group had
      statistically fewer urinary symptoms (p = 0.001), pain symptoms (p < 0.001),
      better overall health index (p = 0.005), and improved quality of work (p =
      0.008). Transplant patients complained of fewer urinary symptoms (urgency,
      dysuria, dribbling, and hematuria), required less additional antibiotic use, and
      had fewer additional clinic or hospital visits. CONCLUSIONS: Ureteral stents
      inserted during renal transplantation result in significantly fewer symptoms when
      compared with stents inserted in the native ureter. This, in part, may be because
      of less trigonal irritation by the stent when the ureteral implantation is in the
      dome of the bladder.

PMID- 19839785
TI  - Eudragit S100 microparticles containing Spodoptera frugiperda
      nucleopolyehedrovirus: physicochemical characterization, photostability and in
      vitro virus release.
AB  - The aim of this study was to encapsulate the occlusion bodies (OBs) of Spodoptera
      frugiperda nucleopolyhedrovirus (SfNPV) in Eudragit S100 microparticles (MPs),
      considering this technique as a possible alternative to protect them from
      deleterious environmental conditions. The MPs were prepared by oil-in-oil
      emulsion (O/O) solvent evaporation method. Experimental conditions were
      established according to a previous multi-level experimental design involving the
      core/polymer ratio as independent variable. The effects of these parameters on
      particle size and process yield were investigated observing that polymer
      concentration had a significant effect on particle size. After adequate
      conditions for MPs formation were determined, virus was encapsulated. The virus
      microparticles presented a particle size between 50-300 microm and concentration
      was 2.62 x 10(9) OBs g(-1). Microencapsulation efficiency was 53.43% and virus
      release adjusted to Higuchi model suggesting diffusion as the release mechanism.
      Evaluated microencapsulation process protected viral particles of UV
      inactivation, suggesting its potential for a biopesticide development.

PMID- 19839786
TI  - Pharmacokinetics and tissue distribution of liposomal etoposide in rats.
AB  - Precipitation of etoposide and adverse events associated with the co-solvents in
      intravenous solutions can be avoided by using liposomal etoposide (LE). The
      pharmacokinetics and distribution of the commercial formulation (ETPI) and LE
      were compared in rats. The pharmacokinetic profiles were biphasic and similar in
      the initial phase (C(max), Vd, and t(1/2alpha)). However, LE showed a 60%
      increase in AUC with a 35% decrease in clearance (p < 0.05). This decreased
      clearance resulted in a 70% increase in the MRT of etoposide. The uptake of
      etoposide from LE was higher in macrophage-phagocytic endowed tissues indicating
      that LE is superior to ETPI for targeted delivery of etoposide.

PMID- 19839787
TI  - Influence of polymers ratio on insulin-loaded nanoparticles based on poly-epsilon
      caprolactone and Eudragit RS for oral administration.
AB  - Nanoparticles loaded with two different commercial insulins (Actrapid, Novorapid
      and based on different blends of a biodegradable polyester (poly-epsilon
      caprolactone) and a polycationic non-biodegradable acrylic polymer (Eudragit RS)
      were characterized in vitro. The zeta potential was positive whenever Eudragit RS
      was part of the nanoparticles matrix. The encapsulation efficiency was ~ 96%
      except for Novorapid-loaded particles of poly-epsilon-caprolactone (only 35%). In
      vitro release studies revealed a burst release from nanoparticles, which may be
      of interest for oral delivery. Novorapid-loaded nanoparticles were orally
      administered to diabetic rats and allowed the glycemia to be decreased when
      compared with free nanoparticles.

PMID- 19839788
TI  - Targeted delivery of an anti-cancer agent via steroid coupled liposomes.
AB  - In the present investigation, testosterone (T) was evaluated as a targeting
      ligand to direct the site-specific delivery of 5-Fluorouracil (5-FU) bearing
      liposomes to the androgen receptor (ARs) positive tumors and other organs like
      prostate, brain, and testis. The testosterone was conjugated with the distearoyl
      phosphatidyl ethanolamine (DSPE) and then this lipid conjugate, Testosterone-DSPE
      (T-DSPE) was used as one of the components of the liposome. The liposomes were
      prepared by cast film method using T-DSPE, egg PC, and cholesterol. Further these
      liposomes were characterized for vesicle shape, average size, polydispersity
      index, drug entrapment, and in vitro drug release. It was observed that the
      prepared liposomes were spherical in shape with an average size of 232 +/- 21 nm
      and 0.181 +/- 0.064 polydispersity index. The in vitro drug release study showed
      79.50 +/- 2.81 percent drug release in 24 h. In vivo performance of the developed
      liposomes was evaluated using organ distribution study in male albino rats.
      Moreover the fluorescent microscopy was also performed using 6-Carboxyfluorescein
      (6-CF) as a fluorescent marker. The organ distribution and fluorescent uptake
      studies confirm that T-DSPE coupled liposomes were effectively taken up by
      various ARs expressing tissues. Thus, it may be concluded that the testosterone
      may be used as an effective ligand for the site-specific delivery of anti-cancer
      agents to various ARs positive carcinomas.

PMID- 19839789
TI  - Formulation and in vitro evaluation of a PEGylated microscopic lipospheres
      delivery system for ceftriaxone sodium.
AB  - The aim of this study was to formulate and evaluate in vitro, ceftriaxone sodium
      lipospheres dispersions for oral administration. Ceftriaxone sodium lipospheres
      were prepared by melt-emulsification using 30%w/w Phospholipon 90H in Softisan
      154 as the lipid matrix containing increasing quantities of PEG 4000 (10, 20, 30,
      and 40%w/w). Characterization based on particle size, particle morphology,
      encapsulation efficiency, loading capacity and pH were carried out on the
      lipospheres. Microbiological studies of the ceftriaxone sodium-loaded lipospheres
      were performed using Escherichia coli as the model organism. In vitro permeation
      of ceftriaxone sodium from the lipospheres through artificial membrane (0.22
      microm pore size) was carried out using Franz cell and simulated intestinal fluid
      (SIF) without pancreatin as acceptor medium. Photomicrographs revealed spherical
      particles within a micrometer range with minimal growth after 1 month (Maximum
      size = 64.76 +/- 3.81 microm). Microbiological studies indicated that lipospheres
      formulated with 20%w/w of PEG 4000 containing 2%w/w or 3%w/w of ceftriaxone
      sodium gave significantly (p < 0.05) higher inhibition zone diameter than those
      with 30%w/w or 40%w/w of PEG 4000. The result also indicated that lipospheres
      with 10%w/w PEG 4000 resulted in significantly higher encapsulation efficiency (p
      < 0.05) while those with 30%w/w gave the least, while the loading capacity values
      ranged from 3.22 mg of ceftriaxone sodium/100 mg of lipid to 6.36 mg of
      ceftriaxone sodium/100 mg of lipid. Permeation coefficient values varied and
      ranged from 8.55 x 10(-7) cm/s to 2.08 x 10(-6) cm/s depending on the
      concentration of PEG 4000. The result of this study gave insight that the issue
      of ceftriaxone stability in oral formulation could be adequately addressed by
      tactical engineering of lipid drug delivery systems such as lipospheres.

PMID- 19839790
TI  - Preparation of N,O-carboxymethyl chitosan nanoparticles as an insulin carrier.
AB  - The aim of this research was to develop pH-sensitive insulin-loaded NOCC (N,O
      carboxymethyl chitosan) nanoparticles for the controlled release of insulin via
      the oral route. Thus, in this study, insulin-loaded NOCC nanoparticles were
      prepared by ionic gelation of NOCC with TPP (tripolyphosphate). NOCC
      nanoparticles were formed at conditions of 2 mg/ml of NOCC and 1 mg/ml of TPP. It
      was found that the encapsulation efficiency and process yield decreased with
      increasing NOCC to TPP weight ratio. Furthermore, the cumulative release of
      insulin from insulin-loaded NOCC nanoparticles decreased with decreasing NOCC-to
      TPP weight ratio, but it increased with decreasing the initial concentration of
      insulin. The higher the pH of the phosphate buffered saline, the greater the
      amount of cumulative release of insulin-loaded NOCC nanoparticles, and thus they
      could protect insulin from acid.

PMID- 19839791
TI  - Biodegradable alginate microparticles developed by electrohydrodynamic spraying
      techniques for oral delivery of protein.
AB  - In this study, alginate microparticles were prepared by cross-linking alginate
      with calcium chloride solution using an electrohydrodynamic spraying technique.
      The effects of alginate and calcium chloride concentration as well as electrical
      potential on particle size and shape were investigated. The results showed that 1
      mg ml(-1) alginate medium viscosity (AMV), 2.5 mg ml(-1) CaCl(2), electrical
      potential 18 kV (F1) and 0.5 mg ml(-1) alginate low viscosity (ALV), 2.5 mg ml(
      1) CaCl(2), electrical potential 20 kV (F2) yielded the spherical shape and small
      particles of 937 +/- 158 nm and 1556 +/- 51 nm, respectively. In bovine serum
      albumin (BSA) entrapment efficiency study, initial BSA of 5, 10, 20, 40 and 60%
      w/w to polymer was incorporated into these alginate microparticles. The results
      revealed that F2 with initial BSA 10% w/w showed the highest entrapment
      efficiency of 49.70 +/- 0.01%. The result of BSA content revealed that F2' with
      the initial BSA of 20% w/w showed the highest amount of BSA content of 3.92 +/-
      0.02 mg g(-1) of particles. F1 and F2 with the initial BSA of 5%, 20% and 40% w/w
      were chosen to evaluate for the release in PBS pH 7.4. It was found that F1 with
      the initial BSA of 40% w/w showed the slowest release rate and sustained release.
      The release of F1 in 0.1 N HCl solution (pH 1.2) was slower than that in pH 7.4.
      This electrohydrodynamic spray technique (EHDA) can be applied to prepare
      alginate in micro size and can encapsulate BSA. Alginate microparticles can
      further be optimized for oral delivery of several pharmaceutical peptides and
      proteins.

PMID- 19839792
TI  - Protein-loaded microspheres prepared by sequential adsorption of dextran sulphate
      and protamine on melamine formaldehyde core.
AB  - Polyelectrolyte multilayer microspheres were fabricated by layer-by-layer self
      assembly of a dextran sulphate and a protamine on melamine formaldehyde cores,
      followed by the partial decomposition of the core. Effects of pH on the
      encapsulation of proteins and enzymes with different physico-chemical properties
      (insulin, aprotinin, peroxidase, glucose oxidase (GOD), catalase (Cat)) in the
      prepared microspheres were then studied. This method of protein encapsulation
      demonstrated a high loading capacity and efficiency. The protein incorporation
      and release was regulated by the pH of the solution. Encapsulated enzymes
      retained a high specific activity depending on the amount of protein
      incorporated. Bienzyme system GOD/Cat immobilized in the microspheres was
      suitable for the glucose content assay.

PMID- 19839793
TI  - Amphotericin B microspheres: a therapeutic approach to minimize toxicity while
      maintaining antifungal efficacy.
AB  - Amphotericin B microsphere formulations with and without addition of polyethylene
      glycol 2000 in cross-linked bovine serum albumin were prepared. Amphotericin B
      microspheres were characterized for particle size (<5 microm), zeta potential
      (approximately 30 mV) and drug interaction by DSC and FTIR and were found to be
      stable formulations. Drug release profiles for these microspheres revealed that
      the release was primarily by diffusion. In vitro toxicity as assessed by release
      of haemoglobin and potassium demonstrated no toxic effect as compared with
      conventional solution formulation. Antifungal activity in vitro was comparable to
      solution formulation when tested by broth dilution method.

PMID- 19839794
TI  - Preliminary in vivo studies of a new lecithin-based formulation of paclitaxel.
AB  - Amorphous paclitaxel dissolves rapidly (1 mg mL(-1)) in an isotonic aqueous
      dispersion of egg lecithin (5% w/w), a new biocompatible submicron drug carrier
      consisting of structured aggregates with average size 0.5 microm. The solution is
      physically stable for at least 24 h and can be administered as an intravenous
      infusion. After a 5 h infusion in rabbits (0.66 mg kg(-1) h(-1)), changes in
      blood morphology were comparable to those observed in rabbits that received the
      commercial product Taxol. No changes in the enzyme profiles (alanine/aspartate
      aminotransferase or alkaline phosphatase) were observed. However, during infusion
      of the new formulation plasma concentration of paclitaxel (292 +/- 182 ng mL(-1))
      was lower than observed after Cremophor-containing Taxol (540 +/- 262 ng mL(-1)).
      This result may indicate that the tissue distribution is different for the two
      drug formulations. Daily intraperitoneal administrations (3 doses/day) in mice
      demonstrated that the new carrier solution was non-toxic and, relative to Taxol,
      the new formulation exhibited similar or less toxicity.

PMID- 19839795
TI  - Preparation and characteristics of chitosan microspheres in different acetylation
      as drug carrier system.
AB  - Chitosan microspheres (CM) and reacetylated chitosan microspheres (ACM) were
      successfully made by the methods of oil/water emulsification and acetic
      anhydride. The characteristics of the microspheres as a drug carrier system were
      investigated. Two microsphere samples had spherical shape with the mean diameter
      of 80.79 microm for CM and 81.25 microm for ACM. The in vitro degradation (pH
      7.4) in the presence of lysozyme showed a slow mass loss and ACM was higher
      degradation compared to CM. The microspheres, especially ACM, had a high drug
      loading capacity of Adriamycin hydrochloride (ADM) (12.4%) and had sustained
      release. The cytotoxicity was evaluated in vitro via MTT assay, ACM with steadily
      continual adhesion to cells had no fibroblast cytotoxicity. The inhibitory rates
      of ADM-loading CM, ACM suspension to Tca 8113 cells were significantly
      outperformed that of ADM solution.

PMID- 19839796
TI  - Encapsulation of complex extracts in beta-cyclodextrin: an application to
      propolis ethanolic extract.
AB  - Propolis ethanolic extracts (PE) are rather complicated mixtures of bioactive
      compounds belonging to several chemical classes. The potential use of beta
      cyclodextrin (beta-CD) cavity for the incorporation of specific PE components,
      aiming to increase their solubility in water, was studied in a Greek propolis,
      which was rich in polyphenols and terpenes. The PE/beta-CD inclusion complexes
      were prepared by sonication of PE suspensions in aqueous solutions of beta-CD,
      followed by filtration and freeze-drying. The aqueous solubility of PE in the
      presence of beta-CD was studied by the construction of solubility diagrams and by
      determining the fraction of PE constituents that was dissolved in water.
      Encapsulation efficiencies were found to be higher (9.4-23.3%) for relatively
      small aromatic molecules like cinnamic and benzoic acid derivatives and lower for
      terpenic acids (5.0-6.7%), anthraquinones (3.6-8.4%) and flavonoids (4.0-10.7%).
      The respective in vitro solubilities in simulated gastric fluid followed an
      opposite trend, being lower for the relatively small aromatic molecules. It is
      concluded that the encapsulation in beta-CD may increase the solubility of PE
      constituents in a manner related to their structure, while the amount of
      substances released will depend both on their chemical properties and on their
      relative abundance in the matrix.

PMID- 19839797
TI  - Effect of lipid types on physicochemical characteristics, stability and
      antioxidant activity of gamma-oryzanol-loaded lipid nanoparticles.
AB  - In the present study gamma-oryzanol, an antioxidant, was incorporated into three
      different types of solid lipid: wax, triglycerides, a mixture of glycerides as
      solid lipid nanoparticles (SLN) and liquid lipid (Miglyol 812) as nanoemulsion
      (NE). Instability was found only from NE due to its significant increase in
      particle size and decreased entrapment efficiency (%EE) at a storage temperature
      of 45 degrees C. Solid lipid type in SLN plays an important role only on %EE, but
      not chemical stability. A decrease in crystallinity of SLN was observed with the
      incorporation of gamma-oryzanol and low recrystallization index were found with
      two glycerides-based SLN. The in vitro release studies demonstrated that a
      biphasic release pattern fitted well with the Higuchi model of SLN formulations.
      In comparison, nearly constant release was observed in NE comprised of similar
      composition. Wax-based SLN demonstrated the lowest cytotoxicity. NE, wax-based
      SLN and a mixture of glycerides-based SLN were considered to enhance the
      antioxidant activity of gamma-oryzanol.

PMID- 19839798
TI  - Pharmacokinetic and biodistribution studies of amphotericin B microspheres.
AB  - The pharmacokinetics of Amphotericin B (AmB) from polyethylene glycol 2000 (PEG
      2000) entrapped cross-linked bovine serum albumin (BSA) microsphere formulations
      were investigated and compared with solution formulation. The microsphere
      preparations were characterized for particle size using electron microscopy, zeta
      potential and encapsulation efficiency. The microsphere formulations demonstrated
      a sustained release of AmB for a longer period of time, with no rise in plasma
      creatinine and potassium levels. The enhanced AmB accumulation in lungs was
      observed which could be of importance since lungs are the primary target in most
      fungal infections. The stealth property of submicron cross-linked BSA
      microspheres in formulations containing PEG 2000 (formulation F-2N) and without
      PEG 2000 (formulation F-1N) was also evaluated. There was no evidence that
      microspheres embedded with PEG remained longer in circulation; however, it was
      noticed that the internalization of formulation F-2N microspheres was delayed
      when compared with microspheres from formulation F-1N.

PMID- 19839799
TI  - Formulation and in vitro evaluation of buoyant controlled release lercanidipine
      lipospheres.
AB  - The aim of this study was to prepare and evaluate buoyant lipospheres containing
      lercanidipine hydrochloride. The lipospheres were prepared by modified melt
      dispersion technique using hydrophobic matrix of cetostearyl alcohol (CSA). The
      influence of formulation factors (stirring speed, lipid:drug ratio,
      lipid:surfactant polymer composition) on particle size, encapsulation efficiency
      and in-vitro release characteristics of lipospheres were investigated. The yields
      of all prepared formulation and encapsulation efficiencies were high for
      formulations which contain high lipid amount. The mean particle size
      significantly decreased (p < 0.001) by increasing the lipid:surfactant polymer
      and stirring speed (p < 0.001) of the system. Reduction in encapsulation
      efficiency (p < 0.001) and drug content (p < 0.001) was observed with increasing
      stirring speed and percentage of poloxamer 407 in formulation. Although
      lercanidipine hydrochloride release from Cetostearyl alcohol lipospheres were
      very slow and incomplete for all formulations f1-f6 ( approximately 65% drug
      released in 12 h) and was increased (approximately 85% drug released in 12 h) in
      lipospheres formulations f7-f12, containing Poloxamer 407. Percentage of buoyant
      lercanidipine lipospheres of CSA (96-100% buoyancy up to 12 h) decreases (p <
      0.001) with increasing percentage of poloxamer 407 and achieved the release
      profile suitable for peroral administration.

PMID- 19839801
TI  - Anti-inflammatory effects of locally applied enzyme-loaded ultradeformable
      vesicles on an acute cutaneous model.
AB  - Superoxide dismutase (SOD) and catalase (CAT) are active scavengers of reactive
      oxygen species and were incorporated into ultradeformable vesicles with the aim
      of increasing enzyme bioavailability (skin delivery). These special very
      adaptable vesicles have been formulated and optimized for enzyme transport in
      order to penetrate into or across the intact skin barrier. Anti-inflammatory
      activity of SOD-loaded, CAT-loaded and of SOD- and CAT-loaded ultradeformable
      vesicles applied epicutaneously was measured using different protein doses on the
      skin, on an arachidonic acid-induced mouse ear oedema. The biological anti-oedema
      activity is a measurement of drug-targeting potentiation in the organ. Delivery
      by means of deformable vesicles was compared to conventional vesicles or the
      absence of an enzyme carrier mediated transport. This was done at various times
      following prophylactic application of the test formulations. Positive reference
      groups were treated epicutaneously with several low molecular weight non
      steroidal anti-inflammatory drugs (NSAIDs). The latter included indomethacin (3
      mg kg(-1)), etofenamate (30 mg kg(-1)) and piroxicam (1 mg kg(-1)) and reduced
      the oedema by 94 +/- 4%, 81 +/- 4% and 42 +/- 5%, respectively, if measured 30
      min after ear treatment with a NSAID. Of the enzyme-loaded carriers tested, only
      the enzyme-loaded ultradeformable vesicles reduced the swelling of ears
      significantly: SOD (90 microg kg(-1)), CAT (250 microg kg(-1)) and SOD (90 microg
      kg(-1)) plus CAT (250 microg kg(-1)) reduced the oedema by 70 +/- 12%, 65 +/- 10%
      and 61 +/- 19%, respectively, at t = 30 min. Aqueous enzyme solutions and empty
      carriers had no such effect. The combination of two enzymes resulted in no
      increased therapeutic effect, but the results are inconclusive since only two
      dose combinations were tested. The results presented in this study suggest that
      antioxidant enzymes delivered by means of ultradeformable lipid vesicles can
      serve as a novel region-specific treatment of inflammation.

PMID- 19839800
TI  - Preparation and characterization of vitamin-12 loaded biodegradable pH-sensitive
      microgels.
AB  - This paper prepared novel biodegradable and pH-sensitive microgels based on
      Poly(epsilon-caprolactone)-Pluronic-Poly(epsilon-caprolactone)-dimethacrylate
      (PCFC-DMA), Poly(ethylene glycol) dimethacrylate (PEG-DMA) and methylacrylic acid
      (MAA) cross-linked with N,N'-methylenebisacrylamide (BIS), initiated by NaHSO(3),
      K(2)S(2)O(8). The blank microgels were prepared by inversed-phase suspension
      polymerization method and pH sensitivity of microgels was characterized. Then the
      blank microgels were loaded with hydrophilic model drug vitamin-12 (VB-12) and in
      vitro drug release behaviour was also studied here.

PMID- 19839803
TI  - The future of theranostic nanoagents.

PMID- 19839802
TI  - Shell-cross-linked amino acid-modified APLA-b-PEG-Cys copolymer micelle as a drug
      delivery carrier.
AB  - Cysteine modified amphiphilic block copolymer acetate-polylactide-block
      poly(ethylene glycol)-Cysteine (APLA-b-PEG-Cys) was synthesized and
      characterized. The polymer could self-assemble to form micelles with nano-size
      and regularly spherical in shape in aqueous solution. Folic acid (FA) was then
      used as a model drug to incorporate into APLA-b-PEG-Cys micelles. To enhance the
      stabilization of APLA-b-PEG-Cys micelle and control the drug release, the shell
      of APLA-b-PEG-Cys micelle was cross-linked by the in situ polycondensation of
      amino acid moieties on its surface. The effects of shell-cross-linking on the
      micelle physical chemistry properties were investigated in detail. It was found
      that, after cross-linking, the CMC of the APLA-b-PEG-Cys micelle was decreased,
      indicating that the shell-cross-linked micelle is more stable as compared to the
      uncross-linked one. In addition, the shell-cross-linking also changed the surface
      potential, micelle size and model drug (FA) release behaviour, but it did not
      significantly affect the micelle morphology and drug encapsulation efficiency of
      APLA-b-PEG-Cys micelles.

PMID- 19839806
TI  - Conference scene: 2nd annual European conference for clinical nanomedicine.

PMID- 19839807
TI  - Conference scene: innovative medical devices and nanotechnology: 1-day
      interactive workshop.

PMID- 19839808
TI  - Efficacy of niosomal formulation of diallyl sulfide against experimental
      candidiasis in Swiss albino mice.
AB  - AIM: We developed a niosomal formulation of diallyl sulfide (DAS), a garlic oil
      component, and evaluated its efficacy against experimental candidiasis in mice.
      METHODS: DAS-bearing niosomes prepared from sorbitan monoester surfactants were
      evaluated for drug entrapment efficiency, release kinetics, toxicity, size, zeta
      potential and others. Mice challenged with Candida albicans were treated with
      various DAS formulations. The efficacy of the formulations was assessed on the
      basis of reduction in mortality and decrease in residual fungal load in vital
      organs, such as liver and spleen, of treated mice. RESULTS: Niosomal DAS (12
      mg/kg body weight) significantly reduced fungal load and mortality in treated
      animals compared with the free form of DAS. Niosomal DAS was also found to be
      free of toxic manifestations, as revealed by histopathological studies, as well
      as liver/kidney function tests. CONCLUSION: Incorporation of DAS in niosomes
      enhances its antifungal efficacy. Further studies are needed to optimize the
      current findings to develop an efficient nature-derived alternative antifungal
      therapeutic strategy.

PMID- 19839809
TI  - Biologic nanoparticles and platelet reactivity.
AB  - AIM: Nanosized particles (NPs) enriched in hydroxyapatite and protein isolated
      from calcified human tissue accelerate occlusion of endothelium-denuded arteries
      when injected intravenously into rabbits. Since platelet aggregation and
      secretory processes participate in normal hemostasis, thrombosis and vascular
      remodeling, experiments were designed to determine if these biologic NPs alter
      specific platelet functions in vitro. METHODS: Platelet-rich plasma was prepared
      from citrate anticoagulated human blood. Platelet aggregation and ATP secretion
      were monitored in response to thrombin receptor agonists peptide (10 microM) or
      convulxin (50 microg/ml) prior to and following 15 min incubation with either
      control solution, human-derived NPs, bovine-derived NPs or crystals of
      hydroxyapatite at concentrations of 50 and 150 nephelometric turbidity units.
      RESULTS: Incubation of platelets for 15 min with either human- or bovine-derived
      NPs reduced aggregation induced by thrombin receptor activator peptide and
      convulxin in a concentration-dependent manner. Hydroxyapatite caused a greater
      inhibition than either of the biologically derived NPs. Human-derived NPs
      increased ATP secretion by unstimulated platelets during the 15 min incubation
      period. CONCLUSION: Effects of bovine-derived and hydroxyapatite NPs on basal
      release of ATP were both time and concentration dependent. These results suggest
      that biologic NPs modulate both platelet aggregation and secretion. Biologically
      derived NPs could modify platelet responses within the vasculature, thereby
      reducing blood coagulability and the vascular response to injury.

PMID- 19839810
TI  - Platelet compatibility of PLGA, chitosan and PLGA-chitosan nanoparticles.
AB  - AIM: The increasing interest in biodegradable nanoparticles containing
      biomaterials such as poly(D,L-lactide-co-glycolide) (PLGA) and chitosan for drug
      delivery raises issues regarding the blood compatibility of these nanoparticles,
      since some nanoparticles, including carbon nanoparticles, can affect human
      platelet aggregation and cause vascular thrombosis. Therefore, the aim of this
      work was to investigate the effect of polymeric nanoparticles on human platelet
      function by measuring aggregation and receptor expression in vitro. MATERIALS &
      METHOD: PLGA, chitosan-PLGA and a series of chitosan nanoparticles were prepared
      by the single emulsion technique and ionotropic gelation method. The effects of
      these nanoparticles (0.01-100 microg/ml) on resting platelets, as well as on
      platelet aggregation and expression of receptors (GPIIb/IIIa and P-selectin)
      induced by agonists in platelet-rich plasma were examined using light
      aggregometry and flow cytometry. RESULTS & CONCLUSION: All tested nanoparticles
      at concentrations below 10 microg/ml did not modify platelet aggregation, showing
      that they may be used for the delivery of active molecules to the bloodstream.

PMID- 19839811
TI  - Imaging and organelle distribution of fluorescent InGaP/ZnS nanoparticles in
      glial cells.
AB  - AIM: To assess the effects of oleic acid treatment on subcellular distribution of
      indium gallium phosphide-zinc sulfide (InGaP/ZnS) nanoparticles in microglia and
      astrocytes. MATERIALS & METHODS: The extent of colocalization between the
      nanoparticles and organelles was assessed by confocal microscopy,
      spectrofluorometry and cell sorting. RESULTS: Cell treatment with a common fatty
      acid (oleic acid) within the range of physiological concentrations markedly
      enhanced the InGaP/ZnS uptake by microglia and afforded their colocalization
      within lipid droplets/lysosomes but not with mitochondria. CONCLUSION: These
      results suggest that the availability of mono-unsaturated fatty acids, such as
      oleic acid, in different cells could significantly alter nanoparticle uptake and
      localization, which can in turn affect the functions of cells and tissues
      coexposed to nanoparticles.

PMID- 19839812
TI  - Imaging the distribution of individual platinum-based anticancer drug molecules
      attached to single-wall carbon nanotubes.
AB  - AIMS: To image the distribution of drug molecules attached to single-wall carbon
      nanotubes (SWNTs). MATERIALS & METHODS: Herein we report the use of scanning
      transmission electron microscopy (STEM) for atomic scale visualization and
      quantitation of single platinum-based drug molecules attached to SWNTs designed
      for targeted drug delivery. Fourier transform infrared spectroscopy and energy
      dispersive x-ray spectroscopy were used for characterization of the SWNT drug
      conjugates. RESULTS: Z-contrast STEM imaging enabled visualization of the first
      line anticancer drug cisplatin on the nanotubes at single molecule level. The
      identity and presence of cisplatin on the nanotubes was confirmed using energy
      dispersive x-ray spectroscopy and Fourier transform infrared spectroscopy. STEM
      tomography was also used to provide additional insights concerning the nanotube
      conjugates. Finally, our observations provide a rationale for exploring the use
      of SWNT bioconjugates to selectively target and kill squamous cancer cells.
      CONCLUSION: Z-contrast STEM imaging provides a means for direct visualization of
      heavy metal containing molecules (i.e., cisplatin) attached to surfaces of carbon
      SWNTs along with distribution and quantitation.

PMID- 19839813
TI  - Optimization of physicochemical parameters influencing the fabrication of protein
      loaded chitosan nanoparticles.
AB  - AIM: In the development of controlled-release protein therapeutics, the high
      encapsulation of proteins into biodegradable nanoparticles with uniform size in
      an anhydrous process along with an excellent redispersion is of practical
      interest. The objective of this work was to study the physicochemical and in
      vitro release properties of chitosan nanoparticles with different molecular
      weights (low, medium and high) using bovine serum albumin (BSA) as a model
      protein for developing nanoparticle formulations that were stable and
      reproducible after lyophilization. MATERIALS & METHODS: The BSA-loaded chitosan
      nanoparticles were prepared by an ionic gelation method using pentasodium
      tripolyphosphate as the polyanions. The physicochemical properties and in vitro
      release kinetics of the nanoparticles were evaluated along with Fourier transform
      infrared spectroscopy studies. Furthermore, the nanoparticles were freeze-dried
      for long-term stability in the formulation. To optimize the size of the freeze
      dried nanoparticles after redispersion, various types of lyoprotectants (natural
      and synthetic) were tested in varying concentration in the process of
      lyophilization. RESULTS: The dynamic light scattering measurements revealed the
      increase in size of chitosan nanoparticles with the increase in molecular weight
      of chitosan with no significant change, irrespective of the concentration of BSA
      entrapped. In addition, the entrapment efficiency of the nanoparticles increased
      with the increasing molecular weight of chitosan and BSA concentration. By
      contrast, the redispersity of the freeze-dried samples resulted in further
      increase of the mean diameter of the nanoparticles. CONCLUSION: Among the various
      types of lyoprotectants (natural and synthetic) examined, sucrose proved to be
      very effective in reducing the size of freeze-dried nanoparticles on redispersion
      without significant change in surface charge of nanoparticles. Finally, the in
      vitro release kinetics of BSA from nanoparticles of different molecular weights
      of chitosan, with and without sucrose, was evaluated and found to depend upon the
      molecular weight of chitosan.

PMID- 19839814
TI  - High-strength metal nanomagnets for diagnostics and medicine: carbon shells allow
      long-term stability and reliable linker chemistry.
AB  - The rapidly growing applications of nanomagnets in magnetic drug delivery and
      separation in clinical diagnostics require strong and reliable magnetic vehicles.
      Strength conveys rapid processing, high delivery/targeting yield and rapid
      results when used in clinics. Reliability enables recycling of nanomagnets,
      regulatory-conforming drug formulations and efficient use of (expensive)
      antibodies in diagnostics, combined with reduced leaching (reagent loss). The
      present work illustrates how metal-based nanomagnets provide a two-three-times
      stronger magnetic particle than conventional magnetite-based materials. Ligands,
      antibodies or drugs can be anchored to such carbon/metal core/shell nanomagnets
      over covalent, hydrolysis-resistant carbon-carbon bonds. This linker chemistry
      resists strong acids, sterilization and prolonged storage or aggressive
      treatment. As dispersions, functional nanomagnets rapidly scan liquids/tissue by
      Brownian diffusion, capture/deliver/react at a target and are efficiently
      recollected after use. Metal iron-based, carbon-coated nanomagnets consist of
      particularly well-accepted materials and now open stable nanomagnets to a broad
      range of fascinating separation problems in biomedical research.

PMID- 19839815
TI  - Magnetically modulated nanosystems: a unique drug-delivery platform.
AB  - Magnetic nanoparticles are attractive targets owing to their unique
      characteristics that are not shared by bulk materials. Magnetic particles,
      ranging from nanometer-sized to 1 microm in size, are being used in an increasing
      number of medical applications. The important properties of magnetic particles
      for medical applications are nontoxicity, biocompatiblilty, injectability and
      high-level accumulation in the target tissue or organ. Magnetic nanoparticles
      modified with organic molecules have been widely used for biotechnological and
      biomedical applications as their properties can be magnetically controlled by
      applying an external magnetic field. They offer high potential for numerous
      biomedical applications, such as cell separation, automated DNA extraction, gene
      targeting, drug delivery, MRI and hyperthermia. When coated with, for example, an
      antibody, they can be applied in highly sensitive immunoassays or small substance
      recoveries. Furthermore, a novel application of magnetic nanoparticles and
      magnetic forces for tissue engineering, termed 'magnetic force-based tissue
      engineering' has been proposed. Particular attention had been paid to the
      preparation methods that allow the synthesis of particles of nearly uniform size
      and shape.

PMID- 19839818
TI  - Residual daily urine volume association with inflammation and nutrition status in
      maintenance hemodialysis patients.
AB  - BACKGROUND: This study determines the clinical significance of residual renal
      function (RRF), defined as residual daily urine volume (RDUV), in maintenance
      hemodialysis (MHD) patients. METHODS: This multi-center study enrolled 704 MHD
      patients. Geographic, hematological, biochemical, and dialysis-related data were
      obtained. Values for nutritional and inflammatory markers were analyzed together
      with RDUV. RESULTS: In total, 670 of 704 patients (95.2%) with HD duration
      greater than 1 year had abnormal RDUV (<500 ml). Patients with higher RRF were
      younger, had shorter HD duration, higher prevalence of hypertension and levels of
      serum albumin, high density lipoprotein (HDL), and lower mid-week inter-dialysis
      body weight increase (MIBWI), cardio-thoracic ratio, levels of intact parathyroid
      hormone, high sensitivity C-reactive protein (Hs CRP), and KT/V (Daugirdes)
      values than those with low RRF. Stepwise multiple regression analysis
      demonstrated that RRF was positively correlated with serum albumin, HDL levels,
      and presence of hypertension, and negatively correlated with age, HD duration,
      and MIBWI in MHD patients. Moreover, after adjusting factors that were
      significantly related to serum albumin or Hs CRP, RRF was still positively
      correlated with serum albumin (0.000137 +/- 0.000585, p = 0.0197) and negatively
      correlated with log Hs CRP (-0.000184 +/- 0.000952, p = 0.0533). A one-liter
      increase in RDUV was associated with a 1.4 g/L increase in serum albumin level in
      MHD patients. CONCLUSION: This clinical study first demonstrated that RRF affects
      nutritional and inflammatory status in MHD patients. Because malnutrition and
      inflammation can cause high mortality in MHD patients, preserving RRF is
      important for these patients.

PMID- 19839819
TI  - Acute renal failure in hospitalized patients in China: a prospective study.
AB  - Acute renal failure (ARF) is a common complication in hospitalized patients, but
      little is known about the epidemiology of ARF in China. In this study, we
      performed a prospective examination of the cause, prognosis, and risk factors
      associated with ARF at a hospital in Shanghai, China. We considered all ARF
      patients who were admitted to our hospital from December 2003 to December 2006.
      Among the 320 ARF patients, 135 (42.2%) were over the age of 60. Sepsis, heart
      failure, and nephrotoxic drug use were the leading causes of ARF. The overall
      mortality rate was 31.9%, and mortality rate was significantly higher among the
      elderly. Logistic regression indicated that heart failure, respiratory failure,
      and malignant cancer were risk factors independently associated with poor
      prognosis. In this Shanghai hospital, there was a high incidence and mortality
      rate of patients hospitalized with ARF. The prognosis of patients who underwent
      renal replacement therapy was better than those who were treated more
      conservatively.

PMID- 19839816
TI  - Plasmonic nanoparticle-generated photothermal bubbles and their biomedical
      applications.
AB  - This article is focused on the optical generation and detection of photothermal
      vapor bubbles around plasmonic nanoparticles. We report physical properties of
      such plasmonic nanobubbles and their biomedical applications as cellular probes.
      Our experimental studies of gold nanoparticle-generated photothermal bubbles
      demonstrated the selectivity of photothermal bubble generation, amplification of
      optical scattering and thermal insulation effect, all realized at the nanoscale.
      The generation and imaging of photothermal bubbles in living cells (leukemia and
      carcinoma culture and primary cancerous cells), and tissues (atherosclerotic
      plaque and solid tumor in animal) demonstrated a noninvasive highly sensitive
      imaging of target cells by small photothermal bubbles and a selective mechanical,
      nonthermal damage to the individual target cells by bigger photothermal bubbles
      due to a rapid disruption of cellular membranes. The analysis of the plasmonic
      nanobubbles suggests them as theranostic probes, which can be tuned and optically
      guided at cell level from diagnosis to delivery and therapy during one fast
      process.

PMID- 19839820
TI  - Elevated plasma levels of PAI-1 predict cardiovascular events and cardiovascular
      mortality in prevalent peritoneal dialysis patients.
AB  - BACKGROUND: Elevated plasminogen activator inhibitor-1 (PAI-1) levels are
      associated with increased cardiovascular (CV) risk in the general population. It
      has been shown that peritoneal dialysis (PD) patients have increased plasma
      levels of PAI-1. The aim of this study was to investigate whether PAI-1
      independently predicted CV outcome in PD patients. MATERIAL AND METHODS: Seventy
      two PD patients (53% females, mean age 49.9 +/- 16.1 years) were studied. Twelve
      patients who underwent kidney transplantation and 14 patients who transferred to
      hemodialysis during follow-up were excluded from the analysis. The remaining 46
      patients (54% female, mean age 54 +/- 16 years, dialytic age 42 +/- 30 months)
      were followed a mean time of 45.4 +/- 19.4 months (range 8-71 months). Baseline
      PAI-1, clinical, and laboratory parameters were assessed in all patients.
      Survival analyses were made with Kaplan-Meier and Cox regression analysis, with
      all-cause mortality and CV mortality and CV events (CVEs) as clinical end points.
      RESULTS: During the follow-up, 29 patients died (17 from CV causes), and 28 fatal
      and non-fatal CVEs were recorded. The patients were divided according to plasma
      PAI-1 levels (i.e., <or= or >41 ng/mL). The significant independent predictors of
      all-cause of mortality were age (60 years; p = 0.018), CRP (5 mg/L; p = 0.015),
      and serum albumin (<3.5 g/L; p = 0.011). Multivariable Cox regression analysis
      showed that plasma PAI-1 41 ng/mL was independently predictive of higher CV
      mortality (p = 0.021) and CVEs (p = 0.001). The only other independent predictor
      of CV mortality was only CRP (5 mg/L; p = 0.008). CONCLUSIONS: Plasma levels of
      PAI-1 41 ng/mL is a significant predictor of CV mortality and CVEs in PD
      patients.

PMID- 19839821
TI  - IgA nephropathy associated with thin basement membrane with or without
      inflammatory disease: getting a different prognosis?
AB  - BACKGROUND: Thin basement membrane nephropathy (TBMN) patients with additional
      inflammatory diseases and IgA nephropathy (IgAN) have not been reported before.
      It was unclear that if the prognosis of these patients is better or worse than
      patients with IgAN and TBMN, or IgAN patients with normal glomerular basement
      membrane (GBM). METHODS: We first reported five TBMN patients with additional
      inflammatory diseases and IgAN: three were with rheumatoid arthritis, and two had
      Crohn's disease. Clinical and laboratory features were analyzed between this
      group (group 3), IgAN patients with normal GBM (group 1), and patients with TBMN
      and IgAN (group 2). RESULTS: Significant differences were observed in serum
      levels of IgG, IgA, and IgM between groups 1 and 3, p < 0.001, and between groups
      2 and 3, p < 0.001. Glomerular filtration rate (GFR) in group 3 was significantly
      lower than that of groups 1 and 2, p < 0.01, respectively. CONCLUSION: The
      prognosis of these patients is worse than patients with IgAN and TBMN or IgAN
      patients with normal GBM. Serum immunoglobulin levels and GFR in these patients
      were different from patients with IgAN and TBMN, or IgAN patients with normal
      GBM.

PMID- 19839822
TI  - Markers of tubular and glomerular injury in predicting acute renal injury outcome
      in thermal burn patients: a prospective study.
AB  - BACKGROUND/AIM: Thermal injury elicits several systemic consequences. Acute renal
      failure (ARF) is a well-known complication of severe burn and is an important
      factor leading to an increase in mortality. We aimed to focus on early diagnosis
      of acute renal failure occurring in major burns and to determine the predictors
      for acute renal failure. SUBJECTS AND METHODS: Forty patients with moderate to
      severe thermal burn injury--second- to third-degree with >20% of total body
      surface area--constituted the material of our study. The following parameters
      were recorded: age, sex, cause of the burn injury, burn surface of second and
      third degrees expressed as total body surface area burned in %, and Apache II
      score. All patients were subjected to routine investigations, including serum
      creatinine, blood urea nitrogen, fractional excretion of sodium, urinary
      malondialdehyde and microalbuminuria, completed on days 0, 3, 7, 14 and 21.
      RESULTS: Nine patients (22.5% of all cases) developed acute renal failure, and
      four patients required supportive dialysis. The group that developed ARF showed
      rising markers of glomerular damage with appearance of microalbuminuria on day 0
      that was maximal (3-4 times its normal level) at day 14 and constant with
      elevated serum creatinine, as well as burn size in the third week that progressed
      to overt proteinuria in three cases. Urinary malondialdehyde was also elevated
      before developing acute renal failure about three times their normal values,
      gradually increasing on day 14, associated with rising microalbuminuria followed
      by its decrease after controlling of septicemia. Two cases (22.2%) in ARF group
      who developed septicemia and required dialysis died on the 32(nd) and 36(th) days
      post-burn. Burn size and occurrence of septicemia were the only predictors of
      acute renal failure using multiple regression analysis (SE B 0.003 and 0.104; p
      value of 0.001 and .0371, respectively). CONCLUSIONS: Acute renal failure, which
      complicates 22.5% of burn patients, was found to be related to the size and depth
      of burn. Microalbuminuria and urinary malondialdehyde are useful markers for
      prediction of renal outcome in such group of patients. In our study. burn size
      and septicemia proved to be the only clinical parameters that predict renal
      outcome.

PMID- 19839823
TI  - Effects of rosiglitazone on cardiac function in CAPD patients: a tissue Doppler
      study.
AB  - BACKGROUND: Insulin resistance was an independent predictor of cardiovascular
      mortality in uremic patients without diabetes. Rosiglitazone (ROS) improves
      insulin sensitivity in the liver, muscle, and adipose tissue. We prospectively
      investigated the effects of ROS on cardiac functions by standard (SDE) and tissue
      Doppler echocardiography (TDI) in continuous ambulatory peritoneal dialysis
      (CAPD) patients. METHODS: A total of 24 CAPD patients (13 males, 11 females; mean
      age 42.2 +/- 14.8 years) were included. Routine blood samples were examined. Left
      and right ventricular functions were assessed, and myocardial performance index
      (MPI) was calculated by SDE and TDI at baseline and after 12-month ROS therapy.
      Left and right atrial volumes were measured and indexed to body surface area.
      RESULTS: When compared with baseline, after 12 months of ROS treatment, it was
      shown that early (E) and late (A) diastolic velocities of atrioventricular
      valves, E/A ratio, mitral E-wave deceleration time (DT), isovolumetric relaxation
      time (IVRT), and MPI were similar (p > 0.05). Also, no significant changes were
      detected in LV dimensions, LV mass index, LVEF, LA volume index, or RA volume
      index measured by SDE before and after ROS therapy (p > 0.05). Left and right
      ventricular function parameters measured by TDI including Sm, Em, Am, Em/Am
      ratio, E/Em ratio, and MPI were similar. CONCLUSION: It was found that there was
      no negative effect of long-term ROS therapy on cardiac functions measured by SDE
      and TDI in CAPD patients.

PMID- 19839825
TI  - Cell-free plasma DNA during Hemodialysis.
AB  - PURPOSE: Cell-free plasma DNA (cfDNA) levels originating predominantly from
      apoptotic leukocytes were found to rise during hemodialysis (HD) session, and as
      such are considered a marker of HD membrane biocompatibility. The purpose of our
      study was to determine the changes of cfDNA during two consecutive high-flux
      polysulphone HD sessions after a long (HD-L) and short (HD-S) interdialytic
      interval. METHODS: A total of 17 HD patients were examined. Prior to HD and at 30
      and 240 min, cfDNA (using real-time PCR) and leukocyte count were determined.
      RESULTS: No significant difference was found when comparing pre-HD-S with pre-HD
      L cfDNA [4893 (1090-28804) vs. 4589 (691-73796) genomic equivalent/mL]. A
      significant increase in cfDNA at 240 min was seen in HD-L (p < 0.05) but not in
      HD-S. Leukocyte count correlated with cfDNA levels before HD-S (r = 0.8; p <
      0.01); however, no other correlation was seen between routinely measured
      biochemical markers and pre-HD cfDNA levels or cfDNA changes during HD. The
      increase in plasma cfDNA during HD did not correlate with dialysis duration, its
      efficacy, or ultrafiltration. An association between magnitude of diuresis and
      cfDNA levels in HD-S was found (r = 0.58; p < 0.05). CONCLUSIONS: The behavior of
      cfDNA during HD after long and short interdialytic interval is inconsistent and
      cannot be explained by changes in laboratory and clinical parameters. The
      observed relationship of plasma cfDNA levels with diuresis deserves further
      investigation.

PMID- 19839824
TI  - Metabolic factors and microinflammatory state promote kidney injury in type 2
      diabetes mellitus patients.
AB  - OBJECTIVE: This study examined the associations among the factors of metabolic
      syndrome, microinflammatory state, and kidney injury in type 2 diabetes mellitus
      patients. METHODS: A retrospective study was conducted on 914 type 2 diabetes
      mellitus patients from January 2007 to May 2008. We observed the prevalence of
      chronic kidney disease in different groups of type 2 diabetes mellitus patients,
      and analyzed the association between metabolic syndrome and chronic kidney
      disease. We chose 84 cases randomly from this cohort to test their inflammatory
      biomarkers including tumor necrosis factor alpha, interleukin-6, and C-reactive
      protein to study the relationship to chronic kidney disease. RESULTS: The
      prevalence of chronic kidney disease was 39.17% (358 patients), and patients with
      metabolic factors had a significantly higher prevalence of chronic kidney disease
      than without metabolic factors (40.90% vs. 17.65%, p < 0.01). The metabolic
      factors and microinflammatory biomarkers were significantly higher in patients
      with chronic kidney disease. Patients who had more abnormal metabolic factors
      also had higher levels of microinflammatory biomarkers, as well as higher risk of
      chronic kidney disease. Multiple logistic regression analyses revealed that
      systolic blood pressure, serum triglyceride, low density lipoprotein, age, and
      duration of diabetes were independent risk factors of chronic kidney disease in
      type 2 diabetes mellitus patients. CONCLUSIONS: The abnormality of metabolic
      factors in type 2 diabetes mellitus had a close relationship to the
      microinflammatory state and chronic kidney disease. Hypertension and
      hyperlipidemia were independent factors of chronic kidney disease in type 2
      diabetes mellitus.

PMID- 19839826
TI  - Renal effects of plant-derived oleanolic acid in streptozotocin-induced diabetic
      rats.
AB  - Previous studies from our laboratories indicate that the anti-diabetic effects of
      Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in streptozotocin-induced
      diabetic rats may be attributed in part to mixtures of triterpenes, oleanolic
      acid (3ss-hydroxy-olea-12-en-28-oic acid, OA) and ursolic acid (3ss -hydroxyl-urs
      12-en-28-oic acid, UA). For the bioactive compounds to have potential in diabetes
      management, they should alleviate or prevent complications of diabetes mellitus,
      kidney function, and cardiovascular disorders. This study was, therefore,
      designed to assess whether S. cordatum leaf derived OA influenced renal function
      evaluated by the ability to increase urinary Na(+) outputs parameters and
      creatinine clearance (Ccr) of streptozotocin (STZ)-induced diabetic rats.
      Extraction and fractionation of S. cordatum powdered leaf ethyl acetate-solubles
      (EAS) yielded mixtures of OA/UA and methyl maslinate/methyl corosolate.
      Recrystallization of OA/UA mixture using ethanol afforded OA, the structure of
      which was confirmed by NMR spectroscopy ((1)H & (13)C). Acute effects of OA on
      kidney function and mean arterial blood pressure (MAP) were investigated in
      anesthetized rats challenged with hypotonic saline after a 3.5-h equilibration
      for 4h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. OA was added
      to the infusate during the treatment period. Chronic effects of OA were studied
      in individually caged rats treated twice daily with OA (60 mg/kg, p.o.) for five
      weeks. By comparison with respective control animals administration, OA
      significantly increased Na(+) excretion rates of non-diabetic and STZ-induced
      diabetic rats without affecting urine flow, K(+) and Cl(-) rates. At the end of
      five weeks, OA treatment significantly (p < 0.05) increased Ccr in non-diabetic
      (2.88 +/- 0.14 vs. 3.71 +/- 0.30 ml/min) and STZ-diabetic rats (1.81 +/- 0.32 vs.
      3.07 +/- 0.16 ml/min) with concomitant reduction of plasma creatinine
      concentration (n = 6 in all groups). OA also caused significant decreases in MAP
      in non-diabetic and STZ-induced diabetic rats. These findings suggest that OA may
      have beneficial effects on some processes associated with renal derangement of
      STZ-induced diabetic rats.

PMID- 19839827
TI  - In vitro differentiation of MSC into cells with a renal tubular epithelial-like
      phenotype.
AB  - Bone marrow mesenchymal stem (stromal) cells (MSCs) are shown to differentiate
      into different renal lineages in in vivo injury models. Nevertheless, the in
      vitro differentiation of MSCs into a renal tubular epithelial lineage has not
      been investigated. We hypothesize that the injured renal epithelial cells express
      renotypic factors that may influence the differentiation of MSCs into a renal
      tubular epithelial lineage. MSCs were cocultured for up to seven days with
      injured or uninjured murine cortical tubular renal epithelial cells (MCTs), which
      are separated by a physical barrier; following the coculture, MSCs were examined
      for the expression of two renal tubular epithelial-specific markers, kidney
      specific cadherin (Ksp-cadherin) and aquaporin-1 (AQP1). MSCs differentiated into
      a tubular epithelial-like phenotype, as shown by the appearance of Ksp-cadherin
      and AQP1 by day 7 when cocultured with injured MCTs. Further, MSCs showed
      tubulogenic characteristics when cocultured in a three-dimensional matrix.
      Nonetheless, MSCs cultured with the conditioned medium from injured MCTs,
      cocultured with ureteric bud cells, or treated with nephrogenic factors did not
      differentiate into renal epithelial cells. Based on our findings, we conclude
      that MSCs can differentiate into a renal epithelial lineage independent of cell
      fusion when cocultured with injured renal cells.

PMID- 19839829
TI  - Hyperoxia-induced protection against rat's renal ischemic damage: relation to
      oxygen exposure time.
AB  - BACKGROUND: Pre-exposure to hyperoxic gas (>or= 95%) has been shown to protect
      the heart and central nervous system from ischemia-reperfusion injury. In the
      present study, we investigated whether oxygen pretreatment induces delayed renal
      protection in rats. The possible role of some renal antioxidant agents was also
      investigated. MATERIALS AND METHODS: Adult male Wistar rats were kept in a
      hyperoxic (HO) (>or= 95% O(2)) environment for 0.5 h, 1 h, 2 h, 3 h, 6 h, and 2
      h/day for three consecutive days and 4 h/day for six consecutive days, and
      control group (IR) animals were kept in the cage with no HO, one day before
      subjecting their kidney to 40 minutes of ischemia and 24h of reperfusion. Renal
      function was assessed by comparing plasma creatinine (Cr), blood urea nitrogen
      (BUN), creatinine clearance (CLCr), and fractional excretion of sodium (FENa%).
      Histopathological injury score was also determined according to the Jablonski
      method. To examine the antioxidant system induction by hyperoxia, we measured
      renal catalase and superoxide dismutase activity, and renal glutathione and
      malondialdehyde content. RESULTS: Our data demonstrated that only in 4 h/day HO
      for six consecutive days, the renal function tests (Cr, CLCr, BUN, and FENa%) and
      Jablonski histological injury were better than control group (p < 0.05). The
      beneficial effect of oxygen pretreatment in this group was associated with
      increased renal catalase activity compared with those obtained from control group
      (p < 0.05). CONCLUSION: The present study demonstrates that repeated exposure to
      hyperoxic (>or= 95% O(2)) environment can reduce subsequent rat's renal ischemia
      reperfusion damage. Induction of endogenous antioxidant system may partially
      explain this beneficial effect of hyperoxic preconditioning.

PMID- 19839828
TI  - Simvastatin reverses podocyte injury but not mesangial expansion in early stage
      type 2 diabetes mellitus.
AB  - Statins may confer renal protection in a variety of glomerular diseases,
      including diabetic nephropathy (DN). However, various glomerular lesions have
      different etiologies and may have different responses to statins. This study was
      performed to determine the differential effects of simvastatin (SMV) on
      glomerular pathology including mesangial expansion and podocyte injury in a mouse
      model of early stage type 2 diabetes mellitus (DM). Type 2 DM was induced in male
      C57BL/6 mice by feeding a high fat diet (HF; 45 kcal% fat). After 22 weeks, one
      group of HF mice was treated with SMV (HF-SMV; 7 mug/day/g BW) and another group
      was treated with vehicle (HF-vehicle) for 4 weeks via osmotic mini-pump. A third
      group served as age-matched normal diet vehicle controls (ND-vehicle; 10 kcal%
      fat). At the end of treatment, glomerular morphology was evaluated in a blind
      manner to determine the progression of DN. Body weight, blood glucose, insulin,
      HDL-cholesterol and triglycerides, but not LDL-cholesterol, were increased in HF
      mice. Over the course of treatment, the 24-hour urinary albumin excretion (UAE)
      was unchanged in ND-vehicle. HF mice exhibited elevated UAE, which decreased with
      SMV, but was unchanged with vehicle. The absolute mesangial volume and the
      relative mesangial volume per glomerular volume increased in HF-vehicle and
      remained elevated with SMV treatment. The immuno-staining of nephrin, a protein
      marker of the integrity of podocyte slit diaphragms, was decreased in HF-vehicle;
      however, the nephrin quantity of the HF-SMV group was not different from ND
      vehicle. It is concluded that SMV reverses podocyte damage, but does not affect
      mesangial expansion in the kidneys of early stage proteinuria of type 2 DM.

PMID- 19839830
TI  - Effects of pomegranate juice on hyperoxaluria-induced oxidative stress in the rat
      kidneys.
AB  - To evaluate the role of the inducible nitric oxide synthase (iNOS), selective
      nuclear factor-kB (NF-kB), and p38-mitogene-activated protein kinase (p38-MAPK)
      on hyperoxaluria-induced oxidative stress and stone formation in rat kidneys. The
      rats were divided into five groups: group 1, control group; group 2: ethylene
      glycol (EG) group; group 3: EG + pomegranate juice (PJ)-low group; group 4: EG +
      PJ-middle group; group 5: EG + PJ-high group. Rats were sacrificed on 7, 15, and
      45 days. The iNOS expression, p65-NF-kB and p38-MAPK activity, and oxidative
      stress markers were evaluated in the kidney. Crystal depositions were evident on
      day 7, and mild and severe crystallization were observed on day 15 and 45 in EG
      group, respectively. There was limited or no crystal formation in rats in both
      middle- and high-dose PJ groups when compared to low-dose PJ group. Crystal
      depositions, iNOS, p38-MAPK and p65-NF-kB activity, and oxidative stress markers
      were found to be decreased by middle- and high-dose PJ treatment. PJ was found to
      have inhibitory effects on renal tubular cell injury and oxidative stress caused
      by oxalate crystals by reducing ROS, iNOS, p38-MAPK, and NF-kB expression.

PMID- 19839831
TI  - Relation between serum urea and mortality of hemodialysis patients.
AB  - BACKGROUND: It is well known that serum urea concentration is not a good
      predictor of mortality in hemodialysis patients. On the other hand, urea kinetic
      modeling has been very successfully used to measure dialysis dose by the Kt/V
      index, which was found to be a good predictor of mortality. Could there be a
      relation between urea and mortality, but in some more complex way? METHODS: This
      is a post-hoc analysis of a single center observation study that included 242
      patients and an 11-year observation period. Mortality rates between the quartiles
      of serum urea levels were examined by a 2 x 4 table with the chi(2) test. Both
      univariate and multivariate survival analyses were performed with standard and
      segmented extended Cox regression. RESULTS: The relation between mean urea in the
      baseline period and mortality showed an irregular U-shaped curve. The lowest
      mortality was observed in the third quartile (28 to 31 mmol/L). The relation
      between mean urea in the whole observation period and mortality was a J-shaped
      curve. The lowest mortality was in the second quartile (25-27 mmol/L). Urea was
      not a predictor of mortality in the whole cohort, but low-urea (binary) and high
      urea (binary) were independent predictors of mortality in the corresponding
      models using standard or extended Cox regression. CONCLUSION: This study revealed
      a complex relationship between urea and mortality in hemodialysis patients.
      Patients with low or high urea levels exhibited higher mortality than those with
      medium levels, while both low and high levels of urea were independent predictors
      of all-cause mortality.

PMID- 19839832
TI  - Referral of patients with kidney impairment for specialist care in a developing
      country of sub-Saharan Africa.
AB  - AIM: The aim of this study was to assess the referral pattern of patients with
      kidney impairment in Cameroon. METHODS: Medical files of patients received at the
      out-patients department of nephrology from January 2001 to December 2003 at the
      Yaounde General Hospital were reviewed. Individual information recorded included
      age, sex, and referral sources. Data on etiologic and co-morbidity factors,
      clinical signs of CRF, anthropometric measurements, blood pressure, and
      biological variables were recorded. Patients were staged for kidney damage in
      three groups following an adaptation of the Kidney Disease Outcome Quality
      Initiative (KDOQI) guide recommendations, using the creatinine clearance derived
      from the Cockroft-Gault equation. RESULTS: Of the 183 patients received during
      the study period, 140 (77.8%) fulfilled the entry criteria. Men (70%) were more
      represented, and mean age was 50.19 +/- 1.07 years. Hypertension (62.1%) and
      diabetes mellitus (26.4%) were the most frequent risk factors. There was no major
      difference between men and women for most clinical and biological variables.
      Patients were referred mostly by cardiologist (31.4%) and general practitioners
      (29.3%). Late referral (GFR <30 mL/min) encompassed 82.8% of participants.
      Regardless of the referral source, the overall trend was toward late referral.
      Clinical and biological profiles worsen with advanced stage of kidney impairment.
      In general, management of patients prior to referral was poor. CONCLUSIONS: This
      study has revealed the disconcerting high rate of late referral to nephrologists
      in this context. Many potential factors can account for this observed pattern,
      and it is worth investigating to improve referral and outcomes of patients with
      kidney diseases in Cameroon.

PMID- 19839833
TI  - Effect of hepatitis C virus on hemoglobin and hematocrit levels in saudi
      hemodialysis patients.
AB  - BACKGROUND: Hepatitis C virus infection is common among patients undergoing
      hemodialysis, and HD patients are at high risk for infection with such virus.
      Recently, some studies and case reports indicated attenuated anemia in HD
      patients with HCV infection, and they previously considered this to be related to
      increased erythropoietin production after hepatic stimulation by chronic
      infection with hepatitis virus. AIM: The aim of our study is to investigate
      whether HCV-positive HD patients have higher hemoglobin (Hb) and hematocrit (HCT)
      values compared to HCV-negative patients. METHODS: We retrospectively studied 83
      chronic HD patients from Prince Salman Center for Kidney Disease, and monthly
      samples were collected between July 2007 and July 2008. The HCV status was
      determined by anti-HCV antibodies and confirmed with RNA polymerase chain
      reaction (PCR). Those with a history of blood transfusion or massive blood loss
      during the last six months were excluded from the study. RESULTS: Thirty-three
      percent of our patients tested positive for anti-HCV antibody (51.8% were male).
      The mean age for HCV-positive group was 54.92 +/- 15.61 years, while it was 51.01
      +/- 14.81 years for the HCV-negative group (p = 0.27). Mean Hb in the HCV
      positive group was 11.18 +/- 1.41 gm/dL compared to 10.87 +/- 1.29 gm/dL for the
      HCV-negative group (p = 0.05). Mean HTC values for the HCV-positive group was
      34.4 +/- 3.9, compared to 32.41 +/- 3.41 for the HCV-negative group 12 months
      after starting hemodialysis. Eighty-one patients (27 HCV-positive and 54 HCV
      negative) received erythropoietin (EPO) therapy. Seventy-two patients (25 HCV
      positive and 47 HCV-negative) received IV iron (p = 0.28). Mean erythropoietin
      dose was (114.83 +/- 84.92 IU/kg/week) for HCV-positive compared to (122.2 +/-
      91.46 IU/kg/week) for HCV-negative group (p = 0.74). Liver function tests were
      normal except for higher bilirubin level in the HCV-positive group, 7.74 +/- 4.03
      Umol/L compared to 5.47 +/- 3.71 Umol/L in the HCV-negative group (p = 0.01).
      CONCLUSION: Our study showed that ESRD patients on HD with HCV infection have
      higher Hb and HCT levels compared with HCV-negative patients.

PMID- 19839834
TI  - Is serum cystatin C an accurate endogenous marker of glomerular filteration rate
      for detection of early renal impairment in patients with type 2 diabetes
      mellitus?
AB  - BACKGROUND: Researches have recently reported that serum cystatin C is a more
      sensitive marker of changes in glomerular filtration rate (GFR) than serum
      creatinine. We conducted this study to evaluate the significance of serum
      cystatin C as a more sensitive marker of GFR for early detection of renal
      impairment in special groups of patients with type 2 diabetes mellitus (DM).
      METHODS: The present study included 40 patients with type 2 DM divided into four
      equal groups based on their urinary albumin excretion and renal function: group 1
      was normoalbuminuric, group 2 was microalbuminuric, group 3 was macroalbuminuric,
      and group 4 was macroalbuminuric with renal dysfunction. All patients underwent a
      thorough history, full clinical examination, fasting, and renal function tests.
      Post-prandial blood glucose levels, glycosylated hemoglobin A1c (HbA1c),
      proteins, albumin in 24 hr urine, and serum cystatin C were collected. RESULTS:
      Serum cystatin C and creatinine were significantly higher in macrolbuminuric type
      2 diabetic patients with renal dysfunction (group 4: 2.26 +/- 1.28, 4.21 +/- 2.38
      mg/dl, respectively; p < 0.001) than macrolbuminuric type 2 diabetic patients
      with normal renal function (group 3: 1.04 +/- 0.24, 0.96 +/- 0.20 mg/dl,
      respectively), the microalbuminuric group (0.87 +/- 0.28, 0.71 +/- 0.12 mg/dl,
      respectively), as well as the normoalbuminuric group (0.55 +/- 0.41, 0.60 +/-
      0.18 mg/dl, respectively). ROC plots demonstrated that area under the curve (AUC)
      of cystatin C (0.74) was greater than that for creatinine clearance (cr.cl)
      (0.67) and serum creatinine (s-cr) (0.74); therefore, the sensitivity and
      diagnostic accuracy of cystatin c was better than cr. cl., and both were better
      than s-cr. Serum cystatin C showed significant correlation in groups 2-4 with s
      cr, cr.cl, and 24 hr urine albumin, but no correlation was found in group 1.
      CONCLUSION: Serum cystatin C is a reliable and easily performed marker for GFR to
      detect renal impairment in patients with type 2 DM.

PMID- 19839835
TI  - Female sexual dysfunction in peritoneal dialysis and hemodialysis patients.
AB  - BACKGROUND: Sexual dysfunction (SD) is a common problem in end-stage renal
      disease (ESRD). In contrast to basic and clinical research in the field of male
      SD, the sexual problems of women have received relatively little attention and
      are often under-treated. We evaluated sexual function in female ESRD patients
      using the validated Female Sexual Function Index (FSFI) and relation with QOL,
      depression, and some laboratory parameters. METHODS: 117 ESRD patients (85
      peritoneal dialysis [PD], 32 hemodialysis [HD], mean age 48.5 +/- 13.9 years)
      were enrolled. All patients had been dialyzed (PD or HD) for more than three
      months. In addition, an age-matched married control group of 48 subjects (mean
      age 47.1 +/- 12.7 years) were enrolled in the study. All patients were asked to
      complete three questionnaires of the FSFI, Beck Depression Index (BDI) and SF-36.
      RESULTS: Female sexual dysfunction was found in 80 of the 85 peritoneal dialysis
      patients (94.1%) and all of the HD patients (100%), but in only 22 subjects of
      the control group (45.8%). A significant negative correlation was found between
      total FSFI score and age (r = -0.288, p = 0.002), BDI score (r = -0.471, p <
      0.001), mental-physical component score of QOL (r = -0.463, p < 0.001 and r = 
      0.491, p < 0.001, respectively) in PD and HD patients. The rates of depression
      were 75.3, 43.8, and 4.2% in the PD and HD patients and control subjects,
      respectively. CONCLUSION: Female sexual dysfunction is common problem ESRD. This
      problem especially related with depression and QOL. Thus, sexual function should
      be evaluated in female subjects to determine its impact on quality of life.

PMID- 19839836
TI  - New peritoneal dialysis model in rats with bilateral nephrectomy.
AB  - Many peritoneal dialysis (PD) patients with chronic renal failure (CRF) suffer
      from metabolic and nutritional abnormalities. However, these abnormalities have
      been not sufficiently investigated. At present, the resolution of these issues in
      this field has been hindered by the lack of suitable PD models. We attempt to
      develop a rat model of PD under no constraints and under non-anesthetization to
      evaluate amino acid solution as suitable nutritional therapy for renal failure.
      In our model, bilateral nephrectomy rats were dialyzed 6 h per day for three
      days. The dialysate was infused and removed continually via a metering pump.
      Under fasting, rats were infused with 5% glucose or amino acid solution for renal
      failure, and they remained alive. This model can be used to examine bilateral
      nephrectomy in rats for three or more days. We were also able to determine
      protein and calorie malnutrition, negative nitrogen balance, abnormalities in the
      plasma amino acid pattern, and calcium and phosphorus metabolism. Thus, this
      model has the characteristics of renal failure in humans and may be used to
      easily examine the metabolic changes due to loss of kidney function.

PMID- 19839837
TI  - Cyclosporine induces endothelin-1 mRNA synthesis and nitric oxide production in
      human proximal tubular epithelial cell cultures.
AB  - BACKGROUND: Cyclosporine (CsA) is implicated in the development of chronic
      allograft nephropathy, which is related to reduced long-term allograft survival.
      The activation of tubular epithelial cells is involved in the renal scarring
      process via stimulation of factors such as endothelin-1 (ET-1) and nitric oxide
      (NO). The effect of CsA on the activation of tubular epithelial cells towards
      increased production of ET-1 and NO was investigated in this study. METHODS:
      Human tubular epithelial cells (HK-2) were cultured in the presence of CsA at
      different concentrations (125, 250, 500, and 1,000 ng/mL). ET-1 m-RNA and NO
      production were measured using RT-PCR and Griess method, respectively. The
      cytotoxic effect of CsA was examined by the MTT method and cell count. RESULTS: A
      statistically significant and dose-dependent cytotoxic effect of cyclosporine on
      HK-2 cells was observed. A dose-dependent up-regulation of ET-1 mRNA production
      and NO accumulation was observed under the influence of CsA. CONCLUSION:
      Increased synthesis of endothelin-1 mRNA and nitric oxide as well as a
      significant cytotoxic effect on tubular epithelial cells under the influence of
      CsA might be related to the development of CsA nephrotoxicity.

PMID- 19839838
TI  - Possible effects of interferon-alpha on Fas-induced renal apoptosis in mouse.
AB  - Fas (APO-1/CD95) is a cell surface receptor that initiates apoptotic pathway. Fas
      stimulated ROS generation may play important role in Fas-mediated apoptosis. The
      aim of this study was to evaluate the influence of interferon-alpha on oxidative
      stress parameters in Fas-induced renal apoptosis in mice kidney. SUBJECTS AND
      METHODS: One-month-old Balb C male mice were used for the study. The animals were
      divided in four groups: group 1 were the controls, group 2 mice were treated with
      anti-Fas antibody i.p., group 3 mice were treated with IFN-alpha, and group 4
      mice were treated with both agents simultaneously. The mice were killed 48 h
      afterwards, and kidneys were homogenized. TBA reactive substances (TBARS),
      glutathione content, and reactive carbonyl group (RCG) were measured. RESULTS:
      The results showed a statistically significant increase of TBARS (p < 0.05) and
      RCG (p < 0.05) concentration in the group treated with anti-Fas antibody versus
      control. IFN-alpha decreased the concentration of TBARS and RCG after anti-Fas
      antibody administration (p < 0.05). There is no significant difference in
      glutathione content between investigated groups. CONCLUSION: IFN-alpha might be
      considered as a new target for therapeutic intervention in FasL/Fas induced renal
      injury.

PMID- 19839839
TI  - Atorvastatin prevents gentamicin-induced renal damage in rats through the
      inhibition of p38-MAPK and NF-kappaB pathways.
AB  - BACKGROUND AND AIMS: Gentamicin (GM) is still considered to be an important
      antibiotic against life-threatening, gram-negative bacterial infections despite
      its known nephrotoxic effects. We aimed to evaluate the potential protective
      effect of atorvastatin (ATO) against GM-induced nephrotoxicity in rats. MATERIALS
      AND METHODS: The rats were randomly divided into five groups of six animals each:
      control, GM (100 mg/kg/day), ATO (10 mg/kg/day), GM + ATO, and GM + Vehicle.
      Kidney function tests, tissue oxidative stress parameters, and histopathological
      and immunohistochemical studies clarified GM nephrotoxicity. RESULTS: GM caused a
      marked reduction in renal functions and increased oxidative stress parameters.
      Histopathological examination revealed tubular necrosis especially in the renal
      cortex in GM rats. On immunohistochemical evaluation, GM rat showed more intense
      expressions of mitogen-activated protein kinase (MAPK), nuclear factor kappa B
      (NF-kappaB), and inducible nitric oxide synthase (iNOS) compared with control.
      Kidney function tests and tissue oxidative stress parameters were normalized in
      the GM + ATO group. Histopathological and immunohistochemical pictures were also
      greatly ameliorated. CONCLUSIONS: ATO acts in the kidney as a potent scavenger of
      free radicals to prevent the toxic effects of GM via the inhibition of MAPK and
      NF-kappaB signaling pathways and iNOS expression.

PMID- 19839840
TI  - 3-aminobenzamide, a poly ADP ribose polymerase inhibitor, attenuates renal
      ischemia/reperfusion injury.
AB  - INTRODUCTION: This study was designed to investigate whether 3-amino benzamide (3
      AB), a poly (ADP-ribose) polymerase (PARP) inhibitor, has a protective effect on
      kidney injury induced by renal ischemia/reperfusion (I/R) by decreasing oxidative
      and nitrosative stress on renal dysfunction and injury. MATERIALS AND METHODS:
      Thirty-two male Sprague-Dawley rats were divided into four groups: sham-operated,
      sham-operated + 3-AB, I/R, I/R + 3-AB. Rats were given 3-AB (100 mg/kg/day ip) 14
      days prior to I/R. I/R and I/R + 3-AB groups underwent 60 min of bilateral renal
      ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood
      were obtained for evaluation. Superoxide dismutase, glutathione peroxidase,
      malondialdehide, protein carbonyl content, and nitrite/nitrate level (NO(x)) were
      determined in the renal tissue. Serum creatinine (S(Cr)), blood urea nitrogen
      (BUN), and aspartate aminotransferase (AST) were determined in the blood.
      Additionally, renal sections were used for histological grade of renal injury.
      RESULTS: 3-AB significantly reduced the I/R-induced increases in S(Cr), BUN, and
      AST. In addition, 3-AB markedly reduced elevated oxidative stress product,
      restored decreased antioxidant enzymes, and attenuated histological alterations.
      Moreover, 3-AB attenuated the tissue NO(x) levels, indicating reduced NO
      production. CONCLUSIONS: 3-AB has beneficial effect on renal glomerular and
      tubular dysfunction in rats' kidneys subjected to I/R injury. Moreover, 3-AB has
      ameliorating effect on both oxidative stress and nitrosative stress of the
      kidneys, which correlated with histopathological evaluation.

PMID- 19839841
TI  - Effects of vitamin D3 (cholecalciferol) on adriamycin-induced nephrotoxicity.
AB  - Although immune-mediated pathogenesis in adriamycin (ADR)-induced nephropathy has
      been proposed recently, studies are lacking about the effects of immunmodulators,
      such as vitamin D, on ADR-induced nephrotoxicity. We hypothesized that vitamin
      D(3) (cholecalciferol) would be beneficial on ADR-induced nephropathy because of
      its immunmodulatory properties. Eighteen male Wistar rats were divided into three
      groups (n = 6): group 1 (control), group 2 (single ADR injection intravenously),
      and group 3 (similar single ADR injection intravenously + daily oral
      cholecalciferol for 21 days) were used in the study. A single high dose of ADR
      resulted in increased urinary protein: creatinine ratio for all three weeks of
      the experiment in both groups 2 and 3 compared with the controls. Histological
      examination of the kidney tissue revealed distinct tubular lesions as tubular
      necrosis, hyaline casts in tubular lumen, tubular degeneration, tubular
      dilatation, and tubular vacuolization in group 2 compared with group 1. These
      tubular lesions were significantly reduced in group 3 compared to group 2. The
      results of this study indicate that cholecalciferol causes satisfactory
      tubulointerstitial recovery in ADR-induced nephrotoxicity in rats.

PMID- 19839842
TI  - Acute renal infarction: an unusual cause of abdominal pain.
AB  - Acute renal infarction is an uncommon and under-diagnosed disease. Its clinical
      presentation is nonspecific and often mimics other more common disease entities.
      The diagnosis is usually missed or delayed, which frequently results in
      irreversible renal parenchyma damage. High index of suspicion is required for
      early diagnosis, as timely intervention may prevent loss of kidney function. We
      report a case of acute renal infarction following coronary angiography in a
      patient with paroxysmal atrial fibrillation who initially presented with acute
      abdominal pain mimicking appendicitis.

PMID- 19839843
TI  - Fifty years of Balkan endemic nephropathy: challenges of study using
      epidemiological method.
AB  - Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease
      associated with urothelial cancer, which affects people living in the alluvial
      plains along the tributaries of the Danube River. Challenges of studying BEN
      using the epidemiological method are multiple. The natural history from exposure
      to occurrence of the disease may take many years. The early stages of BEN are not
      easily detectable clinically, as the disease is asymptomatic until a significant
      decline in function occurs, and even then symptoms are usually non-specific. The
      natural history of BEN is complex, possibly with multiple risk factors operating
      both at the stage of initiation of renal damage and in its progression. In BEN,
      genetic susceptibility is due to multiple genes of small effects, gene-gene
      interactions, and gene-environment interactions of complex nature that are
      difficult to assess with current study designs. BEN is now kidney disease of the
      old people, and many risk factors for disease such as smoking, alcohol
      consumption, obesity, and diabetes could contribute to the kidney damage.
      Evidence is presented that environmental rather than genetic factors play a
      decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a
      culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods.
      Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found
      in the vicinity of endemic settlements, deserve further investigation. Despite
      advances in understanding the epidemiology of BEN, more research is needed on the
      patterns of BEN over time and between places, and on identifying the
      contributions of modifiable risk factors in initiating and hastening progression
      of BEN in order to improve the scope for preventing BEN. Primary prevention is
      still at the beginning. Knowledge accumulated in the fifty years of BEN research
      and new data about prevention and treatment of chronic kidney disease reveal
      several effective methods in secondary and tertiary prevention of BEN. Genetic
      epidemiology could establish the relative size of the genetic effect in relation
      to other sources of variation in disease risk (i.e., environmental effects such
      as intrauterine environment, physical and chemical effects, as well as behavioral
      and social aspects). Public health authorities in the several countries having
      aristolochic acid nephropathy should take immediate measures for reducing dietary
      exposure of residents to Aristolochia.

PMID- 19839844
TI  - Transient hemolytic anemia after kidney transplantation and thrombotic
      thrombocytopenic purpura refractory to plasma exchange and rituximab.

PMID- 19839845
TI  - Geometric analysis of melamine crystal: a problematic molecule inducing renal
      failure in melamine intoxication.
AB  - In 2007, there was emerging toxic nephropathy due to melamine. Renal failure due
      to melamine crystal is noted in cases of melamine intoxication. In this article,
      the author studies the melamine crystal by the molecular docking technique and
      found that the size of crystal is a possible explanation for why the infantile
      population is more prone to develop renal failure after intoxication.

PMID- 19839846
TI  - Highly successful and low-cost desensitization regime for sensitized living donor
      renal transplant recipients.
AB  - 10-30% of dialysis population awaiting renal transplantation is sensitized.
      Present desensitization protocols use intravenous immune globulins, rituximab,
      and plasmapheresis in various combinations; however, these regimens are
      unaffordable by many in developing countries. We tried desensitization with
      mycophenolate mofetil and plasmapheresis. Methods. Patients with high PRA titre
      (> or =50%) or positive crossmatch (>10%) were treated with MMF for a month
      before proposed transplant and were given five sittings of plasmapheresis.
      Results. 11 of 12 patients had normalization of PRA/crossmatch with this regimen
      and were successfully transplanted. One patient lost the graft due to graft vein
      thrombosis, and two patients died within three months after transplant due to
      septicemia and pulmonary embolism, respectively, with a functioning graft. No
      patient, including the two who died, developed clinical rejection over a mean
      follow-up of 10 months (range 1-16 months). Mean serum creatinine at last follow
      up was 1.1 mg/dL (range 0.9-1.3 mg/dL). Conclusions. Though the number of
      patients studied is small, we feel that highly sensitized patients awaiting
      living donor renal transplant should be tried on this simple and cost-effective
      regime before transplant. The more aggressive and expensive approaches
      incorporating IVIg and rituximab should be used only if this relatively low-cost
      regime is unsuccessful.

PMID- 19839847
TI  - A mildly altered vascular homeostasis in early stage of CKD.
AB  - BACKGROUND: A continuous increase in number of CKD patients entering ESRD is a
      growing public health threat, which reflects the present therapeutic failure
      usually initiating at the late stage of CKD. OBJECTIVE: To study the mechanism of
      vascular repair in CKD patients associated with mildly impaired renal function,
      which included angiogenic factors such as VEFG, angiopoietin-1, and flt-1
      (VEGFR1); and antiangiogenic factors such as angiopoietin-2 and KDR (VEGFR2).
      RESULTS: A mild defect in angiogenic factor-namely, angiopoietin-1-was observed,
      whereas VEGF and flt-1 (VEGFR1) were within normal limit. Also, antiangiogenic
      factor-namely, angiopoietin-2-was mildly elevated, whereas KDR (VEGFR2) remained
      within normal limit. CONCLUSION: The mechanism of vascular repair appears to be
      adequately functional in the early stage of CKD. Therapeutic intervention at this
      stage can improve renal perfusion and restore renal function as indicated in
      normoalbuminuric, type 2 diabetic nephropathy. The authors encourage changing the
      conceptual view of treatment under common treatment at late stage of CKD to
      treatment at early stage of CKD under an environment favorable for renal
      regeneration.

PMID- 19839848
TI  - Hyporesponsiveness to erythropoietin therapy in hemodialyzed patients: potential
      role of prohepcidin, hepcidin, and inflammation.
AB  - Hepcidin is the key regulator of iron metabolism. Iron supplementation is often
      introduced in dialyzed patients to replete or to maintain iron stores,
      particularly in patients treated with erythropoietic-stimulating agents. The
      present study was aimed to assess possible relation between hepcidin and
      erythropoietin therapy, with particular attention being paid to erythropoietin
      hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were
      studied using commercially available kits from DRG Instruments GmbH, Germany
      (ELISA method) and Bachem, UK (RIA method). TNFalpha and IL-6 were studied using
      kits from and R&D (Abington, UK), and hsCRP was studied using kits from American
      Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had
      significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and
      residual renal function, and significantly higher serum ferritin, hsCRP, IL-6,
      TNFalpha, and erythropoietin dose. The difference in serum prohepcidin and
      hepcidin did not reach statistical significance; however, there was a tendency
      toward higher values of both prohepcidin and hepcidin in hyporesponsive patients.
      In conclusion, though hyporesponsiveness to erythropoietin therapy occur in
      dialyzed patients, it is mainly associated with subclinical inflammation than
      with hepcidin excess. Further studies are needed to develop a reliable and
      reproducible assay to elucidate the potential contribution of hepcidin to
      hyporesponsiveness during erythropoietin therapy.

PMID- 19839849
TI  - Inflammation and overweight in peritoneal dialysis: is there an association?
AB  - More than 30% of the patients on peritoneal dialysis show chronic systemic
      inflammatory activity with high levels of C-reactive protein. The purpose of this
      cross-sectional study was to investigate the influence of the inflammatory state
      on clinical and nutritional markers in patients on peritoneal dialysis. Twenty
      seven patients were included: mean age was 57.6 +/- 19 years, 48% were male, and
      median time on peritoneal dialysis was 16.0 (8.3; 35.8) months. Clinical,
      dialytic, laboratory, anthropometric and electric bioimpedance data were
      collected with the sample stratified for C-reactive protein. In patients, the
      levels of Interleukin-6 and tumor necrosis factor-alpha were higher, while
      adiponectin levels were lower than in healthy individuals (p < or = 0.001),
      indicating the presence of inflammatory activity in the sample. When compared to
      patients with C-reactive protein <1 mg/dL, those with > or =1mg/dL showed higher
      body mass index (29.4 +/- 6.1 vs. 24.4 +/- 4.5 kg/m(2); p = 0.009), percent of
      standard body weight (124.5 +/- 25.4 vs. 106.8 +/- 17.9 %; p = 0.012), and
      percent of body fat as assessed by both anthropometry (31.3 +/- 9.9 vs. 23.9 +/-
      9.1%; p = 0.056) and bioimpedance (38.9 +/- 6.3 vs. 26.2 +/- 12.6 %; p < 0.001).
      Patients with C-reactive protein > or =1mg/dL also exhibited higher levels of
      ferritin (701 +/- 568 vs. 532 +/- 356 ng/mL; p =0.054) and lower total lymphocyte
      count (median 1838 vs. 1638 mm3; p = 0.001). In conclusion, higher body mass
      index and body fat markers were associated with C-reactive protein > or = 1mg/dL,
      and higher C-reactive protein was associated with immunocompetence impairment
      evidenced by the lower total lymphocyte count. Our findings confirm the
      relationship between inflammation, body fat, and immunocompetence, which may be
      superimposed potentializing the inflammatory status.

PMID- 19839850
TI  - Long-term online hemodiafiltration does not reduce the frequency and severity of
      acquired cystic kidney disease in hemodialysis patients.
AB  - BACKGROUND: Acquired cystic kidney disease (ACKD) is a frequent complication in
      chronic hemodialysis (HD) patients and a risk factor for renal cell carcinoma.
      Online hemodiafiltration (HDF) provides better clearance of middle molecular
      weight solutes, but its effect on ACKD has not been investigated. MATERIALS AND
      METHODS: This case-control study enrolled 86 patients (43 HDF patients and 43 HD
      patients) who were matched according to age, sex, and duration of renal
      replacement therapy. The mean duration of HDF was 63 (+/- 35) months. The
      frequency and severity of ACKD was evaluated by ultrasonography using a severity
      scoring system. RESULTS: We observed ACKD in 23 of the HD patients (53.5%) and 21
      of the HDF patients (48.8%). This difference was not statistically significant (p
      = 0.829). The overall ACKD severity scores were similar in the two groups (p =
      0.875). Patients on HDF had significantly lower serum levels of alkaline
      phosphatase and intact parathyroid hormone. Multiple logistic regression analysis
      indicated that duration of renal replacement therapy was the only risk factor for
      the presence of ACKD (p < 0.001). There was a significant correlation between
      duration of renal replacement therapy and ACKD severity score (r = 0.589, p <
      0.001). CONCLUSIONS: Our results suggest that long-term online HDF does not
      reduce the frequency and severity of ACKD in dialysis patients. Duration of renal
      replacement therapy is the most important risk factor for ACKD. Factors that
      cannot be corrected by use of HDF may contribute to the formation of renal cysts.

PMID- 19839851
TI  - Determination of ghrelin immunoreactivity in kidney tissues of diabetic rats.
AB  - BACKGROUNDS/AIMS: Ghrelin, a recently discovered hormone, is released largely
      from stomach and might affect insulin secretion and glucose metabolism. The aim
      of this study was to determine the immunohistochemical localization of ghrelin in
      streptozotocin-induced diabetic rat kidneys. METHODS: Fifty-four adult male
      Wistar rats were used in this study. All rats were divided into nine groups
      according to three time points of the study (2, 4, and 6 weeks) as control group,
      control group given 0.1 M phosphate-citrate, and diabetic group given 50 mg/kg
      streptozotocin intraperitoneally. The rats in all groups were decapitated at the
      end of 2, 4, and 6 weeks of the study. The kidneys of the rats were removed, and
      tissue samples were processed by using routine paraffin techniques. The samples
      were immunohistochemically stained using avidin-biotin-peroxidase method for
      ghrelin immunoreactivity. RESULTS: There were no differences of ghrelin
      immunoreactivity between the control groups. Ghrelin immunoreactivity was
      observed in both distal tubulus and collecting ducts in the diabetic groups,
      while it was detected only in distal tubules of the control groups. The intensity
      of ghrelin immunoreactivity was increased at 4 and 6 weeks of the study in the
      diabetic groups. CONCLUSION: Increased ghrelin immunoreactivity in the diabetic
      rat kidney tissues suggests that ghrelin may contribute to the pathophysiological
      mechanism of diabetic nephropathy.

PMID- 19839852
TI  - The effects of low-dose erythropoiesis-stimulating agents on peritoneal fibrosis
      induced by chemical peritonitis and on peritoneal tissue MMP-2 and TIMP-2 Levels
      in rats.
AB  - AIM: The objective of the present study was to investigate the effect of low-dose
      erytropoesis-stimulating agents (ESA) on the development of peritoneal fibrosis
      in chlorhexidine gluconate-induced peritoneal sclerosing rats and to assess the
      peritoneal tissue levels of MMP-2 and TIMP-2, which may be regarded as factors in
      the development of peritoneal fibrosis. SUBJECTS AND METHODS: Twenty-four Wistar
      albino rats were divided into three groups. The control group received 0.9%
      saline (3 ml/d) intraperitoneally, the CH group received 3 ml daily injections of
      0.1% chlorhexidine gluconate (CH) intraperitoneally, and the CH+ESA group
      received 3 ml daily injections of 0.1% CH intraperitoneally and epoetin beta (3 x
      20 IU/kg/week) subcutaneously. On the twenth-first day, rats were sacrificed, and
      parietal peritoneum samples were obtained from the left anterior abdominal wall.
      Pathological samples were examined using Hematoxyline & Eosin (HE) stains. The
      thickness, vascular proliferation, and inflammation were determined by light
      microscopy. MMP-2 and TIMP-2 were studied immunohistochemically by monoclonal
      antibody staining. RESULTS: Inflammation, vascular proliferation, and fibrotic
      area percentages were not statistically significant between groups.
      Histopathologically control, CH, CH+ESA groups peritoneal thickness were 8.02 +/-
      2.89, 146.74 +/- 26.1, and 48.12 +/- 16.8 micrometers, respectively. The decrease
      in thickness of parietal peritoneum in CH+ESA group was statistically significant
      when compared to CH. Immunohistochemically, interferon was shown to decrease MMP
      2 expression on parietal peritoneum than group CH, but has no effect on TIMP-2.
      DISCUSSION: Low-dose ESA histopatologically reduces peritoneal fibrosis induced
      by chlorhexidine gluconate. However, from dosage and duration points of view, we
      need extended clinical and experimental studies.

PMID- 19839853
TI  - Does haloperidol have side effects on histological and stereological structure of
      the rat kidneys?
AB  - Haloperidol, a typical antipsychotic, is the most commonly prescribed medication
      for the treatment of mental health problems such as agitation and psychosis. We
      attempted to determine the effects of haloperidol treatment on the kidneys of
      female rats. In addition, we aimed to estimate the numerical density, total
      number, and height of renal glomeruli and the volume and volumetric fractions of
      the cortex, medulla, and whole kidneys, and tried to determine whether there was
      a change in these stereological parameters depending on haloperidol treatment.
      Both the qualitative and quantitative histological features of the kidney samples
      were analyzed with conventional histopathological and modern stereological
      methods at the light microscopic level. The total number of glomeruli and
      numerical density of glomerulus in the haloperidol-treated groups was not changed
      by increasing the dose in comparison to the control group. The mean height of the
      glomerulus significantly increased, especially in low-dose groups. In the
      haloperidol-treated groups, the volumetric fractions of the cortex to the whole
      kidney of the rats were significantly decreased by increasing the dose. The
      volumetric fractions of the medulla to the whole kidney of the rats were
      increased significantly in parallel by the given dose. In addition, we present
      quantitative findings showing that haloperidol is associated with many
      alterations in rat kidneys. It was shown that haloperidol may lead to undesirable
      changes in the kidney after chronic treatment with especially high doses.

PMID- 19839854
TI  - Epstein syndrome presenting as renal failure in young patients.
AB  - Two young Chinese patients presented with renal failure and thrombocytopenia.
      Further investigations showed the presence of large platelets and high-frequency
      sensorineural hearing deficit. Genetic studies confirmed mutations in the gene
      encoding the myosin heavy chain (MYH-9), and Epstein Syndrome was diagnosed. One
      patient underwent deceased-donor kidney transplantation with satisfactory graft
      function. Epstein Syndrome is a rare genetic disorder with autosomal dominant
      inheritance. Clinicians should be aware of this entity when a young patient
      presents with renal failure and thrombocytopenia.

PMID- 19839855
TI  - Renal consequences of long-term, low-dose intentional ingestion of ethylene
      glycol.
AB  - Acute renal failure can result from a wide variety of causes. When the cause of
      acute renal failure is unclear, the history, physical examination, and laboratory
      findings are crucial to help establish the cause. However, the cause of acute
      renal failure may remain unclear even after gathering this information. In this
      report, we describe a case of acute chronic renal failure in which the cause of
      acute renal failure was not determined until a kidney biopsy was performed, which
      revealed calcium oxalate crystals in the renal parenchyma, a finding
      pathognomonic for ethylene glycol ingestion.

PMID- 19839856
TI  - Urofacial (ochoa) syndrome: can a facial gestalt represent severe voiding
      dysfunction?
AB  - Urofacial (Ochoa) syndrome is a rare autosomal-recessive disorder that features
      an unusual "inverted" facial expression, such that patients appear to be crying
      when they smile. This syndrome also involves serious urinary tract disorders,
      though the diagnosis may be missed because of variability of these problems and
      failure to recognize the characteristic facial grimacing. The urinary issues
      usually result in enuresis, urinary tract infection, and hydronephrosis, and some
      severely affected patients become hypertensive and progress to end-stage renal
      disease. Early diagnosis is very important for management of urinary problems and
      best prognosis in these patients. We report the first published case of urofacial
      syndrome in Turkey. The patient was diagnosed at 16 years of age, after having
      been followed with the diagnosis of recurrent urinary tract infection and vesico
      ureteral reflux. Physicians should keep this syndrome in mind for any patient who
      presents with dysfunctional voiding, particularly in countries with high rates of
      consanguineous marriage.

PMID- 19839857
TI  - Aortoiliac intervention with distal protection to salvage a heterotopic renal
      transplant.
AB  - A case of substantial debris captured by an embolic protection device placed in a
      patient's transplanted renal artery during common iliac artery angioplasty and
      stent placement is presented. To the authors knowledge, no previous literature
      exists pertaining to renal artery protection in patients with a history of a
      heterotopic renal transplant undergoing aortoiliac endovascular interventions.

PMID- 19839858
TI  - Emphysematous pyelonephritis: a case report series of four patients with review
      of literature.
AB  - Emphysematous pyelonephritis (EPN) is an acute necrotizing infection with gas
      presence in the kidney, perinephric space, and/or urinary collecting system that
      carries a bad prognosis. Some clinical conditions predispose to this entity, such
      as diabetes mellitus, urinary tract obstruction, and immune-incompetence.
      Immediate resuscitation, broad-spectrum antibiotics, percutaneous and surgical
      drainage, and emergent and delayed nephrectomy are therapeutic options that
      should be applied in a timely fashion. We report our experience of four patients
      with EPN. Two of the patients were kidney transplant recipients, one patient had
      bilateral urolithiasis, and one patient was an elderly patient with debilitated
      general condition and an abdominal mass that could not be defined. Late
      transplant nephrectomy was performed in one patient, and three patients were
      treated conservatively. Three patients died, including the patient who had
      transplant nephrectomy. One patient who presented with lithiasis showed a
      remarkable recovery with conservative management. The bacteria involved were E.
      Coli and a resistant Klebsiella. We conclude that EPN is a life-threatening
      condition that carries a bad prognosis. Early diagnosis is essential for a
      positive outcome. Therapeutic measures should be applied immediately after
      diagnosis. An aggressive approach including nephrectomy may be emergently
      required.

PMID- 19839860
TI  - Reversible renal failure due to bilateral renal sarcoma in a patient with acute
      myeloid leukemia.
AB  - A 68-year-old male presented with acute myeloid leukemia, renal failure,
      hypokalemia, and enlarged kidneys on renal ultrasound. Renal biopsy revealed
      massive leukemic infiltration of the kidney. After systemic chemotherapy, the
      patient developed tumor lysis syndrome followed by a phase of proximal tubule
      dysfunction presenting as polyuria and diverse electrolyte abnormalities. In
      time, renal function returned to normal, as did kidney size. This report shows
      that renal failure, enlargement of the kidneys, and tubule dysfunction in the
      course of AML infiltrating the kidneys can be reversed by treatment of the
      hematological disease.

PMID- 19839859
TI  - Papillorenal syndrome after Beta-interferon treatment in pregnancy.
AB  - Papillo-Renal Syndrome (PRS, or Renal-Coloboma Syndrome) is an autosomal dominant
      disorder, characterized by colobomatous eye defects, abnormal vascular pattern of
      the optic disk, renal hypoplasia, vesicoureteral reflux, high-frequency hearing
      loss, and sometimes central nervous system (CNS) abnormalities. The syndrome is
      associated with mutations in the PAX2 gene. This 11-year-old girl's mother was
      treated with beta-interferon (IFNbeta-1a) for multiple sclerosis (MS) during the
      pregnancy. The child failed to thrive in infancy and early childhood. The
      multicystic renal dystrophy, hypoplastic right kidney, and vesico-ureteral reflux
      (II-III grade) were diagnosed by ultrasound and radionucleotide renal scan.
      Subsequently, a morning glory anomaly and coloboma of the optic disc was
      discovered. Renal failure progressively followed. MRI of the head revealed a cyst
      of the right optic nerve. Genetic analysis revealed a mutation of the PAX2 gene
      (619 insG). The multicystic renal dystrophy and a cyst of the optic nerve in
      association with PRS syndrome have only rarely been described. The fact that this
      PRS patient stemmed from a pregnancy under beta-interferon treatment raises the
      question whether IFNbeta-1a treatment during pregnancy has influenced the
      manifestation or the severity of the PAX2 mutant phenotype in this child.

PMID- 19839861
TI  - Hepatitis C infection and related factors in hemodialysis patients in china:
      systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: To provide a comprehensive and reliable tabulation of
      available data on the epidemiological characteristics and risk factors for
      hepatitis C virus (HCV) infection in maintenance hemodialysis (HD) patients in
      China, and to help inform prevention programs and guide future research. METHODS:
      A systematic review was constructed based on the computerized literature database
      by two reviewers independently. Ninety-five percent confidence intervals (CI) of
      infection rates were calculated using the approximate normal distribution model.
      Odds ratios and 95% CI were calculated by fixed or random effects models.
      RESULTS: Forty-three studies met our inclusion criteria. The pooled prevalence of
      HCV infection among HD patients in China was 41.1% (95% CI 39.5-42.6%). No
      significant difference was found in HCV infection rates between male and female
      HD patients (OR = 0.75, 95% CI 0.52-1.07, p = 0.11). HD patients with blood
      transfusion were 5.65 times more likely to be infected with HCV than HD patients
      without blood transfusion. A longer duration of HD was associated with increased
      HCV prevalence. Co-infection with hepatitis B virus did not increase the
      probability of HCV infection among HD patients (OR = 1.19, 95% CI 0.34-3.20, p =
      0.73). CONCLUSIONS: Viral hepatitis is still one of the main complications in HD
      patients, with hepatitis C being the most common one. The key to reducing the
      incidence of viral hepatitis in HD patients is to control contagion and reduce
      the frequency of blood transfusion and cross-infection.

PMID- 19839862
TI  - Prevalence rate of acute renal failure in HELLP syndrome: a summary from a single
      country's data.

PMID- 19839863
TI  - NGAL: a new missing link between inflammation and uremic anemia?

PMID- 19839864
TI  - Effect of pseudophakia on standard perimetry parameters.
AB  - PURPOSE: To investigate the effect of monofocal spheric acrylic intraocular
      lenses (IOL) on the visual field (VF) parameters. MATERIALS AND METHODS: Thirty
      six healthy pseudophakics (group 1) and 42 age-matched healthy volunteers (group
      2) who had visual acuity of > or = 9/10 Snellen lines underwent central 24-2
      threshold VF testing by Humphrey 750i VF analyzer. Subjects of group 1 had
      undergone VF testing 2 months after cataract surgery. The VFs were divided into
      three concentric zones for analysis. Age, visual acuity, pupillary size, foveal
      threshold, mean (MD) and pattern standard deviation (PSD) values, and mean
      decibel (dB) thresholds. MD and PSD of the three concentric zones were compared
      between the groups. RESULTS: There was no significant difference between the
      groups in regards to age, gender, pupillary size, visual acuity, and mean foveal
      threshold. Mean MD was -2.4 +/- 2.5 decibel (dB) in the pseudophakics and -1.06
      +/- 1.9 dB in the controls (p = 0.01; t = -2.63). Mean PSD values of group 1 and
      2 were 2.5 +/- 1.5 dB and 2.06 +/- 1.3 dB, respectively (p = 0.145; t = -1.47).
      There were statistically significant differences between mean MD values of three
      concentric zones of both groups (p < 0.003, for all). The reduction of VF
      sensitivity through peripheral retina was more pronounced in the pseudophakics.
      CONCLUSION: Even monofocal spheric acrylic IOLs have relatively insignificant
      effect on visual acuity, and foveal threshold may influence global indices such
      as MD on VF testing. Possible causes of reduction in VF sensitivity should be
      clarified by further studies in pseudophakics.

PMID- 19839865
TI  - A vitreous hemorrhage animal model in rabbits using force percussion injury.
AB  - PURPOSE: To make a standard vitreous hemorrhage (VH) animal model in rabbits for
      clinical and experimental research using force percussion injury (FPI). METHODS:
      Ten New Zealand white adult rabbits age 3 to 4 months with a body weight between
      2 and 2.5 kg without any ocular disorders were given bilateral blunt trauma to
      the eyes with FPI. Two adult rabbits without any ocular disorders were in the
      control group without any trauma. All traumatic eyes were examined with slit
      lamp, indirect ophthalmoscope, B-scan, and pathology. Slit lamp photographs and
      ocular fundus photographs were also taken. All these examinations were performed
      1, 3, 7, 14, 30, and 60 days after the ocular trauma. We checked for the presence
      or absence of VH in all traumatic eyes. Retinal detachment was assessed by B
      scan. RESULTS: All 20 eyes in the experimental group had post-traumatic VH after
      ocular injury (success ratio 100%). Seventeen of 20 eyes (85%) were good models
      (GM) and developed severe VH. VH began to decrease one week after the ocular
      trauma and then was gradually absorbed and disappeared within two months after
      the ocular trauma. Three eyes (15%) had a little blood in the anterior chamber.
      Six eyes (30%) had some exudates in the anterior chamber. Only one eye (5%) had a
      slight traumatic cataract within one week (5-7 days) and kept stable. Lens
      displacement was also found in three eyes (15%). No retinal detachment or
      choroidal hemorrhage were found in any traumatic eyes. Both groups were followed
      up for two months. Rabbits in the control group were normal and were without VH.
      CONCLUSION: A reproducible experimental model of VH in rabbit eye has been
      successfully made. Massive VH was demonstrated on clinical observations and
      echography and was confirmed by histopathological examinations. VH was totally
      absorbed two months after the ocular trauma in our model. Our model is a simple,
      reliable, reproducible, and stable tool for the research on the mechanism and
      treatment of VH.

PMID- 19839866
TI  - Role of IL-1beta on the glutamine synthetase in retinal Muller cells under high
      glucose conditions.
AB  - PURPOSE: To investigate (1) the role of cytokine interleukin-1beta on the
      glutamine synthetase in retinal Muller cells under high glucose condition, (2)
      the mechanism for down-regulation of glutamine synthetase in retinal Muller cells
      induced by interleukin-1beta under high glucose conditions. MATERIALS AND
      METHODS: The effect of interleukin-1beta on the expression of glutamine
      synthetase and c-Jun in retinal Muller cells under normal and high glucose
      conditions was measured by immunocytochemistry, Western blot, and real-time (RT)
      PCR, and was further confirmed by c-Jun siRNA method. RESULTS: Under high glucose
      conditions, interleukin-1beta significantly increased expression of c-Jun and
      decreased the expression of glutamine synthetase. When c-Jun gene was silenced by
      siRNA, interleukin-1beta could not decrease glutamine synthetase expression in
      high glucose concentrations. CONCLUSIONS: Interleukin-1beta decreases expression
      of glutamine synthetase via activation of c-Jun. The data suggested that
      interleukin-1beta may play a role in the development of diabetic retinopathy.

PMID- 19839868
TI  - Potential application of adult stem cells in retinal repair--challenge for
      regenerative medicine.
AB  - Stem cells (SCs) maintain the balance among somatic cell populations in various
      tissues and are responsible for organ regeneration. The remarkable progress of
      regenerative medicine in the last few years indicates promise for the use of SCs
      in ophthalmic disorder treatment. This review describes the current view on
      hierarchy in the SC compartment and presents the latest attempts to use adult SCs
      in the regeneration of the retina. Research performed primarily in animal models
      gives hope for using similar strategies in humans. However, the search for the
      optimal source of SCs for cell therapy continues. We briefly discuss various
      potential sources of adult SCs that could be employed in regenerative medicine,
      particularly focusing on recently identified, very small embryonic-like SCs (VSEL
      SCs). These cells are even present in the bone marrow and adult tissues of older
      patients and could be harvested from cord blood. We believe that VSEL-SCs, after
      the establishment of ex vivo expansion and differentiation protocols, could be
      harnessed for retina regeneration.

PMID- 19839867
TI  - Genotoxic effects of carotenoid breakdown products in human retinal pigment
      epithelial cells.
AB  - PURPOSE: To investigate the genotoxic effects of lutein (LBP) and beta -carotene
      breakdown products (beta -apo-8-carotenal, BA8C) and the preventive role of GSH
      in human retinal pigment epithelial cells (ARPE-19). METHODS: LBP- and BA8C
      induced DNA damage in human retinal pigment epithelial cells (ARPE-19) was
      determined by comet assay. The DNA damage was quantified by the image analysis
      system using Comet Score software. ARPE-19 cell viability was determined by
      CellTiter 96 AQ(ueous) one-solution cell proliferation assay kit. Intracellular
      GSH levels were measured by Ellman's reagent. RESULTS: Incubation of serum
      starved ARPE-19 cells with LBP and BA8C caused significant DNA damage in a dose-
      and time-dependent manner. The DNA damage and cell death incurred by LBP and BA8C
      were significantly prevented by N-acetylcysteine (NAC) but not by alpha 
      tocopherol + ascorbic acid (T + AA). Furthermore, BSO-induced GSH depletion in
      ARPE-19 cells caused a significant elevation in LBP- and BA8C-induced DNA damage,
      whereas increased GSH levels in ARPE-19 cells prevented it. CONCLUSIONS: Our
      results suggest that breakdown products of dietary carotenoids could be genotoxic
      in ARPE-19 cells. LBP-induced genotoxic effects could worsen oxidative stress.
      The intracellular GSH pool in ARPE-19 cells might play a critical role in
      carotenoid breakdown products-induced genotoxicity.

PMID- 19839870
TI  - Vehicle used for triamcinolone acetonide is toxic to ocular tissues of the
      pigmented rabbit.
AB  - PURPOSE: To investigate the potential toxicity of the vehicle used for
      triamcinolone acetonide (TA) to the cornea, lens, ciliary body, and retina of
      pigmented rabbits. METHODS: Forty chinchilla rabbits (40 eyes) were divided into
      four groups: group A (control group) eyes received an intravitreal injection of
      0.1 ml sterile saline solution; group B eyes received 0.1 ml (1.3 mg) TA plus
      vehicle; group C eyes received 0.1 ml (1.3 mg) TA alone (vehicle eliminated);
      group D eyes received 0.1 ml vehicle only. Intraocular pressure (IOP) was
      measured pre-injection and at 1, 7, 14, 30, and 90 days post-injection. Scotopic
      and photopic electroretinograms (ERG) were examined pre-injection and 7, 30, and
      90 days post-injection. Animals were sacrificed 7, 30, and 90 days post
      injection. Eyes were enucleated and examined by light microscopy (LM) and
      electron microscopy (EM). RESULTS: The IOP of groups B and C was higher than that
      of other groups on days 1, 7, and 14 post-injection (p < 0.05). ERG amplitudes of
      groups B and D were lower than those of other groups on days 7 and 30 post
      injection (p < 0.05). Histopathological sections indicated morphologic changes in
      the ciliary body, lens, and retina of eyes in groups B and D. CONCLUSIONS:
      Vehicle used for TA is toxic to the lens, ciliary body, and retina of pigmented
      rabbit eyes after injection of intravitreal TA.

PMID- 19839869
TI  - Role of extracellular phospholipase B of Candida albicans as a virulent factor in
      experimental keratomycosis.
AB  - PURPOSE: To determine the virulence of extracellular phospholipase B (PLB) of
      Candida albicans in keratomycosis. METHODS: A model of keratomycosis was
      established in 48 New Zealand albino rabbits covered with contact lenses. Effects
      of PLB-deficient mutant strain of C. albicans and its isogenic parental strain on
      the keratomycosis were compared. In vitro, these two strains were incubated with
      corneal stromal cells respectively (37 degrees C, 5% CO(2)). The influence of the
      strains on monolayer keratocytes was detected by scanning electron microscopy,
      enzyme-linked immunosorbent assay, and flow cytometry with Annexin-V/propidium
      iodide. RESULTS: Fungal hyphae grew perpendicularly to the corneal stromal
      lamellae. The difference of the two strains in hyphal invasion was significant at
      two days after inoculation (p = 0.002) but not significant at the other
      timepoints. Severity of inflammation in rabbits with the parental strain was the
      same as that with the PLB null strain (p > 0.05). The morphogenesis and number of
      adherent germ tubes of the two strains were similar (p > 0.05), but the number of
      germ tubes penetrating cell monolayer was significantly different (p = 0.009).
      More prostaglandin E(2) was detected in the culture supernatants of the parental
      strain group than the null strain group. The percentages of cells with damaged
      cellular membrane were 3.02%, 2.04%, and 0.12% in the parental group, the PLB
      null group, and the control group, respectively. Apoptosis cells accounted for
      33.17%, 27.56%, and 1.46%, and living cells accounted for 63.81%, 70.40%, and
      98.41% in the three groups, respectively. CONCLUSION: PLB can play a role as a
      virulent factor in triggering fungal invasion in corneas immediately after fungal
      adherence by decomposing membrane phospholipids and leading to cell lysis.
      However, its virulent effect does not appear to be as critical as in the
      hematogenous model of disseminated candidiasis.

PMID- 19839871
TI  - Hydrocortisone suppression of the expression of VEGF may relate to toll-like
      receptor (TLR) 2 and 4.
AB  - PURPOSE: The purpose of this study was to investigate hydrocortisone's potential
      in inhibiting the expression of VEGF in cultured human cornea fibroblasts (HCF)
      and to determine whether the role of hydrocortisone in the expression of VEGF may
      relate to toll-like receptors 2 and 4 (TLR2 and TLR4). METHODS: Three different
      concentrations of hydrocortisone were used to stimulate the cultured HCF. The
      cellular abundance of the mRNAs for VEGF and TLR2, 4 were determined by real-time
      polymerase chain reaction analysis. The release of IL-6, IL-8, and VEGF from
      cultured HCF was measured using enzyme-linked immunosorbent assays (ELISA) in the
      presence and absence of specific blocking antibodies to TLR2, 4. The proteins of
      TLR2, 4 were also compared by Western blot. RESULTS: Following incubation of HCF
      with hydrocortisone, we found the mRNA expression of TLR2, 4 and VEGF were
      markedly inhibited. ELISA and Western blot analysis confirmed that protein
      expression of TLR2, 4 and VEGF was down-regulated in response to hydrocortisone.
      The result of ELISA also showed the release of IL-6 and IL-8 can be inhibited by
      hydrocortisone. But all these inhibitions were partly counteracted after
      pretreatment with anti-TLR2 and/or anti-TLR4 monoclonal antibody. CONCLUSIONS:
      Hydrocortisone may decrease the expression of VEGF through inhibiting TLR2, 4
      activity in cultured human corneal fibroblasts.

PMID- 19839872
TI  - Toxic effect of methamphetamine on the retina of CD1 mice.
AB  - PURPOSE: To investigate whether systemic administration of methamphetamine (METH)
      induces retinal damage in CD1 mice. MATERIALS AND METHODS: Eighteen male CD1 mice
      were randomly assigned to three groups, six mice per group: Group 1 receiving a
      single dose of 40 mg/kg METH, Group 2 receiving four doses of 10 mg/kg METH, and
      Group 3 (control) receiving 40 mg/kg 0.9% NaCl solution. METH and NaCl were
      administered by intraperitoneal injection. Immunostaining of glial fibrillary
      acidic protein (GFAP), S-100 for astrocytes and Muller cells, CD11b for
      microglia, and tyrosine hydroxylase (TH) and TUNEL labeling for apoptotic cell
      death were performed on the retinal sections on day 1 and day 7 post-exposure.
      RESULTS: GFAP and S-100 immunoreactivity was observed in Group 1 mice. CD11b+
      cells in Group 1 mice showed more intensely stained shorter and thicker cellular
      processes than Groups 2 and 3, indicating activated microglia in the mice exposed
      to large-dose METH. No significant difference in TH level was seen among the
      three groups. TUNEL labeling did not reveal positive cells in the retinas of any
      of the 18 CD1 mice. CONCLUSIONS: A single large dose of METH induces an increase
      in short-term protein expression of GFAP and S-100 and in microglial activation.
      The results suggest that METH has a neurotoxic effect on CD1 mouse retina.

PMID- 19839873
TI  - Rescue of photoreceptors by BDNF gene transfer using in vivo electroporation in
      the RCS rat of retinitis pigmentosa.
AB  - PURPOSE: To investigate the feasibility of introducing brain-derived neurotrophic
      factor (BDNF) gene into retinal pigment epithelial cells in vivo by
      electroporation and whether this method can rescue photoreceptors of retinitis
      pigmentosa in Royal College Surgeons (RCS) rats. METHODS: The BDNF-GFP fusion
      eukaryotic-expressing plasmid was constructed and subretinally or intravitreously
      injected into the eyes of RCS rats followed by in vivo electroporation. The
      expression of BDNF mRNA and protein was detected by RT-PCR and Western immunoblot
      analysis. The number of surviving photoreceptors was counted, and the TdT-dUTP
      terminal nick-end labeling (TUNEL) method was used to detect the apoptotic
      retinal cells at different timepoints after introduction of BDNF plasmid.
      RESULTS: Treated eyes showed a significantly higher rescue ratio and a lower
      number of TUNEL-positive photoreceptors than did the control eyes at various
      timepoints. CONCLUSION: These findings provide evidence that electroporation is
      an effective method for gene transfer into retinal pigment epithelial cells, and
      the rescue of photoreceptors can be achieved by BDNF gene transfection with
      electroporation.

PMID- 19839876
TI  - Editorial. Graves' orbitopathy.

PMID- 19839875
TI  - Social participation through the eyes of people with aphasia.
AB  - BACKGROUND: Little is known about the way people with aphasia perceive their
      social participation and its influencing factors. AIMS: To explore how people
      with aphasia perceive participation in society and to investigate influencing
      factors. METHODS & PROCEDURES: In this qualitative study thirteen persons with
      aphasia and twelve central caregivers kept a pre-structured diary over two weeks,
      followed by a semi-structured interview. Diaries and interviews were transcribed
      verbatim and analysed by two researchers independently using codes, categories
      and central themes inductively. Plausibility of the analyses was discussed
      several times with a third independent senior-researcher. In a focus group
      interview, the results were discussed with the participants. OUTCOMES & RESULTS:
      The number of social activities and the character of these activities are not as
      important as the perceived engagement in the social activities for the
      participants. People with aphasia feel isolated but want to feel engaged. They
      feel burdensome to others and wish to function in an ordinary way. Extracting
      information from conversations is difficult but they want to know what is going
      on. Often they are not able to work and they wish to contribute to the community
      in other ways. Although they often feel stigmatized, they wish to be respected.
      Often they do not reach that goal. Perceived factors influencing engagement in
      social participation can be divided into personal, social and environmental
      factors. The following personal factors are reported: motivation, physical and
      psychological condition and communication skills. The social factors are: the
      role of the central caregiver and the characteristics of the communication
      partner(s), namely willingness, skills and knowledge. The environmental factors
      refer to quietness and familiarity of the place in which the person with aphasia
      live. CONCLUSIONS: Social participation is a theoretical concept that people with
      aphasia do not use. Instead, people speak in terms of engagement, involvement,
      having a feeling of belonging. People with aphasia describe the degree of
      engagement in activities in social life domains (i.e. the quality of activities)
      as more important than the quantity of performing activities.

PMID- 19839874
TI  - Impact of the transfer of sFlt-1 gene fragments on the ERK1/2 pathway of VEGF in
      vitro.
AB  - PURPOSE: To investigate whether various sFlt-1 gene fragments affect the
      biological functions and ERK1/2 pathway of vascular endothelial growth factor
      (VEGF) under conditions of hypoxia or in the presence of high glucose
      concentrations in vitro. METHODS: Plasmids expressing loops 2-3 and loops 2-4 of
      sFlt-1 were packed in carboxymethylated dextran-coated nanoparticles and
      transferred into human umbilical vein endothelial cells (HUVECs), which were then
      cultured under hypoxia or in a high-glucose environment. The proliferation and
      migration of HUVECs were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay and low-power microscopy, respectively. Western blot
      analyses were performed to detect p-ERK1/2 protein expression. RESULTS: After
      transfection with the sFlt-1(2-3) or sFlt-1(2-4) gene fragment, the proliferation
      and migration of HUVECs were markedly reduced, and p-ERK1/2 protein expression
      was down-regulated under both hypoxic and high-glucose conditions. The impacts on
      the proliferation, migration of HUVECs, and on p-ERK1/2 protein expression did
      not differ significantly between the sFlt-1(2-3) and sFlt-1(2-4) gene fragments.
      CONCLUSIONS: Both sFlt-1(2-3) and sFlt-1(2-4) gene fragments inhibited the
      proliferation and migration of HUVECs, as well as signal transduction in the
      ERK1/2 pathway of VEGF.

PMID- 19839877
TI  - Non-invasive peri-orbital rejuvenation: radiofrequency dual radiowave energy
      source (RF) and light emission diode system (LED).
AB  - INTRODUCTION: Non-ablative skin rejuvenation is becoming increasingly popular.
      Ellman RF produces an electric current that generates heat in the dermis
      producing a contraction of the collagen. LED is a non heating light emission
      system that induces fibroblast proliferation. MATERIALS AND METHODS: 30 Caucasian
      women, prototype I-IV, age from 35 to 65 with peri-orbital photo damage were
      randomly divided in 3 groups. Group 1 received: 5 RF sessions, 1 every 10 days.
      Group 2 received 8 LED sessions, 1 every 5 days. Group 3 received RF and LED: 1
      RF, 2 LED sessions every 5 days for 3 times (3 RF and 6 LED sessions). A score of
      satisfaction, considering skin texture, rhytidis reduction and firmness was
      obtained before the treatment, after each session and 2 months after the last
      session. RESULTS: Two months after the last treatment in group 1:7 patients were
      satisfied and 3 were very satisfied; in group 2: 6 patients were satisfied and 4
      were very satisfied, in group 3: 4 patients were satisfied and 6 were very
      satisfied. LED was effective on improvement of skin texture and rhytidis
      reduction while slightly effective on firmness. RF was effective on skin texture
      and firmness while slightly effective on rhytidis reduction. LED and RF together
      were effective on all parameters. CONCLUSION: LED and RF seem to be safe and
      effective on skin rejuvenation especially when associated.

PMID- 19839878
TI  - Imaging in Graves' orbitopathy.
AB  - In patients with Graves' orbitopathy, magnetic resonance imaging (MRI) is a
      useful tool to distinguish the acute inflammatory active disease in demonstrating
      interstitial edema within the extraocular muscles on coronal TIRM-sequences from
      fibrotic, inactive endstage disease. MRI is the modality of choice to identify
      active inflammatory changes in order to decide on possible immunomodulatory
      treatment response. However, MRI should be considered in atypical cases as in
      asymmetrical orbital involvement, to exclude other orbital pathologies and to
      confirm the clinical suspicion of apical optic nerve compression in Graves'
      orbitopathy. Computed tomography (CT) provides precise imaging of the osseous
      periorbital structures and does not reveal information on the disease activity in
      most cases. It is therefore the method of choice to plan CT-guided orbital
      decompression surgery in the inactive phase of disease.

PMID- 19839879
TI  - Thyroid eye disease: a historical perspective.
AB  - Within the short period from 1802 to 1840 four physicians from four different
      countries (Flajani in Italy, Parry in England, Graves in Ireland and Basedow in
      Germany) independently described a hitherto unknown disease, the hallmark of
      which were tachycardia and enlargement of the thyroid. Three of the physicians
      also noted exophthalmos. In sequence, the disease was attributed to primary
      cardiac disease, then to increased sympathetic nerve discharge, and finally to
      thyroid hyper-function. The latter concept failed to explain the exophthalmos,
      which cannot be reproduced by over-dosage of thyroid hormone. Explanations for
      the exophthalmos went from cardiac failure (causing swelling of the thyroid and
      retro-orbital tissues), to sympathetic nerve discharge, to over-secretion of TSH,
      to production within the pituitary of TSH fragments with exophthalmogenic
      properties, and finally to shared auto-antigens of thyroidal and retroorbital
      tissue. The latter theory is favoured today, after it had been recognized that
      thyroid hyperfunction in Graves' disease was due to auto-antibodies to the
      thyroidal TSH receptor; such receptors were postulated also to be present in
      retroorbital tissue. Thus, each generation of scientists explained the
      pathogenesis of exophthalmos with the methods and concepts available to medical
      research at any given time. Although big advances have been made, future research
      may be good for some unexpected surprises.

PMID- 19839880
TI  - Small versus coronal incision orbital decompression in Graves' orbitopathy.
AB  - Ideally the planning of decompression surgery should be adequate to the severity
      of the orbitopathy, its possible "lipogenic" or "myopathic" variants, the
      patient's specific orbital osteology and possible previous surgeries. Due to
      surgeon's experience and local traditions, however, a standardized rather than a
      tailored approach is often offered to the patient. An inferior fornix and/or
      upper skin crease incision can be used for infero medial and/or lateral, bony
      and/or fat decompression. As an alternative the swinging eyelid technique,
      offering an adequate access to the bony orbit and to the orbital fat compartments
      is a versatile technique that can virtually be used as a standard approach for
      the greatest majority of patients needing decompression surgery. Orbital
      decompression by coronal incision is an invasive technique and for this not to be
      used as a standard approach to orbital decompression. Nevertheless, it is not to
      be abandoned as it can be an additional tool in surgeons' hands when dealing with
      patients who can better benefit out of a particular, tailored rather than a
      standardised approach. Many are the circumstances in which this may happen. Major
      complications associated with the coronal approach have been mainly described in
      small series, where only a few patients per year were operated. In this respect
      it is therefore unavoidable to emphasize that each technique has its own learning
      curve and it may be difficult to differentiate the effects of each technique from
      the experience of the surgeon.

PMID- 19839881
TI  - A step towards individualized, anatomy-based surgical concepts for orbital
      decompression in Graves' orbitopathy.
AB  - The surgical armamentarium for orbital decompression in Graves'orbitopathy (GO)
      includes techniques for orbital wall resection using local incisions, but also
      techniques for orbital rim advancement or resection of the greater sphenoid wing,
      which require a coronal or even transcranial approach. Up to now the choice of
      technique rather depends on the surgeon;s preference than on objective criteria.
      The goal of our CT-based research project is to define morphological orbital
      parameters which potentially could influence the result of a given technique for
      orbital decompression in thyroid eye disease. Based on the results
      individualized, anatomy-based surgical concepts could be established.

PMID- 19839882
TI  - Thyroidectomy in Graves' disease: subtotal, near total or total?
AB  - Thyroidectomy is one of the possible therapeutic options in Graves' disease as
      are antithyroid drugs and (131)radioiodine. Emerging data reveal an advantage of
      total thyroidal ablation as the method of choice in patients with impending or
      overt Graves' orbitopathy. Pros and cons are discussed as presented at the 1st
      Swiss Symposium on Thyroid Eye Disease in Pontresina, Switzerland in December
      2007.

PMID- 19839883
TI  - Squint surgery in TED -- hints and fints, or why Graves' patients are difficult
      patients.
AB  - Endocrine ophthalmopathy is the most common cause of acute onset diplopia in
      middle aged or older individuals. Ocular muscle involvement is characterized by
      myositis followed by fibrosis: this causes a stiffness and a shortening of the
      muscles involved with restriction of ocular movements: so the impairment of
      rotation is due to a mechanical obstacle and not to a paresis. Prisms are rarely
      useful in relieving diplopia and the majority of symptomatic patients need squint
      surgery. Timing of surgery is very important and two considerations are to be
      kept in mind: first, the systemic disease must be in remission and the ocular
      deviation must be stable for at least six months; second, if more than one
      surgical procedure is needed for the ophthalmopathy, muscle surgery has its right
      place after orbital surgery and before lid surgery. Obviously dealing with
      restrictive disorders, surgery is based on weakening procedures of the affected
      muscles: identifying the affected muscles is of crucial importance and may be
      sometime difficult for the presence of misleading signs; great advances have been
      made in surgical technique with the development of adjustable sutures and of
      topical anesthesia. Prognosis is usually good with more than 80% of patients
      recovering a useful field of binocular single vision with one procedure and more
      than 90% with two or more procedures.

PMID- 19839884
TI  - Rituximab in the treatment of thyroid eye disease: science fiction?
AB  - Lately, monoclonal antibodies directed to molecules of the immune system have
      become available. Rituximab (RTX) is a humanized chimeric anti-CD20 monoclonal
      antibody which blocks the activation and differentiation of B cells. The
      rationale for use in Graves' disease (GD) and orbitopathy is the potential effect
      on B-cell mediated immunity. Transient B cell depletion may modify the active
      inflammatory phase of thyroid eye disease (TED). We have studied nine patients
      with GD, of whom seven had active TED and two only lid signs. All but one
      patients showed both CD20+ cells and CD19+ cells depletion with the first RTX
      infusion, while one had persistent 3-5% CD19+ cells. RTX was well tolerated and
      only minor side effects were reported in three patients at first infusion.
      Circulating antithyroglobulin, antithyroperoxidase and anti-TSH receptor
      antibodies did not change significantly and did not correlate to CD20+ depletion.
      The clinical activity score value was 4.7+/-0.5 before therapy and 1.8+/-0.8 at
      the end of follow-up (P<0.0001). Proptosis decreased after RTX in both patients
      with active TED (P<0.0001) and those with lid signs (P<0.003). The degree of
      inflammation (NOSPECS Class 2) decreased (P<0.001). We did not record disease
      relapse at any time during follow-up, even after B cell return in peripheral
      blood. The results of this open trial on rituximab in TED suggest that the drug
      is effective in improving the disease clinical course.

PMID- 19839885
TI  - Can autoimmunity against calsequestrin explain the eye and eyelid muscle
      inflammation of thyroid eye disease?
AB  - Extra-ocular and upper eyelid (levator) muscle damage in thyroid orbitopathy may
      be due to autoimmunity against eye muscle auto antigens. The main antigen appears
      to be the calcium binding protein calsequestrin. In this study we have tested for
      T lymphocyte sensitization to calsequestrin in patients with Graves' disease,
      with and without orbitopathy, in standard proliferation assay. We have also
      tested total RNA prepared from thyroid tissue of patients with Graves' disease
      with and without orbitopathy for expression across 20,589 genes using micro array
      analysis technology. We were looking for differences in gene expression between
      the two groups which might provide information about the early thyroid events
      that lead to the development of eye muscle autoimmunity. Positive lymphocyte
      reactivity to calsequestrin was demonstrated in 59% of Graves' patients with
      orbitopathy, 33% without evident ophthalmopathy and in 43% of patients with
      Hashimoto's thyroiditis and upper eyelid retraction (UER). Two hundred and ninety
      six genes were identified to be differentially expressed between in patients with
      Graves' disease with and without orbitopathy. Of these, the cardiac calsequestrin
      gene CASQ2 was the most highly up regulated, 2.2-fold. The closely related
      skeletal muscle calsequestrin gene CASQ1 was also up-regulated, 4.1 fold, but
      this was not significant, while genes encoding the thyroid antigens
      thyroglobulin, thyroid peroxidase and the TSH-receptor were not differentially
      expressed. These findings provide further evidence for a prominent role of
      autoimmunity against calsequestrin in the pathogenesis of the eye muscle
      components of thyroid orbitopathy.

PMID- 19839886
TI  - Graves' disease associated with primary systemic sclerosis.
AB  - Graves' disease can be associated with other autoimmune disorders. Primary
      systemic sclerosis (PSS) is such a disease characterised by multi-organ fibrosis.
      Abnormal thyroid antibody titres and hypothyroidism as well as hyperthyroidism
      have been observed in PSS patients. Specific and idiopathic inflammatory
      disorders are an important differential diagnosis in Graves'orbitopathy (GO).
      Mycophenolate mofetil (MM) is an immunosuppressive drug which depletes guanosin
      nucleotides in proliferating B-and T-lymphocytes. We describe the effect of MM on
      the endocrine orbitopathy of a patient with PSS.

PMID- 19839887
TI  - Five-year cycle of basal cell carcinoma management re-audit.
AB  - AIM: To complete a 5-year audit cycle for all malignant lid tumours treated by
      one consultant (Stafanous) and re-audit the first work done in 2000 and
      2001/2002. The main aim was to find out the recurrence rate and presence of new
      lesions in 5-years' follow-up and determine whether it is safe to discharge
      patients after histological clearance and satisfactory reconstruction outcome
      rather than 5 years' follow-up. METHOD: Retrospective audit from January 2000 to
      December 2006. The collected data was: Site and type of lesions, type of surgery,
      recurrence rate and new lesions. RESULTS: Out of 112 cases identified, 104 were
      Basal Cell Carcinoma (BCC), 4 Squamous Cell Carcinoma (SCC), 3 Sebaceous Gland
      Carcinoma (SGC) and 1 Malignant Melanoma (MM). 68/112 had biopsy before
      definitive surgery and 44/112 had surgery without preceding biopsy. 54/112 had
      one stage surgical excision and 58/112 had modified Moh's surgery in 2-4 theatre
      sessions. Only 1/112 had recurrence at the same site during the follow-up period
      and 5 had new lesions at different periorbital sites. CONCLUSION: There was no
      evidence of significant recurrence to justify the 5-years' follow-up. Patients
      with histologically cleared tumours and satisfactory functional and cosmetic
      reconstruction outcome can safely be discharged to their GP and should be re
      referred for new lesions. The functional and cosmetic outcome of the
      reconstruction was generally satisfactory.

PMID- 19839888
TI  - Malignant lymphoproliferative disorders extending into the orbit from the
      paranasal sinuses.

PMID- 19839889
TI  - Malignant lymphoproliferative disorders extending into the orbit from the
      paranasal sinuses.
AB  - BACKGROUND/AIMS: To describe the clinical features, imaging, histologic spectrum,
      treatment and prognosis of patients with malignant orbital lymphoproliferative
      disorders extending from the paranasal sinuses. METHODS: Patients were culled
      from the University of British Columbia Orbit Clinic (1977-2004) and their
      clinical charts, imaging and pathology specimens reviewed. RESULTS: The study
      included 6 patients with non-Hodgkin's lymphoma (NHL) and 5 multiple myeloma
      (MM). Orbital symptoms at presentation were periorbital swelling, diplopia,
      proptosis and pain. Major clinical findings were globe displacement, abnormal
      ocular movements, periorbital fullness, fifth nerve hypoesthesia and inflammatory
      signs. Imaging showed a soft tissue mass in one or more sinuses invading the
      orbit. Three NHL patients were still alive at last follow-up with one patient
      lost to follow-up. Two NHL patients and all MM died. CONCLUSION: Presenting
      symptoms of malignant orbital lymphoproliferative disorders extending from the
      paranasal sinuses include mass effect occasionally with infiltrative and
      inflammatory characteristics accompanied by symptoms of sinus disease. On
      imaging, a soft tissue mass in the sinuses and orbit with bone destruction is
      commonly seen. Biopsy is essential for conclusive diagnosis. Treatment should be
      initiated promptly as local symptoms are frequently relieved and survival is
      possible, especially in cases of NHL.

PMID- 19839890
TI  - Genetic testing in orbital tumors.
AB  - OBJECTIVE: This review aims to discuss the clinical application of cytogenetic
      and molecular testing in the diagnosis and prognosis of orbital tumors and, in so
      doing, highlight the basis of these methods, their advantages, and limitations.
      SUMMARY: Specific chromosomal aberrations are detected in many
      lymphoproliferative neoplasms, soft tissue tumors, and in a few benign tumors of
      the orbit. Detection of these characteristic chromosomal translocations is most
      helpful to refine the diagnosis and classification, especially when the tumor is
      poorly differentiated and shows overlapping morphological features with another
      tumor type. This review outlines orbital tumors with characteristic chromosomal
      translocations and the relative frequency of detecting the genetic mutation.
      Various genetic techniques are available for genetic testing, including
      karyotyping, fluorescence in situ hybridization (FISH), reverse transcriptase
      polymerase chain reaction (RT-PCR), and genomic polymerase chain reaction (PCR).
      As yet, the newer methods of array-comparative genomic hybridization (array-CGH)
      and expression profiling are most commonly used in research settings or in large
      specialist centers, and their general application to cancer diagnostics is
      limited by their cost. Therefore, this review focuses on the methodologies that
      should be available to most diagnostic units. It is true that "one size does not
      fit all" in this field and that a combination of molecular techniques may be
      needed to confirm results at the genomic and transcriptional levels.

PMID- 19839891
TI  - Orbital cyst associated with ocular pit in an adult without microphthalmos.
AB  - We describe an adult without microphthalmos who developed an acquired compressive
      optic neuropathy secondary to an orbital cyst which showed direct communication
      with an optic disc pit. Such pits may be revealed by late complications such as
      orbital compressive cyst of the optic nerve, even in previously normal adult
      patients.

PMID- 19839892
TI  - Role of trichloroacetic acid in treating posterior conjunctival cyst in an
      anopthalmic socket.
AB  - Orbital cysts in anophthalmic socket are infrequent. Most of the cysts reported
      are anterior and the inability to retain a formerly well-fitted prosthesis is the
      most common symptom. We present a posterior conjunctival cyst developed after a
      dermo-fat graft reconstruction in an eviscerated socket. Eleven years after
      evisceration surgery due to irreparable ocular trauma an extrusion of the orbital
      implant occurred. Removal of the orbital implant and a socket reconstruction with
      dermis fat graft was done. Three years later, the patient again returned back to
      the treating ophthalmologist with complaint of an inability to retain the
      formerly well-fitted artificial prosthesis. A detailed ophthalmic examination
      failed to reveal any abnormality. The CT scan showed a posteriorly located
      conjunctival cyst in the right orbit. Tricholoroacetic acid (TCA) was injected
      intracystically into the conjunctival cyst. Ten months of follow-up did not show
      any recurrence of the conjunctival cyst and allowed complete tolerance of the
      prosthesis. This case report highlights the role of tricholoacetic acid in
      treating a posteriorly located conjunctival cyst in an anophthalmic socket.

PMID- 19839893
TI  - Autologous orbicularis muscle for filling facial folds-an experimental and
      clinical study.
AB  - PURPOSE: To present a technique for filling facial folds by using autologous
      orbicularis oculi muscle, based on an experimental model. METHODS: two studies
      are presented: (1) an experimental study using 15 albino guinea-pigs from which a
      strip of the sural triceps muscle was removed and implanted in the subcutaneous
      tissue of the dorsal area. The animals were sacrificed 7, 30 and 60 days after
      the implantation, and the material was histologically evaluated. And (2) an
      interventional prospective clinical trial carried out on 20 patients referred to
      blepharoplasty surgery. They received autologous preseptal orbicularis muscle for
      filling facial folds. The results where evaluated by patients satisfaction and
      clinical exam. RESULTS: the sural tricep muscle, when implanted in the
      subcutaneous tissue, resulted in fibrosis. The patients whom received autologous
      orbicularis muscle implanted for filling facial folds showed that the procedure
      can be successfully carried out. CONCLUSIONS: autologous preseptal orbicularis
      muscle is a good material for filling facial folds. Cicatricial tissue will be
      formed on its implantation site, filling the tissue gap that forms the folds on
      the skin.

PMID- 19839894
TI  - Monocanalicular versus bicanalicular intubation in external dacryocystorhinostomy
      for primary acquired nasolacrimal duct obstruction.
AB  - PURPOSE: Monocanalicular intubation offers potential advantages over
      bicanalicular intubation including ease of removal and use of only one
      canaliculus. Recent reports suggest equal outcomes with both types of tubes for
      nasolacrimal intubation. This study aimed to evaluate the outcome of
      monocanalicular intubation during external dacryocystorhinostomy. METHODS: Fifty
      seven lacrimal systems of 54 adults with primary acquired nasolacrimal duct
      obstruction were prospectively randomized into two cohorts for either
      bicanalicular intubation (n = 29) or monocanalicular intubation (n = 28) during
      external dacryocystorhinostomy. All subjects had their symptoms evaluated
      subjectively according to a modified Munk scale and objectively by the dye
      disappearance test along with probing and irrigation, pre- and post-operatively.
      Complete success was defined as a total disappearance of symptoms, partial
      success as an improvement with some residual symptoms, and failure as an absence
      of improvement or worsening of symptoms at the last follow-up. Patients with
      concurrent lid or ocular pathology were excluded. RESULTS: Bicanalicular subjects
      had a significantly higher complete success rate (21/29, 72.4%) compared to the
      monocanalicular group (12/28, 42.9%) (p = 0.03). Complications included 3 slit
      punctuae and 2 early tube removals with bicanalicular intubation; 6 temporary
      superficial punctate keratopathies, 1 punctal stenosis and 4 premature tube
      losses occurred with monocanalicular intubation. CONCLUSIONS: Patients with
      monocanalicular intubation during external dacryocystorhinostomy had a
      significantly lower success rate than patients with bicanalicular intubation in
      the treatment of nasolacrimal duct obstruction.

PMID- 19839895
TI  - Does the timing of silicone tube removal following external dacryocystorhinostomy
      affect patients' symptoms?
AB  - AIMS: To investigate whether the timing of silicone tube removal after external
      dacryocystorhinostomy (EXT-DCR) for lacrimal outflow obstruction affects outcome.
      METHODS: Retrospective chart review and follow-up by telephone survey of 205
      consecutive patients undergoing EXT- DCR. Long-term success was evaluated by
      telephone survey. RESULTS: Full data was collected in 180 out of 205 DCRs. Ninety
      four tubes (52.3%) were removed routinely between 2 and 4 months after surgery,
      24 tubes (13.3%) were removed before the planned 2-month period and 62 tubes
      (34.4%) were removed after the planned 4-month period. The three groups (early,
      routine and late) were comparable in terms of age, gender distribution, mode of
      anaesthesia, proportion of repeat EXT-DCRs and seniority of surgeon. The mean
      follow-up period was 3 years and 10 months. One hundred and twenty-eight of the
      155 patients (82.5%) were contactable by phone. In the routine tube removal
      group, at the time of follow-up, 65.1% experienced complete symptom resolution,
      25.4% experienced partial symptom resolution, 6.3% experienced no symptom
      resolution and 3.2% experienced worse symptoms. In the early tube removal group,
      at the time of follow-up, 63% experienced complete symptom resolution, 32%
      experienced partial symptom resolution and 5% experienced no change in symptoms.
      In the late tube removal group, at the time of follow-up, 70% experienced
      complete symptom resolution, 21.5% experienced partial symptom resolution and
      8.5% experienced no symptom resolution. There was no statistically significant
      difference in the outcome of the three groups. CONCLUSIONS: Our experience and
      this study suggest that timing of silicone tube removal does not influence
      surgical success in EXT-DCR regardless of the cause of early or late tube
      removal.

PMID- 19839896
TI  - Lacrimal gland uptake of gallium (67Ga) citrate in patients without ocular
      pathology.
AB  - PURPOSE: To report a series of patients with bilateral lacrimal gland uptake of
      Gallium (67Ga) Citrate in patients without ocular pathology and to assess the
      degree to which this can be a normal phenomenon. METHODS: We present an index
      case of lacrimal gland uptake of Gallium (67Ga) Citrate in a patient without
      lacrimal pathology and a subsequent retrospective review of all Gallium scans
      performed at the Bristol Royal Infirmary, UK from 2002 to 2008. Patients who
      demonstrated Ga67 uptake within the lacrimal glands were identified and case
      notes from all scans were retrieved and reviewed. The notes were analysed to
      determine the rationale for the gallium investigation as well as whether there
      was any preexisting ocular pathology. RESULTS: Retrospective review demonstrated
      that 21 gallium scans were performed from 2002 to 2008, from which 4 patients
      demonstrated bilateral lacrimal gland Ga67 uptake with no evidence of past or
      current lacrimal/ocular pathology. On the basis of our review, we report that
      bilateral gallium uptake is not a specific finding, occurring in normal
      individuals with no history or symptoms of ocular or orbital pathology.

PMID- 19839897
TI  - Orbital cellulitis in children-medical treatment versus surgical management.
AB  - INTRODUCTION: Ophthalmologists differ in their threshold for surgical management
      in paediatric patients with orbital cellulitis. We studied the management choices
      and outcome of children admitted with this disorder. MATERIAL AND METHODS: A
      retrospective review was performed on patients with orbital cellulitis admitted
      between January 2001 and December 2004 to a tertiary paediatric referral centre
      in Singapore. The patients were studied for age, associated systemic disease,
      medical treatment, drainage procedure undertaken, organism isolated and outcome.
      Statistical methods were applied for comparing medical treatment with surgical
      treatment with respect to recovery time, recurrence, and time between the
      presentation of patient and initiation of treatment. RESULTS: Twenty patients
      were studied. Average age was 5.5 years. 5/20 (25%) had a preceding history of
      upper respiratory tract infection. From CT findings, we came to know that 3/20
      (15%) were due to isolated ethmoiditis, 5/20 (25%) had obstruction of the
      osteomeatal complex of the paranasal sinuses, 2/10 (10%) had intracranial
      abscesses due to frontal sinusitis. 4/20 (20%) had all 4 ipsilateral paranasal
      sinuses infected. 2/20 (10%) had preseptal cellulitis with posterior extension
      into the orbit. 2/20 (10%) had orbital cellulitis related to dacryoadenitis and
      2/20 (10%) had pansinusitis with orbital soft tissue stranding. 13/20 (65%) had
      orbital and /or endoscopic drainage. The remainder of the patients had good
      immediate response to sole medical treatment and did not require surgery. The
      most commonly isolated organism was Staphylococcus aureus 5/20 (25%). All
      patients recovered within a mean of 9.6 days with no complications or functional
      deficit. CONCLUSIONS: Paediatric orbital cellulitis can be treated conservatively
      or with surgical drainage. Indications for surgery include pansinusitis, large
      abscesses with significant mass effect, concurrent intracranial involvement, poor
      response to initial medical treatment and the presence of an orbital abscess and
      gas. Sole medical treatment worked well in children with no orbital abscess,
      small or medial abscesses as they tend to have a single organism infection. This
      is also of particular significance in young children below the age of one where
      endoscopic surgery can be technically difficult. Intracranial involvement
      occurred in association with frontal sinusitis and affected patients had the
      longest duration of hospitalization.

PMID- 19839898
TI  - Measurements of lacrimal glands from cadavers, with descriptions of typical
      glands and three gross variants.
AB  - OBJECTIVE: To measure cadaveric human lacrimal glands. METHODS: Excised lacrimal
      glands from 22 male and 23 female embalmed cadavers were stored in embalming
      fluid. They were then blotted, weighed, and measured using dividers and a digital
      micrometer. RESULTS: Besides the typical gland (Type I), three gross variants
      were found. The subencapsulated variant (Type II) has dense connective tissue
      covering its deep surface. This would prevent the usual horizontal positioning of
      the lobes relative to the levator palpebrae superioris aponeurosis (lpsa),
      causing the latter to extend but minimally beneath the free edge of the orbital
      lobe. Consequently, the gland lies mainly beside the globe and angulated parallel
      to the lpsa. Its adjacent palpebral lobe lies beneath the latter. The bilayered
      variant (Type III) has its smaller orbital lobe's deep surface affixed above its
      large, ovoid palpebral lobe. Most of the gland droops beside the globe except for
      the edge of its orbital lobe which lies above the edge of the lpsa and beneath
      which the palpebral lobe's anteromedial portion lies. The macrovariant (Type IV)
      resembles the typical gland. However, between its big lobes is an unusually large
      gape for the lpsa. CONCLUSIONS: Variant lacrimal glands are common (51.1%). Three
      types have been identified. The subencapsulated (26.7%) and bilayered (22.2%)
      types are the more common ones. Only one macrovariant (2.2%) specimen was found.
      Several dimorphisms exist in the typical and subencapsulated types, specimens
      from male cadavers being larger.

PMID- 19839899
TI  - Cost-related antibiotic dosage omissions-challenge for orbital cellulitis
      management in resource poor communities.
AB  - BACKGROUND: Orbital cellulitis is a medical emergency with potential vision and
      life threatening complications. AIM: To highlight clinical presentation and
      challenges in the management of orbital cellulitis in resource poor communities
      of southwestern Nigeria. METHOD: Retrospective review of patients managed for
      orbital cellulitis at the Wesley Guild Hospital, Ilesa, Nigeria for biodata,
      socioeconomic status, clinical presentation, compliance to prescribed medications
      and treatment outcome. Data was analyzed using SPSS version 11. RESULT: Seventeen
      patients with mean age and standard deviation of 10 +/- 9.9 years were managed
      for orbital cellulitis. Thirteen (76.5%) females and 4(23.5%) males giving a male
      to female ratio of 1:3.3 (p = 0.03). Most patients (94.1%) belonged to low
      socioeconomic status and sinusitis was the most common predisposing factor. 10
      (58.8%) had intravenous antibiotics only while 7(41.2%) had surgical drainage of
      abscess in addition. Delayed and irregular administration of antibiotics was
      observed in 9 (52.9%) patients due to lack of funds thus necessitating change of
      choice in antibiotics. Complication include ptosis 3(17.6%), corneal opacity 2
      (11.8%), optic atrophy 1(5.9%) and 1(5.9%) meningitis and death 1(5.9%).
      CONCLUSION: Cost and affordability should be major determinants of choice of
      empirical antibiotics in resource poor communities to ensure timely and regular
      treatment and improve prognosis in management of orbital cellulitis.

PMID- 19839900
TI  - Orbital metastasis: clinical features, management and outcome.
AB  - PURPOSE: To review the clinical features, treatment, outcome and survival of
      metastatic tumors of the orbit. MATERIALS AND METHODS: Retrospective, non
      comparative, chart review of 80 patients with orbital metastasis treated in four
      tertiary orbital centres in Australia. RESULTS: The study included 80 patients of
      which, 44 were male with a mean age of 60 years. Orbital involvement commonly
      presented late in a multisystemic disease; however, the orbit was the first
      presentation in 15% of the cases. Diplopia (48%), pain (42%), and visual loss
      (30%) were the commonest symptoms at presentation; whereas proptosis (63%),
      strabismus (62%), and visual loss (41%) were the most frequent clinical signs.
      Computed tomography commonly showed a solid enhancing mass (42 cases) located
      within the orbital fat (43%), or enlarging an extraocular muscle (28%). Breast
      carcinoma (29%), melanoma (20%), and prostatic cancer (13%) were the most
      frequent histological types. Treatment was often multi-disciplinary and
      modalities included radiotherapy, chemotherapy, hormone therapy, surgery, and
      immunotherapy. Survival was limited to 1.5 years after diagnosis independent of
      the histological type, with 29% of patients alive after 17 months follow-up.
      CONCLUSIONS: A high index of suspicion and appropriate intervention with
      histological diagnosis can help in the management and quality of life in patients
      with metastatic orbital disease. Overall survival is limited and we encountered
      statistical limitations proving differences in the survival based on the sub-type
      of primary tumour involved. Metastatic orbital melanoma presented a higher
      incidence when compared with previous studies, probably due to the increase
      frequency of skin found in the Australian population.

PMID- 19839901
TI  - Group C streptococcal subperiosteal abscess of the orbit.
AB  - Group C Streptococcus is a well recognised pathogen in acute pharyngitis and
      sinusitis. To our knowledge group c streptococcus has not been reported to cause
      orbital cellulitis or subperiosteal abscess. We wish to report a case of a child
      with orbital subperiosteal abscess caused by Group C streptococcus.

PMID- 19839902
TI  - Breast cancer in a male with thyroid-associated orbitopathy and subclinical
      hyperthyroidism: a rare occurrence.
AB  - We present a case of a biochemically euthyroid male with active moderately severe
      thyroid associated orbitopathy who was coincidentally found to have breast
      carcinoma. The relationship between thyroid disease and breast carcinoma is
      discussed. The authors recommend that an enquiry of any breast lump or
      abnormality should be undertaken in all patients with thyroid disease.

PMID- 19839903
TI  - Periorbital tuberculosis in a young man: a case report.
AB  - BACKGROUND: Tuberculosis is an endemic disease in developing countries which may
      involve various organs. Soft tissue involvement including periorbital tissues is
      very rare, and often this involvement is accompanied by the involvement of other
      body organs such as lungs. Most of the patients suffering from periorbital
      infections have underlying diseases and diagnosis of these infections without
      concomitant involvement of other parts of body is often complex. CASE
      PRESENTATION: In this paper, a periorbital tuberculous infection is described. A
      17-year-old male with chronic periorbital mass underwent surgical and medical
      treatment and the mass recurred. Culture and microscopic studies of the specimen
      showed mycobacterium tuberculosis. The patient was treated for a periorbital
      tuberculous infection for a 6-month period with antituberculous regimen and was
      cured. CONCLUSION: Periorbital tuberculous infection may occur in the absence of
      underlying factors or active tuberculosis in the rest of the body organs or a
      history of tuberculosis infection.

PMID- 19839904
TI  - An unusual case of retrobulbar arachnoid cyst and its management.
AB  - Arachnoid cysts are collection of cerebrospinal fluid contained inside a cavity
      lined by leptomeninges. It constitutes 1% of all intracranial tumours mostly
      present in the middle cranial fossa. Retrobulbar arachnoid cyst in elderly
      persons are a rare occurrence. We report a rare case of retrobulbar arachnoid
      cyst with ophthalmic manifestations and its effective management. CT-guided
      aspiration of the cyst and subsequent cytological and biochemical test revealed
      an arachnoid cyst. Patient is on a 5-year follow up without recurrence and
      improvement of the vision in the affected eye.

PMID- 19839905
TI  - Microphthalmia with huge cyst: a simple technique for excision.
AB  - PURPOSE: Is to present a simple technique for complete excision of microphthalmia
      and its huge cyst. PATIENTS: Five patients with microphthalmia and huge cyst were
      included. The pathology was bilateral in one case. Lateral canthotomy was
      performed in all cases. The 4 recti of the small eye were exposed and dis
      inserted with application of 4 tractional sutures at the insertion sites. Gentle
      traction and blunt dissection with protection of the cyst by malleable retractor
      were used to release the cyst gradually. The optic nerve was clamped and
      cauterized. By cutting the optic nerve, the microphthalmic eye and its huge cyst
      came out easily. RESULTS: In no patient was the cyst was ruptured or incompletely
      excised. CONCLUSION: This technique is simple, fast and effective for complete
      excision of the microphthalmia and its huge cyst completely.

PMID- 19839906
TI  - Atypical presentation of a case of solitary fibrous tumor of the orbit.
AB  - PURPOSE: To describe a rare case of solitary fibrous tumor of the orbit in a
      child, clinically misdiagnosed as arterious hemangioma. METHODS: A nine-year-old
      child presented a hard-elastic palpable mass located in the right inferotemporal
      orbit. Computed tomography, orbital pulsed-wave Doppler and internal carotid
      artery angiography consented diagnosis of high-vascularization mass probably
      related to arterious hemangioma with feeder vessel arising from a branch of
      ophthalmic artery. The orbital mass was surgically removed. RESULTS: The
      histological examination showed mesenchimal tumor, CD34 positive, related to
      solitary fibrous tumor of the orbit. CONCLUSIONS: Solitary fibrous tumor of the
      orbit should be considered in the differential diagnosis of arterious hemangioma.

PMID- 19839907
TI  - An unusual case of recurrent subconjunctival haemorrhage causing yellow-brown
      discolouration due to haemosiderin deposition.
AB  - The authors describe an unusual case of striking unilateral yellow-brown
      discolouration of the conjunctiva in a 33-year-old man. A biopsy from an elevated
      conjunctival area showed a brown pigmentation to be haemosiderin and
      haemogranulomatous inflammation most probably due to recurrent subconjunctival
      haemorrhage.

PMID- 19839909
TI  - Ectopic orbital brain diagnosed 20 years after symptomatic presentation.
AB  - Ectopic brain in the orbit is a rare entity with only 14 other case reports in
      the literature. This case is unique in that symptomatic presentation occurred 20
      years prior to diagnosis. Symptoms are generally due to mass effect. We report an
      unusual case of diplopia secondary to ectopic orbital brain and a review of the
      literature.

PMID- 19839908
TI  - Inverted papilloma arising primarily from the lacrimal sac.
AB  - A 24-year-old female was referred with epiphora and a non-tender swelling within
      the right lacrimal fossa, present for 6 months. There were no previous episodes
      of dacryocystitis. Computed tomography showed a homogenous mass within the
      lacrimal fossa without contrast enhancement. Pathology following resection of the
      whole lacimal sac revealed the presence of an inverted papilloma (IP) with a
      sharp transition between the papilloma and the normal lacrimal duct epithelium.
      In situ hybridisation was positive for low risk HPV subtypes. An IP is a benign
      but infiltrative epithelial neoplasm with malignant potential characterised by a
      high recurrence rate. Majority of cases arise from the nasal wall and paranasal
      sinuses. In this case report, we demonstrate an IP confined to the lacrimal sac
      with clear-cut pathology proof, which implicates the lacrimal sac as a primary
      site of origin.

PMID- 19839910
TI  - Giant iatrogenic orbital inclusion cyst of acute presentation.

PMID- 19839911
TI  - Extramedullary pasmacytoma masquerading as chalazion.
AB  - Extramedullary plasmacytoma (EMP) is a rare entity that belongs to the category
      of non-Hodgkin lymphoma. EMP make up 4% of all plasma cell tumors and occur
      mainly in the upper aerodigestive tract. Primary plasmacytoma involving the orbit
      is rare. There is a relation between solitary plasmacytoma and subsequent
      development of multiple myeloma. As no predictors of progression have been
      identified patients need indefinite follow-up. The authors report a case of EMP
      involving the eyelid in an otherwise healthy adult female.

PMID- 19839912
TI  - Yellow lid sign in Wegener's granulomatosis.
AB  - Orbital manifestations in Wegener's granulomatosis develop in over 50% of
      patients. Ischemic vasculitis and optic nerve compression result in visual
      impairment. This case report highlights the importance of the yellow lid sign in
      the diagnosis of orbital granulomatosis as well as provides an explanation for
      the reversal of this phenomenon.

PMID- 19839913
TI  - Acute dacryocystitis causing orbital cellulitis and abscess.
AB  - PURPOSE: Acute dacryocystitis commonly presents as preseptal cellulitis as
      lacrimal sac lies anterior to the orbital septum and hence infection localizes in
      the preseptal space. The purpose of this study is to describe presentation and
      management of cases of acute dacryocystitis presenting as orbital cellilitis and
      abscess secondary to acute dacryocystitis. METHOD: This retrospective, non
      comparative, interventional case series included 6 patients presenting with
      orbital cellulitis and abscess secondary to acute dacryocystitis. All patients
      underwent drainage of abscess under general anesthesia. External
      dcaryocystorhinostomy was advised as the definitive treatment for all pateints.
      RESULT: Abscess was localized in the extraconal space in 4 patients and in the
      intraconal space in 2 patients. Patients with intraconal abscess had visual loss
      on presentation while vision could be preserved in patients with abscess in
      extraconal space. Both patients with intraconal abscess had history of acute
      dacryocystitis. CONCLUSION: Acute dacryocystitis is an ophthalmic emergency that
      can cause orbital cellulitis with abscess formation, and even vision loss, if
      left untreated.

PMID- 19839914
TI  - Large orbital osteoma arising from orbital roof: Excision through an upper
      blepharoplasty incision.
AB  - Osteoma is the most common benign tumor of facial bony structure. Intraorbital
      extension is extremely rare. We report a case of intraorbital, pedicled osteoma
      originating from the left orbital roof. The patient's ophtalmological examination
      revealed; only light perception due to the severe amblyopia and posterior
      capsular opacification in the right eye, and complete visual acuity in the left.
      His left eye was proptotic and directed to downward lateral gaze position. Using
      upper blepharoplasty incision, the osteoma was completely excised. There were not
      any postoperative complications and all ocular symptoms in the left eye were
      resolved after 1 month.

PMID- 19839915
TI  - Rare orbitocranial tumour in an adult.
AB  - A 35-year-old lady presented with recurrent episodes of painful right upper lid
      swelling and ptosis of 6 months' duration. The symptoms would subside with oral
      antibiotics and painkillers. She had also been undergoing treatment for one year
      for multiple painful osteolytic lesions in the long bones and axial skeleton for
      which no definite diagnosis had been made, despite several radiological and
      serological investigations having been performed. Computed tomographic scan
      showed a soft tissue lesion in the superolateral part of the right orbit with
      erosion of the adjacent bone. Lacrimal gland biopsy showed non-specific
      inflammatory changes. She was referred for full work-up to exclude lymphoma and
      metastasis. Magnetic resonance imaging revealed an enhancing soft tissue mass in
      the right anterior cranial fossa eroding the lateral orbital wall and extending
      into the orbit. Another mass encased the superior sagittal sinus. Bone marrow
      biopsy showed near total replacement of marrow cells by a round cell tumour.
      Immunohistochemical studies revealed that the tumour cells expressed neuron
      specific enolase and chromogranin. The pathological findings suggested a
      diagnosis of neuroendocrine tumour though neuroblastoma could not be
      unequivocally ruled out. (131) I-metaiodobenzylguanidine scan showed no uptake.
      Radiologic studies suggested multiple bony metastases. No other site of primary
      tumour was found so there was a strong possibility of it being a primary orbito
      cranial neurogenic tumour. Neuroblastomas and neuroendocrine tumours are very
      rare in adults. The orbit is an unusual site for a primary of this nature. In
      addition, it is quite difficult to make a specific diagnosis in a less
      differentiated tumour.

PMID- 19839916
TI  - Re: "Use of high resolution microscopy coil MRI for depicting orbital anatomy,"
      ORBIT issue 27.2 (page 107-114)-answer to reader comments.

PMID- 19839917
TI  - Second hematologic malignancies after ABVD: Two case reports and a retrospective
      study of 183 Hodgkin lymphoma patients.

PMID- 19839918
TI  - A dose escalation study of docetaxel plus capecitabine in combination with
      oxaliplatin in patients with advanced solid tumors.
AB  - OBJECTIVES: Capecitabine (CAP), Oxaliplatin (OX) and Docetaxel (DOC) have shown
      considerable activity in a wide range of solid tumors. A phase I study was
      conducted in order to determine the maximum-tolerated dose (MTD) and dose
      limiting toxicities (DLTs) of their combination in patients with advanced solid
      tumors. PATIENTS AND METHODS: Twenty-one patients were enrolled. The patient's
      median age was 68 years, 15 were male, and 12 were chemo-naive. DOC was
      administered on day 1 as an 1-hour (iv) infusion at a standard dose of 50
      mg/m(2). OX was administered on day 1 as a 2-hour (iv) infusion at escalating
      doses ranging from 70-80 mg/m(2). CAP was administered orally on days 1 to 7 at
      escalating doses ranging from 2,000-2,750 mg/m(2) given as two daily divided
      doses. Treatment was repeated every two weeks. RESULTS: Six different dose-levels
      were examined. At dose-level VI, two of three enrolled patients presented DLTs
      (one patient diarrhea and asthenia grade 3 and another grade 3 diarrhea), and
      thus, the recommended MTD for future phase II studies is CAP 2,750 mg/m(2) , DOC
      50 mg/m(2) and OX 75 mg/m(2). A total of 121 treatment cycles were administered.
      Grade 3 neutropenia was observed in six (5%) treatment cycles and grade 3
      thrombocytopenia in one (1%). There was no febrile episode. Grade 3 asthenia was
      observed in three (14%) patients, grade 3 diarrhea in four (19%), grade 3
      neuropathy in one (5%), and grade 1/2 hand-foot syndrome in three (14%). Other
      toxicities were uncommon. There was no treatment related death. Four (29%) PRs
      and seven (50%) SD were observed among 14 evaluable patients. Responses were seen
      in patients with renal (n = 1), gastric (n = 2) and pancreatic (n = 1) cancer.
      CONCLUSIONS: These results demonstrate that CAP, DOC and OX can be safely
      combined at clinically relevant doses and this regimen merits further evaluation.

PMID- 19839920
TI  - Gemcitabine and capecitabine in combination for advanced anthracycline and taxane
      pre-treated breast cancer patients: A phase II study.
AB  - AIM: The aim of this study was to explore the clinical value of gemcitabine
      combined with capecitabine (GC) in heavily pre-treated patients with metastatic
      breast cancer. MATERIAL AND METHODS: All patients had failed anthracyclines and
      taxanes. In 14 patients (41%), more than two metastatic sites were diagnosed with
      bone (68%) and liver (62%) being the most prominent. Gemcitabine (1,250 mg/m(2),
      d1+8) and capecitabine (800 mg/m(2) twice daily, d1-14) were administered
      according to a 3-week schedule. The majority of patients received GC as 3rd or
      4th line chemotherapy for metastatic disease. Laboratory tests were done on day
      1+8 in cycles. Subjective toxicity was recorded according to the NCI-CTC v. 2.0
      criteria. Tumour evaluations were done every 12th week according to the RECIST
      criteria. The primary objective was to investigate time to progression. Secondary
      objectives were response rate with special focus on the proportion of patients
      achieving PR or SD of at least three months, toxicity and survival. RESULTS: A
      total of 34 patients were enrolled. All subjects are eligible for toxicity,
      response and time to event analyses. Treatment was given until progressive
      disease, severe toxicity or until the patient wanted to withdraw. The Kaplan
      Meier median time to progression was estimated to 4.3 months and the overall
      survival time to 13.7 months. Partial response was noted in 12 of 29 evaluable
      patients (41%). The best outcome amongst remaining patients was stable disease in
      nine (31%) or tumour progression in eight (28%). A delay of disease progression
      of more than three months was noted in 53% of the study population. The main side
      effect was granulocytopenia with 44% and 15% of patients suffering from grade 3
      or grade 4 events respectively however, no neutropenic infections were observed.
      Pre-dominant grade 3 subjective toxicities were: fatigue (21% of patients) and
      hand-foot syndrome (15% of patients). DISCUSSIONS: We investigated the value of
      the GC combination as a treatment for late stage breast cancer patients. Tumour
      progression was delayed and the treatment was well tolerated. We believe that the
      GC therapy can achieve meaningful palliation.

PMID- 19839921
TI  - Growth factor-rich plasma increases tendon cell proliferation and matrix
      synthesis on a synthetic scaffold: an in vitro study.
AB  - Numerous scaffolds have been proposed for use in connective tissue engineering.
      Although these scaffolds direct cell migration and attachment, many are
      biologically inert and thus lack the physiological stimulus to attract cells and
      induce mitogenesis and matrix synthesis. In the current study, a bioactive
      scaffold was created by combining a synthetic scaffold with growth factor-rich
      plasma (GFRP), an autologous concentration of growth factors derived from a
      platelet-rich plasma preparation. In vitro tendon cell proliferation and matrix
      synthesis on autologous GFRP-enriched scaffolds, autologous serum-enriched
      scaffolds, and scaffolds alone were compared. The GFRP preparation was found to
      have a 4.7-fold greater concentration of a sentinel growth factor (transforming
      growth factor-beta1) compared with serum. When combined with media containing
      calcium, the GFRP produced a thin fibrin matrix over and within the GFRP-enriched
      scaffolds. Cell proliferation assays demonstrated that GFRP-enriched scaffolds
      significantly enhanced cell proliferation over autologous serum and control
      groups at both 48 and 72 h. Analysis of the scaffolds at 14, 21, and 28 days
      revealed that GFRP-enriched scaffolds significantly increased the deposition of a
      collagen-rich extracellular matrix when compared with the other groups. These
      results indicate that GFRP can be used to enhance in vitro cellular population
      and matrix deposition of tissue-engineered scaffolds.

PMID- 19839922
TI  - Intercalation of erlotinib and pemetrexed in the treatment of non-small cell lung
      cancer.
AB  - Both the multi-targeted antifolate pemetrexed and the epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib have established roles
      in the treatment of advanced non-small cell lung cancer (NSCLC). Given different
      mechanisms of action and minimal overlapping toxicities, combinations of these
      agents have been considered. However, four previous phase III trials
      investigating concurrent chemotherapy with or without EGFR TKIs showed no
      clinical benefit. Based on preclinical data, we developed a model of
      pharmacodynamic separation to avoid potential negative interactions between
      chemotherapy and EGFR TKIs in tumors containing wild-type EGFR. This review
      summarizes the background, scientific rationale and early clinical data in
      support of intercalation of intermittent erlotinib dosing with pemetrexed as a
      means of achieving pharmacodynamic separation. Ongoing research efforts
      investigating this concept are reviewed.

PMID- 19839923
TI  - Pemetrexed: potential role in the adjuvant chemotherapy of non-small cell lung
      cancer.
AB  - Platinum-based doublet chemotherapy is now established as a standard of care in
      the adjuvant treatment of resected stage II and stage IIIA nonsmall cell lung
      cancer, and seems reasonable also in resected stage IB when the primary tumor
      measures > or =4 cm. Several issues remain unresolved, however, including
      individualized selection of both the optimal platinum (cisplatin vs carboplatin),
      and the optimal nonplatinum drug; and identification of patients who will not
      need chemotherapy ("surgically cured"), as well as patients who cannot benefit
      because of inherently drug resistant disease. Furthermore, while efficacy remains
      a priority, it is also necessary to improve the management of toxicity, both
      because it may compromise dose intensity and because it carries a risk of
      morbidity and even mortality. Other issues, such as the role of postoperative
      radiotherapy, the choice between neoadjuvant and adjuvant approaches, the role of
      targeted agents, and the possibility of harm and how it can be mediated, also
      merit serious attention. Finally the durability of benefit, the question of late
      toxicity, and the importance of smoking cessation are also open questions. I will
      discuss a potential role for pemetrexed in the adjuvant treatment of early stage
      nonsmall cell lung cancer with some of these issues in mind.

PMID- 19839924
TI  - The role of pemetrexed in lung adenocarcinoma, mixed subtype with
      bronchioloalveolar carcinoma features.
AB  - Bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar
      features (ADC-WBF) belong to the same anatomo-clinical entity and show very
      similar epidemiologic, clinical and biological characteristics. However there is
      a lack of consensus for the treatment of unresectable forms. Although epidermal
      growth factor receptor tyrosine kinase inhibitors and paclitaxel do have some
      efficacy, the aim of this review is to assess the role that pemetrexed, a new
      generation antifolate, could play in this context. Pemetrexed has proved to be
      particularly effective in advanced lung adenocarcinomas and unresectable
      mesotheliomas, and cases of major and sustained responses of ADC-WBF to
      pemetrexed have been reported. The preclinical rationale explaining this efficacy
      is that it inhibits the growth of BAC cell lines in vitro. BAC tumors overexpress
      FR-alpha, a protein involved in pemetrexed intracellular transport, at rates
      higher than those observed in lung adenocarcinomas and mesotheliomas and it would
      seem that pemetrexed efficacy is correlated to FR-alpha expression. The role
      played by thymidylate synthase expression level in sensitivity to pemetrexed also
      needs to be specifically explored in ADC-WBF. The results of two phase II trials,
      SWOG 0526 and IFCT 05-04, will hopefully provide decisive information on the
      relevance of pemetrexed in ADC-WBF management and the molecular predictors of
      response.

PMID- 19839925
TI  - The role of chemotherapy and radiation in the treatment of locally advanced non
      small cell lung cancer (NSCLC).
AB  - Approximately one out of every three patients with non-small cell lung cancer
      (NSCLC) has locally advanced disease that is surgically unresectable. If their
      performance status allows, it is current practice to treat these patients with a
      combination of chemotherapy and external beam irradiation. There have been
      several studies supporting the addition of chemotherapy to radiation,
      particularly when delivered concurrently. There is debate over which treatment
      agents and schedules are most optimal, even with the most proven treatments
      delivering only modest results, with high rates of local and distant disease
      failure. Advances in imaging and radiation planning and delivery technology have
      allowed for the potential for improvement of the therapeutic ratio by reducing
      normal tissue exposure and ensuring for more precise delivery, while new systemic
      agents show promising activity in NSCLC. Pemetrexed is a pyrrolopyrimidine-based
      folate anti-metabolite that works by inhibiting a variety of enzymes of
      thymidylate and purine synthesis, thus leading to cell stasis and death. Similar
      to other cytotoxic antifolates, pemetrexed has been shown in pre-clinical study
      to act as an effective radiosensitizer. At present, it is being studied in phase
      I and II studies when combined with other systemic agents and radiation therapy
      in the treatment of locally advanced NSCLC, and the results have been promising.
      It has the advantage of allowing for relatively safe delivery of full systemic
      doses when combined other agents and radiation therapy, a distinction over
      combined modality treatments. Its efficacy, particularly in non-squamous NSCLC,
      in phase I and II studies has lead to investigations in the phase III setting
      where a more defined role for pemetrexed in locally advanced non-squamous NSCLC
      will potentially be defined. This review summarizes the use of combined modality
      treatment in locally advanced NSCLC, outlines recent advances in radiation
      planning and treatment, and reviews the current data on the use concurrent
      chemoradiation regimens featuring pemetrexed.

PMID- 19839926
TI  - The role of pemetrexed combined with gemcitabine for non-small-cell lung cancer.
AB  - Pemetrexed is a multitargeted antifolate that inhibits at least three folate
      dependent enzymes involved in DNA synthesis. Gemcitabine is a broadly active
      pyrimidine nucleoside antimetabolite that is incorporated into DNA and causes
      chain termination. Both pemetrexed and gemcitabine, as single agents, have shown
      antitumor activity in a wide range of solid tumors, including non-small-cell lung
      cancer (NSCLC). Based on preclinical in vitro and in vivo synergism of the
      combination of pemetrexed and gemcitabine, the 2 drugs were studied in several
      phase I and II trials in patients with advanced NSCLC. The published studies
      found response rates between 13 to 31%, with overall survival times similar to
      established standard chemotherapy regimens. The grade 3 or 4 toxicities with this
      combination are mainly haematologic, dermatologic and transaminitis. In this
      paper, we review the pemetrexed-gemcitabine combination in the treatment of NSCLC
      patients with regards to the rationale, clinical activity as well as the future
      directions for this new 2-drug combination.

PMID- 19839927
TI  - The role of pemetrexed in second-line chemotherapy for advanced non-small cell
      lung cancer.
AB  - Despite improvements in first-line therapy for advanced NSCLC all patients with
      metastatic disease will progress at some point. Patients with favorable
      prognostic factors such as good performance status, non-squamous histology,
      stable weight, and perhaps female gender are more likely to receive second-line
      chemotherapy. Currently the United States FDA recognizes three single agents
      (docetaxel, erlotinib, and pemetrexed) as established for providing a benefit in
      patients who have experienced progression after first-line therapy. This review
      focus on the role of PEM in the treatment of advanced NSCLC in patients who have
      experienced disease progression during or after first-line therapy. The multi
      targeted antifolate pemetrexed is equivalent to docetaxel for second-line therapy
      and with less toxicity.

PMID- 19839928
TI  - Predictive markers for haematological toxicity of pemetrexed.
AB  - Pemetrexed is a multi-targeted anti metabolite that inhibits several key folate
      dependent enzymes in the thymidine and purine biosynthetic pathways, including
      thymidylate synthase. It is currently approved for use in patients with non-small
      cell lung cancer and malignant mesothelioma. The sporadic and unpredictable
      occurrence of haematological toxicities of pemetrexed leading to potentially life
      threatening complications during the early developmental phase, prompted urgent
      need to identify potential predictive factors for haematological toxicities from
      pemetrexed. There is a well established association between elevated plasma
      homocysteine concentration, which is indicative of impaired functional folate
      status, and increased risk of haematological toxicity from pemetrexed. The
      decrease in incidence of toxicity after vitamin supplementation confirms the
      importance of functional folate status as a predictor for haematological
      toxicity. We review other factors that have a documented impact on haematological
      toxicity, including pemetrexed schedule, and pharmacokinetic parameters that are
      indicative of the extent of drug exposure. Further potential factors are explored
      in this review, such as the genotype of the pemetrexed metabolising enzymes and
      varying incidences of polymorphism of these genotypes in different ethnic groups
      that may account for the ethnic differences in neutropenic response to
      pemetrexed.

PMID- 19839929
TI  - The role of pemetrexed in advanced non small-cell lung cancer: special focus on
      pharmacology and mechanism of action.
AB  - Pemetrexed is a newer antifolate drug that has been approved as first-line
      treatment for patients with advanced non-squamous, non-small cell lung cancer
      (NSCLC) in combination with cisplatin, and as single agent for relapsed or
      chemotherapy refractory NSCLC after platinum-containing chemotherapy, at a dose
      of 500 mg/m(2). Pemetrexed undergoes intracellular activation by poly-gamma
      glutamylation, that is essential for its antiproliferative activity.
      Polyglutamate derivatives mainly inhibit three key enzymes of intracellular
      folate metabolism, i.e. thymidylates synthase (TYMS), dihydrofolate reductase
      (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), with TYMS being
      the most relevant target. Pemetrexed undergoes rapid renal elimination as
      unchanged parent compound, with a terminal half-life of between two to five
      hours. In later clinical development, the usefulness of supplementation with
      folic acid and vitamin B(12) became evident, to control pemetrexed-related
      toxicity. The results from the phase III upfront registration study, a
      retrospective observational data, and a recent maintenance study of pemetrexed in
      NSCLC suggest histological subtype to be the most important predictive marker for
      clinical outcome in patients receiving pemetrexed, Pemetrexed is active in
      patients with non-squamous cell NSCLC while no benefit is seen in patients with
      squamous-cell histology, possibly as a result of different expression of
      intratumoral TYMS. These are important steps towards individualisation of
      anticancer treatment in patients with advanced NSCLC.

PMID- 19839930
TI  - Role of pemetrexed and platinums combination in patients with non-small cell lung
      cancer.
AB  - The incidence of lung cancer in 2007 is estimated to be 213,380 with 160,390
      deaths in the United States. It will contribute to 31% of male and 26% of female
      cancer-related deaths and is the largest cause of cancer-related mortality in
      both men and women. Despite some advances in the treatment of advanced non-small
      cell lung cancer (NSCLC), the introduction of third-generation cytotoxic agents
      (vinorelbine, gemcitabine, docetaxel, irinotecan, and paclitaxel) has not
      achieved a breakthrough in the dismal prognosis of this disease. Several meta
      analyses have proved the superiority of 2-drug chemotherapy and cisplatin-based
      chemotherapy, but no gold standard exists. This paper summarizes the clinical
      data of a new cytotoxic agent, pemetrexed, and its combination with platinums in
      the treatment of NSCLC. The addition of the vascular endothelial growth factor
      (VEGF) inhibitor (bevacizumab) or an EGFR-targeted drug (cetuximab) to
      pemetrexed/platinum in NSCLC, and the role of pemetrexed/platinum in adjuvant
      chemotherapy for early-stage NSCLC were also discussed in this paper.

PMID- 19839931
TI  - Pharmacological aspects of the enzastaurin-pemetrexed combination in non-small
      cell lung cancer (NSCLC).
AB  - Conventional regimens have limited impact against NSCLC. Current research is
      focusing on multiple pathways as potential targets, and this review describes
      pharmacological aspects underlying the combination of the PKCbeta-inhibitor
      enzastaurin with the multitargeted antifolate pemetrexed. Pemetrexed is commonly
      used, alone or combined with platinum compounds, in NSCLC treatment, and ongoing
      studies are evaluating its target, thymidylate synthase (TS), as predictor of
      drug activity. Enzastaurin is a biological targeted agent being actively
      investigated against different tumors as single agent or in combination. All the
      downstream events following PKCbeta inhibition by enzastaurin are not completely
      known, and assays to evaluate possible biomarkers, such as expression of PKC,
      VEGF and GSK3beta, in tissues and/or in blood samples, are being developed.
      Enzastaurin-pemetrexed combination was synergistic in preclinical models,
      including NSCLC cells, where enzastaurin reduced phosphoCdc25C, resulting in G2/M
      checkpoint abrogation, and Akt and GSK3beta; phosphorylation, favoring apoptosis
      induction in pemetrexed-damaged cells. Enzastaurin also significantly reduced
      VEGF secretion and pemetrexed-induced upregulation of TS expression, possibly via
      E2F-1 reduction, while the combination decreased TS activity. Similarly, the
      accumulation of deoxyuridine (a marker of TS inhibition) and the reduction of
      GSK3beta phosphorylation were detectable in clinical samples from a phase-Ib
      trial of pemetrexed-enzastaurin combination. In conclusion, the favorable
      toxicity profile and the multiple effects of enzastaurin on signaling pathways
      involved in cell cycle control, apoptosis and angiogenesis, as well as on
      proteins involved in pemetrexed activity, provide experimental basis for future
      studies on enzastaurin-pemetrexed combination and their possible pharmacodynamic
      markers in NSCLC patients.

PMID- 19839932
TI  - The role of pemetrexed combined with targeted agents for non-small cell lung
      cancer.
AB  - Pemetrexed is a novel third-generation multitargeted antifolate agent used in the
      first- and second-line treatment of unresectable pleural mesothelioma and
      advanced non-small cell lung cancer (NSCLC). Owing to its mild toxicity, this
      compound is a preferred partner in the multidrug regimens. In the last few
      decades, better understanding of molecular oncology and genetics has allowed for
      the development of an array of molecular targeted agents, many of which have been
      found active in NSCLC. It has been hoped that these compounds will disrupt tumor
      signaling pathways complementary to those targeted by chemotherapy. This review
      outlines the current preclinical and clinical studies using pemetrexed in
      combination with targeted agents in advanced NSCLC. Clinical experience with the
      use of these combinations is still limited and mostly includes phase I and II
      trials. These investigations have mainly focused on compounds previously shown to
      be active in NSCLC: anti-angiogenic agents (bevacizumab and small molecule
      tyrosine kinase inhibitors) and inhibitors of epidermal growth factor receptor
      (cetuximab and erlotinib). Preliminary results have shown the feasibility of
      these combinations and their promising activity but large phase III studies are
      warranted to verify the real value of this strategy. Combinations of pemetrexed
      with other targeted agents, such as mTOR inhibitors and compounds targeting
      proteasome are still at early stages of development.

PMID- 19839933
TI  - Cannabinoids and neurodegenerative diseases.
AB  - Although significant advances have taken place in recent years on our
      understanding of the molecular mechanisms of different neurodegenerative
      diseases, its translation into effective therapeutic treatments has not been as
      successful as could be expected. There is still a dramatic lack of curative
      treatments for the most frequent disorders and only symptomatic relief for many
      others. Under this perspective, the search for novel therapeutic approaches is
      demanding and significant attention and efforts have been directed to studying
      additional neurotransmission systems including the endocannabinoid system (ECS).
      The neuroprotective properties of exogenous as well as endogenous cannabinoids
      have been known for years and the underlying molecular mechanisms have been
      recently unveiled. As discussed later, antioxidative, antiglutamatergic and
      antiinflammatory effects are now recognized as derived from cannabinoid action
      and are known to be of common interest for many neurodegenerative processes.
      Thus, these characteristics make cannabinoids attractive candidates for the
      development of novel therapeutic strategies [1]. The present review will focus on
      the existing data regarding the possible usefulness of cannabinoid agents for the
      treatment of relevant neurological pathologies for our society such as
      Alzheimer's disease, multiple sclerosis, Huntington's disease and amyotrophic
      lateral sclerosis.

PMID- 19839934
TI  - Cannabinoids and Parkinson's disease.
AB  - Cannabinoid-based medicines have been proposed as clinically promising therapies
      in Parkinson's disease (PD), given the prominent modulatory function played by
      the cannabinoid signaling system in the basal ganglia. Supporting this
      pharmacological potential, the cannabinoid signaling system experiences a
      biphasic pattern of changes during the progression of PD. Thus, early and
      presymptomatic stages, characterized by neuronal malfunctioning but little
      evidence of neuronal death, are associated with desensitization/downregulation of
      CB(1) receptors. It was proposed that these losses may be part of the
      pathogenesis itself, since they can aggravate different cytotoxic insults which
      are controlled in part by cannabinoid signals, mainly excitotoxicity but also
      oxidative stress and glial activation. By contrast, intermediate and, in
      particular, advanced stages of parkinsonism characterized by a profound nigral
      degeneration and occurrence of major parkinsonian symptoms (e.g. bradykinesia),
      are associated with upregulatory responses of CB(1) receptors, possibly CB(2)
      receptors too, and the endocannabinoid ligands for both receptor types. This
      would explain the motor inhibition typical of this disease and the potential
      proposed for CB(1) receptor antagonists in attenuating the bradykinesia typical
      of PD. In addition, certain cannabinoid agonists have been proposed to serve as
      neuroprotective molecules in PD, given their well-demonstrated capability to
      reduce excitotoxicity, calcium influx, glial activation and, in particular,
      oxidative injury that cooperatively contribute to the degeneration of nigral
      neurons. However, the potential of cannabinoid-based medicines in PD have been
      still scarcely studied at the clinical level despite the existence of solid and
      promising preclinical evidence. Considering the relevance of these preclinical
      data, the need for finding treatments for motor symptoms that may be alternative
      to classic dopaminergic replacement therapy, and the lack of efficient
      neuroprotective strategies in PD, we believe it is of major interest to develop
      further studies that allow the promising expectations generated for these
      molecules to progress from the present preclinical evidence towards a real
      clinical application.

PMID- 19839936
TI  - The endocannabinoid system and the treatment of mood and anxiety disorders.
AB  - The central endocannabinoid system is a neuroactive lipid signalling system in
      the brain which acts to control neurotransmitter release. The expression patterns
      of this system throughout limbic regions of the brain ideally situate it to exert
      regulatory control over emotional behaviour, mood and stress responsivity. A
      growing body of evidence unequivocally demonstrates that deficits in
      endocannabinoid signalling may result in depressive and anxiogenic behavioral
      responses, while pharmacological augmentation of endocannabinoid signalling can
      produce both antidepressive and anxiolytic behavioral responses. The aim of this
      review is to summarize current knowledge of the role of the endocannabinoid
      system in the etiology and treatment of mood and anxiety disorders, such as
      depression, anxiety and post-traumatic stress disorder. Collectively, both
      clinical and preclinical data argue that cannabinoid receptor signalling may be a
      realistic target in the development of a novel class of agent for the
      pharmacotherapy of mood and anxiety disorders.

PMID- 19839935
TI  - Signal transduction via cannabinoid receptors.
AB  - The endocannabinoids anandamide and 2-arachidonoylglycerol are lipid mediators
      that signal via CB(1) and CB(2) cannabinoid receptors and Gi/o-proteins to
      inhibit adenylyl cyclase and stimulate mitogen-activated protein kinase. In the
      brain, CB(1) receptors interact with opioid receptors in close proximity, and
      these receptors may share G-proteins and effector systems. In the striatum, CB(1)
      receptors function in coordination with D(1) and D(2) dopamine receptors, and
      combined stimulation of CB(1)-D(2) receptor heteromeric complexes promotes a
      unique interaction to stimulate cAMP production. CB(1) receptors also trigger
      growth factor receptor signaling cascades in cells by engaging in cross-talk or
      interreceptor signal transmission with the receptor tyrosine kinase (RTK) family.
      Mechanisms for CB(1) receptor-RTK transactivation can include stimulation of
      signal transduction pathways regulated by second messengers such as phospholipase
      C, metalloprotease cleavage of membrane-bound precursor proteins such as
      epidermal growth factor which activate RTKs, RTK autophosphorylation, and
      recruitment of non-receptor tyrosine kinases. CB(1) and CB(2) receptors are
      expressed in peripheral tissues including liver and adipose tissue, and are
      induced in pathological conditions. Novel signal transduction resulting from
      endocannabinoid regulation of AMP-regulated kinase and peroxisome proliferator
      activated receptors have been discovered from studies of hepatocytes and
      adipocytes. It can be predicted that drug discovery of the future will be based
      upon these novel signal transduction mechanisms for endocannabinoid mediators.

PMID- 19839938
TI  - Imatinib mesylate (Gleevec): targeted therapy against cancer with immune
      properties.
AB  - The treatment against cancer is being flooded by targeted therapies. Imatinib
      mesylate (Gleevec) was the first molecule to provide the proof of principle that
      targeting an aberrant tyrosine kinase responsible for the uncontrolled cell cycle
      progression allows for the eradication of tumors. The ideal targeted therapy
      should eliminate the molecular event responsible for the disease, an oncogenic
      product such as c-KIT, ABL/BCR and PDGFRa in the case of Gleevec. Two issues
      related to this conceptual advance are raised in clinical practice. First, these
      therapies might target additional pathways generating side effects. Secondly, non
      tumoral cells bearing the molecular target might respond and induce additional
      biological outcomes. This review will summarize the by-stander immune modulations
      promoted by the paradigmatic compound Gleevec, leading to unexpected new
      therapeutic indications.

PMID- 19839940
TI  - New biochemical approaches towards understanding the Parkinson's disease
      associated kinase, LRRK2.
AB  - Some 5 years ago, it was first discovered that mutations in the gene encoding
      LRRK2 (leucine-rich repeat protein kinase 2) are tightly linked with a subset of
      familial PD (Parkinson's disease). Before this genetic association, LRRK2 had
      never been investigated biochemically. Now it is of utmost importance to
      establish whether LRRK2 is a bona fide kinase in vitro and in vivo and to
      understand how mutations of LRRK2 lead to the specific loss of dopaminergic
      neurons in the substantia nigra to cause PD. In spite of tremendous efforts in
      the research community, there is no consensus with regard to the magnitude of the
      enzymatic activity of LRRK2 mutant forms that segregate with PD owing, in part,
      to the lack of a highly sensitive kinase assay system, and it is still unclear
      whether an abnormal increase in kinase activity is responsible for LRRK2
      associated PD. As described in this issue of the Biochemical Journal, Nichols et
      al.. have developed an extensive set of molecular tools, including an optimized
      peptide substrate for determining in vitro kinase activity of LRRK2, a set of
      kinase inhibitors that can be used to explore LRRK2 substrate specificity and
      biology, a much-needed murine-specific antibody for immunoprecipation, and
      efficient gene-silencing approaches. In the present commentary, we discuss some
      of the components of this new LRRK2 biochemical toolbox and how they can be used
      to better understand this enigmatic kinase.

PMID- 19839939
TI  - Animal models for Alzheimer's disease and frontotemporal dementia: a perspective.
AB  - In dementia research, animal models have become indispensable tools. They not
      only model aspects of the human condition, but also simulate processes that occur
      in humans and hence provide insight into how disease is initiated and propagated.
      The present review discusses two prominent human neurodegenerative disorders,
      Alzheimer's disease and frontotemporal dementia. It discusses what we would like
      to model in animals and highlights some of the more recent achievements using
      species as diverse as mice, fish, flies and worms. Advances in imaging and
      therapy are explored. We also discuss some anticipated new models and
      developments. These will reveal how key players in the pathogenesis of
      Alzheimer's disease and frontotemporal dementia, such as the peptide Abeta
      (amyloid beta) and the protein tau, cause neuronal dysfunction and eventually,
      neuronal demise. Understanding these processes fully will lead to early diagnosis
      and therapy.

PMID- 19839941
TI  - Nordic guidelines for neuraxial blocks in disturbed haemostasis from the
      Scandinavian Society of Anaesthesiology and Intensive Care Medicine.
AB  - BACKGROUND: Central neuraxial blocks (CNBs) for surgery and analgesia are an
      important part of anaesthesia practice in the Nordic countries. More active
      thromboprophylaxis with potent antihaemostatic drugs has increased the risk of
      bleeding into the spinal canal. National guidelines for minimizing this risk in
      patients who benefit from such blocks vary in their recommendations for safe
      practice. METHODS: The Scandinavian Society of Anaesthesiology and Intensive Care
      Medicine (SSAI) appointed a task force of experts to establish a Nordic consensus
      on recommendations for best clinical practice in providing effective and safe
      CNBs in patients with an increased risk of bleeding. We performed a literature
      search and expert evaluation of evidence for (1) the possible benefits of CNBs on
      the outcome of anaesthesia and surgery, for (2) risks of spinal bleeding from
      hereditary and acquired bleeding disorders and antihaemostatic drugs used in
      surgical patients for thromboprophylaxis, for (3) risk evaluation in published
      case reports, and for (4) recommendations in published national guidelines.
      Proposals from the taskforce were available for feedback on the SSAI web-page
      during the summer of 2008. RESULTS: Neuraxial blocks can improve comfort and
      reduce morbidity (strong evidence) and mortality (moderate evidence) after
      surgical procedures. Haemostatic disorders, antihaemostatic drugs, anatomical
      abnormalities of the spine and spinal blood vessels, elderly patients, and renal
      and hepatic impairment are risk factors for spinal bleeding (strong evidence).
      Published national guidelines are mainly based on experts' opinions (weak
      evidence). The task force reached a consensus on Nordic guidelines, mainly based
      on our experts' opinions, but we acknowledge different practices in
      heparinization during vascular surgery and peri-operative administration of non
      steroidal anti-inflammatory drugs during neuraxial blocks. CONCLUSIONS: Experts
      from the five Nordic countries offer consensus recommendations for safe clinical
      practice of neuraxial blocks and how to minimize the risks of serious
      complications from spinal bleeding. A brief version of the recommendations is
      available on http://www.ssai.info.

PMID- 19839937
TI  - The endocannabinoid system and pain.
AB  - The therapeutic potential of cannabinoids has been the topic of extensive
      investigation following the discovery of cannabinoid receptors and their
      endogenous ligands. Cannabinoid receptors and their endogenous ligands are
      present at supraspinal, spinal and peripheral levels. Cannabinoids suppress
      behavioral responses to noxious stimulation and suppress nociceptive processing
      through activation of cannabinoid CB(1) and CB(2) receptor subtypes.
      Endocannabinoids, the brain's own cannabis-like substances, share the same
      molecular target as Delta(9)-tetrahydrocannabinol, the main psychoactive
      component in cannabis. Endocannabinoids serve as synaptic circuit breakers and
      regulate multiple physiological and pathological conditions, e.g. regulation of
      food intake, immunomodulation, inflammation, analgesia, cancer, addictive
      behavior, epilepsy and others. This review will focus on uncovering the roles of
      anandamide and 2-arachidonoylglycerol, the two best characterized
      endocannabinoids identified to date, in controlling nociceptive responding. The
      roles of anandamide and 2-arachidonoylglycerol, released under physiological
      conditions, in modulating nociceptive responding at different levels of the
      neuraxis will be emphasized in this review. Effects of modulation of
      endocannabinoid levels through inhibition of endocannabinoid hydrolysis and
      uptake is also compared with effects of exogenous administration of synthetic
      endocannabinoids in acute, inflammatory and neuropathic pain models. Finally, the
      therapeutic potential of the endocannabinoid signaling system is discussed in the
      context of identifying novel pharmacotherapies for the treatment of pain.

PMID- 19839942
TI  - Circadian rhythm of stroke onset during the month of Ramadan.
AB  - BACKGROUND AND PURPOSE: The onset of acute stroke exhibits a circadian pattern
      occurring more frequently in late morning hours. The objective of this study was
      to investigate the diurnal pattern of stroke during the month of Ramadan.
      PATIENTS AND METHODS: We studied consecutive stroke patients 1 month before
      Ramadan (BR) and during Ramadan (DR) over two successive years 2007 and 2008. The
      age, gender, risk factor profiles were analyzed. The National Institute of Health
      and Stroke Scale Score (NIHSS) was used for clinical assessment at admission. The
      exact time of stroke onset in both groups was obtained. RESULTS: A total of 507
      patients were studied: 245 patients in the DR group and 262 patients in the BR
      group. The age distribution of patients was not significantly different between
      the two groups. There was no statistically significant difference in the sex
      ratio, risk factors, and NIHSS score between the two groups (P > 0.05). The
      higher frequency of stroke onset time in the BR group was in the time between
      6:00 a.m. and noon; whereas the frequency was higher between noon and 6:00 p.m.
      in the DR group. CONCLUSION: A significant shift of the circadian pattern of
      stroke onset time from the period between 6:00 a.m. and noon to that between noon
      and 6:00 pm has been found during the month of Ramadan.

PMID- 19839943
TI  - Assessment of post-stroke extrapersonal neglect using a three-dimensional
      immersive virtual street crossing program.
AB  - OBJECTIVE: To investigate the potential of our newly developed three-dimensional
      immersive virtual reality (VR) program modeled on a real street crossing as an
      assessment tool for extrapersonal neglect in stroke patients. METHODS: Thirty-two
      patients with right-hemispheric stroke (neglect group, 16; non-neglect group, 16)
      were enrolled. The deviation angle, reaction time, left-to-right reaction time
      ratio, visual and auditory cue rates, and failure rate were evaluated during
      missions to keep a virtual avatar safe from a traffic accident in the VR program.
      The line bisection test and letter cancellation test were also evaluated.
      RESULTS: The deviation angle, left-to-right reaction time ratio, left visual and
      auditory cue rates and left failure rate in the VR program showed significant
      differences between the two groups (P < 0.05). Depending on the direction of
      approach of the virtual car, the left parameters were significantly higher than
      the right parameters in the neglect group (P < 0.05). In the neglect group, the
      line bisection test correlated significantly with the deviation angle (P < 0.05).
      None of the other virtual reality parameters significantly correlated with the
      paper and pencil tests. CONCLUSION: Post-stroke neglect in the extrapersonal
      space can be easily and safely detected and measured using our three-dimensional
      immersive virtual street crossing program.

PMID- 19839945
TI  - Persistent sensory dysfunction in pain-free herniotomy.
AB  - BACKGROUND: Persistent post-herniotomy pain may be a neuropathic pain state based
      on the finding of a persistent sensory dysfunction. However, detailed information
      on the normal distribution of sensory function in pain-free post-herniotomy
      patients hinders identification of exact pathogenic mechanisms. Therefore, we
      aimed to establish normative data on sensory function in pain-free patients >1
      year after a groin herniotomy. METHODS: Sensory thresholds were assessed in 40
      pain-free patients by a standardized quantitative sensory testing (QST).
      Secondary endpoints included comparison of sensory function between the operated
      and the naive side, and correlation between sensory function modalities. RESULTS:
      QST showed that on the operated side, thermal data were normally distributed, but
      mechanical pressure and pinch thresholds were normalized only after log
      transformation, and cold pain and pressure tolerance could not be normalized.
      Comparison of QST results revealed significant (P<0.01) cutaneous
      hypoesthesia/hyperalgesia, but also significant pressure hyperalgesia (P<0.01)
      and decreased pressure tolerance (P=0.02) on the operated vs. the naive side.
      Wind-up was seen in 6 (15%) but with a low pain intensity. CONCLUSION: Persistent
      sensory dysfunction is common in pain-free post-herniotomy patients. Future
      studies of sensory function in persistent post-herniotomy pain should compare the
      findings to the present data in order to characterize individual patients and
      potentially identify subgroups, which may aid in allocation of patients to
      pharmacological or surgical treatment.

PMID- 19839944
TI  - Correlation and agreement between the bispectral index vs. state entropy during
      hypothermic cardio-pulmonary bypass.
AB  - BACKGROUND: The bispectral index (BIS) and spectral entropy enable monitoring the
      depth of anaesthesia. Mild hypothermia has been shown to affect the ability of
      electroencephalography monitors to reflect the anaesthetic drug effect. The
      purpose of this study was to investigate the effect of hypothermia during a
      cardio-pulmonary bypass on the correlation and agreement between the BIS and
      entropy variables compared with normothermic conditions. METHODS: This
      prospective clinical study included coronary artery bypass grafting patients
      (n=25) evaluating correlation and agreement (Bland-Altman analysis) between the
      BIS and both spectral and response entropy during a hypothermic cardio-pulmonary
      bypass (31-34 degrees C) compared with nomothermic conditions (34-37.5 degrees
      C). Anaesthesia was maintained with propofol and sufentanil and adjusted
      clinically, while the anaesthetist was blinded to the monitors. RESULTS: The BIS
      and entropy values decreased during cooling (P<0.05), but the decrease was more
      pronounced for entropy variables compared with BIS (P<0.05). The correlation
      coefficients (bias+/-SD; percentage error) between the BIS vs. spectral state
      entropy and response entropy were r(2)=0.56 (1+/-11; 42%) and r(2)=0.58 (-2+/-11;
      43%) under normothermic conditions, and r(2)=0.17 (10+/-12; 77%) and r(2)=0.18
      (9+/-11; 68%) under hypothermic conditions, respectively. Bias was significantly
      increased under hypothermic conditions (P<0.001 vs. normothermia). CONCLUSION:
      Acceptable agreement was observed between the BIS and entropy variables under
      normothermic but not under hypothermic conditions. The BIS and entropy variables
      may therefore not be interchangeable during a hypothermic cardio-pulmonary
      bypass.

PMID- 19839946
TI  - Pharmacokinetics after an intravenous single dose of the opioid ketobemidone in
      children.
AB  - BACKGROUND: Ketobemidone is often used as an alternative to morphine in children
      in the Scandinavian countries. The aim of this clinical trial was to explore the
      pharmacokinetics of ketobemidone in children because these properties have not
      been reported previously. METHODS: Thirty children, newborn to 10 years,
      scheduled for elective surgery were included in the trial. Ketobemidone
      hydrochloride was administered as a single intravenous bolus dose and
      ketobemidone and norketobemidone concentrations were measured by LC-MS over 8 h.
      Pharmacokinetic parameters were determined using compartmental methods. RESULTS:
      Six children were excluded from pharmacokinetic analysis because of incomplete
      blood sampling. The values of ketobemidone clearance (l/h/kg) given as median
      (range) were 0.84 (0.29-3.0) in Group A (0-90 days), 0.89 (0.55-1.35) in Group B
      (1-2.5 years) and 0.74 (0.50-0.99) in Group C (7-10 years). The corresponding
      values for apparent volume of distribution (l/kg) were 4.4 (3.7-6.9) (Group A),
      2.6 (2.0-5.6) (Group B) and 3.9 (2.7-5.0 (Group C), and for elimination half-life
      (h) 3.0 (1.4-8.9) (Group A), 2.0 (1.2-4.7) (Group B) and 3.7 (2.4-6.9) (Group C),
      respectively. In the two neonates the elimination half-life was almost 9 h. The
      metabolite norketobemidone did not reach levels above the limit of quantification
      (0.07 ng/ml) in any of the patients. CONCLUSION: The pharmacokinetic parameters
      of ketobemidone in children older than 1 month appear to be similar to those in
      adults. Because of the large interindividual variability of the pharmacokinetics
      in neonates, further studies especially in this age group are warranted.

PMID- 19839947
TI  - Knowledge of residual curarization: an Italian survey.
AB  - BACKGROUND: The use of neuromuscular blocking agents (NMBAs) is widespread in
      anesthetic practice; little is known about the current use of these drugs in
      Italy. This survey was conducted to obtain information about the most commonly
      used clinical tests and the train-of-four (TOF) ratios that are considered as
      being reliable for assessing recovery from neuromuscular blockade at the end of
      anesthesia and the estimated occurrence rates of post-operative paralysis in
      Italian hospitals. METHODS: The questionnaire was given to Italian
      anesthesiologists attending the 62nd National Congress of the Italian Society of
      Anesthesia, Analgesia and Intensive Therapy. Collected data were stratified by
      age and the total number of surgical procedures performed in the hospitals
      concerned. RESULTS: Seven hundred and fifty-four correctly compiled
      questionnaires were collected (response rate 88.7%). Seventy three percent of the
      respondents only used clinical tests for monitoring the level of neuromuscular
      blockade. The main clinical tests cited for the evaluation of residual paralysis
      were keeping the head lifted up for 5 s, protruding the tongue and opening the
      eyes. TOF was used by 35% of the respondents on a routine basis. Only 24% of the
      interviewed anesthesiologists reported that before extubation, a TOF ratio of at
      least 0.9 should be reached. CONCLUSIONS: Most Italian anesthetists assess the
      recovery from neuromuscular blockade only by clinical signs. There is poor
      awareness about the inability of such techniques to indicate even a significant
      amount of residual neuromuscular block. A more extensive use of quantitative
      instrumental monitoring is required for the more rational use of NMBAs.

PMID- 19839948
TI  - Neurolytic phenol blockade of the obturator nerve for severe adductor spasticity.
AB  - BACKGROUND: In this study, we present the 3-month follow-up results of a
      retrospective analysis of obturator nerve (ON) phenol neurolysis performed
      between 2000 and 2007 in patients with adductor spasticity. METHODS: The study
      was performed by retrospective investigation of the clinical follow-up results of
      80 ON phenol treatments in 62 patients. Neurolysis using 5-10 ml 6% phenol was
      applied with the guidance of fluoroscopy and a peripheral nerve stimulator. Pain,
      spasticity and hygiene were evaluated and the hip abduction range of motion (ROM)
      was measured at the end of the first week and in the first, second and third
      months following the intervention. RESULTS: The visual analogue scale scores
      decreased significantly in the first week, first month and the second month, but
      reached their initial values in the third month. A drastic increase in the ROM
      values was shown in hip abduction in the first week, first month and second
      month. An increase in the Ashworth Scale values was observed in the second and
      third months, but they did not reach their initial values. The hygiene score
      decreased drastically in the first week and the first and second months, but
      worsened in the third month. The success rate in nerve localization during ON
      neurolysis was 100%. CONCLUSION: ON phenol blockade with fluoroscopy and
      peripheral nerve stimulator guidance in patients with adductor spasticity led to
      a decrease in spasticity and pain with an increase in the ROM of the hip and
      better hygiene with an efficacy lasting for about 3 months.

PMID- 19839949
TI  - Unilateral paravertebral block: an alternative to conventional spinal anaesthesia
      for inguinal hernia repair.
AB  - BACKGROUND: Inguinal herniorrhaphy can be successfully performed using general,
      regional or local anaesthesia. Paravertebral block (PVB) has been used for
      unilateral procedures such as thoracotomy, breast surgery, chest wall trauma,
      hernia repair or renal surgery. METHODS: We compared unilateral lumbar PVB with
      conventional spinal anaesthesia (SA) in 60 consenting ASA I and II males aged 18
      65 years, scheduled for unilateral inguinal hernia repair. Patients were randomly
      assigned into two groups, P (n=30) or S (n=30) to receive either PVB or SA,
      respectively. Two patients (7%) in group P had to be converted to general
      anaesthesia due to block failure. During surgery, patients of both groups
      received intravenous infusion of propofol titrated to light sedation. RESULTS:
      The time to first post-operative analgesic requirement (primary outcome measure)
      as 342 +/- 73 min in group P and 222 +/- 22 min in group S (P<0.0001). Time to
      ambulation was 234 +/- 111 min in group P and 361 +/- 32 min in group S
      (P<0.0001). Urinary retention requiring catheterization were found in zero (0%)
      patients in group P compared with five (16%) in group S (P=0.024). CONCLUSION: It
      can be concluded that unilateral PVB is more efficacious than conventional SA in
      terms of prolonging post-operative analgesia and reducing morbidities in patients
      undergoing elective unilateral inguinal hernia repair.

PMID- 19839950
TI  - Xenon and isoflurane improved biventricular function during right ventricular
      ischemia and reperfusion.
AB  - BACKGROUND: Although anesthetics have some cardioprotective properties, these
      benefits are often counterbalanced by their negative inotropic effects. Xenon, on
      the other hand, does not influence myocardial contractility. Thus, xenon may be a
      superior treatment for the maintenance of global hemodynamics, especially during
      right ventricular ischemia, which is generally characterized by a high acute
      complication rate. METHODS: The effects of 70 vol% xenon and 0.9 vol% isoflurane
      on biventricular function were assessed in a porcine model (n=36) using the
      conductance catheter technique, and the expression of the type B natriuretic
      peptide (BNP) gene was measured. The animals underwent 90 min of right
      ventricular ischemia followed by 120 min of reperfusion. A barbiturate
      anesthetized group was included as a control. RESULTS: Cardiac output was
      compromised in unprotected animals during ischemia by 33+/-18% and during
      reperfusion by 53+/-17%. This was mainly due to impaired contractility in the
      left ventricle (LV) and increased stiffness. Isoflurane attenuated the increase
      in stiffness and resulted in a higher preload. In contrast, xenon increased the
      right ventricular afterload, which was compensated by an increase in
      contractility. Its effects on diastolic function were less pronounced.
      Upregulation of BNP mRNA expression was impeded in the remote area of the LV by
      both isoflurane and xenon. CONCLUSIONS: Xenon and isoflurane demonstrated
      equipotent effects in preventing the hemodynamic compromise that is induced by
      right ventricular ischemia and reperfusion, although they acted through somewhat
      differential inotropic and vasodilatory effects.

PMID- 19839951
TI  - Real-time ultrasound-guided spinal anesthesia in patients with a challenging
      spinal anatomy: two case reports.
AB  - Spinal anesthesia may be challenging in patients with poorly palpable surface
      landmarks or abnormal spinal anatomy. Pre-procedural ultrasound imaging of the
      lumbar spine can help by providing additional anatomical information, thus
      permitting a more accurate estimation of the appropriate needle insertion site
      and trajectory. However, actual needle insertion in the pre-puncture ultrasound
      assisted technique remains a 'blind' procedure. We describe two patients with an
      abnormal spinal anatomy in whom ultrasound-assisted spinal anesthesia was
      unsuccessful. Successful dural puncture was subsequently achieved using a
      technique of real-time ultrasound-guided spinal anesthesia. This may be a useful
      option in patients in whom landmark-guided and ultrasound-assisted techniques
      have failed.

PMID- 19839952
TI  - Validation and clinical feasibility of nitrogen washin/washout functional
      residual capacity measurements in children.
AB  - BACKGROUND: The functional residual capacity (FRC) is an important parameter in
      pediatric respiratory monitoring but it is difficult to assess in the clinical
      setting. We have introduced a modified N(2) washout method utilizing a change of
      F(I)O(2) of 0.1 for FRC measurement in adult respiratory monitoring. This study
      validated the algorithm in a pediatric lung model and investigated the stability
      and feasibility in a pediatric peri-operative and intensive care setting.
      METHODS: The lung model was ventilated in combinations of ventilatory modes,
      CO(2) production, model FRC and respiratory rates. Sixteen children from 10 days
      to 5 years were studied peri-operatively with controlled ventilation using a
      Mapleson D system and in the intensive care unit using a Servo-i ventilator in a
      supported spontaneous mode. FRC was measured during stable metabolic, respiratory
      and circulatory periods at positive end expiratory pressure of 3-4 and 7-8
      cmH(2)O. RESULTS: In the model and in the clinical setting, we found an excellent
      agreement between washout and washin measurements of FRC as well as acceptable
      coefficients of repeatability. CONCLUSION: FRC was satisfactorily measured by a
      modified N(2) algorithm and may be included as a monitoring variable in pediatric
      respiratory care. Pediatric FRC monitoring demands strictly stable conditions as
      measurements are performed close to the limits of the monitor's specifications.

PMID- 19839953
TI  - Treatment of acute pulmonary haemorrhage in extremely preterm infants with
      recombinant activated factor VII.

PMID- 19839954
TI  - Meta-analysis of blood pressure tracking from childhood to adulthood and
      implications for the design of intervention trials.
AB  - AIM: Blood pressure (BP) is related with cardiovascular disease. BP tracking in
      childhood and its implication for intervention trials are unknown. METHODS: A
      systematic review and meta-analysis were conducted to estimate BP tracking.
      RESULTS: In 29 independent studies on 27,820 subjects, follow-up length and
      baseline age were associated with systolic BP tracking (both p < 0.05), while
      gender, BP measurement method and study place were not (p = 0.215, p = 0.185 and
      p = 0.391). The overall adjusted systolic BP correlation coefficient was 0.44
      between 10 and 11 years and decreased to 0.37 between 10 and 20 years. Comparison
      of BP changes before and after intervention need a 26% increased sample size for
      a 10-year follow-up of 10 year olds, while trials comparing BP values at study
      end only require smaller sample sizes. CONCLUSION: Blood pressure tracking from
      childhood to adulthood affects trials assessing long-term effects on BP and was
      low-to-moderate. Therefore, regular BP controls are also needed in children with
      normal BP measurements possibly identifying hypertensive children earlier. A
      slight short-term intervention effect on BP may not have any long-term effects
      because of low BP tracking and its decrease by age.

PMID- 19839955
TI  - Helicobacter pylori infection in children: population-based age-specific
      prevalence and risk factors in a developing country.
AB  - AIM: We estimated the prevalence, age of acquisition and risk factors for
      Helicobacter pylori (H. pylori) seroprevalence in children aged 1-15 years.
      METHODS: Exposure was assessed using ELISA. Parents responded to a questionnaire
      regarding number of individuals sharing house, rooms, water source, latrines,
      housing and assessment of socioeconomic status (SES) by Hollingshead Index.
      RESULTS: Serum of 1976 children was tested. Helicobacter pylori seropositivity in
      children aged 11-15 years was 53.5% (OR: 2.0, 95% CI: 1.58-2.5). It increased
      with moderate crowding index (CRI) of 2-4 to 45.9% (OR: 1.23, 95% CI: 0.92-1.63)
      and to 51.2% with CRI >4 (OR: 1.52, 95% CI: 1.12-2.06). In middle SES,
      seropositivity was 50.5% (331/655) (OR: 1.7, 95% CI: 1.29-2.35), whereas in lower
      SES, it was 47.1% (500/1062) (OR: 1.5, 95% CI: 1.1-2.0). Multivariate analysis
      showed that Helicobacter pylori seroprevalence was high in children aged 6-10 and
      11-15 years (OR: 1.5, 95% CI: 1.2-1.9 and OR: 1.9, 95% CI: 1.56-2.47
      respectively), in lower-middle SES (OR: 1.6, 95% CI: 1.2-2.1 and OR: 1.5, 95% CI:
      1.10-2.0 respectively) and in uneducated fathers (OR: 1.58, 95% CI: 1.27-1.95).
      CONCLUSION: Helicobacter pylori seropositivity increases with age, in low-middle
      SES and is related to father's educational status. Reducing H. pylori
      seroprevalence will require improvement in sanitary conditions and educational
      status of the population.

PMID- 19839956
TI  - International comparison of blood pressure and BMI values in schoolchildren aged
      11-16 years.
AB  - AIMS: This study comprised part of a larger cross-sectional survey performed in
      Hungary in the period 2005-2006, which was designed first to reveal the
      representative age-, gender- and height-specific percentile values for the
      systolic blood pressure (SBP) and the diastolic blood pressure (DBP) in Hungarian
      children aged 11-16 years. The second aim was to determine the prevalence of
      overweight and obesity. METHODS: Analyses were performed on 14,290 Hungarian
      children aged 11-16 years. All blood pressure (BP) measurements were made with a
      validated, automated, digital device. The criteria recommended by international
      guidelines were used. RESULTS: The prevalence of overweight and obesity among the
      Hungarian children was found to be 23.4% (3347 adolescents; International Obesity
      Task Force criteria). Previous studies have reported that the strongest
      correlation is observed between the BP values and weight, and our results are in
      accordance with this. CONCLUSIONS: Regional differences in morphometry (different
      prevalences of overweight and obesity) and the genetic background, disparate
      eating habits and other cultural factors may account for the differences in BP
      levels during childhood. As the prevalence of overweight and obesity is
      increasing worldwide, it is important that countries carefully monitor the weight
      and BP status of their children and adolescents.

PMID- 19839957
TI  - Maturational changes in the feeding behaviour of infants - a comparison between
      breast-feeding and bottle-feeding.
AB  - AIM: To obtain a better understanding of the changes in feeding behaviour from 1
      to 6 months of age. By comparing breast- and bottle-feeding, we intended to
      clarify the difference in longitudinal sucking performance. METHODS: Sucking
      variables were consecutively measured for 16 breast-fed and eight bottle-fed
      infants at 1, 3 and 6 months of age. RESULTS: For breast-feeding, number of sucks
      per burst (17.8 +/- 8.8, 23.8 +/- 8.3 and 32.4 +/- 15.3 times), sucking burst
      duration (11.2 +/- 6.1, 14.7 +/- 8.0 and 17.9 +/- 8.8 sec) and number of sucking
      bursts per feed (33.9 +/- 13.9, 28.0 +/- 18.2 and 18.6 +/- 12.8 times) at 1, 3
      and 6 months of age respectively showed significant differences between 1 and 6
      months of age (p < 0.05). The sucking pressure and total number of sucks per feed
      did not differ among different ages. Bottle-feeding resulted in longer sucking
      bursts and more sucks per burst compared with breast-feeding in each month (p <
      0.05). CONCLUSION: The increase in the amount of ingested milk with maturation
      resulted from an increase in bolus volume per minute as well as the higher number
      of sucks continuously for both breast- and bottle-fed infants.

PMID- 19839958
TI  - Management of isolated rectal bleeding in newborn infants: comparison of two time
      periods.
AB  - AIM: To demonstrate the differences in treatment of isolated rectal bleeding
      (IRB) by comparing two study time period groups and to evaluate whether decreased
      treatment intensity increased complications during the follow-up period. METHODS:
      Retrospective recording of medical charts of 307 neonates with IRB during two
      time periods. RESULTS: The rate of IRB in both period groups was similar among
      term and near-term infants, but significantly lower among preterm infants in the
      later period study group. The rate of breast milk feeding among preterm infants
      increased significantly in the later compared with the early group. Duration of
      antibiotic treatments and feeding cessation was significantly shortened in the
      late period study as compared with the early period. The rates of recurrent
      episodes of IRB among preterm infants were similar in the early and late period
      groups. No infant developed necrotizing enterocolitis within the episode of
      isolated rectal bleeding. CONCLUSIONS: Decreased treatment duration to 1 day of
      nil per os and 2 days of antibiotics was not associated with increased rates of
      deterioration to severe clinical conditions, nor to recurrent episodes of
      isolated rectal bleeding.

PMID- 19839959
TI  - A case of glycogen storage disease type Ib presenting with prolonged neonatal
      hypoglycaemia and minimal metabolic abnormalities.

PMID- 19839960
TI  - A 3-year longitudinal analysis of changes in fitness, physical activity, fatness
      and screen time.
AB  - AIM: To analyse whether changes in physical activity index (PAI), screen time
      (ST: television, computer) and body mass index (BMI) made a contribution to
      longitudinal changes in fitness of children and adolescents. Additionally, we
      analysed the interaction between baseline fitness level and changes in fitness.
      METHODS: This is a 3-year longitudinal study of 345 high school students aged 11
      19 years. Students performed curl-ups, push-ups and 20-m shuttle run tests from
      Fitnessgram. PA and ST were evaluated using a standard questionnaire.
      Standardized scores of fitness tests were summed. Changes over time were
      calculated as Delta(1) (2007 minus 2006), Delta(2) (2008 minus 2007) and Delta(3)
      (2008 minus 2006). RESULTS: Changes in PAI were positively and independently
      associated with changes in fitness in Delta(1), Delta(2) and Delta(3). Changes in
      BMI were negatively associated with changes in fitness in Delta(3). Participants
      highly fit at baseline were those who showed positive changes in PAI over
      Delta(3), decreased changes in ST and had the lowest increase in BMI over 3 years
      compared with those low-fit at baseline. CONCLUSIONS: Changes in BMI were
      associated with changes in fitness over 3 years. However, changes in PAI were the
      best predictor for changes in fitness in each year and over the 3 years of
      evaluation in youth.

PMID- 19839961
TI  - Adolescent sexual behaviour and public health: the religion versus science
      dichotomy.

PMID- 19839962
TI  - Postnatal methadone withdrawal syndrome: hair analysis for detecting chronic
      exposure.

PMID- 19839963
TI  - Treatment of neonatal abstinence syndrome with clonidine and chloral hydrate.
AB  - AIM: The objective of this retrospective study is to compare the medical
      treatment of neonatal narcotic abstinence syndrome with clonidine and chloral
      hydrate with the commonly used combination therapy of morphine and phenobarbital.
      METHODS: From 1998 to 2008, a total of 133 newborns suffering from neonatal
      narcotic abstinence syndrome were treated at our clinic. All of these patients
      were born to mothers who had received methadone substitution for drug addiction
      during the course of pregnancy. RESULTS: Twenty-nine patients received clonidine
      and chloral hydrate, and 64 patients were treated with morphine and phenobarbital
      for abstinence syndrome. The duration of treatment was significantly shorter in
      the clonidine/chloral hydrate group (median: 14 days vs. 35 days).
      Correspondingly, the period of hospitalization was also considerably shorter in
      the clonidine/chloral hydrate group (median: 32 days vs. 44 days). In addition,
      patients in the clonidine/chloral hydrate group exhibited markedly reduced
      withdrawal symptoms. CONCLUSION: This study suggests that a treatment of neonatal
      abstinence syndrome with clonidine in omission of opiates is possible without
      causing short-term adverse cardiovascular effects. Considering the retrospective
      design of the study, controlled and prospective trials are needed.

PMID- 19839964
TI  - Cannabis and crime: findings from a longitudinal study.
AB  - AIM: To examine the association between cannabis use during adolescence and young
      adulthood, and subsequent criminal charges. METHODS: Data were obtained from the
      Young in Norway Longitudinal Study. A population-based sample (n = 1353) was
      followed from 13 to 27 years of age. Data were gathered on cannabis use, alcohol
      consumption and alcohol problems, and use of other illegal substances such as
      amphetamines, cocaine and opiates. In addition, extensive information on socio
      demographic, family and personal factors was collected. This data set was linked
      to individual-level information from official Norwegian crime statistics.
      FINDINGS: We found robust associations between cannabis use and later registered
      criminal charges, both in adolescence and in young adulthood. These associations
      were adjusted for a range of confounding factors, such as family socio-economic
      background, parental support and monitoring, educational achievement and career,
      previous criminal charges, conduct problems and history of cohabitation and
      marriage. In separate models, we controlled for alcohol measures and for use of
      other illegal substances. After adjustment, we still found strong associations
      between cannabis use and later criminal charges. However, when eliminating all
      types of drug-specific charges from our models, we no longer observed any
      significant association with cannabis use. CONCLUSIONS: The study suggests that
      cannabis use in adolescence and early adulthood may be associated with subsequent
      involvement in criminal activity. However, the bulk of this involvement seems to
      be related to various types of drug-specific crime. Thus, the association seems
      to rest on the fact that use, possession and distribution of drugs such as
      cannabis is illegal. The study strengthens concerns about the laws relating to
      the use, possession and distribution of cannabis.

PMID- 19839965
TI  - Policy options for alcohol price regulation: the importance of modelling
      population heterogeneity.
AB  - Context and aims Internationally, the repertoire of alcohol pricing policies has
      expanded to include targeted taxation, inflation-linked taxation, taxation based
      on alcohol-by-volume (ABV), minimum pricing policies (general or targeted), bans
      of below-cost selling and restricting price-based promotions. Policy makers
      clearly need to consider how options compare in reducing harms at the population
      level, but are also required to demonstrate proportionality of their actions,
      which necessitates a detailed understanding of policy effects on different
      population subgroups. This paper presents selected findings from a policy
      appraisal for the UK government and discusses the importance of accounting for
      population heterogeneity in such analyses. Method We have built a causal,
      deterministic, epidemiological model which takes account of differential
      preferences by population subgroups defined by age, gender and level of drinking
      (moderate, hazardous, harmful). We consider purchasing preferences in terms of
      the types and volumes of alcoholic beverages, prices paid and the balance between
      bars, clubs and restaurants as opposed to supermarkets and off-licenses. Results
      Age, sex and level of drinking fundamentally affect beverage preferences,
      drinking location, prices paid, price sensitivity and tendency to substitute for
      other beverage types. Pricing policies vary in their impact on different product
      types, price points and venues, thus having distinctly different effects on
      subgroups. Because population subgroups also have substantially different risk
      profiles for harms, policies are differentially effective in reducing health,
      crime, work-place absence and unemployment harms. Conclusion Policy appraisals
      must account for population heterogeneity and complexity if resulting
      interventions are to be well considered, proportionate, effective and cost
      effective.

PMID- 19839966
TI  - Randomized controlled trial of dexamphetamine maintenance for the treatment of
      methamphetamine dependence.
AB  - AIM: To investigate the safety and efficacy of once-daily supervised oral
      administration of sustained-release dexamphetamine in people dependent on
      methamphetamine. DESIGN: Randomized, double-blind, placebo-controlled trial.
      PARTICIPANTS: Forty-nine methamphetamine-dependent drug users from Drug and
      Alcohol Services South Australia (DASSA) clinics. INTERVENTION: Participants were
      assigned randomly to receive up to 110 mg/day sustained-release dexamphetamine (n
      = 23) or placebo (n = 26) for a maximum of 12 weeks, with gradual reduction of
      the study medication over an additional 4 weeks. Medication was taken daily under
      pharmacist supervision. MEASUREMENTS: Primary outcome measures included treatment
      retention, measures of methamphetamine consumption (self-report and hair
      analysis), degree of methamphetamine dependence and severity of methamphetamine
      withdrawal. Hair samples were analysed for methamphetamine using liquid
      chromatography-mass spectrometry. FINDINGS: Treatment retention was significantly
      different between groups, with those who received dexamphetamine remaining in
      treatment for an average of 86.3 days compared with 48.6 days for those receiving
      placebo (P = 0.014). There were significant reductions in self-reported
      methamphetamine use between baseline and follow-up within each group (P <
      0.0001), with a trend to a greater reduction among the dexamphetamine group (P =
      0.086). Based on hair analysis, there was a significant decrease in
      methamphetamine concentration for both groups (P < 0.0001). At follow-up, degree
      of methamphetamine dependence was significantly lower in the dexamphetamine group
      (P = 0.042). Dexamphetamine maintenance was not associated with serious adverse
      events. CONCLUSIONS: The results of this preliminary study have demonstrated that
      a maintenance pharmacotherapy programme of daily sustained-release amphetamine
      dispensing under pharmacist supervision is both feasible and safe. The increased
      retention in the dexamphetamine group, together with the general decreases in
      methamphetamine use, degree of dependence and withdrawal symptom severity,
      provide preliminary evidence that this may be an efficacious treatment option for
      methamphetamine dependence.

PMID- 19839967
TI  - Cross-reactive carbohydrate determinants in diagnostics of occupational allergy -
      preliminary results.

PMID- 19839968
TI  - Adulthood asthma after wheezing in infancy: a questionnaire study at 27 years of
      age.
AB  - BACKGROUND: Wheezing in early childhood is a heterogeneous condition, the
      longterm prognosis varying from total recovery to chronic asthma. Though short
      term outcome has been actively studied, there is lack of data on long-term
      outcome until adulthood. The aim of the study was to evaluate the prevalence and
      risk factors of asthma at 26-29 years of age after early-life wheezing. METHODS:
      At the median age of 27.3 years (range 26.3-28.6), a questionnaire was sent to 78
      study subjects hospitalized for wheezing at <24 months of age, and 59 (76%)
      answered. Asthma, allergy and weight status were compared with selected controls
      followed up from birth and with non-selected population controls recruited for
      this adulthood study. RESULTS: Doctor-diagnosed asthma was present in 20% of the
      former bronchiolitis patients, compared with 5% in the two control groups (OR
      2.1, 95% CI 0.3-17.9 vs selected controls; OR 5.2, 95% CI 1.7-15.8 vs nonselected
      controls). The respective figures for current self-reported asthma were 41% and 7
      10% (OR 11.4, 95% CI 2.3-56.1 vs selected controls; OR 12.2, 95% CI 4.4-33.7 vs
      nonselected controls). Current allergic rhinitis and current smoking were
      significantly associated with asthma, but current overweight or obesity was not.
      In multivariate analyses, early-life wheezing was an independent risk factor of
      adulthood asthma. CONCLUSION: An increased asthma risk in early-life wheezers
      continues, even after many symptom-free years at school age, at least until 27
      years of age.

PMID- 19839969
TI  - Elevated urinary leukotriene E excretion in asthma: a comparison of HPLC-mass
      spectrometry and ELISA.

PMID- 19839970
TI  - Yellow fever vaccine and egg allergy: really a problem?

PMID- 19839971
TI  - CRTH2 mediates the activation of human Th2 cells in response to PGD(2) released
      from IgE/anti-IgE treated nasal polyp tissue.
AB  - BACKGROUND: Mast cells release mediators upon stimulation that contribute to the
      pathogenesis of chronic airway disease, including the recruitment and activation
      of Th2 lymphocytes. The objective was to determine the involvement of
      prostaglandin D(2) (PGD(2)) and its receptors in the chemotaxis of Th2 cells,
      using nasal polyp tissue. METHODS: Tissue explants from ten patients with nasal
      polyposis were incubated with RPMI alone or RPMI containing IgE/anti-IgE for 30
      min. Some samples were treated with diclofenac to inhibit the production of
      PGD(2). Supernatants were assayed for PGD(2) content and for their ability to
      promote human Th2 cell chemotaxis in the presence and absence of a CRTH2
      antagonist. Transcript levels of D protanoid receptor type 1 (DP(1)),
      chemoattractant receptor-homologous receptor expressed on Th2 cells (CRTH2) and
      PGD(2) synthase were analysed by real time PCR. RESULTS: Increased release of
      PGD(2) by nasal polyp tissue treated with IgE/anti-IgE was significantly
      inhibited by preincubation of the tissue with diclofenac. Transcript levels of
      PGD(2) synthase, DP(1) and CRTH2 receptors increased after stimulation with
      IgE/anti-IgE. Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused
      significantly increased chemotaxis of Th2 cells. The levels of PGD(2) produced
      and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac
      inhibited the production of Th2 cell chemotactic activity, and the chemotactic
      effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist
      ramatroban. CONCLUSION: These data suggest that in immunologically activated
      nasal polyp tissue, PGD(2) produced by mast cells promotes the migration of Th2
      cells through a CRTH2 dependent mechanism.

PMID- 19839972
TI  - Association of allergic patients' phenotypes with IgE reactivity to recombinant
      pollen marker allergens.
AB  - BACKGROUND: During the last decade allergen molecules from several allergen
      sources have been produced by recombinant DNA technology. The aim of this study
      was to investigate whether IgE reactivity to recombinant pollen allergens with
      broad and narrow cross-reactivity is associated with clinical phenotypes of
      allergic sensitization. METHODS: Serum IgE reactivity to a panel of six
      recombinant birch and grass pollen allergens was measured by ELISA in pollen
      sensitized patients from Central Europe to define groups of patients with
      exclusive IgE reactivity to rBet v 1, with exclusive reactivity to major grass
      pollen allergens (rPhl p 1, rPhl p 2, rPhl p 5) and with IgE reactivity to cross
      reactive pollen allergens (rBet v 2, rPhl p 7). Patients' clinical phenotypes
      were recorded. IgE responses to tree, grass and weed pollen as well as plant food
      extracts were evaluated in vitro by CAP-FEIA and clinical sensitivities were
      confirmed in vivo by skin prick testing. RESULTS: IgE reactivity to the
      recombinant major birch pollen allergen, rBet v 1, was associated with
      sensitization to pollen from birch, taxonomically related trees and to certain
      plant-derived food. Reactivity to the recombinant timothy grass pollen allergens,
      rPhl p 1, rPhl p 2, rPhl p 5, indicated sensitization to pollen from grasses.
      Patients reacting with the highly cross-reactive allergen rPhl p 7 were
      polysensitized to pollen from unrelated trees, grasses and weeds and rBet v 2
      positive patients were polysensitized to pollen and plant-derived food from
      unrelated plants. CONCLUSIONS: IgE reactivity to recombinant marker allergens is
      associated with clinical phenotypes of allergic sensitization and may be useful
      for the selection of treatment strategies.

PMID- 19839973
TI  - Bee venom immunotherapy - how early is it effective?
AB  - BACKGROUND: Although the effectiveness of venom immunotherapy (VIT) in bee venom
      (BV) allergy has been well established over the past 30 years, no previous study
      has demonstrated its efficacy immediately after reaching the maintenance dose
      (MD). We examined the effectiveness of bee VIT within a week after the MD was
      achieved. METHODS: Bee venom allergic patients underwent conventional or rush
      VIT. Within 1 week after reaching the 100 microg MD, patients were challenged
      with a live bee sting. RESULTS: Seventy-nine of 107 patients (73.8%) who reached
      the MD agreed to be challenged. Seventy patients (88.6%) tolerated the sting
      uneventfully. Four patients (5.1%) developed a very mild local transient rash and
      continued to receive the 100 microg MD. In five patients (6.3%), the sting
      resulted in a mild-moderate systemic reaction. In four of these, the MD was
      increased to 200-250 microg. All four patients uneventfully tolerated a repeated
      sting that was performed within 1 week after achieving the increased MD in three
      patients and after 14 months in the fourth patient. CONCLUSIONS: Bee VIT is
      effective in most patients immediately after the conventional MD has been
      reached. In the minority of patients who are not protected with this dose, an
      increased MD will provide appropriate protection immediately after it is
      achieved. Thus, the dosage of the MD seems to be the major factor affecting
      protection from re-stings rather than the accumulated venom dose or the duration
      on the MD.

PMID- 19839974
TI  - Effector and regulatory mechanisms in allergic contact dermatitis.
AB  - Allergic contact dermatitis (ACD), one of the commonest occupational diseases, is
      a T-cell-mediated skin inflammation caused by repeated skin exposure to contact
      allergens, i.e. nonprotein chemicals called haptens. Allergic contact dermatitis,
      also referred to as contact hypersensitivity, is mediated by CD8+ T cells, which
      are primed in lymphoid organs during the sensitization phase and are recruited in
      the skin upon re-exposure to the hapten. Subsets of CD4+ T cells endowed with
      suppressive activity are responsible for both the down-regulation of eczema in
      allergic patients and the prevention of priming to haptens in nonallergic
      individuals. Therefore, ACD should be considered as a breakdown of the skin
      immune tolerance to haptens. Recent advances in the pathophysiology of ACD have
      demonstrated the important role of skin innate immunity in the sensitization
      process and have revisited the dogma that Langerhans cells are mandatory for CD8+
      T-cell priming. They have also introduced mast cells as a pivotal actor in the
      magnitude of the inflammatory reaction. Finally, the most recent studies address
      the nature, the mode and the site of action of the regulatory T cells that
      control the skin inflammation with the aim of developing new strategies of
      tolerance induction in allergic patients.

PMID- 19839975
TI  - Allergic asthma in patients with common variable immunodeficiency.
AB  - BACKGROUND: Many patients with common variable immunodeficiency (CVID) have a
      clinical history suggestive of allergic respiratory disease. However, in such
      individuals, the prevalence of asthma and the role of atopy have not been well
      established. The objective of this study was to evaluate pulmonary function and
      identify asthma in patients with CVID. We also investigated the role of IgE as a
      trigger of asthma in these patients. METHODS: Sixty-two patients diagnosed with
      CVID underwent spirometry, as well as skin prick testing and in vitro
      determination of serum-specific IgE levels for aeroallergens, together with
      bronchial provocation with histamine and allergen. RESULTS: The most common
      alteration identified through spirometry was obstructive lung disease, which was
      observed in 29 (47.5%) of the 62 patients evaluated. Eighteen (29.0%) of the 62
      patients had a clinical history suggestive of allergic asthma. By the end of the
      study, asthma had been diagnosed in nine (14.5%) patients and atopy had been
      identified in six (9.7%). In addition, allergic asthma had been diagnosed in four
      patients (6.5% of the sample as a whole; 22.2% of the 18 patients with a clinical
      history suggestive of the diagnosis). CONCLUSION: In this study, CVID patients
      testing negative for specific IgE antibodies and suspected of having allergic
      asthma presented a positive response to bronchial provocation tests with
      allergens. To our knowledge, this is the first such study. When CVID patients
      with a history suggestive of allergic asthma test negative on traditional tests,
      additional tests designed to identify allergic asthma might be conducted.

PMID- 19839976
TI  - Pseudo-food allergy caused by carry-over of latex proteins from gloves to food:
      need for prevention?

PMID- 19839977
TI  - Effects of omalizumab on markers of inflammation in patients with allergic
      asthma.
AB  - Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E
      (IgE) plays a key role by activating a variety of inflammatory cells through
      interactions with FcepsilonRI and FcepsilonRII receptors. The role of IgE in
      allergic inflammation provided the rationale for developing omalizumab, a
      humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or
      severe allergic asthma. The reductions in circulating levels of IgE resulting
      from omalizumab treatment leads to reductions in FcepsilonRI expression on mast
      cells, basophils and dendritic cells. This combined effect results in attenuation
      of several markers of inflammation, including peripheral and bronchial tissue
      eosinophilia and levels of granulocyte macrophage colony stimulating factor,
      interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its
      receptors and diminishing dendritic cell FcepsilonRI receptor expression,
      omalizumab may also reduce allergen presentation to T cells and the production of
      Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore,
      explain the reductions in asthma exacerbations and symptoms seen in clinical
      trials in patients with moderate-to-severe or severe, persistent, inadequately
      controlled allergic asthma.

PMID- 19839978
TI  - Anaphylaxis to argan oil.

PMID- 19839979
TI  - Methylprednisolone-induced anaphylaxis: diagnosis by skin test and basophil
      activation test.

PMID- 19839980
TI  - Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and
      the interaction with cat exposure.
AB  - BACKGROUND: Filaggrin gene (FLG) mutations contribute to the development of
      eczema and asthma, but their contribution to sensitization and hay fever remains
      unclear. METHODS: FLG mutations R501X, 2282del4 and R2447X were genotyped in the
      Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to
      evaluate longitudinally, for up to 8 years, their association with eczema,
      sensitization, asthma, hay fever and their interaction with cat exposure.
      RESULTS: The combined FLG mutations were significantly associated with eczema at
      all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4-2.8).
      Combined FLG mutations were associated with both atopic and nonatopic eczema, as
      well as asthma (OR = 3.7; 95% CI: 1.8-7.5). When the FLG 2282del4 mutation was
      analysed separately, it was significantly associated with the development of
      eczema during the first year, having eczema up to 8 years and sensitization at
      the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2;
      95% CI: 2.6-25.9, 6.0; 95% CI: 3.2-11.3 and 5.4; 95% CI: 1.2-23.6 respectively).
      FLG 2282del4 was significantly associated with hay fever from the age 5 years
      onwards (OR = 3.9; 95% CI: 1.5-10.5). CONCLUSIONS: FLG mutations are associated
      both with atopic and nonatopic eczema starting in the first year of life. FLG
      mutations combined with eczema in the first year of life are associated with a
      later development of asthma and hay fever, a clear example of the atopic march.
      We confirm that cat exposure enhances the effect of a FLG mutation on the
      development of eczema and sensitization.

PMID- 19839981
TI  - Response to Gerard Chaouat: Primum Non Nocera.

PMID- 19839982
TI  - Donor screening for human T-cell lymphotrophic virus 1/2: changing paradigms for
      changing testing capacity.
AB  - Organ Procurement and Transplant Network (OPTN) policy currently requires the
      testing of all potential organ donors for human T-cell lymphotrophic virus (HTLV)
      1/2. Most Organ Procurement Organizations (OPO) use the Abbott HTLV-I/HTLV-II
      Enzyme Immunoassay (EIA). This assay will no longer be manufactured after
      December 31, 2009; the only commercially available FDA-licensed assay will be the
      Abbott PRISM HTLV-I/II assay which poses many challenges to OPO use for organ
      donor screening. As a result, screening donors for HTLV-1/2 in a timely manner
      pretransplant after December 31, 2009 will be challenging. The true incidence of
      HTLV-1 in United States (U.S.) organ donors is not well described but appears to
      be low ( approximately 0.03-0.5%). HTLV-1 is associated with malignancy and
      neurological disease; HTLV-2 has not been convincingly associated with disease in
      humans. Donors that are HTLV-1/2 seropositive are infrequently used despite most
      results being either false positive or resulting from HTLV-2 infection. There is
      urgent need to encourage the development of assays, instruments and platforms
      optimized for organ donors that can be used to screen for transmissible disease
      in donors; these must have appropriate sensitivity and specificity to identify
      all infections while minimizing organ loss through false positive testing.

PMID- 19839983
TI  - Naloxone-responsive acute dystonia and parkinsonism following general
      anaesthesia.
AB  - Various movement disorders such as dystonia may acutely develop during or at
      emergence from general anaesthesia in patients with or without pre-existing
      Parkinson disease. These movements are triggered by a variety of drugs including
      propofol, sevoflurane, anti-emetics, antipsychotics and opioids. The postulated
      mechanism involves an imbalance between dopaminergic and cholinergic
      neurotransmitters in the basal ganglia. We report an acute, severe and
      generalised dystonic reaction in an otherwise healthy woman at emergence from
      general anaesthesia, dramatically reversed by the administration of naloxone,
      pointing to a potential role of the fentanyl and morphine that the patient had
      received. Recent literature on the mechanisms of abnormal movements induced by
      opioids are discussed. The severity of the reaction with usual doses of opioids,
      in a patient with no prior history of parkinsonism, led to further investigation
      that demonstrated the possibility of an enhanced susceptibility to opioids,
      involving a genetically determined abnormal function of glycoproteine-P and
      catechol-O-methyltransferase.

PMID- 19839984
TI  - Histochemical analysis of glycoconjugates in the skin of a catfish (arius
      tenuispinis, day).
AB  - A histochemical study using conventional carbohydrate histochemistry (periodic
      acid staining including diastase controls, alcian blue staining at pH 1 and 2.5)
      as well as using a battery of 14 fluorescein isothiocyanate (FITC)-labelled
      lectins to identify glycoconjugates present in 10 different areas of the skin of
      a catfish (Arius tenuispinis) was carried out. The lectins used were: mannose
      binding lectins (Con A, LCA and PSA), galactose-binding lectins (PNA, RCA), N
      acetylgalactosamine-binding lectins (DBA, SBA, SJA and GSL I), N
      acetylglucosamine-binding lectins (WGA and WGAs), fucose-binding lectins (UEA)
      and lectins which bind to complex carbohydrate configurations (PHA E, PHA L).
      Conventional glycoconjugate staining (PAS staining, alcian blue at pH 1 and 2.5)
      showed that the mucous goblet cells contain a considerable amount of
      glycoconjugates in all locations of the skin, whereas the other unicellular gland
      type, the club cells, lacked these glycoconjugates. The glycoproteins found in
      goblet cells are neutral and therefore stain magenta when subjected to PAS
      staining. Alcian blue staining indicating acid glycoproteins was distinctly
      positive at pH 1, but gave only a comparable staining at pH 2.5. The mucus of the
      goblet cells therefore also contains acid glycoproteins rich in sulphate groups.
      Using FITC-labelled lectins, the carbohydrate composition of the glycoproteins of
      goblet cells could be more fully characterized. A distinct staining of the mucus
      of goblet cells was found with the mannose-binding lectins LCA and PSA; the
      galactosamine-binding lectins DBA, SBA and GLS I; the glucosamine-binding lectin
      WGA; and PHA E which stains glycoproteins with complex carbohydrate
      configurations. No reaction occurred with the fucose-binding lectin UEA and the
      sialic acid-specific lectin SNA. In addition, the galactose-binding lectins PNA
      and RCA showed only a weak or completely negative staining of the mucus in the
      goblet cells. The specificity of the lectin staining could be proved by
      inhibiting binding of the lectins by competitive inhibition with the
      corresponding sugars. From these data, we can conclude that the mucus produced by
      the epidermal goblet cells of A. tenuispinis is rich in mannose, N
      acetylgalactosamine and N-acetylglucosamine residues.

PMID- 19839985
TI  - Association analysis of a CCR5 variant with ewe lifetime production in three
      breeds of sheep.

PMID- 19839986
TI  - Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with
      Marfan syndrome.
AB  - The aim of this study was to establish a national database of mutations in the
      fibrillin-1 (FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese
      population. In this study, we screened 294 patients from 157 families for the
      presence of FBN1 mutations using polymerase chain reaction/ denaturing high
      performance liquid chromatography (PCR/DHPLC). We identified 56 mutations in 62
      of the 157 (40%) families including 49 single-base substitutions (36 missense
      mutations, seven nonsense mutations, and six splicing sites), one small
      insertion, four small deletions, one small indel (insertion and deletion), and
      one exonic deletion (Exon 36). When family history was taken into consideration,
      the mutation detection rate rose to 91% (29 of 32). We further investigated the
      phenotypic data and found that one third (47 of 157) of the families fit the
      Ghent criteria for MFS. Based on that data, the mutation rate was 98% (46/47).
      That finding implies that family history and the Ghent criteria play a more
      important role than clinical manifestations in establishing a clinical diagnosis
      of Marfan syndrome. Among the 56 mutations found in this study, 40 (71%) have not
      been registered in the Human Gene Mutation Database (HGMD) or in the Universal
      Mutation Database (UMD). This is the first study of the mutation spectrum of MFS
      in a cohort of patients in Taiwan. The database is expected to considerably
      improve genetic counseling for and medical care of MFS families.

PMID- 19839987
TI  - Optimal robust two-stage designs for genome-wide association studies.
AB  - Optimal robust two-stage designs for genome-wide association studies are proposed
      using the maximum of the recessive, additive and dominant linear trend test
      statistics. These designs combine cost-saving two-stage genotyping with
      robustness against misspecification of the genetic model and are much more
      efficient than designs based on a single model specific test statistic in
      detecting multiple loci with different modes of inheritance. For given power of
      90%, typical cost savings of 34% can be realised by increasing the total sample
      size by about 13% but genotyping only about half of the sample for the full
      marker set in the first stage and carrying forward about 0.06% of the markers to
      the second stage analysis. We also present robust two-stage designs providing
      optimal allocation of a limited budget for pre-existing samples. If a sample is
      available which would yield a power of 90% when fully genotyped, genotyping only
      half of the sample due to a limited budget will typically cause a loss of power
      of more than 55%. Using an optimal two-stage approach in the same sample under
      the same budget restrictions will limit the loss of power to less than 10%. In
      general, the optimal proportion of markers to be followed up in the second stage
      strongly depends on the cost ratio for chips and individual genotyping, while the
      design parameters of the optimal designs (total sample size, first stage
      proportion, first and second stage significance limit) do not much depend on the
      genetic model assumptions.

PMID- 19839989
TI  - Japan's first robot-assisted totally endoscopic mitral valve repair with a novel
      atrial retractor.
AB  - This case report presents the first robot-assisted totally endoscopic mitral
      valve plasty in Japan. A 54-year-old woman was found by echocardiography to have
      grade III mitral valve regurgitation because of prolapse of the posterior
      leaflet. Surgical repair was performed using the da Vinci Surgical System. For
      the totally endoscopic mitral valve repair, a right-sided approach was used
      through four ports. A transthoracic aortic cross-clamp and novel flexible port
      access retractor were inserted through a 5-mm skin incision. Quadrangular
      resection of the posterior leaflet was performed, and an annuloplasty band was
      placed into the atrium. Resection of the valve segment took 13 min, and band
      implementation, 45 min. The total pump time was 197 min and the aortic cross
      clamp time, 117 min. Postoperative echocardiography confirmed the absence of
      mitral insufficiency.

PMID- 19839990
TI  - Forward osmosis process for dialysis fluid regeneration.
AB  - In a preliminary experiment, 38% of the spent dialysis fluid water was reclaimed
      by a forward osmosis process through a cellulose triacetate membrane. The
      simplicity of forward osmosis and its minimal external energy requirements may
      allow the construction of a small bulk device that can reclaim a considerable
      portion of the water used in the patient's dialysis process. For developing an
      acceptable ambulatory dialysis system, decreasing the bulk of the fluid and
      equipment carried on the patient is essential. Forward osmosis may feasibly be
      used for dialysis fluid regeneration in ambulatory dialysis systems.

PMID- 19839991
TI  - Development of a new tissue-engineered sheet for reconstruction of the stomach.
AB  - We have developed tissue-engineered digestive tracts composed of collagen
      scaffold and an inner silicon sheet and successfully used it to repair defects in
      parts of the esophagus, stomach, and small intestine. However, some improvements
      were demanded for clinical usage because the silicon sheet presented technical
      difficulties for suturing and endoscopic removal. New tissue-engineered sheet
      (New-sheet) was composed of a single-piece and reinforced collagen scaffold with
      biodegradable copolymer. One beagle dog was used to evaluate whether New-sheet
      could withstand suturing in comparison with native digestive tracts using a
      tensile tester. Seven beagle dogs had a 5-cm circular defect created in the
      stomach. New-sheet soaked with autologous peripheral blood or bone marrow
      aspirate was sutured to the gastric wall. Endoscopic, histological, and
      immunohistochemical assessment was performed to evaluate regeneration of the
      stomach up to 16 weeks. Tensile strength testing showed that the mucosal side of
      New-sheet had strength almost equivalent to the mucosa of the esophagus (P =
      0.61). Endoscopically, regeneration of the mucosa started from the circumference
      after 4 weeks, but a small linear ulcer was still evident at 16 weeks. The
      regenerated stomach shrank by 60-80% of its original size and histologically
      showed villous mucosa and underlying dense connective tissue.
      Immunohistochemically, the regenerated area expressed alpha-smooth-muscle actin
      but was negative for basic calponin, irrespective of the source of soaked blood.
      New-sheet shows sufficient strength for suturing, no dehiscence, and better
      biocompatibility for clinical use, although further examination will be necessary
      to create a functional digestive tract.

PMID- 19839992
TI  - Comparative assessment of coagulation changes induced by two different types of
      heart-lung machine.
AB  - The cardiopulmonary bypass (CPB) used in heart surgery has a deleterious effect
      on hemostasis. The aim of our study was to assess by means of standard laboratory
      and point-of-care methods changes induced by CPB in coagulation parameters,
      particularly in platelet function, and to determine whether these changes differ
      depending on the type of heart-lung machine (HLM) used: minimal extracorporeal
      circulation system (MECC) and standard HLM. The study enrolled 88 patients
      scheduled for coronary artery bypass surgery performed on pump. Forty-four
      interventions were performed with MECC and 44 with standard HLM. Blood was
      sampled preoperatively, after 30 min on CPB, after weaning from CPB, and 24 h
      postoperatively. Coagulation and platelet function were assessed using multiple
      electrode aggregometry (MEA), rotation thromboelastometry, as well as standard
      laboratory tests. Rotation thromboelastometry and standard laboratory reflected
      significantly impaired hemostasis after weaning from CPB but no significant
      differences between the two groups at different time points. Aggregation
      decreased significantly in both groups as early as 30 min after the institution
      of CPB (P < 0.05, Mann-Whitney U-test) and recovered within the first 24 h
      postoperatively, without reaching the preoperative level. Intraoperatively,
      aggregometry values reflected a significantly more severe reduction of platelet
      function in standard HLM group than in the MECC group (P < 0.01, ProcMixed test).
      Our findings suggest that MEA and thromboelastometry reflect impairment of
      coagulation in cardiac surgery performed on different types of HLM and that
      platelet function is less affected by MECC than by standard HLM.

PMID- 19839993
TI  - A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of
      acute mania in bipolar mania and mixed states.
AB  - OBJECTIVE: Asenapine is approved for bipolar disorder and schizophrenia. This was
      a 3-week, randomized, double-blind, placebo-controlled trial of asenapine for
      treating acute bipolar mania. METHODS: After a single-blind placebo run-in
      period, adults (n = 488) experiencing manic or mixed episodes were randomized to
      flexible-dose sublingual asenapine (10 mg BID on day 1; 5 or 10 mg BID
      thereafter; n = 194), placebo (n = 104), or oral olanzapine (15 mg BID on day 1;
      5-20 mg QD thereafter; n = 191). Primary efficacy, change in Young Mania Rating
      Scale (YMRS) total score from baseline to day 21, was assessed using analysis of
      covariance with last observation carried forward [(LOCF); primary analysis]. A
      mixed model for repeated measures [(MMRM); prespecified secondary analysis] was
      also used to assess efficacy. Tolerability and safety assessments included
      adverse events, physical examinations, extrapyramidal symptom ratings, and
      laboratory values. RESULTS: Mean daily dosages were asenapine 18.2 mg and
      olanzapine 15.8 mg. Significantly greater least squares (LS) mean +/- SE changes
      in YMRS scores were observed on day 2 with asenapine (-3.0 +/- 0.4) and
      olanzapine (-3.4 +/- 0.4) versus placebo (-1.5 +/- 0.5, both p < 0.01) and were
      maintained until day 21 (-10.8 +/- 0.8 with asenapine, -12.6 +/- 0.8 with
      olanzapine; both p < or = 0.0001 versus placebo, -5.5 +/- 1.1) with LOCF. The
      results of MMRM analyses were consistent with those of LOCF. Asenapine had a
      modest impact on weight and metabolic measures. CONCLUSIONS: These results
      indicate that asenapine is rapidly acting, efficacious, and well tolerated for
      patients with bipolar I disorder experiencing an acute manic episode.

PMID- 19839994
TI  - Risperidone for the treatment of acute mania in children and adolescents with
      bipolar disorder: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: To evaluate the efficacy, safety, and tolerability of risperidone
      monotherapy for the treatment of an acute mixed or manic episode in children and
      adolescents with bipolar I disorder. METHODS: This randomized, placebo
      controlled, double-blind, 3-arm study (N = 169) included children and adolescents
      (ages 10-17 years) with a DSM-IV diagnosis of bipolar I disorder, experiencing a
      manic or mixed episode. Study participants were randomized to placebo (n = 58),
      risperidone 0.5-2.5 mg/day (n = 50), or risperidone 3-6 mg/day (n = 61) for 3
      weeks. The primary efficacy measure was change in Young Mania Rating Scale (YMRS)
      total score from baseline to end point. Safety assessments included adverse event
      (AE) monitoring and scores on extrapyramidal symptom rating scales. RESULTS:
      Improvement in mean YMRS total score was significantly greater in risperidone
      treated subjects than in placebo-treated subjects [mean change (SD) -9.1 (11.0)
      for placebo; -18.5 (9.7) for risperidone 0.5-2.5 mg (p < 0.001); -16.5 (10.3) for
      risperidone 3-6 mg (p < 0.001)]. The most common risperidone-associated AEs were
      somnolence, headache, and fatigue. Mean (SD) weight gain was 0.7 (1.9) kg, 1.9
      (1.7) kg, and 1.4 (2.4) kg in the placebo, risperidone 0.5-2.5 mg, and
      risperidone 3-6 mg groups, respectively, during this 3-week study. CONCLUSIONS:
      At daily doses of 0.5-2.5 mg and 3-6 mg, risperidone was effective and well
      tolerated in children and adolescents experiencing acute manic or mixed episodes
      of bipolar I disorder. Results indicate that risperidone 0.5-2.5 mg has a better
      benefit-risk profile than risperidone 3-6 mg.

PMID- 19839996
TI  - Vesicular glutamate transporter mRNA expression in the medial temporal lobe in
      major depressive disorder, bipolar disorder, and schizophrenia.
AB  - BACKGROUND: Altered glutamate transmission has been found in the medial temporal
      lobe in severe psychiatric illnesses, including major depressive disorder (MDD)
      and bipolar disorder (BD). The vesicular glutamate transporters (VGLUTs) have a
      pivotal role in presynaptic release of glutamate into the synaptic cleft. We
      investigated this presynaptic marker in major psychiatric illness by measuring
      transcript expression of the VGLUTs in the medial temporal lobe. METHODS: The
      study sample comprised four groups of 13 subjects with MDD, BD, or schizophrenia
      (SCZ), and a comparison group from the Stanley Foundation Neuropathology
      Consortium. In situ hybridization was performed to quantify messenger RNA (mRNA)
      expression of VGLUT 1, 2, and 3 in medial temporal lobe structures. We also
      examined the same areas of rats treated with antidepressants, a mood stabilizer,
      and antipsychotics to assess the effects of these medications on VGLUT mRNA
      expression. RESULTS: We found decreased VGLUT1 mRNA expression in both MDD and BD
      in the entorhinal cortex (ERC), decreased VGLUT2 mRNA expression in MDD in the
      middle temporal gyrus, and increased VGLUT2 mRNA expression in SCZ in the
      inferior temporal gyrus (ITG). We also found a negative correlation between age
      and VGLUT1 mRNA expression in BD in the ERC and ITG. We did not find any changes
      in VGLUT mRNA expression in the hippocampus in any diagnostic group. We found
      decreased VGLUT1 mRNA expression in rats treated with haloperidol in the temporal
      cortex. CONCLUSIONS: These data indicate region-specific alterations of
      presynaptic glutamate innervation in the medial temporal lobe in the mood
      disorders.

PMID- 19839995
TI  - Association study of 21 circadian genes with bipolar I disorder, schizoaffective
      disorder, and schizophrenia.
AB  - OBJECTIVE: Published studies suggest associations between circadian gene
      polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder
      (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies
      of circadian abnormalities. As replications have not been attempted uniformly, we
      evaluated representative, common polymorphisms in all three disorders. METHODS:
      We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at
      21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477
      screened adult controls. Detected associations were evaluated in relation to two
      published genome-wide association studies (GWAS). RESULTS: Using gene-based
      tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and
      between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets
      of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None
      of the associations remained significant following corrections for multiple
      comparisons. Approximately 15% of the analyzed SNPs overlapped with an
      independent study that conducted GWAS for BPI; suggestive overlap between the
      GWAS analyses and ours was noted at ARNTL. CONCLUSIONS: Several suggestive, novel
      associations were detected with circadian genes and BPI and SZ/SZA, but the
      present analyses do not support associations with common polymorphisms that
      confer risk with odds ratios greater than 1.5. Additional analyses using
      adequately powered samples are warranted to further evaluate these results.

PMID- 19839997
TI  - Similar immune profile in bipolar disorder and schizophrenia: selective increase
      in soluble tumor necrosis factor receptor I and von Willebrand factor.
AB  - BACKGROUND: Alterations in the inflammatory system have been associated with
      schizophrenia and major depression, while bipolar disorder has been less studied.
      Most previous studies examined small samples, and the literature is inconsistent
      with regard to specific underlying immune mechanisms. In the present study, we
      examined markers representing different inflammatory pathways, and the aim was to
      investigate whether the levels of inflammatory parameters in a representative
      sample of bipolar disorder and schizophrenia are elevated compared to healthy
      controls, and to investigate whether the inflammatory profile is different
      between the groups. METHODS: Plasma levels of soluble tumor necrosis factor
      receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6
      (IL-6), high-sensitivity CRP (hs-CRP), soluble CD40L ligand (sCD40L), and von
      Willebrand factor (vWf) were measured with ELISA techniques in a catchment area
      based sample of consecutively referred patients with severe mental disorders [N =
      311, comprising bipolar disorder (n = 125) and schizophrenia (n = 186)] and in
      healthy volunteers (n = 244). RESULTS: Plasma levels of sTNF-R1 and vWf were
      statistically significantly increased in both bipolar disorder and schizophrenia
      compared to controls (p < 0.00001), and were also increased in unmedicated
      patients, but there were no major differences between the two diagnostic groups.
      Controlling for age, gender, ethnicity, cardiovascular disorders, kidney and
      liver function, and other confounders did not affect the results. There were no
      differences in other inflammation factors between the groups. CONCLUSION: The
      present results indicate specific alterations of endothelium-related inflammation
      processes in both bipolar disorder and schizophrenia.

PMID- 19839999
TI  - Performance of the mood disorders questionnaire in a psychiatric outpatient
      setting.
AB  - OBJECTIVES: The Mood Disorders Questionnaire (MDQ) has been the most widely
      studied screening questionnaire for bipolar disorder, though few studies have
      examined its performance in a heterogeneous sample of psychiatric outpatients. In
      the present report from the Rhode Island Methods to Improve Diagnostic Assessment
      and Services (MIDAS) project, we examined the operating characteristics of the
      MDQ in a large sample of psychiatric outpatients presenting for treatment.
      METHODS: A total of 534 psychiatric outpatients were interviewed with the
      Structured Clinical Interview for DSM-IV and asked to complete the MDQ. Missing
      data on the MDQ reduced the number of patients to 480, 10.4% (n = 52) of whom
      were diagnosed with bipolar disorder. RESULTS: Based on the scoring guidelines
      recommended by the developers of the MDQ, the sensitivity of the scale was only
      63.5% for the entire group of bipolar patients. The specificity of the scale was
      84.8%, and the positive and negative predictive values were 33.7% and 95.0%,
      respectively. When impairment was not required to define a case on the MDQ, then
      sensitivity increased to 75.0%, specificity dropped to 78.5%, positive predictive
      value was 29.8%, and negative predictive value was 96.3%. CONCLUSIONS: In a large
      sample of psychiatric outpatients, we found that the MDQ, when scored according
      to the developers' recommendations, had inadequate sensitivity as a screening
      measure. After the threshold to determine MDQ caseness was lowered by not
      requiring moderate or severe impairment, the sensitivity of the scale increased,
      but specificity decreased, and positive predictive value remained below 30%.
      These results raise questions regarding the MDQ's utility in routine clinical
      practice.

PMID- 19840000
TI  - Cigarette smoking is associated with suicidality in bipolar disorder.
AB  - OBJECTIVES: Cigarette smoking in individuals with bipolar disorder has been
      associated with suicidal behavior, although the precise relationship between the
      two remains unclear. METHODS: In this prospective observational study of 116
      individuals with bipolar disorder, we examined the association between smoking
      and suicidality as measured by Linehan's Suicide Behaviors Questionnaire (SBQ)
      and prospective suicide attempts over a nine-month period. Impulsivity was
      measured by the Barratt Impulsiveness Scale. RESULTS: Smoking was associated with
      higher baseline SBQ scores in univariate and adjusted analyses, but was not
      significant after statistical adjustment for impulsivity in a regression model. A
      higher proportion of smokers at baseline made a suicide attempt during the follow
      up period (5/31, 16.1%) compared to nonsmokers (3/85, 3.5%); p = 0.031, odds
      ratio = 5.25 (95% confidence interval: 1.2-23.5). Smoking at baseline also
      significantly predicted higher SBQ score at nine months. CONCLUSIONS: In this
      study, current cigarette smoking was a predictor of current and nine-month
      suicidal ideation and behavior in bipolar disorder, and it is likely that
      impulsivity accounts for some of this relationship.

PMID- 19839998
TI  - Sexually dimorphic features of vermis morphology in bipolar disorder.
AB  - OBJECTIVES: The cerebellar vermis is increasingly implicated in bipolar disorder
      (BD). In this study, we investigated vermis morphology in BD using a quantitative
      volumetric analysis. METHODS: Volumes for total vermis and vermis subregions V1
      (lobules I-V), V2 (lobules VI-VII), and V3 (lobules VIII-X) were calculated using
      high-resolution structural magnetic resonance imaging obtained from 44
      individuals with BD (25 females and 19 males) and 43 healthy comparison (HC)
      subjects (26 females and 17 males). Total vermis volumes were compared between
      the BD and HC groups. Potential effects of vermis subregions and clinical
      features were explored. RESULTS: Total vermis volumes were significantly larger
      in the BD group than in the HC group (p = 0.02). There was a significant group-by
      sex interaction (p = 0.02). Total vermis volumes were significantly larger in
      males with BD than HC males (p = 0.004); vermis volumes did not differ
      significantly between females with and without BD (p = 0.95). Subregion analyses
      showed a trend-level interaction between diagnosis and subregion (p = 0.07) in
      which subregion V1 volumes were significantly larger in BD participants (p =
      0.001), with differences primarily driven by males (p = 0.001). CONCLUSIONS: Our
      findings demonstrate increases in cerebellar vermis volumes in males with BD.
      These findings support the presence of structural alterations in the cerebellar
      vermis in BD and furthermore the influence of sex on such changes.

PMID- 19840001
TI  - Patient history must be incorporated into any guidelines.

PMID- 19840002
TI  - Comment to Dr. Yatham regarding tamoxifen listed as a third-line recommendation
      for the pharmacological treatment of acute mania.

PMID- 19840008
TI  - Epidemiology of testicular cancer.
AB  - Testicular cancer is of interest and importance because its incidence has been
      increasing in most countries over the past four decades. Although it remains an
      uncommon malignancy overall accounting for 1-2% of all tumours in men, testicular
      cancer is the most common malignancy in young men. There is marked geographical
      variation in the incidence of testicular cancer, with the highest incidence among
      men in Nordic countries and lowest incidence among men in the Middle East and
      Asia. The association between some risk factors, including cryptorchidism, a
      previous history of testicular cancer and a family history of testicular cancer,
      and the incidence of testicular cancer has been widely reported. We reviewed
      published reports and present the evidence to support or refute the association
      between the well-established and the less well-established risk factors and the
      incidence of testicular cancer.

PMID- 19840010
TI  - Contemporary radiological imaging of testicular cancer.

PMID- 19840009
TI  - Molecular events in germ cell tumours: linking chromosome-12 gain, acquisition of
      pluripotency and response to cisplatin.
AB  - Germ cell tumours (GCTs) represent the leading cause of cancer-related morbidity
      and mortality in young men aged 18-35 years. Transformation of the cell of origin
      results in tumours with several unique properties. GCTs are characterized by gain
      of the short arm of chromosome 12 in almost all cases, a frequency of genomic
      alteration not seen in any other solid tumours. GCTs are truly pluripotent,
      giving rise to cells of somatic and extra-embryonic lineages, which results in
      tumours with a spectrum of differentiation that rivals that seen in normal
      embryogenesis and development. Despite the presence of genomic instability and
      many oncogenic changes, GCTs are highly curable, even in the metastatic setting,
      due to their extreme sensitivity to cisplatin-based chemotherapy. In this review
      we highlight some of the molecular events associated with the genesis,
      differentiation and chemotherapeutic response of these tumours, and discuss how
      these alterations are linked with biological features unique to germ cells.

PMID- 19840011
TI  - Contralateral testicular biopsy in testis cancer: current concepts and
      controversies.
AB  - Of all patients with unilateral testis cancer, approximately 5% harbour
      testicular intraepithelial neoplasia (TIN) in their contralateral testicle that
      will progress into an invasive germ cell tumour over time. The accurate diagnosis
      of TIN by a random two-site surgical testis biopsy and effective therapy by local
      radiation has led to the concept of a contralateral screening biopsy in all
      patients with testis cancer. However, screening and preventive treatment are only
      indicated if the therapeutic outcome of the screened population is improved, and
      the physiological function of the affected organ is not impaired. Based on a
      critical review of previous reports, some drawbacks of this policy have to be
      considered and question the routine indication for contralateral testis biopsy:
      (i) all TIN-negative patients still have to undergo meticulous follow-up for
      metachronous testis cancer due to a false negative biopsy rate of 0.5-1.0%; (ii)
      local radiation of TIN results in irreversible infertility due to eradication of
      spermatogenesis; (iii) local radiation of TIN results in an impairment of
      endocrine Leydig cell function in 25% of the patients; (iv) therapeutic outcome
      and prognosis will not be improved in irradiated patients as compared to patients
      on surveillance; (v) local tumour resection for the management of metachronous
      testicular cancer represents an effective and viable option. Current reports do
      not support the strategy of contralateral testis biopsy in all patients with
      unilateral testicular germ cell tumours. According to the recommendations of the
      European Germ Cell Cancer Consensus Group, a testis biopsy might be offered to
      high-risk patients for contralateral TIN (testicular volume <12 mL, history of
      cryptorchidism, age <30 years).

PMID- 19840012
TI  - Surveillance in stage I nonseminomatous germ cell tumours of the testis.

PMID- 19840013
TI  - Evolving concepts in stage I seminoma.

PMID- 19840014
TI  - Surgical management of low-stage nonseminomatous germ cell testicular cancer.
AB  - The optimal treatment of low-stage nonseminomatous germ cell testicular cancer
      (NSGCT) is controversial. For clinical stage (CS) I NSGCT, retroperitoneal lymph
      node dissection (RPLND), two cycles of chemotherapy and surveillance are all
      accepted treatment options. For CS IIA-B, standard treatments include RPLND (+/-
      adjuvant chemotherapy) and induction chemotherapy (+/- RPLND). The long-term
      survival rate is >97% for CS I and 95% for CS IIA-B NSGCT, regardless of the
      treatment received. The risk of retroperitoneal metastasis varies by clinical
      stage (25-35% for CS I, 65-85% for CS IIA-B), and the presence of lymphovascular
      invasion and percentage of embryonal carcinoma in the primary tumour. Patients
      with elevated serum tumour markers (STMs) and adenopathy of >3 cm are at high
      risk of having occult systemic disease. Compared with chemotherapy, RPLND is
      associated with a considerably more favourable long-term morbidity profile and is
      the most effective method for controlling the retroperitoneum. Surveillance is
      associated with the lowest risk of long-term complications. As such, we favour
      surveillance for low-risk CS I, induction chemotherapy for those at high risk of
      systemic disease (elevated STM, adenopathy >3 cm), and RPLND for all others.
      Modified template dissections reduce the risk of ejaculatory dysfunction, but
      might increase the risk of local recurrence. Therefore, we favour a full
      bilateral template dissection with nerve-sparing in patients with low-stage
      NSGCT. The therapeutic efficacy of laparoscopic RPLND is not proven and currently
      should be considered a staging procedure only. Adjuvant chemotherapy after RPLND
      is typically restricted to patients with pathological stage N2-3 disease.

PMID- 19840015
TI  - Retroperitoneal lymph node dissection: reassessment of modified templates.
AB  - The retroperitoneum is the initial metastatic site in 90% of patients with
      nonseminomatous germ cell tumours (NSGCTs) of the testis. A retroperitoneal lymph
      node dissection (RPLND) provides accurate staging and effective therapy,
      minimizes the need for adjuvant chemotherapy in patients with low-volume
      metastases, and optimizes durable cure rates. We review the rationale for and
      development of RPLND, focusing specifically on the advantages and limitations of
      the variable surgical templates. Bilateral RPLND has a long-standing record of
      maximizing cancer control and minimizing secondary therapy. Both modified
      templates and prospective nerve-sparing techniques were introduced to optimize
      rates of antegrade ejaculation. Limited resections as advocated by modified
      templates are appealing in the setting of primary RPLND but can be associated
      with a 3-23% risk of residual disease. Modified templates have also been
      advocated for highly selected patients after chemotherapy but, if applied to all
      patients undergoing surgery after chemotherapy, will lead to an unacceptably high
      rate of residual disease, even in patients with small masses after chemotherapy.
      For patients undergoing primary or post-chemotherapy RPLND, a full bilateral
      template (with nerve-sparing when appropriate) maximizes cure rates while
      minimizing ejaculatory morbidity and the subsequent need for chemotherapy.

PMID- 19840016
TI  - Laparoscopic retroperitoneal lymph node dissection: current concepts and
      limitations.

PMID- 19840017
TI  - Chemotherapy for clinical stage I nonseminomatous germ cell tumours.

PMID- 19840018
TI  - Management of good risk germ-cell tumours.
AB  - Following the implementation of cisplatin-containing combined chemotherapy,
      patients with good-risk metastatic germ-cell cancer have an excellent prognosis.
      Since the 1980s, bleomycin, etoposide and cisplatin (BEP) have become the
      standard chemotherapy regimen for these patients. In view of both the high
      curative potential of BEP chemotherapy and the treatment-related side-effects,
      trials were carried out in patients with the greatest chance of cure to develop
      regimens with an improved toxicity profile while maintaining efficacy. Following
      the results of these trials, the standard chemotherapy in good-risk disease has
      been reduced from four cycles of BEP (4BEP) to three cycles of BEP (3BEP). Four
      cycles of etoposide and cisplatin (4EP) is an alternative treatment regimen, with
      similar efficacy. Studies that explored additional adjustments in the BEP regimen
      to further decrease toxicity have shown that the lower threshold of efficacy has
      been reached, and that the efficacy of the chemotherapy is compromised.
      Especially during the last decade, important long-term side-effects after the
      treatment of germ-cell cancers have been recognized. Chemotherapy in patients
      with germ-cell cancer increases the risk of developing cardiovascular disease and
      second malignant neoplasms. Whether 3BEP or 4EP is the optimal chemotherapy
      regimen for the future remains to be identified. Possibly differences in acute
      and late toxicities attributed to chemotherapy might eventually identify the best
      strategy.

PMID- 19840019
TI  - Management of poor-prognosis or relapsed germ-cell cancer.

PMID- 19840020
TI  - High-dose chemotherapy in nonseminomatous germ cell cancer.

PMID- 19840021
TI  - Retroperitoneal lymph node dissection after chemotherapy.
AB  - Retroperitoneal lymph node dissection after chemotherapy (PC-RPLND) plays a
      crucial role in managing patients with advanced germ cell tumours (GCTs). In the
      last few years improvements in radiographic staging, a better understanding of
      the role of serum tumour markers, and the introduction of cisplatin-based
      chemotherapy have all contributed to this surgical therapy. PC-RPLND is necessary
      when residual radiographic abnormalities are present after chemotherapy. The need
      for a PC-RPLND in the face of normal findings from computed tomography (CT) is
      controversial. CT criteria alone are not sufficiently reliable to distinguish
      viable tumour or teratoma from necrosis. No combination of variables can predict
      negative retroperitoneal pathology with sufficient accuracy after induction
      chemotherapy. Unresected teratoma or viable GCT are at least partly
      chemorefractory and, if untreated, will progress. So completeness of resection is
      an independent and consistent predictive variable of clinical outcome. In PC
      RPLND surgical margins should not be compromised in an attempt to preserve
      ejaculation, although nerve-sparing dissections are possible in patients with
      marker normalization after chemotherapy and necrotic tissue in frozen-section
      histology. In these patients nerve-sparing techniques and the reduction of
      surgical field to the left- or right-sided template are applicable to preserve
      antegrade ejaculation and consecutive fertility. The size and location of
      residual masses coupled with the retroperitoneal desmoplastic reaction make PC
      RPLND a technically demanding procedure that should be performed by experienced
      surgeons in dedicated referral centres.

PMID- 19840022
TI  - Late relapse of nonseminomatous germ cell tumours.
AB  - Late relapses of nonseminomatous cell tumours (NSGCTs) are rare and occur by
      definition at > or =2 years after successful treatment. They represent a major
      challenge of current treatment and follow-up of the affected patients. We present
      relevant literature on late-relapsing NSGCTs to provide an overview over the
      effect of primary treatment, patient and tumour characteristics. Of all patients
      with NSGCT, 1-6% have a late relapse, with those having extragonadal GCTs being
      at greatest risk. The predominant site of relapse is the retroperitoneal space.
      Suboptimal primary treatment, especially insufficient retroperitoneal surgery,
      increases the risk of late relapses. Radical surgery is probably the most
      important treatment, with advances in salvage chemotherapy adding to the improved
      cure rates. Treatment at an experienced institution ensures a 5-year cancer
      specific survival of >50%, and this approaches 100% in case of single-site mature
      teratoma. Diagnosis and proper treatment of patients with late-relapsing NSGCTs
      is challenging and should be restricted to experienced centres only. Referral of
      late-relapsing patients to high-volume institutions ensures the best chances of
      cure and enables increasing understanding of tumour biology and the clinical
      course of these patients.

PMID- 19840023
TI  - Short- and long-term morbidity after treatment for testicular cancer.
AB  - Patients with testicular cancer are at risk of having severe short-term and life
      threatening long-term effects; we reviewed previous reports of these sequelae.
      After orchidectomy and before further treatment patients have major mental
      distress which gradually decreases during the treatment phase. Gastrointestinal
      side-effects dominate during both chemo- and radiotherapy, with the risk of
      severe haematological, infectious and thromboembolic complications during
      chemotherapy. Long-term sequelae comprise second cancers, cardiovascular
      morbidity/mortality and gonadal dysfunction. Nevertheless, 70% of patients who
      attempt paternity after treatment are successful. About 20% of patients develop
      long-term neuro- and/or ototoxicity. The long-term quality of life of survivors
      of testicular cancer is comparable to that of controls. Risk-adapted treatment of
      patients with testicular cancer and adequate follow-up of those at risk of life
      threatening toxicity are ways to reduce the short- and long-term morbidity in
      survivors. Patients should be informed about these potential complications and
      the importance of adjusting their lifestyle (e.g. smoking habits, physical
      activity and weight control).

PMID- 19840024
TI  - Dopamine and gamma-aminobutyric acid are colocalized in restricted groups of
      neurons in the sea lamprey brain: insights into the early evolution of
      neurotransmitter colocalization in vertebrates.
AB  - Since its discovery, the possible corelease of classic neurotransmitters from
      neurons has received much attention. Colocalization of monoamines and amino
      acidergic neurotransmitters [mainly glutamate and dopamine (DA) or serotonin] in
      mammalian neurons has been reported. However, few studies have dealt with the
      colocalization of DA and gamma-aminobutyric acid (GABA) in neurons. With the aim
      of providing some insight into the colocalization of neurotransmitters during
      early vertebrate phylogeny, we studied GABA expression in dopaminergic neurons in
      the sea lamprey brain by using double-immunofluorescence methods with anti-DA and
      anti-GABA antibodies. Different degrees of colocalization of DA and GABA were
      observed in different dopaminergic brain nuclei. A high degree of colocalization
      (GABA in at least 25% of DA-immunoreactive neurons) was observed in populations
      of the caudal rhombencephalon, ventral isthmus, postoptic commissure nucleus,
      preoptic nucleus and in granule-like cells of the olfactory bulb. A new DA
      immunoreactive striatal population that showed colocalization with GABA in about
      a quarter of its neurons was observed. In the periventricular hypothalamus,
      colocalization was observed in only a few cells, despite the abundance of DA- and
      GABA-immunoreactive neurons, and no double-labelled cells were observed in the
      paratubercular nucleus. The frequent colocalization of DA and GABA reveals that
      the dopaminergic populations of lampreys are more complex than previously
      reported. Double-labelled fibres or terminals were observed in different brain
      regions, suggesting possible corelease of DA and GABA by these lamprey neurons.
      The present results suggest that colocalization of DA and GABA in neurons
      appeared early in vertebrate evolution.

PMID- 19840025
TI  - Quantitative analysis of patch patterns in mosaic tissues with ClonalTools
      software.
AB  - Quantitative analysis of mosaic tissues is a powerful method for following
      developmental lineages; however, analytical techniques are often subjective and
      repetitious. Here a flexible, semi-automated image analysis method for mosaic
      patterns is described. ClonalTools is a free customizable tool-set designed for
      the open-source image analysis package ImageJ. Circular, polygonal or linear one
      dimensional mosaic arrays can be interrogated to provide measurements of the
      total number and width of positive and negative patches in a region of interest.
      These results are adjusted for the effects of random clumping using a previously
      described method to correct for differences in the contribution of the positive
      and negative cell type. The applicability of ClonalTools to different systems is
      discussed with reference to the analysis of mosaic patterns in the mouse corneal
      epithelium and adrenal cortex and in the outgrowth of neurites from explant
      cultures of mouse retina as example systems. To validate ClonalTools
      quantitatively, a recently published manual clonal analysis of the corneal
      epithelium of X-inactivation beta-Gal-mosaic mice was re-analysed. The semi
      automated results did not differ significantly from the published data. Rapid
      quantification of such patterns to produce biologically relevant results
      represents a welcome improvement in terms of ease and speed of use over previous
      methods.

PMID- 19840027
TI  - Selective and specific internalization of clostridial C3 ADP-ribosyltransferases
      into macrophages and monocytes.
AB  - The C3 transferases from Clostridium botulinum (C3bot) and Clostridium limosum
      (C3lim) mono-ADP-ribosylate and thereby inactivate RhoA, -B and -C of eukaryotic
      cells. Due to their extremely poor cellular uptake, C3 transferases were supposed
      to be exoenzymes rather than exotoxins, challenging their role in pathogenesis.
      Here, we report for the first time that low concentrations of both C3lim and
      C3bot are selectively internalized into macrophages/monocytes in less than 3 h,
      inducing the reorganization of the actin cytoskeleton by ADP-ribosylation of Rho.
      We demonstrate that C3 transferases are internalized into the cytosol of
      macrophages/monocytes via acidified early endosomes. Bafilomycin A1, an inhibitor
      of endosomal acidification, protected J774A.1 macrophages and human promyelotic
      leukaemia cells (HL-60) from intoxication by C3. Moreover, confocal laser
      scanning microscopy revealed colocalization of C3 with early endosomes. An
      extracellular acidic pulse enabled direct translocation of cell surface-bound C3
      across the cytoplasmic membrane to the cytosol. In line with this finding, both
      C3 proteins exhibited membrane activity in lipid bilayer membranes only under
      acidic conditions (pH < 5.5). In conclusion, we identified macrophages/monocytes
      as target cells for clostridial C3 transferases and shed light on their selective
      uptake mechanism, which might contribute to understand the role of C3
      transferases in pathogenesis.

PMID- 19840028
TI  - Rac1 inactivation by lethal toxin from Clostridium sordellii modifies focal
      adhesions upstream of actin depolymerization.
AB  - Inactivation of different small GTPases upon their glucosylation by lethal toxin
      from Clostridium sordellii strain IP82 (LT-82) is already known to lead to cell
      rounding, adherens junction (AJ) disorganization and actin depolymerization. In
      the present work, we observed that LT-82 induces a rapid dephosphorylation of
      paxillin, a protein regulating focal adhesion (FA), independently of inactivation
      of paxillin kinases such as Src, Fak and Pyk2. Among the small GTPases
      inactivated by this toxin, including Rac, Ras, Rap and Ral, we identified Rac1,
      as responsible for paxillin dephosphorylation using cells overexpressing
      Rac1(V12). Rac1 inactivation by LT-82 modifies interactions between proteins from
      AJ and FA complexes as shown by pull-down assays. We showed that in Triton X-100
      insoluble membrane proteins from these complexes, namely E-cadherin, beta
      catenin, p120-catenin and talin, are decreased upon LT-82 intoxication, a
      treatment that also induces a rapid decrease in cell phosphoinositide content.
      Therefore, we proposed that Rac inactivation by LT-82 alters phosphoinositide
      metabolism leading to FA and AJ complex disorganization and actin
      depolymerization.

PMID- 19840029
TI  - Effect of syndecan-1 overexpression on mesenchymal tumour cell proliferation with
      focus on different functional domains.
AB  - OBJECTIVES: Syndecan-1 is a transmembrane proteoglycan involved in various
      biological processes. Its extracellular, transmembrane and cytoplasmic domains
      may all participate in signal transduction. The aim of this study was to
      investigate the biological roles of these domains of syndecan-1. MATERIALS AND
      METHODS: We transfected cells of two mesenchymal tumour cell lines with a full
      length syndecan-1 construct and three truncated variants, namely 78 construct
      lacking the EC domain with exception of DRKE sequence; 77 construct lacking
      extracellular the whole domain and RMKKK corresponding to a short cytoplasmic
      motif. Subcellular distribution was revealed using confocal laser microscopy.
      Overexpression of the constructs was verified using real-time RT-PCR and by FACS
      analysis and effects of syndecan-1 on cell behaviour were explored. Cell cycle
      analysis allowed for dissection of mechanisms regulating cell proliferation.
      RESULTS: Overexpression of syndecan-1 influenced expression profile of the other
      syndecan members, and decreased tumour cell proliferation significantly by two
      mechanisms, as follows: increased length of G0/G1 phase was the most evident
      change in RMKKK and 77 transfectants, whereas prolonged S phase was more obvious
      in full-length transfectants. Overexpression of syndecan-1 changed the tumour
      cell morphology in an epithelioid direction. CONCLUSIONS: Both full-length and
      truncated syndecan-1 inhibited proliferation of the mesenchymal tumour cells,
      providing new insights into the importance for cancer growth of different
      functional domains of this proteoglycan.

PMID- 19840030
TI  - Comparison of Rickettsia conorii growth within different cell lines by real-time
      quantitative PCR.

PMID- 19840031
TI  - New molecular method for the detection of human papillomavirus type 16
      integration.
AB  - Human papillomavirus (HPV) infection is the cause of cervical cancer. Integration
      of HPV-16 DNA in cervical cells is considered to be a key event in the
      progression towards invasive cancer, but little is known about this event in anal
      carcinogenesis. The integration could be a useful biomarker for cancer
      progression. Optimized assays are needed to determine the value of real-time
      detection of HPV integration in longitudinal studies, and this approach is only
      possible with a high-throughput assay. The aim of this study was to develop a new
      multiplex real-time PCR assay based on simultaneous amplification of the E2 and
      E6 HPV open reading frames (ORFs) in order to assess the physical status
      (episomal and/or integrated) of HPV-16 in anal cells of HIV-positive men. The
      comparative threshold (Ct) cycle values for E2 and E6 obtained for SiHA cells and
      artificial mixtures of episomal and integrated DNA were as expected: similar Ct
      for episomal forms and absence of E2 amplification for integrated forms. The
      multiplex real-time PCR was tested in 77 consecutive samples from individual HIV
      infected patients with HPV-16 anal infection. The integration of HPV-16 was
      detected in 25 (32%) patients: 23 as mixed (episomal and integrated) and two as
      completed integrated forms. The integration occurs in the early stage of anal
      lesions and was associated with the severity of the lesions (p 0.004). The
      multiplex real-time PCR assay developed in the course of this study was shown to
      be a simple, sensitive, specific and inexpensive technique which may be applied
      routinely to detect HPV-16 integration.

PMID- 19840032
TI  - Comparison of three real-time PCR methods with blood smears and rapid diagnostic
      test in Plasmodium sp. infection.
AB  - In cases of malaria, rapid and accurate diagnosis of Plasmodium sp. is essential.
      In this study three different quantitative, real-time PCR methods were compared
      with routine methods used for malaria diagnosis. A comparative study was
      conducted prospectively in the laboratories of Montpellier and Nimes University
      Hospitals. The methods used for routine diagnostic malaria testing consisted of
      microscopic examination of Giemsa-stained blood smears and rapid diagnostic
      tests. Three quantitative real-time PCR methods (qRT-PCR) were tested: qRT-PCR1
      amplified a specific sequence on the P. falciparum Cox1 gene, qRT-PCR2 amplified
      a species-specific region of the multicopy 18S rDNA, and qRT-PCR3 amplified a
      mitochondrial DNA sequence. Among the 196 blood samples collected, 73 samples
      were positive in at least one of the five tests. Compared with the routine
      method, there were no false negatives for P. falciparum diagnosis in either qRT
      PCR1 or qRT-PCR3. In all P. ovale, P. vivax and P. malariae infections diagnosed
      from blood smears, qRT-PCR1 was negative, as expected, whereas qRT-PCR2 and qRT
      PCR3 were positive and concordant (simple kappa coefficient = 1). One negative
      sample from microscopy was positive with both qRT-PCR2 and qRT-PCR3. Together,
      qRT-PCR3 and the combined qRT-PCR1 and qRT-PCR2 were concordant with routine
      methods for malaria diagnosis (99% and 99.5%, respectively). These three rapid,
      molecular qRT-PCR methods, used alone or in association, showed excellent
      results, with high concordance, accuracy and reliability in malaria diagnosis.

PMID- 19840033
TI  - Preliminary evaluation of novel 68Ga-DOTAVAP-PEG-P2 peptide targeting vascular
      adhesion protein-1.
AB  - SUMMARY INTRODUCTION: Expression of vascular adhesion protein-1 (VAP-1) is
      induced at the sites of inflammation where extravasation of leukocytes from blood
      to the peripheral tissue occurs. VAP-1 is a potential target for anti
      inflammatory therapy and for in vivo imaging of inflammation. Purpose of this
      study was to preliminarily evaluate a novel VAP-1-targeting peptide as a
      potential PET imaging agent. METHODS: Cyclic 17-amino-acid peptide selected from
      phage display libraries was 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''
      tetraacetic acid (DOTA) conjugated via 8-amino-3,6-diooxaoctanoyl linker
      (polyethylene glycol, PEG derivative) and labelled with (68)Ga ((68)Ga-DOTAVAP
      PEG-P2). In vitro stability of (68)Ga-DOTAVAP-PEG-P2 was determined in saline,
      rat plasma and human plasma by radio-HLPC. Lipophilicity was measured by
      calculating octanol-water partition coefficient (logP). Whole-body distribution
      kinetics and stability after intravenous injection in healthy rats was studied in
      vivo by PET imaging, ex vivo by measuring radioactivity of excised tissues, and
      by radio-HPLC. RESULTS: In vitro the (68)Ga-DOTAVAP-PEG-P2 remained stable >4 h
      in saline and rat plasma, but degraded slowly in human plasma after 2 h of
      incubation. The logP value of (68)Ga-DOTAVAP-PEG-P2 was -1.3. In rats, (68)Ga
      radioactivity cleared rapidly from blood circulation and excreted quickly in
      urine. At 120 min after injection the fraction of intact (68)Ga-DOTAVAP-PEG-P2
      were 77 +/- 6.0% and 99 +/- 1.0% in rat plasma and urine, respectively.
      CONCLUSIONS: These basic and essential in vitro and in vivo studies of the new
      VAP-1 targeting peptide revealed promising properties for an imaging agent.
      Further investigations to clarify in vivo VAP-1 targeting are warranted.

PMID- 19840034
TI  - Biological marker candidates of Alzheimer's disease in blood, plasma, and serum.
AB  - At the earliest clinical stages of Alzheimer's disease (AD), when first symptoms
      are mild, making a reliable and accurate diagnosis is difficult. AD related brain
      pathology and underlying molecular mechanisms precede symptoms. Biological
      markers can serve as supportive early screening and diagnostic tools as well as
      indicators of presymptomatic biochemical change. Moreover, biomarkers cover a
      variety of roles and functions such as disease prediction, indicating disease
      acuity and progression, and may ensure biological mapping of treatment outcome.
      Early screening, detection, and diagnosis of AD would permit earlier disease
      modifying intervention at potentially reversible stages. To date, most
      established biological markers from both cerebrospinal fluid neurochemistry and
      structural and functional neuroimaging have not reached widespread clinical
      application. Crucial remaining problems, such as easy acceptance and application
      of a test, cost-effectiveness, and noninvasiveness, need to be resolved. The
      development and validation of precise, reliable, and robust tests and biomarkers
      in blood, plasma, or serum has therefore been for a long time the ultimate focus
      of many research groups worldwide. Blood-based testing will most likely be the
      prerequisite to future sensitive screening of large populations at risk of AD and
      the baseline in a diagnostic flow approach to AD. The status and emerging
      perspectives on hypothesis and exploratory-based candidate biomarkers derived
      from blood, plasma, and serum are reviewed and discussed.

PMID- 19840035
TI  - Differential development of selectivity for faces and bodies in the fusiform
      gyrus.
AB  - Viewing faces or bodies activates category-selective areas of visual cortex,
      including the fusiform face area (FFA), fusiform body area (FBA), and
      extrastriate body area (EBA). Here, using fMRI, we investigate the development of
      these areas, focusing on the right FFA and FBA. Despite the overlap of
      functionally defined FFA and FBA (54%-75% overlap), we found that these regions
      developed along different trajectories. With age (7-32 years old), the FFA
      gradually increased in size and selectivity, and was significantly larger and
      more face-selective in adults than children. By contrast, the size and
      selectivity of the FBA did not correlate with age, and were equivalent in
      children and adults. Whereas in adults the FFA and FBA were comparable in size,
      in children the FBA was on average 70% larger than the FFA. These findings
      suggest that, in children, the fusiform gyrus is predominantly selective for
      bodies, with commensurate face-selective responses apparent later in development.
      Moreover, differences in the development of the FFA and FBA indicate that
      overlapping functional brain areas, supported by the same anatomical structure,
      can develop along different trajectories.

PMID- 19840036
TI  - Auditory verb perception recruits motor systems in the developing brain: an fMRI
      investigation.
AB  - This study investigated neural activation patterns during verb processing in
      children, using fMRI (functional Magnetic Resonance Imaging). Preschool children
      (aged 4-6) passively listened to lists of verbs and adjectives while neural
      activation was measured. Findings indicated that verbs were processed differently
      than adjectives, as the verbs recruited motor systems in the frontal cortex
      during auditory perception, but the adjectives did not. Further evidence
      suggested that different types of verbs activated different regions in the motor
      cortex. The results demonstrate that the motor system is recruited during verb
      perception in the developing brain, reflecting the embodied nature of language
      learning and processing.

PMID- 19840037
TI  - Executive functions in adolescence: inferences from brain and behavior.
AB  - Despite the advances in understanding cognitive improvements in executive
      function in adolescence, much less is known about the influence of affective and
      social modulators on executive function and the biological underpinnings of these
      functions and sensitivities. Here, recent behavioral and neuroscientific studies
      are summarized that have used different approaches (cognition, emotion,
      individual differences and training) in the study of adolescent executive
      functions. The combination of these different approaches gives new insight into
      this complex transitional phase in life, and marks adolescence as not only a
      period of vulnerabilities, but also great opportunities in terms of training
      possibilities and interventions.

PMID- 19840038
TI  - Domestic dogs comprehend human communication with iconic signs.
AB  - A key skill in early human development is the ability to comprehend communicative
      intentions as expressed in both nonlinguistic gestures and language. In the
      current studies, we confronted domestic dogs (some of whom knew many human
      'words') with a task in which they had to infer the intended referent of a
      human's communicative act via iconic signs--specifically, replicas and
      photographs. Both trained and untrained dogs successfully used iconic replicas to
      fetch the desired item, with many doing so from the first trial. Dogs' ability to
      use photographs in this same situation was less consistent. Because simple
      matching to sample in experimental contexts typically takes hundreds of trials
      (and because similarity between iconic sign and target item did not predict
      success), we propose that dogs' skillful performance in the current task reflects
      important aspects of the comprehension of human communicative intentions.

PMID- 19840039
TI  - Addendum to Kaminski et al. (2009).

PMID- 19840040
TI  - Lifespan differences in cortical dynamics of auditory perception.
AB  - Using electroencephalographic recordings (EEG), we assessed differences in
      oscillatory cortical activity during auditory-oddball performance between
      children aged 9-13 years, younger adults, and older adults. From childhood to old
      age, phase synchronization increased within and between electrodes, whereas whole
      power and evoked power decreased. We conclude that the cortical dynamics of
      perceptual processing undergo substantial reorganization from childhood to old
      age, and discuss possible reasons for the inverse relation between age trends in
      phase synchronization and power, such as lifespan differences in neural
      background activity, or a lifespan shift from rate coding in children to temporal
      coding in adults.

PMID- 19840041
TI  - Inferring the size of a goal object from an actor's grasping movement in 6- and 9
      month-old infants.
AB  - The present study applied a preferential looking paradigm to test whether 6- and
      9-month old infants are able to infer the size of a goal object from an actor's
      grasping movement. The target object was a cup with the handle rotated either
      towards or away from the actor. In two experiments, infants saw the video of an
      actor's grasping movement towards an occluded target object. The aperture size of
      the actor's hand was varied as between-subjects factor. Subsequently, two final
      states of the grasping movement were presented simultaneously with the occluder
      being removed. In Experiment 1, the expected final state showed the actor's hand
      holding a cup in a way that would be expected after the performed grasping
      movement. In the unexpected final state, the actor's hand held the cup at the
      side which would be unexpected after the performed grasping movement. Results
      show that 6- as well as 9-month-olds looked longer at the unexpected than at the
      expected final state. Experiment 2 excluded an alternative explanation of these
      findings, namely that the discrimination of the final states was due to
      geometrical familiarity or novelty of the final states. These findings provide
      evidence that infants are able to infer the size of a goal object from the
      aperture size of the actor's hand during the grasp.

PMID- 19840042
TI  - Categorical flexibility in preschoolers: contributions of conceptual knowledge
      and executive control.
AB  - The current study evaluated the relative roles of conceptual knowledge and
      executive control on the development of categorical flexibility, the ability to
      switch between simultaneously available but conflicting categorical
      representations of an object. Experiment 1 assessed conceptual knowledge and
      executive control together; Experiment 2 differentiated conceptual knowledge from
      costly executive processes. In Experiment 1, 3- to 5-year-olds were given a three
      choice (taxonomic, thematic, and nonassociate) match-to-sample task and asked to
      match two associates. In Experiment 2, same-aged children were assessed on
      another match-to-sample task that reduced executive costs by presenting thematic
      and taxonomic associates on separate trials. By comparing performance across
      tasks, age-related changes resulting from conceptual knowledge and executive
      control indicated that conceptual knowledge of superordinate relations showed
      gains between 3 and 4 years, whereas gains in executive control were seen between
      4 and 5 years, suggesting a decalage in the development of conceptual and
      executive processes underlying categorical flexibility.

PMID- 19840043
TI  - Developmental shift in the discrimination of vowel contrasts in bilingual
      infants: is the distributional account all there is to it?
AB  - A shift from language-general to language-specific sound discrimination abilities
      has been largely attested in different populations of infants during the second
      half of the first year of life; however, data are still scarce regarding
      bilingual populations. Previous research with 4-, 8- and 12-month-old Catalan
      Spanish bilingual infants had offered evidence of a U-shaped pattern in their
      ability to discriminate a language-specific vowel contrast. This research
      explores monolingual and bilingual 4- and 8-month-olds' capacities to
      discriminate two common vowel contrasts: /o-u/ and /e-u/. All groups succeeded
      except 8-month-old bilinguals tested on the phonetically close /o-u/ contrast.
      Discrimination was not facilitated when talker and token variability were
      reduced. A U-shaped pattern was again found when data from an additional group of
      12-month-olds were included. These results confirm bilinguals' specific
      developmental pattern of perceptual reorganization for acoustically close vowels
      and challenge an interpretation merely based on a distributional account.

PMID- 19840045
TI  - Children's use of gesture to resolve lexical ambiguity.
AB  - We report on a study investigating 3-5-year-old children's use of gesture to
      resolve lexical ambiguity. Children were told three short stories that contained
      two homonym senses; for example, bat (flying mammal) and bat (sports equipment).
      They were then asked to re-tell these stories to a second experimenter. The data
      were coded for the means that children used during attempts at disambiguation:
      speech, gesture, or a combination of the two. The results indicated that the 3
      year-old children rarely disambiguated the two senses, mainly using deictic
      pointing gestures during attempts at disambiguation. In contrast, the 4-year-old
      children attempted to disambiguate the two senses more often, using a larger
      proportion of iconic gestures than the other children. The 5-year-old children
      used less iconic gestures than the 4-year-olds, but unlike the 3-year-olds, were
      able to disambiguate the senses through the verbal channel. The results highlight
      the value of gesture to the development of children's language and communication
      skills.

PMID- 19840044
TI  - Change in action: how infants learn to walk down slopes.
AB  - A critical aspect of perception-action coupling is the ability to modify ongoing
      actions in accordance with variations in the environment. Infants' ability to
      modify their gait patterns to walk down shallow and steep slopes was examined at
      three nested time scales. Across sessions, a microgenetic training design showed
      rapid improvements after the first session in infants receiving concentrated
      practice walking down slopes and in infants in a control group who were tested
      only at the beginning and end of the study. Within sessions, analyses across easy
      and challenging slope angles showed that infants used a 'braking strategy' to
      curb increases in walking speed across increasingly steeper slopes. Within
      trials, comparisons of infants' gait modifications before and after stepping over
      the brink of the slopes showed that the braking strategy was planned
      prospectively. Findings illustrate how observing change in action provides
      important insights into the process of skill acquisition.

PMID- 19840046
TI  - Language-specific stress perception by 9-month-old French and Spanish infants.
AB  - During the first year of life, infants begin to have difficulties perceiving non
      native vowel and consonant contrasts, thus adapting their perception to the
      phonetic categories of the target language. In this paper, we examine the
      perception of a non-segmental feature, i.e. stress. Previous research with adults
      has shown that speakers of French (a language with fixed stress) have great
      difficulties in perceiving stress contrasts (Dupoux, Pallier, Sebastian & Mehler,
      1997), whereas speakers of Spanish (a language with lexically contrastive stress)
      perceive these contrasts as accurately as segmental contrasts. We show that
      language-specific differences in the perception of stress likewise arise during
      the first year of life. Specifically, 9-month-old Spanish infants successfully
      distinguish between stress-initial and stress-final pseudo-words, while French
      infants of this age show no sign of discrimination. In a second experiment using
      multiple tokens of a single pseudo-word, French infants of the same age
      successfully discriminate between the two stress patterns, showing that they are
      able to perceive the acoustic correlates of stress. Their failure to discriminate
      stress patterns in the first experiment thus reflects an inability to process
      stress at an abstract, phonological level.

PMID- 19840047
TI  - Enumeration of objects and substances in non-human primates: experiments with
      brown lemurs (Eulemur fulvus).
AB  - Both human infants and adult non-human primates share the capacity to track small
      numbers of objects across time and occlusion. The question now facing
      developmental and comparative psychologists is whether similar mechanisms give
      rise to this capacity across the two populations. Here, we explore whether non
      human primates' object tracking abilities are subject to the same constraints as
      those of human infants. In particular, we examine whether one primate species,
      the brown lemur (Eulemur fulvus), also fails to represent and enumerate objects
      when they behave non-rigidly or non-cohesively. We presented lemurs with a series
      of expectancy violation studies involving simple 1 + 1 addition events in which
      we varied the entities to be enumerated. Like infants, lemurs successfully
      enumerated the two objects when those objects were rigid, cohesive individuals,
      but failed to enumerate similar-looking non-rigid piles of sand. In contrast to
      human infants, however, lemurs successfully enumerated non-cohesive objects that
      broke into multiple pieces. These results are discussed in light of recent
      theories about object processing in human infants and adults.

PMID- 19840048
TI  - Change of reference frame for tactile localization during child development.
AB  - Temporal order judgements (TOJ) for two tactile stimuli, one presented to the
      left and one to the right hand, are less precise when the hands are crossed over
      the midline than when the hands are uncrossed. This 'crossed hand' effect has
      been considered as evidence for a remapping of tactile input into an external
      reference frame. Since late, but not early, blind individuals show such
      remapping, it has been hypothesized that the use of an external reference frame
      develops during childhood. Five- to 10-year-old children were therefore tested
      with the tactile TOJ task, both with uncrossed and crossed hands. Overall
      performance in the TOJ task improved with age. While children older than 5 1/2
      years displayed a crossed hand effect, younger children did not. Therefore the
      use of an external reference frame for tactile, and possibly multisensory,
      localization seems to be acquired at age 5.

PMID- 19840049
TI  - 'Unwilling' versus 'unable': capuchin monkeys' (Cebus apella) understanding of
      human intentional action.
AB  - A sensitivity to the intentions behind human action is a crucial developmental
      achievement in infants. Is this intention reading ability a unique and relatively
      recent product of human evolution and culture, or does this capacity instead have
      roots in our non-human primate ancestors? Recent work by Call and colleagues
      (2004) lends credence to the latter hypothesis, providing evidence that
      chimpanzees are also sensitive to human intentions. Specifically, chimpanzees
      remained in a testing area longer and exhibited fewer frustration behaviors when
      an experimenter behaved as if he intended to give food but was unable to do so,
      than when the experimenter behaved as if he had no intention of giving food. The
      present research builds on and extends this paradigm, providing some of the first
      evidence of intention reading in a more distant primate relative, the capuchin
      monkey (Cebus apella). Like chimpanzees, capuchin monkeys distinguish between
      different goal-directed acts, vacating an enclosure sooner when an experimenter
      acts unwilling to give food than when she acts unable to give food. Additionally,
      we found that this pattern is specific to animate action, and does not obtain
      when the same actions are performed by inanimate rods instead of human hands (for
      a similar logic, see Woodward, 1998). Taken together with the previous evidence,
      the present research suggests that our own intention reading is not a wholly
      unique aspect of the human species, but rather is shared broadly across the
      primate order.

PMID- 19840050
TI  - Asymmetrical cortical processing of radial expansion/contraction in infants and
      adults.
AB  - We report asymmetrical cortical responses (steady-state visual evoked potentials)
      to radial expansion and contraction in human infants and adults. Forty-four
      infants (22 3-month-olds and 22 4-month-olds) and nine adults viewed dynamic dot
      patterns which cyclically (2.1 Hz) alternate between radial expansion (or
      contraction) and random directional motion. The first harmonic (F1) response in
      the steady-state VEP response must arise from mechanisms sensitive to the global
      radial motion structure. We compared F1 amplitudes between expansion-random and
      contraction-random motion alternations. F1 amplitudes for contraction were
      significantly larger than those for expansion for the older infants and adults
      but not for the younger infants. These results suggest that the human cortical
      motion mechanisms have asymmetrical sensitivity for radial expansion vs.
      contraction, which develops at around 4 months of age. The relation between
      development of sensitivity to radial motion and cortical motion mechanisms is
      discussed.

PMID- 19840051
TI  - Contribution of the priming paradigm to the understanding of the conceptual
      developmental shift from 5 to 9 years of age.
AB  - We conducted three experiments to study the role of instrumental (e.g. knife
      bread) and categorical (e.g. cake-bread) relations in the development of
      conceptual organization with a priming paradigm, by varying the nature of the
      task (naming--Experiment 1--or categorical decision--Experiments 2 and 3). The
      participants were 5-, 7- and 9-year-old children and adults. The results showed
      that on both types of task, adults and 9-year-old children presented instrumental
      and categorical priming effects, whereas 5-year-old children presented mainly
      instrumental priming effects, with categorical effects remaining marginal.
      Moreover, the magnitude of the instrumental priming effects decreased with age.
      Finally, the priming effects observed for 7-year-old children depended on the
      task, especially for the categorical effects. The theoretical implications of
      these results for our understanding of conceptual reorganization from 5 to 9
      years of age are discussed.

PMID- 19840052
TI  - How useful is executive control training? Age differences in near and far
      transfer of task-switching training.
AB  - Although executive functions can be improved by training, little is known about
      the extent to which these training-related benefits can be transferred to other
      tasks, or whether this transfer can be modulated by the type of training. This
      study investigated lifespan changes in near transfer of task-switching training
      to structurally similar tasks and its modulation by verbal self-instructions and
      variable training, as well as far transfer to structurally dissimilar 'executive'
      tasks and fluid intelligence. Three age groups (8-10; 18-26; 62-76 years of age)
      were examined in a pretest-training-posttest design. We found near transfer of
      task-switching training in all age groups, especially in children and older
      adults. Near transfer was enhanced in adults and impaired in children when
      training tasks were variable. We also found substantial far transfer to other
      executive tasks and fluid intelligence in all age groups, pointing to the
      transfer of relatively general executive control abilities after training.

PMID- 19840053
TI  - Object permanence and method of disappearance: looking measures further
      contradict reaching measures.
AB  - Piaget proposed that understanding permanency, understanding occlusion events,
      and forming mental representations were synonymous; however, accumulating
      evidence indicates that those concepts are not unified in development. Infants
      reach for endarkened objects at younger ages than for occluded objects, and
      infants' looking patterns suggest that they expect occluded objects to reappear
      at younger ages than they reach for them. We reaffirm the latter finding in 5- to
      6-month-olds and find similar responses to faded objects, but we fail to find
      that pattern in response to endarkened objects. This suggests that looking
      behavior and reaching behavior are both sensitive to method of disappearance, but
      with opposite effects. Current cognition-oriented (i.e. representation-oriented)
      explanations of looking behavior cannot easily accommodate these results; neither
      can perceptual-preference explanations, nor the traditional ecological
      reinterpretations of object permanence. A revised ecological hypothesis, invoking
      affordance learning, suggests how these differences could arise developmentally.

PMID- 19840054
TI  - Nap-dependent learning in infants.
AB  - Sleep has been shown to aid a variety of learning and memory processes in adults
      (Stickgold, 2005). Recently, we showed that infants' learning also benefits from
      subsequent sleep such that infants who nap are able to abstract the general
      grammatical pattern of a briefly presented artificial language (Gomez, Bootzin &
      Nadel, 2006). In the present study, we demonstrate, for the first time, long-term
      effects of sleep on memory for an artificial language. Fifteen-month-old infants
      who had napped within 4 hours of language exposure remembered the general
      grammatical pattern of the language 24 hours later. In contrast, infants who had
      not napped shortly after being familiarized with the language showed no evidence
      of remembering anything about the language. Our findings support the view that
      infants' frequent napping plays an essential role in establishing long-term
      memory.

PMID- 19840055
TI  - Sensitivity to communicative relevance tells young children what to imitate.
AB  - How do children decide which elements of an action demonstration are important to
      reproduce in the context of an imitation game? We tested whether selective
      imitation of a demonstrator's actions may be based on the same search for
      relevance that drives adult interpretation of ostensive communication. Three
      groups of 18-month-old infants were shown a toy animal either hopping or sliding
      (action style) into a toy house (action outcome), but the communicative relevance
      of the action style differed depending on the group. For the no prior information
      group, all the information in the demonstration was new and so equally relevant.
      However, for infants in the ostensive prior information group, the potential
      action outcome was already communicated to the infant prior to the main
      demonstration, rendering the action style more relevant. Infants in the ostensive
      prior information group imitated the action style significantly more than infants
      in the no prior information group, suggesting that the relevance manipulation
      modulated their interpretation of the action demonstration. A further condition
      (non-ostensive prior information) confirmed that this sensitivity to new
      information is only present when the 'old' information had been communicated, and
      not when infants discovered this information for themselves. These results
      indicate that, like adults, human infants expect communication to contain
      relevant content, and imitate action elements that, relative to their current
      knowledge state or to the common ground with the demonstrator, is identified as
      most relevant.

PMID- 19840056
TI  - Sequence learning in infancy: the independent contributions of conditional
      probability and pair frequency information.
AB  - The ability to perceive sequences is fundamental to cognition. Previous studies
      have shown that infants can learn visual sequences as early as 2 months of age
      and it has been suggested that this ability is mediated by sensitivity to
      conditional probability information. Typically, conditional probability
      information has covaried with frequency information in these studies, raising the
      possibility that each type of information may have contributed independently to
      sequence learning. The current study explicitly investigated the independent
      contribution of each type of information. We habituated 2.5-, 4.5-, and 8.5-month
      old infants to a sequence of looming visual shapes whose ordering was defined
      independently by specific conditional probability relations among pair elements
      and by the frequency of occurrence of such pairs. During test trials, we tested
      infants' sensitivity to each type of information and found that both types of
      information independently influenced sequence learning by 4.5 months of age.

PMID- 19840057
TI  - Age-related changes in the control of episodic retrieval: an ERP study of
      recognition memory in children and adults.
AB  - We examined developmental aspects of the ability to monitor the temporal context
      of an item's previous occurrence while event-related potentials (ERPs) were
      recorded. In a continuous recognition task, children between 10 and 12 years and
      young adults watched a stream of pictures repeated with a lag of 10-15
      intervening items and indicated recurrences. In a second run, these already
      familiar pictures were repeated as non-targets along with new pictures, while
      subjects were instructed to indicate only recurrences within the run. Young
      adults were able to maintain high performance levels in both tasks, whereas
      children had longer response times and committed a large number of false alarms
      to non-targets. ERPs in both age groups showed similar parietal old/new effects
      for target repetitions within runs. In addition, adults' ERPs showed similar
      old/new effects at frontal electrodes for repetitions and non-targets, presumably
      reflecting assessments of familiarity, whereas for children repeated relative to
      first presentations were associated with more negative-going waveforms at
      anterior frontal recording sites. Together, these results suggest a continuing
      maturation of the brain networks assessing novelty or familiarity. Recollection
      as indexed by parietal old/new effects appeared similar between young adults and
      children, but the development of controlled episodic retrieval, resulting in
      recollection of non-target information, appears to continue well into
      adolescence.

PMID- 19840058
TI  - Genetic architecture of verbal abilities in children and adolescents.
AB  - The etiology of individual differences in general verbal ability, verbal learning
      and letter and category fluency were examined in two independent samples of 9-
      and 18-year-old twin pairs and their siblings. In both age groups, we observed
      strong familial resemblance for general verbal ability and moderate familial
      resemblance for verbal learning, letter and category fluency. All familial
      resemblance was explained by genetic factors. There was significant covariance
      among the tests, which was stronger in magnitude in the adolescent cohort. The
      covariance was mainly explained by genetic effects shared by subtests, both in
      middle childhood and in late adolescence. In addition to a shared set of genes
      that influenced all phenotypes, there were also genetic influences specific to
      the different verbal phenotypes.

PMID- 19840060
TI  - Relationship between manual preferences for object manipulation and pointing
      gestures in infants and toddlers.
AB  - The aim of this study was to measure the pattern of hand preferences for pointing
      gestures as a function of object-manipulation handedness in 123 infants and
      toddlers (10-40 months). The results showed that not only right-handers but also
      left-handers and ambidextrous participants tended to use their right hand for
      pointing. There was a significant correlation between manual preferences and
      pointing lateralization. Further analyses showed that the correlation between
      these two indexes was at its strongest during two key phases of language
      development (i.e. vocabulary spurt and syntax improvement) and weakened to become
      nonsignificant in the interim. These findings support the view that humans have a
      specialized area for communicative gestures and language in the left cerebral
      hemisphere that may be independent of the system controlling the purely motor
      functions of hand use.

PMID- 19840059
TI  - Developmental differences in memory for cross-modal associations.
AB  - Associative learning is critical to normal cognitive development in children.
      However, young adults typically outperform children on paired-associate tasks
      involving visual, verbal and spatial location stimuli. The present experiment
      investigated cross-modal odour-place associative memory in children (7-10 years)
      and young adults (18-24 years). During the study phase, six odours were
      individually presented and paired with one of 12 spatial locations on a board.
      During the test phase, participants were presented with the six stimuli
      individually and were asked to place each stimulus on the correct spatial
      location. Children committed significantly more errors on the odour-place task
      than did young adults. However, item recognition memory for the odours or spatial
      locations involved in the odour-place associative memory task was similar between
      children and young adults. Therefore, poor odour-place associative memory in
      children did not result from impaired memory for the individual odours or spatial
      locations involved in the associations. The results suggest that cross-modal
      associative memory is not fully developed in children.

PMID- 19840061
TI  - How do symbols affect 3- to 4-year-olds' executive function? Evidence from a
      reverse-contingency task.
AB  - In two experiments, 330 3- to 4-year-olds competed for stickers in a game in
      which the optimal response strategy was to point to an empty box that their
      opponent would receive in order to obtain a baited box for themselves. When the
      baited box contained stickers, children showed a strong tendency to point at the
      baited box and therefore lose the stickers to their opponent. In Experiment 1
      children performed better when the number of stickers to be won was represented
      with one of five different types of symbol: numerals, number words, dots, a
      photograph or sweets. In Experiment 2 children transferred their improved
      performance in symbolic conditions to non-symbolic conditions. These findings
      suggest that symbols enable children to formulate an efficient response strategy,
      and that this effect may be qualitatively different in children from the effect
      of symbols in non-human primates.

PMID- 19840062
TI  - Why is visual search superior in autism spectrum disorder?
AB  - This study investigated the possibility that enhanced memory for rejected
      distractor locations underlies the superior visual search skills exhibited by
      individuals with autism spectrum disorder (ASD). We compared the performance of
      21 children with ASD and 21 age- and IQ-matched typically developing (TD)
      children in a standard static search task and a dynamic search task, in which
      targets and distractors randomly changed locations every 500 ms, precluding the
      use of memory in search. Children with ASD exhibited overall faster reaction time
      (RT) relative to TD children, and showed no disruption in search efficiency in
      the dynamic condition, discounting the possibility that memory for rejected
      distractors augments their visual search abilities. Analyses of RT x set size
      functions showed no group differences in slopes but lower intercepts for the ASD
      group in both static and dynamic search, suggesting that the ASD advantage
      derived from non-search processes, such as an enhanced ability to discriminate
      between targets and distractors at the locus of attention. Eye-movement analyses
      revealed that the ASD and TD groups were similar in the number and spatial
      distribution of fixations across the search array, but that fixation duration was
      significantly shorter among children with ASD. Lower intercepts in static search
      were related to increased symptom severity in children with ASD. In summary, ASD
      search superiority did not derive from differences in the manner in which
      individuals with ASD deployed their attention while searching, but from
      anomalously enhanced perception of stimulus features, which was in turn
      positively associated with autism symptom severity.

PMID- 19840063
TI  - The effects of Xanthigen in the weight management of obese premenopausal women
      with non-alcoholic fatty liver disease and normal liver fat.
AB  - AIM: To investigate the effects of Xanthigen (brown marine algae fucoxanthin +
      pomegranate seed oil (PSO)) on body weight, body fat, liver lipids, and blood
      biochemistry; and Xanthigen and its individual components on resting energy
      expenditure (REE) in obese, non-diabetic female volunteers with non-alcoholic
      fatty liver disease (NAFLD) and normal liver fat (NLF) content. METHODS: Sixteen
      week, double-blind, randomized, placebo-controlled study. Food record data, body
      composition, REE (only 41 volunteers with NAFLD) and blood sample analysis were
      assessed weekly for 16 weeks in 151 non-diabetic, obese premenopausal women with
      liver fat content above 11% (NAFLD) n = 113, and below 6.5% (NLF) n = 38.
      RESULTS: Xanthigen-600/2.4 mg (300 mg PSO + 300 mg brown seaweed extract
      containing 2.4 mg fucoxanthin) resulted in statistically significant reduction of
      body weight (5.5 +/- 1.4 kg NAFLD group and 4.9 +/- 1.2 kg NLF group, p < 0.05),
      waist circumference (NAFLD group only), body (3.5 +/- 1.9 kg NAFLD group, p <
      0.001; 3.6 +/- 0.7 kg NLF group, p < 0.05) and liver fat content, liver enzymes
      (NAFLD group only), serum triglycerides and C-reactive protein. Weight loss and
      reduction in body and liver fat content occurred earlier in patients with NLF
      than in patients with NAFLD. Fucoxanthin (> 2.4 mg) and Xanthigen-400/1.6 mg (200
      mg PSO + 200 mg brown seaweed extract containing 1.6 mg fucoxanthin)
      significantly increased REE in NAFLD subjects compared to placebo. CONCLUSIONS:
      Xanthigen promoted weight loss, reduced body and liver fat content, and improved
      liver function tests in obese non-diabetic women. Xanthigen and Fucoxanthin also
      increased REE. This product may be considered a promising food supplement in the
      management of obesity.

PMID- 19840068
TI  - Left ventricular end-systolic stress in young adults: distribution, risk factors,
      and relation to cardiovascular disease events.
AB  - BACKGROUND: We examined the relationship of left ventricular (LV) end-systolic
      meridional wall stress (LVESS), a measure of LV afterload, with race, gender,
      other cardiovascular risk factors and LV mass in 3,994 young adults in the
      Coronary Artery Risk Development in Young Adults (CARDIA) Study. METHODS: From
      transthoracic echocardiography, LVESS was derived from LV internal dimension and
      posterior wall thickness and systolic blood pressure (BP). RESULTS: Adjusted
      LVESS was significantly greater in black men versus women (59.0 vs. 54.8
      dynes/cm, P < 0.01) and in white men versus women (59.0 vs. 55.4 dynes/cm(2), P <
      0.01), but did not differ in comparing whites versus blacks either in men or
      women. In multiple regression analyses, age and LV mass were inversely (P < 0.01)
      and height was positively (P < 0.01) associated with LVESS. The overall variance
      of LVESS explained by the models in each race-sex subgroup was low (R(2) less
      than 0.03), suggesting that standard risk factors contribute little to
      determining LVESS in young adults. Over a 15-year follow-up period, LVESS, after
      the adjustment for covarieties, was not associated with the incidence of coronary
      heart disease (CHD) and cardiovascular disease (CVD) events. CONCLUSION: LVESS
      may not be a useful marker of cardiovascular risk in young adults; further study
      is needed to determine whether other echocardiographic measures may be more
      useful predictors.

PMID- 19840067
TI  - Discrepancy between gradients derived by cardiac catheterization and by Doppler
      echocardiography in aortic stenosis: how often does pressure recovery play a
      role?
AB  - Studies have shown very good correlation between Doppler-derived gradients and
      gradients obtained by cardiac catheterization (cath) in aortic stenosis (AS).
      However, the phenomenon of pressure recovery may lead to significant
      overestimation of aortic valve (AV) gradients by Doppler echocardiography (echo).
      We hypothesized that echo-derived gradients will be higher in mild-moderate AS
      because of pressure recovery. We studied 94 patients who had echo and cardiac
      caths in a span of 1 week. The mean age was 72 +/- 13 years, 54% males, 79% had
      coronary artery disease, and the mean left ventricular ejection fraction was 45
      +/- 22%. The mean cardiac output and cardiac indices were 5.1 +/- 1.4/2.7 +/- 0.6
      (l/mt), (l/m(2)), respectively. For those with mild AS, echo overestimated
      gradients in 9.5% of patients (4/42) by an average of 19 mmHg, thus
      misclassifying the degree of stenosis. In those with moderate AS, 14% (3/21) were
      misclassified as severe AS (gradient overestimation by an average of 13.6 mmHg).
      In those with severe AS, echo underestimated gradients in 13% (4/31) by an
      average of 22.7 mmHg. The aorta at the sinotubular junction was 2.8 cm in those
      patients with mild AS in whom gradients were overestimated by more than 20 mmHg
      compared to a sinotubular junction diameter of 3.12 cm in those with mild AS and
      no overestimation of gradients. The AV area/aortic root ratio was 0.4 in those
      with mild AS and 0.2 in those with severe AS (P < 0.05).

PMID- 19840069
TI  - Early diagnosis of right ventricular systolic dysfunction by tissue Doppler
      derived isovolumic myocardial acceleration in patients with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVES: The aim of the study was to assess validity of tissue Doppler imaging
      (TDI)-derived right ventricular (RV) myocardial systolic velocities in early
      detection of RV systolic dysfunction in chronic obstructive pulmonary disease
      (COPD). METHODS: Ninety COPD patients (50 pure COPD and 40 with right heart
      failure [RHF]) and 40 controls were enrolled. Respiratory function tests,
      conventional echocardiographic parameters, and TDI-derived isovolumic myocardial
      acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV),
      peak velocity during systolic ejection (Sa) were measured. RESULTS: All the TDI
      derived RV systolic velocities were impaired in COPD (P = 0.0001) compared to
      controls. IVA was the only parameter that could distinguish the patients with
      pure COPD and COPD with RHF (P = 0.0001). IVA was found to be significantly
      correlated with FEV1 (r = 0.41, P = 0.0001), FEV1/FVC (r = 0.43, P = 0.0001),
      pulmonary artery pressure (r =-0.34, P = 0.001), pulmonary flow acceleration time
      (r = 0.48, P = 0.0001), and tricuspid annular systolic excursion (r =-0.41, P =
      0.0001). In addition, IVA < or = 2.7 m/sec(2) was able to predict COPD patients
      from controls with 81% sensitivity, 98% specificity and IVA < or = 1.9 m/sec(2)
      predicted COPD patients accompanied by RHF with 82% sensitivity, 77% specificity
      from patients without RHF. CONCLUSIONS: TDI-derived RV IVA is a novel,
      noninvasive echocardiographic index which may be used in the assessment of
      subclinical RV dysfunction in patients with COPD.

PMID- 19840070
TI  - Usefulness of the evaluation of isovolumic and ejection phase myocardial signals
      during stress echocardiography in predicting exercise capacity in heart failure
      patients.
AB  - AIM: To assess changes of systolic function using tissue Doppler imaging (TDI)
      during stress echocardiography and its impact on exercise capacity in heart
      failure (HF) patients (pts). MATERIAL AND METHODS: 80 pts (65 male), mean age of
      59.3 +/- 10.9 years, NYHA class 1.95 +/- 0.8, left ventricle ejection fraction
      (LVEF) 27.2 +/- 9.5 (10-45%). The etiology of HF was ischemic (ICM) in 50 pts and
      dilated cardiomyopathy (DCM) in 30 pts. Peak myocardial velocity (IVV) and
      acceleration (IVA) during isovolumic contraction and peak myocardial velocity
      during ejection phase (S') were measured at baseline and peak exercise during
      semi-supine stress-echo (20 Watts, 2-min increments). Concurrently peak oxygen
      uptake (VO(2) peak) was measured. RESULTS: Rest values of analyzed parameters
      were comparable in groups according to etiology of HF and physical capacity.
      However, peak stress parameters mainly S' were significantly higher in the DCM
      group and the group with better VO(2) peak. The best correlation with exercise
      capacity was S' at peak stress (r = 0.66; p < 0.0001). The most useful parameter
      for identifying severe exercise intolerance, VO(2) peak < 14 ml/kg/min, was S'
      with an area under ROC curve of 0.82 +/- 0.05 (95% CI 0.71-0.89). The cutoff of
      5.75 cm/s for S' at peak stress showed a sensitivity of 61% with a specificity of
      96%. CONCLUSIONS: The evaluation of systolic function by means of TDI instead of
      LVEF shows more clearly that systolic function is at least partly responsible for
      exercise tolerance in HF. Assessment of echocardiographic systolic parameters at
      peak stress provides more accurate information about exercise capacity in HF pts.

PMID- 19840071
TI  - The Marfan syndrome: implications for athletes and their echocardiographic
      assessment.
AB  - Sudden death of competitive athletes is rare. These deaths challenge the
      perception that trained athletes represent the healthiest segment of modern
      society. The increasing frequency of such reported deaths worldwide and the
      visibility of the issue is underlined by the high-profile nature of each case.
      The majority of these deaths have been due to a variety of undiagnosed
      cardiovascular diseases. Marfan syndrome is a heritable disorder of the
      connective tissue that can hold life threatening consequences, especially for the
      athletic population. This paper will aim to review cardiovascular pathophysiology
      and assessment in relation to Marfan syndrome with particular reference to
      echocardiography and the athletic population.

PMID- 19840072
TI  - Liquefaction necrosis of calcified mitral annulus.
AB  - Echogenicity within the left atrioventricular groove can be due to many
      conditions, such as mitral annular calcification, abscess, dilated coronary
      sinus, and aneurysm of the left circumflex coronary artery. However, in a patient
      who has no systemic symptoms, a bright, round echodensity with central
      echolucency and smooth borders in the mitral annulus is characteristic of
      liquefaction necrosis of a calcified mitral annulus. We report the occurrence of
      this rare manifestation in a 60-year-old patient who presented with myocardial
      infarction.

PMID- 19840073
TI  - Penetrating atherosclerotic aortic ulcer mimicking acute inferior myocardial
      infarction.
AB  - Penetrating atherosclerotic ulcers (PAU), aortic dissection, and intramural
      hematoma are the three most important diseases involving the aorta which are
      classified as acute aortic syndromes. Penetrating atherosclerotic aortic
      ulceration is characterized by ulceration of atheromatous plaque disrupting the
      internal elastic lamina. These aortic ulcers may penetrate through the media to
      cause aortic pseudoaneurysms or less often through the adventitia to cause
      transmural aortic rupture. We described a case of penetrating atherosclerotic
      ulcer of ascending aorta mimicking ST elevation myocardial infarction. To our
      knowledge, this is the first case reported in the literature of such a
      complication from PAU.

PMID- 19840074
TI  - 2D and 3D echocardiography of a left ventricular diverticulum.
AB  - A real time transthoracic 3D study of a left ventricular diverticulum established
      through a narrow orifice located between the aortic and mitral valves is
      presented. Diverticular morphology was reconstructed and its volumes were
      calculated by this technique for the first time in the literature.

PMID- 19840075
TI  - Evaluation of a posterior mitral valve leaflet aneurysm by real time three
      dimensional transesophageal echocardiography.
AB  - Posterior mitral valve (MV) leaflet aneurysms are extremely rare complications of
      infective endocarditis (IE). When MV aneurysms occur, they usually involve the
      anterior leaflet. Real time three-dimensional transesophageal echocardiography
      (RT3D TEE) has been recently developed and provides views of unparalleled quality
      by optimizing visualization of spatial relationships. We present a rare case of a
      posterior MV leaflet aneurysm due to IE in a 64-year-old woman, best visualized
      by RT3D TEE.

PMID- 19840076
TI  - Transesophageal real time three-dimensional echocardiography in assessment of
      partial atrioventricular septal defect.
AB  - We present a practical application of real time three-dimensional transesophageal
      echocardiography in a 67-year-old male patient with congenital heart disease.

PMID- 19840077
TI  - Live/real time three-dimensional transthoracic echocardiographic assessment of
      transposition of the great arteries in the adult.
AB  - We studied 11 adult patients with dextro-transposition and 5 adult patients with
      levo-transposition (corrected transposition) of the great arteries with real time
      two-dimensional (2DTTE) and live/real time three-dimensional transthoracic
      echocardiography (3DTTE). All patients with dextro-transposition underwent a
      Mustard or Senning procedure during infancy. Incremental findings provided by
      3DTTE and not delineated by 2DTTE were (a) comprehensive examination of all three
      leaflets of the tricuspid valve including the detection and measurement of
      anatomic defects in the leaflets and the assessment of systolic noncoaptation and
      segmental prolapse; (b) en face viewing and measurement of vena contracta areas
      of the valvular regurgitation jets and the assessment of regurgitant volumes; (c)
      en face viewing of the intra-atrial baffle and localization and measurement of
      baffle defects as well as the measurement of vena contractas of the baffle leaks;
      (d) recognition of a bicuspid pulmonary valve; and (e) the quantitative
      assessment of left ventricular outflow tract obstruction. 3DTTE appears to be a
      useful noninvasive modality which could supplement 2DTTE in the comprehensive
      assessment of adult patients with transposition of the great arteries.

PMID- 19840079
TI  - An unusual presentation of diaphragmatic hernia.

PMID- 19840078
TI  - Paraprosthetic leak unmasked by combined enoxaparin/warfarin therapy for
      thrombosed mitral valve.

PMID- 19840080
TI  - Normal anatomic variants on transthoracic echocardiogram.
AB  - Apart from their existence as medical curiosities, anatomic variants also double
      as diagnostic dilemmas. In the heart, more than in any other location in the
      body, misinterpretation of normal anatomic variants as pathologic entities can
      have a profound impact on treatment decisions and clinical consequences.
      Echocardiography is an easily accessible tool these days and is used routinely in
      most cardiac evaluations. Thus it becomes imperative for the echocardiographer to
      be cognizant of normal anatomic variants. Furthermore, echocardiographic findings
      should always be evaluated in their proper clinical context and diagnoses should
      never be entertained in a clinical vacuum. The literature is replete with
      numerous case reports and vignettes on these fascinating structures but is
      lacking in a formal review of normal anatomic variants. In this article, we have
      attempted a systemic review of normal variants, their embryologic origins,
      echocardiographic characteristics, and common pitfalls encountered in their
      evaluation.

PMID- 19840081
TI  - Congenitally corrected transposition of the great arteries (CCTGA) initially
      presenting in the sixth decade.
AB  - Adult congenital heart disease (ACHD) has become increasingly important in adult
      cardiology. A 54-year-old female presented with symptoms and signs of new onset
      heart failure. Echocardiography showed congenitally corrected transposition of
      the great arteries (CCTGA) with systolic dysfunction of the systemic right
      ventricle, ejection fraction was 15 to 20% and no other associated abnormalities.
      CCTGA is often missed in cardiology practice due to failure to recognize the
      abnormal position of the ventricles and the associated AV valves. One percent of
      patients with CCTGA are uncomplicated without VSD, PS or Ebstein's anomaly of the
      systemic AV valve; this was the case for our patient. Most patients present in
      early adulthood. The mechanism of systemic ventricular failure has been related
      to fibrosis due to oxygen supply and demand mismatch.

PMID- 19840082
TI  - The relative roles of kinship and reciprocity in explaining primate altruism.
AB  - Several hypotheses have been proposed to explain the evolution of altruistic
      behaviours. Their relative roles in explaining actual cases of animal altruism
      are, however, unclear. In particular, while kin selection is widely believed to
      have a pervasive influence on animal behaviour, reciprocity is generally thought
      to be rare. Despite this general agreement, there has been no direct test
      comparing the relative roles of kinship and reciprocity in explaining animal
      altruism. In this paper, we report on the results of such a test based on a meta
      analysis of allogrooming in primates, grooming being probably the most common
      altruistic behaviour among mammals. In direct contrast to the prevailing view,
      reciprocity played a much larger role than kinship in explaining primate
      allogrooming. These results point to a more significant role of reciprocity in
      the evolution of animal altruism than is generally acknowledged.

PMID- 19840083
TI  - Developments in international emergency medicine.

PMID- 19840084
TI  - Review article: Convulsive and non-convulsive status epilepticus: an emergency
      medicine perspective.
AB  - Status epilepticus (SE) is divided into convulsive and non-convulsive types; both
      are associated with significant morbidity and mortality. Although convulsive SE
      is easily recognized, non-convulsive SE remains an elusive diagnosis as physical
      signs are varied and subtle. Successful management depends on a comprehensive
      approach that involves diagnostic testing and pharmacological interventions while
      ensuring cerebral oxygenation and perfusion at all times. There are a limited
      number of well-designed studies to support the development of evidence-based
      recommendations for the management of SE, especially for the management of non
      convulsive status. Benzodiazepines, specifically lorazepam, continue to be the
      most commonly recommended first-line therapy; best treatment for refractory
      status cases depends on resources available and must be tailored to the
      individual institution. In order to facilitate care, it is recommended that each
      institution develop a management protocol for these patients.

PMID- 19840085
TI  - International Federation for Emergency Medicine model curriculum for medical
      student education in emergency medicine.
AB  - There is a critical and growing need for emergency physicians and emergency
      medicine resources worldwide. To meet this need, physicians must be trained to
      deliver time-sensitive interventions and life-saving emergency care. Currently,
      there is no internationally recognized, standard curriculum that defines the
      basic minimum standards for emergency medicine education. To address this lack,
      the International Federation for Emergency Medicine (IFEM) convened a committee
      of international physicians, health professionals and other experts in emergency
      medicine and international emergency medicine development, to outline a
      curriculum for foundation training of medical students in emergency medicine.
      This curriculum document represents the consensus of recommendations by this
      committee. The curriculum is designed with a focus on the basic minimum emergency
      medicine educational content that any medical school should be delivering to its
      students during their undergraduate years of training. It is designed, not to be
      prescriptive, but to assist educators and emergency medicine leadership in
      advancing physician education in basic emergency medicine content. The content
      would be relevant, not just for communities with mature emergency medicine
      systems, but also for developing nations or for nations seeking to expand
      emergency medicine within current educational structures. We anticipate that
      there will be wide variability in how this curriculum is implemented and taught,
      reflecting the existing educational milieu, the resources available, and the
      goals of the institutions' educational leadership.

PMID- 19840086
TI  - Challenges associated with electronic ordering in the emergency department: a
      study of doctors' experiences.
AB  - PURPOSE: The objective of the present study was to identify and report on the key
      challenges confronted by emergency doctors following the introduction of
      Computerised Provider Order Entry system in a major metropolitan hospital in
      Sydney. BASIC PROCEDURES: A qualitative study was undertaken during the period
      May 2006 to December 2006. The study included a series of eight interviews with
      three senior doctors and one focus group involving six registrars. Participants
      were chosen on the basis of their experience of planning for, or working with the
      new electronic ordering system. The study also incorporated five observation
      sessions and document analysis. Data were analysed iteratively, which led to the
      identification and elaboration of issues relevant to the research question.
      FINDINGS: Three major issues emerged from the findings: (i) the implementation of
      the new system was accompanied by major shifts in ED work responsibilities and
      tasks; (ii) the appearance of dysfunctional consequences of the new system
      related to the excess time it took to electronically order and the usability of
      some features of the new system; and (iii) doctors' concerns that their views and
      opinions about the design and implementation of the new system had not been
      adequately addressed. CONCLUSION: The implementation of electronic ordering has
      important implications for ED functioning and the delivery of patient care. The
      complexity of the ED makes it vulnerable to disruption caused by inadequate
      system design and ineffective channels of communication across the hospital.

PMID- 19840087
TI  - Prevalence of advance care directives in aged care facilities of the Northern
      Illawarra.
AB  - OBJECTIVE: To assess the prevalence of advance care directives in the residential
      aged care facilities within the catchment for a single ED and to assess the
      systems in place for development of those advance care directives with focus on
      documentation and communication. METHODS: A de-identified, paper-based, mail-out
      survey of all 30 residential aged care facilities potentially referring to the
      Wollongong Hospital ED. RESULTS: A total of 24 of 30 surveys were returned.
      Thirteen facilities reported at least some proportion of their residents having
      documented advance care directives. The median prevalence of advance care
      directives was 5% of residents (interquartile range 0-10%). Discussions with
      residents over advance care directives were reported in 9 of 24 survey returns.
      Not all facilities that reported documenting advance care directives had
      processes for regular review or 24 h access to the documentation for carers. Ten
      of the survey returns reported general practitioner involvement in advance care
      directive development. CONCLUSION: The facilities surveyed reported that advance
      care directives are the exception rather than the rule. Where they were developed
      some facilities did not ensure regular review, dissemination of the information
      nor consistent involvement of the GP. This demonstrates low utilization and poor
      application, which has implications for care appropriate to patients' wishes and
      for resource use within the ED.

PMID- 19840088
TI  - Malnutrition associated with increased risk of frail mechanical falls among older
      people presenting to an emergency department.
AB  - OBJECTIVE: To identify associations between malnutrition falls risk and hospital
      admission among older people presenting to ED. METHODS: A prospective convenience
      sample of patients, aged 60 years or more, presenting to an Australian tertiary
      teaching hospital ED were included in this cross-sectional study. Malnutrition
      Screening Tool and Subjective Global Assessment tool were administered to 126 non
      consecutive participants. Participants were categorized as non-fallers, frail
      mechanical or active mechanical fallers. Self-reported falls in past 6 months and
      hospital admission were documented. RESULTS: Participant age and sex (median age
      74, interquartile range 65-82 years; male 59%, 74/126, 95% CI 50-67%) were
      representative of older people presenting to the ED. Malnutrition prevalence was
      15% (19/126, 95% CI 9-21%). There was an increased risk of being assessed as
      malnourished when a frail mechanical faller relative to: a non-faller (relative
      risk [RR]: 1.5, 95% CI 1.0-2.3, P= 0.001), an active mechanical faller (RR: 3.1,
      95% CI 1.0-10.9, Fisher's Exact test P= 0.02) or a non-faller and active
      mechanical faller combined (RR: 1.5, 95% CI 1.0-2.1, P= 0.001). Malnourished
      participants had an increased risk of self-reported falls over 6 months (RR: 1.5,
      95% CI 1.0-2.5, P= 0.03). There was over five times the risk of hospital
      admission if malnourished than if well-nourished (RR: 5.3, 95% CI 1.4-20.0,
      Fisher's exact test P= 0.001). The Malnutrition Screening Tool captured 84%
      (16/19, 95% CI 78-92%) of participants assessed as malnourished by Subjective
      Global Assessment. CONCLUSIONS: Older people presenting to ED should be
      nutritionally screened. Malnutrition prevalence of 15% was documented and was
      associated with an increased risk of frail mechanical falls and hospital
      admission. The Malnutrition Screening Tool was a simple and practical screen for
      ED.

PMID- 19840089
TI  - Intranasal fentanyl in 1-3-year-olds: a prospective study of the effectiveness of
      intranasal fentanyl as acute analgesia.
AB  - The primary objective of the present study was to determine the effectiveness of
      intranasal fentanyl analgesia in children aged 1-3 years with acute moderate to
      severe pain presenting to the ED. We also aimed to gather information on the
      safety and acceptability of intranasal fentanyl in this age group. Two paediatric
      ED enrolled children aged 1-3 years, with acute moderate or severe pain.
      Intranasal fentanyl was administered (1.5 microg/kg) via a mucosal atomiser
      device using a 50 microg/mL solution of fentanyl. Physiological parameters (heart
      rate, respiratory rate, oxygen saturations and level of consciousness) were
      measured at regular intervals. Objective pain assessment was completed using the
      Faces, Legs, Arms, Cry, Consolability (FLACC) score. Forty-six children
      presenting with acute moderate to severe pain were included. The median FLACC
      score before intranasal fentanyl administration was 8 (interquartile range [IQR]
      5-10), decreasing to 2 (IQR 0-4) 10 min post fentanyl (P < 0.0001) and 0 (IQR 0
      2) 30 min post fentanyl (P < 0.0001). A clinically significant decrease in FLACC
      scores was seen in 93% of children 10 min post fentanyl administration and 98% of
      children 30 min post fentanyl. Intranasal fentanyl delivery using a mucosal
      atomiser was well tolerated by all children. There were no adverse drug reactions
      or adverse events detected. Intranasal fentanyl is an effective, safe and well
      tolerated mode of analgesia for children aged 1-3 years with moderate to severe
      pain.

PMID- 19840090
TI  - Knowledge and attitude towards paediatric cardiopulmonary resuscitation among the
      carers of patients attending the Emergency Department of the Children's Hospital
      at Westmead.
AB  - The present study aimed to describe the knowledge and attitudes of parents and
      carers in performing cardiopulmonary resuscitation on infants and children. A
      self-administered questionnaire distributed to a convenience sample of parents
      and carers attending the Emergency Department of The Children's Hospital at
      Westmead, Australia from February to March 2008. Main outcome measures were the
      prevalence of previous cardiopulmonary resuscitation training, willingness and
      confidence to perform cardiopulmonary resuscitation on infants and children
      compared with adults, and an objective assessment of knowledge of current
      resuscitation guidelines. A total of 348 parents and carers were surveyed; 53%
      had received previous cardiopulmonary resuscitation training, 75% prior to the
      previous year. There was no significant difference on their willingness to
      perform cardiopulmonary resuscitation on an adult versus a child (75.6% and 75.8%
      respectively, P= 0.870). However, 81% were willing to perform cardiopulmonary
      resuscitation on a relative whereas only 64% were willing to perform
      cardiopulmonary resuscitation on a stranger (P < 0.001). Respondents were
      moderately confident in delivering cardiopulmonary resuscitation to a collapsed
      child; mean score of 2.9 on 5-point Likert scale. Only 11% of respondents knew
      the correct rate for chest compressions and the ratio of compressions to
      ventilations; 8% had performed cardiopulmonary resuscitation in a real situation.
      Parents and carers are willing to perform cardiopulmonary resuscitation,
      especially on family members. However, their knowledge of the current guidelines
      was poor. More public education is required to update those with previous
      training and to encourage those who haven't to be trained.

PMID- 19840091
TI  - Pyloric stenosis: a retrospective study of an Australian population.
AB  - Increased awareness of idiopathic hypertrophic pyloric stenosis (IHPS) and
      readily available ultrasonographic diagnosis might mean that 'classic'
      presentations are becoming less common. We sought to describe the epidemiology,
      clinical features and outcomes of children with IHPS in the modern era. A
      retrospective case review of all cases of IHPS presenting to a single tertiary
      paediatric hospital over an 11 year period was conducted. Inclusion criteria were
      met by 329 children with confirmed IHPS. Eighty-four per cent of patients were
      male and 19% were born premature. Premature infants tended to present later,
      reflecting postmenstrual age. The median age at presentation was 5 weeks (range 0
      31) with median symptom duration of 7 days (range 1-95). At least one classic
      symptom or sign was present in 87% of infants but only 14% had the classic triad
      (projectile vomiting, palpable olive and visible peristalsis). Elevated
      bicarbonate was present in 61% of blood samples, whereas hypochloraemia was found
      in only 29%. Ultrasound confirmed the diagnosis in 89%. Surgical techniques were
      similar in outcome, except that incomplete pyloromyotomy was more common with the
      laparoscopic compared with periumbilical approach (6% vs 1%, P= 0.023). IHPS
      occurs more frequently in male and ex-premature infants. It commonly presents
      without the full spectrum of 'classic' symptoms and signs. Given the availability
      of ultrasound diagnosis, IHPS should be considered in all babies with any one of
      the classic findings.

PMID- 19840092
TI  - Paediatric emergency medicine in the developing world: The Queen Elizabeth
      Central Hospital, Blantyre, Malawi.
AB  - Malawi is a small, landlocked country in Southern Africa and is one of the
      poorest countries in the world. Life expectancy, infant and under five mortality
      statistics are appalling relative to the developed world. This article describes
      the experience of an emergency physician from Australia in a Paediatric Accident
      and Emergency department in Blantyre, Malawi.

PMID- 19840093
TI  - Differential diagnosis of pneumoperitoneum caused by liposuction abdominoplasty.

PMID- 19840094
TI  - Os vesalianum pedis misdiagnosed as fifth metatarsal avulsion fracture.

PMID- 19840101
TI  - Halophilic Archaea cultured from ancient halite, Death Valley, California.
AB  - Halophilic Archaea cultured from ancient fluid inclusions in a 90-m-long (0- to
      100,000-year-old) salt core from Death Valley, California, demonstrate survival
      of bacterial cells in subsurface halite for up to 34,000 years. Five enrichment
      cultures, representing three genera of halophilic Archaea (Halorubrum,
      Natronomonas and Haloterrigena), were obtained from five surface-sterilized
      halite crystals exclusively in one section of the core (13.0-17.8 m; 22,000
      34,000 years old) containing perennial saline lake deposits. Prokaryote cells
      were observed microscopically in situ within fluid inclusions from every layer
      that produced culturable cells. Another 876 crystals analysed from depths of 8.1
      86.7 m (10,000-100,000 years old) failed to yield live halophilic Archaea.
      Considering the number of halite crystals tested (culturing success of 0.6%),
      microbial survival in fluid inclusions in halite is rare and related to the
      paleoenvironment, which controls the distribution and abundance of trapped
      microorganisms. Two cultures from two crystals at 17.8 m that yielded identical
      16S rRNA sequences (genus: Haloterrigena) demonstrate intra-laboratory
      reproducibility. Inter-laboratory reproducibility is shown by two halophilic
      Archaea (genus: Natronomonas), with 99.3% similarity of 16S rRNA sequences,
      cultured from the same core interval, but at separate laboratories.

PMID- 19840102
TI  - Limits of life in hostile environments: no barriers to biosphere function?
AB  - Environments that are hostile to life are characterized by reduced microbial
      activity which results in poor soil- and plant-health, low biomass and
      biodiversity, and feeble ecosystem development. Whereas the functional biosphere
      may primarily be constrained by water activity (a(w)) the mechanism(s) by which
      this occurs have not been fully elucidated. Remarkably we found that, for diverse
      species of xerophilic fungi at a(w) values of <or= 0.72, water activity per se
      did not limit cellular function. We provide evidence that chaotropic activity
      determined their biotic window, and obtained mycelial growth at water activities
      as low as 0.647 (below that recorded for any microbial species) by addition of
      compounds that reduced the net chaotropicity. Unexpectedly we found that some
      fungi grew optimally under chaotropic conditions, providing evidence for a
      previously uncharacterized class of extremophilic microbes. Further studies to
      elucidate the way in which solute activities interact to determine the limits of
      life may lead to enhanced biotechnological processes, and increased productivity
      of agricultural and natural ecosystems in arid and semiarid regions.

PMID- 19840100
TI  - The genome and structural proteome of an ocean siphovirus: a new window into the
      cyanobacterial 'mobilome'.
AB  - Prochlorococcus, an abundant phototroph in the oceans, are infected by members of
      three families of viruses: myo-, podo- and siphoviruses. Genomes of myo- and
      podoviruses isolated on Prochlorococcus contain DNA replication machinery and
      virion structural genes homologous to those from coliphages T4 and T7
      respectively. They also contain a suite of genes of cyanobacterial origin, most
      notably photosynthesis genes, which are expressed during infection and appear
      integral to the evolutionary trajectory of both host and phage. Here we present
      the first genome of a cyanobacterial siphovirus, P-SS2, which was isolated from
      Atlantic slope waters using a Prochlorococcus host (MIT9313). The P-SS2 genome is
      larger than, and considerably divergent from, previously sequenced siphoviruses.
      It appears most closely related to lambdoid siphoviruses, with which it shares 13
      functional homologues. The approximately 108 kb P-SS2 genome encodes 131
      predicted proteins and notably lacks photosynthesis genes which have consistently
      been found in other marine cyanophage, but does contain 14 other cyanobacterial
      homologues. While only six structural proteins were identified from the genome
      sequence, 35 proteins were detected experimentally; these mapped onto capsid and
      tail structural modules in the genome. P-SS2 is potentially capable of
      integration into its host as inferred from bioinformatically identified genetic
      machinery int, bet, exo and a 53 bp attachment site. The host attachment site
      appears to be a genomic island that is tied to insertion sequence (IS) activity
      that could facilitate mobility of a gene involved in the nitrogen-stress
      response. The homologous region and a secondary IS-element hot-spot in
      Synechococcus RS9917 are further evidence of IS-mediated genome evolution
      coincident with a probable relic prophage integration event. This siphovirus
      genome provides a glimpse into the biology of a deep-photic zone phage as well as
      the ocean cyanobacterial prophage and IS element 'mobilome'.

PMID- 19840103
TI  - Diel rhythm of nitrogen and carbon metabolism in the unicellular, diazotrophic
      cyanobacterium Crocosphaera watsonii WH8501.
AB  - We examined the diel variation in nitrogen and carbon metabolism in Crocosphaera
      watsonii WH8501 at the physiological and gene expression level in order to
      determine the temporal constraints for N2 fixation and photosynthesis. N2
      fixation and photosynthesis were restricted to the dark and light periods,
      respectively, during a 24 h light-dark cycle. All genes studied here except one
      (psbA2) showed diel variations in their expression levels. The highest variation
      was seen in nifH and nifX relative transcript abundance with a factor of 3
      5x10(3) between light and dark periods. Photosynthesis genes showed less
      variation with a maximum factor of about 500 and always had high relative
      transcript abundances relative to other genes. At the protein level, the
      photosystems appeared more stable than the nitrogenase complex over a 24 h light
      dark cycle, suggesting that C. watsonii retains the ability to photosynthesize
      during the dark period of the diel cycle. In contrast, nitrogenase is synthesized
      daily and exhibits peak abundance during the dark period. Our results have
      implications for field studies with respect to the interpretation of
      environmental gene expression data.

PMID- 19840104
TI  - Functional characterization of an anaerobic benzene-degrading enrichment culture
      by DNA stable isotope probing.
AB  - The flow of carbon under sulfate-reducing conditions within a benzene
      mineralizing enrichment culture was analysed using fully labelled [13C6]-benzene.
      Over 180 days of incubation, 95% of added 13C-benzene was released as 13C-carbon
      dioxide. DNA extracted from cultures that had degraded different amounts of
      unlabelled or 13C-labelled benzene was centrifuged in CsCl density gradients to
      identify 13C-benzene-assimilating organisms by density-resolved terminal
      restriction fragment length polymorphism analysis and cloning of 16S rRNA gene
      fragments. Two phylotypes showed significantly increased relative abundance of
      their terminal restriction fragments in 'heavy' fractions of 13C-benzene
      incubated microcosms compared with a 12C-benzene-incubated control: a member of
      the Cryptanaerobacter/Pelotomaculum group within the Peptococcaceae, and a
      phylotype belonging to the Epsilonproteobacteria. The
      Cryptanaerobacter/Pelotomaculum phylotype was the most frequent sequence type. A
      small amount of 13C-methane was aceticlastically produced, as concluded from the
      linear relationship between methane production and benzene degradation and the
      detection of Methanosaetaceae as the only methanogens present. Other phylotypes
      detected but not 13C-labelled belong to several genera of sulfate-reducing
      bacteria, that may act as hydrogen scavengers for benzene oxidation. Our results
      strongly support the hypothesis that benzene is mineralized by a consortium
      consisting of syntrophs, hydrogenotrophic sulfate reducers and to a minor extent
      of aceticlastic methanogens.

PMID- 19840105
TI  - NifA is required for maximal expression of denitrification genes in
      Bradyrhizobium japonicum.
AB  - In Bradyrhizobium japonicum the napEDABC, nirK, norCBQD and nosRZDYFLX genes,
      which encode reductases for nitrate, nitrite, nitric oxide and nitrous oxide,
      respectively, are required for denitrification. Microaerobic induction of these
      genes depends on fixLJ and fixK2, whose products form the FixLJ-FixK2 regulatory
      cascade. In B. japonicum, a second oxygen-responsive regulatory cascade mediated
      by the nitrogen fixation regulatory protein, NifA, has been described. In this
      study, we show that disruption of nifA caused a growth defect in B. japonicum
      cells, when grown under denitrifying conditions, and decreased activity of
      periplasmic nitrate and nitrite reductase enzymes was also observed. Furthermore,
      expression of napE-lacZ, nirK-lacZ or norC-lacZ transcriptional fusions, as well
      as levels of nirK transcripts were significantly reduced in the nifA mutant after
      incubation under nitrate-respiring conditions. Haem c staining analyses revealed
      that NifA is required for full synthesis of the NapC and NorC proteins, which are
      required for denitrification. A B. japonicum rpoN1/2 mutant, lacking both copies
      of the gene encoding the alternative sigma factor sigma54, was able to grow
      anaerobically with nitrate as terminal electron acceptor and showed wild-type
      levels of nitrate and nitrite reductase activities. We propose that the nitrogen
      fixation regulatory protein, NifA, is involved in the maximal expression of the
      denitrification genes in B. japonicum. This influence is independent of sigma54.

PMID- 19840108
TI  - Thomas' hematopoietic cell transplantation.

PMID- 19840107
TI  - Rock weathering creates oases of life in a high Arctic desert.
AB  - During primary colonization of rock substrates by plants, mineral weathering is
      strongly accelerated under plant roots, but little is known on how it affects
      soil ecosystem development before plant establishment. Here we show that rock
      mineral weathering mediated by chemolithoautotrophic bacteria is associated to
      plant community formation in sites recently released by permanent glacier ice
      cover in the Midtre Lovenbreen glacier moraine (78 degrees 53'N), Svalbard.
      Increased soil fertility fosters growth of prokaryotes and plants at the boundary
      between sites of intense bacterial mediated chemolithotrophic iron-sulfur
      oxidation and pH decrease, and the common moraine substrate where carbon and
      nitrogen are fixed by cyanobacteria. Microbial iron oxidizing activity determines
      acidity and corresponding fertility gradients, where water retention, cation
      exchange capacity and nutrient availability are increased. This fertilization is
      enabled by abundant mineral nutrients and reduced forms of iron and sulfur in
      pyrite minerals within a conglomerate type of moraine rock. Such an interaction
      between microorganisms and moraine minerals determines a peculiar, not yet
      described model for soil genesis and plant ecosystem formation with potential
      past and present analogues in other harsh environments with similar geochemical
      settings.

PMID- 19840106
TI  - Diversity and population structure of sewage-derived microorganisms in wastewater
      treatment plant influent.
AB  - The release of untreated sewage introduces non-indigenous microbial populations
      of uncertain composition into surface waters. We used massively parallel 454
      pyrosequencing of hypervariable regions in rRNA genes to profile microbial
      communities from eight untreated sewage influent samples of two wastewater
      treatment plants (WWTPs) in metropolitan Milwaukee. The sewage profiles included
      a discernible human faecal signature made up of several taxonomic groups
      including multiple Bifidobacteriaceae, Coriobacteriaceae, Bacteroidaceae,
      Lachnospiraceae and Ruminococcaceae genera. The faecal signature made up a small
      fraction of the taxa present in sewage but the relative abundance of these
      sequence tags mirrored the population structures of human faecal samples. These
      genera were much more prevalent in the sewage influent than standard indicators
      species. High-abundance sequences from taxonomic groups within the Beta- and
      Gammaproteobacteria dominated the sewage samples but occurred at very low levels
      in faecal and surface water samples, suggesting that these organisms proliferate
      within the sewer system. Samples from Jones Island (JI--servicing residential
      plus a combined sewer system) and South Shore (SS--servicing a residential area)
      WWTPs had very consistent community profiles, with greater similarity between
      WWTPs on a given collection day than the same plant collected on different days.
      Rainfall increased influent flows at SS and JI WWTPs, and this corresponded to
      greater diversity in the community at both plants. Overall, the sewer system
      appears to be a defined environment with both infiltration of rainwater and
      stormwater inputs modulating community composition. Microbial sewage communities
      represent a combination of inputs from human faecal microbes and enrichment of
      specific microbes from the environment to form a unique population structure.

PMID- 19840109
TI  - A critical role for dynamic changes in histone H3 methylation at the Bdnf
      promoter during postnatal thermotolerance acquisition.
AB  - As with other sensory mechanisms, determination of the thermal-control set point
      is refined during a critical period of development by alterations in cellular
      properties in the frontal hypothalamus. These alterations in hypothalamic
      plasticity are achieved by renewal of the protein repertoire via activation or
      silencing of gene transcription, both of which are regulated by histone
      modifications. This study demonstrates induction of global histone H3 lysine 27
      (H3K27) dimethylation, with no changes in its trimethylation levels, in the
      frontal hypothalamus, as well as at the promoter of the brain-derived
      neurotrophic factor (BDNF) gene during thermal-control establishment.
      Furthermore, antisense 'knockdown' of the H3K27-specific methyltransferase,
      enhancer of zeste 2, which was induced in correlation with the dimethylation of
      H3K27, inhibited Bdnf mRNA expression and disrupted the establishment of
      thermoregulation. This phenotypic effect was partially rescued by intracranial
      injection of BDNF. The presented findings highlight the specific epigenetic role
      of chromatin modifications in thermal-control establishment.

PMID- 19840111
TI  - Two crossed axonal projections contribute to binaural unmasking of frequency
      following responses in rat inferior colliculus.
AB  - Frequency-following responses (FFRs) are sustained potentials based on phase
      locked neural activities elicited by low- to medium-frequency periodical sound
      waveforms. Human brainstem FFRs, which are able to encode some critical acoustic
      features of speech, can be unmasked by binaural processing. However, the
      underlying unmasking mechanisms have not previously been reported. In rats, most
      neurons in the inferior colliculus (IC) exhibit binaural responses which are
      affected by axonal projections from both the contralateral dorsal nucleus of the
      lateral lemniscus (DNLL) and the contralateral IC. The present study investigated
      whether the contralateral DNLL and the contralateral IC modulate binaural
      unmasking of FFRs recorded in the rat IC. The results show that IC FFRs to the
      rat pain call (chatter) were enhanced by local injection of the excitatory
      glutamate receptor antagonist kynurenic acid (KYNA) into the contralateral DNLL
      but were reduced by KYNA injection into the contralateral IC. Introducing a
      disparity between the interaural time difference (ITD) of the FFR-eliciting
      chatter and the ITD of the masking noise enhanced IC FFRs. Moreover, the ITD
      disparity-induced FFR enhancement was weakened by injection of KYNA into either
      the contralateral DNLL or the contralateral IC when the ipsilateral chatter
      preceded the contralateral chatter. Thus, binaural hearing can improve IC FFRs
      against noise masking. More importantly, both inhibitory projections from the
      contralateral DNLL and excitatory projections from the contralateral IC modulate
      IC FFRs and play a role in forming binaural unmasking of IC FFRs.

PMID- 19840110
TI  - Population coding of tone stimuli in auditory cortex: dynamic rate vector
      analysis.
AB  - Neural representations of even temporally unstructured stimuli can show complex
      temporal dynamics. In many systems, neuronal population codes show 'progressive
      differentiation', whereby population responses to different stimuli grow further
      apart during a stimulus presentation. Here we analysed the response of auditory
      cortical populations in rats to extended tones. At onset (up to 300 ms), tone
      responses involved strong excitation of a large number of neurons; during
      sustained responses (after 500 ms) overall firing rate decreased, but most cells
      still showed statistically significant rate modulation. Population vector
      trajectories evoked by different tone frequencies expanded rapidly along an
      initially similar trajectory in the first tens of milliseconds after tone onset,
      later diverging to smaller amplitude fixed points corresponding to sustained
      responses. The angular difference between onset and sustained responses to the
      same tone was greater than between different tones in the same stimulus epoch. No
      clear orthogonalization of responses was found with time, and predictability of
      the stimulus from population activity also decreased during this period compared
      with onset. The question of whether population activity grew more or less sparse
      with time depended on the precise mathematical sense given to this term. We
      conclude that auditory cortical population responses to tones differ from those
      reported in many other systems, with progressive differentiation not seen for
      sustained stimuli. Sustained acoustic stimuli are typically not behaviorally
      salient: we hypothesize that the dynamics we observe may instead allow an animal
      to maintain a representation of such sounds, at low energetic cost.

PMID- 19840112
TI  - Influence of photoperiod duration and light-dark transitions on entrainment of
      Per1 and Per2 gene and protein expression in subdivisions of the mouse
      suprachiasmatic nucleus.
AB  - The circadian clock located within the suprachiasmatic nuclei (SCN) of the
      hypothalamus responds to changes in the duration of day length, i.e. photoperiod.
      Recently, changes in phase relationships among the SCN cell subpopulations,
      especially between the rostral and caudal region, were implicated in the SCN
      photoperiodic modulation. To date, the effect of abrupt, rectangular, light-to
      dark transitions have been studied while in nature organisms experience gradual
      dawn and twilight transitions. The aim of this study was to compare the effect of
      a long (18 h of light) and a short (6 h of light) photoperiod with twilight
      relative to that with rectangular light-to-dark transition on the daily profiles
      of Per1 and Per2 mRNA (in situ hybridization) and PER1 and PER2 protein
      (immunohistochemistry) levels within the rostral, middle and caudal regions of
      the mouse SCN. Under the short but not under the long photoperiod, Per1, Per2 and
      PER1, PER2 profiles were significantly phase-advanced under the twilight relative
      to rectangular light-to-dark transition in all SCN regions examined. Under the
      photoperiods with rectangular light-to-dark transition, Per1 and Per2 mRNA
      profiles in the caudal SCN were phase-advanced as compared with those in the
      rostral SCN. The phase differences between the SCN regions were reduced under the
      long, or completely abolished under the short, photoperiods with twilight. The
      data indicate that the twilight photoperiod provides stronger synchronization
      among the individual SCN cell subpopulations than the rectangular one, and the
      effect is more pronounced under the short than under the long photoperiod.

PMID- 19840113
TI  - Analysis of the nicastrin promoter rs10752637 polymorphism and its association
      with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a common, degenerative form of dementia characterized
      by the accumulation of plaques containing amyloid beta-peptides (A beta).
      Nicastrin (NCSTN) is a type I trans-membrane glycoprotein and an essential
      component of gamma-secretase, a multiprotein complex required for the production
      of the mature form of A beta. Overexpression of wild-type NCSTN increases A beta
      production, indicating that the strict regulation of NCSTN expression may play a
      fundamental role in the pathogenesis of AD. In this study we investigated the
      effect of a single-nucleotide polymorphism (SNP; rs10752637), located in the
      promoter region of the NCSTN gene, on NCSTN promoter activity. First, the
      rs10752637 genotypes were determined in a Chinese population consisting of 462
      patients with sporadic AD and 470 normal control subjects. The distributions of
      the rs10752637 genotypes and allele frequencies were significantly different
      between the AD and control groups, with the -922T allele significantly associated
      with the occurrence of AD. Reporter assays indicated that the rs10752637 -922T
      allele had a significantly increased promoter activity relative to the -922G
      allele. Furthermore, gel shift assays demonstrated that the -922T allele
      preferentially bound to components of nuclear extracts. Overall, our results
      indicate that the rs10752637 SNP can likely influence the expression of NCSTN,
      and that this may be an influencing factor during the pathogenesis of AD.

PMID- 19840114
TI  - The role of a groundwater bacterial community in the degradation of the herbicide
      terbuthylazine.
AB  - A bacterial community in an aquifer contaminated by s-triazines was studied.
      Groundwater microcosms were treated with terbuthylazine at a concentration of 100
      microg L(-1) and degradation of the herbicide was assessed. The bacterial
      community structure (abundance and phylogenetic composition) and function (carbon
      production and cell viability) were analysed. The bacterial community was able to
      degrade the terbuthylazine; in particular, Betaproteobacteria were involved in
      the herbicide biotransformation. Identification of some bacterial isolates by PCR
      amplification of the 16S rRNA gene revealed the presence of two
      Betaproteobacteria species able to degrade the herbicide: Advenella incenata and
      Janthinobacterium lividum. PCR detection of the genes encoding s-triazine
      degrading enzymes indicated the presence of the atzA and atzB genes in A.
      incenata and the atzB and atzC genes in J. lividum. The nucleotide sequences of
      the PCR fragments of the atz genes from these strains were 100% identical to the
      homologous genes of the Pseudomonas sp. strain ADP. In conclusion, the results
      show the potential for the use of a natural attenuation strategy in the treatment
      of aquifers polluted with the terbuthylazine. The two bacteria isolated could
      facilitate the implementation of effective bioremediation protocols, especially
      in the case of the significant amounts of herbicide that can be found in
      groundwater as a result of accidental spills.

PMID- 19840115
TI  - Regulation of endo-polygalacturonase activity in Saccharomyces cerevisiae.
AB  - Pectolytic activity in Saccharomyces cerevisiae is due to the secretion of an
      endo-polygalacturonase encoded by the PGU1 gene. The ability to degrade
      polygalacturonic acid has been shown to vary between different strains. In this
      study, we attempted to elucidate how pectolytic activity is regulated in S.
      cerevisiae and to determine whether the means of regulation differ between
      strains. Saccharomyces cerevisiae strains from different genetic backgrounds,
      with varying ability to degrade pectin, were compared. Activity was found not to
      be regulated by sequence differences in the PGU1 gene, but by the transcription
      level of the gene. Expression of PGU1 was found to be determined by the
      transcription level of its two transcription factors TEC1 and STE12. The
      activation of PGU1 transcription by galactose was found to be strain specific,
      independent of the strain being an industrial or a domesticated one. The
      EUROSCARF yeast deletion library was screened for genes encoding inhibitors and
      activators of polygalacturonase activity. Fourteen strains were identified, in
      which deletion of a specific gene resulted in a recovery of polygalacturonase
      activity; these genes were identified as encoding inhibitors of polygalacturonase
      activity, and two activators were identified.

PMID- 19840116
TI  - Generation of a large set of genetically tractable haploid and diploid
      Saccharomyces strains.
AB  - Saccharomyces cerevisiae has proved to be an invaluable model in classical and
      molecular genetics studies. Despite several hundreds of isolates already
      available, the scientific community relies on the use of only a handful of
      unrelated strains. The lack of sequence information, haploid derivatives and
      genetic markers has prevented novel strains from being used. Here, we release a
      set of 55 S. cerevisiae and Saccharomyces paradoxus genetically tractable
      strains, previously sequenced in the Saccharomyces Genome Resequencing Project.
      These strains are stable haploid derivatives and ura3 auxotrophs tagged with a 6
      bp barcode, recognized by a restriction enzyme to allow easy identification. We
      show that the specific barcode can be used to accurately measure the prevalence
      of different strains during competition experiments. These strains are now
      amenable to a wide variety of genetic experiments and can be easily crossed with
      each other to create hybrids and segregants, providing a valuable resource for
      breeding programmes and quantitative genetic studies. Three versions of each
      strain (haploid Mat a and Mat alpha and diploid Mat a/alpha all as ura3::KanMX
      Barcode) are available through the National Culture Yeast Collection.

PMID- 19840117
TI  - Spathaspora arborariae sp. nov., a d-xylose-fermenting yeast species isolated
      from rotting wood in Brazil.
AB  - Four strains of a new yeast species were isolated from rotting wood from two
      sites in an Atlantic Rain Forest and a Cerrado ecosystem in Brazil. The analysis
      of the sequences of the D1/D2 domains of the large-subunit rRNA gene showed that
      this species belongs to the Spathaspora clade. The new species ferments D-xylose
      efficiently and is related to Candida jeffriesii and Spathaspora passalidarum,
      both of which also ferment D-xylose. Similar to S. passalidarum, the new species
      produces unconjugated asci with a single greatly elongated ascospore with curved
      ends. The type strain of Spathaspora arborariae sp. nov. is UFMG-HM19.1A(T)
      (=CBS11463(T)=NRRL Y-48658(T)).

PMID- 19840118
TI  - Optimized fermentation of grape juice by laboratory strains of Saccharomyces
      cerevisiae.
AB  - Laboratory strains of yeast (Saccharomyces cerevisiae) based on S288C ferment
      grape juice relatively poorly. We show that slow fermentation appears to be
      inherent to this strain, because the original S288C isolate shows fermentation
      similar to current laboratory isolates. We demonstrate further that some
      auxotrophic mutations in the laboratory strain show reduced rates of fermentation
      in grape juice, with lysine auxotrophs particularly impaired compared with
      isogenic Lys(+) strains. Supplementing lysine at a 10-fold higher concentration
      than recommended allowed yeast cultures to reach higher final cell densities and
      restored the fermentation rate of auxotrophic strains to those of the
      corresponding wild-type strains. However, even with the additional
      supplementation, the fermentation rates of S288C strains were still slower than
      those of a commercial wine yeast strain. Conditions were developed that enable
      auxotrophic laboratory strains derived from S288C to ferment grape juice to
      completion with high efficiency on a laboratory scale. Fermentation in media
      based on grape juice will allow the suite of molecular genetic tools developed
      for these laboratory strains to be used in investigations of complex ferment
      characteristics and products.

PMID- 19840119
TI  - Recovery of endo-polygalacturonase activity in wine yeast and its effect on wine
      aroma.
AB  - The PGU1 gene, which encodes an endo-polygalacturonase, is present in most
      strains of Saccharomyces cerevisiae. In some strains that lack activity, the PGU1
      gene was replaced by a partial transposon. In an attempt to restore enzyme
      activity, the PGU1 gene was successfully reintroduced into its native position in
      five of these strains. Polygalacturonase activity was recovered in strains UCLMS
      1, -3 and -4, while Collection Cepage Cabernet and L2226 did not show any
      transcription of the gene after integration. Small-scale fermentations, under
      conditions mimicking those of winemaking, were carried out with the recombinant
      strains to determine the effect of an endo-polygalacturonase-producing wine
      strain on the wine aroma. Some statistically significant tendencies were observed
      for the production of certain compounds whose concentrations were higher in the
      wine made from the recombinant strains than that from their respective wild
      types. These differences might therefore induce a slight change in the aroma
      profile of the wines. Moreover, recovery of endo-polygalacturonase activity in
      certain wine strains did, however, provide an insight into the regulation of PGU1
      in these strains.

PMID- 19840121
TI  - Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2
      reveals a new role for BACE2.
AB  - BACE2 is homologous to BACE1, a beta-secretase that is involved in the
      amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down
      syndrome critical region of chromosome 21. Alzheimer disease neuropathology is
      common in Down syndrome patients at relatively early ages, and it has thus been
      speculated that BACE2 co-overexpression with APP would promote the early
      neurodegenerative phenotype. However, the in vivo function of BACE2 has not yet
      been elucidated. The aim of the present work has been to analyse the impact of in
      vivo BACE2 overexpression using a transgenic mouse model. Our results suggest
      that BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or
      cholinergic degeneration. However, TgBACE2 animals showed increased anxiety-like
      behaviour along with increased numbers of noradrenergic neurones in locus
      coeruleus, thus suggesting an unexpected role of BACE2 overexpression.

PMID- 19840120
TI  - Drug reimbursement and GPs' prescribing decisions: a randomized case-vignette
      study about the pharmacotherapy of obesity associated with type 2 diabetes: how
      GPs react to drug reimbursement.
AB  - This study sought to identify the effect of drug reimbursability--a decision made
      in France by the National Authority for Health--on physicians' prescribing
      practices for a diet drug such as rimonabant, approved for obese or overweight
      patients with type-2 diabetes. A cross-sectional survey of French general
      practitioners (GPs) presented a case-vignette about a patient for whom this drug
      is indicated in two alternative versions, differing only in its reimbursability,
      to two separate randomized subsamples of GPs in early 2007, before any decision
      was made about reimbursement. The results indicate that (i) more than 20% of GPs
      in private practice would be willing to prescribe a non-reimbursed diet drug for
      patients with obesity complicated by type 2 diabetes; (ii) the number of GPs
      willing to prescribe it would increase by 47.6% if the drug were reimbursed, and
      (iii) such a drug would be adopted at a higher rate by GPs who have regular
      contacts with pharmaceutical sales representatives. In France, unlike most other
      countries, drug reimbursement status is a signal of quality. However, our results
      suggest that a significant proportion of GPs would spontaneously adopt anti
      obesity drugs even if they were not reimbursed. Decisions about reimbursement of
      pharmaceutical products should be made taking into account that reimbursement is
      likely to intensify prescription.

PMID- 19840122
TI  - Comparative analysis of changes in gene expression due to RNA melting activities
      of translation initiation factor IF1 and a cold shock protein of the CspA family.
AB  - In Escherichia coli, temperature downshift elicits cold shock response, which is
      characterized by induction of cold shock proteins. CspA, the major cold shock
      protein of E. coli, helps cells to acclimatize to low temperature by melting the
      secondary structures in nucleic acids and acting as a transcription
      antiterminator. CspA and its homologues contain the cold shock domain and belong
      to the oligomer binding protein family, which also includes S1 domain proteins
      such as IF1. Structural similarity between IF1 and CspA homologues suggested a
      functional overlap between these proteins. Indeed IF1 can melt secondary
      structures in RNA and acts as transcription antiterminator in vivo and in vitro.
      Here, we show that in spite of having these critical activities, IF1 does not
      complement cold-sensitivity of a csp quadruple deletion strain. DNA microarray
      analysis shows that overproduction of IF1 and Csp leads to changes in expression
      of different sets of genes. Importantly, several genes which were previously
      shown to require Csp proteins for their expression at low temperature did not
      respond to IF1. Moreover, in vitro, we show that a transcription terminator
      responsive to Csp does not respond to IF1. Our results suggest that Csp proteins
      and IF1 have different sets of target genes as they may be suppressing the
      function of different types of transcription termination elements in specific
      genes.

PMID- 19840123
TI  - The water table.

PMID- 19840124
TI  - Improved resolution of ambient flow through fractured rock with temperature logs.
AB  - In contaminant hydrogeology, investigations at fractured rock sites are typically
      undertaken to improve understanding of the fracture networks and associated
      groundwater flow that govern past and/or future contaminant transport.
      Conventional hydrogeologic, geophysical, and hydrophysical techniques used to
      develop a conceptual model are often implemented in open boreholes under
      conditions of cross-connected flow. A new approach using high-resolution
      temperature (+/-0.001 degrees C) profiles measured within static water columns of
      boreholes sealed using continuous, water-inflated, flexible liners (FLUTe)
      identifies hydraulically active fractures under ambient (natural) groundwater
      flow conditions. The value of this approach is assessed by comparisons of
      temperature profiles from holes (100 to 200 m deep) with and without liners at
      four contaminated sites with distinctly different hydrogeologic conditions. The
      results from the lined holes consistently show many more hydraulically active
      fractures than the open-hole profiles, in which the influence of vertical flow
      through the borehole between a few fractures masks important intermediary flow
      zones. Temperature measurements in temporarily sealed boreholes not only improve
      the sensitivity and accuracy of identifying hydraulically active fractures under
      ambient conditions but also offer new insights regarding previously unresolvable
      flow distributions in fractured rock systems, while leaving the borehole
      available for other forms of testing and monitoring device installation.

PMID- 19840125
TI  - Arsenic geochemistry and hydrostratigraphy in midwestern U.S. glacial deposits.
AB  - Arsenic concentrations exceeding the U.S. EPA's 10 MUg/L standard are common in
      glacial aquifers in the midwestern United States. Previous studies have indicated
      that arsenic occurs naturally in these aquifers in association with metal
      (hydr)oxides and is released to groundwater under reducing conditions generated
      by microbial oxidation of organic matter. Despite this delineation of the arsenic
      source and mechanism of arsenic mobilization, identification of arsenic-impacted
      aquifers is hindered by the heterogeneous and discontinuous nature of glacial
      sediments. In much of the Midwest, the hydrostratigraphy of glacial deposits is
      not sufficiently characterized to predict where elevated arsenic concentrations
      are likely to occur. This case study from southeast Wisconsin presents a detailed
      characterization of local stratigraphy, hydrostratigraphy, and geochemistry of
      the Pleistocene glacial deposits and underlying Silurian dolomite. Analyses of a
      single core, water chemistry data, and well construction reports enabled
      identification of two aquifers separated by an organic-rich aquitard. The upper,
      unconfined aquifer provides potable water, whereas arsenic generally exceeds 10
      MUg/L in the deeper aquifer. Although coring and detailed hydrostratigraphic
      characterization are often considered impractical, our results demonstrate that a
      single core improved interpretation of the complex lithology and
      hydrostratigraphy. This detailed characterization of hydrostratigraphy
      facilitated development of well construction guidelines and lays the ground work
      for further studies of the complex interactions among aquifer sediments,
      hydrogeology, water chemistry, and microbiology that lead to elevated arsenic in
      groundwater.

PMID- 19840126
TI  - A Black Hills-Madison Aquifer origin for Dakota Aquifer groundwater in
      northeastern Nebraska.
AB  - Previous studies of the Dakota Aquifer in South Dakota attributed elevated
      groundwater sulfate concentrations to Madison Aquifer recharge in the Black Hills
      with subsequent chemical evolution prior to upward migration into the Dakota
      Aquifer. This study examines the plausibility of a Madison Aquifer origin for
      groundwater in northeastern Nebraska. Dakota Aquifer water samples were collected
      for major ion chemistry and isotopic analysis ((18)O, (2)H, (3)H, (14)C, (13)C,
      (34)S, (18)O-SO(4), (87)Sr, (37)Cl). Results show that groundwater beneath the
      eastern, unconfined portion of the study area is distinctly different from
      groundwater sampled beneath the western, confined portion. In the east,
      groundwater is calcium-bicarbonate type, with delta(18)O values (-9.6 per
      thousand to -12.4 per thousand) similar to local, modern precipitation (-7.4 per
      thousand to -10 per thousand), and tritium values reflecting modern recharge. In
      the west, groundwater is calcium-sulfate type, having depleted delta(18)O values
      (-16 per thousand to -18 per thousand) relative to local, modern precipitation,
      and (14)C ages 32,000 to more than 47,000 years before present. Sulfate,
      delta(18)O, delta(2)H, delta(34)S, and delta(18)O-SO(4) concentrations are
      similar to those found in Madison Aquifer groundwater in South Dakota. Thus, it
      is proposed that Madison Aquifer source water is also present within the Dakota
      Aquifer beneath northeastern Nebraska. A simple Darcy equation estimate of
      groundwater velocities and travel times using reported physical parameters from
      the Madison and Dakota Aquifers suggests such a migration is plausible. However,
      discrepancies between (14)C and Darcy age estimates indicate that (14)C ages may
      not accurately reflect aquifer residence time, due to mixtures of varying aged
      water.

PMID- 19840128
TI  - Quality of private personal care for elderly people in Italy living at home with
      disabilities: risk of nursing home placement at a 1-year follow-up.
AB  - The aim of this prospective study was to evaluate the correlation between the
      self-perceived quality of private personal care for elderly people living at home
      and the 1-year risk of hospital admission, nursing home placement and death. We
      enrolled 100 community-dwelling elderly outpatients (mean age 85 years), who had
      been receiving private personal care for any kind of disability for at least 1
      month. Quality of care was described by both the elderly person without overt
      cognitive impairment and their informal caregivers, and this was categorised for
      analysis as 'poor or fair' or 'optimal or intermediate'. Rates of hospital
      admission, long-term care placement and death were assessed at a 1-year follow
      up, between May 2006 and January 2008. One year after enrollment, 67 elderly
      people were still living at home, 10 had been institutionalised and 23 had died.
      Forty-six had experienced at least one hospital admission. The elderly people
      belonging to the 'poor or fair care' group (n = 16) showed a higher risk of
      nursing home placement when compared to the people belonging to the 'optimal or
      intermediate care' group (n = 84) (relative risk = 5.25, 95% confidence interval
      1.72-16.06), without there being any significant difference between the two
      groups in terms of baseline assessment and basic functional status at follow-up.
      The quality of personal care was not a predictor of either hospital admission or
      death. Therefore, a poor or fair quality of personal care turned out to be a 1
      year predictor of placement in a long-term care facility for community-dwelling
      older adults with a disability.

PMID- 19840129
TI  - Telling stories from everyday practice, an opportunity to see a bigger picture: a
      participatory action research project about developing discharge planning.
AB  - In spite of laws, rules and routines, findings from Swedish as well as
      international research show that discharge planning is not a simple matter. There
      is considerable knowledge about discharge planning, but the quality of the actual
      process in practice remains poor. With this in mind, a research and developmental
      health and social care network decided to use participation action research to
      explore the discharge planning situation in order to generate new ideas for
      development. This paper reports on the research process and the findings about
      our enhanced understanding about the discharge planning situation. Story dialogue
      method was used. The method is based on stories from everyday practice. The
      stories are used as 'triggers' to ask probing questions in a dialog and
      structured form. Local theory is developed to help the participants to find
      solutions for action in the practice. Our findings were that the discharge
      planning situation could be seen as a system including three interconnected
      areas: patient participation, practitioners' competence and organizational
      support. To reach good quality in discharge planning, all these three issues need
      to be developed, but not only as routines and forms. Rather, when developing a
      discharge planning situation, a system where relational aspects such as
      confidence and continuity are essential and thus needs to be considered. To
      achieve a change, the core problem needs to be clarified. When the issue is
      complex, the solution needs to consider the bigger picture and not just the
      parts. Telling stories from everyday practice, and to systematically reflect and
      analyse those in interprofessional groups can create opportunities for enhanced
      understanding, as well as be a vehicle for future change of practice.

PMID- 19840131
TI  - What, if anything, is specific about having a rare disorder? Patients' judgements
      on being ill and being rare.
AB  - BACKGROUND: Growing efforts are made to improve the situation of persons with
      rare diseases, but the specific nature of these disorders remains unclear.
      OBJECTIVES: To establish (1) to what extent people with rare disorders think that
      their disease's rarity causes particular difficulties, (2) to what extent these
      difficulties relate to other causes than rarity (i.e. other characteristics of
      the disease or other components of the illness experience), (3) to what extent
      the rarity of the disease may relate to components of patients' experience other
      than those that are traditionally addressed (i.e. personal or daily life
      aspects). METHODS: Semi-structured interviews with 29 patients and 15 parents of
      children with one of six rare diseases (cystic fibrosis, fragile X syndrome,
      Wilson's disease, mastocytosis, locked-in syndrome and a sixth syndrome). The
      interviews were conducted in France. The analysis draws on French pragmatic
      sociology and focuses on the participants' judgements of their experience.
      Findings The participants considered as normal and acceptable a range of
      situations that are often viewed as specific to rare disorders and unfair. This
      rather positive evaluation was conditional on some specific moral criteria being
      met. The participants attributed the cause of their difficulties to the failure
      of health professionals to meet these criteria. In the participants' experience,
      disease-related associations play a key role and rarity seems to contribute to
      making them especially important. CONCLUSIONS: Patients' experience would be
      considerably improved if health professionals more often fulfilled their moral
      expectations, especially regarding diagnosis disclosure and information. (250
      words).

PMID- 19840132
TI  - Does major illness cause financial catastrophe?
AB  - OBJECTIVE: We examine the financial impact of major illnesses on the near-elderly
      and how this impact is affected by health insurance. DATA SOURCES: We use RAND
      Corporation extracts from the Health and Retirement Study from 1992 to 2006.(1)
      STUDY DESIGN: Our dependent variable is the change in household assets, excluding
      the value of the primary home. We use triple difference median regressions on a
      sample of newly ill/uninsured near elderly (under age 65) matched to newly
      ill/insured near elderly. We also include a matched control group of households
      whose members are not ill. RESULTS: Controlling for the effects of insurance
      status and illness, we find that the median household with a newly ill, uninsured
      individual suffers a statistically significant decline in household assets of
      between 30 and 50 percent relative to households with matched insured
      individuals. Newly ill, insured individuals do not experience a decline in
      wealth. CONCLUSIONS: Newly ill/uninsured households appear to be one illness away
      from financial catastrophe. Newly ill insured households who are matched to
      uninsured households appear to be protected against financial loss, at least in
      the near term.

PMID- 19840133
TI  - Show us the money: lessons in transparency from state pharmaceutical marketing
      disclosure laws.
AB  - OBJECTIVE: To assess legislation requiring drug companies to report gifts to
      providers, and to evaluate the information obtained. DATA SOURCES: Data included
      legislation in Vermont, Minnesota, Maine, Massachusetts, West Virginia, and the
      District of Columbia, and company disclosure data from Vermont. STUDY DESIGN: We
      evaluated the strengths and weaknesses of state legislation. We also analyzed 4
      years of company disclosures from Vermont, assessing the value and distribution
      of industry-provider exchanges and identifying emerging trends in companies'
      practices. DATA COLLECTION METHODS: State legislation is publically available. We
      obtained Vermont's data through requests to the state's Attorney General's
      office. PRINCIPAL FINDINGS: Of the state laws, only Vermont's yielded robust,
      publically available data. These data show gifting was dominated by a few major
      corporations, and <2 percent of Vermont's prescribers received 69 percent of
      gifts and payments. Companies were especially generous to specialists in
      psychiatry, endocrinology/diabetes/metabolism, internal medicine, and neurology.
      Companies increasingly used loopholes in the law to avoid public scrutiny.
      CONCLUSIONS: Disclosure laws are an important first step in bringing greater
      transparency to physician-industry relationships. But flaws and weaknesses limit
      the states' ability to render physician-industry exchanges fully transparent.
      Future efforts should build on these lessons to render physician-industry
      relationships fully transparent.

PMID- 19840134
TI  - Trends in hospital cost and revenue, 1994-2005: how are they related to HMO
      penetration, concentration, and for-profit ownership?
AB  - OBJECTIVE: Analyze trends in hospital cost and revenue, as well as price and
      quantity (1994-2005) as a function of health maintenance organization (HMO)
      penetration, HMO concentration, and for-profit (FP) HMO market share. DATA:
      Medicare hospital cost reports, AHA Annual Surveys, HMO data from Interstudy, and
      other supplemental data. STUDY DESIGN: A retrospective study of all short-term,
      general, nonfederal hospitals in metropolitan statistical areas (MSAs) in the
      United States from 1994 to 2005, using hospital/MSA fixed-effects translog
      regression models. PRINCIPAL FINDINGS: A 10 percentage point increase in HMO
      enrollment is associated with 4.1-4.2 percent reduction in costs and revenues in
      the pre-2000 period but only a 2.1-2.5 percent reduction in the post-2000 period.
      Hospital revenue in HMO-dominant markets (highly concentrated HMO market and
      competitive hospital market) is 19-27 percent lower than other types of markets,
      and the difference is most likely due mainly to lower prices and to a lesser
      extent lower utilization. CONCLUSIONS: The historical difference of lower
      spending in high HMO penetration markets compared with low HMO markets narrowed
      after 2000 and the relative concentration between HMO and hospital markets can
      substantially influence hospital spending. Additional research is needed to
      understand how different aspects of these two markets have changed and interacted
      and how they are causally linked to spending trends.

PMID- 19840135
TI  - SCHIP's impact on dependent coverage in the small-group health insurance market.
AB  - OBJECTIVE: To estimate the impact of State Children's Health Insurance Program
      (SCHIP) expansions on public and private coverage of dependents at small firms
      compared with large firms. DATA SOURCES: 1996-2007 Annual Demographic Survey of
      the Current Population Survey (CPS). STUDY DESIGN: This study estimates a two
      stage least squares (2SLS) model for four insurance outcomes that instruments for
      SCHIP and Medicaid eligibility. Separate models are estimated for small group
      markets (firms with fewer than 25 employees), small businesses (firms under 500
      employees), and large firms (firms 500 employees and above). DATA
      COLLECTION/EXTRACTION METHODS: We extracted data from the 1996-2007 CPS for
      children in households with at least one worker. PRINCIPAL FINDINGS: The SCHIP
      expansions decreased the percentage of uninsured dependents in the small group
      market by 7.6 percentage points with negligible crowd-out in the small group and
      no significant effect on private coverage across the 11-year-period. CONCLUSIONS:
      The SCHIP expansions have increased coverage for households in the small group
      market with no significant crowd-out of private coverage. In contrast, the
      estimates for large firms are consistent with the substantial crowd-out observed
      in the literature.

PMID- 19840136
TI  - The utility of the state buy-in variable in the Medicare denominator file to
      identify dually eligible Medicare-Medicaid beneficiaries: a validation study.
AB  - OBJECTIVE: To compare the adequacy of the state buy-in variable (SBI) in the
      Medicare denominator file to identify dually eligible patients. DATA SOURCE/STUDY
      SETTINGS: We used linked Medicare and Medicaid data from Michigan and Ohio for
      elders diagnosed with incident breast, prostate, or colorectal cancer between
      1996 and 2001. STUDY DESIGN: Using the Medicaid enrollment file as the "gold
      standard," we assessed the number of duals from Medicare files in cross-sectional
      and longitudinal analyses. DATA COLLECTION/EXTRACTION METHODS: Data for the study
      population were linked with Medicare and Medicaid files using patient
      identifiers. PRINCIPAL FINDINGS: Sensitivity was low (74.2 percent, 95 percent
      confidence interval [CI]: 72.7, 75.6 and 80.8 percent, 79.7, 81.9, in Michigan
      and Ohio, respectively). PPV was above 95 percent in Michigan and 88.8 percent in
      Ohio. Both sensitivity and PPV varied between and within the states. Both in
      Michigan and in Ohio, we observed limited agreement on the length of enrollment
      in Medicaid between the two data sources. CONCLUSIONS: Except to examine
      disparities by dual status at a very broad level, the SBI variable alone may be
      inadequate to identify duals. The findings call for improvements in Medicare and
      Medicaid information management systems and for uniformity in database linking
      strategies.

PMID- 19840137
TI  - Has pay-for-performance decreased access for minority patients?
AB  - OBJECTIVE: To examine whether the CMS and Premier Inc. Hospital Quality Incentive
      Demonstration (PHQID), a hospital-based pay-for-performance (P4P) and public
      quality reporting program, caused participating hospitals (1) to avoid treating
      minority patients diagnosed with acute myocardial infarction (AMI), heart
      failure, and pneumonia and (2) to avoid providing coronary artery bypass graft
      (CABG) to minority patients diagnosed with AMI. DATA SOURCES: One hundred percent
      Medicare inpatient claims, denominator files, and provider of service files from
      2000 to 2006. STUDY DESIGN: We test for differences in the conditional
      probability of receiving care at PHQID hospitals for AMI, heart failure, and
      pneumonia before and after implementation of the PHQID between white and minority
      patients. We also test for differences in the conditional probability that white
      and minority patients diagnosed with AMI receive CABG in hospitals participating,
      and not participating, in the PHQID before and after the implementation of the
      PHQID. DATA EXTRACTION METHODS: Data were obtained from CMS. PRINCIPAL FINDINGS:
      We find little evidence that the PHQID reduced access for minority patients: only
      "Other Race" beneficiaries had a significant reduction in adjusted admissions to
      PHQID hospitals in the postperiod, and only for AMI. Only marginally significant
      ( p<.10) evidence of a reduction in CABG was found, also occurring for Other Race
      beneficiaries. CONCLUSIONS: Despite minimal evidence of minority patient
      avoidance in the PHQID, monitoring of avoidance should continue for P4P programs.

PMID- 19840139
TI  - Encapsulating peritoneal sclerosis: importance to the hemodialysis practitioner.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication
      of long-term peritoneal dialysis (PD) therapy. Encapsulating peritoneal sclerosis
      is characterized by peritoneal membrane inflammation, followed by progressive
      peritoneal membrane fibrosis and intestinal encapsulation. Clinical
      manifestations include ascites as well as intermittent and recurrent small bowel
      obstruction. The prognosis of EPS is poor. The exact cause of EPS remains
      unknown. While the risk factors for EPS are not well elucidated, EPS is seen with
      increased frequency after an increased duration of PD therapy. In more than half
      the patients who develop EPS, the diagnosis is made after transfer to
      hemodialysis (HD). It is important for the HD practitioner to initiate
      surveillance in any patient at risk for EPS while maintaining a heightened index
      of suspicion for EPS in an HD patient with gastrointestinal symptoms and a
      history of previous PD therapy. Early diagnosis and prompt initiation of
      treatment is essential. Early in the course of EPS, immunosuppressive therapy
      remains the mainstay of treatment. Ultimately, parenteral nutritional support may
      be required along with surgical therapy to relieve intestinal obstruction. We
      report a case of EPS in an HD patient at our center highlighting the incidence,
      risk factors, and treatment strategies in the context of available evidence.

PMID- 19840140
TI  - Residual renal function and arterial stiffness mediated the blood pressure change
      during interdialytic weight gain in hemodialysis patients.
AB  - Volume overload is thought to be the main cause of hypertension in dialysis
      patients. However, the effect of interdialytic weight gain (IDWG) in hemodialysis
      (HD) patients, which was considered as an increase in extracellular water (ECW),
      on blood pressure (BP) change, was controversial. Our aim was to examine the
      changes in hemodynamics and arterial stiffness during IDWG in HD patients and
      attempt to explore the possible mechanism of diverse BP change. Thirty prevalent
      patients on HD were enrolled. The height, weight, BP, blood chemistry, volume
      status assessed by bioelectrical impedance analysis, hemodynamic parameters
      obtained by echocardiography, and pulse wave velocity (PWV) were collected within
      1 hour postdialysis and again just before the next dialysis session. Meanwhile,
      blood samples were drawn to analyze vasoactive hormones, including renin,
      angiotensin II, catecholamine, and endothelin. The patients' weights and ECWs
      during the next predialysis were significantly higher than those during the
      postdialysis. The BP showed no difference between postdialysis and the next
      predialysis. There was an obvious increase in cardiac output and decrease in
      total peripheral resistance as a whole during the next predialysis than that
      during postdialysis. When patients were divided into the BP increase group (BPI
      group, 13 patients) and BP decrease group (BPD group, 11 patients) according to
      the change in systolic BP higher than 10 mmHg, both groups displayed a
      significant increase in weight, ECW, cardiac output, and a decrease in total
      peripheral resistance. As compared with the BPI group, patients in the BPD group
      had significantly lower IDWG, shorter time on dialysis treatment, and higher
      residual renal function. A decrease in catecholamine and endothelin in the next
      predialysis was obvious in the BPD group. There was a significant decrease in PWV
      at the next predialysis in the BPD group while the PWV did not change
      significantly in the BPI group. Our results showed that the diverse BP change
      during IDWG was significantly affected by residual renal function, PWV, and
      vasoactive substances.

PMID- 19840141
TI  - Enhanced solute removal with intermittent, in-center, 8-hour nocturnal
      hemodialysis.
AB  - Advances in the dialysis technique and increasing urea Kt/V have not improved
      outcomes for end-stage renal disease patients maintained on hemodialysis (HD)
      therapy. Attention has, thus, focused on enhancing solute removal via prolonged
      HD sessions. A reduction in the serum levels of phosphorus and beta-2
      microglobulin (B2M) with longer HD treatments has been linked to improved patient
      outcomes. We have shown that serum phosphorus levels are significantly lowered in
      patients maintained on thrice-weekly, in-center, 8-hour nocturnal HD performed at
      a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A
      total of 8 patients participated in the study (age 45+/-7 years). Serum
      creatinine levels decreased from 9.2+/-1.9 to 3.0+/-1.0 mg/dL at 8 hours while
      serum phosphorus decreased from 5.7+/-1.9 to 2.5+/-0.7 mg/dL at 8 hours. The
      initial decrease from predialysis values to 1 hour after the start of HD was
      significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M
      decreased from 26.8+/-5.5 mg/L predialysis to 14.9+/-7.0 mg/L at 8 hours
      (P<0.01). Dialysate-side clearances of phosphorus and creatinine were 136+/-13
      and 143+/-27 cm(3)/min, respectively. Phosphorus clearances were steadily
      maintained during the 8-hour session. A total of 904+/-292 mg of phosphorus was
      removed during the 8-hour treatment, with 501+/-174 mg (55%) removed during the
      first 4 hours and the remaining 45% continuously removed during the latter one
      half of the session. The overall calculated B2M clearance was 55.1+/-40.3
      cm(3)/min using the immediate post-B2M value and 28.4+/-34.2 mg/L using the 30
      minute postdialysis value for the calculation. Serum levels of phosphorus and B2M
      decrease dramatically during an 8-hour session. Future studies are necessary to
      determine whether the enhanced solute removal with longer HD sessions translates
      into an improved outcome for HD patients.

PMID- 19840142
TI  - Cannulation and vascular access-related complications in hemodialysis: factors
      determining successful cannulation.
AB  - Little is known about cannulation of the vascular access (VA), such as the number
      of successful cannulation procedures, frequency of complications caused by
      cannulation, and VA failure. Incident patients were followed for 6 months, from
      the first successful cannulation with 2 needles--both used for the hemodialysis
      treatment. Data included patient characteristics, comorbidities, and medication.
      Vascular access characteristics included: type of VA and location, vein diameter
      assessed by Duplex ultrasound, length of the cannulation route, and maturation
      period. Longitudinal data were collected by dialysis nurses, using identical
      questionnaires, and a standardized method to register data from each dialysis
      session. Among 10 Dutch dialysis facilities, clinical data from 120 patients were
      collected from June 2005 to March 2007. The use of autogenous arteriovenous
      fistulae (P<0.001) and limited length of the cannulation route (P<0.003)
      negatively affect the outcome of cannulation and complications such as use of
      single-needle (SN) dialysis and central vein catheters (CVC). Previous use of CVC
      and SN hemodialysis were significant predictors for VA failure (P<0.0001). The
      present study demonstrated that during the first 6 months of a newly placed VA, a
      huge number of cannulation-related complications such as miscannulation, use of
      CVC, and SN dialysis are encountered. Despite the fact that guidelines
      recommended the arteriovenous fistulae as the preferred VA, cannulation-related
      complications can lead to increased morbidity. The length of the cannulation
      route positively correlates with successful cannulation. Therefore, adjusted
      cannulation techniques might be indicated to improve VA outcome.

PMID- 19840143
TI  - Indoor mold concentration in Eastern France.
AB  - Our prospective case-control study of 118 dwellings in Eastern France examined
      fungal contamination in unhealthy dwellings (n = 32) (homes with visible mold
      contamination and adverse health outcomes reported by the occupants), dwellings
      occupied by allergic patients (with medical diagnostic and positive prick-tests
      for molds) (n = 27) and matched control dwellings (n = 59). Unhealthy dwellings
      present higher airborne concentrations of Aspergillus, Penicillium, and
      Cladosporium than control dwellings, irrespective of the room sampled. Bedroom
      walls were more highly contaminated by molds than others. Dwellings occupied by
      allergic patients differed significantly for airborne concentrations of
      Penicillium only, but not for wall surface contamination, whereas bathroom walls
      were more highly contaminated than other rooms. Molecular identification of 12
      Penicillium species showed Penicillium chrysogenum and Penicillium olsonii to be
      the two main species. From the total average of molds, by impaction method,
      useful thresholds can be given: below 170 CFU/m(3), between 170 and 560 CFU/m(3),
      560 and 1000 CFU/m(3) and above 1000 CFU/m(3), respectively for dwellings with
      low, moderate, high, and very high concentrations. The latter would be considered
      a potential health hazard. PRACTICAL IMPLICATIONS: A single measure of airborne
      concentrations of molds by impaction allows to establish useful thresholds by
      social services to estimate in a objective way the housing moldiness. Excluding
      the summer period, reproducibility of this kind of measure on 3 months, in the
      fixed limits, is 94.3%. The differences in terms of biodiversity of the unhealthy
      housing and those accommodating allergic patients imply a specific approach to
      decrease fungi airborne concentrations. The biodiversity of Penicillium raises
      the problem of the use of the single extract of Penicillium chrysogenum for skin
      tests. The extent of the contaminated surfaces must be measured to assess the
      potential risk linked to spore contamination. Indeed, surface sampling mostly
      allows qualitative assessment of the environment.

PMID- 19840144
TI  - REP-PCR tracking of the origin and spread of airborne Staphylococcus aureus in
      and around chicken house.
AB  - Staphylococcus aureus was used as an indicator to study the origin and spread of
      microbial aerosol in and around chicken houses. Air samples indoor, upwind (10
      and 50 m), and downwind (10, 50, 100, 200, and 400 m) of four chicken houses were
      collected using Andersen-6 stages sampler. The concentrations of S. aureus were
      determined for every sample site. Isolation of S. aureus from chicken feces was
      performed according to the standard method. The genetic relationship among the
      isolates was determined by profiles of PCR-amplified repetitive extragenic
      palindromic (REP-PCR) elements. The results showed that the concentrations of S.
      aureus indoor of four chicken houses were higher than those upwind and downwind
      sites (P < 0.05 or P < 0.01), but there were no significant concentration
      differences among downwind sites (P > 0.05). The fingerprints and the
      phylogenetic tree indicated that a part of the S. aureus (55.6%, 10/18) isolates
      from indoor air had the same REP-PCR fingerprints as feces isolates.
      Consequently, most isolates (57.1%, 20/35) from downwind 10, 50, 100, 200, even
      400 m had the same REP-PCR fingerprints as those from indoor or feces. These data
      indicated that some isolates from downwind and indoor originated from the chicken
      feces. However, those isolates from upwind had low similarity (similarity index
      0.6-0.87) to those from indoor or feces. Therefore, the isolates upwind were not
      from the chicken feces or indoor. These results suggest that microbes in chicken
      feces can be aerosolized and spread indoor and outdoor, especially to downwind of
      the chicken houses. It should have an important epidemiological and public health
      significance. PRACTICAL IMPLICATIONS: Thus, the use of S. aureus as an indicator
      to study the origin and spread of airborne pathogens from chicken houses is
      potentially useful for enhancing public health and understanding the airborne
      epidemiology of this pathogen. Meanwhile it can provide evidence for studying the
      spreading model of airborne pathogens.

PMID- 19840145
TI  - Flow dynamics and characterization of a cough.
AB  - Airborne disease transmission has always been a topic of wide interests in
      various fields for decades. Cough is found to be one of the prime sources of
      airborne diseases as it has high velocity and large quantity of droplets. To
      understand and characterize the flow dynamics of a cough can help to control the
      airborne disease transmission. This study has measured flow dynamics of coughs
      with human subjects. The flow rate variation of a cough with time can be
      represented as a combination of gamma-probability-distribution functions. The
      variables needed to define the gamma-probability-distribution functions can be
      represented by some medical parameters. A robust multiple linear regression
      analysis indicated that these medical parameters can be obtained from the
      physiological details of a person. However, the jet direction and mouth opening
      area during a cough seemed not related to the physiological parameters of the
      human subjects. Combining the flow characteristics reported in this study with
      appropriate virus and droplet distribution information, the infectious source
      strength by coughing can be evaluated. PRACTICAL IMPLICATIONS: There is a clear
      need for the scientific community to accurately predict and control the
      transmission of airborne diseases. Transportation of airborne viruses is often
      predicted using Computational Fluid Dynamics (CFD) simulations. CFD simulations
      are inexpensive but need accurate source boundary conditions for the precise
      prediction of disease transmission. Cough is found to be the prime source for
      generating infectious viruses. The present study was designed to develop an
      accurate source model to define thermo-fluid boundary conditions for a cough. The
      model can aid in accurately predicting the disease transmission in various indoor
      environments, such as aircraft cabins, office spaces and hospitals.

PMID- 19840146
TI  - Influence of environmental characteristics and climatic factors on mites in the
      dust of air-conditioner filters.
AB  - To investigate mites in the dust of air-conditioner filters (MACF) in China, a
      total of 652 dust samples were collected from six cities: Guangzhou (n = 129),
      Nanchang (n = 127), Shanghai (n = 113), Xian (n = 93), Beijing (n = 93), and
      Shenyang (n = 79). Tarsonemus granarius was the most dominant species (87.2%).
      Dermatophagoides pteronyssinus and Dermatophagoides farinae only represented 7.0
      and 3.0% of total mites, respectively. With latitude increasing, both mite
      occurrence rate (P < 0.001) and density (mites/g dust) (P < 0.001) were
      significantly decreasing. Multivariate regression analysis suggested that the
      annual average temperature and minimum temperature in different cities had
      dominant influences on MACF density. The logistic regression analysis revealed
      that the presence of MACF was positively associated with air-conditioner age,
      utilization time and power. Wall and window type air-conditioner had higher risk
      of finding MACF than the floor type air-conditioner. As far as the cleaning
      interval time of ACF was concerned, higher risk ratio and the highest density of
      MACF were found in the time stage of >3, < or =12 months. It was also suggested
      that house type could influence the presence of MACF. A negative association
      between the house floor and the MACF prevalence was found as well. PRACTICAL
      IMPLICATIONS: Mites present in the dust of air-conditioner filters are potential
      indoor threat to asthma and allergy sufferers. In this study, we find that the
      storage mite Tarsonemus granarius is the predominant species of mites in the dust
      of air-conditioner filters (MACF). Thus, the possible clinical importance of T.
      granarius should cause more our attentions in the future. The abundance and
      distribution of MACF are also found significantly varied in different climatic
      regions of China. When we try to assess the possible risk of MACF, more
      attentions should be focused on subtropical region than temperate region. The
      influence analysis of environmental characteristics on the prevalence of MACF
      will shed light on the establishment of mite control strategy and the design of
      mite defense air-conditioner.

PMID- 19840147
TI  - Sperm chromatin structure assay as an independent predictor of fertility in vivo:
      a case-control study.
AB  - Standard sperm parameters have a limited power for prediction of the chance of
      natural conception. Recent studies have indicated that the sperm chromatin
      structure assay (SCSA) DNA fragmentation index (DFI), a measure for the fraction
      of sperms with DNA damage, is associated with fertility in vivo. The aim of this
      study was to evaluate the value of this parameter for prediction of infertility.
      One hundred and twenty-seven men from infertile couples with no known female
      factor and 137 men with proven fertility were included. Semen analysis was
      performed as recommended by the WHO. DFI was assessed using SCSA. Logistic binary
      regression was used to compute the odds ratios (OR) for infertility. As compared
      with men with a DFI <10%, men with a DFI between 10% and 20% had an increased
      risk for infertility (OR 2.5, 95% CI: 1.0-6.1). This was also true for men with a
      DFI >20% (OR 8.4; 95% CI: 3.0-23). In men with normal standard semen parameters
      (sperm concentration, motility and morphology) the OR for infertility was
      increased with DFI >20% (OR 5.1, 95% CI: 1.2-23), whereas if one of the standard
      semen parameters was abnormal, the OR for infertility was increased already at
      DFI above 10% (OR 16, 95% CI: 4.2-60). We conclude that SCSA DFI adds to the
      value of semen analysis in prediction of the chance of natural conception.

PMID- 19840148
TI  - Neural cadherin is expressed in human gametes and participates in sperm-oocyte
      interaction events.
AB  - Neural cadherin (N-cadherin) is a transmembrane glycoprotein involved in calcium
      dependent cell-cell adhesion and signalling events. The previous evidence shows N
      cadherin expression in the human gonads and gametes; however, N-cadherin
      subcellular localization in human spermatozoa and oocytes, and its involvement in
      fertilization remain to be characterized. In this study, expression of N-cadherin
      in human spermatozoa and testis was confirmed by RT-PCR and protein forms were
      identified using Western immunoblotting. N-cadherin localization in testicular
      and ejaculated spermatozoa, in cells that had undergone capacitation and
      acrosomal exocytosis, as well as in oocytes was assessed using
      immunocytochemistry. Participation of the adhesion protein in fertilization was
      evaluated using the HemiZona Assay (HZA) and the zona pellucida (ZP)-free hamster
      oocyte sperm penetration assay (SPA). Both the N-cadherin transcript and the
      mature protein form (135 kDa) were found in spermatozoa and testis. The protein
      was mainly immunolocalized in the acrosomal region of testicular, non-capacitated
      and capacitated spermatozoa, and was found in the equatorial segment after
      acrosomal exocytosis. N-cadherin was also detected in oocytes, in conjunction
      with beta-catenin, a member of the adhesion complex. Sperm incubation with anti N
      cadherin antibodies did not affect their ability to interact with homologous ZP
      in the HZA; by contrast, presence of the antibodies in the SPA led to a
      significant (p < 0.01) reduction in the percentage of penetrated oocytes. In
      conjunction, results indicate that N-cadherin is a sperm protein of testicular
      origin localized in cellular regions involved in gamete interaction. N-cadherin
      would not participate in sperm-ZP interaction, but it would have a role in sperm
      oolemma adhesion/fusion events.

PMID- 19840149
TI  - Aquaporins in the human testis and spermatozoa - identification, involvement in
      sperm volume regulation and clinical relevance.
AB  - Despite the high water-permeability of human spermatozoa, little is known about
      the identity and the role of aquaporins (AQP) in them or germ cells. Using
      ejaculates from donors, sperm AQPs were identified by western blotting followed
      by the analysis of mRNA with RT-PCR. Protein expression in the testis and
      spermatozoa was localized by immunocytochemistry. Inhibitors were used to
      investigate the involvement of aquaporins in water transport when ejaculated
      spermatozoa were swollen in medium mimicking uterine hypo-osmolality by quinine
      that blocks volume regulation. Sperm AQP7 and AQP8 in 39 infertile patients and
      11 healthy donors were quantified by flow cytometry. AQP1 was absent from
      spermatozoa. Sperm and testicular AQP7-9 had nucleotide sequences identical to
      those of somatic cells but AQP8 mRNA also showed shorter variants. AQP7 was
      expressed abundantly by round and elongated spermatids and ejaculated
      spermatozoa, AQP8 by all germ cells and spermatozoa, and AQP9 rarely by
      spermatocytes or Sertoli cells. Protein bands showed specificity by western
      blotting for AQP7 and AQP8 but not AQP9. The absence of sperm AQP9 was further
      suggested by the ineffectiveness of its inhibitor phloretin in blocking quinine
      induced swelling, but HgCl(2,) which inhibits AQP8, was effective. Sperm AQP7
      expression was correlated with progressive motility and was lower in patients
      than in donors. Sperm AQP8 expression was inversely correlated with the extent of
      sperm coiling, which is a swelling phenomenon, but showed no difference between
      patients and donors. In conclusion, AQP7 and AQP8 were identified in human
      spermatozoa and could play a role in glycerol metabolism and water transport
      respectively.

PMID- 19840150
TI  - Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and
      safety profile for this newly approved sublingually absorbed second-generation
      antipsychotic.
AB  - OBJECTIVE: To describe the efficacy and safety of asenapine for the treatment of
      schizophrenia and bipolar disorder. DATA SOURCES: The pivotal registration trials
      were accessed by querying http://www.pubmed.gov, http://www.fda.gov and
      http://www.clinicaltrials.govfor the search terms 'asenapine' or 'ORG 5222'.
      STUDY SELECTION: All available clinical reports of studies were identified, as
      well as preclinical animal and receptor affinity studies that describe potential
      mechanisms of action. Extensive documents available from the US Food and Drug
      Administration and Schering-Plough Corporation as posted on http://www.fda.gov
      provided much of this data. Product labelling also provided additional
      information. DATA EXTRACTION: Descriptions of the principal results and
      calculation of number needed to treat (NNT) and number needed to harm (NNH) for
      relevant dichotomous outcomes were extracted from the study reports and synopses.
      Additional safety outcomes subject to NNH analysis were obtained from product
      labelling. DATA SYNTHESIS: A sublingual formulation of asenapine has received
      regulatory approval for the acute treatment of schizophrenia and manic/mixed
      episodes of bipolar I disorder. Bioavailability is 35% when taken sublingually,
      but < 2% if ingested. Similar to other second-generation antipsychotics,
      asenapine's binding profile includes 5-HT2A and D2 antagonism. Binding at the
      alpha-1 adrenergic and histamine H1 receptors predicts asenapine's propensity to
      cause orthostasis and sedation in some patients. Efficacy in the treatment of
      acute schizophrenia is supported by 2 of 4 completed phase II/III randomised,
      placebo and active-controlled 6-week trials, principally at a dose of 5 mg bid.
      Responder analysis for one of the studies reveals a NNT of asenapine vs. placebo
      of six for response as defined by a minimum of a 20% decrease in the Positive and
      Negative Syndrome Scale total score from baseline, and a NNT of 8 for the
      threshold of a 30% decrease. Efficacy in the treatment of manic or mixed episodes
      of bipolar I disorder is supported by 2 of 2 completed phase III randomised,
      placebo and active-controlled 3-week trials and by a 9-week extension trial. The
      dose tested in the bipolar trials was 10 mg bid. Longer-term studies have been
      completed in patients with schizophrenia or bipolar disorder, but complete
      results have not yet been published. Asenapine has a relatively favourable
      tolerability profile. For the patients with schizophrenia, the NNH values for
      asenapine vs. placebo for commonly observed adverse reactions were 13 (95% CI 8
      30) for akathisia (10 mg bid), 20 (95% CI 13-50) for oral hypoesthesia (5 mg bid)
      and 13 (95% CI 8-32) for somnolence (5 mg bid). For patients with bipolar
      disorder, the NNH values for asenapine 5-10 mg bid vs. placebo were 6 (95% CI 5
      9) for somnolence, 13 (95% CI 9-25) for dizziness, 20 (95% CI 13-56) for extra
      pyramidal symptoms (EPS) other than akathisia and 25 (95% CI 16-71) for increased
      weight. Asenapine is associated with a lower frequency for EPS than haloperidol.
      Asenapine has a mild effect on the ECG QT interval similar to that seen with
      quetiapine. Asenapine's effect on prolactin is similar to that observed with
      olanzapine. Asenapine has a more favourable weight gain and metabolic profile
      compared with olanzapine. CONCLUSIONS: Asenapine sublingual tablets are a new
      option for the treatment of acute episodes of schizophrenia and for the treatment
      of acute manic or mixed episodes of bipolar I disorder. Although there is no
      evidence for asenapine's efficacy to be superior to currently available agents,
      asenapine's favourable weight and metabolic profile are of clinical interest. A
      caveat is that the data reviewed regarding asenapine are from its manufacturer.
      No independent studies of asenapine's efficacy or safety are available. Obstacles
      to the use of asenapine are the recommendations for twice daily dosing and the
      need to avoid food or liquids for 10 min after administration. As asenapine's
      bioavailability is very low if ingested, asenapine is unique among the
      antipsychotics, in that it needs to be swallowed to be covertly 'cheeked'.

PMID- 19840151
TI  - Changes in weight and metabolic parameters during treatment with antipsychotics
      and metformin: do the data inform as to potential guideline development? A
      systematic review of clinical studies.
AB  - BACKGROUND: Changes in weight and metabolic parameters have been commonly
      reported in patients with schizophrenia. Metformin has been evaluated in clinical
      studies to prevent or reduce weight gain and changes in metabolic parameters in
      non-diabetic subjects. We undertook a systematic review of the efficacy and
      safety of metformin in reducing weight gain and metabolic abnormalities in non
      diabetic subjects with schizophrenia or bipolar disorder taking antipsychotic
      medication to establish if these data could potentially drive guideline
      development. METHODS: Medical databases were searched using terms including
      'antipsychotic', 'atypical antipsychotic agent', 'antipsychotic agents',
      'antipsychotic-drug' and 'metformin' and 'weight'. Studies reporting weight
      and/or metabolic outcomes in non-diabetic subjects with schizophrenia and bipolar
      disorder were included regardless of methodological type and subject age.
      RESULTS: Nine randomised double-blind studies and two open cohort studies
      evaluating metformin and changes in weight in trials up to 16 weeks were
      identified. In all, 495 participants received antipsychotics (mostly olanzapine),
      and three studies were in subjects aged < 18 years. The adult studies
      predominantly utilised non-Caucasian subjects with chronic schizophrenia. Weight
      and lifestyle intervention programmes were provided to all cohorts in eight
      studies, which confounded interpretation of the data. In ten studies, the
      addition of metformin to antipsychotic treatment was associated with either
      significantly attenuated weight gain or weight loss compared with control groups.
      Nine studies measured various glucose parameters. In four studies, subjects
      prescribed metformin had significantly improved glucose parameters relative to
      controls. The two studies of metformin in patients with first-episode
      schizophrenia demonstrated the largest improvement in weight and glucose
      parameters. CONCLUSIONS: Metformin may have some value in reducing or preventing
      weight gain and changes in metabolic parameters during treatment with
      antipsychotic medication particularly in first-episode psychosis; however, it has
      been predominantly studied short-term and in non-Caucasian populations. A number
      of new trials are due to report data 2009-2013 to aid definitive interpretation
      of the role of metformin. Further longer-term studies are warranted before
      definitive guidelines can be established.

PMID- 19840152
TI  - Remembering and repeating childhood dental treatment experiences: parents, their
      children, and barriers to dental care.
AB  - BACKGROUND: Despite improvements over the past two decades, caries and its
      treatment remain a problem for Scottish children. AIM: To investigate how the
      reported childhood dental care experiences of a group of Scottish parents
      impacted upon the dental treatment they accessed for their children. STUDY
      DESIGN: In-depth, semi-structured interviews were conducted with 19 parents of
      varied age and social background whose children were referred to Dundee Dental
      Hospital for the assessment of dental extractions. Parents were encouraged to
      discuss their own and their child's experiences of dental care. The interview
      data were systematically coded using key theme headings, and summary charts
      constructed to facilitate the analysis. RESULTS: A sense of 'uneasiness' pervaded
      the parents' comments and perceptions of the dental care provided for their
      children. This was conceptualized as parents 'remembering in words' and
      'repeating through actions' their own childhood dental experiences. They
      remembered and repeated their childhood experiences by delaying dental treatment
      for themselves and their children. CONCLUSIONS: Acknowledging the influence of
      parental dental experience would help ensure that parents of young children
      access routine care for their children and themselves.

PMID- 19840153
TI  - "Your self: did you find it or did you make it?".

PMID- 19840154
TI  - Jung's dissociable psyche and the ec-static self.
AB  - Much of Jung's later work assumes that the self is an a priori phenomenon in
      which centripetal dynamics dominate. There is, however, another current in Jung's
      writings which recognizes the self to be an emergent phenomenon. This view is
      increasingly prevalent in post-Jungian discourse, and Louis Zinkin's exploration
      of a post-Jungian-constructivist model of the self can be seen as part of this
      tendency. My paper privileges an emergent understanding of the self by focusing
      on the 'unravelling', 'de-centring', centrifugal experiences of otherness in the
      psyche. It offers a post-Jungian reading of a number of writers who have been
      influenced by the psychoanalyst Jean Laplanche and proposes a model of the self
      which focuses on our fantasies, terrors and longings about coming undone and
      bringing others undone. This model is then linked to Judith Butler's
      understanding of the self as an ec-static phenomenon, in which the self is, of
      necessity, outside itself, such that 'there is no final moment in which my return
      to myself takes place'. I suggest that Jung's early clinical researches into the
      dissociability of the psyche and the clinical tools which he developed as a
      result of this work are especially suitable for engaging with these emergent,
      centrifugal dynamics.

PMID- 19840155
TI  - The self, the psyche and the world: a phenomenological interpretation.
AB  - This paper takes as its starting point Jung's definition of the self as the
      totality of the psyche. However, because the term psyche remains conceptually
      unclear the concept of the self as totality, origin and goal, even centre,
      remains vague. With reference to Heidegger's analysis of human being as Dasein,
      as well as Jung's writings, it is argued that Jung's concept of psyche is not a
      synonym for mind but is the world in which we live psychologically. An
      understanding of the psyche as existentially situated requires us to rethink some
      features of the self. For instance, the self as origin is thus not a pre
      existential integrate of pure potentiality but the original gathering of
      existence in which, and out of which, personal identity is constituted. The ego
      emerges out of the self as the development and ownership of aspects of an
      existence that is already situated and gathered. Relations between the ego and
      the self are about what is known, or admitted, and its relation with what is
      already being lived within the gathering that is existence. The self as psyche,
      origin, and centre are discussed, as well as the meaning of interiority.
      Epistemological assumptions of object relations theory are critically discussed.
      The paper also includes critical discussions of recent papers on the self.

PMID- 19840156
TI  - Elephants painting? Selfness and the emergence of self states as illustrated in
      conceptual art.
AB  - The traditional view of the self is that of a singular entity whose ground is an
      inherent function of the mind. The more recent conception of the self is moving
      toward the social constructionist concept that its ground is the discourses of
      the particular culture into which one is born. These two divergent views have
      created an irresolvable binary of inner/outer that limits their explanatory
      power. To resolve this dilemma I suggest that the abstract noun 'selfness',
      indicating a general state, should replace the representational noun 'self', that
      indicates a specific state. I will propose that 'selfness' is indeed the 'ground'
      from which our unique self states emerge. I will illustrate this with examples
      from conceptual art and will discuss its relevance to analytic theory and
      treatment.

PMID- 19840157
TI  - The enigmatic signifier and the decentred subject.
AB  - War, genocide, economic upheaval and terrorism have crushed belief in endlessly
      'enlightened' progress. We more and more doubt the teleological nature of
      psychological events, including the activity of a Self or centre that guides the
      development of the subject. There is a growing view of a 'decentred' subject that
      develops in the face of an enigmatic Otherness. Jean Laplanche has created an
      extensive metapsychology describing this situation, emphasizing the original
      helplessness of an infant who is bathed in enigmatic messages from its very
      beginnings. These messages from the adult other are often sexualized, and are
      partly or largely unconscious to the sender. Laplanche calls this situation
      'primal seduction'. The immature human cannot fully metabolize such adult
      messages, and through 'primal repression' they remain as the unconscious core of
      subjectivity. They disrupt psychological life, conveying a sense of signifying
      something to the subject. What they signify is an enigma, like finding a
      hieroglyph in the desert. The story of relationships and culture is the story of
      our repeated attempts to translate them, to respond to them. An analytic case
      illustrates these concepts as they appear in the transference, first as gaps and
      monsters, and then in the crucial and surprising appearance of transformative
      laughter. The vicissitudes of the clinical situation illustrate the vital
      importance of the enigmatic signifier in the development of the subject.

PMID- 19840158
TI  - Union and separation in the therapy of pervasive developmental disorders and
      ADHD.
AB  - This paper discusses the characteristics of psychotherapy for pervasive
      developmental disorders (PDD) in the context of the curative effects of the
      movement of images. The 'autistic spectrum' is widened here and includes not only
      PDD, but also ADHD. The main common characteristic in these two sets of disorders
      seems to be the lack of a subject, which manifests itself as the absence of
      awareness of otherness and difficulties with boundaries and language. In these
      cases a normal psychotherapy is ineffective as it presupposes an established
      subject. However a psychotherapeutic approach with these patients can contribute
      to the emergence of a subject. In severe cases the process of union and
      separation which is enacted either in the therapeutic relationship or in symbolic
      play leads to the birth of a subject, and of language. In milder cases, such as
      ADHD, the moments of separation and confrontation with the therapist suffice. I
      will discuss a case of my own with Asperger's syndrome in which union and
      separation in the play therapy occurred simultaneously. This indicates that union
      and separation are not a consecutive process, but are simultaneous and lead to
      dialectical movement. However, in neurotic cases with an established subjectivity
      the symbolic meaning of image plays a central role. This corresponds to Jung's
      understanding of image in alchemy.

PMID- 19840159
TI  - The embodied self: thinking psychoanalytically in a time of 'science'.
AB  - In order to be relevant in our 'scientific' times, it is necessary that we
      psychoanalysts situate our ideas in thoughtful and respectful relationship to
      neighbouring disciplines such as genetics, cultural studies, and neuro-anatomy.
      In this paper I suggest that, although psychoanalysis still continues to have
      valuable contributions to make to the understanding of human sexual experience
      and behaviour, in order to make these contributions relevant we must tune in with
      openness to the challenges posed by the unfolding discoveries in the other
      disciplines that grapple with the arena of human sexuality. I will suggest ways
      in which research on sexual desire and gender identity may be assimilated into
      psychoanalytic thinking and give some examples of its use in analytic practice.

PMID- 19840160
TI  - Ghost and self: Jung's paradigm shift and a response to Zinkin.
AB  - Zinkin's lucid challenge to Jung makes perfect sense. Indeed, it is the
      implications of this 'making sense' that this paper addresses. For Zinkin's
      characterization of the 'self' takes it as a 'concept' requiring coherence; a
      variety of abstract non-contextual knowledge that itself has a mythical heritage.
      Moreover, Zinkin's refinement of Jung seeks to make his work fit for the
      scientific paradigm of modernity. In turn, modernity's paradigm owes much to
      Newton's notion of knowledge via reductionism. Here knowledge or investigation is
      divided up into the smallest possible units with the aim of eventually putting it
      all together into 'one' picture of scientific truth. Unfortunately,
      'reductionism' does not do justice to the resonant possibilities of Jung's
      writing. These look forward to a new scientific paradigm of the twenty-first
      century, of the interactive 'field', emergence and complexity theory. The paper
      works paradoxically by discovering Zinkin's 'intersubjective self' after all, in
      two undervalued narratives by Jung, his doctoral thesis and a short late ghost
      story. However, in the ambivalences and radical fictional experimentation of
      these fascinating texts can be discerned an-Other self, one both created and
      found.

PMID- 19840170
TI  - Paternally derived immune priming for offspring in the red flour beetle,
      Tribolium castaneum.
AB  - 1. Parasitized females in mammals, fish and birds can enhance the immune defence
      of their offspring by transferring specific antibodies for the embryo. Likewise,
      social insect mothers transfer immunity despite the fact that invertebrates lack
      antibodies. 2. Female trans-generational immune priming is consistent with
      parental investment theory, because mothers invest more into rearing their
      offspring than fathers. However, when immune priming is not directly linked to
      parental care, as is often the case in insects that abandon their eggs after
      oviposition, both sexes might benefit from protecting their offspring. 3. Using
      the red flour beetle, Tribolium castaneum, we show that after parental exposure
      to heat-killed bacteria, trans-generational immune priming occurs through fathers
      as well as mothers. 4. This novel finding challenges the traditional view that
      males provide only genes to their offspring in species without paternal care, and
      raises the possibility of a division of tasks with respect to immune protection
      between parents.

PMID- 19840171
TI  - Can compensatory culling offset undesirable evolutionary consequences of trophy
      hunting?
AB  - 1. There is growing concern about the evolutionary consequences of human
      harvesting on phenotypic trait quality in wild populations. Undesirable
      consequences are especially likely with trophy hunting because of its strong bias
      for specific phenotypic trait values, such as large antlers in cervids and horns
      in bovids. Selective hunting can cause a decline in a trophy trait over time if
      it is heritable, thereby reducing the long-term sustainability of the activity
      itself. 2. How can we build a sustainable trophy hunting tradition without the
      negative trait-altering effects? We used an individual-based model to explore
      whether selective compensatory culling of 'low quality' individuals at an early
      life stage can facilitate sustainability, as suggested by information from
      managed game populations in eastern and central Europe. Our model was rooted in
      empirical data on red deer, where heritability of sexual ornaments has been
      confirmed and phenotypic quality can be assessed by antler size in individuals as
      young as 1 year. 3. Simulations showed that targeted culling of low-quality
      yearlings could counter the selective effects of trophy hunting on the
      distribution of the affected trait (e.g. antler or horn size) in prime-aged
      individuals. Assumptions of trait heritability and young-to-adult correlation
      were essential for compensation, but the model proved robust to various other
      assumptions and changes to input parameters. The simulation approach allowed us
      to verify responses as evolutionary changes in trait values rather than short
      term consequences of altered age structure, density and viability selection. 4.
      We conclude that evolutionarily enlightened management may accommodate trophy
      hunting. This has far reaching implications as income from trophy hunting is
      often channelled into local conservation efforts and rural economies. As an
      essential follow-up, we recommend an analysis of the effects of trophy hunting in
      conjunction with compensatory culling on the phenotypic and underlying genetic
      variance of the trophy trait.

PMID- 19840172
TI  - Does dispersal control population densities in advection-dominated systems? A
      fresh look at critical assumptions and a direct test.
AB  - 1. In advection-dominated systems (both freshwater and marine), population
      dynamics are usually presumed to be dominated by the effects of migrants
      dispersing by advection, especially over the small spatial scales at which
      populations can be studied, but few studies have tested this presumption. We
      tested the hypothesis that benthic densities are controlled by densities of
      dispersers for two aquatic insects in upland streams. 2. Our study animals were
      two species of caddisflies (Hydropsychidae), which become sedentary filter
      feeders following settlement onto substrata. Densities of dispersers in the drift
      (advective dispersal) were quantified using nets placed along the upstream edges
      of riffles, where the latter abruptly abutted a slower, upstream run. Settlement
      was estimated at each site using brick pavers, half of which had been fenced to
      prevent colonization of their top surfaces by walking hydropsychids, thus
      allowing us to distinguish also the mode of movement during settlement. 3. First
      through fifth instars of two species, Smicrophylax sp. AV2 and Asmicridea sp.
      AV1, were abundant and showed disparate results. Drift and settlement were
      relatively strongly related for Smicrophylax. The best fit lines were shown by
      second and third instars settling on plain bricks, suggesting that drift played a
      strong role in settlement, but that some drifters dropped to the bottom and
      located substrata by walking. Quantile regression suggested that drift sets
      limits to settlement in this species and that settlement success was highly
      variable. In contrast, settlement by Asmicridea was poorly related to drift;
      settlers were mainly individuals re-dispersing within sites. 4. Smicrophylax
      densities appear to be controlled by dispersal from upstream, but benthic density
      of Asmicridea is more likely linked to local demography. Our data demonstrate the
      dangers of assuming that supposedly drift-prone species can all be modelled in
      the same way. Alternative models emphasizing little or different kinds of
      movement should be considered. Variability in oviposition coupled with weak
      dispersal, for example, is a viable alternative hypothesis to explain variation
      in benthic density along channels. Moreover, the constraints on settlement of
      Smicrophylax show that immigrants into sites can be in short supply, an
      hypothesis rarely considered in stream research.

PMID- 19840173
TI  - The physiology of predator stress in free-ranging prey.
AB  - Ecologists have only begun to understand the physiological mechanisms underlying
      individual- and population-level responses of prey- to predator-related stress.
      Sheriff, Krebs and Boonstra advance this field by providing evidence that
      predator-induced increases in glucorticoid concentrations in wild female snowshoe
      hares (Lepus americanus) impact both litter size and offspring condition. They
      hypothesize that the glucocorticoid-mediated effects on reproduction provides an
      adaptive benefit: mothers 'programming' their offspring to be timid and risk
      averse in high-risk environments should increase their survival probability. This
      research illuminates the connection between stress physiology and population
      level changes and demonstrates the surprisingly far-reaching impact of predation
      risk.

PMID- 19840174
TI  - Habitat-specific demography and source-sink dynamics in a population of Siberian
      jays.
AB  - 1. There are a number of models describing population structure, many of which
      have the capacity to incorporate spatial habitat effects. One such model is the
      source-sink model, that describes a system where some habitats have a natality
      that is higher than mortality (source) and others have a mortality that exceeds
      natality (sink). A source can be maintained in the absence of migration, whereas
      a sink will go extinct. 2. However, the interaction between population dynamics
      and habitat quality is complex, and concerns have been raised about the validity
      of published empirical studies addressing source-sink dynamics. In particular,
      some of these studies fail to provide data on survival, a significant component
      in disentangling a sink from a low quality source. Moreover, failing to account
      for a density-dependent increase in mortality, or decrease in fecundity, can
      result in a territory being falsely assigned as a sink, when in fact, this
      density-dependent suppression only decreases the population size to a lower
      level, hence indicating a 'pseudo-sink'. 3. In this study, we investigate a long
      term data set for key components of territory-specific demography (mortality and
      reproduction) and their relationship to habitat characteristics in the
      territorial, group-living Siberian jay (Perisoreus infaustus). We also assess
      territory-specific population growth rates (r), to test whether spatial
      population dynamics are consistent with the ideas of source-sink dynamics. 4.
      Although average mortality did not differ between sexes, habitat-specific
      mortality did. Female mortality was higher in older forests, a pattern not
      observed in males. Male mortality only increased with an increasing amount of
      open areas. Moreover, reproductive success was higher further away from human
      settlement, indicating a strong effect of human-associated nest predators. 5.
      Averaged over all years, 76% of the territories were sources. These territories
      generally consisted of less open areas, and were located further away from human
      settlement. 6. The source-sink model provides a tool for modelling demography in
      distinct habitat patches of different quality, which can aid in identifying key
      habitats within the landscape, and thus, reduce the risk of implementing unsound
      management decisions.

PMID- 19840175
TI  - Evidence of the co-circulation of enteric viruses in sewage and in the population
      of Greater Cairo.
AB  - AIMS: To characterize major enteric viruses (enterovirus, rotavirus, norovirus,
      astrovirus and adenovirus) in the sewage of Greater Cairo and to compare the
      results with clinical data collected during the same period. METHODS AND RESULTS:
      Seventy-two sewage samples from two waste water treatment plants were collected
      from April 2006 through February 2007. Enteroviruses, noroviruses (NoVs) and
      rotaviruses (RVs) were detected by RT-PCR in 22%, 18% and 8.3% of the samples,
      respectively. No adenovirus and astrovirus was detected. G2P[8], G9P[8], G1P[8],
      G2P[4] and rare G12 RV isolates were detected in the environment as well as a
      bovine RV. The environmental NoV strains mostly belonged to genogroup I (84%).
      Rotaviruses and some of the NoVs were similar to those found in the clinical
      samples at the same time. CONCLUSIONS: The comparison of environmental and
      clinical data suggests that similar RV and NoV isolates were circulating in the
      environment and in the population during the same period. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Few studies have investigated the prevalence and the epidemiology
      of RVs and NoVs in Cairo. This work is the first to establish a correlation
      between viral gastroenteritis and the concomitant presence of enteric viruses in
      the environment for Greater Cairo where combined environmental and clinical
      surveys should help to prevent infections caused by these major pathogens.

PMID- 19840176
TI  - Phylogenetic relationships of Riemerella anatipestifer serovars and related taxa
      and an evaluation of specific PCR tests reported for R. anatipestifer.
AB  - AIMS: The aims of the present investigation were to characterize and identify
      serovars of Riemerella anatipestifer and Riemerella-like isolates genetically and
      to test the specificity of PCR tests reported for the identification of R.
      anatipestifer. METHODS AND RESULTS: A total of 50 isolates from poultry
      tentatively classified with Riemerella anatipestifer were characterized
      genetically by partial sequencing of rpoB and by nearly full sequencing of the
      16S rRNA gene for selected isolates. The results obtained were compared with the
      data from 13 reference strains by phylogenetic analysis. A total of 41 isolates
      were identified as R. anatipestifer, three as Wautersiella falsenii like, a
      single isolate as Pelistega europaea, while five isolates were classified as new,
      unnamed taxa. None of the reported PCR tests for identification of R.
      anatipestifer were found specific. CONCLUSIONS: Characterization of R.
      anatipestifer and related bacteria by traditional methods is often inconclusive
      because of inconsistent reactions and phenotypic diversity. For the same reason,
      gene sequencing and phylogenetic analysis are essential to allow proper
      classification and identification as demonstrated in the present study.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The present investigations demonstrated
      that isolates of R. anatipestifer are often misidentified, and that new serovars
      should not be accepted unless they have been properly characterized by relevant
      genetic methods such as gene sequencing. In addition, we showed that the
      published PCR tests are not specific for this species. Finally, two new taxa were
      outlined, the final taxonomic positions of which remain to be identified.

PMID- 19840177
TI  - Production of cell-cell signalling molecules by bacteria isolated from human
      chronic wounds.
AB  - AIM: To (i) identify chronic wound bacteria and to test their ability to produce
      acyl-homoserine-lactones (AHLs) and autoinducer-2 (AI-2) cell-cell signalling
      molecules and (ii) determine whether chronic wound debridement samples might
      contain these molecules. METHODS AND RESULTS: Partial 16S rRNA gene sequencing
      revealed the identity of 46 chronic wound strains belonging to nine genera. Using
      bio-reporter assays, 69.6% of the chronic wound strains were inferred to produce
      AI-2, while 19.6% were inferred to produce AHL molecules. At least one strain
      from every genus, except those belonging to the genera Acinetobacter and
      Pseudomonas, were indicated to produce AI-2. Production of AI-2 in batch cultures
      was growth-phase dependent. Cross-feeding assays demonstrated that AHLs were
      produced by Acinetobacter spp., Pseudomonas aeruginosa and Serratia marcescens.
      Independent from studies of the bacterial species isolated from wounds, AHL
      and/or AI-2 signalling molecules were detected in 21 of 30 debridement samples of
      unknown microbial composition. CONCLUSION: Chronic wound bacteria produce cell
      cell signalling molecules. Based on our findings, we hypothesize that resident
      species generally produce AI-2 molecules, and aggressive transient species
      associated with chronic wounds typically produce AHLs. Both these classes of cell
      cell signals are indicated to be present in human chronic wounds. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Interbacterial cell-cell signalling may be an important
      factor influencing wound development and if this is the case, the presence of
      AHLs and AI-2 could be used as a predictor of wound severity. Manipulation of
      cell-cell signalling may provide a novel strategy for improving wound healing.

PMID- 19840178
TI  - Production of enterocin A by Enterococcus faecium MMRA isolated from 'Rayeb', a
      traditional Tunisian dairy beverage.
AB  - AIMS: Characterization and purification of a bacteriocin produced by a wild
      Enterococcus faecium strain, isolated from a Tunisian traditional fermented milk.
      METHODS AND RESULTS: Enterococcus faecium MMRA was selected on the basis of its
      strong anti-Listeria activity. The antibacterial activity was sensitive to
      proteases, confirming its proteinaceous nature. It was extremely heat stable (15
      min at 121 degrees C), remained active over a wide pH range (2-12), and also
      after treatment with lipase, amylase, organic solvents, detergents,
      lyophilisation and long-term storage at -20 degrees C. Production of the
      bacteriocin occurred throughout the logarithmic growth phase, it did not adhere
      to the surface of the producer cells and the mode of action was bactericidal.
      After partial purification of the active supernatants, a 4-kDa band with
      antibacterial activity was revealed by SDS-PAGE electrophoresis and bioassay.
      Tryptic digestion followed by MALDI-TOF mass spectrometry identified the peptide
      as enterocin A. CONCLUSIONS: The inhibitory activity of Ent. faecium MMRA, a wild
      strain isolated from the artisan dairy beverage 'Rayeb', is due to the synthesis
      of an enterocin A. SIGNIFICANCE AND IMPACT OF THE STUDY: Traditional fresh
      Tunisian fermented dairy products are generally manufactured with raw milk that
      can be used as a source of uncharacterized wild lactic acid bacteria strains. To
      our knowledge, this is the first report on the isolation of an enterocin A
      producing Ent. faecium from 'Rayeb'. This bacteriocin or the producing strain
      might have a promising potential in biopreservation to enhance the hygienic
      quality of this dairy product.

PMID- 19840179
TI  - Endoglucanase activities and growth of marine-derived fungi isolated from the
      sponge Haliclona simulans.
AB  - AIMS: The conversion of cheap cellulosic biomass to more easily fermentable
      sugars requires the use of costly cellulases. We have isolated a series of marine
      sponge-derived fungi and screened these for cellulolytic activity to determine
      the potential of this unique environmental niche as a source of novel cellulase
      activities. METHODS AND RESULTS: Fungi were isolated from the marine sponge
      Haliclona simulans. Phylogenetic analysis of these and other fungi previously
      isolated from H. simulans showed fungi from three phyla with very few duplicate
      species. Cellulase activities were determined using plate-based assays using
      different media and sea water concentrations while extracellular cellulase
      activities were determined using 3,5-dinitrosalicylic acid (DNSA)-based assays.
      Total and specific cellulase activities were determined using a range of
      incubation temperatures and compared to those for the cellulase overproducing
      mutant Hypocrea jecorina QM9414. Several of the strains assayed produced total or
      relative endoglucanase activities that were higher than H. jecorina, particularly
      at lower reaction temperatures. CONCLUSIONS: Marine sponges harbour diverse
      fungal species and these fungi are a good source of endoglucanase activities.
      Analysis of the extracellular endoglucanase activities revealed that some of the
      marine-derived fungi produced high endoglucanase activities that were especially
      active at lower temperatures. SIGNIFICANCE AND IMPACT OF THE STUDY: Marine
      derived fungi associated with coastal marine sponges are a novel source of highly
      active endoglucanases with significant activity at low temperatures and could be
      a source of novel cellulase activities.

PMID- 19840180
TI  - Brettanomyces bruxellensis evolution and volatile phenols production in red wines
      during storage in bottles.
AB  - AIMS: The presence of Brettanomyces bruxellensis is an important issue during
      winemaking because of its volatile phenols production capacities. The aim of this
      study is to provide information on the ability of residual B. bruxellensis
      populations to multiply and spoil finished wines during storage in bottles.
      METHODS AND RESULTS: Several finished wines were studied. Brettanomyces
      bruxellensis populations were monitored during two and a half months, and
      volatile phenols as well as chemical parameters regularly determined. Variable
      growth and volatile phenols synthesis capacities were evidenced, in particularly
      when cells are in a noncultivable state. In addition, the volatile phenol
      production was clearly shown to be a two-step procedure that could strongly be
      correlated to the physiological state of the yeast population. CONCLUSIONS: This
      study underlines the importance of minimizing B. bruxellensis populations at the
      end of wine ageing to reduce volatile phenols production risk once the wine in
      bottle. Moreover, the physiological state of the yeast seems to have an important
      impact on ethyl-phenols production, hence demonstrating the importance of taking
      into account this parameter when analysing wine spoilage risks. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Little data exist about the survival of B. bruxellensis once
      the wine in bottle. This study provides information on the alteration risks
      encountered during wine storage in bottle and reveals the importance of carrying
      on further studies to increase the knowledge on B. bruxellensis physiology.

PMID- 19840181
TI  - Rapid detection and differentiation of Erysipelothrix spp. by a novel multiplex
      real-time PCR assay.
AB  - AIM: The aim of this study was to develop a multiplex real-time PCR assay for the
      identification and discrimination of Erysipelothrix rhusiopathiae, tonsillarum
      and Erysipelothrix sp. strain 2 for direct detection of Erysipelothrix spp. from
      animal specimens. METHODS AND RESULTS: A primer set and three species-specific
      probes with different end labelling were designed from the noncoding region
      downstream of the 5S rRNA coding region. The sensitivity, specificity and
      repeatability of the assay were validated by analysing 27 Erysipelothrix spp.
      reference serotype strains and ten septicemia-associated non-Erysipelothrix spp.
      bacterial isolates. Cross-reactivity with Erysipelothrix sp. strain 1 was not
      observed with any of the primer probe combinations. The detection limit was
      determined to be <10 colony forming units and as low as one genome equivalent per
      PCR . Further evaluation of the Erysipelothrix spp. multiplex PCR was performed
      by comparing an enrichment isolation culture method and a conventional
      differential PCR on 15 samples from pigs experimentally inoculated with
      Erysipelothrix spp. and 22 samples from pigs with suspected natural infection.
      CONCLUSION: The multiplex real-time PCR assay was found to be simple, rapid,
      reliable, specific and highly sensitive. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The developed real-time multiplex PCR assay does not require cumbersome and
      lengthy cultivation steps prior to DNA extraction, obtained comparable results to
      enrichment isolation, and will be useful in diagnostic laboratories for rapid
      detection of Erysipelothrix spp.

PMID- 19840182
TI  - LNA probes in a real-time TaqMan PCR assay for genotyping of Giardia duodenalis
      in wastewaters.
AB  - AIMS: This study describes an approach for genotyping Giardia cysts obtained from
      wastewater treatment plants (WTPs) in Spain using real-time PCR (qPCR) in
      combination with immunomagnetic beads. METHODS AND RESULTS: A 50-cycle
      amplification of a 74-bp fragment of the Giardia beta-giardin gene was adopted
      from a previous qPCR method. Additionally, two locked nucleic acid (LNA) probes
      were designed (LNA P434 P1 for assemblage A and LNA P434 H3 for assemblage B).
      All 16 wastewater samples analysed were positive with the immunofluorescence
      assay (IFA). Assemblage A was detected in all WTP samples using primer-LNA probe
      P434 P1 set. Giardia duodenalis identification was confirmed by PCR-RFLP analysis
      and sequencing of the beta-giardin gene in the water samples found positive by
      IFA and qPCR. Among the 16 assemblage A isolates that were sequenced, two
      subtypes were identified; 11 corresponded to the A2 subgenotype, whereas three
      corresponded to the subgenotype A3. A mixture of subgenotypes was found in the
      remaining two isolates. CONCLUSIONS: The newly developed qPCR assays were able to
      discern G. duodenalis assemblages A and B in wastewater. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The real-time PCR assays provided a rapid method for detection and
      one-step genotyping of G. duodenalis from wastewater samples, and its application
      would contribute to understanding the distribution and abundance of G. duodenalis
      assemblages A and B in wastewater.

PMID- 19840183
TI  - Antagonistic effect of acetic acid and salt for inactivating Escherichia coli
      O157:H7 in cucumber puree.
AB  - AIM: This study was conducted to investigate the effects of acetic acid alone or
      combined with salt for inhibiting Escherichia coli O157:H7 in cucumber puree
      during storage time at 5 and 22 degrees C. METHODS AND RESULTS: Samples at
      various concentrations were prepared by the addition of acetic acid (0%, 0.25%,
      0.5%, 0.75%, 1%, 2%, 2.5%, or 3%) along with NaCl (0% or 3%) and pureed cucumber
      (50% or 94%). The effect of storage temperature (5 and 22 degrees C) on the
      survival of E. coli O157:H7 was also tested. The numbers of E. coli O157:H7 were
      reduced as the amount of acetic acid increased (P < 0.01) and rate of reduction
      was more rapid at 22 degrees C than at 5 degrees C. Combinations of acetic acid
      and salt were less effective at killing E. coli O157:H7 in simulated pickled
      cucumber samples stored at 5 and 22 degrees C than did treatment of acetic acid
      alone. The concentration of pureed cucumber affected the reduction rate of E.
      coli O157:H7. When stored at 5 degrees C, E. coli O157:H7 survived for up to 23
      days in a mixture of 94% cucumber puree, 1% acetic acid, and 3% NaCl.
      CONCLUSIONS: There was the antagonistic effect of acetic acid and 3% NaCl with
      regard to the reduction of E. coli O157:H7. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Our results suggest that pickled cucumbers prepared with at least 2% acetic acid
      and stored at room temperature (22 degrees C) after 3 days storage can free from
      E. coli O157:H7 without heating.

PMID- 19840184
TI  - Pulmonary valve repair: an option for an emerging problem.
AB  - In this report, we present our experience with successful pulmonary valve repair
      for pulmonary regurgitation in a 15-year-old patient who had undergone
      percutaneous pulmonary balloon valvuloplasty for pulmonary stenosis in the
      neonatal period. The pathological findings and the technique of repair are
      described in detail as the number of such patients is expected to increase in
      future.

PMID- 19840185
TI  - Left coronary artery compression caused by a false aneurysm expansion after
      perforation of type A aortic dissection.

PMID- 19840186
TI  - A case of primary cardiac angiosarcoma: extensive right atrial wall
      reconstruction with autologous pericardium.
AB  - Primary cardiac angiosarcoma is a rare and aggressive tumor. Diagnosis is usually
      late because of the rarity of the lesion and the nonspecific clinical symptoms.
      We report the case of a 48-year-old man affected by angiosarcoma of the right
      atrium who presented with subacute cardiac tamponade. Extensive resection of the
      atrial wall infiltrated by the tumor, followed by autologous pericardial free
      atrial wall reconstruction, was successfully carried out. In spite of the optimal
      early outcome, the patient died 15 months later because of multiple osteal
      metastases.

PMID- 19840187
TI  - Robotically assisted ablation produces more rapid and greater signal attenuation
      than manual ablation.
AB  - INTRODUCTION: Robotic remote catheter ablation potentially provides improved
      catheter-tip stability, which should improve the efficiency of radiofrequency
      energy delivery. Percentage reduction in electrogram peak-to-peak voltage has
      been used as a measure of effectiveness of ablation. We tested the hypothesis
      that improved catheter-tip stability of robotic ablation can diminish signals to
      a greater degree than manual ablation. METHODS: In vivo NavX maps of 7 pig atria
      were constructed. Separate lines of ablation were performed robotically and
      manually, recording pre- and postablation peak-to-peak voltages at 10, 20, 30,
      and 60 seconds and calculating signal amplitude reduction. Catheter ablation
      settings were constant (25W, 50 degrees , 17 mL/min, 20-30 g catheter tip
      pressure). The pigs were sacrificed and ablation lesions correlated with NavX
      maps. RESULTS: Robotic ablation reduced signal amplitude to a greater degree than
      manual ablation (49 +/- 2.6% vs 29 +/- 4.5% signal reduction after 1 minute [P =
      0.0002]). The mean energy delivered (223 +/- 184 J vs 231 +/- 190 J, P = 0.42),
      power (19 +/- 3.5 W vs 19 +/- 4 W, P = 0.84), and duration of ablation (15 +/- 9
      seconds vs 15 +/- 9 seconds, P = 0.89) was the same for manual and robotic. The
      mean peak catheter-tip temperature was higher for robotic (45 +/- 5 degrees C vs
      42 +/- 3 degrees C [P < 0.0001]). The incidence of >50% signal reduction was
      greater for robotic (37%) than manual (21%) ablation (P = 0.0001). CONCLUSION:
      Robotically assisted ablation appears to be more effective than manual ablation
      at signal amplitude reduction, therefore may be expected to produce improved
      clinical outcomes.

PMID- 19840189
TI  - Breast cancer cell growth inhibition by phenethyl isothiocyanate is associated
      with down-regulation of oestrogen receptor-alpha36.
AB  - The dietary isothiocyanates (ITCs) exhibit strong chemopreventive activities for
      a variety of neoplasms including breast cancer. However, the molecular mechanisms
      underlying ITC function in breast cancer cells have not been well established.
      Here, we found that phenethyl isothiocyanate (PEITC) acted more potently than the
      'pure' anti-oestrogen ICI 182,780 to inhibit the growth of oestrogen receptor
      (ER)(+) breast cancer MCF7 and H3396 cells and ER(-) MDA-MB-231 and SK-BR-3
      cells. PEITC reduced the steady state levels of ER-alpha and its novel variant,
      ER-alpha36 in a dose-and time-dependent manner and inhibited oestrogen-induced
      activation of the mitogen activated protein kinase/ERK 1/2 signaling pathway.
      However, ICI 182,780 that is potent in destabilization of ER-alpha protein,
      failed to down-regulate ER-alpha36. Our results thus demonstrated that PEITC
      functions as a more potent ER-alpha'disruptor' than the well-known ICI 182,780 to
      abrogate ER-mediated mitogenic oestrogen signaling in breast cancer cells, which
      provides a molecular explanation for the strong growth inhibitory activity of
      ITCs in breast cancer cells, and a rational for further exploration of ITCs as
      chemopreventive agents for human mammary carcinogenesis.

PMID- 19840188
TI  - Bone regeneration: the stem/progenitor cells point of view.
AB  - After bone injuries, several molecular mechanisms establish bone repair from
      stem/progenitor cells. Inflammation factors attract regenerative cells which
      expand and differentiate in order to build up a bone highly similar to that
      before injury. Bone marrow (BM) mesenchymal stem cells (MSCs) as skeletal stem
      cells and endothelial progenitors (EPCs) are at the origin of such reparation
      mechanisms. However, discrepancies exist about their identities. Although
      cultured MSCs are extensively described, their in vivo native forms are poorly
      known. In addition, recent experiments show that several types of EPC exist. We
      therefore review up-to-date data on the characterization of such stem/progenitor
      cells and propose a new point of view of their function in bone regeneration.

PMID- 19840190
TI  - Telomere attrition and genomic instability in xeroderma pigmentosum type-b
      deficient fibroblasts under oxidative stress.
AB  - Xeroderma pigmentosum B (XPB/ERCC3/p89) is an ATP-dependent 3'-->5' directed DNA
      helicase involved in basal RNA transcription and the nucleotide excision repair
      (NER) pathway. While the role of NER in alleviating oxidative DNA damage has been
      acknowledged it remains poorly understood. To study the involvement of XPB in
      repair of oxidative DNA damage, we utilized primary fibroblasts from a patient
      suffering from XP with Cockayne syndrome and hydrogen peroxide (H(2)O(2)) to
      induce oxidative stress. Mutant cells retained higher viability and cell cycle
      dysfunction after H(2)O(2) exposure. Cytokinesis blocked micronucleus assay
      revealed increased genome instability induced by H(2)O(2). Single cell gel
      electrophoresis (comet) assay showed that the missense mutation caused a reduced
      repair capacity for oxidative DNA damage. Mutant fibroblasts also displayed
      decreased population doubling rate, increased telomere attrition rate and early
      emergence of senescent characteristics under chronic low dose exposure to
      H(2)O(2). Fibroblasts from a heterozygous individual displayed intermediate
      traits in some assays and normal traits in others, indicating possible copy
      number dependence. The results show that a deficiency in functional XPB
      paradoxically renders cells more sensitive to the genotoxic effects of oxidative
      stress while reducing the cytotoxic effects. These findings have implications in
      the mechanisms of DNA repair, mutagenesis and carcinogenesis and ageing in normal
      physiological systems.

PMID- 19840191
TI  - Assessment of tumour hypoxia for prediction of response to therapy and cancer
      prognosis.
AB  - Tumour cells exploit both genetic and adaptive means to survive and proliferate
      in hypoxic microenvironments, resulting in the outgrowth of more aggressive
      tumour cell clones. Direct measurements of tumour oxygenation, and surrogate
      markers of the hypoxic response in tumours (for instance, hypoxia inducible
      factor-1alpha, carbonic anhydrase 9 and glucose transporter-1) are well
      established prognostic markers in solid cancers. However, individual markers do
      not fully capture the complex, dynamic and heterogeneous hypoxic response in
      cancer. To overcome this, expression profiling has been employed to identify
      hypoxia signatures in cohorts or models of human cancer. Several of these hypoxia
      signatures have demonstrated prognostic significance in independent cancer
      datasets. Nevertheless, individual hypoxia markers have been shown to predict the
      benefit from hypoxia-modifying or anti-angiogenic therapies. This review aims to
      discuss the clinical impact of translational work on hypoxia markers and to
      explore future directions for research in this area.

PMID- 19840192
TI  - Ankyrin protein networks in membrane formation and stabilization.
AB  - In eukaryotic cells, ankyrins serve as adaptor proteins that link membrane
      proteins to the underlying cytoskeleton. These adaptor proteins form protein
      complexes consisting of integral membrane proteins, signalling molecules and
      cytoskeletal components. With their modular architecture and ability to interact
      with many proteins, ankyrins organize and stabilize these protein networks,
      thereby establishing the infrastructure of membrane domains with specialized
      functions. To this end, ankyrin collaborates with a number of proteins including
      cytoskeletal proteins, cell adhesion molecules and large structural proteins.
      This review addresses the targeting and stabilization of protein networks related
      to ankyrin interactions with the cytoskeletal protein beta-spectrin, L1-cell
      adhesion molecules and the large myofibrillar protein obscurin. The significance
      of these interactions for differential targeting of cardiac proteins and neuronal
      membrane formation is also presented. Finally, this review concludes with a
      discussion about ankyrin dysfunction in human diseases such as haemolytic
      anaemia, cardiac arrhythmia and neurological disorders.

PMID- 19840193
TI  - Aldehyde dehydrogenase activity promotes survival of human muscle precursor
      cells.
AB  - Aldehyde dehydrogenases (ALDH) are a family of enzymes that efficiently detoxify
      aldehydic products generated by reactive oxygen species and might therefore
      participate in cell survival. Because ALDH activity has been used to identify
      normal and malignant cells with stem cell properties, we asked whether human
      myogenic precursor cells (myoblasts) could be identified and isolated based on
      their levels of ALDH activity. Human muscle explant-derived cells were incubated
      with ALDEFLUOR, a fluorescent substrate for ALDH, and we determined by flow
      cytometry the level of enzyme activity. We found that ALDH activity positively
      correlated with the myoblast-CD56(+) fraction in those cells, but, we also
      observed heterogeneity of ALDH activity levels within CD56-purified myoblasts.
      Using lentiviral mediated expression of shRNA we demonstrated that ALDH activity
      was associated with expression of Aldh1a1 protein. Surprisingly, ALDH activity
      and Aldh1a1 expression levels were very low in mouse, rat, rabbit and non-human
      primate myoblasts. Using different approaches, from pharmacological inhibition of
      ALDH activity by diethylaminobenzaldehyde, an inhibitor of class I ALDH, to cell
      fractionation by flow cytometry using the ALDEFLUOR assay, we characterized human
      myoblasts expressing low or high levels of ALDH. We correlated high ALDH activity
      ex vivo to resistance to hydrogen peroxide (H(2) O(2) )-induced cytotoxic effect
      and in vivo to improved cell viability when human myoblasts were transplanted
      into host muscle of immune deficient scid mice. Therefore detection of ALDH
      activity, as a purification strategy, could allow non-toxic and efficient
      isolation of a fraction of human myoblasts resistant to cytotoxic damage.

PMID- 19840194
TI  - A systems biology perspective on sVEGFR1: its biological function, pathogenic
      role and therapeutic use.
AB  - Angiogenesis is the growth of new capillaries from pre-existent microvasculature.
      A wide range of pathological conditions, from atherosclerosis to cancer, can be
      attributed to either excessive or deficient angiogenesis. Central to the
      physiological regulation of angiogenesis is the vascular endothelial growth
      factor (VEGF) system--its ligands and receptors (VEGFRs) are thus prime molecular
      targets of pro-angiogenic and anti-angiogenic therapies. Of growing interest as a
      prognostic marker and therapeutic target in angiogenesis-dependent diseases is
      soluble VEGF receptor-1 (sVEGFR1, also known as sFlt-1)--a truncated version of
      the cell membrane-spanning VEGFR1. For instance, it is known that sVEGFR1 is
      involved in the endothelial dysfunction characterizing the pregnancy disorder of
      pre-eclampsia, and sVEGFR1's therapeutic potential as an anti-angiogenic agent is
      being evaluated in pre-clinical models of cancer. This mini review begins with an
      examination of the protein domain structure and biomolecular interactions of
      sVEGFR1 in relation to the full-length VEGFR1. A synopsis of known and inferred
      physiological and pathological roles of sVEGFR1 is then given, with emphasis on
      the utility of computational systems biology models in deciphering the molecular
      mechanisms by which sVEGFR1's purported biological functions occur. Finally, we
      present the need for a systems biology perspective in interpreting circulating
      VEGF and sVEGFR1 concentrations as surrogate markers of angiogenic status in
      angiogenesis-dependent diseases.

PMID- 19840195
TI  - Plasma gelsolin facilitates interaction between beta2 glycoprotein I and
      alpha5beta1 integrin.
AB  - Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence
      of antiphospholipid antibodies (aPL) that directly recognizes plasma beta(2)
      glycoprotein I (beta(2) GPI). Tissue factor (TF), the major initiator of the
      extrinsic coagulation system, is induced on monocytes by aPL in vitro, explaining
      in part the pathophysiology in APS. We previously reported that the mitogen
      activated protein kinase (MAPK) pathway plays an important role in aPL-induced TF
      expression on monocytes. In this study, we identified plasma gelsolin as a
      protein associated with beta(2) GPI by using immunoaffinity chromatography and
      mass spectrometric analysis. An in vivo binding assay showed that endogenous
      beta(2) GPI interacts with plasma gelsolin, which binds to integrin a(5) beta(1)
      through fibronectin. The tethering of beta(2) GPI to monoclonal anti-beta(2) GPI
      autoantibody on the cell surface was enhanced in the presence of plasma gelsolin.
      Immunoblot analysis demonstrated that p38 MAPK protein was phosphorylated by
      monoclonal anti-beta(2) GPI antibody treatment, and its phosphorylation was
      attenuated in the presence of anti-integrin a(5) beta(1) antibody. Furthermore,
      focal adhesion kinase, a downstream molecule of the fibronectin-integrin
      signalling pathway, was phosphorylated by anti-beta(2) GPI antibody treatment.
      These results indicate that molecules including gelsolin and integrin are
      involved in the anti-beta(2) GPI antibody-induced MAPK pathway on monocytes and
      that integrin is a possible therapeutic target to modify a prothrombotic state in
      patients with APS.

PMID- 19840196
TI  - FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth.
AB  - Four and a half LIM protein 1 (FHL1) belongs to the Lin-1, Isl-1 and Mec-3 (LIM)
      only protein family and plays important roles in muscle growth and
      carcinogenesis. However, the biological function of FHL1 remains largely unknown.
      Here, we show that FHL1 physically and functionally interacted with oestrogen
      receptors (ERs), which are involved in breast cancer development and progression.
      FHL1 bound specifically to the activation function-1 domain of ER. Physical
      interaction of FHL1 and ER is required for FHL1 repression of oestrogen
      responsive gene transcription. FHL1 affected recruitment of ER to an oestrogen
      responsive promoter and ER binding to an oestrogen-responsive element.
      Overexpression of FHL1 in breast cancer cells decreased expression of oestrogen
      responsive proteins, whereas knockdown of endogenous FHL1 with FHL1 small
      interfering RNA increased the expression of these proteins. Further analysis of
      46 breast cancer samples showed that FHL1 expression negatively associated with
      oestrogen-responsive gene expression in breast cancer cells. FHL1 inhibited
      anchorage-dependent and -independent breast cancer cell growth. These results
      suggest that FHL1 may play an important role in ER signalling as well as breast
      cancer cell growth regulation.

PMID- 19840197
TI  - Glomerular parietal epithelial cells of adult murine kidney undergo EMT to
      generate cells with traits of renal progenitors.
AB  - Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic
      phenotype in response to renal injury. However, the mechanism of de
      differentiation in GPECs and the underlying cellular processes are not fully
      understood. In the present study, we show that cultured GPECs of adult murine
      kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which
      express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and
      immunostaining of these clonogenic cells demonstrate that they exhibit metastable
      phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal
      (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of
      metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7,
      C-Ret) genes in these cells, indicating their bipotent progenitor status.
      Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression
      of renal progenitor markers reflecting the correlation between EMT and acquired
      stemness in these cells. Additional in vitro renal commitment assays confirmed
      their functional staminality. When injected into E13.5 kidney rudiments, the
      cells incorporated into the developing kidney primordia and co-culture with E13.5
      spinal cord resulted in branching and tubulogenesis in these cells. When
      implanted under renal capsule of unilaterally nephrectomized mice, these cells
      differentiated into immature glomeruli and vascular ducts. Our study demonstrates
      that EMT plays a major role in imparting plasticity to terminally differentiated
      GPECs by producing metastable cells with traits of kidney progenitors. The
      present study would improve our understanding on epithelial cell plasticity,
      furthering our knowledge of its role in renal repair and regeneration.

PMID- 19840198
TI  - Androgen receptor coactivator p44/Mep50 in breast cancer growth and invasion.
AB  - Hormones and their receptors play an important role in the development and
      progression of breast carcinoma. Although the primary focus has been on oestrogen
      and oestrogen receptor (ER), androgen, androgen receptor (AR) and its
      coactivator(s) have been implicated in tumorigenesis of breast carcinoma and
      warrant further investigation. AR coactivator p44/Mep50 is identified as a
      subunit of methylosome complex and lately characterized as an AR coactivator that
      enhances AR mediated transcription activity in a ligand dependent manner. In
      prostate cancer, p44 is expressed in the nucleus of benign epithelia and
      translocated into the cytoplasm in cancer cells. Furthermore, nuclear expression
      of p44 inhibits prostate cancer growth. In this report, we examined the
      expression and function of p44 in breast cancer. In addition to being an AR
      coactivator, p44 also functions as an ER coactivator. In contrast to findings in
      prostate cancer, the expression of p44 shows strong cytoplasmic expression in
      morphologically normal terminal ductal lobular units, while nuclear p44 is
      observed in both ductal carcinoma in situ and invasive carcinoma. Further,
      overexpression of nuclear-localized p44 stimulates proliferation and invasion in
      MCF7 breast cancer cells in the presence of oestrogen and the process is ERalpha
      dependent. These findings strongly suggest that p44 plays a role in mediating the
      effects of hormones during tumorigenesis in breast.

PMID- 19840199
TI  - An outbreak of Mycobacterium fortuitum cutaneous infection associated with
      mesotherapy.
AB  - OBJECTIVE: We describe an outbreak of Mycobacterium fortuitum cutaneous
      infections associated with mesotherapy in La Rioja, Spain. DESIGN: Descriptive
      epidemiology. SETTING: Private practice. PATIENTS OR OTHER PARTICIPANTS: Case
      subjects were customers of a single beauty salon who were treated with
      mesotherapy injections. INTERVENTION(S): Two skin biopsies were taken from each
      patient. RESULTS: Over the designated period, 138 women received mesotherapy. Of
      these women, 39, or 28.3%, developed lesions ultimately thought to be caused by
      Mycobacterium fortuitum infection. The number of lesions per patient varied from
      3 to 20 in the most severe case. Most of the lesions were indurated, erythematous
      or violaceous papules, some progressing to become fluctuant boils with
      suppuration, fistulization and scarring. The individual lesions varied in
      diameter from 0.5 to 6 cm. Two patients (5.1%) developed inguinal or axillary
      adenopathy. Two others presented with fever. One reported muscular pain. In 12 of
      the 39 cases, M. fortuitum was isolated from the wound cultures. The patients
      were all successfully treated with clarithromycin and levofloxacin. CONCLUSIONS:
      We identified a large outbreak of rapidly growing mycobacterial lesions among
      women who received mesotherapy injections in a single beauty salon.

PMID- 19840200
TI  - Clinicopathological characteristics of lichen planus pigmentosus and its response
      to tacrolimus ointment: an open label, non-randomized, prospective study.
AB  - BACKGROUND: Lichen planus pigmentosus (LPP) is an uncommon variant of lichen
      planus, for which no effective treatment is available. Objectives The aim of this
      study was to determine the clinical, epidemiological and histopathological
      characteristics of LPP patients in Kuwait. METHODS: Thirty-three LPP patients who
      attended the Dermatology outpatient clinics at Farwaniya Hospital, Kuwait from
      the year 2002 to 2008 were studied for clinical, epidemiological and
      histopathological findings. Thirteen of these patients were treated with topical
      tacrolimus 0.03%. Ointment applied topically twice daily for the duration varying
      from 6 to 12 weeks. RESULTS: Of the 33 patients, 21 were men and 12 were women.
      The duration of eruption ranged from 6 weeks to 3 years. The face and neck were
      the commonest sites, affecting 18 (54.5%) patients. The pattern of pigmentation
      was diffuse in 18 (54.54%) patients, reticular in seven (21.2%), blotchy in five
      (15.2%), linear in two (6.1%) and perifollicular in one (3%). Twenty patients had
      positive serology for hepatitis C virus (HCV), with significantly higher serum
      liver enzymes (ALT and AST). Of the 13 patients, who were treated with tacrolimus
      Ointment, seven (53.8%) showed appreciable lightening of the pigmentation after
      an average of 12 weeks. CONCLUSIONS: We conclude that HCV may be one of the
      factors associated with LPP, in those who have a tendency to develop LPP.
      However, this possible association should be interpreted carefully. In addition,
      tacrolimus ointment could have a beneficial role in the treatment of LPP.

PMID- 19840201
TI  - 'Matchstick' eyebrow hairs: a dermoscopic clue to the diagnosis of Netherton
      syndrome.

PMID- 19840202
TI  - Calcineurin inhibitors in the treatment of cutaneous infantile haemangiomas.

PMID- 19840203
TI  - Successful treatment of three cases of primary extramammary Paget's disease of
      the vulva with Imiquimod--proposal of a therapeutic schedule.
AB  - BACKGROUND/AIM: Extramammary Paget's disease (EMPD) is an intraepidermal
      adenocarcinoma of apocrine gland-bearing skin. Although surgery remains the
      mainstay of treatment, loss of tissue function and high recurrence rates have
      been reported. Recently, topical Imiquimod has been shown as a safe and effective
      treatment option for extramammary Paget's disease. METHODS: Three patients
      diagnosed of EMPD of the vulva were treated with a daily application of 5%
      Imiquimod cream for three weeks, followed by an every other day application for
      an additional three weeks. RESULTS: Complete clinical and histological remission
      of the disease was achieved in the three patients. Mild irritation and tenderness
      were observed as the only side effects. CONCLUSION: Based on our results, we
      consider that Imiquimod cream is a safe and effective therapeutic option for the
      treatment of vulvar EMPD. These promising results warrant further studies to
      determine the real efficacy and safety of Imiquimod 5% cream for the treatment of
      this uncommon disease.

PMID- 19840204
TI  - Clinal variation in post-winter male fertility retention; an adaptive
      overwintering strategy in Drosophila melanogaster.
AB  - In insects including Drosophila melanogaster, females can overwinter at the adult
      stage by adopting a shallow reproductive diapause, but almost nothing is known
      about male reproductive diapause. In this study, we test for the maintenance of
      fertility in overwintering males from the eastern Australian D. melanogaster
      cline. Males from southern temperate populations maintained in field cages in
      temperate Melbourne had a higher fertility in spring compared with males from
      tropical locations. Temperate males successfully inseminated more females, and
      there were also more offspring produced per inseminated female. The resulting
      linear post-winter fertility clines were unrelated to male body size. In
      contrast, there was no clinal variation for fertility in nonoverwintering males
      held in the laboratory. The cline in overwintering male fertility is likely to
      have evolved as an adaptive response to latitudinal climatic variation over the
      last 100 years.

PMID- 19840205
TI  - Basal metabolic rate and risk-taking behaviour in birds.
AB  - Basal metabolic rate (BMR) constitutes the minimal metabolic rate in the zone of
      thermo-neutrality, where heat production is not elevated for temperature
      regulation. BMR thus constitutes the minimum metabolic rate that is required for
      maintenance. Interspecific variation in BMR in birds is correlated with food
      habits, climate, habitat, flight activity, torpor, altitude, and migration,
      although the selective forces involved in the evolution of these presumed
      adaptations are not always obvious. I suggest that BMR constitutes the minimum
      level required for maintenance, and that variation in this minimum level reflects
      the fitness costs and benefits in terms of ability to respond to selective agents
      like predators, implying that an elevated level of BMR is a cost of wariness
      towards predators. This hypothesis predicts a positive relationship between BMR
      and measures of risk taking such as flight initiation distance (FID) of
      individuals approached by a potential predator. Consistent with this suggestion,
      I show in a comparative analysis of 76 bird species that species with higher BMR
      for their body mass have longer FID when approached by a potential predator. This
      effect was independent of potentially confounding variables and similarity among
      species due to common phylogenetic descent. These results imply that BMR is
      positively related to risk-taking behaviour, and that predation constitutes a
      neglected factor in the evolution of BMR.

PMID- 19840206
TI  - Walk and die: an unusual presentation of head injury.
AB  - We report three deaths in young adult males following closed blunt trauma to the
      head and face where the affected individuals were able to walk away from the
      incident, before subsequently collapsing and dying a short distance from the site
      of the assault. In each case, due to the rapidity of the posttrauma collapse, the
      pathologist was faced with a diagnostic difficulty at autopsy; the external
      examination revealed multiple injuries to the head and face, but internal
      examinations showed limited findings with no structural explanation for the
      death. We discuss possible mechanisms that could account for this scenario, the
      implications of alcohol consumption with a concussive head injury, and parallels
      that can be drawn with the so-called "talk and die,""talk and deteriorate," and
      "second impact syndrome." Finally, the possible role of so-called "postexercise
      peril" is discussed in relation to these deaths.

PMID- 19840207
TI  - Fast multiplexed polymerase chain reaction for conventional and microfluidic
      short tandem repeat analysis.
AB  - The time required for short tandem repeat (STR) amplification is determined by
      the temperature ramp rates of the thermal cycler, the components of the reaction
      mix, and the properties of the reaction vessel. Multiplex amplifications in
      microfluidic biochip-based and conventional tube-based thermal cyclers have been
      demonstrated in 17.3 and 19 min, respectively. Optimized 28-cycle amplification
      protocols generated alleles with signal strengths above calling thresholds,
      heterozygous peak height ratios of greater than 0.65, and incomplete nontemplate
      nucleotide addition and stutter of less than 15%. Full CODIS-compatible profiles
      were generated using the Profiler Plus ID, COfiler and Identifiler primer sets.
      PCR performance over a wide range of DNA template levels from 0.006 to 4 ng was
      characterized by separation and detection on a microfluidic electrophoresis
      system, Genebench-FX. The fast multiplex PCR approach has the potential to reduce
      process time and cost for STR analysis and enables development of a fully
      integrated microfluidic forensic DNA analysis system.

PMID- 19840208
TI  - Integrating DSM-IV factors to predict violence in high-risk psychiatric patients.
AB  - This study incorporated Axis-II and Axis-IV factors in DSM-IV to test the
      relationship between predicted risk for violence assessed in the psychiatric
      emergency room and actual violence during hospitalization. Psychiatric nurses
      lack an objective instrument to use during the acute psychiatric assessment. The
      retrospective study comprised consecutive psychiatric admissions (n = 161) in one
      tertiary veterans' hospital. Statistical testing for the predictive power of risk
      factors, relationships between variables, and violent events included
      nonparametric tests, factor analysis, and logistic regression. Of the 32 patients
      who committed violence during hospitalization, 12 had committed violence in the
      psychiatric emergency room. Statistical significance was shown for violent
      incidents and dementia, court-ordered admission, mood disorder, and for three or
      more risk factors. The 13-item Risk of Violence Assessment (ROVA) scale suggests
      validity and sensitivity for rating DSM-IV factors and psychosocial stressors to
      predict risk for violence during hospitalization. Replication studies are
      recommended to strengthen validity of the ROVA scale.

PMID- 19840210
TI  - Abstracts of the Royal Australian and New Zealand College of
      Radiologists/Australian Institute of Radiography/Faculty of Radiation
      Oncology/Australasian College of Physical Scientists & Engineers in Medicine
      Combined Scientific Meeting, 22-25 October, 2009. Brisbane, Queensland,
      Australia.

PMID- 19840216
TI  - Hippocampal seizures alter the expression of the pannexin and connexin
      transcriptome.
AB  - Some forms of seizure activity can be stopped by gap junctional (GJ) blockade.
      Here, we found that GJ blockers attenuate hippocampal seizure activity induced by
      a novel seizuregenic protocol using Co(2+). We hypothesized that this activity
      may occur because of the altered expression of connexin (Cx) and/or pannexin
      (Panx) mRNAs and protein. We found a 1.5-, 1.4-, and 2-fold increase in Panx1,
      Panx2, and Cx43 mRNAs, respectively. Significant post-translational modifications
      of the proteins Cx43 and Panx1 were also observed after the Co(2+) treatment. No
      changes were observed in the presence of tetrodotoxin, indicating that seizure
      activity is required for these alterations in expression, rather than the Co(2+)
      treatment itself. Further analysis of the QPCR data showed that the Cx and Panx
      transcriptome becomes remarkably re-organized. Pannexin (Panxs 1 and 2) and glial
      connexin mRNA became highly correlated to one another; suggesting that these
      genes formed a transcriptomic network of coordinated gene expression, perhaps
      facilitating seizure induction. These data show that seizure activity up
      regulates the expression of both glial and neuronal GJ mRNAs and protein while
      inducing a high degree of coordinate expression of the GJ transcriptome.

PMID- 19840215
TI  - Granulocyte-macrophage colony-stimulating factor antibody suppresses microglial
      activity: implications for anti-inflammatory effects in Alzheimer's disease and
      multiple sclerosis.
AB  - The objective of our study was to determine granulocyte-macrophage colony
      stimulating factor (GM-CSF) activity in the brain following GM-CSF induction. We
      injected recombinant mouse GM-CSF into the brains of 8-month-old C57BL6 mice via
      intracerebroventricular injections and studied the activities of microglia,
      astrocytes, and neurons. We also sought to determine whether an anti-GM-CSF
      antibody could suppress endogenous microglial activity in the C57BL6 mice and
      could also suppress microglial activity induced by the recombinant mouse GM-CSF
      in another group of C57BL6 mice. Using quantitative real-time RT-PCR, we assessed
      microglial, astrocytic, and neuronal activity by measuring mRNA expression of pro
      inflammatory cytokines, GFAP, and the neuronal marker NeuN in the cerebral cortex
      tissues from C57BL6 mice. We performed immunoblotting and immunohistochemistry of
      activated microglia in different regions of the brains from control (phosphate
      buffered saline-injected C57BL6 mice) and experimental mice (recombinant GM-CSF
      injected C57BL6 mice, GM-CSF antibody-injected C57BL6 mice, and recombinant mouse
      GM-CSF plus anti-GM-CSF antibody-injected C57BL6 mice). We found increased mRNA
      expression of CD40 (9.75-fold), tumor necrosis factor-alpha (2.1-fold), CD45
      (1.73-fold), and CD11c (1.70-fold) in the cerebral cortex of C57BL6 mice that
      were induced with recombinant GM-CSF, compared with control mice. Further, the
      anti-GM-CSF antibody suppressed microglia in mice that were induced with
      recombinant GM-CSF. Our immunoblotting and immunohistochemistry findings of GM
      CSF-associated cytokines in C57BL6 mice induced with recombinant GM-CSF, in
      C57BL6 mice injected with the anti-GM-CSF antibody, and in C57BL6 mice injected
      with recombinant mouse GM-CSF plus anti-GM-CSF antibody concurred with our real
      time RT-PCR findings. These findings suggest that GM-CSF is critical for
      microglial activation and that anti-GM-CSF antibody suppresses microglial
      activity in the CNS. The findings from this study may have implications for anti
      inflammatory effects of Alzheimer's disease and experimental autoimmune
      encephalomyelitis mice (a multiple sclerosis mouse model).

PMID- 19840217
TI  - The loop between beta-strands beta 2 and beta 3 and its interaction with the N
      terminal alpha-helix is essential for biogenesis of alpha 7 nicotinic receptors.
AB  - Recently, we have shown that the alpha-helix present at the N-termini of alpha7
      nicotinic acetylcholine receptors plays a crucial role in their biogenesis.
      Structural data suggest that this helix interacts with the loop linking beta
      strands beta2 and beta3 (loop 3). We studied the role of this loop as well as its
      interaction with the helix in membrane receptor expression. Residues from Asp62
      to Val75 in loop 3 were mutated. Mutations of conserved amino acids, such as
      Asp62, Leu65 and Trp67 abolished membrane receptor expression in Xenopus oocytes.
      Others mutations, at residues Asn68, Ala69, Ser70, Tyr72, Gly74, and Val 75 were
      less harmful although still produced significant expression decreases. Steady
      state levels of wild-type and mutant alpha7 receptors (L65A, W67A, and Y72A) were
      similar but the formation of pentameric receptors was impaired in the latter
      (W67A). Mutation of critical residues in subunits of heteromeric nicotinic
      acetylcholine receptors (alpha3beta4) also abolished their membrane expression.
      Complementarity between the helix and loop 3 was evidenced by studying the
      expression of chimeric alpha7 receptors in which these domains were substituted
      by homologous sequences from other subunits. We conclude that loop 3 and its
      docking to the alpha-helix is an important requirement for receptor assembly.

PMID- 19840218
TI  - Protein aggregation in neurons following OGD: a role for Na+ and Ca2+ ionic
      dysregulation.
AB  - In this study, we investigated whether disruption of Na(+) and Ca(2+) homeostasis
      via activation of Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) and reversal
      of Na(+)/Ca(2+) exchange (NCX(rev)) affects protein aggregation and degradation
      following oxygen-glucose deprivation (OGD). Cultured cortical neurons were
      subjected to 2 h OGD and 1-24 h reoxygenation (REOX). Redistribution of ubiquitin
      and formation of ubiquitin-conjugated protein aggregates occurred in neurons as
      early as 2 h REOX. The protein aggregation progressed further by 8 h REOX. There
      was no significant recovery at 24 h REOX. Moreover, the proteasome activity in
      neurons was inhibited by 80-90% during 2-8 h REOX and recovered partially at 24 h
      REOX. Interestingly, pharmacological inhibition or genetic ablation of NKCC1
      activity significantly decreased accumulation of ubiquitin-conjugated protein
      aggregates and improved proteasome activity. A similar protective effect was
      obtained by blocking NCX(rev) activity. Inhibition of NKCC1 activity also
      preserved intracellular ATP and Na(+) homeostasis during 0-24 h REOX. In a
      positive control study, disruption of endoplasmic reticulum Ca(2+) with
      thapsigargin triggered redistribution of free ubiquitin and protein aggregation.
      We conclude that overstimulation of NKCC1 and NCX(rev) following OGD/REOX
      partially contributes to protein aggregation and proteasome dysfunction as a
      result of ionic dysregulation.

PMID- 19840219
TI  - Regulation of increased glutamatergic input to spinal dorsal horn neurons by
      mGluR5 in diabetic neuropathic pain.
AB  - Diabetic neuropathic pain is associated with increased glutamatergic input in the
      spinal dorsal horn. Group I metabotropic glutamate receptors (mGluRs) are
      involved in the control of neuronal excitability, but their role in the
      regulation of synaptic transmission in diabetic neuropathy remains poorly
      understood. Here we studied the role of spinal mGluR5 and mGluR1 in controlling
      glutamatergic input in a rat model of painful diabetic neuropathy induced by
      streptozotocin. Whole-cell patch-clamp recordings of lamina II neurons were
      performed in spinal cord slices. The amplitude of excitatory post-synaptic
      currents (EPSCs) evoked from the dorsal root and the frequency of spontaneous
      EPSCs (sEPSCs) were significantly higher in diabetic than in control rats. The
      mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) inhibited evoked
      EPSCs and sEPSCs more in diabetic than in control rats. Also, the percentage of
      neurons in which sEPSCs and evoked EPSCs were affected by MPEP or the group I
      mGluR agonist was significantly higher in diabetic than in control rats. However,
      blocking mGluR1 had no significant effect on evoked EPSCs and sEPSCs in either
      groups. The mGluR5 protein level in the dorsal root ganglion, but not in the
      dorsal spinal cord, was significantly increased in diabetic rats compared with
      that in control rats. Furthermore, intrathecal administration of MPEP
      significantly increased the nociceptive pressure threshold only in diabetic rats.
      These findings suggest that increased mGluR5 expression on primary afferent
      neurons contributes to increased glutamatergic input to spinal dorsal horn
      neurons and nociceptive transmission in diabetic neuropathic pain.

PMID- 19840221
TI  - N-acetylcysteine inhibits hyperglycemia-induced oxidative stress and apoptosis
      markers in diabetic neuropathy.
AB  - Several studies have indicated the involvement of oxidative stress in the
      development of diabetic neuropathy. In the present study, we have targeted
      oxidative stress mediated nerve damage in diabetic neuropathy using N-acetyl-l
      cysteine (NAC), a potent antioxidant. After 8 weeks, streptozotocin-induced
      diabetic rats developed neuropathy which was evident from decreased tail-flick
      latency (thermal hyperalgesia). This was accompanied by decreased motor
      coordination as assessed by performance on rota-rod treadmill. Na(+) K(+) ATPase,
      a biochemical marker of development of diabetic neuropathy, was significantly
      inhibited in sciatic nerve of diabetic animals. NAC treatment at a daily dose
      between 1.4 and 1.5 g/kg body weight to diabetic animals for 7 weeks in drinking
      water ameliorated hyperalgesia, improved motor coordination and reversed
      reduction in Na(+) K(+) ATPase activity. There was an increase in lipid
      peroxidation in sciatic nerve of diabetic animals along with decrease in
      phospholipid levels, while NAC treatment attenuated lipid peroxidation and
      restored phospholipids to control levels. This was associated with decrease in
      glutathione and protein thiols. The activities of antioxidant enzymes; superoxide
      dismutase, catalase, glutathione reductase, glutathione peroxidase and
      glutathione-S-transferase were reduced in sciatic nerve of diabetic animals.
      Cytochrome c release and active caspase 3 were markedly increased in nerve from
      diabetic animals suggesting activation of apoptotic pathway. NAC treatment
      significantly ameliorated decrease in antioxidant defense and prevented
      cytochrome c release and caspase 3 activation. Electron microscopy revealed
      demyelination, Wallerian degeneration and onion-bulb formation in sciatic nerve
      of diabetic rats. NAC on the other hand was able to reverse structural deficits
      observed in sciatic nerve of diabetic rats. Our results clearly demonstrate
      protective effect of NAC is mediated through attenuation of oxidative stress and
      apoptosis, and suggest therapeutic potential of NAC in attenuation of diabetic
      neuropathy.

PMID- 19840220
TI  - CaMKII associates with CaV1.2 L-type calcium channels via selected beta subunits
      to enhance regulatory phosphorylation.
AB  - Calcium/calmodulin-dependent kinase II (CaMKII) facilitates L-type calcium
      channel (LTCC) activity physiologically, but may exacerbate LTCC-dependent
      pathophysiology. We previously showed that CaMKII forms stable complexes with
      voltage-gated calcium channel (VGCC) beta(1b) or beta(2a) subunits, but not with
      the beta(3) or beta(4) subunits (Grueter et al. 2008). CaMKII-dependent
      facilitation of Ca(V)1.2 LTCCs requires Thr498 phosphorylation in the beta(2a)
      subunit (Grueter et al. 2006), but the relationship of this modulation to CaMKII
      interactions with LTCC subunits is unknown. Here we show that CaMKII co
      immunoprecipitates with forebrain LTCCs that contain Ca(V)1.2alpha(1) and beta(1)
      or beta(2) subunits, but is not detected in LTCC complexes containing beta(4)
      subunits. CaMKIIalpha can be specifically tethered to the I/II linker of Ca(V)1.2
      alpha(1) subunits in vitro by the beta(1b) or beta(2a) subunits. Efficient
      targeting of CaMKIIalpha to the full-length Ca(V)1.2alpha(1) subunit in
      transfected HEK293 cells requires CaMKII binding to the beta(2a) subunit.
      Moreover, disruption of CaMKII binding substantially reduced phosphorylation of
      beta(2a) at Thr498 within the LTCC complex, without altering overall
      phosphorylation of Ca(V)1.2alpha(1) and beta subunits. These findings demonstrate
      a biochemical mechanism underlying LTCC facilitation by CaMKII.

PMID- 19840222
TI  - Early undernutrition increases glycogen content and reduces the activated forms
      of GSK3, AMPK, p38 MAPK, and JNK in the cerebral cortex of suckling rats.
AB  - Exposure to maternal undernutrition during development increases the risk for
      neurological and cognitive defects. However, little is known about the underlying
      mechanisms involved. Peripheral responses to insulin are increased following food
      restriction, thus the possibility arises that brain insulin actions are affected
      by undernutrition, causing damages to the higher cerebral functions. In this
      study, we examined the effects of early undernutriton on molecular targets of
      insulin actions such as glucose transporters, glycogen, glycogen synthase kinase
      3 (GSK3) and mitogen-activated protein kinases, as well as proteins involved in
      apoptosis in the cortex from 10-day-old rats. We show that undernutrition results
      in an enhanced glycogen content which is confined to astrocytes, according to our
      histochemical approaches. Cortical phospho-GSK3 is also increased. In addition to
      glycogen synthesis, GSK3 regulates crucial cellular processes. Therefore, its
      elevated degree of phosphorylation may have an impact on these processes and,
      consequently, on the cortical development. Phospho-p38 and both total JNK and
      phospho-JNK, which regulate apoptosis, are reduced following undernutrition.
      However, cleaved caspase 3 is not altered, which suggests that this condition
      does not induce extensive modifications to the cortical apoptosis. Thus, our
      results indicate that undernutrition gives rise to molecular alterations that may
      have repercussions on cerebral cortex development and functions.

PMID- 19840224
TI  - Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating
      MAP1B and paxillin.
AB  - Nerve growth factor (NGF) promotes neurite outgrowth through regulating
      cytoskeletal organization and cell adhesion. These activities are modulated by
      protein phosphorylation. Nemo-like kinase (NLK) is an evolutionarily conserved
      MAP kinase-like kinase that phosphorylates several transcription factors.
      Although NLK is known to be expressed at relatively high levels in the nervous
      system, its function is not well understood. We found that NGF promotes the
      translocation of NLK to PC12 cells' leading edges, and triggers NLK kinase
      activity in them. Activated NLK directly phosphorylates microtubule-associated
      protein-1B (MAP1B) and the focal adhesion adaptor protein, paxillin. Knockdown of
      NLK attenuates the phosphorylation of both paxillin and MAP1B and inhibits both
      the NGF-induced re-distribution of F-actin and neurite outgrowth. We also
      discovered that NLK is a LiCl-sensitive kinase. LiCl is known to block NGF
      induced neurite outgrowth and the phosphorylation of MAP1B and paxillin in PC12
      cells. Therefore, the effects of LiCl are mediated in part by blocking NLK
      activity. These results suggest that NLK controls the dynamics of the
      cytoskeleton downstream of NGF signaling.

PMID- 19840223
TI  - Increased intranuclear matrix metalloproteinase activity in neurons interferes
      with oxidative DNA repair in focal cerebral ischemia.
AB  - Increased matrix metalloproteinase (MMP) activity is implicated in proteolysis of
      extracellular matrix in ischemic stroke. We recently observed intranuclear MMP
      activity in ischemic brain neurons at early reperfusion, suggesting a possible
      role in nuclear matrix proteolysis. Nuclear proteins, poly-ADP-ribose polymerase
      1 (PARP-1) and X-ray cross-complementary factor 1 (XRCC1), as well as DNA repair
      enzymes, are important in DNA fragmentation and cell apoptosis. We hypothesized
      that intranuclear MMP activity facilitates oxidative injury in neurons during
      early ischemic insult by cleaving PARP-1 and XRCC1, interfering with DNA repair.
      We induced a 90-min middle cerebral artery occlusion in rats. Increase activity
      of MMP-2 and -9, detected in the ischemic neuronal nuclei at 3 h, was associated
      with DNA fragmentation at 24 and 48 h reperfusion. The intranuclear MMPs cleaved
      PARP-1. Treatment of the rats with a broad-spectrum MMP inhibitor, BB1101,
      significantly attenuated ischemia-induced PARP-1 cleavage, increasing its
      activity. Degradation of XRCC1 caused by ischemic insult in rat brain was also
      significantly attenuated by BB1101. We found elevation of oxidized DNA,
      apurinic/apyrimidinic sites, and 8-hydroxy-2'-deoxyguanosine, in ischemic brain
      cells at 3 h reperfusion. BB1101 markedly attenuated the early increase of
      oxidized DNA. Using tissue from stroke patients, we found increased intranuclear
      MMP expression. Our data suggest that intranuclear MMP activity cleaves PARP-1
      and XRCC1, interfering with oxidative DNA repair. This novel role for MMPs could
      contribute to neuronal apoptosis in ischemic injuries.

PMID- 19840225
TI  - Effects of post materials and length on the stress distribution of endodontically
      treated maxillary central incisors: a 3D finite element analysis.
AB  - Traditionally, using a long post can cause progressive removal of the root
      structure, complicate the ability to re-treat the tooth if necessary and make it
      difficult to apply an adhesive bonding agent into the root canal. It is unclear
      if a shorter post length can be applied when a light translucent glass fibre post
      and adhesive resin cement are used. The aim of this study was to evaluate the
      biomechanical performance of endodontically treated teeth restored with three
      post materials, glass-fibre, stainless steel and cast-nickel chromium posts and
      cores of different lengths of 7, 10 and 13 mm. A 3D finite element analysis model
      of the maxillary central incisor was constructed. An occlusal load of 300 N was
      applied to a node at the palatal surface of the crown at 45 degrees to the long
      axis of the tooth. von Mises stress analyses were carried out in three regions.
      Simulated data were collected for plotting various pattern graphics and
      conducting statistical tests. The pattern graphics showed that when the post
      length changed from 13 to 7 mm, the stress patterns were even and flat in all
      fibre-post groups, while the stress patterns of the metal-post groups showed an M
      shaped peak and trough. Statistical tests showed that the shorter fibre post was
      superior to the longer metal post in some situations. Within the limitations of
      this study, it was concluded that when a metal post is used, the post should be
      as long as possible, while the biomechanical performance of a glass-fibre post
      combined with a composite resin core was less sensitive to post length.

PMID- 19840227
TI  - What role can school health providers play in health care reform?

PMID- 19840228
TI  - Social and ecological structures supporting adolescent connectedness to school: a
      theoretical model.
AB  - BACKGROUND: Adolescence is a time of great change. For most young people, this is
      a healthy and happy experience; however, for some it is characterized by many
      health, social, and academic challenges. A student's feeling of connectedness to
      school helps meet these challenges. Little is known, however, about the school
      characteristics that promote this connection and, more importantly, how this
      connection occurs. This article reviews the connectedness literature and
      integrates health promotion, adolescent development, and ecological frameworks to
      describe how a school context fosters this connection. METHOD: A systematic
      search and review process was used to retrieve scholarly articles pertaining to
      the research topic. RESULTS: Each retrieved article was summarized, and a
      subsequent model was developed to define a school ecology and describe how this
      ecology influences a student's need to feel connected to school and the positive
      influence this connection has on adolescent health and well-being. CONCLUSIONS:
      Integrating developmental, ecological, and health promotion intervention theories
      and frameworks assists in the identification of interpersonal and organizational
      aspects of a school environment, which satisfy an individual's needs to feel
      autonomous, competent, and connected, and to improve health and well-being
      outcomes for adolescents.

PMID- 19840229
TI  - The impact of school socioeconomic status on student lunch consumption after
      implementation of the Texas Public School Nutrition Policy.
AB  - BACKGROUND: This study compares the impact of the Texas Public School Nutrition
      Policy on lunch consumption of low- and middle-income students in sixth through
      eighth grades. METHODS: Students in 1 middle socioeconomic status (SES) and 1 low
      SES school completed lunch food records before (2001/2002) and after (2005/2006)
      implementation of the Texas policy. Students recorded amount and source of
      foods/beverages consumed. Two-way analyses of variance with year and school SES
      as factors were performed to compare consumption by school SES before and after
      implementation of the Texas policy. RESULTS: Regardless of year, the low SES
      group consumed less fat, sweetened beverages, and candy and more vitamin C and
      calcium than the middle SES group. There were more significant improvements in
      dietary patterns for the middle SES school students post-policy, particularly
      from the National School Lunch Program (NSLP) meal. The middle SES school
      students reported significantly higher percentages of less healthy items from
      home post-policy. CONCLUSIONS: Overall, low SES school students consumed more
      healthy lunches at school compared with middle SES school students, and the Texas
      policy improved middle SES school student dietary intakes. Whether the dietary
      behaviors in school influence dietary intake for the entire day is unknown.

PMID- 19840230
TI  - Gender differences in food preferences of school-aged children and adolescents.
AB  - BACKGROUND: Schools have the opportunity, through the National School Lunch
      Program and Local School Wellness Policies, to have a significant impact on
      healthy eating behaviors. An understanding of children's and adolescents' food
      preferences in relation to gender and age will facilitate the successful creation
      of both healthy and financially viable school menus. The purpose of this study
      was to identify food preferences with respect to gender of school-age children
      and adolescents in an Ohio school district. METHODS: A survey was administered to
      1818 3rd- to 12th-grade students in 1 rural northeast Ohio school district.
      Students filled out an anonymous questionnaire about their preferences for 80
      different foods using a 5-point rating scale. The student data were grouped
      according to school level attended: elementary (3rd-6th), middle (7th-8th), and
      high school (9th-12th). An exploratory factor analysis identified entree and side
      dish factors. Cronbach's alpha was used to measure each factor's internal
      reliability. Differences in mean scores by gender and grade for each of the
      entree and side dish factors by gender and grade were identified using analysis
      of variance (ANOVA). RESULTS: Boys preferred the meat, fish, and poultry foods
      over girls; girls preferred fruits and vegetables over boys (p < .05).
      Furthermore, gender differences in preferences were also demonstrated with
      respect to school level. CONCLUSIONS: Food preferences differed between genders
      and these gender differences varied among elementary, middle, and high school
      students. Gender differences should be considered when providing food choices to
      boys and girls at all ages.

PMID- 19840231
TI  - The impact of nutrition standards on competitive food offerings and purchasing
      behaviors of high school students.
AB  - BACKGROUND: With adolescent obesity rates on the rise, the school food
      environment is receiving closer scrutiny. This study looks at the effects of
      nutrient standards as part of a wellness policy that was implemented in 3 public
      high schools in 1 county, by analyzing the nutritional value of competitive food
      offerings and purchases before and after the development of the standards.
      METHODS: All food offerings and purchases were labeled based on their nutritional
      density using a stoplight approach of green, yellow, and red colors for the pre-
      and post- period. The stoplight approach to ranking foods is on a continuum of
      nutrient density, with green foods being the healthiest choices and red foods
      offering minimal nutrient density. RESULTS: Results showed that after the
      implementation of the standards, red foods made up 30% of offerings, down from
      48% of offerings prior to the existence of the guidelines. The proportion of red
      food purchases also decreased, from 83% to 47%. Additionally, yellow food
      offerings increased from 18% to 48% and purchases increased from 6% to 34%.
      CONCLUSION: Results indicate that the nutrient standards as part of the wellness
      policy contributed to a positive shift in the nutritional value of competitive
      food purchases and offerings.

PMID- 19840232
TI  - Clustering of Internet risk behaviors in a middle school student population.
AB  - BACKGROUND: Internet safety is a growing public concern especially among adults
      and youth who live in an "instant messaging" world of technological
      communication. To better understand how early adolescents are using the Internet,
      a study was undertaken to more clearly identify the online general use, safety
      knowledge, and risk behaviors of middle school students. METHODS: This
      exploratory study adapted from Finkelhor et al's (2000) Youth Internet Safety
      Survey to identify the usage and characteristics of online youth, solicitation of
      youth, and searching for pornography or delinquent behaviors. The 404 students
      who were recruited from public and parochial schools consisted of both boys and
      girls with a mean age 12 years. RESULTS: These students reported the beginnings
      of high-risk Internet behavior, specifically, giving out personal information,
      using the Internet to harass or embarrass another person, and for a small number
      of students, chatting with strangers and starting relationships. The students who
      posted their picture online were more likely to have sent their picture to
      someone, made rude comments to others, played online jokes, harassed or
      embarrassed someone, and sought out pornographic sites. CONCLUSIONS: Findings
      suggest that middle school students who are early adolescents are beginning risky
      behaviors on the Internet. Risk-taking behavior is not unique to adolescents, but
      the consequences can be detrimental to their development. Educators, clinicians,
      health care providers, and other professionals need to be informed of Internet
      behaviors in order to assess for children at risk, to make referrals, intervene,
      and to educate parents.

PMID- 19840233
TI  - Development and reliability of items measuring the nonmedical use of prescription
      drugs for the Youth Risk Behavior Survey: results from an initial pilot test.
AB  - BACKGROUND: The purpose of this study was to develop and test the reliability of
      self-report survey items designed to monitor the nonmedical use of prescription
      drugs among adolescents. METHODS: Eighteen nonmedical prescription drug items
      designed to be congruent with the substance abuse items in the US Centers for
      Disease Control and Prevention's (CDC's) Youth Risk Behavior Survey were
      constructed, reviewed by a panel of experts, and then examined to assess
      reliability using a test-retest survey design. RESULTS: Simple kappa (kappa)
      coefficients for 14 of the 18 items demonstrated "substantial" or "almost
      perfect" reliability. Three items had coefficients within the "fair" or
      "moderate" ranges and 1 item fell within in the "poor" range. Of the 10 items for
      which weighted kappa coefficients were calculated, 6 items fell within the
      "almost perfect" or "substantial" ranges. Three fell within the "moderate" range
      and 1 fell within the "poor" range. CONCLUSIONS: Based on the expert panel review
      and the findings from our study, most of the 18 items developed to measure
      nonmedical use of prescription drugs among adolescents appear valid and reliable.
      The nonmedical use of prescription drugs ranks fourth among the most abused class
      of drugs by adolescents after alcohol, tobacco, and marijuana, respectively. The
      CDC should consider expanding the surveillance of these specific health-risk
      behaviors that are assuming new importance by including the items described in
      this article in future national surveys.

PMID- 19840235
TI  - Oestradiol and insulin-like growth factor-1 reduce cell loss after global
      ischaemia in middle-aged female rats.
AB  - Whereas the ability of oestradiol and insulin-like growth factor (IGF)-1 to
      afford neuroprotection against ischaemia-induced neuronal death in young female
      and male rodents is well established, the impact of IGF-1 in middle-aged animals
      is largely unknown. The present study assessed the efficacy of oestradiol and IGF
      1 with respect to reducing neuronal death after transient global ischaemia in
      middle-aged female rats after 8 weeks of hormone withdrawal. Rats were
      ovariohysterectomised and implanted 8 weeks later with an osmotic mini-pump
      delivering IGF-1 or saline into the lateral ventricle. Some rats also received
      physiological levels of oestradiol by subcutaneous pellet. Two weeks later, rats
      were subjected to global ischaemia or sham operation. Surviving hippocampal CA1
      neurones were quantified. Ischaemia produced massive CA1 cell death compared to
      sham-operated animals, which was evident at 14 days. Significantly more neurones
      survived in animals treated with either oestradiol or IGF-1, but simultaneous
      treatment produced no additive effect. IGF-1, an endogenous growth factor, may be
      a clinically useful therapy in preventing human brain injury, with
      neuroprotective equivalence to oestradiol but without the harmful side-effects.

PMID- 19840236
TI  - Kisspeptin/Gpr54-independent gonadotrophin-releasing hormone activity in Kiss1
      and Gpr54 mutant mice.
AB  - The kisspeptin/Gpr54 signalling pathway plays a critical role in reproduction by
      stimulating the secretion of gonadotrophin-releasing hormone (GnRH), yet mice
      carrying mutations in Kiss1 (which encodes kisspeptin) or Gpr54 exhibit partial
      sexual maturation. For example, a proportion of female Kiss1(-/-) and Gpr54(-/-)
      mice exhibit vaginal oestrus, and some male Kiss1(-/-) and Gpr54(-/-) mice
      exhibit spermatogenesis. To characterise this partial sexual maturation, we
      examined the vaginal cytology of female Kiss1(-/-) and Gpr54(-/-) mice over time.
      Almost all mutant mice eventually enter oestrus, and then spontaneously
      transition from oestrus to dioestrus and back to oestrus again. These transitions
      are not associated with ovulation, and the frequency of these transitions
      increases with age. The oestrus exhibited by female Kiss1(-/-) and Gpr54(-/-)
      mice was disrupted by the administration of the competitive GnRH antagonist
      acyline, which also resulted in lower uterine weights and, in Kiss1(-/-) mice,
      lower serum follicle-stimulating hormone (FSH) and luteinising hormone (LH)
      concentrations. Similarly, male Kiss1(-/-) and Gpr54(-/-) mice treated with
      acyline had smaller testicular sizes and an absence of mature sperm. In addition
      to examining intact Kiss1(-/-) and Gpr54(-/-) mice, we also assessed the effects
      of acyline on gonadotrophin concentrations in gonadectomised mice. Gonadectomy
      resulted in a significant increase in serum FSH concentrations in male Gpr54(-/-)
      and Kiss1(-/-) mice. Acyline administration to gonadectomised Kiss1(-/-) and
      Gpr54(-/-) male mice lowered serum FSH and LH concentrations significantly. By
      contrast to males, gonadectomy did not result in significant gonadotrophin
      changes in female Kiss1(-/-) and Gpr54(-/-) mice, but acyline administration was
      followed by a decrease in LH concentrations. These results demonstrate that,
      although kisspeptin signalling is critical for the high levels of GnRH activity
      required for normal sexual maturation and for ovulation, Kiss1(-/-) and Gpr54(-/
      ) mice retain some degree of GnRH activity. This GnRH activity is sufficient to
      produce significant effects on vaginal cytology and uterine weights in female
      mice and on spermatogenesis and testicular weights in male mice.

PMID- 19840237
TI  - Genistein induces phosphorylation of cAMP response element-binding protein in
      neonatal hypothalamus in vivo.
AB  - We investigated the effect of the phytoestrogen, genistein and 17beta-oestradiol
      on cAMP response element-binding protein (CREB) phosphorylation in the neonatal
      female rat hypothalamus in vivo using western blot analysis and
      immunohistochemistry. Although CREB expression was insensitive to the compounds
      we tested, administration of genistein and 17beta-oestradiol induced rapid CREB
      phosphorylation (< 15 min) in the hypothalamus and its level remained elevated at
      4 h. Quantitative immunohistochemical analysis showed that genistein and 17beta
      oestradiol had no effect on CREB phosphorylation in the magnocellular subdivision
      of paraventricular nucleus. By contrast, genistein induced a dose-dependent
      increase in CREB phosphorylation in the medial preoptic area (mPOA) and
      anteroventral periventricular nucleus (AVPV). Administration of 17beta-oestradiol
      also caused a rapid, dose-dependent increase in CREB phosphorylation in the
      hypothalamus, mPOA and AVPV. These results demonstrate that genistein induces
      oestrogen-like rapid action on CREB phosphorylation in the neonatal central
      nervous system in vivo.

PMID- 19840238
TI  - Photic and nonphotic seasonal cues differentially engage hypothalamic kisspeptin
      and RFamide-related peptide mRNA expression in Siberian hamsters.
AB  - Seasonally breeding animals use a combination of photic (i.e. day length) and
      nonphotic (e.g. food availability, temperature) cues to regulate their
      reproduction. How these environmental cues are integrated is not understood. To
      assess the potential role of two candidate neuropeptides, kisspeptin and RFamide
      related peptide-3 (RFRP), we monitored regional changes in their gene expression
      in a seasonally breeding mammal exposed to moderate changes in photoperiod and
      food availability. Adult male Siberian hamsters (Phodopus sungorus) were housed
      under a long (16 h light/day; 16 L) or intermediate (13.5 L) photoperiod and fed
      ad lib. or a progressive food restriction schedule (FR; reduced to 80% of ad
      lib.) for 11 weeks. Gonadal regression occurred only in FR hamsters housed under
      13.5 L. Immunohistochemistry was used to identify diencephalic populations of
      kisspeptin- and RFRP-immunoreactive cells, and quantitative PCR was used to
      measure gene expression in adjacent coronal brain sections. Photoperiod, but not
      food availability, altered RFRP mRNA expression in the dorsomedial sections,
      whereas food availability but not photoperiod altered Kiss1 expression in the
      arcuate sections; intermediate photoperiods elevated RFRP expression, and food
      restriction suppressed Kiss1 expression. Regional- and neuropeptide-specific
      activity of RFamides may provide a mechanism for integration of multi-modal
      environmental information in the seasonal control of reproduction.

PMID- 19840239
TI  - Leptin: back and forward.
AB  - The discovery of leptin resulted in a gear change in obesity research. Exploiting
      its therapeutic potential has proved to be a long game, although encouraging
      progress is now being made with leptin monotherapy in conditions of relative
      deficiency, and with combination therapy against common obesity. Leptin's role in
      early brain development constitutes an exciting area for mechanistic study with
      potential therapeutic implications.

PMID- 19840240
TI  - Daytime sleepiness, psychomotor performance, waking EEG spectra and evoked
      potentials in women with severe premenstrual syndrome.
AB  - We assessed daytime sleepiness using objective and subjective measures in women
      with severe premenstrual syndrome (PMS) compared with women without significant
      premenstrual symptoms. Nine women with severe PMS and eight controls (aged 18-40
      years) completed a laboratory-based daytime protocol including the maintenance of
      wakefulness test (MWT), psychomotor vigilance task (PVT), quantitative waking
      electroencephalogram (EEG), auditory and visual event-related potentials (ERPs),
      and sleepiness and mood scales during the mid-follicular and late-luteal
      (premenstrual) phases of the menstrual cycle. In association with increased
      perceived sleepiness, fatigue and other premenstrual symptoms in the late-luteal
      phase, women with PMS performed more poorly on the PVT, with increased lapses and
      slower reaction times (P < 0.05), compared with the follicular phase and
      controls. However, there were no significant group or menstrual phase differences
      in latency to sleep on the MWT. Waking spectral EEG power and ERP measures also
      did not differentiate PMS women when symptomatic. Both groups of women displayed
      increased spectral power in the delta/theta frequencies (2-6 Hz) and fast alpha
      frequency (11-12 Hz) in the late-luteal phase relative to the follicular phase.
      Trait-like differences were apparent in that women with PMS had increased beta1
      (12-16 Hz) power and smaller P300 amplitude than controls in both menstrual cycle
      phases. Our findings indicate that women with severe PMS are subjectively sleepy
      and fatigued, and show psychomotor slowing when symptomatic compared with when
      they are symptom-free and compared with controls. However, the ability to
      maintain wakefulness under soporific conditions, spectral properties of waking
      EEG and cognitive processing do not vary in synchrony with premenstrual symptoms.

PMID- 19840241
TI  - Sleep disturbances as a predictor of occupational injuries among public sector
      workers.
AB  - The association between disturbed sleep and increased risk of occupational injury
      has been observed in several cross-sectional and case-control studies, but
      prospective evidence is lacking. We examined prospectively whether sleep
      disturbances predicted occupational injuries in a large population of Finnish
      public sector employees. A total of 48 598 employees working in 10 municipalities
      and 21 hospitals in various parts of Finland were included. Sleep disturbances
      were assessed with the four-item Jenkins Sleep Problems Scale. Records of
      sickness absence due to occupational injury during the year following the survey
      were obtained from employers' registers. A proportion (9076; 22%) of participants
      reported disturbed sleep, and 978 (2.4%) had a recorded occupational injury.
      After adjustment for socio-demographic characteristics, the odds ratio (OR) for
      occupational injury was 1.38 [95% confidence interval (CI) 1.02-1.87] times
      higher for men with experiences of disturbed sleep than for those without sleep
      disturbances, but not significant for women. Of the sub-dimensions of sleep
      disturbances, the OR for occupational injury was 1.69 (95% CI 1.26-2.26) for
      women with difficulties initiating sleep, but not significant for men. These
      associations remained after additional adjustment for work stress, sleep length,
      obesity, alcohol use and mental health. This study suggests that sleep
      disturbances are a significant predictor of occupational injuries even after
      accounting for a range of covariates.

PMID- 19840242
TI  - Sleep and physical growth in infants during the first 6 months.
AB  - The aim of this study was to explore the relationships between infant sleep
      patterns and infant physical growth (weight for length ratio) using both
      objective and subjective sleep measures. Ninety-six first-born, healthy 6-month
      old infants and their parents participated in the study. Infant sleep was
      assessed by actigraphy for four consecutive nights and by the Brief Infant Sleep
      Questionnaire (BISQ). In addition, parents were asked to complete background and
      developmental questionnaires. Questions about feeding methods were included in
      the developmental questionnaire. Infants' weight and length were assessed during
      a standard checkup at the infant-care clinic when the infants were 6 months old.
      Significant correlations were found between infant sleep and growth after
      controlling for potential infant and family confounding factors. Actigraphic
      sleep percentage and reported sleep duration were correlated negatively with the
      weight-to-length ratio measures. Sex-related differences in the associations
      between sleep and physical growth were found. Breast feeding at night was
      correlated with a more fragmented sleep, but not with physical growth. These
      findings suggest that sleep is related significantly to physical growth as early
      as in the first months of life. The study supports increasing evidence from
      recent studies demonstrating a link between short sleep duration and weight gain
      and obesity in young children.

PMID- 19840243
TI  - Bargaining and trust: the effects of 36-h total sleep deprivation on socially
      interactive decisions.
AB  - Although it is well known that sleep loss results in poor judgement and
      decisions, little is known about the influence of social context in these
      processes. Sixteen healthy young adults underwent three games involving
      bargaining ('Ultimatum' and 'Dictator') and trust, following total sleep
      deprivation (TSD) and during rested wakefulness (RW), in a repeated-measures,
      counterbalanced design. To control for repeatability, a second group (n = 16) was
      tested twice under RW conditions. Paired anonymously with another individual,
      participants made their simple social interaction decisions facing real monetary
      incentives. For bargaining, following TSD participants were more likely to reject
      unequal-split offers made by their partner, despite the rejection resulting in a
      zero monetary payoff for both participants. For the trust game, participants were
      less likely to place full trust in their anonymous partner. Overall, we provide
      novel evidence that following TSD, the conflict between personal financial gain
      and payoff equality is focused upon avoidance of unfavourable inequality (i.e.
      unfairness). This results in the rejection of unfair offers at personal monetary
      cost, and the lack of full trust which would expose one to being exploited in the
      interaction. As such, we suggest that within a social domain decisions may be
      more influenced by emotion following TSD, which has fundamental consequences for
      real-world decision-making involving social exchange.

PMID- 19840244
TI  - Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case-control
      study in China.
AB  - BACKGROUND/AIMS: The risk factors for cholangiocarcinoma are incompletely defined
      in China, especially for intrahepatic cholangiocarcinoma (ICC). We evaluated the
      risk factors for both ICC and extrahepatic cholangiocarcinoma (ECC). METHODS: A
      case-control study in which cases were cholangiocarcinoma patients referred to
      Peking Union Medical College Hospital (PUMCH) between 1998 and 2008 and controls
      were healthy individuals. Controls were randomly selected from an existing
      database of healthy individuals at the Health Screening Center of PUMCH. Data on
      liver disease, family history, diabetes, smoking and drinking were collected by a
      retrospective review of the patients' records and health examination reports or
      by interview. RESULTS: A total of 190 patients (61 ICC; 129 ECC) and 380 age- and
      sex-matched controls were enrolled. HBsAg (P<0.001) and anti-HBc without HBsAg
      (P=0.001) were significantly related to ICC. The adjusted odds ratios (OR) and
      95% confidence intervals (CI) were 18.1 (95% CI: 7.5-44.0) and 3.6 (95% CI: 1.7
      7.6) respectively. Diabetes mellitus (P=0.007), cholecystolithiasis (P=0.004) and
      previous cholecystectomy (P<0.001) were significantly associated with ECC. The
      prevalence of cirrhosis was higher in ICC than that in ECC (P<0.001).
      Furthermore, on excluding the ICC patients with cirrhosis, ICC patients showed
      significant independent associations with HBsAg (OR: 7.3; 95% CI: 3.1-17.2) and
      anti-HBc without HBsAg (OR: 2.4; 95% CI: 1.1-5.2). CONCLUSION: Cirrhosis and
      chronic hepatitis B virus infection are risk factors for ICC, while
      cholecystolithiasis, diabetes and previous cholecystectomy are risk factors for
      ECC.

PMID- 19840245
TI  - Circulating and hepatic endocannabinoids and endocannabinoid-related molecules in
      patients with cirrhosis.
AB  - BACKGROUND/AIMS: Endocannabinoids include anandamide (AEA) and 2
      arachidonoylglycerol (2-AG). Endocannabinoid-related molecules like oleoyl
      ethanolamine (OEA) and palmitoyl-ethanolamine (PEA) have also been identified.
      AEA contributes to the pathogenesis of cardiovascular alterations in experimental
      cirrhosis, but data on the endocannabinoid system in human cirrhosis are lacking.
      Thus, we aimed to assess whether circulating and hepatic endocannabinoids are
      upregulated in cirrhotic patients and whether their levels correlate with
      systemic haemodynamics and liver function. METHODS: The endocannabinoid levels
      were measured in peripheral and hepatic veins and liver tissue by isotope
      dilution liquid chromatography-atmospheric pressure chemical ionization-mass
      spectrometry. Systemic haemodynamics were assessed by the transthoracic
      electrical bioimpedance technique. Portal pressure was evaluated by hepatic
      venous pressure gradient. RESULTS: Circulating AEA and, to a greater extent, PEA
      and OEA were significantly higher in cirrhotic patients than in controls. PEA and
      OEA were also increased in the cirrhotic liver tissue. AEA, OEA and PEA levels
      were significantly higher in peripheral than in the hepatic veins of cirrhotic
      patients, while the opposite occurred for 2-AG. Finally, circulating AEA, OEA and
      PEA correlated with parameters of liver function, such as serum bilirubin and
      international normalized ratio. No correlations were found with systemic
      haemodynamics. CONCLUSIONS: The endocannabinoid system is upregulated in human
      cirrhosis. Peripheral AEA is increased in patients with a high model of end-stage
      liver disease score and may reflect the extent of liver dysfunction. In contrast,
      the 2-AG levels, the other major endocannabinoid, are not affected by cirrhosis.
      The upregulation of the endocannabinoid-related molecules, OEA and PEA, is even
      greater than that of AEA, prompting pharmacological studies on these compounds.

PMID- 19840247
TI  - The c.504T>C (p.Asn168Asn) polymorphism in the ABCB4 gene as a predisposing
      factor for intrahepatic cholestasis of pregnancy in Greece.

PMID- 19840246
TI  - Nutritional status: its influence on the outcome of patients undergoing liver
      transplantation.
AB  - BACKGROUND: Malnutrition is frequently present in case of end-stage liver
      diseases, and in cirrhotic patients, a poor nutritional status is considered to
      be one of the predictive factors for increased morbidity and mortality rates
      after surgery. The impact of the recipients' malnutrition on the outcome of liver
      transplantation (LT) is still under debate and recent studies have shown
      controversial results. PATIENTS AND METHODS: We prospectively analysed the
      nutritional status of 38 consecutive patients undergoing LT in our University
      Hospital. Subjective global nutritional assessments (SGA) and anthropometry were
      used for the evaluation of the nutritional status. Energy expenditure, dietary
      intake and energy balance were also evaluated. After LT, multiple short-term
      outcomes that could be influenced by the nutritional status, such as number of
      episodes of infections (bacterial, viral and fungal) until discharge from
      hospital, length of stay in intensive care unit (ICU), length of hospital stay
      and in-hospital graft and patient's survival, were recorded. RESULTS:
      Malnutrition was identified in 53% of cases according to the SGA. Pretransplant
      nutritional status, haemoglobin levels and disease severity were independently
      associated with the number of infection episodes during the hospital stay. The
      presence of malnutrition was the only independent risk factor for the length of
      stay in the ICU and the total number of days spent in hospital. CONCLUSION: The
      present data suggest that recipients' malnutrition should be taken into account
      as a factor that increases complications and costs after LT.

PMID- 19840248
TI  - Epstein-Barr virus: is there any contribution to chronic hepatitis B and C?

PMID- 19840249
TI  - Non-alcoholic steatohepatitis induces non-fibrosis-related portal hypertension
      associated with splanchnic vasodilation and signs of a hyperdynamic circulation
      in vitro and in vivo in a rat model.
AB  - INTRODUCTION: Steatosis, without fibrosis, may lead to changes in liver blood
      flow, which are poorly understood, and to date have not been correlated to portal
      pressure and related haemodynamics. AIMS: To study the temporal relation between
      progressive steatosis, portal pressure, systemic haemodynamics, vascular
      responsiveness, mesenteric and portal blood flow in methionine-choline-deficient
      diet (MCDD)-fed rats. METHODS: Male Wistar rats fed the MCDD were examined at
      week (w) 0-1-2-3-4-5-6-7-8, respectively, including systemic haemodynamics and
      portal pressure. At w0-4-8, in vivo blood flow was measured in the portal vein
      and the superior mesenteric artery. Dose-response curves to phenylephrine (PE)
      were established in abdominal aortic rings. RESULTS: Histology showed 100%
      steatosis from w3 on. Fibrosis was absent. Significant inflammation was nearly
      absent upon w4. Portal pressure slightly increased at w2, reached a maximum at w4
      [9.4 +/- 0.3 vs 2.9 +/- 0.6 mmHg at w0 (P=0.003)] and remained stable upon w8.
      Mean arterial blood pressure (MABP) decreased from w2 on [98.7 +/- 5.7 mmHg on w4
      compared with 123.8 +/- 1.8 on w0 (P=0.002)]. Portal flow increased from 1.85 +/-
      0.11 to 3.07 +/- 0.44 ml/min/100 g on w0 and w8 respectively (P=0.039).
      Mesenteric artery flow increased from 3.40 +/- 0.26 to 4.56 +/- 0.30 ml/min/100 g
      on w0 and w8 respectively (P=0.043). Vascular responsiveness to PE gradually
      decreased from 138 +/- 3% on w0 to 110 +/- 5% on w4 (P=0.013). CONCLUSION:
      Steatohepatitis induces significant portal hypertension (PHT) in the absence of
      fibrosis, associated with an increase in mesenteric arterial and portal venous
      flow, arterial hyporesponsiveness to vasoconstrictors and a decrease in MABP,
      indicating the presence of splanchnic vasodilation and hyperdynamic circulation.
      These alterations resemble those seen in cirrhotic PHT.

PMID- 19840250
TI  - Hepatic changes of erythropoietin gene expression in a rat model of acute-phase
      response.
AB  - An acute-phase response is the systemic reaction of an organism to insult (e.g.
      infection, trauma and burning). It represents the 'first line' of defence of the
      body to tissue-damaging attacks. In the present work, we used a rat model of an
      intra-muscular turpentine oil (TO) injection to analyse erythropoietin (EPO) gene
      expression changes in the liver, one of the main target organs of acute-phase
      cytokines. EPO began to increase in the serum of TO-treated animals 6 h after
      injection and reached a maximum at 24 h (125+/-20 pg/ml). The detection of total
      RNA by polymerase chain reaction analysis showed that the levels of EPO gene
      expression in the liver were considerably increased between 2 and 12 h by up to
      20-fold at the peak after TO administration, followed by a gradual decrease over
      the next 48 h, although the values remained significantly higher compared with
      the control group. In the kidney, after a sudden slight increase, the values
      declined progressively to 3.5-fold decrease at 12 h after the injection. In the
      liver, a parallel upregulation of the hypoxia-inducible factor-1 (HIF-1) alpha
      gene was observed (up to 4.7-fold increase), while HIF-2 alpha gene expression
      remained unaltered. On the other hand, the protein of both genes became
      detectable after the injection and increased progressively over 24 h, with a
      subsequent decline. These results suggest that EPO may be added to the increasing
      group of positive acute-phase proteins and the liver might represent the major
      source of the hormone under these conditions in the rat.

PMID- 19840251
TI  - Ad36 adipogenic adenovirus in human non-alcoholic fatty liver disease.
AB  - AIMS: Infection with specific pathogens may lead to increased adiposity. The
      human adenovirus 36 (Ad36) is a relatively new factor in promoting adipogenesis.
      It seems to improve the metabolic profile, expanding adipose tissue and enhancing
      insulin sensitivity in animal models. The aim of this study was to investigate
      whether any association or predictor effect of Ad36 seropositivity is present in
      non-alcoholic fatty liver disease (NAFLD), a condition associated with obesity
      and insulin resistance (IR). METHODS: Sixty-five NAFLD patients and 114 controls
      were investigated. Ultrasound bright liver score (BLS), body composition, IR
      evaluated by homeostasis model assessment of insulin resistance index (HOMA or
      HOMA-IR) and serum neutralization assay for antibodies to Ad36 were assessed.
      RESULTS: Ad36-seropositive patients have a lower risk of bright liver [OR 0.505
      (95% confidence interval (CI) 0.265-0.962)]; greater IR leads to a higher risk of
      bright liver [OR 9.673 (95% CI 4.443-21.058)]. Among NAFLD, Ad36-seropositive vs.
      Ad36-seronegative patients did not show a significant IR difference. Ad36
      seropositive NAFLD patients, with the same levels of HOMA and BLS, had greater
      body mass index and body fat mass, in comparison with seronegative NAFLD
      patients. By a multiple linear regression model, BLS was explained by HOMA (beta
      0.513; P<0.0001), high density lipoprotein cholesterol (beta-0.219, P<0.006) and
      Ad36 seropositivity (beta-0.202, P<0.005); Ad36 seropositivity did not explain
      HOMA in the other multiple logistic regression model. CONCLUSIONS: Ad36
      seropositivity is not associated with a significant difference of IR in NAFLD
      patients, but is associated with a greater adiposity. Ad36 seropositivity is
      associated with a lower occurrence of NAFLD and bright liver, which, conceivably,
      is not directly mediated by IR.

PMID- 19840253
TI  - Quantitative HBsAg and HDV-RNA levels in chronic delta hepatitis.
AB  - Abstract Background: Hepatitis delta virus (HDV) causes severe liver disease.
      AIMS: To investigate the quantitative HDV-RNA, HBsAg and hepatitis B virus
      (HBV)DNA levels in correlation to histological, biochemical and demographical
      parameters in patients with chronic HDV infection as similar data in a large
      series of HDV patients are missing. METHODS: Eighty HDV patients were recruited
      in Germany, Turkey and Greece; quantitative determination of HDV-RNA, HBsAg and
      HBV-DNA was performed by real-time polymerase chain reaction, the Architect HBsAg
      assay and Cobas TaqMan HBV test respectively. RESULTS: All patients were infected
      with HDV-genotype 1. Thirty-five patients (48%) had significant fibrosis (Ishak 3
      4) and 15 (20.5%) had cirrhosis. HDV viraemia ranged from 1.1 x 10(3) to 8.4 x
      10(7) copies/ml with 60% of patients showing HDV-RNA levels above 10(5) copies/ml
      accompanied by low HBV viraemia (<10(5) copies/ml). However, HDV-RNA and HBV-DNA
      levels showed no direct inverse correlation. HDV-RNA correlated positively with
      HBsAg and negatively with age. HBsAg correlated negatively with age and
      positively with histological grading. Only gamma-glutamyltranspeptidase was
      independently associated with cirrhosis (P=0.032), while no biochemical parameter
      was associated with grading. CONCLUSIONS: (i) HBsAg levels correlated with HDV
      viraemia in chronic HDV. (ii) Biochemical parameters did not accurately indicate
      the stage and grade of liver disease in chronic HDV and thus liver biopsy seems
      to remain the major tool for the evaluation of delta hepatitis patients.

PMID- 19840254
TI  - Association between epidermal growth factor 61A/G polymorphism and hepatocellular
      carcinoma susceptibility in Chinese patients.
AB  - BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is an important
      risk factor for hepatocellular carcinoma (HCC) development in China, while little
      is known of the genetic susceptibility to hepatocarcinogenesis. The epidermal
      growth factor (EGF) pathway plays an important role in tumorigenesis, including
      HCC. EGF polymorphisms are associated with susceptibility to several types of
      cancers. Therefore, this study aimed to assess whether EGF genetic polymorphisms
      can influence HCC development. METHODS: A total of 338 chronic HBV-infected
      patients (186 HCC patients and 152 cirrhotic patients) and 186 healthy
      individuals were enrolled in this study. EGF 61A/G polymorphisms of all subjects
      and 12 cell lines were assayed with polymerase chain reaction-restriction
      fragment length polymorphism and the sequencing method. Furthermore, EGF protein
      levels were measured in the serum and the results were compared with the
      different genotypes. EGF expression in the liver tissue of the HCC patients was
      detected by immunohistochemical analysis. RESULTS: EGF 61A and 61G allele
      frequencies in healthy subjects were 28.76 and 71.24%. EGF 61GG and G allele
      frequencies in the HCC group were higher than those in the cirrhosis group. EGF
      protein levels with the GG genotype were significantly higher than those with
      either the GA or the AA genotype. About 59.09% of HCC liver tumour tissues
      assayed showed EGF protein expression. CONCLUSIONS: The EGF 61 GG genotype might
      be associated with a high risk for the development of chronic HBV infection
      related HCC in Chinese patients.

PMID- 19840255
TI  - Combined features of low phospholipid-associated cholelithiasis and progressive
      familial intrahepatic cholestasis 3.
AB  - Adenosine triphosphate-binding cassette, subfamily B, member 4 (ABCB4) gene
      alterations can cause two distinct clinical entities: progressive familial
      intrahepatic cholestasis type 3 (PFIC3) and low phospholipid-associated
      cholelithiasis (LPAC). Based on the findings in two siblings and a review of the
      literature, we aimed to identify determinants of disease phenotypic traits
      associated with ABCB4 gene alterations. Two siblings presented, before the age of
      30 years, recurrent symptomatic cholelithiasis and extensive biliary fibrosis
      that progressed towards portal hypertension and liver failure necessitating liver
      transplantation. We analysed the sequence of the ABCB4 gene and
      immunolocalization of the protein in the liver. Sequence analysis of ABCB11,
      potentially involved in similar symptoms, was also performed. Two heterozygous
      non-synonymous variants of ABCB4 were found in both siblings. One of them
      (c.959C>T; p.Ser320Phe) was previously implicated in LPAC and the second one
      (c.2858C>A; p.Ala953Asp) in PFIC3. Both patients were also heterozygous for the
      ABCB11 variant Val444Ala, which predisposes to cholestatic disorders. ABCB4 was
      normally detected at the canalicular membrane of hepatocytes. The review of ABCB4
      gene variants reported so far shows that the vast majority of variants causing
      PFIC3 and LPAC are distinct. Also as a general rule, homozygous variants cause
      PFIC3 while heterozygous variants lead to LPAC. Combined PFIC3 and LPAC phenotype
      is a rare clinical event, which may be determined by the coexistence of ABCB4
      variants related to both phenotypes and also potentially to the ABCB11 variant.
      Thus, most of the patients presenting with LPAC are not at a particular risk of
      developing PFIC3 features in adulthood.

PMID- 19840256
TI  - Current issues in the management of paediatric viral hepatitis.
AB  - Viral hepatitis poses important problems for children. In preschoolers, hepatitis
      A virus (HAV) infection frequently causes acute liver failure. Vaccinating
      toddlers against HAV in countries with high endemicity is expected to decrease
      mortality. HAV vaccine demonstrates efficacy (comparable to immunoglobulin) as
      post-exposure prophylaxis. A recently developed vaccine against hepatitis E virus
      (HEV) may benefit fetal health, because pregnant women are most prone to acute
      liver failure as a result of HEV. Hepatitis B vaccine continues to demonstrate
      value and versatility for preventing serious liver disease. With chronic
      infection, undetectable levels of serum HBV DNA complement e-seroconversion as
      the preferred outcome measure; suppressed viral load correlates with long-term
      complications better than HBeAg status. Among Taiwanese children, low
      pretreatment HBV DNA (<2 x 10(8) copies/ml) strongly predicted response to
      interferon-alpha. Future paediatric studies must incorporate HBV DNA levels. The
      rationale for routine treatment of immunotolerant hepatitis B during childhood
      remains uncertain. Any treatment of chronic hepatitis B in childhood requires
      consideration of the risks and benefits. Childhood hepatitis C virus (HCV)
      infection results mainly from mother-to-infant transmission. Babies of HCV
      infected women should be tested for serum HCV RNA at 1 month of age. If negative,
      confirmatory anti-HCV antibody testing may be performed between 12 and 15 months
      of age. Children with chronic hepatitis C may develop progressive
      fibrosis/cirrhosis, particularly in the setting of obesity and insulin
      resistance. Treatment of children chronically infected with genotype 2 or 3 is
      highly successful: combination therapy of pegylated interferon-alpha and
      ribavirin is well tolerated and superior to pegylated interferon-alpha alone.

PMID- 19840257
TI  - A prospective pilot study of circulating endothelial cells as a potential new
      biomarker in portal hypertension.
AB  - BACKGROUND/AIMS: Peripheral circulating endothelial cells (CEC) have been
      proposed as a prognostic marker in cardiovascular diseases. Cirrhosis and portal
      hypertension are associated with vascular injury yet little is known about CEC
      count in these conditions. Therefore, we evaluated CEC count in patients with
      cirrhosis, and correlated it with markers of portal hypertension/disease
      severity. PATIENTS/METHODS: Fifteen patients with cirrhosis/portal hypertension
      and 15 matched controls were prospectively recruited for study participation. An
      automated rare cell analysis system was used to enumerate CEC from peripheral
      blood and correlated with clinical features. RESULTS: Median CEC levels were
      significantly higher in patients with cirrhosis as compared with controls (median
      [interquartile range (IQR)]; cirrhosis: 73.7 cells/4 ml [53.7-140.3]; controls:
      28.7 cells/4 ml [21-58.7]; P=0.021). Ratio of CEC to platelet count (CEC/PC) also
      distinguished patients with cirrhosis from controls (IQR; cirrhosis: 0.723 [0.396
      1.672]; controls: 0.126 [0.103-0.333]; P<0.001). Receiver operator characteristic
      analysis revealed that CEC cut-off of 42 cells/4 ml showed sensitivity of 87% and
      specificity of 74% for differentiating cirrhosis from controls (AUC: 0.74), while
      CEC/PC ratio at 0.21 showed sensitivity of 100% and specificity of 73% (AUC:
      0.89). Furthermore, CEC/PC index was significantly elevated in patients with
      hepatic decompensation as defined by Child B/C (P<0.05). The intra- and
      interobserver variability correlation coefficients for CEC measurement were
      0.9989 and 0.9986 respectively. CONCLUSION: Median CEC count and CEC/PC ratio are
      significantly elevated in patients with cirrhosis, with CEC/PC also increased in
      patients with decompensated cirrhosis. These data provide rationale for larger
      validation studies to assess if CEC may have prognostic utility in patients with
      cirrhosis and portal hypertension.

PMID- 19840258
TI  - Risk of pancreatic cancer in chronic hepatitis B virus infection: data from the
      REVEAL-HBV cohort study.
AB  - BACKGROUND AND AIMS: The relationship between the hepatitis B virus (HBV) and
      pancreatic cancer remains unclear. Because HBV has been isolated from pancreatic
      tissue, we hypothesized that HBV may play a role in the development of pancreatic
      carcinoma. METHODS: This cohort was recruited between 1991 and 1992. Serum
      samples obtained at enrolment were tested for HBsAg and HBeAg by
      radioimmunoassay. Pancreatic cancer diagnosis was ascertained through data
      linkage with profiles of the National Cancer Registry and Death Certification
      System in Taiwan from 1 January 1991 to 31 December 2007. Multivariate-adjusted
      hazards ratios (HR(adj)) with 95% confidence intervals (CI) were derived using
      Cox proportional hazards models. RESULTS: In total 22 471 subjects were followed
      up for 342 186 person-years and 48 had pancreatic cancer. Chronic carriers of
      HBsAg had a significantly increased risk of pancreatic cancer showing an HR(adj)
      (95% CI) of 1.95 (1.01-3.78). This association was most striking in females,
      individuals < or =50 years, non-smokers and non-drinkers. The HR(adj) (95% CI) of
      developing pancreatic cancer was 5.73 (1.73-19.05) for HBeAg-seropositive
      carriers and 1.64 (0.79-3.42) for HBeAg-seronegative carriers compared with HBsAg
      seronegative non-carriers. An increased risk of pancreatic cancer was observed
      for HBsAg-seropositives with HBV DNA > or =300 copies/ml (HR(adj), 2.44; 95% CI,
      1.20-4.95), but not for HBsAg-seropositives with HBV DNA <300 copies/ml (HR(adj),
      0.64; 95% CI, 0.09-4.67). CONCLUSIONS: In addition to the well-established risk
      of hepatocellular carcinoma, chronic HBV infection may be associated with an
      increased risk of pancreatic cancer.

PMID- 19840259
TI  - Double-stranded RNA-activated protein kinase inhibits hepatitis C virus
      replication but may be not essential in interferon treatment.
AB  - BACKGROUND: Double-stranded RNA-activated protein kinase (PKR), an interferon
      (IFN)-stimulated gene, is activated by binding with double-stranded RNA, a
      putative replicative intermediate of the hepatitis C virus (HCV). Activated PKR
      phosphorylates the alpha subunit of eukaryotic initiation factor-2 to inhibit the
      translation of viral protein. AIMS/METHODS: We established stable PKR knockdown
      Huh7 cells using RNA interference and investigated the effect of PKR against HCV
      replication using a subgenomic replicon that expressed luciferase reporter
      protein and the JFH1 full-length HCV genome. RESULTS: In stable PKR knockdown
      cells that harboured a subgenomic replicon, luciferase activity was approximately
      three times higher than that of control cells, indicating that the subgenomic
      replicon replicated with a higher efficiency in stable PKR knockdown cells than
      that in control cells. Furthermore, stable PKR knockdown cells secreted
      significantly more HCV particles than did control cells after transfection with
      the full-length HCV genome. The replication of the subgenomic replicon was
      suppressed by the addition of IFN-alpha in both cells. Although the extent of
      suppression was significantly lower in stable PKR knockdown than control cells
      using a low concentration (2.5-5 U/ml) of IFN-alpha, even 10 U/ml IFN-alpha
      suppressed the replication of subgenomic replicon by >98% in both cells.
      CONCLUSIONS: Double-stranded RNA-activated protein kinase plays an important role
      in suppressing HCV replication in an innate state, but may not be essential in
      IFN therapy.

PMID- 19840260
TI  - A curvilinear lesion arising from the right lobe of liver.

PMID- 19840261
TI  - Female-biased dispersal under conditions of low male mating competition in a
      polygynous mammal.
AB  - Sex-biased dispersal is a common phenomenon in birds and mammals. Competition for
      mates has been argued to be an important selective pressure favouring dispersal.
      Sexual differences in the level of intrasexual competition may produce
      asymmetries in the costs-benefits balance of dispersal and philopatry for males
      and females, which may favour male-biased dispersal in polygynous species such as
      most mammals. This being the case, condition-dependent dispersal predicts that
      male-bias should decrease if mating competition relaxes. We test this expectation
      for red deer, where male-biased dispersal is the norm. In southwestern Spain, red
      deer populations located in nonfenced hunting estates presented altered
      structures with sex ratio strongly biased to females and high proportion of young
      males. As a consequence, mate competition in these populations was lower than in
      other, most typical red deer populations. We found that, under such conditions of
      altered population structure, dispersal was female-biased rather than male
      biased. Additionally, mate competition positively related to male dispersal but
      negatively to female dispersal. Other factors such as resource competition, age
      of individuals and sex ratio were not related to male or female dispersal. Males
      may not disperse if intrasexual competition is low and then females may disperse
      as a response to male philopatry. We propose hypotheses related to female mate
      choice to explain female dispersal under male philopatry. The shift of the sex
      biased dispersal pattern along the gradient of mate competition highlights its
      condition-dependence as well as the interaction between male and female dispersal
      in the evolution of sex-biased dispersal.

PMID- 19840262
TI  - Identifying glacial refugia in a geographic parthenogen using palaeoclimate
      modelling and phylogeography: the New Zealand stick insect Argosarchus horridus
      (White).
AB  - We have used phylogeographic analysis of mitochondrial DNA (COI and COII genes)
      and ecological niche modelling (ENM) to reconstruct the population history of
      Argosarchus horridus (White), a widespread species of New Zealand stick insect.
      These data were used to address outstanding questions on the role of glacial
      refugia in determining the distribution and genetic structure of New Zealand
      species. Phylogeographic analysis shows a general pattern of high diversity in
      upper North Island and reduced diversity in lower North Island and South Island.
      The ENM indicates that during the last glacial maximum, A. horridus was largely
      restricted to refugia around coastal areas of North Island. The ENM also suggests
      refugia on the northeast coast of South Island and southeast coast of North
      Island and this prediction is verified by phylogeographic analysis, which shows a
      clade restricted to this region. Argosarchus horridus is also most likely a
      geographic parthenogen where males are much rarer at higher latitudes. The higher
      levels of genetic variation in northern, bisexual populations suggest southern
      and largely unisexual populations originated from southwardly expanding
      parthenogenetic lineages. Bayesian skyline analysis also provides support for a
      recent population size increase consistent with a large increase in geographic
      distribution in the late Pleistocene. These results exemplify the utility of
      integrating ENM and phylogeographic analysis in testing hypotheses on the origin
      of geographic parthenogenesis and effects of Pleistocene environmental change on
      biodiversity.

PMID- 19840263
TI  - Amphibian chytridiomycosis in Japan: distribution, haplotypes and possible route
      of entry into Japan.
AB  - A serious disease of amphibians caused by the chytrid fungus Batrachochytrium
      dendrobatidis was first found in Japan in December 2006 in imported pet frogs.
      This was the first report of chytridiomycosis in Asia. To assess the risk of
      pandemic chytridiomycosis to Japanese frogs, we surveyed the distribution of the
      fungus among captive and wild frog populations. We established a nested PCR assay
      that uses two pairs of PCR primers to amplify the internal transcribed spacer
      (ITS) region of a ribosomal RNA cassette to detect mild fungal infections from as
      little as 0.001 pg (1 fg) of B. dendrobatidis DNA. We collected swab samples from
      265 amphibians sold at pet shops, 294 bred at institutes and 2103 collected at
      field sites from northern to southwestern Japan. We detected infections in native
      and exotic species, both in captivity and in the field. Sequencing of PCR
      products revealed 26 haplotypes of the B. dendrobatidis ITS region. Phylogenetic
      analysis showed that three of these haplotypes were specific to the Japanese
      giant salamander (Andrias japonicus) and appeared to have established a commensal
      relationship with this native amphibian. Many other haplotypes were carried by
      alien amphibians. The highest genetic diversity of B. dendrobatidis was found in
      the American bullfrog (Rana catesbeiana). Some strains of B. dendrobatidis
      appeared to be endemic to Japanese native amphibians, but many alien strains are
      being introduced into Japan via imported amphibians. To improve chytridiomycosis
      risk management, we must consider the risk of B. dendrobatidis changing hosts as
      a result of anthropogenic disturbance of the host-specific distribution of the
      fungus.

PMID- 19840264
TI  - Genetic variability is unrelated to growth and parasite infestation in natural
      populations of the European eel (Anguilla anguilla).
AB  - Positive correlations between individual genetic heterozygosity and fitness
      related traits (HFCs) have been observed in organisms as diverse as plants,
      marine bivalves, fish or mammals. HFCs are not universal and the strength and
      stability of HFCs seem to be variable across species, populations and ages. We
      analysed the relationship between individual genetic variability and two
      different estimators of fitness in natural samples of European eel, growth rate
      (using back-calculated length-at-age 1, 2 and 3) and parasite infestation by the
      swimbladder nematode Anguillicola crassus. Despite using a large data set of 22
      expressed sequence tags-derived microsatellite loci and a large sample size of
      346 individuals, no heterozygote advantage was observed in terms of growth rate
      or parasite load. The lack of association was evidenced by (i) nonsignificant
      global HFCs, (ii) a Multivariate General Linear Model showing no effect of
      heterozygosity on fitness components, (iii) single-locus analysis showing a lower
      number of significant tests than the expected false discovery rate, (iv) sign
      tests showing only a significant departure from expectations at one component,
      and, (v) a random distribution of significant single-locus HFCs that was not
      consistent across fitness components or sampling sites. This contrasts with the
      positive association observed in farmed eels in a previous study using allozymes,
      which can be explained by the nature of the markers used, with the allozyme study
      including many loci involved in metabolic energy pathways, while the expressed
      sequence tags-linked microsatellites might be located in genes or in the
      proximity of genes uncoupled with metabolism/growth.

PMID- 19840266
TI  - A comment on Garcia et al. (2005, 2007) and related papers on mating patterns and
      gene dispersal in Prunus mahaleb.
AB  - In two studies on mating patterns and spatial components of pollen and seed
      dispersal of Prunus mahaleb based on parentage analysis, Garcia et al. (2005,
      2007) depicted their 196 focal trees as a spatially isolated population where all
      reproductive trees had been genotyped. Additional distributional data for P.
      mahaleb trees in their study area, however, revealed that Garcia and colleagues'
      depiction of their study system bears little resemblance to reality. The trees
      these authors studied did not form a discrete, geographically isolated
      population. Around 300 ungenotyped reproductive trees occurred within the 1.5-km
      distributional gap to the nearest population proclaimed by Garcia and colleagues.
      Since exhaustive sampling of potential parental genotypes is essential in
      parentage analyses, the occurrence of a large number of ungenotyped trees in the
      immediate neighbourhood of focal trees can severely affect the main conclusions
      of Garcia et al. (2005, 2007) as well as of several related publications on gene
      dispersal and mating patterns of P. mahaleb conducted on the same trees and
      relying on the same false premises of spatial isolation and exhaustive sampling.

PMID- 19840267
TI  - An AFLP clock for absolute dating of shallow-time evolutionary history--too good
      to be true?
AB  - A major drawback of Amplified Fragment Length Polymorphisms (AFLP) as genetic
      makers for phylogeographic studies is their lack of a temporal dimension. In a
      recent publication in Molecular Ecology, Kropf et al. (2009) proposed a molecular
      clock for AFLP. In this comment we evaluate the proposed approach both
      theoretically and empirically. A linear increase with time is a prerequisite to
      use a genetic distance as molecular clock. Testing the relationship between
      genetic distance and time in the data of Kropf et al. (2009) for linearity
      revealed that the relationship was in fact not linear for their pooled data, as
      well as for one of the three species analyzed. Also, the relationship was not
      linear in two new species, where divergence times could be inferred from
      macrofossils. When applying the proposed molecular clock to data from eight
      species, dates obtained were plausible in some cases, but very improbable in
      others. The suggested genetic distance was also influenced by intrapopulation
      genetic diversity, leading to a potential bias. In the future, investigations of
      AFLP mutation rates combined with phylogeographic modelling may contribute to
      adding a time scale to the understanding of AFLP data.

PMID- 19840268
TI  - Genetic epidemiology of the sudden oak death pathogen Phytophthora ramorum in
      California.
AB  - A total of 669 isolates of Phytophthora ramorum, the pathogen responsible for
      Sudden Oak Death, were collected from 34 Californian forests and from the
      ornamental plant-trade. Seven microsatellite markers revealed 82 multilocus
      genotypes (MGs) of which only three were abundant (>10%). Iteratively collapsing
      based upon minimum Phi(ST), yielded five meta-samples and five singleton
      populations. Populations in the same meta-sample were geographically contiguous,
      with one exception, possibly explained by the trade of infected plants from the
      same source into different locations. Multidimensional scaling corroborated this
      clustering and identified nursery populations as genetically most distant from
      the most recent outbreaks. A minimum-spanning network illustrated the
      evolutionary relationships among MGs, with common genotypes at the centre and
      singletons at the extremities; consistent with colonization by a few common
      genotypes followed by local evolution. Coalescent migration analyses used the
      original data set and a data set in which local genotypes were collapsed into
      common ancestral genotypes. Both analyses suggested that meta-samples 1 (Santa
      Cruz County) and 3 (Sonoma and Marin Counties), act as sources for most of the
      other forests. The untransformed data set best explains the first phases of the
      invasion, when the role of novel genotypes may have been minimal, whereas the
      second analysis best explains migration patterns in later phases of the invasion,
      when prevalence of novel genotypes was likely to have become more significant.
      Using this combined approach, we discuss possible migration routes based on our
      analyses, and compare them to historical and field observations from several case
      studies.

PMID- 19840269
TI  - Ghrelin stimulates gastric motility of the guinea pig through activation of a
      capsaicin-sensitive neural pathway: in vivo and in vitro functional studies.
AB  - BACKGROUND: Ghrelin stimulates gastric motility in rats, mice and humans.
      Although ghrelin and the ghrelin receptor are known to be expressed in the guinea
      pig gastrointestinal tract, the effects of ghrelin on gastric motility have not
      been examined. Aim of the present study was to clarify the motor-stimulating
      action of ghrelin in the guinea-pig stomach. METHODS: Gastric motility was
      measured as intraluminal pressure changes using a balloon inserted in the stomach
      of urethane-anaesthetized guinea pigs. The effects of ghrelin on gastric muscle
      contraction and [(3)H]-efflux from [(3)H]-choline-loaded strips were investigated
      in vitro. KEY RESULTS: Ghrelin (0.3-30 microg kg(-1), i.v.) increased gastric
      motility in a dose-dependent manner but des-acyl ghrelin was ineffective. The
      action of ghrelin was completely inhibited by hexamethonium and D-Lys(3)-growth
      hormone releasing peptide-6. Atropine partially decreased the stimulatory action
      of ghrelin. In capsaicin-pretreated guinea pigs, the ghrelin-induced response was
      markedly decreased. Ghrelin (1 micromol L(-1)) did not affect [(3)H]-efflux in
      non-stimulated preparations but significantly decreased electrical field
      stimulation (EFS)-induced [(3)H]-efflux. L-Nitro arginine methylester (L-NAME)
      attenuated the inhibition of [(3)H]-efflux by ghrelin. Ghrelin did not cause any
      mechanical changes in gastric strips. Electrical field stimulation caused
      relaxation of gastric strips, which changed to atropine-sensitive contraction in
      the presence of L-NAME. Relaxation induced by EFS was slightly potentiated, but
      the EFS-induced contraction was not affected by ghrelin. CONCLUSIONS &
      INFERENCES: Ghrelin stimulates gastric motility of the guinea pig through
      activation of capsaicin-sensitive vago-vagal reflex pathway including efferent
      cholinergic neurons. Peripheral ghrelin receptors on enteric nitrergic nerves
      might affect the ghrelin-induced gastric action by releasing nitric oxide.

PMID- 19840270
TI  - Involvement of cannabinoid-1 and cannabinoid-2 receptors in septic ileus.
AB  - BACKGROUND Cannabinoid (CB) receptors are involved in the regulation of
      gastrointestinal (GI) motility under physiological and pathophysiological
      conditions. We aimed to characterize the possible influence of CB(1) and CB(2)
      receptors on motility impairment in a model of septic ileus. METHODS
      Lipopolysaccharide (LPS) injections were used to mimic pathophysiological
      features of septic ileus. Spontaneous jejunal myoelectrical activity was measured
      in rats in vivo, and upper GI transit was measured in vivo by gavaging of a
      charcoal marker into the stomach of mice, in absence or presence of LPS, and
      CB(1) and CB(2) receptor agonists and antagonists. Tumour necrosis factor (TNF)
      alpha and interleukin (IL)-6 levels were measured using enzyme-linked
      immunosorbent assay. Histology was performed with haematoxylin-eosin staining.
      KEY RESULTS Lipopolysaccharide treatment significantly reduced amplitude and
      frequency of myoelectric spiking activity and GI transit in vivo in a dose
      dependent manner. TNF-alpha and IL-6 were increased in LPS-treated animals and
      histology showed oedema and cell infiltration. Both, the CB(1) agonist HU210 and
      the CB(2) agonist JWH133 reduced myoelectrical activity whereas the CB(1)
      antagonist AM251 caused an increase of myoelectrical activity. Pretreatment with
      AM251 or AM630 prevented against LPS-induced reduction of myoelectrical activity,
      and also against the delay of GI transit during septic ileus in vivo. CONCLUSIONS
      & INFERENCES The LPS model of septic ileus impairs jejunal myoelectrical activity
      and delays GI transit in vivo. Antagonists at the CB(1) receptor or the CB(2)
      receptor prevent the delay of GI transit and thus may be powerful tools in the
      future treatment of septic ileus.

PMID- 19840271
TI  - Unexplained gastrointestinal symptoms and joint hypermobility: is connective
      tissue the missing link?
AB  - BACKGROUND Unexplained gastrointestinal (GI) symptoms and joint hypermobility
      (JHM) are common in the general population, the latter described as benign joint
      hypermobility syndrome (BJHS) when associated with musculo-skeletal symptoms.
      Despite overlapping clinical features, the prevalence of JHM or BJHS in patients
      with functional gastrointestinal disorders has not been examined. METHODS The
      incidence of JHM was evaluated in 129 new unselected tertiary referrals (97
      female, age range 16-78 years) to a neurogastroenterology clinic using a
      validated 5-point questionnaire. A rheumatologist further evaluated 25 patients
      with JHM to determine the presence of BJHS. Groups with or without JHM were
      compared for presentation, symptoms and outcomes of relevant functional GI tests.
      KEY RESULTS Sixty-three (49%) patients had evidence of generalized JHM. An
      unknown aetiology for GI symptoms was significantly more frequent in patients
      with JHM than in those without (P < 0.0001). The rheumatologist confirmed the
      clinical impression of JHM in 23 of 25 patients, 17 (68%) of whom were diagnosed
      with BJHS. Patients with co-existent BJHS and GI symptoms experienced abdominal
      pain (81%), bloating (57%), nausea (57%), reflux symptoms (48%), vomiting (43%),
      constipation (38%) and diarrhoea (14%). Twelve of 17 patients presenting with
      upper GI symptoms had delayed gastric emptying. One case is described in detail.
      CONCLUSIONS & INFERENCES In a preliminary retrospective study, we have found a
      high incidence of JHM in patients referred to tertiary neurogastroenterology care
      with unexplained GI symptoms and in a proportion of these a diagnosis of BJHS is
      made. Symptoms and functional tests suggest GI dysmotility in a number of these
      patients. The possibility that a proportion of patients with unexplained GI
      symptoms and JHM may share a common pathophysiological disorder of connective
      tissue warrants further investigation.

PMID- 19840272
TI  - Decrease in nerve fibre density in human sigmoid colon circular muscle occurs
      with growth but not aging.
AB  - BACKGROUND: Studies in animals suggest that enteric neurons decrease in density
      or number with increasing age. Neurons containing nitric oxide (NO), vasoactive
      intestinal peptide (VIP) and Substance P (SP) have been implicated. In human
      large intestine, NO-utilizing neurons decrease during childhood or early
      adulthood but it is not known if the innervation of the muscle changes. This
      study examined the density of nerve fibres containing these transmitters in
      sigmoid colon circular muscle from children and adults. METHODS: Fluorescence
      immunohistochemistry using antibodies to neuronal NO synthase (nNOS), VIP and SP
      was performed on sigmoid colon from 18 adults with colorectal cancer, two
      children with familial adenomatous polyposis, and normal colon from nine children
      with Hirschsprung's disease. The percentage area of immunoreactive (IR) nerve
      fibres containing each transmitter in circular muscle was quantified in confocal
      images. KEY RESULTS: In the adult sigmoid colon circular muscle, the percentage
      area of nerve fibres containing nNOS>VIP>SP (6 : 2 : 1). Paediatric groups had
      significantly higher percentage area of nerve fibres containing nNOS, VIP or SP
      IR than adults, with the decrease in nerve fibre density occurring from birth to
      30 years. Circular muscle thickness increased between 12 and 30 years. Total
      nerve fibre area remained constant, while the muscle increased in thickness.
      CONCLUSIONS & INFERENCES: In human sigmoid colon circular muscle, there are
      reductions in nNOS-, VIP- and SP-IR nerve fibre density with growth from newborn
      to late adolescence but little further change with aging. The reduction in nerve
      density is due to an increase in circular muscle thickness rather than a loss of
      nerve fibres.

PMID- 19840273
TI  - Carbon emissions: can I make a difference?

PMID- 19840274
TI  - Recovering from the psychological impact of intensive care: how constructing a
      story helps.
AB  - BACKGROUND: Numerous studies have demonstrated both the risk of post-traumatic
      stress as a result of intensive care unit (ICU) treatment and the efficacy of
      successful narrative processing for recovery from psychological trauma. AIM: This
      article is based on recent doctoral research exploring the impact of
      unanticipated life threats after admission to hospital. It examines the
      difficulties ICU patients have with constructing coherent narratives of their
      illness experience and the significance of those difficulties for psychological
      recovery from critical illness. METHODS: The original research used a qualitative
      design blending discourse, narrative, and phenomenological approaches guided by
      hermeneutical sensitivity to the evolving language of narrative processing.
      Patients chosen from ICU discharge summaries showing a critical life-threatening
      event after admission to hospital were interviewed soon after discharge from
      hospital and then again 1 year later. Unstructured interviews explored
      participant experience of a critical event and its aftermath. RESULTS: This
      article focuses in particular on one finding from the doctoral research.
      Unanticipated critical illness presented some patients with difficulties in
      accomplishing the fundamental human task of constructing a narrative of their
      experience. Risk factors were observed identifying specific vulnerabilities. The
      extent to which difficulties were overcome impacted positively on the patient's
      sense of well-being 1 year after discharge. CONCLUSIONS: In order to recover
      psychologically, some ICU patients need help overcoming obstacles to their
      ability to construct an adequately coherent narrative of their experience.
      RELEVANCE TO CLINICAL PRACTICE: ICU follow-up clinics could gain increased
      clarity of purpose from this narrative conceptual framework, eventually
      evaluating and validating benchmarks for assessing psychological recovery in
      relation to specified dimensions of narrative processing. Practice development
      informed by narrative process theory could also enhance ICU nursing
      communication. Since story construction is central to a person's core identity
      processes, person-centred nursing would also be implicated.

PMID- 19840275
TI  - The importance of knowing the patient in weaning from mechanical ventilation.
AB  - AIM: The aim of the research was to understand how nurses used technology to wean
      patients from mechanical ventilation. BACKGROUND: The literature concerned with
      the development of critical care centres on the role of technology with little
      emphasis on the nursing contribution. DESIGN: An ethnographic approach was used
      to understand how nurses used technology to wean patients from mechanical
      ventilation. METHODS: Data were gathered by participant observation and
      interviewing over a 6-month period. In total, 250 h of field notes were recorded.
      RESULTS: Data were analysed by the content analysis method. Knowing the patient
      was a central theme identified. Three sub-themes were identified: ways of
      knowing, continuity of care and the role of the patient in the weaning
      trajectory. CONCLUSION: 'Knowing the patient' was implied during the interviews
      as essential to the delivery of patient-centred care. There were two main factors
      that needed to be present in order for nurses to know their patients: continuity
      of care and expertise. 'Ways of knowing' was reliant on gaining information about
      the patient. The role of the patient was a passive recipient of treatment.
      IMPLICATIONS FOR PRACTICE: Knowing the patient has been defined as a
      characteristic of expert nursing. To be truly patient-centred nursing needs to
      address the barriers that prevent nurses from getting to 'know' their patients.

PMID- 19840276
TI  - The immediate life support course: implementation into an undergraduate nursing
      programme.
AB  - AIM: The aim of this paper is to outline how the immediate life support (ILS)
      course was incorporated into an undergraduate nursing curriculum in a university
      in Northern Ireland. It also reports on how the students perceived the impact of
      this course on their clinical practice. RATIONALE AND BACKGROUND: The rationale
      of the course was to develop the student's ability to recognize the acutely ill
      patient and to determine the relevance of this to clinical practice. Prior to
      this, the ILS course was only available to qualified nurses, and this paper
      reports on the first time undergraduate nursing students were provided with an
      ILS course. METHODS: The ILS course was delivered to 89 third-year nursing
      students from the adult branch pathway of the BSc (Hons) programme in Nursing
      Sciences. Each course was taught to 10-12 students and was completed over eight
      7.5 h sessions within a 2-week period. Recognized advanced life support (ALS)
      instructors, in keeping with the UK Resuscitation Council guidelines, taught the
      students. RESULTS AND CONCLUSION: Student feedback reported that the ILS course
      helped them understand what constituted the acutely ill patient and the role of
      the nurse in managing a deteriorating situation. Students also reported that they
      valued the experience as highlighting gaps in their knowledge.

PMID- 19840277
TI  - Arterial transducer placement and cerebral perfusion pressure monitoring: a
      discussion.
AB  - AIM: To discuss existing disparity of practice and clinical implications of
      measuring cerebral perfusion pressure (CPP) from differing reference points thus
      highlighting the need for standardized benchmarks. BACKGROUND: When managing
      traumatic brain injury (TBI), the arterial transducer level is a key to an
      accurate CPP reading; however, there is a lack of national standards about where
      to zero arterial transducers when monitoring CPP. METHODS: A systematized search
      using the Cochrane library database, Pubmed database, Medline, British Library on
      line, CINAHL and PROQUEST using key search terms was used to identify articles
      that could form a basis for a discussion. Papers published between 2000 and 2008
      were included. Papers that did not discuss arterial transducer level placement
      and CPP were excluded. The Brian Trauma Guidelines 2007 were scrutinized for
      recommendations. RESULTS: Of 57 empirical studies accessed, none reported or
      explored the placement of the arterial transducer during CPP measurement.
      Conflicting opinions were identified within the literature and there were no
      recommendations made for practice within the Brain Trauma Foundation Guidelines
      2007. DISCUSSION: At the present time, there is insufficient evidence for
      recommending standard placement for mean arterial pressure (MAP) measurements for
      patients with TBI. There are implications to consider as the treatment prescribed
      will differ depending on where the arterial transducer is placed because the MAP
      and CPP displayed will fall by 15 mm Hg at a head elevation of 30 degrees. This
      poses a number of questions: is the CPP underestimated with the arterial
      transducer placed at head level? Is the CPP overestimated if the transducer is
      placed at mid axilla level? RECOMMENDATIONS: Further research is recommended.
      However, studies would be difficult to power as head-injured patients constitute
      a heterogeneous population. Professional consensus should be applied and
      standardized benchmarks agreed.

PMID- 19840278
TI  - BACCN International Conference 2009- 'an international perspective: cementing
      alliances and forging success'.

PMID- 19840279
TI  - Face shape of unaffected parents with cleft affected offspring: combining three
      dimensional surface imaging and geometric morphometrics.
AB  - OBJECTIVE: Various lines of evidence suggest that face shape may be a
      predisposing factor for non-syndromic cleft lip with or without cleft palate
      (CL/P). In the present study, 3D surface imaging and statistical shape analysis
      were used to evaluate face shape differences between the unaffected (non-cleft)
      parents of individuals with CL / P and unrelated controls. METHODS: Sixteen
      facial landmarks were collected from 3D captures of 80 unaffected parents and 80
      matched controls. Prior to analysis, each unaffected parent was assigned to a
      subgroup on the basis of prior family history (positive or negative). A geometric
      morphometric approach was utilized to scale and superimpose the landmark
      coordinate data (Procrustes analysis), test for omnibus group differences in face
      shape, and uncover specific modes of shape variation capable of discriminating
      unaffected parents from controls. RESULTS: Significant disparity in face shape
      was observed between unaffected parents and controls (p < 0.01). Notably, these
      changes were specific to parents with a positive family history of CL/P. Shape
      changes associated with CL/P predisposition included marked flattening of the
      facial profile (midface retrusion), reduced upper facial height, increased lower
      facial height, and excess interorbital width. Additionally, a sex-specific
      pattern of parent-control difference was evident in the transverse dimensions of
      the nasolabial complex. CONCLUSIONS: The faces of unaffected parents from
      multiplex cleft families displayed meaningful shape differences compared with the
      general population. Quantitative assessment of the facial phenotype in cleft
      families may enhance efforts to discover the root causes of CL/P.

PMID- 19840280
TI  - Effects of relaxin on collagen type I released by stretched human periodontal
      ligament cells.
AB  - OBJECTIVES: Relapse of teeth that have moved during orthodontic treatment is a
      major clinical issue with respect to the goals of successful treatment. Such
      relapse is a physiologic response of the supporting tissues to application of
      force, and is mainly attributed to occlusal instability and increased mechanical
      tension exerted by the periodontal ligament (PDL). Relaxin, a member of the
      insulin/relaxin family of structurally related hormones, has an influence on many
      physiologic processes, such as collagen turnover, angiogenesis, and antifibrosis.
      Therefore, relaxin may also affect orthodontic tooth movement through alterations
      of the PDL, though little is known regarding the relationship between relaxin and
      stretched human PDL (hPDL) cells. In the present study, we investigated the
      effects of relaxin on the expression of collagen type I (Col-I) and matrix
      metalloproteinase 1 (MMP-1) in stretched hPDL cells in vitro. MATERIALS AND
      METHODS: The release and gene expression of Col-I, as well as those of MMP-1 in
      stretched hPDL cells treated with relaxin were investigated using enzyme-linked
      immunosorbent assay and real-time PCR methods. RESULTS: Relaxin decreased the
      release and gene expression of Col-I, and increased those of MMP-1 by stretched
      hPDL cells in a magnitude-dependent manner. CONCLUSION: Our results indicate that
      relaxin modulates collagen metabolism in stretched hPDL cells via the release and
      expression of Col-I and MMP-1. This hormone may be useful to prevent orthodontic
      relapse following orthodontic treatment.

PMID- 19840281
TI  - Low-energy laser irradiation accelerates the velocity of tooth movement via
      stimulation of the alveolar bone remodeling.
AB  - INTRODUCTION: Previously, the authors have reported the acceleration of tooth
      movement and osteoclastogenesis on the pressure site in an experimental tooth
      movement model by low-energy laser irradiation (LELI), which stimulated the
      RANK/RANKL system and c-fms/macrophage colony-stimulating factor system. However,
      the effect of LELI on osteogenesis on the tension site is not known clearly.
      Moreover, the temporal changes in alveolar bone during tooth movement have not
      been investigated as yet. Therefore, the present study was designed to examine
      the effects of LELI on alveolar bone remodeling during experimental tooth
      movement, and observe the temporal bone mineral density (BMD) using micro
      computed tomography (muCT). MATERIALS AND METHODS: To induce experimental tooth
      movement in rats, 10 g force was applied to the upper right first molar with
      Nickel titanium closed-coil. Next, a gallium-aluminum-arsenide (Ga-Al-As) diode
      laser was used to irradiate the area around the moved tooth, and BMD and the
      amount of tooth movement were measured by muCT scanning for 21 days.
      Histopathological examination was also performed. RESULTS: The amount of tooth
      movement in the LELI group was significantly greater than in the non-irradiation
      group by the end of the experimental period. Further, compared with the non
      irradiation group, the fall of BMD was less in the LELI group. CONCLUSION: These
      findings suggest that LELI accelerates the velocity of tooth movement via
      stimulation of the alveolar bone remodeling.

PMID- 19840282
TI  - Comparison of cortical bone thickness and root proximity at maxillary and
      mandibular interradicular sites for orthodontic mini-implant placement.
AB  - OBJECTIVES: To compare maxillary and mandibular cortical bone thickness and
      rootic proximity for optimal mini-implant placement. SETTING AND SAMPLE
      POPULATION: CT images from 14 men and 14 women were used to evaluate buccal
      interradicular cortical bone thickness and root proximity from mesial of the
      central incisor to the 2nd molar. Cortical bone thickness was measured at 0
      degrees , 15 degrees , 30 degrees , and 45 degrees angles relative to the root
      surface using three-dimensional images. RESULTS: For the cortical bone thickness,
      there was no statistically significant difference between the maxilla and the
      mandible in the anterior area; however, there was a significant difference in the
      posterior area. Cortical bone in the maxilla, mesial and distal to canine
      interradicular sites, was thickest while thickness in the mandible exhibited a
      gradual anterior to posterior increase. Cortical bone thickness in the maxilla
      increased as both level and angle increased, while the cortical bone thickness in
      the mandible was greatest at 4 mm from the alveolar crest. Root proximity mesial
      and distal to 2nd premolar interradicular sites was greatest. CONCLUSION: Based
      on our results, cortical bone thickness depends on the interradicular site rather
      than sex or individual differences.

PMID- 19840283
TI  - Forces and moments on posterior teeth generated by incisor intrusion
      biomechanics.
AB  - OBJECTIVES: To comparatively evaluate the extrusive forces and torquing moments
      on the posterior dentition generated during anterior intrusion with different
      intrusion techniques in the maxillary and mandibular dental arch. MATERIAL AND
      METHODS: Seven wire specimens were used for each of the following intrusive
      arches: Utility arch 0.016 x 0.016' Blue Elgiloy, Utility arch 0.017 x 0.025' TMA
      and Burstone Intrusion arch 0.017 x 0.025' TMA. The wires were inserted on
      bracketed dental arches constructed on maxillary Frasaco models, segmented
      mesially to the maxillary canines. Simulated intrusion from 0.0-3.0 mm was
      performed on the Orthodontic Measurement and Simulation System (OMSS). The forces
      and moments were recorded in all three planes of space at 0.1 mm increments and
      the values at 3.0 mm for all wires were used for all statistical evaluations. The
      data were analyzed, separately for the forces and moments, by means of two-way
      analysis of variance (ANOVA) with forces and moments serving as the dependent
      variables and intrusion technique and jaw (maxilla or mandible) as the
      independent variable. Post hoc multiple comparisons were performed using the
      Tukey test at .05 error rate. RESULTS: The 0.016 x 0.016' Blue Elgiloy utility
      arch exerted the highest posterior extrusive forces, 15% higher than the 0.017 x
      0.025' TMA utility and 40% higher in comparison with the 0.017 x 0.025' TMA
      Burstone intrusion arch.The lowest posterior moment in the sagittal plane was
      generated by the 0.017 x 0.025' TMA Burstone intrusion arch. The 0.016 x 0.016'
      Blue Elgiloy utility arch exerted 15% higher posterior moments and the 0.017 x
      0.025' TMA utility 25% higher. Forces and moments were consistently larger for
      the mandible compared to the maxilla for the same intrusion technique.
      CONCLUSIONS: The upper Burstone 0.017 x 0.025' TMA intrusion arch exerted the
      lowest forces/moments on posterior teeth. The highest forces were generated by
      the 0.016 x 0.016-inch Blue Elgiloy utility arch and the highest moments by the
      lower 0.017 x 0.025-inch TMA utility arch.

PMID- 19840284
TI  - Simplified stress analysis on the temporomandibular joint in Class III patients
      with and without mandibular asymmetry using a rigid body spring model.
AB  - OBJECTIVE: Aim of this study was to investigate the differences in stress on the
      temporomandibular joint (TMJ) between Class III patients with and without
      mandibular asymmetry using a rigid body spring model (RBSM). DESIGN: Menton (Me),
      the centre point of occlusal force on the line that connected the bilateral
      buccal cusps of the second molars and the most lateral, superior and medial
      points of the condyle were plotted on frontal cephalograms, and stress on the
      condyles was calculated with the 2-dimensional RBSM program of fortran. SETTING
      AND SAMPLE POPULATION: Eighty Japanese patients with diagnosed mandibular
      prognathism were divided into two groups, a symmetry group and asymmetry group on
      the basis of the Mx-Md midline position. OUTCOME MEASURE: The degree (force
      partition) of the resultant force, the direction (angulation) and displacement
      (X, Y) of each condyle were calculated. The horizontal displacement vector (u),
      the vertical displacement vector (v) and rotation angle (theta) of the mandibular
      body at Menton were also calculated. RESULTS: There were significant differences
      between the deviated and non-deviated sides of both groups regarding resultant
      force (symmetry group: p = 0.0372, asymmetry group: p = 0.0054), X (symmetry
      group: p < 0.0001, asymmetry group: p = 0.0001) and Y (symmetry group: p =
      0.0354, asymmetry group: p = 0.0043). For angulation, there was a significant
      difference between the deviated and non-deviated sides in the asymmetry group (p
      = 0.0095). CONCLUSION: The results of this study suggest that difference in
      stress angulation on the condyles could be associated with asymmetry in
      mandibular prognathism.

PMID- 19840286
TI  - Changes in the prevalence of asthma, eczema and hay fever in pre-pubertal
      children: a 40-year perspective.
AB  - Surveys of primary schools children in Aberdeen carried out in 1964, 1989, 1994
      and 1999 suggested a slowing of the increase in parent-reported wheeze between
      1994 and 1999. To assess whether this pattern had continued, questionnaires were
      distributed to 5712 children aged 7-12 years in the same schools in 2004. A total
      of 3271 (57.3%) completed questionnaires were returned. As in earlier surveys the
      results were divided into those for younger children (school years 3-4; age 7-9
      years) and older children (school years 5-7; age 9-12 years). Compared with 1999,
      the 2004 results showed a decrease in the proportion of children with wheeze in
      the last 3 years from 30.1% to 23.3% (P < 0.001) in the younger group and from
      27.6% to 25.1% (P = 0.052) in the older group. There was no significant change in
      the lifetime prevalence of asthma in either the younger or the older group, but
      the lifetime prevalence of eczema and hay fever increased by around 10% in both
      the younger and older groups (all P < 0.001). The differences in the time trends
      for the different conditions suggest that the causal factors for wheeze and
      asthma differ from those for other allergic diseases of childhood.

PMID- 19840287
TI  - Children with cerebral palsy: severity and trends over time.
AB  - Increasingly, more very-low-birthweight infants in the developed world are now
      expected to survive the neonatal period than was previously the case. There are
      concerns that there may be a related increase in the number of infants developing
      severe sensorimotor impairments. Pooled data from five registers contributing to
      the UK Network of Cerebral Palsy Registers, Surveys and Databases were used to
      identify patterns of motor impairment in relation to additional impairments and
      to birthweight, and to assess whether prevalence of cerebral palsy (CP) by
      birthweight and by severity of motor impairment had changed over time. Low
      birthweight infants are at greater risk of developing CP than larger-birthweight
      babies. The CP rate amongst children with birthweights <2500 g was significantly
      higher at 16 per 1000 livebirths [95% confidence interval (CI) 14.9, 16.2] than
      1.2 per 1000 livebirths [95% CI 11, 1.2] for normal-birthweight children. Despite
      being at greater risk of developing CP, smaller-birthweight babies are
      proportionately less likely to develop the most severe forms of motor impairment.
      Of those born weighing > or = 2500 g, 23% compared with 15% weighing <1000 g (P <
      0.001) were in the most severely motor impaired group. Severe motor impairment is
      associated with higher levels of additional impairments. CP rates for each motor
      impairment group in the 1990s were similar to those in the late 1970s. Rates of
      CP among infants born below normal birthweight are high but have decreased over
      time. The CP rate for infants weighing 1000-1499 g at birth decreased from around
      180 per 1000 livebirths in 1979 to around 50 per 1000 livebirths from the early
      1990s onwards.

PMID- 19840288
TI  - Trends in preterm births in Flanders, Belgium, from 1991 to 2002.
AB  - Changes in the preterm birth rate have been attributed predominantly to increases
      in multiple pregnancies, associated with advanced maternal age and assisted
      reproduction, and to obstetric intervention. We examined their contribution to
      the frequencies of preterm (<37 weeks), very preterm (<32 weeks) and severely
      preterm (<28 weeks) birth among 700 383 singleton and twin births in Flanders
      from 1991 to 2002. We examined changes across four 3-year periods (triennia) with
      confidence interval [CI] analysis and yearly incremental rates using linear and
      logistic regression analyses. Over the 12 years, twin pregnancies increased from
      1.5% to 2.0%, averaging 1.6% [95% CI 1.54, 1.66] in 1991-93 and 1.9% [95% CI
      1.81, 1.94] in 2000-02 (P < 0.001). The proportion of women aged 35 years or more
      increased from 6.8% [95% CI 6.69, 6.92] in 1991-93 to 11.3% [95% CI 11.2, 11.5]
      in 2000-02 (P < 0.001) and those aged under 20 from 1.9% [95% CI 1.81, 1.93] to
      2.3% [95% CI 2.26, 2.41] (P < 0.001). Assisted reproduction increased from 2.6%
      [95% CI 2.48, 2.62] to 4.2% [95% CI 4.11, 4.30] (P < 0.001) and obstetric
      intervention to end pregnancy from 36.2% [95% CI 36.0, 36.4] to 40.3% [95% CI
      40.1, 40.6] (P < 0.001). These increases related to an annual increase of 0.23%
      in the preterm birth rate from 5.5% [95% CI 5.4, 5.6] in 1991-93 to 7.2% [95% CI
      7.1, 7.3] in 2000-02 (P < 0.001). The proportions of very and severely preterm
      births also increased by nearly a third, but their contribution to the total
      preterm birth rate remained stable at 15% and 5%, respectively. Odds ratios for
      the increases per year were 1.035 [95% CI 1.032, 1.038] for preterm birth, 1.024
      [95% CI 1.018, 1.031] for very preterm and 1.028 [95% CI 1.017, 1.040] for
      severely preterm births after adjusting for other changes in the population.
      Overall, the data show, first, marked increases in the frequency of known
      contributors to the preterm birth rate, including twin pregnancies, advanced
      maternal age, assisted reproduction and obstetric intervention. Second, the
      preterm birth rate further increased significantly within subgroups of women with
      one or more of these characteristics. Third, the preterm birth rate also rose,
      from 4.4% [95% CI 4.2, 4.5] in 1991-93 to 5.6% [95% CI 5.5, 5.8] in 2000-02 (P <
      0.001), in women with none of these contributing factors. This indicates that
      changes in the frequency of these known predictors are insufficient to explain
      the steady increase in preterm, very preterm and severely preterm births over
      more than a decade.

PMID- 19840289
TI  - Trends in birth size and macrosomia in Queensland, Australia, from 1988 to 2005.
AB  - The objectives of this study were to explore temporal changes in birth measures
      in Queensland, Australia, and examine whether secular trends are similar to those
      in other countries. This study used data from the Queensland Perinatal Data
      Collection, including singleton livebirths (n = 831 375) from 1988 to 2005.
      Recorded birthweight (BW, g), birth length (BL, cm), gestational age (weeks),
      maternal age, ethnic origin and calculated ponderal index (PI, kg/m(3)) were
      used. Temporal trends were assessed over the intervals 1988-2005 for BW and 2001
      2005 for BW, BL and PI. Mean BW increased during the 17-year interval by
      approximately 1.9 g/year at a relatively low rate compared with reports from
      other countries. The proportion of high BW infants (> or = 4000 g) rose by 0.8%
      per year. Stratification by Indigenous status indicated that the increase in mean
      BW and prevalence of high BW was confined to non-Indigenous newborns only. The
      secular increase in BW was further modified by gestational age, and maternal age.
      The increase in BW was larger in term infants (4.2 g/year) than in preterm
      infants (1.8 g/year), and larger in infants of younger mothers than in those of
      older mothers (5.0 g/year vs. 3.1 g/year). There were no trends in mean BL and
      mean PI at birth from 2001 to 2005. In Queensland, mean BW increased moderately
      in the last 17 years, as did the proportion of high BW infants. The trend in
      rising BW remained after controlling for other perinatal characteristics. Birth
      measures per se and related trends differed by Indigenous status and warrant
      further investigation.

PMID- 19840290
TI  - Birthweight and early neonatal health: Bangladesh perspective.
AB  - It has been suggested that a birthweight limit of 2.5 kg should not be regarded
      as valid for all populations as the cut-off point of low-weight births because of
      demographic, genetic and environmental differences. Countries often choose
      alternative cut-off values for low birthweight for clinical purposes. Bangladesh
      also needs to choose a convenient cut-off value for low birthweight. A total of
      770 live singleton full-term normal newborns were included in this study by
      stratified sampling; birthweight was measured using the Detecto-type baby weight
      machine. Newborns were followed up to the end of their first week of life. For
      data collection a pretested structured questionnaire and an Apgar Score
      estimating checklist were used. Chi-square test was applied to assess the
      association of different birthweight strata and neonatal health outcomes.
      Multiple logistic regression analyses were carried out to identify the
      independent effects of different levels of birthweight on early neonatal health.
      The neonates having birthweight < or = 2 kg had a significantly higher risk of
      early neonatal mortality and morbidity than the higher level birthweight group.
      Birth asphyxia was the commonest cause of early neonatal mortality and morbidity.
      Borderline birthweight (>2 to <2.5 kg) neonates experienced the same mortality
      and morbidity rates as the normal birthweight neonates during their early
      neonatal life. Birthweight < or = 2 kg may be one of the criteria for admission
      to a neonatal intensive care unit whereas more than 2 kg may not require
      admission unless otherwise necessary.

PMID- 19840291
TI  - Relationships between birthweight and biomarkers of chronic disease in childhood:
      Aboriginal Birth Cohort Study 1987-2001.
AB  - Reports of relationships between lower birthweight and later chronic diseases are
      mainly from populations with low rates of low birthweight (LBW) and growth
      restricted births. A prospective study of an Australian Aboriginal birth cohort
      with a mean birthweight of 3050 g (SD 630), 16% LBW and 28% fetal growth
      restriction was used to examine the relationships between birthweight and
      selected biomarkers of chronic adult disease. At a mean age of 11.4 years (range
      8.9-14), the mean weight was 35.7 kg (SD 11.8) and the mean height was 143.8 cm
      (SD 10.6). Using the Centers for Disease Control and Prevention (CDC) 2000 growth
      references, weight and height-for-age z-scores were -0.8 (SD 1.4) and -0.5 (SD
      1.07) respectively and using World Health Organisation criteria, 19% of children
      were classified as underweight (weight for age Z-score <2.0). The relationships
      between birthweight and blood pressure (n = 475), total cholesterol (n = 461),
      Apolipoprotein A-1 (n = 343), Apolipoprotein B (n = 390), respiratory function
      tests (n = 427), kidney size determined by ultrasound (n = 446), urinary
      albumin/creatinine ratio (n = 420) and fasting triglycerides (n = 281), insulin
      (n = 272) and glucose (n = 279) were examined using regression models adjusted
      for sex, gestational age, current age and puberty status. In this population with
      high rates of fetal growth restriction at birth and an excess of under-nutrition
      at age 11 years we found that birthweight had a negative relationship with child
      blood pressure only, while current child weight was positively related to blood
      pressure, total cholesterol, Apolipoprotein B, respiratory function tests, kidney
      size, and fasting triglycerides, insulin and glucose.

PMID- 19840293
TI  - Previous maternal oral contraception and the risk among subsequent offspring of
      asthma diagnosis in early childhood.
AB  - Previous maternal use of the oral contraceptive pill (OCP) has been linked with
      asthma in subsequent offspring and has been implicated in the increased
      prevalence of childhood asthma in recent decades. We conducted a matched case
      control study to test the hypothesis that maternal OCP used close to conception
      is associated with asthma in the offspring, particularly in children with
      coexistent eczema. We examined maternal OCP exposure in relation to asthma in the
      offspring (n = 6730) compared with offspring with no asthma (n = 6730) further
      stratifying by eczema, age group, treatment category and gender of the offspring.
      Maternal use of OCP was classified as: no OCP use in the 2 years prior to
      conception; past OCP use within 2 years but >6 months before conception; and
      recent OCP use within 6 months of conception. The adjusted odds ratio (OR) for
      asthma in the offspring was 1.16 [95% confidence interval 1.06, 1.27] among
      mothers who were recent users of the OCP when compared with mothers who had not
      used the OCP. Past OCP use was not associated with asthma in the offspring. In
      the stratified analyses, we observed weak but statistically significant
      associations between recent maternal OCP use and asthma in the offspring among
      children: without a history of eczema (adjusted OR 1.22 [1.09, 1.36]), those aged
      < or = 3 years (adjusted OR 1.24 [1.12, 1.37]), those not on treatment for their
      asthma (adjusted OR 1.33 [1.12, 1.58]) and among females (adjusted OR 1.34 [1.13,
      1.51]). We did not find convincing evidence for a causal relationship between
      maternal OCP used close to conception and asthma in the offspring. The small
      statistically significant associations were not among children with
      characteristic features of asthma such as those with eczema and may be due to
      bias, uncontrolled confounding or chance.

PMID- 19840292
TI  - Trait anxiety in pregnant women predicts offspring birth outcomes.
AB  - The goal of our study was to characterise the relationships between trait anxiety
      symptoms of women during their pregnancies and birth outcomes of their offspring
      using a longitudinal cohort from the Maternal Health Practices and Child
      Development Project. We used the State-Trait Personality Index anxiety measure
      that is based on Spielberger's State-Trait Anxiety Inventory to measure self
      reported trait anxiety at two gestational assessments (fourth and seventh months,
      representing the first and second trimesters, respectively) and at a third
      assessment shortly after delivery (representing the third trimester).
      Demographic, social, psychological, substance use and medical factors were
      assessed prenatally, and outcomes of the 763 live, singleton births were
      determined at delivery. In regression models, trait anxiety at the second and
      third trimesters predicted lower birthweight and shorter birth length,
      controlling for confounders. Anxiety reported at the third trimester predicted
      shortened gestational age, controlling for confounders. At the first and second
      trimesters, the relationship of birthweight and birth length to maternal trait
      anxiety was only significant for severe anxiety. Women whose anxiety reached
      severe levels for at least two trimesters were significantly more likely to
      deliver offspring of lower birthweight and shorter birth length than those women
      who reported severe anxiety at none or only one of the trimesters. Additionally,
      offspring of women who experienced severe anxiety during all three trimesters had
      shorter mean gestational age than offspring of women who did not report severe
      anxiety at any trimester. Women who report chronic, severe trait anxiety are at
      the highest risk of having shorter gestations and delivering smaller babies.

PMID- 19840294
TI  - Understanding the factors associated with differences in caesarean section rates
      at hospital level: the case of Latin America.
AB  - As in many other regions of the world, caesarean section (CS) rates in Latin
      America are increasing. Studies elsewhere have shown that providing feedback to
      caregivers regarding their own performance relative to their peers can
      significantly reduce the rates. Our objectives are to calculate risk-adjusted CS
      rates for hospitals in Latin America and to identify factors associated with
      differences among risk-adjusted rates. We included 120 randomly selected
      institutions in eight countries of Latin America, representing 97 095
      pregnancies. We used random-effects models to calculate a risk-adjusted rate for
      each hospital and to identify hospitals significantly higher or lower than a
      benchmark rate. We conducted a regression analysis to identify characteristics of
      hospitals associated with differences among risk-adjusted rates. The overall CS
      rate was 35%, ranging from 0% to 85%. Risk-adjusted CS rates ranged from 11% to
      78%. Three-quarters of hospitals had risk-adjusted rates significantly above the
      previously identified benchmark of 20%. Characteristics of institutions explained
      48% of the variability among risk-adjusted rates, including being a private as
      opposed to a public institution, having some economic incentive for CS as opposed
      to no incentive, and having > or = 50 maternity beds. Strategies to halt further
      increases in CS rates and reduce rates to levels that reflect the best quality of
      care, are urgently needed worldwide. The involvement of local quality control
      departments is an essential component in achieving success. Our results can be
      used to identify institutions that can be targets for further interventions to
      reduce CS rates.

PMID- 19840295
TI  - Bronchopulmonary dysplasia and brain white matter damage in the preterm infant: a
      complex relationship.
AB  - We analysed the relationship between bronchopulmonary dysplasia (BPD) and brain
      white matter damage (WMD) in very preterm infants, adjusting for common risk
      factors and confounders. We studied a cohort of infants <32 weeks gestational age
      (GA) and <1500 g, admitted to 12 hospitals in Northern Italy in 1999-2002. The
      association between BPD and WMD was estimated by generalised estimating equations
      and conditional logistic models, adjusting for centre, GA, propensity score for
      prolonged ventilation and other potential confounders. Directed acyclic graphs
      (DAG) were used to depict the underlying causal structure and guide analysis. Of
      the 1209 infants reaching 36 weeks, 192 (15.8%) developed BPD (supplemental
      oxygen at 36 weeks) and 88 (7.3%) ultrasound-defined WMD (cystic periventricular
      leukomalacia). In crude analysis, BPD was a strong risk factor for WMD [odds
      ratio (OR) = 5.9]. With successive adjustments, the OR progressively decreased to
      3.88 when adjusting for GA, to 2.72 adding perinatal risk factors, and further
      down to 2.16 [95% confidence interval 1.1, 3.9] when ventilation was also
      adjusted for. Postnatal factors did not change the OR. Significant risk factors
      for WMD, in addition to BPD, were a low GA, a lower Apgar score, a higher illness
      severity score, ventilation and early-onset sepsis, while antenatal steroids,
      being small for GA, and surfactant were associated with a reduced risk. In
      conclusion, our data suggest that BPD is associated with an increased risk of
      WMD; most of the effect is due to shared risk factors and causal pathways. DAGs
      helped clarify the complex confounding of this scenario.

PMID- 19840297
TI  - Self-selection and bias in a large prospective pregnancy cohort in Norway.
AB  - Self-selection in epidemiological studies may introduce selection bias and
      influence the validity of study results. To evaluate potential bias due to self
      selection in a large prospective pregnancy cohort in Norway, the authors studied
      differences in prevalence estimates and association measures between study
      participants and all women giving birth in Norway. Women who agreed to
      participate in the Norwegian Mother and Child Cohort Study (43.5% of invited; n =
      73 579) were compared with all women giving birth in Norway (n = 398 849) using
      data from the population-based Medical Birth Registry of Norway in 2000-2006.
      Bias in the prevalence of 23 exposure and outcome variables was measured as the
      ratio of relative frequencies, whereas bias in exposure-outcome associations of
      eight relationships was measured as the ratio of odds ratios. Statistically
      significant relative differences in prevalence estimates between the cohort
      participants and the total population were found for all variables, except for
      maternal epilepsy, chronic hypertension and pre-eclampsia. There was a strong
      under-representation of the youngest women (<25 years), those living alone,
      mothers with more than two previous births and with previous stillbirths
      (relative deviation 30-45%). In addition, smokers, women with stillbirths and
      neonatal death were markedly under-represented in the cohort (relative deviation
      22-43%), while multivitamin and folic acid supplement users were over-represented
      (relative deviation 31-43%). Despite this, no statistically relative differences
      in association measures were found between participants and the total population
      regarding the eight exposure-outcome associations. Using data from the Medical
      Birth Registry of Norway, this study suggests that prevalence estimates of
      exposures and outcomes, but not estimates of exposure-outcome associations are
      biased due to self-selection in the Norwegian Mother and Child Cohort Study.

PMID- 19840296
TI  - Breast feeding very-low-birthweight infants at discharge: a multicentre study
      using WHO definitions.
AB  - Human milk has several advantages in the nutrition of very-low-birthweight (VLBW)
      infants. However, there are limited data on breast feeding (BF) in neonatal
      intensive care units (NICU). The aim of this study was to identify a practical
      definition of BF rate in VLBW infants and to test its applicability and
      reproducibility in Italian NICUs. The study population included all VLBW infants
      discharged from 12 level 3 NICUs, over a 12-month period. Type of feeding was
      recorded according to the World Health Organisation (WHO) definition, with a 72-h
      recall period. We enrolled 594 VLBW infants. Mean birthweight was 1105 g (SD:
      267), mean gestational age was 29.2 weeks (SD: 2.7) and mean length of stay in
      NICUs was 62.5 days (SD: 56.5). At discharge, 30.5% of VLBW infants were
      exclusively breast fed, 0.2% were predominantly breast fed, 23.8% were on
      complementary feeding and 45.5% were exclusively formula fed. A wide variability
      in BF rates was seen between centres. Among exclusively breast-fed VLBW infants,
      only 10% sucked directly and exclusively at the breast. WHO definitions can be
      used to assess type of feeding at discharge from NICUs. We speculate that common
      feeding definitions may allow both comparisons among different NICUs and ratings
      of quality improvement programmes.

PMID- 19840298
TI  - Treatment of severe vernal keratoconjunctivitis with 1% topical cyclosporine in
      an Italian cohort of 197 children.
AB  - The purpose of our study was to verify the efficacy of prolonged cycles of 1%
      topical cyclosporine in improving severe form of vernal keratoconjunctivitis
      (VKC) in childhood and investigate for factors affecting the response to therapy.
      We conducted an open trial involving 197 children with severe VKC, who received
      topical cyclosporine 1% for 4 months. Ocular subjective symptoms (SS) and
      objective signs (OS) were scored in all children at entry, 2 wks and 4 months.
      Skin prick tests and microscope endothelial cells evaluation were also performed;
      serum immunoglobulin E and cyclosporine levels were assessed. The mean score
      values for severity of SS and OS were significantly decreased after 2 wks and 4
      months, compared with those at entry (p < 0.001) in all children. Cyclosporine
      serum levels were neither detectable at the end of therapy, nor were endothelial
      corneal cells damaged. Patients who started the therapy at the beginning of the
      disease and/or received long-term regimen of treatment with cyclosporine had a
      faster improvement of ocular signs and symptoms, compared with all other
      patients. Our findings suggest that 1% cyclosporine concentration administrated
      topically at the beginning of the disease and for a long-term period might be the
      most effective treatment to control symptoms and local inflammation in severe
      forms of VKC in childhood.

PMID- 19840299
TI  - DNA damage and glutathione level in children with asthma bronchiale: effect of
      antiasthmatic therapy.
AB  - When the production of reactive oxygen species (ROS) exceeds the capacity of
      antioxidant defences, a condition known as oxidative stress occurs and it has
      been implicated in many pathological conditions including asthma. Interaction of
      ROS with DNA may result in mutagenic oxidative base modifications such as 8
      hydroxydeoxyguanosine (8-oxo-dGuo) and DNA strand breaks. Reduced glutathione
      (GSH) serves as a powerful antioxidant against harmful effects of ROS. The aim of
      this study was to describe DNA damage as level of DNA strand breaks and
      formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites, which reflects
      oxidative DNA damage and GSH level in children with mild-to-moderate persistent
      asthma; and to examine the effect of antiasthmatic therapy on these DNA damage
      parameters and GSH level. Before and after 8 wk of antiasthmatic therapy blood
      samples were taken, DNA strand breaks and Fpg-sensitive sites in peripheral
      leukocytes were determined by comet assay, GSH level of whole blood was measured
      by spectrophotometric method. DNA strand breaks and Fpg-sensitive sites in the
      asthma group were found to be increased as compared with control group. GSH level
      in the asthma group was not significantly different from those in the control
      group. Levels of strand breaks, Fpg-sensitive sites and GSH were found to be
      decreased in the asthma group after the treatment. In conclusion, oxidative DNA
      damage (strand breaks and Fpg-sensitive sites) is at a high level in children
      with asthma. DNA damage parameters and GSH level were found to be decreased after
      therapy. Our findings imply that antiasthmatic therapy including
      glucocorticosteroids not only controls asthma but also decreases mutation risk in
      children with asthma bronchiale.

PMID- 19840300
TI  - Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis,
      Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind,
      randomized, placebo-controlled trial.
AB  - Controversy exists regarding the preventive effect of probiotics on the
      development of eczema or atopic dermatitis. We investigated whether
      supplementation of probiotics prevents the development of eczema in infants at
      high risk. In a randomized, double-blind, placebo-controlled trial, 112 pregnant
      women with a family history of allergic diseases received a once-daily
      supplement, either a mixture of Bifidobacterium bifidum BGN4, B. lactis AD011,
      and Lactobacillus acidophilus AD031, or placebo, starting at 4-8 wks before
      delivery and continuing until 6 months after delivery. Infants were exclusively
      breast-fed during the first 3 months, and were subsequently fed with breastmilk
      or cow's milk formula from 4 to 6 months of age. Clinical symptoms of the infants
      were monitored until 1 yr of age, when the total and specific IgE against common
      food allergens were measured. A total of 68 infants completed the study. The
      prevalence of eczema at 1 yr in the probiotic group was significantly lower than
      in the placebo group (18.2% vs. 40.0%, p=0.048). The cumulative incidence of
      eczema during the first 12 months was reduced significantly in probiotic group
      (36.4% vs. 62.9%, p=0.029); however, there was no difference in serum total IgE
      level or the sensitization against food allergens between the two groups.
      Prenatal and postnatal supplementation with a mixture of B. bifidum BGN4, B.
      lactis AD011, and L. acidophilus AD031 is an effective approach in preventing the
      development of eczema in infants at high risk of allergy during the first year of
      life.

PMID- 19840301
TI  - Chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne,
      pustulosis, hyperostosis, and osteitis (SAPHO) syndrome with associated
      neutrophilic dermatoses: a report of seven cases and review of the literature.
AB  - A growing body of literature has identified the association between neutrophilic
      dermatoses and multifocal, aseptic bone lesions in children, termed chronic
      recurrent multifocal osteomyelitis (CRMO). Classically, patients present with
      swelling, pain, and impaired mobility of the affected area, with skin lesions
      developing concurrently or in the future. Bone biopsy reveals inflammatory
      changes consistent with infectious osteomyelitis, but cultures and histologic
      staining invariably fail to identify an infectious source. Patients are
      refractory to antibiotic therapy, but dramatically respond to systemic steroids
      and may need to be maintained on low-dose steroids to prevent relapse. Numerous
      authors have suggested that CRMO and synovitis, acne, pustulosis, hyperostosis,
      osteitis (SAPHO) syndrome lie along the same clinical spectrum. In fact some
      believe that CRMO is the pediatric presentation of SAPHO. The two syndromes share
      numerous characteristics, including osteitis, a unifocal or multifocal
      presentation, hyperostosis, and pustulosis, which all occur in a generally
      healthy individual. Our seven patients, five of whom were diagnosed with CRMO,
      and two of whom were diagnosed with SAPHO syndrome further strengthen the idea
      that CRMO and SAPHO syndrome do indeed lie along the same clinical spectrum. In
      addition, we include two rare cases of pediatric Sweet's syndrome with evidence
      of pathergy.

PMID- 19840302
TI  - Clinical demonstration of skin mildness and suitability for sensitive infant skin
      of a new baby wipe.
AB  - BACKGROUND: A cleansing baby wipe with sufficient pH buffering capacity may help
      to restore the pH balance of skin following exposure to urine and feces in the
      diaper environment and maintain skin health. OBJECTIVE: To evaluate the skin
      effects of a novel baby wipe formulation with increased pH buffering. SUBJECTS
      AND METHODS: A series of clinical studies was designed and conducted to evaluate
      the skin effects of the new baby wipe, including a 21-day cumulative skin
      irritation patch study in adults (n = 31), a 4-week study in babies with
      medically confirmed atopic dermatitis (n = 32), a 2-week study comparing skin pH
      of babies (n = 15) following use of wipes compared with water and wash cloth, a
      series of clinical skin pH measurements following fecal exposure and subsequent
      cleaning with different products (n = 50) and a study evaluating comfort of
      product application on irritated skin (n = 31). RESULTS: The wipes formulation
      was well-tolerated, even in babies with atopic dermatitis, and was more
      comfortable versus water and washcloth. Increased buffering capacity of a wet
      wipes lotion helps to maintain a physiologically balanced skin pH value in the
      diaper region.

PMID- 19840303
TI  - Premenarchal vulvar ulceration: is chronic irritation a causative factor?
AB  - OBJECTIVE: To study the common features of the young girls with vulvar
      ulcerations, and to help guide physicians caring for girls with this unusual
      condition. METHODS: In this retrospective study, ten patients who developed
      vulvar ulcerations and denied any kind of sexual contact or sexual abuse were
      identified. Patient information was collated from detailed history, physical, and
      laboratory examinations including age, menarchal status, type of clothing worn,
      whether history of oral aphthosis or previous vulvar ulcers had occurred,
      symptoms at the time of presentation, description of ulcer, laboratory studies
      including serologies, blood count, erythrocyte sedimentation rate, C-reactive
      protein, and biopsy results. RESULTS: Despite multiple evaluations, no patient
      had a specific medical cause identified to account for their vulvar ulcerations.
      None were diagnosed with Behcet's syndrome. Seven had bilateral vulvar
      ulcerations, which we attribute to the practice of wearing tightly fitted pants
      or polyester underwear frequently. No recurrences were documented in 6 months
      follow-up. CONCLUSION: Girls with vulvar ulcerations who have deny being sexually
      active should be thoroughly evaluated for infections, Behcet's disease, and other
      health problems, but, in addition, should be questioned about use of tight
      fitting clothing in the perineal area. We hypothesize that chronic irritation
      because of tight clothing may play a role in causing vulvar ulcerations in this
      setting.

PMID- 19840304
TI  - Knowledge and perception of melanocytic nevi and sunburn in young children.
AB  - BACKGROUND/OBJECTIVES: Understanding the public's perception of nevi and sunburn
      is crucial to melanoma prevention efforts. METHODS: We investigated the knowledge
      and perception of melanocytic nevi and sunburns in 77 children 6 to 10 years old
      (mean 8.2) in two elementary schools in Styria, Austria. The children were
      interviewed by specially trained psychologists about the number of their moles
      and how they felt having them. Additionally questions about sunburn history and
      sunburn perception were asked. The spontaneous answers of the children were
      recorded, there were no pregiven answers. Afterwards the children were examined
      by dermatologists clinically and with dermatoscopes. RESULTS: The 96% of the
      children could describe a nevus (the term "mole" was translated to "nevus") and
      91% did not feel bothered about theirs. Only 26% had noted the appearance of new
      nevi within the last year. The 67% of all children had at least one sunburn and
      remembered the clinical features. The 20% of the children knew that sunburns
      could provoke skin cancer. All children felt comfortable during the clinical and
      dermatoscopic examination. CONCLUSION: Children aged from 6 to 10 years know
      exactly why they had suffered from sunburn, can describe the sunburn and how to
      avoid it. They do not feel bothered by their nevi and are alert to the appearance
      of new nevi.

PMID- 19840305
TI  - Corticosteroids' effect on the height of atopic dermatitis patients: a controlled
      questionnaire study.
AB  - To investigate if children treated with topical corticosteroids have a
      significantly shorter height than the height of children not treated with
      corticosteroids and to see if corticosteroids affect the ability for treated
      children to meet growth potential defined as midparental height. Parents of
      patients attending the UNC's Dermatology clinic completed the survey. The
      patient's height and siblings' heights were measured by staff. Parents' heights
      were self reported as were the child's diagnosis of atopic dermatitis, and
      duration of use of corticosteroids. The patient's height was standardized using
      CDC charts. Additionally, the midparental height was calculated and standardized.
      The difference between present and predicted standardized heights was calculated;
      151 surveys yielded data on 83 girls and 63 boys (ages 2-21 yrs). The standing
      height and the difference in standing height and midparental scores were not
      significantly different among: (i) children with and without atopic dermatitis;
      and (ii) children treated and not treated with corticosteroids. The overall
      height of children examined in this survey who were treated with topical
      corticosteroids appears to be unaffected.

PMID- 19840306
TI  - Knowledge, attitudes, and behaviors of elementary school students regarding sun
      exposure and skin cancer.
AB  - The aim of this study was to assess baseline knowledge of skin cancer, sun
      protection practices, and perceptions of tanning among third through fifth grade
      elementary students in Florida. A total of 4,002 students in nineteen elementary
      schools in Palm Beach County, Florida were surveyed. SunSmart America curriculum
      pretest responses were the main outcome measures. Overall students' knowledge
      using a students' mean knowledge scale scores of skin cancer and sun protection
      were low (<40% of questions answered correctly) and was found to increase with
      increasing grade level (p < 0.01). Boys more frequently reported spending greater
      than 2 hours in the sun when compared with girls (p < 0.01). Girls, however, were
      more likely to try and get a tan most of the time or always when compared with
      boys (p = 0.02). Non-Hispanic White students (51.3%) more frequently reported use
      of SPF 15 or greater sunscreen "most of the time or always" compared with
      Hispanic (35.3%) and non-Hispanic Black (13.4%) students (p < 0.01). Elementary
      aged students in south Florida have limited knowledge about sun safety, despite
      spending considerable amount of time in the sun. Sun safe behavior is associated
      with gender and ethnicity. The findings provide empirical support for the need of
      a school-based educational intervention.

PMID- 19840307
TI  - Retrospective analysis of 32 pediatric patients with anticonvulsant
      hypersensitivity syndrome (ACHSS).
AB  - OBJECTIVE: To review 32 pediatric patients with anticonvulsant hypersensitivity
      syndrome. DESIGN: Retrospectively, data and photographs were collected on 32
      patients who had been diagnosed with anticonvulsant hypersensitivity syndrome.
      SETTING: The sections of dermatology at Children's Memorial Hospital in Chicago,
      Illinois, and Children's Mercy Hospitals and Clinics in Kansas City, Missouri.
      MAIN OUTCOME MEASURES: Presentation, implicated medications, laboratory
      evaluations, complications, treatment and outcome. RESULTS: The mean age of all
      patients with anticonvulsant hypersensitivity syndrome (ACHSS) was 8.9 years. The
      mean duration of anticonvulsant therapy before onset of symptoms was 3 weeks.
      Phenytoin, carbamazepine, and phenobarbital were the most commonly implicated
      medications. Lamotrigine, oxcarbamazepine, and primidone were implicated in some
      of our patients. Fever and rash were seen in all patients, while lymphadenopathy
      was found in 84.4% of patients. Hematologic abnormalities were seen in 93.8% and
      hepatic involvement was seen in 90.4% of cases, representing the two most
      commonly involved systems. Atypical lymphocytosis and eosinophilia was seen in
      72% and 56% of patients, respectively. Renal and pulmonary involvement were each
      seen in 15.6% of cases. Systemic steroids were used in 59.4% of ACHSS patients;
      16% of patients received intravenous immunoglobulin. No deaths were reported in
      our group of pediatric patients. CONCLUSIONS: The ACHSS is a distinct clinical
      entity which may occur in pediatric patients treated with anticonvulsants, and
      may have potentially life-threatening consequences. Involvement of multiple organ
      systems, including the hematologic, hepatic, renal, and pulmonary systems was
      common. Treatment varied widely, but ranged from supportive care to systemic
      corticosteroids.

PMID- 19840308
TI  - 308-nm excimer laser for the treatment of alopecia areata in children.
AB  - Alopecia areata (AA) is a common skin disease which is characterized by
      nonscarring localized or diffused hair loss. In this study we assessed the
      efficacy of 308-nm Excimer laser in the treatment of alopecia areata in children.
      A total of 9 children with 30 recalcitrant patches alopecia areata and two
      children with alopecia areata totalis were enrolled in this study which included
      seven male and four female patients, aged between 4 and 14 years and the
      durations of their disease were between 7 and 25 months. All of these patients
      had more than one lesion of alopecia areata and at least one of them was left as
      a control for comparison. The lesions were treated with the 308-nm Excimer laser
      twice a week for a period of 12 weeks. Regrowth of hair was observed in 18 (60%)
      alopecia patches in the scalp, while there was no response in the control patches
      and over the extremities. Only four patients with scalp lesions showed a
      recurrence of alopecia after 6 months post laser therapy. So, 308-nm Excimer
      laser is considered an effective safe therapeutic option for patchy alopecia
      areata in children.

PMID- 19840309
TI  - Twice-daily versus once-daily applications of pimecrolimus cream 1% for the
      prevention of disease relapse in pediatric patients with atopic dermatitis.
AB  - The aim of this study is to compare twice-daily and once-daily applications of
      pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric
      patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years,
      with mild-to-severe atopic dermatitis. The patients were initially treated with
      twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks
      (open-label period). Those who achieved a decrease of at least 1 point in the
      Investigator's Global Assessment score were then randomized to double-blind
      treatment with pimecrolimus cream 1% either twice daily or once daily for up to
      16 weeks. Study medication was discontinued during periods of disease remission
      (Investigator's Global Assessment = 0). The primary efficacy end point of the
      double-blind phase was disease relapse (worsening requiring topical
      corticosteroids or additional/alternative therapy and confirmed by Investigator's
      Global Assessment score > or = 3 and pruritus score > or = 2). Of the 300
      patients enrolled in the study, 268 were randomized to treatment with
      pimecrolimus cream 1% either twice daily or once daily (n = 134 in each group).
      The relapse rate was lower in the twice-daily dose group (9.9%) than that in the
      once-daily dose group (14.7%), but analysis of the time to disease relapse, using
      a Cox proportional model to adjust for confounding variables, did not show a
      statistically significant difference between treatment arms (hazard ratio: 0.64;
      95% CI: 0.31-1.30). Treatment of active atopic dermatitis lesions with
      pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was
      sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in
      pediatric patients.

PMID- 19840310
TI  - Difficult-to-control bleeding.
AB  - A 12-year-old girl presented for excision of a nevus sebaceous of the scalp. The
      surgery was complicated by unexpected difficult-to-control bleeding in the
      operating room. Numerous attempts to obtain hemostasis were unsuccessful
      including the use of local anesthetic containing epinephrine, direct pressure,
      wall suction, monopolar electrocautery using different tip sizes, sponge sticks,
      and Gelfoam. Finally bleeding was contained using a suction-electocautery unit
      frequently used by otolaryngology. This article reviews the usual causes of
      unexpected bleeding in the pediatric population and both familiar and unfamiliar
      methods to control operative bleeding.

PMID- 19840311
TI  - Neonatal sporotrichosis.
AB  - Sporotrichosis is caused by the dimorphic fungus, Sporothrix schenckii.
      Classically, infection occurs after implantation of the organism into the skin by
      abrasion of a puncture wound by contaminated thorns, hay, or sphagnum moss. Cats
      are also a commonly recognized source of sporotrichosis. In children, fixed
      cutaneous lesions are more common than lymphocutaneous lesions, and the face is a
      frequent location for infection. We present a neonate with a fixed cutaneous
      facial lesion and both pre-auricular and cervical lymphadenopathy who developed
      signs of infection at 3 weeks of age. This patient is currently the youngest
      reported case of sporotrichosis in the literature. The patient's family denied
      any trauma and denied contact with flowers, gardens, and cats; thus, the source
      of infection remains unknown.

PMID- 19840312
TI  - Acquired acral lipodystrophy in a 6-year-old girl.
AB  - We report a case of partial lipodystrophy in a 6-year-old girl with normal lipid
      and glucose metabolism and no family history for similar disorders. The clinical
      presentation, the laboratory investigations and the natural history in our
      patient do not match the diagnostic criteria for any of the established
      lipodystrophy subsets.

PMID- 19840313
TI  - Childhood lichen planus pemphigoides: a case report and review of the literature.
AB  - Lichen planus pemphigoides is a rare autoimmune blistering disease that is
      characterized by evolution of vesico-bullous skin lesions in patients with active
      lichen planus. We describe a case of lichen planus pemphigoides in a 6-year-old
      boy and review the clinical and immunopathologic features of all reported cases
      of pediatric lichen planus pemphigoides. The mean age at onset of childhood
      lichen planus pemphigoides is 12 years with a male to female ratio of 3:1 and a
      mean lag-time between lichen planus and the development of lichen planus
      pemphigoides of 7.9 weeks. Vesiculo-bullous lesions were found on the extremities
      in all patients and there was palmoplantar involvement in about half of the
      cases. Direct and indirect immunofluorescence features were similar to those
      reported in adults. One patient had Western immunoblot data revealing antigens of
      180, 230, and 200 kDa. Immunoelectron microscopy in two cases showed localization
      of immune deposition different from that in bullous pemphigoid. We found that
      topical corticosteroids or oral dapsone caused resolution of lichen planus
      pemphigoides without known relapse of blistering in four cases, suggesting that
      it might be possible to reserve oral corticosteroids as a second line of therapy
      in children with lichen planus pemphigoides.

PMID- 19840314
TI  - Successful treatment of Candida albicans septicemia in a preterm infant with
      severe congenital ichthyosis (Harlequin baby).
AB  - Candida infections are a major cause of fungal septicemia in neonates and are
      associated with marked morbidity and mortality. Despite the spectrum of
      antifungal drugs being dramatically extended during the last decade, invasive
      fungal infections remain a serious challenge for neonatologists. Amphotericin B
      and its lipid formulations are the drugs of choice for the treatment of systemic
      candidiasis in neonates. The combination of antifungal drugs with different sites
      of action, like caspofungin and amphotericin B, may improve antifungal efficacy.
      Severe congenital ichthyosis often leads to death within the neonatal period.
      Main causes of death are dehydration, electrolyte disturbances, and respiratory
      or systemic infections. We report the case of a preterm infant with severe
      congenital ichthyosis and sepsis caused by Candida albicans. The infection did
      not improve despite proper liposomal amphotericin B treatment. After addition of
      caspofungin, the baby recovered. To our best knowledge, a case of a preterm
      infant suffering from severe congenital ichthyosis and Candida albicans sepsis,
      who survived, has not been previously described.

PMID- 19840315
TI  - Gadolinium-associated nephrogenic systemic fibrosis in a 9-year-old boy.
AB  - We describe a 9-year-old boy on chronic hemodialysis who presented with
      hyperpigmented, tightly bound-down, indurated plaques of his bilateral lower
      extremities. Pertinent history included a recent series of magnetic resonance
      imaging tests utilizing gadolinium-based contrast media. Histopathology showed
      widened septae with increased fibroblasts and collagen in the subcutis consistent
      with nephrogenic systemic fibrosis. Nephrogenic systemic fibrosis is a unique
      fibrosing disorder characterized by skin thickening of the extremities and trunk,
      resembling that seen in systemic sclerosis. The majority of cases have been
      reported in dialysis or renal transplant patients. This case of nephrogenic
      systemic fibrosis in a young child is presented to raise awareness in the
      pediatric community of nephrogenic systemic fibrosis and of gadolinium contrast
      being a possible trigger.

PMID- 19840316
TI  - An 18-year-old male with severe bilateral cataracts and atopic dermatitis--a case
      report and review of the literature.

PMID- 19840317
TI  - Nodulosis in systemic onset juvenile idiopathic arthritis: an uncommon event with
      spontaneous resolution.
AB  - Accelerated nodulosis is a rare complication of methotrexate therapy in juvenile
      idiopathic arthritis. When nodulosis does occur in patients with juvenile
      idiopathic arthritis on methotrexate, it is almost always seen in patients with
      polyarthritis with rheumatoid factor seropositivity, but only occasionally in
      polyarthritis patients who are rheumatoid factor negative. It has been described
      previously in only one patient with systemic arthritis. In this study, we
      describe three patients with systemic arthritis, all of whom developed nodulosis
      while receiving methotrexate. Interestingly, it was not necessary to discontinue
      methotrexate in any of these patients. In fact, methotrexate dose was escalated
      without consequences and with complete resolution of nodules. This observation
      suggests that nodulosis occurring in patients with systemic arthritis already on
      methotrexate may not be because of methotrexate itself, but may be a component of
      the disease process. The other likely possibility given the fact that nodulosis
      occurs with other immunomodulatory agents and is not specifically related to
      methotrexate is that immunomodulatory agents in general precipitate the
      development of nodulosis. Thus, we propose that the new terminology
      "immunomodulatory agents induced nodulosis" rather than "methotrexate-induced
      nodulosis" be used in the literature.

PMID- 19840318
TI  - Sporotrichoid aspergillosis in an immunocompromised child: a case report and
      review of the literature.
AB  - Primary cutaneous aspergillosis is an uncommon, opportunistic infection. Atypical
      presentations have recently emerged with the expanding range of primary and
      acquired diseases that cause immunosuppression. Primary cutaneous aspergillosis
      may invade the deep lymphatic structures and present in a sporotrichoid pattern.
      In pediatric patients with an otherwise normal previous medical history, primary
      cutaneous aspergillosis should raise the suspicion of an immunodeficiency and
      prompt referral to immunology and infectious disease specialists should be made.
      Early diagnosis and management of primary cutaneous aspergillosis prevents
      invasive aspergillosis, minimizing morbidity and mortality in the
      immunocompromised patients.

PMID- 19840319
TI  - Factitious purpura in a 10-year-old girl.
AB  - We describe a 10-year-old girl who presented with bizarre purpura. Both
      congenital and autoimmune hemorrhagic disorders were excluded based on her past
      medical history and physical and laboratory findings. Child abuse was also ruled
      out as purpura continued to develop after child-family separation. Histologic
      examination of the skin lesions revealed disruption of collagen fiber bundles.
      This finding indicated application of external force, leading to a definitive
      diagnosis of factitious purpura. Although it is very rare in school-age children,
      the diagnosis of factitious purpura should be included in the differential
      diagnosis of purpura in children. Histologic analysis of skin biopsies may aid in
      establishing the diagnosis.

PMID- 19840320
TI  - Aeromonas hydrophila folliculitis associated with an inflatable swimming pool:
      mimicking Pseudomonas aeruginosa infection.
AB  - Aeromonas species are ubiquitous, facultative, anaerobic, gram-negative
      flagellated rods, mainly found in aquatic ecosystems worldwide. Skin and soft
      tissue infections, including cellulitis and wound infections, are the second most
      frequent location of isolations of Aeromonas spp. in clinical samples, after the
      gastrointestinal tract. All three major Aeromonas species (A. hydrophila, A.
      caviae, and A. veroni biotype sobria) have been associated with wound infections,
      but A. hydrophila predominates. Typically, infection occurs after trauma and
      subsequent exposure to contaminated fresh water or soil. However, Aeromonas
      folliculitis has been rarely reported. We report the first two pediatric cases of
      Aeromonas hydrophila folliculitis associated with the use of recreational water
      facilities that clinically and epidemiologically mimic Pseudomonas folliculitis.
      Clinical and microbiological studies may be necessary to clarify the role of
      Aeromonas spp. in this newly-reported infection.

PMID- 19840321
TI  - Metastatic cutaneous Crohn's disease in children: case report and review of the
      literature.
AB  - Metastatic cutaneous Crohn's disease is a rare complication of Crohn's disease,
      especially in the pediatric population, and can present a diagnostic dilemma.
      Most of the reported cases of metastatic cutaneous Crohn's disease in childhood
      have concurrent gastrointestinal symptoms and/or perianal disease to aid in the
      diagnosis. We present a case of a 13 1/2-year-old girl whose initial symptom of
      Crohn's disease was asymptomatic labial swelling. An overview of metastatic
      cutaneous Crohn's disease in childhood is also provided.

PMID- 19840322
TI  - Propranolol treatment for hemangioma of infancy: risks and recommendations.
AB  - Hemangioma of infancy is a condition that may be associated with significant
      morbidity. While evidence most supports the use of corticosteroids, there is no
      well-defined or Federal Drug Administration (FDA)-approved systemic therapy for
      hemangioma of infancy. All currently used treatments have significant risks.
      Dramatic improvement of complicated hemangioma of infancy to propranolol was
      recently reported, but details for initiating therapy, monitoring, and potential
      risks were not included. We present two infants treated with propranolol, who
      suffered complications and propose a treatment protocol to minimize potential
      adverse events.

PMID- 19840323
TI  - Keratotic papular eruption in a teenager.

PMID- 19840324
TI  - Cerebriform lesion over scalp with alopecia.

PMID- 19840325
TI  - A crusted, friable papule on the scalp of a 17-month-old boy.

PMID- 19840326
TI  - AEC syndrome caused by a novel p63 mutation and demonstrating erythroderma
      followed by extensive depigmentation.
AB  - We present an infant with AEC syndrome due to a novel TP63 mutation (F552S), who
      demonstrated neonatal erythroderma followed by extensive depigmentation. We are
      unaware of previous reports highlighting the extensive depigmentation present in
      our patient.

PMID- 19840327
TI  - Mammary skin tag in a 2-year-old girl: a long-lasting adnexal polyp of neonatal
      skin?
AB  - We describe the case of a 2-year-old girl showing a pedunculated lesion on the
      areola of the nipple since birth. Clinical and histological features were
      consistent with an adnexal polyp of neonatal skin observed beyond the neonatal
      period.

PMID- 19840328
TI  - Allergic contact granuloma: an uncommon reaction to pierced earrings in a child.
AB  - Allergic contact dermatitis associated with pierced earrings typically presents
      as erythematous patches and plaques, with prominent spongiosis histologically.
      The most common inciting metal is nickel. Allergic contact granulomatous
      reactions to pierced earrings are rare, and are often more nodular in appearance
      and associated with metals other than nickel. We hereby report the first case of
      allergic contact granulomas associated with pierced earrings in a child.

PMID- 19840329
TI  - Solitary cutaneous leiomyoma in an infant.
AB  - This report describes a case of leiomyoma of the ankle occurring at an unusual
      age. A 5-month-old girl presented with an asymptomatic nodule on her left ankle.

PMID- 19840330
TI  - A severe case of acute generalized exanthematous pustulosis (AGEP) in a child
      after the administration of amoxicillin-clavulanic acid: brief report.

PMID- 19840331
TI  - Neonatal frostbite with gangrene of toes.
AB  - Gangrene of the extremities in the neonatal period is rare. Etiology is not
      identified in most cases and management is usually conservative. We describe an
      unusual case of an abandoned neonate with marked hypothermia, who was brought to
      us with gangrene of toes, during a severe winter. The toes auto-amputated after 2
      weeks. A negative sepsis screen, normal Doppler study, and absence of evidence of
      hypercoagulable state prompted us to incriminate localized cold injury
      (frostbite) as the probable cause of gangrene in this newborn infant.

PMID- 19840332
TI  - Linear nodular collagenoma--successful treatment with intralesional triamcinolone
      acetonide.
AB  - A 17-year-old boy presented with papules and nodules arranged linearly on the
      neck and on the forehead. A diagnosis of collagenoma was made. Intralesional
      injection of triamcinolone acetonide resulted in marked effacement of the
      lesions.

PMID- 19840333
TI  - Adverse effects of a mole removal cream.
AB  - Mole removal creams available over the Internet pose potential dangers to
      unsuspecting patients. We report a case of keloid development following the
      application of such a product.

PMID- 19840334
TI  - Vulvar pyoderma gangrenosum in a child.
AB  - We present a case of a 10-year-old girl with a diagnosis of vulvar pyoderma
      gangrenosum. Intravenous methylprednisolone was started and on tapering the
      steroid regimen, the lesion showed significant enlargement and purulent discharge
      without any remission of fever and inflammatory activity, so she was treated with
      oral cyclosporin A in combination with low-dose steroid. A response to treatment
      was achieved after 2 weeks and clinical and laboratory follow-up at 12 months did
      not show any disease relapse or inflammation.

PMID- 19840335
TI  - Ascher syndrome: a case report.
AB  - Ascher syndrome is a rare disease described by Ascher, an ophthalmologist from
      Prague, in 1920. We report a case of an 8-year-old child, who presented with
      recalcitrant recurrent swelling of bilateral upper eyelids, probably a forme
      fruste of Ascher syndrome.

PMID- 19840336
TI  - Cutaneous Rosai-Dorfman disease: presenting as massive bilateral eyelid swelling.
AB  - Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder, which
      commonly affects the lymph nodes. Cutaneous Rosai-Dorfman disease is a rare form
      of Rosai-Dorfman disease limited to the skin. We report a case of cutaneous Rosai
      Dorfman presenting with bilateral eyelid swelling in a child.

PMID- 19840337
TI  - Lyme disease as a cause of acropapular dermatitis of childhood.
AB  - Acropapular dermatitis of childhood is a symmetric self-limited papulovesicular
      exanthem that classically occurs on the cheeks, extensor extremities, and
      buttocks in young children. The eruption of acropapular dermatitis of childhood
      represents a reaction to a variety of infections usually of viral origin. We
      present a child with typical findings of acropapular dermatitis of childhood
      whose serologic workup revealed an acute Lyme infection.

PMID- 19840338
TI  - Angiomatoid fibrous histiocytoma in a six-year-old child.
AB  - We report a case of AFH presenting as an asymptomatic subcutaneous nodule on the
      arm of a 6-year-old boy. AFH is a fibrohistiocytic tumor of intermediate
      malignancy. Predominantly seen in children and young adults, AFH presents as a
      deep dermal or subcutaneous nodule usually on the extremities. The histology is
      characterized by a fibrous capsule, surrounding lymphocytic infiltrate and blood
      filled cystic spaces lined by flattened tumor cells. AFH cells express desmin,
      epithelial membrane antigen, and CD 68 in over 60% of cases; they are negative
      for myogenin, MYOD1, and endothelial markers. Rate of local recurrence is 2% to
      20%. The metastatic rate is 1%. Management is with wide surgical excision and
      careful follow-up.

PMID- 19840339
TI  - Protein losing enteropathy in severe atopic dermatitis in an exclusively breast
      fed infant.
AB  - We first report a case of protein losing enteropathy in severe atopic dermatitis
      in an exclusively breast-fed 5-month-old infant. Protein losing enteropathy was
      confirmed by fecal alpha1-antitrypsin clearance test and imaged successfully by
      99mTc-human serum albumin scintigraphy. The present case highlights that protein
      losing enteropathy in severe infantile atopic dermatitis is being a topic of
      concern and also an issue even in exclusive breast feeding patients.

PMID- 19840340
TI  - Tongue granulomatous lesion caused by mandibular primary incisors eruption.
AB  - The aim of this report was to present a case of granulomatous lesion on the
      ventral surface of the tongue in a 9-month-old, healthy, infant girl, caused by
      the habit of scraping the tongue on mandibular central incisors. Clinical
      treatment consisted of manual smoothing of the sharp edges of both incisors and
      excision of the 2-cm pediculate ulcerative granulomatous mass localized on the
      ventral surface of the tongue. After 3 weeks, the child could be properly fed and
      a complete healing of the lesion was observed.

PMID- 19840341
TI  - Propranolol for infantile hemangiomas: promise, peril, pathogenesis.

PMID- 19840344
TI  - A review of the effects of growth hormone changes on symptoms of frailty in the
      elderly with chronic kidney disease.
AB  - The incidence and prevalence of chronic kidney disease (CKD) is increasing
      worldwide, especially in the elderly. Recently, functional impairment and frailty
      have been recognized as factors affecting the quality of life, and outcomes in
      elderly patients with CKD and therapeutic interventions to improve function and
      reduce frailty are therefore being considered. Growth hormone (GH) levels
      decrease with age and GH actions are impaired in CKD patients. GH stimulates
      protein synthesis, bone, and glucose metabolism, and affects body composition by
      reducing body fat and increasing lean body mass. An increase in lean body mass
      may reduce frailty and thus avoid functional impairment. Thus, providing GH to
      elderly CKD patients could potentially improve outcomes and quality of life by
      lowering the risk of frailty and associated functional impairment. There are few
      studies assessing the long-term effects of GH administration on symptoms of
      frailty in elderly patients with CKD. In this review we will try to shed some
      light on the trials assessing the administration of GH to elderly subjects and to
      patients with CKD and focus on the possible role GH administration may play to
      improve frailty and quality of life in those patients.

PMID- 19840348
TI  - Hospital care for children in developing countries: getting the evidence where it
      matters.

PMID- 19840349
TI  - EDCTP: a genuine north-south partnership.

PMID- 19840350
TI  - Intersectoral coordination, community empowerment and dengue prevention: six
      years of controlled interventions in Playa Municipality, Havana, Cuba.
AB  - OBJECTIVE: To document the process, outcome and effectiveness of a community
      based intervention for dengue control. METHODS: The primary intervention, focused
      on strengthening intersectoral coordination, was initiated by researchers in
      January 2000 in a pilot area in Playa municipality, Havana. In August 2002 health
      authorities extended the intervention to neighbouring areas, one of which was
      selected for evaluation. In August 2003 a complementary strategy, focused on
      community empowerment, was initiated in half of the pilot area. In our control
      area, routine dengue activities continued throughout the study period.
      Longitudinal process assessment was carried out using document analysis,
      interviews and group discussions. Random population surveys in 1999, 2002 and
      2005 assessed levels of participation and behavioural changes. Entomological
      surveillance data from 1999 to 2005 were used to determine effectiveness.
      RESULTS: Mean scores for participation in the pilot area were 1.6, 3.4 and 4.4 at
      baseline, and 2 years after initiating intersectoral coordination and
      intersectoral coordination plus community empowerment interventions,
      respectively. While in the control area little behavioural change was observed
      over time, changes were considerable in the pilot and extension areas, with 80%
      of households involved in the community empowerment intervention showed adequate
      behavioural patterns. The pilot and extension areas attained comparable
      entomological effectiveness with significantly lower Breteau indices (BIs) than
      the control area. The pilot (sub-) area with the community empowerment
      intervention reached BIs below 0.1 that continued to be significantly lower than
      the one in the control area until the end of the study. CONCLUSION: The study
      showed a trend in the levels and quality of participation, behavioural change and
      effectiveness of Aedes control from the routine activities only over an
      intervention with intersectoral coordination to one that combined intersectoral
      coordination and community empowerment approach.

PMID- 19840354
TI  - On the benefit of blood group molecular genotyping in cord blood banking.

PMID- 19840352
TI  - Irradiation of blood products for neonatal exchange transfusion.

PMID- 19840357
TI  - Oromandibular dystonia and hormonal factors: twelve years follow-up of a case
      report.
AB  - Oromandibular dystonia (OMD) is a focal neurological movement disorder
      characterized by involuntary sustained and often painful muscle contraction,
      usually producing repetitive movements or abnormal positions of the mouth, jaw
      and/or tongue. We report on a 30-year-old woman affected with OMD with a 12-year
      follow-up. Focal dystonia involved an involuntary activity of the lateral
      pterygoid muscles causing forceful jaw displacement in the maximal protrusive
      position. These episodes initially occurred during jaw function and increased up
      to an open-lock with bilateral pre-auricular pain. Dystonic spasms were absent
      during sleep and were reduced temporarily by sensory tricks. Treatment with
      botulinum toxin type A (BTX) was performed during three different sessions over a
      1-year period. Electromyographic-guided BTX injections into the lateral pterygoid
      muscles were given with cannula electrodes. Botox reduced the involuntary
      activity of the muscles. Recurrence and exacerbation of dystonic symptoms
      occurred during the two pregnancies and completely disappeared immediately after
      both deliveries with prolonged symptom-free periods. During the last 8 years, the
      patient had a slight relapse of symptoms during flu attacks, periods of stress
      and during menses. The temporal pattern of these symptoms indicates a possible
      relationship between OMD and hormonal factors.

PMID- 19840358
TI  - Dynamic viscoelastic properties of vinyl polysiloxane denture soft lining
      materials.
AB  - The aim of this study was to investigate the dynamic viscoelastic properties of
      seven commercially available vinyl polysiloxane denture soft lining materials.
      Five rectangular specimens (2 x 10 x 30 mm) were prepared from each material. The
      complex modulus E* (MPa) and loss tangent (tan delta) of each specimen were
      determined with a non-resonance forced vibration method using an automatic
      dynamic viscoelastometer at 1 Hz after 1 day of dry storage, and after 1, 30, 60,
      90 and 180 days of wet storage at 37 degrees C. All data were analysed using one
      way anova and Bonferroni/Dunn's test for multiple comparisons with a significance
      level of P < 0.01. All materials varied widely in terms of viscoelasticities and
      showed both an increase in E* and a decrease in tan delta at 1 Hz after the 1-day
      wet storage. After 60 days of wet storage, both E* and tan delta did not change
      significantly. The stiffer materials (>30% filler content) with high E* values
      (>2.00 MPa) showed elastic behaviour with tan delta values of around 0.03. The
      softer materials (6% filler content) with high tan delta values (initial value >
      0.10) showed viscous behaviour and were easily affected by water absorption after
      the 1-day wet storage. It can be concluded that for the proper selection of vinyl
      polysiloxane denture soft lining materials, it is very important to evaluate the
      viscoelastic properties after 60 days of wet storage.

PMID- 19840359
TI  - Decrease in stereognostic ability of the tongue with age.
AB  - Rehabilitation of eating and swallowing functions from the viewpoint of quality
      of life should attempt to restore not only the physical, but also sensory
      function. As the size and shape of the intra-oral bolus of food provides oral
      sensory information important for eating and swallowing, we investigated the
      stereognostic ability of the tongue in 269 young adults (mean age: 24.5 years)
      and 60 seniors (mean age: 80.5 years); all of whom had no eating or swallowing
      complaints. Assessment of the stereognostic ability involved identifying 20
      differently shaped test pieces placed in the oral cavity. The young adults
      identified a significantly higher number of differently shaped test pieces than
      the seniors (mean correct number of responses: 16.5 and 10.1 respectively; P <
      0.001). Gender and the presence of palatal covers did not have any significant
      effect on stereognostic ability. The test pieces were categorized into six groups
      based on the shape. When the young adults misidentified a piece, they often
      selected another piece within the same group, almost never selecting a piece from
      another group. The seniors, however, chose test pieces from different groups.
      Moreover, to determine whether stereognosis could be improved through training,
      we conducted training involving four senior subjects in their 80s, who correctly
      identified 10 or fewer pieces. After the training, the number of correct answers
      increased significantly (P < 0.05). These findings indicate that seniors show
      decreased stereognostic ability of the tongue compared with young adults and
      suggest the possibility of recovering the ability using our training method.

PMID- 19840360
TI  - Effect of denture base materials on mRNA expression of the adhesion-associated
      genes from the Streptococcus mutans biofilms.
AB  - Dental caries is one of the most important reasons for the failure of removable
      partial denture. The adhesion-associated genes of Streptococcus mutans, such as
      gtfBCD, ftf and gbpB, might play an important role in bacterial adhesion to
      denture base materials. Therefore, the aim of this study was to investigate the
      influence of denture base materials (heat-curing acrylic resins, cobalt-chromium
      alloy and ceramics served as control) on the formation of S. mutans biofilms and
      the mRNA expression of adhesion-associated genes. The viability of the bacteria
      in biofilms was determined by colony-forming units at 24 and 72 h, meanwhile one
      sample of each group was prepared for scanning electron microscope (SEM) at 24 h.
      A real-time reverse transcription polymerase chain-reaction was used to quantify
      the mRNA expression levels of gtfBCD, ftf and gbpB genes in the presence of
      various materials. The results revealed that acrylic resins had more S. mutans
      adhesion than Co-Cr alloy and ceramics in terms of the bacterial viability and
      SEM observation. The level of gtfBCD expression was the highest in ceramics group
      and the lowest in acrylic resins group in 24 h biofilms; however, acrylic resins
      had more gtfBC transcription significantly than other materials at 72 h (P <
      0.05). Ftf and gbpB were upregulated in 24 h biofilms on denture base materials
      compared with control (P < 0.05). These results suggested that the expression
      profiles of gtfBCD, ftf and gbpB were material-dependent and the physico-chemical
      properties of the materials might influence the transcription of these genes.
      Acrylic resins, which had the most bacterial adhesion, might affect biofilm
      formation via increased expression of ftf and gbpB at 24 h and gtfBC at 72 h.

PMID- 19840361
TI  - Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as
      measured by time in therapeutic range: a pilot study.
AB  - BACKGROUND: The efficacy and safety of vitamin K antagonists for the prevention
      of thromboembolism are dependent on the time for which the International
      Normalized Ratio (INR) is in the therapeutic range. The objective of our study
      was to determine the effect of introducing a simple two-step dosing algorithm, as
      compared with dosing by anticoagulation clinic staffs on the basis of their
      experience, on time in therapeutic range (TTR) of warfarin therapy. METHODS: We
      compared TTRs of all clinic patients before and after the introduction of a
      simple two-step dosing algorithm at a single anticoagulation clinic in Canada,
      between 1 August 2006 and 24 December 2008. TTR was calculated using the linear
      interpolation method of Rosendaal. RESULTS: We included 873 patients in the
      'before' phase and 1088 patients in the 'after' phase. Introduction of the dosing
      algorithm significantly increased TTR of patients with a therapeutic INR range of
      2-3 from 67.2% to 73.2% (P < 0.001), and that of patients with a therapeutic INR
      range of 2.5-3.5 from 49.8% to 63.8% (P < 0.001). CONCLUSIONS: The introduction
      of a simple two-step warfarin-dosing algorithm in place of dosing by experienced
      anticoagulation clinic staff significantly improved mean TTR for patients in a
      tertiary-care anticoagulation clinic. This inexpensive and widely applicable
      algorithm has the potential to improve warfarin control.

PMID- 19840362
TI  - Atomic force microscopy: a novel approach to the detection of nanosized blood
      microparticles.
AB  - BACKGROUND: Microparticles (MPs) are small vesicles released from cells of
      different origin, bearing surface antigens from parental cells. Elevated numbers
      of blood MPs have been reported in (cardio)vascular disorders and cancer. Most of
      these MPs are derived from platelets. OBJECTIVES: To investigate whether atomic
      force microscopy (AFM) can be used to detect platelet-derived MPs and to define
      their size distribution. METHODS: Blood MPs isolated from seven blood donors and
      three cancer patients were immobilized on a modified mica surface coated with an
      antibody against CD41 prior to AFM imaging. AFM was performed in liquid-tapping
      mode to detect CD41-positive MPs. In parallel, numbers of CD41-positive MPs were
      measured using flow cytometry. Mouse IgG1 isotype control was used as a negative
      control. RESULTS: AFM topography measurements of the number of CD41-positive MPs
      were reproducible (coefficient of variation=16%). Assuming a spherical shape of
      unbound MPs, the calculated diameter of CD41-positive MPs (dsph) ranged from 10
      to 475 nm (mean: 67.5+/-26.5 nm) and from 5 to 204 nm (mean: 51.4+/-14.9 nm) in
      blood donors and cancer patients, respectively. Numbers of CD41-positive MPs were
      1000-fold higher than those measured by flow cytometry (3-702x10(9) L(-1) plasma
      vs. 11-626x10(6) L(-1) plasma). After filtration of isolated MPs through a 0.22
      microm filter, CD41-positive MPs were still detectable in the filtrate by AFM
      (mean dsph: 37.2+/-11.6 nm), but not by flow cytometry. CONCLUSIONS: AFM provides
      a novel method for the sensitive detection of defined subsets of MPs in the
      nanosize range, far below the lower limit of what can be measured by conventional
      flow cytometry.

PMID- 19840363
TI  - The glycoprotein Ibalpha-von Willebrand factor interaction induces platelet
      apoptosis.
AB  - BACKGROUND: The interaction of glycoprotein (GP) Ibalpha with von Willebrand
      factor (VWF) initiates platelet adhesion, and simultaneously triggers
      intracellular signaling cascades leading to platelet aggregation and thrombus
      formation. Some of the signaling events are similar to those occurring during
      apoptosis, however, it is still unclear whether platelet apoptosis is induced by
      the GPIbalpha-VWF interaction. OBJECTIVES: To investigate whether the GPIbalpha
      VWF interaction induces platelet apoptosis and the role of 14-3-3zeta in
      apoptotic signaling. METHODS: Apoptotic events were assessed in platelets or
      Chinese hamster ovary (CHO) cells expressing wild-type (1b9) or mutant GPIb-IX
      interacting with VWF by flow cytometry or western blotting. RESULTS: Ristocetin
      induced GPIbalpha-VWF interaction elicited apoptotic events in platelets,
      including phosphatidylserine exposure, elevations of Bax and Bak, gelsolin
      cleavage, and depolarization of mitochondrial inner transmembrane potential.
      Apoptotic events were also elicited in platelets exposed to pathologic shear
      stresses in the presence of VWF; however, the shear-induced apoptosis was
      eliminated by the anti-GPIbalpha antibody AK2. Furthermore, apoptotic events
      occurred in 1b9 cells stimulated with VWF and ristocetin, but were significantly
      diminished in two CHO cell lines expressing mutant GPIb-IX with GPIbalpha
      truncated at residue 551 or a serine-to-alanine mutation at the 14-3-3zeta
      binding site in GPIbalpha. CONCLUSIONS: This study demonstrates that the
      GPIbalpha-VWF interaction induces apoptotic events in platelets, and that the
      association of 14-3-3zeta with the cytoplasmic domain of GPIbalpha is essential
      for apoptotic signaling. This finding may suggest a novel mechanism for platelet
      clearance or some thrombocytopenic diseases.

PMID- 19840364
TI  - Successful antiviral therapy determines a significant decrease in squamous cell
      carcinoma antigen-associated (SCCA) variants' serum levels in anti-HCV positive
      cirrhotic patients.
AB  - Aberrant squamous cell carcinoma antigen (SCCA) expression is an early event in
      hepatocarcinogenesis, and increasing serum levels of SCCA variants IgM immune
      complexes (SCCA-IgM IC) have been found in cirrhotic patients developing
      hepatocellular carcinoma (HCC). We longitudinally evaluated a cohort of cirrhotic
      patients with hepatitis C virus infection (HCV) who underwent pegylated
      interferon (PEG-IFN) and ribavirin treatment. SCCA-IgM IC levels were assessed in
      the sera of 33 cirrhotic patients with HCV (21 males, median age 57 years)
      before, at the end and at 6-month and 1-year follow-up after treatment with PEG
      IFN and ribavirin. SCCA-IgM IC serum levels (arbitrary units/mL, AU/mL) were
      evaluated according to treatment outcome: sustained virological response (SVR) vs
      nonresponse (NR). Overall, 15 patients obtained a SVR to antiviral therapy (45%).
      There was no significant difference in baseline SCCA-IgM IC serum levels between
      SVR and NR patients. When compared to baseline (451.2 AU/mL), SVR patients showed
      a significant decrease in median SCCA-IgM IC serum levels at the end of treatment
      (186.8 AU/mL, P = 0.013) and at both 6-month (96.8 AU/mL, P < 0.001) and 1-year
      follow-up (52.4 AU/mL, P < 0.001), while no significant modification was observed
      in NR patients. In patients with HCV-related liver cirrhosis, successful
      antiviral therapy is associated with a dramatic and significant decrease in SCCA
      IC serum levels. Because of the pathophysiological correlation between SCCA and
      liver carcinogenesis, it is hypothesized that in patients with liver cirrhosis,
      SVR may be accompanied by a decreased proliferative stimulation.

PMID- 19840365
TI  - The prevalence of hepatitis C virus (HCV) infection in HIV-positive individuals
      in the UK - trends in HCV testing and the impact of HCV on HIV treatment
      outcomes.
AB  - We examined the prevalence of hepatitis C virus (HCV) infection among HIV
      positive individuals in the UK, trends in HCV testing and the impact of HCV on
      HIV treatment outcomes. Trends over time in HCV prevalence were calculated using
      each patient's most recent HCV status at the end of each calendar year. Logistic
      regression was used to identify factors associated with having a HCV antibody
      test, and Cox regression was used to determine whether HCV status was associated
      with the time to experiencing an immunological response to highly active
      antiretroviral treatment (HAART), time to virological response and viral rebound.
      Of the 31,765 HIV-positive individuals seen for care between January 1996 and
      September 2007, 20,365 (64.1%) individuals were tested for HCV, and 1807 (8.9%)
      had detectable HCV antibody. The proportion of patients in follow-up ever tested
      for HCV increased over time, from 782/8505 (9.2%) in 1996 to 14,280/17,872
      (79.9%) in 2007. Nine thousand six hundred and sixty-nine individuals started
      HAART for the first time in or after January 2000, of whom, 396 (4.1%) were HCV
      positive. Presence of HCV infection did not affect initial virological response,
      virological rebound or immunological response. The cumulative prevalence of HCV
      in the UK CHIC Study is 8.9%. Despite UK guidelines, over 20% of HIV-positive
      individuals have not had their HCV status determined by 2007. HCV infection had
      no impact on HIV virological outcomes or immunological response to HIV treatment.
      The long-term impact on morbidity and mortality remain to be determined.

PMID- 19840366
TI  - Splenectomy and antiviral treatment for thrombocytopenic patients with chronic
      hepatitis C virus infection.
AB  - Thrombocytopenic patients with chronic hepatitis C virus (HCV) infection are poor
      candidates for antiviral treatment with interferon (IFN), but no standard
      treatment for thrombocytopenia has yet been established. We evaluated the safety
      of splenectomy and its efficacy for the initiation and continuation of antiviral
      therapy. From March 2003 to April 2006, 10 patients (mean age 62.5 years) with
      HCV-related cirrhosis, low platelet count (<==106 000/mm(3)) and splenomegaly
      (spleen size >==10 cm) underwent splenectomy. Platelet counts significantly
      increased at 4-8 weeks after splenectomy [pre: 64 200 +/- 6900/mm(3)vs post 209
      000 +/- 40 600/mm(3) (P = 0.004)]. No severe operative complications were
      observed. All patients subsequently received antiviral therapy. Of the eight
      patients who were infected with HCV genotype 1 and had a high viral load (>==100
      KIU/mL), four received combination therapy with pegylated IFNalpha-2b plus
      ribavirin, and the other four received standard IFNalpha-2b plus ribavirin. One
      patient infected with HCV genotype 2 and another with HCV genotype 1 and a low
      viral load (<100 KIU/mL) were treated with pegylated IFNalpha-2a. Six patients
      achieved sustained virologic response (SVR). Among four patients who failed to
      achieve SVR, one was given retreatment with pegylated IFN plus ribavirin, and the
      other three received low-dose long-term IFN therapy. Although this study was
      small, the treatment results were similar to those for patients without
      thrombocytopenia and suggested that splenectomy would not reduce the antiviral
      efficacy of IFNalpha-based treatment.

PMID- 19840367
TI  - Visfatin serum levels in chronic hepatitis C patients.
AB  - Visfatin is a new adipokine involved in several processes. The data concerning
      visfatin in chronic hepatitis C (CHC) is small. To assess visfatin serum
      concentration and to study its association with biochemical and morphological
      features in CHC. Seventy nonobese patients with CHC (Group 1) confirmed by the
      presence of serum hepatitis C virus (HCV)-RNA and 20 healthy volunteers (Group
      2), similar in age and BMI with normal fasting glucose and lipid profile were
      included. Visfatin was significantly increased in Group 1 compared with Group 2
      (55.6 +/- 23.1 vs 23.7 +/- 3.8 ng/mL; P < 0.001). Visfatin was negatively
      associated with necro-inflammatory activity grade (r = -0.36; P = 0.007). The
      lowest levels were found in patients with the most advanced inflammation: grades
      3-4 - 46.8 +/- 17.1, grade 2 - 52.6 +/- 18.4 and grade 1 - 75.2 +/- 27.6 ng/mL; P
      = 0.017. A significant difference was also shown comparing patients with minimal
      inflammatory activity to the rest of the cohort (P = 0.009). Visfatin receiver
      operating characteristic curve analysis for different necro-inflammatory activity
      - grade 1 vs grades 3-4 with area under the curve 0.81 indicated a good
      discriminant power for differentiation of moderate/severe inflammation, with the
      cut-off set at 57.6 ng/mL (sensitivity 75%, specificity 90%, positive predictive
      value 0.90, negative predictive value 0.75). Serum visfatin concentration
      increases significantly in CHC patients. These findings suggest that visfatin is
      important in the pathogenesis of the inflammatory process in CHC. Visfatin may
      play a dual role as a pro-inflammatory or/and protective factor. The measurement
      of visfatin serum concentration may serve as an additional tool in distinguishing
      more advanced grades of the necro-inflammatory activity.

PMID- 19840368
TI  - Patient delay in cancer studies: a discussion of methods and measures.
AB  - BACKGROUND: There is no validated way of measuring the prevalence and duration of
      patient delay, and we do not know how people perceive and define the time
      intervals they are asked to report in patient delay studies. This lack of a
      validated measure hampers research in patient delay and is counterproductive to
      efforts directed at securing early diagnosis of cancer. DISCUSSION: The main
      argument of the present paper is that current studies on patient delay do not
      sufficiently consider existing theories on symptom interpretation. It is
      illustrated that the interpretation of bodily sensations as symptoms related to a
      specific cancer diagnosis is embedded within a social and cultural context. We
      therefore cannot assume that respondents define delay periods in identical ways.
      SUMMARY: In order to improve the validity of patient delay studies, it is
      suggested that research be strengthened on three counts: More research should be
      devoted to symptom interpretation processes, more research should seek to
      operationalise patient delay, and, importantly, more research is needed to
      develop valid instruments for measuring patient delay.

PMID- 19840369
TI  - Overview of the Alberta Kidney Disease Network.
AB  - BACKGROUND: The Alberta Kidney Disease Network is a collaborative nephrology
      research organization based on a central repository of laboratory and
      administrative data from the Canadian province of Alberta. DESCRIPTION: The
      laboratory data within the Alberta Kidney Disease Network can be used to define
      patient populations, such as individuals with chronic kidney disease (using serum
      creatinine measurements to estimate kidney function) or anemia (using hemoglobin
      measurements). The administrative data within the Alberta Kidney Disease Network
      can also be used to define cohorts with common medical conditions such as
      hypertension and diabetes. Linkage of data sources permits assessment of socio
      demographic information, clinical variables including comorbidity, as well as
      ascertainment of relevant outcomes such as health service encounters and events,
      the occurrence of new specified clinical outcomes and mortality. CONCLUSION: The
      unique ability to combine laboratory and administrative data for a large
      geographically defined population provides a rich data source not only for
      research purposes but for policy development and to guide the delivery of health
      care. This research model based on computerized laboratory data could serve as a
      prototype for the study of other chronic conditions.

PMID- 19840370
TI  - Bayesian inference of biochemical kinetic parameters using the linear noise
      approximation.
AB  - BACKGROUND: Fluorescent and luminescent gene reporters allow us to dynamically
      quantify changes in molecular species concentration over time on the single cell
      level. The mathematical modeling of their interaction through multivariate
      dynamical models requires the development of effective statistical methods to
      calibrate such models against available data. Given the prevalence of
      stochasticity and noise in biochemical systems inference for stochastic models is
      of special interest. In this paper we present a simple and computationally
      efficient algorithm for the estimation of biochemical kinetic parameters from
      gene reporter data. RESULTS: We use the linear noise approximation to model
      biochemical reactions through a stochastic dynamic model which essentially
      approximates a diffusion model by an ordinary differential equation model with an
      appropriately defined noise process. An explicit formula for the likelihood
      function can be derived allowing for computationally efficient parameter
      estimation. The proposed algorithm is embedded in a Bayesian framework and
      inference is performed using Markov chain Monte Carlo. CONCLUSION: The major
      advantage of the method is that in contrast to the more established diffusion
      approximation based methods the computationally costly methods of data
      augmentation are not necessary. Our approach also allows for unobserved variables
      and measurement error. The application of the method to both simulated and
      experimental data shows that the proposed methodology provides a useful
      alternative to diffusion approximation based methods.

PMID- 19840371
TI  - Review of epidemiologic data on the debate over smokeless tobacco's role in harm
      reduction.
AB  - Some tobacco researchers have argued that the European Union should remove its
      ban on a form of low-nitrosamine smokeless tobacco referred to as Swedish 'snus'.
      This argument has developed in to an international debate over the use of
      smokeless tobacco as a measure of harm reduction for smokers. Leading authorities
      in the USA have firmly stated that there is no safe tobacco - a message which
      does not allow for any discussion of comparative tobacco risks. This commentary
      is intended to review the origin of the controversy over Swedish 'snus', to
      examine briefly the meta-analysis on cancer risks by Peter Lee and Jan Hamling
      (published in July in BMC Medicine) and to discuss the anticipated direction of
      the debate on tobacco-harm reduction in the USA. We anticipate that much of the
      debate will shift from the discussion of epidemiologic data to the discussion of
      the marketing, health communication and economics of smokeless tobacco. While the
      Food and Drug Administration's newly approved authority over tobacco will
      undoubtedly affect the smokeless products, it may not be the sole determinant of
      harm reduction's fate in the USA. See associated research article by Lee and
      Hamling: http://www.biomedcentral.com/1741-7015/7/36.

PMID- 19840372
TI  - The use of schools for malaria surveillance and programme evaluation in Africa.
AB  - Effective malaria control requires information on both the geographical
      distribution of malaria risk and the effectiveness of malaria interventions. The
      current standard for estimating malaria infection and impact indicators are
      household cluster surveys, but their complexity and expense preclude frequent and
      decentralized monitoring. This paper reviews the historical experience and
      current rationale for the use of schools and school children as a complementary,
      inexpensive framework for planning, monitoring and evaluating malaria control in
      Africa. Consideration is given to (i) the selection of schools; (ii) diagnosis of
      infection in schools; (iii) the representativeness of schools as a proxy of the
      communities they serve; and (iv) the increasing need to evaluate interventions
      delivered through schools. Finally, areas requiring further investigation are
      highlighted.

PMID- 19840373
TI  - Expanded progenitor populations, vitreo-retinal abnormalities, and Muller glial
      reactivity in the zebrafish leprechaun/patched2 retina.
AB  - BACKGROUND: The roles of the Hedgehog (Hh) pathway in controlling vertebrate
      retinal development have been studied extensively; however, species- and context
      dependent findings have provided differing conclusions. Hh signaling has been
      shown to control both population size and cell cycle kinetics of proliferating
      retinal progenitors, and to modulate differentiation within the retina by
      regulating the timing of cell cycle exit. While cell cycle exit has in turn been
      shown to control cell fate decisions within the retina, a direct role for the Hh
      pathway in retinal cell fate decisions has yet to be established in vivo.
      RESULTS: To gain further insight into Hh pathway function in the retina, we have
      analyzed retinal development in leprechaun/patched2 mutant zebrafish. While
      lep/ptc2 mutants possessed more cells in their retinas, all cell types, except
      for Muller glia, were present at identical ratios as those observed in wild-type
      siblings. lep/ptc2 mutants possessed a localized upregulation of GFAP, a marker
      for 'reactive' glia, as well as morphological abnormalities at the vitreo-retinal
      interface, where Muller glial endfeet terminate. In addition, analysis of the
      over-proliferation phenotype at the ciliary marginal zone (CMZ) revealed that the
      number of proliferating progenitors, but not the rate of proliferation, was
      increased in lep/ptc2 mutants. CONCLUSION: Our results indicate that Patched2
      dependent Hh signaling does not likely play an integral role in neuronal cell
      fate decisions in the zebrafish retina. ptc2 deficiency in zebrafish results in
      defects at the vitreo-retinal interface and Muller glial reactivity. These
      phenotypes are similar to the ocular abnormalities observed in human patients
      suffering from Basal Cell Naevus Syndrome (BCNS), a disorder that has been linked
      to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2), and
      point to the utility of the lep/ptc2 mutant line as a model for the study of BCNS
      related ocular pathologies. Our findings regarding CMZ progenitor proliferation
      suggest that, in the zebrafish retina, Hh pathway activity may not affect cell
      cycle kinetics; rather, it likely regulates the size of the retinal progenitor
      pool in the CMZ.

PMID- 19840374
TI  - TIde: a software for the systematic scanning of drug targets in kinetic network
      models.
AB  - BACKGROUND: During the stages of the development of a potent drug candidate
      compounds can fail for several reasons. One of them, the efficacy of a candidate,
      can be estimated in silico if an appropriate ordinary differential equation model
      of the affected pathway is available. With such a model at hand it is also
      possible to detect reactions having a large effect on a certain variable such as
      a substance concentration. RESULTS: We show an algorithm that systematically
      tests the influence of activators and inhibitors of different type and strength
      acting at different positions in the network. The effect on a quantity to be
      selected (e.g. a steady state flux or concentration) is calculated. Moreover,
      combinations of two inhibitors or one inhibitor and one activator targeting
      different network positions are analysed. Furthermore, we present TIde (Target
      Identification), an open source, platform independent tool to investigate
      ordinary differential equation models in the common systems biology markup
      language format. It automatically assigns the respectively altered kinetics to
      the inhibited or activated reactions, performs the necessary calculations, and
      provides a graphical output of the analysis results. For illustration, TIde is
      used to detect optimal inhibitor positions in simple branched networks, a
      signalling pathway, and a well studied model of glycolysis in Trypanosoma brucei.
      CONCLUSION: Using TIde, we show in the branched models under which conditions
      inhibitions in a certain pathway can affect a molecule concentrations in a
      different. In the signalling pathway we illuminate which inhibitions have an
      effect on the signalling characteristics of the last active kinase. Finally, we
      compare our set of best targets in the glycolysis model with a similar analysis
      showing the applicability of our tool.

PMID- 19840375
TI  - Prevalence of dementia and major dementia subtypes in Spanish populations: a
      reanalysis of dementia prevalence surveys, 1990-2008.
AB  - BACKGROUND: This study describes the prevalence of dementia and major dementia
      subtypes in Spanish elderly. METHODS: We identified screening surveys, both
      published and unpublished, in Spanish populations, which fulfilled specific
      quality criteria and targeted prevalence of dementia in populations aged 70 years
      and above. Surveys covering 13 geographically different populations were selected
      (prevalence period: 1990-2008). Authors of original surveys provided
      methodological details of their studies through a systematic questionnaire and
      also raw age-specific data. Prevalence data were compared using direct adjustment
      and logistic regression. RESULTS: The reanalyzed study population (aged 70 year
      and above) was composed of Central and North-Eastern Spanish sub-populations
      obtained from 9 surveys and totaled 12,232 persons and 1,194 cases of dementia
      (707 of Alzheimer's disease, 238 of vascular dementia). Results showed high
      variation in age- and sex-specific prevalence across studies. The reanalyzed
      prevalence of dementia was significantly higher in women; increased with age,
      particularly for Alzheimer's disease; and displayed a significant geographical
      variation among men. Prevalence was lowest in surveys reporting participation
      below 85%, studies referred to urban-mixed populations and populations diagnosed
      by psychiatrists. CONCLUSION: Prevalence of dementia and Alzheimer's disease in
      Central and North-Eastern Spain is higher in females, increases with age, and
      displays considerable geographic variation that may be method-related. People
      suffering from dementia and Alzheimer's disease in Spain may approach 600,000 and
      400,000 respectively. However, existing studies may not be completely appropriate
      to infer prevalence of dementia and its subtypes in Spain until surveys in
      Southern Spain are conducted.

PMID- 19840376
TI  - CHD5 is down-regulated through promoter hypermethylation in gastric cancer.
AB  - BACKGROUND: Nonhistone chromosomal proteins in concert with histones play
      important roles in the replication and repair of DNA and in the regulation of
      gene expression. The deregulation of these proteins can contribute to the
      development of a variety of diseases such as cancer. As a nonhistone chromosomal
      protein, chromodomain helicase DNA binding protein 5 (CHD5) has recently been
      identified as the product of a novel tumor suppressor gene (TSG), promoting the
      transcription of p19ink4a and p16arf. The inactivation of CHD5 was achieved
      partly through genetic deletion since it is located in 1p36, a region frequently
      deleted in human tumors. In this study, we aim to study the involvement of CHD5
      in gastric cancer, the second most common cancer worldwide. METHODS: CHD5
      expression in a panel of gastric cancer cells were determined by quantitative RT
      PCR. The methylation of CHD5 was evaluated by methylation specific PCR and
      bisulfite genome sequencing. The effect of CHD5 on growth of gastric cancer cells
      was tested by colony formation assay. RESULTS: CHD5 expression was down-regulated
      in all of gastric cancer cell lines used (100%, 7/7) and significantly restored
      after pharmacological demethylation. Methylation of CHD5 promoter was detected in
      all of seven gastric cancer cell lines and in the majority of primary gastric
      carcinoma tissues examined (73%, 11/15). Finally, ectopic expression of CHD5 in
      gastric cancer cells led to a significant growth inhibition. CONCLUSION: CHD5 was
      a TSG epigenetically down-regulated in gastric cancer.

PMID- 19840377
TI  - Machine learning integration for predicting the effect of single amino acid
      substitutions on protein stability.
AB  - BACKGROUND: Computational prediction of protein stability change due to single
      site amino acid substitutions is of interest in protein design and analysis. We
      consider the following four ways to improve the performance of the currently
      available predictors: (1) We include additional sequence- and structure-based
      features, namely, the amino acid substitution likelihoods, the equilibrium
      fluctuations of the alpha- and beta-carbon atoms, and the packing density. (2) By
      implementing different machine learning integration approaches, we combine
      information from different features or representations. (3) We compare
      classification vs. regression methods to predict the sign vs. the output of
      stability change. (4) We allow a reject option for doubtful cases where the risk
      of misclassification is high. RESULTS: We investigate three different approaches:
      early, intermediate and late integration, which respectively combine features,
      kernels over feature subsets, and decisions. We perform simulations on two data
      sets: (1) S1615 is used in previous studies, (2) S2783 is the updated version (as
      of July 2, 2009) extracted also from ProTherm. For S1615 data set, our highest
      accuracy using both sequence and structure information is 0.842 on cross
      validation and 0.904 on testing using early integration. Newly added features,
      namely, local compositional packing and the mobility extent of the mutated
      residues, improve accuracy significantly with intermediate integration. For S2783
      data set, we also train regression methods to estimate not only the sign but also
      the amount of stability change and apply risk-based classification to reject when
      the learner has low confidence and the loss of misclassification is high. The
      highest accuracy is 0.835 on cross-validation and 0.832 on testing using only
      sequence information. The percentage of false positives can be decreased to less
      than 0.005 by rejecting 10 per cent using late integration. CONCLUSION: We find
      that in both early and late integration, combining inputs or decisions is useful
      in increasing accuracy. Intermediate integration allows assessing the
      contributions of individual features by looking at the assigned weights. Overall
      accuracy of regression is not better than that of classification but it has less
      false positives, especially when combined with the reject option. The server for
      stability prediction for three integration approaches and the data sets are
      available at http://www.prc.boun.edu.tr/appserv/prc/mlsta.

PMID- 19840378
TI  - Gastroesophageal reflux in mechanically ventilated pediatric patients and its
      relation to ventilator-associated pneumonia.
AB  - INTRODUCTION: The objective was to determine the frequency of gastroesophageal
      reflux (GER) in mechanically ventilated pediatric patients and its role as a risk
      factor for ventilator-associated pneumonia (VAP), which may be enhanced among
      those patients. METHODS: The study is a prospective cohort study of mechanically
      ventilated pediatric patients in the pediatric intensive care unit (PICU) of Ain
      Shams University Children's Hospital. It was conducted in 24 mechanically
      ventilated patients (16 of them developed VAP and 8 did not, with mean age of
      16.6 +/- 20.5 and 18.6 +/- 22.4 months respectively). Esophageal 24-hour pH-metry
      beside clinical and laboratory evaluation of their underlying problem and
      severity of their condition were carried out. RESULTS: All VAP patients had GER
      (50% alkaline reflux, 12.5% acidic reflux and 37.5% combined reflux) compared to
      75% of non-VAP ones (100% alkaline reflux). The mean total reflux time was
      significantly longer among VAP (50 minutes) versus non-VAP (3 minutes) patients.
      There was significant increase in acidic reflux parameters among non-survivors
      versus survivors (P < 0.001). For VAP mortality, total acidic reflux at a cut-off
      value of 28.6 minutes is found to be a mortality predictor with a sensitivity of
      100% and a specificity of 100%. CONCLUSIONS: GER is a constant incident in
      mechanically ventilated pediatric patients, with alkaline reflux being more
      common than acidic reflux. Both acidic and alkaline refluxes were found to be
      associated with the development of VAP and total reflux time was found to be a
      reliable predictor of VAP. Moreover, acidic reflux was found to be more related
      to mortality than alkaline reflux.

PMID- 19840379
TI  - Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of
      sulfasalazine for the treatment of progressing malignant gliomas in adults.
AB  - BACKGROUND: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport
      inhibitor, has demonstrated a strong antitumoral potential in preclinical models
      of malignant gliomas. As it presents an excellent safety profile, we initiated a
      phase 1/2 clinical study of this anti-inflammatory drug for the treatment of
      recurrent WHO grade 3 and 4 astrocytic gliomas in adults. METHODS: 10 patients
      with advanced recurrent anaplastic astrocytoma (n = 2) or glioblastoma (n = 8)
      aged 32-62 years were recruited prior to the planned interim analysis of the
      study. Subjects were randomly assigned to daily doses of 1.5, 3, 4.5, or 6 grams
      of oral sulfasalazine, and treated until clinical or radiological evidence of
      disease progression or the development of serious or unbearable side effects.
      Primary endpoints were the evaluation of toxicities according to the CTCAE v.3.0,
      and the observation of radiological tumor responses based on MacDonald criteria.
      RESULTS: No clinical response was observed. One tumor remained stable for 2
      months with sulfasalazine treatment, at the lowest daily dose of the drug. The
      median progression-free survival was 32 days. Side effects were common, as all
      patients developed grade 1-3 adverse events (mean: 7.2/patient), four patients
      developed grade 4 toxicity. Two patients died while on treatment or shortly after
      its discontinuation. CONCLUSION: Although the proper influence of sulfasalazine
      treatment on patient outcome was difficult to ascertain in these debilitated
      patients with a large tumor burden (median KPS = 50), ISRCTN45828668 was
      terminated after its interim analysis. This study urges to exert cautiousness in
      future trials of Sulfasalazine for the treatment of malignant gliomas. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN45828668.

PMID- 19840380
TI  - Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1
      integrase.
AB  - BACKGROUND: The 18 residue tail abutting the SH3 fold that comprises the heart of
      the C-terminal domain is the only part of HIV-1 integrase yet to be visualized by
      structural biology. To ascertain the role of the tail region in integrase
      function and HIV-1 replication, a set of deletion mutants that successively
      lacked three amino acids was constructed and analyzed in a variety of biochemical
      and virus infection assays. HIV-1/2 chimers, which harbored the analogous 23-mer
      HIV-2 tail in place of the HIV-1 sequence, were also studied. Because integrase
      mutations can affect steps in the replication cycle other than integration,
      defective mutant viruses were tested for integrase protein content and reverse
      transcription in addition to integration. The F185K core domain mutation, which
      increases integrase protein solubility, was furthermore analyzed in a subset of
      mutants. RESULTS: Purified proteins were assessed for in vitro levels of 3'
      processing and DNA strand transfer activities whereas HIV-1 infectivity was
      measured using luciferase reporter viruses. Deletions lacking up to 9 amino acids
      (1-285, 1-282, and 1-279) displayed near wild-type activities in vitro and during
      infection. Further deletion yielded two viruses, HIV-1(1-276) and HIV-1(1-273),
      that displayed approximately two and 5-fold infectivity defects, respectively,
      due to reduced integrase function. Deletion mutant HIV-1(1-270) and the HIV-1/2
      chimera were non-infectious and displayed approximately 3 to 4-fold reverse
      transcription in addition to severe integration defects. Removal of four
      additional residues, which encompassed the C-terminal beta strand of the SH3
      fold, further compromised integrase incorporation into virions and reverse
      transcription. CONCLUSION: HIV-1(1-270), HIV-1(1-266), and the HIV-1/2 chimera
      were typed as class II mutant viruses due to their pleiotropic replication
      defects. We speculate that residues 271-273 might play a role in mediating the
      known integrase-reverse transcriptase interaction, as their removal unveiled a
      reverse transcription defect. The F185K mutation reduced the in vitro activities
      of 1-279 and 1-276 integrases by about 25%. Mutant proteins 1-279/F185K and 1
      276/F185K are therefore highlighted as potential structural biology candidates,
      whereas further deleted tail variants (1-273/F185K or 1-270/F185K) are less
      desirable due to marginal or undetectable levels of integrase function.

PMID- 19840381
TI  - A theory of organizational readiness for change.
AB  - BACKGROUND: Change management experts have emphasized the importance of
      establishing organizational readiness for change and recommended various
      strategies for creating it. Although the advice seems reasonable, the scientific
      basis for it is limited. Unlike individual readiness for change, organizational
      readiness for change has not been subject to extensive theoretical development or
      empirical study. In this article, I conceptually define organizational readiness
      for change and develop a theory of its determinants and outcomes. I focus on the
      organizational level of analysis because many promising approaches to improving
      healthcare delivery entail collective behavior change in the form of systems
      redesign--that is, multiple, simultaneous changes in staffing, work flow,
      decision making, communication, and reward systems. DISCUSSION: Organizational
      readiness for change is a multi-level, multi-faceted construct. As an
      organization-level construct, readiness for change refers to organizational
      members' shared resolve to implement a change (change commitment) and shared
      belief in their collective capability to do so (change efficacy). Organizational
      readiness for change varies as a function of how much organizational members
      value the change and how favorably they appraise three key determinants of
      implementation capability: task demands, resource availability, and situational
      factors. When organizational readiness for change is high, organizational members
      are more likely to initiate change, exert greater effort, exhibit greater
      persistence, and display more cooperative behavior. The result is more effective
      implementation. SUMMARY: The theory described in this article treats
      organizational readiness as a shared psychological state in which organizational
      members feel committed to implementing an organizational change and confident in
      their collective abilities to do so. This way of thinking about organizational
      readiness is best suited for examining organizational changes where collective
      behavior change is necessary in order to effectively implement the change and, in
      some instances, for the change to produce anticipated benefits. Testing the
      theory would require further measurement development and careful sampling
      decisions. The theory offers a means of reconciling the structural and
      psychological views of organizational readiness found in the literature. Further,
      the theory suggests the possibility that the strategies that change management
      experts recommend are equifinal. That is, there is no 'one best way' to increase
      organizational readiness for change.

PMID- 19840383
TI  - Bourgeois queens and high stakes games in the ant Aphaenogaster senilis.
AB  - BACKGROUND: Many animals face some form of conflict over reproductive
      opportunities. Queen selection in social insect colonies represents a high-stakes
      conflict where competition occurs among multiple queens for a few or a single
      reproductive role(s). The outcome of the contest is critical to the fitness of
      all colony individuals as most are sterile, and thus represents a conflict at
      multiple levels. Aphaenogaster senilis is a monogynous, monandrous, fission
      performing ant, in which queen selection occurs during colony fission and when
      replacement queens are produced to overcome orphaning. First-born queens are
      usually behaviourally dominant over subsequent queens, and eventually inherit the
      colony. We investigated the importance of physical dominance in queen selection
      in orphaned groups by manipulating the fighting ability of first-born queens via
      mandibular ablation. RESULTS: First emerged queens were heavier than second
      emerged queens, performed almost all aggression, were behaviourally dominant 92%
      of the time, and prevailed in 76% of groups after co-existing for 16 days on
      average. Mandibular ablation had no effect on queen behaviour or contest outcome.
      CONCLUSION: Aggression is probably ritualised and contests are decided by workers
      based on relative queen fertility. First-born queens thus have an inherent
      advantage over second-born queens as they have more time to develop ovaries.
      Subordinates never retaliated against aggression from dominants and this lack of
      retaliation can be interpreted as a form of bourgeois strategy as dominants were
      almost always first-born. However, the lack of alternative reproductive options
      makes not-fighting effectively a form of suicide. High relatedness between full
      sister queens means that subordinates may be better off sacrificing themselves
      than risking injury to both queens by fighting.

PMID- 19840382
TI  - Widespread variation in transcript abundance within and across developmental
      stages of Trypanosoma brucei.
AB  - BACKGROUND: Trypanosoma brucei, the causative agent of African sleeping sickness,
      undergoes a complex developmental cycle that takes place in mammalian and insect
      hosts and is accompanied by changes in metabolism and cellular morphology. While
      differences in mRNA expression have been described for many genes, genome-wide
      expression analyses have been largely lacking. Trypanosomatids represent a unique
      case in eukaryotes in that they transcribe protein-coding genes as large
      polycistronic units, and rarely regulate gene expression at the level of
      transcription initiation. RESULTS: Here we present a comprehensive analysis of
      mRNA expression in several stages of parasite development. Utilizing microarrays
      that have multiple copies of multiple probes for each gene, we were able to
      demonstrate with a high degree of statistical confidence that approximately one
      fourth of genes show differences in mRNA expression levels in the stages
      examined. These include complex patterns of gene expression within gene families,
      including the large family of variant surface glycoproteins (VSGs) and their
      relatives, where we have identified a number of constitutively expressed family
      members. Furthermore, we were able to assess the relative abundance of all
      transcripts in each stage, identifying the genes that are either weakly or highly
      expressed. Very few genes show no evidence of expression. CONCLUSION: Despite the
      lack of gene regulation at the level of transcription initiation, our results
      reveal extensive regulation of mRNA abundance associated with different life
      cycle and growth stages. In addition, analysis of variant surface glycoprotein
      gene expression reveals a more complex picture than previously thought. These
      data provide a valuable resource to the community of researchers studying this
      lethal agent.

PMID- 19840384
TI  - Pathway for inpatients with depressive episode in Flemish psychiatric hospitals:
      a qualitative study.
AB  - BACKGROUND: Within the context of a biopsychosocial model of the treatment of
      depressive episodes, a multidisciplinary approach is needed. Clinical pathways
      have been developed and implemented in hospitals to support multidisciplinary
      teamwork. The aim of this study is to explore current practice for the treatment
      of depressive episodes in Flemish psychiatric hospitals. Current practice in
      different hospitals is studied to get an idea of the similarities (outlined as a
      pathway) and the differences in the treatment of depressive episodes. METHODS: A
      convenience sample of 11 Flemish psychiatric hospitals participated in this
      qualitative study. Semi-structured interviews were conducted with different types
      of health care professionals (n = 43). The websites of the hospitals were
      searched for information on their approach to treating depressive episodes.
      RESULTS: A flow chart was made including the identified stages of the pathway:
      pre-admission, admission (observation and treatment), discharge and follow-up
      care. The characteristics of each stage are described. Although the stages are
      identified in all hospitals, differences between hospitals on various levels of
      the pathway exist. Hospitals emphasized the individual approach of each patient.
      The results point to a biopsychosocial approach to treating depressive episodes.
      CONCLUSION: This study outlined current practice as a pathway for Flemish
      inpatients with depressive episodes. Within the context of surveillance of
      quality and quantity of care, this study may encourage hospitals to consider
      developing clinical pathways.

PMID- 19840386
TI  - Metabolic syndrome in children and adolescents - criteria for diagnosis.
AB  - In recent years, there has been a greater concern about the presence of obesity
      and metabolic syndrome in children and adolescents. However, there is no
      consensus regarding the diagnosis of metabolic syndrome in children and
      adolescents. It is evident that each component of the syndrome must be identified
      as early as possible in order to prevent definitive lesions. The question is how
      to do this and which cut-offs must be adopted for this diagnosis. For a matter of
      convenience, the definition chosen as the most appropriate is the one proposed by
      the IDF, with cut-offs fixed for pressure, lipids and glycemia, and abdominal
      circumference points assessed by percentile. Although on the one hand this
      definition could fail to include some children in the diagnosis of Metabolic
      Syndrome, on the other hand, it would be of easier acceptance as it does not use
      multiple tables to assess several anthropometric and metabolic criteria.

PMID- 19840385
TI  - Large introns in relation to alternative splicing and gene evolution: a case
      study of Drosophila bruno-3.
AB  - BACKGROUND: Alternative splicing (AS) of maturing mRNA can generate structurally
      and functionally distinct transcripts from the same gene. Recent bioinformatic
      analyses of available genome databases inferred a positive correlation between
      intron length and AS. To study the interplay between intron length and AS
      empirically and in more detail, we analyzed the diversity of alternatively
      spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene.
      This gene was known to encode thirteen exons separated by introns of diverse
      sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's
      structure is expected to be conducive to AS, only two ASTs of this gene were
      previously described. RESULTS: Cloning of RT-PCR products of the entire ORF from
      four species representing three diverged Drosophila lineages provided an
      evolutionary perspective, high sensitivity, and long-range contiguity of splice
      choices currently unattainable by high-throughput methods. Consequently, we
      identified three new exons, a new exon fragment and thirty-three previously
      unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the
      exons surrounded by introns of at least 800 nucleotides, whereas exons split by
      introns of less than 250 nucleotides were always spliced contiguously in mRNA.
      Cases of exon loss and creation during Bru-3 evolution in Drosophila were also
      localized within large introns. Notably, we identified a true de novo exon gain:
      exon 8 was created along the lineage of the obscura group from intronic sequence
      between cryptic splice sites conserved among all Drosophila species surveyed.
      Exon 8 was included in mature mRNA by the species representing all the major
      branches of the obscura group. To our knowledge, the origin of exon 8 is the
      first documented case of exonization of intronic sequence outside vertebrates.
      CONCLUSION: We found that large introns can promote AS via exon-skipping and exon
      turnover during evolution likely due to frequent errors in their removal from
      maturing mRNA. Large introns could be a reservoir of genetic diversity, because
      they have a greater number of mutable sites than short introns. Taken together,
      gene structure can constrain and/or promote gene evolution.

PMID- 19840387
TI  - Animal models for clinical and gestational diabetes: maternal and fetal outcomes.
AB  - BACKGROUND: Diabetes in pregnant women is associated with an increased risk of
      maternal and neonatal morbidity and remains a significant medical challenge.
      Diabetes during pregnancy may be divided into clinical diabetes and gestational
      diabetes. Experimental models are developed with the purpose of enhancing
      understanding of the pathophysiological mechanisms of diseases that affect
      humans. With regard to diabetes in pregnancy, experimental findings from models
      will lead to the development of treatment strategies to maintain a normal
      metabolic intrauterine milieu, improving perinatal development by preventing
      fetal growth restriction or macrosomia. Based on animal models of diabetes during
      pregnancy previously reported in the medical literature, the present study aimed
      to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and
      mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal
      reproductive and fetal outcomes of Wistar rats to evaluate whether the animal
      model reproduces the maternal and perinatal results of clinical and gestational
      diabetes in humans. METHODS: On day 5 of life, 96 female Wistar rats were
      assigned to three experimental groups: control (n = 16), severe (n = 50) and mild
      diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy,
      rats were killed and their uterine horns were exposed to count implantation and
      fetus numbers to determine pre- and post-implantation loss rates. The fetuses
      were classified according to their birth weight. RESULTS: Severe and mild
      diabetic dams showed different glycemic responses during pregnancy, impairing
      fetal glycemia and weight, confirming that maternal glycemia is directly
      associated with fetal development. Newborns from severe diabetic mothers
      presented growth restriction, but mild diabetic mothers were not associated with
      an increased rate of macrosomic fetuses. CONCLUSION: Experimental models of
      severe diabetes during pregnancy reproduced maternal and fetal outcomes of
      pregnant women presenting uncontrolled clinical diabetes. On the other hand, the
      mild diabetes model caused mild hyperglycemia during pregnancy, although it was
      not enough to reproduce the increased rate of macrosomic fetuses seen in women
      with gestational diabetes.

PMID- 19840388
TI  - Ser170 of Bacillus thuringiensis Cry1Ab delta-endotoxin becomes anchored in a
      hydrophobic moiety upon insertion of this protein into Manduca sexta brush border
      membranes.
AB  - BACKGROUND: Three spin-labeled mutant proteins, mutated at the beginning, middle,
      and end of alpha-helix 5 of the Bacillus thuringiensis Cry1Ab delta-endotoxin,
      were used to study the involvement of these specific amino acid residues in ion
      transport and to determine conformational changes in the vicinity of these
      residues when the protein was translocated into a biological membrane. RESULTS:
      Amino acid residue leucine 157, located in the N-terminal portion of alpha-helix
      5, showed no involvement in ion transport, and the environment that surrounds the
      residue did not show any change when transferred into the biological membrane.
      Serine 170, located in the middle of the alpha-helix, showed no involvement in
      ion transport, but our findings indicate that in the membrane-bound state this
      residue faces an environment that makes the spin less mobile, as opposed to the
      mobility observed in an aqueous environment. Serine 176, located in the C
      terminal end of the alpha-helix 5 is shown to be involved in ion transport
      activity. CONCLUSION: Ion transport data for L157, S170, and S176, along with the
      mobility of the spin-labels, structural characterization of the resulting
      proteins, and toxicity assays against a target insect, suggest that the toxin
      undergoes conformational changes upon protein translocation into the midgut
      membrane. These conformational changes result in the midregion of the alpha-helix
      5 being exposed to a hydrophobic-like environment. The location of these three
      residues in the toxin suggests that the entire alpha-helix becomes inserted in
      the insect midgut membrane.

PMID- 19840390
TI  - Ergonomic assessment of the posture of surgeons performing endoscopic
      transurethral resections in urology.
AB  - BACKGROUND: During transurethral endoscopic prostate and bladder operations the
      influence of an ergonomic redesign of the arrangement of the operation equipment 
      including the introduction of a video-assisted resection method ('monitor
      endoscopy') instead of directly viewing onto the operation area via the endoscope
      ('direct endoscopy') - was studied with respect to the postures of the surgeons.
      METHODS: Postures were analysed on the basis of video recordings of the surgeons
      performed in the operation theatre during live operations and subsequent visual
      posture estimation executed by an observer. In particular, head, trunk and arm
      positions were assigned to posture categories according to a newly developed
      posture classification schema. 10 urological operations with direct endoscopy and
      9 with monitor endoscopy were included. RESULTS: Application of direct endoscopy
      coincides with distinct lateral and sagittal trunk and head inclinations, trunk
      torsion and strong forearm and upper arm elevations of the surgeons whereas
      operations with monitor endoscopy were performed with an almost upright head and
      trunk and hanging arms. The disadvantageous postures observed during direct
      endoscopy are mainly caused by the necessity to hold the endoscope continuously
      in close contact with the eye. CONCLUSION: From an ergonomic point of view,
      application of the video-assisted resection method should be preferred in
      transurethral endoscopic operations in order to prevent awkward postures of the
      surgeons and to limit muscular strain and fatigue. Furthermore, the application
      of the monitor method enables the use of a chair equipped with back support and
      armrests and benefits the reduction of postural stress.

PMID- 19840389
TI  - Identification of a haplotype block in the 5q31 cytokine gene cluster associated
      with the susceptibility to severe malaria.
AB  - BACKGROUND: It has been previously demonstrated that a single nucleotide
      polymorphism (SNP) in the IL13 promoter region, IL13 -1055T>C (rs1800925), was
      associated with susceptibility to severe malaria in Thais. In the present study,
      fine association mapping for a cytokine gene cluster including IL4, IL5, and IL13
      on chromosome 5q31 was conducted using the same malaria subjects to refine the
      region containing a primary variant or a haplotype susceptible to severe malaria.
      METHODS: A total of 82 SNPs spanning 522 kb of the 5q31 region were analysed in
      368 patients with Plasmodium falciparum malaria (203 mild malaria and 165 severe
      malaria patients). RESULTS: Only rs1881457 located in the promoter region of
      IL13, which is in linkage disequilibrium with rs1800925 (r2 = 0.73), showed a
      significant association with severe malaria after adjusting for multiple testing
      (P = 0.046 by permutation test). This SNP was in a haplotype block spanning 97 kb
      (from rs2069812 to rs2240032). The detected haplotype block contained the RAD50
      gene and the promoter of IL13, but not the other genes. CONCLUSION: A haplotype
      block in which a primary polymorphism associated with severe malaria is likely to
      be encoded was identified in Thai malaria patients.

PMID- 19840391
TI  - Breaking the hierarchy--a new cluster selection mechanism for hierarchical
      clustering methods.
AB  - BACKGROUND: Hierarchical clustering methods like Ward's method have been used
      since decades to understand biological and chemical data sets. In order to get a
      partition of the data set, it is necessary to choose an optimal level of the
      hierarchy by a so-called level selection algorithm. In 2005, a new kind of
      hierarchical clustering method was introduced by Palla et al. that differs in two
      ways from Ward's method: it can be used on data on which no full similarity
      matrix is defined and it can produce overlapping clusters, i.e., allow for
      multiple membership of items in clusters. These features are optimal for
      biological and chemical data sets but until now no level selection algorithm has
      been published for this method. RESULTS: In this article we provide a general
      selection scheme, the level independent clustering selection method, called
      LInCS. With it, clusters can be selected from any level in quadratic time with
      respect to the number of clusters. Since hierarchically clustered data is not
      necessarily associated with a similarity measure, the selection is based on a
      graph theoretic notion of cohesive clusters. We present results of our method on
      two data sets, a set of drug like molecules and set of protein-protein
      interaction (PPI) data. In both cases the method provides a clustering with very
      good sensitivity and specificity values according to a given reference
      clustering. Moreover, we can show for the PPI data set that our graph theoretic
      cohesiveness measure indeed chooses biologically homogeneous clusters and
      disregards inhomogeneous ones in most cases. We finally discuss how the method
      can be generalized to other hierarchical clustering methods to allow for a level
      independent cluster selection. CONCLUSION: Using our new cluster selection method
      together with the method by Palla et al. provides a new interesting clustering
      mechanism that allows to compute overlapping clusters, which is especially
      valuable for biological and chemical data sets.

PMID- 19840392
TI  - Immune control of HIV-1 infection after therapy interruption: immediate versus
      deferred antiretroviral therapy.
AB  - BACKGROUND: The optimal stage for initiating antiretroviral therapies in HIV-1
      bearing patients is still a matter of debate. METHODS: We present computer
      simulations of HIV-1 infection aimed at identifying the pro et contra of
      immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART).
      RESULTS: Our simulations highlight that a prompt specific CD8+ cytotoxic T
      lymphocytes response is detected when therapy is delayed. Compared to very early
      initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate
      the decline of viremia in a shorter time and, at interruption of therapy, the
      virus experiences a stronger immune pressure. We also observe, however, that the
      immunological effects of the therapy fade with time in both therapeutic regimens.
      Thus, within one year from discontinuation, viral burden recovers to the value at
      which it would level off in the absence of therapy.In summary, simulations show
      that immediate therapy does not prolong the disease-free period and does not
      confer a survival benefit when compared to treatment started during the chronic
      infection phase. CONCLUSION: Our conclusion is that, since there is no therapy to
      date that guarantees life-long protection, deferral of therapy should be
      preferred in order to minimize the risk of adverse effects, the occurrence of
      drug resistances and the costs of treatment.

PMID- 19840393
TI  - Generational status and duration of residence predict diabetes prevalence among
      Latinos: the California Men's Health Study.
AB  - BACKGROUND: Diabetes disproportionately affects Latinos. However, examining
      Latinos as one group obscures important intra-group differences. This study
      examined how generational status, duration of US residence, and language
      preference are associated with diabetes prevalence and to what extent these
      explain the higher prevalence among Latinos. METHODS: We determined nativity,
      duration of US residence, language preference, and diabetes prevalence among 11
      817 Latino, 6109 black, and 52 184 white participants in the California Men's
      Health Study. We combined generational status and residence duration into a
      single migration status variable with levels: > or = third generation; second
      generation; and immigrant living in the US for > 25, 16-25, 11-15, or < or = 10
      years. Language preference was defined as language in which the participant took
      the survey. Logistic regression models were specified to assess the associations
      of dependent variables with prevalent diabetes. RESULTS: Diabetes prevalence was
      22%, 23%, and 11% among Latinos, blacks, and whites, respectively. In age
      adjusted models, we observed a gradient of risk of diabetes by migration status
      among Latinos. Further adjustment for socioeconomic status, obesity and health
      behaviors only partially attenuated this gradient. Language preference was a weak
      predictor of prevalent diabetes in some models and not significant in others. In
      multivariate models, we found that odds of diabetes were higher among US-born
      Latinos than US-born blacks. CONCLUSION: Generational status and residence
      duration were associated with diabetes prevalence among middle-aged Latino men in
      California. As the Latino population grows, the burden of diabetes-associated
      disease is likely to increase and demands public health attention.

PMID- 19840394
TI  - Surveillance indicators for potential reduced exposure products (PREPs):
      developing survey items to measure awareness.
AB  - BACKGROUND: Over the past decade, tobacco companies have introduced cigarettes
      and smokeless tobacco products (known as Potential Reduced Exposure Products,
      PREPs) with purportedly lower levels of some toxins than conventional cigarettes
      and smokeless products. It is essential that public health agencies monitor
      awareness, interest, use, and perceptions of these products so that their impact
      on population health can be detected at the earliest stages. METHODS: This paper
      reviews and critiques existing strategies for measuring awareness of PREPs from
      16 published and unpublished studies. From these measures, we developed new
      surveillance items and subjected them to two rounds of cognitive testing, a
      common and accepted method for evaluating questionnaire wording. RESULTS: Our
      review suggests that high levels of awareness of PREPs reported in some studies
      are likely to be inaccurate. Two likely sources of inaccuracy in awareness
      measures were identified: 1) the tendency of respondents to misclassify "no
      additive" and "natural" cigarettes as PREPs and 2) the tendency of respondents to
      mistakenly report awareness as a result of confusion between PREPs brands and
      similarly named familiar products, for example, Eclipse chewing gum and Accord
      automobiles. CONCLUSION: After evaluating new measures with cognitive interviews,
      we conclude that as of winter 2006, awareness of reduced exposure products among
      U.S. smokers was likely to be between 1% and 8%, with the higher estimates for
      some products occurring in test markets. Recommended measurement strategies for
      future surveys are presented.

PMID- 19840395
TI  - Ruminal acidosis and the rapid onset of ruminal parakeratosis in a mature dairy
      cow: a case report.
AB  - A mature dairy cow was transitioned from a high forage (100% forage) to a high
      grain (79% grain) diet over seven days. Continuous ruminal pH recordings were
      utilized to diagnose the severity of ruminal acidosis. Additionally, blood and
      rumen papillae biopsies were collected to describe the structural and functional
      adaptations of the rumen epithelium. On the final day of the grain challenge, the
      daily mean ruminal pH was 5.41+/-0.09 with a minimum of 4.89 and a maximum of
      6.31. Ruminal pH was under 5.0 for 130 minutes (2.17 hours) which is
      characterized as the acute form of ruminal acidosis in cattle. The grain
      challenge increased blood beta-hydroxybutyrate by 1.8 times and rumen papillae
      mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A synthase by 1.6 times.
      Ultrastructural and histological adaptations of the rumen epithelium were imaged
      by scanning electron and light microscopy. Rumen papillae from the high grain
      diet displayed extensive sloughing of the stratum corneum and compromised cell
      adhesion as large gaps were apparent between cells throughout the strata. This
      case report represents a rare documentation of how the rumen epithelium alters
      its function and structure during the initial stage of acute acidosis.

PMID- 19840396
TI  - Plasma protein C levels in immunocompromised septic patients are significantly
      lower than immunocompetent septic patients: a prospective cohort study.
AB  - INTRODUCTION: Activated Protein C [APC] improves outcome in immunocompetent
      patients with severe sepsis particularly in those who are perceived to have high
      mortality risk. Before embarking on a trial of APC administration in
      immunocompromised septic patients, a preliminary study on plasma levels of
      protein C in this cohort is essential. OBJECTIVE: To assess serum Protein C
      concentrations in immunocompromised patients as compared to immunocompetent
      patients during sepsis, severe sepsis, septic shock and recovery. METHODS:
      Prospective cohort study in a tertiary hospital. Patients satisfying inclusion
      criteria were enrolled after informed consent. Clinical variables were noted with
      sample collection when patients met criteria for sepsis, severe sepsis, septic
      shock and recovery. Protein C levels were measured using monoclonal antibody
      based fluorescence immunoassay. RESULTS: Thirty one patients participated in this
      study (22 immunocompromised, 9 immunocompetent). Protein C levels were found to
      be significantly lower in the immunocompromised group compared to the
      immunocompetent group, particularly observed in severe sepsis [2.27 (95% CI: 1.63
      2.9) vs 4.19 (95% CI: 2.87-5.52) mcg/ml] (p = 0.01) and sepsis [2.59 (95% CI:
      1.98-3.21) vs 3.64 (95% CI: 2.83-4.45) mcg/ml] (p = 0.03). SOFA scores were
      similar in both the groups across sepsis, severe sepsis and septic shock
      categories. Protein C levels improved significantly in recovery (p = 0.001)
      irrespective of immune status. CONCLUSION: Protein C levels were significantly
      lower in immunocompromised patients when compared to immunocompetent patients in
      severe sepsis and sepsis categories. Our study suggests a plausible role for APC
      in severely septic immunocompromised patients which need further elucidation.

PMID- 19840397
TI  - Statin prophylaxis and inflammatory mediators following cardiopulmonary bypass: a
      systematic review.
AB  - INTRODUCTION: Induction of an inflammatory response is thought to have a
      significant role in the complications that follow cardiopulmonary bypass (CPB).
      The statin drugs are increasingly being recognized as having potent anti
      inflammatory effects and hence have potential to influence an important mechanism
      of injury in CPB, although there is no current confirmation that this is indeed
      the case. Our objective was to systematically review if pre-operative
      prophylactic statin therapy, compared with placebo or standard of care, can
      decrease the inflammatory response in people undergoing heart surgery with CPB.
      METHODS: We performed a systematic and comprehensive literature search for all
      randomized controlled trials (RCTs) of open heart surgery with CPB in adults or
      children who received prophylactic statin treatment prior to CPB, with reported
      outcomes which included markers of inflammation. Two authors independently
      identified eligible studies, extracted data, and assessed study quality using
      standardized instruments. Weighted mean difference (WMD) was the primary summary
      statistic with data pooled using a random effects model. Descriptive analysis was
      used when data could not be pooled. RESULTS: Eight RCTs were included in the
      review, with the number of trials for each inflammatory outcome being even more
      limited. Pooled data demonstrated benefit with the use of statin to attenuate the
      post-CPB increase in interleukins 6 and 8 (IL-6, IL-8), peak high sensitivity C
      reactive protein (hsCRP), and tumor necrosis factor-alpha (TNF-alpha) post-CPB
      (WMD [95% confidence interval (CI)] -23.5 pg/ml [-36.6 to -10.5]; -23.4 pg/ml [
      35.8 to -11.0]; -15.3 mg/L [CI -26.9 to -3.7]; -2.10 pg/ml [-3.83 to -0.37]
      respectively). Very limited RCT evidence suggests that prophylactic statin
      therapy may also decrease adhesion molecules following CPB including neutrophil
      CD11b and soluble P (sP)-selectin. CONCLUSIONS: Although the RCT evidence may
      suggest a reduction in post-CPB inflammation by statin therapy, the evidence is
      not definitive due to significant limitations. Several of the trials were not
      methodologically rigorous and statin intervention was highly variable in this
      small number of studies. This systematic review demonstrates that there is a
      significant gap that exists in the current literature in regards to the potential
      anti-inflammatory effect of statin therapy prior to CPB.

PMID- 19840398
TI  - The infective cycle of Cabbage leaf curl virus (CaLCuV) is affected by CRUMPLED
      LEAF (CRL) gene in Arabidopsis thaliana.
AB  - BACKGROUND: Geminiviruses are single-stranded DNA viruses that cause serious crop
      losses worldwide. Successful infection by these pathogens depends extensively on
      virus-host intermolecular interactions that allow them to express their gene
      products, to replicate their genomes and to move to adjacent cells and throughout
      the plant. RESULTS: To identify host genes that show an altered regulation in
      response to Cabbage leaf curl virus (CaLCuV) infection, a screening of
      transposant Arabidopsis thaliana lines was carried out. Several genes were
      identified to be virus responsive and one, Crumpled leaf (CRL) gene, was selected
      for further characterization. CRL was previously reported by Asano et al., (2004)
      to affect the morphogenesis of all plant organs and the division of plastids. We
      report here that CRL expression, during CaLCuV infection, shows a short but
      strong induction at an early stage (3-5 days post inoculation, dpi). To study the
      role of CRL in CaLCuV infection, CRL over-expressing and silenced transgenic
      plants were generated. We compared the replication, movement and infectivity of
      CaLCuV in transgenic and wild type plants. CONCLUSION: Our results showed that
      CRL over-expressing plants showed an increased susceptibility to CaLCuV infection
      (as compared to wt plants) whereas CRL-silenced plants, on the contrary,
      presented a reduced susceptibility to viral infection. The possible role of CRL
      in the CaLCuV infection cycle is discussed.

PMID- 19840399
TI  - Dietary supplementation by older adults in southern China: a hospital outpatient
      clinic study.
AB  - BACKGROUND: There has been little knowledge about dietary supplementation by the
      Chinese elderly. The aim of this cross-sectional study was to investigate the
      usage of dietary supplements by older adults in southern China. METHODS: A total
      of 600 community-dwelling older adults were recruited from the outpatient clinics
      of three major hospitals in Foshan city between July 2007 and July 2008. Face-to
      face interviews of participants were conducted to obtain information on
      demographics, lifestyle and dietary supplements use. Frequency and duration of
      usage were recorded for six categories of dietary supplements. RESULTS: Among the
      446 consented participants (241 men and 205 women) who were over 55 years of age,
      19.1% consumed one or more types of dietary supplements. The prevalence of usage
      was significantly higher (p = 0.008) for females (24.4%) than for males (14.5%).
      Dietary supplements were more likely to be consumed by non-smokers (p = 0.021)
      and those with hyperlipidemia (p = 0.003). The most popular supplement among
      users was calcium (53%). The majority (71%) of the users consumed supplements on
      a regular basis at one or more times per day, with an average duration of 2.95
      (SD 4.80) years. CONCLUSION: The overall prevalence of dietary supplementation in
      this older Chinese population was considerably lower than those in other Asia
      Pacific countries.

PMID- 19840400
TI  - Effectiveness of strategies to encourage general practitioners to accept an offer
      of free access to online evidence-based information: a randomised controlled
      trial.
AB  - BACKGROUND: This study examined the effectiveness of seven different
      interventions designed to increase the proportion of general practitioners (GPs)
      accepting an offer of free access to an online evidence-based resource. METHODS:
      Australian GPs (n = 14,000) were randomly selected and assigned to seven
      intervention groups, with each receiving a different letter. Seven different
      strategies were used to encourage GPs to accept an offer of two years free access
      to an online evidence-based resource (BMJ Clinical Evidence). The first group
      received a standard letter of offer with no experimental demands. Groups two to
      seven received a standard letter of offer outlining the requirements of the
      study. They were asked to complete an initial online questionnaire, agree to
      complete a 12-month follow-up questionnaire, and agree to having data about their
      usage of the online evidence-based resource provided to researchers. Groups three
      to seven also had additional interventions included in the letter of offer:
      access to an online tutorial in use of the resource (group three); provision of a
      pamphlet with statements from influential opinion leaders endorsing the resource
      (group four); offer of eligibility to receive professional development points
      (group five); offer of eligibility for a prize of $500 for registration at a
      medical conference of their choice (group six); and a combination of some of the
      above interventions (group seven). RESULTS: In the group with no research
      demands, 27% accepted the offer. Average acceptance across all other groups was
      10%. There was no advantage in using additional strategies such as financial
      incentives, opinion leader support, offer of professional development points, or
      an educational aid over a standard letter of offer to increase acceptance rates.
      CONCLUSION: This study showed low acceptance rates of the offer of access to the
      online resource when there was an associated requirement of response to a short
      online questionnaire and non-obtrusive monitoring of GP behaviour in terms of
      accessing the resource. If we are to improve care and encourage evidence-based
      practice, we need to find effective ways of motivating doctors and other health
      professionals to take part in research that can inform our implementation
      efforts.

PMID- 19840401
TI  - Sampling nucleotide diversity in cotton.
AB  - BACKGROUND: Cultivated cotton is an annual fiber crop derived mainly from two
      perennial species, Gossypium hirsutum L. or upland cotton, and G. barbadense L.,
      extra long-staple fiber Pima or Egyptian cotton. These two cultivated species are
      among five allotetraploid species presumably derived monophyletically between G.
      arboreum and G. raimondii. Genomic-based approaches have been hindered by the
      limited variation within species. Yet, population-based methods are being used
      for genome-wide introgression of novel alleles from G. mustelinum and G.
      tomentosum into G. hirsutum using combinations of backcrossing, selfing, and
      inter-mating. Recombinant inbred line populations between genetics standards TM
      1, (G. hirsutum) x 3-79 (G. barbadense) have been developed to allow high-density
      genetic mapping of traits. RESULTS: This paper describes a strategy to
      efficiently characterize genomic variation (SNPs and indels) within and among
      cotton species. Over 1000 SNPs from 270 loci and 279 indels from 92 loci
      segregating in G. hirsutum and G. barbadense were genotyped across a standard
      panel of 24 lines, 16 of which are elite cotton breeding lines and 8 mapping
      parents of populations from six cotton species. Over 200 loci were genetically
      mapped in a core mapping population derived from TM-1 and 3-79 and in G. hirsutum
      breeding germplasm. CONCLUSION: In this research, SNP and indel diversity is
      characterized for 270 single-copy polymorphic loci in cotton. A strategy for SNP
      discovery is defined to pre-screen loci for copy number and polymorphism. Our
      data indicate that the A and D genomes in both diploid and tetraploid cotton
      remain distinct from each such that paralogs can be distinguished. This research
      provides mapped DNA markers for intra-specific crosses and introgression of
      exotic germplasm in cotton.

PMID- 19840403
TI  - Genetic effect of CysLTR2 polymorphisms on its mRNA synthesis and stabilization.
AB  - BACKGROUND: We previously demonstrated that single nucleotide polymorphism (SNP)
      and haplotypes were associated with aspirin hypersensitivity in asthmatics. We
      investigated the genetic effects of the SNPs and haplotypes on the expression of
      the CysLTR2 gene. METHODS: We measured CysLTR2 protein and mRNA expression in EB
      virus-infected B cell lines from asthmatics having ht1+/+ and ht2+/+. A gel
      retardation assay was used to identify nuclear protein binding to the c.-819
      promoter site. The function of promoter and 3'-UTR were assessed using pGL3
      luciferase and pEGFP reporter system, respectively. RESULTS: We found that the
      expression of CysLTR2 protein was higher in B cell lines of asthmatics having
      ht2+/+ than in those having ht1+/+. PMA/ionomycin induced higher mRNA expression
      of CysLTR2 in B cell lines from ht2+/+ asthmatics than those from ht1+/+
      asthmatics. A nuclear protein from the B cell lines showed stronger DNA binding
      affinity with a probe containing c.-819T than one containing c.-819G. The
      luciferase activity of the c.-819T type of CysLTR2 promoter was higher than that
      of the c.-819G type. EGFP expression was higher in the EGFP-c.2078T 3'-UTR fusion
      construct than in the c.2078C construct. CONCLUSION: The sequence variants of
      CysLTR2 may affect its transcription and the stability of its mRNA, resulting in
      altered expression of CysLTR2 protein, which in turn causes some asthmatics to be
      susceptible to aspirin hypersensitivity.

PMID- 19840402
TI  - Ras promotes cell survival by antagonizing both JNK and Hid signals in the
      Drosophila eye.
AB  - BACKGROUND: Programmed cell death, or apoptosis, is a fundamental physiological
      process during normal development or in pathological conditions. The activation
      of apoptosis can be elicited by numerous signalling pathways. Ras is known to
      mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye.
      Here we report the isolation of a new loss-of-function ras allele, rasKP, which
      causes excessive apoptosis in the Drosophila eye. RESULTS: This new function is
      likely to be mediated through the JNK pathway since the inhibition of JNK
      signalling can significantly suppress rasKP-induced apoptosis, whereas the
      removal of hid only weakly suppresses the phenotype. Furthermore, the reduction
      of JNK signalling together with the expression of the baculovirus caspase
      inhibitor p35, which blocks Hid activity, strongly suppresses the rasKP cell
      death. In addition, we find a strong correlation between rasKP-induced apoptosis
      in the eye disc and the activation of JNK signalling. CONCLUSION: In the
      Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and
      Hid activities. Surprisingly, reducing Ras activity in the wing, however, does
      not cause apoptosis but rather affects cell and organ size. Thus, in addition to
      its requirement for cell viability, Ras appears to mediate different biological
      roles depending on the developmental context and on the level of its expression.

PMID- 19840404
TI  - Rat model of metastatic breast cancer monitored by MRI at 3 tesla and
      bioluminescence imaging with histological correlation.
AB  - BACKGROUND: Establishing a large rodent model of brain metastasis that can be
      monitored using clinically relevant magnetic resonance imaging (MRI) techniques
      is challenging. Non-invasive imaging of brain metastasis in mice usually requires
      high field strength MR units and long imaging acquisition times. Using the brain
      seeking MDA-MB-231BR transfected with luciferase gene, a metastatic breast cancer
      brain tumor model was investigated in the nude rat. Serial MRI and
      bioluminescence imaging (BLI) was performed and findings were correlated with
      histology. Results demonstrated the utility of multimodality imaging in
      identifying unexpected sights of metastasis and monitoring the progression of
      disease in the nude rat. METHODS: Brain seeking breast cancer cells MDA-MB-231BR
      transfected with firefly luciferase (231BRL) were labeled with ferumoxides
      protamine sulfate (FEPro) and 1-3 x 106 cells were intracardiac (IC) injected.
      MRI and BLI were performed up to 4 weeks to monitor the early breast cancer cell
      infiltration into the brain and formation of metastases. Rats were euthanized at
      different time points and the imaging findings were correlated with histological
      analysis to validate the presence of metastases in tissues. RESULTS: Early
      metastasis of the FEPro labeled 231BRL were demonstrated on T2*-weighted MRI and
      BLI within 1 week post IC injection of cells. Micro-metastatic tumors were
      detected in the brain on T2-weighted MRI as early as 2 weeks post-injection in
      greater than 85% of rats. Unexpected skeletal metastases from the 231BRL cells
      were demonstrated and validated by multimodal imaging. Brain metastases were
      clearly visible on T2 weighted MRI by 3-4 weeks post infusion of 231BRL cells,
      however BLI did not demonstrate photon flux activity originating from the brain
      in all animals due to scattering of the photons from tumors. CONCLUSION: A model
      of metastatic breast cancer in the nude rat was successfully developed and
      evaluated using multimodal imaging including MRI and BLI providing the ability to
      study the temporal and spatial distribution of metastases in the brain and
      skeleton.

PMID- 19840405
TI  - Highlights from the 5th International Society for Computational Biology Student
      Council Symposium at the 17th Annual International Conference on Intelligent
      Systems for Molecular Biology and the 8th European Conference on Computational
      Biology.

PMID- 19840420
TI  - Effects of oats on plasma cholesterol and lipoproteins in C57BL/6 mice are
      substrain specific.
AB  - Cholesterol-lowering effects of oats have been demonstrated in both animals and
      human subjects. However, the crucial properties of oat-containing diets that
      determine their health effects need to be further investigated to optimise their
      use. A mouse model would be a valuable tool, but few such studies have been
      published to date. We investigated the effects of oat bran on plasma cholesterol
      and lipoproteins in two substrains of C57BL/6 mice. Western diet was made
      atherogenic by the addition of 0.8 % cholesterol and 0.1 % cholic acid. After 4
      weeks on atherogenic diet, total plasma cholesterol had increased from 1.86-2.53
      to 3.77-4.40 mmol/l. In C57BL/6NCrl mice, inclusion of 27 and 40 % oat bran
      reduced total plasma cholesterol by 19 and 24 %, respectively, reduced the shift
      from HDL to LDL+VLDL and caused increased faecal cholesterol excretion. There was
      no effect of oat bran on plasma levels of the inflammatory markers fibrinogen,
      serum amyloid A or TNF-alpha. Contrary to findings in C57BL/6NCrl mice, there was
      no sustained effect of oat bran (27 or 40 %) on plasma cholesterol in
      C57BL/6JBomTac mice after 4 weeks of feeding. Thus, C57BL/6NCrl mice fed an
      atherogenic diet are a good model for studies of physiological effects of oats,
      whereas a substrain derived from C57BL/6J, raised in a different breeding
      environment and likely possessing functional genetic differences from C57BL/6N,
      is considerably less responsive to oats. The present finding that two substrains
      of mice respond differently to oats is of practical value, but can also help to
      elucidate mechanisms of the cholesterol-lowering effect of oats.

PMID- 19840421
TI  - Assessing dietary intake in a population undergoing a rapid transition in diet
      and lifestyle: the Arctic Inuit in Nunavut, Canada.
AB  - The aims of the present study were to (1) characterise the diets of adult Inuit;
      (2) highlight foods for a nutritional and lifestyle intervention programme; (3)
      develop a quantitative FFQ (QFFQ) to evaluate the programme and monitor changes
      in dietary intake in this population over time. A dietary survey using single 24
      h dietary recalls was conducted among Inuit aged between 19 and 87 years in two
      communities in Nunavut, Canada. Eighty-seven subjects completed the recalls
      (response rate was approximately 73 %). The mean energy intake for men and women
      was 9530 and 6939 kJ, respectively. The intakes of dietary fibre and the majority
      of vitamins and minerals (especially vitamins A, D, and E, total folate and Ca)
      were far below the recommendations. Traditional foods contributed 40 and 42 %,
      respectively, to protein and Fe intakes. Non-nutrient-dense store-bought foods
      were consumed much more frequently than the nutrient-dense traditional foods.
      Foods high in fat and sugar were highlighted, and will be replaced by healthier,
      more nutrient-dense alternatives to address the dietary inadequacies for the
      nutritional intervention programme. A 154-item QFFQ was developed and pilot
      tested in the Arctic Inuit. The present study highlighted foods to be targeted
      for a nutritional and lifestyle intervention programme not previously undertaken
      in this population. This QFFQ is culturally appropriate and specific for
      evaluating the effectiveness of the programme, as well as monitoring nutritional
      transition in this population.

PMID- 19840422
TI  - Ossifying fibromyxoid tumour of the sphenoid sinus.
AB  - INTRODUCTION: Ossifying fibromyxoid tumour is a recently described, rare but
      morphologically distinctive soft tissue neoplasm characterised by a combination
      of myxoid and/or fibrous stroma with areas of ossification. Although most authors
      postulate a neuroectodermal origin for this peculiar tumour, there is no
      agreement in the literature regarding its histopathogenesis. To our knowledge,
      this is the first reported case of ossifying fibromyxoid tumour involving the
      sphenoid sinus. HISTOLOGICAL FINDINGS: Tumour of low cell density, composed of
      small, spindle-shaped or stellate cells with small, irregular nuclei set in a
      fibromyxoid stroma. MANAGEMENT: Following discussion at the skull base
      multidisciplinary team meeting, a combined surgical team including an
      otorhinolaryngologist and a neurosurgeon carried out resection of the lesion,
      using an endoscopic transnasal approach, followed by reconstruction of the
      defect. CONCLUSIONS: An awareness of the distinctive histopathological features
      of ossifying fibromyxoid tumour, and of its clinical effects, is crucial to
      establishing a definitive diagnosis and thereby instituting appropriate
      management. This case report also reinforces the evolving role of the endoscopic
      transnasal approach in the management of inflammatory and neoplastic disease
      involving the skull base. This is increasingly being made possible by close
      collaboration between multiple surgical specialties, including
      otorhinolaryngology and neurosurgery.

PMID- 19840423
TI  - Radiologically guided balloon dilatation of neopharyngeal strictures following
      total laryngectomy and pharyngolaryngectomy: 21 years' experience.
AB  - OBJECTIVE: To assess the efficacy of radiologically guided balloon dilatation for
      the treatment of dysphagia secondary to neopharyngeal strictures in patients who
      have undergone laryngectomy. STUDY DESIGN: Retrospective case series. SUBJECTS
      AND METHODS: Twenty consecutive patients with pharyngeal stricture and dysphagia
      following total laryngectomy or pharyngolaryngectomy. Patients underwent balloon
      dilatation of the stricture under radiological guidance. The main outcome measure
      was maintenance of swallowing. RESULTS: Five patients gained relief of their
      dysphagia with one balloon dilatation only. Nine patients required more than one
      dilatation to maintain swallowing. Two patients had balloon dilatation procedures
      and stent insertion for palliative relief of dysphagia from known recurrent
      malignant disease. Three patients failed to maintain swallowing with repeat
      dilatations. No patients suffered any significant complications such as
      perforation. CONCLUSIONS: Radiologically guided balloon dilatation is minimally
      invasive and safe. It is well tolerated. It may be repeated frequently, and can
      successfully relieve pharyngeal strictures in patients who have undergone total
      laryngectomy or pharyngolaryngectomy.

PMID- 19840424
TI  - Sweet's disease and profound, bilateral, sensorineural hearing loss.
AB  - OBJECTIVE: We report a case of Sweet's disease associated with rapid, profound
      loss of hearing, against a background of progressive, bilateral, sensorineural
      hearing loss. RESULTS: The clinical features were indistinguishable from those of
      immune-mediated inner ear disease. Establishment of a definitive diagnosis was a
      challenge due to the absence of a reliable diagnostic test. The patient was
      unresponsive to extensive immunosuppressive therapy and subsequently underwent
      cochlear implantation, with good hearing outcomes. CONCLUSIONS: Profound,
      bilateral, sensorineural hearing loss in the context of Sweet's disease may be
      related to the underlying immunological aetiology. Cochlear implantation can
      successfully restore hearing when immunotherapy fails.

PMID- 19840425
TI  - Carbon dioxide laser cordectomy for verrucous carcinoma of vocal folds.
AB  - BACKGROUND: Verrucous carcinoma occurs infrequently in the vocal folds. This
      tumour has an excellent prognosis with proper treatment. Management strategies
      include surgery, radiotherapy or both. AIM: To evaluate the long-term results of
      type I and II laser cordectomy for the treatment of verrucous carcinoma of the
      vocal folds. MATERIALS AND METHODS: We reviewed the files of 18 patients with
      verrucous carcinoma of the vocal folds treated by type I or II laser cordectomy
      in our department from 1989 to 2006, and recorded clinical and outcome data.
      RESULTS: None of the patients had any major post-operative complications. All had
      a subjectively satisfactory quality of voice, with no morbidity. Patient follow
      up ranged from three to 228 months (mean, 48 months). Five patients were treated
      with post-operative radiotherapy for persistent disease, of whom four underwent
      repeated surgery due to recurrence. CONCLUSION: Type I or II laser cordectomy is
      a safe, feasible, secure method of treating verrucous carcinoma of the vocal
      folds. There were no major complications in our patient series. Most recurrent
      disease was manageable locally with repeated surgery.

PMID- 19840426
TI  - Prospective study of sensorineural hearing loss following radiotherapy for
      nasopharyngeal carcinoma.
AB  - OBJECTIVES: To investigate the severity and incidence of sensorineural hearing
      loss in patients with nasopharyngeal carcinoma treated with radiotherapy.
      METHODS: Forty-two patients with nasopharyngeal carcinoma were treated with
      conventional radiotherapy. Audiological testing was performed to compare
      patients' hearing before and at varying stages after radiotherapy. RESULTS: At
      one month post-radiation, a significant hearing threshold increase was seen only
      for high frequencies. At 12, 24 and 60 months post-radiation, significant
      threshold increases were observed at speech frequencies (4.0 and 8.0 kHz),
      compared with pre-radiation data. The mean values of wave I, III and V latencies
      and of the I-V interpeak latency intervals were not significantly altered at one
      month post-radiation, but were significantly prolonged at 12, 24 and 60 months
      post-radiation, compared with pre-radiation data. CONCLUSION: In patients with
      nasopharyngeal carcinoma treated with radiotherapy, the severity and incidence of
      radiation-induced sensorineural hearing loss increased with time, especially at
      high frequencies. This hearing impairment may be due to changes in the cochlea
      and/or the retrocochlear auditory pathway.

PMID- 19840427
TI  - Meningocoele of fallopian canal causing recurrent meningitis.
AB  - OBJECTIVE: We report a rare case of meningocoele of the fallopian canal resulting
      in recurrent meningitis. METHODS: We present a case report together with a review
      of the world literature concerning meningocoele of the fallopian canal and
      meningitis. RESULTS: A child developed profound, bilateral, sensorineural hearing
      loss as a result of meningitis caused by a meningocoele of the fallopian canal.
      He was treated with bilateral cochlear implantation, with a subtotal petrosectomy
      and middle ear and eustachian tube obliteration on the affected side. CONCLUSION:
      Meningocoele of the fallopian canal has rarely been reported. This lesion can
      present with recurrent meningitis and, rarely, with facial weakness. All children
      with recurrent meningitis should be investigated for skull base defects.
      Treatment aims to prevent further episodes of meningitis; we recommend that this
      is best achieved by the technique of subtotal petrosectomy, with obliteration of
      the middle ear and eustachian tube.

PMID- 19840428
TI  - Perforation after rigid pharyngo-oesophagoscopy: when do symptoms and signs
      develop?
AB  - BACKGROUND: Perforation after pharyngo-oesophagoscopy is a serious complication,
      and its identification, through close patient monitoring, is essential. Yet
      little is known about when symptoms and signs develop, and thus how long any
      close monitoring should last. AIM: To examine the timing of individual symptoms
      and signs of perforation after rigid pharyngo-oesophagoscopy. METHODOLOGY: Three
      centre, retrospective study. RESULTS: Of 3459 patients undergoing rigid pharyngo
      oesophagoscopy, 10 (0.29 per cent) developed perforations, nine of which were
      suspected intra-operatively. Symptoms and signs developed at 1.5 hours post
      operatively at the earliest, and at 36 hours at the latest. Three patients were
      asymptomatic. The majority of procedures (n = 8) were undertaken for food bolus
      obstruction or foreign body ingestion. CONCLUSION: Pharyngo-oesophagoscopy for
      food bolus obstruction and foreign body ingestion accounts for a large number of
      perforations, but symptoms and signs may take longer than 24 hours to develop. A
      contrast swallow should be considered in high risk patients, and a high index of
      suspicion maintained in order to detect this complication.

PMID- 19840429
TI  - Latent superior canal dehiscence syndrome unmasked by stapedotomy for
      otosclerosis.
AB  - OBJECTIVE: This report describes a novel case in which superior canal dehiscence
      syndrome was unmasked by successful stapes surgery for otosclerosis. METHODS:
      Case report and literature review regarding superior canal dehiscence syndrome.
      INTRODUCTION: Superior canal dehiscence syndrome is a rare but well described
      condition in which audiovestibular symptoms are caused by noise or straining. A
      dehiscence of the superior semicircular canal in the floor of the middle cranial
      fossa is responsible, and acts as a 'third window' into the inner ear. CASE
      HISTORY: A patient with confirmed otosclerosis underwent second-side stapedotomy,
      with good audiometric outcomes. Unfortunately, surgery was complicated by
      immediate post-operative vertigo and persistent auditory symptoms. A diagnosis of
      superior canal dehiscence syndrome was eventually made, on the basis of low
      threshold vestibular evoked myogenic potentials and characteristic computed
      tomography findings. Superior canal resurfacing resulted in complete resolution
      of symptoms. DISCUSSION: The otosclerotic focus in the oval window prevented the
      development of symptoms from this patient's superior canal dehiscence syndrome.
      Surgical stapedotomy created a third window and resulted in immediate post
      operative imbalance and auditory symptoms. CONCLUSION: The diagnosis of superior
      canal dehiscence syndrome should be considered in patients with persistent
      audiovestibular symptoms after stapes surgery. High resolution computed
      tomography of the temporal bone and vestibular evoked myogenic potential testing,
      if available, are the investigations of choice in confirming the diagnosis.

PMID- 19840430
TI  - Two new species of spiruroid nematodes in birds from Kangean Island, Indonesia.
AB  - Two new species of spiruroid nematodes in birds from Kangean Island, Indonesia
      are reported: Diplotriaena anthreptis sp. nov. is found from the abdominal cavity
      of Anthreptes malacensis malacensis. The new species is similar to D. ozouxi, D.
      bargusinica, D. delta, D. isabellina and D. obtusa in the size of tridents and
      the length of spicules. However, it differs from the five similar species in the
      structure of the tridents, in the morphology of the right spicule, in the spicule
      ratio and in the size of the eggs. Acuaria irhami sp. nov. is described based on
      two male specimens from under the gizzard lining of Dicrurus hottentottus
      jentincki. The new species can be distinguished easily from all congeners except
      from A. microecae, in having equal rather than subequal or dissimilar spicules.
      However, the new species can be differentiated from A. microecae in the number of
      postanal papillae, in the median preanal papilla and in the length of the
      cordons.

PMID- 19840431
TI  - Efficacy of laser occlusion of posterior semicircular canal for benign paroxysmal
      positional vertigo: case report.
AB  - OBJECTIVE: To observe the long-term effect of laser occlusion of the posterior
      semicircular canal for benign paroxysmal positional vertigo. METHOD: Case report
      and review of the relevant world literature. RESULTS: We treated a patient with
      refractory benign paroxysmal positional vertigo using laser occlusion of the
      posterior semicircular canal, and achieved satisfactory results. Three months
      after the operation, the patient was able to lead a normal life. There was no
      recurrence over five years of follow up. CONCLUSION: To our knowledge, this is
      the first report in the world literature of a patient with refractory benign
      paroxysmal positional vertigo being treated with laser occlusion of the posterior
      semicircular canal. This method had long-term effectiveness, and may be one of
      the most effective methods of treating patients with refractory benign paroxysmal
      positional vertigo.

PMID- 19840432
TI  - Acoustically evoked, short latency negative response in children with
      sensorineural hearing loss.
AB  - INTRODUCTION: The auditory brainstem response consists of fast and slow waves.
      The acoustically evoked, short latency negative response is a large, negative
      deflection with a latency of 3 milliseconds which has been reported in patients
      with profound hearing loss. It may be of vestibular, particularly saccular,
      origin, as is the vestibular evoked myogenic potential. PURPOSE: To assess the
      presence of acoustically evoked, short latency negative responses in children
      with severe to profound sensorineural hearing loss. MATERIALS AND METHODS: Twenty
      three children (46 ears) with sensorineural hearing loss underwent audiological
      evaluation and auditory brainstem response, vestibular evoked myogenic potential
      and caloric testing. RESULTS: An acoustically evoked, short latency negative
      response was present in 30.43 per cent of ears and absent in 69.57 per cent.
      Vestibular evoked myogenic potentials were recorded in all ears in the former
      group, but in only 53.13 per cent in the latter group. Caloric testing was normal
      in 82.6 per cent of the total ears tested. CONCLUSION: The presence of an
      acoustically evoked, short latency negative response is dependent not on residual
      hearing but on normal saccular function. This response can be measured in
      patients who cannot contract their neck muscles.

PMID- 19840433
TI  - Multinodular goitre in lingual thyroid: case report.
AB  - OBJECTIVE: We report a case of a multinodular goitre developing in a lingual
      thyroid. METHOD: Case report, and discussion of the embryology and treatment of
      lingual thyroids. CASE REPORT: A 66-year-old woman presented with dysphagia
      secondary to a multinodular lingual goitre. A previously silent lingual thyroid
      had undergone multinodular change to cause dysphagia and eventually airway
      compromise. The goitre was excised via a midline, mandible-splitting approach.
      CONCLUSION: Lingual thyroids have an incidence of one in 3,000 to 10,000. There
      has not previously been a reported case of such an ectopic gland undergoing
      multinodular changes and presenting in later life.

PMID- 19840434
TI  - [Reprogramming in origin and development of leukemia stem/progenitor cells].
AB  - The success of yielding induced pluripotent stem (iPS) cells from human somatic
      cells demonstrates the important role of reprogramming in the formation of
      stem/progenitor cells and initiates the exploration of the origin of leukemia
      stem cells. In our previous work, we have found two types of leukemia, bona fide
      leukemia and non-bona fide leukemia. Different leukemias originate from different
      leukemia stem/progenitor cells which are critical to the genesis and evolution of
      leukemia. Bona fide leukemia and non-bona fide leukemia originate from leukemia
      stem cells and progenitor cells, respectively. Recent research suggests that
      different types of leukemia are influenced by the reprogramming state of their
      origin cells.

PMID- 19840435
TI  - [Structural feature and biological function of PPP2R5C gene].
AB  - PPP2R5C is one of the members of regulatory subunits of protein phosphatase 2A
      (PP2A), which plays a critical role in cell proliferation, differentiation and
      transformation, based on its induction of dephosphorylation of P53 at various
      residues. Recently, it was characterized that the alteration of expression
      pattern of PPP2R5C is associated with cell malignant transformation, thus PPP2R5C
      was thought as a marker for progressive disease in B-CLL. In this article the
      gene structure and biological function of PPP2R5C as well as relation of PPP2R5C
      with genesis and development of cancer were discussed.

PMID- 19840436
TI  - [Interaction between mixed-lineage leukemia and Menin proteins].
AB  - The study was aimed to investigate the subcellular localization of mixed-lineage
      leukemia (MLL) and Menin proteins, and to explore the interaction between these
      two proteins. The recombinant eukaryotic cell expression vectors of pcDNA3.1-myc
      MLL and pCMV-flag-Menin were constructed respectively, and transfected into the
      HEK293T cells. Immunofluorescence technique was used to observe the subcellular
      localization of the two proteins. Co-immunoprecipitation and Western blot methods
      were applied to evaluate the expression and interaction of the two proteins. The
      results showed that MLL and Menin proteins could be co-localized in cell nuclei,
      and the study of binding in vivo revealed that MLL protein could be detected in
      the immunoprecipitation complex of anti-FLAG, while Menin proteins could also be
      found in the immunoprecipitation complex of anti-MYC. It is concluded that MLL
      and Menin proteins co-localized in cell nuclei have same location and the
      interaction exists between MLL and Menin proteins.

PMID- 19840437
TI  - [FMS-like tyrosine kinase 3 gene mutations in acute myeloid leukemia].
AB  - This study was aimed to investigate the frequency of FMS-like tyrosine kinase 3
      (FLT3) mutations including internal tandem duplication (ITD) mutation of
      juxtamembrane region and point mutation of the second tyrosine kinase domain
      (TKD) in acute myeloid leukemia (AML) patients and its clinical significance. The
      ITD mutation in FLT3 exon 14, 15 of bone marrow mononuclear cells was detected by
      genomic DNA-PCR, the TKD point mutation in FLT3 exon 20 was detected by genomic
      DNA-PCR combined with restriction endonuclease digest. The results indicated that
      among 131 newly diagnosed AML patients, 21 patients (16.0%) showed FLT3-ITD
      positive, 3 patients (2.3%) showed FLT3-TKD positive. None was found harboring
      both mutations. The WBC and bone marrow blast counts in FLT3-ITD positive
      patients seemed both higher than those in patients with wild-type FLT3 (FLT3-wt),
      but there was significant difference only in WBC count (p<0.05). The complete
      remission (CR) rate in FLT3-ITD positive patients was 47.6%, which was
      significantly lower than that in FLT3-wt patients (88.1%, p<0.05). There was no
      statistical difference in CR rate between FLT3-ITD positive and negative patients
      in 20 cases of M3; the CR rate in FLT3-ITD positive patients with non M(3) was
      37.5 (6/16) which was obviously lower than that in FLT3-wt patients with non M3
      (90.6%, 48/53) (p<0.05). 3 FLT3-ITD positive patients with CR relapsed after CR
      for 14 (2-20) months with relapse rate 50% (3/6) which was higher than that in
      FLT3-wt patients (29.2%, 14/48). It is concluded that FLT3 mutation is common in
      AML patients, while FLT3-ITD mutation is more frequent than FLT3-TKD mutation.
      The AML patients with FLT3-ITD mutation have a poor prognosis, while FLT3-TKD
      point mutation does not significantly influences prognosis of the patients.
      Therefore early detection of FLT3 mutation may be important for targeting therapy
      and evaluating clinical prognosis of AML patients.

PMID- 19840438
TI  - [Preliminary study on leukemia related gene zo-1 involved in pathogenesis of
      leukemia].
AB  - The study was aimed to identify a new leukemia related gene zo-1 from leukemia
      and to explore its mechanism in leukemia. Methylation specific PCR (MSP) was used
      for testing gene zo-1 methylation in leukemia cells. The gene zo-1 specific siRNA
      was designed according to its sequence, and transfected into THP-1 cell, and the
      cells were cultured for 48 hours before harvesting. The effect of zo-1 siRNA was
      monitored by RT-PCR. The cellular proliferation activity was assayed by CCK-8,
      the apoptosis was detected by Annexin-V-fluorescence in isothiocyanate (FITC)
      assay, and cell cycle was observed by propidium iodide (PI). The results
      indicated that the gene zo-1 in patients with acute leukemia was hypermethylated,
      while the gene zo-1 in healthy persons was unmethylated. The THP-1 cells with
      unmethylation of zo-1 gene promoter overexpressed the gene zo-1, while the Molt4
      and HL-60 cells with hypermethylation of gene zo-1 promoter did not express the
      gene zo-1. The silenced zo-1 gene in Molt4 and HL-60 leukemia cell lines could be
      reactivated by demethylation treatment with 5-AZA-dC. The oligofectamine
      transfected siRNA for zo-1 gene successfully inhibited the expression of gene zo
      1 in THP-1 cells, but did not interfere with cell proliferation, cell cycle and
      apoptosis. It is concluded that gene zo-1 is a leukemia-related gene. Gene zo-1
      in acute leukemia was hypermethylated, the methylation status of gene zo-1
      regulates the expression of gene zo-1. Lack of gene zo-1 expression in THP-1
      cells does not influence the cell proliferation, apoptosis and cell cycle, which
      suggests that the methylation of gene zo-1 may be involved in the genesis of
      acute leukemia, its mechanism is worthy to be studied.

PMID- 19840439
TI  - [FLT3-ITD detection of free DNA in plasma from 235 patients with acute myeloid
      leukemia and its clinical significance].
AB  - This study was purposed to evaluate the clinical significance of FLT3-ITD of free
      DNA in plasma from patients with AML. Free DNA in plasma of 235 patients with AML
      were extracted and identified by globin gene. FLT3 was amplified by PCR and
      compared with detected results of leukemic cellular DNA (BM or PB). The results
      indicated that out of total 235 patients, globin gene in plasma free DNA was
      successfully amplified from 190 cases. In 188 newly diagnosed, replaced and
      refractory cases, 35 cases showed ITD mutation (19%). And they also showed ITD
      mutation in leukemic cellular DNA. But in 47 patients in remission, 2 patients
      with FLT3-ITD mutation of free DNA in plasma had no mutation in cellular DNA, but
      got relapse early. Compared with patients of FLT3-wt, patients with FLT3-ITD
      mutation had increased WBC count and expression rate of CD7, CD56 and decreased
      CR rate. It is concluded that leukemic-specific DNA in plasma can be detected in
      AML patients and consistent with detected results of leukemic cellular DNA.
      Furthermore, the free DNA in plasma is more sensitive for MRD monitoring in
      remitted patients. FLT3-ITD detection plays an important role in evaluation of
      prognosis and molecular target therapy for AML patients.

PMID- 19840440
TI  - [Correlation of human resistin gene expression with leukemia incidence].
AB  - Although the effect of mouse resistin on insulin-resistance has been well
      defined, but the biological function of human resistin is still unknown. This
      study was aimed to explore the possible physiological and pathological effects of
      human resistin, as well as the tissue distribution of human resistin and
      correlation of resistin gene expression with leukemia incidence. 152 leukemia
      patients without inflammatory complication and 100 healthy persons were selected
      as experimental and control groups respectively. The blood samples were
      collected, the total RNA was extracted, the expression distribution of resistin
      in different tissues was detected by semi-quantitative RT-PCR and then the
      statistical analysis was carried out. The results indicated that the expression
      of the human resistin gene was detected in normal fetus liver, adult bone marrow
      and umbilical cord blood and peripheral blood cells, while the resistin gene
      could not be amplified in fat, umbilical cord, placenta and adult liver. The
      resistin expression was detected in 21% leukemia patients and 27% healthy
      persons. The difference of the resistin gene expression between the two groups
      was not statistically significant (p>0.05). It is concluded that the higher
      expression of resistin exists in normal human fetus liver, adult bone marrow,
      umbilical cord blood and peripheral blood cells, which indicates that the
      distribution of human resistin correlates with normal hematopoiesis in certain
      extent, but its expression level and rate may not correlate with the incidence of
      leukemia.

PMID- 19840441
TI  - [Promotive effect of LRP16 gene on proliferation of K562 cells].
AB  - The study was aimed to investigate the promotive effect of LRP16 gene on K562
      cell proliferation. Open reading frame of LRP16 gene was amplified using reverse
      transcription-polymerase chain reaction (RT-PCR) and ligated to pGEM-T plasmid to
      construct LRP16 ORF-pGEM-T recombinant vector. Then, LRP16 ORF identified by
      sequencing was inserted into pcDNA3.1+ plasmid to construct LRP16 ORF-pcDNA3.1+
      recombinant expression plasmid which was transfected into K562 cell lines to make
      overexpression of LRP16 gene in K562 cells. Survival of cells was determined by
      MTT assay and growth curve of cells was drawn, the cell cycle was detected by
      flow cytometry. The results showed that LRP16 ORF was successfully amplified,
      then the LRP16 ORF-pcDNA3.1+ recombinant plasmid was constructed. The K562 cell
      line with overexpression of LRP16 gene was established. The promotive effect of
      LRP16 gene overexpression on proliferation of K562 cells was observed and the
      effect partially related to the enhancement of cells from G0 to S phase induced
      by LRP16 gene. It is concluded that LRP16 gene overexpression shows a promotive
      effect on proliferation of K562 cells.

PMID- 19840442
TI  - [Abnormality of serum immunoglobulin in peripheral blood of patients with chronic
      lymphocytic leukemia].
AB  - In order to investigate the relation of serum immunoglobulin (Ig) level to age,
      sex, disease stages and prognosis in chronic lymphocytic leukemia (CLL) patients,
      the levels of serum IgG, IgA and IgM in 83 CLL patients were detected by immune
      rate turbidimetry. the expressions of CD38 and ZAP-70 in CLL cells were
      determined by multi-parameter flow cytometry (FCM). The results showed that among
      the 83 CLL patients, the IgG, IgA and IgM levels were reduced in 12 (14.5%), 26
      (31.3%) and 34 cases (41.0%) respectively. The incidence of Ig reduction was
      higher in Binet C stage than that in Binet A and B (p=0.011). There was higher
      incidence of Ig reduction in high-risk group of Rai stage than that in low-risk
      group (p=0.011). The positive rate of CD38 or ZAP-70 was significantly higher in
      Ig reduction group than that in normal Ig level group (p=0.033 and p=0.038
      respectively). The positive rate of CD38 and ZAP-70 was also higer in advanced
      disease, and among them the positive rate of ZAP-70 expression in Binet C stage
      was obviously higer than Binet A and B (p=0.047). Nonetheless, there was no
      significant relationship of Ig level with gender and age (p>0.05). It is
      concluded that the function of humoral immunity in CLL patient is closely related
      to the disease stages. The serum Ig detection seems important for evaluating
      immunologic state and prognosis of CLL patients.

PMID- 19840443
TI  - [Analysis of cells in Tel/aml-1 positive childhood acute lymphoblastic leukemia
      by two-dimensional gel electrophoresis].
AB  - This study was aimed to establish the protein expression profile of tel/aml-1+
      childhood acute lymphoblastic leukemia (ALL) with different prognoses by two
      dimensional polyacrylamide gel electrophoresis and explore the nosogenesis of
      tel/aml-1+ ALL childhood. On the basis of leukocyte count at new diagnosis, early
      reaction to therapy and clinical prognosis, the patients with tel/aml-1+ ALL were
      divided into 3 groups: early relapse group, high leukocyte count group and
      standard risk group. The bone marrow was taken from newly diagnosed patients for
      isolating protein, then the protein in leukemia cells was isolated by two
      dimensional polyacrylamide gel electrophoresis, the image analysis of
      differential protein among 3 groups was carried out by using the PDQuest 7.3.0
      image analysis software. The results showed that there were significant
      difference of protein expression profile among 3 groups. As compared with high
      leukocyte count and standard risk groups, 71 protein spots disappeared, 93 new
      protein spots appeared, the expression of 37 protein spots was up-regulated and
      the expression of 23 protein spots was down-regulated in early relapse group. As
      compared with high leukocyte count group, 6 protein spots disappeared, 56 new
      protein spots appeared, the expression of 7 protein spots was up-regulated, and
      expression of 19 protein spots was down-regulated in standard risk group. It is
      concluded that the protein expression profile in early relapse group is
      significantly different from other groups. Some proteins may play an important
      role in pathogenesis of childhood tel/aml-1+ ALL, and probably become new
      molecular indicators and targets for individualized treatment.

PMID- 19840444
TI  - [Expression of genes psma6 and slc25a4 in patients with acute monocytic
      leukemia].
AB  - The aim of this study was to investigate the expression levels of genes psma6 and
      slc25a4 in bone marrow of patients with acute monocytic leukemia and their
      correlation with clinical features and prognosis. The expression levels of genes
      psma6 and slc25a4 in AML-M5 leukemia cells, normal blood cells and non-leukemia
      cells were detected by real-time quantitative RT-PCR and compared each other. The
      expression levels of psma6-encoding protein P27K was assayed by using
      immunohistochemistry method. The results showed that the expression levels of
      psma6 mRNA in AML-M5 leukemia cells was lower than that in non AML-M5 leukemia
      cells, non-leukemia cells and normal blood cells. The results obtained by
      immunohistochemistry assay were consistent with above-mentioned results. The
      expression level of psma6 in AML-M5 patients with complete remission was higher
      than that in AML-M5 patients without remission. The expression level of P27K
      protein in AML-M5 and AL correlated to leukocyte count in peripheral blood and
      LDH content. The overexpression of slc25a4 mRNA was found in AML-M5, but there
      was no significant difference in slc25a4 mRNA expression between the patients
      with complete remission and those without remission. It is concluded that the
      expression level of psma6 is probably a new prognostic indicator of acute
      monocytic leukemia, slc25a4 may be a novel gene of antigen associated with acute
      monocytic leukemia.

PMID- 19840445
TI  - [Immunophenotypes, cytogenetics and clinical features of 192 patients with acute
      myeloid leukemia].
AB  - The objective of this study was to investigate the immunophenotypic subtype
      profiles of 192 patients with acute myeloid leukemia (AML) and its association to
      cytogenetics and clinical features. Immunophenotyping of 192 patients was
      performed by flow cytometry using a panel of monoclonal antibodies. The
      karyotypes in 125 out of 192 cases were analyzed by G-banding technology. The
      results showed that CD33, CD13, myeloperoxidase (MPO) and CD117 were the most
      commonly expressed antigens in AML. CD117 expressed in 84.6% of AML-M3 cases. A
      combination of intensive autofluorescence, both CD34- and HLA-DR-, and high
      expression of CD13, CD33 and MPO had significant value for AML-M3 diagnosis. CD14
      expressed only in AML-M4 and AML-M5, and both intensive positivity of CD64 and
      CD15 with high expression of HLA-DR may suggest great possibility for diagnosis
      of AML-M5. Lymphoid marker expression was documented in 47.9% of the 192 AML
      cases. CD56 (26.0%) and CD7 (20.8%) were the most commonly expressed lymphoid
      markers in AML patients, followed by CD19 (9.9%) and CD2 (7.3%). Abnormal
      karyotypes were detected in 76 out of 125 cases (60.8%). Correlation test showed
      that t(8;21) was found only in 17 cases of AML-M2 and strongly associated with
      the individual or combinational expressions of CD15/CD19/CD56. And 28 cases of
      t(15;17) were found in AML-M3; 2 cases of inv(16) were found in AML-M4EO. Higher
      CD34 positivity was found in LymAg+ group (77.2%) than that in LymAg- group
      (48.0%). It is concluded that immunophenotype analysis is useful for AML
      diagnosis and classification, and the immunophenotype has close relevance to the
      abnormal cytogenetic changes and clinical features in AML. The results suggested
      that a new prognostic scoring system that integrated the morphology, cytogenetic
      abnormalities and immunophenotype parameters would benefit the diagnosis,
      classification, and estimation of prognosis in AML patients.

PMID- 19840446
TI  - [Effect of tetrandrine combined with daunorubicin on expressions of P21 and P-gp
      in K562/A02 cells].
AB  - This study was aimed to investigate the reversal effect of Tetrandrine (TET)
      combined with daunorubicin (DNR) on multidrug resistance (MDR) of K562/A02 cells
      and its relation to P21, P-gp and their genes so as to provide the new theoretic
      evidence for clinical use of TET. The experiments were divided into 4 groups:
      control group (DNR alone), combined 1 group (DNA+0.5 mg/L TET), combined 2 group
      (DNR+1.0 mg/L TET) and combined 3 group (DNR+2.0 mg/L TET). The expressions of
      P21, P-gp and mdr-1 gene in K562/A02 cells of different groups were detected by
      Western blot, flow cytometry and semi-quantitative PCR respectively. The results
      showed that the expression of P21 was enhanced along with increasing of TET
      concentration, the expression of P-gp was reduced along with increasing of TET
      concentration and expression of mdr-1 gene was almost not observed in K562 cells,
      but the high expression of mdr-1 gene was seen in K562/A02 cells, furthermore,
      the expression of mdr-1 gene in K562/A02 cells increasingly was reduced along
      with increasing of TET concentration. It is concluded that the TET possesses the
      reversal effect on multiple drug resistance of K562/A02 cells with concentration
      dependence, the reversal effect of TET may be related to up-regulation of P21
      expression and down-regulation of P-gp and mdr-1 gene expressions in K562/A02
      cells.

PMID- 19840447
TI  - MDR reversal activity of bromotetrandrine in vitro and in vivo.
AB  - The present study was aimed to evaluate the MDR reversal activity of
      bromotetrandrine (BrTet) in vitro and in vivo. The inhibitory effects of
      adriamycin (ADM) used alone or in combination with BrTet or Tet on the
      proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The ADM
      accumulation and the protein levels of P-glycoprotein (P-gp) were detected by
      flow cytometry. The mRNA levels of P-gp were determined by RT-PCR. The in vivo
      effect of BrTet and Tet was investigated by using nude mice grafted with
      sensitive human leukemia cell line K562 and MDR cell line K562/A02. The results
      showed that BrTet at 0.25, 0.5 and 1 micromol/L reversed the resistance to ADM in
      MDR K562/A02 cells in a dose-dependent manner. Flow cytometry suggested that
      BrTet significantly increased the intracellular accumulation of ADM in K562/A02
      cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp
      in K562/A02 cells, and down-regulated mdr1 expression. In nude mice bearing K562
      xenografts on the left flank and K562/A02 xenografts on the right flank,
      intraperitoneal injection of 10 mg/kg BrTet significantly enhanced the antitumor
      activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while
      ADM alone inhibited the growth of K562/A02 xenografts only by 5.8%. No
      enhancement effect by BrTet was seen in K562 xenografts. It is concluded that
      BrTet shows significant MDR reversal activity in vitro and in vivo. Its activity
      may be related to the inhibition of P-gp overexpression and the increase
      intracellular accumulation of anticancer drugs. BrTet may be a promising-MDR
      modulator for eventual assessment in the clinic.

PMID- 19840448
TI  - [Calcium ionophore induces the differentiation of chronic myeloid leukemia cells
      into dendritic cells].
AB  - The aim of this study was to investigate the ability of calcium ionophore (CI )
      to induce the differentiation of CML cells into dendritic cells (DC), to analyze
      the P210 expression in DCs and to evaluate the stimulatory effect of CML-DC on
      production of cytotoxic activity against CML cells via activating the autologous
      T cells. The mononuclear cells were isolated from bone marrow of CML patients
      whose WBC counts were more than 30x10(9)/L when samples were collected, then the
      lymphocytes and monocytes were discarded by pouring out supernatant twice at
      different culture time point. Slightly adherent cells were cultured in RPMI 1640
      containing 10% FCS, with or without CI (375 ng/ml) and GM-CSF (200 ng/ml) at 37
      degrees C, 5% CO2, fully humidified atmosphere for 96 hours. The cell morphology
      was observed under the inverted microscope and electron microscope; the
      expression of CD antigens was analyzed with flow cytometry; the P210 expression
      was measured with Western blot. LDH assay was used to evaluate the effect of
      cultured CML cells (CML-DC) generating cytotoxic T lymphocyte (CTL) activity
      against CML cells. The results indicated that after treatment with calcium
      ionophore and GM-CSF for 96 hours, CML cells showed DC morphological
      characteristics under inverted microscope and electron microscope. The expression
      of CD83, CD86, CD40, CD80 and HLA-DR increased remarkably. P210 was expressed in
      the CML-DC, but the expression level was lower than that in CML cells without CI
      and GM-CSF treatment. LDH assay showed that the CTL activity against CML was
      found greater in autologous T cells activated by CML-DC than that by CML cells.
      It is concluded that the CML cells can be induced to quickly differentiate into
      DC when cultured with CI and GM-CSF. CML-DC expresses P210, but the expression
      level is lower than that in CML cells. CML-DC can stimulate autologous T cells to
      produce CTL against CML.

PMID- 19840449
TI  - [Effects of baicalin on proliferation and apoptosis of adriamycin-resistant human
      leukemia HL-60/ADR cells].
AB  - This study was purposed to explore the effects of baicalin on proliferation and
      apoptosis of adriamycin-resistant human myeloid leukemia cell line HL-60/ADR. HL
      60/ADR cells were in vitro cultured and its proliferation inhibition was detected
      by MTT assay. The cell apoptosis was tested by Annexin V FITC/PI double staining
      analysis, DNA fragmentation and TUNEL labeling method. The expressions of c-myc
      and bcl-2 mRNA were detected by RT-PCR, and the protein expressions of C-MYC, BCL
      2, caspase-3 precursor (procaspase-3), PARP and BAD were determined by Western
      blot. The results showed that baicalin could remarkably inhibited the HL-60/ADR
      cell proliferation, the cell doubling time was 48 hours, with an IC50 value of 28
      micromol/L. Apoptosis occurred in dose dependent manner (20, 40, 80 micromol/L),
      and cell apoptosis in earlier and later stages could be detected by Annexin V
      FITC/PI double staining analysis, DNA fragmentation and TUNEL labeling method.
      The expressions of c-myc and bcl-2 mRNA in baicalin-treated cells decreased in a
      time-dependent manner (12, 24, 48 hours). Meanwhile, protein expressions of C
      MYC, BBL-2, procaspase-3 and PARP (116 kD) were down-regulated in a time
      dependent manner, while the expression of PARP (85 kD) and BAD were up-regulated.
      It is concluded that the baicalin efficiently induces proliferative inhibition
      and apoptosis in HL-60/ADR cells. All of above related genes and proteins may be
      involved in these processes.

PMID- 19840450
TI  - [Effect of emodin on induction of apoptosis in jurkat cells and its possible
      mechanisms].
AB  - The aim of study was to investigate the effect of a traditional Chinese medicine,
      emodin, on proliferation and apoptosis in T lymphocytic leukemic cell line Jurkat
      and its mechanisms. Cell proliferation inhibition was detected by MTT assay. Cell
      apoptosis was measured by DNA ladder and terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL) assay. The expressions of related
      proteins and caspase family members were determined by Western blot. The results
      showed that emodin inhibited proliferation in Jurkat cells, with an IC50 about 20
      micromol/L and induced cell apoptosis in both time-and dose-dependent manners.
      The expressions of proliferation-related protein C-MYC, hTERT and apoptosis
      related protein BCL-2 were down-regulated in a time dependent manner after the
      treatment with emodin. The expressions of procaspase-3, -8 and -9 all decreased
      while activated caspase-3 and PARP expressions were up-regulated. It is concluded
      that emodin can remarkably inhibit cell proliferation and induce apoptosis in
      Jurkat cells. The down-regulation of proliferation-related proteins C-MYC, hTERT
      and apoptosis-related protein BCL-2 expressions and activation of caspase cascade
      may be involved in the process of apoptosis.

PMID- 19840451
TI  - [Changes and mechanism of apoptosis-related gene expression in T lymphocytic
      leukemia JM cells induced with matrine].
AB  - This study was purposed to investigate the changes of apoptosis-related gene
      expression in T lymphocytic leukemia JM cells induced with matrine, and its
      possible mechanism. JM cells was induced with 0.4 mg/ml matrine for 4 days, the
      total RNA was extracted from JM cells before and after matrine induction, the
      differential expression of apoptosis-related genes were screened with cDNA
      Expression Array Kit, the expression change of a part of gene was checked by
      Western blot. The results indicated that after induction of JM cells with
      matrine, differential expression of 31 genes were found by gene chip
      hybridization, the expression of caspase 8 was up-regulated more than 5 times.
      Western blot analysis showed that the up-regulation of caspase 8 gene expression
      positively correlated with induction time. It is concluded that differential
      expressions of many apoptosis-related genes in JM cells can be induced by
      matrine, in which gene expression of caspase 8 is up-regulated notably.

PMID- 19840452
TI  - [Antileukemic effects in vitro of new co-stimulatory molecule CD137].
AB  - This study was aimed to investigate the expression characteristics of new co
      stimulatory molecule CD137 (4-1BB) on human T lymphocytes and antileukemic
      effects of monoclonal antibody hCD137mAb in stimulating the T lymphocyte
      proliferation, promoting the cytokine secretion, enhancing the cell killing
      effect and so on. The expression of CD137 on normal T lymphocytes treated with
      phytohemagglutinin (PHA) was detected by FACS and indirect immunofluorescence. In
      HL-60 and T lymphocyte system in vitro, the effect of hCD137mAb and PHA on T
      lymphocyte proliferation was tested by MTT colorimetric assay. The IFN-gamma and
      IL-4 expression levels on the surface of T cells were detected by FACS and
      indirect immunofluorescence. In vitro mixed lymphocyte tumor cell culture (MLTC)
      system, the function of hCD137mAb enhancing toxicity killing leukemic cells at
      different effect-target ratio were studied. The results showed that almost no
      expression of hCD137 was found in T cells without PHA stimulation, but after
      activation of T cells by PHA, the expression gradually increased with a peak at
      7th day (FACS 56.4%+/-1.98%, indirect immunofluorescence 52.8%+/-2.01%). CD137mAb
      alone could not stimulate T cell proliferation (proliferation index 1.002+/
      0.011), but could enhance PHA stimulating activity (proliferative index of
      2.161+/-0.102) about 2-folds (proliferation index 4.705+/-0.133). Moreover,
      hCD137mAb increased expression of IFN-gamma high by about 3-fold in presence of
      PHA, but did not effect on IL-4. The hCD137mAb markedly enhanced T cell killing
      activity on HL-60 cell line and its co-stimulatory effect was best at the effect
      target ratio of 40:1 with increasing of killing percentage by about 2-fold. It is
      concluded that the new co-stimulatory molecule CD137 has significant antileukemic
      effect, use of hCD137mAb is an effective, safe and simple immunization strategy
      for leukemia therapy, this study provides some experimental basis for clinical
      immunotherapy with CD137 mAb.

PMID- 19840453
TI  - [Synergistic effects of proteasome inhibitor and histone deacetylase inhibitor on
      apoptosis and aggresome formation in T lymphoma cells].
AB  - The aim of the study was to explore the synergistic effect of the proteasome
      inhibitor bortezomib (bor) and the histone deacetylase inhibitor suberoylanilide
      hydroxamic acid (SAHA) on apoptosis of T lymphoma cell lines Jurkat and Hut78,
      and on the formation of aggresome. Jurkat and Hut78 cells were treated with bor
      (10 nmol/L) or bor (10 nmol/L) combined with SAHA (2 micromol/L) respectively.
      Cell growth inhibition was estimated by trypan blue dye exclusion test. Cell
      morphology was evaluated by light microscopy with Wright's staining of
      cytocentrifuge preparations. Cell apoptosis was analyzed by flow cytometry.
      Ultrastructure of cell apoptosis and aggresome were observed by transmission
      electron microscopy. The results showed that proliferation of both Jurkat and
      Hut78 cells was significantly inhibited in the bor+SAHA group, as compared with
      the control group and the bor alone group. Flow cytometric analysis confirmed
      that the percentage of apoptosis in Jurkat and Hut78 cells in the bor+SAHA group
      (41.8+/-4.7% and 72.7+/-11.7% respectively) was remarkably higher than those in
      the control group (3.6+/-1.3% and 7.0+/-1.9% respectively) and the bor alone
      group (6.3+/-2.3% and 18.7+/-9.2% respectively) (p<0.01). Ultrastructure
      examination revealed that typical aggresomes in cells could be observed in bor
      alone group. The combination of bor and SAHA diminished both the amount and
      density of aggresomes, or even eliminated them, accompanied by the increased rate
      of apoptosis. It is concluded that proteasome inhibitor combined with histone
      deacetylase inhibitor synergically induces T lymphoma cell apoptosis. Bortezomib
      stimulates the formation of aggresome, while SAHA destroys this aggresome
      structure, which may be one of the mechanisms underlying the enhancement of
      bortezomib-induced apoptosis.

PMID- 19840454
TI  - [Establishment of an animal model with thymic lymphoma in mice].
AB  - The objective of study was to establish an animal model with thymic lymphoma in
      mice induced by intraperitoneal injection of DNA alkylating agent N-methyl-N
      nitrosourea (MNU). Male and female mice of the C57BL/6 strain were injected by
      the intraperitoneal route with MNU solution in a dosage of 50 mg/kg body weight.
      The injection was repeated at week 8. Following injection of MNU, the general
      status of mice was observed. All mice were sacrificed for autopsy at the 22nd
      experimental week. Complete gross examination was performed for detection of
      tumor masses. The results showed that at the 22nd week, the incidence of thymic
      lymphoma in MNU-treated animals was 67.5% (27/40). No significant sex difference
      in the incidence of thymic lymphoma was observed. In conclusions, an animal model
      with thymic lymphoma in mice can be established by twice intraperitoneal
      administration of MNU. The biological behavior of the induced tumors resembles to
      those of human thymic lymphoma derived from thymic T-cells.

PMID- 19840455
TI  - [Effect of betulinic acid on inducing apoptosis of human multiple myeloma cell
      line RPMI-8226].
AB  - The aim of this study was to investigate the effect of betulinic acid on inducing
      apoptosis of human multiple myeloma RPMI-8226 cell line. The inhibitory effect of
      betulinic acid on proliferation and its inducing apoptosis effect, influence on
      cell cycle and induced morphological changes of RPMI-8226 were evaluated by MTT,
      flow cytometry Annexin-V/PI double staining, flow cytometry with PI staining and
      fluorescence microscopy with Hoechst33258 staining, respectively. The
      transcription level changes of bcl-xl gene and caspase 3 which are two kinds of
      apoptosis related protein gene were determined by RT-PCR. The results showed that
      within a certain range of concentration (0, 5, 10, 15, 20 microg/ml), IC50 of
      betulinic acid to RPMI-8226 at 24 hours was 10.156+/-0.659 microg/ml, while the
      IC50 at 48 hours was 5.434+/-0.212 microg/ml, and its inhibiting effect on
      proliferation of RPMI-8226 showed both time-and dose-dependent manners. Flow
      cytometry with Annexin-V/PI double staining revealed that apoptotic rate of RPMI
      8226 cells increased as betulinic acid concentration increased. Flow cytometry
      with PI staining showed that the ratio of cells in G0/G1 phase increased, while
      it in S phase decreased, and ratio of cells at G2/M phase did not present a
      significant change. Morphological differences were typical and obvious between
      cells in treated and control groups under fluorescence microscope using
      Hoechst33258 staining. RT-PCR detection of caspase 3 gene indicated that its
      transcription level showed an increasing trend as the concentration of betulinic
      acid increased, while the bcl-xl showed the opposite trend. It is concluded that
      the betulinic acid can induce apoptosis of RPMI-8226 within a certain range of
      concentration in a time- and dose-dependent manners. This phenomenon may be
      related to the transcriptional level increase of caspase 3 gene and decrease of
      bcl-xl. Betulinic acid also affects G1/S in cell cycle which arrests cells at
      phase G0/G1.

PMID- 19840456
TI  - [Fluorescence in situ hybridization on bone marrow smear in the detection of
      cytogenetic aberrations of multiple myeloma].
AB  - This study was aimed to establish the technique of interphase fluorescence in
      situ hybridization (I-FISH) used on smear of bone marrow directly, and to develop
      a new method for detection of the molecular cytogenetics in multiple myeloma
      (MM). After a series of treatment, fixation and digestion of the bone marrow
      smear as the carrier, the chromosome 8 centromere probe were used in I-FISH for
      molecular cytogenetics detection. At the same time, differences were compared in
      the results between the new method and the conventional I-FISH. The results
      showed that there was no statistically significant difference of proportion of
      various signals in non-hematologic malignancies when detected with the two
      methods (p>0.05). In bone marrow smear I-FISH, 8 out of 19 cases (42.1%) had
      abnormality of chromosome 8, including 5 cases with -8 (26.3%) and 3 cases with
      +8 (15.8%). It is concluded that the I-FISH on smear of bone marrow is
      characterized by convenience, economy and accuracy. Therefore, it can be used for
      research of molecular cytogenetics in MM.

PMID- 19840457
TI  - [Detection of single nucleotide polymorphisms of Jak2 gene in multiple myeloma by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry].
AB  - This study was purposed to investigate the practicality of matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for
      detection of single nucleotide polymorphisms (SNP) on jak2 gene in multiple
      myeloma (MM) cells. The DNA fragment containing 2 SNPs of jak2 (C428T and C643T)
      was amplified using PCR and was purified. The purified product was used as the
      template for primer extension (PEX). The small products of allele-specific
      reaction were purified, the SNPs on jak2 gene of 5 patients with MM and 5 healthy
      persons were detected by MALDI-TOF MS. The results showed that the distribution
      of genotype C428T and C643T was not different between MM patients and healthy
      persons, both of which are homozygous T/T. In conclusion, the method based on
      MALDI-TOF MS and PEX technique for detecting SNP in jak2 gene is rapid, accurate
      and reliable method, and can be used in clinical practice.

PMID- 19840458
TI  - [Expression of pituitary tumor transforming gene and C-myc gene in patients with
      multiple myeloma].
AB  - The study was purposed to explore the expressions of pituitary tumor transforming
      gene and c-myc gene in patients with multiple myeloma (MM) and its relationship
      with pathogenesis of MM. Expressions of pituitary tumor transforming gene and c
      myc gene mRNA in BMMNC from 33 patients with MM and 10 normal controls were
      detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The results
      showed that the expressions of pituitary tumor transforming gene and c-myc gene
      mRNA were significantly higher in MM patients those that in normal controls
      (p<0.05). The expression of pituitary tumor transforming gene mRNA was
      significantly correlated with the expression of c-myc gene (r=0.801, p<0.05). In
      conclusion, the overexpressions of pituitary tumor transforming gene and c-myc
      gene may be related to the pathogenesis and progression of MM.

PMID- 19840459
TI  - [Mechanism of C-reactive protein on proliferation of multiple myeloma U266
      cells].
AB  - This study was purposed to investigate the mechanism of C-reactive protein (CRP)
      on proliferation of U266 cells. The human multiple myeloma cell line U266 was
      incubated with human CRP (0, 5, 10, 20 mg/L) for 24 hours, then the proliferation
      level of U266 cells was detected by using blood analyser. The mRNA expressions of
      survivin and HSP90alpha were examined by RT-PCR. The results showed that the
      proliferation ratio was increased, as compared with the control group (p<0.05);
      furthermore, the mRNA levels of survivin and HSP90alpha were up-regulated in
      proportion to the increased CRP concentrations. There was significant correlation
      between expression of survivin and HSP90alpha (r=0.737, p<0.0001) in incubated
      cells. It is concluded that CRP can stimulate the proliferation of MM cells
      directly by up-regulating the expression of survivin and HSP90alpha in MM cells.
      CRP can be regarded as a potential target for MM treatment.

PMID- 19840460
TI  - [Regulation of 2-methoxyestradiol-induced cell apoptosis by mcl-1 and bax genes
      in myelodysplastic syndrome].
AB  - The purpose of this study was to explore the mechanism underlying the regulation
      of 2-methoxyestradiol (2-ME)-induced cell apoptosis by mcl-1 and bax gene in
      myelodysplastic syndrome (MDS). The MUTZ-1 cells were pretreated with 2-ME; then
      the activity of caspases-3 was determined by fluorescent colorimetry; the mRNA
      expressions of apoptosis-related genes (mcl-1) and bcl-2-related X protein (bax)
      were determined by RT-PCR. The results showed that as compared with control, the
      2-ME enhanced the activity of caspase-3 in MUTZ-1 cells in a dose-and time
      dependent manners (p<0.05); along with increasing of 2-ME concentration, the
      expression of intracellular mcl-1 mRNA reduced (p<0.05), meanwhile the expression
      level of mcl-1 mRNA negatively correlated to the activity of caspase-3 at the
      corresponding time points (r=-0.992, p<0.01), but the expression of bax mRNA did
      not show significant change (p>0.05). It is concluded that 2-ME can regulate the
      apoptosis of MDS cells through the pathway of down-regulating the expression of
      mcl-1 mRNA and activating the caspase-3.

PMID- 19840461
TI  - [Quantitative analysis of dendritic cell subsets in bone marrow of patients with
      acute myeloid leukemia].
AB  - In order to study the quantity of dendritic cell (DC) subsets of bone marrow in
      patients with acute myeloid leukemia (AML), the bone marrow aspirate were
      collected from 77 newly diagnosed AML patients and from 30 healthy persons. The
      quantity of DC subsets (myeloid dendritic cells, mDC and plasmacytoid dendritic
      cells, pDC) were detected by flow cytometry and analysed by 3-color and 4-color
      cytometric gate. Based on the conventional 3-color panel, mDC were identified by
      Lin-HLA-DR+CD11c+ and pDC were identified by Lin-HLA-DR+CD123+. Based on the 4
      color panel, mDC were identified by Lin-HLA-DR+CD11c+ BDCA-1+ and pDC were
      identified by Lin-HLA-DR+CD123+BDCA-2+. The results showed that a reduction of
      mDC was found in 74.0% (57/77) and 58.4% (45/77) patients, a reduction of pDC was
      found in 90.9% (70/77) and 46.8% (36/77) patients respectively by 3-color and 4
      color cytometric analysis. Meanwhile an expansion of mDC was showed in 19.5%
      (15/77) and 22.1% (17/77) patients, an expansion of pDC was showed in 1.3% (1/77)
      and 27.3% (21/77) patients respectively by 3-color and 4-color cytometric
      analysis. In subtypes of AML-M2, AML-M3 or AML-M4/5, 81.4%, 100% and 42.1%
      patients showed mDC decrease and 88.4%, 100% and 89.5% patients showed pDC
      decrease respectively by 4-color cytometric analysis. It is concluded that the 4
      color cytometric gate is better method for detection of mDC and pDC from bone
      marrow of newly diagnosed AML patients as compared with 3-color cytometric gate,
      the majority of AML patients showed reduction of mDC and pDC. The percentages of
      patients with mDC normal or mDC increase in AML-M4/5 subtypes are more than that
      in AML-M2/3 subtypes, while the pDC does not show difference between AML
      subtypes.

PMID- 19840462
TI  - [Identification and enumeration of dendritic cells in peripheral blood and bone
      marrow of healthy individuals].
AB  - The study was aimed to analyse and enumerate the dendritic cells (DC) subsets in
      peripheral blood and bone marrow (BM) of healthy individuals in China by using 2
      panel 4-color flow cytometry (FCM). The percentage and absolute number of Lin-HLA
      DR+CD11chiBDCA1+ myeloid DC (mDC) and Lin-HLA-DR+CD123hiBDCA2+ plasmacytoid DC
      (pDC) were detected in 35 normal BM (NBM) and 29 normal peripheral blood (NPB),
      the results were compared with the Lin-HLA-DR+CD11chimDC and Lin-HLA-DR+CD123hi
      pDC obtained by 3-color FCM. The results indicated that both absolute count of DC
      subset and relative count of pDC in BM were decreased along with increase of age,
      the absolute count of DC subset in male BM was higher than that in femoral BM
      (p<0.05). The DC subsets in NBM and NPB were different whatever by 3 or 4-color
      cytometric analysis, there were more mDCs than pDCs in PB and the ratio of mDC to
      pDC was 2.70 and 2.31 respectively. In contrast, pDCs predominated in BM, the
      ratio of mDC to pDC in BM was 0.90 and 0.71 respectively. The quantity of DC
      subsets significantly correlated to both frequency (mDC r=0.86; pDC r=0.96,
      p<0.05) and absolute number (mDC r=0.95; pDC r=0.98, p<0.05) between 3 and 4
      color cytometric analysis. The quantity of DC subsets in PB and BM were
      significantly different, counted by 3 and 4-color cytometric analysis except pDC
      in PB (p<0.001). The quantity of DC subsets were much higher by 3-color than that
      by 4-color analysis. Since some Lin-HLA-DR+CD11chimDC and Lin-HLA-DR+CD123hi pDC
      were BDCA1- and BDCA-2dim/- respectively, that more were in BM than in PB. It is
      concluded that the DC absolute enumeration is correlated with sample type,
      gender, age and total nucleated cells (p<0.05). 4-color antibody combination may
      help to identify the real DC subsets in BM. DC subsets in NBM and NPB are
      different, that more mDC are in PB whereas more pDC in BM.

PMID- 19840463
TI  - [Investigation of uninterpretative HLA typing in 311 umbilical cord blood
      samples].
AB  - The aim of this study was to investigate the factors which affect HLA typing in
      311 umbilical cord blood (UCB) samples. The HLA low resolution typing of UCB
      samples with misinterpreted HLA types from 311 UCB samples analyzed by PCR-SSO
      and PCR-SSP was performed. 7 samples difficult to determine their HLA genotype
      were sequenced directly and the reason leading to misinterpret HLA typing was
      analyzed. The results indicated that 99.4% of misinterpreted samples resulted
      from the restriction of HLA typing method itself and 0.6% of misinterpreted
      samples were suspected to be contaminated with maternal blood in UCB. It is
      concluded that HLA typing is mainly affected by the shortcomings of
      oligonucleotide probe design for PCR-SSO and lack of allele specific primers of
      PCR-SSP.

PMID- 19840464
TI  - [High through-put genomic DNA isolation technique and its application in HLA
      genotyping for samples from bone marrow donor program].
AB  - This study was aimed to develop and establish an efficient method for high
      through-put automatically extracting genomic DNA from EDTA-anticoagulated whole
      blood samples, and to utilize this method in routine rSSO HLA genotyping by
      luminex flow array assay, the genomic DNA was extracted automatically from 400
      microl blood samples by using TECAN DNA workstation and 96-well plate with 2 ml
      volume per well. The yield and purity of each DNA sample was tested by UV
      spectrophotometer, the integrity of these DNA samples were run electrophoresis on
      the agarose gel. Each DNA sample was subjected to PCR amplification and
      hybridization using One lambda rSSO HLA-A, -B and -DRB1 commercial kit, the
      fluorescent intensity for positive bead and negative bead hybridized with HLA-A, 
      B and -DRB1 PCR products were calculated and analyzed. The results showed that
      the mean yield and purity (A260/A280) of genomic DNA extracted from 400 microl
      whole blood samples were 3.217+/-0.715 microg and 1.710+/-0.103 respectively. The
      molecular weight was more than 15 kb in size and the fluorescent intensity for
      positive bead hybridized with HLA-A, -B and -DRB1 PCR products of each sample was
      >600 RFU, however, the fluorescent intensity for negative bead for each sample
      was <50 RFU. It is concluded that the highly qualified genomic DNA can be
      extracted automatically from blood samples of marrow-donors by using TECAN DNA
      workstation, and the extracted DNA samples are suitable for high through-put HLA
      genotyping by luminex flow array assay and other downstream transplant
      immunological and molecular biological experiments.

PMID- 19840465
TI  - [Preparation and identification of monoclonal antibody against PNAS-2 protein].
AB  - This study was purposed to prepare and primarily identify the specific monoclonal
      antibodies (McAbs) against the apoptosis related protein PNAS-2 so as to provide
      the essential tool for study of PNAS-2 function. The McAbs against PNAS-2 were
      prepared via the immunization of mice, cell fusion and cloning using synthetic
      peptide of PNAS-2 as immunogen; the specificity, titer and subtype of McAb were
      detected by Western blot, ELISA and immunofluorescence. The results showed that
      the stable hybridoma cell line S-31-7 producing McAbs against PNAS-2 protein was
      successfully obtained. The immunoglobulin of the McAb was identified to be
      IGg1lambda. The titer of ascetic fluid fled McAb were 1:8,000. A single specific
      band with 28 kD was shown in Western blot test, and the antigen recognized was
      present in cell cytoplasm by immunofluorescence. In conclusion, the obtained McAb
      against PNAS-2 displays strong specificity and high titer, which may be applied
      to the advanced research on PNAS-2 protein.

PMID- 19840466
TI  - [Role of nitro oxide in immunosuppressive effect of human mesenchymal stem cells
      on allogenic proliferative response of lymphocytes].
AB  - The purpose of this study was to investigate the influence of nitro oxide (NO)
      from mesenchymal stem cells (MSC) on the proliferative responses of allogeneic
      lymphocytes and its mechanism. MSCs were isolated and cultured from human bone
      marrow. Selected surface antigens of MSCs were detected by flow cytometry and
      their morphologic characteristics were determined by microscopy. Mitomycin C
      treated MSCs were plated in dishes and then mixed lymphocyte cultures (MLC) were
      set up. After 4 days, lymphocyte proliferation was determined by CCK-8 assays; NO
      secretion in coculture supernatant was determined by Griess reagent kit; the
      level of FOXP3 mRNA expression was detected by real-time quantitative PCR. The
      results indicated that in MSC/MLC coculture experiment, the lymphocyte
      proliferation decreased significantly with of IOD value 0.49+/-0.03, NO
      production increased obviously (21.05+/-1.14 micromol/L) and FOXP3 mRNA
      expression was increased [(1.56+/-0.34)%] as compared with MLC coculture without
      MSC. There were significant difference between these two groups. It is concluded
      that NO production in human MSC culture up-regulates FOXP3 mRNA expression and
      thus inhibits lymphocyte proliferation response.

PMID- 19840467
TI  - [Adenovirus-delivered BMI-1 shRNA].
AB  - Recently, some plasmid vectors that direct transcription of small hairpin RNAs
      have been developed, which are processed into functional siRNAs by cellular
      enzymes. Although these vectors possess certain advantages over synthesized
      siRNA, many disadvantages exist, including low and variable transfection
      efficiency. This study was aimed to establish an adenoviral siRNA delivery system
      without above-mentioned disadvantages on the basis of commercially available
      vectors. A vector was designed to target the human polycomb gene BMI-1. The pAd
      BMI-1shRNA-CMV-GFP vector was produced by cloning a 300 bp U6-BMI-1 cassette from
      the pGE1BMI-1shRNA plasmid and a CMV-GFP cassette from pAdTrack CMV in pShutter
      vector. The adenovirus was produced from the 293A packaging cell line and then
      infected K562 cells. The mRNA and protein levels of Bmi-1 were detected by real
      time-PCR and Western blot respectively. The results showed that the adenovirus
      carrying the BMI-1shRNA was successfully produced. After being transfected with
      the adenovirus, the K562 cells dramatically down-regulated BMI-1 expression,
      whereas the adenoviruses carrying control shRNA had no effect on BMI-1
      expression. It is concluded that the adenoviruses are efficient vectors for
      delivery of siRNA into mammalian cells and may become a candidate vector carrying
      siRNA drugs for gene therapy.

PMID- 19840468
TI  - [Characteristics of fusion gene and immunophenotype in MLL gene rearrangement
      positive childhood acute lymphoblastic leukemia].
AB  - The study was aimed to investigate the fusion gene transcript and
      immunophenotypic characteristics of the mixed linage leukemia (MLL)-rearranged
      positive childhood acute lymphoblastic leukemia (ALL). The incidence of MLL
      rearrangement in 601 cases of ALL patients was detected by the multiple-nested
      polymerase chain reaction (PCR); the subtypes and features of the fusion gene
      transcript were analyzed by PCR products sequencing; the immunophenotypic
      characteristics at diagnosis were compared between the 22 MLL rearrangement
      positive of ALL patient, 30 negative control which selected randomly from the
      patients whose fusion gene could not be detected in the same term and 43 pro-B
      ALL patients. The results showed that the incidence of MLL positive ALL was
      3.66%, constituted 29.9% of the pro-B-ALL. The MLL rearrangement positive 20 B
      ALL patients were all CD10 negative; the number of patients who carried CD13,
      CD33 and CD34 was lower than that of pro-B-ALL who had no fusion gene, whereas
      the expression of CD20, CD22, CD2, CD5, CD7 showed no difference. 4 kind partner
      genes of MLL-AF4, AF9, AF10 and ENL were detected. The fusion loci of MLL gene
      were mainly located at the exon 6, 7, 8 and many kind of fusion loci of MLL may
      exist in one patient; whereas its partner gene fusion loci were relatively
      single. A transcript contains a random insert sequence existed in a transcript of
      one MLL-AF10+ patient. It is concluded that though incidence of MLL rearrangement
      is low, but it has a variety of fusion transcripts, the ALL patients has unique
      biological characteristics at immunophenotype and fusion transcript.

PMID- 19840469
TI  - [Therapeutic efficacy of bone marrow-derived mesenchymal stem cells infused into
      mice with liver injury induced by concanavalin A].
AB  - The aim of this study was to evaluate the therapeutic potential of bone marrow
      mesenchymal stem cells (MSC) on acute liver injury induced by concanavalin A
      (ConA). MSCs were isolated from male C57BL/6 mice and cultured, and a ConA
      induced acute liver injury model was used. MSCs were systemically infused
      immediately after mice were challenged with ConA, control mice received only
      saline infusion. 24 hours after MSC transplantation, the level of serum
      aminotransferases, histologic change and in situ apoptosis of cells were
      detected, the expression of inflammatory mediators were examined by real-time RT
      PCR. The results indicated that MSC transplantation significantly reduced ConA
      induced acute liver injury, including the decrease of the level of serum alanine
      aminotransferase (ALT), serum aspartate aminotransferase (AST) and the
      extenuation of liver necrosis and in situ apoptosis. Furthermore, after MSC
      infusion the expression of TNF-alpha, IFN-gamma in liver decreased greatly
      (p<0.05) with no statistical difference in the expression of iNOS, IL-2 and IL-10
      (p>0.05). It is concluded that the systemic infusion of MSCs can alleviate ConA
      induced acute liver injury in mice.

PMID- 19840470
TI  - [Comparative study of in vitro hematopoietic supportive capability of human
      mesenchymal stem cells derived from bone marrow and umbilical cord].
AB  - The present study was aimed to isolate and identify human mesenchymal stem cells
      from adult bone marrow (BM-MSC) and umbilical cord (UC-MSC), and to compare their
      ability to support in vitro long-term hematopoiesis. MSC from bone marrow and
      umbilical cord were isolated by using density gradient centrifugation or enzyme
      digestion. MSC were further purified by adherent culture. Immunophenotype,
      adipogenic and osteogenic differentiation potential of BM-MSC and UC-MSC were
      detected. The hematopoietic supporting capacity of BM-MSC and UC-MSC was assessed
      by LTC-IC assay. Nonadherent cells in each group were collected for phenotypic
      analysis at 3, 5 and 7th week of culture. The results showed that BM-MSC and UC
      MSC in culture shared a similar spindle-shaped morphology and adhered to the
      tissue culture substrate. They were both positive for CD90, CD105, CD73, CD29,
      CD54, CD166, HLA-ABC, and negative for HLA-DR, CD34 and CD45. BM-MSC and UC-MSC
      could differentiate into adipocytes or osteoblasts confirmed by oil red O
      staining and von Kossa staining, separately. LTC-IC assay showed that at 5th week
      of culture, the difference of the CFC yields between UC-MSC group and BM-MSC
      group was not statistically significant (p>0.05). At 6, 7, 9th week of culture,
      the CFC yields in the UC-MSC group were lower than those of BM-MSC (p<0.05). The
      phenotypic analysis of nonadherent cells at 3, 5, 7th week of culture indicated
      that along with prolongation of time, the percentages of CD34+ cells and CD117+
      cells in each group decreased markedly, and the percentages of CD33+ cells, CD13+
      cells and CD11b+ cells increased gradually. It is concluded that MSC from human
      adult bone marrow and umbilical cord can be successfully isolated and identified.
      UC-MSC are able to support long-term hematopoiesis in vitro, but its
      hematopoietic supportive capacity is weaker than those of BM-MSC.

PMID- 19840471
TI  - [Effect of mesenchymal stem cells on expression of CD69 in cord blood CIK/NK
      cells and quantity ratio of T regulatory cells in CIK/NK cell culture].
AB  - This study was purposed to explore the effect of bone marrow derived mesenchymal
      stem cells (MSCs) on the expression of CD69 on cytokine-induced killer
      (CIK)/natural killer (NK) cells derived from cord blood and on the quantity ratio
      of CD4+CD25+ T regulatory cells in CIK/NK cell culture system using Transwell non
      contact cell culture system. The experiments were divided into two groups:
      Transwell non-contact culture and mixture culture. The ratio of MSC to CIK/ NK
      cells was 1:20, 1:50 and 1:100. In mixture culture groups, MSC and CIK/NK cells
      were co-cultured by together contact as the same ratio of Transwell non-contact
      culture groups. The expression of CD69 on CIK/NK cells, as well as the quantity
      ratio of CD4+CD25+ T regulatory cells in CIK/NK cell culture were evaluated by
      flow cytometry. The results showed that the expression of CD69 on CIK/NK cells in
      experimental groups were significantly lower than that in control group
      (p<0.001). As to Transwell groups, CD69 expression on the CIK/NK cells at 1:20
      ratio of MSC and CIK/NK was significantly lower than that at 1:50 and 1:100
      ratio. There were no differences in the expression of CD69 on CIK cells in
      mixture groups with various MSC ratios, whereas the expression of CD69 on NK
      cells at 1:20 ratio was significantly lower than that at 1:50 and 1:100. The
      quantity ratio of CD4+CD25+ cells in CIK/NK cell culture system of experimental
      groups with MSC co-culture was significantly higher than that in control. As to
      Transwell groups, the ratio of CD4+CD25+ cells in CIK/NK cell culture system at
      1:20 and 1:50 was significantly higher than that at 1:100. The quantity ratio of
      CD4+CD25+ cells in CIK/NK cell culture system showed significant differences in
      various mixture groups. As to 1:20 ratio the amount of CD4+CD25+ cells in CIK/NK
      cell culture system of mixture groups was significantly higher than that in
      Transwell groups, while there were no differences of the quantity ratio of
      CD4+CD25+ cells in CIK/NK cell culture at 1:50 and 1:100. It is concluded that
      either by non-contact Transwell or mixed co-culture, the MSC can suppress the
      activation of allogeneic CB-CIK/NK cells, which maybe relate to up-regulating the
      ratio of CD4+CD25+ T regulatory cells in CIK/NK cell culture system in dose
      dependent manner.

PMID- 19840472
TI  - [In vivo tracing of transplanted bone marrow mesenchymal stem cells with
      bioluminescence imaging].
AB  - Mesenchymal stem cell (MSC)-based cell therapy has shifted into clinical trials
      to repair the damage of various tissues. In this setting, the survival of the
      transplanted cells contributes critically to the therapeutic effectiveness. To
      investigate the in vivo tracing of MSCs, a recombinant retroviral vector carrying
      firefly-luciferase reporter gene [pL (FLUC) SN] was constructed and several
      GPE+86 cell clones that stably expressed fluc were selected. The retroviral
      supernatants were collected and used to transfect MSC derived from C57 mice. The
      cells were then screened with G418 and the expression of the exogenous gene was
      identified by luciferase enzyme activity analysis. Labeled mouse MSCs (2x10(6))
      were injected into skeletal muscles, and the in situ expression was noninvasively
      tracked by in vivo bioluminescence imaging for 1, 3 and 6 days after
      transplantation. The results showed that the survival rates of the grafted cells
      dropped sharply with time, they were 57.2+/-11.7%, 8.6+/-2.5% and 5.4+/-3.1% on
      day 1, 3 and 6 after transplantation, and no fluorescent signals above background
      were detected on day 10. It is concluded that the method described above could be
      used for in vivo tracing of grafted cells. Furthermore, MSCs could not survive
      even transplanted into the none-ischemic skeletal muscles.

PMID- 19840473
TI  - [Effect of fetal lung mesenchymal stem cells on differentiation of umbilical cord
      blood mononuclear cells into megakaryocytes].
AB  - In order to analysis the effect of fetal lung mesenchymal stem cell (FL-MSC) on
      differentiation of umbilical cord blood mononuclear cells (MNC) into
      megakaryocytes, the fresh umbilical cord blood MNC were isolated and divided into
      2 groups in the culture added with TPO, IL-11 and heparin. In the first group MNC
      were cultured alone and in the second group MNC were cocultured with FL-MSC. The
      cells were collected at day 7, 10, 14 for cell counting and detection of CD41a
      and CD61 by flow cytometry. The morphology and ultrastructure of megakaryocytes
      were observed by immunohistochemistry method and transmission electron microscopy
      at day 14. The content of DNA was analyzed by flow cytometry at day 14 too. The
      results indicated that the of CD41a+ and CD61+ cells were obtained mostly in the
      second group at day 10 and were in 4.5 and 4.7 fold as much as the MNC cultured
      alone. The morphology and ultrastructure of megakaryocytes showed immature of
      nuclei in both of two groups. It is concluded that the FL-MSC could effectively
      enhance the production of CD41a+ and CD61+ cells, where the effect on nucleus
      development of the young megakaryocyte was not obviously shown.

PMID- 19840474
TI  - [Modulation of adhesion molecule expression on T cells in bone marrow after in
      vivo rhG-CSF application].
AB  - The aim of study was to investigate the modulation effect of recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) on adhesion molecule expression
      of memory T lymphocyte in the bone marrow grafts. rhG-CSF was administered in 41
      donors by subcutaneous injection for 5 consecutive days. Bone marrow grafts were
      collected on day 4. The percentages of CD4+ and CD8+, and the expressions of
      CD49d, CD54, CD62L and CD11a on donor T cells of steady state-bone marrow grafts
      (SS-BM, n=11) and rhG-CSF primed bone marrow (G-BM, n=30) were analyzed by using
      multi-color flow cytometry. The results indicated that the percentages of CD4+
      and CD8+ T cells were significantly lower in G-BM than those in SS-BM (p<0.05).
      There were no significant differences in the percentages of memory CD4+ and CD8+
      T cells between SS-BM and G-BM (p>0.05). The expressions of CD49d on CD4+ and
      CD8+T cells were significantly lower in G-BM than that in SS-BM (p<0.05).
      Compared with SS-BM, the expressions of CD54 on CD4+, memory CD4+ T cells and
      CD8+ T cells were significantly lower in G-BM (p<0.05). The expressions of CD62L
      on CD4+ and CD8+ T cells and memory T cells were all significantly lower in G-BM
      (p values were all less than 0.001). The expressions of CD11a on CD4+, memory
      CD4+ T cells were significantly lower in G-BM than that in SS-BM (p<0.05). There
      were no significant differences in the expression of CD11a on CD8+, memory CD8+ T
      cells between SS-BM and G-BM (p>0.05). It is concluded that the expression of
      cell adhesion molecules on the CD4+ and CD8+ T cells in G-BM is down-regulated
      after rhG-CSF treatment of healthy donors.

PMID- 19840475
TI  - [Clinical significance of TNF-alpha, IL-1beta and IFN-gamma levels at early phase
      after allogeneic hematopoietic stem cell transplantation].
AB  - The objective of this study was to investigate the alterations of cytokines TNF
      alpha, IL-1beta and IFN-gamma at early phase after allogeneic hematopoietic stem
      cell transplantation and in the course of preconditioning, and to explore the
      relation of these cytokines with transplant-related complications. Alterations of
      TNF-alpha, IL-1beta, and IFN-gamma levels in serum were detected by ELISA in 95
      patients received allogeneic hematopoietic stem cell transplantation (among them
      43 cases with GVHD, 5 cases with thrombosis, 31 cases with infection) and 20 in
      healthy adults. Alterations of the three cytokines were analyzed during the
      preconditioning and the early phase after transplantation. The results showed
      that the TNF-alpha levels in aGVHD patients underwent allo-HSCT were already
      higher than that in normal controls before preconditioning (p<0.01), other
      patients did not show significant change during this course. TNF-alpha level in
      all patients were higher than that at day 4 of preconditioning, then decreased at
      end of preconditioning (p<0.05). TNF-alpha level increased at occurrence of
      aGVHD, thrombosis and infection, which is most significant in patients with
      aGVHD, and less significant in patients with infection as compared with patients
      with thrombosis (p<0.05). TNF-alpha level began to increase at 2 weeks before
      aGVHD and thrombosis developed in patients, while TNF-alpha levels did not change
      in patients with infection at the same time. IL-1beta levels did not change
      during preconditioning, but increased at time of aGVHD, thrombosis and infection
      in patients, in which IL-1beta levels in patients with thrombosis increased
      obviously, and more obviously in patients with aGVHD than that in patients with
      infection (p<0.01). IL-1beta levels in patients with aGVHD began to increase at 1
      week before aGHVD developed, but IL-1beta levels in patients with thrombosis
      began to increase at two weeks before complication developed. IFN-gamma levels
      did not change in all patients during the process of transplantation. It is
      concluded that the alterations of cytokine levels exist during the course of allo
      HSCT, which reflects the vascular damage following preconditioning and occurrence
      of some transplant associated complications. Levels of TNF-alpha and IL-1beta are
      closely related to aGVHD or thrombotic complications. Monitoring changes of TNF
      alpha and IL-1beta levels contributes to early discovery of aGVHD and thrombotic
      complications.

PMID- 19840476
TI  - [Clinical study of haploidentical peripheral blood stem cell transplantation
      without ex vivo T-cell depletion for high-risk hematological malignancies].
AB  - This study was aimed to explore the efficacy and associated complications of
      haploidentical peripheral blood stem cell transplantation (hi-PBSCT) without ex
      vivo T-cell depletion in treatment of hematological malignancies. 15 high-risk
      patients received HLA 1-3 loci (A, B, or DRB1) mismatched hi-PBSCT. The modified
      Bu/Cy or TBI/Cy regimen was used for preconditioning of patients. The anti
      thymocyte globulin, cyclosporin A, methotrexate and mycophenolate mofetil were
      used for GVHD prophylaxis. 4 cases were administrated with anti-CD25 monoclonal
      antibody. G-CSF-mobilized peripheral blood stem cells were infused, with the
      median number of infused nucleated cells was 8.16 (3.92-10.86)x10(8)/kg and that
      of CD34+ cells was 4.51 (1.27-5.95)x10(6)/kg. The results showed that the rapid
      engraftment was observed in all cases. The median times of neutrophil
      recovery>or=0.5x10(9)/L and platelet recovery>or=20x10(9)/L were 14 (11-19) and
      22 (11-52) days after transplantation respectively. 6 cases developed acute GVHD
      of grade I-II, and 2 cases experienced chronic extensive GVHD. Infection within
      100 days after hi-PBSCT was documented in all cases. 8 cases were subjected to
      bacterial infection, and six got cytomegalovirus infection. Relapse occurred in
      five cases. Overall survival of patients was 46.7% (7/15), with a median follow
      up of 213 (42-589) days. In conclusion, hi-PBSCT provides an effective
      alternative treatment for high-risk patients in lack of matched donors, and to
      reduce the high transplantation-related mortality.

PMID- 19840477
TI  - [Haploidentical allogeneic bone marrow stem cell transplantation combined with
      peripheral blood stem cells for therapy of leukemia].
AB  - The purpose of this study was to investigate the feasibility and clinical outcome
      of granulocyte colony stimulating factor (G-CSF)-mobilized haploidentical bone
      marrow transplantation combined with peripheral blood stem cells (hiBM+PBSCT) for
      therapy of leukemia. 125 leukemia patients underwent G-CSF primed haploidentical
      stem cell transplantation without ex-vivo T cell depletion. All haploidentical
      donors were injected with G-CSF at dose of 5 microg/(kg.d) for 7 days. The
      patients were divided into groups A and B. 29 patients in group A underwent
      hiBM+PBSCT at 7th and 8th days of mobilization in donors with G-CSF respectively;
      96 patients in group B underwent hiBMT. All patients received the same GVHD
      prophylaxis regimen, the clinical outcomes were investigated. The results showed
      that all patients except one CML-myelofibrosis patient achieved trilineage
      engraftment. Engraftment median times were 15 and 19 days for neutrophil and
      platelet in group A respectively, while engraftment median times were 18 and 23
      days for neutrophil and platelet in group B respectively. The incidences of grade
      II-IV aGVHD were 31.03% in group A and 12.5% in group B respectively (p<0.05).
      The incidences of grade III-IV aGVHD was 13.79% and 10.41% in group A and group B
      (p>0.05). The aGVHD-related death incidence was 3.45% and 5.21% in group A and
      group B (p>0.05). The incidence of grade II-IV cGVHD was 48.2% and 35.4% in group
      A and group B respectively (p>0.05). The incidence of extensive cGVHD was 23.3%
      and 15.6% in group A and group B respectively (p>0.05). The disease relapse rate
      was 6.8% (2/29) and 18.75% (18/96) in group A and group B respectively (p<0.05).
      It is concluded that the G-CSF-mobilized allogeneic haploidentical BM plus
      peripheral blood HSCT without T cell depletion provides a rapid and sustained
      engraftment without increase of severe GVHD, furthermore, the relapse rate of
      disease is reduced remarkably, thus this method can be used in clinic.

PMID- 19840479
TI  - [Nocardial infection after allogeneic hematopoietic stem cell transplantation].
AB  - In order to explore the diagnosis and therapeutic effectiveness of nocardiosis
      after allogenic hematopoietic stem cell transplantation (allo-HSCT), the features
      of clinical manifestation, laboratory examination and response to TMP-SMZ
      treatment in two cases of nocardiosis after allo-HSCT were analyzed
      retrospectively. The result showed that the attack happened to 2 patients at day
      15 and 170 after allo-HSCT respectively, displaying fever and chest pain. Chest
      CT scan indicated bilateral pulmonary tuberculous shadow. Nocardiosis was
      diagnosed by the culture of sputum, bronchoalveolar lavage (BAL) fluid and pus
      samples as well. Both of these cases exhibited good response to combined therapy
      containing TMP-SMZ for half a year. It is concluded that nocardiosis is a rare
      complication after allo-HSCT, in which pulmonary involvement is commonly
      observed. The culture of BAL fluid is helpful for its diagnosis and this disease
      might be sensitive to the treatment of TMP-SMZ-containing regimens.

PMID- 19840478
TI  - [Effect of FLAG consolidation therapy on mobilization of autologous peripheral
      blood stem cells in patients with acute myelogenous leukemia].
AB  - This study was aimed to investigate the effect of FLAG consolidatory therapy on
      peripheral blood stem cell (PBSC) mobilization in patients with acute myelogenous
      leukemia (AML) for autologous PBSC transplantation. A total of 15 AML patients
      were enrolled in this study. 10 patients were male, and 5 were female, with ages
      ranging from 14 to 51 (median 36) years. Out of 15 patients 13 were newly
      diagnosed, and 2 were refractory/relapsed AML. All patients were consolidated
      with FLAG regimen which including fludarabine 50 mg/d, days 1-5; Ara-C 2
      g/(m2.d), days 1-5; G-CSF 300 microg/d, injection subcutaneously starting 24
      hours before Ara-C and continuing until neutrophil count exceeding 1.0x10(9)/L.
      The harvest of the stem cells was performed after hematologic recovery from the
      second or third course of FLAG consolidation, or mobilized by high dose etoposide
      (1.6 g/m2). The results showed that among 15 patients scheduled for PBSC harvest,
      11 (73.3%) harvested a median of 3.52x10(6)/kg CD34+ cells (range 2.2-4.6) and
      underwent autologous transplantation, while the minimal number of CD34+ cells
      could not be reached in the remaining 4 patients. It is concluded that the FLAG
      regimen is effective and well-tolerated treatment as consolidation regimen in
      AML, which does not influence PBSC mobilization and autologous transplantation
      after 2 courses of FLAG.

PMID- 19840480
TI  - [Clinical study on regimen cyclophosphamide, Ara-C and topotecan (CAT) in
      treatment of patients with refractory or relapsed acute myelogenous leukemia].
AB  - Up to now, no consensus has been reached on the standard salvage regimen for
      patients with refractory or relapsed acute myeloid leukemia (AML). This study was
      purposed to evaluate the efficacy and safety of combination chemotherapy
      composing of cyclophosphamide (Cy), cytosine arabinoside (Ara-C) and topotecan
      (CAT regimen) for 37 refractory or relapsed AML patients. The dosing regimen was
      as follows: Cy 300 mg/m2 by intravenous infusion, every 12 hours on days 1-3,
      topotecan 1.25 mg/m2 by intravenous continuous infusion over 6 hours daily on
      days 2 to 6, Ara-C 500 mg/m2 by intravenous infusion over 2 hours daily for 5
      days on days 2-6. The results showed that all patients completed one cycle of
      chemotherapy. 12 patients (32.4%) achieved complete remission (CR), 2 (5.4%)
      achieved partial remission (PR), and the 23 remaining patients achieved no
      remission (NR). The overall response rate (RR) was 37.8%. Among 18 relapsed
      cases, 6 cases had CR (33.3%), 2 cases achieved PR (11.1%), and 10 cases were
      with NR (55.6%). Among 19 refractory cases, 6 had CR (31.6%), and 13 (68.4%) were
      with NR. There was no statistically significant difference in RR between
      refractory and relapsed groups (31.6% and 44.4%, respectively) (p=0.42).
      Myelosuppression was universal. Mild non-hematologic toxicities were mainly
      gastrointestinal, as nausea, vomiting, diarrhea. The incidence of severe (grade
      III-IV) non-hematologic toxicity, such as oral mucositis and infection was 37.8%
      and 86.5% respectively. Only one patient died of severe infection during the
      observation (within 28 days from start of chemotherapy). The time of median
      follow-up was 4 (0-33) months, the median overall survival (OS) was 4 (1.8-6.2)
      months. The median OS for responders was longer than that for non-responders (9
      vs 2 months respectively, p=0.00). In conclusion, the CAT regimen of lower dose
      is well tolerated and has certain anti-leukemia effect, and worthy to be further
      investigated.

PMID- 19840481
TI  - Natural killer/T cell lymphoma initiating with pleural effusion: the significance
      of MICM combined techniques for the diagnosis.
AB  - Natural killer (NK)/T-cell lymphomas represent a rare type of lymphoma derived
      from either activated NK cells or cytotoxic T cells. They are most commonly
      extranodal and tend to present as destructive lesions within the midline facial
      structures. Other than the nasal cavity and Para nasal sinuses, several other
      extra nodal sites of involvement have been reported, including the pharynx,
      gastrointestinal tract, and testis. Occasionally, pleural effusion has also been
      observed. Here, a case of lymphoma of NK/T-cell type presented as pleural
      effusion was reported. The patient was previously misdiagnosed as B cell non
      Hodgkin's lymphoma by pathological and immunohistochemistry (IH) analysis for
      pleural membrane biopsy specimen. After the analysis of the pleural fluid cells
      by a combination of morphologic, immunophenotypic, cytogenetic and molecular
      (MICM) methods in Beijing Dao-Pei hospital, some lymphoblasts were found
      morphologically, which expressed cytoplasmic CD3 (cCD3) and CD56 by flow
      cytometry analysis and had a clonal T-cell receptor gamma (TCR-gamma) gene
      rearrangement by molecular analysis, so that the diagnosis was finally corrected
      as NK/T-cell lymphoma and an allogeneic stem cell transplantation was
      successfully performed. In conclusion, this unusual case highlights the
      significance of MICM combined techniques for the diagnosis of lymphoma, as well
      as an unusual presentation of a rare disease and the successful treatment.

PMID- 19840482
TI  - [Clinical analysis of 14 patients with lymphoma associated hemophagocytic
      syndrome].
AB  - The study was aimed to investigate the clinical characteristics, diagnosis and
      therapy of patients with lymphoma associated hemophagocytic syndrome (LAHS) so as
      to provide the clinical basis for improving its recognition and giving effective
      therapy. The clinical data of 14 patients with LAHS in Beijing Friendship
      Hospital, Capital Medical University during the period from June 2005 to May 2008
      were collected, the informations including primary diseases, clinical
      manifestations, laboratory findings, therapy and outcome were analyzed
      retrospectively, the coincidence of each diagnostic index was compared before and
      after diagnosis. All 14 patients were given therapeutic regimens containing
      fludarabine, methylprednisolone and gammaglobulin (FDIg) after final diagnosis.
      The results indicated that 100% patients had abnormal changes on NK cell activity
      and sCD25 level in serum, but hemophagocytosis in less than 40% patients at early
      stage was found in bone marrow. Even after confirmed diagnosis of the disease,
      the percentage of patients with hemophagocytosis was not up to 50%. 9 out of the
      14 patients had a good prognosis after treatment, and the other 5 patients died.
      It is concluded that the detection of NK cell activity and sCD25 level in serum
      may be valuable for the early diagnosis of LAHS, the hemophagocytosis is not
      necessary for the diagnosis of LAHS. Fludarabine combined with methylprednisolone
      and gamma globulin may provide a new strategy for LAHS therapy.

PMID- 19840483
TI  - [Preliminary clinical analysis of the hepatic dysfunction in patients with
      acquired hemophagocytic lymphohistiocytosis].
AB  - The aim of this study was to investigate the clinical features of acquired
      hemophagocytic lymphohistiocytosis (HLH) complicated with hepatic dysfunction. 18
      cases of acquired HLH were analyzed. The characteristics of hepatic dysfunction,
      the relationship between hepatic dysfunction and the cause, as well as prognosis
      of the acquired HLH were preliminarily analysed. The results indicated that
      characteristics of hepatic dysfunction in acquired HLH patients were
      hypoproteinemia, jaundice and increase of L-aspirate aminotransferase (AST) and
      lactate dehydrogenase (LDH) levels. The level of AST and direct bilirubin (DBil)
      in the non-malignancy associated hemophagocytic lymphohistiocytosis group were
      higher than that in malignancy-associated hemophagocytic lymphohistiocytosis
      group (p<0.05). And the increase of LDH and AST levels indicated poor prognosis
      (p<0.05). In conclusion, liver damage is a common organ functional disorder in
      patients with acquired HLH, which may be correlated to the cause and the
      prognosis of acquired HLH.

PMID- 19840484
TI  - [Effects of sodium ozagrel in primary thrombocytosis combined with thrombosis].
AB  - This study was aimed to investigate the incidence of thrombosis in patients with
      primary thrombocytosis (PT) and its correlation with function changes of
      platelets, and to explore the effect of thromboxane A2 (TXA2) inhibitor-ozagrel
      sodium on platelet activity and its efficacy for prevention and treatment of
      thrombosis. The CD62P and PAC-1 levels on platelet surface were detected by flow
      cytometry; the levels of TXB2 (metabolic product of TXA2) and 6-keto-PGFIalpha
      (metabolic product of prostacyclin) were detected by FLISA. The function change
      of platelets and its correlation with thrombosis were observed and compared in PT
      patients with and without thrombosis. The results indicated that the TXB2, PAC-1
      and CD62P level, and TXB2/6-keto-PGF1alpha ratio in PT patients with thrombosis
      were higher than those in PT patients without thrombosis before treatment with
      ozagrel sodium (p<0.01). After treatment with ozagrel sodium, the function
      indexes of platelets such as CD62P, PAC-1, TXB2 and TXB2/6-keto-PGF1alpha except
      6-keto-PGF1alpha in PT patients with and without thrombosis decreased obviously
      (p<0.01), but there was no significant difference in TXB2, 6-keto-PGF1alpha and
      TXB2/6-keto-PGF1alpha levels between PT patients with and without thrombosis
      except CD62P and PAC-1. It is concluded that the multi-index of platelets in PT
      patients with thrombosis are higher than that in PT patients without thrombosis,
      the activation of platelet function is a high risk factor for thrombosis of PT
      patients. The ozagrel sodium can obviously reduce the platelet activation,
      decrease the production of TXA2 and ameliorate the TXB2/6-keto-PGF1alpha ratio.
      The ozagrel sodium not only possesses therapeutic effect, but also preventive
      efficacy for thrombosis.

PMID- 19840485
TI  - [Establishment of genotyping method for fetal ABO group from pregnant maternal
      peripheral blood].
AB  - This study was aimed to establish a genotyping method to detect ABO group gene of
      fetus from peripheral blood of pregnant women for prenatal diagnosis of hemolytic
      disease of newborn (HDN) resulting from ABO blood group incompatibility. 4 pairs
      of primers were designed according to ABO blood group gene DNA and mRNA
      sequences. 20 plasma DNA samples from healthy donors were extracted and amplified
      to explore the best conditions for plasma DNA extraction and PCR amplification.
      The O group plasma DNA was mixed with A group or B group plasmas by the ratios of
      1:1, 2:1, 4:1, 8:1, 10:1, 20:1, 40:1, 100:1 to simulate the status of mixed ABO
      gene from pregnant maternal blood and to establish the mixed blood group ABO
      genotyping technology. The pregnant maternal blood samples with more than 30
      weeks of gestation were selected for detecting the fetal ABO blood group
      genotype. The blood samples should be taken as possible as after birth for
      identification of ABO blood group and evaluation of sensitivity and accuracy of
      fetal ABO blood group genotyping technology through peripheral blood of pregnant
      women. The results indicated that the minimal amount of template DNA from single
      blood plasma for accuracy identification was at least about 0.625 ng, the DNA
      amount extracted from 500 microl of plasma could meet the requirement for PCR
      amplification. When the proportion of O group plasma DNA in mixed plasma DNA was
      <or=10, the non-O group gene could be accurately detected. Among 14 peripheral
      blood samples from O-group pregnant women, the non-O group gene was amplified in
      9 samples; the non-O group gene was not amplified in 5 samples. The
      identification of peripheral blood ABO group for 5 newborns using serologic
      method showed that the A group 3 cases, B group 2 cases, O group 1 case, which
      consisted with genotyping results with consistent rate 100%. It is concluded that
      in middle and late pregnancy the fetal ABO group gene can be detected accurately
      by means of established fetal ABO group gene extraction and typing technology,
      that provides some guidances for the prenatal diagnosis and prevention of HDN.

PMID- 19840486
TI  - [Optimization of composition and concentration for lyophlizing protectant of
      human red blood cells].
AB  - This study was purposed to investigate the effect of different compositions and
      concentrations of lyophilizing protectants on recovery of RBCs and hemoglobin
      (Hb) after rehydration of lyophilized RBCs. The RBC lyophilizing protectants
      composed of a series concentrations of PVP, trehalose and different osmotic
      protectants were applied for protecting lyophilizing process of RBCs, the
      recovery of RBCs and Hb after rehydration of lyophilized RBCs was detected. The
      results showed that there were significant differences in loss ratio of RBCs
      between protectants composed of different compositions and concentrations (p<0.05
      or p<0.01). The loss ratio of RBCs in protectant containing 30% PVP40, 150 mmol/L
      trehalose and 2% BSA was minimum (0.02%), the loss ratio of RBCs in protectant
      containing 6% PVP 360, 100 mmol/L trehalose and 2% BSA was maximum (0.27%). The
      difference of effect between 150 and 50 mmol/L trehalose was statistically
      significant (p<0.01). The recovery rates of RBCs and Hb in protectants contained
      PVP40 of different concentrations were different after rehydration of lyophilized
      RBCs. The protectant containing 15% PVP40, 150 mmol/L trehalose and 2% BSA showed
      optimal protective efficacy for lyophilized RBCs, the recovery rates of RBCs and
      Hb were 61.29+/-4.11% and 62.49+/-5.91% respectively, which were statistically
      different from other protectants (p<0.01). The protectants containing glycerol
      displayed best efficiency in lyophilization too, the recovery rates of RBCs and
      Hb were 65.97+/-4.52% and 67.24+/-5.94%, respectively. It is concluded that the
      protectants composed of 0.8 mol/L glycerol, 15% PVP40, 150 mmol/L trehalose and
      2% BSA (pH 7.3 ) may be used as the protectant lyophilizing human RBCs in future
      study.

PMID- 19840487
TI  - [Protection of cryopreserved platelets by dimethyl sulfoxide combined with
      trehalose].
AB  - This study was aimed to investigate the protective effects of dimethylsulfoxide
      (DMSO) combined with trehalose on the cryopreserved platelets. The platelets were
      preserved at -80 degrees C. The experiments were divided into 5 groups: blank
      control group composed of apheresis platelet suspension; trehalose group composed
      of apheresis platelet suspension and 0.25 mol/L trehalose; DMSO group composed of
      apheresis platelet suspension and 5% DMSO; 5% combined group composed of
      apheresis platelet suspension, 5% DMSO and 0.25 mol/L trehalose; 2.5% combined
      group composed of apheresis platelet suspension, 2.5% DMSO and 0.25 mol/L
      trehalose. All the groups were thawed at 37 degrees C in a waterbath. The
      recovery rate of platelets and mean platelet volume (MPV) were assayed by using
      hemocytometer; the ultrastructural changes were examined by electron microscopy;
      the expressions of CD41, CD42b, CD61 and CD62p on platelets were detected by flow
      cytometry. The results indicated that single use of trehalose had no strong
      effect in increasing the recovery rate of platelets, but the morphology of
      platelets was close to normal. The DMSO showed significant effect in increasing
      the recovery rate of platelets and maintaining the intact property of platelets,
      however, the shape of platelets tended to sealing, and partial platelets still
      displayed heteromorphic changes. The combination of DMSO and trehalose revealed
      the protective effect on the external morphology and internal structure of
      platelets to be close to the normal homeostasis, and ensured an ideal recovery
      rate of the cryopreserved platelets and higher expression levels of CD41, CD42b,
      CD61 and CD62p in the same time. It is concluded that the combined use of DMSO
      and trehalose possesses the synergistic protective effect on the cryopreserved
      platelets, therefore, the combined use of both as the protective agent is hopeful
      to further raise the effectiveness of clinical infusion of the cryopreserved
      platelets.

PMID- 19840488
TI  - [Notch signaling pathway and multiple myeloma].
AB  - Notch signaling pathway is a main pathway through cell-cell interactions, which
      regulates the programmed cell death, cellular proliferation and differentiation
      in multiple cell systems, and also is an important signaling pathway to modulate
      the balance between proliferation and differentiation in hematopoietic
      environment, and is related with the incidence of multiple hematologic
      malignancies. Multiple myeloma (MM) is malignant in B cell lineage and
      characterized by clonal proliferative plasma cells. It is very difficult to cure
      MM patients with a low proliferation rate of the MM cell and drug resistance to
      the standard dosage of chemotherapy. In recent years, research has shown that in
      the malignant plasma cells of the patients with multiple myeloma (MM) and the
      cell lines, but not in normal plasma cells or tumor cells from patients with
      other malignancies, the Notch ligand Jagged2 was found to be overexpressed.
      Jagged2 can induce stromal cells to secrete IL-6, VEGF and IGF-1. Notch
      activation can interact with NF-kappaB and C-myc to promote the proliferation and
      to inhibit the apoptosis of MM cells, showing in the relationship between the
      incidence of myeloma and drug resistance. Inhibition of the Notch signaling
      pathway may induce the apoptosis of MM cells and enhance the effect of
      chemotherapy. Study indicated that the specific inhibition of Notch signaling by
      treatment with a gamma-secretase inhibitor (GSI) alone, a specific pharmacologic
      inhibitor of Notch signaling, induces the apoptosis of myeloma cells and improves
      sensitivity of myeloma cell to chemotherapy when combined. In this article the
      composition of Notch signalling pathway, the mechanism of Notch signalling
      pathway and the relation of Notch signalling pathway to multiple myeloma were
      reviewed.

PMID- 19840489
TI  - [Advances of studies on T follicular helper cells].
AB  - T follicular helper cells (TFH cells) provides a helper function to B cells. It
      is one of the most important subsets of effector T cells in lymphoid tissues. The
      features of TFH cells include chemokine receptor expression (CXCR5),
      location/migration (B cell follicles), and function (B cell help). TFH cells
      produce a "helper" cytokine-IL-21, which can stimulate B cells to differentiate
      into Ab-forming cells through IL-21R. Dysregulation of TFH cell function likely
      contributes to the pathogenesis of immune-related diseases. In this article, the
      discovery of CXCR5 and TFH cells, origin of TFH cells, cytokines related with TFH
      cell function, migration and location of TFH effector cells and memory cells as
      well as dysregulation of TFH cell function and related diseases were reviewed.

PMID- 19840490
TI  - [Advance of study on animal models of lymphoma].
AB  - Lymphoma is a kind of malignant tumors that takes place in the lymphoid and
      hematological system. It is important to establish appropriate and stable animal
      models of lymphoma and they are useful for the experimental research of
      mechanisms and efficient treatment of disease. In this article the establishment
      methods, characteristics and practical use of various animal models of lymphoma
      were reviewed.

PMID- 19840491
TI  - [Advances of research on demethylation therapy for hematologic malignancies].
AB  - DNA methylation is an important and reversible epigenetic modification which
      regulates genomic stability. Methylation is essential for mammalian development.
      Generally, gene expression level and DNA methylation are negative correlation.
      Transcriptional silencing via methylation of CpG islands in the promoter is
      important for cell growth and differentiation and plays a key role in
      tumorigenesis. Demethylation drug can modify chromatin and restore the ability of
      anti-oncogene. Demethylation therapy as a new therapy may treat efficiently
      hematological malignancies with resistance and relapse. In this review, DNA
      methylation mechanism, relationship between aberrant methylation and hematologic
      malignancies, mechanism of demethylation therapy, the advance of research on the
      demethylation therapy of hematological malignancies, such as acute and chronic
      leukemia, lymphoma, myelodysplastic syndrome were summarized.

PMID- 19840492
TI  - Testing multivariate mean collinearity via latent variable modelling.
AB  - A procedure for testing mean collinearity in multidimensional spaces is outlined,
      which is applicable in settings with missing data and can be used when examining
      group mean differences. The approach is based on non-linear parameter
      restrictions and is developed within the framework of latent variable modelling.
      The method provides useful information about the constellation of multiple
      response centroids in the populations studied, and is illustrated with an
      example.

PMID- 19840493
TI  - Acquiescence as a source of bias and model and person misfit: a theoretical and
      empirical analysis.
AB  - In personality and attitude measurement, the presence of acquiescent responding
      can have an impact on the whole process of item calibration and test scoring, and
      this can occur even when sensible procedures for controlling acquiescence are
      used. This paper considers a bidimensional (content acquiescence) factor-analytic
      model to be the correct model, and assesses the effects of fitting unidimensional
      models to theoretically unidimensional scales when acquiescence is in fact
      operating. The analysis considers two types of scales: non-balanced and fully
      balanced. The effects are analysed at both the calibration and the scoring
      stages, and are of two types: bias in the item/respondent parameter estimates and
      model/person misfit. The results obtained theoretically are checked and assessed
      by means of simulation. The results and predictions are then assessed in an
      empirical study based on two personality scales. The implications of the results
      for applied personality research are discussed.

PMID- 19840494
TI  - Empirically indistinguishable multidimensional IRT and locally dependent
      unidimensional item response models.
AB  - Multidimensionality is a core concept in the measurement and analysis of
      psychological data. In personality assessment, for example, constructs are mostly
      theoretically defined as unidimensional, yet responses collected from the real
      world are almost always determined by multiple factors. Significant research
      efforts have concentrated on the use of simulated studies to evaluate the
      robustness of unidimensional item response models when applied to
      multidimensional data with a dominant dimension. In contrast, in the present
      paper, I report the result from a theoretical investigation that a
      multidimensional item response model is empirically indistinguishable from a
      locally dependent unidimensional model, of which the single dimension represents
      the actual construct of interest. A practical implication of this result is that
      multidimensional response data do not automatically require the use of
      multidimensional models. Circumstances under which the alternative approach of
      locally dependent unidimensional models may be useful are discussed.

PMID- 19840495
TI  - Mastectomy, body deconstruction, and impact on identity: a qualitative study.
AB  - OBJECTIVES: This qualitative study aims at understanding the consequences of body
      deconstruction through mastectomy on corporality and identity in women with
      breast cancer. DESIGN: Nineteen women were contacted through the hospital. All
      had to undergo mastectomy. Some were offered immediate breast reconstruction,
      others, because of cancer treatments, had no planned reconstruction. A
      qualitative reflexive methodological background was chosen. METHOD: Women were
      invited to participate in three semi-structured interviews, one shortly before or
      after mastectomy, and the other interviews later in their illness courses, after
      surgery. All interviews were transcribed verbatim. Thematic analysis was
      performed. The analysis of the first interview of each woman is presented in this
      article. RESULTS: Mastectomy provokes a painful experience of body
      deconstruction. Even when immediate reconstruction is proposed, contrasted
      feelings and dissonance are expressed when comparing the former healthy body to
      the present challenged body entity. Body transformations are accompanied with
      experiences of mutilation, strangeness, and modify the physical, emotional
      social, symbolic and relational dimensions of the woman's gendered identity.
      Although the opportunity of breast reconstruction is seen as a possible recovery
      of a lost physical symmetry and body integrity, grieving the past body and
      integrating a new corporality leads to a painful identity crisis. CONCLUSION:
      With mastectomy, the roots of the woman's identity are challenged, leading to a
      re-evaluation of her existential values. The consequences of mastectomy transform
      the woman's corporality and embodiment, and question her identity. Psychological
      support is discussed in the perspective of our results.

PMID- 19840497
TI  - Point of Care. How do I perform a first dental visit for an infant or toddler?

PMID- 19840496
TI  - Emotion suppression affects cardiovascular responses to initial and subsequent
      laboratory stressors.
AB  - OBJECTIVE: The study of anger suppression and risk for cardiovascular disease has
      relied predominately on inspection of correlations between trait anger-in and
      cardiovascular risk factors and disease. This approach tells us little about
      whether inhibitory processes have anything to do with outcomes, and cannot speak
      to whether suppression of anger per se affects cardiovascular parameters. Drawing
      on the broader emotion regulation literature, we examined the effects of
      experimentally induced anger and general negative emotion in the context of
      expressive and experiential suppression on cardiovascular responses to initial
      and subsequent laboratory stressors. DESIGN: Of all participants, 201 healthy
      participants were randomly assigned to one of six conditions formed by crossing
      emotion (anxiety, anger) and suppression (experiential, expressive, control)
      conditions. METHODS: Participants completed a mental arithmetic task with anxiety
      or anger induction under their respective suppression manipulation instructions,
      and subsequently were exposed to a cold pressor task. Systolic blood pressure
      (SBP), diastolic blood pressure, and heart rate values were obtained for each
      experimental epoch. RESULTS: More robust SBP responses to the initial stressor
      were evidenced for those in the expressive versus the control condition. In
      response to the subsequent stressor, those in the experiential suppression
      condition showed the most pronounced SBP responses, suggesting pronounced delayed
      effects of this type of suppression. Effects of suppression on SBP reactivity
      were indistinguishable across anxiety and anger conditions. CONCLUSION: Effortful
      suppression of negative emotion has immediate and delayed consequences for stress
      induced cardiovascular reactivity. Theoretical and clinical significance of these
      findings are discussed.

PMID- 19840498
TI  - Point of Care. How do I manage a suspected oral vascular malformation?

PMID- 19840499
TI  - Retrospective review of voluntary reports of nonsurgical paresthesia in
      dentistry.
AB  - OBJECTIVE: Paresthesia is an adverse event that may be associated with the
      administration of local anesthetics in dentistry. The purpose of this
      retrospective study was to analyze cases of paresthesia associated with local
      anesthetic injection that were voluntarily reported to Ontario"s Professional
      Liability Program (PLP) from 1999 to 2008 inclusive, to see if the findings were
      consistent with those from 1973 to 1998 from this same source. MATERIALS AND
      METHODS: All cases of nonsurgical paresthesia reported from 1999 to 2008 were
      reviewed; cases involving surgical procedures were excluded. Variables examined
      included patient age and gender, type and volume of local anesthetic, anatomic
      site of nerve injury, affected side and pain on injection or any other symptoms.
      RESULTS: During the study period, 182 PLP reports of paresthesia following
      nonsurgical procedures were made; all but 2 were associated with mandibular block
      injection. There was no significant gender predilection, but the lingual nerve
      was affected more than twice as frequently as the inferior alveolar nerve. During
      2006-2008 alone, 64 cases of nonsurgical paresthesia were reported to PLP, a
      reported incidence of 1 in 609,000 injections. For the 2 local anesthetic drugs
      available in dental cartridges as 4% solutions, i.e., articaine and prilocaine,
      the frequencies of reporting of paresthesia were significantly greater than
      expected (chi2, exact binomial distribution; p < 0.01) based on their level of
      use by Ontario dentists. These data suggest that local anesthetic neurotoxicity
      may be at least partly involved in the development of postinjection paresthesia.

PMID- 19840500
TI  - Effect of timing and method of post space preparation on sealing ability of
      remaining root filling material: in vitro microbiological study.
AB  - OBJECTIVE: To evaluate the effect of timing (immediate versus delayed) and
      technique of post space preparation on the ability of the residual root canal
      obturation to prevent coronal bacterial leakage. MATERIALS AND METHODS: Sixty-six
      single-rooted teeth were decoronated at the cementoenamel junction. The canals
      were prepared according to a step-back technique and were filled with
      thermoplasticized gutta-percha and AH Plus endodontic sealer (Dentsply De Trey).
      The root segments were randomly assigned to 8 groups. The positive controls (n =
      3) were instrumented but not obturated. The negative controls (n = 3) were
      instrumented, obturated and sealed with Cavit (3M ESPE). In the other 6 groups (n
      = 10 each), the post space was prepared either immediately after obturation or 7
      days later using LA Axxess burs (SybronEndo) (groups 1 and 2), heated pluggers
      (groups 3 and 4) or solvent delivered with a hand file (groups 5 and 6). The
      external surface of all roots was rendered waterproof with nail varnish. Custom
      made dual-chamber devices were used to evaluate leakage. The coronal third of the
      prepared root canal was kept in contact with artificial saliva contaminated with
      Enterococcus faecalis, and the root apex was submerged in tryptic soy agar
      medium. The root assemblies were stored at 37 degrees C and were monitored daily
      over a 90-day period. The occurrence of turbidity in the medium was deemed to
      indicate bacterial leakage, from which failure of the seal was inferred. RESULTS:
      Throughout the experimental period, there was no significant difference (p =
      0.094) among the preparation techniques, either immediate or delayed, in terms of
      bacterial leakage. CONCLUSIONS: Immediate and delayed post space preparation
      yielded similar outcomes in terms of the canal seal. Regardless of the timing and
      the technique of post space preparation, coronal bacterial leakage occurred over
      time.

PMID- 19840501
TI  - Probiotics for oral health: myth or reality?
AB  - For some decades now, bacteria known as probiotics have been added to various
      foods because of their beneficial effects for human health. The mechanism of
      action of probiotics is related to their ability to compete with pathogenic
      microorganisms for adhesion sites, to antagonize these pathogens or to modulate
      the host"s immune response. The potential application of probiotics for oral
      health has recently attracted the attention of several teams of researchers.
      Although only a few clinical studies have been conducted so far, the results to
      date suggest that probiotics could be useful in preventing and treating oral
      infections, including dental caries, periodontal disease and halitosis. This
      article summarizes the currently available data on the potential benefits of
      probiotics for oral health.

PMID- 19840502
TI  - Treatment options for teeth with open apices and apical periodontitis.
AB  - Three clinical cases involving teeth with open apices and apical periodontitis
      were treated using different protocols. The first case was managed with
      intracanal calcium hydroxide paste for 12 months before obturation with gutta
      percha and sealer. In the second case, an apical plug of mineral trioxide
      aggregate (MTA) was used before obturation with gutta-percha and sealer and
      treatment was completed during 2 appointments. In the third case, the tooth,
      which had a divergent root canal system, was completely obturated with MTA and
      treatment was also completed over 2 appointments. In all 3 cases, signs of bone
      healing were observed after treatment.

PMID- 19840503
TI  - Management of erythema multiforme associated with recurrent herpes infection: a
      case report.
AB  - Erythema multiforme is an acute mucocutaneous disorder, characterized by varying
      degrees of blistering and ulceration. We report a case of recurrent herpes
      associated erythema multiforme managed with prophylactic acyclovir. An 11-year
      old boy had lesions in the oral cavity and lips, which had been diagnosed as
      erythema multiforme minor. Four months later, the patient had desquamative
      gingivitis with erythematous lesions and necrotic areas in the skin. This episode
      was not related to drug intake, which suggests that the erythema multiforme was a
      result of herpetic infection. This hypothesis was supported by positive serology
      for herpes simplex virus. Five months later, the patient returned with new oral,
      skin and penis mucosal lesions. The diagnosis was confirmed as herpes simplex
      virus-associated erythema multiforme major. The episode was treated with
      acyclovir, and acyclovir was used prophylactically for 7 months to control the
      disease.

PMID- 19840504
TI  - C-reactive protein and malignancy: clinico-pathological association and
      therapeutic implication.
AB  - C-reactive protein (CRP) is a widely used systemic biomarker for diagnosing acute
      and chronic inflammation. During the past decade, serum CRP has been re
      emphasized by extending its clinical use to the prediction or diagnosis of
      cardiovascular diseases and other conditions, particularly malignancies. Serum
      CRP has also been found to be elevated in patients with many malignancies,
      implying a close linkage between inflammation and malignancy. Prospective studies
      have shown a higher risk of developing cancer in those with elevated serum CRP.
      CRP is produced by hepatocytes in response to inflammatory cytokines,
      particularly, interleukin-6 from the tumor microenvironment. Preoperative CRP
      levels are parallel to the progression or pathological stages of malignancies,
      including gastric cancer in patients in our series. Elevated CRP is a determinant
      predictor of lower survival rates in patients with several cancers, including
      esophageal, colorectal, hepatocellular, pancreatic, urinary bladder,
      renal,ovarian and cervical cancer, after surgical resection. The measurement of
      serum CRP is simple, cheap, and available in daily practice. It can serve as an
      additional prognostic predictor for survival and post-treatment monitoring in
      cancer patients. In the future, CRP-lowering agents might offer a promising
      benefit in the prevention and therapy of many different types of cancer.

PMID- 19840505
TI  - Strategies to enhance tendon graft--bone healing in anterior cruciate ligament
      reconstruction.
AB  - Tendon-bone incorporation of a tendon graft within the bone tunnel is a major
      concern when using a tendon graft for ligament reconstruction. Successful
      anterior cruciate ligament (ACL) reconstruction with a tendon graft requires
      solid healing of the tendon graft in the bone tunnels. Improvement of graft
      healing to bone is crucial to facilitate early and aggressive rehabilitation and
      a rapid return to full activity. Healing of a tendon graft in a bone tunnel
      requires bone ingrowth into the tendon. Indirect Sharpey fiber and direct
      fibrocartilage fixation of the tendon-bone interface provide different anchorage
      strength and interface properties. Based on normal ACL structure and the function
      of the insertion site, the ideal tendon graft would attach broadly to the surface
      of the bone at the femoral and tibial attachment sites by an intermediate zone of
      fibrocartilage. Theoretically, interface fibrocartilage formation as the
      translational structure from ligament to bone is physiological and functional.
      Our strategies to enhance tendon graft to bone healing, including the use of
      periosteum and a hydrogel containing periosteal progenitor cell and bone
      morphogenetic protein-2, are described. For clinical application, satisfactory
      results for ACL reconstruction can be achieved with the use of a periosteum
      enveloped hamstring tendon graft.

PMID- 19840506
TI  - New insights into polycistronic transcripts in eukaryotes.
AB  - In bacteria and archaea, many functionally related genes are organized into
      operons in order to be transcribed and translated simultaneously. Operons are
      rarely seen in eukaryotes except for the Trypanosome and nematode, in which they
      are first transcribed into polycistronic transcripts but then processed into
      individual mature mRNAs. Recently, several researchers described the findings of
      polycistronic transcripts also in insects, which revised the previous thoughts
      that polycistronic genes were absent or few in eukaryotes. Similar to prokaryotic
      operons, the encoded peptides or proteins are translated simultaneously from a
      single polycistronic mRNA, providing new insights into the evolution of
      polycistronic genes. More interestingly, one type of the newly identified
      polycistronic genes encodes biologically important peptides composed of as few as
      11 amino acids. These new findings will spur scientists to identify more small
      peptides in genome-solved organisms, and change the definition of coding
      sequences in genomic annotation.

PMID- 19840507
TI  - Nontuberculous mycobacterial lung disease in southern Taiwan.
AB  - BACKGROUND: The aim of this study was to assess the prevalence of the major
      nontuberculous mycobacterium (NTM) species and the outcome of their treatment in
      southern Taiwan (a high-prevalence area for mycobacterium tuberculosis [MTB]).
      METHODS: The study was a retrospective review of patients with NTM pulmonary
      disease at the Kaohsiung Chang Gung Memorial Hospital from 2004 to 2005. The
      variables recorded and analyzed included demographics, particularly age and
      gender; primary clinical presentations; chest radiographic findings; risk
      factors; medication and outcome of treatment. RESULTS: The study included 67
      patients with NTM pulmonary disease. The average age was 66.6+/-14.5 years and
      they were predominantly male (70.1%). Of these patients, 88.1% had pre-existing
      lung disease, with chronic obstructive pulmonary disease (61.2%) and TB (58.2%)
      as the main underlying lung diseases. Rapid-growth species (M. abscessus, 44.8%
      and M. fortuitum, 23.9%)were the most commonly isolated species. Of the forty
      patients that were treated and followed up for at least one year, 31 had a
      favorable outcome (mean duration of therapy, 8.46+/-2.96 months). CONCLUSIONS:
      The predominant species in southern Taiwan differ from those in other countries
      as well as in northern Taiwan, with rapid-growth species predominating in
      southern Taiwan.

PMID- 19840508
TI  - Abdominal tuberculosis: analysis of clinical features and outcome of adult
      patients in southern Taiwan.
AB  - BACKGROUND: Abdominal tuberculosis remains a serious health threat. This
      retrospective report aimed to analyze patients after the development of the
      tuberculosis control program by the Center of Disease Control (Taiwan) in January
      2000. The study was conducted at the Chang Gung Memorial Hospital-Kaohsiung,
      Taiwan. METHODS: Between January 2000 and December 2006, we evaluated 14 adult
      patients with abdominal tuberculosis by reviewing their clinical information,
      therapeutic methods and outcomes. Diagnosis of abdominal tuberculosis was made
      based on clinical features of abdominal infection with microbiological results
      from culture, acid-fast bacilli stain and polymerase chain reaction for
      Mycobacterium tuberculosis and/or histopathological confirmation from biopsy and
      ascites. RESULTS: Tuberculous peritonitis and intestinal tuberculosis were the
      most common type of infections followed by hepatic tuberculosis, and intra
      abdominal tuberculoma. 35.7% of these patients had the coexistence of extra
      abdominal infection. The most common clinical symptoms and signs were abdominal
      pain, abdominal distension, ascites and body weight loss. Fever was found in
      35.7% of patients and peritoneal signs were noted in 7.1%. Immunocompromised
      states and old age are relevant to adult abdominal tuberculosis. Overall,
      patients were diagnosed by bacteriology (35.7%), biopsy materials from laparotomy
      (42.8%), liver biopsy (14.3%), and biopsy materials from colonoscopy (7.2%).
      Patients were cured after taking antituberculous drugs for at least 6 months
      without relapse during regular follow-up for at least 2 years. However, three
      patients died of sepsis and decompensated liver cirrhosis during treatment.
      CONCLUSION: Extra vigilance in dealing with patients who present with unexplained
      abdominal conditions is the key to the diagnosis of abdominal tuberculosis. Early
      diagnosis, early antituberculous therapy and surgical treatment of the associated
      complications are essential for the survival of the patient.

PMID- 19840509
TI  - Transoral endoscopic CO2 laser microsurgery for early laryngeal cancers.
AB  - BACKGROUND: The impact of transoral endoscopic CO(2) laser microsurgery (TLM) for
      the treatment of Tis, T1, and T2 glottic cancer on local disease control,
      survival, and laryngeal preservation was investigated. METHODS: From October 1999
      to February 2008, 48 patients with a previously untreated early laryngeal
      malignant tumor who had been treated with TLM were enrolled in this study.
      Overall survival, primary and ultimate local control, and larynx preservation
      rates were calculated by the Kaplan-Meier method. The impact of anterior
      commissure involvement on the local control rate after primary TLM was performed
      was analyzed by the log-rank test. Functional results for postoperative voice
      were analyzed by patient telephone intelligibility. RESULTS: The overall 5-year
      survival rate was 97% (95% CI, 94%-100%), the primary 5-year local control rate
      was 72% (95% CI, 66%-92%), the local control rate exclusively for TLM was 85%
      (95% CI, 79%-99%), and the ultimate 5-year local control rate was 100%. Larynx
      preservation rate was 97% (95% CI, 94%-100%). Anterior commissure involvement in
      glottic cancer showed no statistically significant difference in primary local
      control rate (p = 0.9). Regarding the post-operative voice function, 47 patients
      (97.9%) were able to maintain adequate telephone intelligibility. CONCLUSION: In
      terms of long-term survival and locoregional control, TLM is an optimal primary
      treatment modality for early laryngeal cancer. With TLM treatment, involvement of
      the anterior commissure is not a poor prognostic indicator.

PMID- 19840510
TI  - Adjuvant androgen deprivation therapy loses its therapeutic benefit after
      premature termination: an experience of combined modality treatment on prostate
      cancer.
AB  - BACKGROUND: To investigate the effect of the premature termination of recommended
      androgen deprivation therapy (ADT) as an adjunct to radiotherapy. METHODS:
      Between December 2001 and March 2004, 92 patients with non-metastatic prostate
      cancer underwent primary, curative radiotherapy via an intensity-modulated
      technique. Four patients (5%) were treated with a dosage of 70.2 Gy, while 74
      (80%) and 14 patients (15%) were treated to 72 and 75.6 Gy. Thirty patients (33%)
      received pelvic irradiation to 45 Gy as a part of their treatment. Seventy-nine
      patients (86%) also received variable ADT, but only 35 patients (38%) followed a
      strict protocol when on ADT. Biochemical failure was defined as nadir plus 2
      ng/mL or if there was any clinical evidence of tumor recurrence. RESULTS: The
      median follow-up time was 37.5 months (20.4-57.8 months). The 3-year overall
      survival rate was 91.8%. The estimated 3 year recurrence-free survival rates were
      100%, 88.9%, and 69.7% for the low, intermediate, and high risk groups,
      respectively. High risk group patients receiving ADT of an inappropriate length
      was the only significant risk factor correlated to disease recurrence. The 3-year
      recurrence-free survival rate was extremely poor (28.6%) in high risk group
      patients who received adjuvant ADT for less than 2 years. This was significantly
      worse than patients with the same risk who received long-term ADT (88.1%) or no
      adjuvant ADT (76.4%, p < 0.001). CONCLUSIONS: Long-term adjuvant ADT after
      radiotherapy on high risk prostate cancer has no benefit if the duration is less
      than 2 years. Premature termination should be avoided.

PMID- 19840511
TI  - Retinoic acid syndrome in patients following the treatment of acute promyelocytic
      leukemia with all-trans retinoic acid.
AB  - BACKGROUND: Retinoic acid syndrome (RAS) is a potentially lethal complication
      during all-trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia
      (APL). The incidence and risk factors have been shown to vary in different
      series. In this study we want to establish the incidence of RAS in our hospital
      and try to elucidate factors that increase its risk. METHODS: We retrospectively
      analyzed 102 patients diagnosed with APL between August 1993 and December 2007 at
      Chang Gung Memorial Hospital, Taiwan. All patients received ATRA as an induction
      regimen with or without conventional chemotherapy. RESULTS: Eight of the 102
      patients (7.8%) experienced RAS which developed after a median of 9 days (range:
      2 to 23 days) of ATRA treatment. Respiratory distress and fever were the most
      common presentations, occurring in 7 of 8 patients (87.5%). Age, gender,
      morphological or molecular subtypes, an initial white blood cell (WBC) count of
      more than 10 x 10(9)/L and concurrent chemotherapy did not statistically
      attribute to the occurrence of RAS. One patient developed RAS manifesting with
      pulmonary hemorrhage but experienced a complete recovery after administration of
      high-dose dexamethasone. The RAS-related mortality was 12.5% (1 out of 8
      patients). CONCLUSION: The incidence of RAS in this study was similar to those of
      other series with ATRA and concurrent chemotherapy. Age, gender, morphological or
      molecular subtypes, an initial leukocyte count of more than 10 x 10(9)/L or the
      presence of concurrent chemotherapy is not significantly associated with the
      occurrence of the RAS.

PMID- 19840512
TI  - Clinical characteristics, precipitating stressors, and correlates of lethality
      among suicide attempters.
AB  - BACKGROUND: Given that suicide attempt is a major risk factor for suicide
      completion, this study investigated the clinical features, precipitating
      stressors, and the correlates of lethality in suicide attempters. METHODS: The
      sample comprised 357 people who had attempted suicide and had been sent to the
      emergency room in a general hospital from November 2002 to June 2005. Data
      collection was conducted by a consultant psychiatrist and social worker through
      interview. RESULTS: The proportion of females was much higher than that of males.
      Suicide attempts peaked at 20 to 29 years old in females, and 30 to 39 years old
      in males. The females reported significantly more family relationship problems
      than the males, while the males more commonly reported unemployment or economic
      problems. The most prevalent psychiatric diagnosis was affective disorders. The
      females had a higher rate of self-poisoning by medication than the males, while
      the males had a higher rate of self-poisoning by non-medicinal chemicals than the
      females. Those with high-lethality attempts were older than those with medium-
      and low-lethality attempts, and more were males. CONCLUSION: While females and
      young adults had higher rates of suicide attempts, males and the elderly were
      considered at higher risk for suicide completion.

PMID- 19840513
TI  - Low body mass index is an independent risk factor of locoregional recurrence in
      women with breast cancer undergoing breast conserving therapy.
AB  - BACKGROUND: To investigate the risk factors and prognosis for locoregional
      recurrence (LRR) after breast conserving treatment (BCT) in women with early
      breast cancer. METHODS: Women who had undergone BCT from 1998 to 2005 at Chang
      Gung Memorial Hospital were retrospectively reviewed. LRR was defined as the
      reappearance of invasive carcinoma in the treated breast and/or ipsilateral
      axillary lymph node (ALN). The appearance of carcinoma outside this area was
      defined as distant metastasis (DM). Patient characteristics, tumor
      characteristics, treatment modality, and follow-up clinical evaluations were
      analyzed. Survival was estimated by the Kaplan-Meier method and compared with the
      log-rank test. A multivariate model was built by the Cox regression method.
      RESULTS: This study included 858 patients, and the median follow up time was 36
      (range 6-193) months. Twenty seven patients developed LRR for a crude LRR rate of
      3.1%. The 5-year cumulative incidence of LRR was 5.0%. The mean age of patients
      at the primary operation was 45 (+/-9.8) years old. Their median body mass index
      (BMI) was 23 (range 16-40) kg/m(2). Univariate analysis of locoregional
      recurrence free survival (LRRFS) revealed that age < or =40 years, a low BMI (<
      or =24 kg/m(2)) and omission of postoperation radiotherapy were unfavorable
      factors. Low BMI and young age were independent prognostic factors for LRRFS in
      multivariate analysis. The five-year overall survival of patients with no
      recurrence, LRR and DM were 97.4%, 63.2% and 41.6%, respectively (p < 0.001).
      CONCLUSIONS: BCT in a young population can result in good locoregional control
      after careful preoperative evaluation. Women with a low BMI are at high risk of
      LRR.

PMID- 19840514
TI  - Reconstruction intramedullary nailing for ipsilateral femoral neck and shaft
      fractures: main factors determining prognosis.
AB  - BACKGROUND: Ipsilateral femoral neck and shaft fractures are rare, and currently
      available treatment methods each have their own benefits and limitations.
      Although reconstruction intramedullary nails have been considered to be effective
      alternative, clinical outcomes vary significantly in reports. METHODS: Thirty
      seven consecutive adult patients with 37 combined fractures were treated with
      reconstruction intramedullary nails. All combined fractures were caused by high
      energy injuries. Operations were performed as soon as possible after the
      patient's general condition was stabilized. Thirty combined fractures were
      treated within 24 hours, and the remaining seven were delayed for 3-13 days.
      Closed nailing was performed in all 37 subjects. Protected weight bearing was
      permitted as soon as possible postoperatively. RESULTS: Thirty-two patients were
      followed- up for an average of 23 months (range, 12-45 months). Neck fractures
      healed in 90.6% of patients, and shaft fractures healed in 78.1% of patients (p =
      0.11). The average union time was 16 weeks (range, 6-30 weeks) for the neck
      fractures and 35 weeks (range, 25-45 weeks) for the shaft fractures (p < 0.001).
      The average union time for the shaft were 34.2 weeks for the mildly-injured shaft
      group (Winquist I, II), and 42 weeks for the severely-injured shaft group
      (Winquist III, IV, segmental, p = 0.024). No neck or shaft malunion, femoral head
      osteonecrosis or wound infection occurred. CONCLUSIONS: The outcome of
      ipsilateral femoral neck and shaft fracture depends primarily on the result of
      the treatment of the femoral shaft fracture. Severe shaft injuries had poor
      results. The main factor may be that the shaft fracture in a combined fracture
      sustains very high energy, and local soft tissues are severely compromised. More
      meticulous management of the shaft fracture, neck reduction and post-op
      protective weight bearing, may improve the outcome and reduce complications.

PMID- 19840515
TI  - Percutaneous coronary intervention of a stenotic left anterior descending artery
      with anomalous origin of right coronary artery.
AB  - The anomalous origin of the right coronary artery (RCA) from the left anterior
      descending (LAD) artery is rare. We report a case of single coronary artery with
      proximal LAD severe stenosis. The RCA originated from an unreported course of
      conal branch from the LAD. This anomalous RCA also had collaterals from left
      circumflex. Coronary intervention was successfully carried out on a severe
      stenosis at the proximal LAD artery. To the best of our knowledge the scenario of
      anomalous course and intervention is still to be reported.

PMID- 19840516
TI  - Hepatic artery-duodenal fistula with gastrointestinal bleeding after liver
      transplantation.
AB  - Gastrointestinal bleeding caused by peptic ulcer or portal hypertension is a
      serious complication in liver transplant recipients. However, Gastrointestinal
      bleeding from hepatic artery origin after liver transplantation is rare. We
      report duodenal massive bleeding secondary to erosion of hepatic artery after
      liver transplantation in two patients. This was diagnosed by angiography and
      treated subsequently by surgical intervention with hepatic artery re-anastomosis.
      We could not salvage one of these patients who died of complications of graft
      failure. Therefore, early diagnosis and aggressive surgical intervention may be
      required in order to salvage both recipient and graft.

PMID- 19840517
TI  - Emergence of truly "individualized" therapy: the poly (adenosine diphosphate
      ribose) polymerase inhibitors.

PMID- 19840518
TI  - Alcohol and cancer incidence in women.

PMID- 19840519
TI  - New approaches to allogeneic hematopoietic stem cell transplantation in pediatric
      cancers.
AB  - About 30 years have passed since the first children underwent allogeneic
      hematopoietic stem cell transplantation (HSCT). Since then, there have been major
      improvements to identifying and expanding pools of donors, mobilizing and
      harvesting hematopoietic stem cells, conditioning therapies, transfusion
      medicine, antimicrobials, immunosuppression, and supportive care. These advances
      have broadened the application of HSCT to treat malignant and nonmalignant
      pediatric disorders. Currently, most children and young adults with cancer who
      undergo allogeneic HSCT are identified as having a malignancy that would be
      lethal if not for the biologic therapy that HSCT imparts, and remarkably, many of
      these patients can be cured. However, this cure still comes with costs, including
      infections, graft-versus-host disease, loss of potential, and psychosocial and
      financial stresses. New approaches are increasingly available that focus on
      immune modulation to reduce the burdens of HSCT while improving its therapeutic
      benefit.

PMID- 19840520
TI  - Neuroblastoma: biology and staging.
AB  - Neuroblastoma is the most common extracranial tumor of childhood, with about 650
      new cases each year in the United States. The clinical course of neuroblastoma is
      variable and depends on age at diagnosis, staging, histology, and specific
      genetic abnormalities, such as MYCN oncogene amplification or aberrations of
      chromosome 1p or 11q. A subset of tumors will undergo spontaneous regression,
      whereas others progress despite aggressive therapy. The varied clinical behavior
      reflects genetic heterogeneity, with many possible gene candidates identified in
      studies using comparative genetic hybridization arrays, RNA expression
      microarrays, and genome-wide association studies. Recent studies implicated the
      anaplastic lymphoma kinase gene in the tumorigenesis of many familial and some
      sporadic cases of neuroblastoma. The International Neuroblastoma Risk Group
      developed a new staging and risk classification, with recommendations for
      analysis of biological markers in neuroblastoma. This review discusses the
      biology of these tumors, current and new risk classification, and staging
      recommendations, with a brief outline of preferred treatment strategies.

PMID- 19840521
TI  - Acute promyelocytic leukemia in childhood.
AB  - Acute promyelocytic leukemia (APL) is a relatively rare form of acute myelogenous
      leukemia (AML). In the United States, APL in children constitutes only 5% to 10%
      of AML. Molecularly, the disease is characterized by a fusion protein,
      promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-alpha that results from
      a balanced reciprocal translocation between the PML gene on chromosome 15 and the
      RAR-alpha (RARA) gene on chromosome 17. A major advance in the field of APL
      treatment has been the use of all-trans-retinoic acid (ATRA). Advances in the
      treatment of APL have taken this form of AML from a disease with significant
      morbidity and mortality to one with an excellent outcome. This has resulted
      largely from the incorporation of ATRA into frontline regimens with chemotherapy.
      Anthracyclines remain a cornerstone of treatment at this point. Recent trials
      have shown a role for arsenic trioxide in both newly diagnosed and relapsed APL.

PMID- 19840522
TI  - Critical signaling pathways in bone sarcoma: candidates for therapeutic
      interventions.
AB  - Bone sarcomas cause disproportionate morbidity and mortality and desperately need
      new therapies as there has been little improvement in outcomes in 20 years.
      Identification of critical signaling pathways, including type 1 insulin-like
      growth factor receptor (IGF-1R) for Ewing sarcoma and possibly osteosarcoma, and
      the ERBB and the Wnt signaling pathways for osteosarcoma, have emerged as
      receptors mediating vital signals for bone sarcoma. Akt, mammalian target of
      rapamycin (mTOR), phosphoinositide 3-kinases, mitogen-activated protein kinase
      kinase, extracellular signal-regulated kinases, and Ras pathway play key roles in
      at least some tumors, and inhibition of mTOR in particular will likely lead to
      improved survival, although clinical trials are still underway. The Notch pathway
      and ezrin are essential for osteosarcoma metastasis, and Fas downregulation is
      necessary for survival of metastases in lungs. As little is known about
      chondrosarcoma signaling, more preclinical work is needed. By defining vital
      signaling pathways in bone sarcomas, small molecule inhibitors can be applied
      rationally, leading to longer survival and reducing morbidity and late effects
      from intensive chemotherapy.

PMID- 19840523
TI  - Contemporary considerations for neoadjuvant chemotherapy in primary ovarian
      cancer.
AB  - Surgery is essential for the successful treatment of patients with advanced
      ovarian cancer. Recent reports have raised questions about the best time to
      perform surgery with regard to administering chemotherapy. A prospective
      randomized clinical trial comparing neoadjuvant chemotherapy (ie, platinum-based
      chemotherapy before attempting cytoreductive surgery) and conventional treatment
      (ie, aggressive cytoreductive surgery followed by platinum-based chemotherapy)
      demonstrated no difference in progression-free and overall survival between the
      two treatment groups. The trial demonstrated the need for optimum surgical
      cytoreduction regardless of whether surgery is performed before or after
      neoadjuvant chemotherapy. As the postoperative morbidity and mortality was lower
      in the neoadjuvant treatment group, neoadjuvant chemotherapy should be considered
      a standard treatment for women with advanced ovarian cancer, particularly those
      unlikely to be surgically cytoreduced to no residual tumor. This article reviews
      contemporary considerations in the use of neoadjuvant chemotherapy in the
      treatment of primary ovarian cancer.

PMID- 19840524
TI  - Novel imaging modalities in gynecologic cancer.
AB  - Novel imaging modalities continue to emerge in medicine, and the advent of (18)F
      fluorodeoxyglucose-positron emission tomography (FDG-PET) has had a significant
      impact in the imaging of gynecologic malignancies. In cervical cancer, FDG-PET
      has excellent sensitivity and specificity for evaluation of initial disease, as
      well as assessment of post-treatment response and long-term surveillance. In
      ovarian cancer, FDG-PET can be a useful tool in assessing recurrent disease,
      especially in the setting of a rising cancer antigen-125 with a negative or
      equivocal CT or MRI. In uterine cancer, FDG-PET has been investigated in
      evaluating the extent of disease including nodal metastases, and in assessing
      recurrence. This article reviews novel imaging modalities in gynecologic cancer,
      with a special focus on FDG-PET/CT.

PMID- 19840525
TI  - The role of tobacco in cancer health disparities.
AB  - Although public health efforts have dramatically reduced the prevalence of
      smoking in the past several decades, smoking remains the leading cause of
      preventable morbidity and mortality in the United States. Moreover, tobacco use
      is becoming increasingly concentrated among individuals with the lowest levels of
      education, income, and occupational status. Profound racial/ethnic and
      socioeconomic status (SES) disparities exist for tobacco-related cancer incidence
      and mortality, and for access to and quality of cancer treatment. Furthermore,
      racial/ethnic minority and low SES smokers have greater difficulty quitting
      smoking, are less likely to use effective resources for quitting, and have
      limited access to evidence-based cessation treatments. Widespread implementation
      of population-based tobacco cessation approaches may have had the unintended
      effect of increasing tobacco-related cancer health disparities. It is crucial
      that vulnerable populations of smokers be provided with effective and accessible
      treatments for tobacco dependence, as this would have a profound impact on
      reducing tobacco-related cancer health disparities.

PMID- 19840526
TI  - Colorectal cancer screening.
AB  - Colorectal cancer (CRC) constitutes the second leading cause of death from cancer
      in the United States. Increased screening for CRC have been associated with a
      decreased incidence in the past two decades. Continued efforts are necessary to
      maintain this trend. Appropriate risk stratification of individuals and
      compliance with recommended screening strategies are important. Colonoscopy
      continues to play an important role in screening; however, several different
      screening options are available for average-risk individuals. This article
      reviews the current options open to physicians to adequately screen patients for
      CRC based on inherit risks.

PMID- 19840528
TI  - Commentary on the contents of this issue.

PMID- 19840527
TI  - Exercise and breast cancer prevention.
AB  - Epidemiologic research continues to confirm a strong inverse association between
      physical activity and breast cancer risk. New studies suggest that activity
      during adolescence is most important for premenopausal breast cancer. Long-term
      activity patterns are clearly important for postmenopausal breast cancer,
      although recent activity often highly correlates with long-term activity,
      accounting for its influence on risk. Whether physical activity has greater
      influence on estrogen receptor- or progesterone receptor-negative breast cancers
      or affects receptor-negative and receptor-positive tumors equally remains a
      question. Studies have established that lower sex hormone levels likely explain
      lower breast cancer risk in physically active women. Overall, the evidence
      regarding physical activity and breast cancer risk highlights the importance for
      young women to adopt a physically active lifestyle that is maintained throughout
      life and for medical practitioners to counsel patients and prescribe exercise for
      its critically important health benefits, which include reducing a woman's breast
      cancer risk.

PMID- 19840529
TI  - The effect of exenatide on lisinopril pharmacodynamics and pharmacokinetics in
      patients with hypertension.
AB  - OBJECTIVES: This study evaluated the potential effect of exenatide on the
      pharmacokinetics and pharmacodynamics of lisinopril in patients with mild-to
      moderate hypertension. METHODS: 22 patients with mild-to-moderate primary
      hypertension participated in a double-blind, randomized, placebo-controlled, 2
      period, 2-sequence crossover study. Patients on stable lisinopril therapy were
      randomly assigned to receive subcutaneous exenatide (10 microg b.i.d.) and
      placebo b.i.d. separated by at least 2 days washout period. The primary
      pharmacodynamic parameters were baseline-adjusted 24-hour mean systolic and
      diastolic blood pressure. Steady state plasma lisinopril concentration-time
      profiles were also assessed. RESULTS: Mean blood pressure changes were not
      significantly different between exenatide and placebo coadministered with
      lisinopril. The least squares mean differences (95% CI) between treatments were
      +1.38 mmHg (-1.41, 4.17) for diastolic and +1.38 mmHg (-1.95, 4.71) for systolic
      blood pressure. Exenatide delayed the time to attain maximum lisinopril
      concentration (tmax,ss) by 2 hours but did not significantly alter maximum
      lisinopril concentration (Cmax,ss) or area under the concentration-time profile
      (AUCtau,ss) over the 24-hour steady-state dosing interval. CONCLUSIONS: This
      study demonstrated that concurrent administration of exenatide did not produce
      clinically relevant changes in blood pressure and did not significantly alter
      lisinopril pharmacokinetics in patients with mild-to-moderate hypertension.

PMID- 19840530
TI  - A randomized study of the serum pharmacokinetics of lower thoracic extended
      release epidural morphine (DepoDur) after lidocaine-epinephrine test dose
      administration in patients undergoing upper abdominal surgery.
AB  - OBJECTIVE: The primary objective was to evaluate the serum pharmacokinetic
      profile of a single 15-mg dose of extended-release epidural morphine (EREM)
      administered at the lower thoracic epidural space alone or following a lidocaine
      epinephrine test dose in patients undergoing major upper abdominal surgery.
      MATERIALS AND METHODS: This randomized, open-label study recruited men and women
      > or = 18 years of age scheduled for major upper abdominal surgery. Patients were
      randomly assigned to 1 of 5 treatment groups and were administered a single 15-mg
      dose of EREM or EREM preceded by a 3 ml lidocaine (1.5%)/epinephrine (1 :
      200,000) test dose with or without a saline flush: EREM alone; test dose + flush
      + 3-minute wait + EREM; test dose + flush + 10-minute wait + EREM; test dose +
      flush + 15-minute wait + EREM; or test dose + 3-minute wait + EREM. EREM was
      administered at the lower thoracic epidural intervertebral space (T8 - T12)
      approximately 30 minutes before the surgical incision. Noncompartmental
      pharmacokinetic parameters were determined based on the serum concentration-time
      profiles of morphine and morphine metabolites. Effectiveness and safety were also
      assessed. RESULTS: The intent-to-treat and safety populations included 39
      patients; the pharmacokinetic population included 37 patients. Administration of
      EREM 3 minutes after a lidocaine-epinephrine test dose, with or without a flush,
      resulted in an increased mean maximum serum concentration of morphine (Cmax;
      flush, 30.2 +/- 8.5 ng/ml; no flush, 25.6 +/- 10.1 ng/ml; EREM alone, 11.5 +/-
      7.3 ng/ml) and a decreased median time to Cmax (tmax; flush, 0.2 h; no flush, 0.2
      h; EREM alone, 2.0 h) compared with administration of EREM alone, without
      affecting relative morphine bioavailability. Flushing the catheter and waiting 15
      minutes normalized the Cmax (11.4 +/- 6.4 ng/ml) but not the median tmax (0.5 h).
      There were no significant group differences in safety, tolerability, or analgesic
      effectiveness. CONCLUSIONS: The interaction between EREM and a lidocaine
      epinephrine test dose administered at T8 - T12 can be minimized by waiting 15
      minutes after test dose administration. The overall safety and effectiveness of
      15 mg EREM administered at the lower thoracic epidural intervertebral space in
      patients undergoing major upper abdominal surgery appears similar to that
      observed in previous studies assessing lumbar administration. ClinicalTrials.gov
      Identifier: NCT00728832.

PMID- 19840531
TI  - The impact of rational pharmacotherapy training reinforced via prescription audit
      on the prescribing skills of fifth-year medical students.
AB  - OBJECTIVE: The aim of the study was to demonstrate the impact of a rational
      pharmacotherapy (RPT) clerkship reinforced via prescription audit (PA) on the
      prescribing skills of fifth-year medical students trained by both pharmacologists
      and clinicians at Gazi University Medical School. METHODS: The RPT training
      lasted for five days. A total of 101 medical students were included in the study.
      The students were asked to prescribe for standardized patients with uncomplicated
      essential hypertension. PA was performed on the prescriptions on the first (PA1)
      and last (PA2) days of the clerkship to determine the influence of the clerkship
      on the prescribing habits. The students were also asked to comment on PA with a
      short questionnaire at the end of the clerkship. The difference between PA scores
      was analyzed using the Mann-Whitney-Rank-Sum-test. RESULTS: Scores for PA1 and
      PA2 and the feedback of the medical students were compared. A significant
      improvement in PA scores was observed by the end of the clerkship. The commonest
      drugs in the prescriptions in both PA1 and PA2 were angiotensin-converting enzyme
      (ACE) inhibitors. The feedback from the medical students revealed that PA
      improved their prescription skills and that the trainers helped them to reach the
      targets, helped them to gain self-confidence and they agreed that PA should be
      applied in clinical pharmacology courses. CONCLUSIONS: RPT training reinforced
      via PA guided by clinicians and pharmacologists is helpful in improving the
      prescribing skills of medical students. ACE inhibitors were the commonest group
      of drugs chosen by the medical students both before and after the clerkship.
      Prescription audit together with the clerkship caused a significant improvement
      in all parts of the prescription determined by prescription audit. The
      cooperation of pharmacologists and clinicians helped the clerkship to reach the
      targets.

PMID- 19840532
TI  - Population pharmacokinetics of albendazole in patients with neurocysticercosis.
AB  - OBJECTIVES: To determine a population pharmacokinetic model of the antihelmintic
      drug, albendazole, and identify the factors influencing the pharmacokinetic
      parameters in patients with neurocysticercosis. METHODS: A prospective study was
      performed in 90 patients receiving 30 mg/kg/day of albendazole for 8 days. Blood
      samples were collected at steady state. Plasma concentrations of albendazole
      sulfoxide, the main active metabolite of albendazole, were determined by HPLC.
      The population pharmacokinetics analysis was performed using non-linear mixed
      effect modeling (NONMEM). A one-compartment model with first order absorption and
      elimination was used. RESULTS: Body weight was included empirically on CL/F and
      V/F using an allometric relationship. Although none of the investigated
      covariates had a significant influence on the pharmacokinetic parameters of
      albendazole, the final model identified two subpopulations on the bioavailability
      parameter. One subpopulation comprising of 27% of the total population had a
      bioavailability of 28%, with the remaining subpopulation defined to have complete
      bioavailability. The CL/F and V/F for a standard 70 kg individual was determined
      to be 51.6 l/h and 4560 l, respectively. Interindividual variability in CL/F was
      32%; the residual unexplained variability was 32%. CONCLUSIONS: The considerable
      variability reported in albendazole pharmacokinetics and plasma concentrations is
      likely due to issues related to bioavailability. With one-fourth of the
      population absorbing as little as 30% of the drug relative to others, low drug
      exposures might be responsible for treatment failures. Therapeutic drug
      monitoring may be warranted to optimize the eradication of the infecting
      parasite.

PMID- 19840533
TI  - The effects of 1 month antihypertensive treatment with perindopril, bisoprolol or
      both on the ex vivo ability of monocytes to secrete inflammatory cytokines.
AB  - INTRODUCTION: Monocytes are key elements in pathogenesis of atherosclerosis and
      inflammation. The data regarding associations between antihypertensive treatment
      and monocytes' function are still lacking. The aim of this study was to evaluate
      the influence of antihypertensive drugs (bisoprolol, perindopril or both) in
      patients suffering from mild to moderate hypertension. PATIENTS AND METHODS: The
      study population consisted of 67 patients divided into 3 groups (2 consisted of
      patients with Grade I essential hypertension and one consisted of patients with
      Grade II essential hypertension). At baseline and 1 month after treatment we
      performed 24-h ambulatory noninvasive blood pressure monitoring and measured IL
      1beta, IL-6, IL-10, MCP-1 and TNF-alpha in a medium derived from LPS-stimulated
      monocytes' culture. RESULTS: Both monotherapies with bisoprolol or perindopril
      were equally effective in lowering blood pressure (reduction in mean 24-h
      systolic blood pressure 12.07 vs. 15.91 mmHg, p = 0.678). Antihypertensive
      treatment led to significant decrease in IL-1b, IL-6, MCP-1 and TNF-alpha
      concentration and significant rise in IL-10 level compared to the baseline levels
      and the decrease was associated with reduction in blood pressure. CONCLUSIONS:
      Bisoprolol and perindopril effectively reduced elevated blood pressure. As a
      result, an alteration in cytokine net was observed at the end of the study. These
      results support the concept of possible anti-inflammatory effects of
      antihypertensive drugs (e.g., perindopril and bisoprolol).

PMID- 19840534
TI  - Different time courses of nephrogenic systemic fibrosis: Is there a role for
      pharmacokinetic aspects in explaining a new clinical entity?
AB  - OBJECTIVE: To report 3 cases of nephrogenic systemic fibrosis (NSF) focussing on
      the time course of clinical symptoms after exposure to gadolinium based contrast
      agents (GBCA) and to discuss pharmacokinetic aspects of commercially available
      GBCA. PATIENTS' DETAILS: All 3 patients (2 men, 1 woman, aged 51 - 54 years)
      suffered from end-stage renal disease (ESRD) and were on long-term dialysis.
      Linear GBCA compounds were given to all patients and NSF symptoms started 6
      months, 1 and 4 years after the last GBCA exposure. In 2 patients, GBCA was
      administered after the occurrence of (unrecognized) NSF symptoms leading to
      worsening of clinical courses. 1 of the patients received multiple therapies
      (e.g. UV-A1 treatment, physical therapy) without significant improvement, 2
      patients died from cardiac complications shortly after the diagnosis of NSF.
      CONCLUSION: NSF may develop after a longer period of time than generally reported
      and GBCA administration may aggravate or accelerate chronic, subclinical NSF
      symptoms.

PMID- 19840535
TI  - Unexpected serum level of vancomycin after oral administration in a patient with
      severe colitis and renal insufficiency.
AB  - OBJECTIVE: To report a case in which the serum concentration of vancomycin (VCM)
      reached the supratherapeutic range following oral administration in a patient
      with severe pseudomembranous colitis and renal insufficiency. CASE SUMMARY: A 65
      year-old, 70 kg weighing man with severe acute pancreatitis and acute renal
      failure was subjected to continuous hemodiafiltration (CHDF). CHDF could only be
      performed intermittently because of the unstable circulation dynamic of this
      patient. After admission, intravenous VCM therapy was initiated. Thereafter, oral
      VCM administration was begun (0.5 g every 6 h). Despite the discontinuation of
      intravenous VCM after the first 2 days of oral VCM, the serum VCM concentration
      increased gradually to 49.8 mg/l over a period of 2 weeks from the initiation of
      oral administration (34.4 mg/l). Based on pharmacokinetic analysis, the
      bioavailability of VCM was estimated to over 33%. Autopsy findings indicated
      broadly distributed necrosis on the lamina propria of the mucosa throughout all
      parts of the intestine below the duodenum. DISCUSSION: This case indicates
      necessity of the careful monitoring after oral high-dose VCM administration in a
      patient with a broadly distributed necrosis and renal insufficiency. CONCLUSIONS:
      TDM should be considered according to renal function, the severity of enteritis
      and the total dosage of oral VCM administration.

PMID- 19840536
TI  - Modelling the dynamics of intramammary E. coli infections in dairy cows:
      understanding mechanisms that distinguish transient from persistent infections.
AB  - The majority of intramammary infections with Escherichia coli in dairy cows
      result in transient infections with duration of about 10 days or less, although
      more persistent infections (2 months or longer) have been identified. We apply a
      mathematical model to explore the role of an intracellular mammary epithelial
      cell reservoir in the dynamics of infection. We included biological knowledge of
      the bovine immune response and known characteristics of the bacterial population
      in both transient and persistent infections. The results indicate that varying
      the survival duration of the intracellular reservoir reproduces the data for both
      transient and persistent infections. Survival in an intracellular reservoir is
      the most likely mechanism that ensures persistence of E. coli infections in
      mammary glands. Knowledge of the pathogenesis of persistent infections is
      essential to develop preventive and treatment programmes for these important
      infections in dairy cows.

PMID- 19840540
TI  - Breaking boundaries in neural-immune interactions.
AB  - For the past 60 years, the central nervous system has been considered
      immunologically privileged. Yet results from diverse fields show clear and
      convincing evidence of bidirectional communication between the nervous and immune
      systems.

PMID- 19840537
TI  - Repeat tuberculin skin testing leads to desensitisation in naturally infected
      tuberculous cattle which is associated with elevated interleukin-10 and decreased
      interleukin-1 beta responses.
AB  - The principal surveillance tool used to control bovine tuberculosis in cattle is
      the removal of animals that provide a positive response to the tuberculin skin
      test. In this study we performed a longitudinal investigation of the
      immunological and diagnostic consequences of repeated short-interval skin-tests
      in cattle naturally infected with Mycobacterium bovis. Tuberculin skin-test
      positive cattle were subjected to up to four further intradermal comparative
      cervical skin-tests at approximately 60-day intervals. A significant progressive
      reduction in the strength of the skin-test was observed after successive tests.
      In contrast, the magnitude of interferon-gamma (IFN-gamma) responses was not
      influenced by repeat skin-testing either transiently around the time of each skin
      test or longitudinally following repeated tests. A significant boost in blood
      interleukin-10 (IL-10) production was observed within 3 days following each skin
      test although the magnitude of this boosted response returned to lower levels by
      day 10 post-test. The application of a novel multiplex assay to simultaneously
      measure seven cytokines and chemokines also identified that skin-testing resulted
      in a significant and progressive reduction in antigen specific interleukin-1beta
      (IL-1beta) whilst confirming stable IFN-gamma and elevated IL-10 responses in the
      blood. Therefore, we have demonstrated that in cattle naturally infected with M.
      bovis, repeat short-interval skin-testing can lead to a progressive reduction in
      skin-test responsiveness which has potential negative consequences for the
      detection of infected animals with marginal or inconclusive skin-test responses.
      The desensitising effect is associated with decreased IL-1beta and elevated IL-10
      responses, but importantly, does not influence antigen specific IFN-gamma
      responses.

PMID- 19840541
TI  - Neuroendocrine and immune influences on the CNS: it's a matter of sex.
AB  - Most neuropsychiatric diseases have a sex bias in their presentation, age of
      onset, or treatment response. Yet surprisingly, we have considered very little
      the contribution of the sexually dimorphic brain when thinking about disease
      etiology and the important influences of the neuroendocrine and immune systems in
      programming the CNS.

PMID- 19840542
TI  - Viral infection leading to brain dysfunction: more prevalent than appreciated?
AB  - Virus infections of the brain can lead to transient or permanent neurologic or
      psychiatric dysfunction. Some of the complexities in establishing the causal role
      of viruses in brain disease are explored here.

PMID- 19840543
TI  - Harnessing immune alterations in neurodegenerative diseases.
AB  - Immune dysfunction, a well-established feature of neuroinflammatory disease, is
      increasingly recognized in neurodegenerative conditions. Its role is emerging as
      an early and active participant in neuropathology. Inflammation could be
      modified, with disease-slowing effects, by targeted interventions; it is also
      readily detectable and could serve as a source of valuable biomarkers.

PMID- 19840544
TI  - The promise of epidemiologic studies: neuroimmune mechanisms in the etiologies of
      brain disorders.
AB  - We present our views on current and past epidemiological contributions to our
      understanding of neuroimmune mechanisms for neurodevelopmental disorders, such as
      schizophrenia. We also discuss future directions for epidemiological studies and
      ways in which newer cohorts are well positioned to address questions that were
      previously not feasible to explore.

PMID- 19840545
TI  - The neurology of the immune system: neural reflexes regulate immunity.
AB  - Parallel advances in neuroscience and immunology established the anatomical and
      cellular basis for bidirectional interactions between the nervous and immune
      systems. Like other physiological systems, the immune system--and the development
      of immunity--is modulated by neural reflexes. A prototypical example is the
      inflammatory reflex, comprised of an afferent arm that senses inflammation and an
      efferent arm, the cholinergic anti-inflammatory pathway, that inhibits innate
      immune responses. This mechanism is dependent on the alpha7 subunit of the
      nicotinic acetylcholine receptor, which inhibits NF-kappaB nuclear translocation
      and suppresses cytokine release by monocytes and macrophages. Here we summarize
      evidence showing that innate immunity is reflexive. Future advances will come
      from applying an integrative physiology approach that utilizes methods adapted
      from neuroscience and immunology.

PMID- 19840546
TI  - The stressed CNS: when glucocorticoids aggravate inflammation.
AB  - Glucocorticoids (GCs) are hormones released during the stress response that are
      well known for their immunosuppressive and anti-inflammatory properties; however,
      recent advances have uncovered situations wherein they have effects in the
      opposite direction. The CNS is a particularly interesting example, both because
      of its unique immune environment, and because GCs affect immune responses
      differently in different brain regions. In this minireview we discuss the
      contexts wherein GCs increase CNS inflammation and point out directions for
      future investigation.

PMID- 19840547
TI  - MHC class I: an unexpected role in neuronal plasticity.
AB  - For the nervous system to translate experience into memory and behavior, lasting
      structural change at synapses must occur. This requirement is clearly evident
      during critical periods of activity-dependent neural development, and
      accumulating evidence has established a surprising role for the major
      histocompatibility complex class I (MHCI) proteins in this process.

PMID- 19840548
TI  - Current challenges in glia-pain biology.
AB  - A remarkable series of findings over the last decade or so has demonstrated a
      previously unrecognized role for CNS glia in many aspects of neuronal functioning
      including pain processing. In addition to their recruitment to sites of CNS
      damage, these cells also appear to be capable of "action at a distance," playing
      functional roles in areas of CNS that are quite remote from the focus of injury
      or disease. The implication is that the nervous system is able to initiate
      signals that alter the function of these glial cells, and these cells in turn
      release factors that regulate neuronal function. This idea has taken root,
      resulting in an explosion of research interest, and here we look critically at
      what has been reported in order to assess where knowledge is missing or
      uncertain.

PMID- 19840549
TI  - Taking advantage of the systemic immune system to cure brain diseases.
AB  - The systemic immune system has the ability to modulate multiple brain functions,
      including autonomic responses, glial reactivity following neural injuries, and
      neuronal excitability. Immune stimuli also influence microglia subpopulations
      originating from blood progenitors, and neuroprotective and reparative capacities
      of blood-derived microglia were recently described in mouse models of spinal cord
      injury and brain disorders. Furthermore, reparative roles for various immune
      subsets have been recognized, such as in inducing myelin repair. Nonetheless,
      uncontrolled and excessive activation of immune responses can be detrimental. The
      development of strategies to stimulate the systemic immune system safely to
      protect or repair brain disorders remains a major challenge ahead, but important
      inroads have been made. We discuss here some of the mechanisms underlying the
      neuroprotective and reparative effects of the systemic immune system and the most
      promising immunotherapies tested in mouse models of injuries and diseases, such
      as Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis.

PMID- 19840550
TI  - Cytokines and CNS development.
AB  - Cytokines are pleotrophic proteins that coordinate the host response to infection
      as well as mediate normal, ongoing signaling between cells of nonimmune tissues,
      including the nervous system. As a consequence of this dual role, cytokines
      induced in response to maternal infection or prenatal hypoxia can profoundly
      impact fetal neurodevelopment. The neurodevelopmental roles of individual
      cytokine signaling pathways are being elucidated through gain- and loss-of
      function studies in cell culture and model organisms. We review this work with a
      particular emphasis on studies where cytokines, their receptors, or components of
      their signaling pathways have been altered in vivo. The extensive and diverse
      requirements for properly regulated cytokine signaling during normal nervous
      system development revealed by these studies sets the foundation for ongoing and
      future work aimed at understanding how cytokines induced normally and
      pathologically during critical stages of fetal development alter nervous system
      function and behavior later in life.

PMID- 19840552
TI  - Immune proteins in brain development and synaptic plasticity.
AB  - Many proteins first identified in the immune system are also expressed in the
      developing and adult nervous system. Unexpectedly, recent studies reveal that a
      number of these proteins, in addition to their immunological roles, are essential
      for the establishment, function, and modification of synaptic connections. These
      include proinflammatory cytokines (e.g., TNFalpha, IL-6), proteins of the innate
      immune system (e.g., complement C1q and C3, pentraxins, Dscam), members of the
      major histocompatibility complex class I (MHCI) family, and MHCI-binding
      immunoreceptors and their components (e.g., PIRB, Ly49, DAP12, CD3zeta).
      Understanding how these proteins function in neurons will clarify the molecular
      basis of fundamental events in brain development and plasticity and may add a new
      dimension to our understanding of neural-immune interactions in health and
      disease.

PMID- 19840551
TI  - Immune influence on adult neural stem cell regulation and function.
AB  - Neural stem cells (NSCs) lie at the heart of central nervous system development
      and repair, and deficiency or dysregulation of NSCs or their progeny can have
      significant consequences at any stage of life. Immune signaling is emerging as
      one of the influential variables that define resident NSC behavior. Perturbations
      in local immune signaling accompany virtually every injury or disease state, and
      signaling cascades that mediate immune activation, resolution, or chronic
      persistence influence resident stem and progenitor cells. Some aspects of immune
      signaling are beneficial, promoting intrinsic plasticity and cell replacement,
      while others appear to inhibit the very type of regenerative response that might
      restore or replace neural networks lost in injury or disease. Here we review
      known and speculative roles that immune signaling plays in the postnatal and
      adult brain, focusing on how environments encountered in disease or injury may
      influence the activity and fate of endogenous or transplanted NSCs.

PMID- 19840554
TI  - Innate and adaptive autoimmunity directed to the central nervous system.
AB  - The immune system has two major components, an innate arm and an adaptive arm.
      Certain autoimmune diseases of the brain represent examples of disorders where
      one of these constituents plays a major role. Some rare autoimmune diseases
      involve activation of the innate arm and include chronic infantile neurologic,
      cutaneous, articular (CINCA) syndrome. In contrast, adaptive immunity is
      prominent in multiple sclerosis, neuromyelitis optica, and the paraneoplastic
      syndromes where highly specific T cell responses and antibodies mediate these
      diseases. Studies of autoimmune brain disorders have aided in the elucidation of
      distinct neuronal roles played by key molecules already well known to
      immunologists (e.g., complement and components of the major histocompatibility
      complex). In parallel, molecules known to neurobiology and sensory physiology,
      including toll-like receptors, gamma amino butyric acid and the lens protein
      alpha B crystallin, have intriguing and distinct functions in the immune system,
      where they modulate autoimmunity directed to the brain.

PMID- 19840553
TI  - Immune activation in brain aging and neurodegeneration: too much or too little?
AB  - Until recently, the brain was studied almost exclusively by neuroscientists and
      the immune system by immunologists, fuelling the notion that these systems
      represented two isolated entities. However, as more data suggest an important
      role of the immune system in regulating the progression of brain aging and
      neurodegenerative disease, it has become clear that the crosstalk between these
      systems can no longer be ignored and a new interdisciplinary approach is
      necessary. A central question that emerges is whether immune and inflammatory
      pathways become hyperactivated with age and promote degeneration or whether
      insufficient immune responses, which fail to cope with age-related stress, may
      contribute to disease. We try to explore here the consequences of gain versus
      loss of function with an emphasis on microglia as sensors and effectors of immune
      function in the brain, and we discuss the potential role of the peripheral
      environment in neurodegenerative diseases.

PMID- 19840556
TI  - Usefulness of age and gender in the early triage of patients with acute chest
      pain having cardiac computed tomographic angiography.
AB  - To identify the age- and gender-specific subpopulations of patients with acute
      chest pain in whom coronary computed tomographic angiography (CTA) will yield the
      greatest diagnostic benefit. Subjects with acute chest pain and an inconclusive
      initial evaluation (nondiagnostic electrocardiograhic findings, negative cardiac
      biomarkers) underwent contrast-enhanced 64-slice coronary CTA as a part of an
      observational cohort study. Independent investigators determined the presence of
      significant coronary stenosis (>50% luminal narrowing) and the occurrence of
      acute coronary syndrome (ACS) during the index hospitalization. We determined the
      diagnostic accuracy and effect on pretest probability of ACS using Bayes' theorem
      by age and gender. Of 368 patients (age 52.7 +/- 12 years, 61% men), 8% had ACS.
      The presence of significant coronary stenosis on CTA and the occurrence of ACS
      increased with age for both men and women (p <0.001). Cardiac CTA was highly
      sensitive and specific in women <65 years of age (sensitivity 100% and
      specificity >87%) and men <55 years of age (sensitivity 100% for men <45 years
      and 80% for men 45 to 54 years old; specificity >88.2%). Moreover, in these
      patients, coronary CTA led to restratification from low to high risk (for
      positive findings on CTA) or from low to very low risk (for negative findings on
      CTA). In contrast, a negative result on CTA did not result in restratification to
      a low-risk category in women >65 years and men >55 years old. In conclusion, the
      present analysis provides initial evidence that men <55 years and women <65 years
      might benefit more from cardiac CTA than older patients. Thus, age and gender
      might serve as simple criteria to appropriately select patients who would derive
      the greatest diagnostic benefit from coronary CTA in the setting of acute chest
      pain.

PMID- 19840557
TI  - Patient characteristics associated with the choice of triple antithrombotic
      therapy in acute coronary syndromes.
AB  - Evidence regarding the use of dual antiplatelet therapy and oral anticoagulation
      (i.e., triple therapy) in acute coronary syndromes (ACS) is limited. We evaluated
      the characteristics associated with the choice of triple therapy in ACS. Using
      the Get With The Guidelines (GWTG) Coronary Artery Disease national registry, we
      studied patients with ACS at 361 sites in the United States from 2004 to 2007.
      Both univariate analysis and multivariate logistic regression analysis were used
      to assess the factors associated using triple therapy on discharge. The
      Generalized Estimating Equation method was used to account for within-hospital
      clustering in modeling. A total of 86,304 patients presented with ACS during the
      study period. At discharge, 3,933 patients (4.6%) were prescribed triple therapy,
      60,716 patients (70.4%) received dual antiplatelet therapy, 2,348 patients (2.7%)
      received single antiplatelet therapy plus oral anticoagulation, 19,065 patients
      (22.1%) received antiplatelet monotherapy, and 242 patients (0.3%) received oral
      anticoagulation alone. Patients with a history of atrial fibrillation (odds ratio
      7.01, 95% confidence interval 6.06 to 8.12; p <0.001), documented new-onset
      atrial fibrillation (odds ratio 3.76, 95% confidence interval 2.87 to 4.93; p
      <0.001), or history of atrial flutter (odds ratio 3.38, 95% confidence interval
      2.15 to 5.32; p <0.001) were more frequently discharged with triple therapy. In
      conclusion, for patients with ACS, atrial fibrillation and atrial flutter were
      most strongly associated with the use of triple therapy; however, this therapy
      was used less often than dual or single antiplatelet therapy.

PMID- 19840558
TI  - The chemokine network in relation to infarct size and left ventricular remodeling
      following acute myocardial infarction.
AB  - Increased circulating chemokines have been reported during acute myocardial
      infarction and might give prognostic information about future ischemic events.
      However, data on the chemokine network in relation to infarct size and measures
      of left ventricular remodeling after successful percutaneous coronary
      intervention (PCI) are lacking. A total of 42 patients with first-time ST-segment
      elevation acute myocardial infarction with a single occluded vessel were
      recruited, and cardiac magnetic resonance was used for serial assessment (2, 7,
      and 60 days) of infarct size and left ventricular remodeling. The chemokines were
      analyzed before and after PCI. After PCI, high levels of CCL4, CXCL16, CXCL10,
      and, in particular, CXCL8 within the first week after PCI correlated positively
      with the degree of myocardial damage, as reflected by correlations with the
      maximum troponin T levels and infarct size after 2 months, as assessed by cardiac
      magnetic resonance, and with impaired myocardial function after 2 months as
      assessed by cardiac magnetic resonance and neurohormonal methods. In contrast,
      the plasma levels of CCL3 and CXCL7 during the first week correlated negatively
      with myocardial dysfunction after 2 months. In conclusion, our findings suggest a
      role for chemokines in both adaptive and maladaptive responses after myocardial
      infarction and might support a role for CCL4, CXCL16, CXCL10, and, in particular,
      CXCL8 in postmyocardial infarction reperfusion and remodeling.

PMID- 19840555
TI  - A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus
      infection.
AB  - The use of antiretroviral therapy has reduced mortality and increased the quality
      of life of HIV-1-infected people, particularly in more developed countries where
      access to treatment is more widespread. However, morbidities continue, which
      include HIV-1-associated neurocognitive disorders (HAND). Subtle cognitive
      abnormalities and low-level viral replication underlie disease. The balance
      between robust antiviral adaptive immunity, neuronal homeostatic mechanisms, and
      neuroprotective factors on one hand and toxicities afforded by dysregulated
      immune activities on the other govern disease. New insights into the
      pathobiological processes for neuroimmune-linked disease and ways to modulate
      such activities for therapeutic gain are discussed. Better understanding of the
      complexities of immune regulation during HAND can improve diagnosis and disease
      outcomes but is also relevant for the pathogenesis of a broad range of
      neurodegenerative disorders.

PMID- 19840559
TI  - Comparison between myocardial contrast echocardiography and (99m)technetium
      sestamibi single photon emission computed tomography determined myocardial
      viability in predicting hard cardiac events following acute myocardial
      infarction.
AB  - The extent of residual myocardial viability (MV) after acute myocardial
      infarction (AMI) is an important determinant of the outcome. Single photon
      emission computed tomography (SPECT) is widely used to assess MV after an AMI.
      However, myocardial contrast echocardiography (MCE), a relatively new technique
      for the assessment of MV, has better spatial and temporal resolution than SPECT.
      The present study evaluated whether MV determined by MCE is comparable to that
      determined using SPECT for the prediction of hard cardiac events after an AMI.
      Accordingly, 99 patients who had undergone simultaneous rest low-power MCE and
      nitrate-enhanced SPECT 7 days after an AMI were followed up for cardiac death and
      AMIs. Both MCE perfusion (1 = normal; 2 = reduced; and 3 = absent) and SPECT
      tracer uptake (0 = normal; 1 = mildly reduced; 2 = moderately reduced; 3 =
      severely reduced; and 4 = absent) were scored on a 16-segment left ventricular
      model. The contrast perfusion index and SPECT perfusion index were calculated by
      adding the respective scores in the 16 segments and dividing by 16. The contrast
      perfusion index and SPECT perfusion index were used as a measure of the residual
      MV on MCE and SPECT, respectively. Of the 99 patients recruited, 95 were
      available for the follow-up examination (follow-up 46 +/- 16 months). A total of
      15 events (16%) occurred (8 cardiac deaths and 7 AMIs). Of the clinical,
      biochemical, echocardiographic, and SPECT markers of prognosis, the only
      independent predictors of cardiac death and cardiac death or AMI were age and MV
      as determined by MCE (p = 0.01 and p = 0.002, respectively). In conclusion, MV
      determined by MCE at rest was superior to nitrate-enhanced SPECT for the
      prediction of hard cardiac events after AMI.

PMID- 19840560
TI  - Prevalence of unresponsiveness to aspirin and/or clopidogrel in patients with
      stable coronary heart disease.
AB  - This study sought to assess whether inadequate platelet responses to aspirin and
      clopidogrel are distinct phenomena caused by different mechanisms or different
      facets of the same phenomenon (i.e., general platelet hyperactivity). A total of
      85 patients with stable coronary artery disease who were taking aspirin and
      clopidogrel daily for > or =3 months were enrolled in the present study. Platelet
      aggregation was measured by light transmission aggregometry (LTA) stimulated with
      1.6 mM of arachidonic acid and 5, 10 and 20 microM of adenosine diphosphate, and
      by the VerifyNow Aspirin and VerifyNow P2Y12 point-of-care assays. An inadequate
      platelet response was defined as aggregation greater than or equal to the mean +
      2 SDs. The prevalence of an inadequate platelet response varied greatly among the
      assays. For aspirin, the prevalence was 2.4% using arachidonic acid-induced LTA
      and 5.9% using the VerifyNow Aspirin assay. For clopidogrel, the prevalence
      varied from 1.2% to 3.9% using adenosine diphosphate-induced LTA and was 2.4%
      using the VerifyNow P2Y12 assay. The point-of-care assays did not select the same
      patients as LTA. No subject was unresponsive to both aspirin and clopidogrel,
      regardless of the assay used, suggesting that separate mechanisms govern platelet
      unresponsiveness to aspirin and clopidogrel. In conclusion, an inadequate
      platelet response to either aspirin or clopidogrel is rare, and the definition is
      dependent on the platelet function assay used. Because no subject was found to be
      unresponsive to both agents, the unresponsiveness is suspected to occur through
      distinct mechanisms of platelet activation.

PMID- 19840561
TI  - Screening for depression and suicidality in patients with cardiovascular
      illnesses.
AB  - The American Heart Association (AHA) and the American Psychiatric Association
      jointly recommend screening for depression in cardiology clinics. This includes
      screening for suicidality. It is not known how frequently patients disclose
      suicidal thinking (ideation) in this setting, and what proportion of those will
      turn out to have suicidal intent. Patients were screened for depression using a
      protocol identical to the one endorsed by the AHA in a cardiology community
      clinic in Elmhurst (Queens, New York). Depression was assessed using the Patient
      Health Questionnaire. Reports of suicidal ideation were immediately evaluated by
      a mental health professional. We determined the degree to which suicidal ideation
      was identified, the proportion of patients with suicidal intent of those
      reporting suicidal ideation, and the relation between depression and suicidal
      ideation in this setting. One thousand three patients were screened; 886 had
      complete Patient Health Questionnaire data. Of those, 12% (109 patients)
      expressed suicidal ideation. Four of those were hospitalized for suicidal intent
      (0.45% of all screened patients). Suicidal ideation and depression were
      correlated (point biserial correlation coefficient 0.478). In conclusion,
      suicidal ideation can and will be identified using the AHA depression screening
      recommendations, but only a very small fraction (0.45%) of screened patients will
      turn out to have suicidal intent. Discovery and stabilization of suicidal
      patients is an important benefit of the screening, but the fact that >12% of all
      screened patients will need to be immediately evaluated for suicidal intent has
      important implications for resource allocation to screening programs.

PMID- 19840562
TI  - Association of door-to-balloon time and mortality in patients > or =65 years with
      ST-elevation myocardial infarction undergoing primary percutaneous coronary
      intervention.
AB  - Current guidelines recommend patients with ST-elevation myocardial infarction
      receive primary percutaneous coronary intervention (PCI) within 90 minutes of
      admission, although there are conflicting data regarding the relation between
      time to treatment and mortality in these patients. We used logistic regression
      analyses employing a fractional polynomial model to evaluate the association
      between door-to-balloon time and 1-year mortality in patients with ST-elevation
      myocardial infarction > or =65 years old undergoing primary PCI from 1994 to 1996
      (n = 1,932). Median door-to-balloon time was 128 minutes (interquartile range 92
      to 178, 24.2% treated within 90 minutes). Overall 1-year mortality was 21.1%.
      Longer door-to-balloon times were associated with higher 1-year mortality in a
      continuous, nonlinear fashion (30 minutes 10.9%, 60 minutes 13.6%, 90 minutes
      16.5%, 120 minutes 19.5%, 150 minutes 22.5%, 180 minutes 25.3%, 210 minutes
      27.9%). The nature of the association between door-to-balloon time and 1-year
      mortality was best modeled by a second-degree fractional polynomial (p <0.001).
      Findings were similar after multivariable adjustment as any increase in door-to
      balloon time was associated with successive increases in patients' 1-year
      mortality (30 minutes 8.8%, 60 minutes 12.9%, 90 minutes 16.6%, 120 minutes
      19.9%, 150 minutes 22.9%, 180 minutes 25.5%, 210 minutes 27.7%). In conclusion,
      any delay in primary PCI is associated with increased 1-year mortality,
      suggesting efforts should focus on decreasing time to treatment as much as
      possible, even among those centers currently providing primary PCI within 90
      minutes.

PMID- 19840563
TI  - Effect of coronary collaterals on microvascular obstruction as assessed by
      magnetic resonance imaging in patients with acute ST-elevation myocardial
      infarction treated by primary coronary intervention.
AB  - The aim of this study was to determine whether angiographically visible
      collaterals before reperfusion are associated with beneficial effects on infarct
      size, microvascular obstruction, and left ventricular function as measured by
      magnetic resonance imaging (MRI) in patients with ST-elevation myocardial
      infarction (STEMI) undergoing percutaneous coronary intervention (PCI). We
      examined 235 patients with STEMI and symptoms <12 hours. All patients had
      Thrombolysis In Myocardial Infarction grade < or =1 flow before PCI. Collateral
      flow was graded according to Rentrop classification. Patients were divided in 2
      groups; group A had absent or weak collateral flow and group B had significant
      flow. In 166 patients there was absent or weak collateral flow, whereas 69 had
      significant flow. Extent of microvascular obstruction was significantly smaller
      in group B at early MRI (3.3% vs 2.1% of left ventricle, p = 0.009). Infarct size
      measured by peak creatine kinase release showed smaller infarcts in group B (p =
      0.02), whereas MRI infarct size showed a weak trend (p = 0.20). At 6 months, a
      strong trend toward a lower rate of death or nonfatal reinfarction could be seen
      in group B (4.5% vs 12.2%, p = 0.07). In conclusion, well-developed collaterals
      before reperfusion by PCI in patients with STEMI are associated with a protective
      effect on coronary microcirculation.

PMID- 19840564
TI  - Relation of troponin I levels following nonemergent percutaneous coronary
      intervention to short- and long-term outcomes.
AB  - Increases of creatine kinase (CK) and CK-MB cardiac enzymes after nonemergent
      percutaneous coronary intervention (PCI) have been associated with an increased
      risk of cardiovascular events during follow-up. However, there are limited data
      about the incidence and prognostic significance of an isolated increase of
      cardiac troponin I (cTnI) without an increase in CK-MB after PCI. The aim of this
      study was to evaluate the impact of an isolated cTnI increase on long-term
      survival in patients undergoing nonemergent PCI with normal CK-MB levels after
      PCI. Using the 2004/2005 Cornell Angioplasty Registry, we evaluated the clinical
      outcomes in 1,601 patients (undergoing elective or urgent PCI) with normal
      preprocedure cTnI and CK-MB and normal CK-MB levels after the procedure. Patients
      were divided into 2 groups based on the presence of cTnI increase after PCI. The
      mean follow-up period was 24.6 +/- 7.6 months. An increase in cTnI was observed
      in 831 patients (51.9%). Drug-eluting stents were used in 87% of patients and
      glycoprotein IIb/IIIa inhibitors were administered in 48% of patients. Incidence
      of in-hospital major adverse cardiovascular events was low, 0.1% versus 0% (p =
      1.000), in patients with versus without cTnI increases, respectively. By 2 years
      of follow-up, Kaplan-Meier survival rates were 94.1% versus 96.4% (log-rank p =
      0.020) in those with versus without cTnI increases, respectively. By multivariate
      Cox regression analysis, an increase in cTnI after PCI (hazard ratio 1.62, 95%
      confidence interval 1.01 to 2.59, p = 0.047) was an independent predictor of
      increased long-term mortality. In conclusion, an isolated increase in cTnI after
      nonemergent PCI is common, not associated with more frequent adverse in-hospital
      outcomes compared to patients with normal cTnI, and provides long-term prognostic
      information regarding mortality.

PMID- 19840565
TI  - Serial intravascular ultrasound analysis of bifurcation lesions treated using the
      novel self-expanding sideguard side branch stent.
AB  - We used intravascular ultrasound (IVUS) to assess the efficacy of the Cappella
      Sideguard stent system for treating coronary bifurcation lesions. Treatment of
      bifurcation lesions is associated with restenosis at the side branch (SB) ostium,
      presumably due to inadequate coverage or stent-vessel wall malapposition. To
      address these limitations, the Sideguard stent was developed. It includes a
      balloon-deployed, self-expanding, thin-strut, low-stress, nitinol bare metal
      stent with anatomic funnel-shaped flaring at the SB ostium. Of 25 patients
      enrolled in the Sideguard I First-In-Man study, complete serial (after
      intervention and 6-month follow-up) IVUS images were available in 11 patients.
      All patients were treated with (1) predilation of the SB, (2) Sideguard stenting
      in the SB, (3) Cypher stenting in the main vessel, and (4) kissing balloon
      inflations. The Sideguard stent area at the SB carina increased from 3.9 +/- 1.2
      to 4.6 +/- 1.1 mm(2) (p = 0.04), resulting in no change in lumen area (3.9 +/-
      1.3 vs 4.0 +/- 1.3 mm(2), p = 0.77) despite an intimal hyperplasia (IH) area of
      0.6 +/- 0.7 mm(2). Six patients had minimal IH; the increase in stent area
      translated into an increase in lumen area of 0.4 +/- 0.6 mm(2); 5 patients had
      relatively more IH (1.3 +/- 0.4 mm(2)), but the increase in stent area of 1.3 +/-
      0.3 mm(2) compensated for the IH, resulting in no lumen decrease. In contrast,
      the main vessel stent area at the carina did not change (5.9 +/- 1.1 vs 6.0 +/-
      1.2 mm(2), p = 0.35). In conclusion, serial IVUS analyses of the self-expanding
      bare metal Sideguard stent indicate preserved SB ostial lumen dimensions at
      follow-up due to additional increases in stent area that more than compensated
      for IH.

PMID- 19840566
TI  - Comparison of bivalirudin monotherapy versus unfractionated heparin plus
      tirofiban in patients with diabetes mellitus undergoing elective percutaneous
      coronary intervention.
AB  - Bivalirudin demonstrated similar efficacy but resulted in a lower rate of
      bleeding compared to unfractionated heparin (UFH) plus platelet glycoprotein
      IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention. It
      has not been clearly evaluated whether this can also be applied to patients with
      diabetes mellitus. A total of 335 consecutive patients with diabetes mellitus
      referred for elective percutaneous coronary intervention were randomized in the
      Novel Approaches for Preventing or Limiting EventS (NAPLES) trial to receive
      bivalirudin monotherapy or UFH plus routine tirofiban. The primary composite end
      point (30-day composite incidence of death, urgent repeat revascularization,
      myocardial infarction, and all bleeding) was lower in the bivalirudin group than
      in the UFH plus tirofiban group (18.0% vs 31.5%, odds ratio 0.47, 95% confidence
      interval 0.28 to 0.79, p = 0.004). No death, urgent revascularization, or Q-wave
      myocardial infarction occurred. The rate of non-Q-wave myocardial infarction was
      similar in the 2 groups (10.2% in the bivalirudin group vs 12.5% in the UFH plus
      tirofiban group, p = 0.606). In contrast, fewer patients in the bivalirudin group
      experienced bleeding (8.4% vs 20.8%, odds ratio 0.34, 95% confidence interval
      0.18 to 0.67, p = 0.002). This difference was mainly ascribed to the lower rate
      of minor bleeding (7.8% in the bivalirudin group vs 18.5% in the UFH plus
      tirofiban group, odds ratio 0.37, 95% confidence interval 0.19 to 0.74, p =
      0.005), although the rate of major bleeding in the 2 groups was comparable (0.6%
      vs 2.4%, respectively; p = 0.371). In conclusion, in patients with diabetes
      mellitus undergoing elective percutaneous coronary intervention, the strategy of
      bivalirudin monotherapy compared to UFH plus routine tirofiban is safe and
      feasible and associated with a significant reduction of in-hospital bleeding.

PMID- 19840567
TI  - Timing of noncardiac surgery after coronary artery stenting with bare metal or
      drug-eluting stents.
AB  - The current guidelines have recommended postponing noncardiac surgery (NCS) for >
      or =6 weeks after bare metal stent (BMS) placement and for > or =1 year after
      drug-eluting stent (DES) placement. However, much debate has ensued about these
      intervals. The aim of the present study was to assess the influence of different
      intervals between stenting and NCS and the use of dual antiplatelet therapy on
      the occurrence of perioperative major adverse cardiac events (MACEs). We
      identified 550 patients (376 with a DES and 174 with a BMS) by cross-matching the
      Erasmus Medical Center percutaneous coronary intervention (PCI) database with the
      NCS database. The following intervals between PCI-BMS (<30 days, <3 months, and
      >3 months) or PCI-DES (<30 days, <3 months, 3 to 6 months, 6 to 12 months, and
      >12 months) and NCS were studied. MACEs included death, myocardial infarction,
      and repeated revascularization. In the PCI-BMS group, the rate of MACEs during
      the intervals of <30 days, 30 days to 3 months, and >3 months was 50%, 14%, and
      4%, respectively (overall p <0.001). In the PCI-DES group, the rate of MACE
      changed significantly with the interval after PCI (35%, 13%, 15%, 6%, and 9% for
      patients undergoing NCS <30 days, 30 days to 3 months, 3 to 6 months, 6 to 12
      months, and >12 months, respectively, overall p <0.001). Of the patients who
      experienced a MACE, 45% and 55% were receiving single and dual antiplatelet
      therapy at NCS, respectively (p = 0.92). The risk of severe bleeding in patients
      with single and dual therapy at NCS was 4% and 21%, respectively (p <0.001). In
      conclusion, we found an inverse relation between the interval from PCI to NCS and
      perioperative MACEs. Continuation of dual antiplatelet therapy until NCS did not
      provide complete protection against MACEs.

PMID- 19840568
TI  - Impact of final activated clotting time after transradial coronary stenting with
      maximal antiplatelet therapy.
AB  - The optimal value of activated clotting time (ACT) during percutaneous coronary
      intervention (PCI) with unfractionated heparin remains controversial. No data are
      available on the relation between the ACT at the end of the procedure (final ACT)
      and the clinical outcomes after transradial PCI and maximal antiplatelet therapy.
      By dividing the final ACT values in tertiles, we analyzed the ischemic and
      bleeding events in 1,234 consecutive patients with acute coronary syndrome
      recruited in the EArly Discharge after Transradial Stenting of CoronarY Arteries
      (EASY) trial. All patients were pretreated with aspirin and clopidogrel. After
      radial sheath insertion, patients received 70 IU/kg unfractionated heparin.
      Abciximab was given before the first balloon inflation. The median final ACT
      value was 312 seconds (interquartile range 279 to 344). At 30 days, the rate of
      major adverse cardiac events, including death, myocardial infarction, and target
      vessel revascularization, from the lower to upper tertiles was 4%, 4%, and 2%,
      respectively (p = 0.16), and the rate of major bleeding was 2%, 1% and 0.7%,
      respectively (p = 0.20). During the 3 years of follow-up, the incidence of
      myocardial infarction was less in the tertile with the greatest ACT value (>330
      seconds) than in the other 2 tertiles (4%, 8%, and 8%, respectively; p = 0.038).
      Troponin-T and creatine kinase-MB release after PCI indicated that the effect was
      related to periprocedural myonecrosis protection. After adjustment for baseline
      and procedural differences, a final ACT of >330 seconds remained associated with
      a 47% relative reduction in myocardial infarction (odds ratio 0.53, 95%
      confidence interval 0.29 to 0.93, p = 0.024). Death and target vessel
      revascularization remained similar in all tertiles for < or =3 years. In
      conclusion, with the combination of aspirin, clopidogrel pretreatment, and
      abciximab, a final ACT value of >330 seconds appears protective against peri-PCI
      myonecrosis, and this benefit was maintained for < or =3 years. With a
      transradial approach and maximal antiplatelet therapy, greater ACT values did not
      correlate with an increased risk of bleeding.

PMID- 19840569
TI  - Predictors of increased radiation dose during percutaneous coronary intervention.
AB  - Radiation-induced injury is a potential unintended outcome of fluoroscopy
      supported cardiology procedures (e.g., percutaneous coronary intervention [PCI]).
      The injury might be deterministic in nature. Air kerma (AK) is considered an
      indicator of skin dose, and thus, an indicator for deterministic effects. Few
      studies have investigated the factors that contribute to an increased radiation
      dose, and none have used AK as a dependent variable. We studied the registry data
      of 967 consecutive patients (derivation model) undergoing ad hoc PCI. Linear and
      multiple regression analyses were performed to investigate which clinical,
      technical, and anatomic factors were associated with an increased AK. Multiple
      regression analyses were performed on an additional sample of 1,082 consecutive
      patients (validation model) to confirm the results. The variables found
      significant (multiple regression analyses) were radial access (mean increase in
      AK 253 mGy, 95% confidence interval [CI] 104 to 418, p = 0.0006), number of
      lesions treated (547 mGy, 95% CI 332 to 789, p < 0.0001), Type C lesions (132
      mGy, 95% CI, 26 to 246, p = 0.014), bifurcation lesions (280 mGy, 95% CI 104 to
      477, p = 0.0013), and chronic total occlusions (453 mGy, 95% CI 76 to 923, p =
      0.016). The validation model (n = 1,082) confirmed all but type C lesions (p =
      0.065). In conclusion, the present study has described factors that might
      contribute to an increased AK during PCI. In revealing a priori known factors
      associated with an increased radiation dose during PCI, physicians and patients
      might be more able to evaluate the risks and benefits of such a procedure.

PMID- 19840570
TI  - Prognostic accuracy of B-natriuretic peptide measurements and coronary artery
      calcium in asymptomatic subjects (from the Early Identification of Subclinical
      Atherosclerosis by Noninvasive Imaging Research [EISNER] study).
AB  - B-type natriuretic peptide (BNP) has prognostic implications in patients with
      acute and chronic cardiac symptoms. Its prognostic role in asymptomatic patients
      with evidence of subclinical disease remains unclear. The population of this
      study included 2,458 asymptomatic adults (47% women) with an average Framingham
      risk score of 8.8 +/- 7% who underwent computed tomographic evaluation of
      coronary artery calcium (CAC). BNP levels were measured using the Triage
      CardioProfilER panel method. Cox proportional-hazards models were used to
      estimate time to a cardiovascular (CV) event (n = 84; 16 deaths, 12 myocardial
      infarctions, 8 cerebrovascular accidents or transient ischemic attacks, and 48
      diagnoses of incident symptomatic coronary disease). Relative risk was
      calculated. The median follow-up time was 3.9 years (25th and 75th percentiles
      2.9 and 4.0). The relative hazard for a CV event ranged from 2.2 to 7.5 for BNP
      values of 40 to 99.9 and > or =100 pg/ml (p <0.0001) compared to BNP <40 pg/ml.
      Similarly, CAC score was also highly predictive of CV events, with elevated
      hazard ratios of 2.8- to 48.7-fold for scores of 11 to 100 to > or =1,000 (p
      <0.0001) compared to no CAC. In a stepwise model, BNP was the second greatest
      estimator of CV outcomes (p = 0.016) after CAC (p <0.0001), even in models that
      included blood pressure and age. Hypertension, age > or =65 years, and CAC
      contained 28.4%, 40.7%, and 56.8%, respectively, of BNP risk. The combination of
      BNP > or =100 pg/ml and CAC score > or =400 identified 52.4% and 35.7% of CV
      events in patients with hypertension and in elderly patients beyond the
      Framingham risk score. In conclusion, BNP and CAC are independently predictive of
      CV events.

PMID- 19840571
TI  - Effects of bariatric surgery on inflammatory, functional and structural markers
      of coronary atherosclerosis.
AB  - This study was designed to assess the effects of bariatric weight loss surgery on
      structural, functional, and inflammatory markers of coronary atherosclerosis.
      Obesity is a worldwide epidemic and an independent risk factor for coronary
      atherosclerosis. It remains unclear whether surgically induced weight loss
      reduces cardiovascular risk. This prospective study enrolled 50 consecutive
      subjects with morbid obesity who underwent Roux-en-Y gastric bypass surgery (GBS)
      after failed attempts at medical weight loss. Subjects were recruited through a
      comprehensive weight loss center affiliated with an academic tertiary care
      hospital. All subjects had body mass indexes > or =40 kg/m(2) or body mass
      indexes of 35 to 40 kg/m(2) with > or =2 co-morbid obesity-related conditions.
      Markers of coronary atherosclerosis, including brachial artery flow-mediated
      dilation, carotid intima-media thickness, and high-sensitivity C-reactive
      protein, were measured before GBS and 6, 12, and 24 months after GBS. There were
      statistically significant improvements in all measured markers of coronary
      atherosclerosis after GBS. The mean body mass index decreased from 47 to 29.5
      kg/m(2) at 24 months (p <0.001), the mean carotid intima-media thickness
      regressed from 0.84 to 0.50 mm at 24 months (p <0.001), mean flow-mediated
      dilation improved from 6.0% to 14.9% at 24 months (p <0.05), and mean high
      sensitivity C-reactive protein decreased from 1.23 to 0.65 mg/dl at 6 months (p
      <0.001) and to 0.35 mg/dl at 24 months (p <0.001). In conclusion, GBS results in
      significant improvements in inflammatory, structural, and functional markers of
      coronary atherosclerosis.

PMID- 19840572
TI  - Role of transesophageal echocardiography among patients with atrial fibrillation
      undergoing electrophysiology testing.
AB  - External or internal shocks administered to terminate ventricular arrhythmias as
      a part of electrophysiology or implantable cardioverter-defibrillator testing,
      can inadvertently cardiovert atrial fibrillation (AF). Moreover, anticoagulation
      therapy is often withheld in these patients in anticipation of an invasive
      procedure. The risk of embolic events during these procedures has not been well
      described. Accordingly, the present study was a prospective evaluation of the
      incidence of left atrial (LA) thrombus and AF cardioversion among patients
      undergoing ventricular arrhythmia assessment. Transesophageal echocardiography
      was routinely performed on 44 consecutive patients in AF with subtherapeutic
      anticoagulation undergoing electrophysiology or implantable cardioverter
      defibrillator testing. Arrhythmia induction was not performed when LA thrombus
      was present. The incidence and clinical predictors of thrombus, the inadvertent
      cardioversion of AF, and adverse events related to the procedure were assessed
      during the subsequent 4 to 6 weeks. Left atrial thrombus was observed in 12
      patients (27%). Sinus rhythm was restored in 29 patients (91%), at least
      transiently, who underwent testing with a shock delivered. No adverse neurologic
      or hemorrhagic complications were observed. Univariate analysis identified no
      predictors of LA thrombus or cardioversion to sinus rhythm. In conclusion, LA
      thrombus and cardioversion to sinus rhythm are common among patients with AF
      undergoing an evaluation of ventricular arrhythmias. Transesophageal
      echocardiography performed before the procedure in patients with subtherapeutic
      anticoagulation is warranted to minimize embolic complications. This strategy
      appears to be a safe method to guide diagnostic testing in this patient
      population.

PMID- 19840573
TI  - Use of low molecular weight heparin in pregnant women with mechanical heart
      valves.
AB  - There are a number of different anticoagulation options for pregnant women with
      mechanical heart valves. The purpose of this study was to examine maternal
      thromboembolic complications in women with mechanical valves treated with low
      molecular weight heparin (LMWH) throughout pregnancy. This was a substudy of a
      larger prospective cohort study of pregnant women with heart disease followed
      from 1998 to 2008. All pregnant women with mechanical left-sided valves who were
      treated with LMWH throughout pregnancy were included. Maternal thromboembolic
      events were defined as valve thrombosis, need for valve replacement, or stroke
      during pregnancy or postpartum (up to 6 months). Twenty-three pregnancies (17
      women) occurred in women treated with LMWH and low-dose aspirin: 15 in women with
      mechanical mitral valves, 9 in women with mechanical aortic valves, and 1 in a
      woman with both. There was 1 maternal thromboembolic event (4%), which resulted
      in maternal and fetal death. Five women (22%) developed other adverse cardiac
      events during pregnancy. Nine pregnancies (43%) had fetal or neonatal adverse
      events, 5 of which had favorable outcomes. Three pregnancies were complicated by
      postpartum hemorrhage. In conclusion, carefully monitored LMWH may be a suitable
      anticoagulation strategy in pregnant women with mechanical heart valves who are
      unwilling to use warfarin. However, this group of women remains at risk for
      maternal cardiac and fetal complications. The occurrence of valve thrombosis
      resulting in maternal death despite therapeutic anti-Xa levels highlights current
      limitations with anticoagulation in this population.

PMID- 19840574
TI  - Impact of right ventricular dilation on left ventricular myocardial deformation
      in patients after surgical repair of tetralogy of fallot.
AB  - Left ventricular (LV) dysfunction is 1 of the major determinants of late adverse
      clinical outcomes in patients after surgical repair of tetralogy of Fallot (TOF).
      The aim of this study was to test the hypothesis that LV myocardial deformation
      is impaired in patients after TOF repair and related to right ventricular (RV)
      dilation and exercise capacity. Longitudinal, radial, and circumferential LV
      myocardial deformation was determined using speckle-tracking echocardiography in
      23 postoperative patients with TOF and compared to that of 23 age-matched
      controls. Relations between LV strain and strain rate (SR) and RV volumes and
      exercise parameters were determined in patients. Compared to controls, patients
      had reduced global LV longitudinal, radial, and circumferential strain (all p
      values <0.05). Patients with significantly increased RV end-systolic volume (>2
      SDs higher than normal; n = 17) had reduced global LV circumferential strain (p =
      0.048) and SR (p = 0.038), but similar longitudinal and radial speckle-tracking
      echocardiographic parameters, compared to those without (n = 6). RV end-systolic
      volume was correlated inversely with global LV circumferential strain and SR (r =
      -0.58, p = 0.004, and r = -0.58, p = 0.005, respectively), while RV end-diastolic
      volume was correlated only with global LV circumferential strain (r = -0.43, p =
      0.047). In patients, the LV ejection fraction was correlated with global LV
      circumferential strain (r = 0.54, p = 0.01) and SR (r = 0.66, p = 0.001) but not
      with longitudinal or radial speckle-tracking echocardiographic parameters. Using
      multivariate analysis, global LV circumferential SR (beta = 0.66, p = 0.001) and
      male gender (beta = 0.46, p = 0.012) were identified as independent predictors of
      peak oxygen consumption. In conclusion, the negative impact of RV dilation on LV
      function relates to its influence on LV circumferential strain and SR in patients
      after TOF repair.

PMID- 19840575
TI  - Postnatal angiographic appearance of left ventricular myocardium in fetal
      patients with aortic stenosis having in-utero aortic valvuloplasty.
AB  - Fetal aortic valvuloplasty (FAV) is performed on the basis of the hypothesis that
      aortic stenosis leads to the impairment of left ventricular (LV) filling and
      growth. Given that most fetuses fail to exhibit normalization of LV growth even
      after successful FAV, better understanding of the associated LV myocardial
      pathology is indicated. Postnatal angiography was reviewed retrospectively for
      all patients who (1) underwent FAV for severe aortic stenosis and (2) had well
      opacified LV angiograms before any surgical intervention from 2000 to 2007. The
      angiographic appearance of the LV myocardium was described as either smooth or
      trabeculated in a total of 6 anatomic segments in 2 projections (anteroposterior
      and lateral). Twenty-four infants who underwent FAV had angiographic images
      appropriate for review. Of these, 4 (17%) had uniformly smooth LV myocardium,
      whereas 20 (83%) had deep trabeculations of > or =1 LV myocardial segment. Half
      of the infants (n = 13) had extensive trabeculations with the involvement of > or
      =4 segments. In all cases, the septal segments were smooth. In conclusion,
      patients after FAV have angiographically abnormal left ventricles, commonly
      involving extensive trabeculations of the free wall, but without septal
      involvement.

PMID- 19840576
TI  - Comparison of impact of prenatal versus postnatal diagnosis of congenitally
      corrected transposition of the great arteries.
AB  - Congenitally corrected transposition of the great arteries (CCTGA) in the absence
      of major cardiac anomalies is thought to have a good outcome, although this has
      not been well documented. The objective of the present study was to compare the
      characteristics and outcomes of patients with a prenatal diagnosis of CCTGA to
      the characteristics and outcomes of those diagnosed postnatally. The optimal
      outcome was defined as intervention-free survival. All patients with CCTGA
      diagnosed prenatally and postnatally from 1999 to 2006 at 2 tertiary care
      institutions were reviewed. Patients with a single ventricle, heterotaxy, or
      valvar atresia were excluded. The differences between groups were assessed using
      the t test and chi-square test. A total of 54 patients (16 prenatal with 14 live
      born and 39 postnatal) were included. The patients diagnosed prenatally were
      diagnosed at a median gestational age of 20 weeks (range 16 to 37). Two deaths in
      each group were due to heart failure. The intervention-free survival rate for the
      prenatal and postnatal groups at 1, 6, and 36 months was 79%, 45%, and 30% and
      85%, 61%, and 23%, respectively (p = NS). Of 37 patients, 14 (38%) underwent an
      arterial switch plus atrial baffling so that the morphologic left ventricle
      supported the systemic circulation, and 6 (16%) underwent repair of associated
      lesions so the morphologic right ventricle supported the systemic circulation; 4
      (11%) of the 37 patients had pacemaker only. Prenatal patients with >1 fetal
      echocardiogram (12 of 14) did not have progression before birth. In conclusion,
      CCTGA has a >70% risk of intervention in the first 3 years after birth. The
      outlook is guarded and has an important effect on prenatal counseling.

PMID- 19840577
TI  - Usefulness of various plasma biomarkers for diagnosis of heart failure in
      children with single ventricle physiology.
AB  - Children with single ventricle physiology have increased ventricular work and are
      at greater risk of developing heart failure than other children with congenital
      heart disease. However, the diagnosis of heart failure is difficult because few
      objective measures have been validated for this cohort. Plasma proteins have been
      identified as biomarkers of heart failure in adults with structurally normal
      hearts. However, whether these correlate similarly with heart failure in children
      with single ventricle physiology is unknown, because the etiology of adult heart
      failure is typically ischemic heart disease, but heart failure in these children
      is presumed to be due to primary myocardial dysfunction. We conducted a single
      site, cross-sectional observational study of young, single-ventricle patients.
      Clinical heart failure was defined as a Ross score >2. The association of several
      candidate biomarkers with heart failure was assessed using logistic regression
      analysis and receiver operating characteristic curves. Of the 29 included
      children, 9 (31%) were in clinical heart failure. A doubling of plasma B-type
      natriuretic peptide was associated with an odds ratio for heart failure of 2.17.
      The area under the receiver operating characteristic curve was 80.3%. A threshold
      value of > or =30 pg/ml showed both sensitivity and specificity for heart
      failure. Three other candidate biomarkers were not associated with clinical heart
      failure in this sample. In conclusion, plasma B-type natriuretic peptide is a
      sensitive biomarker for clinical heart failure in young children with single
      ventricle heart disease. The use of this plasma biomarker might facilitate
      detection of heart failure in these complex patients.

PMID- 19840578
TI  - Six-month follow-up of patients with in-hospital thrombocytopenia during heparin
      based anticoagulation (from the Complications After Thrombocytopenia Caused by
      Heparin [CATCH] registry).
AB  - Thrombocytopenia is a predictor of adverse outcomes in patients with acute
      coronary syndromes and in critically ill patients. The Complications After
      Thrombocytopenia Caused by Heparin (CATCH) registry was designed to explore the
      incidence, management, and clinical consequences of in-hospital thrombocytopenia
      occurring during heparin-based anticoagulation in diverse clinical settings. We
      conducted a prospective observational study of 37 United States hospitals
      participating in the CATCH registry to assess the relation of in-hospital
      thrombocytopenia to long-term outcomes. A total of 2,104 patients at increased
      risk of developing in-hospital thrombocytopenia or thrombosis were identified,
      and the 6-month mortality and rehospitalization rates were determined.
      Thrombocytopenia was not a significant predictor of 6-month mortality. In an
      adjusted model for in-hospital death in this cohort, thrombocytopenia had an odds
      ratio of 3.59 (95% confidence interval 2.24 to 5.77). The postdischarge mortality
      rate at 6 months was 9.7%. No significant difference was observed in the long
      term mortality between patients who developed thrombocytopenia and those who did
      not. Thrombocytopenia was a weak, but statistically significant, predictor of a
      composite of mortality and rehospitalization at 6 months (hazards ratio 0.80, 95%
      confidence interval 0.65 to 0.98, p = 0.03). In conclusion, the 6-month mortality
      rate among heparin-treated patients with thrombocytopenia is high, although the
      risk independently related to thrombocytopenia appears to be restricted to the
      acute hospital phase.

PMID- 19840579
TI  - A comparison of clopidogrel responsiveness in patients with versus without
      chronic renal failure.
AB  - We sought to compare the platelet responsiveness to clopidogrel between patients
      with chronic renal failure and those with normal renal function. We conducted a
      prospective, randomized, open-label, single-center trial. A total of 23 patients
      with normal renal function received a usual daily dose of 75 mg of clopidogrel
      (group I, 61 +/- 7 years). Also, 36 patients with chronic renal failure (60 +/- 5
      years) were divided into 2 groups according to their daily dose of clopidogrel: a
      daily dose of 75 mg of clopidogrel for 30 days (group II, n = 18) or a daily dose
      of 150 mg (group III, n = 18). The primary efficacy variables among the study
      groups using the VerifyNow P2Y12 assay were the P2Y12 reaction unit value and the
      percentage of inhibition. A significant difference was found in the P2Y12
      reaction unit value among the 3 groups (239 +/- 87 in group I, 308 +/- 70 in
      group II, 302 +/- 81 in group III (p = 0.013) and in the percentage of inhibition
      (35 +/- 20 in group I, 21 +/- 16 in group II, 23 +/- 14 in group III, p = 0.026).
      No significant difference was found in the P2Y12 reaction units or percentage of
      inhibition between groups II and III. In conclusion, platelet responsiveness to
      clopidogrel decreased more in patients with chronic renal failure than in those
      with normal renal function, and this decreased platelet responsiveness to
      clopidogrel was not improved by an increase in the clopidogrel dosage.

PMID- 19840580
TI  - Electrocardiographic screening in children with attention-deficit hyperactivity
      disorder.
AB  - Some investigators have suggested that children receiving stimulant medications
      to manage attention-deficit hyperactivity disorder should undergo screening
      electrocardiography to identify asymptomatic cardiac disease. However, no study
      to date has examined the efficacy and costs of this strategy. In the present
      study we sought to determine the utility of electrocardiographic screening in
      children with attention-deficit hyperactivity disorder. We reviewed the clinical
      experience of electrocardiographic screening of subjects with attention-deficit
      hyperactivity disorder <21 years of age from April to September 2008. Additional
      cardiac care and testing that resulted from an abnormal initial electrocardiogram
      were recorded. Screening electrocardiograms were obtained in 1,470 children with
      attention-deficit hyperactivity disorder and were interpreted as abnormal in 119
      subjects (8.1%). Further evaluation of these 119 subjects included 63
      transthoracic echocardiograms, 5 stress tests, and 9 Holter monitor studies.
      Cardiac disease was identified in 5 subjects (0.3% of entire cohort), yielding a
      positive predictive value of 4.2%. Cardiac diagnoses included ventricular pre
      excitation syndrome (n = 2), bicuspid aortic valve (n = 2), and moderate secundum
      atrial septal defect (n = 1). The mean cost of electrocardiographic screening
      including further testing for subjects with abnormal initial screen results was
      $58 per child. The mean cost to identify a true-positive result was $17,162. In
      conclusion, electrocardiographic screening for children with attention-deficit
      hyperactivity disorder can successfully identify cardiac disease in otherwise
      asymptomatic subjects, although the positive predictive value is low. Ongoing
      studies are needed to know what role electrocardiographic screening should play
      in the management of children with attention-deficit hyperactivity disorder.

PMID- 19840581
TI  - Frequency and impact of pulmonary hypertension in patients with obstructive sleep
      apnea syndrome.
AB  - The correlates and consequences of pulmonary hypertension (PH) associated with
      obstructive sleep apnea (OSA) are poorly understood. Patients undergoing
      pulmonary artery catheterization within 6 months of an overnight polysomnography
      showing OSA were included in the present analysis. A total of 83 patients with
      complete data were analyzed (no PH, n = 25 [30%]; PH, 58 [70%]; of these, 18 had
      a pulmonary capillary wedge pressure of <15 mm Hg). No significant differences
      were observed between the PH and no PH groups regarding age or apnea-hypopnea
      index. The correlates of PH were elevated right ventricular systolic pressure (p
      <0.001), body mass index (p = 0.026), female gender (p = 0.01), nocturnal
      desaturation (82% vs 18%), and forced vital capacity <70% (p = 0.04) on
      univariate analysis and female gender (p = 0.03), age <49 years (p = 0.02), body
      mass index of > or =26 kg/m(2) (p = 0.08), and right ventricular systolic
      pressure of > or =30 mm Hg (p <0.001) on multivariate analysis. Patients with PH
      had a lower 6-minute walk distance (285.5 +/- 122 m vs 343 +/- 213 m, p = 0.4).
      The survival rate at 1, 4, and 8 years for patients with PH was 93%, 75%, and 43%
      compared to 100%, 90%, and 76% for patients without PH, respectively. Patients
      with severe PH (n = 27; 33%) had more nocturnal desaturation (p = 0.045), worse
      pulmonary hemodynamics, and greater mortality (37%) than the groups with mild or
      moderate PH (16%) or no PH (16%). In conclusion, our results have shown that,
      although generally mild to moderate, severe PH can occur in patients with OSA.
      Female gender, younger age, obesity, and nocturnal desaturation were associated
      with PH. PH can cause functional limitations and increased mortality in patients
      with OSA.

PMID- 19840582
TI  - Is age really a non-modifiable cardiovascular risk factor?

PMID- 19840583
TI  - Death and dying in heart failure with normal ejection fraction.
AB  - The overall mortality rate in patients with heart failure with normal ejection
      fraction (HFNEF) appears to be comparable to that in patients with heart failure
      with reduced ejection fraction. In contrast to the latter group of patients,
      randomized trials with neurohumoral blockade in patients with HFNEF have failed
      to demonstrate reduction in mortality. This is at least in part related to the
      lower proportion of heart failure-related death in the overall population of
      patients with HFNEF. In conclusion, better characterization of patients with
      HFNEF at greatest risk for heart failure-related death and understanding the
      risks of the different modes of death would allow more effective use of specific
      heart failure medical or device therapy in patients with HFNEF.

PMID- 19840584
TI  - Reducing cardiovascular risks of nonsteroidal anti-inflammatory drugs by using
      topical formulations.

PMID- 19840585
TI  - Does personality disorder decrease the likelihood of remission in early-onset
      chronic depression?
AB  - BACKGROUND: The impact of personality disorders (PD) on the course of depression
      has been gaining interest among clinical researchers over the past decade. Recent
      observational studies have found that PD was associated with impaired social
      functioning and reduced likelihood of depression recovery. Elevated rates of PD
      have been noted in early-onset and chronic forms subtypes of depression. However,
      scant data exist regarding the link between PD and outcome for this depression
      subtype. METHODS: The National Epidemiological Survey on Alcohol and Related
      Conditions database was analyzed. This survey included 43 093 respondents, 18
      years and older, conducted in 2001 through 2002. Logistic regression was used to
      identify demographic and clinical predictors of remission in early-onset chronic
      depression. RESULTS: The absence of PD, having more years of education, and being
      married considerably improved the likelihood of remission. Paranoid personality
      disorder and obsessive-compulsive disorder were the only specific PD found to be
      associated with a reduced probability of remission. LIMITATIONS: Depression
      remission status may have biased the recollection of PD symptoms. Borderline
      personality disorder, narcissistic personality disorder, and schizotypal
      personality disorder were not assessed. CONCLUSIONS: This study suggests that PD
      are significant predictors of remission in early-onset chronic depression.

PMID- 19840586
TI  - A comparison of life events in suicidal and nonsuicidal adolescents and young
      adults with major depression and borderline personality disorder.
AB  - This retrospective study assessed the correlations between various types of
      stressful life events (SLE) and suicidal adolescents and young adults with major
      depressive disorder (MDD;22), borderline personality disorder (BPD;18), and
      nonsuicidal adolescents and young adults with MDD (20) and BPD (20). A community
      control group of 40 participants was also evaluated. The measurements used were
      Life Events Checklist, Childhood Sexual Abuse Questionnaire, Suicide Risk Scale,
      and Beck Depression Inventory. Suicidal participants experienced a greater number
      of total lifetime negative events compared with nonsuicidal participants,
      irrespective of diagnosis, including a greater amount of negative life events in
      the year before the suicide attempt compared with the year before referral in the
      nonsuicidal group. Participants with MDD reported more lifetime negative events
      than participants with BPD. Suicidal adolescents did not have more lifetime death
      related SLE than nonsuicidal adolescents, but MDD adolescents experienced more
      lifetime death-related SLE than BPD adolescents. Suicidal BPD participants
      reported more lifetime sex abuse-related SLE compared with nonsuicidal BPD
      participants. The complexity of the relationships between SLE and the interplay
      of both suicidality and underlying psychopathology is discussed with the relevant
      treatment implications.

PMID- 19840587
TI  - Postpartum obsessive-compulsive disorder: prevalence and clinical
      characteristics.
AB  - OBJECTIVE: The principal aims of this study were to examine the prevalence rate,
      clinical characteristics, and related factors of postpartum obsessive-compulsive
      disorder (OCD). METHOD: The subjects were a nonclinical sample of 400 postpartum
      women. They were interviewed from the 2nd up to the 26th week after birth. The
      Mini International Neuropsychiatric Interview was used for diagnosis of OCD, the
      Yale-Brown Obsessive-Compulsive Symptom Checklist was used to determine the types
      of obsessions and compulsions, and the Structured Clinical Interview for DSM-IV
      Axis I Disorders was used to diagnose comorbid depressive episode. RESULTS:
      Thirty-six (9%) of the sample met the diagnostic criteria for OCD according to
      the Mini International Neuropsychiatric Interview, and 9 (2.3%) reported
      postpartum onset OCD. Obsessive-compulsive disorder was more frequent in mothers
      with personal history of previous psychiatric disorder, somatic disease, or
      obstetric complication in pregnancy/birth, and who were multiparous. The most
      common obsessions were aggressive, contamination and miscellaneous, and
      compulsion for washing/cleaning and checking, and 38.9% have a comorbid
      depressive episode. CONCLUSION: Women have increased risk of OCD or obsessive
      compulsive symptoms in the postpartum period. For this reason, all women,
      particularly women with previous psychiatric history, somatic disease, or with
      complications in pregnancy or at the birth should be carefully screened for OCD
      in the postpartum period.

PMID- 19840588
TI  - Internet addiction: a descriptive clinical study focusing on comorbidities and
      dissociative symptoms.
AB  - AIMS: Internet addiction (IAD) is an emerging cause of morbidity and has been
      recently considered to merit inclusion in the Diagnostic and Statistical Manual
      of Mental Disorders, Fifth Edition. Given the paucity of knowledge about IAD, we
      conducted a descriptive clinical analysis of patients focusing on clinical,
      demographic features, and comorbidities. The detachment has been suggested as a
      reason for the attractiveness of the Internet; thus, we assessed dissociative
      symptoms and their association with IAD disability. DESIGN AND SETTING: A cohort
      of 50 adult outpatients were screened using the Internet Addiction Scale.
      Exclusion criterion was using the Internet for only one purpose such as gaming or
      gambling. PARTICIPANT: Nine women and 6 men constituted the sample of Internet
      addicts; each of them had a score of 70 or higher on the Internet Addiction
      Scale. MEASUREMENT: Comorbidities and subthreshold symptoms were screened
      carefully. Dissociative symptoms were analyzed with the Dissociative Experience
      Scale, and disability was assessed using the Sheehan Disability Scale. FINDINGS:
      Hours/week spent on the Internet were 42.21 +/- 3.09. Clinical diagnoses included
      14% attention deficit and hyperactivity disorder, 7% hypomania, 15% generalized
      anxiety disorder, 15% social anxiety disorder; 7% dysthymia, 7% obsessive
      compulsive personality disorder, 14% borderline personality disorder, and 7%
      avoidant personality disorder. One patient met criteria for binge eating
      disorder. Severity measures of IAD were associated with higher perception of
      family disability (r = 0.814; P <or= .001) and with higher Yale-Brown Obsessive
      Compulsive Severity score (r = 0.771; P <or= .001). Scores for the Dissociative
      Experience Scale were higher than expected (23.20 +/- 1.83) and were related to
      higher obsessive compulsive scores (r = 0.618; P <or= .001), hours per week on
      the Internet (r = 0.749; P <or= .001), and perception of family disability (r =
      0.677; P <or= .001). CONCLUSION: From a phenomenological point of view, IAD in
      our sample population seems to be more compulsory than rewarding or mood driven.
      Dissociative symptoms are related to severity and impact of IAD.

PMID- 19840589
TI  - Brief cognitive-behavioral therapy with fibromyalgia patients in routine care.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the effectiveness of
      a brief cognitive-behavioral therapy (CBT) group intervention for fibromyalgia
      syndrome in routine care. METHOD: Thirty-four female outpatients who participated
      in a 5- to 6-week group CBT program were assessed for depression (Beck Depression
      Inventory), anxiety (State-Trait Anxiety Inventory), coping strategies (Coping
      Questionnaire for Chronic Pain), physical functioning (Fibromyalgia Impact
      Questionnaire), and somatization (Health Attitude Survey) at 3 time points
      (baseline, pretreatment, and posttreatment) using a pre-post, quasi-experimental
      design. RESULTS: Twenty-three female outpatients (68% of the initial sample) for
      which data were available in all 3 time points were included in the analyses. No
      changes were found during the waiting period. During the treatment period, there
      were significant reductions in depression (P = .001) and anxiety (P = .006)
      symptoms and an increased use of distraction skills (P < .001). The analysis of
      rate of change showed a significant correlation between anxiety and depression (P
      = .004), but not between these variables and the use of distraction as a coping
      strategy. CONCLUSION: Brief group CBT is effective in reducing emotional distress
      in female patients with long-standing fibromyalgia syndrome in the context of
      routine care. Attention-distraction skills appear to be amenable to change by
      means of brief CBT, but further research is needed to clarify their contribution
      to short-term clinical improvement.

PMID- 19840591
TI  - Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, paranoid
      personality disorder diagnosis: a unitary or a two-dimensional construct?
AB  - OBJECTIVE: This article examines reliability and validity aspects of the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      paranoid personality disorder (PPD) diagnosis. METHOD: Patients with personality
      disorders (n = 930) from the Norwegian network of psychotherapeutic day
      hospitals, of which 114 had PPD, were included in the study. Frequency
      distribution, chi(2), correlations, reliability statistics, exploratory, and
      confirmatory factor analyses were performed. RESULTS: The distribution of PPD
      criteria revealed no distinct boundary between patients with and without PPD.
      Diagnostic category membership was obtained in 37 of 64 theoretically possible
      ways. The PPD criteria formed a separate factor in a principal component
      analysis, whereas a confirmatory factor analysis indicated that the DSM-IV PPD
      construct consists of 2 separate dimensions as follows: suspiciousness and
      hostility. The reliability of the unitary PPD scale was only 0.70, probably
      partly due to the apparent 2-dimensionality of the construct. Persistent
      unwarranted doubts about the loyalty of friends had the highest diagnostic
      efficiency, whereas unwarranted accusations of infidelity of partner had
      particularly poor indicator properties. CONCLUSIONS: The reliability and validity
      of the unitary PPD construct may be questioned. The 2-dimensional PPD model
      should be further explored.

PMID- 19840590
TI  - Population-based prevalence of smoking in psychiatric inpatients: a focus on
      acute suicide risk and major diagnostic groups.
AB  - OBJECTIVE: The aim of the study was to define the extent of current and lifetime
      smoking by diagnostic groups and suicide risk as reason for admission in a
      geographically defined psychiatric inpatient cohort. DESIGN: The study used a
      population-based retrospective chart review. METHODS: Smoking status and
      discharge diagnoses for Olmsted County, Minnesota, inpatients aged 18 to 65
      admitted for psychiatric hospitalization in 2004 and 2005 were abstracted from
      the electronic medical record. Diagnostic groups were compared to each other
      using chi(2) tests and Fisher exact test to analyze smoking status within the
      inpatient sample with significance defined as P <or= .05. RESULTS: Eighty percent
      (80.41) of our sample of 776 patients was hospitalized due to acute suicide risk.
      Discharge diagnostic group composition included affective disorders (80.3%),
      substance abuse disorders (36.1%), anxiety disorders (19%), psychotic disorders
      (16.4%), and personality disorders (10.3%). Of the sample, 72.2% had at least one
      comorbid disorder. Of the 776 patients, 356 (45.9%) were current smokers.
      Substance abuse and psychotic disorder diagnoses were significantly correlated
      with current smoking status (<.0001, .02) with 77.1% and 55.9%, respectively,
      being current smokers compared to other psychiatric inpatient groups. All
      diagnostic groups smoked at higher rates and had less success stopping than the
      US general population. CONCLUSION: Our findings clearly demonstrate
      stratification of current smoking and quit rates in psychiatric inpatient'
      diagnostic groups vs the US general population and Minnesota. Further research
      into the association between suicide risk, smoking, and mortality in the
      seriously mentally ill is necessary. Recognizing and addressing smoking in
      psychiatric patients in both hospital and outpatient settings is critical to
      addressing survival differences compared to the general population.

PMID- 19840592
TI  - Quality of life and psychopathology during the course of schizophrenia.
AB  - OBJECTIVE: This study evaluated a population of outpatients with stable
      schizophrenia to analyze if relationships between patterns of symptomatology and
      quality of life (QOL) change during the time course of illness. METHODS: We
      recruited 168 outpatients with stable schizophrenia, and we further divided our
      sample into 3 groups of patients (<or=36, 37-72, and >72 months of illness).
      Psychiatric assessment included the Quality of Life Scale, the Positive and
      Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the
      Clinical Global Impression-Severity Scale. All clinical variables significantly
      related to Quality of Life Scale scores were subsequently analyzed using a
      multiple stepwise regression to assess their independent contribution to QOL in
      the 3 patient groups. RESULTS: Quality of life and symptoms profiles were similar
      among patient groups. After controlling for potentially confounding variables,
      multiple regression revealed that depressive symptoms appeared to have a stronger
      relationship with QOL during the early 3-year course of the illness. In the
      period between 4 and 6 years of illness, negative symptoms were the most reliable
      predictors of QOL. After the 6-year course of illness, negative symptoms remained
      the most reliable predictors of QOL, together with severity of illness, whereas
      positive and depressive symptoms had a minor role. CONCLUSIONS: Despite similar
      QOL and symptoms profiles, these findings suggested that relationships among
      patterns of symptomatology and QOL change during the course of schizophrenia.

PMID- 19840593
TI  - Is there a measurement overlap between depressive symptoms and quality of life?
AB  - BACKGROUND: Previous studies found that depression is associated with a broad
      impairment in quality of life (QOL). This finding might be associated to a
      measurement overlap. METHODS: The objective of this study was to verify whether
      the items of the World Health Organization Quality of Life Instrument-Abbreviated
      version (WHOQOL-BREF), a measure of generic QOL, are invariant among patients
      having a current major depressive episode who come from primary care services. We
      investigated data from primary care services from the 6 countries (Australia,
      Brazil, Israel, Russia, Spain, and the United States) involved in the baseline
      sample of the Longitudinal Investigation of Depression Outcomes. The Rasch model
      was used to analyze items exhibiting differential item functioning (DIF) as a way
      of assessing invariance in relation to a depression factor defined by the
      diagnosis of depression using the Composite International Diagnostic Interview.
      In addition, the Center for Epidemiological Studies-Depression Scale (CES-D)
      score was correlated with the item and domain scores of the WHOQOL-BREF using the
      Pearson coefficient. RESULTS: The sample consisted of 2359 subjects, of which
      1193 had a confirmed diagnosis of a current major depressive episode. Of the 26
      items of the WHOQOL-BREF, 11 showed DIF due to the depression factor, and the
      physical domain presented more items displaying DIF. All Pearson coefficients
      between the WHOQOL-BREF item and domain scores and the CES-D score were weak and
      moderate (r = -0.13 to r = 0.43). CONCLUSIONS: Our findings indicate that most
      WHOQOL-BREF items do not exhibit DIF for a current major depressive episode and
      the variance associated with depression in this generic QOL measure is restricted
      to some facets of this construct. Thus, we recommend this restricted adjustment
      for depression in future analyses of this measure. Furthermore, our study
      indicates that researchers must measure QOL regardless of depression severity.

PMID- 19840594
TI  - Cloninger's temperament and character dimensions of personality in patients with
      major depressive disorder.
AB  - In this present study, we examined the relationship between the Cloninger's
      dimensional psychobiologic model of personality and depression in an outpatient
      population with major depressive disorder. Eighty-one depressed outpatients (67
      women, 14 men) and 51 healthy controls (35 women, 16 men) filled out the Turkish
      version of the Temperament and Character Inventory (TCI). Depression severity was
      evaluated by using the 17-item Hamilton Depression Rating Scale and the 21-item
      Beck Depression Inventory. Depressed patients exhibited statistically significant
      higher scores for harm avoidance and lower scores for self-directedness compared
      to healthy controls. Sentimentality (RD1) and dependence (RD4) subscale scores of
      reward dependence and spiritual acceptance (ST3) subscale of self-transcendence
      were significantly higher; attachment (RD3) subscale of reward dependence,
      responsibility (SD1), purposefulness (SD2), resourcefulness (SD3), and congruent
      second nature (SD5) subscales of self-directedness were significantly lower in
      the depressed group. In the depressed patient group, main effects of sex were
      significant for reward dependence and cooperativeness; the scores of both
      dimensions were higher for women. The Beck Inventory was positively correlated
      with harm avoidance and negatively correlated with novelty seeking and self
      directedness dimensions (P < .05). The duration of depression (16.33 +/- 20.18
      months) or the mean onset age of depression (28.68 +/- 8.11 years) did not show
      significant correlations with TCI scales. This study confirms the relationship
      between harm avoidance and depression and suggests a relationship between self
      directedness and depression.

PMID- 19840595
TI  - Novelty seeking among adult women is lower for the winter borns compared to the
      summer borns: replication in a large Finnish birth cohort.
AB  - OBJECTIVE: Earlier general population studies have shown that novelty seeking
      (NS) of the Temperament and Character Inventory (TCI) of personality is lower for
      persons born in winter compared to those born in summer, particularly for women.
      Here, we investigate if this result can be replicated in another population.
      METHOD: The Northern Finland 1966 Birth Cohort, comprising 4968 subjects (2725
      women, 2243 men), was investigated with regard to the temperament dimensions of
      the TCI and the season of birth. RESULTS: Novelty seeking and reward dependence
      (RD) showed significant variations according to the month of birth. We found that
      women born during winter have significantly lower levels of NS compared to women
      born during summer, with a minimum for the birth month November and maximum for
      May. These results are similar to those found in a previous Swedish study.
      Furthermore, our study showed that men born during spring had significantly lower
      mean scores of RD compared to men born during autumn, with a minimum for birth
      month March. This was in contrast to the Swedish study, where the minimum of RD
      was obtained for the birth month December. CONCLUSION: Women born in winter have
      lower NS as adults compared to women born in summer. Because NS is modulated by
      dopamine, this study gives further support to the studies in the literature that
      show that dopamine turnover for those born in winter is higher than for those
      born in summer.

PMID- 19840596
TI  - Temperament and character in subjects with obsessive-compulsive disorder.
AB  - BACKGROUND: The aims of this study were to evaluate the differences between
      personality traits of patients with obsessive-compulsive disorder (OCD) and
      normal controls using the Temperament and Character Inventory (TCI) and to
      examine the relationship of personality traits and the severity of obsessive
      compulsive (OC) symptoms. We also aimed to examine the influence a particular
      personality trait might have on the 5 factor-analyzed symptom dimension scores of
      OCD. METHOD: We recruited 130 patients with OCD and 185 age- and sex-matched
      normal controls. All subjects completed the TCI. Patients with OCD were assessed
      with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Depression
      Rating Scale, and the factor-analyzed symptom dimension scores from the Y-BOCS
      checklist. RESULTS: Patients with OCD had higher harm avoidance scores and lower
      self-directedness (SD), reward dependence (RD), and cooperativeness (C) scores
      than the controls. Lower SD scores and lower C scores were associated with OC
      symptom severity measured by the Y-BOCS after adjusting for age and depression
      severity. Hoarding dimension of OC symptoms was associated with lower SD scores
      and higher persistence (P) scores after adjusting for age, OC symptom severity,
      and depression severity. CONCLUSIONS: There were significant differences in TCI
      subscales between patients with OCD and controls. Particular personality traits
      may have an influence on the severity and the dimensions of OC symptoms.

PMID- 19840597
TI  - Relationship between lunar phases and serious crimes of battery: a population
      based study.
AB  - OBJECTIVE: The hypothesis of a lunar influence on human abnormal behavior is
      still widespread, although research has led to conflicting findings. Therefore, a
      population-based study to assess the influence of lunar phases on violent crimes
      was conducted. METHODS: The study included all serious crimes of battery
      (aggravated assaults) committed in Middle Franconia (Bavaria, Germany) between
      1999 and 2005 (n = 23 142). Data were analyzed regarding lunar phase, sex, and
      place of crime scene (outdoor vs indoor). RESULTS: No significant associations
      between full, absent, and the moon's interphases and serious crimes of battery
      could be detected. Furthermore, a Fourier analysis was conducted that failed to
      produce an association between violence and the moon's phases. DISCUSSION:
      Several possible explanations for the presented results are discussed including
      biological and social mechanisms. CONCLUSIONS: The present study fails to find a
      significant association between lunar phases and crimes of battery.

PMID- 19840598
TI  - Symptomatic determinants of insight in schizophrenia spectrum disorders.
AB  - Impaired insight in schizophrenia spectrum disorders has been linked to several
      psychopathologic features including positive symptoms, although not all
      dimensions of psychopathology have been studied and confounds from other symptoms
      have not been ruled out. In addition, the nature of the association between
      insight and specific positive symptoms, in particular delusions, remains unclear.
      The present investigation examined whether, in patients with schizophrenia
      spectrum disorders insight is associated with specific symptom dimensions
      including delusional severity. The factor structure was determined from scores of
      151 patients rated on the Signs and Symptoms of Psychotic Illness scale.
      Associations of the Signs and Symptoms of Psychotic Illness insight item with the
      resulting components and delusions were assessed using regression-based
      methodology. Principal component analysis revealed 4 orthogonal symptom clusters.
      Correlational analyses demonstrated that only depression/anxiety and psychomotor
      excitation were significantly related to insight. Hierarchical regression
      indicated that delusions explained unique variance in insight over and above
      depression/anxiety and psychomotor excitation. These results suggest that
      depression/anxiety is associated with better insight and that psychomotor
      excitation and delusions are associated with poorer insight.

PMID- 19840599
TI  - Latent class analysis of the Child Behavior Checklist Obsessive-Compulsive Scale.
AB  - The Obsessive-Compulsive Scale (OCS) of the Child Behavior Checklist (CBCL)
      predicts obsessive-compulsive disorder and is highly heritable. Latent class
      analysis (LCA) of the OCS was used to identify profiles within this 8-item scale
      and to examine heritability of those profiles. The LCA was performed on maternal
      CBCL reports of their 6- to 18-year-old children from 2 US nationally
      representative samples from 1989 (n = 2475, 50% male) and 1999 (n = 2029, 53%
      male) and from Dutch twins in the Netherlands Twin Registry at ages 7 (n = 10
      194, 49.3% male), 10 (n = 6448, 48.1% male), and 12 (n = 3674, 48.6% male) years.
      The heritability of the resultant classes was estimated using odds ratios of twin
      membership across classes. A 4-class solution fitted all samples best. The
      resulting classes were a "No or Few Symptoms" class, a "Worries and Has to Be
      Perfect" class, a "Thought Problems" class, and an "OCS" class. Within-class odds
      ratios were higher than across-class odds ratios and were higher for monozygotic
      than dizygotic twins. We conclude that LCA identifies an OCS class and that class
      is highly heritable using across-twin comparisons.

PMID- 19840609
TI  - Potential roles and clinical utility of prebiotics in newborns, infants, and
      children: proceedings from a global prebiotic summit meeting, New York City, June
      27-28, 2008.
AB  - Initial bacterial colonization, including colonization with health-positive
      bacteria, such as bifidobacteria and lactobacilli, is necessary for the normal
      development of intestinal innate and adaptive immune defenses. The predominance
      of beneficial bacteria in the gut microflora of breast-fed infants is thought to
      be, at least in part, supported by the metabolism of the complex mixture of
      oligosaccharides present in human breast milk, and a more adult-type intestinal
      microbiota is found in formula-fed infants. Inadequate gut colonization,
      dysbiosis, may lead to an increased risk of infectious, allergic, and autoimmune
      disorders later in life. The addition of appropriate amounts of selected
      prebiotics to infant formulas can enhance the growth of bifidobacteria or
      lactobacilli in the colonic microbiota and, thereby, might produce beneficial
      effects. Among the substrates considered as prebiotics are the oligosaccharides
      inulin, fructo-oligosaccharides, galacto-oligosaccharides, and lactulose. There
      are some reports that such prebiotics have beneficial effects on various markers
      of health. For example, primary prevention trials in infants have provided
      promising data on prevention of infections and atopic dermatitis. Additional well
      designed prospective clinical trials and mechanistic studies are needed to
      advance knowledge further in this promising field.

PMID- 19840610
TI  - A scientist track investigator program to support early career outcomes for
      clinician scientists.

PMID- 19840611
TI  - Cystic fibrosis: refining the approach to newborn screening.

PMID- 19840612
TI  - Automated adjustment of oxygen in ventilated preterm infants: turn on, tune in,
      ROP out?

PMID- 19840613
TI  - Breast-feeding and child lead exposure: a cause for concern.

PMID- 19840615
TI  - High-molecular-weight adiponectin in children born small- or appropriate-for
      gestational-age.
AB  - Longitudinal data collected from children ages 2 until 6 years, who were born
      appropriate-for-gestational-age or small-for-gestational-age, indicate that the
      latter have a normal body fat fraction and normal high-molecular-weight
      adiponectinemia at age 2 years and that they accumulate excess adipose tissue and
      have low adiponectin levels by age 4 to 6 years.

PMID- 19840614
TI  - Knowledge gaps and research needs for understanding and treating neonatal
      hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of
      Child Health and Human Development.

PMID- 19840616
TI  - COL4A1 mutation in preterm intraventricular hemorrhage.
AB  - Intraventricular hemorrhage is a common complication of preterm infants.
      Mutations in the type IV procollagen gene, COL4A1, are associated with cerebral
      small vessel disease with hemorrhage in adults and fetuses. We report a rare
      variant in COL4A1 associated with intraventricular hemorrhage in dizygotic
      preterm twins. These results expand the spectrum of diseases attributable to
      mutations in type IV procollagens.

PMID- 19840617
TI  - Chronic cheek lesions: an unusual manifestation of nontuberculous mycobacterial
      cevicofacial infection.
AB  - The characteristics of nontuberculous mycobacteria cheek lesions in 7 children
      were reviewed. The lesions usually presented as nontender erythematous nodules
      and were associated with a positive purified protein derivate tuberculin skin
      test. Mycobacterium haemophilum was isolated in 4 cases (57%) and Mycobacterium
      avium complex in 3 (43%). Cytology and imaging were noncontributory. Resolution
      was prolonged.

PMID- 19840618
TI  - Retrospective diagnosis of congenital cytomegalovirus infection at a school for
      the deaf by using preserved dried umbilical cord.
AB  - A retrospective diagnosis of congenital cytomegalovirus infection was made for 3
      of 26 students (12%) with either bilateral profound or severe sensorineural
      hearing loss at a School for the Deaf in Japan by detecting viral DNA with real
      time polymerase chain reaction from dried umbilical cords that had been preserved
      at home.

PMID- 19840619
TI  - Long-term growth hormone therapy in an adolescent boy with 45,X/46,XidicY(p11).
AB  - A 17-year-old boy with chromosomal mosaicism resulting in a
      45,X/46,X,idic(Y)(p11) karyotype came to medical attention at the age of 10 years
      because of short stature. He was treated with recombinant growth hormone for 6.6
      years and has achieved a near final adult height of 172.5 cm. His clinical
      features included second-degree hypospadias, some stigmata of Turner syndrome,
      and spontaneous progression through puberty. We report long-term use of growth
      hormone in a male adolescent with isodicentric Yq.

PMID- 19840620
TI  - CHAOS in the delivery room: a dire emergency.

PMID- 19840621
TI  - Mollaret meningitis associated with occipital dermal sinus.

PMID- 19840622
TI  - Electronic reminder systems increase screening for postpartum depression.

PMID- 19840623
TI  - Cognitive behavioral therapy prevents depression in at-risk adolescents.

PMID- 19840624
TI  - Problems with sleep, eating, and adherence to therapy are common among children
      with cystic fibrosis.

PMID- 19840625
TI  - Simple behavioral modification may be effective first-line treatment in
      resolution of nocturnal enuresis.

PMID- 19840626
TI  - Combination of epinephrine and dexamethasone may reduce hospitalization in
      children with bronchiolitis.

PMID- 19840627
TI  - Don't stop performing voiding cystourethrography in young children after the
      initial febrile urinary tract infection--at least not yet.

PMID- 19840628
TI  - The search for new diagnostic tests for neonatal sepsis.

PMID- 19840629
TI  - Indomethacin and retinopathy of prematurity.

PMID- 19840631
TI  - Heterogeneity in the clinical manifestations of mannose-binding lectin
      deficiency.

PMID- 19840632
TI  - Perceptual learning: functions, mechanisms, and applications.

PMID- 19840633
TI  - A review of cyclic fatigue testing of nickel-titanium rotary instruments.
AB  - INTRODUCTION: Fractured rotary nickel-titanium (NiTi) instruments have been
      classified into those that fail as a result of cyclic flexural fatigue or
      torsional failure or a combination of both. Clinically, NiTi rotary instruments
      are subjected to both torsional load and cyclic fatigue, and ongoing research
      aims to clarify the relative contributions of both factors to instrument
      separation. METHODS: To date, there is no specification or international standard
      to test cyclic fatigue resistance of endodontic rotary instruments. As a
      consequence, several devices and methods have been used to investigate in vitro
      cyclic fatigue fracture resistance of NiTi rotary endodontic instruments. In
      nearly all studies reported in the endodontic literature, the rotating instrument
      was either confined in a glass or metal tube, in a grooved block-and-rod
      assembly, or in a sloped metal block. RESULTS: There has been no mention of the
      "fit" of the instrument in the tube or groove. As the instrument is likely to be
      fitting loosely, the description of the radius of curvature in those studies is
      likely to be overstated (ie, the file was actually bent less severely than
      reported, adding a variability in the amount of flexural stress). CONCLUSIONS:
      This review analyzed several devices that have been used in endodontic literature
      for cyclic fatigue testing and found that differences in the methodology affected
      the fatigue behavior of rotary instruments and, consequently, the outcome of
      these studies. An international standard for cyclic fatigue testing of NiTi
      rotary instruments is required to ensure uniformity of methodology and comparable
      results.

PMID- 19840634
TI  - Randomized clinical trial comparing the effects of post placement on failure rate
      of postendodontic restorations: preliminary results of a mean period of 32
      months.
AB  - INTRODUCTION: The aim of this randomized clinical trial was to assess whether the
      placement of a fiber post (DT Light Post) (DT) and the amount of residual coronal
      dentin affect the time to failure of single-unit postendodontic restorations.
      METHODS: Ninety patients providing 120 teeth were selected. Three groups (n = 40)
      were defined on the basis of the amount of residual coronal dentin: 2-walls
      group, 2 or more coronal walls; 1-wall group, 1 coronal wall; no-wall group, no
      wall exceeding 2 mm above the gingival level. Within each group teeth were
      randomized and allocated to 2 intervention groups (n = 20), including subgroups
      no post (no root canal retention) and subgroups post (placement of DT). RESULTS:
      After a mean observation period of 32.4 (13.7) months in subgroups no post, the
      failure rates were 10%, whereas in subgroups post, failure rates of 7% were
      observed (P = .318). In no-wall group post placement significantly affected the
      time to failure of total restorations (P = .029, log-rank test). Teeth without
      post retention revealed a significantly higher failure rate (31%) compared with
      teeth restored with post retention (7%). CONCLUSIONS: Within the observation time
      of the present study, fiber post placement was efficacious to reduce failures of
      postendodontic restorations only with teeth that exhibited no coronal walls. Post
      insertion for teeth showing a minor substance loss should be critically
      reconsidered.

PMID- 19840635
TI  - Antibacterial efficacy of MTAD final rinse and two percent chlorhexidine gel
      medication in teeth with apical periodontitis: a randomized double-blinded
      clinical trial.
AB  - INTRODUCTION: Clinical assessment of the efficacy of novel root canal
      disinfection protocols is an important focus in endodontic research. This
      randomized double-blinded study assessed the antibacterial efficacy of a final
      rinse with BioPure MTAD (MTAD) and intracanal medication with 2% chlorhexidine
      gel (CHX) in teeth with apical periodontitis. METHODS: Canals in 30 teeth (single
      rooted and multi-rooted) were prepared by using 1.3% NaOCl, rinsed with MTAD or
      saline in random sequence, medicated with CHX for 7 days, irrigated with 1.3%
      NaOCl, and filled. Bacteriologic root canal samples were obtained by aspiration
      before (1A) and after (1B) canal preparation, after the final rinse (1C), after
      CHX was flushed (2A), and after final irrigation (2B). Bacteria were enumerated
      by epifluorescence-microscopy (EFM) by using 2 staining methods and by colony
      forming-unit (CFU) counts after 14 days of incubation. RESULTS: Bacterial counts
      (EFM) in 1B were greater than 95% decreased from 1A. Low bacterial densities in
      1B, 1C, 2A, and 2B did not differ significantly from each other. EFM counts were
      consistently higher than CFU counts. CONCLUSIONS: The final rinse with MTAD and
      medication with CHX did not reduce bacterial counts beyond levels achieved by
      canal preparation with NaOCl.

PMID- 19840636
TI  - Method to evaluate inflammatory root resorption by using cone beam computed
      tomography.
AB  - INTRODUCTION: The aim of this study was to evaluate a method to measure
      inflammatory root resorption (IRR) by using cone beam computed tomography (CBCT)
      scans. METHODS: IRR sites were classified according to root third and root
      surface, and IRR extension was measured on the axial, transverse, and tangent
      views of 3-dimensional CBCT scans by using the Planimp software. A 5-point (0-4)
      scoring system was used to measure the largest extension of root resorption. A
      total of 48 periapical radiographs and CBCT scans originally taken from 40
      patients were evaluated. The kappa coefficient was used to assess interobserver
      agreement and the chi(2) test to determine significant differences between the
      imaging methods. The level of significance was set at alpha = 1%. RESULTS: IRR
      was detected in 68.8% (83 root surfaces) of the radiographs and 100% (154 root
      surfaces) of the CBCT scans (P < .001). The extension of IRR was >1-4 mm in 95.8%
      of the CBCT images and in 52.1% of the images obtained by using the conventional
      method (P < .001). CONCLUSIONS: CBCT seems to be useful in the evaluation of IRR,
      and its diagnostic performance was better than that of periapical radiography.

PMID- 19840637
TI  - A prospective, randomized, double-blind comparison of the anesthetic efficacy of
      two percent lidocaine with 1:100,000 and 1:50,000 epinephrine and three percent
      mepivacaine in the intraoral, infraorbital nerve block.
AB  - INTRODUCTION: The purpose of this prospective, randomized, double-blind study was
      to compare the anesthetic efficacy of 2% lidocaine with 1:100,000 epinephrine, 2%
      lidocaine with 1:50,000 epinephrine, and 3% mepivacaine in the intraoral,
      infraorbital nerve block. METHODS: Forty subjects randomly received intraoral,
      infraorbital nerve blocks by using a cartridge of 2% lidocaine with 1:100,000 or
      1:50,000 epinephrine and a cartridge of 3% mepivacaine at 3 separate appointments
      spaced at least 1 week apart. The anteriors, premolars, and first molar were pulp
      tested in 4-minute cycles for a total of 60 minutes. RESULTS AND CONCLUSIONS: The
      intraoral, infraorbital nerve block was ineffective in providing profound pulpal
      anesthesia of the maxillary central incisor, lateral incisor, and first molar.
      Successful pulpal anesthesia of the canine and first and second premolars ranged
      from 75%-92% by using 2% lidocaine with 1:100,000 and 1:50,000 epinephrine.
      However, pulpal anesthesia did not last for 60 minutes. The use of 3% mepivacaine
      provided a shorter duration of anesthesia than the lidocaine formulations with
      epinephrine in the canines and premolars.

PMID- 19840638
TI  - Outcome of surgical endodontic treatment performed by a modern technique: a meta
      analysis of literature.
AB  - INTRODUCTION: Numerous studies dealing with the outcome of surgical endodontic
      treatment have been published. However, study design, treatment protocols, follow
      up periods, and inclusion and exclusion criteria are extremely variable. Thus,
      variable and confusing results have been reported. The aim of the present study
      was to assess the outcome of surgical endodontic treatment performed with a
      modern technique and to evaluate factors influencing the outcome by means of a
      meta-analysis. METHODS: An exhaustive literature search combined with strict
      inclusion and exclusion criteria was undertaken to identify prospective case
      series or randomized clinical trials that deal with surgical endodontic
      treatment. RESULTS: A successful outcome in a follow-up of more than 1 year
      postoperatively was 91.6%. Age, gender, tooth type, root-end filling material,
      and magnification type had no significant effect on the proportion of success.
      CONCLUSIONS: Surgical endodontic treatment done by using a modern technique is a
      predictable treatment. Additional large-scale prospective clinical studies are
      needed to evaluate possible predictors of success and failure.

PMID- 19840639
TI  - Technique acquisition in the use of two thermoplasticized root filling methods by
      inexperienced dental students: a microcomputed tomography analysis.
AB  - INTRODUCTION: Limited endodontic experiences in dental schools suggest the need
      for easy-to-learn techniques. Therefore, two simplified root filling methods were
      assessed for adequacy and expediency when performed by inexperienced students.
      METHODS: Eight students were trained (45-minute lecture and 90-minute practice)
      in use of ProTaper Obturators (PTO) and System-B/Calamus (SBC). They subsequently
      filled the root canals in two extracted, single-rooted teeth per method (n = 32).
      Canals were preshaped and prefitted with obturators and master cones. The volume
      of root-filling voids determined by microcomputed tomography imaging in 1-mm
      increments, time to complete fillings, and students' responses in questionnaires
      were analyzed (independent-sample t test and Mann-Whitney U test). RESULTS: PTO
      had a significantly smaller void volume in the apical 6 mm of canals (P < 0.001),
      required significantly shorter time (P < 0.001), and was perceived as easier to
      learn and use but less likely to be favored after graduation than SBC.
      CONCLUSION: These results suggested that the PTO root filling method was
      particularly suitable for teaching when endodontic experiences available for
      students are limited.

PMID- 19840640
TI  - Real-time polymerase chain reaction quantification of Porphyromonas gingivalis
      and Tannerella forsythia in primary endodontic infections.
AB  - INTRODUCTION: Porphyromonas gingivalis and Tannerella forsythia are anaerobic
      bacteria commonly involved in root canal infections. Although previous
      investigations have assessed these species by strictly qualitative approaches,
      accurate determination of their cell levels by a sensitive quantitative technique
      may contribute with additional information regarding relevance in pain of
      endodontic origin. METHOD: The root canal levels of P. gingivalis, T. forsythia,
      and total bacteria were investigated by a quantitative polymerase chain reaction
      (PCR) assay based on unique copy molecular markers. A total of 32 symptomatic (n
      = 14) and asymptomatic (n = 18) cases of endodontic infections were analyzed.
      Root canal samples were collected; genomic DNA was extracted and submitted to
      SYBR Green I real-time PCR targeting the rgpB (P. gingivalis), bspA (T.
      forsythia), and rpoB (total bacteria) single copy genes. RESULTS: Overall, P.
      gingivalis, T. forsythia, and the coexistence of both species were encountered in
      28%, 66%, and 22% of the subjects, respectively. P. gingivalis and T. forsythia
      levels ranged from 5.65 x 10(-6) to 1.20 x 10(-2) and from 5.76 x 10(-6) to 1.35
      x 10(-1). T. forsythia was highly prevalent and numerous in the study groups,
      whereas P. gingivalis was moderately frequent and less abundant, displaying 19
      fold lower average levels than the former. CONCLUSIONS: The endodontic levels of
      P. gingivalis and T. forsythia, individually or in conjunction, did not display
      significant associations with the manifestation of pain of endodontic origin.

PMID- 19840641
TI  - A retrospective clinical and radiographic study on healing of periradicular
      lesions in patients taking oral bisphosphonates.
AB  - INTRODUCTION: Bisphosphonates have been related to impaired bone remodeling. The
      impact of oral bisphosphonates on periradicular healing has not been studied. The
      purpose of this study was to evaluate the healing of periradicular lesions in
      patients taking oral bisphosphonates after root canal therapy. METHODS: Thirty
      four teeth with preoperative periradicular radiolucencies were identified in
      patients undergoing oral bisphosphonate therapy. These cases were examined
      clinically and radiographically to determine treatment outcome. Thirty-eight
      control teeth were selected from a pool of patients not taking bisphosphonates.
      Nonsurgical root canal treatment and retreatment was performed by endodontic
      residents and undergraduate dental students at Baylor College of Dentistry using
      nonstandardized protocols. RESULTS: In the bisphosphonate group, 73.5% of the
      lesions healed, whereas the control cases had a healing rate of 81.6%. There was
      no statistically significant difference between the groups (p > 0.05).
      CONCLUSION: The results of this preliminary short-term study suggest that
      patients taking long-term oral bisphosphonates can expect a satisfactory outcome
      with evidence of periradicular healing after conventional root canal treatment.
      Thus, root canal treatment may be considered a safe and realistic alternative to
      extraction in patients on bisphosphonate therapy.

PMID- 19840642
TI  - Fibroblast growth factor-2 regulates the cell function of human dental pulp
      cells.
AB  - INTRODUCTION: Homeostasis and tissue repair of dentin-pulp complex are attributed
      to dental pulp tissue and several growth factors. Dental pulp cells play a
      pivotal role in homeostasis of dentin-pulp complex and tissue responses after
      tooth injury. Among these cytokines, fibroblast growth factor (FGF)-2 has
      multifunctional biologic activity and is known as a signaling molecule that
      induces tissue regeneration. In this study, we examined the effects of FGF-2 on
      growth, migration, and differentiation of human dental pulp cells (HDPC).
      METHODS: HDPC were isolated from healthy dental pulp. Cellular response was
      investigated by [(3)H]-thymidine incorporation into DNA. Cytodifferentiation was
      examined by alkaline phosphatase (ALPase) assay and cytochemical staining of
      calcium by using alizarin red. Migratory activity was determined by counting the
      cells migrating into cleared area that had introduced with silicon block.
      RESULTS: FGF-2 activated HDPC growth and migration but suppressed ALPase activity
      and calcified nodule formation. Interestingly, HDPC, which had been pretreated
      with FGF-2, showed increased ALPase activity and calcified nodule formation when
      subsequently cultured without FGF-2. These results suggest that FGF-2 potentiates
      cell growth and accumulation of HDPC that notably did not disturb
      cytodifferentiation of the cells later. Thus, FGF-2 is a favorable candidate for
      pulp capping agent. CONCLUSIONS: These results provide new evidence for the
      possible involvement of FGF-2 not only in homeostasis but also in regeneration of
      dentin-pulp complex.

PMID- 19840643
TI  - Stem cell proliferation pathways comparison between human exfoliated deciduous
      teeth and dental pulp stem cells by gene expression profile from promising dental
      pulp.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) have been used for clinical
      application in tissue engineering and regenerative medicine (TERM). To date, the
      most common source of MSCs has been bone marrow. However, the bone marrow
      aspirate is an invasive and painful procedure for the donor. Thus, the
      identification and characterization of alternative sources of MSCs are of great
      importance. This study focused on the characterization of stem cells from human
      exfoliated deciduous teeth (SHED) compared with dental pulp stem cells (DPSCs)
      and bone marrow-derived mesenchymal stem cells (BMMSCs). METHODS: We have
      compared "stemness" such as the proliferation rate and the expression of stem
      cell marker of DPSCs, SHED, and BMMSCs. In addition, gene expression profile of
      DPSCs and SHED were analyzed by using DNA microarray. RESULTS: All cells isolated
      from the three sources exhibited MSC characteristics including a fibroblastic
      morphology, and the expression of mesenchymal stem-cell markers. The
      proliferation rate of SHED was significantly higher than that of DPSCs and BMMSCs
      (P < 0.05). The comparison of the gene expression profiles indicated 4386 genes
      with a changed expression between DPSCs and SHED by 2.0-fold or more. Higher
      expression in SHED was observed for genes that participate in pathways related to
      cell proliferation and extracellular matrix, including several cytokines such as
      fibroblast growth factor and tumor growth factor beta. CONCLUSIONS: Because of
      its advantages of a higher proliferation capability, abundant cell supply, and
      painless stem cell collection with minimal invasion, SHED could be a desirable
      option as a cell source for potential therapeutic applications.

PMID- 19840644
TI  - Effect of intraosseous anesthesia on control of hemostasis in pigs.
AB  - INTRODUCTION: Intraosseous anesthesia is used to deliver anesthetic into
      cancellous bone adjacent to the root apices. No study has assessed the effect of
      this anesthetic technique on hemostasis. The purpose of this study was to compare
      the amount of bleeding from soft tissue and bone in pig jaws after preoperative
      intraosseous or infiltration anesthesia with 2% lidocaine containing 1:50,000
      epinephrine. METHODS: Twelve pigs were divided into 3 groups. The first group
      received infiltration anesthesia on one half of the jaw and no anesthesia on the
      other half. The second group received intraosseous anesthesia on one half of the
      jaw and no anesthesia on the other half. The third group received infiltration
      anesthesia on one half of the jaw and intraosseous anesthesia on the second half.
      Blood was collected during flap reflection to measure the volume of soft tissue
      bleeding. Osteotomies were then prepared with blood collected from the surgical
      site to measure the volume of osseous bleeding. RESULTS: The median soft tissue
      blood loss observed in animals receiving infiltration anesthesia (1.14 mL) was
      significantly less as compared with animals that received no anesthesia (4.49 mL)
      or intraosseous anesthesia (2.45 mL). Compared with median hard tissue blood loss
      observed in animals without anesthesia (1.51 mL), significantly less blood loss
      was observed in animals receiving either infiltration anesthesia (0.67 mL) or
      intraosseous anesthesia (0.76 mL). CONCLUSIONS: Infiltration anesthesia resulted
      in significantly less soft tissue bleeding (p = .004) as compared with no
      anesthesia. Infiltration and intraosseous anesthesia resulted in significantly
      less osseous bleeding than the use of no anesthetic (p < .001). The volume of
      blood loss for each animal was shown to be below the maximum safe volume of blood
      loss for a single procedure.

PMID- 19840645
TI  - Effect of age and extrinsic microenvironment on the proliferation and osteogenic
      differentiation of rat dental pulp stem cells in vitro.
AB  - INTRODUCTION: It is suggested that dental pulp stem cells (DPSCs) possess
      pluripotent differentiation and self-renewal capacity and play a crucial role in
      maintaining dental pulp homeostasis. However, little is known about the age
      related changes of DPSCs, and whether aging and its microenvironment are
      associated with DPSCs remains a question. In this study, age-related changes in
      proliferation and osteogenic differentiation ability of rat DPSCs were assessed.
      METHODS: To examine the influence of microenvironment factors on different ages
      of DPSCs, we exposed adult rat DPSCs to juvenile rat dental pulp cell-conditioned
      medium (DPC-CM), and juvenile DPSCs were exposed to adult DPC-CM. Morphologic
      appearance, colony-forming assay, cell cycle analysis, 3-(4,5-dimethyl-thyazol-2
      yl)-2,5-diphenyltetrazolium, gene expression, and mineralization assay after
      osteogenic induction of DPSCs were evaluated. RESULTS: DPSCs isolated from the
      juvenile donors displayed increased proliferation and decreased osteogenic
      differentiation ability compared with the adult DPSCs. Interestingly, adult DPSCs
      induced by juvenile DPC-CM demonstrated enhanced proliferation but decreased
      osteogenic differentiation ability, whereas DPSCs from juvenile donors induced by
      adult DPC-CM showed decreased proliferation but enhanced osteogenic
      differentiation ability. CONCLUSIONS: Our data suggest that age-related changes
      of DPSCs should be taken into account when DPSCs are intended to be used for
      investigations and application. Furthermore, the activity of DPSCs can be
      modulated by the extrinsic microenvironment.

PMID- 19840646
TI  - In vitro bioactivity and biocompatibility of dicalcium silicate cements for
      endodontic use.
AB  - INTRODUCTION: The purpose of this study was to examine the in vitro bioactivity
      and biocompatibility of sol-gel-derived dicalcium silicate cements. METHODS: The
      morphology, phase composition, and compressive strength of the novel cement were
      investigated after immersion in a simulated body fluid for different periods of
      time. Cement biocompatibility was evaluated by incubating the cement specimens
      with MG63 human osteoblast-like cells. RESULTS: After immersion in a simulated
      body fluid as little as 1 hour, the cements were covered with clusters of bone
      like apatite spherulites. The characteristic peaks of apatite at 2theta = 25.9
      degrees and 31.8 - 32.9 degrees appeared. The compressive strength of the cement
      was increased from the initial strength value of 12.3 MPa to 1-day strength value
      of 20.2 MPa; these values were significantly different (P < .05). The MG63 cell
      viability increased 15% and 23% on the cement surfaces when compared with the
      control on hour 6 and day 7 of incubation, respectively. The cells appeared flat
      and exhibited intact, well-defined morphology on the cement surface. CONCLUSIONS:
      Both bioactivity and biocompatibility of the dicalcium silicate cement
      consistently make it a potential candidate for endodontic use.

PMID- 19840647
TI  - The effect of argon and nitrogen ion implantation on nickel-titanium rotary
      instruments.
AB  - INTRODUCTION: This qualitative study investigated the effect of N(2)(+) and Ar(+)
      ion implantation on morphologic alterations and fatigue resistance in Pro Taper
      S1 NiTi (Dentsply-Maillefer, Ballaigues, Switzerland) rotary instruments.
      METHODS: Instruments were divided into three groups: N(2)(+) implanted, Ar(+)
      implanted, and unmodified control group. All instruments were used to prepare
      five curved canals in epoxy resin blocks with brushing motion. The instruments
      were examined in a scanning electron microscope (SEM) before use, after first
      use, and after the fifth use. A more demanding cyclic fatigue test was
      undertaken, submitting the instruments to 15-second periods of continuous
      rotation inside the curved canals without a brushing motion. Crack formation was
      analyzed with the SEM, and the number of 15-second periods required to fracture
      each instrument was recorded. RESULTS: No significant morphologic alterations
      were observed in the instruments after the preparation of five canals. Crack
      density was similar in all groups. In the subsequent cyclic fatigue test,
      instruments implanted with nitrogen performed worse than those implanted with
      argon and the control group. Fracture faces show differences in the fracture
      modes. CONCLUSIONS: Ar(+) implantation improved the performance of S1 files
      moderately, whereas nitrogen ion-implanted files performed worse in the fatigue
      test. A reduction in file performance seems to be caused by nitrogen diffusion in
      the grain boundaries, instead of the desired improvement caused by titanium
      nitride formation.

PMID- 19840648
TI  - Evaluation of dentinal tubule penetration after the use of dentin bonding agent
      as a root canal sealer.
AB  - INTRODUCTION: The purpose of this study was to compare the effectiveness of
      Excite DSC (Ivoclar Vivadent, Schaan, Liechtenstein), a dentin bonding agent,
      with AH-26 (Dentsply, Detrey, Germany) as a root canal sealer by evaluating the
      penetration depth into the dentinal tubules and the tag density of the two
      compounds. METHODS: Forty-two extracted, single-rooted premolars were prepared
      and randomly obturated with either Excite DSC (n = 20) or AH-26 (n = 20). Two
      teeth were filled without sealer and used as controls. Randomly, one half of the
      specimens in each group (n = 10) was sectioned 3 days after obturation (short
      term), and the other half (n = 10) was sectioned after 3 months (long-term). The
      specimens were sectioned perpendicular to the long axis in two regions and
      prepared for observation using scanning electron microscopy. RESULTS: In the
      short-term evaluation, the mean penetration depth of AH-26 in the apical sections
      (520.48 micromol/L) was significantly higher than that of Excite DSC (0.00
      micromol/L). In the long-term evaluation, AH-26 exhibited a significantly greater
      depth of penetration in both the apical (797.74 micromol/L) and middle sections
      (1162.11 micromol/L) than Excite DSC (321.43 micromol/L and 657.72 micromol/L,
      respectively). CONCLUSION: AH-26 showed more dentinal tubule penetration depth
      than Excite DSC in both evaluation periods.

PMID- 19840649
TI  - Endodontic antimicrobial photodynamic therapy: safety assessment in mammalian
      cell cultures.
AB  - OBJECTIVES: The purpose of this study was to assess the in vitro synergistic
      effect of methylene blue (MB) and red light on human gingival fibroblasts and
      osteoblasts with parameters similar to those that may be applied in a clinical
      setting for endodontic disinfection. MATERIALS AND METHODS: Both cell types were
      sensitized with 50 microg/mL MB followed by exposure to red light at 665 nm for 5
      minutes with an irradiance of 10, 20, and 40 mW/cm(2). After photodynamic therapy
      (PDT), cell viability and mitochondrial activity were evaluated by the neutral
      red and MTT assay, respectively. The assessment of PDT-induced apoptosis was
      investigated by western blot analysis using cleaved poly(ADP-ribose) polymerase
      specific antibodies. RESULTS: Light at 20 and 40 mW/cm(2) with MB had modest
      effects at 24 hours on osteoblasts in both assays, whereas sodium hypochlorite
      completely eliminated cells. Western blot analysis revealed no signs of apoptosis
      in either cell type. CONCLUSION: The data suggest that there is a safe
      therapeutic window whereby PDT can inactivate endodontic pathogens without
      affecting host cell viability.

PMID- 19840650
TI  - Comparison of the efficacy of maleic acid and ethylenediaminetetraacetic acid in
      smear layer removal from instrumented human root canal: a scanning electron
      microscopic study.
AB  - INTRODUCTION: The aim of this study was to assess, by scanning electron
      microscopic (SEM) analysis, the ability of 17% EDTA and 7% maleic acid in the
      removal of the smear layer from the human root canal system. METHODS: Eighty
      single-rooted human anterior teeth were subjected to standardized root canal
      instrumentation (step-back technique) and were irrigated with 2.5% NaOCl after
      each instrument. Based on the final irrigating solution used, samples were
      divided randomly into three groups: (1) the EDTA group: 17% EDTA+ 2.5% NaOCl (n =
      30), (2) the maleic acid group: 7% maleic acid + 2.5% NaOCl (n = 30), and (3) the
      control group: 0.9% saline (n = 20). After final irrigation, teeth were prepared
      for SEM analysis to evaluate the cleaning of the coronal, middle, and apical
      thirds of radicular dentin by determining the presence or absence of smear layer.
      The data was statistically analyzed using the Kruskall-Wallis test. RESULTS: At
      the coronal and middle thirds, there was no significant difference between EDTA
      and maleic acid. Both were equally efficient in the removal of smear layer. In
      the apical third, maleic acid showed significantly better smear layer removing
      ability than EDTA. CONCLUSION: Final irrigation with 7% maleic acid is more
      efficient than 17%EDTA in the removal of smear layer from the apical third of the
      root canal system, which is a crucial area for disinfection.

PMID- 19840651
TI  - Evaluation of the effects of endodontic materials on fibroblast viability and
      cytokine production.
AB  - INTRODUCTION: Recently, a new sealer composed of Portland cement named Endo-CPM
      Sealer was developed. The aim of this study was to investigate the effects of
      Endo-CPM-Sealer (EGEO SRL, Buenos Aires, Argentina), Sealapex (Sybron Endo,
      Glendora, CA), and Angelus MTA (Angelus, Londrina, Brazil) on cell viability and
      cytokine (interleukin [IL]-1beta and IL-6) production by mouse fibroblasts.
      METHODS: Millipore culture plate inserts with polyethylene tubes filled with
      materials were placed into 24-well cell culture plates with mouse fibroblasts.
      Cells cultured with only empty polyethylene tubes were used as the control. After
      24 hours, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was
      used to evaluate the cell viability. For cytokine assay, mouse fibroblasts were
      incubated in 24-well flat-bottom plates with set material disks at the bottom.
      Cells cultured without the material disks served as the negative control. After
      24 hours of incubation, culture media were collected for cytokine evaluation by
      using an enzyme-linked immunosorbent assay. The data were statistically analyzed
      by analysis of variance and Bonferroni correction. RESULTS: Endo-CPM-Sealer,
      Sealapex, and Angelus MTA did not inhibit the cell viability. All materials
      induced IL-6 releasing, but the amount was not statistically significant compared
      with the control group. Angelus MTA induced IL-1beta releasing significantly more
      than the control. CONCLUSIONS: All materials were not considered cytotoxic in
      fibroblast culture.

PMID- 19840652
TI  - In vitro evaluation of the effectiveness of ProTaper universal rotary retreatment
      system for gutta-percha removal with or without a solvent.
AB  - INTRODUCTION: Effective removal of gutta-percha in endodontic retreatment is a
      significant factor to ensure a favorable outcome from failed procedures. The
      purpose of this study was to evaluate the efficacy of a nickel-titanium rotary
      instrument system with or without a solvent versus stainless steel hand files for
      gutta-percha removal. METHODS: Forty extracted human maxillary anterior teeth
      were prepared and filled. They were divided into 4 groups: Gates-Glidden and K
      files, Gates-Glidden and K-files with chloroform, ProTaper Universal rotary
      retreatment system, and ProTaper Universal rotary retreatment system with
      chloroform. The operating time was recorded. The teeth were longitudinally
      sectioned and photographed. The images were analyzed and the filling remnants
      were quantified by using the IMAGE TOOL software. RESULTS: With Kruskall-Wallis
      test, statistical analysis showed that there was no significant difference
      between the techniques in regard to the amount of the endodontic filling remnants
      (P < .05); however, the ProTaper Universal rotary retreatment system was faster
      than the hand files (P < .05). CONCLUSIONS: All of the techniques proved helpful
      for the removal of endodontic filling material, and they were similar in material
      remaining after retreatment, but the ProTaper Universal rotary retreatment system
      without chloroform was faster.

PMID- 19840654
TI  - Metallurgical characterization of a new nickel-titanium wire for rotary
      endodontic instruments.
AB  - INTRODUCTION: A novel thermomechanical processing procedure has been developed
      that yields a superelastic (SE) nickel-titanium (NiTi) wire (M-Wire) that
      laboratory testing shows has improved mechanical properties compared with
      conventional SE austenitic NiTi wires used for manufacture of rotary instruments.
      The objective of this study was to determine the origin of the improved
      mechanical properties. METHOD: Specimens from 2 batches of M-Wire prepared under
      different processing conditions and from 1 batch of standard-processed SE wire
      for rotary instruments were examined by scanning transmission electron
      microscopy, temperature-modulated differential scanning calorimetry, micro-x-ray
      diffraction, and scanning electron microscopy with x-ray energy-dispersive
      spectrometric analyses. RESULTS: The processing for M-Wire yields a
      microstructure containing martensite, that the proportions of NiTi phases depend
      on processing conditions, and that the microstructure exhibits pronounced
      evidence of alloy strengthening. CONCLUSIONS: The presence of Ti(2)Ni
      precipitates in both microstructures indicates that M-Wire and the conventional
      SE wire for rotary instruments are titanium-rich.

PMID- 19840653
TI  - Rotary nickel-titanium GT and ProTaper files for root canal shaping by novice
      operators: a radiographic and micro-computed tomography evaluation.
AB  - INTRODUCTION: The purpose of this study was to assess canal preparation outcomes
      in vitro by novice clinicians after standardized teaching sessions. METHODS: All
      students received a training session. In experiment 1, twenty canals of
      mandibular molars were prepared with GT and ProTaper rotaries by 10 students.
      Standardized radiographs were exposed before and after canal preparation, and
      canal curvature was measured; canals were assessed for patency and preparation
      time. In experiment 2, mandibular molars (20 canals) were submitted to
      microcomputed tomography before and after canal preparation with ProTaper and GT
      rotaries by 2 dental students. Canals were metrically assessed for changes
      (volume, surface, cross-sectional shape, transportation) during canal preparation
      by using software. RESULTS: In experiment 1, canal curvature decreased by 7.6
      degrees and 7.8 degrees for GT and ProTaper preparations; there were no broken
      instruments, and 2 canals lost patency. The time for GT preparation was longer
      than for ProTaper (29.7 +/- 6.8 vs 19.4 +/- 8.1 minutes, P <.05). In experiment
      2, canal volumes and surface areas increased (P < .001), and prepared canals were
      rounder in cross-section and more tapered. Mean canal transportation ranged
      between 0.14 +/- 0.05 mm and 0.23 +/- 0.09 mm for apical and coronal canal
      thirds. There were no significant differences between the instruments or the
      operators regarding center of mass shifts; qualitative and quantitative data for
      canal transportation were similar to earlier studies with experienced operators.
      CONCLUSIONS: Both rotary instruments performed adequately with inexperienced
      operators who received a brief structured training session.

PMID- 19840655
TI  - Evaluation of correspondence of dental Computed Tomography imaging to anatomic
      observation of external root resorption.
AB  - Radiography using a compact dental CT, the 3D Accuitomo XYZ Slice View Tomograph
      (3D Accuitomo), was performed for examining the root resorption of a mandibular
      premolar in a patient who needed endodontic therapy. The images obtained by the
      3D Accuitomo clearly showed the apparent presence of external root resorption of
      the tooth. As the root resorption had progressed seriously, the diagnosis was
      that it was impossible to save the tooth. After having obtained informed consent
      from the patient, the tooth was extracted. The surface of the root of the
      extracted tooth was examined visually without magnification, and the observations
      were compared with the findings made by 3D Accuitomo imaging for evaluating the
      reliability of the dental CT for diagnostic imaging of root resorption. The
      radiographic and visual examination results corresponded completely. Thus the 3D
      Accuitomo depicted the aspects of root resorption accurately; and its application
      for clinical use should be very effective for examining and diagnosing root
      resorption.

PMID- 19840656
TI  - Anterior Stafne's bone cavity mimicking a periapical lesion of endodontic origin:
      report of two cases.
AB  - INTRODUCTION: This report of 2 cases describes the diagnostic procedures used to
      identify 2 Stafne's bone cavities (SBC) found in unusually anterior locations in
      the mandible, both mimicking periapical lesions of endodontic origin. METHODS: In
      the first patient, a 47-year-old man, an SBC was diagnosed in the area of teeth
      #27, 28, and 29. In the second patient, a 62-year-old man, the SBC was a
      fortuitous finding, because this patient was referred for dental implant therapy.
      RESULTS: In both cases, the final diagnosis was achieved by using limited cone
      beam computed tomography (CBCT) and magnetic resonance imaging (MRI). In both
      patients, the lingual bone cavity was found to be occupied by accessory salivary
      gland tissue. CONCLUSIONS: The combination of CBCT and MRI as noninvasive
      diagnostic techniques seems ideal to avoid surgical explorations, incisional
      biopsies, or enucleations of the lesion for diagnostic purposes.

PMID- 19840657
TI  - Retreatment of a resected tooth associated with a large periradicular lesion by
      using a triple antibiotic paste and mineral trioxide aggregate: a case report
      with a thirty-month follow-up.
AB  - INTRODUCTION: Trauma to the teeth and supporting structures is a frequent problem
      among children. Endodontic treatment is necessary for 41.3% of traumatized teeth.
      Two of the most important criteria for successful endodontic treatment are the
      elimination of microorganisms and apical sealing. A combination of antibiotic
      drugs (metranidozole, ciprofloxacin, and minocycline) is used to eliminate target
      bacteria, which are possible sources of endodontic lesions. For cases in which
      apical sealing is difficult, specific materials to plug the apical region have
      been advocated. Mineral trioxide aggregate (MTA) has become the material of
      choice because it is biocompatible and has bacteriostatic action. METHODS: This
      case report describes the nonsurgical retreatment of a traumatized tooth that had
      already undergone unsuccessful apical resection associated with a large
      periradicular lesion. A combination of antibiotic drugs was used as an intracanal
      medicament, and MTA was used to obtain a hermetic seal of the lateral tooth that
      had undergone unsuccessful apical resection. RESULTS: On follow up, the tooth was
      clinically and radiographically asymptomatic for 30 months. CONCLUSIONS: The
      results of this case show that MTA and triple antibiotic paste can be used
      clinically in the treatment of an unsuccessfully resected tooth associated with a
      large periradicular lesion.

PMID- 19840659
TI  - Characterisation of influenza A viruses with mutations in segment 5 packaging
      signals.
AB  - Influenza A virus vRNA segments contain specific packaging signals at their
      termini that overlap the coding regions. To further characterise segment 5
      packaging signals, we introduced synonymous mutations into the terminal coding
      regions of the vRNA and characterised the replicative fitness of the resulting
      viruses. Most mutations tested were well-tolerated, but a virus with alterations
      to NP codons 464-466, near the 5'-end of the vRNA, produced small plaques and
      replicated to around one-tenth of the level of wild type virus. The mutant virus
      supported normal levels of NP and segment 5 vRNA synthesis but packaged reduced
      levels of both segment 5 and segment 3 into virus particles. This suggests an
      interaction between segments 3 and 5 during influenza A virus assembly.

PMID- 19840660
TI  - PolyI:polyC12U adjuvant-combined intranasal vaccine protects mice against highly
      pathogenic H5N1 influenza virus variants.
AB  - The highly pathogenic avian H5N1 influenza virus has the potential to incite a
      global pandemic. Therefore, there is an urgent need to develop effective vaccines
      against these viruses. Because it is difficult to predict which strain of
      influenza will cause a pandemic, it is advantageous to develop vaccines that will
      confer cross-protective immunity against variants of the influenza virus.
      Recently, we reported that the Toll-like receptor 3 agonist, polyI:polyC(12)U
      (Ampligen), has been proven to be safe in a Phase III human trial, and is an
      effective mucosal adjuvant for intranasal H5N1 influenza vaccination. Intranasal
      administration of an Ampligen adjuvanted pre-pandemic H5N1 vaccine (NIBRG14),
      which was derived from the A/Vietnam/1194/2004 strain, resulted in the secretion
      of vaccine-specific IgA and IgG in nasal mucosa and serum, respectively, and
      protected mice against homologous A/Vietnam/1194/2004 and heterologous A/Hong
      Kong/483/97 and A/Indonesia/6/2005 viral challenge.

PMID- 19840661
TI  - M2e-based universal influenza A vaccine.
AB  - Human influenza causes substantial morbidity and mortality. Currently, licensed
      influenza vaccines offer satisfactory protection if they match the infecting
      strain, but they come with significant drawbacks. These vaccines are derived from
      prototype viruses, containing the hemagglutinin of influenza viruses that are
      likely to cause the next epidemic. Their usefulness against a future pandemic,
      however, remains problematic. A vaccine based on the ectodomain of influenza
      matrix protein 2 (M2e) could overcome these drawbacks. M2e is highly conserved in
      both human and avian influenza A viruses. The low immunogenicity against natural
      M2e can be overcome by fusing M2e to an appropriate carrier such as Hepatitis B
      virus-derived virus-like particles. Such chimeric particles can be produced in a
      simple and safe bacterial expression system, requiring minimal biocontainment,
      and can be obtained in a pure form. Experiments in animal models have
      demonstrated that M2e-based vaccines induce protection against a lethal challenge
      with various influenza A virus subtypes. Furthermore, the production and use of
      an effective M2e-vaccine could be implemented at any time regardless of
      seasonality, both in an epidemic as well as in a pandemic preparedness program.
      In animal models, M2e-vaccines administered parenterally or intranasally protect
      against disease and mortality following challenge with various influenza A
      strains. Adjuvants suitable for human use improve protection, which correlates
      with higher anti-M2e antibody responses of defined subtypes. Recently, Phase I
      clinical studies with M2e-vaccines have been completed, indicating their safety
      and immunogenicity. Further clinical development of this universal influenza A
      vaccine candidate is being pursued in order to validate its protective efficacy
      in humans.

PMID- 19840662
TI  - MF59-adjuvanted influenza vaccine (FLUAD) in children: safety and immunogenicity
      following a second year seasonal vaccination.
AB  - After priming with two intramuscular doses of MF59-adjuvanted (Sub/MF59) or split
      influenza vaccines during the 2006/07 season, 89 healthy children received a
      third booster dose of the respective vaccine (2007/08 Northern Hemisphere
      formulation) approximately 1 year later, and were followed up for 6 months post
      third injection. Immunogenicity was evaluated on 81 of them by a hemagglutination
      inhibition (HI) assay before and 3 weeks after vaccination. The Sub/MF59
      influenza vaccine was safe and well tolerated following the booster vaccination.
      Pre-booster HI antibody titers were consistently higher in the Sub/MF59 group
      than in the comparator group, confirming significantly longer persistence of
      antibodies after priming with Sub/MF59 vaccine. Post-booster immune responses
      were significantly higher in the Sub/MF59 group compared with the split group,
      especially vs. the influenza B strain, which is epidemiologically relevant in the
      pediatric population. Altogether, these data further support the potential use of
      MF59-adjuvanted influenza vaccine as a safe and highly immunogenic influenza
      vaccine for young children.

PMID- 19840663
TI  - Preclinical evaluation of a modified vaccinia virus Ankara (MVA)-based vaccine
      against influenza A/H5N1 viruses.
AB  - Highly pathogenic avian influenza viruses of the H5N1 subtype are responsible for
      an increasing number of infections in humans since 2003. More than 60% of the
      infections is lethal and new infections are reported frequently. In the light of
      the pandemic threat caused by these events the rapid availability of safe and
      effective vaccines is desirable. Modified vaccinia virus Ankara (MVA) expressing
      the HA gene of an influenza A/H5N1 virus is a promising candidate vaccine that
      induced protective immunity against infection with homologous and heterologous
      influenza A/H5N1 viruses in mice. We also evaluated the recombinant MVA vector
      expressing the HA of influenza A/H5N1 virus A/Vietnam/1194/04 (MVA-HA-VN/04) in
      non-human primates. Cynomolgus macaques were immunized twice and then challenged
      with influenza virus A/Vietnam/1194/04 (clade 1) or A/Indonesia/5/05 (clade 2.1)
      to assess the level of protective immunity. Immunization with MVA-HA-VN/04
      induced (cross-reactive) antibodies and prevented virus replication in the upper
      and lower respiratory tract and the development of severe necrotizing
      bronchointerstitial pneumonia. Therefore MVA-HA-VN/04 is a promising vaccine
      candidate for the induction of protective immunity against highly pathogenic
      avian influenza A/H5N1 viruses.

PMID- 19840665
TI  - Challenges in evaluating influenza vaccine effectiveness and the mortality
      benefits controversy.
AB  - Randomized, controlled trials are the gold standard study design. However,
      ethical constraints and practical considerations may necessitate other types of
      studies for evaluating influenza vaccine effectiveness in the elderly--a high
      priority group for annual vaccination in many countries. Observational studies
      therefore comprise the bulk of the vaccine effectiveness evidence in older
      persons, but these types of studies can be susceptible to selection bias and
      residual confounding. All observational studies should utilize strategies to
      minimize the impact of bias and confounding. Recent studies questioning the
      plausibility of reported mortality benefits among vaccinated elderly persons may
      themselves be based on assumptions that are susceptible to important limitations
      and multiple biases. Future studies that incorporate prospectively collected
      information on functional status, life expectancy, and other types of data may
      provide additional insights into these concerns. At present, even after taking
      into account the potential for residual bias and confounding, most studies
      confirm the benefits of vaccination among the elderly for reducing
      hospitalization and death.

PMID- 19840664
TI  - Influenza vaccination and mortality benefits: new insights, new opportunities.
AB  - Influenza vaccination control strategies in most countries rely on vaccination of
      seniors and other high risk groups. Although placebo-controlled randomized trials
      show influenza vaccine is effective in younger age groups, few seniors >70 years
      were studied even though they suffer >90% of influenza-related deaths. Excess
      mortality studies could not confirm a national decline in influenza-related
      mortality while vaccine coverage quadrupled. Cohort studies have consistently
      reported that vaccination reduces all-cause winter mortality by approximately
      50%, an astonishing claim given only approximately 5% of all winter deaths are
      attributable to influenza. This VE overestimation has now been attributed to
      profound confounding frailty selection bias. A way forward includes a new
      generation of unbiased studies with laboratory endpoints, and requires an
      agreement that the evidence base was flawed. The latter may clear the way for
      more immunogenic vaccines for seniors and exploration of other influenza control
      strategies.

PMID- 19840666
TI  - Nuclear functions of the influenza A and B viruses NS1 proteins: do they play a
      role in viral mRNA export?
AB  - Although it is known for decades that influenza viruses replicate and transcribe
      their genome in the nucleus of the host cell, there is little knowledge about the
      cellular and viral factors mediating the nuclear transport of viral mRNA
      transcripts to the cytoplasm. Efficient export of mature cellular mRNA is coupled
      to their synthesis by the RNA polymerase II and subsequent processing events such
      as splicing. This linkage necessitated influenza viruses to evolve a strategy to
      integrate their unspliced mRNAs generated by the viral polymerase into a cellular
      mRNA export pathway. Recent findings suggest that the major cellular mRNA export
      receptor Tap/NXF1 promotes the influenza virus mRNA export. Here, we review
      functions of the NS1 proteins of influenza A and B viruses and discuss the
      emerging evidence supporting a role of these viral factors in the export of viral
      mRNAs.

PMID- 19840668
TI  - MDCK cells that express proteases TMPRSS2 and HAT provide a cell system to
      propagate influenza viruses in the absence of trypsin and to study cleavage of HA
      and its inhibition.
AB  - Cleavage of the influenza virus hemagglutinin (HA) by host cell proteases is
      essential for virus infectivity and, therefore, relevant proteases may present
      promising new drug targets. We recently demonstrated that serine proteases
      TMPRSS2 and HAT from human airways activate influenza virus HA with monobasic
      cleavage site in vitro. In the present study we generated MDCK cells with
      inducible expression of either TMPRSS2 or HAT. MDCK-TMPRSS2 and MDCK-HAT cells
      supported growth of human and avian influenza viruses of different subtypes in
      the absence of exogenous trypsin. Further, we used these cell lines to
      investigate the efficacy of protease inhibitors to prevent proteolytic activation
      of HA by TMPRSS2 and HAT. Multicycle viral replication in both cell lines was
      markedly suppressed in the presence of serine protease inhibitors and we found
      that particularly in MDCK-HAT cells proteolytic activation of progeny viruses was
      very susceptible to inhibitor treatment. Taken together, our data demonstrate
      that MDCK-HAT and MDCK-TMPRSS2 cells are useful experimental systems to study
      cleavage of HA by host cell protease and its inhibition and in addition represent
      applicable cell lines to propagate influenza viruses in the absence of trypsin.

PMID- 19840667
TI  - Structural basis for oseltamivir resistance of influenza viruses.
AB  - Oseltamivir, one of the two anti-neuraminidase drugs, is currently the most
      widely used drug against influenza. Resistance to the drug has occurred
      infrequently among different viruses in response to drug treatment, including A
      H5N1 viruses, but most notably has emerged among recently circulating A H1N1
      viruses and has spread throughout the population in the absence of drug use.
      Crystal structures of enzyme-drug complexes, together with enzymatic properties,
      of mutants of H5N1 neuraminidase have provided explanations for high level
      oseltamivir resistance due to the common H275Y mutation, with retention of
      zanamivir susceptibility, and intermediate level resistance due to the N295S
      mutation. Complementation of enhanced NA activity due to a D344N mutation by the
      H275Y mutation suggests an explanation for the recent emergence and predominance
      of oseltamivir-resistant influenza A H1N1 viruses.

PMID- 19840669
TI  - Prior infection with an H1N1 swine influenza virus partially protects pigs
      against a low pathogenic H5N1 avian influenza virus.
AB  - Most humans lack virus neutralizing (VN) and haemagglutination inhibition (HI)
      antibodies to H5N1 avian influenza viruses (AIVs), but cross-reactive
      neuraminidase inhibition (NI) antibodies and cell-mediated immune (CMI) responses
      are common. These immune responses result largely from infections with seasonal
      human H1N1 influenza viruses, but the protective effect of H1N1 infection
      immunity against H5N1 infection has never been examined. To this purpose, we have
      used the pig model of influenza and a low pathogenic (LP) H5N1 AIV. Pigs were
      inoculated intranasally with sw/Belgium/1/98 (H1N1) 4 weeks before challenge with
      duck/Minnesota/1525/81 (H5N1). While the viruses failed to cross-react in HI and
      VN tests, the H1N1 infection induced high levels of H5N1 cross-reactive NI
      antibodies. Cross-reactive CMI was demonstrated by measurements of
      lymphoproliferation and IFN-gamma secretion after in vitro restimulation of
      peripheral blood mononuclear cells. All control pigs showed clinical signs and
      H5N1 virus isolation from the respiratory tract post-challenge. The H1N1-immune
      pigs, in contrast, showed a complete clinical protection and only 3 pigs out of
      10 were H5N1 virus-positive. In a second and smaller experiment, H1N1 virus
      infection also conferred cross-protection against a LP H5N2 AIV, while cross
      reactive immunity was solely detected in tests for CMI. Our data further support
      the notion that immunity induced by seasonal human H1N1 influenza virus infection
      may provide some protection against H5N1 or other H5 AIVs in the absence of
      neutralizing H5 antibodies. Further studies should reveal whether cross
      protection holds against H5N1 viruses that are better adapted to replicate in
      mammals or with a more distantly related N1.

PMID- 19840670
TI  - Avian influenza virus: of virus and bird ecology.
AB  - The recent introductions of highly pathogenic avian influenza (HPAI) H5N1 virus
      in wild birds and its subsequent spread throughout Asia, the Middle East, Africa
      and Europe has put a focus on the role of wild birds in the geographical spread
      of HPAI H5N1 virus. Large-scale surveillance programs are ongoing to determine a
      potential role of wild birds in H5N1 virus spread and to serve as sentinel
      systems for introductions into new geographical regions. The unprecedented scale
      and coverage of these surveillance programs offer a unique opportunity to expand
      our current knowledge on the ecology of LPAI in wild migratory birds. We provide
      an update on the current knowledge on the relation between host and virus
      ecology.

PMID- 19840671
TI  - Poultry movement networks in Cambodia: implications for surveillance and control
      of highly pathogenic avian influenza (HPAI/H5N1).
AB  - Movement of poultry through markets is potentially important in the circulation
      and spread of highly pathogenic avian influenza. However little is understood
      about poultry market chains in Cambodia. We conducted a cross-sectional survey of
      715 rural villagers, 123 rural, peri-urban and urban market sellers and 139
      middlemen from six provinces and Phnom Penh, to evaluate live poultry movement
      and trading practices. Direct trade links with Thailand and Vietnam were
      identified via middlemen and market sellers. Most poultry movement occurs via
      middlemen into Phnom Penh making live bird wet markets in Phnom Penh a potential
      hub for the spread of H5N1 and ideal for surveillance and control.

PMID- 19840672
TI  - Internet-based monitoring of influenza-like illness in the general population:
      experience of five influenza seasons in The Netherlands.
AB  - Like in most other countries, influenza surveillance in The Netherlands is based
      upon influenza-like illness (ILI) consultations reported by sentinel general
      practitioners (GP). In addition, an internet-based monitoring of ILI in the
      general population started in 2003/2004 (Great Influenza Survey (GIS)). We
      compared GIS results over 5 influenza seasons with results from the GP system.
      Weekly ILI incidence from GIS correlated well with ILI incidence from the GP
      system the same week and even better 1 week later. This suggests that GIS is
      useful for early detection of trends in influenza activity. However, two
      important vulnerable groups, children and the elderly, are clearly
      underrepresented in the GIS. Furthermore, virological confirmation is lacking in
      the GIS. So, GIS can be a useful addition to the GP system, especially when
      representativeness can be improved and when participation remains at the current
      high level.

PMID- 19840674
TI  - Influenza virus CTL epitopes, remarkably conserved and remarkably variable.
AB  - Virus-specific cytotoxic T lymphocytes (CTL) contribute to the control of virus
      infections including those caused by influenza viruses. Especially under
      circumstances when antibodies induced by previous infection or vaccination fail
      to recognize and neutralize the virus adequately, CTL are important and
      contribute to protective immunity. During epidemic outbreaks caused by antigenic
      drift variants and during pandemic outbreaks of influenza, humoral immunity
      against influenza viruses is inadequate. Under these circumstances, pre-existing
      CTL directed to the relatively conserved internal proteins of the virus may
      provide cross-protective immunity. Indeed, most of the known human influenza
      virus CTL epitopes are conserved. However, during the evolution of influenza
      A/H3N2 viruses, the most important cause of seasonal influenza outbreaks,
      variation in CTL epitopes has been observed. The observed amino acid
      substitutions affected recognition by virus-specific CTL and the human virus
      specific CTL response in vitro. Examples of variable epitopes and their HLA
      restrictions are: NP(383-391)/HLA-B*2705, NP(380-388)/HLA-B*0801, NP(418-426)/HLA
      B*3501, NP(251-259)/HLA-B*4002, NP(103-111)/HLA-B*1503. In some cases amino acid
      substitutions occurred at anchor residues and in other cases at T cell receptor
      contact residues. It is of special interest that the R384G substitution in the
      NP(383-391) epitope was detrimental to virus fitness and was only tolerated in
      the presence of multiple functionally compensating co-mutations. In contrast,
      other epitopes, like the HLA-A*0201 restricted epitope from the matrix protein,
      M1(58-66), are highly conserved despite their immunodominant nature and the high
      prevalence of HLA-A*0201 in the population. A mutational analysis of this epitope
      indicated that it is under functional constraints. Also in influenza A viruses of
      other subtypes, including H5N1, the M1(58-66) is highly conserved.

PMID- 19840673
TI  - Antibody quantity versus quality after influenza vaccination.
AB  - The correlates for protection against influenza infection are incompletely
      characterized. We have applied an ELISA strategy that distinguishes antibodies
      against native viral surface antigens (potentially neutralizing) from antibodies
      directed against internal and denatured viral proteins (not neutralizing) to
      three groups of vaccinated subjects: (1) participants in a study of repeated
      annual vaccination, (2) elderly subjects and (3) patients with Systemic Lupus
      Erythematosus compared to control subjects. Antibody increase after vaccination
      was inversely related to the level of pre-existing antibodies in all groups; most
      subjects had significant initial antibody levels and showed little increase in
      amount of antibody after vaccination, but the avidity of their serum antibodies
      tended to increase. Antibodies against denatured virus proteins varied with
      vaccine formulation; vaccines that are more recent have less total protein for
      the same amount of native hemagglutinin. We propose an index consisting of rank
      order of antibody level plus antibody avidity, both measured against native
      virus, plus hemagglutination-inhibition antibody titer, as a useful measure of
      immunity against influenza.

PMID- 19840675
TI  - WHO meeting on the role of neuraminidase in inducing protective immunity against
      influenza infection, Vilamoura, Portugal, September 14, 2008.

PMID- 19840676
TI  - Point-of-care testing. Preface.

PMID- 19840677
TI  - Point-of-care testing: an overview and a look to the future (circa 2009, United
      States).
AB  - Point-of-care testing is a rapidly growing area in laboratory medicine.
      Technologies related to point-of-care testing have unique analytical features and
      are used in a number of clinical applications. These attributes combined with
      complex regulatory requirements have made point-of-care testing a true specialty
      within pathology. Manufacturers continue to develop new point-of-care tests and
      have consolidated multiple assays to single small handheld or bench-top devices.
      Enterprise hospital-wide data management systems are available to facilitate
      improved regulatory compliance and transmit test results into the electronic
      medical record. Some studies have shown that point-of-care testing can improve
      clinical outcomes or increase the efficiency of hospital operations. In spite of
      these developments, many challenges remain. In some cases, the quality of point
      of-care tests performed by nonlaboratory personnel does not match that of testing
      performed in the central laboratory. Data management connectivity remains a
      significant problem, especially for manually performed tests. Managing a point-of
      care program to maintain regulatory compliance is also problematic. For these
      reasons, the future of point-of-care testing is not entirely clear. The most
      likely scenario will be a slow but progressive growth of point-of-care testing in
      the hospital, in the outpatient clinic, and in the home.

PMID- 19840678
TI  - Management of a point-of-care testing program.
AB  - The approach to managing a point-of-care testing (POCT) program has evolved over
      recent years. Although many of the essential features of early POCT management
      programs remain intact, contemporary challenges including expansion of the test
      menu, changing regulatory requirements, and the development of more sophisticated
      data management connectivity require ongoing adaptation of POCT management
      programs. Despite improvements in test quality and regulatory compliance,
      significant challenges for the management of POCT will continue for the
      foreseeable future.

PMID- 19840679
TI  - Point-of-care testing informatics.
AB  - Managing patient test data and documenting regulatory compliance for tests
      performed at the point of care have traditionally been significant problems. In
      many situations, manual record-keeping has proven entirely inadequate for
      maintaining the integrity of the patient medical record or for providing an audit
      trail for quality assurance activities. Starting in the 1990s, a number of
      companies began to develop and market point-of-care data management systems. Over
      time, these data management systems have become increasingly sophisticated. It is
      now possible to interface multiple point-of-care devices from different
      manufacturers to a central data manager that is bidirectionally interfaced to the
      laboratory and hospital information systems. Despite these advances, many
      challenges remain. True real-time point-of-care "connectivity" across an entire
      institution has yet to be achieved, and there is still no satisfactory solution
      for manually performed visually read tests, some of which are commonly performed
      at the point of care. In the future, wireless point-of-care connectivity
      solutions hold great promise, but these technologies are yet to be fully
      developed.

PMID- 19840680
TI  - Regulatory compliance for point-of-care testing: 2009 United States perspective.
AB  - All clinical laboratory testing in the United States is regulated by the Clinical
      Laboratory Improvement Amendments of 1988 (CLIA'88 or CLIA) and overseen by the
      Centers for Medicare and Medicaid Services. CLIA profoundly changed the
      prevailing United States regulatory philosophy by imposing uniform requirements
      for all clinical laboratory testing regardless of where tests are performed. In
      the hospital, regulatory compliance is usually ensured by regular inspections of
      the laboratory by either the Joint Commission or by the College of American
      Pathologists. These organizations may include requirements beyond the minimum
      standard mandated by CLIA. This article reviews the status of regulatory
      compliance of point-of-care testing from a perspective of the current regulations
      in effect in the United States in 2009.

PMID- 19840681
TI  - Perspectives on cost and outcomes for point-of-care testing.
AB  - Point-of-care testing (POCT) is usually more expensive on a unit-cost basis than
      testing performed in a central laboratory. It is difficult to manage POCT and to
      maintain regulatory compliance, especially in large institutions. However, some
      POCT technologies have improved patient outcomes (patient self-glucose monitoring
      in the home, tight glycemic control in intensive care settings) or hospital or
      emergency department operations (whole-blood cardiac-marker testing and D-dimer
      testing in emergency departments). In some cases, these outcomes result simply
      from making a new test available, rather than performing the test at the point of
      care. In most cases, the rapid turnaround time provided by POCT is the main
      factor that is ultimately responsible for the improvement in outcomes.

PMID- 19840682
TI  - HIV testing near the patient: changing the face of HIV testing.
AB  - Virological, epidemiologic, and operational barriers have slowed the progress
      toward effective management and eradication of HIV infection, despite significant
      advances in diagnosis since the early 1980s. Because early diagnosis profoundly
      affects the health care and survival of infected/high-risk individuals, and
      because the time required for conventional testing remains a barrier in many
      settings, rapid HIV testing has been developed for use both in the clinical
      laboratory and at the point of care. Recent studies have identified applications,
      advantages, and limitations of these assays, which may influence the development
      of new and more effective public health testing and screening protocols. In the
      United States, the Food and Drug Administration has approved the use of six rapid
      HIV tests. This review summarizes these modern rapid point-of-care HIV tests and
      their role in preventing the spread of HIV and in detecting, managing, and
      treating patients affected by the HIV pandemic.

PMID- 19840683
TI  - Drug-of-abuse testing at the point of care.
AB  - Sensitive and specific assays are available to detect drugs of abuse at the point
      of care. This article describes the characteristics of point-of-care devices for
      drug-of-abuse testing with a focus on clinical utility and patient care. This
      article is not a comprehensive review of all available point-of-care devices.
      Instead, it discusses general principles of point-of-care testing for drugs of
      abuse.

PMID- 19840684
TI  - Tight glycemic control and point-of-care testing.
AB  - Until recently, inpatient glycemic management focused solely on the diabetic
      patient with few reported studies that discussed hyperglycemic management of the
      nondiabetic patient. For the last 35 years, the prevailing notion was that
      hyperglycemia in the acutely ill nondiabetic inpatient was a consequence of
      illnesses as well as a marker of its severity. It was also thought to be an
      adaptive response to injury necessary for survival and not necessarily a
      prognostic indicator of morbidity or mortality. In this article, we discuss the
      current school of thought regarding prognostic implications of nondiabetic
      inpatient hyperglycemia, its management (tight glycemic control), and the
      relationship of point-of-care testing to tight glycemic control.

PMID- 19840685
TI  - Fecal occult blood testing.
AB  - Colorectal cancer (CRC) is the third most common cancer in the United States. A
      reduction in cumulative mortality occurs when patients are routinely screened by
      fecal occult blood tests (FOBT) and early lesions are removed. These point-of
      care tests detect minute amounts of blood released from precancerous and
      cancerous colon lesions. Positive test results should be followed up with
      complete diagnostic testing to treat precancerous lesions and diagnose patients
      at earlier stages of cancer, thereby increasing overall survival. More complex
      assays are designed to detect genetic changes in cells released from malignant
      and even premalignant lesions. This article provides information on the screening
      and diagnostic tests available for CRC detection as well as the advantages and
      disadvantages of each.

PMID- 19840686
TI  - Point-of-care testing in coagulation.
AB  - Point-of-care (POC) assays are available for a variety of coagulation tests.
      These assays are generally simple to perform and have a more rapid turnaround
      time than their central-laboratory counterparts. This article discusses the
      current status of coagulation POC methodologies, focusing on the potential
      clinical uses and the limitations of platelet function testing, prothrombin
      time/international normalized ratio, D-dimer, and activated clotting time (ACT).
      Additional studies are eagerly awaited regarding potential future uses of POC
      coagulation testing, including the role of platelet function testing and ACT
      heparin management systems.

PMID- 19840687
TI  - Point-of-care testing and molecular diagnostics: miniaturization required.
AB  - Turnaround time for molecular diagnostic tests is critical in detecting
      infectious agents, in determining a patient's ability to metabolize a drug or
      drug class, and in detecting minimal residual disease. These applications would
      benefit from the development of a point-of-care device for nucleic acid
      extraction, amplification, and detection. The ideal device would have a low cost
      per test, use a disposable unit use device for all steps in the assay, be
      portable, and provide a result that requires no interpretation. The creation of
      such a device requires miniaturization of current technologies and the use of
      microfluidics, microarrays, and small-diameter capillary tubes to reduce reagent
      volumes and simplify heat conduction by convection during nucleic acid
      amplification. This ideal device may be available in 3 to 5 years and will
      revolutionize and expand the global availability of molecular diagnostic assays.

PMID- 19840688
TI  - Point-of-care testing for cardiac markers in acute coronary syndromes and heart
      failure.
AB  - Advances in technologies for immunoassay testing have enabled the development of
      15-minute whole-blood assays for cardiac markers in the evaluation of patients
      with acute coronary syndromes (ACS) and congestive heart failure. In many cases,
      the analytical performance of these assays is equivalent to that of testing in
      the central laboratory. Rapid whole-blood point-of-care assays for troponin,
      creatine kinase isoenzyme CK-MB, myoglobin, and B-type natriuretic peptides have
      facilitated efforts to restructure conventional approaches to ACS and heart
      failure in the emergency room. Improvements in outcomes, including decreased
      emergency room and hospital length-of-stay, decreased overall cost, and earlier
      discharge of low-risk patients, have been documented following implementation of
      these technologies.

PMID- 19840689
TI  - Provider-performed microscopy.
AB  - Point-of-care testing (POCT) is defined as analytic testing performed outside the
      central laboratory using a device or devices that can be easily transported to
      the vicinity of the patient. This article discusses rules and regulations
      concerning POCT, especially those covering provider-performed microscopy (PPM).
      Types of PPM are also covered, including the fern test, tests for the presence on
      fecal leukocytes and pinworms, and examinations of urine sediment and seminal
      fluid. The coordination of PPM within a hospital is also covered.

PMID- 19840690
TI  - Point-of-care testing for disasters: needs assessment, strategic planning, and
      future design.
AB  - Objective evidence-based national surveys serve as a first step in identifying
      suitable point-of-care device designs, effective test clusters, and environmental
      operating conditions. Preliminary survey results show the need for point-of-care
      testing (POCT) devices using test clusters that specifically detect pathogens
      found in disaster scenarios. Hurricane Katrina, the tsunami in southeast Asia,
      and the current influenza pandemic (H1N1, "swine flu") vividly illustrate lack of
      national and global preparedness. Gap analysis of current POCT devices versus
      survey results reveals how POCT needs can be fulfilled. Future thinking will help
      avoid the worst consequences of disasters on the horizon, such as extensively
      drug-resistant tuberculosis and pandemic influenzas. A global effort must be made
      to improve POC technologies to rapidly diagnose and treat patients to improve
      triaging, on-site decision making, and, ultimately, economic and medical
      outcomes.

PMID- 19840691
TI  - Selected topics in point-of-care testing: whole blood creatinine, influenza
      testing, fetal fibronectin and patient self-testing in the home.
AB  - This article reviews selected topics in point-of-care testing including: whole
      blood creatinine testing, influenza testing, fetal fibronectin, and patient self
      testing. Each of these topics reflects an important new application of point-of
      care testing and together they illustrate the many niche applications for these
      technologies.

PMID- 19840692
TI  - Oseltamivir for influenza postexposure prophylaxis: economic evaluation for
      children aged 1-12 years in the U.S.
AB  - BACKGROUND: Postexposure prophylaxis (PEP) with oseltamivir (Tamiflu) has been
      shown to be effective and is approved in children exposed to a case of influenza
      in a household setting. Given limited healthcare budgets, it is important to
      understand the costs and cost effectiveness of PEP in children. PURPOSE: This
      study aims to estimate the cost effectiveness of oseltamivir PEP for children
      aged 1-12 years in the U.S. METHODS: A decision-tree model with a 1-year time
      horizon was used to assess the cost effectiveness of oseltamivir PEP for 10 days
      at approved doses compared with no prophylaxis for children aged 1-12 years who
      were exposed to a household index case of influenza from the U.S. societal and
      payer perspectives. Model inputs included U.S. influenza epidemiology data,
      efficacy data from oseltamivir PEP clinical trials, direct medical resource use
      and costs for PEP and influenza treatment derived from large U.S. databases, and
      indirect costs based on caregiver lost productivity. Base-case estimates were
      tested in extensive sensitivity analyses. RESULTS: For the societal perspective,
      the model estimated 12,184 fewer cases of influenza per 100,000 children exposed
      and an incremental cost-effectiveness ratio of $41,452 per quality-adjusted life
      year (QALY) gained. Results were most sensitive to the influenza attack rate, PEP
      protective efficacy, and prescribing patterns for initiating PEP. Probabilistic
      sensitivity analyses showed that oseltamivir PEP was likely to be cost effective
      for all willingness-to-pay threshold values above $34,300 per QALY gained.
      Results were similar for the payer perspective. CONCLUSIONS: Although there is no
      official cost-effectiveness threshold in the U.S., results from the current study
      show that when compared with no prophylaxis, oseltamivir PEP for children has
      cost-effectiveness ratios similar to those of vaccines for preventing influenza.

PMID- 19840693
TI  - Adverse childhood experiences and the risk of premature mortality.
AB  - BACKGROUND: Strong, graded relationships between exposure to childhood traumatic
      stressors and numerous negative health behaviors and outcomes, healthcare
      utilization, and overall health status inspired the question of whether these
      adverse childhood experiences (ACEs) are associated with premature death during
      adulthood. PURPOSE: This study aims to determine whether ACEs are associated with
      an increased risk of premature death during adulthood. METHODS: Baseline survey
      data on health behaviors, health status, and exposure to ACEs were collected from
      17,337 adults aged >18 years during 1995-1997. The ACEs included abuse
      (emotional, physical, sexual); witnessing domestic violence; parental separation
      or divorce; and growing up in a household where members were mentally ill,
      substance abusers, or sent to prison. The ACE score (an integer count of the
      eight categories of ACEs) was used as a measure of cumulative exposure to
      traumatic stress during childhood. Deaths were identified during follow-up
      assessments (between baseline appointment date and December 31, 2006) using
      mortality records obtained from a search of the National Death Index. Expected
      years of life lost (YLL) and years of potential life lost (YPLL) were computed
      using standard methods. The relative risk of death from all causes at age < or
      =65 years and at age < or =75 years was estimated across the number of categories
      of ACEs using multivariable-adjusted Cox proportional hazards regression.
      Analysis was conducted during January-February 2009. RESULTS: Overall, 1539
      people died during follow-up; the crude death rate was 91.0 per 1000; the age
      adjusted rate was 54.7 per 1000. People with six or more ACEs died nearly 20
      years earlier on average than those without ACEs (60.6 years, 95% CI=56.2, 65.1,
      vs 79.1 years, 95% CI=78.4, 79.9). Average YLL per death was nearly three times
      greater among people with six or more ACEs (25.2 years) than those without ACEs
      (9.2 years). Roughly one third (n=526) of those who died during follow-up were
      aged < or =75 years at the time of death, accounting for 4792 YPLL. After
      multivariable adjustment, adults with six or more ACEs were 1.7 (95% CI=1.06,
      2.83) times more likely to die when aged < or =75 years and 2.4 (95% CI=1.30,
      4.39) times more likely to die when aged < or =65 years. CONCLUSIONS: ACEs are
      associated with an increased risk of premature death, although a graded increase
      in the risk of premature death was not observed across the number of categories
      of ACEs. The increase in risk was only partly explained by documented ACE-related
      health and social problems, suggesting other possible mechanisms by which ACEs
      may contribute to premature death.

PMID- 19840694
TI  - Land use, residential density, and walking. The multi-ethnic study of
      atherosclerosis.
AB  - BACKGROUND: The neighborhood environment may play a role in encouraging sedentary
      patterns, especially for middle-aged and older adults. PURPOSE: The aim of this
      study was to examine the associations between walking and neighborhood population
      density, retail availability, and land-use distribution using data from a cohort
      of adults aged 45 to 84 years. METHODS: Data from a multi-ethnic sample of 5529
      adult residents of Baltimore MD, Chicago IL, Forsyth County NC, Los Angeles CA,
      New York NY, and St. Paul MN enrolled in the Multi-Ethnic Study of
      Atherosclerosis in 2000-2002 were linked to secondary land-use and population
      data. Participant reports of access to destinations and stores and objective
      measures of the percentage of land area in parcels devoted to retail land uses,
      the population divided by land area in parcels, and the mixture of uses for areas
      within 200 m of each participant's residence were examined. Multinomial logistic
      regression was used to investigate associations of self-reported and objective
      neighborhood characteristics with walking. All analyses were conducted in 2008
      and 2009. RESULTS: After adjustment for individual-level characteristics and
      neighborhood connectivity, it was found that higher density, greater land area
      devoted to retail uses, and self-reported proximity of destinations and ease of
      walking to places were each related to walking. In models including all land-use
      measures, population density was positively associated with walking to places and
      with walking for exercise for more than 90 minutes/week, both relative to no
      walking. Availability of retail was associated with walking to places relative to
      not walking, and having a more proportional mix of land uses was associated with
      walking for exercise for more than 90 minutes/week, while self-reported ease of
      access to places was related to higher levels of exercise walking, both relative
      to not walking. CONCLUSIONS: Residential density and the presence of retail uses
      are related to various walking behaviors. Efforts to increase walking may benefit
      from attention to the intensity and type of land development.

PMID- 19840695
TI  - Efficacy of two tailored interventions promoting physical activity in older
      adults.
AB  - BACKGROUND: Important health benefits can be obtained if effective low-cost
      interventions promoting physical activity, especially among older adults, are
      developed. DESIGN: This RCT investigated the efficacy of two tailored physical
      activity interventions in promoting awareness, initiation, and maintenance of
      physical activity among older adults compared to a wait-list control group. Data
      were collected in 2007. Analyses were conducted in 2008. SETTING/PARTICIPANTS: In
      total, 1971 Dutch older adults (mean age=64 years, 57% women) participated.
      INTERVENTION: Two tailored physical activity interventions, consisting of three
      tailored letters delivered during 4 months, were systematically developed. The
      basic tailored intervention targeted psychosocial determinants alone, while the
      environmentally tailored intervention (intervention-plus) additionally targeted
      environmental determinants. MAIN OUTCOME MEASURES: Awareness of personal physical
      activity behavior, self-reported level of physical activity, and compliance with
      the physical activity guideline were assessed at baseline, 3 months, and 6
      months. RESULTS: Intervention participants became more aware of their personal
      physical activity level at 6 months (OR(Ibasic)=1.7, OR(Iplus)=1.6) and were
      significantly more physically active at 3 (EffectSize[ES](Ibasic)=0.20,
      ES(Iplus)=0.20) and 6 months (ES(Ibasic)=0.30, ES(Iplus)=0.35) when compared to
      control participants. Moderation analyses showed that the interventions enhanced
      physical activity initiation at 3 (ES(Ibasic)=0.26, ES(Iplus)=0.21) and 6 months
      (ES(Ibasic)=0.32, ES(Iplus)=0.27) among participants insufficiently active at
      baseline, and induced maintenance at 6 months among participants sufficiently
      active at baseline (ES(Ibasic)=0.33, ES(Iplus)=0.34) when compared to the control
      condition. No differences between the intervention arms were found. CONCLUSIONS:
      The results indicate that tailoring can be an effective tool in attaining and
      enhancing awareness, initiation, and maintenance of physical activity among older
      adults. Targeting environmental determinants in addition to psychosocial
      determinants, however, did not result in an additional increase in physical
      activity behavior. TRIAL REGISTRATION: This study was registered with the Dutch
      Trial Register NTR 920.

PMID- 19840696
TI  - School-based interventions on childhood obesity: a meta-analysis.
AB  - BACKGROUND: Over the past decade, childhood obesity has been recognized as an
      increasing health problem worldwide. It is a predictor of obesity during
      adulthood, which is strongly linked to chronic lifestyle diseases. PURPOSE: This
      paper aims to evaluate the effectiveness of school-based programs in the
      prevention and management of childhood obesity. METHODS: A comprehensive
      literature search was undertaken for RCTs and clinical controlled trials on
      school-based interventions that addressed childhood obesity, published between
      1995 and 2007. The papers included for the meta-analysis were those in which ORs
      or standardized mean differences and their 95% CIs were reported or could be
      calculated from available data. RESULTS: Meta-analysis showed that the odds of
      participants' being overweight and obese in the school-based intervention
      programs compared with the control arm were significantly protective in the short
      term (OR=0.74, 95% CI=0.60, 0.92). Interventions that were conducted for more
      than 1 year had a higher OR of decreasing the prevalence of obesity. However,
      intervention programs were not effective in decreasing BMI compared with control
      treatments, with a weighted mean difference of -0.62 (95% CI=-1.39, 0.14).
      CONCLUSIONS: This meta-analysis showed that there was convincing evidence that
      school-based interventions are effective, at least short-term, in reducing the
      prevalence of childhood obesity. Longer-running programs were more effective than
      shorter programs.

PMID- 19840697
TI  - Urban sprawl and delayed ambulance arrival in the U.S.
AB  - BACKGROUND: Minimizing emergency medical service (EMS) response time is a central
      objective of prehospital care, yet the potential influence of built environment
      features such as urban sprawl on EMS system performance is often not considered.
      PURPOSE: This study measures the association between urban sprawl and EMS
      response time to test the hypothesis that features of sprawling development
      increase the probability of delayed ambulance arrival. METHODS: In 2008, EMS
      response times for 43,424 motor-vehicle crashes were obtained from the Fatal
      Analysis Reporting System, a national census of crashes involving > or =1
      fatality. Sprawl at each crash location was measured using a continuous county
      level index previously developed by Ewing et al. The association between sprawl
      and the probability of a delayed ambulance arrival (> or =8 minutes) was then
      measured using generalized linear mixed modeling to account for correlation among
      crashes from the same county. RESULTS: Urban sprawl is significantly associated
      with increased EMS response time and a higher probability of delayed ambulance
      arrival (p=0.03). This probability increases quadratically as the severity of
      sprawl increases while controlling for nighttime crash occurrence, road
      conditions, and presence of construction. For example, in sprawling counties
      (e.g., Fayette County GA), the probability of a delayed ambulance arrival for
      daytime crashes in dry conditions without construction was 69% (95% CI=66%, 72%)
      compared with 31% (95% CI=28%, 35%) in counties with prominent smart-growth
      characteristics (e.g., Delaware County PA). CONCLUSIONS: Urban sprawl is
      significantly associated with increased EMS response time and a higher
      probability of delayed ambulance arrival following motor-vehicle crashes in the
      U.S. The results of this study suggest that promotion of community design and
      development that follows smart-growth principles and regulates urban sprawl may
      improve EMS performance and reliability.

PMID- 19840698
TI  - Injuries due to falls from hunters' tree stands in Pennsylvania.
AB  - BACKGROUND: People who hunt deer from elevated tree stands may improve the
      chances of a successful hunt but also risk serious injury from a fall to the
      ground. PURPOSE: The objective of the current investigation is to estimate the
      rates of injuries from falls from tree stands using a population-based study
      design. METHODS: Annual and age-specific rates were calculated using injury data
      collected from 1987 to 2006 from all accredited Pennsylvania trauma centers and
      hunting license sales and game-take mail surveys from the Pennsylvania Game
      Commission. RESULTS: From 1987 through 2006, 2.73 people (n=499) per 100,000
      licensed deer hunters were injured from falls from tree stands; seven people
      died. Rates increased from 0.59 in 1987 to 7.08 in 2006 (p<0.001). Rates
      increased with age (p<0.001) and were highest among hunters aged 40-49 years. The
      case-fatality rate was 1.4%. CONCLUSIONS: Falls from tree stands associated with
      deer hunting are an increasing and important cause of injuries, especially for
      older hunters. Surveillance for tree stand-related injuries should be enhanced
      and preventive initiatives developed and tested.

PMID- 19840699
TI  - Longitudinal study of household smoking ban adoption among Korean Americans.
AB  - BACKGROUND: Few longitudinal studies have examined the adoption of bans on
      smoking in private homes. PURPOSE: This longitudinal study examined: (1) the
      prevalence of home smoking bans at baseline, (2) the incidence and predictors of
      new ban implementation by follow-up, and (3) the reasons for banning smoking and
      the difficulties with enforcement. METHODS: The sample consisted of 1360 adults
      of Korean descent residing in California who were interviewed by telephone (in
      English/Korean) at baseline during 2001-2002 and re-interviewed in 2006-2007.
      Data analyses were conducted in 2007-2008. RESULTS: The proportion of respondents
      with a complete household smoking ban grew from 59% at baseline to 91% by the
      follow-up interview. Among the 552 respondents who did not have a ban at
      baseline, 84% had adopted a ban by follow-up. Three baseline factors
      independently predicted ban adoption during the follow-up period: the presence of
      a nonsmoking respondent or spouse, the presence of nonsmoking family members, and
      respondent's belief that secondhand smoke caused lung cancer. The most highly
      rated reasons for banning smoking were as follows: because smoke annoys others,
      to protect family members, to avoid the odor, to discourage youth from smoking,
      and to encourage smokers to quit. Finally, respondents indicated that they would
      find it most difficult to ask their parent-in-law not to smoke. CONCLUSIONS: The
      proportion of households with smoking bans increased substantially, but
      households with smokers or family members who smoke remained less likely to
      implement bans. The importance of culturally sensitive programs to promote
      household bans cannot be overstated.

PMID- 19840700
TI  - Sensitivity of self-report mammography use in older women.
AB  - BACKGROUND: Recent survey evidence indicates a decline in mammography use among
      older women. PURPOSE: The objective of this study was to detect sensitivity of
      self-reported mammography use and pose evidence-based suggestions to increase
      survey accuracy. METHODS: Using the 1991-2006 Medicare Current Beneficiary
      Survey, 15,357 women, aged > or =65 years, were selected based on use of
      mammography services. The women were interviewed in the community setting at
      random periods after screening and asked, Have you had a mammogram or breast X
      ray since [today's date or previous supplement round interview date] a year ago?
      Statistical analyses were conducted between March 11 and April 28 of 2008. This
      study tested whether sensitivity (i.e., probability of an affirmative response)
      was dependent on length of the recall period and on respondent demographic and
      socioeconomic characteristics. RESULTS: Overall, 90.4% of the older women self
      reported use; however, sensitivity decreased as the recall period lengthened (90%
      at 6 months, 80% at 12 months). This time effect was significantly higher among
      older, economically disadvantaged women. Sensitivity also decreased an additional
      13.8% if the event occurred in the previous calendar year, and 3.5% if conducted
      in a non-English language or by proxy. CONCLUSIONS: Greatest sensitivity occurred
      during the 6-month period after service without straddling calendar years. These
      findings may aid the tailoring of future surveys for older adults, improving the
      recall of preventive services.

PMID- 19840701
TI  - Clinical preventive services for adolescents.
AB  - CONTEXT: Most of the many clinical preventive services (CPS) recommended for
      adolescents by various national organizations lack good evidence of
      effectiveness. Improving adolescent preventive care will require focusing on
      those CPS for which there is such evidence and on developing better delivery
      strategies. The objective of the current study was to identify those CPS for
      adolescents that do have a strong evidence base, to update the literature review
      and summarize evidence gaps where research is needed, and to summarize current
      delivery prevalence and opportunities. EVIDENCE ACQUISITION: A summary was
      conducted of the recommendations for adolescents of the U.S. Preventive Services
      Task Force (USPSTF) and the CDC's Advisory Committee on Immunization Practices
      (ACIP). An update is provided of the literature review for services with an
      inadequate evidence base to support a recommendation. A summary was prepared of
      the types of evidence still needed. A literature search was also conducted for
      current delivery prevalence of recommended services for those aged 11-17 years,
      and common gaps in the evidence were identified. EVIDENCE SYNTHESIS: Although 24
      CPS for adolescents have been reviewed by the USPSTF, only ten received definite
      recommendations and only seven of these favored delivery of the service. In
      addition, the ACIP recommends four immunizations for all adolescents, and two
      additional ones for those at high risk. There are many gaps in the evidence
      supporting most of the other services as well as in the information about current
      delivery prevalence. CONCLUSIONS: There are too many CPS recommended for
      adolescents with insufficient evidence of effectiveness, and there is low
      delivery prevalence for the few services with good evidence of effectiveness.
      Both more research and more attention to the practice changes that might improve
      delivery prevalence are needed.

PMID- 19840702
TI  - Neighborhood environment in studies of health of older adults: a systematic
      review.
AB  - CONTEXT: Epidemiologists and public health researchers are studying
      neighborhood's effect on individual health. The health of older adults may be
      more influenced by their neighborhoods as a result of decreased mobility.
      However, research on neighborhood's influence on older adults' health,
      specifically, is limited. EVIDENCE ACQUISITION: Recent studies on neighborhood
      and health for older adults were identified. Studies were identified through
      searches of databases including PsycINFO, CINAHL, PubMed, Academic Search
      Premier, Ageline, Social Science Citation Index, and Health Source. Criteria for
      inclusion were as follows: human studies; English language; study sample included
      adults aged > or =55 years; health outcomes, including mental health, health
      behaviors, morbidity, and mortality; neighborhood as the primary exposure
      variable of interest; empirical research; and studies that included > or =10
      neighborhoods. Air pollution studies were excluded. Five hundred thirty-eight
      relevant articles were published during 1997-2007; a total of 33 of these
      articles met inclusion criteria. EVIDENCE SYNTHESIS: The measures of objective
      and perceived aspects of neighborhood were summarized. Neighborhood was primarily
      operationalized using census-defined boundaries. Measures of neighborhood were
      principally derived from objective sources of data; eight studies assessed
      perceived neighborhood alone or in combination with objective measures. Six
      categories of neighborhood characteristics were socioeconomic composition, racial
      composition, demographics, perceived resources and/or problems, physical
      environment, and social environment. The studies are primarily cross-sectional
      and use administrative data to characterize neighborhood. CONCLUSIONS: These
      studies suggest that neighborhood environment is important for older adults'
      health and functioning.

PMID- 19840703
TI  - Clinical and translational science awards and community engagement: now is the
      time to mainstream prevention into the nation's health research agenda.
AB  - Although much attention is devoted to the slow process of cutting-edge "bench
      science" finding its way to clinical translation, less attention is paid to the
      fact that basic prevention messages, tests, and interventions never find their
      way into communities. The NIH Clinical & Translational Science Awards program
      seeks to address a broad mission of improving health, including both speeding up
      the incorporation of basic science discoveries throughout the clinical research
      pipeline and incorporating concerns of communities and practices into research
      agendas. The preventive medicine community now has an important opportunity to
      marry their mission of promoting and expanding prevention in communities to the
      nation's medical research agenda. This article suggests opportunities for
      collaboration.

PMID- 19840704
TI  - Ending the epidemic of heterosexual HIV transmission among African Americans.
AB  - This article examines factors responsible for the stark racial disparities in HIV
      infection in the U.S. and the now concentrated epidemic among African Americans.
      Sexual network patterns characterized by concurrency and mixing among different
      subpopulations, together with high rates of other sexually transmitted
      infections, facilitate dissemination of HIV among African Americans. The social
      and economic environment in which many African Americans live shapes sexual
      network patterns and increases personal infection risk almost independently of
      personal behavior. The African-American HIV epidemic constitutes a national
      crisis whose successful resolution will require modifying the social and economic
      systems, structures, and processes that facilitate HIV transmission in this
      population.

PMID- 19840705
TI  - Reducing low birth weight through home visitation.

PMID- 19840707
TI  - Saved by the carbon monoxide alarm.

PMID- 19840708
TI  - Obesity in critically ill patients. Preface.

PMID- 19840709
TI  - Cardiovascular effects of obesity: implications for critical care.
AB  - Obesity has become a global health crisis. The effects of obesity on the
      cardiovascular system pose a unique challenge for the critical care nurse. This
      article reviews the scope of the problem, the alterations in the cardiovascular
      structures and function, and the implications for critical care nursing.

PMID- 19840710
TI  - Pulmonary aspects of obesity in critical care.
AB  - Critically ill obese patients have many challenging pulmonary problems. The first
      key is to understand pathophysiology in the pulmonary system related to obesity.
      Second, it is important to identify the altered physical assessments and
      diagnostics that occur because of the pulmonary pathophysiology of obesity.
      Lastly, one should be aware of medical and nursing intervention options that
      treat symptoms or pulmonary problems of obesity. This article summarizes
      pulmonary issues related to obesity in critical care.

PMID- 19840712
TI  - Pain management in critically ill obese patients.
AB  - Achieving pain control in critically ill patients is a challenging problem for
      the health care team, which becomes more challenging in morbidly obese patients.
      Obese patients may experience drug malabsorption and distribution, which may lead
      to either subtherapeutic or toxic drug levels. To manage pain effectively for the
      critically ill obese patient, nurses must have an understanding of how obesity
      alters a patient's physiologic response to injury and illness. In addition,
      nurses must be knowledgeable about physiologic pain mechanisms, types and
      manifestations of pain, differing patterns of drug absorption and distribution,
      pharmacokinetic properties of analgesic medications, and pain management
      strategies. This article explores factors affecting pharmacokinetics in obese
      patients, trends in pain management, and treatment strategies for the obese
      patient.

PMID- 19840711
TI  - Skin integrity in critically ill obese patients.
AB  - Almost one-third of intensive care unit (ICU) patients are obese. Obese patients
      pose a unique challenge for preventing skin breakdown, healing wounds, and
      preventing complications of surgery and prolonged immobility. Yet little research
      to date has been done to study the effects of obesity on skin integrity and wound
      healing in this patient population. This article discusses common skin conditions
      and wound complications associated with obese patients and general treatment
      guidelines as they pertain to the critically ill patient.

PMID- 19840713
TI  - Sedation considerations for the nonintubated obese patient in critical care.
AB  - Sedation of the obese critical care patient presents unique challenges that
      include altered respiratory function and a predisposition to respiratory
      suppression and airway obstruction. Sedative drugs have pronounced effects on
      obese patients. Knowledge of the anatomic and physiologic changes associated with
      obesity, airway management, and sedation agents better prepares one to care for
      these patients safely and effectively.

PMID- 19840714
TI  - Providing nutrition to critically ill obese adults: use of the nursing process.
AB  - Caring for obese critically ill patients is not always the same as caring for
      critically ill patients who are not obese. Fortunately, nurses have many
      resources available to them to guide them in this process. However, research that
      specifically addresses the needs of obese critically ill patients is still
      lacking in many areas and should be considered as potential areas to develop
      evidence-based practices.

PMID- 19840715
TI  - Impact of obesity on care of postoperative coronary bypass patients.
AB  - Obesity has become a major health problem in the United States and is well known
      to be a risk factor for the development of cardiovascular disease. Many
      clinicians perceive obesity, particularly severe or morbid obesity, to be
      associated with increased risk for mortality and morbidity following coronary
      artery bypass graft (CABG) surgery. This article provides a review of the
      literature related to mortality and morbidity, including the impact of diabetes,
      risk for acute respiratory failure, and sternal wound infection associated with
      obese patients undergoing CABG surgery. Implications for nursing practice are
      addressed with recommendations for practice in this patient population.

PMID- 19840716
TI  - Trauma in obese patients: implications for nursing practice.
AB  - Recently, the impact of obesity on the outcomes of trauma patients has been the
      focus of several investigations. There have been several studies addressing the
      impact of obesity on trauma patients. These studies have explicated the impact of
      obesity on negative outcomes of trauma patients. Several studies have identified
      a relationship between obesity and injury pattern, increased complications in
      outcomes related to surgical procedures, and increase mortality and morbidity
      rates in obese trauma patients. However, the literature in nursing management in
      this patient population is virtually nonexistent and vague. The purpose of this
      article is to delineate the nursing implications of obesity in trauma patients
      and to provide guidelines for care of obese trauma patients.

PMID- 19840717
TI  - Obesity-related risks and prevention strategies for critically ill adults.
AB  - In America today, more than one third of adults are obese. Increasingly, obese
      patients are admitted to critical care units. Critical care nurses must have
      additional knowledge and skills to identify health risks to obese patients and
      implement interventions to prevent untoward problems. Critical care nurses are
      also at risk when taking care of obese patients. The purpose of this article is
      to identify risks to both patients and nurses and to provide recommendations to
      address those risks.

PMID- 19840718
TI  - The impact of obesity on critical care resource use and outcomes.
AB  - Obese patients in the ICU present unique challenges to the health care team and
      specific challenges to nurses. This article reviews the science and art of
      resource use for obese patients in the ICU. Staff nurses and advanced practice
      nurses can make important contributions in evaluating optimal resource use and
      improving outcomes in this population of vulnerable patients.

PMID- 19840719
TI  - When and how to strengthen the superior oblique muscle.
AB  - PURPOSE: To review the history of procedures used to strengthen the action of the
      superior oblique (SO) muscle and methods of quantifying surgical dosage and to
      determine the relationship between congenital onset and tendon laxity measured at
      the time of surgery. METHODS: We reviewed medical records over a 10-year period
      of 30 patients who had undergone SO tendon tuck for SO muscle palsy using
      intraoperative assessment of forced ductions to determine surgical dosage. We
      also designed and tested a modified Bishop tucker, which can simultaneously
      measure tendon shortening and the force required. This allowed development of
      length tension curves between 0 and 200 g for individual SO tendons in patients
      with and without evidence of muscle palsy. RESULTS: In distinction to most other
      procedures on the extraocular muscles, intraoperative forced ductions are used to
      determine appropriate surgical dosage. Patients undergoing SO tendon tuck using a
      uniform and repeatable forced duction method receive a greater amount of tuck
      (mean, 3 mm) when there is known congenital onset. Patients with congenital SO
      muscle palsy received a mean tuck of 10.8 mm (range, 8-16 mm), whereas patients
      with equivocal or known adult-onset SO palsy received a mean of 7.8 mm (range, 4
      12 mm; p = 0.002). CONCLUSIONS: Patients with congenital SO muscle palsy have
      increased tendon laxity when measured directly during SO tendon tuck. The
      excursion of presumed normal SO tendons through the trochlea is variable and may
      be less than previously thought. Modifying the Bishop tucker to provide length
      and tension data provides information that may be useful in determining surgical
      dosage.

PMID- 19840720
TI  - Image analysis for retinopathy of prematurity diagnosis.
AB  - PURPOSE: To review findings from the authors' published studies involving
      telemedicine and image analysis for retinopathy of prematurity (ROP) diagnosis.
      METHODS: Twenty-two ROP experts interpreted a set of 34 wide-angle retinal images
      for presence of plus disease. For each image, a reference standard diagnosis was
      defined from expert consensus. A computer-based system was used to measure
      individual and linear combinations of image parameters for arteries and veins:
      integrated curvature (IC), diameter, and tortuosity index (TI). Sensitivity,
      specificity, and receiver operating characteristic areas under the curve (AUC)
      for plus disease diagnosis were determined for each expert. Sensitivity and
      specificity curves were calculated for the computer-based system by varying the
      diagnostic cutoffs for arterial IC and venous diameter. Individual vessels from
      the original 34 images were identified with particular diagnostic cutoffs, and
      combined into composite wide-angle images using graphics editing software.
      RESULTS: For plus disease diagnosis, expert sensitivity ranged from 0.308-1.000,
      specificity from 0.571-1.000, and AUC from 0.784 to 1.000. Among computer system
      parameters, one linear combination had AUC 0.967, which was greater than that of
      18 of 22 (81.8%) experts. Composite computer-generated images were produced using
      the arterial IC and venous diameter values associated with 75% under-diagnosis of
      plus disease (ie, 25% sensitivity cutoff), 50% under-diagnosis of plus disease
      (ie, 50% sensitivity cutoff), and 25% under-diagnosis of plus disease (ie, 75%
      sensitivity cutoff). CONCLUSIONS: Computer-based image analysis has the potential
      to diagnose severe ROP with comparable or better accuracy than experts, and could
      provide added value to telemedicine systems. Future quantitative definitions of
      plus disease might improve diagnostic objectivity.

PMID- 19840721
TI  - Retinopathy of prematurity in extremely low birth weight infants in Malaysia.
AB  - PURPOSE: To identify differences in incidence, risk factors, and outcomes of
      retinopathy of prematurity (ROP) between 2 birth weight categories within a
      cohort of extremely low birth weight (ELBW) infants in Malaysia. METHODS: This
      was a prospective study of infants in the Special Care Nursery at the University
      of Malaya Medical Centre between 2003 and 2005. Outcome measures were presence or
      absence of ROP, most severe stage of ROP observed, and whether laser treatment
      was performed. Risk factors for treatment were analyzed in this cohort of treated
      patients, who were further divided into groups of birth weight <751 g and birth
      weight 751-1,000 g. RESULTS: The study protocol identified 70 qualifying ELBW
      infants. Of these, 41 (58.6%) developed ROP and 23 (32.9%) required laser
      treatment. Mean birth weight was 806.8 g (SD +/- 142.5); mean gestation was 27.4
      weeks (SD +/- 2.2). Infants with birth weight <750 g were twice as likely to
      require treatment (OR = 2, p = 0.038). The risk factors for laser treatment by
      bivariate analysis were gestation <28 weeks (OR = 1.8, p = 0.001), duration of
      ventilation >1 week (OR = 1.5, p = 0.012), and intraventricular hemorrhage (OR =
      2.5, p = 0.010). Zone 1 ROP was observed only in infants <751 g. CONCLUSIONS: The
      incidence of ROP in ELBW infants in Malaysia is comparable to that seen in the
      ETROP and CRYO-ROP studies. Within this group, birth weight <750 g doubled the
      likelihood that treatment would be required.

PMID- 19840722
TI  - Effect of granulocyte colony-stimulating factor on the incidence of threshold
      retinopathy of prematurity.
AB  - PURPOSE: To study the effect of granulocyte colony-stimulating factor (GCSF) on
      the incidence of threshold retinopathy of prematurity (ROP). METHODS: A
      retrospective chart review of all neonates who received GCSF at our neonatal
      intensive care unit over a period ranging from January 2003 to September 2007 was
      performed. Of the 213 patients identified, 50 patients with birth weight <1,500 g
      and gestational age <32 weeks were included in this study. The incidence of
      threshold ROP in this subset was compared to a control group (n = 161) obtained
      from Vermont Oxford Network ROP database over the same time period. The two data
      sets were cross-referenced to exclude any patient receiving GCSF from the control
      data. RESULTS: The average birth weight was 913 g in GCSF patients and 847 g in
      controls. The average dose of GCSF was 10.4 microg (range, 1.2-21.6 microg). The
      average age at administration of GCSF was 12 days after birth (range, 0-34 days).
      Out of 50 patients in the GCSF group, 5 (10%) required laser treatment, whereas
      in the contol group, 30 (18.6 %) required laser treatment; this difference was
      not statistically significant. CONCLUSIONS: There was a suggestion of a decreased
      incidence of threshold ROP, leading to reduced need for laser treatment, in
      patients who received GCSF, but the observed differences were not statistically
      significant. The authors anticipate that these findings will lead to further
      study of the upstream regulators of neovascularization.

PMID- 19840723
TI  - Outcomes of cataract surgery following radiation treatment for retinoblastoma.
AB  - PURPOSE: To report the outcomes after cataract extraction in eyes previously
      treated for retinoblastoma. METHODS: We reviewed the medical records of
      consecutive patients treated with cataract extraction at our institution for
      radiation-induced cataract following retinoblastoma treatment between 1992 and
      2007. RESULTS: Twelve eyes of 11 patients were included. The median age at
      diagnosis of retinoblastoma was 7.4 months. The median quiescent interval before
      cataract surgery was 34.6 months (range, 17-240 months). All patients underwent
      limbal-based extracapsular cataract extraction with scleral-tunnel wound
      construction. Anterior vitrectomy and posterior capsulotomy were performed in 7
      eyes; an intraocular lens was placed in 10 eyes. A laser capsulotomy was
      subsequently performed in 5 eyes. No postoperative complications occurred. One
      patient underwent a pars plana vitrectomy for vitreous hemorrhage and
      proliferative retinopathy 5 years after cataract extraction. The median follow-up
      after surgery was 6.0 years (range, 1.1-12.3 years). Final visual acuity was
      between 20/20 and 20/60 in 6 eyes, between 20/70 and 20/200 in 2 eyes, and worse
      than 20/200 in 4 eyes. No intraocular tumor recurrences or metastases occurred.
      Two patients developed secondary rhabdomyosarcomas; 1 patient succumbed to the
      disease. CONCLUSIONS: Limbal-based cataract extraction in our series was not
      associated with tumor recurrence or metastasis. The optimal quiescent interval is
      not known; however, no tumor recurrences occurred in our series when a minimum 17
      month quiescent period was achieved. Visual improvement was noted in every
      patient, although several patients only experienced modest gains.

PMID- 19840724
TI  - The value of serial personal photographs in timing the onset of unilateral
      cataracts in children.
AB  - PURPOSE: To determine the value of serial personal photographs in timing the
      onset of unilateral cataracts in children over 6 months of age. METHODS: Personal
      photographs from children with unilateral cataracts who underwent cataract
      extraction and intraocular lens implantation when > or =6 months of age were
      reviewed. Photographs were evaluated for changes in the red reflex, which might
      indicate the presence of a cataract. RESULTS: Twelve children underwent cataract
      surgery at a mean age of 37 months. They were followed for a mean of 32 months.
      Ten children were diagnosed as having an acquired cataract by photographic review
      documenting a previously normal red reflex. The visual acuity in the affected eye
      of 4 of these children improved to > or =20/60. Cataracts were visible on
      photographs prior to clinical diagnosis in 6 patients, from 0.5 to 22 months
      prior to clinical diagnosis. Visual outcomes did not relate closely to the
      photographically documented duration of the cataract prior to treatment.
      Photographs were not helpful in timing the onset of cataract in 2 children due to
      the poor quality of the images. CONCLUSIONS: Serial personal photographs are
      sometimes helpful in determining whether cataracts are acquired. However, the
      usefulness of personal photographs alone in predicting the visual outcome after
      cataract surgery was limited in this small, retrospective study.

PMID- 19840725
TI  - Which Leber congenital amaurosis patients are eligible for gene therapy trials?
AB  - BACKGROUND: In 2007, clinical trials began for gene-replacement therapy for RPE65
      associated Leber congenital amaurosis. To enroll, subjects must have both disease
      causing RPE65 alleles identified. Determining which patients have true disease
      causing mutations requires a multistep approach. METHODS: This study is a
      retrospective case series using the estimate of pathogenic probability (EPP)
      algorithm and genotyping of family members to establish phase. RESULTS: Five
      probands and their families were studied. Patient 1 had genetic testing elsewhere
      and was reported to have 2 disease-causing AIPL1 mutations. The family received
      incorrect prenatal counseling based on this result. We found both variations to
      be benign ethnic polymorphisms (EPP = 0). Case 2 had possible disease-causing
      mutations in RPE65, RPGRIP1, and CRB1; however, screening of family members
      revealed that only CRB1 variations were disease causing and the RPE65 change was
      a polymorphism found in 11% of African Americans. Case 3 had a diagnosis of CRB1
      associated Leber congenital amaurosis, but this mutation had an EPP = 0; a true
      homozygous disease-causing mutation was later found in RDH12. Patient 4 had 3
      mutations found in RPE65, but only 2 were disease causing. Patient 5 had a
      homozygous mutation in RPE65. Only Patients 4 and 5 would be eligible for
      clinical trials of RPE65 gene replacement. CONCLUSIONS: To be eligible for
      participation in current RPE65 gene therapy trials, patients' DNA must contain 2
      correctly segregating alleles with an EPP = 2 or 3. Interpretation of DNA
      variants is complex; genetic misdiagnosis may lead to ineffective treatment in
      some patients and lack of treatment in others.

PMID- 19840726
TI  - Accuracy of the Welch Allyn SureSight for measurement of magnitude of astigmatism
      in 3- to 7-year-old children.
AB  - PURPOSE: To evaluate the accuracy of the Welch Allyn SureSight in noncycloplegic
      measurements of astigmatism as compared to cycloplegic Retinomax K+ autorefractor
      measurements of astigmatism in children from a Native American population with a
      high prevalence of high astigmatism. METHODS: Data are reported for 825 3- to 7
      year-old children with no ocular abnormalities. Each child had a Retinomax K+
      cycloplegic measurement of right eye astigmatism with a confidence rating > or =8
      and 3 attempts to obtain a SureSight measurement on the right eye. RESULTS:
      SureSight measurement success rates did not differ significantly across age or
      measurement confidence rating (<6 vs > or =6). Ninety-six percent of children had
      at least 1 measurement (any confidence), and 89% had at least 1 measurement with
      confidence at the manufacturer's recommended value (> or =6). Overall, the
      SureSight tended to overestimate astigmatism. If the SureSight measurement had
      any dioptric value (0.00 D to 3.00 D), astigmatism of 2.00 D or less was likely
      to be present. If the SureSight showed astigmatism beyond the instrument's
      dioptric range (>3.00 D), Retinomax K+ measurements indicated that >2.00 D of
      astigmatism was present in 136 of 157 (86.6%). In cooperative children for whom
      the SureSight would not give a reading, 32 of 34 (94%) had >3.00 D of
      astigmatism. CONCLUSIONS: The SureSight does not provide an accurate,
      quantitative measure of amount of astigmatism. However, it does allow accurate
      categorization of amount of astigmatism as < or =2.00 D, >2.00 D, or >3.00 D, and
      it has high measurement success rate in young children.

PMID- 19840727
TI  - The psychosocial aspects of strabismus: correlation between the AS-20 and DAS59
      quality-of-life questionnaires.
AB  - PURPOSE: To compare two quality-of-life (QoL) scales and subscales: the Derriford
      Appearance Scale 59 (DAS59) and the Adult Strabismus-20 (AS-20) scale in a series
      of strabismic and nonstrabismic patients and to illustrate the differences in
      results between strabismic and nonstrabismic patients. METHODS: The DAS59 is a
      self-report QoL questionnaire generating an assessment of distress caused by
      problems of appearance. The AS-20 is a newly developed strabismus specific QoL
      scale. A prospective, noninterventional study of a series of consecutive adult
      patients undergoing strabismus surgery and a control group was performed.
      Patients were given both questionnaires to complete before surgery. The
      underlying condition, previous number of surgeries, and deviation measurements
      were recorded. RESULTS: Thirty-four patients and 30 controls correctly completed
      both questionnaires. In the strabismus group, the mean AS-20 score was 50.5. The
      mean DAS59 score was 122.5 (out of 269). There is strong correlation between the
      scales (r = -0.813; 95% CI, -0.90 to -0.66; p < 0.0001). In the control group,
      the AS-20 score was 98.8 and the DAS59, 84.4, with both showing significant
      differences to the strabismic group (t = 12.9 [p < 0.0001] and t = -4.642 [p <
      0.0001], respectively). CONCLUSIONS: The AS-20 shows strong correlation to the
      widely used DAS59. Strabismus patients show significantly more psychosocial
      distress than controls. The AS-20 is specific to strabismus patients and the
      result is not influenced by any other systemic factors that can impinge on the
      more general DAS59 scale.

PMID- 19840728
TI  - Predictive factors of surgical outcome in oculomotor nerve palsy.
AB  - PURPOSE: To investigate the outcomes and predictive factors of surgical treatment
      of oculomotor nerve palsy. METHODS: Records of patients requiring eye muscle
      surgery for oculomotor nerve palsy in our institution were retrospectively
      reviewed. Age, sex, etiology, deviation, completeness of involvement, time
      between onset and surgery, botulinum toxin treatment, and number of surgical
      procedures were recorded as potential predictive factors. Muscle function,
      presence of diplopia, and torticollis were also recorded. The main outcome
      measure was motor function. Secondary outcome measures were presence of diplopia,
      torticollis, and limitation of muscle function. RESULTS: Surgery was required in
      22 patients, of whom motor success was obtained in 14 (63.6%). Frequency of
      diplopia and torticollis were significantly reduced by surgery. After
      multivariate regression analysis, longer time between onset and surgery (p =
      0.03) and larger initial deviation (p = 0.05) were significantly associated with
      poorer postsurgical results in terms of motor function. CONCLUSIONS: Longer time
      from onset to surgery and larger eye deviation are negative prognostic factors of
      postsurgical motor success for oculomotor nerve palsy.

PMID- 19840729
TI  - Traumatic superior oblique tendon rupture.
AB  - Traumatic rupture of an extraocular muscle is rare, and most commonly affects the
      horizontal and vertical rectus muscles. We report a case of a 45-year-old man
      injured by a metal hook, with rupture of the superior oblique tendon. The
      resulting deficit was less severe than expected, raising the question of whether
      a few superior oblique fibers remained intact.

PMID- 19840731
TI  - Septo-optic dysplasia with bilateral congenital corneal anesthesia.
AB  - Septo-optic dysplasia, or de Morsier syndrome, is characterized by optic nerve
      hypoplasia with an absent septum pellucidum and/or pituitary abnormalities.
      Congenital corneal anesthesia is a rare disorder that has been associated with
      many neurological disorders. Here we present a patient with both conditions who
      was successfully treated with permanent lateral tarsorrhaphy and aggressive
      lubrication. To our knowledge, congenital corneal anesthesia has not been
      reported in association with septo-optic dysplasia. The purpose of this report is
      to make pediatric ophthalmologists aware of a potential association since the
      diagnosis of congenital corneal anesthesia is often difficult and delayed.

PMID- 19840730
TI  - A child with bilateral orbital cellulitis one day after strabismus surgery.
AB  - Orbital cellulitis is a rare complication of strabismus surgery. We report a case
      of a 4-year-old boy with bilateral orbital cellulitis after uneventful surgery to
      correct esotropia. Concomitant sinusitis was the likely source of infection. To
      our knowledge, this is the first case of bilateral orbital cellulitis following
      strabismus surgery.

PMID- 19840732
TI  - Semiautomated digital image analysis of posterior pole vessels in retinopathy of
      prematurity.
AB  - Plus disease is a major indicator for treatment in retinopathy of prematurity
      (ROP), and computer-assisted image analysis of vessel caliber and tortuosity in
      the posterior pole may indicate disease progression and severity. We sought to
      determine whether semiautomated digital analysis of posterior pole vessels using
      narrow field images with varying severity of ROP correlated with vessel width and
      tortuosity.

PMID- 19840733
TI  - Image analysis of posterior pole vessels identifies type 1 retinopathy of
      prematurity.
AB  - Identification of type 1 retinopathy of prematurity (ROP) relies heavily on the
      presence of characteristics of plus disease, especially tortuosity. However, a
      relatively infrequent subset of eyes with type 1 ROP, eyes with zone 1, stage 3
      ROP without plus disease, is included in treatment indications. We examined if
      posterior pole vessel width is associated with type 1 ROP in a subset of eyes
      with zone 1, stage 3 ROP without plus disease and whether vessel width
      differentiates type 1 from non-type 1 ROP.

PMID- 19840734
TI  - Longitudinal assessment of plus disease in retinopathy of prematurity using color
      Doppler imaging.
AB  - Retinal vascular changes and the development of plus disease are the hallmarks of
      retinopathy of prematurity (ROP). The purpose of this study was to evaluate
      whether or not serial examinations of retrobulbar blood flow characteristics, as
      measured by color Doppler imaging (CDI) performed repeatedly over a period of
      several weeks, would be useful for predicting those infants at risk for
      developing plus disease and to determine whether this technique may be used as an
      objective tool for confirming the presence of plus disease. Of the 73 infants
      followed in this study, 14 (19%) developed plus disease confirmed by a panel of
      experts. When comparing the group of infants developing plus disease with those
      infants who did not develop plus disease, we did not find any significant
      differences in the retrobulbar blood flow characteristics of either the central
      retinal or ophthalmic arteries. Color Doppler imaging did not appear to be a
      clinically useful tool in the longitudinal management of ROP, nor did it appear
      to be useful as an objective determinant of plus disease in these premature
      infants.

PMID- 19840735
TI  - Juvenile xanthogranuloma masquerading as melanoma.
AB  - Juvenile xanthogranuloma (JXG) of the uvea is a rare disease that usually
      responds to systemic steroids or low-dose radiotherapy. We present an atypical
      case of bilateral JXG involving the entire uveal tract that presented with an
      aggressive phenotype. The patient was unresponsive to topical and systemic
      corticosteroids, cyclosporine, and maximal doses of radiation therapy. The
      disease was ultimately controlled with the alkylating agent chlorambucil.

PMID- 19840736
TI  - Successful treatment of ligneous conjunctivitis with topical cyclosporine and
      heparin.
AB  - Ligneous conjunctivitis is a rare disease characterized by wood-like
      pseudomembranes developing on the ocular and extraocular mucosae. We present a
      case of ligneous conjunctivitis and cataracts in a 10-year-old boy with a
      positive family history of the disease and consanguinity. His condition was
      managed with topical cyclosporine, heparin, and steroids.

PMID- 19840737
TI  - A novel method for management of conjunctival inclusion cysts following
      strabismus surgery using isopropyl alcohol with paired injection technique.
AB  - Conjunctival inclusion cysts following strabismus surgery are typically treated
      by surgical excision in a hospital setting. Cysts may be aspirated in the office
      setting with the aid of a slit lamp, but this approach is associated with
      recurrence. Thermal cautery and intracyst injection of doxycycline may also be
      performed in the office. We present 2 cases of conjunctival inclusion cysts
      treated with isopropyl alcohol injection in an office setting. There was no
      recurrence at 9 months follow-up.

PMID- 19840738
TI  - Resolution of recurrent conjunctival papilloma after topical and intralesional
      interferon alpha2b with partial excision in a child.
AB  - The human papilloma virus (HPV) is a double-stranded DNA virus that infects the
      epithelium of skin and mucosa. Simple treatment of conjunctival papilloma is
      associated with recurrences, and while most medical therapy has met with limited
      success, interferon alpha 2b (IFN alpha2b) may be effective. In this report, we
      describe a 7-year-old child with severe, recurrent conjunctival papilloma who had
      complete regression of the papilloma after topical and intralesional IFN alpha2b
      with partial excision of the lesion.

PMID- 19840739
TI  - Extraocular muscle hypertrophy in myotonia congenita: Mutation identified in the
      SCN4A gene (V445M).

PMID- 19840740
TI  - The critical period for surgical treatment of dense congenital bilateral
      cataracts.

PMID- 19840741
TI  - Congenital osteoma cutis of the lateral canthus.

PMID- 19840744
TI  - Treatment of severe amblyopia with weekend atropine: Results from 2 randomized
      clinical trials.

PMID- 19840746
TI  - Neglected rupture of the Achilles tendon treated with a percutaneous technique.
AB  - INTRODUCTION: Neglected rupture of Achilles tendon is an infrequent but
      debilitating injury. Several surgical methods of treatment have been described to
      repair neglected Achilles tendon rupture. MATERIAL AND METHODS: In our study we
      reviewed 20 patients (18 male and 2 female). We describe a new surgical technique
      using percutaneous repair of the neglected Achilles tendon ruptures. It consists
      of 10 micro-incisions, five lateral and five medial to the posterior aspect of
      the Achilles tendon, the suture is performed using an absorbable number 1 Vicryl
      (Ethicon, Edinburgh UK) inserted percutaneously in a figure of eight fashion.
      RESULTS: The advantages of this procedure are a short time immobilization, an
      early weight bearing and a return to complete ankle range of motion. The mean
      AOFAS score was 99.0, no re-ruptures or sural nerve damage were observed. In all
      the treated patients the results obtained were rated from good to excellent.
      CONCLUSION: We would like to encourage this technique as being fast, inexpensive
      and very satisfactory both to the patient and to the surgeon.

PMID- 19840747
TI  - The stop screw technique--a simple and reliable method in treating flexible
      flatfoot in children.
AB  - PURPOSE: The purpose of this study was to evaluate the stop screw method inserted
      with a minimal invasive technique in the treatment of flexible flatfoot in
      children. MATERIALS AND METHODS: We evaluated the results in a series of 21 flat
      feet in the age group ranging from 8 to 14 years between 1999 and 2007. The
      correction was evaluated clinically by assessment of heel valgus angle, range of
      motion of the ankle joint, and the photopodographic grading. The radiological
      assessment was performed by measuring the talonavicular angulation (Meary's
      line). RESULTS: At time of follow-up there was significant improvement in the
      heel valgus angle during rest and during tiptoe standing, significant improvement
      in the dorsiflexion from neutral position, and in podographic grading.
      Radiologically talonavicular angulation improved significantly from 162+/-8.9
      degrees preoperatively to 174+/-5.8 degrees postoperatively. CONCLUSION: We can
      conclude that subtalar arthroereisis is relatively simple, effective, and
      minimally invasive procedure in treating flexible flatfoot in pediatric age.

PMID- 19840749
TI  - Endoscopic-assisted repair of acute Achilles tendon rupture with Krackow suture:
      an anatomic study.
AB  - PURPOSE: To study the feasibility of applying Krackow locking stitches in the
      endoscopic-assisted repair of acute Achilles tendon rupture and the possible
      complications encountered. TYPE OF STUDY: Anatomic study. METHODS: Twelve
      Achilles tendons in six cadavers were cut at 6cm from its insertion and
      endoscopic-assisted repair of Achilles tendon was performed. These legs were then
      cut open in midline to study (i) the locking stitches formed and (ii) the
      relation of the sural nerve to the locking stitches. RESULT: With endoscopic
      assisted technique, Krackow-type locking stitches can be formed in eight legs. In
      four legs, the stitches fell into the ruptured gap and lie deep to the tendon.
      The tendon rupture end was grasped by the suture rather than forming a Krackow
      type locking stitch when the suture was tightened. There was no sural nerve
      laceration noted. However, in two legs, the sural nerves were found trapped in
      the sutures at around the proximal portal. CONCLUSIONS: Krackow locking stitches
      can be formed by the minimally invasive technique. However, there are risks of
      stitches falling into the ruptured gap and lie deep to the tendon and risk of
      sural nerve entrapment at the proximal medial portal. The original technique is
      not suitable for clinical application. Modification of the technique by grasping
      the tendon end with Allis tissue forceps before passing the suture may prevent
      the suture from falling into the ruptured tendon gap.

PMID- 19840748
TI  - Effect of vitamin C on prevention of complex regional pain syndrome type I in
      foot and ankle surgery.
AB  - BACKGROUND: The public health cost impact of complex regional pain syndrome type
      I (CRPS I) is considerable in both emergency and scheduled orthopaedic surgery.
      We proposed to assess the effectiveness of vitamin C in prevention of CRPS I in
      foot and ankle surgery. METHODS: We carried out a "before-after" quasi
      experimental study comparing two chronologically successive groups without (Group
      I: July 2002-June 2003) and with (Group II: July 2003-June 2004) preventive 1g
      daily vitamin C treatment. All patients having surgery on the foot or ankle were
      enrolled, with the exception of diabetic foot cases. Several factors were
      analysed: sex, age, type of pathology, history of CRPS I, psychological context,
      tourniquet time, and cast immobilisation time. RESULTS: 420 feet (392 patients)
      were included in the study: 185 in Group I, 235 in Group II. CRPS I occurred in
      18 cases in Group I (9.6%) and 4 cases in Group II (1.7%) (p<10(-4)), with
      history of CRPS I as a significantly correlated factor (relative risk=10.4). The
      psychological context (anxio-depressive state) showed a (sub-significant)
      tendency to increase the risk of CRPS I (relative risk=2.6). CONCLUSION: Vitamin
      C has been shown to be effective in preventing CRPS I secondary to wrist
      fracture, but few data are available with respect to foot and ankle cases. The
      present study demonstrates the effectiveness of vitamin C in preventing CRPS I of
      the foot and ankle-a frequent complication in our control group (9.6%). The
      authors recommend preventive management by vitamin C.

PMID- 19840750
TI  - Long-term outcome and quality of life in patients with Charcot foot.
AB  - BACKGROUND: There is only sparse scientific data about the long-term effects of
      the Charcot foot on patients' lives and the clinical outcome. This study
      evaluates the long-term effects of diabetic Charcot foot. METHODS: A cross
      sectional follow-up study of consecutive series of patients with Charcot foot
      referred to the University Hospital Diabetic Foot and Ankle Clinic between 1991
      and 2002. RESULTS: Forty-one patients were referred with Charcot foot between
      1991 and 2002. After an average follow-up of 8 years their overall mortality rate
      was 29% (12/41) and 29 patients (30 Charcot feet) have been followed more than 5
      years. Sixty-seven percent of Charcot feet suffered at least one episode of
      ulceration and 50% (15/30) of affected feet had surgical treatment resulting in
      29 operations. Simple exostectomy was successful in 62% of cases. The need for
      surgical management increased markedly 4 years after the diagnosis. Correct
      diagnosis within 3 months resulted in better functional outcome (AOFAS) and
      walking distance (p=0.006 and p=0.008, respectively). Lower SF-36 component
      scores in physical functioning, social functioning and general health perceptions
      were found when the study population was compared to the general population and
      chronically ill control subjects. CONCLUSIONS: Diabetic Charcot foot decreases
      patient's physical functioning and general health but does not usually affect
      mental health. Surgical management is often required with an increase 4 years
      post-diagnosis. A delay of diagnosis of more than 3 months was found to adversely
      affect the quality of life and functional outcome.

PMID- 19840751
TI  - A retrospective follow-up of ankle fracture patients treated with a biodegradable
      plate and screws.
AB  - BACKGROUND: Biodegradable fixation implants have been developed to avoid
      secondary hardware removal. The aim of this study was to retrospectively follow
      up ankle fracture patients treated with a biodegradable plate and screws, and to
      evaluate the clinical outcome and occurrence of complications. METHODS: Fifty
      seven ankle fracture patients treated with biodegradable implants were invited,
      and a total of 50 were available to participate in this study. The follow-up
      included a review of each patient's medical records, evaluation of radiographs,
      fracture reduction classification, and functional scoring. RESULTS: There were 36
      lateral malleolar and 14 bimalleolar fractures. No perioperative complications
      occurred. Average follow-up time was 17 months. All fractures healed. Fracture
      alignment was classified as anatomical in 49 patients and good in 1 case. The
      mean Olerud and Molander functional ankle score at final follow-up was 86. Eight
      patients had postoperative complications. These included delayed wound healing in
      1 case, 3 cases of deep-vein thrombosis, and 4 soft tissue reactions.
      CONCLUSIONS: According to the results of this retrospective study, the
      biodegradable implants used yielded fracture healing and functional results
      comparable to those previously reported after conventional metal fixation.

PMID- 19840752
TI  - Is intraoperative pedography helpful in clinical use--preliminary results of 100
      cases from a consecutive, prospective, randomized, controlled clinical study.
AB  - BACKGROUND: The purpose of this study was to assess the clinical use, and to
      analyze the potential clinical benefit of intraoperative pedography (IP) in a
      sufficient number of cases in comparison with cases treated without IP. METHODS:
      Patients (age 18 years and older) which sustained an arthrodesis and/or
      correction of the foot and ankle were included. RESULTS: One hundred cases were
      included (ankle correction arthrodesis, n=12; subtalar joint correction
      arthrodesis, n=14; arthrodesis without correction midfoot, n=15; correction
      arthrodesis midfoot, n=26; correction forefoot, n=33). Fifty-two patients were
      randomized for the use of IP. In 24 of the 52 patients (46%), the correction was
      modified after IP during the same operation. CONCLUSIONS: In 46% of the cases a
      modification of the surgical correction was made after IP in the same surgical
      procedure. Whether IP improve the plantar force distribution of the foot and the
      mid- or long-term clinical outcome has to be critically analyzed when longer
      follow-up is completed.

PMID- 19840753
TI  - Retained blackthorn causing peroneal tendonitis: a case report.
AB  - We present the first reported case of peroneal tenosynovitis secondary to a
      retained blackthorn in a patient with a 4 months history of persistent pain and
      swelling around her lateral malleolus following a penetrating injury.
      Ultrasonography reported considerable subcutaneous fluid but no identifiable
      foreign body. Magnetic resonance imaging confirmed peroneal sheath synovitis with
      a possible retained foreign body posteriorly. Surgical exploration revealed
      marked synovitis and chronic inflammation of the peroneal sheath with the tip of
      a blackthorn deep to peroneus longus. This case illustrates the many ways in
      which penetrating blackthorn injuries may present. In particular it highlights
      the need for a high index of suspicion for retained foreign material and the need
      for further imaging and surgical exploration when symptoms do not resolve.

PMID- 19840754
TI  - Malunited calcaneal fracture fragments causing tarsal tunnel syndrome: a rare
      cause.
AB  - This is a report of tarsal tunnel syndrome (TTS) due to a specific malunited
      calcaneal fracture fragment in a 46-year-old man. He was treated non-operatively
      for extra-articular calcaneal fracture. Four months later he presented with pain,
      tingling and hypoaesthesia over the medial aspect of the heel. He had a positive
      Tinel's sign and a positive dorsiflexion-eversion test. Radiography revealed
      malunited calcaneal fracture along medial wall producing bony prominence. The
      tarsal tunnel was surgically decompressed by excising the malunited fragments.
      The branches of the posterior tibial nerve were stretched over these fragments
      intra-operatively. There was symptomatic improvement with surgical excision of
      the fragment, however, the hypoesthesia did not resolve completely. Appropriate
      initial treatment will help to prevent this complication.

PMID- 19840755
TI  - Re: the use of post-operative reverse camber shoes following scarf osteotomy,
      Foot Ankle Surg 14 (2008) 190-193.

PMID- 19840756
TI  - A zebrafish gene trap line expresses GFP recapturing expression pattern of
      foxj1b.
AB  - Foxj1 has been found to play an important role in cilia formation and function in
      vertebrates. The zebrafish or Xenopus genome expresses two Foxj1 genes,
      foxj1a/FoxJ1 and foxj1b/FoxJ1.2. In this study, we have generated a zebrafish
      transgenic line T2BGSZ10 by To l 2 transposon-based gene trapping approach.
      T2BGSZ10 transgenic fish carry an insertion of the transposon genome into the
      first intron of the foxj1b locus. This insertion results in GFP expression in the
      forebrain, otic vesicles, floorplate, pronephric ducts and other domains during
      embryogenesis, which recaptures the expression pattern of foxj1b. Although normal
      expression of foxj1b is dramatically reduced, T2BGSZ10 homozygous embryos develop
      normally and grow to adulthood without detectable defects, which may be due to
      the incomplete interruption of foxj1b expression. Nevertheless, this transgenic
      line may serve as a useful model for dynamic observation of GFP-labeled tissues
      and organs and for isolation of GFP-labeled cells.

PMID- 19840757
TI  - Bioinformatic analysis of microRNA biogenesis and function related proteins in
      eleven animal genomes.
AB  - MicroRNAs are approximately 22 nt long small non-coding RNAs that play important
      regulatory roles in eukaryotes. The biogenesis and functional processes of
      microRNAs require the participation of many proteins, of which, the well studied
      ones are Dicer, Drosha, Argonaute and Exportin 5. To systematically study these
      four protein families, we screened 11 animal genomes to search for genes encoding
      above mentioned proteins, and identified some new members for each family. Domain
      analysis results revealed that most proteins within the same family share
      identical or similar domains. Alternative spliced transcript variants were found
      for some proteins. We also examined the expression patterns of these proteins in
      different human tissues and identified other proteins that could potentially
      interact with these proteins. These findings provided systematic information on
      the four key proteins involved in microRNA biogenesis and functional pathways in
      animals, and will shed light on further functional studies of these proteins.

PMID- 19840758
TI  - Evolution of double MutT/Nudix domain-containing proteins: similar domain
      architectures from independent gene duplication-fusion events.
AB  - The MutT/Nudix superfamily proteins repair DNA damage and play a role in human
      health and disease. In this study, we examined two different cases of double
      MutT/Nudix domain-containing proteins from eukaryotes and prokaryotes. Firstly,
      these double domain proteins were discovered in Drosophila, but only single Nudix
      domain proteins were found in other animals. The phylogenetic tree was
      constructed based on the protein sequence of Nudix_N and Nudix_C from Drosophila,
      and Nudix from other animals. The phylogenetic analysis suggested that the double
      Nudix domain proteins might have undergone a gene duplication-speciation-fusion
      process. Secondly, two genes of the MutT family, DR0004 and DR0329, were fused by
      two mutT gene segments and formed double MutT domain protein genes in Deinococcus
      radiodurans. The evolutionary tree of bacterial MutT proteins suggested that the
      double MutT domain proteins in D. radiodurans probably resulted from a gene
      duplication-fusion event after speciation. Gene duplication-fusion is a basic and
      important gene innovation mechanism for the evolution of double MutT/Nudix domain
      proteins. Independent gene duplication-fusion events resulted in similar domain
      architectures of different double MutT/Nudix domain proteins.

PMID- 19840759
TI  - Analysis of expressed receptor-like kinases (RLKs) in soybean.
AB  - Receptor-like kinases (RLKs) play crucial roles in cellular signal perception and
      propagation. To study the evolutionary relationships among RLKs in soybean, a
      large-scale expressed sequence tags (ESTs) survey for RLKs-related sequences was
      conducted. By doing BLAST analysis using our database and The Gene Index
      Database, 605 putative RLK genes were identified. Based on the phylogeny of the
      kinase domain, these soybean RLKs were classified into 58 different small
      subfamilies. The phylogenetic analysis of RLKs in soybean, rice and Arabidopsis
      showed that different subfamilies of RLKs had different functions and could have
      experienced different selective pressures.

PMID- 19840760
TI  - Distinguishing transgenic from non-transgenic Arabidopsis plants by (1)H NMR
      based metabolic fingerprinting.
AB  - We have recently reported the construction of an nuclear magnetic resonance (NMR)
      based metabonomics study platform, Automics. To examine the application of
      Automics in transgenic plants, we performed metabolic fingerprinting analysis,
      i.e., (1)H NMR spectroscopy and multivariate analysis, on wild-type and
      transgenic Arabidopsis. We found that it was possible to distinguish wild-type
      from four transgenic plants by PLS-DA following application of orthogonal signal
      correction (OSC). Scores plot following OSC clearly demonstrates significant
      variation between the transgenic and non-transgenic groups, suggesting that the
      metabolic changes among wild-type and transgenic lines are possibly associated
      with transgenic event. We also found that the major contributing metabolites were
      some specific amino acids (i.e., threonine and alanine), which could correspond
      to the insertion of the selective marker BAR gene in the transgenic plants. Our
      data suggests that NMR-based metabonomics is an efficient method to distinguish
      fingerprinting difference between wild-type and transgenic plants, and can
      potentially be applied in the bio-safety assessment of transgenic plants.

PMID- 19840761
TI  - A comparative proteomics approach to detect unintended effects in transgenic
      Arabidopsis.
AB  - Recently, as part of biosafety assessments, unintended effects have been given
      much attention. In this study, we applied a proteomics approach to elucidate the
      unintended effects of random T-DNA insertion in transgenic plants. Separated
      proteins extracted from 12 trans-genic Arabidopsis thaliana with different T-DNA
      insertion sites and from wild-type (ecotype Col-o) were analyzed. In the
      transgenic plants, 102 significantly altered protein spots were detected, in
      which 59 were up-regulated and 43 down-regulated. MALDI-TOF MS analysis showed
      that most of these expression level-altered proteins were involved in energy
      transfer, oxidative respiration and photosynthesis. However, none of these
      proteins was a toxic protein or allergen. Using plants with or without cold
      treatment, a natural environmental stress, as controls, we found that the number
      of the altered proteins was even less in those transgenic plants than those
      triggered by the cold treatment, suggesting that the transgenic events had a
      weaker impact on the plants than the environmental stresses. Interestingly, the
      phosphinothricin acetyl transferase (PAT), the BAR-encoded protein, was detected
      in nine out of twelve different T-DNA insertion lines at five different insertion
      sites. These data suggest that the most significant impact of transgenic events
      on the host plants is from the transgene itself, i.e., from the predictable
      intended effects, rather than unintended effects. This study also suggests that
      the proteomics approach has the potential to detect the unintended effects in
      transgenic plants.

PMID- 19840762
TI  - Activation of NFkB and coagulation in lung injury by hyperoxia and excessive
      mechanical ventilation: one more reason "low and slow" is the way to go?

PMID- 19840763
TI  - Gammadelta T cells and Th17 cytokines in hypersensitivity pneumonitis and lung
      fibrosis.
AB  - Hypersensitivity pneumonitis (HP) is an inflammatory lung disease caused by the
      repeated inhalation of aerosolized antigens. With chronic exposure to an inhaled
      antigen, patients are at risk of developing irreversible pulmonary fibrosis as
      well as an increased morbidity and mortality. Although alphabeta T cells have
      been shown to be important in the pathogenesis of HP, gammadelta T cells also
      accumulate in the bronchoalveolar lavage of patients with HP. gammadelta T cells
      represent a distinct lymphocyte subset, whose primary function is not well
      understood. In contrast to alphabeta T cells, gammadelta T cells recognize
      unprocessed antigens, such as those upregulated on injured or stressed epithelial
      cells. In a murine model of HP induced by exposure to the ubiquitous
      microorganism Bacillus subtilis, gammadelta T cells expressing the canonical
      Vgamma6/Vdelta1 T cell receptor were dramatically expanded in the lung. The
      predominant cytokines expressed by this gammadelta T-cell subset were T-helper 17
      (Th17) cytokines that were critical for bacterial clearance and the resolution of
      lung inflammation. Th17-expressing gammadelta T cells are also expanded in other
      murine models of lung infection and inflammation, which suggests that these cells
      play a sentinel role in mucosal immunity. Thus, an increased understanding of
      gammadelta T cells that express Th17 cytokines in HP and other inflammatory lung
      diseases may lead to the development of novel therapeutic and clinical strategies
      that prevent the development of fibrotic lung disease.

PMID- 19840764
TI  - Role for nuclear factor-kappaB in augmented lung injury because of interaction
      between hyperoxia and high stretch ventilation.
AB  - High-tidal-volume mechanical ventilation and hyperoxia used in patients with
      acute lung injury (ALI) can induce alveolar coagulopathy and fibrin depositions
      within the airways. Hyperoxia has been shown to increase ventilator-induced lung
      injury (VILI), but the mechanisms that regulate interaction between high-tidal
      volume mechanical ventilation and hyperoxia are unclear. We hypothesized that
      mechanical stretch with hyperoxia synergistically augmented neutrophil
      infiltration and production of plasminogen activator inhibitor-1 (PAI-1) via the
      nuclear factor-kappaB (NF-kappaB) pathway. C57BL/6 mice (n=5 per group) were
      exposed to high-tidal-volume (30 mL/kg) or low-tidal-volume (6 mL/kg) mechanical
      ventilation with room air or hyperoxia for 1 to 5h after 2-microg/g NF-kappaB
      inhibitor (SN-50) administration. Nonventilated mice with room air or hyperoxia
      served as control groups. Evans blue dye, myeloperoxidase, electrophoretic
      mobility shifting of nuclear protein, and inflammatory cytokine were measured.
      The expression of tumor necrosis factor-alpha (TNF-alpha) and PAI-1 were studied
      by immunohistochemistry. The addition of hyperoxia to high-tidal-volume
      ventilation-augmented lung injury, as demonstrated by increased microvascular
      leak, neutrophil migration into the lung, TNF-alpha and active PAI-1 production,
      DNA binding activity of NF-kappaB, and NF-kappaB activation. No statistically
      significant increase of neutrophil infiltration and inflammatory cytokine
      production was found in the mice ventilated at 6 mL/kg using hyperoxia. Hyperoxia
      induced augmentation of VILI was attenuated in mice with pharmacologic inhibition
      of NF-kappaB activity by SN-50. We conclude that hyperoxia increased high-tidal
      volume-induced cytokine production and neutrophil influx through activation of
      the NF-kappaB pathway.

PMID- 19840765
TI  - Effects of etanercept on sodium taurocholate-induced acute pancreatitis in rats.
AB  - In this study, we examined the effects of etanercept (ETA) on experimentally
      induced pancreatitis. Acute pancreatitis was induced with Na taurocholate. ETA
      was simultaneously administered to treatment groups. Serum amylase and lipase
      activity, pancreatic histopathology, apoptosis, malondialdehyde (MDA), and
      myeloperoxidase enzyme activity (MPO) were assessed. Although rats in the groups
      1, 2, and 3 were sacrificed 24h later, groups 4, 5, and 6 were sacrificed 5 days
      later. ETA treatment significantly decreased serum amylase activity (nontreated,
      2636.16+/-191.94; treated, 1898.71+/-262.53; control, 506.28+/-17.31 U/L,
      P<0.001), lipase activity (nontreated, 3049.67+/-972.65; treated, 2538.85+/
      660.45; control, 88.57+/-7.54 U/L, P<0.001), histopathologic score (nontreated,
      5.43+/-0.43; treated, 2.57+/-0.20; control, 0.71+/-0.18, P<0.001), MDA
      (nontreated, 105.77+/-13.29; treated, 92.89+/-10.39; control, 41.26+/-2.54
      nmol/g, P<0.001), and MPO (nontreated, 0.64+/-1.15; treated, 0.59+/-0.13;
      control, 0.17+/-0.02 units/g/wet weight, P<0.001) activity in 24-h groups. In 5
      day groups, ETA treatment decreased amylase activity (nontreated, 738.67+/-48.60;
      treated, 497.14+/-47.25; control, 389.00+/-9.17 U/L, P<0.001), lipase activity
      (nontreated, 101.33+/-39.32; treated, 34.57+/-7.29; control, 23.42+/-2.12 U/L,
      P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 3.71+/-0.68;
      control, 0.00+/-0.00, P<0.001), MDA (nontreated, 67.91+/-4.28; treated, 60.91+/
      3.57; control, 14.85+/-1.16 nmol/g, P<0.001), and MPO (nontreated, 0.36+/-0.04;
      treated, 0.27+/-0.02; control, 0.14+/-0.02 units/g/wet weight, P<0.001) activity.
      Caspase-positive cells numbers around the necrosis significantly decreased by ETA
      treatment in both 24-h groups (nontreated, 74.28+/-3.26; treated, 67.00+/-1.15;
      control, 3.85+/-0.63, P<0.001) and 5-day groups (nontreated, 79.85+/-3.01;
      treated, 47.85+/-5.76; control, 2.22+/-0.63, P<0.001). These results showed that
      ETA has an ameliorating effect on sodium taurocholate-induced acute necrotic
      pancreatitis.

PMID- 19840766
TI  - Gender differences in correlates of troponin assay in diagnosis of myocardial
      infarction.
AB  - Cardiac troponins are the most sensitive and specific biomarker for myocardial
      infarction (MI) diagnosis. If there is a gender bias in MI diagnosis, it could be
      reduced by more consistently applying objective diagnostic criteria to improve
      women's outcomes. This study set out to assess the accuracy and correlates of the
      cardiac troponin I (cTnI) assay in the diagnosis of non-ST-segment elevation MI,
      to determine how the assay accuracy and correlates vary by gender, and to explore
      the interaction between factors that may influence cTnI accuracy and affect
      gender differences in diagnosis. The data were obtained from the CHECKMATE study.
      It included 924 patients with possible myocardial ischemia excluding subjects
      with ST-segment elevation. The Dade-Behring Stratus CS STAT near-patient
      instrument (Dade Behring, Inc, Newark, Del) was used to measure cTnI. We assessed
      baseline troponin accuracy using a standard MI definition. There were 125
      subjects with a definite MI diagnosis. Baseline troponin was 44% sensitive and
      97% specific in predicting MI, with no significant gender differences. In
      contrast, other positive cardiac markers, namely rising or falling creatine
      kinase MB fraction and positive electrocardiogram, occurred more frequently in
      men. Sensitivity (SE) of baseline troponin was higher in subjects where baseline
      troponin was obtained longer than 2 hours after the chest pain onset. The study
      did not observe a significant difference in the assay SE or specificity by
      gender. This observation, plus the fact that other positive cardiac markers
      occurred more frequently in men, suggest the troponin test may help to improve
      the diagnosis of MI in women.

PMID- 19840767
TI  - Interactive association of heat shock protein 70 genes variants with natural
      longevity in Xinjiang Hetian Uygur ethnicity.
AB  - Mounting evidence suggests that all organisms at the cellular level respond to
      stress by synthesizing heat shock proteins at the expense of other proteins, and
      the ability of human cells to respond to heat stress decreases with aging. We
      thus investigate the association of 3 variants (A1267G in HSPA1B, G190C in
      HSPA1A, and T2437C in HSPA1L) in the heat shock protein 70 (Hsp70) family with
      natural longevity in a Xinjiang Hetian Uygur population. A case-control study was
      conducted in 191 healthy individuals greater than 90 years of age, and 53
      naturally died persons 65-70 years of age. Promoter activity was evaluated by
      luciferase reporter assays. The data were analyzed using an EH/EH+ program for
      haplotype prediction and MDR software for gene-gene interaction. All studied
      variants satisfied the Hardy-Weinberg equilibrium in each group. In single-locus
      analysis, no significant differences were found between long-lived people and
      short-lived people in the genotype/allele distributions of all variants. In
      contrast, haplotype analysis indicated that haplotypes A-G-C and A-C-T were more
      prevalent in long-lived people than short-lived people (P=0.026 and 0.017), and
      the analysis conferred a 3.46- and 4.51-fold increased tendency for longevity,
      respectively (P=0.025 and 0.016). The haplotype results were strengthened by
      interaction analysis, which suggests an optimal model in which G190C and T2437C
      exert an interacting effect on longevity. No functional significance was observed
      between 190G and 190C alleles in both control and heat-inducible A549 cells
      (P>0.05). Taken together, our findings suggested that common genetic variants in
      Hsp70 family might contribute interactively to longevity the Xinjiang Hetian
      Uygur population.

PMID- 19840768
TI  - Relationship between sex hormones and idiopathic outflow tract ventricular
      arrhythmias in adult male patients.
AB  - Sex hormones and gender differences have been reported to be associated with the
      occurrences of ventricular arrhythmias. This study investigated the relationship
      between sex hormones and idiopathic outflow tract ventricular arrhythmias (IOTVA)
      in adult male patients. Serum sex hormonal levels, which include testosterone,
      estradiol, and progestogen, were measured by using commercially prepared
      immunoassay kits. The average count of premature ventricular contractions (PVCs)
      (number/24h) was assessed by 72h electrocardiographic monitoring. No differences
      were found in the levels of testosterone and progestogen between the IOTVA male
      patients and the control males (both P>0.05). However, the level of estradiol in
      the IOTVA male patients was significantly lower than that in the control males
      (P<0.05). A significant negative correlation was observed between the number of
      PVCs and the level of estradiol in the IOTVA male patients (r=0.702, P<0.05). The
      current study suggested that IOTVA might be associated with the reduction of
      estradiol level in adult male patients.

PMID- 19840769
TI  - Respiratory syncytial virus infection of camels (Camelus dromedaries).
AB  - This study aimed to investigate the occurrence of respiratory syncytial virus
      (RSV) infections in camels in Sudan. A total of 272 camel lung specimens showing
      pneumonia were collected from slaughter houses at four different areas in Sudan,
      additionally 8 specimens were collected from outbreaks of respiratory infection
      in camels. Using sandwich ELISA kits for RSV antigen detection 4 out of 280
      tested lungs (1.4%) were positive, all were from Central Sudan (Tambool slaughter
      house). FAT was used to confirm the ELISA positives. Polymerase chain reaction
      RT/PCR was applied for the detection of RSV genome in camel lungs; 1 out of 4
      ELISA positives was positive by RT/PCR. Using indirect ELISA kits 135 out of 495
      (27.3%) camel sera showed antibodies to RSV, highest prevalence was observed in
      Western (33.5%) then Central (31.6%) and Eastern Sudan (23.5%). Based on the
      manufacturer specified calculations for OD readings, most of positive sera
      (90/135) were low reactive (1+). This is the first report for the detection of
      RSV antigen, genome and antibody in camels in Sudan.

PMID- 19840770
TI  - Solid-state (2)H and (15)N NMR studies of side-chain and backbone dynamics of
      phospholamban in lipid bilayers: investigation of the N27A mutation.
AB  - Phospholamban (PLB) is an integral membrane protein regulating Ca(2+) transport
      through inhibitory interaction with sarco(endo)plasmic reticulum calcium ATPase
      (SERCA). The Asn27 to Ala (N27A) mutation of PLB has been shown to function as a
      superinhibitor of the affinity of SERCA for Ca(2+) and of cardiac contractility
      in vivo. The effects of this N27A mutation on the side-chain and backbone
      dynamics of PLB were investigated with (2)H and (15)N solid-state NMR
      spectroscopy in phospholipid multilamellar vesicles (MLVs). (2)H and (15)N NMR
      spectra indicate that the N27A mutation does not significantly change the side
      chain or backbone dynamics of the transmembrane and cytoplasmic domains when
      compared to wild-type PLB. However, dynamic changes are observed for the hinge
      region, in which greater mobility is observed for the CD(3)-labeled Ala24 N27A
      PLB. The increased dynamics in the hinge region of PLB upon N27A mutation may
      allow the cytoplasmic helix to more easily interact with the Ca(2+)-ATPase; thus,
      showing increased inhibition of Ca(2+)-ATPase.

PMID- 19840771
TI  - Functional characterization of a Na(+)-coupled dicarboxylate transporter from
      Bacillus licheniformis.
AB  - The Na(+)-coupled dicarboxylate transporter, SdcL, from Bacillus licheniformis is
      a member of the divalent anion/Na(+) symporter (DASS) family that includes the
      bacterial Na(+)/dicarboxylate cotransporter SdcS (from Staphyloccocus aureus) and
      the mammalian Na(+)/dicarboxylate cotransporters, NaDC1 and NaDC3. The transport
      properties of SdcL produced in Escherichia coli are similar to those of its
      prokaryotic and eukaryotic counterparts, involving the Na(+)-dependent transport
      of dicarboxylates such as succinate or malate across the cytoplasmic membrane
      with a K(m) of approximately 6 microM. SdcL may also transport aspartate, alpha
      ketoglutarate and oxaloacetate with low affinity. The cotransport of Na(+) and
      dicarboxylate by SdcL has an apparent stoichiometry of 2:1, and a K(0.5) for
      Na(+) of 0.9 mM. Our findings represent the characterization of another
      prokaryotic protein of the DASS family with transport properties similar to its
      eukaryotic counterparts, but with a broader substrate specificity than other
      prokaryotic DASS family members. The broader range of substrates carried by SdcL
      may provide insight into domains of the protein that allow a more flexible or
      larger substrate binding pocket.

PMID- 19840772
TI  - Interaction of nicotinamide and picolinamide with phosphatidylcholine and
      phosphatidylethanolamine membranes: a combined approach using dipole potential
      measurements and quantum chemical calculations.
AB  - Interaction between the bioactive compounds nicotinamide and picolinamide and
      phospholipids (phosphatidylcholines and phosphatidylethanolamines) was
      investigated by a combined approach using dipole potential measurements and
      quantum chemical calculations. It is shown that nicotinamide and picolinamide
      interactions with phosphatidylcholines are of two main types: (i) specific
      interactions with the phosphate group of the lipid, for which H-bonding between
      NH(2) group of the substrate and the phosphate plays a dominant role, (ii)
      conjugated less specific weaker interactions involving both the phosphate and
      carbonyl groups of the head group, which propagate to the lipid alkyl chains and
      increase their conformational disorder. For phosphatidylethanolamines,
      picolinamide was found to decrease the dipole potential of the membrane in a
      similar way as for phosphatidylcholines, while nicotinamide is ineffective. These
      findings are correlated with the specific properties of phosphatidylethanolamines
      (reduced exposure of phosphate groups) and structural differences in the two
      substrates, in particular: different separation of the nitrogen atoms in the
      molecules, existence of a strong intramolecular hydrogen bond in picolinamide
      (NH...N ((ring))), which is absent in nicotinamide, and non-planarity of
      nicotinamide molecules, in contrast to picolinamide ones. Additional information
      on the lipid/substrate interactions was extracted from the analysis of the
      changes produced in the relevant vibrational frequencies of the lipid and
      substrate upon binding. The present study gives molecular support to the argument
      that changes of dipole potentials are due to effects on the constitutive dipolar
      PO and CO groups. In addition, it is also shown that according to the specific
      binding of the substrate to one or both of those, the conformational state of the
      acyl chains may be affected. These entropy effects may be in the origin of the
      well-known interdependence of the properties of one monolayer with respect to the
      other in bilayer membranes.

PMID- 19840773
TI  - Galanin is highly expressed in bone marrow mesenchymal stem cells and facilitates
      migration of cells both in vitro and in vivo.
AB  - Galanin peptide has recently been found to be highly abundant in early embryonic
      mouse mesenchyme, while galanin and its receptors are expressed in embryonic
      mouse stem cells. Bone marrow mesenchymal stem cells (BMMSCs) represent the
      primary source for adult stem cell therapy. In this study we examined the
      abundance of galanin and its receptors in BMMSCs and evaluated its possible
      function. Galanin mRNA and protein were highly expressed in BMMSCs cultures up to
      four passages, while among the three galanin receptor subtypes (GalR1, GalR2, and
      GalR3) only GalR2 and to a lesser extent GalR3 were expressed. Using chemotaxis
      and wound assays we found that galanin protein increased the migration of BMMSCs.
      Furthermore, increased serum galanin levels in a galanin transgenic model
      enhanced the mobilization (homing) of injected BMMSCs in vivo. These data suggest
      a role for galanin in BMMSC migration, probably through activation of the GalR2
      receptor.

PMID- 19840774
TI  - The activity-dependent stimuli increase SUMO modification in SHSY5Y cells.
AB  - Post-translational modification of proteins by the small ubiquitin-like modifiers
      (SUMOs) has emerged as an important regulatory mechanism for alteration of
      protein activity, stability, and cellular localization. It has been reported that
      SUMOylation plays an important role in some activities of neuronal cells.
      However, the link between SUMOylation and activity-dependent stimuli of neurons
      remains to be elucidated. Here we showed that KCl-induced depolarization
      increased SUMO conjugation in SHSY5Y cell line in a time-dependent manner. The
      increase of SUMOylation was largely dependent on calcium influx and intracellular
      calcium signals. Our study demonstrates the link between the activity-dependent
      stimuli and global SUMOs conjugation, which may play an important role in
      activity-dependent signals of neurons.

PMID- 19840775
TI  - Foxo1 is essential for in vitro vascular formation from embryonic stem cells.
AB  - The forkhead transcription factors regulate the correct organization of vascular
      system. One of them, Foxo1 is an important physiological regulator of endothelial
      cell morphology in response to VEGF, while underlying mechanisms are largely
      unknown. In order to elucidate the cellular function of Foxo1, we used a three
      dimensional culture system for the differentiation of Flk1-expressing mesodermal
      precursor cells derived from ES cells to cord forming endothelial cells and
      associating vascular smooth muscle cells. While Foxo1(+/+) endothelial cells
      organized into long vessel-like structures associated with smooth muscle cells,
      Foxo1(-/-) endothelial cells could form only short sprouts. Foxo1(-/-)
      endothelial cells have punctate accumulation of filamentous actin, thick
      circumferential bundles of microtubules with small spikes at the tip of cells,
      and no interaction with smooth muscle cells. Our results suggest the involvement
      of Foxo1 in cytoskeletal remodeling of endothelial cells and recruitment of
      smooth muscle cells during vascular development.

PMID- 19840776
TI  - Lithium modulates tryptophan hydroxylase 2 gene expression and serotonin release
      in primary cultures of serotonergic raphe neurons.
AB  - Lithium salts are mood-stabilizing agents with acute antimanic properties and
      proven efficacy in the long-term prevention of manic and depressive episodes.
      Furthermore, lithium augmentation is a well-established strategy to treat
      depressed patients, which do not respond to antidepressants alone. There is
      evidence to suggest that these effects of lithium are due to a synergism with
      central serotonin (5-HT) neurotransmission. In this study, we investigated the
      effects of lithium chloride (LiCl, 1 mM) on 5-HT uptake and release in primary
      serotonergic neurons from rat raphe nuclei. Short-term (8 h) and long-term (14
      days) treatment with LiCl resulted in a 20% and 23% increase in 5-HT release, but
      neither influenced 5-HT uptake across the plasma membrane nor vesicular 5-HT
      uptake. In lithium-treated raphe neurons, the inhibition of 5-HT uptake by
      fluoxetine was unchanged. Using real-time reverse transcriptase polymerase chain
      reaction and Western blotting, we examined the effect of lithium on tryptophan
      hydroxylase 2 (TPH2) expression, the rate-limiting enzyme in brain 5-HT
      biosynthesis. Short-term lithium treatment resulted in a 45% decrease in tph2
      mRNA expression and a 31% reduction of TPH2 protein levels, which was completely
      compensated after long-term treatment. Our results suggest that lithium can
      modify tph2 gene expression and 5-HT release in raphe neurons, providing new
      insight into the serotonergic mechanisms of action of lithium.

PMID- 19840777
TI  - Bio-released gold ions modulate expression of neuroprotective and hematopoietic
      factors after brain injury.
AB  - The discovery of neural stem cells (NSCs) provides new therapeutic strategies for
      brain injury by means of endogenous cell renewal. In the injured mouse brain, bio
      liberated gold ions from gold implants mediate anti-inflammatory and
      antiapoptotic effects and activation of NSCs. This paper investigates the
      neuroprotective effects of gold following brain injury in mice. We show for the
      first time that endogenous NSCs express macrophage colony-stimulating factor (M
      CSF) as part of their post-injury activation and that gold implants increase this
      response. Also, gold increases expression of neurotrophin (NT)-4, transforming
      growth factor-beta 3 (TGF-beta 3), leukemia inhibitory factor (LIF) and
      metallothionein I+II (MT-I+II) post-injury. This paper shows that gold ions
      modulate neurotrophic factors after injury and that hematopoietic factor M-CSF is
      expressed in activated NSCs.

PMID- 19840778
TI  - Increased sensitivity to kainic acid in a genetic model of reduced NMDA receptor
      function.
AB  - The pathophysiology of schizophrenia may involve reduced NMDA receptor function
      and experimental models of NMDA receptor hypofunction have proven useful for
      characterizing neurobiological abnormalities potentially relevant to
      schizophrenia. The present study assessed behavioral responses and induction of
      Fos after administration of kainic acid to wild type mice (NR1(+/+)) and mice
      with genetically reduced NMDA receptor expression (NR1(neo/neo)). At a dose of 20
      mg/kg, kainic acid induced lethal seizures in 100% of the NR1(neo/neo) mice
      tested but produced no lethal seizures in the wild type mice. The NR1(neo/neo)
      mice also exhibited enhanced behavioral responses to kainic acid at a dose of 15
      mg/kg but no lethal seizures were produced by this dose. A greater induction of
      Fos was observed in neocortical and limbic cortical regions of the NR1(neo/neo)
      compared to NR1(+/+) mice after administration of 15 mg/kg kainic acid. In
      contrast, there were no differences between the genotypes in kainic acid induced
      Fos in the amygdala, hippocampus, lateral septum, and nucleus accumbens. In order
      to determine if altered behavioral phenotypes of the NR1(neo/neo) mice could be
      related to increased sensitivity of kainate receptors to endogenous glutamate,
      effects of the highly selective kainate antagonist LY382884 were examined. The
      kainate antagonist reduced the exaggerated acoustic startle responses, deficits
      in prepulse inhibition of acoustic startle, and motor hyperactivity in the
      NR1(neo/neo) mice. These findings suggest that selective kainate receptor
      antagonists could be novel therapeutic candidates for schizophrenia.

PMID- 19840779
TI  - Edaravone, a free radical scavenger, protects components of the neurovascular
      unit against oxidative stress in vitro.
AB  - The concept of the neurovascular unit suggests that to be successful, stroke
      therapies must protect all neuronal, glial and endothelial components in brain.
      In this study, we tested the efficacy of the free radical scavenger edaravone in
      three cellular models of oxidative stress. HT22 neuronal cells were subjected to
      oxidative stress using the standard glutamate-induced glutathione depletion
      model. Primary rat astrocytes were exposed to H(2)O(2). Oxidative stress was
      induced in human brain endothelial cells with sodium nitroprusside (SNP).
      Edaravone significantly reduced oxidative cell death in both HT22 neuronal cells
      and primary rat astrocytes in a dose-dependent manner. SNP did not kill brain
      endothelial cells but instead reduced their production of brain-derived
      neurotrophic factor (BDNF). Edaravone significantly ameliorated this response.
      These data suggest that free radical scavengers are effective in all cell types
      of the neurovascular unit, and should still be considered as a potential
      therapeutic approach for stroke.

PMID- 19840780
TI  - A microinjection technique for targeting regions of embryonic and neonatal mouse
      brain in vivo.
AB  - A simple pressure injection technique was developed to deliver substances into
      specific regions of the embryonic and neonatal mouse brain in vivo. The
      retrograde tracers Fluorogold and cholera toxin B subunit were used to test the
      validity of the technique. Injected animals survived the duration of transport
      (24-48 h) and then were sacrificed and perfused with fixative. Small injections
      (<or=50 nL) were contained within targeted structures of the perinatal brain and
      labeled distant cells of origin in several model neural pathways. Traced neural
      pathways in the perinatal mouse were further examined with immunohistochemical
      methods to test the feasibility of double labeling experiments during
      development. Several experimental situations in which this technique would be
      useful are discussed, for example, to label projection neurons in slice or
      culture preparations of mouse embryos and neonates. The administration of
      pharmacological or genetic vectors directly into specific neural targets during
      development should also be feasible. An examination of the form of neural
      pathways during early stages of life may lead to insights regarding the
      functional changes that occur during critical periods of development and provide
      an anatomic basis for some neurodevelopmental disorders.

PMID- 19840782
TI  - A new capillary zone electrophoresis method for the screening of congenital
      disorders of glycosylation (CDG).
AB  - BACKGROUND: The Congenital Disorders of Glycosylation (CDG) are an expanding
      group of metabolic diseases with a broad clinical presentation. We sought to
      validate a new Capillary Zone Electrophoresis (CZE) method (Sebia Capillarys CDT)
      to screen for CDG. METHODS: We analyzed 119 serum samples from children of
      varying ages and of both sexes to establish a reference range of transferrin
      glycoforms including CDT (Carbohydrate Deficient Transferrin). We then studied
      serums from 8 known CDG patients and compared the CZE results to the Isoelectric
      Focusing (IEF) profiles. We also analyzed serums after extraction from spotted
      Guthrie cards. RESULTS: The mean (SD) percentages of transferrin glycoforms are
      18.5 (4.4), 78.5 (4.2), 2.5 (1.3) and 0.6 (0.3) for penta-, tetra-,
      trisialotransferrin and CDT, respectively. There is no statistically significant
      difference between the different age groups analyzed (0-5, 6-11, 12-15, 16-18,
      and >18 y) or between sexes. We observed a good correlation between the CZE and
      IEF profiles with both fresh serum and serum extracted from Guthrie cards.
      CONCLUSIONS: The Sebia Capillarys CDT system is a simple and reliable method to
      screen for CDG in pediatric and adult patients with an unexplained clinical
      syndrome, particularly when the nervous system is involved.

PMID- 19840781
TI  - Co-treating with arecoline and 4-nitroquinoline 1-oxide to establish a mouse
      model mimicking oral tumorigenesis.
AB  - The aim of this study was to establish an effective mouse model of oral cancer
      and to use this model to identify potential markers of oral tumor progression.
      C57BL/6JNarl mice were treated with arecoline, 4-nitroquinoline 1-oxide (4-NQO),
      or both arecoline and 4-NQO in high and low doses for 8 weeks to induce oral
      tumor. The induced oral lesions were observed for 20 weeks to assess the
      efficiency of cancer induction and survival rate of the mice. In addition, two
      target proteins that are frequently overexpressed during tongue cancer
      tumorigenesis, alphaB-crystallin and Hsp27, were examined by immunohistochemical
      analysis. In mice exposed to 4-NQO (200 microg/mL) and arecoline (500 microg/mL),
      the tongue lesions showed evidence of hyperplasia, papilloma, dysplasia, and
      carcinoma, and the lesions were pathologically similar to those lesions in human
      oral cancer. The tongue tumor incidence rate was 100% in mice exposed to
      concomitant 4-NQO (200 microg/mL) and arecoline (500 microg/mL) treatment, 57% in
      mice exposed to 4-NQO only, and 0% in mice exposed to arecoline only.
      Immunohistochemical analysis demonstrated that, consistent with human studies,
      alphaB-crystallin and Hsp27 were upregulated in murine oral tumors. In
      conclusion, we have established a powerful animal model that enables the study of
      the promoting effects of arecoline on tongue tumorigenesis. Data subsequently
      attained from this mouse model support a role for alphaB-crystallin and Hsp27 as
      clinical markers for tumor progression.

PMID- 19840783
TI  - Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the
      disposition of citalopram.
AB  - We investigate the impact of sex and genotype on citalopram disposition in 35
      healthy volunteers who received an oral dose of 20mg citalopram within a single
      dose bioequivalence study. CYP2C19*2 and *3, and CYP2D6*4 mutations were
      determined by Real-Time PCR. The influence of sex and genotype was analyzed by a
      linear mixed model for repeated measures, including formulation, period,
      sequence, sex, CYP2C19 and CYP2D6 as fixed effects and subject nested
      sequence*sex*CYP2C19*CYP2D6 as the random one. Pharmacokinetic parameters were
      log-transformed and AUC(infinity) and C(max) adjusted to the administered
      dose/weight. The model yields a statistical significance in AUC(infinity) and
      CL/F for CYP2C19 and CYP2D6. Gender, formulation, sequence or period effects were
      not statistically significant. AUC(infinity) of CYP2C19*1/*2 and CYP2C19*2/*2
      carriers is 44% and 118% higher than wild type, respectively; CYP2D6 volunteers
      carrying 1/4 have an AUC 23% higher than wild type. Our data also suggest that
      the influence of CYP2D6 on AUC(infinity) is very low when it is in association
      with CYP2C19*1/*1 while its influence is more apparent in association with
      CYP2C19*1/*2. In conclusion, we demonstrate the influence of CYP2C19 and CYP2D6
      in the disposition of citalopram, and we suggest that the influence of CYP2D6 is
      more probable in volunteers with at least one defective allele of CYP2C19.

PMID- 19840784
TI  - A validation study of a new molecular diagnostic assay: the Dartmouth-Hitchcock
      Medical Center experience with the GeneSearch BLN assay in breast sentinel lymph
      nodes.
AB  - BACKGROUND: Sentinel lymph node (SLN) processing remains variable in terms of
      performing multiple tissue levels and immunohistochemical (IHC) or PCR-based
      assays. A rapid and reliable molecular pathology assay, as an adjunct to routine
      SLN processing, could minimize and standardize the histologic evaluation needed
      for an accurate and clinically significant diagnosis. We compared the recently
      FDA-approved Veridex GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC;
      Warren, NJ), a real time reverse transcriptase-polymerase chain reaction assay
      that is designed to detect metastases >0.2 mm, with our standard lymph node
      processing. MATERIALS AND METHODS: The GeneSearch BLN assay evaluates RNA
      expression data for three target genes (mammaglobin, cytokeratin 19, and internal
      control porphobilinogen deaminase), and provides a qualitative
      (positive/negative) result. In 59 patients, the assay was performed on SLN tissue
      that would normally be deep within the tissue block and not routinely evaluated
      histologically. Two 1 -mm slices from the outer node portions were submitted
      fresh for RNA extraction; the remaining tissue was submitted for routine
      histology. RESULTS: Of the 59 patients, the assay determined 43 as true negative,
      eight as true positive, one as false-negative, three as false-positive, and four
      as invalid. Assay sensitivity was 88.9%, specificity 93.5%. DISCUSSION: The
      sensitivity of the assay sampling from the outer node tissue was high (88.9%) and
      identical to that validated in the large registration study in which half of the
      node was assessed as alternate slices (87.6%). Our protocol uses this assay as an
      adjunct to traditional histologic evaluation, to reduce and standardize the
      number of tissue sections needed for thorough SLN evaluation, and to enhance our
      ability to bank RNA.

PMID- 19840785
TI  - Characteristics of period doubling in the rat cone flicker ERG.
AB  - When the eye is stimulated by a flickering light, the electroretinogram (ERG) and
      other electrophysiological responses in the visual pathway often exhibit period
      doubling. This phenomenon is manifested as an alternation in the shape of the
      response waveform from cycle to cycle, and also as spectral components at the
      half-fundamental frequency (F/2) and its odd multiples. Although period doubling
      has been described in humans as well as in other animals, its features in the
      rodent flicker ERG have not been characterized. We investigated the properties of
      period doubling in the rat cone flicker ERG elicited with full field, sinusoidal
      photic stimuli. Period doubling was observed when the temporal frequency of the
      stimulus was in the range of 20-30 Hz. The F/2 component of the Fourier spectrum
      of the ERG was more pronounced than its odd harmonics. The magnitude of the cycle
      to-cycle variation in amplitude differed depending on whether measurements were
      based on peak-to-trough or trough-to-peak amplitudes, owing to the relative phase
      relationship between F/2 and F as a function of stimulus frequency. The frequency
      response characteristics of period doubling varied with stimulus contrast, such
      that reducing the contrast shifted the peak F/2 amplitude to a lower stimulus
      frequency. Period doubling was evident in rat eyes in which PDA was administered
      intravitreally, indicating that the phenomenon can occur independently of OFF
      pathway activity in the rat retina. The period doubling properties we observed in
      the flicker ERG response of the rat cone system provide constraints on the nature
      of the nonlinear feedback mechanism presumed to underlie the period doubling
      phenomenon.

PMID- 19840786
TI  - In sickness and in health: Corneal epithelial stem cell biology, pathology and
      therapy.
AB  - Our window to the world is provided by the cornea on the front surface of the
      eye. The integrity and functionality of the outermost corneal epithelium is
      essential for vision. A population of limbal epithelial stem cells (LESCs) are
      responsible for maintaining the epithelium throughout life by providing a
      constant supply of daughter cells that replenish those constantly lost from the
      ocular surface during normal wear and tear and following injury. LESC deficiency
      leads to corneal opacification, inflammation, vascularization and discomfort
      (Daniels et al., 2001, 2007). Cultured LESC delivery is one of several examples
      of successful adult stem cell therapy in patients. The clinical precedence for
      use of stem cell therapy and the accessibility of the transparent stem cell niche
      make the cornea a unique model for the study of adult stem cells in physiological
      conditions as well as in disease.

PMID- 19840788
TI  - Axonal and neuronal pathology in multiple sclerosis: what have we learnt from
      animal models.
AB  - Axonal and neuronal injury and loss are of critical importance for permanent
      clinical disability in multiple sclerosis patients. Axonal injury occurs already
      early during the disease and accumulates with disease progression. It is not
      restricted to focal demyelinated lesions in the white matter, but also affects
      the normal appearing white matter and the grey matter. Experimental studies show
      that many different immunological mechanisms may lead to axonal and neuronal
      injury, including antigen-specific destruction by specific T-cells and auto
      antibodies as well as injury induced by products of activated macrophages and
      microglia. They all appear to be relevant for multiple sclerosis pathogensis in
      different patients and at different stages of the disease. However, in MS lesions
      a major mechanism of axonal and neuronal damage appears to be related to the
      action of reactive oxygen and nitrogen species, which may induce neuronal injury
      through impairment of mitochondrial function and subsequent energy failure.

PMID- 19840787
TI  - 5-HT precursor loading, but not 5-HT receptor agonists, increases motor function
      after spinal cord contusion in adult rats.
AB  - Serotonergic (5-HT) receptors are upregulated following spinal cord transection.
      Stimulation by administration of serotonergic receptor agonists has been
      successful in improving hindlimb function. We tested whether this strategy would
      be successful in incomplete injury models (moderate or severe thoracic contusion)
      where descending projections are partially spared which should produce less
      denervation-induced receptor upregulation. Adult rats received midthoracic
      moderate (MOD: 25 mm drop) or severe (SEV: 50 mm drop) contusion injuries.
      Distribution of 5-HT and its transporter and expression of 5-HT(2C) receptors
      were evaluated in lumbar spinal cord and motor response to 5-HT receptor
      activation was assessed using open field locomotion (BBB) score, percent weight
      supported treadmill stepping (%WS) and evaluation of hindlimb muscle activation
      (tremor and serotonin syndrome). 5-HT immunostaining 3 months post-contusion
      revealed few 5-HT fibers caudal to the severe contusion, and more spared caudal
      to the moderate contusion. The distribution of 5-HT transporter paralleled 5-HT
      staining, but was more greatly reduced. Thus serotonin reuptake may be less
      efficient in the injured spinal cord. Immunostaining for the 5-HT(2C) receptor in
      the dorsal and ventral horns at L5 showed significant upregulation in SEV,
      compared to sham or MOD rats. Neither 5-HT(2C) nor 5-HT(1A) receptor agonists,
      alone or in combination, nor the serotonin transporter inhibitor d-fenfluramine
      modified BBB scores or %WS in either group. Despite the increased sensitivity of
      post-synaptic targets, agonist treatment did not improve function in SEV rats. We
      conclude that selective 5-HT(2C) or 5-HT(1A) receptor activation was not
      effective in improving hindlimb function after incomplete lesions. In contrast,
      the 5-HT precursor 5-hydroxytryptophan (L-5-HTP), which leads to activation of
      all classes of 5-HT receptors, increased both %WS and hindlimb activity in the
      MOD group. While no side effects were observed in normal or MOD rats, SEV rats
      displayed hindlimb tremors and 33% mortality, indicating hypersensitivity to the
      precursor.

PMID- 19840789
TI  - Chronic treatment with agonists of beta(2)-adrenergic receptors in neuropathic
      pain.
AB  - Expression of beta(2)-adrenoceptors (beta(2)-ARs) within the nociceptive system
      suggested their potential implication in nociception and pain. Recently, we
      demonstrated that these receptors are essential for neuropathic pain treatment by
      antidepressant drugs. The aim of the present study was to investigate whether the
      stimulation of beta(2)-ARs could in fact be adequate to alleviate neuropathic
      allodynia. Neuropathy was induced in mice by sciatic nerve cuffing. We
      demonstrate that chronic but not acute stimulation of beta(2)-ARs with agonists
      such as clenbuterol, formoterol, metaproterenol and procaterol suppressed
      neuropathic allodynia. By using a pharmacological approach with the beta(2)-AR
      antagonist ICI 118,551 or a transgenic approach with mice deficient for beta(2)
      ARs, we confirmed that the antiallodynic effect of these agonists was
      specifically related to their action on beta(2)-ARs. We also showed that chronic
      treatment with the beta(1)-AR agonist xamoterol or with the beta(3)-AR agonist
      BRL 37344 had no effect on neuropathic allodynia. Chronic stimulation of beta(2)
      ARs, but not beta(1)- or beta(3)-ARs, by specific agonists is thus able to
      alleviate neuropathic allodynia. This action of beta(2)-AR agonists might
      implicate the endogenous opioid system; indeed chronic clenbuterol effect can be
      acutely blocked by the delta-opioid receptor antagonist naltrindole. Present
      results show that beta(2)-ARs are not only essential for the antiallodynic action
      of antidepressant drugs on sustained neuropathic pain, but also that the
      stimulation of these receptors is sufficient to relieve neuropathic allodynia in
      a murine model. Our data suggest that beta(2)-AR agonists may potentially offer
      an alternative therapy to antidepressant drugs for the chronic treatment of
      neuropathic pain.

PMID- 19840790
TI  - A kinome of 2600 in the ciliate Paramecium tetraurelia.
AB  - Protein kinases play a crucial role in the regulation of cellular processes. Most
      eukaryotes reserve about 2.5% of their genes for protein kinases. We analysed the
      genome of the single-celled ciliate Paramecium tetraurelia and identified 2606
      kinases, about 6.6% of its genes, representing the largest kinome to date. A gene
      tree combined with human kinases revealed a massive expansion of the calcium
      calmodulin regulated subfamily, underlining the importance of calcium in the
      physiology of P. tetraurelia. The kinases are embedded in only 40 domain
      architectures, contrasting 134 in human. This might indicate different mechanisms
      to achieve target specificity.

PMID- 19840791
TI  - Differential regulation of p53 function by protein kinase C isoforms revealed by
      a yeast cell system.
AB  - The complexity of the mammalian p53 pathway and protein kinase C (PKC) family has
      hampered the discrimination of the effect of PKC isoforms on p53 activity. Using
      yeasts co-expressing the human wild-type p53 and a mammalian PKC-alpha, -delta, 
      epsilon or -zeta, we showed a differential regulation of p53 activity and
      phosphorylation state by PKC isoforms. Whereas PKC-alpha reduced the p53-induced
      yeast growth inhibition and cell cycle arrest, PKC-delta and -epsilon enhanced
      the p53 activity through p53 phosphorylation, and PKC-zeta had no effect on p53.
      This work identified positive and negative p53 regulators which represent
      promising pharmacological targets in anti-cancer therapy.

PMID- 19840792
TI  - Essential role of TRPV2 ion channel in the sensitivity of dystrophic muscle to
      eccentric contractions.
AB  - Duchenne myopathy is a lethal disease due to the absence of dystrophin, a
      cytoskeletal protein. Muscles from dystrophin-deficient mice (mdx) typically
      present an exaggerated susceptibility to eccentric work characterized by an
      important force drop and an increased membrane permeability consecutive to
      repeated lengthening contractions. The present study shows that mdx muscles are
      largely protected from eccentric work-induced damage by overexpressing a dominant
      negative mutant of TRPV2 ion channel. This observation points out the role of
      TRPV2 channel in the physiopathology of Duchenne muscular dystrophy.

PMID- 19840793
TI  - Differential regulation by ATP versus ADP further links CaMKII aggregation to
      ischemic conditions.
AB  - CaMKII, a major mediator of synaptic plasticity, forms extra-synaptic clusters
      under ischemic conditions. This study further supports self-aggregation of CaMKII
      holoenzymes as the underlying mechanism. Aggregation in vitro was promoted by
      mimicking ischemic conditions: low pH (6.8 or less), Ca(2+) (and calmodulin), and
      low ATP and/or high ADP concentration. Mutational analysis showed that high ATP
      prevented aggregation by a mechanism involving T286 auto-phosphorylation, and
      indicated requirement for nucleotide binding but not auto-phosphorylation also
      for extra-synaptic clustering within neurons. These results clarify a previously
      apparent paradox in the nucleotide and phosphorylation requirement of
      aggregation, and support a mechanism that involves inter-holoenzyme T286-region/T
      site interaction.

PMID- 19840794
TI  - A locally-induced increase in intracellular Ca2+ propagates cell-to-cell in the
      presence of plasma membrane Ca2+ ATPase inhibitors in non-excitable cells.
AB  - Intercellular Ca(2+) waves are commonly observed in many cell types. In non
      excitable cells, intercellular Ca(2+) waves are mediated by gap junctional
      diffusion of a Ca(2+) mobilizing messenger such as IP(3). Since Ca(2+) is heavily
      buffered in the cytosolic environment, it has been hypothesized that the
      contribution of the diffusion of Ca(2+) to intercellular Ca(2+) waves is limited.
      Here, we report that in the presence of plasma membrane Ca(2+) ATPase inhibitors,
      locally-released Ca(2+) from the flash-photolysis of caged-Ca(2+) appeared to
      induce further Ca(2+) release and were propagated from one cell to another,
      indicating that Ca(2+) was self-amplified to mediate intercellular Ca(2+) waves.
      Our findings support the notion that non-excitable cells can establish a highly
      excitable medium to communicate local responses with distant cells.

PMID- 19840795
TI  - Matrilin-3 activates the expression of osteoarthritis-associated genes in primary
      human chondrocytes.
AB  - Here, we tested the matrilin-3-dependent induction of osteoarthritis-associated
      genes in primary human chondrocytes. Matrilin stimulation leads to the induction
      of MMP1, MMP3, MMP13, COX-2, iNOS, IL-1beta, TNFalpha, IL-6 and IL-8.
      Furthermore, we show the participation of ADAMTS4 and ADAMTS5 in the in vitro
      degradation of matrilin-3. We provide evidence for a matrilin-3-dependent feed
      forward mechanism of matrix degradation, whereby proteolytically-released
      matrilin-3 induces pro-inflammatory cytokines as well as ADAMTS4 and -5
      indirectly via IL-1beta. ADAMTS4 and ADAMTS5, in turn, cleave matrilin-3 and may
      release more matrilin-3 from the matrix, which could lead to further release of
      pro-inflammatory cytokines and proteases in cartilage.

PMID- 19840796
TI  - Shaping tubular carriers for intracellular membrane transport.
AB  - The particular compositions of the intracellular membrane organelles rely on the
      proteins and lipids received frequently through membrane trafficking. The
      delivery of these molecules is driven by the membrane-bound organelles known as
      transport carriers (TCs). Advanced microscopy approaches have revealed that TC
      morphology ranges from small vesicles to complex tubular membrane structures.
      These tubular TCs (TTCs) support effectively both sorting and transport events
      within the biosynthetic and endocytic pathways, while a coherent picture of the
      processes that define the formation and further fate of TTCs is still missing.
      Here, we present an overview of the mechanisms operating during the TTC life
      cycle, as well as of the emerging role of tubular carriers in different
      intracellular transport routes.

PMID- 19840797
TI  - Large telomerase RNA, telomere length heterogeneity and escape from senescence in
      Candida glabrata.
AB  - Telomerase, the key enzyme essential for the maintenance of eukaryotic chromosome
      ends, contains a reverse transcriptase and an RNA that provides the template for
      the synthesis of telomeric repeats. Here, we characterize the telomerase subunits
      in the hemiascomycete yeast Candida glabrata. We propose a secondary structure
      model for the telomerase RNA that is the largest described to date. Telomerase
      deletion mutants show a progressive shortening of telomeres and a modest loss of
      viability. Frequent post-senescence survivors emerge that possess long telomeric
      repeat tracts. We suggest that the high telomere length heterogeneity accounts
      for this distinct senescence phenotype.

PMID- 19840798
TI  - Cost-effectiveness of endoscopic screening followed by surveillance for Barrett's
      esophagus: a review.
AB  - Screening interventions for Barrett's esophagus (BE) are appealing, but there is
      little supporting evidence. We reviewed health economics studies about BE
      endoscopic screening followed by, as required, endoscopic surveillance
      ("screening and surveillance" hereafter) to help inform the design and conduct of
      future research. Health economics studies about BE screening and surveillance
      were identified using electronic database searches and personal contact with
      authors of identified studies. No studies examined general population screening.
      Five US studies published between 2003 and 2007 examined the cost effectiveness
      of screening and surveillance (against no intervention) in patients with chronic
      gastroesophageal reflux disease (GERD). There was no randomized trial evidence to
      inform model construction. Assumptions about prevalence and transition
      probabilities between BE histologic subtypes and about surveillance and treatment
      protocols varied substantially between studies. Parameters such as potential BE
      diagnosis-related reduction in quality of life or increase in health care use,
      diagnostic accuracy, and infrastructural costs (for quality assurance) were
      considered either "optimistically" or not at all. Only 2 studies considered
      endoscopic treatments. No study considered the recently introduced radiofrequency
      ablation technique, or the potential for biomarker-based risk stratification of
      surveillance interval or duration. Current health economics evidence is likely to
      have provided optimistic cost-effectiveness estimates and is not sufficient to
      support introduction of endoscopic BE screening programs among GERD patients. The
      evidence does not adequately incorporate novel (endoscopic) treatments and the
      potential for (clinical, endoscopic, or biomarker-based) risk stratification of
      surveillance. Future research should aim to encompass both these factors.

PMID- 19840803
TI  - Annual cycles of urinary reproductive steroid concentrations in wild and captive
      endangered Fijian ground frogs (Platymantis vitiana).
AB  - Annual cycles of reproductive steroid metabolites were measured in urine
      collected from free-living and captive tropical endangered Fijian ground frogs
      (Platymantis vitiana) a terrestrial breeding. Free-living frogs were sampled on
      Viwa Island, Fiji and captive frogs were maintained in an outdoor enclosure in
      Suva, Fiji. Urinary estrone, progesterone and testosterone metabolite
      concentrations increased in male and female frogs after hCG challenges, with
      clear peaks in steroid concentrations 2 or 3 days after the challenges. There
      were annual cycles of testosterone metabolites in wild and captive males, and of
      estrone and progesterone metabolites in wild and captive females. Peaks of
      steroid concentrations in the wet season corresponded with periods of mating and
      egg laying in females in December and January. Steroid concentrations declined in
      January and February when maximum egg sizes in females were also declining. Body
      weights of wild male and vitellogenic female frogs showed annual cycles. Body
      weights of non-vitellogenic female frogs varied significantly between months,
      although there was no clear pattern of annual changes. Body weights of the 3
      captive male frogs and 4 captive female frogs were similar to those of the wild
      frogs. Estrone metabolites were 80% successful in identifying non-vitellogenic
      females from males. The results suggest that the Fijian ground frog is a seasonal
      breeder with an annual gonadal cycle, and this species is likely to be
      photoperiodic. Urinary steroid measurements can provide useful information on
      reproductive cycles in endangered amphibians.

PMID- 19840804
TI  - Brain aromatase mRNA expression in two populations of the peacock blenny Salaria
      pavo with divergent mating systems.
AB  - Aromatase, the key enzyme in the conversion of androgens to estrogens, regulates
      the availability of these hormones in tissues and controls many physiological and
      behavioral processes. In fish and other vertebrates, the regulation of aromatase
      expression in the brain has been implicated in the modulation of male sexual and
      aggressive behaviors. Here, the pattern of mRNA expression of the brain aromatase
      isoform (encoded by the CYP19A2 gene also referred as CYP19b) was quantified at
      the peak of spawning season in brain macroareas from males and females of the
      blenny Salaria pavo originated from two populations displaying male alternative
      reproductive tactics but differing in their mating systems. In Trieste (Adriatic)
      nesting males aggressively defend nests and take the initiative in courtship and
      perform sexual displays more often than females while in Ria Formosa (Southern
      Portugal) the pattern is reversed as a result of shortage of appropriate nesting
      sites. Nesting males from Ria Formosa had overall higher levels of brain
      aromatase mRNA expression than nesting males from Trieste, suggesting a higher
      brain estrogen synthesis in these males. Since in some fish species exogenous
      estradiol administration has been shown to decrease sexual and agonistic
      behaviors, the higher levels of brain aromatase in Ria Formosa nesting males may
      explain their reduced expression of sexual and aggressive displays when compared
      with nesting males from Trieste. Alternatively, the higher brain aromatase levels
      in nesting males from Ria Formosa could be a mechanism to decrease the putative
      androgen-induced activation of aggressive and sexual displays by reducing the
      local availability of androgens through their metabolization into estrogens.
      Although females and parasitic female-like males also differ in their displays
      between populations, the interpopulational pattern of brain aromatase mRNA
      expression was similar, suggesting that other neuroendocrine agents mediate the
      expression of female and female-like behaviors. In conclusion, brain aromatase
      availability seems like a probable mechanism to regulate the effects of steroids
      on the brain circuits underlying the expression of sexual and agonistic displays
      in S. pavo.

PMID- 19840805
TI  - Immune investment impairs growth, female reproduction and survival in the house
      cricket, Acheta domesticus.
AB  - We investigated whether an immune response is associated with growth, female
      reproduction and survival costs in the house cricket. Using different intensities
      of challenge immune (implantation of one piece of nylon (1N) and two nylons (2N),
      with their respective sham-challenge and control groups) with body size and
      exoskeleton thickness as response variables, growth costs were determined for
      both sexes. A similar methodology was followed for reproduction costs, in which
      egg number and size, and female survival were measured as response variables. It
      was also determined whether mated and virgin females showed different immune
      responses. Body size decreased with immune challenge but only in the 2N
      treatment. Exoskeleton thickness increased in both sham-challenge groups and the
      1N group but decreased in the 2N group. Egg number decreased more in the sham
      challenge groups followed by the 1N and 2N groups. The 2N group showed the
      largest egg size at the end of the experiment. In these females, 2N group died
      first followed by the 1N, two nylon sham and one nylon sham groups. Finally,
      mated females showed a lower immune response than virgin females. These results
      are consistent with ecological immunity theory. The discovery of exoskeleton
      related costs of immunity and injury may have important implications for
      experimental design in studies of the cost of immunity.

PMID- 19840806
TI  - Exploring the midgut proteome of partially fed female cattle tick (Rhipicephalus
      (Boophilus) microplus).
AB  - The continued development of effective anti-tick vaccines remains the most
      promising prospect for the control of the cattle tick, Rhipicephalus (Boophilus)
      microplus. A vaccine based on midgut proteins could interfere with successful
      tick feeding and additionally interfere with midgut developmental stages of
      Babesia parasites, providing opportunities for the control of both the tick and
      the pathogens it transmits. Midgut proteins from partially fed adult female
      cattle ticks were analysed using a combination of 2-DE and gel-free LC-MS/MS.
      Analysis of the urea-soluble protein fraction resulted in the confident
      identification of 105 gut proteins, while the PBS-soluble fraction yielded an
      additional 37 R. microplus proteins. The results show an abundance of proteins
      involved in mitochondrial ATP synthesis, electron transport chain, protein
      synthesis, chaperone, antioxidant and protein folding and transport activities in
      midgut tissues of adult female ticks. Among the novel products identified were
      clathrin-adaptor protein, which is involved in the assembly of clathrin-coated
      vesicles, and membrane-associated trafficking proteins such as syntaxin 6 and
      surfeit 4. The observations allow the formulation of hypotheses regarding midgut
      physiology and will serve as a basis for future vaccine development and tick-host
      interaction research.

PMID- 19840807
TI  - A mathematical model of brain tumour response to radiotherapy and chemotherapy
      considering radiobiological aspects.
AB  - Glioblastoma is the most frequent and malignant brain tumour. For many years, the
      conventional treatment has been maximal surgical resection followed by
      radiotherapy (RT), with a median survival time of less than 10 months.
      Previously, the use of adjuvant chemotherapy (given after RT) has failed to
      demonstrate a statistically significant survival advantage. Recently, a
      randomized phase III trial has confirmed the benefit of temozolomide (TMZ) and
      has defined a new standard of care for the treatment of patients with high-grade
      brain tumours. The results showed an increase of 2.5 months in median survival,
      and 16.1% in 2 year survival, for patients receiving RT with TMZ compared with RT
      alone. It is not clear whether the major benefit of TMZ comes from either
      concomitant administration of TMZ with RT, or from six cycles of adjuvant TMZ, or
      both. The objectives were to develop our original model, which addressed survival
      after RT, to construct a new module to assess the potential role of TMZ from
      clinical data, and to explore its synergistic contribution in addition to
      radiation. The model has been extended to include radiobiological parameters. The
      addition of the linear quadratic equation to describe cellular response to
      treatment has enabled us to quantify the effects of radiation and TMZ in
      radiobiological terms. The results indicate that the model achieves an excellent
      fit to the clinical data, with the assumption that TMZ given concomitantly with
      RT synergistically increases radiosensitivity. The alternative, that the effect
      of TMZ is due only to direct cell killing, does not fit the clinical data so
      well. The addition of concomitant TMZ appears to change the radiobiological
      parameters. This aspect of our results suggests possible treatment developments.
      Our observations need further evaluations in real clinical trials, may suggest
      treatment strategies for new trials, and inform their design.

PMID- 19840808
TI  - Identifying translation initiation sites in prokaryotes using support vector
      machine.
AB  - MOTIVATION: Gene identification in genomes has been a fundamental and long
      standing task in bioinformatics and computational biology. Many computational
      methods have been developed to predict genes in prokaryote genomes by identifying
      translation initiation site (TIS) in transcript data. However, the pseudo-TISs at
      the genome level make these methods suffer from a high number of false positive
      predictions. In addition, most of the existing tools use an unsupervised learning
      framework, whose predictive accuracy may depend on the choice of specific
      organism. RESULTS: In this paper, we present a supervised learning method,
      support vector machine (SVM), to identify translation initiation site at the
      genome level. The features are extracted from the sequence data by modeling the
      sequence segment around predicted TISs as a position specific weight matrix
      (PSWM). We train the parameters of our SVM through well constructed positive and
      negative TIS datasets. Then we apply the method to recognize translation
      initiation sites in E. coli, B. subtilis, and validate our method on two GC-rich
      bacteria genomes: Pseudomonas aeruginosa and Burkholderia pseudomallei K96243. We
      show that translation initiation sites can be recognized accurately at the genome
      level by our method, irrespective of their GC content. Furthermore, we compare
      our method with four existing methods and demonstrate that our method outperform
      these methods by obtaining better performance in all the four organisms.

PMID- 19840809
TI  - Diet-induced obesity in the short-day-lean Brandt's vole.
AB  - To test the hypothesis that mammals that show decrease in body mass under short
      day condition should be resistant to high-fat induced obesity, we traced the
      changes of energy balance in a wild rodent, Brandt's voles (Lasiopodomys
      brandtii), which were acclimated to either long day (16L: 8D, LD) or short day
      (8L: 16D, SD) and fed either low-fat diet (LFD) or high-fat diet (HFD) in each
      photoperiodic manipulation. We found that Brandt's vole was not resistant to high
      fat diet-induced obesity and SD, not HFD, induced the elevation in basal
      metabolic rate, the maximal rate of oxygen consumption after norepinephrine
      injection, and uncoupling protein 1 content in brown adipose tissue. HFD caused
      the increase in apparent digestibility and body fat mass, and the decrease in
      energy intake in both LD and SD voles. The enhancement of energy absorption
      associated with small intestine tissue recruitment can compensate the lower
      energy intake, which may contribute to the high-fat diet-induced body fat
      deposition. Thus, a decrease in body-weight gain but has no resistance to high
      fat induced obesity implies an evolutionary and adaptive mechanism which is a
      benefit for their winter survival.

PMID- 19840810
TI  - Cost of digging is determined by intrinsic factors rather than by substrate
      quality in two subterranean rodent species.
AB  - Searching for food by extensive digging is one of the most important aspects of
      life of subterranean rodents. We studied the effect of extrinsic (substrate
      quality) and intrinsic factors (sex and body mass) upon the cost of burrowing,
      expressed as digging metabolic rate (DMR) in two African mole-rat species
      (Bathyergidae, Rodentia) with distinct social structures. The sexually dimorphic
      giant mole-rat (Fukomys mechowii) is a highly social species, whereas the almost
      monomorphic silvery mole-rat (Heliophobius argenteocinereus) is a solitary
      bathyergid. Burrowing in F. mechowii was more costly (DMR was greater) than in H.
      argenteocinereus, but there was no difference in burrowing speed between both
      species. DMR within a particular species was dependent upon body mass, but
      independent of sex. Different substrate quality had no effect upon DMR in either
      species, yet it affected burrowing speed. We conclude that less effective digging
      in F. mechowii can be compensated by the joint workforce of other family members.
      Alternatively, H. argenteocinereus, being a more effective digger, can afford a
      solitary way of life.

PMID- 19840811
TI  - Paced mating behavior persists in rats with vaginocervical Lidocaine.
AB  - The present study tested whether the topical application of a local anesthetic
      (Lidocaine) to the vaginocervical region altered the pattern of paced mating
      behavior displayed by gonadectomized, hormone-primed female rats. Both rats
      receiving Lidocaine and rats receiving vehicle exhibited the expected lengthening
      of contact-return latency as the intensity of the mating stimuli increased
      (mount<intromission<ejaculation). Although rats given Lidocaine versus vehicle
      received a greater number of intromissions, no other group differences were
      observed. The present study found no evidence for a change in behavioral
      responsiveness following the vaginocervical application of Lidocaine.

PMID- 19840812
TI  - Effects of estradiol on food intake and meal patterns for diets that differ in
      flavor and fat content.
AB  - Apart from the well known inhibitory effects of estradiol on food intake, meal
      size, and body weight in female rats that have been documented over the past
      thirty years, a more recent report presents the opposite finding; that a large
      dose of estradiol can increase food intake and weight gain in gonadally intact
      female rats presented with a palatable diet. The purpose of the present
      experiment was to further examine this hypothesis by evaluating the ability of
      estradiol to influence feeding behavior in ovariectomized rats presented with
      diets that differ in flavor and fat content. Female rats were given a cyclic
      regimen of estradiol benzoate treatment (5.0 or 20.0 microg) or the oil vehicle
      and were presented with the standard chow diet or a diet with a higher fat
      content and chocolate flavor. Food intake, meal size, and meal number were
      monitored three days after the first injection of estradiol or oil. Compared to
      the chow diet, food intake increased when animals had access to the chocolate/fat
      diet during the vehicle treatment condition. Both doses of estradiol
      significantly decreased food intake, meal size, and body weight gain when animals
      were presented with either the standard chow diet or the chocolate/fat diet.
      These findings indicate that estradiol does not stimulate the intake of a
      palatable diet in ovariectomized rats, and suggest that previous results showing
      that estradiol enhanced eating and weight gain stemmed from a disruption of the
      hypothalamic-pituitary-gonadal axis when intact females received a large dose of
      exogenous estradiol.

PMID- 19840813
TI  - Unique biomechanical interactions between myeloma cells and bone marrow stroma
      cells.
AB  - We observed that BMSCs (bone marrow stromal cells) from myeloma patients (myeloma
      BMSCs) were significantly stiffer than control BMSCs using a cytocompression
      device. The stiffness of myeloma BMSCs and control BMSCs was further increased
      upon priming by myeloma cells. Additionally, myeloma cells became stiffer when
      primed by myeloma BMSCs. The focal adhesion kinase activity of myeloma cells was
      increased when cells were on stiffer collagen gels and on myeloma BMSCs. This
      change in myeloma stiffness is associated with increased colony formation of
      myeloma cells and FAK activation when co-cultured with stiffer myeloma BMSCs or
      stiffer collagen. Additionally, stem cells of RPMI8226 cells became stiffer after
      priming by myeloma BMSCs, with concomitant increases of stem cell colony
      formation. These results suggest the presence of a mechanotransduction loop
      between myeloma cells and myeloma BMSCs to increase the stiffness of both types
      of cells via FAK activation. The increase of stiffness may in turn support the
      growth of myeloma cells and myeloma stem cells.

PMID- 19840814
TI  - Markers of squamous cell carcinoma in sarco/endoplasmic reticulum Ca2+ ATPase 2
      heterozygote mice keratinocytes.
AB  - A mutation of Atp2a2 gene encoding the sarco/endoplasmic reticulum Ca(2+)-ATPase
      2 (SERCA2) causes Darier's disease in human and null mutation in one copy of
      Atp2a2 leads to a high incidence of squamous cell tumor in a mouse model. In
      SERCA2 heterozygote (SERCA2(+/-)) mice keratinocytes, mechanisms involved in
      partial depletion of SERCA2 gene and its related tumor induction have not been
      studied. In this study, we investigated Ca(2+) signaling and differential gene
      expression in primary cultured keratinocytes from SERCA2(+/-) mice. SERCA2(+/-)
      keratinocytes showed reduced initial increases in intracellular concentration of
      calcium in response to ATP, a G-protein coupled receptor agonist, and higher
      store-operated Ca(2+) entry with the treatment of thapsigargin, an inhibitor of
      SERCA, compared to wild type kerationcytes. Protein expressions of plasma
      membrane Ca(2+) ATPases, NFATc1, phosphorylated ERK, JNK, and phospholipase
      gamma1 were increased in SERCA2(+/-) keratinocytes. Using the gene fishing
      system, we first found in SERCA2(+/-) keratinocytes that gene level of tumor
      associated calcium signal transducer 1, crystalline alphaB, procollagen XVIII
      alpha1, and nuclear factor I-B were increased. Expression of involucrin, a marker
      of keratinocyte differentiation, was decreased in SERCA2(+/-) keratinocytes.
      These results suggest that the alterations of Ca(2+) signaling by SERCA2
      haploinsufficiency alternate the gene expression of tumor induction and
      differentiation in keratinocytes.

PMID- 19840815
TI  - Acute nicotine and phencyclidine increase locomotor activity of the guinea pig
      with attenuated potencies relative to their effects on rat or mouse.
AB  - Behavioral assays of the responses to psychomotor stimulants can be used to model
      certain aspects of CNS pathologies such as psychosis and addiction. However,
      species-dependent differences in the effects of neuromodulators in these assays
      can confound the interpretation of the results. The goal of this study was to
      determine the utility of the guinea pig as a model for assessing the behavioral
      actions of nicotinic receptor agonists and NMDA receptor antagonists. In the
      present study, the locomotor activity of adult male guinea pigs was measured,
      prior to and following an acute injection of nicotine, MK-801 or phencyclidine.
      Each animal received a single dose of the drug. Nicotine produced a dose
      dependent increase in activity with an ED(50) of 1.5mg/kg. Phencyclidine also
      increased activity, with an ED(50) of 3.4 mg/kg. Nicotine produced increases in
      locomotion in all individual subjects tested, whereas at the maximally-effective
      dose of phencyclidine, only a fraction of the animals had locomotor activation.
      There was no change in activity in response to a single dose of MK-801
      (0.5mg/kg). Haloperidol had a significant inhibitory effect on locomotor activity
      independent of the stimulant administered. Thus, both phencyclidine and nicotine
      are psychomotor stimulants when given to guinea pigs, although the intensity of
      the response and the potencies of these drugs are lower than in mice or rats
      under otherwise similar conditions.

PMID- 19840817
TI  - An economic evaluation of health-promotive built environment changes.
AB  - OBJECTIVES: This study aimed to help public investment decision makers see the
      greatest return on their built environment investments by developing an analysis
      framework for identifying the most promising improvement strategies and assessing
      the attainable return on investment. METHODS: The 2001 National Household Travel
      Survey sample (N=4974) from Dane County, Wisconsin, was used to develop a Spatial
      Seemingly Unrelated Regression model of daily vehicle miles traveled and miles
      walked or biked. The empirical model was used to analyze the travel impacts of
      hypothetical built environment changes. These travel impacts were translated into
      health impacts and monetary values using cost-benefit analysis. RESULTS: Two win
      win built environment strategies were found: increased regional retail
      accessibility and increased prevalence of sidewalks. Based on the present
      analyses, an investment of $450 million to make sidewalks available to all Dane
      County residents was estimated to yield a cost-benefit ratio of 1.87 over a 10
      year life cycle. CONCLUSION: Certain built environment measures could be
      predicted to be effective strategies for exerting a positive influence on
      people's travel behavior and the health of the community. Quantifiable public
      health benefits gained by better air quality and increased physical activity were
      shown to outweigh the cost of implementing the built environment measure of
      adding sidewalks to all roads.

PMID- 19840816
TI  - Allopregnanolone, the active metabolite of progesterone protects against neuronal
      damage in picrotoxin-induced seizure model in mice.
AB  - Progesterone exerts anti-seizure effect against several chemoconvulsants.
      However, there is no published report on the interaction between progesterone and
      picrotoxin (PTX). The present study evaluated the effects of progesterone and its
      active metabolite, allopregnanolone against PTX-induced seizures, brain lipid
      peroxidation and DNA fragmentation in male mice. Finasteride, a 5alpha-reductase
      inhibitor and indomethacin, an inhibitor of 3infinity-hydroxysteroid
      dehydrogenase were assessed against progesterone's effects on PTX-induced
      seizures, brain lipid peroxidation and DNA fragmentation. PTX produced clonic
      tonic seizures in mice with CD50 and CD97 of 2.4 and 4.0mg/kg, i.p. respectively.
      Progesterone significantly countered PTX-induced seizures, with ED50 of
      78.30mg/kg and ED97 of 200mg/kg. Progesterone antagonized PTX-induced DNA
      fragmentation. Finasteride (200mg/kg) and indomethacin (1mg/kg) reversed the anti
      seizure and anti-DNA fragmentation effects of progesterone. Allopregnanolone,
      also protected against PTX-induced seizures and DNA fragmentation. There was no
      significant change in the brain lipid peroxidation parameters in any of the
      treatment groups. It may be concluded that progesterone protects against PTX
      induced seizures and DNA fragmentation through its active metabolites
      allopregnanolone and 5alpha-pregnan-3,20-dione. However, it appears from the
      present study that, the neuroprotection with progesterone is primarily on account
      of allopregnalone. The therapeutic potential of allopregnanolone deserves to be
      evaluated clinically.

PMID- 19840818
TI  - Serial knife stabbings with HIV exposure--implications for post-exposure
      prophylaxis.
AB  - Thirty-three persons became victims of a serial knife stabbing incident. One of
      the first victims one day later disclosed that he was HIV-infected. Thereafter
      thirty-one victims initiated HIV post-exposure prophylaxis (PEP), one exposed
      patient declined. None of the victims evaluated had seroconverted six months
      later. In most such incidents HIV exposure will be difficult to rule out as
      reliable information on the HIV serostatus of all serial victims will be lacking.
      It appears prudent, however, to inform serial stab victims about the potential
      risk of HIV transmission and to at least consider PEP in such scenarios.

PMID- 19840819
TI  - Acute SSRI-induced anxiogenic and brain metabolic effects are attenuated 6 months
      after initial MDMA-induced depletion.
AB  - To assess the functional state of the serotonergic system, the acute behavioural
      and brain metabolic effect of SSRI antidepressants were studied during the
      recovery period after MDMA-induced neuronal damage. The effects of the SSRI
      fluoxetine and the serotonin receptor agonist meta-chloro-phenylpiperazine (m
      CPP) were investigated in the social interaction test in Dark Agouti rats, 6
      months after treatment with a single dose of MDMA (15 or 30 mg kg(-1), i.p.). At
      earlier time points these doses of MDMA have been shown to cause 30-60% loss in
      axonal densities in several brain regions. Densities of the serotonergic axons
      were assessed using serotonin-transporter and tryptophan-hydroxylase
      immunohistochemistry. In a parallel group of animals, brain function was examined
      following an acute challenge with either fluoxetine or citalopram, using 2
      deoxyglucose autoradiographic imaging. Six months after MDMA treatment the
      densities of serotonergic axons were decreased in only a few brain areas
      including hippocampus and thalamus. Basal anxiety was unaltered in MDMA-treated
      animals. However, the acute anxiogenic effects of fluoxetine, but not m-CPP, were
      attenuated in animals pretreated with MDMA. The metabolic response to both
      citalopram and fluoxetine was normal in most of the brain areas examined with the
      exception of ventromedial thalamus and hippocampal sub-fields where the response
      was attenuated. These data provide evidence that 6 months after MDMA-induced
      damage serotonergic axons show recovery in most brain areas, but serotonergic
      functions to challenges with SSRIs including anxiety and aggression remain
      altered.

PMID- 19840820
TI  - Baclofen enhances extinction of opiate conditioned place preference.
AB  - Conditioned opiate reward (COR) is rapidly acquired and slowly extinguished. The
      slow rate of extinction of the salience of drug-related cues contributes to drug
      craving and relapse. The gamma-aminobutyric acid receptor type B (GABA(B))
      agonist, baclofen, attenuates the unconditioned rewarding actions of several
      drugs of abuse and was investigated for effects on the extinction of COR. C57BL/6
      mice were utilized in an unbiased conditioned place preference (CPP) protocol
      using morphine (10mg/kg, s.c.) and saline. CPP was measured by increases in time
      spent in the morphine-associated (CS+) vs. the saline-associated (CS-) chamber in
      a 15-min test after four morphine and four saline alternated conditioning
      sessions. CPP and locomotor sensitization were produced to the CS+ chamber.
      Subsequently, sixteen daily extinction sessions were conducted with either
      vehicle or baclofen (1 or 2.5mg/kg, s.c.) treatment given either before or after
      the sessions. This design was used to create the baclofen drug state before or
      after the activation of the CPP memory trace in the extinction protocol. After
      morphine CPP development, its extinction was significantly facilitated in a dose
      dependent manner by post-session, but not by pre-session, baclofen treatments. No
      significant sedative effects of baclofen were detected during any extinction
      training or testing phase. Baclofen treatment facilitated the extinction of COR
      and reduced conditioned sensitization during extinction when given after, but not
      before, the activation of the CPP memory trace. Baclofen appears to have
      disrupted reconsolidation of conditioned reward memory during extinction training
      and might similarly facilitate extinction learning in human opiate addiction.

PMID- 19840821
TI  - Methotrexate reduces hippocampal blood vessel density and activates microglia in
      rats but does not elevate central cytokine release.
AB  - Methotrexate is a cytostatic drug applied in adjuvant chemotherapy and associated
      with cognitive impairment in part of the cancer patients. In this paper we
      studied in rats whether a reduction in blood supply to the brain or
      neuroinflammation are possible mediators of this cognitive dysfunctionality.
      Methotrexate reduced hippocampal blood vessel density 1 week and 3 weeks after
      treatment as measured immunohistochemically with an endothelial barrier antigen.
      Since reduced brain vascularization may relate to lowered central glucose
      metabolism [(18)F]FDG PET was performed. Methotrexate reduced tracer uptake in
      the hippocampal region 1 week after treatment, which was not seen 3 weeks after
      treatment. Neuroinflammatory processes were explored via a number of methods: a
      microglia immunohistochemical marker was applied to hippocampal sections,
      [(11)C]PK11195 PET was performed, and cytokine levels in plasma and homogenized
      hippocampal tissue were measured. Methotrexate activated microglia in the
      hippocampus 1 week and 3 weeks after treatment. PET analysis, however, did not
      show an increase in hippocampal tracer uptake and the multiplex analysis of
      various cytokines showed that hippocampal cytokine levels were not increased
      after methotrexate administration. Methotrexate did reduce plasma cytokine levels
      indicating a suppression of peripheral immune functioning. Methotrexate reduces
      hippocampal blood vessel density, indicative of a reduced brain glucose
      metabolism, which may contribute to the cognitive impairment following
      methotrexate administration. Although methotrexate activates microglia activation
      in the hippocampus, no effects were seen in [(11)C]PK11195 tracer uptake or
      hippocampal cytokine levels. This suggests that the microglial activation in this
      study is not a marker for neuroinflammation.

PMID- 19840822
TI  - Abnormal inhibitory processes in semantic networks in schizophrenia.
AB  - Abnormal language in schizophrenia has been regarded as a hallmark of this
      disorder. Language abnormalities include loose and unusual associations,
      tangentiality, and inability to maintain a topic. Recent theories of language
      dysfunction have invoked working memory abnormalities, as well as abnormal
      processes within semantic memory in schizophrenia. Two views, often construed as
      opposing, have been offered to account for language peculiarities in
      schizophrenia: one holds that initial processes of activation are abnormal while
      the other holds that late processes of context utilization might be disturbed. We
      suggest that these views may be complementary rather than mutually exclusive.
      Given the relative paucity of data on the early processes within semantic
      networks, we present new evidence using ERP short SOA paradigm that these
      processes are abnormal in schizophrenia. Furthermore, reduced N400 in the
      unrelated condition found in this study suggests that the abnormality was related
      to inefficient early inhibitory processes.

PMID- 19840823
TI  - Spray drying of siRNA-containing PLGA nanoparticles intended for inhalation.
AB  - Local delivery of small interfering RNA (siRNA) to the lungs constitutes a
      promising new area in drug delivery. The present study evaluated parameters of
      importance for spray drying of siRNA-loaded poly(D,L-lactide-co-glycolide) (PLGA)
      nanoparticles (NPs) into nanocomposite microparticles intended for inhalation.
      The spray drying process was optimised using a statistical design of experiment
      and by evaluating powder characteristics upon systematic variation of the
      formulation parameters. Concentration, carbohydrate excipient (trehalose, lactose
      and mannitol) and the ratio of NP to excipient were varied to monitor the effects
      on moisture content, particle morphology, particle size and powder yield. The
      identified optimum conditions were applied for spray drying of siRNA-loaded
      nanocomposite microparticles, resulting in a product with a low water content
      (0.78% w/w) and an aerodynamic particle diameter considered suitable for
      inhalation. The use of mannitol in the formulation allowed a significantly lower
      moisture content than trehalose and lactose. The inclusion of 50% (w/w) or higher
      amounts of NPs resulted in a marked change in the surface morphology of the spray
      dried particles. Importantly, the integrity and biological activity of the siRNA
      were preserved during the spray drying process. In conclusion, the present
      results show that spray drying is a suitable technique for producing
      nanocomposite microparticles comprising siRNA-containing PLGA NPs for potential
      use in inhalation therapy.

PMID- 19840824
TI  - Cationic amphiphilic polyproline helix P11LRR targets intracellular mitochondria.
AB  - We demonstrate that P11LRR, a recently developed amphiphilic polyproline, cell
      penetrating agent, is able to locate inside the mitochondria of various cell
      lines when administrated at high concentrations. Mitochondrial targeting was
      verified by confocal fluorescence co-localization of P11LRR-fluorescein with
      Mitotracker Red. Elimination of mitochondrial membrane potential dramatically
      inhibits the localization of P11LRR to mitochondria. Concentration-dependency
      experiments suggest that cellular internalization of P11LRR occurs via two
      different pathways: endocytosis and direct transport. Results indicate that the
      latter pathway predominates at high concentrations of P11LRR, resulting in
      localization of the agent to the mitochondria. The membrane translocation pathway
      was further confirmed by two endocytosis inhibitors, cytochalasin D and
      phenylarsine oxide, and by modulation of plasma membrane potential. The potential
      of using P11LRR as a mitochondrial drug delivery vector was demonstrated through
      the delivery of a covalently linked small antioxidant, dimethyltyrosine (Dmt),
      which allowed for the reduction of chemically induced reactive oxygen species
      within the mitochondria.

PMID- 19840826
TI  - Quantitative cancer risk assessment based on NIOSH and UCC epidemiological data
      for workers exposed to ethylene oxide.
AB  - The most recent epidemiological data on individual workers in the NIOSH and
      updated UCC occupational studies have been used to characterize the potential
      excess cancer risks of environmental exposure to ethylene oxide (EO). In addition
      to refined analyses of the separate cohorts, power has been increased by
      analyzing the combined cohorts. In previous SMR analyses of the separate studies
      and the present analyses of the updated and pooled studies of over 19,000
      workers, none of the SMRs for any combination of the 12 cancer endpoints and six
      sub-cohorts analyzed were statistically significantly greater than one including
      the ones of greatest previous interest: leukemia, lymphohematopoietic tissue,
      lymphoid tumors, NHL, and breast cancer. In our study, no evidence of a positive
      cumulative exposure-response relationship was found. Fitted Cox proportional
      hazards models with cumulative EO exposure do not have statistically significant
      positive slopes. The lack of increasing trends was corroborated by categorical
      analyses. Cox model estimates of the concentrations corresponding to a 1-in-a
      million extra environmental cancer risk are all greater than approximately 1ppb
      and are more than 1500-fold greater than the 0.4ppt estimate in the 2006 EPA
      draft IRIS risk assessment. The reasons for this difference are identified and
      discussed.

PMID- 19840825
TI  - Formulation and coating of microneedles with inactivated influenza virus to
      improve vaccine stability and immunogenicity.
AB  - Microneedle patches coated with solid-state influenza vaccine have been developed
      to improve vaccine efficacy and patient coverage. However, dip coating
      microneedles with influenza vaccine can reduce antigen activity. In this study,
      we sought to determine the experimental factors and mechanistic pathways by which
      inactivated influenza vaccine can lose activity, as well as develop and assess
      improved microneedle coating formulations that protect the antigen from activity
      loss. After coating microneedles using a standard vaccine formulation, the
      stability of influenza vaccine was reduced to just 2%, as measured by
      hemagglutination activity. The presence of carboxymethylcellulose, which was
      added to increase viscosity of the coating formulation, was shown to contribute
      to vaccine activity loss. After screening a panel of candidate stabilizers, the
      addition of trehalose to the coating formulation was found to protect the antigen
      and retain 48-82% antigen activity for all three major strains of seasonal
      influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited
      thermal stability, such that activity loss was independent of temperature over
      the range of 4-37 degrees C for 24h. Dynamic light scattering measurements showed
      that antigen activity loss was associated with virus particle aggregation, and
      that stabilization using trehalose largely blocked this aggregation. Finally,
      microneedles using an optimized vaccine coating formulation were applied to the
      skin to vaccinate mice. Microneedle vaccination induced robust systemic and
      functional antibodies and provided complete protection against lethal challenge
      infection similar to conventional intramuscular injection. Overall, these results
      show that antigen activity loss during microneedle coating can be largely
      prevented through optimized formulation and that stabilized microneedle patches
      can be used for effective vaccination.

PMID- 19840827
TI  - Estimation of honey authenticity by multielements characteristics using
      inductively coupled plasma-mass spectrometry (ICP-MS) combined with chemometrics.
AB  - In our study the mineral content of 55 honey samples, which represented three
      different types of honey: honeydew, buckwheat and rape honey from different areas
      in Poland, was evaluated. Determination of 13 elements (Al, B, Ba, Ca, Cd, Cu, K,
      Mg, Mn, Na, Ni, Pb, Zn) was performed using inductively coupled plasma-mass
      spectrometry. We tried to prove that the analysis of quality and quantity of
      honey elements could be used to define honey origin by using ICP-MS as a
      technique for simultaneous determination of elements. Chemometric methods, such
      as CA and PCA, were applied to classify honey according to mineral content. CA
      showed three clusters corresponding to the three botanical origins of honey. PCA
      permitted the reduction of 13 variables to four principal components explaining
      77.19% of the total variance. The first most important principal component was
      strongly associated with the value of K, Al, Ni and Cd. This study revealed that
      CA and PCA analysis appear useful tools for differentiation of honey samples
      authenticity using the profile of mineral content and they highlighted the
      relationship between the elements distribution and honey type.

PMID- 19840828
TI  - Effects of Areca catechu L. containing procyanidins on cyclooxygenase-2
      expression in vitro and in vivo.
AB  - Polyphenols are widely distributed in plants and known for antioxidant and anti
      inflammatory properties. Areca nut, rich in polyphenols, is the major component
      of betel quid and we have previously shown that the extract of areca nut can
      induce oxidative stress in vitro. In this study, we have further pinpointed that
      areca nut extract (ANE) contains catechin based procyanidins which range from
      dimers to decamers and polymers; this was carried out by HPLC and electrospray
      ionization/mass spectrometry (ESI/MS). To quantify their antioxidant potential,
      oligomeric and polymeric procyanidins of ANE were separated and evaluated using
      the Trolox equivalent antioxidant capacity (TEAC) assay. The results clearly
      demonstrated that the antioxidant capacity of the ANE procyanidins increased with
      the degree of polymerization. The anti-inflammatory potential of ANE was also
      tested using 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated human oral cancer
      SAS cells. ANE inhibited TPA-induced cyclooxygenase-2 (COX-2) protein expression
      at low doses, which correlated with the inhibition of ERK phosphorylation in the
      SAS cells. Furthermore, feeding rats with ANE at 1 and 10mg/kg/day for 5days
      significantly repressed carrageenan-induced inflammatory exudates and PGE(2)
      formation. In conclusion, ANE, which contains catechins based oligomeric and
      polymeric procyanidins, regulates COX-2 expression in vitro and possess anti
      inflammatory potential in vivo.

PMID- 19840829
TI  - Three-year clinical evaluation of a flowable and a hybrid resin composite in non
      carious cervical lesions.
AB  - OBJECTIVES: This randomized controlled clinical trial evaluated the 3-year
      clinical performance of a hybrid (Clearfil AP-X; AP) and a flowable (Clearfil
      Flow FX; FX) resin composite in 98 non-carious cervical lesions. METHODS: Twenty
      two patients, 11 males and 11 females (mean age: 61.9 years, range: 29-78 years)
      regularly visiting the Nagasaki University Hospital, participated in the study.
      Each patient received both materials randomly. All restorations (48 restorations
      for AP and 50 restorations for FX) were placed in conjunction with an all-in-one
      system (Clearfil S(3) Bond) by one dentist. The restorations were blindly
      evaluated by two examiners at baseline, 6 months, 1, 2 and 3 years using modified
      USPHS criteria. The data were statistically analyzed using the Cochran's Q-test
      and Fisher's exact test. RESULTS: All the patients were examined at each recall.
      However, five restorations could not be evaluated at 3-year recall as two teeth
      had been extracted and three restorations had been lost. The only minor problem
      was the integrity of the enamel margin. The incidence and extent of marginal
      staining increased with time, but it was still superficial. Marginal staining
      occurred adjacent to 11 restorations for AP and 12 restorations for FX after 3
      years. Neither lesion size nor depth had influence on marginal staining adjacent
      to each type of resin composite. There were no significant differences in the
      clinical performances between AP and FX for each variable. CONCLUSIONS: Under the
      protocol used in this study, both types of resin composite in conjunction with
      S(3) Bond demonstrated an acceptable clinical performance up to 3 years.

PMID- 19840830
TI  - Age-related changes in postural control sensory reweighting.
AB  - The aim of this study was to investigate the adaptive process in the coupling
      between visual information and body sway in children postural control. Twenty
      seven children from 4-, 8- and 12-year-olds and ten adults stood upright inside
      of a moving room. In the first 2 min, the room was moved continuously at
      frequency of 0.2 Hz, velocity of 0.6 cm/s and amplitude of 0.5 cm. In the minute
      subsequent the room was moved with velocity of 3.5 and amplitude of 3.2 and in
      the last 2 min with velocity of 0.6 cm/s and amplitude of 0.5 cm. Gain, phase,
      SFSA and transient gain were used to examine the relationship between sensory
      information and body sway. The results showed that children and adults were
      capable to adapt to the changes of visual stimulus, downweighting the visual
      information influences when the room's amplitude/velocity increased. However, the
      young children did not show calibrated response to the 12-year-old children and
      adults level, being more influenced by the visual stimulus.

PMID- 19840831
TI  - Environmental enrichment reduces mechanical hypersensitivity in neuropathic mice,
      but fails to abolish the phenotype of CCK2 receptor deficient mice.
AB  - Genetic invalidation of CCK(2) receptors abolishes chronic constriction injury
      (CCI) induced mechanical hypersensitivity in mice. However, housing in
      environmentally enriched conditions significantly alters the phenotype of CCK(2)
      receptor deficient mice in all major behavioral domains. Furthermore,
      environmental enrichment itself has been reported to have protective effects in
      several rodent models of neurological diseases (brain and spinal trauma, ischemic
      stroke, Alzheimer's disease, etc.). In the present study we reproduced the
      earlier finding that mice, lacking CCK(2) receptors (-/-) are resistant to CCI
      induced hypersensitivity. On the other hand, environmental enrichment
      substantially reduced CCI-induced mechanical hypersensitivity in wild-type (+/+)
      mice. Nevertheless, the phenotypic differences between wild-type (+/+) and mutant
      (-/-) mice in mechanical sensitivity before and after CCI-surgery were not
      eliminated by alternative housing conditions. These observations suggest that
      environmental enrichment has beneficial effects in neuropathic conditions and
      reinforce the causal link between CCK(2) receptors, mechanical sensitivity and
      the development of CCI-induced hypersensitivity.

PMID- 19840832
TI  - A method to describe enzyme-catalyzed reactions by combining steady state and
      time course enzyme kinetic parameters.
AB  - BACKGROUND: Complete analysis of single substrate enzyme-catalyzed reactions has
      required a separate use of two distinct approaches. Steady state approximations
      are employed to obtain substrate affinity and initial velocity information.
      Alternatively, first order exponential decay models permit simulation of the time
      course data for the reactions. Attempts to use integrals of steady state
      equations to describe reaction time courses have so far met with little success.
      METHODS: Here we use equations based on steady state approximations to directly
      model time course plots. RESULTS: Testing these expressions with the enzyme beta
      galactosidase, which adheres to classical Michaelis-Menten kinetics, produced a
      good fit between observed and calculated values. GENERAL SIGNIFICANCE: This study
      indicates that, in addition to providing information on initial kinetic
      parameters, steady state approximations can be employed to directly model time
      course kinetics. Integrated forms of the Michaelis-Menten equation have
      previously been reported in the literature. Here we describe a method to directly
      apply steady state approximations to time course analysis for predicting product
      formation and simultaneously obtain multiple kinetic parameters.

PMID- 19840833
TI  - Mannose binding lectin and lung collectins interact with Toll-like receptor 4 and
      MD-2 by different mechanisms.
AB  - BACKGROUND: We have previously shown that lung collectins, surfactant protein A
      (SP-A) and surfactant protein D, interact with Toll-like receptor (TLR) 2, TLR4,
      or MD-2. Bindings of lung collectins to TLR2 and TLR4/MD-2 result in the
      alterations of signaling through these receptors, suggesting the immunomodulatory
      functions of lung collectins. Mannose binding lectin (MBL) is another collectin
      molecule which has structural homology to SP-A. The interaction between MBL and
      TLRs has not yet been determined. METHODS: We prepared recombinant MBL, and
      analyzed its bindings to recombinant soluble forms of TLR4 (sTLR4) and MD-2.
      RESULTS: MBL bound to sTLR4 and MD-2. The interactions were Ca2+-dependent and
      inhibited by mannose or monoclonal antibody against the carbohydrate-recognition
      domain of MBL. Treatment of sTLR4 or MD-2 by peptide N-glycosidase F
      significantly decreased the binding of MBL. SP-A bound to deglycosylated sTLR4,
      and this property did not change in chimeric molecules of SP-A/MBL in which
      Glu195-Phe228 or Thr174-Gly194 of SP-A were replaced with the corresponding MBL
      sequences. GENERAL SIGNIFICANCE: These results suggested that MBL binds to TLR4
      and MD-2 through the carbohydrate-recognition domain, and that oligosaccharide
      moieties of TLR4 and MD-2 are important for recognition by MBL. Since our
      previous studies indicated that lung collectins bind to the peptide portions of
      TLRs, MBL and lung collectins interact with TLRs by different mechanisms. These
      direct interactions between MBL and TLR4 or MD-2 suggest that MBL may modulate
      cellular responses by altering signals through TLRs.

PMID- 19840834
TI  - Thalamic afferent activation of supragranular layers in auditory cortex in vitro:
      a voltage sensitive dye study.
AB  - We studied auditory thalamocortical interactions in vitro, using an auditory
      thalamocortical brain slice preparation. Cortical activity evoked by electrical
      stimulation of the medial geniculate nucleus (MGN) was investigated through field
      potential recordings and voltage sensitive dyes. Experiments were performed in
      slices obtained from adult mice (9-14 weeks). Stimulus evoked activity was
      detected in the granular and supragranular layers after a short latency (5-6 ms).
      In 9-14 weeks old mice infragranular activity was detected in 10 of 24
      preparations and was found to be increased in younger mice (p 31-64). In 14 of 24
      slices a prominent horizontal spread was observed, which extended into cortical
      areas lateral to A1. In these experiments, the shortest onset latencies and
      largest signal amplitudes were located in the supragranular layers of A1. In
      areas lateral to A1, shortest onset latencies were located in the granular layer,
      while largest signal amplitudes were found in the supragranular layers. Evoked
      cortical activity was sensitive to removal of extracellular Ca(2+) or application
      of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). Short repetitive
      stimulation, resembling thalamic burst activity (three pulses at 100 Hz),
      resulted in an increase of signal amplitude and excited area by approximately
      25%, without changing the overall spatiotemporal activity profile. Blockade of N
      methyl-D-aspartate receptors by 2-amino-5-phosphonopentanoate (AP5, 50 microM)
      reduced amplitudes and excited area by approximately 15-30%, irrespective of
      stimulation frequency. Application of bicuculline (10 microM) greatly increased
      cortical responses to thalamic stimulation. Under these conditions, evoked
      activity displayed a pronounced horizontal spread in combination with a 2-3-fold
      increase in amplitude. In conclusion, afferent thalamic inputs primarily activate
      supragranular and granular layers in the auditory cortex of adult mice. This
      activation is predominantly mediated by non-NMDA receptors, while GABA(A)
      receptor-mediated inhibition limits the horizontal and vertical spread of
      activity.

PMID- 19840835
TI  - One-step identification of conserved miRNAs, their targets, potential
      transcription factors and effector genes of complete secondary metabolism
      pathways after 454 pyrosequencing of calyx cDNAs from the Labiate Salvia sclarea
      L.
AB  - The outermost floral whorl, composed of sepals, is generally thought to function
      in the protection of reproductive tissues. In the plant family Lamiaceae, sepals
      are fused into a tube that is densely covered by hairs for mechanical defence and
      contains secondary metabolites for chemical defence against insects and abiotic
      stresses. Despite the importance of this tissue in plant fitness, virtually no
      study has addressed the basic aspects of sepal development and functioning.
      Because of its large size and its impressive metabolic activity (both in terms of
      quantity and diversity of secondary metabolites), we have used clary sage calyx
      as a model system to generate the first high throughput sequencing of the
      transcriptome of an angiosperm calyx. We applied massive parallel 454
      pyrosequencing technology to a normalized cDNA extract and unveiled potential
      candidate genes for all steps of secondary metabolite pathways (phenylpropanoids
      and terpenoids). It also proved efficient in predicting the expression of large
      numbers of transcription factors and, with the use of bioinformatics tools, it
      predicted in the same sequencing run the presence of a novel class of gene
      transcription regulatory elements, miRNAs, without the need to generate a
      separate miRNA library. In our clary sage EST library, 18 conserved miRNAs were
      predicted. Among them, 15 were present in most studied plant species while the
      others were only shared with limited or discrete plant lineages. A separate data
      mining of the same clary sage EST library suggested the presence of 19 potential
      target genes to the 18 predicted conserved miRNAs. These coded for only 6
      transcription factors or F-box proteins, 11 metabolism or abiotic stress response
      related proteins and 2 products with no known predicted function. All in all,
      this study provides novel genomic information on an angiosperm calyx and an
      experimental framework to predict in a single step metabolic pathway enzymes and
      regulator genes including miRNAs.

PMID- 19840836
TI  - Screening of human gene promoter activities using transfected-cell arrays.
AB  - Promoters are the best characterized transcriptional regulatory sequences in
      complex genomes because of their predictable location immediately upstream of
      transcription start sites. Despite a substantial body of literature describing
      transcriptional promoters, the identification of true start sites for all human
      transcripts is far from complete. The same is true of the key structural and
      functional elements responsible for promoter action in different cell types. In
      order to identify elements responsible for promoter activity, we applied
      transfected-cell array technology to functionally evaluate promoters for genes
      involved in inflammatory bowel disease. Seventy-four promoters were examined by
      reverse transfection of a promoter-fluorescent reporter constructs into a human
      embryonic kidney cell line (HEK293T). Sixteen (21.6%) promoters were found to be
      active in HEK293 T cells. Correlations between promoter activity and endogenous
      transcript level were calculated, and 75% of active promoters were found to be
      associated with transcriptional activity of their gene counterparts. These
      results provide experimental evidence of promoter activity, which may aid in
      understanding the regulation of gene expression. Moreover, this is the first
      large-scale functional study of regulatory sequences to use a high-throughput
      transfected-cell array technique.

PMID- 19840837
TI  - Di-(2-ethylhexyl) phthalate enhances skin sensitization to isocyanate haptens in
      mice.
AB  - Toxicological and epidemiological studies have suggested the involvement of di-(2
      ethylhexyl) phthalate (DEHP) in increases in allergies. The effects of DEHP have
      been implicated in the deflection to T helper 2 (Th2)-biased immune responses.
      However, we could not observe an adjuvant effect of DEHP in a Th2-dominant
      fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse
      model when applied epicutaneously together with a hapten. In the present study,
      we focused whether there is a hapten to which DEHP exhibits an adjuvant effect
      through the epicutaneous route. BALB/c mice were epicutaneously sensitized with 2
      methoxy-4-nitrophenyl isocyanate (MNICN) or phenethyl isocyanate (PEICN) in the
      presence or absence of phthalate esters of various kinds including DEHP. After
      challenge with a respective hapten, the ear-swelling response was measured to
      determine the level of hapten sensitization. Sensitization to MNICN and PEICN was
      enhanced when DEHP was present in the vehicle for the hapten preparation. The
      enhancement of sensitization to MNICN was accompanied by an elevated production
      of interferon-gamma and reduced production of interleukin-4 (IL-4), suggesting
      polarization to a T helper 1 (Th1)-dominant response. The results suggested that
      the combination of a hapten and a phthalate ester significantly affects the
      outcome of CHS.

PMID- 19840838
TI  - The effect of dietary polyphenols on the epigenetic regulation of gene expression
      in MCF7 breast cancer cells.
AB  - The CpG island methylator phenotype is characterized by DNA hypermethylation in
      the promoters of several suppressor genes associated with the inactivation of
      various pathways involved in tumorigenesis. DNA methylation is catalyzed by
      specific DNA methyltransferases (DNMTs). Dietary phytochemicals particularly
      catechol-containing polyphenols were shown to inhibit these enzymes and
      reactivate epigenetically silenced genes. The aim of this study was to evaluate
      the effect of a wide range of dietary phytochemicals on the activity and
      expression of DNMTs in human breast cancer MCF7 cell line and their effect on DNA
      and histone H3 methylation. All phytochemicals inhibited the DNA
      methyltransferase activity with betanin being the weakest while rosmarinic and
      ellagic acids were the most potent modulators (up to 88% inhibition). While
      decitabine led to a partial demethylation and reactivation of the genes, none of
      the tested phytochemicals affected the methylation pattern or the expression of
      RASSF1A, GSTP1 or HIN1 in MCF7 cells. The global methylation of histone H3 was
      not affected by any of the tested phytochemicals or decitabine. The results of
      our study may suggest that non-nucleoside agents are not likely to be effective
      epigenetic modulators, in our experimental model at least. However, a long-term
      exposure to these chemicals in diet might potentially lead to an effect, which
      can be sufficient for cancer chemoprevention.

PMID- 19840839
TI  - "Smart" alginate-hydroxypropylcellulose microbeads for controlled release of
      heparin.
AB  - "Smart" (thermosensitive) alginate-hydroxypropylcellulose (Alg/HPC) microbeads
      for controlled release of heparin were synthesized and the release profiles at
      various temperatures and for various alginate/HPC compositions were measured.
      Microbeads of regular spherical shape (ca. 3 microm in diameter) containing
      efficiently encapsulated heparin were obtained using an emulsification method.
      The internal structure of the bead was estimated by fluorescence microscopy using
      dansyl alginate as a labelled component. The microbeads surface structure and
      morphology were imaged in a dry state using scanning electron microscopy (SEM)
      and in water using atomic force microscopy (AFM). The microbead surface was shown
      to be covered by the regular network of pores with a mesh of ca. 30-60 nm. Lower
      critical solution temperature (LCST) of the Alg/HPC systems was measured
      spectrophotometrically (cloud point measurements). Heparin release profiles were
      obtained based on spectrophotometric detection of heparin complex with Azure A.
      Three-stage sustained release for at least 16 days was observed at 37 degrees C.
      This was correlated with the size of the pores present at the surface of
      microbeads. The release profile can be controlled by the temperature and
      composition of the Alg/HPC microbeads.

PMID- 19840840
TI  - Stress induces transient auditory hypersensitivity in rats.
AB  - Exposure to harsh environment induces stress reactions that increase probability
      of survival. Stress influences the endocrine, nervous and immune systems and
      affects the functioning of a variety of organs. Numerous researchers demonstrated
      that a 24-h exposure to an acoustic rodent repellent provokes stress reaction in
      exposed animals. In addition to the activated hypothalamic-pituitary-adrenal
      (HPA) axis, exposed animals had pathological reactions in the reproductive
      organs, bronchia and skin. Here, we examined the effect of above stress model on
      the auditory system of Wistar rats. We found that 24-h stress decreases the
      thresholds and increases the amplitudes of auditory brainstem responses and
      distortion product otoacoustic emissions. Resultant auditory hypersensitivity was
      transient and most pronounced between 3 and 6h post-stress, returning to control
      levels one week later. The concentration of corticosterone and tumor necrosis
      factor alpha was systemically elevated in stressed animals between 3 and 6h post
      stress, confirming the activation of the HPA axis. In addition, expression of the
      HPA-axis-associated genes: glucocorticoid receptor (GR) and hypoxia-inducible
      factor 1 alpha (Hif1a) was modulated in the auditory tissues. In detail, in the
      inferior colliculus, we found an up-regulation of GR mRNA 3h post-stress and
      continuous up-regulation of Hif1a up to 24h post-stress. In the spiral ganglion,
      we found no differences in gene expression between stressed and control animals.
      In the organ of Corti, expression of GR mRNA remained stable, whereas that of
      Hif1a was significantly down-regulated one week after stress. In addition, the
      expression of an outer hair cell marker prestin was significantly up-regulated 6h
      post-stress. We conclude that 24-h stress induces transient hypersensitivity of
      the auditory system and modulates gene expression in a tissue-specific manner.
      Stress-induced auditory hypersensitivity could have evolutionary consequence by
      giving animals an advantage of hearing better under stress conditions.

PMID- 19840841
TI  - Suppression of the acoustically evoked auditory-nerve response by electrical
      stimulation in the cochlea of the guinea pig.
AB  - There is increasing interest in the use of electro-acoustical stimulation in
      people with a cochlear implant that have residual low-frequency hearing in the
      implanted ear. This raises the issue of how electrical and acoustical stimulation
      interact in the cochlea. We have investigated the effect of electrical
      stimulation on the acoustically evoked compound action potential (CAP) in normal
      hearing guinea pigs. CAPs were evoked by tone bursts, and electric stimuli were
      delivered at the base of the cochlea using extracochlear electrodes. CAPs could
      be suppressed by electrical stimulation under various conditions. The dependence
      of CAP suppression on several parameters was investigated, including frequency
      and level of the acoustic stimulus, current level of the electric stimulus and
      the interval between electric and acoustic stimulus (EAI). Most pronounced
      suppression was observed when CAPs were evoked with high-frequency tones of low
      level. Suppression increased with current level and at high currents low
      frequency evoked CAPs could also be suppressed. Suppression was typically absent
      several milliseconds after the electric stimulus. Suppression mediated by direct
      neural responses and hair cell mediated (electrophonic) responses is discussed.
      We conclude that the high-frequency part of the cochlea can be stimulated
      electrically with little detrimental effects on CAPs evoked by low-frequency
      tones.

PMID- 19840842
TI  - Drosophila foxo acts in males to cause sexual-dimorphism in tissue-specific p53
      life span effects.
AB  - Sex-specific selective pressures are hypothesized to lead to sexually
      antagonistic gene functions that contribute to phenotypes such as aging and
      cancer. However, relatively little is known about the identity of such genes and
      possible mechanisms. Here we report that nervous system-specific over-expression
      of wild-type p53 in Drosophila caused decreased life span in males and increased
      life span in females. In contrast, tissue-general over-expression produced the
      opposite pattern: increased life span in males and decreased life span in
      females. In a foxo null background, p53 life span effects in males were reversed,
      becoming similar to the effects in females. In contrast, a Sir2 null background
      tended to reduce the magnitude of p53 effects. The data demonstrate that wild
      type p53 over-expression can regulate life span independent of foxo, and suggest
      that foxo acts in males to produce sexually antagonistic life span effects of
      p53.

PMID- 19840843
TI  - Comparative effects of drugs on P-glycoprotein expression and activity using rat
      and human trophoblast models.
AB  - The drug efflux transporter P-glycoprotein (P-gp) is an active component of the
      placental barrier which protects the fetus against maternal xenobiotics. The goal
      of the study was to compare species difference between human and rat in terms of
      susceptibility to drugs at the level of the placental barrier using in vitro
      models in order to improve translation from rat to human. Effects of selected
      drugs (Aspirin, Methadone, a Cardiovascular Proprietary Compound, Thalidomide) on
      cytotoxicity and P-gp expression and activity were compared using human and rat
      trophoblast cultures. No direct cytotoxicity of drugs on trophoblasts was noted
      in both invitro models, but for Thalidomide a proliferative effect on human
      trophoblast primocultures was observed. All tested drugs induced changes towards
      P-gp; for each drug the same profile was noted in both human and rat trophoblast
      models except for Thalidomide. Observation of this similar response between these
      two in vitro trophoblast models is promising for assessment between P-gp
      expression and activity of drugs towards placental function.

PMID- 19840844
TI  - Comparison of gene expression profiles in BALB/c 3T3 transformed foci exposed to
      tumor promoting agents.
AB  - Identification of specific etiological carcinogens is one of the most important
      issues in environmental-toxicology studies. In this study, cDNA microarrays were
      used to analyze gene expression and discern chemical-associated profiles induced
      by a variety of tumor promoting agents in transformed cells. Two-stage
      transformation model of BALB/c 3T3 cells was established with MNNG as initiator,
      and 12-O-tetradecanoylphorbol-13-acetate (TPA), okadaic acid (OA), or cadmium
      chloride (CdCl(2)) as tumor promoters. Nine morphologically transformed foci were
      isolated and the anchorage-independent growth of transformed cells was verified.
      The gene expression alterations in foci were evaluated using cDNA microarray with
      1796 mouse genes. Unsupervised hierarchical clustering analysis revealed that the
      nine foci were classified into three groups in concordance with the promoters
      used to induce them and characteristic clusters of genes were identified. In
      these clusters, genes associated with oxidative stress were specially upregulated
      following distinct promoter exposure. Moreover, common gene expression
      alterations were also observed in foci, including upregulated genes associated
      with cell proliferation and downregulated genes associated with extracellular
      matrix. Our results demonstrate the presence of unique gene expression profiles
      in transformed cells which reflect the etiological chemicals and indicate the
      importance of characteristic molecular alterations as potential biomarkers of
      exposure to tumor promoters.

PMID- 19840846
TI  - Proteomic investigation of enzymes involved in 2-ethylhexyl nitrate
      biodegradation in Mycobacterium austroafricanum IFP 2173.
AB  - 2-Ethyhexyl nitrate (2-EHN) is a synthetic chemical used as a diesel fuel
      additive, which is recalcitrant to biodegradation. In this study, the enzymes
      involved in 2-EHN degradation were investigated in Mycobacterium austroafricanum
      IFP 2173. Using two-dimensional gel electrophoresis and a shotgun proteomic
      approach, a total of 398 proteins appeared to be more abundant in cells exposed
      to 2-EHN than in acetate-grown cells. This set of proteins includes multiple
      isoenzymes of the beta-oxidation pathway, two alcohol and one aldehyde
      dehydrogenase, as well as four cytochromes P450, including one CYP153 which
      functions as an alkane hydroxylase. Strain IFP 2173 was also found to contain two
      alkB-like genes encoding putative membrane-bound alkane hydroxylases. RT-PCR
      experiments showed that the gene encoding the CYP153 protein, as well as alkB
      genes, were expressed on 2-EHN. These findings are discussed in the light of a
      recently proposed 2-EHN degradation pathway involving an initial attack by an
      alkane hydroxylase and one turn of beta-oxidation, leading to the accumulation of
      a gamma-lactone as a dead-end product.

PMID- 19840845
TI  - Ascorbate protects endothelial barrier function during septic insult: Role of
      protein phosphatase type 2A.
AB  - Endothelial barrier dysfunction contributes to morbidity in sepsis. We tested the
      hypothesis that raising the intracellular ascorbate concentration protects the
      endothelial barrier from septic insult by inhibiting protein phosphatase type 2A.
      Monolayer cultures of microvascular endothelial cells were incubated with
      ascorbate, dehydroascorbic acid (DHAA), the NADPH oxidase inhibitors apocynin and
      diphenyliodonium, or the PP2A inhibitor okadaic acid and then were exposed to
      septic insult (lipopolysaccharide and interferon-gamma). Under standard culture
      conditions that depleted intracellular ascorbate, septic insult stimulated
      oxidant production and PP2A activity, dephosphorylated phosphoserine and
      phosphothreonine residues in the tight junction-associated protein occludin,
      decreased the abundance of occludin at cell borders, and increased monolayer
      permeability to albumin. NADPH oxidase inhibitors prevented PP2A activation and
      monolayer leak, showing that these changes required reactive oxygen species.
      Okadaic acid, at a concentration that inhibited PP2A activity and monolayer leak,
      prevented occludin dephosphorylation and redistribution, implicating PP2A in the
      response of occludin to septic insult. Incubation with ascorbate or DHAA raised
      intracellular ascorbate concentrations and mitigated the effects of septic
      insult. In conclusion, ascorbate acts within microvascular endothelial cells to
      inhibit septic stimulation of oxidant production by NADPH oxidase and thereby
      prevents PP2A activation, PP2A-dependent dephosphorylation and redistribution of
      occludin, and disruption of the endothelial barrier.

PMID- 19840847
TI  - Supplement 2003-2007 (No. 47) to the White-Kauffmann-Le Minor scheme.
AB  - This supplement reports the characterization of 70 new Salmonella serovars
      recognized between 2003 and 2007 by the WHO Collaborating Center for Reference
      and Research on Salmonella: 44 were assigned to Salmonella enterica subspecies
      enterica, 11 to subspecies salamae, 5 to subspecies arizonae, 8 to subspecies
      diarizonae, one to subspecies houtenae and one to Salmonella bongori. One new
      serovar, Mygdal, displayed a new H factor, H:z(91).

PMID- 19840848
TI  - FAK mediates signal crosstalk between type II collagen and TGF-beta 1 cascades in
      chondrocytic cells.
AB  - The purpose of this study was to evaluate the mechanism of crosstalk between the
      type II collagen and TGF-beta1 signaling pathways in chondrocytic cells.
      Articular chondrocytes, isolated from porcine knee cartilage, and the SW1353 cell
      line were cultured on either type II collagen-coated or -uncoated plates in the
      presence or absence of TGF-beta1. Expression of pSMAD 2, pSMAD 3, pFAK(Y397) and
      pFAK(Y925) in articular chondrocytes and the SW1353 cell line was analyzed by
      immunoblotting. Cell proliferation rates and glycosaminoglycan (GAG) content was
      determined after treatment with type II collagen or/and TGF-beta1. For inhibition
      study, human FAK-specific RNA small interference (siFAK) in SW1353 cell line was
      performed. In this study, expression of pSMAD 2, pSMAD 3, pFAK(Y397) and
      pFAK(Y925) were synergistically increased by co-treatment with type II collagen
      and TGF-beta1 in articular chondrocytes. The proliferation of porcine articular
      chondrocytes and GAG secretion in SW1353 cells were synergistically increased by
      co-stimulation with type II collagen and TGF-beta1. Synergistically increased
      expression and nuclear translocation of pSMAD 2 and pSMAD 3 and GAG secretion of
      SW1353 cells were significantly inhibited by siFAK transfection. Therefore, we
      suggest that FAK-SMAD 2/3 mediates signal crosstalk between type II collagen and
      TGF-beta1 and regulates GAG secretion in chondrocytic cells.

PMID- 19840849
TI  - Extracellular matrix assembly and organization during zebrafish gastrulation.
AB  - Zebrafish gastrulation entails morphogenetic cell movements that shape the body
      plan and give rise to an embryo with defined anterior-posterior and dorsal
      ventral axes. Regulating these cell movements are diverse signaling pathways and
      proteins including Wnts, Src-family tyrosine kinases, cadherins, and matrix
      metalloproteinases. While our knowledge of how these proteins impact cell
      polarity and migration has advanced considerably in the last decade, almost no
      data exist regarding the organization of extracellular matrix (ECM) during
      zebrafish gastrulation. Here, we describe for the first time the assembly of a
      fibronectin (FN) and laminin containing ECM in the early zebrafish embryo. This
      matrix was first detected at early gastrulation (65% epiboly) in the form of
      punctae that localize to tissue boundaries separating germ layers from each other
      and the underlying yolk cell. Fibrillogenesis increased after mid-gastrulation
      (80% epiboly) coinciding with the period of planar cell polarity pathway
      dependent convergence and extension cell movements. We demonstrate that FN
      fibrils present beneath deep mesodermal cells are aligned in the direction of
      membrane protrusion formation. Utilizing antisense morpholino oligonucleotides,
      we further show that knockdown of FN expression causes a convergence and
      extension defect. Taken together, our data show that similar to amphibian
      embryos, the formation of ECM in the zebrafish gastrula is a dynamic process that
      occurs in parallel to at least a portion of the polarized cell behaviors shaping
      the embryonic body plan. These results provide a framework for uncovering the
      interrelationship between ECM structure and cellular processes regulating
      convergence and extension such as directed migration and mediolateral/radial
      intercalation.

PMID- 19840850
TI  - Purification, characterization and sequencing of the major beta-1,3-glucanase
      from the midgut of Tenebrio molitor larvae.
AB  - The major beta-1,3-glucanase from Tenebrio molitor (TLam) was purified to
      homogeneity (yield, 6%; enrichment, 113 fold; specific activity, 4.4 U/mg). TLam
      has a molecular weight of 50 kDa and a pH optimum of 6. It is an endoglucanase
      that hydrolyzes beta-1,3-glucans as laminarin and yeast beta-1,3-1,6-glucan, but
      is inactive toward other polysaccharides (as unbranched beta-1,3-glucans or mixed
      beta-1,3-1,4-glucan from cereals) or disaccharides. The enzyme is not inhibited
      by high substrate concentrations and has low processivity (0.6). TLam has two
      ionizable groups involved in catalysis, and His, Tyr and Arg residues plus a
      divalent ion at the active site. A Cys residue important for TLam activity is
      exposed after laminarin binding. The cDNA coding for this enzyme was cloned and
      sequenced. It belongs to glycoside hydrolase family 16, and is related to other
      insect glucanases and glucan-binding proteins. Sequence analysis and homology
      modeling allowed the identification of some residues (E174, E179, H204, Y304,
      R127 and R181) at the active site of the enzyme, which may be important for TLam
      activity. TLam efficiently lyses fungal cells, suggesting a role in making
      available walls and cell contents to digestion and in protecting the midgut from
      pathogen infections.

PMID- 19840851
TI  - Antigen-specific recognition is critical for the function of regulatory
      CD8(+)CD28(-) T cells.
AB  - The immunomodulatory properties of CD8 T cells with regulatory phenotype have
      become evident. It remains unclear whether the immunomodulatory function of
      CD8(+)CD28(-) T cells requires antigen-specific TCR interaction with major
      histocompatibility complex class I (MHC I). We have isolated naive CD8(+)CD28(-)
      T suppressor cells (Tsup) from H2-Kk Des-TCR mice that express a transgenic, MHC
      class I-restricted, clonotypic TCR against an allogeneic MHC class I molecule (H2
      Kb) plus self-peptide. These cells were compared to B10.BR wild type (w/t)
      CD8(+)CD28(-) T cells and to naive CD4(+)CD25(+) regulatory T cells (Treg) of the
      same strains. Des CD8 effector T cells proliferated more readily when stimulated
      by H2-Kb splenocytes than w/t controls, whereas Des CD4 T cells showed the same
      alloresponse as w/t cells. Activation and proliferation of B10.BR CD4 T cells
      stimulated by H2-Kb APC were suppressed more effectively by Des CD8(+)CD28(-) T
      cells than by w/t CD8(+)CD28(-) T cells. On the contrary, Des CD4(+)CD25(+) T
      cells inhibited T cell proliferation less effectively than w/t CD4(+)CD25(+) T
      cells. In conclusion, we demonstrate that the function of naive Tsup is strongly
      enhanced by antigen recognition. Therefore we expect that Tsup are possible
      candidates for antigen-specific immunosuppressive therapy.

PMID- 19840854
TI  - Tumour necrosis factor-alpha impairs neuronal differentiation but not
      proliferation of hippocampal neural precursor cells: Role of Hes1.
AB  - Tumour necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine, which
      influences neuronal survival and function yet there is limited information
      available on its effects on hippocampal neural precursor cells (NPCs). We show
      that TNFalpha treatment during proliferation had no effect on the percentage of
      proliferating cells prepared from embryonic rat hippocampal neurosphere cultures,
      nor did it affect cell fate towards either an astrocytic or neuronal lineage when
      cells were then allowed to differentiate. However, when cells were differentiated
      in the presence of TNFalpha, significantly reduced percentages of newly born and
      post-mitotic neurons, significantly increased percentages of astrocytes and
      increased expression of TNFalpha receptors, TNF-R1 and TNF-R2, as well as
      expression of the anti-neurogenic Hes1 gene, were observed. These data indicate
      that exposure of hippocampal NPCs to TNFalpha when they are undergoing
      differentiation but not proliferation has a detrimental effect on their neuronal
      lineage fate, which may be mediated through increased expression of Hes1.

PMID- 19840852
TI  - D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in
      a model of ADHD.
AB  - Low doses of psychostimulants produce beneficial behavioral effects in ADHD
      patients but the mechanisms underlying the response are not understood. Here we
      use the hyperactive mouse mutant coloboma to identify D2-like dopamine receptor
      subtypes that mediate the hyperactivity and response to amphetamine; we have
      previously demonstrated that D1-like dopamine receptors are not involved.
      Targeted deletion of the D2, but not the D3 or the D4, dopamine receptor in
      coloboma mice eliminated the hyperactivity; depleting D2 dopamine receptors also
      restored the excess dopamine overflow that may drive the hyperactivity to normal
      concentrations. Similar to its effects on ADHD patients, amphetamine reduced the
      hyperactivity of coloboma mice. The D2 dopamine receptor-selective antagonist L
      741,626, but not D3 or D4 dopamine receptor-selective antagonists, blocked the
      amphetamine-induced reduction in locomotor activity. Thus, the D2 dopamine
      receptor subtype mediates both the hyperactivity and response to amphetamine,
      suggesting a specific target for novel therapeutics in ADHD.

PMID- 19840855
TI  - Efficient refolding of recombinant lipase from Escherichia coli inclusion bodies
      by response surface methodology.
AB  - An experimental design was employed to optimize the refolding conditions of a
      recombinant lipase from Pseudomonas sp. which expressed as inclusion bodies in
      Escherichia coli. The effects of several variables on the refolding and
      activation of the enzyme has been studied. Because of the complexity of the
      reaction with respect to the number of parameters that can affect the refolding
      efficiency, 2(6-1) half-fractional factorial design (H-FFD) was employed for
      initial screening of the factors, potentially influencing the response.
      Experiments were performed in triplicate at two levels. Subsequently, the
      selected factors were subjected to response surface methodology (RSM) with a four
      factor-five coded level central composite design (CCD), using Quadratic model for
      obtaining the optimum values for the factors. The adequacy of the calculated
      model was confirmed by the coefficient of determination (R(2)) and F value of
      0.89 and 9.12, respectively. The optimized condition for the refolding was
      obtained in the refolding buffer containing unfolded lipase (10 microg/ml) and
      foldase (3 microg/ml) in combination with glycerol (10%), NaCl (1M) and sucrose
      (0.5M). Using chemicals in combination with foldase under the optimal condition
      exhibited a 50% increase in refolding yield over the conventional method.

PMID- 19840856
TI  - A single WAP domain (SWD)-containing protein with antipathogenic relevance in red
      swamp crayfish, Procambarus clarkii.
AB  - Single WAP domain-containing proteins (SWDs) are small proteins possessing a whey
      acidic protein (WAP) domain at the C-terminal region. In this study, a
      complementary deoxyribonucleic acid (cDNA) of SWD-containing protein was isolated
      from the hemocytes of red swamp crayfish, Procambarus clarkii called Pc-SWD. The
      full-length cDNA sequence is 998 bp. The deduced amino acid sequence consists of
      74 residues with a signal peptide of 20 residues. The mature peptide has a single
      WAP domain which contains eight conserved cysteine residues forming a "four
      disulphide core" (4-DSC). The predicted molecular mass of the mature protein is
      5.97 kDa, with an estimated pI of 7.71. Tissue distribution analysis by reverse
      transcribed polymerase chain reaction (RT-PCR) revealed that Pc-SWD transcripts
      were primarily found in the hemocytes, heart, hepatopancreas, gills, and
      intestine. The results of time course analysis demonstrated that expression of Pc
      SWD was decreased at 6 h followed by a significant upregulation from 48 h to 72 h
      in hemocytes after white spot syndrome virus (WSSV) injection. A similar
      expression pattern was found in the hepatopancreas after WSSV injection. In
      addition, Pc-SWD expression was visibly upregulated in the gills from 6 h to 72 h
      after WSSV injection. The results of Western bolt revealed that Pc-SWD was
      constitutively expressed in the heart, hepatopancreas, gills, and intestine of
      unchallenged crayfish. A weak band was detected in the hemocytes and hemolymph of
      unchallenged P. clarkii. The Pc-SWD expression was upregulated in the hemocytes
      and gills after challenging with WSSV; however, no obvious change occurred in the
      heart and intestine. rPc-SWD could bind to both Gram-negative and -positive
      bacteria strongly. Moreover, rPc-SWD exhibited specific proteinase inhibitory
      activity against the secretory proteinase(s) from B. subtilis and P. aeruginosa.
      All these findings suggest that Pc-SWD possibly functions as an immunity effector
      in defense against the invasion of crayfish pathogens.

PMID- 19840853
TI  - Viral vectors for neurotrophic factor delivery: a gene therapy approach for
      neurodegenerative diseases of the CNS.
AB  - The clinical manifestation of most diseases of the central nervous system results
      from neuronal dysfunction or loss. Diseases such as stroke, epilepsy and
      neurodegeneration (e.g. Alzheimer's disease and Parkinson's disease) share common
      cellular and molecular mechanisms (e.g. oxidative stress, endoplasmic reticulum
      stress, mitochondrial dysfunction) that contribute to the loss of neuronal
      function. Neurotrophic factors (NTFs) are secreted proteins that regulate
      multiple aspects of neuronal development including neuronal maintenance,
      survival, axonal growth and synaptic plasticity. These properties of NTFs make
      them likely candidates for preventing neurodegeneration and promoting
      neuroregeneration. One approach to delivering NTFs to diseased cells is through
      viral vector-mediated gene delivery. Viral vectors are now routinely used as
      tools for studying gene function as well as developing gene-based therapies for a
      variety of diseases. Currently, many clinical trials using viral vectors in the
      nervous system are underway or completed, and seven of these trials involve NTFs
      for neurodegeneration. In this review, we discuss viral vector-mediated gene
      transfer of NTFs to treat neurodegenerative diseases of the central nervous
      system.

PMID- 19840857
TI  - Oscillatory activity in prefrontal and posterior regions during implicit letter
      location binding.
AB  - Many cognitive abilities involve the integration of information from different
      modalities, a process referred to as "binding." It remains less clear, however,
      whether the creation of bound representations occurs in an involuntary manner,
      and whether the links between the constituent features of an object are
      symmetrical. We used magnetoencephalography to investigate whether oscillatory
      brain activity related to binding processes would be observed in conditions in
      which participants maintain one feature only (involuntary binding); and whether
      this activity varies as a function of the feature attended to by participants
      (binding asymmetry). Participants performed two probe recognition tasks that were
      identical in terms of their perceptual characteristics and only differed with
      respect to the instructions given (to memorize either consonants or locations).
      MEG data were reconstructed using a current source distribution estimation in the
      classical frequency bands. We observed implicit verbal-spatial binding only when
      participants successfully maintained the identity of consonants, which was
      associated with a selective increase in oscillatory activity over prefrontal
      regions in all frequency bands during the first half of the retention period and
      accompanied by increased activity in posterior brain regions. The increase in
      oscillatory activity in prefrontal areas was only observed during the verbal
      task, which suggests that this activity might be signaling neural processes
      specifically involved in cross-code binding. Current results are in agreement
      with proposals suggesting that the prefrontal cortex function as a "pointer"
      which indexes the features that belong together within an object.

PMID- 19840858
TI  - Hidden Mediterranean diversity: assessing species taxa by molecular phylogeny
      within the opilionid family Trogulidae (Arachnida, Opiliones).
AB  - This is the first comprehensive study to evaluate the relationships between the
      western palearctic harvestman families Dicranolasmatidae, Trogulidae and
      Nemastomatidae with focus on the phylogeny and systematics of Trogulidae, using
      combined sequence data of the nuclear 28S rRNA and the mitochondrial cytochrome b
      gene. Bayesian analysis and Maximum parsimony do not reliably resolve
      Dicranolasma as distinct family but place it on a similar phylogenetic level as
      several lineages of Trogulidae. Nemastomatidae and Trogulidae turned out to be
      monophyletic, as did genera Anelasmocephalus and Trogulus within the Trogulidae.
      The genera Calathocratus, Platybessobius and Trogulocratus each appeared para or
      polyphyletic, respectively and are synonymized with Calathocratus. The monotypic
      genus Kofiniotis is well supported. We show molecular data to be in general
      concordance with taxa characterized by morphology. Molecular data are especially
      useful to calibrate morphological characters for systematic purposes within
      homogeneous taxa. In the majority of closely related valid species we show the
      lowest level of genetic distance to be not lower than 5%. By this threshold in
      terms of traditionally accepted species the estimated number of species turns out
      to be 1.5-2.4 times higher than previously believed. With respect to European
      fauna cryptic diversity in Trogulidae is obviously extraordinarily high and
      hitherto largely underestimated.

PMID- 19840859
TI  - Sequence analysis of a bacteriocinogenic plasmid of Clostridium butyricum and
      expression of the bacteriocin gene in Escherichia coli.
AB  - A small cryptic plasmid, namely, pCBM588, was obtained from Clostridium butyricum
      MIYAIRI 588 (CBM588)--a bacterium used in probiotics. The complete sequence of
      pCBM588 was determined. The size of pCBM588 was 8060 bp and the G + C content was
      24.3%. Nine open reading frames (ORFs) were predicted, and ORF3 showed
      significant homologies with a structural bacteriocin gene of Clostridium
      tyrobutyricum. The putative bacteriocin gene was inserted into the pET21d
      expression vector in frame; it was expressed as a His-tagged recombinant protein
      in Escherichia coli BL21 (DE3). A total of 10240AU of the recombinant bacteriocin
      were purified from 100 ml of E. coli culture. The bacteriocin was cleaved into 2
      portions, and the small C-terminal polypeptide consisting of 83 amino acids
      possessed bactericidal activity. These results demonstrated that the ORF3 of
      pCBM588 encoded a bacteriocin, which is identical or very similar to the
      previously reported butyricin 7423.

PMID- 19840860
TI  - Molecular biology of cancer-associated fibroblasts: can these cells be targeted
      in anti-cancer therapy?
AB  - It is increasingly recognized that the non-neoplastic stromal compartment in most
      solid cancers plays an active role in tumor proliferation, invasion and
      metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant
      cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence
      that CAFs are epigenetically and possibly also genetically distinct from normal
      fibroblasts is beginning to define these cells as potential targets of anti
      cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs,
      arguing that such knowledge provides a rational basis for designing therapeutic
      strategies to coordinately and synergistically target both the stromal and
      malignant epithelial component of human cancers.

PMID- 19840861
TI  - A comparative analysis of parvalbumin expression in pinfish (Lagodon rhomboides)
      and toadfish (Opsanus sp.).
AB  - This study examines the role of a myoplasmic protein, parvalbumin, in enhancing
      muscle relaxation by fishes. Parvalbumin is thought to bind free Ca(2+) during
      muscle contraction, thereby reducing intracellular [Ca(2+)] in muscle and
      speeding muscle relaxation by reducing Ca(2+) availability to the troponin
      complex. We hypothesized that parvalbumin expression is ubiquitously expressed in
      fish muscle and that its expression levels and role in muscle relaxation would
      depend on the activity level and the thermal environment of a given fish species.
      Muscle contractile properties and patterns of parvalbumin expression were
      examined in pinfish (Lagodon rhomboides) and two species of toadfish (gulf
      toadfish, Opsanus beta, and oyster toadfish, Opsanus tau). Unlike another sparid
      (sheepshead), the active swimming pinfish does not express parvalbumin in its
      slow-twitch red muscle. However, both sheepshead and pinfish have relatively high
      levels of parvalbumin in their myotomal white muscle. Gulf toadfish from the Gulf
      of Mexico expressed higher levels of parvalbumin and had faster muscle relaxation
      rates than oyster toadfish from more northern latitudes. The faster muscle of
      gulf toadfish also expressed relatively more of one parvalbumin isoform,
      suggesting differences in the binding properties of the two isoforms observed in
      toadfish swimming muscle. Parvalbumin expression and its role in muscle
      relaxation appear to vary widely in fishes. There are many control points
      involved in the calcium transient of contracting muscle, leading to a variety of
      species-specific solutions to the modulation of muscle relaxation.

PMID- 19840862
TI  - Model-driven evaluation of the production potential for growth-coupled products
      of Escherichia coli.
AB  - Integrated approaches utilizing in silico analyses will be necessary to
      successfully advance the field of metabolic engineering. Here, we present an
      integrated approach through a systematic model-driven evaluation of the
      production potential for the bacterial production organism Escherichia coli to
      produce multiple native products from different representative feedstocks through
      coupling metabolite production to growth rate. Designs were examined for 11
      unique central metabolism and amino acid targets from three different substrates
      under aerobic and anaerobic conditions. Optimal strain designs were reported for
      designs which possess maximum yield, substrate-specific productivity, and
      strength of growth-coupling for up to 10 reaction eliminations (knockouts). In
      total, growth-coupled designs could be identified for 36 out of the total 54
      conditions tested, corresponding to eight out of the 11 targets. There were 17
      different substrate/target pairs for which over 80% of the theoretical maximum
      potential could be achieved. The developed method introduces a new concept of
      objective function tilting for strain design. This study provides specific
      metabolic interventions (strain designs) for production strains that can be
      experimentally implemented, characterizes the potential for E. coli to produce
      native compounds, and outlines a strain design pipeline that can be utilized to
      design production strains for additional organisms.

PMID- 19840863
TI  - The role of HIF in immunity.
AB  - Oxygen is an essential nutrient for eukaryotic life and in complex organisms a
      finely tuned system, based on Hypoxia Inducible Factor (HIF), has evolved to
      control the cellular, local and organism-wide responses to its availability.
      Cells of the immune system must function in a variety of local environments and
      it is now clear that oxygen availability is an important signal for the cells
      involved in immune defence. This review summarises the mechanisms by which
      activation of the HIF pathway influences, and is influenced by, both immune
      activation state and oxygen tension. It is likely that understanding how oxygen
      tension modulates immune function will provide insights into disease
      pathogenesis, and may offer new opportunities for treatment.

PMID- 19840864
TI  - TLRs and chronic inflammation.
AB  - After the discovery of Toll-like receptors (TLRs), innate immune mechanisms came
      back in the focus of scientific research. With more and more mechanisms of TLR
      biology known, it has become clear that these and also other innate immune
      receptors are not only of crucial importance in the immune response to invading
      pathogens, but also play a role in the homeostasis of commensal flora and in the
      response to stress and danger signals. In this respect, increasing evidence is
      found that inappropriate quantity or quality of TLR ligands or aberrant response
      to TLR activation plays a role in a variety of chronic inflammatory diseases. In
      this review, an overview of the currently known TLRs and their signaling pathways
      is given and reports about their expression and activation in chronic
      inflammatory diseases are recapitulated.

PMID- 19840865
TI  - Oxytocin in health and disease.
AB  - Oxytocin is a nonapeptide of the neurohypophyseal protein family that binds
      specifically to the oxytocin receptor to produce a multitude of central and
      peripheral physiological responses. Within the central nervous system oxytocin is
      expressed by the neurons of the hypothalamus that project into higher brain
      centres and the posterior pituitary gland, from where it enters the circulation
      by release into the portal capillaries. Centrally, it modulates, maternal,
      sexual, social and stress related behaviour. Peripheral actions of oxytocin are
      commonly associated with smooth muscle contraction, particularly within the
      female and male reproductive tracts. Local synthesis of oxytocin along with its
      receptor in these regions indicates the presence of local oxytocinergic systems.
      More sinister implications for oxytocin in autism, depression and several cancers
      have recently been identified. A greater understanding of the role of
      oxytocinergic mechanisms will determine the potential for targeting this
      regulatory peptide in the pharmacological management of these disorders.

PMID- 19840866
TI  - Visualizing the drug target landscape.
AB  - Generating new therapeutic hypotheses for human disease requires the analysis and
      interpretation of many different experimental datasets. Assembling a holistic
      picture of the current landscape of drug discovery activity remains a challenge,
      however, because of the lack of integration between biological, chemical and
      clinical resources. Although tools designed to tackle the interpretation of
      individual data types are abundant, systems that bring together multiple elements
      to directly enable decision making within drug discovery programmes are rare. In
      this article, we review the path that led to the development of a knowledge
      system to tackle this problem within our organization and highlight the
      influences of existing technologies on its development. Central to our approach
      is the use of visualization to better convey the overall meaning of an integrated
      set of data including disease association, druggability, competitor intelligence,
      genomics and text mining. Organizing such data along lines of therapeutic
      precedence creates clearly distinct 'zones' of pharmaceutical opportunity,
      ranging from small-molecule repurposing to biotherapeutic prospects and gene
      family exploitation. Mapping content in this way also provides a visual alerting
      mechanism that evaluates new evidence in the context of old, reducing information
      overload by filtering redundant information. In addition, we argue the need for
      more tools in this space and highlight the role that data standards, new
      technologies and increased collaboration might have in achieving this aim.

PMID- 19840867
TI  - A novel form of Total Internal Reflection Fluorescence Microscopy (LG-TIRFM)
      reveals different and independent lipid raft domains in living cells.
AB  - In the present study we have applied a novel form of Total Internal Reflection
      Fluorescence Microscopy (LG-TIRFM) in combination with fluorescently labeled
      cholera toxin to the study of lipid rafts dynamics in living cells. We
      demonstrate the usefulness of such approach by showing the dynamic
      formation/disaggregation of islands of cholera toxin on the surface of cells.
      Using multicolor LG-TIRFM with co-localization studies we show for the first time
      that two receptors previously identified as constituents of lipid rafts are found
      on different and independent "raft domains" on the cell plasma membrane.
      Furthermore, LG-TIRFM studies revealed limited association and dissociation of
      both domains overtime on different areas of the plasma membrane. The implications
      of different "raft domains" on cell physiology are discussed.

PMID- 19840868
TI  - Exposure of the blue mussel, Mytilus edulis, to gold nanoparticles and the pro
      oxidant menadione.
AB  - Relatively little is known about how gold nanoparticles (GNP) might interact in
      vivo with marine organisms. Mytilus edulis was exposed (24h) to approximately 15
      nm GNP, menadione and both compounds simultaneously (GNP/menadione). GNP was
      detected by inductively coupled plasma-optical emission spectroscopy mainly in
      digestive gland of samples exposed to GNP though not GNP/menadione, perhaps due
      to impaired feeding. Thioredoxin reductase activity and malondialdehyde levels
      were determined in all tissues. Thioredoxin reductase inhibition was detected
      only in digestive gland exposed to menadione whilst malondialdehyde levels did
      not vary in response to treatment in all tissues. GNP caused a decrease in the
      reduced/oxidized glutathione ratio in digestive gland, but no difference was
      found in other tissues or for other treatments. One dimensional electrophoresis
      of proteins containing thiol groups was performed in all tissues and revealed a
      reduction in protein thiols for all treatments in digestive gland. Two
      dimensional electrophoresis of digestive gland extracts, from GNP and control
      groups, showed decreased levels of thiol proteins in response to GNP which we
      attribute to oxidation. Our results suggest that GNP causes a modest level of
      oxidative stress sufficient to oxidize thiols in glutathione and proteins but
      without causing lipid peroxidation or induction of thioredoxin reductase
      activity.

PMID- 19840869
TI  - Induced keratinocyte hyper-proliferation in alpha2beta1 integrin transgenic mice
      results in systemic immune cell activation.
AB  - alpha2beta1 integrins are normally confined to the proliferating basal layers of
      the epidermis. However, during wound healing and in psoriasis, these integrins
      are expressed on keratinocytes in suprabasal layers correlating with a less
      differentiated phenotype. Transgenic mice expressing alpha2beta1 integrins under
      the involucrine promoter have previously been demonstrated, to various degrees,
      spontaneously develop a skin disorder resembling psoriasis. Herein, we show that
      a mild epidermal wounding induces a uniform acanthosis together with an influx of
      immune cells. The disease initiates as a normal wound healing process and is
      completely restored in wildtype mice by day 14. However, in the integrin
      transgenic mice a chronic inflammation develops, a process that can be compared
      to the Koebner phenomenon in psoriatic patients. In this study, we have followed
      the integrin transgenic mice for five weeks, where substantial keratinocyte hyper
      proliferation, inflammatory infiltration and high cytokine levels within the skin
      can still be observed. In addition, draining lymph nodes were dramatically
      increased in size and contained highly activated T cells, as well as APCs
      secreting large amounts of pro-inflammatory cytokines. Furthermore, the systemic
      immune response was affected with increased spleen size, elevated cytokine levels
      in the serum and altered lymphocyte trafficking patterns, very much resembling
      what is seen in psoriasis patients. Finally, CD4(+) T cell depletion was not able
      to affect the onset or progression of skin inflammation. This suggests that
      altered keratinocyte differentiation and proliferation can drive a skin
      inflammation and cause chronic immune cell activation both at a local and
      systemic level.

PMID- 19840870
TI  - Is neuroimmunomodulation a future therapeutic approach for sepsis?
AB  - Sepsis is considered as a disease of profoundly and uncontrollably activated
      innate immune response against bacterial infection or their products. Thus,
      regulation of innate immune response plays a critical role in controlling
      exaggerated systemic inflammation responsible for sepsis development. However,
      treatment of patients suffering from sepsis or its more severe form (i.e. severe
      sepsis or septic shock) with available antibiotics or immunomodulatory agents did
      not prove effective in controlling multi organ damage and mortality. Therefore it
      is important to explore cascades of mechanisms associated with pathogenesis of
      sepsis causing high mortality. The nervous system via peripheral nervous system
      (PNS) or sympathetic nervous system (SNS) along with hypothalamic pituitary axis
      (HPA) regulates the innate immune response. Thus the nervous system may play an
      important role in fine tuning and precise regulation of exaggerated innate immune
      response via different pathways (i.e. cholinergic pathway activated by vagus
      nerve stimulation, alpha- or beta-adrenergic receptor activation etc.) in sepsis.
      Hence neuroimmunomodulation can be a future approach to treat sepsis.

PMID- 19840871
TI  - CD14 but not MD2 transmit signals from DAMP.
AB  - Both pathogen-associated molecular patterns (PAMPs) and damage-associated
      molecular patterns (DAMPs) activate antigen-presenting cells, often through the
      same pattern recognition receptors (PRR), such as Toll-like receptors (TLR). The
      TLR4-CD14-MD2 and TLR2-CD14 complexes have been shown to play a role in the
      recognition of lipopolysaccharide (LPS) and peptidoglycan (PG), respectively.
      Since many DAMPs have also been known to activate TLR2 or TLR4 pathways, we
      dissected the role of each molecule in the receptor complexes (TLR2-D14-MD2)
      responding to DAMP (necrotic cells) or PAMP (LPS and PG). CD14 played a
      significant role in the activation of NF-kappaB in response to necrotic cells in
      the presence or absence of TLR2. However, MD2 did not play a significant role in
      NF-kappaB activation by necrotic cells. Intriguingly, MD2 did play a significant
      role in activating NF-kappaB by PG in the presence of TLR2-CD14. Compared with
      CD14(pos) B6 mice, CD14(neg) B6 mice showed delayed production of IL12p40 in
      response to necrotic cells in vivo. Microarray analysis showed that various pro
      inflammatory genes of peritoneal cells were regulated in response to necrotic
      cells, in a CD14-dependent manner. The CD14 appears to recognize necrotic cells
      in addition to LPS, PG, apoptotic cells, and lipids, suggesting that CD14 might
      be a universal adaptor for DAMP and PAMP. On the contrary, MD2 recognizes only
      exogenous PAMP, when complexed with TLR2-CD14 or TLR4-CD14. Taken together, MD2
      appears to discriminate between DAMP and PAMP.

PMID- 19840872
TI  - Effect of the inosine 5'-monophosphate dehydrogenase inhibitor BMS-566419 on rat
      cardiac allograft rejection.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) inhibition is a critical target in
      solid organ transplantation, and the development of mycophenolate mofetil (MMF)
      represents a major advance in transplant medicine. In this study, the in vitro
      and in vivo pharmacological effects of BMS-566419, a novel chemically synthesized
      IMPDH inhibitor, were compared to those of mycophenolic acid (MPA) and MMF based
      on results from several immunological experiments. The in vitro inhibitory
      activity of BMS-566419 on IMPDH type I/II, immune cell proliferation and antibody
      production from lipopolysaccharide (LPS)-stimulated B cells was similar, albeit
      slightly less potent than that of MPA. In a rat heterotopic cardiac transplant
      model, monotherapy using orally administered BMS-566419 60mg/kg or MMF 40mg/kg
      prolonged the median survival time (MST) of transplanted grafts in the vehicle
      group from 5 to 18 and 18.5 days, respectively. In the presence of a sub
      therapeutic dose of FK506, BMS-566419 30mg/kg and MMF 20mg/kg showed identical
      efficacy with an MST of 21.5 days. In dinitrophenol-LPS-stimulated rats in which
      calcineurin inhibitors failed to inhibit antibody production, in vivo oral
      administration of BMS-566419 resulted in antibody production suppression with
      similar efficacy to MMF. The in vivo antibody production against alloantigen was
      also suppressed by MMF or BMS-566419 treatment. In addition, gastrointestinal
      toxicity, considered a dose-limiting factor of MMF, was reduced in BMS-566419
      treatment. These results suggest that BMS-566419 and other chemically synthesized
      IMPDH inhibitors have beneficial pharmacological effects similar to those of MMF,
      and are potential pharmaceutical candidates in transplant indications.

PMID- 19840873
TI  - Antibody concentrations to Abeta1-42 monomer and soluble oligomers in untreated
      and antibody-antigen-dissociated intravenous immunoglobulin preparations.
AB  - Cognitive improvement in Alzheimer's disease (AD) patients treated with
      intravenous immunoglobulin (IvIg) has been attributed to its antibodies to
      amyloid beta (Abeta). We compared the concentrations of specific antibodies to
      soluble Abeta1-42 conformations, namely Abeta1-42 monomer and Abeta1-42 soluble
      oligomers, between three IvIg preparations, Gamunex, Gammagard, and Flebogamma.
      To determine specific antibody concentrations to these Abeta1-42 conformations,
      nonspecific binding of the IvIg preparations to the Abeta reverse sequence,
      Abeta42-1, was subtracted. These antibodies were measured in untreated IvIg
      preparations and also after they were treated to dissociate antibody-antigen
      complexes, because this procedure has been reported to increase the detectable
      levels of serum anti-Abeta antibodies. Antibody levels to Abeta1-42 monomer were
      significantly higher in untreated Gamunex than in the other two IvIg
      preparations, and antibody-antigen dissociation increased the measured anti-Abeta
      monomer concentrations in Gamunex and Gammagard. Dissociated Gamunex and
      Gammagard had higher anti-Abeta monomer levels than Flebogamma. Generally similar
      results were found for antibodies to soluble Abeta1-42 oligomers, with the
      exception that after antibody-antigen dissociation, only Gammagard had
      significantly higher antibody levels than Flebogamma. These differences in
      antibody concentrations to Abeta1-42 conformations (particularly to Abeta1-42
      soluble oligomers, thought to be the most neurotoxic conformation of soluble
      Abeta) and the increased availability of these antibodies after antibody-antigen
      complex dissociation have important implications for IvIg treatment of AD
      patients.

PMID- 19840874
TI  - Malaria: targeting parasite and host cell kinomes.
AB  - Malaria still remains one of the deadliest infectious diseases, and has a
      tremendous morbidity and mortality impact in the developing world. The propensity
      of the parasites to develop drug resistance, and the relative reluctance of the
      pharmaceutical industry to invest massively in the developments of drugs that
      would offer only limited marketing prospects, are major issues in antimalarial
      drug discovery. Protein kinases (PKs) have become a major family of targets for
      drug discovery research in a number of disease contexts, which has generated
      considerable resources such as kinase-directed libraries and high throughput
      kinase inhibition assays. The phylogenetic distance between malaria parasites and
      their human host translates into important divergences in their respective
      kinomes, and most Plasmodium kinases display atypical properties (as compared to
      mammalian PKs) that can be exploited towards selective inhibition. Here, we
      discuss the taxon-specific kinases possessed by malaria parasites, and give an
      overview of target PKs that have been validated by reverse genetics, either in
      the human malaria parasite Plasmodium falciparum or in the rodent model
      Plasmodium berghei. We also briefly allude to the possibility of attacking
      Plasmodium through the inhibition of human PKs that are required for survival of
      this obligatory intracellular parasite, and which are targets for other human
      diseases.

PMID- 19840875
TI  - Poly(ethylene glycol)-based magnetic hydrogel nanocomposites for hyperthermia
      cancer therapy.
AB  - Hyperthermia, the heating of cancerous tissues to between 41 and 45 degrees
      Celsius, has been shown to improve the efficacy of cancer therapy when used in
      conjunction with irradiation and/or chemotherapy. Here a novel method for
      remotely administering heat is presented, which involves the heating of tumor
      tissue using hydrogel nanocomposites containing magnetic nanoparticles which can
      be remotely heated upon exposure to an external alternating magnetic field (AMF).
      Specifically, this research explores the use of hydrogel nanocomposites based on
      poly(ethylene glycol) methyl ether methacrylate and dimethacrylate with iron
      oxide as implantable biomaterials for thermal cancer therapy applications.
      Swelling analysis of the systems indicated a dependence of ethylene glycol (EG)
      content and cross-linking density on swelling behavior where greater EG amount
      and lower cross-linking resulted in higher volume swelling ratios. Both the
      entrapped iron oxide nanoparticles and hydrogel nanocomposites exhibited high
      cell viability for murine fibroblasts, indicating potential biocompatibility. The
      hydrogels were heated in an AMF, and the heating response was shown to be
      dependent on both iron oxide loading in the gels and the strength of the magnetic
      field. As proof of concept of these systems as a thermal therapeutic the ability
      to selectively kill M059K glioblastoma cells in vitro with hydrogel
      nanocomposites exposed to an AMF was demonstrated.

PMID- 19840876
TI  - Maximizing bone mineral mass gain during growth for the prevention of fractures
      in the adolescents and the elderly.
AB  - Bone mass is a key determinant of fracture risk. Maximizing bone mineral mass
      during childhood and adolescence may contribute to fracture risk reduction during
      adolescence and possibly in the elderly. Although more than 60% of the variance
      of peak bone mass (PBM), the amount of bone present in the skeleton at the end of
      its maturation process, is genetically determined, the remainder is likely
      influenced by factors amenable to positive intervention, such as adequate dietary
      intake of dairy products as a natural source of calcium and proteins, vitamin D,
      and regular weight-bearing physical activity. Low calcium and vitamin D intakes
      are associated with negative effects on bone, including suboptimal PBM
      acquisition. As suggested by intervention studies, regular intake of dairy
      products may have positive and possibly sustained effects on bone mineral mass
      gain, contributing thereby to fracture risk reduction. Further evidence from
      intervention studies suggests that weight-bearing physical activities, such as
      jumping, may contribute to bone mineral mass gain in children. Optimizing PBM
      acquisition through dietary and physical exercise measures may represent a
      valuable primary method for the prevention of fractures.

PMID- 19840877
TI  - Osmolarity effects on bovine articular chondrocytes during three-dimensional
      culture in alginate beads.
AB  - OBJECTIVE: With the development of engineered cartilage, the determination of the
      appropriate culture conditions is vital in order to maximize extracellular matrix
      synthesis. As osmolarity could affect the fate of chondrocytes, the purpose of
      this study was to determine the effects of osmolarity on chondrocytes during
      relatively long-term culture. DESIGN: Bovine articular chondrocytes were cultured
      in alginate beads in a biocarbonate free system at 280, 380 and 550 mOsm at pH
      7.4 for up to 12 days, respectively. Cell volume, intracellular pH (pH(i)), cell
      number, glucosaminoglycan (GAG) and collagen retention were measured at day 5 and
      12. Cell viability and volume were monitored over the 12 days of culture.
      RESULTS: By day 5 and 12, compared to the cell volume at 380 mOsm, around 20%
      (P<0.01) swelling and 15% (P<0.05) shrinkage were observed when the cells were
      cultured at 280 and 550 mOsm. The pH(i) over the 12 days of culture varied with
      osmolarity of the culture medium. In comparison with fresh cells, pH(i) became
      slightly more acidic by 0.15 pH units at 280 mOsm at day 5. However, by day 12,
      an alkalization of pH(i), by 0.2 pH units, was noted. A higher proliferation rate
      was seen at 280 mOsm than at other osmolarities while less GAG was produced.
      CONCLUSIONS: Chronic exposure to anisotonic conditions results in cell swelling
      at 280 mOsm and shrinkage at 550 mOsm. The osmolarity of 280 mOsm appears to
      encourage proliferation of chondrocytes, but inhibits matrix production.

PMID- 19840878
TI  - [Traditional or systematic clinical guides?].

PMID- 19840880
TI  - Hysterosalpingo-contrast sonography for infertility investigation.

PMID- 19840879
TI  - Residential proximity to industrial facilities and risk of non-Hodgkin lymphoma.
AB  - Industrial pollution has been suspected as a cause of non-Hodgkin lymphoma (NHL),
      based on associations with chemical exposures in occupational studies. We
      conducted a case-control study of NHL in four SEER regions of the United States,
      in which residential locations of 864 cases and 684 controls during the 10 years
      before recruitment were used to characterize proximity to industrial facilities
      reporting chemical releases to the Environmental Protection Agency's Toxics
      Release Inventory (TRI). For each of 15 types of industry (by 2-digit SIC code),
      we evaluated the risk of NHL associated with having lived within 2 miles of a
      facility, the distance to the nearest facility (miles categories of < or =0.5,
      >0.5-1.0, >1.0-2.0, >2 [referent]), and the duration of residence within 2miles
      (years categories of 10, 1-9, 0 [referent]), using logistic regression. Increased
      risk of NHL was observed in relation to lumber and wood products facilities (SIC
      24) for the shortest distance of residential proximity (< or =0.5 mile: odds
      ratio [OR]=2.2, 95% confidence interval [CI]: 0.4-11.8) or the longest duration
      (10 years: OR=1.9, 95% CI: 0.8-4.8); the association with lumber facilities was
      more apparent for diffuse large B-cell lymphoma (lived within 2 miles: OR=1.7,
      95% CI: 1.0-3.0) than for follicular lymphoma (OR=1.1, 95% CI: 0.5-2.2). We also
      observed elevated ORs for the chemical (SIC 28, 10 years: OR=1.5, 95% CI: 1.1
      2.0), petroleum (SIC 29, 10 years: OR=1.9, 95% CI: 1.0-3.6), rubber/miscellaneous
      plastics products (SIC 30, < or =0.5mile: OR=2.7, 95% CI: 1.0-7.4), and primary
      metal (SIC 33, lived within 2miles: OR=1.3, 95% CI: 1.0-1.6) industries; however,
      patterns of risk were inconsistent between distance and duration metrics. This
      study does not provide strong evidence that living near manufacturing industries
      increases NHL risk. However, future studies designed to include greater numbers
      of persons living near specific types of industries, along with fate-transport
      modeling of chemical releases, would be informative.

PMID- 19840881
TI  - The need for muscle co-contraction prior to a landing.
AB  - In landings from a flight phase the mass centre of an athlete experiences rapid
      decelerations. This study investigated the extent to which co-contraction is
      beneficial or necessary in drop landings, using both experimental data and
      computer simulations. High speed video and force recordings were made of an elite
      martial artist performing drop landings onto a force plate from heights of 1.2,
      1.5 and 1.8m. Matching simulations of these landings were produced using a planar
      8-segment torque-driven subject-specific computer simulation model. It was found
      that there was substantial co-activation of joint flexor and extensor torques at
      touchdown in all three landings. Optimisations were carried out to determine
      whether landings could be effected without any co-contraction at touchdown. The
      model was not capable of landing from higher than 1.05m with no initial flexor or
      extensor activations. Due to the force-velocity properties of muscle, co
      contraction with net zero joint torque at touchdown leads to increased extensor
      torque and decreased flexor torque as joint flexion velocity increases. The same
      considerations apply in any activity where rapid changes in net joint torque are
      required, as for example in jumps from a running approach.

PMID- 19840882
TI  - Symptomatic Moyamoya disease: clinical features and outcome after indirect bypass
      surgery in four French adults.
AB  - BACKGROUND: There are a few reports of moyamoya disease (MMD) in the European
      Caucasian adult population. We present the clinical manifestations, the
      neuroradiological aspects, the treatment, and the outcome after surgical
      revascularization of four French patients with MMD. PATIENTS AND METHODS: We
      identified four adults (age >18 years; three women and one man) with MMD who
      underwent digital subtraction catheter angiography at our institution from 1997
      through 2006. The median age at symptom onset was 35 years (range, 22 to 41
      years). The initial clinical presentation was intracerebral hemorrhage in three
      patients and ischemic stroke in one patient. RESULTS: Three patients underwent
      bilateral surgical revascularization and one patient underwent unilateral
      surgical revascularization. All patients underwent the same surgical
      revascularization procedure (encephalo-duro-arterio-myo-synangiosis). The mean
      (+/-SD) period of follow-up after diagnosis of MMD was 6 years and 9 months (+/-3
      years and 5 months). No patient experienced any recurrent hemorrhagic or ischemic
      stroke. No perioperative stroke occurred. No patient was severely disabled or
      unable to walk. Three patients out of four were employed. CONCLUSION: Our data
      suggest safety and a potential benefit of surgical revascularization (indirect
      bypass surgery) in European adult patients with symptomatic MMD. Further long
      term prospective multicenter studies are needed. The establishment of a registry
      would be useful in order to accumulate data in large numbers of European patients
      with this uncommon disease.

PMID- 19840883
TI  - Executive dysfunction in vascular cognitive impairment in the consortium to
      investigate vascular impairment of cognition study.
AB  - BACKGROUND AND PURPOSE: The importance of executive dysfunction is increasingly
      recognized in the dementia syndrome. Although executive dysfunction has been
      associated with subcortical ischemic lesions, it may not be unique to VCI or to
      its clinical subtypes. METHODS: Secondary analysis of the CIVIC study, a multi
      centre memory clinic cohort study. An executive dysfunction index variable was
      created using 30 items from the clinical evaluation. RESULTS: Of 1347 patients,
      151 had a baseline diagnosis of no cognitive impairment (NCI), 463 had AD, 324
      had VCI, 97 had vascular cognitive impairment not dementia (VCI-ND) and 253 had
      non-vascular CIND. Those with VCI and AD had higher mean executive dysfunction
      index values than those with NCI (F=160.2, p<0.01). Within the VCI subtypes,
      people with VaD and mixed dementia had the highest mean executive dysfunction
      index values (F=92.5, p<0.01). Higher executive dysfunction index values were
      significantly correlated with lower MMSE scores (R=0.70, p<0.01), higher
      Functional Rating Scale scores (R=0.77, p<0.01) and higher Geriatric Depression
      Score values (R=0.11, p<0.01). Compared to those who had a lower burden of
      executive dysfunction, patients with more executive dysfunction (index values
      >=0.2) were more likely to be institutionalized (HR=5.2, p<0.01) or to die
      (HR=2.4, p<0.01) during the next 30 months. CONCLUSIONS: Executive dysfunction is
      common in both AD and VCI. It is associated with poor performance on other
      measures of cognition and function. The presence of executive dysfunction is
      associated with worse near-term outcomes.

PMID- 19840884
TI  - The evidence for altered RNA metabolism in amyotrophic lateral sclerosis (ALS).
AB  - In this review, the role of aberrant RNA metabolism in ALS is examined, including
      the evidence that a majority of the genetic mutations observed in familial ALS
      (including mutations in TDP-43, FUS/TLS, SOD1, angiogenin (ANG) and senataxin
      (SETX)) can impact directly on either gene transcription, pre-mRNA splicing,
      ribonucleoprotein complex formation, transport, RNA translation or degradation.
      The evidence that perturbed expression or function of RNA binding proteins is
      causally related to the selective suppression of the low molecular weight subunit
      protein (NFL) steady state mRNA levels in degenerating motor neurons in ALS is
      examined. The discovery that mtSOD1, TDP-43 and 14-3-3 proteins, all of which
      form cytosolic aggregates in ALS, can each modulate the stability of NFL mRNA,
      suggests that a fundamental alteration in the interaction of mRNA species with
      key trans-acting binding factors has occurred in ALS. These observations lead
      directly to the hypothesis that ALS can be viewed as a disorder of RNA
      metabolism, thus providing a novel pathway for the development of molecular
      pharmacotherapies.

PMID- 19840885
TI  - Emissions of maritime transport: a European reference system.
AB  - Emissions from ships have recently received more attention since they have become
      a significant concern for air quality in harbours and port cities. This paper
      presents the methodology for a comprehensive maritime transport database of
      activity data, specific energy consumption, emission factors, and total emissions
      that have been developed within the European EX-TREMIS project. The model is
      built upon 3 modules: the fleet module, the transport activity module, and the
      emission module. The fleet module defines the ship categories, the loading
      capacities, and the engine characteristics of the different vessels by using
      EUROSTAT data, Sea Web Lloyd's database, and international literature. The
      transport activity module transforms total cargo handled (mainly based on
      EUROSTAT data and CEMT statistics) into ship-equivalents. These ship-equivalents
      are further transformed into ship-hours. The emission module calculates energy
      uses and CO(2), NO(X), SO(2), CO, HC, CH(4), NMHC, PM emissions from the
      resulting maritime activities. We have used technology based emission factors to
      take into account the technological evolution of vessels. To illustrate this new
      methodology, we present some results (emissions, fuel consumption and emission
      factors) for different countries. The overall methodology as well as the results
      and the country specific energy consumption and emission factors per ship type
      and size class can be extracted from the EX-TREMIS website (www.ex-tremis.eu).
      Our results contribute to more accurate estimates of emissions and air quality
      assessments in coastal cities and ports.

PMID- 19840886
TI  - Clinical relevance of extent of extreme drug resistance in epithelial ovarian
      carcinoma.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical significance
      of the extent of extreme drug resistance (EDR) in in vitro drug resistance assays
      in advanced epithelial ovarian, fallopian, and primary peritoneal cancers.
      METHODS: A retrospective study was conducted using the database for in vitro drug
      resistance assay (EDR Assay, Oncotech, Inc.) results for advanced stage ovarian
      cancer samples obtained at primary surgery between 1995 and 2009. In vitro drug
      resistance assay results were evaluated for thirteen drugs according to the
      following two groups: platinum and taxane (primary treatment group) vs remaining
      agents (secondary treatment group). Dual-resistance was then defined as at least
      one EDR in the primary and secondary treatment groups. Chemotherapy response and
      survival outcome were correlated with assay results. RESULTS: There were 253
      cases identified. Dual-resistance (n=53, 20.9%) was not associated with
      chemotherapy response (p=0.62) or survival outcomes (PFS, p=0.52; OS, p=0.11).
      Only one (0.4%) case exhibited complete EDR to all tested drugs, and 74 (29.4%)
      cases showed no EDR. There was no statistical correlation between total number of
      drugs in the EDR range and chemotherapy response (p=0.55), progression-free
      survival (PFS) (p=0.18), and overall survival (OS) (p=0.87). Proportion of EDR,
      defined as the ratio of the number of EDR drugs divided by all drugs for an
      individual patient, was also not related to chemotherapy response (p=0.37), PFS
      (p=0.13), or OS (p=0.13). CONCLUSIONS: Presence of extreme drug resistance to
      multiple agents in the in vitro drug resistance assays was not associated with
      survival outcomes in advanced stage epithelial ovarian, fallopian, and primary
      peritoneal cancers.

PMID- 19840887
TI  - Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive
      endometrial carcinoma: a Gynecologic Oncology Group study.
AB  - PURPOSE: This study evaluated efficacy of single-agent trastuzumab against
      advanced or recurrent HER2-positive endometrial carcinoma (EC), and explored
      predictors for HER2 amplification. PATIENTS AND METHODS: Eligible patients had
      measurable stage III, IV, or recurrent EC. There was no limit on prior therapy
      although total prior doxorubicin dose was limited to 320 mg/m(2). Tumors were
      required to have HER2 overexpression (2+ or 3+ immunohistochemical staining) or
      HER2 amplification (FISH HER2/CEP 17 ratio >2.0). Trastuzumab was administered
      intravenously at a dose of 4 mg/kg in week 1, then 2 mg/kg weekly until disease
      progression. The primary endpoint was tumor response. RESULTS: Of the 286 tumors
      centrally screened by LabCorp, 33 (11.5%) were HER2-amplified. Three of 8 clear
      (38%) cell carcinomas and 7 of 25 serous carcinomas (28%) screened exhibited HER2
      amplification compared with 7% (2/29) of endometrioid adenocarcinomas. HER2
      overexpression was correlated with HER2 amplification (r=0.459; p<0.0001). Thirty
      four women were enrolled; 1 was excluded (refused treatment); and 18 had tumors
      with known HER2 amplification. No major tumor responses were observed. Twelve
      women experienced stable disease, 18 had increasing disease, and 3 were
      indeterminate for tumor response. Neither HER2 overexpression nor HER2
      amplification appeared to be associated with progression-free survival or overall
      survival. CONCLUSION: Trastuzumab as a single agent did not demonstrate activity
      against endometrial carcinomas with HER2 overexpression or HER2 amplification,
      although full planned accrual of women with HER2 amplified tumors was not
      achieved due to slow recruitment. Serous and clear cell endometrial carcinomas
      appear to be more likely to demonstrate HER2 amplification.

PMID- 19840888
TI  - Immune allergic response in Asperger syndrome.
AB  - Asperger's syndrome is a subgroup of autism characterized by social deficits
      without language delay, and high cognitive performance. The biological nature of
      autism is still unknown but there are controversial evidence associating an
      immune imbalance and autism. Clinical findings, including atopic family history,
      serum IgE levels as well as cutaneous tests showed that incidence of atopy was
      higher in the Asperger group compared to the healthy controls. These findings
      suggest that atopy is frequent in this subgroup of autism implying that allergic
      inflammation might be an important feature in Asperger syndrome.

PMID- 19840889
TI  - Effects of perhexiline on myocardial deformation in patients with ischaemic left
      ventricular dysfunction.
AB  - BACKGROUND: Perhexiline improves functional capacity in heart failure, but the
      mechanisms are undefined. We sought its effects on myocardial deformation in
      patients with viable myocardium. METHODS: Thirty-six medically-treated patients,
      stable at least 6 months post-infarction with LV dysfunction and myocardial
      viability shown by dobutamine echo (DbE) were randomised to receive perhexiline
      or matching placebo for 1 year. Cardiopulmonary exercise testing and DbE were
      performed at baseline and follow-up. Peak-systolic strain (S) and strain rate
      (SR) were measured offline in 111 dysfunctional segments in the placebo and 88 in
      the treatment group at rest, low-dose (LDD) and peak-dose dobutamine (PDD).
      RESULTS: The serum perhexiline level was 0.27+/-0.7 microg/l. There was no
      difference in the wall motion response to dobutamine at baseline and follow-up.
      Resting strain and SR were similar in the two groups at baseline and follow-up.
      However, SR at LDD and PDD increased in the placebo group and worsened during the
      same period in the perhexiline group. Patients on perhexiline and placebo had a
      similar rate-pressure product and exercise duration at baseline (7.9+/-2.7 vs
      8.7+/-3.3 min, p=NS) and follow-up (9.6+/-4.6 vs 10.1+/-3.03 min, p=NS).
      CONCLUSION: Perhexiline does not improve the deformation of abnormal myocardial
      segments in patients with ischaemic LV dysfunction.

PMID- 19840890
TI  - Sudden deaths following the unexpected demise of a popular politician in India.
AB  - The recent death of a popular politician in India was followed by a spate of
      sudden deaths. In this letter, we analyze the deaths as reported in newspapers,
      and try to arrive at a reason for this strange phenomenon.

PMID- 19840891
TI  - Interpretation of O K-edge EELS in zircon using a structural variation approach.
AB  - This work describes an approach to interpret the near-edge fine structure of
      electron energy-loss spectroscopy (EELS) of O K-edge in zircon using a structural
      variation method. The positions and intensities of several peaks in the O K-edge
      EELS spectrum are assigned to specific structural parameters. It suggests that
      the near-edge structures in EELS can be used to measure atomic structure changes.

PMID- 19840892
TI  - Fatty acid composition of the brain of intrauterine growth retardation rats and
      the effect of maternal docosahexaenoic acid enriched diet.
AB  - AIM: To determine whether the intrauterine environment affects lipid metabolism,
      we measured the fatty acid composition of the brain in rats with intrauterine
      growth retardation (IUGR) induced by synthetic thromboxane A2 (STA2).
      Additionally, we evaluated the effect of maternal docosahexaenoic acid (DHA)
      enriched diet. METHODS: Two experimental diets were provided: soy bean oil and
      DHA-enriched diets. Maternal rats were divided randomly into three groups, STA2
      /Soy (Sham), STA2+/Soy (IUGR), and STA2+/DHA (DHA) groups. The Sham and IUGR
      groups were fed the soy diet, and the DHA group received the DHA-enriched diet
      from embryonic day 7 until delivery. On postnatal days 1 and 7, the pups were
      weighed and their brains were removed for lipid analysis. RESULTS: The body
      weight of the IUGR and DHA groups was significantly less than that of the Sham
      group both on the postnatal days 1 and 7, whereas it was not significantly
      different between the IUGR and DHA groups either on postnatal day 1 or day 7.
      There was no significant difference in the percentage of DHA between the Sham and
      IUGR groups either on postnatal day 1 or 7. On the other hand, the percentage of
      DHA was higher in the DHA group than in the IUGR group both on the postnatal days
      1 and 7. CONCLUSIONS: The fatty acid composition in the brain was not altered in
      the STA2-induced IUGR rat model. Increased DHA percentage was observed in the
      maternal DHA-enriched diet group, although no beneficial effect on body weight
      gain was observed.

PMID- 19840894
TI  - Sensitivity of the female rat to olanzapine-induced weight gain--far from the
      clinic?

PMID- 19840893
TI  - Recent advances in brain-machine interfaces.

PMID- 19840896
TI  - Five-year stability of ICD-10 diagnoses among Chinese patients presented with
      first-episode psychosis in Hong Kong.
AB  - BACKGROUND: Diagnostic stability is one measure of predictive validity for
      psychiatric syndromes. It is an under-studied area in functional psychosis
      despite its clinical and research implications. We aimed at evaluating the
      stability of ICD-10 diagnoses in a sample of young people with first-episode
      psychosis. METHOD: One hundred and sixty-six Hong Kong Chinese enrolled in a
      regional first-episode psychosis treatment program were studied. Subjects'
      baseline and final 5-year consensus diagnoses were established via systematic
      medical records' review to determine diagnostic stability and to identify
      predictors of diagnostic shift towards schizophrenia spectrum. RESULTS: The
      overall diagnostic consistency was 80.7%. Bipolar affective disorder and
      schizophrenia were the most stable diagnostic categories over 5 years with
      prospective consistency of 100% and 95.8% respectively. The least stable baseline
      diagnoses were unspecified non-organic psychosis, acute and transient psychotic
      disorders and delusional disorder. Around one-fifth (19.3%) of subjects had
      diagnostic revision in 5 years. The predominant pattern of diagnostic shift was
      towards schizophrenia spectrum disorder. Family history of psychosis and longer
      duration of untreated psychosis were associated with diagnostic transition
      towards schizophrenia spectrum. CONCLUSIONS: Schizophrenia and bipolar affective
      disorder were diagnostically stable and could be reliably classified at intake in
      a Chinese first-episode psychosis sample using the ICD-10 criteria. Diagnostic
      instability in the least prevalent categories of functional psychosis highlights
      the limitations of current taxonomies and calls for ongoing revision of
      diagnostic criteria. In the absence of biological marker, longitudinal validation
      across consecutive episodes is necessary for accurate diagnostic ascertainment.

PMID- 19840895
TI  - Verbal fluency deficits and altered lateralization of language brain areas in
      individuals genetically predisposed to schizophrenia.
AB  - Alterations of verbal fluency may correlate with deficits of gray matter volume
      and hemispheric lateralization of language brain regions like the pars
      triangularis (PT) in schizophrenia. Examining non-psychotic individuals at high
      genetic risk (HR) for schizophrenia may clarify if these deficits represent
      heritable trait markers or state dependent phenomena. We assessed adolescent and
      young adult HR subjects (N=60) and healthy controls (HC; N=42) using verbal
      fluency tests and Freesurfer to process T1-MRI scans. We hypothesized volumetric
      and lateralization alterations of the PT and their correlation with verbal
      fluency deficits. HR subjects had letter verbal fluency deficits (controlling for
      IQ), left PT deficits (p=.00), (controlling ICV) and reversal of the L>R PT
      asymmetry noted in HC. Right Heschl's (p=.00), left supramarginal (p=.00) and
      right angular gyrii (p=.02) were also reduced in HR subjects. The L>R asymmetry
      of the Heschl's gyrus seen in HC was exaggerated and asymmetries of L>R of
      supramarginal and R>L of angular gyri, seen in HC were attenuated in HR subjects.
      L>R asymmetry of the PT predicted better verbal fluency across the pooled HR and
      HC groups. Young relatives of schizophrenia patients have verbal fluency
      deficits, gray matter volume deficits and reversed asymmetry of the pars
      triangularis. A reversed structural asymmetry of the PT in HR subjects may impair
      expressive language abilities leading to verbal fluency deficits. Volumetric
      deficits and altered asymmetry in inferior parietal and Heschl's gyrii may
      accompany genetic liability to schizophrenia.

PMID- 19840897
TI  - Beyond symptom dimensions: schizophrenia risk factors for patient groups derived
      by latent class analysis.
AB  - INTRODUCTION: Patients grouped by latent class analysis of symptoms show some
      consensus between studies, and may be less etiologically heterogeneous than
      current diagnoses. If so, the effect size of 'neurodevelopmental' risk factors
      may be greater than in equivalent DSMIV diagnostic groups. METHOD: Two hundred
      fifty six individuals with neurodevelopmental risk factors recorded in the
      National Child Development Study (1958) UK birth cohort were grouped by data
      driven illness subtypes, derived previously in over 1000 individuals. The effect
      sizes of these risks were compared between data-derived and DSMIV schizophrenia
      (295.x) groups. RESULTS: Compared to DSMIV schizophrenia, the data-driven subtype
      broadly characterized by the presence of psychotic symptoms in the absence of
      affective symptoms showed significantly greater effect sizes in eight out of
      thirteen continuously-rated risk factors: birth weight, cognition, childhood
      behavioural problems, and neurological softsigns including handedness.
      CONCLUSION: A data-driven subgroup of schizophrenia patients, characterized as
      lacking co-morbid depressive symptoms, is less heterogeneous with respect to
      neurodevelopmental etiology.

PMID- 19840898
TI  - A comparison of insight into clinical symptoms versus insight into neuro
      cognitive symptoms in schizophrenia.
AB  - BACKGROUND: Schizophrenia is associated with neuropsychological deficits that
      have been linked to poor functional outcome. To address this problem,
      pharmacologic and behavioral treatments are being developed for cognitive
      impairments, but they will not be well utilized if people with schizophrenia do
      not perceive a need for treatment. AIMS: This study compared whether people with
      schizophrenia have a similar degree of insight into neuro-cognitive symptoms as
      clinical symptoms, and whether neuro-cognitive and clinical symptoms are
      similarly related to degree of insight into these two aspects of the illness.
      METHOD: Seventy-one patients with schizophrenia were administered measures of
      clinical and neuro-cognitive status as well as clinician rated measures of
      insight into clinical and neuro-cognitive symptoms. RESULTS: Patients had
      significantly less insight into their neuro-cognitive symptoms than their
      clinical symptoms. On average, patients had good insight into clinical symptoms
      and partial insight into neuro-cognitive symptoms. Neuropsychological variables
      were related to insight into clinical symptoms, but not insight into neuro
      cognition. Clinical variables were not significantly related to either type of
      insight. CONCLUSIONS: Insight is not a unitary concept and the differences
      between awareness of neuro-cognition and awareness of clinical symptoms suggest
      that they have to be addressed separately in treatment. Specific education about
      cognitive symptoms may be necessary to improve awareness of this aspect of the
      schizophrenia.

PMID- 19840899
TI  - Antibacterial, antifungal, and antiviral activities of some flavonoids.
AB  - Antibacterial and antifungal activities of six plant-derived flavonoids
      representing two different structural groups were evaluated against standard
      strains of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis,
      Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus,
      Enterococcus faecalis, Bacillus subtilis and their drug-resistant isolates, as
      well as fungi (Candida albicans, C. krusei) using the microdilution broth method.
      Herpes simplex virus Type-1 and Parainfluenza-3 virus were employed for antiviral
      assessment of the flavonoids using Madin-Darby bovine kidney and Vero cell lines.
      Ampicillin, gentamycin, ofloxacin, levofloxacin, fluconazole, ketoconazole,
      acyclovir, and oseltamivir were used as the control agents. All tested compounds
      (32-128 microg/ml) showed strong antimicrobial and antifungal activities against
      isolated strains of P. aeruginosa, A. baumanni, S. aureus, and C. krusei. Rutin,
      5,7-dimethoxyflavanone-4'-O-beta-D-glucopyranoside and 5,7,3'-trihydroxy
      flavanone-4'-O-beta-D-glucopyranoside (0.2-0.05 microg/ml) were active against PI
      3, while 5,7-dimethoxyflavanone-4'-O-[2''-O-(5'''-O-trans-cinnamoyl)-beta-D
      apiofuranosyl]-beta-D-glucopyranoside (0.16-0.2 microg/ml) inhibited potently HSV
      1.

PMID- 19840900
TI  - Characterization of a stream sediment matrix material for sampling behavior in
      order to use it as a CRM.
AB  - Sampling behavior of multielements in a stream sediment matrix was studied with
      sample sizes in a range of 9 orders of magnitude by a combination of INAA, PIXE
      and SR-XRF. For accurately weighable sample sizes (>1mg), sampling uncertainties
      for 16 elements are better than 1% by INAA. For sample sizes that cannot be
      accurately weighed (<1mg), PIXE and SR-XRF were used and the effective sample
      sizes were estimated. Sampling uncertainties for seven elements are better than
      1% at sample sizes of tenth mg level, and that for three elements are better than
      10% on ng levels.

PMID- 19840901
TI  - In search of an ecological dosimeter for high dose measurements Aqueous sucrose
      solutions.
AB  - The purpose of this work was to study physico-chemical changes in irradiating
      aqueous sucrose solutions from the point of view of their usefulness for
      technological dosimetry. Non-irradiated sucrose solutions are optically "empty"
      in the visible and near UV range. After gamma irradiation an absorption band with
      a maximum at 263 nm appears. It was confirmed that this band can be used as
      dosimetric signal for the dose range: 1-10 kGy. The species responsible for the
      263 nm band is a neutral product of sucrose oxidation by an OH radical. High
      energy electron irradiation creates another UV absorbing species with the
      absorption band peaked at 270 nm. Further investigations are necessary to
      establish to what extent it can be used for electron beam dosimetry.

PMID- 19840902
TI  - Breast cancer care in the Canada and the United States: ecological comparisons of
      extremely impoverished and affluent urban neighborhoods.
AB  - This study examined the differential effect of extreme impoverishment on breast
      cancer care in urban Canada and the United States. Ontario and California
      registry-based samples diagnosed between 1998 and 2000 were followed until 2006.
      Extremely poor and affluent neighborhoods were compared. Poverty was associated
      with non-localized disease, surgical and radiation therapy (RT) waits, non
      receipt of breast conserving surgery, RT and hormonal therapy, and shorter
      survival in California, but not in Ontario. Extremely poor Ontario women were
      consistently advantaged on care indices over their California counterparts. More
      inclusive health insurance coverage in Canada seems the most plausible
      explanation for such Canadian breast cancer care advantages.

PMID- 19840903
TI  - Seeking affective health care: Korean immigrants' use of homeland medical
      services.
AB  - This paper explores the phenomenon of migrants returning to their country of
      origin for health care. Specifically, it examines the case of Korean immigrants
      to New Zealand making trips to their homeland to obtain medical operations. We
      situate our inquiry at the intersection of literatures on home, therapeutic
      spaces and health care consumption. Using semi-structured in-depth interviews we
      focus on the question of why and how first-generation Koreans in Auckland, New
      Zealand, seek medical services in their country of birth. Narratives suggest that
      the immigrants' decisions are shaped by interactions between agency (self) and
      structure (society) that occur across transnational social fields. Strong
      preferences for decisive and comprehensive treatment in culturally comfortable
      settings are revealed. The study highlights a particular link between health and
      place: that if financially able, immigrant patients will seek not only effective,
      but also affective medical care.

PMID- 19840904
TI  - Serum BAFF and APRIL levels in patients with PBC.
AB  - B-cell-activating factor belonging to the TNF family (BAFF) and a proliferation
      inducing ligand (APRIL) are known to be involved in the occurrence of autoimmune
      diseases. We assessed serum levels of these cytokines in PBC patients. Serum BAFF
      levels were significantly higher in PBC patients than in healthy controls
      (1253.9+/-741.4 vs. 722.8+/-199.2 pg/ml; p<0.0001) and HCV-infected patients
      (1253.9+/-741.4 vs. 871.0+/-251.1 pg/ml; p=0.015). Whereas changes in serum APRIL
      levels were not significant among these groups, there was a significant
      correlation between BAFF and AST (R=0.278, p=0.003) or total bilirubin (R=0.363,
      p=0.0006) in PBC patients. Furthermore, serum BAFF levels were elevated in PBC
      patients with advanced interface hepatitis. Our data indicate that serum levels
      of BAFF and APRIL are differentially regulated and serum BAFF levels are
      significantly elevated in PBC patients. These findings suggest that BAFF may
      serve as a modulator of the clinical and/or serological manifestation in PBC
      patients.

PMID- 19840906
TI  - Electron transfer process from marine biofilms to graphite electrodes in
      seawater.
AB  - It is known that electron transfer processes exist between microorganisms and
      electrodes. Many anaerobic bacteria, which can transfer electrons to solid
      electrodes, had been identified. However, little attention has been paid to the
      interactions between aerobic biofilms and electrodes. In this study, marine
      biofilms formation on graphite electrodes was characterized by open circuit
      potential and field emission scanning electron microscopy. Electron transfer
      between marine aerobic biofilms and graphite electrodes was investigated
      primarily by cyclic voltammograms and electrochemical impedance spectroscopy
      techniques. Herein, we suggest that marine biofilms are a kind of conductive
      biofilms that can transfer electrons to graphite electrodes under anaerobic and
      aerobic conditions. Some cytochrome species in bacterial biofilms may play a key
      role in the electron transfer process.

PMID- 19840905
TI  - Do copper ions activate tyrosinase enzyme? A biosensor model for the solution.
AB  - Some metal ions play a cofactor role for the activity of tyrosinase enzyme and
      one of them is copper ion. In this study an amperometric biosensor was developed
      in order to investigate the effect of the copper ions on the activity of
      tyrosinase enzyme. In the construction of the biosensor tyrosinase enzyme was
      immobilized on a Clark-type dissolved oxygen probe which was covered with a
      oxygen sensitive teflon membrane, by using a chemical covalent immobilization
      method based on gelatine and bifunctional reagent, glutaraldehyde. The principle
      of the measurement was based on the determination of the differentiation of
      dissolved oxygen level in the enzymatic reaction catalyzed by tyrosinase in the
      absence and the presence of copper ions. Differences between the dissolved oxygen
      concentrations were related to copper ion concentration which was added in to the
      reaction medium. The biosensor response depends linearly on copper ion
      concentration between 2.5-20.0microM with a response time 1min. The detection
      limit of the biosensor is 0.95microM. In the optimization studies of the
      biosensor, the most suitable amounts of tyrosinase, gelatin and glutaraldehyde
      ratio were determined to be 69.0U/cm(-2), 4.21mg/cm(-2), and 2.5%, respectively.
      In the optimization studies of the biosensor, phosphate buffer (pH 7.0 ,50mM) and
      30 degrees C were detected to be working conditions. For the characterization of
      the biosensor some parameters such as reproducibility, thermal and pH stability
      were carried out.

PMID- 19840907
TI  - [Early neurological symptoms in patients with incontinentia pigmenti].

PMID- 19840908
TI  - SVR versus neural-fuzzy network controllers for the sagittal balance of a biped
      robot.
AB  - The real-time balance control of an eight-link biped robot using a zero moment
      point (ZMP) dynamic model is difficult due to the processing time of the
      corresponding equations. To overcome this limitation, two alternative intelligent
      computing control techniques were compared: one based on support vector
      regression (SVR) and another based on a first-order Takagi-Sugeno-Kang (TSK)-type
      neural-fuzzy (NF) network. Both methods use the ZMP error and its variation as
      inputs and the output is the correction of the robot's torso necessary for its
      sagittal balance. The SVR and the NF were trained based on simulation data and
      their performance was verified with a real biped robot. Two performance indexes
      are proposed to evaluate and compare the online performance of the two control
      methods. The ZMP is calculated by reading four force sensors placed under each
      robot's foot. The gait implemented in this biped is similar to a human gait that
      was acquired and adapted to the robot's size. Some experiments are presented and
      the results show that the implemented gait combined either with the SVR
      controller or with the TSK NF network controller can be used to control this
      biped robot. The SVR and the NF controllers exhibit similar stability, but the
      SVR controller runs about 50 times faster.

PMID- 19840909
TI  - Compression quality prediction model for JPEG2000.
AB  - A compression quality prediction model is proposed for grey images coding with
      JPEG2000. With this model, the compression quality (PSNR) could be estimated
      according to the given compression ratio (CR) and the image activity measures
      (IAM) without coding images. The image activity measure is the weighted sum of
      the IAM values based on the 1-pixel-distance and 2-pixel-distance gradients along
      horizontal and vertical directions. We have shown that IAM is a function of the
      image variance and autocorrelation coefficients. Based on Shannon's rate
      distortion theorem, a theoretical justification is provided for the correlation
      of IAM with PSNR. Experimental results show that the prediction error is lower
      than 1 dB for more than 70% sample images when CR is higher than 15. The
      prediction error is less than 2 dB for over 90% images. This prediction
      performance is acceptable for general applications.

PMID- 19840910
TI  - On the total variation dictionary model.
AB  - The goal of this paper is to provide a theoretical study of a total variation
      (TV) dictionary model. Based on the properties of convex analysis and bounded
      variation functions, the existence of solutions of the TV dictionary model is
      proved. We then show that the dual form of the model can be given by the
      minimization of the sum of the l(1) -norm of the dual solution and the Bregman
      distance between the curvature of the primal solution and the subdifferential of
      TV norm of the dual solution. This theoretical result suggests that the
      dictionary must represent sparsely the curvatures of solution image in order to
      obtain a better denoising performance.

PMID- 19840911
TI  - Squigraphs for fine and compact modeling of 3-D shapes.
AB  - We propose to superpose global topological and local geometric 3-D shape
      descriptors in order to define one compact and discriminative representation for
      a 3-D object. While a number of available 3-D shape modeling techniques yield
      satisfactory object classification rates, there is still a need for a refined and
      efficient identification/recognition of objects among the same class. In this
      paper, we use Morse theory in a two-phase approach. To ensure the invariance of
      the final representation to isometric transforms, we choose the Morse function to
      be a simple and intrinsic global geodesic function defined on the surface of a 3
      D object. The first phase is a coarse representation through a reduced
      topological Reeb graph. We use it for a meaningful decomposition of shapes into
      primitives. During the second phase, we add detailed geometric information by
      tracking the evolution of Morse function's level curves along each primitive. We
      then embed the manifold of these curves into [Formula: see text], and obtain a
      single curve. By combining phase one and two, we build new graphs rich in
      topological and geometric information that we refer to as squigraphs. Our
      experiments show that squigraphs are more general than existing techniques. They
      achieve similar classification rates to those achieved by classical shape
      descriptors. Their performance, however, becomes clearly superior when finer
      classification and identification operations are targeted. Indeed, while other
      techniques see their performances dropping, squigraphs maintain a performance
      rate of the order of 97%.

PMID- 19840913
TI  - Localization and recovery of peripheral neural sources with beamforming
      algorithms.
AB  - The peripheral nervous system carries sensory and motor information that could be
      useful as command signals for function restoration in areas such as neural
      prosthetics and functional electrical stimulation (FES). Nerve cuff electrodes
      provide a robust and safe technique for recording nerve signals. However, a
      method to separate and recover signals from individual fascicles is necessary.
      Prior knowledge of the electrode geometry was used to develop an algorithm which
      assumes neither signal independence nor detailed knowledge of the nerve's
      geometry/conductivity, and is applicable to any wide-band near-field situation.
      When used to recover fascicular activities from simulated nerve cuff recordings
      in a realistic human femoral nerve model, this beamforming algorithm separates
      signals as close as 1.5 mm with cross-correlation coefficient, R > 0.9 (10%
      noise). Ten simultaneous signals could be recovered from individual fascicles
      with only a 20% decrease in R compared to a single signal. At high noise levels
      (40%), sources were localized to 180 +/- 170 microm in the 12 x 3 mm cuff.
      Localizing sources and using the resulting positions in the recovery algorithm
      yielded R = 0.66 +/- 0.10 in 10% noise for five simultaneous muscle-activation
      signals from synergistic fascicles. These recovered signals should allow natural,
      robust, closed-loop control of multiple degree-of-freedom prosthetic devices and
      FES systems.

PMID- 19840914
TI  - Effect of bipolar cuff electrode design on block thresholds in high-frequency
      electrical neural conduction block.
AB  - Many medical conditions are characterized by undesired or pathological peripheral
      neurological activity. The local delivery of high-frequency alternating currents
      (HFAC) has been shown to be a fast acting and quickly reversible method of
      blocking neural conduction and may provide a treatment alternative for
      eliminating pathological neural activity in these conditions. This work
      represents the first formal study of electrode design for high-frequency nerve
      block, and demonstrates that the interpolar separation distance for a bipolar
      electrode influences the current amplitudes required to achieve conduction block
      in both computer simulations and mammalian whole nerve experiments. The minimal
      current required to achieve block is also dependent on the diameter of the fibers
      being blocked and the electrode-fiber distance. Single fiber simulations suggest
      that minimizing the block threshold can be achieved by maximizing both the
      bipolar activating function (by adjusting the bipolar electrode contact
      separation distance) and a synergistic addition of membrane sodium currents
      generated by each of the two bipolar electrode contacts. For a rat sciatic nerve,
      1.0-2.0 mm represented the optimal interpolar distance for minimizing current
      delivery.

PMID- 19840916
TI  - [Roger David Kornberg].

PMID- 19840915
TI  - No evidence for fetal microchimerism in the skin of patients with pemphigoid
      gestationis.

PMID- 19840917
TI  - [Progress of adaptive immunity system of agnathan vertebrates].
AB  - Extant jawless vertebrates, represented by lampreys and hagfishes, have innate
      immune receptors with variable domains structurally resembling T/B-cell
      receptors. However, they lack cardinal elements of adaptive immunity shared by
      all jawed vertebrates: T/B-cell receptors and major histocompatibility complex
      molecules. Thus, it is widely believed that adaptive immunity is unique to jawed
      vertebrates. Recently, this belief was overturned by the discovery of agnathan
      antigen receptors, known as variable lymphocyte receptors. These receptors
      generate diversity in their antigen-binding sites through assembling highly
      diverse leucine-rich repeat modules. The crystal structures of hagfish variable
      lymphocyte receptor monomers indicate that they adopt a horseshoe-shaped
      structure and likely bind antigens through the hypervariable concave surface.
      Secreted variable lymphocyte receptors form pentamers or tetramers of dimers bind
      antigens with high specificity and avidity. This indicates that jawed and jawless
      vertebrates have developed antigen receptors independently. This paper provides
      valuable clues for studying the origin and evolution of adaptive immunity system.

PMID- 19840918
TI  - [Polycomb group protein complexes].
AB  - The transcriptional repressors of the polycomb group (PcG) proteins regulate the
      targeted genes expression through chromatin modifications. They can be separated
      biochemically and functionally into two major core multiprotein complexes: PRC1
      (Polycomb repressive complex 1) and PRC2 (Polycomb repressive complex 2). Studies
      revealed that PcG proteins were not only crucial for correct execution of
      developmental programs but also involved in the regulation of cell proliferation,
      differentiation, and tumorigenesis. This paper summarizes the components of PcG
      proteins complexes, its silencing mechanisms and biological functions, and
      discusses the study of PcG proteins in future.

PMID- 19840919
TI  - [Research progress in ARF-GEF gene family].
AB  - ARF-GEFs are a family of guanine-nucleotide exchange factors catalyzing the
      exchange of GDP for GTP on ADP-ribosylation factor. Large ARF-GEFs are highly
      conserved in all eukaryotes. It is an important regulator in both membrane
      dynamics and protein trafficking. Significant progress has been made in
      elucidating the structure, subcellular localization, and physiological functions
      of ARF-GEFs as a hot topic of cell biology recently. In this review, the
      character-istics and distribution of ARF-GEFs in different species, and recent
      research progress of ARF-GEFs and their regulation system are summarized.

PMID- 19840920
TI  - [Progress in regulation of activity and stability of ubiquitin protein ligase
      MDM2].
AB  - The ubiquitin protein ligase (E3) MDM2 (Murine double minute 2) possesses
      oncogenic activities. Overexpression of this protein enhances degradation and
      inactivation of the tumor suppressor p53. At least 7% of all human tumors exhibit
      inappropriate amplification of mdm2, whereas p53 gene remains in its wild-type
      configuration. This indicates that MDM2 may function in the p53-independent
      manner to promote tumorigenesis. Considering the critical role of MDM2, this
      review summarizes the current mechanisms and progress on MDM2 regulation in
      levels of gene control, mRNA transcription, post-translational modification, and
      interaction proteins.

PMID- 19840921
TI  - [Advance on the cloning and functional analysis of disease resistance genes in
      rice].
AB  - Improving the disease resistance of rice is a major objective in rice breeding
      programs, which provides a basic guarantee for the good quality and high yield in
      rice. Recently, substantial progresses on the research of rice disease resistant
      mechanism had been made. Some important genes had been identified and cloned. The
      recent achievements in identification, cloning, and biological function analyses
      of these genes were summarized and their potential application in breeding was
      also discussed.

PMID- 19840922
TI  - [SNPs detection of adiponectin gene and its relationship with carcass and meat
      quality traits in Qinchuan cattle].
AB  - Four hundred and five Qinchuan cattle at the age of 24 months were used to detect
      SNPs of adiponectin gene by PCR-SSCP and sequencing technology and to analyze the
      correlation of SNPs with carcass and meat quality traits using the general linear
      model (GLM) in SPSS program. Five genotypes (AA, AB, BB, CC, CD) were
      detected,with one G-->C mutation at 64 bp in exon2 of adiponectin in ABBB
      genotypes and one C-->T mutation at 50 bp in exon3 of adiponectin in CD genotype.
      G-->C mutation resulted glutamic acid (GGA) into glutamine (GCA) and C-->T
      mutation resulted serine (TCA) into leucine (TTA). Statistical analysis revealed
      that Qinchuan cattle with AA genotype was higher than BB genotype in slaughter
      weight, back fat thickness, carcass weight, loin muscle area (P < 0.05). The
      crural girth of AA genotype was significantly higher than AB and BB genotypes (P
      < 0.01). Qinchuan cattle with CD genotype was higher than CC genotype in
      slaughter weight, subcutaneous fat thickness, back fat thickness, crural girth,
      and tenderness (P < 0.05). Adiponectin gene was proved to be closely related to
      carcass and meat quality traits (P < 0.05), which can be used as a candidate
      molecular marker for production of high-grade meat in Qinchuan beef cattle.

PMID- 19840923
TI  - [Methylation status of pig adiponectin promoter and its expression].
AB  - Adiponectin, a cytokine hormone secreted exclusively by adipose tissue, has key
      roles in energy homeostasis and in metabolism of glucose and lipid. Adiponectin
      expression was negatively associated with obesity. Many CpG sites were found at
      the adiponectin promoter region (nucleotides -1500 approximately -1350 bp). To
      further understand the regulation of pig adiponectin expression, the methylation
      status of pig adiponectin promoter and its mRNA expression were analyzed by
      methylation special PCR (MSP) and real-time PCR. At the adiponectin promoter
      region where CG enriches (nucleotides -1500 approximately -1350 bp), the
      percentage of demethylation in Changbai pigs was 83%; and the percentages of
      demethylation in Lantang pigs at 90-day-old and adult stages were 33% and 100%,
      respectively. The process of methylation and demethyla-tion mainly occurred in
      certain CpG sites. In muscle tissues, the promoter hypermethylation status of
      adiponectin gene was detected, which was consistent with the expression of this
      gene. These results suggested that the methylation of this gene experienced a
      dynamic process, with the development of individuals, which agreed with the
      fluctuating trend of gene expression.

PMID- 19840924
TI  - [Genomic structure of DAA gene and polymorphism within MHC-DAA alleles in
      Japanese flounder (Paralichthys olivaceus)].
AB  - To investigate the allele polymorphism of MHC-DAA in Japanese flounder
      (Paralichthys olivaceus), specific primers were designed based on the published
      DAA-cDNA sequence of P. olivaceus to amplify the entire introns from flounder.
      Gene DAA consisted of four exons and three introns. The exon-intron structure was
      similar as that of Atlantic salmon. A polymorphic microsatellite was detected in
      intron 2. Subsequently, specific primer was designed based on the DAA genomic
      sequences. The genetic polymorphism within exon 2 of MHC-DAA was investigated by
      means of sequence analysis. Forty-five individuals were selected to amplify exon
      2 and intron 2. One hundred and twenty-nine fragments revealed 30 novel alleles
      belonging to 18 allele major type. The frequency of alleles and the numbers of
      subtypes were not distributed equally. There were 55 variable sites in exon 2.
      The diversity of nucleotide within the sequence of exon 2 was 0.0887. The
      nucleotide sequence was corresponded with a putative peptide. Among the 83 amino
      acids in this peptide, 37.80% were variable, and 30 parsimony informative sites
      were observed. The rates of non-synonymous substitution (dN) were 3.30 and 2.43
      times higher than the rate of synonymous substitution (dS) in the peptide-binding
      regions (PBR) and non-PBR, respectively. In this study, the high ratio of dN/dS
      value and high allelic diversity observed in flounder suggested a balancing
      selection in the exon2 of the MHC class IIA gene, which explained the high
      polymorphism of MHC-DAA gene in Paralichthys olivaceus.

PMID- 19840925
TI  - [Cloning of the promoter region of Leuciscus Merzbacheri beta-actin gene and
      detection of its function].
AB  - To utilize the gene resources of Leuciscus merzbacheri, a 2,398 bp (SZ21) DNA
      fragment including the 5'-flanking region and partial open reading frame of the
      beta-actin gene was obtained through PCR amplification. SZ21 includes a
      regulatory sequence which contains the 5'-proximal promoter, the first, the
      second and the third exons and the partial fourth exon sequence. The 5'-proximal
      promoter region is critical for transcription activity including the CAAT box,
      TATA box and CArG box. The analysis of putative transcription binding sites of
      the promoter by on-line software revealed the presence of the critical
      transcription binding sites (such as E-box, RU49, ZBPF, CEBP and CREB). CMV
      promoter for eukaryote vector pEGFP-N1-AFP III was destroyed by Aat II digestion.
      SZ21 regulatory sequence was inserted into the vector pEGFP-N1-AFP III (with
      destroyed CMV) that can express green fluorescence protein, and beta2 pEGFP-N1
      AFP III recombination vector was constructed. Linearized beta2 pEGFP-N1-AFP III
      was transfected into BHK-21 cell through lipofectin. EGFP expression of the
      transgenic cell was observed by micro fluoroscope. The results indicated that the
      cloned Leuciscus merzbacheri beta-actin gene promoter SZ21 has the activity to
      switch on the EGFP expression in mammal cell, and has a con-tinued starting
      expression activity passing on from generation to generation in green
      fluorescence cell. In addition, the SZ21 target fragment was detected in the BHK
      21 green fluorescence cell genomic DNA by PCR. This suggested that the SZ21
      promoter of beta-actin gene has effective transcription activity and can promote
      the expression of foreign gene.

PMID- 19840926
TI  - [Preliminary studies on the function of Arabidopsis CK1A gene].
AB  - A casein kinase 1 protein gene, CK1A, was isolated from Arabidopsis seedlings by
      RT-PCR method. This gene contains an open reading frame of 2,112 bp, which
      encodes 703 amino acids. The plant expression vector of 35S: GFP: CK1A was
      constructed by the Gateway System. The 35S: GFP: CK1A fusion protein was
      localized to the nucleus in onion epidermal cell, indicating that the product of
      CK1A gene plays a role in the cell nucleus. The semi-quantitative RT-PCR analysis
      showed that CK1A was highly expressed in flowers, stems and roots, but less in
      leaves and leafstalks. The yeast two-hybrid analysis demonstrated that CK1A and
      CRY2 can interact in vivo under blue light, which indicates that CK1A may play an
      important role in blue light signal induction of Arabidopsis.

PMID- 19840927
TI  - [Analysis of cDNA library of Cucumis sativus L. challenged by Pseudomonas
      syringae pv. Lachrymans].
AB  - A cDNA library was constructed from the leaves of the disease-resistant cucumber
      (Cucumis sativus L.) cultivar 'D0462' challenged by Pseudomonas syringae pv.
      Lachrymans for 48 h. The inserted fragment sizes ranged from 0.45 to 2.1 kb and
      the average inserted size was 1 kb. Sequencing analysis showed that 2 352 TUTs
      (Tentative unique transcripts), 282 contigs, and 2 070 singlets were identified
      in the 2 966 ESTs derived from the cDNA library. The result of the BlastX
      analysis indicated that there were 1 848 ESTs with known or unknown function, 504
      ESTs with no significant similarity matching with any protein or DNA sequence in
      the databases. In this library, many defense/disease-resistant related genes,
      such as metallothionein, glutathione S-transferase, ubiquitin, b-1, 3-glucanase,
      zinc finger protein, and cysteine protease, which might participate in the plant
      and the pathogens, are inclued.

PMID- 19840928
TI  - [Phylogenetic analysis of Hystrix and its related genera (Poaceae: Triticeae)
      based on the sequences of the gene encoding 3-phosphoglycerate kinase].
AB  - To estimate the phylogenetic relationships between Hystrix and its related genera
      (Poaceae: Triticeae), the sequences of the single-copy nuclear gene Pgk1 were
      analyzed for five Hystrix taxa, together with three Pseudoroegneria (St) species,
      two Hordeum (H) species, two Psathyrostachys (Ns) species, four Elymus (StH)
      species, five Leymus (NsXm) species, Thinopyrum bessarabicum (E(b)), and
      Lophopyrum elongatum (E(e)). Sequence analysis indicated that an 81bp Stowaway
      insertion occurred in the Pgk1 sequences of L. arenarius and Psa. juncea, and a
      29 bp Copia insertion occurred in the Pgk1 sequences of Hy. duthiei, Hy. duthiei
      ssp. longearistata and L. akmolinensis. Phylogenetic analysis indicated that: (1)
      Hy. patula was closely related to Pseudoroegneria, Hordeum, and Elymus; (2) Hy.
      duthiei, Hy. duthiei ssp. longearistata, Hy. coreana, and Hy. komarovii were
      closely related to Psathyrostachys and Leymus. Based on these results, it is
      reasonable to transfer Hy. patula from Hystrix to Elymus, and to combine Hy.
      duthiei, Hy. duthiei ssp. longearistata, Hy. coreana, and Hy. komarovii into
      Leymus.

PMID- 19840929
TI  - [Molecular cloning and characterization of calcineurin A in Setosphaeria
      turcica].
AB  - A Setosphaeria turcica gene encoding the catalytic subunit of calcineurin was
      cloned using degenerated primers corresponding to conserved domains of Ser/Thr
      protein phosphatases and its complete cDNA (GenBank accession No. EF 407562) was
      obtained with RACE method. It's validated single copied model by southern
      hybridization. Furthermore, the CNA inhibitor Cyclosporin A (CsA) exhibited
      potent antifungal activity against conidial germination and appressorium
      formation of S. turcica. The inhibition ratio was positively correlated to CsA
      concentration. However, appressorium formation was more sensitive than conidium
      germination to the inhibitor at the same concentration. It was suggested that CNA
      might play an important role in the pathogenicity of S. turcica.

PMID- 19840930
TI  - Genetic identification of nascent peptides that induce ribosome stalling.
AB  - Several nascent peptides stall ribosomes during their own translation in both
      prokaryotes and eukaryotes. Leader peptides that induce stalling can regulate
      downstream gene expression. Interestingly, stalling peptides show little sequence
      similarity and interact with the ribosome through distinct mechanisms. To explore
      the scope of regulation by stalling peptides and to better understand the
      mechanism of stalling, we identified and characterized new examples from random
      libraries. We created a genetic selection that ties the life of Escherichia coli
      cells to stalling at a specific site. This selection relies on the natural
      bacterial system that rescues arrested ribosomes. We altered transfer-messenger
      RNA, a key component of this rescue system, to direct the completion of a
      necessary protein if and only if stalling occurs. We identified three classes of
      stalling peptides: C-terminal Pro residues, SecM-like peptides, and the novel
      stalling sequence FXXYXIWPP. Like the leader peptides SecM and TnaC, the
      FXXYXIWPP peptide induces stalling efficiently by inhibiting peptidyl transfer.
      The nascent peptide exit tunnel and peptidyltransferase center are implicated in
      this stalling event, although mutations in the ribosome affect stalling on SecM
      and FXXYXIWPP differently. We conclude that ribosome stalling can be caused by
      numerous sequences and is more common than previously believed.

PMID- 19840931
TI  - Mitochondrial DNA damage initiates a cell cycle arrest by a Chk2-associated
      mechanism in mammalian cells.
AB  - Previous work from our laboratory has focused on mitochondrial DNA (mtDNA) repair
      and cellular viability. However, other events occur prior to the initiation of
      apoptosis in cells. Because of the importance of mtDNA in ATP production and of
      ATP in fuel cell cycle progression, we asked whether mtDNA damage was an upstream
      signal leading to cell cycle arrest. Using quantitative alkaline Southern blot
      technology, we found that exposure to menadione produced detectable mtDNA damage
      in HeLa cells that correlated with an S phase cell cycle arrest. To determine
      whether mtDNA damage was causatively linked to the observed cell cycle arrest,
      experiments were performed utilizing a MTS-hOGG1-Tat fusion protein to target the
      hOGG1 repair enzyme to mitochondria and enhance mtDNA repair. The results
      revealed that the transduction of MTS-hOGG1-Tat into HeLa cells alleviated the
      cell cycle block following an oxidative insult. Furthermore, mechanistic studies
      showed that Chk2 phosphorylation was enhanced following menadione exposure.
      Treatment of the HeLa cells with the hOGG1 fusion protein prior to menadione
      exposure resulted in an increase in the rate of Chk2 dephosphorylation. These
      results strongly support a direct link between mtDNA damage and cell cycle
      arrest.

PMID- 19840932
TI  - miR-146a is critical for endotoxin-induced tolerance: IMPLICATION IN INNATE
      IMMUNITY.
AB  - The human toll-like receptor 4 (TLR4) pathway is activated in response to
      lipopolysaccharide (LPS), and subsequent signal transductions lead to the
      production of cytokines such as tumor necrosis factor-alpha (TNF-alpha) by innate
      immune cells. Defects in innate immune response may contribute to the
      overproduction of TNF-alpha leading to systemic inflammation and diseases. Thus,
      the innate immune response needs to be tightly regulated by elaborate mechanisms
      to control its onset and termination. LPS tolerance is a state of
      hyporesponsiveness to subsequent LPS challenge and is achieved by monocytic cells
      after prolonged exposure to LPS. In this report, kinetics of endotoxin-responsive
      microRNAs expression analysis revealed a unique pattern of gradual increase for
      miR-146a starting 4 h after LPS stimulation in THP-1 cells and continued up to 35
      fold over 24 h. Conversely, TNF-alpha increased up to 4 h and then decreased
      gradually implicating a negative correlation with miR-146a progression. The
      characteristic up-regulation of miR-146a toward subsequent LPS challenge in THP-1
      cells was studied. Strikingly, microRNA expression analysis during the tolerized
      state of THP-1 cells showed only miR-146a overexpression suggesting its important
      role in LPS tolerance. In addition, LPS tolerance was dependent on a LPS-priming
      dose and associated miR-146a up-regulation. LPS-tolerized cells were observed to
      regain responsiveness in TNF-alpha production 22 h after LPS removal correlating
      with a decrease in miR-146a level. Transfection of miR-146a into THP-1 cells
      mimicked LPS priming, whereas transfection of miR-146a inhibitor largely
      abolished LPS tolerance. Thus our studies demonstrated that miR-146a is critical
      for the in vitro monocytic cell-based endotoxin tolerance.

PMID- 19840933
TI  - Aup1-mediated regulation of Rtg3 during mitophagy.
AB  - Mitophagy is an autophagic process that degrades mitochondria by an intracellular
      engulfment that leads to their delivery into the lumen of the cell's hydrolytic
      compartment, such as the lysosome in animal cells or the vacuole in yeast. It is
      hypothesized that such processes serve a quality control function to prevent or
      slow the accumulation of malfunctioning mitochondria, which are thought in turn
      to underlie central aspects of the aging process in eukaryotic organisms. We
      recently identified a conserved mitochondrial protein phosphatase homolog, Aup1,
      which is required for efficient stationary phase mitophagy in yeast. In the
      present report, we demonstrate that the retrograde signaling pathway (RTG) is
      defective in aup1Delta mutants. In agreement with a role for Aup1 in the
      regulation of the RTG pathway, we find that deletion of RTG3, a transcription
      factor that mediates the RTG response, causes a defect in stationary phase
      mitophagy and that deletion of AUP1 leads to changes in Rtg3 phosphorylation
      patterns under these conditions. In addition, we find that mitophagic conditions
      lead to induction of RTG pathway target genes in an Aup1-dependent fashion. Thus,
      our results suggest that the function of Aup1 in mitophagy could be explained
      through its regulation of Rtg3-dependent transcription.

PMID- 19840934
TI  - GRASP65 and GRASP55 sequentially promote the transport of C-terminal valine
      bearing cargos to and through the Golgi complex.
AB  - The Golgi matrix proteins GRASP65 and GRASP55 have recognized roles in
      maintaining the architecture of the Golgi complex, in mitotic progression and in
      unconventional protein secretion whereas, surprisingly, they have been shown to
      be dispensable for the transport of commonly used reporter cargo proteins along
      the secretory pathway. However, it is becoming increasingly clear that many
      trafficking machineries operate in a cargo-specific manner, thus we have
      investigated whether GRASPs may control the trafficking of selected classes of
      cargo. We have taken into consideration the C-terminal valine-bearing receptors
      CD8alpha and Frizzled4 that we show bind directly to the PSD95-DlgA-zo-1 (PDZ)
      domains of GRASP65 and GRASP55. We demonstrate that both GRASPs are needed
      sequentially for the efficient transport to and through the Golgi complex of
      these receptors, thus highlighting a novel role for the GRASPs in membrane
      trafficking. Our results open new perspectives for our understanding of the
      regulation of surface expression of a class of membrane proteins, and suggests
      the causal mechanisms of a dominant form of autosomal human familial exudative
      vitreoretinopathy that arises from the Frizzled4 mutation involving its C
      terminal valine.

PMID- 19840935
TI  - Small RNA-dependent expression of secondary metabolism is controlled by Krebs
      cycle function in Pseudomonas fluorescens.
AB  - Pseudomonas fluorescens CHA0, an antagonist of phytopathogenic fungi in the
      rhizosphere of crop plants, elaborates and excretes several secondary metabolites
      with antibiotic properties. Their synthesis depends on three small RNAs (RsmX,
      RsmY, and RsmZ), whose expression is positively controlled by the GacS-GacA two
      component system at high cell population densities. To find regulatory links
      between primary and secondary metabolism in P. fluorescens and in the related
      species Pseudomonas aeruginosa, we searched for null mutations that affected
      central carbon metabolism as well as the expression of rsmY-gfp and rsmZ-gfp
      reporter constructs but without slowing down the growth rate in rich media.
      Mutation in the pycAB genes (for pyruvate carboxylase) led to down-regulation of
      rsmXYZ and secondary metabolism, whereas mutation in fumA (for a fumarase
      isoenzyme) resulted in up-regulation of the three small RNAs and secondary
      metabolism in the absence of detectable nutrient limitation. These effects
      required the GacS sensor kinase but not the accessory sensors RetS and LadS. An
      analysis of intracellular metabolites in P. fluorescens revealed a strong
      positive correlation between small RNA expression and the pools of 2
      oxoglutarate, succinate, and fumarate. We conclude that Krebs cycle intermediates
      (already known to control GacA-dependent virulence factors in P. aeruginosa)
      exert a critical trigger function in secondary metabolism via the expression of
      GacA-dependent small RNAs.

PMID- 19840936
TI  - Genetic ablation of calcium-independent phospholipase A2{gamma} leads to
      alterations in hippocampal cardiolipin content and molecular species
      distribution, mitochondrial degeneration, autophagy, and cognitive dysfunction.
AB  - Genetic ablation of calcium-independent phospholipase A(2)gamma (iPLA(2)gamma)
      results in profound alterations in hippocampal phospholipid metabolism and
      mitochondrial phospholipid homeostasis resulting in enlarged and degenerating
      mitochondria leading to autophagy and cognitive dysfunction. Shotgun lipidomics
      demonstrated multiple alterations in hippocampal lipid metabolism in
      iPLA(2)gamma(-/-) mice including: 1) a markedly elevated hippocampal cardiolipin
      content with an altered molecular species composition characterized by a shift to
      shorter chain length molecular species; 2) alterations in both choline and
      ethanolamine glycerophospholipids, including a decreased plasmenylethanolamine
      content; 3) increased oxidized phosphatidylethanolamine molecular species; and 4)
      an increased content of ceramides. Electron microscopic examination demonstrated
      the presence of enlarged heteromorphic lamellar structures undergoing
      degeneration accompanied by the presence of ubiquitin positive spheroid inclusion
      bodies. Purification of these enlarged heteromorphic lamellar structures by
      buoyant density centrifugation and subsequent SDS-PAGE and proteomics identified
      them as degenerating mitochondria. Collectively, these results identify the
      obligatory role of iPLA(2)gamma in neuronal mitochondrial lipid metabolism and
      membrane structure demonstrating that iPLA(2)gamma loss of function results in a
      mitochondrial neurodegenerative disorder characterized by degenerating
      mitochondria, autophagy, and cognitive dysfunction.

PMID- 19840938
TI  - From the gamma-glutamyl cycle to the glycan cycle: a road with many turns and
      pleasant surprises.

PMID- 19840937
TI  - Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling
      cascades distinct from cell surface counterparts.
AB  - G-protein-coupled receptors are thought to transmit extracellular signals to the
      cytoplasm from their position on the cell surface. Some receptors, including the
      metabotropic glutamate receptor 5 (mGluR5), are also highly expressed on
      intracellular membranes where they serve unknown functions. Here, we show that
      activation of cell surface versus intracellular mGluR5 results in unique Ca(2+)
      signatures leading to unique cellular responses. Specifically, activation of
      either cell surface or intracellular mGluR5 leads to JNK, Ca(2+)/calmodulin
      dependent protein kinase (CaMK), and cyclic adenosine 3',5'-monophosphate
      responsive element-binding protein phosphorylation, whereas activation of only
      intracellular mGluR5 leads to ERK1/2 and Elk-1 phosphorylation. Using
      pharmacological and genetic approaches, the present findings support a role for
      CaMK kinase in mediating mGluR5-dependent cyclic adenosine 3',5'-monophosphate
      responsive element-binding protein phosphorylation, whereas CaMKII is upstream of
      intracellular mGluR5-mediated Elk-1 phosphorylation. Consistent with models
      showing Elk-1 regulating cascades of gene expression, the known Elk-1 targets c
      fos and egr1 were up-regulated following intracellular mGluR5 activation, whereas
      a representative non-Elk-1 target, c-jun, was not. These findings emphasize that
      glutamate not only serves as a neurotransmitter for cell surface receptors but,
      when transported into the cell, can also activate intracellular receptors such as
      mGluR5. Glutamate activation of intracellular mGluR5 serves an important role in
      the regulation of nuclear Ca(2+), transcriptional activation, and gene expression
      necessary for physiological processes such as synaptic plasticity.

PMID- 19840940
TI  - Transglutaminase 2 regulates the GTPase-activating activity of Bcr.
AB  - Transglutaminase 2 (TG2) is a multifunctional protein that has been implicated in
      numerous pathologies including that of neurodegeneration and celiac disease, but
      the molecular interactions that mediate its diverse activities are largely
      unknown. Bcr and the closely related Abr negatively regulate the small G-protein
      Rac: loss of their combined function in vivo results in increased reactivity of
      innate immune cells. Bcr and Abr are GTPase-activating proteins that catalyze the
      hydrolysis of the GTP bound to Rac. However, how the Bcr and Abr GTPase
      activating activity is regulated is not precisely understood. We here report a
      novel mechanism of regulation through direct protein-protein interaction with
      TG2. TG2 bound to the Rac-binding pocket in the GTPase-activating domains of Bcr
      and Abr, blocked Bcr activity and, through this mechanism, increased levels of
      active GTP-bound Rac and EGF-stimulated membrane ruffling. TG2 exists in at least
      two different conformations. Interestingly, experiments using TG2 mutants showed
      that Bcr exhibits preferential binding to the non-compacted conformation of TG2,
      in which its catalytic domain is exposed, but transamidation is not needed for
      the interaction. Thus, TG2 regulates levels of cellular GTP-bound Rac and actin
      cytoskeletal reorganization through a new mechanism involving direct inhibition
      of Bcr GTPase-activating activity.

PMID- 19840939
TI  - Mechanical loading regulates NFATc1 and beta-catenin signaling through a GSK3beta
      control node.
AB  - Mechanical stimulation can prevent adipogenic and improve osteogenic lineage
      allocation of mesenchymal stem cells (MSC), an effect associated with the
      preservation of beta-catenin levels. We asked whether mechanical up-regulation of
      beta-catenin was critical to reduction in adipogenesis as well as other
      mechanical events inducing alternate MSC lineage selection. In MSC cultured under
      strong adipogenic conditions, mechanical load (3600 cycles/day, 2% strain)
      inactivated GSK3beta in a Wnt-independent fashion. Small interfering RNA
      targeting GSK3beta prevented both strain-induced induction of beta-catenin and an
      increase in COX2, a factor associated with increased osteoprogenitor phenotype.
      Small interfering RNA knockdown of beta-catenin blocked mechanical reduction of
      peroxisome proliferator-activated receptor gamma and adiponectin, implicating
      beta-catenin in strain inhibition of adipogenesis. In contrast, the effect of
      both mechanical and pharmacologic inhibition of GSK3beta on the putative beta
      catenin target, COX2, was unaffected by beta-catenin knockdown. GSK3beta
      inhibition caused accumulation of nuclear NFATc1; mechanical strain increased
      nuclear NFATc1, independent of beta-catenin. NFATc1 knockdown prevented
      mechanical stimulation of COX2, implicating NFATc1 signaling. Finally, inhibition
      of GSK3beta caused association of RNA polymerase II with the COX2 gene,
      suggesting transcription initiation. These results demonstrate that mechanical
      inhibition of GSK3beta induces activation of both beta-catenin and NFATc1
      signaling, limiting adipogenesis via the former and promoting osteoblastic
      differentiation via NFATc1/COX2. Our novel findings suggest that mechanical
      loading regulates mesenchymal stem cell differentiation through inhibition of
      GSK3beta, which in turn regulates multiple downstream effectors.

PMID- 19840941
TI  - The mannitol operon repressor MtlR belongs to a new class of transcription
      regulators in bacteria.
AB  - Many bacteria express phosphoenolpyruvate-dependent phosphotransferase systems
      (PTS). The mannitol-specific PTS catalyze the uptake and phosphorylation of d
      mannitol. The uptake system comprises several genes encoded in the single operon.
      The expression of the mannitol operon is regulated by a proposed transcriptional
      factor, mannitol operon repressor (MtlR) that was first studied in Escherichia
      coli. Here we report the first crystal structures of MtlR from Vibrio
      parahemeolyticus (Vp-MtlR) and its homolog YggD protein from Shigella flexneri
      (Sf-YggD). MtlR and YggD belong to the same protein family (Pfam05068). Although
      Vp-MtlR and Sf-YggD share low sequence identity (22%), their overall structures
      are very similar, representing a novel all alpha-helical fold, and indicate
      similar function. However, their lack of any known DNA-binding structural motifs
      and their unfavorable electrostatic properties imply that MtlR/YggD are unlikely
      to bind a specific DNA operator directly as proposed earlier. This structural
      observation is further corroborated by in vitro DNA-binding studies of E. coli
      MtlR (Ec-MtlR), which detected no interaction of Ec-MtlR with the well
      characterized mannitol operator/promoter region. Therefore, MtlR/YggD belongs to
      a new class of transcription factors in bacteria that may regulate gene
      expression indirectly as a part of a larger transcriptional complex.

PMID- 19840942
TI  - A common mutation in paraoxonase-2 results in impaired lactonase activity.
AB  - Paraoxonases (PONs) are a family of lactonases with promiscuous enzyme activity
      that has been implicated in multiple diseases. PON2 is intracellularly located,
      is the most ubiquitously expressed PON, and has the highest lactonase activity of
      the PON family members. Whereas some single-nucleotide polymorphisms (SNPs) in
      PON1 have resulted in altered enzymatic activity in serum, to date the functional
      consequences of SNPs on PON2 function remain unknown. We hypothesized that a
      common PON2 SNP would result in impaired lactonase activity. Substitution of
      cysteine for serine at codon 311 in recombinant PON2 resulted in normal protein
      production and localization but altered glycosylation and decreased lactonase
      activity. Moreover, we screened 200 human lung samples for the PON2 Cys(311)
      variant and found that in vivo this mutation impaired lactonase activity. These
      data suggest that impaired lactonase activity may play a role in innate immunity,
      atherosclerosis, and other diseases associated with the PON2 311 SNP.

PMID- 19840943
TI  - Epidermal growth factor receptor translocation to the mitochondria: regulation
      and effect.
AB  - Co-overexpression of the epidermal growth factor (EGF) receptor (EGFR) and c-Src
      frequently occurs in human tumors and is linked to enhanced tumor growth. In
      experimental systems this synergistic growth requires EGF-dependent association
      of c-Src with the EGFR and phosphorylation of Tyr-845 of the receptor by c-Src. A
      search for signaling mediators of Tyr(P)-845 revealed that mitochondrial
      cytochrome c oxidase subunit II (CoxII) binds EGFR in a Tyr(P)-845- and EGF
      dependent manner. In cells this association involves translocation of EGFR to the
      mitochondria, but regulation of this process is ill-defined. The current study
      demonstrates that c-Src translocates to the mitochondria with similar kinetics as
      EGFR and that the catalytic activity of EGFR and c-Src as well as endocytosis and
      a mitochondrial localization signal are required for these events. CoxII can be
      phosphorylated by EGFR and c-Src, and EGF stimulation reduces Cox activity and
      cellular ATP, an event that is dependent in large part on EGFR localized to the
      mitochondria. These findings suggest EGFR plays a novel role in modulating
      mitochondrial function via its association with, and modification of CoxII.

PMID- 19840944
TI  - Cation-independent mannose 6-phosphate receptor: a composite of distinct
      phosphomannosyl binding sites.
AB  - The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR), which
      contains multiple mannose 6-phosphate (Man-6-P) binding sites that map to domains
      3, 5, and 9 within its 15-domain extracytoplasmic region, functions as an
      efficient carrier of Man-6-P-containing lysosomal enzymes. To determine the types
      of phosphorylated N-glycans recognized by each of the three carbohydrate binding
      sites of the CI-MPR, a phosphorylated glycan microarray was probed with truncated
      forms of the CI-MPR. Surface plasmon resonance analyses using lysosomal enzymes
      with defined N-glycans were performed to evaluate whether multiple domains are
      needed to form a stable, high affinity carbohydrate binding pocket. Like domain
      3, adjacent domains increase the affinity of domain 5 for phosphomannosyl
      residues, with domain 5 exhibiting approximately 60-fold higher affinity for
      lysosomal enzymes containing the phosphodiester Man-P-GlcNAc when in the context
      of a construct encoding domains 5-9. In contrast, domain 9 does not require
      additional domains for high affinity binding. The three sites differ in their
      glycan specificity, with only domain 5 being capable of recognizing Man-P-GlcNAc.
      In addition, domain 9, unlike domains 1-3, interacts with Man(8)GlcNAc(2) and
      Man(9)GlcNAc(2) oligosaccharides containing a single phosphomonoester. Together,
      these data indicate that the assembly of three unique carbohydrate binding sites
      allows the CI-MPR to interact with the structurally diverse phosphorylated N
      glycans it encounters on newly synthesized lysosomal enzymes.

PMID- 19840945
TI  - N-terminal domains elicit formation of functional Pmel17 amyloid fibrils.
AB  - Pmel17 is a transmembrane protein that mediates the early steps in the formation
      of melanosomes, the subcellular organelles of melanocytes in which melanin
      pigments are synthesized and stored. In melanosome precursor organelles,
      proteolytic fragments of Pmel17 form insoluble, amyloid-like fibrils upon which
      melanins are deposited during melanosome maturation. The mechanism(s) by which
      Pmel17 becomes competent to form amyloid are not fully understood. To better
      understand how amyloid formation is regulated, we have defined the domains within
      Pmel17 that promote fibril formation in vitro. Using purified recombinant
      fragments of Pmel17, we show that two regions, an N-terminal domain of unknown
      structure and a downstream domain with homology to a polycystic kidney disease-1
      repeat, efficiently form amyloid in vitro. Analyses of fibrils formed in
      melanocytes confirm that the polycystic kidney disease-1 domain forms at least
      part of the physiological amyloid core. Interestingly, this same domain is also
      required for the intracellular trafficking of Pmel17 to multivesicular
      compartments within which fibrils begin to form. Although a domain of imperfect
      repeats (RPT) is required for fibril formation in vivo and is a component of
      fibrils in melanosomes, RPT is not necessary for fibril formation in vitro and in
      isolation is unable to adopt an amyloid fold in a physiologically relevant time
      frame. These data define the structural core of Pmel17 amyloid, imply that the
      RPT domain plays a regulatory role in timing amyloid conversion, and suggest that
      fibril formation might be physically linked with multivesicular body sorting.

PMID- 19840946
TI  - PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3
      phosphatase activity and endocytic membrane homeostasis.
AB  - The phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P(2)) metabolizing enzymes,
      the kinase PIKfyve and the phosphatase Sac3, constitute a single multiprotein
      complex organized by the PIKfyve regulator ArPIKfyve and its ability to
      homodimerize. We previously established that PIKfyve is activated within the
      triple PIKfyve-ArPIKfyve-Sac3 (PAS) core. These data assign an atypical function
      for the phosphatase in PtdIns(3,5)P(2) biosynthesis, thus raising the question of
      whether Sac3 retains its PtdIns(3,5)P(2) hydrolyzing activity within the PAS
      complex. Herein, we address the issue of Sac3 functionality by a combination of
      biochemical and morphological assays in triple-transfected COS cells using a
      battery of truncated or point mutants of the three proteins. We identified the
      Cpn60_TCP1 domain of PIKfyve as a major determinant for associating the ArPIKfyve
      Sac3 subcomplex. Neither Sac3 nor PIKfyve enzymatic activities affected the PAS
      complex formation or stability. Using the well established formation of aberrant
      cell vacuoles as a sensitive functional measure of localized PtdIns(3,5)P(2)
      reduction, we observed a mitigated vacuolar phenotype by kinase-deficient
      PIKfyve(K1831E) if its ArPIKfyve-Sac3 binding region was deleted, suggesting
      reduced Sac3 access to, and turnover of PtdIns(3,5)P(2). In contrast,
      PIKfyve(K1831E), which displays intact ArPIKfyve-Sac3 binding, triggered a more
      severe vacuolar phenotype if coexpressed with ArPIKfyve(WT)-Sac3(WT) but minimal
      defects when coexpressed with ArPIKfyve(WT) and phosphatase-deficient
      Sac3(D488A). These data indicate that Sac3 assembled in the PAS regulatory core
      complex is an active PtdIns(3,5)P(2) phosphatase. Based on these and other data,
      presented herein, we propose a model of domain interactions within the PAS core
      and their role in regulating the enzymatic activities.

PMID- 19840947
TI  - Splicing factor arginine/serine-rich 17A (SFRS17A) is an A-kinase anchoring
      protein that targets protein kinase A to splicing factor compartments.
AB  - Protein kinase A (PKA) is targeted to distinct subcellular localizations by
      specific protein kinase A anchoring proteins (AKAPs). AKAPs are divided into
      subclasses based on their ability to bind type I or type II PKA or both. Dual
      specificity AKAPs were recently reported to have an additional PKA binding
      determinant called the RI specifier region. A bioinformatic search with the
      consensus RI specifier region identified a novel AKAP, the splicing factor
      arginine/serine-rich 17A (SFRS17A). Here, we show by a variety of protein
      interaction assays that SFRS17A binds both type I and type II PKA in vitro and
      inside cells, demonstrating that SFRS17A is a dual-specific AKAP. Moreover,
      immunofluorescence experiments show that SFRS17A colocalizes with the catalytic
      subunit of PKA as well as the splicing factor SC35 in splicing factor
      compartments. Using the E1A minigene splicing assay, we found that expression of
      wild type SFRS17A conferred regulation of E1A alternative splicing, whereas the
      mutant SFRS17A, which is unable to bind PKA, did not. Our data suggest that
      SFRS17A is an AKAP involved in regulation of pre-mRNA splicing possibly by
      docking a pool of PKA in splicing factor compartments.

PMID- 19840948
TI  - Purification of nuclear poly(A)-binding protein Nab2 reveals association with the
      yeast transcriptome and a messenger ribonucleoprotein core structure.
AB  - Nascent mRNAs produced by transcription in the nucleus are subsequently processed
      and packaged into mRNA ribonucleoprotein particles (messenger ribonucleoproteins
      (mRNPs)) before export to the cytoplasm. Here, we have used the poly(A)-binding
      protein Nab2 to isolate mRNPs from yeast under conditions that preserve mRNA
      integrity. Upon Nab2-tandem affinity purification, several mRNA export factors
      were co-enriched (Yra1, Mex67, THO-TREX) that were present in mRNPs of different
      size and mRNA length. High-throughput sequencing of the co-precipitated RNAs
      indicated that Nab2 is associated with the bulk of yeast transcripts with no
      specificity for different mRNA classes. Electron microscopy revealed that many of
      the mRNPs have a characteristic elongated structure. Our data suggest that mRNPs,
      although associated with different mRNAs, have a unifying core structure.

PMID- 19840949
TI  - A single UDP-galactofuranose transporter is required for galactofuranosylation in
      Aspergillus fumigatus.
AB  - Galactofuranose (Galf) containing molecules have been described at the cell
      surface of several eukaryotes and shown to contribute to the virulence of the
      parasite Leishmania major and the fungus Aspergillus fumigatus. It is anticipated
      that a number of the surface glycoconjugates such as N-glycans or glycolipids are
      galactofuranosylated in the Golgi apparatus. This raises the question of how the
      substrate for galactofuranosylation reactions, UDP-Galf, which is synthesized in
      the cytosol, translocates into the organelles of the secretory pathway. Here we
      report the first identification of a Golgi-localized nucleotide sugar
      transporter, named GlfB, with specificity for a UDP-Galf. In vitro transport
      assays established binding of UDP-Galf to GlfB and excluded transport of several
      other nucleotide sugars. Furthermore, the implication of glfB in the
      galactofuranosylation of A. fumigatus glycoconjugates and galactomannan was
      demonstrated by a targeted gene deletion approach. Our data reveal a direct
      connection between galactomannan and the organelles of the secretory pathway that
      strongly suggests that the cell wall-bound polysaccharide originates from its
      glycosylphosphatidylinositol-anchored form.

PMID- 19840950
TI  - Loss of myosin VI no insert isoform (NoI) induces a defect in clathrin-mediated
      endocytosis and leads to caveolar endocytosis of transferrin receptor.
AB  - Myosin VI is a motor protein that moves toward the minus end of actin filaments.
      It is involved in clathrin-mediated endocytosis and associates with clathrin
      coated pits/vesicles at the plasma membrane. In this article the effect of the
      loss of myosin VI no insert isoform (NoI) on endocytosis in nonpolarized cells
      was examined. The absence of myosin VI in fibroblasts derived from the Snell's
      waltzer mouse (myosin VI knock-out) gives rise to defective clathrin-mediated
      endocytosis with shallow clathrin-coated pits and a strong reduction in the
      internalization of clathrin-coated vesicles. To compensate for this defect in
      clathrin-mediated endocytosis, plasma membrane receptors such as the transferrin
      receptor (TfR) are internalized by a caveola-dependent pathway. Moreover the
      clathrin adaptor protein, AP-2, necessary for TfR internalization, follows the
      receptor and relocalizes in caveolae in Snell's waltzer fibroblasts.

PMID- 19840951
TI  - D-loop of actin differently regulates the motor function of myosins II and V.
AB  - To gain more information on the manner of actin-myosin interaction, we examined
      how the motile properties of myosins II and V are affected by the modifications
      of the DNase I binding loop (D-loop) of actin, performed in two different ways,
      namely, the proteolytic digestion with subtilisin and the M47A point mutation. In
      an in vitro motility assay, both modifications significantly decreased the
      gliding velocity on myosin II-heavy meromyosin due to a weaker generated force
      but increased it on myosin V. On the other hand, single molecules of myosin V
      "walked" with the same velocity on both the wild-type and modified actins;
      however, the run lengths decreased sharply, correlating with a lower affinity of
      myosin for actin due to the D-loop modifications. The difference between the
      single-molecule and the ensemble measurements with myosin V indicates that in an
      in vitro motility assay the non-coordinated multiple myosin V molecules impose
      internal friction on each other via binding to the same actin filament, which is
      reduced by the weaker binding to the modified actins. These results show that the
      D-loop strongly modulates the force generation by myosin II and the processivity
      of myosin V, presumably affecting actin-myosin interaction in the actomyosin
      ADP.P(i) state of both myosins.

PMID- 19840952
TI  - Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth
      muscle cells via epidermal growth factor receptor signalling.
AB  - AIMS: Fractalkine (CX3CL1) is a membrane-bound chemokine that signals through the
      G protein-coupled receptor CX3CR1 that is implicated in the development of
      atherosclerosis. We have previously reported that CX3CR1 is expressed by primary
      human coronary artery smooth muscle cells (CASMC), where it mediates chemotaxis
      towards CX3CL1. We sought to determine the effect of CX3CL1 on CASMC survival and
      proliferation and elucidate the signalling mechanisms involved. METHODS AND
      RESULTS: CX3CL1 significantly reduces staurosporine-induced apoptosis of CASMC,
      as quantified by caspase 3 immunostaining and Annexin-V flow cytometry.
      Furthermore, CX3CL1 is a potent mitogen for primary CASMC and induces
      phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, measured
      by western blotting. Inhibition of either ERK or phosphoinositide 3-kinase (PI3K)
      signalling abrogates proliferation, while only PI3K signalling is involved in the
      anti-apoptotic effects of CX3CL1. We describe a novel and specific small molecule
      antagonist of CX3CR1 (AZ12201182) which abrogates the mitogenic and anti
      apoptotic effects of CX3CL1 on CASMC. Pharmacological inhibition of the epidermal
      growth factor receptor (EGFR) blocks CASMC survival and DNA synthesis, indicating
      a previously undocumented role for EGFR signalling in response to CX3CL1
      involving release of a soluble EGFR ligand. Specifically, CX3CL1 induces shedding
      of epiregulin and increases epiregulin mRNA expression 20-fold within 2 h.
      Finally, antibody neutralization of epiregulin abrogates the mitogenic effect of
      CX3CL1. CONCLUSION: We have demonstrated two novel and important functions of
      CX3CL1 on primary human SMCs: anti-apoptosis and proliferation, both mediated via
      epiregulin-induced EGFR signalling. Our data have important implications in
      vascular pathologies including atherosclerosis, restenosis, and transplant
      accelerated arteriosclerosis, where the balance of SMC proliferation and
      apoptosis critically determines both plaque stability and vessel stenosis.

PMID- 19840953
TI  - Breast cancer brain metastases: differences in survival depending on biological
      subtype, RPA RTOG prognostic class and systemic treatment after whole-brain
      radiotherapy (WBRT).
AB  - BACKGROUND: Patients with breast cancer brain metastasis are a heterogeneous
      group in relation to tumor biology and outcome. MATERIALS AND METHODS: The group
      of 222 breast cancer patients with brain metastasis was divided into three
      biological subgroups. The propensity of biological subtypes for metastases to the
      brain and survivals depending on biological subtype, recursive partitioning
      analysis of Radiation Therapy Oncology Group (RPA RTOG) prognostic class and the
      use of systemic treatment after whole-brain radiotherapy were assessed. RESULTS:
      The rate of patients with triple-negative, human epidermal growth factor receptor
      2 (HER2)-positive and luminal breast cancer with brain metastases was 28%, 53%
      and 19%, respectively. Median survival from brain metastases in triple-negative,
      HER2-positive and luminal subtype was 3.7, 9 and 15 months, respectively. Median
      survival from brain metastases in RPA RTOG prognostic class I, II and III was 15,
      11 and 3 months, respectively. In the luminal and in the triple-negative subtype,
      systemic therapy prolonged survival from 3 to 14 months and from 3 to 4 months,
      respectively. In HER2-positive subtype, median survival without further
      treatment, after chemotherapy and after chemotherapy with targeted therapy were
      3, 8 and 11 months, respectively. CONCLUSIONS: HER2-positive and triple-negative
      breast cancers have special predilection for metastases to the brain. Survival
      from brain metastases depended on performance status and the use of systemic
      treatment.

PMID- 19840954
TI  - House dust mite induces direct airway inflammation in vivo: implications for
      future disease therapy?
AB  - House dust mite (HDM) is the major source of allergen in house dust and is
      strongly associated with the development of asthma. HDM can evoke a direct,
      nonallergic inflammatory reaction in vitro. We aimed to determine whether this
      apparent nonallergic, inflammatory response can be observed in a more complex in
      vivo setting. Vehicle, Alum or HDM (Dermatophagoides pteronyssinus 5 microg, i.p.
      with Alum) sensitised Brown-Norway rats were challenged intratracheally with
      vehicle (saline), HDM (Der p 10 microg) or heat-inactivated HDM on day 21. Lung
      function changes and the associated inflammatory response were evaluated. Tissue
      and bronchoalveolar lavage from Alum sensitised Der p challenged animals
      exhibited strong eosinophilia and neutrophilia associated with an early release
      of pro-inflammatory cytokines (interleukin-13 and 1beta, eotaxin and thymus and
      activation-regulated chemokine). This response was not attenuated by removal of
      HDM-associated protease activity. Interestingly, the vehicle sensitised group (no
      Alum) lacked this inflammatory response. HDM allergen evokes nonallergic airways
      inflammation with an inflammatory profile similar to that of the asthmatic
      airway. This response, independent of the protease activity of the HDM extract,
      appeared to be linked to prior administration of the adjuvant Alum and the
      subsequent increase in total immunoglobulin E. This finding could have important
      implications in the development of future asthma therapies.

PMID- 19840955
TI  - Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial
      cells.
AB  - alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which
      manifests as early-onset emphysema or liver disease. Although the majority of
      alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial
      cells, amongst others, in the lung. Herein, we investigate the effects of mutant
      Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell
      line (16HBE14o-) and delineate the mechanisms involved. Control, M variant
      alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase
      3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB
      activation and induced expression of a selection of pro- and anti-apoptotic
      genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and
      agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by
      57% compared with control cells (p = 0.05) and was a more potent inhibitor than
      MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated
      NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In
      16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an
      upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus
      MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may
      promote human bronchial epithelial cell survival.

PMID- 19840956
TI  - No evidence for interstitial lung oedema by extensive pulmonary function testing
      at 4,559 m.
AB  - The aim of the present study was to better understand previously reported changes
      in lung function at high altitude. Comprehensive pulmonary function testing
      utilising body plethysmography and assessment of changes in closing volume were
      carried out at sea level and repeatedly over 2 days at high altitude (4,559 m) in
      34 mountaineers. In subjects without high-altitude pulmonary oedema (HAPE), there
      was no significant difference in total lung capacity, forced vital capacity,
      closing volume and lung compliance between low and high altitude, whereas lung
      diffusing capacity for carbon monoxide increased at high altitude.
      Bronchoconstriction at high altitude could be excluded as the cause of changes in
      closing volume because there was no difference in airway resistance and
      bronchodilator responsiveness to salbutamol. There were no significant
      differences in these parameters between mountaineers with and without acute
      mountain sickness. Mild alveolar oedema on radiographs in HAPE was associated
      only with minor decreases in forced vital capacity, diffusing capacity and lung
      compliance and minor increases in closing volume. Comprehensive lung function
      testing provided no evidence of interstitial pulmonary oedema in mountaineers
      without HAPE during the first 2 days at 4,559 m. Data obtained in mountaineers
      with early mild HAPE suggest that these methods may not be sensitive enough for
      the detection of interstitial pulmonary fluid accumulation.

PMID- 19840957
TI  - Marginal decline in forced vital capacity is associated with a poor outcome in
      idiopathic pulmonary fibrosis.
AB  - In therapeutic studies in idiopathic pulmonary fibrosis (IPF), the low prevalence
      of significant change in pulmonary functional tests (PFTs) has been a major
      constraint. The prognostic value of "marginal" changes in PFTs in IPF and
      fibrotic non-specific interstitial pneumonia (NSIP) was evaluated. In patients
      with biopsy-proven IPF (n = 84) and NSIP (n = 72), forced vital capacity (FVC)
      and diffusing capacity of the lung for carbon monoxide (D( L,CO)) trends at 6
      months were categorised as "significant" (FVC >10%; D(L,CO) >15%) or "marginal"
      (FVC 5-10%; D(L,CO) 7.5-15%). Proportional hazards analysis and time-dependent
      receiver operating characteristic methodology were used to examine PFT trends
      against mortality. In IPF, reductions in FVC were significant in 22 cases (26%)
      and marginal in 19 cases (23%). Mortality was higher in patients with a
      significant decline in FVC (hazard ratio (HR) 2.80, 95% CI 1.54-5.06; p<0.001)
      and those with a marginal decline in FVC (HR 2.31, 95% CI 1.19-4.50; p = 0.01)
      than in those with stable disease. Progression-free survival was lower when the
      decline in FVC was marginal than in stable disease (HR 2.34, 95% CI 1.19-4.60; p
      = 0.01). Marginal changes in D(L,CO) in IPF and marginal changes in FVC and D
      (L,CO) in fibrotic NSIP did not provide useful prognostic information. Marginal
      change in FVC in IPF denotes a poor outcome. These findings are applicable to
      clinical practice and to the selection of patients with more progressive disease
      for therapeutic studies.

PMID- 19840958
TI  - Respiratory medicines for children: current evidence, unlicensed use and research
      priorities.
AB  - This European Respiratory Society task force has reviewed the evidence for
      paediatric medicines in respiratory disease occurring in adults and children. We
      describe off-licence use, research priorities and ongoing studies. Off-licence
      and off-label prescribing in children is widespread and potentially harmful.
      Research areas in asthma include novel formulations and regimens, and
      individualised prescribing. In cystic fibrosis, future studies will focus on
      screened infants and robust outcome measures are needed. Other areas include new
      enzyme and antibiotic formulations and the basic defect. Research into pneumonia
      should include evaluation of new antibacterials and regimens, rapid diagnostic
      tests and, in pleural infection, antibiotic penetration, fibrinolytics and
      surveillance. In uncommon conditions, such as primary ciliary dyskinesia,
      congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated
      for other conditions (e.g. dornase alfa) are commonly used and trials are needed.
      In neuromuscular disorders, the beta-agonists may enhance muscle strength and are
      in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and
      antifungal drugs are needed in immune deficiency. We hope that this summary of
      the evidence for respiratory medicines in children, highlighting gaps and
      research priorities, will be useful for the pharmaceutical industry, the
      paediatric committee of the European Medicines Agency, academic investigators and
      the lay public.

PMID- 19840959
TI  - Cigarette smoke modulates rhinovirus-induced airway epithelial cell chemokine
      production.
AB  - Human rhinovirus (HRV) infections induce epithelial cell production of chemokines
      that may contribute to the pathogenesis of exacerbations of chronic obstructive
      pulmonary disease (COPD) and asthma. Cigarette smoking is the predominant risk
      factor for the development of COPD and also aggravates asthma symptoms. We
      examined whether cigarette smoke extract (CSE) modulates viral inflammation by
      altering the profile of HRV-induced epithelial chemokine production. Purified HRV
      16, and CSE were used to examine the effects on CXC chemokine ligand (CXCL)8 and
      CXCL10 production from both primary human bronchial epithelial cells and the BEAS
      2B epithelial cell line. Both CSE and HRV-16 induced CXCL8 production and, when
      used in combination, induced at least an additive production of CXCL8 compared
      with either stimulus alone. In contrast, CSE did not induce CXCL10 and markedly
      inhibited HRV-16-induced CXCL10 production. Inhibition of HRV-16-induced CXCL10
      by CSE was mediated, at least in part, via transcriptional regulation. The
      increased CXCL8 production seen with the combination of CSE and HRV-16 was not
      due to transcriptional regulation but was associated with CXCL8 mRNA
      stabilisation. Thus, CSE differentially modulates HRV-16-induced chemokine
      production from human airway epithelial cells in a manner that might be expected
      to alter inflammatory cell profiles.

PMID- 19840960
TI  - Optimal positive airway pressure predicts oral appliance response to sleep
      apnoea.
AB  - Patients with less severe obstructive sleep apnoea (OSA) are usually prescribed
      oral appliances and/or smaller optimal nasal continuous positive airway pressure
      (P(nCPAP)) in nCPAP therapy. We hypothesised that OSA patients with greater
      P(nCPAP) would not respond favourably to oral appliances. Oral appliances were
      inserted in nCPAP users after washing-out the nCPAP effect. Follow-up
      polysomnography was undertaken with the adjusted oral appliance in place. The
      predictability of P(nCPAP) was evaluated with receiver-operating characteristic
      (ROC) curves. The median baseline apnoea/hypopnoea index (AHI) was reduced with
      the oral appliance from 36 to 12 events.h(-1) in 35 patients. When responders
      were defined as patients showing a follow-up AHI of <5 events.h(-1) with >50%
      reduction in baseline AHI, the area under the ROC curve for P(nCPAP) was 0.76.
      The best cut-off value of P(nCPAP) turned out to be 10.5 cmH(2)O with a high
      negative predictive value (0.93) and a low negative likelihood ratio (0.18). OSA
      patients with a P(nCPAP) of >10.5 cmH( 2)O are unlikely to respond to oral
      appliance therapy. This prediction is clinically helpful to both OSA patients and
      medical personnel in discussing oral appliances as a temporary substitute and/or
      alternative for nCPAP.

PMID- 19840961
TI  - A model of chronic lung allograft rejection in the rat.
AB  - Bronchiolitis obliterans, the pathological hallmark of chronic pulmonary
      rejection, severely impacts long-term survival following lung transplantation.
      However, experimental reproduction of this pathophysiological phenomenon has not
      been achieved with contemporary in vivo models. Here, a model of chronic
      rejection is described, with sensitised recipients receiving unilateral
      orthotopic rat lung transplants. Lewis rats, sensitised with skin from brown
      Norway rats 7 days before receiving left lung transplants from donors that were
      Lewis x brown Norway F(1) hybrids, were analysed during day 21-84. The
      development of chronic rejection was modulated by a treatment with rapamycin and
      cyclosporin, and characterised histologically, immunohistochemically and by
      reverse transcriptase PCR. Characteristic histopathological changes leading to
      chronic rejection were induced over time by an initial treatment with cyclosporin
      in the presence of continuous rapamycin application. At day 84, fibrotic lesions
      replaced the respiratory epithelium within small bronchioles, with strong
      expression of smooth muscle alpha-actin and upregulation of mRNA for T-helper
      cell type-1 cytokines, smooth muscle alpha-actin, transforming growth factor-beta
      and CC chemokine ligand 5, but decreased forkhead box protein P3 gene expression.
      A reproducible and clinically relevant experimental set-up for progressive
      chronic rejection in rat pulmonary allografts is described. This model will
      permit better understanding of the pathological changes of small airways during
      the development of bronchiolitis obliterans, and may serve as an in vivo set-up
      for testing the efficacy of novel therapeutic interventions.

PMID- 19840962
TI  - Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in
      infants.
AB  - The present prospective study examined the association between maternal
      consumption of dairy products, calcium, and vitamin D during pregnancy and the
      risk of wheeze and eczema in the infants aged 16-24 months. Subjects were 763
      Japanese mother-child pairs. Data on maternal intake during pregnancy were
      assessed with a diet history questionnaire. Symptoms of wheeze and eczema were
      based on criteria of the International Study of Asthma and Allergies in
      Childhood. Higher maternal intake of total dairy products, milk, cheese and
      calcium during pregnancy was significantly related to a decreased risk of
      infantile wheeze, but not eczema (adjusted ORs (95% CI) between extreme quartiles
      were 0.45 (0.25-0.79), 0.50 (0.28-0.87), 0.51 (0.31-0.85), and 0.57 (0.32-0.99),
      respectively). When maternal vitamin D consumption during pregnancy was
      categorised into two groups using a cut-off point at the 25th percentile,
      children whose mothers had consumed > or =4.309 microg x day(-1) had a
      significantly reduced risk of wheeze and eczema (adjusted ORs (95% CI) were 0.64
      (0.43-0.97) and 0.63 (0.41-0.98), respectively). Higher consumption of calcium
      and dairy foods other than yoghurt during pregnancy may reduce the risk of
      infantile wheeze. Higher vitamin D intake during pregnancy may be protective
      against childhood wheeze and eczema.

PMID- 19840963
TI  - Predictive value for progression to tuberculosis by IGRA and TST in immigrant
      contacts.
AB  - The authors determined the positive predictive value (PPV) for progression to
      tuberculosis (TB) of two interferon-gamma release assays (IGRAs), QuantiFERON-TB
      Gold In-tube (QFT-GIT) and T-SPOT.TB, and the tuberculin skin test (TST) in
      immigrants contacts. Immigrant close contacts of sputum smear-positive TB
      patients were included when aged > or =16 yrs and their TST result was > or =5 mm
      0 or 3 months after diagnosis of the index patient. Contacts were followed for
      the next 2 yrs for development of TB disease. Of 339 immigrant contacts with TST
      > or =5 mm, 324 and 299 had valid results of QFT-GIT and T-SPOT.TB, respectively.
      Nine contacts developed active TB. One patient had not been tested with TST,
      while another patient had not been tested with QFT-GIT and T-SPOT.TB. The PPV for
      progression to TB during this period was 9/288 = 3.1% (95% CI 1.3-5.0%) for TST >
      or =10 mm, 7/184 = 3.8% (95% CI 1.7-5.9%) for TST > or =15 mm, 5/178 = 2.8% (95%
      CI 1.0-4.6%) for QFT-GIT and 6/181 = 3.3% (95% CI 1.3-5.3%) for T-SPOT.TB.
      Sensitivity was 100%, 88%, 63% and 75%, respectively. The predictive values of
      QFT-GIT, T-SPOT.TB and TST for progression to TB disease among immigrant close
      contacts were comparable.

PMID- 19840964
TI  - Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species
      generation.
AB  - Previous studies have identified abnormalities in the oxidative responses of the
      neutrophil in cystic fibrosis (CF), but it is unclear whether such changes relate
      to loss of membrane cystic fibrosis transmembrane conductance regulator (CFTR) or
      to the inflammatory environment present in this disease. The aim of the present
      study was to determine whether neutrophils from CF patients demonstrate an
      intrinsic abnormality of the respiratory burst. The respiratory burst activity of
      neutrophils isolated from stable DeltaF508 homozygote CF patients and matched
      healthy controls was quantified by both chemiluminscence and cytochrome C
      reduction. Expression of NADPH oxidase components and CFTR was determined by
      Western blotting and RT-PCR. The oxidative output from neutrophils from CF in
      response to receptor-linked and particulate stimuli did not differ from that of
      controls. Expression of NADPH oxidase components was identical in CF and non-CF
      neutrophils. While low levels of CFTR mRNA could be identified in the normal
      human neutrophil, we were unable to detect CFTR protein in human neutrophil
      lysates or immunoprecipitates. CFTR has no role in controlling neutrophil
      oxidative activity; previously reported differences in neutrophil function
      between CF and non-CF subjects most likely relate to the inflammatory milieu from
      which the cells were isolated.

PMID- 19840965
TI  - Diffuse alveolar haemorrhage: factors associated with in-hospital and long-term
      mortality.
AB  - Diffuse alveolar haemorrhage (DAH) is a feature of several immune and nonimmune
      disorders. Reported prognosis is poor, with in-hospital mortality ranging from
      20% to 100%. Early identification of prognostic factors may be useful in the
      initiation of appropriate treatment. We retrospectively analysed the charts of
      all patients referred to a university hospital for DAH between 1980 and 2008.
      Variables associated with in-hospital and long-term mortality were determined
      using a logistic regression model and the Kaplan-Meier method, respectively.
      Immunosuppressed patients were excluded. Overall, 97 patients were included in
      the study. In-hospital mortality was 24.7%. Factors associated with in-hospital
      mortality were shock (OR 77.5, 95% CI 8.9-677.2), glomerular filtration rate <60
      mL x min(-1) (OR 11.2, 95% CI 1.8-68.4) and plasmatic lactate dehydrogenase level
      more than twice the normal value (OR 12.1, 95% CI 1.7-84.3). Mortality among
      discharged patients was 16.4% with a median follow-up duration of 34 months.
      Factors associated with increased long-term mortality in univariate analysis were
      age over 60 yrs (p = 0.026), cardiovascular comorbidity (p = 0.027) and end-stage
      renal failure with dependence on haemodialysis (p = 0.026). Patients with immune
      and nonimmune DAH had similar outcomes. Early outcome depended on nonpulmonary
      organ failures. Conversely, late outcome was related to age, cardiac
      comorbidities and the need for haemodialysis.

PMID- 19840966
TI  - Alveolar fibroblasts in acute lung injury: biological behaviour and clinical
      relevance.
AB  - Although fibroblasts are key cells in the lung repair/fibrosis process, their
      characteristics are poorly studied in acute lung injury (ALI) and acute
      respiratory distress syndrome (ARDS). The aims of our study were to: 1) determine
      the biological behaviour of alveolar fibroblasts during ALI; and 2) to evaluate
      the clinical relevance of positive alveolar fibroblast culture from patients with
      ALI/ARDS. Cells were cultured from bronchoalveolar lavage (BAL) obtained from 68
      critically ill, ventilated patients: ALI n = 17; ARDS n = 31; and ventilated
      controls n = 20. Patients were followed for 28 days and clinical data was
      recorded. We studied proliferation, migration and collagen-1 synthesis capacities
      of fibroblasts. Cells expressing fibroblast markers were cultured from BAL
      obtained in six (35%) ALI patients and six (19%) ARDS patients, but never from
      ventilated controls. Alveolar fibroblasts exhibited a persistent activated
      phenotype with enhanced migratory and collagen-1 production capacities, with
      hyporesponsiveness to prostaglandin E(2) compared to normal lung fibroblasts (p<
      or =0.04). Positive fibroblast culture was associated with both an increased
      collagen-1 concentration and monocyte/macrophage percentage in BAL fluid (p< or
      =0.01), and with a reduced duration of mechanical ventilation (p<0.001). We
      conclude that activated alveolar fibroblasts can be cultured either in ALI or
      ARDS and that their presence might reflect the initiation of the organising phase
      of ALI.

PMID- 19840967
TI  - Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release
      in severe asthma.
AB  - Patients with severe asthma respond less well to corticosteroids than those with
      non-severe asthma. Increased p38 mitogen-activated protein kinase (MAPK)
      activation in alveolar macrophages (AMs) from severe asthma patients has been
      associated with a reduced inhibition of cytokine release by dexamethasone. We
      determined whether p38 MAPK inhibitors would modulate corticosteroid suppression
      of cytokine release from AMs and peripheral blood mononuclear cells (PBMCs).
      PBMCs were isolated from venous blood and AMs by bronchoalveolar lavage in severe
      and non-severe asthma patients. PBMCs and AMs were exposed to lipopolysaccharide
      (LPS) with and without the p38 MAPK inhibitor, SD282, or dexamethasone. We
      determined the concentration-dependent effects of another p38 MAPK inhibitor, GW
      A, on dexamethasone-induced inhibition of interleukin (IL)-8 release from PBMCs.
      Cytokines were assayed using an ELISA-based method. SD282 (10(-7) M), with
      dexamethasone (10( -6) M), caused a greater inhibition of release of IL-1beta, IL
      6, macrophage inflammatory protein-1alpha and IL-10, than with dexamethasone
      alone in AMs from severe and non-severe asthma. At 10(-9) and 10(-10) M, GW-A,
      that had no direct effects, increased the inhibitory activity of dexamethasone
      (10(-8) and 10( -6) M) on LPS-induced IL-8 release in PBMCs from severe asthma.
      Corticosteroid insensitivity in severe asthma patients may be improved by
      inhibitors of p38 MAPK.

PMID- 19840968
TI  - Cigarette smoke induces CXCL8 production by human neutrophils via activation of
      TLR9 receptor.
AB  - Chronic obstructive pulmonary disease (COPD) is a major health problem and
      cigarette smoke is the main risk factor for the development of COPD. The
      characteristic changes in airway morphology, inflammatory cell infiltration and
      mediator expression in COPD may result from direct effects of cigarette smoke on
      airway cells. Toll-like receptors (TLRs) are key elements in pathogen recognition
      by the host immune system. Although TLRs have been intensely studied in innate
      immunity and infection, their critical role in noninfectious challenges has only
      recently emerged. Here we investigate whether cigarette smoke induces TLR9
      signalling in human neutrophils. Human neutrophils were isolated from buffy coat
      and exposed to cigarette smoke extract. The production of CXC chemokine ligand
      (CXCL)8 was measured as a functional readout and the role of TLR9 signalling was
      investigated. Cigarette smoke extract induced CXCL8 release via TLR9 activation
      in neutrophils, which was confirmed in TLR9 stably transfected human embryonic
      kidney 293 cells. Moreover, cigarette smoke extract upregulated the expression of
      TLR9 and the upregulated expression was suppressed by N-acetylcysteine. TLR9
      mediates cigarette smoke-induced release of CXCL8 and this may contribute to the
      accumulation of neutrophils and inflammation within the airways of smokers.

PMID- 19840969
TI  - Profiling hospital performance to monitor the quality of care: the case of COPD.
AB  - Comparative outcomes data are widely used to monitor quality of care in the
      cardiovascular area; little is available in the respiratory field. We applied
      validated methods to compare hospital outcomes for chronic obstructive pulmonary
      disease (COPD) exacerbation. From the hospital information system, we selected
      all hospital admissions for COPD exacerbation in Rome (for 2001-2005). Vital
      status within 30 days was obtained from the municipality mortality register. Each
      hospital was compared to a pool of hospitals with the lowest adjusted mortality
      rate (the benchmark). Age, sex and several potential clinical predictors were
      covariates in logistic regression analysis. 12,756 exacerbated COPD patients were
      analysed (mean age 74 yrs, 71% males). Diabetes, hypertension, ischaemic heart
      disease, heart failure and arrhythmia were the most common coexisting conditions.
      The average crude mortality in the benchmark group was 3.8%; in the remaining
      population it was 7.5% (range 5.2-17.2%). In comparison with the benchmark, the
      relative risk of 30-day mortality varied widely across the hospitals (range 1.5
      5.9%). A large variability in 30-day mortality after COPD exacerbation exists
      even considering patients' characteristics. Although these results do not detect
      mechanisms related to worse outcomes, they may be useful to stimulate providers
      to revision and improvement of COPD care management.

PMID- 19840970
TI  - Active screening at entry for tuberculosis among new immigrants: a systematic
      review and meta-analysis.
AB  - Although there is no evidence that imported tuberculosis increases the incidence
      of the disease in host countries, the rise in migration worldwide raises concerns
      regarding the adequacy of surveillance and control of immigrant-associated
      tuberculosis in low incidence countries. Assessing the performance of screening
      of immigrants for tuberculosis is key to rationalizing control policies for the
      detection and management of immigrant-associated tuberculosis. We performed a
      systematic review and meta-analysis to determine the yield of active screening
      for tuberculosis among new immigrants at the point of entry. The yield for
      pulmonary tuberculosis was 3.5 cases per 1,000 screened (95% CI 2.9-4.1; I(2) =
      94%); for refugees, asylum seekers and regular immigrants the estimates were 11.9
      (95% CI 6.7-17.2; I(2) = 92%), 2.8 (95% CI 2.0-3.7; I(2) = 96%) and 2.7 (95% CI
      2.0-3.4; I(2) = 81%), respectively. The yield estimates for immigrants from
      Europe, Africa and Asia were 2.4 (95% CI 1.3-3.4; I(2) = 51.5%), 6.5 (95% CI 3.2
      10.0; I(2) = 62%) and 11.2 (95% CI 6.2-16.1; I(2) = 95%), respectively. These
      results provide useful data to inform the development of coherent policies and
      rational screening services for the detection of immigrant-associated
      tuberculosis.

PMID- 19840971
TI  - A 20-year experience of electron microscopy in the diagnosis of primary ciliary
      dyskinesia.
AB  - Transmission electron microscopy (TEM) analysis of ciliary ultrastructure is
      classically used for the diagnosis of primary ciliary dyskinesia (PCD). We report
      our extensive experience of TEM analysis in a large series of patients in order
      to evaluate its feasibility and results. TEM analysis performed in 1,149 patients
      with suspected PCD was retrospectively reviewed. Biopsies (1,450) were obtained
      from nasal (44%) or bronchial (56%) mucosa in children (66.5%) and adults
      (33.5%). TEM analysis was feasible in 71.4% of patients and showed a main defect
      suggestive of PCD in 29.9%. TEM was more feasible in adults than in children,
      regardless of the biopsy site. Main defects suggestive of PCD were found in 76.9%
      of patients with sinopulmonary symptoms and in only 0.4% of patients with
      isolated upper and 0.4% with isolated lower respiratory tract infections. The
      defect pattern was similar in children and adults, involving dynein arms (81.2%)
      or central complex (CC) (18.8%). Situs inversus was never observed in PCD
      patients with CC defect. Kartagener syndrome with normal ciliary ultrastructure
      was not an exceptional condition (10.2% of PCD). In conclusion, TEM analysis is
      feasible in most patients and is particularly useful for PCD diagnosis in cases
      of sinopulmonary syndrome of unknown origin.

PMID- 19840972
TI  - Abdominal volume contribution to tidal volume as an early indicator of
      respiratory impairment in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is characterised by progressive loss of
      muscular strength that leads to an increasingly restrictive pulmonary syndrome.
      However, it is still not clear whether this determines alterations in the
      breathing pattern. We studied: 66 DMD patients at different stages of the disease
      (mean+/- sem age 12.6+/-0.6 yrs, range 5-22 yrs of age), subdivided into four
      groups according to age; and 21 age-matched healthy male controls. Spirometry,
      lung volumes and nocturnal oxygen saturation were measured in all DMD patients.
      Ventilatory pattern and chest wall volume variations were assessed by
      optoelectronic plethysmography during spontaneous breathing both in seated and
      supine positions. Whilst in a seated position, no significant differences were
      found between patients and controls or between different age groups. In the
      supine position, the average contribution of abdominal volume change (DeltaV(AB))
      to tidal volume progressively decreased with age (p<0.001). The patients who
      showed nocturnal hypoxaemia showed significantly lower Delta V(AB). In
      conclusion, chest wall motion during spontaneous breathing in awake conditions
      and in supine position is an important indicator of the degree of respiratory
      muscle impairment in DMD. DeltaV(AB) is not only an important marker of the
      progression of the disease but is also an early indicator of nocturnal
      hypoxaemia.

PMID- 19840973
TI  - Relation between corset use and lung function postural variation in spinal cord
      injury.
AB  - Corsets are widely used to improve trunk stability in patients with spinal cord
      injury (SCI) and can improve respiratory function. The aim of the present study
      was to identify predictors of respiratory benefits from wearing a corset in SCI
      patients. In a prospective observational study, respiratory function was tested
      in the supine and upright seated position with and without a corset in 36 SCI
      patients who regularly used a corset. SCI patients who no longer used a corset
      were matched to users on sex, injury level and severity. Vital capacity (VC) did
      not differ between users and nonusers in the supine position. In users, contrary
      to nonusers, VC increased significantly in the supine position compared to the
      seated position (increase of 0.43+/-0.39 versus -0.05+/-0.32 L in nonusers;
      p<0.0001). Corset use was associated with a significant VC increase in the
      upright position (2.13+/-0.71 L without versus 2.41+/-0.69 L with the corset;
      p<0.001). The VC increase with the corset in the upright position correlated
      significantly with the VC increase induced by being supine, compared to sitting
      without the corset. The VC increase induced in SCI patients by lying supine may
      predict the effects of wearing a corset. The long-term effects of corset use
      should be evaluated.

PMID- 19840974
TI  - The importance of failure: feedback-related negativity predicts motor learning
      efficiency.
AB  - Learning from past mistakes is of prominent importance for successful future
      behavior. In the present study, we tested whether reinforcement learning signals
      in the brain are predictive of adequate learning of a sequence of motor actions.
      We recorded event-related potentials (ERPs) while subjects engaged in a sequence
      learning task. The results showed that brain responses to feedback (the feedback
      related negativity [FRN]) predicted whether subjects learned to avoid an
      erroneous response the next time this action had to be performed. Our findings
      add to a growing literature on feedback-based performance adjustment, by showing
      that FRN amplitudes may reflect the acquisition of motor skill and the
      consolidation of contingencies between stimuli or cues and their associated
      responses, providing evidence that learning efficiency and future performance can
      be predicted by the neural response to current feedback: FRN amplitude associated
      with a mistake is predictive of whether this mistake will be repeated, or learned
      from.

PMID- 19840975
TI  - Influence of bisphosphonates on orthodontic tooth movement in mice.
AB  - Mechanical stress such as orthodontic tooth movement induces osteoclastogenesis.
      Sometimes, excessive mechanical stress results in root resorption during
      orthodontic tooth movement. It has been reported that bisphosphonate inhibits
      osteoclastogenesis. Recently, there have been concerns for orthodontic patients
      receiving bisphosphonates. Thus, the aim of this study was to investigate the
      effect of bisphosphonates on orthodontic tooth movement and root resorption in
      mice. A nickel-titanium (Ni-Ti) closed coil spring delivering a force of 10 g was
      inserted between the upper anterior alveolar bone and the first molar in 8-week
      old male C57BL/6 mice. Bisphosphonate (2 microg/20 microl) was injected daily
      into a local site adjacent to the upper molar. After 12 days, the distance the
      tooth had moved was measured. The number of tartrate-resistant acid phosphatase
      (TRAP)-positive cells was counted as osteoclasts in histological sections. Root
      resorption was assessed by scanning electron microscopy. The data were analysed
      with a Student's t-test. The orthodontic appliance increased the number of
      osteoclasts on the pressure side and mesial movement of the first molar.
      Bisphosphonates reduced the amount of tooth movement and the number of
      osteoclasts. In addition, they also reduced root resorption on the pressure side.
      Bisphosphonates inhibit orthodontic tooth movement and prevent root resorption
      during orthodontic tooth movement in mice. These results suggest that
      bisphosphonates might have an inhibiting effect on root resorption during
      orthodontic tooth movement in humans and that they may interrupt tooth movement
      in orthodontic patients undergoing treatment, thus altering the outcome of
      treatment.

PMID- 19840976
TI  - Mesh generation and mesh adaptation for large-scale Earth-system modelling.

PMID- 19840977
TI  - Logically rectangular finite volume methods with adaptive refinement on the
      sphere.
AB  - The logically rectangular finite volume grids for two-dimensional partial
      differential equations on a sphere and for three-dimensional problems in a
      spherical shell introduced recently have nearly uniform cell size, avoiding
      severe Courant number restrictions. We present recent results with adaptive mesh
      refinement using the GeoClaw software and demonstrate well-balanced methods that
      exactly maintain equilibrium solutions, such as shallow water equations for an
      ocean at rest over arbitrary bathymetry.

PMID- 19840978
TI  - Block-structured adaptive meshes and reduced grids for atmospheric general
      circulation models.
AB  - Adaptive mesh refinement techniques offer a flexible framework for future
      variable-resolution climate and weather models since they can focus their
      computational mesh on certain geographical areas or atmospheric events. Adaptive
      meshes can also be used to coarsen a latitude-longitude grid in polar regions.
      This allows for the so-called reduced grid setups. A spherical, block-structured
      adaptive grid technique is applied to the Lin-Rood finite-volume dynamical core
      for weather and climate research. This hydrostatic dynamics package is based on a
      conservative and monotonic finite-volume discretization in flux form with
      vertically floating Lagrangian layers. The adaptive dynamical core is built upon
      a flexible latitude-longitude computational grid and tested in two- and three
      dimensional model configurations. The discussion is focused on static mesh
      adaptations and reduced grids. The two-dimensional shallow water setup serves as
      an ideal testbed and allows the use of shallow water test cases like the
      advection of a cosine bell, moving vortices, a steady-state flow, the Rossby
      Haurwitz wave or cross-polar flows. It is shown that reduced grid configurations
      are viable candidates for pure advection applications but should be used
      moderately in nonlinear simulations. In addition, static grid adaptations can be
      successfully used to resolve three-dimensional baroclinic waves in the storm
      track region.

PMID- 19840979
TI  - Predicting mesh density for adaptive modelling of the global atmosphere.
AB  - The shallow water equations are solved using a mesh of polygons on the sphere,
      which adapts infrequently to the predicted future solution. Infrequent mesh
      adaptation reduces the cost of adaptation and load-balancing and will thus allow
      for more accurate mapping on adaptation. We simulate the growth of a
      barotropically unstable jet adapting the mesh every 12 h. Using an adaptation
      criterion based largely on the gradient of the vorticity leads to a mesh with
      around 20 per cent of the cells of a uniform mesh that gives equivalent results.
      This is a similar proportion to previous studies of the same test case with mesh
      adaptation every 1-20 min. The prediction of the mesh density involves solving
      the shallow water equations on a coarse mesh in advance of the locally refined
      mesh in order to estimate where features requiring higher resolution will grow,
      decay or move to. The adaptation criterion consists of two parts: that resolved
      on the coarse mesh, and that which is not resolved and so is passively advected
      on the coarse mesh. This combination leads to a balance between resolving
      features controlled by the large-scale dynamics and maintaining fine-scale
      features.

PMID- 19840980
TI  - An all-speed projection and filtering method for gravity-stratified flows.
AB  - Gravity waves arise in gravitationally stratified compressible flows at low Mach
      and Froude numbers, and these waves impose a sharp restriction on the time step.
      This paper presents a filtering strategy for the fully compressible equations
      based on normal-mode analysis that is used throughout the simulation to compute
      the fast dynamics and is able to damp only chosen modes. This method is based on
      an asymptotic analysis and respects the dynamics of gravity waves for thin
      layers. Finally, the filtering method is tested on a series of examples.

PMID- 19840981
TI  - Well-balanced compressible cut-cell simulation of atmospheric flow.
AB  - Cut-cell meshes present an attractive alternative to terrain-following
      coordinates for the representation of topography within atmospheric flow
      simulations, particularly in regions of steep topographic gradients. In this
      paper, we present an explicit two-dimensional method for the numerical solution
      on such meshes of atmospheric flow equations including gravitational sources.
      This method is fully conservative and allows for time steps determined by the
      regular grid spacing, avoiding potential stability issues due to arbitrarily
      small boundary cells. We believe that the scheme is unique in that it is
      developed within a dimensionally split framework, in which each coordinate
      direction in the flow is solved independently at each time step. Other notable
      features of the scheme are: (i) its conceptual and practical simplicity, (ii) its
      flexibility with regard to the one-dimensional flux approximation scheme
      employed, and (iii) the well-balancing of the gravitational sources allowing for
      stable simulation of near-hydrostatic flows. The presented method is applied to a
      selection of test problems including buoyant bubble rise interacting with
      geometry and lee-wave generation due to topography.

PMID- 19840982
TI  - Efficiency considerations in triangular adaptive mesh refinement.
AB  - Locally or adaptively refined meshes have been successfully applied to simulation
      applications involving multi-scale phenomena in the geosciences. In particular,
      for situations with complex geometries or domain boundaries, meshes with
      triangular or tetrahedral cells demonstrate their superior ability to accurately
      represent relevant realistic features. On the other hand, these methods require
      more complex data structures and are therefore less easily implemented,
      maintained and optimized. Acceptance in the Earth-system modelling community is
      still low. One of the major drawbacks is posed by indirect addressing due to
      unstructured or dynamically changing data structures and correspondingly lower
      efficiency of the related computations. In this paper, we will derive several
      strategies to circumvent the mentioned efficiency constraint. In particular, we
      will apply recent computational sciences methods in combination with results of
      classical mathematics (space-filling curves) in order to linearize the complex
      data and access structure.

PMID- 19840983
TI  - Anisotropic mesh adaptivity for multi-scale ocean modelling.
AB  - Research into the use of unstructured mesh methods in oceanography has been
      growing steadily over the past decade. The advantages of this approach for domain
      representation and non-uniform resolution are clear. However, a number of issues
      remain, in particular those related to the computational cost of models produced
      using unstructured mesh methods compared with their structured mesh counterparts.
      Mesh adaptivity represents an important means to improve the competitiveness of
      unstructured mesh models, where high resolution is only used when and where
      necessary. In this paper, an optimization-based approach to mesh adaptivity is
      described where emphasis is placed on capturing anisotropic solution
      characteristics. Comparisons are made between the results obtained with uniform
      isotropic resolution, isotropic adaptive resolution and fully anisotropic
      adaptive resolution.

PMID- 19840984
TI  - Space-time adaptive numerical methods for geophysical applications.
AB  - In this paper we present high-order formulations of the finite volume and
      discontinuous Galerkin finite-element methods for wave propagation problems with
      a space-time adaptation technique using unstructured meshes in order to reduce
      computational cost without reducing accuracy. Both methods can be derived in a
      similar mathematical framework and are identical in their first-order version. In
      their extension to higher order accuracy in space and time, both methods use
      spatial polynomials of higher degree inside each element, a high-order solution
      of the generalized Riemann problem and a high-order time integration method based
      on the Taylor series expansion. The static adaptation strategy uses locally
      refined high-resolution meshes in areas with low wave speeds to improve the
      approximation quality. Furthermore, the time step length is chosen locally
      adaptive such that the solution is evolved explicitly in time by an optimal time
      step determined by a local stability criterion. After validating the numerical
      approach, both schemes are applied to geophysical wave propagation problems such
      as tsunami waves and seismic waves comparing the new approach with the classical
      global time-stepping technique. The problem of mesh partitioning for large-scale
      applications on multi-processor architectures is discussed and a new mesh
      partition approach is proposed and tested to further reduce computational cost.

PMID- 19840985
TI  - A parallel second-order adaptive mesh algorithm for incompressible flow in porous
      media.
AB  - In this paper, we present a second-order accurate adaptive algorithm for solving
      multi-phase, incompressible flow in porous media. We assume a multi-phase form of
      Darcy's law with relative permeabilities given as a function of the phase
      saturation. The remaining equations express conservation of mass for the fluid
      constituents. In this setting, the total velocity, defined to be the sum of the
      phase velocities, is divergence free. The basic integration method is based on a
      total-velocity splitting approach in which we solve a second-order elliptic
      pressure equation to obtain a total velocity. This total velocity is then used to
      recast component conservation equations as nonlinear hyperbolic equations. Our
      approach to adaptive refinement uses a nested hierarchy of logically rectangular
      grids with simultaneous refinement of the grids in both space and time. The
      integration algorithm on the grid hierarchy is a recursive procedure in which
      coarse grids are advanced in time, fine grids are advanced multiple steps to
      reach the same time as the coarse grids and the data at different levels are then
      synchronized. The single-grid algorithm is described briefly, but the emphasis
      here is on the time-stepping procedure for the adaptive hierarchy. Numerical
      examples are presented to demonstrate the algorithm's accuracy and convergence
      properties and to illustrate the behaviour of the method.

PMID- 19840986
TI  - High-resolution spin-polarized scanning electron microscopy (spin SEM).
AB  - We have developed spin-polarized scanning electron microscopy (spin SEM) with a 5
      nm resolution. The secondary electron optics is very important, as it needs to
      transfer a sufficient number of secondary electrons to the spin polarimeter, due
      to the low efficiency of the polarimeter. The optics was designed using a three
      dimensional (3D) simulation program of the secondary electron trajectories, and
      it achieves highly efficient collection and transport of the secondary electrons
      even though the distance between the sample and the objective lens exit of the
      electron gun remains short. Moreover, the designed optics enables us to obtain
      clear SEM images in the spin SEM measurement and to precisely adjust the probe
      beam shape. These functions lead to images with high spatial resolution and
      sufficient signal-to-noise (S/N) ratios. This optics has been installed in an
      ultra-high vacuum (UHV) spin SEM chamber with a Schottky-type electron gun for
      the probe electron beam. We observed recorded bits on a perpendicular magnetic
      recording medium and visualized small irregularities in the bit shapes around the
      track edges and bit boundaries. The high resolution of 5 nm was demonstrated by
      observing the smallest domain composed by a single grain in the recording medium.

PMID- 19840987
TI  - KIT ligand and bone morphogenetic protein signaling enhances human embryonic stem
      cell to germ-like cell differentiation.
AB  - BACKGROUND: Signaling mechanisms involved in early human germ cell development
      are largely unknown and believed to be similar to mouse germ cell development;
      however, there may be species specific differences. KIT ligand (KITL) and Bone
      morphogenetic protein 4 (BMP4) are necessary in mouse germ cell development and
      may play an important role in human germ cell development. METHODS: KITL
      signaling studies were conducted by differentiating human embryonic stem cells
      (hESCs) on KITL wild-type, hetero- or homozygous knockout feeders for 10 days,
      and the effects of BMP signaling was determined by differentiation in the
      presence of BMP4 or its antagonist, Noggin. The formation of germ-like cells was
      ascertained by immunocytochemistry, flow cytometry and quantitative RT-PCR for
      germ cell markers. RESULTS: The loss of KITL in enrichment and differentiation
      cultures resulted in significant down-regulation of germ cell genes and a 70.5%
      decrease in germ-like (DDX4+ POU5F1+) cells, indicating that KITL is involved in
      human germ cell development. Moreover, endogenous BMP signaling caused germ-like
      (DDX4+ POU5F1+) cell differentiation, and the inhibition of this pathway caused a
      significant decrease in germ cell gene expression and in the number of DDX4+
      POU5F1+ cells. Further, we demonstrated that eliminating feeders but maintaining
      their secreted extracellular matrix is sufficient to sustain the increased
      numbers of DDX4+ POU5F1+ cells in culture. However, this resulted in decreased
      germ cell gene expression. CONCLUSIONS: From these studies, we establish that
      KITL and BMP4 germ cell signaling affects in vitro formation of hESC derived germ
      like cells and we suggest that they may play an important role in normal human
      germ cell development.

PMID- 19840988
TI  - Effects of oral contraceptives on diurnal profiles of insulin, insulin-like
      growth factor binding protein-1, growth hormone and cortisol in endurance
      athletes with menstrual disturbance.
AB  - BACKGROUND: Menstrual disturbances in female athletes are often explained as a
      consequence of energy deficiency. Oral contraceptive (OC) treatment may have
      favorable metabolic effects. We evaluated effects of OCs on diurnal secretions of
      insulin, insulin-like growth factor binding protein 1 (IGFBP-1), growth hormone
      (GH) and cortisol in relation to changes in body composition in athletes with
      menstrual disturbance compared with regularly menstruating athletes and controls.
      METHODS: Age- and BMI-matched groups of endurance athletes with menstrual
      disturbance (OAM, n = 9) and regularly cycling athletes (RM, n = 8) and sedentary
      controls (CTRL, n = 8) were examined, and hormone levels measured, before and
      after 8 months of treatment with a low-dose combined OC (30 microg ethinyl
      estradiol + 150 microg levonorgestrel). RESULTS: Before OC treatment, the diurnal
      profile of insulin was lower (P < 0.01) and levels of IGFBP-1 (P < 0.05) and
      cortisol (P < 0.05) were higher in OAM athletes than in CTRL, whereas GH
      secretion was higher than in RM athletes (P < 0.05). After treatment, diurnal
      secretions of these hormones were similar between groups with an increase of
      IGFBP-1 in the regularly menstruating subjects only (P < 0.001). OC treatment
      increased body fat mass in OAM athletes (P < 0.01 versus baseline). The change in
      total fat mass correlated positively with pretreatment diurnal levels of GH (r(s)
      = 0.67, P < 0.01) and cortisol (r(s) = 0.64, P < 0.01). CONCLUSIONS: OC treatment
      in endurance athletes with menstrual disturbance increases body fat mass and
      results in diurnal levels of insulin, IGFBP-1, GH and cortisol that are
      comparable to those in regularly menstruating subjects. These results suggest
      that OCs improve metabolic balance in OAM athletes.

PMID- 19840989
TI  - Children raised in mother-headed families from infancy: a follow-up of children
      of lesbian and single heterosexual mothers, at early adulthood.
AB  - BACKGROUND: The present investigation constituted the third phase of a
      longitudinal study of the quality of parent-child relationships and the
      psychological adjustment of children in female-headed families with no father
      present from infancy. METHODS: In this study, 27 families headed by single
      heterosexual mothers (solo mothers) and 20 families headed by lesbian mothers
      were compared with 36 two-parent heterosexual families as the child entered
      adulthood. Data were obtained from mothers and their young adult children by
      standardized interviews and questionnaires. RESULTS: The female-headed families
      were found to be similar to the traditional families on a range of measures of
      quality of parenting and young adults' psychological adjustment. Where
      differences were identified between family types, these pointed to more positive
      family relationships and greater psychological wellbeing among young adults
      raised in female-headed homes. CONCLUSIONS: The findings of this study show that
      children raised by solo heterosexual mothers or lesbian mothers from infancy
      continue to function well as they enter adulthood. The findings are of relevance
      to the UK Human Fertilisation and Embryology (2008) Act.

PMID- 19840990
TI  - Comparison of inter- and intra-cycle variability of anti-Mullerian hormone and
      antral follicle counts.
AB  - BACKGROUND: The antral follicle count (AFC) and anti-Mullerian hormone (AMH) both
      represent age-related follicular decline quite accurately, although long-term
      follow-up studies are still lacking. The best ovarian reserve test would need
      only a single, cycle-independent measurement to be representative. METHODS: To
      compare the inter- and intra-cycle stability of AFC and AMH, we used age-adjusted
      intra-class correlation coefficients (ICCs). To measure inter-cycle stability
      across a number of up to four menstrual cycles, we used data, prospectively
      collected for the purpose of an other study, from 77 regularly cycling, infertile
      women aged 24-40 years. AMH and AFC values were measured on cycle day 3. To study
      intra-cycle variability, we used data from a prospective cohort study of 44
      regularly cycling volunteers, aged 25-46 years and measured AMH and assessed the
      AFC (2-10 mm) every 1-3 cycle days. RESULTS: Between menstrual cycles, AFC and
      AMH varied between 0 and 25 follicles (median 10), and 0.3 and 27.1 ng/ml (median
      4.64). The difference in age-adjusted ICC between AMH [ICC, 0.89 (95% CI, 0.84
      0.94)] and AFC [ICC, 0.71 (95% CI, 0.63-0.77)] was 0.18 (95% CI, 0.12-0.27). For
      the intra-cycle variation, 0-43 antral follicles (median 7) were counted per
      volunteer. The difference in age-adjusted ICC between AMH [ICC, 0.87 (95% CI,
      0.82-0.91)] and AFC [ICC, 0.69 (95% CI, 0.46-0.82)] was 0.18 (95% CI, 0.034
      0.42). CONCLUSIONS: Serum AMH demonstrated less individual intra- and inter-cycle
      variation than AFCs and may therefore be considered a more reliable and robust
      means of assessing ovarian reserve in subfertile women.

PMID- 19840991
TI  - Long-term outcome of endoscopic dilatation in patients with Crohn's disease is
      not affected by disease activity or medical therapy.
AB  - BACKGROUND: Endoscopic dilatation of Crohn's disease-related strictures is an
      alternative to surgical resection in selected patients. The influence of disease
      activity and concomitant medical therapy on long-term outcomes is largely
      unknown. AIM AND METHODS: To study the long-term safety and efficacy of stricture
      dilatation in a single centre cohort. RESULTS: Between 1995 and 2006, 237
      dilatations where performed in 138 patients (mean age 50.6+/-13.4, 56% female)
      for a clinically obstructive stricture (<5 cm, 84% anastomotic). Immediate
      success of a first dilatation was 97% with a 5% serious complication rate. After
      a median follow-up of 5.8 years (IQR 3.0-8.4), recurrent obstructive symptoms led
      to a new dilatation in 46% or surgery in 24%. Niether elevated levels of C
      reactive protein nor endoscopic disease activity predicted the need for new
      intervention. None of the concomitant therapies influenced the outcome.
      CONCLUSION: This largest series ever reported confirms that long term efficacy of
      endoscopic dilatation of Crohn's disease outweighs the complication risk. Neither
      active disease at the time of dilatation nor medical therapy afterwards predict
      recurrent dilatation or surgery.

PMID- 19840993
TI  - Next steps for falls and fracture reduction.

PMID- 19840994
TI  - Storage and transpiration have negligible effects on delta13C of stem CO2 efflux
      in large conifer trees.
AB  - Stem respiration rates are often quantified by measuring the CO(2) efflux from
      stems into chambers. It has been suggested that these measurements underestimate
      respiration because some of the respired CO(2) can be either retained or
      transported upwards in the transpiration stream. If the stem CO(2) efflux does
      not represent all respired CO(2), then the interpretation of its isotopic signal
      may be compromised as well. The C-isotope composition of the respired CO(2) and
      the measured efflux could differ due to (i) the release of CO(2) produced
      elsewhere into the stem and transported upwards in xylem water (soil CO(2) or
      root respired CO(2)); (ii) the retention or release of CO(2) storage pools within
      the tree stem and (iii) the removal of CO(2) by the transpiration stream. We
      investigated the effects of these processes in large conifer trees using two
      manipulative experiments: a labelling experiment and a crown removal experiment.
      The labelling experiment used an extreme enrichment of dissolved CO(2) in soil
      water to assess the C uptake by the roots. In this experiment, we found no
      contamination of the stem CO(2) pool despite clear evidence that the water itself
      had been taken up. The crown removal experiment tested for vertical CO(2) flux in
      xylem water by eliminating transpiration. Here, we found no change in the
      delta(13)C of stem CO(2) efflux (delta(EA); P > 0.05). We concluded that for
      these large conifers, sap-flow influenced neither delta(13)C of stem efflux nor
      that of the stem CO(2) pool. By parameterizing Henry's Law for conditions inside
      the stem, we estimated the transport flux to represent 1-3% of the stem CO(2)
      efflux to the atmosphere. Finally, assuming a 2 per thousand difference between
      delta(13)C of root and stem respiration, we estimated that potential
      contamination of delta(EA) by root respired CO(2) would be < 0.1 per thousand.
      Thus, neither the release of soil or root CO(2), nor storage in the stem, nor
      vertical transport of CO(2) in the xylem sap had any detectable influence on
      delta(13)C of the CO(2) measured in stem efflux.

PMID- 19840995
TI  - Pinus pinaster seedlings and their fungal symbionts show high plasticity in
      phosphorus acquisition in acidic soils.
AB  - Young seedlings of maritime pine (Pinus pinaster Soland in Ait.) were grown in
      rhizoboxes using intact spodosol soil samples from the southwest of France, in
      Landes of Gascogne, presenting a large variation of phosphorus (P) availability.
      Soils were collected from a 93-year-old unfertilized stand and a 13-year-old P.
      pinaster stand with regular annual fertilization of either only P or P and
      nitrogen (N). After 6 months of culture in controlled conditions, different
      morphotypes of ectomycorrhiza (ECM) were used for the measurements of acid
      phosphatase activity and molecular identification of fungal species using
      amplification of the ITS region. Total biomass, N and P contents were measured in
      roots and shoots of plants. Bicarbonate- and NaOH-available inorganic P (Pi),
      organic P (Po) and ergosterol concentrations were measured in bulk and
      rhizosphere soil. The results showed that bulk soil from the 93-year-old forest
      stand presented the highest Po levels, but relatively higher bicarbonate
      extractable Pi levels compared to 13-year-old unfertilized stand. Fertilizers
      significantly increased the concentrations of inorganic P fractions in bulk soil.
      Ergosterol contents in rhizosphere soil were increased by fertilizer application.
      The dominant fungal species was Rhizopogon luteolus forming 66.6% of analysed ECM
      tips. Acid phosphatase activity was highly variable and varied inversely with
      bicarbonate-extractable Pi levels in the rhizosphere soil. Total P or total N in
      plants was linearly correlated with total plant biomass, but the slope was steep
      only between total P and biomass in fertilized soil samples. In spite of high
      phosphatase activity in ECM tips, P availability remained a limiting nutrient in
      soil samples from unfertilized stands. Nevertheless young P. pinaster seedlings
      showed a high plasticity for biomass production at low P availability in soils.

PMID- 19840996
TI  - Fluctuations in isometric muscle force can be described by one linear projection
      of low-frequency components of motor unit discharge rates.
AB  - The aim of the study was to investigate the relation between linear
      transformations of motor unit discharge rates and muscle force. Intramuscular
      (wire electrodes) and high-density surface EMG (13 x 5 electrode grid) were
      recorded from the abductor digiti minimi muscle of eight healthy men during 60 s
      contractions at 5%, 7.5% and 10% of the maximal force. Spike trains of a total of
      222 motor units were identified from the EMG recordings with decomposition
      algorithms. Principal component analysis of the smoothed motor unit discharge
      rates indicated that one component (first common component, FCC) described 44.2
      +/- 7.5% of the total variability of the smoothed discharge rates when computed
      over the entire contraction interval and 64.3 +/- 10.2% of the variability when
      computed over 5 s intervals. When the FCC was computed from four or more motor
      units per contraction, it correlated with the force produced by the muscle (62.7
      +/- 10.1%) by a greater degree (P < 0.001) than the smoothed discharge rates of
      individual motor units (41.4 +/- 7.8%). The correlation between FCC and the force
      signal increased up to 71.8 +/- 13.1% when the duration and the shape of the
      smoothing window for discharge rates were similar to the average motor unit
      twitch force. Moreover, the coefficients of variation (CoV) for the force and for
      the FCC signal were correlated in all subjects (R(2) range = 0.14-0.56; P < 0.05)
      whereas the CoV for force was correlated to the interspike interval variability
      in only one subject (R(2) = 0.12; P < 0.05). Similar results were further
      obtained from measures on the tibialis anterior muscle of an additional eight
      subjects during contractions at forces up to 20% of the maximal force (e.g. FCC
      explained 59.8 +/- 11.0% of variability of the smoothed discharge rates). In
      conclusion, one signal captures most of the underlying variability of the low
      frequency components of motor unit discharge rates and explains large part of the
      fluctuations in the motor output during isometric contractions.

PMID- 19840997
TI  - AMP-activated protein kinase inhibits TREK channels.
AB  - AMP-activated protein kinase (AMPK) is a serine/threonine kinase activated by
      conditions that increase the AMP : ATP ratio. In carotid body glomus cells, AMPK
      is thought to link changes in arterial O(2) with activation of glomus cells by
      inhibition of unidentified background K(+) channels. Modulation by AMPK of
      individual background K(+) channels has not been described. Here, we characterize
      effects of activated AMPK on recombinant TASK-1, TASK-3, TREK-1 and TREK-2
      background K(+) channels expressed in HEK293 cells. We found that TREK-1 and TREK
      2 channels but not TASK-1 or TASK-3 channels are inhibited by AMPK. AMPK-mediated
      inhibition of TREK involves key serine residues in the C-terminus that are also
      known to be important for PKA and PKC channel modulation; inhibition of TREK-1
      requires Ser-300 and Ser-333 and inhibition of TREK-2 requires Ser-326 and Ser
      359. Metabolic inhibition by sodium azide can also inhibit both TREK and TASK
      channels. The effects of azide on TREK occlude subsequent channel inhibition by
      AMPK and are attenuated by expression of a dominant negative catalytic subunit of
      AMPK (dnAMPK), suggesting that metabolic stress modulates TREK channels by an
      AMPK mechanism. By contrast, inhibition of TASK channels by azide was unaffected
      by expression of dnAMPK, suggesting an AMPK-independent mechanism. In addition,
      prolonged exposure (6-7 min) to hypoxia ( = 11 +/- 1 mmHg) inhibits TREK channels
      and this response was blocked by expression of dnAMPK. Our results identify a
      novel modulation of TREK channels by AMPK and indicate that select residues in
      the C-terminus of TREK are points of convergence for multiple signalling cascades
      including AMPK, PKA and PKC. To the extent that carotid body O(2) sensitivity is
      dependent on AMPK, our finding that TREK-1 and TREK-2 channels are inhibited by
      AMPK suggests that TREK channels may represent the AMPK-inhibited background K(+)
      channels that mediate activation of glomus cells by hypoxia.

PMID- 19840998
TI  - Quantitative dynamics and spatial profile of perisomatic GABAergic input during
      epileptiform synchronization in the CA1 hippocampus.
AB  - Perisomatic GABAergic input appears spared or even increased in intractable
      temporal lobe epilepsy, and has been suggested to contribute to the generation of
      pathological discharges. Nevertheless, its degree of functional activity during
      epileptiform synchronization has not been thoroughly investigated. Thus, it
      remains unclear how structural preservation or loss of domain-specific GABAergic
      input may affect the network. Here, we have taken advantage of a model of
      epileptiform activity in vitro to quantify the charge transfer provided by
      perisomatic GABA(A) receptor-mediated input to CA1 pyramidal neurons during
      interictal-like bursts. By recording both firing in GABAergic interneurons and
      the charge transfer generated by unitary postsynaptic currents to target
      pyramidal cells, we have estimated the charge transfer that would be dynamically
      generated by the recruitment of the entire pool of perisomatic-targeting
      interneurons and the number of perisomatic-targeting interneurons that would be
      required to generate the experimentally observed GABAergic input. In addition, we
      have recorded and compared the dynamics and charge density of GABAergic input
      recorded at different membrane compartments such as the soma vs. the proximal
      dendrite. Our results suggest that GABA(A) receptor-mediated perisomatic input is
      massively activated during burst synchronization and that its kinetic properties
      and charge density are similar at the soma and proximal dendrite. These
      functional results match structural data published by other laboratories very
      well and strengthen the hypothesis that the potential preservation of perisomatic
      GABAergic input in intractable epilepsies may be a key factor in the generation
      of pathological network activity.

PMID- 19840999
TI  - Excitation of locus coeruleus noradrenergic neurons by thyrotropin-releasing
      hormone.
AB  - Locus coeruleus (LC) noradrenergic neurons are implicated in a variety of
      functions including the regulation of vigilance and the modulation of sensory
      processing. Thyrotropin-releasing hormone (TRH) is an endogenous neuropeptide
      that induces a variety of behavioural changes including arousal and
      antinociception. In the present study, we explored whether the activity of LC
      noradrenergic neurons is modulated by TRH. Using current-clamp recording from
      isolated rat LC neurons, we found that TRH increased the firing rate of
      spontaneous action potentials. The TRH action was mimicked by TRH analogues
      including taltirelin and TRH-gly. In voltage-clamp recording at a holding
      potential of 50 mV, TRH produced an inward current associated with a decrease in
      the membrane K+ conductance. This current was inhibited by the TRH receptor
      antagonist chlordiazepoxide. Following inhibition of the pH-sensitive K+
      conductance by extracellular acidification, the TRH response was fully inhibited.
      The TRH-induced current was also inhibited by the phospholipase C (PLC) inhibitor
      U-73122, but not by the protein kinase C inhibitor chelerythrine nor by chelation
      of intracellular Ca2+ by BAPTA. The recovery from the facilitatory action of TRH
      on the spike frequency was markedly inhibited by a high concentration of
      wortmannin. These results suggest that TRH activates LC noradrenergic neurons by
      decreasing an acid-sensitive K+ conductance via PLC-mediated hydrolysis of
      phosphatidylinositol 4,5-bisphosphate. The present findings demonstrate that TRH
      activates LC neurons and characterize the underlying signalling mechanisms. The
      action of TRH on LC neurons may influence a variety of CNS functions related to
      the noradrenergic system which include arousal and analgesia.

PMID- 19841001
TI  - Prevalence, incidence and risk factors for hepatitis C in homosexual men: data
      from two cohorts of HIV-negative and HIV-positive men in Sydney, Australia.
AB  - BACKGROUND: An increasing incidence of hepatitis C virus (HCV) infection in HIV
      positive homosexual men has recently been described, but it is uncertain to what
      extent this reflects sexual transmission. We report prevalence, incidence and
      risk factors for HCV infection in community-based cohorts of HIV-negative and HIV
      positive homosexual men in Sydney. METHODS: Both cohorts recruited participants
      using similar community-based strategies. Men underwent annual face-to-face
      interviews, and reported history of injecting-drug use (IDU) and sexual and other
      behaviours that might lead to blood contact. HCV screening was offered to
      consenting participants from 2001 to 2007. RESULTS: At baseline, HCV prevalence
      was 1.07% in the HIV-negative and 9.39% in the HIV-positive men. HCV
      seropositivity was strongly associated with a history of IDU in both cohorts
      (OR=56.18, 95% CI 12.55 to 251.5 in HIV-negative, and OR=24.46, 95% CI 5.44 to
      110.0 in HIV-positive). In the HIV-negative cohort, five men seroconverted to HCV
      over 4412.1 person-years of follow-up, an incidence of 0.11 per 100 person-years
      (95% CI 0.03 to 0.26). Only one seroconverter reported IDU. Of the five, four
      reported sexual contact with HIV-positive men (HR=8.23, 95% CI 0.91 to 74.28),
      and two had an incident ulcerative sexually transmitted infection. In the HIV
      positive cohort, none seroconverted over 238.1 person-years of follow-up (97.5%
      CI 0 to 1.54, single-sided). CONCLUSION: HCV prevalence was almost 10 times
      higher in HIV-positive homosexual men. Although incident HCV infection was
      uncommon in both cohorts, cases of non-IDU-related transmission did occur,
      possibly linked to sexual contact with HIV-positive men.

PMID- 19841000
TI  - Redox modulation of global phosphatase activity and protein phosphorylation in
      intact skeletal muscle.
AB  - Skeletal muscles produce transient reactive oxygen species (ROS) in response to
      intense stimulation, disuse atrophy, heat stress, hypoxia, osmotic stress,
      stretch and cell receptor activation. The physiological significance is not well
      understood. Protein phosphatases (PPases) are known to be highly sensitive to
      oxidants and could contribute to many different signalling responses in muscle.
      We tested whether broad categories of PPases are inhibited by levels of acute
      oxidant exposure that do not result in loss of contractile function or gross
      oxidative stress. We also tested if this exposure results in elevated levels of
      global protein phosphorylation. Rat diaphragm muscles were treated with either
      2,3-dimethoxy-1-naphthoquinone (DMNQ; 1, 10, 100 microm; a mitochondrial O(2)(.
      )/H2O2 generator) or exogenous H2O2 (5, 50, 500 microm) for 30 min. Supernatants
      were assayed for serine/threonine PPase (Ser/Thr-PPase) or protein tyrosine PPase
      (PTP) activities. With the exception of 500 microm H2O2, no other oxidant
      exposures significantly elevated protein carbonyl formation, nor did they alter
      the magnitude of twitch force. DMNQ significantly decreased all categories of
      PPase activity at 10 and 100 microm and reduced PTP at 1 microm. Similar
      reductions in Ser/Thr-PPase activity were seen in response to 50 and 500 microm
      H2O2 and PTP at 500 microm H2O2. ROS treatments resulted a dose-dependent
      increase in the phosphorylation states of many proteins. The data are consistent
      with the concept that PPases, within intact skeletal muscles, are highly
      sensitive to acute changes in ROS activity and that localized ROS play a critical
      role in lowering the barriers for effective phosphorylation events to occur in
      muscle cells, thus increasing the probability for cell signalling responses to
      proceed.

PMID- 19841002
TI  - Direct impression on agar surface as a diagnostic sampling procedure for candida
      balanitis.
AB  - BACKGROUND: The diagnosis of candida balanitis should be based upon both clinical
      and mycological data. The procedure of material collection is a critical issue to
      confirm or rule out the clinical diagnosis of candida balanitis. OBJECTIVE: To
      compare direct impression of the glans on the agar surface of solid culture media
      with the collection of genital exudates with cotton swab for the diagnosis of
      candida balanitis. METHODS: A prospective cross-sectional study was carried out
      during a 36-month period. Sexually transmitted disease clinic attendees with
      balanitis and asymptomatic men were included. Specimens for yeast culture were
      collected from the glans penis and inner preputial layer using the direct
      impression on CHROMagar candida medium and by swabbing with a sterile cotton
      swab. RESULTS: Among 478 men enrolled, 189 had balanitis. The prevalence of
      candida balanitis was 17.8% (85/478) confirmed after culture by direct
      impression; the swab method detected only 54/85 (63.5%) of these men. Of the 289
      asymptomatic men, 36 (12.5%) yielded Candida spp; the swab method detected only
      38.9% of these men. The risk of having candida balanitis is 8.9 (IC 95% 2.48 to
      32.04) whenever the number of candida colonies recovered by direct impression was
      greater than 10. CONCLUSIONS: Direct impression on CHROMagar candida medium
      resulted in the highest Candida spp recovery rate. More than 10 colonies yielded
      by impression culture were statistically associated with candida balanitis. This
      method shows the ideal profile for sampling the male genital area for yeasts and
      should be included in the management of balanitis.

PMID- 19841003
TI  - Prevalence, incidence and risk factors for pharyngeal gonorrhoea in a community
      based HIV-negative cohort of homosexual men in Sydney, Australia.
AB  - BACKGROUND: Pharyngeal gonorrhoea is common in homosexual men and may be
      important in maintaining community prevalence of anogenital infections. METHODS:
      From 2003, all participants in the Health in Men cohort of HIV-negative
      homosexual men in Sydney were offered annual pharyngeal gonorrhoea screening by
      BD ProbeTec nucleic acid amplification (NAAT) assay with supplementary porA
      testing. Participants self-reported diagnoses of pharyngeal gonorrhoea made
      elsewhere between interviews. Detailed sexual behavioural data were collected 6
      monthly. RESULTS: Among 1427 participants enrolled, 65 study-visit-diagnosed
      pharyngeal gonorrhoea infections were identified (incidence 1.51 per 100 person
      years, 95% CI 1.19 to 1.93) of which seven infections were identified on baseline
      testing (prevalence 0.57%, 95% CI 0.23 to 1.17%). Almost 85% of study-visit
      diagnosed pharyngeal infections occurred without concurrent anogenital
      gonorrhoea. The combined incidence of study-visit-diagnosed and self-reported
      pharyngeal gonorrhoea (n=193) was 4.45 per 100 person-years (95% CI 3.86 to
      5.12). On multivariate analysis, incident infection was associated with younger
      age (p-trend=0.001), higher number of male partners (p-trend=0.002) and reported
      contact with gonorrhoea (p<0.001). Insertive oro-anal sex ('rimming') was the
      only sexual behaviour independently associated with incident pharyngeal
      gonorrhoea (p-trend=0.044). CONCLUSIONS: The majority of pharyngeal gonorrhoea
      occurred without evidence of concurrent anogenital infection, and the high
      incidence-to-prevalence ratio suggests frequent spontaneous resolution of NAAT
      detected infection. The association of pharyngeal gonorrhoea with oro-anal sex
      indicates that a broader range of sexual practices are likely to be involved in
      transmission of gonorrhoea to the pharynx than previously acknowledged. Screening
      the pharynx of sexually active homosexual men could play a role in reducing the
      prevalence of anogenital Neisseria gonorrhoeae.

PMID- 19841004
TI  - Is use of the human papillomavirus vaccine among female college students related
      to human papillomavirus knowledge and risk perception?
AB  - BACKGROUND: Few studies have examined factors associated with the actual use of
      the human papillomavirus (HPV) vaccine since licensure in 2006. The aims of this
      study were to assess HPV vaccination rates and to examine whether knowledge and
      risk perceptions regarding HPV were associated with the reported use of the HPV
      vaccine among female college students. METHODS: Using a cross-sectional design,
      406 women aged 18-26 years were recruited at two public universities and
      completed a self-administered survey. Respondents who reported having received at
      least one dose of HPV vaccine were classified as 'vaccinated' (n=177, 43.6%).
      Responses, stratified by the receipt of HPV vaccine, were compared using
      descriptive statistics and multivariate models. RESULTS: Based on multivariate
      logistic regression modelling, 18-year-old women were approximately four times
      more likely to report use of the HPV vaccine compared with respondents aged 19-26
      years. Respondents who correctly indicated that HPV caused genital warts were
      1.85 times more likely (adjusted odds ratio (OR) 1.85, 95% CI 1.20 to 2.93) to
      have received at least one HPV vaccine. African American and Asian women were
      each less likely to be vaccinated compared with white women. Risk perception was
      not significantly associated with vaccine uptake, however, the majority of
      respondents failed accurately to recognise their high risk of both acquiring and
      transmitting HPV. CONCLUSIONS: These findings suggest knowledge deficits and
      misperceptions about HPV risk as potential themes for educational campaigns
      encouraging the greater use of the preventive HPV vaccine among this subgroup.

PMID- 19841006
TI  - H1N1 vaccination begins as proportion of cases in hospital admitted to intensive
      care rises.

PMID- 19841008
TI  - Cryptosporidiosis.

PMID- 19841007
TI  - Risk of bias versus quality assessment of randomised controlled trials: cross
      sectional study.
AB  - OBJECTIVES: To evaluate the risk of bias tool, introduced by the Cochrane
      Collaboration for assessing the internal validity of randomised trials, for inter
      rater agreement, concurrent validity compared with the Jadad scale and Schulz
      approach to allocation concealment, and the relation between risk of bias and
      effect estimates. DESIGN: Cross sectional study. Study sample 163 trials in
      children. MAIN OUTCOME MEASURES: Inter-rater agreement between reviewers
      assessing trials using the risk of bias tool (weighted kappa), time to apply the
      risk of bias tool compared with other approaches to quality assessment (paired t
      test), degree of correlation for overall risk compared with overall quality
      scores (Kendall's tau statistic), and magnitude of effect estimates for studies
      classified as being at high, unclear, or low risk of bias (metaregression).
      RESULTS: Inter-rater agreement on individual domains of the risk of bias tool
      ranged from slight (kappa=0.13) to substantial (kappa=0.74). The mean time to
      complete the risk of bias tool was significantly longer than for the Jadad scale
      and Schulz approach, individually or combined (8.8 minutes (SD 2.2) per study v
      2.0 (SD 0.8), P<0.001). There was low correlation between risk of bias overall
      compared with the Jadad scores (P=0.395) and Schulz approach (P=0.064). Effect
      sizes differed between studies assessed as being at high or unclear risk of bias
      (0.52) compared with those at low risk (0.23). CONCLUSIONS: Inter-rater agreement
      varied across domains of the risk of bias tool. Generally, agreement was poorer
      for those items that required more judgment. There was low correlation between
      assessments of overall risk of bias and two common approaches to quality
      assessment: the Jadad scale and Schulz approach to allocation concealment.
      Overall risk of bias as assessed by the risk of bias tool differentiated effect
      estimates, with more conservative estimates for studies at low risk.

PMID- 19841009
TI  - Tobacco sponsorship of tennis tournament goes ahead because of weak Swiss
      legislation, says campaigning group.

PMID- 19841010
TI  - Bans on public smoking reduce deaths among people exposed to secondhand smoke,
      study shows.

PMID- 19841011
TI  - Comments on Bithell, J. F., Keegan, T. J., Kroll, M. E., Murphy, M. F. G. and
      Vincent, T. J., Childhood leukaemia near British nuclear installations:
      methodological issues and recent results. Radiat. Prot. Dosimetry 132(2), 191-197
      (2008).

PMID- 19841012
TI  - Gamma spectroscopic analysis and associated radiation hazards of building
      materials used in Egypt.
AB  - Radiation exposure of the population can be increased appreciably by the use of
      building materials containing above-normal levels of naturally occurring
      radionuclides of terrestrial origin. Using gamma-ray spectrometry, the natural
      radioactivity levels of 55 samples of natural and manufactured Egyptian building
      materials have been investigated. The samples were collected from local market
      and construction sites. From the measured gamma-ray spectra, activity
      concentrations were determined. The activities were in the ranges 11.7-35.6, 12.4
      55.2 and 60-350 Bq kg(-1) for (226)Ra, (232)Th and (40)K, respectively. The
      activities are compared with available reported data from other countries and
      with the world average value for soils. The radium equivalent activity Ra(eq),
      the external hazard index H(ex) and the absorbed dose rate in air D in each
      sample was evaluated to assess the radiation hazard for people living in
      dwellings made of the materials studied. All building materials have shown Ra(eq)
      (range from 37.76 to 116.87 Bq kg(-1)) lower than the limit of 370 Bq kg(-1)
      adopted by the Organization for Economic Cooperation and Development (OECD). The
      absorbed dose rate in indoor air is lower than the international recommended
      value of 55 nGy h(-1) for all test samples. All the materials examined are
      acceptable for use as building materials as defined by the OECD criterion.

PMID- 19841013
TI  - Noise model application to small hydroelectrical power plants impact evaluation
      in the Aosta Valley territory.
AB  - In this paper measurements, results and model estimates, with reference to
      hydroelectric power plant noise emissions in the Aosta Valley territory, are
      compared in different contexts. The analysis was performed to evaluate and point
      out the influence of the noise source context on the accuracy of the model
      results. The estimates were implemented considering power plants as: point
      sources and area sources taking (or not) into account the building elements of
      the plant. This method allowed evaluating the detail that is suitable to achieve
      in an estimate and to justify possible simplifications in this kind of noise
      source description. Noise measurements were carried out simultaneously, at
      different distances from the power plants that were taken into account. The
      measurement results at the closest points to the sources were used as the model
      input data, while the levels found at the other points were used for comparison
      with the estimate results.

PMID- 19841014
TI  - Radon monitoring in water sources of Balakot and Mansehra cities lying on a
      geological fault line.
AB  - This paper relates to a series of systematic studies regarding measurement of
      radon concentration in the earthquake-affected areas of northern Pakistan. Radon
      is a radioactive alpha-particle-emitting gas originating from the decay series of
      uranium and thorium and is found anywhere in soil, air and water. The nature of
      water does not matter with regard to the presence of radon, however, the level of
      radon concentration varies in different types of water. The present survey is
      carried out in water samples from the fault zone of Balakot and Mansehra regions,
      North West Frontier Province, Pakistan, which is important for geological
      consideration and protection from radiation hazards. The measurements were made
      on a Pylon system that is based on the radon gas measurement with a Lucas cell.
      In 72 water samples in the equilibrium state between radon and its progeny, the
      concentration level of radon is measured. The results show that the radon
      concentrations are in the range of 4.99-24.52 kBq/m(3), with an average value of
      15.52 kBq/m(3) for all types of water taken in this survey.

PMID- 19841015
TI  - Management of NORM-containing processing residuals from hydrocarbons extraction
      and treatment plants.
AB  - Eni, in collaboration with ARPA Veneto, laid down a procedure for the exposure
      assessment of workers and the public to natural radionuclides contained in oil
      sludge during their future removal from hydrocarbons extraction and treatment
      plants. Reference legislation for this study is Italian Legislative Decree
      241/00, which regulates protection from exposure to ionising radiation also for
      working activities with naturally occurring radioactive materials.

PMID- 19841016
TI  - A simplified procedure for dosimetric evaluations on ELF sources with complex
      waveforms.
AB  - The endorsement of the 2004/40 European Directive has renewed the interest in
      numerical electromagnetic dosimetry. In this field, a need is clearly perceived
      for dosimetric approaches able to reduce costs and the time necessary for this
      type of evaluations. In the low and intermediate frequency ranges, EM dosimetry
      makes use of quasi-static techniques in the frequency domain, which become
      onerous when dealing with sources emitting multiple frequencies. A procedure is
      then proposed, able to greatly simplify the numerical process needed to perform a
      dosimetric calculation involving a complex waveform. The procedure is based on
      the use of an 'equivalent' field intensity at an arbitrarily chosen 'reference'
      frequency and allows executing a single-frequency dosimetric evaluation able to
      take into account, with some approximations, the complete spectral contents of
      the source signal.

PMID- 19841017
TI  - Quantitative evaluation of personal exposure to UV radiation of workers and
      general public.
AB  - Due to meteorological conditions variability and to the variability of exposure
      patterns, which can be largely different during a working day, personal
      dosemeters use can be necessary to obtain a correct quantitative evaluation of
      the radiation dose absorbed by an exposed worker. Different classes of personal
      dosemeters exist and, among them, electronic dosemeters and polysulphone film
      dosemeters. An experimental campaign is presented conduced in a cultivated area
      of Tuscany and some aspects are discussed about an experimental campaign
      performed on a population of volunteers on a central Italy beach near Rome. The
      aim of the present work is to show some relevant issues in a dosimetric approach
      to the exposure evaluation of outdoor workers and, in general, of the public
      during recreational activities.

PMID- 19841018
TI  - Noise action plan of agglomerations: sustainable hypothesis or utopy?
AB  - European and Italian laws establish that agglomerations of more than 100 000
      inhabitants must adopt an action plan in order to manage noise issues and
      effects. The plan aim is to reduce population exposure to environmental noise,
      which is defined as the outdoor sound created by human activities, including
      noise emitted by road traffic, rail traffic and air traffic, and noise from sites
      of industrial activity. Although acoustic pollution represents one of the main
      causes of annoyance for inhabitants of urban areas, the political agenda does not
      acknowledge it among the main environmental issues. Thus, acoustic reclamation is
      often considered a duty to be accomplished rather than a way to improve quality
      of life for citizens. Furthermore, financial resources are generally very poor
      while the acoustic critical situations are numerous and serious in terms of
      exceeding the limit. In this situation, what is the meaning of an urban area
      noise action plan? What are the concrete actions that municipalities can realise
      to reduce urban noise pollution? This study tries to answer these questions,
      starting from the analysis carried out for the action plan of the city of Turin.

PMID- 19841019
TI  - Review of open problems in assessing compliance with 2004/40/EC directive
      exposure limit values for low-frequency current density by means of numerical
      techniques.
AB  - The endorsement process of the 2004/40/EC Directive (still in progress) has led
      to a critical analysis of the ICNIRP Guidelines, on which the directive is based.
      In particular, some known problems affect the applicability of the numerical
      techniques needed for checking compliance with limits at low frequency. A review
      of these open problems is presented in the paper, highlighting how such problems
      deal more with pre-processing and post-processing steps than with the core
      numerical calculation of the current density.

PMID- 19841020
TI  - Enacting death in the intensive care unit: medical technology and the multiple
      ontologies of death.
AB  - This article explores various ways health personnel enact death in connection
      with mechanical ventilation treatment withdrawal in the intensive care unit (ICU)
      at Trondheim University Hospital. The main focus is on sedated terminal patients
      who undergo mechanical ventilator treatment withdrawal and relatives' presence at
      this time. Mol's (2002) praxiographic orientation of the actor-network approach
      is followed while exploring this medical practice. Utilizing this
      interdisciplinary science and technology studies approach this article describes
      what Timmermans and Berg (2003) have called ' technology-in-practice'. Thus the
      main focus of the analysis is on medical interventions, and enactments of death
      within medical practice. The article argues against a 'social essentialist'
      approach to medical technology, which views technology as a passive force
      empowered by social relations. It explores how various enactments of death are
      intrinsically linked with and shaped by the use of medical technology within
      clinical practice. A praxiographic inquiry into how death is enacted carefully
      takes notice of how medical practice and techniques make death audible, tangible,
      visible, knowable and real. Mol's praxiographic approach also enables a
      description of how the multiple enactments of death connect within end-of-life
      care through various forms of coordination. This article is based on interviews
      with 28 nurses and two physicians in a Norwegian intensive care unit.

PMID- 19841021
TI  - A metasynthesis of midwives' experience of hospital practice in publicly funded
      settings: compliance, resistance and authenticity.
AB  - Worldwide, increasing percentages of women are giving birth in centralized
      hospitals in the belief that this maximizes safety for themselves and their
      babies. In parallel, there is international recognition that the number of birth
      interventions used in the routine care of labouring women is rising. This is
      fuelling concern about iatrogenesis, and, particularly, maternal and infant
      morbidity and mortality. It also has an adverse impact on the economics of health
      care. National and international policy characterizes midwives as the guardians
      of normal childbirth. This guardianship appears to be failing. The objective of
      this metasynthesis is to explore midwives' perceptions of hospital midwifery with
      a focus on labour ward practice to examine professional discourses around
      midwifery work in the current modernist, risk averse and consumerist childbirth
      context. Based on an iterative search strategy, 14 studies were selected for the
      metasynthesis. Three overarching themes were identified: 'power and control';
      'compliance with cultural norms'; and 'attempting to normalize birth'. Most
      midwives aimed to provide what they characterized as 'real midwifery' but this
      intention was often overwhelmed with heavy workloads and the normative pressure
      to provide equitable care to all women. This raises questions of authenticity,
      both in terms of midwives living out their beliefs, and in terms of
      acknowledgement of the power to resist. The theoretical insights generated by the
      metasynthesis could have resonance for other professional and occupational groups
      who wish to offer autonomous individualized services in an increasingly risk
      averse target driven global society.

PMID- 19841022
TI  - Identities under construction: women hailed as addicts.
AB  - Despite continuing investigations of the efficacy of Canadian addiction treatment
      services and supports across a range of health care settings and socio-cultural
      groups, many systemic, geographic and ideological barriers to service provision
      for women still exist. Determining how current services and supports can become
      more congruent with women's gender-specific needs is a current research focus.
      Drawing on Butler's reformulation of Althusser's interpellation, this article
      explores the power of hailing, where hailing power lies, and how hailing operates
      in discourses about addiction that appear in women's talk of their encounters
      with addiction services and supports. The article briefly outlines Butler's
      understanding of interpellation and examines ways by which gender operates as
      both condition and effect in women becoming addicts. I argue that women's
      narratives reveal patterns of interaction that intersect and generate complex
      social meanings and identities, and serve to get women's attention in terms of
      seeing themselves as addicts. Further, I argue that powerful competing discourses
      concerning gender and the medicalization of addiction, hailed through these
      interactions, are taken up as lived realities by some women and resisted by
      others. Knowing how women are hailed to take up as their own, or resist, aspects
      of traditional and gendered discourses within addiction treatment and recovery
      communities can inform gender-compassionate service provision.

PMID- 19841023
TI  - Spaces of care in the third sector: understanding the effects of
      professionalization.
AB  - Increasingly the health and welfare needs of individuals and communities are
      being met by third sector, or not-for-profit, organizations. Since the 1980s
      third sector organizations have been subject to significant, sector-wide changes,
      such as the development of contractual funding and an increasing need to
      collaborate with governments and other sectors. In particular, the processes of
      'professionalization' and 'bureaucratization' have received significant attention
      and are now well documented in third sector literature. These processes are often
      understood to create barriers between organizations and their community groups
      and neutralize alternative forms of service provision. In this article we provide
      a case study of an Australian third sector organization undergoing
      professionalization. The case study draws on ethnographic and qualitative
      interviews with staff and volunteers at a health-based third sector organization
      involved in service provision to marginalized community groups. We examine how
      professionalization alters organizational spaces and dynamics and conclude that
      professionalized third sector spaces may still be 'community' spaces where
      individuals may give and receive care and services. Moreover, we suggest that
      these community spaces hold potential for resisting the neutralizing effects of
      contracting.

PMID- 19841024
TI  - Food allergy and food intolerance: towards a sociological agenda.
AB  - This article asks what sociological insights an analysis of food allergy and food
      intolerance might afford. We outline the parameters of debates around food
      allergy and food intolerance in the immunological, clinical and epidemiological
      literatures in order to identify analytic strands which might illuminate our
      sociological understanding of the supposed increase in both. Food allergy and
      food intolerance are contested and contingent terms and it is salient that the
      term true food allergy is replete throughout medico-scientific, epidemiological
      and popular discourses in order to rebuff spurious or 'nonallergic' claims of
      food-related symptoms. Complexity theory is introduced as a means of gaining
      analytic purchase on the food allergy debate. The article concludes that the use
      of this perspective provides a contemporary example of the 'double hermeneutic',
      in that the meanings and interpretations of contemporary explanations of food
      allergy are both permeated by, and can be made sense of, through recourse to
      complexity thinking.

PMID- 19841025
TI  - Amputations in PAD patients: data from the German Federal Statistical Office.
AB  - Much effort has been spent to reduce the number of amputees within the last two
      decades, but it remains unclear how effective the different strategies have been.
      We analyzed the prevalence of amputations in inpatient cases in the federal
      statistics. Detailed lists of all amputations coded as major amputations (OPS 5
      864) and minor amputations (OPS 5-865) performed in 2005 and 2006, divided into
      the 4th and 5th number of the OPS-code, were provided by the Federal Statistical
      Office. In 2006, a total of 62,880 amputations affecting the lower extremities
      (2005: 63,005) were performed in Germany. Because of multiple amputations within
      a single case the corresponding cases amounted to 55,705 in 2006 and 55,689 in
      2005. Based on these data age-adjusted incidence rates of major amputations per
      100,000 inhabitants increased from 2 at the age of < 50 years to 201 at the age
      of > 80 years. For minor amputations the prevalence rates increased from 4 at the
      age of < 50 years to 209 at the age of > 80 years. It can be assumed that
      peripheral arterial disease or neurovascular disease as the underlying disease
      necessitating the amputation were present in 74.9% of all inpatient cases who
      finally underwent amputation. There were 12.9% with non-vascular or non-diabetic
      reasons for amputations. In patients presenting with gangrene, the rate of minor
      amputations decreased with age, whereas the rate of major amputations increased,
      especially within the 8th to 10th decades of life. In conclusion, amputations
      affecting the lower limbs are still a relevant problem in Germany. At the time of
      an aging German population it has to be an important goal to lower or at least to
      stabilize the rate of amputations. The DRG statistics enable the Federal Ministry
      of Health and health politics to monitor amputation rates easily.

PMID- 19841026
TI  - The efficacy and safety of enhanced external counterpulsation in patients with
      peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is common in patients with severe coronary
      artery disease (CAD) and is considered a relative contraindication to external
      enhanced counterpulsation (EECP), but there are no data that define the efficacy
      and safety of EECP in patients with PAD. The International EECP Patient Registry
      (IEPR) was used to compare initial post-therapy and 2-year follow-up clinical
      outcomes and adverse event rates in patients with and without PAD. From January
      2002 to October 2004, 2126 patients were enrolled in the IEPR, of whom 493 (23%)
      had a history of PAD. Immediately following EECP, the reduction in angina (> or =
      1 Canadian Cardiovascular Society class) was similar in patients with and without
      PAD (76.6% vs 79.0%, p = 0.27) as was improvement in the Duke Activity Score
      Index (DASI) score (+4.7% vs +6.1%, p < 0.001). Both angina reduction and DASI
      score improvement were sustained at 2 years. PAD patients discontinued EECP more
      frequently (12.0% vs 8.5%, p < 0.05), but lower extremity ulceration did not
      occur more frequently in patients with PAD (3.7% vs 2.7%, p = 0.26). Rates of
      death (17.1% vs 8.6%, p < 0.001) and myocardial infarction (9.5% vs 5.0%, p <
      0.001) were, as expected, higher in patients with PAD compared to patients
      without PAD at 2 years. In conclusion, while PAD patients constitute a high-risk
      cohort with known higher adverse event rates, EECP led to similar short- and long
      term improvements in angina and quality of life for individuals with PAD compared
      to those without PAD.

PMID- 19841028
TI  - Effects of socioeconomic position on 30-day mortality and wait for surgery after
      hip fracture.
AB  - OBJECTIVE: In countries where the National Health Service provides universal
      health coverage, socioeconomic position should not influence the quality of
      health care. We examined whether socioeconomic position plays a role in short
      term mortality and waiting time for surgery after hip fracture. DESIGN:
      Retrospective cohort study. SETTING: and participants From the Hospital
      Information System database, we selected all patients, aged at least 65 years and
      admitted to acute care hospitals in Rome for a hip fracture between 1 January
      2006 and 30 November 2007. The socioeconomic position of each individual was
      obtained using a city-specific index of socioeconomic variables based on the
      individual's census tract of residence. MAIN OUTCOME MEASURES: Three different
      outcomes were defined: waiting times for surgery, mortality within 30 days and
      intervention within 48 h of hospital arrival for hip fracture. We used a logistic
      regression to estimate 30-day mortality and a Cox proportional hazard model to
      calculate hazard ratios of intervention within 48 h. Median waiting times were
      estimated by adjusted Kaplan-Meyer curves. Analyses were adjusted for age, gender
      and coexisting medical conditions. RESULTS: Low socioeconomic level was
      significantly associated with higher risk of mortality [adjusted relative risk
      (RR) = 1.51; P < 0.05] and lower risk of early intervention (adjusted RR = 0.32;
      P < 0.001). Socioeconomic level had also an effect on waiting times within 30
      days. CONCLUSIONS: Individuals living in disadvantaged census tracts had poorer
      prognoses and were less likely than more affluent people to be treated according
      to clinical guidelines despite universal healthcare coverage.

PMID- 19841029
TI  - Improving the quality of mental health care.
AB  - OBJECTIVE: To develop international guidance for improving the quality of mental
      health care in low- and middle-income countries. DESIGN: A panel developed
      recommendations based on a comprehensive literature review, consultation with
      over 100 experts from 46 countries and an analysis of international best
      practices. Recommendations A 5-pronged approach to improving the quality of
      mental health care is recommended. Quality improvement requires the alignment of
      policy and legislation with the attainment of good quality mental health
      outcomes. Key partners must be brought into the quality improvement process.
      Funding can be an important tool for promoting good quality but needs to be
      correctly aligned to meet policy objectives and to promote evidence-based
      interventions. Accreditation procedures and quality standards need to be
      carefully developed and resources allocated for their implementation. Finally,
      quality improvement must be brought into routine service management and delivery.
      CONCLUSIONS: Through a systematic approach to quality improvement, it is possible
      to ensure that the best possible interventions are provided within the
      constraints of each country and that the rights and well-being of people with
      mental disorders is optimally promoted. Quality improvement is not a luxury but
      an integral part of ensuring that the best possible services are provided to all
      who need them.

PMID- 19841030
TI  - Comment on: Developments in outpatient parenteral antimicrobial therapy (OPAT)
      for Gram-positive infections in Europe, and the potential impact of daptomycin.

PMID- 19841027
TI  - Impact and preventability of adverse events in Spanish public hospitals: results
      of the Spanish National Study of Adverse Events (ENEAS).
AB  - OBJECTIVE: To determine the impact and preventability of adverse events (AEs)
      associated with health care in Spanish hospitals. DESIGN: Retrospective cohort
      study. SETTING: Twenty-four Spanish hospitals. PARTICIPANTS: Patients of any age
      with a clinical record indicating an inpatient stay of >24 h and a discharge
      between 4 and 10 June 2005 (n = 5908). INTERVENTION: None. MAIN OUTCOME MEASURES:
      Percentage of AEs considered preventable. RESULTS: We were able to identify 525
      patients suffering AEs associated directly with medical care, who accumulated 655
      AEs with 43% of these AEs considered preventable. Overall, 45% (295 AEs) were
      considered minor, 39% (255 AEs) moderate and 16% (105 AEs) severe. There were no
      significant differences in AE severity by hospital size, but AEs associated with
      surgical services were more likely to be severe than those associated with
      medical services. Some 31.4% of AEs resulted in a longer stay and 23.4% led to
      hospital admission. AEs associated with medical care caused 6.1 additional days
      per patient. Of the patients, 66.3% required additional procedures and 69.9%
      required additional treatments. Incidence of death in patients with AEs was 4.4%
      (CI 95%: 2.8-6.5). Age over 65 was associated with a higher incidence of
      preventable AEs. The highest percentages of preventable AEs were related to
      diagnosis (84.2%), to nosocomial infections (56.6%) and to care (56%).
      CONCLUSIONS: In Spanish hospitals, AEs associated with health care cause
      distress, disability, death, lengthen hospital stay and cause increased
      consumption of health-care resources. A relatively high percentage of AEs in
      Spain may be preventable with improvements in medical care.

PMID- 19841031
TI  - An EORTC Phase II study of caspofungin as first-line therapy of invasive
      aspergillosis in haematological patients.
AB  - OBJECTIVES: Caspofungin was evaluated as first-line monotherapy of invasive
      aspergillosis (IA) in patients with haematological malignancies and undergoing
      autologous transplants. METHODS: Adults with proven or probable IA, defined
      strictly according to EORTC-MSG criteria, were eligible. Those with possible IA
      were enrolled, but were not evaluable for efficacy unless upgraded to
      proven/probable disease within 7 days of registration based on investigations
      performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1)
      followed by 50 mg/day. The primary endpoint was the proportion of patients with
      complete or partial response at the end of caspofungin therapy in the modified
      intention to treat (MITT) group; secondary endpoints were response and survival
      at day 84 and safety. RESULTS: In the MITT group (n = 61), 75% of patients had
      cancer not in remission (relapsing or refractory), 85% were neutropenic at
      enrolment and 49% had a Karnofsky score of < or =50. At end of treatment, 1 and
      19 patients had complete and partial response, respectively [success rate 33%
      (20/61)], 9 (15%) achieved stabilization and 31 (51%) had disease progression.
      One patient was not evaluable. The 6 and 12 week survival rates were 66% (40/61)
      and 53% (32/60), respectively. Baseline characteristics associated with survival
      at day 84 were an underlying disease in remission (not relapsing or refractory)
      and Karnofsky score. Recovery from neutropenia at the end of treatment was also
      significantly associated with survival. No serious drug-related adverse events or
      discontinuations due to drug-related adverse events were observed. CONCLUSIONS:
      Caspofungin provided an observed response rate compatible with the null
      hypothesis of a true response rate of < or =35%. Underlying disease-related
      factors had a major impact on results.

PMID- 19841032
TI  - Dominant frequency of atrial fibrillation correlates poorly with atrial
      fibrillation cycle length.
AB  - BACKGROUND: Localized sites of high frequency during atrial fibrillation (AF) are
      used as target sites to eliminate AF. Spectral analysis is used experimentally to
      determine these sites. The purpose of this study was to compare dominant
      frequencies (DF) with AF cycle length (AFCL) of unipolar and bipolar recordings.
      METHODS AND RESULTS: Left and right atrial endocardial electrograms were recorded
      during AF in 40 patients with lone AF, using two 20-polar catheters. Mean age was
      53+/-9.9 years. Unipolar and bipolar electrograms were recorded simultaneously
      during 16 seconds at 2 right and 4 left atrial sites. AFCLs and DFs were
      determined. QRS subtraction was performed in unipolar signals. DFs were compared
      with mean, median, and mode of AFCLs; 4800 unipolar and 2400 bipolar electrograms
      were analyzed. Intraclass correlation was poor for all spectral analysis
      protocols. Best correlation was accomplished with DFs from unipolar electrograms
      compared with median AFCL (intraclass correlation coefficient, 0.67). A gradient
      in median AFCL of >25% was detected in 16 of 40 patients. In 13 of 16 patients
      (81%) with a frequency gradient of >25%, the site with highest frequency was
      located in the left atrium (posterior left atrium in 8 patients). The site with
      shortest median AFCL and highest DF corresponded in 25% if unipolar and in 31% if
      bipolar electrograms were analyzed. CONCLUSIONS: DFs from unipolar and bipolar
      electrograms recorded during AF correlated poorly with mean, median, and mode
      AFCL. If a frequency gradient >25% existed, the site with highest DF corresponded
      to the site of shortest median AFCL in only 25% of patients. Because spectral
      analysis is being used to identify ablation sites, these data may have important
      clinical implications.

PMID- 19841033
TI  - Electroanatomic mapping and radiofrequency ablation of porcine left atria and
      atrioventricular nodes using magnetic resonance catheter tracking.
AB  - BACKGROUND: The MRI-compatible electrophysiology system previously used for MR
      guided left ventricular electroanatomic mapping was enhanced with improved MR
      tracking, an MR-compatible radiofrequency ablation system and higher-resolution
      imaging sequences to enable mapping, ablation, and ablation monitoring in smaller
      cardiac structures. MR-tracked navigation was performed to the left atrium (LA)
      and atrioventricular (AV) node, followed by LA electroanatomic mapping and
      radiofrequency ablation of the pulmonary veins (PVs) and AV node. METHODS AND
      RESULTS: One ventricular ablation, 7 PV ablations, 3 LA mappings, and 3 AV node
      ablations were conducted. Three MRI-compatible devices (ablation/mapping
      catheter, torqueable sheath, stimulation/pacing catheter) were used, each with 4
      to 5 tracking microcoils. Transseptal puncture was performed under x-ray, with
      all other procedural steps performed in the MRI. Preacquired MRI roadmaps served
      for real-time catheter navigation. Simultaneous tracking of 3 devices was
      performed at 13 frames per second. LA mapping and PV radiofrequency ablation were
      performed using tracked ablation catheters and sheaths. Ablation points were
      registered and verified after ablation using 3D myocardial delayed enhancement
      and postmortem gross tissue examination. Complete LA electroanatomic mapping was
      achieved in 3 of 3 pigs, Right inferior PV circumferential ablation was achieved
      in 3 of 7 pigs, with incomplete isolation caused by limited catheter deflection.
      During AV node ablation, ventricular pacing was performed, 3 devices were
      simultaneously tracked, and intracardiac ECGs were displayed. 3D myocardial
      delayed enhancement visualized node injury 2 minutes after ablation. AV node
      block succeeded in 2 of 3 pigs, with 1 temporary block. CONCLUSIONS: LA mapping,
      PV radiofrequency ablation, and AV node ablation were demonstrated under MRI
      guidance. Intraprocedural 3D myocardial delayed enhancement assessed lesion
      positional accuracy and dimensions.

PMID- 19841034
TI  - Tlr2 is critical for diet-induced metabolic syndrome in a murine model.
AB  - Obesity and its associated comorbidities, termed metabolic syndrome, are
      increasingly prevalent, and they pose a serious threat to the health of
      individuals and populations. Gene-environment interactions have been scrutinized
      since the kinetics of the increased prevalence of obesity would argue against a
      purely genetic etiology. Toll-like receptors (TLRs), widely expressed and highly
      conserved transmembrane receptors, are at the intersection of diet and
      metabolism, and may therefore be important determinants of weight gain and its
      sequellae. We sought specifically to determine the role of Tlr2 in the
      development of obesity and metabolic syndrome utilizing two dietary models that
      approximate contemporary diet compositions. Using C57BL/6 Hsd mice (wild type,
      WT) and mice with a targeted mutation in Tlr2 (Tlr2(-/-)), we showed that mice
      lacking TLR2 are substantially protected from diet-induced adiposity, insulin
      resistance, hypercholesterolemia, and hepatic steatosis. In adipose tissue, Tlr2
      deletion was associated with attenuation of adipocyte hypertrophy, as well as
      diminished macrophage infiltration and inflammatory cytokine expression.-Himes,
      R. W., Smith, C. W. Tlr2 is critical for diet-induced metabolic syndrome in a
      murine model.

PMID- 19841035
TI  - Generation of transgenic plants expressing antibodies to the environmental
      pollutant microcystin-LR.
AB  - We describe the engineering, regeneration, and characterization of transgenic
      tobacco plants expressing a recombinant antibody specific to microcystin-LR (MC
      LR), the environmental toxin pollutant produced by species of cyanobacteria. The
      antibody was created by a genetic fusion of the antigen-binding regions of the
      microcystin-specific single-chain antibody, 3A8, with constant regions from the
      murine IgG1kappa, Guy's 13. IgG transgenes were controlled by a leader peptide
      that targets the transgene products to the secretory pathway and also allows for
      rhizosecretion. The antibody, extracted from the leaves or rhizosecreted into
      hydroponic medium by transgenic plants, was shown to have functional binding to
      MC-LR. Antibody yields in transgenic plant leaves reached a maximum of 64
      microg/g leaf fresh weight (0.6% total soluble protein), and the rate of antibody
      rhizosecretion reached a maximum of 5 microg/g root dry weight/24 h.
      Rhizosecreted antibody bound to MC-LR in hydroponic medium, and transgenic plants
      grew more efficiently on medium containing MC-LR compared to wild-type controls.
      This proof of concept paves the way for applications to produce diagnostic
      antibodies to microcystin-LR, remove it from the environment by phytoremediation,
      or enhance yields in crops exposed to MC-LR.-Drake, P. M. W., Barbi, T., Drever,
      M. R., van Dolleweerd, C. J., Porter, A. J. R., Ma, J. K.-C. Generation of
      transgenic plants expressing antibodies to the environmental pollutant
      microcystin-LR.

PMID- 19841037
TI  - Fail-safe termination elements: a common feature of the eukaryotic genome?
AB  - A recent scan of the human genome (1) identified approximately 11 million
      hairpins. Some have been linked to known sequences, such as viruses, transposable
      elements, and, more recently, regulating or microRNAs, but the significance, if
      any, of most sequences that can be predicted to form hairpins remains unknown.
      Here we show that hairpins that are cleaved by RNase III- like nucleases can
      induce termination, even with normally polyadenylated transcripts, and that a
      cleaved hairpin downstream of a normal termination signal can induce fail-safe
      termination. Because such cleavage sites appear common to intergenic regions, the
      results raise the possibility that similar fail-safe termination elements are
      widely distributed in the eukaryotic genome to prevent read-through transcription
      from disrupting downstream promoter elements or opposing transcription.-Nabavi,
      S., Nazar, R. N. Fail-safe termination elements: a common feature of the
      eukaryotic genome?

PMID- 19841036
TI  - CD14 inhibition efficiently attenuates early inflammatory and hemostatic
      responses in Escherichia coli sepsis in pigs.
AB  - Sepsis is a severe infection-induced systemic inflammatory syndrome. Inhibition
      of downstream inflammatory mediators of sepsis, e.g., TNF-alpha, has failed in
      clinical trials. The aim of this study was to investigate the effects of
      inhibiting CD14, a key upstream innate immunity molecule, on the early
      inflammatory and hemostatic responses in a pig model of gram-negative sepsis. The
      study comprised two arms, whole live Escherichia coli bacteria and E. coli
      lipopolysaccharide (LPS) (n=25 and n=9 animals, respectively). The animals were
      allocated into treatment (anti-CD14) and control (IgG isotype or saline) groups.
      Inflammatory, hemostatic, physiological, and microbiological parameters were
      measured. The proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IL-8, but
      not the anti-inflammatory cytokine IL-10, were efficiently inhibited by anti
      CD14. Furthermore, anti-CD14 preserved the leukocyte count and significantly
      reduced granulocyte enzyme matrix metalloproteinase-9 release and expression of
      the granulocyte membrane activation molecule wCD11R3 (pig CD11b). The hemostatic
      markers thrombin-antithrombin III complexes and plasminogen activator inhibitor-1
      were significantly attenuated. Anti-CD14 did not affect LPS or E. coli DNA
      levels. This study documents that CD14 inhibition efficiently attenuates the
      proinflammatory cytokine response and granulocyte activation and reverses the
      procoagulant state but does not interfere with LPS levels or bacterial counts in
      E. coli-induced sepsis.-Thorgersen, E. B., Hellerud, B. C., Nielsen, E. W.,
      Barratt-Due, A., Fure, H., Lindstad, J. K., Pharo, A., Fosse, E., Tonnessen, T.
      I., Johansen, H. T., Castellheim, A., Mollnes, T. E. CD14 inhibition efficiently
      attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis
      in pigs.

PMID- 19841039
TI  - Balancing rigor against the inherent limitations of investigating hard-to-reach
      populations.
AB  - Maintaining rigor in research is critical; however, this need must be balanced by
      the necessity of conducting studies in populations where inherent barriers exist
      relative to key issues such as recruitment, attrition, sampling, sample size,
      assessment techniques, psychometric rigor, the identification of mediators and
      moderators and the practical relevance of the research question itself.
      Ultimately, the value of a study in health promotion should be judged on the
      practicality of the research question within the context of the target
      population. Striking the perfect balance between rigor and practicality to the
      field is a question that health promotion researchers and professionals need to
      determine through ongoing dialogue and debate.

PMID- 19841038
TI  - ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the
      late but not the early events of the NK-cell activating synapse.
AB  - Natural killer (NK) cells play a crucial role in the antitumoral responses
      through cytolytic function and cytokine production. Expression of HLA-G at the
      surface of tumoral cells confers a protection against NK-cell cytolysis through
      its interaction with the ILT2 inhibitory receptor. Even though the role of this
      interaction on the inhibition of NK-cell cytotoxicity is well established, its
      effect on the molecular events occurring at the NK/target-cell synapse is not
      well characterized. We found that the interaction of the inhibitory receptor ILT2
      with HLA-G inhibited the polarization of NK-cell lytic granules and the
      microtubule organizing center (MTOC) as well as the accumulation of filamentous
      actin (F-actin) at the area of contact. However, it did not affect the
      recruitment of the activatory receptor CD2 at the NK/target-cell interface. Even
      though CD2 was accumulated to the NK-cell synapse, the interaction of ILT2 with
      HLA-G efficiently inhibited intracellular calcium mobilization and IFN-gamma
      polarized production of NK cells. These results indicate that while the ILT2/HLA
      G interaction leads to the inhibition of NK-cell functions, it displays
      differential effects on cytoskeleton reorganization and CD2 localization at the
      NK-cell synapse.-Favier, B., LeMaoult, J., Lesport, E., Carosella, E. D. ILT2/HLA
      G interaction impairs NK-cell functions through the inhibition of the late but
      not the early events of the NK-cell-activating synapse.

PMID- 19841040
TI  - Factors influencing the adoption of a health promoting school approach in the
      province of Quebec, Canada.
AB  - This study examined a prediction model that integrated three categories of
      predictors likely to influence adoption of the Quebec Healthy Schools (HS)
      approach, i.e. attributes of the approach, individual and contextual
      characteristics. HS receptivity was considered as a potential mediator. For this
      study, 141 respondents representing 96 schools participated in a postal survey.
      We used bivariate logistic regression to assess factors associated with HS
      adoption and Baron and Kenny's method to test the mediation effect of HS
      receptivity. Four predictors related to school organizational characteristics had
      more weight in influencing the adoption of HS: the 'presence of leaders within
      schools', 'perceived school contextual barriers', 'school investment in healthy
      lifestyles' and 'beliefs in collective efficacy'. The influence of the latter two
      predictors was not direct but mediated by HS receptivity. Our findings showed
      that standard attributes generally considered as predictors of the adoption of an
      innovation are not the strongest determinants to explain HS adoption in the
      present context. The results shed light on the crucial role of organizational
      context in the adoption of this type of approach.

PMID- 19841041
TI  - Investigating message-framing effects in the context of a tailored intervention
      promoting physical activity.
AB  - Health-promoting messages can be framed in terms of the gains associated with
      healthy behaviour or the losses associated with unhealthy behaviour. It has been
      argued that gain-framed messages promoting physical activity (PA) are more
      effective than loss-framed messages, but empirical findings are inconsistent.
      Also, no previous studies investigated the effects of gain- and loss-framed
      messages in the context of a computer-tailored PA intervention. In this study, we
      provided participants with computer-generated tailored feedback concerning their
      PA levels. In total, 787 participants entered in the study, of whom 299 completed
      all measures at a 3-month follow-up. We investigated whether gain- and loss
      framed messages promoting PA affected information acceptance, attitude, intention
      and behaviour differently. The results showed that gain-framed messages resulted
      in stronger intentions to be physically active than loss-framed messages. This
      did not result in a significant increase in actual PA, however, as measured by a
      3-month follow-up assessment. For information acceptance and attitude, a non
      significant advantage of gain-framed messages was found. All effects had small
      effect sizes. Thus, whereas gain-framed information might be more persuasive than
      loss-framed information when it comes to promoting PA, the differences between
      gain- and loss-framed messages are likely to be small.

PMID- 19841042
TI  - Marine omega-3 fatty acid intake: associations with cardiometabolic risk and
      response to weight loss intervention in the Look AHEAD (Action for Health in
      Diabetes) study.
AB  - OBJECTIVE: To examine usual marine omega-3 fatty acid (mO-3FA) intake in
      individuals with diabetes; its association with adiposity, lipid, and glucose
      control; and its changes with behavioral lifestyle intervention for weight loss.
      RESEARCH DESIGN AND METHODS: Cross-sectional and 1-year longitudinal analyses
      were performed on 2,397 Look AHEAD (Action for Health in Diabetes) participants.
      Look AHEAD is a cardiovascular outcome trial evaluating the effects of intensive
      lifestyle intervention for weight loss in overweight/obese subjects with type 2
      diabetes. RESULTS: Baseline mO-3FA intake was 162 +/- 138 mg/day. It was
      inversely associated with triglycerides (beta = -0.41, P < 0.001) and weakly with
      HDL (beta = 4.14, P = 0.050), after multiple covariate adjustment. One-year mO
      3FA and fried/sandwich fish intake decreased with intensive lifestyle
      intervention (P < 0.001). CONCLUSIONS: mO-3FA intake in Look AHEAD participants
      was low but associated favorably with lipids. These results encourage
      investigation on the potential benefits of increasing mO-3FA intake in lifestyle
      interventions for weight loss in individuals with diabetes.

PMID- 19841043
TI  - Serum 25(OH)D3 vitamin status of elderly Finnish women is suboptimal even after
      summer sunshine but is not associated with bone density or turnover.
AB  - OBJECTIVE: Concentrations of 50 and 75 nmol/l are proposed as serum 25
      hydroxyvitamin D (25(OH)D) target for older people from the view of bone health.
      We evaluated vitamin D status of elderly Finnish women in light of these
      definitions, its relationship to bone mineral density (BMD) and turnover, and
      improvement by summer sunshine. DESIGN: Population-based study. METHODS: A total
      of 1604 ambulatory women aged 62-79 years were studied; 66% used vitamin D
      supplements. Serum 25(OH)D(3) was measured with HPLC before and after summer, and
      heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I
      procollagen aminoterminal propeptide (PINP) were analyzed. RESULTS: In spring,
      60.3% of the women had 25(OH)D(3) <or=50 nmol/l, and the target of 75 nmol/l was
      reached by 9.1%. For supplement users, the respective numbers were 52.1 and
      11.9%. Serum 25(OH)D(3) did not determine BMD or bone turnover measured by serum
      PINP. Summer sunshine increased serum 25(OH)D(3) by 17.4% (P<0.0001), but in
      autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement
      users, PTH remained stable but decreased in others during summer (P=0.025).
      CONCLUSIONS: Vitamin D status of elderly Finnish women is suboptimal if
      25(OH)D(3) levels of 50 or 75 nmol/l are used as a threshold. It is moderately
      increased by supplement intake and summer sunshine. However, 25(OH)D(3)
      concentrations did not influence bone density in terms of serum PINP and bone
      turnover rate.

PMID- 19841044
TI  - Overweight is associated with impaired beta-cell function during pregnancy: a
      longitudinal study of 553 normal pregnancies.
AB  - OBJECTIVE: To monitor beta-cell function and insulin sensitivity longitudinally
      in a large cohort of pregnant women to elucidate mechanisms that influence
      glycemic control in pregnancy. DESIGN AND METHODS: Five hundred and fifty-three
      pregnant Scandinavian women underwent 75 g oral glucose tolerance test (OGTT) at
      weeks 14-16 and 30-32. Insulin sensitivity (Matsuda index) and beta-cell function
      (ratio of AUC(insulin) to AUC(glucose), AUC(ins/glc)) were calculated from 520
      complete tests, and subsequently beta-cell function was adjusted for insulin
      sensitivity, rendering an oral disposition index (DI(o)). RESULTS: Eleven women
      (2.1%) had gestational diabetes mellitus (GDM1) at weeks 14-16, and 49 (9.4%) at
      weeks 30-32 (GDM2), which is higher than that previously reported in this region.
      In the subdivision of OGTT, more overweight (body mass index>25) was found in
      glucose-intolerant groups (glucose-tolerant women (normal glucose tolerance, NGT)
      38 versus GDM2 women 58 and GDM1 women 82%, P<0.005). In early pregnancy, insulin
      sensitivity was lowest in GDM1, intermediate in GDM2, and highest in NGT. In late
      pregnancy, insulin sensitivity decreased in all groups, most in gestational
      diabetes. beta-cell function demonstrated minor shifts during pregnancy, but when
      adjusted for decreasing insulin sensitivity, DI(o) levels fell by 40% (P<0.001).
      DI(o) was significantly attenuated relative to glucose intolerance (GDM1 25% and
      GDM2 53%) during pregnancy. In overweight women, DI(o) levels were lower
      throughout pregnancy (P<0.001 versus normal weight women), this reduction was
      significant (P<0.01) in both NGT (21-25%) and GDM2 subjects (26-49%). CONCLUSION:
      beta-cell function adjusted for insulin sensitivity (DI(o)) deteriorated during
      pregnancy in both glucose-tolerant and glucose-intolerant women. The failure to
      compensate the decrease in insulin sensitivity was accentuated in overweight
      women.

PMID- 19841045
TI  - Metformin: an old medication of new fashion: evolving new molecular mechanisms
      and clinical implications in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is now recognized to be the most common
      endocrinopathy in women of reproductive age with a prevalence of 6.6-6.8%. PCOS,
      a syndrome of unknown etiology, was initially regarded as a reproductive
      disorder. However, in the last 15 years the role of insulin resistance (IR) has
      been identified as a significant contributor to the pathogenesis of PCOS, and the
      metabolic and cardiovascular sequelae of the syndrome have been increasingly
      appreciated. The coexistence and interaction of reproductive and cardiometabolic
      abnormalities in the context of PCOS have created a need for a modified
      therapeutic management of affected women. Insulin sensitizers, particularly
      metformin, have been introduced as a pharmaceutical option targeting not only IR,
      but several other aspects of the syndrome, including reproductive abnormalities.
      The landscape of the multifaceted actions of metformin evolves to broaden the
      therapeutic implications of this old drug in a new fashion for patients with
      PCOS. Most recently, the spectrum of metformin's targets has been expanded, and
      molecular studies have explored the tissue-specific mechanisms of metformin in
      the liver, the muscle, the endothelium, and the ovary. The use of metformin in
      pregnant women with PCOS comprises another scarcely explored, but promising area
      of research. This review attempts to cover the spectrum of metformin's cellular
      actions in different tissues and to summarize the current literature regarding
      the potential medical value of this medication in PCOS. Even if many of these
      actions are individually modest, they seem to be collectively sufficient to
      confer therapeutic benefits not only in cardiometabolic aspects but also in
      reproductive aspects of PCOS.

PMID- 19841047
TI  - Prosecutorial decision making in Taiwan: A partial test of Black's behavior of
      law.
AB  - Most prior studies have examined prosecutorial decision making from cognitive,
      organizational, and legal perspectives, with few studies applying a broad
      sociological model. This study attempts to address the gap by using Black's
      Behavior of Law as a theoretical framework to explicate prosecutorial behavior.
      With analysis of aggregate-level data from Taiwan for the period 1973 to 2005,
      the results partially support Black's propositions. Organization (martial law)
      and culture (educational attainment) are significantly associated with the levels
      of change in prosecutors' behavior in the directions hypothesized using Black's
      model. The remaining aspects of social life, however, do not have an effect on
      the prosecutors' decisions during the time frame. The findings suggest that
      mediating variables, such as the extent of governmental autocracy and control
      over legislative policy, need to be considered in explaining the behavior of law.

PMID- 19841046
TI  - Adiponectin: serum levels, promoter polymorphism, and associations with birth
      size and cardiometabolic outcome in young adults born large for gestational age.
AB  - OBJECTIVE: To assess whether the -11391G>A polymorphism in the regulatory region
      of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth,
      adiponectinemia, and cardiometabolic risk in adult life. DESIGN: Case-control
      study nested within a prospective cohort of 2063 community subjects born in
      1978/1979 and followed since birth to date. METHODS: ADIPOQ -11391G>A genotype
      phenotype associations were evaluated in 116 subjects born large for gestational
      age (LGA) and 392 gender-matched controls at birth (birth size), at 8-10 years
      (catch-down growth), and at 23-25 years of age (cardiometabolic profile).
      RESULTS: The -11391A variant allele frequency was higher in LGA subjects
      (P=0.04). AA genotype was associated with augmented probability of being born LGA
      (odds ratio=4.14; 95% confidence interval: 1.16-16.7; P=0.03). This polymorphism
      was associated neither with body composition nor with postnatal growth pattern.
      At the age of 23-25 years, the -11391A variant allele was associated with higher
      serum adiponectin levels (GG: 10.7+/-6.2 versus GA: 12.2+/-6.5 versus AA: 14.2+/
      6.8 microg/ml; P<0.01). Subjects born LGA presented higher body mass index (BMI;
      P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and
      homeostasis assessment model for insulin resistance (P=0.01) than adequate for
      gestational age. Symmetry at birth did not influence these variables. The
      occurrence of catch-down of weight was associated with lower BMI and abdominal
      circumference (P<0.001) at 23-25 years. CONCLUSIONS: The -11391A ADIPOQ gene
      variant was associated with increased chance of being born LGA and with higher
      adiponectin levels in early adult life.

PMID- 19841048
TI  - Prison to society: a mixed methods analysis of coping with reentry.
AB  - This research investigates how individuals who reenter society from prison use
      coping strategies. Participants are incarcerated individuals who recidivated
      following a previous release from prison (n = 20). Participants examine their
      most recent reentry experience via an interview. The research question under
      investigation is, "What themes describe how individuals cope with reentry from
      prison to society?" Data and results combine qualitative and quantitative
      analysis methods. The predominant coping strategy for dealing with reentry
      barriers is avoidance. There is a defined process experienced by participants,
      which is initial optimism about release, followed by craving substances, facing
      practical barriers, and/or feeling overwhelmed. This eventually results in
      avoidance of managing problems and emotions and substance abuse relapse, which
      culminates in recidivism.

PMID- 19841049
TI  - The changing landscape of crack cocaine use and HIV infection.

PMID- 19841050
TI  - Doctors in detention and the Hippocratic Oath.

PMID- 19841052
TI  - Smoking of crack cocaine as a risk factor for HIV infection among people who use
      injection drugs.
AB  - BACKGROUND: Little is known about the possible role that smoking crack cocaine
      has on the incidence of HIV infection. Given the increasing use of crack cocaine,
      we sought to examine whether use of this illicit drug has become a risk factor
      for HIV infection. METHODS: We included data from people participating in the
      Vancouver Injection Drug Users Study who reported injecting illicit drugs at
      least once in the month before enrolment, lived in the greater Vancouver area,
      were HIV-negative at enrolment and completed at least 1 follow-up study visit. To
      determine whether the risk of HIV seroconversion among daily smokers of crack
      cocaine changed over time, we used Cox proportional hazards regression and
      divided the study into 3 periods: May 1, 1996-Nov. 30, 1999 (period 1), Dec. 1,
      1999-Nov. 30, 2002 (period 2), and Dec. 1, 2002-Dec. 30, 2005 (period 3).
      RESULTS: Overall, 1048 eligible injection drug users were included in our study.
      Of these, 137 acquired HIV infection during follow-up. The mean proportion of
      participants who reported daily smoking of crack cocaine increased from 11.6% in
      period 1 to 39.7% in period 3. After adjusting for potential confounders, we
      found that the risk of HIV seroconversion among participants who were daily
      smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03,
      95% confidence interval [CI] 0.57-1.85; period 2: HR 1.68, 95% CI 1.01-2.80; and
      period 3: HR 2.74, 95% CI 1.06-7.11). INTERPRETATION: Smoking of crack cocaine
      was found to be an independent risk factor for HIV seroconversion among people
      who were injection drug users. This finding points to the urgent need for
      evidence-based public health initiatives targeted at people who smoke crack
      cocaine.

PMID- 19841054
TI  - Governments make inroads into medical self-regulation.

PMID- 19841053
TI  - Prevention of osteoporosis-related fractures among postmenopausal women and older
      men.

PMID- 19841055
TI  - Dispatch from the medical front. Summer plans.

PMID- 19841056
TI  - Aboriginal groups seek representation on Pan-Canadian Public Health Network.

PMID- 19841057
TI  - Local control over Aboriginal health care improves outcome, study indicates.

PMID- 19841058
TI  - The effects of sap ionic composition on xylem vulnerability to cavitation.
AB  - Recent evidence of ion-mediated changes in pit membrane porosity suggests that
      plants may modulate the hydraulic conductance of their xylem conduits. Under the
      current paradigm, membrane porosity also determines conduit vulnerability to
      water stress-induced cavitation. Therefore, the hypothesis of an ion-mediated
      regulation of xylem vulnerability to cavitation in trees was tested. Segments of
      five Angiosperm and two Gymnosperm species were infiltrated with ultra-pure
      deionized water as a reference fluid or with a 50 mM KCl solution. KCl had a
      strong impact on segment conductance with either a positive or a negative effect
      across species. When 1 mM CaCl2 was added to the reference solution, the effect
      of KCl was minimized for most species. By contrast, segment vulnerability to
      cavitation was only slightly influenced by the presence of KCl in the solution.
      From this it was concluded that the mechanisms controlling pit membrane
      permeability to water flow and its resistance to the penetration of air bubbles
      are largely uncoupled, which suggests that the hypothesis of a porous structure
      of pit membranes should be revisited.

PMID- 19841059
TI  - In vitro hepatic metabolism explains higher clearance of voriconazole in children
      versus adults: role of CYP2C19 and flavin-containing monooxygenase 3.
AB  - Voriconazole is a broad spectrum antifungal agent for treating life-threatening
      fungal infections. Its clearance is approximately 3-fold higher in children
      compared with adults. Voriconazole is cleared predominantly via hepatic
      metabolism in adults, mainly by CYP3A4, CYP2C19, and flavin-containing
      monooxygenase 3 (FMO3). In vitro metabolism of voriconazole by liver microsomes
      prepared from pediatric and adult tissues (n = 6/group) mirrored the in vivo
      clearance differences in children versus adults, and it showed that the oxidative
      metabolism was significantly faster in children compared with adults as indicated
      by the in vitro half-life (T(1/2)) of 33.8 + or - 15.3 versus 72.6 + or - 23.7
      min, respectively. The K(m) for voriconazole metabolism to N-oxide, the major
      metabolite formed in humans, by liver microsomes from children and adults was
      similar (11 + or - 5.2 versus 9.3 + or - 3.6 microM, respectively). In contrast,
      apparent V(max) was approximately 3-fold higher in children compared with adults
      (120.5 + or - 99.9 versus 40 + or - 13.9 pmol/min/mg). The calculated in vivo
      clearance from in vitro data was found to be approximately 80% of the observed
      plasma clearance values in both populations. Metabolism studies in which CYP3A4,
      CYP2C19, or FMO was selectively inhibited provided evidence that contribution of
      CYP2C19 and FMO toward voriconazole N-oxidation was much greater in children than
      in adults, whereas CYP3A4 played a larger role in adults. Although expression of
      CYP2C19 and FMO3 is not significantly different in children versus adults, these
      enzymes seem to contribute to higher metabolic clearance of voriconazole in
      children versus adults.

PMID- 19841060
TI  - Contribution of the different UDP-glucuronosyltransferase (UGT) isoforms to
      buprenorphine and norbuprenorphine metabolism and relationship with the main UGT
      polymorphisms in a bank of human liver microsomes.
AB  - The goal of this study was to evaluate the specific contribution of individual
      UDP-glucuronosyltransferase (UGT) isoforms in the metabolism of buprenorphine
      (BUP) and norbuprenorphine (Nor-BUP), as well as the impact of their genetic
      variations. The glucuronidation of BUP and Nor-BUP was examined using human liver
      microsomes (HLMs) and heterologously expressed UGTs. The individual contribution
      of UGT isoforms was estimated using enzyme kinetic experiments combined with the
      relative activity factor (RAF). Phenotype-genotype relationships were
      investigated in a bank of 52 HLMs. Among the six hepatic UGT isoforms tested,
      UGT1A1, UGT1A3, and UGT2B7 metabolized BUP and Nor-BUP. Using the RAF approach,
      we found that UGT1A1 and UGT2B7 accounted for approximately 10 and 41% of BUP
      glucuronidation, respectively. Nor-BUP glucuronidation involved predominantly
      UGT1A3 (approximately 63%) and UGT1A1 (34%), whereas UGT2B7 had only a minor
      role. The UGT1A1 promoter (TA)(6/7)TAA mutation (UGT1A1*28) resulted in a 28%
      decrease of BUP glucuronidation V(max) in pooled HLMs but was not statistically
      associated with glucuronidation rate in 52 individual HLMs. The presence of the
      UGT2B7 promoter (G-842A) mutation resulted in higher BUP glucuronidation V(max)
      in pooled HLMs (+80% on average) and in a significant higher glucuronidation rate
      in noncarriers (but not in carriers) of the UGT1A1*28 allele (P = 0.0352). This
      study represents a functional basis for further clinical pharmacogenetic studies.

PMID- 19841061
TI  - Site-specific phosphorylation induces functionally active conformation in the
      intrinsically disordered N-terminal activation function (AF1) domain of the
      glucocorticoid receptor.
AB  - Intrinsically disordered (ID) regions are disproportionately higher in cell
      signaling proteins and are predicted to have much larger frequency of
      phosphorylation sites than ordered regions, suggesting an important role in their
      regulatory capacity. In this study, we show that AF1, an ID activation domain of
      the glucocorticoid receptor (GR), adopts a functionally folded conformation due
      to its site-specific phosphorylation by p38 mitogen-activated protein kinase,
      which is involved in apoptotic and gene-inductive events initiated by the GR.
      Further, we show that site-specific phosphorylation-induced secondary and
      tertiary structure formation specifically facilitates AF1's interaction with
      critical coregulatory proteins and subsequently its transcriptional activity.
      These data demonstrate a mechanism through which ID activation domain of the
      steroid receptors and other similar transcription factors may adopt a
      functionally active conformation under physiological conditions.

PMID- 19841062
TI  - Competition between the RNA transcript and the nontemplate DNA strand during R
      loop formation in vitro: a nick can serve as a strong R-loop initiation site.
AB  - Upon transcription of some sequences by RNA polymerases in vitro or in vivo, the
      RNA transcript can thread back onto the template DNA strand, resulting in an R
      loop. Previously, we showed that initiation of R-loop formation at an R-loop
      initiation zone (RIZ) is favored by G clusters. Here, using a purified in vitro
      system with T7 RNA polymerase, we show that increased distance between the
      promoter and the R-loop-supporting G-rich region reduces R-loop formation. When
      the G-rich portion of the RNA transcript is downstream from the 5' end of the
      transcript, the ability of this portion of the transcript to anneal to the
      template DNA strand is reduced. When we nucleolytically resect the beginning of
      the transcript, R-loop formation increases because the G-rich portion of the RNA
      is now closer to the 5' end of the transcript. Short G-clustered regions can act
      as RIZs and reduce the distance-induced suppression of R-loop formation.
      Supercoiled DNA is known to favor transient separation of the two DNA strands,
      and we find that this favors R-loop formation even in non-G-rich regions. Most
      strikingly, a nick can serve as a strong RIZ, even in regions with no G richness.
      This has important implications for class switch recombination and somatic
      hypermutation and possibly for other biological processes in transcribed regions.

PMID- 19841064
TI  - TFIIF facilitates dissociation of RNA polymerase II from noncoding RNAs that lack
      a repression domain.
AB  - Noncoding RNAs (ncRNAs) have recently been found to regulate multiple steps in
      mammalian mRNA transcription. Mouse B2 RNA and human Alu RNA bind RNA polymerase
      II (Pol II) and repress mRNA transcription, using regions of the ncRNAs referred
      to as repression domains. Two other ncRNAs, mouse B1 RNA and human small
      cytoplasmic Alu (scAlu) RNA, bind Pol II with high affinity but lack repression
      domains and hence do not inhibit transcription. To better understand the
      interplay between ncRNAs that bind Pol II and their functions in transcription,
      we studied how Pol II binding and transcriptional repression are controlled by
      general transcription factors. We found that TFIIF associates with B1 RNA/Pol II
      and scAlu RNA/Pol II complexes and decreases their kinetic stability. Both
      subunits of TFIIF are required for this activity. Importantly, fusing a
      repression domain to B1 RNA stabilizes its interaction with Pol II in the
      presence of TFIIF. These results suggest a new role for TFIIF in regulating the
      interaction of ncRNAs with Pol II; specifically, it destabilizes interactions
      with ncRNAs that are not transcriptional repressors. These studies also identify
      a new function for ncRNA repression domains: they stabilize interactions of
      ncRNAs with Pol II in the presence of TFIIF.

PMID- 19841063
TI  - Safeguarding entry into mitosis: the antephase checkpoint.
AB  - Maintenance of genomic stability is needed for cells to survive many rounds of
      division throughout their lifetime. Key to the proper inheritance of intact
      genome is the tight temporal and spatial coordination of cell cycle events.
      Moreover, checkpoints are present that function to monitor the proper execution
      of cell cycle processes. For instance, the DNA damage and spindle assembly
      checkpoints ensure genomic integrity by delaying cell cycle progression in the
      presence of DNA or spindle damage, respectively. A checkpoint that has recently
      been gaining attention is the antephase checkpoint that acts to prevent cells
      from entering mitosis in response to a range of stress agents. We review here
      what is known about the pathway that monitors the status of the cells at the
      brink of entry into mitosis when cells are exposed to insults that threaten the
      proper inheritance of chromosomes. We highlight issues which are unresolved in
      terms of our understanding of the antephase checkpoint and provide some
      perspectives on what lies ahead in the understanding of how the checkpoint
      functions.

PMID- 19841065
TI  - The role of Coa2 in hemylation of yeast Cox1 revealed by its genetic interaction
      with Cox10.
AB  - Saccharomyces cerevisiae cells lacking the cytochrome c oxidase (CcO) assembly
      factor Coa2 are impaired in Cox1 maturation and exhibit a rapid degradation of
      newly synthesized Cox1. The respiratory deficiency of coa2 Delta cells is
      suppressed either by the presence of a mutant allele of the Cox10 farnesyl
      transferase involved in heme a biosynthesis or through impaired proteolysis by
      the disruption of the mitochondrial Oma1 protease. Cox10 with an N196K
      substitution functions as a robust gain-of-function suppressor of the respiratory
      deficiency of coa2 Delta cells but lacks suppressor activity for two other CcO
      assembly mutant strains, the coa1 Delta and shy1 Delta mutants. The suppressor
      activity of N196K mutant Cox10 is dependent on its catalytic function and the
      presence of Cox15, the second enzyme involved in heme a biosynthesis. Varying the
      substitution at Asn196 reveals a correlation between the suppressor activity and
      the stabilization of the high-mass homo-oligomeric Cox10 complex. We postulate
      that the mutant Cox10 complex has enhanced efficiency in the addition of heme a
      to Cox1. Coa2 appears to impart stability to the oligomeric wild-type Cox10
      complex involved in Cox1 hemylation.

PMID- 19841066
TI  - Prostaglandin promotion of osteocyte gap junction function through
      transcriptional regulation of connexin 43 by glycogen synthase kinase 3/beta
      catenin signaling.
AB  - Gap junction intercellular communication in osteocytes plays an important role in
      bone remodeling in response to mechanical loading; however, the responsible
      molecular mechanisms remain largely unknown. Here, we show that phosphoinositide
      3 kinase (PI3K)/Akt signaling activated by fluid flow shear stress and
      prostaglandin E(2) (PGE(2)) had a stimulatory effect on both connexin 43 (Cx43)
      mRNA and protein expression. PGE(2) inactivated glycogen synthase kinase 3 (GSK
      3) and promoted nuclear localization and accumulation of beta-catenin. Knockdown
      of beta-catenin expression resulted in a reduction in Cx43 protein. Furthermore,
      the chromatin immunoprecipitation (ChIP) assay demonstrated an association of
      beta-catenin with the Cx43 promoter, suggesting that beta-catenin could regulate
      Cx43 expression at the level of gene transcription. We have previously reported
      that PGE(2) activates cyclic AMP (cAMP)-protein kinase A (PKA) signaling and
      increases Cx43 and gap junctions. Interestingly, the activation of PI3K/Akt
      appeared to be independent of the activation of PKA, whereas both PI3K/Akt and
      PKA signaling inactivated GSK-3 and increased beta-catenin translocation.
      Together, these results suggest that shear stress, through PGE(2) release,
      activates both PI3K/Akt and cAMP-PKA signaling, which converge through the
      inactivation of GSK-3, leading to the increase in nuclear accumulation of beta
      catenin. beta-Catenin binds to the Cx43 promoter, stimulating Cx43 expression and
      functional gap junctions between osteocytes.

PMID- 19841067
TI  - Functional cooperation of the proapoptotic Bcl2 family proteins Bmf and Bim in
      vivo.
AB  - Bcl2-modifying factor (Bmf) is a member of the BH3-only group of proapoptotic
      proteins. To test the role of Bmf in vivo, we constructed mice with a series of
      mutated Bmf alleles that disrupt Bmf expression, prevent Bmf phosphorylation by
      the c-Jun NH(2)-terminal kinase (JNK) on Ser(74), or mimic Bmf phosphorylation on
      Ser(74). We report that the loss of Bmf causes defects in uterovaginal
      development, including an imperforate vagina and hydrometrocolpos. We also show
      that the phosphorylation of Bmf on Ser(74) can contribute to a moderate increase
      in levels of Bmf activity. Studies of compound mutants with the related gene Bim
      demonstrated that Bim and Bmf exhibit partially redundant functions in vivo.
      Thus, developmental ablation of interdigital webbing on mouse paws and normal
      lymphocyte homeostasis require the cooperative activity of Bim and Bmf.

PMID- 19841068
TI  - TLS inhibits RNA polymerase III transcription.
AB  - RNA transcription by all the three RNA polymerases (RNAPs) is tightly controlled,
      and loss of regulation can lead to, for example, cellular transformation and
      cancer. While most transcription factors act specifically with one polymerase, a
      small number have been shown to affect more than one polymerase to coordinate
      overall levels of transcription in cells. Here we show that TLS (translocated in
      liposarcoma), a protein originally identified as the product of a chromosomal
      translocation and which associates with both RNAP II and the spliceosome, also
      represses transcription by RNAP III. TLS was found to repress transcription from
      all three classes of RNAP III promoters in vitro and to associate with RNAP III
      genes in vivo, perhaps via a direct interaction with the pan-specific
      transcription factor TATA-binding protein (TBP). Depletion of TLS by small
      interfering RNA (siRNA) in HeLa cells resulted in increased steady-state levels
      of RNAP III transcripts as well as increased RNAP III and TBP occupancy at RNAP
      III-transcribed genes. Conversely, overexpression of TLS decreased accumulation
      of RNAP III transcripts. These unexpected findings indicate that TLS regulates
      both RNAPs II and III and supports the possibility that cross-regulation between
      RNA polymerases is important in maintaining normal cell growth.

PMID- 19841069
TI  - Role of muscle c-Jun NH2-terminal kinase 1 in obesity-induced insulin resistance.
AB  - Obesity caused by feeding of a high-fat diet (HFD) is associated with an
      increased activation of c-Jun NH(2)-terminal kinase 1 (JNK1). Activated JNK1 is
      implicated in the mechanism of obesity-induced insulin resistance and the
      development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1(-)(/)(
      ) mice are protected against HFD-induced obesity and insulin resistance. Here we
      show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD
      induced obesity. However, muscle-specific JNK1-deficient (M(KO)) mice exhibit
      improved insulin sensitivity compared with control wild-type (M(WT)) mice. Thus,
      insulin-stimulated AKT activation is suppressed in muscle, liver, and adipose
      tissue of HFD-fed M(WT) mice but is suppressed only in the liver and adipose
      tissue of M(KO) mice. These data demonstrate that JNK1 in muscle contributes to
      peripheral insulin resistance in response to diet-induced obesity.

PMID- 19841070
TI  - A role for VAMP8/endobrevin in surface deployment of the water channel aquaporin
      2.
AB  - Vesicle-associated-membrane protein 8 (VAMP8) is highly expressed in the kidney,
      but the exact physiological and molecular functions executed by this v-SNARE
      protein in nephrons remain elusive. Here, we show that the depletion of VAMP8 in
      mice resulted in hydronephrosis. Furthermore, the level of the vasopressin
      responsive water channel aquaporin 2 (AQP2) was increased by three- to fivefold
      in VAMP8-null mice. Forskolin and [desamino-Cys(1), D-Arg(8)]-vasopressin (DDAVP)
      induced AQP2 exocytosis was impaired in VAMP8-null collecting duct cells. VAMP8
      was revealed to colocalize with AQP2 on intracellular vesicles and to interact
      with the plasma membrane t-SNARE proteins syntaxin4 and syntaxin3, suggesting
      that VAMP8 mediates the regulated fusion of AQP2-positive vesicles with the
      plasma membrane.

PMID- 19841071
TI  - Effect of MarA-like proteins on antibiotic resistance and virulence in Yersinia
      pestis.
AB  - MarA, an AraC/XylS transcriptional regulator in Escherichia coli, affects drug
      susceptibility and virulence. Two MarA-like proteins have been found in Yersinia
      pestis: MarA47 and MarA48. Deletion or overexpression of these proteins in the
      attenuated KIM 1001 Deltapgm strain led to a change in multidrug susceptibility
      (including susceptibility to clinically relevant drugs). Additionally, lung
      colonization by the marA47 or marA48 deletion mutant was decreased about 10-fold
      in a pneumonic plague mouse model. Complementation of the deletions by replacing
      the deleted genes on the chromosome restored wild-type characteristics. These
      findings show that two MarA homologs in Y. pestis affect antibiotic
      susceptibility and virulence.

PMID- 19841072
TI  - Helicobacter pylori promotes the production of thymic stromal lymphopoietin by
      gastric epithelial cells and induces dendritic cell-mediated inflammatory Th2
      responses.
AB  - Helicobacter pylori colonizes the stomach and induces strong, specific local and
      systemic humoral and cell-mediated immunity, resulting in the development of
      chronic gastritis in humans. Although H. pylori-induced chronic atrophic
      gastritis is characterized by marked infiltration of T helper type 1 (Th1)
      cytokine-producing CD4(+) T cells, almost all of the inflamed gastric mucosae
      also contain focal lymphoid aggregates with germinal centers. In addition,
      typical H. pylori-induced chronic gastritis in children, called follicular
      gastritis, is characterized by B-cell follicle formation in the gastric mucosa.
      The aim of this study was to examine whether thymic stromal lymphopoietin (TSLP),
      an epithelial-cell-derived cytokine inducing a dendritic cell (DC)-mediated
      inflammatory Th2 response, is involved in Th2 responses triggering B-cell
      activation in H. pylori-induced gastritis. Here, we show that H. pylori triggered
      human gastric epithelial cells to produce TSLP, together with the DC-attracting
      chemokine MIP-3alpha and the B-cell-activating factor BAFF. After DCs were
      incubated with supernatants from H. pylori-infected epithelial cells, the
      conditioned cells expressed high levels of costimulatory molecules, such as CD80,
      and triggered naive CD4(+) T cells to produce high levels of the Th2 cytokines
      interleukin-4 and interleukin-13 and of the inflammatory cytokines tumor necrosis
      factor alpha and gamma interferon. In contrast, after incubation of the
      supernatants with the neutralizing antibodies to TSLP, the conditioned DCs did
      not prime T cells to produce high levels of Th2 cytokines. These results,
      together with the finding that TSLP was expressed by the epithelial cells of
      human follicular gastritis, suggest that H. pylori can directly trigger
      epithelial cells to produce TSLP. It also suggests that TSLP-mediated DC
      activation may be involved in Th2 responses triggering B-cell activation in H.
      pylori-induced gastritis.

PMID- 19841073
TI  - Host chemokine and cytokine response in the endocervix within the first
      developmental cycle of Chlamydia muridarum.
AB  - The initial host response in a primary chlamydial infection is the onset of acute
      inflammation. However, we still know very little about the early temporal events
      in the induction of the acute inflammatory response and how these events relate
      to the initial chlamydial developmental cycle in an actual genital infection.
      Because it was critical to initiate a synchronous infection in the endocervix in
      the first 24 h to evaluate the sequential expression of the host response, we
      developed the surgical methodology of depositing Chlamydia muridarum directly on
      the endocervix. Cervical tissue was collected at 3, 12, and 24 h after
      inoculation and the expression array of chemokines, cytokines, and receptors was
      assessed to characterize the response during the initial developmental cycle.
      Polymorphonuclear leukocyte (PMN) infiltration was first observed at 12 h after
      inoculation, and a few PMNs could be seen in the epithelium at 24 h. Electron
      microscopic analysis at 24 h showed that virtually all inclusions were at the
      same stage of development, indicating a synchronous infection. Several chemokine
      and cytokine genes were expressed as early as 3 h after infection, but by 12 h,
      41 genes were expressed. Thus, activation of the host response occurs both with
      the introduction of elementary bodies into the host and early replication of
      reticulate bodies. No significant response was observed when UV-inactivated
      organisms were inoculated into the cervix at any time interval. This model
      provides an ideal opportunity to investigate the mechanisms by which the early
      inflammatory response is induced in vivo.

PMID- 19841074
TI  - The presence of CD14 overcomes evasion of innate immune responses by virulent
      Francisella tularensis in human dendritic cells in vitro and pulmonary cells in
      vivo.
AB  - Francisella tularensis is a Gram-negative bacterium that causes acute, lethal
      disease following inhalation. We have previously shown that viable F. tularensis
      fails to stimulate secretion of proinflammatory cytokines following infection of
      human dendritic cells (hDC) in vitro and pulmonary cells in vivo. Here we
      demonstrate that the presence of the CD14 receptor is critical for detection of
      virulent F. tularensis strain SchuS4 by dendritic cells, monocytes, and pulmonary
      cells. Addition of soluble CD14 (sCD14) to hDC restored cytokine production
      following infection with strain SchuS4. In contrast, addition of anti-CD14 to
      monocyte cultures inhibited the ability of these cells to respond to strain
      SchuS4. Addition of CD14 or blocking CD14 following SchuS4 infection in dendritic
      cells and monocytes, respectively, was not due to alterations in phagocytosis or
      replication of the bacterium in these cells. Administration of sCD14 in vivo also
      restored cytokine production following infection with strain SchuS4, as assessed
      by increased concentrations of tumor necrosis factor alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), IL-12p70, and IL-6 in the lungs of mice receiving
      sCD14 compared to mock-treated controls. In contrast to homogenous cultures of
      monocytes or dendritic cells infected in vitro, mice treated with sCD14 in vivo
      also exhibited controlled bacterial replication and dissemination compared to
      mock-treated controls. Interestingly, animals that lacked CD14 were not more
      susceptible or resistant to pulmonary infection with SchuS4. Together, these data
      support the hypothesis that the absence or low abundance of CD14 on hDC and in
      the lung contributes to evasion of innate immunity by virulent F. tularensis.
      However, CD14 is not required for development of inflammation during the last 24
      to 48 h of SchuS4 infection. Thus, the presence of this receptor may aid in
      control of virulent F. tularensis infections at early, but not late, stages of
      infection.

PMID- 19841075
TI  - Mouse macrophages are permissive to motile Legionella species that fail to
      trigger pyroptosis.
AB  - Legionella pneumophila, a motile opportunistic pathogen of humans, is restricted
      from replicating in the lungs of C57BL/6 mice. Resistance of mouse macrophages to
      L. pneumophila depends on recognition of cytosolic flagellin. Once detected by
      the NOD-like receptors Naip5 and Ipaf (Nlrc4), flagellin triggers pyroptosis, a
      proinflammatory cell death. In contrast, motile strains of L. parisiensis and L.
      tucsonensis replicate profusely within C57BL/6 macrophages, similar to flagellin
      deficient L. pneumophila. To gain insight into how motile species escape innate
      defense mechanisms of mice, we compared their impacts on macrophages. L.
      parisiensis and L. tucsonensis do not induce proinflammatory cell death, as
      measured by lactate dehydrogenase (LDH) release and interleukin-1beta (IL-1beta)
      secretion. However, flagellin isolated from L. parisiensis and L. tucsonensis
      triggers cell death and IL-1beta secretion when transfected into the cytosol of
      macrophages. Neither strain displays three characteristics of the canonical L.
      pneumophila Dot/Icm type IV secretion system: sodium sensitivity, LAMP-1 evasion,
      and pore formation. Therefore, we postulate that when L. parisiensis and L.
      tucsonensis invade a mouse macrophage, flagellin is confined to the phagosome,
      protecting the bacteria from recognition by the cytosolic surveillance system and
      allowing Legionella to replicate. Despite their superior capacity to multiply in
      mouse macrophages, L. parisiensis and L. tucsonensis have been associated with
      only two cases of disease, both in renal transplant patients. These results point
      to the complexity of disease, a product of the pathogenic potential of the
      microbe, as defined in the laboratory, and the capacity of the host to mount a
      measured defense.

PMID- 19841076
TI  - CcpA and LacD.1 affect temporal regulation of Streptococcus pyogenes virulence
      genes.
AB  - Production of H(2)O(2) follows a growth phase-dependent pattern that mimics that
      of many virulence factors of Streptococcus pyogenes. To gain greater insight into
      mechanisms coupling virulence factor expression to growth phase, we investigated
      the molecular basis for H(2)O(2) generation and its regulation. Deletion of the
      gene encoding lactate oxidase (lctO) or culture in the presence of glucose
      eliminated H(2)O(2) production, implicating carbohydrate regulation of lctO as a
      key element of growth phase control. In examining known carbohydrate-responsive
      regulators, deletion of the gene encoding CcpA but not that encoding LacD.1
      resulted in both derepression and an uncoupling of lctO transcription from its
      growth phase pattern. Expanding this analysis to additional virulence factors
      demonstrated both negative (cfa, encoding CAMP factor) and positive (speB,
      encoding a cysteine protease) regulation by CcpA and that CcpA mutants were
      highly cytotoxic for cultured macrophages. This latter property resulted from
      enhanced transcription of the streptolysin S biogenesis operon. Examination of
      CcpA-promoter interactions using a DNA pull-down assay mimicking physiological
      conditions showed direct binding to the promoters of lctO and speB but not those
      of sagA. CcpA but not LacD.1 mutants were attenuated in a murine model of soft
      tissue infection, and analysis of gene expression in infected tissue indicated
      that CcpA mutants had altered expression of lctO, cfa, and speB but not the
      indirectly regulated sagA gene. Taken together, these data show that CcpA
      regulates virulence genes via at least three distinct mechanisms and that
      disruption of growth phase regulation alters transcriptional patterns in infected
      tissues.

PMID- 19841077
TI  - Absence of inflammation and pneumonia during infection with nonpigmented Yersinia
      pestis reveals a new role for the pgm locus in pathogenesis.
AB  - Yersinia pestis causes primary pneumonic plague in many mammalian species,
      including humans, mice, and rats. Virulent Y. pestis strains undergo frequent
      spontaneous deletion of a 102-kb chromosomal DNA fragment, known as the
      pigmentation (pgm) locus, when grown in laboratory media, yet this locus is
      present in every virulent isolate. The pgm locus encodes, within a high
      pathogenicity island, siderophore biosynthesis genes that are required for growth
      in the mammalian host when inoculated by peripheral routes. Recently, higher
      challenge doses of nonpigmented Y. pestis were reported to cause fatal pneumonic
      plague in mice, suggesting a useful model for studies of virulence and immunity.
      In this work, we show that intranasal infection of BALB/c mice with nonpigmented
      Yersinia pestis does not result in pneumonic plague. Despite persistent bacterial
      colonization of the lungs and the eventual death of infected mice, pulmonary
      inflammation was generally absent, and there was no disease pathology
      characteristic of pneumonic plague. Iron given to mice at the time of challenge,
      previously shown to enhance the virulence of pgm-deficient strains, resulted in
      an accelerated disease course, with less time to bacteremia and lethality, but
      lung inflammation and pneumonia were still absent. We examined other rodent
      models and found differences in lung inflammatory responses, some of which led to
      clearance and survival even when high challenge doses were used. Together, the
      results suggest that the Y. pestis pgm locus encodes previously unappreciated
      virulence factors required for the induction of pneumonic plague that are
      independent of iron scavenging from the mammalian host.

PMID- 19841078
TI  - Requirement for formin-induced actin polymerization during spread of Shigella
      flexneri.
AB  - Actin polymerization in the cytosol and at the plasma membrane is locally
      regulated by actin nucleators. Several microbial pathogens exploit cellular actin
      polymerization to spread through tissue. The movement of the enteric pathogen
      Shigella flexneri, both within the cell body and from cell to cell, depends on
      actin polymerization. During intercellular spread, actin polymerization at the
      bacterial surface generates protrusions of the plasma membrane, which are
      engulfed by adjacent cells. In the cell body, polymerization of actin by Shigella
      spp. is dependent on N-WASP activation of the Arp2/Arp3 complex. Here we
      demonstrate that, in contrast, efficient protrusion formation and intercellular
      spread depend on actin polymerization that involves activation of the Diaphanous
      formin Dia. While the Shigella virulence protein IpgB2 can bind and activate Dia1
      (N. M. Alto et al., Cell 124:133-145, 2006), its absence does not result in a
      detectable defect in Dia-dependent protrusion formation or spread. The dependence
      on the activation of Dia during S. flexneri infection contrasts with the
      inhibition of this pathway observed during vaccinia virus infection.

PMID- 19841079
TI  - Mycobacterium leprae actively modulates the cytokine response in naive human
      monocytes.
AB  - Leprosy is a chronic but treatable infectious disease caused by the intracellular
      pathogen Mycobacterium leprae. Host immunity to M. leprae determines the
      diversity of clinical manifestations seen in patients, from tuberculoid leprosy
      with robust production of Th1-type cytokines to lepromatous disease,
      characterized by elevated levels of Th2-type cytokines and a suboptimal
      proinflammatory response. Previous reports have indicated that M. leprae is a
      poor activator of macrophages and dendritic cells in vitro. To understand whether
      M. leprae fails to elicit an optimal Th1 immune response or actively interferes
      with its induction, we have examined the early interactions between M. leprae and
      monocytes from healthy human donors. We found that, in naive monocytes, M. leprae
      induced high levels of the negative regulatory molecules MCP-1 and interleukin-1
      (IL-1) receptor antagonist (IL-1Ra), while suppressing IL-6 production through
      phosphoinositide-3 kinase (PI3K)-dependent mechanisms. In addition, low levels of
      proinflammatory cytokines were observed in association with reduced activation of
      nuclear factor-kappaB (NF-kappaB) and delayed activation of IL-1beta-converting
      enzyme, ICE (caspase-1), in monocytes stimulated with M. leprae compared with
      Mycobacterium bovis BCG stimulation. Interestingly, although in itself a weak
      stimulator of cytokines, M. leprae primed the cells for increased production of
      tumor necrosis factor alpha and IL-10 in response to a strongly inducing
      secondary stimulus. Taken together, our results suggest that M. leprae plays an
      active role to control the release of cytokines from monocytes by providing both
      positive and negative regulatory signals via multiple signaling pathways
      involving PI3K, NF-kappaB, and caspase-1.

PMID- 19841080
TI  - Localization and developmental regulation of a dispersed gene family 1 protein in
      Trypanosoma cruzi.
AB  - The dispersed gene family 1 (DGF-1) is the fifth largest gene family in the
      Trypanosoma cruzi genome, with over 500 members (11). Many of the predicted DGF-1
      protein products have several transmembrane domains and N-glycosylation and
      phosphorylation sites and were thought to localize in the plasma membrane. Here,
      we report that affinity-purified antibodies against a region of one of these
      proteins (DGF-1.2) localized it intracellularly in different stages of the
      parasite. DGF-1.2 is more abundant in the amastigote stage than in
      trypomastigotes and epimastigotes, as detected by immunofluorescence and Western
      blot analyses. The protein changed localization during intracellular or
      extracellular differentiation from the trypomastigote to the amastigote stage,
      where it finally localized to small bodies in close contact with the inner side
      of the amastigote plasma membrane. DGF-1.2 did not colocalize with markers of
      other subcellular organelles, such as acidocalcisomes, glycosomes, reservosomes,
      lipid droplets, or endocytic vesicles. During extracellular differentiation, the
      protein was detected in the culture medium from 0 to 22 h, peaking at 14 h. The
      presence of DGF-1.2 in the differentiation culture medium was confirmed by mass
      spectrometry analysis. Finally, when epimastigotes were subjected to starvation,
      there was a decrease in the labeling of the cells and, in Western blots, the
      appearance of bands of lower molecular mass, suggesting its cleavage. These
      results represent the first report of direct immunodetection and developmental
      expression and secretion of a DGF-1 protein.

PMID- 19841081
TI  - Characterization of novel beta-galactosidase activity that contributes to
      glycoprotein degradation and virulence in Streptococcus pneumoniae.
AB  - The pneumococcus obtains its energy from the metabolism of host glycosides.
      Therefore, efficient degradation of host glycoproteins is integral to
      pneumococcal virulence. In search of novel pneumococcal glycosidases, we
      characterized the Streptococcus pneumoniae strain D39 protein encoded by SPD_0065
      and found that this gene encodes a beta-galactosidase. The SPD_0065 recombinant
      protein released galactose from desialylated fetuin, which was used here as a
      model of glycoproteins found in vivo. A pneumococcal mutant with a mutation in
      SPD_0065 showed diminished beta-galactosidase activity, exhibited an extended lag
      period in mucin-containing defined medium, and cleaved significantly less
      galactose than the parental strain during growth on mucin. As pneumococcal beta
      galactosidase activity had been previously attributed solely to SPD_0562 (bgaA),
      we evaluated the contribution of SPD_0065 and SPD_0562 to total beta
      galactosidase activity. Mutation of either gene significantly reduced enzymatic
      activity, but beta-galactosidase activity in the double mutant, although
      significantly less than that in either of the single mutants, was not completely
      abolished. The expression of SPD_0065 in S. pneumoniae grown in mucin-containing
      medium or tissues harvested from infected animals was significantly upregulated
      compared to that in pneumococci from glucose-containing medium. The SPD_0065
      mutant strain was found to be attenuated in virulence in a manner specific to the
      host tissue.

PMID- 19841082
TI  - Roles of capsule and lipopolysaccharide O antigen in interactions of human
      monocyte-derived dendritic cells and Klebsiella pneumoniae.
AB  - In humans, Klebsiella pneumoniae is a saprophytic bacterium of the nasopharyngeal
      and intestinal mucosae that is also frequently responsible for severe nosocomial
      infections. Two major factors of virulence, capsular polysaccharide (CPS) and
      lipopolysaccharide (LPS) O antigen, are involved in mucosal colonization and the
      development of infections. These bacterial surface structures are likely to play
      major roles in interactions with the mucosal immune system, which are
      orchestrated by a network of surveillance based on dendritic cells (DCs). To
      determine the roles of K. pneumoniae CPS and LPS in the DC response, we
      investigated the response of immature human monocyte-derived DCs to bacterial
      challenge with a wild-type strain and its isogenic mutants deficient in CPS or
      LPS O-antigen production. As observed by flow cytometry and confocal laser
      microscopy, the rate of phagocytosis was inversely proportional to the amount of
      CPS on the bacterial cell surface, with LPS playing little or no role. The K.
      pneumoniae wild-type strain induced DC maturation with upregulation of CD83,
      CD86, and TLR4 and downregulation of CD14 and DC-SIGN. With CPS mutants, we
      observed a greater decrease in DC-SIGN, suggesting a superior maturation of DCs.
      In addition, incubation of DCs with CPS mutants, and to a lesser extent with LPS
      mutants, resulted in significantly higher Th1 cytokine production. Combined, our
      findings suggest that K. pneumoniae CPS, by hampering bacterial binding and
      internalization, induces a defective immunological host response, including
      maturation of DCs and pro-Th1 cytokine production, whereas the LPS O antigen
      seems to be involved essentially in DC activation.

PMID- 19841083
TI  - Mannose receptor-dependent delay in phagosome maturation by Mycobacterium avium
      glycopeptidolipids.
AB  - The ability of pathogenic mycobacteria to block phagosome-lysosome fusion is
      critical for its pathogenesis. The molecules expressed by mycobacteria that
      inhibit phagosome maturation and the mechanism of this inhibition have been
      extensively studied. Recent work has indicated that mannosylated
      lipoarabinomannan (ManLAM) isolated from Mycobacterium tuberculosis can function
      to delay phagosome-lysosome fusion and that this delay requires the interaction
      of ManLAM with the mannose receptor (MR). However, the molecules expressed by
      other pathogenic mycobacteria that function to inhibit phagosome maturation have
      not been well described. In the present study, we show that phagosomes containing
      silica beads coated with glycopeptidolipids (GPLs), a major surface component of
      Mycobacterium avium, showed limited acidification and delayed recruitment of late
      endosomal/lysosomal markers compared to those of phosphatidylcholine-coated
      beads. The carbohydrate component of the GPLs was required, as beads coated only
      with the lipopeptide core failed to delay phagosome-lysosome fusion. Moreover,
      the ability of GPLs to delay phagosome maturation was dependent on the macrophage
      expression of the MR. Using CHO cells expressing the MR, we confirmed that the
      GPLs bind this receptor. Finally, human monocyte-derived macrophages knocked down
      for MR expression showed increased M. avium phagosome-lysosome fusion relative to
      control cells. Together, the data indicate that GPLs can function to delay
      phagosome-lysosome fusion and suggest that GPLs, like ManLAM, work through the MR
      to mediate this activity.

PMID- 19841085
TI  - Prospective identification, isolation, and systemic transplantation of
      multipotent mesenchymal stem cells in murine bone marrow.
AB  - Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in
      vitro growth and can give rise to multiple mesenchymal lineages. Because MSCs
      have only been isolated from tissue in culture, the equivalent cells have not
      been identified in vivo and little is known about their physiological roles or
      even their exact tissue location. In this study, we used phenotypic,
      morphological, and functional criteria to identify and prospectively isolate a
      subset of MSCs (PDGFRalpha+Sca-1+CD45-TER119-) from adult mouse bone marrow.
      Individual MSCs generated colonies at a high frequency and could differentiate
      into hematopoietic niche cells, osteoblasts, and adipocytes after in vivo
      transplantation. Naive MSCs resided in the perivascular region in a quiescent
      state. This study provides the useful method needed to identify MSCs as defined
      in vivo entities.

PMID- 19841086
TI  - A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune
      disease versus autoimmune reactivity.
AB  - ZAP-70 is critical for T cell receptor (TCR) signaling. Tyrosine to phenylalanine
      mutations of Y315 and Y319 in ZAP-70 suggest these residues function to recruit
      downstream effector molecules, but mutagenesis and crystallization studies reveal
      that these residues also play an important role in autoinhibition ZAP-70. To
      address the importance of the scaffolding function, we generated a zap70 mutant
      mouse (YYAA mouse) with Y315 and Y319 both mutated to alanines. These YYAA mice
      reveal that the scaffolding function is important for normal development and
      function. Moreover, the YYAA mice have many similarities to a previously
      identified ZAP-70 mutant mouse, SKG, which harbors a distinct hypomorphic
      mutation. Both YYAA and SKG mice have impaired T cell development and
      hyporesponsiveness to TCR stimulation, markedly reduced numbers of thymic T
      regulatory cells and defective positive and negative selection. YYAA mice, like
      SKG mice, develop rheumatoid factor antibodies, but fail to develop autoimmune
      arthritis. Signaling differences that result from ZAP-70 mutations appear to skew
      the TCR repertoire in ways that differentially influence propensity to
      autoimmunity versus autoimmune disease susceptibility. By uncoupling the relative
      contribution from T regulatory cells and TCR repertoire during thymic selection,
      our data help to identify events that may be important, but alone are
      insufficient, for the development of autoimmune disease.

PMID- 19841087
TI  - Dependence of proliferative vascular smooth muscle cells on CD98hc (4F2hc,
      SLC3A2).
AB  - Activation of vascular smooth muscle cells (VSMCs) to migrate and proliferate is
      essential for the formation of intimal hyperplasia. Hence, selectively targeting
      activated VSMCs is a potential strategy against vaso-occlusive disorders such as
      in-stent restenosis, vein-graft stenosis, and transplant vasculopathy. We show
      that CD98 heavy chain (CD98hc) is markedly up-regulated in neointimal and
      cultured VSMCs, and that activated but not quiescent VSMCs require CD98hc for
      survival. CD98hc mediates integrin signaling and localizes amino acid
      transporters to the plasma membrane. SMC-specific deletion of CD98hc did not
      affect normal vessel morphology, indicating that CD98hc was not required for the
      maintenance of resident quiescent VSMCs; however, CD98hc deletion reduced intimal
      hyperplasia after arterial injury. Ex vivo and in vitro, loss of CD98hc
      suppressed proliferation and induced apoptosis in VSMCs. Furthermore,
      reconstitution with CD98hc mutants showed that CD98hc interaction with integrins
      was necessary for the survival of VSMCs. These studies establish the importance
      of CD98hc in VSMC proliferation and survival. Furthermore, loss of CD98hc was
      selectively deleterious to activated VSMCs while sparing resident quiescent
      VSMCs, suggesting that activated VSMCs are physiologically dependent on CD98hc,
      and hence, CD98hc is a potential therapeutic target in vaso-occlusive disorders.

PMID- 19841088
TI  - Masking MALT1: the paracaspase's potential for cancer therapy.
AB  - A key feature of aggressive B cell lymphomas is constitutive NF-kappaB
      activation, which requires signals from the CARD11-BCL-10-MALT1 (CMB) complex.
      The unique enzymatic activity of MALT1 degrades one of its binding partners, BCL
      10, as well as the NF-kappaB inhibitor A20. New data shows that targeting MALT1
      protease activity may be a promising therapeutic strategy for treating aggressive
      B cell lymphomas.

PMID- 19841089
TI  - Inhibition of MALT1 protease activity is selectively toxic for activated B cell
      like diffuse large B cell lymphoma cells.
AB  - Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoma in
      humans. The aggressive activated B cell-like (ABC) subtype of DLBCL is
      characterized by constitutive NF-kappaB activity and requires signals from
      CARD11, BCL10, and the paracaspase MALT1 for survival. CARD11, BCL10, and MALT1
      are scaffold proteins that normally associate upon antigen receptor ligation.
      Signal-induced CARD11-BCL10-MALT1 (CBM) complexes couple upstream events to
      IkappaB kinase (IKK)/NF-kappaB activation. MALT1 also possesses a recently
      recognized proteolytic activity that cleaves and inactivates the negative NF
      kappaB regulator A20 and BCL10 upon antigen receptor ligation. Yet, the relevance
      of MALT1 proteolytic activity for malignant cell growth is unknown. Here, we
      demonstrate preassembled CBM complexes and constitutive proteolysis of the two
      known MALT1 substrates in ABC-DLBCL, but not in germinal center B cell-like (GCB)
      DLBCL. ABC-DLBCL cell treatment with a MALT1 protease inhibitor blocks A20 and
      BCL10 cleavage, reduces NF-kappaB activity, and decreases the expression of NF
      kappaB targets genes. Finally, MALT1 paracaspase inhibition results in death and
      growth retardation selectively in ABC-DLBCL cells. Thus, our results indicate a
      growth-promoting role for MALT1 paracaspase activity in ABC-DLBCL and suggest
      that a pharmacological MALT1 protease inhibition could be a promising approach
      for lymphoma treatment.

PMID- 19841090
TI  - Runx proteins regulate Foxp3 expression.
AB  - Runx proteins are essential for hematopoiesis and play an important role in T
      cell development by regulating key target genes, such as CD4 and CD8 as well as
      lymphokine genes, during the specialization of naive CD4 T cells into distinct T
      helper subsets. In regulatory T (T reg) cells, the signature transcription factor
      Foxp3 interacts with and modulates the function of several other DNA binding
      proteins, including Runx family members, at the protein level. We show that Runx
      proteins also regulate the initiation and the maintenance of Foxp3 gene
      expression in CD4 T cells. Full-length Runx promoted the de novo expression of
      Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant
      negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3
      expression in natural T reg cells remained dependent on Runx proteins and
      correlated with the binding of Runx/core-binding factor beta to regulatory
      elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components
      of a feed-forward loop in which Runx proteins contribute to the expression of
      Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream
      target genes.

PMID- 19841091
TI  - Snf1p regulates Gcn5p transcriptional activity by antagonizing Spt3p.
AB  - The budding yeast Gcn5p is a prototypic histone acetyltransferase controlling
      transcription of diverse genes. Here we show that Gcn5p is itself regulated by
      Snf1p and Spt3p. Snf1p likely controls Gcn5p via direct interaction. Mutating
      four residues in the Gcn5p catalytic domain, T203, S204, T211, and Y212 (TSTY),
      phenocopies snf1 null cells, including Gcn5p hypophosphorylation, hypoacetylation
      at the HIS3 promoter, and transcriptional defects of the HIS3 gene. However,
      overexpressing Snf1p suppresses the above phenotypes associated with the
      phosphodeficient TSTY mutant, suggesting that it is the interaction with Snf1p
      important for Gcn5p to activate HIS3. A likely mechanism by which Snf1p
      potentiates Gcn5p function is to antagonize Spt3p, because the HIS3 expression
      defects caused by snf1 knockout, or by the TSTY gcn5 mutations, can be suppressed
      by deleting SPT3. In vitro, Spt3p binds Gcn5p, but the interaction is drastically
      enhanced by the TSTY mutations, indicating that a stabilized Spt3p-Gcn5p
      interaction may be an underlying cause for the aforementioned HIS3
      transcriptional defects. These results suggest that Gcn5p is a target regulated
      by the competing actions of Snf1p and Spt3p.

PMID- 19841092
TI  - Drosophila translational elongation factor-1gamma is modified in response to DOA
      kinase activity and is essential for cellular viability.
AB  - Drosophila translational elongation factor-1gamma (EF1gamma) interacts in the
      yeast two-hybrid system with DOA, the LAMMER protein kinase of Drosophila.
      Analysis of mutant EF1gamma alleles reveals that the locus encodes a structurally
      conserved protein essential for both organismal and cellular survival. Although
      no genetic interactions were detected in combinations with mutations in EF1alpha,
      an EF1gamma allele enhanced mutant phenotypes of Doa alleles. A predicted LAMMER
      kinase phosphorylation site conserved near the C terminus of all EF1gamma
      orthologs is a phosphorylation site in vitro for both Drosophila DOA and tobacco
      PK12 LAMMER kinases. EF1gamma protein derived from Doa mutant flies migrates with
      altered mobility on SDS gels, consistent with it being an in vivo substrate of
      DOA kinase. However, the aberrant mobility appears to be due to a secondary
      protein modification, since the mobility of EF1gamma protein obtained from wild
      type Drosophila is unaltered following treatment with several nonspecific
      phosphatases. Expression of a construct expressing a serine-to-alanine
      substitution in the LAMMER kinase phosphorylation site into the fly germline
      rescued null EF1gamma alleles but at reduced efficiency compared to a wild-type
      construct. Our data suggest that EF1gamma functions in vital cellular processes
      in addition to translational elongation and is a LAMMER kinase substrate in vivo.

PMID- 19841093
TI  - Molecular characterization of the key switch F provides a basis for understanding
      the rapid divergence of the sex-determining pathway in the housefly.
AB  - The housefly, Musca domestica, is an excellent model system to study the
      diversification of the pathway that specifies the sexual fate. A number of
      different mechanisms have been described in the housefly, which reflects in part
      the broad diversity of sex-determining strategies used in insects. In this study
      we present the molecular identification and characterization of F, which acts as
      the master switch in the housefly pathway. We provide evidence that F corresponds
      to the transformer ortholog in Musca (Mdtra), which, as a result of alternative
      processing, expresses functional products only in individuals committed to the
      female fate. We demonstrate that, once activated, a self-sustaining feedback loop
      will maintain the female-promoting functions of Mdtra. Absence of Mdtra
      transcripts in eggs of Arrhenogenic (Ag) mutant females suggests that maternally
      deployed Mdtra activity initiates this self-sustaining loop in the zygote. When
      an M factor is paternally transmitted to the zygote, the establishment of the
      loop is prevented at an early stage before cellularization and splicing of Mdtra
      shifts irreversibly to the male nonproductive mode. On the basis of the analysis
      of two mutant alleles we can explain the different sex-determining systems in the
      housefly largely as deviations at the level of Mdtra regulation. This plasticity
      in the housefly pathway may provide a suitable framework to understand the
      evolution of sex-determining mechanisms in other insect species. For instance,
      while sex determination in a close relative, the tsetse fly Glossina morsitans,
      differs at the level of the instructive signal, we find that its tra ortholog,
      Gmtra, is regulated in a mode similar to that of Mdtra.

PMID- 19841094
TI  - DNA packaging by lambda-like bacteriophages: mutations broadening the packaging
      specificity of terminase, the lambda-packaging enzyme.
AB  - The DNA-packaging specificities of phages lambda and 21 depend on the specific
      DNA interactions of the small terminase subunits, which have support helix-turn
      recognition helix-wing DNA-binding motifs. lambda-Terminase with the recognition
      helix of 21 preferentially packages 21 DNA. This chimeric terminase's ability to
      package lambdaDNA is reduced approximately 20-fold. Phage lambda with the
      chimeric terminase is unable to form plaques, but pseudorevertants are readily
      obtained. Some pseudorevertants have trans-acting suppressors that change codons
      of the recognition helix. Some of these codons appear to remove an unfavorable
      base-pair contact; others appear to create a novel nonspecific DNA contact.
      Helper-packaging experiments show that these mutant terminases have lost the
      ability to discriminate between lambda and 21 during DNA packaging. Two cis
      acting suppressors affect cosB, the small subunit's DNA-binding site. Each
      changes a cosB(lambda)-specific base pair to a cosB(21)-specific base pair. These
      cosB suppressors cause enhanced DNA packaging by 21-specific terminase and reduce
      packaging by lambda-terminase. Both the cognate support helix and turn are
      required for strong packaging discrimination. The wing does not contribute to
      cosB specificity. Evolution of packaging specificity is discussed, including a
      model in which lambda- and 21-packaging specificities diverged from a common
      ancestor phage with broad packaging specificity.

PMID- 19841095
TI  - Genetic testing of the hypothesis that hybrid male lethality results from a
      failure in dosage compensation.
AB  - Several recent studies have suggested that F(1) hybrid male lethality in crosses
      between Drosophila melanogaster and D. simulans is due to a failure in dosage
      compensation, caused by incompatibilities between D. simulans dosage compensation
      proteins and the D. melanogaster X chromosome. Contrary to the predictions of
      this hypothesis, mutations in four essential D. melanogaster dosage compensation
      genes are shown here to moderately increase rather than decrease hybrid male
      viability.

PMID- 19841100
TI  - Is T1G3 bladder cancer having a definite muscle layer in TUR specimens a highly
      progressive disease?
AB  - OBJECTIVE: Patients with T1G3 bladder cancer are at high risk of progression to
      muscle-invasive cancer, and early cystectomy is considered as a treatment option
      in this particular situation. On the other hand, understaging of T1G3 bladder
      cancer has been gradually proven as second or repeat transurethral resection
      (TUR) has been widely applied. To evaluate the real rate of progression, we
      investigated the prognosis of T1G3 bladder cancer in which a muscle layer was
      histologically confirmed in the TUR specimens. METHODS: We retrospectively
      reviewed 48 patients with primary T1G3 bladder cancer in which a muscle layer in
      the TUR specimens was confirmed between 1990 and 2006 in our institute. We
      investigated recurrence and progression in 45 patients, excluding 3 who were
      immediately treated with radical cystectomy. Fifteen and 12 patients received
      intravesical treatment with bacillus Calmette-Guerin (BCG) and anticancer agents
      just after TUR, respectively. The remaining 18 did not have any such treatment.
      RESULTS: Recurrence and progression were observed in 21 (47%) and 3 patients
      (6.7%), respectively, during a median follow-up period of 42.1 months. The 3-year
      recurrence-free and progression-free survival rates were 54% and 91%,
      respectively. No significant differences were observed in the rates between the
      patients with and without BCG treatment in the study. CONCLUSIONS: There is a
      possibility that the progression rate in patients with T1G3 bladder cancer is not
      as high as previously reported when only patients whose muscle layer was
      histologically confirmed were analyzed. An adequate technique for TUR that
      unmistakably collects the muscle layer may be important to predict the outcome
      accurately.

PMID- 19841101
TI  - Radical prostatectomy for high-risk prostate cancer.
AB  - The prostate-specific antigen (PSA) era has changed the pattern of prostate
      cancer at presentation. Patients now present with lower-stage, lower-risk
      disease. However, some patients continue to present with high-risk prostate
      cancer (high-risk PC), and the effect of PSA introduction on outcome is less
      clear. This review highlights the salient features of why radical prostatectomy
      should be considered in the management of men with high-risk PC (Gleason score 8
      10, marked increase in PSA levels and advanced clinical T stage). Radical
      retropubic prostatectomy (RRP) can provide durable local control, long-term
      cancer-specific survival and accurate pathologic staging, and may guide further
      individualized treatment. For these reasons, RRP remains the best single
      treatment of high-risk PC in operable patients.

PMID- 19841096
TI  - Participation of DNA polymerase zeta in replication of undamaged DNA in
      Saccharomyces cerevisiae.
AB  - Translesion synthesis DNA polymerases contribute to DNA damage tolerance by
      mediating replication of damaged templates. Due to the low fidelity of these
      enzymes, lesion bypass is often mutagenic. We have previously shown that, in
      Saccharomyces cerevisiae, the contribution of the error-prone DNA polymerase zeta
      (Polzeta) to replication and mutagenesis is greatly enhanced if the normal
      replisome is defective due to mutations in replication genes. Here we present
      evidence that this defective-replisome-induced mutagenesis (DRIM) results from
      the participation of Polzeta in the copying of undamaged DNA rather than from
      mutagenic lesion bypass. First, DRIM is not elevated in strains that have a high
      level of endogenous DNA lesions due to defects in nucleotide excision repair or
      base excision repair pathways. Second, DRIM remains unchanged when the level of
      endogenous oxidative DNA damage is decreased by using anaerobic growth
      conditions. Third, analysis of the spectrum of mutations occurring during DRIM
      reveals the characteristic error signature seen during replication of undamaged
      DNA by Polzeta in vitro. These results extend earlier findings in Escherichia
      coli indicating that Y-family DNA polymerases can contribute to the copying of
      undamaged DNA. We also show that exposure of wild-type yeast cells to the
      replication inhibitor hydroxyurea causes a Polzeta-dependent increase in
      mutagenesis. This suggests that DRIM represents a response to replication
      impediment per se rather than to specific defects in the replisome components.

PMID- 19841102
TI  - A two-step intensity-modulated radiation therapy method for nasopharyngeal
      cancer: the Kinki University experience.
AB  - OBJECTIVE: The aim of this study was to analyze the clinical results of our
      adaptive radiation therapy scheme of a two-step intensity-modulated radiotherapy
      (IMRT) method for nasopharyngeal cancer (NPC) at Kinki University Hospital.
      METHODS: Between 2000 and 2007, 35 patients with Stage I-IVB NPC treated by IMRT
      were included. For all patients, treatment-planning computed tomography was done
      twice before and during IMRT to a total dose of 60-70 Gy/28-35 fractions (median
      68 Gy). Chemotherapy (cisplatin 80 mg/m(2)/3 weeks x 1-3 courses) was given
      concurrently with IMRT for 31 patients. RESULTS: The 3- and 5-year overall
      survival rates for the 31 patients treated with concurrent chemotherapy were 88%
      and 83%, respectively. The 3- and 5-year loco-regional control rates for the 31
      patients were 93% and 87%, respectively. Planning target volume delineation for
      the primary site or involved nodes was insufficient for three early cases,
      resulting in marginal recurrence in the three patients (9%). Except for one
      patient with early death, xerostomia scores at 1-2 years were: Grade 0, 11; Grade
      1, 17; Grade 2, 5; Grade 3, 1. CONCLUSIONS: Excellent overall survival and loco
      regional control rates were obtained by a two-step IMRT method with concurrent
      chemotherapy for NPC, although marginal recurrence was noted in some early cases.

PMID- 19841103
TI  - Suicide associated with corticosteroid use during chemotherapy: case report.
AB  - Corticosteroids are widely known to have a variety of adverse mental effects.
      Although corticosteroids are frequently used to prevent vomiting induced by
      chemotherapeutic agent, their mental effects have received little attention in
      oncology settings. We report the case of a patient who experienced severe
      depressive symptoms after both the first and second course of treatment with a
      corticosteroid during chemotherapy and ultimately committed suicide. The temporal
      and dose-response relationships suggested a possible association between the
      depressive symptoms and corticosteroid. We ultimately speculated that
      corticosteroid withdrawal induced the depressive symptoms in this case. This case
      should alert clinical oncologists to pay attention to mental symptoms after
      prescribing a corticosteroid.

PMID- 19841104
TI  - Oestradiol assays: fitness for purpose?
AB  - In this review we discuss the analytical inadequacies of oestradiol assays in
      relation to the clinical requirements for performing them, and make
      recommendations for their improvement. The measurement of oestradiol can be
      requested in a number of clinical scenarios (precocious puberty, infertility,
      assisted conception, hormone replacement therapy). The very wide dynamic range of
      oestradiol concentrations is a huge challenge for routine assays, which they are
      unlikely to meet on theoretical as well as practical grounds. The EQA performance
      of oestradiol assays in terms of trueness, comparability, recovery and analytical
      sensitivity leaves much to be desired and indicates that calibration is
      compromised by poor analytical specificity. To make oestradiol assays fit for
      purpose requires concerted action by all stakeholders to define analytical
      quality specifications for the various clinical scenarios involved, and then to
      encourage concerted action by the diagnostic industry to use the steroid
      reference measurement system to improve specificity, trueness and traceability.

PMID- 19841105
TI  - Circulating ghrelin exists in both lipoprotein bound and free forms.
AB  - INTRODUCTION: Ghrelin is a gastric peptide that has been implicated in the
      development of obesity and cardiovascular disease. It has been reported that
      ghrelin binds to lipoproteins, although the different binding patterns of
      acylated ghrelin (AG) and unacylated ghrelin (UAG) are still to be determined.
      METHODS: Lipoprotein fractions were generated using a self-generating iodixanol
      gradient. AG and UAG were measured using specific enzyme immunoassays. RESULTS:
      AG bound to all lipoproteins in approximately equal concentrations (VLDL 26%, LDL
      22%, HDL 23%) and was present as a plasma protein (27%). UAG bound more
      specifically to HDL (49%) and was present as a plasma protein (48%). CONCLUSIONS:
      The different binding patterns of AG and UAG may have significant implications
      for their biological effects, including roles in energy metabolism, the
      development of obesity and potentially in the modulation of cardiovascular
      disease.

PMID- 19841106
TI  - Exploring the relationship among weight, race, and sexual behaviors among girls.
AB  - OBJECTIVE: The relationship between weight and sexual behavior among adolescents
      is poorly understood. We examined this relationship in a nationally
      representative sample of high school girls. METHODS: We performed a cross
      sectional analysis of self-reported data from 7193 high school girls who
      completed the 2005 Youth Risk Behavior Surveillance survey. We used multivariate
      logistic regression to examine associations among 3 weight indices (BMI
      calculated from self-reported weight and height, perceived weight, and weight
      misperception) and 6 sexual behaviors (ever had vaginal sex; sex before age 13;
      >or=4 sexual partners; and alcohol, condom, and oral contraceptive use at last
      sex) adjusting for age, race/ethnicity, and a history of intimate partner
      violence. RESULTS: There were no differences in the likelihood of ever having sex
      on the basis of BMI or weight perception accuracy; however, girls who perceived
      themselves as overweight were less likely to have ever had sex. Among sexually
      active girls, those who had low BMI and perceived themselves as overweight or had
      overweight misperceptions were less likely to report condom use at last sex.
      Sexually active girls who perceived themselves as overweight were also more
      likely to have had sex before age 13. Associations between the 3 weight indices
      and sexual risk behaviors varied across racial/ethnic groups. CONCLUSIONS: Sexual
      risk behaviors may be more common among girls who are underweight or perceive
      themselves (accurately or not) to be overweight and vary by racial/ethnic group.
      This suggests that girls at weight extremes and those from different racial
      backgrounds may have unique sexual health education and prevention needs.

PMID- 19841107
TI  - Short nighttime sleep-duration and hyperactivity trajectories in early childhood.
AB  - OBJECTIVES: Our objectives were to investigate the developmental trajectories of
      nighttime sleep duration and hyperactivity over the preschool years and to
      identify the risk factors associated with short nighttime sleep duration and high
      hyperactivity scores. DESIGN, SETTING, AND PARTICIPANTS: Nighttime sleep duration
      and hyperactivity were measured yearly by questionnaires administered to mothers
      of 2057 children from age 1.5 to 5 years. Developmental trajectories of nighttime
      sleep duration and hyperactivity throughout early childhood were analyzed to
      determine interassociations. A multinomial logistic regression was performed to
      determine which factors among selected child, maternal, and family
      characteristics and parental practices surrounding sleep periods in early
      childhood were associated with short nighttime sleep duration and high
      hyperactivity scores. RESULTS: The trajectories of nighttime sleep duration and
      hyperactivity were significantly associated. The odds ratio (OR) of reporting
      short nighttime sleep duration was 5.1 for highly hyperactive children
      (confidence interval [CI]: 3.2-7.9), whereas the OR of reporting high
      hyperactivity scores was 4.2 for persistently short sleepers (CI: 2.7-6.6). The
      risk factors for reporting short nighttime sleep duration and high hyperactivity
      scores were (1) being a boy, (2) having insufficient household income, (3) having
      a mother with a low education, and (4) being comforted outside the bed after a
      nocturnal awakening at 1.5 years of age. CONCLUSIONS: The risk of short nighttime
      sleep duration in highly hyperactive children is greater than the risk of high
      hyperactivity scores in short sleepers. Preventive interventions that target boys
      living in adverse familial conditions could be used to address these concomitant
      behavioral problems.

PMID- 19841108
TI  - From the American Academy of Pediatrics: Policy statement--Tobacco use: a
      pediatric disease.
AB  - Tobacco use and secondhand tobacco-smoke (SHS) exposure are major national and
      international health concerns. Pediatricians and other clinicians who care for
      children are uniquely positioned to assist patients and families with tobacco-use
      prevention and treatment. Understanding the nature and extent of tobacco use and
      SHS exposure is an essential first step toward the goal of eliminating tobacco
      use and its consequences in the pediatric population. The next steps include
      counseling patients and family members to avoid SHS exposures or cease tobacco
      use; advocacy for policies that protect children from SHS exposure; and
      elimination of tobacco use in the media, public places, and homes. Three
      overarching principles of this policy can be identified: (1) there is no safe way
      to use tobacco; (2) there is no safe level or duration of exposure to SHS; and
      (3) the financial and political power of individuals, organizations, and
      government should be used to support tobacco control. Pediatricians are advised
      not to smoke or use tobacco; to make their homes, cars, and workplaces tobacco
      free; to consider tobacco control when making personal and professional
      decisions; to support and advocate for comprehensive tobacco control; and to
      advise parents and patients not to start using tobacco or to quit if they are
      already using tobacco. Prohibiting both tobacco advertising and the use of
      tobacco products in the media is recommended. Recommendations for eliminating SHS
      exposure and reducing tobacco use include attaining universal (1) smoke-free
      home, car, school, work, and play environments, both inside and outside, (2)
      treatment of tobacco use and dependence through employer, insurance, state, and
      federal supports, (3) implementation and enforcement of evidence-based tobacco
      control measures in local, state, national, and international jurisdictions, and
      (4) financial and systems support for training in and research of effective ways
      to prevent and treat tobacco use and SHS exposure. Pediatricians, their staff and
      colleagues, and the American Academy of Pediatrics have key responsibilities in
      tobacco control to promote the health of children, adolescents, and young adults.

PMID- 19841110
TI  - From the American Academy of Pediatrics: Technical report--Secondhand and
      prenatal tobacco smoke exposure.
AB  - Secondhand tobacco smoke (SHS) exposure of children and their families causes
      significant morbidity and mortality. In their personal and professional roles,
      pediatricians have many opportunities to advocate for elimination of SHS exposure
      of children, to counsel tobacco users to quit, and to counsel children never to
      start. This report discusses the harms of tobacco use and SHS exposure, the
      extent and costs of tobacco use and SHS exposure, and the evidence that supports
      counseling and other clinical interventions in the cycle of tobacco use.
      Recommendations for future research, policy, and clinical practice change are
      discussed. To improve understanding and provide support for these activities, the
      harms of SHS exposure are discussed, effective ways to eliminate or reduce SHS
      exposure are presented, and policies that support a smoke-free environment are
      outlined.

PMID- 19841111
TI  - Prospective, observational study of outcomes in neonates with severe
      thrombocytopenia.
AB  - OBJECTIVE: A cross-sectional, observational study of outcomes for neonates with
      severe neonatal thrombocytopenia (SNT; platelet count of <60 x 10(9) platelets
      per L) was performed to examine hemorrhage and use of platelet transfusions.
      METHODS: Neonates who were admitted to 7 NICUs and developed SNT were enrolled
      for daily data collection. RESULTS: Among 3652 neonatal admissions, 194 neonates
      (5%) developed SNT. The median gestational age of 169 enrolled neonates was 27
      weeks (interquartile range [IQR]: 24-32 weeks), and the median birth weight was
      822 g (IQR: 670-1300 g). Platelet count nadirs were <20 x 10(9), 20 to 39 x
      10(9), and 40 to 59 x 10(9) platelets per L for 58 (34%), 64 (39%), and 47 (28%)
      of all enrolled infants, respectively. During the study, 31 infants (18%) had no
      recorded hemorrhage, 123 (73%) developed minor hemorrhage, and 15 (9%) developed
      major hemorrhage. Thirteen (87%) of 15 episodes of major hemorrhage occurred in
      neonates with gestational ages of <28 weeks. Platelet transfusions (n = 415) were
      administered to 116 infants (69%); for 338 (81%) transfusions, the main recorded
      reason was low platelet count. Transfusions increased the platelet count from a
      median of 27 x 10(9) platelets per L (IQR: 19-36 x 10(9) platelets per L) to 79 x
      10(9) platelets per L (IQR: 47.5-127 x 10(9) platelets per L). CONCLUSIONS:
      Although one third of neonates enrolled in this study developed thrombocytopenia
      of <20 x 10(9) platelets per L, 91% did not develop major hemorrhage. Most
      platelet transfusions were given to neonates with thrombocytopenia with no
      bleeding or minor bleeding only.

PMID- 19841109
TI  - Parent- versus child-reported functional health status after the Fontan
      procedure.
AB  - OBJECTIVE: We sought to compare perceptions of functional health status between
      children who had undergone a Fontan procedure and their parents. METHODS: Fontan
      procedure survivors 10 to 18 years of age were included in the study if the child
      completed the Child Health Questionnaire (CHQ) and the parent completed the
      parent form to assess the child's functional health status. Comparisons were made
      between raw domain scores for the parent- and child-completed CHQs. RESULTS:
      Between March 2003 and April 2004, 1078 Fontan survivors were screened. Of the
      546 eligible and consented patients, 354 were 10-18 years of age and 328
      parent/child pairs completed the CHQs. Parents reported significantly lower
      scores (worse functioning) for their children than the children reported for
      themselves in the domains of physical functioning (P < .01), impact on school or
      activities from emotional and behavioral problems (P < .01), impact on school or
      activities from physical health issues (P < .01), general behavior (P < .01),
      mental health (P < .01), self-esteem (P < .01), and general health perceptions (P
      < .01). No significant differences were noted for the domains of bodily pain,
      family cohesiveness, or family activities. For the physical functioning domain,
      factors contributing to lower scores for parent versus child reports included
      pulmonary artery anomalies and fenestration at the time of the Fontan operation.
      Lower parent-reported scores also were associated with more noncardiac health
      problems in the child. CONCLUSIONS: Parents' perceptions of the functional health
      status of their children after the Fontan procedure were worse than the
      children's perceptions.

PMID- 19841112
TI  - Can association between preterm birth and autism be explained by maternal or
      neonatal morbidity?
AB  - OBJECTIVE: We examined whether an association between preterm birth and risk of
      autistic disorders could be explained by pregnancy complications or neonatal
      morbidity. METHODS: This Swedish, population-based, case-control study included
      1216 case subjects with autistic disorders who were born between 1987 and 2002
      and 6080 control subjects who were matched with respect to gender, birth year,
      and birth hospital. We assessed associations between gestational age and autistic
      disorders and adjusted for maternal, birth, and neonatal characteristics.
      Conditional logistic regression was used to estimate odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: Compared with infants born at term, the
      unadjusted ORs for autistic disorders among very and moderately preterm infants
      were 2.05 [95% CI: 1.26-3.34] and 1.55 [95% CI: 1.22-1.96], respectively. When we
      controlled for maternal, pregnancy, and birth characteristics, ORs were reduced
      to 1.48 [95% CI: 0.77-2.84] and 1.33 [95% CI: 0.98-1.81], respectively. When we
      also controlled for neonatal complications, ORs were 0.98 [95% CI: 0.45-2.16] and
      1.25 [95% CI: 0.90-1.75], respectively. Reductions in risks of autistic disorders
      related to preterm birth were primarily attributable to preeclampsia, small-for
      gestational age birth, congenital malformations, low Apgar scores at 5 minutes,
      and intracranial bleeding, cerebral edema, or seizures in the neonatal period.
      Neonatal hypoglycemia, respiratory distress, and neonatal jaundice were
      associated with increased risk of autistic disorders for term but not preterm
      infants. CONCLUSION: The increased risk of autistic disorders related to preterm
      birth is mediated primarily by prenatal and neonatal complications that occur
      more commonly among preterm infants.

PMID- 19841114
TI  - Multistate outbreak of Salmonella infections associated with small turtle
      exposure, 2007-2008.
AB  - OBJECTIVE: Turtle-associated salmonellosis was increasingly recognized in the
      United States during the 1960s, leading to a federal ban in 1975 on the sale of
      turtles <4 inches in carapace length (small turtles). Although sporadic reports
      of turtle-associated Salmonella are frequent, outbreaks are rare. In September
      2007, several patients with Salmonella enterica serotype Paratyphi B var Java
      infections reported recent turtle exposure. We conducted an investigation to
      determine the source and extent of the infections. PATIENTS AND METHODS: Patients
      with Salmonella Paratyphi B var Java infections with a specific pulsed-field gel
      electrophoresis pattern (outbreak strain) and illness onset between May 2007 and
      January 2008, were compared with healthy controls. Reptile exposure and awareness
      of a Salmonella-reptile link were assessed. Turtle size and purchase information
      were collected. RESULTS: We identified 107 patients with outbreak-strain
      infections. The median patient age was 7 years; 33% were hospitalized. Forty
      seven (60%) of 78 patients interviewed reported exposure to turtles during the
      week before illness; 41 (87%) were small turtles, and 16 (34%) were purchased in
      a retail pet store. In the case-control study, 72% of 25 patients reported turtle
      exposure during the week before illness compared with 4% of 45 controls (matched
      odds ratio [mOR]: 40.9 [95% confidence interval (CI): 6.9-unbounded]). Seven
      (32%) of 22 patients versus 11 (28%) of 39 controls reported knowledge of a link
      between reptile exposure and Salmonella infection (mOR: 1.3 [95% CI: 0.4-4.6]).
      CONCLUSIONS: We observed a strong association between turtle exposure and
      Salmonella infections in this outbreak. Small turtles continue to be sold and
      pose a health risk, especially to children; many people remain unaware of the
      link between Salmonella infection and reptile contact.

PMID- 19841115
TI  - The Health and Obesity: Prevention and Education (HOPE) Curriculum Project-
      curriculum development.
AB  - The Health and Obesity: Prevention and Education (HOPE) project is a
      multidisciplinary, healthy living counseling curriculum to educate pediatric
      clinicians in training on how to recognize children who are at risk for obesity
      and its comorbidities and how to promote healthy weight among children and their
      families. Curriculum topics were selected by experts of nutrition, medicine,
      dentistry, behavioral counseling, and education and incorporate the recent 2007
      Expert Committee recommendations regarding the prevention, assessment, and
      treatment of childhood and adolescent obesity. The HOPE curriculum instructs
      medical and dental clinicians on the health consequences of childhood obesity and
      screening techniques to identify children and families at risk, reviews the
      current evidence for health intervention recommendations, and teaches trainees
      regarding the theoretical rationale and art of constructive and culturally
      sensitive weight counseling for behavioral change. Although designed and tailored
      specifically for and currently available medical and dental trainees, the HOPE
      curriculum is Web-based and will also be made available to currently practicing
      clinicians across the United States beginning in winter 2009. This educational
      tool, grounded in understanding of relevant sciences, literature, and research
      methods, provides clinicians with the skills necessary to identify and counsel
      patients who are at risk to promote healthy weight among youth. This article
      discusses the approach and methods used for curriculum development. Future
      publications will discuss HOPE project implementation and outcomes.

PMID- 19841113
TI  - Who will care for me next? Transitioning to adulthood with hydrocephalus.
AB  - OBJECTIVES: Hydrocephalus is a prototypical chronic condition that follows
      children into adulthood. The objectives of this study were to (1) review how the
      health care needs of young adults with hydrocephalus are not being met, (2)
      estimate the numbers of adults with childhood-onset hydrocephalus, (3) describe a
      novel program to provide care for young adults with hydrocephalus and other
      chronic pediatric conditions, and (4) propose national strategies to promote
      successful hydrocephalus transition care. RESULTS: Adults with hydrocephalus need
      continuous access to expert surgical and medical providers. Existing care models
      fail to meet this need. The number of young adults who have hydrocephalus, are
      aged 18 to 35 and need treatment in the United States is predicted to exceed
      40000 annually within the next 2 decades. We are developing integrated teams of
      pediatric and adult medical and surgical specialists to provide continuous,
      coordinated, comprehensive care for individuals with hydrocephalus in a pediatric
      setting. This setting will train our future physician workforce on optimal
      transition care. Coordinated national efforts are also needed. CONCLUSIONS:
      Providers need to implement appropriate management and transition care for
      individuals with hydrocephalus. We must work at local and national levels to
      transform the care model, improve the quality of health care delivery, and
      improve outcomes for young adults with hydrocephalus.

PMID- 19841116
TI  - Secondhand tobacco smoke exposure among children and adolescents: United States,
      2003-2006.
AB  - OBJECTIVE: The implementation of policies that prohibit tobacco smoking in public
      places has resulted in a significant reduction in secondhand smoke (SHS) exposure
      in the US population; however, such policies do not extend to private homes,
      where children continue to be exposed. Our objective was to assess SHS exposure
      among US children and adolescents by using serum cotinine measures to compare
      those who were exposed to SHS in the home and those without home exposure.
      METHODS: We analyzed serum cotinine data from the 2003-2006 National Health and
      Nutrition Examination Survey for 5518 children (3-11 years) and nonsmoking
      adolescents (12-19 years). We calculated geometric mean serum cotinine levels by
      sociodemographic and household characteristics according to self-reported home
      SHS exposure. Multiple regression analysis was conducted to evaluate independent
      predictors of serum cotinine levels. RESULTS: Geometric mean serum cotinine
      levels were 1.05 ng/mL among those with home SHS exposure and 0.05 ng/mL among
      those without home exposure. Among children who were exposed to SHS at home,
      serum cotinine levels were inversely associated with age and were similar for non
      Hispanic black and non-Hispanic white children. Conversely, among children
      without SHS exposure at home, serum cotinine levels were higher among non
      Hispanic black compared with non-Hispanic white children, and there was no
      relationship with age. Mexican American children had the lowest level of SHS
      exposure. CONCLUSIONS: Serum cotinine levels were an order of magnitude higher
      among children with reported SHS exposure at home compared with those with no
      exposure in the home.

PMID- 19841117
TI  - A medical home versus temporary housing: the importance of a stable usual source
      of care.
AB  - OBJECTIVES: Little is known about how the stability of a usual source of care
      (USC) affects access to care. We examined the prevalence of USC changes among low
      income children and how these changes were associated with unmet health care
      need. METHODS: We conducted a cross-sectional survey of Oregon's food stamp
      program in 2005. We analyzed primary data from 2681 surveys and then weighted
      results to 84087 families, adjusting for oversampling and nonresponse. We then
      ascertained the percentage of children in the Oregon population who had ever
      changed a USC for insurance reasons, which characteristics were associated with
      USC change, and how USC change was associated with unmet need. We also conducted
      a posthoc analysis of data from the Medical Expenditure Panel Survey to confirm
      similarities between the Oregon sample and a comparable national sample. RESULTS:
      Children without a USC in the Oregon population had greater odds of reporting an
      unmet health care need than those with a USC. This pattern was similar in
      national estimates. Among the Oregon sample, 23% had changed their USC because of
      insurance reasons, and 10% had no current USC. Compared with children with a
      stable USC, children who had changed their USC had greater odds of reporting
      unmet medical need, unmet prescription need, delayed care, unmet dental need, and
      unmet counseling need. CONCLUSIONS: This study highlights the importance of
      ensuring stability with a USC. Moving low-income children into new medical homes
      could disturb existing USC relationships, thereby merely creating "temporary
      housing."

PMID- 19841118
TI  - From the American Academy of Pediatrics: Policy statement--Media violence.
AB  - Exposure to violence in media, including television, movies, music, and video
      games, represents a significant risk to the health of children and adolescents.
      Extensive research evidence indicates that media violence can contribute to
      aggressive behavior, desensitization to violence, nightmares, and fear of being
      harmed. Pediatricians should assess their patients' level of media exposure and
      intervene on media-related health risks. Pediatricians and other child health
      care providers can advocate for a safer media environment for children by
      encouraging media literacy, more thoughtful and proactive use of media by
      children and their parents, more responsible portrayal of violence by media
      producers, and more useful and effective media ratings. Office counseling has
      been shown to be effective.

PMID- 19841119
TI  - Heel-lancing in newborns: behavioral and spectral analysis assessment of pain
      control methods.
AB  - OBJECTIVE: Pain experience can alter clinical outcome, brain development, and
      subsequent behavior in newborns, primarily in preterm infants. The aims of this
      study were (1) to evaluate several simple, commonly used methods for pain control
      in newborns and (2) to evaluate the concordance between behavioral and autonomic
      cardiac reactivity to pain in term neonates during heel-lancing. METHODS: A
      prospective study was conducted of 180 term newborn infants who were undergoing
      heel-lancing for routine neonatal screening of phenylketonuria and
      hypothyroidism. Newborns were assigned to 6 groups: (1) control (no pain relief
      intervention); (2) nonnutritive sucking; (3) holding by mother; (4) oral glucose
      solution; (5) oral formula feeding; or (6) breastfeeding. Outcome measures
      included the Neonatal Facial Coding System score; cry duration; and autonomic
      variables obtained from spectral analysis of heart rate variability before,
      during, and after heel-lancing. RESULTS: Infants with no pain control showed the
      highest pain manifestation compared with newborns to whom pain control was
      provided. Infants who breastfed or received an oral formula showed the lowest
      increase in heart rate (21 and 23 beats per minute, respectively, vs 36; P <
      .01), lowest neonatal facial score (2.3 and 2.9, respectively, vs 7.1; P < .001),
      lowest cry duration (5 and 13 seconds, respectively, vs 49; P < .001), and lowest
      decrease in parasympathetic tone (-2 and -2.4, respectively, vs 1.2; P < .02)
      compared with the other groups. CONCLUSIONS: Any method of pain control is better
      than none. Feeding and breastfeeding during heel-lancing were found to be the
      most effective methods of pain relief.

PMID- 19841120
TI  - From the American Academy of Pediatrics: Technical report--Tobacco as a substance
      of abuse.
AB  - Tobacco use is the leading preventable cause of morbidity and death in the United
      States. Because 80% to 90% of adult smokers began during adolescence, and two
      thirds became regular, daily smokers before they reached 19 years of age, tobacco
      use may be viewed as a pediatric disease. Every year in the United States,
      approximately 1.4 million children younger than 18 years start smoking, and many
      of them will die prematurely from a smoking-related disease. Moreover, there is
      recent evidence that adolescents report symptoms of tobacco dependence early in
      the smoking process, even before becoming daily smokers. The prevalence of
      tobacco use is higher among teenagers and young adults than among older adult
      populations. The critical role of pediatricians in helping to reduce tobacco use
      and addiction and secondhand tobacco-smoke exposure in the pediatric population
      includes education and prevention, screening and detection, and treatment and
      referral.

PMID- 19841121
TI  - Asthma morbidity among children evaluated by asthma case detection.
AB  - OBJECTIVE: Population-based asthma detection is a potential strategy to reduce
      asthma morbidity in children; however, the burden of respiratory symptoms and
      health care use among children identified by case detection is not well known.
      METHODS: Data come from a school-based asthma case detection validation study of
      3539 children. Respiratory symptoms, emergency department (ED) visits, and
      hospitalizations were assessed by questionnaire for children whose case detection
      result and physician study diagnosis agreed. RESULTS: Physician evaluation of 530
      case detection results yielded 420 cases of agreement (168 children with
      previously diagnosed asthma, 39 with undiagnosed asthma, and 213 without asthma).
      Children with previously diagnosed asthma were more likely to be male (P <
      .0001). No differences in severity were observed in children with previously and
      undiagnosed asthma (P = .31). Children with undiagnosed asthma reported less
      frequent daytime and nighttime symptoms than children with previously diagnosed
      asthma but more than those without asthma (P < .0001). The proportion of children
      with at least 1 respiratory-related ED visit in the past year was 32%, 3%, and 3%
      for those with previously diagnosed, undiagnosed, and no asthma, respectively (P
      < .0001). The proportion with at least 1 respiratory-related hospitalization was
      8%, 0%, and 0%, respectively (P < .0001). There were no differences in
      nonrespiratory ED visits (P = .93). CONCLUSIONS: Despite similar physician-rated
      severity, children with undiagnosed asthma reported significantly less frequent
      respiratory symptoms and health care use than children with previously diagnosed
      asthma. These findings suggest that the potential health gains from case
      detection may be smaller than expected.

PMID- 19841122
TI  - The brains of very preterm newborns in clinically stable condition may be
      hyperoxygenated.
AB  - OBJECTIVE: The objective was to compare cerebral oxygenation in preterm newborns
      with that in healthy term newborns. METHODS: Forty-six preterm newborns with
      gestational ages of <33 weeks and 25 healthy term newborns were included. The
      cerebral tissue oxygenation index (c-TOI) was measured by using near-infrared
      spectroscopy in clinical steady state on the first day of life (median age: 19.2
      hours). The mean gestational ages and birth weights in the 2 groups were 29.1 +/-
      2.6 weeks versus 39.7 +/- 1.3 weeks and 1307 +/- 437 g versus 3484 +/- 346 g,
      respectively. Three preterm infants needed mechanical ventilation and 11 received
      inotropic drugs. Later, 3 preterm infants developed intraventricular hemorrhage
      and 2 infants died. All term infants were healthy newborns recruited in the
      maternity ward. RESULTS: There was a significant difference in c-TOI (preterm:
      78.6% [95% confidence interval: 76.9%-80.3%]; term: 74.7% [95% confidence
      interval: 72.3%-77.1%]). Preterm newborns had significantly lower fractional
      tissue oxygen extraction, which suggests lower oxygen extraction in this group.
      There was no significant correlation between head size and c-TOI. The mean
      peripheral oxygen saturation was 95% in both groups. The median blood Pco(2) for
      the preterm infants was 6.1 kPa (range: 3.4-7.3 kPa). CONCLUSIONS: Cerebral
      oxygenation on the first day of life was higher in a group of relatively healthy,
      very preterm infants in stable condition, compared with healthy term newborns.
      Slightly elevated blood Pco(2) could be the explanation. Prematurity itself does
      not seem to dispose preterm infants to global cerebral hypoxia.

PMID- 19841123
TI  - Acute heart failure syndromes in the pediatric emergency department.
AB  - OBJECTIVE: The objectives of this study were to (1) describe the clinical
      presentation of acute heart failure syndromes (AHFS) in the pediatric emergency
      department (ED) and (2) determine the physician treatment regimens and outcomes
      in the same population. METHODS: This was a cross-sectional study of patients who
      presented with AHFS to the ED at our institution from January 2003 to October
      2006. We defined AHFS as "the gradual or rapid deterioration in heart failure
      signs and symptoms resulting in a need for urgent therapy." Patients were
      included when they had documented signs or symptoms of HF attributable to
      ventricular dysfunction. Patients were excluded when they were older than 21
      years or had HF symptoms that were attributable to left-to-right intracardiac
      shunting or left-sided obstructive lesions. All eligible ED patient visits were
      adjudicated by a pediatric HF specialist. RESULTS: Fifty-seven patient visits to
      the ED met inclusion criteria. There was a significant difference in time from
      arrival to treatment with a diuretic when the therapy was started in the ED
      rather than in the inpatient units. Median time to initiation of a vasoactive
      agent was significantly less for patients whose infusions were started in the ED
      compared with the ICU. Two patients died in the ED, and overall mortality or need
      for mechanical circulatory support for hospitalized patients was 18% (n = 10).
      CONCLUSIONS: These data yield important insight into the clinical features and
      initial treatment of children who present with AHFS in the ED and may allow for
      improved recognition and treatment of this clinical syndrome.

PMID- 19841124
TI  - From the American Academy of Pediatrics: Policy statement--Impact of music, music
      lyrics, and music videos on children and youth.
AB  - Music plays an important role in the socialization of children and adolescents.
      Popular music is present almost everywhere, and it is easily available through
      the radio, various recordings, the Internet, and new technologies, allowing
      adolescents to hear it in diverse settings and situations, alone or shared with
      friends. Parents often are unaware of the lyrics to which their children are
      listening because of the increasing use of downloaded music and headphones.
      Research on popular music has explored its effects on schoolwork, social
      interactions, mood and affect, and particularly behavior. The effect that popular
      music has on children's and adolescents' behavior and emotions is of paramount
      concern. Lyrics have become more explicit in their references to drugs, sex, and
      violence over the years, particularly in certain genres. A teenager's preference
      for certain types of music could be correlated or associated with certain
      behaviors. As with popular music, the perception and the effect of music-video
      messages are important, because research has reported that exposure to violence,
      sexual messages, sexual stereotypes, and use of substances of abuse in music
      videos might produce significant changes in behaviors and attitudes of young
      viewers. Pediatricians and parents should be aware of this information.
      Furthermore, with the evidence portrayed in these studies, it is essential for
      pediatricians and parents to take a stand regarding music lyrics.

PMID- 19841125
TI  - Economic evaluation of inhaled nitric oxide in preterm infants undergoing
      mechanical ventilation.
AB  - OBJECTIVE: In the previously reported Nitric Oxide for Chronic Lung Disease (NO
      CLD) trial, ventilated preterm infants who received a course of inhaled nitric
      oxide (iNO) between 7 and 21 days of life had a significant improvement in
      survival without bronchopulmonary dysplasia (BPD), as well as a shorter duration
      of admission and ventilation. However, the price for the drug may be a barrier to
      widespread use. We sought to estimate the incremental cost-effectiveness of iNO
      therapy to prevent BPD in infants of <1250 g birth weight. METHODS: We used
      patient-level data from the NO CLD randomized trial. The study took a third-party
      payer perspective and measured costs and effects through hospital discharge. We
      applied previously reported hospital per-diem costs stratified according to
      intensity of ventilatory support, nitric oxide costs from standard market prices,
      and professional (physician) fees from the Medicare fee schedule. We compared log
      transformed costs by using multivariable modeling and performed incremental cost
      effectiveness analysis with estimation of uncertainty through nonparametric
      bootstrapping. RESULTS: The mean cost per infant was $193125 in the placebo group
      and $194702 in the iNO group (adjusted P = .17). The point estimate for the
      incremental cost per additional survivor without BPD was $21297. For infants in
      whom iNO was initiated between 7 and 14 days of life, the mean cost per infant
      was $187407 in the placebo group and $181525 in the iNO group (adjusted P = .46).
      In this group of early treated infants, there was a 71% probability that iNO
      actually decreased costs while improving outcomes. CONCLUSIONS: Despite its
      higher price relative to many other neonatal therapies, iNO in this trial was not
      associated with higher costs of care, an effect that is likely due to its impact
      on length of stay and ventilation. Indeed, for infants who receive nitric oxide
      between 7 and 14 days of life, the therapy seemed to lower costs while improving
      outcomes.

PMID- 19841126
TI  - Effectiveness of belt positioning booster seats: an updated assessment.
AB  - OBJECTIVE: The objective of this study was to provide an updated estimate of the
      effectiveness of belt-positioning booster (BPB) seats compared with seat belts
      alone in reducing the risk for injury for children aged 4 to 8 years. METHODS:
      Data were collected from a longitudinal study of children who were involved in
      crashes in 16 states and the District of Columbia from December 1, 1998, to
      November 30, 2007, with data collected via insurance claims records and a
      validated telephone survey. The study sample included children who were aged 4 to
      8 years, seated in the rear rows of the vehicle, and restrained by either a seat
      belt or a BPB seat. Multivariable logistic regression was used to determine the
      odds of injury for those in BPB seats versus those in seat belts. Effects of
      crash direction and booster seat type were also explored. RESULTS: Complete
      interview data were obtained on 7151 children in 6591 crashes representing an
      estimated 120646 children in 116503 crashes in the study population. The adjusted
      relative risk for injury to children in BPB seats compared with those in seat
      belts was 0.55. CONCLUSIONS: This study reconfirms previous reports that BPB
      seats reduce the risk for injury in children aged 4 through 8 years. On the basis
      of these analyses, parents, pediatricians, and health educators should continue
      to recommend as best practice the use of BPB seats once a child outgrows a
      harness-based child restraint until he or she is at least 8 years of age.

PMID- 19841127
TI  - Secondhand smoke and respiratory symptoms among adolescent current smokers.
AB  - OBJECTIVE: No study has ever reported the association between persistent
      respiratory symptoms and exposure to secondhand smoke (SHS) in adolescent
      smokers. The impact of SHS exposure on child health could be largely
      underestimated by not taking into account such effects. We investigated the
      association between exposure to SHS and respiratory symptoms among adolescent
      current smokers. METHODS: A total of 32506 students aged 11 to 20 years from 85
      randomly selected secondary schools in Hong Kong completed a self-administered
      questionnaire that included persistent respiratory symptoms (for 3 consecutive
      months in the past 12 months), number of days of SHS exposure per week at home
      and outside home, smoking status, amount of active smoking, and other basic
      demographic characteristics and socioeconomic status. RESULTS: Adolescent current
      smokers who were exposed to SHS at home 1 to 4 and 5 to 7 days/wk were 50% (95%
      confidence interval [CI]: 3%-121%) and 77% (95% CI: 5%-199%) more likely,
      respectively, to report respiratory symptoms compared with those who were
      unexposed (P = .01 for trend). The corresponding figures for exposure outside
      home were 41% (95% CI: 3%-94%) and 85% (95% CI: 31%-161%; P = .004 for trend).
      Such associations were also observed among never-smokers, but they were weaker
      than those among current smokers (P < .01 for interaction). CONCLUSIONS: This is
      the first evidence that SHS exposure is associated with increased risks for
      persistent respiratory symptoms among adolescent current smokers. Health
      promotion programs should aim at SHS reduction as well as smoking cessation among
      adolescent smokers.

PMID- 19841129
TI  - Global gene expression profiling of hyperkeratotic skin lesions from inner
      Mongolians chronically exposed to arsenic.
AB  - The skin is an organ that is highly sensitive to chronic arsenic (As) exposure.
      Skin lesions such as hyperkeratoses (HKs) are common early manifestations of
      arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers
      (NMSCs), but the driving forces behind their formation and how they may
      ultimately progress to NMSCs are unknown. The goal of this study was to examine
      the global gene expression profiles of As-related HKs in an effort to better
      understand gene expression changes that are potentially associated with early
      stages of As carcinogenesis. HK biopsies were removed from individuals living in
      an arsenicosis-endemic region in Inner Mongolia who had been exposed to high As
      levels in their drinking water for >20 years. Gene expression profiling was
      performed on RNA isolated from 7 individuals in this group and from 4 lesion-free
      skin samples from healthy individuals. Consistent with the pathological
      characteristics of the HK lesions, major functional categories and known
      canonical pathways represented by altered transcripts include those involved in
      development, differentiation, apoptosis, proliferation, and stress response. The
      results of this study may help define a signature profile of gene expression
      changes associated with long-term As exposure in the skin.

PMID- 19841128
TI  - Clinical and economic effects of iNO in premature newborns with respiratory
      failure at 1 year.
AB  - BACKGROUND: The long-term consequences of inhaled nitric oxide (iNO) use in
      premature newborns with respiratory failure are unknown. We therefore studied the
      clinical and economic outcomes to 1 year of corrected age after a randomized
      controlled trial of prophylactic iNO. METHODS: Premature newborns (gestational
      age <or=34 w, birth weight 500-1250 g) with respiratory failure randomly received
      5 ppm iNO or placebo within 48 h of birth until 21 d or extubation. We assessed
      clinical outcomes via in-person neurodevelopmental evaluation at 1 y corrected
      age and telephone interviews every 3 m. We estimated costs from detailed hospital
      bills and interviews, converting all costs to 2008 US$. Of 793 trial subjects,
      631 (79.6%) contributed economic data, and 455 (77.1% of survivors) underwent
      neurodevelopmental evaluation. RESULTS: At 1 y corrected age, survival was not
      different by treatment arm (79.2% iNO vs. 74.5% placebo, P = .12), nor were other
      post-discharge outcomes. For subjects weighing 750-999 g, those receiving iNO had
      greater survival free from neurodevelopmental impairment (67.9% vs. 55.6%, P =
      .04). However, in subjects weighing 500-749 g, iNO led to greater oxygen
      dependency (11.7% vs. 4.0%, P = .04). Median total costs were similar ($235,800
      iNO vs. $198,300 placebo, P = .19). Quality-adjusted survival was marginally
      better with iNO (by 0.011 quality-adjusted life-years/subject). The incremental
      cost-effectiveness ratio was $2.25 million/quality-adjusted life-year.
      CONCLUSIONS: Subjects in both arms commonly experienced neurodevelopmental and
      pulmonary morbidity, consuming substantial health care resources. Prophylactic
      iNO beginning in the first days of life did not lower costs and had a poor cost
      effectiveness profile.

PMID- 19841130
TI  - Dietary fat-influenced development of colon neoplasia in Apc Min mice exposed to
      benzo(a)pyrene.
AB  - Colorectal cancer, responsible for 50,000 deaths per year, is a contributing
      factor for considerable mortalities in the United States. Consumption of well
      done red meat and saturated fats rich in polycyclic aromatic hydrocarbons may be
      one of the causative factors for sporadic colon cancer. The objective of this
      study was to investigate whether the formation of colon tumors in adult Apc(Min)
      mice was influenced by the ingestion of different types of fat containing
      benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon compound. Treatment
      consisted of 50 and 100 microg B(a)P/kg body weight dissolved in peanut or
      coconut oil (representatives of unsaturated and saturated fats, respectively)
      administered daily to six-week-old male Apc(Min) mice via oral gavage for sixty
      days. At the end of exposure, mice were sacrificed; jejunum and colons were
      retrieved and preserved in 10% formalin for observation for gross pathological
      changes. An increased prevalence of adenomas in colons of mice that ingested
      B(a)P through saturated dietary fat compared to unsaturated fat and controls (p <
      .05) was noticed. Interestingly, we also observed adenomas with high-grade
      dysplasia in the B(a)P + saturated fat group, and these incidences were frequent
      at the 100 microg/kg B(a)P dose. On the other hand, the B(a)P-alone and
      unsaturated-fat groups did not show significant differences in the numbers of
      adenomas and invasive tumors in the both jejunum and the colon. Our studies
      established that dietary fat, especially saturated fat, potentiates the
      development of colon tumors caused by B(a)P in the Apc(Min) mouse.

PMID- 19841132
TI  - Senthil Muthuswamy: a new road map for cancer. Interview by Caitlin Sedwick.

PMID- 19841133
TI  - JCB meeting: Cell Biology of Disease.

PMID- 19841131
TI  - Differential effects of 17beta-estradiol and of synthetic progestins on
      aldosterone-salt-induced kidney disease.
AB  - Elevated mineralocorticoid levels and female sex hormones have been shown to
      confer opposing effects on renal injury, but their combined effects are still
      unknown. OBJECTIVE: Identify the function of estrogens and of different synthetic
      progestins on aldosterone salt-mediated renal disease. METHODS: The role of
      17beta-estradiol, medroxyprogesterone acetate (MPA), and drospirenone during
      renal injury was studied in Wistar rats subjected to uni-nephrectomy plus
      aldosterone salt treatment. RESULTS: Aldo-salt treatment of intact,
      ovariectomized, and estradiol-treated female rats resulted in remnant kidney
      hypertrophy without structural damage. Co-treatment with MPA, but not with
      drospirenone, increased kidney hypertrophy, fluid turnover, sodium retention, and
      potassium excretion. Medroxyprogesterone acetate also caused glomerular,
      vascular, tubular, and interstitial lesions that were accompanied by increased
      blood pressure and enhanced NADPH oxidase (p67phox) and sodium channel (alpha
      ENaC) expression. Drospirenone, a progestin with anti-mineralocorticoid function,
      and spironolactone prevented kidney hypertrophy, hypertension, and sodium
      retention. Drospirenone and spironolactone also increased renal angiotensin II
      type 2 receptor expression and relieved aldosterone-induced suppression of serum
      angiotensin II levels. CONCLUSION: The choice of specific synthetic progestins
      has profound implications on the development of kidney injury and renal gene
      expression under conditions of elevated aldosterone serum levels and salt intake.

PMID- 19841134
TI  - Keratins and protein synthesis: the plot thickens.
AB  - In addition to protecting epithelial cells from mechanical stress, keratins
      regulate cytoarchitecture, cell growth, proliferation, apoptosis, and organelle
      transport. In this issue, Vijayaraj et al. (2009. J. Cell Biol.
      doi:10.1083/jcb.200906094) expand our understanding of how keratin proteins
      participate in the regulation of protein synthesis through their analysis of mice
      lacking the entire type II keratin gene cluster.

PMID- 19841135
TI  - It takes two to tango to the melanosome.
AB  - The role of clathrin adaptor proteins in sorting cargo in the biosynthetic and
      recycling routes is an area of intense research. In this issue, Delevoye et al.
      (2009. J. Cell Biol. doi:10.1083/jcb.200907122) show that a close interaction
      between the clathrin adaptor AP-1 and a kinesin motor KIF13A is essential for
      delivering melanogenic enzymes from recycling endosomes to nascent melanosomes
      and for organelle biogenesis.

PMID- 19841136
TI  - Keratins regulate protein biosynthesis through localization of GLUT1 and -3
      upstream of AMP kinase and Raptor.
AB  - Keratin intermediate filament proteins form cytoskeletal scaffolds in epithelia,
      the disruption of which affects cytoarchitecture, cell growth, survival, and
      organelle transport. However, owing to redundancy, the global function of
      keratins has not been defined in full. Using a targeted gene deletion strategy,
      we generated transgenic mice lacking the entire keratin multiprotein family. In
      this study, we report that without keratins, embryonic epithelia suffer no
      cytolysis and maintain apical polarity but display mislocalized desmosomes. All
      keratin-null embryos die from severe growth retardation at embryonic day 9.5. We
      find that GLUT1 and -3 are mislocalized from the apical plasma membrane in
      embryonic epithelia, which subsequently activates the energy sensor adenosine
      monophosphate kinase (AMPK). Analysis of the mammalian target of rapamycin (mTOR)
      pathway reveals that AMPK induction activates Raptor, repressing protein
      biosynthesis through mTORC1's downstream targets S6 kinase and 4E-binding protein
      1. Our findings demonstrate a novel keratin function upstream of mTOR signaling
      via GLUT localization and have implications for pathomechanisms and therapy
      approaches for keratin disorders and the analysis of other gene families.

PMID- 19841137
TI  - Cohesin SMC1beta protects telomeres in meiocytes.
AB  - Meiosis-specific mammalian cohesin SMC1beta is required for complete sister
      chromatid cohesion and proper axes/loop structure of axial elements (AEs) and
      synaptonemal complexes (SCs). During prophase I, telomeres attach to the nuclear
      envelope (NE), but in Smc1beta(-/-) meiocytes, one fifth of their telomeres fail
      to attach. This study reveals that SMC1beta serves a specific role at telomeres,
      which is independent of its role in determining AE/SC length and loop extension.
      SMC1beta is necessary to prevent telomere shortening, and SMC3, present in all
      known cohesin complexes, properly localizes to telomeres only if SMC1beta is
      present. Very prominently, telomeres in Smc1beta(-/-) spermatocytes and oocytes
      loose their structural integrity and suffer a range of abnormalities. These
      include disconnection from SCs and formation of large telomeric protein-DNA
      extensions, extended telomere bridges between SCs, ring-like chromosomes,
      intrachromosomal telomeric repeats, and a reduction of SUN1 foci in the NE. We
      suggest that a telomere structure protected from DNA rearrangements depends on
      SMC1beta.

PMID- 19841138
TI  - AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome
      biogenesis.
AB  - Specialized cell types exploit endosomal trafficking to deliver protein cargoes
      to cell type-specific lysosome-related organelles (LROs), but how endosomes are
      specified for this function is not known. In this study, we show that the
      clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral
      recycling endosomal subdomains in melanocytes required for cargo delivery to
      maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of
      recycling endosomes redistributes to pericentriolar clusters, resulting in
      sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and
      consequent inhibition of melanin synthesis and melanosome maturation.
      Immunocytochemistry, live cell imaging, and electron tomography reveal AP-1- and
      KIF13A-dependent dynamic close appositions and continuities between peripheral
      endosomal tubules and melanosomes. Our results reveal that LRO protein sorting is
      coupled to cell type-specific positioning of endosomes that facilitate endosome
      LRO contacts and are required for organelle maturation.

PMID- 19841139
TI  - PIKfyve regulates CaV1.2 degradation and prevents excitotoxic cell death.
AB  - Voltage-gated Ca(2+) channels (VGCCs) play a key role in neuronal signaling but
      can also contribute to cellular dysfunction and death under pathological
      conditions such as stroke and neurodegenerative diseases. We report that
      activation of N-methyl-D-aspartic acid receptors causes internalization and
      degradation of Ca(V)1.2 channels, resulting in decreased Ca(2+) entry and reduced
      toxicity. Ca(V)1.2 internalization and degradation requires binding to
      phosphatidylinositol 3-phosphate 5-kinase (PIKfyve), a lipid kinase which
      generates phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P(2)) and regulates
      endosome and lysosome function. Sustained activation of glutamate receptors
      recruits PIKfyve to Ca(V)1.2 channels, increases cellular levels of
      PtdIns(3,5)P(2), and promotes targeting of Ca(V)1.2 to lysosomes. Knockdown of
      PIKfyve prevents Ca(V)1.2 degradation and increases neuronal susceptibility to
      excitotoxicity. These experiments identify a novel mechanism by which neurons are
      protected from excitotoxicity and provide a possible explanation for neuronal
      death in diseases caused by mutations that affect PtdIns(3,5)P(2) regulation.

PMID- 19841140
TI  - Knee-to-ankle mosaicplasty for the treatment of osteochondral lesions of the
      ankle joint.
AB  - BACKGROUND: Osteochondral lesions are frequently seen in athletes after ankle
      injuries. At this time, osteochondral autologous transplantation (OATS,
      mosaicplasty) is the only surgical treatment that replaces the entire
      osteochondral unit in symptomatic lesions. PURPOSE: To evaluate the clinical and
      radiological midterm to long-term outcome of ankles treated with knee-to-ankle
      mosaicplasty. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Clinical
      evaluation consisted of patient satisfaction, pain evaluation (visual analog
      scale [VAS]), American Orthopaedic Foot and Ankle Society (AOFAS) ankle score,
      sports activity score, range of motion, the radiological evaluation of magnetic
      resonance imaging (MRI), and single photon emission computed tomography-computed
      tomography (SPECT-CT) analysis of both the ankle and the knee joint. RESULTS:
      Twelve of 21 patients (mean age, 43 years; male, 8; female, 4) were available for
      latest follow-up (mean, 72 months). At follow-up, patients reported a
      satisfaction rate of good to excellent in 92% (n = 11) and poor in 8% (n = 1).
      The average VAS pain score was 3.9 (preoperative, 5.9; P = .02), AOFAS ankle
      score significantly increased from 45.9 to 80.2 points (P < .0001), sports
      activity score remained significantly decreased with 1.25 (preinjury level, 2.3;
      P = .035), and ankle dorsiflexion was significantly reduced (P = .003). Knee pain
      was reported in 6 patients (50%). Radiologically, recurrent lesions were found in
      10 of 10 cases (100%) and some degree of cartilage degeneration and discontinuity
      of the subchondral bone plate in 100%. CONCLUSION: Indications for mosaicplasty
      with a plug transfer from the knee to the talus must be considered carefully, as
      at midterm, moderate outcome and considerable donor-site morbidity may be found.

PMID- 19841141
TI  - A comparative analysis of 7.0-Tesla magnetic resonance imaging and histology
      measurements of knee articular cartilage in a canine posterolateral knee injury
      model: a preliminary analysis.
AB  - BACKGROUND: There has recently been increased interest in the use of 7.0-T
      magnetic resonance imaging for evaluating articular cartilage degeneration and
      quantifying the progression of osteoarthritis. PURPOSE: The purpose of this study
      was to evaluate articular cartilage cross-sectional area and maximum thickness in
      the medial compartment of intact and destabilized canine knees using 7.0-T
      magnetic resonance images and compare these results with those obtained from the
      corresponding histologic sections. STUDY DESIGN: Controlled laboratory study.
      METHODS: Five canines had a surgically created unilateral grade III
      posterolateral knee injury that was followed for 6 months before euthanasia. The
      opposite, noninjured knee was used as a control. At necropsy, 3-dimensional
      gradient echo images of the medial tibial plateau of both knees were obtained
      using a 7.0-T magnetic resonance imaging scanner. Articular cartilage area and
      maximum thickness in this site were digitally measured on the magnetic resonance
      images. The proximal tibias were processed for routine histologic analysis with
      hematoxylin and eosin staining. Articular cartilage area and maximum thickness
      were measured in histologic sections corresponding to the sites of the magnetic
      resonance slices. RESULTS: The magnetic resonance imaging results revealed an
      increase in articular cartilage area and maximum thickness in surgical knees
      compared with control knees in all specimens; these changes were significant for
      both parameters (P <.05 for area; P <.01 for thickness). The average increase in
      area was 14.8% and the average increase in maximum thickness was 15.1%. The
      histologic results revealed an average increase in area of 27.4% (P = .05) and an
      average increase in maximum thickness of 33.0% (P = .06). Correlation analysis
      between the magnetic resonance imaging and histology data revealed that the area
      values were significantly correlated (P < .01), but the values for thickness
      obtained from magnetic resonance imaging were not significantly different from
      the histology sections (P > .1). CONCLUSION: These results demonstrate that 7.0-T
      magnetic resonance imaging provides an alternative method to histology to
      evaluate early osteoarthritic changes in articular cartilage in a canine model by
      detecting increases in articular cartilage area. CLINICAL RELEVANCE: The
      noninvasive nature of 7.0-T magnetic resonance imaging will allow for in vivo
      monitoring of osteoarthritis progression and intervention in animal models and
      humans for osteoarthritis.

PMID- 19841142
TI  - Use of a type I/III bilayer collagen membrane decreases reoperation rates for
      symptomatic hypertrophy after autologous chondrocyte implantation.
AB  - BACKGROUND: Autologous chondrocyte implantation is associated with a high rate of
      reoperation, mostly due to hypertrophy of the periosteal patch. European studies
      investigating the use of collagen membranes as a periosteal substitute report
      significant decreases in reoperation rates to less than 5%. This multicenter
      study investigates the off-label use of 1 collagen membrane as a periosteal
      substitute for autologous chondrocyte implantation. HYPOTHESIS: The use of a
      collagen membrane for autologous chondrocyte implantation will decrease
      reoperation rates for hypertrophy with comparable rates of failure. STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: A multicenter cohort of 300 patients
      treated with periosteal-covered autologous chondrocyte implantation was compared
      with a consecutive series of 101 patients who underwent collagen membrane-covered
      autologous chondrocyte implantation with the Bio-Gide membrane by the same group
      of surgeons. The 1-year hypertrophy-related reoperation rates and overall failure
      rates of autologous chondrocyte implantation were evaluated in both groups.
      RESULTS: Both groups were comparable for age (periosteal autologous chondrocyte
      implantation, 31.9 years; collagen autologous chondrocyte implantation, 32.4
      years; P = .8) and average defect size (4.6 cm(2) and 4.7 cm(2), respectively; P
      = .7). The average number of defects (1.5 and 1.8; P = .001) and total defect
      area per knee (6.7 cm(2) and 8.6 cm(2); P = .003) were larger in the collagen
      membrane group. Within 1 year of surgery, 25.7% of patients treated with
      periosteal-covered autologous chondrocyte implantation required reoperation for
      hypertrophy and 2.3% were considered to have failed their treatment with
      autologous chondrocyte implantation. In comparison, only 5% of patients required
      reoperation for hypertrophy after collagen membrane-covered autologous
      chondrocyte implantation, and 4% were considered treatment failures. CONCLUSION:
      The use of a collagen membrane for autologous chondrocyte implantation decreased
      the reoperation rate for hypertrophy after autologous chondrocyte implantation
      from 25.7% to 5% (P < .0001). Overall 1-year failure rates were comparable
      between the groups (P = .2). Even though the use of a collagen membrane for
      autologous chondrocyte implantation constitutes an off-label indication, its
      application appears justified by the lower morbidity to patients and decreased
      cost to the health care system. A detailed discussion with the patient is
      required regarding the use of an off-label device.

PMID- 19841143
TI  - Assessment of the in vitro kinetic activity of caspofungin against Candida
      glabrata.
AB  - Echinocandins have become the drug of choice in infections caused by Candida
      glabrata. The objective of this study was to evaluate the in vitro activity of
      caspofungin alone and in combination against C. glabrata. In vitro assays
      demonstrated that caspofungin alone showed excellent fungicidal activity against
      C. glabrata, including fluconazole-resistant strains. The combination of
      caspofungin and azole antifungals showed potential synergy against C. glabrata.
      Overall, caspofungin demonstrated excellent in vitro activity, alone and in
      combination, against strains of C. glabrata.

PMID- 19841144
TI  - In vitro activity of thimerosal against ocular pathogenic fungi.
AB  - The in vitro activity of thimerosal versus those of amphotericin B and natamycin
      was assessed against 244 ocular fungal isolates. The activity of thimerosal
      against Fusarium spp., Aspergillus spp., and Alternaria alternata was 256 times,
      512 times, and 128 times, respectively, greater than that of natamycin and 64
      times, 32 times, and 32 times, respectively, greater than that of amphotericin B.
      Thimerosal's antifungal activity was significantly superior to those of
      amphotericin B and natamycin against ocular pathogenic fungi in vitro.

PMID- 19841145
TI  - In vivo activities of recombinant divercin V41 and its structural variants
      against Listeria monocytogenes.
AB  - Recombinant divercin RV41 (DvnRV41) and its structural variants were used in this
      study to assess their antilisterial activities in vivo in mice challenged
      intravenously with Listeria monocytogenes EGDe. Treatment with DvnRV41 before and
      after infection permitted a conclusion as to the capacities of this peptide to
      retain activity and reduce growth of L. monocytogenes EGDe. Moreover, the use of
      structural variants for the first time in vivo and the reductions of their
      activities confirmed the importance of certain amino acids in antilisterial
      activity.

PMID- 19841146
TI  - Patients with long-term oral carriage harbor high-persister mutants of Candida
      albicans.
AB  - Fungal biofilms produce a small number of persister cells which can tolerate high
      concentrations of fungicidal agents. Persisters form upon attachment to a
      surface, an important step in the pathogenesis of Candida strains. The periodic
      application of antimicrobial agents may select for strains with increased levels
      of persister cells. In order to test this possibility, 150 isolates of Candida
      albicans and C. glabrata were obtained from cancer patients who were at high risk
      for the development of oral candidiasis and who had been treated with topical
      chlorhexidine once a day. Persister levels were measured by exposing biofilms
      growing in the wells of microtiter plates to high concentrations of amphotericin
      B and plating for survivors. The persister levels of the isolates varied from 0.2
      to 9%, and strains isolated from patients with long-term carriage had high levels
      of persisters. High-persister strains were isolated from every patient with
      Candida carriage of more than 8 consecutive weeks but from no patients with
      transient carriage. All of the high-persister isolates had an amphotericin B MIC
      that was the same as that for the wild type, indicating that these strains were
      drug-tolerant rather than drug-resistant mutants. Biofilms of the majority of
      high-persister strains also showed an increased tolerance to chlorhexidine and
      had the same MIC for this antimicrobial as the wild type. This study suggests
      that persister cells are clinically relevant, and antimicrobial therapy selects
      for high-persister strains in vivo. The drug tolerance of persisters may be a
      critical but overlooked component responsible for antimicrobial drug failure and
      relapsing infections.

PMID- 19841147
TI  - In vitro activity of mirincamycin (U24729A) against Plasmodium falciparum
      isolates from Gabon.
AB  - We assessed the in vitro activity of mirincamycin, a lincosamide antibiotic,
      against Plasmodium falciparum clinical isolates from Gabon. Growth was determined
      by HRP2 enzyme-linked immunosorbent assay using an adapted protocol with a
      prolonged incubation time (6 days) to account for antibiotic-induced delayed
      death. Mirincamycin's cis and trans isomers are more active (median 50%
      inhibitory concentrations [IC(50)s], 3.2 nM and 2.6 nM) than the comparator drugs
      clindamycin (IC(50), 12 nM) and doxycycline (IC(50), 720 nM), and therefore,
      further clinical development is promising.

PMID- 19841148
TI  - Continuous clindamycin infusion, an innovative approach to treating bone and
      joint infections.
AB  - The feasibility, safety, and efficacy of prolonged, continuous, intravenous
      clindamycin therapy were retrospectively evaluated for 70 patients treated for
      bone and joint infections, 40% of whom were treated as outpatients. The median
      treatment duration was 40 days, the median daily clindamycin dose was 2,400 mg,
      and three moderate-grade adverse events occurred. The median serum clindamycin
      concentrations on days 3 to 14 and days 8 to 28 were 5 and 6.2 mg/liter,
      respectively; the median concentration was significantly lower (P < 0.02) in
      patients treated with rifampin (5.3 mg/liter) than in those not treated with
      rifampin (8.9 mg/liter). Among 53 patients with a median follow-up of 30 months
      (range, 24 to 53 months), 49 (92%) were considered cured (1 patient had a
      relapse, and 3 patients had reinfections).

PMID- 19841149
TI  - Pharmacokinetics of artemether-lumefantrine and artesunate-amodiaquine in
      children in Kampala, Uganda.
AB  - The World Health Organization recommends the use of artemisinin-based combination
      therapies (ACTs) for the treatment of uncomplicated malaria. The two most widely
      adopted ACT regimens are artemether (AR)-lumefantrine (LR) (the combination is
      abbreviated AL) and amodiaquine (AQ)-artesunate (AS). Pharmacokinetic (PK) data
      informing the optimum dosing of these drug regimens is limited, especially in
      children. We evaluated PK parameters in Ugandan children aged 5 to 13 years with
      uncomplicated malaria treated with AL (n = 20) or AQ-AS (n = 21), with intensive
      venous sampling occurring at 0, 2, 4, 8, 24, and 120 h following administration
      of the last dose of 3-day regimens of AL (twice daily) or AQ-AS (once daily). AS
      achieved an estimated maximum concentration in plasma (C(max)) of 51 ng/ml and an
      area under the concentration-time curve from time zero to infinity (AUC(0
      infinity)) of 113 ng.h/ml; and its active metabolite, dihydroartemisinin (DHA),
      achieved a geometric mean C(max) of 473 ng/ml and an AUC(0-infinity) of 1,404
      ng.h/ml. AR-DHA exhibited a C(max) of 34/119 ng/ml and an AUC(0-infinity) of
      168/382 ng.h/ml, respectively. For LR, C(max) and AUC(0-infinity) were 6,757
      ng/ml and 210 microg.h/ml, respectively. For AQ and its active metabolite,
      desethylamodiaquine (DEAQ), the C(max)s were 5.2 ng/ml and 235 ng/ml,
      respectively, and the AUC(0-infinity)s were 39.3 ng.h/ml and 148 microg.h/ml,
      respectively. Comparison of the findings of the present study to previously
      published data for adults suggests that the level of exposure to LR is lower in
      children than in adults and that the level of AQ-DEAQ exposure is similar in
      children and adults. For the artemisinin derivatives, differences between
      children and adults were variable and drug specific. The PK results generated for
      children must be considered to optimize the dosing strategies for these widely
      utilized ACT regimens.

PMID- 19841150
TI  - Molecular correlates of high-level antifolate resistance in Rwandan children with
      Plasmodium falciparum malaria.
AB  - Antifolate drugs have an important role in the treatment of malaria.
      Polymorphisms in the genes encoding the dihydrofolate reductase and
      dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa
      drugs, respectively. Rwanda has the highest levels of antimalarial drug
      resistance in Africa. We correlated the efficacy of chlorproguanil-dapsone plus
      artesunate (CPG-DDS+A) and amodiaquine plus sulfadoxine-pyrimethamine (AQ+SP) in
      children with uncomplicated malaria caused by Plasmodium falciparum parasites
      with pfdhfr and pfdhps mutations, which are known to confer reduced drug
      susceptibility, in two areas of Rwanda. In the eastern province, where the cure
      rates were low, over 75% of isolates had three or more pfdhfr mutations and two
      or three pfdhps mutations and 11% had the pfdhfr 164-Leu polymorphism. In the
      western province, where the cure rates were significantly higher (P < 0.001), the
      prevalence of multiple resistance mutations was lower and the pfdhfr I164L
      polymorphism was not found. The risk of treatment failure following the
      administration of AQ+SP more than doubled for each additional pfdhfr resistance
      mutation (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.01 to 5.55; P =
      0.048) and each pfdhps mutation (OR = 2.1; 95% CI = 1.21 to 3.54; P = 0.008). The
      risk of failure following CPG-DDS+A treatment was 2.2 times higher (95% CI = 1.34
      to 3.7) for each additional pfdhfr mutation, whereas there was no association
      with mutations in the pfdhps gene (P = 0.13). The pfdhfr 164-Leu polymorphism is
      prevalent in eastern Rwanda. Antimalarial treatments with currently available
      antifol-sulfa combinations are no longer effective in Rwanda because of high
      level resistance.

PMID- 19841151
TI  - Efficacy of posaconazole in a murine disseminated infection by Candida
      tropicalis.
AB  - We evaluated the efficacy of posaconazole against Candida tropicalis in a
      systemic infection model with immunosuppressed mice. Posaconazole at 50 mg/kg of
      body weight/day prolonged the survival of mice and reduced the fungal tissue
      burden of mice infected with any of the five strains tested, with the exception
      of one strain that had a high MIC against this drug. Our results demonstrate the
      efficacy of posaconazole in the treatment of invasive murine infection caused by
      C. tropicalis.

PMID- 19841152
TI  - Attributable hospital cost and length of stay associated with health care
      associated infections caused by antibiotic-resistant gram-negative bacteria.
AB  - Determination of the attributable hospital cost and length of stay (LOS) are of
      critical importance for patients, providers, and payers who must make rational
      and informed decisions about patient care and the allocation of resources. The
      objective of the present study was to determine the additional total hospital
      cost and LOS attributable to health care-associated infections (HAIs) caused by
      antibiotic-resistant, gram-negative (GN) pathogens. A single-center,
      retrospective, observational comparative cohort study was performed. The study
      involved 662 patients admitted from 2000 to 2008 who developed HAIs caused by one
      of following pathogens: Acinetobacter spp., Enterobacter spp., Escherichia coli,
      Klebsiella spp., or Pseudomonas spp. The attributable total hospital cost and LOS
      for HAIs caused by antibiotic-resistant GN pathogens were determined by
      comparison with the hospital costs and LOS for a control group with HAIs due to
      antibiotic-susceptible GN pathogens. Statistical analyses were conducted by using
      univariate and multivariate analyses. Twenty-nine percent of the HAIs were caused
      by resistant GN pathogens, and almost 16% involved a multidrug-resistant GN
      pathogen. The additional total hospital cost and LOS attributable to antibiotic
      resistant HAIs caused by GN pathogens were 29.3% (P < 0.0001; 95% confidence
      interval, 16.23 to 42.35) and 23.8% (P = 0.0003; 95% confidence interval, 11.01
      to 36.56) higher than those attributable to HAIs caused by antibiotic-susceptible
      GN pathogens, respectively. Significant covariates in the multivariate analysis
      were age >or=12 years, pneumonia, intensive care unit stay, and neutropenia. HAIs
      caused by antibiotic-resistant GN pathogens were associated with significantly
      higher total hospital costs and increased LOSs compared to those caused by their
      susceptible counterparts. This information should be used to assess the potential
      cost-efficacy of interventions aimed at the prevention of such infections.

PMID- 19841154
TI  - SmQnr contributes to intrinsic resistance to quinolones in Stenotrophomonas
      maltophilia.

PMID- 19841153
TI  - Inducible APOBEC3G-Vif double stable cell line as a high-throughput screening
      platform to identify antiviral compounds.
AB  - Inhibition of the interaction of the human cytidine-deaminase APOBEC3G (A3G) with
      the human immunodeficiency virus (HIV) type 1-specific viral infectivity factor
      (Vif) represents a novel therapeutic approach in which a cellular factor with
      potent antiviral activity (A3G) plays a key role. In HIV-infected cells, the
      interaction of Vif with A3G leads to the subsequent degradation of A3G by the 26S
      proteasome via the ubiquitin pathway and to the loss of antiviral activity. To
      establish a stable and convenient cellular testing platform for the high
      throughput screening of potential antiviral compound libraries, we engineered a
      double transgenic cell line constitutively expressing an enhanced yellow
      fluorescent protein expressor (EYFP-A3G) fusion as well as a Tet-Off controllable
      Vif protein. With this cell line, we were able to measure precisely the Vif
      induced degradation of A3G in the presence of potential antiviral compounds in an
      easy-to-handle, robust, and practical high-throughput multiwell plate format with
      an excellent screening window coefficient (Z factor) of 0.67.

PMID- 19841155
TI  - MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease.
AB  - The administration of hepatitis C virus (HCV) NS3/4A protease inhibitors to
      patients with chronic HCV infections has demonstrated that they have dramatic
      antiviral effects and that compounds acting via this mechanism are likely to form
      a key component of future anti-HCV therapy. We report here on the preclinical
      profile of MK-7009, an inhibitor of genotype 1a and 1b proteases at subnanomolar
      concentrations with modestly shifted potency against genotype 2a and 2b proteases
      at low nanomolar concentrations. Potent activity was also observed in a cell
      based HCV replicon assay in the presence of added human serum (50%). In multiple
      species evaluated in preclinical studies, the MK-7009 concentrations in the liver
      were maintained at a significant multiple of the cell-based replicon 50%
      effective concentration over 12 to 24 h following the administration of moderate
      oral doses (5 to 10 mg per kg of body weight). MK-7009 also had excellent
      selectivity against both a range of human proteases and a broad panel of
      pharmacologically relevant ion channels, receptors, and enzymes. On the basis of
      this favorable profile, MK-7009 was selected for clinical development and is
      currently being evaluated in controlled clinical trials with both healthy
      volunteers and HCV-infected patients.

PMID- 19841157
TI  - Systemic bioavailability of topical diclofenac sodium gel 1% versus oral
      diclofenac sodium in healthy volunteers.
AB  - Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1%
      were compared with those of oral diclofenac sodium 50-mg tablets. In a
      randomized, 3-way crossover study, healthy volunteers (n = 40) received three 7
      day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g
      on surface area 400 cm(2)), (B) 48 g gel applied as 4 g per knee 4 times daily to
      2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200
      cm(2)), and (C) 150 mg oral diclofenac applied as 50-mg tablets 3 times daily.
      Thirty-nine participants completed all 3 regimens. Systemic exposure was greater
      with oral diclofenac (AUC(0-24), 3890 +/- 1710 ng x h/mL) than with topical
      treatments A (AUC(0-24), 233 +/- 128 ng x h/mL) and B (AUC(0-24), 807 +/- 478 ng
      x h/mL). Oral diclofenac inhibited platelet aggregation, cyclooxygenase-1 (COX
      1), and COX-2. Topical diclofenac did not inhibit platelet aggregation and
      inhibited COX-1 and COX-2 less than oral diclofenac. Treatment-related adverse
      events were mild and limited to application site reactions with diclofenac sodium
      gel 1% (n = 4) and gastrointestinal reactions with oral diclofenac (n = 3).
      Systemic exposure with diclofenac sodium gel 1% was 5- to 17-fold lower than with
      oral diclofenac. Systemic effects with topical diclofenac were less pronounced.

PMID- 19841156
TI  - Effect of age, weight, and CYP2C19 genotype on escitalopram exposure.
AB  - The purpose of this study was to characterize escitalopram population
      pharmacokinetics (PK) in patients treated for major depression in a cross
      national, US-Italian clinical trial. Data from the 2 sites participating in this
      trial, conducted at Pittsburgh (United States) and Pisa (Italy), were used.
      Patients received 5, 10, 15, or 20 mg of escitalopram daily for a minimum of 32
      weeks. Nonlinear mixed effects modeling was used to model the PK characteristics
      of escitalopram. One- and 2-compartment models with various random effect
      implementations were evaluated during model development. Objective function
      values and goodness-of-fit plots were used as model selection criteria. CYP2C19
      genotype, age, weight, body mass index, sex, race, and clinical site were
      evaluated as possible covariates. In total, 320 plasma concentrations from 105
      Pittsburgh patients and 153 plasma concentrations from 67 Pisa patients were
      available for the PK model development. A 1-compartmental model with linear
      elimination and proportional error best described the data. Apparent clearance
      (CL/F) and volume of distribution (V/F) for escitalopram without including any
      covariates in the patient population were 23.5 L/h and 884 L, respectively.
      CYP2C19 genotype, weight, and age had a significant effect on CL/F, and patient
      body mass index affected estimated V/F. Patients from Pisa, Italy, had
      significantly lower clearances than patients from Pittsburgh that disappeared
      after controlling for patient CYP2C19 genotype, age, and weight. Postprocessed
      individual empirical Bayes estimates on clearance for the 172 patients show that
      patients without allele CYP2C19(*)2 or (*)3 (n = 82) cleared escitalopram 33.7%
      faster than patients with heterogeneous or homogeneous (*)2 or (*)3 ((*)17/(*)2,
      (*)17/(*)3, (*)1/(*)2, (*)1/(*)3, (*)2/(*)2, (*)2/(*)3, and (*)3/(*)3, n = 46).
      CL/F significantly decreased with increasing patient age. Patients younger than
      30 years (n = 45) cleared escitalopram 20.7% and 42.7% faster than patients aged
      30 to 50 years (n = 84) and older than 50 years of age (n = 43), respectively.
      CYP2C19 genotype, age, and weight strongly influenced the CL/F of escitalopram.
      These variables may affect patient tolerance of this antidepressant and may
      provide important information in the effort to tailor treatments to patients'
      individual needs.

PMID- 19841158
TI  - Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients
      with chronic hepatitis C.
AB  - Silymarin, derived from the milk thistle plant Silybum marianum, is widely used
      for self-treatment of liver diseases, including hepatitis C virus (HCV), and its
      antiviral activity has been demonstrated in vitro and in HCV patients
      administered an intravenous formulation of the major silymarin flavonolignans,
      silybin A and silybin B. The safety and dose-exposure relationships of higher
      than customary oral doses of silymarin and its acute effects on serum HCV RNA
      were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well
      compensated, chronic noncirrhotic HCV who failed interferon-based therapy were
      randomized 3:1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg
      silymarin were administered every 8 hours for 7 days. Steady-state exposures for
      silybin A and silybin B increased 11-fold and 38-fold, respectively, with a 5
      fold increase in dose, suggesting nonlinear pharmacokinetics. No drug-related
      adverse events were reported, and no clinically meaningful reductions from
      baseline serum transaminases or HCV RNA titer were observed. Oral doses of
      silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear
      pharmacokinetics of silybin A and silybin B suggests low bioavailability
      associated with customary doses of silymarin may be overcome with doses above 700
      mg.

PMID- 19841159
TI  - Itraconazole and rifampin alter significantly the disposition and antihistamine
      effect of ebastine and its metabolites in healthy participants.
AB  - The present study was performed to elucidate the effects of itraconazole and
      rifampin on the pharmacokinetics and pharmacodynamics of ebastine, a nonsedative
      H1 receptor antagonist. In a 3-way crossover sequential design with 2-week
      washouts, 10 healthy participants were pretreated with itraconazole for 6 days,
      rifampin for 10 days, or neither. After oral administration of 20 mg ebastine,
      blood and urine samples were collected for 72 and 24 hours, respectively, and
      histamine-induced wheal and flare reactions were measured to assess the
      antihistamine response for 12 hours. Itraconazole pretreatment decreased the oral
      clearance of ebastine to 10% (P < .001) and increased the AUC(infinity) of the
      active metabolite, carebastine, by 3-fold (P < .001). On the other hand, rifampin
      pretreatment decreased the AUC(infinity) of carebastine to 15% (P < .001), with
      an enormous reduction in the oral bioavailability of ebastine and significantly
      reduced histamine-induced skin reactions. From these results, the disposition of
      ebastine and carebastine seems to be significantly altered by coadministration of
      itraconazole or rifampin. The antihistamine response after ebastine dosing would
      be decreased following rifampin pretreatments.

PMID- 19841160
TI  - Specific and pronounced impacts of lisinopril and lisinopril plus simvastatin on
      erythrocyte antioxidant enzymes.
AB  - Angiotensin-converting enzyme inhibitors are effective at reducing blood
      pressure, whereas statins decrease plasma cholesterol impeding atherosclerosis.
      It is hypothesized that these medications may improve blood pressure and serum
      cholesterol by modifying the antioxidative status and energy metabolism of
      erythrocytes. In this study, the effects of 2 treatments are compared: lisinopril
      alone versus lisinopril + simvastatin, on erythrocyte antioxidant and energy
      metabolic enzymes. Patients with atherosclerosis and moderate hypertension are
      randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d
      plus simvastatin 20 mg/d for 24 weeks. Higher catalase activity and lower
      glutathione peroxidase activity are observed in 94% to 100% patients from both
      groups after 12 and 24 weeks of treatment. Superoxide dismutase activity is
      increased significantly only after 24 weeks. No changes of glutathione reductase,
      lactate dehydrogenase, and phosphofructokinase activities are found under any
      conditions indicated. Both treatments decrease systolic and diastolic blood
      pressure equally. Only lisinopril + simvastatin treatment decreases plasma total
      cholesterol and low-density lipoprotein cholesterol. The results show for the
      first time that lisinopril monotherapy and combined lisinopril + simvastatin
      therapy exhibit specific and pronounced effects on antioxidant and energy
      metabolic enzyme activities in erythrocytes of hypertensive patients.

PMID- 19841161
TI  - No pharmacokinetic interaction between lacosamide and carbamazepine in healthy
      volunteers.
AB  - Lacosamide is a new antiepileptic drug for adjunctive treatment of adult partial
      onset seizures. Two open-label, multiple-dose clinical trials were conducted to
      evaluate the potential for pharmacokinetic interaction between lacosamide and
      carbamazepine. The influence of carbamazepine on lacosamide pharmacokinetics
      (trial A) and lacosamide on carbamazepine pharmacokinetics (trial B) was
      investigated in 19 (trial A) and 18 (trial B) healthy male participants. Trial A
      participants received lacosamide 200 mg bid alone and with carbamazepine 200 mg
      bid. Trial B participants received carbamazepine 200 mg bid alone and with
      lacosamide 200 mg bid. Pharmacokinetic parameters, area under the concentration
      time curve during a dosage interval at steady state (AUC(tau,ss)), and maximum
      steady-state plasma drug concentration during a dosage interval (C(max,ss)) of
      lacosamide, carbamazepine, and carbamazepine-10,11-epoxide were measured and
      compared for each drug alone and together. The AUC(tau,ss) and C(max,ss) point
      estimates (combined vs sole treatment) showed relative bioavailability of
      approximately 100% for both drugs. All 90% confidence intervals of AUC(tau,ss)
      and C(max,ss) were within the generally accepted bioequivalence ranges of 80% to
      125%. No changes in rate or extent of absorption or terminal half-life were
      observed. These results suggest that lacosamide and carbamazepine have a low
      potential for pharmacokinetic drug-drug interaction in clinical use.

PMID- 19841162
TI  - FROUNT is a common regulator of CCR2 and CCR5 signaling to control directional
      migration.
AB  - FROUNT is a known CCR2-binding protein that facilitates monocyte/macrophage
      infiltration. Here we report that FROUNT also binds to the C-terminal region of
      CCR5 and enhances CCR5-mediated cellular chemotaxis. We show that FROUNT
      overexpression enhances the directionality of chemotaxis, while FROUNT
      suppression results in impaired responsiveness. Furthermore, we found an increase
      in consolidated pseudopodium formation in FROUNT-overexpressing cells (FNT cells)
      on uniform stimulation with CCL4 (MIP1-beta), a specific ligand of CCR5. In most
      FNT cells, one to two pseudopodia directed toward higher chemokine concentration
      were found, whereas most FNT-suppressed cells had multiple pseudopodia. The data
      indicate that FROUNT is involved in sensing and amplifying a shallow
      extracellular chemokine gradient that leads to a limited number of accurate
      pseudopodia directed toward the chemokine concentration. In addition to its
      separate roles in CCR2- and CCR5-mediated chemotaxis, FROUNT, as a common
      regulator of these receptors, possibly plays a crucial role in the recruitment of
      immune cells expressing these receptors.

PMID- 19841163
TI  - IDO mediates TLR9-driven protection from experimental autoimmune diabetes.
AB  - Originally predicated on the recognition of an increasing prevalence of allergy,
      the hygiene hypothesis was later found to accommodate the contrasting
      epidemiologic trends in developed countries for infectious vs autoimmune
      diseases. Experimentally, reduced exposure to infections will increase the risk
      of disease in several models of experimental autoimmunity. Although TLRs were
      initially considered as stimulatory molecules capable of activating early defense
      mechanisms against invading pathogens, emerging data suggest that they can also
      exert a regulatory function. In the present study, we evaluated whether TLR3 and
      TLR9, recognizing microbial dsDNA and CpG-containing DNA sequences, respectively,
      play a role in the protection from experimental autoimmune diabetes induced in
      C57BL/6 mice by streptozotocin. In wild-type animals, the disease was accompanied
      by up-regulation of IDO in pancreatic lymph nodes and would be greatly
      exacerbated by in vivo administration of an IDO inhibitor. Conversely,
      administration of a CpG-containing oligodeoxynucleotide greatly attenuated the
      disease in an IDO-dependent fashion. TLR9-, but not TLR3-deficient mice developed
      a more robust disease, an event accompanied by lack of IDO induction in
      pancreatic lymph nodes. Thus, our data suggest that the TLR9-IDO axis may
      represent a valuable target in the prevention/therapy of type 1 diabetes.

PMID- 19841164
TI  - Ligand binding but undetected functional response of FcR after their capture by T
      cells via trogocytosis.
AB  - Intercellular transfer of cell surface proteins by trogocytosis is common and
      could affect T cell responses. Yet, the role of trogocytosis in T cell function
      is still elusive, and it is unknown whether a molecule, once captured by T cells,
      harbors the same biological properties as in donor APC. In this study, we showed
      that FcgammaR as well as the associated FcRgamma subunit could be detected at
      high levels on murine and human T cells after their intercellular transfer from
      FcgammaR-expressing APC. Capture of FcgammaR occurred during coculture of T cells
      with FcgammaR-expressing APC upon Ab- or Ag-mediated T cell stimulation. Once
      captured by T cells, FcgammaR were expressed in a conformation compatible with
      physiological function and conferred upon T cells the ability to bind immune
      complexes and to provision B cells with this source of Ag. However, we were
      unable to detect downstream signal or signaling-dependent function following the
      stimulation of FcgammaR captured by T cells, and biochemical studies suggested
      the improper integration of FcgammaR in the recipient T cell membrane. Thus, our
      study demonstrates that T cells capture FcgammaR that can efficiently exert
      ligand-binding activity, which, per se, could have functional consequences in T
      cell-B cell cooperation.

PMID- 19841165
TI  - Thymic regulation of autoimmune disease by accelerated differentiation of Foxp3+
      regulatory T cells through IL-7 signaling pathway.
AB  - The exact role of adult thymus in autoimmune disease state is poorly understood.
      We show here that thymus regulated experimental autoimmune encephalomyelitis
      (EAE), an animal model for multiple sclerosis, as evidenced by loss of
      spontaneous recovery in thymectomized EAE mice. There was progressive enrichment
      for CD4 single-positive Foxp3(+) regulatory T cells in thymocytes during the
      course of EAE and they suppressed the disease when adoptively transferred. Thymus
      was shown to undergo an active process characterized by accelerated
      differentiation and proliferation of regulatory T (Treg) cells through a
      mechanism involving increased expression of IL-7 in stromal cells and dynamic
      expression of IL-7 receptor in thymic Treg cells. This process preceded EAE
      recovery and selectively affected Treg over non-Treg cells in the thymus, leading
      to increased output of thymic Treg cells and self-regulation of EAE. The study
      reveals a novel role of thymus in self-regulation of autoimmune condition.

PMID- 19841166
TI  - IL-33 amplifies the polarization of alternatively activated macrophages that
      contribute to airway inflammation.
AB  - Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity.
      Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL
      33, have impaired type 2 immune responses. We therefore reasoned that IL-33/ST2
      signaling may be involved in the differentiation and activation of AAM during
      airway inflammation. We report here that IL-33 changed the quiescent phenotype of
      alveolar macrophages toward an AAM phenotype that expressed mannose receptor, IL
      4Ralpha, and produced high levels of CCL24 and CCL17 in an IL-13-dependent manner
      during IL-33-induced airway inflammation. Neutralization of AAM-derived CCL24 led
      to an amelioration of IL-33-induced eosinophilia in the lungs. Moreover,
      depletion of alveolar macrophages reduced IL-33-induced airway inflammation.
      Additionally, the attenuated OVA-induced airway inflammation in ST2(-/-) mice was
      associated with a decrease in AAM differentiation. In vitro, IL-33 amplified IL
      13-induced polarization of alveolar- and bone marrow-derived macrophage toward an
      AAM phenotype by increasing the expression of arginase I, Ym1, as well as the
      production of CCL24 and CCL17. IL-13/IL-4Ralpha signaling was crucial for IL-33
      driven AAM amplification by inducing the expression of ST2L. Finally, we showed
      that IL-33 was more abundantly expressed in the lung epithelial cells of asthma
      patients than those from healthy controls, suggesting that IL-33 may be involved
      in lung macrophage activation in clinical asthma. Taken together, we demonstrate
      here that IL-33/ST2 plays a significant role in the amplification of AAM
      polarization and chemokine production which contribute to innate and Ag-induced
      airway inflammation.

PMID- 19841167
TI  - Potent high-affinity antibodies for treatment and prophylaxis of respiratory
      syncytial virus derived from B cells of infected patients.
AB  - Native human Abs represent attractive drug candidates; however, the low frequency
      of B cells expressing high-quality Abs has posed a barrier to discovery. Using a
      novel single-cell phenotyping technology, we have overcome this barrier to
      discover human Abs targeting the conserved but poorly immunogenic central motif
      of respiratory syncytial virus (RSV) G protein. For the entire cohort of 24
      subjects with recent RSV infection, B cells producing Abs meeting these stringent
      specificity criteria were rare, <10 per million. Several of the newly cloned Abs
      bind to the RSV G protein central conserved motif with very high affinity (K(d) 1
      24 pM). Two of the Abs were characterized in detail and compared with
      palivizumab, a humanized mAb against the RSV F protein. Relative to palivizumab,
      the anti-G Abs showed improved viral neutralization potency in vitro and enhanced
      reduction of infectious virus in a prophylaxis mouse model. Furthermore, in a
      mouse model for postinfection treatment, both anti-G Abs were significantly more
      effective than palivizumab at reducing viral load. The combination of activity in
      mouse models for both prophylaxis and treatment makes these high-affinity human
      derived Abs promising candidates for human clinical testing.

PMID- 19841168
TI  - Mcl-1-mediated impairment of the intrinsic apoptosis pathway in circulating
      neutrophils from critically ill patients can be overcome by Fas stimulation.
AB  - The systemic inflammatory response syndrome and subsequent organ failure are
      mainly driven by activated neutrophils with prolonged life span, which is
      believed to be due to apoptosis resistance. However, detailed underlying
      mechanisms leading to neutrophil apoptosis resistance are largely unknown, and
      possible therapeutic options to overcome this resistance do not exist. Here we
      report that activated neutrophils from severely injured patients exhibit cell
      death resistance due to impaired activation of the intrinsic apoptosis pathway,
      as evidenced by limited staurosporine-induced mitochondrial membrane
      depolarization and decreased caspase-9 activity. Moreover, we found that these
      neutrophils express high levels of antiapoptotic Mcl-1 and low levels of
      proapoptotic Bax protein. Mcl-1 up-regulation was dependent on elevated
      concentrations of GM-CSF in patient serum. Accordingly, increased Mcl-1 protein
      stability and GM-CSF serum concentrations were shown to correlate with
      staurosporine-induced apoptosis resistance. However, cross-linking of neutrophil
      Fas by immobilized agonistic anti-Fas IgM resulted in caspase-dependent
      mitochondrial membrane depolarization and apoptosis induction. In conclusion, the
      observed impairment of the intrinsic pathway and the resulting apoptosis
      resistance may be overcome by immobilized agonistic anti-Fas IgM. Targeting of
      neutrophil Fas by immobilized agonistic effector molecules may represent a new
      therapeutic tool to limit neutrophil hyperactivation and its sequelae in patients
      with severe immune disorders.

PMID- 19841169
TI  - Skin melanoma development in ret transgenic mice despite the depletion of
      CD25+Foxp3+ regulatory T cells in lymphoid organs.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) known to mediate self-tolerance
      were also shown to contribute to tumor progression. In mouse melanoma
      transplantation models, Treg depletion resulted in the stimulation of antitumor
      immune responses and tumor eradication. To study Treg in conditions close to the
      clinical situation, we used a ret transgenic mouse spontaneous melanoma model,
      which, in contrast to transplantation models, resembles human melanoma regarding
      clinical development. Significantly higher numbers of Treg were found in skin
      tumors and metastatic lymph nodes at early stages of melanoma progression
      compared with more advanced stages accompanied by the elevated CCR4 expression on
      Treg and higher production of its ligand CCL2 in tumor lesions. Numbers of tumor
      infiltrating Treg inversely correlated with Treg amounts in the bone marrow,
      suggesting their possible recruitment to melanoma lesions from this organ. The
      immunosuppressive function of Treg from transgenic tumor-bearing mice was similar
      to that from transgenic tumor-free mice or nontransgenic littermates. Although
      anti-CD25 mAb injections resulted in the efficient Treg depletion from lymphoid
      organs of transgenic mice, melanoma development was not significantly delayed.
      Furthermore, the treatment of mice with macroscopical tumors also failed to
      inhibit tumor progression, which correlated with the inability to deplete
      intratumoral Treg. We suggest that in the autochthonous melanoma genesis, other
      immunosuppressive cells could play an important role and replace
      immunosuppressive, tumor-promoting functions of Treg. Therefore, effective
      melanoma immunotherapy should include the inhibition of Treg migration into the
      tumor combined with neutralization of other immunosuppressive cells and factors
      in the tumor microenvironment.

PMID- 19841170
TI  - Responsiveness of stromal fibroblasts to IFN-gamma blocks tumor growth via
      angiostasis.
AB  - The importance of stromal cells for tumor is akin to soil for seed. However, the
      interaction among these cells is far from understood. In this study, we show that
      stromal fibroblasts exist not only during tumor progression but also during
      regression stage, together with immune effector cells. Coinjection of stromal
      fibroblasts with tumor cells often promotes tumor growth. However, the presence
      of IFN-gamma significantly impairs the ability of these cells to promote tumor
      growth due to a reduced angiogenesis. The mechanism relies mainly on the IFN
      gamma-mediated down-regulation of vascular endothelial growth factor production
      by fibroblasts. The results reveal a novel link between immune cells and nonbone
      marrow-derived stromal cells, and define stromal fibroblasts as the main targets
      of IFN-gamma in tumor immunity.

PMID- 19841171
TI  - Anergic T cells are metabolically anergic.
AB  - Full T cell activation requires TCR engagement (signal 1) in the context of
      costimulation (signal 2). Costimulation is required for maximal expression of
      effector cytokines and prevention of T cell anergy. It has become increasingly
      clear that another major function of costimulation is to up-regulate the
      metabolic machinery necessary for T cell function. In this report we demonstrate
      that anergic T cells are metabolically anergic, in that upon full stimulation
      (signals 1 plus 2) they fail to up-regulate the machinery necessary to support
      increased metabolism. These findings suggest that one mechanism responsible for
      the maintenance of T cell anergy is failure to up-regulate the metabolic
      machinery. Furthermore, we demonstrate that by blocking leucine, glucose, and
      energy metabolism, T cell activation is mitigated. Additionally, inhibition of
      these metabolic pathways during T cell activation leads to anergy in Th1
      differentiated cells. Overall, our findings extend the role of T cell metabolism
      in regulating T cell function.

PMID- 19841172
TI  - Analysis of the role of tripeptidyl peptidase II in MHC class I antigen
      presentation in vivo.
AB  - Previous experiments using enzyme inhibitors and RNA interference in cell lysates
      and cultured cells have suggested that tripeptidyl peptidase II (TPPII) plays a
      role in creating and destroying MHC class I-presented peptides. However, its
      precise contribution to these processes has been controversial. To elucidate the
      importance of TPPII in MHC class I Ag presentation, we analyzed TPPII-deficient
      gene-trapped mice and cell lines from these animals. In these mice, the
      expression level of TPPII was reduced by >90% compared with wild-type mice.
      Thymocytes from TPPII gene-trapped mice displayed more MHC class I on the cell
      surface, suggesting that TPPII normally limits Ag presentation by destroying
      peptides overall. TPPII gene-trapped mice responded as well as did wild-type mice
      to four epitopes from lymphocytic choriomeningitis virus. The processing and
      presentation of peptide precursors with long N-terminal extensions in TPPII gene
      trapped embryonic fibroblasts was modestly reduced, but in vivo immunization with
      recombinant lentiviral or vaccinia virus vectors revealed that such peptide
      precursors induced an equivalent CD8 T cell response in wild-type and TPPII
      deficient mice. These data indicate that while TPPII contributes to the trimming
      of peptides with very long N-terminal extensions, TPPII is not essential for
      generating most MHC class I-presented peptides or for stimulating CTL responses
      to several Ags in vivo.

PMID- 19841173
TI  - Generation of B cell memory to the bacterial polysaccharide alpha-1,3 dextran.
AB  - B1b B cells generate a novel form of memory and provide Ab mediated-protection to
      persisting bacterial pathogens. To understand how B1b B cells establish memory to
      polysaccharide Ags, we studied an oligoclonal B cell response to alpha-1,3
      dextran (DEX) expressed on Enterobacter cloacae. B cells specific for DEX enrich
      in the marginal zone (MZ) and B1b B cell populations. After E. cloacae
      immunization, MZ B cells were responsible for the generation of initial peak DEX
      specific Ab titers, whereas, DEX-specific B1b B cells expanded and played an
      important role in boosted production of DEX-specific Ab titers upon E. cloacae
      rechallenge. Cell transfer experiments demonstrate that B1b B cells possess the
      capacity for both robust proliferation and plasma cell differentiation, thus
      distinguishing themselves from MZ B cells, which uniformly commit to plasma cell
      differentiation. These results define B1b B cells as the principal reservoir for
      memory to bacterial-associated polysaccharide Ags.

PMID- 19841174
TI  - Lymph node stromal cells support dendritic cell-induced gut-homing of T cells.
AB  - T cells are imprinted to express tissue-specific homing receptors upon activation
      in tissue-draining lymph nodes, resulting in their migration to the site of Ag
      entry. Expression of gut-homing molecules alpha(4)beta(7) and CCR9 is induced by
      retinoic acid, a vitamin A metabolite produced by retinal dehydrogenases, which
      are specifically expressed in dendritic cells as well as stromal cells in mucosa
      draining lymph nodes. In this study, we demonstrate that mesenteric lymph node
      stromal cell-derived retinoic acid can directly induce the expression of gut
      homing molecules on proliferating T cells, a process strongly enhanced by bone
      marrow-derived dendritic cells in vitro. Therefore, cooperation of sessile lymph
      node stromal cells with mobile dendritic cells warrants the imprinting of tissue
      specific homing receptors on activated T cells.

PMID- 19841176
TI  - TNFR2-deficient memory CD8 T cells provide superior protection against tumor cell
      growth.
AB  - TNF receptor-2 (TNFR2) plays a critical role in promoting the activation and
      survival of naive T cells during the primary response. Interestingly, anti-CD3
      plus IL-2 activated TNFR2(-/-) CD8 T cells are highly resistant to activation
      induced cell death (AICD), which correlates with high expression levels of
      prosurvival molecules such as Bcl-2, survivin, and CD127 (IL-7Ralpha). We
      determined whether the resistance of activated TNFR2(-/-) CD8 T cells to AICD
      contributes to more effective protection against tumor cell growth. We found that
      during a primary tumor challenge, despite initial inferiority in controlling
      tumor cell growth, TNFR2(-/-) mice were able to more effectively control tumor
      burden over time compared with wild-type (WT) mice. Furthermore, vaccination of
      TNFR2(-/-) mice with recombinant Listeria monocytogenes that express OVA confers
      better protection against the growth of OVA-expressing E.G7 tumor cells relative
      to similarly vaccinated WT mice. The enhanced protection against tumor cell
      growth was not due to more effective activation of OVA-specific memory CD8 T
      cells in vaccinated TNFR2(-/-) mice. In vitro studies indicate that optimally
      activated OVA-specific TNFR2(-/-) CD8 T cells proliferated to the same extent and
      possess similar cytotoxicity against E.G7 tumor cells as WT CD8 T cells. However,
      relative to WT cells, activated OVA-specific TNFR2(-/-) CD8 T cells were highly
      resistant to AICD. Thus, the enhanced protection against E.G7 in TNFR2(-/-) mice
      is likely due to the recruitment and activation of OVA-specific memory TNFR2(-/-)
      CD8 T cells and their prolonged survival at the tumor site.

PMID- 19841175
TI  - In vitro responses to avian influenza H5 by human CD4 T cells.
AB  - To address the question of whether human T cells are capable of recognizing novel
      isolates of influenza virus, in vitro responses to recombinant Ags and synthetic
      peptides derived from the sequences of H1, H3, and H5 were examined in a cohort
      of 64 individuals selected from a healthy blood donor population. Humans respond
      in vitro to H1 and H3 following exposure through natural infection and
      vaccination. Responses to H5 were well correlated with those to H1 or H3, and
      thus, a significant repertoire of H5-responsive T cells is present in many
      individuals; clear nonresponders to H1, H3, and H5, however, do exist.
      Differences were observed in the cytokine responses to H1, H3, and H5, whereas
      both IL-2 and IFN-gamma production characteristic of memory responses were
      observed for H1 and H3, and H5-specific responses elicited primarily IL-2 and
      little or no IFN-gamma, consistent with a naive T cell phenotype. Responses to
      all influenza HA were restricted by HLA-DR molecules. To address the structural
      basis for T cell recognition of H1 and H5, overlapping synthetic peptides were
      used to identify epitopes and to determine whether recognition of H5 was limited
      to homologous sequences in H1, the most closely related HA phylogenetically.
      Although responses were generally correlated, no complete structural overlap was
      observed. These results suggest that helper T cell cross reactivity between
      different influenza strains may impart cross-protection to H5N1 strain of
      influenza.

PMID- 19841177
TI  - IL-27 directly restrains lung tumorigenicity by suppressing cyclooxygenase-2
      mediated activities.
AB  - Gene transfer of IL-27 to tumor cells has been proven to inhibit tumor growth in
      vivo by antiproliferation, antiangiogenesis, and stimulation of immunoprotection.
      To investigate the nonimmune mechanism of IL-27 that suppresses lung cancer
      growth, we have established a single-chain IL-27-transduced murine Lewis lung
      carcinoma (LLC-1) cell line (LLC-1/scIL-27) to evaluate its tumorigenic potential
      in vivo. Mice inoculated with LLC/scIL-27 displayed retardation of tumor growth.
      Production of IL-12, IFN-gamma, and cytotoxic T cell activity against LLC-1 was
      manifest in LLC/scIL-27-injected mice. Of note, LLC-1/scIL-27 exhibited decreased
      expression of cyclooxygenase-2 (COX-2) and PGE(2). On the cellular level, the
      LLC/scIL-27 transfectants had reduced malignancy, including down-regulation of
      vimentin expression and reduction of cellular migration and invasion. The
      suppression of tumorigenesis by IL-27 on lung cancer cells was further confirmed
      by the treatment with rIL-27 on the murine LLC-1 and human non-small cell lung
      carcinoma (NSCLC) cell lines. PGE(2)-induced vimentin expression, movement, and
      invasiveness were also suppressed by the treatment with rIL-27. Our data show
      that IL-27 not only suppresses expression of COX-2 and PGE(2) but also decreases
      the levels of vimentin and the abilities of cellular migration and invasion.
      Furthermore, inoculation of LLC/scIL-27 into immunodeficient NOD/SCID mice also
      exhibited reduced tumor growth. Our data indicate that IL-27-induced nonimmune
      responses can contribute to significant antitumor effects. Taken together, the
      results suggest that IL-27 may serve as an effective agent for lung cancer
      therapy in the future.

PMID- 19841179
TI  - A NUP98-HOXD13 fusion gene impairs differentiation of B and T lymphocytes and
      leads to expansion of thymocytes with partial TCRB gene rearrangement.
AB  - Expression of a NUP98-HOXD13 (NHD13) fusion gene leads to myelodysplastic
      syndrome in mice. In addition to ineffective hematopoiesis, we observed that
      NHD13 mice were lymphopenic; the lymphopenia was due to a decrease in both T and
      B lymphocytes. Although the pro-B cell (B220(+)/CD43(+)) populations from the
      NHD13 and wild-type mice were similar, the NHD13 mice showed decreased pre-B
      cells (B220(+)/CD43(-)), indicating impaired differentiation at the pro-B to pre
      B stage. Thymi from NHD13 mice were smaller and overexpressed Hoxa cluster genes,
      including Hoxa7, Hoxa9, and Hoxa10. In addition, the NHD13 thymi contained fewer
      thymocytes, with an increased percentage of CD4(-)/CD8(-) (double-negative (DN))
      cells and a decreased percentage of CD4(+)/CD8(+) (double-positive) cells; the
      DN1/DN2 population was increased and the DN3/DN4 population was decreased,
      suggesting a partial block at the DN2 to DN3 transition. To determine clonality
      of the thymocytes, we used degenerate RT-PCR to identify clonal Tcrb gene
      rearrangements. Five of six NHD13 thymi showed an unusual Tcrb gene rearrangement
      pattern with common, clonal DJ rearrangements, but distinct V-D junctions,
      suggesting a marked clonal expansion of thymocytes that had undergone a DJ
      rearrangement, but not completed a VDJ rearrangement. Taken together, these
      findings demonstrate that expression of the NHD13 transgene inhibits lymphoid as
      well as myeloid and erythroid differentiation, results in overexpression of Hoxa
      cluster genes, and leads to a precursor T cell lymphoblastic leukemia/lymphoma.

PMID- 19841178
TI  - Regulatory T cell (Treg) subsets return in patients with refractory lupus
      following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are
      associated with immunological remission of lupus.
AB  - Compared with conventional drug therapy, autologous hemopoietic stem cell
      transplantation (HSCT) can induce very-long-term remission in refractory lupus
      patients. Herein, we show that in posttransplant patients, both
      CD4(+)CD25(high)FoxP3(+) and an unusual CD8(+)FoxP3(+) Treg subset return to
      levels seen in normal subjects; accompanied by almost complete inhibition of
      pathogenic T cell response to critical peptide autoepitopes from histones in
      nucleosomes, the major lupus autoantigen from apoptotic cells. In addition to a
      stably sustained elevation of FoxP3, posttransplant CD8 T cells also maintained
      markedly higher expression levels of latency-associated peptide (LAP), CD103, PD
      1, PD-L1, and CTLA-4, as compared with pretransplant CD8 T cells that were
      identically treated by a one-time activation and rest in short-term culture. The
      posttransplant CD8 regulatory T cells (Treg) have autoantigen-specific and
      nonspecific suppressive activity, which is contact independent and predominantly
      TGF-beta dependent. By contrast, the pretransplant CD8 T cells have helper
      activity, which is cell contact dependent. Although CD4(+)CD25(high) Treg cells
      return during clinical remission of conventional drug-treated lupus, the
      posttransplant patient's CD8 Treg cells are considerably more potent, and they
      are absent in drug-treated patients in whom CD4 T cell autoreactivity to
      nucleosomal epitopes persists even during clinical remission. Therefore, unlike
      conventional drug therapy, hemopoietic stem cell transplantation generates a
      newly differentiated population of LAP(high)CD103(high) CD8(TGF-beta) Treg cells,
      which repairs the Treg deficiency in human lupus to maintain patients in true
      immunological remission.

PMID- 19841181
TI  - Protein kinase B/Akt signals impair Th17 differentiation and support natural
      regulatory T cell function and induced regulatory T cell formation.
AB  - Protein kinase B (PKB)/Akt signals control T cell proliferation and
      differentiation but their effect on the generation and function of regulatory T
      cells (Treg) and Th17 cells is not well understood. In this study, we show that
      elevated PKB signals antagonize the immunosuppressive effect of TGF-beta1 on cell
      size, CD25 and CD98 expression, and proliferation of CD3-stimulated naive CD4(+)
      T cells from wild-type and CD28-deficient mice. Conventional CD4(+) T cells
      expressing active PKB are less susceptible to suppression by natural regulatory T
      cells. Although PKB signals do not affect the development of natural regulatory T
      cells, they enhance their suppressor capacity. Upon TCR triggering and TGF-beta1
      costimulation, wild-type and CD28-deficient CD4(+) T cells transgenic for PKB
      readily express Foxp3, thereby acquiring suppressor capacity. These effects of
      elevated PKB signals on T cell function involve a marked and sustained activation
      of STAT5 and Foxp3 and reduction in nuclear NFATc1 levels. In contrast, PKB
      signals impair TGF-beta1/IL-6-mediated differentiation of naive CD4(+) T cells
      into the Th17 lineage. This correlates with an increased signaling of ERK, STAT5,
      and STAT6. Finally, elevated PKB signals reduced the severity of experimental
      autoimmune encephalomyelitis in wild-type mice but induced experimental
      autoimmune encephalomyelitis in mice deficient for CD28. Altogether, these data
      indicate an important role of PKB signals on control of TGF-beta1-mediated T cell
      responses and, thereby, on tolerizing and inflammatory immune processes.

PMID- 19841180
TI  - Activation-induced CD154 expression abrogates tolerance induced by apoptotic
      cells.
AB  - The decision to generate a productive immune response or tolerance often depends
      on the context in which T cells first see Ag. Using a classical system of
      tolerance induction, we examined the immunological consequence of Ag encountered
      in the presence of naive or activated apoptotic cells. Naive apoptotic cells
      induced tolerance when injected i.v.; however, previously activated apoptotic
      cells induced immunity. Further analysis revealed a key role for CD154, as
      tolerance resulted after i.v. injection of either naive or activated apoptotic
      CD154(-/-) T cells, while coinjection of an agonistic anti-CD40 mAb with naive
      apoptotic T cells induced robust immunity. Dendritic cells fed activated
      apoptotic T cells in vitro produced IL-12p40 in a CD154-dependent manner, and the
      use of IL-12p40(-/-) mice or mAb-mediated neutralization of IL-12 revealed a link
      between CD154, IL-12, and the ability of activated apoptotic T cells to induce
      immunity rather than tolerance. Collectively, these results show that CD154
      expression on apoptotic T cells can determine the outcome of an immune response
      to Ag recognized within the context of the apoptotic cells and suggest that the
      balance between naive and activated apoptotic T cells may dictate whether a
      productive immune response is encouraged.

PMID- 19841182
TI  - Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and
      mediates an anti-inflammatory activity of chemerin in a lung disease model.
AB  - Chemerin is the ligand of the ChemR23 receptor and a chemoattractant factor for
      human immature dendritic cells (DCs), macrophages, and NK cells. In this study,
      we characterized the mouse chemerin/ChemR23 system in terms of pharmacology,
      structure-function, distribution, and in vivo biological properties. Mouse
      chemerin is synthesized as an inactive precursor (prochemerin) requiring, as in
      human, the precise processing of its C terminus for generating an agonist of
      ChemR23. Mouse ChemR23 is highly expressed in immature plasmacytoid DCs and at
      lower levels in myeloid DCs, macrophages, and NK cells. Mouse prochemerin is
      expressed in most epithelial cells acting as barriers for pathogens but not in
      leukocytes. Chemerin promotes calcium mobilization and chemotaxis on DCs and
      macrophages and these functional responses were abrogated in ChemR23 knockout
      mice. In a mouse model of acute lung inflammation induced by LPS, chemerin
      displayed potent anti-inflammatory properties, reducing neutrophil infiltration
      and inflammatory cytokine release in a ChemR23-dependent manner. ChemR23 knockout
      mice were unresponsive to chemerin and displayed an increased neutrophil
      infiltrate following LPS challenge. Altogether, the mouse chemerin/ChemR23 system
      is structurally and functionally conserved between human and mouse, and mouse can
      therefore be considered as a good model for studying the anti-inflammatory role
      of this system in the regulation of immune responses and inflammatory diseases.

PMID- 19841183
TI  - Role of gut commensal microflora in the development of experimental autoimmune
      encephalomyelitis.
AB  - Mucosal tolerance has been considered a potentially important pathway for the
      treatment of autoimmune disease, including human multiple sclerosis and
      experimental conditions such as experimental autoimmune encephalomyelitis (EAE).
      There is limited information on the capacity of commensal gut bacteria to induce
      and maintain peripheral immune tolerance. Inbred SJL and C57BL/6 mice were
      treated orally with a broad spectrum of antibiotics to reduce gut microflora.
      Reduction of gut commensal bacteria impaired the development of EAE.
      Intraperitoneal antibiotic-treated mice showed no significant decline in the gut
      microflora and developed EAE similar to untreated mice, suggesting that reduction
      in disease activity was related to alterations in the gut bacterial population.
      Protection was associated with a reduction of proinflammatory cytokines and
      increases in IL-10 and IL-13. Adoptive transfer of low numbers of IL-10-producing
      CD25(+)CD4(+) T cells (>75% FoxP3(+)) purified from cervical lymph nodes of
      commensal bacteria reduced mice and in vivo neutralization of CD25(+) cells
      suggested the role of regulatory T cells maintaining peripheral immune
      homeostasis. Our data demonstrate that antibiotic modification of gut commensal
      bacteria can modulate peripheral immune tolerance that can protect against EAE.
      This approach may offer a new therapeutic paradigm in the treatment of multiple
      sclerosis and perhaps other autoimmune conditions.

PMID- 19841184
TI  - Reduced diabetes in btk-deficient nonobese diabetic mice and restoration of
      diabetes with provision of an anti-insulin IgH chain transgene.
AB  - Type 1 diabetes results from T cell-mediated destruction of insulin-producing
      beta cells. Although elimination of B lymphocytes has proven successful at
      preventing disease, modulation of B cell function as a means to prevent type 1
      diabetes has not been investigated. The development, fate, and function of B
      lymphocytes depend upon BCR signaling, which is mediated in part by Bruton's
      tyrosine kinase (BTK). When introduced into NOD mice, btk deficiency only
      modestly reduces B cell numbers, but dramatically protects against diabetes. In
      NOD, btk deficiency mirrors changes in B cell subsets seen in other strains, but
      also improves B cell-related tolerance, as indicated by failure to generate
      insulin autoantibodies. Introduction of an anti-insulin BCR H chain transgene
      restores diabetes in btk-deficient NOD mice, indicating that btk-deficient B
      cells are functionally capable of promoting autoimmune diabetes if they have a
      critical autoimmune specificity. This suggests that the disease-protective effect
      of btk deficiency may reflect a lack of autoreactive specificities in the B cell
      repertoire. Thus, signaling via BTK can be modulated to improve B cell tolerance,
      and prevent T cell-mediated autoimmune diabetes.

PMID- 19841185
TI  - Critical role of TLR2 and TLR4 in autoantibody production and glomerulonephritis
      in lpr mutation-induced mouse lupus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      pathogenic autoantibodies directed against nuclear Ags and immune complex
      deposits in damaged organs. Environmental factors have been thought to play a
      role in the onset of the disease. The recognition of these factors is mediated by
      TLRs, in particular TLR2 and TLR4 which bind pathogen-associated molecular
      patterns of Gram(+) and Gram(-) bacteria, respectively. We attempted to determine
      the role of these TLRs in SLE by creating TLR2- or TLR4-deficient
      C57BL/6(lpr/lpr) mice. These mice developed a less severe disease and fewer
      immunological alterations. Indeed, in C57BL/6(lpr/lpr)-TLR2 or -TLR4-deficient
      mice, glomerular IgG deposits and mesangial cell proliferation were dramatically
      decreased and antinuclear, anti-dsDNA, and anti-cardiolipin autoantibody titers
      were significantly reduced. However, the response against nucleosome remained
      unaffected, indicating a role of TLR2 and TLR4 in the production of Abs directed
      against only certain categories of SLE-related autoantigens. Analysis of B cell
      phenotype showed a significant reduction of marginal zone B cells, particularly
      in C57BL/6(lpr/lpr)-TLR4-deficient mice, suggesting an important role of TLR4 in
      the sustained activation of these cells likely involved in autoantibody
      production. Interestingly, the lack of TLR4 also affected the production of
      cytokines involved in the development of lupus disease.

PMID- 19841187
TI  - Human late memory CD8+ T cells have a distinct cytokine signature characterized
      by CC chemokine production without IL-2 production.
AB  - Late memory T cell skewing is observed in the setting of immune recovery after
      cord blood transplantation, and may be associated with inferior control of viral
      reactivation and cancers. Therefore, we sought to understand how late memory
      cells differ functionally from earlier stage memory T cells, and whether surface
      phenotypes associated with differentiation stages were predictably associated
      with functional signatures. Higher order cytokine flow cytometry allows
      characterization of human T cells based on complex phenotypic markers and their
      differential capacity to simultaneously secrete effector proteins, including
      cytokines and chemokines. We used 8-color, 10-parameter cytokine flow cytometry
      to characterize the functional activation of human late memory CD8(+) T cells
      defined by CD45RA and CD27 expression (CD27(-)CD45RA(+)). We assessed the 15
      possible functional signatures of cells defined by production of IL-2, IFN-gamma,
      TNF-alpha, and MIP-1beta alone or in combination, following activation with Ags
      stimulating bypassing surface proteins (PMA:ionomycin) or through the TCR (e.g.,
      viral Ags). Late memory CD8(+) T cells produced abundant amounts of CC chemokines
      (MIP-1beta, MIP-1alpha, and RANTES) but not IL-2. IL-2/IFN-gamma coproduction,
      characteristic of protective immune responses to viral infections, was absent in
      late memory CD8(+) T cells. These data demonstrate that functional cytokine
      signatures are predictably associated with CD8(+) maturation stages, and that the
      polarization of late memory CD8(+) T cells toward CC chemokine production and
      away from IL-2 production suggests a unique functional role for this subset.

PMID- 19841188
TI  - Mouse mast cell protease 4 is the major chymase in murine airways and has a
      protective role in allergic airway inflammation.
AB  - It is widely established that mast cells (MCs) have a harmful role in asthma, for
      example by secreting various proinflammatory substances stored within their
      secretory granule. However, in this study, we show that one of the substances
      stored within MC granule, chymase, in fact has a protective role in allergic
      airway inflammation, indicating that MCs may possess both harmful and protective
      activities in connection with this type of disease. Wild-type (WT) mice and mice
      lacking mouse MC protease 4 (mMCP-4), a chymase that is functionally homologous
      to human chymase, were sensitized and challenged with OVA, followed by the
      assessment of airway physiology and inflammatory parameters. Our results show
      that the airway hyperresponsiveness was significantly higher in mMCP-4(-/-) as
      compared with WT mice. Moreover, the degree of lung tissue inflammation was
      markedly higher in mice lacking mMCP-4 than in WT controls. Histological analysis
      revealed that OVA sensitization/challenge resulted in a marked increased in the
      thickness of the smooth muscle cell (SMC) layer and, notably, that the degree of
      SMC layer thickening was more pronounced in mMCP-4(-/-) animals than in WT
      controls, thus indicating that chymase may have an effect on airway SMCs. In
      support of this, mMCP-4-positive MCs were located in the close vicinity of the
      SMC layer, mainly in the upper airways, and mMCP-4 was shown to be the major
      chymase expressed in these MCs. Taken together, our results indicate that chymase
      present in the upper airways protects against allergic airway responses, possibly
      by regulating SMCs.

PMID- 19841186
TI  - Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappaB
      paradigm.
AB  - Mucin over-production is one of the hallmarks of chronic airway diseases such as
      chronic obstructive pulmonary disease, asthma, and cystic fibrosis. NF-kappaB
      activation in airway epithelial cells has been shown to play a positive
      inflammatory role in chronic airway diseases; however, the role of NF-kappaB in
      mucin gene expression is unresolved. In this study, we have shown that the
      proinflammatory cytokines, IL-1beta and IL-17A, both of which utilize the NF
      kappaB pathway, are potent inducers of mucin (MUC)5AC mRNA and protein synthesis
      by both well-differentiated primary normal human bronchial epithelial cells and
      the human bronchial epithelial cell line, HBE1. MUC5AC induction by these
      cytokines was both time- and dose-dependent and occurred at the level of promoter
      activation, as measured by a reporter gene assay. These effects were attenuated
      by the small molecule inhibitor NF-kappaB inhibitor III, as well as p65 small
      interfering RNA, suggesting that the regulation of MUC5AC expression by these
      cytokines is via an NF-kappaB-based transcriptional mechanism. Further
      investigation of the promoter region identified a putative NF-kappaB binding site
      at position-3594/-3582 in the promoter of MUC5AC as critical for the regulation
      of MUC5AC expression by both IL-1beta and IL-17A. Chromatin immunoprecipitation
      analysis confirmed enhanced binding of the NF-kappaB subunit p50 to this region
      following cytokine stimulation. We conclude that an NF-kappaB-based
      transcriptional mechanism is involved in MUC5AC regulation by IL-1beta and IL-17A
      in the airway epithelium. This is the first demonstration of the participation of
      NF-kappaB and its specific binding site in cytokine-mediated airway MUC5AC
      expression.

PMID- 19841189
TI  - Localization of Kv1.3 channels in the immunological synapse modulates the calcium
      response to antigen stimulation in T lymphocytes.
AB  - The immunological synapse (IS), a highly organized structure that forms at the
      point of contact between a T cell and an APC, is essential for the proper
      development of signaling events, including the Ca(2+) response. Kv1.3 channels
      control Ca(2+) homeostasis in human T cells and move into the IS upon Ag
      presentation. However, the process involved in channel accumulation in the IS and
      the functional implications of this localization are not yet known. Here we
      define the movement of Kv1.3 into the IS and study whether Kv1.3 localization
      into the IS influences Ca(2+) signaling in Jurkat T cells. Crosslinking of the
      channel protein with an extracellular Ab limits Kv1.3 mobility and accumulation
      at the IS. Moreover, Kv1.3 recruitment to the IS does not involve the transport
      of newly synthesized channels and it does not occur through recycling of membrane
      channels. Kv1.3 localization in the IS modulates the Ca(2+) response. Blockade of
      Kv1.3 movement into the IS by crosslinking significantly increases the amplitude
      of the Ca(2+) response triggered by anti-CD3/anti-CD28-coated beads, which induce
      the formation of the IS. On the contrary, the Ca(2+) response induced by TCR
      stimulation without the formation of the IS with soluble anti-CD3/anti-CD28 Abs
      is unaltered. The results presented herein indicate that, upon Ag presentation,
      membrane-incorporated Kv1.3 channels move along the plasma membrane to localize
      in the IS. This localization is important to control the amplitude of the Ca(2+)
      response, and disruption of this process can account for alterations of
      downstream Ca(2+)-dependent signaling events.

PMID- 19841190
TI  - The proteasome inhibitor bortezomib enhances the susceptibility to viral
      infection.
AB  - The proteasome, a multicatalytic protease, is responsible for the generation of
      most MHC class I ligands. Bortezomib, a proteasome inhibitor, is clinically
      approved for treatment of multiple myeloma and mantle cell myeloma. In the
      present study, we investigated the effect of bortezomib on viral infection.
      Infection of bortezomib-treated mice with the lymphocytic choriomeningitis virus
      (LCMV) led to a decreased cytotoxic T cell response to several LCMV-derived
      CD8(+) T cell epitopes. Bortezomib treatment caused a reduced expansion of CD8(+)
      T lymphocytes and increased viral titers in LCMV-infected mice. Administration of
      bortezomib during expansion of CD8(+) T cells had no influence on the cytotoxic T
      cell response, suggesting that bortezomib interferes with priming of naive T
      cells. Indeed, determination of Ag load in spleen 4 days post infection, revealed
      a reduced presentation of LCMV-derived cytotoxic T cell epitopes on MHC class I
      molecules. In summary, we show that proteasome inhibition with bortezomib led to
      an increased susceptibility to viral infection, and demonstrate for the first
      time, that proteasome inhibitors can alter Ag processing in vivo.

PMID- 19841193
TI  - Invited review: milk protein polymorphisms in cattle: effect on animal breeding
      and human nutrition.
AB  - The 6 main milk proteins in cattle are encoded by highly polymorphic genes
      characterized by several nonsynonymous and synonymous mutations, with up to 47
      protein variants identified. Such an extensive variation was used for linkage
      analysis with the description of the casein cluster more than 30 yr ago and has
      been applied to animal breeding for several years. Casein haplotype effects on
      productive traits have been investigated considering information on the whole
      casein complex. Moreover, mutations within the noncoding sequences have been
      shown to affect the specific protein expression and, as a consequence, milk
      composition and cheesemaking. Milk protein variants are also a useful tool for
      breed characterization, diversity, and phylogenetic studies. In addition, they
      are involved in various aspects of human nutrition. First, the occurrence of
      alleles associated with a reduced content of different caseins might be exploited
      for the production of milk with particular nutritional qualities; that is,
      hypoallergenic milk. On the other hand, the frequency of these alleles can be
      decreased by selection of sires using simple DNA tests, thereby increasing the
      casein content in milk used for cheesemaking. Furthermore, the biological
      activity of peptides released from milk protein digestion can be affected by
      amino acid exchanges or deletions resulting from gene mutations. Finally, the
      gene-culture coevolution between cattle milk protein genes and human lactase
      genes, which has been recently highlighted, is impressive proof of the nonrandom
      occurrence of milk protein genetic variation over the centuries.

PMID- 19841191
TI  - CCR7-dependent stimulation of survival in dendritic cells involves inhibition of
      GSK3beta.
AB  - Chemokine receptor CCR7 regulates chemotaxis and survival in mature dendritic
      cells (DCs). We studied the role of glycogen synthase kinase-3beta (GSK3beta) in
      the regulation of CCR7-dependent survival. We show that GSK3beta behaves as a
      proapoptotic regulator in cultured monocyte-derived human DCs and murine splenic
      DCs in vitro, and in lymph node DCs in vivo. In keeping with its prosurvival
      role, stimulation of CCR7 induced phosphorylation/inhibition of GSK3beta, which
      was mediated by the prosurvival regulator Akt1, but it was independent of ERK1/2,
      a key regulator of chemotaxis. Stimulation of CCR7 also induced translocation of
      two transcription-factor targets of Akt, prosurvival NF-kappaB and proapoptotic
      FOXO1, to the nucleus and cytosol, respectively, resulting in DCs with a
      phenotype more resistant to apoptotic stimuli. We analyzed if GSK3beta was able
      to modulate the mobilizations of these transcription factors. Using
      pharmacological inhibitors, small interfering RNA, and a construct encoding
      constitutively active GSK3beta, we show that active GSK3beta fosters and hampers
      the translocations to the nucleus of FOXO and NF-kappaB, respectively. Inhibition
      of GSK3beta resulted in the degradation of the NF-kappaB inhibitor IkappaB,
      indicating a mechanism whereby GSK3 can control the translocation of NF-kappaB to
      the nucleus. GSK3beta and FOXO interacted in vivo, suggesting that this
      transcription factor could be a substrate of GSK3. The results provide a novel
      mechanism whereby active GSK3beta contributes to regulate apoptosis in DCs. They
      also suggest that upon stimulation of CCR7, Akt-mediated
      phosphorylation/inhibition of GSK3beta may be required to allow complete
      translocations of FOXO and NF-kappaB that confer DCs an extended survival.

PMID- 19841194
TI  - Hot topic: sonication increases the heat stability of whey proteins.
AB  - The thickening or gelling of protein-based dairy streams and ingredients upon
      exposure to heat has been an ongoing problem in dairy processing for many
      decades. This phenomenon can restrict the range of dairy product options and
      reduce manufacturing efficiencies by limiting the type and extent of heat
      treatment that can be used. In this report, we outline a novel approach to
      overcoming this problem. The use of preheating treatments to induce whey protein
      aggregate formation in whey products is well known in the field. However, we show
      that the application of ultrasound for a very short duration after such a heating
      step breaks down these aggregates and prevents their reformation on subsequent
      heating, thereby reducing the viscosity increase that is usually associated with
      this process. This novel technique has the potential to provide significant
      economic benefit to the dairy manufacturing industry.

PMID- 19841192
TI  - CD69 gene is differentially regulated in T and B cells by evolutionarily
      conserved promoter-distal elements.
AB  - CD69 is a type II C-type lectin involved in lymphocyte migration and cytokine
      secretion. CD69 expression represents one of the earliest available indicators of
      leukocyte activation and its rapid induction occurs through transcriptional
      activation. In this study we examined the molecular mechanism underlying mouse
      CD69 gene transcription in vivo in T and B cells. Analysis of the 45-kb region
      upstream of the CD69 gene revealed evolutionary conservation at the promoter and
      at four noncoding sequences (CNS) that were called CNS1, CNS2, CNS3, and CNS4.
      These regions were found to be hypersensitive sites in DNase I digestion
      experiments, and chromatin immunoprecipitation assays showed specific epigenetic
      modifications. CNS2 and CNS4 displayed constitutive and inducible enhancer
      activity in transient transfection assays in T cells. Using a transgenic approach
      to test CNS function, we found that the CD69 promoter conferred developmentally
      regulated expression during positive selection of thymocytes but could not
      support regulated expression in mature lymphocytes. Inclusion of CNS1 and CNS2
      caused suppression of CD69 expression, whereas further addition of CNS3 and CNS4
      supported developmental-stage and lineage-specific regulation in T cells but not
      in B cells. We concluded CNS1-4 are important cis-regulatory elements that
      interact both positively and negatively with the CD69 promoter and that
      differentially contribute to CD69 expression in T and B cells.

PMID- 19841195
TI  - Isolation of caseins from whey proteins by microfiltration modifying the mineral
      balance in skim milk.
AB  - The objective of this work was to study the effect of different salts and salt
      concentration on the isolation of casein micelles from bovine raw skim milk by
      tangential flow microfiltration. Tangential flow microfiltration (0.22 microm)
      was conducted in a continuous process adding a modified buffer to maintain a
      constant initial sample volume. This buffer contained calcium chloride (CaCl2),
      sodium phosphate (Na2HPO4), or potassium citrate (K3C6H5O7) in concentrations
      ranging from 0 to 100 mM. The concentrations of caseins and whey proteins
      retained were determined by sodium dodecyl sulfate-PAGE and analyzed using the
      Scion Image software (Scion Corporation, Frederick, MD). A complete isolation of
      caseins from whey proteins was achieved using sodium phosphate in the range of 10
      to 50 mM and 20 times the initial volume of buffer added. No whey proteins were
      detected at 50 mM but this was at the expense of low caseins being retained. When
      lower sodium phosphate concentrations were used, the amount of caseins retained
      was higher but a small amount of whey proteins were still detected by sodium
      dodecyl sulfate-PAGE. Among the salts tested, calcium chloride at 50 mM and all
      volumes of buffer showed the higher retention of casein proteins. The highest
      casein:whey protein ratio was found at 30 mM CaCl2, but no complete casein
      micelle isolation was achieved. Potassium citrate was the most ineffective salt
      because a rapid loss of caseins and whey proteins was observed at all
      concentrations and with low quantities of buffer added during the filtration
      process. Our results show the potential of altering the mineral balance in milk
      for isolation of casein micelles from whey proteins in a continuous tangential
      flow microfiltration system.

PMID- 19841196
TI  - Variations in the transfer of radiocesium (137Cs) and radiostrontium (90Sr) from
      milk to cheese.
AB  - This study aimed to compare the transfer of 2 manmade radionuclides, radiocesium
      (137Cs) and radiostrontium (90Sr), from cow milk to whey and cheese in 3
      different types of French cheese production with rennet coagulation. Most of the
      137Cs was present in the aqueous phase and became concentrated in the whey. For
      137Cs transfer to whey, the processing factor (Pf; i.e., the ratio of the
      activity concentrations) ranged between 0.86 and 1.30 (n = 12). The food
      processing retention factor (Fr), calculated using the processing efficiency,
      ranged between 0.85 and 1.19 (n = 9). No statistical difference of Pf and Fr to
      whey is identified for 137Cs and the cheese products. The Pf calculated for 90Sr
      transfer to cheese ranged between 3.95 and 12.16, with significant differences
      depending on the type of cheese. In addition, a linear correlation is observed
      between 90Sr Pf to cheese and the Ca level in the cheese (r2 = 0.57). Thus, the
      Pf is enhanced in hard cheeses that are enriched in calcium. This is confirmed by
      nearly constant Fr values, ranging between 0.66 and 0.83.

PMID- 19841197
TI  - Physicochemical characterization of mozzarella cheese wheys and stretchwaters in
      comparison with several other sweet wheys.
AB  - To better understand the origins of the problems occurring during mozzarella
      cheese whey concentration, lactose crystallization, and spray-drying steps, a
      physicochemical characterization was achieved. For this purpose, mozzarella
      cheese wheys were sampled and their content in different compounds such as total
      nitrogen, noncasein nitrogen, nonprotein nitrogen, lactate, citrate, chloride,
      sulfate, phosphate anions, calcium, magnesium, potassium, sodium cations, and the
      sugars glucose and galactose were measured. In a second step, the results were
      compared with the corresponding content in cheddar cheese wheys, raclette cheese
      wheys, soft cheese wheys, and Swiss-type cheese wheys. At the end of this survey,
      it was shown that mozzarella cheese wheys were more concentrated in lactate and
      in minerals--especially phosphate, calcium, and magnesium--than the other cheese
      wheys and that they contained galactose. These constituents are known to be
      hygroscopic. Complementary surveys are now necessary to compare the
      hygroscopicity of galactose and lactate and discover whether the amounts of these
      compounds found in mozzarella cheese wheys are a factor in the problems
      encountered during the concentration, lactose crystallization, and spray-drying
      steps.

PMID- 19841198
TI  - Considerable variation in the concentration of osteopontin in human milk, bovine
      milk, and infant formulas.
AB  - Osteopontin (OPN) is a multifunctional bioactive protein that is implicated in
      numerous biological processes such as bone remodeling, inhibition of ectopic
      calcification, and cellular adhesion and migration, as well as several immune
      functions. Osteopontin has cytokine-like properties and is a key factor in the
      initiation of T helper 1 immune responses. Osteopontin is present in most tissues
      and body fluids, with the highest concentrations being found in milk. In the
      present study, ELISA for human and bovine milk OPN were developed and OPN
      concentration in human breast milk, bovine milk, and infant formulas was measured
      and compared. The OPN concentration in human milk was measured to approximately
      138 mg/L, which corresponds to 2.1% (wt/wt) of the total protein in human breast
      milk. This is considerably higher than the corresponding OPN concentrations in
      bovine milk (approximately 18 mg/L) and infant formulas (approximately 9 mg/L).
      Moreover, bovine milk OPN is shown to induce the expression of the T helper 1
      cytokine IL-12 in cultured human lamina propria mononuclear cells isolated from
      intestinal biopsies. Finally, the OPN concentration in plasma samples from
      umbilical cords, 3-mo-old infants, and pregnant and nonpregnant adults was
      measured. The OPN level in plasma from 3-mo-old infants and umbilical cords was
      found to be 7 to 10 times higher than in adults. Thus, the high levels of OPN in
      milk and infant plasma suggest that OPN is important to infants and that ingested
      milk OPN is likely to induce cytokine production in neonate intestinal immune
      cells.

PMID- 19841199
TI  - Validation of a curd-syneresis sensor over a range of milk composition and
      process parameters.
AB  - An online visible-near-infrared sensor was used to monitor the course of
      syneresis during cheesemaking with the purpose of validating syneresis indices
      obtained using partial least squares, with cross-validation across a range of
      milk fat levels, gel firmness levels at cutting, curd cutting programs, stirring
      speeds, milk protein levels, and fat:protein ratio levels. Three series of trials
      were carried out in an 11-L cheese vat using recombined whole milk. Three
      factorial experimental designs were used, consisting of 1) 3 curd stirring speeds
      and 3 cutting programs; 2) 3 milk fat levels and 3 gel firmness levels at
      cutting; and 3) 2 milk protein levels and 3 fat:protein ratio levels,
      respectively. Milk was clotted under constant conditions in all experiments and
      the gel was cut according to the respective experimental design. Prediction
      models for production of whey and whey fat losses were developed in 2 of the
      experiments and validated in the other experiment. The best models gave standard
      error of prediction values of 6.6 g/100 g for yield of whey and 0.05 g/100 g for
      fat in whey, as compared with 4.4 and 0.013 g/100 g, respectively, for the
      calibration data sets. Robust models developed for predicting yield of whey and
      whey fat losses using a validation method have potential application in the
      cheese industry.

PMID- 19841200
TI  - Fat content increases the lethality of ultra-high-pressure homogenization on
      Listeria monocytogenes in milk.
AB  - Listeria monocytogenes CCUG 15526 was inoculated at a concentration of
      approximately 7.0 log(10) cfu/mL in milk samples with 0.3, 3.6, 10, and 15% fat
      contents. Milk samples with 0.3 and 3.6% fat content were also inoculated with a
      lower load of approximately 3.0 log(10) cfu/mL. Inoculated milk samples were
      subjected to a single cycle of ultra-high-pressure homogenization (UHPH)
      treatment at 200, 300, and 400 MPa. Microbiological analyses were performed 2 h
      after the UHPH treatments and after 5, 8, and 15 d of storage at 4 degrees C.
      Maximum lethality values were observed in samples treated at 400 MPa with 15 and
      10% fat (7.95 and 7.46 log(10) cfu/mL), respectively. However, in skimmed and
      3.6% fat milk samples, complete inactivation was not achieved and, during the
      subsequent 15 d of storage at 4 degrees C, L. monocytogenes was able to recover
      and replicate until achieving initial counts. In milk samples with 10 and 15%
      fat, L. monocytogenes recovered to the level of initial counts only in the milk
      samples treated at 200 MPa but not in the milk samples treated at 300 and 400
      MPa. When the load of L. monocytogenes was approximately 3.0 log(10) cfu/mL in
      milk samples with 0.3 and 3.6% fat, complete inactivation was not achieved and L.
      monocytogenes was able to recover and grow during the subsequent cold storage.
      Fat content increased the maximum temperature reached during UHPH treatment; this
      could have contributed to the lethal effect achieved, but the amount of fat of
      the milk had a stronger effect than the temperature on obtaining a higher death
      rate of L. monocytogenes.

PMID- 19841201
TI  - Quality characteristics and consumer acceptance of yogurt fortified with date
      fiber.
AB  - Yogurt is considered a healthy food and incorporating dietary fiber will make it
      even healthier. Date fiber (DF), a by-product of date syrup production, is a good
      source of dietary fiber. The effect of fortification with DF on fresh yogurt
      quality was investigated. Acidity, pH, color [L* (lightness), a* (redness), and
      b* (yellowness) values], texture profile, sensory properties, and consumer
      acceptance were studied. Control yogurt (without fiber), yogurt fortified with
      1.5, 3.0, and 4.5% DF, and yogurt with 1.5% wheat bran (WB) were prepared.
      Fortification with DF did not cause significant changes in yogurt acidity,
      although pH was increased. Yogurts fortified with DF had firmer texture (higher
      hardness values) and darker color (lower L* and higher a*) compared with control
      or WB yogurts. Consumer test results indicated that the appearance, color, and
      flavor ratings were significantly affected by fiber fortification. Yogurt
      fortified with up to 3% DF had similar sourness, sweetness, firmness, smoothness,
      and overall acceptance ratings as the control yogurt. Sensory ratings and
      acceptability of yogurt decreased significantly when increasing DF to 4.5% or
      using 1.5% WB. Flavoring yogurt fortified with 4.5% DF with vanilla did not
      improve flavor or overall acceptance ratings. Thus, fortifying yogurt with 3% DF
      produced acceptable yogurt with beneficial health effects.

PMID- 19841202
TI  - Short communication: detection of Mycobacterium avium subspecies paratuberculosis
      by polymerase chain reaction in bovine milk in Brazil.
AB  - Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of
      paratuberculosis, or Johne's disease, a chronic granulomatous enteritis that
      affects all ruminants worldwide. Since the isolation of MAP from intestinal
      tissue of human patients bearing Crohn's disease, there has been a debate on the
      possibility of this agent playing a role in the etiology of Crohn's disease. Milk
      could be the potential vehicle for transmission to humans. Mycobacterium avium
      ssp. paratuberculosis has already been detected in milk samples worldwide. In
      Brazil, detection of MAP is uncommon; however, it has already been detected by
      bacterial isolation and serological test. The aim of this study was to
      investigate the presence of MAP, by PCR, in raw milk samples in the region of
      Vicosa, Minas Gerais State, Brazil. Of 222 milk samples evaluated, 8 (3.6%)
      quarter milk samples amplified fragments of similar size to that expected of 626
      bp. These fragments were cloned and sequenced. The genetic analysis revealed a
      99% identity match between the sequences obtained in this study and the insertion
      sequence IS900 deposited in the GenBank. In the analyzed milk samples, MAP DNA
      was detected, confirming its presence in dairy cattle in the region of Vicosa.
      This is the first report of MAP presence in raw milk samples in Brazil.

PMID- 19841203
TI  - Chromium supplementation and substitution of barley grain with corn: Effects on
      performance and lactation in periparturient dairy cows.
AB  - Thirty-two multiparous Holstein cows were used to investigate the effects of
      chromium-l-methionine (Cr-Met) supplementation and dietary grain source on
      performance and lactation during the periparturient period. Cows were fed a total
      mixed ration consisting of either a barley-based diet (BBD) or a corn-based diet
      (CBD) from 21 d before anticipated calving through 28 d after calving. The Cr-Met
      was supplemented at dosages of 0 or 0.08 mg of Cr/kg of metabolic body weight.
      The study was designed as a randomized complete block design with 2 (Cr-Met
      levels) x 2 (grain sources) factorial arrangement. There was no Cr effect on
      prepartum dry matter intake (DMI) or postpartum DMI, body weight (BW), net energy
      balance, and whole tract apparent digestibility of nutrients. Prepartum DMI as a
      percentage of BW tended to increase with Cr-Met. Supplemental Cr-Met tended to
      increase milk yield whereas milk protein percentage decreased. Pre- and
      postpartum DMI, BW, net energy balance, milk yield, and milk composition were not
      affected by substituting ground barley with ground corn. The addition of Cr-Met
      increased prepartum DMI and tended to increase postpartum DMI of the BBD but not
      the CBD. The change in prepartum DMI was smaller when the BBD was supplemented
      with Cr-Met but remained unchanged when the CBD was supplemented with Cr-Met.
      Yields of crude protein and total solids in milk and prepartum digestibility of
      DM and organic matter tended to increase when Cr-Met was added to the BBD but
      remained unchanged when added to the CBD. Periparturient cows failed to respond
      to the grain source of the diet, whereas they showed greater response in milk
      yield to diets supplemented with Cr-Met. In conclusion, the present results
      demonstrate that the beneficial effect of Cr-Met supplementation during the
      periparturient period to improve feed intake may depend on the grain source of
      the diet.

PMID- 19841204
TI  - Identification of potential markers in blood for the development of subclinical
      and clinical mastitis in dairy cattle at parturition and during early lactation.
AB  - Our objective was to identify specific blood markers as risk factors for the
      development of mastitis during early lactation. We used a subset of cows from a
      larger experiment that consisted of a total of 634 lactations from 317 cows. Cows
      were of 3 breeds and ranged from parity 1 to 4. Blood samples were collected
      weekly from 56 d before expected calving date through 90 d in milk (DIM). Blood
      was analyzed for several hormones, metabolites, and enzymes, and energy intake
      and energy balance were calculated. Veterinary treatment records and daily
      composite milk somatic cell counts were analyzed and used to determine incidence
      and severity of mastitis in early lactation. Cows were separated into 2 groups:
      1) WK0, consisting of cows that developed clinical mastitis (CM), cows that
      developed subclinical mastitis (SM), or cows that were healthy (H) during the
      first 7 DIM; and 2) EL, consisting of CM, SM, or H cows during wk 2 through 13 of
      lactation. Data were adjusted for numerous fixed effects (e.g., parity, breed,
      season, and DIM) before statistical analysis. The time of mastitis (TOM) was
      recorded as the DIM in which the first rise in somatic cell count was observed
      and was recorded as TOM = 0. The time before and after TOM was distinguished as
      +/- n wk relative to TOM = 0. Healthy cows were paired with either a SM or CM cow
      and the TOM for each H cow was equal to the TOM for its paired SM or CM cow. Data
      from wk -1 and -2 relative to TOM were analyzed for group WK0 and EL,
      respectively. For all parameters, SM cows did not differ from H cows from either
      group. The CM cows had higher nonesterified fatty acid levels and a tendency
      toward higher beta-hydroxybutyrate levels than H cows before mastitis for both
      groups. For group WK0, glucose was higher -1 wk relative to calving in CM than H
      cows. For group EL, aspartate aminotransferase was higher -2 wk relative to
      mastitis in CM than H cows during 8 to 90 DIM. All other variables were similar
      among CM, SM, and H cows for both groups. Our results indicate that substances in
      blood, especially nonesterified fatty acids and aspartate aminotransferase, may
      be potential markers for the risk of mastitis in early lactation.

PMID- 19841205
TI  - Evaluation of the Metricheck device and the gloved hand for the diagnosis of
      clinical endometritis in dairy cows.
AB  - The objective of this study was to compare 2 surrogate vaginal examination
      methods (i.e., gloved hand and a vaginal device) with vaginoscopy as a reference
      method for diagnosing clinical endometritis in dairy cows. Holstein-Friesian cows
      (n = 1,002) in 2 commercial dairy herds in Germany were examined for endometritis
      at 21 to 27 d in milk (DIM) by using 1 of 3 vaginal diagnostic methods. Vaginal
      examinations were performed either with a speculum (reference method), a vaginal
      device (Metricheck, Simcro, New Zealand), or a gloved hand. Vaginal discharge
      adhering to the diagnostic tool was classified according to a vaginal discharge
      score ranging from 0 to 3 (where 0 = translucent mucus, 1 = mucus containing
      flecks of white or off-white pus, 2 = less than 50% white or off-white
      mucopurulent material, and 3 = greater than 50% white or yellow pus that may be
      sanguineous). Cows with vaginal discharge scores of 1 to 3 received 500 microg of
      cloprostenol after examination and again 14 d later (35 to 41 DIM). The
      prevalence of endometritis in both herds was 40.6 and 40.3%, respectively. With
      the Metricheck device, significantly more cows were diagnosed as affected with
      endometritis than by examination with a speculum or a gloved hand (47.5 vs. 36.9
      and 36.8%). Binary logistic regression for the risk of conception after first AI
      as an outcome variable, with vaginal discharge score, diagnostic method, and farm
      as covariates, revealed a significant effect of degree of endometritis, but not
      of the diagnostic methods. Survival analyses for the hazard of insemination and
      pregnancy within 200 DIM, respectively, revealed a significant effect of degree
      of endometritis, herd, and parity, but not of the diagnostic tool. It can be
      concluded that any one of the 3 vaginal examination methods can be used
      interchangeably, without a negative effect on reproductive performance.

PMID- 19841206
TI  - Effect of increasing amounts of supplemental progesterone in a timed artificial
      insemination protocol on fertility of lactating dairy cows.
AB  - The objectives were to evaluate the effect of supplemental progesterone during a
      timed artificial insemination (TAI) protocol on pregnancy per insemination and
      pregnancy loss. Lactating dairy cows from 2 dairy herds were presynchronized with
      2 injections of PGF(2alpha) 14 d apart, and cows observed in estrus following the
      second PGF(2alpha) injection were inseminated (n = 1,301). Cows not inseminated
      by 11 d after the end of the presynchronization were submitted to the TAI
      protocol (d 0 GnRH, d 7 PGF(2alpha), d 8 estradiol cypionate, and d 10 TAI). On
      the day of the GnRH of the TAI protocol (study d 0), cows were assigned randomly
      to receive no exogenous progesterone (control = 432), one controlled internal
      drug-release (CIDR) insert (CIDR1 = 440), or 2 CIDR inserts (CIDR2 = 440)
      containing 1.38 g of progesterone each from study d 0 to 7. Blood was sampled on
      study d 0 before insertion of CIDR for determination of progesterone
      concentration in plasma, and cows with concentration <1.0 ng/mL were classified
      as low progesterone (LP) and those with concentration > or =1.0 ng/mL were
      classified as high progesterone (HP). From a subgroup of 240 cows, blood was
      sampled on study d 3, 7, 17 and 24 and ovaries were examined by ultrasonography
      on study d 0 and 7. Pregnancy was diagnosed at 38 +/- 3 and 66 +/- 3 d after AI.
      Data were analyzed including only cows randomly assigned to treatments and
      excluding cows that were inseminated after the second PGF(2alpha) injection. The
      proportion of cows classified as HP at the beginning of the TAI protocol was
      similar among treatments, but differed between herds. Concentrations of
      progesterone in plasma during the TAI protocol increased linearly with number of
      CIDR used, and the increment was 0.9 ng/mL per CIDR. The proportion of cows with
      plasma progesterone > or =1.0 ng/mL on study d 17 was not affected by treatment,
      but a greater proportion of control than CIDR-treated cows had asynchronous
      estrous cycles following the TAI protocol. Treatment with CIDR inserts, however,
      did not affect pregnancy at 38 +/- 3 and 66 +/- 3 d after AI or pregnancy loss.

PMID- 19841207
TI  - Once-daily milking effects in high-yielding Alpine dairy goats.
AB  - Two experiments were conducted to determine the milk loss of high-yielding Alpine
      goats resulting from once-daily milking (ODM) and its relationship to udder
      cisternal size. We investigated the effects of application of this management
      strategy on milk yield, composition, and technological parameters: lipolysis, fat
      globule size, and cheese yield. In a second experiment, we investigated the
      effect of repeated periods of ODM management during lactation. Goats at the
      beginning of both experiments were at 25 d in milk on average and were previously
      milked twice daily (twice-daily milking; TDM). In experiment 1, which was
      conducted for 2 periods (P) of 9 wk (P1, P2), 48 goats were grouped (1, 2, 3, and
      4) according to milk yield, parity, and somatic cell count (SCC). Over the 2
      periods, goats from group 1 were managed with TDM and those from group 2 were
      managed with ODM. In group 3, goats were assigned to TDM during P1 and ODM during
      P2, conversely, those in group 4 were assigned to ODM in P1 and TDM in P2. During
      P1, the 12 goats from group 3 underwent 2 distinct morning machine milkings to
      measure milk repartition (cisternal and alveolar) in the udder based on the
      "atosiban method." On P1 plus the P2 period of 18 wk, milk loss caused by ODM
      (compared with TDM) was 16%. In our condition of 24-h milk accumulation, there
      was no correlation between milk loss and udder cisternal size. Milk fat content,
      fat globule size, or apparent laboratory cheese yield was not modified by ODM,
      but milk protein content (+2.7 g/kg), casein (+1.8 g/kg), milk soluble protein
      concentration (+1.0 g/kg), and SCC increased, whereas lipolysis decreased (-0.3
      mEq/100 g of oleic acid). In experiment 2, which was conducted for 4 periods (P1,
      P2, P3, P4) of 5 wk each, 8 goats, blocked into 2 homogenous groups (5 and 6),
      were used to study the effects of a double inversion of milking frequency (TDM or
      ODM) for 20 wk of lactation. Milk loss was 17% and ODM did not modify milk fat or
      protein contents, SCC, casein, or milk soluble protein concentration, but
      lipolysis was decreased (-0.3 mEq/100 g of oleic acid). Neither experiment showed
      the effects of period of ODM management on milk yield, milk fat or protein
      content, SCC, fat globule size, lipolysis, casein, milk soluble protein
      concentration, or apparent laboratory cheese yield.

PMID- 19841208
TI  - Comparison of reproductive performance in lactating dairy cows bred by natural
      service or timed artificial insemination.
AB  - The objective of this study was to compare reproductive performance of lactating
      dairy cows bred by natural service (NS) or timed AI (TAI). One thousand fifty
      five cows were blocked by parity and enrolled to receive either NS or TAI. Cows
      in both groups were presynchronized with 2 injections of PGF(2alpha) given at 42
      and 56 d postpartum. Fourteen days after the last PGF(2alpha) injection, cows in
      the TAI group were enrolled in an Ovsynch protocol (d 0 GnRH; 7 d later,
      PGF(2alpha); 56 h after PGF(2alpha) injection, second dose of GnRH; and 16 h
      after second GnRH cows were TAI). Cows in the TAI group were resynchronized with
      an intravaginal insert containing progesterone inserted 18 d after TAI and
      removed 7 d later when GnRH was given. Cows were examined by ultrasonography on d
      32 after TAI; nonpregnant cows received PGF(2alpha) and GnRH 56 h later followed
      by TAI 16 h after the GnRH injection. Nonpregnant cows in TAI group were
      reinseminated up to 5 times using the same scheme. Cows in the NS group were
      exposed to bulls 14 d after the second PGF(2alpha) injection, and ultrasonography
      was performed 42 d after exposure to bulls to determine pregnancy status.
      Nonpregnant cows in the NS group were reexamined by transrectal palpation
      combined with ultrasound every 28 d until diagnosed pregnant or 223 d postpartum,
      whichever occurred first. Cows diagnosed pregnant in TAI or NS were reconfirmed
      28 d later to determine pregnancy loss. All bulls underwent an evaluation of
      breeding soundness and were rested for 14 d after 14 d of cow exposure. Health
      disorders were evaluated up to 70 d postpartum, and body condition score was
      evaluated at d 70 postpartum. Blood was collected on d 56 and 65 postpartum and
      analyzed for progesterone to determine cyclicity. The proportion of pregnant cows
      in the first 21 d of breeding did not differ between groups. The overall 21-d
      cycle pregnancy rate (PR), which included a total of 8 and 5 service
      opportunities for NS and TAI, respectively, was not different between groups
      (25.7 and 25.0% for NS and TAI, respectively). The daily rate of pregnancy was
      15% greater for NS than TAI because cows in NS had a greater PR, which resulted
      in fewer median days open (111 vs. 116 d). Proportion of pregnant cows at 223 d
      postpartum was greater in the NS than TAI group (84.2 vs. 74.8%, respectively).
      Cyclicity did not affect reproductive performance. Cows with body condition score
      >/=2.75 had greater proportion of pregnant cows in the first 21 d of breeding and
      daily PR in the first 223 d postpartum Primiparous cows had greater proportion of
      pregnant cows and daily PR than multiparous cows at 223 d postpartum. In
      conclusion, the greater proportion of pregnant cows in the NS group was
      attributed to more opportunities for breeding than in the TAI group.

PMID- 19841209
TI  - Experimentally induced intramammary infection with multiple strains of
      Streptococcus uberis.
AB  - The effect of infusing a mixture of 5 Streptococcus uberis strains into mammary
      quarters of 10 lactating cows was investigated. All 5 strains, which included 2
      originally isolated from the dairy environment and 3 from clinical cases of
      mastitis, were capable of establishing an intramammary infection when infused
      individually. However, when the 5 strains were infused together, a single strain
      predominated in 7 out of 10 quarters. One strain in particular prevailed in 4
      mammary quarters and was also found to inhibit the growth of the other 4 strains
      with deferred antagonism on esculin blood agar. The genes required for the
      production of bacteriocins nisin U and uberolysin were identified in this strain,
      whereas the other 4 strains contained only uberolysin genes. Direct competition
      may have occurred between strains within the mammary gland but competition was
      not apparent when cultured together in UHT milk, where no strain predominated.
      Although the mechanism is unknown, these results imply that a selection process
      can occur within the mammary gland, leading to a single strain that is detected
      upon diagnosis of mastitis.

PMID- 19841210
TI  - Risk factors for lameness in freestall-housed dairy cows across two breeds,
      farming systems, and countries.
AB  - Lameness poses a considerable problem in modern dairy farming. Several new
      developments (e.g., herd health plans) strive to help farmers improve the health
      and welfare of their herd. It was thus our aim to identify lameness risk factors
      common across regions, breeds, and farming systems for freestall-housed dairy
      cows. We analyzed data from 103 nonorganic and organic dairy farms in Germany and
      Austria that kept 24 to 145 Holstein Friesian or Fleckvieh cows in the milking
      herd (mean = 48). Data on housing, management, behavior, and lameness scores for
      a total of 3,514 cows were collected through direct observations and an
      interview. Mean lameness prevalence was 34% (range = 0-81%). Data were analyzed
      applying logistic regression with generalized estimating equations in a split
      sample design. The final model contained 1 animal-based parameter and 3 risk
      factors related to lying as well as 1 nutritional animal-based parameter, while
      correcting for the significant confounders parity and data subset. Risk for
      lameness increased with decreasing lying comfort, that is, more frequent abnormal
      lying behavior, mats or mattresses used as a stall base compared with deep-bedded
      stall bases, the presence of head lunge impediments, or neck rail-curb diagonals
      that were too short. Cows in the lowest body condition quartile (1.25-2.50 for
      Holstein Friesian and 2.50-3.50 for Fleckvieh) had the highest risk of being
      lame. In cross-validation the model correctly classified 71 and 70% of
      observations in the model-building and validation samples, respectively. Only 2
      out of 15 significant odds ratios (including contrasts) changed direction. They
      pertained to the 2 variables with the highest P-values in the model. In
      conclusion, lying comfort and nutrition are key risk areas for lameness in
      freestall-housed dairy cows. Abnormal lying behavior in particular proved to be a
      good predictor of lameness risk and should thus be included in on-farm protocols.
      The study is part of the European Commission's Welfare Quality project.

PMID- 19841211
TI  - Prevalence and risk factors for skin lesions on legs of dairy cattle housed in
      freestalls in Norway.
AB  - Appropriate indoor housing facilities for dairy cattle promote improved animal
      welfare. Skin alterations are an indicator of dysfunctional housing. The purpose
      was to determine the relationship between different housing design and skin
      lesions, hence providing farmers more insight into how to reduce the occurrence
      of lesions. A cross-sectional study was conducted on 2,335 animals in 232
      Norwegian freestall-housed dairy cattle from September 2006 to June 2007. A model
      was established to investigate risk factors related to the presence of lesions
      including hair loss, swelling, and wounds on the legs of dairy cattle. Separate
      models were developed to investigate risk factors related to the presence of knee
      and hock lesions. Previously described risk factors were included in the models,
      together with a questionnaire addressing the attitude of the farmer toward the
      animals. Mean (+/- SD) prevalence for hock lesions was 60.5 +/- 21.2% with a
      median value of 64%. The prevalence for knee lesions was 35.3 +/- 25.7% with a
      median of 30%. Cows in herds with a soft freestall base had an odds ratio (OR)
      for knee and hock lesions of 0.22 (0.06 to 0.73) and 0.62 (0.48 to 0.80),
      respectively, compared with those in herds with a harder freestall base, such as
      concrete and compact rubber mats. There was an increased risk of hock lesions
      when the length in the lying area in a double-row freestall was >250 cm (OR =
      2.96; 1.02 to 8.60) compared with </=250 cm, and when the length of the lying
      area against a wall was >260 cm (OR = 2.11; 1.53 to 2.90) compared with < or =260
      cm. The risk for knee lesions increased if a row against a wall was >270 cm (OR =
      1.72; 1.09 to 2.72) compared with < or =270 cm. Hock lesions were associated with
      lame cows (OR = 5.76; 1.14 to 29.18) versus nonlame cows, and with cows in their
      second or higher parity (OR = 1.27; 1.06 to 1.52) versus cows in their first
      parity. Knee lesions were associated with farmers' negative attitudes toward
      animals in pain (OR = 3.28; 1.79 to 6.03) versus those with positive attitudes;
      cows in the beginning of their lactation (OR = 1.84; 1.24 to 2.74) versus those
      at the end of their lactation; and tall animals (OR = 1.27; 1.00 to 1.61) versus
      shorter animals. These results show that freestall design is important with
      respect to skin lesions as are the characteristics of individual animals and the
      farmer.

PMID- 19841212
TI  - Cow preference and usage of free stalls compared with an open pack area.
AB  - Free-stall housing systems are designed to provide a comfortable and hygienic
      lying area, but some aspects of stall design may restrict usage by cows. The aim
      of this study was to compare free-stall housing with a comparable lying area
      (open pack) without stall partitions. We predicted that cows would spend more
      time lying down and standing in the bedded area when provided access to an open
      pack than when in free stalls. We also predicted that cows would spend less time
      standing outside of the lying area and less time perching with the front 2 hooves
      in the lying area when using the open pack. Groups (n = 8) of 12 cows each were
      provided access to either the open pack or stalls. After a 7-d adaptation period,
      each group was tested sequentially in the 2 treatments for 3 d each. This no
      choice phase was followed by an 8-d choice phase during which cows had
      simultaneous access to both treatments. During the no-choice phase, cows spent
      more time lying down (13.03 +/- 0.24 vs. 12.48 +/- 0.24 h/d) and standing with
      all 4 hooves in the bedded area (0.96 +/- 0.12 vs. 0.41 +/- 0.12 h/d) of the open
      pack than in the stalls. During the choice phase, cows spent more time lying down
      (7.20 +/- 0.29 vs. 5.86 +/- 0.29 h/d) and standing with all 4 hooves in the
      bedded area (0.58 +/- 0.07 vs. 0.12 +/- 0.07 h/d) of the open pack than in the
      stalls. In both the no-choice (1.66 +/- 0.24 vs. 0.55 +/- 0.24 h/d) and choice
      (0.55 +/- 0.07 vs. 0.29 +/- 0.07 h/d) phases, cows spent more time standing with
      just 2 hooves in the stalls than in the open pack. In conclusion, cows spent more
      time lying and standing with all 4 hooves in the bedded open pack than in the
      stalls. Additionally, cows spent more time standing in the alley and standing
      with just the front 2 hooves on the bedding in the stalls than in the bedded open
      pack; increased standing time on wet concrete is a known risk factor for
      lameness.

PMID- 19841213
TI  - Effect of recombinant bovine somatotropin and a shortened or no dry period on the
      performance of lactating dairy cows.
AB  - The objective of this study was to determine the effects of altering dry period
      length in multiparous dairy cows (n = 341) on milk production for a full
      lactation (294 d). The study used 3 commercial herds in the western United
      States. Cows producing greater than 8,400 kg of mature-equivalent milk were
      assigned to treatments 60 d before their due dates. The 4 treatments were 1) 60-d
      dry period, label use of recombinant bovine somatotropin (rbST; 60d-L); 2) 32-d
      dry period, label use of rbST (32d-L); 3) 0-d dry period, label use of rbST (0d
      L); and 4) 0-d dry period, continuous use of rbST (0d-C). Cows with shortened dry
      periods produced 625, 1,000, and 1,042 kg of milk during the prepartum period for
      treatments 2 to 4, respectively. During the postpartum period, cows on the 32d-L
      treatment produced similar amounts of milk compared with the 60d-L treatment
      (11,490 vs. 11,968 kg, respectively). However, cows on the 0d-L (10,316 kg) and
      0d-C (10,195 kg) treatments produced significantly lower amounts of milk during
      the postpartum period compared with the 60d-L treatment. Total milk production
      from the prepartum and postpartum periods was not altered significantly and was
      11,974, 12,112, 11,310, and 11,230 kg for treatments 1 to 4, respectively. The
      concentrations of beta-hydroxybutyrate and nonesterified fatty acids in serum
      after calving were decreased for cows on the 32d-L, 0d-L, and 0d-C treatments
      compared with cows on the 60d-L treatment, which may indicate improved metabolic
      status.

PMID- 19841214
TI  - Difference in the nature of tannins on in vitro ruminal methane and volatile
      fatty acid production and on methanogenic archaea and protozoal populations.
AB  - Six plant sources of hydrolyzable tannins (HT) or HT and condensed tannins (CT;
      designated as HT1, HT2, HT3, HT + CT1, HT + CT2, and HT + CT3) were evaluated to
      determine their effects in vitro on CH(4) production and on ruminal archaeal and
      protozoa populations, and to assess potential differences in biological
      activities between sources containing HT only or HT and CT. Samples HT1, HT2, and
      HT3 contained only HT, whereas samples HT + CT1, HT + CT2, and HT + CT3 contained
      HT and CT. In experiment 1, in vitro incubations with samples containing HT or HT
      + CT resulted in a decrease in CH(4) production of 0.6 and 5.5%, respectively,
      compared with that produced by incubations containing the added tannin binder
      polyethylene glycol-6000. Tannin also suppressed the population of methanogenic
      archaea in all incubations except those with HT2, with an average decrease of
      11.6% in HT incubations (15.8, 7.09, and 12.0 in HT1, HT2, and HT3) and 28.6% in
      incubations containing HT + CT (35.0, 40.1, and 10.8 in HT + CT1, HT + CT2, and
      HT + CT3) when compared with incubations containing added polyethylene glycol
      6000. The mean decrease in protozoal counts was 12.3% in HT and 36.2% in HT + CT
      incubations. Tannins increased in vitro pH, reduced total VFA concentrations,
      increased propionate concentrations, and decreased concentrations of iso-acids.
      In experiment 2, when a basal diet was incubated with graded levels of HT + CT1,
      HT + CT2, and HT + CT3, the total gas and CH4 production and archaeal and
      protozoal populations decreased as the concentration of tannins increased. Our
      results confirm that tannins suppress methanogenesis by reducing methanogenic
      populations in the rumen either directly or by reducing the protozoal population,
      thereby reducing methanogens symbiotically associated with the protozoal
      population. In addition, tannin sources containing both HT and CT were more
      potent in suppressing methanogenesis than those containing only HT.

PMID- 19841215
TI  - Isolipidic additions of fat from corn germ, corn distillers grains, or corn oil
      in dairy cow diets.
AB  - Eight multiparous and 8 primiparous Holstein cows were used in a replicated 4 x 4
      Latin square design with 4-wk periods to determine the effects on dairy cow
      performance of feeding corn germ (CG) compared with dried distillers grains with
      solubles (DDGS) or corn oil (CO). Four isolipidic dietary treatments were
      formulated: a control diet, a 14% corn germ diet (CGD), a 30% dry distillers
      grains with solubles diet (DGD), and a 2.5% corn oil diet (COD). All diets were
      formulated to contain 6.0% fat, with the fat in the control diet provided by a
      ruminally inert fat source. Dry matter intake was decreased by feeding the COD
      compared with the CGD; however, no difference in dry matter intake was observed
      among the control diet, the DGD, and the COD. Dietary treatments had no effect on
      milk yield, energy-corrected milk, or 4% fat-corrected milk. Feeding CG had no
      effect on milk fat percentage when compared with the control diet; however, milk
      fat percentage tended to decrease with DDGS and decreased with CO when compared
      with the CGD. Milk protein percentage decreased when cows were fed the COD
      compared with the control diet. Feeding CO tended to decrease milk fat yield
      compared with CG; however, dietary treatments had no effect on milk protein and
      lactose yield. Feed efficiency was not affected by dietary treatments and
      averaged 1.55 kg of energy-corrected milk/kg of dry matter intake. Feeding DDGS
      and CO increased the concentration of vaccenic and conjugated linoleic acid in
      milk fat. Concentrations of monounsaturated and polyunsaturated fatty acids in
      milk were increased in response to feeding the 3 corn coproducts. Fat from CG
      appears to be relatively protected in the rumen when compared with that from DDGS
      and CO and therefore will not affect the production of milk fat to the degree of
      the more available fat in DDGS and CO.

PMID- 19841216
TI  - Changes of immunophysiological characteristics in neonatal calves experimentally
      challenged with mixture of live bacteria and virus.
AB  - The aim of the present study was to define efficient immunophysiological
      parameters in neonatal Holstein calves with an experimentally induced microbial
      infection. Calves (n = 15) were challenged with classical swine fever virus (LOM
      strain) and Erysipelothrix insidiosa live vaccine by intravenous injection at 3
      wk of age except for control calves (n = 4). The level of total serum IgA was
      significantly increased at 14 and 19 d post-experimental challenge (DPEC)
      compared with that in calves at -2 DPEC. At 5 DPEC, relative amounts of bacterial
      and viral-specific IgA increased significantly and were sustained until 26 DPEC.
      In the hematology assay, the neutrophil:lymphocyte ratio (%) in whole blood was
      significantly decreased at 14 DPEC because of a significant increase in
      lymphocytes and a coincident decrease in neutrophils. The percentages of CD4+ and
      CD25+ T cells were significantly decreased at 14 DPEC and returned to initial
      levels at 19 DPEC. It is intriguing to note that the level of serum lactoferrin
      was significantly decreased by the microbial challenge within 1 d. The
      concentration of haptoglobin was increased within 3 d and gradually decreased in
      calves after microbial challenge. Our results suggest that 1) bovine serum
      lactoferrin plays an important role in the innate immune response against
      microbial infection at an early stage and 2) experimentally induced microbial
      challenge using porcine live bacterial and viral vaccine in calves could be a
      good experimental model to evaluate the effect of diet or stress induced by
      environmental change on the immune responses against microbial infection.

PMID- 19841217
TI  - Whole intact rapeseeds or sunflower oil in high-forage or high-concentrate diets
      affects milk yield, milk composition, and mammary gene expression profile in
      goats.
AB  - This study aimed to ascertain the response of goat mammary metabolic pathways to
      concentrate and lipid feeding in relation to milk fatty acid (FA) composition and
      secretion. Sixteen midlactation multiparous goats received diets differing in
      forage-to-concentrate ratio [high forage (HF) 64:36, and low forage (LF) 43:57]
      supplemented or not with lipids [HF with 130 g/d of oil from whole intact
      rapeseeds (RS) and LF with 130 g/d of sunflower oil (SO)] in a 4 x 4 Latin square
      design. Milk yield, milk composition, FA profile, and FA secretion were measured,
      as well as the expression profiles of key genes in mammary metabolism and of
      8,382 genes, using a bovine oligonucleotide microarray. After 3 wk of treatment,
      milk, lactose, and protein yields were lower with HF-RS than with the other
      diets, whereas treatment had no effect on milk protein content. Milk fat content
      was higher with the HF-RS and LF-SO diets than with the HF and LF diets, and SO
      supplementation increased milk fat yield compared with the LF diet. Decreasing
      the forage-to-concentrate ratio from 64:36 to 43:57 had a limited effect on goat
      milk FA concentrations and secretions. Supplementing the LF diet with SO changed
      almost all the FA concentrations, including decreases in medium-chain saturated
      FA and large increases in trans C18:1 and C18:2 isomers (particularly trans-11
      C18:1 and cis-9, trans-11 conjugated linoleic acid), without significant changes
      in C18:0 and cis-9 C18:1, whereas supplementing the HF diet with RS led to a
      strong decrease in short- and medium-chain saturated FA and a very strong
      increase in C18:0 and cis-9 C18:1, without significant changes in trans C18:1 and
      conjugated linoleic acid. Despite the decreases in milk lactose and protein
      yields observed with HF-RS, and despite the decrease in milk medium-chain FA and
      the increase in C18 FA secretion with RS or SO supplementation, none of the
      dietary treatments had any effect on mammary mRNA expression of the key genes
      involved in lactose (e.g., alpha-lactalbumin), protein (e.g., beta-casein), and
      lipid metabolism (e.g., lipoprotein lipase) after 3 wk of treatment. In addition,
      transcriptome analysis did not provide evidence of treatments inducing
      significant changes in the expression of specific genes in the mammary gland.
      However, 2-way hierarchical clustering analysis highlighted different global
      mammary expression profiles between diets, showing that the gene expression
      profiles corresponding to the same diet were gathered by common groups of genes.
      This experiment suggests that after 3 wk of dietary treatment, other factors,
      such as substrate availability for mammary metabolism, could play an important
      role in contributing to milk FA responses to changes in diet composition in the
      goat.

PMID- 19841218
TI  - Effect of lauric acid and coconut oil on ruminal fermentation, digestion, ammonia
      losses from manure, and milk fatty acid composition in lactating cows.
AB  - This experiment (replicated 3 x 3 Latin square design) was conducted to
      investigate the effects of lauric acid (LA) or coconut oil (CO) on ruminal
      fermentation, nutrient digestibility, ammonia losses from manure, and milk fatty
      acid (FA) composition in lactating cows. Treatments consisted of intraruminal
      doses of 240 g of stearic acid/d (SA; control), 240 g of LA/d, or 530 g of CO/d
      administered once daily, before feeding. Between periods, cows were inoculated
      with ruminal contents from donor cows and allowed a 7-d recovery period.
      Treatment did not affect dry matter intake, milk yield, or milk composition.
      Ruminal pH was slightly increased by CO compared with the other treatments,
      whereas LA and CO decreased ruminal ammonia concentration compared with SA. Both
      LA and CO decreased protozoal counts by 80% or more compared with SA. Methane
      production rate in the rumen was reduced by CO compared with LA and SA, with no
      differences between LA and SA. Treatments had no effect on total tract apparent
      dry matter, organic matter, N, and neutral detergent fiber digestibility
      coefficients or on cumulative (15 d) in vitro ammonia losses from manure.
      Compared with SA, LA and CO increased milk fat 12:0, cis-9 12:1, and trans-9 12:1
      content and decreased 6:0, 8:0, 10:0, cis-9 10:1, 16:0, 18:0, cis 18:1, total
      18:2, 18:3 n-3 and total polyunsaturated FA concentrations. Administration of LA
      and 14:0 (as CO) in the rumen were apparently transferred into milk fat with a
      mean efficiency of 18 and 15%, respectively. In conclusion, current data
      confirmed that LA and CO exhibit strong antiprotozoal activity when dosed
      intraruminally, an effect that is accompanied by decreases in ammonia
      concentration and, for CO, lowered methane production. Administration of LA and
      CO in the rumen also altered milk FA composition.

PMID- 19841219
TI  - From milk to diet: feed recognition for milk authenticity.
AB  - The presence of plastidial DNA fragments of plant origin in animal milk samples
      has been confirmed. An experimental plan was arranged with 4 groups of goats,
      each provided with a different monophytic diet: 3 fresh forages (oats, ryegrass,
      and X-triticosecale) and one 2-wk-old silage (X-triticosecale). Feed-derived
      rubisco (ribulose bisphosphate carboxylase, rbcL) DNA fragments were detected in
      100% of the analyzed goat milk samples, and the nucleotide sequence of the PCR
      amplified fragments was found to be 100% identical to the corresponding fragments
      amplified from the plant species consumed in the diet. Two additional chloroplast
      based molecular markers were used to set up an assay for distinctiveness,
      conveniently based on a simple PCR. In one case, differences in single
      nucleotides occurring within the gene encoding for plant maturase K (matK) were
      exploited. In the other, plant species recognition was based on the difference in
      the length of the intron present within the transfer RNA leucine (trnL) gene. The
      presence of plastidial plant DNA, ascertained by the PCR-based amplification of
      the rbcL fragment, was also assessed in raw cow milk samples collected directly
      from stock farms or taken from milk sold on the commercial market. In this case,
      the nucleotide sequence of the amplified DNA fragments reflected the multiple
      forages present in the diet fed to the animals.

PMID- 19841221
TI  - Varying forage type, metabolizable protein concentration, and carbohydrate source
      affects manure excretion, manure ammonia, and nitrogen metabolism of dairy cows.
AB  - Effects of forage source, concentration of metabolizable protein (MP), and type
      of carbohydrate on manure excretion by dairy cows and production of ammonia from
      that manure were evaluated using a central composite experimental design. All
      diets (dry basis) contained 50% forage that ranged from 25:75 to 75:25 alfalfa
      silage:corn silage. Diets contained 10.7% rumen-degradable protein with variable
      concentrations of undegradable protein so that dietary MP ranged from 8.8 to 12%.
      Starch concentration ranged from 22 to 30% with a concomitant decrease in neutral
      detergent fiber. A total of 15 diets were fed to 36 Holstein cows grouped in 6
      blocks. Each block was a replicated 3 x 3 Latin square resulting in 108
      observations. Manure output (urine and feces) was measured using total
      collection, and fresh feces and urine were combined into slurries and incubated
      for 48 h to measure NH3-N production. Feces, urine, and manure output averaged
      50.5, 29.5, and 80.1 kg/d, respectively. Manure output increased with increasing
      dry matter intake (approximately 3.5 kg of manure/kg of dry matter intake),
      increased concentrations of alfalfa (mostly via changes in urine output), and
      decreased concentrations of starch (mostly via changes in fecal output). The
      amount of NH3-N produced per gram of manure decreased with increasing alfalfa
      because excreted N shifted from urine to feces. Increasing MP increased NH3-N
      produced per gram of manure mainly because of increased urinary N, but increased
      fecal N also contributed to the manure NH3. Manure NH3-N production per cow
      (accounts for effects on manure production and NH3-N produced per unit of manure)
      was least and milk protein yields were maximal for diets with high alfalfa (75%
      of the forage), moderate MP (11% of diet dry matter), and high starch (30% of
      diet dry matter).

PMID- 19841220
TI  - Varying type of forage, concentration of metabolizable protein, and source of
      carbohydrate affects nutrient digestibility and production by dairy cows.
AB  - The effects of forage source, concentration of metabolizable protein (MP), type
      of carbohydrate, and their interactions on nutrient digestibility and production
      were evaluated using a central composite treatment design. All diets (dry basis)
      contained 50% forage that ranged from 25:75 to 75:25 alfalfa silage:corn silage.
      Rumen-degradable protein comprised 10.7% of the dry matter (DM) in all diets, but
      undegradable protein ranged from 4.1 to 7.1%, resulting in dietary MP
      concentrations of 8.8 to 12.0% of the DM. Dietary starch ranged from 22 to 30% of
      the DM with a concomitant decrease in neutral detergent fiber concentrations. A
      total of 15 diets were fed to 36 Holstein cows grouped in 6 blocks. Each block
      consisted of three 21-d periods, and each cow was assigned a unique sequence of 3
      diets, resulting in 108 observations. Milk production and composition, feed
      intake, and digestibility of major nutrients (via total collection of feces and
      urine) were measured. Few significant interactions between main effects were
      observed. Starch concentration had only minor effects on digestibility and
      production. Replacing corn silage with alfalfa decreased digestibility of N but
      increased digestibility of neutral detergent fiber. Increasing the concentration
      of MP increased N digestibility. The concentration (Mcal/kg) of dietary
      digestible energy (DE) increased linearly as starch concentration increased (very
      small effect) and was affected by a forage by MP interaction. At low MP, high
      alfalfa reduced DE concentration, but at high MP, increasing alfalfa increased DE
      concentration. Increasing alfalfa increased DM and DE intakes, which increased
      yields of energy-corrected milk, protein, and fat. Increasing MP increased yields
      of energy-corrected milk and protein. The response in milk protein to changes in
      MP was much less than predicted using the National Research Council (2001) model.

PMID- 19841222
TI  - Effects of feeding grass or red clover silage cut at two maturity stages in dairy
      cows. 1. Nitrogen metabolism and supply of amino acids.
AB  - This study investigated the effects of plant species (red clover vs. timothy
      meadow fescue) and forage maturity at primary harvest (early vs. late cut silage)
      on rumen fermentation, nutrient digestion, and nitrogen metabolism including
      omasal canal AA flow and plasma AA concentration in lactating cows. Five dairy
      cows equipped with rumen cannulas were used in a study designed as a 5 x 5 Latin
      square with 21-d periods. The diets consisted of early-cut and late-cut grass and
      red clover silage, respectively, and a mixture of late-cut grass and early-cut
      red clover silages given ad libitum with 9 kg/d of a standard concentrate. Grass
      silage dry matter intake tended to decrease but that of red clover silages tended
      to increase with advancing maturity. Milk yields were unchanged among treatments,
      milk protein and fat concentrations being lower for red clover than for grass
      silage diets. Rumen fluid pH was unchanged but volatile fatty acid and ammonia
      concentrations were higher for red clover than for grass silage diets. Intake of
      N, and omasal canal flows of total nonammonia N (NAN), microbial NAN, and dietary
      NAN were higher for red clover than for grass silage diets but were not affected
      by forage maturity. However, microbial NAN flow and amount of N excreted in the
      feces decreased with advancing maturity for grass diets but increased for red
      clover diets. Apparent ruminal N degradability of the diets was unchanged, but
      true ruminal N degradability decreased and efficiency of microbial synthesis
      increased with red clover diets compared with grass silage diets. Omasal canal
      flows of AA, except those for Met and Cys, were on average 20% higher for red
      clover than grass silage diets. Omasal canal digesta concentrations of Leu, Phe,
      branched-chain, and essential AA were higher but those of Met lower for red
      clover than for grass silage diets. Plasma AA concentrations, except for His
      (unchanged) and Met (lower), were higher for red clover than for grass diets.
      However, none of these AA-related variables were affected by forage maturity.
      Total digestibility of N and excretion of N in the urine were higher for red
      clover than for grass diets and decreased with advancing maturity. It was
      concluded that despite the higher total AA supply of cows fed red clover versus
      grass silage diets, further milk production responses on red clover diets were
      compromised by an inadequate supply of Met as evidenced by lower Met
      concentration in the AA profile of omasal digesta and plasma.

PMID- 19841223
TI  - Effects of feeding grass or red clover silage cut at two maturity stages in dairy
      cows. 2. Dry matter intake and cell wall digestion kinetics.
AB  - This study examined the effects of red clover or grass silages cut at 2 stages of
      growth on feed intake, cell wall digestion, and ruminal passage kinetics in
      lactating dairy cows. Five dairy cows equipped with rumen cannulas were used in a
      study designed as a 5 x 5 Latin square with 21-d periods. Diets consisted of
      early-cut and late-cut grass and red clover silages and a mixture of late-cut
      grass and early-cut red clover silages offered ad libitum. All diets were
      supplemented with 9 kg/d of concentrate. Ruminal digestion and passage kinetics
      were assessed by the rumen evacuation technique. Apparent total-tract
      digestibility was determined by total fecal collection. The silage dry matter
      intake was highest when the mixed forage diet was fed and lowest with the early
      cut red clover diet. Delaying the harvest tended to decrease DMI of grass and
      increase that of red clover. The intake of neutral detergent fiber (NDF) and
      potentially digestible NDF (pdNDF) was lower but the intake of indigestible NDF
      (iNDF) was higher for red clover diets than for grass diets. The rumen pool size
      of iNDF and the ratio of iNDF to pdNDF in the rumen contents were larger, and
      pool sizes of NDF and pdNDF were smaller for red clover than for grass silage
      diets. Outflow of iNDF and the ratio of iNDF to pdNDF in digesta entering the
      omasal canal were larger, and the outflow of pdNDF was smaller for red clover
      than for grass silage diets. The digestion rate (k(d)) of pdNDF was faster for
      red clover diets than for grass silage diets. Delaying the harvest decreased k(d)
      for grass but increased it for red clover silage diets. Observed differences in
      fiber characteristics of red clover and grass silages were reflected in ruminal
      digestion and passage kinetics of these forages. The low intake of early-cut red
      clover silage could not be explained by silage digestibility, fermentation
      quality, or rumen fill, but was most likely related to nutritionally suboptimal
      composition because inclusion of moderate quality grass silage improved silage
      intake. Increasing the maturity of ensiled red clover does not seem to affect
      silage dry matter intake as consistently as that of grasses.

PMID- 19841224
TI  - Increasing intravenous infusions of glucose improve body condition but not
      lactation performance in midlactation dairy cows.
AB  - The present study was intended to test whether intravenously applied glucose
      would elicit dose effects on lactation performance similar to those observed
      after gastrointestinal glucose application. Six midlactation cows received
      intravenous glucose infusions (GI), increasing by 1.25% of the calculated net
      energy for lactation (NE(L)) requirement per day, whereas control cows received
      volume-equivalent saline infusions (SI). Measurements and samples were taken at
      surplus glucose dose levels of 0, 10, 20, and 30% of the NE(L) requirement,
      respectively. Body weight and backfat thickness increased linearly with
      increasing glucose dose for cows on GI compared with SI. No differences were
      observed in daily feed intake, milk energy output, and energy-corrected milk
      yield between treatments. However, milk protein percentage and yield increased
      linearly with the dose of glucose infused in the GI group. Although milk lactose
      was not affected by treatment during the infusion period, milk lactose percentage
      and yield decreased for GI, but not SI, once infusions ceased. Based on 5 diurnal
      blood samples, daily mean and maximum concentrations of plasma glucose and serum
      insulin showed linear increases with increasing GI, whereas their daily minimum
      concentrations were unaffected. At GI of 30% of the NE(L) requirement, marked
      hyperglycemia and hyperinsulinemia were observed at 1600 h (i.e., 1 h
      postprandially), coinciding with glucosuria. The revised quantitative insulin
      sensitivity check index indicated linear development of insulin resistance for
      the GI treatment but no such change in SI cows. Glucose infusion decreased daily
      mean and maximum serum beta-hydroxybutyrate and daily minimum nonesterified fatty
      acid concentrations relative to SI, whereas serum urea nitrogen was only
      numerically decreased by GI. No changes were observed in the serum activities of
      gamma-glutamyl transferase and aspartate transaminase and in the serum
      concentrations of bilirubin and macrominerals. However, serum phosphorus
      concentration increased after withdrawal of GI, but not SI. Only in GI cows did
      glycogen content increase or tend to increase linearly in the liver and skeletal
      muscle. In conclusion, midlactation dairy cows on an energy-balanced diet
      directed intravenously infused glucose predominantly to body fat reserves rather
      than increasing lactation performance. This may suggest that the metabolic fate
      of glucose is modified by metabolic signals, hormonal signals, or both from the
      portal-drained viscera when absorbed from the intestine.

PMID- 19841225
TI  - Influence of detachment procedure and diet on recovery of solid-associated
      bacteria from sheep ruminal digesta and representativeness of bacterial isolates
      as assessed by automated ribosomal intergenic spacer analysis-polymerase chain
      reaction.
AB  - Six ruminally and duodenally cannulated sheep were used in a partially replicated
      4 x 4 Latin square experiment designed to evaluate the efficiency of 3 detachment
      procedures (DP) to recover solid-associated bacteria (SAB) from ruminal digesta.
      The 4 experimental diets contained forage to concentrate (F:C) ratios of 70:30 or
      30:70 with either alfalfa hay or grass hay as the forage. Bacterial biomass was
      labeled with 15NH4Cl. The DP were 1) MET: digesta was incubated at 38 degrees C
      for 15 min with saline solution (0.9% NaCl) containing 0.1% methylcellulose under
      continuous shaking; 2) STO: digesta was mixed with cold saline solution and
      homogenized with a stomacher for 5 min at 230 rpm; 3) FRE: digesta was
      immediately frozen at -20 degrees C for 72 h, thawed at 4 degrees C, mixed with
      saline solution and subjected to STO procedure. Common to all treatments was
      storing at 4 degrees C for 24 h after the treatment, homogenization, filtration,
      and resuspension of digesta 2 times in the treatment solutions. The automated
      ribosomal intergenic spacer analysis of the 16S ribosomal DNA was used to analyze
      the similarity between bacterial communities attached to the digesta and those in
      the pellet obtained after each DP. There were no significant F:C x DP or forage x
      DP interactions for any variable. On average, STO treatment detached 65.8% of SAB
      from ruminal digesta, about 1.2 and 1.5 times more than FRE and MET treatments,
      respectively. Total recovery of SAB in STO pellets (48.9%) was greater compared
      with FRE (31.7%) and MET (33.1%), values being greater for high-forage compared
      with high-concentrate diets. Similarity index between the bacteria attached to
      digesta and those in the pellets were lower for FRE (48.2%) compared with MET
      (54.1%) and STO (54.1%), which suggests that FRE could have destroyed cell
      integrity of some bacterial species, thus reducing the bacterial diversity
      present in the pellets. The STO method was the most effective removing SAB from
      digesta, but only a moderate similarity between the bacterial communities
      attached to digesta and those recovered in the bacterial pellets was obtained.
      Values of duodenal microbial flow estimated using SAB as reference bacteria were
      greater with FRE compared with STO and MET, but all DP detected similar
      differences between diets, and therefore did not influence the interpretation of
      results.

PMID- 19841226
TI  - Canola meal replacing distillers grains with solubles for lactating dairy cows.
AB  - A study was conducted to determine the response to feeding diets containing
      canola meal (CM) as a protein supplement in place of all or portions of dried
      distillers grains with solubles (DDGS). Twelve lactating Holstein cows (4
      primiparous and 8 multiparous) were fed in a 4 x 4 Latin square design over 4-wk
      periods. Data were collected wk 3 and 4 of each period. Diets were formulated in
      which CM was 100, 66, 33, and 0% of the supplemental protein replacing the
      protein from DDGS. All diets (averaged 15.1% crude protein and 4.5% ether
      extract) contained 55% forage and 45% concentrate, with the forage being 50% corn
      silage and 50% alfalfa hay. Dry matter intake (25.4 kg/d) was similar for all
      diets. Milk production (35.2, 35.8, 34.5, and 34.3 kg/d, respectively, for 100,
      66, 33, and 0% CM) was similar for all diets, but tended to be greater with
      higher proportions of CM. Milk protein concentration (3.04%), fat concentration
      (3.92%), and fat yield (1.37 kg/d) were similar for all diets, whereas protein
      yield (1.08, 1.10, 1.05, and 1.03 kg/d, respectively, for 100, 66, 33, and 0% CM)
      tended to be greater with increasing amounts of CM in the diet. Feed efficiency
      (1.46 kg of energy-corrected milk/kg of dry matter intake) was similar for all
      diets. Lysine was the first limiting amino acid for milk protein synthesis when
      CM or DDGS were fed, whereas methionine was first limiting when the combination
      diets were fed. Concentrations of ammonia and volatile fatty acids in ruminal
      contents were similar for all diets. Canola meal is a suitable replacement for
      DDGS in dairy cow diets.

PMID- 19841227
TI  - Effects of anion supplementation to low-potassium prepartum diets on macromineral
      status and performance of periparturient dairy cows.
AB  - Data from multiparous Holstein cows (n = 43) were used to determine whether
      supplementation of anions to low-potassium (K) prepartum diets would improve
      periparturient energy and macromineral status and affect performance during the
      postpartum period. Beginning 21 d before expected parturition, cows were fed a
      control diet (1.29% K; +10 mEq/100 g; n = 21) or a low dietary cation-anion
      difference (DCAD) diet (1.29% K; -15 mEq/100 g; n = 22) with anions provided
      through a combination of sulfate from calcium sulfate dihydrate (0.40% S total
      ration) and chloride (1.17% Cl total ration) from SoyChlor 16-7 (West Central,
      Ralston, IA). All cows were fed the same postpartum diet from parturition through
      63 d postpartum. Feeding anions decreased overall urine pH (8.17 vs. 6.70) during
      the prepartum period. Overall, peripartum concentrations of plasma Ca, P, and Mg
      were similar between treatments; however, concentrations of plasma Ca tended to
      be increased during the first 24 h postcalving in cows fed the low DCAD diet.
      Overall, concentrations of plasma P tended to be increased by feeding the anionic
      diet prepartum; this effect was more pronounced during the immediate peripartal
      period. Anionic supplementation did not affect incidence of clinical (<5 mg/dL)
      and subclinical (5 to 8 mg/dL) hypocalcemia, clinical hypophosphatemia (<2
      mg/dL), or clinical (<1.1 mg/dL) and subclinical (1.1 to 1.8 mg/dL)
      hypomagnesemia. Nevertheless, subclinical hypophosphatemia (2 to 4 mg/dL) tended
      to be decreased at 16 h postcalving and was decreased at d 2 postpartum for cows
      fed the anionic diet prepartum. Anion supplementation decreased prepartum dry
      matter intake (15.6 vs. 14.4 kg/d), but did not affect postpartum dry matter
      intake (22.4 vs. 23.0 kg/d), milk yield (46.5 vs. 46.1 kg/d), or content and
      yield of milk fat and true protein. Plasma concentrations of energy-related
      metabolites (glucose, nonesterified fatty acids, beta-hydroxybutyrate) were
      similar for both groups during the prepartum and postpartum periods. Glucose rate
      of appearance was determined by continuous infusion of 6,6-dideuterated glucose
      in a subset of cows between 6 and 10 d prepartum (control, n = 12; low DCAD, n =
      9) and 7 and 10 d postpartum (control, n = 9; low DCAD, n = 8) periods. Glucose
      rate of appearance was not affected by treatment during the prepartum or
      postpartum periods. Overall, anion supplementation of low K diets improved P
      status during the early postpartum period, but did not affect aspects of energy
      metabolism or periparturient performance.

PMID- 19841228
TI  - Short communication: the preruminant calf as a model for characterizing the
      effects of vitamin D status in the neonate.
AB  - The objective of this study was to evaluate the feasibility of using the
      preruminant dairy calf as a model for evaluating effects of vitamin D status in
      the neonate. Because the newborn calf can be sustained during the first weeks of
      life solely on a fluid diet having a defined composition, has documented
      nutritional requirements, and is minimally affected by repeated samplings of
      peripheral blood, it has the potential to serve as a model for characterizing
      nutrient-specific effects on the growth and health of the neonate. Colostrum-fed
      Holstein bull calves (n = 13) entered the trial at approximately 4 d of age. All
      calves were fed a custom-formulated milk replacer devoid of vitamin D. Plasma 25
      hydroxyvitamin D(3) concentrations in all calves were determined on a regular
      basis beginning at d 0. Using this information, low- and high-status groups of
      calves were established by subcutaneous administration of 25-hydroxyvitamin D(3).
      To maintain targeted plasma 25-hydroxyvitamin D(3) concentrations in low (<30
      ng/mL) and high (>60 ng/mL) vitamin D-status calves, low-status calves (n = 6)
      received a total of 8,600 IU (2,225 IU/wk) of vitamin D during the experimental
      period and high-status calves (n = 7) received 54,000 IU (13,500 IU/wk).
      Concentrations of 25-hydroxyvitamin D(3) in low-status calves averaged 27 ng/mL,
      compared with 78 ng/mL in high-status calves, and were less at all sampling times
      from d 7 to d 28. Concentrations of 1,25-dihydroxyvitamin D(3) and 25
      hydroxyvitamin D(3) were not correlated. Calcium, magnesium, and phosphorous
      concentrations were unaffected by 25-hydroxyvitamin D(3) administration; however,
      plasma calcium and 1,25-dihydroxyvitamin D(3) concentrations were correlated.
      Calcium and magnesium concentrations decreased with age but remained within
      normal ranges for dairy cattle. These results indicate that it is possible to
      predictably control vitamin D status over a 28-d period and suggest that the
      preruminant calf might be useful as a model for studying effects of vitamin D on
      growth, development, and immune function in the neonate.

PMID- 19841229
TI  - Technical note: the use of a telemetric system to continuously monitor ruminal
      temperature and to predict ruminal pH in cattle.
AB  - The objective of this study was to compare a telemetric monitoring system to an
      existing in situ methodology (conventional system) of monitoring ruminal
      temperature and to validate its use to detect changes in ruminal pH (RpH). Four
      nonlactating, ruminally cannulated Holstein dairy cows (760 +/- 30 kg of body
      weight, mean +/- standard deviation) housed in a tie-stall facility were used in
      the study. The experiment was conducted during the month of May and the recorded
      ambient temperature was 8.0 +/- 2.0 degrees C (mean +/- SD). The cows were fed a
      diet consisting of chopped mixed hay (MH; 11.3% crude protein, 59.7% neutral
      detergent fiber, 17.3% nonfiber carbohydrate, 3.1% ether extract, and 11.3% ash;
      dry matter basis) during wk 1 and were gradually switched to a high-grain (HG)
      diet (11.6% crude protein, 30.2% neutral detergent fiber, 50.7% nonfiber
      carbohydrate, 3.0% ether extract, and 6.0% ash; dry matter basis) during wk 2. A
      conventional system that utilized an indwelling electrode was used to monitor RpH
      and ruminal temperature (RT(C)) during d 6 and 7 of each week. The indwelling
      electrode was attached to a telemetric bolus and ruminal temperature (RT(T)) was
      logged into a personal computer. The daily mean, minimum, and maximum RpH and
      duration (min/d) RpH <6.2 were 6.39 +/- 0.04, 6.10 +/- 0.05, 6.66 +/- 0.03, and
      107 +/- 50 during MH feeding (wk 1) and 5.84 +/- 0.03, 5.35 +/- 0.05, 6.35 +/-
      0.03, and 1,257 +/- 40 during HG feeding (wk 2), respectively, and were different
      across diets (week effect). Ruminal pH did not decrease below 5.6, 5.8, and 6.0
      during MH feeding; mean duration of RpH <5.6, <5.8, and <6.0 during HG feeding
      was 279 +/- 149, 611 +/- 139, and 894 +/- 101, respectively. Mean daily RT(C)
      increased from 37.5 degrees C +/- 0.1 in wk 1 to 38.6 degrees C +/- 0.1 in wk 2;
      there was also an increase from wk 1 to wk 2 in minimum and maximum daily RT(C)
      and durations (min/d) of RT(C) >38.0, >38.2, >38.4, and >38.6 degrees C. These
      increases were not detectable with the telemetric system. Ruminal temperature
      obtained by the conventional system was 0.68 degrees C +/- 0.005 lower than RT(T)
      during MH feeding (wk 1), whereas RT(C) was 0.04 degrees C +/- 0.004 higher than
      RT(T) during HG feeding (wk 2). Daily minimum RpH was associated with maximum
      daily RT(C) and RT(T) during MH and HG feeding (R(2) = 0.88 and 0.43,
      respectively). There was a high association between low RpH and high ruminal
      temperature, with the highest associations being between duration (min/d) of RpH
      <6.0 and duration of RT(C) >39.0 degrees C (R(2) = 0.68) and RT(T) >39.2 degrees
      C (R(2) = 0.72). Unlike the telemetric system, the conventional system requires
      cow cannulation; therefore, the current study provided a noninvasive alternative
      for measuring ruminal temperature and the prediction of RpH. Additional studies
      are needed to develop an algorithm that accounts for diet type, seasonal
      variation in temperature, and core body temperature to predict subacute ruminal
      acidosis effectively on farm.

PMID- 19841230
TI  - Genetic components of heat stress for dairy cattle with multiple lactations.
AB  - Data included 585,119 test-day records for milk, fat, and protein yields from the
      first, second, and third parities of 38,608 Holsteins in Georgia. Daily
      temperature-humidity indexes (THI) were available from public weather stations.
      Models included a repeatability test-day model with a random regression on a
      function of THI and a test-day random regression model using linear splines with
      knots at 5, 50, 200, and 305 d in milk and a function of THI. Random effects were
      additive genetic and permanent environmental in the repeatability model and
      additive genetic, permanent environmental, and herd year in the random regression
      model. Additionally, models included fixed effects for herd test day, calving
      age, milking frequency, and lactation stage. Phenotypic variance increased by 50
      to 60% from the first to second parity for all yield traits with the
      repeatability model and by 12 to 15% from the second to third parity. General
      additive genetic variance increased by 25 to 35% from the first to second parity
      for all yield traits but decreased slightly from the second to third parity for
      milk and protein yields. Genetic variance for heat tolerance doubled from the
      first to second parity and increased by 20 to 100% from the second to third
      parity. Genetic correlations among general additive effects were lowest between
      the first and second parities (0.84 to 0.88) and were highest between the second
      and third parities (0.96 to 0.98). Genetic correlations among parities for the
      effect of heat tolerance ranged from 0.56 to 0.79. Genetic correlations between
      general and heat-tolerance effects across parities and yield traits ranged from 
      0.30 to -0.50. With the random regression model, genetic variance for heat
      tolerance for milk yield was approximately one-half that of the repeatability
      model. For milk yield, the most negative genetic correlation (approximately 
      0.45) between general and heat-tolerance effects was between 50 and 200 d in milk
      for the first parity and between 200 and 305 d in milk for the second and third
      parities. The genetic variance of heat tolerance increased substantially from the
      first to third parity. Genetic estimates of heat tolerance may be inflated with
      the repeatability model because of timing of lactations to avoid peak yield
      during hot seasons.

PMID- 19841231
TI  - Overlapping chromosomal regions for fertility traits and production traits in the
      Danish Holstein population.
AB  - Before implementing selection based on quantitative trait loci (QTL) for
      fertility, it is important to determine the existence of correlated effects
      between the fertility QTL and QTL with effects on production traits. When a QTL
      is detected for a trait that is a composite of subtraits, it is of interest to
      validate which of the subtraits are affected by the QTL. Phenotypic and marker
      data were collected from 34 grandsire families from the Danish Holstein
      population. First, the trait data for "fertility treatments" were separated into
      their underlying subtraits: uterine infections, antibiotics placed in the
      placenta, and abortions. In addition, retained placenta was selected for analysis
      because it is related to uterine infections. A genome scan was performed using
      416 microsatellite markers for the fertility treatment subtraits and retained
      placenta, and an additional genome scan for milk production traits conditional on
      the QTL regions for the subtraits and retained placenta was conducted. Second, we
      selected 24 genomic regions harboring QTL for fertility traits from a previous
      study. A QTL scan for milk production traits conditional on the selected regions
      was conducted. We found that 16 selected genomic regions containing a QTL for
      fertility (including the fertility treatment subtraits and retained placenta)
      also harbored QTL for milk yield or milk composition traits. Furthermore, 12 QTL
      regions corresponding to 9 different fertility traits (including the fertility
      treatment subtraits) did not harbor a QTL for milk production or milk composition
      traits; that is, the region was specific for the fertility trait. The genome scan
      for the fertility treatment subtraits did not correspond to the QTL found for
      fertility treatments. No QTL were detected for the subtrait abortion, however
      genome scans for retained placenta revealed 4 different QTL.

PMID- 19841232
TI  - Effects of milk fat composition, DGAT1, and SCD1 on fertility traits in Dutch
      Holstein cattle.
AB  - Recently, selective breeding was proposed as a means of changing the fatty acid
      composition of milk to improve its nutritional quality. Before implementing such
      breeding objectives, effects on other economically important traits should be
      investigated. The objectives of this study were to examine 1) the effect of milk
      fat composition, and 2) the effect of polymorphisms of DGAT1 and SCD1 genes on
      female fertility in commercial Dutch Holstein-Friesian cattle. Data on 1,745
      first-lactation cows were analyzed by fitting linear mixed models. We found that
      higher concentrations of trans fatty acids within total milk fat negatively
      affected reproductive performance. Furthermore, results suggested a potential
      effect of the DGAT1 polymorphism on nonreturn rates for insemination 28 and 56 d
      after the first service. Our results can be used to assess the correlated effects
      of breeding for improved milk fat composition on reproduction, thereby allowing
      for better evaluation of breeding programs before implementation.

PMID- 19841233
TI  - Predictive abilities of different statistical models for analysis of survival
      data in dairy cattle.
AB  - The objective of this study was to compare alternative trait definitions and
      statistical models for genetic evaluation of survival in dairy cattle. Data from
      the first 5 lactations of 808,750 first-crop daughters of 3,064 Norwegian Red
      sires were analyzed. Seven sire models were used for genetic analyses: linear and
      threshold cross-sectional models for binary survival scores from first lactation;
      a linear multi-trait model for survival scores from the first 3 lactations;
      linear and threshold repeatability models for survival scores from the first 5
      lactations; a Weibull frailty model for herd life in first lactation; and a
      Weibull frailty model for herd life in the first 5 lactations. The models were
      compared to assess predictive ability of sire estimated breeding values with
      respect to average survival 365 d after first calving for second-crop daughters
      (not included in calculation of predicted transmitting abilities) of 375 elite
      sires. Generally, the linear multi-trait model analyzing survival in the first 3
      lactations as correlated traits gave more-accurate predicted sire breeding values
      compared with both linear and Weibull frailty models using data from first
      lactation only, even when the latter models were extended to include data up to
      the sixth lactation. The Weibull frailty models did not improve predictive
      ability of sire estimated breeding values over what was obtained using a simple
      cross-sectional linear model for binary survival in first lactation.

PMID- 19841234
TI  - Genetic parameters for anovulation and pregnancy loss in dairy cattle.
AB  - The objectives were to estimate heritabilities and genetic variances for
      anovulation at ~50 d in milk and pregnancy loss occurring between first and
      second pregnancy diagnoses after artificial insemination. Data were originally
      collected for trials on reproductive management. Anovulation data consisted of
      5,818 records from 13 studies in 8 herds with an overall prevalence of 23.3%. A
      Bayesian approach using Markov Chain Monte Carlo methods was used in mixed
      threshold models for both traits. The statistical model for anovulation included
      fixed effects [parity, herd-study-treatment, and body condition score (BCS)],
      covariates (inbreeding and milk yield), and random effects (sire and residual). A
      second statistical model included all terms in the first model except BCS. In
      addition, 2 bivariate, mixed sire models were used to analyze anovulation with
      BCS and anovulation with milk yield. The posterior mean heritability estimate for
      anovulation was 0.171 [posterior standard deviation (PSD) = 0.052]. Correlations
      of anovulation with milk yield were as follows: genetic = 0.168, PSD = 0.187;
      residual = -0.046, PSD = 0.022; and phenotypic = -0.036. Bivariate analysis of
      BCS with anovulation showed a genetic correlation (-0.301, PSD = 0.177) and
      phenotypic correlation (-0.192, PSD = 0.019). Pregnancy-loss data consisted of
      3,775 records from 14 studies in 8 herds with an overall prevalence of 14.4%.
      Analysis of pregnancy loss used a sire-maternal grandsire threshold model with
      embryo survival as the subject of analysis. Independent variables consisted of
      fixed effects (parity and herd-study), covariates (embryo and maternal
      inbreeding), and random effects (sire of embryo, maternal grandsire of embryo,
      and residual). In addition, separate sire models were analyzed using embryo as
      the subject and cow as the subject of analysis. The sire-maternal grandsire model
      yielded a heritability for direct effect of 0.489 (PSD = 0.221) and for maternal
      effects of 0.166 (PSD = 0.113). In this study, the breeding value variance for
      embryo effects was 3 times the breeding value variance for maternal effects,
      indicating that, at the level of breeding values, the embryo's ability to survive
      has a greater effect on pregnancy loss than does the cow's ability to maintain
      the pregnancy. These results suggest that genetic improvement of reproductive
      performance could be enhanced by selection for fundamental measures such as
      abnormally long periods of postpartum anovulation and pregnancy loss. Larger
      studies of these traits are needed to obtain parameter estimates with greater
      precision.

PMID- 19841235
TI  - Genetic and nongenetic variation in concentration of selenium, calcium,
      potassium, zinc, magnesium, and phosphorus in milk of Dutch Holstein-Friesian
      cows.
AB  - Minerals found in milk, such as Se, Ca, K, Zn, Mg, and P, contribute to several
      vital physiological processes. The aim of this study was to quantify the genetic
      variation in levels of Se, Ca, K, Zn, Mg, and P in milk and to quantify the
      between-herd variation in the levels of these minerals in milk. One morning milk
      sample from each of 1,860 Dutch Holstein-Friesian cows from 388 commercial herds
      in the Netherlands was used. Concentration of minerals was determined by
      inductively coupled plasma-atomic emission spectrometry. Variance components were
      estimated using an animal model with covariates for days in milk and age at first
      calving; fixed effects for season of calving and effect of test or proven bull;
      and random effects for animal, herd, and error. Heritability and proportion of
      phenotypic variation that can be explained by herd were estimated using
      univariate analysis. The intraherd heritability for Se was low (0.20) whereas
      herd explained 65% of the total variation in Se. Variation between herds most
      likely results from variation in Se content in the feed, which partly reflects
      variation in Se levels in the soil. Intraherd heritabilities for Ca, K, Zn, Mg,
      and P were moderate to high and were 0.57, 0.46, 0.41, 0.60, and 0.62,
      respectively. For Ca, K, Zn, Mg, and P, the proportions of phenotypic variation
      that could be explained by herd were low (0.13-0.24). This study shows that there
      are possibilities for altering the mineral composition of milk. For Ca, K, Zn,
      Mg, and P, there are good prospects for selective breeding whereas, for Se,
      measures at farm level may be more effective.

PMID- 19841236
TI  - Short communication: genetic relationships between the Holstein cow populations
      of three European dairy countries.
AB  - The degree of relatedness was studied in 3 dairy cow populations from Great
      Britain (GBR), Italy (ITA), and Ireland (IRL) by using cows born from 2003 to
      2006. Effective population size, inbreeding coefficient (F), and average
      relationship in the top and bottom 4,000 cows ranked on a profit index value
      (PIV) or milk yield evaluations were studied. Average inbreeding was
      approximately 2% in GBR and ITA, was 1% in IRL, but was slightly more than 2%
      when the joint pedigree was used. The average F for the joint population was 10
      to 15% higher than estimates averaged across the 3 populations, reflecting the
      increased completeness of pedigree information in the joint pedigree. Effective
      population size in the joint pedigree was approximately 12% lower than estimates
      within the individual countries. The average genetic relationships for the top
      4,000 PIV cows were not markedly different from those based on milk evaluation in
      GBR and ITA, but were approximately 2% lower in IRL. This was due to the use of
      an index with less weight on production traits in IRL compared with GBR and ITA.
      However, selection of the top 4,000 cows on PIV reduced the degree of relatedness
      across the 3 countries. The use of common sires accounted for most of the
      relatedness across the 3 countries, more than did the use of related sires or
      common foreign dams.

PMID- 19841237
TI  - Adaptation and failure of pancreatic beta cells in murine models with different
      degrees of metabolic syndrome.
AB  - The events that contribute to the expansion of beta-cell mass and enhanced beta
      cell function in insulin-resistant states have not been elucidated fully.
      Recently, we showed that beta-cell adaptation failed dramatically in adult,
      insulin-resistant POKO mice, which contrasts with the appropriate expansion of
      beta cells in their ob/ob littermates. Thus, we hypothesised that
      characterisation of the islets in these mouse models at an early age should
      provide a unique opportunity to: (1) identify mechanisms involved in sensing
      insulin resistance at the level of the beta cells, (2) identify molecular
      effectors that contribute to increasing beta-cell mass and function, and (3)
      distinguish primary events from secondary events that are more likely to be
      present at more advanced stages of diabetes. Our results define the POKO mouse as
      a model of early lipotoxicity. At 4 weeks of age, it manifests with inappropriate
      beta-cell function and defects in proliferation markers. Other well-recognised
      pathogenic effectors that were observed previously in 16-week-old mice, such as
      increased reactive oxygen species (ROS), macrophage infiltration and endoplasmic
      reticulum (ER) stress, are also present in both young POKO and young ob/ob mice,
      indicating the lack of predictive power with regards to the severity of beta-cell
      failure. Of interest, the relatively preserved lipidomic profile in islets from
      young POKO mice contrasted with the large changes in lipid composition and the
      differences in the chain length of triacylglycerols in the serum, liver, muscle
      and adipose tissue in adult POKO mice. Later lipotoxic insults in adult beta
      cells contribute to the failure of the POKO beta cell. Our results indicate that
      the rapid development of insulin resistance and beta-cell failure in POKO mice
      makes this model a useful tool to study early molecular events leading to insulin
      resistance and beta-cell failure. Furthermore, comparisons with ob/ob mice might
      reveal important adaptive mechanisms in beta cells with either therapeutic or
      diagnostic potential.

PMID- 19841238
TI  - Telomerase reverse transcriptase-dependent telomere equilibration mitigates
      tissue dysfunction in mTert heterozygotes.
AB  - Autosomal dominant mutations in telomere-associated factors elicit a disease
      known as dyskeratosis congenita (DKC), and patients suffer proliferative
      abnormalities associated with telomere erosion. Mice that are heterozygous for
      telomerase genes (Tert or Terc, hereafter referred to as mTert and mTerc) are
      useful models of telomerase haploinsufficiency, but do not strictly mimic DKC. In
      strains with long telomeres (>60 kbp), animals that are heterozygous for mTert
      undergo telomere erosion for nine generations and remain phenotypically normal.
      In an mTerc heterozygous strain with short telomeres (<15 kbp), early mortality
      arises after five to six generations, but dyskeratosis occurs only upon the
      further loss of mPot1b. We show that prolonged mTert heterozygosity (for greater
      than ten generations) did not elicit disease, even upon heterozygote
      interbreeding, and that telomeres reset to wild-type lengths. This lengthening
      did not occur in nullizygotes, and short telomeres inherited from mTert null
      parents were rescued only in heterozygous progeny. In the bone marrow,
      nullizygotes remained competent for radioprotection for three generations. Thus,
      gradual telomere erosion in the presence of telomerase may enable subsequent
      telomere extension, similar to that described in budding yeast. We speculate
      whether such adaptation occurs in normal human cells (or whether it could be
      induced in DKC-derived cells), and whether it might mitigate the impact of
      telomerase inhibition upon stem cells during cancer therapy.

PMID- 19841239
TI  - Telomeres and Tetrahymena: an interview with Elizabeth Blackburn.

PMID- 19841240
TI  - A conditional mouse model for human MUC1-positive endometriosis shows the
      presence of anti-MUC1 antibodies and Foxp3+ regulatory T cells.
AB  - Endometriosis is defined by the presence of tissue implants resembling
      endometrial glands outside of the uterus, at ectopic sites, frequently on the
      ovarian surface. The ectopic lesions are often invasive, resistant to therapy,
      and may predispose to endometrioid and clear cell ovarian tumors. The complex
      mechanisms leading to chronic endometriosis are mediated partly by impaired
      immune surveillance in the host. Although innate immunity has been addressed
      previously, the response of adaptive immune effectors to specific antigens has
      not been characterized, mostly because very few endometriosis antigens have been
      defined to date. We postulated that the mucin 1 (MUC1) glycoprotein, which is
      normally present on eutopic human endometrial glands and overexpressed in
      endometrioid and clear cell ovarian tumors, is also present in ectopic lesions of
      ovarian endometriosis. Furthermore, changes in MUC1 expression in endometriosis
      could promote adaptive anti-MUC1 immunity that might play a role in the malignant
      progression. To test our hypothesis, we crossed MUC1 transgenic mice, which
      express human MUC1 under the endogenous promoter, with the loxP-Stop-loxP
      Kras(G12D/+) (Kras) mice, in which endometriosis can be induced through Cre-loxP
      recombination. The double transgenic MUC1Kras mice develop benign, MUC1-positive
      ovarian lesions, closely resembling human endometriosis. Subsequent to disease
      induction, the mice generate high titers of IgM and IgG antibodies that are
      specific for MUC1. Antibodies appear early in disease and the predominance of the
      IgG1 subclass suggests Th2-driven immunity. Immune phenotyping revealed an
      accumulation of Foxp3+ CD4 regulatory T cells (Tregs) in the draining lymph nodes
      at late-stage disease. Furthermore, our observations in human endometriosis
      showed a similar recruitment of FOXP3+ CD4 T cells. Overall, our results reveal a
      Th2/Treg-dominant natural immunity in endometriosis with potential implications
      for cancer progression.

PMID- 19841241
TI  - Healthcare reform and the economy.

PMID- 19841242
TI  - Evidence-based nutrition support: Is a recession a good thing?

PMID- 19841243
TI  - Issues in complementary and alternative nutrition treatments.

PMID- 19841244
TI  - An overview of CAM: components and clinical uses.
AB  - Complementary and alternative medicine (CAM), more recently known as integrative
      health or integrative medicine, is a diverse field comprising numerous treatments
      and practitioners of various levels of training. This review defines several of
      the main CAM modalities and reviews some of the research relevant to their
      clinical application. The goal is to provide healthcare providers with a basic
      understanding of CAM to start the incorporation of proven treatments into their
      clinical practice as well as guide them to working with CAM providers;
      ultimately, such knowledge is a fundamental part of a collaborative approach to
      optimal patient health and wellness.

PMID- 19841245
TI  - The metabolic syndrome: definition, global impact, and pathophysiology.
AB  - The metabolic syndrome (MS) is a cluster of metabolic derangements that are
      associated with primary disturbances in adipose tissue. Abnormal visceral fat
      accumulates from physical inactivity and excess calories in genetically
      susceptible individuals. This increased adipocyte mass acts as an endocrine organ
      and communicates with other organ systems via increases in inflammatory
      cytokines. The resulting disorders define MS as increased waist circumference,
      decreased serum high-density lipoprotein, and increased serum triglyceride
      levels, hypertension, and insulin resistance. MS accounts for the majority of
      cardiovascular disease risk in the U.S. population. Dietary interventions, such
      as the Mediterranean diet, have been shown to improve these metabolic
      derangements. Many substances found in these diets are being investigated as
      specific therapies for MS, and when scientific substantiation is lacking, they
      may be considered as part of complementary and alternative medicine (CAM).
      However, as scientific evidence accumulates, these CAM treatments may become part
      of conventional medicine. This review will scrutinize the emerging evidence
      behind many, though not all, CAM treatments currently thought to target the
      various derangements found in MS.

PMID- 19841246
TI  - Pediatric asthma: an integrative approach to care.
AB  - Asthma in children and young adults is a complex disease with many different
      phenotypic expressions. Diagnosis is often made based on history and lung
      function including measuring airway reversibility. However, in children younger
      than 6 years of age, the diagnosis is more difficult because many children wheeze
      in the first 4-6 years of life, especially with viral infections. For those
      children, asthma treatment is often started empirically. Those who go on to
      develop chronic asthma most likely have a genetic predisposition and exposure to
      various environmental factors resulting in chronic inflammation of the lower
      respiratory tract. There are established national guidelines for diagnosing and
      treating asthma in children and adults. For persistent asthma, it is recommended
      that medications be taken on a regular basis after identifying and avoiding
      environmental triggers. Because many factors play a role in developing asthma in
      children, many nonmedical approaches to asthma and asthma-like conditions have
      been promoted even when the diagnosis is at times uncertain. The nonmedical
      approaches and therapies are often referred to as complementary and alternative
      medicine (CAM). This review will discuss the conventional therapies recommended
      for children with asthma in addition to CAM therapies, some of which have
      supporting scientific evidence. Integrating conventional and CAM therapies can
      prove to be an effective way to treat pediatric asthma, a common and chronic
      childhood lung disorder. A case is provided to illustrate how such an integrative
      approach was used in the successful treatment of a child with moderate persistent
      asthma.

PMID- 19841247
TI  - Complementary and alternative medications for women's health issues.
AB  - Women often seek alternative treatment options such as herbs, dietary
      supplements, and vitamins and minerals to treat women's health issues across the
      lifespan. Women may use complementary and alternative supplements for
      dysmenorrhea, premenstrual syndrome, infertility, nausea and vomiting during
      pregnancy, and symptoms of menopause. In general, there is a deficit of well
      designed, randomized, controlled trials to evaluate the efficacy and safety of
      complementary and alternative medicine for these indications, which makes it
      difficult to provide evidence-based recommendations. This review outlines the
      evidence for efficacy and safety that is currently available for dietary
      supplement use by women to manage health conditions specific to the female
      patient.

PMID- 19841248
TI  - CAM and respiratory disease.
AB  - Complementary and alternative medicine is used commonly for respiratory diseases.
      This review summarizes data that identify potential links between dietary intake
      and asthma, and results of interventional trials of herbal substances for the
      treatment of asthma, chronic obstructive pulmonary disease, and acute bronchitis.

PMID- 19841249
TI  - Formulation, stability, and administration of parenteral nutrition with new lipid
      emulsions.
AB  - Intravenous lipid emulsions (IVLE) are an important source of energy and
      essential fatty acids and their incorporation into pediatric and adult parenteral
      nutrition (PN) regimens has revolutionized nutrition therapy. However, their
      clinical use has not been without risk, and will continue to remain so because of
      the intravenous route of administration. Pharmaceutical and microbiological
      concerns are centered around the methods of compounding all-in-one (AIO)
      admixtures, but these can be largely minimized with today's technologies and
      advanced understanding of aseptic principles. Modern lipid products, based on
      olive, coconut, and/or fish oils, have demonstrable formulation and clinical
      benefits over traditional soybean and safflower IVLE and, when combined in the
      new multi-chamber bags, can also offer improvements in stability and safety. This
      review outlines the rationale for different lipid formulations in PN admixtures,
      reviews the factors influencing stability and efficacy of lipid-based AIO
      regimens and evaluates some technologies for minimizing peroxidation and
      maximizing stability of AIO admixtures.

PMID- 19841250
TI  - Enteral nutrition in nursing home residents: a 5-year (2001-2005) epidemiological
      analysis.
AB  - BACKGROUND: Despite controversy and increasing use of enteral nutrition (EN)
      among elderly people, descriptive population-based data are scarce. The aim of
      this study was to evaluate the epidemiological data of nursing home residents
      (NHRs) who received EN in a northeast area of Italy. METHODS: All NHRs referred
      to our Nutrition Service for EN between 2001 and 2005 were enrolled. Data
      collected at EN initiation included age, gender, underlying disease, Karnofsky
      index, type of enteral access device, presence of pressure ulcers, weight, body
      mass index, and daily enteral intake. The outcomes considered were patient
      survival and duration of therapy. RESULTS: The 482 NHRs (130 males; 352 females)
      received EN. The mean incidence (cases/million population/year) and prevalence
      (cases/million population) were 223.4 and 279.4, respectively. An average of 6.6%
      of all NHRs were tube fed. EN was prescribed for the following conditions: 27.7%
      cerebrovascular accident, 54.6% neurodegenerative disease, 2.7% head and neck
      cancer, 1.2% abdominal cancer, 1.3% head trauma, 4.8% congenital disease, 7.7%
      other. Almost all patients had a Karnofsky index <or=50; 42.3% of patients had
      pressure ulcers. The median duration of EN was 296 days and the median overall
      survival was 411 days. CONCLUSIONS: NHRs receiving EN were mainly afflicted with
      neurodegenerative and cerebrovascular diseases, functional impairments, and a
      high incidence of pressure sores. The mortality rate was low compared with others
      reported in literature. The low EN use among NHRs in our study may suggest a
      limited use in advanced dementia and at end-stage of life.

PMID- 19841251
TI  - Vitamin D: a D-lightful health supplement.

PMID- 19841252
TI  - A commentary on the construction of weight velocity charts.

PMID- 19841253
TI  - Development of a Medicaid behavioral health case-mix model.
AB  - Many Medicaid programs have either fully or partially carved out mental health
      services. The evaluation of carved out plans requires a case-mix model that
      accounts for differing health status across Medicaid managed care plans. This
      article develops a diagnosis-based case-mix adjustment system specific to
      Medicaid behavioral health care. Several different model specifications are
      compared that use untransformed, square root transformed, and log-transformed
      expenditures.

PMID- 19841254
TI  - Experimental determination of the evolvability of a transcription factor.
AB  - Sequence-specific binding of a transcription factor to DNA is the central event
      in any transcriptional regulatory network. However, relatively little is known
      about the evolutionary plasticity of transcription factors. For example, the
      exact functional consequence of an amino acid substitution on the DNA-binding
      specificity of most transcription factors is currently not predictable.
      Furthermore, although the major structural families of transcription factors have
      been identified, the detailed DNA-binding repertoires within most families have
      not been characterized. We studied the sequence recognition code and evolvability
      of the basic helix-loop-helix transcription factor family by creating all
      possible 95 single-point mutations of five DNA-contacting residues of Max, a
      human helix-loop-helix transcription factor and measured the detailed DNA-binding
      repertoire of each mutant. Our results show that the sequence-specific repertoire
      of Max accessible through single-point mutations is extremely limited, and we are
      able to predict 92% of the naturally occurring diversity at these positions. All
      naturally occurring basic regions were also found to be accessible through
      functional intermediates. Finally, we observed a set of amino acids that are
      functional in vitro but are not found to be used naturally, indicating that
      functionality alone is not sufficient for selection.

PMID- 19841255
TI  - Zyklophin, a systemically active selective kappa opioid receptor peptide
      antagonist with short duration of action.
AB  - The cyclic peptide zyklophin {[N-benzylTyr(1),cyclo(D-Asp(5),Dap(8))-dynorphin A
      (1-11)NH(2), Patkar KA, et al. (2005) J Med Chem 48: 4500-4503} is a selective
      peptide kappa opioid receptor (KOR) antagonist that shows activity following
      systemic administration. Systemic (1-3 mg/kg s.c.) as well as central (0.3-3 nmol
      intracerebroventricular, i.c.v.) administration of this peptide dose-dependently
      antagonizes the antinociception induced by the selective KOR agonist U50,488 in
      C57BL/6J mice tested in the 55 degrees C warm water tail withdrawal assay.
      Zyklophin administration had no effect on morphine- or SNC-80-mediated
      antinociception, suggesting that zyklophin selectively antagonizes KOR in vivo.
      Additionally, the antagonism of antinociception induced by centrally (i.c.v.)
      administered U50,488 following peripheral administration of zyklophin strongly
      suggests that the peptide crosses the blood-brain barrier to antagonize KOR in
      the CNS. Most importantly, the antagonist activity of zyklophin (3 mg/kg s.c.)
      lasts less than 12 h, which contrasts sharply with the exceptionally long
      duration of antagonism reported for the established small-molecule selective KOR
      antagonists such as nor-binaltorphimine (nor-BNI) that last weeks after a single
      administration. Systemically administered zyklophin (3 mg/kg s.c.) also prevented
      stress-induced reinstatement of cocaine-seeking behavior in a conditioned place
      preference assay. In conclusion, the peptide zyklophin is a KOR-selective
      antagonist that exhibits the desired shorter duration of action, and represents a
      significant advance in the development of KOR-selective antagonists.

PMID- 19841256
TI  - Endogenous nitric oxide regulates the recovery of the radiation-resistant
      bacterium Deinococcus radiodurans from exposure to UV light.
AB  - Deinococcus radiodurans (Dr) withstands desiccation, reactive oxygen species, and
      doses of radiation that would be lethal to most organisms. Deletion of a gene
      encoding a homolog of mammalian nitric oxide synthase (NOS) severely compromises
      the recovery of Dr from ultraviolet (UV) radiation damage. The Deltanos defect
      can be complemented with recombinant NOS, rescued by exogenous nitric oxide (NO)
      and mimicked in the wild-type strain with an NO scavenging compound. UV radiation
      induces both upregulation of the nos gene and cellular NO production on similar
      time scales. Growth recovery does not depend on NO being present during UV
      irradiation, but rather can be manifested by NO addition hours after exposure.
      Surprisingly, nos deletion does not increase sensitivity to oxidative damage, and
      hydrogen peroxide does not induce nos expression. However, NOS-derived NO
      upregulates transcription of obgE, a gene involved in bacterial growth
      proliferation and stress response. Overexpression of the ObgE GTPase in the
      Deltanos background substantially alleviates the growth defect after radiation
      damage. Thus, NO acts as a signal for the transcriptional regulation of growth in
      D. radiodurans.

PMID- 19841257
TI  - Phylogenetic and trait similarity to a native species predict herbivory on non
      native oaks.
AB  - Introduced plants tend to experience less herbivory than natives, although
      herbivore loads vary widely. Herbivores may switch hosts onto an introduced plant
      for at least two reasons. They may recognize the novel plant as a potential host
      based on similarity of the plant's traits to the traits of one of its native
      hosts, a similarity that may or may not exhibit phylogenetic signal.
      Alternatively, herbivores may feed optimally, assessing which introduced plants
      provide the best nutrition irrespective of similarity to native species. Here, we
      created a phylogeny of 57 oak (Quercus) taxa, which were grown outside of their
      ranges in a common botanical garden that contained one abundant native oak
      (Quercus lobata). We used the phylogeny to estimate the phylogenetic conservatism
      of herbivory by two feeding guilds of insects (leaf chewers and leaf miners) and
      11 plant traits expected to affect herbivore performance. We found high
      phylogenetic signal in chewing damage but not mining damage and all traits except
      for leaf maturation time. Introduced oaks that are more closely related to the
      native oak received more chewing and mining damage than distantly related oaks,
      and introduced oaks that had greater overall similarity in leaf traits also
      received higher chewing damage but not mining damage. These results demonstrate
      that interactions between introduced plants and their herbivores are driven
      independently by traits that track plant phylogeny and leaf traits that likely
      affect herbivore performance.

PMID- 19841258
TI  - Unraveling the structure of DNA during overstretching by using multicolor, single
      molecule fluorescence imaging.
AB  - Single-molecule manipulation studies have revealed that double-stranded DNA
      undergoes a structural transition when subjected to tension. At forces that
      depend on the attachment geometry of the DNA (65 pN or 110 pN), it elongates
      approximately 1.7-fold and its elastic properties change dramatically. The nature
      of this overstretched DNA has been under debate. In one model, the DNA
      cooperatively unwinds, while base pairing remains intact. In a competing model,
      the hydrogen bonds between base pairs break and two single DNA strands are
      formed, comparable to thermal DNA melting. Here, we resolve the structural basis
      of DNA overstretching using a combination of fluorescence microscopy, optical
      tweezers, and microfluidics. In DNA molecules undergoing the transition, we
      visualize double- and single-stranded segments using specific fluorescent labels.
      Our data directly demonstrate that overstretching comprises a gradual conversion
      from double-stranded to single-stranded DNA, irrespective of the attachment
      geometry. We found that these conversions favorably initiate from nicks or free
      DNA ends. These discontinuities in the phosphodiester backbone serve as
      energetically favorable nucleation points for melting. When both DNA strands are
      intact and no nicks or free ends are present, the overstretching force increases
      from 65 to 110 pN and melting initiates throughout the molecule, comparable to
      thermal melting. These results provide unique insights in the thermodynamics of
      DNA and DNA-protein interactions.

PMID- 19841259
TI  - Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic
      axis formation.
AB  - Members of the Wnt family are secreted glycoproteins that trigger cellular
      signals essential for proper development of organisms. Cellular signaling induced
      by Wnt proteins is involved in diverse developmental processes and human
      diseases. Previous studies have generated an enormous wealth of knowledge on the
      events in signal-receiving cells. However, relatively little is known about the
      making of Wnt in signal-producing cells. Here, we describe that Gpr177, the mouse
      orthologue of Drosophila Wls, is expressed during formation of embryonic axes.
      Embryos with deficient Gpr177 exhibit defects in establishment of the body axis,
      a phenotype highly reminiscent to the loss of Wnt3. Although many different
      mammalian Wnt proteins are required for a wide range of developmental processes,
      the Wnt3 ablation exhibits the earliest developmental abnormality. This suggests
      that the Gpr177-mediated Wnt production cannot be substituted. As a direct target
      of Wnt, Gpr177 is activated by beta-catenin and LEF/TCF-dependent transcription.
      This activation alters the cellular distributions of Gpr177 which binds to Wnt
      proteins and assists their sorting and secretion in a feedback regulatory
      mechanism. Our findings demonstrate that the loss of Gpr177 affects Wnt
      production in the signal-producing cells, leading to alterations of Wnt signaling
      in the signal-receiving cells. A reciprocal regulation of Wnt and Gpr177 is
      essential for the patterning of the anterior-posterior axis during mammalian
      development.

PMID- 19841260
TI  - An essential role for RPE-derived soluble VEGF in the maintenance of the
      choriocapillaris.
AB  - Clinical and experimental observations indicate a role for VEGF secreted by the
      retinal pigment epithelium (RPE) in the maintenance of the choriocapillaris (CC).
      VEGF in mice is produced as three isoforms, VEGF120, VEGF164, and VEGF188, that
      differ in their ability to bind heparan sulfate proteoglycan. RPE normally
      produces the more soluble isoforms, VEGF120 and VEGF164, but virtually no
      VEGF188, reflecting the fact that molecules secreted by the RPE must diffuse
      across Bruch's membrane (BrM) to reach the choriocapillaris. To determine the
      role of RPE-derived soluble VEGF on the choriocapillaris survival, we used mice
      that produce only VEGF188. VEGF188/188 mice exhibited normal choriocapillaris
      development. However, beginning at 7 months of age, we observed a progressive
      degeneration characterized by choriocapillaris atrophy, RPE and BrM
      abnormalities, culminating in areas of RPE loss and dramatic choroidal
      remodeling. Increased photoreceptor apoptosis in aged VEGF188/188 mice led to a
      decline in visual acuity as detected by electroretinogram (ERG). These changes
      are reminiscent of geographic atrophy (GA) and point to a role for RPE-derived
      VEGF in the maintenance of the choriocapillaris.

PMID- 19841261
TI  - Direct observation of ultrafast folding and denatured state dynamics in single
      protein molecules.
AB  - Single-molecule fluorescence resonance energy transfer (smFRET) experiments are
      extremely useful in studying protein folding but are generally limited to time
      scales of greater than approximately 100 micros and distances greater than
      approximately 2 nm. We used single-molecule fluorescence quenching by
      photoinduced electron transfer, detecting short-range events, in combination with
      fluorescence correlation spectroscopy (PET-FCS) to investigate folding dynamics
      of the small binding domain BBL with nanosecond time resolution. The kinetics of
      folding appeared as a 10-micros decay in the autocorrelation function, resulting
      from stochastic fluctuations between denatured and native conformations of
      individual molecules. The observed rate constants were probe independent and in
      excellent agreement with values derived from conventional temperature-jump (T
      jump) measurements. A submicrosecond relaxation was detected in PET-FCS data that
      reported on the kinetics of intrachain contact formation within the thermally
      denatured state. We engineered a mutant of BBL that was denatured under the
      reaction conditions that favored folding of the parent wild type ("D(phys)").
      D(phys) had the same kinetic signature as the thermally denatured state and
      revealed segmental diffusion with a time constant of intrachain contact formation
      of 500 ns. This time constant was more than 10 times faster than folding and in
      the range estimated to be the "speed limit" of folding. D(phys) exhibited
      significant deviations from a random coil. The solvent viscosity and temperature
      dependence of intrachain diffusion showed that chain motions were slaved by the
      presence of intramolecular interactions. PET-FCS in combination with protein
      engineering is a powerful approach to study the early events and mechanism of
      ultrafast protein folding.

PMID- 19841262
TI  - Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the
      breast and head and neck.
AB  - The transcription factor gene MYB was identified recently as an oncogene that is
      rearranged/duplicated in some human leukemias. Here we describe a new mechanism
      of activation of MYB in human cancer involving gene fusion. We show that the
      t(6;9)(q22-23;p23-24) translocation in adenoid cystic carcinomas (ACC) of the
      breast and head and neck consistently results in fusions encoding chimeric
      transcripts predominantly consisting of MYB exon 14 linked to the last coding
      exon(s) of NFIB. The minimal common part of MYB deleted as the result of fusion
      was exon 15 including the 3'-UTR, which contains several highly conserved target
      sites for miR-15a/16 and miR-150 microRNAs. These microRNAs recently were shown
      to regulate MYB expression negatively. We suggest that deletion of these target
      sites may disrupt repression of MYB leading to overexpression of MYB-NFIB
      transcripts and protein and to activation of critical MYB targets, including
      genes associated with apoptosis, cell cycle control, cell growth/angiogenesis,
      and cell adhesion. Forced overexpression of miR-15a/16 and miR-150 in primary
      fusion-positive ACC cells did not significantly alter the expression of MYB as
      compared with leukemic cells with MYB activation/duplication. Our data indicate
      that the MYB-NFIB fusion is a hallmark of ACC and that deregulation of the
      expression of MYB and its target genes is a key oncogenic event in the
      pathogenesis of ACC. Our findings also suggest that the gain-of-function activity
      resulting from the MYB-NFIB fusion is a candidate therapeutic target.

PMID- 19841263
TI  - Peripatetic health-care workers as potential superspreaders.
AB  - Many nosocomial outbreaks exhibit "superspreading events" in which cross
      transmission occurs via a single individual to a large number of patients. We
      investigated how heterogeneity in Health-Care Worker (HCW) behaviors, especially
      compliance to hand hygiene, may cause superspreading events. In particular, we
      compared the superspreading potential of peripatetic (noncohorted) HCWs with that
      of other HCWs. We developed an agent-based model for hand transmission of a
      pathogen in a hospital ward. Three HCW profiles were allowed: 2 assigned
      profiles, one with frequent contacts with a limited number of patients, another
      with fewer contacts but with more patients; and one peripatetic profile, with a
      single daily contact with all patients. We used data from the literature on
      common nosocomial pathogens (Staphylococcus aureus, Enterococci). The average
      number of patients colonized over 1 month increases with noncompliance to hand
      hygiene. Importantly, we show that this increase depends on the profile of
      noncompliant HCWs; for instance, it remains low for a single noncompliant
      assigned HCW but can be quite large for a single noncompliant peripatetic HCW.
      Outbreaks with this single fully noncompliant peripatetic HCW (representing only
      4.5% of the staff) are similar to those predicted when all HCWs are noncompliant
      following 23% of patient contacts. Noncompliant peripatetic HCWs may play a
      disproportionate role in disseminating pathogens in a hospital ward. Their unique
      profile makes them potential superspreaders. This suggests that average
      compliance to hygiene may not be a good indicator of nosocomial risk in real life
      health care settings with several HCW profiles.

PMID- 19841265
TI  - Recent changes in a remote Arctic lake are unique within the past 200,000 years.
AB  - The Arctic is currently undergoing dramatic environmental transformations, but it
      remains largely unknown how these changes compare with long-term natural
      variability. Here we present a lake sediment sequence from the Canadian Arctic
      that records warm periods of the past 200,000 years, including the 20th century.
      This record provides a perspective on recent changes in the Arctic and predates
      by approximately 80,000 years the oldest stratigraphically intact ice core
      recovered from the Greenland Ice Sheet. The early Holocene and the warmest part
      of the Last Interglacial (Marine Isotope Stage or MIS 5e) were the only periods
      of the past 200,000 years with summer temperatures comparable to or exceeding
      today's at this site. Paleoecological and geochemical data indicate that the past
      three interglacial periods were characterized by similar trajectories in
      temperature, lake biology, and lakewater pH, all of which tracked orbitally
      driven solar insolation. In recent decades, however, the study site has deviated
      from this recurring natural pattern and has entered an environmental regime that
      is unique within the past 200 millennia.

PMID- 19841264
TI  - Atomic substitution reveals the structural basis for substrate adenine
      recognition and removal by adenine DNA glycosylase.
AB  - Adenine DNA glycosylase catalyzes the glycolytic removal of adenine from the
      promutagenic A.oxoG base pair in DNA. The general features of DNA recognition by
      an adenine DNA glycosylase, Bacillus stearothermophilus MutY, have previously
      been revealed via the X-ray structure of a catalytically inactive mutant protein
      bound to an A:oxoG-containing DNA duplex. Although the structure revealed the
      substrate adenine to be, as expected, extruded from the DNA helix and inserted
      into an extrahelical active site pocket on the enzyme, the substrate adenine
      engaged in no direct contacts with active site residues. This feature was
      paradoxical, because other glycosylases have been observed to engage their
      substrates primarily through direct contacts. The lack of direct contacts in the
      case of MutY suggested that either MutY uses a distinctive logic for substrate
      recognition or that the X-ray structure had captured a noncatalytically competent
      state in lesion recognition. To gain further insight into this issue, we
      crystallized wild-type MutY bound to DNA containing a catalytically inactive
      analog of 2'-deoxyadenosine in which a single 2'-H atom was replaced by fluorine.
      The structure of this fluorinated lesion-recognition complex (FLRC) reveals the
      substrate adenine buried more deeply into the active site pocket than in the
      prior structure and now engaged in multiple direct hydrogen bonding and
      hydrophobic interactions. This structure appears to capture the catalytically
      competent state of adenine DNA glycosylases, and it suggests a catalytic
      mechanism for this class of enzymes, one in which general acid-catalyzed
      protonation of the nucleobase promotes glycosidic bond cleavage.

PMID- 19841266
TI  - F1-dependent translation of mitochondrially encoded Atp6p and Atp8p subunits of
      yeast ATP synthase.
AB  - The ATP synthase of yeast mitochondria is composed of 17 different subunit
      polypeptides. We have screened a panel of ATP synthase mutants for impaired
      expression of Atp6p, Atp8p, and Atp9p, the only mitochondrially encoded subunits
      of ATP synthase. Our results show that translation of Atp6p and Atp8p is
      activated by F(1) ATPase (or assembly intermediates thereof). Mutants lacking the
      alpha or beta subunits of F(1), or the Atp11p and Atp12p chaperones that promote
      F(1) assembly, have normal levels of the bicistronic ATP8/ATP6 mRNAs but fail to
      synthesize Atp6p and Atp8p. F(1) mutants are also unable to express ARG8(m) when
      this normally nuclear gene is substituted for ATP6 or ATP8 in mitochondrial DNA.
      Translational activation by F(1) is also supported by the ability of ATP22, an
      Atp6p-specific translation factor, to restore Atp6p and to a lesser degree Atp8p
      synthesis in the absence of F(1). These results establish a mechanism by which
      expression of ATP6 and ATP8 is translationally regulated by F(1) to achieve a
      balanced output of two compartmentally separated sets of ATP synthase genes.

PMID- 19841267
TI  - Age at first reproduction explains rate variation in the strepsirrhine molecular
      clock.
AB  - Although the molecular clock hypothesis posits that the rate of molecular change
      is constant over time, there is evidence that rates vary among lineages. Some of
      the strongest evidence for variable molecular rates comes from the primates;
      e.g., the "hominoid slowdown." These rate differences are hypothesized to
      correlate with certain species attributes, such as generation time and body size.
      Here, we examine rates of molecular change in the strepsirrhine suborder of
      primates and test whether body size or age at first reproduction (a proxy for
      generation time) explains patterns of rate variation better than a null model
      where the molecular clock is independent of these factors. To examine these
      models, we analyzed DNA sequences from four pairs of recently diverged
      strepsirrhine sister taxa to estimate molecular rates by using sign tests,
      likelihood ratio tests, and regression analyses. Our analysis does not support a
      model where body weight or age at first reproduction strongly influences rates of
      molecular evolution across mitochondrial and nuclear sites. Instead, our analysis
      supports a model where age at first reproduction influences neutral evolution in
      the nuclear genome. This study supports the generation time hypothesis for rate
      variation in the nuclear molecular clock. Molecular clock variation due to
      generation time may help to resolve the discordance between molecular and
      paleontological estimates for divergence date estimates in primate evolution.

PMID- 19841268
TI  - Interaction of malaria with a common form of severe thalassemia in an Asian
      population.
AB  - In many Asian populations, the commonest form of severe thalassemia results from
      the coinheritance of HbE and beta thalassemia. The management of this disease is
      particularly difficult because of its extreme clinical diversity; although some
      genetic and adaptive factors have been identified as phenotypic modifiers, the
      reasons remain unclear. Because the role of the environment in the course of
      severe thalassemia has been neglected completely and because malaria due to both
      Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we
      carried out a pilot study of patients with HbE beta thalassemia that showed high
      frequencies of antibodies to both parasite species and that 28.6% of the children
      had DNA-based evidence of current infection with P. vivax. Malarial antibodies
      then were assessed in patients with HbE beta thalassemia compared with those in
      age-matched controls. There was a significant increase in the frequency of
      antibodies in the thalassemic patients, particularly against P. vivax and in
      young children. There was also a higher frequency in those who had been
      splenectomized compared with those with intact spleens, although in the latter it
      was still higher than that in the controls. The thalassemic patients showed
      significant correlations between malaria antibody status and phenotype. Patients
      with HbE beta thalassemia may be more prone to malaria, particularly P. vivax,
      which is reflected in their clinical severity. Because P. vivax malaria is
      widespread in Asia, further studies of its interaction with HbE beta thalassemia
      and related diseases are required urgently as a part of ongoing thalassemia
      control programs.

PMID- 19841269
TI  - Nitrogen management is essential to prevent tropical oil palm plantations from
      causing ground-level ozone pollution.
AB  - More than half the world's rainforest has been lost to agriculture since the
      Industrial Revolution. Among the most widespread tropical crops is oil palm
      (Elaeis guineensis): global production now exceeds 35 million tonnes per year. In
      Malaysia, for example, 13% of land area is now oil palm plantation, compared with
      1% in 1974. There are enormous pressures to increase palm oil production for
      food, domestic products, and, especially, biofuels. Greater use of palm oil for
      biofuel production is predicated on the assumption that palm oil is an
      "environmentally friendly" fuel feedstock. Here we show, using measurements and
      models, that oil palm plantations in Malaysia directly emit more oxides of
      nitrogen and volatile organic compounds than rainforest. These compounds lead to
      the production of ground-level ozone (O(3)), an air pollutant that damages human
      health, plants, and materials, reduces crop productivity, and has effects on the
      Earth's climate. Our measurements show that, at present, O(3) concentrations do
      not differ significantly over rainforest and adjacent oil palm plantation
      landscapes. However, our model calculations predict that if concentrations of
      oxides of nitrogen in Borneo are allowed to reach those currently seen over rural
      North America and Europe, ground-level O(3) concentrations will reach 100 parts
      per billion (10(9)) volume (ppbv) and exceed levels known to be harmful to human
      health. Our study provides an early warning of the urgent need to develop
      policies that manage nitrogen emissions if the detrimental effects of palm oil
      production on air quality and climate are to be avoided.

PMID- 19841270
TI  - Long-lived states to sustain hyperpolarized magnetization.
AB  - Major breakthroughs have recently been reported that can help overcome two
      inherent drawbacks of NMR: the lack of sensitivity and the limited memory of
      longitudinal magnetization. Dynamic nuclear polarization (DNP) couples nuclear
      spins to the large reservoir of electrons, thus making it possible to detect
      dilute endogenous substances in magnetic resonance spectroscopy (MRS) and
      magnetic resonance imaging (MRI). We have designed a method to preserve enhanced
      ("hyperpolarized") magnetization by conversion into long-lived states (LLS). It
      is shown that these enhanced long-lived states can be generated for proton spins,
      which afford sensitive detection. Even in complex molecules such as peptides,
      long-lived proton states can be sustained effectively over time intervals on the
      order of tens of seconds, thus allowing hyperpolarized substrates to reach target
      areas and affording access to slow metabolic pathways. The natural abundance
      carbon-13 polarization has been enhanced ex situ by almost four orders of
      magnitude in the dipeptide Ala-Gly. The sample was transferred by the dissolution
      process to a high-resolution magnet where the carbon-13 polarization was
      converted into a long-lived state associated with a pair of protons. In Ala-Gly,
      the lifetime T(LLS) associated with the two nonequivalent H(alpha) glycine
      protons, sustained by suitable radio-frequency irradiation, was found to be seven
      times longer than their spin-lattice relaxation time constant (T(LLS)/T(1) = 7).
      At desired intervals, small fractions of the populations of long-lived states
      were converted into observable magnetization. This opens the way to observing
      slow chemical reactions and slow transport phenomena such as diffusion by
      enhanced magnetic resonance.

PMID- 19841271
TI  - Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin
      sensitization.
AB  - Cellular and tissue defects associated with insulin resistance are coincident
      with transcriptional abnormalities and are improved after insulin sensitization
      with thiazolidinedione (TZD) PPARgamma ligands. We characterized 72 human
      subjects by relating their clinical phenotypes with functional pathway
      alterations. We transcriptionally profiled 364 biopsies harvested before and
      after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month
      TZD treatment. We have identified molecular and functional characteristics of
      insulin resistant subjects and distinctions between TZD treatment responder and
      nonresponder subjects. Insulin resistant subjects exhibited alterations in
      skeletal muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose
      tissue (e.g., mitochondrial metabolism and inflammation) that improved relative
      to TZD-induced insulin sensitization. Pre-TZD treatment expression of MLXIP in
      muscle and HLA-DRB1 in adipose tissue from insulin resistant subjects was
      linearly predictive of post-TZD insulin sensitization. We have uniquely
      characterized coordinated cellular and tissue functional pathways that are
      characteristic of insulin resistance, TZD-induced insulin sensitization, and
      potential TZD responsiveness.

PMID- 19841272
TI  - Water- and nutrient-dependent effects of dietary restriction on Drosophila
      lifespan.
AB  - Dietary restriction (DR) is a widely conserved intervention leading to lifespan
      extension. Despite considerable effort, the mechanisms underlying DR remain
      poorly understood. In particular, it remains unclear whether DR prolongs life
      through conserved mechanisms in different species. Here, we show that, in the
      most common experimental conditions, lifespan extension by DR is abolished by
      providing Drosophila with ad libitum water, without altering food intake,
      indicating that DR, as conventionally studied in flies, is fundamentally
      different from the phenomenon studied in mammals. We characterize an alternative
      dietary paradigm that elicits robust lifespan extension irrespective of water
      availability, and thus likely represents a more relevant model for mammalian DR.
      Our results support the view that protein:carbohydrate ratio is the main dietary
      determinant of fly lifespan. These findings have broad implications for the study
      of lifespan and nutrition.

PMID- 19841273
TI  - Nanoparticle-based bio-barcode assay redefines "undetectable" PSA and biochemical
      recurrence after radical prostatectomy.
AB  - We report the development of a previously undescribed gold nanoparticle bio
      barcode assay probe for the detection of prostate specific antigen (PSA) at 330
      fg/mL, automation of the assay, and the results of a clinical pilot study
      designed to assess the ability of the assay to detect PSA in the serum of 18 men
      who have undergone radical prostatectomy for prostate cancer. Due to a lack of
      sensitivity, available PSA immunoassays are often not capable of detecting PSA in
      the serum of men after radical prostatectomy. This new bio-barcode PSA assay is
      approximately 300 times more sensitive than commercial immunoassays.
      Significantly, with the barcode assay, every patient in this cohort had a
      measurable serum PSA level after radical prostatectomy. Patients were separated
      into categories based on PSA levels as a function of time. One group of patients
      showed low levels of PSA with no significant increase with time and did not
      recur. Others showed, at some point postprostatectomy, rising PSA levels. The
      majority recurred. Therefore, this new ultrasensitive assay points to significant
      possible outcomes: (i) The ability to tell patients, who have undetectable PSA
      levels with conventional assays, but detectable and nonrising levels with the
      barcode assay, that their cancer will not recur. (ii) The ability to assign
      recurrence earlier because of the ability to measure increasing levels of PSA
      before conventional tools can make such assignments. (iii) The ability to use PSA
      levels that are not detectable with conventional assays to follow the response of
      patients to adjuvant or salvage therapies.

PMID- 19841274
TI  - Degrons in protein substrates program the speed and operating efficiency of the
      AAA+ Lon proteolytic machine.
AB  - AAA+ proteases are ATP-fueled machines that bind protein substrates via a
      degradation tag, unfold the molecule if necessary, and then translocate the
      polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as
      a passive reaction. By contrast, for the AAA+ Lon protease, we show that degron
      tags are also regulatory elements that determine protease activity levels.
      Indeed, different tags fused to the same protein change degradation speeds and
      energetic efficiencies by 10-fold or more. Degron binding to multiple sites in
      the Lon hexamer appears to differentially stabilize specific enzyme
      conformations, including one with high protease and low ATPase activity, and
      results in positively cooperative degradation. These allosteric mechanisms allow
      Lon to operate in either a fast or slow proteolysis mode, according to specific
      physiological needs, and may help maximize degradation of misfolded proteins
      following stress-induced denaturation.

PMID- 19841275
TI  - An amantadine-sensitive chimeric BM2 ion channel of influenza B virus has
      implications for the mechanism of drug inhibition.
AB  - Influenza A virus M2 (A/M2) and the influenza B virus BM2 are both small integral
      membrane proteins that form proton-selective ion channels. Influenza A virus A/M2
      channel is the target of the antiviral drug amantadine (and its methyl derivative
      rimantadine), whereas BM2 channel activity is not affected by the drug. The
      atomic structure of the pore-transmembrane (TM) domain peptide has been
      determined by x-ray crystallography [Stouffer et al. (2008) Nature 451:596-599]
      and of a larger M2 peptide by NMR methods [Schnell and Chou (2008) Nature 451:591
      595]. The crystallographic data show electron density (at 3.5 A resolution) in
      the channel pore, consistent with amantadine blocking the pore of the channel. In
      contrast, the NMR data show 4 rimantadine molecules bound on the outside of the
      helices toward the cytoplasmic side of the membrane. Drug binding includes
      interactions with residues 40-45 and a polar hydrogen bond between rimantadine
      and aspartic acid residue 44 (D44). These 2 distinct drug-binding sites led to 2
      incompatible drug inhibition mechanisms. We have generated chimeric channels
      between amantadine-sensitive A/M2 and amantadine-insensitive BM2 designed to
      define the drug-binding site. Two chimeras containing 5 residues of the A/M2
      ectodomain and residues 24-36 of the A/M2 TM domain show 85%
      amantadine/rimantadine sensitivity and specific activity comparable to that of WT
      BM2. These functional data suggest that the amantadine/rimantadine binding site
      identified on the outside of the 4 helices is not the primary site associated
      with the pharmacologic inhibition of the A/M2 ion channel.

PMID- 19841276
TI  - Plant DNA barcodes and a community phylogeny of a tropical forest dynamics plot
      in Panama.
AB  - The assembly of DNA barcode libraries is particularly relevant within species
      rich natural communities for which accurate species identifications will enable
      detailed ecological forensic studies. In addition, well-resolved molecular
      phylogenies derived from these DNA barcode sequences have the potential to
      improve investigations of the mechanisms underlying community assembly and
      functional trait evolution. To date, no studies have effectively applied DNA
      barcodes sensu strictu in this manner. In this report, we demonstrate that a
      three-locus DNA barcode when applied to 296 species of woody trees, shrubs, and
      palms found within the 50-ha Forest Dynamics Plot on Barro Colorado Island (BCI),
      Panama, resulted in >98% correct identifications. These DNA barcode sequences are
      also used to reconstruct a robust community phylogeny employing a supermatrix
      method for 281 of the 296 plant species in the plot. The three-locus barcode data
      were sufficient to reliably reconstruct evolutionary relationships among the
      plant taxa in the plot that are congruent with the broadly accepted phylogeny of
      flowering plants (APG II). Earlier work on the phylogenetic structure of the BCI
      forest dynamics plot employing less resolved phylogenies reveals significant
      differences in evolutionary and ecological inferences compared with our data and
      suggests that unresolved community phylogenies may have increased type I and type
      II errors. These results illustrate how highly resolved phylogenies based on DNA
      barcode sequence data will enhance research focused on the interface between
      community ecology and evolution.

PMID- 19841278
TI  - Macroevolutionary patterns of defense and pollination in Dalechampia vines:
      adaptation, exaptation, and evolutionary novelty.
AB  - We conducted phylogenetically informed comparative analyses of 81 taxa of
      Dalechampia (Euphorbiaceae) vines and shrubs to assess the roles of historical
      contingency and trait interaction in the evolution of plant-defense and
      pollinator-attraction systems. We asked whether defenses can originate by
      exaptation from preexisting pollinator attractants, or vice versa, whether plant
      defenses show escalation, and if so, whether by enhancing one line of defense or
      by adding new lines of defense. Two major patterns emerged: (i) correlated
      evolution of several complementary lines of defense of flowers, seeds, and
      leaves, and (ii) 5 to 6 losses of the resin reward, followed by redeployment of
      resin for defense of male flowers in 3 to 4 lineages, apparently in response to
      herbivore-mediated selection for defense of staminate flowers upon relaxation of
      pollinator-mediated selection on resin. In all cases, redeployment of resin
      involved reversion to the inferred ancestral arrangement of flowers and
      resiniferous bractlets. Triterpene resin has also been deployed for defense of
      leaves and developing seeds. Other unique defenses against florivores include
      nocturnal closure of large involucral bracts around receptive flowers and
      permanent closure around developing fruits (until opening again upon dehiscence).
      Escalation in one major clade occurred through an early dramatic increase in the
      number of lines of defense and in the other major clade by more limited increases
      throughout the group's evolution. We conclude that preaptations played important
      roles in the evolution of unique defense and attraction systems, and that the
      evolution of interactions with herbivores can be influenced by adaptations for
      pollination, and vice versa.

PMID- 19841277
TI  - Site-specific modification of Alzheimer's peptides by cholesterol oxidation
      products enhances aggregation energetics and neurotoxicity.
AB  - Accumulation of amyloid beta-peptide (Abeta) and tau aggregates, possibly linked
      to age-associated deficiencies in protein homeostasis, appear to cause
      Alzheimer's disease. Schiff-base formation between Abeta and the aldehyde-bearing
      cholesterol oxidation product 3-beta-hydroxy-5-oxo-5,6-secocholestan-6-al is
      known to increase Abeta amyloidogenicity. Here, we synthesized Abeta variants
      site-specifically modified with the cholesterol aldehyde at Asp-1, Lys-16, or Lys
      28, rather than studying mixtures. These distinct modifications have a similar
      effect on the thermodynamic propensity for aggregation, enabling aggregation at
      low concentrations. In contrast, the modification site differentially influences
      the aggregation kinetics; Lys-16-modified Abeta formed amorphous aggregates
      fastest and at the lowest concentration (within 2 h at a concentration of 20 nM),
      followed by the Lys-28 and Asp-1 conjugates. Also, the aggregates resulting from
      Abeta Lys-16 cholesterol aldehyde conjugation were more toxic to primary rat
      cortical neurons than treatment with unmodified Abeta under identical conditions
      and at the same concentration. Our results show that Abeta modification by
      cholesterol derivatives, especially at Lys-16, renders it kinetically and
      thermodynamically competent to form neurotoxic aggregates at concentrations
      approaching the physiologic concentration of Abeta.

PMID- 19841279
TI  - Adenoviral transfer of HIF-1alpha enhances vascular responses to critical limb
      ischemia in diabetic mice.
AB  - Diabetes is a major risk factor for ischemic disease. Treatment options for
      diabetic patients with peripheral arterial disease when revascularization is not
      possible are limited, resulting in a high incidence of limb amputation. We
      evaluated the therapeutic potential of AdCA5, an adenovirus encoding a
      constitutively active form of HIF-1alpha, in a diabetic model of critical limb
      ischemia. Diabetic db/db and nondiabetic db/+ mice were subjected to unilateral
      femoral artery ligation. Limb perfusion, tissue viability, and motor function
      were more severely impaired in db/db mice. Intramuscular injection of AdCA5 into
      the ischemic limb of db/db mice increased the recovery of limb perfusion and
      function, reduced tissue necrosis, rescued the diabetes-associated impairment of
      circulating angiogenic cells, enhanced endothelial nitric oxide synthase
      activation, and increased vessel density and luminal area in the ischemic limb.

PMID- 19841280
TI  - Patient decision aids for prostate cancer treatment: a systematic review of the
      literature.
AB  - Treatment decision-making can be difficult and complex for patients with low-risk
      prostate cancer. To the authors' knowledge, there is no consensus regarding an
      optimal treatment strategy and the choice of therapy involves tradeoffs between
      differing harms and benefits that are sensitive to patient values. In such
      situations, patients are often asked to participate actively in the decision
      making process, and high-quality decisions require a well-informed patient whose
      values and preferences have been taken into consideration. Prior studies have
      indicated that patients have poor knowledge and unrealistic expectations
      regarding treatment, and physician judgments concerning patient preferences are
      often inaccurate. Decision aids (DAs) have been developed to help inform patients
      with low-risk prostate cancer about treatment options and assist in the decision
      making process; however, little is currently known regarding the effects of such
      programs in this population. Thirteen studies of DAs for patients with prostate
      cancer were reviewed and it was found that the use of DAs can improve knowledge,
      encourage more active patient involvement in decision-making, and decrease levels
      of anxiety and distress. The effect of DAs on treatment choice was less clear,
      although fewer patients chose surgery compared with historical controls,
      particularly in Europe. Further studies are needed to determine how best to
      implement DAs into practice, and whether they improve the consistency between
      patient preferences and treatment choice.

PMID- 19841281
TI  - Hypertension, growth, and skeletal maturation in the young: a new look at an old
      idea.

PMID- 19841282
TI  - Nighttime activity influences the evaluation of ambulatory blood pressure
      monitoring.

PMID- 19841283
TI  - Does prorenin exert angiotensin-independent effects in vivo?

PMID- 19841284
TI  - Mineralocorticoid receptors in myocardial infarction.

PMID- 19841285
TI  - Accelarated skeletal maturation in children with primary hypertension.
AB  - It is hypothesized that primary hypertension (PH) is a disorder with origins in
      childhood linked to, at least in part, aberrations of growth and maturation
      processes. To evaluate the possible relation between the rate of biological
      maturity and development of PH, bone age (BA) assessments on the basis of dual x
      ray absorptiometry-derived hand scans were performed in 54 newly diagnosed
      children and adolescents with PH and 54 healthy controls matched for body mass
      index (BMI), age and sex. Chronological age (CA), body height (in centimeters),
      body weight (in kilograms), BMI (in kilograms per meter squared), and blood
      pressure were assessed. Healthy controls had a mean BA of 14.7+/-2.3 years that
      was not significantly different from their mean CA of 14.2+/-2.1 years. In the PH
      group, the BA of 16.0+/-2.0 years was higher by 1.9+/-0.9 years compared with
      their CA of 14.1+/-2.0 years (P<0.0001). The magnitude of acceleration of
      skeletal maturation (BA-CA) and its prevalence (88.9%) were significantly higher
      in PH compared with BMI-matched controls (37.0%; chi(2)=31.4; P<0.0001). BA-CA
      values of PH patients were higher by 1.24 years in normal weight (P<0.0001), 1.80
      years in overweight (P<0.01), and 1.40 years in obese (P<0.0001) subgroups of BMI
      z score-matched controls. Stepwise regression revealed that predictors of blood
      pressure status from normotension through prehypertension stages 1 and 2 of
      hypertension were BA-CA (beta=0.530; P<0.0.001), height (beta=-0.379; P<0.01),
      and CA (beta=0.298; P<0.05; R(2)=0.43). In conclusion, irrespective of BMI,
      advanced biological maturation should be considered as an independent marker for
      the development of hypertension.

PMID- 19841286
TI  - Prorenin contributes to angiotensin peptide formation in transgenic rats with rat
      prorenin expression targeted to the liver.
AB  - We reported previously that targeted expression of rat prorenin to the liver
      under the control of the human alpha1-antitrypsin promoter increased plasma
      prorenin levels by several-hundred-fold in male transgenic rats and caused
      cardiac hypertrophy, severe renal lesions, and myocardial fibrosis by 20 weeks of
      age, despite normal blood pressure. We examined the evolution of the phenotype of
      male transgenic rats over 12 months and the effects of binephrectomy on the renin
      angiotensin (Ang) system. Plasma prorenin levels were >1000-fold higher than in
      wild type littermates, whereas plasma and renal Ang II levels were no different
      from wild-type (WT) levels, and kidney renin levels were suppressed in transgenic
      rats. In contrast to our earlier report, transgenic rats had increased systolic
      blood pressure at 3 to 12 months of age, and only modest renal lesions and
      myocardial fibrosis were evident after 6 months of age. Binephrectomy reduced
      plasma renin activity and concentration and prorenin levels by 50% to 80% and Ang
      II levels by 90% in WT rats. By contrast, binephrectomy increased plasma renin
      activity and concentration and prorenin levels by 52.0-, 13.0-, and 5.8-fold,
      respectively, without change in Ang II levels in transgenic rats. We conclude
      that, in the animals studied in this report, elevated prorenin levels did not
      cause renal lesions or myocardial fibrosis during the first 6 months of age. Ang
      peptide formation consequent to the increased prorenin levels prevented reduction
      of Ang II levels after binephrectomy and was likely to have contributed to
      hypertension, cardiac hypertrophy, and suppression of kidney renin levels in
      these transgenic rats.

PMID- 19841287
TI  - Moderate exercise decreases inflammation and oxidative stress in hypertension:
      but what are the mechanisms?

PMID- 19841288
TI  - Glucocorticoids activate cardiac mineralocorticoid receptors during experimental
      myocardial infarction.
AB  - Myocardial ischemia-reperfusion leads to significant changes in redox state,
      decreased postischemic functional recovery, and cardiomyocyte apoptosis, with
      development and progression of heart failure. Ischemia-reperfusion in the
      isolated perfused rat heart has been used as a model of heart failure.
      Clinically, mineralocorticoid receptor blockade in heart failure decreases
      morbidity and mortality versus standard care alone. The effects of
      corticosteroids on infarct area and apoptosis were determined in rat hearts
      subjected to 30 minutes of ischemia and 2.5 hours of reperfusion. Both
      aldosterone and cortisol increased infarct area and apoptotic index, an effect
      half-maximal between 1 and 10 nM and reversed by spironolactone. Dexamethasone
      and mifepristone aggravated infarct area and apoptotic index, similarly reversed
      by spironolactone. Spironolactone alone reduced infarct area and apoptotic index
      below ischemia-reperfusion alone, in hearts from both intact and adrenalectomized
      rats. The present study shows that cardiac damage is aggravated by activation of
      mineralocorticoid receptors by aldosterone or cortisol or of glucocorticoid
      receptors by dexamethasone. Mifepristone unexpectedly acted as a glucocorticoid
      receptor agonist, for which there are several precedents. Spironolactone
      protected cardiomyocytes via inverse agonist activity at mineralocorticoid
      receptors, an effect near maximal at a relatively low dose (10 nM).
      Spironolactone acts not merely by excluding corticosteroids from
      mineralocorticoid receptors but as a protective inverse agonist at low
      concentration. Mineralocorticoid receptor antagonists may, thus, provide an
      additional therapeutic advantage in unstable angina and acute myocardial
      infarction.

PMID- 19841290
TI  - MicroRNAs and beyond: the heart reveals its treasures.

PMID- 19841289
TI  - Role of proinflammatory cytokines and redox homeostasis in exercise-induced
      delayed progression of hypertension in spontaneously hypertensive rats.
AB  - Hypertension is a well-known risk factor for various cardiovascular diseases.
      Recently, exercise has been recommended as a part of lifestyle modification for
      all hypertensive patients. However, the precise mechanisms of exercise training
      (ExT)-induced effects on the development of hypertension are poorly understood.
      Therefore, we hypothesized that chronic ExT would delay the progression of
      hypertension in young spontaneously hypertensive rats (SHRs). In addition, we
      explored whether the beneficial effects of chronic ExT were mediated by reduced
      proinflammatory cytokines and improved redox status. We also investigated the
      involvement of nuclear factor-kappaB in exercise-induced effects. To test our
      hypotheses, young normotensive (Wistar-Kyoto) and SHRs were given moderate
      intensity ExT for 16 weeks. Blood pressure was determined by the tail-cuff
      method, and cardiac function was assessed by echocardiography. Myocardial total
      reactive oxygen species and superoxide production were measured by electron
      paramagnetic resonance spectroscopy; tumor necrosis factor-alpha, interleukin
      1beta, gp91(phox), and inducible NO synthase by real-time PCR; and nuclear factor
      kappaB activity by electrophoretic mobility shift assay. Chronic ExT in
      hypertensive rats resulted in significantly reduced blood pressure, reduced
      concentric hypertrophy, and improved diastolic function. ExT significantly
      reduced proinflammatory cytokines and inducible NO synthase, attenuated total
      reactive oxygen species and superoxide production, and increased antioxidants in
      SHRs. ExT also resulted in increased NO production and decreased nuclear factor
      kappaB activity in SHRs. In summary, chronic ExT delays the progression of
      hypertension and improves cardiac function in young SHRs; these ExT-induced
      beneficial effects are mediated by reduced proinflammatory cytokines and improved
      redox homeostasis via downregulation of nuclear factor-kappaB.

PMID- 19841291
TI  - Relation of serum leptin to blood pressure of Japanese in Japan and Japanese
      Americans in Hawaii.
AB  - Data from animal studies clearly indicate an association between leptin and
      hypertension; results of human studies are less concordant. We investigated the
      role of leptin in obesity-related higher blood pressure (BP) in Japanese
      Americans living in Hawaii and Japanese in Japan. Serum leptin and BP were
      examined by standardized methods in men and women ages 40 to 59 years from 2
      population samples, one Japanese American in Hawaii (88 men and 94 women) and the
      other Japanese in central Japan (123 men and 111 women). Multiple linear
      regression models were used to assess role of leptin in obesity-related higher
      BP. Across quartiles of leptin, there were significantly higher mean body mass
      index levels, systolic BP, and diastolic BP for both sexes and sites (P<0.01 to
      0.02). In multivariate regression analyses using all of the data combined,
      relations of body mass index and leptin to systolic BP and diastolic BP remained
      significant with the interaction term (body mass index x log-leptin) in the
      models (P<0.01 to <0.05). These findings are consistent with the inference that
      leptin may be an independent mediator for obesity-related elevations in BP.

PMID- 19841292
TI  - Reinforcing feedback loop of renal cyclic guanosine 3' 5' -monophosphate and
      interstitial hydrostatic pressure in pressure-natriuresis.
AB  - This study addresses the hypothesis that renal interstitial (RI) cGMP, a
      modulator of pressure-natriuresis, exerts its effect through a relationship with
      renal interstitial hydrostatic pressure (RIHP). Increasing renal perfusion
      pressure in Sprague-Dawley rats led to increases in RIHP (5.2+/-0.6 to 10.9+/-1.6
      mm Hg; P<0.01), urine sodium excretion (0.062+/-0.009 to 0.420+/-0.068
      micromol/min per gram; P<0.01), and RI cGMP (3.5+/-0.8 to 9.5+/-1.7 fmol/min;
      P<0.01), and these effects were blocked by partial renal decapsulation. Infusion
      of cGMP into the RI compartment of decapsulated animals restored natriuresis
      (0.067+/-0.010 to 0.310+/-0.061 micromol/min per gram; P<0.01). These changes
      were independent of changes in glomerular filtration rate . Artificially
      increasing RIHP in normotensive animals increased RI cGMP (4.1+/-0.6 to 6.9+/-0.7
      fmol/min; P<0.01) and urine sodium excretion (0.071+/-0.013 to 0.179+/-0.039
      micromol/min per gram; P<0.05). Coinfusion of organic anion transport-inhibitor
      probenecid, or soluble guanylyl cyclase inhibitor 1-H(1,2,4) oxadiazolo
      (4,2)quinoxalin-1-one, abolished these effects. Infusion of cGMP into the RI
      compartment of normotensive animals increased RIHP (6.7+/-0.4 to 10.3+/-0.9 mm
      Hg; P<0.001). Exogenous RI cGMP delivery did not affect total, cortical, or
      medullary renal blood flow. These studies suggest that extracellular RI cGMP is
      required for the natriuresis observed after increases in renal perfusion pressure
      and RIHP and that cGMP acts via a tubule mechanism. The results support an
      intrarenal positive-feedback loop wherein RI cGMP increases RIHP, which, in turn,
      increases RI cGMP, contributing to the reinforcement of pressure-natriuresis.

PMID- 19841293
TI  - Does junk food lead to heart failure? Importance of dietary macronutrient
      composition in hypertension.

PMID- 19841294
TI  - Dietary-induced obesity hastens the progression from concentric cardiac
      hypertrophy to pump dysfunction in spontaneously hypertensive rats.
AB  - We explored whether dietary-induced obesity hastens the transition from
      concentric left ventricular (LV) hypertrophy to pump dysfunction in spontaneously
      hypertensive rats (SHRs) and the mechanisms thereof. After feeding rats a diet
      for 4 to 5 months, obesity was induced in SHRs and Wistar-Kyoto (WKY) control
      rats. Obesity was not associated with abnormal blood glucose control
      (glycosylated hemoglobin) or with increases in systolic blood pressure. However,
      in SHRs, but not in WKY rats, obesity was associated with a reduced LV chamber
      systolic function, as determined by echocardiography, and in isolated perfused
      heart studies. A marked increase in LV end diastolic diameter and a right shift
      in the LV diastolic pressure-volume relation were noted in obese SHRs but not in
      obese WKY rats. Moreover, LV intrinsic myocardial systolic function, as
      determined from the slope of the linearized LV systolic stress-strain
      relationship (LV myocardial end systolic elastance), was markedly reduced in
      obese as compared with lean SHRs, whereas LV myocardial end systolic elastance
      was maintained in obese WKY rats. Obesity increased LV weight, cardiomyocyte
      width, cardiomyocyte apoptosis (TUNEL), the activity of myocardial matrix
      metalloproteinases (zymography), and serum leptin concentrations in SHRs but not
      in WKY rats. In conclusion, SHRs are susceptible to the adverse effects of
      dietary-induced obesity on the heart, an effect that hastens the progression from
      concentric LV hypertrophy to pump dysfunction independent of blood pressure
      changes or alterations in glycosylated hemoglobin. This effect may be mediated
      through a proclivity of SHRs to developing both obesity-induced effects on
      cardiomyocyte apoptosis and activation of myocardial collagenases through leptin
      resistance and obesity-induced hypertrophy.

PMID- 19841295
TI  - Prostaglandin-based renal protection against contrast-induced acute kidney
      injury.

PMID- 19841296
TI  - Closer look at genetic testing in long-QT syndrome: will DNA diagnostics ever be
      enough?

PMID- 19841297
TI  - N-terminal pro-B-type natriuretic peptide is a major predictor of the development
      of atrial fibrillation: the Cardiovascular Health Study.
AB  - BACKGROUND: Atrial fibrillation (AF), the most common cardiac rhythm abnormality,
      is associated with significant morbidity, mortality, and healthcare expenditures.
      Elevated B-type natriuretic peptide levels have been associated with the risk of
      heart failure, AF, and mortality. METHODS AND RESULTS: The relation between N
      terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5445
      Cardiovascular Health Study participants with the use of relative risk regression
      for predicting prevalent AF and Cox proportional hazards for predicting incident
      AF. NT-proBNP levels were strongly associated with prevalent AF, with an
      unadjusted prevalence ratio of 128 for the highest quintile (95% confidence
      interval, 17.9 to 913.3; P<0.001) and adjusted prevalence ratio of 147 for the
      highest quintile (95% confidence interval, 20.4 to 1064.3; P<0.001) compared with
      the lowest. After a median follow-up of 10 years (maximum of 16 years), there
      were 1126 cases of incident AF (a rate of 2.2 per 100 person-years). NT-proBNP
      was highly predictive of incident AF, with an unadjusted hazard ratio of 5.2 (95%
      confidence interval, 4.3 to 6.4; P<0.001) for the development of AF for the
      highest quintile compared with the lowest; for the same contrast, NT-proBNP
      remained the strongest predictor of incident AF after adjustment for an extensive
      number of covariates, including age, sex, medication use, blood pressure,
      echocardiographic parameters, diabetes mellitus, and heart failure, with an
      adjusted hazard ratio of 4.0 (95% confidence interval, 3.2 to 5.0; P<0.001).
      CONCLUSIONS: In a community-based population of older adults, NT-proBNP was a
      remarkable predictor of incident AF, independent of any other previously
      described risk factor.

PMID- 19841298
TI  - Prevalence of the congenital long-QT syndrome.
AB  - BACKGROUND: The prevalence of genetic arrhythmogenic diseases is unknown. For the
      long-QT syndrome (LQTS), figures ranging from 1:20 000 to 1:5000 were published,
      but none was based on actual data. Our objective was to define the prevalence of
      LQTS. METHODS AND RESULTS: In 18 maternity hospitals, an ECG was performed in 44
      596 infants 15 to 25 days old (43 080 whites). In infants with a corrected QT
      interval (QTc) >450 ms, the ECG was repeated within 1 to 2 weeks. Genetic
      analysis, by screening 7 LQTS genes, was performed in 28 of 31 (90%) and in 14 of
      28 infants (50%) with, respectively, a QTc >470 ms or between 461 and 470 ms. A
      QTc of 451 to 460, 461 to 470, and >470 ms was observed in 177 (0.41%), 28
      (0.06%), and 31 infants (0.07%). Among genotyped infants, disease-causing
      mutations were found in 12 of 28 (43%) with a QTc >470 ms and in 4 of 14 (29%)
      with a QTc of 461 to 470 ms. One genotype-negative infant (QTc 482 ms) was
      diagnosed as affected by LQTS on clinical grounds. Among family members of
      genotype-positive infants, 51% were found to carry disease-causing mutations. In
      total, 17 of 43 080 white infants were affected by LQTS, demonstrating a
      prevalence of at least 1:2534 apparently healthy live births (95% confidence
      interval, 1:1583 to 1:4350). CONCLUSIONS: This study provides the first data
      based estimate of the prevalence of LQTS among whites. On the basis of the
      nongenotyped infants with QTc between 451 and 470 ms, we advance the hypothesis
      that this prevalence might be close to 1:2000. ECG-guided molecular screening can
      identify most infants affected by LQTS and unmask affected relatives, thus
      allowing effective preventive measures.

PMID- 19841299
TI  - Iloprost prevents contrast-induced nephropathy in patients with renal dysfunction
      undergoing coronary angiography or intervention.
AB  - BACKGROUND: The prevention of contrast-induced nephropathy, which accounts for
      considerable morbidity and mortality, remains a vexing problem. Contrast-induced
      renal vasoconstriction is believed to play a pivotal role in the pathogenesis of
      contrast-induced nephropathy. The aim of this study was to examine the efficacy
      of the prostacyclin analog iloprost in preventing contrast-induced nephropathy in
      patients with renal dysfunction undergoing a coronary procedure. METHODS AND
      RESULTS: We conducted a randomized, double-blind, placebo-controlled trial of
      iloprost in 208 patients with a serum creatinine concentration >or=1.4 mg/dL who
      underwent coronary angiography and/or intervention. Iloprost 1 ng kg(-1) min(-1)
      or placebo was administered intravenously beginning 30 to 90 minutes before and
      ending 4 hours after the procedure. Contrast-induced nephropathy was defined by
      an absolute increase in serum creatinine >or=0.5 mg/dL or a relative increase
      >or=25% measured 2 to 5 days after the procedure. Contrast-induced nephropathy
      occurred in 23 of the 105 patients (22%) in the control group and in 8 of the 103
      patients (8%) in the iloprost group (odds ratio, 0.29; 95% confidence interval,
      0.12 to 0.69; P=0.005). In the control group, the estimated glomerular filtration
      rate declined from 49.7+/-15.5 to 46.6+/-16.6 mL min(-1) 1.73 m(-2) (P=0.01). In
      the iloprost group, the estimated glomerular filtration rate increased marginally
      from 47.5+/-14.5 to 48.6+/-16.1 mL min(-1) 1.73 m(-2) (P=0.26). The mean absolute
      estimated glomerular filtration rate decline in the control group was greater
      than its change in the iloprost group (difference, 4.2 mL min(-1) 1.73 m(-2); 95%
      confidence interval, 1.1 to 7.3; P=0.008). CONCLUSIONS: Prophylactic
      administration of iloprost may protect against contrast-induced nephropathy in
      high-risk patients undergoing a coronary procedure.

PMID- 19841300
TI  - Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from
      benign variants.
AB  - BACKGROUND: Genetic testing for long-QT syndrome (LQTS) has diagnostic,
      prognostic, and therapeutic implications. Hundreds of causative mutations in 12
      known LQTS-susceptibility genes have been identified. Genetic testing that
      includes the 3 most commonly mutated genes is available clinically.
      Distinguishing pathogenic mutations from innocuous rare variants is critical to
      the interpretation of test results. We sought to quantify the value of mutation
      type and gene/protein region in determining the probability of pathogenicity for
      mutations. METHODS AND RESULTS: Type, frequency, and location of mutations across
      KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3) were compared between 388 unrelated
      "definite" (clinical diagnostic score >or=4 and/or QTc >or=480 ms) cases of LQTS
      and >1300 healthy controls for each gene. From these data, estimated predictive
      values (percent of mutations found in definite cases that would cause LQTS) were
      determined according to mutation type and location. Mutations were 10 times more
      common in cases than controls (0.58 per case versus 0.06 per control). Missense
      mutations were the most common, accounting for 78%, 67%, and 89% of mutations in
      KCNQ1, KCNH2, and SCN5A in cases and >95% in controls. Nonmissense mutations have
      an estimated predictive value >99% regardless of location. In contrast, location
      appears to be critical for characterizing missense mutations. Relative frequency
      of missense mutations between cases and controls ranged from approximately 1:1 in
      the SCN5A interdomain linker to infinity in the pore, transmembrane, and linker
      in KCNH2. These correspond to estimated predictive values ranging from 0% in the
      interdomain linker of SCN5A to 100% in the transmembrane/linker/pore regions of
      KCNH2. The estimated predictive value is also high in the linker, pore,
      transmembrane, and C terminus of KCNQ1 and the transmembrane/linker of SCN5A.
      CONCLUSIONS: Distinguishing pathogenic mutations from rare variants is of
      critical importance in the interpretation of genetic testing in LQTS. Mutation
      type, mutation location, and ethnic-specific BACKGROUND: should be viewed as
      variants of uncertain significance and prompt further investigation to clarify
      the likelihood of disease causation. However, mutations in regions such as the
      transmembrane, linker, and pore of KCNQ1 and KCNH2 may be defined confidently as
      high-probability LQTS-causing mutations. These findings will have implications
      for other genetic disorders involving mutational analysis.

PMID- 19841301
TI  - CC chemokine receptor-1 activates intimal smooth muscle-like cells in graft
      arterial disease.
AB  - BACKGROUND: Graft arterial disease (GAD) limits long-term solid-organ allograft
      survival. The thickened intima in GAD contains smooth muscle-like cells (SMLCs),
      leukocytes, and extracellular matrix. The intimal SMLCs in mouse GAD lesions
      differ from medial smooth muscle cells in their function and phenotype. Although
      intimal SMLCs may originate by migration and modulation of donor medial cells or
      by recruitment of host-derived precursors, the mechanisms that underlie their
      localization within grafts and the factors that drive these processes remain
      unclear. METHODS AND RESULTS: This study of aortic transplantation in mice
      demonstrated an important function for chemokines beyond their traditional role
      in leukocyte recruitment and activation. Intimal SMLCs, but not medial smooth
      muscle cells, express functional CC chemokine receptor-1 (CCR1) and respond to
      RANTES by increased migration and proliferation. Although RANTES infusion in vivo
      promoted inflammatory cell accumulation in the adventitia of aortic allografts of
      wild-type and CCR1-deficient recipients, it increased GAD intimal thickening with
      SMLC proliferation in only the wild-type hosts. Aortic allografts transplanted
      into CCR1-deficient mice after wild-type bone marrow transplantation did not
      develop intimal lesions, which indicates that CCR1-bearing inflammatory cells do
      not contribute to intimal lesion formation. Moreover, RANTES induced SMLC
      proliferation in vitro but did not promote medial smooth muscle cell growth.
      Blockade of CCR5 attenuated RANTES-induced T-cell and monocyte/macrophage
      proliferation but did not affect RANTES-induced SMLC proliferation, consistent
      with a larger role of CCR1-binding chemokines in SMLC migration and proliferation
      and GAD development. CONCLUSIONS: These studies provide a novel mechanistic
      insight into the formation of vascular intimal hyperplasia and suggest a novel
      therapeutic strategy for preventing allograft arteriopathy.

PMID- 19841302
TI  - Peripheral vascular adaptation and orthostatic tolerance in Fontan physiology.
AB  - BACKGROUND: The Fontan circulation is critically dependent on elevated venous
      pressures to sustain effective venous return. We hypothesized that chronically
      increased systemic venous pressures lead to adaptive changes in regional and
      peripheral vessels to maintain cardiac output, especially when patients are
      upright. METHODS AND RESULTS: Nine post-Fontan procedure patients (aged 13 to 24
      years) and 6 age- and sex-matched controls were compared with techniques to
      measure circulatory responses (peripheral and compartmental blood flow, venous
      capacity, and microvascular filtration). Parameters studied included strain-gauge
      plethysmography measures of peripheral circulatory function, regional blood
      volume distribution by impedance plethysmography, and head-up tilt testing.
      Important differences between Fontan patients and controls were seen in several
      vascular compartments: (1) Calf capacitance was lower (median, 3.5 versus 5.5
      mL/100 mL tissue; P=0.005), and resting venous pressure was higher (13.0 versus
      10.5 mm Hg; P=0.004); (2) higher leg arterial resistance was observed (32.1
      versus 22.2; P=0.03); (3) microvascular filtration pressures and threshold for
      edema were elevated; and (4) with head-up tilt testing, splanchnic flow was not
      reduced in Fontan patients versus controls (fractional change, +4% versus -32%;
      P=0.004), and splanchnic arterial resistance did not increase as expected
      (fractional change, +8% versus +79%; P=0.003). CONCLUSIONS: Reduced venous
      compliance and increased filtration thresholds may act as adaptive mechanisms in
      maintaining venous return in Fontan circulation. Well-compensated Fontan subjects
      demonstrate superior orthostatic tolerance resulting from decreased compartmental
      fluid shifts in response to head-up tilt and higher vascular resistance. This
      results from increased venous stiffness and decreased splanchnic capacitance and
      may also be an adaptive mechanism to maintain venous return in these patients
      while standing.

PMID- 19841303
TI  - Relation between alkaline phosphatase, serum phosphate, and all-cause or
      cardiovascular mortality.
AB  - BACKGROUND: Higher levels of serum alkaline phosphatase (AlkP) are associated
      with excess mortality in dialysis patients, but whether AlkP is associated with
      adverse outcomes among people without kidney failure is unknown. METHODS AND
      RESULTS: We first analyzed the association between AlkP and cardiovascular
      outcomes among 4115 participants with a previous myocardial infarction (the
      Cholesterol And Recurrent Events [CARE] study). Results were validated by
      analyzing the association between AlkP and mortality in an independent sample of
      14,716 adults from the general US population (the Third National Health and
      Nutrition Examination Survey). A graded, independent association was noted
      between baseline tertile of AlkP and the adjusted hazard ratio of all-cause
      mortality in CARE participants (P(trend)=0.02). After adjustment for serum
      phosphate, hepatic enzymes, and other potential confounders, participants with
      AlkP in the highest tertile had an adjusted hazard ratio of 1.43 (95% confidence
      interval 1.08 to 1.89) compared with those in the lowest tertile. Multivariable
      adjusted associations between higher AlkP and all-cause and cardiovascular
      mortality were present in the Third National Health and Nutrition Examination
      Survey (P(trend) across tertiles of AlkP=0.006 and 0.038, respectively). Findings
      from both CARE and the Third National Health and Nutrition Examination Survey
      were similar among individuals with and without evidence of kidney disease,
      defined by estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2).
      CONCLUSIONS: We found an independent relation between higher levels of AlkP and
      adverse outcomes among survivors of myocardial infarction and in a general
      population sample. The excess risk of death was present in people without
      evidence of kidney disease and was particularly high among people with higher
      levels of both AlkP and serum phosphate.

PMID- 19841304
TI  - Tobacco smoke exposure in either the donor or recipient before transplantation
      accelerates cardiac allograft rejection, vascular inflammation, and graft loss.
AB  - BACKGROUND: Tobacco exposure in cardiac transplant recipients, before and after
      transplantation, may increase the risk of cardiac allograft vasculopathy and
      allograft loss, but no direct evidence for this phenomenon is forthcoming. In
      this experimental study, we investigated early consequences of tobacco smoke
      exposure in cardiac transplant donors and recipients with an emphasis on
      alloinflammatory mediators of graft outcome. METHODS AND RESULTS: Using
      heterotopic rat cardiac transplantation, we tested the effects of donor or
      recipient tobacco smoke exposure in 6 groups of animals (rat heterotopic cardiac
      transplantation) as follows: tobacco-naive allogeneic rejecting controls (n=6),
      tobacco-naive nonrejecting controls (n=3; killed on day 5 to simulate survival
      times of tobacco-treated animals), isografts (n=3), both donor and recipient rats
      exposed to tobacco smoke (n=4), only donor rats exposed to tobacco smoke (n=7),
      and only recipient rats exposed to tobacco smoke (n=6). Polymerase chain reaction
      studies of tissue and peripheral (systemic) protein expression were performed to
      evaluate inflammatory (tumor necrosis factor-alpha, interferon-gamma, interleukin
      6) and alloimmune (interleukin-1 receptor 2, programmed cell death-1, and stromal
      cell-derived factor-1) pathways, as was histological analysis of the cardiac
      allografts. Our experiments reveal that pretransplantation tobacco exposure in
      donors and/or recipients results in heightened systemic inflammation and
      increased oxidative stress, reduces posttransplantation cardiac allograft
      survival by 33% to 57%, and increases intragraft inflammation (tumor necrosis
      factor-alpha, interferon-gamma, interleukin-6) and alloimmune activation (CD3,
      interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived
      factor-1) with consequent myocardial and vascular destruction. CONCLUSIONS: These
      sentinel findings confirm that tobacco smoke exposure in either donors or
      recipients leads to accelerated allograft rejection, vascular inflammation, and
      graft loss. Molecular pathways that intersect as arbiters in this phenomenon
      include instigation of alloimmune activation associated with tobacco smoke
      induced inflammation.

PMID- 19841305
TI  - Images in cardiovascular medicine: transapical aortic valve implantation in a
      patient with severe aortic stenosis and Pott disease.

PMID- 19841306
TI  - Letter by Corrado et al regarding article, "sudden deaths in young competitive
      athletes: analysis of 1866 deaths in the United States, 1980-2006".

PMID- 19841308
TI  - Cardioversion: past, present, and future.

PMID- 19841309
TI  - The ECG in diabetes mellitus.

PMID- 19841310
TI  - Images in cardiovascular medicine: development of carotid intraplaque hemorrhage
      demonstrated by serial magnetic resonance imaging.

PMID- 19841311
TI  - Toward efficient trials in colorectal cancer: the ARCAD Clinical Trials Program.

PMID- 19841313
TI  - Selection bias clouds apparent benefit of longer hormone duration.

PMID- 19841315
TI  - Revisiting the concept of phenotypically distinct malignant pancreatic stem-cell
      subsets based on limiting dilution transplantation assays.

PMID- 19841316
TI  - How should we prevent hematologic relapse of acute promyelocytic leukemia?

PMID- 19841318
TI  - Metastatic disease response to treatment: how many lesions to measure?

PMID- 19841320
TI  - Breast cancer classification: the dialogue is open.

PMID- 19841321
TI  - Phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients
      with advanced non-small-cell lung cancer: NCCTG and SWOG study N0426.
AB  - PURPOSE: To evaluate the efficacy and toxicity of pemetrexed combined with
      bevacizumab as second-line therapy for patients with advanced non-small-cell lung
      cancer (NSCLC) and to correlate allelic variants in pemetrexed-metabolizing genes
      with clinical outcome. PATIENTS AND METHODS: Patients with previously treated
      NSCLC received pemetrexed (500 mg/m(2) intravenous) combined with bevacizumab (15
      mg/kg intravenous) every 3 weeks. The primary end point, evaluated using a one
      stage Fleming design for detecting a true success rate of at least 70%, was the
      proportion of patients who were progression free and on treatment at 3 months.
      Polymorphisms in genes responsible for pemetrexed transport (reduced folate
      carrier [SLC19A1]) and metabolism (folylpolyglutamate synthase [FPGS] and gamma
      glutamyl hydrolase [GGH]) evaluated in germline DNA (blood) were correlated with
      treatment outcome. RESULTS: Forty-eight evaluable patients (14 females and 34
      males) received a median of four cycles (range, one to 20 cycles). The most
      common grade 3 or 4 nonhematologic adverse events (AEs) were fatigue (13%),
      dyspnea (10%), and thrombosis (10%). Grade 3 or 4 hematologic AEs were
      neutropenia (19%) and lymphopenia (13%). Twenty-four (57%; 95% CI, 41% to 72%) of
      the first 42 patients met the success criteria. Median overall survival (OS) and
      progression-free survival (PFS) times were 8.6 and 4.0 months, respectively. The
      exon 6 (2522)C-->T polymorphism in SLC19A1 correlated with 3-month progression
      free status (P = .01) and with PFS (P = .05). The IVS1(1307)C-->T polymorphism in
      GGH correlated with OS (P = .04). CONCLUSION: The study did not meet its primary
      end point. However, the median PFS time of 4 months is promising. Pharmacogenetic
      studies in larger cohorts are needed to definitively identify polymorphisms that
      predict for survival and toxicity of pemetrexed.

PMID- 19841322
TI  - American Society of Clinical Oncology 2009 clinical evidence review on
      radiofrequency ablation of hepatic metastases from colorectal cancer.
AB  - PURPOSE: To review the evidence about the efficacy and utility of radiofrequency
      ablation (RFA) for hepatic metastases from colorectal cancer (CRHM). METHODS: The
      American Society of Clinical Oncology (ASCO) convened a panel to conduct and
      analyze a comprehensive systematic review of the RFA literature from Medline and
      the Cochrane Collaboration Library. RESULTS: Because data were considered
      insufficient to form the basis of a practice guideline, ASCO has instead
      published a clinical evidence review. The evidence is from single-arm,
      retrospective, and prospective trials. No randomized controlled trials have been
      included. The following three clinical issues were considered by the panel: the
      efficacy of surgical hepatic resection versus RFA for resectable tumors; the
      utility of RFA for unresectable tumors; and RFA approaches (open, laparoscopic,
      or percutaneous). Evidence suggests that hepatic resection improves overall
      survival (OS), particularly for patients with resectable tumors without
      extrahepatic disease. Careful patient and tumor selection is discussed at length
      in the literature. RFA investigators report a wide variability in the 5-year
      survival rate (14% to 55%) and local tumor recurrence rate (3.6% to 60%). The
      reported mortality rate was low (0% to 2%), and the major complications rate was
      commonly reported to be between 6% and 9%. RFA is currently performed with all
      three approaches. CONCLUSION: There is a compelling need for more research to
      determine the efficacy and utility of RFA to increase local recurrence-free,
      progression-free, and disease-free survival as well as OS for patients with CRHM.
      Clinical trials have established that hepatic resection can improve OS for
      patients with resectable CRHM.

PMID- 19841323
TI  - Cancer during pregnancy: an analysis of 215 patients emphasizing the obstetrical
      and the neonatal outcomes.
AB  - PURPOSE: The aim of this study was to assess the management and the obstetrical
      and neonatal outcomes of pregnancies complicated by cancer. PATIENTS AND METHODS:
      In an international collaborative setting, patients with invasive cancer
      diagnosed during pregnancy between 1998 and 2008 were identified. Clinical data
      regarding the cancer diagnosis and treatment and the obstetric and neonatal
      outcomes were collected and analyzed. RESULTS: Of 215 patients, five (2.3%) had a
      pregnancy that ended in a spontaneous miscarriage and 30 (14.0%) pregnancies were
      interrupted. Treatment was initiated during pregnancy in 122 (56.7%) patients and
      postpartum in 58 (27.0%) patients. The most frequently encountered cancer types
      were breast cancer (46%), hematologic malignancies (18%), and dermatologic
      malignancies (10%). The mean gestational age at delivery was 36.3 +/- 2.9 weeks.
      Delivery was induced in 71.7% of pregnancies, and 54.2% of children were born
      preterm. In the group of patients prenatally exposed to cytotoxic treatment, the
      prevalence of preterm labor was increased (11.8%; P = .012). Furthermore, in this
      group a higher proportion of small-for-gestational-age children (birth weight
      below 10th percentile) was observed (24.2%; P = .001). Of all neonates, 51.2%
      were admitted to a neonatal intensive care unit, mainly (85.2%) because of
      prematurity. There was no increased incidence of congenital malformations.
      CONCLUSION: Pregnant cancer patients should be treated in a multidisciplinary
      setting with access to maternal and neonatal intensive care units. Prevention of
      iatrogenic prematurity appears to be an important part of the treatment strategy.

PMID- 19841324
TI  - Costs and benefits of the national cancer institute central institutional review
      board.
AB  - PURPOSE: In 2001, the National Cancer Institute (NCI) formed the Central
      Institutional Review Board (CIRB) to conduct a single human subjects review for
      its multisite phase III oncology trials. The goal of this study was to assess
      whether NCI's CIRB was associated with lower effort, time, and cost in processing
      adult phase III oncology trials. METHODS: We conducted an observational study and
      compared sites affiliated with the NCI CIRB to unaffiliated sites that used their
      local IRB for review. Oncology research staff and IRB staff were surveyed to
      understand effort and timing. Response rates were 60% and 42%, respectively.
      Analysis of these survey data yielded information on effort, timing, and costs.
      We combined these data with CIRB operational data to determine the net savings of
      the CIRB using a societal perspective. RESULTS: CIRB affiliation was associated
      with faster reviews (33.9 calendar days faster on average), and 6.1 fewer hours
      of research staff effort. CIRB affiliation was associated with a savings of $717
      per initial review. The estimated cost of running the CIRB was $161,000 per
      month. The CIRB yielded a net cost of approximately $55,000 per month from a
      societal perspective. Whether the CIRB results in higher or lower quality reviews
      was not assessed because there is no standard definition of review quality.
      CONCLUSION: The CIRB was associated with decreases in investigator and IRB staff
      effort and faster protocol reviews, although savings would be higher if
      institutions used the CIRB as intended.

PMID- 19841325
TI  - Suicide ideation in adult survivors of childhood cancer: a report from the
      Childhood Cancer Survivor Study.
AB  - PURPOSE: To evaluate risk of suicide ideation (SI) after childhood cancer,
      prevalence of SI in a cohort of adult survivors of pediatric cancers was compared
      with prevalence in a sibling comparison group. The relationship of SI to cancer
      treatment and current health was examined, and the hypothesis that poor physical
      health is significantly associated with suicidality, after adjusting for
      depression, was specifically tested. METHODS: Nine thousand one hundred twenty
      six adult survivors of childhood cancer and 2,968 siblings enrolled onto the
      Childhood Cancer Survivor Study completed a survey describing their demographics
      and medical and psychological functioning, including SI in the prior week.
      RESULTS: Of survivors, 7.8% reported SI compared with 4.6% of controls (odds
      ratio = 1.79; 95% CI, 1.4 to 2.4). Suicidality was unrelated to age, age at
      diagnosis, sex, cancer therapy, recurrence, time since diagnosis, or second
      malignancy. SI was associated with primary CNS cancer diagnosis, depression, and
      poor health outcomes including chronic conditions, pain, and poor global health
      rating. A logistic regression analysis showed that poor current physical health
      was significantly associated with SI even after adjusting for cancer diagnosis
      and depression. CONCLUSION: Adult survivors of childhood cancers are at increased
      risk for SI. Risk of SI is related to cancer diagnosis and post-treatment mental
      and physical health, even many years after completion of therapy. The association
      of suicidal symptoms with physical health problems is important because these may
      be treatable conditions for which survivors seek follow-up care and underscores
      the need for a multidisciplinary approach to survivor care.

PMID- 19841326
TI  - Outcome of patients treated for relapsed or refractory acute lymphoblastic
      leukemia: a Therapeutic Advances in Childhood Leukemia Consortium study.
AB  - PURPOSE: Despite improvements in treatment, approximately 20% of patients with
      acute lymphoblastic leukemia (ALL) experience relapse and do poorly. The
      Therapeutic Advances in Childhood Leukemia (TACL) Consortium was assembled to
      assess novel drugs for children with resistant leukemia. We hypothesize that
      novel agents and combinations that fail to improve baseline complete remission
      rates in comparable populations are unlikely to contribute to better outcomes and
      should be abandoned. We sought to define response rates and disease-free survival
      (DFS) rates in patients treated at TACL institutions, which could serve as a
      comparator for future studies. PATIENTS AND METHODS: We performed a retrospective
      cohort review of patients with relapsed and refractory ALL previously treated at
      TACL institutions between the years of 1995 and 2004. Data regarding initial and
      relapsed disease characteristics, disease response, and survival were collected
      and compared with those of published reports. RESULTS: Complete remission (CR)
      rates (mean +/- SE) were 83% +/- 4% for early first marrow relapse, 93% +/- 3%
      for late first marrow relapse, 44% +/- 5% for second marrow relapse, and 27% +/-
      6% for third marrow relapse. Five-year DFS rates in CR2 and CR3 were 27% +/- 4%
      and 15% +/- 7% respectively. CONCLUSION: We generally confirm a 40% CR rate for
      second and subsequent relapse, but our remission rate for early first relapse
      seems better than that reported in the literature (83% v approximately 70%). Our
      data may allow useful modeling of an expected remission rate for any population
      of patients who experience relapse.

PMID- 19841327
TI  - Feasibility trial of letrozole in combination with bevacizumab in patients with
      metastatic breast cancer.
AB  - PURPOSE: Preclinical models suggest that the use of anti-vascular endothelial
      growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the
      development of endocrine therapy resistance. We therefore performed a feasibility
      study to evaluate the safety of letrozole plus bevacizumab in patients with
      hormone receptor-positive metastatic breast cancer (MBC). METHODS: Patients with
      locally advanced breast cancer or MBC were treated with the aromatase inhibitor
      (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15
      mg/kg intravenously every 3 weeks). The primary end point was safety, defined by
      grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria,
      version 3.0. Secondary end points included response rate, clinical benefit rate,
      and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were
      permitted in the absence of progressive disease. RESULTS: Forty-three patients
      were treated. After a median of 13 cycles (range, 1 to 71 cycles), select
      treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19%
      and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades
      2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint
      pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at
      least stable disease on an NSAI, confounding efficacy results. Partial responses
      were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%.
      Median PFS was 17.1 months. CONCLUSION: Combination letrozole and bevacizumab was
      feasible with expected bevacizumab-related events of hypertension, headache, and
      proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus
      bevacizumab are in progress (Cancer and Leukemia Group B 40503).

PMID- 19841328
TI  - Clinically driven diagnostic antifungal approach in neutropenic patients: a
      prospective feasibility study.
AB  - PURPOSE: Preemptive strategies in neutropenic patients based on serum
      galactomannan (GM) -guided triggering of diagnostic work-up may be time-consuming
      and expensive when applied to the entire population. We have assessed the
      feasibility of a clinically driven diagnostic strategy without GM screening.
      PATIENTS AND METHODS: Patients with neutropenic fever underwent a baseline
      diagnostic work-up (BDWU; three blood cultures and other examinations as
      indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed
      tomography and other examinations as indicated) was reserved for patients with 4
      days of persisting or relapsing fever or with other clinical findings possibly
      related to an invasive fungal diseaser (IFD). Antifungal therapy was administered
      to patients diagnosed with IFD and empirically (negative IDWU) only to those with
      persisting neutropenic fever and worsening clinical conditions. RESULTS: Of 220
      neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases.
      Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes
      (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one
      patient with zygomycosis died without treatment. Only one patient received
      empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4
      mean blood samples per neutropenia episode were tested for GM. Our strategy
      allowed a 43% reduction in antifungal treatments compared with a standard
      empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and
      no undetected IFDs were found. CONCLUSION: A clinically driven diagnostic
      approach in selected neutropenia episodes offered effective antifungal control
      and reduced the exposure to unnecessary antifungal treatment.

PMID- 19841329
TI  - Preventing future cancers by testing women with ovarian cancer for BRCA
      mutations.
AB  - PURPOSE: Women with ovarian cancer have a 10% probability of carrying a BRCA
      mutation. If a mutation is identified, unaffected family members can undergo
      genetic testing and cancer risk-reducing strategies. We estimated the net health
      benefits and cost-effectiveness of different criteria for BRCA mutation testing
      in women with ovarian cancer, and the downstream benefits for their first-degree
      relatives (FDRs). METHODS: We developed a Markov Monte Carlo simulation model to
      compare four criteria for BRCA testing in women with ovarian cancer: no testing
      (reference); only if personal history of breast cancer, family history of
      breast/ovarian cancer, or Ashkenazi Jewish ancestry; only if invasive serous
      cancer; any invasive nonmucinous epithelial cancer. Net health benefit was life
      expectancy for FDRs and primary outcome was the incremental cost-effectiveness
      ratio (ICER). The model estimated the number of future breast and ovarian cancer
      cases in FDRs. RESULTS: BRCA testing based on personal/family history and
      ancestry could prevent future cases in FDRs with an ICER of $32,018 per year of
      life (LY) gained compared with the reference strategy. BRCA testing based on
      serous or any nonmucinous epithelial ovarian cancer could prevent more cancer
      cases, but at ICERs of $128,465 and $148,363 per LY gained, respectively.
      CONCLUSION: BRCA testing of women with ovarian cancer based on personal/family
      history of cancer or Ashkenazi Jewish ancestry is a cost-effective strategy to
      prevent future breast and ovarian cancers among FDRs. More inclusive testing
      strategies prevent additional cancer cases but at significant cost.

PMID- 19841331
TI  - Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach
      to improving therapeutic outcomes.
AB  - Chemotherapy dosing of the fluoropyrimidine 5-fluorouracil (5-FU) is currently
      based on body surface area. However, body surface area-based dosing has been
      associated with clinically significant pharmacokinetic variability, and as such,
      dosing based on body surface area may be of limited use. The clinical activity of
      5-FU is modest at standard doses, and in general, dosing is limited by the safety
      profile, with myelosuppression and gastrointestinal toxicity being the most
      commonly observed side effects. Various strategies have been developed to enhance
      the clinical activity of 5-FU, such as biochemical modulation, alterations in
      scheduling of administration, and the use of oral chemotherapy. Studies that have
      shown an association between plasma concentration with toxicity and clinical
      efficacy have shown that pharmacokinetically guided dose adjustments can
      substantially improve the therapeutic index of 5-FU treatment. These studies have
      shown that only 20%-30% of patients treated with a 5-FU-based regimen have 5-FU
      levels that are in the appropriate therapeutic range--approximately 40%-60% of
      patients are underdosed and 10%-20% of patients are overdosed. To date, 5-FU drug
      testing has not been widely used because of the lack of a simple, fast, and
      inexpensive method. Recent advances in testing based on liquid chromatography
      mass spectroscopy and a nanoparticle antibody-based immunoassay for 5-FU may now
      allow for routine monitoring of 5-FU in clinical practice. We review the data on
      pharmacokinetically guided dose adjustment of 5-FU and discuss the potential of
      this approach to advance therapeutic outcomes.

PMID- 19841332
TI  - Impact of tonsillectomy with or without adenoidectomy on the acoustic parameters
      of the voice: a comparative study.
AB  - OBJECTIVE: To assess the effects of chronic tonsillitis with or without
      adenoiditis and the effects of tonsillectomy with or without adenoidectomy on the
      voice by means of acoustic analysis. DESIGN: Prospective case-control study.
      SETTING: Yenepoya Medical College Hospital, a tertiary referral hospital.
      PATIENTS: Patients 5 to 26 years old with chronic tonsillitis with or without
      adenoiditis. INTERVENTIONS: Tonsillectomies were performed under general
      anesthesia by surgeons using cold steel instruments via a standard capsular
      dissection technique, and adenoids were removed by curettage. MAIN OUTCOME
      MEASURES: Acoustic analysis of 6 parameters (fundamental frequency, jitter,
      shimmer, harmonics: noise ratio, long-term average spectrum, and nasalance) 4
      weeks after surgery compared with 1 day before surgery. RESULTS: Postoperatively,
      shimmer altered in males, and hypernasality was eliminated in almost all cases.
      None of the other associations were significant statistically. CONCLUSIONS:
      Chronic tonsillitis and tonsillar hypertrophy cause alterations in some acoustic
      measurements, which make the voice dysharmonic and harsh. Tonsillectomy
      eliminates nasalance and lowers shimmer. Overall, it does not significantly alter
      dysphonia owing to disease.

PMID- 19841330
TI  - Randomized phase III trial on gemcitabine versus mytomicin in recurrent
      superficial bladder cancer: evaluation of efficacy and tolerance.
AB  - PURPOSE: Approximately 30% to 40% patients with a superficial bladder cancer
      treated with Bacille Calmette-Guerin (BCG) or epirubicin do not respond; of the
      initial responders, 35% have a relapse within 5 years. We compare the therapeutic
      efficacy and toxicity of intravescical infusions of gemcitabine (GEM) with
      mitomycin (MMC) in patients with a recurrent superficial bladder cancer. PATIENTS
      AND METHODS: Patients with a history of a previously treated, recurrent Ta-T1, G1
      G3 bladder transitional cell carcinoma were enrolled in the study. The patients
      received a 6-week course of GEM infusions or 4-week course of MMC. In both arms,
      for the initial responders who remained free of recurrences, maintenance therapy
      consisted of 10 monthly treatments during the first year. RESULTS: A total of 120
      patients were enrolled and randomly assigned to either the MMC or GEM treatment
      arm. At the end of the study, 109 patients (55 in MMC and 54 in GEM) were
      assessable. The median duration of follow-up was 36 months for either arm. In the
      GEM arm, 39 (72%) of 54 patients remained free of recurrence versus 33 (61%) of
      55 in MMC arm. Among patients with recurrences, 10 in the MMC arm and six in the
      GEM arm also had a progressive disease by stage. The incidence of chemical
      cystitis in the MMC arm was statistically higher than in the GEM arm (P = .012).
      CONCLUSION: This study demonstrates that GEM has better efficacy and lower
      toxicity than MMC; therefore, GEM appears as a logical candidate for intrabladder
      therapy in patients with refractory transitional cancer.

PMID- 19841333
TI  - Influence of single-trial results on clinical practice: example of
      adenotonsillectomy in children.
AB  - OBJECTIVE: To establish whether the results of a 2004 trial on the effectiveness
      of adenotonsillectomy in children with mild to moderate symptoms of throat
      infection or adenotonsillar hypertrophy affected physicians' beliefs about the
      benefits of the operation and influenced clinical practice. DESIGN: Prospective
      prior-posterior study. SETTING: Academic research. PARTICIPANTS: We evaluated
      beliefs prior and posterior to the 2004 trial regarding the benefits of
      adenotonsillectomy in a random sample of 120 Dutch otolaryngologists and 120
      Dutch general practitioners. MAIN OUTCOME MEASURE: Physicians were asked to give
      their estimates of the probability of recovery during 1 year after
      adenotonsillectomy or a nonsurgical strategy in 3 scenarios of children aged 3 to
      4 years with recurrent throat infection, upper respiratory tract infection (with
      or without fever), or sleep-related breathing disorder. RESULTS: Ninety-four
      percent of otolaryngologists (n = 46) and 31% of general practitioners (n = 14)
      were familiar with the 2004 trial results. Posterior beliefs of otolaryngologists
      and general practitioners did not differ substantially from prior beliefs;
      overall expectations regarding the benefits of adenotonsillectomy remained high.
      CONCLUSION: Dissemination of the 2004 trial results did not seem to affect the
      beliefs of physicians regarding the benefits of adenotonsillectomy. TRIAL
      REGISTRATION: isrctn.org Identifier: ISRCTN04973569.

PMID- 19841334
TI  - Microcystic lymphatic malformations of the tongue: diagnosis, classification, and
      treatment.
AB  - OBJECTIVE: To describe a classification of microcystic lymphatic malformations of
      the tongue and to investigate different treatment methods. DESIGN: Retrospective
      review of patients treated for microcystic lymphatic malformations of the tongue.
      Lymphatic malformations were classified into the following 4 groups according to
      their extent: isolated superficial microcystic lymphatic malformations of the
      tongue (stage I); isolated lymphatic malformations of the tongue with muscle
      involvement (stage II; stage IIA, involving a part of the tongue; stage IIB,
      involving the entire tongue); microcystic lymphatic malformations of the tongue
      and the floor of mouth (stage III); and extensive microcystic lymphatic
      malformations involving the tongue, floor of mouth, and further cervical
      structures (stage IV). PATIENTS: Twenty patients with microcystic lymphatic
      malformation of the tongue. MAIN OUTCOME MEASURES: Medical records were reviewed
      for demographic data and extent and treatment of the lymphatic malformations.
      RESULTS: Three patients had stage I disease; 5 patients, stage II; 3 patients,
      stage III; and 9 patients, stage IV. In 6 patients, the lymphatic malformations
      could be completely removed by carbon dioxide laser surgery; the remaining 13
      patients had persistent disease. CONCLUSIONS: The initial stage seems to predict
      outcome. Carbon dioxide laser therapy provides good results primarily in stages I
      and IIA lymphatic malformations. In advanced lymphatic malformations (stages IIB,
      III, and IV), an interdisciplinary approach is necessary, because complete
      surgical excision is often impossible owing to the diffuse growth behavior, and
      therefore recurrence and persistence are common.

PMID- 19841335
TI  - Duration-related efficacy of postoperative antibiotics following pediatric
      tonsillectomy: a prospective, randomized, placebo-controlled trial.
AB  - OBJECTIVE: To determine whether a 3-day course of postoperative antibiotics is as
      effective as a 7-day course in reducing pain and reducing time to resumption of a
      normal diet and level of activity following pediatric tonsillectomy. DESIGN: A
      prospective, randomized, placebo-controlled trial. SETTING: Academic medical
      center. PATIENTS: Forty-nine patients were enrolled in the study. Preoperative
      demographic information was obtained. INTERVENTIONS: Tonsillectomy with or
      without adenoidectomy was performed by the senior author (J.J.) using
      electrocautery. Patients were randomized to receive either a 3- or 7-day course
      of amoxicillin. MAIN OUTCOME MEASURES: Parents were asked to record the following
      information: analgesic use for the first 7 postoperative days, postoperative days
      the child initiated his or her usual diet and level of activity, and medical
      treatment for oral hemorrhage or dehydration. RESULTS: Of the 49 patients, 26
      were randomized to receive 7 days of postoperative antibiotics (group A) and 23
      to receive 3 days of antibiotics, followed by 4 days of placebo (group B).
      Results were obtained for 47 of the enrolled patients (96%). No statistically
      significant difference was noted between the 2 groups with regard to
      postoperative pain or time to resumption of a normal diet and level of activity.
      CONCLUSION: A 3-day course of antibiotics following pediatric tonsillectomy is as
      effective as a 7-day course with regard to postoperative analgesic use and
      resumption of normal diet and level of activity. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00662987.

PMID- 19841336
TI  - Clinical implication of the olfactory cleft in patients with chronic
      rhinosinusitis and olfactory loss.
AB  - OBJECTIVE: To evaluate the relationship between findings via osteomeatal unit
      computed tomography (OMU CT) of the olfactory cleft and olfactory function in
      patients with chronic rhinosinusitis (CRS). DESIGN: Retrospective review of
      medical records. SETTING: Referral center. PARTICIPANTS: Two hundred ten patients
      with CRS who underwent OMU CT and olfactory function tests were included in this
      study. MAIN OUTCOME MEASURES: All the paranasal sinuses were graded via the Lund
      Mackay scoring system. The olfactory cleft was graded on a scale of 0 to 4
      according to its opacification. Olfactory function was evaluated by the butanol
      threshold test (BTT) and the 16-odor identification test (OIT). RESULTS: The
      radiologic grade of the olfactory cleft was more significantly correlated with
      olfactory function than the grades of the paranasal sinuses. In patients without
      allergy, the BTT and OIT scores were inversely correlated with the CT score of
      the olfactory cleft. However, in patients with allergy, only the BTT score had a
      negative correlation with the CT score of the olfactory cleft, whereas the OIT
      score did not. The OIT score showed a significant negative correlation with the
      opacification of the olfactory cleft in the mild and moderate CRS group only,
      whereas the BTT score showed a significant negative correlation in all stages of
      CRS. CONCLUSIONS: The opacification of the olfactory cleft had a negative
      correlation with the olfactory function scores in patients with CRS. The
      olfactory cleft findings on OMU CT may give some clues to the olfactory function
      in patients with CRS.

PMID- 19841337
TI  - Relative hypotension and image guidance: tools for training in sinus surgery.
AB  - OBJECTIVES: To quantify the safety and efficiency of Postgraduate-Year II head
      and-neck-surgery residents who perform endoscopic sinus surgery, to observe any
      changes that accompanied accrued experience, and to measure and correlate blood
      loss and temporal efficiency with anesthesia-induced relative hypotension.
      DESIGN: Retrospective study. SETTING: University of California, San Diego,
      Medical Center. PATIENTS: One hundred two patients with chronic rhinosinusitis
      operated on between July 1, 2005, and June 30, 2006, by 3 Postgraduate-Year II
      head-and-neck-surgery residents. INTERVENTION: Endoscopic sinus surgery. MAIN
      OUTCOME MEASURES: Operative times, blood loss, case complexity, and anesthetic
      components were recorded and analyzed. RESULTS: One hundred two patients with
      chronic rhinosinusitis with and without polyposis received operative management.
      Mean operative time, with the inclusion of injection (10 minutes) and image
      guidance setup (5 minutes), was 77 minutes. Estimated blood loss averaged 42 mL
      for patients with chronic rhinosinusitis and 58 mL for patients with chronic
      rhinosinusitis and nasal polyps. The mean intraoperative blood pressure was
      101/65 mm Hg. No major complications occurred. CONCLUSIONS: Endoscopic sinus
      surgery may be safely performed by Postgraduate-Year II head-and-neck-surgery
      residents by means of hypotensive anesthesia techniques and image guidance.
      Outcome analysis demonstrates minimal blood loss, efficient operative times, and
      no significant complications.

PMID- 19841338
TI  - Treatment of postviral olfactory loss with glucocorticoids, Ginkgo biloba, and
      mometasone nasal spray.
AB  - OBJECTIVE: To analyze the efficacy of treating postviral olfactory loss with
      glucocorticoids, Ginkgo biloba, and mometasone furoate nasal spray. DESIGN:
      Randomized trial. SETTING: Academic research. PATIENTS: Seventy-one patients who
      were diagnosed as having postviral olfactory loss. MAIN OUTCOME MEASURES: All
      patients underwent olfactory function tests, including the butanol threshold test
      (BTT) and the cross-cultural smell identification test (CCSIT), and follow-up
      tests were performed 4 weeks later. In the interim, 28 patients were treated with
      prednisolone for 2 weeks (monotherapy), and the other 43 patients were treated
      with prednisolone for 2 weeks plus G biloba for 4 weeks (combination therapy).
      All patients used mometasone nasal spray twice daily for 4 weeks. RESULTS: Scores
      on the BTT and CCSIT significantly increased after treatment in both groups (P <
      .001 for both). The mean (SD) BTT score changes were 1.4 (2.2) in the monotherapy
      group and 2.2 (2.9) in the combination therapy group (P = .22). The mean (SD)
      CCSIT score changes were 0.9 (1.7) in the monotherapy group and 1.9 (2.7) in the
      combination therapy group (P = .11). On the BTT, the treatment response (defined
      as a score increase of > or =3) rates were 32% (9 of 28) in the monotherapy group
      and 37% (16 of 43) in the combination therapy group (P = .66), and the odds ratio
      was 1.25 (95% confidence interval, 0.46-3.42). On the CCSIT, the treatment
      response rates were 14% (4 of 28) in the monotherapy group and 33% (14 of 43) in
      the combination therapy group (P = .08), and the odds ratio was 2.89 (95%
      confidence interval, 0.84-9.97). CONCLUSIONS: Olfactory function in patients with
      postviral olfactory loss was significantly improved by both treatment modalities.
      Although the treatment response was not statistically different between the
      monotherapy group and the combination therapy group, the addition of G biloba
      showed a tendency of greater efficacy in the treatment of postviral olfactory
      loss.

PMID- 19841339
TI  - The hemostatic and hemodynamic effects of epinephrine during endoscopic sinus
      surgery: a randomized clinical trial.
AB  - OBJECTIVE: To assess the hemodynamic and hemostatic effects of 2 different
      concentrations of epinephrine in local anesthetic used during functional
      endoscopic sinus surgery (FESS). Injection of local anesthetic containing
      epinephrine during endoscopic sinus surgery, while providing hemostasis, has been
      associated with cardiac adverse effects such as tachycardia, hypertension, as
      well as arrhythmias. DESIGN: Double-blind, randomized clinical trial. SETTING:
      Tertiary referral center. PATIENTS: A total of 140 patients undergoing FESS
      randomly divided into 2 groups, with group 1 receiving lidocaine hydrochloride,
      2%, with 1:100 000 epinephrine and group 2, lidocaine, 2%, with 1:200 000
      epinephrine. MAIN OUTCOME MEASURES: Baseline and postinjection hemodynamic
      parameters were recorded at 1-minute intervals for 5 minutes. Patient
      demographics, the extent of surgery, and the presence of polyps were recorded in
      both groups. Hemodynamic and hemostatic parameters and intraoperative blood loss
      were compared. RESULTS: Significant hemodynamic fluctuations were noted following
      injection of lidocaine, 2%, with 1:100 000 epinephrine (group 1). Increases in
      heart rate and systolic, diastolic, and mean arterial blood pressure were noted
      in group 1 patients. The increase was found to be significant (P < .001) in the
      first and second minutes after injection and decreased to baseline level by the
      fifth minute. This fluctuation was not noted in group 2 patients, who received
      lidocaine, 2%, with 1:200 000 epinephrine. Using a standardized scale to assess
      surgical bleeding, no statistical difference in the 2 groups was observed (P >
      .05). CONCLUSION: Submucosal injection of lidocaine, 2%, with 1:200 000
      epinephrine during FESS does not lead to hemodynamic fluctuations or increased
      intraoperative bleeding compared with lidocaine, 2%, with 1:100 000 epinephrine.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00852410.

PMID- 19841340
TI  - A new surgical method of dynamic nasal valve collapse.
AB  - OBJECTIVE: To describe a technique for internal nasal valve collapse using
      radiofrequency-induced thermotherapy (RFITT). DESIGN: Prospective study. SETTING:
      Academic research center. PATIENTS: A total of 28 patients with nasal obstruction
      due to inspiratory nasal valve collapse were included in this study.
      INTERVENTION: Radiofrequency-induced thermotherapy. MAIN OUTCOME MEASURES: Visual
      analog scale score. RESULTS: Severity of obstruction scores improved in all
      patients, with the mean score improving at the left nostril from 8.2 before
      treatment to 3.4 after treatment and at the right nostril from 8.9 before
      treatment to 4.1 after treatment. The outcomes were measured using visual analog
      scale score before treatment and at 16 weeks after treatment. Improvement was
      shown in severity of obstruction (P < .001). CONCLUSIONS: This new method appears
      to be safe, quick, bloodless, and painless. These good, encouraging preliminary
      results must be confirmed by further study and long-term follow-up.

PMID- 19841341
TI  - Decompression of the orbital apex: an alternate approach to surgical excision for
      radiographically benign orbital apex tumors.
AB  - OBJECTIVE: To study the outcome of patients with orbital apex lesions treated
      with endoscopic decompression alone. DESIGN: Retrospective medical chart review
      with a mean follow-up of 25.6 months. SETTING: Departments of Ophthalmology and
      Otolaryngology, University of Washington, Seattle. PATIENTS: Five individuals
      seen at the University of Washington Medical Center from November 2003 through
      December 2005 with visual disturbance caused by orbital apex lesions as
      documented by preoperative magnetic resonance imaging or computed tomographic
      scan. INTERVENTION: All patients underwent endoscopic decompression of the medial
      wall of the orbital apex with incision of the periorbita. MAIN OUTCOME MEASURES:
      Postoperative visual acuity, presence or absence of a relative afferent pupillary
      defect, color vision, and visual field were recorded. RESULTS: All 5 patients
      presented with visual field deficits, 4 of whom improved postoperatively. Three
      patients had dyschromatopsia preoperatively, 2 of whom improved postoperatively.
      Visual acuity improved or stabilized in 4 of 5 patients postoperatively. One
      patient had progressive visual loss during the course of her follow-up, which,
      after obtaining postoperative imaging, was attributed to inadequate decompression
      of the apex at its most posterior aspect. This same patient also developed
      postoperative sinusitis that resolved with antibiotic treatment. Two patients
      developed diplopia, 1 in primary gaze requiring treatment with prismatic lenses.
      All patients presented with and maintained normal intraocular pressures.
      CONCLUSION: Orbital apex lesions can often be effectively and relatively safely
      treated by endoscopic decompression alone.

PMID- 19841342
TI  - The role of pectoralis major muscle flap in salvage total laryngectomy.
AB  - OBJECTIVE: To assess the utility of the pectoralis major muscle flap (PMMF) in
      patients undergoing salvage total laryngectomy. DESIGN: Retrospective cohort
      analysis. SETTING: Tertiary care cancer center. PATIENTS: The study included 461
      patients who underwent laryngectomy. Eighty of them underwent salvage surgery
      with primary pharyngeal closure. INTERVENTIONS: Of the 80 patients, 69 (86%)
      underwent primary pharyngeal closure alone and 11 (14%) underwent a PMMF, which
      was used to buttress the pharyngeal suture line. MAIN OUTCOME MEASURE: Two
      hundred thirty-six variables were recorded for each patient. Complications
      related to pharyngeal closure were measured. RESULTS: Sixty-four percent of the
      patients who underwent PMMF also underwent chemoradiation therapy as the initial
      definitive treatment compared with 25% in the non-PMMF group (P = .03). On
      multivariate analysis, chemoradiation therapy was the only independent predictor
      of pharyngocutaneous fistula formation (relative risk, 1.82; P = .02).
      Nevertheless, the pharyngocutaneous fistula rate was similar in the PMMF (27%)
      and the non-PMMF (24%) groups. Furthermore, similar durations of tube feeding,
      days to oral feeding, and hospitalization period were recorded in both groups.
      CONCLUSION: The PMMF should be used judiciously as a surgical adjunct in high
      risk patients, with the goal of minimizing the risk for the development of a
      pharyngocutaneous fistula.

PMID- 19841343
TI  - Metastatic carcinoma of the neck of unknown primary origin: evolution and
      efficacy of the modern workup.
AB  - OBJECTIVE: To assess the efficacy of various diagnostic modalities in detecting
      occult primary tumor location. DESIGN: Retrospective medical record study.
      SETTING: Academic head and neck oncology practice. PATIENTS: A total of 183
      consecutive patients with metastatic carcinoma of the neck from an unknown
      primary tumor during a 10-year period, after exclusion of those with previous
      history of head and neck cancer, a primary tumor site evident on physical
      examination, or primary tumors of the neck. MAIN OUTCOME MEASURES: Identification
      of primary tumor location by various imaging modalities and panendoscopy with
      directed biopsies. RESULTS: Primary tumor location was identified in 84 patients
      (45.9%). Preoperative imaging (computed tomography [CT], magnetic resonance
      imaging, positron emission tomography [PET], and/or PET-CT fusion scan)
      identified sites suggestive of primary tumor location in 69 patients. Subsequent
      directed biopsy of these sites yielded positive results in 42 cases (60.9%). The
      rate of successful identification of a primary tumor for each of the imaging
      modalities was as follows: CT scan of the neck, 14 of 146 patients (9.6%);
      magnetic resonance imaging of the neck, 0 of 13 patients (0%); whole-body PET
      scan, 6 of 41 patients (14.6%); and PET-CT fusion study, 23 of 52 patients
      (44.2%) (P = .001). The highest yield in identifying primary tumor sites was
      obtained in patients who had undergone PET-CT plus panendoscopy with directed
      biopsies with or without tonsillectomy: 31 of 52 patients (59.6%). CONCLUSION:
      Diagnostic workup including PET-CT, alongside panendoscopy with directed biopsies
      including bilateral tonsillectomy, offers the greatest likelihood of successfully
      identifying occult primary tumor location.

PMID- 19841344
TI  - Salvage treatment of late neck metastasis in esthesioneuroblastoma: a meta
      analysis.
AB  - OBJECTIVE: Esthesioneuroblastoma (ENB) is an uncommon tumor of the sinonasal
      region with a 20% rate of neck metastases. To our knowledge, the rate of neck
      metastases occurring 6 or more months after diagnosis has not been well
      characterized. The rate of successful salvage of these late neck metastases,
      defined in this study as disease-free survival for at least 1 year, has not been
      previously reported. DESIGN: Meta-analysis examining 33 articles published since
      1990. PATIENTS: A total of 678 patients with ENB with 79 patients with neck
      metastases occurring 6 or more months after the initial diagnosis. INTERVENTIONS:
      Patients were grouped according to treatment with surgery, radiotherapy, or
      combined surgery and radiotherapy. MAIN OUTCOME MEASURES: The rate of successful
      salvage of late neck metastases, defined as disease-free survival for at least 1
      year, was compared for the 3 treatment groups. RESULTS: The rate of cervical
      metastases was 20.2%, with a 12.4% rate of late neck metastases. The combined
      successful salvage rate for late neck metastases with surgery, radiation, or
      combined therapy was 31.2%. An odds ratio (OR) analysis revealed that surgery
      plus radiation provided a statistically significant increase in the rate of
      successful salvage in patients with late neck metastases, with an OR of 8.6 vs
      single modality therapy and a number-needed-to-treat of 3. We found no difference
      in the OR for successful salvage for surgery alone vs radiation alone (OR, 1.5).
      CONCLUSION: Treatment of neck metastases occurring 6 or more months after an
      initial diagnosis of ENB with combined surgery and radiotherapy provides a
      statistically significant survival advantage vs single-modality therapy.

PMID- 19841345
TI  - Reduced gamma-catenin expression and poor survival in oral squamous cell
      carcinoma.
AB  - OBJECTIVE: To investigate whether reduced expression of alpha-, beta-, or gamma
      catenin predicts poor survival in oral squamous cell carcinoma (OSCC). DESIGN:
      Immunohistochemical analyses of a retrospective cohort. SETTING: University
      affiliated hospital. PATIENTS: One hundred twenty-four patients with OSCC. MAIN
      OUTCOME MEASURE: The prognostic value of gamma-catenin expression on disease
      specific survival in different T and N category groups in patients with OSCC.
      RESULTS: Reduced expression of gamma-catenin correlated with poor tumor
      differentiation of OSCC (P = .04). Patients with reduced gamma-catenin expression
      in the primary tumor had significantly more frequent lymph node metastasis than
      did patients with normal gamma-catenin expression (P = . 03). Reduced expression
      of gamma-catenin (004) but not of alpha-catenin (P = .25) or beta-catenin (P =
      .48) correlated with poor clinical outcome. Reduced gamma-catenin expression
      predicted poor disease-specific survival also in the 92 patients with T1 or T2
      tumors (P = . 02). In multivariate analysis, advanced T category (P = . 04), neck
      lymph node metastases (P = . 01), and reduced gamma-catenin expression (P = . 05)
      were independently related to poor survival. CONCLUSIONS: Reduced expression of
      gamma-catenin was associated with poor differentiation of OSCC, with neck lymph
      node metastases, and, more importantly, with poor disease-specific survival. Loss
      of gamma-catenin expression seems to contribute to metastatic properties of OSCC.
      Evaluation of the expression pattern of gamma-catenin may be useful for
      predicting outcome in patients with OSCC.

PMID- 19841346
TI  - Geriatric thyroidectomy: safety of thyroid surgery in an aging population.
AB  - OBJECTIVE: To ascertain whether there are incremental risks associated with
      thyroid surgery in the elderly population. DESIGN: Prospective analysis of a
      consecutive single-surgeon series of patients undergoing thyroid surgery at an
      academic health center. SETTING: Tertiary care health center. PATIENTS: The study
      included patients aged 21 to 35 years and patients 65 years and older who
      underwent thyroidectomy. MAIN OUTCOME MEASURES: Pathology reports, complications
      (including rates of temporary and permanent hypocalcemia and temporary and
      permanent true vocal fold [TVF] paralysis), and need for admission or readmission
      were included in the analysis. RESULTS: There were 86 youthful patients who
      underwent thyroidectomy between November 2003 and December of 2007; 44 elderly
      patients underwent surgery during that same time frame. There were no deaths in
      either cohort, no hematomas, and no cases of permanent TVF paralysis. The elderly
      patients had a similar rate of complications when compared with the youthful
      patients, including transient hypocalcemia (12.5% vs 11.1%, respectively) and
      temporary TVF paresis (2.9% vs 3.9%), but a higher rate of readmission (4.5% vs
      1.2%, P = .26). CONCLUSIONS: Thyroid surgeons will be faced more often with the
      prospect of elective thyroid surgery in patients of advanced age as an
      increasingly aged population emerges and the prevalence of thyroid nodules and
      thyroid cancer increases. Thyroid surgery in elderly patients is safe and no more
      dangerous than surgery in youthful patients. There is a slightly higher rate of
      readmission.

PMID- 19841347
TI  - Branchial cleft cyst causing carotid sinus syndrome.

PMID- 19841348
TI  - Narrow duplicated internal auditory canal: a rare inner ear malformation with
      sensorineural hearing loss.

PMID- 19841349
TI  - Radiology quiz case 1. Extracranial meningioma.

PMID- 19841350
TI  - Radiology quiz case 2. Shrimp tail foreign body.

PMID- 19841351
TI  - Pathology quiz case 1. Sino-orbital cystic echinococcosis (CE).

PMID- 19841352
TI  - Pathology quiz case 2. Rhabdomyoma, adult type.

PMID- 19841353
TI  - Use of a saline bag as a shoulder roll during surgery not recommended.

PMID- 19841354
TI  - Quantifying access to surgical care.

PMID- 19841355
TI  - Use of Seamguard to prevent pancreatic leak following distal pancreatectomy.
AB  - OBJECTIVE: To investigate the use of Seamguard, a bioabsorbable staple line
      reinforcement product, to prevent pancreatic leak after distal pancreatectomy.
      DESIGN, SETTING, AND PARTICIPANTS: A retrospective study examined 85 consecutive
      patients undergoing distal pancreatectomy at an academic institution from
      September 5, 1997, to September 30, 2007. MAIN OUTCOME MEASURES: Pancreatic
      fistula and overall mortality and morbidity. RESULTS: In February 2004, the use
      of Seamguard in distal pancreas resections was introduced at our institution.
      Indications for resection included trauma (11 patients), neoplasms (62 patients),
      and chronic pancreatitis (12 patients). Pancreatic leak was defined as drain
      output of 25 mL/d or more 7 days postoperatively with a drain amylase level of
      1000 U/L or more. Pancreatic leak occurred in 10 of 38 patients (26%) undergoing
      conventional resection with suture ligation of the pancreatic duct or
      nonreinforced stapled resection vs 2 of 47 patients (4%) undergoing staple
      resection using Seamguard reinforcement. Multivariate analysis showed that use of
      Seamguard with the stapler independently decreased the risk for pancreatic
      fistula after distal pancreatectomy (odds ratio, 0.07; 95% confidence interval,
      0.01-0.43; P = .01). CONCLUSIONS: The use of Seamguard is quickly becoming a
      common adjunct in distal pancreas resections. Our study shows a lower incidence
      of pancreatic leak after distal pancreatectomy with the use of this staple line
      reinforcing product.

PMID- 19841356
TI  - Ischemic colitis after endovascular aortoiliac aneurysm repair: a 10-year
      retrospective study.
AB  - OBJECTIVE: To examine the incidence, cause, and outcomes of ischemic colitis
      after endovascular stent graft repair of aortoiliac aneurysms (EVAR). DESIGN:
      Medical record review. SETTING: University teaching hospital. PATIENTS: Eight
      hundred nine patients treated during 10 years were included in the study.
      Preoperative data regarding the size of the aneurysm, hypogastric coil
      embolization, and inferior mesenteric artery patency were evaluated by means of
      computed tomographic scans and aortograms. Ischemic colitis was diagnosed by
      lower endoscopy or pathology reports. MAIN OUTCOME MEASURES: Ischemic colitis
      after EVAR. RESULTS: Eleven patients (1.4%) developed ischemic colitis. Seven
      patients' episode occurred less than 30 days from repair (early), whereas 4
      occurred 30 days or more from repair (late). Ten of 11 patients had preoperative
      inferior mesenteric artery occlusion. Microembolization was seen histologically
      in 2 patients in the early group, both of whom died. A significant increase in
      ischemic colitis was seen in patients undergoing preoperative unilateral
      hypogastric coil embolization (P = .02). Three of the patients with late ischemic
      colitis had comorbidities other than the EVAR to explain the ischemia.
      CONCLUSIONS: The incidence of ischemic colitis is decreased in patients
      undergoing EVAR vs open repair. The cause of the ischemia is multifactorial and
      seems to differ between patients in the early and late groups. Microembolization
      tends to produce severe ischemic colitis and is usually fatal. There should be a
      low threshold for performing endoscopy in any patient thought to have ischemic
      colitis after EVAR.

PMID- 19841357
TI  - Role of hepatitis B virus infection in the prognosis after hepatectomy for
      hepatocellular carcinoma in patients with cirrhosis: a Western dual-center
      experience.
AB  - HYPOTHESIS: The role of hepatitis B virus (HBV) infection in determining the
      prognosis after hepatectomy for hepatocellular carcinoma (HCC) in patients with
      cirrhosis is controversial. DESIGN: Retrospective study based on multicenter
      prospectively updated databases. SETTING: Two tertiary referral centers
      specializing in hepatobiliary surgery. PATIENTS: Two hundred four consecutive
      patients with cirrhosis undergoing hepatectomy for single nodules of HCC of 5 cm
      or smaller from January 1, 1997, through September 30, 2006. INTERVENTIONS:
      Patients were divided into the following groups according to their preoperative
      viral status: HBV positive and hepatitis C virus (HCV) negative (group 1); HBV
      negative and HCV positive (group 2); HBV negative and HCV negative (group 3); and
      HBV positive and HCV positive (group 4). MAIN OUTCOME MEASURES: A multivariate
      analysis was performed to determine factors associated with recurrence-free
      survival (RFS) among demographic, clinical, pathological, and surgical variables.
      RESULTS: The 2 centers had comparable RFS and early and late recurrence rates.
      Five-year RFS was significantly higher in groups 2 and 3 compared with group 1
      (38%, 34%, and 9%, respectively; P = .007 and P = .05). Factors independently
      associated with RFS were HBV infection (P = .009; odds ratio, 1.79; 95%
      confidence interval, 1.15-2.78) and poor tumor differentiation (P < .001; odds
      ratio, 2.01; 95% confidence interval, 1.36-2.96). The concomitance of 0, 1, or 2
      risk factors led to 5-year RFS rates of 49%, 20%, and 8%, respectively (P <
      .001). CONCLUSIONS: Infection with HBV is a strong predictive factor for lower
      RFS after hepatectomy for a single nodule of HCC of 5 cm or smaller in patients
      with cirrhosis, providing a further basis for adjuvant antiviral treatment.
      Patients who are seropositive for HBV with poorly differentiated HCC should also
      be considered to be at a high risk of recurrence and possibly included in a
      policy of salvage liver transplantation.

PMID- 19841358
TI  - Predictors of long-term mortality after bariatric surgery performed in Veterans
      Affairs medical centers.
AB  - HYPOTHESIS: The purpose of this study was to examine patient factors associated
      with mortality among veterans who undergo bariatric surgery. DESIGN: Prospective
      study that uses data from the Veterans Affairs (VA) National Surgical Quality
      Improvement Program. SETTING: Group Health Center for Health Studies, the VA
      North Texas Health Care System, the Denver VA Medical Center, and the Durham VA
      Medical Center. PATIENTS: We identified 856 veterans who had undergone bariatric
      surgery in 1 of 12 VA bariatric centers from January 1, 2000, through December
      31, 2006. MAIN OUTCOME MEASURES: The risk of death was estimated via Cox
      proportional hazards. RESULTS: The 856 veterans had a mean body mass index (BMI)
      of 48.7, a mean age of 54 years, and a mean DCG score of 0.76; 73.0% were men,
      83.9% were white, and 7.0% had an ASA class equal to 4. Fifty-four veterans
      (6.3%) had died by the end of 2006. In our Cox models, patients with a BMI
      greater than 50 (superobesity; hazard ratio [HR], 1.8; P = .04) or a DCG score
      greater than or equal to 2 (HR, 3.4; P < .001) had an increased risk of death.
      CONCLUSION: Superobese veterans and those with a greater burden of chronic
      disease had a greater risk of death after bariatric surgery from 2000 through
      2006.

PMID- 19841359
TI  - Late results of the surgical treatment of 125 patients with short-segment Barrett
      esophagus.
AB  - HYPOTHESIS: The results of surgical treatment of patients with long-segment
      Barrett esophagus (BE) have been extensively reported. However, few publications
      refer to the results of surgery 5 years after the fact among patients with short
      segment BE. This study aimed to determine the late results of 3 surgical
      procedures in patients with short-segment BE by subjective and objective
      measurements. DESIGN: Prospective, nonrandomized study starting on March 1, 1987,
      and ending on December 31, 2005. SETTING: A prospective, descriptive study of a
      group of patients. PATIENTS: A total of 125 patients with short-segment BE
      underwent 3 operations in different periods: duodenal switch plus highly
      selective vagotomy and antireflux technique in 31 patients, vagotomy plus partial
      gastrectomy and Roux-en-Y loop with antireflux surgery in 58 patients, and
      laparoscopic Nissen fundoplication in 36 patients. MAIN OUTCOME MEASURES: Late
      subjective and objective outcomes of the 3 different surgical procedures.
      RESULTS: No operative mortality and only 2 postoperative complications (1.6%)
      occurred. The regression from intestinal metaplasia to cardiac or oxyntocardiac
      mucosa occurred in 60.8% to 65.4% of the patients, at a mean time of 39 to 56
      months after surgery. Visick grading showed Visick grade I or II in 86.3% to
      100.0% of the patients. No progression to low- or high-grade dysplasia or
      adenocarcinoma occurred. CONCLUSIONS: On the basis of these results, laparoscopic
      Nissen fundoplication seems to be the surgical option for patients with short
      segment BE because it is less invasive, has fewer side effects, and produces good
      results in the long-term follow-up.

PMID- 19841360
TI  - Pulmonary embolism and deep venous thrombosis in trauma: are they related?
AB  - HYPOTHESIS: Pulmonary embolism (PE) and deep venous thrombosis (DVT) in trauma
      are related. DESIGN: Retrospective review of medical records. SETTING: Academic
      level I trauma center. PATIENTS: Trauma patients who underwent computed
      tomographic pulmonary angiography (CTPA) with computed tomographic venography
      (CTV) of the pelvic and proximal lower extremity veins over a 3-year period
      (January 1, 2004, to December 31, 2006) were reviewed. Data on demographics,
      injury type and severity, imaging findings, hospital length of stay, and
      mortality were collected. MAIN OUTCOME MEASURES: Pulmonary embolism and DVT.
      RESULTS: Among 247 trauma patients undergoing CTPA/CTV, PE was diagnosed in 46
      (19%) and DVT in 18 (7%). Eighteen PEs were central (main or lobar pulmonary
      arteries), and 28 PEs were peripheral (segmental or subsegmental branches).
      Pulmonary embolism occurred within the first week of injury in two-thirds of
      patients. Seven patients with PE (4 femoral, 2 popliteal, and 1 iliac) had DVT.
      Pulmonary embolism was central in 5 patients and peripheral in 2 patients. No
      significant differences were noted in any of the examined variables between
      patients with PE having DVT and those not having DVT. CONCLUSIONS: Few patients
      with PE have DVT of the pelvic or proximal lower extremity veins. Pulmonary
      embolism may not originate from these veins, as commonly believed, but instead
      may occur de novo in the lungs. These findings have implications for
      thromboprophylaxis and, particularly, the value of vena cava filters.

PMID- 19841361
TI  - Continuous postoperative blood glucose monitoring and control by artificial
      pancreas in patients having pancreatic resection: a prospective randomized
      clinical trial.
AB  - OBJECTIVE: To evaluate a closed-loop system providing continuous monitoring and
      strict control of perioperative blood glucose following pancreatic resection.
      DESIGN: Prospective, randomized clinical trial. PATIENTS: Thirty patients who had
      pancreatic resection for pancreatic neoplasm. INTERVENTIONS: Patients were
      prospectively randomized. Perioperative blood glucose levels were continuously
      monitored using an artificial endocrine pancreas (STG-22). Glucose levels were
      controlled using either the sliding scale method (sliding scale group, n = 13) or
      the artificial pancreas (artificial pancreas group, n = 17). MAIN OUTCOME
      MEASURES: Incidence of severe hypoglycemia (<40 mg/dL) during the intensive care
      period following pancreatic resection in patients monitored with the artificial
      pancreas. The secondary outcome measure was the total amount of insulin required
      for glycemic control in the first 18 hours after pancreatic resection in each
      patient group. RESULTS: In the sliding scale group, postoperative blood glucose
      levels rose initially before reaching a plateau of approximately 200 mg/dL
      between 4 and 6 hours after pancreatectomy. The levels remained high for 18 hours
      postoperatively. In the artificial pancreas group, blood glucose levels reduced
      steadily, reaching the target zone (80-110 mg/dL) by 6 hours after surgery. The
      total insulin dose administered per patient during the first postoperative 18
      hours was significantly higher in the artificial pancreas group (mean [SD], 107
      [109] IU) than the sliding scale group (8 [6] IU; P < .01). Neither group showed
      hypoglycemia. CONCLUSIONS: Perioperative use of an artificial endocrine pancreas
      to control pancreatogenic diabetes after pancreatic resection is an easy and
      effective way to maintain near-normal blood glucose levels. The artificial
      pancreas shows promise for use as insulin treatment for patients with
      pancreatogenic diabetes after pancreatic resection.

PMID- 19841362
TI  - Statin use and the risk of surgical site infections in elderly patients
      undergoing elective surgery.
AB  - OBJECTIVE: To examine whether preoperative statin use is associated with a
      reduced risk of surgical site infections. DESIGN, SETTING, AND PATIENTS:
      Population-based retrospective cohort study of all elderly patients undergoing
      elective surgery in Ontario from April 1, 1992, through March 31, 2006.
      Preoperative statin use was identified using provincewide pharmacy records.
      Procedure and patient characteristics were derived from hospital and physician
      claims databases within Canada's single-payer universal health care system. MAIN
      OUTCOME MEASURE: The 30-day risk of surgical site infection was derived from the
      initial admission, outpatient consultations, and hospital readmissions. RESULTS:
      The cohort included 469,349 distinct elderly patients undergoing elective
      surgery, of whom 68,387 (14.6%) were statin users. The primary analysis included
      53,565 statin users matched to 53,565 statin nonusers undergoing the same
      procedure in the same hospital by the same surgeon. Unadjusted analysis revealed
      a slight increase in the risk of surgical site infection among statin users
      compared with nonusers (8.9% vs 8.7%; P < .001), which disappeared after
      adjustment for demographics, health care utilization variables, comorbidities,
      and concurrent medication therapy (odds ratio, 1.00; 95% confidence interval,
      0.95-1.04; P = .85). A similar lack of association was seen when matching was
      extended to include propensity scores (odds ratio, 0.99; 95% confidence interval,
      0.94-1.05; P = .82). The lack of association persisted across pharmacologic,
      patient, and procedure subgroups. CONCLUSIONS: Statin use is not associated with
      an altered risk of surgical site infection. Prevention efforts should be directed
      toward other evidence-based strategies.

PMID- 19841363
TI  - Management and treatment of iliopsoas abscess.
AB  - HYPOTHESIS: Even with improved diagnostic modalities, the optimum management
      strategy for iliopsoas abscess (IPA) is not uniform, and a better understanding
      of treatment options is needed. DESIGN: Retrospective case series. SETTING:
      Academic center. PATIENTS: Sixty-one consecutive patients diagnosed as having IPA
      at the Mount Sinai Medical Center, New York, New York, from August 1, 2000, to
      December 30, 2007. MAIN OUTCOME MEASURES: Development and cause of IPA, the need
      for additional interventions, morbidity, and mortality. RESULTS: The mean age of
      the patients was 53 years. Most patients were initially seen with pain (95% [58
      of 61]), gastrointestinal tract complaints (43% [26 of 61]), and lower extremity
      pain (30% [18 of 61]). Primary and secondary abscesses occurred in 11% (7 of 61)
      and 89% (54 of 61), respectively. The most frequent underlying cause of secondary
      abscesses was inflammatory bowel disease. Broad-spectrum antibiotics were
      prescribed in all patients. Computed tomography was the most common diagnostic
      modality used. Abscesses were larger than 6 cm in 39% of patients (24 of 61),
      bilateral in 13% (8 of 61), and multiple in 25% (15 of 61). Nine patients were
      treated using antibiotics alone, with a success rate of 78% (7 of 9). Forty-eight
      patients initially underwent percutaneous drainage, which was successful in 40%
      (19 of 48). Among those with unresolved IPAs, 71% of patients ultimately required
      surgery, and the IPAs were typically associated with underlying gastrointestinal
      tract causes. Seven percent (4 of 61) of patients directly underwent exploratory
      surgery and drainage, and all of these interventions were successful. The overall
      mortality was 5% (3 of 61). CONCLUSIONS: Iliopsoas abscess remains a therapeutic
      challenge. Gastrointestinal tract disease is the most common cause, with computed
      tomography as the diagnostic modality of choice. Percutaneous drainage remains
      the initial treatment modality but is rarely the sole therapy required. Patients
      with inflammatory bowel disease are likely to require ultimate operative
      management.

PMID- 19841364
TI  - Establishing standards of quality for elderly patients undergoing pancreatic
      resection.
AB  - OBJECTIVE: To evaluate pancreatic surgery as a model for high-acuity surgery in
      elderly patients for immediate and long-term outcomes, predictors of adverse
      outcomes, and hospital costs. DESIGN: Retrospective case series. SETTING:
      University tertiary care referral center. PATIENTS: Four hundred twelve
      consecutive patients who underwent pancreatic resection from October 1, 2001,
      through March 31, 2008, for benign and malignant periampullary conditions. MAIN
      OUTCOME MEASURES: Clinical outcomes were compared for elderly (> or = 75 years)
      and nonelderly patient cohorts. Quality assessment analyses were performed to
      show the differential impact of complications and resource utilization between
      the groups. RESULTS: The elderly cohort constituted one-fifth of all patients.
      Benchmark standards of quality were achieved in this group, including low
      operative mortality (1%). Despite higher patient acuity, clinical outcomes were
      comparable to those of nonelderly patients at a marginal cost increase (median,
      $2202 per case). Cost modeling analysis showed further that minor and moderate
      complications were more frequent but no more debilitating for elderly patients.
      Major complications, however, were far more threatening to older patients. In
      these cases, duration of hospital stay doubled, and invasive interventions were
      more commonly deployed. CONCLUSIONS: Quality standards for pancreatic resection
      in the elderly can--and should--mirror those for younger patients. Age-related
      care, including geriatric consultation, supplemental enteral nutrition, and early
      rehabilitation placement planning, can be designed to mitigate the impact of
      complications in the elderly and guarantee quality.

PMID- 19841365
TI  - Transumbilical laparoscopic cholecystectomy: a novel technique.
AB  - OBJECTIVE: To describe a novel technique for performing laparoscopic
      cholecystectomies using no proprietary or specially designed equipment, while
      still minimizing the incision and leaving a nearly invisible scar. DESIGN:
      Retrospective review. SETTING: Community teaching hospital. PATIENTS: Twelve
      patients having uncomplicated laparoscopic cholecystectomy. MAIN OUTCOME
      MEASURES: Number and appearance of postoperative scars. RESULTS: Twelve attempts
      to perform the procedure with our new technique were completed successfully. None
      of the patients required conversion to the standard technique, which requires
      additional ports. All of the patients were pleased with their results. No
      identifiable mark was visible in the right upper quadrant of any of the patients;
      at the 2-week follow-up, the umbilical incisions were nearly invisible, even to
      the patients. CONCLUSION: This novel technique can be performed safely and
      effectively while minimizing the number and extent of incisions.

PMID- 19841366
TI  - Consensus review of optimal perioperative care in colorectal surgery: Enhanced
      Recovery After Surgery (ERAS) Group recommendations.
AB  - OBJECTIVES: To describe a consensus review of optimal perioperative care in
      colorectal surgery and to provide consensus recommendations for each item of an
      evidence-based protocol for optimal perioperative care. DATA SOURCES: For every
      item of the perioperative treatment pathway, available English-language
      literature has been examined. STUDY SELECTION: Particular attention was paid to
      meta-analyses, randomized controlled trials, and systematic reviews. DATA
      EXTRACTION: A consensus recommendation for each protocol item was reached after
      critical appraisal of the literature by the group. DATA SYNTHESIS: For most
      protocol items, recommendations are based on good-quality trials or meta-analyses
      of such trials. CONCLUSIONS: The Enhanced Recovery After Surgery (ERAS) Group
      presents a comprehensive evidence-based consensus review of perioperative care
      for colorectal surgery. It is based on the evidence available for each element of
      the multimodal perioperative care pathway.

PMID- 19841367
TI  - Simultaneous bicavitary hyperthermic chemoperfusion in the management of
      pseudomyxoma peritonei with synchronous pleural extension.
AB  - Extra-abdominal spread of pseudomyxoma peritonei (PMP) is a rare event, but
      extension of the tumor beyond the abdomen into the pleural cavity has been
      reported. We report a case with synchronous pleural manifestation of PMP
      confirmed during abdominal cytoreductive surgery that was managed by simultaneous
      bicavitary hyperthermic chemoperfusion. To the best of our knowledge, this is the
      first report of bicavitary hyperthermic chemoperfusion for PMP. During the
      abdominal cytoreductive surgery in a patient with known history of PMP, extensive
      disease under the right hemidiaphragm was noted, requiring partial diaphragmatic
      resection. Once the pleural space was entered, separate mucinous deposits on the
      pleural surface of the diaphragm and lung surface were observed. The involved
      portion of the right hemidiaphragm and lung were resected. The diaphragmatic
      defect was left open during the hyperthermic chemoperfusion to treat both the
      pleural and peritoneal surfaces. The patient's postoperative course was
      uneventful. Simultaneous bicavitary hyperthermic chemoperfusion is a potential
      therapeutic option for patients with pleural extension identified during
      cytoreductive surgery.

PMID- 19841368
TI  - Image of the month. Small-bowel metastasis from infiltrating lobular breast
      cancer.

PMID- 19841369
TI  - Image of the month. Incarcerated paracecal hernia.

PMID- 19841370
TI  - Feasibility of colonic and gastric standard laparoscopic procedures with a single
      skin incision approach.

PMID- 19841371
TI  - Fluorescent indocyanine green for imaging of bile ducts during laparoscopic
      cholecystectomy.

PMID- 19841372
TI  - No anastomotic leaks after colorectal surgery in rural community hospitals.

PMID- 19841373
TI  - Hospital costs of conventional and stapled 1-day hemorrhoidectomy.

PMID- 19841374
TI  - Patient safety in laparoscopic cholecystectomy.

PMID- 19841375
TI  - Pearls & Oy-sters: the orbital bruit: a poor man's angiogram.

PMID- 19841376
TI  - Teaching NeuroImages: reversible ectropion in myasthenia gravis.

PMID- 19841378
TI  - Novel susceptibility locus at chromosome 6q16.3-22.31 in a family with GEFS+.
AB  - BACKGROUND: Genetic epilepsy with febrile seizures plus (GEFS+) is a familial
      epilepsy syndrome with extremely variable expressivity. Mutations in 5 genes that
      raise susceptibility to GEFS+ have been discovered, but they account for only a
      small proportion of families. METHODS: We identified a 4-generation family
      containing 15 affected individuals with a range of phenotypes in the GEFS+
      spectrum, including febrile seizures, febrile seizures plus, epilepsy, and severe
      epilepsy with developmental delay. We performed a genome-wide linkage analysis
      using microsatellite markers and then saturated the potential linkage region
      identified by this screen with more markers. We evaluated the evidence for
      linkage using both model-based and model-free (posterior probability of linkage
      [PPL]) analyses. We sequenced 16 candidate genes and screened for copy number
      abnormalities in the minimal genetic region. RESULTS: All 15 affected subjects
      and 1 obligate carrier shared a haplotype of markers at chromosome 6q16.3-22.31,
      an 18.1-megabase region flanked by markers D6S962 and D6S287. The maximum
      multipoint lod score in this region was 4.68. PPL analysis indicated an 89%
      probability of linkage. Sequencing of 16 candidate genes did not reveal a
      causative mutation. No deletions or duplications were identified. CONCLUSIONS: We
      report a novel susceptibility locus for genetic epilepsy with febrile seizures
      plus at 6q16.3-22.31, in which there are no known genes associated with ion
      channels or neurotransmitter receptors. The identification of the responsible
      gene in this region is likely to lead to the discovery of novel mechanisms of
      febrile seizures and epilepsy.

PMID- 19841379
TI  - Characteristics of children enrolled in treatment trials for NF1-related
      plexiform neurofibromas.
AB  - OBJECTIVE: To describe the characteristics of children enrolled in treatment
      trials for neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN), PN
      tumor burden, PN-related complications, and treatment outcomes and to highlight
      the differences between characteristics of children with NF1 vs children with
      cancers entered on early phase drug trials. METHODS: Pre-enrollment
      characteristics and complications of PN were retrospectively analyzed in a cohort
      of 59 children with NF1-related PN treated on 1 of 7 clinical trials at the NIH
      between 1996 and 2007. Outcome was analyzed in a subset of 19 patients enrolled
      in phase I trials. Comparisons to children with cancer were made from a similar
      analysis performed recently. RESULTS: The median age at enrollment was 8 years.
      The median PN volume was 555 mL. Most patients had no prior chemotherapy or
      radiation, but nearly half had previous surgery for PN. PN-associated
      complications and NF1 manifestations were common, including pain (53%), other
      tumors (18%), and hypertension (8%). Investigational drug therapy was well
      tolerated. A median of 10 treatment cycles was administered. Patients with NF1
      related PN were younger, had better performance score, had less prior therapy,
      and remained on study longer than cancer patients. CONCLUSIONS: Children with NF1
      related plexiform neurofibroma (PN) enrolled in clinical trials had large tumors
      with substantial morbidity. Clinical trials in these children provide information
      about drug tolerance, cumulative toxicity, and pharmacokinetics in a younger
      population than early phase pediatric cancer trials. This report may aid in the
      evaluation of the applicability of traditional pediatric cancer trial designs and
      endpoints for NF1-related PN.

PMID- 19841380
TI  - Family history of melanoma and Parkinson disease risk.
AB  - BACKGROUND: Co-occurrence of Parkinson disease (PD) and melanoma has been
      reported in numerous studies. If this was due to common genetic mechanisms, a
      positive family history of melanoma would be associated with an excessive PD
      risk, independent of environmental risk factors for PD. METHODS: We prospectively
      examined associations between a family history of melanoma and PD among 157,036
      men and women free of PD at baseline (1990 for men and 1982 for women) who
      participated in 2 ongoing US cohorts: the Health Professional Follow-up Study and
      the Nurses' Health Study. Information on family history of melanoma in parents or
      siblings was assessed via questionnaire. Relative risks and 95% confidence
      intervals were estimated using Cox proportional hazards models and pooled using a
      fixed-effects model. RESULTS: During 14-20 years follow-up, we identified 616
      incident PD cases. A family history of melanoma in a first-degree relative was
      associated with a higher risk of PD (multivariate relative risk = 1.85; 95%
      confidence interval: 1.2, 2.8; p = 0.004), after adjusting for smoking,
      ethnicity, caffeine intake, and other covariates. In contrast, we did not observe
      significant associations between a family history of colorectal, lung, prostate,
      or breast cancer and PD risk. Interactions between melanoma family history and
      age, smoking, or caffeine intake were not significant and subgroup analyses
      according to these factors generated similar results. CONCLUSIONS: Our findings
      support the notion that melanoma and Parkinson disease (PD) share common genetic
      components. The genetic determinants of melanoma could therefore be explored as
      susceptibility candidate genes for PD.

PMID- 19841381
TI  - Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and
      bisexual men.
AB  - BACKGROUND: The purpose of this study was to evaluate the relationship between
      cognitive performance, risk factors for cardiovascular and cerebrovascular
      disease (CVD), and HIV infection in the era of highly active antiretroviral
      therapy. METHODS: We evaluated the cognitive functions of men enrolled in the
      cardiovascular disease substudy of the Multicenter AIDS Cohort Study who were
      aged > or =40 years, with no self-reported history of heart disease or
      cerebrovascular disease. Results from comprehensive neuropsychological
      evaluations were used to construct composite scores of psychomotor speed and
      memory performance. Subclinical CVD was assessed by measuring coronary artery
      calcium and carotid artery intima-media thickness (IMT), as well as laboratory
      measures, including total cholesterol, fasting glucose, glycosylated hemoglobin,
      glomerular filtration rate (estimated), and standardized blood pressure and heart
      rate measures. RESULTS: After accounting for education, depression, and race,
      carotid IMT and glomerular filtration rate were significantly associated with
      psychomotor speed, whereas IMT was associated with memory test performance. HIV
      serostatus was not significantly associated with poorer cognitive test
      performance. However, among the HIV-infected individuals, the presence of
      detectable HIV RNA in plasma was linked to lower memory performance. CONCLUSIONS:
      These findings suggest that HIV infection may not be the most important predictor
      of cognitive performance among older gay and bisexual men in the post-highly
      active antiretroviral therapy era, at least among those with access to medical
      care and to appropriate medications. Medical factors associated with normal aging
      are significantly associated with performance on neuropsychological tests, and
      good clinical management of these factors both in HIV-infected individuals and
      those at risk for infection may have beneficial effects in the short term and
      could reduce the risk of subsequent cognitive decline.

PMID- 19841382
TI  - High-sensitivity C-reactive protein predicts mortality but not stroke: the
      Northern Manhattan Study.
AB  - OBJECTIVE: To determine whether high-sensitivity C-reactive protein (hsCRP) and
      serum amyloid A (SAA) predict stroke, vascular events, and mortality in a
      prospective cohort study. BACKGROUND: Markers of inflammation have been
      associated with risk of myocardial infarction (MI). Their association with stroke
      is controversial. METHODS: The Northern Manhattan Study includes a stroke-free
      community-based cohort study in participants aged > or =40 years (median follow
      up 7.9 years). hsCRP and SAA were measured using nephelometry. Cox proportional
      hazards models were used to calculate hazard ratios (HR) and 95% confidence
      intervals (CI) for the association of markers with risk of ischemic stroke and
      other outcomes after adjusting for demographics and risk factors. RESULTS: hsCRP
      measurements were available in 2,240 participants (mean age 68.9 +/- 10.1 years;
      64.2% women; 18.8% white, 23.5% black, and 55.1% Hispanic). The median hsCRP was
      2.5 mg/L. Compared with those with hsCRP <1 mg/L, those with hsCRP >3 mg/L were
      at increased risk of ischemic stroke in a model adjusted for demographics (HR =
      1.60, 95% CI 1.06-2.41), but the effect was attenuated after adjusting for other
      risk factors (adjusted HR = 1.20, 95% CI 0.78-1.86). hsCRP >3 mg/L was associated
      with risk of MI (adjusted HR = 1.70, 95% CI 1.04-2.77) and death (adjusted HR =
      1.55, 95% CI 1.23-1.96). SAA was not associated with stroke risk. CONCLUSION: In
      this multiethnic cohort, high-sensitivity C-reactive protein (hsCRP) was not
      associated with ischemic stroke, but was modestly associated with myocardial
      infarction and mortality. The value of hsCRP and serum amyloid A may depend on
      population characteristics such as age and other risk factors.

PMID- 19841383
TI  - Cerebral infarction in POEMS syndrome: incidence, risk factors, and imaging
      characteristics.
AB  - OBJECTIVES: To determine the risk factors and incidence of cerebral infarction
      associated with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy, and skin changes) syndrome. METHODS: The Mayo Clinic dysproteinemia
      database was queried to identify patients with coded diagnosis of POEMS syndrome.
      Patients with cerebral infarction, occurring after the onset of POEMS-related
      symptoms, were selected. A retrospective observational study design was used to
      evaluate potential predictors of stroke in patients with POEMS syndrome. RESULTS:
      A total of 9 patients (10%; 95% confidence interval 5.4-17.9) with cerebral
      infarction were identified (2 women, 22%). Traditional stroke risk factors were
      not significantly different between the stroke and nonstroke subgroups, but
      hematologic abnormalities such as elevated platelet count and bone marrow
      plasmacytosis differed between the 2 groups. Cerebral infarction occurrence after
      successful treatment of the underlying condition was not observed. CT and MRI
      data demonstrated a wide spectrum of infarct topography in these patients. Common
      stroke etiologies comprised suspected vascular structural abnormalities leading
      to vessel dissection and stenosis, in addition to embolism from a proximal
      source. CONCLUSIONS: The 5-year risk of cerebral infarction in patients with
      POEMS syndrome is 13.4%. Evidence of plasma cell proliferation within the bone
      marrow and elevated serum platelet count led to increased risk of cerebral
      infarction in this population. We conclude that known modifiable stroke risk
      factors should be aggressively managed. Treatment of thrombocytosis should be
      considered in patients without a contraindication. Treatment of the syndrome may
      be the best approach to decreasing risk of cerebral infarction in these patients.

PMID- 19841384
TI  - Sleep-related breathing and sleep-wake disturbances in ischemic stroke.
AB  - BACKGROUND: Sleep-related breathing disturbances (SDB) and sleep-wake
      disturbances (SWD) are often neglected in stroke patients. Recent studies suggest
      that they are frequent and have an impact on stroke outcome. METHODS: We review
      current knowledge about frequency, clinical presentation, and consequences of
      poststroke SDB and SWD, and discuss treatment options. RESULTS: SDB, presenting
      with obstructive, central, or mixed apneas, is present in 50%-70% of stroke
      patients. We recommend screening for SDB in all stroke patients by respirography.
      Continuous positive airway pressure (CPAP) is the treatment of choice for
      obstructive SDB, which reverses the vascular risk of the patients. In the absence
      of controlled trials, CPAP treatment should be reserved for patients with severe
      obstructive SDB, daytime symptoms (e.g., sleepiness), or high cardiovascular risk
      profile. Oxygen and adaptive servoventilation may be used for central SDB. SWD
      including insomnia, disturbances of wakefulness (hypersomnia, excessive daytime
      sleepiness, fatigue), sleep-related movement disorders (restless legs syndrome,
      periodic limb movements during sleep), and parasomnias (REM sleep behavior
      disorder) are found in 10%-50% of patients. SWD are associated with cognitive
      disturbances and may compromise neurologic recovery. Hypnotics and sedative
      antidepressants may aggravate SDB and neurologic recovery and should be used with
      caution. For disturbances of wakefulness, dopaminergic drugs, modafinil, or
      activating antidepressants may be considered. Poststroke sleep-related movement
      disorders can be treated with dopaminergic drugs; REM sleep behavior disorder
      with clonazepam. CONCLUSIONS: Sleep-related breathing disturbances and sleep-wake
      disturbances are frequent conditions that affect stroke outcome. In view of
      existing treatment options, these conditions deserve the neurologist's awareness.

PMID- 19841385
TI  - Astrocyte-neuron interactions: implications for epilepsy.

PMID- 19841386
TI  - Abraham Lincoln did not have type 5 spinocerebellar ataxia.
AB  - An autosomal dominant genetic disorder, type 5 spinocerebellar ataxia (SCA5),
      occurs in multiple descendants of one paternal uncle and one paternal aunt of
      President Abraham Lincoln. It has been suggested that Lincoln himself had the
      disease and that his DNA should be tested for an SCA5-conferring gene. Herein, I
      review the pertinent phenotypes of Lincoln, his father, and his paternal
      grandmother, and conclude that 1) Lincoln's father did not have SCA5, and,
      therefore, that Lincoln was not at special risk of the disease; 2) Lincoln had
      neither subclinical nor visible manifestations of SCA5; 3) little evidence
      suggests SCA5 is a "Lincolnian" disorder; and 4) without additional evidence,
      Lincoln's DNA should not be tested for SCA5.

PMID- 19841387
TI  - Normalization of hypocretin-1 in narcolepsy after intravenous immunoglobulin
      treatment.

PMID- 19841388
TI  - Varicella zoster virus-associated polyradiculoneuritis.

PMID- 19841389
TI  - Re: Practice parameters and technology assessments: what they are, what they are
      not, and why you should care.

PMID- 19841390
TI  - Lost in a jungle of evidence: we need a compass. Practice parameters and
      technology assessments: what they are, what they are not, and why you should
      care.

PMID- 19841391
TI  - Lost in a jungle of evidence: we need a compass.

PMID- 19841394
TI  - Fractional photothermolysis: a new therapeutic modality for xanthelasma.

PMID- 19841395
TI  - Large sample of nephrogenic systemic fibrosis cases from a single institution.
AB  - OBJECTIVES: To estimate and stratify the risk of development of nephrogenic
      systemic fibrosis (NSF) in well-defined at-risk subpopulations from a large
      single institution, and to perform a single-institution case series study of
      patients with biopsy-proven NSF. DESIGN: Retrospective cohort of patients exposed
      to gadolinium-based contrast agents (GBCAs) at a single institution during an 8
      year period (January 1, 1999, to December 31, 2006), and a case series study of
      patients with biopsy-proven NSF. SETTING: A primary, secondary, and tertiary
      health care center that treated more than 2.2 million outpatients and had 135 000
      hospital admissions in 2007. Patients A total of 94 917 patients exposed to
      GBCAs; patients at risk for NSF (3779 patients on hemodialysis, 1694 patients
      with renal transplants, and 717 patients with liver transplants, a well-defined
      subgroup that includes patients at risk for reduced renal function); and 61
      patients with a clinical diagnosis of NSF. MAIN OUTCOME MEASURE: Risk estimate
      for NSF. RESULTS: The risk of development of NSF is 1.0% for patients who undergo
      hemodialysis (8 of 827), 0.8% for patients with renal transplantation (4 of 527),
      and 0% for patients with liver transplantation at our institution (0 of 327).
      CONCLUSIONS: Despite the limitations, this study, which reviewed a large number
      of patients who underwent intravascular GBCA injections, demonstrates a 77-fold
      higher risk of NSF among patients who undergo hemodialysis and a 69-fold higher
      risk in patients with renal transplantation. This increased risk is thought to be
      associated with poor clearance of most GBCAs.

PMID- 19841396
TI  - Highly sensitive multivariable assay detection of melanocytic differentiation
      antigens and angiogenesis biomarkers in sentinel lymph nodes with melanoma
      micrometastases.
AB  - OBJECTIVES: To evaluate the prognostic value of melanocytic differentiation
      antigens and angiogenesis biomarkers in sentinel lymph nodes (SLNs) with melanoma
      micrometastases. DESIGN: Prognostic study of an inception cohort. SETTING:
      Academic research. Patients Between July 1, 1999, and July 31, 2002, all patients
      who had primary cutaneous or mucosal melanomas that have a Breslow depth of 1.5
      mm or greater, ulceration, or Clark level IV or V, or had SLN biopsies. MAIN
      OUTCOME MEASURES: By the use of quantitative reverse transcription-polymerase
      chain reaction, the expression of the following was analyzed in SLNs: 2
      melanocytic differentiation antigens (tyrosinase [P17646] and melanoma antigen
      recognized by T cells [MART-1; Q16655]) and genes involved in angiogenesis (VEGF
      [NM_001025366] and VEGFR2 [AF035121]), lymphangiogenesis (VEGFC [NM_005429],
      VEGFR3 [X68203], LYVE1 [NM_016164], and PROX1 [002763]), and invasion (uPA
      [NM_002658], PAI1 [NM_00602], and EMMPRIN [L10240]). Outcome measures were the
      association of these melanocytic differentiation antigens and angiogenesis
      biomarkers with clinicopathologic characteristics of patients, and an evaluation
      of the prognostic value for relapse-free survival and overall survival. RESULTS:
      Ninety-one patients were included, with a median follow-up period of 41 months.
      Micrometastases were present in 15% (14 of 91) of patients. Tyrosinase (P <
      .001), MART-1 (P < .001), vascular endothelial growth factor 121 (VEGF(121)) (P =
      .007), and PAI1 (P = .02) expression was significantly associated with
      micrometastasis. In univariate analysis, histologic findings and tyrosinase and
      MART-1 expression were significantly associated with relapse-free survival.
      Tyrosinase and MART-1 expression was associated with overall survival. A multiple
      Cox proportional hazards regression model identified negative histologic findings
      and tyrosinase expression that exceeded 27 copies/copy of TATA box-binding
      protein (third quartile) as significantly associated with an increased risk of
      relapse or death. CONCLUSIONS: Quantitative assessment of melanocytic
      differentiation antigens in SLNs, which has prognostic value, is more specific
      than qualitative assessment. Prognosis may be more effectively predicted by the
      combination of quantitative assessment of melanocytic differentiation antigens in
      SLNs with histologic assessment. A significant association was found between the
      presence of micrometastases and the expression of angiogenesis biomarkers.

PMID- 19841398
TI  - Molecular analysis of aggressive microdermabrasion in photoaged skin.
AB  - OBJECTIVE: To investigate dermal remodeling effects of crystal-free
      microdermabrasion on photodamaged skin. DESIGN: Biochemical analyses of human
      skin biopsy specimens following microdermabrasion treatment in vivo. SETTING:
      Academic referral center. PARTICIPANTS: Volunteer sample of 40 adults, aged 50 to
      83 years, with clinically photodamaged forearms. Intervention Focal
      microdermabrasion treatment with diamond-studded handpieces of varying
      abrasiveness on photodamaged forearms and serial biopsies at baseline and various
      times after treatment. MAIN OUTCOME MEASURES: Quantitative polymerase chain
      reaction, immunohistochemistry, and enzyme-linked immunosorbent assay were used
      to quantify changes in inflammatory, proliferative, and remodeling effectors of
      normal wound healing. Type I and type III procollagen served as the main outcome
      marker of dermal remodeling. RESULTS: Coarse-grit microdermabrasion induces a
      wound healing response characterized by rapid increase in induction of
      cytokeratin 16 and activation of the AP-1 transcription factor in the epidermis.
      Early inflammation was demonstrated by induction of inflammatory cytokines,
      antimicrobial peptides, and neutrophil infiltration in the dermis. AP-1
      activation was followed by matrix metalloproteinase-mediated degradation of
      extracellular matrix. Consistent with this wound-healing response, we observed
      significant remodeling of the dermal component of the skin, highlighted by
      induction of type I and type III procollagen and by induction of collagen
      production enhancers heat shock protein 47 and prolyl 4-hydroxylase. Dermal
      remodeling was not achieved when microdermabrasion was performed using a medium
      grit handpiece. CONCLUSIONS: Microdermabrasion using a coarse diamond-studded
      handpiece induces a dermal remodeling cascade similar to that seen in incisional
      wound healing. Optimization of these molecular effects is likely the result of
      more aggressive treatment with a more abrasive handpiece.

PMID- 19841399
TI  - Practical guidelines for evaluation of loose anagen hair syndrome.
AB  - OBJECTIVES: To better categorize the epidemiologic profile, clinical features,
      and disease associations of loose anagen hair syndrome (LAHS) compared with other
      forms of childhood alopecia. DESIGN: Retrospective survey. SETTING: Academic
      pediatric dermatology practice. Patients Three hundred seventy-four patients with
      alopecia referred from July 1, 1997, to June 31, 2007. MAIN OUTCOME MEASURES:
      Epidemiologic data for all forms of alopecia were ascertained, such as sex, age
      at onset, age at the time of evaluation, and clinical diagnosis. Patients with
      LAHS were further studied by the recording of family history, disease
      associations, hair-pull test or biopsy results, hair color, laboratory test
      result abnormalities, initial treatment, and involvement of eyelashes, eyebrows,
      and nails. RESULTS: Approximately 10% of all children with alopecia had LAHS. The
      mean age (95% confidence interval) at onset differed between patients with LAHS
      (2.8 [1.2-4.3] years) vs patients without LAHS (7.1 [6.6-7.7] years) (P < .001),
      with 3 years being the most common age at onset for patients with LAHS. All but 1
      of 37 patients with LAHS were female. The most common symptom reported was thin,
      sparse hair. Family histories were significant for LAHS (n = 1) and for alopecia
      areata (n = 3). In 32 of 33 patients, trichograms showed typical loose anagen
      hairs. Two children had underlying genetic syndromes. No associated laboratory
      test result abnormalities were noted among patients who underwent testing.
      CONCLUSIONS: Loose anagen hair syndrome is a common nonscarring alopecia in young
      girls with a history of sparse or fine hair. Before ordering extensive blood
      testing in young girls with diffusely thin hair, it is important to perform a
      hair-pull test, as a trichogram can be instrumental in the confirmation of a
      diagnosis of LAHS.

PMID- 19841400
TI  - Rates of skin cancer screening and prevention counseling by US medical residents.
AB  - OBJECTIVE: To determine factors related to residents' self-reported skill level
      for the skin cancer examination (SCE). DESIGN: Survey of residents in November
      2003. SETTING: Four US residency programs. PARTICIPANTS: Medical residents in
      family medicine, pediatrics, obstetrics and gynecology, and internal medicine and
      specialists. MAIN OUTCOME MEASURE: Proportion of residents reporting their
      current skill level for the performance of the SCE. RESULTS: Of 454 surveys
      distributed, 342 residents completed the survey (75.3% response rate). Clinical
      training for the SCE during residency was infrequent. During residency, 75.8%
      were never trained in the SCE, 55.3% never observed an SCE, and 57.4% never
      practiced the examination. Only 15.9% of residents reported being skilled in the
      SCE. However, the conduct of 4 SCEs (or slightly more than 1 per each year of
      residency) was associated with manifold increases in self-reported skill levels.
      CONCLUSIONS: Information now collected from 7 medical schools and 4 residency
      programs underscores the need for more supervised opportunities to enable
      physicians in training to perform an SCE during routine patient examinations.

PMID- 19841401
TI  - Reflectance confocal microscopy and features of melanocytic lesions: an internet
      based study of the reproducibility of terminology.
AB  - OBJECTIVE: To test the interobserver and intraobserver reproducibility of the
      standard terminology for description and diagnosis of melanocytic lesions in in
      vivo confocal microscopy. DESIGN: A dedicated Web platform was developed to train
      the participants and to allow independent distant evaluations of confocal images
      via the Internet. SETTING: Department of Dermatology, University of Modena and
      Reggio Emilia, Modena, Italy. PARTICIPANTS: The study population was composed of
      15 melanomas, 30 nevi, and 5 Spitz/Reed nevi. Six expert centers were invited to
      participate at the study. Intervention Evaluation of 36 features in 345 confocal
      microscopic images from melanocytic lesions. MAIN OUTCOME MEASURE: Interobserved
      and intraobserved agreement, by calculating the Cohen kappa statistics measure
      for each descriptor. RESULTS: High overall levels of reproducibility were shown
      for most of the evaluated features. In both the training and test sets there was
      a parallel trend of decreasing kappa values as deeper anatomic skin levels were
      evaluated. All of the features, except 1, used for melanoma diagnosis, including
      roundish pagetoid cells, nonedged papillae, atypical cells in basal layer,
      cerebriform clusters, and nucleated cells infiltrating dermal papillae, showed
      high overall levels of reproducibility. However, less-than-ideal reproducibility
      was obtained for some descriptors, such as grainy appearance of the epidermis,
      junctional thickening, mild atypia in basal layer, plump bright cells, small
      bright cells, and reticulated fibers in the dermis. Conclusion The standard
      consensus confocal terminology useful for the evaluation of melanocytic lesions
      was reproducibly recognized by independent observers.

PMID- 19841402
TI  - Efficacy and safety of microfoam sclerotherapy in a patient with Klippel
      Trenaunay syndrome and a patent foramen ovale.
AB  - BACKGROUND: Sclerotherapy with polidocanol microfoam injection under duplex
      guidance is a new treatment for venous malformations associated with Klippel
      Trenaunay syndrome. Multidetector-row computed tomography (MDCT) venography is
      extremely helpful in the assessment of disease extension and the planning of
      therapy. Observation In this particular case, MDCT venography demonstrated the
      origin, course, and relationship to adjacent anatomical structures of aberrant
      vessels that configure the superficial venous system with an anatomically normal
      and patent deep venous system. At the end of the treatment, which consisted of 8
      sessions of microfoam sclerotherapy within 12 months, a considerable reduction in
      the number and size of the percutaneously treated aberrant veins was observed.
      The obvious clinical improvement was objectively demonstrated with MDCT
      venography, which showed clear reduction in the number and size of treated veins.
      Further clinical investigation performed because of isolated migraine episodes
      related to the sclerotherapy session revealed that the patient had a patent
      foramen ovale. A transcranial Doppler examination during the procedure showed
      middle cerebral artery bubbles, which indicated right-to-left shunt. No cerebral
      damage was observed in a subsequent diffusion-weighted magnetic resonance
      examination. CONCLUSIONS: Microfoam sclerotherapy is an effective treatment
      option in patients with Klippel-Trenaunay syndrome. MDCT venography allows
      diagnosis of the disease, planning of therapy, and assessment of response to
      treatment. Although foam-induced microembolism is a common phenomenon during
      sclerotherapy, in this report we demonstrate that polidocanol microfoam prepared
      with a low-nitrogen gas mixture is safe in a patient with a patent foramen ovale.

PMID- 19841403
TI  - Adenosquamous carcinoma of the skin: a case series.
AB  - BACKGROUND: Adenosquamous carcinoma is an uncommon cutaneous malignant neoplasm
      with mixed glandular and squamous differentiation and a propensity for aggressive
      clinical behavior. OBSERVATIONS: Of 27 patients diagnosed as having adenosquamous
      carcinoma, 19 were men and 5 were immunosuppressed. The mean age was 74 years.
      The majority of tumors were located on the face and scalp (19 of 27 [70%]) or
      upper extremity (4 of 27 [15%]). Squamous and glandular differentiation was
      characteristic. Thickness of the primary lesion ranged from 1.2 to 9.2 mm, with
      all tumors extensively invading the reticular dermis. Perineural invasion was
      seen in 4 of 27 primary cases (15%). Although 3 of 6 patients treated with Mohs
      micrographic surgery had subsequent locoregional recurrences, there was no
      evidence of distant metastasis after a mean of 2.3 years of patient follow-up.
      CONCLUSIONS: Adenosquamous carcinoma is best considered as a locally aggressive
      high-risk subtype of cutaneous squamous cell carcinoma. Tumor thickness and
      perineural invasion are high-risk histopathological attributes, and
      immunosuppression is an important clinical risk factor. Although Mohs
      micrographic surgery may be the best initial treatment, locoregional recurrence
      is common.

PMID- 19841404
TI  - Subcorneal pustular dermatosis-type IgA pemphigus with autoantibodies to
      desmocollins 1, 2, and 3.
AB  - BACKGROUND: IgA pemphigus is a rare neutrophilic acantholytic autoimmune disease
      that is characterized by IgA deposits on keratinocyte cell surfaces. Clinically
      and histologically, IgA pemphigus is divided into 2 major subtypes: subcorneal
      pustular dermatosis and intraepidermal neutrophilic IgA dermatosis. We report the
      first case of subcorneal pustular dermatosis-type IgA pemphigus that showed
      reactivity to all 3 isoforms of the desmocollin family by indirect
      immunofluorescence microscopy of COS7 cells transfected with desmocollin 1, 2, or
      3. OBSERVATIONS: We describe a 94-year-old woman with IgA pemphigus with a unique
      immunopathologic pattern. Direct immunofluorescence microscopy revealed IgA
      deposits throughout the entire epidermis, with stronger staining in the upper
      epidermis. The autoantibodies from this patient did not show IgA or IgG
      reactivity with desmogleins via immunoblotting or enzyme-linked immunosorbent
      assay. By indirect immunofluorescence by the use of COS7 cells transfected with
      desmocollin 1, 2, or 3, IgA autoantibodies in a serum sample from our patient
      clearly reacted with all of them. CONCLUSIONS: The pathophysiology and
      autoantigen profile of bullous autoimmune diseases, especially pemphigus and its
      subforms, are more complex than previously believed. Because pemphigus seems to
      be a heterogeneous disorder, further studies are needed to evaluate the
      complexity of the disease.

PMID- 19841406
TI  - UV-A1 therapy for nephrogenic systemic fibrosis.
AB  - BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a rare sclerosing skin
      condition associated with end-stage renal disease and gadolinium exposure.
      Therapy for NSF is challenging, with few options other than preventing exposure
      to gadolinium and improving renal function through transplant. However, in some
      cases neither of these options is tenable. We report the successful use of UV-A1
      phototherapy in 4 patients with NSF. OBSERVATIONS: Four patients with NSF were
      treated with UV-A1 phototherapy at a tertiary medical center from 2005 through
      2007. To our knowledge, it is unique to this series that all patients were
      receiving hemodialysis before, during, and after therapy with UV-A1. All
      experienced improvement in the degree of induration, and 2 experienced
      improvement in mobility of the hands and legs. Total treatments ranged from 22
      treatments (with a cumulative dose of 1855 J/cm(2)) to 50 treatments (total UV-A1
      exposure, 3850 J/cm(2)). No adverse events were observed. CONCLUSIONS: Although
      no patient had complete resolution of indurated plaques, the improvement was
      substantial. For 2 patients, it resulted in a resumption of hand and leg
      mobility. As a result, UV-A1 therapy may represent a treatment for NSF when
      kidney transplantation is not an option or is delayed. Limitations of this study
      include the lack of a controlled trial, lack of quantification of gadolinium
      levels within tissue, and the lack of a defined grading scale for NSF severity.

PMID- 19841405
TI  - Detection of clonal T cells in the circulation of patients with nephrogenic
      systemic fibrosis.
AB  - BACKGROUND: Nephrogenic systemic fibrosis is a sclerodermalike disease in
      patients with acute or chronic renal insuffiency related to administration of
      gadolinium-containing contrast agents. Previous studies have demonstrated clonal
      T-cell populations in the blood of patients with systemic sclerosis, suggesting
      that these cells may be involved in the pathogenesis of the disease. Facing the
      clinical similarities of both diseases, we hypothesized that clonal expansion of
      T cells could be present in nephrogenic systemic fibrosis as well. OBSERVATIONS:
      Findings from polymerase chain reaction and high-resolution capillary
      electrophoresis for T-cell receptor gamma gene rearrangement analysis showed that
      all 6 prospectively evaluated patients (100%) with nephrogenic systemic fibrosis
      had detectable clonal T cells in their peripheral blood. In contrast, only 4 of
      the 15 control patients (27%) with chronic renal failure and none of the 12
      healthy individuals analyzed in this study had evidence for T-cell clonality
      using the same type of examination. Clonal T-cell-positive patients with systemic
      sclerosis have previously been reported to better respond to extracorporeal
      photopheresis. However, this was not the case in 2 of our patients with
      nephrogenic systemic fibrosis. Conclusion As in systemic sclerosis, clonally
      expanded T-cell populations could play a critical role in the pathogenesis of
      nephrogenic systemic fibrosis, probably as an in vivo-activated inflammatory
      response to gadolinium exposure.

PMID- 19841407
TI  - A glimpse of future management of melanoma.

PMID- 19841408
TI  - Estimates of risk, empirical treatment observations, and unexpected laboratory
      findings reveal the complexity of nephrogenic systemic fibrosis.

PMID- 19841409
TI  - Slowly enlarging nodule on a finger.

PMID- 19841410
TI  - Multiple blue macules and papules on the scalp.

PMID- 19841411
TI  - Asymptomatic red plaque on the leg of a 7-year-old girl.

PMID- 19841412
TI  - Orange-yellow diffuse cutaneous eruption in an 82-year-old woman.

PMID- 19841414
TI  - Physician workforce for acne care in the United States, 2003 through 2005.

PMID- 19841413
TI  - Defining wound microbial flora: molecular microbiology opening new horizons.

PMID- 19841415
TI  - Squamous cell carcinoma in solid organ transplant recipients: influences on
      perception of risk and optimal time to provide education.

PMID- 19841416
TI  - Large amelanotic melanoma and vitiligo.

PMID- 19841417
TI  - A new dermoscopic finding in healthy children: dirt!

PMID- 19841418
TI  - Axillary web syndrome or cording, a variant of mondor disease, following axillary
      surgery.

PMID- 19841419
TI  - Classic Kaposi sarcoma treated with intralesional 5-aminolevulinic acid injection
      photodynamic therapy.

PMID- 19841420
TI  - Acute edema/cutaneous distention syndrome associated with refeeding in a patient
      with anorexia nervosa.

PMID- 19841421
TI  - Dermoscopic features of Birt-Hogg-Dube syndrome.

PMID- 19841422
TI  - Child neurologists should be interested in brain tumors!

PMID- 19841423
TI  - Introduction to a special issue on pediatric neuro-oncology.

PMID- 19841424
TI  - Neuroimaging of pediatric brain tumors: from basic to advanced magnetic resonance
      imaging (MRI).
AB  - In this review, the basic magnetic resonance concepts used in the imaging
      approach of a pediatric brain tumor are described with respect to different
      factors including understanding the significance of the patient's age. Also
      discussed are other factors directly related to the magnetic resonance scan
      itself including evaluating the location of the tumor, determining if the lesion
      is extra-axial or intra-axial, and evaluating the contrast characteristics of the
      lesion. Of note, there are key imaging features of pediatric brain tumors, which
      can give information about the cellularity of the lesion, which can then be
      confirmed with advanced magnetic resonance imaging (MRI) techniques. The second
      part of this review will provide an overview of the major advanced MRI techniques
      used in pediatric imaging, particularly, magnetic resonance diffusion, magnetic
      resonance spectroscopy, and magnetic resonance perfusion. The last part of the
      review will provide more specific information about the use of advanced magnetic
      resonance techniques in the evaluation of pediatric brain tumors.

PMID- 19841425
TI  - The evolving role of surgery in the management of pediatric brain tumors.
AB  - Surgery is an integral component and typically the first line of therapy for
      children with central nervous system tumors. The outcome with regard to surgical
      morbidity and disease control can be greatly influenced by the initial care that
      these children receive. Conventional aims of neurosurgery including tumor
      removal, management of hydrocephalus, and diagnostic sampling have been radically
      modified with innovative technologies such as navigational guidance, functional
      mapping, endoscopic surgery, second-look surgery, and physiologic imaging. The
      overall role of the pediatric neurosurgeon in caring for children with nervous
      system tumors is also expanding to include unconventional responsibilities
      including disease staging, tissue procurement, and drug delivery. It is thus
      anticipated that the pediatric neurosurgeon will be increasingly relied upon for
      oncologic therapeutic strategies and should thus remain abreast of forthcoming
      information and technologies.

PMID- 19841426
TI  - Histology and molecular pathology of pediatric brain tumors.
AB  - In recent years, brain tumors have become the single most frequent cause of
      cancer-related mortality in children, although their frequency is approximately
      50% less than leukemia. According to the classification of the World Health
      Organization, histopathological diagnosis is of paramount importance for
      clinicians to choose the most appropriate treatment option and tailor treatment
      intensity to disease risk. However, histopathological assessment is often
      difficult, and adding molecular information to classic neuropathological analyses
      may help ensure diagnostic accuracy, improve risk stratification of patients
      within a given tumor entity, and help in identifying novel therapeutic targets
      for an individualized treatment approach. Therefore, this review focuses both on
      established histopathology as well as on molecular features in the most important
      brain tumors in children.

PMID- 19841427
TI  - Radiation therapy for pediatric central nervous system tumors.
AB  - Radiation therapy is an important component of treatment of many pediatric
      central nervous system tumors. The radiation treatment target is determined by
      tumor histology, extent of disease, anticipated pattern of spread, and expected
      pattern of failure. Children cured of their tumors live to experience the long
      term sequelae of radiation treatment, including developmental, neurocognitive,
      neuroendocrine, and hearing late effects. The development of more conformal
      radiation techniques has decreased inadvertent radiation dose to normal tissues
      and should decrease long-term treatment sequelae that are the result of normal
      tissue radiation. Intensity-modulated radiation therapy improves treatment
      conformity and decreases high dose to nearby normal tissues; however, it delivers
      a larger volume of low- and intermediate-dose radiation. Proton radiation
      eliminates exit dose to normal tissues, thereby eliminating approximately 50% of
      unnecessary radiation to normal tissues. The long-term clinical benefits of
      proton radiation in the pediatric population are just beginning to be reported in
      the literature.

PMID- 19841429
TI  - Medulloblastoma.
AB  - Medulloblastoma is the most common malignant brain tumor in children. Patients
      with medulloblastoma are stratified into ''standard'' and ''high'' risk
      categories based on age at diagnosis, degree of surgical resection, and disease
      spread. In children older than 3 years of age, the long-term survival can be
      achieved in approximately 85% of standard risk patients and 70% of high risk
      patients with a combination of chemotherapy and irradiation. Younger children,
      particularly infants, are at a significantly higher risk of side-effects of
      treatment. Despite tremendous progress in the field of molecular biology of
      medulloblastoma, much remains to be achieved in understanding the pathogenesis,
      critical pathways responsible for medulloblastoma, and molecular risk
      stratification, and in devising treatment strategies with even better survival
      and less long-term sequelae.

PMID- 19841430
TI  - Ependymoma: an update.
AB  - The authors provide an update on most issues related to biology, diagnosis, and
      treatment of children with ependymoma based on a literature review. Ependymoma is
      the third most common brain tumor in children and overall survival ranges from
      24% to 75% at 5 years. The extent of surgical resection remains the principal
      risk factor that clearly influences outcome. The influence of age, location,
      grade, or stage has proved to be more controversial. Current standard therapy
      includes surgical resection and radiotherapy. Chemotherapy has a role in infants
      to avoid/delay radiotherapy and can be helpful to improve resectability. About
      half of patients will experience relapse, and outcome is dismal. New radiation
      modalities, reirradiation, chemotherapy, or targeted agents have been tested with
      promising results. Results of multi-institutional clinical trials are awaited to
      determine the best first-line treatment, while results of early phase I/ II
      trials will explore directed therapies based on new biologic factors.

PMID- 19841428
TI  - Pediatric low-grade gliomas.
AB  - Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different
      histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by
      supratentorial diffuse fibrillary astrocytomas. Recent research has implicated
      activation of the RAS/RAF/MEK pathway in tumorigenesis of these tumors. Surgery
      is the mainstay of therapy. Overall survival rates for patients whose tumors are
      completely resected are 90% or greater, 10 years from diagnosis. Conversely, most
      optic pathway/hypothalamic, deep midline, and brain stem gliomas have minimal
      potential for resection; these tumors can be difficult to treat and deserve
      special attention. Combination chemotherapy is currently recommended as front
      line adjuvant treatment for progressive or recurrent tumors. Second-line
      radiotherapy can also improve overall survival but is associated with more
      frequent and significant neurocognitive, endocrine, and other long-term
      toxicities.

PMID- 19841431
TI  - Central nervous system germ cell tumors: classification, clinical features, and
      treatment with a historical overview.
AB  - Central nervous system germ cell tumors are neoplasms that affect children and
      young adults. They are subclassified into germinoma and nongerminomatous germ
      cell tumors. The latter include teratoma (mature teratoma, immature teratoma,
      teratoma with malignant transformation), choriocarcinoma, embryonal carcinoma,
      yolk sac tumors, and mixtures of these entities. Germinoma with
      syncytiotrophoblastic giant cells is a variant of germinoma. Germinomas respond
      well to radiation therapy, but late sequelae due to irradiation have been
      reported. The results of radiation treatment alone for nongerminomatous germ cell
      tumor are not satisfactory. Combination radiochemotherapy has been applied, and
      this yields a good outcome with less toxicity for germinomas and better survival
      of nongerminomatous germ cell tumors. This article also discusses other issues,
      including the controversy regarding spinal irradiation and the treatment of
      recurrent disease.

PMID- 19841433
TI  - Late effects of therapy for pediatric brain tumor survivors.
AB  - Approximately 2 of every 3 of all pediatric patients with brain tumors will be
      long-term survivors. However, there is a steep cost for pediatric brain tumor
      survivors, and the group as a whole faces significantly more late effects than
      many other survivors of pediatric cancers. Most of these effects can be
      attributed to direct neurologic damage to the developing brain caused by the
      tumor and its removal, the long-term toxicity of chemotherapy, or the effects of
      irradiation on the central nervous system. The late effects experienced by
      childhood brain tumor survivors involve multiple domains. This article will
      review the significant late effects that occur within the medical,
      neurocognitive, psychosocial, and economic domains of the survivorship
      experience. We conclude by discussing how the late effects in different domains
      often coexist and can create a complex set of obstacles that pose significant
      challenges for a survivor of a pediatric brain tumor on a daily basis.

PMID- 19841432
TI  - Neurologic sequelae of brain tumors in children.
AB  - Neurologic signs and symptoms are often the initial presenting features of a
      primary brain tumor and may also emerge during the course of therapy or as late
      effects of the tumor and its treatment. Variables that influence the development
      of such neurologic complications include the type, size, and location of the
      tumor, the patient's age at diagnosis, and the treatment modalities used.
      Heightened surveillance and improved neuroimaging modalities have been
      instrumental in detecting and addressing such complications, which are often not
      appreciated until many years after completion of therapy. As current brain tumor
      therapies are continually refined and newer targeted therapies are developed, it
      will be important for future cooperative group studies to include systematic
      assessments to determine the incidence of neurologic complications and to provide
      a framework for the development of novel strategies for prevention and
      intervention.

PMID- 19841434
TI  - Diagnosis and treatment of childhood brain tumors: current perspectives.

PMID- 19841437
TI  - Dermatomal somatosensory evoked potentials and electrical perception thresholds
      during recovery from cervical spinal cord injury.
AB  - BACKGROUND: Dermatomal somatosensory evoked potentials (dSSEPs) not only provide
      a neurophysiological readout comparable with conventional SSEPs but also provide
      an opportunity to track changes in sensory function corresponding to individual
      dermatomes (ie, a single spinal segment) above, at, and below the level of spinal
      cord injury (SCI). OBJECTIVES: This study aimed to determine the reliability and
      responsiveness of dSSEPs and electrical perception thresholds (EPTs) to monitor
      changes in sensory function after cervical SCI. METHODS: Initial and follow-up
      dSSEPs and EPTs were recorded from cervical dermatomes (C4-C8) of patients with
      traumatic tetraplegia (C3-C8; ASIA Impairment Scale A-D) during recovery after
      SCI (n = 18). RESULTS: Follow-up examination of 74 initial dSSEPs unaffected by
      SCI (n = 18) revealed no significant change in latency (Delta = 0.0 +/- 1.4 ms; P
      = .9) or EPT sensitivity (Delta = 0.1 +/- 0.8 mA; P = .3). In 41 dSSEPs initially
      delayed after SCI (n = 14), latencies significantly decreased on follow-up
      examination (Delta = -3.1 +/- 2.9 ms; P < .01) without a corresponding increase
      in sensitivity of the EPT (Delta = 0.2 +/- 3.4 mA; P = .7). dSSEPs that were not
      measurable initially were subsequently recorded in 11 dermatomes (n = 5) on
      follow-up examination. This conversion of abolished-to-recordable dSSEPs was
      often preceded by the perception of an initial EPT and associated with a
      concomitant recovery of EPT at follow-up. CONCLUSION: SSEPs and EPT can be
      reliably recorded to monitor changes in sensory function for each individual
      spinal segment after cervical SCI. dSSEPs may be potentially useful to monitor
      the safety of a therapeutic drug or cell transplant in early-phase (I/II)
      clinical trials as well as document the potential efficacy of interventions where
      the standard neurological assessment might not detect subtle therapeutic effects.

PMID- 19841436
TI  - Vitamin E protects against oxidative damage and learning disability after mild
      traumatic brain injury in rats.
AB  - BACKGROUND: Reactive oxygen species induce neuronal damage, and their role in
      reducing synaptic plasticity and function is beginning to be understood. Vitamin
      E is a potent reactive oxygen species scavenger, which has the potential to
      reduce oxidative damage encountered after traumatic brain injury (TBI). Brain
      derived neurotrophic factor (BDNF) can facilitate synaptic function and support
      learning by modulating the CaMKII system, synapsin I, and cAMP-response element
      binding protein (CREB). The elevation of superoxide dismutase (SOD) and Sir2
      (silent information regulator 2) play an important role in resistance to
      oxidative stress. OBJECTIVE: We examined the possibility that vitamin E
      supplemented in the diet may help counteract the effects of TBI on the molecular
      substrates underlying synaptic plasticity and cognitive function in the
      hippocampus. METHODS: Rats were fed a regular diet with or without 500 IU/kg of
      vitamin E for 4 weeks (n = 6-8 per group) before a mild fluid percussion injury
      (FPI) was performed. RESULTS: FPI increased protein oxidation as evidenced by
      elevated levels of protein carbonyls and reduced levels of SOD and Sir2. In
      addition, FPI resulted in poor performance in the Morris water maze, which was
      accompanied by reduced levels of BDNF and its downstream effectors on synaptic
      plasticity, synapsin I, CREB, and CaMKII. Supplementation of vitamin E in the
      diet counteracted all the observed effects of FPI. CONCLUSIONS: These results
      suggest that vitamin E dietary supplementation can protect the brain against the
      effects of mild TBI on synaptic plasticity and cognition, using molecular systems
      associated with the maintenance of long-term plasticity, such as BDNF and Sir2.

PMID- 19841438
TI  - Summaries for patients. Effect of treatment with fluticasone with and without
      salmeterol on airway inflammation and lung function in patients with chronic
      obstructive pulmonary disease: a randomized trial.

PMID- 19841439
TI  - Summaries for patients. Cost-effectiveness of human papillomavirus vaccination
      and cervical cancer screening in women older than 30 years in the United States.

PMID- 19841440
TI  - Summaries for patients. Risk for hospitalization for infection in patients who
      have had splenectomy.

PMID- 19841441
TI  - ACP Journal Club. Stratification for exploring heterogeneity in systematic
      reviews.

PMID- 19841442
TI  - ACP Journal Club. Review: Preoperative smoking cessation interventions reduce
      postoperative complications.

PMID- 19841443
TI  - ACP Journal Club. Adding prompt revascularization to medical therapy did not
      reduce mortality or CV events in patients with type 2 diabetes and CAD.

PMID- 19841444
TI  - ACP Journal Club. Minimally invasive and conventional glucose monitoring did not
      differ for long-term glycemic control in insulin-treated diabetes.

PMID- 19841445
TI  - ACP Journal Club. Rosiglitazone was noninferior to metformin plus sulfonylurea
      for CV events but increased risk for HF and fractures in type 2 diabetes.

PMID- 19841446
TI  - ACP Journal Club. Graduated compression stockings did not prevent deep venous
      thrombosis after stroke and increased skin complications.

PMID- 19841447
TI  - ACP Journal Club. Review: Evidence for the effectiveness of nonsurgical
      interventions for low back pain and radiculopathy is limited.

PMID- 19841448
TI  - ACP Journal Club. Review: Evidence for the effectiveness of surgery for low back
      pain, radiculopathy, and spinal stenosis is limited.

PMID- 19841449
TI  - ACP Journal Club. Quadrivalent HPV vaccine reduced risk for HPV infection and
      related disease in women 24 to 45 years of age.

PMID- 19841450
TI  - ACP Journal Club. Review: Amiodarone reduces risk for sudden cardiac death but
      not all-cause mortality in cardiomyopathy.

PMID- 19841451
TI  - ACP Journal Club. Review: Statins reduce mortality and cardiovascular events in
      adults at risk for cardiovascular disease.

PMID- 19841452
TI  - ACP Journal Club. Contrast-enhanced magnetic resonance angiography is the most
      accurate noninvasive imaging technique for carotid stenosis.

PMID- 19841453
TI  - Effect of fluticasone with and without salmeterol on pulmonary outcomes in
      chronic obstructive pulmonary disease: a randomized trial.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists
      (LABAs) are used to treat moderate to severe chronic obstructive pulmonary
      disease (COPD). OBJECTIVE: To determine whether long-term ICS therapy, with and
      without LABAs, reduces inflammation and improves pulmonary function in COPD.
      DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration
      number: NCT00158847) SETTING: 2 university medical centers in The Netherlands.
      PATIENTS: 114 steroid-naive current or former smokers with moderate to severe
      COPD. MEASUREMENTS: Cell counts in bronchial biopsies and sputum (primary
      outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical
      outcomes every 3 months. INTERVENTION: Random assignment by minimization method
      to receive fluticasone propionate, 500 microg twice daily, for 6 months (n = 31)
      or 30 months (n = 26); fluticasone, 500 microg twice daily, and salmeterol, 50
      microg twice daily, for 30 months (single inhaler; n = 28); or placebo twice
      daily (n = 29). RESULTS: 101 patients were greater than 70% adherent to therapy.
      Fluticasone therapy decreased counts of mucosal CD3(+) cells (-55% [95% CI, -74%
      to -22%]; P = 0.004), CD4(+) cells (-78% [CI, -88% to 60%]; P < 0.001), CD8(+)
      cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to 
      2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6
      months, with effects maintained after 30 months. Fluticasone therapy for 30
      months reduced mast cell count and increased eosinophil count and percentage of
      intact epithelium, with accompanying reductions in sputum neutrophil, macrophage,
      and lymphocyte counts and improvements in FEV(1) decline, dyspnea, and quality of
      life. Reductions in inflammatory cells correlated with clinical improvements.
      Discontinuing fluticasone therapy at 6 months increased counts of CD3(+) cells
      (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P <
      0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical
      outcome. Adding salmeterol improved FEV(1) level. LIMITATIONS: The study was not
      designed to evaluate clinical outcomes. Measurement of primary outcome was not
      available for 24% of patients at 30 months. CONCLUSION: ICS therapy decreases
      inflammation and can attenuate decline in lung function in steroid-naive patients
      with moderate to severe COPD. Adding LABAs does not enhance these effects. .

PMID- 19841454
TI  - Collaborative meta-analysis: associations of 150 candidate genes with
      osteoporosis and osteoporotic fracture.
AB  - BACKGROUND: Osteoporosis is a highly heritable trait. Many candidate genes have
      been proposed as being involved in regulating bone mineral density (BMD). Few of
      these findings have been replicated in independent studies. OBJECTIVE: To assess
      the relationship between BMD and fracture and all common single-nucleotide
      polymorphisms (SNPs) in previously proposed osteoporosis candidate genes. DESIGN:
      Large-scale meta-analysis of genome-wide association data. SETTING: 5
      international, multicenter, population-based studies. PARTICIPANTS: Data on BMD
      were obtained from 19 195 participants (14 277 women) from 5 populations of
      European origin. Data on fracture were obtained from a prospective cohort (n =
      5974) from the Netherlands. MEASUREMENTS: Systematic literature review using the
      Human Genome Epidemiology Navigator identified autosomal genes previously
      evaluated for association with osteoporosis. We explored the common SNPs arising
      from the haplotype map of the human genome (HapMap) across all these genes. BMD
      at the femoral neck and lumbar spine was measured by dual-energy x-ray
      absorptiometry. Fractures were defined as clinically apparent, site-specific,
      validated nonvertebral and vertebral low-energy fractures. RESULTS: 150 candidate
      genes were identified and 36 016 SNPs in these loci were assessed. SNPs from 9
      gene loci (ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and
      TNFSF11) were associated with BMD at either site. For most genes, no SNP was
      statistically significant. For statistically significant SNPs (n = 241), effect
      sizes ranged from 0.04 to 0.18 SD per allele. SNPs from the LRP5, SOST, SPP1, and
      TNFRSF11A loci were significantly associated with fracture risk; odds ratios
      ranged from 1.13 to 1.43 per allele. These effects on fracture were partially
      independent of BMD at SPP1 and SOST. LIMITATION: Only common polymorphisms in
      linkage disequilibrium with SNPs in HapMap could be assessed, and previously
      reported associations for SNPs in some candidate genes could not be excluded.
      CONCLUSION: In this large-scale collaborative genome-wide meta-analysis, 9 of 150
      candidate genes were associated with regulation of BMD, 4 of which also
      significantly affected risk for fracture. However, most candidate genes had no
      consistent association with BMD.

PMID- 19841456
TI  - Risk for hospital contact with infection in patients with splenectomy: a
      population-based cohort study.
AB  - BACKGROUND: Splenectomy has been associated with increased risk for infection.
      OBJECTIVE: To assess the magnitude and duration of risk for hospital contact with
      infection associated with splenectomy. DESIGN: Population-based cohort study.
      SETTING: Denmark. PATIENTS: All 3812 persons in Denmark who underwent splenectomy
      from 1996 to 2005. Splenectomized patients were matched to 3 comparison cohorts:
      the general population, appendectomized patients, and unsplenectomized patients
      with indications for splenectomy. MEASUREMENTS: Relative risks were assessed for
      hospital contact involving any infection, pneumonia, and microbiologically
      confirmed bacteremia among 3812 splenectomized patients and their matched
      comparisons, during different follow-up periods and after regression analysis for
      confounder adjustment. RESULTS: The adjusted relative risk for any hospital
      contact with infection was highest within 90 days of splenectomy: 10.2% vs. 0.6%
      among general population comparisons (adjusted odds ratio, 18.1 [95% CI, 14.8 to
      22.1]) and 10.2% vs. 4.2% among appendectomized patients (adjusted odds ratio,
      2.4 [CI, 2.1 to 2.8]). The hazard of infection was 4.6-fold (CI, 3.8 to 5.5)
      higher in splenectomized patients than in general population comparisons from 91
      to 365 days after splenectomy and 2.5 times (CI, 2.2 to 2.8) higher more than 365
      days after splenectomy. The risks were similar for pneumonia and were higher for
      bacteremia. Markedly increased risks were also found when compared with those of
      appendectomized patients. Modest increases in infection risk were seen with
      splenectomy matched-indication comparisons (adjusted 90-day odds ratio, 1.7 [CI,
      1.5 to 2.1]; hazard ratios, 1.5 [CI, 1.2 to 1.8] from 91 to 365 days after
      splenectomy and 1.2 [CI, 1.1 to 1.4] beyond 365 days after splenectomy). Relative
      risks for infection were highest in patients who had splenectomy because of
      hematologic disorders. LIMITATION: Increased surveillance among splenectomized
      patients may have affected the findings. CONCLUSION: Splenectomy is associated
      with increased long-term risk for infections involving hospital contact.

PMID- 19841455
TI  - Cost-effectiveness of human papillomavirus vaccination and cervical cancer
      screening in women older than 30 years in the United States.
AB  - BACKGROUND: Women older than 30 years are the main beneficiaries of improved
      cervical cancer screening with human papillomavirus (HPV) DNA testing. The role
      of vaccination against HPV types 16 and 18, which is recommended routinely for
      preadolescent girls, is unclear in this age group. OBJECTIVE: To assess the
      health and economic outcomes of HPV vaccination in older U.S. women. DESIGN: Cost
      effectiveness analysis with an empirically calibrated model. DATA SOURCES:
      Published literature. TARGET POPULATION: U.S. women aged 35 to 45 years. TIME
      HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: HPV vaccination added to
      screening strategies that differ by test (cytology or HPV DNA testing),
      frequency, and start age versus screening alone. OUTCOME MEASURES: Incremental
      cost-effectiveness ratios (2006 U.S. dollars per quality-adjusted life-year
      [QALY] gained). RESULTS OF BASE-CASE ANALYSIS: In the context of annual or
      biennial screening, HPV vaccination of women aged 35 to 45 years ranged from $116
      950 to $272 350 per QALY for cytology with HPV DNA testing for triage of
      equivocal results and from $193 690 to $381 590 per QALY for combined cytology
      and HPV DNA testing, depending on age and screening frequency. RESULTS OF
      SENSITIVITY ANALYSIS: The probability of HPV vaccination being cost-effective for
      women aged 35 to 45 years was 0% with annual or biennial screening and less than
      5% with triennial screening, at thresholds considered good value for money.
      LIMITATION: The natural history of the disease and the efficacy of the vaccine in
      older women are uncertain. CONCLUSION: Given currently available information, the
      effectiveness of HPV vaccination for women older than 30 years who are screened
      seems to be small. Compared with current screening that uses sensitive HPV DNA
      testing, HPV vaccination is associated with less attractive cost-effectiveness
      ratios in this population than those for other, well-accepted interventions in
      the United States.

PMID- 19841457
TI  - Meta-analysis: ventilation strategies and outcomes of the acute respiratory
      distress syndrome and acute lung injury.
AB  - BACKGROUND: Trials have provided conflicting results regarding the effect of
      different ventilatory strategies on the outcomes of patients with the acute
      respiratory distress syndrome (ARDS) and acute lung injury. PURPOSE: To determine
      whether ventilation with low tidal volume (Vt) and limited airway pressure or
      higher positive end-expiratory pressure (PEEP) improves outcomes for patients
      with ARDS or acute lung injury. DATA SOURCES: Multiple computerized databases
      (through March 2009), reference lists of identified articles, and queries of
      principal investigators. No language restrictions were applied. STUDY SELECTION:
      Randomized, controlled trials (RCTs) reporting mortality and comparing lower
      versus higher Vt ventilation, lower versus higher PEEP, or a combination of both
      in adults with ARDS or acute lung injury. DATA EXTRACTION: Using a standard
      protocol, 2 reviewer teams assessed trial eligibility and abstracted data on
      quality of study design and conduct, population characteristics, intervention, co
      interventions, and confounding variables. DATA SYNTHESIS: 4 RCTs tested lower
      versus higher Vt ventilation at similar PEEP in 1149 patients, 3 RCTs compared
      lower versus higher PEEP at low Vt ventilation in 2299 patients, and 2 RCTs
      compared a combination of higher Vt and lower PEEP ventilation versus lower Vt
      and higher PEEP ventilation in 148 patients. Lower Vt ventilation reduced
      hospital mortality (odds ratio, 0.75 [95% CI, 0.58 to 0.96]; P = 0.02) compared
      with higher Vt ventilation at similar PEEP. Higher PEEP did not reduce hospital
      mortality (odds ratio, 0.86 [CI, 0.72 to 1.02]; P = 0.08) compared with lower
      PEEP using low Vt ventilation. Higher PEEP reduced the need for rescue therapy to
      prevent life-threatening hypoxemia (odds ratio, 0.51 [CI, 0.36 to 0.71]; P <
      0.001) and death (odds ratio, 0.51 [CI, 0.36 to 0.71]; P < 0.001) in patients
      receiving rescue therapies. LIMITATIONS: Pooling according to similar ventilatory
      strategies resulted in few RCTs analyzed in each group. The benefit of low Vt is
      derived from only 1 study. CONCLUSION: Available evidence from a limited number
      of RCTs shows better outcomes with routine use of low Vt but not high PEEP
      ventilation in unselected patients with ARDS or acute lung injury. High PEEP may
      help to prevent life-threatening hypoxemia in selected patients.

PMID- 19841458
TI  - Medicine as ecoculture.
AB  - The use of diagnostic tests, especially imaging studies, varies markedly across
      the United States-with higher costs but no better patient outcomes associated
      with the highest-use regions. A proposed new model of the health care system
      draws on an analogy with the ecosystem to explain the geographic variations in
      physician test ordering. This framework emphasizes the adaptability and
      interdependence of the components of the system. Patients and physicians are
      influenced by the health care organizations in their community, including the
      practice site in which the physician works, local hospitals, malpractice lawyers,
      and imaging centers. These are in turn influenced by institutions in society at
      large, including the media, health care plans, and the government. Further
      adaptations to the explanatory model account for the psychologic and sociologic
      aspects of physician behavior. Understanding the medical ecoculture is essential
      for effective health care reform because widely touted changes, such as the
      introduction of an electronic medical record or comparative effectiveness
      studies, do not address the adaptability and interdependence that characterize
      the medical ecoculture.

PMID- 19841459
TI  - Identification of osteoporosis risk genes: the tip of the iceberg.

PMID- 19841460
TI  - Lovenox hurts.

PMID- 19841461
TI  - Responses to USPSTF guideline on aspirin for prevention of cardiovascular
      disease.

PMID- 19841462
TI  - Responses to USPSTF guideline on aspirin for prevention of cardiovascular
      disease.

PMID- 19841463
TI  - Missed opportunities in the trial on proton-pump inhibitor therapy in bleeding
      peptic ulcers.

PMID- 19841464
TI  - Missed opportunities in the trial on proton-pump inhibitor therapy in bleeding
      peptic ulcers.

PMID- 19841465
TI  - Missed opportunities in the trial on proton-pump inhibitor therapy in bleeding
      peptic ulcers.

PMID- 19841466
TI  - Universal insurance coverage and health care inequity.

PMID- 19841467
TI  - Inappropriate diagnosis and chelation treatment of alleged heavy-metal toxicity.

PMID- 19841468
TI  - Successful identification of glycine transporter inhibitors using an adaptation
      of a functional cell-based assay.
AB  - Glycine transporter (GlyT1) function is typically measured by radiolabeled
      glycine uptake using lysis methods or scintillation proximity assays (SPAs),
      which have limited throughput. This study shows the adaptation of the standard
      cell lysis method to a screening assay with improved throughput and assay
      characteristics. The assay takes advantage of the 384-well format, standard
      laboratory automation, and cryopreserved CHO-K1 cells stably overexpressing human
      GlyT1a transporter (CHO-K1/hGlyT1a) that were validated and banked in advance of
      screening. The assay was evaluated for the time course of glycine uptake, K(m),
      V(max), Z' factor analysis, and IC(50) value determination with reference GlyT1
      inhibitors. Screening of 118,000 compounds at 10 microM identified 4556 compounds
      (3.9%) as inhibitors. Positive compounds (>50% inhibition) were retested in the
      assay at 4 inhibitor concentrations. Compounds demonstrating greater than 40%
      inhibition at 10 microM were considered as confirmed positives, yielding a 68%
      confirmation rate from the original screen. To eliminate compounds that
      nonspecifically inhibited glycine uptake, IC(50) values were determined in both
      GlyT1 and GlyT2 assays, and those compounds that inhibited GlyT2 were removed
      from consideration. The screening campaign identified 300 small molecules as
      selective GlyT1 inhibitors for lead optimization, demonstrating the utility of
      this cost-effective method.

PMID- 19841469
TI  - Storage of cord blood.

PMID- 19841470
TI  - Sublethal doses of an anti-erbB2 antibody leads to death by apoptosis in
      cardiomyocytes sensitized by low prosenescent doses of epirubicin: the protective
      role of dexrazoxane.
AB  - The cardiotoxic synergism resulting from the sequential treatment with
      anthracyclines and trastuzumab has been attributed to the trastuzumab-induced
      loss of the erbB2-related functions that serve as a salvage pathway against the
      damaging effects of anthracyclines. Cellular senescence is a novel mechanism of
      cardiotoxicity induced by subapoptotic doses of anthracyclines. After having
      identified prosenescent and proapoptotic doses of epirubicin and rat MAb c
      erbB2/Her-2/neu Ab-9 clone B10 (B10), an anti-erbB2 monoclonal antibody, we
      investigated the effects of the sequential treatment with prosenescent doses of
      both drugs on H9c2 cells and neonatal rat cardiomyocytes pretreated with or
      without the cardioprotective agent dexrazoxane. Cells were analyzed by senescence
      associated beta-galactosidase, single-stranded DNA, annexin/propidium double
      staining, F-actin, and mitochondrial transmembrane potential. ErbB2 expression
      levels, AKT activation, and the effects of the inhibition of nicotinamide adenine
      dinucleotide phosphate oxidase [NAD(P)H oxidase] and phosphoinositide-3-OH kinase
      (PI3K) were also assessed. Data demonstrate that 1) the toxic effects of
      epirubicin mainly occur through NAD(P)H oxidase activation; 2) the erbB2
      overexpression induced by epirubicin is a redox-sensitive mechanism largely
      dependent on NAD(P)H oxidase; 3) the loss of erbB2-related functions caused by
      B10 determines marginal cellular changes in untreated cells, but causes massive
      death by apoptosis in cells previously exposed to a prosenescent dose of
      epirubicin, 4) dexrazoxane promotes survival pathways, as demonstrated by the
      activation of Akt and the PI3K-dependent erbB2 overexpression; and 5) it also
      prevents epirubicin-induced senescence and renders epirubicin-treated cells more
      resistant to treatment with B10. Data underline the importance of NAD(P)H oxidase
      in epirubicin-induced cardiotoxicity and shed new light on the protective
      mechanisms of dexrazoxane.

PMID- 19841471
TI  - Cyanide-induced apoptosis of dopaminergic cells is promoted by BNIP3 and Bax
      modulation of endoplasmic reticulum-mitochondrial Ca2+ levels.
AB  - Cyanide is a potent neurotoxicant that can produce dopaminergic neuronal death in
      the substantia nigra and is associated with a Parkinson-like syndrome. In this
      study involvement of Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a
      BH3-only Bcl-2 protein, in cyanide-induced death of dopaminergic cells was
      determined in mice and Mes 23.5 cells. Treatment of mice with cyanide up
      regulated BNIP3 and Bax expression in tyrosine hydroxylase (TH)-positive cells of
      the substantia nigra, and progressive loss of TH-positive neurons was observed
      over a 9-day period. In Mes 23.5 dopaminergic cells, cyanide stimulated
      translocalization of BNIP3 to both endoplasmic reticulum (ER) and mitochondria.
      In ER, BNIP3 stimulated release of Ca(2+) into the cytosol, followed by
      accumulation of mitochondrial Ca(2+), resulting in reduction of mitochondrial
      membrane potential (Deltapsi(m)) and eventually cell death. Cyanide also
      activated Bax to colocalize with BNIP3 in ER and mitochondria. Forced
      overexpression of BNIP3 activated Bax, whereas gene silencing reduced Bax
      activity. Knockdown of Bax expression by small interfering RNA blocked the BNIP3
      mediated changes in ER and mitochondrial Ca(2+) to block cyanide-induced
      mitochondrial dysfunction and cell death. These findings show that BNIP3-mediates
      cyanide-induced dopaminergic cell death through a Bax downstream signal that
      mobilizes ER Ca(2+) stores, followed by mitochondrial Ca(2+) overload.

PMID- 19841472
TI  - 20-hydroxy-5,8,11,14-eicosatetraenoic acid mediates endothelial dysfunction via
      IkappaB kinase-dependent endothelial nitric-oxide synthase uncoupling.
AB  - Endothelial dysfunction and activation occur in the vasculature and are believed
      to contribute to the pathogenesis of cardiovascular diseases. We have shown that
      20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a cytochrome P450 4A
      derived eicosanoid that promotes vasoconstriction in the microcirculation,
      uncouples endothelial nitric-oxide synthase (eNOS) and reduces nitric oxide (NO)
      levels via the dissociation of the 90-kDa heat shock protein (HSP90) from eNOS.
      It also causes endothelial activation by stimulating nuclear factor-kappaB (NF
      kappaB) and increasing levels of pro-inflammatory cytokines. In this study, we
      examined signaling mechanisms that may link 20-HETE-induced endothelial
      dysfunction and activation. Under conditions in which 20-HETE inhibited NO
      production, it also stimulated inhibitor of NF-kappaB (IkappaB) phosphorylation.
      Both effects were prevented by inhibition of tyrosine kinases and mitogen
      activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). It
      is noteworthy that inhibitor of IkappaB kinase (IKK) activity negated the 20-HETE
      mediated inhibition of NO production. Immunoprecipitation experiments revealed
      that treatment of ionophore-stimulated cells with 20-HETE brings about a decrease
      in HSP90-eNOS association and an increase in HSP90-IKKbeta association,
      suggesting that the activation by 20-HETE of NF-kappaB is linked to its action on
      eNOS. Furthermore, addition of inhibitors of tyrosine kinase MAPK and IKK
      restored the 20-HETE-mediated impairment of acetylcholine-induced relaxation in
      rat renal interlobar arteries. The results indicate that 20-HETE mediates eNOS
      uncoupling and endothelial dysfunction via the activation of tyrosine kinase,
      MAPK, and IKK, and these effects are linked to 20-HETE-mediated endothelial
      activation.

PMID- 19841473
TI  - Endogenous nitric oxide contributes to bradykinin-stimulated glucose uptake but
      attenuates vascular tissue-type plasminogen activator release.
AB  - Bradykinin causes vasodilation, stimulates tissue-type plasminogen activator (t
      PA) release and, in rodents, increases muscle glucose uptake. Although bradykinin
      causes vasodilation partly by activating nitric-oxide synthase (NOS), the role of
      nitric oxide in regulating bradykinin-stimulated t-PA release is uncertain. This
      study examined the effect of high-dose NOS inhibition on bradykinin-stimulated t
      PA release and glucose uptake in humans. We studied 24 healthy (12 women and 12
      men), overweight and obese (body mass index >25 kg/m(2)), normotensive,
      nondiabetic subjects with normal cholesterol. We measured the effect of intra
      arterial N(omega)-monomethyl-L-arginine (L-NMMA, 12 micromol/min) on forearm
      blood flow (FBF), net t-PA release, and glucose uptake at baseline and in
      response to intra-arterial bradykinin (50-200 ng/min) in subjects pretreated with
      the cyclooxygenase inhibitor aspirin. Measurements were repeated after isosorbide
      dinitrate (ISDN; 5 mg) or sildenafil (50 mg). L-NMMA decreased baseline FBF (P <
      0.001), increased baseline forearm vascular resistance (P < 0.001), and increased
      the t-PA arterial-venous gradient (P = 0.04) without affecting baseline net t-PA
      release or glucose uptake. During L-NMMA, ISDN tended to decrease baseline net t
      PA release (P = 0.06). L-NMMA blunted bradykinin-stimulated vasodilation (P <
      0.001 for FBF and FVR). Bradykinin increased net glucose extraction (from -80 +/-
      23 to -320 +/- 97 microg/min/100 ml at 200 ng/min bradykinin, P = 0.02), and L
      NMMA (-143 +/- 50 microg/min/100 ml at 200 ng/min, P = 0.045) attenuated this
      effect. In contrast, L-NMMA enhanced bradykinin-stimulated t-PA release (39.9 +/-
      7.0 ng/min/100 ml versus 30.0 +/- 4.2 ng/min/100 ml at 200 ng/min, P = 0.04 for L
      NMMA). In gender-stratified analyses, L-NMMA significantly increased bradykinin
      stimulated t-PA release in women (F = 6.7, P = 0.02) but not in men. Endogenous
      NO contributes to bradykinin-stimulated vasodilation and glucose uptake but
      attenuates the fibrinolytic response to exogenous bradykinin.

PMID- 19841475
TI  - A conserved motif in the membrane proximal C-terminal tail of human muscarinic m1
      acetylcholine receptors affects plasma membrane expression.
AB  - We investigated the functional role of a conserved motif, F(x)(6)LL, in the
      membrane proximal C-tail of the human muscarinic M(1) (hM(1)) receptor. By use of
      site-directed mutagenesis, several different point mutations were introduced into
      the C-tail sequence (423)FRDTFRLLL(431). Wild-type and mutant hM(1) receptors
      were transiently expressed in Chinese hamster ovary cells, and the amount of
      plasma membrane-expressed receptor was determined by use of intact, whole-cell
      [(3)H]N-methylscopolamine binding assays. The plasma membrane expression of hM(1)
      receptors possessing either L430A or L431A or both point mutations was
      significantly reduced compared with the wild type. The hM(1) receptor possessing
      a L430A/L431A double-point mutation was retained in the endoplasmic reticulum
      (ER), and atropine treatment caused the redistribution of the mutant receptor
      from the ER to the plasma membrane. Atropine treatment also caused an increase in
      the maximal response and potency of carbachol-stimulated phosphoinositide
      hydrolysis elicited by the L430A/L431A mutant. The effect of atropine on the
      L430A/L431A receptor mutant suggests that L(430) and L(431) play a role in
      folding hM(1) receptors, which is necessary for exit from the ER. Using site
      directed mutagenesis, we also identified amino acid residues at the base of
      transmembrane-spanning domain 1 (TM1), V(46) and L(47), that, when mutated,
      reduce the plasma membrane expression of hM(1) receptors in an atropine
      reversible manner. Overall, these mutagenesis data show that amino acid residues
      in the membrane-proximal C-tail and base of TM1 are necessary for hM(1) receptors
      to achieve a transport-competent state.

PMID- 19841474
TI  - Pharmacological characterization of human incretin receptor missense variants.
AB  - Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide
      (GIP) are gut-derived incretin hormones that regulate blood glucose levels. In
      addition to their widely accepted insulinotropic role, there is evidence that GLP
      1 modulates feeding behavior and GIP regulates lipid metabolism, thereby
      promoting postprandial fat deposition. In this study, we investigated whether
      naturally occurring polymorphisms in the GLP-1 receptor (GLP-1R) and the GIP
      receptor (GIP-R) affect the pharmacological properties of these proteins. After
      transient expression of the receptors in human embryonic kidney 293 cells, basal
      and ligand-induced cAMP production were assessed by use of luciferase reporter
      gene assays. Our data reveal that the wild-type GIP-R displays a considerable
      degree of ligand-independent activity. In comparison, the GIP-R variants C46S,
      G198C, R316L, and E354Q show a marked decrease in basal signaling that may, at
      least in part, be explained by reduced cell surface expression. When stimulated
      with GIP, the C46S and R316L mutants display significantly reduced potency (>1000
      and 25- fold, respectively) compared with wild type. Complementary competition
      binding assays further demonstrate that the C46S variant fails to bind radio
      iodinated GIP, whereas all other GIP-R mutants maintain normal ligand affinity.
      In contrast to the GIP-R, the wild-type GLP-1R lacks constitutive activity.
      Furthermore, none of the 10 GLP-1R missense mutations showed an alteration in
      pharmacological properties versus wild type. The extent to which abnormalities in
      GIP-R function may lead to physiological changes or affect drug sensitivity in
      selected populations (e.g., obese, diabetic individuals) remains to be further
      investigated.

PMID- 19841476
TI  - Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for
      the treatment of insomnia.
AB  - 5-Hydroxytryptamine (5-HT)(2A) receptor inverse agonists are promising
      therapeutic agents for the treatment of sleep maintenance insomnias. Among these
      agents is nelotanserin, a potent, selective 5-HT(2A) inverse agonist. Both
      radioligand binding and functional inositol phosphate accumulation assays suggest
      that nelotanserin has low nanomolar potency on the 5-HT(2A) receptor with at
      least 30- and 5000-fold selectivity compared with 5-HT(2C) and 5-HT(2B)
      receptors, respectively. Nelotanserin dosed orally prevented (+/-)-1-(2,5
      dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 5-HT(2A) agonist)-induced
      hypolocomotion, increased sleep consolidation, and increased total nonrapid eye
      movement sleep time and deep sleep, the latter marked by increases in
      electroencephalogram (EEG) delta power. These effects on rat sleep were
      maintained after repeated subchronic dosing. In healthy human volunteers,
      nelotanserin was rapidly absorbed after oral administration and achieved maximum
      concentrations 1 h later. EEG effects occurred within 2 to 4 h after dosing, and
      were consistent with vigilance-lowering. A dose response of nelotanserin was
      assessed in a postnap insomnia model in healthy subjects. All doses (up to 40 mg)
      of nelotanserin significantly improved measures of sleep consolidation, including
      decreases in the number of stage shifts, number of awakenings after sleep onset,
      microarousal index, and number of sleep bouts, concomitant with increases in
      sleep bout duration. Nelotanserin did not affect total sleep time, or sleep onset
      latency. Furthermore, subjective pharmacodynamic effects observed the morning
      after dosing were minimal and had no functional consequences on psychomotor
      skills or memory. These studies point to an efficacy and safety profile for
      nelotanserin that might be ideally suited for the treatment of sleep maintenance
      insomnias.

PMID- 19841478
TI  - The efficacy of vagus nerve stimulation in intractable epilepsy associated with
      nonketotic hyperglycinemia in two children.
AB  - Nonketotic hyperglycinemia is an inborn error of glycine metabolism and these
      patients frequently suffer from intractable epilepsy despite treatment with
      sodium benzoate, dextromethophan, and multiple anticonvulsants. We encountered 2
      infants with nonketotic hyperglycinemia whose intractable generalized convulsive
      seizures were difficult to control with sodium benzoate, dextromethophan, and
      multiple anticonvulsants. However, after the addition of vagus nerve stimulation,
      their intractable generalized seizures were >75% reduced in frequency, the
      numbers of multiple anticonvulsants were reduced, and the quality of life
      significantly improved. The efficacy in seizure reduction persists for at least 3
      years in both children.

PMID- 19841477
TI  - Myb-induced chromatin remodeling at a dual enhancer/promoter element involves non
      coding rna transcription and is disrupted by oncogenic mutations of v-myb.
AB  - The oncogene v-myb of avian myeloblastosis virus (AMV) encodes a transcription
      factor (v-Myb) that transforms myelomonocytic cells by deregulating the
      expression of specific target genes. v-myb has acquired its oncogenic potential
      by truncation as well as by a number of point mutations of its cellular
      progenitor c-myb. As a result of these changes, the target gene spectrum v-Myb
      differs from that of c-Myb. We recently showed that the chicken mim-1 gene, a c
      Myb target gene that is not activated by v-Myb harbors a powerful cell type
      specific and Myb-inducible enhancer in addition to a Myb-responsive promoter. We
      now show that Myb-dependent activation of the mim-1 gene is accompanied by
      extensive remodeling of the nucleosomal architecture at the enhancer. We found
      that the mim-1 enhancer region also harbors a promoter whose activity is
      stimulated by Myb and which directs the transcription of an apparently non-coding
      RNA. Furthermore, our data show that the oncogenic mutations of AMV have
      disrupted the ability of v-Myb to induce remodeling of chromatin structure at the
      mim-1 enhancer. Together, our results demonstrate for the first time directly
      that Myb induces alterations of the nucleosomal organization at a relevant target
      site and provide new insight into the functional consequences of the oncogenic
      amino acid substitutions.

PMID- 19841479
TI  - Identification of SMARCAL1 as a component of the DNA damage response.
AB  - SMARCAL1 (also known as HARP) is a SWI/SNF family protein with an ATPase activity
      stimulated by DNA containing both single-stranded and double-stranded regions.
      Mutations in SMARCAL1 are associated with the disease Schimke immuno-osseous
      dysplasia, a multisystem autosomal recessive disorder characterized by T cell
      immunodeficiency, growth inhibition, and renal dysfunction. The cellular function
      of SMARCAL1, however, is unknown. Here, using Xenopus egg extracts and mass
      spectrometry, we identify SMARCAL1 as a protein recruited to double-stranded DNA
      breaks. SMARCAL1 binds to double-stranded breaks and stalled replication forks in
      both egg extract and human cells, specifically colocalizing with the single
      stranded DNA binding factor RPA. In addition, SMARCAL1 interacts physically with
      RPA independently of DNA. SMARCAL1 is phosphorylated in a caffeine-sensitive
      manner in response to double-stranded breaks and stalled replication forks. It
      has been suggested that stalled forks can be stabilized by a mechanism involving
      caffeine-sensitive kinases, or they collapse and subsequently recruit Rad51 to
      promote homologous recombination repair. We show that depletion of SMARCAL1 from
      U2OS cells leads to increased frequency of RAD51 foci upon generation of stalled
      replication forks, indicating that fork breakdown is more prevalent in the
      absence of SMARCAL1. We propose that SMARCAL1 is a novel DNA damage-binding
      protein involved in replication fork stabilization.

PMID- 19841480
TI  - Rapid exchange of bound ADP on the Staphylococcus aureus replication initiation
      protein DnaA.
AB  - In Escherichia coli, regulatory inactivation of the replication initiator DnaA
      occurs after initiation as a result of hydrolysis of bound ATP to ADP, but it has
      been unknown how DnaA is controlled to coordinate cell growth and chromosomal
      replication in gram-positive bacteria such as Staphylococcus aureus. This study
      examined the roles of ATP binding and its hydrolysis in the regulation of the S.
      aureus DnaA activity. In vitro, S. aureus DnaA melted S. aureus oriC in the
      presence of ATP but not ADP by a mechanism independent of ATP hydrolysis. Unlike
      E. coli DnaA, binding of ADP to S. aureus DnaA was unstable. As a result, at
      physiological concentrations of ATP, ADP bound to S. aureus DnaA was rapidly
      exchanged for ATP, thereby regenerating the ability of DnaA to form the open
      complex in vitro. Therefore, we examined whether formation of ADP-DnaA
      participates in suppression of replication initiation in vivo. Induction of the
      R318H mutant of the AAA+ sensor 2 protein, which has decreased intrinsic ATPase
      activity, caused over-initiation of chromosome replication in S. aureus,
      suggesting that formation of ADP-DnaA suppresses the initiation step in S.
      aureus. Together with the biochemical features of S. aureus DnaA, the weak
      ability to convert ATP-DnaA into ADP-DnaA and the instability of ADP-DnaA, these
      results suggest that there may be unidentified system(s) for reducing the
      cellular ratio of ATP-DnaA to ADP-DnaA in S. aureus and thereby delaying the re
      initiation of DNA replication.

PMID- 19841482
TI  - Early recognition of critically ill patients.

PMID- 19841483
TI  - Early identification of patients with or at risk of acute lung injury.
AB  - Acute lung injury (ALI ) and its more severe form, acute respiratory distress
      syndrome (ARDS ), are important critical care syndromes for which the treatment
      options are limited once the condition is fully established. Enormous basic and
      clinical research efforts have led to improvements in supportive treatment, but
      surprisingly little has been done on the prevention of this devastating syndrome.
      The development and progression of ALI /ARDS may be triggered by various
      intrahospital exposures including but not limited to transfusion, aspiration,
      mechanical ventilation, certain medications and delayed treatment of shock and
      infection. Early recognition of patients with or at risk of ALI /ARDS is
      essential for designing novel prevention and treatment strategies. Automated
      electronic screening tools and novel scoring systems applied at the time of
      hospital admission may facilitate enrollment of patients into mechanistic and
      outcome studies, as well as future ALI /ARDS prevention trials.

PMID- 19841481
TI  - NTE1-encoded phosphatidylcholine phospholipase b regulates transcription of
      phospholipid biosynthetic genes.
AB  - The Saccharomyces cerevisiae NTE1 gene encodes an evolutionarily conserved
      phospholipase B localized to the endoplasmic reticulum (ER) that degrades
      phosphatidylcholine (PC) generating glycerophosphocholine and free fatty acids.
      We show here that the activity of NTE1-encoded phospholipase B (Nte1p) prevents
      the attenuation of transcription of genes encoding enzymes involved in
      phospholipid synthesis in response to increased rates of PC synthesis by
      affecting the nuclear localization of the transcriptional repressor Opi1p. Nte1p
      activity becomes necessary for cells growing in inositol-free media under
      conditions of high rates of PC synthesis elicited by the presence of choline at
      37 degrees C. The specific choline transporter encoded by the HNM1 gene is
      necessary for the burst of PC synthesis observed at 37 degrees C as follows: (i)
      Nte1p is dispensable in an hnm1Delta strain under these conditions, and (ii)
      there is a 3-fold increase in the rate of choline transport via the Hnm1p choline
      transporter upon a shift to 37 degrees C. Overexpression of NTE1 alleviated the
      inositol auxotrophy of a plethora of mutants, including scs2Delta, scs3Delta,
      ire1Delta, and hac1Delta among others. Overexpression of NTE1 sustained
      phospholipid synthesis gene transcription under conditions that normally repress
      transcription. This effect was also observed in a strain defective in the
      activation of free fatty acids for phosphatidic acid synthesis. No changes in the
      levels of phosphatidic acid were detected under conditions of altered expression
      of NTE1. Consistent with a synthetic impairment between challenged ER function
      and inositol deprivation, increased expression of NTE1 improved the growth of
      cells exposed to tunicamycin in the absence of inositol. We describe a new role
      for Nte1p toward membrane homeostasis regulating phospholipid synthesis gene
      transcription. We propose that Nte1p activity, by controlling PC abundance at the
      ER, affects lateral membrane packing and that this parameter, in turn, impacts
      the repressing transcriptional activity of Opi1p, the main regulator of
      phospholipid synthesis gene transcription.

PMID- 19841484
TI  - Rhabdomyolysis: a review of the literature.
AB  - Rhabdomyolysis is a potentially life-threatening syndrome that can develop from a
      variety of causes; the classic findings of muscular aches, weakness and tea
      coloured urine are non-specific and may not always be present. The diagnosis
      therefore rests upon the presence of a high level of suspicion of any abnormal
      laboratory values in the mind of the treating physician. An elevated plasma
      creatine kinase (CK) level is the most sensitive laboratory finding pertaining to
      muscle injury; whereas hyperkalaemia, acute renal failure and compartment
      syndrome represent the major life-threatening complications. The management of
      the condition includes prompt and aggressive fluid resuscitation, elimination of
      the causative agents and treatment and prevention of any complications that may
      ensue. The objective of this review is to describe the aetiological spectrum and
      pathophysiology of rhabdomyolysis, the clinical and biological consequences of
      this syndrome and to provide an appraisal of the current data available in order
      to facilitate the prevention, early diagnosis and prompt management of this
      condition.

PMID- 19841485
TI  - A systematic review of selective and non-selective beta blockers for prevention
      of vascular events in patients with acute coronary syndrome or heart failure.
AB  - BACKGROUND: To assess the influence of beta2-receptor suppression on top of
      selective beta1-receptor blockade on the occurrence of vascular events and on all
      cause mortality in patients with acute coronary syndrome (ACS) or heart failure
      (HF ). METHODS: Systematic review of studies published since 1980. Randomised
      controlled trials directly comparing beta1 blockers with beta1+2 blockers, or
      comparing the two beta blockers with placebo, were included. Studies had a
      minimum treatment period of three months and total mortality or vascular events
      as their primary or secondary outcome. RESULTS: Of the included studies, five
      directly compared beta blockers (3733 patients) and 28 compared beta blockers
      with placebo (30,889 patients). These latter studies were heterogeneous in study
      population, dose and type of beta blockers. In ACS, the only study directly
      comparing different beta blockers was underpowered to detect a difference on
      mortality, while in HF beta1+2 blockers significantly decreased mortality
      compared with b1 blockers (RR 0.86, 95% confidence interval 0.78 to 0.94). In
      ACS, beta1 blockers in placebo-controlled trials non-significantly reduced total
      mortality (RR 0.82, 0.67 to 1.01) or vascular events (RR 0.68, 0.42 to 1.11),
      while beta1+2 blockers were associated with a significant decrease in total
      mortality (RR 0.73, 0.64 to 0.82), and vascular events (RR 0.71, 0.59 to 0.84).
      In HF, beta1 and beta1+2 blockers reduced total mortality, while only beta1+2
      blockers decreased vascular events (RR 0.80, 0.64 to 1.00). CONCLUSIONS:
      Additional beta2-receptor blockade may be more effective than beta1-receptor
      blockade alone in preventing total mortality and vascular events in patients with
      ACS or, to a lesser extent, HF . However, only a few studies directly compared
      beta blockers, and indirect comparisons were subject to heterogeneity, which
      weakens firm conclusions.

PMID- 19841486
TI  - Heart failure as presenting manifestation of cardiac involvement in systemic
      lupus erythematosus.
AB  - BACKGROUND: Heart failure in systemic lupus erythematosus (SLE ) is rare, and its
      long-term outcome is unknown. The aim of this study was to analyse the long-term
      outcome of six SLE patients with heart failure as first manifestation of cardiac
      involvement and to review previously reported cases. METHODS: We conducted a
      retrospective chart review of SLE patients from two tertiary referral centres who
      presented between 1999 and 2004 with clinical and echocardiographic signs of
      heart failure as their first manifestation of cardiac involvement. Details of the
      clinical presentation and follow-up and serial findings at echocardiography were
      collected. A retrospective review of the literature was performed using the
      PubMed database. RESULTS: Six cases were identified who presented with heart
      failure, as confirmed by echocardiography (left ventricular ejection fraction
      (LVEF) ranging from 23 to 37%). Treatment with high-dose glucocorticoids,
      cytotoxic treatment (azathioprine in one patient, cyclophosphamide in five
      patients), intravenous immunoglobulins (in one patient) and temporary inotropic
      support (two patients) resulted in complete resolution of symptoms and
      improvement of LVEF , with a mean follow-up of 77 months (range 43 to 113).
      Twenty-one additional cases of heart failure as manifestation of cardiac
      involvement in SLE have been reported, most with favourable short-term outcome
      following institution of immunosuppressive therapy. CONCLUSIONS: Heart failure is
      a rare but life-threatening manifestation of cardiac involvement in SLE. Long
      term outcome can be excellent when aggressive treatment is instituted promptly.

PMID- 19841487
TI  - Complete remission of severe idiopathic cold urticaria on interleukin-1 receptor
      antagonist (anakinra).
AB  - A 62-year-old patient had suffered from severe cold intolerance with an
      urticarial rash and oropharyngeal angio-oedema upon cold exposure since early
      childhood. This could be provoked by the ice cube test and by exposure in a cold
      room. Her family history was negative, and she did not carry any mutations in the
      NRLP3 gene. Treatment with IL-1 receptor antagonist anakinra resulted in complete
      resolution of these symptoms, with a radical beneficial change in her quality of
      life. In recent years this patient had developed progressive neurological
      symptoms leading to a diagnosis of amyotrophic lateral sclerosis (ALS), which
      seems unrelated to the idiopathic cold urticaria. The neurological symptoms did
      not respond to anakinra treatment and were eventually fatal. CONCLUSION: We
      describe the first case of IL-1RA treatment in idiopathic cold urticaria with
      good response. Anakinra had no effect on the progression of her symptoms of ALS.

PMID- 19841488
TI  - A 72-year-old man with a rapidly progressive sepsis caused by a rare but life
      threatening infection.

PMID- 19841489
TI  - A woman with a swollen neck.

PMID- 19841490
TI  - A patient with haemolytic anaemia diagnosed after thirty years.

PMID- 19841491
TI  - Internal medicine residents' knowledge about sepsis: effects of a teaching
      intervention.
AB  - The short- and long-term effects of a single teaching intervention for internal
      medicine residents are not known. Since sepsis is a prevalent and important
      disease and both therapeutic and diagnostic interventions have been protocolized,
      we investigated the effects of a sepsis-based single teaching intervention. A
      prospective before-and-after education study was performed among residents who
      attended a regional professional training for internal medicine. All residents
      who participated were invited to complete a questionnaire about the assessment of
      symptoms and the diagnosis and treatment of sepsis. The questionnaire was filled
      out before, directly after, and four to six months after the teaching
      intervention. The overall questionnaire score was expressed on a 0 to 10 scale. A
      total of 253 questionnaires from 109 training-grade doctors were collected. At
      baseline, the 'assessment of symptoms of sepsis' score was significantly lower
      than the 'diagnosis and treatment' score. Following the education session,
      training-grade doctors' knowledge about sepsis definitions and diagnosis and
      treatment of sepsis increased from (mean +/- SD ) 6.1 +/- 1.6 to 8.2 +/- 1.2
      (p<0.0001. Moreover, four to six months after the teaching intervention, this
      effect was sustained (p<0.0001 compared with test 1), resulting in a mean score
      of 7.6 +/- 1.1. Our single teaching intervention resulted in improved and
      sustained knowledge on the assessment of symptoms, diagnosis and treatment of
      sepsis.

PMID- 19841492
TI  - Microscopic colitis and endoscopy.

PMID- 19841493
TI  - Unexpected cause of iron deficiency detected by capsule endoscopy.

PMID- 19841495
TI  - Methodology of diagnostic tests in hepatology.
AB  - The performance of diagnostic tests can be assessed by a number of methods. These
      include sensitivity, specificity,positive and negative predictive values,
      likelihood ratios and receiver operating characteristic (ROC) curves. This paper
      describes the methods and explains which information they provide. Sensitivity
      and specificity provides measures of the diagnostic accuracy of a test in
      diagnosing the condition. The positive and negative predictive values estimate
      the probability of the condition from the test-outcome and the condition's
      prevalence. The likelihood ratios bring together sensitivity and specificity and
      can be combined with the condition's pre-test prevalence to estimate the posttest
      probability of the condition. The ROC curve is obtained by calculating the
      sensitivity and specificity of a quantitative test at every possible cut-off
      point between 'normal' and 'abnormal' and plotting sensitivity as a function of 1
      specificity. The ROC-curve can be used to define optimal cut-off values for a
      test, to assess the diagnostic accuracy of the test, and to compare the
      usefulness of different tests in the same patients. Under certain conditions it
      may be possible to utilize a test's quantitative information as such (without
      dichotomization) to yield diagnostic evidence in proportion to the actual test
      value. By combining more diagnostic tests in multivariate models the diagnostic
      accuracy may be markedly improved.

PMID- 19841496
TI  - Hepatotoxicity by drugs and dietary supplements: safety perspectives on clinical
      and regulatory issues.
AB  - Hepatotoxicity by drugs and dietary supplements (DDS) is a rare and unpredictable
      event but with the risk of a life-threatening clinical course when it occurs. It
      may emerge despite intensive chemical, toxicological and observational studies
      that indicate no hepatotoxic signals. This suggests major clinical and regulatory
      issues that must be addressed in the area of accurate testing, reporting, and
      accessibility of reliable n data. Consequently, in a clinical setting, safety
      concerns are key elements in the treatment of patients, and require that the
      diagnosis of DDS hepatotoxicity clearly be established. Causality of DDS
      hepatotoxicity may be pursued using a diagnostic algorithm consisting of a pre
      test, a main-test as the scale of the updated CIOMS (Council for International
      Organizations of Medical Sciences), and a post-test. The results of these tests
      are then sent item by item to the National Health Agency, where the case will
      undergo further evaluation for pharmacovigilance, strategic aspects and safety
      issues. After this analysis, all items of the tests are included in the
      regulatory database freely accessible to the health and scientific community.
      With this diagnostic and regulatory algorithm the risk of misdiagnoses and
      inappropriate regulatory measures may be minimized and the safety improved. In
      conclusion,DDS hepatotoxicity is a rare but is a potentially life-threatening
      entity requiring a reliable diagnosis with the aid of a diagnostic algorithm, and
      a thorough pharmacovigilance evaluation by national and international health
      agencies. Safety aspects in DDS hepatotoxicity represent a major clinical and
      regulatory issue and should consequently be addressed.

PMID- 19841497
TI  - Evaluation of liver diseases in Iranian patients with primary antibody
      deficiencies.
AB  - INTRODUCTION: Patients with primary antibody deficiency (PAD) can complicate with
      liver disease. This study was performed in order to study the prevalence and
      causes of hepatobiliary diseases in Iranian patients with PAD. MATERIAL AND
      METHODS: Sixty-two patients with PAD were followed-up and signs and symptoms of
      liver disease were recorded. All patients were screened for hepatitis C virus
      (HCV-RNA) and those patients with any sign of liver disease or gastrointestinal
      complaints were tested for Cryptosporidium parvum. RESULTS: Clinical evidences of
      liver disease, including hepatomegaly, were documented in 22 patients (35.5%).
      Eight patients (13%) had clinical and/or laboratory criteria of chronic liver
      disease. Only one patient was HCV-RNA positive; he had stigmata of chronic liver
      disease and pathologic evidence of chronic active hepatitis with cirrhosis.
      Cryptosporidium parvum test was positive for one patient with hyper-IgM syndrome.
      In liver biopsy of patients with liver involvement, one had histological findings
      related to sclerosing cholangitis, and five had mild to moderate chronic active
      hepatitis with unknown reason. CONCLUSIONS: Chronic active hepatitis is the most
      common pathologic feature of liver injury in Iranian patients with PAD. Liver
      disease in PAD usually accompanies with other organ involvements and could
      increase the mortality of PAD. Whether this high rate of liver disease with
      unknown origin (75%) is the result of an unidentified hepatotropic virus or other
      mechanisms such as autoimmunity, is currently difficult to understand.

PMID- 19841498
TI  - Acute hepatitis E in Montenegro: epidemiology, clinical and laboratory features.
AB  - OBJECTIVE: To evaluate the incidence, demographic, clinical and laboratory
      characteristics of patients with acute viral hepatitis E in Montenegro. MATERIAL
      AND METHODS: A total of 400 patients with acute viral hepatitis from January 1st,
      2000 to December 31st, 2007 were enrolled in the study. Serological tests for
      hepatitis A, B, C, D, and E viruses, Epstein-Barr virus, cytomegalovirus, and
      herpes simplex viruses were performed. Standard laboratory tests for liver
      function were analyzed. The results are presented as absolute numbers, mean +/-
      SD, range of values, and percent. A P value < 0.05 was considered significant.
      RESULTS: Twenty-four (6%) patients had clinically and/or serologically confirmed
      acute hepatitis E. The mean age of the patients was 25 +/- 6 years; 62.5% were
      males. The majority of the patients (66%) belonged to the 20 to 40 yrs age group
      (P < 0.05). Seven patients were asymptomatic. Foremost symptoms were loss of
      appetite (100%), fatigue (94%) and vomiting (75%). The most frequent clinical
      sign was mild to moderate liver enlargement (94%). Jaundice had 12/17 symptomatic
      patients. Elevation of alanine aminotransferase was found in 19 patients
      including two patients without symptoms. The enzyme, gamma glutamyltranspeptidase
      was increased in all patients. CONCLUSION: Acute hepatitis E in Montenegro
      emerges as an autochthonous infection with a low incidence. Sub-clinical and
      anicteric infections may occur. Elevation of gamma glutamyltranspeptidase is an
      important parameter of the biochemical profile of the disease.

PMID- 19841499
TI  - Reversal of hepatorenal syndrome in cirrhotic patients with terlipressin plus
      albumin. First experience in Mexico.
AB  - INTRODUCTION: Type 1 hepatorenal syndrome (HRS) is a functional renal failure
      that complicates end-stage cirrhosis. The vasopressin analogue terlipressin has
      been associated with improved renal function in patients with type 1 HRS. AIM: To
      evaluate the effectiveness of an infusion of terlipressin plus albumin in
      reversing type 1 HRS, its tolerability, and its adverse effects. METHODS:
      Thirteen consecutive patients with cirrhosis and type 1 HRS were included in the
      study. All patients received terlipressin plus albumin as treatment for HRS. The
      patients were divided in two groups. Group 1 contained eight patients in whom HRS
      was reversed with treatment, who were classified as responders. Group 2 contained
      five patients who were nonresponders. RESULTS: Sixty-one percent of the patients
      who received terlipressin plus albumin responded to therapy and underwent HRS
      reversal. In two patients, treatment with terlipressin was stopped because of
      adverse events. No relapse of HRS after terlipressin withdrawal was observed in
      this study. CONCLUSION: The rate of successful treatment with terlipressin plus
      albumin was 61%, similar to that in previously reported controlled trials.
      However, this is the first experience reported in Mexico. A cardiovascular
      evaluation is required before the start of treatment with terlipressin. This
      treatment appears to be an effective therapy for improving renal function in
      patients with type 1 HRS.

PMID- 19841500
TI  - Hepatocellular carcinoma: epidemiological profile from a cohort of federal
      employees in Mexico.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) has become a frequent type of cancer
      in Mexico. At the present time it represents the 19th cause of death in the
      population. OBJECTIVE: To recognize the epidemiological profile and the treatment
      results in a cohort of federal employees with HCC. MATERIAL AND METHODS: We
      analyzed 47 consecutive cases with HCC diagnosis from January 2004 till December
      2007. Twenty four demographic data, tumor staging, clinical, and biochemical
      variables were analyzed to identify parameters predicting survival by computing
      Kaplan-Mier and Mantel-Cox survival curves. RESULTS: Patient reference increased
      5% each year. The mean age was 60.4 years, 63.8% female sex, and 72.3% had
      cirrhosis, 44.7% had Hepatitis C infection. Most patients presented with advanced
      disease: 55.3% were AJCC stage 3 and 21.3% stage 4, 51.1% were BCLC class D. Mean
      tumor size was 8.09 cm. Median survival time from diagnosis was 122 days.
      Patients that did not receive treatment had a median survival of 70 days; the
      longest survival of patients was of those that received transarterial
      chemoembolization with a median of 707 days, followed by surgery with 683 days.
      Univariate analysis showed survival was associated to MELD score, AJCC and BCLC
      staging, creatinine level and ascites. Multivariate analysis showed tumor
      differentiation, AJCC staging and the choice of treatment to be related to the
      risk of death. CONCLUSION: An increase in the referral of HCC was demonstrated.
      Most patients had cirrhosis and HCV infection. Due to advance disease staging,
      TACE was the treatment that offered longest survival.

PMID- 19841501
TI  - Percutaneous ethanol injection before liver transplantation in the hepatocellular
      carcinoma.
AB  - BACKGROUND/OBJECTIVES: The study evaluates the outcome of patients who performed
      orthotopic liver transplantation (LT) as treatment for hepatocellular carcinoma
      (HCC), with percutaneous ethanol injection (PEI) while on the waiting list,
      verifying the effectiveness of this treatment in producing tumor necrosis and
      avoiding dropout and identifying treatment-related complications. MATERIAL AND
      METHODS: Medical records of 97 patients on the waiting list for LT at Hospital
      Clinic of Barcelona were examined. Sixty-two (56.3%) patients had been treated
      with PEI (group 1); 35 (31.8%) had not received any anti-tumor therapy before LT
      (group 2). RESULTS: Complete necrosis of the tumor was observed in 38/59 (64.3%)
      patients. The presence of additional nodules in the explant and the diameter of
      the main tumor of group 1 was significantly lower than in group 2 (p = 0.002).
      Dropout related to tumor progression occurred in 4.8% and 8.5%, and tumor
      recurrence in 5% and 6.2% for groups 1 and 2, respectively. Major complications
      were not evidenced after 421 PEI sessions and there was no tumor implant in the
      needle traject. CONCLUSIONS: In conclusion, the percutaneous treatment of HCC
      with PEI is a safe and effective method before the LT.

PMID- 19841502
TI  - Effects of Japanese herbal medicine Inchin-ko-to on endotoxin-induced cholestasis
      in the rat.
AB  - BACKGROUND/OBJECTIVE: Inchin-ko-to (ICKT) is an herbal medicine used in Japan to
      treat jaundice and liver fibrosis.We investigated the effect of oral ICKT
      supplementation on endotoxin-induced cholestasis in the rat. MATERIAL AND
      METHODS: Lipopolysaccharide (LPS) injection (1 mg/kg body weight i.p.) was used
      as a model of sepsis-induced cholestasis. Bile flow, biliary bile salt secretion,
      biliary glutathione secretion and protein expression of the main hepatobiliary
      transporters Na(+)-taurocholate-cotransporting peptide (Ntcp), multidrug
      resistance protein 2 (Mrp2) and bile salt export pump (Bsep) were analyzed by
      conventional techniques in ICKT treated and non-treated animals. RESULTS:
      Injection of LPS induced a significant decrease of bile flow (-24%), biliary bile
      salts (-40%) and glutathione excretion (-70%) as well as a significant decrease
      in Ntcp (-90%) and Mrp2 (-80%) protein levels. ICKT supplementation partially
      prevented the effects of LPS determining a less intense reduction in bile flow (
      10%), a normalization of glutathione excretion as well as a significant increase
      in Mrp2 protein levels to 60% of the levels observed in control animals. ICKT
      administration did not modify the effects of LPS on BS secretion or Ntcp protein
      levels. CONCLUSION: Our data show that oral supplementation of ICKT partially
      prevents LPS-induced cholestasis by increasing Mrp2 protein levels and biliary
      glutathione excretion thus increasing bile salt-independent flow.

PMID- 19841503
TI  - The effects of pegylated interferon alpha 2b on bile-duct ligation induced liver
      fibrosis in rats.
AB  - OBJECTIVE: To test the effects of peginterferon in an unrecoverable model of bile
      duct ligation (BDL) induced liver fibrosis. MATERIAL AND METHODS: Thirty-seven
      Wistar rats were divided into five groups: group 1, BDL + peginterferon (n = 8);
      group 2, BDL (n = 8); group 3, sham + peginterferon (n = 7); group 4, sham (n =
      7); and group 5, control group (n = 7). Peginterferon-alpha 2b (50 microgr/kg) or
      saline (1 mL/kg) was administered intraperitonealy every week for four weeks.
      Serum biochemical markers, liver tissue oxidative stress, collagen and
      transforming growth factor-beta (TGF-beta) levels were examined after four weeks.
      Liver slides were stained by hematoxylin and eosin and Masson trichrome?Gomory
      reticulum staining. RESULTS: The levels of tissue collagen, TGF-beta, biochemical
      markers (AST, ALT, bilirubins, alkaline phosphates, gamma-glutamyl
      transpeptidase) and oxidative stress markers (Malondialdehyde, luminal,
      lucigenin) of the BDL group were higher than the sham operated and control groups
      (all-p < 0.001). Peginterferon improved malondialdehyde, luminal and glutathione
      levels in the BDL + peginterferon group (p < 0.05). Histopathological examination
      of the BDL groups showed stage-3 fibrosis, while all the control groups were
      normal. Peginterferon showed no improvement in fibrosis either histologically, or
      biochemically. CONCLUSIONS: Peginterferon improved levels of malondialdehyde,
      glutathione and luminal in the rat model of BDL induced liver fibrosis.
      Peginterferon however,showed no anti-fibrotic effects in this model and therefore
      may not be a useful treatment for liver fibrosis.

PMID- 19841504
TI  - Mycobacterium avium complex in the liver.

PMID- 19841505
TI  - Unusual case of plasmablastic non-Hodgkin's lymphoma located in the liver. First
      case reported in an AIDS patient.
AB  - Plasmablastic lymphoma is a rare and a relatively new entity that was first
      described in the jaws and the oral cavity of HIV-AIDS patients. We report a case
      of plasmablastic lymphoma involving the liver in an AIDS patient. Plasmablastic
      lymphoma is considered a diffuse large B-cell lymphoma with a unique phenotype
      and predilection for the oral cavity. The case presented had a unique hepatic
      lesion, localized in the left lobe of the liver. Diagnosis was confirmed by
      hepatic biopsy guided by Computerized Tomography scan and histopathology. The
      smears showed a dense infiltrate composed by atypical lymphocytes with numerous
      plasmocytes expressing the plasma cell markers MUM-1 and CD138 and negative for
      the B-cell markers CD3, CD20 and CD45. Immunohistochemical and in situ
      hybridization revealed the Epstein-Barr virus genome in the atypical cells.
      Polymerase chain reaction was negative for HHV-8 RNA.

PMID- 19841506
TI  - Gilbert's syndrome and antiviral therapy of hepatitis C.
AB  - Treatment of chronic hepatitis C with type I interferons and ribavirin can be
      associated with exacerbation of hepatitis and sometimes liver decompensation. We
      report two patients with chronic hepatitis C virus infection who experienced a
      severe increase of bilirubin levels of up to 17 times upper the limit of normal
      value in the absence of deterioration of hepatic function during therapy with
      pegylated-interferon and ribavirin. A genetic disposition for Gilbert's syndrome
      explained the adverse events and permitted a continuation of therapy leading to a
      sustained clearance of chronic hepatitis C infection. Since one patient jaundiced
      already during a lead-in treatment period with ribavirin monotherapy we suggest
      that hyperbilirubinaemia during combination therapy is primarily caused by
      ribavirin rather than by effects of interferon alpha on UDP
      glucuronosyltransferase activities. Of note, both patients recovered from their
      initial unconjugated hyperbilirubinemia despite continuation of ribavirin
      therapy, which indicates that compensatory mechanisms leading to a normalization
      of UGT1A1 activity are likely.

PMID- 19841507
TI  - Mexican-native human echinococcosis: case report of an underestimated disease.
AB  - Mexico is considered a virtually free region of cystic echinococcosis. Almost all
      case reports within the country involve immigrants or traveling patients. This
      manuscript presents a Mexican-native human echinococcosis that developed in the
      setting described below. Review of current evidence suggests that this infection
      has been underestimated.

PMID- 19841509
TI  - Severe hepatotoxicity by Indian Ayurvedic herbal products: a structured causality
      assessment.
AB  - The case of a 64 year old female patient is presented who has treated herself for
      9 months with various Indian Ayurvedic herbal products for her vitiligo and
      experienced a causally related severe hepatotoxicity (ALT, 601 U/L; AST, 663 U/L;
      Bilirubin, 5.0 mg/dL). After discontinuation, a rapid improvement was observed.
      Causality assessment with the updated CIOMS (Council for International
      Organizations of Medical Sciences) scale showed a probable causality (+8 points)
      for Bakuchi tablets containing extracts from Psoralea corylifolia leaves with
      psoralens as ingredients, as the primary candidate causing the hepatotoxic
      reaction. The degree of probability was lower with +6 points for other used
      herbs: Khadin tablets containing extracts from Acacia catechu leaves; Brahmi
      tablets containing Eclipta alba or Bacopa monnieri; and Usheer tea prepared from
      Vetivexia zizaniodis. The case is the first report of Indian Ayurvedic herbal
      products being potentially hepatotoxic in analogy to some other herbs.

PMID- 19841508
TI  - Multiple pyogenic liver abscesses caused by Streptococcus constellatus in the
      Amazon region. Case report.
AB  - There are few studies reporting pyogenic liver abscess (PLA) caused by
      Streptococcus constellatus in the medical literature. S. constellatus is a
      comensal microorganism that belongs to the Streptococcus milleri's bacteria group
      and is not considered to be pathogenic for humans. We report the case of a 23
      year-old man with a 15-days history of abdominal pain in the right flank followed
      by daily fever, chills, nausea, vomits, sialism and jaundice. Physical
      examination revealed moderate jaundice (2+/4+), abdominal distention, generalized
      pain and tender over the right flank with positive Blumberg's sign. Additionally,
      the liver was palpable 5 cm below the costal margin in the right midclavicular
      line. Abdominal Computerized Tomography showed multiple hypodense hepatic images
      suggestive of liver abscesses. The patient underwent surgical exploration of the
      abdomen through a sub-costal incision and, during operation ruptured abscess
      localized on the hepatic segment III was drained. Culture of the purulent
      material obtained at surgery yielded Streptococcus constellatus as the causative
      agent. Liver abscess is a potential life-threatening disease that must be treated
      as soon as possible with invasive approaches, if necessary, and bacteriological
      studies performed when possible, allowing isolation of causative agents and
      specific antibiotic therapy.

PMID- 19841510
TI  - Emphasizing the importance of the clinical classification for pulmonary
      hypertension.

PMID- 19841511
TI  - Identification of genotype B among hepatitis B virus-infected patients in
      Hyderabad, India.

PMID- 19841513
TI  - Physical activity and nonalcoholic fatty liver disease.

PMID- 19841512
TI  - Venlafaxine-induced hepatotoxicity in a patient with ulcerative colitis.

PMID- 19841516
TI  - A generalized inverse planning tool for volumetric-modulated arc therapy.
AB  - The recent development in linear accelerator control systems, named volumetric
      modulated arc therapy (VMAT), has generated significant interest in arc-based
      intensity-modulated radiation therapy (IMRT). The VMAT delivery technique
      features simultaneous changes in dose rate, gantry angle and gantry rotation
      speed as well as multi-leaf collimator (MLC) leaf positions while radiation is
      on. In this paper, we describe a generalized VMAT planning tool that is designed
      to take full advantage of the capabilities of the new linac control systems. The
      algorithm incorporates all of the MLC delivery constraints such as restrictions
      on MLC leaf interdigitation and the MLC leaf velocity constraints. A key feature
      of the algorithm is that it is able to plan for both single- and multiple-arc
      deliveries. Compared to conventional step-and-shoot IMRT plans, our VMAT plans
      created using this tool can achieve similar or better plan quality with less MU
      and better delivery efficiency. The accuracy of the obtained VMAT plans is also
      demonstrated through plan verifications performed on an Elekta Synergy linear
      accelerator equipped with a conventional MLC of 1 cm leaf width using a
      PreciseBeam VMAT linac control system.

PMID- 19841514
TI  - Reduction in x-ray scatter and radiation dose for volume-of-interest (VOI) cone
      beam breast CT--a phantom study.
AB  - With volume-of-interest (VOI) cone-beam computed tomography (CBCT) imaging, one
      set of projection images are acquired with the VOI collimator at a regular or
      high exposure level and the second set of projection images are acquired without
      the collimator at a reduced exposure level. The high exposure VOI scan data
      inside the VOI and the low exposure full-field scan data outside the VOI are then
      combined together to generate composite projection images for image
      reconstruction. To investigate and quantify scatter reduction, dose saving and
      image quality improvement in VOI CBCT imaging, a flat panel detector-based bench
      top experimental CBCT system was built to measure the dose, the scatter-to
      primary ratio (SPR), the image contrast, noise level, the contrast-to-noise ratio
      (CNR) and the figure of merit (FOM) in the CBCT reconstructed images for two
      polycarbonate cylinders simulating the small and the large phantoms. The results
      showed that, compared to the full field CBCT technique, radiation doses for the
      VOI CBCT technique were reduced by a factor of 1.20 and 1.36 for the small and
      the large phantoms at the phantom center, respectively, and from 2.7 to 3.0 on
      the edge of the phantom, respectively. Inside the VOI, the SPRs were
      substantially reduced by a factor of 6.6 and 10.3 for the small and the large
      phantoms, the contrast signals were improved by a factor of 1.35 and 1.8, and the
      noise levels were increased by a factor of 1.27 and 1.6, respectively. As a
      result, the CNRs were improved by a factor of 1.06 and 1.13 for the small and the
      large phantoms and the FOM improved by a factor of 1.4 and 1.7, respectively.

PMID- 19841515
TI  - Dynamic contrast-enhanced diffuse optical tomography (DCE-DOT): experimental
      validation with a dynamic phantom.
AB  - Dynamic contrast-enhanced diffuse optical tomography (DCE-DOT) can provide
      spatially resolved enhancement kinetics of an optical contrast agent. We
      undertook a systematic phantom study to evaluate the effects of the geometrical
      parameters such as the depth and size of the inclusion as well as the optical
      parameters of the background on the recovered enhancement kinetics of the most
      commonly used optical contrast agent, indocyanine green (ICG). For this purpose a
      computer-controlled dynamic phantom was constructed. An ICG-intralipid-water
      mixture was circulated through the inclusions while the DCE-DOT measurements were
      acquired with a temporal resolution of 16 s. The same dynamic study was repeated
      using inclusions of different sizes located at different depths. In addition to
      this, the effect of non-scattering regions was investigated by placing a second
      inclusion filled with water in the background. The phantom studies confirmed that
      although the peak enhancement varied substantially for each case, the recovered
      injection and dilution rates obtained from the percentage enhancement maps agreed
      within 15% independent of not only the depth and the size of the inclusion but
      also the presence of a non-scattering region in the background. Although no
      internal structural information was used in these phantom studies, it may be
      necessary to use it for small objects buried deep in tissue. However, the
      different contrast mechanisms of optical and other imaging modalities as well as
      imperfect co-registration between both modalities may lead to potential errors in
      the structural a priori. Therefore, the effect of erroneous selection of
      structural priors was investigated as the final step. Again, the injection and
      dilution rates obtained from the percentage enhancement maps were also immune to
      the systematic errors introduced by erroneous selection of the structural priors,
      e.g. choosing the diameter of the inclusion 20% smaller increased the peak
      enhancement 60% but changed the injection and dilution rates only less than 10%.

PMID- 19841517
TI  - Synchrotron microbeam radiation therapy for rat brain tumor palliation-influence
      of the microbeam width at constant valley dose.
AB  - To analyze the effects of the microbeam width (25, 50 and 75 microm) on the
      survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues
      in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted
      in rat brains, as well as in normal rat brains, were irradiated in the MRT mode.
      Three configurations (MRT25, MRT50, MRT75), each using two orthogonally
      intersecting arrays of either 25, 50 or 75 microm wide microbeams, all spaced 211
      microm on center, were tested. For each configuration, peak entrance doses of
      860, 480 and 320 Gy, respectively, were calculated to produce an identical valley
      dose of 18 Gy per individual array at the center of the tumor. Two, 7 and 14 days
      after radiation treatment, 42 rats were killed to evaluate histopathologically
      the extent of tumor necrosis, and the presence of proliferating tumors cells and
      tumor vessels. The median survival times of the normal rats were 4.5, 68 and 48
      days for MRT25, 50 and 75, respectively. The combination of the highest entrance
      doses (860 Gy per array) with 25 microm wide beams (MRT25) resulted in a
      cumulative valley dose of 36 Gy and was excessively toxic, as it led to early
      death of all normal rats and of approximately 50% of tumor-bearing rats. The
      short survival times, particularly of rats in the MRT25 group, restricted
      adequate observance of the therapeutic effect of the method on tumor-bearing
      rats. However, microbeams of 50 microm width led to the best median survival time
      after 9L gliosarcoma MRT treatment and appeared as the better compromise between
      tumor control and normal brain toxicity compared with 75 microm or 25 microm
      widths when used with a 211 microm on-center distance. Despite very high
      radiation doses, the tumors were not sterilized; viable proliferating tumor cells
      remained present at the tumor margin. This study shows that microbeam width and
      peak entrance doses strongly influence tumor responses and normal brain toxicity,
      even if valley doses are kept constant in all groups. The use of 50 microm wide
      microbeams combined with moderate peak doses resulted in a higher therapeutic
      ratio.

PMID- 19841518
TI  - Organ dose conversion coefficients on an ICRP-based Chinese adult male voxel
      model from idealized external photons exposures.
AB  - A high-resolution whole-body voxel model called CAM representing the Chinese
      adult male was constructed in this paper based on a previous individual voxel
      model. There are more than 80 tissues and organs in CAM, including almost all
      organs required in the ICRP new recommendation. The mass of individual organs has
      been adjusted to the Chinese reference data. Special considerations were given to
      representing the gross spatial distribution of various bone constituents as
      realistically as possible during the construction of the site-specific skeleton.
      Organ dose conversion coefficients were calculated for six idealized external
      photon exposures from 10 keV to 10 MeV by using Monte Carlo simulation. The
      resulting dose coefficients were then compared with those from other models, e.g.
      CMP, ICRP 74, Rex, HDRK-man and VIP-man. Old and new effective male doses of CAM
      were calculated by using the tissue weighting factors from ICRP 60 and 103
      Publications, respectively. Dosimetric differences between mathematical and voxel
      models, and the differences between Asian and Caucasian models are also discussed
      in this paper.

PMID- 19841519
TI  - An ICRP-based Chinese adult male voxel model and its absorbed dose for idealized
      photon exposures--the skeleton.
AB  - A site-specific skeleton voxel model for a Chinese adult male was constructed in
      this paper upon a previous Chinese individual voxel model. The whole skeleton was
      divided into 19 site-specific bones and bone groups; the mass of various skeleton
      tissues at each bone site, e.g. red bone marrow, was specified according to Asian
      reference data and the distribution data from ICRP Publication 70. The resultant
      voxel model (called CAM) has a resolution of 1.741 mm x 1.741 mm in plane, and
      the total bone mass is 8397.8 g which is almost equal to the Asian reference
      value. Dose coefficients for the red bone marrow and bone surface in CAM were
      calculated, and then compared with those from Rex, CMP and ICRP 74. It shows that
      the dose to RBM in Rex is generally 12% lower than that to CAM in low-energy
      range (30-150 keV) for AP, LAT, ROT and ISO geometries. It is also found that the
      RBM dose from mathematical models, i.e. CMP and ICRP 74, is underestimated by 
      30% in AP geometry and overestimated by 30% in PA geometry for low-energy
      photons. Meanwhile, the bone surface dose in the low-energy range is
      overestimated by 150% and 75% in CMP and ICRP 74, respectively, if compared with
      that from CAM.

PMID- 19841520
TI  - Ethical issues and living unrelated donor kidney transplantation.
AB  - During the past decades, the number of altruistic living unrelated kidney
      donations has substantially increased in developed countries. However, the
      altruistic supply of transplantable kidneys has remained much less than the
      demand. As a result, severe kidney shortage has been associated with increasing
      number of patient deaths and increasing number of commercial transplants and
      transplant tourism. Studies have shown that there is still a need for living
      kidney donation because even all potential brain-dead donors cannot supply the
      escalating need for kidneys. The use of living unrelated kidney donors should be
      morally and ethically justified and should be compatible with ethical principles.
      Many experts believe that increasing number of patient deaths and commercial
      transplants will continue to happen if kidney donation system remains merely
      altruistic. While some transplant professionals support a paid and regulated
      system to eliminate kidney shortage, others argue that it will be destructive.
      Iran has a 20-year experience with a compensated and regulated living unrelated
      kidney donation program. This transplantation model was adopted in 1988, and
      successfully eliminated kidney transplant waiting list by the end of 1999.
      Currently, more than 50% of patients with end-stage kidney disease in Iran are
      living with a functioning graft. This Iranian transplantation model has many
      ethical successes. However, because it has not been well regulated by transplant
      ethicists, some ethical shortcomings have remained. Unfortunately, due to lack of
      interest and expertise in health authorities, the number of serious ethical
      failures is also increasing in this transplantation model.

PMID- 19841521
TI  - Changing epidemiology of end-stage renal disease in last 10 years in Iran.
AB  - INTRODUCTION: The rapid increase in the prevalence of end-stage renal disease
      (ESRD) necessitates putting into practice some strategies to prevent its
      development and progression, especially in the developing world. Detailed
      chronological changes in the incidence of ESRD may sharpen the focus on its
      prevention. We, therefore, determined the detailed epidemiological features of
      ESRD in Iran. MATERIALS AND METHODS: Data of the national registry of Iran's ESRD
      provided by the Ministry of Health were used to retrieve the ESRD figures between
      1997 and 2006. RESULTS: A total of 35 859 patients who initiated renal
      replacement therapy (20 633 men and 15 226 women) were registered during the
      study period from 1997 to 2006. The annual number of patients with ESRD beginning
      maintenance treatment in Iran increased 130% between 2000 and 2006. During 1997
      to 2006, the proportion of new cases of ESRD attributed to diabetes mellitus
      increased 2-fold from 16% in 1997 to 31% in 2006. The mean age of newly
      registered men and women increased from 47.0 years and 49.0 years to 52.5 years
      and 53.0 years, respectively. As for all and major causes of ESRD, age-adjusted
      incidence rates for men generally were higher than those for women. Male-female
      ratio was 1.3:1, with no significant changes during this period. CONCLUSIONS: We
      strongly recommend considering chronic kidney disease prevention with initial
      focusing on strategies and treatment modalities that slow ESRD progression in
      order to postpone the need for renal replacement therapy.

PMID- 19841522
TI  - Reduction of kidney damage by supplementation of vitamins C and E in rats with
      deoxycorticosterone-salt-induced hypertension.
AB  - INTRODUCTION: We assessed whether co-supplementation of vitamins C and E has
      additive beneficial effects on reducing the kidney damage and attenuation of the
      arterial pressure elevation compared to administration of either vitamin C or
      vitamin E alone in deoxycorticosterone acetate-salt-induced hypertension.
      MATERIALS AND METHODS: Forty rats were divided into 4 study groups and 1 sham
      operated group. Unilateral nephrectomy was carried out in the study groups and
      hypertension was induced by deoxycorticosterone injection and 1% sodium chloride
      and 0.2% potassium chloride added to the drinking water. Vitamins C and E (200
      mg/kg/day) or combination of them were administered with DOCA-salt for 4 weeks in
      3 study groups. The effects of DOCA and salt and treatment with vitamins were
      compared in terms of blood pressure, urinary protein excretion, antioxidant
      activity of the kidneys, and renal histological changes. RESULTS: Four weeks of
      supplementations of vitamins C, vitamin E, and both in the DOCA-salt-treated rats
      had comparable significant effects in decreasing systolic blood pressure. Urinary
      protein excretion and histological damage did not significantly change with the
      combination therapy of vitamins C and E compared to the vitamin C or E alone. The
      renal levels of glutathione and ferric reducing/antioxidant power in combination
      therapy group were similar to the two other treatment groups and were
      significantly higher than non-treated group. CONCLUSIONS: Co-administration of
      vitamin C and E does not have an additive beneficial effect on reducing the
      kidney damage and hypertension compared to either vitamin C or E alone in DOCA
      salt-induced hypertension.

PMID- 19841523
TI  - Arterial atherosclerosis in patients with chronic kidney disease and its
      relationship with serum and tissue endothelin-1. [corrected].
AB  - Instruction. We investigated the correlation between atherosclerosis and tissue
      and serum levels of endothelin-1 in patients with chronic kidney disease (CKD).
      MATERIALS AND METHODS. Arterial samples were obtained from 35 patients with CKD
      during arteriovenous fistula placement. Thirty-one patients with cardiovascular
      disease who underwent coronary artery bypass graft (CABG) were selected as the
      atherosclerotic group, and a piece of their aorta punched during CABG was
      obtained. Also, a small piece of the renal artery was dissected during donation
      in 24 kidney donors (control group). Tissue endothelin-1 level was measured and
      atherosclerosis grading was determined by pathologic examination. Serum levels of
      endothelin-1 were also measured in the three groups. Results. The mean tissue
      endothelin-1 levels were 10.73+/-7.57 pg/mL, 12.16 +/- 3.95 pg/mL, and 0.93 +/-
      1.06 pg/mL in the patients with CKD, those with CABG, and donors, respectively (P
      < .001). The mean serum endothelin-1 level was 25.23 +/- 15.15 pg/mL in the
      patients with CKD, 21.13 +/- 17.22 pg/mL in the patients with CABG, and 2.66 +/-
      1.51 pg/mL in the donors (P < .001). Atherosclerosis grades correlated with
      tissue endothelin-1 level (r = 0.823, P < .001) and serum endothelin-1 level (r =
      0.608, P < .001) in the patients with CKD. Multiple regression analysis showed
      tissue endothelin-1 level as the main predicting factor of atherosclerosis (P <
      .001). CONCLUSIONS. Tissue endothelin-1 concentration is more important than
      serum endothelin-1 or lipids levels in prediction of atherosclerosis. Thus,
      blockade of tissue endothelin-1 receptors with its antagonists may prevent
      atherosclerosis progression.

PMID- 19841524
TI  - Management and outcome of steroid-resistant nephrotic syndrome in children.
AB  - INTRODUCTION: Steroid-resistant nephrotic syndrome (SRNS) is uncommon in
      children, but often leads to ESRD. We report our experience with SRNS and its
      treatments and outcomes. MATERIALS AND METHODS: We assessed 73 children with SRNS
      admitted to Ali Asghar Children Hospital in Tehran, Iran. Their clinical
      presentations, treatment, and disease courses were reviewed. The mean follow-up
      duration was 6.0 +/- 4.2 years. Moreover, survival times were calculated and the
      Cox regression method was used to determine variables able to predict survival of
      the kidneys. RESULTS: Age at the onset of the disease, sex, and hematuria were
      not predictive of the response to treatment with immunosuppressive drugs in the
      children with SRNS. The type of resistance (early or late) was associated with
      the responsiveness to immunosuppressives. Response to any of the
      immunosuppressive drugs determined the responsiveness to other immunosuppressive
      drugs. Cyclosporine was more effective than cyclophosphamide as initial therapy.
      The mean kidney survival time was 11.62 years. Kidney survival rates were 94.6%,
      70.0%, 56.0%, and 34.0% at 1, 5, 10, and 15 years, respectively, in patients with
      initial resistance to steroid, while these were 100%, 100%, 83.0%, and 83.0% in
      those with late resistance, respectively (P = .03). CONCLUSIONS: We showed that
      patients with late steroid resistance had better response to immunosuppressive
      drugs than patients with early resistance. We also showed that resistance to
      immunosuppressive therapies increased the risk of resistance to other
      immunosuppressive drugs. Achievement of complete or partial remission with any
      therapy reduced the risk of ESRD.

PMID- 19841525
TI  - Gastrointestinal manifestations of nephropathic cystinosis in children.
AB  - INTRODUCTION: Cystinosis is an autosomal recessive disorder which is
      characterized by both renal and extrarenal symptoms. Gastrointestinal dysfunction
      has been reported in adolescent with cystinosis, and it is rarely considered in
      the infants. The present case series reviewed gastrointestinal manifestations of
      these patients. MATERIALS AND METHODS: Gastrointestinal signs and symptoms of 23
      children aged 5.99 +/- 0.50 years (range, 1.0 to 12.5 years) on average with
      cystinosis, admitted to our department of nephrology between 1996 and 2005, were
      retrospectively reviewed. The inclusion criteria were the presence of the
      crystals of cystine in bone marrow aspiration and corneal deposition detected by
      slit lamp examination. RESULTS: Gastrointestinal signs and symptoms were as
      follows: vomiting in 16 patients (69.6%), hepatomegaly in 8 (34.8%), diarrhea in
      6 (26.1%), splenomegaly in 5 (21.7%), constipation in 4 (17.4%), anorexia in 4
      (17.4%), abdominal pain in 3 (13.0%), nausea in 2 (8.7%), and ascites in 2
      (8.7%). Height below the 3rd percentile in was seen in 16 patients (69.6%) and
      weight below the 3rd percentile, in 17 (73.9%). Fifteen patients (65.2%) had both
      low weight and low height. Esophagogastroduodenoscopy had been performed in 6
      cases and chronic inactive gastritis with H pylori infection was detected in 2
      patients (8.7%). CONCLUSIONS: Our study revealed a wide spectrum of
      gastrointestinal disturbances in young patients with cystinosis. Such findings
      should lead to greater awareness of the presence of gastrointestinal dysfunction
      in these children, encourage prompt gastrointestinal evaluation, and encourage
      treatment of more severely affected patients.

PMID- 19841526
TI  - Theophylline for prevention of kidney dysfunction in neonates with severe
      asphyxia.
AB  - INTRODUCTION: Recent studies have suggested theophylline for prevention of kidney
      dysfunction in asphyxia. This study was designed to determine whether
      theophylline could prevent or ameliorate kidney dysfunction in term neonates with
      perinatal asphyxia. MATERIALS AND METHODS: We assigned 36 severely asphyxiated
      term infants (Apgar score < or =5) into 2 groups to receive intravenously a
      single dose of either theophylline (5mg/kg; n =17) or placebo (n =19) during
      their first 60 minutes of life. The 24-hour fluid intake and the urine volumes
      were recorded during the 1st, 3rd, and 5th days of life. Severe kidney
      dysfunction was defined as a serum creatinine level elevated up to more than 1.50
      mg/dL for at least 2 consecutive days after a fluid challenge, or 0.3-mg/dL/d
      rising levels of serum creatinine. RESULTS: On the 1st day, the 24-hour fluid
      balance was more positive in infants receiving placebo compared to infants
      receiving theophylline. Over the next few days, the change in fluid balance
      favored the theophylline group. Significantly higher serum creatinine values were
      recorded in the placebo group on the 3rd day. Severe kidney dysfunction was
      present in 2 infants of the theophylline group (11.7. %) and in 8 (42.1%) of the
      controls. The glomerular filtration rate was markedly increased in the
      theophylline group. There was no difference in the severity of the asphyxia
      between the infants of the theophylline and control groups. CONCLUSIONS:
      Prophylactic theophylline, given early after birth, has beneficial effects on
      reducing kidney dysfunction in neonates with asphyxia.

PMID- 19841527
TI  - Different doses of oral folic acid for homocysteine-lowering therapy in patients
      on hemodialysis: a randomized controlled trial.
AB  - INTRODUCTION: We compared the effect of higher and lower doses of folic acid
      compared to our routine daily dose on plasma homocysteine levels, in our
      hemodialysis patients. MATERIALS AND METHODS: Eighty patients on hemodialysis
      receiving oral folic acid, 10 mg/d, were randomized to receive folic acid at
      either doses of 5 mg/d (group 1) or 15 mg/d (group 2) for 2 months. Plasma levels
      of total homocysteine were measured before and after the study period. RESULTS:
      Hyperhomocysteinemia was seen in 75 patients (93.8%) before, and in 37 patients
      of group 1 (92.5%) and 39 of group 2 (97.5%) after the study period. In group 1,
      a nonsignificant decrease occurred in plasma homocysteine level (29.67 +/- 12.26
      micromol/L to 27.78 +/- 9.94 micromol/L, P = .30), while in group 2, there was a
      significant decrease in homocysteine level (32.40 +/- 9.76 micromol/L to 29.58 +/
      9.62 micromol/L, P = .01). Changes in homocysteine level correlated with its
      baseline level (r = -0.42, P < .001). In both groups, significant reductions in
      homocysteine level were seen mostly in those patients with high baseline
      homocysteines. CONCLUSIONS: Routine folic acid supplementation of 10 mg/d could
      not normalize plasma homocysteine levels in most of our patients. Increasing
      folic acid dose made a statistically significant but clinically trivial decrease
      in homocysteine levels, and could not normalize homocysteine level in most
      patients. Patients with a higher baseline homocysteine level achieved a greater
      reduction, which may be explained by primary noncompliance of some patient.
      Further investigation of folic acid dosage is suggested.

PMID- 19841528
TI  - Estimation of glomerular filtration rate with creatinine-based versus cystatin C
      based equations in kidney transplant recipients.
AB  - INTRODUCTION: Serum cystatin C is more sensitive for glomerular filtration rate
      (GFR) measurement, but it is not available for clinical use in all laboratories.
      Regarding the importance of accurate estimation of GFR in kidney transplant
      recipients, we compared cystatin C-based equations with creatinine-based formulas
      to estimate GFR as precisely and simply as possible in kidney transplant
      recipients. MATERIALS AND METHODS: Seventy living donor kidney transplant
      recipients with stable kidney function were enrolled in our study. The patients'
      GFRs were estimated by 3 creatinine-based equations (the modification of diet in
      renal disease [MDRD], abbreviated MDRD, and Cockcroft-Gault) and 5 cystatin C
      based equations (Filler, Le Bricon, Rule, Hoek, and Larsson), and the results
      were analyzed. RESULTS: The mean age of the recipients was 38.7 +/- 13.4 years.
      The mean GFRs were 67.1 +/- 25.9 mL/min/1.73 m2, by the Cockcroft-Gault; 61.0 +/-
      17.7 mL/min/1.73 m2, by the abbreviated MDRD; and 60.0 +/-18.6 mL/min/1.73 m2, by
      the MDRD formulas. Cystatin C-based GFR estimations were 43.6 +/- 16.2
      mL/min/1.73 m2, 44.0 +/- 13.2 mL/min/1.73 m2, 33.8 +/- 14.1 mL/min/1.73 m2, 35.6
      +/- 13.7 mL/min/1.73 m2, and 36.9 +/- 13.6 mL/min/1.73 m2 by the Filler, Le
      Bricon, Larsson, Rule, and Hoek equations, respectively. The estimates by
      creatinine-based and cystatin C-based equations were significantly different and
      the MDRD estimate was the closest to the cystatin C-based GFRs. CONCLUSIONS: Our
      findings revealed the MDRD equation could be provide a closer estimate of GFR to
      the cystatin C-based equations than other creatinine-based GFR calculations in
      kidney transplant recipients.

PMID- 19841529
TI  - Incidence of end-stage renal disease in Guilan Province, Iran, 2005 to 2007.
AB  - We reviewed records of patients with ESRD in all dialysis and kidney transplant
      centers of Guilan province to determine the incidence and modalities for
      treatment of ESRD from 2005 to 2007. Records of 759 patients were reviewed during
      the 3-year period of the study. The male-female ratio was 1.34:1 and the men age
      at the time of diagnosis was 56.3 +/- 16.8 years. The most frequent age group was
      60 years and older (45.8%). The incidence ESRD during 2005, 2006, and 2007 were
      100.36 pmp, 100.60 pmp, and 110.66 pmp, respectively. The most common causes of
      ESRD were hypertension (29.4%), unknown (26.6%), and diabetes mellitus (17.9%).
      The most common modality at initiation of renal replacement therapy was
      hemodialysis (96.0%). The entrance rate of hemodialysis in 2005, 2006, and 2007
      were 29.6%, 35.0%, and 35.4%, and the discontinuing rate of hemodialysis in these
      years were 29.5%, 32.1%, and 38.4%, respectively.

PMID- 19841530
TI  - Revised dyadic adjustment scale as a reliable tool for assessment of quality of
      marital relationship in patients on long-term hemodialysis.
AB  - Although the revised dyadic adjustment scale (RDAS) has been widely used as an
      indicator of the quality of marital relationship, no report is available on the
      reliability of this measure in patients on hemodialysis. We examined the internal
      consistency of the RDAS in a group of Iranian patients undergoing maintenance
      hemodialysis. A translated Persian version of the RDAS was self-administered to
      135 patients. The internal consistency of the RDAS was tested using the Chronbach
      alpha coefficient which was 0.898, 0.683, 0.779, 0.827, and 0.836 for the RDAS
      total score and the dyadic consensus, affective expression, dyadic satisfaction,
      and dyadic cohesion subdomains, respectively. All of the Chronbach alpha scores
      were higher in patients with higher income and education level. Using the RDAS to
      examine marital relationship quality in patients on hemodialysis, the total score
      and almost all subscores except for dyadic consensus had adequate internal
      consistency.

PMID- 19841531
TI  - Cystic changes of breast in a family with autosomal dominant polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease is associated with cysts in many
      organs including the liver, pancreas, lungs, spleen, ovaries, testes, thyroid,
      and uterus. However, there is no report, to our knowledge, of cystic changes of
      the breast along with this disease. We describe 3 members of a family with
      multiple bilateral breast cysts in association with autosomal dominant polycystic
      kidney disease.

PMID- 19841532
TI  - Nephroquiz 3: nephrotic syndrome in adult patients with skin lesions.

PMID- 19841533
TI  - Ultrasonography-guided intracystic injection of appropriate antibiotics: valuable
      for treatment of pyocyst in autosomal dominant polycystic kidney disease?

PMID- 19841534
TI  - Low rate of proteinuria in children after exposure to low-dose melamine: no
      predicted false positivity due to melamine.

PMID- 19841535
TI  - Reno-renal syndrome: cross-talk between kidneys.

PMID- 19841536
TI  - Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic
      instability and inflammation.
AB  - Smad4 is a central mediator of TGF-beta signaling, and its expression is
      downregulated or lost at the malignant stage in several cancer types. In this
      study, we found that Smad4 was frequently downregulated not only in human head
      and neck squamous cell carcinoma (HNSCC) malignant lesions, but also in grossly
      normal adjacent buccal mucosa. To gain insight into the importance of this
      observation, we generated mice in which Smad4 was deleted in head and neck
      epithelia (referred to herein as HN-Smad4-/- mice) and found that they developed
      spontaneous HNSCC. Interestingly, both normal head and neck tissue and HNSCC from
      HN-Smad4-/- mice exhibited increased genomic instability, which correlated with
      downregulated expression and function of genes encoding proteins in the Fanconi
      anemia/Brca (Fanc/Brca) DNA repair pathway linked to HNSCC susceptibility in
      humans. Consistent with this, further analysis revealed a correlation between
      downregulation of Smad4 protein and downregulation of the Brca1 and Rad51
      proteins in human HNSCC. In addition to the above changes in tumor epithelia,
      both normal head and neck tissue and HNSCC from HN-Smad4-/- mice exhibited severe
      inflammation, which was associated with increased expression of TGF-beta1 and
      activated Smad3. We present what we believe to be the first single gene-knockout
      model for HNSCC, in which both HNSCC formation and invasion occurred as a result
      of Smad4 deletion. Our results reveal an intriguing connection between Smad4 and
      the Fanc/Brca pathway and highlight the impact of epithelial Smad4 loss on
      inflammation.

PMID- 19841537
TI  - Homocysteine inhibits neoangiogenesis in mice through blockade of annexin A2
      dependent fibrinolysis.
AB  - When plasma levels of homocysteine (HC), a thiol amino acid formed upon
      methionine demethylation, exceed 12 muM, individuals are at increased risk of
      developing large vessel atherothrombosis and small vessel dysfunction. The
      annexin A2 complex (termed "A2") is the cell surface coreceptor for plasminogen
      and TPA and accelerates the catalytic activation of plasmin, the major
      fibrinolytic agent in mammals. We previously showed that HC prevents A2-mediated,
      TPA-dependent activation of plasminogen in vitro by disulfide derivatization of
      the "tail" domain of A2. We also demonstrated that fibrinolysis and angiogenesis
      are severely impaired in A2-deficient mice. We now report here that, although
      hyperhomocysteinemic mice had a normal coagulation profile and normal platelet
      function, fibrin accumulated in their tissues due to reduced perivascular
      fibrinolytic activity and angiogenesis was impaired. A2 isolated from
      hyperhomocysteinemic mice failed to fully support TPA-dependent plasmin
      activation. However, infusion of hyperhomocysteinemic mice with fresh recombinant
      A2, which localized to neoangiogenic endothelial cells, resulted in normalization
      of angiogenesis and disappearance of peri- and intravascular fibrin. We therefore
      conclude that hyperhomocysteinemia impairs postnatal angiogenesis by derivatizing
      A2, preventing perivascular fibrinolysis, and inhibiting directed endothelial
      cell migration. These findings provide a mechanistic explanation for
      microvascular dysfunction and macrovascular occlusion in individuals with
      hyperhomocysteinemia.

PMID- 19841538
TI  - The APCs of neuroprotection.
AB  - Mutations in the enzyme superoxide dismutase 1 (SOD1) have been linked to the
      neurodegenerative disease amyotrophic lateral sclerosis (ALS). In this issue of
      the JCI, Zhong et al. report that the endogenous anticoagulant activated protein
      C (APC) is able to cross the blood-spinal cord barrier in mice and signal to both
      neuronal and non-neuronal cells (see the related article beginning on page 3437).
      This signaling resulted in the suppression of mutant SOD1 synthesis and retarded
      disease progression in a murine model of ALS. Here we discuss the potential
      importance of these data and possible relevance to human neurodegenerative
      diseases.

PMID- 19841539
TI  - Homocysteine-mediated thrombosis and angiostasis in vascular pathobiology.
AB  - The mechanisms by which homocysteine contributes to atherothrombosis are complex
      and their in vivo relevance uncertain. In this issue of the JCI, Jacovina and
      colleagues report a unique in vivo mechanism by which homocysteine may contribute
      to vascular disease (see the related article beginning on page 3384). This group
      had previously reported that homocysteine impairs endothelial cell surface
      plasminogen activation by posttranslationally modifying annexin A2, the
      coreceptor for plasminogen and tissue plasminogen activator. They now show that
      an annexin A2-deficient mouse rendered hyperhomocysteinemic by dietary means has
      impaired fibrinolysis, perivascular fibrin persistence, and attenuated
      angiogenesis (angiostasis). Potential mechanisms by which homocysteine-dependent
      changes in endothelial phenotype link thrombosis to angiostasis are reviewed and
      their relationship to homocysteine-dependent vascular disease considered.

PMID- 19841540
TI  - Smad4: gatekeeper gene in head and neck squamous cell carcinoma.
AB  - Unchecked cell growth is a hallmark of cancer. During oncogenesis, cancerous
      cells become resistant to the TGF-beta signaling pathway that usually keeps cell
      growth in check. The role of a critical mediator of this pathway, Smad4, in head
      and neck squamous cell carcinoma (HNSCC) remains unclear. In this issue of the
      JCI, Bornstein and colleagues report that Smad4 expression is decreased in
      malignant HNSCC and, surprisingly, also in normal-appearing buccal mucosa
      adjacent to HNSCC (see the related article beginning on page 3408). They also
      show that targeted conditional deletion of Smad4 in the head and neck epithelium
      of mice is alone sufficient to initiate spontaneous HNSCC, in conjunction with
      DNA repair gene dysregulation, genetic instability, and inflammation. These
      findings point to a novel function for Smad4 as a guardian gene that maintains
      genomic stability.

PMID- 19841541
TI  - The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory
      channel in mouse kidney.
AB  - Renal outer medullary potassium (ROMK) channels are exquisitely regulated to
      adjust renal potassium excretion and maintain potassium balance. Clathrin
      dependent endocytosis plays a critical role, limiting urinary potassium loss in
      potassium deficiency. In renal disease, aberrant ROMK endocytosis may contribute
      to potassium retention and hyperkalemia. Previous work has indicated that ROMK
      endocytosis is stimulated by with-no-lysine (WNK) kinases, but the endocytotic
      signal and the internalization machinery have not been defined. Here, we found
      that ROMK bound directly to the clathrin adaptor molecule autosomal recessive
      hypercholesterolemia (ARH), and this interaction was mediated by what we believe
      to be a novel variant of the canonical "NPXY" endocytotic signal, YxNPxFV. ARH
      recruits ROMK to clathrin-coated pits for constitutive and WNK1-stimuated
      endocytosis, and ARH knockdown decreased basal rates of ROMK endocytosis, in a
      heterologous expression system, COS-7 cells. We found that ARH was predominantly
      expressed in the distal nephron where it coimmunoprecipitated and colocalized
      with ROMK. In mice, the abundance of kidney ARH protein was modulated by dietary
      potassium and inversely correlated with changes in ROMK. Furthermore, ARH
      knockout mice exhibited an altered ROMK response to potassium intake. These data
      suggest that ARH marks ROMK for clathrin-dependent endocytosis, in concert with
      the demands of potassium homeostasis.

PMID- 19841543
TI  - Natural prevalence of antibody titres to GTF of S. mutans in saliva in high and
      low caries active children.
AB  - The present study was conducted to find out the role of natural immunity against
      dental caries. Whole stimulated saliva of various caries from active children was
      collected. Antigen glucosyltransferase (GTF) was prepared from Streptococcus
      mutans serotype C and the antibody titre was estimated using ELISA. Salivary IgG,
      s-IgA and total immunoglobulins (IgG + s-IgA+ IgM) concentration were assayed.
      The result showed an increased level of salivary IgG concentration with the
      increased number of dental caries, which was not statistically significant. But
      there were significant decrease of s-IgA titre as well as total immunoglobulin
      concentration in saliva with the increased number of dental caries. This study
      showed that because of lack of local immunity the children are more prone to
      dental caries.

PMID- 19841542
TI  - Activated protein C therapy slows ALS-like disease in mice by transcriptionally
      inhibiting SOD1 in motor neurons and microglia cells.
AB  - Activated protein C (APC) is a signaling protease with anticoagulant activity.
      Here, we have used mice expressing a mutation in superoxide dismutase-1 (SOD1)
      that is linked to amyotrophic lateral sclerosis (ALS) to show that administration
      of APC or APC analogs with reduced anticoagulant activity after disease onset
      slows disease progression and extends survival. A proteolytically inactive form
      of APC with reduced anticoagulant activity provided no benefit. APC crossed the
      blood-spinal cord barrier in mice via endothelial protein C receptor. When
      administered after disease onset, APC eliminated leakage of hemoglobin-derived
      products across the blood-spinal cord barrier and delayed microglial activation.
      In microvessels, motor neurons, and microglial cells from SOD1-mutant mice and in
      cultured neuronal cells, APC transcriptionally downregulated SOD1. Inhibition of
      SOD1 synthesis in neuronal cells by APC required protease-activated receptor-1
      (PAR1) and PAR3, which inhibited nuclear transport of the Sp1 transcription
      factor. Diminished mutant SOD1 synthesis by selective gene excision within
      endothelial cells did not alter disease progression, which suggests that
      diminished mutant SOD1 synthesis in other cells, including motor neurons and
      microglia, caused the APC-mediated slowing of disease. The delayed disease
      progression in mice after APC administration suggests that this approach may be
      of benefit to patients with familial, and possibly sporadic, ALS.

PMID- 19841544
TI  - A comparative study to evaluate the effect of fluoride releasing sealant cured by
      visible light, argon lasers, and light emitting diode curing units: an in vitro
      study.
AB  - In Pediatric Dentistry, the use of pit and fissure sealant is one of the
      essential forms of prevention. Pit and fissure caries may be substantially
      decreased by obliteration of these developmental defects in occlusal, buccal and
      lingual surfaces with resin based dental sealants. Visible light-curing units, or
      LCUs, are an integral part of modern adhesive dentistry" They are used to cure
      resin based composite restoration materials, resin modified glass-ionomer and pit
      and fissure sealants, as well as to bond orthodontic teeth. Most recently, the
      argon laser has been approved for initiating the setting reaction with visible
      light cured-resins. Argon curing of resin materials has been show to enhance the
      physical properties and degree of polymerization of the resin, while reducing the
      polymerization time by 75 percent. The study is undertaken considering the
      inadequate research reports of regarding the comparison of curing ability using
      argon laser. LEDs and visible light as well as the resistant towards caries
      activity of the preventive fluoride releasing pit and fissure sealant cured by
      above mentioned curing units.

PMID- 19841545
TI  - Evaluation of children's behavior aged 0-3 years during dental care: a
      longitudinal analysis.
AB  - Child temperament has been studied in various researches and may be useful to
      predict how a child responds to dental treatment, especially very young children.
      The purpose of the present longitudinal study was to evaluate the behavioral
      manifestation of children aged 0 to 3 years, considering different types of
      dental situation. A total of 169 children were selected and the following data
      were collected: the age of the child, gender, age of the mother, number of dental
      visits and their respective dates, stimuli offered to the child, and behavioral
      response to these stimuli. The children and their respective behaviors were
      divided into five groups according to the dental situation offered: control,
      missed visits, fluoride varnish, restoration, and dental trauma. The data were
      submitted to descriptive and inferential analysis using the chi-square test, with
      the level of significance set at 5%. Analysis of the different situation offered
      to infants during routine dental care revealed a predominance of collaborating
      and partially collaborating behavior, and age at the time of dental care
      influenced the behavior of the infants, irrespective of the stimulus group. The
      different types of dental situation provoked changes in the behavioral response
      of the children of certain age groups, especially in the dental trauma group.

PMID- 19841546
TI  - Determinants for oral hygiene and periodontal status among mentally disabled
      children and adolescents.
AB  - AIM: To assess the impact of socio-demographic and clinical variables on the oral
      hygiene and periodontal status in a sample of mentally disabled subjects.
      MATERIALS AND METHODS: Study sample comprised of 171 mentally disabled subjects
      attending a special school in Udaipur, India. Oral hygiene status was assessed by
      Simplified Oral Hygiene Index (OHI-S) and periodontal status by Community
      Periodontal Index. RESULTS: Stepwise linear regression analysis revealed that the
      best predictors in the descending order for oral hygiene index were disabled
      sibling, medical diagnosis, IQ level, education of mother and father. Having Down
      syndrome, less educated parents, poor economic status and a disabled sibling were
      the most important predictors for poor periodontal status. CONCLUSIONS: The
      present study highlighted that the oral hygiene and periodontal status of the
      present study population is poor and was influenced by medical diagnosis, IQ
      level, disabled sibling, parent's level of education and economic status.

PMID- 19841547
TI  - A comparison of enameloplasty sealant technique with conventional sealant
      technique: a scanning electron microscope study.
AB  - CONTEXT: An accurate diagnosis of occlusal surface of permanent posterior teeth
      for the presence of caries is a challenge to the clinician, when using
      traditional explorer. This dilemma of hidden caries has led to invasively opening
      of the fissure before sealant placement. Enameloplasty is one such invasive
      procedure that has been implicated in the successful application of pit and
      fissure sealants. AIMS: The present study aims at evaluating the fissure
      micromorphology and sealant penetration under scanning electron microscope both
      with conventional sealant technique and enameloplasty sealant technique. SETTINGS
      AND DESIGN: The study comprised of extracted human posterior teeth subjected to
      enameloplasty of the fissures in the study groups as compared to unprepared
      fissures in the control groups. MATERIALS AND METHODS: The enameloplasty was
      performed with the help of specially designed Fissurotomy bur. The sealant used
      was Clinpro from 3M. All the samples were prepared for examination under scanning
      electron microscope. STATISTICAL ANALYSIS: A student 't' test was performed to
      compare the study and the control groups. RESULTS: (i) The surface area available
      for sealant placement on the occlusal surface was significantly increased
      following enameloplasty. (ii) Fissure width following enameloplasty was
      significantly increased. (iii) Extent of sealant penetration was significantly
      greater with enameloplasty sealant technique as compared to conventional sealant.
      CONCLUSION: Enameloplasty sealant technique can be preferred to conventional
      sealant technique for improving adhesion, adaptation and penetration of the
      sealant within the fissure system.

PMID- 19841548
TI  - Evaluation of caries experience in 3-6-year-old children, and dental attitudes
      amongst the caregivers in the Ludhiana city.
AB  - Early Childhood Caries (ECC) is a lifestyle disease that begins when the child's
      teeth erupt in the oral cavity. The distinctive pattern of decay rapidly spreads
      from one tooth to another and involves the surfaces of teeth that are usually not
      at risk. Detection of disease is crucial to control the oral condition using
      preventive and therapeutic regimes. The aim of this study was to determine the
      prevalence of caries in children of age 3-6 years in Ludhiana and to examine the
      relationship between age and caries experience. A total of 609 children in the
      age group of 3-6 years were examined using def index. To determine dental care
      seeking attitude, 105 caregivers were interviewed. Results revealed that 52.87%
      of children in the age group of 3-3.11 years, 45.1% of children in the age group
      of 4-4.11 years and 58.55% of children in 5-5.11 age groups suffered from caries.
      The mean def index was 1.82, 1.57 and 2.21, respectively. Interview of caregivers
      of children revealed that out of 105 only 12 (11.4%) children had previously been
      to a general dentist. None of them knew about Pedodontics as a specialty. The
      results of the present study can be used mainly for screening child populations
      in need of treatment, helping public workers and planners to develop dental
      health programs to aid early intervention and prevention.

PMID- 19841549
TI  - Juvenile aggressive ossifying fibroma of the maxilla.
AB  - Juvenile aggressive ossifying fibroma is an uncommon and controversial, benign
      but aggressive osteogenic neoplasm of the jaws commonly occurring in children and
      young adults. Complete removal of the tumor at the earliest possible stage is
      recommended owing to its high recurrence rate of 30-58%. Reported here is a case
      of recurrent juvenile aggressive ossifying fibroma of the maxilla in a 15-year
      old male treated with enucleation and curettage. A 10-month follow-up showed no
      signs of recurrence.

PMID- 19841550
TI  - Regional odontodysplasia in early childhood: a clinical and histological study.
AB  - Regional odontodysplasia (RO) is a rare disorder of dental development. The
      affected teeth are clinically hypoplastic and hypocalcified, presenting a ghost
      like appearance radiographically. The aim of this work was to report a clinical
      case of a child with both primary and permanent dentition affected by RO. The
      conducted therapy was based on a conservative approach, which consisted of follow
      up clinical evaluations of the anomalous teeth. However, the endodontic treatment
      of the primary incisors failed. Then, the chosen option for patient
      rehabilitation became extraction followed by removable of prosthesis confection.
      The extracted teeth were processed for histological analysis. In spite of the
      uncertain prognosis, but taking into account the psychological aspects of the
      patient, a conservative approach in an attempt to maintain those viable teeth in
      the oral cavity should be established.

PMID- 19841551
TI  - Foreign objects in teeth: retrieval and management.
AB  - The discovery of foreign bodies in the teeth is a special situation, which is
      often diagnosed accidentally. Detailed case history, clinical and radiographic
      examinations are necessary to come to a conclusion about the nature, size,
      location of the foreign body and the difficulty involved in its retrieval. It is
      more common to find this situation in children as it is a well-known fact that
      children often tend to have the habit of placing foreign objects in the mouth.
      Sometimes the foreign objects get stuck in the root canals of the teeth, which
      the children do not reveal to their parents due to fear. These foreign objects
      may act as a potential source of infection and may later lead to a painful
      condition. This paper discusses the types of foreign objects found in and around
      the teeth and reports two cases along with their retrieval and associated
      management of the involved teeth.

PMID- 19841552
TI  - Albright hereditary osteodystrophy: a rare case report.
AB  - Albright hereditary osteodystrophy (AHO) is a rare hereditary metabolic disorder
      that may be associated with or without resistant to parathyroid hormone
      (pseudohypoparathyroidism). It is commonly characterized by a constellation of
      physical features of short stature, round face, short neck, and small metacarpals
      and metatarsals, mild mental retardation, osteoporosis, subcutaneous
      calcification, and sometimes olfactory and hearing functional defect.
      Hypocalcaemia and hyperphosphatemia are the most important manifestations of the
      case. We report a clinical case of siblings with AHO with reduced Gs-alpha
      activity and we discuss their clinical features with oral manifestations,
      radiographic findings, laboratory tests along with treatment.

PMID- 19841553
TI  - Significance and prognostic impact of co-morbidity in head and neck cancer.

PMID- 19841554
TI  - Role of chelates in magnetic resonance imaging studies.
AB  - Imaging studies are tests performed with a variety of techniques that produce
      pictures of the inside of a patient's body. Magnetic resonance imaging (MRI) is
      an imaging technique based on the principles of nuclear magnetic resonance. MRI
      uses a powerful magnetic field, radio waves, and a computer to produce detailed
      pictures of organs, soft tissues, bone, and virtually all other internal body
      structures. Chelates have a wide application in such imaging techniques. Chelates
      in imaging studies are used alone as radioactive agents or conjugated to
      monoclonal antibodies or to DNA as radioactive agents. Technetium chelates and
      gadolinium chelates are being widely used as magnetic resonance contrast media.

PMID- 19841555
TI  - Surgery for malignant liver tumors.
AB  - Recent decades have witnessed an increase in liver resections. There is a need
      for an update on factors related to the management of liver tumors in view of
      newer published data. A systematic search using Medline, Embase, and Cochrane
      Central Register of Controlled Trials for the years 1983-2008 was performed. The
      IHPBA classification provides a suitable nomenclature of liver resections. While
      one randomized trial has provided an objective time of 30 min as optimal for
      intermittent pedicle occlusion, another randomized study has demonstrated the
      feasibility of performing liver resections without pedicle clamping. A randomized
      trial has demonstrated the benefit of clamp crushing over newer techniques of
      liver transection. Cohort studies support anatomical resections when feasible in
      terms of outcomes. Nonrandomized studies also support nonanatomical and ablative
      therapies in patients with cirrhosis and small remnant livers. A randomized trial
      has shown comparable long-term outcomes of radiofrequency ablation (RFA) and
      surgery for tumors < 5 cm. No randomized trials comparing laparoscopy and open
      surgery exist. Surgery remains an important treatment modality for malignant
      hepatic neoplasms. While anatomical resections provide improved survival, the
      choice of nonanatomical versus anatomical resections should be individualized
      taking into account factors such as cirrhosis and function of the liver remnant.
      A clear margin of resection is essential in all surgically resected cases. RFA is
      emerging as a useful, often complimentary tool, to surgery when dealing with
      complex tumors or tumors in patients with a poor liver function. Laparoscopic
      ultrasonography is useful in staging and performance of RFA.

PMID- 19841556
TI  - Reirradiation for progressive brain metastases.
AB  - Brain metastases constitute one of the most common distant metastases of cancer
      and are increasingly being detected with better diagnostic tools. The standard of
      care for solitary brain metastases with the primary disease under control is
      surgery followed by radiotherapy. Radiotherapy is also the primary modality for
      the treatment of multiple brain metastases, and improves both the quality of life
      and survival of patient. Unfortunately, more than half of these treated patients
      eventually progress leading to a therapeutic dilemma. Another course of
      radiotherapy is a viable but underutilized option. Reirradiation resolves
      distressing symptoms and has shown to improve survival with minimal late
      neurotoxicity. Reirradiation has conventionally been done with whole brain
      radiotherapy, but now studies with stereotactic radiosurgery have also shown
      promising results. In this review, we focus on reirradiation as a treatment
      modality in such patients. We performed a literature search in MEDLINE
      (www.pubmed.org) with key words brain metastases, reirradiation, whole brain
      radiotherapy, stereotactic radiosurgery, interstial brachytherapy, and brain. The
      search was limited to the English literature and human subjects.

PMID- 19841557
TI  - Preliminary results of SIB-IMRT in head and neck cancers: report from a regional
      cancer center in northern India.
AB  - BACKGROUND: Intensity-modulated radiotherapy using simultaneous integrated boost
      (SIB-IMRT) is an attractive method for the treatment of head and neck cancers
      with sparing of the salivary function. AIMS: To assess the feasibility, toxicity,
      and tumor control using SIB-IMRT in locally advanced head and neck cancers in the
      Indian setting. SETTINGS AND DESIGN: The study was conducted in a regional cancer
      center in northern India. A review of the treatment result of the first 20
      patients is presented. METHODS AND MATERIALS: SIB-IMRT was planned for 20
      patients--14 patients were treated with the SIB-72 schedule delivering a dose of
      72 Gy, 66 Gy, and 57 Gy to the PTV GTV , PTV CTV1 , and PTV CTV2 in 33 fractions.
      Six patients were treated with the SIB-66 schedule delivering 66 Gy, 60 Gy, and
      54 Gy to the above-mentioned volumes in 30 fractions. Patients were monitored for
      toxicity using the CTCAE v 3.0 criteria. Descriptive analysis of toxicity and
      actuarial estimates of the loco-regional control and survival are presented.
      RESULTS: Grade III mucositis was seen in 65% patients. None of the patients had
      Grade III dermatitis. The projected 2-year overall survival was 95%. CONCLUSION:
      SIB-IMRT schedules evaluated were found to be safe and effective and are being
      subjected to further prospective studies.

PMID- 19841558
TI  - Malignant melanoma: a retrospective series from a regional cancer center in
      India.
AB  - PURPOSE: To present our experience in treating malignant melanoma patients.
      METHODS AND MATERIALS: All melanoma patients treated at the Department of
      Radiotherapy, All India Institute of Medical Sciences, New Delhi, India, from
      1995 to 2007 were studied retrospectively. The endpoints were loco-regional
      recurrence, distant recurrence, recurrence-free survival (RFS), and duration of
      follow-up (DOFU). RFS and DOFU were analyzed with respect to the factors like
      age, sex, tissue of origin, site of disease, number of nodes, lymphadenopathy,
      ulceration, stage, and operability to find out any association. RESULTS: Seventy
      two patients were found evaluable with 40 males and 32 females (median age 46.5
      years). Eye was the commonest primary site with visual disturbance as the
      commonest symptom. Overall, 87% of the lesions were single, with most of the
      nonocular lesions presenting in the advanced stage. During the disease course,
      regional lymphadenopathy and distant metastases were seen in 33% and 32% of
      cases, respectively. Highest incidence of lymphadenopathy was seen in skin
      lesions and in primaries from trunk and extremities. Of all treated patients, 47%
      achieved complete response, 18% partial response, and others had either stable or
      progressive disease. The median DOFU was 6.2 months. RFS was studied only in
      curatively treated cases with a median of 10 months. Operability at presentation
      was the only prognostic factor influencing DOFU. CONCLUSION: Malignant melanoma
      is an uncommon disease in India carrying a lot of morbidity due to late
      presentation. Its management is still not clear regarding the optimum use and
      schedule of treatment modalities. More prospective studies in the future are
      required to come to a definite conclusion.

PMID- 19841559
TI  - Clinicopathological correlates of pediatric head and neck cancer.
AB  - BACKGROUND: The spectrum of head and neck tumors in children continues to be the
      cause of diverse, diagnostically challenging issues. AIMS: To demonstrate and
      compare the unique clinicopathological features in our study population and their
      correlations with the final histopathological diagnosis. METHODS: Fifty-three
      children with head and neck cancer were examined thoroughly at the
      Otorhinolaryngology department in a tertiary care teaching hospital followed by
      histopathological studies. RESULTS: Lymphomas were the most common malignant
      lesions seen followed by rhabdomyosarcomas, nasopharyngeal carcinomas, and others
      like thyroid carcinomas and eosinophilic granulomas. In the neck, the commonest
      cause of primary malignant disease was lymphoma; however, the most frequent
      lesion was reactive lymphadenitis. In the sinonasal region, the commonest
      malignancy was rhabdomyosarcoma, which often had extension to the orbit and the
      face. Recurrent epistaxis was found universally in the malignant cases of this
      region. In the facial region, disfiguring swelling with proptosis was mainly
      caused by rhabdomyosarcoma. The only case of tonsillar malignancy was due to non
      Hodgkin lymphoma. The duration of disease was less than 1 year. CONCLUSION: The
      most common manifestation of the malignant lesions in the pediatric age group was
      with a history of an enlarging, painless neck swelling. Still, an insignificant
      lump in the neck or recurrent bleeding from nose may be the manifestation of an
      underlying cancer.

PMID- 19841560
TI  - Micromultileaf collimator-based stereotactic radiosurgery for selected
      arteriovenous malformations: technique and preliminary experience.
AB  - PURPOSE: To report our experience of stereotactic radiosurgery (SRS) in
      consecutively treated patients with arteriovenous malformations (AVMs). MATERIALS
      AND METHODS: Of the 87 patients, 23 patients qualified and were treated with SRS
      as per predefined protocol according to AVM size, location, neurological status,
      prior bleeding, and the AVM score. All had Spletzer-Martin grade II/III and AVM
      scores <2.5. Patients underwent SRS using micromultileaf collimators delivering
      multiple noncoplanar fixed fields. Doses were prescribed using the Flickinger
      model. Patients were followed up with magnetic resonance angiography (MRA) and
      digitally subtracted angiography (DSA). RESULTS: The mean nidus volume was 3.65
      cc. The mean prescribed maximum dose was 22 Gy and the marginal dose was 19.24
      Gy; 12 Gy normal brain volume was 8.39 cc and 12 Gy marginal volume was 5.03 cc.
      Mean dose to brain stem, pituitary hypothalamic axis, and optic chiasm was 2.5,
      0.72, and 0.49 Gy, respectively. At a median follow-up of 22 months (range 1.5
      71.2 months), 7 of 10 patients presenting with a neurological deficit showed
      significant improvement. All 15 patients who underwent MRA 1.5-2 years after SRS
      had no residual nidus yielding an MRA complete obliteration rate of 100%. Twelve
      patients also underwent a check DSA, which confirmed obliteration in 11 of them
      resulting in an accuracy of MRA of 92%. One patient after SRS had transient
      deterioration of motor power, which resolved completely after a short course of
      steroids and another had mild worsening of the hemiparesis. All patients are able
      to lead an active functional life. CONCLUSIONS: Careful selection of cases
      suitable for SRS provides optimum obliteration rates with low toxicity.

PMID- 19841561
TI  - Treatment outcome with low-dose-rate interstitial brachytherapy in early-stage
      oral tongue cancers.
AB  - PURPOSE: Although radical radiotherapy is known to be equally effective for early
      stage oral tongue cancers (T1-2 N0) with the added advantage of organ and
      function preservation, surgery remains the preferred treatment. We present
      outcome of patients treated with brachytherapy (BT) either radical or boost.
      MATERIALS AND METHODS: Fifty-seven patients (T1/T2 31/26) were studied. Seventeen
      patients (30%) were treated with radical BT (50-67 Gy) while 40 (70%) with
      external beam radiation therapy (EBRT) + BT (36-56 Gy + 15-38 Gy]. Low-dose-rate
      (LDR) BT was delivered with 192 Ir wires, using plastic bead technique with
      varied dose rates (<60 cGy/h in 29 patients, 60-90 cGy/h in 17, and >90 cGy/h in
      11). RESULTS: The overall local control (LCR) was achieved in 59.7% (34/57)
      patients. LCR for T1 and T2 was 67.8% and 50%, respectively. A total of 23
      patients had failures [local: 20 (T1: 8; T2: 12 patients), node: 5 (T1:2; T2: 3),
      and local + nodal: 3]. Overall 5-year disease-free survival and overall survival
      (OAS) were 51% and 67%, respectively and those for T1 and T2 was 64.5/77.4% and
      38.5/54% respectively (P = 0.002). All 16 patients were salvaged. Median survival
      after salvage treatment was 13.5 months (6-100 months). Soft tissue necrosis was
      observed in 12.3% (7/57) and osteoradionecrosis in two patients. CONCLUSION: BT,
      as an integral part of radical radiation therapy in early-stage tongue cancers,
      appears to be an effective alternative treatment modality with preservation of
      the organ and function without jeopardizing the outcome.

PMID- 19841562
TI  - RET genetic screening in patients with medullary thyroid cancer: the Moroccan
      experience.
AB  - BACKGROUND: Germline RET gene mutations are well known to be the genetic causes
      of multiple endocrine neoplasia type 2 (MEN2) and may be identified by genetic
      screening. AIM: The purpose of the present study was to screen nine MTC patients
      for RET sequence changes. MATERIALS AND METHODS: In this study, our sample was
      composed of 30 individuals: 9 index patients with medullary thyroid carcinoma
      (MTC) corresponding either to 3 subjects with clinical evidence of MEN2, 6 with
      apparently sporadic MTC (sMTC), and 21 relatives have been investigated for RET
      mutations. After DNA extraction from peripheral blood leukocytes, RET exons 8,
      10, 11, 13-16 and exon/intron boundaries were analyzed by direct PCR sequencing.
      RESULTS: Three different known RET germline mutations in exon 11 (codon 634),
      p.Cys634Arg (c1900 T-->C) (de novo case), p.Cys634Phe (c1901 G-->T), p.Cys634Trp
      (c1902 C-->G), were detected in three individuals with MEN2 phenotype. Of the 21
      relatives, 2 cases presented mutation. Among the six probands with sMTC, none was
      found to carry mutation. There was no difference between RET polymorphisms
      detected among both MEN2 and sMTC patients. CONCLUSIONS: These preliminary data
      suggest that the RET mutation spectra observed in Moroccan patients with MEN2 are
      similar to those previously reported in other countries.

PMID- 19841563
TI  - Epitrochlear lymph node metastases from invasive ductal breast cancer.
AB  - Metastasis to an epitrochlear lymph node from a primary invasive breast cancer
      has not been reported earlier. We report a case of epitrochlear lymph node
      metastasis that presented 10 years after the primary breast malignancy had been
      treated with radiotherapy, chemotherapy, and hormonal therapy. The patient was
      successfully treated and continues to remain asymptomatic more than 2 years after
      she presented with the metastasis.

PMID- 19841564
TI  - Metachronous bilateral testicular germ cell tumors: report of two cases.
AB  - Metachronous bilateral testicular germ cell tumors is a rare known problem.
      However, no report of metachronus bilateralism was identified in the PubMed
      database published from India so far, where testicular cancer is relatively rare.
      We report the cases of two gentlemen. One had stage 1 nonseminomatous germ cell
      tumor (NSGCT) at the age of 32 in 1990 and developed marker relapse on
      surveillance and had chemotherapy using cisplatin and etoposide for four cycles.
      He developed contralateral seminoma in the testis 13 years later. Another patient
      had left orchidectomy in 2003 for NSGCT, had adjuvant BEP for two cycles, and
      developed a contralateral testicular tumor 5 years later, which was also
      seminoma. As more patients with germ cell tumors are cured with chemotherapy,
      long-term problems become important. Contralateral testicular tumor is one of
      them. As it can be very late, many years of continued follow-up examination and
      patients' awareness are necessary.

PMID- 19841565
TI  - Primary Ewing's sarcoma of the frontal bone with intracranial extension.
AB  - Primary Ewing's sarcoma arising from the skull is extremely rare. We report a
      case of an 11-year-old male child with primary Ewing's sarcoma of the frontal
      bone with intracranial extension. We also discuss the imaging and intraoperative
      findings and describe our use of a split calvarial graft in the present case.

PMID- 19841566
TI  - Oncogenous osteomalacia.
AB  - Oncogenous osteomalacia is a rare paraneoplastic renal phosphaturic condition,
      often associated with highly vascular benign mesenchymal tumors. We report a case
      of a 48-year-old male who presented with debilitating osteomalacia unresponsive
      to standard therapy. Two years later, sinonasal hemangiopericytoma was diagnosed;
      the patient underwent complete surgical excision with rapid symptomatic
      improvement.

PMID- 19841567
TI  - Spermatocytic seminoma with rhabdomyosarcomatous differentiation: a case report
      with a review of the literature.
AB  - Spermatocytic seminoma is an uncommon testicular germ cell tumor associated with
      a favorable outcome. Sarcomatous transformation in a spermatocytic seminoma is
      extremely rare with only 13 cases being reported in English literature. The
      presence of a sarcomatous component is associated with an aggressive behavior,
      metastasis, and poor prognosis. We present a case of a spermatocytic seminoma
      with rhabdomyosarcomatous transformation in a long-standing testicular swelling
      in a 55-year-old male.

PMID- 19841568
TI  - Invasive papillary carcinoma of the male breast: report of a rare case and review
      of the literature.
AB  - Breast masses occur in men far less commonly than women. Papillary lesions of the
      male breast are rare and comprise a spectrum of lesions ranging from benign
      intraductal papilloma to intraductal papillary carcinoma and invasive papillary
      carcinoma. In this case report, a 78-year-old man presented with a subareolar
      painless mass. Fine needle aspiration cytology (FNAC) was performed. Cytologic
      examination revealed a cellular aspirate. A diagnosis of papillary lesion
      favoring papillary carcinoma was rendered. The patient underwent modified radical
      mastectomy, which showed invasive papillary carcinoma. As far as we know, only a
      few cases of invasive papillary carcinoma of the male breast have been published
      in the literature. To the best of our knowledge, this is the first case report of
      invasive papillary carcinoma of male breast in Malaysia. In this purview, we
      discuss papillary carcinoma of male breast with review of the relevant
      literature.

PMID- 19841569
TI  - Turbid serum in a patient of acute lymphoblastic leukemia on treatment--what to
      look for?

PMID- 19841570
TI  - HIV and tuberculosis in Russia and eastern Europe: sounding the alarm.

PMID- 19841571
TI  - Cold spots in hot spots: transcription start sites of active genes are spared
      from HIV vector integration.
AB  - Recent studies on HIV integration in the human genome have reported on certain
      preferences for chromosomes, genes, or repetitive elements. We performed a high
      resolution meta-analysis of public available HIV vector insertion sites (n = 46
      114) and detected that HIV vectors significantly spared a region of 1 kb upstream
      and downstream to transcription start sites (TSS). Genes with the TSS being
      located within this 'insertional gap' had significantly lower expression levels
      than those with the TSS located outside the gap. Our data show an either
      unfavored and/or sterically inaccessible region located + or - 1 kb around TSS of
      transcriptionally active genes.

PMID- 19841573
TI  - Optimal image-guidance scenario with cone-beam computed tomography in
      conventionally fractionated radiotherapy for lung tumors.
AB  - PURPOSE: To determine the residual setup errors of several image guidance
      scenarios, using cone-beam computed tomography (CBCT) in conventionally
      fractionated radiotherapy for lung tumors. METHODS: Thirteen lung cancer patients
      were treated with conventionally fractionated radiotherapy, using daily image
      guidance with CBCT, resulting in 389 CBCT scans which were registered to the
      planning scan using automated soft-tissue registration. Using the resulting daily
      alignment data, 4 imaging frequency scenarios were analyzed: (A) no imaging; (B)
      weekly imaging with a 3-mm threshold; (C) first 5 fractions imaged, then weekly
      imaging with a patient-specific threshold; and (D) imaging every other day.
      RESULTS: The systematic setup error (Sigma) was reduced with increasing frequency
      of imaging from 3.4 mm for no imaging to 1.0 mm for imaging every other day.
      Random setup error (sigma), however, varied little regardless of the frequency of
      imaging: 2.9, 3.0, 3.4, and 3.2 mm for scenarios A, B, C, and D, respectively.
      The setup margins required to account for the residual error of each imaging
      scenario were 1 to 1.6 cm for scenario A, 4 to 6 mm for scenarios B and C, and 4
      to 5 mm for scenario D. As the residual error of daily CBCT was not included in
      this analysis, these margins compare with a margin of zero for daily CBCT.
      CONCLUSIONS: Daily image guidance is ideal as the setup margin can be reduced by
      about 5 mm versus a nondaily imaging scenario. However, if daily image guidance
      is not possible, there is little benefit in imaging more often than once a week.

PMID- 19841572
TI  - HIV-1 subtypes and differences in heterosexual HIV transmission among HIV
      discordant couples in Rakai, Uganda.
AB  - OBJECTIVE: To determine whether heterosexual transmission of HIV differs
      according to HIV-1 subtype. DESIGN: A retrospective observational cohort.
      METHODS: HIV-1 subtype effects on heterosexual HIV-1 transmission were determined
      among 268 HIV-discordant couples retrospectively identified from a population
      cohort in Rakai, Uganda. HIV-1 subtype (gag and gp41 sequencing and multiregion
      hybridization assay) and viral loads (reverse transcriptase PCR) were determined.
      Adjusted incidence rate ratios (adj IRR) of HIV transmission by subtype were
      estimated by multivariable Poisson regression adjusting for characteristics of
      index HIV-positive and HIV-negative partners. RESULTS: Adjusting for index HIV
      positive partners' age, viral load, stage of disease, genital ulcer disease, and
      HIV-negative partners' genital ulcer disease and nonuse of condoms, subtype A
      viruses were associated with a higher rate of transmission than subtype D
      [adj.IRR 1.98, 95% confidence interval (CI) 1.17-3.34], but no differences in
      transmission were observed between recombinant viruses and subtype D (aIRR 1.53,
      P = 0.25). Index-positive partners' age less than 30 years (adj.IRR 3.44, 95% CI
      1.75-6.78) and viral load (adj.IRR 2.37, 95% CI 1.75-3.21), and index-negative
      partners' genital ulcer disease (adj.IRR 1.71, 95% CI 1.08-2.70) and nonuse of
      condoms (adj.IRR 1.94, 95% CI 1.15-3.28) were significant determinants of HIV
      transmission. CONCLUSION: In Rakai, Uganda, subtype A viruses have a
      significantly higher rate of heterosexual transmission than subtype D viruses.
      Differential subtype transmission efficiency may be important for HIV vaccine
      evaluation and could contribute to subtype-specific HIV epidemics in sub-Saharan
      Africa.

PMID- 19841574
TI  - Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive
      chemoradiotherapy for locoregionally advanced esophageal cancer.
AB  - OBJECTIVE: To compare toxicities, disease control, and survival outcomes for
      patients treated with either cisplatin/irinotecan versus carboplatin/paclitaxel
      concurrent chemoradiotherapy for locally advanced esophageal cancer. METHODS:
      Single-institution retrospective comparison between treatment groups: the
      cisplatin/irinotecan group was treated with 2 cycles of induction chemotherapy
      followed by concurrent chemoradiotherapy, whereas the carboplatin/paclitaxel
      group began with chemoradiotherapy followed by 2 additional cycles of
      chemotherapy. Acute toxicities, response rates, disease control, survival
      outcomes, and patterns of failure were compared between the groups. RESULTS:
      Between January 2000 and December 2007, 57 patients were identified for inclusion
      in the present study (38 cisplatin/irinotecan and 19 carboplatin/paclitaxel).
      Groups were well-balanced by clinical-, pathologic-, staging-, and treatment
      related factors. Thirty-five patients (92%) in the cisplatin/irinotecan group and
      18 patients (95%) in the carboplatin/paclitaxel group completed the concurrent
      phase of chemoradiotherapy. There were no significant differences in hematologic
      or nonhematologic toxicities between the groups. At a median survivor follow-up
      of 37.6 months (range: 7.3-59.3 months) for the entire population, 22 patients
      were alive (16 without evidence of disease). The 3-year overall survival
      estimates was 19.7% for the cisplatin/irinotecan group versus 56.1% for the
      carboplatin/paclitaxel group (P = 0.022). Estimated 3-year cancer-specific
      survivals were 24.6% for the cisplatin/irinotecan group versus 59.3% for the
      carboplatin/paclitaxel group (P = 0.033). CONCLUSION: Concurrent
      chemoradiotherapy with carboplatin/paclitaxel is well-tolerated and provided
      superior overall and disease-specific survival compared with cisplatin/irinotecan
      chemoradiotherapy in the present study population. Further investigation is
      warranted.

PMID- 19841575
TI  - Ewing tumors of the head and neck.
AB  - PURPOSE: Retrospective review describing the 40-year University of Florida
      experience treating Ewing tumors of the head-and-neck region with a summary of
      the pertinent literature. PATIENTS AND METHODS: Nine patients were diagnosed and
      treated for Ewing sarcoma of the head and neck at our institution between 1965
      and 2007. Primary sites included: mandible (3 patients), calvarium (2 patients),
      paranasal sinus (2 patients), oral cavity (1 patient), and the extraosseous soft
      tissue of the neck (1 patient). The median age at diagnosis was 13.0 years
      (range, 6.3-20.1 years). The median observed follow-up was 10.2 years (range, 1.5
      37 years). RESULTS: All patients received multiagent chemotherapy and radiation
      therapy to a median dose of 55.8 Gy (range, 36-67.2 Gy). Three patients also
      underwent wide local excision. The actuarial 10-year overall survival, cause
      specific survival, event-free survival, and local control probabilities were 66%,
      66%, 56%, and 89%, respectively. Late complications included poor dentition, mild
      xerophthalmia, cataract, and mandibular hypoplasia. A literature search revealed
      8 previous series with Ewing tumors of the head and neck analyzed as subsets of
      larger studies. CONCLUSIONS: In the context of limited data on head and neck
      Ewing tumors, combined modality therapy provides excellent local control with
      reasonable acute and late toxicity. Large tumors were associated with poor
      disease control.

PMID- 19841576
TI  - Pulsed-dose-rate intracavitary brachytherapy for cervical carcinoma: the AIIMS
      experience.
AB  - OBJECTIVE: The aim of present study was to analyze the results of pulsed-dose
      rate (PDR) brachytherapy in patients with cervical carcinoma treated at our
      center. METHODS: From September 2003 to September 2005, 48 patients with
      histopathologically proved cervical carcinoma, stages IB to IVA, were treated
      with PDR intracavitary radiotherapy (ICRT) and pelvic irradiation at our center.
      Radiotherapy consisted of whole pelvis external beam radiation therapy (EBRT)
      with a dose of 40 Gy in 22 fractions over 4.5 weeks followed by 10 Gy in 5
      fractions over 1 week with midline shielding. Weekly chemotherapy (Cisplatin, 40
      mg/m) was administered during the course of EBRT to suitable patients. After an
      interval of 1 to 2 weeks, a single session of standard ICRT application was done
      to deliver a dose of 27 Gy to point A by PDR (hourly pulse, 70 cGy). RESULTS:
      Median age was 50 years (range: 30-65). FIGO stage distribution of the patients
      was as follows: stage IB, 6; stage IIA, 1; stage IIB, 15; stage IIIB, 25; and
      stage IVA, 1. Follow-up period ranged from 3 to 50 months (median: 15 months).
      Ten patients had disease recurrence (5 each in stage IIB and stage IIIB). Eight
      patients had pelvic failure, 1 had bone metastases, and 1 had supraclavicular
      node metastases. Overall grades III to IV late toxicity rate at 50 months was 6%.
      For the median follow-up period of 15 months, the actuarial recurrence-free
      survival in stages I to II was 82% and stages III to IV was 78%. CONCLUSION: Our
      results reveal that PDR ICRT in combination with pelvic EBRT provides excellent
      pelvic disease control, survival, and low radiation related morbidity rate in the
      patients with cervical carcinoma.

PMID- 19841577
TI  - Mutation analysis in primary immunodeficiency diseases: case studies.
AB  - PURPOSE OF REVIEW: The application of mutation analysis is becoming an integral
      part of the complete evaluation of patients with primary immunodeficiencies, and
      as such, clinicians caring for these patients must develop a better understanding
      of the utility and challenges of this important laboratory technology. RECENT
      FINDINGS: Genomic DNA sequencing is currently the standard approach used to
      characterize a possible gene mutation causing a specific primary
      immunodeficiency. There are clinical situations in which this approach is
      revealing of a genetic defect and other circumstances in which this generates a
      false-positive or false-negative result. One case study is presented that reviews
      a straightforward analysis that clarifies the genetic basis of a primary
      immunodeficiency, and four cases are presented that required additional studies
      to clarify the underlying basis of the immunodeficiency. In the latter
      circumstances, the rationale for additional studies is outlined and the outcome
      of these is presented. SUMMARY: The identification of a gene mutation as the
      underlying basis of a primary immunodeficiency begins with the evaluation of the
      clinical presentation focusing on the infection history so as to develop a
      differential diagnosis including potential genetic causes. The next step is to
      obtain specific laboratory studies, including immunologic function evaluation,
      and, based on these findings, to proceed with DNA sequencing of one or several
      selected candidate genes. Genomic DNA sequencing has certain limitations, and
      alternative follow-up approaches may be necessary to establish the molecular
      basis of the primary immunodeficiency in a given patient.

PMID- 19841579
TI  - Obesity in older adults: relationship to functional limitation.
AB  - PURPOSE OF REVIEW: The present review is intended to provide a critical overview
      of recent investigations of obesity among older persons with emphasis upon
      associated functional limitations, potential for intervention, and a future
      research agenda. RECENT FINDINGS: Obesity is growing in prevalence among older
      persons. The association between obesity and functional decline is well
      documented. Recent findings suggest possible contributions of obesity-associated
      inflammatory milieu, sarcopenia, and impairment of muscle function/strength to
      adverse functional outcomes. A growing body of literature supports consideration
      of moderate weight reduction to secure improved metabolic and functional
      parameters for obese older persons. SUMMARY: Obesity is associated with an
      unfortunate burden of chronic disease, functional limitation, and poor life
      quality. In view of the growing numbers of afflicted older individuals, there
      must be research priority to discern how obesity impacts function so that
      appropriate prevention and treatment strategies may be adopted.

PMID- 19841578
TI  - Thymus microenvironment in human primary immunodeficiency diseases.
AB  - PURPOSE OF REVIEW: Severe combined immunodeficiencies represent a heterogeneous
      group of genetic disorders affecting genes of both early and late steps in
      lymphocytes development, a process tightly controlled by thymic epithelial cells.
      Detailed analysis of thymic morphology aids to the assessment of the severity of
      the immune disorder and may be critical to the understanding of the role of the
      genetic defects in the pathophysiology of these diseases. In this review, we
      highlight recent advancements in the characterization of the thymic
      microenvironment in primary immunodeficiencies. RECENT FINDINGS: Crosstalk
      between thymocytes and thymic epithelial cells is essential to preserve thymic
      architecture and function, and therefore to promote T-cell maturation and
      development of self-tolerance. Early severe defects in T-cell development result
      in profound abnormalities of thymic epithelial cells differentiation with loss of
      AIRE expression and severe reduction of thymic dendritic and T-regulatory cells.
      Differently, later defects in T-cell development that are permissive for normal
      thymocytes development allow cortico-medullary differentiation with partially
      preserved AIRE expression and dendritic/T-regulatory cells distribution.
      Hypomorphic mutations in the same genes partially permissive to T-cell
      development may result in a more complex phenotype with immunodysreactivity and
      peculiar thymic alterations. SUMMARY: Although the molecular and genetic bases of
      primary immunodeficiencies directly aid to both diagnosis and management of the
      patients, the detailed analysis of thymic morphology critically contributes to
      unveil the pathophysiology of these diseases.

PMID- 19841580
TI  - Age-related macular degeneration and antioxidant vitamins: recent findings.
AB  - PURPOSE OF REVIEW: The purpose of the present review is to evaluate the most
      recent evidence for a role of antioxidant nutrients in the prevention or delay in
      progression of age-related macular degeneration (AMD), a major cause of visual
      impairment and blindness in the aging population. RECENT FINDINGS: Recent human
      studies (>2008) report a decreased AMD risk with increased intakes of
      lutein/zeaxanthin, B vitamins, zinc and docosahexaenoic acid but an increased
      risk with increased intakes of beta-carotene and vitamin E. These latter findings
      are inconsistent with previous reports (<2008). SUMMARY: Findings on the
      association of certain antioxidants and docosahexaenoic acid support a role for
      nutrition in a decreased risk of AMD. The inconsistent findings of an increased
      risk with increased intake of beta-carotene and vitamin E warrants continued
      investigation into these relationships.

PMID- 19841581
TI  - Evidence that protein requirements have been significantly underestimated.
AB  - PURPOSE OF REVIEW: This review discusses recent evidence that suggests a
      significant underestimation of protein requirements in adult humans. RECENT
      FINDINGS: Traditionally, total protein requirements for humans have been
      determined using nitrogen balance. The recent Dietary Reference Intake
      recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day,
      respectively, of high-quality protein in adult humans are based on a meta
      analysis of nitrogen balance studies using single linear regression analysis. We
      reanalyzed existing nitrogen balance studies using two-phase linear regression
      analysis and obtained mean and safe protein requirements of 0.91 and 0.99
      g/kg/day, respectively. The two-phase linear regression analysis is considered
      more appropriate for biological analysis of dose-response curves. Considering the
      inherent problems associated with the nitrogen balance method, we developed an
      alternative method, the indicator amino acid oxidation technique, to determine
      protein requirements The mean and population-safe requirements in adult men were
      determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher
      than the current Dietary Reference Intakes recommendations. SUMMARY: The
      indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g
      protein/kg/day and the reanalysis of existing nitrogen balance studies are
      significantly higher than current recommendations. Therefore, there is an urgent
      need to reassess recommendations for protein intake in adult humans.

PMID- 19841583
TI  - Effect of physical activity on glutamine metabolism.
AB  - PURPOSE OF REVIEW: Glutamine is largely synthesized in skeletal muscles and
      provides fuel to rapidly dividing cells of the immune system and precursors to
      gluconeogenesis in the liver. Physical exercise is known to affect glutamine
      synthesis and to modulate glutamine uptake. Overtraining is frequently associated
      with reduced availability of glutamine and decreased immunocompetence. Inactivity
      affects glutamine metabolism, but this subject was poorly investigated. RECENT
      FINDINGS: Strenuous physical exercise as well as exhaustive training programs
      lead to glutamine depletion due to lowered synthesis and enhanced uptake by liver
      and immune cells. Evidence suggests that postexercise glutamine depletion is
      associated with immunodepression. Counterwise, moderate training leads to
      improved glutamine availability due to a positive balance between muscle
      synthesis and peripheral clearance. Physical inactivity, as investigated by
      experimental bed rest in healthy volunteers, reduced glutamine synthesis and
      availability. SUMMARY: After exercise, a reduced glutamine availability may be
      considered as a marker of overtraining. An increased glutamine availability may
      contribute to decreased inflammation and health benefits associated with optimal
      training. Thus, glutamine supplementation may enhance immunocompetence after
      strenuous exercise. The potential of glutamine supplementation during physical
      inactivity needs to be explored.

PMID- 19841582
TI  - Regulation of nitric oxide production in health and disease.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent publications
      examining nitric oxide production in health and disease and its association with
      clinical nutrition and alterations in metabolism. RECENT FINDINGS: The role of
      the cofactor tetrahydrobiopterin in nitric oxide production and its relation with
      arginine availability is indicated as an important explanation for the arginine
      paradox. This offers potential for nitric oxide regulation by dietary factors
      such as arginine or its precursors and vitamin C. Because diets with a high
      saturated fat content induce high plasma fatty acid levels, endothelial nitric
      oxide production is often impaired due to a reduction in nitric oxide synthase 3
      phosphorylation. Increasing the arginine availability by arginine therapy or
      arginase inhibition was, therefore, proposed as a potential therapy to treat
      hypertension. Recent studies in septic patients and transgenic mice models found
      that inadequate de-novo arginine production from citrulline reduces nitric oxide
      production. Citrulline supplementation may, therefore, be a novel therapeutic
      approach in conditions of arginine deficiency. SUMMARY: Both lack and excess of
      nitric oxide production in diseases can have various important implications in
      which dietary factors can play a modulating role. Future research is needed to
      expand our understanding of the regulation and adequate measurement of nitric
      oxide production at the organ level and by the different nitric oxide synthase
      isoforms, also in relation to clinical nutrition.

PMID- 19841584
TI  - New approaches for quantitating the inhibition of HIV-1 replication by antiviral
      drugs in vitro and in vivo.
AB  - PURPOSE OF REVIEW: With highly active antiretroviral therapy, HIV-1 infection has
      become a manageable lifelong disease. Developing optimal treatment regimens
      requires understanding how to best measure anti-HIV activity in vitro and how
      drug dose-response curves generated in vitro correlate with in-vivo efficacy.
      RECENT FINDINGS: Several recent studies have indicated that conventional
      multiround infectivity assays are inferior to single cycle assays at both low and
      high levels of inhibition. Multiround infectivity assays can fail to detect
      subtle but clinically significant anti-HIV activity. The discoveries of the anti
      HIV activity of the hepatitis B drug entecavir and the herpes simplex drug
      acyclovir were facilitated by single-round infectivity assays. Recent studies
      using a single-round infectivity assay have shown that a previously neglected
      parameter, the dose-response curve slope, is an extremely important determinant
      of antiviral activity. Some antiretroviral drugs have steep slopes that result in
      extraordinary levels of antiviral activity. The instantaneous inhibitory
      potential, the log reduction in infectivity in a single-round assay at clinical
      drug concentrations, has been proposed as a novel index for comparing antiviral
      activity. SUMMARY: Among in-vitro measures of antiviral activity, single-round
      infection assays have the advantage of measuring instantaneous inhibition by a
      drug. Re-evaluating the antiviral activity of approved HIV-1 drugs has shown that
      the slope parameter is an important factor in drug activity. Determining the
      instantaneous inhibitory potential by using a single-round infectivity assay may
      provide important insights that can predict the in-vivo efficacy of anti-HIV-1
      drugs.

PMID- 19841585
TI  - BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical
      implications.
AB  - PURPOSE OF REVIEW: To summarize evidence on the prevalence and spectrum of BRCA1
      and BRCA2 BRCA1/2 mutations across racial and ethnic groups and discuss
      implications for clinical practice. RECENT FINDINGS: The prevalence of BRCA1/2
      mutations is comparable among breast cancer patients of African, Asian, white,
      and Hispanic descent: approximately 1-4% per gene. Among ovarian cancer patients
      in North America, BRCA1/2 mutations are present in 13-15%. Between racial/ethnic
      groups, there are important differences in the spectrum of BRCA1 compared with
      BRCA2 mutations, in BRCA1/2 variants of uncertain significance, and in the
      accuracy of clinical models that predict BRCA1/2 mutation carriage. SUMMARY:
      Given the significant prevalence of BRCA1/2 mutations across race/ethnicity,
      there is a need to expand and customize genetic counseling, genetic testing, and
      follow-up care for members of all racial/ethnic groups.

PMID- 19841586
TI  - Editorial boards: where are all the women?

PMID- 19841587
TI  - Changes in the use of HIV antiretroviral resistance testing in a large cohort of
      U.S. patients, 1999 to 2006.
AB  - INTRODUCTION: Monitoring antiretroviral (ARV) drug resistance is of growing
      importance in the management of persons infected with HIV, but few reports
      document how genotypic and phenotypic resistance testing (GPT) has been used
      among patients receiving routine outpatient care. METHODS: We studied data from
      participants in the HIV Outpatient Study seen at 10 HIV clinics in the United
      States during 1999 to 2006. We restricted analyses to patients whom we considered
      eligible for GPT (i.e., had a documented HIV viral load >1000 copies/mL). We used
      multivariable general modeling to evaluate temporal trends in use of GPT among
      eligible patients and to identify factors associated with being tested during
      1999 to 2002 and 2003 to 2006. RESULTS: Of 5594 active patients, 3995 (71%) were
      considered eligible for GPT in at least one year during 1999 to 2006 (declining
      from 50.2% in 1999 to 31.2% in 2006). The fraction of eligible patients receiving
      GPT increased from 11.2% in 1999 to 31.0% in 2003 (P < 0.001 for trend) and then
      stabilized at approximately 30% through 2006. Among persons tested, the annual
      percentage receiving only genotype testing declined over time (90% to 56%),
      whereas the percentage receiving genotype and phenotype testing increased (5.4%
      to 39.1%). The annual use of GPT for ARV-naive patients increased over time and
      after 2003 exceeded the corresponding rates for ARV-experienced patients. In
      multivariable analyses, low CD4 count and high HIV viral load were consistently
      associated with GPT. Compared with other ARV-experienced patients, those who were
      triple ARV-class experienced were consistently more likely to be tested, whereas
      ARV-naive were less likely to be tested during 1999 to 2002 and more likely
      during 2003 to 2006. In addition, women and heterosexual men (vs. men who have
      sex with men) and black patients (vs. white) were less likely to be tested during
      1999 to 2002, whereas older patients were less likely to be tested during 2003 to
      2006. DISCUSSION: The annual frequency of GPT use has increased almost threefold
      since 1999. GPT use among ARV-naive patients has increased coincident with
      dissemination of recommendations. Although earlier sex and racial/ethnic
      disparities in testing have waned, older patients were significantly less likely
      to be tested in recent years.

PMID- 19841588
TI  - Two distinct epidemics: the rise of HIV-1 and decline of HIV-2 infection between
      1990 and 2007 in rural Guinea-Bissau.
AB  - OBJECTIVES: To assess changes in HIV incidence and prevalence in Caio, a rural
      area of Guinea-Bissau, between 1990 and 2007. DESIGN: Three cross-sectional
      community surveys. METHODS: In 1990, 1997, and 2007, surveys were conducted among
      adults. The prevalence of HIV-1 and of HIV-2 was estimated for each survey, and
      incidence rates were calculated for the first (1990-1997) and second period (1997
      2007). RESULTS: The HIV-1 incidence was approximately 4.5/1000 person-years in
      the two periods, whereas the HIV-2 incidence decreased from 4.7 (95% confidence
      interval 3.6-6.2) in the first to 2.0 (95% confidence interval 1.4-3.0) per 1000
      person-years in the second period (P < 0.001). HIV-1 prevalence rose from 0.5% in
      1990 to 3.6% in 2007, and HIV-2 prevalence decreased from 8.3% in 1990 to 4.7% in
      2007. HIV-1 prevalence was less than 2% in 15 to 24 year olds in all surveys and
      was highest (7.2%) in 2007 among 45 to 54 year olds. The HIV-2 prevalence was
      fivefold higher in older subjects (> or =45 yr) compared with those less than 45
      years in both sexes in 2007. CONCLUSIONS: HIV-1 incidence is stable, and its
      prevalence is increasing, whereas HIV-2 incidence and prevalence are both
      declining. In contrast with what has been observed in other sub-Saharan
      countries, HIV-1 prevalence is lower in younger age groups than older age groups.

PMID- 19841589
TI  - Inpatient health services utilization among HIV-infected adult patients in care
      2002-2007.
AB  - OBJECTIVE: This study examines the frequency of inpatient hospitalization, the
      number of inpatient days, and factors associated with inpatient utilization in a
      multistate HIV cohort between 2002 and 2007. DESIGN: A prospective cohort study
      of HIV-infected adults in care at 11 US HIV primary and specialty care sites
      located in different geographic regions. METHODS: Demographic, clinical, and
      resource utilization data were collected from medical records for the years 2002
      2007. Rates of resource use were calculated for number of hospital admissions,
      total inpatient days, and mean length of stay per admission. RESULTS: Annual
      inpatient hospitalization rates significantly decreased from 35 to 27 per 100
      persons from 2002 to 2007. The number of inpatient days per year significantly
      decreased over time, whereas mean length of stay per admission was stable. Women,
      patients 50 years or older, blacks, injection drug users, and patients without
      private insurance had higher hospitalization rates than their counterparts.
      Admission rates were lower for patients with high CD4 counts and low HIV-1 RNA
      levels. CONCLUSIONS: Inpatient hospitalization rates and number of inpatient days
      decreased for HIV patients in this multistate cohort between 2002 and 2007.
      Sociodemographic disparities in inpatient utilization persist.

PMID- 19841591
TI  - Echo/Doppler-derived time intervals are able to predict left ventricular reverse
      remodeling after cardiac resynchronization therapy.
AB  - AIM: We evaluated the predictive value of echo/Doppler derived indices, which
      reflect the duration of the isovolumic phases of the cardiac cycle, in
      identifying cardiac resynchronization therapy (CRT) responders. METHODS AND
      RESULTS: In 105 patients before and 6 months after CRT the following echo/Doppler
      parameters were evaluated: myocardial performance index (MPI) as the sum of
      isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) divided
      by ejection time; total isovolumic time (t-IVT) as the sum of IVCT and IVRT
      divided by the RR interval; and standard deviation of the time to systolic peak
      velocity (Ts-SD) as asynchrony index. After 6 months, patients were defined
      responders according to 15% left ventricle (LV) end-systolic volume reduction or
      more. At baseline, responders (53.3%) had higher t-IVT and MPI than nonresponders
      (0.30 +/- 0.06 versus 0.22 +/- 0.05, P < 0.0001 and 1.01 +/- 0.27 versus 0.73 +/-
      0.19, P < 0.0001, respectively). Receiving operating characteristic curve
      analysis showed that both t-IVT (80.3% sensitivity and 83.7% specificity, cut-off
      = 0.263) and MPI (78.6% sensitivity and 81.6% specificity, cut-off = 0.84) could
      predict CRT response. Baseline t-IVT correlated well to end-systolic volume
      reduction (r = -0.56, P < 0.00001). CONCLUSION: Echo/Doppler derived indices,
      describing physiologic abnormalities of the isovolumic contraction and relaxation
      phase, are able to predict CRT-induced reverse remodeling.

PMID- 19841590
TI  - Implementation of raltegravir in routine clinical practice: selection criteria
      for choosing this drug, virologic response rates, and characteristics of
      failures.
AB  - BACKGROUND: Raltegravir (RAL) achieved remarkable virologic suppression rates in
      randomized-clinical trials, but today efficacy data and factors for treatment
      failures in a routine clinical care setting are limited. METHODS: First, factors
      associated with a switch to RAL were identified with a logistic regression
      including patients from the Swiss HIV Cohort Study with a history of 3 class
      failure (n = 423). Second, predictors for virologic outcome were identified in an
      intent-to-treat analysis including all patients who received RAL. Last
      observation carried forward imputation was used to determine week 24 response
      rate (HIV-1 RNA >or= 50 copies/mL). RESULTS: The predominant factor associated
      with a switch to RAL in patients with suppressed baseline RNA was a regimen
      containing enfuvirtide [odds ratio 41.9 (95% confidence interval: 11.6-151.6)].
      Efficacy analysis showed an overall response rate of 80.9% (152/188), whereas
      71.8% (84/117) and 95.8% (68/71) showed viral suppression when stratified for
      detectable and undetectable RNA at baseline, respectively. Overall CD4 cell
      counts increased significantly by 42 cells/microL (P < 0.001). Characteristics of
      failures were a genotypic sensitivity score of the background regimen <or=1, very
      low RAL plasma concentrations, poor adherence, and high viral load at baseline.
      CONCLUSIONS: Virologic suppression rates in our routine clinical care setting
      were promising and comparable with data from previously published randomized
      controlled trials.

PMID- 19841592
TI  - Coronary angiography and computed tomography angiography in the diagnosis of
      extrinsic compression of left internal mammary artery.

PMID- 19841593
TI  - Prediction of clinical and mucosal severity of coeliac disease and dermatitis
      herpetiformis by quantification of IgA/IgG serum antibodies to tissue
      transglutaminase.
AB  - OBJECTIVES: We analysed whether the quantification of autoantibodies against
      tissue transglutaminase could be used to predict mucosal destruction and disease
      severity in patients with gluten sensitivity. PATIENTS AND METHODS: One hundred
      seventy patients with coeliac disease (CD), comprising 52 children with severe
      malabsorption (group I), 59 children with mild symptoms (group II), 59 adults
      (group III), 134 patients with dermatitis herpetiformis (DH), and 131 disease
      controls, were studied. Serial serum samples of patients in groups I and II on a
      gluten-free diet were also included. Serum levels of antibodies against
      recombinant tissue transglutaminase were determined with ELISA using standard
      curves for quantification of antibodies. RESULTS: Immunoglobulin (Ig)A antibodies
      against tissue transglutaminase (IgA-TGA) were detected in all of the patients
      with CD and in 95% of the DH patients. The IgA-TGA and IgG-TGA levels were higher
      in group I (P < 0.001). The IgG-TGA levels and positivity rate in group I (100%)
      were higher than in group II (81%), group III (73%), and the DH group (67%).
      Elevated IgA-TGA and IgG-TGA levels in combination predicted a more severe small
      intestinal atrophy (P < 0.0001) with a specificity of 99% for Marsh IIIb-IIIc
      (flat) lesions. The kinetics of the IgA-TGA decrease during diet differed between
      groups I and II. CONCLUSIONS: High levels of IgA-TGA and IgG-TGA antibodies were
      associated with the grade of mucosal villous atrophy and a more severe clinical
      presentation. The combined measurement of IgA-TGA and IgG-TGA enables a
      noninvasive prediction of small intestinal villous atrophy with high accuracy,
      and may reduce the need for a biopsy in patients with suspected CD.

PMID- 19841594
TI  - Oropharyngeal and proximal esophageal involvement during adalimumab treatment of
      Crohn disease.

PMID- 19841595
TI  - Association of gastric heterotopic pancreas and esophageal atresia in children.
AB  - OBJECTIVES: Esophageal atresia with or without tracheo-esophageal fistula is a
      frequent malformation that occurs in about 1 of 3000 live births. It can be
      associated with other congenital malformations. The aim of this study was to
      measure the frequency of heterotopic pancreas (HP) in children with esophageal
      atresia (EA) and to evaluate possible linkage with other malformations. MATERIALS
      AND METHODS: All patients with EA were prospectively followed since 2005 at
      Hopital Sainte-Justine and since 2006 at the Montreal Children's Hospital. We
      compared 91 patients who underwent gastroscopy during that period with 182
      control patients who submitted to gastroscopy for other indications. The presence
      or the absence of HP and its localization were noted in both groups. The
      following data were also collected on patients with EA: sex, gestational age, EA
      type, and other malformations. RESULTS: Seventeen (18.7%) of the 91 patients with
      EA had gastric HP compared with 1 (0.5%) in the control group (OR 42, 95%
      confidence interval 7-249, P < 0.001). There were no differences between patients
      with or without HP regarding sex, prematurity, EA type, and the presence or
      absence of other congenital abnormalities. CONCLUSIONS: This study demonstrates,
      for the first time, that gastric HP is associated with EA irrespective of other
      malformations.

PMID- 19841596
TI  - Variceal bleeding in an adolescent with HIV diagnosed with hepatoportal sclerosis
      and nodular regenerative hyperplasia.

PMID- 19841597
TI  - Listeria meningitis after infliximab treatment of ulcerative colitis.

PMID- 19841598
TI  - Celiac disease and eosinophilic esophagitis: a true association.
AB  - BACKGROUND AND AIM: Celiac disease (CD) and eosinophilic esophagitis (EE) are
      distinct disorders with specific clinico-pathological characteristics. Recent
      reports suggest an association between the 2. The aim of this study was to
      estimate the prevalence of EE among children diagnosed with CD in our institution
      in the last 8 years. MATERIALS AND METHODS: Princess Margaret Hospital in Western
      Australia is the state's only pediatric referral center and the Department of
      Anatomic Pathology handles almost all of the pediatric gastrointestinal biopsy
      specimens. All of the children who had histological confirmation of CD between
      January 2000 and November 2007 were identified. Among this cohort, those who had
      concurrent esophageal biopsies performed were obtained and those with histology
      consistent with EE identified. The slides of all of these cases were reviewed.
      Case notes of children with CD and EE were reviewed for demographic details,
      symptoms, endoscopic findings, and follow-up data. RESULTS: Among the total of
      250 children diagnosed with CD during the study period, 121 had concurrent
      esophageal biopsies. Ten children had histological findings consistent with EE,
      although only 7 had endoscopic findings suggestive of EE. Median eosinophil count
      in these esophageal biopsies was 52 per high power field (range 23-80). Four
      children had follow-up endoscopies and all 4 demonstrated recovery of duodenal
      mucosa but persistent esophageal eosinophilia on gluten-free diet. In 3 children
      resolution of EE occurred after specific treatment of EE. CONCLUSIONS: The
      prevalence of EE in this cohort of children with CD is at least 4%. This is
      likely to be an underestimation because only 121 of 250 children had concurrent
      esophageal biopsies. Coexistent EE should be kept in mind in children undergoing
      endoscopy for suspected CD, and esophageal biopsies should be obtained,
      irrespective of whether esophageal mucosa appears normal or abnormal at
      endoscopy.

PMID- 19841599
TI  - Synaptic capture-mediated long-lasting long-term potentiation is strongly
      dependent on mRNA translation.
AB  - In the CA1 region of mice hippocampal slices, a strong tetanic stimulation of an
      input pathway triggers a long-lasting long-term potentiation (L-LTP), which
      requires protein synthesis for the development of its late phase. A weak tetanic
      stimulation of one pathway, which is incapable of triggering protein synthesis on
      its own, can nonetheless induce L-LTP if it is preceded by a strong stimulation
      of another pathway (synaptic capture-mediated L-LTP). We found that anisomycin
      (25 microM), a translational inhibitor, impaired the strong stimulation-induced L
      LTP more severely when the drug was applied during the whole experiment than when
      delivered only around the induction period. Taking advantage of this phenomenon,
      we showed that the synaptic capture-mediated L-LTP was strongly dependent on mRNA
      translation.

PMID- 19841600
TI  - Evaluation of round window stimulation using the floating mass transducer by
      intracochlear sound pressure measurements in human temporal bones.
AB  - HYPOTHESIS: Round window (RW) stimulation with a floating mass transducer (FMT)
      can be studied experimentally and optimized to enhance auditory transduction.
      BACKGROUND: The FMT (MED-EL Vibrant Soundbridge) has been recently implanted in
      patients with refractory conductive or mixed hearing loss to stimulate the RW
      with varying degrees of success. The mechanics of RW stimulation with the FMT
      have not been studied in a systematic manner. METHODS: In cadaveric human
      temporal bones, measurements of stapes velocity with laser vibrometry in response
      to FMT-RW stimulation were used to optimize FMT insertion. The effect of RW
      stimulation on hearing was estimated using simultaneous measurements of
      intracochlear pressures in both perilymphatic scalae with micro-optical pressure
      transducers. This enabled calculation of the differential pressure across the
      cochlear partition, which is directly tied to auditory transduction. RESULTS: The
      best coupling between the FMT and RW was achieved with a piece of fascia placed
      between the RW and the FMT, and by "bracing" the free end of the FMT against the
      hypotympanic wall with dental impression material. FMT-RW stimulation provided
      differential pressures comparable with sound-induced oval window stimulation
      greater than 1 kHz. However, less than 1 kHz, the FMT was less capable.
      CONCLUSION: Measurements of stapes velocity and intracochlear sound pressures in
      scala vestibuli and scala tympani enabled experimental evaluation of FMT
      stimulation of the RW. The efficacy of FMT-RW coupling was influenced
      significantly by technical and surgical factors, which can be optimized. This
      temporal bone preparation also lays the foundation for future studies to
      investigate multiple issues of relevance to both basic and clinical science such
      as RW stimulation in stapes fixation, nonaerated middle ears, and third-window
      lesions, and to answer basic questions regarding bone conduction.

PMID- 19841601
TI  - Spectrum of hearing disorders and their management in children with CHARGE
      syndrome.
AB  - OBJECTIVE: The CHARGE syndrome is associated with ear anomalies and deafness in
      addition to other malformations. Deformations of the ossicles or aplasia of the
      semicircular canals, cochlear hypoplasia, hypoplasia or aplasia of the VIIIth
      cranial nerve and abnormal routing of the VIIth cranial nerve, sigmoid sinus, and
      emissaries are typical findings. The aim of this study is to explore the
      feasibility and procedure of cochlear implantation in patients with CHARGE
      syndrome and to assess the outcome. STUDY DESIGN: Retrospective case review.
      SETTING: Tertiary referral center; cochlear implant program. PATIENTS: Ten
      patients with CHARGE syndrome and 3 patients with CHARGE-like syndrome treated in
      our center due to hearing impairment. Eleven patients were congenitally deaf, 1
      patient had progressive hearing loss, and 1 patient had mixed hearing loss.
      INTERVENTION: Computed tomography of temporal bones and magnetic resonance
      imaging of the brain; bone-anchored hearing aid surgery, cochlear implantation,
      rehabilitation results. MAIN OUTCOME MEASURES: Surgical suitability and hearing
      rehabilitation. RESULTS: We illustrate the management of preoperative
      diagnostics, surgical planning, and hearing rehabilitation. One patient with
      mixed hearing loss underwent bilateral bone-anchored hearing aid surgery. Because
      2 patients had bilateral aplasia of the auditory nerves, we recommended an
      auditory brainstem implant. The unilateral cochlear implantation was performed in
      9 patients and bilateral in 1 patient. In selected cases, it was helpful to plan
      the operation using a simulator for temporal bone surgery. Complex malformations,
      such as in CHARGE syndrome, with an increased intraoperative risk for
      complications should be facilitated by using intraoperative digital volume
      tomography-assisted navigation and intraoperative digital volume tomography
      control of electrode position. The results after CI surgery vary due to the
      differing extent of additional disabilities such as developmental delay,
      intellectual delay, and visual impairment. Nine of our patients showed improved
      responsiveness with the cochlear implant. Open speech comprehension could not be
      observed in 8 patients, whereas the follow-up period was less than 1 year in 4
      patients. The relatively high age of our patients at implantation might be an
      important factor. CONCLUSION: Careful planning of the treatment of CHARGE
      syndrome patients with sensorineural hearing loss can, to a limited extent, lead
      to auditory benefit without increasing surgical complications. Cochlear
      implantation is therefore indicated after critical assessment.

PMID- 19841602
TI  - Posterior semicircular canal dehiscence: first reported case series.
AB  - OBJECTIVE: To identify clinical, audiological, and vestibular characteristics of
      posterior semicircular canal dehiscence. STUDY DESIGN: Retrospective case review.
      SETTING: Tertiary referral center. PATIENTS: Twelve patients aged 2 to 67 years
      identified with posterior semicircular canal dehiscence. INTERVENTIONS: Patients
      identified by suspicious clinical history and examination, confirmed by high
      resolution computed tomography. Audiological evaluation included air and bone
      audiometry, tympanometry, acoustic reflexes, and vestibular evoked myogenic
      potential testing. RESULTS: Hearing loss was mixed in 9 patients, conductive in 2
      patients, and sensorineural in 1 patient, with downward-sloping configuration
      being the most common. Imaging revealed that 7 of 12 patients had dehiscence into
      a high-riding jugular bulb and 1 patient had an enlarged vestibular aqueduct with
      a Mondini malformation. One patient had Apert syndrome and another patient had
      microtia/atresia. Vestibular symptoms were more common in the adult patients than
      in the pediatric patients, with chronic disequilibrium the most common complaint.
      Vestibular evoked myogenic potential testing confirmed dehiscence with the
      characteristic response of reduced threshold and higher amplitude compared with
      healthy patients. CONCLUSION: This is the first reported series of adult and
      pediatric patients with symptomatic posterior semicircular canal dehiscence.
      Posterior semicircular canal dehiscence represents a third-window lesion
      manifesting as hearing loss with vestibular dysfunction. Computed tomography
      findings of a dehiscent posterior canal can be verified with increased vestibular
      evoked myogenic potential responses as in other third-window lesions. Patients
      found to have a high-riding jugular bulb and hearing loss should have specific
      inspection of the posterior canal to ensure it is not dehiscent.

PMID- 19841603
TI  - Self-reported effects of Meniere's disease on the individual's life: a
      qualitative analysis.
AB  - OBJECTIVE: To define the main consequences of Meniere's disease as perceived by
      individuals with the condition. STUDY DESIGN AND SETTING: Open-ended
      questionnaire sent to a 1-in-6 sample of members of the Finnish Meniere's
      Association. PATIENTS: Two hundred members of the Finnish Meniere's Association
      reporting a diagnosis compatible with the condition. INTERVENTION(S): Postal
      questionnaire, including the question "Please make a list of the main effects
      that your Meniere's disorder has on your life." MAIN OUTCOME MEASURE(S): Number
      of respondents listing 1 or more consequences of their condition. Categories of
      responses listed and numbers of responses within the different categories as
      defined by World Health Organization-International Classification of Functioning,
      Disability and Health. RESULTS: There was a 79% response rate to the overall
      questionnaire, and 91% of the respondents listed 1 or more consequences of their
      Meniere's disease, with a mean of 3.4 consequences listed. These were divided
      according to the categories listed in International Classification of
      Functioning, Disability and Health. Seventy percent of the respondents listed
      impairments, 39% activity limitations, 47% participation restrictions, 16%
      effects on environmental factors, and 28% on personal contextual factors.
      Although most impairments covered the main symptoms of the condition, 19% of the
      respondents listed "mental effects." Mobility problems were reported by more than
      half of those listing activity limitations, with most of the remainder being
      "communication." The 2 main areas of participation restrictions commonly reported
      were "community, social and civic life" and "work and employment." CONCLUSION:
      Most individuals with Meniere's disease are able to specify important
      consequences (principally participation restrictions and activity limitations),
      many of which are not identified in symptom-orientated approaches.

PMID- 19841604
TI  - Melting muscles: novel H1N1 influenza A associated rhabdomyolysis.
AB  - We report the first case of myositis and rhabdomyolysis after infection with
      novel influenza A (H1N1/09) virus. The case demonstrates the novel virus'
      capacity for causing significant disease. Myositis and the possibility of
      rhabdomyolysis should be considered in any individual presenting with influenza
      like symptoms in which severe myalgia or muscle weakness is apparent. It is
      likely that we will see severe clinical manifestations of infection with this
      novel influenza virus in the coming respiratory virus season.

PMID- 19841605
TI  - Impact of routine hepatitis B immunization on the prevalence of chronic hepatitis
      B virus infection in the marshall islands and the federated States of micronesia.
AB  - BACKGROUND: To evaluate the impact of routine hepatitis B (HB) vaccination on the
      prevalence of chronic hepatitis B virus (HBV) infection among children in Pacific
      Island countries where HBV infection was highly endemic, we conducted HB
      serosurveys during 2000 to 2007 among women of childbearing age born before
      implementation of HB vaccination and among children born after its
      implementation. METHODS: Serum specimens were collected from children aged 2 to 6
      years and their mothers in Chuuk, Federated States of Micronesia in 2000,
      children aged 2 to 9 years and their mothers in Pohnpei, Federated States of
      Micronesia in 2005, and 5- to 9-year-old children and prenatal clinic patients in
      2007 in Republic of the Marshall Islands (RMI). Specimens were tested for HB
      surface antigen (HBsAg) and antibodies to HB core antigen (total anti-HBc). HB
      vaccination coverage was determined from health department vaccination
      registries. We defined chronic HBV infection as the presence of HBsAg. RESULTS:
      Birthdose and 3 dose HB vaccination coverage was 48% and 87%, respectively, in
      Chuuk, 87% and 90% in Pohnpei, and 49% and 93% in RMI. Chronic HBV infection
      prevalence among children was 2.5% (9/362) in Chuuk, 1.5% (7/478) in Pohnpei and
      1.8% (6/331) in RMI. Chronic HBV infection prevalence among women was 9.2%
      (21/229) in Chuuk, 4.4% (10/229) in Pohnpei, and 9.5% (11/116) in RMI.
      CONCLUSIONS: Hepatitis B vaccination has resulted in a substantial decline in
      chronic infection in children in the Pacific Islands. HB vaccine effectiveness is
      high in this region, despite challenges in providing HB vaccine at birth and
      completing vaccination series on schedule.

PMID- 19841606
TI  - Nosocomial rotavirus gastroenteritis in Spain: a multicenter prospective study.
AB  - BACKGROUND: The objective of this study was to assess the incidence of nosocomial
      rotavirus gastroenteritis among children <2 years of age. METHODS: We conducted a
      prospective active surveillance for acute gastroenteritis (AGE) in the pediatric
      wards of 3 representative hospitals in Valencia (Spain) from October 2006 to
      March 2007, among children between 1 and 23 months of age with acute diarrhea.
      Children were followed up for 3 days after discharge. We obtained clinical and
      demographic information from participants and tested their stool specimens for
      rotavirus. RESULTS: A total of 1576 children were hospitalized at the 3 hospitals
      and 1300 (82.5%) were followed up as the study cohort. In 69 children, AGE
      started 48 hours after admission and were considered nosocomial infections. In 35
      of the 59 cases where stool samples were obtained, rotavirus (RV) was present
      (59%), and in 12 of them symptoms started after discharge. The accumulated
      incidence of nosocomial rotavirus disease during the study period was 2.8 cases
      per 100 inpatients (95% CI: 1.9-3.8), and the incidence rate was 4.8 cases per
      1000 hospital days (95% CI: 3.2-6.5). The most commonly found genotype in
      nosocomial infection was G9P[8], in 23 cases (66%), followed by G1P[8] in 4 cases
      (11%). The total economic cost was 883 euro per case. CONCLUSION: Active
      surveillance demonstrated that the burden of nosocomial rotavirus disease is
      substantial, and G9P [8] was the genotype found most frequently. Following up
      children after discharge from hospital allowed the discovery of cases of
      nosocomial RVAGE which are missed in most other studies.

PMID- 19841607
TI  - Effectiveness of varicella vaccines as postexposure prophylaxis.
AB  - BACKGROUND: Although chickenpox is usually a mild disease, it is not always free
      of complications, especially in adolescents and adults. Previous studies of
      postexposure prophylaxis conducted with experimental vaccines showed the vaccine
      to be highly effective if administered in the first 3 to 5 days after exposure.
      However, studies carried out with commercialized vaccines yielded discordant
      results. The aim of the present study was to assess the effectiveness of
      currently available varicella vaccines as postexposure prophylaxis. METHODS: We
      conducted a prospective cohort study. Patients susceptible to chickenpox
      consulting at the Preventive Medicine Department of the Vall d'Hebron Hospital
      after household exposure to a case of chickenpox were included. Postexposure
      prophylaxis with varicella vaccine was administered within the first 5 days after
      contact. Subjects were interviewed by telephone between 4 and 8 weeks after
      vaccination to ascertain whether chickenpox had appeared and, if so, its
      severity. The effectiveness of the vaccine in preventing and attenuating the
      disease was calculated with a confidence interval of 95%. RESULTS: Sixty-seven
      subjects were included in the study. Effectiveness of the varicella vaccine in
      preventing any type of disease was 62.3% (CI 95%: 47.8-74.9) and 79.4% (CI 95%:
      66.4-88.9) in preventing moderate and severe disease. No statistically
      significant differences were found when effectiveness was compared according to
      sex, age, or days elapsed since exposure. CONCLUSIONS: Administration of
      varicella vaccines within the first 5 days postexposure is effective in
      preventing chickenpox and in attenuating the illness.

PMID- 19841608
TI  - Alternative dosage of zidovudine in infants exposed to maternal human
      immunodeficiency virus infection.
AB  - As part of the 076 protocol, ZDV was given to HIV-exposed neonates for the first
      6 weeks of life. The dosage was 2 mg/kg every 6 hours. Frequent dosing can be a
      deterrent to regimen adherence. We report our experience, using 3 mg/kg every 8
      hours in 155 eligible HIV-exposed neonates, none of whom became HIV infected.
      Maximum risk of transmission that could be missed by this cohort is approximately
      2%, which is consonant with current transmission rates. ZDV at 3 mg/kg every 8
      hours is noninferior to 2 mg/kg every 6 hours and easier to administer.

PMID- 19841609
TI  - Pharmacogenetic association study of 30 genes with phenobarbital drug response in
      epileptic dogs.
AB  - BACKGROUND: Epilepsy, with a prevalence as high as 6%, is the most common
      neurological disorder in dogs. Although several antiepileptic drugs are in common
      use, in one-third of all epileptic dogs, adequate seizure control is not achieved
      with a single medication, and hence a combinatorial drug treatment must be
      adopted. Exploration of the genetic mechanisms involved in drug response may
      provide better treatment options for epileptic patients. METHODS AND RESULTS: A
      custom Illumina BeadChip was designed for high throughput genotyping of 384
      single nucleotide polymorphisms in 30 genes involved in drug metabolism, drug
      targeting, and drug transport. A case-control association study of 125 epileptic
      dogs identified five genes with suggestive association to phenobarbital drug
      response: KCNQ3, P=0.0003; SNC2A2, P=0.0008; EPOX HYD, P=0.0005; ABCC4, P=0.0091;
      and GABRA2, P=0.0130. These associations are not significant after adjustment for
      multiple comparisons, but on functional grounds may tag strong candidate genes.
      The study was powered to detect alleles with at least 3.5-fold additive increases
      in responsiveness. A combined area under the curve value of 0.74 from receiver
      operating curve analysis also provides suggestive support for their consideration
      as canine pharmacogenetic markers. CONCLUSION: Further replication and assessment
      of breed specificity is required before these markers can be considered as
      predictive of responsiveness to phenobarbital in dogs.

PMID- 19841610
TI  - Differentiation of intervertebral notochordal cells through live automated cell
      imaging system in vitro.
AB  - STUDY DESIGN: We demonstrated the differentiation of notochordal cells by direct
      observation using a live automated cell imaging system. We also hypothesized that
      notochordal cells have characteristics of chondrocyte-like cells. OBJECTIVE: To
      determine characteristics of notochordal cells by matrix protein expression and
      their differentiation using a live automated cell imager. SUMMARY OF BACKGROUND
      DATA: Although notochordal cells are critical to homeostasis of intervertebral
      disc, their fate has not been extensively studied and there is little evidence of
      notochordal cells as progenitors. METHODS: Notochordal cells purified from rabbit
      nucleus pulposus were isolated after serial filtration. Notochordal cells in 3
      dimensional culture were compared to chondrocyte-like cells by S sulfate
      incorporation into proteoglycan and reverse transcription polymerase chain
      reaction for gene expression(collagen II and aggrecan). Notochordal cells in 2-D
      culture were used for immunocytochemical staining (collagen II, aggrecan, and
      SOX9) and time-lapsed cell tracking study. RESULTS: Notochordal cells were
      capable of proteoglycan production at a rate comparable to chondrocyte-like cells
      (108% +/- 22.6% to chondrocyte-like cells) and expressed collagen II, aggrecan,
      and SOX9. In time-lapsed cell tracking analysis, notochordal cells were slower in
      population doubling time than chondrocyte-like cells and differentiated into 3
      morphologically distinct cell types: vacuolated cells (area: 2392 +/- 507.1
      microm, velocity: 0.09 +/- 0.01 microm/min); giant cells (area: 12678 +/- 1637.0
      microm, velocity: 0.08 +/- 0.01 microm/min) which grew rapidly without cell
      division; polygonal cells (area: 3053 +/- 751.2 microm, 0.14 +/- 0.01 microm/min)
      morphologically similar to typical differentiation type of chondrocyte-like cells
      (area: 2671 +/- 235.6 microm, 0.19 +/- 0.01 microm/min). Rarely, notochordal
      cells formed clusters analogous to that observed in vivo. CONCLUSION: These
      studies demonstrate a chondrocyte phenotype of notochordal cells and are the
      first direct evidence of notochordal cell differentiation, suggesting that they
      may act as progenitor cells, which has the potential to lead to their use in
      novel approaches to regeneration of degenerative intervertebral disc.

PMID- 19841611
TI  - Dynamic bulging of intervertebral discs in the degenerative lumbar spine.
AB  - STUDY DESIGN: The effect of postural change on degenerative lumbar discs was
      quantified using novel kinematic magnetic resonance imaging (kMRI). OBJECTIVE:
      The purpose is to describe the bulging of degenerative intervertebral lumbar
      discs in vivo subjected to different postural loads using a novel kMRI. SUMMARY
      OF BACKGROUND DATA: Symptomatic lumbar disc degeneration is a leading cause of
      pain and disability throughout the world. Over 70% of US citizens will experience
      a debilitating episode of low back pain. Earlier reports of degenerative disc
      changes are cadaver studies or are performed with recumbent MRI that eliminates
      the functional effects of gravity and muscle power. Little data are available on
      the behavior of degenerative intervertebral discs in vivo under physiologic
      loads. METHODS: A total of 513 patients obtained kMRI. Disc bulging beyond the
      intervertebral space was quantified during upright neutral, flexion, and
      extension imaging. The degree of intervertebral disc degeneration was correlated
      using the Pfirrmann Classification. RESULTS: Moderately degenerated
      intervertebral discs (grade III and IV) demonstrated greater bulging than mildly
      degenerated discs (grade II). Severely degenerated discs (grade V) also showed a
      trend toward greater bulging, but this was not significant. Grade I discs at all
      levels moved posteriorly in flexion and anteriorly in extension when compared to
      neutral posture. However, mild to severe (grade II-V) degenerative discs behaved
      differently in response to postural loads. Extension resulted in significant
      posterior bulging, while flexion did not demonstrate obvious anterior
      derangement. CONCLUSION: Disc bulging increases with the severity of disc
      degeneration. Grade I discs demonstrate the expected sagittal migration in
      response to postural load. However, more degenerative discs behave less
      predictably, and spine extension may result in significant posterior disc
      bulging. Degenerative changes in the intervertebral disc significantly affect the
      kinematic patterns under postural load in vivo. kMRI is a useful tool to quantify
      the kinematic behavior of degenerative intervertertebral discs.

PMID- 19841612
TI  - Quality of low back pain guidelines improved.
AB  - STUDY DESIGN: Systematic review of clinical guidelines. OBJECTIVE: To assess the
      methodological quality of clinical guidelines for the management of acute and
      chronic low back pain (LBP) in primary care and compare their recommendations.
      SUMMARY OF BACKGROUND DATA: A guideline evaluation performed in 2004 concluded
      that the quality and transparency of the development process and consistency in
      the reporting of primary care guidelines for LBP need to be improved. At present,
      several guidelines have been revised and new guidelines are published. We
      evaluated if the quality of guidelines has improved. METHODS: Guidelines
      published since 2004 were selected by electronically searching in MEDLINE,
      Cochrane Back Review Group database, Guideline Clearing House, Google, and
      contacting experts. The methodological quality of the guidelines was assessed by
      2 authors independently, using the Appraisal of Guidelines, Research, and
      Evaluation in Europe instrument. Also, the diagnostic and therapeutic
      recommendations were compared. RESULTS: Fourteen guidelines were included. In
      general, the quality was satisfactory. The guidelines had best scores on clarity
      and presentation. The domain scores of scope and purpose were often moderate due
      to the absence of description of the clinical questions. The domain of
      stakeholder involvement scored moderate, mostly because guidelines were not
      tested among target users. Domains that had generally low scores were
      applicability and editorial independence. Four guidelines scored low on the rigor
      of development, but the other guidelines scored high on this domain.The
      diagnostic and therapeutic recommendations in the guidelines for acute LBP were
      mainly comparable while the recommendations for the management of chronic LBP
      varied widely. CONCLUSION: Compared to the quality assessment performed in 2004,
      the average quality of guidelines has improved. However, guideline developers
      should still improve the quality transparency of the development process.
      Especially the applicability of guidelines and the editorial independence need to
      be ensured in future guidelines.

PMID- 19841613
TI  - Lumbar segmental mobility according to the grade of the disc, the facet joint,
      the muscle, and the ligament pathology by using kinetic magnetic resonance
      imaging.
AB  - STUDY DESIGN: The kinematic study of human lumbar spinal movements. OBJECTIVE: To
      investigate how disc degeneration and the degeneration of facet joint, ligaments,
      and paraspinal muscles are associated with lumbar segmental mobility. SUMMARY OF
      BACKGROUND DATA: Previous studies revealed relationship between spinal motion and
      osteoarthritic changes of facet joint as well as disc degeneration; however,
      little is known about the association of disc, facet joint, ligament, and muscle
      degeneration with lumbar segmental motion characteristics. METHODS: The 1580
      lumbar motion segments from 316 patients (200 male, 116 female) underwent Kinetic
      magnetic resonance imaging, which were used to assess disc degeneration (grade I
      V) and facet joint degeneration (grade 1-4), interspinous ligament (ISL)
      degeneration (grade 1-4), ligamentum flavum hypertrophy (LFH), and fatty
      degeneration of muscles. Segmental translational and angular motion in the
      flexion, extension, and neutral postures were digitally automatically measured by
      MR analyzer. RESULTS: Grade II (46.77%) disc, grade 1 (48.35%) facet joint
      degeneration, and grade 1 (64.1%) ISL were most common. LFH was most common in L4
      L5 (49/330, 14.8%). In younger age (<35), grade I disc and grade 1 facet joint
      were predominant compared with the older age (35< or = and <45) in which grade
      III, IV, and V disc and grade 2 facet joint were predominant (P < 0.05).
      Translational motion increased significantly in high grade of disc and facet
      joint (except grade V disc and grade 4 facet joint) and with LFH in L1-L5 (P <
      0.05). Angular motion significantly decreased in grade V disc, grade 4 ISL, and
      without LFH in L1-L5 (P < 0.05). According to muscle fatty degeneration,
      translational and angular motions were not significantly changed. CONCLUSION: Our
      results support that facet joint degeneration is followed by disc degeneration
      according to age. Increased translational movements of the lumbar segments
      occurred in severe disc degeneration accompanied by facet joint degeneration or
      the presence of LFH even if the movements were stabilized in the advanced status.
      Therefore, the current status of the intervertebral discs, facet joints, and
      ligamentum flavum should be taken into consideration when evaluating stability
      within the lumbar spine.

PMID- 19841614
TI  - [Polish guidelines for the prevention and treatment of venous thromboembolism:
      2009 update].
AB  - The overall objective of the Polish guidelines for the prevention and treatment
      of venous thromboembolism is to increase patient benefit and safety by
      appropriate prevention and treatment of deep vein thrombosis and pulmonary
      embolism as well as proper management of the complications associated with
      antithrombotic and thrombolytic therapy. These guidelines apply to adult trauma,
      cancer, surgical, and medical patients as well as those at increased risk of
      venous thromboembolism. Specific recommendations have been formulated for
      pregnant women, patients requiring surgery while receiving long-term oral
      anticoagulant treatment, and patients undergoing regional anesthesia and/or
      analgesia. We systematically identified all current clinical practice guidelines
      concerning the prevention and/or treatment of venous thromboembolism and assessed
      their methodological quality using the AGREE instrument. We chose to update
      existing Polish guidelines by adapting the most recent high quality guidelines
      that we identified to Polish cultural and organizational setting rather than
      develop all recommendations de novo. We based our recommendations primarily on
      the 8th edition of the American College of Chest Physicians (ACCP) Evidence-Based
      Clinical Practice Guidelines on Antithrombotic and Thrombolytic Therapy and on
      the European Society of Cardiology (ESC) Guidelines on the Diagnosis and
      Management of Acute Pulmonary Embolism. To make recommendations regarding
      specific management issues that had not been addressed in ACCP guidelines, or
      whenever panel members felt they needed additional information to reach the
      decision we also consulted guidelines developed by other professional societies
      and organizations as well as additional sources of evidence. For each
      recommendation we explicitly assessed its relevance and applicability in the
      context of health care system in Poland. We adapted recommendations when
      necessary, explicitly stating the rationale for modification and judgements about
      the values and preferences we assumed. We developed original recommendations on
      the use of new oral anticoagulants that have recently become available, following
      the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
      approach.

PMID- 19841615
TI  - DNA transfection of mammalian skeletal muscles using in vivo electroporation.
AB  - A growing interest in cell biology is to express transgenically modified forms of
      essential proteins (e.g. fluorescently tagged constructs and/or mutant variants)
      in order to investigate their endogenous distribution and functional relevance.
      An interesting approach that has been implemented to fulfill this objective in
      fully differentiated cells is the in vivo transfection of plasmids by various
      methods into specific tissues such as liver, skeletal muscle, and even the brain.
      We present here a detailed description of the steps that must be followed in
      order to efficiently transfect genetic material into fibers of the flexor
      digitorum brevis (FDB) and interosseus (IO) muscles of adult mice using an in
      vivo electroporation approach. The experimental parameters have been optimized so
      as to maximize the number of muscle fibers transfected while minimizing tissue
      damages that may impair the quality and quantity of the proteins expressed in
      individual fibers. We have verified that the implementation of the methodology
      described in this paper results in a high yield of soluble proteins, i.e. EGFP
      and ECFP, calpain, FKBP12, beta2a-DHPR, etc. ; structural proteins, i.e.
      minidystrophin and alpha-actinin; and membrane proteins, i.e. alpha1s-DHPR, RyR1,
      cardiac Na/Ca(2+) exchanger , NaV1.4 Na channel, SERCA1, etc., when applied to
      FDB, IO and other muscles of mice and rats. The efficient expression of some of
      these proteins has been verified with biochemical and functional evidence.
      However, by far the most common confirmatory approach used by us are standard
      fluorescent microscopy and 2-photon laser scanning microscopy (TPLSM), which
      permit to identify not only the overall expression, but also the detailed
      intracellular localization, of fluorescently tagged protein constructs. The
      method could be equally used to transfect plasmids encoding for the expression of
      proteins of physiological relevance (as shown here), or for interference RNA
      (siRNA) aiming to suppress the expression of normally expressed proteins (not
      tested by us yet). It should be noted that the transfection of FDB and IO muscle
      fibers is particularly relevant for the investigation of mammalian muscle
      physiology since fibers enzymatically dissociated from these muscles are
      currently one of the most suitable models to investigate basic mechanisms of
      excitability and excitation-contraction coupling under current or voltage clamp
      conditions.

PMID- 19841616
TI  - Curcumin attenuates the effects of insulin on stimulating hepatic stellate cell
      activation by interrupting insulin signaling and attenuating oxidative stress.
AB  - Hyperinsulinemia associated with type II diabetes mellitus (T2DM) is a risk
      factor for non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. Hepatic
      stellate cells (HSCs) are the major effectors in collagen production during
      hepatic fibrogenesis. Elevated levels of insulin stimulate HSC activation. In
      addition to its anti-diabetic effects, the antioxidant curcumin, the yellow
      pigment in curry from turmeric, suppresses HSC activation and protects the liver
      from fibrogenesis in vitro and in vivo. This study aims at evaluating the effect
      of curcumin on insulin-induced HSC activation and further elucidating the
      underlying mechanisms. We report that curcumin dose-dependently eliminates
      insulin-induced HSC activation by suppressing expression of type I collagen gene
      and other key genes relevant to HSC activation. Additional experiments indicate
      that curcumin interrupts insulin signaling in HSCs by reducing the
      phosphorylation level of insulin receptor (InsR) and suppressing gene expression
      of InsR. Furthermore, curcumin attenuates insulin-induced oxidative stress in
      HSCs by inducing gene expression of glutamate-cysteine ligase (GCL), leading to
      de novo synthesis of glutathione and the suppression of gene expression of InsR.
      These results support our initial hypothesis that curcumin inhibits the effects
      of insulin on stimulating HSC activation by interrupting insulin signaling and
      attenuating oxidative stress. Our results provide novel insights into the
      mechanisms by which curcumin inhibits the insulin-induced HSC activation.

PMID- 19841617
TI  - Acyclic retinoid inhibits angiogenesis by suppressing the MAPK pathway.
AB  - Acyclic retinoid (ACR) is currently under clinical trial as an agent to suppress
      the recurrence of hepatocellular carcinoma (HCC) through its ability to induce
      apoptosis in premature HCC cells. ACR has an anticancer effect in vivo as well,
      although it shows weak apoptosis-inducing activity against mature HCC cells,
      suggesting the existence of an additional action mechanism. In this study, we
      investigated the antiangiogenic activity of ACR. ACR inhibited angiogenesis
      within chicken chorioallantoic membrane (CAM) in as similar a manner as all-trans
      retinoic acid (atRA). Although suppression of angiogenesis by atRA was partially
      rescued by the simultaneous addition of angiopoietin-1, suppression of
      angiogenesis by ACR was not rescued under the same condition at all. Conversely,
      although suppression of angiogenesis by ACR was partially inverted by the
      simultaneous addition of vascular endothelial growth factor (VEGF), suppression
      of angiogenesis by atRA was not affected under the same condition. These results
      suggested that mechanisms underlying the suppression of angiogenesis by ACR and
      atRA were different. ACR selectively inhibited the phosphorylation of VEGF
      receptor 2 (VEGFR2) and of extracellular signal-regulated kinase (ERK) without
      changing their protein expression levels, and inhibited endothelial cell growth,
      migration, and tube formation. The inhibition of the phosphorylation of ERK,
      endothelial growth, migration, tube formation, and angiogenesis by ACR was
      rescued by the overexpression of constitutively active mitogen-activated protein
      kinase (MAPK). Finally, ACR, but not atRA, inhibited HCC-induced angiogenesis in
      a xenografted CAM model. These results delineate the novel activity of ACR as an
      antiangiogenic through a strong inhibition of the VEGFR2 MAPK pathway.

PMID- 19841618
TI  - Foxl1 promotes liver repair following cholestatic injury in mice.
AB  - Cholangiocyte proliferation is one of the hallmarks of the response to
      cholestatic injury. We previously reported that the winged helix transcription
      factor Foxl1 is dramatically induced in cholangiocytes following bile duct
      ligation. In this study, we investigated the function of Foxl1 in the bile duct
      ligation model of cholestatic liver injury in Foxl1(-/-) and control mice. We
      found that Foxl1(-/-) livers exhibit an increase in parenchymal necrosis,
      significantly impaired cholangiocyte and hepatocyte proliferation, and failure to
      expand bile ductular mass. Wnt3a and Wnt7b expression was decreased in the livers
      of Foxl1(-/-) mice along with reduced expression of the beta-catenin target gene
      Cyclin D1 in Foxl1(-/-) cholangiocytes. These results show that Foxl1 promotes
      liver repair after bile-duct-ligation-induced liver injury through activation of
      the canonical wnt/beta-catenin pathway.

PMID- 19841621
TI  - Eyes wide open.

PMID- 19841619
TI  - Identification of a bone marrow-derived mesenchymal progenitor cell subset that
      can contribute to the gastric epithelium.
AB  - Recent studies with Helicobacter-infected mice have shown that bone marrow
      derived cells can repopulate the gastric epithelium and progress to cancer.
      However, it has not been established which cellular subset can potentially
      contribute to the epithelium. The aim of this study was to investigate the
      ability of bone marrow-derived mesenchymal stem cells (MSCs) that express
      cytokeratin 19 (K19) to contribute to the gastric epithelium. MSCs cultures were
      established from whole bone marrow and expression of K19 was detected in a
      minority (1 of 13) of clones by real-time PCR and immunostaining. Transfection of
      a K19-green fluorescent protein (GFP) vector and isolation of GFP-expressing
      colonies generated high K19-expressing MSC clones (K19GFPMSC). Incubation of MSCs
      with gastric tissue extract markedly induced mRNA expression of gastric
      phenotypic markers and was observed to a greater extent in K19GFPMSCs compared
      with parental MSCs and mock transfectants. Both K19GFPMSCs and GFP-labeled
      control MSCs gave rise to gastric epithelial cells after injection into the
      murine stomach. In addition, after blastocyst injections, K19GFPMSCs gave rise to
      GFP-positive gastric epithelial cells in all 13 pups, whereas only 3 of 10
      offspring showed GFP-positive gastric epithelial cells after injection of GFP
      labeled control MSCs. Although K19 expression could not be detected in murine
      whole bone marrow, H. felis infection increased K19-expressing MSCs in the
      circulation. Taken together, our results show that bone marrow-derived MSCs can
      contribute to the gastric epithelium. The K19-positive MSC fraction that is
      induced by chronic H. felis infection appears to be the important subset in this
      process.

PMID- 19841622
TI  - Post-reductionist protein science, or putting Humpty Dumpty back together again.

PMID- 19841623
TI  - The nanny model for IDPs.

PMID- 19841624
TI  - Locking out viral replication.

PMID- 19841625
TI  - The physical chemistry of membrane curvature.

PMID- 19841626
TI  - Slow growth leads to a switch.

PMID- 19841628
TI  - The role of dynamic conformational ensembles in biomolecular recognition.
AB  - Molecular recognition is central to all biological processes. For the past 50
      years, Koshland's 'induced fit' hypothesis has been the textbook explanation for
      molecular recognition events. However, recent experimental evidence supports an
      alternative mechanism. 'Conformational selection' postulates that all protein
      conformations pre-exist, and the ligand selects the most favored conformation.
      Following binding the ensemble undergoes a population shift, redistributing the
      conformational states. Both conformational selection and induced fit appear to
      play roles. Following binding by a primary conformational selection event,
      optimization of side chain and backbone interactions is likely to proceed by an
      induced fit mechanism. Conformational selection has been observed for protein
      ligand, protein-protein, protein-DNA, protein-RNA and RNA-ligand interactions.
      These data support a new molecular recognition paradigm for processes as diverse
      as signaling, catalysis, gene regulation and protein aggregation in disease,
      which has the potential to significantly impact our views and strategies in drug
      design, biomolecular engineering and molecular evolution.

PMID- 19841629
TI  - Computer-aided design of functional protein interactions.
AB  - Predictive methods for the computational design of proteins search for amino acid
      sequences adopting desired structures that perform specific functions. Typically,
      design of 'function' is formulated as engineering new and altered binding
      activities into proteins. Progress in the design of functional protein-protein
      interactions is directed toward engineering proteins to precisely control
      biological processes by specifically recognizing desired interaction partners
      while avoiding competitors. The field is aiming for strategies to harness recent
      advances in high-resolution computational modeling-particularly those exploiting
      protein conformational variability-to engineer new functions and incorporate many
      functional requirements simultaneously.

PMID- 19841632
TI  - Neuroculture.
AB  - Neuroscience addresses questions that, if resolved, will reveal aspects of our
      individuality. Therefore neuroscientific knowledge is not solely constrained
      within laboratories, but readily captures the attention of the public at large.
      Ideas, concepts and images in neuroscience widely circulate in culture and are
      portrayed in literature, film, works of art, the mass media and commercial
      products, therefore shaping social values and consumer practices. The interaction
      between art and science offers an opportunity to make the scientific community
      and the public aware of the social and ethical implications of the scientific
      advances in neuroscience.

PMID- 19841630
TI  - NMR spectroscopy brings invisible protein states into focus.
AB  - Molecular dynamics are essential for protein function. In some cases these
      dynamics involve the interconversion between ground state, highly populated
      conformers and less populated higher energy structures ('excited states') that
      play critical roles in biochemical processes. Here we describe recent advances in
      NMR spectroscopy methods that enable studies of these otherwise invisible excited
      states at an atomic level and that help elucidate their important relation to
      function. We discuss a range of examples from molecular recognition, ligand
      binding, enzyme catalysis and protein folding that illustrate the role that
      motion plays in 'funneling' conformers along preferred pathways that facilitate
      their biological function.

PMID- 19841634
TI  - Influence of physical exercise on quality of life in individuals with spinal cord
      injury.
AB  - STUDY DESIGN: Retrospective cross-sectional study with anonymous postal data
      collection. OBJECTIVE: Regaining the best possible mobility and independence is
      not only the focus of the rehabilitation process for individuals with spinal cord
      injury (SCI), but also represents an important criterion for the individual's
      quality of life (QoL). Therefore, if and to what extent physical exercise (PE)
      influences the QoL of individuals with SCI was investigated. SETTING: The period
      of investigation extended from September 2007 to January 2008. Data were acquired
      from the BG Trauma Hospital Hamburg database and the German Wheelchair Sport
      Federation databases. METHODS: Analysis of 277 questionnaires of individuals with
      acquired SCI between the age of 16 and 65 years with complete wheelchair
      dependency in everyday life and lesion level lower C5. RESULTS: In all, 51.5% of
      all individuals were reported being actively involved in sports as opposed to
      48.5% individuals not participating in sports. Individuals actively involved in
      sports have higher employment rate than physically inactive individuals with SCI.
      PE was identified as the main influencing determinant of QoL. This was
      particularly within the physical and psychological dimensions. CONCLUSION: In
      discovering the potential of individuals with SCI for getting involved in PE, the
      improvement of physical and coordinative skills with interaction between
      individuals with SCI and external sport groups should be an inherent part of the
      rehabilitation process. Individuals not having access to PE should be given the
      opportunity to participate in wheelchair mobility courses. This may improve the
      adherence to PE of individuals with SCI in post-clinical settings.

PMID- 19841631
TI  - Targeting proteins for degradation.
AB  - Protein degradation plays a central role in many cellular functions. Misfolded
      and damaged proteins are removed from the cell to avoid toxicity. The
      concentrations of regulatory proteins are adjusted by degradation at the
      appropriate time. Both foreign and native proteins are digested into small
      peptides as part of the adaptive immune response. In eukaryotic cells, an ATP
      dependent protease called the proteasome is responsible for much of this
      proteolysis. Proteins are targeted for proteasomal degradation by a two-part
      degron, which consists of a proteasome binding signal and a degradation
      initiation site. Here we describe how both components contribute to the
      specificity of degradation.

PMID- 19841635
TI  - Developing a contemporary functional outcome measure for spinal cord injury
      research.
AB  - STUDY DESIGN: This study used qualitative analysis of focus group discussions.
      OBJECTIVE: The primary objective was to select functional activities to include
      in an item pool, which is the first step in developing a spinal cord injury
      computer adaptive test (SCI-CAT). SETTING: This multisite study was conducted at
      six US National Spinal Cord Injury Model Systems Programs. METHODS: Focus group
      discussions, which included persons with tetraplegia and paraplegia and
      clinicians, were conducted. Transcripts were analyzed using a grounded theory
      approach. Functional activities were identified, binned, winnowed, written as
      functional items, and cognitively tested. RESULTS: Focus group discussion
      analysis identified 326 functional activity items that fit into categories
      outlined in the International Classification of Functioning, Disability and
      Health (ICF) framework: Mobility (193 items), including assessment of functioning
      in a manual (44 items) and power wheelchair (19 items); self-care (109 items);
      and communication (19 items). Items related to sexual function were also
      identified (5 items). CONCLUSION: The SCI-CAT item pool includes items that
      assess functional activities important to persons with SCI. Items cover a wide
      range of functional ability and reflect most ICF categories. The SCI-CAT pool is
      currently being field tested to develop a calibrated item bank. Further
      development will yield a CAT of functional activities appropriate for SCI
      research.

PMID- 19841636
TI  - The relationship between bladder management and health-related quality of life in
      patients with spinal cord injury in the UK.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: (1) To assess the relationship
      between bladder management methods and the health-related quality of life (HRQL)
      in patients with spinal cord injury (SCI). (2) To identify any correlation
      between the two questionnaires used to assess the quality of life (one validated
      for SCI and one validated for bladder symptoms). SETTING: Spinal Cord Injury
      Centre, Royal National Orthopaedic Hospital, Middlesex, UK. METHODS: This study
      is based on two questionnaires with results collected from 142 people with SCI.
      The two questionnaires were based on information from the Short-Form 36-Item
      Health Survey (SF-36) and the King's Health Questionnaire and included
      demographic characteristics, bladder management methods and the frequency of
      incontinence. RESULTS: There is a moderate correlation between the results of the
      SF-36 and the King's Health Questionnaire. Only 21% SCI patients report normal
      voiding without any other form of bladder management. The type of bladder
      management may influence the HRQL in patients with SCI. Clean intermittent
      catheterization by attendant, indwelling transurethral catheterization and
      indwelling suprapubic catheterization are the three groups with the worst mental
      status. In addition, the frequency of incontinence is a strong influence on HRQL.
      CONCLUSIONS: The results of this study may provide a general baseline HRQL for
      patients with SCI. Our findings show the relationships between bladder management
      methods and quality of life in patients with SCI. In addition, the impact of
      incontinence on quality of life was also confirmed.

PMID- 19841637
TI  - The role of redox-dependent mechanisms in the downregulation of ligand-induced
      Toll-like receptors 7, 8 and 4-mediated HIF-1 alpha prolyl hydroxylation.
AB  - Toll-like receptors (TLRs) are key components of the innate immune system that
      allow immune cells to specifically detect pathogens by recognizing their specific
      molecular patterns. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is known to
      have a critical role in TLR downstream signalling by promoting energy metabolism,
      expression of proinflammatory cytokines and proangiogenic factors. However, the
      molecular mechanisms leading to the accumulation of HIF-1 alpha are not fully
      understood. In this study, we report that R848 (specific ligand)-induced
      activation of endosomal TLRs 7 and 8 (which recognize viral single-stranded RNA)
      and lipopolysaccharide (LPS)-induced activation of TLR4 (which specifically
      recognizes LPS as a ligand) leads to downregulation of degradative HIF-1 alpha
      prolyl hydroxylation. In the case of TLR7/8, this downregulation is achieved
      through redox- and reactive nitrogen species (RNS)-dependent mechanisms. S
      nitrosation of HIF-1 alpha protein was also observed. In the case of LPS-induced
      TLR4 activation, only a redox-dependent mechanism is involved. RNS and p38 MAP
      kinase (known to contribute to LPS-induced TLR4-dependent accumulation of HIF-1
      alpha protein) do not affect HIF-1 alpha prolyl hydroxylation. In both cases,
      downregulation of HIF-1 alpha prolyl hydroxylation correlates with a decrease in
      intracellular iron (II).

PMID- 19841638
TI  - HIF-dependent induction of adenosine receptor A2b skews human dendritic cells to
      a Th2-stimulating phenotype under hypoxia.
AB  - Hypoxia is a common characteristic of many pathological and physiological
      conditions that can markedly change cellular metabolism and cause the
      accumulation of extracellular adenosine. Recent studies have shown that adenosine
      can modulate the function of certain immune cell types through binding with
      different adenosine receptors. Our previous studies have shown that hypoxia has
      an effect on the biological activity of dendritic cells (DCs) by inducing their
      differentiation towards a Th2 polarising phenotype. However, the mechanisms
      underlying this suppression remain unclear. In this study, we have demonstrated
      that hypoxic mDCs predominantly express adenosine receptor A2b. The A2b receptor
      antagonist MRS1754 was able to increase the production of IL-12p70 and TNF-alpha
      by hypoxic mDCs and elevate the amount of Th1 cytokine IFN-gamma production in a
      mDCs-T-cell co-culture system. We also found that the effect of hypoxia on IL
      12p70 production was mediated via increased intracellular cAMP levels through the
      up-regulation of A2b adenosine receptor and the preferential expression of
      adenosine A2b receptors in hypoxic mDCs was HIF-1 alpha dependent. Therefore, the
      hypoxic mDCs could provide a useful tool for researching the function of A2bR in
      human DCs. Our results offer new insights into understanding the molecular
      mechanisms underlying the biological activities of DCs in local-tissue hypoxic
      microenvironments.

PMID- 19841639
TI  - Reverse signaling through BAFF differentially regulates the expression of
      inflammatory mediators and cytoskeletal movements in THP-1 cells.
AB  - Most members of the tumor-necrosis factor superfamily have been reported to
      mediate reverse signaling in T cells, macrophages, and/or dendritic cells. BAFF
      has been reported to have important functions in B-cell survival through forward
      signaling, but the presence of reverse signaling has not been explored. To
      investigate the possibility of BAFF-mediated reverse signaling, the expression
      patterns and functions of BAFF were analyzed in monocytic cell lines including
      the human macrophage-like cell line, THP-1. The expression of BAFF and its
      receptors was detected in monocytic cell lines, either before or after
      activation. The stimulation of BAFF induced the expression of matrix
      metalloproteinase (MMP)-9, interleukin -8, and transforming growth factor-beta
      induced gene product (beta ig-h3) and the upregulation of intercellular adhesion
      molecule-1 in THP-1 cells. The activation of mitogen-activated protein kinase
      extracellular signal-regulated kinase1/2 and nuclear factor-kappaB was required
      for these responses. In addition to these stimulatory effects, BAFF-mediated
      signaling inhibited processes involving cytoskeletal movement such as
      phagocytosis and transmigration through blocking the activation of
      phosphatidylinositol 3-kinase/AKT and Rac-1. Furthermore, murine primary
      macrophage culture such as peritoneal macrophages expressed BAFF and stimulation
      of it induced the expression of MMP-9. These observations show that the reverse
      signaling initiated from BAFF induces the expression of inflammatory mediators
      while suppressing the cytoskeletal movements associated with phagocytosis and
      transmigration.

PMID- 19841640
TI  - The 8th annual pharmacogenetics in psychiatry meeting report.

PMID- 19841641
TI  - Lessons learned.

PMID- 19841642
TI  - Navigating the leukocyte signaling maze guided by Ariadne's thread.
AB  - Ariadne is the legendary Minoan goddess of the Labyrinth. The term 'Ariadne's
      thread' is used to describe the understanding of complex issues. Immunologists
      attending the 5th Leukocyte Signal Transduction Workshop discussed the Ariadne's
      thread woven about intracellular signaling pathways.

PMID- 19841643
TI  - NDP52: the missing link between ubiquitinated bacteria and autophagy.
AB  - Mammalian cells ubiquitinate bacteria that erroneously enter the cytosol and
      target these intruding microbes for destruction by autophagy. New work shows that
      the protein NDP52 directly binds to ubiquitinated bacteria and facilitates the
      assembly of an autophagic membrane that surrounds these invaders.

PMID- 19841644
TI  - TLR2 joins the interferon gang.
AB  - The induction of type I interferon is a critical checkpoint in antiviral
      immunity. Toll-like receptor 2 can unexpectedly induce type I interferon in the
      subset of inflammatory monocytes during infection with vaccinia virus.

PMID- 19841645
TI  - The gut feeling of Treg cells: IL-10 is the silver lining during colitis.
AB  - Regulatory T cells that express the transcription factor Foxp3 are pivotal in
      suppressing autoimmune responses. A report in this issue describes a key role for
      interleukin 10 produced by lamina propria macrophages in maintaining Foxp3
      expression during inflammatory responses in the intestine.

PMID- 19841646
TI  - Positively selecting peptides: their job does not end in the thymus.
AB  - Peptides able to positively select major histocompatibility complex class II
      restricted thymocytes have not yet been defined. Two new reports identify and
      ascribe important extrathymic functions to several positively selecting peptides
      for CD4+ T cells.

PMID- 19841649
TI  - Statistical Aspects of the Use of Biomarkers in Nutritional Epidemiology
      Research.
AB  - Few strong and consistent associations have arisen from observational studies of
      dietary consumption in relation to chronic disease risk. Measurement error in
      self-reported dietary assessment may be obscuring many such associations.
      Attempts to correct for measurement error have mostly used a second self-report
      assessment in a subset of a study cohort to calibrate the self-report assessment
      used throughout the cohort, under the dubious assumption of uncorrelated
      measurement errors between the two assessments. The use, instead, of objective
      biomarkers of nutrient consumption to produce calibrated consumption estimates
      provides a promising approach to enhance study reliability. As summarized here,
      we have recently applied this nutrient biomarker approach to examine energy,
      protein, and percent of energy from protein, in relation to disease incidence in
      Women's Health Initiative cohorts, and find strong associations that are not
      evident without biomarker calibration. A major bottleneck for the broader use of
      a biomarker-calibration approach is the rather few nutrients for which a suitable
      biomarker has been developed. Some methodologic approaches to the development of
      additional pertinent biomarkers, including the possible use of a respiratory
      quotient from indirect calorimetry for macronutrient biomarker development, and
      the potential of human feeding studies for the evaluation of a range of urine-
      and blood-based potential biomarkers, will briefly be described.

PMID- 19841650
TI  - Antennal responses of an oligolectic bee and its cleptoparasite to plant
      volatiles.
AB  - Cleptoparasitic or cuckoo bees lay their eggs in nests of other bees, and the
      parasitic larvae feed the food that had been provided for the host larvae.
      Nothing is known about the specific signals used by the cuckoo bees for host nest
      finding, but previous studies have shown that olfactory cues originating from the
      host bee alone, or the host bee and the larval provision are essential. Here, I
      compared by using gas chromatography coupled to electroantennographic detection
      (GC-EAD) the antennal responses of the oligolectic oil-bee Macropis fulvipes and
      their cleptoparasite, Epeoloides coecutiens, to dynamic headspace scent samples
      of Lysimachia punctata, a pollen and oil host of Macropis. Both bee species
      respond to some scent compounds emitted by L. punctata, and two compounds, which
      were also found in scent samples collected from a Macropis nest entrance,
      elicited clear signals in the antennae of both species. These compounds may not
      only play a role for host plant detection by Macropis, but also for host nest
      detection by Epeoloides. I hypothesise that oligolectic bees and their
      cleptoparasites use the same compounds for host plant and host nest detection,
      respectively.

PMID- 19841648
TI  - A coming-of-age story: activation-induced cytidine deaminase turns 10.
AB  - The discovery and characterization of activation-induced cytidine deaminase (AID)
      10 years ago provided the basis for a mechanistic understanding of secondary
      antibody diversification and the subsequent generation and maintenance of
      cellular memory in B lymphocytes, which signified a major advance in the field of
      B cell immunology. Here we celebrate and review the triumphs in the mission to
      understand the mechanisms through which AID influences antibody diversification,
      as well as the implications of AID function on human physiology. We also take
      time to point out important ongoing controversies and outstanding questions in
      the field and highlight key experiments and techniques that hold the potential to
      elucidate the remaining mysteries surrounding this vital protein.

PMID- 19841651
TI  - Boron dependent membrane glycoproteins in symbiosome development and nodule
      organogenesis: A model for a common role of boron in organogenesis.
AB  - During the last two decades, we have analyzed the roles of boron (B) in the
      development of the legume-rhizobia symbiosis and nodule organogenesis. As in
      other plant tissues, B is needed for the maintenance of nodule cell wall
      structure. Moreover, several symbiotic events including rhizobial infection,
      nodule cell invasion and symbiosome development that involve membrane related
      functions (i.e., vesicle targeting, secretion, or cell surface interactions) are
      affected by B deficiency. Using anti-rhamnogalacturonan II (anti-RGII) antiserum
      and immunological techniques, we recently described membrane glycoproteins (RGII
      glycoproteins) developmentally regulated in Pisum sativum nodules, which are not
      detected by the antibody in B-deficient nodules. RGII-glycoproteins appeared
      related with development processes involving extensive membrane synthesis, like
      symbiosome maturation or cell growth, both of them negatively affected by B
      deficiency. Here, we suggest that, besides maintaining cell wall structure, B is
      both stabilizing components of the membrane glycocalyx and promoting interactions
      between cell surfaces glycoconjugates that are important during the establishment
      of the symbiosis and during nodule development. Moreover, we hypothesize that B
      is playing a similar role during plant or animal embryogenesis and development.

PMID- 19841652
TI  - Post-translational modifications mediated by reactive nitrogen species:
      Nitrosative stress responses or components of signal transduction pathways?
AB  - In animal cells, nitric oxide and NO-derived molecules have been shown to mediate
      post-translational modifications such as S-nitrosylation and protein tyrosine
      nitration which are associated with cell signalling and pathological processes,
      respectively. In plant cells, knowledge of the function of these post
      translational modifications under physiological and stress conditions is still
      very rudimentary. In this addendum, we briefly examine how reactive nitrogen
      species (RNS) can exert important effects on proteins that could mediate
      signalling processes in plants.

PMID- 19841653
TI  - 14-3-3 isoforms participate in red light signaling and photoperiodic flowering.
AB  - Members of the 14-3-3 family of proteins participate in signal transduction by
      modulating flux through various pathways. Potential subfunctionalization within
      this family has produced a suite of related proteins with diverse client
      interactions and discrete localization. The associated study assesses the
      biological roles of two specific 14-3-3 isoforms, using genetic, biochemical and
      physiological assays to ascertain potential nodes of interaction. Arabidopsis T
      DNA insertion mutants representing the nu and mu isoforms exhibited a short, yet
      clear delay in flowering time on long days. Tests of hypocotyl growth inhibition
      under narrow bandwidth light indicated a hyposensitivity to red light, while
      responses to blue and far-red light were normal. These physiological tests
      suggest a mechanistic link between 14-3-3 proteins, red light sensing, and the
      pathways that control photoperiodic flowering. The precise entry point into the
      pathway was assessed using yeast two hybrid assays targeted against specific
      proteins active in the circadian oscillator, light transduction and photoperiodic
      flowering. Yeast two hybrid interaction was observed with CONSTANS (CO), and then
      confirmed with coimmunoprecipitation. Functional interaction with phyB leading to
      defects in flowering time and direct interaction with CONSTANS circumstantially
      places these specific 14-3-3 isoforms into the pathway that regulates the
      transition between vegetative and floral development.

PMID- 19841654
TI  - GCR2 is a new member of the eukaryotic lanthionine synthetase component C-like
      protein family.
AB  - GCR2 was recently proposed to represent a G-protein-coupled receptor (GPCR) for
      the plant hormone, abscisic acid (ABA). We and others provided evidence that GCR2
      is unlikely to be a bona fide GPCR because it is not clearly predicted to contain
      seven transmembrane domains, a structural hallmark for classical GPCRs. Instead,
      GCR2 shows significant sequence similarity to homologs of bacterial lanthionine
      synthetase component C (LanC). Here, we provide additional analysis of GCR2 and
      LanC-like (LANCL) proteins in plants, and propose that GCR2 is a new member of
      the eukaryotic LANCL protein family.

PMID- 19841655
TI  - Specificity of induction responses in Sinapis alba L.: Plant growth and
      development.
AB  - Plant defenses are expected to be negatively correlated with plant growth,
      development and reproduction. In a recent study, we investigated the specificity
      of induction responses of chemical defenses in the Brassicaceae Sinapis alba.1 It
      was shown that glucosinolate levels and myrosinase activities increased to
      different degrees after 24-hours-feeding by a specialist or generalist herbivore
      or mechanical wounding. Here, we present the specific influences of these
      treatments on organ biomasses which were recorded as a measure of growth.
      Directly after the treatments, organ biomasses were reduced locally and
      systemically by herbivore feeding, but not by mechanical wounding compared to
      control plants. Induction of glucosinolates, which increased in all treatments,
      is thus not necessarily expressed as cost in terms of reduced growth in S. alba.
      No significant long-term differences in plant development between herbivore
      treated and control plants were found. Thus, tissue loss and increased
      investments in chemical defenses could be compensated over time, but compensation
      patterns depended on the inducing agent. Furthermore, herbivore treatments
      resulted in an increased mechanical defense, measured as abaxial trichome
      densities. Plants respond highly dynamic with regard to defense and growth
      allocation and due to different inductors.

PMID- 19841656
TI  - Harpins and ion channels modulations: Many ways to die.
AB  - Harpins are type three secretion system (TTSS) effectors. While few harpins are
      thought to be translocators of TTSS effectors through the host plasma membrane
      during plant/bacteria interactions, functions of many harpins remain for the
      moment mysterious. We recently showed that the HrpW(ea) harpin from Erwinia
      amylovora, at subnamolar concentration, was able to decrease defense responses
      triggered by another harpin from this bacteria, HrpN(ea). This antagonism could
      be the result of opposed anion channels modulations triggered by HrpW(ea) and
      HrpN(ea). At upper concentrations HrpW(ea) alone, or in combination with
      HrpN(ea), was able to induce cell death. This form of cell death involves strong
      ion channel activation and shares similarity with apoptosis volume decrease
      (AVD), a form of programmed cell death well described in animal cells. All these
      results suggest different ways for harpins to trigger cell death and highlight
      the role of ion channels during cell death processes.

PMID- 19841657
TI  - Apoplastic invertases: Multi-faced players in the arbuscular mycorrhization.
AB  - The mutualistic interaction of plants with arbuscular mycorrhizal (AM) fungi is
      characterized by an exchange of nutrients. The plant provides sugars in the form
      of hexoses to the heterotrophic fungus in return for phosphate as well as
      nitrogen, water, and micronutrients. Plant sucrose-cleaving enzymes are predicted
      to play a crucial role in hexose mobilization as these enzymes appear to be
      absent in the fungal partner. Here, recent findings concerning the function of
      plant apoplastic invertases in the AM symbiosis are discussed. Plants with
      modulated enzyme activity in roots and leaves provide additional insight on the
      complexity of the regulation of the AM interaction by apoplastic invertases as
      mycorrhization could be reduced or stimulated depending on the level of invertase
      activity and its tissue-specific expression.

PMID- 19841658
TI  - Actin bundling via LIM domains.
AB  - The LIM domain is defined as a protein-protein interaction module involved in the
      regulation of diverse cellular processes including gene expression and
      cytoskeleton organization. We have recently shown that the tobacco WLIM1, a two
      LIM domain-containing protein, is able to bind to, stabilize and bundle actin
      filaments, suggesting that it participates to the regulation of actin
      cytoskeleton structure and dynamics. In the December issue of the Journal of
      Biological Chemistry we report a domain analysis that specifically ascribes the
      actin-related activities of WLIM1 to its two LIM domains. Results suggest that
      LIM domains function synergistically in the full-length protein to achieve
      optimal activities. Here we briefly summarize relevant data regarding the actin
      related properties/functions of two LIM domain-containing proteins in plants and
      animals. In addition, we provide further evidence of cooperative effects between
      LIM domains by transiently expressing a chimeric multicopy WLIM1 protein in BY2
      cells.

PMID- 19841659
TI  - Actin-based cellular framework for glucose signaling by Arabidopsis hexokinase1.
AB  - Glucose functions in plants both as a metabolic resource as well as a hormone
      that regulates expression of many genes. Arabidopsis hexokinase1 (HXK1) is the
      best understood plant glucose sensor/transducer, yet we are only now appreciating
      the cellular complexity of its signaling functions. We have recently shown that
      one of the earliest detectable responses to plant glucose treatments are
      extensive alterations of cellular F-actin. Interestingly, AtHXK1 is predominantly
      located on mitochondria, yet also can interact with actin. A normal functioning
      actin cytoskeleton is required for HXK1 to act as an effector in glucose
      signaling assays. We have suggested that HXK1 might alter F-actin dynamics and
      thereby influence the formation and/or stabilization of cytoskeleton-bound
      polysomes. In this Addendum, we have extended our initial observations on the
      subcellular targeting of HXK1 and its interaction with F-actin. We then further
      consider the cellular context in which HXK1 might regulate gene expression.

PMID- 19841660
TI  - Endocytic pathways in pollen tube: Implications for in vivo growth regulation.
AB  - By endocytosis eukaryotic cells can take up extracellular components and/or
      plasma membrane proteins for further delivering to endosomes. Although in animal
      cells different endocytic pathways were identified based on the requirement of a
      clathrin coating for vesicle internalization, endocytosis in plant cells still
      require to be fully characterized. The use of positively and negatively charged
      nanogold in combination with Ika, an inhibitor of the clathrindependent
      endocytosis, allowed to dissect the endocytic pathway and revealed the presence
      of clathrin-dependent and clathrin-independent degradative pathways.

PMID- 19841661
TI  - Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene
      function in plant biology.
AB  - Antisense oligodeoxynucleotide (ODN) inhibition emerges as an effective means for
      probing gene function in plant cells. Employing this method we have established
      the importance of the SUSIBA2 transcription factor for regulation of starch
      synthesis in barley endosperm, and arrived at a model for the role of the SUSIBAs
      in sugar signaling and source-sink commutation during cereal endosperm
      development. In this addendum we provide additional data demonstrating the
      suitability of the antisense ODN technology in studies on starch branching enzyme
      activities in barley leaves. We also comment on the mechanism for ODN uptake in
      plant cells.

PMID- 19841662
TI  - A photoreceptor going nowhere but the nucleus.
AB  - Cryptochrome 2 (CRY2) is a blue/UV-A light receptor that regulates light
      inhibition of cell elongation and photoperiodic promotion of floral initiation in
      Arabidopsis. We and others have previously shown that CRY2 is a nuclear protein
      that regulates gene expression to affect plant development. We also showed that
      CRY2 is phosphorylated in response to blue light and the phosphorylated CRY2 is
      most likely active and degraded in blue light. Given that protein translation
      (and probably chromophore attachment) takes place in the cytosol and that a
      photoreceptor would absorb photon instantaneously, it would be interesting to
      know where those inter-connected events occur in the cell. Our results showed
      that freshly synthesized CRY2 photoreceptor is inactive in the cytosol although
      it may be photon-excited, it is imported into the nucleus where the photoreceptor
      is phosphorylated, performs its function, becomes ubiquitinated, and eventually
      gets degraded (Fig. 1).1 To our knowledge, this is the first example in any
      organism that a photoreceptor is shown to complete its post-translational life
      cycle in a single subcellular compartment.

PMID- 19841663
TI  - Multicellular development and protein-protein interactions.
AB  - The macroevolution of organs and tissues in higher plants and animals may have
      been contingent upon the expansion of numerous gene families encoding interacting
      proteins. For example, there are dozens of gene families encoding actin
      cytoskeletal proteins that elaborate intercellular structures influencing
      development. Once gene family members evolve compartmentalized expression,
      protein isovariants are free to coevolve new interacting partners that may be
      incompatible with other related protein networks. Ancient classes of actin
      isovariants and actin-binding proteins are clear examples of such coevolving
      networks. Ectopic expression and suppression studies were used to dissect these
      interactions. In higher plants, the ectopic expression of a reproductive actin
      isovariant in vegetative cell types causes aberrant reorganization of the F-actin
      cytoskeleton and bizarre development of most organs and tissues. In contrast,
      overexpression of vegetative actin in vegetative cell types has little effect.
      The extreme ectopic actin expression phenotypes are suppressed by the coectopic
      expression of reproductive profilin or actin depolymerizing factor (ADF/cofilin)
      isovariants, but not by the overexpression of vegetative profilin or ADF. These
      data provide evidence for the coevolution of organ-specific protein-protein
      interactions. Thus, understanding the contingent relationships between the
      evolution of organ-specific isovariant networks and organ origination may be key
      to explaining multicellular development.

PMID- 19841664
TI  - A large family of genes that share homology with CLE domain in Arabidopsis and
      rice.
AB  - Thirty-one CLAVATA3/ENDOSPERM SURROUNDING REGION (ESR)-related (CLE) proteins are
      encoded in the Arabidopsis genome, and they are supposed to function as
      dodecapeptides with two hydroxyproline residues. Twenty-six synthetic CLE
      peptides, corresponding to the predicted products of the 31 CLE genes, were
      examined in Arabidopsis and rice. Nineteen CLE peptides induced root meristem
      consumption, resulting in the short root phenotype in Arabidopsis and rice,
      whereas no CLE peptides affected the shoot apical meristem in rice. Database
      searches revealed 47 putative CLE genes in the rice genome. Three of the rice CLE
      genes, OsCLE502, OsCLE504 and OsCLE506, encode CLE proteins with multiple CLE
      domains, which are not found in the Arabidopsis genome, and polyproline region
      was found between these CLE domains. These results indicate conserved and/or
      diverse CLE functions in each plant species.

PMID- 19841665
TI  - Do pathogen-specific defense mechanisms contribute to wound-induced resistance in
      tomato?
AB  - A network of shared intermediates/components and/or common molecular outputs in
      biotic and abiotic stress signaling has long been known, but the possibility of
      effective influence between differently triggered stresses (co-protection) is
      less studied. Recent observations show that wounding induces transient protection
      in tomato (Solanum lycopersicum L.) to four pathogens with a range of lifestyles,
      locally and systemically. The contribution of ethylene (ET) in basal but also in
      wound-induced resistance to each pathogen, although dispensable, is demonstrated
      to be positive (Botrytis cinerea, Phytophthora capsici) or negative (Fusarium
      oxysporum, Pseudomonas syringae pv. tomato). Furthermore, the expression of
      several defense markers is influenced locally and/or systemically by wounding and
      ET, and might be part of that core of conserved molecular responses whereby an
      abiotic stress such as wounding imparts co-resistance to biotic stress. In this
      addendum, we speculate on some of the physiological responses to wounding that
      might contribute to the modulation of resistance in a more pathogen-specific
      manner.

PMID- 19841666
TI  - Are there multiple circadian clocks in plants?
AB  - We have reported that Arabidopsis might have genetically distinct circadian
      oscillators in multiple cell-types.1 Rhythms of CHLOROPHYLL A/B BINDING PROTEIN2
      (CAB2) promoter activity are 2.5 h longer in phytochromeB mutants in constant red
      light and in cryptocrome1 cry2 double mutant (hy4-1 fha-1) in constant blue light
      than the wild-type.2 However, we found that cytosolic free Ca(2+) ([Ca(2+)](cyt))
      oscillations were undetectable in these mutants in the same light conditions.1
      Furthermore, mutants of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) have short period
      rhythms of leaf movement but have arrhythmic [Ca(2+)](cyt) oscillations. More
      important, the timing of cab1-1 (toc1-1) mutant has short period rhythms of CAB2
      promoter activity ( approximately 21 h) but, surprisingly, has a wild-type period
      for circadian [Ca(2+)](cyt) oscillations ( approximately 24 h). In contrast, toc1
      2, a TOC1 loss-of-function mutant, has a short period of both CAB2 and
      [Ca(2+)](cyt) rhythms ( approximately 21 h). Here we discuss the difference
      between the phenotypes of toc1-1 and toc1-2 and how rhythms of CAB2 promoter
      activity and circadian [Ca(2+)](cyt) oscillations might be regulated differently.

PMID- 19841667
TI  - Regulation of pollen tube polarity: Feedback loops rule.
AB  - Targeted delivery of immotile sperm through growing pollen tubes is a crucial
      step in achieving sexual reproduction in angiosperms. Unlike diffuse-growing
      cells, the growth of a pollen tube is restricted to the very apical region where
      targeted exocytosis and regulated endocytosis occur. The plant-specific Rho
      GTPases, Rops, are central organizers for pollen tube polarity. Through effector
      binding, Rops regulate the tip-focused Ca(2+) gradient and the actin cytoskeleton
      during pollen tube growth. Therefore, understanding the spatiotemporal regulation
      of Rop activity would reveal how establishment and maintenance of tube polarity
      as well as re-orientation of the growth axis are accomplished. Recent findings
      indicated that two feedback loops may be fundamental in maintaining a fine-tuned
      and dynamic Rop activity. The concerted activities of RopGAP and RopGDI prevent
      lateral diffusion of activated Rop, restricting Rop activity to the apical plasma
      membrane. Conversely, pollen receptor kinases (PRKs) and RopGEFs positively
      feedback regulate Rop activity through protein binding and membrane recruitment.
      Feedback loops would also be essential for pollen tube re-orientation. Shallow
      extracellular cues amplified by concerted activities of feedback loops would lead
      to asymmetric activation of Rop and result in tube re-orientation.

PMID- 19841669
TI  - Salt-avoidance tropism in Arabidopsis thaliana.
AB  - The orientation of plant root growth is modulated by developmental as well as
      environmental cues. Among the environmental factors, gravity has been extensively
      studied because of its overpowering effects in modulating root growth direction.
      However, our knowledge of the effects of other abiotic signals that influence
      root growth direction is largely unknown. Recently, we have shown that high
      salinity can modify root growth direction by inducing rapid amyloplast
      degradation in root columella cells of Arabidopsis thaliana. By exploiting salt
      overly sensitive (sos) mutants and PIN2 expression analyses, we have shown that
      the altered root growth direction in response to salt is mediated by ion
      disequilibrium and is correlated with PIN2 mRNA abundance and expression and
      localization of the protein. Our study demonstrates that the SOS pathway may
      mediate this process. Here we discuss our data from broader perspectives. We
      propose that salt-induced modification of root growth direction is a salt
      avoidance behavior, which is an active adaptive mechanism for plants grown under
      saline conditions. Furthermore, high salinity also stimulates alteration of
      gravitropic growth of shoots. These findings illustrate that plants have a fine
      and sophisticated sensory and communication system that enable plants to
      dynamically and efficiently cope with rapidly changing environment.

PMID- 19841668
TI  - Phosphorylation of A-Type ARR to function as negative regulator of cytokinin
      signal transduction.
AB  - The plant hormone cytokinins regulate diverse aspects of plant growth and
      development. In Arabidopsis, a multi-step TCS system similar to bacterial and
      yeast TCS is used for cytokinin signaling. In a TCS system, a His sensor kinase
      perceives the signal by auto-phosphorylating on a His residue in response to an
      output signal, and the phosphate group is transferred to a conserved Asp residue
      in the receiver domain of the response regulator. The response regulator then
      modulates downstream signaling. Cytokinin multi-step TCS system utilizes an
      additional component, histidine-containing phosphotransfer domain protein (HPT)
      to transfer the phosphate group from a sensor kinase to a response regulator in
      the nucleus. The typical response regulators are classified into either type A or
      B. The type-B ARRs are transcription activators that act as positive regulators
      of cytokinin signaling, whereas most of the type-A ARRs are negative regulators
      of cytokinin signaling. Histidyl-aspartidyl phosphorelays are presumed to be
      essential for this cytokinin signal transduction in plants. Our studies have
      shown that ARR7, an A-type response regulator, negatively regulates cytokinin
      signaling in various aspects by acting as a transcriptional repressor and that
      the phosphorylation of ARR7 is required for these ARR7-regulated cytokinin
      responses. Here I propose potential mechanisms by which the phosphorylation of
      ARRs is involved in regulating cytokinin- mediated gene expression, mainly based
      on biochemical and structural studies of bacterial response regulators. Protein
      protein interaction and DNA-binding studies using the phosphorylated and the un
      phosphorylated forms of the ARR proteins with their structural determination will
      provide molecular understanding of cytokinin-responsive gene regulation by ARRs.

PMID- 19841670
TI  - Exchangers man the pumps: Functional interplay between proton pumps and proton
      coupled Ca exchangers.
AB  - Tonoplast-localised proton-coupled Ca(2+) transporters encoded by
      cation/H(+)exchanger (CAX) genes play a critical role in sequestering Ca(2+) into
      the vacuole. These transporters may function in coordination with Ca(2+) release
      channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recent analysis
      of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a
      variety of phenotypes including sensitivity to abiotic stresses, which indicated
      that these transporters might play a role in mediating the plant's stress
      response. A common feature of these mutants was the perturbation of H(+)-ATPase
      activity at both the tonoplast and the plasma membrane, suggesting a tight
      interplay between the Ca(2+)/H(+) exchangers and H(+) pumps. We speculate that
      indirect regulation of proton flux by the exchangers may be as important as the
      direct regulation of Ca(2+) flux. These results suggest cautious interpretation
      of mutant Ca(2+)/H(+) exchanger phenotypes that may be due to either perturbed
      Ca(2+) or H(+) transport.

PMID- 19841671
TI  - Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7.
AB  - Paraplegin is an m-AAA protease of the mitochondrial inner membrane that is
      linked to hereditary spastic paraplegias. The gene encodes an FtsH-homology
      protease domain in tandem with an AAA+ homology ATPase domain. The protein is
      believed to form a hexamer that uses ATPase-driven conformational changes in its
      AAA-domain to deliver substrate peptides to its protease domain. We present the
      crystal structure of the AAA-domain of human paraplegin bound to ADP at 2.2 A.
      This enables assignment of the roles of specific side chains within the catalytic
      cycle, and provides the structural basis for understanding the mechanism of
      disease mutations. ENHANCED VERSION: This article can also be viewed as an
      enhanced version in which the text of the article is integrated with interactive
      3D representations and animated transitions. Please note that a web plugin is
      required to access this enhanced functionality. Instructions for the installation
      and use of the web plugin are available in Text S1.

PMID- 19841672
TI  - Structural basis for substrate specificity in human monomeric carbonyl
      reductases.
AB  - Carbonyl reduction constitutes a phase I reaction for many xenobiotics and is
      carried out in mammals mainly by members of two protein families, namely aldo
      keto reductases and short-chain dehydrogenases/reductases. In addition to their
      capacity to reduce xenobiotics, several of the enzymes act on endogenous
      compounds such as steroids or eicosanoids. One of the major carbonyl reducing
      enzymes found in humans is carbonyl reductase 1 (CBR1) with a very broad
      substrate spectrum. A paralog, carbonyl reductase 3 (CBR3) has about 70% sequence
      identity and has not been sufficiently characterized to date. Screening of a
      focused xenobiotic compound library revealed that CBR3 has narrower substrate
      specificity and acts on several orthoquinones, as well as isatin or the
      anticancer drug oracin. To further investigate structure-activity relationships
      between these enzymes we crystallized CBR3, performed substrate docking, site
      directed mutagenesis and compared its kinetic features to CBR1. Despite high
      sequence similarities, the active sites differ in shape and surface properties.
      The data reveal that the differences in substrate specificity are largely due to
      a short segment of a substrate binding loop comprising critical residues
      Trp229/Pro230, Ala235/Asp236 as well as part of the active site formed by
      Met141/Gln142 in CBR1 and CBR3, respectively. The data suggest a minor role in
      xenobiotic metabolism for CBR3. ENHANCED VERSION: This article can also be viewed
      as an enhanced version in which the text of the article is integrated with
      interactive 3D representations and animated transitions. Please note that a web
      plugin is required to access this enhanced functionality. Instructions for the
      installation and use of the web plugin are available in Text S1.

PMID- 19841673
TI  - Crystal structure of the N-acetylmannosamine kinase domain of GNE.
AB  - BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional
      enzyme that plays a key role in sialic acid biosynthesis. Mutations of the GNE
      protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka
      myopathy. GNE is the only human protein that contains a kinase domain belonging
      to the ROK (repressor, ORF, kinase) family. PRINCIPAL FINDINGS: We solved the
      structure of the GNE kinase domain in the ligand-free state. The protein exists
      predominantly as a dimer in solution, with small populations of monomer and
      higher-order oligomer in equilibrium with the dimer. Crystal packing analysis
      reveals the existence of a crystallographic hexamer, and that the kinase domain
      dimerizes through the C-lobe subdomain. Mapping of disease-related missense
      mutations onto the kinase domain structure revealed that the mutation sites could
      be classified into four different groups based on the location - dimer interface,
      interlobar helices, protein surface, or within other secondary structural
      elements. CONCLUSIONS: The crystal structure of the kinase domain of GNE provides
      a structural basis for understanding disease-causing mutations and a model of
      hexameric wild type full length enzyme. ENHANCED VERSION: This article can also
      be viewed as an enhanced version in which the text of the article is integrated
      with interactive 3D representations and animated transitions. Please note that a
      web plugin is required to access this enhanced functionality. Instructions for
      the installation and use of the web plugin are available in Text S1.

PMID- 19841674
TI  - Crystal structure of the PIM2 kinase in complex with an organoruthenium
      inhibitor.
AB  - BACKGROUND: The serine/threonine kinase PIM2 is highly expressed in human
      leukemia and lymphomas and has been shown to positively regulate survival and
      proliferation of tumor cells. Its diverse ATP site makes PIM2 a promising target
      for the development of anticancer agents. To date our knowledge of catalytic
      domain structures of the PIM kinase family is limited to PIM1 which has been
      extensively studied and which shares about 50% sequence identity with PIM2.
      PRINCIPAL FINDINGS: Here we determined the crystal structure of PIM2 in complex
      with an organoruthenium complex (inhibition in sub-nanomolar level). Due to its
      extraordinary shape complementarity this stable organometallic compound is a
      highly potent inhibitor of PIM kinases. SIGNIFICANCE: The structure of PIM2
      revealed several differences to PIM1 which may be explored further to generate
      isoform selective inhibitors. It has also demonstrated how an organometallic
      inhibitor can be adapted to the binding site of protein kinases to generate
      highly potent inhibitors. ENHANCED VERSION: This article can also be viewed as an
      enhanced version in which the text of the article is integrated with interactive
      3D representations and animated transitions. Please note that a web plugin is
      required to access this enhanced functionality. Instructions for the installation
      and use of the web plugin are available in Text S1.

PMID- 19841676
TI  - A new method for publishing three-dimensional content.

PMID- 19841675
TI  - Structural studies of a four-MBT repeat protein MBTD1.
AB  - BACKGROUND: The Polycomb group (PcG) of proteins is a family of important
      developmental regulators. The respective members function as large protein
      complexes involved in establishment and maintenance of transcriptional repression
      of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing
      protein 1, is one such PcG protein. MBTD1 contains four MBT repeats.
      METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structure of MBTD1
      (residues 130-566aa covering the 4 MBT repeats) at 2.5 A resolution by X-ray
      crystallography. The crystal structure of MBTD1 reveals its similarity to another
      four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones.
      Fluorescence polarization experiments confirmed that MBTD1 preferentially binds
      mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known
      MBT-peptide complex structures characterized to date do not exhibit strong
      histone peptide sequence selectivity, and use a "cavity insertion recognition
      mode" to recognize the methylated lysine with the deeply buried methyl-lysine
      forming extensive interactions with the protein while the peptide residues
      flanking methyl-lysine forming very few contacts [1]. Nevertheless, our
      mutagenesis data based on L3MBTL1 suggested that the histone peptides could not
      bind to MBT repeats in any orientation. CONCLUSIONS: The four MBT repeats in
      MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat
      proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones
      through one of its four MBT repeats utilizing a semi-aromatic cage. ENHANCED
      VERSION: This article can also be viewed as an enhanced version in which the text
      of the article is integrated with interactive 3D representations and animated
      transitions. Please note that a web plugin is required to access this enhanced
      functionality. Instructions for the installation and use of the web plugin are
      available in Text S1.

PMID- 19841677
TI  - Computational data mining in cancer bioinformatics and cancer epidemiology.

PMID- 19841679
TI  - A Case Report of Intraductal Papillary-Mucinous Neoplasm of the Pancreas Showing
      Morphologic Transformation during Followup Periods.
AB  - A 64-year-old man underwent MRCP for further examination of gallbladder stones
      and IPMN of branch-type (IPMN-Br) was pointed out. Yearly MRCP had revealed the
      gradual increase of the cystic components, marked dilation of the main pancreatic
      duct (MPD), and filling defects in the MPD. After follow-up for three years, he
      underwent pancreatoduodenectomy. Histologically, the dilated MPD and connecting
      dilated branch ducts were filled with nodular growth of tumor cells consisting of
      gastric-type adenoma with pyloric gland-like structures. In the MPD, a transition
      from gastric-type adenoma to intestinal-type carcinoma was observed. In addition,
      in a dilated branch duct, some components of intestinal-type carcinoma with
      marked arborizing structures were observed. A minimally invasion was observed
      around branch ducts. Immunohistochemistry revealed diffuse nuclear accumulation
      of PCNA and Ki67 in the tumor cells of branch dusts. Our observations suggest
      that the secondary infiltration to the MPD of IPMN-Br and IPMN-Br possesses
      malignant potential for microinvasion.

PMID- 19841680
TI  - Prognostic factors in patients with multiple recurrences of well-differentiated
      thyroid carcinoma.
AB  - Introduction. Patients with multiple recurrences of well-differentiated thyroid
      carcinoma (WDTC) have markedly reduced overall survival when compared with those
      who have </=1 recurrence of their disease. The purpose of this investigation is
      to identify prognostic factors for mortality in this subgroup. Methods. Patients
      with multiple recurrences of WDTC were retrospectively identified from the
      thyroid cancer database at Mount Sinai Hospital, Toronto (1963-2000). Data on
      patient, tumor, and recurrence characteristics were collected, and each patient
      was given a MACIS score. Results. A total of 31 patients were identified (11
      male, 20 female; 16-83 years). Using univariate analysis, age >45, stage III/IV
      disease, distant metastasis, vascular invasion, MACIS score >6, and time to
      recurrence of <12 months were found to be significant predictors for mortality in
      this subgroup. Conclusions. Patients with multiple recurrences of WDTC follow a
      distinct clinical course, marked with multiple treatment failures and a
      substantial risk of mortality.

PMID- 19841678
TI  - MicroRNA implications across neurodevelopment and neuropathology.
AB  - MicroRNAs (miRNAs) have rapidly emerged as biologically important mediators of
      posttranscriptional and epigenetic regulation in both plants and animals. miRNAs
      function through a variety of mechanisms including mRNA degradation and
      translational repression; additionally, miRNAs may guide gene expression by
      serving as transcription factors. miRNAs are highly expressed in human brain.
      Tissue and cell type-specific enrichments of certain miRNAs within the nervous
      system argue for a biological significance during neurodevelopmental stages. On
      the other hand, a large number of studies have reported links between alterations
      of miRNA homeostasis and pathologic conditions such as cancer, heart diseases,
      and neurodegeneration. Thus, profiles of distinct or aberrant miRNA signatures
      have most recently surged as one of the most fascinating interests in current
      biology. Here, the most recent insights into the involvement of miRNAs in the
      biology of the nervous system and the occurrence of neuropathological disorders
      are reviewed and discussed.

PMID- 19841681
TI  - Decreased polyunsaturated Fatty Acid content contributes to increased survival in
      human colon cancer.
AB  - Among diet components, some fatty acids are known to affect several stages of
      colon carcinogenesis, whereas others are probably helpful in preventing tumors.
      In light of this, our aim was to determine the composition of fatty acids and the
      possible correlation with apoptosis in human colon carcinoma specimens at
      different Duke's stages and to evaluate the effect of enriching human colon
      cancer cell line with the possible reduced fatty acid(s). Specimens of carcinoma
      were compared with the corresponding non-neoplastic mucosa: a significant
      decrease of arachidonic acid, PPARalpha, Bad, and Bax and a significant increase
      of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in
      apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid.
      It induced apoptosis in a dose- and time-dependent manner via induction of
      PPARalpha that, in turn, decreased COX-2. In conclusion, the reduced content of
      arachidonic acid is likely related to carcinogenic process decreasing the
      susceptibility of cancer cells to apoptosis.

PMID- 19841682
TI  - Automation of cDNA synthesis and labelling improves reproducibility.
AB  - BACKGROUND: Several technologies, such as in-depth sequencing and microarrays,
      enable large-scale interrogation of genomes and transcriptomes. In this study, we
      asses reproducibility and throughput by moving all laboratory procedures to a
      robotic workstation, capable of handling superparamagnetic beads. Here, we
      describe a fully automated procedure for cDNA synthesis and labelling for
      microarrays, where the purification steps prior to and after labelling are based
      on precipitation of DNA on carboxylic acid-coated paramagnetic beads. RESULTS:
      The fully automated procedure allows for samples arrayed on a microtiter plate to
      be processed in parallel without manual intervention and ensuring high
      reproducibility. We compare our results to a manual sample preparation procedure
      and, in addition, use a comprehensive reference dataset to show that the protocol
      described performs better than similar manual procedures. CONCLUSIONS: We
      demonstrate, in an automated gene expression microarray experiment, a reduced
      variance between replicates, resulting in an increase in the statistical power to
      detect differentially expressed genes, thus allowing smaller differences between
      samples to be identified. This protocol can with minor modifications be used to
      create cDNA libraries for other applications such as in-depth analysis using next
      generation sequencing technologies.

PMID- 19841684
TI  - Increased porphyrins in primary liver cancer mainly reflect a parallel liver
      disease.
AB  - Hepatic porphyries have been associated with an increased risk of primary liver
      cancer (PLC), which on the other hand may cause an increased porphyrin
      production. To evaluate the role of an underlying liver disorder we analyzed
      porphyrins in patients with hepatocellular carcinoma (HCC) (n = 65),
      cholangiocellular carcinoma (n = 3), or suspected PLC, which turned out to be
      metastases (n = 18) or a benign disorder (n = 11). None of the patients had a
      family history of porphyry or clinical signs of porphyry. Increased
      aminolevulinic acid or porphyrin values were common not only in patients with PLC
      (43%) but also in metastatic (50%) and benign (64%) liver disorders. The
      corresponding proportion for HCC patients with liver cirrhosis (55%) was higher
      (P < .05) than in those without cirrhosis (17%). We conclude that symptomatic
      porphyries are unusual in PLC, whereas elevated urinary and/or faecal porphyrins
      are common, primarily reflecting a parallel liver disease and not the PLC.

PMID- 19841683
TI  - Using a state-space model and location analysis to infer time-delayed regulatory
      networks.
AB  - Computational gene regulation models provide a means for scientists to draw
      biological inferences from time-course gene expression data. Based on the state
      space approach, we developed a new modeling tool for inferring gene regulatory
      networks, called time-delayed Gene Regulatory Networks (tdGRNs). tdGRN takes time
      delayed regulatory relationships into consideration when developing the model. In
      addition, a priori biological knowledge from genome-wide location analysis is
      incorporated into the structure of the gene regulatory network. tdGRN is
      evaluated on both an artificial dataset and a published gene expression data set.
      It not only determines regulatory relationships that are known to exist but also
      uncovers potential new ones. The results indicate that the proposed tool is
      effective in inferring gene regulatory relationships with time delay. tdGRN is
      complementary to existing methods for inferring gene regulatory networks. The
      novel part of the proposed tool is that it is able to infer time-delayed
      regulatory relationships.

PMID- 19841685
TI  - Profound intraoperative metabolic acidosis and hypotension in a child undergoing
      multilevel spinal fusion.
AB  - The prone position may cause cardiovascular system depression. Yet, the
      mechanisms involved and preemptive measures are not well understood (Edgcombe et
      al. (2008)). During spinal surgery in the prone position, hypotension may occur.
      Implicated factors include prolonged abdominal compression impeding venous return
      resulting in increased blood loss, decreased cardiovascular reserve, and the use
      of total intravenous anesthesia (TIVA) which has been shown to blunt the
      sympathetic response more than inhalation anesthesia. We present a case of
      hypotension during spinal surgery with all its challenges. Hypotension and
      acidosis persisted despite all supporting measures, and only to improve with
      supine positioning. Differential diagnosis for such an event are discussed.
      Although abdominal compression may not be obvious before the start of surgery,
      compressing the spine during surgery may lead to abdominal compression and
      hypoperfusion to abdominal organs.

PMID- 19841686
TI  - STIFDB-Arabidopsis Stress Responsive Transcription Factor DataBase.
AB  - Elucidating the key players of molecular mechanism that mediate the complex
      stress-responses in plants system is an important step to develop improved
      variety of stress tolerant crops. Understanding the effects of different types of
      biotic and abiotic stress is a rapidly emerging domain in the area of plant
      research to develop better, stress tolerant plants. Information about the
      transcription factors, transcription factor binding sites, function annotation of
      proteins coded by genes expressed during abiotic stress (for example: drought,
      cold, salinity, excess light, abscisic acid, and oxidative stress) response will
      provide better understanding of this phenomenon. STIFDB is a database of abiotic
      stress responsive genes and their predicted abiotic transcription factor binding
      sites in Arabidopsis thaliana. We integrated 2269 genes upregulated in different
      stress related microarray experiments and surveyed their 1000 bp and 100 bp
      upstream regions and 5'UTR regions using the STIF algorithm and identified
      putative abiotic stress responsive transcription factor binding sites, which are
      compiled in the STIFDB database. STIFDB provides extensive information about
      various stress responsive genes and stress inducible transcription factors of
      Arabidopsis thaliana. STIFDB will be a useful resource for researchers to
      understand the abiotic stress regulome and transcriptome of this important model
      plant system.

PMID- 19841687
TI  - On the use of electrooculogram for efficient human computer interfaces.
AB  - The aim of this study is to present electrooculogram signals that can be used for
      human computer interface efficiently. Establishing an efficient alternative
      channel for communication without overt speech and hand movements is important to
      increase the quality of life for patients suffering from Amyotrophic Lateral
      Sclerosis or other illnesses that prevent correct limb and facial muscular
      responses. We have made several experiments to compare the P300-based BCI speller
      and EOG-based new system. A five-letter word can be written on average in 25
      seconds and in 105 seconds with the EEG-based device. Giving message such as
      "clean-up" could be performed in 3 seconds with the new system. The new system is
      more efficient than P300-based BCI system in terms of accuracy, speed,
      applicability, and cost efficiency. Using EOG signals, it is possible to improve
      the communication abilities of those patients who can move their eyes.

PMID- 19841688
TI  - The changing presentation of choledochal cyst disease: an incidental diagnosis.
AB  - BACKGROUND: Choledochal cysts are uncommon biliary lesions. Due to the evolution
      of imaging and laparoscopic surgery, we sought to describe our last 3 years
      experience with the presentation and management of choledochal cysts in adults.
      METHODS: A retrospective review of a prospectively established database of adults
      who were managed for primary choledochal cyst disease between 2005 and 2008 was
      performed. RESULTS: Between 8/2005 and 8/2008, 14 adults were managed for primary
      choledochal cyst disease. The average age was 41 years (range 17-86) and 79% were
      female. Presentations included biliary sepsis (3), pancreatitis (2), abdominal
      pain (3), or painless jaundice (1). Three patients had the cyst found during
      laparoscopic cholecystectomy, and two had an incidental finding after CT scan for
      an unrelated issue. The length of stay for those who had the cyst removed was 7.8
      days (range 5-11). There were no operative or post-operative complications.
      CONCLUSIONS: Over the last 3 years 36% of our patients with choledochal cysts
      presented after incidental finding, either during a laparoscopic operation or
      after a CT scan for an unrelated problem. Increasing utilization of laparoscopy
      and CT scan for abdominal complaints has lead to a change in the pattern of
      presentation.

PMID- 19841689
TI  - Monoclonal gammopathies--clinical and laboratory issues.

PMID- 19841691
TI  - Current trends in the diagnosis, therapy and monitoring of the monoclonal
      gammopathies.
AB  - This paper provides an overview of developments in the diagnosis, therapy and
      monitoring of the monoclonal gammopathies, particularly multiple myeloma and AL
      amyloidosis. Consensus statements outlining diagnostic criteria for monoclonal
      gammopathy of undetermined significance (MGUS), myeloma and amyloidosis have been
      recently published. Understanding of the biology and pathogenesis of myeloma has
      accelerated in the last decade and provides the basis for improved
      prognostication and therapeutic interventions. Myeloma therapy has progressed
      with the introduction of autologous and allogeneic stem cell transplantation and
      the recent introduction of the novel agents, thalidomide, lenalidomide and
      bortezomib. Each of these therapeutic advances has contributed to the improved
      survival seen in this patient population. Similar treatment advances are
      occurring in AL amyloidosis. While serum and urine electrophoretic analysis
      remain the "gold standard" laboratory techniques for the accurate and cost
      effective monitoring of the monoclonal gammopathies, new tests such as the free
      light chain assays have a complementary role. New guidelines for the monitoring
      of both myeloma and AL amyloidosis have been produced that incorporate these
      newer tests.

PMID- 19841692
TI  - Screening panels for monoclonal gammopathies: time to change.
AB  - The introduction of quantitative assays for serum free light chains (FLC) has
      changed the approach to screening for monoclonal gammopathies. Recent guidelines
      from the International Myeloma Working Group have recommended the use of serum
      protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and FLC as
      the screening panel unless primary amyloidosis (AL) is suspected. If screening
      for AL, then urine IFE should also be performed. We discuss the background for
      these recommendations as well as data showing that SPEP and FLC alone may provide
      a simplified screening panel for detecting multiple myeloma (MM) and
      Waldenstrom's macroglobulinaemia (WM) with little loss of diagnostic sensitivity.
      If AL is suspected, we support the recommendation to include serum and urine IFE.
      The selective use of serum and urine IFE requires that clinical judgment be
      integral to ordering screening panels for detection of monoclonal gammopathies.

PMID- 19841693
TI  - Significance of abnormal protein bands in patients with multiple myeloma
      following autologous stem cell transplantation.
AB  - AIM: We studied the characteristics of small abnormal protein bands (APB)
      (including oligoclonal bands and new apparent monoclonal bands) that are
      frequently detected by serum protein electrophoresis (SPEP) and isoelectric
      focusing (IEF) in the post-autologous stem cell transplant setting. METHODS: In a
      retrospective analysis of patients with multiple myeloma undergoing
      transplantation, paraprotein identity and quantification were performed using
      standard immunofixation electrophoresis. The nature of any new bands was
      determined by IEF which distinguished between oligoclonal bands and apparent
      monoclonal bands. RESULTS: Of 49 myeloma cases, the median follow-up was 33.7
      months (range, 5.6-97.5 months) and 24 patients had relapsed. Thirty six (73%)
      developed APB. 22 patients had more than one episode of APB and 6 patients had
      more than 2 episodes resulting in a total of 69 episodes of APB observed post
      transplant. IEF demonstrated 54 of these APB were oligoclonal bands and 15
      appeared to be monoclonal. Of the 15 episodes of apparent monoclonal bands, 10
      had differing heavy or light chain restriction compared to the original myeloma
      paraprotein and 5 had the same heavy and light chain restriction but different
      band location in the SPEP lane. Ten of these apparent monoclonal bands resolved,
      5 persisted, and only one represented true disease progression. The presence of
      APB impacted favourably on event-free survival (p=0.05). CONCLUSION: Small APB
      are very frequent post-transplant for myeloma, and IEF can identify these APB as
      oligoclonal or monoclonal. Apparent monoclonal bands may represent relapsed
      disease, but in the vast majority of cases it does not, and most likely
      represents a transient phenomenon representing regeneration of a limited immune
      response.

PMID- 19841694
TI  - Serum and urine electrophoresis for detection and identification of monoclonal
      proteins.
AB  - Electrophoresis may be defined as the separation of charged particles in a
      uniform electric field. For a particular system of electrophoresis, the voltage
      is held constant as are the pH and ionic strength of the suspending medium.
      Tiselius, using a moving boundary liquid system, separated serum proteins by
      electrophoresis into four components in 1937. Paper electrophoresis, popular in
      the 1950s, provided the rst solid electrophoresis support. The fragility of paper
      as a support medium saw the introduction of the more robust cellulose acetate a
      decade later. An improvement in resolution was subsequently gained by using
      agarose gel, which, in serum samples, gave 5 bands of separation. In the late
      1980s, high resolution agarose gels were introduced which produced at least 6
      bands, and depending on the system, as many as 17 bands in serum. Fully automated
      serum electrophoresis commenced in the 1990s with the introduction of capillary
      electrophoresis (CE), a reintroduction of a liquid medium but with exquisite
      resolution compared to Tiselius' procedure. Using CE instrumentation it is
      possible to program a sequence of samples and leave them overnight to be
      processed.Amalgamation of laboratories with an increasing number of patient
      samples was probably the reason for the semi-automation of gel electrophoresis.
      The introduction of the Helena SPIFE and Sebia Hydrasys gel systems provided ways
      of electrophoresing over a hundred serum samples per day. There is certainly a
      role for such instrumentation in electrophoresis laboratories today.

PMID- 19841695
TI  - Isoelectric focusing, blotting and probing methods for detection and
      identification of monoclonal proteins.
AB  - Isoelectric focusing (IEF) is a technique of exquisite resolution and high
      sensitivity. When applied to human biological fluids using conventional protein
      stains it is capable of detecting down to about 100 mg of protein/L. When
      combined with blotting and probing techniques it can get down to less than 1
      mg/L. The exquisite resolution enables a greater discrimination between the
      various immunoglobulin abnormalities encountered in the clinical laboratory.

PMID- 19841696
TI  - Quantitative serum free light chain assay--analytical issues.
AB  - Serum free light chain (FLC) assay is an important advance in the diagnosis and
      monitoring of monoclonal light chain diseases and a complementary test to serum
      protein electrophoresis and immunofixation. Immunoturbidimetric and
      immunonephelometric assays for serum FLC are available on routine chemistry
      analysers and can detect FLC down to approximately 1 mg/L. These assays use
      polyclonal anti-human FLC antisera and require acceptable imprecision,
      specificity, accuracy, and reproducibility between reagent batches to prevent
      under- or over-estimation of FLC concentration. Assay imprecision determined
      between reagent lots has a variation of 8-45% for FLC concentrations and 17-32%
      for the calculated kappa/lambda FLC ratio. Dilution studies indicate some over
      recovery of FLC, which may depend upon the dilution matrix. However, greater
      discrepancies are underestimation from nonlinear reactions and overestimation
      possibly from interferences or multi-reactivity to polymeric FLC. Nonlinear
      monoclonal FLC give concentrations which are 2- to 6-fold increased at higher
      sample dilution and FLC measured on different platforms may not give the same
      results. Laboratory staff and clinicians should be aware of the analytical
      limitations of the FLC assay. Assay imprecision, especially with different lots
      of FLC reagent, may have a significant effect on changes in the FLC concentration
      and kappa/lambda FLC ratio. Sample dilution anomalies have the potential to
      confound result interpretation for patients with monoclonal light chain disease.
      These issues, if not adequately appreciated, have the potential to mislead
      clinical diagnosis and assessment of response to therapy.

PMID- 19841697
TI  - Reporting of quantitative protein electrophoresis in Australia and New Zealand: a
      call for standardisation.
AB  - BACKGROUND: The lack of guidelines on reporting standards for protein
      electrophoresis may have led to significant differences in reports from different
      laboratories. OBJECTIVE: To determine the extent of variation in reporting of
      protein electrophoresis results in Australia and New Zealand. METHOD:
      Questionnaires were distributed to laboratories throughout Australia and New
      Zealand asking about protein electrophoresis practices and reporting. RESULTS:
      Extensive variation was found in the following reporting practices: (a) units for
      urine Bence Jones protein (BJP); (b) reporting absence of a paraprotein rather
      than a normal pattern; (c) numerical reporting of all protein fractions or only
      the paraprotein; (d) warning of possible inaccuracy in the serum immunoglobulin
      result of the paraprotein type; (e) co-migration of a paraprotein with a normal
      serum protein; (f) use of a confirmatory test when a known paraprotein is no
      longer detectable. CONCLUSIONS: A working party should be established to make
      recommendations on the reporting of protein electrophoresis. Implementation of
      such recommendations should reduce both report variation between laboratories and
      the risk of misinterpretation of reports.

PMID- 19841699
TI  - Serum alanine aminotransferase levels, hematocrit rate and body weight
      correlations before and after hemodialysis session.
AB  - PURPOSE: To evaluate alanine aminotransferase levels before and after a
      hemodialysis session and to correlate these values with the hematocrit rate and
      weight loss during hemodialysis. PATIENTS AND METHODS: The serum alanine
      aminotransferase levels, hematocrit rate and body weight were measured and
      correlated before and after a single hemodialysis session for 146 patients with
      chronic renal failure. An receiver operating characteristic (ROC) curve for the
      serum alanine aminotransferase levels collected before and after hemodialysis was
      plotted to identify hepatitis C virus-infected patients. RESULTS: The mean weight
      loss of the 146 patients during hemodialysis was 5.3% (p < 0.001). The mean
      alanine aminotransferase levels before and after hemodialysis were 18.8 and 23.9
      IU/, respectively, denoting a significant 28.1% increase. An equally significant
      increase of 16.4% in the hematocrit rate also occurred after hemodialysis. The
      weight loss was inversely correlated with the rise in both the alanine
      aminotransferase level (r = 0.3; p < 0.001) and hematocrit rate (r = 0.5; p <
      0.001). A direct correlation was found between the rise in alanine
      aminotransferase levels and the hematocrit during the hemodialysis session (r =
      0.4; p < 0.001). Based on the ROC curve, the upper limit of the normal alanine
      aminotransferase level should be reduced by 40% relative to the upper limit of
      normal if the blood samples are collected before the hemodialysis session or by
      60% if blood samples are collected after the session. CONCLUSION: In the present
      study, significant elevations in the serum alanine aminotransferase levels and
      hematocrit rates occurred in parallel to a reduction in body weight after the
      hemodialysis session. These findings suggest that one of the factors for low
      alanine aminotransferase levels prior to hemodialysis could be hemodilution in
      patients with chronic renal failure.

PMID- 19841700
TI  - Childhood eye diseases in southwestern Nigeria: a tertiary hospital study.
AB  - BACKGROUND: Eye diseases are important cause of medical consultation in children,
      with the spectrum varying in different localities. This study aimed to determine
      the spectrum of childhood eye diseases in a tertiary hospital serving rural and
      semi-rural communities. METHODS: We conducted a retrospective review of all
      patients less than 15 years old who presented to the eye clinic of Wesley Guild
      Hospital Ilesa, Nigeria between January 2001 and December 2006. Data on age at
      presentation, age at onset of disease, sex and diagnosis were collected and
      analyzed using SPSS. A p value less than 0.05 was considered statistically
      significant. RESULTS: We evaluated the reports of 286 children, with a
      male:female ratio of 1:1.1. Children aged 11-15 years made up the largest group
      (p=0.013). Ocular trauma (21.7%), allergic conjunctivitis (17.8%), infections of
      the eye and its adnexa (15.4%) and refractive errors (14.3%) were the most common
      conditions. Ocular injury was more common in males (p=0.002) and children aged 6
      10 years, and 87.1% of these cases were a closed globe injury. Infections were
      seen more commonly among females and children aged 0-5 years, with keratitis
      representing 40.9% of these cases. Congenital eye disease represented 13.3% of
      childhood eye diseases. CONCLUSION: The prevalent childhood eye diseases recorded
      here can lead to absenteeism from school and are potentially blinding. Health
      education aimed at the prevention of ocular trauma and prompt presentation for
      the management of other eye diseases should be encouraged.

PMID- 19841701
TI  - A contralateral eye study comparing apodized diffractive and full diffractive
      lenses: wavefront analysis and distance and near uncorrected visual acuity.
AB  - PURPOSE: To evaluate intraindividual visual acuity, wavefront errors and
      modulation transfer functions in patients implanted with two diffractive
      multifocal intraocular lenses. METHODS: This prospective study examined 40 eyes
      of 20 cataract patients who underwent phacoemulsification and implantation of a
      spherical multifocal ReSTOR intraocular lens in one eye and an aspheric Tecnis
      ZM900 multifocal intraocular lens in the other eye. The main outcome measures,
      over a 3-month follow-up period, were the uncorrected photopic distance and near
      visual acuity and the defocus curve. The visual acuity was converted to logMAR
      for statistical analysis and is presented in decimal scale. The wavefront error
      and modulation transfer function were also evaluated in both groups. RESULTS: At
      the 3-month postoperative visit, the mean photopic distance uncorrected visual
      acuity (UCVA) was 0.74 +/- 0.20 in the ReSTOR group and 0.76 +/- 0.22 in the
      Tecnis group (p=0.286). The mean near UCVA was 0.96 +/- 0.10 in the ReSTOR group
      and 0.93 +/- 0.14 in the Tecnis group (p=0.963). The binocular defocus curve
      showed measurements between the peaks better than 0.2 logMAR. The total
      aberration, higher-order aberration and coma aberration were not significantly
      different between the groups. The spherical aberration was significantly lower in
      the Tecnis group than in the ReSTOR group. (p=0.004). Both groups performed
      similarly for the modulation transfer function. CONCLUSION: The ReSTOR SN60D3 and
      Tecnis ZM 900 intraocular lenses provided similar photopic visual acuity at
      distance and near. The diffractive intraocular lenses studied provided a low
      value of coma and spherical aberrations, with the Tecnis intraocular lens having
      a statistically lower spherical aberration compared to the ReSTOR intraocular
      lens. In the 5 mm pupil diameter analyses, both intraocular lens groups showed
      similar modulation transfer functions.

PMID- 19841702
TI  - Treatment of cutaneous tumors with topical 5% imiquimod cream.
AB  - INTRODUCTION: There are various approaches to the treatment of cutaneous tumors;
      one of them is treatment with imiquimod, a synthetic toll-like receptor agonist
      with a low molecular weight that offers a topical, noninvasive, and non-surgical
      therapeutic option. The main objective of our study was to provide data on 89
      patients who used a 5% imiquimod cream for the treatment of cutaneous tumors at
      the Cutaneous Oncology Group of the Dermatology Department of Hospital das
      Clinicas from 2003 to 2008. MATERIALS AND METHODS: Here, we present our
      experience in the treatment of 123 cutaneous tumors of various types, including
      basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease,
      erythroplasia of Queyrat, Paget's disease, and trichoepithelioma, with 5%
      imiquimod cream from 2003 to 2008 in the Cutaneous Oncology Group of the
      Dermatology Department of Hospital das Clinicas. Patients were divided into two
      separate groups according to their diagnosis and comorbidities; these
      comorbidities included epidermodysplasia verruciformis, xeroderma pigmentosum,
      albinism, basal cell nevus syndrome, Brooke-Spiegler syndrome, HIV, chronic
      lymphocytic leukemia, B-cell lymphoma, and kidney transplantation. Treatment
      duration, response to imiquimod, follow-up, recurrence, and local and systemic
      reactions associated with use of the drug were analyzed. Epidemiological data
      were obtained and cure rates were calculated. RESULTS: The ratio of women to men
      was 1.28:1, and the mean age was 63.1 years. Tumors were located mainly on the
      face, back, trunk, and legs. For patients with comorbidities, the overall cure
      rate was 38%. These specific patients demonstrated cure rates of 83.5% for
      superficial BCC and 50% for Bowen's disease. Aggressive BCC and superficial and
      nodular BCC did not present a good response to treatment. Trichoepitheliomas and
      nodular BCC showed a partial response, and erythroplasia of Queyrat showed a
      complete response. For patients without comorbidities, the overall cure rate was
      73%. For these patients, the cure rates were 85.7% for superficial and nodular
      BCC, 88% for superficial BCC, 57% for Bowen's disease, 50% for nodular BCC, and
      50% for aggressive BCC. One SCC lesion demonstrated a complete response, and
      tumors caused by Paget's disease and erythroplasia of Queyrat presented a partial
      response. None of the tumors considered as clinically cured recurred. Thirty
      seven lesions demonstrated no response to imiquimod. Having a cutaneous
      comorbidity, high-risk tumors such as mixed aggressive BCC (sclerodermiform or
      micronodular), nodular BCC, or Bowen's disease, and presenting no local reaction
      to imiquimod were considered as risk factors for a worse prognosis. We
      demonstrate that patients with no response to imiquimod, even when they
      demonstrated no local reaction, can undergo another cycle of six weeks of
      imiquimod treatment and show a complete response. The healing pattern led to good
      cosmetic outcomes, and the side effects were tolerable. CONCLUSIONS: Our
      experience confirms imiquimod as an effective treatment option for several types
      of cutaneous tumors, especially in patients without the cutaneous comorbidities
      cited above and with low-risk tumors. Imiquimod has a relatively low cost
      compared to other therapeutic options and can be delivered via ambulatory care to
      patients with surgery contraindications, and its side effects are tolerable.

PMID- 19841703
TI  - Combining cognitive screening tests for the evaluation of mild cognitive
      impairment in the elderly.
AB  - OBJECTIVE: To determine the accuracy of the Mini-Mental State Examination
      combined with the Verbal Fluency Test and Clock Drawing Test for the
      identification of patients with mild cognitive impairment and Alzheimer's disease
      (AD). METHOD: These tests were used to evaluate cognitive function in 247 older
      adults. Subjects were divided into three groups according to their cognitive
      state: mild cognitive impairment (n=83), AD (n=81), cognitively unimpaired
      controls (n=83), based on clinical and neuropsychological data. The diagnostic
      accuracy of each test for discriminating between these diagnostic groups (mild
      cognitive impairment or AD vs. controls) was examined with the aid of Receiver
      Operating Characteristic (ROC) curves. Additionally, we evaluated the benefit of
      the combination of tests on diagnostic accuracy. RESULTS: Although they were
      accurate enough for the identification of Alzheimer's disease, neither test alone
      proved adequate for the correct separation of patients with mild cognitive
      impairment from healthy subjects. Combining these tests did not improve
      diagnostic accuracy, as compared to the Mini-Mental State Examination alone, in
      the identification of patients with mild cognitive impairment or Alzheimer's
      disease. CONCLUSIONS: The present data do not warrant the combined use of the
      Mini-Mental State Examination, the Verbal Fluency Test and the Clock Drawing Test
      as a sufficient diagnostic schedule in screening for mild cognitive impairment.
      The present data do not support the notion that the combination of test scores is
      better that the use of Mini-Mental State Examination scores alone in the
      screening for Alzheimer's disease.

PMID- 19841704
TI  - Development and evaluation of a head-controlled human-computer interface with
      mouse-like functions for physically disabled users.
AB  - OBJECTIVES: The objectives of this study were to develop a pointing device
      controlled by head movement that had the same functions as a conventional mouse
      and to evaluate the performance of the proposed device when operated by
      quadriplegic users. METHODS: Ten individuals with cervical spinal cord injury
      participated in functional evaluations of the developed pointing device. The
      device consisted of a video camera, computer software, and a target attached to
      the front part of a cap, which was placed on the user's head. The software
      captured images of the target coming from the video camera and processed them
      with the aim of determining the displacement from the center of the target and
      correlating this with the movement of the computer cursor. Evaluation of the
      interaction between each user and the proposed device was carried out using 24
      multidirectional tests with two degrees of difficulty. RESULTS: According to the
      parameters of mean throughput and movement time, no statistically significant
      differences were observed between the repetitions of the tests for either of the
      studied levels of difficulty. CONCLUSIONS: The developed pointing device
      adequately emulates the movement functions of the computer cursor. It is easy to
      use and can be learned quickly when operated by quadriplegic individuals.

PMID- 19841705
TI  - Relationship of BODE Index to functional tests in chronic obstructive pulmonary
      disease.
AB  - OBJECTIVE: To determine if there is a correlation between the BODE Index and
      variables assessed during the Activities of Daily Living assessment, performance
      on lower limber tests, and peripheral muscle impairment of the upper limb in
      patients with chronic obstructive pulmonary disease. MATERIALS AND METHODS: Ten
      men (aged 58 to 80 years old) with moderate to very severe obstruction were
      evaluated and classified by the BODE Index. They were evaluated by pulmonary
      ventilation (VE), oxygen consumption (VO2), and carbonic gas production (VCO2) on
      the ADL assessment; Distance Walking (DW) in the Six Minute Walking Test (6MWT)
      and the Six Minute Walking Test on Treadmill (6MWTT); number of repetitions in
      the Sit-to-Stand Test; and the Hand Grip Strength Test. Correlations were
      evaluated between the classification and the tests performed (Pearson and
      Spearman test, p<0.05). RESULTS: The mean of the total score for the BODE Index
      was 2.80 (+/-1.03), with three patients scoring in the first quartile (Q1) and
      seven scoring in the second quartile (Q2). This Index showed a negative
      correlation with the 6MWTT (r=-0.86), the Sit-to-Stand Test (r=-0.66), and the
      Hand Grip Strength Test (r=-0.83). CONCLUSIONS: Our results show that there is no
      correlation between the BODE Index and the ventilatory and metabolic responses in
      the Activities of Daily Living assessment. On the other hand, a correlation was
      observed between the BODE Index and the variables assessed in the 6MWTT, Sit-to
      Stand Test, and Hand Grip Strength Test in moderate to very severe Chronic
      Obstructive Pulmonary Disease patients. This suggests that these tests can be
      employed as predictors of physical exercise capacity, perhaps as complementary
      tests to the BODE Index.

PMID- 19841706
TI  - Internal jugular vein cannulation: an ultrasound-guided technique versus a
      landmark-guided technique.
AB  - OBJECTIVES: To compare the landmark-guided technique versus the ultrasound-guided
      technique for internal jugular vein cannulation in spontaneously breathing
      patients. METHODS: A total of 380 patients who required internal jugular vein
      cannulation were randomly assigned to receive internal jugular vein cannulation
      using either the landmark- or ultrasound-guided technique in Bursa, Uludag
      University Faculty of Medicine, between April and November, 2008. Failed catheter
      placement, risk of complications from placement, risk of failure on first attempt
      at placement, number of attempts until successful catheterization, time to
      successful catheterization and the demographics of each patient were recorded.
      RESULTS: The overall complication rate was higher in the landmark group than in
      the ultrasound-guided group (p < 0.01). Carotid puncture rate and hematoma were
      more frequent in the landmark group than in the ultrasound-guided group (p <
      0.05). The number of attempts for successful placement was significantly higher
      in the landmark group than in the ultrasound-guided group, which was accompanied
      by a significantly increased access time observed in the landmark group (p < 0.05
      and p < 0.01, respectively). Although there were a higher number of attempts,
      longer access time, and a more frequent complication rate in the landmark group,
      the success rate was found to be comparable between the two groups. CONCLUSION:
      The findings of this study indicate that internal jugular vein catheterization
      guided by real-time ultrasound results in a lower access time and a lower rate of
      immediate complications.

PMID- 19841707
TI  - Petroleum ether extract of Cissus quadrangularis (Linn.) enhances bone marrow
      mesenchymal stem cell proliferation and facilitates osteoblastogenesis.
AB  - OBJECTIVE: To evaluate the effects of the petroleum ether extract of Cissus
      quadrangularis on the proliferation rate of bone marrow mesenchymal stem cells,
      the differentiation of marrow mesenchymal stem cells into osteoblasts
      (osteoblastogenesis) and extracellular matrix calcification. This study also
      aimed to determine the additive effect of osteogenic media and Cissus
      quadrangularis on proliferation, differentiation and calcification. METHODS: MSCs
      were cultured in media with or without Cissus quadrangularis for 4 weeks and were
      then stained for alkaline phosphatase. Extracellular matrix calcification was
      confirmed by Von Kossa staining. marrow mesenchymal stem cells cultures in
      control media and osteogenic media supplemented with Cissus quadrangularis
      extract (100, 200, 300 microg/mL) were also subjected to a cell proliferation
      assay (MTT). RESULTS: Treatment with 100, 200 or 300 microg/mL petroleum ether
      extract of Cissus quadrangularis enhanced the differentiation of marrow
      mesenchymal stem cells into ALP-positive osteoblasts and increased extracellular
      matrix calcification. Treatment with 300 microg/mL petroleum ether extract of
      Cissus quadrangularis also enhanced the proliferation rate of the marrow
      mesenchymal stem cells. Cells grown in osteogenic media containing Cissus
      quadrangularis exhibited higher proliferation, differentiation and calcification
      rates than did control cells. CONCLUSION: The results suggest that Cissus
      quadrangularis stimulates osteoblastogenesis and can be used as preventive/
      alternative natural medicine for bone diseases such as osteoporosis.

PMID- 19841708
TI  - Mortality in anesthesia: a systematic review.
AB  - This systematic review of the Brazilian and worldwide literature aims to evaluate
      the incidence and causes of perioperative and anesthesia-related mortality.
      Studies were identified by searching the Medline and Scielo databases, followed
      by a manual search for relevant articles. Our review includes studies published
      between 1954 and 2007. Each publication was reviewed to identify author(s), study
      period, data source, perioperative mortality rates, and anesthesia-related
      mortality rates. Thirty-three trials were assessed. Brazilian and worldwide
      studies demonstrated a similar decline in anesthesia-related mortality rates,
      which amounted to fewer than 1 death per 10,000 anesthetics in the past two
      decades. Perioperative mortality rates also decreased during this period, with
      fewer than 20 deaths per 10,000 anesthetics in developed countries. Brazilian
      studies showed higher perioperative mortality rates, from 19 to 51 deaths per
      10,000 anesthetics. The majority of perioperative deaths occurred in neonates,
      children under one year, elderly patients, males, patients of ASA III physical
      status or poorer, emergency surgeries, during general anesthesia, and cardiac
      surgery followed by thoracic, vascular, gastroenterologic, pediatric and
      orthopedic surgeries. The main causes of anesthesia-related mortality were
      problems with airway management and cardiocirculatory events related to
      anesthesia and drug administration. Our systematic review of the literature shows
      that perioperative mortality rates are higher in Brazil than in developed
      countries, while anesthesia-related mortality rates are similar in Brazil and in
      developed countries. Most cases of anesthesia-related mortality are associated
      with cardiocirculatory and airway events. These data may be useful in developing
      strategies to prevent anesthesia-related deaths.

PMID- 19841709
TI  - Recent trends in Brazilian medical research. An overview.
AB  - This article reviews 69 original research articles published in 6 Brazilian
      Medical Journals recently incorporated into the Institute for Scientific
      Information Journal of Citation Reports, with a view of making them
      comprehensively available to the readership of CLINICS within a subject category
      division. We expect this review to increase the visibility of a wide specter of
      original Brazilian research which may otherwise remain relatively unseen by the
      interested readership.

PMID- 19841710
TI  - Guidelines on management of human infection with the novel virus influenza A
      (H1N1)--a report from the Hospital das Clinicas of the University of Sao Paulo.
AB  - The pandemic novel influenza A (H1N1) infection was considered widespread in
      Brazil on July, 2009. Since then, 9.249 cases were confirmed in Brazil, most of
      them concentrated in Sao Paulo. The Hospital das Clinicas of the University of
      Sao Paulo is a reference center for H1N1 cases in Sao Paulo. The purpose of this
      review is to analyze the evidence concerning diagnosis, prevention, and treatment
      of novel influenza A (H1N1) infection. In addition, we propose guidelines for the
      management of this pandemic emphasizing Hospital das Clinicas "bundles" for the
      control of the pandemic novel influenza A (H1N1).

PMID- 19841711
TI  - Epidemiology of human infection with the novel virus influenza A (H1N1) in the
      Hospital das Clinicas, Sao Paulo, Brazil--June-September 2009.
AB  - The pandemic novel influenza A (H1N1) infection was considered widespread in
      Brazil on July 16, 2009. Since then, 46,810 cases of acute respiratory syndrome
      have been reported in Brazil, most of them concentrated in Sao Paulo. Through
      September 16, we have confirmed 9,249 cases of novel influenza A H1N1in Brazil,
      including 699 deaths. The mortality rate observed in Brazil is 0.47/100,000
      inhabitants and varies according to region. In this period, Sao Paulo registered
      3733 cases (40.3% of the total) of novel influenza A (H1N1) infection and 327
      deaths, reflecting a mortality rate of 0.79/100,000 inhabitants. The Hospital das
      Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC) is a
      reference center for H1N1 cases in Sao Paulo. During the winter of 2009, 472
      patients in this hospital were diagnosed with H1N1 infection; of these, 210 were
      admitted, and 16 died. To control this pandemic and to provide adequate care for
      these patients, the Hospital das Clinicas implemented "bundles" including
      prevention strategies, an epidemiologic surveillance service, availability of
      fast diagnosis, antiviral treatment and training of staff. The purpose of this
      manuscript is to describe the epidemiologic features of novel human influenza A
      (H1N1) infection in the Hospital das Clinicas da Faculdade de Medicina da
      Universidade de Sao Paulo during the winter period of the 2009 pandemic.

PMID- 19841712
TI  - Fatal bronchovascular fistula after a single lung transplantation: a case report.

PMID- 19841713
TI  - Occipito-vertebral dissociation in connection with extensive cervical spine
      malsegmentation in a boy with Mobius syndrome.

PMID- 19841714
TI  - Oral intraneural perineurioma. Report of two cases.

PMID- 19841716
TI  - Recent synthetic studies leading to structural revisions of marine natural
      products.
AB  - Because of the highly unique structures of marine natural products, there are
      many examples of structures that were originally proposed based on spectral
      analyses but later proven incorrect. In many cases, the total syntheses of the
      originally proposed structures of marine natural products has confirmed their
      incorrectness and the subsequent total syntheses of the newly proposed structures
      proved the revised structures. This review will show such cases appearing after
      2005 and demonstrate how the true structures were elucidated.

PMID- 19841715
TI  - Phage therapy and photodynamic therapy: low environmental impact approaches to
      inactivate microorganisms in fish farming plants.
AB  - Owing to the increasing importance of aquaculture to compensate for the
      progressive worldwide reduction of natural fish and to the fact that several fish
      farming plants often suffer from heavy financial losses due to the development of
      infections caused by microbial pathogens, including multidrug resistant bacteria,
      more environmentally-friendly strategies to control fish infections are urgently
      needed to make the aquaculture industry more sustainable. The aim of this review
      is to briefly present the typical fish farming diseases and their threats and
      discuss the present state of chemotherapy to inactivate microorganisms in fish
      farming plants as well as to examine the new environmentally friendly approaches
      to control fish infection namely phage therapy and photodynamic antimicrobial
      therapy.

PMID- 19841717
TI  - The use of positron emission tomography in soft tissue sarcoma patients under
      therapy with trabectedin.
AB  - BACKGROUND: We used 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG) positron emission
      tomography (PET) to evaluate the FDG uptake in patients with advanced and/or
      metastatic soft tissue sarcoma (STS) undergoing therapy with Ecteinascidin-743
      (ET-743, Trabectedin, Yondelis). PATIENTS AND METHODS: The pilot study included
      nine patients with metastatic STS receiving a minimum of one cycle of treatment
      with trabectedin. Patients were examined using PET prior to onset of therapy and
      after completion of one or three cycles of trabectedin. Restaging according to
      Response Evaluation Criteria in Solid Tumours (RECIST) was performed in parallel
      using computed tomography (CT) and/or magnetic resonance imaging (MRI) and served
      for reference. RESULTS: clinical outcome of nine evaluable patients was as
      follows: one patient with partial remission (PR), three patients with stable
      disease (SD), and five patients with progressive disease (PD). A more than 40%
      decrease of the standardized uptake value (SUV) of sequential PET examination
      could be demonstrated for the responding patient (PR), whereas patients with SD
      or PD showed a stable SUV, but no increase in SUV. CONCLUSION: To our knowledge,
      this is the first small series of patients being treated with trabectedin and
      monitored using sequential PET imaging demonstrating SUV stabilization in nearly
      all monitored patients.

PMID- 19841718
TI  - A marine sulfate-reducing bacterium producing multiple antibiotics: biological
      and chemical investigation.
AB  - A marine sulfate-reducing bacterium SRB-22 was isolated by means of the agar
      shake dilution method and identified as Desulfovibrio desulfuricans by
      morphological, physiological and biochemical characteristics and 16S rDNA
      analysis. In the bioassay, its extract showed broad-spectrum antimicrobial
      activity using the paper disc agar diffusion method. This isolate showed a
      different antimicrobial profile than either ampicillin or nystatin and was found
      to produce at least eight antimicrobial components by bioautography. Suitable
      fermentation conditions for production of the active constituents were determined
      to be 28 day cultivation at 25 degrees C to 30 degrees C with a 10% inoculation
      ratio. Under these conditions, the SRB-22 was fermented, extracted and chemically
      investigated. So far an antimicrobial compound, mono-n-butyl phthalate, and an
      inactive compound, thymine, have been isolated and characterized.

PMID- 19841719
TI  - Brominated selinane sesquiterpenes from the marine brown alga Dictyopteris
      divaricata.
AB  - Two new brominated selinane sesquiterpenes, 1-bromoselin-4(14),11-diene (1) and 9
      bromoselin-4(14),11-diene (2), one known cadinane sesquiterpene, cadalene (3),
      and four known selinane sesquiterpenes, alpha-selinene (4), beta-selinene (5),
      beta-dictyopterol (6), and cyperusol C (7), were isolated from a sample of marine
      brown alga Dictyopteris divaricata collected off the coast of Yantai (China).
      Their structures were established by detailed MS and NMR spectroscopic analysis,
      as well as comparison with literature data.

PMID- 19841720
TI  - The Mediterranean red alga Asparagopsis: a source of compounds against
      Leishmania.
AB  - Crude extracts and column fractions from the red algae Asparagopsis taxiformis
      and A. armata from the Strait of Messina (Italy) were screened for the production
      of antimicrobial compounds. Extracts from both species revealed remarkable
      antiprotozoal activity against Leishmania, revealing such algae as a great source
      of natural antiprotozoal products.

PMID- 19841721
TI  - The influence of bioactive oxylipins from marine diatoms on invertebrate
      reproduction and development.
AB  - Diatoms are one of the main primary producers in aquatic ecosystems and occupy a
      vital link in the transfer of photosynthetically-fixed carbon through aquatic
      food webs. Diatoms produce an array of biologically-active metabolites, many of
      which have been attributed as a form of chemical defence and may offer potential
      as candidate marine drugs. Of considerable interest are molecules belonging to
      the oxylipin family which are broadly disruptive to reproductive and
      developmental processes. The range of reproductive impacts includes; oocyte
      maturation; sperm motility; fertilization; embryogenesis and larval competence.
      Much of the observed bioactivity may be ascribed to disruption of intracellular
      calcium signalling, induction of cytoskeletal instability and promotion of
      apoptotic pathways. From an ecological perspective, the primary interest in
      diatom-oxylipins is in relation to the potential impact on energy flow in
      planktonic systems whereby the reproductive success of copepods (the main grazers
      of diatoms) is compromised. Much data exists providing evidence for and against
      diatom reproductive effects; however detailed knowledge of the physiological and
      molecular processes involved remains poor. This paper provides a review of the
      current state of knowledge of the mechanistic impacts of diatom-oxylipins on
      marine invertebrate reproduction and development.

PMID- 19841723
TI  - Two new jaspamide derivatives from the marine sponge Jaspis splendens.
AB  - Two new jaspamide derivatives 2 and 3, together with the parent compound
      jaspamide (1) have been isolated from the marine sponge Jaspis splendens
      collected in Kalimantan (Indonesia). The structures of the new compounds were
      unambiguously elucidated based on 1D and 2D NMR spectral data, mass spectrometry
      and comparison with jaspamide (1). The new derivatives inhibited the growth of
      mouse lymphoma (L5178Y) cell line in vitro with IC(50) values of <0.1 microg/mL.

PMID- 19841722
TI  - Marine-derived metabolites of S-adenosylmethionine as templates for new anti
      infectives.
AB  - S-Adenosylmethionine (AdoMet) is a key biochemical co-factor whose proximate
      metabolites include methylated macromolecules (e.g., nucleic acids, proteins,
      phospholipids), methylated small molecules (e.g., sterols, biogenic amines),
      polyamines (e.g., spermidine, spermine), ethylene, and N-acyl-homoserine
      lactones. Marine organisms produce numerous AdoMet metabolites whose novel
      structures can be regarded as lead compounds for anti-infective drug design.

PMID- 19841724
TI  - 1,5-diazacyclohenicosane, a new cytotoxic metabolite from the marine sponge
      Mycale sp.
AB  - A new cyclic diamine, 1,5-diazacyclohenicosane (1), was isolated from samples of
      the marine sponge Mycale sp. collected at Lamu Island (Kenya). Its structure was
      determined by a combination of spectroscopic techniques, including (+)-HRESIMS
      and 1D and 2D NMR spectroscopy. The compound displayed cytotoxicity at the muM
      level against three human tumor cell lines.

PMID- 19841725
TI  - Phase II study of biweekly plitidepsin as second-line therapy for advanced or
      metastatic transitional cell carcinoma of the urothelium.
AB  - The objective of this exploratory, open-label, single-arm, phase II clinical
      trial was to evaluate plitidepsin (5 mg/m(2)) administered as a 3-hour continuous
      intravenous infusion every two weeks to patients with locally advanced/metastatic
      transitional cell carcinoma of the urothelium who relapsed/progressed after first
      line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until
      disease progression, unacceptable toxicity, patient refusal or treatment delay
      for >2 weeks. The primary efficacy endpoint was objective response rate according
      to RECIST. Secondary endpoints were the rate of SD lasting > or = 6 months and
      time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one
      patients received 57 treatment cycles. No objective tumor responses occurred. SD
      lasting <6 months was observed in two of 18 evaluable patients. With a median
      follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3
      months, respectively. The most common AEs were mild to moderate nausea, fatigue,
      myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases,
      alkaline phosphatase and creatinine were the most frequent laboratory
      abnormalities. No severe neutropenia occurred. Treatment was feasible and
      generally well tolerated in this patient population; however the lack of
      antitumor activity precludes further studies of plitidepsin in this setting.

PMID- 19841726
TI  - Antibacterial activity of 2-(2',4'-dibromophenoxy)-4,6-dibromophenol from Dysidea
      granulosa.
AB  - 2-(2',4'-Dibromophenoxy)-4,6-dibromophenol isolated from the marine sponge
      Dysidea granulosa (Bergquist) collected off the coast of Lakshadweep islands,
      Indian Ocean, exhibited potent and broad spectrum in-vitro antibacterial
      activity, especially against methicillin resistant Staphylococcus aureus (MRSA),
      methicillin sensitive Staphylococcus aureus (MSSA), vancomycin resistant
      Enterococci (VRE), vancomycin sensitive Enterococci (VSE) and Bacillus spp.
      Minimal inhibitory concentration (MIC) was evaluated against 57 clinical and
      standard strains of Gram positive and Gram negative bacteria. The observed MIC
      range was 0.117-2.5 microg/mL against all the Gram positive bacteria and 0.5-2
      microg/mL against Gram negative bacteria. The in-vitro antibacterial activity
      observed was better than that of the standard antibiotic linezolid, a marketed
      anti-MRSA drug. The results establish 2-(2',4'-dibromophenoxy)-4,6-dibromophenol,
      as a potential lead molecule for anti-MRSA and anti-VRE drug development.

PMID- 19841727
TI  - Excavatoids E and F: discovery of two new briaranes from the cultured octocoral
      Briareum excavatum.
AB  - Two new briarane-related diterpenoids, designated as excavatoids E (1) and F (2),
      were isolated from the cultured octocoral Briareum excavatum. The structures of
      compounds 1 and 2 were established on the basis of extensive spectral data
      analysis. Briaranes 1 and 2 were found to exhibit moderate inhibitory effects on
      elastase release by human neutrophils.

PMID- 19841729
TI  - Classification of hip joint infections.
AB  - Infections still remain one of the most devastating complications in hip joint
      surgery. Classification of these infections help the orthopaedic surgeon to
      identify the acuteness or chronicity of the infection, predict the complexity of
      the treatment procedure and ensure that all necessary device are available at the
      time of the revision surgery. The present article reviews the actual literature
      and provides an overview of clinical, arthroscopic, microbiological and
      radiological staging systems.

PMID- 19841728
TI  - Differentiation driven changes in the dynamic organization of Basal transcription
      initiation.
AB  - Studies based on cell-free systems and on in vitro-cultured living cells support
      the concept that many cellular processes, such as transcription initiation, are
      highly dynamic: individual proteins stochastically bind to their substrates and
      disassemble after reaction completion. This dynamic nature allows quick
      adaptation of transcription to changing conditions. However, it is unknown to
      what extent this dynamic transcription organization holds for postmitotic cells
      embedded in mammalian tissue. To allow analysis of transcription initiation
      dynamics directly into living mammalian tissues, we created a knock-in mouse
      model expressing fluorescently tagged TFIIH. Surprisingly and in contrast to what
      has been observed in cultured and proliferating cells, postmitotic murine cells
      embedded in their tissue exhibit a strong and long-lasting transcription
      dependent immobilization of TFIIH. This immobilization is both differentiation
      driven and development dependent. Furthermore, although very statically bound,
      TFIIH can be remobilized to respond to new transcriptional needs. This divergent
      spatiotemporal transcriptional organization in different cells of the soma
      revisits the generally accepted highly dynamic concept of the kinetic framework
      of transcription and shows how basic processes, such as transcription, can be
      organized in a fundamentally different fashion in intact organisms as previously
      deduced from in vitro studies.

PMID- 19841730
TI  - Treatment of proximal femur infections with antibiotic-loaded cement spacers.
AB  - In case of periprosthetic hip infections the implantation of antibiotic-loaded
      PMMA spacers is accepted for an adequate treatment option. Although their
      indication for the treatment of destructive, bacterial infections of the proximal
      femur would make sense, literature data are scarce. Hence, the aim of this study
      was to evaluate the efficacy of antibiotic-impregnated spacers in the treatment
      of proximal femur infections. In 10 consecutive patients (5 M/ 5 F, mean age 66
      y.) with bacterial proximal femur infections, a femoral head/neck resection was
      prospectively performed with a subsequent implantation of an antibiotic-loaded
      spacer. The joint-specific outcome was evaluated by the Merle d'Aubigne and the
      Mayo hip score, the general outcome by SF-36. The time periods were divided into
      "infection situation", "between stages" and meanly 1 year "after prosthesis
      implantation". The spacers were meanly implanted over 90 [155-744] days. In all
      cases an infection eradication could be achieved. After infection eradication, a
      prosthesis implantation was performed in 8 cases. The general scores showed
      significant increases at each time period. With regard to the dimension "pain",
      both scores demonstrated a significant increase between "infection situation" and
      "between stages", but no significance between "between stages" and "after
      prosthesis implantation". Spacers could be indicated in the treatment of proximal
      femur infections. Besides an infection eradication, a pain reduction is also
      possible.

PMID- 19841731
TI  - Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal
      dynamics of endocytosis proteins.
AB  - SH3 domains are peptide recognition modules that mediate the assembly of diverse
      biological complexes. We scanned billions of phage-displayed peptides to map the
      binding specificities of the SH3 domain family in the budding yeast,
      Saccharomyces cerevisiae. Although most of the SH3 domains fall into the
      canonical classes I and II, each domain utilizes distinct features of its cognate
      ligands to achieve binding selectivity. Furthermore, we uncovered several SH3
      domains with specificity profiles that clearly deviate from the two canonical
      classes. In conjunction with phage display, we used yeast two-hybrid and peptide
      array screening to independently identify SH3 domain binding partners. The
      results from the three complementary techniques were integrated using a Bayesian
      algorithm to generate a high-confidence yeast SH3 domain interaction map. The
      interaction map was enriched for proteins involved in endocytosis, revealing a
      set of SH3-mediated interactions that underlie formation of protein complexes
      essential to this biological pathway. We used the SH3 domain interaction network
      to predict the dynamic localization of several previously uncharacterized
      endocytic proteins, and our analysis suggests a novel role for the SH3 domains of
      Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes.

PMID- 19841732
TI  - Daughter-specific transcription factors regulate cell size control in budding
      yeast.
AB  - In budding yeast, asymmetric cell division yields a larger mother and a smaller
      daughter cell, which transcribe different genes due to the daughter-specific
      transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint
      has long been considered to be a main regulator of the length of the G1 phase of
      the cell cycle, resulting in longer G1 in the smaller daughter cells. Our recent
      data confirmed this concept using quantitative time-lapse microscopy. However, it
      has been proposed that daughter-specific, Ace2-dependent repression of expression
      of the G1 cyclin CLN3 had a dominant role in delaying daughters in G1. We wanted
      to reconcile these two divergent perspectives on the origin of long daughter G1
      times. We quantified size control using single-cell time-lapse imaging of
      fluorescently labeled budding yeast, in the presence or absence of the daughter
      specific transcriptional regulators Ace2 and Ash1. Ace2 and Ash1 are not required
      for efficient size control, but they shift the domain of efficient size control
      to larger cell size, thus increasing cell size requirement for Start in
      daughters. Microarray and chromatin immunoprecipitation experiments show that
      Ace2 and Ash1 are direct transcriptional regulators of the G1 cyclin gene CLN3.
      Quantification of cell size control in cells expressing titrated levels of Cln3
      from ectopic promoters, and from cells with mutated Ace2 and Ash1 sites in the
      CLN3 promoter, showed that regulation of CLN3 expression by Ace2 and Ash1 can
      account for the differential regulation of Start in response to cell size in
      mothers and daughters. We show how daughter-specific transcriptional programs can
      interact with intrinsic cell size control to differentially regulate Start in
      mother and daughter cells. This work demonstrates mechanistically how asymmetric
      localization of cell fate determinants results in cell-type-specific regulation
      of the cell cycle.

PMID- 19841734
TI  - Sex determination in honeybees: two separate mechanisms induce and maintain the
      female pathway.
AB  - Organisms have evolved a bewildering diversity of mechanisms to generate the two
      sexes. The honeybee (Apis mellifera) employs an interesting system in which sex
      is determined by heterozygosity at a single locus (the Sex Determination Locus)
      harbouring the complementary sex determiner (csd) gene. Bees heterozygous at Sex
      Determination Locus are females, whereas bees homozygous or hemizygous are males.
      Little is known, however, about the regulation that links sex determination to
      sexual differentiation. To investigate the control of sexual development in
      honeybees, we analyzed the functions and the regulatory interactions of genes
      involved in the sex determination pathway. We show that heterozygous csd is only
      required to induce the female pathway, while the feminizer (fem) gene maintains
      this decision throughout development. By RNAi induced knockdown we show that the
      fem gene is essential for entire female development and that the csd gene
      exclusively processes the heterozygous state. Fem activity is also required to
      maintain the female determined pathway throughout development, which we show by
      mosaic structures in fem-repressed intersexuals. We use expression of Fem protein
      in males to demonstrate that the female maintenance mechanism is controlled by a
      positive feedback splicing loop in which Fem proteins mediate their own synthesis
      by directing female fem mRNA splicing. The csd gene is only necessary to induce
      this positive feedback loop in early embryogenesis by directing splicing of fem
      mRNAs. Finally, fem also controls the splicing of Am-doublesex transcripts
      encoding conserved male- and female-specific transcription factors involved in
      sexual differentiation. Our findings reveal how the sex determination process is
      realized in honeybees differing from Drosophila melanogaster.

PMID- 19841733
TI  - Kruppel-like family of transcription factors: an emerging new frontier in fat
      biology.
AB  - In mammals, adipose tissue stores energy in the form of fat. The ability to
      regulate fat storage is essential for the growth, development and reproduction of
      most animals, thus any abnormalities caused by excess fat accumulation can result
      in pathological conditions which are linked to several interrelated diseases,
      such as cardiovascular diseases, diabetes, and obesity. In recent years
      significant effort has been applied to understand basic mechanism of fat
      accumulation in mammalian system. Work in mouse has shown that the family of
      Kruppel-like factors (KLFs), a conserved and important class of transcription
      factors, regulates adipocyte differentiation in mammals. However, how fat storage
      is coordinated in response to positive and negative feedback signals is still
      poorly understood. To address mechanisms underlying fat storage we have studied
      two Caenorhabditis elegans KLFs and demonstrate that both worm klfs are key
      regulators of fat metabolism in C. elegans. These results provide the first in
      vivo evidence supporting essential regulatory roles for KLFs in fat metabolism in
      C. elegans and shed light on the human counterpart in disease-gene association.
      This finding allows us to pursue a more comprehensive approach to understand fat
      biology and provides an opportunity to learn about the cascade of events that
      regulate KLF activation, repression and interaction with other factors in
      exerting its biological function at an organismal level. In this review, we
      provide an overview of the most current information on the key regulatory
      components in fat biology, synthesize the diverse literature, pose new questions,
      and propose a new model organism for understanding fat biology using KLFs as the
      central theme.

PMID- 19841735
TI  - Packages of care for schizophrenia in low- and middle-income countries.

PMID- 19841736
TI  - Inaccuracy of enzyme-linked immunosorbent assay using soluble and recombinant
      antigens to detect asymptomatic infection by Leishmania infantum.
AB  - BACKGROUND: One of the most important drawbacks in visceral leishmaniasis (VL)
      population studies is the difficulty of diagnosing asymptomatic carriers. The aim
      of this study, conducted in an urban area in the Southeast of Brazil, was to
      evaluate the performance of serology to identify asymptomatic VL infection in
      participants selected from a cohort with a two-year follow-up period.
      METHODOLOGY: Blood samples were collected in 2001 from 136 cohort participants
      (97 positive and 39 negatives, PCR/hybridization carried out in 1999). They were
      clinically evaluated and none had progressed to disease from their asymptomatic
      state. As controls, blood samples from 22 control individuals and 8 patients with
      kala-azar were collected. Two molecular biology techniques (reference tests) were
      performed: PCR with Leishmania-generic primer followed by hybridization using L.
      infantum probe, and PCR with specific primer to L. donovani complex. Plasma
      samples were tested by ELISA using three different antigens: L. infantum and L.
      amazonensis crude antigens, and rK39 recombinant protein. Accuracy of the
      serological tests was evaluated using sensitivity, specificity, likelihood ratio
      and ROC curve. FINDINGS: The presence of Leishmania was confirmed, by molecular
      techniques, in all kala-azar patients and in 117 (86%) of the 136 cohort
      participants. Kala-azar patients showed high reactivity in ELISAs, whereas
      asymptomatic individuals presented low reactivity against the antigens tested.
      When compared to molecular techniques, the L. amazonensis and L. infantum
      antigens showed higher sensitivity (49.6% and 41.0%, respectively) than rK39
      (26.5%); however, the specificity of rK39 was higher (73.7%) than L. amazonensis
      (52.6%) and L. infantum antigens (36.8%). Moreover, there was low agreement among
      the different antigens used (kappa<0.10). CONCLUSIONS: Serological tests were
      inaccurate for diagnosing asymptomatic infections compared to molecular methods;
      this could lead to misclassification bias in population studies. Therefore,
      studies which have used serological assays to estimate prevalence, to evaluate
      intervention programs or to identify risk factors for Leishmania infection, may
      have had their results compromised.

PMID- 19841737
TI  - Nicotine promotes tumor growth and metastasis in mouse models of lung cancer.
AB  - BACKGROUND: Nicotine is the major addictive component of tobacco smoke. Although
      nicotine is generally thought to have limited ability to initiate cancer, it can
      induce cell proliferation and angiogenesis in a variety of systems. These
      properties might enable nicotine to facilitate the growth of tumors already
      initiated. Here we show that nicotine significantly promotes the progression and
      metastasis of tumors in mouse models of lung cancer. This effect was observed
      when nicotine was administered through intraperitoneal injections, or through
      over-the-counter transdermal patches. METHODS AND FINDINGS: In the present study,
      Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic
      BALB/c mice. Nicotine administration either by intraperitoneal (i.p.) injection
      or transdermal patches caused a remarkable increase in the size of implanted
      Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had
      a markedly higher tumor recurrence (59.7%) as compared to the vehicle treated
      mice (19.5%). Nicotine also increased metastasis of dorsally implanted Line1
      tumors to the lungs by 9 folds. These studies on transplanted tumors were
      extended to a mouse model where the tumors were induced by the tobacco
      carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK;
      administration of 1 mg/kg nicotine three times a week led to an increase in the
      size and the number of tumors formed in the lungs. In addition, nicotine
      significantly reduced the expression of epithelial markers, E-Cadherin and beta
      Catenin as well as the tight junction protein ZO-1; these tumors also showed an
      increased expression of the alpha(7) nAChR subunit. We believe that exposure to
      nicotine either by tobacco smoke or nicotine supplements might facilitate
      increased tumor growth and metastasis. CONCLUSIONS: Our earlier results indicated
      that nicotine could induce invasion and epithelial-mesenchymal transition (EMT)
      in cultured lung, breast and pancreatic cancer cells. This study demonstrates for
      the first time that administration of nicotine either by i.p. injection or
      through over-the-counter dermal patches can promote tumor growth and metastasis
      in immunocompetent mice. These results suggest that while nicotine has only
      limited capacity to initiate tumor formation, it can facilitate the progression
      and metastasis of tumors pre-initiated by tobacco carcinogens.

PMID- 19841738
TI  - Identification of a PA-binding peptide with inhibitory activity against influenza
      A and B virus replication.
AB  - There is an urgent need for new drugs against influenza type A and B viruses due
      to incomplete protection by vaccines and the emergence of resistance to current
      antivirals. The influenza virus polymerase complex, consisting of the PB1, PB2
      and PA subunits, represents a promising target for the development of new drugs.
      We have previously demonstrated the feasibility of targeting the protein-protein
      interaction domain between the PB1 and PA subunits of the polymerase complex of
      influenza A virus using a small peptide derived from the PA-binding domain of
      PB1. However, this influenza A virus-derived peptide did not affect influenza B
      virus polymerase activity. Here we report that the PA-binding domain of the
      polymerase subunit PB1 of influenza A and B viruses is highly conserved and that
      mutual amino acid exchange shows that they cannot be functionally exchanged with
      each other. Based on phylogenetic analysis and a novel biochemical ELISA-based
      screening approach, we were able to identify an influenza A-derived peptide with
      a single influenza B-specific amino acid substitution which efficiently binds to
      PA of both virus types. This dual-binding peptide blocked the viral polymerase
      activity and growth of both virus types. Our findings provide proof of principle
      that protein-protein interaction inhibitors can be generated against influenza A
      and B viruses. Furthermore, this dual-binding peptide, combined with our novel
      screening method, is a promising platform to identify new antiviral lead
      compounds.

PMID- 19841739
TI  - Imatinib and nilotinib reverse multidrug resistance in cancer cells by inhibiting
      the efflux activity of the MRP7 (ABCC10).
AB  - BACKGROUND: One of the major mechanisms that could produce resistance to
      antineoplastic drugs in cancer cells is the ATP binding cassette (ABC)
      transporters. The ABC transporters can significantly decrease the intracellular
      concentration of antineoplastic drugs by increasing their efflux, thereby
      lowering the cytotoxic activity of antineoplastic drugs. One of these
      transporters, the multiple resistant protein 7 (MRP7, ABCC10), has recently been
      shown to produce resistance to antineoplastic drugs by increasing the efflux of
      paclitaxel. In this study, we examined the effects of BCR-Abl tyrosine kinase
      inhibitors imatinib, nilotinib and dasatinib on the activity and expression of
      MRP7 in HEK293 cells transfected with MRP7, designated HEK-MRP7-2. METHODOLOGY
      AND/OR PRINCIPAL FINDINGS: We report for the first time that imatinib and
      nilotinib reversed MRP7-mediated multidrug resistance. Our MTT assay results
      indicated that MRP7 expression in HEK-MRP7-2 cells was not significantly altered
      by incubation with 5 microM of imatinib or nilotinib for up to 72 hours. In
      addition, imatinib and nilotinib (1-5 microM) produced a significant
      concentration-dependent reversal of MRP7-mediated multidrug resistance by
      enhancing the sensitivity of HEK-MRP7-2 cells to paclitaxel and vincristine.
      Imatinib and nilotinib, at 5 microM, significantly increased the accumulation of
      [(3)H]-paclitaxel in HEK-MRP7-2 cells. The incubation of the HEK-MRP7-2 cells
      with imatinib or nilotinib (5 microM) also significantly inhibited the efflux of
      paclitaxel. CONCLUSIONS: Imatinib and nilotinib reverse MRP7-mediated paclitaxel
      resistance, most likely due to their inhibition of the efflux of paclitaxel via
      MRP7. These findings suggest that imatinib or nilotinib, in combination with
      other antineoplastic drugs, may be useful in the treatment of certain resistant
      cancers.

PMID- 19841740
TI  - Influenza A gradual and epochal evolution: insights from simple models.
AB  - The recurrence of influenza A epidemics has originally been explained by a
      "continuous antigenic drift" scenario. Recently, it has been shown that if
      genetic drift is gradual, the evolution of influenza A main antigen, the
      haemagglutinin, is punctuated. As a consequence, it has been suggested that
      influenza A dynamics at the population level should be approximated by a serial
      model. Here, simple models are used to test whether a serial model requires
      gradual antigenic drift within groups of strains with the same antigenic
      properties (antigenic clusters). We compare the effect of status based and
      history based frameworks and the influence of reduced susceptibility and
      infectivity assumptions on the transient dynamics of antigenic clusters. Our
      results reveal that the replacement of a resident antigenic cluster by a mutant
      cluster, as observed in data, is reproduced only by the status based model
      integrating the reduced infectivity assumption. This combination of assumptions
      is useful to overcome the otherwise extremely high model dimensionality of models
      incorporating many strains, but relies on a biological hypothesis not obviously
      satisfied. Our findings finally suggest the dynamical importance of gradual
      antigenic drift even in the presence of punctuated immune escape. A more regular
      renewal of susceptible pool than the one implemented in a serial model should be
      part of a minimal theory for influenza at the population level.

PMID- 19841741
TI  - Balancing with vibration: a prelude for "drift and act" balance control.
AB  - Stick balancing at the fingertip is a powerful paradigm for the study of the
      control of human balance. Here we show that the mean stick balancing time is
      increased by about two-fold when a subject stands on a vibrating platform that
      produces vertical vibrations at the fingertip (0.001 m, 15-50 Hz). High speed
      motion capture measurements in three dimensions demonstrate that vibration does
      not shorten the neural latency for stick balancing or change the distribution of
      the changes in speed made by the fingertip during stick balancing, but does
      decrease the amplitude of the fluctuations in the relative positions of the
      fingertip and the tip of the stick in the horizontal plane, A(x,y). The findings
      are interpreted in terms of a time-delayed "drift and act" control mechanism in
      which controlling movements are made only when controlled variables exceed a
      threshold, i.e. the stick survival time measures the time to cross a threshold.
      The amplitude of the oscillations produced by this mechanism can be decreased by
      parametric excitation. It is shown that a plot of the logarithm of the vibration
      induced increase in stick balancing skill, a measure of the mean first passage
      time, versus the standard deviation of the A(x,y) fluctuations, a measure of the
      distance to the threshold, is linear as expected for the times to cross a
      threshold in a stochastic dynamical system. These observations suggest that the
      balanced state represents a complex time-dependent state which is situated in a
      basin of attraction that is of the same order of size. The fact that vibration
      amplitude can benefit balance control raises the possibility of minimizing risk
      of falling through appropriate changes in the design of footwear and roughness of
      the walking surfaces.

PMID- 19841743
TI  - A feeding induced switch from a variable to a homogenous state of the earthworm
      gut microbiota within a host population.
AB  - BACKGROUND: The distribution pattern of the earthworm gut microbiota at the host
      population level is of fundamental importance to understand host-microbiota
      interactions. Our current understanding of these interactions is very limited.
      Since feeding represents a main perturbation of the gut microbiota, we determined
      the effect of a single dose of feed on the microbiota associated with an
      earthworm population in a simulated microenvironment. METHODOLOGY: Earthworms
      were sampled 0, 1 and 7 days after feeding. We determined the overall composition
      of the earthworm-associated microbiota by 16S rRNA gene cloning and sequencing.
      Based on the 16S rRNA gene data we constructed quantitative PCR's (Q-PCR) for the
      seven most dominating bacterial groups. PRINCIPAL FINDINGS: Q-PCR revealed low
      density and highly variable microbiota among the earthworms before feeding, while
      a high-density homologous microbiota resulted from feeding. We found that the
      microbiota 1 day after feeding was more equal to the microbiota after 7 days than
      before feeding. Furthermore, we found that the gut microbiota was very distinct
      from that of the bedding and the feed. SIGNIFICANCE: The homogenous population
      response represents fundamental new knowledge about earthworm gut associated
      bacteria.

PMID- 19841742
TI  - BMP signaling mediates effects of exercise on hippocampal neurogenesis and
      cognition in mice.
AB  - Exposure to exercise or to environmental enrichment increases the generation of
      new neurons in the adult hippocampus and promotes certain kinds of learning and
      memory. While the precise role of neurogenesis in cognition has been debated
      intensely, comparatively few studies have addressed the mechanisms linking
      environmental exposures to cellular and behavioral outcomes. Here we show that
      bone morphogenetic protein (BMP) signaling mediates the effects of exercise on
      neurogenesis and cognition in the adult hippocampus. Elective exercise reduces
      levels of hippocampal BMP signaling before and during its promotion of
      neurogenesis and learning. Transgenic mice with decreased BMP signaling or wild
      type mice infused with a BMP inhibitor both exhibit remarkable gains in
      hippocampal cognitive performance and neurogenesis, mirroring the effects of
      exercise. Conversely, transgenic mice with increased BMP signaling have
      diminished hippocampal neurogenesis and impaired cognition. Exercise exposure
      does not rescue these deficits, suggesting that reduced BMP signaling is required
      for environmental effects on neurogenesis and learning. Together, these
      observations show that BMP signaling is a fundamental mechanism linking
      environmental exposure with changes in cognitive function and cellular properties
      in the hippocampus.

PMID- 19841744
TI  - Comprehensive gene and microRNA expression profiling reveals a role for microRNAs
      in human liver development.
AB  - BACKGROUND AND AIMS: microRNAs (miRNAs) are small noncoding RNAs that regulate
      cognate mRNAs post-transcriptionally. miRNAs have been implicated in regulating
      gene expression in embryonic developmental processes, including proliferation and
      differentiation. The liver is a multifunctional organ, which undergoes rapid
      changes during the developmental period and relies on tightly-regulated gene
      expression. Little is known regarding the complex expression patterns of both
      mRNAs and miRNAs during the early stages of human liver development, and the role
      of miRNAs in the regulation of this process has not been studied. The aim of this
      work was to study the impact of miRNAs on gene expression during early human
      liver development. METHODS: Global gene and miRNA expression were profiled in
      adult and in 9-12w human embryonic livers, using high-density microarrays and
      quantitative RT-PCR. RESULTS: Embryonic liver samples exhibited a gene expression
      profile that differentiated upon progression in the developmental process, and
      revealed multiple regulated genes. miRNA expression profiling revealed four major
      expression patterns that correlated with the known function of regulated miRNAs.
      Comparison of the expression of the most regulated miRNAs to that of their
      putative targets using a novel algorithm revealed a significant anti-correlation
      for several miRNAs, and identified the most active miRNAs in embryonic and in
      adult liver. Furthermore, our algorithm facilitated the identification of TGFbeta
      R1 as a novel target gene of let-7. CONCLUSIONS: Our results uncover multiple
      regulated miRNAs and genes throughout human liver development, and our algorithm
      assists in identification of novel miRNA targets with potential roles in liver
      development.

PMID- 19841745
TI  - Potential role of decoy B7-H4 in the pathogenesis of rheumatoid arthritis: a
      mouse model informed by clinical data.
AB  - BACKGROUND: A pathogenic hallmark of rheumatoid arthritis (RA) is persistent
      inflammatory responses in target tissues and organs. Immune responses mediated by
      T cells and autoantibodies are known to play pivotal roles. A possible
      interpretation for this observation is a loss of negative regulation of
      autoimmune responses. Here we sought to investigate whether B7-H4, a cell surface
      inhibitory molecule of the B7-CD28 signaling pathway, may play a role in the
      pathogenesis of RA. METHODS AND FINDINGS: In a cross-sectional study of a
      clinical convenience sample using monoclonal antibodies against human B7-H4
      molecules, we detected high levels of the soluble form of B7-H4 (sH4) in the sera
      of 65% of patients with RA (n = 68) versus only 13% of healthy donors (n = 24).
      Elevated sH4 was associated with an increased disease severity score (DAS28) in a
      cross-sectional analysis. In a mouse model of RA, transgenic expression of sH4 or
      genetic deletion of B7-H4 accelerated the progression of collagen-induced
      arthritis, accompanied by enhanced T and B cell-mediated autoimmune responses as
      well as increased activity of neutrophils. Expression in vivo of an agonist, a B7
      H4-immunoglobulin Fc fusion protein, profoundly suppressed disease progression in
      the mouse model. CONCLUSIONS: Our findings in mice indicate that sH4 acts as a
      decoy molecule to block the inhibitory functions of cell-surface B7-H4, leading
      to exacerbation of collagen-induced arthritis. If the preliminary correlation
      between sH4 levels and disease activity in patients with RA can be confirmed to
      reflect a similar mechanism, these findings suggest a novel target for treatment
      approaches. Please see later in the article for the Editors' Summary.

PMID- 19841746
TI  - Immunogenic salivary proteins of Triatoma infestans: development of a recombinant
      antigen for the detection of low-level infestation of triatomines.
AB  - BACKGROUND: Triatomines are vectors of Trypanosoma cruzi, the etiological agent
      of Chagas disease in Latin America. The most effective vector, Triatoma
      infestans, has been controlled successfully in much of Latin America using
      insecticide spraying. Though rarely undertaken, surveillance programs are
      necessary in order to identify new infestations and estimate the intensity of
      triatomine bug infestations in domestic and peridomestic habitats. Since hosts
      exposed to triatomines develop immune responses to salivary antigens, these
      responses can be evaluated for their usefulness as epidemiological markers to
      detect infestations of T. infestans. METHODOLOGY/PRINCIPAL FINDINGS: T. infestans
      salivary proteins were separated by 2D-gel electrophoresis and tested for their
      immunogenicity by Western blotting using sera from chickens and guinea pigs
      experimentally exposed to T. infestans. From five highly immunogenic protein
      spots, eight salivary proteins were identified by nano liquid chromatography
      electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS) and
      comparison to the protein sequences of the National Center for Biotechnology
      Information (NCBI) database and expressed sequence tags of a unidirectionally
      cloned salivary gland cDNA library from T. infestans combined with the NCBI yeast
      protein sub-database. The 14.6 kDa salivary protein [gi|149689094] was produced
      as recombinant protein (rTiSP14.6) in a mammalian cell expression system and
      recognized by all animal sera. The specificity of rTiSP14.6 was confirmed by the
      lack of reactivity to anti-mosquito and anti-sand fly saliva antibodies. However,
      rTiSP14.6 was recognized by sera from chickens exposed to four other triatomine
      species, Triatoma brasiliensis, T. sordida, Rhodnius prolixus, and Panstrongylus
      megistus and by sera of chickens from an endemic area of T. infestans and Chagas
      disease in Bolivia. CONCLUSIONS/SIGNIFICANCE: The recombinant rTiSP14.6 is a
      suitable and promising epidemiological marker for detecting the presence of small
      numbers of different species of triatomines and could be developed for use as a
      new tool in surveillance programs, especially to corroborate vector elimination
      in Chagas disease vector control campaigns.

PMID- 19841748
TI  - Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following
      Campylobacter jejuni infection.
AB  - Limited information is available on the molecular mechanisms associated with
      Campylobacter jejuni (C. jejuni) induced food-borne diarrheal illnesses. In this
      study, we investigated the function of TLR/NF-kappaB signaling in C. jejuni
      induced pathogenesis using gnotobiotic IL-10(-/-); NF-kappaB(EGFP) mice. In vitro
      analysis showed that C. jejuni induced IkappaB phosphorylation, followed by
      enhanced NF-kappaB transcriptional activity and increased IL-6, MIP-2alpha and
      NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93.
      Importantly, these events were blocked by molecular delivery of an IkappaB
      inhibitor (Ad5IkappaBAA). NF-kappaB signalling was also important for C.jejuni
      induced cytokine gene expression in bone marrow-derived dendritic cells.
      Importantly, C. jejuni associated IL-10(-/-); NF-kappaB(EGFP) mice developed mild
      (day 5) and severe (day 14) ulcerating colonic inflammation and bloody diarrhea
      as assessed by colonoscopy and histological analysis. Macroscopic analysis showed
      elevated EGFP expression indicating NF-kappaB activation throughout the colon of
      C. jejuni associated IL-10(-/-); NF-kappaB(EGFP) mice, while fluorescence
      microscopy revealed EGFP positive cells to be exclusively located in lamina
      propria mononuclear cells. Pharmacological NF-kappaB inhibition using Bay 11-7085
      did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate
      that C. jejuni induces rapid and severe intestinal inflammation in a susceptible
      host that correlates with enhanced NF-kappaB activity from lamina propria immune
      cells.

PMID- 19841749
TI  - Temporal-difference reinforcement learning with distributed representations.
AB  - Temporal-difference (TD) algorithms have been proposed as models of reinforcement
      learning (RL). We examine two issues of distributed representation in these TD
      algorithms: distributed representations of belief and distributed discounting
      factors. Distributed representation of belief allows the believed state of the
      world to distribute across sets of equivalent states. Distributed exponential
      discounting factors produce hyperbolic discounting in the behavior of the agent
      itself. We examine these issues in the context of a TD RL model in which state
      belief is distributed over a set of exponentially-discounting "micro-Agents",
      each of which has a separate discounting factor (gamma). Each microAgent
      maintains an independent hypothesis about the state of the world, and a separate
      value-estimate of taking actions within that hypothesized state. The overall
      agent thus instantiates a flexible representation of an evolving world-state. As
      with other TD models, the value-error (delta) signal within the model matches
      dopamine signals recorded from animals in standard conditioning reward-paradigms.
      The distributed representation of belief provides an explanation for the decrease
      in dopamine at the conditioned stimulus seen in overtrained animals, for the
      differences between trace and delay conditioning, and for transient bursts of
      dopamine seen at movement initiation. Because each microAgent also includes its
      own exponential discounting factor, the overall agent shows hyperbolic
      discounting, consistent with behavioral experiments.

PMID- 19841750
TI  - Three-dimensional structure of N-terminal domain of DnaB helicase and helicase
      primase interactions in Helicobacter pylori.
AB  - Replication initiation is a crucial step in genome duplication and homohexameric
      DnaB helicase plays a central role in the replication initiation process by
      unwinding the duplex DNA and interacting with several other proteins during the
      process of replication. N-terminal domain of DnaB is critical for helicase
      activity and for DnaG primase interactions. We present here the crystal structure
      of the N-terminal domain (NTD) of H. pylori DnaB (HpDnaB) helicase at 2.2 A
      resolution and compare the structural differences among helicases and correlate
      with the functional differences. The structural details of NTD suggest that the
      linker region between NTD and C-terminal helicase domain plays a vital role in
      accurate assembly of NTD dimers. The sequence analysis of the linker regions from
      several helicases reveals that they should form four helix bundles. We also
      report the characterization of H. pylori DnaG primase and study the helicase
      primase interactions, where HpDnaG primase stimulates DNA unwinding activity of
      HpDnaB suggesting presence of helicase-primase cohort at the replication fork.
      The protein-protein interaction study of C-terminal domain of primase and
      different deletion constructs of helicase suggests that linker is essential for
      proper conformation of NTD to interact strongly with HpDnaG. The surface charge
      distribution on the primase binding surface of NTDs of various helicases suggests
      that DnaB-DnaG interaction and stability of the complex is most probably charge
      dependent. Structure of the linker and helicase-primase interactions indicate
      that HpDnaB differs greatly from E.coli DnaB despite both belong to gram negative
      bacteria.

PMID- 19841751
TI  - Treatment strategy according to findings on pressure-flow study for women with
      decreased urinary flow rate.
AB  - PURPOSE: In women who reported a weak urinary stream, the efficacy of treatment
      chosen according to the urodynamic findings on pressure-flow study was
      prospectively evaluated. MATERIALS AND METHODS: Twelve female patients with
      maximum flow rates of 10 mL/sec or lower were analyzed in the present study. At
      baseline, all underwent pressure-flow study to determine the degree of bladder
      outlet obstruction (BOO) and status of detrusor contractility on Schafer's
      diagram. Distigmine bromide, 10 mg/d, was given to the patients with detrusor
      underactivity (DUA) defined as weak/very weak contractility, whereas urethral
      dilatation was performed using a metal sound for those with BOO (linear passive
      urethral resistance relation 2-6). Treatment efficacy was evaluated using the
      International Prostate Symptom Score (IPSS), uroflowmetry, and measurement of
      postvoid residual urine volume. Some patients underwent pressure-flow study after
      treatment. RESULTS: Urethral dilatation was performed for six patients with BOO,
      while distigmine bromide was given to the remaining six showing DUA without BOO.
      IPSS, QOL index, and the urinary flow rate were significantly improved in both
      groups after treatment. All four of the patients with BOO and one of the three
      with DUA but no BOO who underwent pressure-flow study after treatment showed
      decreased degrees of BOO and increased detrusor contractility, respectively.
      CONCLUSIONS: Both BOO and DUA cause a decreased urinary flow rate in women. In
      the short-term, urethral dilatation and distigmine bromide are efficacious for
      female patients with BOO and those with DUA, respectively.

PMID- 19841753
TI  - Actigraphic recording of manic symptoms induced by methylphenidate.
AB  - Objective. Attention-deficit hyperactivity disorder (ADHD) is a developmental
      disorder characterized by a long-standing pattern of impulsive behavior,
      hyperkinesia, and inattention. Psychostimulants, for example, methylphenidate,
      are the treatment of choice for ADHD both in children, adolescents, and adults.
      Method. The effect of methylphenidate on sleep structure is not well known. We
      studied the effect of long-acting methylphenidate on sleep in adult ADHD
      patients, in a naturalistic treatment setting, using actigraphic and
      polysomnographic recordings. Results. One of our patients experienced manic
      episode after starting methylphenidate. A wrist-worn accelerometer recording
      demonstrated a decrease in the duration and quality of sleep. After
      discontinuation of methylphenidate treatment, the patient's symptoms subsided and
      there was no need for hospital admission. Actigraphic recording showed a decrease
      in the amount and quality of the patient's sleep as triggering factor for the
      manic symptoms. Conclusions. Disruptions of the sleep-wake cycle are probably
      important etiologic factors in mood disorders, especially bipolar disorder. The
      changes in length and quality of sleep described in this case report bear close
      resemblance to those of patients with a manic episode, although these symptoms
      were induced by methylphenidate.

PMID- 19841752
TI  - Linking innate and adaptive immunity: human Vgamma9Vdelta2 T cells enhance CD40
      expression and HMGB-1 secretion.
AB  - gammadelta T cells play an important role in regulating the immune response to
      stress stimuli; however, the mean by which these innate lymphocytes fulfill this
      function remains poorly defined. The main subset of human peripheral blood
      gammadelta T cells responds to nonpeptidic antigens, such as
      isopentylpyrophosphate (IPP), a metabolite in the mevalonate pathway for both
      eukaryote and prokaryote cells. IPP-primed gammadelta T cells significantly
      augment the inflammatory response mediated by monocytes and alphabeta T cells to
      TSST-1, the staphylococcal superantigen that is the major causative agent of
      toxic shock syndrome. Here we show that the small pool of activated peripheral
      gammadelta T cells induces an early upregulation of CD40 on monocytes and the
      local release of High Mobility Group Box-1 (HMGB-1), the molecule designated as
      the late mediator of systemic inflammation. This finding provides a new basis for
      how gammadelta T cells may serve as influential modulators of both endogenous and
      exogenous stress stimuli.

PMID- 19841754
TI  - Difficulty in assessing quality of life outcomes in a fluctuating disease: a
      hypothesis based on gastroparesis.
AB  - An underlying assumption of quality of life outcome research is that after some
      intervention a "steady-state" of quality of life is reached which can be
      identified as an endpoint, and, hence, the "outcome." However, in some disease
      processes, no so such steady-state is reached. The hypothesis presented is that a
      disease process with a waxing and waning course will make it difficult to
      determine a quality of life endpoint. After clinical observation, a pilot study
      of patients with either diabetic or idiopathic gastroparesis with gastric
      neurostimulation their records were reviewed to identify the number of clinic
      visits, the number of clinic visits in which the patients were asymptomatic, much
      improved, improved, no change, worse, or much worse. These changes were defined
      as "transitions." A "transition ratio" was calculated by dividing the number of
      transitions by the number of clinic visits. Preliminary results showed that of 32
      patients, the median number of clinic encounters was 8 (1-35), and the median
      number of transitions 4 (0-22). The average transition ration was 0.56 +/- 0.31.
      In the case of gastroparesis, over half of all clinical encounters were
      associated with a transition. The implication of the hypothesis and preliminary
      finding suggests a difficulty to identify when the symptomatic endpoint was
      reached. Other methods to assess the effects of treatment in such a disease
      process are required to fully understand the effects of treatment on quality of
      life.

PMID- 19841755
TI  - Thyroid Lymphoma as a Cause of Dysphagia and Dyspnea in a Patient without
      Palpable Nodules or Goiter.
AB  - Tumors originating in the neck are well-known causes of progressive dysphagia and
      dyspnea (including stridor), and thyroid lymphoma is an uncommon example.
      Physical examination provides an important first step in the evaluation of such
      complaints, as tumors large enough to produce such symptoms are typically
      considered to be palpable, if not able to be seen grossly. In this case
      presentation, the authors describe a nonsubsternal thyroid lymphoma measuring 3 x
      4 cm at its largest diameter, producing dysphagia and leading to respiratory
      emergency, that was entirely nonpalpable to physical exam even after confirmation
      of its presence by computed tomography.

PMID- 19841756
TI  - Discovery of a symptomatic left anomalous coronary artery from the opposite sinus
      and postoperative considerations.
AB  - This is the case of an 18 year old active duty soldier with symptoms of
      exertional chest pressure and syncope who was found to have anomalous origin of
      the left main coronary artery (LMCA) from the right coronary cusp (RCC) traveling
      partially between the great vessels before taking a septal approach between the
      left ventricular outflow tract (LVOT) and the right ventricular outflow tract
      (RVOT). Anomalous origin of coronary arteries is a rare condition that carries an
      increased risk of angina, myocardial ischemia, and sudden cardiac death (SCD).
      Surgical treatment of such anomalies with both high and lower risk features can
      be challenging, and traditional benefit from surgical correction may not be
      achieved due to complex anatomy. As evident by our patient, this rare condition
      even though benign from sudden death standpoint could be debilitating despite
      best efforts and available resources.

PMID- 19841757
TI  - Acute abdomen: a rare presentation of lung cancer metastasis.
AB  - Surgical emergencies caused by bowel metastases from carcinoma of the lung are
      very rare. We describe two cases of symptomatic gastrointestinal metastatic small
      cell carcinoma: the first one concerns a 69-year-old man with an acute abdomen
      and the second is a 72-year-old man complaining of a gastric ulcer symptoms. We
      also discuss the current management and the prognosis of these patients.

PMID- 19841758
TI  - Is trendy dental medicine really what we want?

PMID- 19841759
TI  - Effect of different cavity disinfectants on shear bond strength of composite
      resin to dentin.
AB  - PURPOSE: The aim of this study was to evaluate the effect of different cavity
      disinfectants on dentin bond strengths of composite resin applied with two
      different adhesive systems. MATERIALS AND METHODS: One hundred mandibular third
      molars were sectioned parallel to the occlusal surface to expose midcoronal
      dentin. The dentin surfaces were polished with waterproof-polishing papers. The
      specimens were randomly divided into 5 groups of 20 each. In group 1, the
      specimens were not treated with any cavity disinfectants and served as control.
      From groups 2 to 5, dentin surfaces were treated with the following cavity
      disinfectants, respectively; 2% chlorhexidine solution, 2.5% NaOCl, 1%
      chlorhexidine gel, 3% H2O2. The specimens were then randomly divided into 2
      subgroups including ten teeth each to evaluate the effect of different bonding
      systems. Dentin bonding systems were applied to the dentin surfaces and the
      composite buildups were created. After the specimens were stored in an incubator
      for 24 h, the shear bond strength was measured at a crosshead speed of 1 mm/min.
      The bond strength data were analyzed with one way analysis of variance and Tukey
      HSD tests. RESULTS: There was no significant difference between chlorhexidine gel
      and control groups regardless of the type of the bonding agent (p > 0.05). On the
      other hand, pretreatment with NaOCl, H2O2 or chlorhexidine solutions had a
      negative effect on the shear bond strength of self-etching bonding systems.
      CONCLUSION: The findings of this study suggest that when NaOCl, H2O2 or
      chlorhexidine solution are used as a cavity disinfectant, an etch-and-rinse
      bonding system should be preferred.

PMID- 19841760
TI  - Influence of bonded enamel margins on dentin bonding stability of one-step self
      etching adhesives.
AB  - PURPOSE: To evaluate the dentin bonding durability of two one-step self-etching
      adhesive systems with and without the presence of surrounding enamel. MATERIALS
      AND METHODS: Tri-S Bond (Kuraray) and G-Bond (GC), commercially available
      adhesive systems, were used in this study. The occlusal enamel was removed in
      order to form a flat, midcoronal dentin surface. The adhesives were applied to
      both the dentin and the surrounding enamel surfaces according to the
      manufacturers' instructions. Resin composite crowns (Clearfil AP-X, Kuraray) were
      incrementally built up with each layer being photocured for 40 s. Half the bonded
      teeth were sectioned perpendicular to the adhesive interface into 0.7-mm-thick
      slabs, and then trimmed to an hourglass shape with a 1 mm2 cross-sectional area
      for microtensile bond strength testing, followed by storage in water for 6 months
      (direct water exposure group, DE). The other half were left untrimmed and stored
      in water for 6 months (indirect water exposure group, IE). As control groups,
      additional bonded teeth were prepared for water storage for 24 h. After the
      designated periods of water storage, the specimens were subjected to bond
      strength testing at a crosshead speed of 1.0 mm/min. The microTBS data were
      statistically analyzed using three-way ANOVA and post-hoc tests (t-test and
      Tukey's HSD comparison tests) (alpha = 0.05). RESULTS: Indirect water exposure of
      the resin/dentin interface did not affect the microTBS of either adhesive after 6
      months water storage (p < 0.05). However, direct exposure to water significantly
      reduced the microTBS of both adhesives to dentin (p < 0.05). In addition, there
      were no significant differences in muTBS between the two adhesive systems for
      each experimental storage condition (p > 0.05). CONCLUSION: The durability of
      resin-dentin bonds was found to be dependent on the method in which the bonded
      specimens were aged in water. Significantly lower bond strengths were observed
      for specimens that were sectioned into an hourglass shape before aging compared
      to those that were sectioned after water storage.

PMID- 19841761
TI  - Effect of X-ray radiation dose on the bond strength of different adhesive systems
      to dentin.
AB  - PURPOSE: To investigate the influence of different x-ray radiation doses on the
      bond strength of adhesive restorations to dentin using different bonding
      strategies. MATERIALS AND METHODS: Flat dentin surfaces on human molars were
      obtained and cylinder-shaped specimens for the microshear bond test were built up
      with a composite (Z250, 3M ESPE), using three adhesive systems: a two-step etch
      and-rinse (Single Bond 2--SB2, 3M ESPE), a two-step self-etching (Clearfil SE
      Bond--CSE, Kuraray), or a single-step self-etching (Adper Prompt--ADP, 3M ESPE).
      The specimens were assigned to 4 groups (n = 10), according to the x-ray dose: 0
      (control), 5, 35, or 70 Gy. Radiation was directed to the surface of the resin
      cylinders. Microshear testing was conducted after 24 h, and the failure modes
      classified under magnification (200X). Data were submitted to two-way ANOVA and
      Holm-Sidak's test (p < or = 0.05). A nonlinear regression analysis was carried
      out with bond strength as dependent variable. RESULTS: Bond strength results were
      dose and material dependent. SB2: control > 5 = 35 > 70; CSE: control = 5 > 35 =
      70; ADP: control = 5 = 35 = 70. Generally, SB2 > CSE > ADP. The nonlinear
      regression plots showed that in general, an increase in radiation dose may
      predict a decrease in bond strength (R2 > or = 0.905). Failure modes were
      dependent on the bonding system, generally with no significant influence of
      radiation. CONCLUSION: X-ray radiation might present a dose-dependent detrimental
      effect on the bond strength of resin composite restorations to dentin.

PMID- 19841762
TI  - Effect of Er:YAG laser on dentin bonding durability under simulated pulpal
      pressure.
AB  - PURPOSE: To evaluate the effects of Er:YAG laser ablation on the microtensile
      bond strength and the nanoleakage of Er:YAG-lased dentin bonded to a self-etching
      adhesive system with and without pulpal pressure. MATERIALS AND METHODS: Twenty
      flat dentin surfaces were obtained from extracted molars. Ten specimens were
      irradiated by Er:YAG laser, other specimens (control group) were ground using
      #600 SiC paper. Direct communication to the pulp chamber was created by cutting
      at a level approximately 1 mm below the cementoenamel junction and parallel to
      the occlusal surface. The experimental groups were exposed to a simulated pulpal
      pressure of 15 cm H2O. Each specimen was restored using an adhesive and a
      photocured composite. The specimens were then sectioned vertically to obtain
      dentin/adhesive slabs. Ninety-six slabs were prepared for microtensile bond
      testing. Sixty-four slabs were immersed in ammoniacal silver nitrate tracer
      solution for 18 h, then rinsed thoroughly, and immersed in photodeveloping
      solution for 6 h prior to their examination by FE-SEM. RESULTS: The method of
      dentin preparation and the pulpal pressure storage condition significantly
      affected the microTBS, while the storage duration did not (p < 0.05). The
      nanoleakage patterns observed in the dentin/bond interface differed depending on
      whether the dentin was conventionally prepared or ablated by Er:YAG laser.
      CONCLUSION: Er:YAG laser ablation to dentin adversely affected the microTBS and
      the sealing ability of SE Bond bonded to dentin under simulated pulpal condition.

PMID- 19841763
TI  - Effect of high frequency ultrasonic agitation on the bond strength of self
      etching adhesives.
AB  - PURPOSE: To investigate the effect of high frequency ultrasonic agitation on the
      microtensile bond strengths of different self-etching adhesives. MATERIALS AND
      METHODS: Thirty-six human molars were wet ground occlusally until dentin was
      exposed. The one-step self-etching adhesives Clearfil S3 Bond, G-Bond, and
      Futurabond NR were tested in this study. In the control groups, bonding
      procedures were performed according to the manufacturers' instructions. In the
      experimental groups, bonding materials were applied with a 1 MHz therapeutic
      ultrasonic device on the dentin surfaces. The composite crown was built up
      incrementally to a height of 5 mm. Each tooth was serially sectioned into
      rectangular beams, and the specimens were subjected to microtensile testing.
      Failure modes were observed under a stereomicroscope and classified. Randomly
      selected specimens from each group were observed with SEM. RESULTS: Two-factor
      ANOVA indicated that both the adhesive system and the ultrasonic agitation effect
      influenced bond strength (p < 0.05). The bond strength of G-Bond adhesive to
      dentin was higher after ultrasonic agitation (p < 0.05), whereas ultrasonic
      agitation of Futurabond and S3 Bond did not affect bond strength values (p >
      0.05). Failure after the test was commonly due to adhesive failure in the dentin.
      CONCLUSION: High-frequency ultrasonic agitation of self-etching adhesives during
      their application may enhance their bonding performance.

PMID- 19841764
TI  - Bond strength of composite core build-up materials to fiber-reinforced posts: a
      microtensile comparison between conventional and wet-ethanol bonding systems.
AB  - PURPOSE: To evaluate the interfacial microtensile bond strength between a fiber
      reinforced post (Rely X Post) and a core material (Multicore Flow) after placing
      different bonding agents. MATERIALS AND METHODS: After post surface treatment, 50
      posts were divided into 5 groups. Group 1: Adper Prompt-L-Pop; group 2:
      SingleBond2; group 3: ScotchBond Multipurpose Plus; group 4: experimental bonding
      system (wet ethanol bonding technique); group 5: control group. After core
      reconstruction, the samples were tested with the microtensile test. Fracture type
      examination and SEM observation followed. Data were statistically analyzed with
      Kruskall-Wallis non-parametric ANOVA. RESULTS: Microtensile testing revealed
      significant differences (p < 0.001). There were no differences between groups 1
      to 4, but there was a statistically significant difference between groups 1 to 4
      and the control. Fracture type observations revealed more adhesive failures than
      cohesive or mixed ones. CONCLUSION: The experimental bonding technique did not
      improve bond strength compared to the different adhesive systems tested. However,
      placing a bonding agent between the post and the core seems to significantly
      increase microtensile bond strength.

PMID- 19841765
TI  - Adhesive properties of bonded orthodontic retainers to enamel: stainless steel
      wire vs fiber-reinforced composites.
AB  - PURPOSE: The objectives of this study were to compare the bond strength of a
      stainless steel orthodontic wire vs various fiber-reinforced composites (FRC)
      used as orthodontic retainers on enamel, analyze the failure types after
      debonding, and investigate the influence of different application procedures of
      stainless steel wires on bond strength. MATERIALS AND METHODS: Caries-free,
      intact human mandibular incisors (N = 80, n = 10 per group) were selected and
      randomly distributed into 8 groups. After etching with 37% H3PO4 for 30 s,
      rinsing and drying, bonding agent (Stick Resin) was applied and light
      polymerized. Then one of the following FRC materials was applied on the flowable
      composite (Stick Flow) using standard molds: group 1: Angelus Fibrex Ribbon;
      group 2: DentaPreg Splint; group 3: ever-Stick Ortho; group 4: Ribbond. In group
      5, Quad Cat Wire was applied in the same manner as in FRC groups. In group 6,
      after applying bonding agent (Stick Resin), Quad Cat Wire was placed directly on
      the tooth surface and covered with Stick Flow composite. In group 7, after
      bonding agent (Heliobond) was applied, Quad Cat Wire was placed directly on the
      tooth surface and covered with Tetric Flow composite. In group 8, after applying
      bonding agent (Heliobond) and polymerization, Tetric Flow composite was applied,
      not polymerized, and Quad Cat Wire was placed and covered with Tetric Flow again.
      Specimens were thermocycled for 6000 cycles between 5 degrees C and 55 degrees C
      and loaded in a universal testing machine under shear stress (crosshead speed: 1
      mm/min) until debonding occurred. The failure sites were examined under an
      optical light microscope. Data were analyzed using one-way ANOVA and the Tukey
      Kramer adjustment test (alpha = 0.05). RESULTS: Significant differences were
      found between the groups (p = 0.0011) (ANOVA). Bond strength results did not
      significantly differ either between the FRC groups (groups 1 to 4) (6.1 +/- 2.5
      to 8.4 +/- 3.7 MPa) (p > 0.05) or the wire groups (groups 5 to 8) (10.6 +/- 3.8
      to 14 +/- 6.7 MPa) (p > 0.05). Failure types varied within the FRC groups, but
      mainly composite was found left adhered on the enamel surface at varying degrees.
      In the stainless steel wire groups, when the retainer was applied onto the
      bonding agent and then covered with flowable resin, partially attached composite
      on the enamel was often found after debonding. When the wires were embedded in
      the flowable composite, the Heliobond group (group 8) showed more adhesive
      failures between the enamel and the composite compared to group 5, where the
      bonding agent was Stick Resin. CONCLUSION: Regardless of their application mode,
      stainless steel orthodontic bonded retainers delivered higher bond strengths than
      those of fiber retainers. The differences were statistically significant compared
      to those of Angelus Fibrex Ribbon and DentaPreg Splint.

PMID- 19841766
TI  - Fracture strength of indirect resin composite laminates to teeth with existing
      restorations: an evaluation of conditioning protocols.
AB  - PURPOSE: This study evaluated the fracture strength and failure types of indirect
      resin-based composite laminates bonded to teeth with aged Class III composite
      restorations that were conditioned according to various protocols. MATERIALS AND
      METHODS: Maxillary central incisors (N = 60) with window-type preparations
      received laminates made of a highly-filled resin composite material (Estenia) (10
      per group).On the mesial and distal side, Class III cavities (3 x 3 mm) were
      prepared using ultrasonic burs and filled with resin composite (Quadrant Anterior
      Shine). The unrestored teeth served as a control group (group 6). All restored
      teeth (n=50) were thermocycled (5 degrees C to 55 degrees C, 6000X) and subjected
      to one of the conditioning protocols: (1) air-particle abrasion with alumina
      particles coated with silica (30-microm SiO2, CoJet)+silanization, (2) air
      particle abrasion with alumina particles (50 microm, Al2O3)+silanization, (3)
      9.5% hydrofluoric acid (HF) for 90 s (Ultradent)+silanization and (4) protocol of
      Clearfil Repair Kit, (5) adhesive resin (Quadrant Unibond Sealer). A three-step
      bonding procedure and dual-polymerizing resin cement (Panavia F 2.0) were
      employed. The inner surfaces of the laminates were conditioned (CoJet-Sand, 30
      mum SiO2) and silanized (ESPE-Sil). All specimens were stored in water at 37
      degrees C for one month prior to the fracture test. RESULTS: A significant
      difference was observed in fracture strength values between the groups (ANOVA, p
      = 0.0261). The only significant difference was between group 2 (299 +/- 103 N)
      and group 3 (471 +/- 126 N) (p = 0.0239) (Tukey's test, alpha = 0.05). The
      majority of failures were type C (35/60) (chipping of the laminate with enamel
      exposure), followed by type B (21/60) (cohesive failure within the composite
      laminate). CONCLUSION: The fracture strengths of the laminates tested did not
      show significant differences, whether they were bonded to existing, aged Class
      III composite restorations or to intact teeth. The failure types, however, varied
      between the groups. The lowest strengths were obtained from the air-particle
      abraded (50 microm, Al2O3) and silanized group.

PMID- 19841767
TI  - Four-year evaluation of a resin composite including nanofillers in posterior
      cavities.
AB  - PURPOSE: The aim of this prospective study was to evaluate the clinical
      performance of the restorative material Ceram.X in combination with an
      experimental one-bottle etch-and-rinse adhesive (K-0127). MATERIALS AND METHODS:
      A single operator placed two Class I or II restorations in molars of 43 patients.
      One molar was restored with Ceram.X/K-0127 (Dentsply DeTrey), the other one with
      Tetric Ceram/Syntac Classic (Ivoclar Vivadent). At baseline, after one, two, and
      four years the restorations were evaluated by a second dentist using modified
      Ryge's criteria. After four years, 27 patients were examined. RESULTS: In one
      patient, both restorations (Class II) had to be removed for root canal treatment
      due to pulpitis. Another Class II Ceram.X restoration (3.8%; 4.3% [1 of 23] of
      Class II restorations) showed score C with regard to wear/anatomical form. Thus,
      the cumulative failure rate was 7.4% in the Ceram.X group (8.3% of Class II
      restorations [2 of 24]) and 3.7% in the Tetric Ceram group (4.2% of Class II
      restorations [1 of 24]). Furthermore, three restorations (11.5%) in each group
      showed score B for anatomical form and marginal integrity. Slight marginal
      discoloration (score B) was found at five Ceram.X restorations (19.2%) and four
      Tetric Ceram restorations (15.4%). Two restorations (7.7%) in each group showed
      slight changes in color stability (score B). No sensitivity, recurrent caries, or
      changes in surface texture were recorded after four years. No statistically
      significant differences were found between the two restorative materials (p >
      0.05). CONCLUSION: After four years of clinical service, 92.6% of Ceram.X/K-0127
      and 96.3% of Tetric Ceram/Syntac Classic restorations performed clinically well.

PMID- 19841768
TI  - The effect of various preparation designs on the survival of porcelain laminate
      veneers.
AB  - PURPOSE: The aim of this clinical study was to observe the service duration of
      porcelain laminate veneers (PLVs) and to estimate the influence of the
      categorical covariates such as location, tooth vitality, preparation depth,
      incisal, gingival and proximal finishing lines, and peripheral tissue type on the
      survival rates of event-free and overall service duration. MATERIALS AND METHODS:
      A total of forty patients (26 women, 14 men; age range: 16 to 50) who had
      received 200 PLVs were evaluated in this study. Median follow-up time was 67.25
      weeks with a range of 12 to 72 weeks. Fifteen of the restored teeth were
      nonvital, while the remaining 185 were vital. Categorical covariates related to
      the restoration design (localization, vitality, preparation depth, incisal,
      proximal, and gingival finishings, and surrounding tissue type) were recorded in
      order to estimate their influence on the survival rates. Survival rates of the
      event-free and overall service duration were calculated with the Kaplan-Meier
      analysis and Mantel log rank test. RESULTS: Twelve failures were observed. The
      most frequent failure type (11 units) was debonding of the restoration from the
      abutment tooth. Nine of them were rebonded and the remaining 2 were remade with a
      different preparation design. The last failure was observed as a coronal fracture
      at the cervical level. The overall survival rates were 99.5%, 99%, 97.5%, 94.9%,
      94.4% and 93.8% at weeks 8, 9, 11, 15, 16, and 34, respectively, with a mean
      estimate of 68.45 weeks. CONCLUSION: PLVs exhibited good clinical results with
      their conservative specifications and high survival rates. The preparation and
      design specifications affect the service duration of PLVs.

PMID- 19841773
TI  - Squaraine dyes in molecular recognition and self-assembly.
AB  - Squaraine dye molecules and their derivatives are gaining significant interest in
      the field of supramolecular chemistry, both in host-guest recognition and self
      assembly. The unique structure and properties of squaraine molecules has led to
      extensive research into their use as sensors. This feature article covers the
      most recent studies (2004-2009) in the development, characterization, and
      application of squaraine dye-based molecular sensors, self-assembly, and their
      use in polymeric materials and biological applications.

PMID- 19841774
TI  - A supramolecular Cu(II) metallocyclophane probe for guanosine 5'-monophosphate.
AB  - We demonstrate Cu(2+) ion induced formation of a novel water soluble
      metallocyclophane [.CuCl(2)](2), which uniquely recognizes guanosine 5'
      monophosphate through changes in emission intensity utilizing synergistic effects
      of electrostatic, coordinative and pi-stacking interactions inside the cavity.

PMID- 19841772
TI  - Discovery and early development of squaraine rotaxanes.
AB  - The chemical and photophysical properties of a fluorescent squaraine dye are
      greatly enhanced when it is mechanically encapsulated inside a tetralactam
      macrocycle. This feature article describes the synthesis, structure, and
      photophysical performance of first-generation squaraine rotaxanes, and shows how
      they can be used as fluorescent imaging probes and chemosensors.

PMID- 19841775
TI  - The unusual self-organising behaviour of a glycosteroidal bolaphile.
AB  - In this communication we report on the self-organising properties of a novel
      asymmetric bolaphile composed of sugar and steroidal units. The material was
      found to exhibit unusual phase changes in that it formed a cubic phase upon
      heating, whereas upon cooling it formed a lamellar phase. This change in property
      was ascribed to kinetic versus thermodynamic behaviour at the phase transition to
      the liquid.

PMID- 19841776
TI  - Layer-by-layer assembly of ruthenium(II) complex anion/layered double hydroxide
      ordered ultrathin films with polarized luminescence.
AB  - Ordered ultrathin films of tris(1,10-phenanthroline-4,7
      diphenylsulfonate)ruthenium(ii) anions and cationic layered double hydroxide
      monolayers have been fabricated by the layer-by-layer assembly technique and show
      well-defined polarized red luminescence.

PMID- 19841777
TI  - Gamma-agostic interactions stabilize the propagating species in the vinyl
      addition polymerization of norbornene.
AB  - Cationic [(tmeda)Pd(OEt(2))(Me)][B(Ar(F))(4)] was synthesized by protonation of
      (tmeda)PdMe(2) and allowed for the first time the nature of the propagating
      species in the vinyl addition polymerization of norbornene to be discerned. In
      this system gamma-agostic interactions stabilize the propagating species and
      permit stepwise monomer insertions to be observed by (1)H NMR spectroscopy. This
      and earlier studies provide a new proposal for the propagating species in ligand
      less late transition metal-catalyzed norbornene polymerizations.

PMID- 19841778
TI  - Metal specificities of Arabidopsis zinc and copper transport proteins match the
      relative, but not the absolute, affinities of their N-terminal domains.
AB  - Metal specificities of zinc and copper transport proteins HMA4 and HMA7 from the
      simple plant Arabidopsis thaliana match the relative, but not the absolute,
      affinities of their amino-terminal domains.

PMID- 19841779
TI  - Direct chemoselective synthesis of glyconanoparticles from unprotected reducing
      glycans and glycopeptide aldehydes.
AB  - Chemoselective oxime coupling was used for facile conjugation of unprotected,
      reducing glycans and glycopeptide aldehydes with core?shell gold nanoparticles
      carrying reactive aminooxy groups on the organic shell.

PMID- 19841780
TI  - Superparamagnetic submicro-megranates: Fe(3)O(4) nanoparticles coated with highly
      cross-linked organic/inorganic hybrids.
AB  - A superparamagnetic pomegranate-like core@shell structure with Fe(3)O(4)@SiO(2)
      nanoparticles as cores and cross-linked PZS as shells was fabricated. The
      Fe(3)O(4)@SiO(2)@PZS hybrid composite shows exellent solvent resistance and water
      dispersion, allowing potentially great biocompatibility and possible tailored
      surface chemistry for applications in biotechnology.

PMID- 19841781
TI  - Organometallic wheels based on coinage metal ions and norbornene: syntheses and
      structural characterization of [M(norbornene)(3)][SbF(6)] (M = Au, Ag, Cu).
AB  - Three closely related organometallic "spoke-wheel" complexes featuring coinage
      metal ions, Au(I), Ag(I), and Cu(I), bonded to three norbornene molecules in
      trigonal planar fashion have been isolated and completely characterized using
      several methods including X-ray crystallography.

PMID- 19841782
TI  - Inhibition of the histone lysine demethylase JMJD2A by ejection of structural
      Zn(II).
AB  - JMJD2A, a 2-oxoglutarate dependent N(epsilon)-methyl lysine histone demethylase,
      is inhibited by disruption of its Zn-binding site by Zn-ejecting compounds
      including disulfiram and ebselen; this observation may enable the development of
      inhibitors selective for this subfamily of 2OG dependent oxygenases that do not
      rely on binding to the highly-conserved Fe(ii)-containing active site.

PMID- 19841783
TI  - Coordination chemistry approach to the long-standing challenge of
      stereocontrolled chemical glycosylation.
AB  - This study clearly demonstrates that a multi-dentate metal coordination to the
      leaving group, along with O-5 and/or a protecting group at O-6, has a strong
      effect on the stereoselectivity of chemical glycosylation.

PMID- 19841784
TI  - A facile iodide-controlled fluorescent switch based on the interconversion
      between two- and three-coordinate copper(I) complexes.
AB  - The first paradigm of halide-controlled interconversion between two- and three
      coordinate copper(i) complexes, [Cu(L(Ph))](ClO(4)) (1?ClO(4)) and [Cu(L(Ph))I]
      (2), where L(Ph) = 1,3-bis-(3,5-dimethyl-pyrazol-1-ylmethyl)-2-phenyl-2,3-dihydro
      1H-perimidine, was presented, which can result in reversible fluorescence
      changes.

PMID- 19841785
TI  - Hydrolysis of phosphohistidine in water and in prostatic acid phosphatase.
AB  - Calculation of the free energy profile for hydrolysis of phosphohistidine using
      ONIOM methodology indicates a much tighter transition state in the enzyme active
      site compared to that in explicit water and elucidates the role of active site
      residues in catalysis.

PMID- 19841786
TI  - Tracking the transition behavior and dynamics of ionic transport in crystalline
      ionic gel electrolytes.
AB  - The transition behavior and dynamics of ionic transport were strongly influenced
      by changes in the crystal structure and interaction field of the crystalline
      ionic gel electrolytes with respect to chemical compositions, as proven by
      impedance, (7)Li NMR, PCA and 2D IR COS.

PMID- 19841787
TI  - An endohedral titanium(III) in a clusterfullerene: putting a non-group-III metal
      nitride into the C(80)-I(h) fullerene cage.
AB  - With the successful isolation of TiSc(2)N@C(80), the first Ti-containing nitride
      clusterfullerene (NCF), a non-group-III metal is stabilized in a NCF for the
      first time.

PMID- 19841788
TI  - Fast catalytic and electrocatalytic oxidation of sodium borohydride on palladium
      nanoparticles and its application to ultrasensitive DNA detection.
AB  - We report an ultrasensitive DNA sensor using the rapid enhancement of
      electrocatalytic activity of DNA-conjugated Pd nanoparticles (NPs); the rapid
      enhancement results from the fast catalytic hydrolysis of NaBH(4) on Pd NPs and
      subsequent fast hydrogen sorption into Pd NPs.

PMID- 19841789
TI  - Temperature control of photoreaction for hydrogen generating gel systems.
AB  - By using a thermo-sensitive polymer network in which the sensitizer and the
      catalyst are immobilized, novel hydrogen generating gel systems capable of
      temperature control of photoreaction have been realized.

PMID- 19841790
TI  - Aromatic ionomers with superacid groups.
AB  - Aromatic polymers containing perfluorosulfonic acid groups show well-developed
      and interconnected ionic clusters, and thus high proton conductivity at wide
      humidity range.

PMID- 19841791
TI  - Utilising (14)C-radiolabelled atom transfer radical polymerisation initiators.
AB  - (14)C-radio-initiated atom transfer radical polymerisations allow direct
      monitoring of the fate of initiating species.

PMID- 19841792
TI  - Encapsulated chloride coordinating with two in-in protons of bridgehead amines in
      an octaprotonated azacryptand.
AB  - An encapsulated chloride in a thiophene-based cryptand is bridged by two in-in
      protons of tertiary amines with an N...Cl(-) distance of 3.048(3) A, similar to
      that observed in Park and Simmons' katapinand chloride complex.

PMID- 19841793
TI  - [(silox)(3)M](2)(mu:eta(1),eta(1)-P(2)) (M = Nb, Ta) and
      [(silox)(3)Nb](2){mu:eta(2),eta(2)-((c)P(3)-(c)P(3))} from (silox)(3)M (M =
      NbPMe(3), Ta) and P(4) (silox = (t)Bu(3)SiO).
AB  - Complexes containing the mu:eta(1),eta(1)-P(2) binding mode of diphosphorus have
      been prepared, along with a P(6)-containing byproduct.

PMID- 19841794
TI  - Elastomeric and degradable polyanhydride network polymers by step-growth thiol
      ene photopolymerization.
AB  - Linear and crosslinked polyanhydrides can be made using photoinitiated thiol-ene
      chemistry, a simple and effective method of making crosslinked structures that
      have surface degradation characteristics.

PMID- 19841795
TI  - Superhydrophobic electrospun POSS-PMMA copolymer fibres with highly ordered
      nanofibrillar and surface structures.
AB  - A POSS-PMMA copolymer has been synthesised by conventional free-radical
      polymerisation reaction. Uniform electrospun fibres from this copolymer showed a
      water contact angle as high as 165 degrees with a sliding angle as low as 6
      degrees . For the first time, we found that the electrospun fibres had a bundled
      nanofibril secondary structure with an ordered POSS morphology on the fibre
      surface.

PMID- 19841796
TI  - Centimetre scale assembly of vertically aligned and close packed semiconductor
      nanorods from solution.
AB  - Assembly of CdS nanorods (8 x 100 nm) into vertically aligned arrays over very
      large areas on a substrate either as a monolayer or several multilayers is shown
      by electrophoresis.

PMID- 19841797
TI  - Direct assessment of molecular transport in mordenite: dominance of surface
      resistances.
AB  - For the first time, macroscopic and microscopic diffusion measurements were
      combined for a single system: n-hexane in mordenite. Using tapered element
      oscillating microbalance and IR microimaging results, we unequivocally proved the
      dominant role of surface barriers for molecular transport.

PMID- 19841798
TI  - Green molecular transformation by a B(12)-TiO(2) hybrid catalyst as an
      alternative to tributyltin hydride.
AB  - The B(12)-TiO(2) hybrid catalyst was effectively used for the radical reactions,
      such as 1,2-migrations of phenyl groups and acyl groups under irradiation by UV
      light, and the selectivity of the reaction was controlled by the solvent system.

PMID- 19841799
TI  - Simple mixed Fe-Zn catalysts for the Suzuki couplings of tetraarylborates with
      benzyl halides and 2-halopyridines.
AB  - Employing co-catalytic zinc reagents facilitates the iron-catalysed Suzuki cross
      coupling of tetraarylborates with both benzyl and 2-heteroaryl halides.

PMID- 19841800
TI  - Copper-catalyzed arene C-H bond cross-coupling.
AB  - A highly regioselective, one-pot sequential iodination-copper-catalyzed cross
      coupling of arene C-H bonds has been developed affording an efficient method for
      biaryl synthesis.

PMID- 19841801
TI  - 1,2,3-Triazole-boranes: stable and efficient reagents for ketone and aldehyde
      reductive amination in organic solvents or in water.
AB  - Air, moisture and thermally stable 1,2,3-triazole-borane complexes were developed
      as new practical reagents for ketone/aldehyde amination with high efficiency and
      excellent substrate diversity.

PMID- 19841802
TI  - Oxidation of cyclic acetals by ozone in ionic liquid media.
AB  - The application of ozone-stable pyrrolidinium based ionic liquids as safe
      reaction media resulted in selective hydroxy ester formation upon ozonation of
      cyclic acetals without using low temperatures or acetylating reagents.

PMID- 19841803
TI  - MRI contrast agent delivery using spore capsules: controlled release in blood
      plasma.
AB  - The exine coatings of spores can be used to encapsulate drug molecules. We have
      demonstrated that these microcapsules can be filled with a commercial
      gadolinium(III) MRI contrast agent (in this proof of concept study Gd-DTPA-BMA
      was used) which is slowly released in plasma due to enzymatic digestion of the
      capsule.

PMID- 19841804
TI  - Label-free aptamer-based sensor using abasic site-containing DNA and a nucleobase
      specific fluorescent ligand.
AB  - A label-free adenosine sensor with emissive response is designed based on an AP
      site-containing aptamer/DNA duplex and a small fluorescent molecule 2-amino-5,6,7
      trimethyl-1,8-naphthyridine (ATMND).

PMID- 19841805
TI  - Switching the direction of plasmon-induced photocurrents by cytochrome c at Au
      TiO(2) nanocomposites.
AB  - A simple route for controlling the direction of plasmon-induced photocurrents at
      gold nanoparticles deposited on TiO(2) films is reported for the first time that
      is based on the electronic state of gold nanoparticles conjugated to redox-active
      cytochrome c and plasmon-enhanced electron exchange.

PMID- 19841806
TI  - Syntheses and X-ray crystal structures of cationic, two-coordinate gold(I) pi
      alkene complexes that contain a sterically hindered o-biphenylphosphine ligand.
AB  - A number of cationic gold pi-alkene complexes of the form {[P(t-Bu)(2)o
      biphenyl]Au(pi-alkene)}(+)SbF(6)(-) were isolated and three were analyzed by X
      ray crystallography.

PMID- 19841807
TI  - Separation of enantiomers with magnetic silica nanoparticles modified by a chiral
      selector: enantioselective fishing.
AB  - Magnetic silica nanoparticles modified by a chiral selector were demonstrated to
      be useful in magnetic field induced separation of enantiomers.

PMID- 19841808
TI  - New reactions of 2-methylenetetrahydropyrans. A three component coupling protocol
      for the synthesis of tetrahydropyranyl ketides.
AB  - Three component coupling of a 2-methylenetetrahydropyran, an activated aldehyde
      or ketone and a secondary nucleophile provides an efficient preparation of
      tetrahydropyranyl ketides, a unit common to many complex natural products.

PMID- 19841809
TI  - Regioselective copper-catalyzed chlorination and bromination of arenes with O(2)
      as the oxidant.
AB  - Electron-rich aromatic C-H bonds undergo regioselective chlorination and
      bromination in the presence of CuX(2), LiX (X = Cl, Br) and molecular oxygen.
      Preliminary mechanistic insights suggest that the bromination and chlorination
      reactions proceed by different pathways.

PMID- 19841810
TI  - Formation of highly selective and efficient interstrand cross-linking to thymine
      without photo-irradiation.
AB  - Interstrand cross-linking (ICL) forming oligodeoxynucleotides (ODNs) have been
      expected to ensure the inhibition of gene expression. In this communication, we
      report a highly efficient and selective ICL reaction to thymine using a 4-amino-2
      vinyl-6-oxopyrimidine derivative.

PMID- 19841811
TI  - From NHC-->germylenes to stable NHC-->germanone complexes.
AB  - The unique isolable N-heterocyclic carbene (NHC)-->germanone complexes and were
      synthesised and structurally characterised, starting from the corresponding NHC
      germylene precursors and through straightforward oxygenation with N(2)O.

PMID- 19841812
TI  - One-step preparation of xanthones via Pd-catalyzed annulation of 1,2
      dibromoarenes and salicylaldehydes.
AB  - A one-step preparation of xanthones via Pd-catalyzed annulation of 1,2
      dibromoarenes and salicylaldehydes was developed.

PMID- 19841813
TI  - Aminations of allylic phenyl ethers via micellar catalysis at room temperature in
      water.
AB  - Especially mild, organic solvent-free conditions have been found that allow for
      allylic ethers to undergo Pd-catalyzed aminations.

PMID- 19841814
TI  - Gd(DO3A-N-alpha-aminopropionate): a versatile and easily available synthon with
      optimized water exchange for the synthesis of high relaxivity, targeted MRI
      contrast agents.
AB  - We report the synthesis of a novel, versatile and easily accessible metal
      chelator, DO3A-N-alpha-aminopropionate, and the relaxometric characterization of
      its Gd(3+) complex, revealing great potential for the development of high
      relaxivity targeted contrast agents for magnetic resonance imaging.

PMID- 19841815
TI  - Open-cellular organic semiconductor thin films by vertical co-deposition using
      sub-100 nm nanosphere templates.
AB  - Vertical co-deposition of sub-100 nm polystyrene sphere templates with water
      soluble small molecule or polymeric semiconductors, followed by solvent vapour
      assisted sphere removal, is shown to be an excellent method for generating porous
      large area organic semiconductor thin films with sub-100 nm open-cellular
      networks, with numerous potential applications in areas such as sensing and
      photovoltaics.

PMID- 19841816
TI  - G-quadruplex recognition by macrocyclic hexaoxazole (6OTD) dimer: greater
      selectivity than monomer.
AB  - Macrocyclic hexaoxazole (6OTD) dimers were designed as candidates for potent G
      quadruplex binders and synthesized.

PMID- 19841817
TI  - Synthesis of framework Ti-substituted, 3-D hexagonal, mesoporous Ti-SBA-12 for
      selective catalytic oxidation.
AB  - Framework Ti-substituted, 3-D hexagonal mesoporous, Ti-SBA-12, obtained for the
      first time by direct hydrothermal synthesis, oxidises bulky molecules such as
      cyclohexene and cyclooctene to the epoxides with >96% selectivity at high
      conversion levels (>60%).

PMID- 19841818
TI  - Sp-sp(3) C-C bond formation via Fe(OTf)(3)/TfOH cocatalyzed coupling reaction of
      terminal alkynes with benzylic alcohols.
AB  - An Fe(OTf)(3)/TfOH cocatalyzed sp-sp(3) C-C bond formation through the coupling
      of benzylic alcohols with terminal alkynes in the absence of base has been
      developed. H(2)O is the sole by-product.

PMID- 19841819
TI  - Steam reforming of methane over ordered mesoporous Ni-Mg-Al oxides.
AB  - The excellent roles of mesopores were revealed clearly in preventing Ni metal
      from sintering as well as in preventing inactive coke accumulation under severe
      reaction conditions of methane steam reforming over ordered mesoporous Ni-Mg-Al
      oxide catalysts.

PMID- 19841822
TI  - An estimated 30-60% of adult patients after stroke do not achieve satisfactory
      motor recovery of the upper limb despite intensive rehabilitation.

PMID- 19841823
TI  - Robotics in neuro-rehabilitation.
AB  - OBJECTIVE: The aims of this study were to review robot-assisted motor and
      functional rehabilitation of the upper limb in patients with stroke and to
      outline possible clinical applications of robotics in neuro-rehabilitation.
      METHODS: Available active systems, with actuators driving the paretic arm, were
      sub-classified by scientific rationale and mechatronic structure as exoskeletons
      or operational-type machines (manipulators). Applicative studies were compared
      for indication of efficacy. RESULTS AND CONCLUSION: Clinical and biomechanical
      evidence available to date suggests substantial efficacy of robot--assisted neuro
      rehabilitation in the recovery of the paretic arm after stroke, enabling longer
      dedicated training sessions with no additional work for the therapist. Further
      investigation of large samples of patients is required to define the relationship
      between disability and residual function, to provide shared criteria of
      evaluation of disability/outcome and protocols of rehabilitation, and to identify
      the expected future role and application of robotics in neuro-rehabilitation.

PMID- 19841824
TI  - Bilateral robot therapy based on haptics and reinforcement learning: Feasibility
      study of a new concept for treatment of patients after stroke.
AB  - OBJECTIVE: To carry out a preliminary feasibility study of a new concept of robot
      therapy for severely impaired patients after stroke. DESIGN: A haptic
      manipulandum connected to a bar that can rotate freely while providing a measure
      of the rotation angle. The controller combines a bilateral reaching task with the
      task of balancing the action of the 2 arms. Reinforcement is given to the subject
      in 2 forms: audio-visual and haptic by means of adaptable force fields. PATIENTS:
      Four highly paretic patients with chronic stroke (Fugl-Meyer score less than 15).
      METHODS: The training cycle consisted of 5 sessions over a period of 2 weeks.
      Each session (45 min) was divided in blocks of 10 pairs of forward/backward
      movements. Performance was determined by evaluating the number of successful
      movements per session, the session-by-session decrease in the assistive field,
      the mean reaching time, and the mean stopping field. RESULTS: All subjects could
      understand the task, appreciated it and improved their performance during
      training. The reaching movements became smoother and quicker; balance errors and
      the magnitude of the resisting field were consistently reduced. CONCLUSION:
      Bilateral robot therapy is a promising technique, provided that it self-adapts to
      the patient's performance. Formal clinical trials should address this point.

PMID- 19841825
TI  - Robot-based rehabilitation of the upper limbs in multiple sclerosis: feasibility
      and preliminary results.
AB  - OBJECTIVE: To make a preliminary evaluation of the feasibility of a robot-based
      rehabilitation protocol for the improvement of upper limb motor co-ordination in
      a group of patients with multiple sclerosis. PATIENTS AND METHODS: Seven patients
      with multiple sclerosis underwent a training protocol of 8 sessions. During each
      session patients performed reaching movements toward virtual targets presented on
      a screen, by moving the handle of a robot, which generated resistive and
      disturbing forces. Each subject was evaluated before and after the treatment by
      means of clinical and instrumental tests. RESULTS: After the 8-session treatment,
      all patients significantly improved the velocity, linearity and smoothness of
      their reaching movements. Moreover, this amelioration was also present in other
      kinds of movement, not executed during the sessions. Results on the Nine-Hole Peg
      Test showed a clinically relevant improvement in the treated arm of 4 out of 7
      patients, suggesting also a transfer of the therapy effect to tasks more related
      to activities of daily living. CONCLUSION: The preliminary results of this pilot
      study suggest that robot therapy can be applied to patients with multiple
      sclerosis in a clinical setting and may be beneficial for reduction of the upper
      limb motor co-ordination deficit.

PMID- 19841826
TI  - Robot therapy for functional recovery of the upper limbs: a pilot study on
      patients after stroke.
AB  - OBJECTIVE: To verify the possibility of administering robot-aided therapy for the
      upper limbs in patients after stroke; to evaluate patients' degree of acceptance
      and compliance with the treatment; to establish if the treatment has an effect on
      motor impairment and functional outcome. DESIGN: Quasi-experimental, uncontrolled
      study. SUBJECTS: Fourteen patients with chronic hemiparesis after stroke.
      METHODS: Patients were treated with a robotic system for the upper limbs (ReoGo;
      Motorika Medical Ltd, Israel). Subjects performed the following assessment, at
      the start (T0), at the end of treatment (T1), and at the follow-up performed one
      month after the end of treatment (T2): Fugl-Meyer test (FM) for upper limbs;
      strength evaluation; Ashworth scale; visual analogue scale (VAS) for pain;
      Frenchay Arm test (FAT); Box and Block test (B & B); Functional Independence
      Measure (FIM); ABILHAND Questionnaire; Timed Up and Go test (TUG); Euro-Quality
      of Life questionnaire and; a VAS for treatment satisfaction were administered to
      the subjects. RESULTS: Total scores of FM, B&B, FAT and FIM showed a
      statistically significant improvement from T0 and T1 (FM p < 0.002, B&B p <
      0.012, FAT p < 0.023, FIM p < 0.007) and from T0 and T2 (FM p < 0.003, B&B p <
      0.011, FAT p < 0.024, FIM p < 0.027). No statistically significant differences
      were found between evaluations at T1 and T2 (FM p < 0.595, B&B p < 0.491, FAT p <
      0.317, FIM p < 0.180). CONCLUSION: The sample was capable of completing the
      treatment and demonstrated good participant satisfaction. This pilot study led to
      the finding of a clinical improvement and excellent patient compliance. It can be
      hypothesized that the results are robot-dependent and that they were learned and
      then maintained. However, the study is limited in that a control group was not
      used. As such, it is desirable to continue this study with a control group, as
      well as by designing a prospective longitudinal randomized controlled trial
      study.

PMID- 19841827
TI  - Robot-mediated therapy for paretic upper limb of chronic patients following
      neurological injury.
AB  - OBJECTIVE: To evaluate the effectiveness of robot-mediated therapy targeted at
      the motor recovery of the upper limb in chronic patients following neurological
      injury. DESIGN: Pre-post treatment study. SUBJECTS: Twenty patients were enrolled
      in the study. METHODS: Robot-mediated therapy was provided to chronic hemiparetic
      patients (acute event had occurred at least one year prior to the study), 3 times
      a week, for 6 weeks. The therapy consisted of goal-directed, planar reaching
      tasks that exercised the hemiparetic shoulder and elbow. The items for the
      shoulder and elbow of Motor Status Score, Modified Ashworth Scale and range of
      motion were used as outcome measures. RESULTS: Statistically significant
      improvements before and after treatment were found in each outcome measure. A 3
      month follow-up evaluation indicated that patients maintained the improvements.
      CONCLUSION: The results confirm that robot-mediated therapy, through short-term,
      but intensive, repetitive and goal-directed trials, contributes to a decrease in
      the upper limb's motor disability in people with a chronic neurological injury by
      reducing motor impairment and shoulder pain. The treatment was well accepted and
      tolerated by patients. No adverse events occurred.

PMID- 19841828
TI  - Upper limb rehabilitation robotics after stroke: a perspective from the
      University of Padua, Italy.
AB  - Rehabilitation robotics is an emerging research field that aims to employ leading
      edge robotic technology and virtual reality systems in the rehabilitation
      treatment of neuro-logical patients. In post-stroke patients with upper limb
      impairment, clinical trials have so far shown positive results in terms of motor
      recovery, but poor efficacy in terms of functional outcome. Much work is needed
      to develop a new generation of rehabilitation robots and clinical protocols that
      will be more effective in helping patients to regain their abilities in
      activities of daily living. This paper presents some key issues in the future
      perspective of upper limb robotic rehabilitation after stroke.

PMID- 19841829
TI  - Kinematic and neurophysiological models: future applications in
      neurorehabilitation.
AB  - This paper emphasizes the importance of developing kinematic and
      neurophysiological methods for evaluating motor and functional recovery in the
      field of neurorehabilitation. From a review of the literature, it is concluded
      that optoelectronic motion analysis and neurophysiological techniques, such as
      the study of nociceptive withdrawal reflex, might constitute useful applications
      for future research.

PMID- 19841830
TI  - Robot-mediated and clinical scales evaluation after upper limb botulinum toxin
      type A injection in children with hemiplegia.
AB  - OBJECTIVE: The aim of this pilot study was to examine changes in different
      aspects of impairment, including spasticity in the upper limbs, of hemiplegic
      children following botulinum toxin type A intervention. Progress was assessed
      using standard clinical measurements and a robotic device. DESIGN: Pre-post
      multiple baseline. SUBJECTS: Six children with hemiplegia. METHODS: Botulinium
      toxin type A injections were administered into the affected upper limb muscles.
      Outcomes were evaluated before and one month after the injection. Outcome
      assessments included: Melbourne Scale, Modified Ashworth Scale (MAS) and Passive
      Range of Motion. Furthermore, a robotic device was employed as an evaluation
      tool. RESULTS: Patients treated with botulinum toxin type A had significantly
      greater reduction in spasticity (MAS, p < 0.01), which explains an improvement in
      upper limb function and quality movement measured with the Melbourne Scale (p <
      0.01). These improvements are consistent with robot-based evaluation results that
      showed statistically significant changes (p < 0.01) following botulinum toxin
      type A injections. CONCLUSION: The upper limb performs a wide variety of
      movements. The multi-joint nature of the task during the robot-mediated
      evaluation required active control of joint interaction forces. There was good
      correlation between clinical scales and robotic evaluation. Hence the robot
      mediated assessment may be used as an additional tool to quantify the degree of
      motor improvement after botulinum toxin type A injections.

PMID- 19841831
TI  - Reach-to-grasp interjoint coordination for moving object in children with
      hemiplegia.
AB  - OBJECTIVE: To evaluate interjoint coordination in children with hemiplegia as
      they reach to grasp objects, in both static and dynamic conditions. An ad hoc
      robotic device was used to study the dynamic condition. DESIGN: Observational
      study. PATIENTS: Six children with hemiplegia and 6 young adults. METHODS:
      Kinematics of the trunk and arm were studied using an optoelectronic system. In
      the dynamic condition the target object, a cup, was moved by the robotic device
      along clockwise and counterclockwise circular trajectories. RESULTS: Two main
      strategies were used to study the onset and offset of shoulder and elbow
      movements and their maximum velocities. The hand velocity profile was bell-shaped
      in the static condition and compatible with ramp movements for the more affected
      side in the dynamic condition. The time to object contact was higher for the more
      affected side in the dynamic condition. The temporal coordination index
      illustrated an immature and less flexible behaviour in children's reaching in all
      the examined conditions. CONCLUSION: Study of the hand velocity profiles, the
      time to object contact and the temporal coordination index highlighted, first,
      the dependence of upper limb interjoint coordination on task, context, residual
      resources and individual solution, and secondly, the sensory-motor deficit
      characteristics of the children's more affected side during dynamic reaching,
      raising the prospect of a promising training context in children with hemiplegia.

PMID- 19841832
TI  - Virtual reality and motor rehabilitation of the upper limb after stroke: a
      generation of progress?
AB  - AIM: To review the rationale, criteria of application, potentialities and limits
      of the available procedures for upper limb rehabilitation in virtual reality
      setups. METHODS: Classification of the available virtual reality setups and
      comparison among published studies, with focus on the criteria of motor
      impairment and recovery assessment, rehabilitation procedures, and efficacy.
      RESULTS AND CONCLUSION: The studies completed to date support application of
      virtual reality methods in the treatment of the paretic upper limb after stroke,
      but the superiority of virtual reality methods in comparison with conventional
      procedures currently in use is still unproven. Larger samples, adequate
      controlled study design and follow-up, greater homogeneity in the selection
      criteria and parameters measuring severity of stroke, motor impairment and
      recovery are necessary.

PMID- 19841833
TI  - Robot-assisted rehabilitation of the paretic upper limb: rationale of the ARAMIS
      project.
AB  - Robot ARAMIS (Automatic Recovery Arm Motility Integrated System) is intended to
      provide the therapist with novel and time/cost-efficient approaches to the
      rehabilitation of the paretic upper limb after stroke. The system has been
      designed and implemented based on common experience in rehabilitation and will
      provide a robot-patient interaction compensating for some intrinsic limitations
      of traditional treatments. Rationale, technical characteristics and application
      are described in detail here.

PMID- 19841834
TI  - The ARAMIS project: a concept robot and technical design.
AB  - OBJECTIVE: To describe the ARAMIS (Automatic Recovery Arm Motility Integrated
      System) project, a concept robot applicable in the neuro-rehabilitation of the
      paretic upper limb after stroke. Methods, results and conclusion: The rationale
      and engineering of a state-of-the-art, hardware/software integrated robot system,
      its mechanics, ergonomics, electric/electronics features providing control,
      safety and suitability of use are described. An ARAMIS prototype has been built
      and is now available for clinical tests. It allows the therapist to design neuro
      rehabilitative (synchronous or asynchronous) training protocols in which sample
      exercises are generated by a single exoskeleton (operated by the patient's
      unaffected arm or by the therapist's arm) and mirrored in real-time or offline by
      the exoskeleton supporting the paretic arm.

PMID- 19841835
TI  - Exercises for paretic upper limb after stroke: a combined virtual-reality and
      telemedicine approach.
AB  - OBJECTIVE: Telerehabilitation enables a remotely controlled programme to be used
      to treat motor deficits in post-stroke patients. The effects of this
      telerehabilitation approach were compared with traditional motor rehabilitation
      methods. DESIGN: Randomized single-blind controlled trial. PATIENTS: A total of
      36 patients with mild arm motor impairments due to ischaemic stroke in the region
      of the middle cerebral artery. METHODS: The experimental treatment was a virtual
      reality-based system delivered via the Internet, which provided motor tasks to
      the patients from a remote rehabilitation facility. The control group underwent
      traditional physical therapy for the upper limb. Both treatments were of 4 weeks
      duration. All patients were assessed one month prior to therapy, at the
      commencement and termination of therapies and one month post-therapy, with the
      Fugl-Meyer Upper Extremity, the ABILHAND and the Ashworth scales. RESULTS: Both
      rehabilitative therapies significantly improved all outcome scores after
      treatment, but only the Fugl-Meyer Upper Extremity scale showed differences in
      the comparison between groups. CONCLUSION: Both strategies were effective, but
      the experimental approach induced better outcomes in motor performance. These
      results may favour early discharge from hospital sustained by a
      telerehabilitation programme, with potential beneficial effects on the use of
      available resources.

PMID- 19841836
TI  - Vocational rehabilitation: an educational review.
AB  - The aim of this review is to describe aspects of vocational rehabilitation
      relevant for a physician aiming to become a specialist in physical and
      rehabilitation medicine (PRM). The review discusses the epidemiology of
      incapacity for work, the major patient groups in vocational rehabilitation
      (musculoskeletal and psychiatric diagnoses comprise approximately 50-70% of the
      patients), the influence of different kinds of environmental and individual risk
      factors on work resumption (such as the legal framework, application of the law,
      resources for rehabilitation and its effectiveness, the degree of co-operation
      between vocational rehabilitation agencies, economic factors/labour market
      situation, medical and personal factors). The review describes different models
      of vocational rehabilitation, the effectiveness of various vocational
      rehabilitation programmes on work resumption or sick leave (where strong evidence
      is reported for multi-modal rehabilitation programmes for patients with long
      lasting musculoskeletal pain). Finally, there are sections about the PRM
      physician's history-taking in vocational rehabilitation (using the International
      Classification of Functioning, Disability and Health (ICF)), and report writing
      with a structure where ICF body functions and activity limitations are reported
      separately.

PMID- 19841837
TI  - Effects of physiotherapy in patients with shoulder impingement syndrome: a
      systematic review of the literature.
AB  - OBJECTIVE: To critically summarize the effectiveness of physio-therapy in
      patients presenting clinical signs of shoulder impingement syndrome. DESIGN:
      Systematic review. METHODS: Randomized controlled trials were searched
      electronically and manually from 1966 to December 2007. Study quality was
      independently assessed by 2 reviewers using the Physiotherapy Evidence Database
      (PEDro) scale. If possible, relative risks and weighted mean differences were
      calculated for individual studies, and relative risks or standardized mean
      differences for pooled data, otherwise results were summarized in a best evidence
      synthesis. RESULTS: Sixteen studies were included, with a mean quality score of
      6.8 points out of 10. Many different diagnostic criteria for shoulder impingement
      syndrome were applied. Physio-therapist-led exercises and surgery were equally
      effective treatments for shoulder impingement syndrome in the long term. Also,
      home-based exercises were as effective as combined physiotherapy interventions.
      Adding manual therapy to exercise programmes may have an additional benefit on
      pain at 3 weeks follow-up. Moderate evidence exists that passive treatments are
      not effective and cannot be justified. CONCLUSION: This review shows an equal
      effectiveness of physiotherapist-led exercises compared with surgery in the long
      term and of home-based exercises compared with combined physiotherapy
      interventions in patients with shoulder impingement syndrome in the short and
      long term; passive treatments cannot be recommended for shoulder impingement
      syndrome. However, in general, the samples were small, and different diagnostic
      criteria were applied, which makes a firm conclusion difficult. More high-quality
      trials with longer follow-ups are recommended.

PMID- 19841838
TI  - Perceived barriers to and facilitators of physical activity in young adults with
      childhood-onset physical disabilities.
AB  - OBJECTIVE: To explore the main barriers to and facilitators of physical activity
      in young adults with childhood-onset physical disabilities. DESIGN: Qualitative
      study using focus groups. PARTICIPANTS: Sixteen persons (12 men and 4 women) aged
      22.4 (standard deviation 3.4) years, of whom 50% were wheelchair-dependent,
      participated in the study. Eight were diagnosed with myelomeningocele, 4 with
      cerebral palsy, 2 with acquired brain injury and 2 with rheumatoid arthritis.
      METHODS: Three focus group sessions of 1.5 h were conducted using a semi
      structured question route to assess perceived barriers to and facilitators of
      physical activity. Tape recordings were transcribed verbatim and content
      analysed. According to the Physical Activity for People with a Physical
      Disability model, barriers and facilitators were subdivided into personal factors
      and environmental factors. RESULTS: Participants reported several barriers
      related to attitude and motivation. In addition, lack of energy, existing injury
      or fear of developing injuries or complications, limited physical activity
      facilities, and lack of information and knowledge, appeared to be barriers to
      physical activity. Fun and social contacts were mentioned as facilitators of
      engaging in physical activity, as well as improved health and fitness.
      CONCLUSION: Young adults with childhood-onset physical disabilities perceived
      various personal and environmental factors as barriers to or facilitators of
      physical activity. These should be taken into account when developing
      interventions to promote physical activity in this population.

PMID- 19841839
TI  - Test-retest and alternate forms reliability of the assisting hand assessment.
AB  - OBJECTIVE: The Assisting Hand Assessment (AHA) has earlier demonstrated excellent
      validity and rater reliability. This study aimed to evaluate test-retest
      reliability of the AHA and alternate forms reliability between Small kids vs
      School kids AHA and the 2 board games in School kids AHA. DESIGN: Test-retest and
      alternate forms reliability was evaluated by repeated testing with 2 weeks
      interval. SUBJECTS: Fifty-five children with unilateral cerebral palsy, age range
      2 years and 3 months to 11 years and 2 months. METHODS: Intraclass correlation
      coefficients and smallest detectable difference were calculated. Common item and
      common person linking plots using Rasch analysis and Bland-Altman plots were
      created. RESULTS: Intraclass correlation coefficients for test-retest was 0.99.
      Alternate forms intraclass correlation coefficients were 0.99 between Small kids
      and School kids AHA and 0.98 between board games. Smallest detectable difference
      was 3.89 points (sum scores). Items in common item linking plots and persons in
      common person linking plots were within 95% confidence intervals, indicating
      equivalence across test forms. CONCLUSION: The AHA has excellent test-retest and
      alternate forms reliability. A change of 4 points or more between test occasions
      represents a significant change. Different forms of the AHA give equivalent
      results.

PMID- 19841840
TI  - Frailty and incidence of activities of daily living disability among older
      Mexican Americans.
AB  - OBJECTIVE: To examine the association between frailty status and incidence of
      disability among non-disabled older Mexican Americans. DESIGN: A 10-year
      prospective cohort study. SUBJECTS: A total of 1645 non-institutionalized Mexican
      Americans aged 67 years and older from the Hispanic Established Population for
      the Epidemiological Study of the Elderly (H-EPESE), who reported no limitation in
      activities of daily living at baseline. METHODS: Frailty was defined as meeting 3
      or more of the following components: (i) unintentional weight loss of > 2.26 kg;
      (ii) weakness (lowest 20% in hand grip strength); (iii) self-reported exhaustion;
      (iv) slow walking speed; and (v) low physical activity level. Socio-demographic
      factors, Mini Mental State Examination, medical conditions, body mass index, and
      self-reported activities of daily living were obtained. RESULTS: Of the 1645 non
      disabled subjects at baseline, 820 (50%) were not frail, 749 (45.7%) were pre
      frail, and 71 (4.3%) were frail. The hazard ratio of activities of daily living
      disability at 10-year follow-up for pre-frail subjects was 1.32 (95% confidence
      interval 1.10-1.58) and 2.42 (95% confidence interval 70-3.46) for frail subjects
      compared with not frail subjects. This association remained statistically
      significant after controlling for potential confounding factors at baseline.
      CONCLUSION: Pre-frail and frail status in older Mexican Americans was associated
      with an increased risk of activities of daily living disability over a 10-year
      period among non-disabled subjects.

PMID- 19841841
TI  - Validity of electrical stimulus magnitude matching in chronic pain.
AB  - OBJECTIVE: To examine the validity of the PainMatcher in chronic pain. DESIGN:
      Comparison of parallel pain estimates from visual analogue scales with electrical
      stimulus magnitude matching. PATIENTS: Thirty-one patients with chronic
      musculoskeletal pain. METHODS: Twice a day ongoing pain was rated on a standard
      100-mm visual analogue scale, and thereafter magnitude matching was performed
      using a PainMatcher. The sensory threshold to electrical stimulation was tested
      twice on separate occasions. RESULTS: In 438 observations visual analogue scale
      ranged from 3 to 95 (median 41) mm, and PainMatcher magnitudes from 2.67 to 27.67
      (median 6.67; mean 7.78) steps. There was little correlation between visual
      analogue scale and magnitude data (r = 0.29; p < 0.0001). The mean sensory
      threshold was 3.67 steps, indicating that the PainMatcher, on average, stimulated
      at 2.1 times the perception threshold at matching point. CONCLUSION: Electrical
      magnitude matching of chronic pain intensity elicited limited activation of nerve
      fibres at 2.0-2.2 times sensory threshold, indicating that the induced pain was
      evoked by coarse nociceptive Adelta fibres. While the visual analogue scale
      estimates covered the whole range of the instrument, the PainMatcher readings
      utilized only a small part of the instrument range and, importantly, had little
      or no relation to the visual analogue scale estimates. The validity of the
      PainMatcher procedure is doubtful.

PMID- 19841842
TI  - Factors related to fatigue in women and men with early rheumatoid arthritis: the
      Swedish TIRA study.
AB  - OBJECTIVE: To study whether there are differences between women and men with
      regard to the reported level of fatigue, to explore the strength of the relations
      between fatigue and disease activity, pain, sleep disturbance, mental health, and
      activity limitation in early rheumatoid arthritis, and to explore the consistency
      of such findings. DESIGN: Analyses and comparisons of cross-sectional data.
      SUBJECTS: Two hundred and seventy-six patients, 191 women and 85 men, with early
      rheumatoid arthritis were included. METHODS: Patients were examined with respect
      to 28-joint count disease activity score, and disability variables reflecting
      pain, sleep disturbance, fatigue, mental health, and activity limitation, at
      follow-ups at 1, 2 and 3 years after diagnosis. RESULTS: Women reported somewhat
      more fatigue than men. Fatigue was closely and rather consistently related to
      disease activity, pain and activity limitation, and also to mental health and
      sleep disturbance. CONCLUSION: Although this study does not permit conclusions to
      be drawn about causal directions, statistical relationships may be related to
      clinical conceptions about causation: when disease activity can be significantly
      reduced by pharmacological treatment this may have a positive effect on fatigue.
      Specific treatment with respect to the mentioned disability aspects that are
      related to fatigue is also a clinically reasonable strategy.

PMID- 19841843
TI  - Development and reproducibility of a short questionnaire to measure use and
      usability of custom-made orthopaedic shoes.
AB  - OBJECTIVE: To develop a short and easy to use questionnaire to measure use and
      usability of custom-made orthopaedic shoes, and to investigate its
      reproducibility. DESIGN: Development of the questionnaire (Monitor Orthopaedic
      Shoes) was based on a literature search, expert interviews, 2 expert meetings,
      and exploration and testing of reproducibility. The questionnaire comprises 2
      parts: a pre part, measuring expectations; and a post part, measuring
      experiences. PATIENTS: The pre part of the final version was completed twice by
      37 first-time users before delivery of their orthopaedic shoes. The post part of
      the final version was completed twice by 39 first-time users who had worn their
      orthopaedic shoes for 2-4 months. RESULTS: High reproducibility scores (Cohen's
      kappa > 0.60 or intra class correlation > 0.70) were found in all but one
      question of both parts of the final version of the Monitor Orthopaedic Shoes
      questionnaire. The smallest real difference on a visual analogue scale (100 mm)
      ranged from 21 to 50 mm. It took patients approximately 15 minutes to complete
      one part. CONCLUSION: Monitor Orthopaedic Shoes is a practical and reproducible
      questionnaire that can measure relevant aspects of use and usability of
      orthopaedic shoes from a patient's perspective.

PMID- 19841844
TI  - Three-year cost analysis of function-centred versus pain-centred inpatient
      rehabilitation in patients with chronic non-specific low back pain.
AB  - OBJECTIVE: To compare costs of function- and pain-centred inpatient treatment in
      patients with chronic low back pain over 3 years of follow-up. DESIGN: Cost
      analysis of a randomized controlled trial. PATIENTS: A total of 174 patients with
      chronic low back pain were randomized to function- or pain-centred inpatient
      treatment. METHODS: Data on direct and indirect costs were gathered by
      questionnaires sent to patients, health insurance providers, employers, and the
      Swiss Disability Insurance Company. RESULTS: There was a non-significant
      difference in total medical costs after 3 years' follow-up. Total costs were
      77,305 Euros in the function-centred inpatient treatment group and 83,085 Euros
      in the pain-centred inpatient treatment group. Likewise, indirect costs after 3
      years from lost work days were non-significantly lower in the function-centred in
      patient treatment group (6354 Euros; 95% confidence interval -20,892, 8392) and
      direct medical costs were non-significantly higher in the function-centred
      inpatient treatment group (574 Euros; 95% confidence interval -862, 2011).
      CONCLUSION: The total costs of function-centred and pain-centred inpatient
      treatment were similar over the whole 3-year follow-up.

PMID- 19841845
TI  - Effect of 12-week tai chi chuan exercise on peripheral nerve modulation in
      patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To examine the effect of tai chi chuan exercise on peripheral nerve
      modulation in patients with type 2 diabetes mellitus. DESIGN: Parallel group
      comparative study with a pre- and post- design. SUBJECTS: Twenty-eight
      participants with diabetes mellitus and 32 healthy adult controls from
      communities in Kaohsiung, Taiwan. METHODS: Cheng's tai chi chuan, 3 times a week
      for 12 weeks. Fasting blood glucose levels, insulin resistance index and nerve
      conduction studies were measured. RESULTS: A 12-week tai chi chuan programme
      significantly improved fasting blood glucose (p = 0.035) and increased nerve
      conduction velocities in all nerves tested (p = 0.046, right; p = 0.041, left) in
      diabetic patients. Tai chi chuan exercise did not advance the nerve conduction
      velocities of normal adults; however, it significantly improved the motor nerve
      conduction velocities of bilateral median and tibial nerves, and distal sensory
      latencies of bilateral ulnar nerves in diabetic patients. Tai chi chuan exercise
      had no significant effect on amplitudes of all nerves tested in diabetic
      patients. CONCLUSIONS: Results from this study suggest that fasting blood glucose
      and peripheral nerve conduction velocities in diabetic patients can be improved
      by 12 weeks tai chi chuan exercise. A further larger randomized controlled
      clinical trial with longer follow-up time is needed.

PMID- 19841846
TI  - Prediction of depressive symptoms up to three years post-stroke.
AB  - OBJECTIVE: To describe the long-term course of depressive symptoms up to 3 years
      post-stroke and to develop a prediction model for depressive symptoms 1 and 3
      years post-stroke. DESIGN: Longitudinal follow-up study. PATIENTS: Data were
      analysed for 131 patients with a first-ever supratentorial stroke admitted for
      inpatient rehabilitation in the Netherlands METHODS: The Center for Epidemiologic
      Studies-Depression scale was used to assess post-stroke depressive symptoms at 6
      months, 1 and 3 years post-stroke. RESULTS: Post-stroke depressive symptoms were
      present 6 months, 1 year and 3 years post-stroke in 23.7%, 25.2% and 16.0% of the
      patients, respectively. At all 3 assessments post-stroke depressive symptoms were
      absent in 65.6% of the patients and present in 12.2% of the patients. Of the
      patients with post-stroke depressive symptoms 6 months post-stroke, 41.9% had
      recovered from post-stroke depressive symptoms 3 years post-stroke. The most
      important predictor of post-stroke depressive symptoms 1 and 3 years post-stroke
      was post-stroke depressive symptoms 6 months post-stroke (area under the curve
      0.75 and 0.85). Male gender was an additional predictor for post-stroke
      depressive symptoms 3 years post-stroke. CONCLUSION: Long-term post-stroke
      depressive symptoms are highly predictable at 6 months post-stroke. If a patient
      has not recovered from post-stroke depressive symptoms within the first 6 months
      post-stroke there is a high risk of chronic post-stroke depressive symptoms.

PMID- 19841847
TI  - Participation: a comparative analysis of multiple rehabilitation stakeholders'
      perspectives.
AB  - OBJECTIVE: To examine how participation is conceptualized by different
      rehabilitation stakeholder groups. DESIGN: Qualitative case study design.
      SUBJECTS: A total of 148 participants from different stakeholder groups in 2 US
      states and the District of Columbia. Stakeholders included people with
      disabilities (n = 63), caregivers (n = 28), rehabilitation professionals (n =
      32), funders (n = 10), and policy makers (n = 15). METHODS: Eighteen focus groups
      were conducted to examine what participation means, how it is conceptualized, and
      the barriers to realizing full participation. Focus groups were transcribed
      verbatim; transcripts were analyzed using a constructivist grounded theory
      approach. RESULTS: Stakeholders agreed on 3 primary domains of participation: (i)
      productivity and economic participation; (ii) social participation and
      relationships; and (iii) leisure/recreational participation. Participation within
      each domain was characterized by its diversity, individuality and environmental
      influences. Differences emerged in the emphasis stakeholders placed on the
      relevance of the participation domains in the lives of people with disabilities.
      Stakeholders' emphasis was influenced by their roles within the rehabilitation
      process and created distinct needs for participation outcome measures.
      CONCLUSION: While there was agreement about what constitutes participation,
      stakeholders emphasized different aspects of participation based on their
      positions in the rehabilitation process. Recommendations are offered for
      integrating study findings into the development of new participation measures.

PMID- 19841848
TI  - Search for primitive Methanopyrus based on genetic distance between Val- and Ile
      tRNA synthetases.
AB  - Since evidence indicates that the Last Universal Common Ancestor (LUCA) was
      phylogenetically closest to Methanopyrus kandleri among living organisms with
      elucidated genomes, this study has been directed to a search for the most
      primitive Methanopyrus lineage. For this purpose, the divergence of valyl-tRNA
      synthetase (ValRS) and isoleucyl-tRNA synthetase (IleRS) was employed as a
      measure of primitivity. Comparison of Methanopyrus kandleri and the Methanopyrus
      isolates GC34 and GC37 from the Pacific Ocean and KOL6, TAG1, TAG11, and SNP6
      from the Atlantic Ocean established that the Pacific lineages are more primitive
      than the Atlantic lineages. Both the groups, however, are younger than
      environmental genomes from the Kairei Field of Central Indian Ridge in the Indian
      Ocean. These results showed that different Methanopyrus isolates differ
      significantly with respect to ValRS-IleRS divergence. On this basis, genomes
      giving rise to the ValRS and IleRS gene fragments from the Central Indian Ridge
      represent the most primitive Methanopyrus, phylogenetically the oldest living
      lineage closest to LUCA.

PMID- 19841849
TI  - The evolution of RecD outside of the RecBCD complex.
AB  - The common understanding of the function of RecD, as derived predominantly from
      studies in Escherichia coli, is that RecD is one of three enzymes in the RecBCD
      double-stranded break repair DNA recombination complex. However, comparative
      genomics has revealed that many organisms possess a recD gene even though the
      other members of the complex, recB and recC, are not present. Further,
      bioinformatic analyses have shown that there is substantial sequence
      dissimilarity between recD genes associated with recB and recC (recD1), and those
      that are not associated with recBC (recD2). Deinococcus radiodurans, known for
      its extraordinary DNA repair capability, is one such organism that does not
      possess either recB or recC, and yet does possess a recD gene. The recD of D.
      radiodurans was deleted and this mutant was shown to have a capacity to repair
      double-stranded DNA breaks equivalent to wild-type. The phylogenetic history of
      recD was studied using a dataset of 120 recD genes from 91 fully sequenced
      species. The analysis focused upon the role of gene duplication and functional
      genomic context in the evolution of recD2, which appears to have undergone
      numerous independent events resulting in duplicate recD2 genes. The role of RecD
      as part of the RecBCD complex appears to have a divergence from an earlier
      ancestral RecD function still preserved in many species including D. radiodurans.

PMID- 19841850
TI  - Optimization models and the structure of the genetic code.
AB  - The codon assignment of the quasi-universal genetic code can be assumed to have
      resulted from the evolutionary pressures that prevailed when the code was still
      evolving. Here, we review studies of the structure of the genetic code based on
      optimization models. We also review studies that, from the structure of the code,
      attempt to derive aspects of the primordial circumstances in which the genetic
      code froze. Different rationales are summarized, compared with experimental data,
      discussed in the context of the transition from a RNA world to a DNA-protein
      world, and linked to the emergence of the last universal common ancestor.

PMID- 19841851
TI  - Lamina propria of the human vocal fold: histomorphometric study of collagen
      fibers.
AB  - BACKGROUND: Since the seminal work of M. Hirano, which defined the three-layered
      lamina propria of the human vocal fold, there has been confusion in the labeling
      of each layer. Recent studies described the composition of fibers and
      interstitial molecules within the lamina propria leading to various biomechanical
      properties. However, collagen fibers appear as the most important structure
      component. METHODS: We used an optical analysis and the picrosirius-polarization
      method to describe collagen fibers from six adult and two fetal human larynges
      fixed in formalin and frontally sectioned in the middle part of the vocal fold.
      RESULTS: The deep layer of the lamina propria is the most densely organized band
      of collagen fibers penetrating the superficial muscle bundles of the vocal
      muscle. The mean thickness of this layer is about 36% of the lamina propria and
      shows a network of strongly birefringent fibers (collagen type I and III). The
      superficial layer of the lamina propria is a narrow band of collagen fibers
      immediately below the basement membrane of the epithelium. The mean thickness of
      this layer is about 13% of the lamina propria and shows strong birefringent
      fibers. The intermediate layer is the less densely organized band between the
      deep and superficial layers. The mean thickness of this layer is about 51% of the
      lamina propria and shows clear, green weakly birefringent fibers characterized as
      collagen type III. The fetal lamina propria contains only a monolayer
      distribution of loose collagen fibers between the epithelium and the vocal
      muscle. CONCLUSION: These results help describe the distribution of collagen
      fibers within the lamina propria of the human vocal fold and have implications to
      understand the cover-body theory of voice production both in the adult and
      newborn.

PMID- 19841853
TI  - Effect of beer consumption on levels of complex I and complex IV liver and heart
      mitochondrial enzymes and coenzymes Q9 and Q10 in adriamycin-treated rats.
AB  - BACKGROUND: There is increasing evidence indicating that the dietary intake of
      food with high antioxidant capacity may protect mitochondria from damage and
      exert positive effects on different pathogenic processes. AIM OF THE STUDY: The
      present study was designed to evaluate the possible protective effect of alcohol
      free beer intake on chain components dysfunction of liver and heart mitochondria,
      and to compare with the effect of alcohol beer intake. METHODS: The study was
      carried out in rat heart and liver mitochondria by inducing with Adriamycin the
      dysfunction of the respiratory chain. Heart and liver mitochondria were isolated
      from rats and subjected to oxidative stress with two doses of Adriamycin (5
      mg/Kg) 7 days from the beginning of consumption of both alcohol-free and alcohol
      beer during 31 days. Complexes I and IV and the levels of coenzymes Q(9) and
      Q(10) were evaluated and compared with a control group. RESULTS: Liver and heart
      mitochondria isolated from rats treated with Adryamicin showed a decrease in
      levels of complex I and complex IV enzymatic activity and in levels of coenzymes
      Q(9) and Q(10). Beer intake for itself does not affect any of the studied
      parameters. Therefore, the consumption of both alcohol and alcohol-free beer by
      rats treated with Adriamycin prevents the inhibition of enzymatic activities of
      complexes I and IV and the oxidation of coenzymes Q(9) and Q(10) in rat heart and
      liver mitochondria. CONCLUSIONS: These results indicate that alcohol-free beer
      prevents adriamycin-induced damage to mitochondrial chain components and,
      therefore, helps to prevent mitochondrial dysfunction.

PMID- 19841854
TI  - Intra-operative MRI-assisted spinal localization.
AB  - BACKGROUND: Level localization in the thoracic spine can be problematic. We
      describe a new method that can be used in difficult cases, e.g., ones where
      lesions are mid-thoracic, small, or only visible on MRI. METHODS: Intra
      operatively, a midline incision was made and the thoracic spinous processes were
      exposed. A length of contrast-filled tubing was wound around the processes and
      the incision was temporarily closed and the patient was transferred to the
      radiology department for MRI under general anesthetic. Upon return to theatre,
      the cross sections of contrast-filled tubing and the lesion itself were visible
      on the MRI scan, allowing localization of the level. FINDINGS: This method was
      accurate and minimized the extent of bone removal required for access.
      CONCLUSIONS: This technique, while not appropriate in every case, is repeatable,
      and does not require specialized equipment or training. It is an extremely
      accurate method of localization for difficult cases.

PMID- 19841855
TI  - Early acute hemispheric stroke after carotid endarterectomy. Pathogenesis and
      management.
AB  - PURPOSE: A major stroke after carotid endareterectomy (CEA) is an event that
      should be managed according to a planned strategy. Literature data on this issue
      are not definitive. We reviewed our series in the attempt to define an algorithm
      of treatment if this complication occurs. METHODS: A consecutive series of 413
      CEAs in 390 patients was considered. All operations were performed under general
      anaesthesia and EEG monitoring. An indwelling shunt was inserted only according
      to EEG changes. Direct closure of the arteriotomy was performed in all cases.
      Intraoperative ultrasound was not routinely employed before 2004. Patients who
      suffered from the new onset of an ischaemic hemispheric deficit or the worsening
      of a pre-existing deficit within 72 h after surgery were included in the present
      study. RESULTS: Sixteen patients (3.9%) suffered from perioperative stroke. Seven
      patients presented neurological deficits that rapidly and spontaneously resolved.
      In nine cases (2.2%) a major stroke occurred. Acute occlusion of the internal
      carotid artery (ICA), with or without embolic blocking of the omolateral M1
      segment, occurred in eight cases; in one case a patent ICA was associated with
      the occlusion of two frontal branches of the omolateral middle cerebral artery.
      Seven cases were reoperated on. The ICA was reopened in all these cases except
      one. Among these seven cases, three (42%) had a good outcome. CONCLUSIONS: A
      major stroke after CEA is caused, in most of cases, by the acute ICA occlusion
      with or without intracerebral embolic occlusion. Reopening of the occluded ICA
      gives good results when intracerebral vessels are patent and when the occluded
      ICA is satisfactorily reopened. An algorithm of planned reactions in case of
      perioperative stroke is finally proposed.

PMID- 19841856
TI  - A new approach to the treatment of cerebral vasospasm: the angiographic effects
      of tadalafil on experimental vasospasm.
AB  - BACKGROUND: The pathogenesis of cerebral vasospasm is likely to be
      multifactorial. Strong evidence has indicated that decreasing levels of NO after
      SAH seem to be important. A PDE-V inhibitor, tadalafil, theoretically increases
      NO levels. Our study investigated the vasodilatory efficacy of tadalafil on the
      cerebral arteries with measurement of basilar artery diameters on angiography.
      METHODS: We used 42 male Wistar-Albino rats to test our hypothesis. They were
      assigned randomly into the following seven groups: group 1: control (only
      saline), group 2: SAH only (killed on day 2), group 3: SAH + tadalafil (killed on
      day 2), group 4: SAH only (killed on day 4), group 5: SAH + tadalafil (killed on
      day 4), group 6: saline + tadalafil (killed on day 2) and group 7: saline +
      tadalafil (killed on day 4). The three different parts of basilar artery
      diameters were measured angiographically. RESULTS: There were statistically
      significant differences between the SAH and SAH groups treated with tadalafil at
      days 2 and 4. Comparison between control and tadalafil groups showed no
      significant differences. This result indicated that tadalafil has a vasodilatory
      effect on vasoconstricted arteries, but no effect on normal basilar arteries.
      CONCLUSION: Our study results showed that tadalafil has a vasodilatory effect on
      both acute and chronic periods of cerebral vasospasm. We also concluded that
      cerebral angiography can be used safely for investigation of cerebral vasospasm
      in animal studies.

PMID- 19841857
TI  - Training chart in movement disorders surgery added competence: as approved by the
      ESSFN and UEMS Section of Neurosurgery (March 2009).

PMID- 19841858
TI  - The VP5 protein of infectious bursal disease virus promotes virion release from
      infected cells and is not involved in cell death.
AB  - The VP5 protein of infectious bursal disease virus (IBDV) was shown in previous
      reports to be involved in the cytopathogenicity of IBDV. Here, using a rescued
      VP5-deficient IBDV infectious clone, it was demonstrated that a lack of VP5
      expression significantly hinders the release of viral progeny from infected cells
      but does not block intracellular virus production. Monoclonal VP5-expressing Vero
      cells did not exhibit induction of cell death. Using VP5-specific mAbs generated
      in our laboratory as a tool, it was shown by flow cytometry analysis that VP5 was
      detectable on the surface of IBDV-infected and monoclonal VP5-expressing Vero
      cells and bursal cells in IBDV-infected chickens. Taken together, these data
      suggest that the VP5 protein is involved in regulation of the release of
      intracellular IBDV virions and may be used as a cell-surface marker for detecting
      IBDV-infected cells in FCM analysis. This study contributes to the further
      characterization of the VP5 protein, which will allow a better understanding of
      the mechanism of IBDV pathogenicity.

PMID- 19841859
TI  - Repeated detection of European bat lyssavirus type 2 in dead bats found at a
      single roost site in the UK.
AB  - In August 2007, European bat lyssavirus type 2 (EBLV-2) was isolated from a
      Daubenton's bat found at Stokesay Castle. In September 2008, another bat from the
      same vicinity of Stokesay Castle also tested positive for EBLV-2. This is the
      first occurrence of repeated detection of EBLV-2 from a single site. Here, we
      report the detection of low levels of viral RNA in various bat organs by qRT-PCR
      and detection of viral antigen by immunohistochemistry. We also report sequence
      data from both cases and compare data with those derived from other EBLV-2
      isolations in the UK.

PMID- 19841860
TI  - Serum homocysteine, folate and vitamin B12 in patients with Paget's disease of
      bone: the effect of zoledronic acid.
AB  - High serum homocysteine (HCY) and indirectly deficiency of folate and/or vitamin
      B(12) stimulate bone resorption and adversely affect collagen cross-linking. The
      aim of this study was the evaluation of serum levels of HCY, folate and vitamin
      B(12) in patients with Paget's disease of bone (PDB) and the effect of zoledronic
      acid (ZOL) on their serum levels. Nine consecutive patients with polyostotic PDB
      (median age 66 years) received a single 5-mg ZOL infusion. Blood samples for HCY,
      folate, vitamin B(12), 25-hydroxyvitamin D (25-OH-D), total serum alkaline
      phosphatase (TSAP), bone-specific serum alkaline phosphatase (BSAP) and C
      terminal cross-linking telopeptide of type I collagen (CTX) were obtained at
      baseline and 3, 6 and 12 months after ZOL infusion. Twelve age-, gender- and BMI
      matched healthy individuals were recruited for the control group at baseline
      assessment. Patients with PDB had significantly higher serum HCY (p = 0.028),
      folate (p < 0.001) and bone markers [TSAP (p < 0.001), BSAP (p < 0.001) and CTX
      (p < 0.001)] compared with the control group at baseline. In the pagetic group,
      serum HCY significantly decreased 3 months after ZOL infusion and remained
      essentially unchanged up to the end of the study (p = 0.005). Serum vitamin B(12)
      and folate remained unaffected throughout the study. Our data suggest that serum
      HCY levels are increased in patients with PDB. A single ZOL infusion results in a
      decrease in HCY levels that might represent another mechanism for the reduction
      of the activity of PDB achieved by ZOL.

PMID- 19841862
TI  - Ultrasonographic evaluation of plantar fasciitis after low-level  laser therapy:
      results of a double-blind, randomized,  placebo-controlled trial.
AB  - The aim of this study was to investigate the effect of low-level laser therapy
      (LLLT) on plantar fasciitis documented by the ultrasonographic appearance of the
      aponeurosis and by patients' pain scores. Thirty individuals with diagnosis of
      unilateral plantar fasciitis were enrolled in a randomized, double-blind, placebo
      controlled trial, but 25 participants completed the therapeutic protocol. The
      contralateral asymptomatic fascia was used as control. After enrolment,
      symptomatic individuals were randomly assigned to receive LLLT, or identical
      placebo, for 6 weeks. Ultrasonography was performed at baseline and after
      completion of therapy. The subjective subcalcaneal pain was recorded at baseline
      and after treatment on a visual analogue scale (VAS). After LLLT, plantar fascia
      thickness in both groups showed significant change over the experimental period
      and there was a difference (before treatment and after treatment) in plantar
      fascia thickness between the two groups. However, plantar fascia thickness was
      insignificant (mean 3.627 +/- 0.977 mm) when compared with that in the placebo
      group (mean 4.380 +/- 1.0042 mm). Pain estimation on the visual analogue scale
      had improved significantly in all test situations (after night rest, daily
      activities) after LLLT when compared with that of the placebo group. (P=0.006 and
      P=0.01, respectively). Additionally, when the difference in pain scores was
      compared between the two groups, the change was statistically significant (after
      night rest P=0.000; daily activities P=0.001). In summary, while ultrasound
      imaging is able to depict the morphologic changes related to plantar fasciitis,
      904 nm gallium-arsenide (GaAs) infrared laser may contribute to healing and pain
      reduction in plantar fasciitis.

PMID- 19841861
TI  - The relationships among bone health, insulin-like growth factor-1 and sex
      hormones in adolescent female athletes.
AB  - The aim of this study was to determine the relationships of bone mineral density
      (BMD) and content (BMC) with insulin-like growth factor-1 (IGF-1), IGF-binding
      protein-3 (IGFBP-3) and estradiol in pubertal female athletes. The participants
      were 170 healthy adolescent girls (13-15 years) who participated in competitive
      extramural athletic programs, i.e., sports games (n = 49), track sprinting (n =
      24), rhythmic gymnastics (n = 23), swimming (n = 24) and cross-country skiing (n
      = 17). The control group (n = 33) consisted of girls who took part only in
      compulsory physical education classes at school. The whole-body BMD and femoral
      neck and lumbar spine BMD and BMC were measured using DXA, and the volumetric BMD
      was calculated. Venous blood samples to determine the concentration of IGF-1,
      IGFBP-3 and estradiol were drawn after an overnight fasting. After adjusting for
      age, body height and body mass, the relationships among BMD variables, IGF-1 and
      the IGF-1/IGFBP-3 molar ratio remained significant only in the rhythmic gymnast
      group. BMDs at the femoral neck and lumbar spine were also related to estradiol
      levels (r = 0.45-0.60; p < 0.05) only in the rhythmic gymnast group. No
      relationships were found among the measured BMD, IGF axis and estradiol in other
      athletic groups. Only BMC at the femoral neck remained associated with the IGF
      1/IGFBP-3 molar ratio in the rhythmic gymnast group after adjusting for age, body
      height and body mass. Stepwise multiple regression analysis indicated that IGF-1
      and estradiol together explained 42.6% (R(2) x 100) of total variance in the
      femoral neck BMD and IGF-1 alone 35.4% (R(2) x 100) of the total variance in the
      femoral neck BMC only in the rhythmic gymnast group. We conclude that femoral
      neck and lumbar spine BMD correlated with IGF-1, IGF-1/IGFBP-3 molar ratio and
      estradiol in rhythmic gymnasts. No relationships were found between bone
      parameters and the hormones used in other athletic groups.

PMID- 19841863
TI  - Headache and cognitive profile in children: a cross-sectional controlled study.
AB  - We investigated whether children affected by tension-type headache and migraine
      without aura, compared with a healthy control group that was matched by age,
      culturally and socioeconomically display a diverse intellectual functioning and
      have a separate "cognitive profile". A cross-sectional study was conducted from
      January 2006 to November 2008 at "Sapienza University" in Rome. A total of 134
      children were diagnosed as being affected by either migraine without aura (93) or
      tension-type headache (41). On the basis of our exclusion/inclusion criteria, we
      enrolled 82 of these 134 children, 63 of whom were affected by migraine without
      aura and 19 by tension-type headache. On entry, cognitive functions were assessed
      in both the affected subjects and the control group by the Wechsler Intelligence
      Scale for Children-revised. Significant differences were found between the
      headache and control groups in the mean total intelligence quotient and verbal
      intelligence quotient scores (p < 0.001). Significant negative correlations were
      found between the total intelligence quotient, verbal intelligence quotient,
      performance intelligence quotient and the frequency of attacks (r = -0.55 and p <
      0.001, r = -0.61 and p < 0.001, r = -0.29 and p < 0.01, respectively), as well as
      between the total intelligence quotient score and the age at headache onset (r =
      0.234, p < 0.05). Our results suggest that the cognitive profile of children
      affected by headache should be assessed at the first child neurology outpatient
      observation. From a therapeutic point of view, although within a normal range,
      the abilities most likely to be less brilliant in such children are verbal
      skills.

PMID- 19841864
TI  - Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status.
AB  - This retrospective series explores temozolomide monotherapy in elderly patients
      with primary CNS lymphoma (PCNSL) and severe comorbidities. In 17 patients (62-90
      years old), the complete response rate was 47%, median progression-free survival
      was 5 months, and median overall survival was 21 months. Five of 17 patients
      (29.4%) had prolonged responses for at least 12 months and survived for more than
      24 months. Three of these patients had a methylated O(6)-methylguanine-DNA
      methyltransferase (MGMT) promoter, while the MGMT status was not assessable in
      the remaining two patients. Temozolomide monotherapy appears to be effective in a
      subgroup of elderly PCNSL patients and deserves further evaluation.

PMID- 19841865
TI  - Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma
      patients, assessed by five different methods.
AB  - This multicenter study assesses the value of O(6)-methylguanine-DNA
      methyltransferase (MGMT) status for predicting overall survival in glioblastoma
      patients. Five methods are used, to identify the approach with the best
      prognostic value. Eighty-one tumors were obtained from patients with
      glioblastomas treated by surgery and radiotherapy with concomitant temozolomide
      (TMZ) followed by adjuvant TMZ. MGMT promoter methylation was assessed by
      qualitative methyl-specific polymerase chain reaction (MSP), semiquantitative
      methyl-specific polymerase chain reaction (SQ-MSP), and pyrosequencing, while
      MGMT expression was measured at the RNA level by quantitative real-time PCR (Q-RT
      PCR) and at the protein level by immunohistochemistry (IHC). MGMT promoter
      methylation as evaluated by MSP, SQ-MSP, and pyrosequencing was significantly
      correlated with overall survival. The best predictive value was obtained by
      pyrosequencing of one specific CpG position. Overall survival was 14 and 25
      months for patients with percentages of methylation below and above the median,
      respectively. In contrast, MGMT status determined by Q-RT-PCR and IHC showed
      little or no correlation with overall survival, respectively. These results
      confirm the prognostic value of MGMT promoter methylation in glioblastoma
      patients initially treated with TMZ. SQ-MSP allowed better discrimination than
      classical MSP, and pyrosequencing represented a good option.

PMID- 19841866
TI  - Changes in the level of apoptosis-related proteins in Jurkat cells infected with
      HIV-1 versus HIV-2.
AB  - Human immunodeficiency virus (HIV) infection-induced apoptosis of infected CD4 T
      cells as well as uninfected (bystander) CD4 T cells and other types of cells is a
      major factor in the pathogenesis of AIDS. Clinically, HIV-2 patients have a
      higher CD4 cell count at the time of an AIDS diagnosis, and generally have longer
      survival after development of symptoms. The mortality after an AIDS diagnosis has
      been reported to be more influenced by CD4 cell count than HIV type. Previous
      studies have shown significant variations in cytopathic effects following in
      vitro infection with primary isolates of HIV-1 or HIV-2 subtypes; however, the
      relative contributions of HIV-1 and HIV-2 infection leading to cell death remain
      unclear. Using a human cell line, Jurkat, we examined differences in key
      molecules involved in apoptotic signaling pathways during infection with either
      HIV-1 or HIV-2. HIV-1 infection generated more reactive oxygen species (ROS),
      increased the expression of a larger number of molecules involved in cell
      signaling such as p47, p38alpha, JNK, c-Yes, total PKC, and decreased the
      expression of molecules such as p38beta, ERK1/2, and XIAP relative to HIV-2
      infection. HIV-1 induced a higher degree of cell death through stronger
      activation of both apoptotic pathways. HIV-1 infection downregulated both Bcl
      X(L) and FLIP expressions at later time points postinfection, while HIV-2
      infection dramatically upregulated both Bcl-X(L) and FLIP expression. We also
      found that the expression of Bcl-X(L) or FLIP resulted in significant inhibition
      of HIV replication in Jurkat cells. These findings suggest that HIV-1 infection
      with high levels of cytotoxicity results in a higher level of cell death through
      apoptosis during a short time postinfection. The longer period of infection
      observed with HIV-2 with a lower degree of cytotoxicity was accompanied by
      increased Bcl-X(L) and FLIP expression. High protein levels of Bcl-X(L) or FLIP
      inhibit HIV replication and may be one explanation for the clinical observation
      that HIV-2 infected patients generally tend to be long-term nonprogressors with
      high CD4 lymphocyte counts compared with HIV-1 infected persons.

PMID- 19841867
TI  - MUC5AC production is downregulated in NCI-H292 lung cancer cells cultured on type
      IV collagen.
AB  - Mucus overproduction is an important feature of bronchial asthma. MUC5AC mucin is
      a major component of mucus and is overproduced in patients with asthma. Although
      regulation of MUC5AC production has been well investigated, its regulation
      through the signals from extracellular matrix (ECM) is less clear. In this study,
      we investigated whether the signals from ECM regulate MUC5AC production in the
      human lung epithelial cell line NCI-H292. We found that MUC5AC production is
      downregulated in NCI-H292 cells cultured on type-IV collagen, a major component
      of ECM, but shows no obvious changes when cultured on type-I collagen or
      fibronectin. In contrast, MUC5AC production was upregulated on laminin and on
      reconstituted basement membrane (Matrigel), a complex of ECM components. Antibody
      mediated inhibition of integrin beta1-subunit, a major receptor involved in the
      adherence of cells to type-IV collagen, upregulated the MUC5AC production in NCI
      H292 cells, and also in the cells cultured on type-IV collagen. Although the
      major signaling pathway from integrins is via Src kinase activation, treatment of
      cells with PP2, a Src kinase inhibitor, did not recover the downregulation of
      MUC5AC on type-IV collagen. In contrast, on Matrigel, the inhibition of integrin
      beta1-subunit did not abolish the upregulation of MUC5AC production, but PP2
      reduced the upregulation. These results suggest that ECM and an integrin/Src
      pathway play an important role in the regulation of MUC5AC production in the cell
      line NCI-H292. The production of MUC5AC is downregulated on type-IV collagen
      through a Src-independent pathway. In contrast, MUC5AC is upregulated on Matrigel
      through a Src-dependent pathway in NCI-H292 cells.

PMID- 19841868
TI  - Cloning of a novel lipase gene, lipJ08, from Candida rugosa and expression in
      Pichia pastoris by codon optimization.
AB  - A novel lipase gene, lipJ08, was cloned from Candida rugosa ATCC14830, along with
      the already reported five lipase genes (lip1-lip5). Nucleotide sequencing
      indicated that the lipJ08 gene contains a 1650 bp open reading frame (ORF)
      without introns. The deduced amino acid sequence corresponds to 534 amino acid
      residues, including a putative signal sequence of 15 amino acid residues.
      Seventeen of the non-universal serine codons (CTG) of lipJ08 were converted into
      universal serine codons (TCT) by PCR-based mutagenesis. The native and codon
      optimized lipJ08 genes were expressed in Pichia pastoris. The hydrolytic activity
      of the recombinant LIPJ08 was 4.7 U/ml, whereas the activity of the recombinant
      wild-type lipase could not be detected.

PMID- 19841869
TI  - Effects of manganese deficiency on spectral characteristics and oxygen evolution
      in maize chloroplasts.
AB  - The effects of Mn(2+) deficiency on light absorption, transmission, and oxygen
      evolution of maize chloroplasts were investigated by spectral methods. Several
      effects of Mn(2+) deficiency were observed: (1) the skeleton of pigment protein
      complexes and oxygen-evolving center and the combination between pigment and
      protein were damaged; (2) the light absorption of chloroplasts was obviously
      decreased; (3) the energy transfer among amino acids within PS II protein-pigment
      complex and decreased energy transport from tyrosine residue to chlorophyll a and
      from chlorophyll b and carotenoid to chlorophyll a were inhibited; (4) the oxygen
      evolving of chloroplast was significantly inhibited. However, Mn(2+) addition
      decreased the damage of light absorption, transmission, and oxygen evolution of
      maize chloroplasts caused by Mn(2+) deficiency.

PMID- 19841870
TI  - Interaction between nanoparticulate anatase TiO2 and lactate dehydrogenase.
AB  - In order to study the mechanisms underlying the effects of TiO(2) nanoparticles
      on lactate dehydrogenase (LDH, EC1.1.1.27), Institute of Cancer Research region
      mice were injected with nanoparticulate anatase TiO(2) (5 nm) of various doses
      into the abdominal cavity daily for 14 days. We then examined LDH activity in
      vivo and in vitro and direct evident for interaction between nanoparticulate
      anatase TiO(2) and LDH using spectral methods. The results showed that
      nanoparticulate anatase TiO(2) could significantly activate LDH in vivo and in
      vitro; the kinetics constant (Km) and Vmax were 0.006 microM and 1,149 unit mg(
      1) protein min(-1), respectively, at a low concentration of nanoparticulate
      anatase TiO(2), and 3.45 and 0.031 microM and 221 unit mg(-1) protein min(-1),
      respectively, at a high concentration of nanoparticulate anatase TiO(2). By
      fluorescence spectral assays, the nanoparticulate anatase TiO(2) was determined
      to be directly bound to LDH, and the binding constants of the binding site were
      1.77 x 10(8) L mol(-1) and 2.15 x 10(7) L mol(-1), respectively, and the binding
      distance between nanoparticulate anatase TiO(2) and the Trp residue of LDH was
      4.18 nm, and nanoparticulate anatase TiO(2) induced the protein unfolding. It was
      concluded that the binding of nanoparticulate anatase TiO(2) altered LDH
      structure and function.

PMID- 19841872
TI  - Spectroscopic behavior and biological activity of K2[VO(O2)NTA].2H2O.
AB  - The dihydrated potassium salt of the complex anion [VO(O(2))NTA](2-) (NTA =
      nitrilotriacetate anion, [N(CH(2)-COO)(3)](3-)) was thoroughly characterized by
      electronic and vibrational (infrared and Raman) spectroscopies. The bioactivity
      of the complex on the cell proliferation was tested on three cell lines in
      culture (UMR106 rat osteosarcoma-derived cells, Caco-2 derived from a human colon
      adenocarcinoma, and RAW 264.7, a macrophage murine cell line).

PMID- 19841873
TI  - The mechanism of CeCl3 on the activiation of alanine aminotransferase from mice.
AB  - The activity of alanine aminotransferase (ALT; E.C. 2.6.1.2) is often changed
      upon inflammatory responses in animals. Rare earths was shown to provoke various
      inflammatory responses both in rats and mice; however, the molecular mechanism by
      which rare earths exert its toxicity has not been completely understood,
      especially, we know little about the mechanism of the interaction between CeCl(3)
      and ALT. In this report, we investigated the mechanisms of CeCl(3) on ALT
      activity in vivo and in vitro. Our results showed that Ce(3+) could significantly
      activate ALT in vivo and in vitro; the kinetics constant (Km) and Vmax were 0.018
      microM and 1,380 unit mg(-1) protein min(-1), respectively, at a low
      concentration of Ce(3+), and 0.027 microM and 624 unit mg(-1) protein min(-1),
      respectively, at a high concentration of Ce(3+). By UV absorption and
      fluorescence spectroscopy assays, the Ce(3+) was determined to be directly bound
      to ALT; the binding site of Ce(3+) to ALT was 1.72, and the binding constants of
      the binding site were 4.82 x 10(8) and 9.05 x 10(7) L mol(-1). Based on the
      analysis of the circular dichroism spectra, it was concluded that the binding of
      Ce(3+) altered the secondary structure of ALT, suggesting that the observed
      enhancement of ALT activity was caused by a subtle structural change in the
      active site through the formation of the complex with Ce(3+).

PMID- 19841874
TI  - Needs and obstacles of uniform immunisation schedules in the European Union.
AB  - Immunisation schedules are developed by national committees on immunisation and
      may differ considerably between the European Union (EU) member states (MS). The
      European Commission has launched an initiative for a council recommendation with
      the aim to establish a scientifically substantiated reference childhood
      immunisation schedule for the EU. In our view this initiative implies the
      establishment of one European childhood immunisation schedule, which could lead
      to the perception that this schedule is the only one scientifically justified.
      The expectations that one uniform immunisation schedule will facilitate mobility
      of EU residents, improve data collection and increase vaccination coverage are
      either quantitatively or qualitatively not relevant or even ethically
      problematic. Arguments that uniform schedules would lead to lower vaccine prices
      and reduce the need for clinical trials appear to be more relevant but could be
      addressed more effectively by other measures. On the other hand the following
      factors may differ substantially between MS and thus support different
      immunisation schedules, such as (a) values and goals, (b) epidemiological
      situation, (c) health care delivery system, (d) logistics of vaccine delivery and
      (e) economic situation. We argue that uniform schedules should not be perceived
      as a goal in itself but rather as a possibly desired by-product following
      increasing agreement on goals and values between MS and improved evidence base to
      be used by national committees on immunisation.

PMID- 19841875
TI  - Polymorphisms of the lamina maturation pathway and their association with the
      metabolic syndrome: the DESIR prospective study.
AB  - Laminopathies are rare monogenic diseases, some of them exhibiting features of
      the metabolic syndrome. These diseases are mainly due to mutations in LMNA,
      encoding A-type lamins. One LMNA polymorphism, rs4641, has been associated with
      the metabolic syndrome, but results have been controversial. We therefore
      investigated the effect of single nucleotide polymorphisms (SNPs) in the LMNA
      gene in combination with four other genes encoding enzymes influencing lamin post
      translational maturation on risk of metabolic syndrome (MS). Twenty-three tagging
      SNPs characterising the haplotypic variability of five genes (LMNA, ICMT,
      ZMPSTE24, FNTA and FNTB) were genotyped in 3,916 French men and women who took
      part in the prospective DESIR study. Single locus and haplotype analyses were
      performed but did not detect any significant association with the risk of MS. No
      robust interaction between SNPs located in different genes on the risk of MS was
      identified. In conclusion, we did not observe any convincing evidence that common
      polymorphisms of the lamina pathway could modulate the risk of MS.

PMID- 19841878
TI  - Understanding how miRNAs post-transcriptionally regulate gene expression.
AB  - The discovery of microRNA (miRNA)-mediated gene silencing has added a new level
      of complexity to our understanding of post-transcriptional control of gene
      expression. Considering the ubiquity of miRNA-mediated repression throughout
      basic cellular processes, understanding its mechanism of action is paramount to
      obtain a clear picture of the regulation of gene expression in biological
      systems. Although many miRNAs and their targets have been identified, a detailed
      understanding of miRNA action remains elusive. miRNAs regulate gene expression at
      the post-transcriptional level, through both translational inhibition and mRNA
      destabilization. Recent reports suggest that many miRNA effects are mediated
      through proteins of the GW182 family. This chapter focuses on the multiple and
      potentially overlapping mechanisms that miRNAs utilize to regulate gene
      expression in eukaryotes.

PMID- 19841876
TI  - Stem cells--meet immunity.
AB  - The ability of stem cells to differentiate into various different cell types
      holds great promise for the treatment of irreversible tissue damage that occurs
      in many debilitating conditions. With stem cell research advancing at a
      tremendous pace, it is becoming clear that one of the greatest hurdles to
      successful stem cell-derived therapies is overcoming immune rejection of the
      transplant. Although the use of immunosuppressive drugs can decrease the
      incidence of acute graft rejection, the burden of problems associated with
      prolonged immunosuppression must be reduced. Strategies inducing specific
      immunological tolerance complemented by enhanced immune function will bring stem
      cell therapies closer to reality.

PMID- 19841877
TI  - Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and
      prevents the occurrence of diabetes in mice.
AB  - CD4(+)CD25(+) regulatory T cells (Treg), a subpopulation of CD4(+) T cells,
      regulate immune responses. Foxp3 is a key transcription factor for the
      development and function of Treg cells. During T-cell activation in vitro, a DNA
      demethylation agent 5-Aza-2'-deoxycytydine (DAC) can induce Foxp3 expression in
      CD4(+)CD25(-) Foxp3(-) cells via altering methylation status of a conserved
      element in the 5'-untranslated region of the Foxp3 gene. However, the effects of
      this agent on the development of Foxp3(+) Treg cells in the thymus and in vivo
      are poorly understood. In the present study, a short-term treatment with a low
      dose of DAC significantly increased the ratios of thymic CD4(+)CD8(-) CD25(+)
      cells or CD4(+)CD8(-) Foxp3(+) cells to CD4(+)CD8(-) cells, and the total numbers
      of thymic CD4(+)CD8(-)Foxp3(+) Treg cells or CD4(+)CD8(-)CD25(+)Foxp3(+) Treg
      cells in the thymus in mice. DAC-treatment induced the Foxp3 expression and the
      significant demethylation of a CpG island in the first intron of the Foxp3 gene
      in CD4(+)CD8(-)CD25(+) cells predominantly. Furthermore, CD4(+)CD8(-)CD25(+)
      thymocytes in DAC-treated mice exhibited enhanced immunosuppressive function than
      those in control mice. In addition, DAC treatment in vivo was effective in
      improving the clinical course of diabetes in cyclophosphamide (CY)-potentiated
      non-obese diabetic mice (CY-NOD). Thus, the in vivo treatment with DAC can
      significantly promote the development of natural thymic CD4(+)CD25(+)Foxp3(+)
      Treg cells through Foxp3 demethylation, implicating a therapeutic application of
      DAC in patients suffering from autoimmune diseases.

PMID- 19841879
TI  - Translational control of endogenous microRNA target genes in C. elegans.
AB  - lin-4 and let-7 are the founding members of the large microRNA (miRNA) family of
      regulatory RNAs and were originally identified as components of a C. elegans
      developmental pathway that controls temporal cell fates. Consistent with their
      pioneering role, lin-4 and let-7 were studied widely as "model miRNAs" in efforts
      to reveal the mode of action of miRNAs. Early work on lin-4 thus established a
      paradigm that miRNAs inhibit translation of their target mRNAs at a step
      downstream from initiation, without affecting mRNA stability. Although some
      studies on mammalian miRNAs in cell culture reached similar conclusions, most of
      those studies indicated that miRNAs repressed translation initiation and
      frequently also promoted target mRNA degradation. We will discuss here what is
      known about modes of miRNA target gene repression in C. elegans, highlighting
      recent work that demonstrates that both mRNA degradation and repression of
      translation initiation are mechanisms employed in vivo by let-7 and,
      unexpectedly, lin-4 to silence their endogenous targets. We will also discuss the
      roles of the GW182 homologous AIN-1 and AIN-2 proteins in this process.

PMID- 19841880
TI  - Translational inhibition by microRNAs in plants.
AB  - MicroRNAs (miRNAs) are 21-24 nucleotide riboregulators, which selectively repress
      gene expression through transcript cleavage and/or translational inhibition. It
      was thought that most plant miRNAs act through target transcript cleavage due to
      the high degree of complementarity between miRNAs and their targets. However,
      recent studies have suggested widespread translational inhibition by miRNAs in
      plants. The mechanisms underlining translational inhibition by plant miRNAs are
      largely unknown, but existing evidence has indicated that plants and animals
      share some mechanistic similarity of translational inhibition. Translational
      inhibition by miRNAs has been shown to regulate floral patterning, floral timing,
      and stress responses. This chapter covers recent progress on plant miRNA-mediated
      translational control.

PMID- 19841881
TI  - Regulation of p27(kip1) mRNA expression by microRNAs.
AB  - p27(kip1) (p27) is a cell cycle inhibitor and tumor suppressor whose expression
      is highly regulated in the cell. Low levels of p27 have been associated with poor
      prognosis in cancer. Recently, several microRNAs have been described to control
      p27 expression in various tumor types. In this chapter, we will provide an
      overview on the role of microRNAs in cancer, and will discuss how microRNAs
      regulate p27 expression and the implications for tumor progression.

PMID- 19841882
TI  - The inhibitory effect of apolipoprotein B mRNA-editing enzyme catalytic
      polypeptide-like 3G (APOBEC3G) and its family members on the activity of cellular
      microRNAs.
AB  - The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G
      or APOBEC3G) and its fellow cytidine deaminase family members are potent
      restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many
      other retroviruses. However, the cellular function of APOBEC3G remains to be
      further clarified. It has been reported that APOBEC3s can restrict the mobility
      of endogenous retroviruses and LTR-retrotransposons, suggesting that they can
      maintain stability in host genomes. However, APOBEC3G is normally cytoplasmic.
      Further studies have demonstrated that it is associated with an RNase-sensitive
      high molecular mass (HMM) and located in processing bodies (P-bodies) of
      replicating T-cells, indicating that the major cellular function of APOBEC3G
      seems to be related to P-body-related RNA processing and metabolism. As the
      function of P-body is closely related to miRNA activity, APOBEC3G could affect
      the miRNA function. Recent studies have demonstrated that APOBEC3G and its family
      members counteract miRNA-mediated repression of protein translation. Further,
      APOBEC3G enhances the association of miRNA-targeted mRNA with polysomes, and
      facilitates the dissociation of miRNA-targeted mRNA from P-bodies. As such,
      APOBEC3G regulate the activity of cellular miRNAs. Whether this function is
      related to its potent antiviral activity remains to be further determined.

PMID- 19841883
TI  - MicroRNA-mediated mRNA deadenylation and repression of protein synthesis in a
      mammalian cell-free system.
AB  - Cell-free systems are valuable tools for analyses of a post-transcriptional gene
      expression. The biochemical aspects of RNA interference have been extensively
      studied by using extracts prepared from Drosophila embryos. However, the
      mechanism by which microRNAs regulate protein synthesis is still elusive. We
      established a mammalian cell-free system that recapitulates let-7 microRNA
      mediated repression of protein synthesis. Using this system, we found that a
      target mRNA was deadenylated when it was translationally repressed. The
      experimental data strongly suggested that the deadenylation was a cause, but not
      a result, of translational repression. In this chapter, we describe our cell-free
      system and discuss the significance of microRNA-mediated mRNA deadenylation in
      the repression of protein synthesis.

PMID- 19841884
TI  - miRNA Effects on mRNA closed-loop formation during translation initiation.
AB  - A flurry of recent studies, carried out primarily in transfected cells or in
      vitro translation systems, have attempted to reveal the molecular means by which
      animal microRNAs (miRNAs) attenuate mRNA translation. Despite these intense
      efforts it has not yet been possible to derive a consensus model for such a
      mechanism. Here we summarise our own experimental contributions to this topic,
      which led us to propose that miRNAs control early translation initiation by
      affecting eukaryotic initiation factor 4E/cap structure and poly(A) tail
      function, and place them in a current context of this rapidly moving and
      challenging field.

PMID- 19841885
TI  - [Complementary medicine in oncology].
AB  - In cancer therapy vastly different kinds of treatment regimens, but as a rule
      scientifically validated and reviewed, play a central role dependent on the tumor
      entity. Besides the options of schoolbook medicine complementary, alternative and
      supportive treatment options are becoming more frequently used in routine
      clinical practice. Numerous concepts and agents, partly verified in studies and
      partly based on empirical experiences are being applied. It is our intention to
      give a survey of the most common agents and concepts and to point out the risks
      and capabilities.

PMID- 19841886
TI  - Identification and characterization of large-effect quantitative trait loci for
      grain yield under lowland drought stress in rice using bulk-segregant analysis.
AB  - An F(4:5) population of 490 recombinant inbred lines (RILs) from the cross
      Apo/(2*)Swarna was used to detect quantitative trait loci (QTL) with large
      effects on grain yield under drought stress using bulk-segregant analysis (BSA).
      Swarna is an important rainfed lowland rice variety grown on millions of hectares
      in Asia, but is highly susceptible to drought and aerobic soil conditions. Apo is
      an aerobic-adapted variety with moderate tolerance to drought. Two rice
      microsatellite (RM) markers, RM324, and RM416, located on chromosomes 2 and 3,
      respectively, were shown via BSA to be strongly associated with yield under
      lowland drought stress. The effects of these QTL were tested in a total of eight
      hydrological environments over a period of 3 years. The QTL linked to RM416
      (DTY(3.1)) had a large effect on grain yield under severe lowland drought stress,
      explaining about 31% of genetic variance for the trait (P < 0.0001). It also
      explained considerable variance for yield under mild stress in lowland conditions
      and aerobic environments. To our knowledge this is the first reported QTL that
      has a large effect on yield in both lowland drought and aerobic environments. The
      QTL linked to RM324 (DTY(2.1)) had a highly significant effect on grain yield in
      lowland drought stress (R(2) = 13-16%) and in two aerobic trials. The effect of
      these QTL on grain yield was verified to be not mainly due to phenology
      differences. Effects of DTY(3.1) on yield under stress have been observed in
      several other rice mapping populations studied at IRRI. Results of this study
      indicate that BSA is an effective method of identifying QTL alleles with large
      effects on rice yield under severe drought stress. The Apo alleles for these
      large-effect QTL for grain yield under drought and aerobic conditions may be
      immediately exploited in marker-assisted-breeding to improve the drought
      tolerance of Swarna.

PMID- 19841887
TI  - Accuracy of genotypic value predictions for marker-based selection in biparental
      plant populations.
AB  - The availability of cheap and abundant molecular markers has led to plant
      breeding methods that rely on the prediction of genotypic value from marker data,
      but published information is lacking on the accuracy of genotypic value
      predictions with empirical data in plants. Our objectives were to (1) determine
      the accuracy of genotypic value predictions from multiple linear regression (MLR)
      and genomewide selection via best linear unbiased prediction (BLUP) in biparental
      plant populations; (2) assess the accuracy of predictions for different numbers
      of markers (N(M)) and progenies (N(P)) used in estimation; and (3) determine if
      an empirical Bayes approach for modeling of the variances of individual markers
      and of epistatic effects leads to more accurate predictions in empirical data. We
      divided each of four maize (Zea mays L.) datasets, one Arabidopsis dataset, and
      two barley (Hordeum vulgare L.) datasets into an estimation set, where marker
      effects were calculated, and a test set, where genotypic values were predicted
      based on markers. Predictions were more accurate with BLUP than with MLR.
      Predictions became more accurate as N(P) and N(M) increased, until sufficient
      genome coverage was reached. Modeling marker variances with the empirical Bayes
      method sometimes led to slightly better predictions, but the accuracy with
      different variants of the empirical Bayes method was often inconsistent. In
      nearly all cases, the accuracy with BLUP was not significantly different from the
      highest accuracy across all methods. Accounting for epistasis in the empirical
      Bayes procedure led to poorer predictions. We concluded that among the methods
      considered, the quick and simple BLUP approach is the method of choice for
      predicting genotypic value in biparental plant populations.

PMID- 19841888
TI  - Using individual patient data in meta-analyses of glucose-lowering studies.

PMID- 19841889
TI  - Duration of diabetes, glucose control and cardiovascular risk.

PMID- 19841890
TI  - The interferon-induced helicase IFIH1 Ala946Thr polymorphism is associated with
      type 1 diabetes in both the high-incidence Finnish and the medium-incidence
      Hungarian populations.
AB  - AIMS/HYPOTHESIS: The rs1990760 polymorphism (Ala946Thr) of interferon induced
      with helicase C domain 1 (IFIH1) has been proposed to associate with type 1
      diabetes. In this study, association between IFIH1 Ala946Thr and type 1 diabetes
      was investigated in two distinct white populations, the Hungarians and Finns.
      METHODS: The rs1990760 polymorphism was genotyped in 757/509 Hungarian/Finnish
      childhood-onset cases, 499/250 Hungarian/Finnish control individuals and in
      529/924 Hungarian/Finnish nuclear family trios. Disease association was tested
      using case-control and family-based approaches. A meta-analysis of data from
      9,546 cases and 11,000 controls was also performed. RESULTS: In the Hungarian
      dataset, the A allele was significantly more frequent among cases than among
      controls (OR 1.29, 95% CI 1.10-1.52; p = 0.002). Combined analysis of Hungarian
      and Finnish datasets revealed a strong disease association (OR 1.235, 95% CI
      1.083-1.408; p = 0.002). Furthermore, the A allele was significantly
      overtransmitted in both family trio datasets (p = 0.017 in Hungarians; p = 0.007
      in Finns). The A allele was increased in Hungarian vs Finnish cases (64.9% vs
      60.8% in Finns; p = 0.003). The meta-analysis yielded a significant effect for
      IFIH1 rs1990760 A allele on type 1 diabetes risk (OR 1.176, 95% CI 1.130-1.225; p
      = 5.3 x 10(-15)) with significant heterogeneity between effect sizes across the
      studied populations (p = 0.023). CONCLUSIONS/INTERPRETATION: This study
      represents the first independent confirmation of the association between type 1
      diabetes and the IFIH1 gene in Hungarian and Finnish populations. Summarising the
      data published so far, a clear association between the Ala946Thr polymorphism and
      type 1 diabetes was detected, with an apparent difference in the contribution to
      disease susceptibility in different populations of European ancestry.

PMID- 19841891
TI  - Association of existing diabetes, gestational diabetes and glycosuria in
      pregnancy with macrosomia and offspring body mass index, waist and fat mass in
      later childhood: findings from a prospective pregnancy cohort.
AB  - AIMS/HYPOTHESIS: The aim of the study was to examine the association of existing
      diabetes (i.e. already diagnosed prior to pregnancy), gestational diabetes and
      glycosuria (both diagnosed and ascertained during pregnancy) with birthweight and
      future offspring BMI, waist circumference and fat mass (assessed by dual x-ray
      emission absorptiometry). METHODS: A prospective pregnancy/birth cohort study was
      performed using data from the Avon Longitudinal Study of Parents and Children.
      RESULTS: Among 10,591 mother-offspring pairs included in analyses with birth
      size, women with existing diabetes (n = 40), those diagnosed with gestational
      diabetes (n = 53) and those with at least two episodes of ++ glycosuria (n = 372)
      had greater mean birthweight and odds for macrosomia (birthweight > 4,000 g) than
      women with none of these. Adjusted odds ratios for macrosomia were 3.56 (95% CI
      1.53-8.28), 5.50 (95% CI 1.18-10.30) and 1.58 (95% CI 1.18-2.12) for existing
      diabetes, gestational diabetes and glycosuria, respectively. Among 6,842 mother
      offspring pairs with anthropometric measurements at age 9-11 years, maternal
      gestational diabetes and glycosuria (but not existing diabetes) were associated
      with increased offspring odds of general or central overweight/obesity. For
      gestational diabetes, these associations attenuated towards the null with
      adjustment for maternal prepregnancy BMI, but independent associations remained
      for glycosuria. The adjusted odds ratio for general overweight/obesity when
      comparing women with at least two episodes of ++ glycosuria with those with no
      evidence of diabetes or glycosuria was 1.35 (95% CI 1.00-1.82) and that for
      central obesity (top 10% waist circumference vs all others) was 1.31 (95% CI 1.00
      1.72). CONCLUSIONS/INTERPRETATION: These results provide some evidence for a long
      term effect of maternal glycaemia in pregnancy on offspring obesity risk.

PMID- 19841892
TI  - Short-form measures of diabetes-related emotional distress: the Problem Areas in
      Diabetes Scale (PAID)-5 and PAID-1.
AB  - AIMS/HYPOTHESIS: We wanted to identify a five-item short form of the Problem
      Areas in Diabetes Scale and a single-item measure for rapid screening of diabetes
      related emotional distress. METHODS: Using an existing database of 1,153 patients
      with diabetes, we conducted a principal-components analysis to identify a set of
      five items and then conducted a reliability analysis and validity checks. From
      those five items, we identified the item with the strongest psychometric
      properties as a one-item screening tool. RESULTS: We identified a reliable and
      valid short version of the Problem Areas in Diabetes Scale (PAID) comprising five
      of the emotional-distress questions of the full PAID items (PAID-5, with items 3,
      6, 12, 16, 19). The PAID-5 has satisfactory sensitivity (94%) and specificity
      (89%) for recognition of diabetes-related emotional distress. We also identified
      a one-item screening tool, the PAID-1 (Question 12: Worrying about the future and
      the possibility of serious complications), which has concurrent sensitivity and
      specificity of about 80% for the recognition of diabetes-related emotional
      distress. CONCLUSIONS/INTERPRETATION: The PAID-5 and PAID-1 appear to be
      psychometrically robust short-form measures of diabetes-related emotional
      distress.

PMID- 19841893
TI  - The ongoing H1N1 flu pandemic and the intensive care community: challenges,
      opportunities, and the duties of scientific societies and intensivists.

PMID- 19841894
TI  - Delayed colopericardial fistula and pyopneumopericardium.

PMID- 19841895
TI  - Early physiological and biological features in three animal models of induced
      acute lung injury.
AB  - INTRODUCTION: Critically ill patients often develop acute lung injury (ALI) in
      the context of different clinical conditions. We aimed to explore differences in
      early local and systemic features in three experimental animal models of ALI.
      METHODS: Mechanically ventilated male Sprague-Dawley rats were randomized to high
      tidal volume (VT) ventilation (HVT) (n = 8, VT 24 ml/kg), massive brain injury
      (MBI) (n = 8, VT 8 ml/kg) or endotoxemia (LPS) (n = 8, VT 8 ml/kg). Each
      experimental group had its own control group of eight rats (VT 8 ml/kg). We
      measured arterial blood gases, mean arterial pressure, lung compliance,
      inflammatory mediators in plasma and their expression and gelatinase activity in
      the lungs after 3 h of injury. RESULTS: Despite maintaining relatively normal
      lung function without evidence of important structural changes, we observed
      altered lung and systemic inflammatory responses in all three experimental
      models. LPS triggered the most robust inflammatory response and HVT the lowest
      systemic proinflammatory response. The HVT group had higher Il6, Tnf and Cxcl2
      mRNA in lungs than MBI animals. Metalloproteinase activity/expression and
      neutrophilic recruitment in the lungs were higher in HVT than in LPS or MBI.
      CONCLUSIONS: The early responses to direct or remote lung insult in our three
      models of ALI captured different physiological and biological features that could
      lead to respiratory and/or multiorgan failure.

PMID- 19841896
TI  - Prognostic factors in non-exertional heatstroke.
AB  - PURPOSE: To identify the prognostic factors associated with mortality in heat
      related illness. METHODS: Multi-center observational cohort-study in 16 emergency
      departments (ED) belonging to the teaching hospital network of the Paris area.
      The cohort comprised all patients admitted to one of the EDs during the August
      2003 heat wave in Paris and having a core temperature >38.5 degrees C. Baseline
      clinical and biological data in ED, patient's course and 1-year survival rate
      were recorded. Potential prognostic factors associated with death were assessed
      by Cox proportional-hazards analysis. RESULTS: A total of 1,456 patients were
      included. Mean age was 79 +/- 19 years. Critically ill conditions were noted in
      391 patients (27%), but only 72 (5%) were admitted into an intensive care unit.
      The survival rate was 57% at 1 year as compared to an expected 90% (P < 0.001).
      Nine independent prognostic factors were identified: previous treatment with
      diuretics, living in an institution, age >80 years, cardiac disease, cancer, core
      temperature >40 degrees C, systolic arterial pressure <100 mmHg, Glasgow coma
      scale <12 and transportation to hospital by ambulance. We defined three risk
      groups: low, intermediate and high risk, with a 1-year survival rate of 85, 61
      and 18%, respectively. CONCLUSIONS: We observed a low survival rate and developed
      a risk score based on easily obtained variables that may be useful to clinicians
      managing casualties from future heat waves.

PMID- 19841898
TI  - Do we need to know body anthropomorphic data whilst measuring abdominal pressure?

PMID- 19841897
TI  - The effects of vasopressin on acute kidney injury in septic shock.
AB  - OBJECTIVE: To compare the effects of vasopressin versus norepinephrine infusion
      on the outcome of kidney injury in septic shock. DESIGN AND SETTING: Post-hoc
      analysis of the multi-center double-blind randomized controlled trial of
      vasopressin versus norepinephrine in adult patients who had septic shock (VASST).
      PATIENTS AND INTERVENTION: Seven hundred seventy-eight patients were randomized
      to receive a blinded infusion of either low-dose vasopressin (0.01-0.03 U/min) or
      norepinephrine infusion (5-15 microg/min) in addition to open-label vasopressors
      and were included in the outcome analysis. All vasopressors were titrated and
      weaned to maintain a target blood pressure. MEASUREMENT AND RESULTS: RIFLE
      criteria for acute kidney injury were used to compare the effects of vasopressin
      versus norepinephrine. In view of multiple simultaneous comparisons, a p value of
      0.01 was considered statistically significant. Kidney injury was present in 464
      patients (59.6%) at study entry. In patients in the RIFLE "Risk" category (n =
      106), vasopressin as compared with norepinephrine was associated with a trend to
      a lower rate of progression to renal "Failure" or "Loss" categories (20.8 vs.
      39.6%, respectively, p = 0.03), and a lower rate of use of renal replacement
      therapy (17.0 vs. 37.7%, p = 0.02). Mortality rates in the "Risk" category
      patients treated with vasopressin compared to norepinephrine were 30.8 versus
      54.7%, p = 0.01, but this did not reach significance in a multiple logistic
      regression analysis (OR = 0.33, 99% CI 0.10-1.09, p = 0.02). The interaction of
      treatment group and RIFLE category was significant in predicting mortality.
      CONCLUSIONS: Vasopressin may reduce progression to renal failure and mortality in
      patients at risk of kidney injury who have septic shock.

PMID- 19841899
TI  - Why we need guidelines and recommendations for research on intra-abdominal
      hypertension.

PMID- 19841902
TI  - Comment on "Relationship between gas exchange response to prone position and lung
      recruitability during acute respiratory failure".

PMID- 19841903
TI  - Mixotrophic metabolism in Burkholderia kururiensis subsp. thiooxydans subsp.
      nov., a facultative chemolithoautotrophic thiosulfate oxidizing bacterium
      isolated from rhizosphere soil and proposal for classification of the type strain
      of Burkholderia kururiensis as Burkholderia kururiensis subsp. kururiensis subsp.
      nov.
AB  - A thiosulfate-oxidizing facultative chemolithoautotrophic Burkholderia sp. strain
      ATSB13(T) was previously isolated from rhizosphere soil of tobacco plant. Strain
      ATSB13(T) was aerobic, Gram-staining-negative, rod shaped and motile by means of
      sub-terminal flagellum. Strain ATSB13(T) exhibited mixotrophic growth in a medium
      containing thiosulfate plus acetate. A phylogenetic study based on 16S rRNA gene
      sequence analysis indicated that strain ATSB13(T) was most closely related to
      Burkholderia kururiensis KP23(T) (98.7%), Burkholderia tuberum STM678(T) (96.5%)
      and Burkholderia phymatum STM815(T) (96.4%). Chemotaxonomic data [G+C 64.0 mol%,
      major fatty acids, C(18:1) omega7c (28.22%), C(16:1) omega7c/15 iso 2OH (15.15%),
      and C(16:0) (14.91%) and Q-8 as predominant respiratory ubiquinone] supported the
      affiliation of the strain ATSB13(T) within the genus Burkholderia. Though the
      strain ATSB13(T) shared high 16S rRNA gene sequence similarity with the type
      strain of B. kururiensis but considerably distant from the latter in terms of
      several phenotypic and chemotaxonomic characteristics. DNA-DNA hybridization
      between strain ATSB13(T) and B. kururiensis KP23(T) was 100%, and hence, it is
      inferred that strain ATSB13(T) is a member of B. kururiensis. On the basis of
      data obtained from this study, we propose that B. kururiensis be subdivided into
      B. kururiensis subsp. kururiensis subsp. nov. (type strain KP23(T) = JCM 10599(T)
      = DSM 13646(T)) and B. kururiensis subsp. thiooxydans subsp. nov. (type strain
      ATSB13(T) = KACC 12758(T)).

PMID- 19841904
TI  - Administration of neurotoxic doses of MDMA reduces sensitivity to ethanol and
      increases GAT-1 immunoreactivity in mice striatum.
AB  - RATIONALE: Mice with reduced dopamine activity following neurotoxic doses of 3,4
      methylenedioxymethamphetamine (MDMA, 'ecstasy') consume more ethanol (EtOH) and
      show greater preference for EtOH. In keeping with human studies and other animal
      models where alcohol consumption and preference are also high, MDMA treatment
      will reduce sensitivity to certain physiological effects of EtOH. OBJECTIVE: We
      have examined the sensitivity to the acute effects of EtOH in MDMA-lesioned mice
      and the effects of EtOH on striatal gamma-aminobutyric acid (GABA) accumulation
      and expression of GABA subtype-1 transporter (GAT-1). METHODS: C57BL/6J mice were
      injected with neurotoxic MDMA (30 mg/kg, three times, every 3 h, i.p.). Seven
      days later, mice were given EtOH (3 g/kg, i.p.) to determine the loss of righting
      response and the development of rapid tolerance to the hypothermic effect of
      EtOH. The effect of EtOH on the striatal accumulation of GABA after inhibiting
      GABA transaminase and on GAT-1 immunoreactivity was also determined. RESULTS:
      Mice pre-treated with a neurotoxic dose of MDMA were less sensitive to the
      sedative-hypnotic effect of acute EtOH and exhibited alterations in the
      development of rapid tolerance to the hypothermic effect of EtOH. These animals
      showed an increase in striatal GAT-1 immunoreactivity. EtOH reduced GABA
      concentration in the striatum of non-lesioned mice, an effect not observed in
      MDMA-lesioned mice. CONCLUSION: These findings indicate that mice with a MDMA
      induced dopaminergic lesion show increased expression of striatal GAT-1 that may
      contribute to the lower sensitivity to EtOH-induced sedative effects and the
      resistance to the development of rapid tolerance to hypothermia produced by EtOH.

PMID- 19841905
TI  - Effect of acute and chronic treatment with milnacipran potentiates the
      anticonvulsant activity of conventional antiepileptic drugs in the maximal
      electroshock-induced seizures in mice.
AB  - RATIONALE: Depression often coexists with epilepsy. Simultaneous therapy of the
      two diseases may be associated with pharmacodynamic and/or pharmacokinetic
      interactions between antiepileptic and antidepressant drugs. OBJECTIVES: The aim
      of this study was to investigate the influence of acute and chronic treatment
      with intraperitoneal milnacipran (MLN), a selective serotonin/noradrenaline
      reuptake inhibitor, on the protective activity of valproate, carbamazepine (CBZ),
      phenytoin, or phenobarbital (PB) in the maximal electroshock (MES) test in mice.
      MATERIALS AND METHODS: Electroconvulsions were produced by an alternating current
      (50 Hz, 25 mA) delivered via ear-clip electrodes. Motor coordination and long
      term memory were evaluated in the chimney test and passive-avoidance task,
      respectively. Brain concentrations of antiepileptic drugs (AEDs) were assessed by
      immunofluorescence. RESULTS: Given acutely, MLN at 10 mg/kg increased the
      convulsive threshold. Acute MLN applied at the subprotective dose of 5 mg/kg
      enhanced the anticonvulsant effects of CBZ and PB. Chronic treatment with MLN (5
      30 mg/kg once daily for 2 weeks) did not affect either the electroconvulsive
      threshold or the anticonvulsant action of all studied conventional antiepileptic
      drugs. Since the antidepressant did not affect brain concentrations of
      antiepileptics used in the study, the revealed interactions seem to be of
      pharmacodynamic nature. Moreover, acute and chronic MLN, AEDs, and their
      combinations did not produce significant motor and long-term memory impairment.
      CONCLUSIONS: Acute, but not chronic, treatment with MLN can increase the
      effectiveness of some AEDs against MES-induced seizures in mice. It seems that
      MLN may also be considered as a candidate drug for clinical trials in patients
      with epilepsy and depressive disorders.

PMID- 19841906
TI  - Comparative study of five antiepileptic drugs on a translational cognitive
      measure in the rat: relationship to antiepileptic property.
AB  - RATIONALE: Antiepileptic drugs (AEDs) have been available for many years; yet,
      new members of this class continue to be identified and developed due to the
      limitations of existing drugs, which include a propensity for cognitive
      impairment. However, there is little preclinical information about the cognitive
      effects they produce, which clinically include deficits in attention and slowing
      of reaction time. OBJECTIVES: The purpose of this study was to profile two first
      generation AEDs, phenytoin and valproate, and three second-generation AEDs,
      levetiracetam, pregabalin and lacosamide. Initially, each drug was examined
      across a range of well characterised preclinical seizure tests, and then each
      drug was evaluated in the five-choice serial reaction time test (5-CSRTT) based
      on efficacious doses from the seizure tests. MATERIALS AND METHODS: Each AED was
      tested for anti-seizure efficacy in either (1) the maximal electroshock seizure
      test, (2) s.c. PTZ seizure test, (3) amygdala-kindled seizures and (4) the
      genetic absence epilepsy rat of Strasbourg model of absence seizures. On
      completion of these studies, each drug was tested in rats trained to asymptotic
      performance in the 5-CSRTT (0.5 s SD, 5 s ITI, 100 trials). Male rats were used
      in all studies. RESULTS: Each AED was active in at least one of the seizure
      tests, although only valproate was active in each test. In the 5-CSRT test, all
      drugs with the exception of levetiracetam, significantly slowed reaction time and
      increased omissions. Variable effects were seen on accuracy. The effect on
      omissions was reversed by increasing stimulus duration from 0.5 to 5 s,
      supporting a drug-induced attention deficit. Levetiracetam had no negative effect
      on performance; indeed, reaction time was slightly increased (i.e. faster).
      CONCLUSIONS: These results highlight somewhat similar effects of phenytoin,
      valproate, pregabalin and lacosamide on attention and reaction time, and
      comparison to efficacious doses from the seizure tests support the view that
      there may be a better separation with the newer AEDs. Levetiracetam had no
      detrimental effect in the 5-CSRTT, which may be consistent with clinical
      experience where the drug is considered to be well tolerated amongst the AED
      class.

PMID- 19841907
TI  - Spectroscopic characterization of bionanoparticles originating from newly
      developed self-forming synthetic PEGylated lipids (QuSomes).
AB  - In this work, we have aimed to merge the advantages of nanotechnology and
      biophotonics in conjunction with vibrational spectroscopic techniques in order to
      understand the various aspects of new kinds of synthetic bionanoparticles
      originating from self-forming synthetic biopolymers known as polyethylene glycol
      (PEG)ylated lipids. In particular, two complementary molecular spectroscopic
      techniques based on thin-layered Fourier transform infrared and confocal laser
      tweezers. Raman spectroscopy has been employed for the investigations of newly
      developed artificial PEGylated lipids trademarked as QuSomes. These novel types
      of synthetic lipids are composed of 1,2-dimyristoyl-rac-glycerol-3-dodecaethylene
      glycol (GDM-12), 1,2-dioleoyl-rac-glycerol-3-dodecaethylene glycol (GDO-12), and
      1,2-distearoyl-rac-glycerol-3-triicosaethylene glycol (GDS-23). The lipid labeled
      GDM-12 has saturated 14 acyl chains whereas GDO-12 is characterized by
      monounsaturated 18 acyl chains, and GDS-23 is composed of saturated 18 acyl
      chains in their hydrophobic chain. Similarly, GDM-12 and GDO-12 contain 12 units,
      and GDS-23 contains 23 units of hydrophilic PEG head groups. In contrast to
      conventional phospholipids, this novel kind of lipid can form liposomes
      spontaneously upon hydration, without the input of external activation energy. In
      addition, fluorescence correlation spectroscopy has been utilized to measure the
      size distribution of such nanoparticles in suspension as well as scanning
      electron microscopy has been applied for the imaging purposes. Although such
      PEGylated lipids show a common spectral pattern, important differences in the
      spectra have been observed, enabling us to distinguish these different lipids on
      the basis of characteristic features calculated from the spectroscopic band
      component analysis. Finally, in this study, detailed spectroscopic results due to
      the vibrational band assignments and band component analysis corresponding to
      various functional groups for individual nanoparticles have been analyzed and
      discussed.

PMID- 19841908
TI  - Sampling of benzene in environmental and exhaled air by solid-phase
      microextraction and analysis by gas chromatography-mass spectrometry.
AB  - Benzene is classified as a Group I carcinogen by the International Agency for
      Research on Cancer (IARC). The risk assessment for benzene can be performed by
      monitoring environmental and occupational air, as well as biological monitoring
      through biomarkers. The present work developed and validated methods for benzene
      analysis by GC/MS using SPME as the sampling technique for ambient air and
      breath. The results of the analysis of air in parks and avenues demonstrated a
      significant difference, with average values of 4.05 and 18.26 microg m(-3),
      respectively, for benzene. Sampling of air in the occupational environment
      furnished an average of 3.41 and 39.81 microg m(-3). Moreover, the correlations
      between ambient air and expired air showed a significant tendency to linearity (R
      (2) = 0.850 and R (2) = 0.879). The results obtained for two groups of employees
      (31.91 and 72.62 microg m(-3)) presented the same trend as that from the analysis
      of environmental air.

PMID- 19841909
TI  - Transmission electron microscopy characterization of colloidal copper
      nanoparticles and their chemical reactivity.
AB  - A colloidal synthesis method was developed to produce face centered cubic (fcc)
      Cu nanoparticles in the presence of surfactants in an organic solvent under an Ar
      environment. Various synthetic conditions were explored to control the size of
      the as-prepared nanoparticles by changing the precursor, varying the amount of
      surfactants, and tuning the reaction temperature. Transmission electron
      microscopy (TEM), selected-area electron diffraction, and high-resolution TEM
      were used as the main characterization tools. Upon exposure to air, these
      nanoparticles are oxidized at different levels depending on their sizes: (1) an
      inhomogeneous layer of fcc Cu(2)O forms at the surface of Cu nanoparticles (about
      30 nm); (2) Cu nanoparticles (about 5 nm) are immediately oxidized into fcc
      Cu(2)O nanoparticles (about 6 nm). The occurrence of these different levels of
      oxidization demonstrates the reactive nature of Cu nanoparticles and the effect
      of size on their reactivity. Furthermore, utilization of their chemical
      reactivity and conversion of spherical Cu nanoparticles into CuS nanoplates
      through the nanoscale Kirkendall effect were demonstrated. The oxidization and
      sulfidation of Cu nanoparticles were compared. Different diffusion and growth
      behaviors were involved in these two chemical transformations, resulting in the
      formation of isotropic Cu(2)O nanoparticles during oxidization and anisotropic
      CuS nanoplates during sulfidation.

PMID- 19841910
TI  - Determination of ganglioside composition and structure in human brain hemangioma
      by chip-based nanoelectrospray ionization tandem mass spectrometry.
AB  - We report here on a preliminary investigation of ganglioside composition and
      structure in human hemangioma, a benign tumor in the frontal cortex (HFC) in
      comparison to normal frontal cortex (NFC) tissue using for the first time
      advanced mass spectrometric methods based on fully automated chip
      nanoelectrospray (nanoESI) high-capacity ion trap (HCT) and collision-induced
      dissociation (CID). The high ionization efficiency, sensitivity and
      reproducibility provided by the chip-nanoESI approach allowed for a reliable MS
      based ganglioside comparative assay. Unlike NFC, ganglioside mixture extracted
      from HFC was found dominated by species of short glycan chains exhibiting lower
      overall sialic acid content. In HFC, only GT1 (d18:1/20:0), and GT3 (d18:1/25:1)
      polysialylated species were detected. Interestingly, none of these trisialylated
      forms was detected in NFC, suggesting that such components might selectively be
      associated with HFC. Unlike the case of previously investigated high malignancy
      gliosarcoma, in HFC one modified O-Ac-GD2 and one modified O-Ac-GM4 gangliosides
      were observed. This aspect suggests that these O-acetylated structures could be
      associated with cerebral tumors having reduced malignancy grade. Fragmentation
      analysis by CID in MS(2) mode using as precursors the ions corresponding to GT1
      (d18:1/20:0) and GD1 (d18:1/20:0) provided data corroborating for the first time
      the presence of the common GT1a and GT1b isomers and the incidence of unusual
      GT1c and GT1d glycoforms in brain hemangioma tumor.

PMID- 19841911
TI  - 3-MCPD in food other than soy sauce or hydrolysed vegetable protein (HVP).
AB  - This review gives an overview of current knowledge about 3-monochloropropane-1,2
      diol (3-MCPD) formation and detection. Although 3-MCPD is often mentioned with
      regard to soy sauce and acid-hydrolysed vegetable protein (HVP), and much
      research has been done in that area, the emphasis here is placed on other foods.
      This contaminant can be found in a great variety of foodstuffs and is difficult
      to avoid in our daily nutrition. Despite its low concentration in most foods, its
      carcinogenic properties are of general concern. Its formation is a multivariate
      problem influenced by factors such as heat, moisture and sugar/lipid content,
      depending on the type of food and respective processing employed. Understanding
      the formation of this contaminant in food is fundamental to not only preventing
      or reducing it, but also developing efficient analytical methods of detecting it.
      Considering the differences between 3-MCPD-containing foods, and the need to test
      for the contaminant at different levels of food processing, one would expect a
      variety of analytical approaches. In this review, an attempt is made to provide
      an up-to-date list of available analytical methods and to highlight the
      differences among these techniques. Finally, the emergence of 3-MCPD esters and
      analytical techniques for them are also discussed here, although they are not the
      main focus of this review.

PMID- 19841912
TI  - Characterization of polyadenylated cryIA(b) transcripts in maize MON810
      commercial varieties.
AB  - The Zea mays L. event MON810 is one of the major commercialized genetically
      modified crops. The inserted expression cassette has a 3' truncation partially
      affecting the cryIA(b) coding sequence, resulting in the lack of the NOS
      terminator, with transcription of the transgene reported to read-through 3'-past
      the truncation site. Here, we demonstrate that the cryIA(b) transgene gives rise
      to a variety of polyadenylated transcripts of different sizes that extend to
      around 1 kbp downstream the truncation site. A Stop codon at position +7
      downstream the truncation site indicates the production of a transgenic protein
      with two additional amino acids; which is compatible with the reported size of
      the CryIA(b) protein in MON810. There is no evidence of the existence of other
      translated products. Several main 3' transcription termination regions were
      detected close to the truncation site and in the transgene 3' flanking sequence.
      Next to these main termination sites, we identified some sequence motifs that
      could potentially act as 3'-end-processing elements and drive termination of the
      transgene transcripts. The MON810 transgene has been introduced into different
      commercial varieties through breeding programs. Here, we demonstrate that there
      are no significant differences among the levels of transgene mRNA accumulation,
      major transcript sizes and 3' termini profiles comparing a number of MON810
      commercial varieties grown under similar environmental conditions. Commercial
      varieties of this event appear to be stable in terms of transgene expression.

PMID- 19841913
TI  - An optimal design method for preventing air bubbles in high-temperature
      microfluidic devices.
AB  - DNA analysis with the polymerase chain reaction (PCR) has become a routine part
      of medical diagnostics, environmental inspections, food evaluations, and
      biological studies. Furthermore, the development of a microscale PCR chip is an
      essential component of studies aimed at integrating PCR into a micro total
      analysis system (mu-TAS). However, the occurrence of air bubbles in microchannels
      complicates this process. In this study, we investigated a new technique based on
      the fluid dynamics of laminar flow that utilizes a small amount of mineral oil at
      the beginning of sample injection to prevent air bubbles from occurring in
      microchannels. We also further optimized the pressure, the length of the
      pressurizing channel and the volume of oil, thus making our microfluidic device
      more useful for high-temperature PCR. Additionally, quantitative continuous-flow
      PCR was performed using the optimized PCR chip in order to detect genetically
      modified (GM) maize. DNA was extracted from GM maize, MON 810, and non-GM maize
      at several concentrations from 0% (w/v) to 100% (w/v). The DNA amplification
      signals were then analyzed on the PCR chip using a laser-based system. The signal
      from our microfluidic PCR chip was found to increase in direct proportion to the
      initial GM maize concentration.

PMID- 19841914
TI  - Precision and accuracy of ocular following: influence of age and type of eye
      movement.
AB  - Previous work on ocular-following emphasises the accuracy of tracking eye
      movements. However, a more complete understanding of oculomotor control should
      account for variable error as well. We identify two forms of precision: 'shake',
      occurring over shorter timescales; 'drift', occurring over longer timescales. We
      show how these can be computed across a series of eye movements (e.g. a sequence
      of slow-phases or collection of pursuit trials) and then measure accuracy and
      precision for younger and older observers executing different types of eye
      movement. Overall, we found older observers were less accurate over a range of
      stimulus speeds and less precise at faster eye speeds. Accuracy declined more
      steeply for reflexive eye movements and shake was independent of speed. In all
      other instances, the two measures of precision expanded non-linearly with mean
      eye speed. We also found that shake during fixation was similar to shake for
      reflexive eye movement. The results suggest that deliberate and reflexive eye
      movement do not share a common non-linearity or a common noise source. The
      relationship of our data to previous studies is discussed, as are the
      consequences of imprecise eye movement for models of oculomotor control and
      perception during eye movement.

PMID- 19841915
TI  - Perception of risk regarding the use of medications and other exposures during
      pregnancy.
AB  - BACKGROUND: Perception of risk may impact a woman's decision to take a needed
      drug during pregnancy. There is a paucity of research on this topic in the
      literature. OBJECTIVES: (1) To evaluate the perception of risk of 17 commonly
      used drugs and other substances by pregnant women. (2) To investigate which
      sources of information regarding exposures during pregnancy were most commonly
      used by women. METHODS: A questionnaire was developed through the University of
      Oslo's website for Internet surveys and posted on four Web pages used by pregnant
      women and mothers, from mid-September 2008 through October 2008. The inclusion
      criteria included women who were (1) pregnant or 2) a mother of a child less than
      5 years old. RESULTS: A total of 1,793 eligible women completed the
      questionnaire. Most women overestimated the teratogenic risk associated with all
      the drugs during pregnancy. Characteristics of the women that were associated
      with a high perception of risk were primiparity, higher age, higher education,
      and choosing not to use a drug during pregnancy. More than 80% of the women had
      used drugs during pregnancy, mostly paracetamol, penicillins and reflux
      medications. The physician, the product information leaflet and the pharmacist
      were the three most frequently used sources of information. CONCLUSION: Women
      overestimate the risk of drug use and other exposures during pregnancy.
      Therefore, it is important for health care providers to use evidence-based
      information, to reduce unnecessary anxiety, and to ensure safe and appropriate
      treatment during pregnancy.

PMID- 19841917
TI  - Bioprospecting for microbial products that affect ice crystal formation and
      growth.
AB  - At low temperatures, some organisms produce proteins that affect ice nucleation,
      ice crystal structure, and/or the process of recrystallization. Based on their
      ice-interacting properties, these proteins provide an advantage to species that
      commonly experience the phase change from water to ice or rarely experience
      temperatures above the melting point. Substances that bind, inhibit or enhance,
      and control the size, shape, and growth of ice crystals could offer new
      possibilities for a number of agricultural, biomedical, and industrial
      applications. Since their discovery more than 40 years ago, ice nucleating and
      structuring proteins have been used in cryopreservation, frozen food preparation,
      transgenic crops, and even weather modification. Ice-interacting proteins have
      demonstrated commercial value in industrial applications; however, the full
      biotechnological potential of these products has yet to be fully realized. The
      Earth's cold biosphere contains an almost endless diversity of microorganisms to
      bioprospect for microbial compounds with novel ice-interacting properties.
      Microorganisms are the most appropriate biochemical factories to cost effectively
      produce ice nucleating and structuring proteins on large commercial scales.

PMID- 19841916
TI  - Perfusion MRI of brain tumours: a comparative study of pseudo-continuous arterial
      spin labelling and dynamic susceptibility contrast imaging.
AB  - INTRODUCTION: The purpose of this study was to compare the non-invasive 3D pseudo
      continuous arterial spin labelling (PC ASL) technique with the clinically
      established dynamic susceptibility contrast perfusion magnetic resonance imaging
      (DSC-MRI) for evaluation of brain tumours. METHODS: A prospective study of 28
      patients with contrast-enhancing brain tumours was performed at 3 T using DSC-MRI
      and PC ASL with whole-brain coverage. The visual qualitative evaluation of signal
      enhancement in tumour was scored from 0 to 3 (0 = no signal enhancement compared
      with white matter, 3 = pronounced signal enhancement with equal or higher signal
      intensity than in grey matter/basal ganglia). The extent of susceptibility
      artefacts in the tumour was scored from 0 to 2 (0 = no susceptibility artefacts
      and 2 = extensive susceptibility artefacts (maximum diameter > 2 cm)). A
      quantitative analysis was performed with normalised tumour blood flow values (ASL
      nTBF, DSC nTBF): mean value for region of interest (ROI) in an area with maximum
      signal enhancement/the mean value for ROIs in cerebellum. RESULTS: There was no
      difference in total visual score for signal enhancement between PC ASL and DSC
      relative cerebral blood flow (p = 0.12). ASL had a lower susceptibility-artefact
      score than DSC-MRI (p = 0.03). There was good correlation between DSC nTBF and
      ASL nTBF values with a correlation coefficient of 0.82. CONCLUSION: PC ASL is an
      alternative to DSC-MRI for the evaluation of perfusion in brain tumours. The
      method has fewer susceptibility artefacts than DSC-MRI and can be used in
      patients with renal failure because no contrast injection is needed.

PMID- 19841919
TI  - Reamed and unreamed intramedullary nailing for the treatment of open and closed
      tibial fractures: a subgroup analysis of randomised trials.
AB  - The choice between reamed and unreamed intramedullary nailing for the treatment
      of open and closed tibial fractures is an ongoing controversy. We carried out a
      comprehensive search strategy. Six eligible randomised controlled trials were
      included. Three reviewers independently assessed methodological quality and
      extracted outcome data. Analyses were performed using Review Manager 5.0. The
      results showed lower risks of tibial fracture nonunion and implant failures with
      reamed nails compared to unreamed nails in closed tibial fractures [relative risk
      (RR): 0.41, 95% confidence interval (CI): 0.21-0.89, P = 0.008 for nonunion and
      RR: 0.35, 95% CI: 0.22-0.56, P < 0.0001 for implant failures], but no statistical
      differences in risk reduction of malunion, compartment syndrome, embolism and
      infection. Our results suggested no statistical differences in risk reduction of
      all the complications evaluated between reamed and unreamed nails in open tibial
      fractures. In conclusion, our study recommended reamed nails for the treatment of
      closed tibial fractures. But the choice for open tibial fractures remains
      uncertain.

PMID- 19841920
TI  - Range of motion and function are similar in patients undergoing TKA with
      posterior stabilised and high-flexion inserts.
AB  - It is debatable whether high-flexion (HF) total knee arthroplasty (TKA) designs
      will improve postoperative flexion and function or will diminish the need for
      manipulation under anaesthesia (MUA). We retrospectively analysed range of motion
      (ROM), flexion, Knee Society Score (KSS), and rate of MUA in a consecutive group
      of patients who underwent TKA with a conventional posterior stabilised (PS)
      insert or an HF insert using identical surgical technique, implant design, and
      postoperative care. Fifty TKAs with a standard PS insert were matched for
      patient's age, gender, preoperative ROM, and KSS with 50 TKA performed with an HF
      insert. The patient's ROM and KSS were evaluated at six weeks, four months, and
      one year postoperatively. The outcome variables (flexion, ROM, KSS, and
      manipulation rate) in both groups were compared using the generalised estimating
      equations method. A second analysis of patients with preoperative flexion >=120
      degrees  was performed. The ROM, flexion, and patient-reported KSS was similar in
      both groups at each time period. The rate of MUA was also similar. Patients with
      a preoperative ROM of at least 120 degrees  showed similar results. Our study
      found that one year after surgery, patients who underwent TKA with a PS or an HF
      insert achieved similar flexion, ROM, and function.

PMID- 19841921
TI  - Vitamin D deficiency and anemia: a cross-sectional study.
AB  - Vitamin D has been suggested to have an effect on erythropoiesis. We sought to
      evaluate the prevalence of anemia in a population of individuals with vitamin D
      deficiency compared with those with normal levels in a population of a large
      integrated healthplan. A cross-sectional analysis in the period 1 January 2004
      through 31 December 2006 of subjects with documented concurrent levels of 25
      hydroxyvitamin D and hemoglobin were evaluated. Vitamin D deficiency was defined
      as <30 ng/mL and anemia was defined as a hemoglobin <11 g/dL. A total of 554
      subjects were included in the analysis. Anemia was present in 49% of 25
      hydroxyvitamin D-deficient subjects compared with 36% with normal 25
      hydroxyvitamin D levels (p < 0.01). Odds ratio for anemia in subjects with 25
      hydroxyvitamin D deficiency using logistic regressions and controlling for age,
      gender, and chronic kidney disease was 1.9 (95% CI 1.3-2.7). 25-hydroxyvitamin D
      deficient subjects had a lower mean Hb (11.0 vs. 11.7; p = 0.12 ) and a higher
      prevalence of erythrocyte stimulating agent use (47% vs. 24%; p < 0.05). This
      study demonstrates an association of vitamin D deficiency and a greater risk of
      anemia, lower mean hemoglobin, and higher usage of erythrocyte-stimulating
      agents. Future randomized studies are warranted to examine whether vitamin D
      directly affects erythropoiesis.

PMID- 19841922
TI  - Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects
      of co-administered anti-cancer agents.
AB  - PURPOSE: Pharmacokinetic/pharmacodynamic (PK/PD) models have been shown to be
      useful in predicting tumor growth rates in mouse xenografts. We applied novel
      PK/PD models to the published anticancer combination therapies of tumor growth
      inhibition to simulate synergistic changes in tumor growth rates. The parameters
      from the PK/PD model were further used to estimate clinical doses of the
      combination. METHODS: A PK/PD model was built that linked the dosing regimen of a
      compound to the inhibition of tumor growth in mouse xenograft models. Two
      subsequent PK/PD models were developed to simulate the published tumor growth
      profiles of combination treatments. Model I predicts the tumor growth curve
      assuming that the effect of two anticancer drugs, AZD7762 and irinotecan, is
      synergistic when given in combination. Model II predicts the tumor growth curve
      assuming that the effect of co-administering flavopiridol and irinotecan is
      maximally synergistic when dosed at an optimal interval. RESULTS: Model I was
      able to account for the synergistic effects of AZD7762 following the
      administration of irinotecan. When Model II was applied to the antitumor activity
      of irinotecan and flavopiridol combination therapy, the modeling was able to
      reproduce the optimal dosing interval between administrations of the compounds.
      Furthermore, Model II was able to estimate the biologically active dose of
      flavopiridol recommended for phase II studies. CONCLUSIONS: The timing of
      clinical combination therapy doses is often selected empirically. PK/PD models
      provide a theoretical structure useful in the design of the optimal clinical
      dose, frequency of administration and the optimal timing of administration
      between anticancer agents to maximize tumor suppression.

PMID- 19841923
TI  - Pediatric tracheostomy: complications and role of home care in a developing
      country.
AB  - INTRODUCTION: Tracheotomy in its earlier days was most commonly performed for
      acute airway infection in children. Its indications are now changing; it is now
      most commonly performed for congenital malformations (McMurray and Prescott in
      Practical pediatric otolaryngology. W.B. Saunders Company, Philadelphia, pp 575
      592, 1996). This shift in indication has increased the rate of survival of such
      patients, and therefore the number of children going home after tracheostomy has
      also increased. OBJECTIVE: This study was conducted (1) to observe the pattern of
      indication and complications for tracheostomy, in our part of the world, (2) the
      rate at which tracheostomy can help wean patients off the ventilator, and (3) the
      feasibility of sending these children home with tracheostomy. MATERIALS AND
      METHODS: A retrospective study was done on 127 patients. The indications, final
      outcome and the complications encountered in and outside the hospital were
      studied through review of charts. RESULTS: Based on the main indications,
      patients were grouped into: prolonged ventilation group (PV) 61%, followed by
      mechanical obstruction group (MO) 22%, and the last being adjunct to surgery
      group (AS) 17%. The in-hospital complication rate was 30% and that at home was
      18.11%. The most common complications included upper respiratory tract
      infections, and blockage or displacement of tubes. The late complication rate was
      4%. Hundred (78.8%) patients on the ventilator could be successfully weaned off,
      with a p value of 0.001; 81 were sent home with the tracheostomy tube (TT). Forty
      of these were successfully decannulated and the overall decannulation rate was
      48.8%. CONCLUSION: A large number of tracheostomies have been performed in the PV
      group to reduce the intensive care unit (ICU) stay and to prevent nosocomial
      infections. The need arises from the high cost of prolonged stay in an ICU setup,
      which is a cause of major economic burden, and lack of financial assistance for
      these patients worsens the scenario. Home care of the tracheostomy tubes remains
      a good option for patients requiring long periods of time to overcome their
      primary pathology.

PMID- 19841924
TI  - [Autoinflammatory diseases in childhood].
AB  - Autoinflammatory diseases are a group of monogenic inflammatory diseases with an
      early onset in childhood. Previously these diseases were summarized as"periodic
      fever syndromes." Included in this spectrum are familial Mediterranean fever,
      mevalonate kinase deficiency, and tumor necrosis factor receptor-associated
      disease. They are characterized by periodic or recurrent episodes of systemic
      inflammation causing fever, accompanied by rash, serositis, lymphadenopathy,
      arthritis, and other clinical manifestations. The other large group of
      autoinflammatory diseases consists of the cryopyrin-associated periodic
      syndromes, which include the cryopyrinopathies. The mildest form is familial cold
      associated syndrome, a more severe form is Muckle-Wells syndrome, and the most
      severe is neonatal-onset multisystem inflammatory disease/chronic infantile
      neurological cutaneous and articular syndrome. These are characterized by chronic
      or recurrent systemic inflammation associated with various clinical
      presentations, including urticaria-like rash, arthritis, sensorineural deafness,
      and central nervous system and bone involvement. In our review we focus on the
      clinical presentation of these diseases.

PMID- 19841925
TI  - Interscalene brachial plexus block for open-shoulder surgery: a randomized,
      double-blind, placebo-controlled trial between single-shot anesthesia and patient
      controlled catheter system.
AB  - INTRODUCTION: Interscalene brachial plexus block (ISB) is widely used as an
      adjuvant regional pain therapy in patients undergoing major shoulder surgery and
      has proved its effectiveness on postoperative pain reduction and opioid-sparing
      effect. METHOD: This single-center, prospective, double-blind, randomized and
      placebo-controlled study was to compare the effectiveness of a single-shot and a
      patient-controlled catheter insertion ISB system after major open-shoulder
      surgeries. Seventy patients were entered to receive an ISB and a patient
      controlled interscalene catheter. The catheter was inserted under ultrasound
      guidance. Patients were then assigned to receive one of two different
      postoperative infusions, either 0.2% ropivacaine (catheter group) or normal
      saline solution (single-shot group) via a disposable patient-controlled infusion
      pump. RESULTS: The study variables were amount of rescue medication, pain at rest
      and during physiotherapy, patient satisfaction and incidence of unwanted side
      effects. The ropivacaine group revealed significantly less consumption of rescue
      medication within the first 24 h after surgery. Incidence of side effects did not
      differ between the two groups. CONCLUSION: Based on our results, we recommend the
      use of interscalene plexus block in combination with a patient-controlled
      catheter system under ultrasound guidance only for the first 24 h after major
      open-shoulder surgery.

PMID- 19841926
TI  - Six-year follow-up of a preformed spacer for the management of chronically
      infected total hip arthroplasty.
AB  - Antibiotic-loaded cement spacers are currently used in two-stage revision of
      septic total hip arthroplasty as temporary devices. Prolonged spacer implantation
      in infected shoulder has been described occasionally in poor candidates for
      reconstruction surgery (medically compromised and/or low-physical demand
      patients, deficient bone stock). Few papers previously reported the use of
      spacers in infected hip prosthesis as a permanent solution, but limited
      information is available on the medium-term behaviour. We detail medium-term
      clinical and radiographic follow-up of a preformed spacer in the management of a
      chronically infected hip arthroplasty in a 50-year-old female patient who did not
      undergo a second-stage surgery. Normalization of inflammatory markers was
      detected 3 weeks after surgery and persisted over time. Six years after surgery,
      the patient recovered a good range of motion and was able to walk pain free with
      assisted weightbearing. Remarkable radiological changes of the bone stock around
      the spacer stem have been assessed. New bone formation developed rapidly in the
      femur, leading to the consolidation of transfemoral osteotomy 6 months
      postoperatively. Two years after implantation, spontaneous and asymptomatic
      fatigue fracture in the mid-part of the stem occurred. Radiographs at 6 years
      showed a sufficient preservation of bone stock, though a slowly progressive
      resorption of the cortical femur around the stem was evident in the last year. In
      conclusion, prolonged spacer implantation seems to be not appropriate in septic
      hip arthroplasty as a permanent solution. In patients not undergoing a second
      stage surgery, a careful and periodic monitoring is required to rule out possible
      and severe complications.

PMID- 19841928
TI  - Laparoscopic ureterolysis and dissection of the paravesical space for deeply
      scarred adnexal masses.
AB  - INTRODUCTION: Laparoscopic ureterolysis is a delicate procedure that requires
      advanced laparoscopic skills. MATERIALS AND METHODS: We are reporting two cases
      of laparoscopic hysterectomy and salpingo-oophorectomy with severe adhesions to
      the pelvic sidewall that required ureterolysis and describing a modified
      technique suitable for the laparoscopic performance of this procedure. RESULTS:
      In more than 15 years of doing laparoscopic ureterolysis to deal with various
      gynecological cases, we have never had a ureteral injury related to the
      ureterolysis procedure. There have been uterine artery lacerations, usually when
      trying to apply clips for uterine artery ligation in which case the artery can be
      compressed with a clamp until it is reclipped, bipolar-cauterized or suture
      ligated using intracorporeal knot tying. However, we did not have a single
      patient that required open surgery because of these lacerations. CONCLUSION:
      Because of the advantage of magnified viewing and laparoscopic dissection
      techniques which control small vessel bleeding, the laparoscopic route for
      ureterolysis is far easier to use than its open counterpart once it is learned.
      Laparoscopy, in addition, offers the added advantages of shorter hospital stay,
      reduced patient pain, reduced transfusion requirements and far better cosmetic
      results.

PMID- 19841929
TI  - Cancer mortality among German aircrew: second follow-up.
AB  - Aircrew members are exposed to cosmic radiation and other specific occupational
      factors. In a previous analysis of a large cohort of German aircrew, no increase
      in cancer mortality or dose-related effects was observed. In the present study,
      the follow-up of this cohort of 6,017 cockpit and 20,757 cabin crew members was
      extended by 6 years to 2003. Among male cockpit crew, the resulting all-cancer
      standardized mortality ratio (SMR) (n = 127) is 0.6 (95% CI 0.5-0.8), while for
      brain tumors it is 2.1 (95% CI 1.0-3.9). The cancer risk is significantly raised
      (RR = 2.2, 95% CI 1.2-4.1) among cockpit crew members employed 30 years or more
      compared to those employed less than 10 years. Among both female and male cabin
      crew, the all-cancer SMR and that for most individual cancers are close to 1. The
      SMR for breast cancer among female crew is 1.2 (95% CI 0.8-1.8). Non-Hodgkin's
      Lymphoma among male cabin crew is increased (SMR 4.2; 95% CI 1.3-10.8). However,
      cancers associated with radiation exposure are not raised in the cohort. It is
      concluded that among cockpit crew cancer mortality is low, particularly for lung
      cancer. The positive trend of all cancer with duration of employment persists.
      The increased brain cancer SMR among cockpit crew requires replication in other
      cohorts. For cabin crew, cancer mortality is generally close to population rates.
      Cosmic radiation dose estimates will allow more detailed assessments, as will a
      pooling of updated aircrew studies currently in planning.

PMID- 19841930
TI  - Mathematical modelling of the acid-base chemistry and oxygenation of blood: a
      mass balance, mass action approach including plasma and red blood cells.
AB  - Mathematical models of the acid-base chemistry of blood based upon mass action
      and mass balance equations have become popular as diagnostic tools in intensive
      care. The reference models using this approach are those based on the strong ion
      approach, but these models do not currently take into account the effects of
      oxygen on the buffering characteristics of haemoglobin. As such these models are
      limited in their ability to simulate physiological situations involving
      simultaneous changes of O(2) and CO(2) levels in the blood. This paper describes
      a model of acid-base chemistry of blood based on mass action and mass balance
      equations and including the effects of oxygen. The model is used to simulate the
      mixing of venous blood with the same blood at elevated O(2) and reduced CO(2)
      levels, and the results compared with the mixing of blood sampled from 21 healthy
      subjects. Simulated values of pH, PCO(2), PO(2) and SO(2) in the mixed blood
      compare well with measured values with small bias (i.e. 0.000 pH, -0.06 kPa
      PCO(2), -0.1% SO(2), -0.02 kPa PO(2)), and values of standard deviations (i.e.
      0.006 pH, 0.11 kPa PCO(2), 0.8% SO(2), 0.13 kPa PO(2)) comparable to the
      precision seen in direct measurement of these variables in clinical practice.
      These results indicate that the model can reliably simulate the mixing of blood
      and has potential for application in describing physiological situations
      involving the mixing of blood at different O(2) and CO(2) levels such as occurs
      in the mixing of lung capillary and shunted pulmonary blood.

PMID- 19841931
TI  - Inspiratory muscle training improves 100 and 200 m swimming performance.
AB  - Inspiratory muscle training (IMT) has been shown to improve time trial
      performance in competitive athletes across a range of sports. Surprisingly,
      however, the effect of specific IMT on surface swimming performance remains un
      investigated. Similarly, it is not known whether any ergogenic influence of IMT
      upon swimming performance is confined to specific race distances. To determine
      the influence of IMT upon swimming performance over 3 competitive distances, 16
      competitive club-level swimmers were assigned at random to either an experimental
      (pressure threshold IMT) or sham IMT placebo control group. Participants
      performed a series of physiological and performance tests, before and following 6
      weeks of IMT, including (1) an incremental swim test to the limit of tolerance to
      determine lactate, heart rate and perceived exertion responses; (2) standard
      measures of lung function (forced vital capacity, forced expiratory volume in 1
      s, peak expiratory flow) and maximal inspiratory pressure (MIP); and (3) 100, 200
      and 400 m swim time trials. Training utilised a hand-held pressure threshold
      device and consisted of 30 repetitions, twice per day. Relative to control, the
      IMT group showed the following percentage changes in swim times: 100 m, -1.70%
      (90% confidence limits, +/-1.4%), 200 m, -1.5% (+/-1.0), and 400 m, 0.6% (+/
      1.2). Large effects were observed for MIP and rates of perceived exertion. In
      conclusion, 6 weeks of IMT has a small positive effect on swimming performance in
      club-level trained swimmers in events shorter than 400 m.

PMID- 19841932
TI  - Beta-alanine supplementation reduces acidosis but not oxygen uptake response
      during high-intensity cycling exercise.
AB  - The oral ingestion of beta-alanine, the rate-limiting precursor in carnosine
      synthesis, has been shown to elevate the muscle carnosine content. Carnosine is
      thought to act as a physiologically relevant pH buffer during exercise but direct
      evidence is lacking. Acidosis has been hypothesised to influence oxygen uptake
      kinetics during high-intensity exercise. The present study aimed to investigate
      whether oral beta-alanine supplementation could reduce acidosis during high
      intensity cycling and thereby affect oxygen uptake kinetics. 14 male physical
      education students participated in this placebo-controlled, double-blind study.
      Subjects were supplemented orally for 4 weeks with 4.8 g/day placebo or beta
      alanine. Before and after supplementation, subjects performed a 6-min cycling
      exercise bout at an intensity of 50% of the difference between ventilatory
      threshold (VT) and VO(2peak). Capillary blood samples were taken for
      determination of pH, lactate, bicarbonate and base excess, and pulmonary oxygen
      uptake kinetics were determined with a bi-exponential model fitted to the
      averaged breath-by-breath data of three repetitions. Exercise-induced acidosis
      was significantly reduced following beta-alanine supplementation compared to
      placebo, without affecting blood lactate and bicarbonate concentrations. The time
      delay of the fast component (Td(1)) of the oxygen uptake kinetics was
      significantly reduced following beta-alanine supplementation compared to placebo,
      although this did not reduce oxygen deficit. The parameters of the slow component
      did not differ between groups. These results indicate that chronic beta-alanine
      supplementation, which presumably increased muscle carnosine content, can
      attenuate the fall in blood pH during high-intensity exercise. This may
      contribute to the ergogenic effect of the supplement found in some exercise
      modes.

PMID- 19841933
TI  - Accumulation of 2H2O in plasma and eccrine sweat during exercise-heat stress.
AB  - The purpose of this research was to characterize the movement of ingested water
      through body fluids, during exercise-heat stress. Deuterium oxide ((2)H(2)O)
      accumulation in plasma and eccrine sweat was measured at two sites (back and
      forehead). The exercise of 14 males was controlled via cycle ergometry in a warm
      environment (60 min; 28.7 degrees C, 51%rh). Subjects consumed (2)H(2)O (0.15 mg
      kg(-1), 99.9% purity) mixed in flavored, non-caloric, colored water before
      exercise, then consumed 3.0 ml kg(-1) containing no (2)H(2)O every 15 min during
      exercise. We hypothesized that water transit from mouth to skin would occur
      before 15 min. (2)H(2)O appeared rapidly in both plasma and sweat (P < 0.05),
      within 10 min of water consumption. The ratio (2)H(2)O/H(2)O (D:H) was 47.3-55.0
      times greater in plasma than in back sweat at minutes 10, 20, and 30 (DeltaD:H
      relative to baseline). At elapsed minute 20, the mean rate of deuterium
      accumulation (DeltaD:H min(-1)) in plasma was 14.9 and 23.7 times greater than in
      forehead and back sweat samples, respectively. Mean (+/-SE) whole-body sweat rate
      was 1.04 +/- 0.05 L h(-1) and subjects with the greatest whole-body sweat rate
      exhibited the greatest peak deuterium enrichment in sweat (r(2) = 0.87,
      exponential function); the peak (2)H(2)O enrichment in sweat was not proportional
      (P > 0.05) to body mass, volume of the deuterium dose, or total volume of fluid
      consumed. These findings clarify the time course of fluid movement from mouth to
      eccrine sweat glands, and demonstrate considerable differences of (2)H(2)O
      enrichment in plasma versus sweat.

PMID- 19841934
TI  - Understanding effects on excitability of simulated I (h) modulation in simple
      neuronal models.
AB  - The hyperpolarization-activated, inward, mixed cation current, I (h), appears in
      a wide variety of cells in the nervous system, contributes to diverse neuronal
      properties, and is up-regulated by a number of important neurotransmitters. Up
      regulation of I (h) is usually associated with an excitability-enhancing
      depolarization of resting membrane potential and an excitability-depressing
      shunting effect caused by a decrease in input resistance. In order to gain a
      better understanding of the interaction of these effects and their influence on
      excitability with I (h) modulation, we systematically analyze changes in neuronal
      properties associated with excitability during I (h) modulation in simplified,
      yet, biophysical neuron models based on a hippocampal pyramidal neuron. We
      simulate I (h) modulation by varying both its maximal conductance and its half
      activation voltage, mimicking the effects of cAMP-linked neurotransmitters,
      through ranges of physiologically realistic parameter regimes. Of particular
      interest is the contribution of the different effects of I (h) up-regulation when
      membrane potentials are held at common levels and neuronal excitability is
      probed. Our modeling results suggest that, although holding potentials at common
      levels may compensate for changes in resting membrane potentials, this protocol
      may exaggerate the excitability-depressing influences of changes in input
      resistances with I (h) up-regulation.

PMID- 19841935
TI  - Compensatory regulation of the sodium/phosphate cotransporters NaPi-IIc (SCL34A3)
      and Pit-2 (SLC20A2) during Pi deprivation and acidosis.
AB  - The role of four Pi transporters in the renal handling of Pi was analyzed using
      functional and molecular methods. The abundance of NaPi-IIa, NaPi-IIc, and Pit-2
      was increased by 100% in kidney from rats on a 0.1% Pi diet, compared to a 0.6%
      Pi diet. Pit-1 was not modified. Type II-mediated Pi uptake in Xenopus oocytes
      increased as the pH of the uptake medium increased, and the opposite occurred
      with Pit-1 and Pit-2. At pH 6.0, Pi uptake mediated through type II was
      approximately 10% of the uptake at pH 7.5, but the uptake through Pit-2 was 250%
      of the activity at pH 7.5. Real brush-border membrane vesicles (BBMV) responded
      to pH changes following the same pattern as type II transporters. Adaptation to a
      0.1% Pi diet was accompanied by a 65% increase in the V (max) of BBMV Pi
      transport at pH 7.5, compared to a 0.6% Pi diet. The increase was only 11% at pH
      6.0. Metabolic acidosis increased the expression of NaPi-IIc and Pit-2 in animals
      adapted to a low Pi diet, and phosphaturia was only observed in control diet
      animals. The combination of the pH effect, Pi adaptation, and metabolic acidosis
      suggests very modest involvement of Pit-2 in renal Pi handling. Real-time PCR and
      mathematical analyses of transport findings suggest that NaPi-IIa RNA accounts
      for 95% of all Pi transporters and that type II handles 97% of Pi transport at pH
      7.5 and 60% of Pi transport at pH 6.0, depending on the pH and the physiological
      conditions.

PMID- 19841937
TI  - Full analysis of the prostatic urethra at the time of radical cystoprostatectomy
      for bladder cancer: impact on final disease stage.
AB  - Prostate involvement is a major prognostic element in urothelium carcinoma
      staging after radical cystoprostatectomy (RCP) for muscle invasive bladder
      cancer. While appropriate pTNM stage is necessary for adequate treatment, no
      standard procedure exists up to now for macroscopic sampling of the prostate in
      RCP in daily practice. We therefore propose a protocol where examination of the
      whole prostatic urethra (PU) is possible, without using whole mount sections.
      From 2008 to June 2009, RCP were sampled according to a macroscopic protocol
      permitting the whole length and the underlying stroma of PU to be visualized.
      Data were compared with our series or RCP from 2000-2007, when the PU was
      evaluated with a more simple protocol. One hundred and one specimens were
      examined between 2000-2007, 25 until June 2009. In the latter series, we found
      pT4 bladder cancer in 36% versus 21%, Cis in the PU in 28% versus 14%, and
      additional prostate cancer was seen in 44% compared with 13% (p = 0.0004) in the
      2008-2009 group versus the 2000-2007 group, respectively. Our proposed protocol
      better detects prostate involvement by bladder cancer, therefore providing a
      better final stage of the patients. We propose a macroscopic protocol where the
      whole PU and the underlying stroma can be examined without the use of whole mount
      sections. Data are similar to those published in the recent literature, where
      whole mount sections were used. This protocol also permits better detection of
      concomitant prostate carcinomas.

PMID- 19841938
TI  - Histological heterogeneity of Ewing's sarcoma/PNET: an immunohistochemical
      analysis of 415 genetically confirmed cases with clinical support.
AB  - Ewing's sarcoma (ES)/peripheral neuroectodermal tumor (PNET) are malignant
      neoplasms affecting children and young adults. We performed a study to typify the
      histological diversity and evaluate antibodies that may offer
      diagnostic/prognostic support. In total, 415 cases of genetically confirmed
      paraffin-embedded ES/PNET were analyzed on whole sections and in tissue
      microarrays. This study confirms the structural heterogeneity of ES/PNET,
      distinguishing three major subtypes: conventional ES (280 cases); PNET (53
      cases); and atypical ES/PNET (80), including large cells, vascular-like patterns,
      spindle pattern, and adamantinoma-like configuration. All cases presented
      positivity for at least three of the four tested antibodies (CD99, FLI1, HNK1,
      and CAV1). CAV1 appeared as a diagnostic immunomarker of ES/PNET being positive
      in CD99-negative cases. Hence, the immunohistochemical analysis confirmed the
      diagnostic value of all four antibodies, which together cover more than 99% of
      the tumors, independently of the histological variety. The univariate analysis
      for survival revealed atypical ES as the only histological parameter apparently
      associated with less favorable clinical outcome, particularly in the subgroup of
      patients treated with surgery. In conclusion, the diagnosis of atypical ES is a
      challenge for the pathologist and needs support from molecular techniques to
      perform an optimal differential diagnosis with other small round cell tumors.

PMID- 19841939
TI  - Diagnosis, treatment and follow-up of 25 patients with melamine-induced kidney
      stones complicated by acute obstructive renal failure in Beijing Children's
      Hospital.
AB  - A total of 25 Chinese patients aged 6 to 36 months hospitalised at Beijing
      Children's Hospital due to melamine-induced kidney stones complicated by acute
      obstructive renal failure in 2008 were included in a study in order to diagnose
      and treat these special cases more effectively. Feeding history, clinical
      presentation, ultrasound findings, treatments and effects were summarised. Twelve
      to seventeen months follow-up was reported also. Ultrasound examination showed
      that calculi were located at the kidney and ureters. Stones were composed of both
      uric acid and melamine in a molar ratio of 1.2:1 to 2.1:1. Treatments providing
      liquid plus alkalisation of urine proved to be effective in helping the patients
      pass the stones. Surgical intervention was needed in severe cases. Renal function
      returned to normal in all 25 patients after various durations of therapy. Sixty
      eight percent of the patients expelled all of the calculi within 3 months, 90% in
      6 months and 95% in 9 months, without sequelae till now. Melamine-contaminated
      milk formula can cause kidney stones in infants, which should be diagnosed by
      feeding history, clinical symptoms and ultrasound examination. Composition of the
      stones was not only of melamine but also uric acid. Providing liquid orally or
      intravenously plus alkalisation of urine proved to promote the removal of the
      stones. Follow-up of 12 to 17 months after discharge showed no sequelae.

PMID- 19841940
TI  - Clinical practice: neonatal resuscitation. A Dutch consensus.
AB  - The updated Dutch guidelines on Neonatal Resuscitation assimilate the latest
      evidence in neonatal resuscitation. Important changes with regard to the 2004
      guidelines and controversial issues concerning neonatal resuscitation are
      reviewed, and recommendations for daily practice are provided and argued in the
      context of the ILCOR 2005 consensus.

PMID- 19841941
TI  - Ethical principles and recommendations for the medical management of differences
      of sex development (DSD)/intersex in children and adolescents.
AB  - The medical management of differences of sex development (DSD)/intersex in early
      childhood has been criticized by patients' advocates as well as bioethicists from
      an ethical point of view. Some call for a moratorium of any feminizing or
      masculinizing operations before the age of consent except for medical
      emergencies. No exhaustive ethical guidelines have been published until now. In
      particular, the role of the parents as legal representatives of the child is
      controversial. In the article, we develop, discuss, and present ethical
      principles and recommendations for the medical management of intersex/DSD in
      children and adolescents. We specify three basic ethical principles that have to
      be respected and substantiate them. The article includes a critical discussion of
      the best interest of the child and of family privacy. The argumentation draws
      upon recommendations by the working group "Bioethics and Intersex" within the
      German Network DSD/Intersex, which are presented in detail. Unlike other
      recommendations with regard to intersex, these guidelines represent a
      comprehensive view of the perspectives of clinicians, patients, and their
      families. CONCLUSION: The working group identified three leading ethical
      principles that apply to DSD management: (1) to foster the well-being of the
      child and the future adult, (2) to uphold the rights of children and adolescents
      to participate in and/or self-determine decisions that affect them now or later,
      and (3) to respect the family and parent-child relationships. Nine
      recommendations for the management of DSD indicate how these ethical principles
      can spelled out and balanced against each other in the clinical setting.

PMID- 19841942
TI  - Muscular sarcocystosis in wild carnivores in Honshu, Japan.
AB  - A total of 65 free-living carnivores collected on Honshu Island, Japan were
      examined for muscular Sarcocystis species infections. Among them, 12 Japanese
      raccoon dogs (Nyctereutes procyonoides viverrinus), one Japanese red fox (Vulpes
      vulpes japonica), three Japanese martens (Martes melampus melampus), and two
      Japanese badgers (Meles meles anakuma) were found to have sarcocysts in their
      muscles. No inflammatory reactions associated with sarcocysts were observed.
      Ultrastructurally, the sarcocysts detected in the Japanese raccoon dogs, Japanese
      red fox, and Japanese martens were similar to each other, with the sarcocyst wall
      being thin and exhibiting minute undulations. On the other hand, the sarcocysts
      detected in the Japanese badgers had a thick cyst wall with numerous finger-like
      protrusions which contained microtubules. The species of Sarcocystis in Japanese
      carnivores remain to be determined. This is the first published report on
      muscular sarcocystosis in Japanese carnivores.

PMID- 19841943
TI  - High prevalence of helminth parasites in feral cats in Majorca Island (Spain).
AB  - Feral cats are widespread in the countryside of Majorca (Balearic Islands,
      Spain). Since they are not subject of sanitary control, they can act as reservoir
      of parasites of veterinary and zoonotic interest. The main organs of 58 wild
      trapped cats in 16 different areas from Majorca were analyzed by helminths. All
      the cats were parasitized, and eight species of helminths were retrieved (mean =
      3.4 species per cat, with 74% of the cats harboring three or more species). Seven
      of them presented a prevalence >20%: Joyeuxiella pasqualei (76%), Diplopylidium
      acanthotetra (60%), Dipylidium carracidoi (33%), Taenia taeniaeformis (22%),
      Ancylostoma tubaeforme (91%), and Toxocara cati (35%) in the gastrointestinal
      tract, and Oslerus rostratus (24%) in lungs. The A. tubaeforme prevalence and
      intensity (mean = 30, up to 396) is the highest recorded for a population of
      cats. Prevalence and abundance of J. pasqualei and D. acanthotetra were strongly
      associated, secondary to the use of the same intermediary host (geckos). Other
      positive associations found are probably related to host susceptibility.
      Abundance of D. acanthotetra, T. cati, and A. tubaeforme and the number of
      species per host were negatively correlated with cat body condition (assessed by
      the kidney fat index). Females were more frequently parasitized by A. tubaeforme
      than males, and adult females were more heavily infested by J. pasqualei and D.
      acanthotetra than cats from other groups. These and other findings are discussed
      in relation with host ecology. Feral cats serve as reservoirs of helminths in the
      countryside of Majorca and their populations should be controlled.

PMID- 19841944
TI  - Adam12 plays a role during uterine decidualization in mice.
AB  - In mouse, decidualization is characterized by the proliferation of stromal cells
      and their differentiation into specialized type of cells (decidual cells) with
      polyploidy, surrounding the implanting blastocyst. However, the mechanisms
      involved in these processes remain poorly understood. Using multiple approaches,
      we have examined the role of Adam12 in decidualization during early pregnancy in
      mice. Adam12 is spatiotemporally expressed in decidualizing stromal cells in
      intact pregnant females and in pseudopregnant mice undergoing artificially
      induced decidualization. In the ovariectomized mouse uterus, the expression of
      Adam12 is upregulated after progesterone treatment, which is primarily mediated
      by nuclear progesterone receptor. In a stromal cell culture model, the expression
      of Adam12 gradually rises with the progression of stromal decidualization,
      whereas the attenuated expression of Adam12 after siRNA knockdown significantly
      blocks the progression of decidualization. Our study suggests that Adam12 is
      involved in promoting uterine decidualization during pregnancy.

PMID- 19841945
TI  - Your worst enemy could be your best friend: predator contributions to invasion
      resistance and persistence of natives.
AB  - Native predators are postulated to have an important role in biotic resistance of
      communities to invasion and community resilience. Effects of predators can be
      complex, and mechanisms by which predators affect invasion success and impact are
      understood for only a few well-studied communities. We tested experimentally
      whether a native predator limits an invasive species' success and impact on a
      native competitor for a community of aquatic insect larvae in water-filled
      containers. The native mosquito Aedes triseriatus alone had no significant effect
      on abundance of the invasive mosquito Aedes albopictus. The native predatory
      midge Corethrella appendiculata, at low or high density, significantly reduced A.
      albopictus abundance. This effect was not caused by trait-mediated oviposition
      avoidance of containers with predators, but instead was a density-mediated effect
      caused by predator-induced mortality. The presence of this predator significantly
      reduced survivorship of the native species, but high predator density also
      significantly increased development rate of the native species when the invader
      was present, consistent with predator-mediated release from interspecific
      competition with the invader. Thus, a native predator can indirectly benefit its
      native prey when a superior competitor invades. This shows the importance of
      native predators as a component of biodiversity for both biotic resistance to
      invasion and resilience of a community perturbed by successful invasion.

PMID- 19841946
TI  - Locomotor performance in an invasive species: cane toads from the invasion front
      have greater endurance, but not speed, compared to conspecifics from a long
      colonised area.
AB  - Cane toads (Bufo marinus) are now moving about 5 times faster through tropical
      Australia than they did a half-century ago, during the early phases of toad
      invasion. Radio-tracking has revealed higher daily rates of displacement by toads
      at the invasion front compared to those from long-colonised areas: toads from
      frontal populations follow straighter paths, move more often, and move further
      per displacement than do toads from older (long-established) populations. Are
      these higher movement rates of invasion-front toads associated with modified
      locomotor performance (e.g. speed, endurance)? In an outdoor raceway, toads
      collected from the invasion front had similar speeds, but threefold greater
      endurance, compared to conspecifics collected from a long-established population.
      Thus, increased daily displacement in invasion-front toads does not appear to be
      driven by changes in locomotor speed. Instead, increased dispersal is associated
      with higher endurance, suggesting that invasion-front toads tend to spend more
      time moving than do their less dispersive conspecifics. Whether this increased
      endurance is a cause or consequence of behavioural shifts associated with rapid
      dispersal is unclear. Nonetheless, shifts in endurance between frontal and core
      populations of this invasive species point to the complex panoply of traits
      affected by selection for increased dispersal ability on expanding population
      fronts.

PMID- 19841947
TI  - Captopril-enhanced renal scintigraphy in the diagnosis of pediatric hypertension.
AB  - Hypertension in childhood is no longer a rare condition mainly secondary to
      renal, or renovascular diseases, as a growing proportion of children are obese
      and hypertensive, with the phenotype of metabolic syndrome. Thus, we need to
      reconsider our practice in the examination of the hypertensive child and redefine
      the place of non-invasive methods for screening of renovascular hypertension, and
      specifically, to evaluate the value of captopril-enhanced renal scintigraphy at
      the two ends of the palette: the obese child with hypertension and the severely
      hypertensive prepubertal child. Renal artery stenosis in children is mainly due
      to fibromuscular dysplasia and stenoses associated with syndromes involving
      single or multiple smaller branch vessels. This explains the low specificity and
      sensitivity of the color-Doppler ultrasound method and captopril renal
      scintigraphy. Even the more sophisticated computed tomography (CT) and magnetic
      resonance imaging (MRI) angiographic techniques are, at present, not sensitive
      enough to exclude stenoses of the small branches definitely. Thus, children in
      whom there is a strong suggestion of renovascular hypertension should undergo
      angiography with a view to endovascular treatment, as non-invasive imaging has no
      significant benefit and might lead to a delay in treatment. In the cases when the
      probability of renovascular disease is moderate a basic assessment of renal
      function and structure is sufficient. In the neonate, catheter-associated
      thromboembolic disease is among the most common causes hypertension. It should be
      controlled medically until the patient is old enough to undergo angiography and
      angioplasty successfully. Thus, in this age group, there is a place for
      functional imaging with renal sonography and angiotensin-converting enzyme
      inhibitor (ACEI) renography to detect hemodynamically significant renovascular
      disease, with the limitations mentioned above. However, the rapid technical
      evolution of non-invasive methods requires periodic re-consideration of the
      actual standpoints.

PMID- 19841948
TI  - Urinary macrophage migration inhibitory factor in children with urinary tract
      infection.
AB  - Macrophage migration inhibitory factor (MIF) plays an essential
      pathophysiological role in inflammatory reactions. The aim of this study was to
      investigate the clinical utility of urine MIF (uMIF) level in predicting urinary
      tract infections (UTI). This multicenter, prospective study was conducted over a
      1-year period between March 2008 and March 2009. Sixty patients with symptomatic
      culture-proven UTI and 29 healthy children were recruited. Urine MIF was measured
      by enzyme-linked immunosorbent assay. The mean MIF level was found to be
      significantly higher in the UTI group than in the control group (1082.82 vs.
      211.45 pg/ml, p = 0.0001). Receiver operating characteristic (ROC) analysis
      revealed that the optimal cut-off uMIF level was 295 pg/ml for uMIF to predict
      UTI. The sensitivity and specificity of this cut-off level were 91.7% and 69%,
      respectively. Mean uMIF/creatinine (Cr) was also significantly higher in the UTI
      group than in the control group (2400.69 vs. 267.56 pg/mgCr, p = 0.0001). At a
      cut-off of 815 pg/mgCr for uMIF/Cr, the sensitivity and specificity were 95 and
      79%, respectively. The area under curve (AUC) was 0.848 (standard error 0.040,
      95% confidence interval 0.756-0.915) for uMIF and 0.889 (0.034, 0.805-0.946) for
      uMIF/Cr. Urine MIF/Cr was significantly higher in the patients with a positive
      leukocyte esterase reaction in the urine (p = 0.047), leukocytosis (p = 0.0001)
      and positive C-reactive protein level in serum (p = 0.003). The uMIF level was
      not related to leukocytosis, positive CRP level in serum and leukocyte esterase
      reaction in the urine. Neither uMIF nor uMIF/Cr were correlated to the positive
      urine nitrite test, pyuria, urine pH and specific gravity (p > 0.05). These
      results suggest that urine MIF and uMIF/Cr can be used for the early prediction
      of UTI in children.

PMID- 19841949
TI  - Unmet supportive needs of cancer patients in an acute care hospital in Japan--a
      census study.
AB  - PURPOSE: Little research has been done on supportive needs of cancer patients in
      acute hospitals in Japan. This study aims to comprehensively assess the unmet
      supportive needs of hospitalized cancer patients, as well as literacy and
      utilization of appropriate professional care. METHODS: All cancer patients (aged
      20 to 80 years) who were hospitalized in a university hospital in Tokyo during
      the designated 3-day period between September 1 and October 31, 2007 were
      recruited for participation in the study. The M.D. Anderson Symptom Inventory,
      Brief Cancer-Related Worry Inventory, and Hospital Anxiety and Depression Scale
      were administered. Patients' knowledge and use of relevant services were
      evaluated. The results were compared with those of non-cancer patients in the
      same treatment settings. RESULTS: A total of 125 cancer patients and 59 non
      cancer patients were enrolled. Cancer patients and non-cancer patients equally
      suffered from physical symptoms (15-26% had severe appetite loss, 18-19% had
      severe dry mouth, and 16-22% had severe pain); however, psychological distress of
      cancer patients exceeded that of non-cancer patients (28.0% vs 8.5%; p <= 0.05).
      Severe psychological distress was associated with severe worry about future
      prospects or interpersonal and social issues and presence of two or more severe
      symptoms. Two thirds of the patients with severe psychological distress knew
      about the psychiatric division, but only one third actually sought treatment.
      CONCLUSIONS: Needs related to psychological issues were more prevalent among
      cancer patients than among non-cancer patients, despite a similar level of
      physical distress. Special attention should be paid to cancer patients who worry
      over future prospects or interpersonal and social issues, and those who have two
      or more severe symptoms.

PMID- 19841950
TI  - Bloodless cancer treatment results of patients who do not want blood transfusion:
      single center experience of 77 cases.
AB  - PURPOSE: Certain patients may be unwilling to accept blood products for religious
      reasons. In this study, we have assessed the clinical cancer treatment outcomes
      of Jehovah's Witnesses (JW) cancer patients in order to identify the risks
      associated with their treatment, as well as their transfusion needs. METHODS: We
      analyzed 77 cases of histologically confirmed cancer patients (JW) from January
      2001 to April 2008. RESULTS: The median age of the patients was 59 years (range,
      8-83 years). The most common primary site was the stomach (20.8%), followed by
      the breast (14.3%), and colorectal region (11.7%). Operations were performed on
      44 patients (89.8%). Changes in complete blood count profiles after operation
      were detected in the patients' hemoglobin (mean +/- SD; 12.7 +/- 2.1 g/dL to 10.6
      +/- 2.3 g/dL, P < 0.001). Twenty-six patients received adjuvant chemotherapy.
      Among these, 21 (80.8%) completed their planned schedule. One hundred twenty
      seven cycles of palliative intravenous chemotherapy were administered to 19
      patients. Granulocyte-colony stimulating factor and erythropoietin were used in
      45 and 20 cycles of treatment, respectively. Grade > or =III thrombocytopenia and
      anemia were noted in 3.9% and 2.4% of the patients. Three- and 5-year survival
      rates were 80% and 70%, respectively. The most frequent cause of death was
      disease progression rather than bleeding. CONCLUSIONS: Bloodless cancer operation
      and chemotherapy were not accompanied by serious complications. A few cases of
      palliative chemotherapy also required transfusions. A prospective cohort study
      group will need to be used to determine precisely the safety of bloodless cancer
      treatment and the efficacy of transfusion alternatives.

PMID- 19841951
TI  - Docking and 3D-QSAR studies of acetohydroxy acid synthase inhibitor sulfonylurea
      derivatives.
AB  - Docking and three dimensional quantitative-structure activity relationship (3D
      QSAR) studies were performed on acetohydroxy acid synthase (AHAS) inhibitor
      sulfonylurea analogues with potential herbicidal activity. The 3D-QSAR studies
      were carried out using shape, spatial and electronic descriptors along with a few
      structural parameters. Genetic function approximation (GFA) was used as the
      chemometric tool for this analysis. The whole data set (n = 45) was divided into
      a training set (75% of the data set) and a test set (remaining 25%) on the basis
      of the K-means clustering technique on a standardised topological,
      physicochemical and structural descriptor matrix. Models developed from the
      training set were used to predict the activity of the test set compounds. All
      models were validated internally, externally and using the Y-randomisation
      technique. Docking studies suggested that the molecules bind within a pocket of
      the enzyme formed by some important amino acid residues (Met351, Asp375, Arg377,
      Gly509, Met570 and Val571). In QSAR studies, molecular shape analysis showed that
      bulky substitution at the R(1) position may enhance AHAS inhibitory activity.
      Charged surface area descriptors suggested that negative charge distributed over
      a large surface area may enhance this activity. The hydrogen bond acceptor
      parameter supported the charged surface area descriptors and suggested that, for
      better activity, the number of electronegative atoms present in the molecule
      should be high. The spatial descriptors show that, for better activity, the
      molecules should possess a bulky substituent and a small substitution at the R(2)
      and R(3) positions, respectively.

PMID- 19841952
TI  - Effect of oral contrast for abdominal computed tomography on emergency department
      length of stay.
AB  - Computed tomography of the abdomen and/or pelvis (CTAP) is frequently used in the
      emergency department (ED) allowing diagnosis of a variety of conditions, but
      requiring a prolonged period of preparation. To determine whether not requiring
      oral contrast for CTAP reduces ED length of stay (LOS). Retrospective cohort of
      adult patients visiting an academic ED over 13 weeks around a radiology protocol
      change. Before the change, many CTAPs required oral contrast; thereafter, oral
      contrast was not required. LOS was compared before and after the change among all
      adult ED patients. Among patients undergoing CTAP, adjusted LOS and time to CTAP
      were compared using multivariate linear regression. 20,464 adult ED visits
      occurred over the study period, including 1,806 where a CTAP was performed. Oral
      contrast usage decreased from 42.5% of CTAP to 12.2% (difference 30.3%, 95%
      confidence interval 38.7% to 46.3%). There was no change in LOS among all ED
      visits. Among ED visits where a CTAP was performed, median time to CTAP decreased
      by 27 min and median LOS decreased by 30 min. Adjusted LOS decreased from 324 min
      (312-337) to 297 min (285-309). Not routinely requiring oral contrast for CTAP in
      the ED is associated with a half-hour reduction in LOS among all patients
      undergoing CTAP.

PMID- 19841953
TI  - Genes influencing spinal bone mineral density in inbred F344, LEW, COP, and DA
      rats.
AB  - Previously, we identified the regions of chromosomes 10q12-q31 and 15p16-q21
      harbor quantitative trait loci (QTLs) for lumbar volumetric bone mineral density
      (vBMD) in female F2 rats derived from Fischer 344 (F344) x Lewis (LEW) and
      Copenhagen 2331 (COP) x Dark Agouti (DA) crosses. The purpose of this study is to
      identify the candidate genes within these QTL regions contributing to the
      variation in lumbar vBMD. RNA was extracted from bone tissue of F344, LEW, COP,
      and DA rats. Microarray analysis was performed using Affymetrix Rat Genome 230
      2.0 Arrays. Genes differentially expressed among the rat strains were then ranked
      based on the strength of the correlation with lumbar vBMD in F2 animals derived
      from these rats. Quantitative PCR (qPCR) analysis was performed to confirm the
      prioritized candidate genes. A total of 285 genes were differentially expressed
      among all strains of rats with a false discovery rate less than 10%. Among these
      genes, 18 candidate genes were prioritized based on their strong correlation (r
      (2) > 0.90) with lumbar vBMD. Of these, 14 genes (Akap1, Asgr2, Esd, Fam101b,
      Irf1, Lcp1, Ltc4s, Mdp-1, Pdhb, Plxdc1, Rabep1, Rhot1, Slc2a4, Xpo4) were
      confirmed by qPCR. We identified several novel candidate genes influencing spinal
      vBMD in rats.

PMID- 19841955
TI  - Behavior of an electrolytic cell containing two groups of ions submitted to a
      step-like external voltage.
AB  - The transient and equilibrium behaviors of an electrolytic cell containing two
      groups of ions submitted to an external voltage is considered. The analysis is
      performed analytically and numerically, considering the electrolytic solution as
      a dispersion of ions in an insulating liquid. According to our results, the
      dynamic of the system corresponds to a multirelaxation problem and the relaxation
      time related to a new type of free diffusion is able to capture the essential
      characteristics of the evolution of the variables of the system. We also show
      that, contrary to what expected, the relaxation time related to the ambipolar
      diffusion is not a solution of the eigenvalues equation.

PMID- 19841954
TI  - Abscisic acid stimulated ripening and gene expression in berry skins of the
      Cabernet Sauvignon grape.
AB  - We investigated the effect of exogenous abscisic acid (ABA) application on the
      transcriptome as well as the phenolic profiles in the skins of Vitis vinifera cv.
      Cabernet Sauvignon grape berries grown on the vine and cultured in vitro. ABA
      application rapidly induced the accumulation of anthocyanin and flavonol.
      Correlatively, the structural genes in the phenylpropanoid and flavonoid
      pathways, their transcriptional regulators, as well as genes considered to be
      involved in the acylation and transport of anthocyanin into the vacuole, were
      upregulated by ABA treatment. The Genechip analysis showed that the ABA treatment
      significantly up- or downregulated a total of 345 and 1,482 transcripts in the
      skins of berries grown on the vine and cultured in vitro, respectively. Exogenous
      ABA modulated the transcripts associated with osmotic responses, stress
      responses, cell wall modification, auxin and ethylene metabolism and responses,
      in addition to the induction of anthocyanin biosynthetic genes, and reduced those
      associated with photosynthesis; approximately half of these transcripts were
      identical to the previously reported ripening-specific genes.

PMID- 19841956
TI  - Degradation of phenols in olive oil mill wastewater by biological, enzymatic, and
      photo-Fenton oxidation.
AB  - BACKGROUND, AIM, AND SCOPE: Olive oil mill wastewater (OOMW) environmental
      impacts minimization have been attempted by developing more effective processes,
      but no chemical or biological treatments were found to be totally effective to
      mitigate their impact on receiving systems. This work is the first that reports
      simultaneously the efficiency of three different approaches: biological treatment
      by two fungal species (Trametes versicolor or Pleurotus sajor caju), enzymatic
      treatment by laccase, and chemical treatment by photo-Fenton oxidation on phenols
      removal. MATERIALS AND METHODS: Those treatments were performed on OOMW with or
      without phenol supplement (p-coumaric, vanillin, guaiacol, vanillic acid, or
      tyrosol). OOMW samples resulted from treatments were extracted for phenols using
      liquid-liquid extraction and analyzed by gas chromatography coupled to mass
      spectrometry. RESULTS: Treatment with T. versicolor or P. sajor caju were able to
      remove between 22% and 74% and between 8% and 76% of phenols, respectively.
      Treatment by laccase was able to reduce 4% to 70% of phenols whereas treatment by
      photo-Fenton oxidation was responsible for 100% phenols reduction. DISCUSSION:
      Range of phenol degradation was equivalent between T. versicolor, P. sajor caju
      and laccase for p-coumaric, guaiacol, caffeic acid, and tyrosol in supplemented
      OOMW, which enhances this enzyme role in the biological treatment promoted by
      these two species. CONCLUSIONS: Phenols were removed more efficiently by photo
      Fenton treatment than by biological or enzymatic treatments. RECOMMENDATIONS AND
      PERSPECTIVES: Use of fungi, laccase, or photo-Fenton presents great potential for
      removing phenols from OOMW. This should be further assessed by increasing the
      application scale and the reactor configurations effect on the performance,
      besides a toxicity evaluation of treated wastewater in comparison to raw
      wastewater.

PMID- 19841957
TI  - Re: "Talonavicular joint arthrodesis for the treatment of pes planus valgus in
      older children and adolescents with cerebral palsy".

PMID- 19841958
TI  - From molecules to the biosphere: Nikolai V. Timofeeff-Ressovsky's (1900-1981)
      research program within a totalitarian landscape.
AB  - Nikolai Vladimirovich Timofeeff-Ressovsky was one of the key figures in the
      Synthetic Theory of Evolution. Living and researching under what was arguably the
      two most powerful and cruel totalitarian regimes in human history, the Third
      Reich and the Soviet Union, Timofeeff-Ressovsky succeeded in developing an
      ambitious research program aiming to explain evolution on all major levels, from
      the molecular-genetic, the populational, and the biogeocenotic to the level of
      the entire Biosphere. Yet his scientific biography remains largely unwritten and
      his role under totalitarianism, especially in Nazi Germany, remains highly
      controversial. Here we approach the problem of his hypothetical cooperation with
      Nazi authorities examining both the crucial episodes of his biography and
      summarizing the development of his research program. We conclude that the key
      decisions he made reflected the specificity of his research program that was
      focused on the fundamental questions of evolutionary biology.

PMID- 19841959
TI  - APOB-516 T allele homozygous subjects are unresponsive to dietary changes in a
      three-month primary intervention study targeted to reduce fat intake.
AB  - Dietary guidelines aim to control fat intake and reduce cardiovascular risk but
      an important interindividual variability occurs among subjects. The objective was
      to investigate whether the response of lipid and glucose homeostasis parameters
      after a three-month diet aimed at reducing cardiovascular risk could be modulated
      by the -516C/T polymorphism in the apolipoprotein B gene (APOB). Middle-aged men
      (n = 69) and women (n = 100) with moderate cardiovascular disease risk were
      advised to reduce total energy and fat intakes and replace saturated dietary fat
      by monounsaturated and polyunsaturated fat. Subjects were genotyped for APOB
      516C/T polymorphism. At the entry and at the end of the three-month period,
      fasting and postprandial plasma lipid analyses were performed. At entry, subjects
      homozygous for the APOB-516 T allele exhibited significantly lower fasting plasma
      concentrations of apolipoprotein B 48, triglycerides and triglyceride-rich
      lipoproteins-triglycerides compared to C carrier subjects. After the diet period,
      while C carrier subjects presented a clear improvement of most biological
      parameters, paradoxically T/T subjects did not modify them. In addition, the apoB
      48 postprandial response after a standardized mixed test meal was not improved in
      T/T subjects after the three-month diet, contrary to C allele carriers. Even
      though their phenotype at entry does not show any significant increase of risk
      factors when compared to other groups, subjects homozygous for the APOB-516 T
      allele are unresponsive to a healthy diet that improves cardiovascular risk
      status in the whole population.

PMID- 19841961
TI  - Effect of alteration zones on water quality: a case study from Biga Peninsula,
      Turkey.
AB  - Widespread and intense zones of silicified, propylitic, and argillic alteration
      can be found in the Can volcanics of Biga Peninsula, northwest Turkey. Most of
      the springs in the study area surface out from the boundary between fractured
      aquifer (silicified zone) and impervious boundary (argillic zone). This study
      focuses on two such springs in Kirazli area (Kirazli and Balaban springs) with a
      distinct quality pattern. Accordingly, field parameters (temperature, pH, and
      electrical conductivity), major anion and cation (sodium, potassium, calcium,
      magnesium, chloride, bicarbonate, and sulfate), heavy metals (aluminum, arsenic,
      barium, chromium, cobalt, cupper, iron, lithium, manganese, nickel, lead, and
      zinc), and isotopes (oxygen-18, deuterium, and tritium) were determined in water
      samples taken from these springs during 2005 through 2007. The chemical analyses
      showed that aluminum concentrations were found to be two orders of magnitude
      greater in Kirazli waters (mean value 13813.25 microg/L). The levels of this
      element exceeded the maximum allowable limits given in national and international
      standards for drinking-water quality. In addition, Balaban and Kirazli springs
      are >55 years old according to their tritium levels; Kirazli spring is older than
      Balaban spring. Kirazli spring is also more enriched than Balaban spring based in
      oxygen-18 and deuterium values. Furthermore, Kirazli spring water has been in
      contact with altered rocks longer than Balaban spring water, according to its
      relatively high chloride and electrical conductivity values.

PMID- 19841960
TI  - Improving the oral bioavailability of beneficial polyphenols through designed
      synergies.
AB  - A substantial and growing consumer demand exists for plant-based functional foods
      that improve general health and wellbeing. Amongst consumed phytochemicals, the
      polyphenolic compounds tend to be the most bioactive. Many commonly consumed
      polyphenols have been shown to have specific and potent health-promoting
      activities when assessed by high-throughput in vitro assays and when administered
      to experimental animals by injection. However, very few have been shown to have
      any beneficial effects in animals or man when orally consumed, because of the
      poor bioavailability exhibited by most polyphenols following the ingestion.
      Consumed polyphenols, like most pharmaceuticals, are regarded as xenobiotics by
      the body and must overcome many barriers, including extensive enzymatic and
      chemical modification during digestion and absorption, to reach their site(s) of
      action. This is especially true for polyphenols targeting the brain, which is
      protected by the tightly regulated blood-brain barrier. Interestingly, many
      polyphenols are also known to specifically modify some of the metabolic and
      transport processes that govern bioavailability. Therefore, the opportunity
      exists to increase the bioactivity of beneficial polyphenols by designing
      specific synergistic interactions with polyphenols that improve their oral
      bioavailability. This hypothesis and review paper will discuss some of the
      endogenous systems that limit the bioavailability of ingested polyphenols to the
      body and the brain, and the means by which bioavailability may be improved by
      specifically designing synergies between orally consumed polyphenols.

PMID- 19841962
TI  - Reversible cardiomyopathy in an adolescent with idiopathic aortic cusp
      ventricular tachycardia.
AB  - This report describes the case of an asymptomatic patient with a ventricular
      tachycardia-induced cardiomyopathy that resolved completely after successful
      radiofrequency ablation. This type of presentation and outcome has not been
      reported in the pediatric literature.

PMID- 19841963
TI  - Effect of transcatheter occlusion of a pulmonary arteriovenous fistula on the
      cardiopulmonary response to exercise.

PMID- 19841964
TI  - Coronary arteriovenous fistula: direct connection of the proximal circumflex
      artery to the coronary sinus.

PMID- 19841965
TI  - Clinical improvement after banding of a pulmonary branch artery in a symptomatic
      patient with Osler-Rendu-Weber syndrome.
AB  - We report a symptomatic newborn with Osler-Rendu-Weber syndrome, multiple and
      diffuse pulmonary arteriovenous malformations, and right-to-left shunting in the
      left lung. Right-to-left shunting was significantly decreased by selectively
      banding the left pulmonary branch artery and clipping one large feeding vessel so
      that total resection of the left lung could be avoided.

PMID- 19841966
TI  - Oral ibuprofen and ductus arteriosus closure in full-term neonates: a prospective
      case-control study.
AB  - Management of patent ductus arteriosus (PDA) in full-term neonates remains
      controversial. We evaluated the effects of oral ibuprofen on PDA closure in 51
      full-term neonates. All neonates were >3-days-old and had a gestational age > or
      = 37 weeks. Patients with ductal-dependent congenital heart disease or severe
      pulmonary artery hypertension (gradient >40 mmHg) were excluded. Patients were
      randomly assigned to the treatment group (n = 30) or the control group (n = 21).
      The treated group received ibuprofen suspension (initially 10 mg/kg, then two 5
      mg/kg doses 24 h apart), and control neonates received a placebo. Physicians who
      treated the patients were blinded to group assignment. There was a statistically
      significant difference in the closure rate of PDA between the treated (73.3%) and
      control groups (42.9%, P = 0.029). Among neonates with PDA closure, there was a
      significant difference in the day of closure between the two groups (25.49 and
      17.65% on the days 4 and 14 after diagnosis of PDA in treated neonates versus
      1.96 and 15.69% in controls, respectively). This study showed the efficacy of
      oral ibuprofen in achieving earlier closure of PDA in full-term neonates.

PMID- 19841967
TI  - Intrapericardial teratoma in a newborn.

PMID- 19841968
TI  - Breast augmentation, antibiotic prophylaxis, and infection: comparative analysis
      of 1,628 primary augmentation mammoplasties assessing the role and efficacy of
      antibiotics prophylaxis duration.
AB  - BACKGROUND: Infections after augmentation mammoplasty are not uncommon, and
      prophylactic antibiotics are routinely administered to minimize infection.
      However, there is paucity of information on the relationship between the length
      of prophylaxis cover and its benefits in primary augmentation mammoplasty. A
      retrospective analysis of different antibiotic cover regimens, their
      effectiveness in preventing infections, and the management of infection in
      established cases is reviewed. METHODS: A retrospective chart analysis of
      periprosthetic infections in primary augmentation mammoplasties performed over
      the past 10 years was conducted. Periprosthetic infection was determined by the
      presence of pain, swelling, redness, and discharge. Each breast was taken as an
      individual unit in 1,628 patients, and data for 3,256 breasts were analyzed. The
      patients had their augmentation in the partial submuscular plane (214 breasts in
      107 patients), the subglandular plane (1,548 breasts in 774 patients), and the
      muscle-splitting biplane (1,494 breasts in 747 patients). All the patients had
      soft round cohesive gel silicone implants. Of the 3,256 implants, 3,218 were
      textured, and 38 were smooth surfaced. The patients received antibiotics as a
      single intravenous dose of cephalosporin (474 breasts in 237 patients), a single
      intravenous dose plus an oral dose for 24 h (344 breasts in 172 patients), or a
      single intravenous dose plus an oral course for 5 days (2,438 breasts in 1,219
      patients). Infection was recorded as superficial (e.g., wound breakdown, stitch
      extrusion, stitch abscess) or deep (periprosthetic). The patients with
      established periprosthetic infections, determined clinically by the presence of
      pain, discharge, swelling, and redness of the breasts, were managed either
      conservatively using antibiotics, passive wound drainage, and healing of the
      wound with secondary intention or by explantation and replacement after 3 to 4
      months. In selected cases of periprosthetic infection, the implants were removed
      after a course of antibiotics and negative swab cultures. The cavity was washed
      thoroughly with betadine and saline, and new implants were simultaneously
      reimplanted. RESULTS: The incidence of infection was lowest with a single
      perioperative dose of intravenous antibiotic compared with a combination of
      intravenous and oral antibiotics. Superficial infection was seen in 38 breasts
      (all unilateral), with an incidence of 1.2%, and periprosthetic infection was
      observed in 17 breasts (13 unilateral and 2 bilateral), giving an infection
      incidence of 0.52% (p = 0.002). In patients with a single intravenous dose of
      antibiotic, superficial and periprosthetic infection was seen in four breasts
      (0.8%) and no breasts, respectively. The difference was not significant (p =
      0.13). The patients receiving a single intravenous antibiotic and a 24-h oral
      antibiotic had superficial and periprosthetic infection rates of 2.3% (8 breasts)
      and 0.3% (1 breast), respectively, and the difference between the two sub-groups
      was significantly higher (p = 0.04). The patients receiving an intravenous
      antibiotic and 5 days of oral antibiotics had superficial and periprosthetic
      infection rates of 1.1% (26 breasts) and 0.65% (14 breasts), respectively. The
      difference between the two subgroups was not significant (p = 0.09). Of the 17
      periprosthetic infections in 15 patients (13 unilateral and 2 bilateral), 11
      breasts (1 bilateral and 9 unilateral) were treated conservatively using
      antibiotics, passive drainage, and wound healing with secondary intention.
      Capsular contracture developed in two of the conservatively treated breasts,
      requiring capsulotomies with change of implants. Of the six periprosthetic
      infections in six patients, requiring surgical intervention, two implants were
      treated using explantation with immediate replacement after a course of
      antibiotics and a negative culture, and two implants were explanted followed by
      reimplantation later. One patient had both implants removed after unilateral
      infection, and no reimplantation was performed. One patient had a bilateral
      infection. In this case, one implant was explanted and the other was treated
      conservatively. The patient had bilateral reimplantion 6 months later, and
      bilateral Baker 4 capsular contracture developed in both breasts within 6 months.
      No other complications were seen in the patients who underwent surgery.
      CONCLUSION: A single dose of intravenous antibiotic is adequate for prophylaxis
      in breast augmentation surgery, and the extra duration of antibiotic cover does
      not result in reduced superficial or periprosthetic infections. Infection can be
      managed in more than one way depending on the nature, degree, and extent of
      infection.

PMID- 19841969
TI  - Silicone nipple shields: an innovative postoperative dressing technique after
      nipple reconstruction.
AB  - BACKGROUND: The newly reconstructed nipple is extremely sensitive to mechanical
      pressure and shearing forces, which can cause flap necrosis and sloughing of the
      skin, eventually promoting infection. Current available dressing solutions are
      cumbersome, inefficient, displeasing, or otherwise not readily obtainable.
      METHODS: In this study, 10 patients with newly reconstructed nipples were
      instructed to use breastfeeding nipple shields as the sole means of nipple
      dressing after the reconstruction procedure. RESULTS: No complications were
      observed overall. Patients reported full adherence to the postoperative dressing
      regimen as well as ease of use, availability, low costs, and pleasing aesthetic
      appearance under garments. DISCUSSION: Silicone breastfeeding nipple shields
      offer an efficient, affable, cheap, widely available, and aesthetically pleasing
      form of postoperative dressing for reconstructed nipples. Their use may enhance
      patient compliance with the dressing regimen and lower the postoperative
      complication rate.

PMID- 19841971
TI  - Protecting the geyser basins of Yellowstone National Park: toward a new national
      policy for a vulnerable environmental resource.
AB  - Geyser basins provide high value recreation, scientific, economic and national
      heritage benefits. Geysers are globally rare, in part, because development
      activities have quenched about 260 of the natural endowment. Today, more than
      half of the world's remaining geysers are located in Yellowstone National Park,
      northwest Wyoming, USA. However, the hydrothermal reservoirs that supply
      Yellowstone's geysers extend well beyond the Park borders, and onto two "Known
      Geothermal Resource Areas"-Island Park to the west and Corwin Springs on the
      north. Geysers are sensitive geologic features that are easily quenched by nearby
      geothermal wells. Therefore, the potential for geothermal energy development
      adjacent to Yellowstone poses a threat to the sustainability of about 500 geysers
      and 10,000 hydrothermal features. The purpose here is to propose that Yellowstone
      be protected by a "Geyser Protection Area" (GPA) extending in a 120-km radius
      from Old Faithful Geyser. The GPA concept would prohibit geothermal and large
      scale groundwater wells, and thereby protect the water and heat supply of the
      hydrothermal reservoirs that support Yellowstone's geyser basins and important
      hot springs. Proactive federal leadership, including buyouts of private
      groundwater development rights, can assist in navigating the GPA through the
      greater Yellowstone area's "wicked" public policy environment. Moreover, the
      potential impacts on geyser basins from intrusive research sampling techniques
      are considered in order to facilitate the updating of national park research
      regulations to a precautionary standard. The GPA model can provide the basis for
      protecting the world's few remaining geyser basins.

PMID- 19841972
TI  - Use of a peripherally inserted central catheter as a conduit for central venous
      access across thrombosed great veins.
AB  - This report describes a technique of inserting an implantable venous access port
      (portacath) through a thrombosed and occluded vein employing a pre-existing
      peripherally inserted central catheter (PICC) as the route of access. The PICC
      was used as a conduit for venous access in a way that has not been described
      previously in the literature. This procedure was performed in a young patient
      with cystic fibrosis in an effort to prevent the use of his virgin contralateral
      veins, which might be used in the future.

PMID- 19841973
TI  - Safety and efficacy assessment of flow redistribution by occlusion of
      intrahepatic vessels prior to radioembolization in the treatment of liver tumors.
AB  - We evaluated the feasibility, safety, and efficacy of radioembolization
      (administered from one or two vascular points) after the redistribution of
      arterial blood flow in the liver in patients with hepatic neoplasms and arterial
      anatomic peculiarities (AAP). Twenty-four patients with liver neoplasms and AAP
      (graded according to Michel's classification) were included in the study. During
      pretreatment angiographic planning, all extrahepatic vessels that could feed the
      tumor were embolized and the intrahepatic vessels occluded in order to
      redistribute blood flow. The distribution of microspheres was initially assessed
      by using technetium-99m-labeled macroaggregated albumin ((99m)Tc-MAA) from one of
      two vascular points before the administration of yttrium-90 ((90)Y)-radiolabeled
      resin microspheres. Perfusion of lesions situated in the redistributed segments
      (L-RS) and nonredistributed segments (L-NRS) were compared by assessing the
      distribution of (99m)Tc-MAA by SPECT/CT. Perfusion was graded as normal, reduced,
      or absent. (90)Y resin microspheres were then injected from the same arterial
      sites as (99m)Tc-MAA and the tumor response recorded 3 months later. The tumor
      response in L-RS was compared with that in L-NRS and graded as better, similar,
      or worse. Among 11 patients with type I AAP in whom mainly vessels in segments I
      III or IV were occluded, perfusion of L-RS was graded as similar (n = 7) or
      reduced (n = 4). Among the remaining 13 patients with AAP types III (n = 3), V (n
      = 4), VIII (n = 3), and others (n = 3) in which aberrant arteries were occluded,
      perfusion of L-RS was graded as similar (n = 9), reduced (n = 3), or absent (n =
      1). Overall, (99m)Tc-MAA was present in the L-RS of 95.8% patients and the
      distribution of (99m)Tc-MAA in L-RS and L-NRS were graded as similar in 66.6% of
      patients. Compared with lesions in the L-NRS, tumor response in L-RS was similar
      in 23 cases and worse in 1 case. No complications were recorded after the
      administration of (90)Y resin microspheres. Redistribution of flow in L-RS is
      feasible and enables a safe and effective delivery of (90)Y resin microspheres
      that are able to be distributed via intrahepatic collaterals and access the
      microvasculature of L-RS.

PMID- 19841974
TI  - Rapid detection of virulence-associated genes in environmental strains of Vibrio
      cholerae by multiplex PCR.
AB  - Vibrio cholerae, the causative agent of cholera is ubiquitously distributed in
      aquatic environment particularly in coastal waters, estuaries, and rivers. In the
      present investigation, a multiplex PCR assay was developed for the detection of
      virulence-associated genes (rtxA, tcpA, ctxA, hlyA, and sto) in environmental
      isolates of V. cholerae. A total of 90 strains isolated from different
      environmental sources were screened for the presence of virulence-associated
      genes. Our results showed that this method represents a simple, cost effective,
      and robust tool for rapid detection of virulence-associated genes. This multiplex
      PCR can be used for examining prevalence of virulence-associated genes and hence
      will be useful for better understanding of epidemiology of environmental V.
      cholerae.

PMID- 19841975
TI  - Potentially pathogenic acanthamoeba isolated from a hospital in Brazil.
AB  - Studies on free-living amoebae (FLA), has been increased in recent years,
      especially related to the genus Acanthamoeba, because these organisms are widely
      found in the environment. The present work isolated and characterized this
      organism from biofilms and dust in hospital environment. 135 samples were
      collected in 15 different environments in a hospital at the south of Brazil.
      Thirty-one (23%) isolates were identified as morphologically belonging to the
      Acanthamoeba genus and 10 of these were submitted to temperature and
      osmotolerance tests as criterion for evaluation of the viability and
      pathogenicity. The tests indicate that four (40%) of these isolates could be
      potentially pathogenic because grew at high temperature (40 degrees C) and
      osmolarity (mannitol 1 M). Some isolates genotypes were determined after
      ribosomal DNA sequencing. These data revealed that three dust isolates belong to
      T4, two biofilm isolates to T5 and one dust isolate to T3 genotype. Therefore,
      Acanthamoeba found in the hospital environment represents a risk for people that
      circulate there.

PMID- 19841976
TI  - Functional identification of a putative beta-galactosidase gene in the special
      lac gene cluster of Lactobacillus acidophilus.
AB  - The putative beta-galactosidase gene (lacZ) of Lactobacillus acidophilus has a
      very low degree of homology to the Escherichia coli beta-galactosidase gene
      (lacZ) and locates in a special lac gene cluster which contains two beta
      galactosidase genes. No functional characteristic of the putative beta
      galactosidase has been described so far. In this study, the lacZ gene of L.
      acidophilus was hetero-expressed in E. coli and the recombinant protein was
      purified by a three-step procedure. The product of the lacZ gene was also
      extracted from L. acidophilus ATCC 4356 and active staining was carried out. The
      enzymatic properties of the purified recombinant LacZ were assayed. The results
      of hetero-expression showed the recombinant LacZ without tag had beta
      galactosidase activity. The purified recombinant LacZ had a specific activity of
      43.2 U/mg protein. The result of active staining showed that the functional
      product of the lacZ gene did exist in L. acidophilus. The L. acidophilus beta
      galactosidase (LacZ) had an optimal pH of 6, an optimal temperature of 37 degrees
      C and could hydrolyze 73% of lactose in milk in 30 h at 10 degrees C. The L.
      acidophilus beta-galactosidase (LacZ) was identified as cold-adapted beta
      galactosidase in this study for the first time, and may be useful for lactose
      removal from dairy products at low temperatures.

PMID- 19841977
TI  - Role of the calcium-binding residues Asp231, Asp233, and Asp438 in alpha-amylase
      of Bacillus amyloliquefaciens as revealed by mutational analysis.
AB  - Role of the calcium-binding residues Asp231, Asp233, and Asp438 of Bacillus
      amyloliquefaciens alpha-amylase (BAA) on the enzyme properties was investigated
      by site-directed mutagenesis. The calcium-binding residues Asp231, Asp233, and
      Asp438 were replaced with Asn, Asn, and Gly to produce the mutants D231N, D233N,
      and D438G, respectively. The mutant amylases were purified to homogeneity and the
      purified enzymes was estimated to be approximately 58 kDa. The specific activity
      for the mutant enzyme D233N was decreased by 84.8%, while D231N and D438G showed
      a decrease of 6.3% and 3.5% to that of the wild-type enzyme, respectively. No
      significant changes in the K (m) value, thermo-stability, optimum temperature,
      and optimum pH were observed in the mutations of D231N and D438G, while
      substitution of Asp233 with Asn resulted in a dramatic reduction in the value of
      catalytic efficiency (K (cat)/K (m)) and thermo-stability at 60 degrees C. The
      ranges of optimum temperature and optimum pH for D233N were also reduced to about
      10 degrees C and 3-4 units, respectively.

PMID- 19841978
TI  - Don't worry, we have a new weapon against cancer!

PMID- 19841979
TI  - E2F1 expression predicts outcome in Korean women who undergo surgery for breast
      carcinoma.
AB  - BACKGROUND: The transcriptional factors E2F1 and E2F2 have been reported to be
      associated with improved chemosensitivity in various cancers. We aimed to
      investigate whether E2F1 and E2F2 can be used as predictors of chemosensitivity
      in hormone-receptor-negative breast cancers (HRNBCs), which are common in Korean
      women. METHODS: A total of 183 patients with primary breast cancer who had
      undergone surgical resection were evaluated on the basis of hormonal status, age,
      histological subtype and grade, tumor size, lymph node metastasis, and stage. The
      immunohistochemical expressions of E2F1 and E2F2 were analyzed for these
      histopathological data and patient survival. RESULTS: E2F1 expression was
      associated with low histological grade (grade 1) and larger tumor size (>2 cm),
      while E2F2 expression was correlated only with large tumor size (>2 cm). The E2F1
      positive group had less tumor recurrences, lymph node metastases during follow
      up, and distant metastases than the E2F1-negative group; E2F1 expression was
      found to be an independent predictive factor of more favorable survival among
      HRNBC patients on univariate and multivariate analyses, but E2F2 expression was
      not. CONCLUSIONS: E2F1 may be a potential prognostic and predictive factor for
      clinical outcome and therapeutic results following adjuvant chemotherapy in HRNBC
      patients.

PMID- 19841980
TI  - Targeting gastric cancer with trastuzumab: new clinical practice and innovative
      developments to overcome resistance.

PMID- 19841981
TI  - Surgery for gastrointestinal stromal tumors of the duodenum.
AB  - BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) represent a unique
      dilemma with varied surgical treatment options. However, the impact of operative
      methods on disease recurrence has never been addressed. METHODS: We
      retrospectively reviewed the medical records of all patients with duodenal GISTs
      treated at our hospital from January 2001 to December 2008. RESULTS: Of the 25
      patients included for analysis, 9 had pancreaticoduodenectomy (PD) and 16 had
      limited operation. Comparison of clinicopathological data between tumors treated
      by PD and by limited operation showed no significant differences in patient age,
      sex, symptoms, location of tumor, tumor grade, immunohistochemical staining
      pattern, or complications after surgery. However, patients with tumors >5 cm (P =
      0.005) or not diagnosed as GISTs before surgery (P = 0.004) were significantly
      more frequently treated by PD. In multivariable analysis, the only significant
      predictor for disease recurrence was high-risk duodenal GISTs. CONCLUSIONS: Based
      on the fact that type of operation was not correlated to operative risk and
      disease recurrence, limited operation rather than PD should be attempted for
      duodenal GIST without involvement of papilla of Vater to preserve more pancreas
      parenchyma, duodenum, and common bile duct.

PMID- 19841982
TI  - Immediate microsurgical reconstruction after tumor ablation predicts survival
      among patients with head and neck carcinoma.
AB  - BACKGROUND: The purpose of this study was to examine whether or not immediate
      microvascular free flap reconstruction influences survival among treated patients
      suffering from oral squamous cell carcinoma (OSCC), controlling for demographic,
      clinical, and tumor characteristics. METHODS: 773 patients with OSCC were treated
      with curative intent. Two hundred and seventy-four patients were immediately
      reconstructed using free microsurgical flaps. All measures were collected by
      chart abstraction. Kaplan-Meier plots and univariate log-rank test and
      multivariate Cox proportional hazards regression models were used to determine
      the association between possible predictor variables and survival time. In
      addition, a randomized matched-pair analysis was conducted to compensate
      different patient cohorts. RESULTS: After controlling for age, tumor stage, nodal
      stage, and tumor grade, which were independent and dependent predictors of
      survival, microsurgical free flap reconstruction was associated with survival
      [hazard ratio (HR) = 0.66, P < 0.001, 95% confidence interval (CI), 0.52 to
      0.83]. In the randomized matched-pair analysis this effect became more evident
      (HR = 0.58, P < 0.001, 95% CI, 0.44 to 0.75). Controlling for extent of tumor,
      only T3 and T4 tumors were significantly associated with survival (P < 0.001, HR
      = 0.46, 95% CI, 0.31 to 0.69) when the area of defect was reconstructed, whereas
      in T1 and T2 tumors no significance was noted (P = 0.08, HR = 0.74, 95% CI, 0.53
      to 1.04). CONCLUSIONS: Reconstruction of defects, especially in patients
      presenting with higher tumor stages, is not associated with shorter overall
      survival rates, as revealed in this study, and should be considered when
      functional deficits due to tumor ablation can be expected postoperatively.

PMID- 19841983
TI  - Different patterns of lymphatic spread of sigmoid, rectosigmoid, and rectal
      cancers.

PMID- 19841984
TI  - Limitations of isolated tumor cells in gastric cancer: heterogeneity requests
      systems biology approaches towards personalized medicine.

PMID- 19841985
TI  - Complete femoral nerve resection with soft tissue sarcoma: functional outcomes.
AB  - BACKGROUND: The functional consequences of resecting the femoral nerve in
      conjunction with soft tissue sarcoma management are not well described. In
      comparison, sciatic nerve involvement by sarcoma was once considered an
      indication for amputation, but sciatic resection is now commonly performed as
      part of a limb-salvage approach. We compared functional outcomes following
      resection of either the femoral or sciatic nerve in patients with soft tissue
      sarcoma. We also compared both groups with patients with large thigh sarcomas
      without nerve involvement. METHODS: The prospectively collected database from a
      tertiary referral center for sarcomas was retrospectively reviewed to identify
      all patients with resection of the femoral nerve performed during wide excision
      of a soft tissue sarcoma. Patient demographics, treatment, complications, and
      functional outcomes in the form of the Musculoskeletal Tumor Society (MSTS) 1987
      score, MSTS 1993 score, and Toronto Extremity Salvage Score (TESS) were
      collected. Control groups of sarcoma patients with sciatic nerve resection in the
      thigh as well as similarly sized tumors in the quadriceps requiring no nerve
      resections were also analyzed. RESULTS: Ten patients with femoral nerve
      resections were identified, all women, aged 47-78 years, with large soft tissue
      sarcomas of varied subtypes. All patients received adjuvant radiotherapy, most
      preoperatively. Six patients developed fractures during long-term follow-up, four
      in nonirradiated portions of the skeleton but directly from falls related to
      absent active knee extensors, and two at least partially attributable to sequelae
      of radiation. MSTS 1987 hip scores demonstrated one excellent, four good, and
      five fair results. MSTS 1993 hip scores averaged 71.4 +/- 17.2% and TESS averaged
      61.7 +/- 21.8. There were no significant differences between the functional
      scores for patients with femoral or sciatic nerve resections (P = 1.0).
      CONCLUSIONS: Femoral nerve resection appears more morbid than anticipated. The
      falls to which patients were prone, even years after surgery, subject them to
      ongoing long-term risks for fractures and other injuries. These nerve-specific
      functional implications should be considered when counseling patients in
      preparation for possible resection of the femoral nerve when it is directly
      involved by a soft tissue sarcoma.

PMID- 19841986
TI  - Molecular characterization of chronic obstructive pulmonary disease-related non
      small cell lung cancer through aberrant methylation and alterations of EGFR
      signaling.
AB  - BACKGROUND: The aim of this study was to evaluate the molecular influence of
      chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small
      cell lung cancer (NSCLC). MATERIALS AND METHODS: The methylation profiles of 12
      genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were
      determined for samples from 229 NSCLC patients. In addition, protein expression
      of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of
      COPD. RESULTS: IL-12Rbeta2 and Wif-1 methylation and HER2 overexpression were
      more frequent events in the COPD group. Eighty nonmalignant lung tissues had no
      correlation with any molecular changes between the COPD and the non-COPD group.
      EGFR mutation was significantly higher in the non-COPD group, while EGFR
      expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated
      SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a
      negative prognostic factor, while methylation of p16(INK4A) and WNT antagonist
      genes was a negative prognostic factor in the non-COPD group. CONCLUSIONS: Novel
      characteristics of COPD-related NSCLC were identified by examination of
      methylation profiles and alterations of EGFR signaling. In consideration of the
      high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a
      distinct population of smoke-related NSCLC, the genetic profile of which is quite
      different from non-COPD NSCLC.

PMID- 19841987
TI  - Oscillations in an intra-host model of Plasmodium Falciparum malaria due to cross
      reactive immune response.
AB  - We consider an intra-host model of malaria that allows for antigenic variation
      within a single species. More specifically, the host's immune response is
      compartmentalized into reactions to major and minor epitopes. We investigate the
      conditions that lead to transient oscillations, which correspond to recurrent
      clinical episodes of the diseases, and how a small delay in the activation of the
      immune response can lead to persistent oscillations. We find that the efficacies
      of the immune responses to the major and minor epitopes, defined in terms of rate
      constants, play a crucial role in determining when there will be transient
      oscillations. The delay necessary to excite persistent oscillations, the time
      duration between disease episodes and their severity are also expressed in terms
      of the immune response efficacies. In addition, we describe how the severity and
      duration of the oscillations depend upon the parasite propagation rates and the
      immune response efficacies.

PMID- 19841988
TI  - Can superselective embolization be definitive for colonic diverticular
      hemorrhage? An institution's experience over 9 years.
AB  - INTRODUCTION: Superselective mesenteric embolization is effective in arresting
      colonic diverticular hemorrhage with minimal complications, but long-term results
      are lacking. We aimed to review the short- and long-term outcome of
      superselective embolization in arresting colonic diverticular hemorrhage in an
      Asian population. METHODS: A retrospective review of all patients who underwent
      superselective embolization for bleeding colonic diverticula from December 2000
      to March 2009 was performed. These cases were drawn from a database of
      embolization for active gastrointestinal hemorrhage. Short-term outcomes (< or
      =30 days from procedure) identified included rebleeding, ischemia, or any further
      intervention for any of these two complications. Readmission for rebleeding
      and/or definitive surgery after 30 days (long-term outcome) was also documented.
      RESULTS: Twenty-three patients, median age 65 years (range 41-79 years), formed
      the study group. Nineteen (82.6%) patients had active hemorrhage from right
      colonic diverticula while four (17.4%) had left-sided diverticular bleeding.
      Technical success was achieved in all 23 (100%) patients. SHORT-TERM OUTCOME:
      Five (21.7%) patients rebled within the same admission, and all underwent
      surgery. One patient perished from ensuing anastomotic dehiscence and septic
      shock and accounted for the only mortality (4.3%) in our series. There was no
      patient with ischemic complications. Another two (8.7%) patients underwent
      elective surgical resection on the advice of their surgeons in the absence of
      rebleeding. LONG-TERM OUTCOME: The median follow-up was 40 months (5-99 months).
      Of the remaining 16 (69.6%) patients for whom the procedure was definitive
      initially, four (25.0%) rebled within 2 years from the primary procedure, and
      elective surgery was performed in one of them. Another had repeat embolization,
      while the other two were successfully managed conservatively. These three
      patients refused surgical intervention. One patient was lost to follow-up, and
      the remaining 11 patients had no further complications. CONCLUSION:
      Superselective embolization for active colonic diverticular hemorrhage is safe
      and effective and should be considered as a first line treatment if possible and
      available. The procedure could act as a bridge to a subsequent more definitive
      elective surgery or be definitive as seen in over 50% of our patients over a
      period of 40 months.

PMID- 19841989
TI  - Risk factors for anastomotic leakage following intersphincteric resection for
      very low rectal adenocarcinoma.
AB  - BACKGROUND: The aim of this study was to perform a retrospective analysis of the
      risk factors for anastomotic leakage following intersphincteric resection (ISR)
      for very low rectal cancer. METHODS: Between 1993 and 2007, 120 patients with T1
      T3 rectal adenocarcinomas located 1 to 5 cm (median 3 cm) from the anal verge
      underwent ISR without radiotherapy. Univariate and multivariate analyses of 47
      prospectively recorded parameters were conducted. RESULTS: All patients had total
      mesorectal excision after complete bowel preparation. Of them, 103 underwent
      partial resection, and 17 underwent complete resection of the internal sphincter.
      Some 108 patients had a defunctioning stoma. Morbidity and mortality rates were
      33% and 0.8%, respectively. Fifteen patients (13%) developed clinical leakage,
      and six (5%) had severe leakage causing relaparotomy, permanent stoma, or death.
      Univariate analysis of risk factors for clinical leakage revealed tumor
      annularity, intraoperative blood transfusion, and pulmonary disease to be
      significant. Multivariate analysis showed transfusion (hazard ratio, 6.5 [95%
      confidence interval, 1.4 to 30]; p = 0.018) and pulmonary disease (6.3 [1.6 to
      26]; p = 0.009) to be independently significant. Moreover, transfusion (71 [3.0
      to 1000]; p = 0.008), colonic J-pouch (32 [1.8 to 500]; p = 0.018), and pulmonary
      disease (32 [1.1 to 1000]; p = 0.044) were independently associated with severe
      leakage. CONCLUSIONS: This study suggests intraoperative blood transfusion and
      pulmonary disease as independent risk factors for clinical and severe leakage
      following ISR and colonic J-pouch as that for severe leakage. By considering
      these factors, we may be able to stratify high-risk patients and prepare
      countermeasures.

PMID- 19841990
TI  - Reconstruction following the pylorus preserving Whipple resection: PJ, HJ, and
      DJ.
AB  - INTRODUCTION: Pancreaticoduodenectomy is one of the most challenging procedures
      performed by general surgeons. DISCUSSION: Many studies have been performed
      looking at the technical aspects of reconstruction after pancreaticoduodenal
      resection. Multiple randomized trials have failed to convincingly demonstrate the
      superiority of any single approach or technique. Here, we illustrate our approach
      to reconstruction, with an emphasis on technical aspects and details. CONCLUSION:
      The fine points can help avoid technical errors that result in anastomotic
      failure.

PMID- 19841991
TI  - Metabolic syndrome and insulin resistance in subjects with morbid obesity.
AB  - BACKGROUND: There is evidence that a group of subjects with obesity fits the
      characteristics of metabolically healthy but obese population. We aimed to assess
      the prevalence of the metabolic syndrome (MS) in nondiabetic subjects with morbid
      obesity (body mass index (BMI) > or = 40 kg/m2) and its correlation with insulin
      resistance. METHODS: We analyzed the data of 211 patients (55 males and 156
      females) with morbid obesity and without overt diabetes, consecutive referred for
      weight loss management. All subjects underwent an oral glucose tolerance test,
      and insulin resistance was calculated by the homeostasis model assessment (HOMA)
      at baseline and by the oral glucose insulin sensitivity (OGIS) during the glucose
      and insulin curve. Clinical and biochemical features of MS were also determined.
      RESULTS: The criteria for MS were fulfilled in 74% of cases, and 10 patients had
      obesity as the sole feature. HOMA-R was normal in 26% of cases, whereas, OGIS was
      normal only in three females. HOMA-R and OGIS significantly differed in relation
      to the presence of MS, and a trend was observed in both tests as function of the
      number of factors of MS (P < 0.001). At logistic regression analysis, after
      adjustment for age, sex, BMI at age 20 years, present BMI, and waist
      circumference, OGIS was the only parameter of insulin resistance significantly
      associated with MS (odds ratio, 2.42; 95% confidence interval, 1.63-3.60).
      CONCLUSIONS: A small number of metabolically healthy, but obese cases exist also
      in the subgroup of patients with morbid obesity in which insulin resistance
      maintains its pivotal role.

PMID- 19841993
TI  - Variation of outcome in weight loss with band volume adjustments under clinical
      and radiological control following laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Following laparoscopic adjustable gastric banding (LAGB), patients
      usually undergo follow-up (FU) to optimize weight loss and detect complications,
      with band-volume adjustment performed either under radiological or clinical
      guidance with no current consensus on what is the best standard of care. We,
      therefore, analyzed our patient cohort to identify differences between the two,
      if any, over a 3-year period. METHODS: We retrospectively reviewed our obesity
      surgery database to find all LAGB patients and grouped them based on method of FU
      without weight exclusions. We then selected out 70 consecutive patients from each
      cohort from an arbitrary time-point to achieve sufficient FU and analyzed the
      results from the data collated. Patients with postoperative complications were
      excluded to prevent bias. RESULTS: From 2003 to 2007, there were 865 LAGB
      performed in our unit. We identified 70 consecutive patients from January 2004
      from each cohort. After review and exclusions, we were left with 50 patients in
      the radiology group (RG) and 49 in the clinical group (CG) [median BMI 43.8 and
      47.1, respectively; median age 43 years in both]. Routine FU was at weekly, then
      fortnightly, and monthly intervals, but results were analyzed at 3-month
      intervals until the first year and every 12 months until the third year. The
      median percentage of excessive weight loss was 22% and 36% at 6 months; 28% and
      43% at 12 months; 27% and 47% at 2 years; and 33% and 46% at 3 years in the RG
      and CG, respectively. There was no difference in difficulties to band fill in
      either group as per clinical records, although there was a greater incidence of
      port damage in the CG. CONCLUSIONS: Our study suggests that at medium-term follow
      up, clinical fill is superior to radiological FU at least in terms of weight
      loss, with the added benefit of avoiding unnecessary radiation albeit that the
      difference between the two methods gets smaller with FU beyond 2 years. This
      topic merits a future randomized control trial to make recommendations without
      biases inherent to retrospective analysis.

PMID- 19841994
TI  - Massive weight loss without surgery in a super obese patient.
AB  - Large weight losses are rarely achieved through non-surgical procedures, but are
      also possible without professional help. A massive weight loss may be complicated
      by the development of an eating disorder psychopathology, followed by weight
      regain. We report the case of a male patient with super obesity (BMI, 86.2
      kg/m(2)), who achieved a massive weight loss (170 kg in 2 years) largely without
      professional help and without surgery. The final body weight (~ 100 kg; BMI,
      32.6) has now been maintained for nearly 2 years. After weight loss, the patient
      had massive skin redundancy in several areas including the breasts, arms,
      abdomen, back, and thighs and a true body weight probably in the normal range.
      All laboratory tests were normal, with the exception of low free testosterone.
      Sonographic examination showed gall bladder microlithiasis. No eating disorders
      and other axis I and axis II psychiatric disorders were present. The case
      illustrates how much weight loss and weight-loss maintenance can be exceptionally
      achieved without surgery and without developing an eating disorder of clinical
      severity or other psychiatric disorders.

PMID- 19841995
TI  - Internal rotation deficits affect scapular positioning in baseball players.
AB  - BACKGROUND: Anecdotal evidence suggests an association between glenohumeral
      internal rotation deficits (GIRD) and scapular dysfunction, an observable
      alteration in the normal position or motion of the scapula in relation to the
      thoracic cage. QUESTIONS/PURPOSES: We therefore hypothesized players with GIRD
      (15 degrees or greater) will have decreased dominant arm scapular upward rotation
      and increased scapular protraction compared with baseball players with GIRD (14
      degrees or less). METHODS: We studied 43 baseball players with no current
      shoulder or elbow symptoms; 22 had GIRD 15 degrees or greater and 21 had GIRD 14
      degrees or less. We measured glenohumeral internal rotation supine with the
      scapula stabilized. Scapular upward rotation was tested at rest; 60 degrees , 90
      degrees , and 120 degrees abduction in the scapular plane; and scapular
      protraction at 0 degrees , hands on hips, and 90 degrees abduction in the
      scapular plane. RESULTS: The GIRD (15 degrees or greater) group had less scapular
      upward rotation at 60 degrees (3.58), 90 degrees (5.01), and 120 degrees (2.63)
      in the dominant arm. Scapular protraction at 90 degrees (0.88 cm) also was
      greater in the dominant arm of the GIRD (15 degrees or greater) group.
      CONCLUSIONS: Baseball players with more GIRD have alterations to the position and
      motion of their scapula. A dual goal of minimizing GIRD and strengthening the
      scapular stabilizers may be warranted in this population. LEVEL OF EVIDENCE:
      Level II, prognostic study. See Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 19841996
TI  - Commentary of "Brown Gould B, Graybiel AM. Afferents to the cerebellar cortex in
      the cat: evidence for an intrinsic pathway leading from the deep nuclei to the
      cortex. Brain Research 1976;110:601-611".

PMID- 19841997
TI  - Difficult tracheal intubation in randomized controlled studies: ethical
      considerations.

PMID- 19841998
TI  - Confronting inequities in Latino health care.

PMID- 19841999
TI  - Perceived quality of care, receipt of preventive care, and usual source of health
      care among undocumented and other Latinos.
AB  - BACKGROUND: Latinos are the largest minority group in the United States and
      experience persistent disparities in access to and quality of health care.
      OBJECTIVES: (1) To determine the relationship between nativity/immigration status
      and self-reported quality of care and preventive care. (2) To assess the impact
      of a usual source of health care on receipt of preventive care among Latinos.
      DESIGN: Using cross-sectional data from the 2007 Pew Hispanic Center/Robert Wood
      Johnson Foundation Hispanic Healthcare Survey, a nationally representative
      telephone survey of 4,013 Latino adults, we compared US-born Latinos with foreign
      born Latino citizens, foreign-born Latino permanent residents and undocumented
      Latinos. We estimated odds ratios using separate multivariate ordered logistic
      models for five outcomes: blood pressure checked in the past 2 years, cholesterol
      checked in the past 5 years, perceived quality of medical care in the past year,
      perceived receipt of no health/health-care information from a doctor in the past
      year, and language concordance. RESULTS: Undocumented Latinos had the lowest
      percentages of insurance coverage (37% vs 77% US-born, P < 0.001), usual source
      of care (58% vs 79% US-born, P < 0.001), blood pressure checked (67% vs 87% US
      born, P < 0.001), cholesterol checked (56% vs 83% US-born, P < 0.001), and
      reported excellent/good care in the past year (76% vs 80% US-born, P < 0.05).
      Undocumented Latinos also reported the highest percentage receiving no
      health/health-care information from their doctor (40% vs 20% US-born, P < 0.001)
      in the past year. Adjusted results showed that undocumented status was associated
      with lower likelihood of blood pressure checked in the previous 2 years (OR =
      0.60; 95% CI, 0.43-0.84), cholesterol checked in the past 5 years (OR = 0.62; 95%
      CI, 0.39-0.99), and perceived receipt of excellent/good care in the past year (OR
      = 0.56; 95% CI, 0.39-0.77). Having a usual source of care increased the
      likelihood of a blood pressure check in the past 2 years and a cholesterol check
      in the past 5 years. CONCLUSION: In this national sample, undocumented Latinos
      were less likely to report receiving blood pressure and cholesterol level checks,
      less likely to report having received excellent/good quality of care, and more
      likely to receive no health/health-care information from doctors, even after
      adjusting for potential confounders. Our study shows that differences in
      nativity/immigration status should be taken into consideration when we discuss
      perceived quality of care among Latinos.

PMID- 19842000
TI  - Latino access to the patient-centered medical home.
AB  - BACKGROUND: Disparities can be caused by minorities receiving care in low-quality
      settings. The patient-centered medical home (PCMH) has been identified as a model
      of high-quality primary care that can eliminate disparities. However, Latinos are
      less likely to have PCMHs. OBJECTIVE: To identify Latino subgroup variations in
      having a PCMH, its impact on disparities, and to identify factors associated with
      Latinos having a PCMH. DESIGN: Analysis of the 2005 MEPS Household Component, a
      nationally representative survey with an oversample of Latino adults. The total
      sample was 24,000 adults, including 6,200 Latinos. MEASUREMENTS: The PCMH was
      defined as having a regular provider, who provides total care, fosters patient
      engagement in care, and offers easy access to care. Self reports of preventive
      care (cholesterol screening, blood pressure check, mammography, and prostate
      specific antigen screening) and patient experiences were examined. RESULTS: White
      (57.1%) and Puerto Rican (59.3%) adults were most likely to have a PCMH, while
      Mexican/Mexican Americans (35.4%) and Central and South Americans (34.2%) were
      least likely. Much of the disparity was caused by lack of access to a regular
      provider. Respondents with a PCMH had higher rates of preventive care and
      positive patient experiences. Disparities in care were eliminated or reduced for
      Latinos with PCMHs. The regression models showed private insurance, which is less
      common among all Latinos, was an important predictor of having a PCMH.
      CONCLUSIONS: Eliminating health-care disparities will require assuring access to
      the PCMH. Addressing differences in health-care coverage that contribute to lower
      rates of Latino access to the PCMH will also reduce disparities.

PMID- 19842001
TI  - Predictors of hypertension awareness, treatment, and control among Mexican
      American women and men.
AB  - BACKGROUND: The burden of hypertension and related health care needs among
      Mexican Americans will likely increase substantially in the near future.
      OBJECTIVES: In a nationally representative sample of U.S. Mexican American adults
      we examined: 1) the full range of blood pressure categories, from normal to
      severe; 2) predictors of hypertension awareness, treatment and control and; 3)
      prevalence of comorbidities among those with hypertension. DESIGN: Cross
      sectional analysis of pooled data from the National Health and Nutrition
      Examination Surveys (NHANES), 1999-2004. PARTICIPANTS: The group of participants
      encompassed 1,359 Mexican American women and 1,421 Mexican American men, aged 25
      84 years, who underwent a standardized physical examination. MEASUREMENTS:
      Physiologic measures of blood pressure, body mass index, and diabetes.
      Questionnaire assessment of blood pressure awareness and treatment. RESULTS:
      Prevalence of Stage 1 hypertension was low and similar between women and men (
      approximately 10%). Among hypertensives, awareness and treatment were suboptimal,
      particularly among younger adults (65% unaware, 71% untreated) and those without
      health insurance (51% unaware, 62% untreated). Among treated hypertensives,
      control was suboptimal for 56%; of these, 23% had stage >/=2 hypertension.
      Clustering of CVD risk factors was common; among hypertensive adults, 51% of
      women and 55% of men were also overweight or obese; 24% of women and 23% of men
      had all three chronic conditions-hypertension, overweight/obesity and diabetes.
      CONCLUSION: Management of hypertension in Mexican American adults fails at
      multiple critical points along an optimal treatment pathway. Tailored strategies
      to improve hypertension awareness, treatment and control rates must be a public
      health priority.

PMID- 19842002
TI  - Diabetes awareness and knowledge among Latinos: does a usual source of healthcare
      matter?
AB  - OBJECTIVE: To provide national prevalence estimates of usual source of healthcare
      (USHC), and examine the relationship between USHC and diabetes awareness and
      knowledge among Latinos using a modified Andersen model of healthcare access.
      PARTICIPANTS: Three thousand eight hundred and ninety-nine Latino (18-years or
      older) participants of the Pew Hispanic Center/Robert Wood Johnson Foundation
      Hispanic/Latino Health survey from the 48 contiguous United States. DESIGN: Cross
      sectional, stratified, random sample telephone interviews. METHODS: Self-reported
      healthcare service use was examined in regression models that included a past
      year USHC as the main predictor of diabetes awareness and knowledge. Anderson
      model predisposing and enabling factors were included in additional statistical
      models. RESULTS: Significant differences in USHC between Latino groups were found
      with Mexican Americans having the lowest rates (59.7%). USHC was associated with
      significantly higher diabetes awareness and knowledge (OR=1.24; 95%CI=1.05-1.46)
      after accounting for important healthcare access factors. Men were significantly
      (OR=0.64; 95%CI=0.52-0.75) less informed about diabetes than women. CONCLUSION:
      We found important and previously unreported differences between Latinos with a
      current USHC provider, where the predominant group, Mexican Americans, are the
      least likely to have access to a USHC. USHC was associated with Latinos being
      better informed about diabetes; however, socioeconomic barriers limit the
      availability of this potentially valuable tool for reducing the risks and burden
      of diabetes, which is a major public health problem facing Latinos.

PMID- 19842003
TI  - The role of patient activation on patient-provider communication and quality of
      care for US and foreign born Latino patients.
AB  - BACKGROUND: Previous research has shown positive effects of patient activation on
      healthcare outcomes, but there is practically no information on the
      generalization of these findings for Latino patients. Little data are available
      on whether patient activation is associated with healthcare outcomes for Latino
      patients and whether activation varies by language proficiency and nativity
      status. OBJECTIVE: We examined the levels of activation by characteristics of
      Latino patients (e.g. nativity, language, health status). We investigated whether
      patient activation relates to the quality of care received and enhanced doctor
      patient communication for Latino patients. DESIGN: We conducted analyses of 1,067
      US born and foreign born Latinos who participated in the second wave of the
      PEW/RWJF Hispanic Healthcare Survey during 2008. PARTICIPANTS: Participants were
      self-identified Latinos (18+) with a doctor visit, living in the contiguous
      United States who could be contacted by telephone. RESULTS: US born Latinos had
      significantly (P < 0.001) greater patient activation scores than foreign born
      Latinos (75 versus 70). Latinos classified as bilingual and those reporting
      excellent health evidenced higher mean activation scores as compared to Spanish
      speaking Latinos and those reporting fair or poor health. After adjusting for
      demographics, health status, other language and service use factors, patient
      activation was strongly associated with self-reported quality of care and better
      doctor-patient communication among both US and foreign born Latino respondents.
      CONCLUSIONS: Interventions that augment patient activation could increase quality
      of care and improved patient-provider communication, potentially reducing health
      care disparities for Latinos.

PMID- 19842004
TI  - The role of spirituality healing with perceptions of the medical encounter among
      Latinos.
AB  - BACKGROUND: Little is known about the relationship between spirituality healing
      and perceptions about the medical encounter among Latinos. OBJECTIVES: To examine
      the association between spirituality healing and attitudes of self-reported
      perceptions about the medical encounter. DESIGN: A cross-sectional telephone
      survey. PARTICIPANTS: 3,728 Latinos aged >or=18 years residing in the United
      States from Wave 1 of the Pew Hispanic Center/Robert Wood Johnson Foundation
      Latino Health Survey. MEASUREMENTS: Dependent variables were ever prayed for
      healing (yes/no), ever asked others to pray for healing (yes/no), considered
      important spiritual healing (very vs. somewhat or not important), and ever
      consulted a 'curandero' (folk healer in Latin America) (yes/no). The primary
      independent variables were feelings about the last time seeing a Doctor (confused
      by information given, or frustrated by lack of information) and perception of
      quality of medical care (excellent, good, fair or poor) within the past 12
      months. RESULTS: Six percent of individuals reported that they had ever consulted
      a curandero, 60% prayed for healing, 49% asked others to pray for healing, and
      69% considered spiritual healing as very important. In multivariable analyses,
      feeling confused was associated with increased odds of consulting a curandero (OR
      = 1.58; 95% CI, 1.02-2.45), praying for healing (OR = 1.30; 95% CI, 1.03-1.64),
      asking others to pray for healing (OR = 1.29; 95% CI, 1.03-1.62), and considering
      spiritual healing as very important (OR = 1.30; 95% CI, 1.01-1.66). Feeling
      frustrated by a lack of information was associated with asking others to pray for
      healing (OR = 1.29; 95% CI, 1.04-1.60). A better perception of quality of medical
      care was associated with lower odds of consulting a curandero (OR = 0.83; 95% CI,
      0.70-0.98). CONCLUSION: Feelings about the medical encounter were associated with
      spirituality healing, praying for healing, and asking others to pray for healing.
      Feeling confused and perception of poor quality of medical care were associated
      with consulting a curandero.

PMID- 19842005
TI  - Perceived discrimination and self-reported quality of care among Latinos in the
      United States.
AB  - BACKGROUND: Given the persistence of health and health-care disparities among
      Latinos in the United States and evidence that discrimination affects health and
      health care, an investigation of the relationship between perceived
      discrimination and quality of health care among Latinos is warranted. OBJECTIVE:
      To examine the relationship of perceived discrimination (in general and in regard
      to doctors and medical personnel) with self-reported quality of health care and
      doctor-patient communication in a nationally representative Latino population
      sample. PARTICIPANTS: Participants were 1,067 Latino adults aged >or=18 years
      living in the US selected via random-digit dialing. Telephone interviews were
      conducted in 2008 during Wave 2 of the Pew Hispanic Center/Robert Wood Johnson
      Foundation Hispanic Healthcare Survey. RESULTS: US-born Latinos were twice as
      likely to report general discrimination as foreign born: 0.32 SD versus -0.23 SD
      (P < 0.001) on the Detroit Area Survey (DAS) discrimination scale. Higher DAS
      discrimination was associated with lower self-reported quality of care in US-born
      Latinos [OR = 0.5; 95% CI (0.3, 0.9); P = 0.009]. For foreign-born Latinos,
      report of any doctor or medical staff discrimination was associated with lower
      quality of care [OR = 0.5; 95% CI (0.3, 0.9); P = 0.03], but the DAS was not. For
      US-born Latinos, doctor discrimination and higher DAS were jointly associated
      with worse doctor-patient communication. For foreign-born Latinos, the effect of
      discrimination on doctor-patient communication was significantly smaller than
      that observed in US-born Latinos. CONCLUSIONS: Given the association between
      perceived discrimination and quality of care, strategies to address
      discrimination in health-care settings may lead to improved patient satisfaction
      with care and possibly to improved treatment outcomes.

PMID- 19842006
TI  - Effects of health insurance on perceived quality of care among Latinos in the
      United States.
AB  - BACKGROUND: There is suggestive evidence that lower rates of health insurance
      coverage increases the gaps in quality and access to care among Latinos as
      compared with non-Latino whites. In order to examine these potential disparities,
      we assessed the effects of insurance coverage and multiple covariates on
      perceived quality of care. OBJECTIVE: To assess the distribution of perceived
      quality of care received in a national Latino population sample, and the role of
      insurance in different patient subgroups. DESIGN: Telephone interviews conducted
      between 2007 and 2008 using the Pew Hispanic Center/Robert Wood Johnson
      Foundation Latino Health Surveys (Waves 1 and 2). PARTICIPANTS: Randomly selected
      Latino adults aged >or=18 years living in the United States. MEASUREMENTS:
      Pearson chi(2) tests identified associations among various demographic variables
      by quality of care ratings (poor, fair, good, excellent) for the insured and
      uninsured (Wave 1: N = 3545). Subgroup analyses were conducted among Wave 2
      participants reporting chronic conditions (N = 1067). Bivariate and multivariate
      analyses were conducted to estimate the effects of insurance, demographic
      variables and consumer characteristics on quality of care. RESULTS: Insurance
      availability had an odds ratio of 1.47 (95% CI, 1.22-1.76) net of confounders in
      predicting perceived quality of care among Latinos. The largest gap in rates of
      excellent/good ratings occurred among the insured with eight or more doctor
      visits compared to the uninsured (76.2% vs. 54.6%, P < .05). CONCLUSIONS: Future
      research can gain additional insights by examining the impact of health insurance
      on processes of care with a refined focus on specific transactions between
      consumers and providers' support staff and physicians guided by the principles of
      patient-centered care.

PMID- 19842007
TI  - Heterogeneity in health insurance coverage among US Latino adults.
AB  - OBJECTIVE: We sought to determine the differences in observed and unobserved
      factors affecting rates of health insurance coverage between US Latino adults and
      US Latino adults of Mexican ancestry. Our hypothesis was that Latinos of Mexican
      ancestry have worse health insurance coverage than their non-Mexican Latino
      counterparts. METHODS: The National Health Interview Survey (NHIS) database from
      1999-2007 consists of 33,847 Latinos. We compared Latinos of Mexican ancestry to
      non-Mexican Latinos in the initial descriptive analysis of health insurance
      coverage. Disparities in health insurance coverage across Latino categories were
      later analyzed in a multivariable logistic regression framework, which adjusts
      for confounding variables. The Blinder-Oaxaca technique was applied to parse out
      differences in health insurance coverage into observed and unobserved components.
      RESULTS: US Latinos of Mexican ancestry consistently had lower rates of health
      insurance coverage than did US non-Mexican Latinos. Approximately 65% of these
      disparities can be attributed to differences in observed characteristics of the
      Mexican ancestry population in the US (e.g., age, sex, income, employment status,
      education, citizenship, language and health condition). The remaining disparities
      may be attributed to unobserved heterogeneity that may include unobserved
      employment-related information (e.g., type of employment and firm size) and
      behavioral and idiosyncratic factors (e.g., risk aversion and cultural
      differences). CONCLUSIONS: This study confirmed that Latinos of Mexican ancestry
      were less likely to have health insurance than were non-Mexican Latinos.
      Moreover, while differences in observed socioeconomic and demographic factors
      accounted for most of these disparities, the share of unobserved heterogeneity
      accounted for 35% of these differences.

PMID- 19842008
TI  - Diversity, health, and the state of patient care in the US health care system.

PMID- 19842009
TI  - Postconditioning with levosimendan reduces the infarct size involving the PI3K
      pathway and KATP-channel activation but is independent of PDE-III inhibition.
AB  - Reperfusion injury is strongly involved in the loss of functional heart tissue in
      patients after acute myocardial infarction. Various signal transduction pathways
      to reduce infarct size during reperfusion have been characterized. However, so
      far in the clinical setting no standard therapies are applied due to the lack of
      suitable drugs. Levosimendan, a calcium sensitizer, has been shown to improve
      survival in cardiogenic shock after infarction. Focus of the present study was to
      address the question, whether a bolus application of levosimendan prior to
      reperfusion is able to reduce the infarct size. A well-characterized model, the
      in vivo rat model, was used and levosimendan applied 5 min prior to reperfusion
      after 30-min occlusion of the left coronary artery followed by a 30-min
      reperfusion period. This pharmacological postconditioning was compared to the
      ischemic postconditioning with three times occlusion/reperfusion periods of 30 s
      each. To further address the question if in this in vivo model the
      phosphatidylinositol 3-kinase (PI3K) pathway may be involved, the PDE-III
      inhibiting property of levosimendan was compared to the PDE-III inhibitor
      enoximone. Ischemic postconditioning significantly reduced the infarct size from
      48 +/- 2 to 32 +/- 1% of the area at risk (P < 0.05). Similarly, levosimendan
      decreased infarct size down to 29 +/- 3%. The combination of ischemic
      postconditioning and pharmacological postconditioning using levosimendan did not
      result in a further reduction of the infarct size. Both, the mitochondrial KATP
      channel blocker 5-hydroxydecanoate (5-HD) and the PI3K inhibitor wortmannin
      abolished the protection afforded by levosimendan completely, while the
      inhibitors alone did not influence the infarct size in control hearts.
      Pharmacological postconditioning with enoximone did not result in any infarct
      size reduction. Postconditioning with levosimendan significantly increased the
      phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3beta (GSK
      3beta) at 5 min of reperfusion, an effect which could be blocked completely by
      the additional administration of wortmannin. In conclusion, levosimendan applied
      prior to reperfusion in acute myocardial infarction significantly reduces the
      infarct size in an in vivo rat model. This protection involves the PI3K pathway
      and the activation of mitochondrial KATP-channels, but is independent of PDE-III
      inhibition. This finding may open new possibilities for the treatment of patients
      with acute myocardial infarction using levosimendan, which is an already
      established therapy in cardiogenic shock. Whether the reduction of mortality in
      cardiogenic shock by levosimendan may in part be based on this postconditioning
      effect remains to be elucidated in clinical setting.

PMID- 19842010
TI  - Two subgroups of schizophrenia identified by systematic cognitive
      neuropsychiatric mapping.
AB  - The description of the heterogeneous phenomenological, pathophysiological, and
      etiological nature of schizophrenia is under way; however, the relationships
      between heterogeneity levels are still unclear. We performed a robust cross
      sectional study, including a systematic neuropsychological battery, assessment of
      clinical symptoms, neurological soft signs, morphogenetic anomalies and smell
      identification, and measurement of event-related potentials on 50 outpatients
      with schizophrenia in their compensated states. An explorative fuzzy cluster
      analysis revealed two subgroups in this sample that could be distinguished from
      each other on symptomatological, cognitive and neurological levels. The patterns
      of cognitive dysfunctions and neurological developmental anomalies equally
      indicate that there may be hemispherical differences between the patients
      belonging to the different clusters.

PMID- 19842011
TI  - Modafinil for Parkinson's disease fatigue.
AB  - Fatigue is common in Parkinson's disease (PD), occurring in up to 42% of patients
      (2). There is no recognized treatment. This is a study of modafinil for
      Parkinson's disease related fatigue. Ethical approval was given. Patients with
      idiopathic PD were recruited from a Movement Disorders clinic. Those with
      depression, dementia, and other causes for fatigue were excluded. Patients were
      assessed using the Fatigue Severity Scale (FSS), Hospital Anxiety and Depression
      Scale (HADS), self-rating of improvement, Epworth Sleepiness Scale (ESS), and
      UPDRS. Modafinil was titrated up over 4 weeks to maximum of 400 mg/day. There
      followed a 5 week maintenance phase before reassessment. Thirteen patients
      participated. No significant change was seen in any safety measure. The FSS did
      not change significantly, however those on modafinil rated an improvement in
      their fatigue compared to placebo. The Modafinil group had a statistically
      significant improvement on ESS (p < 0.05). This is a small study of modafinil in
      selected PD patients. There is a suggestion of improvement on the global clinical
      impression scale for fatigue, but no significant change on FSS. A larger study is
      needed to further evaluate this drug in PD fatigue. This study highlights the
      problems with recruitment when trialing treatments of non-motor symptoms in PD. A
      significant improvement in EDS was seen.

PMID- 19842013
TI  - Cognitive performance in hypotensive persons with spinal cord injury.
AB  - BACKGROUND: Due to sympathetic de-centralization, individuals with spinal cord
      injury (SCI), especially those with tetraplegia, often present with hypotension,
      worsened with upright posture. Several investigations in the non-SCI population
      have noted a relationship between chronic hypotension and deficits in memory,
      attention and processing speed and delayed reaction times. OBJECTIVE: To
      determine cognitive function in persons with SCI who were normotensive or
      hypotensive over a 24-h observation period while maintaining their routine
      activities. METHODS: Subjects included 20 individuals with chronic SCI (2-39
      years), 13 with tetraplegia (C4-8) and 7 with paraplegia (T2-11). Individuals
      with hypotension were defined as having a mean 24-h systolic blood pressure (SBP)
      below 110 mmHg for males and 100 mmHg for females, and having spent >or=50% of
      the total time below these gender-specific thresholds. The cognitive battery used
      included assessment of memory (CVLT), attention and processing speed (Digit Span,
      Stroop word and color and Oral Trails A), language (COWAT) and executive function
      (Oral Trails B and Stroop color-word). RESULTS: Demographic parameters did not
      differ among the hypotensive and normotensive groups; the proportion of
      individuals with tetraplegia (82%) was higher in the hypotensive group. Memory
      was significantly impaired (P < 0.05) and there was a trend toward slowed
      attention and processing speed (P < 0.06) in the hypotensive compared to the
      normotensive group. INTERPRETATION: These preliminary data suggest that chronic
      hypotension in persons with SCI is associated with deficits in memory and
      possibly attention and processing speed, as previously reported in the non-SCI
      population.

PMID- 19842014
TI  - Brassinosteroids protect Lycopersicon esculentum from cadmium toxicity applied as
      shotgun approach.
AB  - Surface-sterilized seeds of two tomato cultivars (cv. K-25 and Sarvodya) were
      soaked in 100 microM CdCl(2) for 8 h (shotgun approach). The resulting 59-day-old
      seedlings were sprayed with 10(-8) M of 28-homobrassinolide (HBL) or 24
      epibrassinolide (EBL) to their foliage. Both cultivars showed significantly
      different response to Cd stress. Cadmium severely restricted the growth,
      photosynthetic efficiency, and activity of nitrate reductase (E.C. 1.6.6.1) and
      carbonic anhydrase (E.C. 4.2.1.1) in Sarvodya as compared to K-25. However, the
      activities of antioxidative enzymes were significantly higher in K-25. This
      result may be considered an indication of better tolerance of the K-25 cultivars
      to Cd stress. Moreover, the spray of both the brassinosteroids (HBL/EBL) were
      found very effective in neutralizing the adverse effects generated by metals that
      reflect in better photosynthetic performance by the cultivars. An interesting
      aspect of this study is that HBL or EBL spray caused a further increase in
      proline content and antioxidative enzyme activities, which were already enhanced
      by Cd stress. This effect of brassinosteroids (HBL/EBL) was more pronounced in K
      25 than in Sarvodya, representing the tolerance and adoptable behavior of K-25.

PMID- 19842015
TI  - Effect and mechanism of AR-6 in experimental rheumatoid arthritis.
AB  - The root of Clematis chinensis Osbeck has been used widely in rheumatoid
      arthritis in Chinese traditional medicine and AR-6 is a triterpene saponin
      isolated from it. In this present study, we investigated in vivo effects of oral
      AR-6 in chronic rat adjuvant-induced arthritis (AA) and in vitro effect in
      macrophage and synoviocytes cells. Arthritic scores and serum inflammatory
      mediators were evaluated 19 days after AA induction by endermic injection of
      Freund's complete adjuvant in Sprague-Dawley(S-D) rats. Oral administration of AR
      6 to arthritic rats resulted in a clear decrease of clinical signs compared to
      untreated controls. The synoviocyte and macrophage response ex vivo were then
      analyzed. Anti-arthritic effects of AR-6 correlated with significant decrease of
      NO and TNF-alpha produced by peritoneal macrophages, ex vivo and in vitro. AR-6
      also significant decreased the proliferation of synoviocyte. These data indicate
      that AR-6 is a potential anti-inflammatory therapeutic and preventive agent.

PMID- 19842016
TI  - Supercritical phase inversion of starch-poly(epsilon-caprolactone) for tissue
      engineering applications.
AB  - In this work, a starch-based polymer, namely a blend of starch-poly(epsilon
      caprolactone) was processed by supercritical assisted phase inversion process.
      This processing technique has been proposed for the development of 3D structures
      with potential applications in tissue engineering applications, as scaffolds. The
      use of carbon dioxide as non-solvent in the phase inversion process leads to the
      formation of a porous and interconnected structure, dry and free of any residual
      solvent. Different processing conditions such as pressure (from 80 up to 150 bar)
      and temperature (45 and 55 degrees C) were studied and the effect on the
      morphological features of the scaffolds was evaluated by scanning electron
      microscopy and micro-computed tomography. The mechanical properties of the SPCL
      scaffolds prepared were also studied. Additionally, in this work, the in vitro
      biological performance of the scaffolds was studied. Cell adhesion and
      morphology, viability and proliferation was assessed and the results suggest that
      the materials prepared are allow cell attachment and promote cell proliferation
      having thus potential to be used in some for biomedical applications.

PMID- 19842017
TI  - Infection in fracture fixation: can we influence infection rates through implant
      design?
AB  - Musculoskeletal infection is one of the most common complications associated with
      surgical fixation of bones fractured during trauma. These infections usually
      involve bacterial colonisation and biofilm formation on the fracture fixation
      device itself, as well as infection of the surrounding tissues. Antibiotic
      prophylaxis, wound debridement and postsurgical care can reduce the incidence of,
      but do not prevent, these infections. Much research and development has been
      focussed on ways to further reduce the incidence of infection and in the
      following short review we describe our experiences investigating the contribution
      of the basic design of fracture fixation devices on the susceptibility to
      infection. It has been shown in animal studies that device size, shape, mode of
      action and material and topography play an interrelated role in the
      susceptibility to infection. Although direct extrapolation from animal studies to
      the clinical setting is difficult, close consideration of the design factors that
      can reduce the incidence of infection in animal models is expected to help
      minimise the incidence of infection associated with any clinically implemented
      fracture fixation device.

PMID- 19842018
TI  - Apatite-forming ability of Ti-15Zr-4Nb-4Ta alloy induced by calcium solution
      treatment.
AB  - Ti-15Zr-4Nb-4Ta alloy free from cytotoxic elements shows high mechanical strength
      and high corrosion resistance. However, simple NaOH and heat treatments cannot
      induce its ability to form apatite in the body environment. In the present study,
      this alloy was found to exhibit high apatite-forming ability when it was treated
      with NaOH and CaCl(2) solutions, and then subjected to heat and hot water
      treatments to form calcium titanate, rutile, and anatase on its surface. Its high
      apatite-forming ability was maintained even in 95% relative humidity at 80
      degrees C after 1 week. The surface layer of the treated alloy had scratch
      resistance high enough for handling hard surgical devices. Thus, the treated
      alloy is believed to be useful for orthopedic and dental implants.

PMID- 19842019
TI  - A bioactive polymer grafted on titanium oxide layer obtained by electrochemical
      oxidation. Improvement of cell response.
AB  - The anchorage failure of titanium implants in human body is mainly due to
      biointegration problem. The proposed solution is to graft a bioactive polymer at
      the surface of the implant in order to improve and control the interactions with
      the living system. In this paper, we describe the grafting of poly sodium styrene
      sulfonate on titanium surface by using a silanization reaction. The key point is
      to increase the TiOH content at the surface of the implant which can react with
      methoxy silane groups of 3-methacryloxypropyltrimethoxysilane (MPS). Two
      procedures were used: chemical oxidation and electrochemical oxidation. The last
      oxidation procedure was carried out in two different electrolytes: oxalic acid
      and methanol. These different oxidation methods allow controlling the roughness
      and the depth of the oxide layer. The methacryloyl group of MPS grafted at the
      titanium surface by silanization reaction is copolymerized with sodium styrene
      sulfonate using a thermal initiator able to produce radicals by heating.
      Colorimetric method, ATR-FTIR, XPS techniques and contact angle measurements were
      applied to characterize the surfaces. MG63 osteoblastic cell response was studied
      on polished, oxidized and grafted titanium samples. Cell adhesion, Alkaline
      Phosphatase activity and calcium nodules formation were significantly enhanced on
      grafted titanium surfaces compared to un-modified surfaces.

PMID- 19842021
TI  - Preparation, characterization and evaluation of targeting potential of
      amphotericin B-loaded engineered PLGA nanoparticles.
AB  - PURPOSE: The objective of present work was to develop a mannose-anchored,
      engineered nanoparticulate system for efficient delivery of amphotericin B to
      macrophages. Furthermore, the effect of spacer on macrophage targeting was also
      evaluated. METHODS: PLGA was conjugated to mannose via direct coupling (M-PLGA)
      and via PEG spacer (M-PEG-PLGA), and engineered PLGA nanoparticles (M-PNPs and M
      PEG-PNPs) were prepared from respective conjugates. These prepared engineered
      PNPs were characterized for size, polydispersity index (PDI), surface charge, and
      drug entrapment efficiency (% DEE). Transmission electron microscopy (TEM) and
      atomic force microscopy (AFM) were employed to study the shape and surface
      morphology of engineered PNPs. Macrophage targeting was evaluated via cellular
      uptake, ex vivo antileishmanial activity and in vivo biodisposition pattern of
      engineered PNPs in macrophage-rich organs. RESULTS: The developed engineered PNPs
      were found to be of nanometric size (<200 nm) and to have low PDI (<0.162) and
      good entrapment efficiency (%DEE >53.0%). AFM and TEM revealed that both M-PNPs
      and M-PEG-PNPs had smooth surface and spherical topography. Engineered PNPs with
      spacer showed enhanced uptake, potential antileishmanial activity and higher
      disposition in macrophage-rich organs, suggesting improved macrophage targeting.
      CONCLUSIONS: The results suggest that engineering of nanoparticles could lead to
      development of efficient carrier for macrophage targeting.

PMID- 19842022
TI  - Trajectories of life satisfaction across the transition to post-compulsory
      education: do adolescents follow different pathways?
AB  - To examine the developmental trajectories of life satisfaction shown by
      adolescents during a major educational transition, 687 (327 girls, 360 boys)
      Finnish adolescents responded to measures of life satisfaction during the
      beginning of their last year in comprehensive school and three times annually
      thereafter during the transition to post-comprehensive education. Growth Mixture
      Modeling identified three latent groups based on life satisfaction: high
      decreasing (18%), low-increasing (16%), and high-stable (66%). The results showed
      that boys and those with high academic achievement were overrepresented in the
      high-stable life satisfaction group. The results further showed that those with
      high school satisfaction at the last measurement time were more likely to belong
      to the high-stable or low-increasing life satisfaction group. Finally,
      adolescents in the high-stable life satisfaction group were more often on an
      academic track at the last measurement time.

PMID- 19842023
TI  - Nervousness and performance characteristics as predictors of peer behavior
      towards socially anxious adolescents.
AB  - Social anxiety in adolescents has frequently been linked to negative outcomes
      from social interactions. The present study investigated whether socially anxious
      adolescents are treated negatively by their classmates and which characteristics
      of socially anxious adolescents could explain negative social responses.
      Classroom observations of class behavior were made during oral presentations of
      94 students (60% females) in the ages of 13-18 years. Speakers' social
      performance, speech quality, and nervousness during the presentation were also
      rated. Findings showed that the social performance of socially anxious students
      was a predictor of class behavior, whereas their overt nervousness was not.
      Surprisingly, the quality of their speech was negatively related to class
      behavior. Implications of these findings for the treatment of socially anxious
      adolescents are discussed.

PMID- 19842024
TI  - Carbon monoxide liberated from CO-releasing molecule (CORM-2) attenuates
      ischemia/reperfusion (I/R)-induced inflammation in the small intestine.
AB  - CORM-released CO has been shown to be beneficial in resolution of acute
      inflammation. The acute phase of intestinal ischemia-reperfusion (I/R) injury is
      characterized by oxidative stress-related inflammation and leukocyte recruitment.
      In this study, we assessed the effects and potential mechanisms of CORM-2
      released CO in modulation of inflammatory response in the small intestine
      following I/R-challenge. To this end mice (C57Bl/6) small intestine were
      challenged with ischemia by occluding superior mesenteric artery (SMA) for 45
      min. CORM-2 (8 mg/kg; i.v.) was administered immediately before SMA occlusion.
      Sham operated mice were injected with vehicle (0.25% DMSO). Inflammatory response
      in the small intestine (jejunum) was assessed 4 h following reperfusion by
      measuring tissue levels of TNF-alpha protein (ELISA), adhesion molecules E
      selectin and ICAM-1 (Western blot), NF-kappaB activation (EMSA), along with PMN
      tissue accumulation (MPO assay) and leukocyte rolling/adhesion in the
      microcirculation of jejunum (intravital microscopy). The obtained results
      indicate that tissue levels of TNF-alpha, E-selectin and ICAM-1 protein
      expression, activation of NF-kappaB, and subsequent accumulation of PMN were
      elevated in I/R-challenged jejunum. The above changes were significantly
      attenuated in CORM-2-treated mice. Taken together these findings indicate that
      CORM-2-released CO confers anti-inflammatory effects by interfering with NF
      kappaB activation and subsequent up-regulation of vascular pro-adhesive phenotype
      in I/R-challenged small intestine.

PMID- 19842025
TI  - Association of interleukin-8 gene polymorphisms and haplotypes with oral lichen
      planus in a Chinese population.
AB  - Interleukin-8 (IL-8), a CXC chemokine with multiple biological functions, plays
      an important role in the pathogenesis of oral lichen planus (OLP). The aim of
      this study was to investigate the association of single nucleotide polymorphisms
      (SNPs) of IL-8 gene with OLP in a Chinese population. Four SNPs of the IL-8 gene
      at positions -845 T/C (rs2227532), -738 T/A, -251 A/T (rs4073) and +781 C/T
      (rs2227306) were analyzed in 109 patients with OLP and 101 normal controls using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. The data revealed that the -251 AA genotype and -251 A allele frequency
      was significantly lower in the erosive OLP (eOLP) group than in the control group
      (P = 0.012 and P = 0.031, respectively). Haplotype analysis revealed that the 
      251 A/+781 C haplotype frequency was lower in the eOLP group than in the control
      group (P = 0.029) while the -251 T/+781 C haplotype frequency was higher in the
      eOLP patients than in the healthy controls (P = 0.028). The study suggests that
      the IL-8 polymorphisms may be associated with the severity of OLP in this Chinese
      cohort.

PMID- 19842027
TI  - The DSM diagnostic criteria for gender identity disorder in children.
AB  - In this article, I review the diagnostic criteria for Gender Identity Disorder
      (GID) in children as they were formulated in the DSM-III, DSM-III-R, and DSM-IV.
      The article focuses on the cumulative evidence for diagnostic reliability and
      validity. It does not address the broader conceptual discussion regarding GID as
      "disorder," as this issue is addressed in a companion article by Meyer-Bahlburg
      (2009). This article addresses criticisms of the GID criteria for children which,
      in my view, can be addressed by extant empirical data. Based in part on
      reanalysis of data, I conclude that the persistent desire to be of the other
      gender should, in contrast to DSM-IV, be a necessary symptom for the diagnosis.
      If anything, this would result in a tightening of the diagnostic criteria and may
      result in a better separation of children with GID from children who display
      marked gender variance, but without the desire to be of the other gender.

PMID- 19842026
TI  - Gamma-linolenic acid inhibits inflammatory responses by regulating NF-kappaB and
      AP-1 activation in lipopolysaccharide-induced RAW 264.7 macrophages.
AB  - Gamma linolenic acid (GLA) is a member of the n-6 family of polyunsaturated fatty
      acids and can be synthesized from linoleic acid (LA) by the enzyme delta-6
      desaturase. The therapeutic values of GLA supplementation have been documented,
      but the molecular mechanism behind the action of GLA in health benefits is not
      clear. In this study, we assessed the effect of GLA with that of LA on
      lipopolysaccharide (LPS)-induced inflammatory responses and further explored the
      molecular mechanism underlying the pharmacological properties of GLA in mouse RAW
      264.7 macrophages. GLA significantly inhibited LPS-induced protein expression of
      inducible nitric oxide synthase, pro-interleukin-1beta, and cyclooxygenase-2 as
      well as nitric oxide production and the intracellular glutathione level. LA was
      less potent than GLA in inhibiting LPS-induced inflammatory mediators. Both GLA
      and LA treatments dramatically inhibited LPS-induced IkappaB-alpha degradation,
      IkappaB-alpha phosphorylation, and nuclear p65 protein expression. Moreover, LPS
      induced nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) nuclear
      protein-DNA binding affinity and reporter gene activity were significantly
      decreased by LA and GLA. Exogenous addition of GLA but not LA significantly
      reduced LPS-induced expression of phosphorylated extracellular signal-regulated
      kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK)-1. Our data suggest that GLA
      inhibits inflammatory responses through inactivation of NF-kappaB and AP-1 by
      suppressed oxidative stress and signal transduction pathway of ERK and JNK in LPS
      induced RAW 264.7 macrophages.

PMID- 19842028
TI  - The D2 dopamine receptor gene and nicotine dependence among bladder cancer
      patients and controls.
AB  - Multiple twin, family, and genetic studies have rendered substantial evidence
      supporting an association between hereditary factors and smoking initiation and
      maintenance. To investigate further the relationships between the DRD2 genotypes,
      cigarette use and nicotine dependence, we examined the prevalence of
      polymorphisms in the TaqIA (A1 and A2) and the TaqIB (B1 and B2) alleles among a
      series of 608 non-Hispanic White bladder cancer patients and 608 matched
      controls. Among ever-smoking controls, A1 and B1 genotypes exhibited a greater
      smoking intensity and were significantly younger at the age of initiation than
      A2A2 or B2B2 genotypes (two-sided P < 0.05). Among former smoking cases, persons
      with the A1 genotypes exhibited significantly higher mean pack-years and years of
      smoking, and were younger at the age of initiation than were persons with the
      A2A2 genotype (two-sided P < 0.05). Additionally, current smokers with the A1
      genotypes reported fewer quit attempts than those with the A2A2 genotype (two
      sided P < 0.01). The present study suggests that the DRD2 alleles A1 and B1
      confer greater vulnerability to tobacco use.

PMID- 19842030
TI  - Introduction.

PMID- 19842029
TI  - Relations among perceived control over anxiety-related events, worry, and
      generalized anxiety disorder in a sample of adolescents.
AB  - This study examined the associations among perceived control over anxiety-related
      events, worry, and both symptoms and diagnoses of generalized anxiety disorder
      (GAD). The sample was comprised of 140 adolescents (60 girls) between the ages of
      10 and 17 years (M ( age ) = 14.6 years; SD = 2.25) recruited from the general
      community. Findings were consistent with hypotheses. Self-reported perceived
      control over anxiety-related events related negatively to worry as well as
      symptoms and diagnoses of GAD even after accounting for variance associated with
      age, gender, and negative affectivity. Results are discussed in terms of the
      theoretical implications that perceived control over anxiety-related events may
      have for understanding GAD symptomatology among youth.

PMID- 19842031
TI  - Correlation of GREB1 mRNA with protein expression in breast cancer: validation of
      a novel GREB1 monoclonal antibody.
AB  - Studies of gene regulated by estrogen in breast cancer 1 (GREB1) have focused on
      mRNA levels with limited evidence about GREB1 protein expression in normal and
      breast cancer cells. A monoclonal antibody that recognizes GREB1 protein in
      breast tissues could be applied to correlate protein expression with established
      mRNA expression data. A hybridoma expressing a murine monoclonal antibody
      targeting a 119 amino acid peptide specific to human GREB1 was generated. The
      novel monoclonal GREB1 antibody (GREB1ab) was validated for use in Western
      blotting as well as immunohistochemical (IHC) applications. GREB1ab detects a 216
      kDa protein corresponding to GREB1 in estrogen receptor alpha (ERalpha+) breast
      cancer cells as well as ERalpha- breast cancer cells transduced with a GREB1
      expression vector. GREB1ab specificity was verified using an ERalpha antagonist
      to prevent GREB1 induction as well as a silencing siRNA targeting GREB1 mRNA.
      GREB1ab was further validated for detection of GREB1 by IHC in breast cancer cell
      lines and breast tissue microarrays (TMA). ERalpha+ cell lines were observed to
      express GREB1 while ERalpha- cell lines did not express detectable levels of the
      protein. Using breast cancer tissue whole sections, IHC with the GREB1ab
      identified protein expression in ERalpha+ breast cancer tissue as well as normal
      breast tissue, with little GREB1 expression in ERalpha- breast cancer tissue.
      Furthermore, these data indicate that GREB1 mRNA expression correlates well with
      protein expression. The novel monoclonal GREB1ab is specific for GREB1 protein.
      This antibody will serve as a tool for investigations focused on the expression,
      distribution, and function of GREB1 in normal breast and breast cancer tissues.

PMID- 19842033
TI  - Axillary reverse mapping for breast cancer.
AB  - The axillary reverse mapping (ARM) technique has been developed to map and
      preserve arm lymphatic drainage during axillary lymph node dissection (ALND)
      and/or sentinel lymph node (SLN) biopsy, thereby minimizing arm lymphedema.
      However, several problems remain to be resolved in the practical application of
      this technique. This article presents a review of current knowledge regarding ARM
      and discusses the practical applicability and relevance of this technique.
      Identification rates of ARM nodes were insufficient using blue dye. Although this
      was improved using radioisotopes, radioisotopes alone do not permit visual
      mapping of ARM lymphatics. Fluorescence imaging may be useful to improve the
      identification rate of ARM nodes and lymphatics. On the other hand, the ARM nodes
      may be involved with metastatic foci in patients with extensive axillary lymph
      node metastases. Moreover, the SLN draining the breast may be the same as the ARM
      node draining the upper extremity in a minority of patients. These issues
      represent important drawbacks of the ARM procedure. The success of ARM in
      reducing lymphedema has not yet been determined. Further studies are needed
      before this can be accepted as a standard procedure in surgical management of
      breast cancer.

PMID- 19842034
TI  - Adipocyte fatty acid-binding protein as a novel prognostic factor  in obese
      breast cancer patients.
AB  - Several adipocytokines, such as leptin or adiponectin, are associated with
      obesity and the risk for breast cancer. Adiopcyte fatty acid binding-protein(A
      FABP) is another protein found in adipose tissue;therefore, we investigated the
      association of A-FABP with the occurrence and prognosis of breast cancer. In our
      study,200 women attending the University of Ulm for breast surgery between the
      years 2005 and 2007 were included;159 had histologically confirmed breast cancer;
      41 had histologically confirmed benign lesions. Serum levels ofA-FABP, leptin,
      and adiponectin were measured, and their relationship to body-mass-index (BMI),
      breast cancer, and tumor characteristics were analyzed; logistic regression model
      was adjusted to age, BMI, menopausal status, use of Hormone Replacement Therapy
      (HRT), and family history of breast cancer. Serum A-FABP levels were found to be
      significantly higher in obese (BMI C 25) than in non-obese women (BMI B 24.9),
      41.16 ng/ml and 24.95 ng/ml,respectively (P?0.0001). Independent of obesity, the
      serum A-FABP levels were significantly higher in breast cancer patients (34.65
      ng/ml) than in healthy controls(24.47 ng/ml), P?0.0001; the odds ratio (1.038,
      P?0.05,95% confidence interval 1.001-1.72) showed a significant association of A
      FABP with breast cancer risk. Serum leptin levels showed a strong correlation
      with BMI(rs = 0.78) and were significantly higher in breast cancer patients
      (20.87 ng/ml) than in controls (14.90 ng/ml),P?0.05. In contrast, adiponectin
      showed no significant association with breast cancer. Concerning tumor
      characteristics,A-FABP was positively connected with tumor size (T C 2 cm,
      P?0.05) and nodal-status (P?0.05).Our study reveals that high A-FABP serum levels
      are associated with obesity, breast cancer risk, and adverse tumor
      characteristics.

PMID- 19842032
TI  - A hypersensitive estrogen receptor alpha mutation that alters dynamic protein
      interactions.
AB  - Estrogen receptor alpha (ERalpha) is highly regulated through multiple mechanisms
      including cell signaling, posttranslational modifications, and protein-protein
      interactions. We have previously identified a K303R ERalpha mutation within the
      hinge region of ERalpha. This mutation results in an altered posttranslational
      regulation and increased in vitro growth in the presence of low estrogen
      concentrations. We sought to determine if cells expressing this mutant ERalpha
      would display hypersensitive tumor growth in in vivo athymic ovariectomized nude
      mice. MCF-7 cells, stably expressing the K303R ERalpha, formed tumors in nude
      mice faster than cells expressing wild-type ERalpha in the presence of low levels
      of estrogen. When estrogen was withdrawn, all tumors regressed but half of the
      K303R ERalpha-expressing tumors became estrogen-independent and regrew. We
      evaluated potential mechanisms for the observed hypersensitivity. The mutant
      ERalpha did not demonstrate increased estrogen binding affinity, but did exhibit
      increased interactions with members of the SRC family of coactivators. The mutant
      ERalpha demonstrated increased levels and occupancy time on the pS2 promoter. In
      the presence of the K303R ERalpha, the SRC-3 and p300 coactivators also displayed
      increased levels and time on the pS2 promoter. The K303R ERalpha has, in part,
      lost critical negative regulation by the F domain. Collectively, these data
      demonstrate an important role for the K303R ERalpha mutation in hormonal
      regulation of tumor growth and estrogen-regulated promoter dynamics in human
      breast cancer.

PMID- 19842035
TI  - Carrying the burdens of poverty, parenting, and addiction: depression symptoms
      and self-silencing among ethnically diverse women.
AB  - Depression among women commonly co-occurs with substance abuse. We explore the
      association between women's depressive symptoms and self-silencing accounting for
      the effects of known childhood and adult risk indicators. Participants are 233
      ethnically diverse, low-income women who abused alcohol/drugs prenatally.
      Depressive symptomatology was assessed using the Addiction Severity Index.
      Multivariate logistic regression models examined the association between self
      silencing and the dependent depression variable. The full model indicated a 3%
      increased risk for depressive distress for each point increase in self-silencing
      score (OR = 1.03; P = .001). Differences in depressive symptomatology by ethnic
      groups were accounted for by their differences in self-silencing.

PMID- 19842036
TI  - Surveillance for dysplasia in patients with ileal pouch-anal anastomosis for
      ulcerative colitis: an interim analysis.
AB  - BACKGROUND: The risk of developing cancer in the ileal pouch of patients with
      surgery for ulcerative colitis has not been defined. Dysplasia in the pouch is
      quite rare. Although some suggest pouch surveillance based on previous
      histological assessments, there are no guidelines for surveillance of these
      patients. The aim of our study was to investigate that risk and identify time
      intervals for ileoanal pouch surveillance. METHODS: Endoscopy and biopsies of the
      ileal pouch were performed at 3, 6, and/or 12 months after ileal pouch-anal
      anastomosis (IPAA) became functional. Biopsies were evaluated by two pathologists
      using Riddel's criteria. Interim data analysis using descriptive statistics is
      reported. RESULTS: Thirty-eight patients have entered the study. Average patient
      age at 3, 6, and 12 months of surveillance was 39.1, 36.8, and 39.1 years,
      respectively. Average disease duration was 8.2 years. Ten of 38 cases (26%) had
      colonic dysplasia prior to surgery. Dysplasia within the pouch was reported in
      one patient 6 months after IPAA became functional. This patient demonstrated no
      dysplasia at 12 months or statistical divergence by age, duration of disease or
      history of colonic dysplasia prior to IPAA. No subgroup of patients with
      dysplasia was identified to calculate cumulative risk or perform comparative
      statistical analysis. CONCLUSION: A study with longer follow-up after IPAA should
      precede any attempt to recommend routine surveillance. However, the finding of
      dysplasia early after surgery underscores the importance of early pouch
      surveillance in our population, at least until definite predisposing variables
      are identified.

PMID- 19842037
TI  - Promoting a positive transition to parenthood: a randomized clinical trial of
      couple relationship education.
AB  - The transition to parenthood is often associated with a decline in couple
      relationship adjustment. Couples (n = 71) expecting their first child were
      randomly assigned to either: (a) Becoming a Parent (BAP), a maternal parenting
      education program; or (b) Couple CARE for Parents (CCP), a couple relationship
      and parenting education program. Couples were assessed pre-intervention (last
      trimester of pregnancy), post-intervention (5 months postpartum), and follow-up
      (12 months postpartum). Relative to BAP, CCP reduced negative couple
      communication from pre- to post-intervention, and prevented erosion of
      relationship adjustment and self-regulation in women but not men from pre
      intervention to follow-up. Mean parenting stress reflected positive adjustment to
      parenthood with no differences between BAP and CCP. CCP shows promise as a brief
      program that can enhance couple communication and women's adjustment to
      parenthood.

PMID- 19842038
TI  - Enjoyment and its discontents: Ecclesiastes in dialogue with Freud on the
      stewardship of joy.
AB  - The book of Ecclesiastes has frequently been mischaracterized as a cynical or
      pessimistic work. Instead, this article recommends Ecclesiastes, following Eunny
      P. Lee, as contributing to pastoral theology through its embodied and pragmatic
      theology of enjoyment in which practices of joy revitalize the human spirit.
      However, there are some who are unable to experience satisfaction. The absence of
      reflection on this problem in Ecclesiastes scholarship is considered the starting
      point of pastoral theology, and is addressed by a turn to the frequently
      misunderstood passage in 7:16-18, bringing it into conversation with the
      structural [corrected] model of the human person developed by Freud. At the same
      time, the interpersonal aspects of enjoyment found in Ecclesiastes critique Freud
      by suggesting how the fragmented parts of self-experience can be held together in
      an interpersonal context.

PMID- 19842039
TI  - Mouse 3T3-L1 cells acquire resistance against oxidative stress as the adipocytes
      differentiate via the transcription factor FoxO.
AB  - Repression of excessive increase and enlargement of adipocytes that is closely
      associated with obesity is effective in the prevention and treatment of metabolic
      syndrome. Generally, apoptosis is induced in cells via a wide variety of
      intracellular or extracellular substances, and recently, it has been suggested
      that the FoxO subfamily is involved in the induction of apoptosis. We aimed to
      elucidate the mechanism of FoxO-mediated apoptosis-induction in the adipocytes
      under the reactive oxygen species (ROS) stimulus. The treatment of differentiated
      and undifferentiated 3T3-L1 cells with glucose oxidase (GOD), an enzyme that
      generates H(2)O(2), induced apoptosis and led to the accumulation of 8-OHdG.
      Apoptosis analysis revealed that GOD treatment induced apoptosis in
      differentiated 3T3-L1 cells less efficiently than in undifferentiated
      preadipocytes. GOD remarkably increased the levels of Bad, Bax, and Bim-the genes
      that are actively involved in cell apoptosis. GOD treatment also increased the
      expression of FoxO3a mRNA and protein. The introduction of FoxO3a-siRNA into 3T3
      L1 cells suppressed the oxidative stress-induced expression of Bim mRNA, as well
      as the GOD-induced apoptosis. Furthermore, the expression of MnSOD, Cu/ZnSOD, and
      catalase, as well as of FoxO, increased significantly along with the progression
      of adipocyte differentiation. These results indicated that ROS-induced apoptosis
      in undifferentiated 3T3-L1 cells via the expression of FoxO3a, whereas FoxO
      expression suppressed the ROS-induced apoptosis in differentiated 3T3-L1 cells
      via the expression of ROS-scavenging enzymes.

PMID- 19842040
TI  - Apoplexy in non functioning pituitary adenoma after one dose of leuprolide as
      treatment for prostate cancer.
AB  - We report the case of a 60 year old male who complained of headache and blurry
      vision--that progressed to left ophthalmoplegia and ptosis--after receiving a
      dose of leuprolide for Prostate cancer therapy. Imaging showed a hemorrhagic
      sellar mass. The patient underwent transsphenoidal debulking, and the tissue
      obtained demonstrated immunohistochemical staining for LH. A literature review
      revealed nine previously reported cases of pituitary apoplexy after GnRH agonist
      therapy for prostate cancer. In most cases, the sellar tissues stained for LH,
      consistent with a gonadotropinoma. The pathophysiology of these events is
      unclear, but recent animal models suggest possible explanations. The predominance
      of gonadotropinomas is important because they do not usually present with
      hypersecretory symptoms. Particular attention to clinical findings suggestive of
      a non functioning pituitary tumor in patients receiving GnRH agonist therapy is
      critical as routine screening with MRI is not practical.

PMID- 19842041
TI  - Evaluation of griseofulvin binary and ternary solid dispersions with HPMCAS.
AB  - The stability and dissolution properties of griseofulvin binary and ternary solid
      dispersions were evaluated. Solid dispersions of griseofulvin and hydroxypropyl
      methylcellulose acetate succinate (HPMCAS) were prepared using the spray drying
      method. A third polymer, poly[N-(2-hydroxypropyl)methacrylate] (PHPMA), was
      incorporated to investigate its effect on the interaction of griseofulvin with
      HPMCAS. In this case, HPMCAS can form H bonds with griseofulvin directly; the
      addition of PHPMA to the solid dispersion may enhance the stability of the
      amorphous griseofulvin due to greater interaction with griseofulvin. The X-ray
      powder diffraction results showed that griseofulvin (binary and ternary solid
      dispersions) remained amorphous for more than 19 months stored at 85% RH compared
      with the spray-dried griseofulvin which crystallized totally within 24 h at
      ambient conditions. The Fourier transform infrared scan showed that griseofulvin
      carbonyl group formed hydrogen bonds with the hydroxyl group in the HPMCAS, which
      could explain the extended stability of the drug. Further broadening in the peak
      could be seen when PHPMA was added to the solid dispersion, which indicates
      stronger interaction. The glass transition temperatures increased in the ternary
      solid dispersions regardless of HPMCAS grade. The dissolution rate of the drug in
      the solid dispersion (both binary and ternary) has significantly increased when
      compared with the dissolution profile of the spray-dried griseofulvin. These
      results reveal significant stability of the amorphous form due to the hydrogen
      bond formation with the polymer. The addition of the third polymer improved the
      stability but had a minor impact on dissolution.

PMID- 19842042
TI  - Organic-inorganic composites for bone drug delivery.
AB  - This review paper attempts to provide an overview in the fabrication and
      application of organic-inorganic based composites in the field of local drug
      delivery for bone. The concept of local drug delivery exists for a few decades.
      However, local drug delivery in bone and specially application of composites for
      delivery of drugs to bone is an area for potential research interest in the
      recent time. The advantages attained by an organic-inorganic composite when
      compared to its individual components include their ability to release drug,
      adopting to the natural environment and supporting local area until complete bone
      regeneration, which make them carriers of interest for local drug delivery for
      bone.

PMID- 19842043
TI  - Gum arabic-coated magnetic nanoparticles for potential application in
      simultaneous magnetic targeting and tumor imaging.
AB  - Magnetic iron oxide nanoparticles (MNP) coated with gum arabic (GA), a
      biocompatible phytochemical glycoprotein widely used in the food industry, were
      successfully synthesized and characterized. GA-coated MNP (GA-MNP) displayed a
      narrow hydrodynamic particle size distribution averaging about 100 nm; a GA
      content of 15.6% by dry weight; a saturation magnetization of 93.1 emu/g Fe; and
      a superparamagnetic behavior essential for most magnetic-mediated applications.
      The GA coating offers two major benefits: it both enhances colloidal stability
      and provides reactive functional groups suitable for coupling of bioactive
      compounds. In vitro results showed that GA-MNP possessed a superior stability
      upon storage in aqueous media when compared to commercial MNP products currently
      used in magnetic resonance imaging (MRI). In addition, significant cellular
      uptake of GA-MNP was evaluated in 9L glioma cells by electron spin resonance
      (ESR) spectroscopy, fluorescence microscopy, and MRI analyses. Based on these
      findings, it was hypothesized that GA-MNP might be utilized as a MRI-visible drug
      carrier in achieving both magnetic tumor targeting and intracellular drug
      delivery. Indeed, preliminary in vivo investigations validate this clinical
      potential. MRI visually confirmed the accumulation of GA-MNP at the tumor site
      following intravenous administration to rats harboring 9L glioma tumors under the
      application of an external magnetic field. ESR spectroscopy quantitatively
      revealed a 12-fold increase in GA-MNP accumulation in excised tumors when
      compared to contralateral normal brain. Overall, the results presented show
      promise that GA-MNP could potentially be employed to achieve simultaneous tumor
      imaging and targeted intra-tumoral drug delivery.

PMID- 19842045
TI  - Let's not forget tautomers.
AB  - A compound exhibits tautomerism if it can be represented by two structures that
      are related by an intramolecular movement of hydrogen from one atom to another.
      The different tautomers of a molecule usually have different molecular
      fingerprints, hydrophobicities and pKa's as well as different 3D shape and
      electrostatic properties; additionally, proteins frequently preferentially bind a
      tautomer that is present in low abundance in water. As a result, the proper
      treatment of molecules that can tautomerize, approximately 25% of a database, is
      a challenge for every aspect of computer-aided molecular design. Library design
      that focuses on molecular similarity or diversity might inadvertently include
      similar molecules that happen to be encoded as different tautomers. Physical
      property measurements might not establish the properties of individual tautomers
      with the result that algorithms based on these measurements may be less accurate
      for molecules that can tautomerize-this problem influences the accuracy of
      filtering for library design and also traditional QSAR. Any 2D or 3D QSAR
      analysis must involve the decision of if or how to adjust the observed Ki or IC50
      for the tautomerization equilibria. QSARs and recursive partitioning methods also
      involve the decision as to which tautomer(s) to use to calculate the molecular
      descriptors. Docking virtual screening must involve the decision as to which
      tautomers to include in the docking and how to account for tautomerization in the
      scoring. All of these decisions are more difficult because there is no extensive
      database of measured tautomeric ratios in both water and non-aqueous solvents and
      there is no consensus as to the best computational method to calculate tautomeric
      ratios in different environments.

PMID- 19842044
TI  - MicroRNA regulation of cancer stem cells and therapeutic implications.
AB  - MicroRNAs (miRNAs) are a class of endogenous non-protein-coding RNAs that
      function as important regulatory molecules by negatively regulating gene and
      protein expression via the RNA interference (RNAi) machinery. MiRNAs have been
      implicated to control a variety of cellular, physiological, and developmental
      processes. Aberrant expressions of miRNAs are connected to human diseases such as
      cancer. Cancer stem cells are a small subpopulation of cells identified in a
      variety of tumors that are capable of self-renewal and differentiation.
      Dysregulation of stem cell self-renewal is a likely requirement for the
      initiation and formation of cancer. Furthermore, cancer stem cells are a very
      likely cause of resistance to current cancer treatments, as well as relapse in
      cancer patients. Understanding the biology and pathways involved with cancer stem
      cells offers great promise for developing better cancer therapies, and might one
      day even provide a cure for cancer. Emerging evidence demonstrates that miRNAs
      are involved in cancer stem cell dysregulation. Recent studies also suggest that
      miRNAs play a critical role in carcinogenesis and oncogenesis by regulating cell
      proliferation and apoptosis as oncogenes or tumor suppressors, respectively.
      Therefore, molecularly targeted miRNA therapy could be a powerful tool to correct
      the cancer stem cell dysregulation.

PMID- 19842046
TI  - Simple tests for the validation of multiple field spin relaxation data.
AB  - (15)N spin relaxation data is widely used to extract detailed dynamic information
      regarding bond vectors such as the amide N-H bond of the protein backbone.
      Analysis is typically carried using the Lipari-Szabo model-free approach. Even
      though the original model-free equation can be determined from single field R
      (1), R (2) and NOE, over-determination of more complex motional models is
      dependent on the recording of multiple field datasets. This is especially
      important for the characterization of conformational exchange which affects R (2)
      in a field dependent manner. However, severe artifacts can be introduced if
      inconsistencies arise between experimental setups with different magnets (or
      samples). Here, we propose the use of simple tests as validation tools for the
      assessment of consistency between different datasets recorded at multiple
      magnetic fields. Synthetic data are used to show the effects of inconsistencies
      on the proposed tests. Moreover, an analysis of data currently deposited in the
      BMRB is performed. Finally, two cases from our laboratory are presented. These
      tests are implemented in the open-source program relax, and we propose their use
      as a routine check-up for assessment of multiple field dataset consistency prior
      to any analysis such as model-free calculations. We believe this will aid in the
      extraction of higher quality dynamics information from (15)N spin relaxation
      data.

PMID- 19842047
TI  - Multiregional periodic matrix for modeling the population dynamics of sardine
      (Sardina pilchardus) along the moroccan atlantic coast: management elements for
      fisheries.
AB  - In this paper, we present a deterministic time discrete mathematical model based
      on multiregional periodic matrices to describe the dynamics of Sardina pilchardus
      in the Central Atlantic area of the Moroccan coast. This model deals with two
      stages (immature and mature) and three spatial zones where sardines are supposed
      to migrate from one zone to another. The population dynamics is described by an
      autonomous recurrence equation N(t + 1) = A.N(t), where A is a positive matrix
      whose entries are estimated using data collected during biannual acoustic surveys
      carried out from 2001 to 2003 onboard the Norwegian research vessel "Dr Fridtjof
      Nansen". The dominant eigenvalue lambda of A that gives the long-term growth rate
      of fish population is smaller than one. This agrees with the stock decrease
      observed in the data collected. We show that lambda is highly sensitive to the
      recruitment rate and much less sensitive to the reproduction rate. These results
      can clearly be used to define an efficient scenario in order to fight for
      instance against a stock decrease.

PMID- 19842048
TI  - Evaluation of metastatic and angiogenic potentials of human colon carcinoma cells
      in chick embryo model systems.
AB  - Increased metastatic and angiogenic potentials of aggressive human colon
      carcinoma cells were verified in independent chick embryo models by comparing in
      vivo highly metastatic SW620 colon carcinoma cell line with its isogenic, non
      metastatic SW480 cell variant. In the experimental metastasis model, both cell
      types rapidly arrested in the chorioallantoic membrane (CAM) vasculature as
      demonstrated by quantitative PCR and immunohistochemistry. Live cell imaging also
      indicated that both SW620 and SW480 cells efficiently extravasated from the CAM
      capillary system. However, only few SW480 cells were present in the CAM tissue
      after 24-48 h. In contrast, the numbers of SW620 cells increased exponentially,
      indicating proliferative and survival advantages of metastatic colon carcinoma
      cells in vivo. Multicellular SW620 foci were identified in close proximity to CAM
      blood vessels. A positive correlation between increased metastatic ability and
      VEGF-expression of colon carcinoma SW620 cells was demonstrated by the
      substantial inhibitory effects of anti-VEGF treatment on the levels of metastatic
      colonization and density of blood vessels adjacent to tumor cell foci.
      Furthermore, the chick embryo angiogenesis model confirmed high levels of VEGF
      dependent angiogenesis induced by SW620 cells, but not SW480 cells. Thus, chick
      embryo experimental metastasis and CAM angiogenesis models appear to coordinately
      reflect critical features of advanced colon carcinomas, i.e., the acquisition of
      enhanced survival and increased angiogenic potentials, both constituting critical
      determinants of colon cancer progression. The use of rapid and quantitative chick
      embryo models might provide alternative approaches to conventional mammalian
      model systems for screening anti-cancer agents.

PMID- 19842049
TI  - Transesophageal Doppler devices: A technical review.
AB  - Monitoring of aortic blood flow, conducting large portions of the cardiac output
      (CO), allows conclusions on the global hemodynamic status of patients. For this
      purpose, transesophageal Doppler (TED) devices have been developed, which
      interrogate the descending aorta and calculate aortic blood flow velocity using
      the Doppler principle. The recorded velocity-time curve can be used to estimate
      CO as well other advanced hemodynamic parameters such as preload, afterload and
      myocardial contractility. Clinical studies in perioperative patients have
      demonstrated a reduced postoperative morbidity and shorter length of hospital
      stay when TED is used to guide fluid management. However, several assumptions are
      needed to translate the measured Doppler frequency shift to hemo- dynamic
      variables and discrepancies between the assumed and the actual condition may
      introduce a considerable risk for erroneous calculations. A correct
      interpretation of the displayed parameters requires profound knowledge on the
      technical basis of this method as well as its technical limitations. Our review
      focuses on these technical aspects which the clinician should be familiar with to
      allow proper use of TED monitoring devices.

PMID- 19842050
TI  - Family history of cancer and malignant germ cell tumors in children: a report
      from the Children's Oncology Group.
AB  - Family history of testicular cancer is an established risk factor for adult
      testicular germ cell tumors (GCT). We evaluated the association between family
      history of cancer and pediatric GCT in a Children's Oncology Group case-control
      study that included 274 GCT cases (195 female and 79 male) diagnosed < age 15
      years and 418 controls frequency matched to cases on sex and age. Family history
      data were collected through telephone interviews with biological mothers and
      fathers and unconditional logistic regression was used to evaluate associations
      with GCT adjusting for potential confounders. A family history of cancer with
      onset < age 40 years was associated with a reduced risk of GCT among female cases
      (Odds Ratio (OR) = 0.50, 95% Confidence Interval (CI) 0.28-0.89) and an increased
      risk among male cases (OR = 2.56, 95% CI 1.02-6.44). Male cases were more likely
      to report family history of melanoma compared with male controls (OR = 4.65, 95%
      CI 1.40-15.4). There was an inverse association between family history of ovarian
      or uterine cancers and GCT in girls (OR = 0.46, 95% CI 0.22-0.96). These sex and
      cancer site specific associations should be confirmed in additional studies as
      they may provide clues to the etiology of pediatric GCT.

PMID- 19842051
TI  - trans-Fatty acid consumption and its association with distal colorectal cancer in
      the North Carolina Colon Cancer Study II.
AB  - Recently, the potential health effects of trans-fatty acid consumption have
      raised concerns. A few studies have examined the risk of colorectal cancer with
      increasing consumption of trans-fatty acids, but none investigated the risk of
      rectal cancer, which may have different risk factors than colon cancer. Our
      objective was to explore the relationship between trans-fatty acid consumption
      and distal colorectal (sigmoid, rectosigmoid, and rectal) cancer using a case
      control study of Whites (n = 1,516) and African Americans (n = 392) in North
      Carolina from 2001 to 2006. Matched cases and controls were interviewed about
      demographic information, lifestyle factors, and diet. White cases reported higher
      mean consumption of trans-fatty acid than White controls, but mean consumption
      was similar for African American cases and controls. Relative to the lowest
      quartile, the highest quartiles of energy-adjusted trans-fatty acid consumption
      were positively associated with distal colorectal cancer for Whites [adjusted ORs
      for the third and fourth quartiles are 1.54 (95%CI: 1.12, 2.13) and 1.45 (95%CI:
      1.04, 2.03), respectively]. Consumption was not associated with distal colorectal
      cancer in African Americans [adjusted ORs for the third and fourth quartiles are
      0.98 (95%CI: 0.47, 2.05) and 0.87 (95%CI 0.42, 1.81), respectively]. In
      conclusion, high consumption of trans-fatty acids was positively associated with
      distal colorectal cancer among Whites.

PMID- 19842052
TI  - Sequence map of the 3-Mb Giardia duodenalis assemblage A chromosome.
AB  - The genome of the gut protozoan parasite Giardia duodenalis (assemblage A) has
      been sequenced and compiled as contigs and scaffolds (GiardiaDB-
      http://GiardiaDB.org ), but specific chromosome location of all scaffolds is
      unknown. To determine which scaffolds belong to the 3-Mb chromosome, a library of
      probes specific for this chromosome was constructed. The probes were hybridised
      to NotI-cleaved whole chromosomes, and the combined size of different NotI
      segments identified by the probes was 2,225 kb indicating the probes were well
      distributed along the 3-Mb chromosome. Six scaffolds (CH991814, CH991779,
      CH991793, CH991763, CH991764, and CH991761) were identified as belonging to the 3
      Mb chromosome, and these scaffolds were ordered and oriented according to
      scaffold features including I-PpoI sites and hybridisation pattern. However, the
      combined size of scaffolds was more than 4 Mb. Approximately, 1 Mb of scaffold
      CH991763 carrying previously identified sequences specific for the 1.5-Mb
      chromosome(s) including subtelomeric sequence was reassigned, and several other
      anomalies were addressed such that the final size of the apparently 3-Mb
      chromosome is estimated to be 2,885 kb. This work addresses erroneous computer
      based assignment of a number of contigs and emphasises the need for alternative
      and confirmatory methods of scaffold construction.

PMID- 19842053
TI  - Indirect co-culture with tenocytes promotes proliferation and mRNA expression of
      tendon/ligament related genes in rat bone marrow mesenchymal stem cells.
AB  - Recent evidences have suggested that humoral factors released from the
      appropriate co-cultured cells influenced the expansion and differentiation of
      mesenchymal stem cells (MSCs). However, little is known about the proliferation
      and differentiation of MSCs subjected to co-culture condition with tenocytes. In
      this study, we aimed to establish a co-culture system of MSCs and tenocytes and
      investigate the proliferation and tendon/ligament related gene expression of
      MSCs. MTT assay was used to detect the expansion of MSCs. Semi-quantitative RT
      PCR was performed to investigate the expression of proliferation associated c-fos
      gene and tendon/ligament related genes, including type I collagen (Col I), type
      III collagen (Col III), tenascin C and scleraxis. Significant increase in MSCs
      expansion was observed after 3 days of co-culture with tenocytes. The c-fos gene
      expression was found distinctly higher than for control group on day 4 and day 7
      of co-culture. The mRNA expression of four tendon/ligament related genes was
      significantly up-regulated after 14 days of co-culture with tenocytes. Thus, our
      research indicates that indirect co-culture with tenocytes promotes the
      proliferation and mRNA expression of tendon/ligament related genes in MSCs, which
      suggests a directed differentiation of MSCs into tendon/ligament.

PMID- 19842054
TI  - Study of kinetic parameters for the production of recombinant rabies virus
      glycoprotein.
AB  - Gene expression in insect cells is an advantageous system for recombinant protein
      production, mainly because of its capacity to produce complex proteins with
      correct post-translational modifications. Recently, we identified and purified a
      protein from Lonomia obliqua hemolymph able to increase the production of rabies
      virus glycoprotein, expressed in Drosophila melanogaster cells, by about 60%. In
      this work, the kinetic parameters for cell growth and recombinant rabies virus
      glycoprotein production were determined in cultures of transfected Drosophila
      melanogaster Schneider 2 (S2) cells expressing recombinant rabies virus
      glycoprotein (rRVGP), enriched and non-enriched with the hemolymph of Lonomia
      obliqua (Hb). The highest concentration of rRVGP was achieved at the beginning of
      the culture enriched with Hb, indicating that the cells produce greater amounts
      of rRVGP per cell (specific rRVGP concentration) at the early exponential growth
      phase. After day 8, a decrease in the concentration of rRVGP (ng/mL) was
      observed, probably due to protein decomposition. The average specific rRVGP
      production rate (mu(rRVGP)) was 30 ng rRVGP/10(7)cell.day, higher than that
      observed in the non-enriched culture.

PMID- 19842055
TI  - A survey to establish performance standards for the production of transgenic
      mice.
AB  - The generation of transgenic mice by microinjection of DNA into the pronuclei of
      fertilized oocytes was described in the early 1980s. A number of parameters
      affecting the efficiency of the technique were soon identified, including the
      type of DNA construct, the concentration of DNA being injected, and, most
      importantly, the strain of mice used for oocyte donors. Since then, hundreds of
      laboratories and transgenic core facilities across the world have successfully
      used this technique, essentially as originally described, to create thousands of
      new transgenic mouse lines. However, the overall procedure continues to be
      relatively inefficient, in terms of the number of fertilized oocytes required to
      produce a transgenic mouse, and variations in yields from day to day and
      construct to construct can be large. Consequently, core facilities often struggle
      to explain to their customers why a sufficient number of transgenic founders were
      not produced from a given construct. We believe the field (and individual
      facilities) would benefit from a rigorous assessment of average yields and
      expected variations in yields. To this end, we have initiated a survey from the
      International Society for Transgenic Technologies (ISTT) web site (
      www.transtechsociety.org ), to obtain raw microinjection data from as many
      facilities as possible. We intend to use this data to establish performance
      standards for the field. Existing facilities will be able to refer to these
      standards in dealing with dissatisfied clients, and new facilities will be able
      to aim for an achievable goal. We may even be able to discover an optimum
      combination of factors that will allow every facility to achieve higher yields.

PMID- 19842056
TI  - Phosphonate metabolism in Helicobacter pylori.
AB  - Helicobacter pylori has been shown to degrade two phosphonates, N-phosphonoacetyl
      L: -aspartate and phosphonoacetate; however, the bacterium does not have any
      genes homologous to those of the known phosphonate metabolism pathways suggesting
      that H. pylori may have a novel phosphonate metabolism pathway. Growth of H.
      pylori on phosphonates was studied and the catabolism of these compounds was
      measured employing (1)H-nuclear magnetic resonance spectroscopy. The specificity
      of the catabolic enzymes was elucidated by assaying the degradation of several
      phosphonates and through substrate competition studies. H. pylori was able to
      utilise phenylphosphonate as a sole source of phosphate for growth. Three strains
      of H. pylori showed sigmoidal enzyme kinetics of phenylphosphonate catabolism.
      Allosteric kinetics were removed when lysates were fractionated into cytosolic
      and membrane fractions. Catabolic rates increased with the addition of DTT,
      Mg(2+) and phosphate and decreased with the addition of EDTA. The physiological
      properties of H. pylori phosphonate metabolism were characterised and the
      presence of at least two novel phosphonate catabolism pathways that do not
      require phosphate starvation growth conditions for activity has been established.

PMID- 19842057
TI  - Mitral annulus staining during left ventriculography.

PMID- 19842058
TI  - Identification of HSP27 as a potential tumor marker for colorectal cancer by the
      two-dimensional polyacrylamide gel electrophoresis.
AB  - The identification of specific biomarkers for colorectal cancer would provide the
      basis for early diagnosis, prognosis, therapy, as well as clues for understanding
      the molecular mechanisms governing cancer progression. This study was designed to
      use comparative proteomics technology to find the differentially expressed
      proteins between human colorectal carcinoma and the corresponding normal tumor
      adjacent colorectal tissues. We have used the highly sensitive two-dimensional
      gel electrophoresis (2-DE) coupled with matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) for the
      identification of proteins differentially expressed in tumoral and neighboring
      normal mucosa. We have detected differences in abundance of 42 proteins with
      statistical variance of the tumor versus normal spot volume ratio within the 95th
      confidence level (Student's t-test; P < 0.05). 10 out of 42 analyzed proteins
      were unambiguously identified by MS coupled with database interrogation as being
      differentially expressed in colorectal cancer. Of the 10 newly implicated
      proteins, HSP27 was chosen for detailed analysis. Preliminary studies
      demonstrated that the differentially expressed proteins found by 2-DE could be
      confirmed and validated by western blotting and immunohistochemistry analyses in
      those few cases. The results suggest that HSP27 might be a potential biomarker
      for early diagnosis, prognosis, monitoring in the therapy of colorectal
      carcinoma.

PMID- 19842059
TI  - An examination of aspartate decarboxylase and glutamate decarboxylase activity in
      mosquitoes.
AB  - A major pathway of beta-alanine synthesis in insects is through the alpha
      decarboxylation of aspartate, but the enzyme involved in the decarboxylation of
      aspartate has not been clearly defined in mosquitoes and characterized in any
      insect species. In this study, we expressed two putative mosquito glutamate
      decarboxylase-like enzymes of mosquitoes and critically analyzed their substrate
      specificity and biochemical properties. Our results provide clear biochemical
      evidence establishing that one of them is an aspartate decarboxylase and the
      other is a glutamate decarboxylase. The mosquito aspartate decarboxylase
      functions exclusively on the production of beta-alanine with no activity with
      glutamate. Likewise the mosquito glutamate decarboxylase is highly specific to
      glutamate with essentially no activity with aspartate. Although insect aspartate
      decarboxylase shares high sequence identity with glutamate decarboxylase, we are
      able to closely predict aspartate decarboxylase from glutamate decarboxylase
      based on the difference of their active site residues.

PMID- 19842060
TI  - p53 Promotes proteasome-dependent degradation of oncogenic protein HBx by
      transcription of MDM2.
AB  - Hepatitis B virus X protein (HBx) is closely involved in the development of
      hepatocellular carcinoma (HCC). Tumor suppressor p53 was reported to induce HBx
      degradation and repress its oncogenic function recently, but the molecular
      mechanism is unknown. In this study, we attempted to identify the underlying
      mechanism. We found that overexpression of p53 protein reduces the level of HBx
      protein and shortens its half-life, however, in MDM2 knock out cells, p53 has no
      effects on degradation of HBx, meanwhile, overexpression of MDM2 in absence of
      p53 can accelerate turnover of HBx protein. These indicate that p53-mediated HBx
      degradation is MDM2-dependent. MDM2 interacts with HBx in vitro and in vivo but
      does not promote its ubiquitination. In consistent with the results above, HCC
      tissue samples with wild-type p53 hardly detect HBx protein, whereas, HBx always
      accumulate in the tissues with mutant p53. Our data provide a possible mechanism
      on how p53 regulate HBx stability and also a new clue for the study of p53
      mutation and HCC development.

PMID- 19842061
TI  - Analysis of Toxoplasma gondii surface antigen 2 gene (SAG2). Relevance of
      genotype I in clinical toxoplasmosis.
AB  - Toxoplasma gondii is one of the most successful protozoan parasites given its
      ability to manipulate the immune system and establish a chronic infection. It is
      a parasite with a significant impact on human health, mainly in immunocompromised
      patients. In Europe and North America, only a few clonal genotypes (I, II and
      III) seem to be responsible for the vast majority of Toxoplasma infections.
      Surface antigen 2 gene (SAG2) has been extensively used for genotyping T. gondii
      isolates. The analysis of this locus reveals that in Northern hemisphere, human
      disease causing isolates are mainly type II, whereas T. gondii isolated from
      different animals are both type II and III. Since the immune response depends on
      parasite genotype, it seems relevant to characterize parasites producing human
      toxoplasmosis in different geographical areas. The growing information about the
      prevalent T. gondii genotypes in South America mostly refers to domestic animals.
      This is the first report of genetic characterization of T. gondii isolates from
      clinical samples in Chile, South America. All the samples analyzed corresponded
      to SAG2 type I isolates, and they differ from classic SAG2 type I by genetic
      polymorphisms. This study contributes to the scarce available information on T.
      gondii at South America, and reinforces an emerging concept suggesting that SAG2
      type I, rather than II, parasites are a frequent cause of clinical toxoplasmosis
      in this continent.

PMID- 19842062
TI  - Characterization of unique heavy chain fibroin filaments spun underwater by the
      caddisfly Stenopsyche marmorata (Trichoptera; Stenopsychidae).
AB  - The silks of both Lepidoptera and its sister order Trichoptera contain a
      homologue of heavy chain (H-fibroin), which is assumed to determine the physical
      properties of the fiber, such as elasticity and toughness. The long repetitive
      region of the H-fibroin caddisfly Stenopsyche marmorata shows a conspicuous
      hierarchical structure that is composed of huge units, which are mainly
      constructed from four large blocks (SA, SB, SC and SD) arranged in an orderly
      fashion. Each block contains short, distinct motifs such as SXSXSX(SX), GPXG(X)(1
      3) or triplet GGX, which also occur in lepidopteran and spider filaments. The SA,
      SB and SC blocks have nearly fixed amino acid numbers, while the length of the SD
      block varies, usually due to a variable number of GPXGXXX repeats. The multiple
      sandwich structure that occurs in the SB block is assumed to be unique to the
      caddisfly and may be related to the use of silk in an aqueous environment. The
      overall average of hydrophilicity in the repetitive H-fibroin region of S.
      marmorata is -0.609, whereas hydrophobicity prevails in most lepidopteran H
      fibroins. Gly (29.51%), Pro (11.28%) and Ser (10.90%) are the three predominant
      amino acids of H-fibroin, and the high content of essential amino acids reflects
      the energy-rich food resources of the caddisfly. The H-fibroin of S. marmorata is
      about 400-500 kDa and expressed in both the middle and posterior silk glands,
      which is different from the expression pattern in Lepidoptera species.

PMID- 19842063
TI  - Predictive genetic testing in children: where are we now? An overview and a UK
      perspective.

PMID- 19842064
TI  - NMR assignments of the intrinsically disordered  K2 and YSK2 dehydrins.
AB  - Dehydrins are proteins expressed by plants during various dehydrative stresses
      (drought, cold, and high salinity) to reduce cellular damage. These intrinsically
      disordered proteins are thought to function by binding to proteins to prevent
      denaturation, and to membranes to prevent leakage. Here, we report the 1H, 15N,
      and 13C chemical shift assignments of the K2 and YSK2 dehydrins from Vitis
      riparia (wild grape). Our results show that the segmental nature of dehydrins
      allows for the assignments of the shorter dehydrins to be used in that of the
      longer forms.

PMID- 19842065
TI  - Mechanotransduction by TRP channels: general concepts and specific role in the
      vasculature.
AB  - Transient receptor potential (TRP) ion channel superfamily is involved in sensing
      and transmission of a broad variety of external or internal stimuli, including
      but not limited to mechanical stress. Based on homology analysis, genetic and
      molecular studies have recently identified TRP channels in different tissues,
      comprising blood vessels. In invertebrates, many TRP channels including five TRPV
      channels identified in Caenorhabditis elegans and two in Drosophila have been
      implicated in mechanosensory behaviors as molecular basis of volume regulation,
      hearing and touch sensitivity. Consistently, in mammals many TRP family members
      such as TRPC1, TRPC3, TRPC6, TRPM4, TRPM7, TRPN1, TRPA1, TRPY1, TRPP1, TRPP2, and
      notably, TRPV1, TPRV2 as well as TRPV4 have been reported to be involved in
      mechanotransduction. This review summarizes recent and at times controversial
      findings on the role and regulation of TRP channels in mechanotransduction.
      Specifically, we highlight the relevance of TRPV channels in vascular regulation
      and focus on TRPV4 in the vascular system of the lung, which is constantly
      exposed to a unique combination of circumferential and longitudinal strains. In
      light of our observation in intact pulmonary microvessels that mechanical stress
      induced Ca(2+) signaling in endothelial cells is closely related to TRPV4
      activity, we postulate that TRPV4 plays a critical role in lung vascular
      mechanotransduction. The progress in this rapidly expanding field may allow for
      the identification of new molecular targets and the development of new
      therapeutic approaches in a number of intractable diseases related to mechanical
      stress.

PMID- 19842066
TI  - Bioactive secondary metabolites from a new terrestrial Streptomyces sp. TN262.
AB  - During our search for Streptomyces spp. as new producers of bioactive secondary
      metabolites, the ethyl acetate extract of the new terrestrial Streptomyces
      isolate TN262 delivered eight antimicrobially active compounds. They were
      identified as 1-acetyl-beta-carboline (1), tryptophol (2), cineromycin B (3), 2,3
      dihydrocineromycin B (4), cyclo-(tyrosylprolyl) (5), 3-(hydroxyacetyl)-indole
      (6), brevianamide F (7), and cis-cyclo-(L-prolyl-L-leucyl) (8). Three further
      metabolites were detected in the unpolar fractions using GC-MS and tentatively
      assigned as benzophenone (9), N-butyl-benzenesulfonamide (10), and hexanedioic
      acid-bis-(2-ethylhexyl) ester (11). This last compound is known as plasticizer
      derivatives, but it has never been described from natural sources. In this
      article, we describe the identification of the new Streptomyces sp. isolate TN262
      using its cultural characteristics, the nucleotide sequence of the corresponding
      16S rRNA gene and the phylogenetic analysis, followed by optimization, large
      scale fermentation, isolation of the bioactive constituents, and determination of
      their structures. The biological activity of compounds (2), (3), (4), and those
      of the unpolar fractions was addressed as well.

PMID- 19842067
TI  - Production and characterization of a novel laccase with cold adaptation and high
      thermal stability from an isolated fungus.
AB  - A new white-rot fungus SYBC-L1, which could produce an extracellular laccase, was
      isolated from a decayed Elaeocarpus sylvestris. The strain was identified as
      Pycnoporus sp. SYBC-L1 according to the morphological characteristics and
      ribosomal ITS1-5.8S-ITS2 RNA genomic sequence analysis. The highest laccase
      activity of 24.1 U ml(-1), which was approximately 40-fold than that in basal
      medium, was achieved in optimal culture medium in submerged fermentation. The
      laccase produced by Pycnoporus sp. SYBC-L1 was not only a cold adaptation enzyme
      with a relative catalytic activity of 30.2% at 0 degrees C but also a high
      thermostable enzyme. The half-lives at 60, 70 and 80 degrees C were 85.5, 37.2,
      and 2.6 h, respectively. The laccase could effectively decolorize weak acid blue
      AS and diamond black PV up to 88% and 74.7%, respectively, within 2 h in the
      absence of any redox mediators. The results suggested Pycnoporus sp. SYBC-L1 was
      a potential candidate for laccase production and industrial application.

PMID- 19842068
TI  - Fibrinolytic serine protease isolation from Bacillus amyloliquefaciens An6 grown
      on Mirabilis jalapa tuber powders.
AB  - In this study, Mirabilis jalapa tuber powder (MJTP) was used as a new complex
      organic substrate for the growth and production of fibrinolytic enzymes by a
      newly isolated Bacillus amyloliquefaciens An6. Maximum protease activity (1,057
      U/ml) with casein as a substrate was obtained when the strain was grown in medium
      containing (grams per liter) MJTP 30, yeast extract 6, CaCl(2) 1, K(2)HPO(4) 0.1,
      and K(2)HPO(4) 0.1. The strain was also found to grow and produce extracellular
      proteases in a medium containing only MJTP, indicating that it can obtain its
      carbon, nitrogen, and salts requirements directly from MJTP. The B.
      amyloliquefaciens An6 fibrinase (BAF1) was partially purified, and fibrinolytic
      activity was assayed in a test tube with an artificial fibrin clot. The molecular
      weight of the partially purified BAF1 fibrinolytic protease was estimated to be
      30 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel
      filtration. The optimum temperature and pH for the caseinolytic activity were 60
      degrees C and 9.0, respectively. The enzyme was highly stable from pH 6.0 to 11.0
      and retained 62% of its initial activity after 1 h incubation at 50 degrees C.
      However, the enzyme was inactivated at higher temperatures. The activity of the
      enzyme was totally lost in the presence of phenylmethylsulfonyl fluoride,
      suggesting that BAF1 is a serine protease.

PMID- 19842069
TI  - Role of AP-2alpha transcription factor in the regulation of synapsin II gene
      expression by dopamine D1 and D2 receptors.
AB  - Synapsins are a family of neuron-specific phosphoproteins involved in synaptic
      vesicle docking, synaptogenesis, and synaptic plasticity. Previous studies have
      reported an increase in synapsin II protein by dopaminergic agents in the
      striatum, medial prefrontal cortex, and nucleus accumbens. This study
      investigated the mechanistic pathway involved in synapsin II regulation by
      dopaminergic drugs using primary midbrain neurons to determine which of several
      transcription factors regulates synapsin II expression. Protein kinase A (PKA)
      participation in the signaling pathway was examined using selective PKA
      inhibitors, which reduced synapsin II expression in cell cultures while
      dopaminergic agents were unable to increase synapsin II in the presence of the
      PKA inhibitor. Transcription factor involvement was further investigated using
      separate cultures treated with antisense deoxyoligonucleotides (ADONs) against
      the following transcription factors: activating protein 2 alpha (AP-2alpha),
      early growth response factor 1 (EGR-1), or polyoma enhancer activator-3 (PEA-3).
      Selective knockdown of AP-2alpha by ADONs reduced synapsin II levels, whereas
      treatment with EGR-1 and PEA-3 ADONs did not affect synapsin II expression.
      Furthermore, dopaminergic agents were no longer able to influence synapsin II
      concentrations following AP-2alpha knockdown. Collectively, these results
      indicate that a cyclic adenosine-3',5'-monophosphate/PKA-dependent mechanism
      involving the AP-2alpha transcription factor is likely responsible for the
      increase in neuronal synapsin II following dopamine D1 receptor stimulation or
      dopamine D2 receptor inhibition.

PMID- 19842070
TI  - Autoimmunity and recurrent pregnancy losses.
AB  - The relationship between autoimmunity and reproduction has long been recognized.
      This relationship is bidirectional and includes many diverse issues, but in this
      review article, we focus on which autoimmune disturbances are the basic cause of
      recurrent pregnancy losses in patients with autoimmune diseases. The
      antiphospholipid antibodies seem to be clearly associated with recurrent
      miscarriage. Although there is no agreement on the mechanisms of recurrent
      pregnancy losses in patients with these antibodies, vasculopathy of the terminal
      spiral arteries may be implicated and there is a general consensus to routinely
      screen for antiphospholipid antibodies in patients with recurrent miscarriage.
      Well-designed diagnostic studies are needed to estimate the true association
      between other specific autoantibodies and recurrent miscarriage.

PMID- 19842071
TI  - No association of VEGF polymorphims with Alzheimer's disease.
AB  - The vascular hypothesis of Alzheimer's disease (AD) has brought the vascular
      endothelial growth factor (VEGF) into focus. The genomic region including the
      VEGF gene has been linked to AD and single nucleotide polymorphisms (SNPs) of the
      VEGF have in previous studies been associated with AD risk. To further evaluate
      these findings, we genotyped two SNPs in the VEGF gene (rs699947 [-2578]) and
      rs1570360 [-1154]) by TaqMan Allelic Discrimination in a study sample including
      AD patients (n = 801) and controls (n = 286). In a subgroup of the population
      these SNPs were analyzed in relation to APOE epsilon4 genotype, to cerebrospinal
      fluid biomarkers (T-tau, P-tau, and beta(42)-Amyloid) as well as to
      neuropathological markers for AD (neurofibrillary tangles and senile plaques). No
      significant associations with risk for AD or any of the studied biomarkers could
      be found in this study, thus not supporting VEGF as being a major risk gene for
      AD.

PMID- 19842072
TI  - Arachidonic acid induces acetyl-CoA carboxylase 1 expression via activation of
      CREB1.
AB  - Acetyl-CoA carboxylase (ACC; EC 6.4.1.2) is the major enzyme of fatty acid
      synthesis and oxidation in response to dietary changes. In animals, there are two
      major isoforms of ACCs, ACC1 and ACC2, which are encoded by different genes and
      display distinct tissue and cellular distribution. We examined the effect of high
      concentration of arachidonic acid (AA) on the expression of ACC1 mRNA in HepG2
      hepatoma cells cultured in the absence of insulin. After 12 h of treatment, AA
      was found to significantly up-regulate ACC1 mRNA level as well as that of cAMP
      regulatory element binding protein 1 (CREB1), implying the possible interactions
      between ACC1 and CREB1. In support of the hypothesis, several potential CREB1
      binding sites were identified within the PII promoter of ACC1. Further
      experiments demonstrated that transient over-expression of CREB1 in HepG2 cells
      activates ACC1 PII promoter and induces the production of triacylglycerol in
      response to AA, indicating that the effect of AA on ACC1 is possibly regulated
      via CREB1.

PMID- 19842075
TI  - Predicting VBAC success: from theory to clinical practice.

PMID- 19842073
TI  - DNA methylation: an introduction to the biology and the disease-associated
      changes of a promising biomarker.
AB  - DNA methylation occurring on the 5 position of the pyrimidine ring of cytosines
      in the context of the dinucleotide sequence CpG forms one of the multiple layers
      of epigenetic mechanisms controlling and modulating gene expression through
      chromatin structure. It closely interacts with histone modifications and
      chromatin remodeling complexes to form the genomic chromatin landscape. DNA
      methylation is essential for proper mammalian development, crucial for imprinting
      and plays a role in maintaining genomic stability as well as in dosage
      compensation. DNA methylation patterns are susceptible to change in response to
      environmental stimuli such as diet or toxins, whereby the epigenome seems to be
      most vulnerable during early in utero development. Aberrant DNA methylation
      changes have been detected in several diseases, particularly cancer where genome
      wide hypomethylation coincides with genespecific hypermethylation. DNA
      methylation patterns can be used to detect cancer at very early stages, to
      classify tumors as well as predict and monitor the response to antineoplastic
      treatment. As a stable nucleic-acid-based modification with limited dynamic range
      that is technically easy to handle, DNA methylation is a promising biomarker for
      many applications.

PMID- 19842076
TI  - [Clinical experience with pegaptanib in the treatment of age-related macular
      degeneration (AMD)].
AB  - BACKGROUND: Intravitreal anti-VEGF therapy with pegaptanib has proven to be safe
      and effective for the treatment of neovascular AMD in large clinical studies. We
      report the clinical experience with pegaptanib in an ophthalmology practice in
      Germany. PATIENTS AND METHODS: 27 eyes of 27 patients with neovascular AMD
      underwent treatment with pegaptanib. Ten patients received four injections, 16
      patients received 3 injections and one patient received a single injection of
      pegaptanib. At each visit, visual acuity was measured before and intraocular
      pressure (IOP) both before and after an injection. All patients had a fluorescein
      angiography (FA) at both baseline and final visit. OCT assessment was not
      performed. RESULTS: Intravitreal anti-VEGF therapy was well tolerated, there was
      only one case with a minor ocular complication (a mild form of endophthalmitis).
      89 % of patients in the current series lost fewer than 3 lines over the course of
      24 weeks. 33 % of the patients gained visual acuity. In some cases there was a
      distinct reduction of the activity of the lesion in tFA. CONCLUSIONS:
      Intravitreal therapy with pegaptanib is both safe and effective, it is notable
      that stabilisation of vision occurred although the patients in the present
      analysis tended to have relatively progressed disease at the onset of the
      treatment.

PMID- 19842077
TI  - [Sonographic volumetry of the urinary bladder in paediatric patients. value of
      different calculation formulae taking into account a simple formula that is
      calculable in one's head].
AB  - BACKGROUND: Volumetry of the urinary bladder is a frequently performed
      sonographic procedure. Usually the formula of the prolate ellipsoid is applied
      for this purpose. In the literature however a variety of different formulas is
      proposed. PURPOSE: The aim of this study was to evaluate different simple
      formulae used for the calculation of the bladder volume in children, taking into
      account a formula that is easily calculable in one's head. MATERIAL AND METHODS:
      139 children were examined by sonography, 6 different formulae were applied. The
      bladder volume was confirmed by micturition. Only children without residual
      volume were included in the study. RESULTS: 82 children (mean age: 8.5 years)
      could be included with a mean bladder volume of 92 mL (0 to 227 mL). The mean
      error ranged from 20.2 % (cuboid formula) to 38.0 % (prolate ellipsoid). With
      decreasing bladder volume all formulae showed an increasing error and a tendency
      for underestimation of the bladder volume. For small volumes best results were
      achieved by the cuboid formula with a mean error of 26.4 %. The formula of the
      prolate ellipsoid yielded the worst results. The proposed truncation formula,
      easily calculable in one's head, showed better results than both the formula of
      the prolate ellipsoid and the cuboid formula. CONCLUSION: The formula of the
      prolate ellipsoid should not be used for bladder volumetry in children. Small
      bladder volumes should be calculated by multiplying the three diameters of the
      bladder (cuboid formula). If the calculated volume lies above 60 mL a correction
      factor of 0.8 should be used to avoid overestimation of the true bladder volume.

PMID- 19842078
TI  - [Is there a correlation between S100 beta and post-concussion symptoms after mild
      traumatic brain injury?].
AB  - In the past a lot of patients suffered from post-concussive symptoms (PCS) after
      mild traumatic brain injury (mTBI). The present prospective study (n = 73) was
      intended to help predict the outcome after mTBI with blood asservation for
      analysis of S100 beta 3 hours after trauma. There was no statistically
      significant correlation be-tween PCS or even of single symptoms and elevated
      marker levels. Serum S100 beta appears to be a poor predictor of the outcome
      following mild TBI. Establishing a diagnosis of "PCS" will still be hard in
      future, since no objective diagnostic -method exists. The most important facts
      are a precise examination and a history of the patient with a negative CT scan of
      the head.

PMID- 19842079
TI  - [Spontaneous rupture of a splenic artery].
AB  - BACKGROUND: Hemoperitoneum due to spontaneous rupture of a visceral vessel may
      result from a variety of underlying pathologies. However, its idiopathic form
      does not show evidence of any predisposition. PATIENT AND METHODS: An abdominal
      CT scan for acute abdominal pain yielded the unexpected diagnosis of a ruptured
      splenic artery in a 21-year-old patient. Hemostasis was achieved by endovascular
      coiling of a segmental splenic artery lacking any evidence of pathological
      transformation. An extensive intraabdominal hematoma was evacuated in a
      consecutive laparoscopy which, furthermore, confirmed interventional success.
      Despite extensive diagnostic efforts, the cause of the bleeding remained
      undefined. CONCLUSION: Spontaneous hemoperitoneum may occasionally be considered
      as a cause of acute abdomial pain and is diagnostically challenging. An
      interdisciplinary approach is desirable to meet the objective of modern organ
      preserving therapy in splenic artery rupture.

PMID- 19842087
TI  - Tital page - ultrasound findings in newborns with amiodarone-induced
      hypothyroidism.

PMID- 19842088
TI  - Early onset preeclampsia and second trimester serum markers.
AB  - OBJECTIVE: To examine serum markers measured in the second trimester to identify
      women who subsequently develop preeclampsia. METHODS: Clinically defined
      preeclampsia was confirmed in 45 women who had provided a serum sample as part of
      Down syndrome screening. Preeclampsia was categorized as mild or severe, as well
      as early (<32 weeks) or late onset. Each case was matched with five controls
      based on gestational age and date of serum collection. Stored sera were retrieved
      and tested for inhibin A, soluble vascular endothelial growth factor receptor 1
      (sVEGF R1), placental growth factor (PlGF), and endoglin. Results were converted
      to multiples of the median (MoM) and compared in case and control pregnancies.
      Univariate analysis was used to identify the strongest markers, which were then
      used in a multivariate model. RESULTS: Inhibin A, PlGF, and endoglin were
      consistently associated with preeclampsia, especially for early onset disease. A
      multivariate model using the three markers could identify 50% of the pregnancies
      with early onset preeclampsia with a 2% false positive rate. CONCLUSION: The
      levels of inhibin A, PlGF, and endoglin in the second trimester can be combined
      using a predictive model to provide individualized risk estimates for early onset
      preeclampsia.

PMID- 19842089
TI  - Sampling plans, selective insecticides and sustainability: the case for IPM as
      'informed pest management'.
AB  - Integrated Pest Management (IPM) is considered the central paradigm of insect
      pest management and is often characterized as a comprehensive use of multiple
      control tactics to reduce pest status while minimizing economic and environmental
      costs. As the principal precursor of IPM, the integrated control concept
      formulated the economic theory behind pest management decisions and specified an
      applied methodology for carrying out pest control. Sampling, economic thresholds
      and selective insecticides were three of the critical elements of that
      methodology and are now considered indispensable to the goals of IPM. We examine
      each of these elements in the context of contemporaneous information as well as
      accumulated experience and knowledge required for their skillful implementation
      in an IPM program. We conclude that while IPM is principally about integrating
      control tactics into an effective and sustainable approach to pest control, this
      overarching goal can only be achieved through well-trained practitioners,
      knowledgeable of the tenets conceived in the integrated control concept that
      ultimately yield informed pest management.

PMID- 19842090
TI  - IPM for fresh-market lettuce production in the desert southwest: the produce
      paradox.
AB  - In the 'Integrated Control Concept', Stern et al. emphasized that, although
      insecticides are necessary for agricultural production, they should only be used
      as a last resort and as a complement to biological control. They argued that
      selective insecticide use should only be attempted after it has been determined
      that insect control with naturally occurring biotic agents is not capable of
      preventing economic damage. However, they concluded their seminal paper by
      emphasizing that integrated control will not work where natural enemies are
      inadequate or where economic thresholds are too low to rely on biological
      control. Thus, it is no surprise that insect control in high-value, fresh-market
      lettuce crops grown in the desert southwest have relied almost exclusively on
      insecticides to control a complex of mobile, polyphagous pests. Because lettuce
      and leafy greens are short-season annual crops with little or no tolerance for
      insect damage or contamination, biological control is generally considered
      unacceptable. High expectations from consumers for aesthetically appealing
      produce free of pesticide residues further forces vegetable growers to use
      chemical control tactics that are not only effective but safe. Consequently,
      scientists have been developing integrated pest management (IPM) programs for
      lettuce that are aimed at reducing the economic, occupational and dietary risks
      associated with chemical controls of the past. Most of these programs have drawn
      upon the integrated control concept and promote the importance of understanding
      the agroecosystem, and the need to sample for pest status and use action
      thresholds for cost-effective insect control. More recently, pest management
      programs have implemented newly developed, reduced-risk chemistries that are
      selectively efficacious against key pests. This paper discusses the influence
      that the integrated control concept, relative to zero-tolerance market standards
      and other constraints, has had on the adoption of pest management in desert
      lettuce crops.

PMID- 19842091
TI  - Fitting spending functions.
AB  - Group sequential monitoring is used to provide guidance on stopping a clinical
      trial in progress based on interim evaluation of its efficacy objectives. A trial
      could stop because an experimental regimen (1) is efficacious, (2) lacks any sign
      of efficacy, or (3) is specifically less efficacious than a control. Group
      sequential methods using alpha- and beta-spending functions (Biometrika 1983;
      70:659-663) are often used to create stopping boundaries for test statistics for
      efficacy hypotheses computed at interim analyses. This paper explores fitting
      alpha- and beta-spending functions that have specific values at specific interim
      analyses. Commonly used one-parameter families may not provide an adequate fit to
      more than one desired critical value. We define new one- and two-parameter
      families to provide additional flexibility along with examples to demonstrate
      their usefulness. The logistic family is one of these two-parameter families,
      which has been applied in several trials.

PMID- 19842092
TI  - Health expenditure and income in the United States.
AB  - This paper investigates the long-run economic relationship between health care
      expenditure and income in the US at a State level. Using a panel of 49 US States
      over the period 1980-2004, we study the non-stationarity and co-integration
      between health spending and income, ultimately measuring income elasticity of
      health care. The tests we adopt allow us to explicitly control for cross-section
      dependence and unobserved heterogeneity. Specifically, in our regression
      equations we assume that the error has a multifactor structure, which may capture
      global shocks and local spill overs in health expenditure. Our results suggest
      that health care is a necessity rather than a luxury, with an elasticity much
      smaller than that estimated in other US studies. Further, we detect significant
      spatial concentration in US health spending. Our broad perspective of cross
      section dependence as well as the methods used to capture it give new insights on
      the debate over the relationship between health spending and income.

PMID- 19842093
TI  - Commentary on 'Case series of liver failure associated with rosiglitazone and
      pioglitazone' by James Floyd et al.

PMID- 19842094
TI  - Ceramide induces endothelial cell senescence.
AB  - Ceramide has been proposed to be a mediator of replicative senescence. Our aim
      was to determine whether ceramide induces senescence in vascular endothelial
      cells. Human umbilical vein endothelial cells were cultured to different
      population doubling levels and ceramide levels were quantitated. The endogenous
      levels of ceramide increased 2.4-fold with senescence onset. Low passage cells
      were chronically treated with exogenous C(6)-ceramide. This treatment induced a
      senescent phenotype as measured by an inhibition of cell proliferation and DNA
      replication while increasing senescence-associated beta-galactosidase expression.
      This is the second cell type in which ceramide induces senescence, thus
      implicating ceramide as a general mediator of cellular senescence.

PMID- 19842095
TI  - Cultured human keratinocytes for optical transmission measurement.
AB  - The challenges of measuring optical properties of human tissues include the
      thickness of the sample, homogenization, or crystallization from freezing of the
      tissue. This investigation demonstrates a method to avoid these problems by
      growing optically thin samples of human keratinocytes as a substitute for ex vivo
      epidermis samples. Several methods of growth were investigated. Resulting samples
      were measured on a spectrophotometer for transmission between 300 nm and 2600 nm.
      The efficacy of the cell growth was confirmed with histological examination of
      several cultured keratinocyte samples. Limitations were the requirement to
      measure samples immediately after removal from the incubation environment, and
      the absence of the irregular structures of normal skin such as hair and glands.

PMID- 19842096
TI  - Role of beta3-adrenoceptors for intrahepatic resistance and portal hypertension
      in liver cirrhosis.
AB  - Increased intrahepatic resistance and splanchnic blood flow cause portal
      hypertension in liver cirrhosis. Nonselective beta-adrenoceptor (beta-AR)
      antagonists have beneficial effects on hyperdynamic circulation and are in
      clinical use. In this context, the role of the beta(3)-AR is undefined. Here we
      investigated their expression and role in portal hypertension in patients and
      rats with liver cirrhosis. We analyzed cirrhotic human and rat tissues (liver,
      splanchnic vessels) and primary rat cells. Protein expression of beta(3)-AR was
      determined by western blot and messenger RNA (mRNA) levels by reverse
      transcription polymerase chain reaction (RT-PCR). Activities of Rho-kinase and
      the nitric oxide (NO) effector protein kinase G (PKG) were assessed by way of
      substrate phosphorylation (moesin, vasodilator-stimulated phosphoprotein [VASP]).
      Cyclic 3',5' adenosine monophosphate (cAMP) accumulation was determined by an
      enzyme-immunoassay kit. The effects of selective beta(3)-AR agonists (CGP12177A,
      BRL37344) and antagonist (SR59230A) were investigated by collagen matrix
      contraction of hepatic stellate cells (HSCs), in situ liver perfusions, and in
      vivo hemodynamic parameters in bile duct ligation and carbon tetrachloride
      intoxication in cirrhotic rats. In cirrhosis of humans and rats, beta(3)-AR
      expression is markedly increased in hepatic and in splanchnic tissues.
      Stimulation of beta(3)-AR leads to relaxation of HSCs by way of cAMP
      accumulation, and by inhibition of Rho-kinase activity; any role of NO and its
      effector PKG was not observed. beta(3)-AR agonists decrease intrahepatic
      resistance and portal pressure in cirrhotic rats. CONCLUSION: There is a marked
      hepatic and mesenteric up-regulation of beta(3)-ARs in human cirrhosis and in two
      different animal models of cirrhosis. The beta(3)-AR-agonists should be further
      evaluated for therapy of portal hypertension.

PMID- 19842097
TI  - Commentary on 'Measurement in clinical trials: a neglected issue for
      statisticians?'.

PMID- 19842098
TI  - Commentary on 'Measurement in clinical trials: a neglected issue for
      statisticians?'.

PMID- 19842099
TI  - Commentary on 'Measurement in clinical trials: a neglected issue for
      statisticians?'.

PMID- 19842100
TI  - Commentary on 'Measurement in clinical trials: a neglected issue for
      statisticians?'.

PMID- 19842101
TI  - Commentary on 'Measurement in clinical trials: a neglected issue for
      statisticians?'.

PMID- 19842104
TI  - Anti-obese property of fucoxanthin is partly mediated by altering lipid
      regulating enzymes and uncoupling proteins of visceral adipose tissue in mice.
AB  - This study investigated the anti-obesity effects of fucoxanthin in diet-induced
      obesity mice fed a high-fat diet (20% fat, wt/wt). The mice were supplemented
      with two doses of fucoxanthin (0.05 and 0.2%, wt/wt) for 6 wk. Fucoxanthin
      significantly lowered body weight and visceral fat-pads weights compared with the
      control group without altering food intake. In epididymal adipose tissue of
      fucoxanthin-fed mice, adipocyte sizes and mRNA expression of lipogenic and fatty
      acid beta-oxidation enzymes were significantly altered in a dose-dependent
      manner. Plasma leptin level was significantly lower in the fucoxanthin groups
      than in the control group, while the adiponectin level was elevated. Fucoxanthin
      significantly down-regulated various lipogenic enzyme activities in epididymal
      adipose tissue with a simultaneous decrease in fatty acid beta-oxidation
      activity. The 0.2% fucoxanthin supplement led to increase mRNA expression of
      uncoupling protein-1 (UCP-1) and UCP-3 in brown adipose tissue and that of UCP-2
      in the epididymal white adipose tissue. However, the 0.05% fucoxanthin only
      elevated UCP-1 mRNA expression in epididymal white adipose tissue. These results
      suggest that the anti-obesity effect of fucoxanthin could be mediated by altering
      lipid-regulating enzymes and UCPs in the visceral fat tissues and plasma
      adipokine levels.

PMID- 19842103
TI  - Anticancer actions of natural and synthetic vitamin E forms: RRR-alpha-tocopherol
      blocks the anticancer actions of gamma-tocopherol.
AB  - Two naturally occurring dietary sources of vitamin E (i.e. RRR-alpha-tocopherol
      (alphaT) and RRR-gamma-tocopherol (gammaT)), the manufactured synthetic form of
      vitamin E, all-racemic-alpha-tocopherol (all-rac-alphaT), as well as a potent
      antitumor analog of vitamin E, RRR-alpha-tocopherol ether-linked acetic acid
      analog (alpha-TEA), were assessed for anticancer actions. Data showed that
      gammaT, all-rac-alphaT, and alpha-TEA but not alphaT or alphaT+gammaT
      significantly inhibited tumor burden of human MDA-MB-231 cells in nude mice.
      Immunohistochemical analyses of tumor tissue showed that all-rac-alphaT and alpha
      TEA increased apoptosis and decreased proliferation in tumor cells while gammaT
      was associated with increased tumor cell apoptosis only. In vitro data showed
      alpha-TEA and gammaT but not all-rac-alphaT or alphaT to inhibit colony formation
      and induce apoptosis. Anticancer actions of alpha-TEA and gammaT involved death
      receptor 5 protein upregulation, Survivin protein downregulation and poly (ADP
      ribose) polymerase cleavage, all of which were blocked by co-treatment with
      alphaT. In summary, both gammaT and alpha-TEA exhibited promising anticancer
      properties in vivo and in vitro, whereas all-rac-alphaT exhibited promising
      anticancer properties in vivo only. Importantly, alphaT not only failed to
      exhibit anticancer properties but it also reduced anticancer actions of gammaT in
      vivo and gammaT and alpha-TEA in vitro.

PMID- 19842105
TI  - Role of dietary patterns for dioxin and PCB exposure.
AB  - Dietary patterns were related to intake and blood concentrations of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs), dioxin-like
      polychlorinated biphenyls (dl-PCBs) and selected non-dioxin-like-PCBs (ndl-PCBs).
      Intake calculations were based on an extensive food frequency questionnaire and a
      congener-specific database on concentrations in Norwegian foods. The study (2003)
      applied a two-step inclusion strategy recruiting representative (n=73) and high
      consumers (n=111) of seafood and game. Estimated median intakes of sum PCDD/PCDFs
      and dl-PCBs of the representative and high consumers were 0.78 and 1.25 pg toxic
      equivalents (TEQ)/kg bw/day, respectively. Estimated median intakes of ndl-PCBs
      (sum chlorinated biphenyl (CB)-28, 52, 101, 138, 153, 180) were 4.26 and 6.40
      ng/kg bw/day. The median blood concentrations of PCDD/PCDFs/dl-PCBs were 28.7 and
      35.1 pg TEQ/g lipid, and ndl-PCBs (sum of CB-101, 138, 153 and 180) 252 and 299
      ng/g lipid. The Spearman correlations between dietary intake and serum
      concentration were r=0.34 (p=0.017) for dl-compounds and r=0.37 (p<0.001) for ndl
      PCBs. Oily fish was the major source of dl-compounds and ndl-PCBs in high and
      representative consumers. Four dietary patterns were identified by principal
      component analysis. Two were related to high intakes, one dominated by oily fish
      ((Omega-3)), the other by fish liver and seagull eggs ("northern coastal"). Only
      the latter was closely associated with high blood concentrations of dioxins and
      PCBs.

PMID- 19842106
TI  - Expansion of human mesenchymal stromal cells on microcarriers: growth and
      metabolism.
AB  - Adult stem cells, or mesenchymal stromal cells (MSCs), are of great potential for
      cell therapy and tissue-engineering applications. However, for therapeutic use,
      these cells need to be isolated from tissue or a biopsy and efficiently expanded,
      as they cannot be harvested in sufficient quantities from the body. In our
      opinion, efficient expansion of MSCs can be achieved in a microcarrier-based
      cultivation system. This study selected a suitable microcarrier for human bone
      marrow-derived stromal cells (HBMSCs), optimized cell-seeding strategies by
      varying serum concentrations, and optimized dynamic expansion of the HBMSCs in a
      microcarrier-based spinner flask cultivation system by applying various feeding
      regimes. Cytodex 1 microcarriers in combination with a low-serum concentration (0
      5%) in the medium resulted in the highest seeding efficiency for the HBMSCs.
      Subsequently, significant expansion of the HBMSCs on these carriers has been
      observed. The highest number of HBMSCs population doublings (4.8 doublings) was
      obtained by a combination of 50% medium refreshment combined with addition of 30%
      medium containing microcarriers every 3 days. Exponential cell growth was
      observed for at least 9 days after seeding, provided that sufficient nutrients
      (such as glucose) were present, metabolite concentrations (such as ammonia) were
      kept below growth-inhibitory concentrations and adequate surface area was present
      for the cells. After dynamic expansion of the HBMSCs, the cells retained their
      differentiation potential and their cell surface markers, indicating that HBMSCs
      expansion on Cytodex 1 microcarriers did not alter the phenotypic properties of
      the cells.

PMID- 19842107
TI  - Compressed collagen gel: a novel scaffold for human bladder cells.
AB  - Collagen is highly conserved across species and has been used extensively for
      tissue regeneration; however, its mechanical properties are limited. A recent
      advance using plastic compression of collagen gels to achieve much higher
      concentrations significantly increases its mechanical properties at the neo
      tissue level. This controlled, cell-independent process allows the engineering of
      biomimetic scaffolds. We have evaluated plastic compressed collagen scaffolds
      seeded with human bladder smooth muscle cells inside and urothelial cells on the
      gel surface for potential urological applications. Bladder smooth muscle and
      urothelial cells were visualized using scanning electron microscopy, conventional
      histology and immunohistochemistry; cell viability and proliferation were also
      quantified for 14 days in vitro. Both cell types tested proliferated on the
      construct surface, forming dense cell layers after 2 weeks. However, smooth
      muscle cells seeded within the construct, assessed with the Alamar blue assay,
      showed lower proliferation. Cellular distribution within the construct was also
      evaluated, using confocal microscopy. After 14 days of in vitro culture, 30% of
      the smooth muscle cells were found on the construct surface compared to 0% at day
      1. Our results provide some evidence that cell-seeded plastic compressed collagen
      has significant potential for bladder tissue regeneration, as these materials
      allow efficient cell seeding inside the construct as well as cell proliferation.

PMID- 19842108
TI  - Donor-matched comparison of dental pulp stem cells and bone marrow-derived
      mesenchymal stem cells in a rat model.
AB  - Dental pulp stem cells (DPSCs) have drawn much interest for the regeneration of
      mineralized tissues, and several studies have compared DPSCs to bone marrow
      derived mesenchymal stem cells (BMMSCs). However, conflicting results, possibly
      due to donor-associated variability, have been published and the regenerative
      potential of DPSCs is currently unclear. In the present study we have sought to
      address this problem using a donor-matched experimental design to robustly
      compare the biological properties of DPSCs and BMMSCs. All experiments were
      performed using cells isolated from a single adult Sprague-Dawley rat. Our
      results show that DPSCs and BMMSCs had similar morphologies and flow cytometry
      profiles, were capable of forming colonies in vitro and were capable of
      osteogenic, chondrogenic and adipogenic differentiation. However, quantitative
      comparisons revealed that DPSCs had a faster population doubling time and a
      higher percentage of stem/progenitor cells in the population, as determined by
      clonogenic assays. Furthermore, while both cell populations formed mineral in
      vitro, DPSCs had significantly higher alkaline phosphatase activity than BMMSCs
      after 3 weeks in osteogenic medium. These data show several key differences
      between DPSCs and BMMSCs and support the possibility of using DPSCs for
      mineralized tissue regeneration.

PMID- 19842109
TI  - Amplification failure of the amelogenin gene (AMELX) caused by a primer binding
      site mutation.

PMID- 19842111
TI  - Second-harmonic generation from a single core/shell quantum dot.
AB  - Nanoparticles emitting two-photon luminescence are broadly used as photostable
      emitters for nonlinear microscopy. Second-harmonic generation (SHG) as another
      two-photon mechanism offers complementary optical properties but the reported
      sizes of nanoparticles are still large, of a few tens of nanometers. Herein,
      coherent SHG from single core/shell CdTe/CdS nanocrystals with a diameter of 10
      to 15 nm is reported. The nanocrystal excitation spectrum reveals resonances in
      the nonlinear efficiency with an overall maximum at about 970 nm. Polarization
      analysis of the second-harmonic emission confirms the expected zinc blende
      symmetry, and allows extraction of the three-dimensional nanocrystal orientation.
      The small size of these nonlinearly active quantum dots, together with the
      intrinsic coherence and orientation sensitivity of the SHG process, are well
      adapted for ultrafast probing of optical near-fields with high resolution as well
      as for orientation tracking for bioimaging applications.

PMID- 19842110
TI  - Vibration stimulates vocal mucosa-like matrix expression by hydrogel-encapsulated
      fibroblasts.
AB  - The composition and organization of the vocal fold extracellular matrix (ECM)
      provide the viscoelastic mechanical properties that are required to sustain high
      frequency vibration during voice production. Although vocal injury and pathology
      are known to produce alterations in matrix physiology, the mechanisms responsible
      for the development and maintenance of vocal fold ECM are poorly understood. The
      objective of this study was to investigate the effect of physiologically relevant
      vibratory stimulation on ECM gene expression and synthesis by fibroblasts
      encapsulated within hyaluronic acid hydrogels that approximate the viscoelastic
      properties of vocal mucosa. Relative to static controls, samples exposed to
      vibration exhibited significant increases in mRNA expression levels of HA
      synthase 2, decorin, fibromodulin and MMP-1, while collagen and elastin
      expression were relatively unchanged. Expression levels exhibited a temporal
      response, with maximum increases observed after 3 and 5 days of vibratory
      stimulation and significant downregulation observed at 10 days. Quantitative
      assays of matrix accumulation confirmed significant increases in sulphated
      glycosaminoglycans and significant decreases in collagen after 5 and 10 days of
      vibratory culture, relative to static controls. Cellular remodelling and hydrogel
      viscosity were affected by vibratory stimulation and were influenced by varying
      the encapsulated cell density. These results indicate that vibration is a
      critical epigenetic factor regulating vocal fold ECM and suggest that rapid
      restoration of the phonatory microenvironment may provide a basis for reducing
      vocal scarring, restoring native matrix composition and improving vocal quality.

PMID- 19842112
TI  - Site-specific self-assembled liquid-gated ZnO nanowire transistors for sensing
      applications.
AB  - A scalable bottom-up solution-based approach for the site-specific realization of
      ZnO nanowire (ZnO-NW)-based field-effect transistors for sensing applications in
      liquids is reported. The nanowires are grown across predefined electrodes
      patterned by photolithography. Site specificity is attained by the use of
      nanoparticles acting as seeds. Using integrated on-chip microchannels and
      microfabricated gate electrodes, electrochemically gated ZnO-NW network
      transistors functioning in liquids are demonstrated. The optimized devices are
      rendered sensitive to pH through chemical functionalization. The unique
      combination of the sensitivity, site specificity, scalability, and cost
      effectiveness of the technique opens up avenues for the routine realization of
      one-dimensional nanostructure-based chemical and biosensors for analytical and
      diagnostic applications.

PMID- 19842113
TI  - One-dimensional arrangement of gold nanoparticles with tunable interparticle
      distance.

PMID- 19842115
TI  - Human cell culture process capability: a comparison of manual and automated
      production.
AB  - Cell culture is one of the critical bioprocessing steps required to generate
      sufficient human-derived cellular material for most cell-based therapeutic
      applications in regenerative medicine. Automated cell expansion is fundamental to
      the development of scaled, robust and cost effective commercial production
      processes for cell-based therapeutic products. This paper describes the first
      application of process capability analysis to establish and compare the short
      term process capability of manual and automated processes for the in vitro
      expansion of a selected anchorage-dependent cell line. Estimates of the process
      capability indices (Cp, Cpk) have been used to assess the ability of both
      processes to consistently meet the requirements for a selected productivity
      output and to direct process improvement activities. Point estimates of Cp and
      Cpk show that the manual process has poor capability (Cp = 0.55, Cpk = 0.26)
      compared to the automated process (Cp = 1.32, Cpk = 0.25), resulting from excess
      variability. Comparison of point estimates, which shows that Cpk < Cp, indicates
      that the automated process mean was off-centre and that intervention is required
      to adjust the location of the process mean. A process improvement strategy
      involving an adjustment to the automated process settings has demonstrated in
      principle that the process mean can be shifted closer to the centre of the
      specification to achieve an estimated seven-fold improvement in process
      performance. In practice, the 90% confidence bound estimate of Cp (Cp = 0.90)
      indicates that that once the process is centred within the specification, a
      further reduction of process variation is required to attain an automated process
      with the desired minimum capability requirement.

PMID- 19842114
TI  - A tissue-like construct of human bone marrow MSCs composite scaffold support in
      vivo ectopic bone formation.
AB  - Biocompatible and osteoconductive cell-scaffold constructs comprise the first and
      most important step towards successful in vivo bone repair. This study reports on
      a new cell-scaffold construct composed of gelatin-based hydrogel and ceramic
      (CaCO(3)/beta-TCP) particles loaded with human MSCs producing a tissue-like
      construct applied as a transplant for in vivo bone formation. Bone marrow-derived
      human MSCs were cultured in osteogenic induction medium. 5 x 10(5) (P(2)) cells
      were loaded on a mixture of hydrogel microspheres and ceramic particles, cultured
      in a rotating dynamic culture for up to 3 weeks. Both hydrogel microspheres and
      ceramic particles coalesced together to form a tissue-like construct, shown by
      histology to contain elongated spindle-like cells forming the new tissue between
      the individual particles. Cell proliferation and cell viability were confirmed by
      Alamar blue assay and by staining with CFDA, respectively. FACS analysis
      conducted before loading the cells, and after formation of the construct,
      revealed that the profile of cell surface markers remained unchanged throughout
      the dynamic culture. The osteogenic potential of the cells composing the tissue
      like construct was further validated by subcutaneous transplants in athymic nude
      mice. After 8 weeks a substantial amount of new bone formation was observed in
      the cell-construct transplants, whereas no bone formation was observed in
      transplants containing no cells. This new cell construct provides a system for in
      vivo bone transplants. It can be tailored for a specific size and shape as needed
      for various transplant sites and for all aspects of regenerative medicine and
      biomaterial science.

PMID- 19842116
TI  - Effects of mechanical loading on collagen propeptides processing in cartilage
      repair.
AB  - Injured articular cartilage has poor reparative capabilities and if left
      untreated may develop into osteoarthritis. Unsatisfactory results with
      conventional treatment methods have brought as an alternative treatment the
      development of matrix autologous chondrocyte transplants (MACTs). Recent evidence
      proposes that the maintenance of the original phenotype by isolated chondrocytes
      grown in a scaffold transplant is linked to mechanical compression, because
      macromolecules, particularly collagen, of the extracellular matrix have the
      ability to 'self-assemble'. In load-bearing tissues, collagen is abundantly
      present and mechanical properties depend on the collagen fibre architecture.
      Study of the active changes in collagen architecture is the focus of diverse
      fields of research, including developmental biology, biomechanics and tissue
      engineering. In this review, the structural model of collagen assembly is
      presented in order to understand how scaffold geometry plays a critical role in
      collagen propeptide processing and chondrocyte development. When physical forces
      are applied to different cell-based scaffolds, the resulting specific twist of
      the scaffolds might be accompanied by changes in the fibril pattern synthesis of
      the new collagen. The alteration in the scaffolds due to mechanical stress is
      associated with cellular signalling communication and the preservation of N
      terminus procollagen moieties, which would regulate both the collagen synthesis
      and the diameter of the fibre. The structural difference would also affect actin
      stabilization, cytoskeleton remodelling and proteoglycan assembly. These effects
      seemed to be dependent on the magnitude and duration of the physical stress. This
      review will contribute to the understanding of mechanisms for collagen assembly
      in both a natural and an artificial environment.

PMID- 19842117
TI  - Ethnic differences in considerations whether or not to participate in prenatal
      screening for Down syndrome.
AB  - OBJECTIVE: To evaluate ethnic differences in considerations whether or not to
      participate in prenatal screening for Down syndrome and to relate these to
      differences in participation. METHOD: The study population consisted of 270
      pregnant women from Dutch, Turkish and Surinamese (African and South Asian)
      ethnic origin, attending midwifery or obstetrical practices in the Netherlands.
      Women were interviewed after booking for prenatal care. Considerations were
      assessed by one open-ended question and 18 statements that were derived from
      focus group interviews. Actual participation was assessed several months later.
      RESULTS: Women from ethnic minorities were less likely to participate in prenatal
      screening, which could be attributed to differences in age and religious
      identity. They more often reported acceptance of 'what God gives', low risk of
      having a child with Down syndrome and costs of screening as considerations not to
      participate in prenatal screening. They also reported many considerations in
      favour of participation, which did not differ from those of Dutch women but were
      less often consistent with actual participation in screening. CONCLUSIONS: Women
      from ethnic minorities should not be stereotyped as being uninterested in
      prenatal screening, but should be better informed about the consequences of
      prenatal screening and Down syndrome.

PMID- 19842118
TI  - Characterization and quantitation of short-chain fructooligosaccharides and
      inulooligosaccharides in fermented milks by high-performance anion-exchange
      chromatography with pulsed amperometric detection.
AB  - With the increased interest in the possible link between fructooligosaccharides
      (FOS) intake from functional foods and health, the need for reliable data on the
      individual FOS content of those foods has become very important. In this study a
      new high-performance anion-exchange chromatography coupled to pulsed amperometric
      detection (HPAEC-PAD) method is described for the selective determination of
      short-chain FOS and inulooligosaccharides (IOS) present in the investigated
      prebiotic food ingredients. Response factor of PAD was investigated in
      relationship with degree of polymerization and isomers. The developed HPAEC-PAD
      method has been applied to characterize short-chain oligosaccharides of the
      inulin series with DP ranging from DP3 to DP7 and IOS from DP2 to DP7. Their
      quantification in commercial water-soluble fibers of relevant importance as
      prebiotic food ingredient added in fermented milks has been performed. In order
      to evaluate the reliability of the proposed method, results have been compared
      with those obtained by the official enzymatic method. Furthermore, this new HPAEC
      PAD method may contribute to clarify the real importance, prebiotic effectiveness
      and biological role of these carbohydrates.

PMID- 19842119
TI  - Application of pressurized liquid extraction in the analysis of aflatoxins B(1),
      B(2), G(1) and G(2) in nuts.
AB  - Aflatoxins (AFs) B(1), B(2), G(1) and G(2) were extracted from nuts by using
      pressurized liquid extraction (PLE) and the PLE extracts were analyzed using HPLC
      with fluorescence detection using photochemical post-column derivatization
      without further cleanup procedures. Several extraction parameters such as
      temperature (25, 40, 60 and 80 degrees C), pressure (500, 1000, 1500 and 2000
      psi), solvent extraction mixture (acetone, acetonitrile, ethyl acetate and
      methanol), number of cycles (1 and 2), use of dispersing agents and cell size (5
      and 11 mL) were investigated for their effects on the extraction performance. The
      results showed 60 degrees C, 1500 psi, acetonitrile, one cycle and a cell size of
      5 mL as most favorable PLE operating conditions. The proposed analytical method
      provides LODs below the maximum levels established by European Union regulations
      and the recoveries of the four AFs were between 77 and 93% at spiking levels of
      4, 2 and 0.5 microg/kg for AFB(1) and AFG(1) and 1, 0.5 and 0.13 microg/kg for
      AFB(2) and AFG(2). Validation was carried out using certified reference
      materials. PLE has been applied for the first time to the analysis of AFs in nuts
      and offers the possibility for fast simple and accurate quantitative
      determination of studied mycotoxins.

PMID- 19842120
TI  - Modeling the effects of different mobile phase compositions and temperatures on
      the retention of various analytes in HPLC.
AB  - A mathematical model is proposed for representing the combined effects of mobile
      phase solvent composition and temperature on the retention of various analytes in
      HPLC. The applicability of the model in describing the retention of four
      macrolides in aqueous mixtures of methanol and acetonitrile determined at 20-80
      degrees C in various volume fractions of the organic modifiers was shown. The
      mean percentage deviation (MPD) was computed as an accuracy criterion in which
      the overall MPD of four analytes investigated in this work was 3.9+/-1.5% (N=72).
      The proposed model could be reduced to two simpler versions. The first version
      concerning the retention data of analytes in one organic modifier at various
      temperatures produced for the retention description of the above experimental
      system as well as for the retention of three benzodiazepines in aqueous mixtures
      of methanol at 25-40 degrees C an overall MPD of 3.6+/-1.8%. The more reduced
      version of the model for calculating the retention factor of one analyte in a
      given organic modifier at various temperatures produced an overall MPD of 1.7+/
      1.1% for both the experimental systems studied. The accuracy of the proposed
      model is compared with recent models to predict the retention of an analyte with
      respect to solvent component of the mobile phase and the temperature of column in
      which the results were comparable. The main advantage of the proposed model is
      its capability to predict the retention of various analytes considering (i)
      temperature of the column, (ii) the mobile phase solvent composition, (iii) the
      chemical structure of the analytes and (iv) the nature of organic modifier.

PMID- 19842121
TI  - Rapid analysis of constituents of Radix Cyathulae using hydrophilic interaction
      reverse phase LC-MS.
AB  - A hydrophilic interaction chromatography (HILIC) and reverse-phase liquid
      chromatography (RPLC) coupled with electrospray TOF MS method was developed for
      the analysis and characterization of constituents in the radix of Cyathula
      officinalis Kuan. Separation parameters of HILIC such as buffer pH, mobile phase
      strength, and organic modifier were evaluated. Fructose, glucose, and sucrose
      were identified by HILIC-ESI/TOF MS. Reverse-phase liquid chromatography-ESI/TOF
      MS were applied for quick and sensitive identification of major saponins in
      Cyathula officinalis. In-source collision-induced dissociation has been performed
      to elucidate the fragmentation pathways of oleanane-, hederagenin-, and gypsogmin
      type saponins. Twelve saponins were characterized in this plant for the first
      time, and four of them were presumed to be new compounds. In addition, one
      phytoecdysteroid (cyasterone) and one coumarin (6,7-dimethoxycoumarin) were
      detected at the same time. The present method was capable of rapid characterizing
      and providing structure information of constituents from herbal drugs.

PMID- 19842122
TI  - GC separation of amino acid enantiomers via derivatization with heptafluorobutyl
      chloroformate and Chirasil-L-Val column.
AB  - Heptafluorobutyl chloroformate (HFBCF), a recently introduced derivatization
      reagent, was examined in enantioseparation of amino acids (AAs) by GC. Twenty
      proteinogenic AAs, plus ornithine, cystine and 4-fluorophenylalanine (internal
      standard) were treated with the reagent and separation properties of the
      derivatives were assessed on a Chirasil-Val capillary column. Nineteen AA
      enantiomers were efficiently separated in 43 min except proline, arginine and
      cystine. The HFBCF derivatives of the studied DL-AAs show improved separation
      over other chloroformate-based derivatives hitherto reported. A combination of
      the improved and faster separation with a simple derivatization protocol,
      involving an immediate one-step reaction-extraction in two-phase aqueous-organic
      medium, and low elution temperatures extend application of HFBCF to chiral AA
      analysis.

PMID- 19842123
TI  - LC method for the analysis of kanamycin residue in swine tissues using
      derivatization with 9-fluorenylmethyl chloroformate.
AB  - A sensitive and robust HPLC method was developed for the determination of
      kanamycin (Kan) in swine tissues. Kan was extracted from tissue with 10% TCA
      (w/v) solution and cleaned up with MCX SPE column. The purified extract was
      derivatized with 9-fluorenylmethyl chloroformate, and then separated on a C18
      column and detected by a fluorescence detector. The linear range of the
      calibration curve was 0.025-1 microg/mL with R(2) of 0.9998. The limits of
      quantification were determined to be 0.1 mg/kg in muscle, 0.2 mg/kg in liver, and
      0.6 mg/kg in kidney, and the average recoveries of Kan from swine tissues at
      different fortification levels (0.1-0.4 mg/kg for muscle, 0.2-1.2 mg/kg for
      liver, and 0.6-5.0 mg/kg for kidney) ranged from 80.7 to 91.3% with intraday and
      interday coefficient of variations less than 12.1%. The validated method was
      successfully applied to determine Kan in incurred samples, indicating that it can
      be used as a routine tool for the surveillance of Kan residue in swine tissues.

PMID- 19842124
TI  - Quantitative determination of 16 polycyclic aromatic hydrocarbons in soil samples
      using solid-phase microextraction.
AB  - A method for the determination of polycyclic aromatic hydrocarbons (PAHs) in soil
      samples using ultrasonic-assisted extraction with internal surrogates combined
      with solid-phase microextraction and GC-MS has been developed. Five kinds of
      commercial solid-phase microextraction fibers, 100 microm PDMS, 30 microm PDMS,
      65 microm PDMS/DVB, 50 microm DVB/CAR/PDMS and 85 microm PA, were compared to
      choose the optimal SPME fiber for extraction of PAHs. One hundred micrometers of
      PDMS fiber was found to be more suitable for the determination of PAHs due to its
      wider linear range, better repeatability, lower detection and more satisfactory
      efficacy than the other fibers. Under the recommended conditions, 100 microm PDMS
      fiber could provide low nanogram level detection limits with correlation
      coefficient greater than 0.98. The method was also applied to determine PAHs in a
      spiked soil sample, obtaining recoveries higher than 79.3%. A field study with
      naturally contaminated samples from local contaminated sites was carried out. The
      proposed method was found to be a reliable, inexpensive and simple preparation
      method for quantitative determination of 16 PAHs in soil samples.

PMID- 19842125
TI  - CE-ECL detection of gatifloxacin in biological fluid after clean-up using SPE.
AB  - A simple, rapid and sensitive CE method has been proposed for the determination
      of gatifloxacin in biological fluid. This method is based on the ECL reaction of
      gatifloxacin and tris(2,2'-bipyridyl)ruthenium(II) occurred in the end-column
      detection cell. Under the optimal conditions, gatifloxacin can be assayed within
      10 min over the concentration range of 5.0x10(-8)-5.0x10(-6) g/mL with the
      theoretical plate numbers of 18,000. The intra-day and inter-day precision of the
      signal intensity and the migration time shows acceptable reproducibility for the
      analysis of gatifloxacin. The presented method has been successfully applied to
      determine the concentrations of gatifloxacin in urine and blood samples after
      clean-up using C(18) SPE column.

PMID- 19842126
TI  - Multi-armed poly(L-glutamic acid)-graft-oligoethylenimine copolymers as efficient
      nonviral gene delivery vectors.
AB  - BACKGROUND: The application of polyethylenimine (PEI) in gene delivery has been
      severely limited by significant cytotoxicity that results from a nondegradable
      methylene backbone and high cationic charge density. It is therefore necessary to
      develop novel biodegradable PEI derivates for low-toxic, highly efficient gene
      delivery. METHODS: A series of novel cationic copolymers with various charge
      density were designed and synthesized by grafting different kinds of
      oligoethylenimine (OEI) onto a determinate multi-armed poly(L-glutamic acid)
      backbone. The molecular structures of multi-armed poly(L-glutamic acid)-graft-OEI
      (MP-g-OEI) copolymers were characterized using nuclear magnetic resonance,
      viscosimetry and gel permeation chromatography. Moreover, the MP-g-OEI/DNA
      complexes were measured by a gel retardation assay, dynamic light scattering and
      atomic force microscopy to determine DNA binding ability, particle size, zeta
      potential, complex formation and shape, respectively. MP-g-OEI copolymers were
      also evaluated in Chinese hamster ovary and human embryonic kidney-293 cells for
      their cytotoxicity and transfection efficiency. RESULTS: The particle sizes of MP
      g-OEI/DNA complexes were in a range of 109.6-182.6 nm and the zeta potentials
      were in a range of 29.2-44.5 mV above the N/P ratio of 5. All the MP-g-OEI
      copolymers exhibited lower cytotoxicity and higher gene transfection efficiency
      than PEI25k in the absence and presence of serum with different cell lines.
      Importantly, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay revealed that the cytotoxicity of MP-g-OEI copolymers varied with their
      molecular weight and charge density, and two of MP-g-OEI copolymers (OEI600-MP
      and OEI1800-MP) could achieve optimal transfection efficiency at a similar low
      N/P ratio as that for PEI25k. CONCLUSIONS: MP-g-OEI copolymers demonstrated
      considerable potential as nonviral vectors for gene therapy.

PMID- 19842127
TI  - Inverse shifting PCR based prenatal diagnosis of hemophilia-causative inversions
      involving int22h and int1h hotspots from chorionic villus samples.

PMID- 19842129
TI  - The biochemistry of drug metabolism--an introduction: part 7. Intra-individual
      factors affecting drug metabolism.
AB  - This review on intra-individual factors affecting drug metabolism completes our
      series on the biochemistry of drug metabolism. The article presents the molecular
      mechanisms causing intra-individual differences in enzyme expression and
      activity. They include enzyme induction by transcriptional activation and enzyme
      inhibition on the protein level. The influencing factors are of physiological,
      pathological, or external origin. Tissue characteristics and developmental age
      strongly influence enzyme-expression patterns. Further influencing factors are
      pregnancy, disease, or biological rhythms. Xenobiotics, drugs, constituents of
      herbal remedies, food constituents, ethanol, and tobacco can all influence enzyme
      expression or activity and, hence, affect drug metabolism.

PMID- 19842130
TI  - Verticillane derivatives from natural sources.

PMID- 19842128
TI  - Dopamine receptors modulate ethanol's locomotor-activating effects in preweanling
      rats.
AB  - Near the end of the second postnatal week motor activity is increased soon after
      ethanol administration (2.5 g/kg) while sedation-like effects prevail when blood
      ethanol levels reach peak values. This time course coincides with biphasic
      reinforcement (appetitive and aversive) effects of ethanol determined at the same
      age. The present experiments tested the hypothesis that ethanol-induced activity
      during early development in the rat depends on the dopamine system, which is
      functional in modulating motor activity early in ontogeny. Experiments 1a and 1b
      tested ethanol-induced activity (0 or 2.5 g/kg) after a D1-like (SCH23390; 0,
      .015, .030, or .060 mg/kg) or a D2-like (sulpiride; 0, 5, 10, or 20 mg/kg)
      receptor antagonist, respectively. Ethanol-induced stimulation was suppressed by
      SCH23390 or sulpiride. The dopaminergic antagonists had no effect on blood
      ethanol concentration (Experiments 2a and 2b). In Experiment 3, 2.5 g/kg ethanol
      increased dopamine concentration in striatal tissue as well as locomotor activity
      in infant Wistar rats. Adding to our previous results showing a reduction in
      ethanol induced activity by a GABA B agonist or a nonspecific opioid antagonist,
      the present experiments implicate both D1-like and D2-like dopamine receptors in
      ethanol-induced locomotor stimulation during early development. According to
      these results, the same mechanisms that modulate ethanol-mediated locomotor
      stimulation in adult rodents seem to regulate this particular ethanol effect in
      the infant rat.

PMID- 19842131
TI  - Antiproliferative and proapoptotic activities of a new class of pyrazole
      derivatives in HL-60 cells.
AB  - A series of N-substituted pyrazole derivatives have been synthesized and tested
      for their anticancer effect on the HL-60 leukaemia cell line. Four were active
      both in cell-growth inhibition and in inducing apoptosis. The inhibition of cell
      growth mainly reflects a compound-induced reduction in the number of cells in
      phases from S to M, whereas the induction of apoptosis involves inhibition of
      expression of Bcl-2 and enhanced expression of Bax with consequent reduced
      activation of the proapoptotic caspase 3. Finally, preliminary experiments
      carried out with tumor cells from myelogenous leukaemic patients showed that the
      compounds 4c, 4l, 4m, and 4n are indeed capable of inducing apoptosis.

PMID- 19842132
TI  - 4,5,6-Trisubstituted piperidinones as conformationally restricted ceramide
      analogues: synthesis and evaluation as inhibitors of sphingosine and ceramide
      kinases and as NKT cell-stimulatory antigens.
AB  - The conformationally based piperidinone sphingosine analogues 7, 8, 15, and 16
      were synthesized from allylic alcohol 34 via lactams 31 and 32. The L-arabino
      diol 7 and the L-ribo diol 8 were transformed into the amino alcohols 17-24. The
      L-gluco ceramide analogues 43, 46a, and 47, and the L-altro ceramide analogues
      51a and 52 were synthesized from either 31 or 32. The L-ribo diols 8 and 16, and
      the amino alcohols 19 and 20 inhibit sphingosine kinase 1 (SPHK1), while the L
      arabino analogues 7, 15, 17, and 18 are inactive. The L-arabino and the L-ribo
      dimethylamines 21-24, the L-gluco ceramide analogues 43, 46a, and 47, and the L
      altro ceramide analogues 51a and 52 did not block SPHK1. Neither the L-arabino
      diol 7 nor the L-ribo diol 8 inhibited SPHK2 or ceramide kinase. The L-arabino
      diols 7 and 15 stimulate invariant natural killer T (iNKT) cells when presented
      by living antigen-presenting cells (APC) and also by plate-bound human CD1d,
      whereas the L-ribo diols 8 and 16, the L-arabino amino alcohols 17-18, and the
      dimethylamines 21-22 did not activate iNKT cells. The L-gluco ceramide analogues
      43, 46a, and 47 had strongly stimulatory effects on iNKT cells when presented by
      living APC and also by plate-bound human CD1d, whereas the L-altro ceramide
      analogue 52 activated only weakly. All activatory compounds induced
      preferentially the release of pro-inflammatory cytokines, indicating the
      formation of a stable CD1d--lipid--T-cell receptor complex.

PMID- 19842134
TI  - Further Daphniphyllum alkaloids with insecticidal activity from the bark of
      Daphniphyllum macropodum M(IQ).
AB  - Two new Daphniphyllum alkaloids, macropodumines J and K (1 and 2, resp.),
      together with six known structurally related alkaloids, 3-8, were isolated from
      the bark of Daphniphyllum macropodum M(IQ). The structures of the new compounds 1
      and 2 were elucidated on the basis of a comprehensive analysis of their
      spectroscopic and chemical data. Macropodumine J (1) contains a CN group which is
      relatively rare in naturally occurring alkaloids. All isolated compounds were
      tested for their insecticidal activities against a number of insect species.
      Daphtenidine C (5) is the most active compound against Plutella xylostella. This
      is the first report of insecticidal properties of Daphniphyllum alkaloids.

PMID- 19842133
TI  - Chemical constituents from the whole plant of Gaultheria itoana Hayata.
AB  - Two new diterpenoids, 14,18-dihydroxyabieta-8,11,13-trien-7-one (1) and 13-acetyl
      14,18-dihydroxy-podocarpa-8,11,13-triene (2), together with eight known
      compounds, i.e., gaultheric acid (3), vanillic acid (4), 4-hydroxybenzoic acid
      (5), cinnamic acid (6), stearic acid (7), palmitic acid (8), beta-sitosterol (9),
      and stigmasterol (10), were isolated from the MeOH extract of the whole plant of
      Gaultheria itoana Hayata (Ericaceae). The structures of the new constituents were
      elucidated by spectroscopic methods (UV, IR, and 1D- and 2D-NMR) and by mass
      spectrometry (HR-ESI-MS). Among them, 1 and 2 were demonstrated to exhibit
      significant cytotoxic activity against the LNCaP cell line.

PMID- 19842135
TI  - Chemical constituents of Crinum asiaticum L. var. sinicum Baker and their
      cytotoxic activities.
AB  - A phytochemical investigation of the bulbs of Crinum asiaticum L. var. sinicum
      Baker resulted in the isolation of two new alkaloids, asiaticumines A and B (1
      and 2, resp.), together with 21 known compounds, including nine alkaloids, four
      amides, five phenolic compounds, and three flavonoids. All 23 compounds were
      isolated for the first time from Crinum asiaticum L. var. sinicum Baker. Their
      structures were elucidated by spectroscopic methods. In addition, ten alkaloids,
      1-10, were evaluated for their cytotoxic activities against human tumor cell
      lines A549, LOVO, HL-60, and 6T-CEM. Compounds 3, 4, and 7-10 selectively showed
      remarkable inhibition against one or more of the tested cell lines.

PMID- 19842137
TI  - Antioxidant activities of aqueous extract from Agrimonia pilosa Ledeb and its
      fractions.
AB  - Agrimonia pilosa Ledeb is used as the tonic for asthenia and fatigue in China.
      Considering that the energizing effect might be correlated with antioxidant
      properties, we investigated the antioxidant activities of aqueous extract (AE)
      from Agrimonia pilosa Ledeb by assessing radical-scavenging and anti-lipid
      peroxidation abilities. We found that AE shows a moderate antioxidant activity to
      scavenge DPPH*, O2(-)* and *OH and inhibit beta-carotene bleaching with IC(50)
      values of 13.0, 33.2, 351, and 11.9 microg/ml, respectively, while its AcOEt
      soluble fraction (ESF) and BuOH soluble fraction (BSF) exhibit remarkable
      efficiencies. The ESF's IC(50) values of scavenging DPPH*, O2(-)*, and *OH, and
      inhibiting beta-carotene bleaching are 5.6, 5.8, 171, and 7.6 mircog/ml,
      respectively, and those of BSF are 7.5, 8.4, 82.0, and 6.2 microg/ml,
      respectively. In addition, we found that there is a significant correlation
      between total phenol content and the antioxidant activity determined by O2(-)*
      and *OH scavenging, and beta-carotene-bleaching assays. Furthermore, HPLC
      analysis revealed the presence of quercetin, hyperoside, quercitrin, taxifoliol,
      luteolin-7-O-beta-D-glucopyranoside, and rutin in Agrimonia pilosa Ledeb. Thus,
      we suggest that the extracts from Agrimonia pilosa Ledeb, could be considered as
      natural antioxidant sources and dietary nutritional supplements to prevent
      oxidation-related diseases.

PMID- 19842138
TI  - Synthesis and Na(+)/H(+) exchanger-1 inhibitory activity of substituted
      (quinolinecarbonyl)guanidine derivatives.
AB  - The Na(+)/H(+) exchanger (NHE) is a protein expressed in many mammalian cell
      types. It is involved in intracellular pH (pH(i)) homeostasis by exchanging
      extracellular Na(+) for intracellular H(+). To date, nine NHE isoforms (NHE1
      NHE9) have been identified. NHE1 is the most predominant isoform expressed in
      mammalian cardiac muscle. A novel series of substituted
      (quinolinecarbonyl)guanidine derivatives were designed and synthesized as NHE
      inhibitors. Most compounds can inhibit NHE1-mediated platelet swelling in a
      concentration-dependent manner, among which compound 7f was the most active and
      more potent than cariporide. Furthermore, compound 7f has also been demonstrated
      to exhibit the in vivo cardioprotective effects against SD rat myocardial
      ischemic-reperfusion injury superior to those of cariporide.

PMID- 19842139
TI  - Maternal serum screening marker levels in women with a previous aneuploidy
      pregnancy.
AB  - OBJECTIVE: To re-evaluate in a larger cohort of patients if the maternal serum
      biochemical markers used in first trimester aneuploidy screening have the same
      marker distributions in pregnancies with a previous history of aneuploidy
      compared with those that have no previous history. METHODS: Information related
      to previous pregnancy history is routinely recorded as part of first trimester
      screening in three centres King George, Kings College and Fetal Medicine Centre,
      London. From the database, records were extracted for women who had a previous
      pregnancy diagnosed with trisomies 13, 18 or 21. For each woman with a previous
      aneuploidy, five unaffected pregnancies in women of the same maternal age and
      with no previous aneuploidy pregnancy were selected as controls. A comparison was
      made between the marker distributions for pregnancy associated plasma protein-A
      (PAPP-A) and free beta-human chronic gonadotrophin (beta-hCG) amongst the cases
      and controls using nonparametric statistical tests. RESULTS: A series of 8240
      controls were compared against group of 1032 cases with a previous trisomy 21,
      293 with a previous trisomy 18 and 158 with a previous trisomy 13. Cases with
      multiple previous trisomies were excluded. There were no significant differences
      in the level of free beta-hCG; however, in cases of trisomy 21 and trisomy 13 the
      levels of PAPP-A were increased by 5 and 16%, respectively. CONCLUSION: Risk
      calculation algorithms may need to take account of the increased PAPP-A levels in
      women with a previous trisomy 21 or trisomy 13.

PMID- 19842140
TI  - Extensive lymphadenectomy in colorectal cancer with isolated para-aortic lymph
      node metastasis below the level of renal vessels.
AB  - BACKGROUND AND OBJECTIVES: The effects of isolated metastatic node dissection in
      the para-aortic region have not been established in colorectal cancer (CRC). The
      authors undertook to evaluate the role of para-aortic lymph node (PALN)
      dissection in CRC with isolated PALN metastasis. METHODS: Between January 1993
      and March 2006, 24 patients underwent PALN dissection for isolated PALN
      metastasis from CRC. Patients with distant metastases other than to PALNs, or
      with nodal metastasis above the celiac axis were excluded. The control group was
      composed of 53 patients with isolated PALN metastasis below the level of the
      renal hilum that was not surgically removed. RESULTS: Median disease-free
      interval after PALN dissection was 14 months. The postoperative complication rate
      was 27.8%, which was not significantly different from that of the control group.
      Median survivals in the PALN dissection and control groups were 64 (range, 17
      111) and 33 (range, 24-42) months, respectively. The overall 5-year survival rate
      was 53.4% in the PALN dissection group, versus 12.0% in the control group (P =
      0.045). CONCLUSIONS: The findings of this study suggest that PALN dissection
      increases the survival of patients with isolated PALN metastasis from CRC, and
      that it has a tolerable morbidity rate.

PMID- 19842145
TI  - Dynamic measurement of the volumetric oxygen transfer coefficient in fermentation
      systems.

PMID- 19842146
TI  - Festschrift in honor of Lynn P. Rehm, PhD, ABPP.

PMID- 19842147
TI  - Xenopus axin-related protein: a link between its centrosomal localization and
      function in the Wnt/beta-catenin pathway.
AB  - The Wnt/beta-catenin signaling pathway regulates cell proliferation and cell fate
      determination in multiple systems. However, the subcellular localization of Wnt
      pathway components and the significance of this localization for the pathway
      regulation have not been extensively analyzed. Here we report that Xenopus Axin
      related protein (XARP), a component of the beta-catenin destruction complex, is
      localized to the centrosome. This localization of XARP requires the presence of
      the DIX domain and an adjacent region. Since other components of the Wnt pathway
      have also been shown to associate with the centrosome, we tested a hypothesis
      that the beta-catenin destruction complex operates at the centrosome. However,
      XARP mutants with poor centrosomal localization revealed an enhanced rather than
      decreased ability to antagonize the Wnt/beta-catenin pathway. Our data are
      consistent with the idea that the inactivation of XARP at the centrosome is an
      important regulatory point in Wnt signaling.

PMID- 19842148
TI  - Structure of cholesterol/lipid ordered domains in monolayers and single hydrated
      bilayers.

PMID- 19842149
TI  - Systematic metal variation and solvent and hydrogen-gas storage in supramolecular
      nanoballs.

PMID- 19842150
TI  - Supramolecular amphiphiles based on a water-soluble charge-transfer complex:
      fabrication of ultralong nanofibers with tunable straightness.

PMID- 19842154
TI  - Asymmetric dehydrative cyclization of omega-hydroxy allyl alcohols catalyzed by
      ruthenium complexes.

PMID- 19842151
TI  - Total synthesis of zoanthenol.

PMID- 19842156
TI  - The derivatization of bioplatform molecules by using KF/alumina catalysis.

PMID- 19842157
TI  - High value products from waste: grape pomace extract--a three-in-one package for
      the synthesis of metal nanoparticles.
AB  - Metal nanoparticles of Au, Ag, Pd, and Pt have been synthesized in aqueous media
      using red grape pomace as a reducing agent and a capping agent. The particles are
      formed within a few seconds when exposed to microwave irradiation at a power
      level as low as 50 W. Particles could be formed at room temperature, but they
      tend to be amorphous in nature except for gold. A detailed study on the
      morphology of the ensuing particles with various reaction conditions has been
      carried out.

PMID- 19842158
TI  - Fabrication of complex micelles with tunable shell for application in controlled
      drug release.
AB  - At room temperature, diblock copolymers of PLA-b-PNIPAM and PEG-b-PLA self
      assembled into complex micelles with a PLA core and a mixed PEG/PNIPAM shell. By
      increasing the temperature, these complex micelles could be converted into a core
      shell-corona structure composed of a PLA core, a collapsed PNIPAM shell and a
      soluble PEG corona, and the PEG chains stretched from the inner core to outside,
      leading to the formation of PEG channels. The PEG channels could be used for the
      exchange of substance between the core and the external environment. Compared
      with core-shell micelles, complex micelles with a core-shell-corona structure
      could avoid the burst diffusion in the release of ibuprofen and inhibit the
      degradation of PLA by lipase to a certain extent.

PMID- 19842159
TI  - MR metabolomics of fecal extracts: applications in the study of bowel diseases.
AB  - NMR-based metabolomics is becoming a useful tool in the study of body fluids and
      has a strong potential to contribute to disease diagnosis. While applications on
      urine and serum have been the focus to date, there are a number of other body
      fluids that are readily available and could potentially be used for metabolomics
      based disease diagnosis. One such body fluid is stool or fecal extract. Given its
      contact with and transient stay in the colon and rectum, stool carries a lot of
      useful information regarding the health/disease status of both the colon and the
      rectum. This could be particularly useful for the non-invasive diagnosis of
      colorectal cancer and inflammatory bowel disease--the two bowel diseases that are
      very common and pose significant public health problems. Different methodological
      considerations including the collection of sample, the storage of sample, the
      preparation of sample, NMR acquisition parameters, experimental conditions and
      data analysis methods are discussed. Results obtained in the detection of
      colorectal cancer and in the differentiation of the two major forms of
      inflammatory bowel disease (i.e. ulcerative colitis and Crohn's disease) are
      presented. This is concluded with a brief discussion on the future of MR
      metabolomics of fecal extracts.

PMID- 19842160
TI  - The impact of killing in war on mental health symptoms and related functioning.
AB  - This study examined the mental health and functional consequences associated with
      killing combatants and noncombatants. Using the National Vietnam Veterans
      Readjustment Study (NVVRS) survey data, the authors reported the percentage of
      male Vietnam theater veterans (N = 1200) who killed an enemy combatant, civilian,
      and/or prisoner of war. They next examined the relationship between killing in
      war and a number of mental health and functional outcomes using the clinical
      interview subsample of the NVVRS (n = 259). Controlling for demographic variables
      and exposure to general combat experiences, the authors found that killing was
      associated with posttraumatic stress disorder symptoms, dissociation, functional
      impairment, and violent behaviors. Experiences of killing in war are important to
      address in the evaluation and treatment of veterans.

PMID- 19842161
TI  - Pain severity in eating disorders predicts longer inpatient hospitalization.
AB  - OBJECTIVE: This study examined pain intensity (PI) in eating disorders. METHOD:
      Comparisons between inpatients (N = 208) reporting moderate to severe pain (HiP)
      and no pain or mild pain (LoP) at admission were made, and the relationship
      between PI and treatment response was examined. RESULTS: Patients with HiP were
      older, had a greater likelihood of having a bingeing and/or purging diagnosis,
      and reported greater body dissatisfaction, drive for thinness, depressive
      symptomatology, and neuroticism in comparison to those with LoP. They were also
      more likely to report widespread pain, to catastrophize about pain and to use
      praying and hoping to cope with pain. PI was associated with longer length of
      inpatient hospitalization, even after controlling for degree of underweight,
      depressive symptomatology, and neurotic personality features. DISCUSSION: This is
      the first observation of a relationship between pain and health care utilization
      in eating disorders. The results imply that pain management is an important
      component of treatment.

PMID- 19842162
TI  - Nitric oxide conduction by the brain aquaporin AQP4.
AB  - Involvement of aquaporins in gas conduction across the membrane and the
      physiological significance of this process have attracted marked attention from
      both experimental and theoretical studies. Previous work demonstrated that AQP1
      is permeable to both CO(2) and O(2). Here we employ various simulation techniques
      to examine the permeability of the brain aquaporin AQP4 to NO and O(2) and to
      describe energetics and pathways associated with these phenomena. The energy
      barrier to NO and O(2) permeation through AQP4 central pore is found to be only
      approximately 3 kcal mol(-1). The results suggest that the central pore of AQP4,
      similar to that of AQP1, can indeed conduct gas molecules. Interestingly, despite
      a longer and narrower central pore, AQP4 appears to provide an energetically more
      favorable permeation pathway for gas molecules than AQP1, mainly due to the
      different orientation of its charged residues near the pore entrance. Although
      the low barrier against gas permeation through AQP4 indicates that it can
      participate in gas conduction across the cellular membrane, physiological
      relevance of the phenomenon remains to be established experimentally,
      particularly since pure lipid bilayers appear to present a more favorable pathway
      for gas conduction across the membrane. With an energy well of -1.8 kcal mol(-1),
      the central pore of AQP4 may also act as a reservoir for NO molecules to
      accumulate in the membrane.

PMID- 19842163
TI  - A binding free energy decomposition approach for accurate calculations of the
      fidelity of DNA polymerases.
AB  - DNA polymerase beta (pol beta) is a small eukaryotic enzyme with the ability to
      repair short single-stranded DNA gaps that has found use as a model system for
      larger replicative DNA polymerases. For all DNA polymerases, the factors
      determining their catalytic power and fidelity are the interactions between the
      bases of the base pair, amino acids near the active site, and the two magnesium
      ions. In this report, we study effects of all three aspects on human pol beta
      transition state (TS) binding free energies by reproducing a consistent set of
      experimentally determined data for different structures. Our calculations
      comprise the combination of four different base pairs (incoming pyrimidine
      nucleotides incorporated opposite both matched and mismatched purines) with four
      different pol beta structures (wild type and three mutants). We generate three
      fragments of the incoming deoxynucleoside 5'-triphosphate-TS and run separate
      calculations for the neutral base part and the highly charged triphosphate part,
      using different dielectric constants in order to account for the specific
      dielectric response. This new approach improves our ability to predict the effect
      of matched and mismatched base pairing and of mutations in DNA polymerases on
      fidelity and may be a useful tool in studying the potential of DNA polymerase
      mutations in the development of cancer. It also supports our point of view with
      regards to the origin of the structural control of fidelity, allowing for a
      quantified description of the fidelity of DNA polymerases.

PMID- 19842165
TI  - Severity of anxiety and work-related outcomes of patients with anxiety disorders.
AB  - BACKGROUND: This study examined associations between anxiety and work-related
      outcomes in an anxiety disorders clinic population, examining both pretreatment
      links and the impact of anxiety change over 12 weeks of treatment on work
      outcomes. Four validated instruments were used to also allow examination of their
      psychometric properties, with the goal of improving measurement of work-related
      quality of life in this population. METHODS: Newly enrolled adult patients
      seeking treatment in a university-based anxiety clinic were administered four
      work performance measures: Work Limitations Questionnaire (WLQ), Work
      Productivity and Activity Impairment Questionnaire (WPAI), Endicott Work
      Productivity Scale (EWPS), and Functional Status Questionnaire Work Performance
      Scale (WPS). Anxiety severity was determined using the Beck Anxiety Inventory
      (BAI). The Clinical Global Impressions, Global Improvement Scale (CGI-I) was
      completed by patients to evaluate symptom change at a 12-week follow-up. Two
      severity groups (minimal/mild vs. moderate/severe, based on baseline BAI score)
      were compared to each other on work measures. RESULTS: Eighty-one patients
      provided complete baseline data. Anxiety severity groups did not differ in job
      type, time on job, job satisfaction, or job choice. Patients with greater anxiety
      generally showed lower work performance on all instruments. Job advancement was
      impaired for the moderate/severe group. The multi-item performance scales
      demonstrated better validity and internal consistency. The WLQ and the WPAI
      detected change with symptom improvement. CONCLUSION: Level of work performance
      was generally associated with severity of anxiety. Of the instruments tested, the
      WLQ and the WPAI questionnaire demonstrated acceptable validity and internal
      reliability.

PMID- 19842164
TI  - Association study between GABA receptor genes and anxiety spectrum disorders.
AB  - BACKGROUND: Human anxiety disorders are complex diseases with relatively unknown
      etiology. Dysfunction of the Gamma-aminobutyric acid (GABA) system has been
      implicated in many neuropsychiatric conditions, including anxiety and depressive
      disorders. In this investigation, we explored four GABA receptor genes for their
      possible associations with genetic risk for anxiety disorders and depression.
      METHODS: Our study sample consisted of 589 cases and 539 controls selected from a
      large population-based twin registry based upon a latent genetic risk factor
      shared by several anxiety disorders, major depression, and neuroticism. We
      subjected these to a two-stage protocol, in which all candidate genetic markers
      were screened for association in stage 1 (N=376), the positive results of which
      were tested for replication in stage 2 (N=752). We analyzed data from 26 single
      nucleotide polymorphisms (SNPs) from four GABA receptor genes: GABRA2, GABRA3,
      GABRA6, and GABRG2. RESULTS: Of the 26 SNPs genotyped in stage 1, we identified
      two markers in GABRA3 that met the threshold (P < or = .1) to be tested in stage
      2. Phenotypic associations of these two markers failed to replicate in stage 2.
      CONCLUSIONS: These findings suggest that common variation in the GABRA2, GABRA3,
      GABRA6, and GABRG2 genes does not play a major role in liability to anxiety
      spectrum disorders.

PMID- 19842166
TI  - Design of multispecific protein sequences using probabilistic graphical modeling.
AB  - In nature, proteins partake in numerous protein- protein interactions that
      mediate their functions. Moreover, proteins have been shown to be physically
      stable in multiple structures, induced by cellular conditions, small ligands, or
      covalent modifications. Understanding how protein sequences achieve this
      structural promiscuity at the atomic level is a fundamental step in the drug
      design pipeline and a critical question in protein physics. One way to
      investigate this subject is to computationally predict protein sequences that are
      compatible with multiple states, i.e., multiple target structures or binding to
      distinct partners. The goal of engineering such proteins has been termed
      multispecific protein design. We develop a novel computational framework to
      efficiently and accurately perform multispecific protein design. This framework
      utilizes recent advances in probabilistic graphical modeling to predict sequences
      with low energies in multiple target states. Furthermore, it is also geared to
      specifically yield positional amino acid probability profiles compatible with
      these target states. Such profiles can be used as input to randomly bias high
      throughput experimental sequence screening techniques, such as phage display,
      thus providing an alternative avenue for elucidating the multispecificity of
      natural proteins and the synthesis of novel proteins with specific
      functionalities. We prove the utility of such multispecific design techniques in
      better recovering amino acid sequence diversities similar to those resulting from
      millions of years of evolution. We then compare the approaches of prediction of
      low energy ensembles and of amino acid profiles and demonstrate their
      complementarity in providing more robust predictions for protein design.

PMID- 19842167
TI  - Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed
      African American population.
AB  - BACKGROUND: Genetic polymorphisms that influence serotonin (5-hydroxytryptamine,
      5HT) neurotransmission are candidates for contributing to susceptibility to
      posttraumatic stress disorder (PTSD). The objective of our study was to determine
      if a variable length polymorphism for the promoter regions of the 5HT transporter
      (5HTTLPR), and/or a substitution polymorphism in the promoter region for the
      5HT2A receptor, would be associated with PTSD in a trauma exposed population of
      adult African-Americans. METHODS: Using a case control design, 118 participants
      recruited from the primary care clinics and the campus of a historically black
      university who met inclusion criteria including trauma exposure provided blood
      samples for genomic DNA. PTSD criteria were determined by the Clinician
      Assessment of PTSD Scale (CAPS) and criteria for other psychiatric disorders by
      the Structured Clinical Interview for DSM-IV (SCID). 5HTTLPR and 5HT2A-1438A/G
      were genotyped using established methods. Associations of genotypes with lifetime
      PTSD, and models testing associations of allele "dose", were analyzed. RESULTS:
      Fifty-five (47%) participants met lifetime criteria for PTSD and 26 (22%) met
      criteria for (mostly comorbid) major depression. The 5HT2A (lower expressing) G
      allele was significantly associated with PTSD. We did not find significant
      associations with 5HTTLPR. CONCLUSIONS: Our findings suggest a relationship
      between genetic variation in the 5HT2A promoter region and PTSD.

PMID- 19842168
TI  - The impact of neuropsychological functioning on treatment outcome in pediatric
      obsessive-compulsive disorder.
AB  - BACKGROUND: Scant research has examined the effect of neuropsychological (NP)
      functioning on treatment outcome in pediatric obsessive-compulsive disorder
      (OCD). This study sought to address this gap in existing research. METHODS: A
      total of 63 youths were included in this study and asked to complete the Rey
      Osterrieth Complex Figure (ROCF) and specific subtests of the Wechsler
      Intelligence Scale for Children, Third Edition (WISC-III). RESULTS: Analyses
      suggest that 5 min recall accuracy (raw score) and percent recall from the ROCF,
      assessed before treatment may be predictors of treatment response among children
      with OCD. What is more, exploratory post hoc analyses indicated that performance
      on these ROCF tasks is particularly relevant among youths receiving cognitive
      behavior therapy (CBT) alone. These results may be driven by executive
      functioning ability. Additional analyses suggest a relationship between age,
      symptom severity, and NP functioning on select tasks from both the ROCF and WISC
      III. CONCLUSIONS: Although alternative explanations exist, these findings suggest
      that poorer performance on the ROCF and, in turn, poorer response to treatment,
      particularly among those youths receiving CBT alone, may be due to executive
      functioning difficulties. Clinicians and researchers should be sensitive to this
      fact and may warrant modification(s) to existing treatment protocols. Limitations
      to this study, however, suggest the need for replication and extension of these
      findings in the future.

PMID- 19842169
TI  - Linkage and association studies of anxiety disorders.

PMID- 19842170
TI  - Prevalence and risk factors for posttraumatic stress disorder: a cross-sectional
      study among survivors of the Wenchuan 2008 earthquake in China.
AB  - BACKGROUND: The impact of the May 2008 Wenchuan earthquake, measuring a massive
      8.0 on the surface wave magnitude scale, on public health in China has been
      significant and multifaceted. In light of extant data on prevalence and risk
      factors for posttraumatic stress disorder (PTSD) after other natural diasters, we
      collected data from the Wenchuan earthquake survivors to estimate the prevalence
      of PTSD and to characterize a range of PTSD risk factors. METHODS: A cross
      sectional multicluster sample survey of 446 respondents (201 from the Qiang
      ethnic-minority group, 245 the majority Han Chinese group) was conducted in
      August 2008 in Beichuan county, Sichuan province, a region that was severely
      affected by the earthquake. In total, 240 households were represented, with a
      mean of 2.2 respondents per household. Data were collected from structured
      interviews and the Harvard Trauma Questionnaire (HTQ) and DSM-IV criteria were
      used to diagnose PTSD. RESULTS: The prevalence of PTSD was 45.5% (203/446). Low
      household income, being from an ethnic minority, living in a shelter or temporary
      house, death in family, and household damage were factors significantly related
      to increased odds of PTSD. CONCLUSIONS: PTSD is common after a major disaster.
      Postdisaster mental health recovery programs that include early identification,
      ongoing monitoring, preventive and intervention programs, and sustained
      psychosocial support are needed for the highest-risk population, namely, the
      bereaved, people without incomes and those with serious household damage. These
      populations may also benefit from governmental and nongovernmental programs that
      provide social and economic support, as suggested by earlier studies.

PMID- 19842171
TI  - PTSD, depression, and their comorbidity in relation to suicidality: cross
      sectional and prospective analyses of a national probability sample of women.
AB  - BACKGROUND: A growing body of literature implicates major depressive disorder
      (MDD) and posttraumatic stress disorder (PTSD) as risk factors for suicidal
      ideation (SI) and suicide attempts (SA), though research has not adequately
      examined their differential contributions to increasing suicide risk
      prospectively or cross-sectionally. METHODS: The contribution of these disorders
      and their comorbidity to SI and SA was examined using a national household
      probability sample of women (N=3,085) and covarying for trauma history, substance
      abuse, and demographic variables. RESULTS: Cross-sectional analyses indicated
      that lifetime comorbidity of MDD and PTSD were associated with much higher
      prevalence of SI than either diagnosis alone; prevalence of SI was elevated and
      comparable for PTSD and MDD only. Comorbid diagnosis and PTSD only groups
      displayed greater prevalence of SA than those with MDD only. Lastly, a 2-year
      prospective analysis indicated that PTSD only at baseline was predictive of
      greater subsequent SI risk than MDD only, though comorbid diagnosis did not
      differ from either PTSD only or MDD only. CONCLUSIONS: PTSD appears to be a
      particularly strong predictor of SI and SA. Overall, only 16% of women with
      lifetime SA did not have a history of MDD or PTSD, highlighting the importance of
      assessing these variables when assessing suicide risk.

PMID- 19842173
TI  - Embryogenesis and ossification of Emydura subglobosa (Testudines, Pleurodira,
      Chelidae) and patterns of turtle development.
AB  - Using the Standard Event System (SES) to study patterns of vertebrate
      development, we describe a series of 17 embryos of the pleurodire turtle Emydura
      subglobosa. Based on a sequence heterochrony analysis including 23 tetrapod taxa,
      we identified autapomorphic developmental shifts that characterise Testudines,
      Cryptodira, and Pleurodira. The main results are that Testudines are
      characterised by an autapomorphic late neck development, whereas pleurodires and
      cryptodires show a different developmental timing of the mandibular process.
      Additionally, we described the ossification pattern of E. subglobosa and compared
      the data to those of five other turtles. Pleurodires show the epiplastron to
      ossify before or simultaneously with maxilla and dentary. In contrast,
      cryptodires show a later ossification of this bone. Because evolutionary
      developmental studies on turtles have previously focused only on "model
      organisms" that all belong to Cryptodira, we underline the necessity to include a
      pleurodire taxon for a more comprehensive, phylogenetically more informative
      approach.

PMID- 19842174
TI  - Comparative expression of zebrafish lats1 and lats2 and their implication in
      gastrulation movements.
AB  - Large tumor suppressor (Lats) is a Ser/Thr kinase, and it presents an important
      function in tumor suppression. lats was originally identified in Drosophila and
      recently in mammals. In mammals, it contains two homologues, lats1 and lats2. In
      the present study, lats1 and lats2 were characterized from zebrafish (Danio
      rerio), which is the first report of lats in a nonmammalian vertebrate. The
      primary structure, genomic organization, and phylogenesis of lats from different
      species were studied, and the results suggest that lats1 is the direct descendant
      of invertebrate lats, whereas lats2 is formed by genome duplication. In
      zebrafish, both lats genes are maternally expressed, while they show distinctly
      different expression profiles during gastrulation. lats1 is almost ubiquitously
      expressed through development, and lats2 is more prominently expressed in the non
      neural ectoderm region of zebrafish gastrula. Most intriguingly, as revealed by
      cell tracing and gene expression analysis, morpholino-mediated knockdown of
      either lats1 or lats2 led to obvious defects of cell migration in gastrulation,
      indicating the functional significance of lats in gastrulation movements.

PMID- 19842175
TI  - Developmental expression of Smoc1 and Smoc2 suggests potential roles in fetal
      gonad and reproductive tract differentiation.
AB  - SMOC1 and SMOC2 are matricellular proteins thought to influence growth factor
      signaling, migration, proliferation, and angiogenesis. We examined the expression
      and regulation of Smoc1 and Smoc2 in fetal gonad/mesonephros complexes to
      discover possible roles for these genes in gonad and mesonephros development.
      Smoc1 was upregulated at approximately E10.75 in a center-to-poles wave in pre
      Sertoli and pre-granulosa cells and its expression was greatly reduced in Wt1,
      Sf1, and Fog2 mutants. After E13.5, Smoc1 was downregulated in an anterior-to
      posterior wave in granulosa cells but persisted in Sertoli cells, suggesting a
      sexually dimorphic requirement in supporting cell lineage differentiation. Smoc2
      was expressed in Leydig cells, mesonephroi, and Wnt4 mutant ovaries, but not
      wildtype ovaries. Using organ culture, we determined that Smoc2 expression was
      dependent on Hedgehog signaling in testes, mesonephroi, and kidneys. Overall,
      these results demonstrate that SMOC1 and SMOC2 may mediate intercellular
      signaling and cell type-specific differentiation during gonad and reproductive
      tract development.

PMID- 19842177
TI  - Foxg1 is required for proper separation and formation of sensory cristae during
      inner ear development.
AB  - The vestibular portion of the inner ear, the three semicircular canals and their
      sensory cristae, is responsible for detecting angular head movements. It was
      proposed that sensory cristae induce formation of their non-sensory components,
      the semicircular canals. Here, we analyzed the inner ears of Foxg1(-/-) mouse
      mutants, which display vestibular defects that are in conflict with the above
      model. In Foxg1(-/-) ears, the lateral canal is present without the lateral
      ampulla, which houses the lateral crista. Our gene expression analyses indicate
      that at the time when canal specification is thought to occur, the prospective
      lateral crista is present, which could have induced lateral canal formation prior
      to its demise. Our genetic fate-mapping analyses indicate an improper separation
      between anterior and lateral cristae in Foxg1(-/-) mutants. Our data further
      suggest that a function of Foxg1 in the inner ear is to restrict sensory fate.

PMID- 19842178
TI  - Functional characterization of cardiac progenitor cells and their derivatives in
      the embryonic heart post-chamber formation.
AB  - There is scant information on the fate of cardiac progenitor cells (CPC) in the
      embryonic heart after chamber specification. Here we simultaneously tracked three
      lineage-specific markers (Nkx2.5, MLC2v, and ANF) and confirmed that CPCs with an
      Nkx2.5+MLC2v-ANF- phenotype are present in the embryonic (E) day 11.5 mouse
      ventricular myocardium. We demonstrated that these CPCs could give rise to
      working cardiomyocytes and conduction system cells. Using a two-photon imaging
      analysis, we found that the majority of CPCs are not capable of developing Ca2+
      transients in response to beta-adrenergic receptor stimulation. In contrast,
      Nkx2.5+ cells expressing MLC2v but not ANF are capable of developing functional
      Ca2+ transients. We showed that Ca2+ transients could be invoked in
      Nkx2.5+MLC2v+ANF+ cells only upon inhibition of Gi, muscarinic receptors, or
      nitric oxide synthase (NOS) signaling pathways. Our data suggest that these
      inhibitory pathways may delay functional specification in a subset of developing
      ventricular cells.

PMID- 19842181
TI  - A developmental study of enteric neuron migration in the grasshopper using
      immunological probes.
AB  - Motility of enteric plexus neurons in the grasshopper Locusta migratoria depends
      critically on the NO/cGMP signaling cascade. This is reflected in a strong NO
      dependent cGMP staining in migrating enteric midgut neurons. In contrast, first
      cGMP immunoreactivity (cGMP-IR) in the foregut enteric ganglia was detected
      clearly after the main migratory processes have taken place. Thus, expression of
      cGMP-IR in migrating neurons is a distinct phenomenon restricted to neurons
      forming midgut and foregut plexus, that does not occur during convergence of
      neurons forming the enteric ganglia. Analysis of time lapse video microscopy of
      migrating midgut neurons together with an immunofluorescence study of midgut
      cellular structures suggests a contribution of the midgut musculature to enteric
      neuron guidance. Additionally, during midgut plexus formation a fasciculating
      signal for enteric neuron neurites appears to be provided by the cell adhesion
      molecule Fasciclin I.

PMID- 19842180
TI  - Osteoblast maturation occurs in overlapping proximal-distal compartments during
      fin regeneration in zebrafish.
AB  - During fin regeneration, osteoblasts must continually differentiate for outgrowth
      of the bony fin rays. Bone maturity increases in a distal-proximal manner, and
      osteoblast maturation can be detected similarly when following gene expression.
      We find that early markers for osteoblast differentiation are expressed in a
      discrete domain at the distal end of the fin, just proximal to the adjacent
      germinal compartment of dividing cells. Matrix genes, required at later stages
      developmentally, are expressed in a population of cells proximally to the early
      genes. A marker for mature osteoblasts is expressed in cells further proximal.
      These domains of gene expression are partially overlapping, perhaps revealing
      additional levels of osteoblast maturity. We suggest a model for growth where new
      cells are continually added to the distal-most osteoblast compartment, while
      osteoblasts in more proximal locations differentiate, thus translating
      developmental time to location on the proximal-distal axis.

PMID- 19842182
TI  - Progenitor cell maturation in the developing vertebrate retina.
AB  - Progenitor cells in the developing retina initially divide so that each division
      produces two cells that divide again. Subsequently, progenitor cells change their
      mode of division so that one or both cells produced by a division can withdraw
      from the mitotic cycle and differentiate. We asked how these two progenitor cell
      stages differ molecularly and what controls the switch in the mode of division.
      We show that early preneurogenic progenitor cells express the transcription
      factor, Sox2, and the Notch ligand, Delta1. More mature neurogenic progenitor
      cells express Sox2 and the bHLH transcription factor, E2A, and not Delta1. Notch
      signaling maintains progenitor cells in the preneurogenic state. Sonic hedgehog
      expressed by newly differentiating cells initiates maturation of progenitor cells
      from preneurogenic to neurogenic at the neurogenic front, possibly by down
      regulating Delta1 expression. Our results show that the preneurogenic-to
      neurogenic transition is a highly organized unidirectional step made in unison by
      neighboring cells.

PMID- 19842183
TI  - Sequence and expression of the zebrafish alpha-actinin gene family reveals
      conservation and diversification among vertebrates.
AB  - Alpha-actinins are actin microfilament crosslinking proteins. Vertebrate actinins
      fall into two classes: the broadly-expressed actinins 1 and 4 (actn1 and actn4)
      and muscle-specific actinins, actn2 and actn3. Members of this family have
      numerous roles, including regulation of cell adhesion, cell differentiation,
      directed cell motility, intracellular signaling, and stabilization of f-actin at
      the sarcomeric Z-line in muscle. Here we identify five zebrafish actinin genes
      including two paralogs of ACTN3. We describe the temporal and spatial expression
      patterns of these genes through embryonic development. All zebrafish actinin
      genes have unique expression profiles, indicating specialization of each gene. In
      particular, the muscle actinins display preferential expression in different
      domains of axial, pharyngeal, and cranial musculature. There is no identified
      avian actn3 and approximately 16% of humans are null for ACTN3. Duplication of
      actn3 in the zebrafish indicates that variation in actn3 expression may promote
      physiological diversity in muscle function among vertebrates.

PMID- 19842184
TI  - Role of VEGF and tissue hypoxia in patterning of neural and vascular cells
      recruited to the embryonic heart.
AB  - We hypothesized that oxygen gradients and hypoxia-responsive signaling may play a
      role in the patterning of neural or vascular cells recruited to the developing
      heart. Endothelial progenitor and neural cells are recruited to and form branched
      structures adjacent to the relatively hypoxic outflow tract (OFT) myocardium from
      stages 27-32 (ED6.5-7.5) of chick development. As determined by whole mount
      confocal microscopy, the neural and vascular structures were not anatomically
      associated. Adenoviral delivery of a VEGF trap dramatically affected the
      remodeling of the vascular plexus into a coronary tree while neuronal branching
      was normal. Both neuronal and vascular branching was diminished in the hearts of
      embryos incubated under hyperoxic conditions. Quantitative analysis of the
      vascular defects using our recently developed VESGEN program demonstrated reduced
      small vessel branching and increased vessel diameters. We propose that vascular
      and neural patterning in the developing heart share dependence on tissue oxygen
      gradients but are not interdependent.

PMID- 19842185
TI  - Chromosomal position mediates spinal cord expression of a dbx1a enhancer.
AB  - Dbx homeodomain proteins are important for the production of multiple spinal cord
      cell types. To examine the regulation of Dbx genes in more detail, we have
      generated transgenic zebrafish in which fluorescent protein expression is driven
      by predicted dbx1a enhancers. We identified three areas of sequence conservation
      upstream of the dbx1a coding sequence and generated fluorescent reporter
      constructs driven by these predicted enhancer elements and the endogenous dbx1a
      promoter. In multiple stable insertions of a 3.5-kb enhancer fragment, we
      observed that there was additional reporter expression in the dorsal spinal cord
      not normally observed by dbx1a in situ hybridization. In addition, these lines
      exhibited only transient reporter expression, unlike the endogenous gene.
      Surprisingly, a single insertion line expressed the reporter in the endogenous
      pattern, indicating that other local regulatory elements modulate gene expression
      through the 3.5-kb enhancer.

PMID- 19842186
TI  - Mechanisms for split localization of Fgf10 expression in early lung development.
AB  - In early lung development, epithelial tubes (lung buds) intrude into mesenchyme
      covered with pleural cells (lung border), and form tree-like networks, by means
      of repeated use of morphogenetic processes: "elongation," "terminal bifurcation,"
      and "lateral budding." When a bud is elongating, a peak of Fgf10 expression is
      formed in the mesenchyme near the tip; whereas when terminal bifurcation and
      lateral budding occur, two separate peaks are formed instead. To explain the
      spatial pattern of Fgf10 expression, we developed a mathematical model for the
      regulation of Fgf10 expression with geometrical conditions including shapes of
      the lung buds and the lung border. Different localization patterns of Fgf10
      expression can be explained by the geometrical conditions. Fgf10 expression has a
      single peak when a length between the tip of lung bud and the lung border is
      large. When the length is small, Fgf10 expression has two peaks, whose location
      depends on the curvature of lung border.

PMID- 19842187
TI  - Homozygous disruption of the Tip60 gene causes early embryonic lethality.
AB  - Tat-interactive protein 60 (Tip60) is a member of the MYST family, proteins of
      which are related by an atypical histone acetyltransferase (HAT) domain. Although
      Tip60 has been implicated in cellular activities including DNA repair, apoptosis,
      and transcriptional regulation, its function during embryonic development is
      unknown. We ablated the Tip60 gene (Htatip) from the mouse by replacing exons 1-9
      with a neomycin resistance cassette. Development and reproduction of wild-type
      and heterozygous animals were normal. However, homozygous ablation of the Tip60
      gene caused embryolethality near the blastocyst stage of development, as
      evidenced by inability of cells in Tip60-null blastocysts to hatch and survive in
      culture. Monitoring cell proliferation and death by detecting EdU-substituted DNA
      and TUNEL labeling revealed suppression of cell proliferation concomitant with
      increased cell death as Tip60-null cells attempted to hatch from blastocysts.
      These findings indicate that Tip60 is essential for cellular survival during the
      blastocyst-gastrula transition of embryogenesis.

PMID- 19842188
TI  - Fzd3 and Fzd6 deficiency results in a severe midbrain morphogenesis defect.
AB  - Wnt/beta-catenin signaling controls the proper development of the mid-/hindbrain
      region (MHR) and of midbrain dopaminergic (mDA) neurons, but the Frizzled (Fzd)
      receptors transducing these signals are still unknown. Fzd3 is expressed
      throughout the mouse anterior neural tube, whereas Fzd6 is restricted to the MHR.
      We show that the MHR is properly established and mDA neurons develop normally in
      Fzd6(-/-) mutants, but the number of mDA neurons is initially reduced and
      recovers at later stages in Fzd3(-/-) embryos. Fzd3(-/-); Fzd6(-/-) double
      mutants exhibit a severe midbrain morphogenesis defect consisting of collapsed
      brain ventricles, apparent thickening of the neuroepithelium, focal disruption of
      the ventricular basal lamina and protrusion of individual cells, and increased
      proliferation at later stages, despite a normal closure of the anterior neural
      tube and the rescue of the mDA defect in these embryos. Fzd3 and Fzd6 thus
      control proper midbrain morphogenesis by a yet unknown mechanism in the mouse.

PMID- 19842189
TI  - Autosomal recessive diseases among the Athabaskans of the southwestern United
      States: recent advances and implications for the future.
AB  - Genetic and linguistic data suggest that the Na-Dene, of which the Athabaskans
      are the largest group, are part of a later immigration into the Americas than the
      first Amerind immigration. Whether a second and third immigration can be
      separated seems unlikely but continued cross-Bering Strait exchanges may have
      masked what was a greater separation in the past. The movement of tribes into
      Siberia appears to have involved a genetic bottleneck leading to at least one
      disease allele shared by Eskimo/Aleuts and Navajos and a second possibly shared
      by the Navajo and a Siberian population, but not the same Siberian population
      that share deep linguistic affinities with the Navajo. A second bottleneck
      appears to have occurred with the migration of Athabaskans from Northwest North
      America to the Southwestern United States along the Rocky Mountains. This
      bottleneck is reflected in several rare recessive diseases shared by the Navajo
      and Apache. Finally, the Navajo were captured and imprisoned under conditions
      which led to severe population loss. This, and the "hiding away" of a small
      number of Navajos in what is now the Western portion of the reservation, led to a
      Navajo-specific bottleneck(s) resulting in an increased frequency of several rare
      recessive diseases among the Navajo. Prejudice against human genetic research is
      high among the Southwestern Athabaskans but attempts to bridge the gap are now
      occurring. The involvement of Navajo scientists in this process is especially
      encouraging.

PMID- 19842190
TI  - Characterization of a new X-linked mental retardation syndrome with microcephaly,
      cortical malformation, and thin habitus.
AB  - X-linked mental retardation (XLMR) affects 1-2/1,000 males and accounts for
      approximately 10% of all mental retardation (MR). We have ascertained a syndromic
      form of XLMR segregating within a five-generation family with seven affected
      males. Prominent characteristics include mild to severe MR, cortical
      malformation, microcephaly, seizures, thin build with distinct facial features
      including a long and thin face, epicanthic folds, almond-shaped eyes, upslanting
      palpebral fissures and micrognathia and behavioral problems. Carrier females have
      normal physical appearance and intelligence. This combination of features is
      unreported and distinct from Lujan-Fryns syndrome, Snyder-Robinson syndrome, and
      zinc finger DHHC domain-containing 9-associated MR. We propose the name of this
      new syndrome to be CK syndrome.

PMID- 19842191
TI  - Progeroid syndrome with scleroderma-like skin changes associated with homozygous
      R435C LMNA mutation.
AB  - Hutchinson-Gilford progeria is a rare genetic disorder resulting from mutations
      in the LMNA gene encoding lamin A/C. In addition to the classical phenotype
      usually caused by the 1824C>T mutation of LMNA, a number of atypical progeroid
      syndromes have been described. They have some distinct features, such as skeletal
      deformities or scleroderma-like skin changes. The underlying defect is usually a
      homozygous mutation of LMNA, or a combined defect of LMNA and another gene, for
      example, ZMPSTE-24. We present a 2-year-old girl born to consanguineous parents
      affected by progeroid syndrome with scleroderma-like skin changes. Genetic
      analysis revealed the homozygous LMNA mutation 1303C>T (R435C). The same
      heterozygous mutation was found in the patient's parents and 11 other family
      members. The progeroid syndrome in our patient shares the signs of two
      laminopathies: progeria and restrictive dermatopathy. Two other children in the
      family died at the age of 2 due to a disease similar to that in the proposita. On
      the basis of the family pedigree we presume that these children probably had the
      same homozygous LMNA mutation. Scleroderma-like skin changes in infants,
      associated with growth retardation and dysmorphic features, suggest premature
      aging syndrome, requiring genetic testing and counseling of asymptomatic carriers
      of LMNA mutations.

PMID- 19842192
TI  - Brainstem disconnection associated with nodular heterotopia and proatlantal
      arteries.
AB  - We report on a patient with brainstem disconnection associated with
      periventricular nodular heterotopia and bilateral proatlantal intersegmental
      arteries. The patient was a girl born after 37 weeks of gestation with birth
      weight of 1,938 g. Polyhydroamnios and lack of swallowing movement were noted on
      fetal ultrasonography. No spontaneous body movement or respiration was observed
      after birth, whereas facial movement was preserved. She had marked generalized
      weakness and absent deep tendon reflexes. She remains alive and hospitalized at 4
      years of age but requires mechanical ventilation and feeding through a
      gastrostomy tube. MRI showed absence of the lower pons and the medulla oblongata
      associated with hypoplasia of the cerebellar vermis and hemispheres. In addition,
      ventriculomegaly and periventricular nodular heterotopia were observed in the
      cerebrum. MR angiography demonstrated the absence of vertebral arteries and
      presence of bilateral proatlantal intersegmental arteries arising from the
      external carotid arteries. Array-comparative genomic hybridization analysis did
      not show any genomic copy number aberrations. No mutation was found in the FLNA
      gene or the EN2 gene. The constellation of the malformations of our patient
      suggested that genes related to the development of the central nervous and
      vascular system may be involved in the pathogenesis of brainstem disconnection.

PMID- 19842193
TI  - Severe hypertriglyceridemia and recurrent pancreatitis in a girl with type Ia
      glycogen storage disease and type III hyperlipoproteinemia.

PMID- 19842194
TI  - Genital anomalies in three male siblings with Simpson-Golabi-Behmel syndrome.
AB  - Simpson-Golabi-Behmel syndrome is an X-linked recessive overgrowth disorder
      characterized by prenatal onset of overgrowth, characteristic facies, and
      frequently mild to severe mental retardation. In addition, a number of other
      characteristics including supernumerary nipples, a grooved tongue or chin, chest
      wall malformations, and mild genital anomalies are frequently seen as well. Here
      we present three brothers with Simpson-Golabi-Behmel syndrome, all of which had
      cryptorchidism with one also having chordee of the penis, hypospadius, and
      penoscrotal transposition. While severe genital anomalies have been reported
      rarely in patients with Simpson-Golabi-Behmel syndrome, no individuals with such
      anomalies prior to this report had survived beyond the neonatal period.

PMID- 19842195
TI  - A de novo direct duplication of 16q22.1 --> q23.1 in a boy with midface
      hypoplasia and mental retardation.

PMID- 19842196
TI  - Molecular characterization of a monosomy 1p36 presenting as an Aicardi syndrome
      phenocopy.
AB  - Monosomy 1p36 is the most frequent terminal deletion known in Humans. Typical
      craniofacial features, developmental delay/mental retardation, seizures and
      sensorineural defects characterize 1p36 deletion syndrome. Aicardi syndrome (AIS)
      is a rare genetic disorder characterized by chorioretinal lacunae, corpus
      callosum agenesis and infantile spasms responsible for mental retardation. By
      screening DNA from diagnosed AIS patients with oligonucleotide array-based
      comparative genomic hybridization (aCGH), we report a 1p36 monosomy in this
      study. There were no other deletions or duplications. Regarding clinical
      criteria, the patient did not have the typical facial appearance commonly
      described for 1p36 monosomy patients. We showed that this 1p36 monosomy
      corresponded to combined interstitial and terminal de novo deletions of the
      chromosome 1 leading to an 11.73 Mb deletion confirmed with qPCR. By
      microsatellite markers and FISH analyses, we have concluded that this deletion
      occurred on maternal chromosome 1 during oogenesis. We did find some clinical
      features shared by the 1p36 monosomy and AIS: infantile spasms, corpus callosum
      dysgenesis, ophthalmological abnormalities, and skeletal malformations. To date,
      no relationship between these two phenotypes has been established. We conclude
      that the monosomy 1p36 should be considered in the differential diagnosis of AIS.

PMID- 19842197
TI  - Conversion disorder in women with the FMR1 premutation.
AB  - Women with fragile X mental retardation (FMR1) gene premutations (55-200 CGG
      repeats) were until recently believed to be unaffected. It is now known that up
      to 8% of older female FMR1 premutation carriers develop fragile X-associated
      tremor/ataxia syndrome (FXTAS). Female carriers may also develop primary ovarian
      insufficiency, thyroid disease, hypertension, seizures, peripheral neuropathy,
      and fibromyalgia. We present a 60-year-old woman with FMR1 premutation who had
      depression, anxiety, and conversion disorder with seizures. The FMR1 premutation
      with its associated mRNA toxicity is postulated as an underlying neurobiological
      mechanism of conversion symptoms, through functional and structural neural
      dysconnectivity.

PMID- 19842198
TI  - Parental perceived value of a diagnosis for intellectual disability (ID): a
      qualitative comparison of families with and without a diagnosis for their child's
      ID.
AB  - Although new technologies such as array genomic hybridization to diagnosis the
      cause of intellectual disabilities (ID) are exciting to clinicians, the value of
      an etiological diagnosis to the families of affected children is largely unknown.
      Parents of 20 children with ID, 10 with and 10 without a causal or an etiological
      diagnosis were interviewed in depth about the value they place on such a
      diagnosis. They were asked about experiences acquiring services, use of support
      groups, interactions with family and friends, and opinions on prenatal diagnosis.
      Parents were also asked whether their child's diagnostic status had influenced
      these events or affected the couple's reproductive decisions. Finally, parents
      were asked whether their interest regarding the importance of an etiological
      diagnosis had changed over time. Interview transcripts were analyzed to determine
      values parents place on etiological diagnoses and comparisons were made between
      the two groups. These parents felt the need for a diagnosis most intensely when
      developmental concerns were first noted, and most parents agreed that this
      intensity diminished over time. All would have preferred to have an etiological
      diagnosis, but for some the only reason was curiosity. Validation was the most
      important value attributed to a diagnosis: it offered legitimacy for the child's
      behavior and appearance. However, a descriptive label, such as autism, was often
      more useful to parents than a rare but specific etiological diagnosis.
      Surprisingly, between the two groups there were no differences in the parents'
      perceptions or experiences related to the presence or absence of an etiological
      diagnosis for their child's ID.

PMID- 19842199
TI  - Characterization of a de novo complex chromosomal rearrangement in a patient with
      cri-du-chat and trisomy 5p syndromes.
AB  - Two syndromes with abnormalities of the short arm of chromosome 5 have been
      described: cri-du-chat (resulting from 5p deletion) and trisomy 5p. We report for
      the first time a patient with both syndromes, resulting from a complex
      chromosomal rearrangement with an inverted duplication of 5p13.1-p14.2, a
      deletion of 5p14.2-pter, and a duplication of 5p12, characterized by array-CGH
      and BAC clones. The patient showed phenotypic characteristics of both syndromes
      and died at 3 months of age as a result of cardiorespiratory failure, probably
      associated with the clinical severity of the trisomy 5p syndrome. We propose a
      potential causative mechanism for this rearrangement.

PMID- 19842200
TI  - A new case of syndromic craniosynostosis with cryptic 19p13.2-p13.13 deletion.

PMID- 19842201
TI  - Fukutin gene retrotransposal insertion in a non-Japanese Fukuyama congenital
      muscular dystrophy (FCMD) patient.
AB  - Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive
      disorder, characterized by severe muscular dystrophy associated with brain
      malformation. FCMD is the second most common form of muscular dystrophy and one
      of the most common autosomal recessive diseases among the Japanese population;
      however, no typical FCMD cases have been reported in any other population. In
      this study, we report on the first identification of a Chinese FCMD patient; our
      findings are supported by clinical, histological, and magnetic resonance imaging
      (MRI) evidence, as well as fukutin gene mutational analyses. The patient
      presented with neonatal hypotonia, seizures, and delayed motor and speech
      development. Additional testing revealed cerebral and cerebellar gyrus
      abnormalities with white matter signal intensity changes, elevated serum creatine
      kinase (CK) levels, and dystrophic skeletal muscle with alpha-dystroglycan
      hypoglycosylation, and normal beta-dystroglycan and merosin expression. Genetic
      analysis of the fukutin gene showed one copy with a Japanese founder 3-kilobase
      (kb) retrotransposal insertion in the 3'-non-coding region and the other copy
      with a known c.139C>T mutation. This is the first FCMD case reported in the
      Chinese population and the first case in which the 3-kb insertion has been found
      outside of the Japanese population. This report emphasizes the importance of
      considering the fukutin founder mutation for diagnostic purposes outside of
      Japan.

PMID- 19842202
TI  - "Essentially" pure trisomy 3q27 --> qter: further delineation of the partial
      trisomy 3q phenotype.
AB  - Partial duplication 3q is a well defined clinical entity characterized by growth
      retardation, cryptorchism, microcephaly, and characteristic dysmorphisms. Most
      patients present with large duplications or are associated with a second
      chromosomal imbalance, which makes the definition of the phenotype difficult.
      Here, we report on a 4-year and 8-month-old girl with pre- and postnatal
      measurements in the high normal range, developmental delay, minor dysmorphic
      features, and a de novo unbalanced 3/4 translocation with trisomy 3q27 --> qter
      and monosomy of the subtelomeric region of 4p. Conventional karyotyping, FISH
      with probes from the Wolf-Hirschhorn syndrome critical region and chromosome 4p
      locus-specific probes, microsatellite marker-based haplotyping, and SNP
      microarray copy number analysis revealed a terminal 4p deletion of less than 500
      kb with a breakpoint distal to the Wolf-Hirschhorn syndrome critical region, a
      chromosome 3q duplication of around 15.3 Mb, with origin of the rearrangement in
      paternal meiosis. Thus, our case clearly characterizes the phenotype of pure
      partial duplication 3q more exactly, and moreover, indicates that small
      chromosome rearrangements might lead to growth in the upper normal range or even
      cause overgrowth.

PMID- 19842203
TI  - Comprehensive ZEB2 gene analysis for Mowat-Wilson syndrome in a North American
      cohort: a suggested approach to molecular diagnostics.
AB  - Mowat-Wilson syndrome is a genetic condition characterized by a recognizable
      facial phenotype in addition to moderate to severe cognitive disability with
      severe speech impairment and variable multiple congenital anomalies. The
      anomalies may include Hirschsprung disease, heart defects, structural eye
      anomalies including microphthalmia, agenesis of the corpus callosum, and
      urogenital anomalies. Microcephaly, seizure disorder and constipation are common.
      All typical cases result from haploinsufficiency of the ZEB2 (also known as
      ZFHX1B or SIP-1) gene, with over 100 distinct mutations now described.
      Approximately 80% of patients have a nonsense or frameshift mutation detectable
      by sequencing, with the rest having gross deletions necessitating a dosage
      sensitive assay. Here we report on the results of comprehensive molecular testing
      for 27 patients testing positive for MWS. Twenty-one patients had a nonsense,
      frameshift, or splice site mutation identified by sequencing; 14 of which
      localized to exon 8 and 17 of which are novel. Six patients had deletions in the
      ZEB2 gene, including two novel partial gene deletions. This report, the first
      such analysis in North American patients, adds to the growing list of both novel
      pathogenic mutations associated with MWS, as well as other variants in the ZEB2
      gene. In addition, we suggest an economical testing strategy.

PMID- 19842204
TI  - The lack of clinical distinction between the hypermobility type of Ehlers-Danlos
      syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome).

PMID- 19842205
TI  - Three novel mutations of the IRF6 gene with one associated with an unusual
      feature in Van der Woude syndrome.
AB  - Van der Woude syndrome (VWS) is a dominantly inherited disorder characterized by
      cleft lip with or without cleft palate and lip pits. It remains the most common
      syndromic form of oral clefts. Mutations in the interferon regulatory factor 6
      (IRF6) gene have been identified in patients with VWS. We reported three
      unrelated families with lower lip anomalies. Two had lower lip pits, a cardinal
      sign of VWS, but the other had a heart-shaped mass on lower lip without pits,
      oral clefts, or hypodontia. This isolated anomaly has not been previously
      observed in VWS. We performed mutation analysis by PCR-sequencing the entire
      coding region of the IRF6 gene. Three potentially pathogenic mutations, c.145C>T
      (p.Q49X), c.171T>G (p.F57L), and 1306C>G (p.L436V) were successfully identified.
      All the missense mutations were not detected in 100 unaffected ethnic-matched
      control chromosomes and have never been previously reported. The p.Q49X and
      p.F57L mutations were located in the highly conserved DNA binding domain while
      the p.L436V was located at the carboxy-terminal region. This study reported an
      undescribed clinical feature of VWS and three novel mutations, expanding the
      phenotypic spectrum of VWS and mutational spectrum of IRF6.

PMID- 19842207
TI  - Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in
      patients with chronic hepatitis B.
AB  - Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17)-mediated immune response
      has been demonstrated to play a critical role in inflammation-associated disease;
      however, its role in chronic hepatitis B virus (HBV) infection remains unknown.
      Here we characterized peripheral and intrahepatic Th17 cells and analyzed their
      association with liver injury in a cohort of HBV-infected patients including 66
      with chronic hepatitis B (CHB), 23 with HBV-associated acute-on-chronic liver
      failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating
      Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF
      (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were
      also found to be largely accumulated in the livers of CHB patients. The increases
      in circulating and intrahepatic Th17 cells positively correlated with plasma
      viral load, serum alanine aminotransferase levels, and histological activity
      index. In vitro, IL-17 can promote the activation of myeloid dendritic cells and
      monocytes and enhance the capacity to produce proinflammatory cytokines IL-1beta,
      IL-6, tumor necrosis factor (TNF)-alpha, and IL-23 in both CHB patients and
      healthy subjects. In addition, the concentration of serum Th17-associated
      cytokines was also increased in CHB and ACLF patients. CONCLUSION: Th17 cells are
      highly enriched in both peripheral blood and liver of CHB patients, and exhibit a
      potential to exacerbate liver damage during chronic HBV infection.

PMID- 19842206
TI  - Mapping of Wnt, frizzled, and Wnt inhibitor gene expression domains in the avian
      otic primordium.
AB  - Wnt signaling activates at least three different pathways involved in development
      and disease. Interactions of secreted ligands and inhibitors with cell-surface
      receptors result in the activation or regulation of particular downstream
      intracellular cascades. During the developmental stages of otic vesicle closure
      and beginning morphogenesis, the forming inner ear transcribes a plethora of Wnt
      related genes. We report expression of 23 genes out of 25 tested in situ
      hybridization probes on tissue serial sections. Sensory primordia and Frizzled
      gene expression share domains, with Fzd1 being a continuous marker. Prospective
      nonsensory domains express Wnts, whose transcripts mainly flank prosensory
      regions. Finally, Wnt inhibitor domains are superimposed over both prosensory and
      nonsensory otic regions. Three Wnt antagonists, Dkk1, SFRP2, and Frzb are
      prominent. Their gene expression patterns partly overlap and change over time,
      which adds to the diversity of molecular microenvironments. Strikingly,
      prosensory domains express Wnts transiently. This includes: 1) the prosensory
      otic region of high proliferation, neuroblast delamination, and programmed cell
      death at stage 20/21 (Wnt3, -5b, -7b, -8b, -9a, and -11); and 2) sensory
      primordia at stage 25 (Wnt7a and Wnt9a). In summary, robust Wnt-related gene
      expression shows both spatial and temporal tuning during inner ear development as
      the otic vesicle initiates morphogenesis and prosensory cell fate determination.

PMID- 19842208
TI  - ACLU lawsuit questions the patenting of breast cancer genes.

PMID- 19842212
TI  - Spectrum and consequences of SMC1A mutations: the unexpected involvement of a
      core component of cohesin in human disease.
AB  - SMC1A encodes a structural component of the cohesin complex, which is necessary
      for sister chromatid cohesion. In addition to its canonical role, cohesin has
      been shown to be involved in gene expression regulation and maintenance of genome
      stability. Recently, it has been demonstrated that mutations in the SMC1A gene
      are responsible for Cornelia de Lange syndrome (CdLS). CdLS is a genetically
      heterogeneous multisystem developmental disorder with variable expressivity,
      typically characterized by consistent facial dysmorphia, upper extremity
      malformations, hirsutism, cardiac defects, growth and cognitive retardation,
      gastrointestinal abnormalities, and other systemic involvement. SMC1A mutations
      have also been identified in colorectal cancers. So far a total of 26 different
      mutations of the SMC1A gene have been reported. All mutations reported to date
      are either missense or small in-frame deletions that maintain the open reading
      frame and presumably result in a protein with residual function. The mutations
      involve all domains of the protein but appear to cluster in key functional loci.
      At the functional level, elucidation of the effects that specific SMC1A mutations
      have on cohesin activity will be necessary to understand the etiopathology of
      CdLS and its possible involvement in tumorigenesis. In this review, we summarize
      the current knowledge of SMC1A mutations.

PMID- 19842213
TI  - Shadow autozygosity mapping by linkage exclusion (SAMPLE): a simple strategy to
      identify the genetic basis of lethal autosomal recessive disorders.
AB  - Autozygosity mapping has been invaluable for determining the genetic basis of
      lethal autosomal recessive disorders, but this approach remains challenging
      because DNA from affected individuals may often be unavailable or of insufficient
      quality for extensive molecular genetic studies. To circumvent these
      difficulties, we developed a computer program called "SAMPLE" (for shadow
      autozygosity mapping by linkage exclusion) to enhance autozygosity mapping
      through the empirical analysis of haplotypes of unaffected individuals in
      consanguineous families. Single nucleotide polymorphism (SNP) genotyping of
      unaffected individuals in complex consanguineous pedigrees is used to infer
      limited chromosomal regions compatible with linkage to a potential disease locus,
      and to allow the immediate prioritization of potential regions of interest.
      Further limited genotyping then enables the rapid confirmation and fine mapping
      of a disease locus. We demonstrate the utility of this strategy by using
      genotyping data from only parents and unaffected siblings, in three
      consanguineous families affected with Meckel-Gruber syndrome, to correctly infer
      the location of the MKS3/TMEM67 locus on chromosome 8q22.1. This strategy is
      practicable only with the recent advances in whole genome genotyping by high
      density SNP microarrays, and could not be easily implemented in approaches that
      rely on microsatellite markers. SAMPLE is available at
      http://dna.leeds.ac.uk/sample/.

PMID- 19842214
TI  - Deep sequencing to reveal new variants in pooled DNA samples.
AB  - We evaluated massive parallel sequencing and long-range PCR (LRP) for rare
      variant detection and allele frequency estimation in pooled DNA samples. Exons 2
      to 16 of the MUTYH gene were analyzed in breast cancer patients with Illumina's
      (Solexa) technology. From a pool of 287 genomic DNA samples we generated a single
      LRP product, while the same LRP was performed on 88 individual samples and the
      resulting products then pooled. Concentrations of constituent samples were
      measured with fluorimetry for genomic DNA and high-resolution melting curve
      analysis (HR-MCA) for LRP products. Illumina sequencing results were compared to
      Sanger sequencing data of individual samples. Correlation between allele
      frequencies detected by both methods was poor in the first pool, presumably
      because the genomic samples amplified unequally in the LRP, due to DNA quality
      variability. In contrast, allele frequencies correlated well in the second pool,
      in which all expected alleles at a frequency of 1% and higher were reliably
      detected, plus the majority of singletons (0.6% allele frequency). We describe
      custom bioinformatics and statistics to optimize detection of rare variants and
      to estimate required sequencing depth. Our results provide directions for
      designing high-throughput analyses of candidate genes.

PMID- 19842216
TI  - Surgical outcome of carcinosarcoma of the gall bladder: a review.
AB  - Carcinosarcoma, which comprises less than one percent of all gall bladder
      neoplasms, is characterized by the presence of variable proportions of
      carcinomatous and sarcomatous elements. Recently, several reports have described
      patients suffering from carcinosarcoma of the gall bladder. However, there are no
      large studies regarding the clinicopathologic features, therapeutic management,
      and surgical outcome of this disease because the number of patients who undergo
      resection of gall bladder carcinosarcoma at a single institution is limited. A
      Medline search was performed using the keywords 'gall bladder' and
      'carcinosarcoma'. Additional articles were obtained from references within the
      papers identified by the Medline search. Optimal adjuvant chemotherapy and/or
      radiotherapy protocols for carcinosarcoma of the gall bladder have not been
      established. Curative surgical resection offers the only chance for long-term
      survival from this disease. The outcome of 36 patients who underwent surgical
      resection for carcinosarcoma of the gall bladder was poor; the 3-year overall
      survival rate was only 31.0% and the median survival time was 7.0 mo. Since the
      postoperative prognosis of carcinosarcoma of the gall bladder is worse than that
      of adenocarcinoma, new adjuvant chemotherapies and/or radiation techniques are
      essential for improvement of surgical outcome.

PMID- 19842215
TI  - Biochemical mechanisms in drug-induced liver injury: certainties and doubts.
AB  - Drug-induced liver injury is a significant and still unresolved clinical problem.
      Limitations to knowledge about the mechanisms of toxicity render incomplete the
      detection of hepatotoxic potential during preclinical development. Several
      xenobiotics are lipophilic substances and their transformation into hydrophilic
      compounds by the cytochrome P-450 system results in production of toxic
      metabolites. Aging, preexisting liver disease, enzyme induction or inhibition,
      genetic variances, local O(2) supply and, above all, the intrinsic molecular
      properties of the drug may affect this process. Necrotic death follows
      antioxidant consumption and oxidation of intracellular proteins, which determine
      increased permeability of mitochondrial membranes, loss of potential, decreased
      ATP synthesis, inhibition of Ca(2+)-dependent ATPase, reduced capability to
      sequester Ca(2+) within mitochondria, and membrane bleb formation. Conversely,
      activation of nucleases and energetic participation of mitochondria are the main
      intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells
      are inducers of hepatocellular injury and targets for damage. Activation of the
      immune system promotes idiosyncratic reactions that result in hepatic necrosis or
      cholestasis, in which different HLA genotypes might play a major role. This
      review focuses on current knowledge of the mechanisms of drug-induced liver
      injury and recent advances on newly discovered mechanisms of liver damage. Future
      perspectives including new frontiers for research are discussed.

PMID- 19842217
TI  - Multifocal stenosing ulceration of the small intestine.
AB  - Several reports have described an apparently uncommon clinicopathological
      disorder that is characterized by multifocal stenosing small-intestinal
      ulceration. Compared to Crohn's disease, the ulcers are not transmural and
      typically remain shallow, and involve only the mucosa and submucosa. The disorder
      seems to be localized in the jejunum and proximal ileum only, and not the distal
      ileum or colon. Only nonspecific inflammatory changes are present without giant
      cells or other typical features of granulomatous inflammation. Most patients
      present clinically with recurrent obstructive events that usually respond to
      steroids, surgical resection, or both. With the development of newer imaging
      modalities to visualize the small-intestinal mucosa, such as double-balloon
      enteroscopy, improved understanding of the long-term natural history of this
      apparently distinctive disorder should emerge.

PMID- 19842218
TI  - Systematic review of Chinese herbal medicine for functional constipation.
AB  - Constipation is a common gastrointestinal complaint in clinical practice,
      affecting an estimated 27% of the population. Many patients are disappointed by
      current conventional treatments and, therefore, seek help from complementary and
      alternative medicine (CAM). Traditional Chinese medicine, is the most important
      part of CAM and has been practiced for treating diseases and promoting the health
      of humans for thousands of years, and has become a popular alternative choice.
      Although there are many Chinese herbal medicine (CHM) interventions available,
      and some have been verified by clinical trials, their efficacy and safety are
      still questioned by both patients and health care providers worldwide. The
      purposes of this review are, first, to appraise the qualities of individual study
      designs in the new Cochrane approach. Second, the benefits of individual CHM
      interventions or individual types of CHM intervention for the treatment of
      functional constipation are analyzed. Finally, valid and comprehensive
      conclusions are drawn, if applicable, in order to make clinical recommendations.

PMID- 19842219
TI  - Characterization of CD133+ parenchymal cells in the liver: histology and culture.
AB  - AIM: To reveal the characteristics of CD133(+) cells in the liver. METHODS: This
      study examined the histological characteristics of CD133(+) cells in non
      neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the
      biological characteristics of CD133(+) cells derived from human hepatocellular
      carcinoma (HCC) or cholangiocarcinoma cell lines. RESULTS: Immunostaining
      revealed constant expression of CD133 in non-neoplastic and neoplastic biliary
      epithelium, and these cells had the immunophenotype CD133(+)/CK19(+)/HepPar-1(-).
      A small number of CD133(+)/CK19(-)/HepPar-1(+) cells were also identified in HCC
      and combined hepatocellular and cholangiocarcinoma. In addition, small ductal
      structures, resembling the canal of Hering, partly surrounded by hepatocytes were
      positive for CD133. CD133 expression was observed in three HCC (HuH7, PLC5 and
      HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence
      activated cell sorting (FACS) revealed that CD133(+) and CD133(-) cells derived
      from HuH7 and HuCCT1 cells similarly produced CD133(+) and CD133(-) cells during
      subculture. To examine the relationship between CD133(+) cells and the side
      population (SP) phenotype, FACS was performed using Hoechst 33342 and a
      monoclonal antibody against CD133. The ratios of CD133(+)/CD133(-) cells were
      almost identical in the SP and non-SP in HuH7. In addition, four different
      cellular populations (SP/CD133(+), SP/CD133(-), non-SP/CD133(+), and non
      SP/CD133(-)) could similarly produce CD133(+) and CD133(-) cells during
      subculture. CONCLUSION: This study revealed that CD133 could be a biliary and
      progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect
      tumor-initiating cells in cell lines.

PMID- 19842220
TI  - Short-term celecoxib intervention is a safe and effective chemopreventive for
      gastric carcinogenesis based on a Mongolian gerbil model.
AB  - AIM: To evaluate the optimal intervention point of a selective cyclooxygenase-2
      (COX-2) inhibitor, celecoxib, for inhibiting Helicobacter pylori (H. pylori)
      associated gastric carcinogenesis in Mongolian gerbils (MGs). METHODS: One
      hundred and twelve MGs were divided into six groups (A-F). One hundred gerbils
      were inoculated with H. pylori (groups A-E). Twelve gerbils were inoculated with
      vehicle broth only (group F). After 4 wk, they were given N'-methyl-N'-nitro-N
      nitroso-guanidine (MNNG) (50 microg/mL) in the drinking water for 20 wk. In
      groups B-E, the animals were given the stock celecoxib (10 mg/kg per day) diet
      from the 21st, 31st, 21st and 41st week respectively. The periods of
      administering celecoxib were 30, 20, 20, and 15 wk respectively. On the 51st
      week, the animals were sacrificed for histological examination. Local PCNA
      expression was examined by the immunohistochemistry method. The expression of COX
      2 protein was assessed by western blot. Analysis used the chi(2) test. The
      difference was regarded as significant when P value was less than 0.05. RESULTS:
      Seventeen percent (17/100) of H. pylori-infected MGs developed gastric cancer.
      All of these lesions were well-differentiated adenocarcinoma. The incidence rates
      of adenocarcinoma in groups A-F were 40%, 0%, 0%, 20%, 25%, and 0% respectively.
      The inflammatory scores were higher in group B than in other groups. There was no
      inflammatory response noted in group F. Celecoxib treatment resulted in a
      significant reduction in the proliferation of H. pylori-infected mucosal cells
      (groups B, C and D) (P < 0.01). The expression of COX-2 protein was significantly
      attenuated in the groups which were celecoxib-treated for more than 20 wk (groups
      B, C, D). The groups treated with celecoxib had a significantly lower rate of
      advanced gastric cancer (34% vs 75%, P < 0.001) There were no sudden deaths in
      any of the groups. CONCLUSION: Short-term treatment with celecoxib has an anti
      carcinogenic effect, and resulted in less severe inflammation and inhibited the
      invasive degree of gastric cancer.

PMID- 19842221
TI  - Milk protein IgG and IgA: the association with milk-induced gastrointestinal
      symptoms in adults.
AB  - AIM: To study the association between serum levels of milk protein IgG and IgA
      antibodies and milk-related gastrointestinal symptoms in adults. METHODS: Milk
      protein IgG and IgA antibodies were determined in serum samples of 400 subjects
      from five outpatient clinics in Southern Finland. Subjects were randomly selected
      from a total of 1900 adults undergoing laboratory investigations in primary care.
      All 400 participants had completed a questionnaire on abdominal symptoms and
      dairy consumption while waiting for the laboratory visit. The questionnaire
      covered the nature and frequency of gastrointestinal problems, the provoking food
      items, family history and allergies. Twelve serum samples were disqualified due
      to insufficient amount of sera. The levels of specific milk protein IgG and IgA
      were measured by using the ELISA technique. The association of the milk protein
      specific antibody level was studied in relation to the milk-related
      gastrointestinal symptoms and dairy consumption. RESULTS: Subjects drinking milk
      (n = 265) had higher levels of milk protein IgG in their sera than non-milk
      drinkers (n = 123, P < 0.001). Subjects with gastrointestinal problems related to
      milk drinking (n = 119) consumed less milk but had higher milk protein IgG levels
      than those with no milk-related gastrointestinal symptoms (n = 198, P = 0.02).
      Among the symptomatic subjects, those reporting dyspeptic symptoms had lower milk
      protein IgG levels than non-dyspeptics (P < 0.05). However, dyspepsia was not
      associated with milk drinking (P = 0.5). The association of high milk protein IgG
      levels with constipation was close to the level of statistical significance.
      Diarrhea had no association with milk protein IgG level (P = 0.5). With regard to
      minor symptoms, flatulence and bloating (P = 0.8), were not associated with milk
      protein IgG level. Milk protein IgA levels did not show any association with milk
      drinking or abdominal symptoms. The levels of milk protein IgA and IgG declined
      as the age of the subjects increased (P < 0.004). CONCLUSION: Milk protein IgG
      but not milk IgA seems to be associated with self-reported milk-induced
      gastrointestinal symptoms.

PMID- 19842222
TI  - Effects of fasting and preoperative feeding in children.
AB  - AIM: To investigate whether children should undergo surgery without a long period
      of fasting after feeding. METHODS: Eighty children with inguinoscrotal disorders
      (aged 1-10 years) were studied prospectively. They were divided into eight groups
      that each contained 10 children who were fed normal liquid food (NLF) and a high
      calorie diet (HCD) 2, 3, 4 and 5 h before surgery, in two doses at 6-h intervals.
      NLF was given to four groups and HCD to the other four. In all groups, glucose,
      prealbumin and cortisol levels in the blood were measured twice: just after oral
      feeding and just before the operation. After the establishment of adequate
      anesthesia, gastric residue liquid was measured with a syringe. RESULTS: Blood
      glucose levels in all patients fed NLF and HCD were high, except in patients in
      the HCD-4 group. There was no significant difference in the blood prealbumin
      levels. There was a significant increase in the blood cortisol levels in the NLF
      2 (14.4 +/- 5.7), HCD-2 (13.2 +/- 6.0), NLF-3 (10.9 +/- 6.4), and HCD-5 (6.8 +/-
      5.7) groups (P < 0.05). CONCLUSION: The stress of surgery may be tolerated by
      children when they are fed up to 2 h before elective surgery.

PMID- 19842223
TI  - APRI as a predictor of early viral response in chronic hepatitis C patients.
AB  - AIM: To evaluate the aspartate aminotransferase (AST) to platelet ratio index
      (APRI) as a predictive factor of early viral response in chronic hepatitis C
      naive patients. METHODS: We performed an ambispective case-control study. We
      enrolled chronic hepatitis C naive patients who were evaluated to start therapy
      with PEGylated interferon alpha-2b (1.5 mug/kg per week) and ribavirin (> 75 kg:
      1200 mg and < 75 kg: 1000 mg). Patients were allocated into two groups, group 1:
      Hepatitis C patients with early viral response (EVR), group 2: Patients without
      EVR. Odds ratio (OR) and 95% confidence interval (CI) were calculated to assess
      the relationship between each risk factor and the EVR in both groups. RESULTS:
      During the study, 80 patients were analyzed, 45 retrospectively and 35
      prospectively. The mean +/- SD age of our subjects was 42.9 +/- 12 years; weight
      70 kg (+/- 11.19), AST 64.6 IU/mL (+/- 48.74), alanine aminotransferase (ALT)
      76.3 IU/mL (+/- 63.08) and platelets 209 000 mill/mm(3) (+/- 84 429). Fifty-five
      (68.8%) were genotype 1 and 25 (31.3%) were genotype 2 or 3; the mean hepatitis C
      virus RNA viral load was 2 269 061 IU/mL (+/- 7 220 266). In the univariate
      analysis, APRI was not associated with EVR [OR 0.61 (95% CI 0.229-1.655, P =
      0.33)], and the absence of EVR was only associated with genotype 1 [OR 0.28 (95%
      CI 0.08-0.94, P = 0.034)]. After adjustment in a logistic regression model,
      genotype 1 remains significant. CONCLUSION: APRI was not a predictor of EVR in
      chronic hepatitis C; Genotype 1 was the only predictive factor associated with
      the absence of EVR in our patients.

PMID- 19842224
TI  - Helicobacter pylori infection and gastropathy: a comparison between Indonesian
      and Japanese patients.
AB  - AIM: To compare the effects of Helicobacter pylori (H. pylori) infection on
      gastropathy between Indonesian and Japanese patients. METHODS: Biopsy specimens
      were obtained during upper gastrointestinal endoscopy from 167 subjects (125
      Indonesians and 42 Japanese) with uninvestigated symptoms of dyspepsia. The
      specimens were analyzed for the presence of H. pylori using urease analysis,
      histopathology, and cell culture. The grade and activity of gastritis was
      assessed using the updated Sydney system. RESULTS: The percentages of Indonesian
      and Japanese patients who were H. pylori-positive at the antrum or body of the
      stomach were similar (68% and 59.5%, respectively; P = 0.316). Of those who were
      H. pylori-positive, more Japanese patients than Indonesian patients had high
      levels of polymorphonuclear cells (P = 0.001), mononuclear cells (P = 0.013),
      glandular atrophy (P = 0.000), and intestinal metaplasia (P = 0.011) in both the
      antrum and body of the stomach. CONCLUSION: The grade of gastritis and prevalence
      of mucosal atrophy and intestinal metaplasia were higher in Japanese patients.
      The difference between Indonesian and Japanese patients was significant.

PMID- 19842225
TI  - Community-based cross-sectional seroprevalence study of hepatitis A in
      Bangladesh.
AB  - AIM: To elucidate the age-distribution of anti-hepatitis A virus (HAV)
      seroprevalence across different socioeconomic status (SES) categories in
      Bangladesh which, despite scarce data, is generally deemed to have high
      endemicity. METHODS: Blood samples of 818 subjects from a stratified sample of
      schools and hospitals, comprising different age categories and SES were
      collected. They were assayed for total anti-HAV antibodies. Social and medical
      history data were obtained using a questionnaire. RESULTS: Overall anti-HAV
      seroprevalence was 69.6%, increasing with age from 1-5 years (40.4%) to > 30
      years (98.4%). Seroprevalence was lowest (49.8%) in the high SES group and
      highest (96.5%) in the rural lower-middle SES group. Among subjects aged 6-20
      years, anti-HAV seroprevalence was lowest in urban private school children
      (43.0%), followed by urban government school children (76.2%) and rural school
      children (96.5%) (P < 0.01). Within the high SES group, anti-HAV seroprevalence
      was 32.3% in subjects < 10 years and 51.7% in those aged 11-20 years. Until now
      Bangladesh has been deemed to have high endemicity for HAV. CONCLUSION: The
      transition from high to intermediate HAV endemicity may be underway; high SES
      adolescents and adults remain particularly at risk of symptomatic illness.
      Preventive measures need consideration.

PMID- 19842226
TI  - Clinical outcomes in patients with ICU-related pancreatitis.
AB  - AIM: To identify risk factors predictive of intensive care unit (ICU) mortality
      in patients with ventilator-related pancreatitis. The clinical outcomes of
      patients with ventilator-related pancreatitis were compared with those of
      patients with pancreatitis-related respiratory failure as well as controls.
      METHODS: One hundred and forty-eight patients with respiratory failure requiring
      mechanical ventilation and concomitant acute pancreatitis were identified from a
      prospectively collected dataset of 9108 consecutive patients admitted with
      respiratory failure over a period of five years. Sixty patients met the criteria
      for ventilator-related pancreatitis, and 88 (control patients), for pancreatitis
      related respiratory failure. RESULTS: Mortality rate in ventilator-related
      pancreatitis was comparable to that in ICU patients without pancreatitis by case
      control methodology (P = 0.544). Multivariate logistic regression analysis
      identified low PaO(2)/FiO(2) (OR: 1.032, 95% CI: 1.006-1.059, P = 0.016) as an
      independent risk factor for mortality in patients with ventilator-related
      pancreatitis. The mortality rate in patients with ventilator-related pancreatitis
      was lower than that in patients with acute pancreatitis-related respiratory
      failure (P < 0.001). CONCLUSION: We found that low PaO(2)/FiO(2) was an
      independent clinical parameter predictive of ICU mortality in patients with
      ventilator-related pancreatitis.

PMID- 19842227
TI  - Study of glue extrusion after endoscopic N-butyl-2-cyanoacrylate injection on
      gastric variceal bleeding.
AB  - AIM: To investigate glue extrusion after endoscopic N-butyl-2-cyanoacrylate
      injection on gastric variceal bleeding and to evaluate the long-term efficacy and
      safety of this therapy. METHODS: A total of 148 cirrhotic patients in our
      hospital with esophagogastric variceal bleeding (EGVB) were included in this
      study. N-butyl-2-cyanoacrylate was mixed with lipiodol in a 1:1 ratio and
      injected as a bolus of 1-3 mL according to variceal size. Patients underwent
      endoscopic follow-up the next week, fourth week, second month, fourth month, and
      seventh month after injection and then every 6 mo to determine the cast shape. An
      abdominal X-ray film and ultrasound or computed tomographic scan were also
      carried out in order to evaluate the time of variceal disappearance and complete
      extrusion of the cast. The average follow-up time was 13.1 mo. RESULTS: The
      instantaneous hemostatic rate was 96.2%. Early re-bleeding after injection in 9
      cases (6.2%) was estimated from rejection of adhesive. Late re-bleeding occurred
      in 12 patients (8.1%) at 2-18 mo. The glue cast was extruded into the lumen
      within one month in 86.1% of patients and eliminated within one year. Light
      erosion was seen at the injection position and mucosa edema in the second week.
      The glue casts were extruded in 18 patients (12.1%) after one week and in 64
      patients (42.8%) after two weeks. All kinds of glue clumping shapes and colors on
      endoscopic examination were observed in 127 patients (86.1%) within one month,
      including punctiform, globular, pillar and variform. Forty one patients (27.9%)
      had glue extrusion after 3 mo and 28 patients (28.9%) after six months. The
      extrusion time was not related to the injection volume of histoacryl.
      Obliteration was seen in 70.2% (104 cases) endoscopically. The main complication
      was re-bleeding resulting from extrusion. The prognosis of the patients depended
      on the severity of the underlying liver disease. CONCLUSION: Endoscopic injection
      of cyanoacrylate is highly effective for gastric varices bleeding. The glue clump
      shape is correlated with anatomic structure of vessels. The time of extrusion was
      not related to dosage of the glue.

PMID- 19842228
TI  - Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma.
AB  - AIM: To investigate the inhibitory effects of genistein on metastasis of MHCC97-H
      hepatocellular carcinoma cells and to explore the underlying mechanism. METHODS:
      MHCC97-H hepatocellular carcinoma cells were exposed to genistein. A cell
      attachment assay was carried out in a microculture well pre-coated with
      fibronectin. The invasive activity of tumor cells was assayed in a transwell cell
      culture chamber, and cell cycle and apoptosis were evaluated by a functional
      assay. In addition, the expression and phosphorylation of FAK were detected by
      Western blotting. In situ xenograft transplantation of hepatocellular carcinoma
      was performed in 12 nude mice and lung metastasis of hepatocellular carcinoma was
      observed. RESULTS: Genistein significantly inhibited the growth of MHCC97-H cells
      in vitro. Adhesion and invasiveness of MHCC97-H cells were inhibited in a
      concentration-dependent fashion, and the inhibitory effect of genistein was more
      potent in the 10 microg/mL and 20 microg/mL genistein-treated groups. Genistein
      caused G(0)/G(1) cell cycle arrest, an S phase decrease, and increased apoptosis.
      The expression and phosphorylation of FAK in MHCC-97H cells were significantly
      decreased. In situ xenograft transplantation of hepatocellular carcinoma was also
      significantly suppressed by genistein. The number of pulmonary micrometastatic
      foci in the genistein group was significantly lower compared with the control
      group (12.3 +/- 1.8 vs 16.6 +/- 2.6, P < 0.05). CONCLUSION: Genistein appears to
      be a promising agent in the inhibition of metastasis of hepatocellular carcinoma.

PMID- 19842229
TI  - A new polymorphism in the GRP78 is not associated with HBV invasion.
AB  - AIM: To examine the association between -86 bp (T > A) in the glucose-regulated
      protein 78 gene (GRP78) and hepatitis B virus (HBV) invasion. METHODS: DNA was
      genotyped for the single-nucleotide polymorphism by polymerase chain reaction
      followed by sequencing in a sample of 382 unrelated HBV carriers and a total of
      350 sex- and age-matched healthy controls. Serological markers for HBV infection
      were determined by enzyme-linked immunosorbent assay kits or clinical chemistry
      testing. RESULTS: The distributions of allelotype and genotype in cases were not
      significantly different from those in controls. In addition, our findings
      suggested that neither alanine aminotransferase/hepatitis B e antigen nor HBV-DNA
      were associated with the allele/genotype variation in HBV infected individuals.
      CONCLUSION: -86 bp T > A polymorphism in GRP78 gene is not related to the
      clinical risk and acute exacerbation of HBV invasion.

PMID- 19842230
TI  - Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal
      carcinoma.
AB  - AIM: To investigate the role of neoadjuvant chemoradiotherapy in prognosis and
      surgery for esophageal carcinoma by a meta-analysis. METHODS: PubMed and manual
      searches were done to identify all published randomized controlled trials (RCTs)
      that compared neoadjuvant chemoradiotherapy plus surgery (CRTS) with surgery
      alone (S) for esophageal cancer. According to the test of heterogeneity, a fixed
      effect model or a random effect model was used and the odds ratio (OR) was the
      principal measure of effects. RESULTS: Fourteen RCTs that included 1737 patients
      were selected with quality assessment ranging from A to C (Cochrane Reviewers'
      Handbook 4.2.2). OR (95% CI, P value), expressed as CRTS vs S (values > 1 favor
      CRTS arm), was 1.19 (0.94-1.48, P = 0.28) for 1-year survival, 1.33 (1.07-1.65, P
      = 0.69) for 2-year survival, 1.76 (1.42-2.19, P = 0.11) for 3-year survival, 1.41
      (1.06-1.87, P = 0.11) for 4-year survival, 1.64 (1.28-2.12, P = 0.40) for 5-year
      survival, 0.82 (0.39-1.73, P < 0.0001) for rate of resection, 1.53 (1.33-2.84, P
      = 0.007) for rate of complete resection, 1.78 (1.14-2.78, P = 0.79) for operative
      mortality, 1.12 (0.89-2.48, P = 0.503) for all treatment mortality, 1.33 (0.94
      1.88, P = 0.04) for the rate of adverse treatment, 1.38 (1.23-1.63, P = 0.0002)
      for local-regional cancer recurrence, 1.28 (0.85-1.58, P = 0.60) for distant
      cancer recurrence, and 1.27 (0.86-1.65, P = 0.19) for all cancer recurrence. A
      complete pathological response to chemoradiotherapy occurred in 10%-45.5% of
      patients. The 5-year survival benefit was most pronounced when chemotherapy and
      radiotherapy were given concurrently (OR: 1.45, 95% CI: 1.26-1.79, P = 0.015)
      instead of sequentially (OR: 0.85, 95% CI: 0.64-1.35, P = 0.26). CONCLUSION:
      Compared with surgery alone, neoadjuvant chemoradiotherapy can improve the long
      term survival and reduce local-regional cancer recurrence. Concurrent
      administration of neoadjuvant chemoradiotherapy was superior to sequential
      chemoradiotherapy.

PMID- 19842231
TI  - Management of venous stenosis in living donor liver transplant recipients.
AB  - AIM: To retrospectively evaluate the management and outcome of venous obstruction
      after living donor liver transplantation (LDLT). METHODS: From February 1999 to
      May 2009, 1 intraoperative hepatic vein (HV) tension induced HV obstruction and 5
      postoperative HV anastomotic stenosis occurred in 6 adult male LDLT recipients.
      Postoperative portal vein (PV) anastomotic stenosis occurred in 1 pediatric left
      lobe LDLT. Patients ranged in age from 9 to 56 years (median, 44 years). An air
      balloon was used to correct the intraoperative HV tension. Emergent surgical
      reoperation, transjugular HV balloon dilatation with stent placement and
      transfemoral venous HV balloon dilatation was performed for HV stenosis on days
      3, 15, 50, 55, and 270 after LDLT, respectively. Balloon dilatation followed with
      stent placement via superior mesenteric vein was performed for the pediatric PV
      stenosis 168 d after LDLT. RESULTS: The intraoperative HV tension was corrected
      with an air balloon. The recipient who underwent emergent reoperation for hepatic
      stenosis died of hemorrhagic shock and renal failure 2 d later. HV balloon
      dilatation via the transjugular and transfemoral venous approach was technically
      successful in all patients. The patient with early-onset HV stenosis receiving
      transjugular balloon dilatation and stent placement on the 15th postoperative day
      left hospital 1 wk later and disappeared, while the patient receiving the same
      interventional procedures on the 50th postoperative day died of graft failure and
      renal failure 2 wk later. Two patients with late-onset HV stenosis receiving
      balloon dilatation have survived for 8 and 4 mo without recurrent stenosis and
      ascites, respectively. Balloon dilatation and stent placement via the superior
      mesenteric venous approach was technically successful in the pediatric left lobe
      LDLT, and this patient has survived for 9 mo without recurrent PV stenosis and
      ascites. CONCLUSION: Intraoperative balloon placement, emergent reoperation,
      proper interventional balloon dilatation and stent placement can be effective as
      a way to manage hepatic and PV stenosis during and after LDLT.

PMID- 19842232
TI  - Forgotten node: a case report.
AB  - Sister Mary Joseph nodule or node refers to a palpable nodule bulging into the
      umbilicus and is usually a result of a malignant cancer in the pelvis or abdomen.
      Traditionally it has been considered a sign of ominous prognosis.
      Gastrointestinal malignancies, most commonly gastric, colon and pancreatic cancer
      account for about 52% of the underlying sources. Gynecological cancers, most
      commonly ovarian and uterine cancers account for about 28% of the sources.

PMID- 19842233
TI  - Muscularis mucosae in desmoplastic stroma formation of early invasive rectal
      adenocarcinoma.
AB  - The origin of myofibroblasts or myofibroblastic cells in the desmoplastic stroma
      associated with carcinoma invasion has been controversial. In the early invasive
      area of a rectal adenocarcinoma reported here, an obvious transition between the
      muscularis mucosa and the bundles of eosinophilic stromal cells observed in the
      carcinomatous stroma was demonstrated both in morphology and in their
      cytoskeletal phenotype, which conceivably suggests that the smooth muscle cells
      of the muscularis mucosa could convert to the eosinophilic stromal cells, namely
      myofibroblasts. Moreover, type I procollagen was demonstrated in both protein and
      mRNA levels in the areas of eosinophilic stromal cells with a lesser degree of
      differentiated smooth muscle phenotype that showed a transition from the
      muscularis mucosa, implying that the myofibroblastic cells converted from smooth
      muscle cells of the muscularis mucosa could be responsible for type I collagen
      production. These findings suggest that the muscularis mucosae may not be a
      passive barrier through which colorectal carcinomas infiltrate into the
      submucosa, but may play an active role in the formation and remodeling of tumor
      stroma.

PMID- 19842234
TI  - Cystic Brunner's gland hamartoma in the duodenum: a case report.
AB  - Cystic Brunner's gland hamartoma in the duodenum is exceedingly rare, although
      microscopic examination may sometimes reveal a Brunner's gland hamartoma
      containing dilated ducts in the duodenum. We present a case of large cystic
      Brunner's gland hamartoma in the duodenum with a long stalk, which is described
      in light of multidetector-row computed tomography, magnetic resonance imaging,
      and a modified small bowel series, together with pathologic correlation and
      differential diagnosis.

PMID- 19842235
TI  - Travel of a mis-swallowed long spoon to the jejunum.
AB  - Foreign-body ingestion is a relatively common presentation at emergency
      departments, but long metallic spoon swallowing is an infrequent occurrence.
      Unlike most cases of foreign-body ingestion, there have been no reported cases of
      long foreign bodies reaching the jejunum. We report a rare case of a coffee spoon
      that was swallowed accidentally and passed through the pylorus and duodenal loop
      and reached the jejunum, with no complications.

PMID- 19842236
TI  - Controversies about occult hepatitis B virus infection.
AB  - We read with great interest the paper written by Shi et al, reviewing the
      molecular characteristics and stages of chronic hepatitis B virus (HBV)
      infection. We think that some points in the definition of occult HBV infection
      (OBI) and their conclusion about the management of OBI may need further
      considerations.

PMID- 19842237
TI  - Developing new guidelines for the diagnosis  and treatment of pulmonary
      hypertension.
AB  - Jennifer Taylor MPhil, talks to Nazzareno Galie , FESC, FRCP, chairman of the
      committee for the 2009 guidelines. What's new, changes from previous
      recommendations, which decisions were difficult, what they mean and should do.

PMID- 19842239
TI  - How relevant is dietary fish consumption to the low myocardial infarction rates
      in Japan?

PMID- 19842242
TI  - A comparison between target-controlled and manually controlled propofol infusions
      in patients undergoing routine surgical procedures.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have shown that target-controlled
      infusion (TCI) was associated with increased propofol consumption as compared
      with manually controlled infusion (MCI). However, most studies lacked an
      objective measurement of anaesthetic depth. We compared TCI and MCI with regard
      to propofol dose requirement while monitoring depth of anaesthesia with
      bispectral index (BIS) and midlatency auditory-evoked potentials (MLAEPs).
      METHODS: Fifty ASA 1 or 2 patients undergoing elective ENT surgery were randomly
      allocated to the TCI group (n = 25)or the MCI group (n = 25). BIS, MLAEPs,
      haemodynamic parameters and propofol plasma concentration were determined at
      various stages before, during and after anaesthesia. During anaesthesia, BIS
      values were always maintained between 40 and 60. RESULTS: Anaesthesia
      significantly increased latency of Pa and Nb compared with when patients were
      awake (P < 0.01). After extubation, the latency of Pa and Nb significantly
      decreased and basically returned to baseline level. BIS and latency of both Pa
      and Nb did not differ between groups.Also, the propofol induction dose (mean WSD:
      TCI, 2.09 +/- 0.36 mg kg(-1); MCI, 2.06 +/- 0.16 mg kg(-1) and total dose (TCI,
      5.57 +/- 0.96 mg kg(-1) h(-1); MCI, 5.79 +/- 0.87 mg kg(-1) h(-1) and measured
      plasma propofol concentration during anaesthesia did not differ between groups.
      At 15 min after intubation, the mean predicted plasma concentration (2.2 +/- 0.2
      microg ml(-1)) differed significantly from the measured plasma concentration (2.8
      +/- 1.2 microg ml(-1)). No correlation was observed between predicted and
      measured propofol plasma concentrations.

PMID- 19842243
TI  - Haemodynamic effects during endoscopic vein harvest of the saphenous vein for off
      pump coronary artery bypass grafting surgery.
AB  - OBJECTIVE: Endoscopic vein harvest (EVH) for coronary artery bypass grafting
      surgery is performed with carbon dioxide (CO2) insufflation for visualization and
      dissection. The insufflated CO2 is rapidly absorbed into the body and may
      influence haemodynamics. However, the haemodynamic changes during EVH have not
      been clearly defined. This study evaluated the haemodynamic effects during EVH of
      the saphenous vein for off-pump coronary artery bypass grafting surgery (OPCAB).
      METHODS: After fixing the position for harvesting of the left internal mammary
      artery, EVH of the saphenous vein was performed at a maximum CO2 pressure of 12
      mmHg and a flow of 3 l/min. The haemodynamic parameters were measured before and
      just after the end of endoscopic vein harvest. RESULTS: One hundred patients were
      studied. The end-tidal CO2 pressure (P(ET)CO2, 35.0 +/- 2.7 vs. 52.0 +/- 6.2
      mmHg), partial pressure of arterial CO2 (PaCO2, 35.1 +/- 3.1 vs. 52.5 +/- 4.3
      mmHg), mixed venous oxygen saturation (SvO2, 75.6 +/- 4.1 vs. 82.0 +/- 1.6%),
      cardiac index (2.7 +/- 0.6 vs. 3.3 +/- 0.6 l/min/m2), and cerebral oxygen
      saturation (ScO2, left: 63.5 +/- 7.9 vs. 73.3 +/- 8.4; right: 62.2 +/- 8.0 vs.
      72.3 +/- 6.3%) differed significantly between before and after CO2 insufflation,
      whereas mean systemic blood pressure, mean pulmonary artery blood pressure,
      central venous pressure, heart rate, partial pressure of arterial oxygen, and
      peak inspiratory pressure did not differ significantly between before and after
      CO2 insufflation. CONCLUSIONS: EVH, at a maximum CO2 pressure of 12 mmHg and a
      flow of 3 l/min, of the saphenous vein for OPCAB was associated with hypercarbia
      and a tolerable range of hypercarbia (PaCO2 < 60 mmHg) increased the cardiac
      index and ScO2 without any complications.

PMID- 19842244
TI  - Interactive medical case. A bloody mystery.

PMID- 19842245
TI  - Lung-cancer staging with PET-CT.

PMID- 19842246
TI  - Lung-cancer staging with PET-CT.

PMID- 19842247
TI  - Lung-cancer staging with PET-CT.

PMID- 19842248
TI  - Lung-cancer staging with PET-CT.

PMID- 19842249
TI  - Capsule endoscopy versus colonoscopy.

PMID- 19842250
TI  - A useful reconstruction arrangement following Whipple's resection for patients
      with familial adenomatous polyposis.

PMID- 19842251
TI  - Rapid splintage of acute long-bone fractures.

PMID- 19842252
TI  - Enterocutaneous fistula stent.

PMID- 19842253
TI  - A handy hint in using an image intensifier  during wrist and hand surgery.

PMID- 19842254
TI  - The cut-down 1-ml syringe--an excellent  improvised drill sleeve.

PMID- 19842255
TI  - The use of non-adhesive skin traction to prevent  distal migration of a cylinder
      cast.

PMID- 19842256
TI  - Accurate injection of small joints--a useful  technique.

PMID- 19842257
TI  - A modified switching stick technique to  facilitate portal access in elbow
      arthroscopy.

PMID- 19842258
TI  - The barrel and cuff technique for a bloodless  field.

PMID- 19842259
TI  - Giving microbial diversity a home.

PMID- 19842260
TI  - In case of emergency ... ... IOM seeks tougher clinician legal protections.

PMID- 19842261
TI  - Messy problem.
AB  - Tougher EPA rules on incinerating medical waste have hospitals grappling with how
      to manage their garbage. Outsourcing is one possibility, but that will involve
      higher costs, too. "There will be cost, but it will be nominal. We think it will
      be less than 5% of current operating costs," says Steven Groenke, vice president
      of medical-waste processor Curtis Bay Energy.

PMID- 19842262
TI  - The numbers game. DSH payments, uninsured counts roil Senate.

PMID- 19842263
TI  - Medicare melee. Humana ordered to halt 'scare tactic' mailings.

PMID- 19842264
TI  - Rethinking the rules. FTC, Justice may rewrite guidelines on mergers.

PMID- 19842265
TI  - Meaningful marketing. Vendors say products will meet unknown guidelines.

PMID- 19842266
TI  - Dell's HIT power play. Experts ponder ramifications of proposed Perot deal.

PMID- 19842267
TI  - Tenet's debt strategy. Chain sells $345 million of convertible stock.

PMID- 19842268
TI  - Doing a number on the uninsured. Whatever the figure, it's too high and cries out
      for some solutions.

PMID- 19842269
TI  - Get on the same page. Radiologists need collegiality, humility--not arrogance to
      survive.

PMID- 19842270
TI  - Finding a niche. More outsourcing focuses on narrower services such as
      technology, revenue cycle rather than the end-to-end approach.

PMID- 19842271
TI  - Parliament set to battle over Monitor and autonomy of foundation trusts.

PMID- 19842272
TI  - GP flu jab deal fails to please all contractors.

PMID- 19842273
TI  - Incentive paradox dogs weight loss procedures.

PMID- 19842274
TI  - On labour's mistakes.

PMID- 19842275
TI  - Don't steer by the rear view mirror.

PMID- 19842276
TI  - Patient safety. Oops! I did it again.

PMID- 19842277
TI  - Finance. Getting to grips retainers.

PMID- 19842278
TI  - Human resources. The keys to unlock leadership.

PMID- 19842279
TI  - Legal. What about the workers?

PMID- 19842280
TI  - Commentary.

PMID- 19842281
TI  - The disposition of hepatitis C antibody-positive patients in an urban hospital.
AB  - Previous studies have indicated that only 26-61% of hepatitis C virus (HCV)
      antibody-positive patients are referred to specialists who treat HCV. However,
      these studies were conducted in homogeneous populations and before pegylated
      interferon and ribavirin became the standard of care for chronic HCV infection.
      The aims of this study were: (i) to determine the percentage of HCV antibody
      positive patients who were referred to specialists for further management in an
      urban, racially diverse population, (ii) to determine the percentage of referred
      patients who attend specialty clinics, and (iii) to identify factors that predict
      referral and follow-up. All patients with a positive HCV antibody test in 2005
      were identified by an inquiry of Epic, our electronic medical record system. All
      medical records were reviewed for demographics, location where the test was
      ordered (inpatient vs outpatient), specialty ordering the test, referral, clinic
      attendance, detectability of HCV RNA and liver function tests. Univariate and
      multivariate logistic regression were used to evaluate each variable's effect on
      referral and clinic attendance. Overall, 251 of 375 (67%) antibody positive
      patients were referred to HCV specialists. Of the 251 referrals, 166 (66%)
      attended at least one specialty clinic appointment. Patients were more likely to
      be referred if their HCV antibody was ordered in the outpatient setting (77%
      outpatient vs 38% inpatient, P < 0.001) ordered by a family practitioner (79% FP
      vs 64% for internal medicine doctor vs 58% for all other specialties, P = 0.01)
      had detectable RNA (88% detectable vs 65% not detectable vs 23% RNA status not
      available, P < 0.001) or elevation of alanine aminotransferase (75% elevated vs
      56% not elevated, P < 0.001). Location, HCV RNA status and ALT elevation remained
      significant in a multivariate logistic regression model. These data confirm that
      up to one-third of HCV antibody-positive patients are not referred to HCV
      specialists, despite the availability of improved treatment regimens. Additional
      patients are lost to follow-up after being referred. The reasons for suboptimal
      referral and specialty clinic attendance rates are probably multifactorial.
      Institution of reflexive RNA testing for positive antibody tests and additional
      education of those physicians who encounter HCV-positive individuals may improve
      both rates.

PMID- 19842282
TI  - Evaluation the current role of Nigerian medical schools in the training of
      medical graduates.
AB  - Medical schools in Nigeria, called synonymously as College of Medicine, College
      of Health Sciences or simply Faculty of Medicine, are those institutions charged
      by law with the responsibility of training and graduating medical doctors. Since
      the early days of the establishment of the faculty of medicine in Ibadan as an
      arm of the University of London, in 1948, Nigeria has come a long way. This paper
      sought to examine the various stages medical education had gone through in the
      country, to highlight problems and prospects and to challenge medical educators
      to chart a way forward for the sector.

PMID- 19842283
TI  - Post-graduate medical education in Nigeria - an overview.

PMID- 19842284
TI  - Funding medical education in Nigeria: existing constraints and an insight into
      practicable remedies.

PMID- 19842286
TI  - Newthink.

PMID- 19842285
TI  - Continuing professional development for medical practitioners - the way forward.

PMID- 19842287
TI  - [Geodemography of the Rhone department from the 1911 census].

PMID- 19842288
TI  - [Portrait of a group: the middle classes and public housing in interwar Paris].

PMID- 19842289
TI  - [Rendering justice in a rural community under the ancien regime: Grignan and the
      Bertholon affair in 1702].

PMID- 19842290
TI  - [The occupational arrangements of refugees from Asia Minor in Greek urban areas,
      1922-1930].

PMID- 19842291
TI  - Christopher Merrett's "Pinax rerum naturalium britannicarum" (1666): annotations
      to what is believed to be the author's personal copy.
AB  - In 1666, Christopher Merrett published "Pinax rerum naturalium britannicarum,"
      this essentially being a catalogue of British plant localities known at the time
      together with a few other items of natural history. What is thought to be the
      author's personal annotated copy is held in the British Library. These
      annotations have been examined and the hand-writing compared to surviving
      examples known to be either of the author or of one of his sons and are now
      transcribed. Brief biographical notes relating to Merrett and to the background
      to his production of the "Pinax" are also given.

PMID- 19842292
TI  - The bibliography of Robert Edmond Grant (1793-1874): illustrated with a
      previously unpublished photograph.
AB  - The comparative anatomist Robert Edmond Grant (1793-1874), best known for his
      work on sponges and other marine invertebrates, was important as a teacher and
      outspoken as a medical reformer. At Edinburgh University his transformist zoology
      provided the young Charles Darwin with his first theoretical framework. As
      professor of Zoology and Comparative Anatomy at the newly founded University of
      London, Grant influenced a new generation of comparative anatomists and medical
      men, even if his radical science and calls for reform in medical and scientific
      society made him unpopular with the conservative elite which held sway. In spite
      of his pivotal position, very little is known about the man. Here we present the
      most complete bibliography to date, consisting of 128 entries. This list also
      includes a breakdown of his published lectures.

PMID- 19842293
TI  - Drawings for an exacting author: illustrations from Giovanni Antonio Scopoli's
      "Deliciae florae et faunae insubricae".
AB  - Giovanni Antonio Scopoli (1723-1788) was one of the most versatile naturalists in
      eighteenth-century Italy. In 1785, Scopoli conceived the ambitious publication,
      "Deliciae florae et faunae insubricae". Appearing in installments, this included
      descriptions and illustrations of plants, animals and minerals found in northern
      Italy. Unfortunately, Scopoli's sudden death halted publication of the "Deliciae"
      after its third installment. Recently, a corpus of 98 paintings, in the gouache
      style, were discovered in the Biblioteca Universitaria of Pavia. These gouaches
      appear to be the basis for plates planned in future installments of the
      "Deliciae". Marginal notes in Scopoli's handwriting are included. Because
      Scopoli's plant and animal specimens have been destroyed or dispersed, these
      drawings are crucial for reconstructing his scientific opus. Combined with other
      documents, Scopoli's marginal notes also reveal his exacting standards. He
      criticized the way his artists had poorly rendered the scientific details of the
      paintings.

PMID- 19842294
TI  - African Americans in commercial HMOs more likely to delay prescription drugs and
      use the emergency room.
AB  - Health Maintenance Organizations (HMOs) are designed to provide comprehensive
      health care, including primary care to their enrollees. However, HMOs deliver
      care through a wide variety of physician networks, settings and methods
      throughout the nation and in California. Minorities and individuals of lower
      socioeconomic status continue to disproportionately rely on the health care
      safety net, even when insured. Individuals enrolled in HMOs should be less likely
      to rely on emergency rooms and experience ambulatory care sensitive
      hospitalizations given the focus of HMOs on centralized care through the use of a
      primary care provider. This policy brief uses data from the 2007 California
      Health Interview Survey (CHIS 2007) to examine delays in fulfilling prescribed
      medications, delays in obtaining needed medical care, visits to emergency rooms,
      and the presence of a usual source of care among insured African Americans in
      public and commercial HMOs. We find that African-American HMO enrollees in
      California are more likely to delay obtaining needed medications and use the
      emergency room than other racial/ethnic groups in comparable HMO plans.

PMID- 19842295
TI  - Re: "Lip posture following debonding of labial appliances based on conventional
      profile photographs".

PMID- 19842296
TI  - Re: "Analysis of orthodontically induced root resorption using micro-computed
      tomography (Micro-CT)".

PMID- 19842297
TI  - Introduction: "The everything issue".

PMID- 19842298
TI  - The normalisation of substance abuse among young travellers in Ireland:
      implications for practice.
AB  - This report presents the findings of an exploratory study aimed at assessing the
      nature and extent of drug use amongst a group of young Travellers (aged twelve to
      eighteen years) in the South Eastern Region of Ireland. The results are intended
      to inform the Irish policy debate by providing data on patterns of youth drug
      use, drug-related risk behaviours, the impact of drug use on the Traveller
      community and issues regarding access to services. The young Travellers exhibited
      similar trends to "settled" adolescents with regard to drug use trends and
      attitudes but reported poor levels of health awareness and knowledge of drug
      services. The social exclusion of young Travellers puts them at risk of
      problematic drug use due to issues of poor literacy levels, family crisis,
      discrimination, poor knowledge of service provision relating to drug education
      and treatment, and the location of halting sites in areas of high drug usage.

PMID- 19842299
TI  - Multiple drug use and polydrug use amongst homeless traveling youth.
AB  - Diverse forms of drug use are an emerging theme within research on young people
      and substance use. This manuscript, based on a three city study of health risks
      amongst young injection drug users, explores multiple drug use and polydrug use
      amongst a subset of homeless youth referred to as "travelers." In particular, we
      outline characteristics of homeless traveler youths and the various ways in which
      they practiced multiple drug use and polydrug use. From here, we discuss some
      theoretical and public health implications of multiple drug use and polydrug use
      amongst this particular population.

PMID- 19842300
TI  - Latino gay men's drug functionality: the role of social networks and social
      support.
AB  - This study describes the consequences of drug use and abuse across Latino gay
      men's (LGM) lives. We also explore the role social networks play in LGM's access
      to drug use, as well as identifying the role of social support in regulating drug
      intake. Using a thematic content analysis, we analyzed a subsample (n = 16) of
      the interviews. Results suggest LGM's drug functionality varies according to
      their involvement in non-drug and drug-present social networks, with functional
      drug users reporting less convergence of their social networks than their drug
      abusing counterparts. Furthermore, participants voiced being able to regulate
      their drug intake better when social support was available in their networks.
      These findings suggest the importance of developing preventative and harm
      reduction programs with strong social networks and social support components.

PMID- 19842301
TI  - Evaluation of a residential Kundalini yoga lifestyle pilot program for addiction
      in India.
AB  - Previously reported substance abuse interventions incorporating meditation and
      spiritual approaches are believed to provide their benefit through modulation of
      both psychological and pyschosocial factors. A 90-day residential group pilot
      treatment program for substance abuse that incorporated a comprehensive array of
      yoga, meditation, spiritual and mind-body techniques was conducted in Amritsar,
      India. Subjects showed improvements on a number of psychological self-report
      questionnaires including the Behavior and Symptom Identification Scale and the
      Quality of Recovery Index. Application of comprehensive spiritual lifestyle
      interventions may prove effective in treating substance abuse, particularly in
      populations receptive to such approaches.

PMID- 19842302
TI  - Risk and protective factors for binge drinking among Hispanic subgroups in
      Florida.
AB  - This study examines differences in risk and protective factors for binge drinking
      among six ethnic/national subgroups of Hispanic adolescents in Florida. We note
      differences in the frequency of binge drinking by gender and ethnic subgroup as
      well as differences in the salience of items drawn from the five domains of risk
      and protective factors among these subgroups. Rather than treating all Hispanics
      as a unitary culture, tailoring of prevention programs to address risk and
      protective factors that differentially affect national/ethnic subgroups may be a
      valuable strategy when adolescents live in communities that are relatively
      homogenous in terms of nationality/ethnicity.

PMID- 19842303
TI  - The race/ethnic age crossover effect in drug use and heavy drinking.
AB  - Existing literature suggests that Blacks and to some extent Hispanics are less
      likely than Whites to use substances in their youth. However, by age 35 their use
      rates are higher than those of Whites. This has been referred to as the
      race/ethnic age crossover effect in substance use. However, more research is
      needed to clarify whether this is true for Blacks and Hispanics, males and
      females, and for drugs and alcohol. It is also empirically unclear why this
      crossover effect occurs. The present study explores these issues. The National
      Household Survey of Drug Abuse is merged for four years (1999-2002) to study the
      race/ethnic age crossover effect (n = 208,878). The results suggest that the
      race/ethnic age crossover effect cannot be used to describe Hispanic relative to
      White substance use. However, it is applicable to Black substance use, in
      particular illegal drug use for Black males and heavy drinking for Black females.
      Additional analyses reveal that the crossover effect for Blacks is eliminated
      when socio-demographic controls are included. With controls, drug use and heavy
      drinking for Blacks are lower than that of Whites for all age groups and for both
      males and females. Process differences are also revealed in the effects of the
      socio-demographic correlates. More specifically, these analyses of composition
      and process suggest that drug availability/exposure is a particularly important
      factor which likely contributes to the crossover effect in substance use and
      deserves further study.

PMID- 19842304
TI  - Perceptions of HIV risk behaviors and service needs among methamphetamine users
      in rural Appalachian Tennessee.
AB  - Like many areas of the country, the state of Tennessee is experiencing a recent
      and growing rise in the rate of methamphetamine use, particularly in rural areas
      of the state. While substance use is a known risk factor for contracting
      HIV/AIDS, there is limited information regarding the risk behaviors of rural
      methamphetamine users. This paper seeks to document the existence of known HIV
      risk behaviors as they relate to rural southern methamphetamine use. Qualitative
      interviews with ninety-seven current and former methamphetamine users from the
      Cumberland Plateau area, a rural mountainous region in the state of Tennessee,
      suggest that methamphetamine users are putting themselves at risk for contracting
      HIV/AIDS and other blood-borne diseases through high-risk injection and sexual
      behaviors. Additionally, the results present the perceptions of respondents
      regarding the impact of methamphetamine use on rural communities and related
      service needs.

PMID- 19842305
TI  - Introduction: tobacco and ethnicity.

PMID- 19842306
TI  - A cross-cultural and historical survey of tobacco use among various ethnic
      groups.
AB  - This review of tobacco use in diverse historical and cultural contexts reveals a
      range of behaviors engaged in and perspectives held by members of respective
      ethnic groups, such as whether to consider tobacco as a medicine or as a problem.
      After its introduction to Western societies, many attributed tobacco with an
      array of medicinal uses, while condemning recreational use and identifying it as
      immoral. Tobacco has been used variously by respective ethnic groups at different
      times and places and these customs have flavored understandings of the
      relationships between tobacco and the body. Considerable ethnic variation exists
      not only in terms of tobacco use and abuse, but also with respect to
      pharmacogenetic factors that influences the consequences of tobacco exposure.
      There have also been different societal responses to the use of tobacco,
      including those related to the media, as well as to issues of treatment and
      prevention.

PMID- 19842307
TI  - Black 'N Mild and carcinogenic: cigar smoking among inner city young adults in
      Hartford, CT.
AB  - Considerable concern has been expressed about the use of illicit drugs like
      heroin and cocaine among disadvantaged, minority youth and young adults in
      America's inner cities. Often overlooked in this research and associated public
      response are the far greater health consequences that stem from the use of
      legally sold drugs like alcohol and tobacco (Baer, Singer, and Susser, 2003,
      Singer, 2004). Recently, based on research in Miami/Dade and Alachua, Florida,
      Page and Evans (2003) have drawn attention to the significant rise in small
      cigars use among urban youth, especially African Americans between 11 and 15
      years of age. They note that "a cigarillo called 'Black 'N Mild' that contains
      between five and twelve times the nicotine of cigarettes has become the product
      of choice among African American and other youth" in the counties under study
      (Page and Evans, 2003:64). To date, there has been only limited research on the
      existence of this practice among inner city youth and young adults in other
      locales (Malone, Yerger, & Pearson, 2001). This paper reports on findings on
      Black 'N Mild use from a study of changing licit and illicit drug use among inner
      city populations in Hartford, CT; these findings include similarities to and
      differences from the findings reported by Page and Evans. The study highlights
      the importance of examining regional differences in drug use patterns (Singer et
      al., 1992).

PMID- 19842308
TI  - Toward an explanation of observed ethnic differences in youths' tobacco use.
AB  - We examined whether differences in smoking rates of Asian and white/Caucasian
      youth could be explained by personal (gender, employment status, volunteerism,
      parental education, and income) and social factors including differences in
      youths' relationships with their parents, extent of enculturation, and exposure
      to parental or peer smoking. A survey was conducted of a random sample of schools
      in 2 cities in British Columbia, Canada to obtain data from 3,278 high school
      students. Results from logistic regression analysis indicated smoking status was
      explained by place of birth, volunteerism, amount of income received from parents
      and employers, characteristics of the parental-child relationship, and parental
      and peer smoking status. Differences in the estimated risks of smoking of Asian
      youth and white youth were moderated by the youths' willingness to tell their
      parents about their lives, whether they worked for pay, and whether the Asian
      youth spoke English at home.

PMID- 19842309
TI  - Tobacco use and dependence in Asian American and Pacific Islander adolescents: a
      review of the literature.
AB  - PURPOSE: This article identifies gaps in extant tobacco literature and areas for
      further research on Asian American adolescents. METHODS: Research articles
      published until December 2005 were retrieved from computer-database and manual
      searches. RESULTS: A total of 62 data based research articles were identified and
      most (N= 38, 61.3%) had been published within the past 5 years. Chinese,
      Filipino, and Japanese American adolescents were studied most frequently. In
      general, Asian-American adolescents initiated smoking later and had a lower
      prevalence rate than non-Asian American adolescents. However, the estimates of
      current smoking for Native Hawaiian, Pacific Islander, and Filipino American
      adolescents in Hawaii were higher than those for adolescents in any other racial
      and ethnic groups. Most risk factors for smoking initiation were found to be
      similar to other ethnic minority groups, including the positive association of
      smoking with acculturation. For this age group the three treatment studies
      evaluated culturally focused interventions, but did not find improved outcomes.
      CONCLUSION: Further research is needed to identify factors associated with the
      growing use of cigarettes and other tobacco products in late adolescence and
      young adulthood within the population, including treatment outcome studies.
      Research recommendations are suggested.

PMID- 19842310
TI  - Regular tobacco use among American Indian and Alaska native adolescents: an
      examination of protective mechanisms.
AB  - American Indian and Alaska Native (AIAN) adolescents use tobacco at earlier ages
      and in larger quantities compared to non-AIAN peers. Regular tobacco use was
      examined against five protective factors (peer networks supportive of not using
      drugs, college aspirations, team sports, playing music, and volunteerism).
      Participants consisted of 112 adolescents between the ages of 13 and 19 who
      participated in a study testing the efficacy of a life-skills program aimed at
      reducing substance-related consequences. Findings indicated that, with the
      exception of prosocial peer networks and volunteerism, each of the above factors
      was significantly associated with a reduced probability of being a regular
      tobacco user. Gender differences were notable. These results hold important
      treatment implications regarding the reduction and prevention of tobacco use
      among AIAN youth.

PMID- 19842311
TI  - Association between tobacco use and lifestyle in a sample of lower income urban
      African-Americans in the American south.
AB  - There has been little research evaluating links between low-income populations'
      lifestyles and their tobacco use status. We surveyed 398 low-income individuals
      living in Housing Authority complexes in Columbus, Georgia. Current, former, and
      never tobacco users were compared for their health-related behaviors and
      lifestyles. Study findings suggest that current tobacco users were less healthy
      than comparisons, but had less unfavorable obesity measurements. In lifestyle
      choices, tobacco users were more likely than comparisons to be interested in
      sports (football, basketball, etc.), shopping, and participate in church
      activities.

PMID- 19842312
TI  - Smoking susceptibility and attitudes toward smoking among Chinese and Vietnamese
      American adolescents.
AB  - In California, 641 Chinese and 629 Vietnamese age 12-17 participated in a
      longitudinal telephone study from 1999 to 2001. Four attitude scales were
      constructed: acceptance of smokers, addictive nature of smoking, psychosocial
      reasons to smoke, and gender roles and smoking. Vietnamese American adolescents
      had more pro-smoking attitudes than Chinese American adolescents. Male gender,
      having friends who smoked, and baseline smoking were associated with smoking
      susceptibility at follow-up. Those factors, U.S. birthplace, and the acceptance
      and psychosocial scales were associated with smoking. Smoking prevention efforts
      targeting Chinese and Vietnamese American adolescents should focus on gender,
      birthplace, peer smoking, and attitudes.

PMID- 19842313
TI  - Incest and parental contact: a psychologist' s personal case and literature
      review.
AB  - A psychologist's husband molested their young daughter. Consulting psychologists
      purported that research indicated it would be developmentally advantageous for
      their daughter to continue a relationship with the father following the marital
      separation. The consulting psychologists did not reference the literature,
      prompting the mother to conduct a literature review herself. The available
      literature recommending that a child continue the paternal relationship cites
      research on children of divorce, not research on the treatment of child sex abuse
      victims. The scant child sex abuse research that addresses contact with the
      abusing parent actually indicates more harm than benefit occurs to the child.

PMID- 19842314
TI  - Consider the source: a commentary on incest and parental contact.

PMID- 19842315
TI  - Therapeutically managing reunification after abuse allegations.

PMID- 19842316
TI  - Does psychotherapy recover or invent child sexual abuse memories? A case history.
AB  - ABSTRACT. This case describes bodily experiences that appeared to cue child
      sexual abuse memories during psychotherapy by a woman who was amnesic for her
      childhood and suffered from chronic dissociative states. Though corroboration was
      unavailable, she became increasingly confident about her returning memories.
      Special efforts were made to avoid making suggestions. The article proposes the
      theory that integrates the construct of the self with the relationship between
      bodily experiences and memory narratives. It suggests that: (1) amnesia and
      recovering memories involve normal and abnormal memory mechanisms; (2)
      remembering during psychotherapy is complex; (3) psychotherapy need not be
      suggestive; (4) inaccessible memories may act as constraints on suggestibility;
      and (5) narrative recall may depend on the connection of bodily experiences with
      self-reflection.

PMID- 19842317
TI  - The convergent validity of the trauma symptom checklist for young children for a
      sample of sexually abused outpatients.
AB  - The convergent validity of the Trauma Symptom Checklist for Young Children
      (TSCYC) was examined with a sample of 172 sexually abused outpatient treatment
      seeking children and their caregivers. The TSCYC evidenced good convergent
      validity with other parent ratings (e.g., the Child Behavior Checklist, Child
      Sexual Behavior Inventory, and the University of California at Los Angeles Post
      Traumatic Stress Disorder Reaction Index [UCLA PTSD Index]). The convergent
      validity of the TSCYC and the Trauma Symptom Checklist for Children was weak,
      perhaps illustrating the lack of agreement often found between children and
      caregivers and illustrating the need for a multi-informant approach to screening
      and assessment of sexually abused children. The TSCYC seems to hold promise based
      on the emerging evidence for its convergent validity.

PMID- 19842318
TI  - Exploring the relations among the nature of the abuse, perceived parental
      support, and child's self-concept and trauma symptoms among sexually abused
      children.
AB  - This study examined two resiliency factors: self-concept and perceived parental
      support, in conjunction with abuse factors that impact psychological functioning.
      Data were collected on 61 sexually abused children prior to treatment. Findings
      indicate that a child's self-concept was associated with all the trauma symptoms
      except sexual concerns and did account for a significant amount of variance in
      relation to trauma symptomatology. Parental support was only associated with the
      Dissociation and was not found to account for variance in relation to trauma
      symptoms. Factors specific to the sexual abuse found that when a child endured a
      lengthy abuse period, their self-concept was more negative.

PMID- 19842319
TI  - Three types of memory for childhood sexual abuse: relationships to
      characteristics of abuse and psychological symptoms.
AB  - ABSTRACT. Data from a clinical sample (N = 88) reporting childhood sexual abuse
      was compared by types of memory, abuse characteristics, and psychological
      symptoms. Three types of memory were identified from a questionnaire ("Always" n
      = 27 [31%], "Recovered" n = 41 [46%], and "Both" n = 20 [23%]). When compared
      with narrative reports from a subset (n = 30) of the sample, the lines between
      "Always," "Recovered," and "Both" types of memory were ambiguous. Consistency
      across reports, however, was 83%. Memories classified as either "Recovered" or
      "Both" were associated with earlier age-at-onset and more severe psychological
      symptoms compared to those who "Always" remembered CSA. No significant
      differences were found between the "Both" and "Recovered" groups.

PMID- 19842320
TI  - Assessing posttraumatic stress disorder using the trauma symptom checklist for
      young children.
AB  - This pilot study assessed the performance of the Trauma Symptom Checklist for
      Young Children (TSCYC) in correctly classifying the presence or absence of PTSD,
      as determined by the Diagnostic Interview for children and Adolescents-Parent
      (DICA-P). Participants included 34 children, ages 4 to 12, referred for
      outpatient treatment. The 11 PTSD-positive participants scored significantly
      higher than the 23 PTSD-negative participants on scales assessing intrusive
      symptoms, arousal symptoms, and total posttraumatic stress (PTS). A model
      including the PTS-Intrusion, PTS-Avoidance, and PTS-Arousal scales, and the
      sexual concerns, dissociation, and anger/aggression scales correctly classified
      100% of the PTSD-negative and 72.7% of the PTSD-positive participants. These
      findings suggest that the TSCYC may be used as an economical and time-efficient
      screening device for PTSD.

PMID- 19842321
TI  - Remote sensing of particulate pollution from space: have we reached the promised
      land?
AB  - The Critical Review of Hoff and Christopher, along with the discussants, provides
      an important perspective on the interface between satellite measurement science
      and air quality observations. A top-down picture of the usefulness of satellite
      observations in terms of air quality regulatory and technical support
      requirements can be summarized. The air quality requirements are (1)
      determination of compliance with the ambient air quality standards, (2) inference
      of human and ecosystem exposure, (3) identification of intra- and
      intercontinental events relevant to EE, (4) establishment of trends in ambient
      concentrations relevant to accountability, (5) regulatory and forecast model
      applications, and (6) extension of fundamental knowledge relevant to air quality.
      Each of these topics is important to air quality management, and each has
      detailed technical issues associated with spatial and temporal resolution,
      accuracy, and precision, etc. In any case, one can summarize the broad
      capabilities of measurement systems to address these requirements as listed in
      Table 1. From this rather superficial summary table, investigators should be
      encouraged to forward increased interaction between the various measurement
      communities and to facilitate the utility of a comprehensive portfolio of
      measurements and adjunct analyses for improved air quality applications. The
      Critical Review has done much to educate air quality scientists on the
      possibilities for using satellite remote sensing for various purposes. However,
      space scientists also need a better education on air quality science. Recently
      published reviews on PM air quality measurements are available that complement
      the Hoff-Christopher paper on this topic. The need for greater collaboration of
      air quality and space scientists is evident in an article published in the July
      issue of the journal. Al-Hamdan et al. provide an interesting and useful analysis
      of relationships between surface air quality and space-based satellite AOD to
      estimate human exposure. They obtain mostly urban PM data from EPA's Air Quality
      System (AQS), but they neglect the potentially more useful PM2.5 and chemical
      speciation data from the nonurban Interagency Monitoring of Protected Visual
      Environments (IMPROVE) and the Southeastern Aerosol Research and Characterization
      (SEARCH) networks. They correlate PM2.5 mass with optical depth, although
      visibility assessments show that light extinction is better represented by a
      weighted sum of PM2.5 sulfate, nitrate, organic carbon, elemental carbon, and
      soil dust. Their comparison of hourly measurements with filter measurements does
      not specify the source of the hourly values as TEOM or BAM. Spatial outliers for
      ground-level measurements are removed to improve the correlation of PM2.5 with
      AOD, although these "outliers" are probably real values that relate to human
      exposure or a nearby source effect. The point here is not to overly criticize a
      good publication that will be highly cited. The intent is to demonstrate the
      value of air quality and space scientists working together more closely on this
      topic. This is something the review authors alluded to in their review, but if,
      as they concluded, the "promised land" has not been reached, then perhaps it is
      an appropriate time for the atmospheric community to ask, "Can near-term
      satellite observations play a role in characterizing broad-based (outdoor)
      exposure to pollutants and consequently influence public health improvement?"
      and, if so, then, "What comprehensive, integrated system is needed if satellite
      observations are to be used together with ground-based observations and modeling
      to continue improving air quality management options?"

PMID- 19842323
TI  - Effect of open channel filter on particle emissions of modern diesel engine.
AB  - Particle emissions of modern diesel engines are of a particular interest because
      of their negative health effects. The special interest is in nanosized solid
      particles. The effect of an open channel filter on particle emissions of a modern
      heavy-duty diesel engine (MAN D2066 LF31, model year 2006) was studied. Here, the
      authors show that the open channel filter made from metal screen efficiently
      reduced the number of the smallest particles and, notably, the number and mass
      concentration of soot particles. The filter used in this study reached 78%
      particle mass reduction over the European Steady Cycle. Considering the size
      segregated number concentration reduction, the collection efficiency was over 95%
      for particles smaller than 10 nm. The diffusion is the dominant collection
      mechanism in small particle sizes, thus the collection efficiency decreased as
      particle size increased, attaining 50% at 100 nm. The overall particle number
      reduction was 66-99%, and for accumulation-mode particles the number
      concentration reduction was 62-69%, both depending on the engine load.

PMID- 19842322
TI  - Zeolite formation from coal fly ash and its adsorption potential.
AB  - The possibility in converting coal fly ash (CFA) to zeolite was evaluated. CFA
      samples from the local power plant in Prachinburi province, Thailand, were
      collected during a 3-month time span to account for the inconsistency of the CFA
      quality, and it was evident that the deviation of the quality of the raw material
      did not have significant effects on the synthesis. The zeolite product was found
      to be type X. The most suitable weight ratio of sodium hydroxide (NaOH) to CFA
      was approximately 2.25, because this gave reasonably high zeolite yield with good
      cation exchange capacity (CEC). The silica (Si)-to-aluminum (Al) molar ratio of
      4.06 yielded the highest crystallinity level for zeolite X at 79% with a CEC of
      240 meq/100 g and a surface area of 325 m2/g. Optimal crystallization temperature
      and time were 90 degrees C and 4 hr, respectively, which gave the highest CEC of
      approximately 305 meq/100 g. Yields obtained from all experiments were in the
      range of 50-72%.

PMID- 19842324
TI  - Assessment of the ozone-nitrogen oxide-volatile organic compound sensitivity of
      Mexico City through an indicator-based approach: measurements and numerical
      simulations comparison.
AB  - The ozone (O3) sensitivity to nitrogen oxides (NOx, or nitric oxide [NO] +
      nitrogen dioxide [NO2]) versus volatile organic compounds (VOCs) in the Mexico
      City metropolitan area (MCMA) is a current issue of scientific controversy. To
      shed light on this issue, we compared measurements of the indicator species
      O3/NOy (where NOy represents the sum of NO + NO2 + nitric acid [HNO3] +
      peroxyacetyl nitrate [PAN] + others), NOy, and the semiempirically derived
      O3/NOz(surrogate) (where NOz(surrogate) is the derived surrogate NOz, and NOz
      represents NOx reaction products, or NOy - NOx) with results of numerical
      predictions reproducing the transition regimes between NOx and VOC sensitivities.
      Ambient air concentrations of O3, NOx, and NOy were measured from April 14 to 25,
      2004 in one downwind receptor site of photochemically aged air masses within
      Mexico City. MCMA-derived transition values for an episode day occurring during
      the same monitoring period were obtained through a series of photochemical
      simulations using the Multiscale Climate and Chemistry Model (MCCM). The
      comparison between the measured indicator species and the simulated spatial
      distribution of the indicators O3/ NOy, O3/NOz(surrogate), and NOy in MCMA
      suggest that O3 in this megacity is likely VOC-sensitive. This is in opposition
      to past studies that, on the basis of the observed morning VOC/NOx ratios, have
      concluded that O3 in Mexico City is NOx-sensitive. Simulated MCMA-derived
      sensitive transition values for O3/NOy, hydrogen peroxide (H2O2)/HNO3, and NOy
      were found to be in agreement with threshold criteria proposed for other regions
      in North America and Europe, although the transition crossover for O3/NOz and
      O3/HNO3 was not consistent with values reported elsewhere. An additional
      empirical evaluation of weekend/weekday differences in average maximum O3
      concentrations and 6:00- to 9:00-a.m. NOx and NO levels registered at the same
      site in April 2004 indirectly confirmed the above results. A preliminary
      conclusion is that additional reductions in NOx emissions in MCMA might cause an
      increase in presently high O3 levels.

PMID- 19842326
TI  - Titanium dioxide/zeolite catalytic adsorbent for the removal of NO and acetone
      vapors.
AB  - This study delineates a simple and versatile approach for the removal of nitrogen
      monoxide (NO) and volatile organic vapors over composites of titanium dioxide
      (TiO2) catalyst/zeolite adsorbent under ultraviolet (UV) irradiation at ambient
      temperature. The catalytic adsorbents with different TiO2/H-ZSM-5 zeolite ratios
      were prepared by a simple insipient wetness impregnation method. It was found
      that a 60%/40% weight ratio of TiO2/H-ZSM-5 composite is most effective and can
      achieve over 90% efficiency for the removal of NO and acetone vapors. This
      composite also showed a better long-term activity than that of bulk TiO2
      photocatalyst or zeolite adsorbent. The experimental results revealed that
      photocatalytic decomposition of NO was dramatically enhanced in the presence of
      acetone. NO also promoted the acetone oxidation under humid conditions.
      Furthermore, the co-existence of acetone and NO in the gaseous stream could
      reduce acid accumulation on the surface of the catalyst as confirmed by Fourier
      transform infrared spectroscopy. Thus, the TiO2/zeolite catalytic adsorbent could
      have a high potential for the removal of multiple air pollutants in the indoor
      air environment.

PMID- 19842325
TI  - Using a continuous time lag to determine the associations between ambient PM2.5
      hourly levels and daily mortality.
AB  - The authors are interested in understanding the possible association between
      exposure to short-term fine particulate matter (PM2.5) peaks that have changing
      physical characteristics throughout the day and observable health outcomes (daily
      mortality). To this end, modern statistical methods are used here that allow for
      a continuous time lag between hourly PM2.5 mass concentration and daily
      mortality. The functional linear regression model was used to study how hourly
      PM2.5 mass of past days continuously influences the daily mortality count of the
      current day. Using a Poisson likelihood with the canonical link, the authors
      found that a 10-microg/m3 increase in the hourly PM2.5 above the hourly average
      is associated with 1.7% (0.1, 3.4), 2.4% (1.2, 3.7), 1.6% (0.6, 2.7), and 0.8% (
      0.2, 1.8) higher risk of mortality on the same day, next day, 2 days, and 3 days
      later, respectively. The increase in relative risk is statistically significant
      for lags of 0-2 days, but not at lag 3. The highest association between PM2.5
      mass concentration and daily mortality was found to occur in the morning when
      both mass and PM number concentrations peak at approximately 8:00 a.m. (lag of
      15, 39, and 63 hr). This morning time interval corresponds to automobile traffic
      rush hour that coincides with a morning atmospheric inversion that traps high
      concentrations of nanoparticles.

PMID- 19842327
TI  - Global climate change and the mitigation challenge.
AB  - Anthropogenic emissions of greenhouse gases, especially carbon dioxide (CO2),
      have led to increasing atmospheric concentrations, very likely the primary cause
      of the 0.8 degrees C warming the Earth has experienced since the Industrial
      Revolution. With industrial activity and population expected to increase for the
      rest of the century, large increases in greenhouse gas emissions are projected,
      with substantial global additional warming predicted. This paper examines forces
      driving CO2 emissions, a concise sector-by-sector summary of mitigation options,
      and research and development (R&D) priorities. To constrain warming to below
      approximately 2.5 degrees C in 2100, the recent annual 3% CO2 emission growth
      rate needs to transform rapidly to an annual decrease rate of from 1 to 3% for
      decades. Furthermore, the current generation of energy generation and end-use
      technologies are capable of achieving less than half of the emission reduction
      needed for such a major mitigation program. New technologies will have to be
      developed and deployed at a rapid rate, especially for the key power generation
      and transportation sectors. Current energy technology research, development,
      demonstration, and deployment (RDD&D) programs fall far short of what is
      required.

PMID- 19842328
TI  - Estimating mortality effects of fine particulate matter in Japan: a comparison of
      time-series and case-crossover analyses.
AB  - Small particles can reach alveoli without being trapped in the upper respiratory
      tract and may have a greater impact on health than larger particles. Given the
      limited knowledge on health effects of fine particulate matter (PM2.5) in Japan,
      the short-term effects of PM2.5 on daily mortality using the generalized additive
      model (GAM), generalized linear model (GLIM), and time-stratified case-crossover
      analysis were estimated. Daily mortality data were obtained from the Ministry of
      Health, Labor, and Welfare. Air pollution and meteorological data in 20 areas
      were obtained from the National Institute for Environmental Studies and the Japan
      Meteorological Agency, respectively. The three methods were compared, adjusting
      for meteorological variables and co-pollutants, for area-specific analyses and
      combined area-specific results using meta-analysis with a random-effects model.
      Daily mortality for elderly aged 65 and over varied from 0.5 to 127.3 by area.
      The 24-hr mean concentration of PM2.5 ranged from 11.8 to 22.8 microg/m3. Area
      specific analyses revealed regional heterogeneity. Furthermore, combined results
      showed that a 10-microg/m3 increase in PM2.5 for the single-pollutant model at
      lag1 was associated with a 0.53, 0.77, and 0.88% increase in all-cause mortality
      for the GAM, GLIM, and case-crossover analysis, respectively. These findings
      provide robust evidence for the short-term effects of air pollutants on daily
      mortality in Japan and suggest that differences in estimates obtained from
      different statistical models should be considered when multipollutant models are
      used.

PMID- 19842329
TI  - Fugitive dust emissions from paved road travel in the Lake Tahoe basin.
AB  - The clarity of water in Lake Tahoe has declined substantially over the past 40
      yr. Causes of the degradation include nitrogen and phosphorous fertilization of
      the lake waters and increasing amounts of inorganic fine sediment that can
      scatter light. Atmospheric deposition is a major source of fine sediment. A year
      round monitoring study of road dust emissions around the lake was completed in
      2007 using the Testing Re-entrained Aerosol Kinetic Emissions from Roads (TRAKER)
      system developed at the Desert Research Institute (DRI). Results of this study
      found that, compared with the summer season, road dust emissions increased by a
      factor of 5 in winter, on average, and about a factor of 10 when traction control
      material was applied to the roads after snow events. For winter and summer, road
      dust emission factors (grams coarse particulate matter [PM10] per vehicle
      kilometer traveled [g/vkt]) showed a decreasing trend with the travel speed of
      the road. The highest emission factors were observed on very low traffic volume
      roads on the west side of the lake. These roads were composed of either a 3/8-in.
      gravel material or had degraded asphalt. The principle factors influencing road
      dust emissions in the basin are season, vehicle speed (or road type), road
      condition, road grade, and proximity to other high-emitting roads. Combined with
      a traffic volume model, an analysis of the total emissions from the road sections
      surveyed indicated that urban areas (in particular South Lake Tahoe) had the
      highest emitting roads in the basin.

PMID- 19842330
TI  - Treatment of acetone waste gases using slurry-phase airlift embedded with
      polyacrylamide-entrapped cell beads.
AB  - Acetone is the most common chemical used in the Hsin-chu Science Park in Taiwan.
      The three-phase airlift bioreactor was designed to absorb acetone into the 39 L
      of medium solution and then degraded by 2-L polyacrylamide (PAA)-entrapped
      Thiosphaera pantotropha cell beads. The airlift medium was successfully
      regenerated and circulated for more than 5 months. The elimination capacity of
      350-part per million (ppm) acetone at 10 L x min(-1) was 258.4 g x m(-3) hr(-1)
      (160.4 g-C x m(-3) hr(-1)) with 100% removal efficiency in Stage II, higher than
      previously reported biofiltration results. The maximum chemical oxygen
      demand:nitrogen ratio of 100:2.9 is achieved, and a balanced nutrient state was
      indicated by the change in redox potential. The pH of the system was maintained
      at neutral because of the strong buffer agent added to the medium (final buffer
      intensity, beta = 1.18 x 10(-2) M). The PAA-entrapped cell beads could also
      provide a good barrier for high salinity gradient environment and the inoculum
      source to maintain steady operation of the system.

PMID- 19842331
TI  - Could ozonation technology really work for mitigating air emissions from animal
      feeding operations?
AB  - Among various mitigation technologies for ammonia (NH3) emission control at
      animal feeding operations (AFOs), room ozonation technology is the most
      controversial. This paper aims to present full perspectives of ozonation
      techniques through a literature review and a series of laboratory experiments. In
      the literature review, ozone chemistry was summarized to address (1) ozone and
      NH3 reactions, (2) ozone and odor reactions, (3) ozone and particulate matter
      reactions, and (4) ozone and microorganism reactions. A series of laboratory
      experiments were conducted in a dual large outdoor aerosol smog chamber (270 m3).
      NH3 and fine particle number concentrations from ozone-treated and control
      experiments were compared. The experimental results indicated that (1) ozone has
      no significant effect on NH3 emissions/concentrations or NH3 decay of an outdoor
      chamber; and (2) with ozone treatment, high concentration of particles in the
      "high-risk" respiratory fraction (in submicron range) are generated.

PMID- 19842332
TI  - Hospital and asylum visiting in historical perspective: themes and issues.
AB  - Compared to doctors, patients and institutions, visitors are an understudied
      constituency in medical history. The collection of essays in this book situates
      the historical practice of hospital and asylum visiting in broad social, cultural
      and geographical perspectives. This introduction loosely categorises visitors
      into four groups: patient visitors, including family and friends; public
      visitors, such as entertainers, tourists and the clergy, who have no direct
      formal ties with the institution or the patients; house visitors involved with
      the management and government of the hospital; and official visitors, who have
      inspectorial responsibilities. Discussion of the wider historical significance of
      visiting draws attention to issues such as urban governance, philanthropy, the
      public sphere, civil society and citizenship.

PMID- 19842333
TI  - Receiving the rich, rejecting the poor: towards a history of hospital visiting in
      nineteenth-century provincial England.
AB  - The changing perceptions of visitors to hospitals in provincial England during
      the long nineteenth century are examined in this chapter. In particular, it
      discusses the experience of visitors to hospitals in nine general and specialist
      hospitals in Birmingham, England's 'second city'. Though the history of visitors
      in this provincial setting supports the general assumption that hospital
      governors received the rich and rejected the poor, this chapter demonstrates that
      attitudes to visitors were not always straightforward. Views of hospital
      governors and medical staff varied with medical specialism, hospital finances,
      and a host of other factors.

PMID- 19842334
TI  - 'Family-centred care' in American hospitals in late-Qing China.
AB  - Today, patients' families in the West are regaining the access to hospitals that
      they lost when hospitals emerged as the primary site for medical treatment,
      research and training at the beginning of the twentieth century. In China,
      however, families were never excluded from American mission-run hospitals, in
      fact, they were indispensable. Families were in the waiting rooms, consulting
      rooms,wards and operating theatres. They provided more than reassurance and
      comfort: they fed and nursed their sick relatives, acted as advocates and
      middlemen and may even have lowered the incidence of cross-infection, the scourge
      of the contemporary hospital in the West.

PMID- 19842335
TI  - Care, nurturance and morality: the role of visitors and the Victorian London
      children's hospital.
AB  - Visitors at the Hospital for Sick Children, Great Ormond Street, fulfilled an
      economic, social and marketing role at an institution which, in its earliest
      years, struggled against significant opposition from medical and charitable
      critics. Men and women from the respectable classes found a function that
      reflected well their philanthropic credentials, and that also opened up social
      and professional opportunities. The parents and families of the patients,
      however, found themselves marginalised by the hospital, and granted little scope
      to influence the hospital experience of their children or to interact with the
      supporters of the institution.

PMID- 19842336
TI  - Pariahs or partners? Welcome and unwelcome visitors in the Jenny Lind Hospital
      for Sick Children, Norwich, 1900-50.
AB  - The idea of 'visitors' when applied to hospitals may appear simple and
      uncontroversial: relatives or friends keeping the sick person company, lifting
      the spirits and offering support. The reality was more complex and challenging,
      particularly in the care of child patients. The Jenny Lind Hospital for Sick
      Children constantly evolved its relationship with visitors in the first half of
      the twentieth century. Two major variables are discussed in this chapter: the
      changing importance of the visitors themselves and the way in which the Jenny
      Lind defined and adapted its perspective on visitors and the nature of visiting.

PMID- 19842337
TI  - Visiting children with cancer: the parental experience of the Children's Hospital
      of Pittsburgh, 1995-2005.
AB  - This chapter examines the unique role of parental visitors of children with
      cancer at the Children's Hospital of Pittsburgh, 1995 to 2005. Using oral
      interviews with parents, medical and psychosocial staff, the study explores the
      experiences of parents while in hospital with their children and the social,
      emotional, financial and family issues they confronted during these admissions.
      Parents in their stories identified the various roles they assumed as their
      children experienced illness, treatment, side effects and psychosocial issues.
      The study also questions the relative importance of family dynamics, race, and
      socio-economic status as these related to parents' roles and perceptions.

PMID- 19842338
TI  - Infection and citizenship: (not) visiting isolation hospitals in mid-Victorian
      Britain.
AB  - Local authority provision for the sequestration of infectious people mushroomed
      in Great Britain from the mid-1860s. By the First World War, more than 750
      isolation hospitals contained almost 32,000 beds for infectious patients, most of
      whom were children. Trips to an isolation hospital were problematic because
      visitors might contract infection there and spread it to the wider community.
      Various strategies sought to minimise this risk or eliminate it altogether. This
      chapter argues that the management of isolation hospital visitors was typical of
      Victorian public health's tendency to regulate people's behaviour. By granting
      rights to, and conferring responsibilities on, the relatives of patients,
      visiting practices enshrined notions of citizenship that sought to govern
      'through' the family.

PMID- 19842339
TI  - Stage-managing a hospital in the eighteenth century: visitation at the London
      Lock Hospital.
AB  - London's Lock Hospital, established in 1747 to treat venereal diseases, depended
      heavily on charity. Its administrators tried valiantly to project a positive
      image of the hospital in spite of the pervading moral assumptions about its
      patients and doubts about whether they deserved charity. Policies governing
      visitation were bound up in the hospital's attempts to police itself and promote
      its cause to benefactors. Visitation policies served numerous ends, including
      policing patients, introducing moral reform, monitoring the staff, and obscuring
      the reality of the wards from public view, ensuring that prospective donors only
      saw what administrators wanted them to see.

PMID- 19842340
TI  - 'The keeper must himself be kept': visitation and the lunatic asylum in England,
      1750-1850.
AB  - There was a growing disquiet in eighteenth-century England about the activities
      of private madhouses. Early legislation, in 1774, gave limited powers of
      registration and inspection to local magistrates.The exposure of flagrant abuses
      in both private and public institutions by a parliamentary select committee, in
      1815, brought the question of visitation to the centre of the lunacy reform
      agenda. Subsequent legislation extended the responsibilities of magistrates and
      also established the principal of centralised oversight. An effective national
      system of regulation was finally created in 1845, with Commissioners in Lunacy
      required to provide formal visitation to all public and private asylums.

PMID- 19842341
TI  - 'A disgrace to a civilised community': colonial psychiatry and the visit of
      Edward Mapother to South Asia, 1937-8.
AB  - In 1937, Edward Mapother, Medical Superintendent of the Maudsley Hospital in
      London, took a trip around the mental hospitals of Britain's dominions in South
      Asia. The result was a series of documents that provide a snapshot of psychiatry
      in India and Ceylon in the twilight years of the British Empire. This chapter
      will consider Mapother's reports from a number of perspectives in order to assess
      the politics and the impact of an expert 'visitor' to a colonial medical system.

PMID- 19842342
TI  - 'In view of the knowledge to be acquired': public visits to New York's asylums in
      the nineteenth century.
AB  - This chapter examines asylum tourism in nineteenth-century New York. It argues
      that the popularity of visits by the public undermines the notion that asylums
      were segregated from greater society, and instead, suggests that these
      institutions were deeply embedded within the social and cultural landscape of the
      time. While challenging many of our assumptions regarding the relationship of
      asylums with their greater communities, the phenomenon of visiting enhances our
      understanding of both popular attitudes towards the mentally ill and the
      experiences of patients themselves. As people believed asylums represented
      something remarkable in society, visiting provides new perspectives on the social
      role of these institutions and nineteenth-century cultural practices more
      generally.

PMID- 19842343
TI  - 'Amusements are provided': asylum entertainment and recreation in Australia and
      New Zealand c.1860-c.1945.
AB  - This chapter examines the official 'entertainment', in all its forms, provided to
      inmates in Australian and New Zealand asylums--later mental hospitals--between
      c.1860 and c.1945. Visitors came into asylum grounds and patients were permitted
      periods of leave, all for the purposes of entertainment and recreation. Surviving
      recreation buildings, their grounds and institutional archives, bear silent
      witness to the noisy and lively recreational activities of past patients, staff
      and visitors. This chapter reconstructs these practices in twenty public and
      three private asylums from this period by examining a diverse range of sources,
      including archives, histories of asylums and newspaper articles.

PMID- 19842344
TI  - Challenging institutional hegemony: family visitors to hospitals for the insane
      in Australia and New Zealand, 1880s-1910s.
AB  - Historians have increasingly come to identify that there was considerable traffic
      between nineteenth-century psychiatric institutions and the world beyond, with
      official visitors recording details of their regular forays inside asylum walls,
      and sometimes family members visiting the institution to check on treatments,
      patients' progress and welfare. This chapter explores the broad array of
      experiences of asylum visitors in colonial Australia and New Zealand, focusing on
      families and their responses to the institution. It draws upon a range of
      materials to show that visitors found their way inside the hospital for the
      insane, both in their letters and through their actual physical presence. Through
      these glimpses, it suggests that the asylum itself should be unsettled as the
      focus of all the meanings of insanity and its cure.

PMID- 19842345
TI  - The Twenty-Sixth Annual Meeting of the International Tinnitus Forum, September
      20, 2008, Chicago, IL.

PMID- 19842346
TI  - Final common pathway for tinnitus: theoretical and clinical implications of
      neuroanatomical substrates.
AB  - A final common pathway (FCP) for tinnitus has been hypothesized since 1989 for
      all clinical types of tinnitus, particularly subjective idiopathic tinnitus (SIT)
      of the severe disabling type. This was intended to explain the transformation
      transition of the sensation of an aberrant auditory sensation-tinnitus (i.e., the
      sensory component)-to one of affect (i.e., the emotional-behavioral component)
      or, conversely, that an emotional-behavioral stimulus (affect) can result in the
      clinical manifestation of a sensation (a sensory stimulus). Understanding the
      pathophysiology of this transformation is fundamental for the diagnosis of
      tinnitus and the treatment of the patient, and it presents a dilemma to basic
      science, neuroscience, and clinical medicine. Clinically, tinnitus is not a
      unitary symptom; it constitutes many clinical types; can have its origin in the
      auditory or nonauditory systems and in the peripheral or central nervous system;
      and may be clinically manifest or subclinical. Accumulating evidence is presented
      to support the original hypothesis of an FCP. The resolution of this dilemma
      involves sensory processing (i.e., the integration, identification, and
      understanding of the ongoing, underlying, simultaneous, multiple associated brain
      function processes not only from one sensory modality but from multiple sensory
      modalities accompanying and associated with an FCP). In the FCP, the predominant
      brain function process is that of the sensory-affect transformation of a
      sensation and its conscious awareness by the affected patient. The
      neuroanatomical substrates identified in 1989 in tinnitus patients (reported
      originally in 1991 and published in 1995) are presented as a common framework for
      the hypothesis of an FCP. They further the understanding of the clinical
      heterogeneity of the tinnitus symptom, clinically manifest as multiple brain
      functions associated with the clinical course of tinnitus patients, particularly
      those with SIT. The FCP provides a model for tinnitus theory, diagnosis, and
      treatment. The FCP is not a tinnitus theory. Specifically, it is a hypothesis
      that attempts to explain how an aberrant auditory sensory stimulus becomes
      transformed into one of affect and somatomotor response. The neuroanatomical
      substrates of the FCP provide a basis for the identification of the involved
      neurocircuitries and neurochemistries. The physiology and biochemistry underlying
      the neuroanatomical substrates of the FCP provide a basis for translation for
      tinnitus diagnosis and treatment. The neuroanatomical substrates of the FCP are
      presented as algorithms of (1) components of a sensation (i.e., sensory, affect,
      and psychomotor), a translation from basic sensory physiology for tinnitus; (2)
      clinically manifest biophysiological brain functions and underlying processes
      associated with the tinnitus; (3) a model for investigation of metabolic
      electrophysiological correlates for tinnitus; (4) the basis for an integrated
      theory of tinnitus and brain function (i.e., tinnitus dyssynchrony-synchrony
      theory; (5) a model for the identification of underlying neurocircuitries and
      neurochemistries involved in brain for the sensory-affect transformation of an
      aberrant auditory stimulus (tinnitus); (6) a model for the selection-introduction
      of innovative therapies attempting tinnitus relief; and (7) its clinical
      translation for objective monitoring systems for the determination of the
      efficacy of modalities of therapy attempting tinnitus relief. The hypothesis of
      the FCP for tinnitus and the identified neuroanatomical substrates, when viewed
      in terms of the physiology of sensory processing, is considered to be expanded
      and broader in its application for all sensations, normal or aberrant.

PMID- 19842347
TI  - The windowed sound therapy: a new empirical approach for an effectiv personalized
      treatment of tinnitus.
AB  - We auditorily stimulated patients affected by subjective tinnitus with broadband
      noise containing a notch around their tinnitus frequency. We assessed the long
      term effects on tinnitus perception in patients listening to notched noise
      stimuli (referred to as windowed sound therapy [WST]) by measuring the variation
      of subjects' tinnitus loudness over a period of 2-12 months. We tested the
      effectiveness of WST using non-notched broadband noise and noise of water as
      control sound therapies. We found a significant long-term reduction of tinnitus
      loudness in subjects treated with notched noise but not in those treated with
      control stimulations. These results point to the importance of the personalized
      sound treatment of tinnitus sufferers for the development of an effective
      tinnitus sound therapy.

PMID- 19842348
TI  - Transcranial magnetic stimulation: summary of the proceedings of the Twenty-Sixth
      Annual Meeting of the International Tinnitus Forum.

PMID- 19842349
TI  - Investigation of auditory brainstem function in elderly diabetic patients with
      presbycusis.
AB  - We performed brainstem auditory evoked potential (BAEP) examinations in 100
      patients older than 60 years and having type I diabetes mellitus and presbycusis.
      The aim of our investigation was to compare the BAEP results of this group with
      those of healthy controls with presbycusis and to look for possible correlations
      between alteration of the auditory brainstem function and the aging of elderly
      diabetic patients. Absolute and interpeak latencies of all waves were prolonged
      significantly in the study group of diabetic patients. The amplitudes of all
      waves I through V were diminished in the study group as compared to those in the
      control group, with statistical significance present for all waves. Analysis of
      the latencies (waves I, II, I, and V), interpeak latencies (I-V), and amplitudes
      (I, II, III, and V) of BAEP revealed a significant difference between those of
      diabetics and those of healthy elderly controls with presbycusis. These data
      support a hypothesis that there is a brainstem neuropathy in diabetes mellitus
      that can be assessed with auditory brainstem response testing even in the group
      of elderly patients with sensorineural hearing loss.

PMID- 19842350
TI  - Disequilibrium and its management in elderly patients.
AB  - Dizziness, a frequent occurrence in the elderly, carries substantial health and
      quality-of-life consequences for patients. Disequilibrium of the elderly refers
      to dizziness or ataxia (or both) without apparent localizing signs and is
      typically attributed to the aging process.In many cases, disequilibrium is
      multifactorial and worsened or triggered by multiple medications and
      iatrogenicity. This review provides an update of the literature concerning
      elderly multifactorial imbalance and discusses factors that may trigger falls.
      The author reviewed the underlying pathophysiology of disequilibrium along with
      an assessment of how current evaluation methods and exercise protocols are used
      to help prevent falls in the elderly. Patients must be stimulated to perform
      customized physical exercises under safe conditions, considering their general
      state of health. The objectives of current programs are to encourage patients to
      develop an efficient personalized strategy of equilibrium and to increase their
      level of physical activity, autonomy, and safety to reduce the potential for
      falls.

PMID- 19842351
TI  - Inner-ear function test in cases of posterior canal-type benign paroxysmal
      positional vertigo.
AB  - Otolaryngologists typically perform diagnoses and offer medical treatment for
      vestibular dysfunction. This vestibular dysfunction manifests as benign
      paroxysmal positional vertigo (BPPV), Meniere's disease, vestibular neuronitis,
      and so on. The etiology of BPPV is still not clear, so in this article we discuss
      inner-ear function, etiology, and factors related to BPPV. We examined by pure
      tone audiometry and hot and cold caloric tests patients whom we identified as
      having diagnosed posterior canal-type BPPV. We observed canal paresis at a high
      rate on the affected side (p < .01). The term of recovery at the first treatment
      was longer in patients with canal paresis as compared to those without.
      Deterioration of hearing level was observed more frequently on the affected side
      (p < .01). The horizontal semicircular canal and cochlea are important potential
      sites of lesions affecting posterior canal-type BPPV, and the posterior circular
      canal and otolith are already considered to be sites of affecting lesions.

PMID- 19842352
TI  - The effect of a new treatment based on somatosensory stimulation in a group of
      patients with somatically related tinnitus.
AB  - The aim of this study was to evaluate the effect of a new treatment consisting of
      stretching, posture training, and auricular acupuncture immediately and at a 3
      month followup. This method has not been tested previously. From an original pool
      of 41 potential subjects, we recruited 24 (12 men, 12 women; ages 18-70 years)
      into this study and divided them from a waiting list into either a treatment
      group or a control group. We measured mobility of neck and posture; measured
      severity of tinnitus by the Klockhoff test and the visual analog scale (VAS); and
      measured grade of anxiety and depression with the Hospital Anxiety and Depression
      Scale. We also used the Mann-Whitney U-test to determine statistical
      significance. The statistical analysis demonstrated a significant decrease of
      tinnitus in the treatment group as compared with the control group, according to
      the VAS before and after treatment (p < .001) and at follow-up after 3 months (p
      < .01). We also observed a significant decrease of tinnitus according to the
      Klockhoff test before and after treatment (p < .001) and at follow-up after 3
      months (p < .01). Our study indicates that this method, based on somatosensory
      stimulation, may be a useful and alternative treatment of somatic tinnitus.

PMID- 19842353
TI  - Transtympanic electrical stimulation for immediate and long-term tinnitus
      suppression.
AB  - Tinnitus is a common symptom which often becomes disabling, affecting the
      emotional and psychosocial dimensions of life. There are many reports describing
      tinnitus suppression or attenuation through electrical stimulation of the ear,
      provided either by cochlear implants or by transtympanic stimulation. Our study
      project aims to assess the effects of electrical promontory stimulation (EPS) on
      persistent disabling tinnitus. We enrolled 11 patients affected by postlingual
      monoaural or binaural profound hearing loss and disabling tinnitus in the worse
      ear. EPS was performed with direct continuous positive current delivered by an
      active platinum-iridium needle electrode connected to a promontory stimulator
      device. The short-term effect on tinnitus was assessed during and immediately
      after the stimulation. Long-term effects were estimated after one month by
      comparing pre- and post-EPS Tinnitus Handicap Inventory (THI) scores. Immediately
      after EPS, five patients (45.4%) reported complete suppression and four (36.4%)
      reported attenuation of tinnitus. Two patients (18.2%) said it was unchanged.
      After one month, the THI score was reduced in five patients (45.4%) and remained
      unchanged in the other six patients (54.6%). The beneficial effects of EPS on
      tinnitus might be explained by interference with tinnitus generating circuits
      such as the dorsal cochlear nucleus and the inferior colliculus and by
      modification of cortical activity. EPS is to be considered a worthwhile attempt
      at tinnitus suppression, and could help select candidates for the positioning of
      an implantable electrical stimulator that might provide longer-term beneficial
      effect on tinnitus.

PMID- 19842354
TI  - Introduction: women, depression, and the struggle for control over the evaluation
      of self-worth.
AB  - The papers in this volume present both quantitative and qualitative studies on
      the various stages of women's experiences with depression including the
      antecedents of depression, dysfunctional reactions to depressive symptoms, and
      services and resources available in the community for depressed women. A
      recurrent theme in the findings of these studies is that depressed women tend to
      apply negative socially-derived and externally-imposed cognitive constructs or
      frames of reference by which they evaluate their self-worth. Having lost the
      social struggle over the control of these frames of reference, they become
      entrapped in cognitive constructs in which the self is seen as rejected,
      subordinate, and as a passive victim of hostile circumstances. The evidence
      suggests that psychological, social, and community interventions for depressed
      women need to encourage and empower them to own and control the processes of
      positive and constructive self-evaluation.

PMID- 19842355
TI  - Self-silencing, anger and depressive symptoms in women: implications for
      prevention and intervention.
AB  - The study investigated Jack's silencing the self theory by examining the links
      among severity of depressive symptoms, self-silencing, anger expression and anger
      suppression in women. The predictors of depressive symptoms were anger
      suppression and two facets of self-silencing as measured with Jack's Silencing
      the Self Scale (STSS): Externalized Self-Perception and Self-Silencing. Women in
      the high depression group scored higher than those in the low depression group in
      anger expression, anger suppression, and in all four facets of STSS: Externalized
      Self-Perception, Care as Self-Sacrifice, Self-Silencing, and Divided Self.
      Findings are discussed with implications for preventive and intervention
      strategies for depression in women.

PMID- 19842356
TI  - Motivational orientation, expectancies, and vulnerability for depression in
      women.
AB  - In this study, motivational components in the personal styles of sociotropy and
      autonomy were examined in a sample of 284 women. One hypothesis was that self
      validation needs would account for the vulnerability for depressive symptoms in
      these personal styles. A second hypothesis was that the association of these
      personal styles with depressive symptoms would be moderated by expectations and
      perceptions of how likely these validation needs would be met. As predicted, it
      was found that validation seeking mediated the association of sociotropy and
      autonomy with depressive symptoms in these women. Another finding was that
      expectancies moderated the effects of sociotropy and autonomy to predict
      depressive symptoms. Negative expectancies in women high on these personal styles
      together further increased the level of depressive symptoms. These findings are
      compatible with theories emphasizing the importance of situational factors in the
      onset and maintenance of depression in women.

PMID- 19842357
TI  - Exploring perceptions of alcohol use as self-medication for depression among
      women receiving community-based treatment for alcohol problems.
AB  - Although epidemiological literature reports a significant overlap between
      depression and alcoholism among women, the dynamics of this relationship requires
      further exploration. The present paper documents significant lifetime histories
      of depression among women in treatment for alcohol problems, and presents
      findings on these women's experiences of the relationship between depression and
      alcohol use problems. In this community-based treatment sample, 18 out of 18
      women participating in qualitative interviews reported histories of depression
      and almost 80% were currently using anti-depressant medication. The use of
      alcohol as an attempt to escape difficult emotions or alternatively to produce
      positive emotional experiences is discussed within the gendered context of the
      stories women tell about their depression and alcohol use.

PMID- 19842358
TI  - Depressive symptoms, gender, and sexual risk behavior among African-American
      adolescents: implications for prevention and intervention.
AB  - African-American youths are disproportionately affected by deleterious outcomes
      associated with risky sexual activity. Arguably, females are at greater risk for
      these adverse outcomes due to physiological and emotional risk factors, such as
      depression. The current study examines the relationship between depressive
      symptomology and sexual risk behavior within a sample of 1,970 inner-city,
      economically disadvantaged African-American adolescents in grades nine and
      eleven. The findings of this study support a relationship between sexual risk
      behavior and depressive symptomology for the sample, such that as depressive
      symptomology increases so does sexual risk behavior. Furthermore, an interaction
      for gender was found, with depressive symptomology being a stronger predictor of
      sexual risk behavior for African-American females as compared to African-American
      males. Implications of these findings for the design of prevention programs
      specifically tailored to African-American adolescent women are discussed.

PMID- 19842359
TI  - The needs of depressed women: perspectives of family physicians.
AB  - Twenty family physicians (11 female and 9 male) were interviewed about their
      experiences in treating depressed patients. Interview transcripts were analyzed
      thematically with respect to physicians' understanding of women's depression and
      their treatment strategies with depressed women. Stress arising in the social
      context of women's lives was perceived as a key precipitant of depression in
      women, with family-related, gender-specific and practical sources of stress as
      the main contributors. Physicians' treatment strategies had the aims of
      alleviating depressive symptoms and stress reduction. Implications of the
      findings for primary health care delivery and community-based interventions with
      depressed women are discussed.

PMID- 19842360
TI  - Community service providers' conceptualizations of the needs and services of
      depressed rural women.
AB  - Representatives from community and volunteer organizations (N = 37) in a rural
      region of Nova Scotia were interviewed on their views of the causes, prevention
      and treatment of depression in rural women. Utilizing a qualitative analysis,
      five themes were identified in their responses: the needs and stresses of women
      with depression; the problems of women in rural areas; obstacles and barriers to
      accessing services; the inadequacy of treatment services; and recommendations for
      improving prevention and treatment. The findings suggested that community service
      providers were consistent in their views of the needs and stresses of depressed
      women in rural areas and the kinds of services that would remedy them. Making
      community service providers aware of the consistencies in their views may promote
      more inter-agency cooperation and the development of community-centered
      approaches to the treatment of depression in rural women.

PMID- 19842361
TI  - The review of the changes of Britain's National Health Service for the impending
      change of the United States.

PMID- 19842362
TI  - A critique of the changes in Hawai'i's Medicaid system.

PMID- 19842363
TI  - Strategies to increase breast and cervical cancer screening among Hawaiian,
      Pacific Islander, and Filipina women in Hawai'i.
AB  - The Hawai'i Breast and Cervical Cancer Control Program (BCCCP) offers free
      mammograms and Pap smears to women who are uninsured or underinsured through a
      statewide provider network. Native Hawaiians, Pacific Islanders and Filipinas are
      priority populations for this program, and BCCCP providers are required through
      contract with the Hawai'i Department of Health to utilize half of their allotted
      mammograms and Pap smears for eligible women from these groups. To identify
      strategies for increasing use by these groups of mammographyand Pap smear
      screening services through BCCCP, we held focus groups with women who could
      potentially use BCCCP services, and we conducted key informant interviews with 9
      of Hawai'i's 11 BCCCP providers and 9 non-BCCCP outreach workers serving these
      populations. Findings led to recommendations for promoting awareness of BCCCP and
      enhancing outreach to Native Hawaiian, Pacific Islander and Filipina communities
      in Hawai'i.

PMID- 19842364
TI  - Language preference and development of dementia among bilingual individuals.
AB  - In bilingual individuals, regression to a primary language may be associated with
      development of cognitive impairment and increased risk for development of
      dementia. This report describes two bilingual patients who presented with early
      symptoms of dementia after regression to their primary language. The results of
      this study may help clinicians identify aging bilingual patients who are
      beginning to develop cognitive impairment or dementia and suggest that further
      studies on the long term cognitive effects of bilingualism and interactions with
      the aging process are indicated.

PMID- 19842365
TI  - Risk of parasitic worm infection from eating raw fish in Hawai'i: a physician's
      survey.
AB  - Public health concerns have been raised over the risk of parasitic helminth
      (roundworm, tapeworm and fluke) infections from eating raw fish, an increasing US
      consumer trend. Hawai'i consumers eat seafood at nearly 3 times the US national
      average rate, with a long tradition and high level of raw fish consumption. The
      local fish species commonly eaten raw in Hawai'i include tuna (bigeye, yellowfin,
      albacore and skipjack), marlin (blue and striped) and deepwater snappers (long
      tailedred, pink and blue green). Forty-eight Hawai'i-based physicians
      (gastroenterologists, internists, general and family practitioners) were surveyed
      to count known cases of parasitic worm infection linked to raw fish consumption
      and to explore physicians' perceptions of risk associated with the consumption of
      fresh, never frozen local fish with an emphasis on raw tuna and skipjack. No
      single known case of helminth infection due to consumption of raw tuna or
      skipjack, or other local fish species caught in Hawai'i was reported. The
      majority of the physicians surveyed reported that they eat raw yellowfin and
      bigeye tuna, also eat raw skipjack and do not think that these fish present a
      significant health risk of helminthic parasites. The survey results support the
      conclusion that the risk of parasitic helminth infection from the consumption of
      Hawai'i-caught tuna, skipjack, marlin and deepwater snappers is negligible.

PMID- 19842366
TI  - The role of global health in medical education at JABSOM.

PMID- 19842367
TI  - Partial purification and characterization of Trichomonas vaginalis DNA
      topoisomerase II.
AB  - DNA topoisomerases regulate conformational changes in DNA topology by catalyzing
      the breakage and rejoining of DNA strands during the cell cycle. These processes
      are essential for the multiplication of cells, and inhibition of these reactions
      stops cell division and cell growth. Drug resistance to Trichomonas vaginalis, a
      common sexually transmitted protozoan parasite, is increasing worldwide, and DNA
      topoisomerase II may provide a new target for anti-trichomonal drug development.
      In this study, T. vaginalis DNA topoisomerase II was partially purified from a
      large scale axenic culture using fast protein liquid chromatography with a yield
      of 0.16% and 17-fold purification. The partially purified enzyme was strictly
      dependent on ATP and Mg2+ with optimal concentration of 1 and 10 mM respectively
      for relaxation activity. T. vaginalis DNA topoisomerase II activity was inhibited
      by m-amsacrine (m-AMSA) and ofloxacin at minimum inhibitory concentration (MIC)
      of 250 microM. At this concentration, ciprofloxacin showed incomplete inhibition
      whereas metronidazole was inactive. DW6, a DNA quadruplex binder, was the most
      active compound with MIC of 62.5 microM, suggesting the potential for development
      of such compounds as selective anti-trichomonal drugs in the future.

PMID- 19842368
TI  - Efficacy of contact lens solutions against Thai clinical isolates of
      Acanthamoeba.
AB  - Three clinical isolates of Acanthamoeba (A. castellanii, A. polyphaga, and A.
      mauritaniensis) were used to evaluate the cysticidal activity of four different
      contact lens multi-purpose solutions (Complete Protec, ReNu MultiPlus, Solocare
      Aqua, and Opti-free Aldox). Enumeration of amoebic was carried out with the
      control and test samples at 0, 2, 4, 6, 8, 10, and 24 hours after being added to
      the solutions using the most probable number (MPN) technique. A contact lens
      solution which achieved a 3-log reduction of Acanthamoeba during the
      manufacturer's minimum recommended disinfection time (MMRDT) was considered an
      effective solution. The studied contact lens solutions demonstrated decreasing
      number of amoebic with increasing exposure times, but were not effective against
      Acanthamoeba cysts during the MMRDT. Solocare Aqua gave the greatest reduction in
      A. castellanii (0.70-log reduction) and A. mauritaniensis (0.33-log reduction) by
      4 hours. Only Solocare Aqua caused a 3-log reduction in A. castellanii (3.02-log
      reduction) by 24 hours. Opti-free Aldox showed the greatest cysticidal activity
      against A. polyphaga (0.32-log reduction) by 6 hours, and gave the greatest
      reduction in A. mauritaniensis by 8, 10, and 24 hours.

PMID- 19842369
TI  - Cerebral venous sinus thrombosis in severe malaria.
AB  - Cerebral venous sinus thrombosis has been reported to be associated with various
      systemic illnesses and infections, including severe malaria. We report here a 43
      year-old Thai male presenting with fever and seizures. He was diagnosed as and
      treated for severe falciparum malaria. After gaining consciousness he developed
      focal neurological signs and evidence of increased intracranial pressure.
      Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the
      brain revealed a mid-superior sagittal sinus thrombosis with venous infarction.
      Investigations for other infections and thrombophilia were negative. The patient
      denied anticoagulant treatment. The clinical status and radiologic findings
      improved gradually. Physicians who care for malaria patients need to be aware of
      this rare complication when a malaria patient presents with focal neurological
      signs.

PMID- 19842370
TI  - In vivo antiparasitic activity of the Thai traditional medicine plant--Tinospora
      crispa--against Plasmodium yoelii.
AB  - We investigated the in vivo antimalarial effect of crude extract of Tinospora
      crispa, a Thai traditional medicine plant. Mice were inoculated with Plasmodium
      yoelii then treated with the crude extract of Tinospora crispa at doses of 20, 40
      and 80 mg/kg. Mice receiving the dose of 20 mg/kg died on average on Day 8. Mice
      remained alive longer when treated of the dose of 40 mg/kg or even longer under
      the treatment of the dose of 80 mg/kg. Surprisingly and interestingly, one mouse
      from the group in which the dose of 80 mg/kg was administrated is still alive and
      the parasite was cleared from the blood stream. In conclusion, T. crispa has an
      in vivo antimalarial effect in dose dependent manner.

PMID- 19842371
TI  - Digital malaria information sharing in Asia.
AB  - In 2001 a project named Mekong Malaria Documentation Center (MMDC) was
      established in Vietnam to support the information needs of malaria professionals
      in the Mekong Region. In 2005, MMDC was renamed and reorganized into a new
      database called ACTMalaria Information Resource Center (AIRC). AIRC's goal is to
      gather all published and unpublished materials, including electronic files,
      regarding malaria from ACTMalaria member countries. Today, there are eleven
      member nations. More than 1,500 files have been uploaded and are available for
      access. Various areas of AIRC still need to be developed, including editing,
      approvals of files, coordination with publishers, copyright issues, and the
      architecture of the database. Funding also needs to be secured for the
      sustainability of AIRC.

PMID- 19842372
TI  - DNA-based diagnosis of lymphatic filariasis.
AB  - Lymphatic filariasis (LF) is still a major public health problem. The disease is
      ranked by the World Health Organization (WHO) as the second leading cause of
      permanent and long-term disability, and has been targeted for elimination by
      2020. Effective diagnosis LF is required for treatment of infected individuals,
      for epidemiological assessment and for monitoring of the control program.
      Conventional diagnosis of LF depends on detection of microfilariae (Mf) in blood
      specimens, which has low sensitivity and specificity. Detection of specific
      circulating filarial antigens is regarded by WHO as the 'gold standard' for
      diagnosis of LF. However, the limitations of the antigen tests are cost and
      inconsistent availability. Although anti-filarial IgG4 antibody levels are
      associated with active LF infections, however, cross-reactivity with other
      filarial parasites is common. Not as sensitive as antigen tests, DNA-based
      techniques have been developed to diagnose and differentiate filarial parasites
      in humans, animal reservoir hosts, and mosquito vectors. These include DNA
      hybridization, polymerase chain reaction (PCR) amplification using specific
      primers (eg Ssp I repeat, pWb12 repeat, pWb-35 repeat, and LDR repeat for
      Wuchereria bancrofti and Hha I repeat, glutathione peroxidase gene, mitochondrial
      DNA for Brugia malayi), and universal primers, multiplex-PCR, PCR-restriction
      fragment length polymorphism (PCR-RFLP), PCR-enzyme linked immunosorbent assay
      (PCR-ELISA), as well as quantitative PCR. Furthermore, because bancroftian
      filariasis is endemic on the Thai-Myanmar border, the potential now exists for a
      re-emergence of bancroftian filariasis in Thailand, and random amplified
      polymorphic DNA (RAPD) analysis has proved effective to differentiate Thai and
      Myanmar strains of W. bancrofti.

PMID- 19842373
TI  - Dirofilaria causing eye infection in a patient from Malaysia.
AB  - Human dirofilariasis caused by Dirofilaria immitis and Dirofilaria repens have
      been reported in Malaysia. This is the fourth reported case of dirofilariasis
      caused by D. repens. The patient was a Chinese male from Kuching Sarawak,
      Malaysia who presented with a one day history of redness and itchiness over the
      temporal aspect of his left eye. A worm was seen and later removed from beneath
      the conjunctiva under local anesthesia and based on the morphological
      characteristics, it was identified as an immature Dirofilaria repens.

PMID- 19842374
TI  - Development of PCR-based diagnosis of minute intestinal fluke, Haplorchis
      taichui.
AB  - Haplorchis taichui specific primers were designed using a high annealing
      temperature random amplified polymorphic DNA (HAT-RAPD) PCR method and 18
      arbitrary primers (Operon Technologies) to generate polymorphic DNA profiles for
      13 different parasites. The H. taichui specific fragment was screened. A 256 bp
      HAT-RAPD marker generated from OPP-11 primer specific for H. taichui was cloned
      and sequenced. From the sequence data, specific primers were designed that
      generated a 256 bp amplicon. The minimum DNA template needed for PCR detection
      was 10 fg. The successful development of the H. taichui specific DNA-based
      detection will be beneficial in management and epidemiological control programs.

PMID- 19842375
TI  - Copro-diagnosis of Haplorchis taichui infection using sedimentation and PCR-based
      methods.
AB  - Fifty-one human fecal specimens were collected from villagers inhabiting along
      Mae Kuang River, Ban Sob Tha, Pa Sang District, Lamphun Province, Thailand. By
      the formalin-ether sedimentation technique (FEST) under a light microscope, eggs
      of 3 helminth species, Haplorchis taichui, Ascaris lumbricoides and unidentified
      hookworm species were detected with prevalences of 22, 14 and 4%, respectively.
      PCR amplification with H. taichui specific primers showed that H. taichui
      specific amplicon 260 bp was generated in all FEST-positive specimens, and also
      in some FEST negative specimens. This H. taichui specific PCR method can be used
      to detect this parasite in all developmental stages and in both definitive and
      intermediate hosts, which should be useful in prevention and control programs.

PMID- 19842376
TI  - Control of mosquito vectors of tropical infectious diseases: (3) susceptibility
      of Aedes aegypti to pyrethroid and mosquito coils.
AB  - We collected 11 groups of Aedes aegypti mosquitoes from various locations of
      Thailand. After rearing in the laboratory, the colonies were tested for KT50
      values to dl,d-T80-allethrin 0.5% mosquito coils in a 25 m3 room semi-field test
      and KD50 and LD50 values to dl,d-T80-allethrin by a topical application method.
      Two groups of mosquitoes were susceptible to allethrin similar to a SS (known
      allethrin sensitive) group, and other 9 groups showed various levels of lower
      susceptibility to allethrin; of these 6 had susceptibilities similar to a BS
      (known allethrin resistant) group with extremely low susceptibility, while the
      remaining 3 groups had susceptibilities to allethrin between the SS and BS
      groups. The KD50 values with the topical application were found to correlate
      highly with the KT50 values in the 25 m3 room semi-field test, providing a useful
      test method for insect susceptibility evaluation. The allethrin mosquito coils,
      even at higher concentrations, had no activity against the 6 decreased
      susceptibility groups, similar to the BS group. With the 25 m3 room semi-field
      test, mosquito coils with d,d-T-prallethrin at concentrations of 0.1 to 0.15%
      plus a synergist and those with methoxymethyl-tetrafluorobenzyl
      tetramethylcyclopropane carboxylate (K-3050) at a concentration of 0.1% plus a
      synergist were found to be highly effective against these mosquito groups. These
      two pyrethroids had smaller KD50 and LD50 values for topical application, and
      were more effective than dl,d-T80-allethrin, having the potential to control Ae.
      aegypti mosquitoes with low allethrin susceptibility.

PMID- 19842377
TI  - Scanning electron microscopy of the cibarial armature of species in the Anopheles
      dirus complex (Diptera: Culicidae).
AB  - The structure of the cibarial armature of mosquitoes has been found to be useful
      for taxonomic identification. We used a scanning electron micrograph to examine
      the cibarial armature of 4 of 5 species in the Anopheles dirus complex existing
      in Thailand: Anopheles dirus Peyton & Harrison, and An. cracens Sallum & Peyton,
      An. scanloni Sallum & Peyton, and An. baimaii Sallum & Peyton. In all species
      examined, there was only 1 row of large teeth or cones (modes = 12)
      characteristic of the Neomyzomyia series. The cones usually have anterior spines
      and a fimbriated or deeply cleft tip. No significant differences were observed
      among the 4 species examined, thus the cibarial armature has little value for
      taxonomic differentiation among these species. However, they appear different
      from closely related species in the Leucosphyrus complex reported previously.

PMID- 19842378
TI  - The effect of extrinsic incubation temperature on development of dengue serotype
      2 and 4 viruses in Aedes aegypti (L.).
AB  - Dengue 2 and 4 viruses obtained from dengue-infected patients were maintained in
      a C6/36 Aedes albopictus Skuse cell line and used to infect adult female Aedes
      aegypti mosquitoes. Each serotype was mixed separately with fresh human
      erythrocytes and fed to adult female mosquitoes using an artificial membrane
      feeding technique. Fully engorged mosquitoes were selected and retained at 26
      degrees C, 28 degrees C and 30 degrees C to observe dengue virus development in
      Aedes vectors. Virus detection was carried out by reverse-transcriptase
      polymerase chain reaction (RT-PCR). The virus was first detected on Day 9 at 26
      degrees C and 28 degrees C and on Day 5 at 30 degrees C for both dengue 2 and 4.
      The study shows the incubation period of the viruses decreased when the extrinsic
      incubation temperature increases.

PMID- 19842379
TI  - Outbreak of chikungunya fever in Thailand and virus detection in field population
      of vector mosquitoes, Aedes aegypti (L.) and Aedes albopictus Skuse (Diptera:
      Culicidae).
AB  - We investigated chikungunya fever outbreak in the southern part of Thailand.
      Human plasma specimens obtained from suspected patients and adult wild-caught
      mosquitoes were detected for chikungunya virus employing reverse transcriptase
      polymerase chain reaction technique. Chikungunya virus was detected in about half
      of the blood specimens whereas a range of 5.5 to 100% relative infection rate was
      found in both sexes of the vector mosquitoes, Aedes aegypti (L.) and Ae.
      albopictus Skuse. The infection rate in Ae. albopictus was higher than in Ae.
      aegypti, with relative infection rate in male of both species being higher than
      in female. The appearance of chikungunya virus in adult male mosquitoes of both
      species reveals a role of transovarial transmission of the virus in field
      population of the mosquito vectors. These findings have provided further
      understanding of the relationship among mosquito vectors, chikungunya virus and
      epidemiology of chikungunya fever in Thailand.

PMID- 19842380
TI  - Prevalence of hepatitis B and hepatitis C virus infections in potential blood
      donors in rural Cambodia.
AB  - The aims of the present study were to provide accurate prevalence of acute and
      occult hepatis B infection and hepatis C infection among potential blood donors
      in Cambodia and to study the accuracy of ELISA tests used for blood donor
      screening. A cross-sectional study was performed on samples collected from
      potential volunteer blood donors (n = 1,200) in two districts in rural Cambodia.
      The samples were tested using the ELISA technique for HBsAg, anti-HBc, and anti
      HCV at a local blood bank. To validate the ELISA outcomes, a subset (n = 319) was
      analyzed by Automated Chemiluminescent Microparticle Immunoassay Technique (CMIA)
      at the University Hospital North Norway. The overall prevalence of the HBsAg
      positives was 7.7% (95% CI 6.2-9.3); the prevalence of anti-HBc positive samples
      was 58.6% (95% CI 55.8-61.4), and the prevalence of anti-HCV positive samples was
      14.7% (95% CI 12.7-16.7). The prevalence rate of samples being both HBsAg
      positive and anti-HBc positive was 7.3% (95% CI 5.9 - 9.0), and the prevalence
      rate of HBsAg negative and anti-HBc positive samples was 51.2% (95% CI 48.4 -
      54.1). The overall agreement between the ELISA and the CMIA test results was very
      high both for HBsAg and anti-HBc (kappa 0.93), and high for anti-HCV measurements
      (kappa 0.83). However, the false-negative rate for the ELISA anti-HCV test was as
      high as 15% (95% CI 6 - 30).

PMID- 19842381
TI  - Priorities and challenges for hepatitis B control in the Philippines and the
      importance of a vaccine dose at birth.
AB  - The Philippines annual birth cohort of over 2 million is the second largest in
      the Western Pacific Region; 44% of births occur outside health facilities. With
      third dose infant hepatitis B (HB) vaccine coverage of 43% in 2006, erratic
      vaccine supply, and lack of policies or processes for universal HB vaccine birth
      dose delivery, a substantial burden of preventable chronic HB infection continues
      to occur. Funding, policy, technical and immunization delivery developments now
      make substantial progress in HB control in the Philippines possible. These
      developments can help expand access to trained birth care and essential postnatal
      care for mothers and their newborn.

PMID- 19842382
TI  - Reactogenicity and immunogenicity of a live-attenuated refrigerator-stable
      varicella vaccine (OKA strain) in healthy seronegative subjects age 10 months to
      12 years.
AB  - This study assessed the immunogenicity and reactogenicity of a live-attenuated
      varicella vaccine (Oka strain), Varilrix in Indonesian children age 10 months to
      12 years. A total of 300 seronegative subjects were stratified into three age
      subgroups (10 months to < 3 years, 3 years to < 7 years and 7 to 12 years) and
      all received a single-dose of Oka strain varicella vaccine. One solicited local
      symptom (injection site soreness) was reported during the 43-day post-vaccination
      follow-up period. Fever (29/295; 10%) was more prevalent than rash (3/295; 1%)
      but the incidence of grade 3 fever (defined as axillary temperature of >39
      degrees C) was infrequent. No grade 3 unsolicited events and no serious adverse
      events were reported. The vaccine proved to be immunogenic in all age groups; all
      but one subject seroconverted for anti-varicella antibodies 43-days post
      vaccination. This study demonstrated that the live-attenuated varicella vaccine
      (Oka strain) was well tolerated and immunogenic with no safety issues when
      administered as a single dose primary vaccination to healthy, seronegative
      Indonesian subjects age 10 months to 12 years.

PMID- 19842383
TI  - Multidrug-resistant TB and HIV in Thailand: overlapping, but not independently
      associated, risk factors.
AB  - The HIV and multi-drug resistant tuberculosis (MDR-TB) epidemics are closely
      linked. In Thailand as part of a sentinel surveillance system, we collected data
      prospectively about pulmonary TB cases treated in public clinics. A subset of HIV
      infected TB patients identified through this system had additional data collected
      for a research study. We conducted multivariate analysis to identify factors
      associated with MDR-TB. Of 10,428 TB patients, 2,376 (23%) were HIV-infected; 145
      (1%) had MDR-TB. Of the MDR-TB cases, 52 (37%) were HIV-infected. Independent
      risk factors for MDR-TB included age 18-29 years old, male sex, and previous TB
      treatment, but not HIV infection. Among new patients, having an injection drug
      use history was a risk factor for MDR-TB. Of 539 HIV-infected TB patients in the
      research study, MDR-TB was diagnosed in 19 (4%); the only significant risk
      factors were previous TB treatment and previous hepatitis. In Thailand, HIV is
      common among MDR-TB patients, but is not an independent risk factor for MDR-TB.
      Populations at high risk for HIV-young adults, men, injection drug users - should
      be prioritized for drug susceptibility testing.

PMID- 19842384
TI  - Distribution and sequence analysis of virulence associated genes in Vibrio
      cholerae O1, O139 and non-O1/non-O139 isolates from Thailand.
AB  - Virulence-associated genes of Vibrio cholerae including O1, O139 and non-O1/non
      O139 from an outbreak in Songkhla Province and sporadic cases occurred in
      Thailand during 1993 - 2002 were investigated. One hundred eighty-five V.
      cholerae strains were examined for the presence of virulence-associated genes
      including ctxA, tcpA, zot, toxR, toxS, toxT, and ace by polymerase chain
      reaction. DNA sequences of ctxA, tcpA, zot and toxR also were investigated in 8
      selected isolates. Results showed that the virulence factors genes were
      distributed in the majority of V cholerae O1 biotype Inaba and Ogawa strains (85
      97%). All 6 strains of the O139 harbored toxR, toxS and toxT whereas ctxA, tcpA,
      zot and ace were detected only 50-67%. Toxins genes found in non-O1/non-O139
      strains ranged 8-30% except toxR (73.5%). Results of multiple sequence alignments
      among the isolates compared with V. cholerae O1 in database (embl M21249), showed
      that ctxA, tcpA and zot sequences in all 8 isolates were conserved, but base
      changes were found in toxR sequence. These molecular characteristics of V
      cholerae isolated from Thailand will provide detailed information for
      facilitating future studies on the development and design of appropriate vaccine
      providing protection against local strains.

PMID- 19842385
TI  - In vitro antimicrobial activity of Ocimum americanum L. essential oil against
      oral microorganisms.
AB  - The aim of the present study was to evaluate the efficacy of the essential oil of
      Ocimum americanum L. on in vitro activity against Streptococcus mutans,
      Lactobacillus casei and Candida albicans. An agar disk diffusion method was
      employed for screening antimicrobial activity. Minimum inhibitory concentration
      (MIC) and minimum cidal concentration (MCC) values of the oil against planktonic
      cells were determined using the Millipore membrane method. The antimicrobial
      potential of the essential oil was also investigated with a biofilm model. The
      results indicate that essential oil has antimicrobial activity against all tested
      microorganisms. The MIC values of the oil against the three organisms was 0.04%
      v/v whereas the MCC values for S. mutans, L. casei and C. albicans were 0.08%,
      0.3% and 0.08% v/v, respectively. S. mutans and C. albicans were more sensitive
      to the essential oil than L. casei. With the biofilm assay, a 5-minute exposure
      to 3% v/v essential oil eliminated 3 logo10 of the tested microorganisms. At a
      lower concentration (0.3% v/v), a 2 log10 reduction in S. mutans and C. albicans
      was observed while the lactobacilli were more resistant. This finding indicates
      the possibility of using the essential oil of O. americanum L. in oral health
      care products for reducing these pathogenic microorganisms in the oral cavity.

PMID- 19842386
TI  - Cerebellar cryptococcoma in an immunocompetent adult patient.
AB  - Isolated cerebellar cryptococcoma in an immunocompetent patient is a rare
      condition. We report a case of an immunocompetent adult with isolated cerebellar
      cryptococcoma. The patient presented with chronic headaches for one year and was
      found to have multiple cerebellar abscesses on imaging. Our patient underwent
      resection of the lesion and the cryptococcoma was subsequently diagnosed by
      histological examination. We initiated treatment with antifungal medicine and was
      successfully treated after 6 months of therapy. A cryptococcoma may be a cause of
      isolated cerebellar abscess in immunocompetent patients despite not finding
      cryptococcal antigen in the serum.

PMID- 19842387
TI  - The prevalence of sexually transmitted and other lower reproductive tract
      infections among rural women in Sichuan Province, China.
AB  - To estimate the prevalence of sexually transmitted infections (STI) and lower
      reproductive tract infections (RTI) and determine risk factors for STI among
      rural women in Sichuan Province, China, a cross-sectional, community-based
      cluster sample of 2,000 rural, married women were interviewed, examined and
      clinical specimens collected to assess for six STI and two non-sexually
      transmitted RTI. The overall prevalence of any STI was 10.9% (95% CI 9.5-12.3);
      of any STI or RTI was 30.8% (95% CI 28.7-32.8). Chlamydia trachomatis was
      detected in 6.4% of women, Neisseria gonorrhoeae in 1.7%, Treponema pallidum in
      0.5%, human papilloma virus in 0.6%, herpes simplex virus type-2 in 2.0%, Candida
      albicans in 8.8%, Trichomonas vaginalis in 0.7% and bacterial vaginosis in 15.4%.
      The reported low risk sexual behavior was corroborated by the prevalence of
      STIbased on laboratory findings. The prevalence of Chlamydia trachomatis alone
      and the combined prevalence rates of Neisseria gonorrhoeae and Chlamydia
      trachomatis were high enough (7.9%) to consider interventions for the control of
      cervical infections. Health promotion messages regarding safe sexual and health
      care seeking behavior is important. Routine STI surveillance, including
      prevalence studies, which provide accurate information for decision-making should
      be continued as an essential component of good STI control.

PMID- 19842388
TI  - Knowledge, attitudes, and acceptability of a human papillomavirus vaccine among
      healthcare providers.
AB  - A cross-sectional survey was conducted to evaluate acceptability, knowledge, and
      attitude regarding HPV, cervical cancer, and HPV vaccine among healthcare
      providers working in hospitals located in Bangkok, Thailand. Two hundred nurses
      and 100 doctors from three government hospitals and one private hospital were
      recruited. Data collection was done using a self-administered questionnaire.
      Nurses and doctors knowledge on HPV, cervical cancer, and HPV vaccine was at a
      medium level. Both nurses and doctors had positive attitude toward HPV, cervical
      cancer, and HPV vaccine. Approximately 80% of nurses and 63% of doctors agreed on
      the use of a HPV vaccination. Almost all the nurses and doctors suggested that
      adolescent aged < or = 18-years-old should be the target group for HPV
      vaccination. Furthermore, 73% of nurses and 76% of doctors would recommend
      clients to receive HPV vaccine.

PMID- 19842389
TI  - Factors influencing married youths' decisions on contraceptive use in a rural
      area of Myanmar.
AB  - This study aimed to describe the factors influencing the decision of married
      female youth and their husbands measured by self-rating on the magnitude and
      importance of each factor and person, and agreement between willingness to use
      and actual contraceptive use. A community-based cross-sectional study was
      conducted in Ayeyarwaddy Division, Myanmar. The decision to use contraception
      increased significantly due to motivation from a provider, friends, spousal
      communication, and benefits of contraception by multiple logistic regression.
      Influencing factors which attained the magnitude of >50% and importance of >5
      scores for their decision were a couple's attitude, spousal communication,
      pregnancy susceptibility, couple's knowledge, and benefit of contraception. A
      fair agreement was found between willingness to use and actual use.

PMID- 19842390
TI  - High-dose intravenous dexamethasone in the management of diarrheal patients with
      enteric fever and encephalopathy.
AB  - We conducted a retrospective chart analysis of diarrheal patients with enteric
      fever and encephalopathy (among survivors and non-survivors) to examine the role
      of high-dose, intravenous dexamethasone as an adjunct to appropriate
      antimicrobial therapy in their management. We studied all patients admitted to
      the Special Care Ward (SCW) of Dhaka Hospital between October 2006 and October
      2007 with a diagnosis of encephalopathy in association with enteric fever. Twenty
      three cases were identified with three mortalities. All bacterial isolates
      (Salmonella Typhi and Salmonella Paratyphi) were multi-drug resistant. Survivors
      were significantly more likely to have received high dose dexamethasone (100% vs
      00%; p < 0.001) and had hypoglycemia less often (6% vs 67%; p = 0.045) compared
      to those who died. The results suggest high dose intravenous dexamethasone, as an
      adjunct to appropriate antimicrobial therapy, substantially reduces mortality
      among diarrheal patients presenting with enteric encephalopathy.

PMID- 19842391
TI  - Quality indicators of diabetes care in practice.
AB  - The objective of this study was to explore the practicability of using process
      and outcome indicators to routinely assess the quality of diabetes care. Health
      care data of diabetic patients using antidiabetic drugs older than 40 years old
      in 2006-2008 were retrieved from an electronic information system of
      Phramongkutklao Hospital, Thailand. The process and outcome indicators were taken
      from the standard of medical care in diabetes of the American Diabetes
      Association, 2006 - 2008 and other studies. A list of the practical indicators
      was selected according to the availability and completeness of the electronic
      data in the information system, consisting of glycemic control, lipid control,
      and antiplatelet therapy. For process indicators, the percentages of patients
      with a yearly measured HbAlc, LDL-cholesterol, triglyceride, HDL-cholesterol, and
      antiplatelet therapy were 56.5-67.2, 87.8-90.2, 76.6-81.4, 71.8-75.5, and 69.7
      75.9%, respectively. For outcome indicators, the percentages of patients with
      most recent blood levels of HbAlc, LDL-cholesterol, triglyceride, and HDL
      cholesterol at target levels were 25.1-32.5, 27.7-33.9, 50.1-54.7, and 53.1
      62.5%, respectively. The practicability of these quality indicators in
      determining the quality of diabetes care will depend on the quality of the
      hospital electronic databases. Among these applicable indicators at this
      particular setting, the glycemic and lipid control, and antiplatelet therapy
      seemed to be sufficiently provided according to the standard diabetes care
      recommendation. However, the poor outcomes as measured by lipid profiles and
      HbAlc suggested that other intervention may also be necessitated to better these
      outcomes.

PMID- 19842392
TI  - Postprandial osmolality of gastric contents in very low-birth-weight infants fed
      expressed breast milk with additives.
AB  - The objective of the study was to evaluate the effect of each additive [FeSO4,
      multivitamin (MTV), and vitamin E] on the postprandial osmolality of expressed
      breast milk (EBM) at 0, 30, 45 and 60 minutes. Babies born at Songklanagarind
      Hospital from 1 August, 2005 to 31 December, 2006 were studied; EBM was collected
      from mothers with a child born at an estimated gestational age less than 32 weeks
      or whose babies had a birth weight less than 1,500 grams. The volume of EBM
      depended on daily needs. The osmolality was determined by the additives in the
      EBM both before and after administration of each additive and in the gastric
      contents after gavage feeding at 0, 30, 45 and 60 minutes. Twenty-six infants
      were enrolled in the study. The median postprandial osmolality of EBM with MTV at
      0, 30, 45 and 60 minutes were 413, 386.5, 388 and 383 mOsm/kg, respectively. At
      no time was the osmolality of FeSO4 or vitamin E-mixed EBM above 400 mOsm/kg.

PMID- 19842393
TI  - Analysis of blood donor deferral characteristics in Delhi, India.
AB  - Blood donors are deferred from donating blood for several reasons, either
      permanently or temporarily. Losses related to disease marker rates are well
      established. Donor and donation losses for other reasons, however, have not been
      extensively quantified. This study quantified the rate of and reasons for donor
      deferral among Delhi donors. A retrospective study was conducted by reviewing the
      deferral donor records from 1 January 2007 to 31 December 2008. The percentage of
      deferred donors was 9% with majority of them (91.0%) being deferred for temporary
      reasons. Anemia was the most frequent cause for donor rejection (32.8%).
      Permanent deferral accounted for 9.1% with hypertension being the most common
      cause (29.4%) in this category.

PMID- 19842394
TI  - Autonomous public organization policy: a case study for the health sector in
      Thailand.
AB  - This paper describes factors affecting autonomous public organization (APO)
      policy agenda setting and policy formation through comparison of policy processes
      applied to one educational institute under the Ministry of Education and the
      other educational institute under the Ministry of Public Health in Thailand. This
      study employs mixed method including a qualitative approach through documentary
      research, in-depth interviews, and participant observation. Factors that
      facilitated the formulation of the APO policy were: (1) awareness of need; (2)
      clarity of strategies; (3) leadership, advocacy, and strategic partnerships, (4)
      clear organizational identity; (5) participatory approach to policy formulation,
      and (6) identification of a policy window. Factors that impeded the formulation
      of the APO policy were: (1) diverting political priorities; (2) ill-defined
      organizational identity; (3) fluctuating leadership direction, (4) inadequate
      participation of stakeholders; and (5) political instability. Although findings
      cannot be generalized, this case study does offer benchmarking for those in
      search of ways to enhance processes of policy formulation.

PMID- 19842395
TI  - Quality analysis of commercial probiotic products for food animals.
AB  - Thirteen commercial probiotic feed products were examined for microbiological
      content and the results were compared with the information available on the
      product labels. Antibiotic resistance of Lactobacillus and Bacillus was
      investigated. All the products were inaccurately labelled in either numbers or
      species of bacteria. Misnaming at the species level was the most common flaw.
      Lactobacillus exhibited higher-antibiotic resistance than Bacillus did. Plasmid
      was found in both Lactobacillus (22%) and Bacillus (2.5%). The vanA gene was
      present in one L. plantarum and one B. subtilis isolate. The vanA-containing B.
      subtilis also harbored the tetW gene. None of the genes detected appeared to be
      associated with a conjugative plasmid.

PMID- 19842396
TI  - Evaluation of an electronic air filter for filtrating bacteria and viruses from
      indoor air.
AB  - This study compared the filtrating efficiency (FE) of a commercial electronic air
      filter for filtering bacteria and viruses from contaminated air with a high
      efficiency particulate air (HEPA) filter. An enclosed chamber was constructed, in
      the middle of which an air filter was placed for testing. MTB H37Ra and T7 virus
      at concentrations of 5x10(8) each were sprayed into one side of the chamber using
      a nebulizer and the sprayed samples were collected by an impinger air-sampler on
      the other side. MTB and T7 viruses were detected by PCR and culture. The PCR
      could detect samples down to 10 fg for MTB H37Ra and 1 pg for T7 virus. Most MTB
      H37Ra sprayed failed to culture. S. aureus at a concentration of 10(5) cfu and E.
      coli at a concentration of 10(4) cfu along with T7 virus were filtered out with a
      FE of more than 99%. T7 virus has a particle size of 0.04 microm, S. aureus has a
      particle size of 1 microm and E. coli has a particle size of 2 microm.

PMID- 19842397
TI  - Histopathological alterations of the gills, liver and kidneys in Anabas
      testudineus (Bloch) fish living in an unused lignite mine, Li District, Lamphun
      Province, Thailand.
AB  - The acidity of mine water generally makes it toxic to most organisms. The gills,
      kidneys and livers of Anabas testudineus Bloch fish inhabiting the acidic water
      (pH 2-4) of an unused lignite mine in Li District, Lamphun Province, Thailand
      were examined and compared to those of farmed fish. Tissue abnormalities were
      found in all investigated organs. Deterioration and telangiectasia of gill
      filaments were found. Liver tissue revealed hemorrhages, blood congestion and
      necrotic cells with mononuclear cell infiltration. In addition, hypertrophy of
      the epithelial cells of the renal tubules with reduced lumens, aneurisms of the
      renal tubules, and contractions of the glomeruli in the Bowman's capsule were
      observed. These histopathological findings suggest the acidic water in this
      habitat causes severe damage to the internal organs of fish and consequently
      alter their physiological status. Since the water in this pond is utilized by
      local people, these findings highlight the need for adequate water treatment.

PMID- 19842398
TI  - Blood stage Plasmodium falciparum antigens induce immunoglobulin class switching
      in human enriched B cell culture.
AB  - This study aimed to demonstrate class switch recombination (CSR) in heavy chain
      expressing immunoglobulin G (IgG) and IgE in human B cells after exposure to
      Plasmodium falciparum schizont lysate. Human B cells (CD20+CD27-) were cultured
      with crude P. falciparum antigen (cPfAg) and anti-CD40. On Day 4 post-exposure,
      total RNA from B cells was prepared and the occurrence of CSR from IgM to IgG
      and/or IgE was investigated by reverse transcription-polymerase chain reaction.
      Molecular markers to detect active CSR included enzyme activation-induced
      cytidine deaminase mRNA, gamma and epsilon-germline transcripts (gamma, epsilon
      GLT), circle transcript (CT) and mature transcript (gamma and epsilon-mRNA)
      expression. On Day 7 and Day 14 after exposure, levels of Igs in the culture
      supernatant were determined by enzyme-linked immunosorbent assay. Our findings
      showed that we could demonstrate cPfAg-stimulated B cells undergoing CSR by use
      of the expressed CSR markers and the increase in specific IgG and IgE indicating
      the potential of this approach in the study of CSR in P. falciparum-stimulated B
      cells.

PMID- 19842399
TI  - Prevalence of clinical malaria among an Orang Asli community in Malaysia.
AB  - An epidemiological cross-sectional study was undertaken to determine the
      prevalence of clinical malaria among the Orang Asli population of Raub, Pahang,
      Malaysia. The study was conducted on a representative sample of 520 Orang Asli.
      Malariometric and clinical measurements were taken. The overall parasitemic rate
      was 24.2% (95% CI 20.7-28.1). Twenty-three point four percent (95% CI 19.5-26.9)
      of respondents age two years and above were clinically febrile. The prevalence of
      fever, chills, perspiration and body aches during a one month period prior to the
      survey among the same group ranged between 4.2% (95% CI 2.7-6.4) and 13.5% (95%
      CI 10.6-16.7). Children 2-12 years old were more likely to present with fever,
      and symptoms of malaria than older children. Gender was not significantly
      associated with fever or any of the other malaria symptoms. Presence of clinical
      fever and history of malaria symptoms were all strongly associated with current
      infection. The association was significant even after controlling for age
      (adjusted OR 2.8-5.1, 95% CI 1.1-8.3). Orang Asli children significantly
      experienced greater morbidity due to malaria compared to adults. Control and
      treatment of malaria should focus on children, while further research should
      explore the effects of malaria morbidity on the quality of life of these
      children.

PMID- 19842400
TI  - Malaria trends and challenges in the Greater Mekong Subregion.
AB  - This report provides an overview of the epidemiological patterns of malaria in
      the Greater Mekong Subregion (GMS) from 1998 to 2007, and highlights critical
      challenges facing national malaria control programs and partners in effort to
      build on their successes as they move towards malaria pre-elimination and
      elimination as a programmatic goal. Epidemiological data provided by malaria
      programs show a drastic decline in malaria deaths and confirmed malaria positive
      cases over the last 10 years in the GMS. More than half of confirmed malaria
      cases and deaths recorded in the GMS occur in Myanmar, however, reporting methods
      and data management are not comparable between countries despite effort made by
      WHO to harmonize data collection, analysis and reporting among WHO Member States.
      Malaria is concentrated in forested/forest-fringe areas of the region mainly
      along international borders providing strong rationale to develop harmonized
      cross-border pre-elimination programs in conjunction with national efforts.
      Across the Mekong Region, the declining efficacy of recommended first-line
      antimalarials, eg artemisinin-based combination therapies (ACTs) against
      falciparum malaria on the Cambodia-Thailand border, the prevalence of counterfeit
      and substandard antimalarial drugs, the lack of health services in general and
      malaria services in particular in remote settings, and the lack of information
      and services targeting migrants and mobile population present important barriers
      to reach or maintain malaria pre-elimination programmatic goals. Strengthening
      networking between research institutions and non-government organizations will
      increase knowledge-based decision and action.

PMID- 19842401
TI  - Heterologous production of dense granule GRA7 antigen of Toxoplasma gondii in
      Escherichia coli.
AB  - Infection with Toxoplasma gondii causes serious health problems in congenitally
      infected and immunocompromised individuals. Numerous studies have shown
      usefulness of dense granule antigens of T. gondii in serodiagnosis of the
      infection and induction of protective immunity. This study describes cloning,
      expression, purification and antigenicity evaluation of recombinant GRA7 protein
      (rGRA7). DNA encoding GRA7, amino acids 18 to 236, was obtained from Toxoplasma
      gondii RH strain by polymerase chain reaction amplification and cloned in
      prokaryotic expression plasmid pET-28b(+). Sequence analysis showed 97%
      similarity between GRA7 gene fragment and published sequence of gra7. Recombinant
      protein was expressed in Escherichia coli and purified in a single step by
      immobilized metal ion affinity chromatography. Antigenicity of the protein was
      evaluated in Western blot analysis showing human sera from acute T. gondii
      infection strongly reacted with rGRA7 while sera from chronic infection weakly
      recognized the protein. Negative sera failed to react with rGRA7. The antigenic
      rGRA7 might be used, in combination with other T. gondii antigen, to develop more
      efficacious diagnostic tests and/or in vaccine formulations.

PMID- 19842402
TI  - Genes and cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a major public health problem in the northeastern
      part of Thailand where the prevalence of this cancer is highest in the world. It
      is a slow growing tumor but highly metastatic with a poor prognosis. The
      traditional habit of eating raw fish, repeated exposure to liver fluke and
      consumption of nitrosamine-contaminated food are major risk factors.
      Understanding of carcinogenesis and metastasis of cholangiocarcinoma at the
      molecular level will provide tools for better prevention, diagnosis and
      treatment. This review focuses on CCA- associated genes and their possible
      applications.

PMID- 19842403
TI  - Vectorial role of Anopheles subpictus Grassi and Anopheles culicifacies Giles in
      Angul District, Orissa, India.
AB  - Malaria transmission by Anopheles subpictus Grassi, 1899 and Anopheles
      culicifacies Giles, 1901 was studied from March 2004 to February 2007 in Angul
      District, Orissa, India, which is highly endemic for malaria. Adult mosquitoes
      were collected from human dwellings using sucking tubes and a mechanical
      aspirator. After identification, some An. subpictus and An. culicifacies
      specimens were subjected to a precipitin test to determine their anthropophilic
      index and the remaining samples were preserved in isopropyl alcohol for
      sporozoite detection by nested PCR. An. subpictus was the most prevalent (29.0%)
      anopheline species detected, followed by An. culicifacies (11.6%). The
      anthropophilic index for the An. subpictus was higher than An. culicifacies and
      was highest during the summer season. Malaria sporozoite rates of 0.52% and 1.82%
      were detected for An. subpictus and An. culicifacies, respectively. Sporozoites
      were detected during the summer in An. subpictus and during the rainy season and
      winter in An. culicifacies. The slide positivity rate (SPR) was high during the
      summer. The high anthropophilic index and presence of sporozoites in An.
      subpictus during the summer indicate An. subpictus is a contributory factor for
      the high SPR during the summer, and An. culicifacies is a contributory factor for
      the high SPR during the rainy and winter seasons, along with other anophelines.
      In the present study An. subpictus has been incriminated as a vector of malaria
      for the first time in Orissa.

PMID- 19842404
TI  - Mosquito fauna of "Toh Daeng" swamp forest, Thailand.
AB  - Entomological surveys (2001-2005) were carried out in Narathiwat Province to
      determine mosquito fauna of the peat swamp forest. Fifty-four species belonging
      to 13 genera were identified from 837 larval specimens and 3,982 adult
      mosquitoes. These included the major vectors for Brugian fillariasis: Mansonia
      annulata, Ma. bonneae, Ma. dives, Ma. uniformis and Ma. indiana. Ma. annulata and
      An. letifer were reported for the first time in Thailand as lymphatic filariasis
      vectors. Three species inhabiting Nepenthes pitchers (N. mirabilis): Tripteroides
      tenax, Toxorhynchites manopi and Uranotaenia edwardsi, were recorded for the
      first time in Thailand; Zeugnomyia gracilis was also found common in the peat
      swamp forest.

PMID- 19842406
TI  - Etiology of enterically-transmitted hepatitis among foreigners in Nepal.
AB  - We report the etiology of hepatitis in travelers over a ten year period from
      January 1994 December 2003. Clinics catering to expatriates and tourists in
      endemic Nepal provided sera for diagnostic testing from persons with signs and
      symptoms compatible with clinical hepatitis and alanine transaminase levels 2 1/2
      times greater than normal. Hepatitis E was determined with anti-HEV IgM, and HEV
      RT-PCR, and hepatitis A was determined using HAV-IgM. Thirty-seven cases of
      hepatitis A and 30 cases of hepatitis E were diagnosed during the study period.
      The frequency of hepatitis A cases decreased with the increasing use of hepatitis
      A vaccine while the frequency of hepatitis E cases remained stable. A hepatitis E
      vaccine would be of benefit for travelers to high to high risk areas.

PMID- 19842405
TI  - Cardiac involvement in dengue virus infections during the 2004/2005 dengue fever
      season in Sri Lanka.
AB  - Sri Lanka experienced a dramatic increase in dengue cases (15,400) in the 2004 -
      2005 season. We carried out a prospective study to investigate cardiac
      involvement in dengue virus infected patients during the 2004 - 2005 season in
      Peradeniya, Central Province, Sri Lanka. Cardiac involvement was defined as
      elevated levels of myoglobin, creatine kinase-muscle brain-type, N-terminal pro
      brain natriuretic peptide, heart-type fatty acid-binding protein and troponin T.
      Twenty-five percent of dengue virus infected patients had one or more of the
      above tests with abnormal results.

PMID- 19842407
TI  - Febrile period and maximum body temperature in patients with measles over 15
      years old.
AB  - The medical records of Japanese patients with measles, age 15 to 39 years old,
      were analyzed for febrile period in 200 patients and maximum body temperature in
      211 patients. The febrile periods by age group were as follows: 7.7 +/- 1.4 days,
      7.8 +/- 1.7 days, 8.1 +/- 1.7 days, 8.1 +/- 2.4 days and 7.5 +/- 1.4 days in 15
      19, 20-24, 25-29, 30-34 and 35-39 year-olds, respectively. No significant
      differences in febrile periods were identified among the different age groups. A
      maximum body temperature over 40 degrees C was seen in 61, 58, 59, 50 and 33% of
      the 15-19, 20-24, 25-29, 30-34 and 35-39 year-olds, respectively. The results of
      our study indicate age is not a determining factor for febrile period, but
      maximum body temperature may be lower in older than in younger patients with
      measles.

PMID- 19842408
TI  - Impact of a measles elimination strategy on measles incidence in Malaysia.
AB  - In Malaysia, the two dose measles - mumps - rubella (MMR) vaccine was introduced
      in the Expanded Program on Immunization in 2002. The Ministry of Health then
      initiated a measles elimination strategy which included enhanced case-based
      surveillance with laboratory testing of all suspected cases. The objective of our
      study was to analyse national measles laboratory data from 2004 to 2008 to study
      the impact of the nationwide strategy on measles case incidence. Blood samples
      collected from suspected measles cases during the acute stage of the illness were
      investigated for measles specific IgM. The estimated incidence of measles ranged
      from 22.3 cases (in 2004) to 2.27 cases (in 2006) per 100,000 population. During
      this time, the measles vaccination coverage was above 85%. Laboratory confirmed
      measles cases dropped from 42.2% in 2004, when sporadic outbreaks were reported,
      to 3.9% in 2007. Screening for measles IgG levels in 2008 showed that 82.8% of
      those > 7 years old had adequate immunity. The measles control strategy appears
      to have been successful in reducing the incidence of measles. Continuing high
      vaccination coverage rates and ongoing measles surveillance are necessary to
      achieve our goal of measles elimination.

PMID- 19842409
TI  - HIV-1 subtype B Tat gene activities and disease progression in HIV-1 CRF01_AE
      infection.
AB  - HIV-1 tat gene function and immunogenicity of HIV-1 Tat protein from 3 low (PS01,
      PS40, PS58) and 3 high (PS19, PS65, LP22) viral load infected, untreated and
      asymptomatic individuals from Thailand were compared. Levels of Tat-dependent
      chloramphenicol acetyltransferase (CAT) induced in HL3T1 cells with tat1 gene
      from HIV-1 isolates of high viral load group was significantly higher than those
      from low viral load group. HIV-1 subtype determination using env (C2-V4) gene
      demonstrated that 2/3 (PS01 and PS40) and 1/3 (PS58) from low viral load group
      were CRF01_AE and subtype B, while all 3 HIV-1 isolates from high viral load
      group were CRF01_AE. However, all 3 HIV-1 tat nucleotide sequences from low viral
      load group, which contained env CRF01_AE sequence, belonged to subtype B whereas
      all those from high viral load group contained CRF01_AE sequence. HIV Tat
      recombinant proteins from these groups were tested for immunogenicity in mice.
      All recombinant Tat proteins (except from PS58) were immunogenic in a dose
      dependent manner, but with significantly differences of the immunogenicity levels
      between high and low viral load groups. These results indicated that HIV-1
      subtype B tat gene activities might be associated with reduced disease
      progression of HIV-1 CRF01_AE infected individuals.

PMID- 19842410
TI  - Cytomegalovirus glycoprotein B gene polymorphism and its association with
      clinical presentations in infants.
AB  - The clinical manifestations in cytomegalovirus infected-infants vary from
      asymptomatic illness to highly fatal cytomegalic inclusion disease. The influence
      of human cytomegalovirus (HCMV) strains on the outcome of HCMV disease is poorly
      explored. The present study was undertaken to explore the role of gB genotypes
      with clinical features in infants with clinically suspected HCMV disease. Urine
      samples of 71 infants (age < 1 year) with clinically suspected HCMV disease were
      subjected to amplification of glycoprotein B (gB) gene by polymerase chain
      reaction (PCR) followed by restriction fragment length polymorphism using RsaI
      and HinfI. HCMV DNA could be detected in 12 samples by gB gene PCR, 6 of which
      comprised of gB2, followed by gB1 in 5 samples and gB3 in 1 sample. Organomegaly
      was the most common finding (67%) followed by jaundice (50%), pneumonia (50%),
      seizures (42%), microcephaly (25%), low birth weight (25%) and rashes (17%). No
      particular genotype was significantly associated with specific clinical
      presentation or organ system involvement.

PMID- 19842411
TI  - Comparative evaluation of two cold staining methods with the Ziehl-Neelsen method
      for the diagnosis of tuberculosis.
AB  - In developing countries pulmonary tuberculosis is usually diagnosed by detecting
      acid-fast bacilli (AFB) in sputum using a Ziehl-Neelsen (Z-N) staining method.
      However, in the field the traditional method of staining is difficult to carry
      out. This study evaluates the efficiency of two cold staining methods, namely
      Gabbet's and a modified two reagent cold staining method compared with the Z-N
      taken as the gold standard. Triplicate smears were prepared from 267 sputum
      samples and stained by the Z-N, Gabbet's, and a modified cold staining method,
      the smears were positive for AFB in 21 (7.87%), 18 (6.74%) and 19 (7.12%),
      respectively. The sensitivities for the Gabbet's and modified cold stain were
      85.7% and 90.5%, respectively. The positive agreement between the Z-N and
      Gabbet's (92.3%) and Z-N and modified cold stain (95%) were good. The modified
      cold staining method was less time consuming and easier to perform in the field.

PMID- 19842412
TI  - Osteoarticular tuberculosis: how often is it missed?
AB  - This study was carried out to analyze the clinical presentations and outcomes of
      osteoarticular tuberculosis (OAT) at a university hospital in AlKhobar, Saudi
      Arabia. A prospective observational study was carried out between 1 January 1998
      and 31 December 2007. Patients demographic characteristics were recorded,
      including age, gender, nationality, clinical manifestation, delay in diagnosis,
      laboratory results, findings on imaging studies, histological and bacteriological
      studies of biopsy specimens, treatment modalities, surgical interventions and
      final outcomes. Fifty-two patients were diagnosed with OAT during the study
      period. The majority were males (64%), about half were below age 30 years. The
      mean age at diagnosis was 33 years. There were 32 Saudis (64%), and 18 non-Saudis
      (36%). Pyrexia, loss of appetite and night sweats were the presenting symptoms in
      44, 38 and 36%, respectively. The average time from onset of symptoms to
      diagnosis was 185 days (7-730 days). On admission, the average erythrocyte
      sedimentation rate (ESR) was 68 mm/h (4-142). A Mantoux test was performed, in 48
      patients the results were positive. The vertebral column was the site of
      infection in 88% of patients. All patients were managed with standard
      antituberculous therapy. Forty-two patients (84%) had a favorable outcome.

PMID- 19842413
TI  - Empyema thoracis due to nocardiosis and Mycobacterium tuberculosis mixed
      infections in an AIDS patient.
AB  - A 26-year-old Thai man presented with progressive dyspnea for four months and
      right pleuritic chest pain two days before admission. The chest radiograph showed
      massive right pleural effusion. Thoracentesis was done, and the culture grew
      Nocardia spp as well as positive strain for acid-fast bacilli. An anti-HIV test
      was reactive, with a CD4 count of 12 cells/mm3. The patient was treated with
      inter-costal tube drainage (ICD) inserted for empyema thoracis. The
      antimicrobials used trimethoprim-sulfamethoxazole and anti-TB drugs CAT-1 orally.
      One month later, anti-retroviral therapy with HAART was initiated. At follow-up
      after 6 months, he was healthy appearing, with a nearly normal chest radiograph.

PMID- 19842414
TI  - Lack of correlation of Burkholderia pseudomallei quantities in blood, urine,
      sputum and pus.
AB  - We evaluated the correlation of Burkholderia pseudomallei quantities in blood
      versus urine, sputum or pus. Correlations between bacterial counts in blood and
      other samples were not found. It is likely that an initial seeding event to
      extracellular organs is followed by independent growth of B. pseudomallei, and
      that bacteria in the urine were not passively filtered from the bloodstream.

PMID- 19842415
TI  - Endemic typhus (murine typhus) in an 18 year old Libyan adult.
AB  - We present a case of an 18 year old Libyan with a history of fever, frontal
      headache, bodyache, malaise, abdominal pain, nausea and vomiting, followed by
      macular to maculopapular rash. A diagnosis of endemic typhus (murine typhus) was
      made based on the typical clinical findings and epidemiological history given by
      the patient. Routine blood investigations were inconclusive and a chest x-ray was
      normal. The patient was treated by oral doxycycline. The patient responded
      favorably to treatment.

PMID- 19842416
TI  - Scrub typhus in children in a teaching hospital in eastern Taiwan, 2000-2005.
AB  - Scrub typhus is an endemic disease in eastern Taiwan. We conducted a study of
      scrub typhus cases among hospitalized pediatric patients. Twenty-eight pediatric
      cases were confirmed to be scrub typhus (either by immunofluorescence assay or
      polymerase chain reaction) from 2000 to 2005. The medical records of these
      patients were reviewed for demographics and clinical manifestations. The majority
      of the children (60.7%) diagnosed with scrub typhus were male. Approximately half
      the patients were < 5 years old and the mean age (SD) was 6.1 (3.66) years.
      Patients were more likely to live in rural rather than urban areas. The greatest
      number of cases was seen in the spring and summer. The primary clinical symptoms
      included fever (100%), cough (50%), eschar (50%), rash (35.7%), poor appetite
      (42.9%), lymphadenopathy (42.9%), headache (39.3%), and hepatomegaly (35.7%). AC
      reactive protein (CRP) was elevated in 100%, an aspartate aminotransferase (AST)
      was elevated in 100%, an alanine aminotransferase (ALT) level was elevated in
      91.3%, hypoalbuminemia was found in 88.9% and proteinuria in 50%. The mean (SD)
      duration of antibiotics was 11.0 (2.68) days and the mean (SD) duration for fever
      resolution after treatment was 2.8 (2.51) days. Meningoencephalitis was noted in
      6 patients. Our case series had no mortalities. These results suggest that a
      diagnosis of scrub typhus should be suspected in children with fever and
      laboratory evidence of liver dysfunction who live in rural eastern Taiwan.

PMID- 19842417
TI  - Influence of enrichment broths on multiplex PCR detection of total coliform
      bacteria, Escherichia coli and Clostridium perfringens, in spiked water samples.
AB  - Although multiplex PCR amplification condition for simultaneous detection of
      total coliform bacteria, Escherichia coli and Clostridium perfringens in water
      sample has been developed, results with high sensitivity are obtained when
      amplifying purified DNA, but the sensitivity is low when applied to spiked water
      samples. An enrichment broth culture prior PCR analysis increases sensitivity of
      the test but the specific nature of enrichment broth can affect the PCR results.
      Three enrichment broths, lactose broth, reinforced clostridial medium and fluid
      thioglycollate broth, were compared for their influence on sensitivity and on
      time required with multiplex PCR assay. Fluid thioglycollate broth was the most
      effective with shortest enrichment time and lowest detection limit.

PMID- 19842418
TI  - Assessment of different tests to detect methicillin resistant Staphylococcus
      aureus.
AB  - The heterogeneous expression of methicillin resistance in Staphylococcus aureus
      affects the efficiency of tests available to detect it. Not all laboratories have
      access to accurate molecular tests used for this purpose. This study compares the
      performances of four phenotypic tests used to detect methicillin resistant S.
      aureus (MRSA) with the mecA gene polymerase chain reaction. Two hundred thirty
      seven S. aureus isolates were isolated from different patients visiting Sir
      Sundar Lal Hospital, Banaras Hindu University, Varanasi, India and subjected to
      cefoxitin and oxacillin disc diffusion tests, oxacillin minimum inhibitory
      concentration (MIC) test, and oxacillin screen agar test. The tests showed the
      following sensitivities and specificities, respectively: cefoxitin disc diffusion
      (98.5% and 100%), oxacillin disc diffusion (77.3% and 84.6%), oxacillin MIC
      (89.4% and 87.2%), and oxacillin screen agar (87.9% and 94.9%). The cefoxitin
      disc diffusion test can be the best method for routine detection of MRSA when
      molecular techniques are not available. We recommend the Clinical Laboratory
      Standards Institute (CLSI) cut-off point for determining cefoxitin resistance be
      reexamined to see if it should be revised from < or = 19 mm to < or = 20 mm.

PMID- 19842419
TI  - Statistical modelling of childhood diarrhea in northeastern Thailand.
AB  - Diarrhea remains an important cause of morbidity in Thailand, particularly for
      children below age five. This study identified the patterns of diarrhea incidence
      in children below age five in northeastern provinces of Thailand along the border
      with Lao PDR, based on the individual hospital case records of patients with
      diarrhea routinely reported from 1999 to 2004. Linear regression models
      containing the district, season and year as factors were fitted to the log
      transformed disease incidences, with generalized estimating equations used to
      account for spatial correlation between districts. Low disease counts suggesting
      under-reporting were handled by imputation based on these models. This study
      found a seasonal pattern higher in January to March and April to June. Higher
      rates occurred in most districts of Loei and Amnat Chroen Provinces. Using a
      thematic map to display the level of diarrhea incidence by district can provide
      useful information for health authorities to direct their intervention plans more
      effectively and to set up health policies for prevention of disease.

PMID- 19842420
TI  - Effectiveness of school network for childhood obesity prevention (SNOCOP) in
      primary schools of Saraburi Province, Thailand.
AB  - This research was designed to test the effectiveness of a school network for
      childhood obesity prevention (SNOCOP) in primary schools; a program that aimed to
      improve student behavior in terms of knowledge, attitude, intention towards
      obesity prevention, and their food consumption behavior. A quasi-experimental
      pretest-posttest time series study was conducted. By 2-stage stratified sampling
      selection 180 students from 6 schools were assigned to the intervention group and
      195 students from 6 schools to the control group at Saraburi Province, Thailand
      in 2006- 2007. In addition, thirty-one participants being school administrators,
      teachers, parents, and community members from six schools formed the social
      network initiating the intervention. The schoolchildren in the intervention group
      improved their eating behavior, knowledge, attitude, intention towards obesity
      preventive behavior. The six schools of the intervention group changed school
      policies and school activities aiming to reduce the proportion of obesity among
      their student. No such activities could be observed in the control group. These
      findings suggest that the School-Social Network of Childhood Obesity Prevention
      program is an effective means to prevent childhood obesity.

PMID- 19842421
TI  - Laxative anthraquinone contents in fresh and cooked Senna siamea leaves.
AB  - This study determined the contents of total anthraquinone glycosides in Senna
      siamea, which are active laxative form, and total anthraquinones in the fresh
      young leaves, the boiled leaves, and the boiled filtrates by a UV-vis
      spectrophotometric method. Total anthraquinone glycosides and total
      anthraquinones, calculated as rhein, in the fresh young leaves were 0.0523 and
      0.0910% w/w, respectively. The first and second boiled filtrates contained total
      anthraquinone glycosides 0.0334 and 0.0031% fresh weight, respectively. The first
      boiled leaves contained 0.0161% fresh weight and the second boiled leaves
      contained non-detected amount. Total anthraquinones contents in the first and
      second filtrates and the first and second boiled leaves were found to be 0.0721,
      0.0069, 0.0167% fresh weight and non-detected amount, respectively. The results
      showed that the process of preparation of khi lek curry by boiling S. siamea
      young leaves twice with water reduced total anthraquinone glycosides content more
      than 75%. This confirms the traditional use of khi lek curry as a very mild
      laxative drug.

PMID- 19842422
TI  - Investigation of triclosan retention and dental plaque viability with a
      triclosan/PVM/MA copolymer mouthrinse in a Thai population.
AB  - This investigation studied triclosan retention and plaque viability in a group of
      healthy human subjects from Bangkok, Thailand, 12 hours after using a mouthrinse
      containing a triclosan/PVM/MA copolymer system. The results show the retained
      triclosan in the dental plaque was with in or higher than the minimum inhibitory
      concentration (MIC range 0.27-6.25 microg/ml), indicating the triclosan in this
      product remains at an effective concentration in dental plaque. The 12-hour post
      application evaluation demonstrated only 36.5% viability of oral bacteria in
      dental plaque after a one-time use of the mouthrinse. This study shows the
      benefits of using a mouthrinse containing a triclosan/PVM/MA copolymer system for
      providing 12 hours long-lasting anti-bacteria and dental plaque control.

PMID- 19842423
TI  - Loss of L-ascorbic acid in commercial drinking milk caused by milk processing and
      storage times.
AB  - The goals of this study were to determine L-ascorbic acid concentrations in
      various milk products, and to evaluate the effect of storage time on L-ascorbic
      acid in milk. Commercial plain milk samples were obtained from either a raw-food
      market or a supermarket, in Mae Hia, Mueang District, Chiang Mai Province,
      Thailand, during July, 2008. The types of milk were separated based on fat
      percentages (non fat-0%, low fat-1.5%, full fat-3%), and their method of
      processing (pasteurization, UHT). All samples were collected, transported, and
      measured for their L-ascorbic acid concentrations on the same day. The expiration
      date, type of milk, and source of milk were recorded. Pasteurized milk had higher
      L-ascorbic acid levels than UHT milk (p < 0.05), but no differences of L-ascorbic
      acid levels were seen among the milk fat percentage groups. The L-ascorbic acid
      level was significantly positively related to time before the expiration date of
      the milk, indicating that increased storage time of milk is related to decreased
      L-ascorbic acid concentration in the milk. Longer milk storage times resulted in
      lower- L-ascorbic acid levels and pasteurized milk has higher L-ascorbic acid
      levels than UHT milk.

PMID- 19842424
TI  - The patterns and determinants of birth intervals in multiparous women in Babol,
      northern Iran.
AB  - The present study aimed to determine the patterns and factors associated with
      birth intervals in multiparous women in Babol, northern Iran. We conducted a
      cross-sectional study of 500 multiparous women at health centers and referred to
      the hospital for delivery in Babol, northern Iran in 2007. Data were collected
      using a questionnaire, including birth intervals, demographics, fertility
      variables, such as maternal education, maternal age at birth, gender of index
      child, history of still births, child status (infant mortality or still birth) of
      index child, parity, duration of breast feeding, residence area, contraception
      method used, and attendance at a family planning clinic. The data were analyzed
      using a logistic regression model. The mean (+/- SD) birth interval was 61 +/-
      25.7 months. In 3.8% of women the birth interval was < 2 years, in 41.7% it was 4
      5 years and in 28% it was > or = 6 years. The majority of women (76.8%) were age
      20-34 years old at the time of pregnancy. About one-fourth (22.4%) of women were
      > or = 35 years old at the time of pregnancy and 0.8% of women were < 20 years
      old at pregnancy. Maternal age, duration of breast feeding, sex of index child,
      history of still births, history of infant mortality of the index child, type of
      contraception used, regular attendance at a family planning clinics and parity
      showed a significant correlation with birth interval (p < 0.05).

PMID- 19842425
TI  - Feasibility of one-stop antenatal syphilis screening in Ulaanbaatar, Mongolia:
      women and providers perspectives.
AB  - Congenital syphilis can be prevented by antenatal syphilis screening, however,
      the complexity of delivering prenatal service can result in low screening rates,
      and thus lower prevention and treatment rates. One-stop antenatal syphilis
      screening, which includes rapid testing and treatment, is the proposed method to
      overcome this problem. The feasibility of this type of screening needs to be
      tested to dertermine its effectiveness. In this study, the opinions and level of
      satisfaction of women undergoing antenatal care and their health care providers
      regarding a one-stop syphylis screening and treatment service at two antenatal
      clinics in Ulaanbaatar, Mongolia were assessed. The majority of the 246 women
      studied were satisfied with the service. The mean aggregate satisfaction score
      derived from 12 questions regarding specific aspects of satisfaction was 3.2.
      Most providers were also satisfied, not reporting any significant problems
      interfering with routine antenatal care. However, all providers felt the one-stop
      service is time consuming and leads to high staff workloads and needs good
      clinical management. The provider preferred instead to treat husbands
      presumptively to avoid the possibility of diagnosing couples with discordant
      syphilis, which could lead to possible violence. A one-stop syphilis diagnosis
      and treatment service during antenatal care is feasible in Ulaanbaatar, Mongolia
      from both the women's and providers' perspectives.

PMID- 19842426
TI  - Identification of Entamoeba histolytica and Entamoeba dispar by PCR assay of
      fecal specimens obtained from Thai/Myanmar border region.
AB  - Due to the indistinguishable morphology between Entamoeba histolytica
      (pathogenic) and Entamoeba dispar (non pathogenic), PCR-based assays were
      conducted. Based on microscopy, suspected Entamoeba cells were detected in 30 out
      of 455 fecal samples obtained from individuals residing at Thai/Myanmar border
      region. The target genes for PCR amplification included genes encoding small
      subunit rRNA (SSU-rRNA), chitinase and serine rich Entamoeba protein. PCR primers
      derived from SSU-rRNA gene amplified both E. histolytica and E. dispar genes
      producing an amplicon of 1,080 bp, and detected 3 out of 30 samples. PCR primers
      derived from chitinase gene of E. histolytica generating amplicons of 500 and
      1,260 bp, samples were positive in 12 out of 30 samples. Due the large difference
      of gene encoding serine rich protein between E. histolytica and E. dispar, two
      specific sets of primers were designed. SREH-primer set, specific for E.
      histolytica, generated amplicons of 550 and 700 bp and detected 22 out of 30
      samples. SED-primer set, specific to E. dispar, produced an amplicon of 550 bp,
      and together with a nested primer pair generating an amplicon of 477 bp, detected
      16 out of 30 samples. Thus, detection of single and mixed infections of the two
      Entamoeba species could be effectively achieved directly from DNA extracted from
      feces without the need to culture the parasites.

PMID- 19842427
TI  - A survey of ectoparasitic arthropods on domestic animals in Tak Province,
      Thailand.
AB  - In July 2008 a survey of ectoparasites on domestic animals was conducted in the
      Royal Thai Army areas of operation along the Thai-Myanmar Border, Tak Province,
      Thailand. Eleven different ectoparasites were collected: two species of hard
      ticks (Ixodidae), three species of fleas (Siphonaptera) and 6 species of sucking
      or chewing lice (2 species each in the suborders Anoplura, Ischnocera and
      Amblycera) were collected. Domestic dogs (Canis lupusfamiliaris) (n = 94) were
      found infested with 2 species of flea Ctenocephalides felis orientis (86.2%) and
      Echidnophaga gallinacea (1.1%), one species of tick, Rhipicephalus sanguineus
      (21.3%), and one louse species, Heterodoxus spiniger (7.4%). Domestic cats (Felis
      catus) (n = 6) were found infested with only flea species, Ctenocephalides felis
      felis (100%) and E. gallinacea (33.3%). Cattle (Bos indicus) (n = 11) had
      Rhipicephalus (Boophilus) microplus (72.7%), Linognathus vituli (27.3%), and
      Solenopotes capillatus (9.1%) present, while chickens (Gallus domesticus) (n =
      10) had infestations with E. gallinacea (20%), and 3 lice species, Lipeurus
      caponis (10%), Goniodes dissimilis (10%) and Menopon gallinae (60%). This is
      believed to be the first report of S. capillatus collected in Thailand.

PMID- 19842428
TI  - Refractoriness of Aedes aegypti (Linnaeus) to dual infection with dengue and
      chikungunya virus.
AB  - In this study, artificial membrane feeding technique was used to orally feed
      Aedes aegypti with dengue and chikungunya viruses. Virus detection was carried
      out by reverse transcriptase polymerase chain reaction. The study did not detect
      dual infection of Ae. aegypti with dengue and chikungunya virus from the same
      pool or from individual mosquitoes. Oral receptivity of Ae. aegypti to
      chikungunya virus was higher than that of dengue virus.

PMID- 19842429
TI  - Evaluation of PermaNet 2.0 mosquito bednets against mosquitoes, including
      Anopheles minimus s.l., in India.
AB  - Wash resistance and field bioefficacy of PermaNet 2.0 nets, long lasting
      insecticidal nets, against mosquitoes were evaluated in Assam, northeastern
      India. After repeated hand washings at 12-day intervals a decline in the mosquito
      killing ability of PermaNet nets was noted (trend chi2 38.9, p < 0.0001), yet
      these nets retained good insecticidal efficacy for up to 15 wash cycles,
      producing a 72.5% mean mortality of An. minimus 24 hours after a 3-minute
      exposure in World Health Organization cones after 15 washings. Significantly
      fewer (p < 0.001) mosquitoes were captured in self-baited landing collections in
      houses equipped with PermaNet nets than in houses using untreated nets in the
      case of culicines (p < 0.001) but not with anophelines, including An. minimus.
      The use of PermaNet nets resulted in noticeably fewer bites from Culex
      pseudovishnui (68.5%) and Cx. quinquefasciatus (70%). Blood-feeding inhibition of
      mosquitoes in deliberately torn PermaNet nets was seen, indicating a protective
      effect for those sleeping under these nets. No serious adverse effects of the
      PermaNet nets were reported by users.

PMID- 19842430
TI  - Seasonal occurrence of phlebotominae sand flies (Phlebotominae: Diptera) and it's
      correlation with Kala-Azar in eastern Uttar Pradesh, India.
AB  - In this investigation, the species composition of sand flies, and their
      seasonality, nocturnal activity, sex ratio, and resting site, for implementation
      of future control measures, were surveyed in eastern (Gonda and Basti) Uttar
      Pradesh, India. Adult sand flies (2,893) were collected from internal and
      external sites by sticky and light traps. The sand flies were captured using
      light traps hung at different heights in trees and in peridomiciliary and
      extradomiciliary areas of a forest during both dry and rainy months. The traps
      were kept out between sunset and sunrise of the following day. In the
      extradomiciliary environment, the traps were installed at 1, 3 and 5 m above the
      ground. In this investigation, a total of 5 species were obtained: Phlebotomus
      papatasi, P. sergenti, Sergentomyia sintoni, S. punjabensis and S. dentata. The
      number of sand flies peaked in September and declined by December. The maximum
      and minimum numbers were found at 8:00 PM and 5:00 to 6:00 AM, respectively. The
      female to male ratio of the phlebotominae sand flies varied from a high in
      October to a low in June. The number of sand flies in the external regions was
      significantly more (p < 0.05) than the internal regions in all months except May,
      June, December and January. No flagellate infections were observed in any other
      species of sand flies. Using the results of this investigation, health workers in
      this area may be better able to control and prevent leishmaniasis.

PMID- 19842431
TI  - Age-dependent susceptibilities of Bulinus truncatus snails to an aqueous extract
      of Pulicaria crispa (Forssk.) Oliv. (Asteraceae) leaves.
AB  - This study was carried out to investigate the potential use of the herb Pulicaria
      crispa in the biological control of different developmental stages of Bulinus
      truncatus, a major snail intermediate host of urinary schistosomiasis. Age
      dependent susceptibilities of mature adult snails, immature snails, juveniles,
      and one-day old egg masses to aqueous extracts of Pulicaria crispa leaves
      collected from Khartoum (Sudan) and Riyadh (Saudi Arabia) was determined and
      compared. The results show the juvenile snails are the most susceptible, followed
      in descending order by one-day old egg masses, immature snails, and mature adult
      snails. The P. crispa sample collected from Riyadh was significantly more potent
      against B. truncatus than that collected from Khartoum, as indicated by the least
      (LC50) and (LC90) values for all B. truncatus ages.

PMID- 19842432
TI  - Genotypic distribution of hepatitis C virus in voluntary blood donors of northern
      Thailand.
AB  - The purpose of this study was to determine the prevalence and distribution of HCV
      genotypes among voluntary blood donors in northern Thailand. From 1998 to 2000,
      167 serum samples which tested positive for anti-HCV antibodies in the screening
      of voluntary blood donors from 5 provinces in northern Thailand were selected for
      genotyping. Viral RNA was extracted from the sera. The core-E1 region of the HCV
      RNA genome was amplified using a OneStep RT-PCR kit. The core-E1 amplicon was
      sequenced and the HCV genotype was assigned by comparing with the reference
      sequences available in the GenBank database. Of 167 anti-HCV positive serum
      samples, 126 (75.4%) contained HCV RNA as detected by PCR. HCV genotype 3 was the
      most predominant genotype (39.6%), of which 33.3% belonged to genotype 3a and
      6.3% to 3b. Genotype 6 was detected in 31%, and genotype 1 was detected in 27.8%.
      Of the genotype 1 isolates, 14.3% were la, 12.7% were 1b, and 0.8% were 1c. Two
      HCV isolates detected in the present study were untypeable. About 75% of anti-HCV
      positive blood donors had chronic HCV infection. In northern Thailand, genotype
      3a was the most predominant genotype, while genotype 6, 1a and 1b were also
      commonly found. The genotypic distribution of HCV isolates from various regions
      of Thailand were more or less similar. Nevertheless, in this study, the
      prevalence of HCV genotype 6 (31%) was higher than previously reported by others
      (8-18%). Phylogenetic analysis of the HCV isolates detected in the present study
      was also performed.

PMID- 19842433
TI  - Structure and function of HIV-1 CRF01_AE envelope proteins from blood and genital
      fluid isolates.
AB  - The recombinant envelope protein (gp120) of the human immunodeficiency virus type
      1 (HIV-1) CRF01_AE env gene isolated from the corresponding blood (rgp120-F36PC)
      and genital fluid (rgp120-F36VC) specimens obtained from HIV infected individuals
      was successfully produced in both prokaryote and eukaryote cells. The yields of
      HIV-1 recombinant envelope proteins rgp120-F36PC and rgp120-F36VC produced in E.
      coli and in mammalian cells were 1.0 and 1.2, and 0.3 and 0.5 mg/ml,
      respectively. Antibody responses in mice immunized with rgp120-F36VC protein were
      not significantly higher than those with rgp120-F36PC protein. The level of
      antibody response in mice immunized with V3 deleted recombinant gp120 proteins
      from rgp120-F36VC and rgp120-F36PC was not significantly different from wild type
      rgp120 proteins. beta-strands at the tip of the V3 loop of the HIV-1 envelope
      protein were predicted for the wild type genital fluid isolate but not for the
      wild type blood isolate. The replication capacity of both F36PC and F36VC was
      quite efficient. The infectivity assay of the epithelial cell line for pNL4
      3/gp120F36VC was better than for pNL4-3/gp120F36PC. The extra beta-strands in the
      V3 loop may be involved in cell tropism.

PMID- 19842434
TI  - Safety and efficacy of CKBM-A01, a Chinese herbal medicine, among asymptomatic
      HIV patients.
AB  - Complementary remedies represent a potential alternative treatment for chronic
      diseases, including HIV/AIDS cases not meeting criteria for using highly active
      antiretroviral therapy (HAART). This study evaluated the safety and efficacy of
      CKBM-A01, a Chinese herbal medicine, and patient quality of life (QoL).
      Asymptomatic HIV patients with CD4 counts of 250-350 cells/microl were recruited
      into this open-labeled trial. Liquid CKBM-A01 was prescribed for a 36-week
      period. Study participants recorded all symptoms themselves on diary cards. Study
      parameters, including CD4 cell counts, HIV viral loads, and blood chemistry, were
      periodically monitored and questionnaires were used to assess QoL and to help
      with risk reduction. Eighteen volunteers, mean age (+/- SD) 32.07 (+/- 6.88)
      years, had a median (interquartile range, IQR) baseline CD4 count of 292 (268.50
      338.25) cells/microl. No serious drug-related adVerse events due to CKBM-A01 were
      detected during the study. Intermittent diarrhea was reported in 55.6%, weakness
      or skin rash/itching in 50%, and increased bowel movement in 33.7%. No
      significant changes in log viral load or CD4 cell counts were observed at the end
      of the study. Most of the volunteers (72.2%) expressed satisfaction with CKBM-A01
      and had a positive perception. Common colds and nasal symptoms were significantly
      lower during treatment (p = 0.019). CKBM-A01 appeared to be safe but gave no
      significant improvement in QoL in asymptomatic HIV patients, and gave no
      significant improvement in the treatment of HIV based on CD4 cell counts and
      viral loads.

PMID- 19842435
TI  - Phimosis and scrotal lesions in leprosy: two case reports.
AB  - We report two cases of borderline leprosy patients, one with scrotal lesions, the
      other presenting with leprosy on the prepuce with phimosis.

PMID- 19842436
TI  - Diagnostic challenge of gastrointestinal tuberculosis: a report of 34 cases and
      an overview of the literature.
AB  - We report 34 cases of gastrointestinal TB from Malaysia and present an overview
      of the diagnostic challenges. A concerted effort is necessary to improve the
      existing diagnostic methods, and develop and evaluate newer diagnostic tools
      through well designed multi-center studies.

PMID- 19842437
TI  - Streptococcus suis infection: a prospective study in northern Thailand.
AB  - A prospective study of all cases of Streptococcus suis blood or CSF culture
      positive admitted to Lamphun Provincial Hospital in northern Thailand was carried
      out. Fifty-three cases of S. suis were identified, which comprised 70% of all
      viridans streptococci cases. The majority of cases (88.6%) were contracted orally
      and 83.0% had an underlying disease present. Five clinical syndromes were
      identified: acute meningitis (37.2%), septicemia (27.9%), toxic shock syndrome
      (TSS) (23.3%), subacute bacterial endocarditis(SBE) (9.3%) and spondylitis
      (2.3%). The patients with TSS had a lower mean age than those without TSS. S.
      suis IgG and IgM antibody levels in the TSS group were lower than those without
      TSS which is important when considering the clinical syndrome and severity of the
      infection.

PMID- 19842438
TI  - Clinical features of 60 consecutive ICU-treated patients envenomed by Bungarus
      multicinctus.
AB  - In northern Vietnam, Bungarus multicinctus is the only krait of medical
      importance. We report 60 consecutive patients admitted to an ICU in Hanoi during
      2000-2003 because of envenoming by B. multicinctus. Their mean age was 33 years
      (range 12-67), 77% were male. The majority were agricultural workers, 69% of the
      snakebites occurred during the night. The mean length of time until the first
      symptom developed was 3 hours (range 0.5-24 hours). The only sign at the site of
      the bite was fang marks, which were noted in 90%. The most common neuromuscular
      symptoms were ptosis and mydriasis (93%), ophthalmoplegia (82%), jaw weakness
      (90%), pharyngeal pain (83%), palatal palsy (90%), neck muscle paralysis (85%),
      limb paralysis (85%), and paralysis of the respiratory muscles (87%). No
      antivenom was available. Fifty-two patients (87%) needed mechanical ventilation
      for a mean of 8 days. The most surprising laboratory finding was a high rate of
      significant hyponatremia (42%). The mean duration of the ICU stay was 12 days and
      the hospital mortality was 7%. According to the Poisoning Severity Score
      criteria, 54 patients (90%) were classified as severe or lethal envenoming.

PMID- 19842439
TI  - Detection of phenylketonuria by the newborn screening program in Thailand.
AB  - This study evaluated the newborn screening program for phenylketonuria (PKU) in
      Thailand from 1996 to 2006. During the study period, 5,243,841 newborns were
      screened, of which 16 were confirmed to have PKU. The phenylalanine levels ranged
      from 20.30-30.68 mg/dl (mean 25.82 mg/dl). All the patients who were diagnosed
      through the newborn screening program had normal growth and development after
      treatment except for 2 cases who were subsequently found to have a 6
      pyruvoyltetrahydropterin synthase deficiency. Four additional cases of PKU
      diagnosed were siblings of screening detected cases who all presented with mental
      retardation, microcephaly, hypopigmented hair and skin and seizures in one case.
      Although these patients were treated with a phenylalanine restricted diet, all of
      them had moderate to severe psychomotor retardation. The results of this study
      confirm the benefit of early detection and treatment of PKU through the screening
      program.

PMID- 19842440
TI  - Bowel movements of normal Thai infants.
AB  - The aim of this study was to define the bowel movements of healthy Thai infants
      up to 12 months of age. Fifty infants were evaluated at 1, 2, 4, 6, 9 and 12
      months of age. Data regarding bowel habits was recorded by parents daily for 2
      days before coming to the hospital at each visit. The mean frequency of bowel
      movements per day was maximal (3.16 stools) during the newborn period and
      declined (1.59 stools) by the age of 12 months. At birth stool consistency was
      mostly runny, and became consistently more solid by 4 months of age. With
      increasing age, infants produced larger stools: mean volume of stool was 32.7 ml
      at 1 month of age and increased to 45.34 ml at 12 months. Infants started to have
      regular bowel movements at 4 months of age, most of them stopped having bowel
      movements at night by 3 months.

PMID- 19842441
TI  - Assessment of iodine nutrition status among school age children of Nepal by
      urinary iodine assay.
AB  - The present study was undertaken to evaluate the iodine status of Nepalese school
      age children by measuring urinary iodine excretion (UIE). A population based
      cross-sectional study was conducted during November-December 2006 among 1,094
      school age children. Spot urine samples were collected from all children and UIE
      was measured during February to March 2007 by an ammonium persulfate digestion
      microplate (APDM) method. The median UIE at the national level was 193.10
      microg/l, indicating adequate iodine intake in Nepalese schoolchildren. The
      proportion of the population having UIE below 50 microg/l and below 100 microg/l
      were 4.5% and 22.0%, respectively. Determination of precision of the method was
      done following calculation of the inter- and intra-assay coefficient of variation
      (CV). At low, medium and high concentrations of urinary iodine the intra-assay
      CVs were 6.3, 1.8 and 1.9%, respectively. The inter-assay CVs for low, medium and
      high concentrations of urinary iodine were 11.9, 4.9 and 6.2%, respectively.
      Therefore, current iodine nutrition status is at satisfactory levels in Nepal. An
      effective monitoring program must be continued to ensure optimal iodine status
      and prevent the population from developing iodine deficiency disorder (IDD).

PMID- 19842442
TI  - Serum leptin levels and body composition in obese Thai children.
AB  - This study aimed to investigate the relationship between serum leptin
      concentrations and body composition among a sample of obese Thai children. A
      cross-sectional study was conducted in 158 schoolchildren, of whom 107 were obese
      and 51 normal weight; their mean age was 8.2 years. Body weight, height, waist
      circumference (WC), and subcutaneous skinfold thickness at 4 sites (triceps,
      biceps, subscapular, and supra-iliac) were measured. Total body fat (TBF) was
      determined by bioelectrical impedance analysis. Fasting blood samples were
      obtained to determine serum lipid profiles. The food intake of the children was
      estimated from interviews with the children and their mothers to elicit 24-hour
      food recall over 2 days. The results reveal subcutaneous fat skinfold, total body
      fat and waist circumference were significantly higher in obese than normal weight
      children (p < 0.001). Serum leptin levels and lipid profile results, ie serum
      triglycerides (TG), serum total cholesterol (TC), low density lipoprotein
      cholesterol (LDL-C) and energy intake, were also significantly higher in the
      obese children than their normal-weight peers. Stepwise multiple regression
      analysis indicates that among boys, WC (p < 0.001) and serum TG (p = 0.019), and
      among girls, WC (p < 0.001) and TBF (p = 0.030), were significantly associated
      with leptin concentrations. No associations were found between leptin and energy
      intake in these children. A prospective study should investigate the influence of
      leptin levels on weight gain and subcutaneous adiposity, and the
      interrelationship between food intake and circulating leptin levels in children.

PMID- 19842443
TI  - Bacterial meningitis incidence in Thai children estimated by a rapid assessment
      tool (RAT).
AB  - Acute bacterial meningitis is an important cause of morbidity and mortality in
      children. To estimate the incidence of meningitis caused by all types of bacteria
      in Thai children under five years of age, data were collected using a rapid
      assessment tool (RAT) and analyzed. Clinical and laboratory data from suspected
      meningitis cases for a one-year period were retrospectively collected from 5
      selected catchment areas located in the 4 regions of the country. Adjusted
      incidences of confirmed bacterial meningitis were calculated based on laboratory
      quality and lumbar puncture rates. Seventy-five suspected meningitis cases were
      identified among 305,023 children under age five in the catchment areas, with an
      unadjusted incidence of 24.6 per 100,000. Of these, 66.2, 55.9, and 33.8% were
      unconfirmed bacterial, purulent, and confirmed bacterial meningitis cases,
      respectively. Among the confirmed bacterial meningitis cases, 39.1, 26.1, 21.7
      and 13.0% were caused by Haemophilus influenzae type B, gram-positive cocci, gram
      negative bacilli, and Neisseria meningitidis, respectively. After adjusting based
      on the RAT application, the incidence of confirmed bacterial meningitis was about
      double that of the unadjusted incidence. This study gives an interval of possible
      incidences of bacterial meningitis in children under age five, which is between
      the unadjusted (low estimate) and adjusted (high estimate) incidences.

PMID- 19842444
TI  - Factors associated with diagnosis of bacterial pneumonia in children of Northern
      Thailand.
AB  - The purpose of this study was to determine the association between common
      clinical features in general practice, and chest radiographic findings among
      children with suspected bacterial or viral pneumonia. The study was prospective
      hospital-based carried out in Northern Thailand, from 2000 to 2001. One thousand
      three hundred ninety-six children under age five years admitted with suspected
      pneumonia were enrolled in the study. Multinomial logistic regression was used to
      analyze the radiographic results, clinical outcomes, white blood cell (WBC)
      counts, percent poly-morphonuclear cells (% PMN), duration of illness before
      admission, body temperature, age, and gender as variables. Chest radiographs were
      read by a radiologist following the recommendations of the WHO regarding chest
      radiographic reading. Chest radiographic findings were classified as normal,
      viral or bacterial. Fifty-nine children (4.2%) had normal radiographic findings,
      1,233 (88.3%) had a viral appearance on chest radiograph, and 104 (7.5%) had a
      bacterial appearance of chest radiograph. On unadjusted analysis, WBC count, %
      PMN, body temperature, duration of illness before admission, and gender were
      strongly associated with outcomes (p < 0.05). On multivariate analysis, only %
      PMN, duration of illness before admission, and gender were associated with the
      findings of the chest radiograph. A PMN results of 40% to 70% [RRR, 5.64; 95%
      confidence interval (CI), 2.14-14.82], PMN > 70% (RRR, 5.11; 95% CI = 1.71
      15.22), and duration of illness > 4 days (RRR, 5.19; 95% CI = 1.79-15.06) were
      positively associated with bacterial radiographic profile. Female (RRR, 0.50; 95%
      CI = 0.29-0.85) was negatively associated with viral radiographic profile. WBC
      counts in children admitted with suspected pneumonia were not associated with
      chest radiograph findings, but % PMN and duration of illness before admission
      were positively associated with a bacterial radiographic result.

PMID- 19842445
TI  - Rapid flow cytometric test using eosin-5-maleimide for diagnosis of red blood
      cell membrane disorders.
AB  - Conventional diagnosis of hereditary red blood cell (RBC) membrane disorders, in
      particular hereditary spherocytosis (HS), is labor intensive, time consuming and
      requires at least 2 ml of blood, which might be impractical in neonatal period.
      We evaluated the use of eosin-5-maleimide (EMA), a dye that reacts covalently
      with lysine-430 on the first extracellular loop of band 3 protein, for rapid
      screening test of patients with HS and Southeast Asian Ovalocytosis (SAO). Fresh
      RBCs from 142 healthy controls, 50 HS, 17 SAO, 29 hereditary elliptocytosis, 5
      autoimmune hemolytic anemia, 66 patients with beta-thalassemia/HbE, 31 cases with
      alpha-thalassemia (HbH disease) and 4 cases with pyruvate kinase deficiency were
      stained with EMA, and analyzed for their mean channel fluorescence (MCF) using a
      flow cytometer. RBCs from patients with HS and SAO expressed a greater degree of
      reduction in MCF compared to those from normal controls and other hemolytic
      diseases. These findings showed that the fluorescence flow cytometric-based
      method is a simple, sensitive and reliable diagnostic test for RBC membrane
      disorders using a small volume of blood, and results could be obtained within 2
      hours. Such method could serve as a first line screening for the diagnosis of HS
      and SAO in routine hematology before further specific membrane protein
      electrophoresis and molecular diagnosis are employed.

PMID- 19842446
TI  - False positive rates of thalassemia screening in rural clinical setting: 10-year
      experience in Thailand.
AB  - This retrospective study aimed to describe the magnitude of false positive
      screening for thalassemia in a primary care setting of Thailand. The study was
      conducted from 1999 to 2008 and analyzed 13,745 positive cases. It involved a
      combination of one tube osmotic fragility (OF) and dichlorophenol indophenol
      (DCIP) precipitation tests. The number of cases increased over the ten-year
      period, corresponding well to an exponential model. Based on hemoglobin and DNA
      analysis, cases with alpha-thalassemia 1, beta-thalassemia, and hemoglobin E were
      defined as true positive cases, and the remaining were considered as false
      positives. The false positive rate was in the range of 20.1-36.1%. The proportion
      of false positive cases of thalassemia from the screening tests was associated
      with a trend which was statistically significant (p < 0.001). The estimated cost
      of further hemoglobin analysis resulting from false positive cases was
      approximately 40.2-72.2 million THB/year for an estimated 800,000 annual births.
      The combination of the OF and DCIP test, which has been the strategy for
      screening of thalassemia and HbE in pregnant women throughout this country,
      resulted in a large economic burden in terms of high cost and workload associated
      with further hemoglobin and DNA analyses of false positive samples. Measures to
      reduce false positive should be developed and implemented.

PMID- 19842447
TI  - Cardiovascular risk factors in elderly normolipidemic acute myocardial infarct
      patients--a case controlled study from India.
AB  - The goal of the present study was to address the various risk factors associated
      in normolipidemic acute myocardial infarction (AMI) patients admitted to the
      intensive coronary care unit (ICCU). The study compared serum lipid profiles,
      lipid peroxidation markers, antioxidants and inflammatory markers in acute
      myocardial infarction (AMI) patients and age/sex-matched controls. A lipid
      profile, lipid peroxidation, enzyme antioxidants, endogenous antioxidants,
      ischemia modified-albumin (IscMA), ceruloplasmin, C-reactive protein (CRP),
      fibrinogen, lipoprotein (a) and paraoxonase-1 activities were analyzed in 330
      subjects, 165 acute myocardial infarction (AMI) patients and 165 age/sex-matched
      controls. We observed significantly higher (p < 0.0001) total cholesterol and
      triglyceride levels and lower high-density lipoprotein cholesterol (HDL-C) levels
      in the AMI patients. The lipoprotein (a), ceruloplasmin, CRP and fibrinogen
      levels were higher and the bilirubin, ascorbic acid, uric acid, albumin,
      superoxide dismutase, catalase, glutathione peroxidase and paraoxonase-1
      activities were lower in AMI patients than controls. The malondialdehyde (MDA)
      and conjugated diene (CD) levels were significantly higher (p < 0.0001) in AMI
      patients.

PMID- 19842448
TI  - Psychosocial burden of women with abnormal Pap smears.
AB  - This cross-sectional study aimed to describe the psychosocial burden of women
      with abnormal Pap-smear results during the 3 months after recruitment into the
      study. Seventy-five women negative for intraepithelial lesions and 76 women with
      epithelial cell abnormalities were recruited. The two study groups did not differ
      in baseline demographic characteristics or gynecological history. However, the
      mean Health Impact Profile (HIP) scores were higher for the women negative for
      intraepithelial lesions [68.18 +/- 14.22 and 57.74 +/- 16.29, respectively (p <
      0.001)], who were mostly concerned about getting cancer, pain during the visit to
      the gynecologist, and that having sex with their partner may give them an
      infection (p < 0.001). There were no statistically significant differences in
      mean scores for Sheehan Disability Scale (SDS), Work Productivity and Activity
      Impairement Questionnaire (WPAI), Health Utilities Index (HUI), Health State
      Score (HSS), and Hospital Anxiety and Depression (HADS), between the two study
      groups. However, there was a significant difference in mean scores for HSS within
      the younger age group (18-28 years) [(75.00 +/- 13.64, n = 19 and 59.72 +/-
      19.13, n = 18, respectively)] (p = 0.008). The provision of information,
      counseling, and advice, support services and clinician consultation times, need
      strengthening, to help alleviate women's concerns about infection, and their
      worries, anxiety or depression, following an abnormal Pap result.

PMID- 19842449
TI  - Demographic determinants for cesarean delivery in Pattani Hospital.
AB  - We investigated demographic determinants for cesarean delivery based on a
      database of 25,829 singleton births at Pattani Hospital from October 1, 1996 to
      September 30, 2005. This database includes demographic information about the
      mother and delivery type outcomes. Using logistic regression analysis to adjust
      each factor for possible confounding effects of other factors, we found that
      Islamic women were less likely to give birth by cesarean section and older
      mothers were more likely to give birth by cesarean section. There was also an
      association between higher education and cesarian section.

PMID- 19842450
TI  - Prevalence of metabolic syndrome among middle aged women in Babol, Iran.
AB  - Metabolic syndrome is a cluster of interconnected cardiovascular risk factors.
      This research determined the prevalence of metabolic syndrome by body mass index,
      sociodemography, and lifestyle habits of women 30-50 years old in Babol Iran. A
      systematic random sampling was used to select 984 middle aged women from an urban
      area in Babol, Mazandaran, Iran. Screening was used to select eligible women who
      fulfilled selection criteria. The Adult Treatment Panel III (ATP III) criteria
      were used to classify participants as having metabolic syndrome. The overall
      prevalence of metabolic syndrome was 31.0%. Abdominal obesity was observed in
      about 76.6% (n = 273) of subjects. The prevalences of hypertension, high fasting
      blood glucose, high triglycerides and low HDL-cholesterol were 12.1, 12.1, 41.5
      and 48.6%, respectively. Older age (OR = 2.07; CI = 1.56-2.75), higher waist
      circumference (OR = 6.46; 95% CI = 3.48-11.96), higher systolic (OR = 3.84; 95%
      CI = 2.37-6.22) and diastolic blood pressure (OR = 1.89; 95% CI =1.17-3.05), low
      education level (OR = 2.780; CI = 1.80-4.31), housekeeping (OR = 3.92; CI = 1.24
      12.44) and farming occupation (OR = 20.54; 95% CI = 3.54-119.06) were associated
      with increased risk for metabolic syndrome. The odds ratio (OR) showed no
      significant associations between metabolic syndrome and smoking or exposure to
      smoking. This study showed high prevalence of metabolic syndrome in Iranian
      middle aged women. A larger area and population study is needed to enable broader
      recommendations for the prevention of metabolic syndrome.

PMID- 19842451
TI  - Thai Family Health Routines: scale development and psychometric testing.
AB  - The aims of the study were to develop and test the psychometric properties of the
      Thai Family Health Routines (TFHR) scale, a 70-item self-report questionnaire
      used to measure the health of Thai families through their routine behaviors in
      daily life. Development of the TFHR was based on the structural domains of
      Denham's Family Health Model. The TFHR scale was initially composed of 85 items
      and tested on 1,040 families living in the central region of Thailand. The
      confirmatory factor analysis, with an acceptable factor structure model, yielded
      70 items aligned with six factors: self-care, safety and prevention, mental
      health behavior, family care, family caregiving, and illness care routines. The
      preliminary psychometric properties demonstrated that the TFHR scale had
      satisfactory internal consistency, criterion validity, and construct validity.
      The test results suggested that the TFHR scale has potential benefits for family
      and community nurses to assess Thai family health for both research and clinical
      purposes.

PMID- 19842452
TI  - Leisure-time walking and compliance with ACSM/AHA aerobic-related physical
      activity recommendations: 1999-2004 NHANES.
AB  - BACKGROUND: Adults integrate walking into their leisure-time (LT) in a variety of
      ways, including the use of walking as their only outlet for leisure-time physical
      activity (LTPA). The purpose of this study was to examine how LT walking relates
      to compliance with the 2007 ACSM/AHA guidelines for aerobic-related physical
      activity (PA). METHODS: The study sample (N = 14,470 adults, 20+ years of age)
      came from the 1999 to 2004 NHANES. PA Interviews (past month) allowed each LT
      active subject to be classified by walking behavior (LTPA Active-No Walking,
      Walking-Only, Walking-Plus other LTPA). Walking prevalence, frequency (bouts per
      week), duration (minutes per bout), and compliance with ACSM/AHA recommendations
      were examined in SUDAAN. RESULTS: Overall, 34.4% of adults in the U.S. walk in
      their LT. Among these active LT walkers, 34.8% were Walking-Only and 65.2% were
      Walking-Plus adults. Related to compliance with PA recommendations, Walking-Only
      (29.4%; 95% CI = 26.3 to 32.5) adults were significantly less likely than Walking
      Plus (74.6%; 95% CI = 72.6 to 76.7) adults to be compliant with guidelines. The
      frequency of LTPA explains this difference in compliance (3.4 vs. 7.6 bouts/week,
      respectively). CONCLUSIONS: Walking-Only adults should be targeted for increased
      compliance with PA recommendations by promoting walking frequency and added
      variety among LTPAs.

PMID- 19842453
TI  - Recommended levels of physical activity and health-related quality of life among
      overweight and obese adults in the United States, 2005.
AB  - BACKGROUND: Since overweight (25 < or = BMI < 30) and obesity (BMI > or = 30
      Kg/m2) are associated with poor health-related quality of life (HRQOL) and
      regular physical activity is associated with higher levels of HRQOL, the authors
      examined the relationship between physical activity and HRQOL among overweight
      and obese adults (age > or = 18 years) residing in the United States. METHODS:
      Using the 2005 BRFSS survey, they examined the independent relationship between
      recommended physical activity and measures of HRQOL developed by the Centers for
      Disease Control and Prevention among 283,562 adults age 18 years or older with
      overweight or obesity. Measures of physical activity, height, weight, and HRQOL
      were self-reported. Multivariable logistic regression was used to obtain odds
      ratios and 95% confidence intervals adjusted for age, race/ethnicity, sex,
      education, smoking status, chronic disease, and body-mass index. RESULTS: The
      proportion of adults with overweight and obesity who attained recommended levels
      of physical activity had higher levels of HRQOL than physically inactive adults
      for all age, racial/ethnic, and sex groups. After multivariable adjustment,
      overweight and obese adults who met the recommended level of physical activity
      had higher levels of HRQOL than physically inactive adults across all age strata.
      CONCLUSIONS: These results highlight the HRQOL role that physical activity can
      have among overweight and obese persons despite their excess body weight.

PMID- 19842454
TI  - Dog ownership and health-related physical activity among Japanese adults.
AB  - BACKGROUND: Dog ownership appears to have associated health benefits as a result
      of increased physical activity through dog walking. This study examined the
      association between dog ownership and health-related physical activity among
      Japanese adults. METHODS: Male and female respondents to an Internet-based cross
      sectional survey were divided into the following groups: dog owner (DOG), nondog
      pet owner (NDOG), and nonpet owner (NPOG). Moderate and vigorous physical
      activity amount (MVPA), walking amount (Walking), and sedentary behavior time
      (SB) were estimated from the International Physical Activity Questionnaire.
      Analyses of covariance and logistic regression analysis were used. RESULTS: The
      differences in MVPA, Walking, and SB were statistically significant among the
      three groups. DOG had a significantly greater amount of MVPA than NDOG and NPOG.
      DOG also had a significantly greater amount of Walking and less SB time than
      NPOG, and DOG was 1.5 times more likely to meet the physical activity
      recommendation than NDOG and NPOG. CONCLUSIONS: The dog owners had higher
      physical activity levels than owners of other kinds of pets and those without any
      pets, suggesting that dogs may play a major role in promoting physical activity.
      However, only 30% of the dog owners met the recommended criteria for physical
      activity.

PMID- 19842455
TI  - Objectively measured age-related changes in the intensity distribution of daily
      physical activity in adults.
AB  - BACKGROUND: The purpose of the present investigation was to examine the
      relationship between age and the intensity of the daily physical activity in men
      and women, aged 18 to 69 years. METHODS: A total 507 volunteers continuously wore
      a pedometer with a uni-axial accelerometer (Lifecorder, Kenz, Japan) for 7 days,
      to determine the number of steps (steps/ day) as well as the time spent in
      physical activity (minutes/day) at light (below 3 METs), moderate (3 to 6 METs),
      and vigorous (above 6 METs) intensities, respectively. All procedures carried out
      in the present investigation were conducted from 1999 to 2000 in Japan. RESULTS:
      The time spent in moderate to vigorous intensity physical activity significantly
      decreased with aging (P < 0.01). In contrast, the middle- to older-aged
      individuals spent a longer time in light intensity physical activity in
      comparison with the younger individuals (P < 0.05). Furthermore, these age
      associated differences of physical activity were also significant, even though
      the number of steps did not differ significantly. CONCLUSIONS: These results
      indicate that the intensity of daily physical activity decreases with increasing
      age regardless of the amount of daily physical activity.

PMID- 19842456
TI  - Reasons for urban trail use predict levels of trail-related physical activity.
AB  - BACKGROUND: Efforts to increase community levels of physical activity through the
      development of multiuse urban trails could be strengthened by information about
      factors predicting trail use. This study examined whether reasons for trail use
      predict levels of physical activity on urban trails. METHODS: Adults (N = 335)
      living within a 1-mile buffer zone of urban trails in Chicago, Dallas, and Los
      Angeles completed a self-report measure assessing demographics, reason for trail
      use, and physical activity on the trail. Accelerometers measured total daily
      moderate-to-vigorous physical activity (MVPA). Environmental features of the
      urban trail were assessed with the Systematic Pedestrian and Cyclist
      Environmental Scan for trails measure. Multivariate regression analyses were
      conducted that accounted for clustering of individuals within trail segments.
      RESULTS: After controlling for demographic and environmental factors and total
      daily MVPA, reasons for trail use significantly predicted recreational but not
      transportation activity. Recreational trail activity was greater for participants
      who reported exercise and health reasons for trail use as compared with other
      reasons (ie, social interaction, enjoying nature, walking pets) for recreational
      trail use. CONCLUSIONS: To increase the use of urban trails, it may be useful to
      promote the health and exercise benefits of recreational trail use.

PMID- 19842457
TI  - Healthy Campus 2010: physical activity trends and the role information provision.
AB  - BACKGROUND: The primary purpose of this investigation was to examine the
      frequency and type of self-reported physical activity behavior in postsecondary
      students with reference to Healthy Campus 2010 objectives. The secondary purpose
      was to explore the role of information provision in terms of promoting physical
      activity behavior in postsecondary students. METHODS: Postsecondary students were
      assessed (N = 127360). Employing a trend survey design, the frequency and type of
      physical activity behavior was assessed along with physical activity/fitness
      information provision across a five year period between 2000 to 2004. RESULTS: In
      2004, respondents meeting Healthy Campus 2010 objectives for self-reported
      moderate and vigorous physical activity (MVPA) was 42.20% (95% CI = 41.75 to
      42.65) and 48.60% (95% CI = 48.14 to 49.06) for strength (STRENGTH) training
      behavior. Progress quotients demonstrated that 12.93% and 7.87% of target
      objective for MVPA and STRENGTH respectively had been achieved from baseline.
      Those who received information reported engaging in more frequent physical
      activity behavior compared with those who did not (P < .001). CONCLUSIONS:
      Results suggest the need for continued commitment to increasing physical activity
      behavior. The provision of physical activity/fitness information may be one
      mechanism through which this can be achieved.

PMID- 19842459
TI  - Effectiveness of the First step Program delivered by professionals versus peers.
AB  - BACKGROUND: To compare the effectiveness of a theory-based lifestyle physical
      activity (PA) program delivered to individuals with type 2 diabetes in diabetes
      education centers by professionals and peers. METHODS: Changes over 16 weeks in
      PA (steps/day) and related variables (weight, waist girth, resting heart rate,
      systolic and diastolic blood pressures) were compared (RMANOVA) for two groups:
      157 participants led by 13 different professionals versus 63 participants led by
      5 peer leaders. RESULTS: Overall, the 81 male and 139 female participants (age =
      55.7 +/- 7.3 years, BMI = 35.2 +/- 6.6) showed an incremental change of 4,059 +/-
      3,563 steps/day, which translates into an extra 37 minutes of daily walking (P <
      .001). Statistically significant improvements were also seen in weight, waist
      girth, and blood pressure (all P < .001) and resting heart rate (P < .05). There
      were no significant differences in outcomes between professional and peer-led
      groups. CONCLUSIONS: A theory-based behavior modification program featuring
      simple feedback and monitoring tools, and with a proven element of flexibility in
      delivery, can be effective under real-world conditions while addressing
      inevitable concerns about resource allocation. Program delivery by peer leaders,
      in particular, could address a potential obstacle to dissemination by helping to
      alleviate existing high caseload demands on diabetes educators.

PMID- 19842460
TI  - Predictors of response to an intervention modifying physical activity and
      sedentary behavior in overweight/obese children: attitudes vs. behavior.
AB  - OBJECTIVE: To compare liking and other attitudes toward physical activity (PA)
      and television (TV) viewing versus PA behavior and time viewing TV at baseline as
      predictors of response to lifestyle intervention in 30, 8 to 12 year old
      overweight/obese children. METHOD: Secondary analyses from a randomized
      controlled trial designed to increase PA and reduce sedentary behavior. PA was
      measured by accelerometers worn by participants every day for 8 weeks. TV viewing
      at baseline and during intervention was assessed by self-report. RESULTS:
      Multiple regression analyses showed that base rates of PA and TV viewing
      significantly predicted changes in PA (Beta = .39, P < .05) and TV viewing (Beta
      = .37, P < .05) during the intervention, even after statistically controlling for
      child age, gender, body mass index, as well as baseline attitudes and liking of
      PA and TV viewing. However, self-reported liking of TV viewing and PA, perceived
      adequacy, and predilection were not predictive of response to intervention.
      CONCLUSIONS: Baseline measure of PA and TV viewing behaviors may be better
      predictors of response to lifestyle intervention than measure of liking and other
      attitudinal variables of PA. The theoretical and clinical implications of these
      findings are discussed.

PMID- 19842458
TI  - Eight-month follow-up of physical activity and central adiposity: results from an
      Internet-delivered randomized control trial intervention.
AB  - BACKGROUND: Less than half of U.S. adults engage in the recommended amount of
      physical activity (PA). Internet-delivered PA programs increase short-term PA but
      long-term adherence is largely equivocal. PURPOSE: To determine whether increased
      PA following the 16-week Internet-delivered Active Living Every Day (ALED-I)
      program is maintained 8 months later in sedentary and overweight rural adults.
      METHODS: In our previous randomized controlled trial (N = 32; 18 intent-to-treat
      controls, 14 ALED-I interventions), the ALED-I group increased PA (+1384
      steps/day; E.S. = 0.95) and reduced central adiposity. Nine original intervention
      participants and ten delayed intent-to-treat control participants completed ALED
      I and an 8-month followup. Pedometer-measured PA, anthropometric variables, and
      cardiometabolic disease risk factors were assessed at baseline, postintervention,
      and at 8 months. RESULTS: Control crossover participants increased PA (+1337
      steps/ day; P = .04). Eight months following completion of ALED-I (N = 19), PA
      levels relapsed (-1340 steps/day) and were similar to levels before the
      intervention (6850 +/- 471 steps/day vs. 6755 +/- 543 steps/day; P = .89). Total
      cholesterol and triglycerides improved, -9.9% and -18.2%, respectively, and
      reductions in central adiposity were maintained (97.1 +/- 2.2 cm vs. 97.2 +/- 2.2
      cm; P = .66). CONCLUSIONS: The ALED-I intervention was efficacious in the short
      term but did not produce longer-term adherence to PA. Future theory-based
      internet-delivered interventions that produce habituation of increased PA are
      warranted.

PMID- 19842461
TI  - Efficacy of an accelerometer-guided physical activity intervention in community
      dwelling older women.
AB  - BACKGROUND: Although many Japanese older adults spend more than an hour each day
      walking for exercise, the intensity is often lower than the minimum level
      associated with various health benefits. The purpose of this study was to
      evaluate the efficacy of a lifestyle physical activity intervention on improving
      quantity and quality of daily physical activity (DPA) as well as
      cardiorespiratory endurance in community-dwelling older women. METHODS: 68 women
      (60-78 yr of age) were randomly assigned to either a lifestyle physical activity
      intervention group (LIFE) or control group. During the 12-wk intervention,
      feedback based on accelerometer DPA data (number of daily steps (STEPS) and time
      spent performing daily moderate intensity physical activity (MPA) was provided to
      each participant in LIFE every two weeks. Cardiorespiratory endurance was
      evaluated using the 12-Minute Walk Test (12-MW). RESULTS: Following the 12-wk
      intervention, significant group interactions were observed for STEPS, MPA, and
      cardiorespiratory endurance. LIFE increased STEPS by 16%, MPA by 53%, and the
      distance walked during the 12-MW by 10%. CONCLUSIONS: Promotion of DPA using
      accelerometers can significantly improve quantity and quality of daily physical
      activity as well as cardiorespiratory endurance in older women.

PMID- 19842462
TI  - Compliance and acceptability of maintaining a 6-month pedometer diary in a rural,
      African American community-based walking intervention.
AB  - BACKGROUND: Limited research has been done on the compliance and acceptability of
      maintaining pedometer diaries for an extensive time frame in community-based
      interventions targeting minority populations. METHODS: Community "coaches" led
      participants in a 6-month community-based walking intervention that included
      wearing pedometers and maintaining pedometer diaries for the study duration.
      Descriptive statistics and ANOVA tests were used to evaluate compliance rates for
      maintaining diaries and daily step counts. After the intervention, focus groups
      were used to explore opinions regarding pedometers. Audiotapes were transcribed
      and evaluated using systematic content analysis. RESULTS: The 8 coaches and 75
      enrolled walking participants were primarily African American (98%) women (94%).
      Overall, the group (N = 83) submitted 85% of all possible pedometer diaries and
      recorded 73% of all possible daily step counts. Walking-group members were
      significantly (P < .01) more compliant if their coach was also compliant.
      Identified benefits of wearing pedometers and maintaining diaries outnumbered the
      barriers. Participants were enthusiastic about wearing the pedometers and
      indicated that the weekly diaries provided a source of motivation. CONCLUSIONS:
      This research suggests pedometer diaries are a viable intervention tool and
      research method for community-based physical activity interventions targeting
      African Americans and highlights the need for social support to promote pedometer
      diary compliance.

PMID- 19842463
TI  - Self-reported adherence: a method for evaluating prescribed physical activity in
      primary health care patients.
AB  - BACKGROUND: Physical activity on prescription, as a method for increasing
      physical activity, has attracted attention in recent years. However, few studies
      have examined adherence as a primary outcome variable. The aim of this article
      was to examine self-reported adherence to individualized prescribed physical
      activity in a routine primary health care setting. METHODS: Patients receiving an
      individualized physical activity on prescription (FaR) for prevention or
      treatment of disease were recruited from 13 Swedish primary health care units.
      Self-reported adherence, physical activity level, readiness to change to a more
      physically active lifestyle, and well-being were measured with questions at
      baseline and after 6 months in 240 patients (mean age 51, range 12 to 80, 75%
      women). RESULTS: At the 6-month follow-up a majority (65%) of the patients
      reported adherence to the prescription. Partial adherence was reported by 19% and
      nonadherence by 16%. There was a relationship between adherence and well-being
      and stages of action or maintenance. CONCLUSIONS: The results demonstrate that
      adherence to physical activity on prescription is as good as adherence to other
      treatments for chronic diseases. This is significant because even a small
      increase in physical activity is important both on an individual level and for
      public health.

PMID- 19842464
TI  - Associations of leisure-time physical activity with balance and lower extremity
      strength: a validation of the neuromuscular part of the Physical Activity Pie.
AB  - BACKGROUND: The importance of neuromuscular-type exercise (NME) has been
      recognized in recent recommendations for public health. However, the knowledge on
      associations and dose response of different types of leisure-time physical
      activity (LTPA) with musculoskeletal fitness and health is incomplete. This study
      evaluated the validity of the NME recommendation for public health introduced by
      the Physical Activity Pie. METHODS: Engagement in LTPA and health-related fitness
      were assessed in 2 consecutive studies with the same adult population age 30 to
      69 years (n = 575). Cross-sectional associations between different LTPA types and
      motor and musculoskeletal fitness were examined by logistic-regression models.
      RESULTS: Engagement in NME was associated with good static and dynamic balance
      and lower extremity strength. The highest odds ratios (OR) were found between
      brisk NME and static balance (most vs least fit OR = 2.39, moderate vs least fit
      OR = 1.94) and brisk NME and leg strength (more vs least fit OR = 2.10). Some
      associations were also found between brisk aerobic exercise and good balance.
      CONCLUSIONS: This cross-sectional study suggests that the recommendation for NME
      in the Physical Activity Pie is valid in terms of balance and leg strength, the 2
      major fitness factors related to mobility functioning, especially among aging
      adults.

PMID- 19842465
TI  - Association between physical activity in parks and perceived environment: a study
      with adolescents.
AB  - BACKGROUND: The purpose of this study was to analyze the relationship between
      adolescents' physical activity practice and their perception about the
      environment of urban parks. METHODS: A school-based representative sample (n =
      1,718; boys = 40.4%) of teenagers of Curitiba, Southern region of Brazil. A
      questionnaire was employed to identify perceived parks environmental features as
      well as physical activity practice in the parks (PAP), habitual physical activity
      (HPA) and demographics. The relationship between PAP and parks environments was
      analyzed through multivariate logistic regression controlling for age and
      socioeconomic status, HPA and parks distance. RESULTS: After controlling for
      confounders PAP was associated with lack of space to be physically active,
      activities to choose from and equipments for both boys and girls, (odds ratio
      (OR)-ranging from 1.5 to 1.8). Among boys, having people of same age (OR = 1.5)
      and accessibility (OR = 2.0) showed association with PAP only in crude analysis.
      However, among girls, to be bulled or teased (OR = 1.4) and accessibility (OR =
      1.7) were associated with PAP after confounding control. CONCLUSIONS: The results
      showed that specific attributes in parks may be considered and offered to
      increase the likelihood of physical activity practice among adolescents in such
      locations.

PMID- 19842466
TI  - How school time physical activity is the "big one" for daily activity among
      schoolchildren: a semi-experimental approach.
AB  - BACKGROUND: This study was designed to model the relationship between an
      ActiGraph-based "in-school" physical activity (PA) and the daily one among
      children and to quantify how school can contribute to the daily PA
      recommendations. METHOD: Fifty boys and 43 girls (aged 8 to 11 years) wore
      ActiGraph for 2 schooldays of no structured PA. The daily moderate-to-vigorous PA
      (MVPA(d)) was regressed on the school time MVPA (MVPA(s)). Then, a ROC analysis
      was computed to define the required MVPA(s). RESULTS: Children spent 57% of their
      awaking time at school. School time PA opportunities (ie, recesses: approximately
      18% of a child's awaking time) accounted for > 70% of the MVPA(d) among children.
      Then, MVPA(d) (Y) could be predicted from MVPA(s) (X) using the equation: Y= 2.06
      X0.88; R2 = .889, P < .0001. Although, this model was sex-specifically
      determined, cross-validations showed valid estimates of MVPA(d). Finally, with a
      sensitivity of 100% and a specificity of 90%, MVPA(s), a 34 min x d(-1) was
      required to prompt the daily recommendation. CONCLUSIONS: The current study shows
      the contribution of MVPA at school to recommended activity levels and suggests
      the value of activity performed during recesses. It also calls for encouraging
      both home- and community-based interventions, predominantly directed toward
      girls.

PMID- 19842467
TI  - The International Universities Walking Project: development of a framework for
      workplace intervention using the Delphi technique.
AB  - BACKGROUND: This paper aimed to use the Delphi technique to develop a consensus
      framework for a multinational, workplace walking intervention. METHODS: Ideas
      were gathered and ranked from eight recognized and emerging experts in the fields
      of physical activity and health, from universities in Australia, Canada, England,
      The Netherlands, Northern Ireland, and Spain. Members of the panel were asked to
      consider the key characteristics of a successful campus walking intervention.
      Consensus was reached by an inductive, content analytic approach, conducted
      through an anonymous, three-round, e-mail process. RESULTS: The resulting
      framework consisted of three interlinking themes defined as "design,
      implementation, and evaluation." Top-ranked subitems in these themes included the
      need to generate research capacity (design), to respond to group needs through
      different walking approaches (implementation), and to undertake physical activity
      assessment (evaluation). Themes were set within an underpinning domain, referred
      to as the "institution" and sites are currently engaging with subitems in this
      domain, to provide sustainable interventions that reflect the practicalities of
      local contexts and needs. CONCLUSIONS: Findings provide a unique framework for
      designing, implementing, and evaluating walking projects in universities and
      highlight the value of adopting the Delphi technique for planning international,
      multisite health initiatives.

PMID- 19842468
TI  - Shedding light on water structure at air-aqueous interfaces: ions, lipids, and
      hydration.
AB  - An account is given of the current state of understanding of aqueous salt, acid,
      and lipid/water surfaces, interfacial depth, and molecular organization within
      the air-solution interfacial region. Water structure, hydration, surface
      propensity of solutes, and surface organization are discussed. In this
      perspective, vibrational sum frequency generation spectroscopic studies of
      aqueous surfaces are interpreted. Comment on future directions within the field
      of aqueous surface structure is provided.

PMID- 19842469
TI  - Local condensation around oxygen vacancies in t-LaNbO4 from first principles
      calculations.
AB  - First principles calculations reveal that formation of a fully ionized oxide
      vacancy leads to local condensation of coordination polyhedra forming Nb3O11(7-)
      in t-LaNbO4.

PMID- 19842470
TI  - The exploration of domain sizes and orientation directions in ordered assembled
      nanoparticles with electron Moire fringes.
AB  - Structural information such as domain sizes and orientation directions in ordered
      assembled nanoparticles can be simultaneously obtained by using generated
      electron Moire fringes, without direct observation of the nanoparticles.

PMID- 19842471
TI  - Incorrect diatomic dissociation in variational reduced density matrix theory
      arises from the flawed description of fractionally charged atoms.
AB  - The behaviour of diatomic molecules is examined using the variational second
      order density matrix method under the P, Q and G conditions. It is found that the
      method describes the dissociation limit incorrectly, with fractional charges on
      the well-separated atoms. This can be traced back to the behaviour of the energy
      versus the number of electrons for the isolated atoms. It is shown that the
      energies for fractional charges are much too low.

PMID- 19842472
TI  - Coping with the anisotropy in the analytical representation of an ab initio
      potential energy surface for the Cl2 dimer.
AB  - The intermolecular potential energy surface (PES) of the Cl2 dimer is calculated
      at the MP2/aTZ + b level of ab initio theory. A quantitative measure is proposed
      for comparison of the anisotropy of PESs of different systems at different
      intermolecular distances. A high degree of anisotropy at short and intermediate
      distances results in the failure of fitting strategies that are based on the
      angular expansion of the potential energy. To tackle this problem, a step-by-step
      fitting strategy is designed for analytical representation of the PES. The global
      minimum energy configuration of the dimer is found to be a distorted L-shape
      structure with a well depth of around 615 cm(-1). The PES is finally scaled to
      minimize deviations between calculated and experimental second virial
      coefficients.

PMID- 19842473
TI  - Band gap effect on the photocatalytic activity of supramolecular structures
      obtained by entrapping photosensitizers in different inorganic supports.
AB  - Different metallophthalocyanines and 2,4,6-triphenylpyrylium (TP+) ions were
      entrapped in different inorganic supports such as Y zeolite, mesoporous MCM-41,
      TiO2-SiO2 and SiO2 following a specific protocol. The resulting supramolecular
      structures were characterized by chemical analysis and diffuse reflectance UV-vis
      measurements. The determination of the band gap on the basis of UV-vis
      measurements showed that the host is not a spectator in this process and an
      electronic interaction occurs that lowers the band gap of the support. The XPS
      measurements were performed with an in situ X-ray photoelectron spectrometer,
      which can be operated at pressures of up to 1 mbar at the sample. They indicated
      that the formation of the supramolecular structure generates a stable
      environment, in which the oxidation state of the metal can still be influenced by
      reaction of the metal center with gas molecules. The photocatalytic tests carried
      out in photodecomposition of dipropyl sulfide showed a good correlation between
      the band gap values and the photocatalytic activity for metallophthalocyanine
      complexes. It is remarkable that the triphenylpyrylium ion follows the same trend
      observed for metallophthalocyanines, although it is a different type of
      photosensitizer.

PMID- 19842474
TI  - Reduction of protons assisted by a hexanuclear nickel thiolate metallacrown:
      protonation and electrocatalytic dihydrogen evolution.
AB  - The hexanuclear metallacrown [Ni6L12] (L is mu-S-CH2-CH2-S-C6H4-Cl) has been
      demonstrated to functionally resemble the [NiFe] hydrogenases. Protonation of the
      [Ni6L12] cluster was studied employing 1H NMR spectroscopy by the sequential
      additions of dichloroacetic acid or p-toluenesulfonic acid monohydrate into
      solutions of [Ni6L12] in CD2Cl2 and DMF-d7, respectively; protonation takes place
      on the thioether sulfurs available in the metallacrown. Electrochemical
      properties of both the parent and protonated [Ni6L12] species have been studied
      using cyclic voltammetry. Protonated [Ni6L12] shows an interesting
      electrocatalytic property as it catalyzes the reduction of protons to molecular
      hydrogen in the presence of protic acids, such as dichloroacetic acid and
      chloroacetic acid at -1.5 and -1.6 V vs. Ag/AgCl in DMF, respectively. A
      catalytic cycle has been proposed based on the observations from the NMR
      spectroscopic and electrochemical studies of the metallacrown. The behavior of
      this electrocatalyst was further studied by its immobilization on the surface of
      a pyrolytic graphite electrode; reduction of a dichloroacetic acid solution in
      acetonitrile on the surface of the modified electrode occurs at 220 mV more
      positive potential compared to the unmodified electrode.

PMID- 19842475
TI  - Molecular dynamics simulation of the electrochemical interface between a graphite
      surface and the ionic liquid [BMIM][PF6].
AB  - The structure of the electrical double layer in the ionic liquid 1-butyl-3
      methylimidazolium hexafluorophosphate ([BMIM][PF6]) near a basal plane of
      graphite was investigated by molecular dynamics simulation. The calculations were
      performed both for an uncharged graphite surface and for positively and
      negatively charged ones. It is found that near an uncharged surface the ionic
      liquid structure differs from its bulk structure and represents a well-ordered
      region, extending over approximately 20 A from the surface. Three dense layers of
      ca 5 A thick are clearly observed at the interface, composed of negative ions and
      positively charged rings. It is established that in the first adsorption layer
      the imidazolium ring in the [BMIM]+ cation tends to be arranged in parallel to
      the graphite surface at a distance of 3.5 A. The [PF6]- anion is oriented in such
      a way that the phosphorus atom is at a distance of 4.1 A from the surface and
      triplets of fluorine atoms form two planes parallel to the graphite surface. Ions
      adsorbed at the uncharged surface are arranged in a highly defective 2D hexagonal
      lattice and the corresponding lattice spacing is approximately four times larger
      than that of the graphene substrate. The influence of the electrode potential on
      the distribution of electrolyte ions and their orientation has also been
      investigated. Increase in the electrode potential induces broadening of the angle
      distribution of adsorbed rings and a shift of the most probable tilt angle
      towards bigger values. It was shown that there are no adsorbed anions on the
      negatively charged surface (sigma = -8.2 microC cm(-2)), but the surface
      concentration of adsorbed cations on the positively charged surface (sigma = +8.2
      microC cm(-2)) has a nonzero value. In addition, the influence of the surface
      charge (+/- sigma) on the volume charge density and electric potential profiles
      in an electrolyte was studied. The differences in the cation and anion structure
      result in the fact that the integral capacitance of the electrical double layer
      depends on the electrode polarity and equals C = 4.6 microF cm(-2) at sigma = 
      8.2 microC cm(-2) and C = 3.7 microF cm(-2) at sigma = +8.2 microC cm(-2).

PMID- 19842476
TI  - Motion of single wandering diblock-macromolecules directed by a PTFE nano-fence:
      real time SFM observations.
AB  - Using SFM we have observed a peculiar twisting motion of diblock macromolecules
      pre-collapsed in ethanol vapour during their subsequent spreading in water
      vapour. The intrinsic asymmetry of the diblock macromolecules has been considered
      to be the reason for such twisting. Further, friction-deposited PTFE nano-stripes
      have been employed as nano-trails with the purpose of inducing lateral directed
      motion of the asymmetric diblock macromolecules under cyclic impact from the
      changing vapour surroundings. Indeed, some of the macromolecules have
      demonstrated a certain tendency to orient along the PTFE stripes, and some of the
      oriented ones have moved occasionally in a directed manner along the trail.
      However, it has been difficult to reliably record such directed motion at the
      single molecule level due to some mobility of the PTFE nano-trails themselves in
      the changing vapour environment. In vapours, the PTFE stripes have demonstrated a
      distinct tendency towards conjunction. This tendency has manifested itself in
      efficient expelling of groups of the mobile brush-like molecules from the areas
      between two PTFE stripes joining in a zip-fastener manner. This different kind of
      vapour-induced cooperative macromolecular motion has been reliably observed as
      being directed. The PTFE nano-frame experiences some deformation when
      constraining the spreading macromolecules. We have estimated the possible force
      causing such deformation of the PTFE fence. The force has been found to be a few
      pN as calculated by a partial contribution from every single molecule of the
      constrained group.

PMID- 19842477
TI  - A spectroscopic and DFT study of thiophene-substituted metalloporphyrins as dye
      sensitized solar cell dyes.
AB  - A combination of density functional theory calculations, electronic absorption
      and resonance Raman spectroscopy has been applied to a series of beta-substituted
      zinc porphyrins to elucidate how the substituent affects the electronic structure
      of the metalloporphyrin and assign the nature of electronic transitions in the
      visible region. The use of conjugated beta substituents invokes a large
      perturbation to both the nature and energy of the frontier molecular orbitals and
      results in the generation of additional molecular orbitals from the parent
      metalloporphyrin species. A complicated electronic absorption spectra is observed
      which can be rationalised by an extension of Goutermans' four-orbital model. The
      excitations involved in the visible transitions have been determined using
      resonance Raman spectroscopy. This has revealed that the B band retains much of
      its original nature and is centred largely on the porphyrin core. Additional
      electronic transitions invoke population of orbitals localised on the substituent
      chain. The nature of the electronic transitions depends heavily on the type of
      beta substituent. The results of this investigation question some previously held
      beliefs for the rational design of metalloporphyrins for dye-sensitized solar
      cell applications.

PMID- 19842478
TI  - Thermal reversion of spirooxazine in ionic liquids containing the [NTf2]- anion.
AB  - We have investigated the kinetic and thermodynamic parameters of thermal
      reversion of the spirooxazine 1,3,3-trimethyl-5'-(2-benzothiazolyl)-spiroindoline
      2,3'-naphtho(2,1-b)(1,4) oxazine (SO) in molecular solvents and ionic liquids
      containing the [NTf2]- anion. E(T)30 and Kamlet-Taft parameter studies were
      employed to interpret IL polarity and attempt to rationalise the kinetic-polarity
      relationship of MC --> SO relaxation. The observed thermal relaxation of SO
      within ionic liquids was slower than that of molecular solvents with similar
      polarity, indicating a greater degree of interactions between the ionic liquid
      ions and the zwitterionic MC isomer, which led to increased lifetimes for the MC
      ion complexes (19.6 s in acetonitrile and 90.9 s in [P6,6,6,14][NTf2]).
      Thermodynamic parameters of activation implied enhanced ordering of SO in ILs and
      its subsequent effect on thermal reversion of SO. Activation parameters found MC 
      -> SO relaxation was more temperature dependent in polar protic ILs such as
      [bmIm]+ than aprotic ILs such as [P6,6,6,14][NTf2] with deltaS++ values of 40 J K
      mol(-1) and -8.6 J K mol(-1), respectively. Activation energies were generally
      higher in ILs (83.9-97 kJ mol(-1)) compared to molecular solvents (67.8-89.8 kJ
      mol(-1)), which was reflected in longer lifetimes of MC due to greater energy
      barriers of relaxation to SO. Pre-metathesis cleaning of precursor salts was
      found to be necessary in order to obtain spectroscopic grade ILs for
      physicochemical analysis using solvatochromic probe dyes. Inconsistencies in the
      polarity-kinetic relationship further reinforced the belief that measuring
      polarity of ILs may not be possible with solvatochromic probe dyes.

PMID- 19842479
TI  - The UKB prescription and the heavy atom effects on the nuclear magnetic shielding
      of vicinal heavy atoms.
AB  - Fully relativistic calculations of NMR magnetic shielding on XYH3 (X = C, Si, Ge
      and Sn; Y = Br, I), XHn (n = 1-4) molecular systems and noble gases performed
      with a fully relativistic polarization propagator formalism at the RPA level of
      approach are presented. The rate of convergence (size of basis set and time
      involved) for calculations with both kinetic balance prescriptions, RKB and UKB,
      were investigated. Calculations with UKB makes it feasible to obtain reliable
      results for two or more heavy-atom-containing molecules. For such XYH3 systems,
      the influence of heavy vicinal halogen atoms on sigma(X) is such that heavy atom
      effects on heavy atoms (vicinal plus their own effects or HAVHA + HAHA effects)
      amount to 30.50% for X = Sn and Y = I; being the HAHA effect of the order of 25%.
      So the vicinal effect alone is of the order of 5.5%. The vicinal heavy atom
      effect on light atoms (HALA effect) is of the order of 28% for X = C and Y = I. A
      similar behaviour, but of opposite sign, is observed for sigma(Y) for which
      sigmaR-NR (I; X = C) (HAHA effect) is around 27% and sigmaR-NR(I; X = Sn) (HAVHA
      + HAHA effects) is close to 21%. Its electronic origin is paramagnetic for
      halogen atoms but both dia- and paramagnetic for central atoms. The effect on two
      bond distant hydrogen atoms is such that the largest variation of sigma(H) within
      the same family of XYH3 molecules appears for X = Si and Y = I: around 20%. In
      this case sigma(H; X = Sn, Y = I) = 33.45 ppm and sigma(H; X = Sn, Y = H) = 27.82
      ppm.

PMID- 19842480
TI  - Defect structure in lithium-doped polymer-derived SiCN ceramics characterized by
      Raman and electron paramagnetic resonance spectroscopy.
AB  - Lithium-doped polymer-derived silicon carbonitride ceramics (SiCN:Li) synthesized
      at various pyrolysis temperatures, have been investigated by means of
      multifrequency and multipulse electron paramagnetic resonance (EPR) and Raman
      spectroscopy in order to determine different defect states that may impact the
      materials electronic properties. In particular, carbon- and silicon-based
      'dangling bonds' at elevated, as well as metallic networks containing Li0 in the
      order of 1 microm at low pyrolysis temperatures have been observed in
      concentrations ranging between 10(14) and 10(17) spins mg(-1).

PMID- 19842481
TI  - The effect of Mn oxidation state on metal core electron excitations in manganese
      dimers: a time-dependent density functional investigation.
AB  - Time-dependent density functional theory (TDDFT) calculations have been performed
      on a series of manganese dimers with averaged metal oxidation states of 2.0, 2.5,
      3.0, 3.5 and 4.0. The excitation energies and oscillator strengths of transitions
      within the Mn K-core edges have been determined. The theoretical edge energies
      reproduce the experimental correlation between the relative position of the Mn K
      edge and the averaged Mn oxidation state extremely well. A comparison with the
      results obtained previously for Mn complexes with different ligand environments
      shows that TDDFT can be successfully applied to determine the relative edge
      energy differences between Mn systems, taking into account the various oxidation
      states of the metal and differences in ligand environment in a self-consistent
      manner. The accuracy of the calculated edge energies indicates that the
      methodology employed in the current study can be used to determine the oxidation
      states of Mn atoms in the Mn4Ca cluster of photosystem II (PSII).

PMID- 19842482
TI  - Theoretical study of the gas-phase ozonolysis of beta-pinene (C10H16).
AB  - The O3-initiated oxidation of beta-pinene, a monoterpene emitted in forested
      areas, was theoretically characterized using DFT, CBS-QB3 and CASPT2 quantum
      chemical calculations combined with statistical kinetic RRKM/master equation
      analysis and transition state theory. The first-principles based rate coefficient
      of the initial 03 attack on the exocyclic double bond shows a slight positive
      temperature dependence, k(tot)T = 1.27 x 10(-22) x T2.64 x exp(-714 K/T) cm3
      molecule(-1) s(-1) and is in close agreement with experiment. The resulting
      primary ozonides are found to give rise to two distinct, non-interconvertible
      conformers of the predominant Criegee intermediate (CI-1 and CI-2), with
      subsequent chemistries that are shown to be very different; this crucial aspect
      of beta-pinene ozonolysis was not taken into account in earlier studies. One of
      the conformers CI-2--carrying nearly half the total reaction flux--cannot undergo
      the usual "hydroperoxide channel", thus rationalizing why the OH yield from beta
      pinene is barely half of that from alpha-pinene. The predicted first-generation
      product distribution for atmospheric conditions is consistent with the available
      experimental data on the overall products. Our final results predict 5% of
      nopinone formation, 28% OH radicals with 2-oxo-alkyl radical coproducts, 37% of
      stabilized Criegee intermediates (SCI), 17% lactones, 10% CO2 formed after an
      intersystem crossing, and 3% of a newly proposed biradical formed from prompt
      ring opening in the CI. In atmospheric conditions, additional OH production is
      expected from the stabilized CI-1 conformer via the thermal unimolecular
      "hydroperoxide channel", whereas the stabilized CI-2 can react with H2O and its
      dimer, to produce additional nopinone. The expected subsequent chemistries of the
      large coproduct radicals formed from reactions of the two CI are also addressed
      in extenso.

PMID- 19842483
TI  - DFT 2H quadrupolar coupling constants of ruthenium complexes: a good probe of the
      coordination of hydrides in conjuction with experiments.
AB  - Transition metal (TM) hydrides are of great interest in chemistry because of
      their reactivity and their potential as catalysts for hydrogenation reactions. 2H
      solid-state NMR can be used in order to get information about the local
      environment of hydrogen atoms, and more particularly the coordination mode of
      hydrides in such complexes. In this work we will show that it is possible to
      establish at the level of density functional theory (DFT) a viable methodological
      strategy that allows the determination of 2H NMR parameters, namely the
      quadrupolar coupling constant (C(Q)) respectively the quadrupolar splitting
      (deltanuQ) and the asymmetry parameter (etaQ). The reliability of the method
      (B3PW91-DFT) and basis set effects have been first evaluated for simple organic
      compounds (benzene and fluorene). A good correlation between experimental and
      theoretical values is systematically obtained if the large basis set cc-pVTZ is
      used for the computations. 2H NMR properties of five mononuclear ruthenium
      complexes (namely Cp*RuD3(PPh3), Tp*RuD(THT)2, Tp*RuD(D2)(THT) and Tp*RuD(D2)2
      and RuD2(D2)2(PCy3)2) which exhibit different ligands and hydrides involved in
      different coordination modes (terminal-H or eta2-H2), have been calculated and
      compared to previous experimental data. The results obtained are in excellent
      agreement with experiments. Although 2H NMR spectra are not always easy to
      analyze, assistance by quantum chemistry calculations allows unambiguous
      assignment of the signals of such spectra. As far as experiments can be achieved
      at very low temperatures in order to avoid dynamic effects, this hybrid
      theoretical/experimental tool may give useful insights in the context of the
      characterization of ruthenium surfaces or nanoparticles with solid-state NMR.

PMID- 19842484
TI  - Electronic structure of Lewis acid sites on high surface area aluminium
      fluorides: a combined XPS and ab initio investigation.
AB  - High surface area (HS) A1F3 samples have been examined by X-ray photoelectron
      spectroscopy (XPS). The experimentally observed binding energy (BE) shifts were
      analysed by reference to core level BEs obtained from ab initio total energy
      calculations on a range of different, clean and hydroxylated alpha- and beta-A1F3
      surfaces. Examination of the two components visible in the A1 2p emission
      indicates that surface A13+ sites can, depending on the local geometric
      structure, contribute to both a high BE peak at 77.0 eV and a low BE peak at 76.1
      eV. Consequently, the areas under the peaks do not quantitatively correlate with
      surface area or Lewis acidity. However, a significant correlation between the
      number of surface A1 centres with dangling F or OH groups and the appearance of
      an A1 2p emission component at a BE lower than in the alpha-A1F3 bulk is
      predicted. The experimental F 1s emission data indicate that dangling F species
      are essentially absent. Examination of the O 1s emission suggests that HS A1F3
      handled at room temperature under any practical laboratory conditions, including
      glovebox environments, probably contains intrinsically a significant amount of OH
      groups and adsorbed water, which results in the covering of A1F3 surfaces by
      dangling or bridging OH groups. These Bronsted acid species must be removed by
      treatment at higher temperature before HS A1F3 reagents can fully develop their
      Lewis acidity.

PMID- 19842485
TI  - Electrochemistry of poly(3,4-ethylenedioxythiophene)-polyaniline/ Prussian blue
      electrochromic devices containing an ionic liquid based gel electrolyte film.
AB  - Electrochromic devices based on poly(3,4-ethylenedioxythiophene) (PEDOT) as the
      cathodic coloring electrode and polyaniline (PANI) or Prussian blue (PB) as the
      counter electrode containing a highly conductive, self-supporting, distensible
      and transparent polymer-gel electrolyte film encapsulating an ionic liquid, 1
      butyl-1-methylpyrrolidiniumbis-(trifluoromethylsulfonyl)imide, have been
      fabricated. Polarization, charge transfer and diffusion processes control the
      electrochemistry of the functional electrodes during coloration and bleaching and
      these phenomena differ when PEDOT and PANI/PB were employed alternately as
      working electrodes. While the electrochemical impedance response shows good
      similitude for PEDOT and PANI electrodes, the responses of PEDOT and PB were
      significantly different in the PEDOT-PB device, especially during reduction of
      PB, wherein the overall amplitude of the impedance response is enormous. Large
      values of the coloration efficiency maxima of 281 cm2 C(-1) (lambda = 583 nm) and
      274 cm2 C(-1) (lambda = 602 nm), achieved at -1.0 and -1.5 V for the PEDOT PANI
      and PEDOT-PB devices have been correlated to the particularly low magnitude of
      charge transfer resistance and high polarization capacitance operative at the
      PEDOT ionic liquid based electrolyte interface at these dc potentials, thus
      allowing facile ion-transport and consequently resulting in enhanced absorption
      modulation. Moderately fast switching kinetics and the ability of these devices
      to sustain about 2500 cycles of clear-to-dark and dark-to-clear without incurring
      major losses in the optical contrast, along with the ease of construction of
      these cells in terms of high scalability and reproducibility of the synthetic
      procedure for fabrication of the electrochromic films and the ionic liquid based
      gel electrolyte film, are indicators of the promise these devices hold for
      practical applications like electrochromic windows and displays.

PMID- 19842486
TI  - Electron energy loss spectroscopy and anion formation in gas phase coronene.
AB  - Electron collisions with gas phase coronene have been studied in the energy range
      0-80 eV to investigate electronic and pure vibrational excitations, as well as
      the anion formation near zero energy. Quantum chemical calculations using time
      dependent density functional theory (TDDFT) have been performed for an improved
      data analysis. Results have been obtained on both dipole allowed and forbidden
      transitions to low lying electronic excited states up to 8 eV, by varying the
      incident energy and scattering observation angle. Calculated values for
      excitation energies are in good agreement with experiment and with previous data.
      Pure vibrational excitation, performed with an energy resolution of 0.025 eV, is
      presented at incident energies from 1.5 to 9 eV. Five groups of excited
      vibrational modes are observed with energy losses ranging from 0.065 to 0.375 eV.
      Several resonant states appear to contribute to these excitations. Calculations
      of the harmonic vibrational frequencies of coronene, and determination of their
      main character, are used for the analysis of the results. The vertical electron
      affinity of coronene is calculated to be 0.45 eV in very good agreement with
      previous measured or calculated results. The parent anion (C24H12)- yield versus
      electron energy presents 2 peaks at zero and 0.30 eV (within 0.030 eV), in
      contrast with previous results where only one peak at zero was reported

PMID- 19842487
TI  - Hydrogen-induced mitigation of O on Ru(1010): a density-functional study.
AB  - The reaction of hydrogen with oxygen adsorbed on an Ru(1010) surface has been
      studied by density-functional calculations and kinetic Monte Carlo simulations.
      In agreement with experiment, it has been found that molecular hydrogen does not
      react with adsorbed O. In contrast, the hydrogenation of oxygen by an atomic H
      beam occurs spontaneously and results in the formation of adsorbed OH molecules.
      Subsequent impinging H-atoms can either initiate the formation of water, which
      readily desorbs at room temperature thus removing the O from the surface, or lead
      to formation and desorption of H2. It is the latter channel that hinders, at 300
      K, a complete removal of O from Ru capping layers on Si/Mo mirrors for extreme
      ultraviolet radiation. The estimated height of the barrier for the Langmuir
      Hinshelwood reaction between adsorbed H and OH, 0.92 eV, and related position of
      the H2O peak in model desorption spectra (approximately 320 K) are consistent
      with recent experiments. The H2 desorption peak appears at higher temperature,
      approximately 350 K, so that in the range from 320 to 330 K adsorbed hydrogen
      atoms will react predominantly with OH. Hence, the present simulations predict
      that an efficient removal of the chemisorbed O from Ru capping layers can be
      achieved by heating the surface to 320-330 K in a molecular hydrogen atmosphere.

PMID- 19842488
TI  - Evolution of the structures and stabilities of boron-doped lithium cluster
      cations: ab initio and DFT studies.
AB  - The lowest-energy structures and stabilities of the BLi(n)+ (n = 1-7) cluster
      cations are reported using the B3LYP, MP2, and CCSD(T) methods with the 6-311 +
      G(d) basis set. The first three-dimensional ground state in BLi(n)+ occurs for
      BLi5+ and the impurity, B atom, is seen to be trapped in an Li cage from BLi5+
      onwards. Significant changes occur for BLi(n)+ (n = 2-4) when compared with their
      corresponding neutral clusters. However, there is very little change between the
      geometries of neutral and charged clusters for BLi6+ and BLi7+. The evolution of
      the binding energies, vertical and adiabatic electron affinities, and
      dissociation enthalpies with the size of BLi(n)+, show an especial stability for
      BLi6+ among BLi(n)+ cluster cations. The unique stability of the 8-valence
      electron BLi6+ can be understood from the cluster electronic shell model (CSM).

PMID- 19842489
TI  - Divalent carbon atom as the proton acceptor in hydrogen bonding.
AB  - Proton-accepting properties of the divalent carbon atom in carbodiphosphoranes
      and their simple derivatives as well as in carbenes have been investigated. Both
      these groups of chemical compounds may be characterized by the formula CL2, where
      L is a sigma electron donor. Therefore, the carbon atom within both these
      systems, being in its atomic state, can have one or two lone electron pairs and,
      as a result, it may form hydrogen bonds of the type D-H...CL2, where C acts as a
      proton acceptor. Complexes of C(NH3)2, C(PH3)2, C[P(CH3)3]2, CF2, CCl2, and
      imidazol-2-ylidene with such proton donors as H2O, HCF3, HCN and HCCH have been
      analyzed by means of high-level quantum chemical methods. Density functional
      theory (DFT) and second-order Moller-Plesset (MP2) approaches have been applied
      in conjunction with the aug-cc-pVTZ basis set. The electron density distribution
      calculated by means of the atoms in the molecules procedure has also been
      analyzed. Proton-accepting properties of the carbon atom are discussed in detail.
      It is shown that the divalent carbon atom in the group of chemical systems
      investigated should be treated as a normal proton acceptor, similar to the much
      more electronegative O or N atoms. Moreover, hydrogen bonds of the type D-H...CL2
      within the complexes investigated have been found to be rather strong. The
      highest proton accepting ability of the carbon(0) atom found for the (NH3)2C
      derivative of carbodiphosphorane is explained on the basis of the Leffler-Hammond
      postulate. Within the group of carbenes, the strongest hydrogen bonds are formed
      by imidazol-2-ylidene. This is attributed to the significant aromatic character
      of the imidazol-2-ylidene ring that increases the proton-accepting properties of
      the carbene carbon atom.

PMID- 19842490
TI  - Frequency of negative differential resistance electrochemical oscillators: theory
      and experiments.
AB  - An approximate formula for the frequency of oscillations is theoretically derived
      for skeleton models for electrochemical systems exhibiting negative differential
      resistance (NDR) under conditions close to supercritical Hopf bifurcation points.
      The theoretically predicted omega infinity (k/R)1/2 relationship (where R is the
      series resistance of the cell and k is the rate constant of the charge transfer
      process) was confirmed in experiments with copper and nickel electrodissolution.
      The experimentally observed Arrhenius-type dependence of frequency on temperature
      can also be explained with the frequency equation. The experimental validity of
      the frequency equation indicates that 'apparent' rate constants can be extracted
      from frequency measurements of electrochemical oscillations; such method can aid
      future modeling of complex responses of electrochemical cells.

PMID- 19842491
TI  - Photoabsorption measurements and theoretical calculations of the electronic state
      spectroscopy of propionic, butyric, and valeric acids.
AB  - Absolute photoabsorption cross sections of propionic (C2H5COOH), butyric
      (C3H7COOH), and valeric (C4H9COOH) acids have been measured from the dissociative
      pi* <-- n(o) transition (beginning around 5.0 eV) up to 10.7 eV. This constitutes
      the first study of the neutral electronic states of propionic and butyric acids
      at energies above the pi* <-- n(o) band, while no previous spectroscopic data is
      available for valeric acid in the present range. The present assignments are
      supported by the first theoretical calculations of electronic transition energies
      and oscillator strengths for these organic acids. In addition, the excitation
      energies of the vibrational modes of propionic acid in its neutral electronic
      ground state and the vertical ionisation energies of all three molecules have
      been calculated for the first time. The He(I) photoelectron spectroscopy of
      propionic acid has been measured from 10 to 16 eV, revealing new fine structure
      in the first ionic band.

PMID- 19842492
TI  - The electronic structure and ionic diffusion of nanoscale LiTiO2 anatase.
AB  - Upon lithium insertion in the pristine TiO2 anatase phase the theoretical maximum
      of LiTiO2 can be reached in crystallite sizes less than approximately 10 nm,
      whereas bulk compositions appear limited to Li(x) approximately 0.6TiO2 at room
      temperature. Both X-ray absorption spectroscopy (XAS) and ab initio calculations
      have been applied to probe the electronic structure of the newly formed LiTiO2
      phase. These results indicate that a large majority of the Li-2s electrons reside
      at the Ti-3d(t2g)/4s hybridized site. About 10% of these electrons are
      transferred to non-localized states which makes this compound a good electronic
      conductor. Ionic conductivity is probed by nuclear magnetic resonance (NMR)
      relaxation experiments indicating relatively small hopping rates between the Li
      ion sites in LiTiO2. Formation of the poor ionic-conducting LiTiO2 at the surface
      of the particles explains why micro-anatase Li(x)TiO2 is not able to reach the
      theoretical maximum capacity at room temperature, and why this theoretical
      maximum capacity reached in nano-sized materials cannot be (dis)charged at high
      rates.

PMID- 19842493
TI  - Ice growth in supercooled solutions of a biological "antifreeze", AFGP 1-5: an
      explanation in terms of adsorption rate for the concentration dependence of the
      freezing point.
AB  - It is widely accepted, and we agree, that the lowering of the temperature at
      which ice can grow in a water solution of one of the biological antifreezes is a
      result of adsorption of the antifreeze molecules at the ice surface. However, how
      this can produce a well-defined "freezing point" that varies with the solution
      concentration has remained problematical. The results of a series of measurements
      of ice growing in supercooled solutions of an effective antifreeze are reported
      and interpreted in terms of this fundamental problem. It seemed that the solution
      of the problem would have to rely upon adsorption rate, because that appeared to
      be the only way for the concentration in solution to be so important. The crystal
      growth results are most unusual, and appear to confirm this. The growth rates
      over a wide range of antifreeze concentration in solution (about 0.05 to 9 mg ml(
      1)) are zero from the thermodynamic freezing point down to the "non-equilibrium"
      freezing point, where there is a very sudden increase to a plateau value that
      then remains about constant as the supercooling is increased by about 2 degrees
      C. The plateau values of growth rate are faster than those from pure water at the
      lower-supercooling ends of the plateaus, but slower at higher supercooling, until
      the growth rate starts rising toward that from pure water. These plateau values
      of growth rate increase markedly with increasing concentration of the antifreeze
      in solution. Along with these changes there are complex changes in the growth
      orientations, from c-axis spicules in the plateaus to those more characteristic
      of growth from pure water at greater supercooling. We conclude that the non
      equilibrium freezing point is determined by the adsorption rate. It is the
      warmest temperature at which the ice growth rate on the basal plane (where the
      antifreeze does not adsorb) is fast enough to prevent the area of basal face on a
      growing ice crystal from becoming too small to grow, which is determined in turn
      by the adsorption rate on non-basal surfaces, which is proportional to the
      solution concentration. This mechanism answers the question of how the antifreeze
      stops growth rather than how it prevents growth, a subtle but important
      difference.

PMID- 19842494
TI  - Surface photochemistry: alloxazine within nanochannels of Na+ and H + ZSM-5
      zeolites.
AB  - This work reports the surface photochemistry study of alloxazine adsorbed within
      nanochannels of MFI zeolites, namely in a series of Na+ and H+ ZSM-5 zeolites
      where the hydrophobic and hydrophilic character of the host varies
      systematically. Laser-induced room temperature and 77 K luminescence of air
      equilibrated solid powdered samples of alloxazine adsorbed onto the two sets of
      zeolites, which we will name NaZSM-5 and HZSM-5, revealed the existence of a
      single emission of alloxazine as a broad band centred at about 450 nm in some
      cases, while in others an emission with a maximum at about 510 nm was detected.
      The decay times of the alloxazine emission vary greatly going from solution to
      entrapment within the nanochannels of the ZSM-5 zeolites. In the latter case a
      lifetime distribution analysis has shown that the longest lifetime for the
      alloxazine fluorescence emission exists in the case where an isoalloxazine-type
      emission was detected, i.e. whenever the hydrophobic character of the host
      increases. Alloxazine entrapped in the more acidic zeolites exists in the form of
      emissive monomers. However, alloxazine emits both from monomeric and aggregated
      emissive forms in the case of the hydrophobic zeolites. These data indicate the
      formation of planar dimers of alloxazine whenever the number of active sites in
      the zeolite decreases. These dimers have to be formed at the intersections of the
      zig-zag and linear nanochannels of the zeolite since there is no space available
      for their formation inside the zeolite channels. The isoalloxazine tautomers are
      formed due to the existence of alloxazine dimers which may undergo double proton
      transfer in the excited state, following laser excitation. Delayed fluorescence
      of alloxazine was also detected for the HZSM-5 and NaZSM-5 entrapment both at
      room temperature and at 77 K. The present study is paradigmatic as regards the
      host influence on the photochemistry of the guest.

PMID- 19842495
TI  - Preparation, structure, and stability of Pt and Pd monolayer modified Pd and Pt
      electrocatalysts.
AB  - A controlled surface reaction technique has been successfully employed to prepare
      a series of Pt modified Pd/C (Pt/Pd/C) and Pd modified Pt/C (Pd/Pt/C) catalysts.
      The resulting catalyst materials were characterised by TEM, XRD,
      electrochemistry, and EXAFS techniques. In the case of the Pd/Pt/C carbon
      catalysts, core-shell structural arrangements were found, with a 0.04 A
      contraction of the Pd-Pd bond distance for the 1 Pd/Pt/C being observed. A
      greater degree of alloying was found for the Pt/Pd/C catalysts where the surface
      had a mixed composition with a large proportion of the Pt in the interior of the
      nanoparticle. However, strong Pt characteristics were exhibited in the
      voltammetry of Pt/Pd/C catalysts, most notably a large increase in the stability
      with respect to the electrochemical environment compared to Pd alone.

PMID- 19842496
TI  - EPR spectroscopic investigation of radical-induced degradation of partially
      fluorinated aromatic model compounds for fuel cell membranes.
AB  - EPR spectroscopic investigations of reactions between monomeric model compounds
      representing typical structural moieties of poly(aryl) ionomers and
      photochemically generated hydroxyl radicals are reported. Deoxygenated solutions
      of the model compounds (in a water/methanol mixture) containing hydrogen peroxide
      at defined pH values were exposed to UV light in the flow cell within the cavity
      of an EPR spectrometer. Spectra were analyzed by computer simulation and the
      formed radicals were assigned by comparing their g-factors and hyperfine coupling
      constants (hfccs) with those from the literature and from density functional
      theory (DFT) calculations. The relevance for polymer electrolyte membrane fuel
      cells (PEMFCs) and alkaline-anion exchange membrane fuel cells (AAEMFCs) is
      discussed.

PMID- 19842497
TI  - Density functional study of aurophilic interaction in [X(AuPH3)2+]2 (X = F, Cl,
      br, I).
AB  - Several closed-shell systems [X(AuPH3)2+]2 (X = F, Cl, Br, I) have been
      theoretically investigated by using density functional theory (DFT) and second
      order Moller-Plesset (MP2) methods in order to study the intermolecular
      aurophilic interaction. We studied the geometry of the structures, natural bond
      orbital (NBO) populations and the HOMO-LUMO gap of the title compounds.
      Experimental structural parameters of the title compounds were reproduced at the
      Xalpha level. The predicted experimental Au-F-Au and P-Au-F angles are 119.1 +/-
      0.5 degrees and 178.4 +/- 0.5 degrees, respectively. The intermolecular
      aurophilic interaction energy is decomposed and analyzed. The chemical
      deformation electronic density is obtained to analyze the intermolecular
      interaction.

PMID- 19842498
TI  - A stepwise atomic, valence-molecular, and full-molecular optimisation of the
      Hartree-Fock/Kohn-Sham energy.
AB  - A hierarchical optimisation strategy has been introduced for minimising the
      Hartree-Fock/Kohn-Sham energy, consisting of three levels (3L): an atom-in-a
      molecule optimisation, a valence-basis molecular optimisation, and a full-basis
      molecular optimisation. The density matrix formed at one level is used as a
      starting density matrix at the next level with no loss of information. To ensure
      a fast and reliable convergence to a minimum, the augmented Roothaan-Hall (ARH)
      algorithm is used in both the valence-basis and full-basis molecular
      optimisations. The performance of the ARH-3L method is compared with standard
      optimisation algorithms. Both for efficiency and reliability, we recommend to use
      the ARH-3L algorithm.

PMID- 19842499
TI  - Adsorption dynamics of H2 on Pd(100) from first principles.
AB  - We study H2 dissociative adsorption on Pd(100) through classical molecular
      dynamics (MD) calculations, using density functional theory (DFT) to describe the
      molecule-surface interaction potential. We employ two methods to evaluate the
      forces acting on the atoms along the trajectories: (i) by doing a DFT calculation
      (and using the Hellman-Feynman theorem) every time step, and (ii) by computing
      the gradient of a six-dimensional potential energy surface (PES) obtained first,
      by interpolation of DFT total energy results using the corrugation reducing
      procedure (CRP). The corresponding MD calculations, hereafter referred to as ab
      initio MD (AIMD) and CRP-PES-MD, respectively, provide very similar dissociative
      adsoption probabilities (P(diss)) as a function of the impact energy (E(i)) for
      initial rotational states characterized by 0 < or = J < or = 4 indicating that
      the interpolated CRP-PES gives a faithful representation of the underlying ab
      initio PES. Thus, we make use of the computationally cheaper CRP-PES-MD for a
      detailed analysis of rotational effects on dissociative adsorption for 0 < or = J
      < or = 12. In agreement with available experimental data for H2 interacting with
      Pd surfaces, we have found that P(diss) barely depends on J for E(i) > or = 200
      meV, and that it follows a non-monotonic J-dependence at low energies. Our
      simulations show that two competing dynamical effects which were previously
      suggested based on lower-dimensional model calculations are indeed also operative
      at low energies in a realistic high-dimensional treatment. For low values of J, a
      shadowing effect prevails that entails a decrease of Pdiss when J increases,
      whereas for J > 6, rotational effects are dominated by the adiabatic energy
      transfer from rotation to perpendicular motion that provokes the increase of
      Pdiss with increasing J.

PMID- 19842500
TI  - Direct spectroscopic detection of framework-incorporated vanadium in mesoporous
      silica materials.
AB  - Framework-incorporated vanadium mesoporous silica materials with different
      contents in vanadium were obtained by a facile, direct synthesis at room
      temperature, using VOSO4 x 5H2O as the vanadium precursor. The porous
      characteristics of the samples and the coordination environment of the vanadia in
      the structure were studied by a combination of techniques: X-ray diffraction, N2
      adsorption/desorption, FT-Raman, FTIR-PAS and UV-Vis-DR, electron paramagnetic
      resonance (EPR) and electron nuclear double resonance (ENDOR) spectroscopy. A
      structural comparison is made using pulsed EPR and ENDOR spectroscopic techniques
      between vanadia deposited on the surface of MCM-41 by the Molecular Designed
      Dispersion method and as-synthesised samples of vanadia incorporated in the
      mesoporous silica framework using the above-mentioned synthesis method. The EPR
      study on the non-calcined samples proves the incorporation of a high amount of
      vanadium in the silica framework by the observation of a strong hyperfine
      coupling of the unpaired electron with 29Si. It demonstrates the feasibility for
      EPR to reveal structural information on true incorporation of metal ions in
      framework positions leading to metal oxides.

PMID- 19842501
TI  - Adsorption of cyanodiacetylene on ice: a periodic approach.
AB  - The adsorption of cyanodiacetylene (HC5N) on ice has been investigated within a
      periodic approach at the density functional theory level using the parameter-free
      PBE0 hybrid functional. Two adsorption models, involving monodentate hydrogen
      bonding, have been considered. A third model, corresponding to a bridging binding
      model, has also been taken into account but found unstable. Calculations have
      been carried out considering two orientations of a proton-ordered model of ice
      surfaces, using two different unit cells in each case. Eight different cases of
      the adsorption of HC5N on ice have been investigated in depth at the geometric,
      energetic and electronic levels. Although HC5N is found to mainly bind to ice by
      direct hydrogen bonding, densities of states analysis suggest that its pi system
      plays a relevant role in the adsorption, especially by interaction with dangling
      surface hydrogen atoms, leading to significantly different adsorption geometries
      in all cases investigated. Analysis of the infrared spectral signature of HC5N
      shows the typical large red-shift of the H-C stretching mode frequency in the
      adsorption model involving hydrogen bonding between the H atom of HC5N and ice,
      in line with both experimental and previous theoretical findings based on cluster
      approaches.

PMID- 19842502
TI  - Infrared spectroscopy of 'forbidden' peptide sequences.
AB  - Certain pentapeptide sequences are absent from all known universal protein
      primary structures, even though they are found in the non-coding regions of DNA.
      These 'forbidden' sequences may have been rejected by evolution because they
      disrupt the formation of functional secondary protein structures. The uncapped
      pentapeptides FFMCT and WCFNL, which model the two 'most forbidden' sequences,
      were studied in a cold molecular beam using IR/UV holeburning spectroscopy, and
      DFT calculations were carried out to help reveal their inherent conformational
      preferences. Computed IR spectra for different structures were compared to the
      experimental IR spectra in the Amide I/II and Amide A vibrational band regions.
      The conformational assignments based on this analysis provide preliminary clues
      for understanding how these peptides may form structures that hinder the desired
      protein folding process. For FFMCT the structural analysis indicates a strong
      preference for a beta-turn conformation, where the C-terminal OH binds to the N
      terminal F side chain. The WCFNL results show that the peptide adopts a 3(10)
      helical conformation with free N- and C-termini, and less backbone hydrogen
      bonding than in FFMCT. Both structural motifs could drastically disturb the
      overall folding process when being part of a peptide or protein.

PMID- 19842503
TI  - With the presence of a lion...

PMID- 19842504
TI  - Health-care infrastructure: a sound investment.

PMID- 19842505
TI  - Assessing our impact over half a century.

PMID- 19842506
TI  - Practicum sheds new light on gerontology placements.

PMID- 19842507
TI  - Preparing students for the world.

PMID- 19842508
TI  - Coming of age.

PMID- 19842509
TI  - Waiting in line for healthcare.

PMID- 19842510
TI  - Career resiliency 101.

PMID- 19842511
TI  - Young leader looks forward to the future.

PMID- 19842512
TI  - Can we swing the pendulum back to centre?

PMID- 19842514
TI  - Reubenesque (sic)--pain's Mr Big.

PMID- 19842513
TI  - Greening perioperative care.

PMID- 19842515
TI  - Off target.

PMID- 19842516
TI  - Teamwork: how does this relate to the operating room practitioner?
AB  - Teamwork in the operating room is vital. We must view a picture of the evolving
      role of operating room practitioners and our educational needs. By raising our
      profile, we can encourage team work amongst multidisciplinary groups and secure
      the future of operating room practitioners in this complex matrix of patient
      care. With support we can create professional teams that will meet the values and
      expectations of trusts as well as government targets on a day to day basis.

PMID- 19842517
TI  - Thyroid eye disease.

PMID- 19842518
TI  - Non-steroidal anti-inflammatory drugs in orthopaedic and perioperative practice.
AB  - Non-steroidal anti-inflammatory drugs are powerful and effective anti
      inflammatory, analgesic and anti-pyretic drugs. They are routinely used in
      orthopaedic conditions and in the perioperative setting. They are however
      associated with potentially life-threatening side-effects and it is important to
      appreciate these before these medicines are administered. There is evidence
      suggesting that these drugs adversely affect bone formation, and this has
      implications for their use in patients with fractures and other pathologies that
      involve bone remodelling.

PMID- 19842519
TI  - Postoperative fluid and electrolyte balance: alarming audit results.
AB  - Perioperative fluid and electrolyte management requires an understanding of
      physiology and fluid losses. Consequences of poor management in postoperative
      patients can be fatal. This audit assesses the latest consensus guidelines and
      applies them to a district general hospital setting. Results are concerning and
      demonstrate a global lack of application of knowledge and understanding.
      Recommendations are suggested in order to control this potentially devastating
      situation.

PMID- 19842520
TI  - Traction splint: to use or not to use.
AB  - Traction splints are widely used for immobilisation of fractures of the lower
      limb. There is brevity of evidence-based research on their efficacy. We present a
      case of skin complication following traction splint for spiral fracture of femur.
      It is prudent to identify patients at higher risk of developing complications of
      immobilisation. In circumstances where delays are inevitable, the indication and
      appropriateness of continuation of traction splint should be re-evaluated.

PMID- 19842521
TI  - Clippers or the knife? The reform of surgical practice and the difficulty of
      early wound closure.
AB  - Salt, vinegar and wine sounds more like a recipe from the Saturday kitchen, but
      in 1667 it was all a surgeon could use to close wounds, along with silk and linen
      strips. In providing this service, barbers and surgeons found themselves confused
      and intertwined, struggling for professional recognition that was about to
      experience reform. Allegations of neglect in the aftermath of a major seafaring
      battle on the very shores of our capital city required the court of King Charles
      II to search for a solution of supreme magnitude to accommodate the hundreds of
      maimed sailors who were littering the streets of London. A campaign to conceal
      the horrors of warfare began which lead to the implementation of the Greenwich
      charter and the construction of a hospital which the architect Christopher Wren
      helped to design.

PMID- 19842522
TI  - Mary Seacole: self taught nurse and heroine of the Crimean War.
AB  - Mary Jane Seacole was born Mary Grant in Kingston Jamaica in 1805. Her father was
      a Scottish army officer and her mother a free Jamaican black, (slavery was not
      fully abolished in Jamaica until 1838). Her mother ran a hotel, Blundell Hall, in
      Kingston and was a traditional healer. Her skill as a nurse was much appreciated,
      as many of her residents were disabled British soldiers and sailors. It was from
      her mother that Mary learned the art of patient care, and she also assisted at
      the local British army hospital.

PMID- 19842523
TI  - Neurology requirements at Brown.

PMID- 19842524
TI  - The ignoble fate of the peppered moth.

PMID- 19842525
TI  - The Warren Alpert Medical School of Brown University: Class of 2009.

PMID- 19842526
TI  - Medical student education in refugee health and the concept of a medical home.

PMID- 19842527
TI  - Redesigning the clinical curriculum at the Warren Alpert Medical School of Brown
      University.
AB  - The proposed clinical curriculum in Years 3 and 4 provides the opportunity to
      complete the process begun with the reform of the pre-clerkship curriculum in
      2007. The redesign should produce an educational process which not only more
      adequately prepares students for the future, but helps produce leaders in
      multiple fields of medicine and re-establishes Brown as an innovator in medical
      education.

PMID- 19842528
TI  - Physician intervention for intimate partner violence.

PMID- 19842529
TI  - Barriers to healthcare access in the Southeast Asian community of Rhode Island.

PMID- 19842530
TI  - Upper and (old) lower facial (VII) nerve palsies on opposite sides.

PMID- 19842532
TI  - Physician's lexicon: epochs, eras and eons.

PMID- 19842531
TI  - Update on myelodysplastic syndrome.

PMID- 19842533
TI  - Resettlement of refugees from Africa and Iraq in Rhode Island: the impact of
      violence and burden of disease.

PMID- 19842534
TI  - Are males and females sexually abused as children socially anxious adults?
AB  - It is well documented that childhood sexual abuse is associated with deleterious
      outcomes in the areas of anxiety, depression, and sexual functioning. However,
      very little research has been conducted to specifically investigate childhood
      sexual abuse's relationship to adult social anxiety in both males and females.
      Participants included 250 undergraduate students from a large metropolitan
      university. Results indicated that almost one-third of males and a little over a
      third of females reported being sexually abused as a child or adolescent.
      Although a large portion of the sample exhibited socially anxious symptomology,
      childhood sexual abuse did not place males and females at increased risk for
      social anxiety. The use of a nonclinical, college student sample may provide
      researchers the opportunity to investigate resiliency in individuals with a
      history of childhood sexual abuse.

PMID- 19842535
TI  - Child sexual abuse, post-traumatic stress disorder, and substance use: predictors
      of revictimization in adult sexual assault survivors.
AB  - This study examined the unique effects of child sexual abuse simultaneously with
      post-traumatic stress disorder symptom clusters, problem drinking, and illicit
      drug use in relation to sexual revictimization in a community sample of female
      adult sexual assault victims. Participants (N=555) completed two surveys a year
      apart. Child sexual abuse predicted more post-traumatic stress disorder symptoms
      in adult sexual assault victims. Posttraumatic stress disorder numbing symptoms
      directly predicted revictimization, whereas other post-traumatic stress disorder
      symptoms (reexperiencing, avoidance, and arousal) were related to problem
      drinking, which in turn predicted revictimization. Thus, numbing symptoms and
      problem drinking may be independent risk factors for sexual revictimization in
      adult sexual assault victims, particularly for women with a history of childhood
      sexual abuse.

PMID- 19842536
TI  - The perils and possibilities in disclosing childhood sexual abuse to a romantic
      partner.
AB  - This study sought to understand the long-term effects of childhood sexual abuse
      (CSA) in adulthood by interviewing seven women about their experiences of
      disclosing CSA to romantic partners. Interpretative Phenomenological Analysis, an
      in-depth, qualitative research approach, was used to analyze the transcripts. The
      analysis produced 10 themes that were grouped into three domains: (a) Struggling
      in Private about Disclosure: prior to disclosing, participants described concerns
      that arose in the context of their romantic relationships; (b) The Experience of
      Disclosing: participants described when and how they disclosed and the thoughts
      and feelings accompanying disclosure; and (c) The Aftereffects of Disclosure:
      after disclosing, participants described the impact it had on the self as well as
      on the relationship with their romantic partner.

PMID- 19842538
TI  - Perceptions of child sexual abuse in a hypothetical cybersexploitation case: the
      importance of perpetrator honesty, outcome type, and respondent gender.
AB  - This study investigated perceptions of child sexual abuse in a hypothetical
      cybersexploitation case. Men were predicted to be more negative toward the victim
      than were women. Victims were predicted to be more negatively judged when they
      consented to sex than when they did not and when they were lied to than when they
      were not. Two hundred and seventy-six respondents read a sexual abuse depiction
      in which the perpetrator's disclosure about his age (being honest from the
      outset, lying, or refusing to disclose when questioned) and the final outcome of
      the meeting (consensual verses nonconsensual sexual intercourse) were varied
      between subjects. Respondents then completed a 17-item attribution scale. ANOVAs
      revealed broad support for the predictions. Results have implications for
      education about cybercrime.

PMID- 19842537
TI  - Prevalence of sexually abusive experiences in childhood and adolescence among a
      community sample of Latinas: a descriptive study.
AB  - This study examined the prevalence, severity, and circumstances of self-reported
      sexually coercive and abusive experiences in childhood and adolescence in a
      community sample of Latina women (N=204) ages 18 to 34 years. Results from
      structured phone interviews indicated that 35% of the women reported experiencing
      some form of sexual abuse, 31% of the reported perpetrators were family members,
      and 52% were boyfriends, friends, or acquaintances. Of those who reported an
      abusive experience, 44% had not disclosed the abuse to anyone; for those who did
      disclose, 74% reported feeling supported. Findings highlight the importance of
      including peer and dating-partner abuse in the assessment of CSA and the
      necessity for outreach to Latina women who may have never disclosed their
      experiences of abuse.

PMID- 19842539
TI  - Clerics who commit sexual offenses: offender, offense, and victim
      characteristics.
AB  - The aim of this investigation was to undertake an exploratory analysis of clerics
      who sexually offend and the circumstances related to these offenses. Thirty-three
      adult male religious leaders who had been charged with a sexual offense against a
      child or adolescent were included in the study. This study examined descriptive
      information about offenders, their victims, as well as characteristics of the
      crimes. Notable trends included the following: religious leaders tended to offend
      against boys living with both parents, the offense often took place at the
      clergy's residence, and the offense involved fondling the victim. The study also
      compared offenders with single versus multiple victims on crime variables and
      differences were noted with respect to victim access.

PMID- 19842540
TI  - Factors influencing the degree and pattern of parental involvement in play
      therapy for sexually abused children.
AB  - Although much has been written about the role of therapists in children's
      recovery from child sexual abuse, relatively little attention has been paid to
      the role of nonoffending parents. This study investigated the work of a team of
      therapists who sometimes included such parents in therapy sessions with children.
      The study sought to understand what factors were influencing the degree and
      pattern of parental involvement and to understand what effect these patterns of
      parental involvement were having on the process and outcomes of therapy. The
      study successfully identified a range of factors influencing the patterns of
      parental involvement, but more research will be needed to understand the effect
      on outcomes.

PMID- 19842541
TI  - Individual, team, and coach predictors of players' likelihood to aggress in youth
      soccer.
AB  - The purpose of this study was to examine personal and socioenvironmental factors
      of players' likelihood to aggress. Participants were youth soccer players (N =
      258) and their coaches (N = 23) from high school and club teams. Players
      completed the Judgments About Moral Behavior in Youth Sports Questionnaire
      (JAMBYSQ; Stephens, Bredemeier, & Shields, 1997), which assessed athletes' stage
      of moral development, team norm for aggression, and self-described likelihood to
      aggress against an opponent. Coaches were administered the Coaching Efficacy
      Scale (CES; Feltz, Chase, Moritz, & Sullivan, 1999). Using multilevel modeling,
      results demonstrated that the team norm for aggression at the athlete and team
      level were significant predictors of athletes' self likelihood to aggress scores.
      Further, coaches' game strategy efficacy emerged as a positive predictor of their
      players' self-described likelihood to aggress. The findings contribute to
      previous research examining the socioenvironmental predictors of athletic
      aggression in youth sport by demonstrating the importance of coaching efficacy
      beliefs.

PMID- 19842542
TI  - Parents' perceptions of child-to-parent socialization in organized youth sport.
AB  - The purpose of this study was to enhance understanding of how parents are
      socialized by their children's organized youth sport participation. Five
      semistructured focus groups were conducted with youth sport parents (N = 26) and
      analyzed using qualitative methods based on Strauss and Corbin (1998). Sixty
      three underlying themes reflected parents' perceived socialization experiences
      resulting from their children's organized youth sport participation. Each theme
      represented 1 of 11 subcategories of parental change, which were subsumed within
      four broad categories of parent sport socialization (behavior, cognition, affect,
      relationships). Each category of parental change was interconnected with the
      other three categories. Moreover, six potential moderators of parent sport
      socialization were documented, namely, child age, parent past sport experience,
      parent and child gender, child temperament, community sport context, and type of
      sport setting (individual or team). Together, these findings enhance
      understanding of parent sport socialization processes and outcomes, thus opening
      avenues for future research on parents in the youth sport setting.

PMID- 19842543
TI  - The effect of physical activity on executive function: a brief commentary on
      definitions, measurement issues, and the current state of the literature.
AB  - The purpose of the present commentary is to introduce relevant issues with
      respect to the measurement of executive function in physical activity studies.
      Suggested definitions of executive function are introduced, and executive
      function tasks that are commonly used in the neuropsychological literature are
      presented and briefly described. The extant literature on physical activity and
      cognition is discussed, and issues relative to the limitations of this body of
      literature are raised. In summary, research on the effect of physical activity on
      executive function is still in its infancy. We encourage researchers in this
      field to provide a clear definition of executive function, to carefully consider
      the relevance of published effect sizes to their own research questions, and to
      consider either providing a logical rationale for their selection of particular
      executive function measures or to use multiple measures of executive function
      when exploring relationships between physical activity and executive function.

PMID- 19842544
TI  - Test, revision, and cross-validation of the Physical Activity Self-Definition
      Model.
AB  - Structural equation modeling was used to test an extended version of the
      Kendzierski, Furr, and Schiavoni (1998) Physical Activity Self-Definition Model.
      A revised model using data from 622 runners fit the data well. Cross-validation
      indices supported the revised model, and this model also provided a good fit to
      data from 397 cyclists. Partial invariance was found across activities. In both
      samples, perceived commitment and perceived ability had direct effects on self
      definition, and perceived wanting, perceived trying, and enjoyment had indirect
      effects. The contribution of perceived ability to self-definition did not differ
      across activities. Implications concerning the original model, indirect effects,
      skill salience, and the role of context in self-definition are discussed.

PMID- 19842545
TI  - Illuminating the black box: investigating prefrontal cortical hemodynamics during
      exercise with near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) presents an appealing option for investigating
      hemodynamic changes in the cerebral cortex during exercise. This review examines
      the physical basis of NIRS and the types of available instruments. Emphasis is
      placed on the physiological interpretation of NIRS signals. Theories from
      affective neuroscience and exercise psychobiology, including Davidson's
      prefrontal asymmetry hypothesis, Dietrich's transient hypofrontality hypothesis,
      and Ekkekakis's dual-mode model, are reviewed, highlighting the potential for
      designing NIRS-based tests in the context of exercise. Findings from 28 studies
      involving acute bouts of exercise are summarized. These studies suggest that the
      oxygenation of the prefrontal cortex increases during mild-to-moderate exercise
      and decreases during strenuous exercise, possibly proximally to the respiratory
      compensation threshold. Future studies designed to test hypotheses informed by
      psychological theories should help elucidate the significance of these changes
      for such important concepts as cognition, affect, exertion, and central fatigue.

PMID- 19842546
TI  - Decision making in elite white-water athletes paddling on a kayak ergometer.
AB  - The present study investigated the effects of acute paddling on performance in a
      typical decision-making task. It was aimed at assessing whether the effects of
      moderate exercise can be replicated using the feet as response effectors when
      physical exercise essentially solicits upper-body muscles. Twelve national-level
      paddling athletes performed a Simon task while paddling at a moderate (75% of
      maximal heart rate, HRmax) and at very light (40% of HR(max)) intensities. The
      results showed that the effects of moderate exercise can be generalized to
      exercises involving different response effectors and upper-body muscle groups.
      They suggest (1) that the activation-suppression hypothesis (Ridderinkhof, 2002)
      holds when the task is performed with the feet, and (2) that moderate exercise
      speeds up reaction time and impairs the suppression of direct response
      activation.

PMID- 19842547
TI  - [Further discussion on postburn "shock heart " and its clinical significance].
AB  - A series of studies demonstrated that myocardial damage and cardiac dysfunction
      occur immediately after severe burn even before the intervention of significant
      reduction in blood volume as a result of increased capillary permeability.
      Because the heart is the power organ of the circulation, such myocardial damage
      and cardiac dysfunction lead not only to cardiac deficiency, it is also a
      precipitating factor of burn shock and ischemic/hypoxic injury. Therefore, we
      nominate this phenomenon as "shock heart". New measures including "volume
      replacement" plus "dynamic support" proposed according to this new recognition is
      of important clinical significance for burn shock resuscitation and prevention
      and treatment of ischemic/hypoxic injury, as well as reducing organ complications
      resulting from insufficient or excessive fluid resuscitation during early
      postburn stage.

PMID- 19842548
TI  - [Changes in B-type natriuretic peptide in plasma and its clinical significance in
      patients with severe burn during shock stage].
AB  - OBJECTIVE: To study the plasma content of B-type natriuretic peptide (BNP) in
      patients with severe burn during shock stage and probe its clinical significance.
      METHODS: Forty-two patients aged 18-60 years, with total burn surface area 30%
      TBSA or full-thickness burn area > or = 10% TBSA, hospitalized within 4 hours
      after burn, were divided into A group (with total burn surface area 30%-50% TBSA
      or full-thickness burn area 10%-20% TBSA, n = 21), and B group (with total burn
      surface area > 50% TBSA or full-thickness burn area > 20% TBSA, n = 21). Twenty
      patients admitted during the same time for plastic surgery were enrolled as
      control group. The plasma levels of BNP, creatine kinase (CK), CK-MB, troponin I
      (TnI) of all patients were determined on admission. The levels of BNP, TnI and
      fluid resuscitation volume were examined at 8, 16, 24, 48 post burn hour (PBH) in
      A and B groups. Analysis of correlation between BNP and fluid resuscitation
      volume was performed. RESULTS: On admission: BNP level in A group (68 +/- 19
      ng/L) and B group (99 +/- 38 ng/L), respectively, was increased as compared with
      that in control group (17 +/- 7 ng/L, P < 0.01). TnI level in A group (2.13 +/-
      0.67 microg/L) and B group (2.98 +/- 0.58 microg/L), respectively, was increased
      as compared with that in control group (0.12 +/- 0.03 microg/L, P < 0.01). There
      was no obvious difference in CK, CK-MB levels among A, B, and control groups (P >
      0.05). BNP levels in A, B groups continuously rose during 8-48 PBH, and they were
      positively correlated with fluid resuscitation volume. TnI level peaked at 24
      PBH, and decreased at 48 PBH. CONCLUSIONS: The plasma level of BNP is sensitive
      to reflect changes in myocardial ischemia and hypoxia as a rise in level of TnI
      in shock stage of severe burn, and it was positively correlated with fluid
      resuscitation volume. BNP can be used to guide fluid resuscitation during shock
      stage.

PMID- 19842549
TI  - [The role of CPI-17 in vascular calcium sensitivity regulated by protein kinase
      Calpha and Cepsilon in rats with hemorrhagic shock].
AB  - OBJECTIVE: To observe the role of PKC-potentiated inhibitory protein for protein
      phosphatase 1 of 17 x 10(3) (CPI-17) in vascular calcium sensitivity regulated by
      protein kinase Calpha (PKCalpha) and Cepsilon (PKCepsilon) in rats with
      hemorrhagic shock (HS). METHODS: Eight Wistar rats were used to reproduce 2 h HS
      model. Superior mesenteric artery (SMA) rings from HS rats were randomly divided
      into 2 h shock group (without treatment), PKCalpha agonist group (with addition
      of thymelea toxin into the nutrient solution), CPI-17 antibody + PKCalpha agonist
      group [incubation with thymelea toxin and CPI-17 antibody (1:800)], PKCepsilon
      agonist group (with addition of carbachol into the nutrient solution), and CPI-17
      antibody + PKCepsilon agonist group [incubation with carbachol and CPI-17
      antibody (1:800)]. SMA rings from another eight normal rats were used as normal
      control group. Calcium sensitivity indices (Emax, pD2) of SMA rings were measured
      by isolated organ perfusion system. Hypoxic VSMCs in primary culture were
      randomly divided into 2 h hypoxia group, PKCalpha agonist group (with above
      mentioned treatment), PKCepsilon agonist group (with above-mentioned treatment),
      normal VSMCs were used as normal control group. Protein expression and
      phosphorylation of CPI-17 were measured via Western blot. RESULTS: Emax and pD2
      in all the experimental groups were lower than those in normal control group (P <
      0.01). Emax in PKCalpha agonist group and PKCepsilon agonist group was increased
      (5.8 +/- 0.8, 5.8 +/- 0.9 mN, respectively) as compared with that of 2 h shock
      group (4.1 +/- 0.6 mN, P < 0.01). Protein expression and phosphorylation of CPI
      17 in VSMC were significantly decreased in 2 h hypoxia group, compared with those
      in normal control group (P < 0.05), and those in PKCalpha agonist and PKC agonist
      groups (P < 0.05 or P < 0.01). CONCLUSIONS: PKCalpha and PKCepsilon may regulate
      vascular calcium sensitivity through change in protein expression and activity of
      CPI-17 in HS rats.

PMID- 19842550
TI  - [Effect of "Xuebijing injection" on expression of high mobility group box-1
      protein and acute liver injury in rats with scald injury].
AB  - OBJECTIVE: To investigate the effect of "Xuebijing injection" (Xuebijing in
      brief) on expression of hepatic high mobility group box-1 protein (HMGB1) and
      acute liver injury in rats with scald injury. METHODS: Seventy-eight rats were
      divided into sham scald group (n = 18), scald group (n = 30), and Xuebijing
      treatment group (n = 30). Rats in the latter 2 groups were subjected to 30% full
      thickness scald injury followed with delayed resuscitation. These rats were
      sacrificed at 8th, 24th, and 72nd post-injury hour (PIH) to collect specimens.
      The hepatic pathological changes were observed. Serum levels of ALT and AST were
      detected. HMGB1 mRNA level in hepatic tissue was detected by the reverse
      transcription polymerase chain reaction. Protein relative expression quantity of
      HMGB1 in hepatic tissue was determined with Western blot and
      immunohistochemistry. Outcomes were denoted in integral absorbance ratio and
      absorbance value respectively. RESULTS: Massive infiltration of inflammatory
      cells in hepatic tissues was observed in scald group under light microscope,
      especially at 24th PIH, and it was decreased in quantity in Xuebijing treatment
      group. Compared with those of sham scald group, both mRNA and protein expressions
      of HMGB1 in hepatic tissue of scald group were significantly enhanced during 8-72
      PIH (P < 0.05 or P < 0.01), along with markedly increased serum levels of ALT and
      AST (P < 0.05 or P < 0.01). Compared with those in scald group at 24h and 72nd
      PIH, hepatic HMGB1 mRNA expressions (0.75 +/- 0.12 vs. 0.60 +/- 0.15 and 0.78 +/-
      0.11 vs. 0.55 +/- 0.07, respectively) and protein values (200 +/- 13 vs. 163 +/-
      13 and 175 +/- 14 vs. 160 +/- 16, respectively) in Xuebijing treatment group were
      markedly down-regulated (P < 0.05 or P < 0.01), and serum levels of ALT and AST
      decreased in different degrees (P < 0.05 or P < 0.01). CONCLUSIONS: HMGB1, the
      delay-appearing inflammatory mediator, is involved in the pathogenesis of
      inflammatory response in hepatic tissue in severely scalded rats. Treatment with
      Xuebijing can markedly down-regulate hepatic HMGB1 expression and protect liver
      against acute injury induced by delayed resuscitation.

PMID- 19842551
TI  - [Influence of myocardial inhibition on injury to liver, kidney and intestine at
      early stage in rat with severe scald].
AB  - OBJECTIVE: To investigate the influence of myocardial inhibition on injury to
      liver, kidney and intestine and blood perfusion at early stage in rat with severe
      burn. METHODS: Thirty-two healthy male Wistar rats were enrolled in the study and
      randomly divided into sham scald, propranolol, scald control and scald +
      propranolol groups, with 8 rats in each group. After intraperitoneal injection of
      10 g/L pentobarbital sodium for anesthesia, rats of the former two groups were
      sham scalded in a water bath of 37 degrees C for 18 s, while the latter two
      groups were inflicted with 30% TBSA full-thickness scald in a 97 degrees C water
      bath for 18 s. Rats were resuscitated with Ringer's lactate solution (4 mL x kg(
      1) x 1% TBSA(-1), i. p.) following the Parkland formula 30 mins after the injury.
      At the same time, rats in propranolol and scald + propranolol groups received
      propranolol 0.75 mg/kg intravenously. After 6 hours, parameters of myocardiac
      mechanics (SBP, DBP, MAP, LVSP, LVEDP, +/- dp/dt max) were recorded by the
      multiple channel physiological signal collecting and processing system; blood
      flow of liver, kidney and intestine were detected with the laser doppler
      flowmetry; the serum contents of cTnI, TBA, beta2-MG and DAO were determined for
      reflecting injuries to the heart, liver, kidney and intestine, respectively.
      RESULTS: Myocardiac mechanics parameters, with the exception of LVEDP, were
      decreased in propranolol group as compared with those in sham group (P <.05). All
      myocardiac mechanics parameters in burn control group were lower than those in
      sham group and higher than those in burn + propranolol group (P < 0.05). Blood
      flow of organs showed similar changes in above-mentioned 3 groups (P < 0.05).
      Organ damages as shown in burn control group [cTnI (4.86 +/- 0.29) microg/L, TBA
      (83.6 +/- 18.2) micromol/L, beta2-MG (2.75 +/- 0.19) mg/L, DAO (1.45 +/- 0.09) x
      10(3) U/L] were more serious than those in sham control group [cTnI (1.73 +/-
      0.09) microg/L, TBA (24.5 +/- 2.4) micromol/L, beta2-MG (1.15 +/- 0.18) mg/L, DAO
      (0.87 +/- 0.13) x 10(3) U/L], and less serious than those in scald + propranolol
      group [cTnI 5.95 +/- 0.42 microg/L, TBA 125.8 +/- 21.3 micromol/L, beta2-MG 3.25
      +/- 0.17 mg/L, DAO (1.83 +/- 0.13) x 10(3) U/L] (P < 0.05). CONCLUSIONS:
      Propranolol can aggravate injury to the liver, kidney and intestine at early
      stage in rat with severe burn, suggesting that "shock heart" may be one of
      initial factors in lowering blood flow to the organs, thus inducing injury to
      them.

PMID- 19842552
TI  - [Effects of angiotensin (1-7) and enalaprilat on function of isolated rat heart
      perfused by burn serum].
AB  - OBJECTIVE: To investigate effects of angiotensin (1-7) [Ang (1-7)] and
      enalaprilat on function of isolated rat heart perfused by burn serum. METHODS:
      Eighty SD rats were used to prepare burn serum. Hearts of another 24 SD rats were
      isolated to reproduce Langendorff perfusion model. The rat hearts were divided
      into different groups with different perfusion fluids as K-H buffer group, K-H
      buffer containing 20% burn serum group (burn serum group), K-H buffer containing
      20% burn serum and 2 microg/mL enalaprilat group (enalaprilat group), and K-H
      buffer containing 20% burn serum and 1 nmol/mL Ang (1-7) group [Ang(1-7) group].
      The rat hearts were perfused for 30 mins with each of above-mentioned fluids in
      different groups. Then left ventricular systolic pressure (LVSP), left
      ventricular end diastolic pressure (LVEDP), +/- dp/dt max, coronary flow(CF),
      level of creatine kinase (CK) and lactate dehydrogenase (LDH) in respective
      coronary effluent were determined. RESULTS: Compared with LVSP (11.2 +/- 1.0 kPa,
      1 kPa = 7.5 mm Hg), +dp/dt max (642 +/- 53 kPa/s), -dp/dt max (380 +/- 61 kPa/s)
      and CF level in K-H buffer group, CF, LVSP (5.9 +/- 0.8, 8.0 +/- 1.1, 8.9 +/- 1.3
      kPa, respectively), +dp/dt max (275 +/- 37, 454 +/- 48, 479 +/- 63 kPa/s,
      respectively), -dp/dt max (135 +/- 35, 219 +/- 47, 277 +/- 58 kPa/s,
      respectively) of burn serum group, those levels in Ang (1-7) group, and
      enalaprilat group were decreased obviously (P < 0.05 or P < 0.01), but LVEDP,
      level of CK and LDH in coronary effluent were increased. Compared with those
      parameters in burn serum group, CF, LVSP, +/- dp/dt max of Ang (1-7) group and
      enalaprilat group were increased obviously (P < 0.05 or P < 0.01), and LVEDP,
      level of CK and LDH in coronary effluent were decreased obviously (P < 0.01).
      CONCLUSIONS: Ang (1-7) and enalaprilat can effectively improve left ventricular
      function of isolated rat heart perfused by burn serum and mitigate myocardial
      injury.

PMID- 19842553
TI  - [Effect of oral fluid resuscitation on pulmonary vascular permeability and lung
      water content in burn dogs in shock stage].
AB  - OBJECTIVE: To investigate the effect of oral fluid resuscitation on pulmonary
      vascular permeability and lung water content in burn dogs during shock stage.
      METHODS: Eighteen male Beagle dogs with catheterization of carotid artery and
      jugular vein for 24 hours were subjected to 50% TBSA full-thickness burn, then
      they were divided into non-fluid resuscitation (NR), oral fluid resuscitation
      (OR), intravenous fluid resuscitation (IR) groups, with 6 dogs in each group.
      Dogs in OR and IR groups were given glucose-electrolyte solution (GES) by gastric
      tube or intravenous infusion according to Parkland formula within 24 hours after
      burn, while those in NR group were not given any treatment. Dogs in each group
      were then given intravenous fluid for further resuscitation after 24 post burn
      hours (PBH). Deaths were recorded within 72 hours after burn. Mean arterial
      pressure (MAP), respiratory rate (RR), PaO2, extravascular lung water index
      (ELWI) and pulmonary vascular permeability index (PVPI) were determined before
      burn and at 30 mins and 4, 8, 24, 48, 72 PBH with the aid of PICCO. Dogs were
      sacrificed to collect lung tissue for determination of water content at 72 PBH or
      just before death. RESULTS: All dogs died during 9-22 PBH in NR group, 3 dogs
      died during 25-47 PBH in OR group, and all dogs survived within 72 PBH in IR
      groups. Compared with those before burn, RR (44.0 +/- 5.0) times/min, ELWI (10.3
      +/- 0.6) mL/kg and PVPI (6.6 +/- 0.6) were markedly increased in NR group at 8
      PBH, but PaO2 and MAP were obviously decreased (P < 0.05). In OR group, RR (33.0
      +/- 4.0) times/min, ELWI (8.9 +/- 0.3) mL/kg and PVPI (5.7 +/- 0.4) were
      significantly lower than those of NR group (P < 0.05), but higher than those of
      IR group [RR (26.0 +/- 3.0) times/min, ELWI (8.2 +/-0.3) mL/kg, PVPI (4.2 +/-
      0.4), P < 0.05] at 8 PBH. PaO2 and MAP in OR group were higher than that in NR
      group (P < 0.05). Lung water content showed no statistically significant
      difference between OR ang IR groups (P > 0.05), which were lower than that in NR
      group (P < 0.05). CONCLUSIONS: Although the protective effect of oral fluid
      resuscitation with GES on the lung of burn dog at shock stage was inferior to
      intravenous fluid, it still can decrease pulmonary vascular permeability,
      alleviate pulmonary edema, and reduce pulmonary complication compared with no
      resuscitation with fluids.

PMID- 19842554
TI  - [Reproduction of a model of heat injured keratinocyte in vitro and observation on
      its apoptosis rate].
AB  - OBJECTIVE: To reproduce a model of heat injured KC in vitro and explore its
      apoptosis rate of KC due to heat injury at different temperature. METHODS: Human
      KCs were cultured in vitro, and they were incubated at 37, 41, 43, 45, 48, and 51
      degrees C respectively for 10 mins in water bath. Trypan blue staining and
      Hoechst 33258 fluorescence staining were used respectively to determine necrosis
      and apoptosis of KC. Rates of apoptosis and necrosis of KC were analyzed
      quantitatively by flow cytometer. The proliferation activity of KC after heat
      injury was detected by MTT test. RESULTS: The results of trypan blue staining,
      Hoechst 33258 fluorescence staining, and flow cytometer demonstrated that number
      of apoptotic and necrotic KC increased gradually along with a rise of water bath
      temperature. The rates of apoptosis and necrosis of KC were respectively (12.3 +/
      3.2)% and (14.1 +/- 1.6)% at 45 degrees C, (27.7 +/- 5.1)% and (58.0 +/- 4.2)%
      at 48 degrees C. Rate of KC necrosis reached up to (83.0 +/- 5.3)% at 51 degrees
      C. Inhibition of KC growth reached a stationary phase when the injurious
      temperature reached 45 degrees C as observed with MTT test. CONCLUSIONS: Heat
      injury can induce apoptosis and growth inhibition of KC in vitro. Incubating KC
      at 45 degrees C for 10 mins is a good condition to reproduce a model of heat
      injured KC in vitro. This model may be used to study the biological character and
      apoptosis of KC after burn injury.

PMID- 19842555
TI  - [Study on endoplasmic reticulum stress and injury to basic function unit of
      colonic motility in rats with scald injury].
AB  - OBJECTIVE: To observe expressions of glucose-regulated protein (GRP78) and
      caspase-S12 in nervous system-interstitial cells of Cajal (ICC) in smooth muscle
      in colonic wall in rats with scald injury, as well as their relevant
      ultrastructural changes, so as to probe the possible mechanisms of dynamic damage
      in murine colon after a scald injury. METHODS: Fifty healthy Sprague-Dawley rats
      were randomly divided into scald (n = 40) and control (n = 10) groups. Rats in
      scald group were inflicted with 30% TBSA full-thickness scald, and received an
      intraperitoneally injection of Ringer lactate solution (50 mg/kg) for
      resuscitation, while those in control group had similar treatment with the
      exception of scald. Rats in control group and scald group were sacrificed at 3,
      6, 12, 24 post scald hour (PSH, 10 rats at each time point) for collection of 4
      cm of colonic tissue, 5 cm proximal to the cecum. A segment of colonic wall, 1 cm
      in length, was obtained from the middle of the harvested segment of colon, and it
      was fixed with 3% glutaraldehyde or 10% formaldehyde. The samples fixed with
      glutaraldehyde were used to observe ultrastructural alterations under
      transmission electron microscope, while that with formaldehyde were used to
      observe expressions of GRP78 and caspase-12 in colonic wall by
      immunohistochemical assay. RESULTS: The colonic smooth muscle cells of rats in
      control group showed regular arrangement, their organelles were abundant, nucleus
      centrally located, euchromatin distributed evenly with more abundant
      mitochondrial cristae and less smooth endoplasmic reticulum, neuronal organelles
      were abundant in intermuscular plexus, and ICC could be seen in the neighborhood
      of neurons. The colonic smooth muscle cells appeared in irregular and disordered
      manner in scald group, perinuclear space was widened, intercellular vacuoles were
      observed, mitochondria showed vacuolation degeneration with dissolved and
      condensed cristae, rough endoplasmic reticula were dilated with partial
      dissolution, and perinuclear cytoplasm of ICC was obviously decreased. The
      expression of GRP78 was increased in scald group at 3, 6, 12 PSH (4.3 +/- 0.9,
      6.0 +/- 0.7, 4.8 +/- 1.1 score) as compared with that in control group (2.4 +/-
      0.7 score, P < 0.05). The expression of caspase-12 in scald group at 6, 12, 24
      PSH was higher than that in control group (P < 0.05). GRP78 was consistently
      expressed in cytoplasm in control group, while in scald group, it mainly appeared
      in mucosa, myenteric plexus, and stromal cells, but only moderately or lightly
      expressed in smooth muscle cells. The expression of GRP78 was positive in scald
      group at 3, 6, 12 PSH, strongly positive at 6 PSH, and it was also expressed in
      cytoplasm in control group. The expression of caspase-12 in scald group was not
      obviously positive at 3 PSH, and weakly positive at 6, 24 PSH, but strongly
      positive at 12 PSH, while no expression was shown in control group. CONCLUSIONS:
      Marked pathological changes are observed in enteric nervous system-interstitial
      cells of Cajal-smooth muscle in rats with severe scald injury. It may be related
      with cellular injuries induced by caspase-12 apoptotic pathways through activated
      endoplasmic reticulum stress.

PMID- 19842556
TI  - [An experimental study of using chitinous membrane as the culture scaffold for
      epidermal stem cells].
AB  - OBJECTIVE: To investigate the feasibility of constructing a skin tissue
      engineering covering on chitinous membrane using rat epidermal stem cells (ESCs).
      METHODS: Rat ESCs were isolated and cultured by cold digestive method and
      collagen type IV adherent method. Cell colonies were observed with inverted
      microscope. Expressions of DNA and RNA of ESCs were detected with laser scanning
      confocal microscope. Growth curves of cells were determined with Alamar BlueTM
      colorimetric method. Expressions of surface markers of ESCs (CD29, CD71, CD49d,
      and CD34) were detected with flow cytometer. Positive expressions of CK15, CK19,
      and P63 of ESCs were determined by immunohistochemistry. Influence of original
      chitinous membrane leachate in different dilutions on ESCs was observed.
      Condition of growth of ESCs on the vehicle was observed. RESULTS: Isolated
      cultured cells were verified as ESCs, of which the doubling generation time was
      48 hs. CD29 and CD49d were positive; CD71 and CD34 were negative; CK19, CK15, and
      P63 were positive. Compared with that of control group, ESCs cultured in
      chitinous membrane leachate showed slight cell proliferation when diluted to 1:8
      1:512 dilutions, but there was no statistically significant difference (P >
      0.05). The checkerboard-form cell colonies of ESCs could be visualized with naked
      eyes on the chitinous membrane in 2-4 weeks of culture. A multitude of ESCs were
      seen to grow on fibres under microscope. CONCLUSIONS: Chitinous membrane may be
      used as ESCs culture vehicle, and biological compatibility is good.

PMID- 19842557
TI  - [Proteomic change in lymphocytes of scalded rabbits caused by Staphylococcus
      aureus invasion].
AB  - OBJECTIVE: To study the proteomic change in lymphocytes of rabbits with scald
      injury and Staphylococcus aureus (SA) invasion. METHODS: Twenty-four rabbits were
      divided into four groups as follows: control group, scald group, scald with SA
      invasion 2 hs group, and scald with SA invasion 6 hs group, according to random
      number table, with 6 rabbits in each group. Except for rabbits in control group
      (sham scald at 37 degrees C), rabbits in the other 3 groups were subjected to 30%
      TBSA full-thickness scald. Rabbits in SA invasion 2 and 6 hs groups were injected
      with 2 mL (1.0 x 10(8) CFU/mL) SA suspension, which was in the log growth phase,
      via auricle vein 18 hs and 22 hs after injury. Whole blood samples were collected
      from carotid artery of rabbits in 4 groups 24 hs after scald. Lymphocytes were
      isolated and its extracted proteins were analyzed by two-dimensional gel
      electrophoresis coupled with mass spectroscopy. RESULTS: About 1030 protein spots
      of lymphocytes were detected in each group. Compared with that of control group,
      19 protein spots were found to be differentially expressed in the other 3 groups,
      and 11 spots (10 proteins) were identified. Expression levels of cofilin,
      cyclophilin A, ubiquitin, nucleoside diphosphate kinase, glutamate dehydrogenase
      and annexin 1 were down-regulated, but expression level of peroxiredoxin was up
      regulated obviously. CONCLUSIONS: There is obvious proteomic change in
      lymphocytes of scalded rabbits or of scalded rabbits invaded by SA, and it may
      relate to immune suppression and sepsis after injury.

PMID- 19842558
TI  - [Effect of burn blister fluid on human mesenchymal stem cell (MSC) in vitro and
      its phenotypic modulation in culture].
AB  - OBJECTIVE: To study the effect of blister fluid obtained from burn patient on
      human MSCs in vitro and its phenotypic modulation in culture. METHODS: Blister
      fluid from burn patients was collected at 12, 24, 48 post burn hour (PBH). The
      human MSCs were isolated, cultured, amplified and identified in vitro, then were
      divided into A (culture with 20% blister fluid collected at 12 PBH) , B (culture
      with 20% blister fluid collected at 24 PBH), C (culture with 20% blister fluid
      collected at 48 PBH), N (with ordinary culture medium) groups. The growth of MSCs
      and micro-organisms in blister fluid were observed. Positive expression rates of
      CD44 and CK7 were detected by flow cytometry after culture for 8 days. RESULTS:
      Bacterial and fungal growths were absent in 15 blister fluid samples. There was
      no obvious change in MSC morphology in each group. Compared with that of N group,
      the number of MSCs in A, B, C groups was decreased, especially in C group. CD44
      positive expression rate in A, B, C groups was (83.0 +/- 3.1)%, (77.2 +/- 2.9)%
      and (65.1 +/- 2.3)%, respectively,which was obviously lower than that in N group
      [(89.5 +/- 3.2)%, P < 0.01]. CK7 positive expression rate in A, B, C groups was
      (24.06 +/- 0.11)%, (16.41 +/- 0.09)% and (4.48 +/- 0.07)%, respectively, which
      was obviously higher than that in N group [(3.87 +/- 0.04)%, P < 0.01].
      CONCLUSIONS: Burn blister fluid can obviously inhibit the growth of human MSC
      cultured in vitro, and may promote modulation of its phenotype to certain extent.

PMID- 19842560
TI  - [Effects of intensive insulin therapy on inflammatory response and prognosis of
      patients with severe trauma].
AB  - OBJECTIVE: To investigate the effects of intensive insulin therapy on
      inflammatory response and prognosis of patients with severe trauma. METHODS:
      Eighty severely injured patients were divided into intensive insulin therapy
      group (n = 40, IT) and routine therapy group (n = 40, RT) in random pair. At the
      time of admission, a continuous infusion of insulin (2-4 U/h) was pumped into the
      patients of IT group to maintain blood glucose level at 6-8 mmol/L. Patients in
      RT group were given routine treatment without administration of insulin. Fever,
      organ injury, and mortality of patients in 2 groups were recorded. Venous blood
      was drawn from patients of 2 groups on the morning of post treatment day (PTD) 1,
      3, 5, and 7. Values of TNF-alpha, C-reactive protein (CRP), IL-2, and IL-10 in
      plasma were assayed. RESULTS: High fever appeared in 9 patients in IT group, and
      WBC exceeded 10.0 x 10(9) for more than 3 days in 17 patients in this group,
      versus 20 and 29 patients respectively in RT group. Dysfunction of 1 organ
      appeared in 31 patients in IT group and 30 patients in RT group. Dysfunction of 3
      organs appeared in 10 patients in IT group and 19 patients in RT group.
      Dysfunction of 4 organs appeared in 7 patients in IT group and 12 patients in RT
      group. In IT group, 4 patients died within 3 post-injury day (PID), and 1 patient
      died after PID 3 (total case fatality: 12.5%). In RT group, 5 patients died
      within 3 PID, and 4 patient died after PID 3 (total case fatality: 22.5%). Plasma
      levels of TNF-alpha and CRP of patients in IT group were significantly lower than
      those of patients in RT group on PID 3-7 ( P < 0.05 or P < 0.01), while levels of
      IL-2 and IL-10 of patients in IT group were significantly higher than those of
      patients in RT group (P < 0.05 or P < 0.01). Plasma levels of TNF-alpha (1.3 +/-
      0.6 microg/L) and CRP (55 +/- 16 mg/L) of patients in IT group on PTD 7 were
      lowered to the trough level, and they were significantly lower than those of
      patients in RT group (3.0 +/- 0.8 microg/L, 89 +/- 20 mg/L, respectively, P <
      0.01). CONCLUSIONS: Intensive insulin therapy can mitigate systemic inflammatory
      response and improve prognosis of patients with severe trauma.

PMID- 19842559
TI  - [Effects of arginine enriched enteral nutrition on nutritional status and
      cellular immunity in burn patients].
AB  - OBJECTIVE: To investigate the effects of arginine enriched enteral nutrition (EN)
      on nutritional status and cellular immunity of severely burned patients. METHODS:
      Randomized, single blind, parallel and positive control investigation was
      employed in the study. Thirty severely burned patients were divided into enteral
      immune nutrition (EIN) group and EN group. Sixteen patients in EIN group received
      enteral nutrition enriched with arginine, while the other 14 patients in EN group
      received standard enteral nutrition. Nutritional support was continued for 14
      days. Gastrointestinal reaction of patients in 2 groups was observed. Fasting
      venous blood was drawn from patients of both groups before receiving nutrition
      treatment and on the morning of 7th, 14th day of treatment. Level of serum
      protein, hepatic function parameters, renal function parameters, fasting-blood
      glucose, and subpopulations of T lymphocytes in peripheral blood were determined.
      RESULTS: (1) Incidence of gastrointestinal side effect in EIN group (25.0%) was
      close to that of EN group (21.4% , P > 0.05). (2) Compared with pre-treatment
      days, levels of prealbumin and transferrin in serum of patients in 2 groups on
      7th and 14th post-treatment days were significantly increased (P < 0.05 or P <
      0.01), but there was no significant difference between 2 groups. The level of
      total serum protein on 14th day of treatment of patients was significantly
      increased in both groups, and that of EIN group (66 +/- 7 g/L) was significantly
      higher compared with that in EN group (64 +/- 11 g/L, P < 0.05). The level of
      serum albumin (29 +/- 5, 32 +/- 5 g/L, respectively) of patients in EIN group on
      7th and 14th day of treatment were significantly higher than that (26 +/- 4 g/L,
      P < 0.05) in pre-treatment days, however there was no significant difference in
      EN group. (3) There was no significant difference in respect of hepatic function,
      renal function, and fasting-blood glucose between pre-treatment and post
      treatment periods in both groups (P > 0.05). (4) The ratio of CD4(+), CD8(+) on
      14th day of treatment in EIN group was close to that of pretreatment level. In EN
      group, cell percentage of CD4(+) significantly decreased, while that of CD8(+)
      significantly increased (P < 0.05), and CD4(+) was significantly higher [(56 +/-
      8)%] in EIN group than that in EN group [(55 +/- 12)%, P < 0.05]. In both groups,
      cell percentage of CD3(+) was significantly higher than that in pre-treatment
      days (P < 0.05), while there was no obvious change in CD4(+)/CD8(+). CONCLUSIONS:
      Arginine enriched enteral nutrition can effectively improve nutritional status
      and cellular immune function of burn patients.

PMID- 19842561
TI  - [Effect of different dressing materials in various combinations on wound
      microenvironment of donor site in burn patients].
AB  - OBJECTIVE: To investigate the effect of dressing materials in various
      combinations on burn wound microenvironment and healing condition. METHODS: Two
      hundred donor sites with wounds of 0.3 mm in depth in 186 burn patients, who
      needed skin grafting and admitted to our ward were enrolled in study, and they
      were divided into A (with dressing composed of alginate + cotton pad for donor
      area), B (with dressing composed of vaseline gauze + cotton pad for donor area),
      C (with dressing composed of alginate + foam dressing for donor area), D (with
      dressing composed of vaseline gauze + foam dressing for donor area) groups
      according to random table method. Effect of dressings on wound evaporation and pH
      value were observed. Bacterial colonization, degree of pain complained by
      patients after dressing change, and wound healing time in each group were
      compared. RESULTS: One hundred and eighty-four patients complied with the study,
      while 2 patients were excluded due to untimely falling-off of the dressing. Wound
      evaporation in A, B, C, D groups was (35.5 +/- 3.2), (31.3 +/- 2.8), (23.1 +/-
      2.9), (18.1 +/- 2.3) mL x h(-1) x m(-2) respectively, among them B group showed
      optimal effect of keeping humidity (P < 0.01). Wound pH value in A, B, C, D
      groups was 7.22 +/- 0.06, 7.41 +/- 0.03, 7.05 +/- 0.03, 7.34 +/- 0.06,
      respectively, among them it was highest in B group. The positive rate of bacteria
      in D group was highest (22.4%), and lowest in C group (4.0%). Pain was lightest
      in C group (score was 0.98 +/- 0.12), and most serious in B group (score was 8.14
      +/- 0.82). The shortest wound healing time was seen in C group (6.7 +/- 0.8 d),
      and longest in D group (15.6 +/- 3.5 d). CONCLUSIONS: Application of various
      dressings on similar wounds can produce different wound microenvironment, which
      is closely related to wound healing time. Compared with pH value, humidity is the
      more important factor for wound healing.

PMID- 19842562
TI  - [Expression of neuroglobin in rats with brain injury induced by LPS].
AB  - OBJECTIVE: To investigate the expression of neuroglobin (Ngb) in frontal cortex,
      cerebrospinal fluid (CSF) and serum in rats with brain injury induced by LPS and
      to elucidate its significance. METHODS: Seventy adult Sprague-Dawley rats were
      randomly divided into LPS (n = 60, with injection of 0.1 mg/kg LPS into cistern)
      and control (C, n = 10, with injection of equal volume of isotonic saline into
      cistern) groups, with 10 rats in each group. The plasma, CSF as well as frontal
      cortex from sacrificed rats were collected in LPS group at 3, 6, 12, 24, 48, 72
      post injection hour (PIH), with 10 rats at each time point. The protein
      expression of Ngb was measured by enzyme-linked immunosorbent assay (ELISA) and
      Western blot. Expression of Ngb in frontal cortex was determined by SP. Water
      content of frontal cortex was assessed by drying method. The correlation among
      Ngb contents in serum, CSF, frontal cortex and water content of frontal cortex
      was analyzed with multiple comparison. RESULTS: Ngb expression (by ELISA): Ngb
      expression of frontal cortex, CSF, and serum in LPS group was higher than that in
      C group at each time point, and it peaked at48 PBH (35.4 +/- 3.9, 22.7 +/- 3.1,
      14.4 +/- 2.8 ng/mL, respectively, P < 0.01). Ngb expression (by Western blot):
      Ngb protein with relative molecular mass of 17 x 10(3) was observed in each
      group. Ngb expression detected by Western blot was similar to that detected by
      ELISA. Brain water content was significantly greater in LPS group than that of C
      group at 6-72 PIH (P < 0.01), and it peaked at 48 PBH (83.3 +/- 1.9)%. Ngb
      contents in serum, CSF, frontal cortex, and water content of frontal cortex were
      positively correlated with multiple comparison ( y = 0.631-0.719, P < 0.01).
      CONCLUSIONS: Up-regulation of Ngb expression in brain injury induced by LPS is
      correlated with duration after challenge of LPS.

PMID- 19842563
TI  - Multimodality imaging of common and uncommon cystic focal liver lesions.
AB  - Cystic lesions of the liver are frequently encountered in clinical practice. In
      general, they can be classified as developmental, neoplastic, infectious,
      inflammatory, or miscellaneous lesions. Most cystic focal liver lesions have
      specific sonographic, computed tomographic, and magnetic resonance imaging
      features. These features help narrow, in combination with critical clinical
      information, the differential diagnosis and negate the need for biopsy or further
      diagnostic investigations in many patients. The purposes of this essay are to
      illustrate the characteristic sonographic, computed tomographic, and magnetic
      resonance imaging appearances of a gamut of both common and uncommon cystic focal
      liver lesions, to correlate these imaging findings with gross and microscopic
      pathology features, and to emphasize the essential information that allows
      differentiating among cystic hepatic lesions. Among others, imaging features that
      are important to recognize include the size and shape of the cyst; the presence
      and thickness of a cyst wall; the presence of calcifications, mural nodularity,
      debris, and septations; the density and signal intensity spectrum along with the
      enhancement pattern; the presence of communication with the biliary tree; and the
      presence of pericystic changes in the hepatic parenchyma. Familiarity with the
      complete spectrum of cystic focal liver lesions and a thorough understanding of
      their classic imaging appearances will undoubtedly allow a more definitive
      diagnosis and shorten the diagnostic workup.

PMID- 19842564
TI  - Hypervascular liver lesions.
AB  - Hypervascular hepatocellular lesions include both benign and malignant
      etiologies. In the benign category, focal nodular hyperplasia and adenoma are
      typically hypervascular. In addition, some regenerative nodules in cirrhosis may
      be hypervascular. Malignant hypervascular primary hepatocellular lesions include
      hepatocellular carcinoma, fibrolamellar carcinoma, and peripheral
      cholangiocarcinoma. Vascular liver lesions often appear hypervascular because
      they tend to follow the enhancement of the blood pool; these include hemangiomas,
      arteriovenous malformations, angiosarcomas, and peliosis. While most
      gastrointestinal malignancies that metastasize to the liver will appear
      hypovascular on arterial and portal-venous phase imaging, certain cancers such as
      metastatic neuroendocrine tumors (including pancreatic neuroendocrine tumors,
      carcinoid, and gastrointestinal stromal tumors) tend to produce hypervascular
      metastases due to the greater recruitment of arterial blood supply. Finally, rare
      hepatic lesions such as glomus tumor and inflammatory pseudotumor may have a
      hypervascular appearance.

PMID- 19842565
TI  - Understanding transient hepatic attenuation differences.
AB  - Transient hepatic attenuation differences (THADs) are the imaging manifestation
      of regional variations in the balance between hepatic arterial, portal venous,
      and third inflow sources of hepatic blood flow. THADs are typically wedge-shaped
      hypervascular regions visible on the hepatic arterial phase, and fade to isodense
      on venous and delayed phases. They are commonly seen in the setting of locally
      diminished portal venous inflow. Familiarity with the characteristic appearance
      and the physiology of THADs should permit discrimination of these fascinating
      pseudolesions from true space occupying masses.

PMID- 19842566
TI  - Liver masses with central or eccentric scar.
AB  - Central or eccentric scar has been described in (most frequently) focal nodular
      hyperplasia (FNH), large hemangioma, and fibrolamellar hepatocellular carcinoma,
      and moreover, a central scar may be rarely seen in conventional nonfibrolamellar
      hepatocellular carcinoma, (peripheral type) cholangiocarcinoma, and some hepatic
      metastases. Among the liver tumors with central or eccentric scar,
      differentiating FNH from other solid hepatic tumors is important because FNH
      usually requires no treatment. Multiphasic computed tomography and magnetic
      resonance imaging are useful for the differential diagnosis of liver tumors with
      central or eccentric scar. Liver-specific magnetic resonance contrast media will
      improve the differentiation between FNH and other solid hepatic tumors.

PMID- 19842567
TI  - Liver lesions with hepatic capsular retraction.
AB  - Retraction of the liver capsule may be associated with a diverse spectrum of
      benign and malignant etiologies. The more common causes include focal confluent
      fibrosis in cirrhotic livers, cholangiocarcinoma, and treated liver tumors, such
      as hepatocellular carcinoma, metastases, and lymphoma. Less common etiologies
      include primary sclerosing cholangitis, epithelioid hemangioendothelioma, hepatic
      hemangioma, solitary fibrous tumor of the liver, and hepatic inflammatory
      pseudotumor. Hepatic capsular retraction may also result from iatrogenic and
      noniatrogenic trauma. Due to the diversity and different nature of the various
      etiologies associated with this sign, it is important that radiologists be
      familiar with the characteristic features of these abnormalities, to avoid
      misdiagnosis that may adversely affect the therapeutic approach. It is also
      important to know that, contrary to some reports, hepatic capsular retraction is
      not a sign of malignant disease. The purpose of this article is to familiarize
      readers with the spectrum of benign and malignant etiologies of this sign and to
      point out additional computed tomographic findings that may allow confident
      diagnosis of the specific hepatic lesion responsible for the capsular retraction.
      The hepatic capsular and subcapsular regions may be affected by focal or diffuse
      pathologies affecting the liver. This hepatic area is more prone to be involved
      in various malignant and benign diseases due to several factors: the negative
      subdiaphragmatic pressure that may draw infected material and malignant cells
      toward the diaphragm, the perihepatic ligaments connecting the liver capsule with
      adjacent viscera, forming a direct root of dissemination, and the systemic blood
      inflow that supplies this region in addition to the portal and hepatic arterial
      blood flow. This is the reason for the multiple pathologic conditions and
      pseudolesions that occur at the hepatic capsular and subcapsular regions.

PMID- 19842568
TI  - Focal liver lesions hyperintense on T1-weighted magnetic resonance images.
AB  - This article reviews focal liver lesions hyperintense on T1-weighted magnetic
      resonance (MR) images and describes the underlying etiologies associated with
      their T1 signal intensity. Although focal liver lesions are commonly detected
      because of their iso- or hypointensity on T1-weighted images, lesions (benign or
      malignant) may present with T1 hyperintensity when they contain T1 shortening
      elements--such as fat, hemorrhage, copper, melanin, and highly concentrated
      proteins. Our discussion includes the description of state-of-the-art T1-weighted
      MR sequences and the imaging features of lesions on pre- and postcontrast MR
      images that are characteristic for lesion composition and useful for making
      accurate diagnosis.

PMID- 19842569
TI  - A sense of insecurity.

PMID- 19842570
TI  - "Harpist's finger: case report of a trauma-induced blister in a beginner harpist
      and review of string instrument-assocaited skin problems in musicians".

PMID- 19842571
TI  - Fungal foes: Rhinosporidium seeberi.

PMID- 19842572
TI  - Tinea cruris in children.
AB  - Tinea cruris is an intensely pruritic fungal infection of the groin and adjacent
      skin. Also known as crotch rot and jock itch, it can be a troubling important
      entity that at times is a clinical, diagnostic, and therapeutic challenge.
      Predisposing factors include heat, humidity, and hyperhidrosis, common
      accompaniments of high school-aged athletes. Furthermore, obesity and diabetes
      mellitus, additional risk factors for tinea cruris, are reaching unprecedented
      levels in adolescents. Treatment options range from improving hygiene to topical
      antifungal agents and systemic antifungal agents, the latter with potentially
      dangerous side effects.

PMID- 19842573
TI  - Skin biopsies to assess response to systemic corticosteroid therapy in early
      stage TEN: case report and review of the literature.
AB  - Toxic epidermal necrolysis (TEN) is a severe, mucocutaneous, necrolytic reaction
      to a variety of antigenic stimuli. The use of systemic corticosteroids in the
      treatment of TEN is controversial because of a lack of randomized, controlled,
      prospective studies, and because the effects of steroid therapy vary depending on
      the dosage and time of its administration during the course of TEN. Immediate
      intervention is crucial, and the response to corticosteroids in early-stage TEN
      can be difficult to clinically assess. In this report, we describe the use of
      serial skin biopsies to determine the efficacy of high-dose corticosteroids in
      patients with early-stage TEN. We present the case of a woman who was started on
      antiepileptic therapy with phenytoin sodium and developed TEN shortly thereafter.
      She was treated with intravenous methylprednisolone acetate for 1 week. The
      progression of the skin eruption was halted and the patient's condition began to
      stabilize. Skin biopsy specimens taken before and after steroid therapy revealed
      substantial improvement of the lymphocytic infiltrate and arrested epidermal
      necrosis. Serial skin biopsies in patients with early-stage TEN are helpful in
      assessing the initial response to corticosteroids and thus guide further therapy.

PMID- 19842574
TI  - Pili torti: clinical findings, associated disorders, and new insights into
      mechanisms of hair twisting.
AB  - Pili torti is a hair shaft disorder characterized by hair that does not grow long
      and is easily broken; the hair often has a coarse or spangled appearance. A
      diagnosis is made by light microscopy of flattened hair twisted 1800 along its
      axis. Although pili torti may be isolated, it is commonly associated with other
      congenital defects and therefore, if identified, further evaluation for possible
      neurologic deficits and ectodermal disorders is an important part of the clinical
      evaluation. Alterations of the inner root sheath likely lead to the abnormal
      molding and twisting of the hair shaft. More recent research suggests that these
      alterations may occur in the face of mitochondrial dysfunction and may be
      influenced by the presence of reactive oxygen species.

PMID- 19842575
TI  - In-transit metastasis from melanoma presenting as lymphangiectasis: a case
      report.
AB  - Malignant melanoma as a cause of inflammatory metastasis to the skin is a rare
      phenomenon referred to as in-transit metastasis (ITM). We report an unusual case
      of a patient who developed left leg lesions resembling lymphangiectasis. Punch
      biopsy results revealed atypical cells consistent with melanoma. The patient had
      a history of high-risk melanoma involving the left side of the lower extremity.
      This case highlights the need for a high index of suspicion for ITM in patients
      with a history of melanoma. Therapeutic options are discussed.

PMID- 19842576
TI  - Serum interferon-gamma is a psoriasis severity and prognostic marker.
AB  - The aim of this study was to measure serum interferon-gamma (IFN-gamma) levels in
      participants with different types and severities of psoriasis. The study was
      conducted on 21 participants with psoriasis. Participants were divided into 3
      groups according to disease severity: erythrodermic, severe plaque, and mild to
      moderate plaque psoriasis. Fifteen participants received different treatment
      modalities for 16 weeks and were followed for an additional 12 weeks. The enzyme
      linked immunosorbent assay technique was used to measure serum IFN-gamma levels
      in participants before treatment and compared with matched controls and
      participants receiving treatment. Significant differences were detected between
      participants and controls in mean serum IFN-gamma levels before treatment
      (P<.05). There was a positive correlation between serum IFN-gamma levels and
      psoriasis area and severity index (PASI) scores, and between serum IFN-gamm
      levels and clinical type of psoriasis, with the highest serum IFN-gamma levels in
      the erythrodermic psoriasis group and the lowest in the mild to moderate plaque
      psoriasis group. Irrespective of the type of treatment, 13 of 15 participants who
      showed improvement in disease condition with a significant decrease in PASI
      scores also had a significant decrease in serum IFN-gamma levels (P < .05).
      Moreover, participants with serum IFN-gamma levels that did not dramatically
      decrease had a shorter remission period compared with those who showed a
      significant decrease in serum IFN-gamma levels. The substantial elevation and
      variation in serum IFN-gamma levels according to disease severity suggest that
      IFN-gamma has a role in determining disease severity and therapy evaluation,
      which encourages further research on anti-IFN-gamma biologic therapy in the
      treatment of psoriasis.

PMID- 19842578
TI  - About palliative care.

PMID- 19842577
TI  - Optimizing management of actinic keratosis and photodamaged skin: utilizing a
      stepwise approach.
AB  - The incidence of photodamaged skin and skin lesions of all degrees of severity,
      from actinic keratosis (AK) to skin cancers, has dramatically increased. Actinic
      keratoses are pathologic, reflecting damage of essential skin cell functions and
      potentially progressing to invasive squamous cell carcinoma (SCC). The rate of
      progression is uncertain but may be as high as 10%. Because it is impossible to
      predict which AKs will progress to SCC, all lesions should be treated. Options
      include topical therapies, cryotherapy, curettage, and photodynamic therapy.
      Unfortunately, many individuals do not seek treatment or avoid it because of
      irritation, discomfort, and concern for scarring. Combining field-directed
      therapy and cryotherapy has been more effective than cryotherapy alone.
      Incorporating patient education with treatment may optimize outcomes. We propose
      a comprehensive 5-step approach for managing AK lesions and photodamaged skin
      that includes periodic clinical skin examinations; treating AK lesions with a
      combination of field- and lesion-directed therapy; and patient education
      regarding sun-protective measures and regular skin self-examinations.

PMID- 19842579
TI  - [Experiences of learning about nursing care].
AB  - The objective of this qualitative-exploratory was to learn about the process of
      developing knowledge in nursing care in terms of the experiences of the students
      who attend the seventh semester of a Nursing Course located in the State of Rio
      Grande do Sul, Brazil, from April to June/2007. Data collection was performed
      using the focal group technique and the information was analyzed using the
      thematic content analysis, which revealed one theme with three categories:
      Reflecting upon nursing education: the nurse's view: the knowledge of the
      profession; the process of education: learning about nursing care; and
      Expectations regarding the end of the course. The results showed that the care
      theme permeated the students' experiences, both implicitly and explicitly,
      although without a consistent philosophical and theoretical background.

PMID- 19842580
TI  - [Educational technology: assessment of a nursing personnel delegation website].
AB  - The use of information technology is a current reality in all fields of human
      knowledge. Technological incorporation has taken place in healthcare services,
      teaching institutions, as well as in the nurse's various work processes. This
      study aimed at evaluating a website developed perform a Nursing Personnel
      Delegation Plan, a quite relevant tool in healthcare human resources management.
      The methodology involved quantitative research with faculty members in the field
      of nursing administration and students from the eight public universities in Sao
      Paulo state offering Nursing programs. Among the major results, it was pointed
      out that 85% of the evaluators considered the website to be excellent or
      satisfactory. Comments sent by e-mail were also assessed; additionally, the
      website's authors performed a self-evaluation. The website was considered to be
      useful for both the professional practice (81.7% from excellent to satisfactory)
      and teaching (84.6% from excellent to satisfactory).

PMID- 19842581
TI  - [Technical nursing course at PROFAE-Ceara: an analysis from the graduates'
      perspective].
AB  - This study aimed to analyze PROFAE's technical Nursing course from the
      perspective of the students that had completed the course regarding the
      identification of strengths and weaknesses they identified during the program.
      This exploratory, qualitative-based descriptive study was carried out with
      graduates of the Public Healthcare School of Ceara, who had completed the course.
      Two focal groups composed of 21 graduates were organized in the months of May and
      June 2007. The content analysis was used forthe comprehension of the discourses.
      Results indicated that the course provided the graduates with a great deal of
      knowledge, thus positively affecting their lives and transforming them into
      agents of change in their work contexts. The study analyzed the curriculum, the
      methodology, the textbooks and other available materials, as well as the
      professors. The reported weaknesses were training field limitations, the length
      of the course, and the sponsorship management. The present assessment represents
      an important tool for the development of the course, generating an opportunity
      for the improvement of the proposal.

PMID- 19842582
TI  - [The experience of clinical nurses with nursing students: a phenomenological
      analysis].
AB  - This study aimed at understanding the reality of being a clinical nurse who works
      with nursing students while they develop their care experience in the clinical
      practice. The research was carried out by means of a phenomenological approach.
      Nine clinical nurses were interviewed and based on their discourses four
      categories of concretely experienced events were identified and interpreted
      according to Martin Heidegger's philosophical reference. Among the categories
      emerging from those discourses, this article highlights the following: being a
      nurse with students in their educational process, and the possibility of being
      with private and public university students. These aspects are presented here in
      order to encourage reflections on the important participation of clinical nurses
      in the education of future nursing professionals.

PMID- 19842583
TI  - [Insertion of USP nursing graduates into the job market: facilities and
      difficulties].
AB  - This descriptive, quantitative-based exploratory study was carried out between
      2000 and 2005 and aimed at characterizing the profile of students who had
      completed the Nursing Course at the University of Sao Paulo. From the 465
      graduates found in the period of the research, 175 (37.6%) provided responses for
      the data collection instrument. Their insertion in the job market occurred most
      of all into private hospitals by means of election processes in the city of Sao
      Paulo. The majority of the subjects remained in their first jobs from one to six
      months. The wage of the major part of the graduates ranged from US$ 950.50 to US$
      1520.00. In the data collection process, most of the researched participants had
      a formal job in private healthcare institutions, with average salaries of US$
      1437.50. Results showed that there was a quick insertion of the graduates into
      the job market.

PMID- 19842584
TI  - [Teaching-learning strategies in nursing--analysis using the Glasgow Coma Scale].
AB  - Using the Glasgow Coma Scale (ECGI) as a subject, this paper aims to analyze and
      verify the apprehension of knowledge towards the teaching-learning and self
      learning offered to nursing workers, and to check the degree of knowledge
      acquired during the process and possible results stemming from the nursing
      student/nursing worker association. This descriptive, quantitative-based study
      counted on the participation of 62 currently enrolled students in the first
      semester of the 4th year of nursing. The following teaching-learning strategies
      were used: expositive classes with the use of slides and videotape, and a basic
      text. Among participants, 41.9% were nursing workers; 61.3% informed to have
      taken care of patients with high alteration of the consciousness level,
      predominantly located in their working group. Statistically, there has been a
      successful improvement in the percentage of correct actions after the expositive
      class and videotape. Self-learning results showed no alteration either.
      Intergroup correlations displayed no disparity in the degree of acquired
      knowledge.

PMID- 19842585
TI  - [Knowledge of STD/AIDS among adolescent students].
AB  - This study aims to analyze the degree of knowledge adolescents have on STD/AIDS
      prevention, transmission, signs, and symptoms, and to contribute with the
      elaboration of educational actions in the University Extension Program called
      Corporality and Health Promotion. The research counted on 1,087 adolescents (40%
      females, 60% males) and was carried out in three elementary and high schools
      located in the municipality of Embu. A structured, multiple choice questionnaire
      was applied. Data indicated the achievement of the following results: as per the
      prevention, 92% of girls and 78% of boys referred to the use of condoms, while
      42% of girls and 43% of boys affirmed to wash their genitalia after the sexual
      relation; 75% females and 52% males quoted television as their source of
      information. As per the knowledge of STD, girls and boys indicated not to have
      much information on the issue. Regarding STD healing programs, 57% females and
      71% males affirmed not to have any knowledge on the issue; 5% of girls and 6% of
      boys thought AIDS to be curable. In a general perspective, we can conclude that
      girls were more familiar with the study's issues than boys.

PMID- 19842586
TI  - [Therapeutic factors in a group of people with diabetes].
AB  - The objective of the present research was to analyze the therapeutic factors
      identified in the accounts of the participants of a group of people with
      diabetes. An exploratory, assessing research carried out by means of semi
      structured interviews pinpointed the following therapeutic factors: information
      availability (100%); cohesion (100%); universality (86%); interpersonal learning
      (57%); development of socialization techniques (57%); altruism (28.5%); imitative
      behavior (28.5%); and hope stimulus (28.5%). The implementation of group
      intervention actions for the promotion of self-care towards diabetes carriers can
      generate a beneficial interaction among group members, thus allowing for
      experience exchange processes, as well as a broader understanding of the disease
      and other positive experiences evidenced by the presence of the therapeutic
      factors.

PMID- 19842587
TI  - [Relatives of patients with mental disorders: experiencing care at a psychosocial
      care center].
AB  - This study aimed at learning how relatives of patients with mental disorders have
      experienced dealing with a mental health care service. The exploratory and
      descriptive method was used with a qualitative approach. Data collection was
      performed using semi-structured interviews. Subjects were six family members who
      had been living for over three years with the process of having a mentally ill
      relative. Data analysis allowed us to infer that relatives who closely follow the
      patient had to deal with the knowledge acquired from their day-today experience
      and were subject to rejection by other family and community members. As regards
      the psychosocial care center, the relatives felt welcomed in their complaints,
      receiving a unique treatment; however, they did not knowthe mechanisms for social
      participation, which points to a deficiency in the service as it should stimulate
      forms of insertion into the community and the strengthening of the patients'
      rights as citizens.

PMID- 19842588
TI  - [A new sense for living: a comprehensive study about the adaptation process
      following spinal cord injuries].
AB  - The present study exploresanddescribesthe adaptation phenomena following spinal
      cord injury, focusing on the applied strategies of adaptation and identifying the
      necessary nursing care. The research used a qualitative approach, applying the
      Grounded Theory as a methodological reference. A group of nine individuals who
      had spinal cord injuries, and who presented a successful adaptation to a new way
      of life, was assessed by means of semi-directed interviews. Documentary analyses
      about life histories were performed and the Grounded Theory was used for data
      analyses. The study allowed for the explanation of the adaptation phenomena
      following the event of the spinal cord injury, which highlighted the influence of
      the acceptance of a new meaning of life and the maintenance of the will to manage
      new situations and challenges stemming from the injury. The central subject of
      this study is the spiritual dimension of the Individual. This anticipates a
      specific nursing intervention for people suffering from spinal cord injuries.

PMID- 19842589
TI  - [Quality of life evaluation in cancer patients to submitted to chemotherapy].
AB  - This descriptive and cross-sectional study aimed to assess the Quality of Life
      (QoL) of cancer patients who were receiving chemotherapy. The instrument European
      Organization for Research and Treatment of Cancer--Quality of Life Questionnaire
      Core-30 (EORTC QLQ-C30) was used for data collection. The sample consisted of 30
      patients who signed the informed consent term. Data were analyzed in SPSS
      software. The QLQ-C30 showed that, for physical, cognitive and social functions,
      and role performance mean scores ranged from 71.26 to 75.12, demonstrating a
      satisfactory level. In the emotional function, the mean score was low (55.46). On
      the symptoms scales, there were a predominance of insomnia, with a mean score of
      34.44, followed by pain 23.33 and fatigue 22.31. The QoL was satisfactory in all
      domains except for the emotional function, which scored low demonstrating that
      the collateral effects of chemotherapy exert a negative influence on patients'
      quality of life.

PMID- 19842590
TI  - [Heart transplantation: the experience of patients with Chagas disease].
AB  - Successful heart transplantation in patients with Chagas disease depends on
      special care to be provided during all phases of the transplantation process, and
      requires specific and rigorous follow-up by the health care team. Recipients must
      be aware of the permanence of the trypanosome in their organisms as well as of
      the possibility of infection reactivation after transplantation. Therefore, the
      patient's knowledge regarding this condition and his active participation in his
      own treatment are of utmost importance. This study aimed at investigating heart
      transplantation as experienced by patients with Chagas disease, seeking to
      understand the meanings that they attribute to such an experience. The
      methodological procedures included: patient selection; interviews; data analysis,
      indication of the meaning units and individual analysis; search for discourse
      convergence; and hermeneutic analysis of convergences. From the data analysis,
      the following themes emerged: the time lived by recipients with Chagas Disease;
      the conception of heart transplantation presented by patients with Chagas
      Disease; and care in the course of heart transplantation.

PMID- 19842591
TI  - [Hair removal repercussions on patient's self-esteem in craniotomy].
AB  - This quantitative-based, prospective-oriented study aims to evaluate the
      repercussion of hair removal in post-craniotomy's patient self-esteem. Data show
      that the majority of patients mentioned not having an altered self-esteem due to
      hair removal; self-esteem was kept the same among patients that were instructed
      about the hair removal process. The major part of patients made use of
      accessories as a strategy to hide shaved areas and believed that hair removal
      damaged neither their quality of life nor their social relationships. We conclude
      that the feelings directly related to the decrease of self-esteem are loss of
      physical attraction, insecurity and shame. The employment of accessories is made
      necessary towards improving self-esteem, and healthcare professionals must work
      with the psychosocial aspects of pre and post-surgery patients.

PMID- 19842592
TI  - [Profile of elderly patients who suffered trauma in Londrina--Parana].
AB  - The objective of this study is to characterize elderly victims of traumas
      admitted to three tertiary hospitals in Londrina, Paran State. This quantitative
      based research lasted six months and was carried out by means of an observational
      and cross-sectional study of 121 elderly people (60 to 74 years old) and their
      caregivers at the patients' homes, by the use of interviews. Results indicated
      that the majority of the elderly patients were males, with average age of 67.7
      years. The suffered traumas were distributed as follows: 62.0% by falls; 25.6% by
      transport accidents; and 10.4% by other sources. As a consequence of the trauma,
      the elderly patient had from one to three injuries and 11 (9.1%) died. Falls were
      the major source of traumas. This event can be avoided by the observations of
      predisposing intrinsic and extrinsic factors, aiming at establishing prevention
      strategies to this type of trauma.

PMID- 19842593
TI  - [Profile of the caregiver of dependent elderly family members in a home
      environment in the city of Porto, Portugal].
AB  - This descriptive research aims to identify the profile of the family caregiver
      using the World Health Organization's QPFC and WHOQOL-Bref (instrument
      application methods) in a sample of 120 family caregivers of dependent elderly
      patients who represented the population of three Healthcare Centers in the area
      of the Great Porto, Portugal. Data were collected in the period between January
      2005 and March 2005. Results indicated that female caregivers with 55 years of
      average age, who had other family care giving duties besides caring for the
      elderly family member, were the majority. The circumstances surrounding care
      giving, in the perspective of the elderly patient and the other family demands,
      generated negative consequences to the caregiver's life and health. However, at
      the same time, caregivers expressed positive perceptions and rewarding feelings
      when caring for the elderly family member. In a nutshell, it is essential for
      nurses to consider the binomial caregiver and dependent elderly patient, since
      both demand special healthcare attention from healthcare services.

PMID- 19842594
TI  - [From practice contexts towards the (co)construction of family nursing care
      models].
AB  - As nurses face challenges in the development of care focused on the family as a
      context and unit of intervention, this research aimed to identify family
      intervention processes in the context of Primary Healthcare. This qualitative
      based study adopted the investigation-action approach on a study plan's five-step
      path. By means of the comparative analysis of family care practices and
      conceptual models, the diagnosis results brought forth the need for change
      triggered by training processes. Having the Systemic Model, the Calgary Family
      Assessment Model, and the Calgary Family Intervention Model as references, the
      family nursing care model was (re)constructed and operationalized through the
      definition of attention and intervention areas. The (re) construction of the
      model from the needs identified by nurses and legitimated by their decision
      making processes is the basis for family nursing focused discussions.

PMID- 19842595
TI  - [Dimension of nursing and family care to hospitalized children: conceptions of
      nursing].
AB  - Family participation in the care of a hospitalized child, both regarding its
      forms and dimension, has been a theme of study in nursing. The objective of this
      study was to analyze the organization of both nursing care and family care to the
      hospitalized child. This qualitative research was performed using semi-structured
      interviews with nursing staff of a school-hospital. Theme analysis was used to
      guide data organization. The results show that nursing care focuses on
      procedures. Interaction with the children and their family is tangential to the
      caring process. Families have shared responsibilities with the staff but have not
      been recognized as a co-participant or been included into the caring perspective.
      Efforts should be made to create bonds to promote a logic regarding the process
      of work within the integrality perspective and to rescue the caring dimension of
      nursing.

PMID- 19842596
TI  - [The family's perception of its presence at the pediatric and neonatal intensive
      care unit].
AB  - This qualitative-based study aimed to understand how families perceive their own
      presence at the Pediatric and Neonatal Intensive Care Unit, as well as the
      acceptance of their presence by healthcare workers. Data was collected through
      semi-structured interviews with 14 parents of children admitted to the pediatric
      and neonatal ICU at two hospitals in northwestern Parana State, Brazil. Content
      analysis was chosen to interpret the data. The results revealed the suffering
      experienced by parents, the alteration of family dynamics resulting from the
      child's hospitalization, and the perception of the benefits of remaining close to
      the child in terms of welcoming and quality of care. It was concluded that
      parents value the professionals' respect and attention towards the child, thus
      creating bonds of affection, trust and gratitude for the care received.

PMID- 19842597
TI  - [Existential experience of mothers of hospitalized children in intensive
      pediatric care unit].
AB  - This study has the objective of understanding the existential experience of
      mothers of children hospitalized in an intensive pediatric care unit (IPCU). It
      is a qualitative-based research grounded on the humanistic nursing theory. The
      investigation scenario was the IPCU of a public hospital. Five mothers of
      children who were hospitalized in the referred unit participated in the
      investigation. Data were analyzed from the standpoint of the five phases of the
      phenomenological nursing. The following issues emerged from the collected
      statements: the relationship between mothers and nursing professionals at the
      moment of admission and throughout the child's hospitalization period in the
      IPCU; and mothers who experience fear, despair and loneliness in face of the
      child's disease. The present study highlights the complexity of a mother-centered
      approach and subsidizes a new look at the field of the care, teaching and nursing
      research.

PMID- 19842598
TI  - [Work process in the neonatal intensive care unit: building a holistic-oriented
      care].
AB  - This is a qualitative study aimed at analyzing the performance of healthcare
      professionals, as well as their contribution to a holistic-oriented care towards
      newborn babies in a Neonatal Intensive Care Unit (NICU). The study was carried
      out in the Sofia Feldman Hospital, in Belo Horizonte, State of Minas Gerais,
      Brazil. The study's subjects were ten healthcare professionals who cared for
      newborns in the NICU, and seven parents of admitted newborns. Data was collected
      by means of workshops and participant observation processes. Data were treated
      and analyzed by means of discourse analysis concepts. The resulting data
      highlighted the following aspects: the potential and holistic-oriented practices
      of healthcare professionals; the presence or absence of healthcare actions that
      materialized the holistic care; the different perceptions of the participants
      about the work carried out by the team; and in what sense the rationale of the
      work organization encompassed the workers' collective performance.

PMID- 19842599
TI  - [Phenomenological study about the nurse's home care for families of terminally
      ill patients].
AB  - The present study is a qualitative and phenomenological research aimed to
      understand the phenomenon Nurses working in the FHP (Family Health Program) and
      home care provided to the family living in a home where terminality of one of its
      members is being experienced. The study was carried out with healthcare providers
      who work in the Southeastern Region of the city of Sao Paulo/SP, Brazil.
      Existential phenomenology was used as the theoretical background. This study made
      possible the comprehension of what this experience meant to healthcare providers
      in a moment of being with the family in an existential situation of loss and
      death, creating a home protection network in order to make this process of
      terminality of one of the family members as smooth as possible. Even though
      permeated by care giving filled with humane feelings, thus representing a unique
      and remarkable experience, it was also a weary and difficult event that triggered
      labor health problems.

PMID- 19842600
TI  - [Vulnerability and prevention of sexual HIV transmission among HIV/AIDS
      serodiscordant couples].
AB  - This exploratory, descriptive study aimed to describe and analyze the
      vulnerability of HIV serodiscordant couples. The research was developed at an
      Aids Outpatient Service in a city in the State of Sao Paulo. Data were collected
      through individual interviews with 11 HIV/AIDS carriers who had a known
      serodiscordant partner. Prose analysis was applied for data organization and
      analyses, and the concept of vulnerability was used as a theoretical reference.
      The naturalization of HID/AIDS related to an undetectable viral load, the
      invulnerability feeling that stems from the time spent together by the couple,
      and its influence in the maintenance of safe sex are vulnerability factors for
      seronegative sexual partners. Specialized services to assist HIV/AIDS carriers
      need to include sexual partners in actions promoted by healthcare professionals
      targeting prevention and/or education.

PMID- 19842601
TI  - [Assessment of the work conditions in hospitals of Natal, Rio Grande do Norte
      State, Brazil].
AB  - This study identified how health professionals assess work conditions in
      different hospitals and verified how these conditions affect labor satisfaction.
      The sample was composed of 213 professionals from several healthcare fields. The
      analysis of the results indicated a distinct profile among the hospitals when it
      comes to work conditions. In a general perspective, the study observed low labor
      quality averages in State-run hospitals, while the highest ones were observed in
      the philanthropic hospital. This result corroborates the current condition of
      Brazilian public health. It also significantly associates labor satisfaction with
      the variables of family income and workplace. Therefore, conflicts in this
      scenario are considered as inevitable due to the precarious structure of some
      public health institutions; however, these problems can be foreseen and solved if
      hospitals create a free, accessible expression channel to all agents.

PMID- 19842602
TI  - [Occupational accidents due to exposure to biological material in the
      multidisciplinary team of the emergency service].
AB  - This transversal, survey-based research was carried out with a multiprofessional
      emergency care team in Belo Horizonte, between June and December 2006. The study
      aimed at estimating the incidence of occupational accidents by exposure to
      biological material, post-accidents conducts and demographic determinant factors.
      The study applied a structured questionnaire and descriptive analyses, as well as
      incidence calculations and logistic regression. The incidence of accidents with
      biological material reached 20.6%, being 40.8% by sharp materials and 49.0% by
      body fluids; 35.3% of the accidents took place among physicians and 24.0% among
      nurses. Post-accidents procedures: no medical assessment, 63.3%; under
      notification, 81.6%; no conduct, 55.0%; and no serological follow-up, 61.2%.
      Factors associated with accidents: working time in the institution (Odds Ratio-
      OR, 2.84; Credible Interval--CI 95%-1.22-6.62); working in advanced support units
      (OR = 4.18; CI 95%--1.64-10.64); and interaction between working time in the
      institution and working in Basic Support Unit (OR 0.27; CI 95%--0.07-1.00). In
      order to reduce accidents, the implementation of post-accident protocols and
      follow-up, as well as under-notification norms, are suggested.

PMID- 19842603
TI  - [Technology and humanization of the neonatal intensive care unit: reflections in
      the context of the health-illness process].
AB  - This article reflects on technology and humanization in care of newborns, having
      as theoretical premise the health-illness process. Some parallels are established
      among the several conceptions of health and illness, and their influences in the
      way we behave and think about the care spaces as subjects of the neonatal care.
      The Kangaroo Mother Care is presented as a relational technology that proposes to
      shelter the family-baby unity in the Neonatal Intensive Care Unit, valuing
      experiences and major needs of affection and comprehension.

PMID- 19842604
TI  - [Confusions and ambiguities in the classification of adverse events in the
      clinical research].
AB  - It is quite common to consider the terms ambiguous and confusing as synonyms.
      Confusing information brings together various data with similar meanings. In
      ambiguous information, on the other hand, several meanings are assigned to a
      single word. Excessive information also generates ambiguity; therefore, a
      concise, clear language is demanded. The term adverse event (AE) is defined as
      any inconvenient medical occurrence suffered by a subject during a clinical
      investigation research. Confusion and ambiguity in the use of words may generate
      relevant consequences in the appraisal of AEs. The objective of this present
      theoretical study is to harmonize the vocabulary applied in the characterization
      of risks and in the communication of AEs in clinical research processes. AEs may
      be classified according to their predictability, frequency, gravity, causality,
      and severity. Regulatory documents usually address AEs in their severity and
      causality aspects. Vocabulary conformity in the communication of AEs is an
      essential step towards avoiding inaccurate use of words with confused or
      ambiguous meanings.

PMID- 19842605
TI  - [Care, self-care and caring for yourself: a paradigmatic understanding thought
      for nursing care].
AB  - This article presents a reflection about care, self-care and caring for oneself
      and establishes these issues' relations with the paradigms of totality and
      simultaneity. On the first part of the text, care and its general aspects are
      contextualized; the second part discusses about care in Martin Heidegger's
      philosophical perspective; the third part explores self-care on Dorothea Orem's
      conception; the fourth part considers Michel Foucault's care of oneself. And
      finally, the fifth part aims to establish the relationship between the concepts
      of self-care and care of oneself, and the totality and simultaneity paradigms.
      Self-care and care of oneself are connected to the objectivism of the totality,
      and to the subjectivism of the simultaneity. These subjects lead nursing to
      comprehend such paradigmatic inheritance and its implications on the nursing
      care.

PMID- 19842606
TI  - The use of expert systems on the differential diagnosis of urinary incontinence.
AB  - The differential diagnosis of urinary incontinence classes is sometimes difficult
      to establish. As a rule, only the results of urodynamic testing allow an accurate
      diagnosis. However, this exam is not always feasible, because it requires special
      equipment, and also trained personnel to lead and interpret the exam. Some expert
      systems have been developed to assist health professionals in this field.
      Therefore, the aims of this paper are to present the definition of Artificial
      Intelligence; to explain what expert system and system for decision support are
      and its application in the field of health and to discuss some expert systems for
      differential diagnosis of urinary incontinence. It is concluded that expert
      systems may be useful not only for teaching purposes, but also as decision
      support in daily clinical practice. Despite this, for several reasons, health
      professionals usually hesitate to use the computer expert system to support their
      decision making process.

PMID- 19842607
TI  - [Stress and coping in perioperative period of breast cancer].
AB  - This study is a literature review with the objective to reflect about stress and
      coping in the perioperative period of breast cancer. The study was performed
      based on a national online database including studies published from 1996 to
      2006. The search found 63 articles, 17 of which were selected. The selected
      articles were read, analyzed and grouped into thematic categories: (1) Breast
      cancer as a stressor and impact on the diagnosis; (2) Stress and breast cancer
      treatment; (3) Coping and breast cancer; (4) The nurse as a cooperator in the
      coping process. This study found that national literature about breast cancer is
      substantial, but there few studies emphasize stress and cancer as a process lived
      by patients. Therefore, further studies should be performed regarding the
      stressors experienced by Brazilian women with breast cancer and the coping
      strategies they use.

PMID- 19842608
TI  - [The search for attitudinal commitment: tendency in the manager nurse's ethical
      behavior].
AB  - Historically, nurses' management functions have evidenced that their conduct is
      compatible with programmatic commitments. This fact was observed in the analysis
      of 18 studies carried out in healthcare services located in different Brazilian
      regions. Since the 1990's, management experts have alerted that traits such as
      commitment, interdisciplinarity, risk, uncertainty, spirituality, and ethical
      involvement will frame the characteristics of the human capital of 21st century
      organizations. In this much more humane environment, people's integrity and their
      way of relating at work must be based on the dimension of BEING. In order to face
      the new century institutions' healthcare demands, nurses are now urged to present
      a conduct permeated by the ethics of the attitudinal commitment. Thus, this study
      aims to stimulate a critical reflection on this ethical trend of nurses and
      finally propose that this trend be an essential value in nursing management
      processes.

PMID- 19842609
TI  - Prospective randomized trial of limbal relaxing incisions combined with
      microincision cataract surgery.
AB  - PURPOSE: To evaluate clinical outcomes of limbal relaxing incision (LRI) combined
      with bimanual phacoemulsification and insertion of an intraocular lens (IOL)
      developed for bimanual microincision cataract surgery (MICS). METHODS: In a
      prospective, single-center study, eyes with > or = 0.75 diopters (D) of
      keratometric astigmatism were randomly assigned to two surgical techniques: 1)
      bimanual MICS (non-LRI group) or 2) LRI combined with bimanual MICS (LRI group).
      Postoperative uncorrected distance visual acuity (UDVA), corrected distance
      visual acuity (CDVA), postoperative refractive error, corneal topography, and
      vector analysis of keratometric change between pre- and postoperative eyes were
      compared. RESULTS: In all cases of astigmatism in the LRI group, incisions for
      phacoemulsification and IOL insertion did not overlap or affect the LRIs.
      Uncorrected distance visual acuity was significantly higher in the LRI group
      (mean: 0.94) than in the non-LRI group (mean: 0.71, P = .009), although no
      difference was seen in CDVA in either group. Postoperative cylindrical error was
      significantly lower in the LRI group than in the non-LRI group (0.56 D and 1.51
      D, respectively, P = .0004). Cravy analysis showed that the vector change in
      cylinder was 1.44 D in the LRI group and 0.18 D in the non-LRI group (P = .0007).
      CONCLUSIONS: Limbal relaxing incision with bimanual MICS is an easy-to-follow
      combined surgery to correct preexisting astigmatism with predictable accuracy.

PMID- 19842610
TI  - Summary recommendations by the Advisory Committee on Immunization Practices
      (ACIP) for the use of H1N1 influenza vaccine for the 2009-2010 vaccination
      season.
AB  - This article summarizes current recommendations and the target populations to
      receive H1N1 vaccine once the vaccine supplies are released this fall.

PMID- 19842611
TI  - The roles of the occupational health nurse and infection control in managing a
      novel H1N1 surge--lessons from the front line.
AB  - The sudden appearance of the novel H1N1 influenza virus in North America
      highlights the importance of planning for such an event. Although the severity of
      this influenza is currently low, many lessons can be learned from the initial
      response by health care organizations.

PMID- 19842612
TI  - Evaluation of ceiling lifts in health care settings: patient outcome and
      perceptions.
AB  - Ceiling lifts have been introduced into health care settings to reduce manual
      patient lifting and thus occupational injuries. Although growing evidence
      supports the effectiveness of ceiling lifts, a paucity of research links
      indicators, such as quality of patient care or patient perceptions, to the use of
      these transfer devices. This study explored the relationship between ceiling lift
      coverage rates and measures of patient care quality (e.g., incidence of facility
      acquired pressure ulcers, falls, urinary infections, urinary incontinence, and
      assaults [patient to staff] in acute and long-term care facilities), as well as
      patient perceptions of satisfaction with care received while using ceiling lifts
      in a complex care facility. Qualitative semi-structured interviews were used to
      generate data. A significant inverse relationship was found between pressure
      ulcer rates and ceiling lift coverage; however, this effect was attenuated by
      year. No significant relationships existed between ceiling lift coverage and
      patient outcome indicators after adding the "year" variable to the model.
      Patients generally approved of the use of ceiling lifts and recognized many of
      the benefits. Ceiling lifts are not detrimental to the quality of care received
      by patients, and patients prefer being transferred by ceiling lifts. The
      relationship between ceiling lift coverage and pressure ulcer rates warrants
      further investigation.

PMID- 19842614
TI  - Occupational health nurses' roles, credentials, and continuing education in
      Ontario, Canada.
AB  - The role of the occupational health nurse is broad and includes health care
      provider, manager/coordinator, educator/advisor, and case manager and consultant,
      depending on the type of industry and the country in which the nurse practices.
      Regardless of the type of role, the occupational health nurse must participate in
      continuing nursing education (CNE) activities. This study describes the roles,
      credentials, and number of CNE activities undertaken by occupational health
      nurses working in Ontario, Canada. Using a nonexperimental descriptive design, a
      questionnaire was mailed to all practicing occupational health nurses who are
      members (n=900) of a local nursing association. Three hundred fifty-four
      questionnaires were returned. Nurses reported a variety of roles in the following
      categories: case management, health promotion, policy development, infection
      control/travel health, ergonomics, education, research, health and safety, direct
      care, consultation, disaster preparedness, and industrial hygiene. Sixty-five
      percent of nurses held an occupational health nurse credential, and 19% of nurses
      attended more than 100 hours of CNE annually. Occupational health nurses have
      multiple workplace roles. Many attend CNE activities and they often prepare for
      credentialing.

PMID- 19842615
TI  - Malaria.
AB  - For international business travelers, malaria is a serious and sometimes fatal
      vector-borne disease that is largely preventable with effective counseling and
      proper use of a prescribed antimalarial.

PMID- 19842616
TI  - Structure and photoinduced electron transfer in DNA hairpin conjugates possessing
      a tethered 5'-pyrenecarboxamide.
AB  - The structure, spectroscopy, and photophysical behavior of a series of hairpin
      forming conjugates possessing a 5'-tethered N-alkylpyrenecarboxamide chromophore
      have been investigated. Comparison of the NMR spectra of the conjugates and
      analogs lacking the tethered pyrene indicates that the pyrene does not behave as
      an end-capping group but rather is intercalated between the two terminal hairpin
      base pairs. An intercalated structure is also consistent with the thermodynamic
      parameters for hairpin formation and the steady state and transient spectral
      properties of the conjugates. Quenching of the pyrene fluorescence and transient
      absorption spectra is observed only when guanine is located in one of the two
      terminal base pairs and is attributed to hole injection from singlet pyrene to
      guanine. The fast component of the transient decay is more rapid when guanine is
      located in the second vs first base pair, consistent with an intercalated but not
      an end-capped geometry. Spectral broadening of ultraviolet, fluorescence, and
      transient absorption spectra is attributed to multiple ground state
      conformations.

PMID- 19842617
TI  - Multifrequency pulsed electron paramagnetic resonance on metalloproteins.
AB  - Metalloproteins often contain metal centers that are paramagnetic in some
      functional state of the protein; hence electron paramagnetic resonance (EPR)
      spectroscopy can be a powerful tool for studying protein structure and function.
      Dipolar spectroscopy allows the determination of the dipole-dipole interactions
      between metal centers in protein complexes, revealing the structural arrangement
      of different paramagnetic centers at distances of up to 8 nm. Hyperfine
      spectroscopy can be used to measure the interaction between an unpaired electron
      spin and nuclear spins within a distance of 0.8 nm; it therefore permits the
      characterization of the local structure of the paramagnetic center's ligand
      sphere with very high precision. In this Account, we review our laboratory's
      recent applications of both dipolar and hyperfine pulsed EPR methods to
      metalloproteins. We used pulsed dipolar relaxation methods to investigate the
      complex of cytochrome c and cytochrome c oxidase, a noncovalent protein-protein
      complex involved in mitochondrial electron-transfer reactions. Hyperfine sublevel
      correlation spectroscopy (HYSCORE) was used to study the ligand sphere of iron
      sulfur clusters in complex I of the mitochondrial respiratory chain and substrate
      binding to the molybdenum enzyme polysulfide reductase. These examples
      demonstrate the potential of the two techniques; however, they also highlight the
      difficulties of data interpretation when several paramagnetic species with
      overlapping spectra are present in the protein. In such cases, further approaches
      and data are very useful to enhance the information content. Relaxation filtered
      hyperfine spectroscopy (REFINE) can be used to separate the individual components
      of overlapping paramagnetic species on the basis of differences in their
      longitudinal relaxation rates; it is applicable to any kind of pulsed hyperfine
      or dipolar spectroscopy. Here, we show that the spectra of the iron-sulfur
      clusters in complex I can be separated by this method, allowing us to obtain
      hyperfine (and dipolar) information from the individual species. Furthermore,
      performing pulsed EPR experiments at different magnetic fields is another
      important tool to disentangle the spectral components in such complex systems.
      Despite the fact that high magnetic fields do not usually lead to better spectral
      separation for metal centers, they provide additional information about the
      relative orientation of different paramagnetic centers. Our high-field EPR
      studies on cytochrome c oxidase reveal essential information regarding the
      structural arrangement of the binuclear Cu(A) center with respect to both the
      manganese ion within the enzyme and the cytochrome in the protein-protein complex
      with cytochrome c.

PMID- 19842618
TI  - Isoform-selective inactivation of human arylamine N-acetyltransferases by
      reactive metabolites of carcinogenic arylamines.
AB  - Human arylamine N-acetyltransferases (NATs) are expressed as two polymorphic
      isoforms, NAT1 and NAT2, that have toxicologically significant functions in the
      detoxification of xenobiotic arylamines by N-acetylation and in the bioactivation
      of N-arylhydroxylamines by O-acetylation. NAT1 also catalyzes the N-acetylation
      of 4-aminobenzoylglutamic acid, a product of folic acid degradation, and is
      associated with endogenous functions in embryonic development. On the basis of
      earlier studies with hamster NAT1, hamster NAT2, and human NAT1, we proposed that
      human NAT2 would be more susceptible than NAT1 to inactivation by N
      arylhydroxamic acid metabolites of arylamines. Kinetic analyses of the
      inactivation of recombinant NAT1 and NAT2 by the N-arylhydroxamic acid, N-hydroxy
      2-acetylaminofluorene (N-OH-AAF), as well as the inactivation of NAT2 by N
      hydroxy-4-acetylaminobiphenyl (N-OH-4-AABP), resulted in second-order
      inactivation rate constants (k(inact)/K(I)) that were several fold greater for
      NAT2 than for NAT1. Mass spectrometric analysis showed that inactivation of NAT2
      in the presence of the N-arylhydroxamic acids was due to formation of a
      sulfinamide adduct with Cys68. Treatment of HeLa cells with N-OH-4-AABP and N-OH
      AAF revealed that the compounds were less potent inactivators of intracellular
      NAT activity than the corresponding nitrosoarenes, but unexpectedly, the
      hydroxamic acids caused a significantly greater loss of NAT1 activity than of
      NAT2 activity. Nitrosoarenes are the electrophilic products responsible for NAT
      inactivation upon interaction of the enzymes with N-arylhydroxamic acids, as well
      as being metabolic products of arylamine oxidation. Treatment of recombinant NAT2
      with the nitrosoarenes, 4-nitrosobiphenyl (4-NO-BP) and 2-nitrosofluorene (2-NO
      F), caused rapid and irreversible inactivation of the enzyme by sulfinamide
      adduct formation with Cys68, but the k(inact)/K(I) values for inactivation of
      recombinant NAT2 and NAT1 did not indicate significant selectivity for either
      isoform. Also, the IC(50) values for inactivation of HeLa cell cytosolic NAT1 and
      NAT2 by 4-NO-BP were similar, as were the IC(50) values obtained with 2-NO-F.
      Treatment of HeLa cells with low concentrations (1-10 microM) of either 4-NO-BP
      or 2-NO-F resulted in preferential and more rapid loss of NAT1 activity than NAT2
      activity. Because of its wide distribution in human tissues and its early
      expression in developing tissues, the apparent high sensitivity of intracellular
      NAT1 to inactivation by reactive metabolites of environmental arylamines may have
      important toxicological consequences.

PMID- 19842619
TI  - The chemical forms of mercury in aged and fresh dental amalgam surfaces.
AB  - Mercury-containing dental amalgam is known to be a source of human exposure to
      mercury. We have explored the use of electron yield Hg L(III) X-ray absorption
      spectroscopy to characterize the chemical nature of dental amalgam surfaces. We
      find that the method is practical and that it shows extensive mercury depletion
      in the surface of the aged amalgam with significant differences between old and
      fresh amalgam surfaces. Whereas the fresh amalgam gives spectra that are typical
      of metallic mercury, the aged amalgam is predominantly beta-mercuric sulfide. The
      toxicological implications of these results are discussed.

PMID- 19842620
TI  - Dependence of macroscopic wetting on nanoscopic surface textures.
AB  - The hydrophobicity of a surface can be enhanced by physical textures. However, no
      existing theories of surface wetting can provide guidance to pinpoint the texture
      size requirement to achieve super/ultrahydrophobicity. Here, we show that the
      three-phase contact line tension, tau, is an important link to understand the
      dependence of macroscopic wetting on physical texture size in an ideal Cassie
      regime. Specifically, we show that texture size is the dominant parameter in
      determining surface hydrophobicity when the size approaches a limiting physical
      length scale, as defined by tau and the surface tension of the liquid.

PMID- 19842621
TI  - Engineering phage materials with desired peptide display: rational design
      sustained through natural selection.
AB  - Genetic engineering of phage provides novel opportunities to build various
      nanomaterials by displaying functional peptide motifs on its surface coat
      protein. However, any genetic modifications of phage coat proteins must be able
      to accommodate their many biological roles in the phage replication process. To
      express functional but inherently unfavorable peptide motifs on major coat
      protein pVIII, we devised a novel genetic conjugation method to circumvent
      bacterial biological censorship. Constraining the designed peptides among the
      degenerate flanking residues, we obtained a pVIII library of phage that retained
      the desired sequences yet could navigate through the phage replication process
      due to the naturally selected flanking residues. Further, we systematically
      analyzed the biochemical and size-related compensation mechanisms of the pVIII
      expressed peptides by constructing four chemically diverse (His, Trp, Glu, Lys)
      partial library series. Described genetic conjugation methodology can serve to
      improve the design of engineered phage and allow further exploitation of these
      particles as functional nanobiomaterials for various applications.

PMID- 19842622
TI  - Extension arm facilitated pegylation of alphaalpha-hemoglobin with modifications
      targeted exclusively to amino groups: functional and structural advantages of
      free Cys-93(beta) in the PEG-Hb adduct.
AB  - Cys-93(beta) of hemoglobin (Hb) was reversibly protected as a mixed disulfide
      with thiopyridine during extension arm facilitated (EAF) PEGylation and its
      influence on the structural and functional properties of the EAF-PEG-Hb has been
      investigated. Avoiding PEGylation of Cys-93(beta) in the EAF-PEG-Hb lowers the
      level of perturbation of heme pocket, alpha1beta2 interface, autoxidation, heme
      loss, and the O(2) affinity, as compared to the EAF-PEG-Hb with PEGylation of Cys
      93(beta).The structural and functional advantages of reversible protection of Cys
      93(beta) during EAF PEGylation of oxy-Hb has been compared with Euro PEG-Hb
      generated by EAF PEGylation of deoxy Hb where Cys-93(beta) is free in the final
      product. The alphaalpha-fumaryl cross-linking and EAF PEGylation targeted
      exclusively to Lys residues has been combined together for generation of second
      generation EAF-PEG-Hb with lower oxygen affinity. The PEG chains engineered on
      Lys as well as PEGylation of Cys-93(beta) independently contribute to the
      stabilization of oxy conformation of Hb and hence increase the oxygen affinity of
      Hb. However, oxygen affinity of the EAF-PEG-alphaalpha-Hb is more sensitive to
      the presence of PEGylation on Cys-93(beta) than that of the EAF-PEG-Hb. The
      present modified EAF PEGylation platform is expected to facilitate the design of
      novel versions of the EAF-PEG-Hbs that can now integrate the advantages of
      avoiding PEGylation of Cys-93(beta).

PMID- 19842623
TI  - Monitoring of biological one-electron reduction by (19)F NMR using hypoxia
      selective activation of an (19)F-labeled indolequinone derivative.
AB  - Biological reduction of fluorine-labeled indolequinone derivative (IQ-F) was
      characterized by (19)F NMR for quantitative molecular understanding. The chemical
      shift change in (19)F NMR allowed monitoring of the enzymatic reduction of IQ-F.
      Upon hypoxic treatment of IQ-F with NADPH:cytochrome P450 reductase, IQ-F was
      activated via catalytic one-electron reduction to release nonafluoro-tert-butyl
      alcohol (F-OH), while the formation of F-OH was significantly suppressed under
      aerobic conditions. Similar hypoxia-selective reduction of IQ-F occurred within
      A549 cells, which expresses NADPH:cytochrome P450 reductase. The kinetic analysis
      was also performed to propose a reaction mechanism. The molecular oxygen slightly
      prevents the binding of IQ-F to reductase, while the rate of net reaction was
      decreased due to oxidation of a semiquinone anion radical intermediate generated
      by one-electron reduction of IQ-F. The disappearance of IQ-F and appearance of F
      OH were imaged by (19)F fast spin echo, thus visualizing the hypoxia-selective
      reduction of IQ-F by means of MR imaging.

PMID- 19842624
TI  - Multi-assay-based structure-activity relationship models: improving structure
      activity relationship models by incorporating activity information from related
      targets.
AB  - Structure-activity relationship (SAR) models are used to inform and to guide the
      iterative optimization of chemical leads, and they play a fundamental role in
      modern drug discovery. In this paper, we present a new class of methods for
      building SAR models, referred to as multi-assay based, that utilize activity
      information from different targets. These methods first identify a set of targets
      that are related to the target under consideration, and then they employ various
      machine learning techniques that utilize activity information from these targets
      in order to build the desired SAR model. We developed different methods for
      identifying the set of related targets, which take into account the primary
      sequence of the targets or the structure of their ligands, and we also developed
      different machine learning techniques that were derived by using principles of
      semi-supervised learning, multi-task learning, and classifier ensembles. The
      comprehensive evaluation of these methods shows that they lead to considerable
      improvements over the standard SAR models that are based only on the ligands of
      the target under consideration. On a set of 117 protein targets, obtained from
      PubChem, these multi-assay-based methods achieve a receiver-operating
      characteristic score that is, on the average, 7.0 -7.2% higher than that achieved
      by the standard SAR models. Moreover, on a set of targets belonging to six
      protein families, the multi-assay-based methods outperform chemogenomics-based
      approaches by 4.33%.

PMID- 19842625
TI  - Impact of nanoscale roughness of titanium thin film surfaces on bacterial
      retention.
AB  - Two human pathogenic bacteria, Staphylococcus aureus CIP 68.5 and Pseudomonas
      aeruginosa ATCC 9025, were adsorbed onto surfaces containing Ti thin films of
      varying thickness to determine the extent to which nanoscale surface roughness
      influences the extent of bacterial attachment. A magnetron sputter thin film
      system was used to deposit titanium films with thicknesses of 3, 12, and 150 nm
      on glass substrata with corresponding surface roughness parameters of R(q) 1.6,
      1.2, and 0.7 nm (on a 4 microm x 4 microm scanning area). The chemical
      composition, wettability, and surface architecture of titanium thin films were
      characterized using X-ray photoelectron spectroscopy, contact angle measurements,
      atomic force microscopy, three-dimensional interactive visualization, and
      statistical approximation of the topographic profiles. Investigation of the
      dynamic evolution of the Ti thin film topographic parameters indicated that three
      commonly used parameters, R(a), R(q), and R(max), were insufficient to
      effectively characterize the nanoscale rough/smooth surfaces. Two additional
      parameters, R(skw) and R(kur), which describe the statistical distributions of
      roughness character, were found to be useful for evaluating the surface
      architecture. Analysis of bacterial retention profiles indicated that bacteria
      responded differently to the surfaces on a scale of less than 1 nm change in the
      R(a) and R(q) Ti thin film surface roughness parameters by (i) an increased
      number of retained cells by a factor of 2-3, and (ii) an elevated level of
      secretion of extracellular polymeric substances.

PMID- 19842626
TI  - Heating and cooling dynamics of carbon nanotubes observed by temperature-jump
      spectroscopy and electron microscopy.
AB  - Microscopy imaging indicates that in situ carbon nanotubes (CNTs) irradiation
      with relatively low dosages of infrared radiation results in significant heating
      of the tubes to temperatures above 1300 K. Ultrafast temperature-jump experiments
      reveal that CNTs laser-induced heating and subsequent cooling in solution take
      tens and hundreds of picoseconds, respectively. Given the reported transient
      behavior, these observations suggest novel ways for a T-jump methodology,
      unhindered by the requirement for excitation of water in the study of biological
      structures. They also provide the rate information needed for optimization of
      photothermal therapy that invokes infrared irradiation to selectively heat and
      annihilate cancer cells.

PMID- 19842627
TI  - Water oxidation at a tetraruthenate core stabilized by polyoxometalate ligands:
      experimental and computational evidence to trace the competent intermediates.
AB  - Converging UV-vis, EPR, rRaman, and DFT calculations highlight the evolution of
      [Ru(4)(H(2)O)(4)(mu-O)(4)(mu-OH)(2)(gamma-SiW(10)O(36))(2)](10-), 1, to high
      valent intermediates. In analogy with the natural enzyme, five different
      oxidation states, generated from 1, have been found to power the catalytic cycle
      for water oxidation. A high electrophilic tetraruthenium(V)-hydroxo species is
      envisaged as the competent intermediate, undergoing nucleophilic attack by an
      external water molecule as a key step in the formation of a new O-O bond under
      catalytic conditions.

PMID- 19842628
TI  - Selective characterization of microsecond motions in proteins by NMR relaxation.
AB  - The three-dimensional structures of macromolecules fluctuate over a wide range of
      time-scales. Separating the individual dynamic processes according to frequency
      is of importance in relating protein motions to biological function and
      stability. We present here a general NMR method for the specific characterization
      of microsecond motions at backbone positions in proteins even in the presence of
      other dynamics such as large-amplitude nanosecond motions and millisecond
      chemical exchange processes. The method is based on measurement of relaxation
      rates of four bilinear coherences and relies on the ability of strong continuous
      radio frequency fields to quench millisecond chemical exchange. The utility of
      the methodology is demonstrated and validated through two specific examples
      focusing on the thermo-stable proteins, ubiquitin and protein L, where it is
      found that small-amplitude microsecond dynamics are more pervasive than
      previously thought. Specifically, these motions are localized to alpha helices,
      loop regions, and regions along the rim of beta sheets in both of the proteins
      examined. A third example focuses on a 28 kDa ternary complex of the chaperone
      Chz1 and the histones H2A.Z/H2B, where it is established that pervasive
      microsecond motions are localized to a region of the chaperone that is important
      for stabilizing the complex. It is further shown that these motions can be well
      separated from extensive millisecond dynamics that are also present and that
      derive from exchange of Chz1 between bound and free states. The methodology is
      straightforward to implement, and data recorded at only a single static magnetic
      field are required.

PMID- 19842629
TI  - Understanding membranes through the molecular design of lipids.
AB  - Lipids are amphiphilic molecules that are composed of hydrophilic and hydrophobic
      regions. A typical membranous aggregate (vesicles, water-filled lipid
      nanospheres) is formed upon the self-organization of lipids in water from a
      diverse collection of amphiphiles producing a dynamic supramolecular structure
      that shows phase behavior and ordering as required for specific biological
      functions. The determination of various physical properties of lipid aggregates
      is the key to determining structure-function relationships. Over the years, we
      have designed and synthesized a wide variety of lipid molecular systems for the
      investigation of their membrane-forming properties and have used them for
      purposes such as gene delivery and enzyme activation. In this feature article, we
      focus on our work on various types of lipids including ion-paired amphiphiles,
      cholesterol-based lipids, aromatic lipids, macrocyclic lipids containing
      disulfide tethers, cationic dimeric lipids, and so forth. The emphasis is on
      experimental design and bottom-line conclusions.

PMID- 19842630
TI  - Cysteine and pH-responsive hydrogel based on a saccharide derivative with an
      aldehyde group.
AB  - For the development of chemoresponsive hydrogel, a new saccharide-derived
      hydrogelator 1 [methyl-4,6-O-(4'-aldehydephenylidene)-alpha-D-glucopyranoside]
      was synthesized and characterized. The resulting hydrogel not only shows thermal
      responsiveness but also exhibits cysteine and pH responsiveness due to the
      presence of aldehyde and acetal groups in 1. The release of guest molecules from
      the hydrogel of 1 was examined by employing compound 2 (fluorescein disodium) and
      compound 3 [methyl-4,6-O-(2'-pyrenylidene)-alpha-D-glucopyranoside] as guest
      molecules. The results indicate that the release of compound 2 from the hydrogel
      of 1 is controlled by the diffusion process, while the release of compound 3 from
      the hydrogel of 1 is facilitated by the presence of cysteine. These results
      demonstrate (1) the proof of principle to design chemoresponsive gels by
      incorporating reactive groups into the gelators and (2) it is possible to
      stimulate the release of guest molecules from hydrogels upon addition of reactive
      chemicals by manipulating the intermolecular interactions among the hydrogelators
      and guest molecules.

PMID- 19842631
TI  - Self-guided one-sided metal reduction in te nanowires leading to Au-Te
      matchsticks.
AB  - Highly anisotropic nanoscale structures are fundamentally important for
      understanding the properties of hybrid nanoscale systems and self-organization
      phenomena, but they are typically difficult to prepare experimentally. Hybrid Au
      and Te matchstick-like nanostructures, which display high structural anisotropy,
      were synthesized using small Au clusters as seeds. The matchsticks were found to
      be an exclusive product of this reaction. We hypothesize that the mechanism of
      the synthesis is based on self-directed site-specific reduction of Au ions due to
      the gradually increasing dipole moment facilitating this process on one side of
      Te nanorods, which is supported by quantum mechanical calculations.

PMID- 19842632
TI  - Multifunctional superparamagnetic Janus particles.
AB  - In this study, we report the microfluidic-based synthesis of a multifunctional
      Janus hydrogel particle with anisotropic superparamagnetic properties and
      chemical composition for the bottom-up assembly of hydrogel superstructures. In a
      uniform magnetic field, the resulting Janus magnetic particles fabricated in the
      present method exhibit chainlike or meshlike superstructure forms, the complexity
      of which can be simply modulated by particle density and composition. This
      controllable field-driven assembly of the particles can be potentially used as
      building blocks to construct targeted superstructures for tissue engineering.
      More importantly, we demonstrated that this method also shows the ability to
      generate multifunctional Janus particles with great design flexibilities: (a)
      direct encapsulation and precise spatial distribution of biological substance and
      (b) selective surface functionalization in a particle. Although these
      monodisperse particles find immediate use in tissue engineering, their ability to
      self-assemble with tunable anisotropic configurations makes them an intriguing
      material for several exciting areas of research such as photonic crystals, novel
      microelectronic architecture, and sensing.

PMID- 19842633
TI  - Use of single particle aerosol mass spectrometry for the automated nondestructive
      identification of drugs in multicomponent samples.
AB  - In this work, single particle aerosol mass spectrometry (SPAMS) was used to
      identify the active drug ingredients in samples of multicomponent over-the
      counter (OTC) drug tablets with minimal damage to the tablets. OTC drug tablets
      in various formulations were analyzed including single active ingredient tablets
      and multi-ingredient tablets. Using a sampling apparatus developed in-house,
      micrometer-sized particles were simultaneously dislodged from tablets and
      introduced to the SPAMS, where dual-polarity mass spectra were obtained from
      individual particles. Active ingredients were identified from the parent ions and
      fragment ions formed from each sample, and alarm files were developed for each
      active ingredient, allowing successful automated identification of each compound
      in a mixture. The alarm algorithm developed for SPAMS correctly identified all
      drug compounds in all single-ingredient and multi-ingredient tablets studied. A
      further study demonstrated the ability of this technique to identify the active
      ingredient in a single tablet analyzed in the presence of several other
      nonidentical tablets. In situ measurements were also made by sampling directly
      from a drug sample in its original bottle. A single tablet embedded in 11
      identical tablets of different composition was detected in this manner. Overall,
      this work demonstrates the ability of the SPAMS technique to detect a target drug
      compound both in complex tablets, i.e., multidrug ingredient tablets, and complex
      sampling environments, i.e., multitablet sampling sources. The technique is
      practically nondestructive, leaving the characteristic shape, color, and imprint
      of a tablet intact for further analysis. Applications of this technique may
      include forensic and pharmaceutical analysis.

PMID- 19842634
TI  - Multistep approach for the structural identification of biotransformation
      products of iodinated X-ray contrast media by liquid chromatography/hybrid triple
      quadrupole linear ion trap mass spectrometry and (1)H and (13)C nuclear magnetic
      resonance.
AB  - This study investigated the application of a hybrid triple quadrupole linear ion
      trap mass spectrometer (Qq-LIT-MS) in combination with NMR to elucidate the
      chemical structures of 27 biotransformation products (TPs) of the nonionic
      iodinated X-ray contrast media (ICM), iohexol, iomeprol, and iopamidol, formed in
      contact with soil. The combination of MS(2) and MS(3) spectra with Qq-LIT-MS was
      essential to determine the MS fragmentation pathways crucial for structural
      elucidation. (1)H and (13)C NMR analyses were needed to confirm the chemical
      structures of TPs proposed by MS fragmentation. Biotransformation occurred
      exclusively at the side chains of the iodinated X-ray contrast media, while the
      iodinated benzene ring remained unaltered. Several of the newly identified TPs of
      the ICM were found in surface water, groundwater, and even drinking water.
      Concentrations as high as 1450 +/- 110 ng/L (iomeprol TP629) were detected in
      groundwater that is influenced by wastewater infiltration, and as high as 289 +/-
      41 ng/L (iomeprol TP643) in drinking water.

PMID- 19842635
TI  - Surface and bulk collapse transitions of thermoresponsive polymer brushes.
AB  - We elucidate the sequence of events occurring during the collapse transition of
      thermoresponsive copolymer brushes based on poly(di(ethyleneglycol) methyl ether
      methacrylate) chains (PMEO2MA) grown by atom-transfer radical polymerization
      (ATRP). The collapse of the bulk of the brush is followed by quartz crystal
      microbalance measurements with dissipation monitoring (QCM-D), and the collapse
      of its outer surface is assessed by measuring equilibrium water contact angles in
      the captive bubble configuration. The bulk of the brush collapses over a broad
      temperature interval (approximately 25 degrees C), and the end of this process is
      signaled by a sharp first-order transition of the surface of the brush. These
      observations support theoretical predictions regarding the occurrence of a
      vertical phase separation during collapse, with surface properties of
      thermoresponsive brushes exhibiting a sharp variation at a temperature of
      T(br)(surf). In contrast, the bulk properties of the brush vary smoothly, with a
      bulk transition T(br)(bulk) occurring on average approximately 8 degrees C below
      T(br)(surf) and approximately 5 degrees C below the lower critical solution
      temperature (LCST) of free chains in solution. These observations should also be
      valid for planar brushes of other neutral, water-soluble thermoresponsive
      polymers such as poly(N-isopropylacrylamide) (PNIPAM). We also propose a way to
      analyze more quantitatively the temperature dependence of the QCM-D response of
      thermoresponsive brushes and deliver a simple thermodynamic interpretation of
      equilibrium contact angles, which can be of use for other complex temperature
      responsive solvophilic systems.

PMID- 19842637
TI  - A universal strategy for development of a method for absolute quantification of
      therapeutic monoclonal antibodies in biological matrices using differential
      dimethyl labeling coupled with ultra performance liquid chromatography-tandem
      mass spectrometry.
AB  - Although the strategic use of enzymatic digestion combined with isotope dilution
      mass spectrometry has been increasingly developed and used for the absolute
      quantification of therapeutic and endogenous proteins in the biopharmaceutical
      industry over the past several years, the lack of an appropriate internal
      standard has become the rate-limiting step in the development of a standardized
      analytical approach to provide bioanalytical support for both preclinical and
      clinical studies. In this study, we present a universal strategy for fast
      development and validation (within 1-2 weeks) of a method for absolute
      quantification of a therapeutic monoclonal antibody in biological matrices using
      differential dimethyl labeling coupled with UPLC-MS/MS. Differential dimethyl
      labeling of tryptic peptides generated from the purified therapeutic monoclonal
      antibody and those derived from proteins in cynomolgus monkey serum with either
      d(2)- or d(0)-formaldehyde provided a fast, cost-effective, and standardized
      approach to generate internal standards for any surrogate peptides that are used
      to quantify the therapeutic monoclonal antibody in biological matrices. This
      labeling reaction employs inexpensive and commercially available reagents, d(0)-
      or d(2)-formaldehyde, to globally label the N-terminus and epsilon-amino group of
      Lys in a peptide via reductive amination. Moreover, the process is simple,
      relatively fast (<2 h reaction time), specific, and quantitative under mild
      reaction conditions. The chromatographic run time is 6 min per sample. The
      linearity of the assay for the selected monoclonal antibody was established from
      1.00 to 1000 mug/mL with accuracy and precision within 15% at all concentrations.
      The intraday and interday assay accuracy (%RE) and coefficient of variations
      (CV%) are all within 15% for all QCs (2.00, 4.00, 20.0, 100, 750 mug/mL) prepared
      in three different serum pools from male and female cynomolgus monkeys.

PMID- 19842638
TI  - Influence of sulfur oxidation on the absorption and electronic energy levels of
      poly(thienothiophene) derivatives.
AB  - Two poly(thienothiophene) derivatives containing thieno[3,2-b]thiophene-4,4
      dioxide unit were synthesized by Pd-catalyzed Stille coupling method. They were
      poly(3,6-dihexyl-thieno[3,2-b]thiophene-4,4-dioxide vinylene) (P2) and poly(2,5
      diyl-3,6-dihexyl-thieno[3,2-b]thiophene-4,4-dioxide)-co-(2,5-diyl-thiophene)
      (P4). Poly(3,6-dihexyl-thieno[3,2-b] thiophene vinylene) (P1) and poly(2,5-diyl
      3,6-dihexyl-thieno[3,2-b] thiophene)-co-(2,5-diyl-thiophene) (P3) were
      synthesized for comparison with P2 and P4. After sulfur oxidation on the
      thienothiophene units, the absorption peaks of the polymer solutions were red
      shifted from 540 nm of P1 to 625 nm of P2 and from 445 nm of P3 to 520 nm of P4.
      The absorption peaks of the polymer films were red-shifted more significantly
      from 542 nm of P1 to 630 nm of P2 and from 480 nm of P3 to 564 nm of P4. The
      lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital
      (HOMO) energy levels also decreased a lot after the sulfur oxidation. In
      comparison with P1, the LUMO and HOMO energy levels of P2 decreased by 0.59 and
      0.35 eV, respectively. The levels were 0.87 and 0.39 eV lower in the LUMO and
      HOMO energy levels of P4 than in that of P3.

PMID- 19842636
TI  - Detection of endogenous dopamine changes in Drosophila melanogaster using fast
      scan cyclic voltammetry.
AB  - Drosophila melanogaster, the fruit fly, is a commonly used model organism because
      of its homology to mammals and facile genetic manipulations. However, the size of
      the nervous system is very small. We report a method to evoke and detect rapid
      changes in extracellular dopamine in a single nerve cord isolated from a
      Drosophila larva. Flies were genetically modified to express Channelrhodopsin-2,
      a blue-light activated cation channel, in only dopaminergic neurons.
      Extracellular dopamine changes were measured with fast-scan cyclic voltammetry at
      an implanted carbon-fiber microelectrode. Stimulations of 7 s with blue light
      result in an average peak dopamine concentration of 810 +/- 60 nM, similar to
      electrically-stimulated release in mammals. Stimulations repeated at 15 min
      intervals are stable for 65 min, allowing pharmacological experiments in the same
      sample. Peak duration is extended after cocaine or nisoxetine, inhibitors of the
      dopamine transporter (DAT). Release was reduced upon exposure to reserpine, which
      inhibits vesicular packaging. Chronic administration of NSD-1015, a dopamine
      synthesis inhibitor, decreased dopamine release and inhibited pupation, showing a
      link between neurotransmission and physiology. This is the first method to
      measure endogenous dopamine in an intact larval Drosophila nervous system and
      will allow studies of genetic and pharmacological manipulations of dopamine
      release and uptake.

PMID- 19842639
TI  - Energetic and entropic forces governing the attraction between polyelectrolyte
      grafted colloids.
AB  - The energetic and entropic interactions governing the attraction between like
      charged colloidal particles grafted with oppositely charged polyelectrolyte
      chains in a monovalent electrolyte are investigated computationally. We employ
      coarse-grained models of the colloids with varying surface and polyelectrolyte
      charges and Monte Carlo simulations to compute the potential of mean force
      between two colloidal particles as a function of their separation distance. By
      categorizing the potentials as attractive or purely repulsive, we obtain the
      extent and location of the attractive-force regime within the two-dimensional
      parameter space comprised of the colloid surface and polyelectrolyte charge. The
      attractive regime is found to occupy the inside of a hyperbola in this charge
      space, whose shape and size is determined by a complex interplay between
      energetic and entropic interactions. In particular, we find that the strength of
      attraction at short distances is governed by a balance between favorable
      energetic and entropic terms arising from polymer-bridging interactions,
      unfavorable energies arising from the mutual repulsion of the colloid surfaces
      and polyelectrolyte chains, and unfavorable entropies arising from the overlap
      and crowding effects of chains confined between the colloid surfaces. A
      phenomenological model is proposed to explain the hyperbolic shape of the
      attractive regime and make useful predictions about changes in its shape and
      location for conditions not investigated in this study.

PMID- 19842641
TI  - Linear and nonlinear spectroscopy of a porphyrin-squaraine-porphyrin conjugated
      system.
AB  - The linear and nonlinear absorption properties of a squaraine-bridged porphyrin
      dimer (POR-SQU-POR) are investigated using femto-, pico-, and nanosecond pulses
      to understand intramolecular processes, obtain molecular optical parameters, and
      perform modeling of the excited-state dynamics. The optical behavior of POR-SQU
      POR is compared with its separate porphyrin and squaraine constituent moieties.
      Linear spectroscopic studies include absorption, fluorescence, excitation and
      emission anisotropy, and quantum yield measurements. Nonlinear spectroscopic
      studies are performed across a wide range (approximately 150 fs, approximately 25
      ps, and approximately 5 ns) of pulsewidths and include two-photon absorption
      (2PA), single and double pump-probe, and Z-scan measurements with detailed
      analysis of excited-state absorption induced by both one- and two-photon
      absorption processes. The 2PA from the constituent moieties shows relatively
      small 2PA cross sections; below 10 GM (1 GM = 1 x 10(-50) cm4 s/photon) for the
      porphyrin constituent and below 100 GM for the squaraine constituent except near
      their one-photon resonances. In stark contrast, the composite POR-SQU-POR
      molecule shows 2PA cross sections greater than 10(3) GM over most of the spectral
      range from 850 to 1600 nm (the minimum value being 780 GM at 1600 nm). The
      maximum value is approximately 11,000 GM near the Nd:YAG laser wavelength of 1064
      nm. This broad spectral range of large 2PA cross sections is unprecedented in any
      other molecular system and can be explained by intramolecular charge transfer. A
      theoretical quantum-chemical analysis in combination with different experimental
      techniques allows insight into the energy-level structure and origin of the
      nonlinear absorption behavior of POR-SQU-POR.

PMID- 19842640
TI  - The significance of degenerate processes to enantioselective olefin metathesis
      reactions promoted by stereogenic-at-Mo complexes.
AB  - The present study provides spectroscopic and experimental evidence demonstrating
      that degenerate metathesis is critical to the effectiveness of this emerging
      class of chiral catalysts. Isolation and X-ray characterization of both
      diastereomeric complexes, as well as an examination of the reactivity and
      enantioselectivity patterns exhibited by such initiating neophylidenes in
      promoting ring-closing metathesis processes, are disclosed. Only when sufficient
      amounts of ethylene are generated and inversion at Mo through degenerate
      processes occurs at a sufficiently rapid rate is high enantioselectivity
      achieved, irrespective of the stereochemical identity of the initiating
      alkylidene (Curtin-Hammett kinetics). With diastereomeric metal complexes that
      undergo rapid interconversion, stereomutation at the metal center becomes
      inconsequential, and stereoselective synthesis of a chiral catalyst is not
      required.

PMID- 19842642
TI  - Synthesis of (E,Z)-1-alkoxy-3-acyloxy-2-methylpenta-1,3-dienes via Danishefsky
      type dienes or O-acylation of enones.
AB  - 1-Alkoxy-2-methyl-3-acyloxy-(E,E)-penta-1,3-dienes have been prepared applying
      among others a modified Danishefsky's general method, including chiral, racemic,
      and achiral derivatives.

PMID- 19842643
TI  - On the fluxional behavior of Dess-Martin periodinane: a DFT and 17O NMR study.
AB  - The structure and dynamics of the Dess-Martin periodinane, a I(V) iodobenzene
      compound widely used in organic synthesis as a mild oxidant, were studied by a
      combined (17)O NMR and DFT calculations approach. The results show that a
      degenerate [1,3] sigmatropic shift of iodine between the two oxygen atoms of each
      of the three acetoxy groups occurs in solution. The energy barrier of this
      process depends on the position of the acetoxy group with respect to the
      iodoxolone ring and is much lower than the energy barrier observed for similar
      I(III) compounds.

PMID- 19842644
TI  - Orientation correlation of sulfosuccinate-based room-temperature ionic liquids
      studied by polarization-resolved hyper-Rayleigh scattering.
AB  - Hyper-Rayleigh scattering (HRS) of sulfosuccinate-based room-temperature ionic
      liquids (RTILs), tetraalkylammonium salts of bis(2-ethylhexyl)sulfosuccinate
      (BEHSS(-)) and di(isobutyl)sulfosuccinate (DIBSS(-)), shows strong orientation
      correlation between sulfosuccinate ions for both BEHSS(-)-based and DIBSS(-)
      based RTILs. The hyperpolarizability and polarization resolved HRS, giving
      information at the dipolar electric order and at the quadrupolar electric order,
      respectively, have been measured as a function of the distance between
      sulfosuccinates by changing the size of the tetraalkylammonium ions constituting
      the ionic liquids. The variations obtained for the dipolar electric and
      quadrupolar electric components of the HRS intensity show the orientation
      correlation between sulfosuccinate ions. In particular, the weight parameter eta
      introduced for molecular assemblies deviates from a pure dipolar electric order
      that is generally expected for a homogeneous molecular solution. Nonmonotonic
      variations of eta with increasing the alkyl chain length of tetraalkylammonium
      ions indicate a transition in the organization of the anions from an homogeneous
      to an heterogeneous arrangement with increasing the intermolecular distance
      between sulfosuccinate ions due to the competition between the short- and long
      range molecular interactions.

PMID- 19842645
TI  - Self-segregation behavior of N-ethyl-pentadecafluorooctanamide-terminated
      polybutylene isophthalate and its effects on film morphology and wettability.
AB  - Polybutylene isophthalates (PBI) end-capped with N-ethyl
      pentadecafluorooctanamide were synthesized from dimethyl isophthalate, 1,4
      butanediol, and N-(2-hydroxyethyl)-perfluorooctanamide with fluorine monomer
      content from 0 to 5 mol %. The results demonstrated that there was an obvious
      gradient drop of fluorine concentration from the film surface down to the inner
      bulk, and the enriched perfluoroalkyl segments covered the rough disordered
      crystalline topography of PBI, leading to greatly decreased roughness values of
      fluorinated films. Moreover, the film with only 3 mol % fluorine monomer content
      exhibited the surface tension of 16.7 mN/m, even lower than that of
      polytetrafluoroethylene (18.5 mN/m), indicating that the fluorinated groups not
      only enriched on the film surface but also tended to orient the CF(3) group
      upward. This study is of significance for further understanding the effects of
      polymeric structural factors on the migration ability of fluorine in the polymer
      film.

PMID- 19842646
TI  - Effect of water/carboxymethylcellulose gel on the excimer formation of polyamine
      ligands functionalized with naphthalene.
AB  - Formation of intramolecular excimers was studied for the compounds 6,20-bis
      naphthalene-2-ylmethyl-3,6,9,17,20,23,29,30-octaaza-tricyclo[23.3.1.1] triaconta
      1(29),11,13,15(30),25,27-hexane (L1), a bis-naphthalene derivative, and N1-(2
      {bis-[2-(3-amino-propylamino)-ethyl]-amino}-ethyl)-propane-1,3-diamine (L2), a
      tris-naphthalene derivative, incorporated in gels of carboxymethylcellulose
      sodium salt. Excimers are formed through dynamic processes as well as from ground
      state dimers. A mathematical treatment including preformed dimers was used to
      split the static and dynamic contributions in the excimer/monomer emission ratio.
      In the case of compound L1, the activation energy for excimer formation in water
      is 11 kJ mol(-1) and experimental evidence that the dynamic terms are identical
      in water and in the gel was achieved. On the other hand, ground state dimers are
      extremely favorable in the gel with an equilibrium constant of 8.2 at 25 degrees
      C. On the contrary, in the case of compound L2, the ground state dimers are
      observed in water but not in the gel. The results were interpreted as reflecting
      a balance between specific interactions (hydrogen bond) and confinement effects.

PMID- 19842647
TI  - A straightforward method for the colorimetric detection of endogenous biological
      cyanide.
AB  - Corrin-based chemosensors allow the rapid and selective colorimetric detection of
      endogenous biological cyanide. The color change from orange to violet can be
      easily observed with the "naked eye" (Deltalambda(max) = 51 nm). The methodology
      works directly in the biological matrix without time-consuming sample
      pretreatment and the use of special reaction conditions. It was possible to study
      the enzymatic release of cyanide from its biological precursor linamarin with
      diffuse reflectance UV-visible (DRUV-vis) spectroscopy on a freshly prepared
      biological surface. These experiments were accompanied by stopped-flow kinetic
      measurements under homogeneous conditions. Detection in the biological sample is
      based on the selective coordination of cyanide to the metal-based chemosensor as
      proven by UV-vis and (1)H NMR spectroscopy. Examples of applications during food
      manufacturing are given.

PMID- 19842648
TI  - Vibrational spectroscopy and dynamics of water confined inside reverse micelles.
AB  - In this work, we combine atomistic molecular dynamics simulations with
      theoretical vibrational spectroscopy to study the properties of water confined
      inside bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles. This approach is
      found to successfully reproduce the experimental spectra, rotational anisotropy
      decays, and spectral diffusion time-correlation functions as a function of
      micelle size. These results are interpreted in terms of water molecules in
      different hydrogen bonding environments. One interesting result from our
      simulation, not directly accessible experimentally, involves the distance from
      the surfactant headgroup/water interface over which the dynamical properties of
      water become bulk-like. We find that this distance varies with micelle size,
      casting doubt on the core/shell model. In particular, the distance increases with
      decreasing micelle size, and hence decreasing radius of curvature of the
      interface. We suggest that this arises from curvature-induced frustration. We
      also find that the dynamics in the smallest micelle studied is extremely slow-
      relaxation is still incomplete by 1 ns. As in other glassy systems with
      collective relaxation, our time-correlation functions can be fit to stretched
      exponentials, in this case with very small exponents.

PMID- 19842649
TI  - Steric and solvation effects in ionic S(N)2 reactions.
AB  - This paper explores the contribution of solvation to the overall steric effects
      of S(N)2 reactions observed in solution. The reactions of chloride ion with a
      series of alkyl chloronitriles, RCH(CN)Cl (R = methyl, ethyl, isopropyl, tert
      butyl) were investigated both experimentally and theoretically. These reactions
      serve as a model system for the parent reactions, Cl(-) + RCH(2)Cl, which are too
      slow to measure. Each additional substitution at the beta-carbon lowers the
      reactivity, clearly demonstrating a steric hindrance effect. The magnitude of the
      steric effect, however, is not significantly different in the gas phase and in
      solution. We conclude that the solvation energies of the corresponding S(N)2
      transition states must be similar regardless of size of the substituent. This
      lack of size dependence in the current system is in sharp contrast with many
      other ionic systems such as ionization of simple alkyl alcohols, where solvation
      depends strongly on size. We propose that the weak size dependence results from
      the compensation between a direct shielding effect of the substituent and an
      indirect ionic solvation effect, which arises from the geometric perturbations
      introduced by the substitution. The conclusion is further supported by
      calculations using polarizable continuum models and QM/MM simulations.

PMID- 19842650
TI  - Synthesis of SnS quantum dots.
AB  - Highly mondispersed SnS nanocrystals have been synthesized using ethanolamine
      ligands. SnS nanocrystals are small enough to be in the quantum confinement
      regime.

PMID- 19842651
TI  - The road to 13-15 nano structures: structures and energetics of (MYH(2))(4)
      tetramers (M = B, Al, Ga; Y = N, P, As).
AB  - A(III)B(V) compounds are important for the development of advanced ceramic
      semiconductor and nanoelectronic materials, solar cell elements, and light
      emitting diodes. A series of these group 13-15 compounds of the general formula
      M(4)Y(4)H(8) (M = B, Al, Ga; Y = N, P, As) has been theoretically studied at the
      B3LYP/TZVP level of theory. The stability of different isomer structures is
      discussed to reveal the competitiveness of group 13-13, group 13-15, and group 15
      15 bonding. Preferential bonding patterns are established, and trends in the
      stability with respect to M and Y are also discussed. New structural types,
      featuring perfectly planar M(4) and Y(4) rings, have been established.

PMID- 19842652
TI  - Investigation of the coordination interactions of S-(pyridin-2-ylmethyl)-L
      cysteine ligands with M(CO)(3)(+) (M = Re, (99m)Tc).
AB  - Development of new ligands for fac-M(OH(2))(3)(CO)(3)(+) (M = Re, (99m)Tc) led
      the investigation with S-(pyridin-2-ylmethyl)-l-cysteine, 1. The ligand 1 has
      potential to coordinate with the metal through three different tridentate modes:
      tripodal through cysteine (O,N,S) and two linear involving the S-pyridyl and
      cysteine (O,S,N(Py), N,S,N(Py)). From the reaction with 1, two species were
      observed in the (1)H NMR, where the primary product was the linear fac
      Re(N,S,N(Py)-1)(CO)(3)(+), 2a, complex. To identify the coordination mode of the
      minor product, functionalized analogues of 1 were prepared from S-(pyridin-2
      ylmethyl)-Boc-l-cysteine-methyl ester, 3, with orthogonal protecting groups on
      the C terminus (methyl ester) in S-(pyridin-2-ylmethyl)-l-cysteine methyl ester,
      4, or N terminus (Boc) in S-(pyridin-2-ylmethyl)-Boc-l-cysteine, 6, that
      specifically directed the coordination mode of fac-M(H(2)O)(3)(CO)(3)(+) to
      either N,S,N(Py) or O,S,N(Py), respectively. Two diastereomers [fac
      Re(CO)(3)(N,S,N(Py)-4)](+), 5a and 5b, were observed and independently
      characterized by X-ray structure analysis and NMR in high yield with 4.
      Surprisingly, the O,S,N(Py) Re complex with ligand 6 was not observed and
      simplified versions, 3-(pyridin-2-ylmethylthio) propanoic acid, 7, and 2-(pyridin
      2-ylmethylthio)acetic acid, 8, were investigated. Ligand 7 did not yield the
      desired linear tridentate O,S,N(Py) product. However, the shorter ligand 8 formed
      fac-Re(CO)(3)(O,S,N(Py)-8), 9, in high yield. (99m)Tc labeling studies were
      conducted and yielded similar results to the rhenium complex and effective (>99%)
      at 10(-5) M ligand concentration.

PMID- 19842653
TI  - Coaxial cross-diffusion through carbon nanotubes.
AB  - We present results from nonequilibrium molecular dynamics experiments describing
      the relaxation of local concentrations at two reservoirs, initially filled with
      water (W) and acetonitrile (ACN), as they become connected through a membrane
      composed of (16,16) carbon nanotubes. Within the hydrophobic nanotube cavities,
      the equilibrium concentrations contrast sharply to those observed at the
      reservoirs, with a clear enhancement of ACN, in detriment of W. From the
      dynamical side, the relaxation involves three well-differentiated stages; the
      first one corresponds to the equilibration of individual concentrations within
      the nanotubes. An intermediate interval with Fickian characteristics follows,
      during which the overall transport can be cast in terms of coaxial opposite
      fluxes, with a central water domain segregated from an external ACN shell, in
      close contact with the tube walls. We also found evidence of a third, much
      slower, mechanism to reach equilibration, which involves structural modifications
      of tightly bound solvation shells, in close contact with the nanotube rims.

PMID- 19842654
TI  - Theoretical and experimental study of the rovibrational spectrum of He(2)-CO.
AB  - We report calculated microwave and infrared ro-vibrational transitions of the van
      der Waals complex He(2)-CO. The calculations were done using a product basis and
      a Lanczos eigensolver, together with He-CO and He-He potential functions taken
      from the literature. The results are found to be in good agreement with
      previously reported experimental results, and they enable the experimental
      assignments to be clarified, augmented, and (in one case) corrected. Unlike some
      other van der Waals complexes with two He atoms such as He(2)-N(2)O, it is not
      possible to associate a set of energy levels with the "torsional" motion of the
      two He atoms on a ring encircling the dopant (in this case CO). Although we
      assume that the dipole moment is along the CO axis we find nonetheless that many
      transitions have appreciable intensity due to ro-vibrational coupling.

PMID- 19842655
TI  - Self-template synthesis of CdIn(2)O(4) hollow spheres and effects of cd/in molar
      ratios on its morphologies.
AB  - CdIn(2)O(4) hollow spheres were synthesized by a self-template method. Cadmium
      nitrate (Cd(NO(3))(2).4H(2)O) and indium nitrate (In(NO(3))(3).4.5H(2)O) were
      used as raw materials. XRD and SEM were employed to characterize the structures
      and morphologies of as-grown samples. The effects of Cd/In ratios on the
      compositions, morphologies, and photocatalytic activities have been
      systematically investigated. A self-template growth mechanism of CdIn(2)O(4)
      hollow spheres was proposed. And pure phase of CdIn(2)O(4) can be obtained with
      Cd/In ratio of 1.3:2 annealing at 800 degrees C according to our experiments. The
      sample with the Cd/In ratio of 1.4:2 exhibited the highest photocatalytic
      efficiency, and more than 80% of Methylene Blue molecules can be decomposed in
      180 min.

PMID- 19842656
TI  - Development of a rapid determination of pesticides in coated seeds using a high
      performance liquid chromatography-UV detection system.
AB  - For the determination of pesticides in coated seeds, this study compared two HPLC
      UV methods, using a short column or a conventional column, as well as two
      extraction procedures, by ultrasonic extraction at room temperature or by
      pressurized liquid extraction (PLE). The comparison of selected column
      performances showed that the short column enabled the 3-fold reduction of
      analysis time (ca. 9 min vs 29 min) and eluent consumption (ca. 6.1 mL vs 20.8
      mL) for the separation of five insecticides (bitertanol, fludioxonil,
      imidacloprid, metalaxyl-M and tefluthrin) and one bird repellent (anthraquinone)
      without altering peak resolutions. Recovery rates for pressurized liquid
      extraction at 120 degrees C were similar (between 84% and 102%) to those obtained
      by ultrasonication. Both methods were then applied for the extraction of loaded
      seeds. Rates for ultrasonic extraction at room temperature were lower (from 16%
      to 95%) than those observed for recovery tests, unlike PLE at 120 degrees C which
      showed good rates, ranging between 82% and 95%, for all the loaded pesticides.

PMID- 19842657
TI  - Zeolitic polyoxometalate-based metal-organic frameworks (Z-POMOFs): computational
      evaluation of hypothetical polymorphs and the successful targeted synthesis of
      the redox-active Z-POMOF1.
AB  - The targeted design and simulation of a new family of zeolitic metal-organic
      frameworks (MOFs) based on benzenedicarboxylate (BDC) as the ligand and epsilon
      type Keggin polyoxometalates (POMs) as building units, named here Z-POMOFs, have
      been performed. A key feature is the use of the analogy between the connectivity
      of silicon in dense minerals and zeolites with that of the epsilon-type Keggin
      POMs capped with Zn(II) ions. Handling the epsilon-Keggin as a building block, a
      selection of 21 zeotype structures, together with a series of dense minerals were
      constructed and their relative stabilities computed. Among these Z-POMOFs, the
      cristobalite-like structure was predicted to be the most stable structure. This
      prediction has been experimentally validated by the targeted synthesis of the
      first experimental Z-POMOF structure, which was strikingly found to possess the
      cristobalite topology, with three interpenetrated networks. Crystals of
      [NBu(4)](3)[PMo(V)(8)Mo(VI)(4)O(36)(OH)(4)Zn(4)(BDC)(2)].2H(2)O (Z-POMOF1) have
      been isolated under hydrothermal conditions from the reduction of ammonium
      heptamolybdate in the presence of phosphorous acid and Zn(II) ions.
      Tetrabutylammonium cations play the role of counterions and space-filling agents
      in this tridimensional interpenetrated framework. Moreover, the electrochemistry
      of the epsilon-Keggin POM is maintained and can be exploited in the insoluble Z
      POMOF1 framework, as demonstrated by the electrocatalytic reduction of bromate.

PMID- 19842658
TI  - A bond-bond description of the intermolecular interaction energy: the case of the
      weakly bound acetylene-hydrogen complex.
AB  - A new semiempirical potential energy surface (PES) for the acetylene-hydrogen
      system has been derived by using the recently introduced bond-bond methodology.
      The proposed PES, expressed in an analytic form suitable for molecular dynamics
      simulations, involves a limited number of parameters, each one having a physical
      meaning and allowing the accurate description of the system also in the less
      stable configurations. The analysis of novel integral cross sections data,
      measured with nearly effusive molecular beams, combined with that of available
      pressure broadening coefficients of isotropic Raman lines at 143 K and IR lines
      at 173 and 295 K of C(2)H(2) in H(2), provides a test of the reliability of the
      proposed PES and suggests also some refinements. An extensive comparison with a
      recent ab initio potential is also exploited.

PMID- 19842659
TI  - Planar hepta-, octa-, nona-, and decacoordinate first row d-block metals enclosed
      by boron rings.
AB  - Possible planar hypercoordinate molecules with first row d-block metal atoms in
      the centers of boron rings are explored comprehensively by density-functional
      theory (DFT) computations. Many optimized MB(n) (n = 7, 8, 9, and 10) neutral and
      charged clusters have local D(nh) minima, although these may not be the most
      stable isomers. The larger B(9) and B(10) rings are versatile in accommodating
      first row d-block metals, whereas the more compact B(8) ring only can enclose
      smaller transition metals (such as Mn, Fe, and Co) effectively. Delocalized pi
      and radial molecular orbitals involving boron are crucial in stabilizing these
      highly symmetrical planar hypercoordinate molecules. Early and middle transition
      metal d-orbitals participate in metal-boron covalent bonding, whereas partial
      ionic bonding is more important for the late d-block elements. Potential energy
      surface scans established several of these species to have planar hypercoordinate
      global minima: D(8h) FeB(8)(2-) was identified here, and D(8h) CoB(8)(-) and
      D(9h) FeB(9)(-) were identified in an earlier complementary study.

PMID- 19842660
TI  - Exploring the importance of piperazine N-atoms for sigma(2) receptor affinity and
      activity in a series of analogs of 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4
      tetrahydronaphthalen-1-yl)propyl]piperazine (PB28).
AB  - sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1
      yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in
      breast cancer cells, was taken as a template to prepare new analogs. One of the
      two basic N-atoms was alternatively replaced by a methine or converted into an
      amide or ammonium function, with the aim of finding out which of them was
      essential for sigma(2) receptor affinity and activity. Some simply 4-substituted
      1-cyclohexylpiperazines were also investigated. None of the compounds was as high
      affinity as 7 (sigma(2)K(i) = 0.68, sigma(1)K(i) = 0.38 nM), proving that both
      basic N-atoms ensure better sigma(2) receptor binding. Amide 36 emerged as high
      affinity (K(i) = 0.11 nM) and noteworthy() selective (1627-fold) sigma(1) ligand.
      Small N-cyclohexylpiperazine 59 displayed the highest sigma(2) affinity (K(i) =
      4.70 nM). The sigma(2)/sigma(1) selectivities were generally low.
      Antiproliferative assay in SK-N-SH cells revealed piperidines 24 and 15 as
      putative sigma(2) agonists (EC(50)s 1.40 and 3.64 muM respectively) more potent
      than 7.

PMID- 19842661
TI  - Discovery of 3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-ones as potent, highly
      selective, and orally bioavailable inhibitors of the human protooncogene proviral
      insertion site in moloney murine leukemia virus (PIM) kinases.
AB  - Pim-1, Pim-2, and Pim-3 are a family of serine/threonine kinases which have been
      found to be overexpressed in a variety of hematopoietic malignancies and solid
      tumors. Benzothienopyrimidinones were discovered as a novel class of Pim
      inhibitors that potently inhibit all three Pim kinases with subnanomolar to low
      single-digit nanomolar K(i) values and exhibit excellent selectivity against a
      panel of diverse kinases. Protein crystal structures of the bound Pim-1 complexes
      of benzothienopyrimidinones 3b (PDB code 3JYA), 6e (PDB code 3JYO), and 12b (PDB
      code 3JXW) were determined and used to guide SAR studies. Multiple compounds
      exhibited potent antiproliferative activity in K562 and MV4-11 cells with
      submicromolar EC(50) values. For example, compound 14j inhibited the growth of
      K562 cells with an EC(50) value of 1.7 muM and showed K(i) values of 2, 3, and
      0.5 nM against Pim-1, Pim-2, and Pim-3, respectively. These novel Pim kinase
      inhibitors efficiently interrupted the phosphorylation of Bad in both K562 and
      LnCaP-Bad cell lines, indicating that their potent biological activities are
      mechanism-based. The pharmacokinetics of 14j was studied in CD-1 mice and shown
      to exhibit bioavailability of 76% after oral dosing. ADME profiling of 14j
      suggested a long half-life in both human and mouse liver microsomes, good
      permeability, modest protein binding, and no CYP inhibition below 20 muM
      concentration.

PMID- 19842662
TI  - Extremely efficient alkane oxidation by a new catalytic reagent
      H(2)O(2)/Os(3)(CO)(12)/pyridine.
AB  - Triosmium dodecacarbonyl catalyzes a very efficient oxidation of alkanes by
      H(2)O(2) in MeCN to afford alkyl hydroperoxides (primary products) as well as
      alcohols and ketones (aldehydes) at 60 degrees C if pyridine is added in a low
      concentration. Turnover numbers attain 60,000, and turnover frequencies are up to
      24,000 h(-1).

PMID- 19842663
TI  - [Os(IV)Cl(5)(Hazole)](-) complexes: synthesis, structure, spectroscopic
      properties, and antiproliferative activity.
AB  - By exploring the Anderson type rearrangement reactions, osmium(IV) complexes of
      the general formula [cation](+)[Os(IV)Cl(5)(Hazole)](-), where [cation](+) = n
      Bu(4)N(+), Hazole = 1H-pyrazole (Hpz) (1), 1H-indazole (Hind) (2), 1H-imidazole
      (Him) (3), 1H-benzimidazole (Hbzim) (4), 1H,2,4-triazole (Htrz) (5), have been
      synthesized. To improve water solubility of tetrabutylammonium compounds,
      complexes with [cation](+) = Na(+) [Hazole = Hpz 6), Hind (7), Htrz (8)] or
      H(2)azole(+) [Hazole = Hpz (9), Hind (10), Htrz (11)] have been also prepared
      with the aim of testing them for cytotoxicity in cancer cells. In addition, the
      preparation of the complex {(n-Bu(4)N)(2)[Os(IV)Cl(6)]}(2)[Os(IV)Cl(4)(Him)(2)]
      (12) is also reported. The compounds have been comprehensively characterized by
      elemental analysis, electrospray ionization (ESI) mass spectrometry, spectroscopy
      (IR, UV-vis, 1D and 2D NMR), cyclic voltammetry, X-ray crystallography (1-6 and
      12) and magnetic susceptibility (5). Complexes 6, 7, 9 are kinetically inert in
      aqueous solution and resistant to hydrolysis. Compounds 6-11 were found to
      possess modest antiproliferative acitivity in vitro against CH1 (ovarian
      carcinoma), A549 (non-small cell lung carcinoma), and SW480 (colon
      adenocarcinoma) cells with IC(50) values in the 10(-4) M concentration range.
      Replacement of azolium cations by sodium had significant effects; cytotoxicity
      increased in the case of the pyrazole system from 3 (A549) to the 5.5-fold (CH1).

PMID- 19842664
TI  - Design, synthesis, and structure-activity relationship of indole-3-glyoxylamide
      libraries possessing highly potent activity in a cell line model of prion
      disease.
AB  - Transmissible spongiform encephalopathies (TSEs) are a family of invariably fatal
      neurodegenerative disorders for which no effective curative therapy currently
      exists. We report here the synthesis of a library of indole-3-glyoxylamides and
      their evaluation as potential antiprion agents. A number of compounds
      demonstrated submicromolar activity in a cell line model of prion disease
      together with a defined structure-activity relationship, permitting the design of
      more potent compounds that effected clearance of scrapie in the low nanomolar
      range. Thus, the indole-3-glyoxylamides described herein constitute ideal
      candidates to progress to further development as potential therapeutics for the
      family of human prion disorders.

PMID- 19842666
TI  - Electronic structure and spectroscopy of [Ru(tpy)(2)](2+),
      [Ru(tpy)(bpy)(H(2)O)](2+), and [Ru(tpy)(bpy)(Cl)](+).
AB  - We use a combined, theoretical and experimental, approach to investigate the
      spectroscopic properties and electronic structure of three ruthenium polypyridyl
      complexes, [Ru(tpy)(2)](2+), [Ru(tpy)(bpy)(H(2)O)](2+), and [Ru(tpy)(bpy)(Cl)](+)
      (tpy = 2,2':6',2''-terpyridine and bpy = 2,2'-bipyridine) in acetone,
      dichloromethane, and water. All three complexes display strong absorption bands
      in the visible region corresponding to a metal-to-ligand-charge-transfer (MLCT)
      transition, as well as the emission bands arising from the lowest lying (3)MLCT
      state. [Ru(tpy)(bpy)(Cl)](+) undergoes substitution of the Cl(-) ligand by H(2)O
      in the presence of water. Density functional theory (DFT) calculations
      demonstrate that the triplet potential energy surfaces of these molecules are
      complicated, with several metal-centered ((3)MC) and (3)MLCT states very close in
      energy. Solvent effects are included in the calculations via the polarizable
      continuum model as well as explicitly, and it is shown that they are critical for
      proper characterization of the triplet excited states of these complexes.

PMID- 19842665
TI  - White OLED with a single-component europium complex.
AB  - A new direction for white organic light-emitting devices is shown, fabricated
      from a novel europium complex; this single component contains a double emission
      center of bluish-green and red, combined to a give a pure white emission (CIE x =
      0.34 and y = 0.35).

PMID- 19842667
TI  - Nonconventional behavior of NCN-chelated organoantimony(III) sulfide and
      isolation of cyclic organoantimony(III) bis(pentasulfide).
AB  - Organoantimony(III) sulfide (1) containing the NCN chelating ligand L [L = 2,6
      (CH(2)NMe(2))(2)C(6)H(3)] displays unusual dual behavior, being dimeric
      (LSbS)(2), with the central Sb(2)S(2) core, in the solid state but monomeric in
      solution. Sulfide 1 reacts with elemental S to give the unprecedented cyclic
      bis(pentasulfide) LSb(mu-S(5))(2)SbL (2) with the central 12-membered ring
      Sb(2)S(10).

PMID- 19842668
TI  - Zeolitic imidazolate framework membrane with molecular sieving properties by
      microwave-assisted solvothermal synthesis.
AB  - A zeolitic imidazolate framework (ZIF-8) as member of the metal-organic framework
      family has been crystallized as a thin porous layer on an asymmetric ceramic
      support. Hydrogen can be selected from other gases by molecular sieving.

PMID- 19842669
TI  - 14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and
      related opioids. Further examples of pseudoirreversible mu opioid receptor
      antagonists.
AB  - 14beta-4'-Chlorocinnamoylaminodihydronormorphinone (2a), and analogues, are
      selective pseudoirreversible antagonists of the mu opioid receptor (MOR). The
      preparation of analogues with ethynic bonds, replacing the ethenic bond of 2a, is
      described. The new ligands, in mouse antinociceptive assays, had
      pseudoirreversible MOR antagonist activity, which, in the case of 8b was of
      longer duration than that of 2a. The related codeinone (9b) had only antagonist
      activity in vivo, in contrast to 2a's codeinone equivalent 3a, which had potent
      antinociceptive activity.

PMID- 19842670
TI  - A background level of oxygen-containing aromatics for synthetic control of carbon
      nanotube structure.
AB  - Growth enhancers, most notably water, have been reported to increase catalyst
      activity, despite constituting 0.02% of the growth ambient, resulting in dramatic
      increases in vertically aligned carbon nanotube (CNT) forests. We demonstrate a
      surprising second function of the growth enhancer, i.e., its ability to control
      the structure of the CNTs exemplified by highly selective double-walled carbon
      nanotube synthesis using oxygen-containing aromatics. This approach provides an
      easy and convenient method to grow various kinds of nanotubes from the same
      catalyst and same growth conditions.

PMID- 19842671
TI  - Nanoporous pt-co alloy nanowires: fabrication, characterization, and
      electrocatalytic properties.
AB  - Nanoporous Pt-Co alloy nanowires were synthesized by electrodeposition of Co-rich
      Pt(1)Co(99) alloy into anodic aluminum oxide (AAO) membranes, followed by a
      dealloying treatment in a mild acidic medium. These nanowires consist of porous
      skeletons with tiny pores of 1-5 nm and crystalline ligaments of 2-8 nm.
      Morphological and compositional evolutions of the porous Pt-Co nanowires upon
      dealloying were investigated, and their formation mechanism is discussed. The
      nanoporous Pt-Co alloy nanowires are found to exhibit distinctly enhanced
      electrocatalytic activities toward methanol oxidation as compared to the current
      state-of-the-art Pt/C and PtCo/C catalysts, thus showing substantial promise as
      efficient anode electrocatalysts in direct methanol fuel cells.

PMID- 19842673
TI  - Nanocarrier cross-linking density and pH sensitivity regulate intracellular gene
      transfer.
AB  - Treatment of diseases on the molecular level by genetic material is limited by
      effective delivery mechanisms. We focused on the synthesis of a pH-sensitive gene
      delivery vehicle based on dimethylaminoethyl methacrylate (DMAEMA) with tunable
      swelling, cross-linking density, and DNA release kinetics within the endosomal pH
      range. Our strategy, which utilized a single step for DNA encapsulation, enhanced
      gene transfection efficiency and reduced cytotoxicity relative to
      polyethyleneimine (PEI) and poly-L-lysine (PLL).

PMID- 19842674
TI  - Quantum chemical study on UV-vis spectra of microhydrated iodine dimer radical
      anion.
AB  - UV-vis spectral properties of I(2)(*-).nH(2)O systems are reported based on ab
      initio quantum chemical calculations. Second order Moller-Plesset perturbation
      theory is applied for geometry search and time dependent density functional
      theory is applied to study excited state properties. Relativistic corrections are
      considered for all the calculations. Geometry search is carried out applying
      simulated annealing combined with Monte Carlo sampling method. Strong optical
      absorption band of these hydrated clusters, I(2)(*-).nH(2)O in the UV-vis region
      is assigned to sigma(g) --> sigma(u)* type valence electron transition in
      contrast to charge transfer to solvent spectra in I(-).nH(2)O systems. Simulated
      optical absorption profile of I(2)(*-).8H(2)O system is in excellent agreement
      with the reported aqueous phase spectrum of iodine dimer radical anion.

PMID- 19842672
TI  - Polymeric nanoparticle-based activatable near-infrared nanosensor for protease
      determination in vivo.
AB  - We report here a new protease activatable strategy based on a polymer
      nanoparticle platform. This nanosensor delivers chemically labeled matrix
      metalloproteinase (MMP)-activatable fluorogenic peptides to the specific MMPs of
      interest in vivo. Intravenous administration of the nanosensor in an MMP-positive
      SCC-7 xenograft tumor and a colon cancer mouse model verified the enzyme
      specificity of the nanosensor in vivo. The design platform of the nanosensor is
      flexible and can be fine-tuned for a wide array of applications such as the
      detection of biomarkers, early diagnosis of disease, and monitoring therapeutic
      efficacy.

PMID- 19842675
TI  - Palladium-catalyzed carbonylative cycloisomerization of gamma-propynyl-1,3
      diketones: a concise route to polysubstituted furans.
AB  - Di- and trisubstituted furan derivatives have been efficiently synthesized via
      palladium(II)-catalyzed intramolecular carbonylative cycloisomerization of gamma
      propynyl-1,3-diketones with aryl iodides and carbon monoxide. The mechanism
      suggests that in situ generated acylpalladium species from the carbonylation of
      aryl iodide initiates the reaction followed by cyclization of the enolized isomer
      of a 1,3-diketone substrate via carbon-carbon triple bond activation.

PMID- 19842676
TI  - Nanowire transformation by size-dependent cation exchange reactions.
AB  - The unique properties of nanostructured materials enable their transformation
      into complex, kinetically controlled morphologies that cannot be obtained during
      their growth. Solution-phase cation-exchange reactions can transform sub-10 nm
      nanocrystals/nanorods into varying compositions and superlattice structures;
      however, because of their small size, cation-exchange reaction rates are
      extremely fast, which limits control over the transformed products and
      possibilities for obtaining new morphologies. Nanowires are routinely synthesized
      via gas-phase reactions with 5-200 nm diameters, and their large aspect ratios
      allow them to be electrically addressed individually. To realize their full
      potential, it is desirable to develop techniques that can transform nanowires
      into tunable but precisely controlled morphologies, especially in the gas-phase,
      to be compatible with nanowire growth schemes. We report transformation of single
      crystalline cadmium sulfide nanowires into composition-controlled Zn(x)Cd((1-x))S
      nanowires, core-shell heterostructures, metal-semiconductor superlattices (Zn
      Zn(x)Cd((1-x))S), single-crystalline ZnS nanotubes, and eventually metallic Zn
      nanowires by utilizing size-dependent cation-exchange reaction along with
      temperature and gas-phase reactant delivery control. This versatile synthetic
      ability to transform nanowires offers new opportunities to study size-dependent
      phenomena at the nanoscale and tune their chemical/physical properties to design
      reconfigurable circuits.

PMID- 19842677
TI  - High-performance single-crystalline arsenic-doped indium oxide nanowires for
      transparent thin-film transistors and active matrix organic light-emitting diode
      displays.
AB  - We report high-performance arsenic (As)-doped indium oxide (In(2)O(3)) nanowires
      for transparent electronics, including their implementation in transparent thin
      film transistors (TTFTs) and transparent active-matrix organic light-emitting
      diode (AMOLED) displays. The As-doped In(2)O(3) nanowires were synthesized using
      a laser ablation process and then fabricated into TTFTs with indium-tin oxide
      (ITO) as the source, drain, and gate electrodes. The nanowire TTFTs on glass
      substrates exhibit very high device mobilities (approximately 1490 cm(2) V(-1) s(
      1)), current on/off ratios (5.7 x 10(6)), steep subthreshold slopes (88 mV/dec),
      and a saturation current of 60 microA for a single nanowire. By using a self
      assembled nanodielectric (SAND) as the gate dielectric, the device mobilities and
      saturation current can be further improved up to 2560 cm(2) V(-1) s(-1) and 160
      microA, respectively. All devices exhibit good optical transparency
      (approximately 81% on average) in the visible spectral range. In addition, the
      nanowire TTFTs were utilized to control green OLEDs with varied intensities.
      Furthermore, a fully integrated seven-segment AMOLED display was fabricated with
      a good transparency of 40% and with each pixel controlled by two nanowire
      transistors. This work demonstrates that the performance enhancement possible by
      combining nanowire doping and self-assembled nanodielectrics enables silicon-free
      electronic circuitry for low power consumption, optically transparent, high
      frequency devices assembled near room temperature.

PMID- 19842678
TI  - A phospho-directed macroporous alumina-silica nanoreactor with multi-functions.
AB  - A phospho-directed nanoreactor with multiple functions is reported. Alumina
      functionalized macroporous ordered silica foams (Al-MOSF) have been developed
      with large pore size, high pore volume (1.6 cm(3)/g), and a surface area of 186
      m(2)/g rich in coordination unsaturated Al species, which can be used as phospho
      directed nanoreactors for integrated in situ digestion and in situ
      phosphoisolation. By directly adding Al-MOSF to the conventional in-solution
      digestion system, both enzymes and proteins are quickly enriched in the
      macropores of the reactor to achieve a fast proteolysis without increasing the
      enzyme/protein concentration or using a preimmobilization process, thus the
      digestion time and the cost can be greatly reduced. Meanwhile, due to the chemo
      affinity between alumina and phosphor groups, the Al-MOSF reactor can in situ
      isolate specific products of the enzymatic reaction (i.e., phosphopeptides) and
      release the nonspecific peptides to the solution. This strategy is simple,
      efficient, and successfully applied in the detection of phosphoproteins in real
      samples.

PMID- 19842679
TI  - Effect of the electron-phonon interaction on the luminescence properties of iron
      ions in YAG crystal.
AB  - High-resolution photoluminescence spectra of Fe:YAG crystals were recorded in the
      temperature range 10-150 K with different excitation energies, ranging from the
      band gap energy (6.88 eV) down to selective excitation of Fe(3+) ions (2.40 eV).
      Iron levels fine structure is found in the zero phonon lines, whose
      characteristics hint at the presence of the doping Fe(3+) ion in the tetrahedral
      site with a dynamic Jahn-Teller effect inherent in the (4)T(1) excited states.
      The analysis of the zero phonon interactions with acoustic phonons was achieved
      through linear and quadratic electron-phonon coupling models, and the Huang-Rhys
      factor, the Debye temperature, and the electron-phonon coupling were calculated
      in the framework of the Debye approximation by including only the Raman two
      phonon process. The interactions with lattice phonons were studied, and the
      results were found to be correspondent to the expected results from previous
      vibrational data.

PMID- 19842680
TI  - Controllable synthesis of single-walled carbon nanotube framework membranes and
      capsules.
AB  - Controlling the morphology of membrane components at the nanometer scale is
      central to many next-generation technologies in water purification, gas
      separation, fuel cell, and nanofiltration applications. Toward this end, we
      report the covalent assembly of single-walled carbon nanotubes (SWNTs) into three
      dimensional framework materials with intertube pores controllable by adjusting
      the size of organic linker molecules. The frameworks are fashioned into
      multilayer membranes possessing linker spacings from 1.7 to 3.0 nm, and the
      resulting framework films were characterized, including transport properties.
      Nanoindentation measurements by atomic force microscopy show that the spring
      constant of the SWNT framework film (22.6 +/- 1.2 N/m) increased by a factor of 2
      from the control value (10.4 +/- 0.1 N/m). The flux ratio comparison in a
      membrane-permeation experiment showed that larger spacer sizes resulted in larger
      pore structures. This synthetic method was equally efficient on silica
      microspheres, which could then be etched to create all-SWNT framework, hollow
      capsules approximately 5 mum in diameter. These hollow capsules are permeable to
      organic and inorganic reagents, allowing one to form inorganic nanoparticles, for
      example, that become entrapped within the capsule. The ability to encapsulate
      functional nanomaterials inside perm-selective SWNT cages and membranes may find
      applications in new adsorbents, novel catalysts, and drug delivery vehicles.

PMID- 19842681
TI  - Shock tube and theory investigation of cyclohexane and 1-hexene decomposition.
AB  - The decomposition of cyclohexane (c-C(6)H(12)) was studied in a shock tube using
      the laser-schlieren technique over the temperature range 1300-2000 K and for 25
      200 Torr in mixtures of 2%, 4%, 10%, and 20% cyclohexane in Kr. Vibrational
      relaxation of the cyclohexane was also examined in 10 experiments covering 1100
      1600 K for pressures below 20 Torr, and relaxation was found to be too fast to
      allow resolution of incubation times. The dissociation of 1-hexene (1-
      C(6)H(12)), apparently the sole initial product of cyclohexane decomposition, was
      also studied over 1220-1700 K for 50 and 200 Torr using 2% and 3% 1-hexene in Kr.
      On heating, cyclohexane simply isomerizes to 1-hexene, and this then dissociates
      almost entirely by a more rapid C-C scission to allyl and n-propyl radicals. This
      two-step reaction results in an initial small density gradient from the slight
      endothermicity of the isomerization. The gradient then rises strongly as the
      product 1-hexene dissociates. For the lower temperatures, this behavior is fully
      resolved here. For the higher pressures, 1-hexene decomposition generates
      negative gradients (exothermic reaction) as the radicals formed begin to
      recombine. Cyclohexane also generates such gradients, but these are now much
      smaller because the radical pool is depleted by abstraction from the reactant. A
      complete mechanism for the 1-hexene decomposition and for that of cyclohexane
      involving 79 reactions and 30 species is used in the final modeling of the
      gradients. Rate constants and RRKM fit parameters for the initial reactions are
      provided for the entire range of conditions. The possibility of direct reaction
      to allyl and n-propyl radicals, without stabilization of the intermediate 1
      hexene, is examined down to pressures as low as 25 Torr, without a clear
      resolution of the issue. High-pressure limit rate constants from RRKM
      extrapolation are k(infinity)(c-C(6)H(12) --> 1-C(6)H(12)) = (8.76 x 10(17))
      exp((-91.94 kcal/mol)/RT) s(-1) (T = 1300-2000 K) and k(infinity)(1-C(6)H(12) -->
      (*)C(3)H(7) + (*)C(3)H(5)) = (1.46 x 10(16)) exp((-69.12 kcal/mol)/RT) s(-1) (T =
      1200-1700 K). This high-pressure rate for cyclohexane is entirely consistent with
      the notion that the isomerization involves initial C-C fission to a diradical.
      These extrapolated high-pressure rates are in good agreement with much of the
      literature.

PMID- 19842682
TI  - Steroidal sapogenins and glycosides from the rhizomes of Dioscorea bulbifera.
AB  - Four new steroidal sapogenins (1-4), named diosbulbisins A-D, two new spirostane
      glycosides, diosbulbisides A (5) and B (6), one new cholestane glycoside,
      diosbulbiside C (7), and the known compounds 8-10 were isolated from rhizomes of
      Dioscorea bulbifera. Their structures were elucidated by 1D and 2D NMR
      techniques, HRFTMS, and chemical methods. The unusual furospirostanol sapogenin
      skeletons, as found in compounds 3 and 4, are reported in the family
      Dioscoreaceae for the first time. Cytotoxicity of compounds 1-10 was evaluated
      using two human hepatocellular carcinoma cell lines (Bel-7402 and SMMC7721).

PMID- 19842683
TI  - Conformational changes of lipids in bilayers at the dynamical transition near 200
      K seen by Raman scattering.
AB  - Dynamical transition in biomolecules (proteins, membranes, etc.) is the
      phenomenon of increase of mean square atomic displacements, when temperature
      increases above 180-230 K. This increase is seen in neutron scattering and is
      ascribed to the increase of anharmonical motion of hydrogen atoms in
      biomolecules. In this work, Raman scattering study was performed for model
      synthetic membranes of dipalmitoylphosphatidylcholine in the spectral range of C
      C vibrations (1050-1150 cm(-1)). It was demonstrated that dynamical transition is
      accompanied by appearance of newly achievable conformations of the lipid tails.
      In particular, the portion of the all-trans conformations decreases above the
      temperature of the dynamical transition. The data are compared with simple
      theoretical models.

PMID- 19842684
TI  - Direct one-pot reductive amination of aldehydes with nitroarenes in a domino
      fashion: catalysis by gum-acacia-stabilized palladium nanoparticles.
AB  - This note describes the direct reductive amination of carbonyl compounds with
      nitroarenes using gum acacia-palladium nanoparticles, employing molecular
      hydrogen as the reductant. This methodology is found to be applicable to both
      aliphatic and aromatic aldehydes and a wide range of nitroarenes. The operational
      simplicity and the mild reaction conditions add to the value of this method as a
      practical alternative to the reductive amination of carbonyl compounds.

PMID- 19842685
TI  - Enhanced optical nonlinearity and improved transparency of inorganic-organic
      hybrid materials containing benzimidazole chromophores.
AB  - A series of novel inorganic-organic hybrid materials with benzimidazole
      chromophores covalently bonded into the inorganic silica network as pendants has
      been designed and synthesized via the wet chemistry routes. The measurement
      results of solvatochromic method and UV-vis spectra indicate that these
      benzimidazole chromophores exhibit higher microscopic optical nonlinearity
      compared with their analogues with benzene ring and without undesirable red-shift
      of the absorption band. After corona poling, the macroscopic nonlinear optical
      activity and poling alignment stability of the hybrid films were investigated by
      in situ second harmonic generation measurement. These hybrid films exhibit
      enhanced nonlinear optical coefficient from 25 to 54 pm/V with chromophore
      concentration varied, improved optical transparency (lambda(max) < 470 nm), as
      well as excellent polar orientation stability at 160 degrees C.

PMID- 19842686
TI  - Laetirobin from the parasitic growth of Laetiporus sulphureus on Robinia
      pseudoacacia.
AB  - (+/-)-Laetirobin (1) was isolated as a cytostatic lead from Laetiporus sulphureus
      growing parasitically on the black locust tree, Robinia pseudoacacia, by virtue
      of a reverse-immunoaffinity system. Using an LC/MS procedure, milligram
      quantities of (+/-)-laetirobin (1) were obtained, and the structure of 1 was
      elucidated by X-ray crystallography and confirmed by NMR spectroscopy.
      Preliminary cellular studies indicated that (+/-)-laetirobin (1) rapidly enters
      in tumor cells, blocks cell division at a late stage of mitosis, and invokes
      apoptosis.

PMID- 19842687
TI  - Synthesis of substituted imidazo[1,5-a]pyrazines via mono-, di-, and directed
      remote metalation strategies.
AB  - Imidazo[1,5-a]pyrazines 1 undergo regioselective C3-metalation and C5/C3
      dimetalation to afford a range of functionalized derivatives 2a-2g (Table 1 ),
      and 4a-4d (Table 2 ). Under similar conditions, the C3-methyl derivatives 2a and
      5 undergo surprising regioselective C5-deprotonation to afford, after
      electrophile quench, products 4b and 6a-6p (Table 3 ), results that are
      rationalized by quantum mechanical calculations. Benzamide 7b, obtained from such
      metalation chemistry followed by Suzuki cross coupling, undergoes directed remote
      metalation-cyclization to afford 8, representing the hitherto unknown
      triazadibenzo[cd,f]azulen-7(6H)-one tricyclic ring system.

PMID- 19842688
TI  - Oxidative amination of heteroaromatic zinc reagents mediated by PhI(OAc)(2).
AB  - The oxidative amination of functionalized heterocycles has been achieved by using
      readily available heterocyclic zinc reagents and lithium amides. PhI(OAc)(2)
      proved to be a suitable reagent for this oxidative amination.

PMID- 19842689
TI  - A one-pot approach to neoglycopeptides using orthogonal native chemical ligation
      and click chemistry.
AB  - The powerful combination of native chemical ligation and click chemistry has been
      used to affect a one-pot synthesis of neoglycopeptides from propargyl-containing
      peptides using GalNAc-N(3) as the glycan component. A versatile chemical toolkit
      for the fully convergent synthesis of neoglycoproteins using click chemistry,
      native chemical ligation, and kinetically controlled ligation is thus
      demonstrated.

PMID- 19842690
TI  - Junctions in axial III-V heterostructure nanowires obtained via an interchange of
      group III elements.
AB  - We present an investigation of the morphology and composition of novel types of
      axial nanowire heterostructures where Ga(x)In(1-x)As is used as barrier material
      in InAs nanowires. Using aberration-corrected scanning transmission electron
      microscopy and energy dispersive X-ray analysis we demonstrate that it is
      possible to grow junctions by changing the group III elements, and we find that a
      substantial fraction of Ga can be incorporated in axial InAs/Ga(x)In(1-x)As/InAs,
      retaining straight nanowire configurations. We explain how the adatoms are
      transferred to the incorporation site at the growth interface via two different
      routes, (1) interface diffusion and (2) volume diffusion through the catalyst
      particle.

PMID- 19842691
TI  - Chaperon-mediated single molecular approach toward modulating Abeta peptide
      aggregation.
AB  - We report here a single molecular approach using chaperone-like molecular
      modulators for modulating the aggregation behavior of a vital analogue of beta
      amyloid peptide (Abeta) by using scanning tunneling microscopy. The molecular
      structures of the beta-sheets for Abeta33-42 peptide are revealed, which are keen
      to the aggregation of Abeta42 relating to Alzheimer's disease. It was identified
      that the introduction of chaperone-like modulators could regulate the assembling
      behavior of the peptide at molecular level. Furthermore, the modulators could
      also significantly accelerate the aggregation of the peptide in aqueous solution
      as revealed by light scattering studies. These observations of the molecular
      modulator effect in peptide assemblies could provide a novel approach toward
      modulating Abeta peptide aggregations.

PMID- 19842692
TI  - Tug-of-war in nanoparticles: competitive growth of Au on Au-Fe3O4 nanoparticles.
AB  - Mechanical property of dumbbell-like Au-Fe(3)O(4) nanoparticles (NPs) is
      investigated from a synthetic point of view by overgrowing Au(2) on the Au(1)
      Fe(3)O(4) NPs. The competitive growth of Au(2) on the preformed Au(1)-Fe(3)O(4)
      NPs induced an interesting "tug-of-war" between Au(2) and Fe(3)O(4) in the formed
      Au(2)-Au(1)-Fe(3)O(4) ternary nanostructure. An interpretation of the observed
      phenomena is proposed based on a mechanical analysis of the stress and strain
      distribution across the nanoparticle, which is further verified by control
      experiments with particle size tuned.

PMID- 19842693
TI  - Epitaxially driven formation of intricate supported gold nanostructures on a
      lattice-matched oxide substrate.
AB  - A new class of gold nanostructures has been fabricated on the (100), (111), and
      (110) surfaces of lattice-matched MgAl(2)O(4) substrates. The nanostructures were
      fabricated through a synthesis route where a thin gold film dewets, liquefies,
      and then slowly self-assembles. The supported nanostructures are intricately
      shaped, crystalline, and epitaxially aligned. Simulations based on a continuum
      elastic theory indicate that the self-assembly is driven by strained epitaxy and
      minimization of the surface free energy.

PMID- 19842694
TI  - Bohmian total potential view to quantum effects III. Tunnelling in phase space.
AB  - The tunnel effect in one-dimensional collision problems is analyzed in terms of
      numerical wavepacket time propagations, in position, momentum, and phase space
      representations of the problem. Bohm's total potential is used to provide a
      classical-like description of tunnelling quantum dynamics, under a time- and
      density-dependent potential. Wigner, Husimi, as well as Bohm phase space
      distributions are used in the present study, with their relative performances for
      the present problem having been analyzed.

PMID- 19842695
TI  - Chiral sensing using a complementary metal-oxide semiconductor-integrated three
      transducer microsensor system.
AB  - Different chiral cyclodextrin derivatives were dissolved in a polysiloxane matrix
      and have been used as sensitive coatings on a three-transducer microsystem
      including a calorimetric, a mass-sensitive, and a capacitive chemical sensor.
      Upon exposure to chiral analytes, such as methyl lactate and methyl-2
      chloropropionate, all three transducers showed distinct chiral discrimination of
      these analytes. The signals were found to constitute a convolution of sorption
      thermodynamics and transducer-specific contributions, which included, in the case
      of the capacitive sensor, molecular orientation effects so that even opposite
      sign signals for the two enantiomers resulted. The sensor response curves of all
      three transducers could be explained and fitted by applying a model that
      essentially implies the superposition of a Langmuir isotherm representing
      specific interactions, predominant at low concentrations, and a Henry isotherm
      for nonspecific physisorption. The results disclosed here show that, on the one
      hand, sensor techniques can be used to reveal details of enantioselective analyte
      receptor or analyte-matrix interactions and that, on the other hand, sensors may
      provide an even more pronounced chiral discrimination ("discrimination
      enhancement") with respect to sorption-thermodynamics-determined gas
      chromatography as a consequence of the transducer-specific signal contributions.

PMID- 19842696
TI  - Enhanced hydrogen adsorptivity of single-wall carbon nanotube bundles by one-step
      c60-pillaring method.
AB  - Single-wall carbon nanotube (SWCNT) bundles were pillared by fullerene (C60) by
      the cosonication of C60 and SWCNT in toluene to utilize the interstitial pores
      for hydrogen storage. C60-pillared SWCNTs were confirmed by the shift in the X
      ray diffraction peak and the expanded hexagonal and distorted tetragonal bundles
      revealed by high-resolution transmission electron microscopy. The H2 adsorptivity
      of the C60-pillared SWCNT bundles was twice that of the original SWCNT bundles,
      indicating a design route for SWCNT hydrogen storage.

PMID- 19842697
TI  - Discrete cyclic porphyrin arrays as artificial light-harvesting antenna.
AB  - The importance of photosynthesis has driven researchers to seek ways to mimic its
      fundamental features in simplified systems. The absorption of a photon by light
      harvesting (antenna) complexes made up of a large number of protein-embedded
      pigments initiates photosynthesis. Subsequently the many pigments within the
      antenna system shuttle that photon via an efficient excitation energy transfer
      (EET) until it encounters a reaction center. Since the 1995 discovery of the
      circularly arranged chromophoric assemblies in the crystal structure of light
      harvesting antenna complex LH2 of purple bacteria Rps. Acidophila, many designs
      of light-harvesting antenna systems have focused on cyclic porphyrin wheels that
      allow for efficient EET. In this Account, we review recent research in our
      laboratories in the synthesis of covalently and noncovalently linked discrete
      cyclic porphyrin arrays as models of the photosynthetic light-harvesting antenna
      complexes. On the basis of the silver(I)-promoted oxidative coupling strategy, we
      have prepared a series of extremely long yet discrete meso-meso-linked porphyrin
      arrays and covalently linked large porphyrin rings. We examined the photophysical
      properties of these molecules using steady-state absorption, fluorescence,
      fluorescence lifetime, fluorescence anisotropy decay, and transient absorption
      measurements. Both the pump-power dependence on the femtosecond transient
      absorption and the transient absorption anisotropy decay profiles are directly
      related to the EET processes within the porphyrin rings. Within these structures,
      the exciton-exciton annihilation time and the polarization anisotropy rise time
      are well-described in terms of the Forster-type incoherent energy hopping model.
      In noncoordinating solvents such as CHCl(3), meso-pyridine-appended zinc(II)
      porphyrins and their meso-meso-linked dimers spontaneously assemble to form
      tetrameric porphyrin squares and porphyrin boxes, respectively. In the latter
      case, we have demonstrated the rigorous homochiral self-sorting process and
      efficient EET along these cyclic porphyrin arrays. The meso-cinchomeronimide
      appended zinc(II) porphyrin forms a cyclic trimer. We have also shown that the
      corresponding meso-meso-linked diporphyrins undergo high-fidelity self-sorting
      assembling to form discrete cyclic trimer, tetramer, and pentamer with large
      association constants through perfect discrimination of enantiomeric and
      conformational differences of the meso-cinchomeronimide substituents.
      Collectively, these studies of covalently and noncovalently linked discrete
      cyclic porphyrin arrays aid in the understanding of the structural requirements
      for such very fast EET in natural light-harvesting complexes.

PMID- 19842698
TI  - Multiroute synthesis of porous anionic frameworks and size-tunable extraframework
      organic cation-controlled gas sorption properties.
AB  - Under diverse and dramatically different chemical environments, including organic
      solvents, an ionic liquid, and a deep eutectic solvent, a series of porous
      anionic framework materials that contain size-tunable, ion-exchangeable
      extraframework organic cations have been prepared. Even though a large fraction
      of the pore space is occupied with charge-balancing cations, some of these
      materials exhibit a very high gas uptake capacity (e.g., 70.6 cm(3)/g for CO(2)
      at 1 atm and 273 K), suggesting that the charged anionic framework and
      extraframework cations may help to enhance the gas adsorption.

PMID- 19842699
TI  - Triple-bond reactivity of an AsP complex intermediate: synthesis stemming from
      molecular arsenic, As(4).
AB  - While P(4) is the stable molecular form of phosphorus, a recent study illustrated
      the possibility of P(2) generation for reactions in organic media under mild
      conditions. The heavier group 15 element arsenic can exist as As(4) molecules,
      but As(4) cannot be stored as a pure substance because it is both light-sensitive
      and reverts thermally to its stable, metallic gray form. Herein we report As(4)
      activation giving rise to a mu-As(2) diniobium complex, serving in turn as
      precursor to a terminal arsenide anion complex of niobium. Functionalization of
      the latter provides the new AsPNMes* ligand, which when complexed with tungsten
      pentacarbonyl elicits extrusion of the (AsP)W(CO)(5) molecule as a reactive
      intermediate. Trapping reactions of the latter with organic dienes are found to
      furnish double Diels-Alder adducts in which the AsP unit is embedded in a
      polycyclic organic framework. Thermal generation of (AsP)W(CO)(5) in the presence
      of the neutral terminal phosphide complex P identical withMo(N[(i)Pr]Ar)(3) leads
      to the cyclo-AsP(2) complex (OC)(5)W(cyclo-AsP(2))Mo(N[(i)Pr]Ar)(3). The
      (AsP)W(CO)(5) trapping products were crystallized and characterized by X-ray
      diffraction methods, and computational methods were applied for analysis of the
      As-As and As-P bonds in the complexes.

PMID- 19842700
TI  - An N,N'-diamidocarbene: studies in C-H insertion, reversible carbonylation, and
      transition-metal coordination chemistry.
AB  - Treatment of dimethylmalonyl dichloride with N,N'-bis(2,6-diisopropylphenyl)-N
      trimethylsilylformamidine followed by trimethylsilyl triflate (TMS.OTf) afforded
      the pyrimidinium salt [1H][OTf] in >99% yield. Subsequent deprotonation of this
      salt led to the formation of the corresponding free N-heterocyclic carbene (NHC)
      1. Exhibiting a reactivity profile that is characteristic of traditional
      electrophilic carbenes, 1 was found to insert into a tertiary C-H bond and
      reversibly fix carbon monoxide (CO) under mild conditions to afford the first
      example of a diamidoketene. Remarkably, the aforementioned carbonylation reaction
      was found to be thermally reversible (K(eq) = 2.62 M(-1) at 30 degrees C; DeltaH
      degrees = -35.33 kJ mol(-1) and DeltaS degrees = -109.5 J mol(-1) K(-1)). NHC 1
      also displayed nucleophilic characteristics. Treatment of 1 with [Ir(COD)Cl](2)
      (COD = 1,5-cyclooctadiene) afforded 1-[Ir(COD)Cl], a complex with bond lengths
      and angles that were in accord with known NHC analogues. Treatment of 1
      [Ir(COD)Cl] with CO afforded the carbonyl complex 1-[Ir(CO)(2)Cl]. IR studies of
      this complex revealed a Tolman Electronic Parameter of 2057 cm(-1), a value
      similar to those for analogous metal complexes containing tricyclohexylphosphine.

PMID- 19842701
TI  - Atomistic screening mechanism of ferroelectric surfaces: an in situ study of the
      polar phase in ultrathin BaTiO3 films exposed to H2O.
AB  - The polarization screening mechanism and ferroelectric phase stability of
      ultrathin BaTiO(3) films exposed to water molecules is determined by first
      principles theory and in situ experiment. Surface crystallography data from
      electron diffraction combined with density functional theory calculations
      demonstrate that small water vapor exposures do not affect surface structure or
      polarization. Large exposures result in surface hydroxylation and rippling,
      formation of surface oxygen vacancies, and reversal of the polarization
      direction. Understanding interplay between ferroelectric phase stability,
      screening, and atomistic processes at surfaces is a key to control low
      dimensional ferroelectricity.

PMID- 19842702
TI  - Distributed feedback lasing from a composite poly(phenylene vinylene)
      nanoparticle one-dimensional photonic crystal.
AB  - Nanoparticle one-dimensional photonic crystals exhibit intense, broadband
      reflectivity coupled with a unique mesoporosity. The latter property allows for
      infiltration of the one-dimensional photonic crystal with functional materials,
      such as emitting polymers, which in turn can lead to the fabrication of
      composites whereby the emitter's emission can be modulated by the photon density
      of states of the photonic crystal. We exploit this interaction in order to
      produce efficient distributed feedback lasing from a composite poly(phenylene
      vinylene)-infiltrated nanoparticle one-dimensional photonic crystal.

PMID- 19842703
TI  - Refractometric sensing using propagating versus localized surface plasmons: a
      direct comparison.
AB  - We present a direct experimental comparison between the refractive index sensing
      capabilities of localized surface plasmon resonances (LSPRs) in gold nanodisks
      and propagating surface plasmon resonances (SPRs) on 50 nm gold films. The
      comparison is made using identical experimental conditions, and for the same
      resonance wavelength, lambda(SP) congruent with 700 nm. Biosensing experiments
      with biotin-avidin coupling reveal that the two sensing platforms have very
      similar performance, despite a superior bulk refractive index sensing figure of
      merit for the SPR sensor. The results demonstrate that LSPR sensing based on
      simple transmission or reflection measurements is a highly competitive technique
      compared to the traditional SPR sensor.

PMID- 19842704
TI  - Stereospecific synthesis of alpha-substituted syn-alpha,beta-diamino acids by the
      diaza-Cope rearrangement.
AB  - Diaza-Cope rearrangement is used to make a variety of alpha-substituted syn
      alpha,beta-diamino acids. The rearrangement takes place with complete transfer of
      stereochemical integrity (>97% de and >98% ee) giving only one of four possible
      stereoisomers as determined by X-ray crystallography, (1)H NMR, and chiral HPLC.
      The observed stereospecificity can be explained in terms of DFT computation. This
      represents the first 1,4-diaza-Cope rearrangement with a ketone.

PMID- 19842705
TI  - Asymmetric total synthesis of (-)-awajanomycin.
AB  - The first asymmetric total synthesis of the unnatural enantiomer of cytotoxic
      awajanomycin (1) is reported. The synthetic approach features first a convergent
      strategy using the cross-olefin metathesis reaction to link the lipid side chain
      2 and the piperidinone core structure 3. The second feature of the synthesis
      resides on the construction of segment 3 from the building block 5 via a three
      component tandem reaction on the mixed imide 12. Through this work, the
      stereochemistry at C-11 and the absolute configuration of awajanomycin were
      established as 3R,5R,6S,8S,11S.

PMID- 19842706
TI  - Molecular dynamics simulation of aerosol-OT reverse micelles.
AB  - Molecular dynamics simulations are performed for the reverse micelles (RMs)
      formed by the surfactant Aerosol-OT (AOT, sodium bis(2-ethylhexyl)sulfosuccinate)
      in isooctane. The appropriate simulation methodology is identified and applied to
      the study of the effect of RM size, as quantified by w0 = [H2O]/[AOT], on the
      structure of the reverse micelle. The radial and intrinsic density profiles, pair
      densities and pair orientations in the first solvation shell, and water-water
      hydrogen bonding profiles were constructed. On the basis of these various
      structural characteristics, we find that the organization of sodium ions,
      sulfonate headgroup, and water oxygen atoms at the surfactant interface is
      consistent with a pseudolattice structure for w0 = 2. An increase in the RM size
      leads to the disruption of this lattice, with more sodium ions dissociating from
      the sulfonate headgroup and an increase in the aqueous solvation of these two
      species. The water molecules exist primarily in the interior of the RM and
      exhibit bulklike properties only for w0 approximately 7.5. Some water molecules
      and sodium ions exist in the intersulfonate headgroup region and interact with
      the AOT carbonyl group.

PMID- 19842707
TI  - Solar cells based on junctions between colloidal PbSe nanocrystals and thin ZnO
      films.
AB  - We report a new type of excitonic solar cell based on planar heterojunctions
      between PbSe semiconductor nanocrystals and thin ZnO films. These solar cells
      generate large photocurrents and higher photovoltages compared to Schottky cells
      assembled with similar nanocrystal films. When illuminated with 100 mW/cm(2)
      simulated AM1.5 spectrum, these solar cells exhibit short-circuit currents
      between 12 and 15 mA/cm(2), open-circuit voltages up to 0.45 V, and a power
      conversion efficiency of 1.6%. The photovoltage depends on the size of the
      nanocrystals, increasing linearly with their effective band gap energy.

PMID- 19842708
TI  - Predicting the cis-trans dichloro configuration of group 15-16 chelated ruthenium
      olefin metathesis complexes: a DFT and experimental study.
AB  - Gradient-corrected (BP86) and hybrid (M06-L) density functional calculations were
      used to study the relative stability of cis and trans-dichloro X-chelated
      benzylidene ruthenium complexes (X = O, S, Se, N, P). Calculations in the gas
      phase differed from experimental results, predicting the trans-dichloro
      configuration as being more stable in every case. The addition of Poisson
      Boltzmann (PBF) continuum approximation (dichloromethane) corrected the
      disagreement and afforded energies consistent with experimental results. Novel N,
      Se, and P chelated ruthenium olefin metathesis complexes were synthesized to
      evaluate calculation predictions. These findings reinforce the importance of
      including solvent corrections in DFT calculations of ruthenium metathesis
      catalysts and predict that stronger sigma donors as chelating atoms tend to
      electronically promote the unusual and less active cis-dichloro configuration.

PMID- 19842709
TI  - Mechanistic studies on a dipeptide-promoted asymmetric cyclopropanation of
      unfunctionalized olefins.
AB  - This paper describes mechanistic studies on a dipeptide-promoted asymmetric
      cyclopropanation system for unfunctionalized olefins. Zinc species generated from
      the deprotonation of the N-H of the dipeptide ligand have been investigated by
      NMR and X-ray structure studies and are likely to be responsible for asymmetric
      cyclopropanation. ZnI(2) plays an important role in promoting the reaction.

PMID- 19842710
TI  - RED: a set of molecular descriptors based on Renyi entropy.
AB  - New molecular descriptors, RED (Renyi entropy descriptors), based on the
      generalized entropies introduced by Renyi are presented. Topological descriptors
      based on molecular features have proven to be useful for describing molecular
      profiles. Renyi entropy is used as a variability measure to contract a feature
      pair distribution composing the descriptor vector. The performance of RED
      descriptors was tested for the analysis of different sets of molecular distances,
      virtual screening, and pharmacological profiling. A free parameter of the Renyi
      entropy has been optimized for all the considered applications.

PMID- 19842711
TI  - Betaglycan has two independent domains required for high affinity TGF-beta
      binding: proteolytic cleavage separates the domains and inactivates the
      neutralizing activity of the soluble receptor.
AB  - Betaglycan is a coreceptor for members of the transforming growth factor beta
      (TGF-beta) superfamily. Mutagenesis has identified two ligand binding regions,
      one at the membrane-distal and the other at the membrane-proximal half of the
      betaglycan ectodomain. Here we show that partial plasmin digestion of soluble
      betaglycan produces two proteolysis-resistant fragments of 45 and 55 kDa,
      consistent with the predicted secondary structure, which indicates an intervening
      nonstructured linker region separating the highly structured N- and C-terminal
      domains. Amino terminal sequencing indicates that the 45 and 55 kDa fragments
      correspond, respectively, to the membrane-distal and -proximal regions. Plasmin
      treatment of membrane betaglycan results in the production of equivalent
      proteolysis-resistant fragments. The 45 and 55 kDa fragments, as well as their
      recombinant soluble counterparts, Sol Delta10 and Sol Delta11, bind TGF-beta, but
      nonetheless, compared to intact soluble betaglycan, have a severely diminished
      ability to block TGF-beta activity. Surface plasmon resonance (SPR) analysis
      indicates that soluble betaglycan has K(d)'s in the low nanomolar range for the
      three TGF-beta isoforms, while those for Sol Delta10 and Sol Delta11 are 1-2
      orders of magnitude higher. SPR analysis further shows that the K(d)'s of Sol
      Delta11 are not changed in the presence of Sol Delta10, indicating that the high
      affinity of soluble betaglycan is a consequence of tethering the domains
      together. Overall, these results suggest that betaglycan ectodomain exhibits a
      bilobular structure in which each lobule folds independently and binds TGF-beta
      through distinct nonoverlapping interfaces and that linker modification may be an
      approach to improve soluble betaglycan's TGF-beta neutralizing activity.

PMID- 19842712
TI  - Reconstitution of Gloeobacter violaceus rhodopsin with a light-harvesting
      carotenoid antenna.
AB  - We show that salinixanthin, the light-harvesting carotenoid antenna of
      xanthorhodopsin, can be reconstituted into the retinal protein from Gloeobacter
      violaceus expressed in Escherichia coli. Reconstitution of gloeobacter rhodopsin
      with the carotenoid is accompanied by characteristic absorption changes and the
      appearance of CD bands similar to those observed for xanthorhodopsin that
      indicate immobilization and twist of the carotenoid in the binding site. As in
      xanthorhodopsin, the carotenoid functions as a light-harvesting antenna. The
      excitation spectrum for retinal fluorescence emission shows that ca. 36% of the
      energy absorbed by the carotenoid is transferred to the retinal. From excitation
      anisotropy, we calculate the angle between the two chromophores as being ca. 50
      degrees , similar to that in xanthorhodopsin. The results indicate that
      gloeobacter rhodopsin binds salinixanthin in a manner similar to that of
      xanthorhodopsin and suggest that it might bind a carotenoid also in vivo. In the
      crystallographic structure of xanthorhodopsin, the conjugated chain of the
      carotenoid lies on the surface of helices E and F, and the 4-keto ring is
      immersed in the protein at van der Waals distance from the ionone ring of the
      retinal. The 4-keto ring is in the space occupied by a tryptophan in
      bacteriorhodopsin, which is replaced by the smaller glycine in xanthorhodopsin
      and gloeobacter rhodopsin. Specific binding of the carotenoid and its light
      harvesting function are eliminated by a single mutation of the gloeobacter
      protein that replaces this glycine with a tryptophan. This indicates that the 4
      keto ring is critically involved in carotenoid binding and suggests that a number
      of other recently identified retinal proteins, from a diverse group of organisms,
      could also contain carotenoid antenna since they carry the homologous glycine
      near the retinal.

PMID- 19842713
TI  - Coupling of the distal hydrogen bond network to the exogenous ligand in substrate
      bound, resting state human heme oxygenase.
AB  - Mammalian heme oxygenase (HO) possesses catalytically implicated distal ordered
      water molecules within an extended H-bond network, with one of the ordered water
      molecules (#1) providing a bridge between the iron-coordinated ligand and the
      catalytically critical Asp140, that, in turn, serves as an acceptor for the Tyr58
      OH H-bond. The degree of H-bonding by the ligated water molecule and the coupling
      of this water molecule to the H-bond network are of current interest and are
      herein investigated by (1)H NMR. Two-dimensional NMR allowed sufficient
      assignments to provide both the H-bond strength and hyperfine shifts, the latter
      of which were used to quantify the magnetic anisotropy in both the ferric high
      spin aquo and low-spin hydroxo complexes. The anisotropy in the aquo complex
      indicates that the H-bond donation to water #1 is marginally stronger than in a
      bacterial HO, while the anisotropy for the hydroxo complex reveals a conventional
      (d(xz), d(yz))(1) ground state indicative of only moderate to weak H-bond
      acceptance by the ligated hydroxide. Mapping out the changes of the H-bond
      strengths in the network during the ligated water --> hydroxide conversion by
      correcting for the effects of magnetic anisotropy reveals a very substantial
      change in H-bond strength for Tyr58 OH and lesser effects on nearby H-bonds. The
      effect of pH on the H-bonding network in human HO is much larger and transmitted
      much further from the iron than in a pathogenic bacterial HO. The implications
      for the HO mechanism of the H-bond of Tyr58 to Asp140 are discussed.

PMID- 19842715
TI  - Glutathione transferases are structural and functional outliers in the
      thioredoxin fold.
AB  - Glutathione transferases (GSTs) are ubiquitous scavengers of toxic compounds that
      fall, structurally and functionally, within the thioredoxin fold suprafamily. The
      fundamental catalytic capability of GSTs is catalysis of the nucleophilic
      addition or substitution of glutathione at electrophilic centers in a wide range
      of small electrophilic compounds. While specific GSTs have been studied in
      detail, little else is known about the structural and functional relationships
      between different groupings of GSTs. Through a global analysis of sequence and
      structural similarity, it was determined that variation in the binding of
      glutathione between the two major subgroups of cytosolic (soluble) GSTs results
      in a different mode of glutathione activation. Additionally, the convergent
      features of glutathione binding between cytosolic GSTs and mitochondrial GST
      kappa are described. The identification of these structural and functional themes
      helps to illuminate some of the fundamental contributions of the thioredoxin fold
      to catalysis in the GSTs and clarify how the thioredoxin fold can be modified to
      enable new functions.

PMID- 19842714
TI  - The GTPase activity of Escherichia coli FtsZ determines the magnitude of the FtsZ
      polymer bundling by ZapA in vitro.
AB  - FtsZ polymerizes in a ring-like structure at mid cell to initiate cell division
      in Escherichia coli. The ring is stabilized by a number of proteins among which
      the widely conserved ZapA protein. Using antibodies against ZapA, we found
      surprisingly that the cellular concentration of ZapA is approximately equal to
      that of FtsZ. This raised the question of how the cell can prevent their
      interaction and thereby the premature stabilization of FtsZ protofilaments in
      nondividing cells. Therefore, we studied the FtsZ-ZapA interaction at the
      physiological pH of 7.5 instead of pH 6.5 (the optimal pH for FtsZ
      polymerization), under conditions that stimulate protofilament formation (5 mM
      MgCl(2)) and under conditions that stimulate and stabilize protofilaments (10 mM
      MgCl(2)). Using pelleting, light scattering, and GTPase assays, it was found that
      stabilization and bundling of FtsZ polymers by ZapA was inversely correlated to
      the GTPase activity of FtsZ. As GTP hydrolysis is the rate-limiting factor for
      depolymerization of FtsZ, we propose that ZapA will only enhance the
      cooperativity of polymer association during the transition from helical filament
      to mid cell ring and will not stabilize the short single protofilaments in the
      cytoplasm. All thus far published in vitro data on the interaction between FtsZ
      and ZapA have been obtained with His-ZapA. We found that in our case the presence
      of a His tag fused to ZapA prevented the protein to complement a DeltazapA strain
      in vivo and that it affected the interaction between FtsZ and ZapA in vitro.

PMID- 19842716
TI  - The thiolase reaction mechanism: the importance of Asn316 and His348 for
      stabilizing the enolate intermediate of the Claisen condensation.
AB  - The biosynthetic thiolase catalyzes a Claisen condensation reaction between
      acetyl-CoA and the enzyme acetylated at Cys89. Two oxyanion holes facilitate this
      catalysis: oxyanion hole I stabilizes the enolate intermediate generated from
      acetyl-CoA, whereas oxyanion hole II stabilizes the tetrahedral intermediate of
      the acetylated enzyme. The latter intermediate is formed when the alpha-carbanion
      of acetyl-CoA enolate reacts with the carbonyl carbon of acetyl-Cys89, after
      which C-C bond formation is completed. Oxyanion hole II is made of two main chain
      peptide NH groups, whereas oxyanion hole I is formed by a water molecule (Wat82)
      and NE2(His348). Wat82 is anchored in the active site by an optimal set of
      hydrogen bonding interactions, including a hydrogen bond to ND2(Asn316). Here,
      the importance of Asn316 and His348 for catalysis has been studied; in
      particular, the properties of the N316D, N316A, N316H, H348A, and H348N variants
      have been determined. For the N316D variant, no activity could be detected. For
      each of the remaining variants, the k(cat)/K(m) value for the Claisen
      condensation catalysis is reduced by a factor of several hundred, whereas the
      thiolytic degradation catalysis is much less affected. The crystal structures of
      the variants show that the structural changes in the active site are minimal. Our
      studies confirm that oxyanion hole I is critically important for the condensation
      catalysis. Removing either one of the hydrogen bond donors causes the loss of at
      least 3.4 kcal/mol of transition state stabilization. It appears that in the
      thiolytic degradation direction, oxyanion hole I is not involved in stabilizing
      the transition state of its rate limiting step. However, His348 has a dual role
      in the catalytic cycle, contributing to oxyanion hole I and activating Cys89. The
      analysis of the hydrogen bonding interactions in the very polar catalytic cavity
      shows the importance of two conserved water molecules, Wat82 and Wat49, for the
      formation of oxyanion hole I and for influencing the reactivity of the catalytic
      base, Cys378, respectively. Cys89, Asn316, and His348 form the CNH-catalytic
      triad of the thiolase superfamily. Our findings are also discussed in the context
      of the importance of this triad for the catalytic mechanism of other enzymes of
      the thiolase superfamily.

PMID- 19842717
TI  - The interaction of light and gravity on the transmission of Echinostoma caproni
      (Digenea: Echinostomatidae) cercariae to the second intermediate host,
      Biomphalaria glabrata (Gastropoda: Pulmonata).
AB  - The current experiments were designed to assess the interaction of light and
      gravity on the transmission of Echinostoma caproni cercariae to the second
      intermediate host, Biomphalaria glabrata. Transmission chambers were constructed
      of clear polyvinyl chloride pipe covered with a black sleeve to exclude light.
      Snails were constrained within the chamber to prevent movement, while permitting
      the cercariae to swim freely. A trial consisted of 2 infected B. glabrata
      shedding E. caproni cercariae placed at the center of the chamber with 5
      uninfected B. glabrata placed 10 cm above and below the shedding snails as
      sentinels. Three experiments, consisting of 12 trials each, were conducted under
      the following lighting conditions, i.e., above and below the transmission
      chamber, and in complete darkness. In all 3 experiments, the proportion of
      metacercariae was significantly higher in snails at the top of the chamber. The
      results suggest that a negative geotaxis is the primary factor in the initial
      dispersal of E. caproni cercariae. Coupling negative geotaxis and positive
      phototaxis (light from above) resulted in a significantly higher proportion of
      metacercariae in sentinel snails at the top of the transmission chamber when
      corrected for cercarial density. There was no significant difference in the
      proportion of metacercariae in snails at the top or bottom of the transmission
      chamber with light at the bottom of the chamber or in complete darkness.
      Cercariae of E. caproni only respond to light in context, i.e., from above, and
      ignore the light stimulus when it comes from an unexpected location (bottom of
      the water column). Significantly greater numbers of cercariae were released from
      shedding snails when light was present, suggesting that emergence of cercariae
      from B. glabrata is dependent on light regardless of the position of the light
      source.

PMID- 19842718
TI  - Endovascular treatment for chronic type B dissection: limitations of short stent
      grafts revealed at midterm follow-up.
AB  - PURPOSE: To examine the incidence of and the indications for re-intervention, as
      well as the changes in aortic morphology, in patients with chronic type B aortic
      dissection who underwent endovascular intervention for false lumen aneurysms.
      METHODS: A retrospective analysis was conducted of 10 patients (8 men; mean age
      63 years, range 45-79) who underwent stent-graft repair of aneurysmal false lumen
      expansion related to chronic type B aortic dissection at a median 16 months
      (range 2-71) from the initial diagnosis. All grafts had been oversized by 10%
      relative to the normal non-dissected aorta and were implanted to cover the
      primary entry tear. Follow-up computed tomography scans were analyzed to define
      changes in aortic morphology. RESULTS: Mean radiological follow-up was 56 months
      (median 64.5; range 19-86.5). There was no perioperative mortality or stroke; no
      cases of aortic rupture were recorded during follow-up. One patient suffered a
      procedure-related stroke with postoperative hemiparesis following re-intervention
      for proximal erosion 15 months after the initial treatment. In 6 of the 7 re
      interventions performed in 6 patients at a median 42 months after the index
      procedure, stent-graft extension was required to treat erosion of the dissection
      membrane that had resulted in endoleak with false lumen reperfusion. The extent
      of dissection, duration of follow-up, or length of aortic coverage was not
      predictive of the need for re-intervention during follow-up. At last follow-up,
      the mean false lumen diameter at the level of the stented aorta was significantly
      smaller than at baseline (11+/-15 versus 24+/-15 mm, p<0.01). This was associated
      with false lumen thrombosis at the level of the stent-graft in 9 of 10 cases,
      although 7 patients had persistent false lumen perfusion distal to the stent
      graft. CONCLUSION: Endovascular stent-graft treatment is effective therapy for
      chronic type B dissection patients with false lumen aneurysms. Erosion of the
      dissection membrane, causing proximal or distal endoleak, is the most common
      reason for re-intervention during midterm follow-up.

PMID- 19842720
TI  - Commentary: Population-based outcomes from administrative datasets: shedding
      light on the potential of endovascular repair to reduce mortality from ruptured
      AAA.

PMID- 19842719
TI  - Population-based outcomes following endovascular and open repair of ruptured
      abdominal aortic aneurysms.
AB  - PURPOSE: To evaluate national outcomes after endovascular and open surgical
      repair of ruptured abdominal aortic aneurysms (rAAA). METHODS: The Nationwide
      Inpatient Sample was interrogated to identify all repairs between 2000 and 2005
      for rAAA based on ICD-9 codes. In the study period, 2323 patients (1794 men;
      median age 75 years, range 45-98) with rAAAs had endovascular repair, while
      26,106 patients (20,311 men; median age 73 years, range 22-99) had an open
      procedure. Outcomes included in-hospital mortality, length of stay (LOS),
      complications, and hospitalization charge. A secondary analysis was performed to
      compare outcomes from low-, medium-, and high-volume institutions based on annual
      rAAA repair volume. RESULTS: Patients in the endovascular group were
      significantly older (p<0.05). Mortality was 41% overall: 33% and 41% for
      endovascular versus open repair, respectively (p<0.001). Mortality after
      endovascular repair was lower than open surgery for patients >or=70 years (36%
      versus 47%, p<0.001), but not for those <70 years (24% versus 30%, p = 0.15). LOS
      was shorter after endovascular repair (7 versus 9 days, p<0.001). Respiratory
      complications (8% versus 4%, p<0.05) and acute renal failure were more common
      following open repair (30% versus 23%, p<0.01). Costs were similar (endo $73,590
      versus open $67,287, p = 0.15). Mortality decreased as hospital surgical volume
      increased (low 44%, medium 39%, high 38%; p<0.001). Over time, endovascular
      repair utilization increased more rapidly at high-volume centers, and a lower
      mortality was seen with endovascular repair at high-volume compared to low-volume
      hospitals (22% versus 44%, p<0.001). Multivariate predictors of mortality were
      age, female gender, lower hospital surgical volume, open repair, and year of
      surgery. CONCLUSION: This population-based study found that mortality associated
      with rAAAs may be improved by the performance of endovascular repair, especially
      in older patients. Mortality after rAAA for both endovascular and open repairs
      was also lower at high-volume institutions.

PMID- 19842721
TI  - Safety of low-dose heparin for intracranial stent-assisted angioplasty: a
      randomized controlled pilot study.
AB  - PURPOSE: To access the safety of low-dose heparin in comparison to a high-dose
      regimen in patients undergoing intracranial stent-assisted angioplasty. METHODS:
      Sixty-four consecutive patients (53 men; mean age 54 years) undergoing stent
      assisted angioplasty of 70 intracranial arterial stenoses were randomized to
      receive either low-dose (2000-U bolus+500 U/h) or high-dose (3000-U bolus+800
      U/h) intravenous heparin during the procedure. The activated clotting time (ACT)
      was measured. The groups were compared for the following primary endpoints until
      hospital discharge: target lesion acute thrombosis, intracranial hemorrhage
      (ICH), and death. RESULTS: The overall angioplasty success rate was 93% (65/70
      lesions). Stents were placed in 94.7% (36/38) and 90.6% (29/32) of patients in
      the low-dose and high-dose groups, respectively (p = 0.65). The primary endpoint
      occurred in 6% (2/33) of patients in the low-dose group versus 16% (5/31) of
      patients in the high-dose group (p = 0.25). Two patients, 1 patient in each
      group, experienced acute target lesion thrombosis during the procedure (p = NS);
      ICH occurred in 5 patients: 1 in the low-dose group and 4 in high-dose group
      (3.0% versus 12.9%, p = 0.19). CONCLUSION: The use of a low-dose heparin regimen
      did not increase the incidence of target lesion thrombosis or ICH in this small
      pilot trial. Intraoperative low-dose heparin seems to be safe for patients
      undergoing intracranial stent-assisted angioplasty, but these data should be
      confirmed in a larger trial.

PMID- 19842722
TI  - Carotid artery angioplasty and stenting in patients with hostile anatomy: the
      multi-wire technique.
AB  - PURPOSE: To describe the multi-wire technique that facilitates cannulation of the
      carotid artery during angioplasty and stenting in patients with difficult neck
      anatomy. TECHNIQUE: When cannulation of the common carotid artery (CCA) was not
      effective with a 5-F diagnostic mammary artery catheter and standard single-wire
      technique, a 0.035-inch hydrophilic guidewire was advanced into the external
      carotid artery (ECA) with the aid of the road map technique and 6-mL injections
      of contrast. The catheter was exchanged for an 8-F MPA guiding catheter. If the
      first attempt to advance the guide catheter failed, an additional 2 or 3
      hydrophilic guidewires were placed within the ECA to advance the guiding catheter
      to the CCA, paving the way for carotid angioplasty. Of 140 patients referred to
      our center with hostile neck anatomies, this technique had been employed in 30
      (21%) patients (26 men; mean age 78+/-6 years): 15 (50%) had type III aortic
      arch, 7 (23%) had severe tortuosity of the CCA, and 8 (27%) had angulated
      takeoffs of the carotid or internal arteries. The 2-wire technique was used in 17
      patients, 3 wires in 9 patients, and 4 wires in 4 patients. Successful
      cannulation and correct stent deployment were achieved in all patients.
      Fluoroscopy time was longer in hostile neck patients compared with others (7.2+/
      3.1 versus 3.8+/-2.3 minutes, p<0.01). CONCLUSION: The multi-wire techniques
      appear to be a safe and effective method to aid cannulation and angioplasty of
      carotid arteries in patients with hostile neck anatomy.

PMID- 19842723
TI  - Impact of dynamic computed tomographic angiography on endograft sizing for
      endovascular aneurysm repair.
AB  - PURPOSE: To quantify dynamic changes in aortoiliac dimensions using dynamic
      electrocardiographically (ECG)-gated computed tomographic angiography (CTA) and
      to investigate any potential impact on preoperative endograft sizing in relation
      to observer variability. METHODS: Dynamic ECG-gated CTA was performed in 18
      patients with abdominal aortic aneurysms. Postprocessing resulted in 11 datasets
      per patient: 1 static CTA and 10 dynamic CTA series. Vessel diameter, length, and
      angulation were measured for all phases of the cardiac cycle. The differences
      between diastolic and systolic aneurysm dimensions were analyzed for significance
      using paired t tests. To assess intraobserver variability, 20 randomly selected
      datasets were analyzed twice. Intraobserver repeatability coefficients (RC) were
      calculated using Bland-Altman analysis. RESULTS: Mean aortic diameter at the
      proximal neck was 21.4+/-3.0 mm at diastole and 23.2+/-2.9 mm at systole, a mean
      increase of 1.8+/-0.4 mm (8.5%, p<0.01). The RC for the aortic diameter at the
      level of the proximal aneurysm neck was 1.9 mm (8.9%). At the distal sealing
      zones, the mean increase in diameter was 1.7+/-0.3 mm (14.1%, p<0.01) for the
      right and 1.8+/-0.5 mm (14.2%, p<0.01) for the left common iliac artery (CIA). At
      both distal sealing zones, the mean increase in CIA diameter exceeded the RC
      (10.0% for the right CIA and 12.6% for the left CIA). CONCLUSION: The observed
      changes in aneurysm dimension during the cardiac cycle are small and in the range
      of intraobserver variability, so dynamic changes in proximal aneurysm neck
      diameter and aneurysm length likely have little impact on preoperative endograft
      selection. However, changes in diameter at the distal sealing zones may be
      relevant to sizing, so distal oversizing of up to 20% should be considered to
      prevent distal type I endoleak.

PMID- 19842724
TI  - Commentary: Dynamics of the aorta and the influence on stent-graft sizing.

PMID- 19842725
TI  - Technical development and initial animal experience with a novel, uncovered, self
      expanding, highly flexible aortic stent with improved side branch access.
AB  - PURPOSE: To present a novel, uncovered, self-expanding aortic stent for use as a
      thoracoabdominal stent-graft extension to improve distal flow in aortic
      dissections complicated by malperfusion syndrome and to enhance the remodeling
      process in the abdominal aorta after thoracic endovascular aortic repair.
      METHODS: This aortic prosthesis is a laser cut, self-expanding nitinol stent that
      is designed to provide an optimal balance between radial support and flexibility
      to negotiate tortuous arterial anatomy. Undulating circumferential rings provide
      radial force, while flexibility is achieved through the shape and configuration
      of the longitudinal connectors that extend from the valley of one ring to the
      offset peak of the next ring. Delivery and deployment characteristics, in vivo
      flexibility of the stent, and side branch accessibility through the bare stent
      struts were evaluated in 4 anesthetized domestic swine weighing 68 to 73 kg.
      RESULTS: All 11 attempted stent implantations were successful in the 4 pigs using
      a retrograde transiliac access. The stents were positioned and deployed exactly
      at the intended target locations and conformed well to the aortic anatomy, even
      in the tortuous aortic arch, with no evidence of stent kinking or collapse.
      Overall, 21 major aortic side branches were intentionally covered with the bare
      stent struts; perfusion was not impaired in any branch vessel. Superselective
      catheterization of the side branches with coronary guiding catheters through the
      stent struts was possible for all vessels, as was side branch stenting in 3/3
      attempts. CONCLUSION: This initial feasibility study demonstrates the ability to
      deploy this novel self-expanding aortic stent in pigs. The high flexibility of
      the stent allowed conformability with tortuous aortic anatomy. Access to side
      branches overstented with bare stent struts was excellent. Clinical evaluation of
      the device is planned for the near future.

PMID- 19842726
TI  - Alternative hybrid reconstruction for bilateral common and internal iliac artery
      aneurysms associated with external iliac artery occlusion.
AB  - PURPOSE: To describe an alternative reconstruction for bilateral common (CIA) and
      internal (IIA) iliac artery aneurysms associated with external iliac artery (EIA)
      occlusion in a patient unfit for open surgery. CASE REPORT: A high-risk 81-year
      old man presented with contained rupture of a left CIA aneurysm in the presence
      of bilateral CIA and IIA aneurysms associated with complete occlusion of the left
      EIA and normal patency of both common femoral arteries. In an emergent procedure,
      the left EIA was recanalized subintimally, and the right IIA was embolized with a
      14-mm Amplatzer Plug. The main body of a standard Excluder endograft was deployed
      just distal to the origin of the left renal artery, and the ipsilateral leg was
      extended into the proximal right EIA. On the contralateral side, a short 10-mm
      diameter limb was inserted through a 12-F sheath and deployed in the CIA,
      proximal to the iliac bifurcation. Via a percutaneous left brachial artery
      access, 3 covered stents (9x59 mm, 10x59 mm, 10x59 mm) were deployed from the
      distal IIA to the endograft contralateral limb. A right-to-left femorofemoral
      crossover bypass graft concluded the operation. The patient was discharged on the
      5th postoperative day without complications; follow-up imaging at 6 months showed
      patency of the stent-graft and crossover bypass, with complete exclusion of the
      aneurysms and no evidence of endoleak. CONCLUSION: This case demonstrates an
      effective solution for complex aortoiliac lesions using commercially available
      devices, underlining how an accurate knowledge of alternative endovascular
      techniques and materials is crucial in the management of complex cases.

PMID- 19842727
TI  - Retrograde transpopliteal recanalization of chronic superficial femoral artery
      occlusion after failed re-entry during antegrade subintimal angioplasty.
AB  - PURPOSE: To evaluate the acute success and clinical impact of retrograde
      transpopliteal access for subintimal recanalization of superficial femoral artery
      (SFA) and proximal popliteal artery (PA) occlusions after failed attempts to re
      enter the true lumen in the antegrade femoral approach. METHODS: From 2002 to
      2007, 56 patients (43 men; mean age 68+/-9 years, range 43-87) with stable
      chronic peripheral artery disease (Rutherford category 2 to 5) were treated with
      antegrade subintimal angioplasty that could not be completed owing to re-entry
      failure. Mean occlusion length was 17+/-7 cm (range 4-32), including 13 TASC II A
      (23.2%), 10 TASC II B (17.8%), 16 TASC II C (28.5%), and 17 TASC II D (30.3%)
      lesions. After re-entry to the true lumen failed in the antegrade approach,
      including predilation of the false channel, all patients were turned to a prone
      position, and a 5-F or 6-F sheath was placed into the mid segment of the PA under
      fluoroscopic guidance. Retrograde wire passage was attempted with a 0.035-inch
      hydrophilic guidewire. RESULTS: Fifty-five (98.2%) of 56 procedures were finished
      successfully with a residual stenosis of <30%; the 1 failure was due stent
      deformation within the occluded segment that could not be passed from either an
      antegrade or retrograde access. In all interventions, balloon angioplasty was
      performed; provisional stenting was done in 40 (71.4%). In 3 (5.3%) lesions,
      additional excimer laser atherectomy were performed. Six (10.7%) complications
      occurred, including 1 arteriovenous fistula from the PA to the popliteal vein and
      1 sealing device induced PA occlusion. The mean ankle-brachial index increased
      from 0.44+/-0.26 to 0.86+/-0.23. The restenosis rate after 12 months was 54.9%.
      CONCLUSION: Failed antegrade attempts to recanalize chronic total occlusions of
      the SFA and proximal PA can be salvaged using a retrograde popliteal access, with
      a low complication rate, as an alternative to using a re-entry device. However,
      durability of the intervention using current interventional tools is limited.

PMID- 19842728
TI  - Staged proximal deployment of the Zenith TX2 thoracic stent-graft: a novel
      technique to improve conformance to the aortic arch.
AB  - PURPOSE: To present a modification of the Zenith TX2 thoracic stent-graft that
      allows staged proximal deployment to improve apposition to the aortic wall.
      TECHNIQUE: Three standard Zenith TX2 thoracic stent-grafts and 3 modified
      versions were deployed in a glass model of the aortic arch. Deployment sequences
      were analyzed. In a patient with a 6-cm thoracic aortic aneurysm after a type B
      dissection, the modified Zenith TX2 thoracic stent-graft was deployed
      successfully and without complications; the proximal part of the stent-graft
      protruded less into the arch, significantly improving wall apposition.
      CONCLUSION: Staged proximal deployment with a modified Zenith TX2 thoracic stent
      graft can improve orientation and wall apposition of the first Z stent. A better
      proximal apposition may prevent early and late stent-graft complications.

PMID- 19842729
TI  - Commentary: Stent-graft conformity to the arch knuckle: hugging the lesser
      curvature re-visited.

PMID- 19842730
TI  - Subintimal angioplasty for below-the-ankle arterial occlusions in diabetic
      patients with chronic critical limb ischemia.
AB  - PURPOSE: To assess the feasibility and efficacy of subintimal angioplasty (SA) in
      the treatment of below-the-ankle arterial occlusion in diabetic patients with
      chronic critical limb ischemia (CLI). METHODS: SA was applied in 37 diabetic
      patients (24 men; mean age 70.9+/-8.5 years, range 52-88) with chronic CLI and
      occlusive disease of the dorsalis pedis artery (DPA) and/or plantar artery (PA)
      but were poor candidates for intraluminal angioplasty or bypass surgery. Tissue
      loss was present in 31 (54.4%) of 57 afflicted limbs, and rest pain was reported
      in 51 (89.5%) limbs. SA was performed to create continuous arterial flow to the
      foot for limb salvage. The clinical symptoms, DPA or PA pulse volume scores, and
      ankle-brachial index (ABI) were compared before and after SA. Wound healing,
      amputation, and restenosis of target vessels were also evaluated at follow-up.
      Kaplan-Meier curves were constructed to evaluate limb salvage, survival, and
      freedom from amputation. RESULTS: Below-the-ankle SA was performed successfully
      in 55 (83.3%) of 66 arteries in 57 limbs. Median pulse volume scores and ABIs
      were 0.33+/-0.55 and 0.31+/-0.19 before SA and 2.04+/-1.05 and 0.80+/-0.14 after
      SA, respectively (p<0.0001 for both). The 30-day mortality was 2.7%. Median
      follow-up was 9.1+/-6.1 months (range 1-18). Major complications occurred in 1
      (2.7%) patient and minor complications in 3 (8.1%). Twelve months after SA,
      Kaplan-Meier analysis showed that the limb salvage rate was 94.6%, the freedom
      from amputation was 89.2%, and the survival rate was 97.3%. CONCLUSION: SA of the
      dorsalis pedis artery and/or plantar artery is a useful technique for lower limb
      salvage in diabetic patients with chronic CLI who are not candidates for bypass
      surgery.

PMID- 19842731
TI  - Commentary: Below-the-knee/ankle revascularization: tools of the trade.

PMID- 19842732
TI  - Commentary: Below-the-ankle subintimal angioplasty: how far can we push this
      application for lower limb preservation in diabetic patients?

PMID- 19842733
TI  - Outcomes of endovascular and open treatment for chronic mesenteric ischemia.
AB  - PURPOSE: To measure contemporary practice patterns and compare outcomes of open
      and endovascular repair for chronic mesenteric ischemia (CMI). METHODS: The New
      York State Health Department Statewide Planning and Research Cooperative System
      database was queried for the ICD-9-CM codes for CMI for the years 2000 to 2006.
      In this time period, 6549 patients were evaluated for CMI in New York State. Of
      these patients, 666 received an intervention and underwent either open (n = 280)
      or endovascular (n = 347) repair; 39 patients underwent both treatments and were
      excluded. Trends in operative management and short-term outcomes were analyzed.
      RESULTS: Over the 7-year study period, there was a steady increase in the number
      of endovascular procedures from 28% in 2000 to 75% in 2006. The overall mortality
      rate for the 7-year period was significantly lower for endovascular versus open
      repair (11.0% versus 20.4%, respectively; p = 0.0011). Endovascular repair was
      associated with a significantly lower rate of mesenteric ischemic complications
      compared to open repair (6.92% versus 17.1%, respectively; p<0.0001). Moreover,
      compared with open surgery, endovascular repair resulted in significantly lower
      rates of cardiac, pulmonary, and infectious complications (p<0.05). Only 37% of
      patients having open repair were discharged home compared to 55% of patients
      treated with endovascular procedures (p<0.0001). CONCLUSION: The number of
      patients treated for CMI continues to increase and correlates with the increasing
      utilization of endovascular procedures. The patients undergoing endovascular
      treatment had fewer complications, lower in-hospital mortality, and a greater
      likelihood of being discharged home.

PMID- 19842734
TI  - In vivo deformation of the human abdominal aorta and common iliac arteries with
      hip and knee flexion: implications for the design of stent-grafts.
AB  - PURPOSE: To quantify in vivo deformations of the abdominal aorta and common iliac
      arteries (CIAs) caused by musculoskeletal motion. METHODS: Seven healthy subjects
      (age 34+/-11 years, range 24-50) were imaged in the supine and fetal positions
      (hip flexion angle 134.0 degrees +/-9.7 degrees ) using contrast-enhanced
      magnetic resonance angiography. Longitudinal strain, twisting, and curvature
      change of the infrarenal aorta and CIAs were computed. The angle between the left
      and right CIAs and translation of the arteries were also computed. RESULTS:
      Maximal hip flexion induced shortening (5.2%+/-4.6%), twisting (0.45+/-0.27
      degrees /mm), and curvature changes (0.015+/-0.007 mm(-1)) of the CIAs. The angle
      between the CIAs increased by 17.6 degrees +/-8.6 degrees . The iliac arteries
      moved predominantly in the superior direction relative to the aortic bifurcation,
      which would induce compression and bending, thus increasing curvature and angle
      between the CIAs. The abdominal aorta also exhibited shortening (2.9%+/-2.1%) and
      twisting (0.07+/-0.05 degrees /mm) deformation associated with the hip flexion.
      CONCLUSION: Although this study was limited to a few healthy young adults,
      musculoskeletal motion, specifically hip flexion, caused significant in vivo
      morphological changes (shortening, twisting, and bending) of the arteries.
      Predominant superior translation of the CIAs was observed, which suggests that
      preclinical testing of cyclic superior-inferior translational motion may aid in
      predicting stent-graft fractures. In turn, stent-graft design could be improved,
      decreasing overall stent-graft-related complications.

PMID- 19842735
TI  - Effectiveness and safety of endovascular aneurysm treatment in patients with
      vasculo-Behcet disease.
AB  - PURPOSE: To compare long-term outcomes of endovascular and surgical treatment of
      arterial aneurysms in patients with vasculo-Behcet disease (VBD). METHODS: The
      medical records of 912 patients with Behcet disease who were seen between May
      1995 and January 2007 were reviewed. Among them, 34 (3.7%) patients with 39 non
      cerebral aneurysmal lesions were diagnosed with VBD. Between February 1998 and
      November 2006, 16 VBD patients (14 men; mean age 39.2+/-9.2 years, range 25-63)
      were treated for 20 arterial aneurysms with an endovascular technique (stent
      graft and/or coil embolization). All patients received immunosuppressive therapy
      (prednisolone 60 mg/d) before endovascular therapy to induce remission. From
      February 1993 to January 2007, 8 arterial aneurysms in 7 patients (all men; mean
      age 33.0+/-7.9 years, range 25-51) were treated with surgical graft interposition
      over 31.5+/-23.2 months. RESULTS: The endovascular procedure was successful in
      all lesions. The mean follow-up was 47.6+/-41.8 months, during which 4
      complications in 3 patients (3/16, 18.8%) occurred (2 occluded stent-grafts and 2
      access site pseudoaneurysm). There were no deaths. The cumulative primary patency
      rate in the endovascular group was 89% at 24 months. In the 7 patients undergoing
      graft interposition for 8 arterial aneurysms, 3 (42.9%) events occurred in follow
      up: 2 recurrent pseudoaneurysms and 1 aneurysm-related death. CONCLUSION: In
      Behcet disease, aneurysm treatment is performed whenever possible because of the
      high risk of rupture. Endovascular treatment of arterial aneurysms was effective
      and safe, with an acceptable vascular complication rate and excellent patency of
      the treated site.

PMID- 19842736
TI  - Commentary: Endovascular aneurysm treatment in patients with vasculo-Behcet
      disease.

PMID- 19842737
TI  - The Aorfix stent-graft to treat infrarenal abdominal aortic aneurysms with
      angulated necks and/or tortuous iliac arteries: midterm results.
AB  - PURPOSE: To present performance data on the use of the Aorfix stent-graft in
      patients with hostile infrarenal abdominal aortic aneurysm (AAA) anatomy.
      METHODS: A study protocol was designed to examine the safety and efficacy of the
      Aorfix endovascular stent-graft in AAA patients who had a proximal neck diameter
      between 18 and 30 mm, neck angulation between 60 degrees and 90 degrees , and/or
      severe iliac artery angulation/tortuosity. Between September 2005 and April 2009,
      20 men (mean age 72.4+/-7.7 years, range 55-89) were enrolled in the study. The
      mean AAA diameter was 61.8+/-14.9 mm (range 45.5-102). The mean angulation of the
      proximal neck was 61.9 degrees +/-16.5 degrees (range 30 degrees -90 degrees );
      in the iliac arteries, the angulation was 59.9 degrees +/-16.3 degrees (range 30
      degrees -85 degrees ) for the left and 60.9 degrees +/-17.6 degrees (range 28
      degrees -90 degrees ) on the right. Fourteen (70%) patients had >60 degrees
      proximal neck angulation. Outcome measures were analyzed using life-table
      analysis. RESULTS: The graft was successfully implanted in all but 1 patient
      (technical success 95%); failure to cannulate the contralateral iliac limb
      resulted in conversion to aortomonoiliac stent-graft placement. In 1 patient,
      bilateral renal artery stent rescue was performed due to severe procedure-related
      stenosis. Occlusion of an internal iliac artery was noted in 2 patients. Mean
      follow-up was 26.9 months (range 4.5-43.5). No aneurysm-related rupture or death
      occurred. Two endoleaks were observed: 1 type I without migration at 3 years and
      1 type II at 13 months. Freedom from any type of endoleak was 91.6% at 1 year and
      75.9% at 2 years. Freedom from any early or late intervention was 88.8% at 1 year
      and 76.0% at 2 years. Aneurysm sac shrinkage (>5 mm) was evident in 79% (11/14)
      of the cases reaching 12-month follow-up. CONCLUSION: The Aorfix device seems to
      be safe and reliable in purely complex infrarenal AAA anatomy, demonstrating good
      short and midterm clinical outcomes. Further larger or multicenter studies are
      needed to confirm the suitability of the Aorfix stent-graft in hostile infrarenal
      AAA anatomy.

PMID- 19842738
TI  - Initial experience with abdominal aneurysm repair using the E-vita abdominal
      stent-graft: a single-center study.
AB  - PURPOSE: To evaluate the feasibility and midterm results of a new stent-graft for
      infrarenal endovascular aneurysm repair (EVAR) in a non-selected population.
      METHODS: Nineteen consecutive patients (19 men; mean age 70 years, range 58-87)
      who presented within an 8-month period with abdominal aortic aneurysms (AAA)
      suitable for EVAR were treated with the new E-vita abdominal stent-graft. Most of
      the patients (13, 68%) were ASA grade 3 or higher; the maximum AAA diameter was
      57 mm (40-75), and hostile necks were present in a third and tortuous iliac
      arteries in half. Most of the cases (18, 95%) were elective; 1 was performed for
      a contained rupture. Seventeen procedures were primary implantations and 2 were
      secondary repairs of failing endografts. RESULTS: All stent-grafts were implanted
      at the intended position; no conversions to open surgery were necessary and no
      type I endoleak was noted. Fifteen bifurcated and 4 straight stent-grafts were
      implanted; the majority of the vascular accesses (29/35, 83%) were percutaneous.
      There was no 30-day mortality. In the mean 10-month follow-up (range 4-17), no
      stent fractures, migrations, or secondary endoleaks were noted. Aneurysm diameter
      was reduced in 8 (42%) and remained unchanged in 11 (58%) patients. One patient
      required open surgery at 1 year for thrombotic occlusion of the stent-graft. Two
      octogenarian patients died during follow-up. CONCLUSION: The E-vita abdominal
      stent-graft appears safe and effective in this initial midterm clinical
      experience. This device appears especially suitable to challenging aneurysm
      anatomy, such as severely angulated necks or tortuous and dilated iliac arteries.

PMID- 19842739
TI  - Propensity scores: method for matching on multiple variables in down syndrome
      research.
AB  - Confounding variables can affect the results from studies of children with Down
      syndrome and their families. Traditional methods for addressing confounders are
      often limited, providing control for only a few confounding variables. This study
      introduces propensity score matching to control for multiple confounding
      variables. Using Tennessee birth data as an example, newborns with Down syndrome
      were compared with a group of typically developing infants on birthweight. Three
      approaches to matching on confounders--non-matched, covariate matched, and
      propensity matched--were compared using 8 potential confounders. Fewer than half
      of the newborns with Down syndrome were matched using covariate matching, and the
      matched group was differed from the unmatched newborns. Using propensity scores,
      100% of newborns with Down syndrome could be matched to a group of comparison
      newborns, a decreased effect size was found on newborn birthweight, and group
      differences were not statistically significant.

PMID- 19842740
TI  - Perspectives on leadership in organizations providing services to people with
      disabilities: an exploratory study.
AB  - As leaders from the Baby Boomer generation prepare for retirement over the next
      decade, emerging leaders must be identified and supported in anticipation of a
      major organizational transition. Authentic leadership is a construct that informs
      the development of values-driven leaders who will bring organizations into the
      future, just as the previous generation of leaders oversaw the movement of
      services away from state institutions and into networks of community-based
      service delivery organizations. The purpose of this exploratory study was to
      examine executive and emerging leaders' opinions about the unique leadership
      values, skills, and challenges in organizations that serve individuals with
      intellectual and developmental disabilities. Themes of defining, developing, and
      sustaining leaders emerged from the data and are explored through an authentic
      leadership framework.

PMID- 19842741
TI  - Grammar and lexicon in individuals with autism: a quantitative analysis of a
      large Italian corpus.
AB  - Statistical and linguistic procedures were implemented to analyze a large corpus
      of texts written by 37 individuals with autism and 92 facilitators (without
      disabilities), producing written conversations by means of PCs. Such texts were
      compared and contrasted to identify the specific traits of the lexis of the group
      of individuals with autism and assess to what extent it differed from the lexis
      of the facilitators. The purpose of this research was to identify specific
      language features using statistical procedures to analyze contingency lexical
      tables that reported on the frequencies of words and grammatical categories in
      different subcorpora and among different writers. The results support the
      existence of lexis and distributional patterns of grammatical categories that are
      characteristic of the written production of individuals with autism and that are
      different from those of facilitators.

PMID- 19842742
TI  - Borderline intellectual functioning and the intellectual disability construct.

PMID- 19842743
TI  - Joe Arridy, "The happiest man who ever lived on death row".

PMID- 19842744
TI  - Invisible access needs of people with intellectual disabilities: a conceptual
      model of practice.

PMID- 19842745
TI  - The 10th anniversary of olmstead (1999): has it made a difference for people with
      developmental disabilities?

PMID- 19842748
TI  - The final word...

PMID- 19842749
TI  - Don't let common sense take a back seat to technology.

PMID- 19842750
TI  - Burden of proof... the certification debate continues.

PMID- 19842751
TI  - Auto industry eyes medical device manufacturing.

PMID- 19842752
TI  - Report urges development in Children's Health IT.

PMID- 19842753
TI  - Can your association survive the loss of a key leader?

PMID- 19842754
TI  - Biomed Roundup.

PMID- 19842755
TI  - TMC Corner.

PMID- 19842756
TI  - Inside AAMI.

PMID- 19842760
TI  - New diagnostic imaging devices automatically record radiation exposure.

PMID- 19842761
TI  - For the kids: managing medical equipment in children's hospitals.

PMID- 19842763
TI  - Executive uses clinical lessons in implementing new technology. Interview by
      BI&T.

PMID- 19842764
TI  - Advice to live by... the keys to countering stress.

PMID- 19842765
TI  - A tale of two orientation programs.

PMID- 19842766
TI  - Reducing downtime in oxygen concentrators.

PMID- 19842767
TI  - Sharpening the focus: medical imaging in children's hospitals. Interview by BI&T.

PMID- 19842768
TI  - Patient safety action group promotes proactive safety culture.

PMID- 19842769
TI  - Life safety: a team effort in hospitals.

PMID- 19842770
TI  - Integrating medical devices to clinical information systems.

PMID- 19842771
TI  - Electroencephalographs.

PMID- 19842772
TI  - Are your refrigerators safe? Solving airflow problems.

PMID- 19842773
TI  - Emergency management: the biomed's role in ensuring patient safety.

PMID- 19842774
TI  - Sterilizers: different repairs, different testing requirements.

PMID- 19842775
TI  - Q&A with the Joint Commission: new regulations spark questions, feedback.

PMID- 19842776
TI  - The global harmonization task force: what you need to know.

PMID- 19842777
TI  - Moist heat sterilization: new guidance for users, manufacturers.

PMID- 19842778
TI  - Safe and effective devices and instruments for use in the neonatal intensive care
      units: NICHD Workshop summary.
AB  - The neonatal intensive care unit (NICU) depends heavily on advanced biomedical
      devices for monitoring, diagnosis, and treatment. Developing safe and effective
      devices for use in the NICU requires collaborative research and testing efforts
      between the bioengineering and biomedical disciplines. However, no mechanism
      exists to match the needs of the clinical community and the efforts of the
      bioengineering community. To address this issue, in February 2009, the Eunice
      Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
      of the National Institutes of Health (NIH) invited a team of experts from diverse
      fields of biomedicine and bioengineering to participate in a workshop. The team
      reviewed and summarized bioinstrumentation needs and proposed a research agenda
      to develop safe and effective devices and instruments. The discussants addressed
      topics in cardiopulmonary, cerebrovascular, metabolic, and infectious conditions
      of the neonate. The authors provide a summary of the workshop discussions in this
      paper.

PMID- 19842779
TI  - What makes a good union?

PMID- 19842780
TI  - Personal characteristics and experiences of long-term allied health professionals
      in rural and northern British Columbia.
AB  - INTRODUCTION: Health sciences programs are being designed to attract students who
      are likely to stay and practice in rural and northern Canada. Consequently,
      student recruitment and screening are increasingly including assessment of
      suitability for rural practice. Although retention factors among rural physicians
      and nurses have been investigated, little is known about factors that contribute
      to the retention of other healthcare professionals who work in rural areas. The
      primary objective of this project was to identify the personal characteristics
      and experiences of allied health professionals who have worked long term in
      northern British Columbia (BC), Canada. METHODS: The study used a qualitative
      descriptive approach. Six speech language pathologists, four psychologists, four
      occupational therapists, eight social workers, and four physiotherapists
      practicing long term in northern BC were recruited, using a convenience sample
      and the snowball technique, to participate in semi-structured telephone
      interviews. The interviews were audiotaped and transcribed verbatim. A thematic
      content analysis identified the motivations for their decision to begin or stay
      working in northern communities, the reasons for choosing rural or northern
      education and key themes concerning personal characteristics and experiences. A
      process of member checking and an external audit validated the analysis and
      findings. RESULTS: There were two major themes for choosing rural and northern
      education. For some, selection of rural or northern training was based on
      accessibility to health education programs; all participants who chose rural and
      northern education had already decided that they were going to practice rurally.
      Generally, participants identified past positive experiences and rural background
      as influencing their practice location decision. Participants named the
      community's need for healthcare professionals, career advancement opportunities,
      welcoming employers, peer support, as well as promises of continuing education
      and interprofessional teamwork as key to their decision. Professional preferences
      for variety, challenges, and trying new aspects of the job such as teaching also
      impacted their decision. Also identified were individual factors and personal
      preferences such as the need for adventure, wilderness, and outdoor recreation,
      and community factors (eg people's friendliness and the slow pace). Such factors
      also influenced retention; however, retention was also affected by factors such
      as job satisfaction, and some community factors were only associated with
      retention. The analysis revealed a number of personal characteristics and
      experiences shared by long-term healthcare professionals, and that there is not
      one particular factor that determines duration of practice in rural and northern
      communities. CONCLUSION: The findings imply a combination of varying personal
      values impact the decision to come or stay in rural and northern communities.
      Personal characteristics and experiences help to shape these personal values.
      Over time and depending on stage of life, personal values change. Age and stage
      of life, rural background, and location of family members also have bearing on
      personal values, which in turn impact recruitment and retention. An explicit
      identification of values that have emerged out of personal characteristics and
      experiences may be useful in the selection of students for rural health education
      programs, as well as the recruitment and retention of healthcare professionals in
      rural and northern areas.

PMID- 19842781
TI  - Autism and aging: hardly out of the woods.
AB  - Leo Kanner first described autism in 1943, but it took the America Psychiatric
      Association almost 40 years to recognize it officially in 1980. It is one of five
      diverse pervasive developmental disorders grouped under the diagnostic category
      of autism spectrum disorders (ASD). Autism's core symptoms include socialization
      deficits, inability to understand and communicate with others, and restricted,
      repetitive behavioral patterns. Few children "outgrow it" or are cured. While
      good care and early intervention can help children develop the skills they need
      to deal with others in socially appropriate ways, clinicians usually see these
      same or similar behaviors in adults. ASD is associated with an array of problems
      including anxiety, depression, food allergies, and attention deficit
      hyperactivity disorders. Because the onset of autism occurs in early childhood,
      long-term care practitioners are more apt to encounter older adults who were
      misdiagnosed in childhood. When behavioral interventions are not fully effective,
      clinicians and families may look for medication. No medications are approved to
      treat autism's core symptoms. People with ASD have mental health disorders at
      rates higher than their peers, and these disorders can be treated. Long-term care
      practitioners need to prepare to see the people first diagnosed with autism in
      the 1980s who are now reaching old age with the need for long-term care
      facilities.

PMID- 19842782
TI  - Intravenous medications in long-term care: a wake-up call for pharmacists.
AB  - Many facilities are increasing the use of intravenous (IV) medications in an
      effort to care for patients with more complex health care needs. The number of IV
      medications also is increasing, and these products are helping keep patients in
      nursing facilities from being hospitalized. While some pharmacists have been
      hesitant to expand their expertise to include IV medications, it is essential
      that they do so to ensure the safe and cost-effective use of these therapies.

PMID- 19842783
TI  - The relationship between anticholinergic medications and Mini-Cog scores in older
      adults receiving home health care.
AB  - OBJECTIVES: To describe anticholinergic use patterns in older adult home health
      recipients and examine their relationship to evidence of cognitive impairment.
      DESIGN: Retrospective study. SETTING: A home health care agency in Eastern
      Washington state. PARTICIPANTS: Potential study subjects were 174 recipients of
      home health services between March 1, 2006, and October 1, 2006, who were 60
      years of age or older and had been screened for cognitive impairment by the Mini
      Cog assessment test. A random sample of 65 out of 75 patients who scored in the
      impaired range on the Mini-Cog and a random sample of 65 out of 99 patients who
      scored in the unimpaired range were included in the study. MAIN OUTCOME MEASURE:
      prevalence of anticholinergic medication use. RESULTS: The majority of
      participants (80.0%) were using a medication with anticholinergic effects;
      however, more participants were using weak anticholinergics (66.1%) than potent
      agents (33.8%). After controlling for age, caregiver presence, and marital
      status, participants who scored as cognitively impaired on the Mini-Cog were less
      likely to be taking a medication with anticholinergic properties (odds ratio
      0.34, 95% confidence interval 0.13-0.94). CONCLUSION: Although anticholinergic
      use was common in this older adult, home health population, the majority of
      participants were using medications with weak anticholinergic activity, as
      opposed to potent ones. Participants with cognitive impairment were less likely
      to be using any medication with anticholinergic properties.

PMID- 19842784
TI  - Cognitive decline after invasive intervention in cardiovascular disease: is it
      drug related?
AB  - OBJECTIVE: To identify drugs used to treat cardiovascular disease (CVD) after an
      invasive intervention that may adversely affect cognitive function. SETTING:
      Ambulatory care setting. PRACTICE DESCRIPTION: A pharmacy faculty member serves
      as an ambulatory care preceptor for students at a cardiac rehabilitation and
      wellness center on the campus of St. Joseph's Hospital, Atlanta, Georgia.
      Pharmacy services include patient case reviews, consultations, patient education,
      and therapeutic recommendations. PRACTICE INNOVATION: As part of the advanced
      practice experience, students are responsible for monitoring drug therapy
      regimens and conducting medication reconciliations. A literature review of
      primary sources and education databases was conducted to report cognitive adverse
      drug reactions associated with cardiac drugs in selective electronic tertiary
      sources. MAIN OUTCOMES: Documentation of cognitive dysfunction associated with
      drugs used to treat CVD. RESULTS: Drugs used to treat CVD may be associated with
      adverse drug effects including short-term memory loss, amnesia, confusion,
      decreased mental acuity, and impaired concentration. CONCLUSION: Pharmacists
      providing consultation in the cardiac rehabilitation setting can provide insight
      into medications that can contribute to cognitive dysfunction.

PMID- 19842785
TI  - Influenza vaccine and the elderly.
AB  - Although some controversy exists about the necessity of the annual influenza
      vaccine in the elderly population, it has been established that the benefits
      outweigh the risks. Vaccinating elderly patients helps prevent influenza-related
      mortality, avoids debilitating complications, and even averts exacerbation of
      certain comorbidities including chronic obstructive pulmonary disease, asthma,
      and metabolic disorders such as diabetes. Even with all of its established
      benefits, barriers to access can prevent elderly individuals from receiving the
      vaccine. These barriers include a lack of education regarding the vaccine and a
      lack of vaccination enforcement by health care providers. As health care
      providers, it is our responsibility not only to treat disease, but also to
      prevent disease from occurring. The influenza vaccine is an easy and cost
      effective way to prevent infection from the virus and the serious complications
      that may accompany it which, in turn, helps improve patients' quality of life.

PMID- 19842786
TI  - Sticky fingers: dealing with employee theft.

PMID- 19842787
TI  - Retraction. Withdrawn: Severe ataxia with neuropathy in hereditary gelsolin
      amyloidosis.

PMID- 19842788
TI  - Life satisfaction, anxiety, depression and resilience across the life span of
      men.
AB  - OBJECTIVE: To determine (a) the relationship between life satisfaction, anxiety,
      depression and ageing in the male community and (b) to identify the impact of
      vulnerability factors, personal and social resources on life satisfaction and
      distress. DESIGN: A stratified random sample of the German male population (N =
      2144) was investigated by standardized questionnaires of life satisfaction
      (FLZ(M)), depression, anxiety (PHQ), resilience (RS-11) and self-esteem (RSS).
      RESULTS: No age-related change was found regarding overall life satisfaction.
      Satisfaction with health decreased in midlife (51-60 years), while the importance
      of health increased. Importance of and satisfaction with partnership and
      sexuality were only reduced in the oldest group (70+). Anxiety was highest around
      midlife (51-60 years), accompanied by reduced resilience and self-esteem. No
      clear age-related change was found regarding depression. Life satisfaction was
      strongly associated with resilience, lack of unemployment, the presence of a
      partnership, positive self-esteem, a good household income, the absence of
      anxiety and depression and living in the Eastern states. CONCLUSIONS: Personal
      and social resources and the absence of anxiety and depression are of crucial
      importance for the maintenance of life satisfaction in ageing men. There is also
      evidence for a crisis around midlife manifested by health concerns, anxiety and
      reduced resilience.

PMID- 19842789
TI  - Ovulation disturbances and mood across the menstrual cycles of healthy women.
AB  - We examined the cyclicity of negative mood relative to ovulation and ovulation
      disturbances in Menstrual Cycle Diary(c) data collected daily during a 1-year
      study of ovulation, exercise, and bone change. A validated quantitative basal
      temperature-based methodology was used to determine the onset of the luteal
      phase. 'Feeling depressed', 'feeling anxious', and 'feeling angry/frustrated'
      were scored on a scale of 0 (absent) to 4 (very intense). Mood scores were
      examined over two 15-day intervals centered on either ovulation/midpoint, or on
      the onset of flow. Data were available from 765 cycles of 62 healthy and
      initially ovulatory women with a mean age of 33.9 +/- 5.4 years. Of 739 cycles
      that could be classified, 532 (72%) were normally ovulatory, 185 (25%) were
      ovulatory with a short (<10 day) luteal phase, and 22 (3%) were anovulatory.
      Minor cyclic mood changes were present in both ovulatory and anovulatory
      menstrual cycles. In anovulatory cycles, mood tended to be more variable but less
      negative, with a time course that differed from that in ovulatory cycles. Mood
      scores did not differ based on luteal phase length or with hormone levels.
      Patterns and mechanisms of mood change in very symptomatic women appear to be
      essentially amplifications of normal experiences.

PMID- 19842790
TI  - Arm/shoulder problems in breast cancer survivors are associated with reduced
      health and poorer physical quality of life.
AB  - BACKGROUND: Except for lymphedema, the consequences of arm/shoulder problems
      (ASPs), at long-term in breast cancer survivors (BCSs) have hardly been studied.
      We examined demography, lifestyle, quality of life (QoL) and somatic morbidity in
      BCSs with and without ASPs. We also compared the associations of restricted
      shoulder abduction and lymphedema with QoL. METHODS: We used a cross-sectional
      case-control design. A sample of 256 BCSs all with lymph node metastases were
      examined at a mean of 4.1 (SD 0.9) years post-surgery. Based on objective
      examinations and self-rating the sample were separated into 81 BCSs (32%) with
      definite ASP (ASP+ group) and 175 (68%) with minimal or no ASP (ASP- group). The
      self-rating contained among other schedules the Short Form-36 (SF-36) and the
      Kwan's arm/shoulder problem scale (KAPS). RESULTS: In univariate analysis ASP+
      was associated with not being employed, having had mastectomy, longer follow-up
      time, radiotherapy to axilla, poorer self-rated health and physical condition,
      minimal physical activity, increased body mass index, regularly intake of
      analgesics, and poorer physical QoL. Multivariate analysis showed that
      mastectomy, longer follow-up time, minimal physical activity and poorer physical
      QoL were associated with belonging to ASP+ group. All domains of the SF-36 were
      significantly associated with having impaired shoulder abduction (> or = 25
      degrees difference) while none of the associations with lymphedema were
      significant. DISCUSSION: In BCSs, at four years after treatment, having ASP was
      associated with mastectomy, minimal physical activity and poorer physical QoL.
      Poor physical QoL is strongly associated with reduced shoulder abduction rather
      than with lymphedema.

PMID- 19842791
TI  - In-depth analysis of the origins of HIV type 1 subtype C in South America.
AB  - The South American HIV-1 epidemic is characterized by the co-circulation of
      subtype B and BF recombinant variants. Together with the B and BF genotypes, HIV
      1 subtype C (HIV-1C), F1, and several other recombinants have been reported. The
      epidemiological significance and immune correlates of these "non-B-non-BF"
      strains circulating in South America are still uncertain and therefore are
      increasingly attracting the interest of the scientific community. In this study,
      the South American HIV-1C epidemic was studied using new technologies for the
      phylogenetic analysis of large datasets. Our results indicate that there is a
      major clade encompassing most of the South American HIV-1C strains. These
      analyses also agreed that some strains do not group inside this major clade,
      suggesting that there could be HIV-1C sequences of different origins circulating
      in South America. Others have proposed different hypotheses about the origins of
      HIV-1C strains from South America. This study shows that an exact single origin
      cannot be determined, a fact that could be attributed to sampling problems,
      phylogenetic uncertainty, and the shortage of historical and epidemiological
      data. Currently, the reported data indicate that HIV-1C strains were introduced
      in Brazil and afterward spread to other regions of South America. By using
      character optimization on the obtained phylogenetic trees, we observed that
      Argentina could also be a point in which the HIV-1C epidemic entered South
      America.

PMID- 19842792
TI  - Changes in drug resistance patterns following the introduction of HIV type 1 non
      B subtypes in Spain.
AB  - Natural genetic variability at the pol gene may account for differences in drug
      susceptibility and selection of resistance patterns across HIV-1 clades. Spread
      of non-B subtypes along with changes in antiretroviral drug use may have modified
      drug resistance patterns in recent years. All HIV-1 clinical samples sent to a
      reference laboratory located in Madrid for drug resistance testing since January
      2000 were analyzed. The pol gene was sequenced and HIV-1 subtypes were assigned
      using the Stanford algorithm and phylogenetic analyses for non-B subtypes. Drug
      resistance mutations were recorded using the IAS-USA mutation list (April 2008).
      A total of 3034 specimens from 730 antiretroviral-naive individuals (92 with non
      B subtypes) and 1569 antiretroviral-experienced patients (97 with non-B subtypes)
      were examined. The prevalence of HIV-1 non-B subtypes in the study period
      increased from 4.4% (2000-2003) to 10.1% (2004-2007) (p < 0.01). The most
      predominant variants were CRF02_AG (41.8%) and G (17.5%). Thymidine analogue
      mutations (TAMs) were more prevalent in B than non-B subtypes, in both drug-naive
      (6.2% vs. 1%; p < 0.01) and treatment-experienced patients (49% vs. 30%, p <
      0.01). K103N was most frequent in B than non-B subtypes (34% vs. 21%; p < 0.01);
      conversely, 106A/M was more prevalent in non-B than B clades (11% vs. 5%). Codon
      179 mutations associated with etravirine resistance were more frequent in non-B
      than B subtypes. Finally, secondary protease resistance mutations were more
      common in non-B than B clades, with a potentially significant impact at least on
      tipranavir. The prevalence of HIV-1 non-B subtypes has increased since the year
      2000 in a large drug resistance database in Spain, determining changes in drug
      resistance patterns that may influence the susceptibility to new antiretroviral
      drugs and have an impact on genotypic drug resistance interpretation algorithms.

PMID- 19842793
TI  - HIV type 1 fails to trigger innate immune factor synthesis in differentiated oral
      epithelium.
AB  - The oral mucosa is relatively resistant to human immunodeficiency virus type 1
      (HIV-1) transmission. The mechanisms contributing to this resistance remain
      incompletely understood, but may include HIV-induced synthesis of innate immune
      factors. We used fully differentiated oral epithelium as a surrogate for the oral
      mucosa in vivo, exposed it to X4- and R5-tropic HIV-1 in culture, and quantified
      mRNA expression of six innate immune factors. Neither virus increased expression
      of human beta defensin 2 (hBD-2) mRNA over supernatants from uninfected
      lymphoblast controls. HIV-1 also failed to induce mRNA of four additional innate
      immunity-related genes. Similar results were obtained with oral monolayer
      epithelial cells. Interestingly, the X4-tropic virus inhibited mRNA expression of
      hBD-2, and of three of the other factors, at higher dosages in the differentiated
      oral epithelium but not the monolayers. The failure of HIV-1 to induce innate
      immune factors in the differentiated epithelium was not due to a lack of tissue
      penetration, as we detected fluorescence-tagged virions up to 30 mum deep from
      the apical surface. HIV-1 does not trigger de novo innate immune factor synthesis
      in oral epithelium, pointing to the role of a constitutive innate immunity for
      protection against HIV-1 in the oral cavity.

PMID- 19842796
TI  - Stability of ciprofloxacin and norfloxacin in the presence and absence of metal
      ions in acidic solution.
AB  - A thin-layer chromatographic-densitometric method was used to determine the
      stability of ciprofloxacin and norfloxacin in the presence and absence of metal
      ions in acidic solutions at 22 degrees C, 50 degrees C and 90 degrees C. The
      degradation of ciprofloxacin and norfloxacin followed first order reaction
      kinetics in presence of metal ions. The extent of this degradation however
      depended on the type of metal ion and temperature. Product structures of
      ciprofloxacin (1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one) and
      norfloxacin (1-ethyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one) were
      determined by analysis of UV spectra and using LC-MS method.

PMID- 19842795
TI  - Ultrasound-mediated delivery of echogenic immunoliposomes to porcine vascular
      smooth muscle cells in vivo.
AB  - Vascular smooth muscle cells (VSMCs) are important targets in the treatment of
      atherosclerosis. However, the arterial media, where the majority of VSMCs reside,
      have proven to be a difficult target for drug/gene delivery. We have demonstrated
      that ultrasound enhances drug/gene delivery to VSMCs in vitro by using echogenic
      immunoliposomes (ELIPs) as the vector. This study aimed to evaluate whether
      ultrasound can similarly enhance the delivery of an agent to VSMCs, particularly
      within the arterial media, in vivo, using ELIP. Anti-smooth-muscle cell actin
      conjugated calcein-loaded ELIP were injected into the peripheral arteries of
      Yucatan miniswine (n = 8 arterial pairs). The right-sided porcine arteries were
      treated with 1-MHz continuous-wave ultrasound at a peak-to-peak pressure
      amplitude of 0.23 +/- 0.05 MPa for 2 minutes. The contralateral arteries served
      as controls. Arteries were harvested after 30 minutes and imaged with
      fluorescence microscopy. Image data were converted to grayscale and analyzed by
      using computer-assisted videodensitometry. There was significant improvement in
      calcein uptake in all three arterial layers in the arteries exposed to ultrasound
      (> 300%). This enhanced uptake was site specific and appeared limited to the
      ultrasound-treated arterial segment. We have demonstrated enhanced delivery of a
      small molecule to VSMCs in all arterial wall layers, particularly the arterial
      media, using ultrasound and targeted ELIP. The combined effect of ultrasound
      exposure and ELIP as a contrast agent and a drug/gene-bearing vector has the
      potential for site-specific therapy directed at VSMC function.

PMID- 19842797
TI  - Concomitant and feasible treatment with dasatinib and the anti-EGFR antibody
      cetuximab plus radiotherapy in a CML patient with multiple squamous neoplasias.

PMID- 19842798
TI  - Spontaneous increases in impedance following cochlear implantation: suspected
      causes and management.
AB  - Modern cochlear implant systems deliver impulse transmission rates up to 50,000
      pps. It emerged that the fast stimulation rates led to enhanced speech
      comprehension. Impedance measurement is an important aspect in cochlear implant
      testing procedures. Impedance values are a measure of the electrical resistance
      between the individual implant electrodes. Increased impedances were attributed
      frequently to inflammatory/tissue-related processes. In recent years, however, we
      have repeatedly found cases of impedance increase for which the inflammatory
      model did not provide a satisfactory explanation. The aim of this study is to
      evaluate increases in impedance in our cochlear implant population, to attempt to
      find their cause, and to formulate therapeutic hypotheses. In our cochlear
      implant programme (> 3000 recipients) we screened our database for impedance
      increases over time during device fitting. We found 16 patients with 18 affected
      ears in whom impedance increases were clearly demonstrated. We found that
      especially in cases without any sign of prior inflammation, increasing the pulse
      width of the stimulation strategy seems to be an effective tool to return
      increased impedances to normal levels.

PMID- 19842799
TI  - Wideband energy reflectance patterns in preoperative and post-operative
      otosclerotic ears.
AB  - The purpose of this study was to examine patterns of energy of reflectance (ER)
      in preoperative and post-operative conditions in otosclerotic ears. It was also
      within the scope of this paper to investigate whether the changes in ER pattern
      post-operatively correlate to the improvement in hearing as measured by pure-tone
      audiometry. ER was measured in 15 surgically confirmed otosclerotic ears (mean
      age: 44 years) before and after the stapes surgery. The most prominent change in
      ER pattern following the surgery in majority of the subjects was a sharp and deep
      drop in ER value between 700-1000 Hz. There was also a secondary wider and
      smaller increase in ER value following the surgery between 2000-4000 Hz.
      Moreover, in most cases the drop in ER values following the surgery at low
      frequencies (<or=1000 Hz) approximated the mean ER values in the normal group.
      Comparison of ER patterns with hearing improvement as measured by air conduction
      averaged across low (250-1000 Hz) and high (2000-6000 Hz) frequency bands before
      and after the surgery did not reveal any significant correlation. However, there
      was a general positive correlation trend for ER changes in low frequency band and
      AC changes, especially for high frequency bands. Changes in ER pattern may
      potentially be useful as an objective tool for monitoring the impact of the
      stapes reconstructive surgery and evaluating different surgical protocol.

PMID- 19842800
TI  - Relationships between speech perception abilities and spoken language skills in
      young children with hearing loss.
AB  - The goal of this study was to examine the relationships between scores obtained
      from measures of speech perception and language in a group of young children with
      hearing loss (HL). Eighteen children (mean age = 4.3 years) and their mothers
      participated in this study. Speech perception was measured using the online
      imitative test of speech pattern contrast perception (OLIMSPAC). Standardized
      language age equivalent scores were obtained using the Reynell developmental
      language scales-III. Number of word tokens, word types, and mean length of
      utterance (MLU) were extracted from the children's spontaneous language samples.
      Significant positive relationships were observed between children's OLIMSPAC
      scores and both standardized language scores (r ranging from 0.60 to 0.69; p
      <0.01) and all measures derived from children's spontaneous language samples (r
      ranging from 0.80 to 0.86; p<0.01). After controlling for child age, OLIMSPAC
      scores explained 34.1% of the variance in children's MLU. Using a new speech
      perception measure with reduced language demands, strong positive correlations
      were evident between speech perception and language skills for a young group of
      children with HL.

PMID- 19842801
TI  - Normal-hearing English-as-a-second-language listeners' recognition of English
      words in competing signals.
AB  - English-as-a-second-language (ESL) listeners have difficulty perceiving English
      speech presented in background noise. The current study furthered this line of
      investigations by including participants who varied widely in their age of
      English acquisition and length of English learning: 24 native English monolingual
      (EML), 12 simultaneous bilingual (SBL), 10 early ESL (E-ESL), and 14 late ESL (L
      ESL) listeners. Word recognition scores were obtained in quiet and in the
      presence of speech-weighted noise, multi-talker babble, forward-playing music,
      and time-reversed music. All words and competing signals were presented at 45 dB
      HL. EML and SBL listeners' performances were found to be similar across test
      conditions. ESL, especially L-ESL listeners, performed significantly more poorly
      in all conditions than EML and SBL listeners. Overall, speech-weighted noise and
      multi-talker babble showed greater masking effect than music; however, the
      difference in performance between L-ESL and EML listeners was the largest for the
      music maskers, indicating that L-ESL listeners are susceptible to weaker maskers.
      Age of acquisition and length of learning were both shown to be good indicators
      of SBL and ESL listeners' performance.

PMID- 19842802
TI  - Equivalent threshold sound pressure levels (ETSPL) for Sennheiser HDA 280 supra
      aural audiometric earphones in the frequency range 125 Hz to 8000 Hz.
AB  - Hearing threshold sound pressure levels were measured for the Sennheiser HDA 280
      audiometric earphone. Hearing thresholds were measured for 25 normal-hearing test
      subjects at the 11 audiometric test frequencies from 125 Hz to 8000 Hz.
      Sennheiser HDA 280 is a supra-aural earphone that may be seen as a substitute for
      the classical Telephonics TDH 39. The results are given as the equivalent
      threshold sound pressure level (ETSPL) measured in an acoustic coupler specified
      in IEC 60318-3. The results are in good agreement with an independent
      investigation from PTB, Braunschweig, Germany. From acoustic laboratory
      measurements ETSPL values are calculated for the ear simulator specified in IEC
      60318-1. Fitting of earphone and coupler is discussed. The data may be used for a
      future update of the RETSPL standard for supra-aural audiometric earphones, ISO
      389-1.

PMID- 19842803
TI  - The relationship between tinnitus pitch and the audiogram.
AB  - We studied the relationship between tinnitus pitch and the audiogram in 195
      patients. Patients with tone-like tinnitus reported a higher pitch (mean = 5385
      Hz) compared to those with a noise-like quality (mean = 3266 Hz). Those with a
      flat audiogram were more likely to report: a noise-like tinnitus, a unilateral
      tinnitus, and have a pitch < 2000 Hz. The average duration of bilateral tinnitus
      (12 years) was longer than that of unilateral tinnitus (5 years). Older subjects
      reported a less severe tinnitus handicap questionnaire score. Patients with a
      notched audiogram often reported a pitch <or=8000 Hz. Subjects with normal
      hearing up to 8000 Hz tended to have a pitch >or=8000 Hz. We failed to find a
      relationship between the pitch and the edge of a high frequency hearing loss.
      Some individuals did exhibit a pitch at the low frequency edge of a hearing loss,
      but we could find no similar characteristics among these subjects. It is possible
      that a relationship between pitch and audiogram is present only in certain
      subgroups.

PMID- 19842804
TI  - The role of anxiety sensitivity and behavioral avoidance in tinnitus disability.
AB  - The purpose of this study was to investigate the role of anxiety sensitivity and
      behavioral avoidance in tinnitus distress and functioning. A cross-sectional
      sample of 283 individuals experiencing tinnitus was obtained from an
      epidemiological national survey study on hearing loss, dizziness, and tinnitus.
      The subjects completed a series of questionnaires measuring anxiety sensitivity,
      anxiety, and depression. They also answered questions regarding tinnitus
      distress, functioning, and avoidance. Results revealed a positive significant
      correlation between anxiety sensitivity and tinnitus distress. This relationship
      was not better explained by anxiety and depression symptoms. In addition, the
      findings provided support for a model where behavioral avoidance fully mediated
      the relationship between anxiety sensitivity and tinnitus functioning, and
      partially mediated the relationship between anxiety sensitivity and tinnitus
      distress. Implications for the role of anxiety sensitivity and behavioral
      avoidance in tinnitus research are discussed.

PMID- 19842805
TI  - Development of Mandarin monosyllabic speech test materials in China.
AB  - In this study, monosyllabic Mandarin speech test materials (MSTMs) were developed
      for use in word recognition tests for speech audiometry in Chinese audiology
      clinics. Mandarin monosyllabic materials with high familiarity were designed with
      regard to phonological balance and recorded digitally with a male voice. Inter
      list equivalence of difficulty was evaluated for a group of 60 subjects (aged 18
      25 years) with normal hearing. Seven lists with 50 words each were found to be
      equivalent. These seven equivalent lists were used to measure performance
      intensity (PI) functions for a group of 32 subjects with normal hearing and a
      group of 40 subjects with mild to moderate sensorineural hearing loss. The mean
      slope of PI function was found to be 4.1%/dB and 2.7%/dB, respectively. The seven
      lists of Mandarin monosyllabic materials were found to have sufficient
      reliability and validity to be used in clinical situations.

PMID- 19842806
TI  - Music venues and hearing loss: Opportunities for and barriers to improving
      environmental conditions.
AB  - This study explores the opportunities for and barriers to improving environmental
      conditions in order to reduce the risk for music-induced hearing loss in people
      who attend music venues. Individual semi-structured interviews were held with 20
      representatives of music venues and of governmental organizations, according to a
      semi-structured interview guide. The interviews were audiotaped, transcribed, and
      systematically coded using a content-analysis technique. Reported opportunities
      to reduce music volume included improving the acoustics and installing advanced
      speaker systems. The most important barrier reported was the lack of clear
      definitions of what levels of high-volume music are hazardous. Other barriers
      mentioned included economic considerations, and the beliefs that visitors demand
      high-volume music in music venues and are personally responsible for their own
      hearing. Before measures to improve environmental conditions are implemented, the
      exact dangers of exposure to high-volume music have to be established. Evidence
      based guidelines and safety standards for leisure-time noise exposure should
      therefore be developed.

PMID- 19842807
TI  - Hearing, use of hearing protection, and attitudes towards noise among young
      American adults.
AB  - The purpose of the present study was to investigate possible associations between
      college students' attitudes, risk-taking behaviour related to noisy activities,
      and hearing problems such as threshold shifts or self-experienced hearing
      symptoms. The sample included 258 students aged between 17 and 21 enrolled at the
      University of Pennsylvania, USA. A questionnaire measuring attitudes towards
      noise, use of hearing protection, and self-reported hearing symptoms was
      distributed among the students. After completing the questionnaire a hearing
      screening, including pure-tone audiometry and tympanometry, was conducted. The
      result revealed that 26% had thresholds poorer than the screening level of 20
      dBHL. Attitudes were significantly related to self-experienced hearing symptoms,
      but not to threshold shifts. Attitudes and noise sensitivity was, significantly
      related to use of hearing protection. Hearing protection use was found in
      activities such as using firearms, mowing lawns, and when using noisy tools but
      was less reported for concerts and discotheques. It can be concluded that the
      young adults in this study expose themselves to hearing risks, since the use of
      hearing protection is in general very low.

PMID- 19842808
TI  - Fast method for psychophysical tuning curve measurement in school-age children.
AB  - The 'fast' method for measuring psychophysical tuning curves (PTC) uses a masker
      that sweeps across frequency and a Bekesy threshold tracking procedure. The fast
      PTC procedure has been recommended as a technique for diagnosing cochlear dead
      regions in adults. The aim of this study was to evaluate the fast-PTC procedure
      in children. Twelve normal-hearing children (7-10 years old) and five adults were
      tested. The fast-PTCs were measured for 1000 and 4000 Hz signals using ascending
      and descending masker sweeps. Measurements were repeated on a separate day to
      assess test-retest variability. All children were able to perform the task;
      however it was possible to define the tip in only 87% of the fast-PTCs. Although
      the variability in tip frequency was higher for children, the mean difference
      between children and adults was not statistically significant. As expected, the
      difference on retest was higher for children. Studies investigating the use of
      the fast-PTC procedure with hearing-impaired children are warranted.

PMID- 19842809
TI  - Use of a revised children's implant profile (GOSHChIP) in candidacy for
      paediatric cochlear implantation and in predicting outcome.
AB  - The aims of this study were to investigate statistically the way a revised
      version of the children's implant profile (GOSHChIP) is used to inform candidacy
      decisions and explore its utility in predicting outcomes in the first three years
      of implant use. A retrospective case series analysis design was employed. Data
      were collated for 127 children with a mean age of 4.7 years at implantation.
      Concerns in a number of areas of the child's pre-implant functioning as rated on
      the GOSHChIP (spoken or manual communication skills, cognitive abilities, family
      structure and support, and use of hearing aids) were associated with speech
      perception and intelligibility outcomes following implantation. In terms of non
      verbal cognitive abilities, the score on tests of fluid reasoning skills
      (sequencing), that contributes to the cognitive factor on the GOSHChIP, was found
      to significantly predict speech perception and speech intelligibility post
      implant. The GOSHChIP is a useful tool in making paediatric cochlear implant
      candidacy decisions, and in forming a guide for counselling parents about the
      potential benefit their child may receive from an implant.

PMID- 19842810
TI  - Electrical stimulation rate effects on speech perception in cochlear implants.
AB  - The objective of this study was to explore cochlear implant users' speech
      perception performance in quiet and in noise for low to moderate stimulation
      rates. Eight postlingually deaf adult users of the Nucleus CI24 cochlear implant
      (contour electrode array) using the ESPrit 3G speech processor participated in
      this study. Monosyllabic word recognition in quiet and sentence perception in
      noise was evaluated for low to moderate stimulation rates of 275, 350, 500, and
      900 pulses-per-second/channel (pps/ch). All four stimulation rate programs were
      balanced for loudness. A repeated ABCD experimental design was employed. Take
      home practice was provided with each stimulation rate. Subjects also responded to
      a comparative questionnaire to examine their rate preference for a variety of
      listening situations. Results for six of the eight subjects showed no significant
      effect of rate for monosyllables in quiet. However, results for the sentence test
      in noise demonstrated improvements with 500 or 900 pps/ch stimulation rates in
      seven out of the eight subjects. Although there was not a close relationship
      between each subject's subjective preference and the rate program that provided
      best speech perception, most subjects indicated a preference for 500 pps/ch rate
      in noise.

PMID- 19842811
TI  - Psychometric properties of a Chinese (Cantonese) version of the Tinnitus
      Questionnaire.
AB  - The objective of this study was to determine the psychometric properties of a
      Chinese (Cantonese) version of the Tinnitus Questionnaire (TQ), which is a
      psychometric self-report measure of perceived tinnitus-related distress. The
      subjects were 114 adults who attended audiology clinics with a primary or
      secondary complaint of tinnitus. They completed the Chinese versions of the TQ
      (TQ-CH), Short-Form 36 Health Survey (SF-36), and Hospital Anxiety and Depression
      Scale (HADS). The subjective severity of tinnitus and tinnitus-related problems
      were scored using rating scales. The TQ-CH and its subscales had good internal
      consistency reliability estimates (alpha=0.75-0.94), which were comparable to
      those of the original version. Significant correlations were observed between the
      TQ-CH and psychological distress, tinnitus-related problem ratings, and severity
      ratings. Factor analysis showed the high construct validity of the TQ-CH
      subscales. High test-retest reliablity (intraclass correlation coefficient=0.96)
      was observed. The results suggest that the TQ-CH is a reliable and valid measure
      of general tinnitus-related distress that can be used in clinical settings to
      quantify the impact of tinnitus on daily living.

PMID- 19842812
TI  - Development of distortion product otoacoustic emissions in C57BL/6J mice.
AB  - Distortion product otoacoustic emissions (DPOAEs) have been used to examine the
      development of hearing in the rat and gerbil. However, no reports of DPOAE
      measurement from the onset of hearing in mice are available. Commercially
      available components were assembled and adapted to provide a suitable probe
      microphone and sound delivery system for measuring DPOAE in developing C57BL/6J
      mice. Furthermore, DPOAE data were compared with the findings of the auditory
      brainstem response (ABR). DPOAEs were obtained at 8 kHz from 11 days after birth,
      20 kHz from 12 days, and 30 kHz from 13 days. Adult-like patterns of DPOAE were
      obtained 21 days at 8 and 20 kHz, and 28 days at 30 kHz. On the other hand, the
      ABR thresholds at 12 to 36 kHz appeared between 11 and 12 days and were saturated
      at 14 days. Based on these data, the onset of measureable DPOAEs in the mouse
      were earlier than in the rat and gerbil. The maturation of DPOAE in the mouse
      begins at a lower frequency in the high frequency range. In addition, the ABR
      threshold reached maturation earlier than DPOAE.

PMID- 19842813
TI  - Cortical auditory steady-state responses to low modulation rates.
AB  - This paper describes low-frequency auditory steady-state responses (ASSRs) to
      speech-weighted noise stimuli. The effect of modulation frequency was evaluated
      within the frequency range below 40 Hz. Furthermore, objective ASSR measures were
      related to speech understanding performance in normal-hearing and hearing
      impaired listeners. The variability in ASSR recordings over independent test
      sessions was larger between subjects than within. Trends of increased responses
      around 10 and/or 20 Hz were found in all subjects. Obtained latency estimates of
      the responses pointed to primarily cortical sources involved in ASSR generation
      at low frequencies. Furthermore, significant differences between normal-hearing
      and hearing-impaired adults were found for ASSRs to stimuli related to the
      temporal envelope of speech. Comparing these responses with phoneme
      identification scores over different stimulus levels showed both measures
      increased with stimulus level in a similar way (rho=0.82). At a fixed stimulus
      level, ASSRs were significantly correlated with speech reception thresholds for
      phonemes and sentences in noise (rho from -0.45 to -0.53). These results indicate
      that objective low-frequency ASSRs are related to behavioral speech
      understanding, independently of level.

PMID- 19842814
TI  - Short-term hearing fluctuation in Meniere's disease.
AB  - This study aimed to assess the extent and implications of short-term hearing
      fluctuation in Meniere's disease. Thirty-six subjects diagnosed with Meniere's
      were recruited to measure their own hearing using in-situ audiometry via a
      hearing aid (Widex Diva) and a portable programmer (SP3). Self-hearing tests
      measuring up to 14 frequency bands were conducted three times a day over eight
      weeks using the expanded Sensogram. Twenty-three ears showed low frequency
      fluctuation while ten fluctuated in mid frequencies with some 'double peak'
      audiogram configurations. Eight ears in the later stages of Meniere's, contrary
      to expected, also recorded fluctuation across all frequencies. Self-hearing
      testing Meniere's ears over eight weeks revealed great hearing fluctuation with
      significant changes in audiogram configuration. It suggests that as endolymphatic
      hydrops progresses through the cochlea, low frequency fluctuation is followed by
      fluctuation in the mid frequencies, leading to fluctuation across all
      frequencies. Use of a self-hearing test may facilitate diagnosis and hearing aid
      fitting for this population, as clinical audiograms may not provide accurate
      information of hearing fluctuation.

PMID- 19842816
TI  - Should we empower the family?

PMID- 19842817
TI  - Persons with mild and moderate Alzheimer's disease use verbal-instruction
      technology to manage daily activities: effects on performance and mood.
AB  - OBJECTIVE: To extend the evaluation of verbal-instruction technology for helping
      persons with mild and moderate Alzheimer's disease recapture daily activities and
      improve their mood. METHODS: Two studies targeted two activities (i.e. snack
      preparation/sharing and shaving) with six and three new participants,
      respectively. Intervention effects on activity performance were assessed through
      non-concurrent multiple baseline designs across participants. The impact of
      intervention (activity) on mood was assessed by recording indices of happiness or
      indices of unhappiness during activity and non-activity trials. RESULTS: The use
      of a technology providing verbal instructions helped all participants perform the
      target activities. Performance was largely accurate with seven of the
      participants. Eight of the participants also showed mood improvement (i.e.
      increases in indices of happiness or decreases in indices of happiness) during
      activity. CONCLUSION: These results suggest that the approach reported may be a
      useful strategy for helping persons with Alzheimer's disease enhance their
      activity and mood.

PMID- 19842818
TI  - Children's reports of activity and participation after sustaining a spinal cord
      injury: a cognitive interviewing study.
AB  - OBJECTIVE: To evaluate the readability, comprehension and response processes of
      test items designed to measure activity performance and participation by children
      with spinal cord injury (SCI). METHODS: Eleven parents and 33 children
      participated. Descriptive statistics were used to calculate frequency of problems
      based on age, grade, domain and response scale. Agreement was evaluated by
      weighted kappa coefficient values. RESULTS: Most (54%) of the problems were due
      to reading/comprehension, with the majority by children 8 years of age or younger
      (56%) who had not completed 2nd grade (51%). Agreement between child-parent
      reports ranged from poor-good, with strongest agreement for mobility items and
      weak agreement for chores, self-care and participation. CONCLUSION: Children with
      SCI 8 years of age and older who have competed 2nd grade are able to read,
      understand and respond to items associated with activity performance and
      participation.

PMID- 19842819
TI  - Observed behaviours of pre-term children in a social play situation with
      classroom peers.
AB  - BACKGROUND: A number of studies have reported social adjustment problems in pre
      term children. OBJECTIVES: To observe the pre-term's behaviour in an experimental
      situation and correlate these observed behaviours with the children's peer-rated
      social behaviours (withdrawal, aggression and sociability/leadership). METHODS:
      Of 56 pre-term children, 24 were classified as the sick pre-term (SPT) group and
      32 children as the healthy pre-term (HPT) group. The comparison group comprised
      56 healthy full-terms. The experimental situation used a game called Rush Hour, a
      labyrinth-type board game. The play situation was videotaped and behaviours
      (number of consecutive moves) were coded in real time. RESULTS: At 12 years of
      age, the sick pre-term (SPT) group exhibited fewer consecutive moves during the
      game than the other two groups, especially when the task became more complex
      (involving four consecutives moves). Moreover, the Complex Task Index was
      correlated with the social withdrawal score rated by peers. CONCLUSION: The at
      birth sick pre-term gradually became less involved in a complex decision-making
      task and this was understood as a lesser ability to make a decision in a complex
      setting.

PMID- 19842820
TI  - Memory strategy development in children with foetal alcohol spectrum disorders.
AB  - OBJECTIVE: The goal of this study was to examine whether children with foetal
      alcohol spectrum disorders (FASD) show the same developmental transition from
      visual to verbal memory strategies as in non-FASD children and whether this
      transition was related to executive functioning and vocabulary skills. METHODS:
      Younger (5-6 years) and older (8-10 years) children with FASD and non-FASD
      children were tested on a picture memory task. RESULTS: Among both age groups,
      the non-FASD children performed better than those with FASD. Younger children
      with FASD appeared to use a visual approach, whereas older children with FASD
      appeared to use a verbal approach. However, among the non-FASD group both age
      groups appeared to use a verbal approach. Among the FASD group, the transition
      from a visual to verbal approach was correlated with executive functioning
      skills. IMPLICATIONS: Strategies for classroom approaches as well as strategy
      training are discussed.

PMID- 19842821
TI  - Evaluation of an adaptive ice skating programme for children with disabilities.
AB  - OBJECTIVE: To describe an adaptive ice skating programme designed by paediatric
      therapists. METHODS: Twenty-two children, ages 5-12 years, with developmental
      disabilities participated in this once per week skating programme lasting 6
      weeks. Ice skating instructors led the group lessons, while university student
      coaches provided individualized assistance to the children. The programme was
      evaluated using a summative evaluation design. Outcomes included participant
      attendance, incidence of injuries, skating skills and parent and student coach
      survey data. RESULTS: On average, participants attended 83% of the sessions and
      one minor injury was reported. Participants' parents were very satisfied with the
      programme and reported improvements in their child's skating skills, leg
      strength, endurance, balance, self-esteem/confidence and ability to participate
      in a group. Student coaches also reported high levels of satisfaction with this
      programme and reported similar improvements in the children they coached.
      CONCLUSION: The programme appeared promising, but may require minor
      modifications.

PMID- 19842822
TI  - Virtual reality in paediatric rehabilitation: a review.
AB  - OBJECTIVE: To provide a narrative review of studies regarding the outcomes of
      Virtual Reality (VR)-based treatment and rehabilitation programmes within the
      paediatric population. METHODS: Studies related to the use of VR across a number
      of paediatric areas (e.g. cerebral palsy, autism, foetal alcohol syndrome and
      attention deficits) were identified and summarized. RESULTS: Outcomes from the
      studies reviewed provide preliminary support for the use of VR. CONCLUSION: VR
      may be an effective treatment method for specific disorders, although the
      generalizability of this literature is hindered by several methodological
      limitations, such as small samples and the absence of appropriate control
      participants.

PMID- 19842823
TI  - A review of the verbal and visual memory impairments in children with foetal
      alcohol spectrum disorders.
AB  - BACKGROUND: Children with Foetal Alcohol Spectrum Disorders (FASD) have
      significant impairments in memory, negatively affecting academics and daily
      functioning. PRIMARY OBJECTIVE: To review published research on: (1) verbal and
      visual-spatial memory in children with FASD or prenatal alcohol exposure (PAE);
      (2) animal research on the impact of PAE on memory; and (3) brain areas involved
      in memory that are affected by PAE. MAIN OUTCOMES: Verbal memory is one of the
      main areas of memory affected by gestational alcohol exposure, specifically in
      encoding and retrieving information. Spatial memory has emerged as a dominant
      deficit in individuals with FASD, consistent in children, adolescents and adults.
      There are regions of the brain more typically affected by PAE, which have ties to
      memory functioning. Animal research has confirmed the presence of impacts to key
      brain regions involved in memory functioning for those affected by PAE.
      CONCLUSION: Memory deficits are a prevalent finding in individuals with PAE.
      Research in this area is complicated by small sample sizes, difficulty linking
      animal research to human application and lack of effective connection between
      existing memory theory and functional memory testing in FASD. New research has
      shown that there are implications for memory and learning amelioration in
      children with FASD.

PMID- 19842824
TI  - Some literary accounts of possible childhood paraplegia and neurorehabilitation.
AB  - OBJECTIVE: To identify examples of the practice of neurorehabilitation in 19th
      and early 20th century NOVELS. METHODS: Four case of apparent childhood
      paraplegia, which date from the late 19th and early 20th centuries, are
      described. The approaches to facilitate clinical recovery are summarized.
      RESULTS: Common themes identified in these four literary accounts include a
      passive approach to intervention, use of specialist input and provision of other
      treatments (e.g. baths, iron braces). CONCLUSION: These literary accounts may,
      despite all their acknowledged shortcomings, give some insights into contemporary
      lay concepts of neurorehabilitation.

PMID- 19842825
TI  - Brief motivational interventions for HIV/STI risk reduction among individuals
      receiving alcohol detoxification.
AB  - This HIV/STI risk reduction clinical trial implemented in short-term alcohol
      detoxification employed a randomized block design to evaluate three intervention
      conditions for feasibility, safety, and potential for changing sexual risk
      attitudes, motivations, and behavior: (a) nonintervention control (standard HIV
      information dissemination), (b) brief motivational intervention (BMI) for
      resolution of ambivalence and sex risk reduction planning, and (c) BMI with
      biological feedback based on testing for sexually transmitted infections (STIs).
      Findings revealed that BMI can be feasibly implemented during detoxification
      treatment with individuals with significant substance impairment. BMI, whether
      coupled with biological feedback or not, enhanced motivation for increasing
      behaviors that protect from STI. Sexual risk behavior did not change in any of
      the groups to a statistically significant degree; however, additional analyses
      suggest negative biological feedback may have resulted in slightly increased
      level of sexual activity, undoing behavioral effects of increased motivation for
      sexual risk reduction, perhaps by distorting participants' perception of risk.

PMID- 19842826
TI  - Sociocultural contexts and communication about sex in China: informing HIV/STD
      prevention programs.
AB  - HIV may be particularly stigmatizing in Asia because of its association with
      "taboo" topics, including sex, drugs, homosexuality, and death (Aoki, Ngin, Mo, &
      Ja, 1989). These cultural schemata expose salient boundaries and moral
      implications for sexual communication (Chin, 1999, Social Science and Medicine,
      49, 241-251). Yet HIV/STD prevention efforts are frequently conducted in the
      public realm. Education strategies often involve conversations with health
      "experts" about condom use, safe sex, and partner communication. The gap between
      the public context of intervention efforts and the private and norm-bound nature
      of sex conversation is particularly challenging. Interviews with 32 market
      workers in eastern China focused on knowledge, beliefs, and values surrounding
      sexual practices, meanings, and communication. Sex-talk taboos, information
      seeking, vulnerability, partner communication, and cultural change emerged as
      central to understanding intervention information flow and each theme's relative
      influence is described. Findings illustrate the nature of how sexual
      communication schemata in Chinese contexts impact the effectiveness of sexual
      health message communication.

PMID- 19842827
TI  - STIs and HIV among men having sex with men in China: a ticking time bomb?
AB  - Over the past 10 years, HIV infection rate has increased annually from 30% to 40%
      in China, resulting in over 700,000 Chinese living with HIV/AIDS by the end of
      2007. The Chinese National Medium and Long-Term Strategic Plan for HIV/AIDS
      Control and Prevention (1998-2010) identifies the men who have sex with men (MSM)
      population as a high-risk group for HIV infection. The latest statistics show
      that MSM account for 11.1% of all HIV/AIDS cases in China, an alarming rising
      rate in a country with one fourth of the world's population. To help expanding
      the emerging foundation of scientific and empirical data on Chinese MSM, several
      multidivisional research initiatives have been initiated. For example, the China
      National Center for AIDS/STD Prevention and Control recently launched a national
      study targeting above 26,000 MSM in 61 cities in 2008. Other programs, targeted
      prevention measures for the estimated 5-10 million-Chinese MSM, including
      stronger promotion of condom use, expanded coverage and quality of HIV prevention
      activities, increased access to voluntary HIV counseling-and-testing services,
      and improved access to treatment for sexually transmitted infections. To
      complement these initiatives, this article aims to provide a comprehensive review
      and analysis of the (a) scientific and empirical literature (both in English and
      Chinese) on HIV/sexually tranmitted infection (STI) prevention targeting Chinese
      MSM, and (b) existing programmatic and policy efforts targeting Chinese MSM at
      risk for STIs (including HIV). Finally, four recommendations for future endeavors
      targeting this high-risk group are drawn from the above analyses.

PMID- 19842828
TI  - Communication and the antiretroviral treatment rollout: beyond the medical model.
AB  - With the advent of antiretroviral treatment (ART) for HIV/AIDS, governments and
      NGOs seek to increase the number of persons on this lifesaving medication and
      their adherence to the drug regimens. The conventional approach to communication
      within a clinical context includes provider-patient counseling, group education
      sessions, client information materials, and support groups. Given the layers of
      influence on an individual's behavior-spouse/family/friends, community, and
      societal-it is essential for the ART rollout to harness the power of
      complementary communication channels to create an enabling environment that
      supports individual behavior in terms of adherence. This article explores a
      series of communication vehicles-different forms of mass media and community
      mobilization-that complement the interpersonal communication/counseling within
      the medical model, and it provides examples from developing countries (largely
      sub-Saharan Africa) that have used them to good effect in the rollout of ART.

PMID- 19842829
TI  - Predictors of condom use among men enrolled in drug treatment programs.
AB  - This study identified predictors of condom use and developed a model of condom
      use in a sample of men (n = 324) enrolled in drug treatment. Utilizing a series
      of logistic regression analyses reported condom use was predicted by possession
      of condoms, future intention to use condoms, future intention to increase condom
      use, having a high-risk partner, low Condom Barriers Scale scores, being
      unmarried and ethnic minority status. A probit path analysis revealed the
      following model of condom use among men in drug treatment: Taking condoms from
      clinic stocks was the best predictor of condom possession, which in turn was the
      best predictor of condom use. These study findings identify condom availability
      in treatment programs as an important risk reduction intervention. Treatment
      programs can apply these predictors of condom use to better identify individuals
      at risk for HIV and sexually transmitted infections to better target prevention
      interventions.

PMID- 19842830
TI  - HIV seroprevalence in a sample of Tanzanian intravenous drug users.
AB  - Injection drug use has recently emerged in sub-Saharan Africa. The purpose of
      this study was to assess the factors associated with increased risk of testing
      HIV-positive in a sample of injection drug users (IDUs) in Dar es Salaam,
      Tanzania. Participants were recruited by a trained outreach worker or were
      referred by IDUs who had completed the study. Blood specimens and self-reported
      socioeconomic and behavioral data were collected from 315 male and 219 female
      IDUs. Data were analyzed using univariate odds ratios and multivariate logistic
      regression modeling. Forty-two percent of the sample tested HIV-positive. Several
      socioeconomic, injection, and sexual factors were found to be associated with
      increased odds of testing HIV-positive. Multivariate analysis showed that having
      had sex more than 81 times in past 30 days, earning less than 100,000 shillings
      (US$76) in the past month, residency in Dar es Salaam for less than 5 years, and
      injecting for 3 years were independently associated with the greatest risk of
      infection. The rate of HIV infection in this sample of IDUs was found to be very
      high, suggesting that injection drug use may be a factor in the continuing
      epidemic in sub-Saharan Africa. The factors associated with increased risk of HIV
      infection suggest further research is needed on the needle use and sexual
      networks of IDUs.

PMID- 19842832
TI  - Signal transduction pathways linking the activation of alveolar macrophages with
      the recruitment of neutrophils to lungs in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a major and increasing global
      health problem. It is predicted by the World Health Organization to become the
      third most common cause of death and the fifth most common cause of disability in
      the world by 2020. COPD is a complex inflammatory disease involving several types
      of inflammatory cells and multiple inflammatory mediators. Although abnormal
      numbers of inflammatory cells such as macrophages, dendritic cells, neutrophils,
      and T lymphocytes have been documented in COPD, the relationship between these
      cell types and the sequence of their appearance and persistence is largely
      unknown. Alveolar macrophages have been identified as one of the major cell types
      that plays a key role in orchestrating the inflammatory events associated with
      the pathophysiology of COPD. One of the major functions of macrophages is the
      secretion of chemotactic factors and this function is markedly increased on
      exposure to cigarette smoke (CS). This enhanced release of chemoattractants
      results in increased lung neutrophil infiltration, which is thought to be a key
      event in the development of COPD. The molecular basis for this amplified
      inflammatory response is not very clear, but it could be due to an alteration in
      signal transduction pathways within the macrophage. Based on existing literature,
      an attempt has been made to create a comprehensive review of the signal
      transduction pathways that link the activation of macrophages with the increased
      recruitment of neutrophils into the airways. Some of the major stimuli that
      activate macrophages and cause them to secrete chemotactic factors have been
      identified as CS, wood smoke, ozone, bacterial endotoxin, and proinflammatory
      cytokines such as interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha.
      These stimuli seem to activate mainly redox-sensitive transcription factors such
      as nuclear factor (NF)-kappa B and activator protein (AP)-1, both of which play a
      major role in the synthesis and secretion of chemotactic factors such as IL-8 and
      leukotriene B(4) (LTB(4)). The pathways involved in the synthesis and secretion
      of other factors such as macrophage chemotactic protein-1 (MCP-1) and growth
      related oncogene-alpha (Gro-alpha) have also been reviewed.

PMID- 19842831
TI  - Risk perception and beliefs regarding HIV infection among Ethiopian immigrants.
AB  - In Ethiopia, approximately 7.5% of the urban population is HIV-positive, and
      countrywide 1.5 million people are living with HIV. Between 1990 and 2000,
      immigration into the United States by African-born immigrants increased by 130%.
      Of this immigrant population, individuals from Ethiopia make up a significant
      portion. Although there is a rich literature addressing the beliefs regarding HIV
      and risk perception among some immigrant populations in the United States, few
      studies target Ethiopian-born residents. Thus, a survey-based study addressing
      demographics, acculturation, awareness, beliefs and risk perception, attitudes
      toward susceptibility for infection, and risk behaviors targeted Ethiopian-born
      residents of San Diego, California. Results indicate a separation between
      understanding of HIV transmission and personal risk perception for infection in a
      young, highly educated, predominantly male participant pool. As an initial study
      of HIV beliefs and risk perception in the immigrant Ethiopian population, our
      results provide information on specific areas warranting further investigation.

PMID- 19842833
TI  - A proliferation-inducing ligand: a new biomarker for non-small cell lung cancer.
AB  - To identify a proliferation-inducing ligand (APRIL) expression profile in tumor
      tissue and sputum of lung cancer, and evaluate the possibility of an assistant
      diagnosis of lung cancer by real-time fluorescence quantitative polymerase chain
      reaction (RTQ-PCR) in sputum as well, the authors analyzed the expression of
      APRIL mRNA in 75 tissue samples and 71 corresponding sputum samples of lung
      cancer by RTQ-PCR and analyzed their correlation. APRIL protein expression was
      also observed in tumor tissues by Western blot and immunohistochemistry. The
      expression analysis revealed APRIL expression was elevated in non-small cell lung
      cancer (NSCLC) and the expression of APRIL protein was located in the membrane
      and cytoplasm of tumor cells by immunohistochemiscal staining. Compared to benign
      pulmonary disease and healthy volunteers, the expression of APRIL mRNA in sputum
      of lung cancer was elevated (both P <. 001). When cut-off values for positivity
      were set at the mean + 2SD of mRNA expression in healthy volunteers, the positive
      rate for APRIL mRNA expression was 81.7% (58/71) in sputum samples of lung
      cancer, 3.2% (2/62) in benign pulmonary disease, and 1.5% (1/65) in healthy
      volunteers. The correlation was evident between the expression level of APRIL
      mRNA of tissue samples and that of sputum samples (P <. 001, r =. 702). These
      results support the possibility that the APRIL gene may play a key role in lung
      cancer, especially in NSCLC. The elevated expression level of APRIL mRNA in
      sputum of NSCLC suggested that APRIL mRNA may serve as an effective and
      convenient diagnostic biomarker for NSCLC.

PMID- 19842834
TI  - Cell-based therapy improves cell viability and increases airway size in an
      explant model.
AB  - Cell-based therapy is a promising treatment option for lung disease, but no
      studies have demonstrated its benefit in promoting perinatal lung growth.
      Embryonic day 18 (E18) fetal lungs treated with vascular inhibitors were grown as
      explant organ cultures to inhibit endothelial growth in the explant cultures.
      Disruption of pulmonary vasculature decreased explant mean cord length and
      viability, whereas coculture with fetal pulmonary or predifferentiated embryonic
      stem cells rescued both parameters. These results demonstrate in a model of
      perinatal lung growth, exogenous addition of fetal pulmonary cells or
      differentiated embryonic stem (ES) cells promotes survival and alveolar
      morphogenesis. These experiments represent the first evidence of the benefits of
      cell-based therapy for perinatal lung growth.

PMID- 19842835
TI  - Chemokine receptors in a regulation of interstitial lung fibrosis and
      inflammation.
AB  - Sarcoidosis and extrinsic allergic alveolitis (EAA) are granulomatous lung
      diseases with predominantly Th1 immune response. In this prospective study, the
      authors analyzed the expression of chemokine receptors CXCR2, CXCR3, and CCR3 on
      bronchoalveolar lavage fluid (BALF) CD4 T cells of patients either with EAA or
      sarcoidosis. The authors investigated the correlation of chemokine receptors
      expression, lymphocyte and neutrophil counts in BALF, and high-resolution
      tomography (HRCT) pattern. Thirteen sarcoidosis and 6 EAA patients were enrolled
      in the study. The expression of chemokine receptors on BALF CD4 T cells were
      analyzed by flow cytometry. HRCT scoring system according to Kazerooni was used
      for evaluation of the disease extent. The authors have found positive correlation
      between BALF CD4 T-cell CXCR3 expression and HRCT alveolar score in EAA patients
      (P <. 01). CXCR2 expression on BALF CD4 T cells and interstitial HRCT score did
      not show a correlation either in the EAA or the sarcoidosis group. Positive
      correlation between CCR3 expression on CD4+ T cells and HRCT interstitial score
      was proven in the EAA group (P <. 05). The authors conclude that Th2 predominant
      immune response may play an important role in chronic EAA pathogenesis. The role
      of chemokine receptors in the pathogenesis of EAA and sarcoidosis should be
      presumed and investigated.

PMID- 19842836
TI  - Vitamin D status in relation to nutritional depletion and muscle function in
      patients with advanced pulmonary disease.
AB  - Muscle weakness is an important complication of advanced pulmonary disease and it
      is associated with reduced functional activity and lower survival. Vitamin D may
      be involved in muscle function. The aim of this study was to investigate
      determinants of calcidiol (25-hydroxycholecalciferol, the major circulating
      indicator of vitamin D) status and associations between vitamin D metabolites and
      muscle function in relation to nutritional depletion. Fifty-two percent of the
      underweight patients (n = 42) and 55% of the normal-weight ones (n = 29) had
      vitamin D deficiency (< 37.5 nmol/L). The resulting models of linear regression
      showed that, for the calcidiol model, 24.7% of the variation for calcidiol was
      explained by fat mass index, vitamin D intake, and FEV(1)/FVC. The results
      further suggested that vitamin D intake was a stronger predictor of calcidiol
      status in the underweight patients than in the normal-weight ones. In the
      resulting models for 6-minute walking distance, calcidiol was a significant
      predictor, which tended to be more marked in the underweight patients than in the
      normal-weight ones. Low serum calcidiol concentration was associated with fat
      mass, lung obstruction, and low intake of vitamin D, especially in the
      underweight patients, and calcidiol was a predictor of walking distance.

PMID- 19842838
TI  - Extracorporeal photopheresis in a rat model of pulmonary fibrosis.
AB  - Extracorporeal photopheresis has anti-inflammatory properties. The development of
      pulmonary fibrosis includes inflammatory episodes. This study evaluates effects
      of extracorporeal photopheresis in experimental pulmonary fibrosis. The bleomycin
      model of pulmonary fibrosis was used. Two groups of 4 rats received intratracheal
      bleomycin to induce fibrosis. The treatment group received infusions of
      photochemically treated leukocytes harvested from syngeneic animals. All animals
      were sacrificed at day 21 after fibrosis induction and analyzed with respect to
      lung histology and hydroxyproline content, cellular composition of
      bronchoalveolar lavages, serum and lavage concentrations of transforming growth
      factor-beta, interferon-gamma, and interleukin-10, and expression of selected
      genes in the lung. Interleukin-10 and transforming growth factor-beta protein
      concentrations increased in the plasma of treated animals, whereas the interferon
      gamma protein concentration was higher in bronchoalveolar lavages. Interferon
      gamma gene expression was up-regulated in the lung tissue of treated animals. No
      significant differences between treated and untreated animals were found with
      respect to hydroxyproline, histology, and lavage cell count. To conclude,
      extracorporeal photopheresis has positive molecular effects but does not
      attenuate experimental lung fibrosis with respect to histology, hydroxyproline,
      and lavage cell count in the applied treatment regimen. Further investigations of
      extracorporeal photopheresis in experimental pulmonary fibrosis are justified.

PMID- 19842839
TI  - Modulation of nitrosative/oxidative stress in the lung of hyperglycemic rabbits
      by two antidiabetics, pioglitazone and repaglinide.
AB  - The lungs are involved in diabetes in the cause of the complex phenomena diabetes
      generates. In the present study, hyperglycemia inhibited pulmonary antioxidants,
      including superoxide dismutase, catalase, glutathione peroxidase, and
      glutathione. These effects were accompanied by significant elevation of lipid
      peroxidation, total nitrites, and nitrotyrosine levels. The study investigated
      the effects of 2 oral antidiabetics, pioglitazone and repaglinide, on the
      mentioned parameters. It is concluded that pioglitazone exerts protective effect
      in the lung by inhibiting nitrosative stress and normalizing the nitrites and
      nitrotyrosine levels. Administration of repaglinide prevents oxidative and, to a
      smaller extent, nitrosative changes.

PMID- 19842840
TI  - The effects of hyperoxia exposure on lung function and pulmonary surfactant in a
      rat model of acute lung injury.
AB  - The objective of this study was to determine if prolonged hyperoxia exposure
      would deplete antioxidants, resulting in excessive oxidative stress that would
      lead to oxidation of pulmonary surfactant and contribute to lung dysfunction.
      Rats were exposed to either hyperoxic (> 95% O(2)) or normoxic (21% O(2)) oxygen
      concentrations for 48 or 60 hours. Pulmonary compliance, inflammatory cells, and
      total protein levels were measured as indicators of lung injury. Bronchoalveolar
      lavage (BAL) samples were analyzed for surfactant composition, antioxidant
      content, and markers of oxidative stress. Antioxidants were also measured in lung
      tissue and plasma samples. Hyperoxia exposure for 60 hours resulted in increased
      protein and inflammatory cells in BAL, and lower pulmonary compliance, compared
      to all other groups. Total surfactant and surfactant large aggregates were
      increased following 48 hours of hyperoxia exposure, with a further increase
      following 60 hours. Animals exposed to 60 hours of hyperoxia also demonstrated
      lower ascorbate levels in lung tissue, increased lipid peroxides in BAL, and
      increased oxidation of phosphatidylglycerol species in surfactant. This study
      demonstrates that the balance of oxidant/antioxidant components is disrupted
      within the lung during periods of hyperoxia, and that although surfactant lipids
      may be susceptible to oxidative damage, they do not likely represent a major
      mechanism for the lung dysfunction observed.

PMID- 19842841
TI  - A comparison of two sets of microarray experiments to define allergic asthma
      expression pattern.
AB  - Allergic asthma is a complex trait. Several approaches have been used to identify
      biomarkers involved in this disease. This study aimed at demonstrating the
      relevance and validity of microarrays in the definition of allergic asthma
      expression pattern. The authors compared the transcript expressions of bronchial
      biopsy of 2 different microarray experiments done 2 years apart, both including
      nonallergic healthy and allergic asthmatic subjects (n = 4 in each experiment).
      U95Av2 and U133A GeneChips detected respectively 89 and 40 differentially
      expressed genes. Fifty-five percent of the U133A genes were previously identified
      with the U95Av2 arrays. The immune signaling molecules and the proteolytic
      enzymes were the most preserved categories between the 2 experiments, because 3/4
      of the genes identified by the U133A were also significant in the U95Av2 study
      for both categories. These results demonstrate the relevance of microarray
      experiments using bronchial tissues in allergic asthma. The comparison of these
      GeneChip studies suggests that earlier microarray results are as relevant as
      actual ones to target new genes of interest, particularly in function categories
      linked to the studied disease. Moreover, it demonstrates that microarrays are a
      valuable technology to target novel allergic asthma pathways as well as
      biomarkers.

PMID- 19842843
TI  - Vitamin A supplementation induces oxidative stress and decreases the
      immunocontent of catalase and superoxide dismutase in rat lungs.
AB  - Lungs require an adequate supply of vitamin A for normal embryonic development,
      postnatal maturation, and maintenance and repair during adult life. However,
      recent intervention studies revealed that supplementation with retinoids resulted
      in a higher incidence of lung cancer, although the mechanisms underlying this
      effect are still unknown. Here, the authors studied the effect of vitamin A
      supplementation on oxidative stress parameters in lungs of Wistar rats. Vitamin A
      supplementation either at therapeutic (1000 and 2500 IU/kg) or excessive (4500
      and 9000 IU/kg) doses for 28 days induced lipid peroxidation, protein
      carbonylation, and oxidation of protein thiol groups, as well as change in
      catalase (EC 1.11.1.6; CAT) and superoxide dismutase (EC 1.15.1.1, SOD)
      activities and immunocontents. These results altogether suggest that vitamin A
      supplementation causes significant changes in redox balance the free radical
      status in lungs, which are frequently associated to severe lung dysfunction.

PMID- 19842842
TI  - Simvastatin restores down-regulated GATA-6 expression in pulmonary hypertensive
      rats.
AB  - Vascular smooth muscle cell proliferation has been known to be predominant in
      vascular remodeling of pulmonary hypertensive. The GATA family proteins, a group
      of zinc finger transcription factors, play an important role during cell
      proliferation. The aim of present study was to investigate the expression of GATA
      6 gene in experimental pulmonary hypertensive rats and explore the effect of
      regulation of GATA-6 expression by simvastatin on pulmonary vascular remodeling.
      The male Sprague-Dawley rats model was established with receiving pneumonectomy
      and monocrotaline (MCT) administration. Right pulmonary artery remodeling in
      these animals was compared with untreated rats or rats receiving simvastatin. The
      level of GATA-6 mRNA and protein expression was detected by reverse transcriptase
      polymerase chain reaction (RT-PCR) and Western blotting, respectively.
      Pneumonectomized, MCT-treated rats had significantly increased mean pulmonary
      arterial pressure (mPAP), RV/(LV + S) ratio (ratio of the right ventricular to
      left ventricular and septum weights), vascular occlusion scores (VOSs), and
      percent media wall thickness on day 35, all the indices were significantly
      decreased after simvastatin administration in these rats. The level of GATA-6
      mRNA and protein were markedly decreased in these pneumonectomy and MCT-treated
      rats, and they were significantly up-regulated in these rats after receiving
      simvastatin. These results indicate that the development and progression of
      pulmonary hypertension is prevented by simvastatin by up-regulating GATA-6
      expression in the lung tissue.

PMID- 19842844
TI  - Infrequently methylated event at sites -181 to -9 within the 5' CpG island of E
      cadherin in non-small cell lung cancer.
AB  - Epigenetic silencing of E-cadherin via aberrant methylation has been investigated
      in various human tumors, whereas evidence for elucidating mechanism underlying
      reduction of E-cadherin mRNA remains unclear in non-small cell lung cancer
      (NSCLC). The authors previously found that reduction of E-cadherin mRNA or
      protein expression has been frequently observed in NSCLC. In this study, the
      authors explore the contribution of E-cadherin methylation to the development and
      progression of NSCLC. The authors directly performed the bisulfite DNA sequencing
      to examine CpG methylation within the 5' CpG island of E-cadherin in 35 tumor and
      paired normal tissue specimens from patients with primary NSCLC. Then, the
      authors measured the level of E-cadherin mRNA by real-time quantitative
      polymerase chain reaction (PCR) analysis. Despite of reduction in E-cadherin mRNA
      by 65.7% (23/35) and presence of methylation by 28.6% (10/35) in tumors, the
      authors found no association of reduction of E-cadherin mRNA level with
      methylation of 19 sites from -181 to -9 bp located upstream from the translation
      start of E-cadherin in NSCLC. In conclusion, the authors provide no evidence for
      the presence of aberrant methylation sites of E-cadherin in tumors from patients
      with NSCLC, which can explain decrease of E-cadherin mRNA. Decrease in E-cadherin
      mRNA may be regulated by methylation-independent pathways in NSCLC.

PMID- 19842846
TI  - Preexposure to repeated low doses of zymosan increases the susceptibility to
      pulmonary infection in rats.
AB  - Chronic exposure to low levels of mold has been reported to increase
      susceptibility to respiratory infections. In the current study, the authors
      investigate the lungs' ability to clear an infection after repeated low-dose
      zymosan exposure. Exposure was conducted at a zymosan dose of 0.6 mg/kg body
      weight (bw) of rat, for a total of 4 doses, via intratracheal instillation during
      a 2 week period. Treated animals were allowed to recover for 1 week before
      pulmonary inoculation with Listeria monocytogenes. Bacterial clearance was
      determined by measuring colony-forming units cultured from the left lungs on days
      3, 5, and 7 post bacteria infection. Bronchoalveolar lavage (BAL) was performed
      on the right lungs to recover phagocytes and BAL fluid to measure lung injury and
      the inflammatory cytokines. In contrast to the authors' previously published
      study that showed a single high dose (2.5 mg/kg bw) of zymosan prior to infection
      accelerated bacteria clearance, the repeated low-dose zymosan suppressed bacteria
      clearance from the lungs early after infection and induced higher lung injury and
      inflammation compared to control. The innate immune response was down-regulated
      and a Th2 immune response was preferentially induced rather than a Th1 response,
      the latter being more effective toward the resolution of a L. monocytogenes
      infection.

PMID- 19842845
TI  - Immune responses of airway neutrophils are impaired in asthma.
AB  - Neutrophilic inflammation is a key effector arm of the innate immune response.
      Neutrophils may contribute significantly to airway inflammation in certain asthma
      subtypes. The objective of this study is to investigate the innate immune
      responses of isolated airway and circulating neutrophils in asthma. Participants
      with asthma (n = 17) and healthy volunteers (n = 11) underwent induced sputum and
      blood collection. Neutrophils were isolated from dispersed selected sputum and
      blood granulocytes using magnetic cell separation. Neutrophils were cultured with
      or without lipopolysaccharide (100 ng/mL) for 24 hours. Innate immune mediators
      were measured by enzyme-linked immunosorbent assay (ELISA) and real-time
      polymerase chain reaction (PCR). Airway neutrophils from participants with asthma
      spontaneously released lower levels of interleukin (IL)-8, IL-1beta and tumor
      necrosis factor-alpha proteins, and had lower levels of cytokine gene expression
      compared to healthy controls. Toll-like receptor 4 (TLR4) gene expression was
      significantly decreased in airway neutrophils from participants with asthma
      compared to healthy volunteers. Resting and lipopolysaccharide (LPS)-stimulated
      circulating neutrophils had lower levels of TLR2 and IL-1beta gene expression in
      asthma, but were otherwise similar to healthy controls. No differences were seen
      for matrix metalloproteinase (MMP)-9 release in asthma. Innate immune responses
      of airway neutrophil cells are impaired in asthmatic subjects on prophylactic
      therapy and may impact on susceptibility to, and severity of, airway infections.

PMID- 19842847
TI  - Elevated endogenous surfactant reduces inflammation in an acute lung injury
      model.
AB  - Acute lung injury (ALI) is associated with severe pulmonary inflammation and
      alterations to surfactant, and often results in overwhelming systemic
      inflammation, leading to multiple organ failure. The objective of this study was
      to determine the effect of increased endogenous surfactant pools on pulmonary and
      systemic inflammation in a model of lipopolysaccharide (LPS)-induced ALI. Mice
      received an instillation of liposome-encapsulated (i) dichloromethylene
      diphosphonic acid (DMDP) to increase surfactant pools via depletion of alveolar
      macrophages, or (ii) phosphate-buffered saline (PBS). Seven days after
      instillation, mice received an intranasal administration of LPS or saline.
      Following a 4-hour recovery period, mice were sacrificed and their lungs were
      isolated, mechanically ventilated, and perfused with 8 mL of recirculated
      perfusate through the pulmonary circulation for 2 hours. Perfusate and lavage
      fluid were collected for analysis of inflammatory mediators. Lavage analysis
      revealed a 5-fold increase in surfactant pools in DMDP-treated mice compared to
      PBS-treated controls. Lavage and perfusate analyses showed significant decreases
      in the concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha,
      macrophage inflammatory protein (MIP)-1alpha, and IL-1beta cytokines in DMDP-LPS
      mice compared to PBS-LPS controls. Elevated endogenous surfactant pools are
      protective against both LPS- and mechanical ventilation-induced inflammation, in
      addition to inflammation associated with the combination of these two insults.

PMID- 19842848
TI  - Lack of soluble tumor necrosis factor alpha receptor 1 and 2 and interleukin
      1beta compartmentalization in lungs of mice after a single intratracheal
      inoculation with live Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis aspiration pneumonia induces local and systemic cytokine
      responses, but the dynamic of the immune response following lung exposure to live
      P. gingivalis is poorly understood. Groups of 50 12-week-old male BALB/c mice
      were inoculated intratracheally with live P. gingivalis ATCC 33277 using low dose
      (2 x 10(5) colony-forming units [CFU]), high dose (2.9 x 10(9) CFU), or phosphate
      buffered saline (PBS; sham-inoculated), and the 3 groups were sacrificed at 2, 6,
      24, 72, 168 hours. Lung and serum samples were collected for tumor necrosis
      factor alpha (TNF-alpha), soluble TNF-alpha receptors (sTNFRs), interleukin (IL)
      1beta, and IL-6 analysis and lung histology. Pneumonia, only observed in the high
      dose group, was associated with an early increase in lung TNF-alpha, IL-1beta,
      and IL-6, whereas no significant changes were observed in lung sTNFRs. Serum
      sTNFRs were significantly increased in high-dose animals at all times. IL-1beta
      elevation occurred earlier in serum than in lungs. IL-1beta was also
      significantly elevated in serum from low-dose animals at 6 hours. Serum IL-6 and
      sTNFRs remained raised at 7 days, whereas all other measured cytokines returned
      to basal levels with resolution of pneumonia. Development of pneumonia is
      dependent on the P. gingivalis dose; however, part of the cytokine response is
      unique to the systemic compartment, even in animals that do not develop
      pneumonia.

PMID- 19842849
TI  - Fixed-dose combination of cefepime plus amikacin (potentox) inhibits pneumonia
      infection.
AB  - Pneumonia is a severe infection that causes high morbidity and mortality rate
      worldwide. It is caused by Klebsiella pneumoniae, which generally causes upper
      respiratory tract infection. In case of such type of infection, levels of oxidant
      and antioxidant become imbalanced, which may contribute to lung injury. The
      present study was planned to evaluate the status of oxidant and antioxidant
      enzyme activities in plasma and lung tissue of pneumonia-infected rats model.
      Animals were randomly distributed into 3 groups of 8 rats each: groups I
      (control, normal saline treated), II (infected group), and III (infected +
      treated group). The findings showed that there was significant increase (P <
      .001) in body temperature along with decreased body weight in the infected group
      as compared to the control group. Similarly, all the activities of antioxidant
      enzymes (superoxide dismutase [SOD], catalase) were significantly decreased along
      with increased malonaldialdehyde (MDA) levels in plasma and lung tissue of the
      infected group as compared to the control group. These enzyme activities along
      with MDA levels were improved and came back near to normal level after
      administration of cefepime plus amikacin (potentox) for 7 days in group III.
      These studies concluded that fixed-dose combination of potentox improved oxidant
      and antioxidant levels in pneumonia infection.

PMID- 19842850
TI  - Responses of the European flounder Platichthys flesus to the chemical stress in
      estuaries: load of contaminants, gene expression, cellular impact and growth
      rate.
AB  - European flounder responses to the chemical stress were assessed by a comparative
      approach on four estuaries displaying contrasted patterns of contamination. The
      contamination typology of the estuaries was investigated by individual
      measurements of contaminants in fish. Molecular and physiological responses were
      studied by gene expression, genotoxicity, neurotoxicity and growth rate. Fishes
      in contaminated estuaries were characterized by high levels of bioaccumulated
      contaminants, slow energetic metabolism and reduced growth rate, in contrast to
      the fish responses in the reference site. A seasonal effect was highlighted for
      contaminated flounder populations, with high PCB levels, high genotoxicity and
      elevated detoxification rate in summer compared with winter.

PMID- 19842851
TI  - Focusing on function.

PMID- 19842852
TI  - Motor development of infants with positional plagiocephaly.
AB  - Concurrent with recommendations to place infants to sleep in supine, there has
      been a dramatic increase in the number of infants with positional plagiocephaly
      (PP). Recent evidence suggests that infants who have decreased exposure to prone
      position may have a higher incidence of PP and may be at risk for a delay in the
      acquisition of certain motor skills. The purpose of this study was to compare
      motor development between infants with PP and matched peers without PP. We also
      examined differences in infant positioning practices when asleep and awake
      between the two groups. Twenty-seven infants with PP, 3 to 8 months of age, were
      matched by age, gender, and race to infants without PP. Motor performance was
      evaluated using the Alberta Infant Motor Scale (AIMS) and the Peabody
      Developmental Motor Scales (PDMS). Parents completed a diary that recorded infant
      positioning over a 3-day period. Mean AIMS percentile score for infants with PP
      was 31.1 +/- 21.6 as compared with 42.7 +/- 20.2 in infants without PP (p = .06).
      Better performance on the AIMS was positively correlated with the amount of time
      in prone position when awake, for both groups of children (PP r = .52, no PP r =
      .44, p < .05). Therapists should be aware of a risk of a motor delay when
      evaluating infants with PP. It is also important for parents to be informed about
      the importance of supervised prone playtime to enhance the development of early
      motor skills.

PMID- 19842853
TI  - Supporting early development of infants with identified positional plagiocephaly.

PMID- 19842854
TI  - Sensory motor and functional skills of dizygotic twins: one with Smith-Magenis
      syndrome and a twin control.
AB  - Smith-Magenis syndrome (SMS), the result of an interstitial deletion within
      chromosome 17p11.2, is a disorder that may include minor dysmorphic features,
      brachydactyly, short stature, hypotonia, speech delays, cognitive deficits, signs
      of peripheral neuropathy, scoliosis, and neurobehavioral problems including sleep
      disturbances and maladaptive repetitive and self-injurious behaviors. Physical
      and occupational therapists provide services for children who have the syndrome,
      whose genetic disorder is frequently not identified or diagnosed before 1 year of
      age. A comprehensive physical and occupational therapy evaluation was completed
      in nonidentical twins with one having SMS, using the Sensory Profile; Brief
      Assessment of Motor Function (BAMF); Peabody Developmental Motor Scales, Second
      Edition (PDMS-2); and Pediatric Evaluation of Disability Inventory (PEDI). This
      provides a framework for conducting assessments to enhance early detection and
      interdisciplinary management with this specialized population.

PMID- 19842855
TI  - Household task participation of children with and without attentional problems.
AB  - Children with attention deficit/hyperactivity disorder (ADHD) often demonstrate
      problems in their participation in family occupations, such as household tasks,
      due to their needs for assistance and their behavior. Because participation in
      household tasks is part of family life and may be one way that families prepare
      children for adult roles, it is important to have a better understanding of the
      nature and extent of these difficulties. Forty-four parents of children in grades
      three through five (22 who had a child with ADHD and 22 whose child had no
      disabilities) completed the Children Helping Out: Responsibilities, Expectations,
      and Supports (CHORES) measure to provide quantitative and qualitative information
      about their child's participation in household tasks. Children with ADHD did not
      differ significantly from the comparison group in their frequency of
      participating in household tasks. Children with ADHD, however, required
      significantly more assistance with the tasks than did the comparison group. The
      results have implications for family occupations and children's occupational
      development.

PMID- 19842856
TI  - Factors associated with participation of children with and without ADHD in
      household tasks.
AB  - Children's preparation for adult roles and independent living occur largely
      through participation with their families in home routines including household
      tasks. This preparation may involve learning related to family roles,
      socialization, and occupational performance. This study was designed to explore
      the extent to which child, environmental, and task factors are associated with
      household task participation by school-aged children, 9 to 11 years of age, with
      and without attention deficit/hyperactivity disorder (ADHD). Forty-four parents
      of children with and without ADHD completed a series of measures that examined
      family routine frequency and importance, parenting stress, parenting sense of
      competence, and a measure of their children's participation in household tasks.
      Child's age, the presence of an older sibling, and the importance of family
      routines were significant predictors of the number of household tasks performed
      by children. Diagnosis of ADHD, the presence of an older sibling, and parental
      stress were significant predictors of the amount of assistance the children
      required to do the household tasks.

PMID- 19842857
TI  - The Participation in Childhood Occupations Questionnaire (PICO-Q): a pilot study.
AB  - There is a need, among practitioners and researchers, for a feasible, user
      friendly assessment tool that evaluates overall participation and guides
      intervention. This paper describes the process of construction and development of
      the Participation in Childhood Occupations Questionnaire (PICO-Q) and the
      establishment of its primary psychometric properties. The 22-item instrument
      measures the level, enjoyment, and frequency of performance for children's
      participation in daily occupations in a variety of environments. The
      questionnaire was completed by the mothers of 41 children between the ages of 6
      and 10 years (24 children with and 17 children without sensory modulation
      disorder). Cronbach's alpha varied from. 86 to. 89, indicating internal
      consistency of items. Test-retest reliability varied from. 69 to. 86, indicating
      that the instrument provides a stable measurement over time. The PICO-Q was found
      to differentiate between children with and without participation restrictions.
      The PICO-Q shows initial reliability and validity and has both research and
      clinical application potential.

PMID- 19842858
TI  - Feasibility of a day-camp model of modified constraint-induced movement therapy
      with and without botulinum toxin A injection for children with hemiplegia.
AB  - The objective of the study was to investigate the feasibility of modified
      constraint-induced (CI) therapy provided in a 2-week day-camp model with and
      without intramuscular botulinum toxin type A (BoNT-A) injections for children
      with congenital cerebral palsy. Sixteen children with congenital hemiplegia,
      Manual Ability Classification System (MACS) level I and II, aged 8-17 years,
      participated in a CI therapy day camp; of whom five participants (aged 11-16
      years) received intramuscular BoNT-A prior to CI therapy. Assessments were
      conducted 4 months and 2 weeks before (baselines 1 and 2), immediately after, and
      6 months after the day camp. For the children who received BoNT-A, no statistical
      analyses were conducted due to the small size of the sample. In this group,
      consistent improvement was only found according to the Melbourne Unilateral Limb
      Assessment. The children who received only the CI therapy demonstrated
      improvements in the Jebsen-Taylor Hand Function Test (p =. 04) at posttest, but
      improvements were not sustained at 6-month follow-up. No significant improvement
      was obtained for the Melbourne Assessment or the Assisting Hand Assessment.
      Children in both groups improved on specially trained tasks: frisbee golf,
      stacking blocks, and in-hand manipulation. Feedback from the participants
      suggests that the day-camp model is a feasible intervention following
      intramuscular BoNT-A injections. The results suggest that children with
      congenital hemiplegia with varying severity of impairment in hand function may
      benefit from CI therapy, but not every child demonstrates improvements in hand
      function. The characteristics of children who respond the best to CI therapy are
      not clear.

PMID- 19842861
TI  - Physical Therapy Practice in the 21st Century: A New Evidence-informed Paradigm
      and Implications'. Foreword from the special issue editor.

PMID- 19842862
TI  - Physical therapy in the 21st century (Part I): toward practice informed by
      epidemiology and the crisis of lifestyle conditions.
AB  - Part I of this two-part introduction to this Special Issue on the practice of
      physical therapy in the 21st century outlines the epidemiological basis and
      rationale for evidence-informed physical therapy practice for addressing
      contemporary health priorities. This evidence emanates from the definition of
      health by the World Health Organization (WHO) and the International
      Classification of Functioning (ICF), and WHO and other international databases on
      the prevalence of lifestyle conditions. Lifestyle conditions include ischemic
      heart disease, smoking-related conditions, hypertension and stroke, obesity,
      diabetes, and cancer. Epidemiological data combined with evidence supporting the
      effectiveness of noninvasive interventions related to physical therapy to address
      these priorities (e.g., health education and exercise) are highly consistent with
      the promotion of health and wellness and the ICF. Given their commitment to
      exploiting effective noninvasive interventions, physical therapists are in a
      preeminent position to focus on prevention of these disabling and lethal
      conditions in every client or patient, their cure in some cases, as well as their
      management. Thus, a compelling argument can be made that clinical competencies in
      21st century physical therapy need to include assessment of smoking and smoking
      cessation (or at least its initiation), basic nutritional assessment and
      counseling, recommendations for physical activity and exercise, stress assessment
      and basic stress reduction recommendations, and sleep assessment and basic sleep
      hygiene recommendations. The physical therapist can then make an informed
      clinical judgment regarding whether a client or patient needs to be referred to
      another professional related to one or more of these specialty areas. The
      prominence of physical therapy as an established health care profession and its
      unique pattern of practice (prolonged visits over prolonged periods of time)
      attest further to the fact that physical therapists are uniquely qualified to
      lead in the assault on lifestyle conditions. Evidence-based physical therapy
      practiced within the context of epidemiological indicators (i.e., evidence
      informed practice) maximally empowers clinicians to promote lifelong health in
      every person and in turn, the health of communities. This vision of physical
      therapy's leading role in health promotion and health care in the 21st century
      holds the promise of reducing the need for invasive health interventions (drugs
      and surgery). Part II of this introduction describes evidence-based physical
      therapy practice within this context of evidence-informed practice.

PMID- 19842863
TI  - Physical therapy in the 21st century (Part II): evidence-based practice within
      the context of evidence-informed practice.
AB  - Part II of this two-part introduction to this Special Issue on physical therapy
      practice in the 21st century outlines a health-focused strategy for physical
      therapists to lead in the assault on lifestyle conditions, global health care
      priorities, described in Part I. Consistent with contemporary definitions of
      physical therapy, its practice, professional education, and research, physical
      therapy needs to reflect 21st-century health priorities and be aligned with
      global and regional public health strategies. A proposed focus on health
      emphasizes clinical competencies, including assessments of health, lifestyle
      health behaviors, and lifestyle risk factors; and the prescription of
      interventions to promote health and well-being in every client or patient. Such
      an approach is aimed to increase the threshold for chronic conditions over the
      life cycle and reduce their rate of progression, thereby preventing, delaying, or
      minimizing the severity of illness and disability. The 21st-century physical
      therapist needs to be able to practice such competencies within the context of a
      culturally diverse society to effect positive health behavior change. The
      physical therapist is uniquely positioned to lead in health promotion and
      prevention of the lifestyle conditions, address many of their causes, as well as
      manage these conditions. Physical therapists need to impact health globally
      through public and social health policy as well as one-on-one care. This role is
      consistent with contemporary definitions of physical therapy as the
      quintessential noninvasive health care practitioner, and the established efficacy
      and often superiority of lifestyle and lifestyle change on health outcomes
      compared with invasive interventions, namely, drugs and surgery. A concerted
      commitment by physical therapists to health and well-being and reduced health
      risk is consistent with minimizing the substantial social and economic burdens of
      lifestyle conditions globally.

PMID- 19842864
TI  - Advice as a smoking cessation strategy: a systematic review and implications for
      physical therapists.
AB  - Although identified as a clinical priority, smoking cessation has been addressed
      minimally in the literature in the context of physical therapy practice. Smoking
      cessation advice delivered by a health professional can help smokers quit. The
      salient components of such advice however warranted elucidation to enable
      physical therapists to integrate this clinical competence into their practices.
      Therefore, we conducted a systematic review to elucidate the effectiveness of
      advice by a health professional and its components to optimize smoking cessation
      instituted in the context of physical therapy practice. Thirty source articles
      were identified. A random-effects model meta-analysis was used to assess the
      effectiveness of the advice parameters. Risk ratios (RRs) were used to estimate
      pooled treatment effects. RRs for brief, intermediate, and intensive advice were
      1.74 (95% CI=1.37, 2.22), 1.71 (95% CI=1.39, 2.09), and 1.60 (95% CI=1.13, 2.27),
      respectively. Self-help materials, follow-up, and interventions based on
      psychological or motivational frameworks were particularly effective components
      of intermediate and intensive advice interventions. Advice can be readily
      integrated into physical therapy practice and used to initiate or support ongoing
      smoking cessation in clients irrespective of reason for referral. Incorporating
      smoking cessation as a physical therapy goal is consistent with the contemporary
      definition of the profession and the mandates of physical therapy professional
      associations to promote health and wellness, including smoking cessation for both
      primary health benefit and to minimize secondary effects (e.g., delayed healing
      and recovery, and medical and surgical complications). Thus, advice is an
      evidence-based strategy to effect smoking cessation that can be exploited in
      physical therapy practice. Further research to refine how best to assess smokers
      and, in turn, individualize brief smoking cessation advice could augment positive
      smoking cessation outcomes.

PMID- 19842865
TI  - Strategies for optimizing nutrition and weight reduction in physical therapy
      practice: the evidence.
AB  - Poor nutrition and obesity can directly lead to pathological conditions managed
      by physical therapists or negatively influence recovery from movement
      dysfunction. The physical therapist/client relationship provides an opportunity
      for screening for poor nutrition as well as recommending and supporting better
      nutrition practices by the clients under their care. As such, it is important for
      the physical therapy professional to understand optimal nutrition for healthy
      living and serve as a consultant for better nutrition for their clients. To
      achieve this end, this article addresses strategies for identifying nutritional
      trends for the specific groups of clients, screening for nutritional problems,
      assessing clients' readiness to change eating habits, providing useful
      information and resources concerning optimal nutrition, and recognizing the need
      for referral to nutrition professionals.

PMID- 19842866
TI  - Building motivation and sustainability into the prescription and recommendations
      for physical activity and exercise therapy: the evidence.
AB  - Client adherence to exercises prescribed by a physical therapist is very
      important to successful treatment outcomes. Unfortunately, many clients struggle
      with adherence and thus efficient and effective motivational interventions are
      desirable. The purpose of this article was to review the available evidence for:
      1) the modifiable factors associated with adherence to physical therapy
      recommended exercise and 2) the efficacy of exercise intervention efforts to make
      conclusions and suggestions toward practice. Articles were limited to English
      peer-reviewed journals and published from 1993 to 2008. Major findings from 13
      studies were summarized based on common subtopics of: outcome expectations, self
      efficacy expectations, cognitive-behavioural and educational interventions, and
      intervention medium. The review provided evidence for the importance of self
      efficacy in exercise adherence to physical therapy, but it showed that current
      cognitive-behavioural interventions have had limited effectiveness. It was
      recommended that future research broaden the scope of predictor variables with
      social ecological designs, increase the length of prospective follow-up in
      assessments, include larger and more diverse samples, and focus on innovative
      aesthetic and affective-based intervention strategies.

PMID- 19842867
TI  - Sleep health and its assessment and management in physical therapy practice: the
      evidence.
AB  - Sleep and sleep deprivation have become major health issues in our modern
      society. Impaired sleep can negatively affect physical and psychological well
      being, and conversely, certain common conditions can impair sleep. Furthermore,
      insufficient or disrupted sleep can contribute to functional impairments. As
      health care professionals, physical therapists are singularly concerned with
      function and well-being. To understand the role of sleep and sleep deprivation on
      health, this article describes sleep, our contemporary culture of sleeplessness,
      insomnia, sleep needs, the physical cost of inadequate sleep, the psychological
      cost of sleep deprivation, and the effects of sleep debt on safety. How to assess
      an individual's sleep debt is then described, and a sleep inventory questionnaire
      and scoring scale are presented. Evidence-based recommendations for optimizing
      sleep are outlined, and these can be readily implemented by the busy clinician.
      The sleep inventory questionnaire can be used to evaluate the outcome of these
      recommendations or other interventions as well as serve as an assessment tool.
      Based on the literature, the assessment and evaluation of sleep and basic sleep
      recommendations need to be considered as fundamental clinical competencies in
      contemporary physical therapy care.

PMID- 19842868
TI  - Psychological Stress Measure (PSM-9): integration of an evidence-based approach
      to assessment, monitoring, and evaluation of stress in physical therapy practice.
AB  - Stress can be a primary or secondary contributor to ill health via excessive and
      sustained sympathetic arousal leading to ischemic heart disease, hypertension,
      stroke, obesity, and mental ill health, or through related behaviors such as
      smoking, substance abuse, and over or inappropriate eating; or as a contextual
      variable in terms of risk factor and lifestyle outcome. In addition, psychosocial
      stress can impair recovery from any pathological insult or injury. Most
      assessments of stress relate to life events, and both past and current life
      stressors, acute and chronic, play a major role. However, beyond the impact of
      stressors, it is the reported state of feeling stressed that is the critical
      predictor of ill health. This article describes stress and its correlates,
      discusses models of stress, and presents the nine-item Psychological Stress
      Measure (PSM-9). This tool is aimed directly at the state of feeling stressed, is
      suited for assessing stress clinically in the general population and serving as
      an outcome measure. The tool is valid and reliable and easy to administer in
      health care settings; it has a normal distribution, which makes it a very
      sensitive-to-change instrument in repeated measures to document progress.

PMID- 19842869
TI  - Cystic lung disease in infants and children.
AB  - Cysts within the lung are one of the more common pulmonary pathological findings
      seen in an active pediatric surgical pathology service. Of both developmental and
      acquired origin, they may present as respiratory distress in infants or may be
      asymptomatic lesions incidentally discovered by images studies of the thoracic
      for "non-pulmonary" reasons. The most frequently seen developmental cysts of the
      lung are those of Congenital Pulmonary Airway Malformations, types 1, 2 & 4.
      Other congenital cystic lesions include bronchogenic cysts (usually in older
      patients) and some of the enteric duplication lesions that contain cysts.
      Acquired cystic lung lesions include acute and persistent pulmonary interstitial
      emphysema, postinfarction peripheral cysts, postinfectious pulmonary cysts, and
      the cystic form of pleuropulmonary blastoma.

PMID- 19842870
TI  - Neuroblastoma in a patient with Coffin-Siris syndrome.
AB  - We report the case of an 8-year-old boy with the phenotypic features of Coffin
      Siris syndrome diffuse hypertrichosis, flat occiput, scant scalp hair, flat
      supraorbital arch, triangular eyebrows, horizontal palpebral fissure, anteverted
      nares, triangular philtrum, coarse lips, high-arched palate, micrognathia, low
      set and dorsaly rotated ears, short neck, wide thorax, widely set nipples,
      transverse palmar crease, psychomotor delay, urinary malformations (paraurethral
      diverticulum, hypoplasia of left kidney associated with vesicoureteral reflux
      grade 3-4), bilateral inguinal hernia, and dorsolumbar kyphoscoliosis. In the
      follow-up he presented a retroperitoneal neuroblastoma. Although this type of
      tumor has been referred to develop in several genetic and mutimalformative
      syndromes, it seems that present association has not been previously reported.

PMID- 19842871
TI  - Pulmonary lobar interstitial emphysema.
AB  - Pulmonary interstitial emphysema is a relatively common entity in neonatal
      intensive care units. It can occur in full-term babies but more frequently occurs
      in premature infants receiving positive pressure ventilation. The process can be
      localized or diffuse, and the diagnosis is based on the presence of air in the
      interstitial pulmonary tissue, observed by radiology. The localized form is more
      rare and one or more lobes may be involved in the process. Our case report is of
      a second twin male, born after 33 weeks of gestation. After birth, a mild
      respiratory distress was installed, and the patient was treated with nasal
      continuous positive airway pressure. After two pneumothoraces, an image of
      diffuse cystic changes was observed in the right upper lobe. The patient was
      operated with the clinical and radiologic diagnosis of cystic adenomatoid
      malformation. The histological study of the resected lobe, by light and scanning
      electron microscopy, revealed a localized pulmonary interstitial emphysema.

PMID- 19842874
TI  - Lumbosacral Wilms' tumor as a component of immature teratoma associated with
      spinal dysraphism--a rare case and short literature review.
AB  - Occurrence of extrarenal Wilms' tumor, in the lumbosacral region, as such or as a
      component of immature teratoma is an extremely uncommon condition and this
      diagnosis is almost always postsurgical. We report a case of immature teratoma in
      the lumbosacral region which was composed of mature teratomatous components and
      Wilms' tumor as an immature component. This 20-day-old male child presented with
      a swelling over the lower back at birth. Imaging of the spine revealed spina
      bifida and tethered cord. Excision of soft tissue swelling and detethering of the
      cord was performed. This case represents the fourth reported case of lumbosacral
      Wilms' tumor as a component of immature teratoma associated with spinal
      dysraphism. We discuss possible mechanisms and clinical characteristics of
      extrarenal Wilms' tumor and present a short review of the literature.

PMID- 19842875
TI  - Calcified cystic lymphangioma of the mesentery: case report.
AB  - Mesenteric cysts are rare and are associated with heterogeneous pathological
      conditions. We describe an extraordinary case of mesenteric calcified cystic
      lymphangioma in a 10-year-old boy. To the best of our knowledge only 6 mesenteric
      calcified cystic lymphangioma have been reported. The patient was admitted with
      abdominal pain and vomiting. Abdominal X-ray and computed tomography scan
      documented a calcified cyst which dislocated and compressed the ileum. Laparatomy
      revealed that the cyst arose in the mesentery at 100 cm from the ileocecal valve.
      The cystic wall was composed of fibrosclerotic calcified tissue and had an
      endothelial lining. In the adjacent fibrofatty stroma there were distended
      hemolymphatics. Postoperative recovery was uneventful. At follow-up 6 months
      after surgery the patient is well. Calcified cystic lymphangioma of the mesentery
      should be considered in the differential diagnosis of an intra-abdominal
      calcified cyst in children.

PMID- 19842876
TI  - Massive pericardial effusion treated with in utero pericardioamniotic shunt in a
      fetus with intrapericardial teratoma.
AB  - Teratoma is the leading neoplasm diagnosed in neonates and infants. Although over
      99% of teratomas found in the fetus and newborn are histologically benign, those
      tumors may cause death if vital structures are involved or if the airway is
      compromised. We review the literature on antenatal intrapericardial teratomas and
      report a case of intrapericardial teratoma, with massive pericardial effusion and
      fetal hydrops, diagnosed on antenatal ultrasound at 21 weeks of gestation.
      Pericardioamniotic shunt was placed at 22 weeks and 6 days gestational age. In
      spite of successful drainage of the pericardial effusion, fetal demise was
      documented 8 days later, likely due to tumor compression of the heart.

PMID- 19842877
TI  - Aromatase may play a critical role in the pathogenesis of juvenile nasopharyngeal
      angiofibroma.
AB  - The pathophysiology of juvenile nasopharyngeal angiofibroma (JNA) has yet to be
      fully elucidated, but the influence of steroid hormones in their growth has been
      suggested. This neoplasm is known to afflict adolescent males. However, only a
      minority of the neoplastic cells express androgen receptors. The expression of
      estrogen receptor beta by the tumor cells recently has been demonstrated.
      Aromatase (P450) is an enzyme which is responsible for converting androgens to
      estrogens. However, the rule of aromatase in the pathogenesis of JNA is unknown.
      In this study we attempt to explain the hormone-induced growth theory by
      characterizing the aromatase (P450) in JNA. We examined five sinonasal JNA from
      adolescent males, all of which stained positive for aromatase. We propose that
      this enzyme is responsible for the local conversion of androgens into estrogens,
      which subsequently bind to the estrogen receptors leading to the growth of these
      tumors.

PMID- 19842878
TI  - Fetal umbilical cord blood erythropoietin, interleukin-6, pH, pO(2), pCO(2), and
      base excess levels in histologic and/or clinical chorioamnionitis: is the
      response only inflammatory?
AB  - OBJECTIVE: To determine the correlation of histological chorioamnionitis (CA)
      with and without clinical CA with umbilical cord blood gases, erythropoietin
      (EPO), and interleukin-6 (IL-6) levels. METHODS: Umbilical artery blood gas
      analysis (pH, pO(2), pCO(2), BE) and umbilical vein EPO and IL-6 levels were
      measured in 202 infants from normal, histological, and no clinical CA and
      histological plus clinical CA pregnancies. RESULTS: Umbilical artery blood gas
      analyses were not different between normal controls and histological and clinical
      CA groups. Blanc Stage 1 histological CA had no abnormal EPO or IL-6 umbilical
      blood results. EPO in umbilical venous blood was elevated only in those infants
      with both histological and clinical CA. Umbilical vein IL-6 levels were elevated
      in all advanced microscopic and clinical CA. High and low EPO groups also have
      corresponding high and low IL-6 levels suggesting a common stimulus for these
      substances. CONCLUSIONS: Blanc stage I histological CA is probably clinically
      insignificant. CA is infrequently associated with abnormal umbilical artery blood
      gas levels. Advanced histological and clinical CA can elevate both EPO and IL-6
      in umbilical blood and these may be key elements of mechanisms that effect fetal
      brain function.

PMID- 19842879
TI  - Extreme variant of enlarged heterochromatin region on chromosome 9Q in a normal
      child and multiple family members.
AB  - Heteromorphisms of chromosome 9 are among the most common variations in the human
      karyotype. The pericentromeric polymorphisms of chromosome 9 include variations
      in the size of q-arm heterochromatin, pericentric inversions, and rarely,
      additional C-band-negative, G-band-positive material. The finding of a
      polymorphic variant, either in prenatal screening or in chromosomal analysis for
      phenotypic abnormalities, may cause parental anxiety and initiate genetic
      counselling. We report a case of a 39-year-old primigravida with unremarkable
      pregnancy, who had amniocentesis due to advanced maternal age. Chromosomal
      analysis demonstrated a long arm (q) variant of chromosome 9 with an enlarged
      heteromorphic area, approximately three times longer than known reported
      variants. Prenatal analysis demonstated an identical variant in the probands
      phenotypically normal father, uncle, and paternal grandmother, confirming an
      apparently "normal" variant.

PMID- 19842880
TI  - Prenatal diagnostic accuracy in South Carolina demonstrated by autopsy.
AB  - Fully 150 consecutive fetal/neonatal autopsies were reviewed to determine to what
      extent they confirmed or altered the impressions gained through prenatal
      ultrasonographic fetal examination. Distinctions were made between features that
      may or may not be assessable by prenatal ultrasound. Analyses of weights and
      measures were based on recently published regressions derived from a worldwide
      review of normative data. Our analysis indicated a high level of correspondence
      between prenatal ultrasound findings and later observations of independent
      persons at autopsy (85% positive predictive value and 44% sensitivity). We
      concluded that skills of maternal-fetal medicine specialists, located at several
      geographically divergent centers, are confirmed by a high level of correspondence
      between prenatal ultrasound and autopsy findings. The low sensitivity was due in
      large part to the relatively subtle nature of many autopsy findings that had not
      been predicted by prenatal examination.

PMID- 19842881
TI  - Thirteen-year-old child with a malignant chest tumor: clinicopathologic
      conference.
AB  - A case of pleuropulmonary blastoma in a 13-year-old child, exposed to the
      Chernobyl disaster while in-utero, is presented and discussed by both clinician
      and pathologist, in this traditional clinical-pathologic conference. The
      discussion includes the differential diagnoses of chest mass in children.

PMID- 19842882
TI  - Stillborn infant with calcified chorionic epithelium, corneal scarring, and
      pericarditis.
AB  - This autopsy of a stillborn term infant revealed a constellation of unusual
      features including calcification of the chorion membrane and portions of the
      umbilical vascular media, extensive white matter gliosis, arthrogryposis
      multiplex congenita, adhesions of one eyelid to the globe, pericarditis, a
      miniature left foot, and a cleft palate. We hypothesized that the membrane and
      umbilical cord lesions resulted from an episode of resolved chorioamnionitis
      earlier in the pregnancy. Mare reproductive loss syndrome (MRLS) demonstrates a
      bacteremic infection of the amniotic cavity, pericarditis, and uniocular
      endophthalmitis in the mare. On the basis of analogy, we speculated that this
      infant suffered an intrauterine bacteremia with tissue predilection similar to
      that of MRLS.

PMID- 19842885
TI  - Importance of medical and surgical research.
AB  - Research is the keystone on the advancement of medicine and surgery. It is not
      possible to progress in any medical and/or surgical discipline without the
      contributions of research. Research is at the forefront of patient care whether
      medical or surgical. Centuries of creative research have opened the doors to new
      medical and surgical frontiers that before would not have been feasible. Medical
      and surgical sciences would not have climbed to the heights we know today without
      the perseverance and insistence of research. Research has been the driving force
      introducing new directions on the improvement of medicine and surgery.

PMID- 19842883
TI  - Discordant omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex
      and cardiac malformations in monochorionic twins.
AB  - The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex was
      first described by Carey et al. in 1978. It constitutes a specific combination of
      malformations. There are very few case reports of discordant OEIS in monozygotic
      twins and very few reports of OEIS in association with both hypoplastic left
      heart and ventricular septal defect. Our case represents the fifth reported case
      of cardiac malformations in a fetus with OEIS complex.

PMID- 19842886
TI  - X-rays surgical revolution.
AB  - Wilhelm Roentgen (1845-1923) created a surgical revolution with the discovery of
      the X-rays in late 1895 and the subsequent introduction of this technique for the
      management of surgical patients. No other physician or scientist had ever
      imagined such a powerful and worthwhile discovery. Other scientists paved the way
      for Roentgen to approach the use of these new X-rays for medical purposes. In
      this way, initially, and prior to Roentgen, Thompson, Hertz, and Lenard applied
      themselves to the early developments of this technology. They made good advances
      but never reached the clearly defined understanding brought about by Roentgen.
      The use of a Crookes tube, a barium platinocyanide screen, with fluorescent light
      and the generation of energy to propagate the cathode rays were the necessary
      elements for the conception of an X-ray picture. On November 8, 1895, Roentgen
      began his experiments on X-ray technology when he found that some kind of rays
      were being produced by the glass of the tube opposite to the cathode. The
      development of a photograph successfully completed this early imaging process.
      After six intense weeks of research, on December 22, he obtained a photograph of
      the hand of his wife, the first X-ray ever made. This would be a major
      contribution to the world of medicine and surgery.

PMID- 19842887
TI  - Ventilation during cardiopulmonary bypass: impact on neutrophil activation and
      pulmonary sequestration.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) is associated with neutrophil
      activation, pulmonary sequestration, and release of inflammatory mediators
      leading to pulmonary dysfunction. We investigate the effect of continuous
      ventilation during cardiopulmonary bypass on neutrophil activation and pulmonary
      sequestration. METHODS: Forty-six patients undergoing coronary artery bypass
      grafting with cardiopulmonary bypass were prospectively randomized to continuous
      ventilation and nonventilation groups. Blood samples were collected, and
      bronchoalveolar lavage (BAL) was performed following induction of anesthesia and
      at 4 hr after aortic declamping. Differential white cell count was measured, and
      flow cytometry to determine cell count numbers and quantify CD45 and CD11b
      leukocyte cell surface adhesion molecule expression was performed on the blood
      and BAL samples. RESULTS: Twenty-three patients were randomized to standard
      nonventilated CPB and 23 patients to ventilation throughout CPB. Significant
      increases in blood and BAL neutrophil numbers were detected at 4 hr following
      aortic declamping in both groups (Blood: NV p < .0001, V p < .0001; BAL: NV p =
      .017, V p = .0007). No significant inter-group differences in BAL and blood
      neutrophil numbers were found. Significantly higher blood neutrophil CD11b mean
      fluorescent intensity levels were present 4 hr following declamping compared with
      baseline in both groups (NV Blood, p = .021; V Blood p < .0001). No significant
      inter- or intragroup differences in BAL neutrophil CD11b mean fluorescent
      intensity levels were found. There was no death or major complication.
      CONCLUSIONS: Cardiopulmonary bypass during coronary artery bypass grafting is
      associated with increased neutrophil pulmonary sequestration, and blood
      neutrophil CD11b activation. Continuous ventilation during cardiopulmonary bypass
      does not significantly reduce neutrophil pulmonary sequestration or activation.

PMID- 19842888
TI  - Evaluation of a modified HTK solution containing the new iron chelator LK 614 in
      an isolated rat liver perfusion model.
AB  - BACKGROUND: Cold storage-induced injury to donor organs remains a persistent
      problem in transplantation medicine. We here evaluated a modified HTK solution
      including, among others, a new, membrane-permeable iron chelator, LK 614, in the
      isolated perfused rat liver model. METHODS: Rat livers were stored at 4 degrees C
      for 24 hr in modified HTK solution, in modified HTK solution with LK 614 or in
      traditional HTK solution, and reperfused for 60 min at 37 degrees C with Krebs
      Henseleit buffer (KH buffer). Bile secretion and lactate dehydrogenase (LDH)
      release into the perfusate were measured, and hepatic microcirculation evaluated
      optically after the addition of trypan blue to the perfusate. Biopsies were
      evaluated by a pathologist blinded to the experimental conditions. RESULTS:
      Compared with HTK-preserved livers, LDH leakage was significantly lower and bile
      secretion significantly higher in the modified HTK solution with the iron
      chelator (both p < .05), while values for the modified solution without the iron
      chelator were in between (no significant difference to either of the two other
      solutions). The hepatic microcirculation was also preserved best in livers stored
      in the modified HTK solution with LK 614. Histomorphological investigation
      confirmed the improved preservation in the modified HTK solution with LK 614.
      CONCLUSIONS: These results suggest that livers might be better preserved in
      modified HTK solution containing the iron chelator LK 614 (and also, but less so,
      in the modified solution without the iron chelator) than in the original HTK
      solution, and such a modified solution should now be evaluated in an animal model
      of liver transplantation.

PMID- 19842889
TI  - Propofol with N-acetylcysteine reduces global myocardial ischemic reperfusion
      injury more than ketamine in a rat model.
AB  - OBJECTIVE: We examined the cardioprotective effects of propofol and ketamine with
      and without N-acetylcysteine (NAC). METHODS: 60 rats were divided into six groups
      of 10 rats each. Anesthesia induction was produced with an intraperitonal
      injection of ketamine in Groups 1-3 and propofol in Groups 4-6. NAC (200 mg kg(-
      1)) was given intraperitonally during anesthesia induction in Groups 3 and 6.
      Groups 2, 3, 5, and 6 were subjected to 90 s of myocardial ischemia by clamping
      the ascending aorta, and then reperfusion was begun by unclamping the ascending
      aorta. After 60 min of reperfusion, blood samples were taken from the ascending
      aorta for biochemical analyses, and heart tissue samples were taken for
      biochemical and histopathological analyses. RESULTS: Creatine kinase (CK),
      myocardial band of creatine kinase (CK-MB), and troponin-I (Tn-I) levels were
      significantly higher in the ischemia-reperfusion groups (2, 3, 5, 6) compared to
      the nonischemic groups (1, 4). CK, CK-MB, and Tn-I levels did not differ
      significantly between the ketamine groups (1-3) and the propofol groups (4-6) p >
      .05). Malondialdehyde levels were significantly higher in Groups 2 and 3 than in
      Group 1 and were significantly lower in Groups 4 and 6 than in Group 5 (p < .05).
      Malondialdehyde levels in the propofol groups (4-6) were significantly lower than
      in the ketamine groups (1-3; p < .05). Catalase levels in propofol groups were
      higher than ketamine groups. Superoxide dismutase levels were significantly
      higher in Group 6 than in Group 3 (p < .05). CONCLUSIONS: In this rat model of
      global cardiac ischemia, propofol with NAC attenuates myocardial injury more than
      ketamine (with or without NAC).

PMID- 19842890
TI  - The effects of resveratrol on the healing of left colonic anastomosis.
AB  - INTRODUCTION: Resveratrol (RSV) is a natural polyphenolic compound found in grape
      skins and the red wine which improves histological reorganization of the
      regenerating tissue in dermal wound healing. Since anastomotic healing possesses
      paramount importance to prevent complications in colorectal surgery, the present
      study is aimed to evaluate the effect of RSV on the healing of experimental left
      colonic anastomoses. METHODS: Thirty-two male Wistar albino rats were randomized
      into two groups and subjected to colonic anastomosis. The study group was treated
      with RSV and the control group received tap water instead. The rats were
      sacrificed 3 and 7 days postoperatively. Wound complications, intra-abdominal
      abscesses, and anastomotic leaks and stenosis were recorded. Four types of
      assessment were performed: bursting pressure, hydroxyproline (OHP) content,
      histopathology, and biochemical analysis. RESULTS: Compared to the control group,
      the RSV-treated rats displayed a higher bursting pressure (p < .001) and
      anastomotic OHP content (p < .05)]. RSV treatment leads to significant increase
      in PON activity at both time points and decrease in malondialdehyde levels on
      postoperative day 3 (p < .001). Histopathological analysis revealed that RSV
      administration leads to a better anastomotic healing in terms of mucosal
      ischemia, neovascularization, reepithelialization, fibroblast, and lymphocyte
      infiltration. CONCLUSION: The study results suggest that exogenous RSV
      administration exerts a positive effect on experimental colonic wound healing in
      the rat. Although the precise cellular mechanisms by which RSV enhances
      anastomotic wound healing is not clear, stimulation of neovascularization,
      generation of collagen synthesis, inhibition of over inflammation, and
      restriction of oxidative injury seems to be of paramount importance.

PMID- 19842891
TI  - Microscopic and ultrastructural changes of the intestine in abdominal compartment
      syndrome.
AB  - BACKGROUND: The purpose of the study was to examine the microscopic changes of
      intestine villus and ultrastructural changes of tight junction in the presence of
      intra-abdominal hypertension (IAH) of 20 mmHg. MATERIALS AND METHODS: Forty
      Sprague-Daley rats (250 +/- 25 g) divided into four groups (n = 10) were studied.
      In 30 animals, the intra-abdominal pressure was increased to 20 mmHg for 1 hr, 2
      hr, and 4 hr, respectively. The others served as controls. The specimens of the
      intestines were submitted to histopathology using hematoxylin and eosin staining,
      and to ultrastructural analysis using a scanning electron microscope. RESULTS:
      The histopathological study revealed different degrees of changes ranging from
      swelling and degeneration of villous epithelial cells to extensive denudation and
      collapse of the villus. Ultrastructural analysis revealed dilatation of the tight
      junctions and paracellular spaces in the presence of IAH. The severity of the
      damage was related to the time of IAH. CONCLUSIONS: Increased IAH caused a
      significant damage to the intestinal epithelium and a marked dilatation of
      intestinal tight junction, leading to the increased mucosal barrier permeability.
      It may explain why IAH was often associated with bacterial translocation and
      sepsis.

PMID- 19842892
TI  - The relationship between pre- and postoperative range of motion utilizing three
      cruciate-retaining total knee prostheses.
AB  - We prospectively examined the relationship between pre- and postoperative range
      of motion utilizing three cruciate retaining knees with various mechanical
      flexion potentials, i.e., two at about 130 degrees -135 degrees (one with
      posterior lip and the other without) and the third at about 140 degrees -145
      degrees . All groups demonstrated mean flexion and range of motion of 116 degrees
      -122 degrees at one year. Combining data from the three cohorts, patients with
      the following preoperative flexion values achieved the indicated mean changes
      (increases) in flexion at one year: < 90 degrees flexion (Delta 23.6 degrees ),
      91 degrees -105 degrees flexion (Delta 19.3 degrees ), and > 105 degrees flexion
      (Delta 1.8 degrees )). Postoperative improvement was inversely related to
      preoperative flexion. The high flex knee yielded the best improvement in range of
      motion (9.7 degrees increase) in the highest flex preoperative group compared to
      that of the other knees (-7.4 degrees to 2.9 degrees ). Hence, a high flex knee
      design seems to be important in high preoperative range of motion patients
      obtaining an increase in the postoperative range of motion rather than possible
      regression.

PMID- 19842893
TI  - Influence of hydroxyethyl starch on healing of colonic anastomosis in a rat model
      of peritonitis.
AB  - BACKGROUND: This study was designed to evaluate the role of different
      intravascular volume replacement regimens of HES 130/0.4 on wound healing process
      in left colonic anastomoses in the presence of intra-abdominal sepsis induced by
      murine model of cecal ligation and puncture (CLP). METHODS: The left colonic
      anastomosis was performed in 40 rats that were divided into five groups (n =
      8/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES
      (7.5, 15, or 30 ml/kg, respectively). Saline or HES was treated before the
      construction of left colonic anastomosis and on a regular daily basis.
      Anastomotic bursting pressures were measured in vivo on day 5. Tissue samples
      were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO)
      activity, malondialdehyde (MDA), reduced glutathione (GSH) levels, and nuclear
      factor-kappa B (NF-kappa B) activation. The plasma levels of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-6 were also measured. RESULTS: Intra
      abdominal sepsis led to significant decreases in colonic anastomotic bursting
      pressures, and perianastomotic tissue HP contents and GSH levels, along with
      increases in perianastomotic tissue MPO activity, MDA levels and NF-kappa B
      activation and plasma levels of TNF-alpha and IL-6. After treated with HES, these
      provoked perianastomotic tissue MPO activity, MDA levels, NF-kappa B activation,
      and plasma levels of TNF-alpha and IL-6 were suppressed and GSH levels were
      restored, especially in 15 ml/kg HES group. Without obvious influence on systemic
      nutritional condition, HES 15 ml/kg but not HES 7.5 ml/kg significantly increased
      anastomotic bursting pressures, and perianastomotic tissue HP contents. However,
      HES 30 ml/kg even led to adverse effects on anastomotic bursting pressures.
      CONCLUSIONS: This study showed that moderate doses (15 ml/kg) of HES 130/0.4
      administration significantly prevented this intraperitoneal sepsis-induced
      impaired anastomotic healing of the left colon. It also suggested the possibility
      of poorer anastomotic healing receiving HES at higher doses (30 ml/kg). Clearly,
      HES 130/0.4 now should not be recommended to use at a high doses postoperatively
      in sepsis.

PMID- 19842894
TI  - Improvement of the tissue-adhesive and sealing effect of fibrin sealant using
      polyglycolic acid felt.
AB  - Although fibrin sealant (FS) has an advantage of high biocompatibility, its
      adhesive force and sealing effect have been generally considered to be
      inadequate. In the present study, a high adhesive force and sealing effect were
      obtained by first rubbing fibrinogen solution into the target tissue, attaching
      polyglycolic acid (PGA) felt to the treated area, and finally spraying it with
      FS. This method was compared with three conventional FS application methods and a
      method using fibrin glue-coated collagen fleece. The adhesive force resulting
      from the present method was 12 times higher than that for the sequential
      application method, 4.5 times higher than the spray method, 2.5 times higher than
      the rubbing and spray method, and 2.2 times higher than the use of fibrin glue
      coated collagen fleece. The high adhesive force of FS with PGA felt seemed to be
      due the high fibrin content of the fibrin gel (FG). Light and electron
      microscopic observations suggested that the formation of FG in closer contact
      with the muscle fibers was a factor contributing to this superior adhesive force.
      Comparison of the sealing effect of the present method with other methods using
      various biomaterials in combination with FS showed that the sealing effect of FS
      with PGA felt was 1.4 times higher that of polyglactin 910, 1.8 times that of
      polytetrafluoroethylene, and 6.7 times that of oxidized regenerated cellulose.

PMID- 19842896
TI  - Introduction A l'Etude de la Medecine Experimentale--surgical revolution part II.
AB  - The book that Claude Bernard (1813-1878) published in 1865, the Introduction a
      l'Etude de la Medecine Experimentale, fostered a revolution that we believe
      influenced the practice of surgery when the discipline became a scientific
      enterprise. In Part I, we set the stage by presenting the life and
      accomplishments of Bernard, by reviewing his science, and introducing his
      experimental medicine work. In this issue in Part II, we further analyze his book
      and determine the "why" of a genuine surgical revolution. What were the factors
      that generated this revolution, and how a new generation of surgeons learned to
      become better researchers, and thus better surgeons, were the main objectives of
      this work. Science, research, and surgery became highly intertwined and the
      surgeon pursued these fields of knowledge more effectively.

PMID- 19842897
TI  - Michael E. DeBakey: reformer of cardiovascular surgery.
AB  - In cardiac medicine, Dr. Michael Ellis DeBakey is the undisputed pioneer of this
      century, maybe even in history. The design of the ventricular assist device
      (VAD), the Dacron-created artificial blood vessel and his many other firsts
      revolutionized heart surgery (specifically aortic surgery) forever. In fact, his
      contributions were enormous and left and amazing legacy. DeBakey was known to
      have a temper and that he was a very difficult surgeon to work with. However,
      even his critics could not deny the impact he had on the world of medicine. In
      his early nineties, he still practiced surgery. DeBakey was a man that
      accomplished all he set out to do and died on early July 2008.

PMID- 19842898
TI  - The effects of cyclooxygenase (COX)-2 inhibition on ischemia-reperfusion injury
      in liver transplantation.
AB  - PURPOSE: Our objective was to evaluate whether COX-2 inhibition with FK3311, a
      selective cyclooxygenase (COX)-2 inhibitor, improves transplanted liver function.
      METHODS: Inbred male Lewis rats weighing 200-260 g were used. The donor liver was
      perfused with cold University of Wisconsin (UW) solution and then stored in the
      same solution at 4 degrees C for 18 hr. After the preservation period, orthotopic
      liver transplantation was performed. Animals were divided into three groups: the
      control group; the FK low-dose group (1 mg/kg FK3311 i.v. 20 min before
      reperfusion); and the FK high-dose group (3 mg/kg FK3311 i.v. 20 min before
      reperfusion). Survival rate, serum GOT and GPT levels, liver tissue blood flow,
      and serum thromboxane B(2) (TxB(2)) levels were compared among groups. RESULTS:
      Survival rate was significantly better (p <. 05) and serum GOT levels 30 min
      after reperfusion were significantly lower (p <. 05) in the FK high-dose group
      compared to the other two groups. Four hours after reperfusion, GPT levels and
      liver tissue flow were significantly (p <. 05) better in the FK high-dose group
      compared to the control. Both 30 min and 4 hr after reperfusion, serum TxB(2)
      levels were significantly lower in the FK high-dose group compared to the control
      (p <. 05). CONCLUSION: COX-2 activity results in deteriorated liver function
      after I/R injury associated with transplantation, and selective COX-2 inhibition
      improved liver graft function.

PMID- 19842899
TI  - Effects of a serotonin S2-receptor blocker on healing of acute and chronic tendon
      injuries.
AB  - The beneficial effects of serotonin S(2)-receptor blockers on healing skin and
      muscle ulcers and refractory lesions such as leprosy and diabetic and ischemic
      ulcers have been reported previously, but their mechanisms of actions are not
      clear. The present study sought to elucidate the action of an S(2)-receptor
      blocker, metrenperone, on the healing of collagenase-induced injuries in
      superficial digital flexor tendons of two groups of rabbits. In one group, oral
      and topical therapy for 28 days with metrenperone, was started within 48 hr of a
      single acute injury. The animals were then left untreated for another 60 days,
      when it was found that most of the morphological, biochemical, and biomechanical
      characteristics of the healed tendons matched those of their normal uninjured
      controls. Injured, untreated controls showed poor healing. In the second group of
      animals, tendon injury was induced by four separate injections of collagenase at
      weekly intervals. The rabbits were left for another 60 days, before being treated
      with metrenperone for 26 days. This delayed treatment had no apparent effect on
      the biomechanical, biochemical, or morphological characteristics of the healing
      tendons. It appeared that metrenperone had a significant effect on collagen
      turnover and organization of scar tissue, but only while the inflammatory and
      fibroplastic processes were active in the early stages of healing. S(2)-receptor
      blockers may, therefore, be of potential value for modulating repair in acutely
      injured collagenous tissue.

PMID- 19842900
TI  - Impact of proinflammatory cytokine knockout on mesh integration.
AB  - Placement of mesh is involved in 75-80% of hernia operations. It is known that an
      exaggerated foreign body reaction leads to clinical complications. To further
      improve patients outcome using biotechnological agents targeted against tumor
      necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6), a study was conducted
      investigating the impact of cytokine knockout on mesh integration. Sixty mice
      were used: C57BL/6 wild type control, C57BL/6-IL-6 interleukin-6 knockout,
      C57BL/6-Tnfrsf1a knockout of TNF-alpha receptor 1, and C57BL/6-Tnfrsf1b knockout
      of TNF-alpha receptor 2. Standard polypropylene mesh was implanted subcutaneously
      for 7, 21, and 90 days. The inflammatory and connective tissue formation was
      characterized by diameter of inner cellular infiltrate and outer fibrous capsule
      of the foreign body granuloma, and by quantity (collagen/protein ratio) and
      quality (collagen type I/III ratio) of collagen formation. Microscopic
      investigation of the mesh/host-tissue interface showed typical formation of
      foreign body granulomas. Ninety days after implantation none of the knockout
      strains showed significant differences compared to the control group
      investigating amount of inflammatory and connective tissue formation. Analyzing
      the quantity of filamentary collagen deposition the C57BL/6-IL-6 group showed
      significant lowered values compared to the control group 90 days after
      implantation. In all groups collagen type I/III ratio increased over time as an
      indicator for maturation of the surrounding collagen formation. However, no
      difference was found comparing strains at the end of the observation period. The
      results support the notion that wound healing is affected by cytokine deficiency.
      However, a desirable reduced amount of inflammatory tissue formation as well as
      an increased collagen type I/III ratio due to cytokine knockout could not be
      observed.

PMID- 19842901
TI  - Prevention of postoperative peritoneal adhesions by administration of estrogen.
AB  - AIM: Postoperative abdominal adhesions represent one of the most common causes of
      intestinal obstruction in surgical patients. In this study, the effects of
      intraperitoneal administration of estrogen on the development of postoperative
      intraabdominal adhesions and peritoneal leucocytes in a rat adhesion model were
      investigated. METHODS: Sixty Wistar albino rats were divided into three groups.
      Group 1 (control group) had their abdomen closed after surgery without
      administration of any material or drug. Group 2 (saline group) received 2 ml of
      0.9% NaCl, and group 3 (estrogen group) animals received a single intraperitoneal
      dose of 2 cc (1 mg) estrogen (Estradiol propionate, 50.000U, Akrofilline,
      Biofarma, Turkey). All the groups were exposed to the same adhesion-creating
      procedure (Swolin K. Experimental studies on the prevention of intra-abdominal
      adhesions. Studies on rats with an emulsion of lipid and prednisolone. Acta
      Obstet Gynecol Scand. 1966;45:473-498.). After 7-42 days, all animals were
      sacrificed. Adhesions were scored and peritoneal leucocytes were counted.
      RESULTS: The adhesion formation and peritoneal leucocyte count of the estrogen
      group were significantly less than the control and saline groups and a
      statistically significant difference was determined in comparison of those groups
      (p <. 05). CONCLUSION: We concluded that intraperitoneal estrogen decreases the
      incidence of postoperative intraabdominal adhesion formation in rat adhesion
      model.

PMID- 19842902
TI  - Comparison of near-infrared spectroscopy and laser Doppler flowmetry for
      detecting decreased hepatic inflow in the porcine liver.
AB  - Hepatic artery and portal vein thrombosis are devastating complications of
      partial liver transplantation. Early detection of inflow complications is
      important, as re-reconstruction can salvage the graft. Near-infrared spectroscopy
      or laser Doppler flowmetry can be used to detect tissue oxygenation or
      microcirculation on the liver surface. The aim of this study was to examine which
      of these two methods better detects changes in hepatic inflow. Sangen-strain pigs
      (n = 5) were used. The tips of the near-infrared spectroscopy and laser Doppler
      flowmetry probes were placed separately on the surface of the right liver. Inflow
      to the liver was controlled during the following seven conditions: control (not
      clamped), half- and totally clamped portal vein, half- and totally clamped
      hepatic artery, and half- and totally clamped portal vein and artery. Tissue
      blood flow was calculated using laser Doppler flowmetry. Oxyhemoglobin,
      deoxyhemoglobin, and the tissue oxygenation index were measured and calculated
      using a near-infrared spectroscopy system. The tissue blood flow and oxygenation
      index could not be used to differentiate between the half-clamped portal vein,
      half-clamped hepatic artery, and totally clamped portal vein conditions. The
      oxyhemoglobin minus deoxyhemoglobin value was significantly decreased after half
      or total clamping of the portal vein or hepatic artery (p <. 001 for each
      condition). The findings of the present study indicate that near-infrared
      spectroscopy was more sensitive than Doppler flowmetry for detecting changes in
      hepatic tissue inflow from the liver surface.

PMID- 19842904
TI  - The pig as an experimental model for colonic healing study of leakage and
      ischemia in colonic anastomosis.
AB  - BACKGROUND: The object of this experimental study was to develop a model of
      anastomotic failure due to primary leakage and ischemia in porcine large bowel
      anastomosis. METHODS: End-to-end anastomosis was constructed at descending colon
      in 12 pigs. The pigs were randomly divided into three groups. In Group A, the
      anastomosis was applied with a leak of 18 mm. In Group B, in addition to primary
      leakage, an artificial ischemia of the proximal anastomotic bowel segment was
      created by ligation of supplying vessels over 5 cm. In Group C, an artificial
      ischemia was created in the same manner at the proximal and distal anastomotic
      segment and the anastomosis was applied with an intentional leakage as in Groups
      A and B. The animals were sacrificed immediately in case of clinical signs of
      anastomotic dehiscence, sepsis, peritonitis, or ileus. The animals were
      sacrificed on day 28. The peritoneal cavity was examined for peritonitis,
      anastomotic wound dehiscence, and pericolic abscess formation. RESULTS: Distinct
      fibrinous coverings and adhesions at the anastomotic area were found in all
      animals. In cases of primary leakage without ischemia, only one of the four
      animals developed abscess at anastomotic side with clinical sepsis. In cases of
      primary leakage with ischemia of the proximal anastomotic bowel segment, one of
      the four animals presented generalized peritonitis with sepsis. In Group C, there
      were no signs of leakage or peritonitis, although three of the four animals
      developed colonic ileus due to obturation of the colonic lumen by a clot of
      necrotic bowel wall. CONCLUSION: Large anastomotic dehiscence and local ischemia
      of the bowel wall are not reliable factors for the development of intra-abdominal
      abscess, peritonitis, or sepsis in the pig model.

PMID- 19842903
TI  - A new approach for decreasing postoperative peritoneal adhesions: preventing
      peritoneal trauma with soybean oil.
AB  - BACKGROUND: Covering peritoneal surfaces with soybean oil may decrease peritoneal
      adhesions by preventing peritoneal trauma. METHOD(S): Forty female albino Wistar
      rats were divided into four equal groups. In Group 1, soybean oil only (0.1 ml)
      was injected into the peritoneal cavity. In Group 2, an untreated adhesion model
      was generated. In Group 3, an adhesion model was generated, followed by covering
      the area with soybean oil (0.1 ml). In Group 4, the area was first covered with
      soybean oil (0.1 ml) followed by generation of an adhesion model. All rats were
      sacrificed on postoperative day 10, and adhesions were scored. RESULTS: The mean
      macroscopic adhesion scores in Groups 1, 2, 3, and 4 were 0.0 +/- 0.0, 2.90 +/-
      0.21, 1.90 +/- 0.94, and 0.50 +/- 0.71, respectively. The Group 4 score differed
      significantly from that of Group 2 (p <. 001), but was not different from that of
      Group 1 or 3 (p >. 05). DISCUSSION: Soybean oil can effectively decrease adhesion
      formation if applied before peritoneal trauma.

PMID- 19842905
TI  - The plication and splinting procedure for idiopathic sclerosing encapsulating
      peritonitis.
AB  - Idiopathic sclerosing encapsulating peritonitis (ISEP) is a rare cause of small
      intestinal obstruction. Histologically, ISEP is characterized by a thick fibrotic
      membrane encasing the small bowel without any apparent pathophysiological
      factors. While ISEP is predominantly present congenitally in female adolescents
      from subtropical region, it has been identified throughout the world. Evidence
      based effective diagnostics and treatments are pitifully thin. We experienced six
      cases, four males and two females, which exhibited symptoms in their later
      thirties and forties. Five patients presented with acute and subacute intestinal
      obstruction, and one patient with cryptorchidism and seminoma was referred. Due
      to the limitation in distention and motility of bowel loops of ISEP, imaging
      exams may not be very reliable for accurate diagnosis and estimation of
      obstruction progress. They were successfully treated with the mesenteric
      plication and intraluminal splinting procedures. Two cases had an uneventful
      postoperative period, and the returns of normal bowel function were delayed in
      the other four patients. Two recurrences of small bowel obstructions were noted
      over a mean follow-up period of 33 months with mild symptoms. This article
      reviews the patterns of clinical presentations, diagnostic clues, and theories of
      potential risk factors of ISEP as well as its controversial surgical managements.

PMID- 19842906
TI  - Short-term adaptation of rat intestine to ileostomy: implication for pediatric
      practice.
AB  - BACKGROUND: Surgical neonates with complex intestinal conditions, such as
      enterocolitis, midgut volvulus with bowel loss and multiple atresias, often
      require temporary stomas. Little is known on the postsurgical response of the
      altered gut segments, although adaptation is an important consideration in
      neonatal postoperative care, particularly after stoma closure. MATERIALS AND
      METHODS: Rats underwent bowel resection at a point 15 cm proximal to the
      ileocecal valve, and a split ileostomy was performed. On the 6th postoperative
      day the mucosal thickness was calculated with Soft Imaging System Analysis Pro,
      the rate of proliferation was measured following Ki67 immunohistochemistry and
      the apoptotic index was determined on sections stained with ApopTag Plus. The
      intestinal motor activity was recorded on isolated gut segments. Neuronal nitric
      oxide synthase (nNOS) expression and distribution was examined with NADPH
      diaphorase histochemistry and Western blot analysis. RESULTS: An increased wet
      weight of the mucosa and a pronounced mucosal thickening were observed in the
      proximal functional bowel segment. Enterocyte proliferation rate was increased
      significantly, while the apoptotic index remained unchanged in the epithelial
      layer. The dilation of the gut lumen resulted in a morphological change in the
      nitrergic myenteric network with an overexpression of nNOS. As a consequence of
      the surgical procedure, the functional proximal gut segment showed strong and
      frequent contraction waves, with an enhanced responsiveness to cholinergic
      stimuli. CONCLUSIONS: The dilated functional bowel segment was characterized by
      hyperplasic changes in the mucosa and stronger mechanical activity with
      overproduction of nNOS. Although early restoration of intestinal continuity is
      recommended, our observations on adaptive changes may partly explain intestinal
      motility disorders after early stoma closure, suggesting the need for a careful
      approach to a redo-laparotomy.

PMID- 19842907
TI  - Searching for NF-kappaB-based treatments of ischemia reperfusion injury.
AB  - When a tissue becomes ischemic, a host of changes occur at the cellular level
      that lead to a shift in transcriptional activity of many inflammatory and
      cytoprotective compounds, a process which is extensively controlled through a
      family of transcription factors known as nuclear factor kappa-B (NF-kappaB). This
      shift in activity paradoxically results in both a cytoprotective effect at the
      cellular level and upon reperfusion, a generally destructive inflammatory
      response, a phenomenon referred to as ischemia reperfusion (IR) injury. To date,
      a number of methods of modifying the activity of NF-kappaB through either
      physiologic or pharmacologic manipulation have been developed and studied in
      animal models of IR injury and in some cases in human clinical trials. Nearly
      every method of NF-kappaB antagonism has demonstrated a discrete protective
      effect allowing investigators to reduce myocardial infarct sizes by 60% and
      cerebral infarct sizes by 57% relative to untreated control animals. The problem
      of IR injury is all too common and represents a discrete threat not only to the
      tissues directly involved in the ischemic event, but also to distal sites as well
      as is seen in the evolution of acute respiratory distress and severe inflammatory
      response syndromes. In the course of this review, the nature of NF-kappaB and its
      involvement in IR injury is examined along with the efficacy of the various NF
      kappaB-based investigational treatment developed to date.

PMID- 19842908
TI  - Principles of anesthesia monitoring and electrocardiogram.

PMID- 19842910
TI  - Effect of sample preparation method on quantification of polymorphs using PXRD.
AB  - The purpose of this study was to improve the sensitivity and accuracy of
      quantitative analysis of polymorphic mixtures. Various techniques such as hand
      grinding and mixing (in mortar and pestle), air jet milling and ball milling for
      micronization of particle and mixing were used to prepare binary mixtures. Using
      these techniques, mixtures of form I and form II of clopidogrel bisulphate were
      prepared in various proportions from 0-5% w/w of form I in form II and subjected
      to x-ray powder diffraction analysis. In order to obtain good resolution in
      minimum time, step time and step size were varied to optimize scan rate. Among
      the six combinations, step size of 0.05 degrees with step time of 5 s
      demonstrated identification of maximum characteristic peaks of form I in form II.
      Data obtained from samples prepared using both grinding and mixing in ball mill
      showed good analytical sensitivity and accuracy compared to other methods. Powder
      x-ray diffraction method was reproducible, precise with LOD of 0.29% and LOQ of
      0.91%. Validation results showed excellent correlation between actual and
      predicted concentration with R2 > 0.9999.

PMID- 19842911
TI  - The effects of excipients for topical preparations on the human skin permeability
      of terpinen-4-ol contained in Tea tree oil: infrared spectroscopic
      investigations.
AB  - This work aimed to evaluate the effect induced by excipients conventionally used
      for topical dosage forms, namely isopropyl myristate (IPM) or oleic acid (OA) or
      polyethylene glycol 400 (PEG400) or Transcutol (TR), on the human skin
      permeability of terpinen-4-ol (T4OL) contained in the pure Tea tree oil. The
      effect of such excipients was determined by evaluating the absorption of T4OL
      using human epidermis and the perturbation of the organization of stratum corneum
      by ATR-FTIR. Among the tested excipients OA enhanced the absorption of T4OL by
      perturbing the stratum corneum lipid barrier. Other excipients caused a weak
      enhancement effect and their use should be carefully monitored.

PMID- 19842912
TI  - Protective effects of cysteine analogues on acute myocardial ischemia: novel
      modulators of endogenous H(2)S production.
AB  - The current study was designed to evaluate the pharmacologic effects of three
      novel cysteine-containing compounds: S-propyl-l-cysteine (SPC), S-allyl-l
      cysteine (SAC), and S-propargyl-l-cysteine (SPRC) on H(2)S production and
      antioxidant defenses in an acute myocardial infarction (MI) rat model. The
      enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and
      glutathione peroxidase (GPx), as well as glutathione redox status and
      malonaldehyde (MDA) content, also were determined. All three compounds were found
      to preserve SOD and GPx activities and also tissue GSH levels while reducing the
      formation of the lipid peroxidation product MDA in ventricular tissues. With
      immunfluorescence assays, we observed the expression of CSE and Mn-SOD. The
      morphologic changes of the cardiac cells are seen with both light and electron
      microscopy. The corresponding pathologic alterations were characterized mainly as
      loss of adherence between cardiac myocytes and swollen or ruptured mitochondria
      at the ultrastructural level. Propargylglycine, a selective inhibitor of CSE,
      abolished the protective effects of each compound used in the current model. Our
      study provides novel evidence that SPC, SAC, and SPRC have cardioprotective
      effects in MI by reducing the deleterious effects of oxidative stress by
      modulating the endogenous levels of H(2)S and preserving the activities of
      antioxidant defensive enzymes like SOD.

PMID- 19842913
TI  - The hydrogen sulfide donor NaHS promotes angiogenesis in a rat model of hind limb
      ischemia.
AB  - It is not known whether H(2)S can promote angiogenesis with improvement of
      regional blood flow in ischemic organs. Sodium hydrosulfide (NaHS, a H(2)S donor)
      was administered once a day for 4 w following femoral artery ligation. Collateral
      vessel growth, capillary density, regional tissue blood flow, the expression of
      endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and Akt were examined
      during or at the end of the treatment period. NaHS treatment significantly
      increased collateral vessel growth, capillary density, and regional tissue blood
      flow in ischemic hind limb muscles compared with the controls. These effects were
      associated with an increase in VEGF expression in the skeletal muscles and VEGFR2
      phosphorylation in the neighboring vascular endothelial cells, suggesting a role
      of VEGF in mediating the NaHS effects in a cell-cell interaction pattern.
      Moreover, NaHS treatment also resulted in an increase in Akt phosphorylation in
      ischemic hind limb muscles. In conclusion, our observations with NaHS strongly
      suggest that H(2)S is a proangiogenic factor in chronic ischemia. The
      proangiogenic effect of NaHS may be mediated by interaction between the
      upregulated VEGF in the skeletal muscle cells and the VEGFR2 as well as its
      downstream signaling element Akt in the vascular endothelial cells.

PMID- 19842914
TI  - Enhancement of long-term proliferative capacity of rabbit corneal epithelial
      cells by embryonic stem cell conditioned medium.
AB  - Induction of autologous stem cells for directed differentiation has become a
      predominant method to obtain autologous cells for tissue reconstruction. However,
      the low inducing efficiency and contamination with other type of cells hinder its
      clinical utilization. Here we report a novel phenomenon that the corneal
      epithelial cells maintain long-term proliferative capacity and tissue-specific
      cell phenotype by factors secreted from murine embryonic stem cells (ESCs). The
      rabbit corneal epithelial cells grew very well in culture medium with addition of
      40% ESC conditioned medium (ESC-CM). These corneal epithelial cells have been
      serially subcultured for more than 20 passages and maintained high cell purity,
      cobble-stone-like morphology, enhanced colony forming efficiency, normal diploid,
      and capacity to regenerate a functional stratified corneal epithelial equivalent.
      More importantly, these cells did not form tumor, and the cells lost their
      proliferative capacity after withdrawal of ESC-CM. The long-term proliferative
      capacity of corneal epithelial cells is partly resulted from enhancement of cell
      survival and colony formation, and mediated by ectopic expression of telomerase.
      Our findings indicate that this new ESC-CM culture system can generate low
      immunogenic autologous cells sufficiently for use in regenerative medicine.

PMID- 19842916
TI  - Random mitotic activities across human embryonic stem cell colonies.
AB  - A systemic and quantitative study was performed to examine whether different
      levels of mitotic activities, assessed by the percentage of S-phase cells at any
      given time point, existed at different physical regions of human embryonic stem
      (hES) cell colonies at 2, 4, 6 days after cell passaging. Mitotically active
      cells were identified by the positive incorporation of 5-bromo-2-deoxyuridine
      (BrdU) within their newly synthesized DNA. Our data indicated that mitotically
      active cells were often distributed as clusters randomly across the colonies
      within the examined growth period, presumably resulting from local deposition of
      newly divided cells. This latter notion was further demonstrated by the confined
      growth of enhanced green florescence protein (EGFP) expressing cells amongst non
      GFP expressing cells. Furthermore, the overall percentage of mitotically active
      cells remained constantly at about 50% throughout the 6-day culture period,
      indicating mitotic activities of hES cell cultures were time-independent under
      current growth conditions.

PMID- 19842915
TI  - Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic
      potential in human adult bone-marrow-derived mesenchymal stem cells.
AB  - We compared human mesenchymal stem cells (hMSCs), expanded long term with and
      without fibroblast growth factor (FGF) supplementation, with respect to
      proliferation, and the ability to undergo chondrogenesis in vitro. hMSCs expanded
      in FGF-supplemented medium proliferated more rapidly than the control cells.
      Aggregates of FGF-treated cells exhibited chondrogenic differentiation at all
      passages tested although, in some preparations, differentiation was diminished
      after seventh passage. Aggregates made with control cells differentiated along
      the chondrogenic lineage after first passage but exhibited only marginal
      differentiation after fourth and failed to form cartilage after seventh passage.
      Microarray analysis of gene expression identified 334 transcripts differentially
      expressed in fourth passage control cells that had reduced chondrogenic
      potential, compared with the fourth passage FGF-treated cells that retained this
      capacity, and 243 transcripts that were differentially expressed when comparing
      them to the first passage control cells that were also capable of differentiating
      into chondrocytes. The intersection of these analyses yielded 49 transcripts
      differentially expressed in cells that exhibited chondrogenic differentiation in
      vitro compared with the cells that did not. Among these, angiopoietin 1, secreted
      frizzled-related protein 1, and six transmembrane epithelial antigen of the
      prostate 1 appear to be of higher relevance. These preliminary data must now be
      validated to verify whether different gene expression profiles translate into
      functional differences. In summary, these findings suggest that the chondrogenic
      potential of hMSCs is vulnerable to cell expansion and that care should be
      exercised when expanding these cells for cartilage tissue engineering
      applications. Supplementation with FGF-2 allows reaching target cell numbers more
      rapidly and extends the level of expansion within which these cells are useful
      for tissue-engineered cartilage repair.

PMID- 19842918
TI  - Henry James and the art of the dream.

PMID- 19842917
TI  - Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery
      system for clindamycin phosphate.
AB  - To develop more effective treatment for bacterial vaginosis, bioadhesive film
      formulations of clindamycin phosphate (CL) for vaginal delivery were studied. The
      bioadhesive films were prepared by solvent evaporation method. A 3(2) full
      factorial design was utilized for optimization of the effect of independent
      variables such as amount of hydroxypropyl cellulose (X1), amount of xanthan gum
      (X2) on mechanical properties, and % drug retained on vaginal mucosa. The films
      were evaluated for various aesthetic and physicodynamic properties. Batch F(86)
      showed highest overall desirability of 0.99. Batch F86 was considered optimal
      composition for a novel bioadhesive vaginal formulation, as they have good
      peelability, high % elongation at break, moderate tensile strength, and retained
      on vaginal mucosa up to 8 h. Also, films were non-cytotoxic as indicated by
      negligible decrease in cell viability. Our study may provide a potential vaginal
      delivery system of CL against bacterial vaginosis.

PMID- 19842919
TI  - A psychoanalytic look at Herman Melville from his use of source materials for
      Moby-Dick.

PMID- 19842920
TI  - The piano teacher: a case study in perversion and sadomasochism.

PMID- 19842921
TI  - "Psychoanalysis and the unconscious" and D.W. Winnicott's transitional and
      related phenomena.

PMID- 19842922
TI  - Magritte, the work of art, and Lacan's three dimensions of experience: from
      idealization to sublimation, from resemblance to similitude, and from the id to
      it.

PMID- 19842923
TI  - Torture and attachment: conscience and the analyst's world-seeing eye.

PMID- 19842926
TI  - Pharmacogenomics and medication overuse headache: when the cure may turn to
      poison.

PMID- 19842929
TI  - Institutional Profile: The University of California Pharmacogenomics Center: at
      the interface of genomics, biological mechanisms and drug therapy.
AB  - The Pharmacogenomics Center of the University of California, San Francisco (CA,
      USA) fosters research and educational activities focused on the genomic basis for
      variation in drug response. Investigators in the Center conduct multidisciplinary
      and multicenter research on a diverse array of clinically used drugs with the
      goal of understanding the genetic factors that contribute to variation in
      therapeutic and adverse drug response. The Center houses the large NIH-supported
      Pharmacogenomics of Membrane Transporters Project, which is a leader in
      understanding genetic variation in membrane transporters that are important in
      clinical drug response. Center investigators study racially and ethnically
      diverse populations, are pioneers in the education of PharmD, MD and PhD students
      in pharmacogenomics, and have led the establishment of unique graduate and
      postdoctoral training programs focused on pharmacogenomics. A key emphasis of the
      Center is on biological mechanisms with a goal of facilitating the development of
      safer and more effective medications.

PMID- 19842930
TI  - Pyrosequencing-based screening for the genetic polymorphism CYP2B6 1459 C > T.

PMID- 19842931
TI  - GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)
      adrenergic blockade in humans.
AB  - AIMS: A common, functionally significant polymorphism in GRK5 (Gln41Leu) encodes
      a gain-of-function enzyme that enhances desensitization of the beta(1)-adrenergic
      receptor. GRK5 Leu41 has been postulated to confer endogenous 'genetic beta
      blockade' and contribute to an attenuated response to beta-blockers in black
      subjects. The effects of this GRK5 variant on sensitivity to a beta-blocker have
      not been studied in humans. We hypothesized that the GRK5 Gln41Leu variant
      contributes to interindividual variability in response to beta-blockade and to
      the ethnic difference in sensitivity between black and Caucasian individuals.
      MATERIALS & METHODS: We measured the heart rate at rest and during a graded
      incremental exercise in 154 healthy subjects (85 white and 69 black) before and
      after an oral administration of 25 mg atenolol. We determined the genotypes of
      GRK5 (Gln41Leu), beta(1)-adrenergic receptor (ADRB1 Ser49Gly and Arg389Gly)
      genotypes and plasma atenolol concentrations. The effects of genotype and
      covariates on sensitivity to atenolol, measured as the reduction in exercise
      induced tachycardia, were determined using multiple regression analyses. RESULTS:
      The minor allele frequency of GRK5 Leu41 was 32.6% in blacks and 0% in whites.
      Black individuals were less sensitive to atenolol than white individuals (p < or
      = 0.011) but this was not explained by the GRK5 genotype. The GRK5 genotype had
      no effect on resting heart rate before (p = 0.61) and after adjustment for age,
      sex, ethnicity, atenolol concentrations, BMI and ADRB1 genotypes (p = 0.81). The
      decrease in heart rate after atenolol administration did not differ significantly
      according to the GRK5 genotype at rest or after exercise, before (all p > 0.14)
      and after statistical adjustment for covariates (all p > 0.17). CONCLUSION: The
      GRK5 Gln41Leu polymorphism does not affect sensitivity to the beta(1)-adrenergic
      blocker, atenolol, during acute physiological adrenergic stimulation, nor does it
      contribute to the ethnic differences in sensitivity to atenolol among black and
      Caucasian individuals.

PMID- 19842932
TI  - Association between ABCC2 polymorphism and lopinavir accumulation in peripheral
      blood mononuclear cells of HIV-infected patients.
AB  - AIM: Lopinavir (LPV) is a potent protease inhibitor used in combination with low
      doses of ritonavir in the treatment of HIV-infected patients. LPV
      pharmacokinetics is characterized by a large interindividual variability
      requiring the use of therapeutic drug monitoring in different clinical
      situations. While the sources of this variability are still unknown, several
      genetic polymorphisms in biotransformation enzymes or transporter proteins
      involved in the metabolism and/or the distribution of LPV appear as good
      candidates. Therefore, the aim of the present study was to investigate the
      influence of selected genetic polymorphisms on LPV trough plasma concentrations
      ([LPV](Cmin)), LPV concentrations in peripheral blood mononuclear cells
      ([LPV](CC)) and the LPV accumulation ratio ([LPV](CC):[LPV](Cmin)). MATERIALS &
      METHODS: A total of 53 patients receiving Kaletra((R)) (Abbott Laboratories, IL,
      USA) (LPV+ritonavir) were genotyped for 14 different polymorphisms in
      biotransformation enzymes and transporter proteins. [LPV](Cmin), [LPV](CC) and
      [LPV](CC):[LPV](Cmin) were compared according to the patient's genotypes. RESULTS
      & CONCLUSION: The 4544G>A (rs8187710)polymorphism in ABCC2 was associated with a
      higher accumulation of LPV in peripheral blood mononuclear cells of HIV-treated
      patients. As already observed in previous studies, ABCB1 or CYP3A5 polymorphisms
      had no impact on [LPV](Cmin) and we did not detect any influence of these
      polymorphisms on [LPV](CC) and its accumulation in mononuclear cells. In
      conclusion, this pilot study suggests, for the first time, that the 4544G>A
      polymorphism in ABCC2 could explain a significant part of the interindividual
      variability in LPV pharmacokinetics. Further investigations are needed to confirm
      this association and to explore its real pharmacodynamic impact.

PMID- 19842933
TI  - Association of the exon 3 deleted/full-length GHR polymorphism with recombinant
      growth hormone dose in growth hormone-deficient adults.
AB  - AIMS: Contradictory reports exist regarding the influence of the exon 3 deleted
      (d3)/full-length (fl) growth hormone receptor (GHR) polymorphism on
      responsiveness to recombinant human growth-hormone therapy in idiopathic short
      stature, small for gestational age and GH-deficient children, Turner syndrome
      patients and GH-deficient adults. In some of these studies, the d3 allele was
      associated with increased responsiveness to GH. The aim of this study was to test
      this association in a group of GH-deficient adult patients receiving recombinant
      GH treatment. MATERIALS & METHODS: Patients were derived from the prospective
      German Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. The
      GHRd3/fl polymorphism was determined in 133 German adult patients (66 men and 67
      women; mean age: 45.4 years +/- 13.1 standard deviation; majority Caucasian) with
      a GH-deficiency of different origin. Patients received GH treatment for 12 months
      with a finished dose-titration of GH and standardized insulin-like growth factor
      (IGF)-1 measurements in one central laboratory. GH dose after 1 year of
      treatment, IGF-1 serum concentrations, IGF-1 standard deviation score (SDS)
      values and anthropometric data were analyzed by GHRd3/fl genotypes. RESULTS:
      After 1 year of GH treatment, the individually required GH dose was significantly
      lower in GH-deficient patients carrying one or two d3 alleles, compared with
      patients with the full-length receptor (p = 0.04). Genotype groups (d3-allele
      carriers vs noncarriers) showed no significant differences in IGF-1 serum
      concentrations (p = 0.51), IGF-1 SDS (p = 0.36) nor in gender (p = 0.53), age (p
      = 0.28), weight (p = 0.13), height (p = 0.53) or BMI (p = 0.15). CONCLUSION: The
      d3-allele carriers required approximately 25% less exogenous GH compared with the
      homozygous fl-allele carriers, which may express an increased responsiveness to
      exogenous GH. Variability of the individually required GH dose in adult GH
      deficient patients may therefore be partly due to the GHRd3/fl polymorphism.
      Further studies are required to confirm these results.

PMID- 19842934
TI  - VKORC1 haplotypes in five East-Asian populations and Indians.
AB  - AIMS: Warfarin, a widely prescribed oral anticoagulant, is used for the
      prevention of thromboembolism. Several polymorphisms in VKORC1 have been shown to
      be associated with warfarin dose requirements. The frequencies of these VKORC1
      polymorphisms display population differences; however, this has not been examined
      in many populations. In this study, we examined VKORC1 polymorphisms in five East
      Asian populations (Han Chinese, Indonesian, Filipino, Thai and Vietnamese) and
      Indians. MATERIALS & METHODS: A total of six SNPs in the VKORC1 gene (-1639G>A,
      497T>G, 1173C>T, 1542T>G, 2255C>T and 3730G>A) were genotyped. Frequencies,
      linkage disequilibrium and haplotype structures of these six VKORC1 SNPs were
      analyzed. RESULTS: Our data showed that 497T>G is only polymorphic in the Indian
      population. The 497G allele is very rare in the East-Asian populations (frequency
      < 1%). The remaining SNPs demonstrated high linkage disequilibrium and had
      similar frequencies and haplotype structures in all but the Indian population.
      The Indian population is mostly made up of the H7 haplotype (76%) while the rest
      of the recruited populations consisted of the H1 haplotype (> 80%).

PMID- 19842935
TI  - Different effects of the ABCG2 c.421C>A SNP on the pharmacokinetics of
      fluvastatin, pravastatin and simvastatin.
AB  - AIMS: This study aimed to investigate possible effects of the ABCG2 c.421C>A
      (p.Gln141Lys; rs2231142) genotype on fluvastatin, pravastatin and simvastatin
      pharmacokinetics. MATERIALS & METHODS: In a crossover study, five healthy
      volunteers with the ABCG2 c.421A/A genotype, four with the c.421C/A genotype and
      23 with the c.421C/C genotype ingested a single 40-mg dose of fluvastatin,
      pravastatin and simvastatin, with a washout period of 1 week. Plasma statin
      concentrations were measured up to 12 h. RESULTS: The estimated marginal mean
      area under the plasma concentration-time curve from 0 h to infinity (AUC(0
      infinity)) of fluvastatin was 97% (p = 0.015) or 72% (p = 0.009) larger in
      participants with the A/A genotype than in those with the C/A or C/C genotype.
      The AUC(0-infinity) of simvastatin lactone was 111% (p = 0.005) larger in
      participants with the A/A genotype than in participants with the C/C genotype.
      The simvastatin acid:lactone AUC(0-infinity) ratio was 46% (p = 0.017) smaller in
      individuals with the A/A genotype than in those with the C/C genotype. The ABCG2
      genotype had no significant effect on simvastatin acid or pravastatin
      pharmacokinetics. CONCLUSIONS: Genetic variability in ABCG2 markedly affects the
      pharmacokinetics of fluvastatin and simvastatin lactone, but has no significant
      effect on pravastatin or active simvastatin acid. Genotyping for ABCG2 in
      addition to SLCO1B1 and ABCB1 polymorphisms could help in predicting statin
      pharmacokinetics when selecting a statin and its dose for an individual patient.

PMID- 19842936
TI  - Pharmacogenetics and pharmacogenomics of sexual dysfunction: current status, gaps
      and potential applications.
AB  - Although treatment of different types of sexual dysfunction has improved in the
      past decade with the introduction of phosphodiesterase type 5 inhibitors and
      selective serotonin reuptake inhibitors, response rates to these targeted
      therapies are variable. There are a number of studies in the published literature
      that provide proof-of-concept that genetic variation contributes to the variable
      response. Pharmacogenomics will most likely be one part of our therapeutic
      armamentarium in the future and will provide a stronger scientific basis for
      optimizing drug therapy on the basis of each patient's genetic constitution. This
      article will review English language medical literature on the state-of-the-art
      genetic polymorphisms of drug targets, transporters and signaling molecules as
      well as pharmacogenetic studies of sexual dysfunction and suggested possible
      applications. Collectively, the data demonstrate that pharmacogenomics in the
      field of sexual medicine is still in its infancy. More research will provide
      further intriguing new discoveries in years to come.

PMID- 19842937
TI  - Mitochondrial gene profiling: translational perspectives.
AB  - The last decade has witnessed the development of multiple microarray platforms
      designed to study, in a comprehensive fashion, the expression and sequence of
      both mitochondrial and nuclear genes that encode mitochondrial proteins.
      Mitochondrial dysfunction has been implicated in a number of severe medical
      conditions including cancer, metabolic diseases (i.e., cardiovascular, diabetes
      and obesity) and neurodegenerative disorders and it is responsible for the
      adverse effects of numerous drugs. Profiling of the genetic and genomic status of
      mitochondria with focused microarrays offers the promise of rapidly and robustly
      identifying novel biomarkers for early disease diagnoses and prognoses,
      predicting of drug safety, liability, and selecting and stratifying of patients
      in clinical trials.

PMID- 19842939
TI  - Pharmacogenetics of tenofovir treatment.
AB  - Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used as part of HIV
      therapy. Its favorable profile in terms of high efficacy, low toxicity and once
      daily dosing makes TDF one of the most attractive antiretroviral agents, and
      therefore, it is widely used. However, cases of kidney tubular dysfunction have
      been reported and concern exists regarding the long term use of TDF. Owing to the
      high interindividual variability in the presentation of kidney function
      abnormalities, research has recently focused on host genetic factors predisposing
      to TDF-associated renal dysfunction. Transporter proteins involved in the renal
      elimination of TDF, such as organic anion transporter 1 or multidrug resistant
      protein 2 or 4, seem to be involved importantly and several genetic polymorphisms
      in these proteins have been associated with an increased risk of kidney
      tubulopathy in patients treated with TDF. In this review, all relevant
      pharmacogenetic factors that may play a role in the risk of renal toxicity
      associated with the use of tenofovir are summarized.

PMID- 19842938
TI  - Genetic factors influencing cytarabine therapy.
AB  - The mainstay of acute myeloid leukemia chemotherapy is the nucleoside analog
      cytarabine (ara-C). Numerous studies suggest that the intracellular
      concentrations of the ara-C active metabolite, ara-CTP, vary widely among
      patients and, in turn, are associated with variability in clinical response to
      acute myeloid leukemia treatment. Thus, genetic variation in key genes in the ara
      C metabolic pathway--specifically, deoxycytidine kinase (a rate-limiting
      activating enzyme), 5 nucleotidase, cytidine deaminase and deoxycytidylate
      deaminase (all three are inactivating enzymes), human equilibrative nucleoside
      transporter (ara-C uptake transporter) and ribonucleotide reductase (RRM1 and
      RRM2--enzymes regulating intracellular deoxycytidine triphosphate pools)--form
      the molecular basis of the interpatient variability observed in intracellular ara
      CTP concentrations and response to ara-C. Understanding genetic variants in the
      key candidate genes involved in the metabolic activation of ara-C, as well as the
      pharmacodynamic targets of ara-C, will provide an opportunity to identify
      patients at an increased risk of adverse reactions or decreased likelihood of
      response, based upon their genetic profile, which in future could help in dose
      optimization to reduce drug toxicity without compromising efficacy. The
      pharmacogenetic studies on ara-C would also be equally applicable to other
      nucleoside analogs, such as gemcitabine, decitabine, clofarabine and so on, which
      are metabolized by the same pathway.

PMID- 19842940
TI  - Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of
      anticoagulant therapy (EU-PACT) trial design.
AB  - The narrow therapeutic range and wide interpatient variability in dose
      requirement make anticoagulation response to coumarin derivatives unpredictable.
      As a result, patients require frequent monitoring to avert adverse effects and
      maintain therapeutic efficacy. Polymorphisms in VKORC1 and CYP2C9 jointly account
      for about 40% of the interindividual variability in dose requirements. To date,
      several pharmacogenetic-guided dosing algorithms for coumarin derivatives,
      predominately for warfarin, have been developed. However, the potential benefit
      of these dosing algorithms in terms of their safety and clinical utility has not
      been adequately investigated in randomized settings. The European
      Pharmacogenetics of Anticoagulant Therapy (EU-PACT) trial will assess, in a
      single-blinded and randomized controlled trial with a follow-up period of 3
      months, the safety and clinical utility of genotype-guided dosing in daily
      practice for the three main coumarin derivatives used in Europe. The primary
      outcome measure is the percentage time in the therapeutic range for international
      normalized ratio. This report describes the design and protocol for the trial.

PMID- 19842941
TI  - Identification of candidate genes for rituximab response in rheumatoid arthritis
      patients by microarray expression profiling in blood cells.
AB  - AIMS: Transient CD20+ B-cell depletion with rituximab is an effective treatment
      for rheumatoid arthritis (RA). However, there is a subgroup of patients that do
      not show significant clinical response to rituximab and for these patients, other
      modes of treatment are preferred. Finding biomarkers for drug response in RA has
      immense potential for improving treatment and lowering healthcare costs for
      treating RA patients by facilitating the optimization of their pharmacotherapy.
      In the present study, we report on gene expression profiles of three different
      blood cell types in rituximab responders and nonresponder RA patients identifying
      new candidate genes associated with rituximab response. MATERIALS & METHODS:
      Transcriptional profiles of whole-blood, CD4+ T cells and B cells were analyzed
      from nine female patients (mean age 53 +/- 11 years) with active RA disease
      (DAS28 > 5.1), starting rituximab therapy using Illumina (CA, USA) gene
      expression microarrays. Whole-blood RNA was extracted using the PAXgene system
      (PreAnalytix, Hombrechtikon, Switzerland) whilst the lymphocyte RNA was obtained
      following cell isolation using negative selection. Flow cytometry analysis was
      performed to determine whole blood subpopulations, as well as the lymphocyte
      isolation purity. A whole-genome expression profiling was performed on the RNA
      samples prepared from the three blood cell populations using the Illumina Human 6
      Beadchip array system version 1 (Illumina). From the group of statistically
      significant genes showing differential expression in rituximab responders
      compared with nonresponder RA patients, we selected a group of candidate genes
      that were subsequently validated in the same RNA samples using TaqMan real-time
      PCR assays. RESULTS: Several genes were identified whose level of expression is
      associated significantly with the response to rituximab in all three blood cell
      types evaluated (multiple-test corrected p-value < 0.05). Real-time PCR-validated
      genes include ARG1 (1.6-fold downregulated in responders) and TRAF1 (1.4-fold
      upregulated in responders) genes in whole blood and TLR4 (1.3-fold upregulated in
      responders) in CD4+ T cells. CONCLUSIONS: The present study is the first gene
      expression microarray analysis reporting on biomarkers of the clinical response
      to rituximab in RA in blood cells. Following validation in larger cohorts, the
      identified genes may serve as biomarkers for treatment choice in RA.

PMID- 19842944
TI  - Inactivation of acetylcholinesterase by various fluorophores.
AB  - The inhibition of recombinant mouse acetylcholinesterase (rMAChE) and electric
      eel acetylcholinesterase (EEAChE) by seven, structurally different chromophore
      based (dansyl, pyrene, dabsyl, diethylamino- and methoxycoumarin, Lissamine
      rhodamine B, and Texas Red) propargyl carboxamides or sulfonamides was studied.
      Diethylaminocoumarin, Lissamine, and Texas Red amides inhibited rMAChE with IC50
      values of 1.00 microM, 0.05 microM, and 0.70 microM, respectively. Lissamine and
      Texas Red amides inhibited EEAChE with IC50 values of 3.57 and 10.4 microM,
      respectively. The other chromophore amides did not inhibit either AChE. The
      surprising inhibitory potency of Lissamine was examined in further detail against
      EEAChE and revealed a mixed-type inhibition with Ki = 11.7 microM (competitive)
      and Ki' = 24.9 microM (noncompetitive), suggesting that Lissamine binds to free
      enzyme and enzyme-substrate complex.

PMID- 19842945
TI  - Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a
      retrospective cohort study.
AB  - CONTEXT: Lithium (Li) is a first-line treatment for bipolar disorder but has a
      narrow therapeutic index. Treatment of Li toxicity includes supportive measures
      and hemodialysis in severe cases, but this modality is not always immediately
      available. Sodium polystyrene sulfonate (SPS, Kayexalate), a cation exchanger,
      has been promising in animal models and human reports to reduce absorption and
      enhance elimination of Li. MATERIAL AND METHODS: A retrospective cohort study was
      conducted. All cases of chronic Li intoxication were reviewed in two adult-care
      hospitals from 2000 to 2009. A group comparison and a within-patient comparison
      were performed to compare the effect of SPS on the median Li half-life (T(1/2)).
      For this study, at least three serum Li levels were required for T(1/2)
      calculations. RESULTS: Forty-eight patients met inclusion requirements, 12 of
      whom had taken SPS. Median Li T(1/2) in the treated and control groups was 20.5
      and 43.2 hours, respectively (p = 0.0006). In the 12 treated patients, Li T(1/2)
      during SPS was on average 48.9% shorter than without SPS. Furthermore, in one
      subject in whom urinary Li data were available, Li clearance with SPS was
      superior to Li renal clearance. Prolonged constipation was noted in one patient
      whereas mild hypokalemia was noted in six patients treated with SPS. CONCLUSION:
      This study shows that SPS reduced Li T(1/2) and suggests that SPS is capable of
      promoting Li elimination in chronic intoxications. These results warrant a
      prospective trial looking at the use of SPS in the treatment of Li overdose as an
      adjunct to supportive measures and hemodialysis.

PMID- 19842946
TI  - Reproductive value and the stochastic demography of age-structured populations.
AB  - The dynamics of an age-structured population in a fluctuating environment is
      determined by the stochastic individual contributions from annual survival and
      fecundity to the total reproductive value of the population the next year. All
      parameters required to describe the population dynamics are simple properties of
      the distribution of these individual demographic contributions, which we call
      individual reproductive value. The asymptotic population growth rate in the
      average environment and the demographic and environmental variances are
      respectively the mean individual reproductive value over individuals through time
      and the variance within and between years. Our approach leads to an intuitive
      understanding of demographic and environmental variances in age-structured
      populations and their decomposition into additive age-specific components due to
      survival and reproduction. We show how to apply this approach to estimate the
      demographic and environmental variances and their components. The estimates are
      based on yearly random samples of individual vital rates and require no
      information about the total population size.

PMID- 19842948
TI  - Establishment of the Japan Association for Interprofessional Education and
      perspectives.

PMID- 19842949
TI  - Formulating competency-based outcomes continues to claim much attention.

PMID- 19842950
TI  - The Leicester Model of Interprofessional education: developing, delivering and
      learning from student voices for 10 years.
AB  - There are few sustained interprofessional learning opportunities in practice
      which engage the whole cohort of health and social care students across a region,
      the Leicester Model of Interprofessional Education is such an example. Since 1995
      the Leicester Model has evolved to enable health and social care students to
      learn about the complexities of delivering multi-agency care in a range of health
      and social care settings. The learning environment is situated at the front line
      of service delivery. The education model takes students through a cycle of
      learning and applies a problem-solving, experiential learning approach which
      promotes deep learning. Follow-up data indicates that deep learning is achieved.
      This paper describes the original setting and presents the evaluation outcomes of
      the Leicester Model's "Health in the Community" course, which is delivered in
      city-centre communities, where inequalities in health are greatest. It traces a
      ten-year trajectory of interprofessional student group evaluations which helped
      shape this learning experience. Year-on-year positive student outcomes indicate
      the potential of the model to motivate and prepare future professionals for team
      working. Its sustainability has been achieved through ensuring the integration of
      education research in the development process, engagement of practitioners who
      value the student contributions to team working, placing patients central to the
      learning experience and establishing working partnerships between Higher
      Education Institutions, local health and social care organizations and the
      voluntary sector.

PMID- 19842951
TI  - An interprofessional course in bioethics: training for real-world dilemmas.
AB  - Future health professionals are often educated with other students of their same
      discipline when, in practice, they will be working with professionals from other
      backgrounds to provide care for the patient. Complex issues of ethical concern
      are common to health professionals due to modern technology. This paper describes
      the evolution of an interprofessional bioethics course that had a unique
      combination of students and faculty. Innovative teaching methods were utilized
      and continuously refined based on student evaluations. Students commonly cited
      the interprofessional interactions as the most enjoyable part of the learning
      experience. Establishing a patient-centered focus and an appreciation of the
      contributions of other disciplines, students learned how to apply ethical
      decision-making to real cases. At the conclusion of the course, students reported
      improved attitudes toward interprofessional teamwork. This course format and
      teaching techniques may be applied at other universities looking for linkages to
      encourage consistent interprofessional collaboration across disciplines.

PMID- 19842952
TI  - The impact of an online interprofessional course in disaster management
      competency and attitude towards interprofessional learning.
AB  - A recent national assessment of emergency planning in Canada suggests that health
      care professionals are not properly prepared for disasters. In response to this
      gap, an interprofessional course in disaster management was developed,
      implemented and evaluated in Toronto, Canada from 2007 to 2008. Undergraduate
      students from five educational institutions in nursing, medicine, paramedicine,
      police, media and health administration programs took an eight-week online
      course. The course was highly interactive and included video, a discussion forum,
      an online board game and opportunity to participate in a high fidelity disaster
      simulation with professional staff. Curriculum developers set interprofessional
      competency as a major course outcome and this concept guided every aspect of
      content and activity development. A study was conducted to examine change in
      students' perceptions of disaster management competency and interprofessional
      attitudes after the course was completed. Results indicate that the course helped
      students master basic disaster management content and raised their awareness of,
      and appreciation for, other members of the interdisciplinary team. The
      undergraduate curriculum must support the development of collaborative
      competencies and ensure learners are prepared to work in collaborative practice.

PMID- 19842953
TI  - Multidisciplinary cancer conferences: exploring the attitudes of cancer care
      providers and administrators.
AB  - The multidisciplinary cancer conference (MCC) provides an outlet for contributors
      in cancer care collectively to evaluate diagnosis and treatment options and to
      provide optimal patient care. The prevalence and perceived benefits of MCCs in
      Canada have not previously been described. Between February and March 2007, the
      Cancer Services Integration Survey, including four key statements concerning
      MCCs, was administered to cancer care providers and administrators in Ontario,
      Canada. A total of 1,769 responses were received with a response rate of 33%.
      Overall, 74% of respondents were aware of MCCs within their region, but only 58%
      were either regular MCC participants, or acknowledged participation of cancer
      providers in their institutions. Using multilevel modeling, physicians (OR 2.69,
      p-value < 0.01, 95% CI 1.62-4.57) and surgeons (OR 3.00, p-value < 0.01, 95% CI
      1.52-6.20) both perceived greater benefit of MCCs for coordinating and improving
      patient plans than administrators. Although MCCs appear to positively influence
      patient care and interprofessional interactions, variability exists among cancer
      providers and administrators concerning their acceptance and perceived benefits.
      Further research should concentrate on further probing these trends, and
      exploring explanations and solutions for the inconsistent acceptance of MCCs into
      routine cancer care.

PMID- 19842954
TI  - Performance-based competencies for culturally responsive interprofessional
      collaborative practice.
AB  - This paper will highlight how a literature review and stakeholder-expert feedback
      guided the creation of an interprofessional facilitator-collaborator competency
      tool, which was then used to design an interprofessional facilitator development
      program for the Partners for Interprofessional Cancer Education (PICE) Project.
      Cancer Care Nova Scotia (CCNS), one of the PICE Project partners, uses an
      Interprofessional Core Curriculum (ICC) to provide continuing education workshops
      to community-based practitioners, who as a portion of their practice, care for
      patients experiencing cancer. In order to deliver this curriculum, health
      professionals from a variety of disciplines required education that would enable
      them to become culturally sensitive interprofessional educators in promoting
      collaborative patient-centred practice. The Registered Nurses Professional
      Development Centre (RN-PDC), another PICE Project partner, has expertise in
      performance-based certification program design and utilizes a competency-based
      methodology in its education framework. This framework and methodology was used
      to develop the necessary interprofessional facilitator competencies that
      incorporate the knowledge, skills, and attitudes required for performance. Three
      main competency areas evolved, each with its own set of competencies, performance
      criteria and behavioural indicators.

PMID- 19842955
TI  - The road to collaboration: developing an interprofessional competency framework.
AB  - In the absence of an interprofessional competency framework in Canada, the
      College of Health Disciplines (CHD) at the University of British Columbia
      developed a universally applicable framework. This article discusses the
      development of the "BC Competency Framework for Interprofessional Collaboration".
      Building on a Health Canada funded initiative through the Interprofessional
      Network of British Columbia (In-BC), the CHD compared and contrasted existing
      competency frameworks and consulted curriculum and IP experts throughout British
      Columbia. The resulting framework is designed to inform curriculum development
      for health and human service professionals throughout the continuum of learning,
      starting with pre-licensure education and extending into continuing professional
      development. The framework will serve as a foundation for future curriculum
      reform by health and human service educators, practitioners and decision-makers
      throughout BC and will contribute to the competency literature in Canada.

PMID- 19842956
TI  - Student-led interprofessional education revolution: developing the "Diamond
      Approach".

PMID- 19842957
TI  - Interprofessional interaction, negotiation and non-negotiation on general
      internal medicine wards.
AB  - Research suggests that health care can be improved and patient harm reduced when
      health professionals successfully collaborate across professional boundaries.
      Consequently, there is growing support for interprofessional collaboration in
      health and social care, both nationally and internationally. Factors including
      professional hierarchies, discipline-specific patterns of socialization, and
      insufficient time for teambuilding can undermine efforts to improve
      collaboration. This paper reports findings from an ethnographic study that
      explored the nature of interprofessional interactions within two general and
      internal medicine (GIM) settings in Canada. 155 hours of observations and 47
      interviews were gathered with a range of health professionals. Data were
      thematically analyzed and triangulated. Study findings indicated that both formal
      and informal interprofessional interactions between physicians and other health
      professionals were terse, consisting of unidirectional comments from physicians
      to other health professionals. In contrast, interactions involving nurses,
      therapists and other professionals as well as intraprofessional exchanges were
      different. These exchanges were richer and lengthier, and consisted of
      negotiations which related to both clinical as well as social content. The paper
      draws on Strauss' (1978) negotiated order theory to provide a theoretical lens to
      help illuminate the nature of interaction and negotiation in GIM.

PMID- 19842958
TI  - Professions show different enquiry strategies for elder abuse detection:
      implications for training and interprofessional care.
AB  - In a project to develop and validate a tool to assist family physicians'
      identification of elder abuse, nine prospective questions underwent critique and
      ranking in focus groups comprised of 31 social workers, doctors, and nurses
      working with elder abuse. Differing attitudes to the questions were discernible
      amongst the three professions. The social workers' approach appeared based on
      need to advocate for clients. Nurses' viewpoints seemed influenced by utilitarian
      concerns for practicality and directness, desire to respect doctors' time
      constraints, and discomfort that some physicians' questioning might impose on
      nursing fields of interest. Physicians' concerns tended to be holistic, tempered
      by practicality and time management issues. However despite such differences
      expressed during lengthy group discussions, members of all three professions,
      when asked to independently rank the top five questions, favorably ranked the
      same five (though not necessarily in the same order). Since there are known
      barriers to successful elder abuse enquiry the differences and concerns seen in
      this study may represent another potential obstacle. Programs that address elder
      abuse might therefore consider sensitizing trainees to the potential
      predispositions within their own and their colleagues' professions. This
      proactive strategy might facilitate interprofessional approaches to elder abuse
      detection.

PMID- 19842959
TI  - Integrative health care in a hospital setting: communication patterns between CAM
      and biomedical practitioners.
AB  - Research in the area of collaboration between complementary and alternative
      medicine (CAM) and biomedical practitioners often describes their relationships
      as fraught with power struggles. This paper explores communication among the
      various stakeholders at an integrative health clinic for artists located in a
      university hospital. Qualitative research methods were used, in-depth interviews
      and semi-structured focus groups, to facilitate the gathering of information
      about patterns of communication among stakeholders involved at the clinic. The
      findings describe the challenges to communication and integration at the clinic.
      The lack of communication is described as a scheduling issue, or lack of
      consistent presence of CAM practitioners, and a lack of formal methods of
      communication (patient charting). The consequences of these gaps were felt mostly
      by the CAM practitioners, as their scope of practice was not well understood by
      other practitioners. CAM practitioners stated that this had a direct effect on
      their confidence levels. CAM practitioners were relegated to the periphery of the
      hospital in their role as part-time, contract employees. Their lack of consistent
      presence at the clinic lead to a lack of understanding of their scope of
      practice, hence, a lack of referrals from other health-care practitioners,
      particularly those who were biomedically-oriented.

PMID- 19842960
TI  - Intermediate care: an interprofessional education opportunity in primary care.

PMID- 19842961
TI  - Reflections on facilitating an interprofessional problem-based learning module.

PMID- 19842962
TI  - A participatory approach to interprofessional education research: students
      researching with their peers.

PMID- 19842968
TI  - Selection in ephemeral networks.
AB  - A model of "ephemeral" population structure is presented that applies not only to
      biological systems in which discrete groups form but also to networks without
      group boundaries. The evolution of altruistic behaviors is discussed. Nonrandom
      interaction and nonlinear fitness structures are modeled; together, these factors
      can produce stable polymorphisms of altruistic and selfish types, as well as
      bistability. Empirical applications of the model may be found in microbes, marine
      invertebrates, annual plants, and other organisms.

PMID- 19842969
TI  - A linear model method for biodiversity-ecosystem functioning experiments.
AB  - Experiments that manipulate species richness and measure ecosystem functioning
      attempt to separate the effects of species richness (the number of species) from
      those of species identity. We introduce an experimental design that ensures that
      each species is selected the same number of times at each level of species
      richness. In combination with a linear model analysis, this approach is able to
      unambiguously partition the variance due to different species identities and the
      variance due to nonlinear species richness, a proxy measure for interactions
      among species. Our design and analysis provide several advantages over methods
      that are currently used. First, the linear model method has the potential to
      directly estimate the role of various ecological mechanisms (e.g., competition,
      facilitation) rather than the consequences of those mechanisms (e.g., the
      "complementarity effect"). Second, unlike other methods that are currently used,
      this one is able to estimate the impact of diversity when the contribution of
      individual species in a mixture is unknown.

PMID- 19842970
TI  - Campylobacter jejuni strain CG8421: a refined model for the study of
      Campylobacteriosis and evaluation of Campylobacter vaccines in human subjects.
AB  - BACKGROUND: A robust human challenge model for Campylobacter jejuni is an
      important tool for the evaluation of candidate vaccines. The previously
      established model conveys a potential risk of Guillain-Barre syndrome
      attributable to lipooligosaccharide ganglioside mimicry. This work establishes a
      new C. jejuni human challenge model that uses a strain (CG8421) without
      ganglioside mimicry and that applies Campylobacter-specific cellular immunity
      screening to achieve high attack rates at lower inoculum doses. METHODS: Healthy
      Campylobacter-naive adults participated in an open-label challenge trial.
      Participants were dosed with C. jejuni CG8421 and followed as inpatients. Pattern
      of illness, bacterial shedding, and immunologic responses were determined.
      RESULTS: Following screening, 23 subjects received 1 X 10(6) or 1 X 10(5) colony
      forming units of C. jejuni, with attack rates (percentage of patients who became
      ill) of 100% (1 X 10(6) colony-forming units) or 93% (1 X 10(5) colony-forming
      units). Every subject shed CG8421; the median time to diarrhea onset was 72.3 h
      (interquartile range, 53.9-99.9 h). Symptoms included abdominal cramps (74%),
      nausea (65%), and fever (39%). No major safety concerns occurred, including
      bacteremia, hypotension, or postinfectious sequelae. Unexpectedly, recrudescent
      infection occurred in 2 subjects (1 subject without Campylobacter-specific
      adaptive immune responses and 1 with azithromycin resistance acquired in vivo);
      both infections cleared after receipt of additional antibiotics. Cumulative
      Campylobacter-specific immune responses were as follows: serologic response
      occurred in 87% (immunoglobulin [Ig] A) and 48% (IgG) of subjects, in vitro
      interferon-gamma production occurred in 91% of subjects, and 96% of subjects had
      IgA antibody-secreting cells and fecal IgA detected. CONCLUSIONS: The C. jejuni
      CG8421 challenge model provides a safe and effective tool, without the risk of
      Guillain-Barre syndrome. The model demonstrates high attack rates after lower
      doses of challenge inoculum, provides further understanding of immunologic
      responses, and permits future investigation of candidate Campylobacter vaccines.

PMID- 19842971
TI  - Reasons why emergency department providers do not rely on the pneumonia severity
      index to determine the initial site of treatment for patients with pneumonia.
AB  - BACKGROUND: Many emergency department (ED) providers do not follow guideline
      recommendations for the use of the pneumonia severity index (PSI) to determine
      the initial site of treatment for patients with community-acquired pneumonia
      (CAP). We identified the reasons why ED providers hospitalize low-risk patients
      or manage higher-risk patients as outpatients. METHODS: As a part of a trial to
      implement a PSI-based guideline for the initial site of treatment of patients
      with CAP, we analyzed data for patients managed at 12 EDs allocated to a high
      intensity guideline implementation strategy study arm. The guideline recommended
      outpatient care for low-risk patients (nonhypoxemic patients with a PSI risk
      classification of I, II, or III) and hospitalization for higher-risk patients
      (hypoxemic patients or patients with a PSI risk classification of IV or V). We
      asked providers who made guideline-discordant decisions on site of treatment to
      detail the reasons for nonadherence to guideline recommendations. RESULTS: There
      were 1,306 patients with CAP (689 low-risk patients and 617 higher-risk
      patients). Among these patients, physicians admitted 258 (37.4%) of 689 low-risk
      patients and treated 20 (3.2%) of 617 higher-risk patients as outpatients. The
      most commonly reported reasons for admitting low-risk patients were the presence
      of a comorbid illness (178 [71.5%] of 249 patients); a laboratory value, vital
      sign, or symptom that precluded ED discharge (73 patients [29.3%]); or a
      recommendation from a primary care or a consulting physician (48 patients
      [19.3%]). Higher-risk patients were most often treated as outpatients because of
      a recommendation by a primary care or consulting physician (6 [40.0%] of 15
      patients). CONCLUSION: ED providers hospitalize many low-risk patients with CAP,
      most frequently for a comorbid illness. Although higher-risk patients are
      infrequently treated as outpatients, this decision is often based on the request
      of an involved physician.

PMID- 19842972
TI  - Costs for households and community perception of meningitis epidemics in burkina
      faso.
AB  - Bacterial meningitis in the African meningitis belt remains 1 of the most serious
      threats to health. The perceptions regarding meningitis in local populations and
      the cost of illness for households are not well described. We conducted an
      anthropologic and economic study in Burkina Faso, in the heart of the meningitis
      belt. Respondents reported combining traditional and modern beliefs regarding
      disease etiology, which in turn influenced therapeutic care-seeking behavior.
      Households spent US $90 per meningitis case, or 34% of the annual gross domestic
      product per capita, and up to US $154 more when meningitis sequelae occurred.
      Much of this cost was attributable to direct medical expenses, which in theory
      are paid by the government. Preventive immunization against meningitis will
      overcome limitations imposed by traditional beliefs and contribute to poverty
      reduction goals.

PMID- 19842973
TI  - Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir
      Lamivudine: a randomized, 96-week trial.
AB  - BACKGROUND: There are 2 once-daily, fixed-dose-combination, dual-nucleoside
      analogue tablets: tenofovir 300 mg-emtricitabine 200 mg (TDF-FTC) and abacavir
      600 mg-lamivudine 300 mg (ABC-3TC). Which fixed-dose-combination tablet is more
      effective and safe is uncertain. METHODS: We compared TDF-FTC and ABC-3TC in a
      randomized, open-label, 96-week trial in which either fixed-dose-combination was
      substituted for current nucleoside treatments in human leukocyte antigen-B*5701
      negative adults with human immunodeficiency virus loads <50 copies/mL. The
      primary end point was virological failure (consecutive viral load measurements
      >400 copies/mL, by intention-to-treat). Secondary end points included death,
      AIDS, adverse events, serious non-AIDS events, metabolic parameters, and body
      composition. We used exact statistics for differences in proportions, T tests to
      compare means, and Cox regression for hazard ratios. RESULTS: Of 441 patients who
      were screened, 357 were treated; 98% were men, the mean age was 45 years, 30%
      were receiving TDF, 20% were receiving ABC, and 24% were receiving a protease
      inhibitor. Virological failure was uncommon (5.6% for ABC-3TC and 3.9% for TDF
      FTC; difference, 1.7%; 95% confidence interval [CI], -2.8% to 6.1%; P = .62). No
      participant developed AIDS, whereas 18 (5%) participants developed a serious non
      AIDS event (rate, 2.79 events per 100 person-years; 95% CI, 1.76-4.43), of which
      4 were fatal. TDF-FTC was associated with significantly fewer serious non-AIDS
      events than ABC-3TC (1.2 vs 4.8 events per 100 patient-years; hazard ratio [HR],
      0.24; 95% CI, 0.08-0.73; P = .012), influenced mostly by a lower rate of
      cardiovascular events (0.3 vs 2.2 events per 100 patient-years; HR, 0.12; 95% CI,
      0.02-0.98; P = .048). TDF-FTC resulted in significantly lower bone mineral
      density (mean difference in hip t score, 0.16; 95% CI, 0.08-0.23; P < .001) but
      not in more fractures. CONCLUSIONS: In this population, TDF-FTC and ABC-3TC had
      similar virological efficacy, but ABC-3TC was associated with more serious non
      AIDS events, particularly cardiovascular events. Clinical trials registration.
      NCT00192634 .

PMID- 19842974
TI  - Clinical outcomes in household contacts of patients with cholera in Bangladesh.
AB  - BACKGROUND: Multiple Vibrio cholerae infections in the same household are common.
      The objective of this study was to examine the incidence of V. cholerae infection
      and associated clinical symptoms in household contacts of patients with cholera
      and to identify risk factors for development of severe dehydration in this
      cohort. METHODS: Household contacts of hospitalized patients with cholera were
      observed with frequent clinical assessments and collection of serum and rectal
      swab samples for culture for a period of 21 days after presentation of the index
      case. RESULTS: One-half (460 of 944) of all contacts reported diarrhea during the
      study period, and symptoms most frequently began 2 days after presentation of the
      index case. Antibiotics were used by 199 (43%) of 460 contacts with diarrhea.
      Results of rectal swab cultures for V. cholerae were positive for 202 (21%) of
      944 contacts, and 148 (73%) infected contacts experienced diarrhea. Significant
      dehydration developed in 26 contacts; predictors of dehydration included
      vomiting, each additional day of diarrhea, and blood group O status. CONCLUSIONS:
      In urban Bangladesh, the burden of diarrheal illness among household contacts of
      patients with cholera is higher than was previously estimated, and prophylactic
      intervention is feasible, because the majority of symptomatic cases of V.
      cholerae infection in contacts begin soon after presentation of the index case.
      Re-evaluation of targeted chemoprophylaxis for household contacts of patients
      with cholera may be warranted.

PMID- 19842975
TI  - Fusobacterium necrophorum: most prevalent pathogen in peritonsillar abscess in
      Denmark.
AB  - BACKGROUND: Group A streptococci are commonly regarded as the most prevalent
      cause of acute bacterial tonsillitis and peritonsillar abscess (PTA). However,
      the majority of PTA aspirates also contain strains of anaerobes, and accumulating
      evidence indicates that Fusobacterium necrophorum (FN) could be involved in acute
      tonsillitis. The purpose of the present study was to describe the epidemiology
      and bacteriology of PTA in Denmark, with particular emphasis on correlations
      between microbiological, clinical, and laboratory data. METHODS: A retrospective
      study on all patients with PTA admitted to the ear, nose, and throat department
      at Aarhus University Hospitals from January 2001 through December 2006 was
      conducted. RESULTS: In total, 847 patients were included in the study. The mean
      annual incidence of PTA was 41 cases/100,000 population. FN was the most
      frequently detected bacteria (in 23% of cultures), followed by group A
      streptococci (in 17%) and groups C and G streptococci (counted together, in 5%).
      Of the 191 FN isolates detected, 155 (81%) grew as pure culture. Patients
      infected with FN were significantly younger than patients infected with other
      strains of bacteria (P < .001). Patients with FN exhibited significantly higher
      neutrophil counts (P < .001) and C-reactive protein values (P = .01) than did
      patients infected with other bacteria. CONCLUSIONS: To our knowledge, this study
      is the first report of FN being the most prevalent pathogen in PTA patients. The
      significantly higher neutrophil counts and C-reactive protein values strongly
      indicate the pathogenic importance of FN in PTA. The widespread reliance on rapid
      streptococcal antigen test in general practice to appoint patients for
      antibiotics and the highest PTA incidence ever reported raise concern that highly
      virulent bacteria may be left initially untreated.

PMID- 19842976
TI  - The European surveillance of antimicrobial consumption (ESAC) point-prevalence
      survey of antibacterial use in 20 European hospitals in 2006.
AB  - BACKGROUND: Point-prevalence surveys have been used to document antimicrobial use
      in hospitals for >20 years. However, published surveys are inconsistent with
      respect to population, indication, and the details of therapy that were included.
      We aimed to standardize a method for surveillance of antibacterial use in
      hospitals from different health care systems and to identify targets for quality
      improvement. METHODS: We adapted a Web-based reporting system from STRAMA, the
      Swedish Strategic Programme against antibiotic resistance. One hospital from each
      of 20 countries took part in the survey, which was completed during 2 calendar
      weeks during 1 April 2006 through 31 May 2006. The survey included all inpatient
      beds for adults and children and identified all patients who were receiving
      systemic antibacterial treatments on the day of survey and all patients who had
      received antibacterial prophylaxis for surgery on the previous day. RESULTS: On
      the day of survey there were 11,571 inpatients in the 20 participating hospitals,
      of whom 30.1% were receiving antibacterial treatment (range, 19%-59%). The most
      common anatomic sites of infection for which antibacterials were prescribed were
      respiratory tract (24%); skin, bone, and joint (18%); intra-abdominal organs
      (16%); and urinary tract (11%). The following 3 quality indicators were
      identified: indication documented in case notes (64%), prophylaxis for surgery
      not continued for >24 h (60%), and therapy for community-acquired pneumonia not
      including third-generation cephalosporins or quinolones (78.5%). CONCLUSION: A
      Web-based method for a point-prevalence survey was successfully piloted in 20
      hospitals across Europe and offers a standardized instrument that can identify
      targets for quality improvement.

PMID- 19842977
TI  - Factors determining serologic response to treatment in patients with syphilis.
AB  - BACKGROUND: The goal of this study was to describe the clinical and epidemiologic
      manifestations of a syphilis outbreak in downtown Madrid, Spain. Because human
      immunodeficiency virus (HIV)-positive patients may be at increased risk of
      serologic failure during syphilis treatment, analysis of factors determining the
      response to treatment was performed in a cohort of HIV-positive and HIV-negative
      patients with syphilis. METHODS: We performed a longitudinal, retrospective study
      of patients with syphilis who received the diagnosis at a university-affiliated
      hospital in Madrid from 2003 through 2007. RESULTS: Three hundred forty-seven
      cases of syphilis were identified and treated (30 primary, 164 secondary, 77
      early latent, and 76 late cases of syphilis). Forty-one percent of patients were
      immigrants, mostly from South America and the Caribbean, and 49.3% were known to
      be HIV positive. Syphilis incidence increased from 15.6 to 35 cases per 100,000
      person-years from 2003 to 2007. Most patients were men, and 50.4% were men who
      had sex with other men. Meningitis (4.9%) and uveitis (2.9%) were the
      complications most frequently observed, and their frequency did not differ
      between HIV-positive and HIV-negative patients. Serologic failure was observed in
      44 (23.5%) patients: 37 (29.6%) of 125 HIV-positive patients and 7 (11.2%) of 62
      HIV-negative patients (odds ratio, 3.3; 95% confidence interval, 1.38-7.93; P <
      .05). Men (hazard ratio [HR], 0.38), patients in the late stage of syphilis (HR,
      0.46), and HIV-positive persons (HR, 0.61) demonstrated slower serological
      responses to treatment. HIV-negative patients responded more frequently to
      treatment, but after 2 years of follow-up, both groups shared similar response
      rates. Antiretroviral treatment reduced the time to serologic response (HR, 2.08;
      95% confidence interval, 1.35- 3.20; P < .001). CONCLUSION: Syphilis incidence
      rose 223% from 2003 to 2007, affecting mostly HIV-positive men, men who have sex
      with men, and immigrants. Men, patients in the late stages of syphilis, and HIV
      positive persons may be at increased risk of serologic failure. Antiretroviral
      therapy significantly reduced the time to achieve response to syphilis treatment
      in HIV-positive patients.

PMID- 19842978
TI  - The art of managing human immunodeficiency virus infection: a balancing act.

PMID- 19842979
TI  - Health care transmission of a newly emergent adenovirus serotype in health care
      personnel at a military hospital in Texas, 2007.
AB  - BACKGROUND: Adenoviruses can cause outbreaks of febrile respiratory illness in
      military trainees, but until 2007, adenovirus serotype 14 (Ad14) was never
      associated with such outbreaks. From April through June 2007, 15 trainees at one
      base were hospitalized for pneumonia due to Ad14. Subsequent reports of febrile
      respiratory illness among health care personnel suggested nosocomial
      transmission. METHODS: Health care personnel participants completed a
      questionnaire and provided blood and nasal wash specimens for Ad14 diagnostic
      testing. We defined a confirmed case of Ad14 infection as one with titers > or =
      1:80 or nasal wash specimens positive for Ad14 by polymerase chain reaction,
      whereas a possible case was defined by titers of 1:20 or 1:40. We also collected
      environmental samples. RESULTS: Among 218 tested health care personnel, 35 (16%)
      had titers > or = 1:20; of these, 7 had possible cases and 28 had confirmed cases
      of infection. Confirmed case patients were more likely to report febrile
      respiratory illness (57% vs 11%; P< .001) and to have had direct contact with
      patients with Ad14 infection (82% vs 62%; P.04 ). Of the 23 confirmed case
      patients with direct contact with Ad14-infected patients, 52% reported that
      patients were not in contact and droplet precautions at the time of exposure.
      Ad14 was recovered from several hospital surfaces. CONCLUSION: Our findings of
      possible nosocomial transmission of Ad14 highlight the need to reinforce
      infection control guidelines.

PMID- 19842980
TI  - Vaccination of solid-organ transplantation candidates.
AB  - Verifying immunization status and updating vaccinations are important steps in
      the evaluation of patients who are solid-organ transplant candidates because the
      potential benefits of vaccination outweigh the risk of adverse events. Because
      patients with end-organ disease, such as end-stage renal disease and cirrhosis,
      have reduced immune responses to many vaccines, vaccination should be performed
      as early as possible during the course of these diseases. Furthermore, it is
      particularly important for live vaccines to be updated during the pretransplant
      assessment because such vaccines are contraindicated once a patient is maintained
      on immunosuppression. Current information on vaccination for adult solid-organ
      transplant candidates is reviewed.

PMID- 19842981
TI  - Topical antimicrobial therapy for treating chronic wounds.
AB  - Various agents have been applied topically to treat infected wounds for
      millennia, but their proper role remains unclear. Topical therapy affords many
      potential advantages but also has disadvantages. Opinions differ on which
      clinical signs define wound infection and on whether quantitative microbiological
      studies are useful. Clinically infected wounds usually require systemic
      antibiotic therapy, whereas clinically uninfected wounds that are healing as
      expected do not require antimicrobials. There is controversy over how to treat
      poorly healing wounds with "secondary" signs suggesting infection; these may
      benefit from topical antimicrobial agents. Some evidence supports using topical
      agents for malodorous or burn wounds. Meta-analyses and systematic reviews
      suggest there are few proven indications for topical antimicrobials. Use of a
      newer, relatively nontoxic antiseptic (eg, cadexomer iodine or silver dressings)
      is preferable to use of topical antibiotics, especially agents that are available
      for systemic use. We provide clinically relevant information on currently
      available topical antimicrobial agents.

PMID- 19842983
TI  - On the effects of signal acuity in a multi-alternative model of decision making.
AB  - We consider the effects of signal sharpness or acuity on the performance of
      neural models of decision making. In these models, a vector of signals is
      presented, and the subject must decide which of the elements of the vector is the
      largest. McMillen and Holmes ( 2006 ) derived asymptotically optimal tests under
      the assumption that the elements of the signal vector were all equal except one.
      In this letter, we consider the case of signals spread around a peak. The acuity
      is a measure of how strongly peaked the signal is. We find that the optimal test
      is one in which the detectors are passed through an output layer that encodes
      knowledge of the possible shapes of the incoming signals. The incorporation of
      such an output layer can lead to significant improvements in decision-making
      tasks.

PMID- 19842982
TI  - Meta-analysis: increased mortality associated with hepatitis C in HIV-infected
      persons is unrelated to HIV disease progression.
AB  - BACKGROUND: It is unclear whether coinfection with hepatitis C virus (HCV)
      increases mortality in patients with human immunodeficiency virus (HIV) infection
      during the era of highly active antiretroviral therapy (HAART). With use of a
      meta-analysis, we estimated the effect of HCV infection on HIV disease
      progression and overall mortality in the pre-HAART and HAART eras. METHOD: The
      PubMed and EMBASE databases were searched for studies published through 30 April
      2008. Additional studies were identified from cited references. Studies reporting
      disease progression or mortality among HCV-HIV coinfected patients were selected.
      Cross-sectional studies, studies without HCV-negative control subjects, and
      studies involving children and/or patients who had undergone liver
      transplantation were excluded. Two authors reviewed articles and extracted data
      on the demographic characteristics of study populations and risk estimates. Meta
      regression was used to explore heterogeneity. RESULTS: Ten studies from the pre
      HAART era and 27 studies from the HAART era were selected. In the pre-HAART era,
      the risk ratio for overall mortality among patients with HCV-HIV coinfection,
      compared with that among patients with HIV infection alone, was 0.68 (95%
      confidence interval [CI], 0.53-0.87). In the HAART era, the risk ratio was 1.12
      (95% CI, 0.82-1.51) for AIDS-defining events and 1.35 (95% CI, 1.11-1.63) for
      overall mortality among coinfected patients, compared with that among patients
      with HIV monoinfection. CONCLUSIONS: HCV coinfection did not increase mortality
      among patients with HIV infection before the introduction of HAART. In contrast,
      in the HAART era, HCV coinfection, compared with HIV infection alone, increases
      the risk of mortality, but not the risk of AIDS-defining events. Future studies
      should determine whether successful treatment of HCV infection could reduce this
      excess risk of mortality in coinfected patients.

PMID- 19842984
TI  - Precise capacity analysis in binary networks with multiple coding level inputs.
AB  - We compute retrieval probabilities as a function of pattern age for networks with
      binary neurons and synapses updated with the simple Hebbian learning model
      studied in Amit and Fusi ( 1994 ). The analysis depends on choosing a neural
      threshold that enables patterns to stabilize in the neural dynamics. In contrast
      to most earlier work, where selective neurons for each pattern are drawn
      independently with fixed probability f, here we analyze the situation where f is
      drawn from some distribution on a range of coding levels. In order to set a
      workable threshold in this setting, it is necessary to introduce a simple
      inhibition in the neural dynamics whose magnitude depends on the total activity
      of the network. Proper choice of the threshold depends on the value of the
      covariances between the synapses for which we provide an explicit formula.
      Retrieval probabilities depend on the distribution of the fields induced by a
      learned pattern. We show that the field induced by the first learned pattern
      evolves as a Markov chain during subsequent learning epochs, leading to a
      recursive formula for the distribution. Alternatively, the distribution can be
      computed using a normal approximation, which involves the value of the synaptic
      covariances. Capacity is computed as the sum of the retrieval probabilities over
      all ages. We show through simulation that the chosen threshold enables retrieval
      with asynchronous dynamics even in the presence of significant noise in the
      initial state of the pattern. The computed probabilities with both methods are
      shown to be very close to probabilities estimated from simulation. The analysis
      is extended to randomly connected networks.

PMID- 19842985
TI  - Dynamics and robustness of familiarity memory.
AB  - When presented with an item or a face, one might have a sense of recognition
      without the ability to recall when or where the stimulus has been encountered
      before. This sense of recognition is called familiarity memory. Following
      previous computational studies of familiarity memory, we investigate the
      dynamical properties of familiarity discrimination and contrast two different
      familiarity discriminators: one based on the energy of the neural network and the
      other based on the time derivative of the energy. We show how the familiarity
      signal decays rapidly after stimulus presentation. For both discriminators, we
      calculate the capacity using mean field analysis. Compared to recall capacity
      (the classical associative memory in Hopfield nets), both the energy and the
      slope discriminators have bigger capacity, yet the energy-based discriminator has
      a higher capacity than one based on its time derivative. Finally, both
      discriminators are found to have a different noise dependence.

PMID- 19842986
TI  - How to modify a neural network gradually without changing its input-output
      functionality.
AB  - It is generally unknown when distinct neural networks having different synaptic
      weights and thresholds implement identical input-output transformations.
      Determining the exact conditions for structurally distinct yet functionally
      equivalent networks may shed light on the theoretical constraints on how diverse
      neural circuits might develop and be maintained to serve identical functions.
      Such consideration also imposes practical limits on our ability to uniquely infer
      the structure of underlying neural circuits from stimulus-response measurements.
      We introduce a biologically inspired mathematical method for determining when the
      structure of a neural network can be perturbed gradually while preserving
      functionality. We show that for common three-layer networks with convergent and
      nondegenerate connection weights, this is possible only when the hidden unit
      gains are power functions, exponentials, or logarithmic functions, which are
      known to approximate the gains seen in some biological neurons. For practical
      applications, our numerical simulations with finite and noisy data show that
      continuous confounding of parameters due to network functional equivalence tends
      to occur approximately even when the gain function is not one of the
      aforementioned three types, suggesting that our analytical results are applicable
      to more general situations and may help identify a common source of parameter
      variability in neural network modeling.

PMID- 19842987
TI  - Growing self-organizing surface map: learning a surface topology from a point
      cloud.
AB  - The growing self-organizing surface map (GSOSM) is a novel map model that learns
      a folded surface immersed in a 3D space. Starting from a dense point cloud, the
      surface is reconstructed through an incremental mesh composed of approximately
      equilateral triangles. Unlike other models such as neural meshes (NM), the GSOSM
      builds a surface topology while accepting any sequence of sample presentation.
      The GSOSM model introduces a novel connection learning rule called competitive
      connection Hebbian learning (CCHL), which produces a complete triangulation.
      GSOSM reconstructions are accurate and often free of false or overlapping faces.
      This letter presents and discusses the GSOSM model. It also presents and analyzes
      a set of results and compares GSOSM with some other models.

PMID- 19842988
TI  - Cross-correlations in high-conductance states of a model cortical network.
AB  - Neuronal firing correlations are studied using simulations of a simple network
      model for a cortical column in a high-conductance state with dynamically balanced
      excitation and inhibition. Although correlations between individual pairs of
      neurons exhibit considerable heterogeneity, population averages show systematic
      behavior. When the network is in a stationary state, the average correlations are
      generically small: correlation coefficients are of order 1/N, where N is the
      number of neurons in the network. However, when the input to the network varies
      strongly in time, much larger values are found. In this situation, the network is
      out of balance, and the synaptic conductance is low, at times when the strongest
      firing occurs. However, examination of the correlation functions of synaptic
      currents reveals that after these bursts, balance is restored within a few
      milliseconds by a rapid increase in inhibitory synaptic conductance. These
      findings suggest an extension of the notion of the balanced state to include
      balanced fluctuations of synaptic currents, with a characteristic timescale of a
      few milliseconds.

PMID- 19842989
TI  - Supervised learning in spiking neural networks with ReSuMe: sequence learning,
      classification, and spike shifting.
AB  - Learning from instructions or demonstrations is a fundamental property of our
      brain necessary to acquire new knowledge and develop novel skills or behavioral
      patterns. This type of learning is thought to be involved in most of our daily
      routines. Although the concept of instruction-based learning has been studied for
      several decades, the exact neural mechanisms implementing this process remain
      unrevealed. One of the central questions in this regard is, How do neurons learn
      to reproduce template signals (instructions) encoded in precisely timed sequences
      of spikes? Here we present a model of supervised learning for biologically
      plausible neurons that addresses this question. In a set of experiments, we
      demonstrate that our approach enables us to train spiking neurons to reproduce
      arbitrary template spike patterns in response to given synaptic stimuli even in
      the presence of various sources of noise. We show that the learning rule can also
      be used for decision-making tasks. Neurons can be trained to classify categories
      of input signals based on only a temporal configuration of spikes. The decision
      is communicated by emitting precisely timed spike trains associated with given
      input categories. Trained neurons can perform the classification task correctly
      even if stimuli and corresponding decision times are temporally separated and the
      relevant information is consequently highly overlapped by the ongoing neural
      activity. Finally, we demonstrate that neurons can be trained to reproduce
      sequences of spikes with a controllable time shift with respect to target
      templates. A reproduced signal can follow or even precede the targets. This
      surprising result points out that spiking neurons can potentially be applied to
      forecast the behavior (firing times) of other reference neurons or networks.

PMID- 19842990
TI  - Derivatives of logarithmic stationary distributions for policy gradient
      reinforcement learning.
AB  - Most conventional policy gradient reinforcement learning (PGRL) algorithms
      neglect (or do not explicitly make use of) a term in the average reward gradient
      with respect to the policy parameter. That term involves the derivative of the
      stationary state distribution that corresponds to the sensitivity of its
      distribution to changes in the policy parameter. Although the bias introduced by
      this omission can be reduced by setting the forgetting rate gamma for the value
      functions close to 1, these algorithms do not permit gamma to be set exactly at
      gamma = 1. In this article, we propose a method for estimating the log stationary
      state distribution derivative (LSD) as a useful form of the derivative of the
      stationary state distribution through backward Markov chain formulation and a
      temporal difference learning framework. A new policy gradient (PG) framework with
      an LSD is also proposed, in which the average reward gradient can be estimated by
      setting gamma = 0, so it becomes unnecessary to learn the value functions. We
      also test the performance of the proposed algorithms using simple benchmark tasks
      and show that these can improve the performances of existing PG methods.

PMID- 19842991
TI  - Spiking neuron model for temporal sequence recognition.
AB  - A biologically inspired neuronal network that stores and recognizes temporal
      sequences of symbols is described. Each symbol is represented by excitatory input
      to distinct groups of neurons (symbol pools). Unambiguous storage of multiple
      sequences with common subsequences is ensured by partitioning each symbol pool
      into subpools that respond only when the current symbol has been preceded by a
      particular sequence of symbols. We describe synaptic structure and neural
      dynamics that permit the selective activation of subpools by the correct
      sequence. Symbols may have varying durations of the order of hundreds of
      milliseconds. Physiologically plausible plasticity mechanisms operate on a time
      scale of tens of milliseconds; an interaction of the excitatory input with
      periodic global inhibition bridges this gap so that neural events representing
      successive symbols occur on this much faster timescale. The network is shown to
      store multiple overlapping sequences of events. It is robust to variation in
      symbol duration, it is scalable, and its performance degrades gracefully with
      perturbation of its parameters.

PMID- 19842992
TI  - Association of glutathione-S-transferase polymorphisms with atopic dermatitis
      risk in preschool age children.
AB  - BACKGROUND: Glutathione S-transferase (GST) enzymes are critical for detoxifying
      reactive oxygen species (ROS) and their products which have been implicated in
      the pathology of inflammatory diseases such as atopic dermatitis (AD). METHODS:
      We investigated the effects of genetic polymorphisms of GST on the risk of AD in
      preschool age children. Biomarkers for oxidative stress were also evaluated with
      respect to GST genotype. RESULTS: The GSTP1 Val105 allele was significantly
      associated with an increased risk of AD [odds ratio (OR)=1.62, p<0.05]. The
      combination of the GSTP1 Val105 allele and the GSTT1 null genotype further
      increased this risk by 2.3-fold (p<0.01). No association was observed for the
      GSTM1 null or GSTT1 null genotype alone. In children with AD, blood total
      antioxidant capacity was significantly less (p<0.001), while malondialdehyde was
      higher (p=0.12). Children with the GSTP1 Val105 allele had significantly lower
      concentrations of erythrocyte glutathione compared to GSTP1 ILE/ILE homozygotes
      (P=0.03). CONCLUSIONS: Our study suggests that the GSTP1 Val105 allele is an
      important determinant of susceptibility to AD in preschool age children and
      increased oxidative stress may play a role in the pathogenesis of AD.

PMID- 19842993
TI  - Antibodies to mutated citrullinated vimentin and antibodies to cyclic
      citrullinated peptides in juvenile idiopathic arthritis.
AB  - BACKGROUND: The goal of the study was to assess the presence of antibodies to
      mutated citrullinated vimentin (anti-MCV) and cyclic citrullinated peptides (anti
      CCP) in patients with juvenile idiopathic arthritis (JIA) compared with patients
      with other juvenile onset rheumatic diseases. METHODS: The study included 56
      patients who fulfilled the International League of Associations for Rheumatology
      (ILAR) classification criteria for JIA, and 17 control patients with other
      juvenile onset rheumatic diseases. Data on six core outcome variables and the
      Sharp score were collected for patients with JIA. Sera and synovial fluid, if
      available, were tested for anti-CCP and anti-MCV antibodies using a commercial
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Anti-MCV antibodies were
      positive in 3/56 (5.4%) and anti-CCP in 1/56 (1.8%) of patients with JIA. Two out
      of three anti-MCV positive patients (one of them also anti-CCP positive) were
      found to be rheumatoid factor (RF)-positive with polyarticular disease. Within
      the control group, anti-MCV was positive in 4/17 (23.5%) patients, while anti-CCP
      positivity was not observed. No correlation between anti-MCV with anti-CCP
      antibody levels was found for any of the six core outcome variables or for the
      adapted Sharp score. CONCLUSIONS: Our results show that antibodies targeting
      citrullinated proteins are not a useful diagnostic marker for JIA, but can
      indicate severe patterns of disease in JIA.

PMID- 19842994
TI  - Screening for M-proteinemia: serum protein electrophoresis and free light chains
      compared.
AB  - BACKGROUND: The objective of this study was to evaluate the efficiency of free
      light chain (FLC) analysis in comparison to serum protein electrophoresis (SPE)
      for detecting M-proteinemia. METHODS: A total of 553 consecutive patients for
      whom evaluation of M-proteinemia was requested were included in this study. For
      all patients, serum FLC analysis and SPE followed by pentavalent immunofixation
      analysis was performed. Identification of monoclonal bands was performed using
      specific antisera. FLC analysis was performed using the Modular P analyzer in
      accordance with the manufacturer's recommendations. Local reference ranges for
      FLCs on this platform were established based on samples from patients with a
      normal electrophoretic pattern [no monoclonal bands, no hypo- or
      hypergammaglobulinemia, no acute phase pattern and normal kidney function, i.e.,
      estimated glomerular filtration rate (eGFR) >60 mL/min]. RESULTS: Local reference
      ranges (95%) were established (n=243): kappa: 8.01-28.26 mg/L; lambda: 8.07-23.58
      mg/L and kappa/lambda ratio: 0.74-1.66. Negative and positive predictive values
      were 98.6% and 49.5%, respectively, for screening for M-proteinemia by SPE alone,
      94.3% and 21.7% for FLC concentration and 95.1% and 21.4% for FLC with the
      kappa/lambda-ratio included. Combining protein electrophoresis and FLCs resulted
      in a negative predictive value of 99.0% and a positive predictive value of 23.4%.
      CONCLUSIONS: Serum FLC analysis alone is not suitable for screening for M
      proteinemia.

PMID- 19842995
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      assay for serum 25-hydroxyvitamin D2/D3 using a turbulent flow online extraction
      technology.
AB  - BACKGROUND: Vitamin D is important to health and disease. Liquid chromatography
      tandem mass spectrometry (LC-MSMS) is considered the most accurate technology for
      quantification of serum 25-hydroxyvitamin D (25OHD) which is the best biomarker
      for estimating vitamin D nutritional status. METHODS: Serum was mixed with
      acetonitrile containing hexadeuterated 25-hydroxyvitamin D(3) (d(6)-25OHD3) and
      centrifuged 10 min at 15,634Xg. The supernatant was injected onto a turbulent
      flow preparatory column then transferred to a polar endcapped C18 analytical
      column. The mass spectrometer was set for positive atmospheric pressure chemical
      ionization. RESULTS: The analytical cycle time was 5.5 min. Inter- and intra
      assay CV for both analytes across three concentrations ranged from 3.8% to 14.2%.
      The method was linear from 3.0 to 283.6 nmol/L for 25-hydroxyvitamin D(3)
      (25OHD3) and 4.6 to 277.9 nmol/L for 25-hydroxyvitamin D(2) (25OHD2), with an
      accuracy of 88.7%-118.7% and 90.7%-100.3%, respectively. No carryover or ion
      suppression was observed. Comparison with a radioimmunoassay using patient
      specimens (n=527) showed a mean difference of 5.2%, and diagnostic agreement of
      80.9% with Deming regression of slope 0.867, intercept 12.8, standard error of
      estimate (SEE) 17.4, and r=0.8425. CONCLUSIONS: The LC-MSMS method coupled with
      turbulent flow technology for serum 25OHD quantitation is rapid, efficient, and
      suitable for clinical testing.

PMID- 19842997
TI  - Haemoglobin fluctuations in patients on haemodialysis treated with ESAs: clinical
      observations from two centres.
AB  - BACKGROUND: The purpose of this analysis was to quantify haemoglobin (Hb)
      variability in patients receiving haemodialysis (HD) and erythropoiesis
      stimulating agent (ESA) treatment from data independently collected in two
      different geographical settings. STUDY DESIGN, SETTINGS AND PATIENTS: Two studies
      retrospectively reviewed patients undergoing HD and stable ESA treatment at
      centres in Australia and the UK (56 and 154 patients, respectively). Monthly Hb
      values were obtained over a 12-month period. The frequency, duration, amplitude
      and direction of Hb fluctuations (Hb outside the range 11-12 g/dl in the
      Australian data-set and 11-12.5 g/dl in the UK data-set) were evaluated. RESULTS:
      The overall mean Hb level was 11.27 and 11.71 g/dl in the Australian and UK data
      set, respectively. All patients experienced > or =1 Hb fluctuation and 68-73% had
      > or =3 fluctuations over the study period. Upward and downward Hb fluctuations
      occurred with similar frequency and were of similar amplitude. Fluctuations of
      more extreme amplitude (high amplitude fluctuations) were more common than
      fluctuations of lesser amplitude. The total duration of time spent outside the Hb
      range (mean +/- standard deviation) was 8.6 +/- 2.5 and 7.4 +/- 2.5 months in the
      Australian and UK data-set, respectively. The total duration with Hb <11 g/dl was
      3.7 +/- 3.0 and 3.7 +/- 2.7 months, respectively. Most patients (95%) required
      ESA dose adjustment; the median number of dose adjustments per patient was 2
      (range 0-5). CONCLUSIONS: Despite the study limitations of retrospectivity and
      its cross-sectional nature, the reported observations that Hb fluctuations
      outside target ranges occur frequently in patients on HD receiving ESAs are
      clearly confirmed and were strikingly similar in the two different geographical
      locations.

PMID- 19842996
TI  - From somatostatin to octreotide LAR: evolution of a somatostatin analogue.
AB  - BACKGROUND: Acromegaly is characterized by overproduction of growth hormone (GH)
      by the pituitary gland. GH stimulates the synthesis of insulin-like growth factor
      I (IGF-I), and the somatic growth and metabolic dysfunction that characterize
      acromegaly are a consequence of elevated GH and IGF-I levels.
      Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, slow-growing
      neoplasms that have usually metastasized by the time of diagnosis. The majority
      of GEP-NETs are carcinoid tumors whose syndrome is caused by the hypersecretion
      of biogenic amines, peptides and polypeptides responsible for the principal
      symptoms of diarrhea and flushing. METHODS: The MEDLINE and EMBASE databases were
      searched for preclinical and clinical studies of octreotide (Sandostatin* ), a
      potent synthetic somatostatin analogue, in patients with acromegaly or GEP-NETs.
      OBJECTIVE: This article reviews the 20 years of clinical experience with
      octreotide and the impact it has made in patients with acromegaly or GEP-NETs.
      RESULTS: Octreotide has proven to be an essential component in the management
      strategy of acromegaly and GEP-NETs over the past 20 years. The multiple
      beneficial effects of octreotide throughout the body, combined with its
      established safety profile (the most common adverse effects are injection-site
      pain and gastrointestinal events), have made it an appealing option for
      clinicians. The advent of the long-acting release (LAR) formulation of octreotide
      provided additional benefits to patients through monthly administration, while
      maintaining the efficacy and tolerability profile of the daily subcutaneous
      formulation. CONCLUSIONS: Octreotide is a potent synthetic somatostatin analogue
      that has become the mainstay of medical therapy for tumor control in
      neuroendocrine disorders such as acromegaly and GEP-NETs. The development of
      octreotide LAR offered a further advancement; less frequent dosing provided
      valuable benefits in quality of life to patients, with equivalent efficacy and
      tolerability. Moreover, recent results from the PROMID study have confirmed the
      antiproliferative effect of octreotide LAR in patients with well-differentiated
      metastatic GEP-NETs of the midgut. New therapeutic uses of octreotide are
      currently under investigation in a variety of clinical settings.

PMID- 19842998
TI  - Potential neuroprotection mechanisms in PD: focus on dopamine agonist
      pramipexole.
AB  - BACKGROUND: The death of dopaminergic neurons in Parkinson's disease (PD) appears
      to have various causes, including oxidative stress, excitotoxicity, mitochondrial
      dysfunction (and associated apoptosis), ubiquitin/proteasomal dysfunction, and
      inflammation, any of which could in principle be the therapeutic target of a
      neuroprotective drug. The biology of dopaminergic neurons offers further
      potential targets, involving neurotrophic factors, dopamine-neuron genes, and
      even neurogenesis. OBJECTIVE: To outline each hypothetical neuroprotective
      mechanism, the evidence suggesting its relevance to PD, and the research on
      pharmacologic intervention. METHODS: A PubMed search was conducted to identify
      relevant preclinical and clinical literature published between 1989 and 2009.
      Additional articles were identified by reviewing the reference lists of papers
      selected in the original search. To circumscribe the survey and facilitate
      consideration of the conditions required for a neuroprotective effect, emphasis
      was placed on a single drug class, dopamine agonists, and in particular
      pramipexole. REVIEW OF THE FIELD: In a variety of in vitro and in vivo PD models,
      pramipexole exhibited preclinical evidence of neuroprotective actions of all
      hypothesized types, and in human neuroimaging studies it slowed the rate of loss
      of markers of dopaminergic function, consistent with drug-conferred
      neuroprotection in PD itself. Interpretation of the preclinical data was hampered
      by differences among models and by uncertainties concerning each model's mimicry
      of PD. Overall, the identified neuroprotection almost always required
      pretreatment (i.e., before insult) and high drug concentration. Interpretation of
      the clinical data was hampered by absence of placebo control and of a direct
      measure of neuroprotection. CONCLUSIONS: Although the evidence is promising,
      neuroprotection in PD remains an elusive goal. In whatever form it emerges,
      neuroprotective therapy would be a strong argument against deferring PD treatment
      until symptoms are a significant life impediment, and thus would add urgency to
      early PD identification.

PMID- 19842999
TI  - First trimester PAPP-A levels associated with early prediction of pregnancy
      induced hypertension.
AB  - OBJECTIVE: Previous studies have suggested an association between low levels of
      first trimester serum Pregnancy Associated Plasma Protein-A (PAPP-A) and the
      occurrence of hypertension in pregnancy (PIH). The purpose of this study was to
      determine the predictive value of maternal PAPP-A levels in the identification of
      women at risk of PIH. METHODS: Maternal serum PAPP-A was measured between 11-13 +
      6 wks' gestation, as part of the first trimester screening of aneuploidies. Our
      study included only singleton pregnancies (973 cases) over a three years period.
      PAPP-A levels were expressed as gestational age-specific multiples of the median
      (MoM). Hypertension in pregnancy was documented by standard criteria. RESULTS:
      One hundred and eleven pregnant women developed hypertension (8.9%). In these
      patients, PAPP-A levels ranged from 0.53 to 1.08 MoM. After performing a backward
      stepwise regression equation and a ROC curve procedure, a PAPP-A MoM value <0.8
      was able to significantly predict PIH (p < 0.001, area under the ROC curve 83%,
      sensitivity 68%, specificity 86%, 95 degrees CI 0.57-0.94). CONCLUSION: Low
      levels of serum PAPP-A (?0.8 MoM) may be a potential resource in order to early
      screen pregnant women at increased risk of hypertension in pregnancy.

PMID- 19843000
TI  - A randomised, double-blinded, placebo-controlled study of the phosphodiesterase
      type 5 inhibitor sildenafil for the treatment of preeclampsia.
AB  - OBJECTIVE: To determine if the phosphodiesterase type 5 inhibitor sildenafil
      prolongs pregnancy in women with preeclampsia. METHODS: Women with preeclampsia
      at gestational ages 24-34 weeks were recruited from nine hospitals in the UK, and
      randomly assigned to sildenafil citrate or placebo. Medication was increased
      every 3 days from 20 mg three times daily (tid), to 40 mg, and 80 mg tid. The
      primary endpoint was prolongation of pregnancy from randomisation to delivery
      (days). Secondary endpoints were markers of maternal disease and cord pH at
      delivery and infant weight. Details of all adverse events were also collected.
      Plasma samples were taken to establish pharmacokinetic information. Data analysed
      on a modified intention to treat analysis. The study had a power of >95% to
      detect a difference of 5 days. RESULTS: Of 35 women, 17 were allocated to
      sildenafil and 18 to placebo. There was no difference in time from randomisation
      to delivery in the two treatment groups, with a median time of 4 days (range 1
      15) in the sildenafil group and 4.5 days (range 1-30) in the placebo group.
      Sildenafil achieved maximum drug concentrations of 48 ng/ml, 88 ng/ml, and 271
      ng/ml after 3 days of 20 mg, 40 mg and 80 mg tid, respectively. CONCLUSION: We
      have safely conducted a clinical trial of a drug not routinely used during
      pregnancy. Sildenafil in the escalating dose regimen 20-80 mg tid was well
      tolerated, with no increase in maternal or fetal morbidity or mortality but did
      not prolong pregnancy duration in women with preeclampsia. (ClinicalTrials.gov
      number, NCT 00141310).

PMID- 19843001
TI  - The changes of plasma malondialdehyde, nitric oxide, and adrenomedullin levels in
      patients with preeclampsia.
AB  - OBJECTIVE: The aim of the study was to investigate the role of malondialdehyde,
      nitric oxide and adrenomedullin in the etiopathogenesis of preeclampsia. MATERIAL
      AND METHODS: Forty-two pregnant women with preeclampsia and 30 healthy pregnant
      women were involved. The plasma concentrations of malondialdehyde, nitric oxide,
      and adrenomedullin were compared between the study group and the control group.
      RESULTS: In women with preeclampsia the plasma concentrations of malondialdehyde
      was higher while nitric oxide and adrenomedullin concentrations were lower
      compared to control subjects. CONCLUSION: We concluded that the plasma levels of
      ADM and NO are decreased while MDA levels are increased in subjects with
      preeclampsia and that might contribute to the pathophysiology of preeclampsia
      through the lack of a paracrine vasodilatory effect on uteroplacental blood flow.

PMID- 19843002
TI  - Ca-ATPase activity of human red cell ghosts: preeclampsia, lipid peroxidation and
      MgSO4.
AB  - The increased level of lipid peroxidation of red blood cells during preeclampsia
      is considered to be responsible for the diminished Ca-ATPase activity in these
      cells. The level of lipid peroxidation and the Ca-ATPase activity of red blood
      cells from preeclamptic women, return to their normal values after in vivo and in
      vitro treatment with MgSO4 for 24 h. In order to evaluate whether or not cell
      intactness is essential for these changes, we used either intact red blood cells
      or red cell ghosts from normotensive pregnant women. The intact red blood cells
      were treated with Fenton's reagent and then incubated with 4 mM MgSO4. The red
      cells ghosts were irradiated with UV light and afterwards incubated with MgSO4 at
      4 degrees C. Lipid peroxidation and Ca-ATPase activity were determined for all
      the preparations. Both, Fenton's reagent and UV irradiation increased the level
      of lipid peroxidation and diminished the Ca-ATPase activity of the red cell
      membranes. Incubation of the cells treated with Fenton's reagent, or the ghosts
      irradiated with UV, with 4 mM MgSO4, returned Ca-ATPase activity and lipid
      peroxidation levels to normal values. The presence of MgSO4 blocked the effects
      in the ghosts of UV irradiation. MgSO4 seems to better protect the red cell
      membrane against lipid peroxidation than other SO4= and Cl- salts. These results
      indicate that the changes in the lipid peroxidation of the red cell ghosts and
      their Ca-ATPase activity are a result of changes to the cell membranes.

PMID- 19843003
TI  - Increased alpha-1 adrenoceptor expression in pregnant rats with subrenal aortic
      coarctation.
AB  - The progression of pregnancy is associated with attenuation in vasopressor
      response to adrenergic agonists. In pregnancy-induced hypertension this
      attenuation is reverted. It is not known if this reversion involves alpha-1
      adrenoceptor expression. OBJECTIVE: In this work we propose that in pregnant rats
      with subrenal aortic coarctation there are changes in the expression of alpha-1
      adrenergic receptors in the thoracic and abdominal aorta during pregnancy.
      METHODS: We used non-pregnant, normal pregnant and pregnant with subrenal aortic
      coarctation female Wistar rats. Pregnancy-induced hypertension indicators,
      systolic blood pressure, 24 hours proteinuria, pup weight and maternal weight
      were measured. Dose response curves to phenylephrine were carried out to
      determine vascular reactivity along pregnancy. Alpha 1-adrenoceptors were
      detected from thoracic and abdominal aorta using immunoblot. RESULTS: Results
      show significant increases in arterial pressure and proteinuria in pregnant rats
      with SRAC at the end of the third week. Pregnancy reduces alpha-(1-A, -B) and (
      D) adrenoceptor expression and this event is reverted by subrenal aortic
      coarctation. This phenomenon is more apparent in the abdominal segment of the
      aorta. CONCLUSIONS: These findings suggest that subrenal aortic coarctation is a
      good animal model of pregnancy-induced hypertension and that alpha1-adrenoceptors
      participate in its physiopathology increasing their expression in a segment
      dependent manner.

PMID- 19843004
TI  - A meta-analysis on the efficacy and safety of combined vitamin C and E
      supplementation in preeclamptic women.
AB  - OBJECTIVE: To evaluate whether vitamin C and E co-supplementation of women at
      risk of preeclampsia can reduce maternal and neonatal disorders. METHOD:
      Electronic databases were searched up to May 2008 to find studies investigating
      pregnancy outcomes in women at risk of preeclampsia following exposure to
      combined vitamin C and E supplementation. The outcomes of interest were
      gestational hypertension, preeclampsia, preterm delivery, small for gestational
      age, and low birth weight. The relative risk (RR) and confidence interval (CI)
      for the individual studies were pooled and heterogeneity analysis was performed.
      RESULTS: Seven studies involving 5969 pregnant women at risk of preeclampsia were
      included: 2982 received vitamin C and E and 2987 received placebo. The RRs are
      1.3 (95% CI of 1.08-1.57, p = 0.0066) for gestational hypertension, 0.7 (95% CI
      of 0.58-1.08, P = 0.1653) for preeclampsia, 1.12 (95% CI of 0.96-1.32, p = 0.141)
      for preterm delivery, 1.04 (95% CI of 0.94-1.15, p = 0.4789) for small for
      gestational age, and 1.13 (95% CI of 1.004-1.27, p = 0.0429) for low birth
      weight. CONCLUSION. Combined vitamin C and E supplementation not only have no
      potential benefit in improvement of maternal and neonatal outcome but increase
      the risk of gestational hypertension in women at risk of preeclampsia and low
      birth weight in neonates.

PMID- 19843005
TI  - Preeclampsia and risk of developing subsequent diabetes.
AB  - OBJECTIVE: Determine whether preeclampsia is associated with developing diabetes.
      METHODS: Subsequent diabetes was ascertained using ICD-9 codes, pharmacy and
      glucose data in a retrospective cohort study of 2,032 women with preeclampsia and
      29,431 without preeclampsia. RESULTS: During a median follow-up of 8.2 years, 342
      women developed diabetes. Preeclampsia was associated with a higher risk of
      diabetes adjusting for age, primigravidity, and gestational diabetes (hazard
      ratio, HR 1.82, 95%CI 1.26, 2.62) and in women without gestational diabetes (n =
      30,109; HR 1.86, 95%CI 1.22, 2.84). CONCLUSION: Women with preeclampsia have
      greater risk of developing diabetes, even in the absence of gestational diabetes.

PMID- 19843006
TI  - Exogenous soluble VEGF receptor-1 (sFlt-1) regulates Th1/Th2 cytokine production
      from normal placental explants via intracellular calcium.
AB  - OBJECTIVE: The increase of soluble VEGF-Receptor 1 (sFlt-1) is thought to
      contribute to the pathogenesis of preeclampsia. Soluble VEGF-Receptor 1 binds to
      circulating free VEGF and PLGF and this cascade is associated with endothelial
      dysfunction, a prominent feature of preeclampsia. Preeclampsia is also associated
      with excessive maternal response to pro-inflammatory stimuli manifesting as an
      imbalance of Th1/Th2 cytokine production at the maternal-fetal interface. Whether
      increased sFlt-1 expression has any effect on placental production of Th1/Th2
      cytokines IL-10 and TNF-alpha is yet to be investigated. The aim of this study is
      to examine if exogenous sFlt-1 can regulate Th1/Th2 cytokines IL-10 and TNF-alpha
      production from normal placental explants via intracellular calcium release.
      METHODS: Placental explants were taken from the decidual surface of normal non
      laboured term placentas (n = 11).Villous explants were cultured with increasing
      concentrations of sFlt-1. The dose effect of sFlt-1 on placental Th1 and Th2
      cytokine production (TNF-alpha and IL-10) were examined. Free PLGF, VEGF and sFlt
      1 concentrations in the conditioned medium were also measured. Intracellular
      calcium blocker, 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid,
      tetra(acetoxymethyl)-ester (BAPTA/AM) was applied to investigate whether the
      changes in cytokine concentration were mediated by intracellular free calcium.
      RESULTS: Placental IL-10 and TNF-alpha production were significantly increased
      after sFlt-1 incubation. The increase in IL-10 can be inhibited by BAPTA/AM.
      Soluble Flt-1 and free PLGF concentration in the conditioned medium was not
      changed. Free VEGF concentration in the conditioned medium was not detectable.
      CONCLUSION: Exogenous sFlt-1 can increase TNF-alpha and IL-10 production from
      normal placental explants. The change in Th1/Th2 cytokine level may be mediated
      by intracellular free calcium.

PMID- 19843007
TI  - Hypoxia upregulates GCM1 in human placenta explants.
AB  - Studies in mice have shown that a variety of genes, including GCM1, regulate the
      differentiation of trophoblast cells. GCM1 is also expressed in the human
      placenta. Placental GCM1 protein has been reported to be reduced in preeclampsia.
      In view of the close link between hypoxia, hypoxia-reoxygenation, preeclampsia,
      placental development and the reported reduction in GCM1, we hypothesised that
      GCM1 expression would be affected by hypoxia. The aim was to determine the
      effects of hypoxia on GCM1 expression in the human placenta. Two model systems
      were used; villous explants and cultured primary cytotrophoblast cells. GCM1
      protein was detectable at low levels in explants maintained for 7 h in 8 or 20%
      O2. A striking increase in GCM1 was observed when villous explants were incubated
      for 1h in 1% O2 (p < 0.002). Incubation of explants for 1 h in 1% O(2) followed
      by re-oxygenation for 6 h in 8 or 20% O2 resulted in a decline in GCM1 protein.
      Expression of GCM1 was also analysed in primary cytotrophoblast and
      syncytiotrophoblast cultured in 8 or 20% O2 or reduced oxygen (1-2% O2)
      conditions. GCM1 protein was not detected in any of the experimental conditions
      used. This study has shown that acute hypoxia increases GCM-1 protein in villous
      explants. The experiments with purified trophoblast do not support a role for
      hypoxia increasing GCM-1 in these cells under the conditions used. The present
      findings are in keeping with the complex effects of oxygen depending on the
      conditions used. The hypoxic effects on GCM1 warrant further investigation as
      they may provide further information on the pathogenesis of preeclampsia.

PMID- 19843008
TI  - Obesity and the hypertensive disorders of pregnancy.
AB  - Overweight and obesity have a strong association with the development of
      hypertensive disorders of pregnancy. However, the mechanisms underpinning this
      relationship are not clear. Obesity is associated with insulin resistance,
      endothelial dysfunction, hypertension dyslipidaemia, inflammatory upregulation,
      alteration in immune function and prothrombotic changes. These changes may
      contribute to the development of hypertensive disorders of pregnancy, by
      influencing placentation, endothelial function, and inflammation. The genetic
      predisposition for hypertensive disorders of pregnancy needs to be examined in
      the context of obesity. Common antecedents such as dietary factors and inadequate
      physical activity might also explain the relationship between hypertensive
      disorders of pregnancy and obesity. This review is concluded with a synopsis and
      recommendations for further research.

PMID- 19843010
TI  - Altered hippocampal morphology in unmedicated patients with major depressive
      illness.
AB  - Despite converging evidence that major depressive illness is associated with both
      memory impairment and hippocampal pathology, findings vary widely across studies
      and it is not known whether these changes are regionally specific. In the present
      study we acquired brain MRIs (magnetic resonance images) from 31 unmedicated
      patients with MDD (major depressive disorder; mean age 39.2+/-11.9 years; 77%
      female) and 31 demographically comparable controls. Three-dimensional parametric
      mesh models were created to examine localized alterations of hippocampal
      morphology. Although global volumes did not differ between groups, statistical
      mapping results revealed that in MDD patients, more severe depressive symptoms
      were associated with greater left hippocampal atrophy, particularly in CA1 (cornu
      ammonis 1) subfields and the subiculum. However, previous treatment with atypical
      antipsychotics was associated with a trend towards larger left hippocampal
      volume. Our findings suggest effects of illness severity on hippocampal size, as
      well as a possible effect of past history of atypical antipsychotic treatment,
      which may reflect prolonged neuroprotective effects. This possibility awaits
      confirmation in longitudinal studies.

PMID- 19843012
TI  - Intersection of the tocopherol and plastoquinol metabolic pathways at the
      plastoglobule.
AB  - Plastoglobules, lipid-protein bodies in the stroma of plant chloroplasts, are
      enriched in non-polar lipids, in particular prenyl quinols. In the present study
      we show that, in addition to the thylakoids, plastoglobules also contain a
      considerable proportion of the plastidial PQ-9 (plastoquinol-9), the redox
      component of photosystem II, and of the cyclized product of PQ-9, PC-8
      (plastochromanol-8), a tocochromanol with a structure similar to gamma-tocopherol
      and gamma-tocotrienol, but with a C-40 prenyl side chain. PC-8 formation was
      abolished in the Arabidopsis thaliana tocopherol cyclase mutant vte1, but
      accumulated in VTE1-overexpressing plants, in agreement with a role of tocopherol
      cyclase (VTE1) in PC-8 synthesis. VTE1 overexpression resulted in the
      proliferation of the number of plastoglobules which occurred in the form of
      clusters in the transgenic lines. Simultaneous overexpression of VTE1 and of the
      methyltransferase VTE4 resulted in the accumulation of a compound tentatively
      identified as 5-methyl-PC-8, the methylated form of PC-8. The results of the
      present study suggest that the existence of a plastoglobular pool of PQ-9, along
      with the partial conversion of PQ-9 into PC-8, might represent a mechanism for
      the regulation of the antioxidant content in thylakoids and of the PQ-9 pool that
      is available for photosynthesis.

PMID- 19843013
TI  - Oncocytic lesions of the ophthalmic region: a clinicopathological study with
      emphasis on cytokeratin expression.
AB  - PURPOSE: This study aimed to make a nationwide clinicopathological study of
      oncocytic lesions in the ophthalmic region and to characterize their cytokeratin
      (CK) expression. METHODS: All histologically diagnosed oncocytic lesions in the
      ophthalmic region registered in Denmark over a 25-year period were collected and
      re-evaluated using a monoclonal antimitochondrial antibody (MU213-UC). Clinical
      data were registered. Immunohistochemical characterization was performed with a
      panel of anti-CK antibodies. RESULTS: A total of 34 oncocytic lesions were
      identified and reviewed. The incidence that required surgical intervention in the
      Danish population could be approximated to 0.3 lesions per million capita per
      year. Patient ages ranged from 45 years to 89 years, with a peak incidence in the
      eighth decade. Female patients were twice as common as male. Lesions were
      typically described as red-brown, cystic and slow-growing. The antimitochondrial
      antibody MU213-UC produced a distinct and intense immunostaining of all oncocytic
      lesions and was found to be useful in substantiating oncocytic differentiation.
      Twenty-six of the lesions originated in the caruncle, three in the conjunctiva,
      two in the lacrimal sac, one at the semilunar plica, one on the eyelid margin and
      one peripunctally. Lesions were histologically classified as adenoma (oncocytoma)
      (26), hyperplasia (4) and metaplasia (4). Fourteen oncocytic lesions representing
      different locations and differentiation were further evaluated for CK expression.
      Basal-type oncocytic cells reacted with antibodies against CK 5 / 6, CK 7, CK 8,
      CK 13, CK 14, CK 17, CK 18 and CK 19, and suprabasal cells with CK 4, CK 7, CK 8,
      CK 18 and CK 19. Antibodies against CK 1+10 and CK 20 showed no reaction.
      CONCLUSIONS: Oncocytic lesions of the ophthalmic region most frequently present
      as caruncular oncocytomas. The CK profile is similar to the lacrimal- and
      accessory lacrimal gland duct elements and supports the theory that these lesions
      originate in the lacrimal- and accessory lacrimal glands.

PMID- 19843011
TI  - Role of phosphoinositides in STIM1 dynamics and store-operated calcium entry.
AB  - Ca2+ entry through store-operated Ca2+ channels involves the interaction at ER-PM
      (endoplasmic reticulum-plasma membrane) junctions of STIM (stromal interaction
      molecule) and Orai. STIM proteins are sensors of the luminal ER Ca2+
      concentration and, following depletion of ER Ca2+, they oligomerize and
      translocate to ER-PM junctions where they form STIM puncta. Direct binding to
      Orai proteins activates their Ca2+ channel function. It has been suggested that
      an additional interaction of the C-terminal polybasic domain of STIM1 with PM
      phosphoinositides could contribute to STIM1 puncta formation prior to binding to
      Orai. In the present study, we investigated the role of phosphoinositides in the
      formation of STIM1 puncta and SOCE (store-operated Ca2+ entry) in response to
      store depletion. Treatment of HeLa cells with inhibitors of PI3K
      (phosphatidylinositol 3-kinase) and PI4K (phosphatidylinositol 4-kinase)
      (wortmannin and LY294002) partially inhibited formation of STIM1 puncta.
      Additional rapid depletion of PtdIns(4,5)P2 resulted in more substantial
      inhibition of the translocation of STIM1-EYFP (enhanced yellow fluorescent
      protein) into puncta. The inhibition was extensive at a concentration of LY294002
      (50 microM) that should primarily inhibit PI3K, consistent with a major role for
      PtdIns(4,5)P2 and PtdIns(3,4,5)P3 in puncta formation. Depletion of
      phosphoinositides also inhibited SOCE based on measurement of the rise in
      intracellular Ca2+ concentration after store depletion. Overexpression of Orai1
      resulted in a recovery of translocation of STMI1 into puncta following
      phosphoinositide depletion and, under these conditions, SOCE was increased to
      above control levels. These observations support the idea that phosphoinositides
      are not essential but contribute to STIM1 accumulation at ER-PM junctions with a
      second translocation mechanism involving direct STIM1-Orai interactions.

PMID- 19843015
TI  - Macular hole closure following intravitreal triamcinolone injection in a
      previously vitrectomized diabetic eye.

PMID- 19843014
TI  - Refractive errors in children and young adults with Down's syndrome.
AB  - PURPOSE: Down's syndrome (DS) is the most common chromosomal anomaly. Numerous
      ophthalmic features have been reported. The aim of our study was to investigate
      the incidence of refractive errors in children and young adults with DS in
      Macedonia. METHODS: Fifty-six children and young adults with DS, aged 2-28 years,
      from Macedonia, underwent slit-lamp examination, ocular motility and refraction.
      RESULTS: The overall incidence of refractive errors in the Macedonian children
      and young adults with DS was 96.4%. A total of 17.8% of the subjects had myopia,
      23.2% had hypermetropia and 55.3% had astigmatism. Strabismus was seen in 13
      (23.2%) of the subjects (nine had esotropia, three had exotropia, one had
      hypertropia). CONCLUSIONS: The incidence of refractive errors in Macedonian
      children and young adults with DS was similar to that in Asian children. Compared
      with White (Caucasian) and Asian children with DS, Macedonian children and young
      adults exhibited lower incidences of hypermetropia and myopia, and a higher
      incidence of astigmatism, in which oblique astigmatism represented the
      predominant type.

PMID- 19843016
TI  - Reactivity of white blood cell flux to hyperoxia in patients infected with human
      immunodeficiency virus.
AB  - PURPOSE: The aetiology of the apparently vasoocclusive phenomena in human
      immunodeficiency virus (HIV)-related retinopathy is not well understood. Several
      hypotheses, including infectious damage of the retinal vasculature and altered
      retinal haemodynamics, have been postulated. Direct measurement of oxygen tension
      in the retina is not possible in vivo and indirect methods have to be employed.
      The objective of this study was to investigate the retinal vascular response to
      100% oxygen breathing in patients with HIV. METHODS: Twelve patients infected
      with HIV and 12 healthy individuals, matched for age, sex and smoking habits,
      were studied in an open study using the blue-field entoptic technique for the
      measurement of retinal white blood cell (WBC) flux. Reactivity in retinal blood
      flow during 100% O(2) breathing over 15 min was measured and expressed as
      percentage change over baseline. RESULTS: WBC velocity during oxygen inhalation
      decreased over baseline by 9.0 +/- 5.8% in HIV-infected patients and by 18.6 +/-
      5.4% in healthy participants (p < 0.04 between groups, ANOVA). The decrease in
      WBC velocity was paralleled by a decrease in WBC density. This decrease tended to
      be more pronounced in healthy participants (13.6 +/- 7.9%) than in HIV-infected
      patients (8.0 +/- 10.8%), but the difference was not statistically significant (p
      = 0.1 between groups, ANOVA). WBC flux decrease was 16.2 +/- 11.4% in HIV
      infected patients and 29.5 +/- 9.5% in the control group and was significant
      between groups (p = 0.007 between groups, ANOVA). CONCLUSION: Our results
      indicate a reduced reactivity of WBC flux to systemic hyperoxia in patients with
      HIV. Whether abnormal retinal haemodynamics in HIV-infected persons contributes
      to the pathogenesis of HIV-related microvascular diseases or is a consequence of
      the structural changes associated with the disease is unknown.

PMID- 19843017
TI  - Stable refraction and visual acuity in diabetic patients with variable glucose
      levels under routine care.
AB  - PURPOSE: To investigate how refraction and visual acuity may vary in patients
      with diabetes under routine care. METHODS: Fifty-three eyes of 53 patients with
      various degrees of diabetic retinopathy were examined prospectively on four
      different occasions within a month. Refraction, best-corrected visual acuity
      (expressed as logMAR score) and blood glucose were measured on each occasion.
      Intraindividual variability was calculated as the range between the highest and
      lowest measurements. Associations between blood glucose levels and each of the
      other variables were tested by linear regression analysis for each patient.
      RESULTS: Refraction was completely stable in 43 patients and changed only
      slightly in 10, in whom the mean intraindividual variability of the spherical
      equivalent was 0.4 dioptres. Visual acuity test results were also highly
      reproducible. Mean intraindividual variability in visual acuity was 0.08 logMAR.
      Mean haemoglobin A1c (HbA1c) was 7.3 +/- 1.5% but individual blood glucose levels
      ranged from 2.8 to > 22.2 mmol/l. Intraindividual variability ranged from 0.5 to
      18.1 mmol/l, with a median of 6.0 mmol/l for the entire group. There were no
      associations between refraction or visual acuity and blood glucose levels or
      inter- or intraindividual glucose variations. CONCLUSION:   Refraction and visual
      acuity test results were highly reproducible and stable in patients with
      reasonably well controlled diabetes but variable blood glucose levels under
      routine care.

PMID- 19843018
TI  - Limitations of relaxation kinetics on muscular work.
AB  - AIM: Positive net work produced during cyclic contractions is partially limited
      by relaxation kinetics, which to date, have not been directly investigated.
      Therefore, the purpose of this investigation was to determine the influence of
      relaxation kinetics on cyclic work. METHODS: Soleus muscles of four cats were
      isolated and subjected to a series of work loops (0.5, 1, 1.5 and 2 Hz cycle
      frequencies) during which stimulation terminated prior to the end of the
      shortening phase to allow for complete muscle relaxation and matched discrete
      sinusoidal shortening contractions during which stimulation remained on until the
      completion of the shortening phase. Muscle length changes during these protocols
      were centred on optimum length and were performed across muscle lengths that
      represented walking gait. RESULTS: When muscle excursions were centred on L(o)
      relaxation kinetics decreased muscular work by 2.8 + or - 0.8%, 12.1 + or - 4.1%,
      27.9 + or - 4.5% and 40.1 + or - 5.9% for 0.5, 1, 1.5 and 2 Hz respectively.
      However, relaxation kinetics did not influence muscular work when muscle
      excursions represented walking gait. In addition, muscular work produced at
      muscle lengths associated with walking gait was less than the work produced
      across L(o) (55.7 + or - 20.0%, 53.5 + or - 21.0%, and 50.1 + or - 22.0% for 0.5,
      1 and 1.5 Hz respectively). CONCLUSION: These results imply that relaxation
      kinetics are an important factor that limit the ability of muscle to produce
      work; however, the influence of relaxation kinetics on physiological function may
      depend on the relation between the optimum length and natural excursion of a
      muscle.

PMID- 19843019
TI  - Unusual aetiology for supraumbilical abdominal pain in school-age patient (Case
      Presentation).

PMID- 19843020
TI  - Chest pain in a 15-year-old girl (Case Presentation).

PMID- 19843021
TI  - Is autism reversible?

PMID- 19843022
TI  - Neuroprotein s-100B -- a useful parameter in paediatric patients with mild
      traumatic brain injury?
AB  - AIMS: To examine the correlation of S-100B to cranial computerized tomography
      (CCT) scan results in children after mild traumatic brain injury (MTBI). METHODS:
      One hundred and nine paediatric patients (0-18 years) with MTBI were included in
      this prospective single-centre study. Serum was collected within 6 h of trauma
      for determination of serum S-100B. The upper reference of S-100B was set to 0.16
      mug/L. A CCT scan was performed in all patients and the results were correlated
      to the S-100B values. RESULTS: Computerized tomography was abnormal in 36
      patients showing intracerebral haemorrhages and/or skull fractures. Serum S-100B
      level was significantly higher in patients with a pathological condition as shown
      in CT scan results (p = 0.003). There were no false negative, but 42 false
      positive test results for S-100B. This resulted in a sensitivity of 1.00,
      specificity of 0.42, positive predictive value of 0.46 and negative predictive
      value of 1.00. An area under the receiver operating curve of 0.68 was calculated.
      CONCLUSION: S-100B is a valuable tool to rule out patients with pathological CCT
      findings in a collective of paediatric patients with MTBI. Elevations of S-100B
      do not necessarily lead to a pathological finding in the CT scan, but values
      below the cut-off safely rule out the evidence of intracranial lesions.

PMID- 19843025
TI  - Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and
      oesophageal adenocarcinoma.
AB  - BACKGROUND: Accumulating evidence suggests that cyclooxygenase-2 (COX-2)-derived
      prostaglandin E2 (PGE2) is involved in oesophageal adenocarcinogenesis. PGE2
      exerts its biological action by binding to specific receptors (EP1, EP2, EP3 and
      EP4). AIM: To investigate which PGE2 receptor subtypes regulate PGE2 signals in
      the oesophageal adenocarcinoma sequence. METHODS: Expression was determined in
      oesophageal biopsies from 85 patients with oesophagitis, Barrett's metaplasia,
      intraepithelial neoplasia, oesophageal adenocarcinoma and normal oesophagus.
      Levels of mRNA and protein expression were determined by quantitative PCR,
      immunohistochemistry and western-blot. Expression of EP receptors was also
      determined in response to acid and bile exposure in the Barrett's adenocarcinoma
      cell line OE33. RESULTS: All four EP receptors subtypes were expressed in human
      oesophageal tissues. COX-2 and, especially, EP2 were increased in the Barrett's
      metaplasia-intraepithelial neoplasia-adenocarcinoma sequence. Expression of the
      EP4 receptor protein was increased in oesophageal adenocarcinoma. In contrast,
      expression levels of COX-1 and EP3 receptor were decreased along the sequence. No
      differences in EP1 expression were found. Treatment with the bile acid
      deoxycholate increased COX-2, EP1, EP2 and EP4 expression in OE33 cells.
      CONCLUSIONS: Our data suggest that in addition to COX-2, EP2 and EP4 receptors
      could be a selective target in the prevention and/or treatment of the Barrett's
      associated adenocarcinoma.

PMID- 19843026
TI  - The AJT report: News and issues that affect organ and tissue transplantation.
      Belatacept results promising...with some caveats.

PMID- 19843027
TI  - The 'indirect' effects of cytomegalovirus infection.
AB  - Cytomegalovirus (CMV) remains the most important infection in the
      immunocompromized host even in the era of effective therapy. CMV is usually
      acquired early in life and can be transmitted by contact with infected body
      fluids. In the immunocompetent population, primary infection is almost always of
      little clinical consequence. However, CMV infection in immunocompromized
      patients, especially those naive to CMV exposure, can cause tissue invasive
      disease, severe symptoms and/or death. However, beyond these direct effects,
      increasing in vitro evidence is accumulating that suggests CMV has many other
      effects on the host's immune response which may explain some of the detrimental
      consequences for the immunosuppressed patient, and may also be partially
      responsible for a variety of conditions in immunocompetent individuals. In its
      latent state, CMV employs several mechanisms to evade detection by the host's
      immune system. The virus also employs other methods to take advantage of
      activation of the immune system and replicate in sites of inflammation. This
      review focuses on the immunosuppressive and inflammatory mechanisms that have
      been attributed to CMV and will relate them to some of the clinical sequellae
      that have been associated with the indirect effects of CMV infection.

PMID- 19843028
TI  - The Declaration of Istanbul: review and commentary by the American Society of
      Transplant Surgeons Ethics Committee and Executive Committee.
AB  - The American Society of Transplant Surgeons (ASTS) was asked to endorse the 'The
      Declaration of Istanbul on Organ Trafficking and Transplant Tourism.' The
      document has been reviewed by the ASTS Ethics Committee and their ensuing report
      was presented, discussed and approved by the ASTS Council. The ASTS vigorously
      supports the principles outlined in the Declaration and details specific current
      obstacles to implementation of some of its proposals in the United States.

PMID- 19843029
TI  - Viral infection induces de novo lesions of coronary allograft vasculopathy
      through a natural killer cell-dependent pathway.
AB  - Viral infections including those due to cytomegalovirus have been associated with
      accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some
      animal models. Evidence demonstrating a direct causal relationship between such
      infections and de novo formation of coronary vascular lesions is lacking.
      Heterotopic murine cardiac transplants were performed in a parental to F1
      combination in animals lacking both T- and B-lymphocytes (RAG(-/-)). Coronary
      vasculopathy developed almost exclusively in the presence of recipient infection
      with lymphocytic choriomeningitis virus but not in uninfected controls. This
      process was also dependent upon the presence of natural killer (NK) cells as
      depletion of NK cells abrogated the process. These data show that a viral
      infection in its native host, and not previously implicated in the production of
      CAV, can contribute to the development of advanced coronary vascular lesions in
      cardiac allotransplants in mice. These data also suggest that virus-induced CAV
      can develop via an NK-cell-dependent pathway in the absence of T- and B
      lymphocytes.

PMID- 19843030
TI  - Antibody-mediated microcirculation injury is the major cause of late kidney
      transplant failure.
AB  - We studied the phenotype of late kidney graft failure in a prospective study of
      unselected kidney transplant biopsies taken for clinical indications. We analyzed
      histopathology, HLA antibodies and death-censored graft survival in 234
      consecutive biopsies from 173 patients, taken 6 days to 31 years posttransplant.
      Patients with late biopsies (>1 year) frequently displayed donor-specific HLA
      antibody (particularly class II) and microcirculation changes, including
      glomerulitis, glomerulopathy, capillaritis, capillary multilayering and C4d
      staining. Grafts biopsied early rarely failed (1/68), whereas grafts biopsied
      late often progressed to failure (27/105) within 3 years. T-cell-mediated
      rejection and its lesions were not associated with an increased risk of failure
      after biopsy. In multivariable analysis, graft failure correlated with
      microcirculation inflammation and scarring, but C4d staining was not significant.
      When microcirculation changes and HLA antibody were used to define antibody
      mediated rejection, 17/27 (63%) of late kidney failures after biopsy were
      attributable to antibody-mediated rejection, but many were C4d negative and
      missed by current diagnostic criteria. Glomerulonephritis accounted for 6/27 late
      losses, whereas T-cell-mediated rejection, drug toxicity and unexplained scarring
      were uncommon. The major cause of late kidney transplant failure is antibody
      mediated microcirculation injury, but detection of this phenotype requires new
      diagnostic criteria.

PMID- 19843031
TI  - De novo donor-specific antibody at the time of kidney transplant biopsy
      associates with microvascular pathology and late graft failure.
AB  - We studied whether de novo donor-specific antibodies (DSA) in sera from patients
      undergoing kidney transplant biopsies associate with specific histologic lesions
      in the biopsy and prognosis. DSA were assessed in 145 patients at the time of
      biopsy between 7 days to 31 years posttransplant. DSA was detected in 54 patients
      (37%), of which 32 represented de novo DSA. De novo DSA was more frequent in
      patients having late biopsies (34%) versus early biopsies (4%), and was usually
      either against class II alone or class I and II but rarely against class I alone.
      Microcirculation inflammation (glomerulitis, capillaritis) and damage
      (glomuerulopathy, capillary basement membrane multilayering), and C4d staining
      were associated with de novo DSA. However, the degree of scarring, arterial
      fibrosis and tubulo-interstitial inflammation did not correlate with the presence
      of de novo DSA. De novo DSA correlated with reduced graft survival after the
      biopsy. Thus, de novo DSA at the time of a late biopsy for clinical indication is
      primarily against class II, and associates with microcirculation changes in the
      biopsy and subsequent graft failure. We propose careful assessment of de novo
      DSA, particularly against class II, be performed in all late kidney transplant
      biopsies.

PMID- 19843032
TI  - Donor-estimated GFR as an appropriate criterion for allocation of ECD kidneys
      into single or dual kidney transplantation.
AB  - It has been suggested that dual kidney transplantation (DKT) improves outcomes
      for expanded criteria donor (ECD) kidneys. However, no criteria for allocation to
      single or dual transplantation have been assessed prospectively. The strategy of
      DKT remains underused and potentially eligible kidneys are frequently discarded.
      We prospectively compared 81 DKT and 70 single kidney transplant (SKT) receiving
      grafts from ECD donors aged >65 years, allocated according to donor estimated
      glomerular filtration rate (eGFR): DKT if eGFR between 30 and 60 mL/min, SKT if
      eGFR greater than 60 mL/min. Patient and graft survival were similar in the two
      groups. In the DKT group, 13/81 patients lost one of their two kidneys due to
      hemorrhage, arterial or venous thrombosis. Mean eGFR at month 12 was similar in
      the DKT and SKT groups (47.8 mL/min and 46.4 mL/min, respectively). Simulated
      allocation of kidneys according to criteria based on day 0 donor parameters such
      as those described by Remuzzi et al., Andres et al. and UNOS, did not indicate an
      improvement in 12-month eGFR compared to our allocation based on donor eGFR.

PMID- 19843033
TI  - Interstitial fibrosis quantification in renal transplant recipients randomized to
      continue cyclosporine or convert to sirolimus.
AB  - Conversion from cyclosporine (CsA) to sirolimus at week 12 after kidney
      transplantation is associated with a significant improvement in renal function.
      The aim of this analysis was to investigate the effect of this conversion on
      interstitial fibrosis (IF), a hallmark of chronic allograft injury, in patients
      taking part in the CONCEPT trial. This multicenter, prospective, trial included
      193 renal recipients randomized at week 12 to switch from CsA to sirolimus or to
      continue CsA, with mycophenolate mofetil. Routine biopsy with automated,
      quantified assessment of IF by a program of color segmentation was performed at 1
      year in 121 patients. At 1 year, renal function was significantly improved in the
      conversion group as assessed by estimated GFR (MDRD) and measured GFR. Biopsy
      results, however, showed no between-group difference in percentage of IF.
      Calculated GFR at 1 year was significantly associated with the percentage of IF
      (p = 0.004, R(2)= 0.07). By multivariate analysis diabetic patients had more
      fibrosis than non-diabetic patients. In conclusion, although kidney transplant
      patients converted from CsA to sirolimus showed significant improvement in renal
      function, we found no difference of IF on 1-year biopsies.

PMID- 19843034
TI  - Strain-encoded cardiac magnetic resonance for the evaluation of chronic allograft
      vasculopathy in transplant recipients.
AB  - The aim of our study was to investigate the ability of Strain-Encoded magnetic
      resonance imaging (MRI) to detect cardiac allograft vasculopathy (CAV) in heart
      transplantation (HTx)-recipients. In consecutive subjects (n = 69), who underwent
      cardiac catheterization, MRI was performed for quantification of myocardial
      strain and perfusion reserve. Based on angiographic findings subjects were
      classified: group A including patients with normal vessels; group B, patients
      with stenosis <50%; and group C, patients with severe CAV (stenosis >or= 50%).
      Significant correlations were observed between myocardial perfusion reserve with
      peak systolic strain (r =-0.53, p < 0.001) and with mean diastolic strain rate (r
      = 0.82, p < 0.001). Peak systolic strain and strain rate were significantly
      reduced only in group C, while mean diastolic strain rate and myocardial
      perfusion reserve were already reduced in group B and A. Myocardial perfusion
      reserve and mean diastolic strain rate had higher accuracy for the detection of
      CAV (AUC = 0.95, 95% CI = 0.87-0.99 and AUC = 0.93, 95% CI = 0.84-0.98,
      respectively) and followed peak systolic strain and strain rate (AUC = 0.80, 95%
      CI = 0.69-0.89 and AUC = 0.78, 95% CI = 0.67-0.87, respectively). Besides the
      quantification of myocardial perfusion, the estimation of the diastolic strain
      rate is a useful parameter for CAV assessment. In combination with the clinical
      evaluation, these parameters may be effective tools for the routine surveillance
      of HTx-recipients.

PMID- 19843035
TI  - Transplant outcomes and economic costs associated with patient noncompliance to
      immunosuppression.
AB  - We describe factors associated with immunosuppression compliance after kidney
      transplantation and examine relationships between compliance with allograft
      outcomes and costs. Medicare claims for immunosuppression in 15 525 renal
      transplant recipients with at least 1 year of graft function were used to
      calculate compliance as medication possession ratio. Compliance was categorized
      by quartiles as poor, fair, good and excellent. We modeled adjusted associations
      of clinical factors with the likelihood of persistent compliance by multiple
      logistic regressions (aOR), and estimated associations of compliance with
      subsequent graft and patient survival with Cox proportional hazards (aHR).
      Adolescent recipients aged 19-24 years were more likely to be persistently
      noncompliant compared to patients aged 24-44 years (aOR 1.49 [1.06-2.10]). Poor
      (aHR 1.80 [1.52-2.13]) and fair (aHR 1.63[1.37-1.93]) compliant recipients were
      associated with increased risks of allograft loss compared to the excellent
      compliant recipients. Persistent low compliance was associated with a $12 840
      increase in individual 3-year medical costs. Immunosuppression medication
      possession ratios indicative of less than the highest quartile of compliance
      predicted increased risk of graft loss and elevated costs. These findings suggest
      that interventions to improve medication compliance among kidney transplant
      recipients should emphasize the benefits of maximal compliance, rather than
      discourage low compliance.

PMID- 19843036
TI  - HLA class I antibodies provoke graft arteriosclerosis in human arteries
      transplanted into SCID/beige mice.
AB  - Antibodies toward HLA class I and/or MICA are commonly observed in transplanted
      patients suffering from allograft arteriosclerosis, also called chronic vascular
      rejection (CVR). The relative importance of cellular versus humoral
      alloreactivity for CVR is still disputed. We demonstrate that antibodies toward
      HLA class I provoke lesions typical for CVR in human arteries in vivo in the
      absence of cellular immunity. To show this, we grafted segments of human
      mesenteric arteries from 8 deceased organ donors into 36 immunodeficient
      SCID/beige mice in the infrarenal aortic position. Three mice died
      postoperatively. The remaining 33 mice received weekly i.v. injections of either
      a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal
      antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a
      significant neointimal thickening in the grafted artery due to smooth muscle cell
      (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody
      showed little or no thickening. Whereas antibodies toward HLA class I were
      mitogenic to SMC in vitro, those directed toward MICA did not have any effect.
      Humoral alloreactivity toward HLA may thus play a causal role for the development
      of CVR and this opens new possibilities for the treatment of CVR.

PMID- 19843037
TI  - Regulatory allospecific NK cell function is differentially associated with HLA C
      allotypes.
AB  - Major histocompatibility complex I (MHC I) molecules 'silence' natural killer
      (NK) cell activity. Conversely, NK cell activity is triggered through cells
      lacking expression of autologous MHC I. Unexpectedly we found that a subset of NK
      cells is activated rather than silenced when interacting with cells expressing
      normal levels of autologous MHC I. Instead of inducing an inflammatory phenotype,
      however, activation led to the secretion of the regulatory cytokines TGF-beta and
      IL-10. Importantly, in vitro models of allogeneic interactions showed that
      targets co-expressing HLA C1 and C2 epitopes best supported, or even enhanced,
      this cell-contact-mediated regulatory NK cell function. Together, these data
      ascribe a novel pattern of reactivity to NK cells, with potential implications
      both in autologous and allogeneic systems.

PMID- 19843038
TI  - Strongyloides stercoralis hyperinfection transmitted by liver allograft in a
      transplant recipient.
AB  - We describe a case of Strongyloides stercoralis hyperinfection in a liver
      allograft recipient 2.5 months after transplantation. The patient lives in Spain,
      which is not considered an endemic country for strongyloidiasis, and denied prior
      residence or travel to any known endemic area. The initial symptoms were fever
      and vomiting, and he subsequently developed a severe respiratory disease. An
      endoscopic biopsy of ulcerative lesions of the duodenum revealed massive mucosa
      infiltration by larvae and adult worms, which were also found in respiratory
      samples. The patient was successfully treated with combined therapy with
      albendazole and ivermectin. The strongyloides infection was transmitted by the
      liver allograft. The donor was from Ecuador and, retrospectively, his serum
      tested positive for S. stercoralis IgG antibodies. Additionally, the pancreas
      left kidney allograft recipient from the same donor later developed an intestinal
      strongyloidiasis without hyperinfection syndrome. To our knowledge, this is the
      first confirmed case of S. stercoralis infection transmission from the same donor
      to two solid allograft recipients.

PMID- 19843043
TI  - Melatonin and vitamin C attenuates alcohol-induced oxidative stress in aorta.
AB  - Epidemiological studies have shown that low to moderate doses of alcohol
      consumption are beneficial to cardiac health. However, chronic high doses of
      alcohol ingestion cause cardiovascular complications. The aim of this study was
      to investigate both the effects of melatonin and vitamin C and expression of
      endothelial nitric oxide synthase in aorta of chronic alcoholic rats. Twenty-four
      adult male Wistar rats weighing 200-250 g were used in the study. Rats were
      divided into four equal groups. Group I (control): rats were not fed on alcohol;
      Group II: rats were fed on alcohol; Group III: rats were fed on alcohol and 40
      mg/kg vitamin C were injected intraperitoneally and Group IV: rats were fed on
      alcohol and 4 mg/kg melatonin were injected intraperitoneally. At the end of the
      experiment, rats were killed and aorta tissues were removed. Some parts of the
      aorta tissues were used for biochemical analyses and the other parts were used at
      histological procedures. In the control group, endothelial nitric oxide synthase
      immunoreactivity was (++) in smooth muscle cells and endothelial cells.
      Expression of endothelial nitric oxide synthase in the alcohol group was stronger
      than control group. Chronic ethanol ingestion significantly increased (p < 0.05);
      and melatonin significantly decreased both the plasma and tissue malondialdehyde
      levels. The superoxide dismutase levels and catalase activity did not change
      significantly in the Vitamin C and melatonin groups (p > 0.05) compared to the
      control and alcohol groups. The present results indicate that chronic alcohol
      consumption increase lipid peroxidation and cause endothelial nitric oxide
      synthase expression in the aorta. However, melatonin and vitamin C administration
      provide partial protection against alcohol-induced damage.

PMID- 19843044
TI  - Adolescents' beliefs about their parents' human papillomavirus vaccination
      decisions.
AB  - A significant minority of parents are concerned that human papillomavirus
      vaccination will affect sexual behaviour. We explored this issue with 162
      adolescent girls. Most (between 90 and 92%) did not perceive a connection between
      parental consent to vaccination and parental authorisation for sexual activity,
      but a small percentage believed that vaccination consent implied that they were
      old enough to have sex (8%), or that it was okay for them to be sexually active
      (10%). The findings are broadly reassuring, but highlight the need for
      vaccination information materials to clarify why the vaccine is administered
      before sexual debut.

PMID- 19843045
TI  - Disorders of ovarian function in childhood and adolescence: evolving needs of the
      growing child. An endocrine perspective.
AB  - Over the past 15 years there have been changes in the care of children and
      adolescents paralleling increased longevity of those with chronic illnesses and
      increased survival after childhood cancer and organ transplantation. A broad
      understanding of holistic management and long-term risks is required.
      Optimisation of pubertal progress and normalisation of bone and hormonal health
      by the end of puberty will reduce the impact of later adult bone loss in chronic
      disease conditions. Psychosocial issues related to both precocious and delayed
      puberty can have profound effects on family function.

PMID- 19843046
TI  - Service users' experiences of obtaining and giving information about disorders of
      sex development.
AB  - OBJECTIVE: To quantify participants' experiences of obtaining and giving
      information about disorders of sex development (DSD). DESIGN: Cross-sectional
      survey study that asked people about their current and past experiences relating
      to DSD disclosure. SETTING: A large tertiary referral centre for DSD management
      in the UK. POPULATION: One hundred of 126 people with a confirmed diagnosis of
      DSD who were invited to participate in the study formed the usable sample.
      METHODS: All people who attended clinic for follow-up during the study period and
      members of a patient support group whose annual meeting fell within the study
      period were asked to complete the Middlesex Communication Survey. MAIN OUTCOME
      MEASURES: The Middlesex Communication Survey. RESULTS: Younger participants were
      more likely to report having been appropriately informed about their diagnosis
      than older people. Nearly half of the former had been fully informed about their
      diagnosis by age 15 years, compared with 0% of the older age group. In terms of
      information sharing, mothers were most likely to be the person with whom the
      participant had shared (almost/all) DSD information (74%), followed by current
      partners (71%). Information relating to genital surgery, presence of testes and
      clitoral anomalies were the least likely aspects to have been unambiguously
      shared with even the most informed person. CONCLUSIONS: Our results suggest that
      difficulties in obtaining DSD information from care providers were common, and
      that communication has improved for younger participants. The study also
      confirmed that many people with DSD continue to struggle with confiding, even in
      those closest to them, about aspects of their diagnosis. Care protocol needs to
      centralise psychological adaptation, which should also be a primary focus for
      future research.

PMID- 19843047
TI  - Clinical networks in paediatric and adolescent gynaecology.

PMID- 19843048
TI  - Endothelial progenitor cells & translational research.

PMID- 19843049
TI  - Abatacept.

PMID- 19843050
TI  - Panitumumab.

PMID- 19843052
TI  - Proposals for model-based paediatric medicinal development within the current
      European Union regulatory framework.
AB  - The new paediatric European Union (EU) regulation and the consequent demand for
      paediatric studies on one hand and the ethical need for minimizing the burden of
      studies in children on the other hand necessitate optimal techniques in the
      assessment of safety/efficacy and use of drugs in children. Modelling and
      simulation (M&S) is one way to circumvent some difficulties in developing
      medicinal products in children. M&S allows the quantitative use of sparse
      sampling, characterization and prediction of pharmacokinetics/pharmacodynamics
      (PK/PD), extrapolation from adults to children, interpolation between paediatric
      age subsets, optimal use of scientific literature and in vitro/preclinical data.
      Together, industry, academia and regulators recognize the usefulness of modelling
      and simulation in this setting. However, even if M&S is an emerging science, its
      integration in the EU regulatory decision making is for the time being deficient
      and M&S expertise is concentrated in big pharmaceutical companies and academic
      institutions. The European Medicines Agency, acknowledging all the above
      conditions, organized and hosted a Workshop on Modelling in Paediatric Medicines.
      The article presents the personal views of the authors on the issues presented
      and discussed in the workshop.We attempt to identify the regulatory framework for
      the use of M&S in paediatric medicinal development and to make proposals for
      model-based paediatric medicinal development. The objective is to open the
      discussion between industry, academia, paediatricians and regulators on the
      optimal use of M&S in paediatric medicinal development.

PMID- 19843051
TI  - Progenitors in motion: mechanisms of mobilization of endothelial progenitor
      cells.
AB  - Endothelial progenitor cells are a population of bone marrow-derived mononuclear
      cells thought to engage in endothelial repair and hence are considered potential
      therapeutic agents in many pathological conditions. The mechanism of their exit
      from the bone marrow to the circulation and damaged tissues, termed mobilization,
      has not been fully elucidated. Despite this, several pharmacological
      interventions have been shown to influence mobilization of these specialized
      cells. Here we review the current understanding of their mobilization.

PMID- 19843053
TI  - Effect of the urotensin-II receptor antagonist palosuran on secretion of and
      sensitivity to insulin in patients with Type 2 diabetes mellitus.
AB  - AIMS: To investigate the effects of palosuran, a nonpeptidic, potent and
      selective antagonist of the urotensin-II receptor, on insulin and glucose
      regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double
      blind, placebo-controlled, randomized, crossover, proof-of-concept study.
      METHODS: After 4 weeks' oral treatment with 125 mg palosuran or placebo
      b.i.d.,effects on insulin secretion and sensitivity and blood glucose levels were
      assessed by means of a hyperglycaemic glucose clamp, meal tolerance test,
      homeostasis model assessment-insulin resistance score, and daily self-monitoring
      of blood glucose. Plasma concentrations of palosuran were determined for 12 h on
      the last day of intake. RESULTS: Palosuran did not affect second-phase insulin
      response (primary end-point) during the hyperglycaemic glucose clamp in
      comparison with placebo [paired difference of -1.8 microU ml(-1), 95% confidence
      interval (CI) -7.8, 4.2]. Likewise, no effects of palosuran were detected on the
      first-phase insulin response, or on insulin secretion and blood glucose levels
      during the meal tolerance test or on homeostasis model assessment-insulin
      resistance score. No clinically significant effects on daily blood glucose
      profiles were observed during the study. Geometric mean C(max) and AUC(tau) (95%
      CI) and median t(max) (range) in this patient population were 180 ng ml(-1) (125,
      260), 581 ng.h ml(-1) (422, 800) and 3.0 h (0.67, 4.3), respectively.
      CONCLUSIONS: The results of this study indicate that antagonism of the urotensin
      II system does not influence insulin secretion or sensitivity or daily blood
      glucose levels in diet-treated patients with Type 2 diabetes.

PMID- 19843054
TI  - A comparison of two formulations of intradermal capsaicin as models of
      neuropathic pain in healthy volunteers.
AB  - AIMS: To compare the dose-response relationships of two formulations [Tween- or
      hydroxypropyl-b-cyclodextrin (HP-b-CD)-based] of intradermal capsaicin in healthy
      volunteers and to assess the effect of potential covariates of response. One, 10,
      30 and 100 microg in 10 ml were compared for the outcomes of flare, spontaneous
      pain, mechanical allodynia and hyperalgesia in eight healthy men and eight
      healthy women. RESULTS: The formulations produced comparable responses at doses
      1, 10 and 30 microg, but in all parameters the response was less at 100 microg
      with the Tween formulation.Mean area for hyperalgesia was 9 cm(2) [95% confidence
      interval (CI) 5, 13] higher with the HP-beta-CD formulation. Flare area was 5
      cm(2) (95% CI 8, 13) greater with the HP-beta-CD formulation. There was a
      significant difference between pain responses from the injection site on the
      upper forearm compared with the lower forearm on all four pain assessments. In
      contrast, significant differences were seen in pain response between nondominant
      and dominant arm for flare, allodynia and hyperalgesia but not for spontaneous
      pain. A significant difference in sex was seen only for hyperalgesia. The nominal
      100-microg dose of the Tween formulation contained only 39% of label strength in
      the aqueous phase, which may explain the lower pharmacodynamic response.
      CONCLUSION: The formulations are comparable over the dose range 1-30 microg. The
      significantly lower pain response at the 100 microg dose in the Tween compared
      with the HP-beta-CD formulation is likely to be due to limitations in solubility
      at the 100 microg level. Given the greater ease of formulation and the superior
      dose-response relationship, the HP-beta-CD formulation is preferable for use in
      the model in future studies.

PMID- 19843055
TI  - The effects of urotensin II and urantide on forearm blood flow and systemic
      haemodynamics in humans.
AB  - AIMS: (i) To compare the effects of intra-arterial administration of urotensin II
      in patients with CVD with healthy volunteers, and (ii) to study the haemodynamic
      effects of intra-arterial infusion of the urotensin II receptor antagonist,
      urantide. METHODS: Ten healthy volunteers and 10 patients with CVD received a
      dose-ramped brachial artery infusion of urotensin II. A further six healthy male
      volunteers received a prolonged urotensin II infusion and 11 healthy male
      volunteers received a dose-ramped infusion of urantide. Forearm blood flow (FBF)
      was measured every 20 min and blood pressure and heart rate were assessed every
      20 min. RESULTS: In healthy volunteers and patients with CVD, intra-arterial
      infusion of urotensin II had no effect on FBF ratio. A dose-ramped infusion of
      urantide similarly had no effect on FBF ratio. During dose-ramped infusions of
      urotensin II and urantide, systolic and mean arterial blood pressure increased
      significantly. In healthy volunteers, urotensin II and urantide, respectively,
      increased systolic blood pressure from 133 +/- 6 to 137 +/- 5 mmHg (P < 0.01) and
      from 113 +/- 4 to 120 +/- 4 mmHg (P < 0.01). In patients with CVD, heart rate
      also significantly increased during dose-ramped infusion of urotensin II from 59
      +/- 3 to 62 +/- 4 bpm (P < 0.05). CONCLUSIONS: We have shown no in vivo effect of
      urotensin II or urantide on human forearm resistance vessels. Previous
      discrepancies do not seem to relate to either the age or CVD status of subjects.
      Changes in systemic cardiovascular haemodynamics during the dose-ramped infusion
      studies are unlikely to be caused by urotensin II receptor modulation.

PMID- 19843056
TI  - Central nervous system effects of alcohol at a pseudo-steady-state concentration
      using alcohol clamping in healthy volunteers.
AB  - AIM: In determining the acute effects of alcohol, it is helpful if alcohol
      concentrations are maintained at stable levels, to facilitate the interpretation
      of the results. Recently, an alcohol clamping method was developed that resulted
      in stable alcohol concentrations for hours. The aim of this study was to test a
      range of central nervous system (CNS) effects under pseudo-steady-state
      conditions. METHODS: To achieve a pseudo-steady state of 0.6 g l(-1), breath
      alcohol concentrations (BrAC) were frequently measured and fed back into a
      spreadsheet-based program to guide intravenous dosing. CNS effects were
      frequently measured throughout the clamp. RESULTS: The clamping paradigm resulted
      in a pseudo-steady-state BrAC of 0.61 g l(-1) (coefficient of variation 6.2%). A
      plateau was maintained from 25 to 300 min and caused significant effects on
      smooth pursuit eye movements [-9.7%, 95% confidence interval (CI) -12.4, -7.1],
      adaptive tracking (-3.4%, 95% CI -4.5, -2.2), visual analogue scale (VAS)
      alertness (-13 mm, 95% CI -20, -6), VAS alcohol effects (16 mm, 95% CI 7, 25) and
      body sway (21.3%, 95% CI 1.8, 45). Some effects (like smooth pursuit eye
      movements) closely followed the relatively stable alcohol concentrations, whereas
      others (such as body sway and VAS alcohol effects) fluctuated during the plateau
      phase. CONCLUSIONS: Most CNS effects of alcohol showed a trend to change over
      time, despite stable concentrations. Other variables remained stable under pseudo
      steady-state conditions. The intravenous clamping method provides precise control
      over BrAC levels and allows frequent repetition of different CNS measurements.
      These features make this technique eminently suitable to study the complex
      pharmacodynamic effects of acute alcohol administration.

PMID- 19843057
TI  - Single-dose pharmacokinetics and pharmacodynamics of anacetrapib, a potent
      cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.
AB  - AIMS: Anacetrapib is an orally active and potent inhibitor of CETP in development
      for the treatment of dyslipidaemia. These studies endeavoured to establish the
      safety, tolerability, pharmacokinetics and pharmacodynamics of rising single
      doses of anacetrapib, administered in fasted or fed conditions, and to
      preliminarily assess the effect of food, age, gender and obesity on the single
      dose pharmacokinetics and pharmacodynamics of anacetrapib. METHODS: Safety,
      tolerability, anacetrapib concentrations and CETP activity were evaluated.
      RESULTS: Anacetrapib was rapidly absorbed, with peak concentrations occurring at
      approximately 4 h post-dose and an apparent terminal half-life ranging from
      approximately 9 to 62 h in the fasted state and from approximately 42 to
      approximately 83 h in the fed state. Plasma AUC and C(max) appeared to increase
      in a less than approximately dose-dependent manner in the fasted state, with an
      apparent plateau in absorption at higher doses. Single doses of anacetrapib
      markedly and dose-dependently inhibited serum CETP activity with peak effects of
      approximately 90% inhibition at t(max) and approximately 58% inhibition at 24 h
      post-dose. An E(max) model best described the plasma anacetrapib concentration vs
      CETP activity relationship with an EC(50) of approximately 22 nm. Food increased
      exposure to anacetrapib; up to approximately two-three-fold with a low-fat meal
      and by up to approximately six-eight fold with a high-fat meal. Anacetrapib
      pharmacokinetics and pharmacodynamics were similar in elderly vs young adults,
      women vs men, and obese vs non-obese young adults. Anacetrapib was well tolerated
      and was not associated with any meaningful increase in blood pressure.
      CONCLUSIONS: Whereas food increased exposure to anacetrapib significantly, age,
      gender and obese status did not meaningfully influence anacetrapib
      pharmacokinetics and pharmacodynamics.

PMID- 19843058
TI  - Population pharmacokinetics and optimal design of paediatric studies for
      famciclovir.
AB  - AIMS: To develop a population pharmacokinetic model for penciclovir (famciclovir
      is a prodrug of penciclovir) in adults and children and suggest an appropriate
      dose for children. Furthermore, to develop a limited sampling design based on
      sampling windows for three different paediatric age groups (1-2, 2-5 and 5-12
      years) using an adequate number of subjects for future pharmacokinetic studies.
      METHODS: Penciclovir plasma data from six different adult and paediatric studies
      were supplied by Novartis. Population pharmacokinetic modelling was undertaken in
      NONMEM version VI. Simulations in MATLAB were used to select an oral paediatric
      dose that gives similar exposure to 500 mg in adults. Optimal sampling times and
      sampling windows were obtained in MATLAB and simulations in NONMEM were used to
      select adequate sample sizes for three paediatric age groups. RESULTS: A two
      compartment, first-order absorption model with an absorption lag time, allometric
      weight models on V(1), V(2) and Q, and an allometric weight model, age and
      creatinine clearance as covariates on CL adequately describe the pharmacokinetics
      of penciclovir in adults and children. Estimated CL (l h(-1) 70 kg(-1)) and V(ss)
      (l.70 kg(-1)) were 31.2 and 83.1, respectively. An oral dose of 10 mg kg(-1) body
      weight in children was predicted to give similar exposure as 500 mg in adults. A
      single sampling windows design (0.25-0.4, 0.5-1, 1.25-1.75, 2.75-3.5 and 7.25-8
      h) for five samples per subject and 10 subjects in each of the paediatric age
      groups is recommended for future studies. CONCLUSIONS: A population
      pharmacokinetic model of penciclovir in adults and children has been developed. A
      prospective study design, including dose adjustment, cohort size and blood
      sampling design has been recommended.

PMID- 19843059
TI  - Development of a drug-disease simulation model for rituximab in follicular non
      Hodgkin's lymphoma.
AB  - AIM: Rituximab has dramatically improved the survival of patients with non
      Hodgkin's lymphomas (NHL), but the dosing regimen currently used should be
      optimized. However, the concentration-effect relationship of rituximab has never
      been described by pharmacokinetic-pharmacodynamic (PK-PD) modelling, precluding
      the simulation of new dosing regimens. The aim of this study was to develop a PK
      PD model of rituximab in relapsed/resistant follicular NHL (FL). METHODS: A model
      describing the relationship between rituximab concentrations and progression-free
      survival (PFS) was developed using data extracted from the pivotal study, which
      evaluated 151 relapsed/resistant FL patients. The influence of FCGR3A genetic
      polymorphism on the efficacy of rituximab was quantified using data from 87
      relapsed/resistant FL patients. The predictive performance of the model was
      analysed using two independent datasets: a study that evaluated rituximab
      combined with chemotherapy [rituximab, cyclophosphamide, vincristine, adriamycin
      and prednisone (R-CHOP)] in 334 relapsed/resistant FL patients and a study that
      evaluated rituximab monotherapy in 47 asymptomatic FL patients with known FCGR3A
      genotype. RESULTS: For R-CHOP, observed and model-predicted PFS (90% confidence
      interval) at 24 months were 0.50 and 0.48 (0.40, 0.56), respectively, for the
      observation arm, and 0.62 and 0.59 (0.50, 0.65), respectively, for the rituximab
      maintenance arm. For rituximab monotherapy, observed and predicted PFS at 24
      months were 0.67 and 0.63, respectively, for FCGR3A-V/V patients, and 0.41 and
      0.36 (0.25, 0.49), respectively, for FCGR3A-F carriers. CONCLUSIONS: Our model
      provides a satisfactory prediction of PFS at 24 months. It can be used to
      simulate new dosing regimens of rituximab in populations of FL patients and
      should improve the design of future clinical trials.

PMID- 19843060
TI  - In vitro and in vivo evaluation of the inhibition potential of risperidone toward
      clozapine biotransformation.
AB  - AIMS: To study the impact of risperidone (RISP) on clozapine (CLZ)
      biotransformation in vitro in microsomal fractions containing varying expression
      of CYP oxidases and in vivo in patients. METHODS: Human liver microsomes (n= 11)
      were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes
      mediate RISP and CLZ oxidation. Inhibition of CLZ oxidation by RISP was assessed.
      Plasma CLZ elimination was estimated in patients with schizophrenia who received
      either CLZ alone or the CLZ-RISP combination (n= 10 per group). RESULTS: (i) The
      CYP3A4 and CYP1A2 inhibitors ketoconazole and fluvoxamine inhibited CLZ oxidation
      to varying extents in individual microsomal fractions. (ii) RISP did not inhibit
      CLZ oxidation, regardless of variations in CYP expression. (iii) RISP co
      administration did not impair CLZ clearance. CONCLUSIONS: No evidence was found
      for CYP-mediated inhibitory or pharmacokinetic interactions between RISP and CLZ.
      Occasional literature reports of such interactions may involve other pathways
      that participate in CLZ disposition.

PMID- 19843061
TI  - Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N
      oxide in healthy subjects.
AB  - AIMS: To evaluate the effect of co-administration of rifampicin, an inducer of
      cytochrome P450 (CYP)3A4, on the pharmacokinetics of roflumilast and roflumilast
      N-oxide. Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor,
      being developed for the treatment of chronic obstructive pulmonary disease.
      Roflumilast is metabolized by CYP3A4 and CYP1A2, with further involvement of
      CYP2C19 and extrahepatic CYP1A1. In vivo, roflumilast N-oxide contributes >90% to
      the total PDE4 inhibitory activity. METHODS: Sixteen healthy male subjects were
      enrolled in an open-label, three-period, fixed-sequence study. They received a
      single oral dose of roflumilast 500 microg on days 1 and 12 and repeated oral
      doses of rifampicin 600 mg once daily on days 5-15. Plasma concentrations of
      roflumilast and roflumilast N-oxide were measured for up to 96 h. Test/Reference
      ratios and 90% confidence intervals (CIs) of geometric means for AUC and C(max)
      of roflumilast and roflumilast N-oxide and for oral apparent clearance (CL/F) of
      roflumilast were estimated. RESULTS: During the steady-state of rifampicin, the
      AUC(0-infinity) of roflumilast decreased by 80% (point estimate 0.21; 90% CI
      0.16, 0.27); C(max) by 68% (0.32; CI 0.26, 0.39); for roflumilast N-oxide, the
      AUC(0-infinity) decreased by 56% (0.44; CI 0.36, 0.55); C(max) increased by 30%
      (1.30; 1.15, 1.48); total PDE4 inhibitory activity decreased by 58% (0.42; 0.38,
      0.48). CONCLUSIONS: Co-administration of rifampicin and roflumilast led to a
      reduction in total PDE4 inhibitory activity of roflumilast by about 58%. The use
      of potent cytochrome P450 inducers may reduce the therapeutic effect of
      roflumilast.

PMID- 19843062
TI  - Clinical pharmacy-led disease and medicine management programme for patients with
      COPD.
AB  - AIM: The aim was to investigate the impact of a disease and medicine management
      programme, focusing on self-management in patients with chronic obstructive
      pulmonary disease (COPD). METHODS: One hundred and seventy-three patients (mean
      age 67 years; 54% female) were recruited; 86 patients were randomly assigned to
      an intervention group and 87 to a usual care (control) group. Intervention
      patients received education on disease state, medications and breathing
      techniques. Patients were given booklets and a customized action plan (antibiotic
      and oral steroid to be initiated promptly by patients for exacerbations).
      Patients were followed up at 6 and 12 months during a scheduled visit. The St
      George's Respiratory Questionnaire (SGRQ), COPD Knowledge and Morisky adherence
      questionnaires were administered to all patients at baseline, 6 and 12 months.
      Outcome measures included hospital admissions, emergency department (ED) visits,
      health-related quality of life (HRQoL) and medication adherence. RESULTS: Over
      the 12-month period in the intervention group, ED visits decreased by 50% (P=
      0.02) and hospitalization by approximately 60% (P= 0.01). On the SGRQ,
      differences reached statistical significance on the symptom (-7.5; P= 0.04) and
      impact (-7.4; P= 0.03) subscales but not on the physical activity subscale. There
      was a significant difference between the intervention and usual care groups
      regarding knowledge scores (75.0 vs. 59.3; P= 0.001) and good adherence to
      medication (77.8% vs. 60.0%, P= 0.019). There was no significant difference
      regarding smoking between study groups. CONCLUSIONS: The clinical pharmacy-led
      management programme can improve adherence, reduce the need for hospital care in
      patients with COPD and improve aspects of their HRQoL.

PMID- 19843063
TI  - Self-medication among children and adolescents in Germany: results of the
      National Health Survey for Children and Adolescents (KiGGS).
AB  - AIMS: Despite the widespread use of self-medication among the child population
      and the potential harm it can do, up-to-date epidemiological data on self
      medication are sparse worldwide. The aim was to investigate the prevalence and
      correlates of self-medication use among non-institutionalized children in
      Germany, focusing on the paediatric self-medications that are most frequently
      used. METHODS: All cases of last-week medicine use were recorded among 17 450
      children aged 0-17 years who participated in the 2003-2006 German Health
      Interview and Examination Survey for Children and Adolescents. Self-medication
      was defined as the use of medicines that had either been bought over the counter
      or obtained from other sources (OS). The complex sample method was used to
      estimate the prevalence of, and factors associated with self-medication use.
      RESULTS: During the previous week 25.2% of participants had used self-medication
      (17.0% used over-the-counter drugs and 9.9% other-sources drugs). Self-medication
      accounted for 38.5% of total medicine use and included all medication classes.
      These clustered among drugs acting on the respiratory system (32.1%), alimentary
      tract and metabolism (21.6%), skin (14.2%) and nervous system (11.3%), as well as
      homoeopathic preparations (8.6%). Vitamin preparations were most frequently used
      with a weighted user prevalence of 4.7% (5.2% vs. 4.1%, P < 0.001, boys vs.
      girls), followed by cough and cold medicines (CCMs) 4.4% (4.3 vs. 4.5, P > 0.05)
      and analgesics 3.7% (3.0% vs. 4.4%, P < 0.001, both boys vs. girls). Overall use
      of aspirin among children <12 years old was 0.3%; use of CCMs was substantial
      (4.4%), particularly among children <6 years old. Use of self-medication was
      closely related to older adolescent ages of between 14 and 17 years (odds ratio
      1.16; 95% confidence interval 1.00, 1.33), children with a poor health status
      (1.29; 1.10, 1.52), with no immigration background (1.55; 1.33, 1.80), from
      families with a higher household income (1.23; 1.06, 1.42) and with mothers with
      a higher educational level (1.37; 1.19, 1.57). CONCLUSIONS: Self-medication use
      is highly prevalent in Germany, particularly among children and adolescents from
      families with a higher socioeconomic status. Self-medication in younger children
      using such drugs as CCMs and aspirin suggested inappropriate drug use and
      potential risks. This should be closely monitored and warrants an education
      programme for parents in Germany.

PMID- 19843064
TI  - Pregnancy outcome, thyroid dysfunction and fetal goitre after in utero exposure
      to propylthiouracil: a controlled cohort study.
AB  - AIMS: Propylthiouracil (PTU) is presently considered to be the treatment of
      choice for hyperthyroidism in pregnancy. It is known to cross the human placenta,
      and therefore may affect the fetus. The major aims of this study were to evaluate
      the rate of major anomalies and to report the rate of fetal goitre, accompanied
      by hypothyroidism, in fetuses/ newborns of mothers after in utero exposure to
      PTU. METHODS: Prospective observational controlled cohort study of PTU-exposed
      pregnancies of women counselled by the Israeli Teratology Information Service
      between the years 1994 and 2004 compared with women exposed to nonteratogens.
      RESULTS: We followed up 115 PTU-exposed pregnancies and 1141 controls. The rate
      of major anomalies was comparable between the groups [PTU 1/80 (1.3%), control
      34/1066 (3.2%), P= 0.507]. Hypothyroidism was found in 9.5% of fetuses/neonates
      (56.8% of whom with goitre). Hyperthyroidism, possibly resulting from maternal
      disease, was found in 10.3%. Goitres prenatally diagnosed by ultrasound were
      successfully treated in utero by maternal dose adjustment. In most cases neonatal
      thyroid functions normalized during the first month of life without any
      treatment. Median neonatal birth weight was lower [PTU 3145 g (2655-3537) vs.
      control 3300 g (2968-3600), P= 0.018]. CONCLUSIONS: PTU does not seem to be a
      major human teratogen. However, it could cause fetal/neonatal hypothyroidism with
      or without goitre. Fetal thyroid size monitoring and neonatal thyroid function
      tests are important for appropriate prevention and treatment.

PMID- 19843065
TI  - Trends in prescribing and self-poisoning in relation to UK regulatory authority
      warnings against use of SSRI antidepressants in under-18-year-olds.
AB  - AIMS: To assess the impact of the UK Medicines and Healthcare products Regulatory
      Authority (MHRA) warning in December 2003 not to prescribe selective serotonin
      reuptake inhibitor (SSRI) antidepressants, except fluoxetine, to under-18-year
      olds. METHODS: Interrupted time series analysis of prescriptions (UK) and general
      hospital presentations for nonfatal self-poisoning (three centres in England) for
      2000-2006. RESULTS: Following the MHRA warning in December 2003 there were
      significant decreases in prescribing of SSRI antidepressants (conservative
      estimate 51%) to young people aged 12-19 years. Surprisingly, this decrease also
      affected fluoxetine (conservative estimate 20%) and tricyclics (conservative
      estimate 27%). Nonfatal self-poisoning in this age group following the warning
      also declined significantly for SSRIs (conservative estimate 44%), but not for
      fluoxetine, tricyclic antidepressants, or all drugs and other substances. Rates
      of nonfatal self-harm did not change significantly over the study period.
      CONCLUSIONS: The reduction in both prescribing and self-poisoning with SSRI
      antidepressants (except fluoxetine) following the MHRA warning is in keeping with
      reduced availability of these drugs. There was some evidence of substitution from
      other SSRIs to fluoxetine for use in self-poisoning. Importantly, overall rates
      of nonfatal self-harm and self-poisoning did not change, indicating no
      substitution of method or increases in self-injury.

PMID- 19843066
TI  - Investigation of endothelial function by pulse contour analysis: a protocol for
      drug administration and timing of pulse contour assessment.
AB  - AIMS: Pulse contour analysis (PCA) obtained by finger photoplethysmography
      produces a digital volume pulse (DVP) including an inflection point in its down
      slope. The reflection index (RI: ratio of the inflection point height over the
      maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose
      and time interval for assessing endothelial function using PCA in healthy
      volunteers and patients with severe coronary artery disease. METHODS: Time and
      dose to RI response relationships were constructed in 16 volunteers and nine
      patients to inhaled salbutamol (100-400 microg) or sublingual nitroglycerin (NTG;
      25-400 microg). RESULTS: For the volunteers, the time to maximum RI response to
      inhaled salbutamol and sublingual NTG was 10.73 +/- 0.41 and 3.66 +/- 0.21 min,
      respectively. A plateau in the RI response to salbutamol occurred between 5 and
      15 min after inhalation and results were averaged over this period. A dose
      dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05
      and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By
      contrast, in patients with severe coronary artery disease inhaled salbutamol (100
      400 microg) did not cause a significant change in RI. CONCLUSIONS: In healthy
      volunteers the RI response to inhaled salbutamol (100-200 microg) averaged over 5
      15 min after administration may be used to investigate endothelial function by
      PCA. The response to sublingual NTG (50 microg) should be determined at 4 min.
      This technique may not be suitable for the assessment of endothelial function in
      subjects with extensive coronary artery disease owing to the small responses
      observed and potential confounding effect of vasoactive medication.

PMID- 19843067
TI  - Short term effects of spironolactone on blood lipid profile: a 3-month study on a
      cohort of young women with hirsutism.
AB  - AIMS: To investigate the effects of spironolactone on serum lipids in women with
      hirsutism over a 3-month period. METHODS: In a prospective setting, 27 hirsute
      women (20 with polycystic ovary syndrome and seven with idiopathic hirsutism)
      with a mean age of 23.0 +/- 5.1 years were studied at baseline and 3 months after
      receiving a daily dose of 100 mg of spironolactone. Patients did not receive any
      other medications and did not go through a specific diet during the study. Lipid
      profile, fasting blood glucose, testosterone, dehydroepiandrosterone sulphate
      (DHEAS) and prolactin (PRL) were measured at baseline and 3 months after therapy.
      RESULTS: Mean body mass index of patients was 26.1 +/- 5.1 kg m(-2) before
      treatment and 25.9 +/- 5.7 kg m(-2) after treatment (NS). The therapy was
      associated with a significant decline of mean high-density lipoprotein (HDL),
      39.5 mg dl(-1)[95% confidence interval (CI) 35.6, 43.4]vs. 32.2 mg dl(-1) (95% CI
      29.2, 35.2), and a significant increase in mean low-density lipoprotein (LDL),
      133.1 mg dl(-1) (95% CI 120.2, 146) vs. 150.8 mg dl(-1) (95% CI 139.1, 162.5),
      and cholesterol/HDL ratio, 5 (95% CI 4.4, 5.6) vs. 6.4 (95% CI 5.7, 7.1) (P <
      0.05). No significant change was noted in total cholesterol, triglyceride or
      fasting blood glucose levels. Serum values of testosterone, DHEAS and PRL
      decreased significantly after 3 months of therapy (P < 0.05). CONCLUSIONS:
      Spironolactone might have adverse effects on serum lipoprotein levels by
      increasing LDL and decreasing HDL over a short course of treatment. While
      treating hirsutism with spironolactone, special care should be given to women
      with metabolic disorders such as dyslipidaemia.

PMID- 19843069
TI  - Fibroblast growth factor receptor 3 mutation in voided urine is a useful
      diagnostic marker and significant indicator of tumor recurrence in non-muscle
      invasive bladder cancer.
AB  - The fibroblast growth factor receptor (FGFR)-3 gene encodes a receptor tyrosine
      kinase that is frequently mutated in non-muscle invasive bladder cancer (NMIBC).
      A sensitive and quantitative assay using peptide nucleic acid-mediated real-time
      PCR was developed for detecting FGFR3 mutations in the urine samples and
      evaluated as a molecular marker for detecting intravesical recurrence of NMIBC in
      patients undergoing transurethral resection of bladder tumor. FGFR3 mutation was
      examined in tumor tissues and serially taken pre- and postoperative urine
      sediments in 45 NMIBC patients with a median follow up of 32 months. FGFR3
      mutations were detected in 53.3% (24/45) of primary tumor tissues, among which
      intravesical recurrence developed in 37.5% (9/24) of cases. FGFR3 mutation in the
      primary tumor was not a significant prognostic indicator for recurrence, while
      the proportion of FGFR3 mutation (i.e. tumor cellularity was >or=11%) in the
      preoperative urine sediments was a significant indicator for recurrence in
      patients with FGFR3 mutations in the primary tumors. FGFR3 mutations were
      detected in 78% (7/9) of postoperative urine samples from recurrent cases with
      FGFR3 mutations in the tumor, while no mutations were detected in the urine of 15
      non-recurrent cases. Urine cytology was negative in all cases with FGFR3
      mutations in the primary tumors, while the sensitivity of cytological examination
      was as high as 56% (5/9) in cases showing wild-type FGFR3 in the primary tumors.
      Urine FGFR3 mutation assay and cytological examination may be available in the
      future as complementary diagnostic modalities in postoperative management of
      NMIBC.

PMID- 19843070
TI  - Contribution of BCR-ABL-independent activation of ERK1/2 to acquired imatinib
      resistance in K562 chronic myeloid leukemia cells.
AB  - BCR-ABL tyrosine kinase, generated from the reciprocal chromosomal translocation
      t(9;22), causes chronic myeloid leukemia (CML). BCR-ABL is inhibited by imatinib;
      however, several mechanisms of imatinib resistance have been proposed that
      account for loss of imatinib efficacy in patients with CML. Previously, we showed
      that overexpression of the efflux drug transporter P-glycoprotein partially
      contributed to imatinib resistance in imatinib-resistant K562 CML cells having no
      BCR-ABL mutations. To explain an additional mechanism of drug resistance, we
      established a subclone (K562/R) of the cells and examined the BCR-ABL signaling
      pathway in these and wild-type K562 (K562/W) cells. We found the K562/R cells
      were 15 times more resistant to imatinib than their wild-type counterparts. In
      both cell lines, BCR-ABL and its downstream signaling molecules, such as ERK1/2,
      ERK5, STAT5, and AKT, were phosphorylated in the absence of imatinib. In both
      cell lines, imatinib effectively reduced the phosphorylation of all the above,
      except ERK1/2, whose phosphorylation was, interestingly, only inhibited in the
      wild-type cells. We then observed that phospho-ERK1/2 levels decreased in the
      presence of siRNA targeting BCR-ABL, again, only in the K562/W cells. However,
      using an ERK1/2 inhibitor, U0126, we found that we could reduce phospho-ERK1/2
      levels in K562/R cells and restore their sensitivity to imatinib. Taken together,
      we conclude that the BCR-ABL-independent activation of ERK1/2 contributes to
      imatinib resistance in K562/R cells, and that ERK1/2 could be a target for the
      treatment of CML patients whose imatinib resistance is due to this mechanism.

PMID- 19843071
TI  - Silencing of galectin-3 changes the gene expression and augments the sensitivity
      of gastric cancer cells to chemotherapeutic agents.
AB  - Galectin-3 is known to modulate cell proliferation and apoptosis and is highly
      expressed in human cancers, but its function in gastric cancer is still
      controversial. Here, we examined the role of galectin-3 in gastric cancer cells
      by silencing it with synthetic double-stranded siRNA. After silencing of galectin
      3, cell numbers decreased and cell shape changed. Galectin-3 siRNA treatment also
      induced G(1) arrest. DNA microarray analysis was used to assess changes in gene
      expression following galectin-3 silencing. We found that silencing of galectin-3
      caused changes in gene expression. RT-PCR and real-time PCR were utilized for
      validation of the changes found in microarray studies. Western blot analysis
      confirmed changes in the expression of proteins of interest: cyclin D1, survivin,
      XIAP, XAF, PUMA, and GADD45alpha. Generally, it tended to increase the expression
      of several pro-apoptotic genes, and to decrease the expression of cell cycle
      progressive genes. We also confirmed that changes in the expression of these
      genes were caused by galectin-3 overexpression. Finally, we demonstrated that
      silencing of galectin-3 enhanced apoptosis induction with chemotherapeutic agents
      by further reducing the expression of anti-apoptotic and/or cell survival
      molecules such as survivin, cyclin D1, and XIAP, and increasing the expression of
      pro-apoptotic XAF-1. We conclude that galectin-3 is involved in cancer
      progression and malignancy by modulating the expression of several relevant
      genes, and inhibition of galectin-3 may be an approach to improve chemotherapy of
      gastric cancers.

PMID- 19843072
TI  - Phase I study of TLR9 agonist PF-3512676 in combination with carboplatin and
      paclitaxel in patients with advanced non-small-cell lung cancer.
AB  - This phase I, open-label study investigated the Toll-like receptor 9 agonist, PF
      3512676, in combination with carboplatin and paclitaxel in Japanese patients with
      advanced, non-small-cell lung cancer (NSCLC). Patients (n = 12) with treatment
      naive stage IIIB or IV NSCLC received single-agent PF-3512676 subcutaneously once
      during the first 7 days (monotherapy phase) in three escalating dose levels (0.1,
      0.2, and 0.4 mg/kg) followed by a combination phase during which patients
      received 0.1 or 0.2 mg/kg PF-3512676 subcutaneously on days 8 and 15 of each 3
      week cycle of carboplatin (area under the curve, 6 mg x min/mL) and paclitaxel
      (200 mg/m(2)). Safety and pharmacokinetics of PF-3512676 were assessed during
      monotherapy and combination therapy phases. PF-3512676 was tolerable as
      monotherapy or in combination with chemotherapy in patients with NSCLC. Most
      common treatment-related, non-hematologic adverse events (AEs) throughout the
      study were injection-site reactions (n = 12, 100%) and flu-like symptoms (n = 11,
      91.7%) that were each grade 1 or 2 in all but one patient. All patients
      experienced neutropenia and leukopenia (>or=grade 3 in 11 [91.7%] and seven
      [58.3%] patients, respectively). One patient in dose level 2 had a dose-limiting
      toxicity: grade 3 rash and grade 3 increase in gamma-glutamyltransferase during
      combination therapy. Mean PF-3512676 half-life ranged from 4.8 to 21.6 h (longer
      with higher doses). Four (33%) patients had objective responses (one complete
      response, three partial responses), and seven (58%) patients achieved stable
      disease. PF-3512676 as monotherapy and in combination with chemotherapy had an
      acceptable safety profile in Japanese patients with treatment-naive NSCLC.

PMID- 19843073
TI  - LAPTM4B-35, a novel tetratransmembrane protein and its PPRP motif play critical
      roles in proliferation and metastatic potential of hepatocellular carcinoma
      cells.
AB  - Lysosomal protein transmembrane 4 beta (LAPTM4B) was originally identified as a
      hepatocellular carcinoma (HCC)-associated gene. This gene and its protein product
      LAPTM4B-35, are both overexpressed in a variety of human cancers. However, its
      specific role in cell transformation and malignancy has remained elusive. In the
      present study we investigated the effects of LAPTM4B-35 overexpression on the
      malignant phenotypic features in the HLE cell line. Our data show that
      overexpression of LAPTM4B-35 promotes cell proliferation, exogenous growth
      stimulating factor-independent and anchorage-independent growth, and enhances
      metastatic potential, including promotion of both cell migration and invasion.
      Study of the underlying mechanisms demonstrated alterations of molecular events
      involved in these processes, which included upregulation of proliferation
      promoting transcription factors such as c-Myc, c-Jun, and c-Fos, and cell cycle
      promoting proteins such as cyclin D1 and cyclin E. In addition, mutagenesis study
      showed that the PPRP motif in the N-terminal region of LAPTM4B-35 plays a
      critical role in promoting proliferation, migration, and invasion, as well as in
      the upregulation of the oncoproteins noted above. These data offer insight into
      the mechanism by which this novel tetratransmembrane protein contributes to the
      pathogenesis of liver cancer, and suggest that it may be a potential target for
      cancer therapy.

PMID- 19843074
TI  - Activity prediction and structural insights of extracellular signal-regulated
      kinase 2 inhibitors with molecular dynamics simulations.
AB  - A computational application to predict, probe and interpret the activities of a
      series of congeneric compounds inhibiting extracellular signal-regulated kinase 2
      protein kinase is presented. The study shows that molecular dynamics coupled with
      molecular mechanics Poisson-Boltzmann solvent accessible surface area free energy
      estimation is a suitable tool for investigating the experimental binding
      activities of ligands to protein kinases. Computed and experimental binding
      activities were found to be significantly correlated. Moreover, the
      interpretation of the X-ray co-crystal structure in conjunction with
      computational results shows that the hinge region of the protein insure the
      principal binding site via multiple hydrogen bonding interactions, whereas fine
      modulation of biological activities along the series is accomplished through the
      combination of weak and strong interactions that compete with water. These are
      located in the substituent moieties of the ligands interfacing with the DFG
      motif, the sugar region and the hydrophobic pocket of extracellular signal
      regulated kinase 2. The study suggests that a wider interaction framework that is
      well beyond the hinge region is required to predict and rationalize at molecular
      level the experimental biological activities of congeneric compound series.

PMID- 19843075
TI  - Ligand-based 3D-QSAR studies of physostigmine analogues as acetylcholinesterase
      inhibitors.
AB  - Natural alkaloid Physostigmine is one of the most potent pseudo-irreversible
      inhibitor of Acetylcholinesterase. It was found to accelerate long-term memory
      process, but due to its short half life and variable bioavailability, has
      inconsistent clinical efficacy. 3D-QSAR studies based on the comparative
      molecular field analysis and comparative molecular similarity indices analysis
      were applied to a set of 40 Physostigmine derivatives which are divided into two
      classes: A and B. The study was conducted to obtain a highly reliable and
      extensive dynamic QSAR model based on alignment procedure with co-crystallized
      Ganstigmine as template. The strategy yielded significant 3D-QSAR models with the
      cross-validated q(2) values 0.762 and 0.754 for comparative molecular field
      analysis and comparative molecular similarity indices analysis, respectively.
      Resulted models were validated by external set of eight compounds yielding high
      correlation coefficient r(2) values of 0.730 and 0.720 for comparative molecular
      field analysis and comparative molecular similarity indices analysis,
      respectively. Furthermore, the analysis of comparative molecular field analysis
      and comparative molecular similarity indices analysis contour maps within the
      active site of AChE were conducted in order to understand the interactions
      between the receptor and the Physostigmine derivatives. This study will
      facilitate the rational design of more potent Physostigmine compounds which might
      have better activity and reduce toxicity for the treatment of Alzheimer disease.

PMID- 19843076
TI  - Resveratrol is not a direct activator of SIRT1 enzyme activity.
AB  - Resveratrol is a plant polyphenol capable of exerting beneficial metabolic
      effects which are thought to be mediated in large by the activation of the NAD(+)
      dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be
      a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys-SIRT1 peptide
      substrate), recent reports indicate that this finding might be an experimental
      artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys-SIRT1
      peptide is an artificial SIRT1 substrate because in the absence of the covalently
      linked fluorophore the peptide itself is not a substrate of the enzyme, (ii)
      resveratrol does not activate SIRT1 in vitro in the presence of either a p53
      derived peptide substrate or acetylated PGC-1alpha isolated from cells, and (iii)
      although SIRT1 deacetylates PGC-1alpha in both in vitro and cell-based assays,
      resveratrol did not activate SIRT1 under these conditions. Based on these
      observations, we conclude that the pharmacological effects of resveratrol in
      various models are unlikely to be mediated by a direct enhancement of the
      catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the
      overall utility of resveratrol as a pharmacological tool to directly activate
      SIRT1.

PMID- 19843077
TI  - QM/MM study of epitope peptides binding to HLA-A*0201: the roles of anchor
      residues and water.
AB  - A hybrid quantum mechanics/molecular mechanics scheme is described to explore the
      structural basis and energetic behavior of short peptide segments binding to HLA
      A*0201. This method was used to analyze 50 structurally diverse non-americ
      peptides and results showed that the quantum mechanics/molecular mechanics
      derived interaction energy, in conjugation with empirical desolvation free
      energy, linearly correlate well with the experimentally determined affinity.
      Further systematic investigations of several HLA-A*0201-peptide complexes
      confirmed the importance of anchor residues and water molecules in peptide
      binding, and quantitatively showed that: (i) the primary and second anchor
      residues provide a larger binding energy contribution (>3 kcal/mol) than the non
      anchor residues (<2 kcal/mol), (ii) native hydrophobic anchor residues replaced
      by polar amino acids will lead to a significant destabilization for bound
      complexes (>4 kcal/mol), and (iii) water molecules contribute significantly to
      stabilization of the complexes (>8 kcal/mol). We believe that this work is
      helpful for elucidating the roles of anchor residues and water molecules in
      peptides recognized and bound by HLA-A*0201.

PMID- 19843078
TI  - Combined 3D-QSAR modeling and molecular docking study on quinoline derivatives as
      inhibitors of P-selectin.
AB  - P-selectin is a promising target for developing novel atherosclerosis drugs. To
      understand the structure-activity correlation of quinolines-based P-selectin
      inhibitors, we have carried out a combined molecular docking and three
      dimensional quantitative structure-activity relationship (3D-QSAR) modeling
      study. The study has resulted in two types of satisfactory 3D-QSAR models,
      including the CoMFA model (r(2), 0.863; q(2), 0.589) and CoMSIA model (r(2),
      0.866; q(2), 0.636), to predict the biological activity of new compounds. The
      detailed microscopic structures of P-selectin binding with inhibitors have been
      studied by molecular docking. We have also developed docking based 3D-QSAR models
      (CoMFA with r(2), 0.934; q(2), 0.591; CoMSIA with r(2), 0.896; q(2), 0.573). The
      contour maps obtained from the 3D-QSAR models in combination with the docked
      binding structures help to better interpret the structure-activity relationship.
      All of the structural insights obtained from both the 3D-QSAR contour maps and
      molecular docking are consistent with the available experimental activity data.
      The satisfactory results strongly suggest that the developed 3D-QSAR models and
      the obtained P-selectin-inhibitor binding structures are reasonable for the
      prediction of the activity of new inhibitors and in future drug design.

PMID- 19843081
TI  - Morphoea-like plaques revealing an eosinophilic (Shulman) fasciitis.
AB  - Eosinophilic fasciitis (EF) is a connective-tissue disease characterized by
      thickened fascia. Involvement of the dermis may occur during the progression of
      the disease, characterized clinically by morphoea-like plaques (MLPs). This more
      superficial feature of EF carries a poor prognosis, suggestive of refractory EF
      that requires intensive therapy. We report a case in which morphoea-like plaques
      occurred before the EF. This case and previous cases of MLPs show some
      differences between MLPs and classic morphoea. Clinically, MLPs present with ill
      defined brown plaques, with no lilac ring or ivory colour. Histologically, there
      is a more marked inflammatory infiltrate and an increase in the number of
      eosinophils. The discovery of MLPs at an early stage should prompt examination of
      the fascia with magnetic resonance imaging or surgical biopsy, and aggressive
      treatment.

PMID- 19843080
TI  - The design, synthesis and potential utility of fluorescence probes that target
      DFG-out conformation of p38alpha for high throughput screening binding assay.
AB  - The design, synthesis and utility of fluorescence probes that bind to the DFG-out
      conformation of p38alpha kinase are described. Probes that demonstrate good
      affinity for p38alpha, have been identified and one of the probes, PF-04438255,
      has been successfully used in an high throughput screening (HTS) assay to
      identify two novel non-classical p38alpha inhibitors. In addition, a cascade
      activity assay was utilized to validate the selective binding of these non
      classical kinase inhibitors to the unactive form of the enzyme.

PMID- 19843082
TI  - Langerhans cell histiocytosis associated with breast carcinoma successfully
      treated with topical imiquimod.
AB  - Langerhans cell histiocytosis (LCH) encompasses a group of disorders
      characterized by the proliferation and infiltration of Langerhans cells within
      internal organs and/or skin. There is often multiorgan involvement; isolated
      cutaneous LCH is less common. The aetiology of cutaneous LCH remains uncertain,
      and debate remains as to whether LCH represents a neoplastic condition or is
      simply reactive. We report a 53-year-old woman who developed isolated cutaneous
      LCH 15 months after being diagnosed with infiltrating ductal carcinoma of the
      left breast. The LCH was treated with topical imiquimod, resulting in clinical
      and histological resolution. Our case highlights the rare association between
      cutaneous LCH and breast carcinoma, and the clinical and histological response
      that can be achieved with topical imiquimod. After a diagnosis of LCH, patients
      require long-term follow-up, due to the risk of recurrence and/or development of
      a subsequent malignancy.

PMID- 19843083
TI  - Angiokeratoma: a cutaneous marker of Fabry's disease.
AB  - The initial symptoms of Fabry's disease (FD) may seem harmless and may delay its
      diagnosis. A survey and screening for FD were performed on men with biopsy-proven
      angiokeratoma and some of their relatives (n = 29). Three patients were
      identified. Dermatologists should be aware of this prominent early feature and
      investigate unexplained cutaneous vascular lesions to detect FD.

PMID- 19843084
TI  - A randomized double-blind controlled trial to compare a triclosan-containing
      emollient with vehicle for the treatment of atopic dermatitis.
AB  - The use of topical antiseptics in the treatment of atopic dermatitis (AD) has
      previously been explored. However, no triclosan-containing leave-on emollient has
      been evaluated previously, to our knowledge. The aims of this study were to
      assess the safety and efficacy of an emollient containing triclosan compared with
      the emollient alone (vehicle) for the treatment of AD. Eligible patients with
      mild to moderate AD were randomized to receive either the study cream or vehicle.
      All patients also received a low-potency corticosteroid cream to use during the
      treatment phase of the study if necessary. Patients were assessed for severity
      according to the SCORing Atopic Dermatitis (SCORAD) Index, amount of
      corticosteroid used, patient assessment of cream, and adverse events (AEs). In
      total, 60 patients received either the study cream or vehicle, and an intention
      to-treat analysis was performed. At day 14, there was a significant decrease in
      SCORAD from baseline for the study cream compared with vehicle (P < 0.05). At day
      27, although there was an improved mean reduction from baseline, this was no
      longer significant (P > 0.05). Only four patients had mild treatment-related AEs.
      The mean total amount of topical steroid applied by the patients using the study
      was significantly lower than that used by controls (P = 0.40). Triclosan
      containing leave-on emollient was safe and highly acceptable to patients.
      However, the overall benefit on day 27 was not significant. Nevertheless, the
      amount of topical steroid used by patients was significantly less with the study
      cream than with the vehicle, thus further studies are needed to confirm its
      steroid-sparing effect.

PMID- 19843085
TI  - Serum cytokines and growth factor levels in Japanese patients with psoriasis.
AB  - BACKGROUND: Although the precise pathomechanism of psoriasis is still unknown,
      various cytokines and growth factors derived from T cells, dendritic cells or
      keratinocytes, are critically involved in this disease. There have been several
      studies determining the serum levels of cytokines in patients with psoriasis, but
      with conflicting results. The levels of various cytokines and growth factors were
      measured in the sera of patients with psoriasis and compared with those of
      healthy controls. The correlation with disease severity was also determined.
      METHODS: Sera were collected from 122 patients with psoriasis and 78 healthy
      controls for ELISA analysis to evaluate the levels of cytokines and growth
      factors. The severity of psoriasis was determined by the Psoriasis Area and
      Severity Index (PASI). RESULTS: Serum levels of tumour necrosis factor (TNF)
      alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-6, IL-7, IL-8, IL-12, IL
      17, IL-18 and vascular endothelial growth factor (VEGF) were significantly
      increased in patients with psoriasis compared with those of healthy controls. The
      serum levels of IL-2, soluble intercellular adhesion molecule-1, epidermal growth
      factor, hepatocyte growth factor and amphiregulin were not significantly
      different from those of healthy controls. Increased serum levels of TNF-alpha,
      IFN-gamma, IL-12, IL-17, IL-18 and VEGF correlated with PASI. Furthermore, these
      cytokine levels were decreased after psoriasis treatment. In contrast, serum
      levels of IL-10 were decreased in psoriasis and negatively correlated with PASI.
      DISCUSSION: Serum levels of TNF-alpha, IFN-gamma, IL2, IL-6, IL-7, IL-8, IL-12,
      IL-17, IL-18 and VEGF were positively correlated and that of IL-10 was negatively
      correlated with PASI in Japanese patients with psoriasis. These parameters might
      be useful for determining the disease activity of psoriasis.

PMID- 19843086
TI  - Possible association of the CD4 gene polymorphism with vitiligo in an Iranian
      population.
AB  - BACKGROUND: Vitiligo is an acquired idiopathic and polygenic disorder with
      progressive depigmentation of circumscribed patches. Its exact pathogenesis is
      unknown. The CD4 gene plays an important role in the cell-mediated immune
      response and its association with type 1 diabetes mellitus, which is an
      autoimmune disease, has been previously reported. METHODS: Based on the
      assumption that autoimmunity is also involved in vitiligo, the CD4 gene was
      selected for study using a candidate gene approach. The pyrimidine-rich
      pentanucleotide repeat length polymorphism located in the promoter of the gene
      was studied. We screened 144 unrelated Iranian patients with vitiligo and 144
      healthy matched controls by PCR. RESULTS: The CD4*A4 allele has a susceptibility
      association with the development of vitiligo in the Iranian population (OR =
      1.68, 95% CI 1.18-2.42; P < 0.01, P(c) = 0.02). When we compared CD4*A4
      containing genotypes in the case and control groups, even more significant
      positive association was identified (OR = 2.02, 95% CI 1.26-3.22; P < 0.01 and
      P(c) < 0.01). The CD4 gene polymorphism has a modest association with the
      development of vitiligo in Iranian patients.

PMID- 19843087
TI  - Kimura's disease mimicking an earlobe keloid.
AB  - Kimura's disease (KD) is a rare chronic inflammatory disorder of unknown
      aetiology. It usually presents as soft-tissue masses predominantly in the head or
      neck region. We report a case of an asymptomatic tumour on the left earlobe
      mimicking a keloid. The tumour was histopathologically diagnosed as KD. This case
      suggests the importance of conducting skin biopsies of keloidal lesions on head
      and neck regions, particularly in patients who have peripheral eosinophilia and
      increased IgE levels.

PMID- 19843088
TI  - Complement activation pathways in murine immune complex-induced arthritis and in
      C3a and C5a generation in vitro.
AB  - The alternative pathway (AP) of complement alone is capable of mediating immune
      complex-induced arthritis in the collagen antibody-induced arthritis (CAIA) model
      in mice. Whether the classical pathway (CP) or lectin pathway (LP) alone can
      mediate CAIA is not known. Using mice genetically deficient in different
      complement components, our results reported herein establish that the CP and LP
      alone are each incapable of mediating CAIA. A lower level or absence of C3 and/or
      C5 activation by the CP may be possible explanations for the importance of the AP
      in CAIA and in many murine models of disease. In addition, other investigators
      have reported that CP C5 convertase activity is absent in mouse sera. To address
      these questions, we employed an in vitro system of adherent immunoglobulin (Ig)G
      induced complement activation using plates coated with murine anti-collagen
      monoclonal antibody (mAb). These experiments used complement-deficient mouse sera
      and wild-type mouse or normal human sera under conditions inactivating either the
      CP (Ca(++) deficiency) or the AP (mAb inhibitory to factor B). Robust generation
      of both C3a and C5a by either the AP or CP alone were observed with both mouse
      and human sera, although there were some small differences between the species of
      sera. We conclude that neither the CP nor LP alone is capable of mediating CAIA
      in vivo and that mouse sera exhibits a high level of IgG-induced C5a generation
      in vitro through either the CP or AP.

PMID- 19843089
TI  - Human papillomavirus 16-specific T cell responses in classic HPV-related vulvar
      intra-epithelial neoplasia. Determination of strongly immunogenic regions from E6
      and E7 proteins.
AB  - Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens
      was studied in 16 patients affected with classic vulvar intra-epithelial
      neoplasia (VIN), also known as bowenoid papulosis (BP). Ten patients had blood
      lymphocyte proliferative T cell responses directed against E6/2 (14-34) and/or
      E6/4 (45-68) peptides, which were identified in the present study as
      immunodominant among HPV-16 E6 and E7 large peptides. Ex vivo enzyme-linked
      immunospot-interferon (IFN)-gamma assay was positive in three patients who had
      proliferative responses. Twelve months later, proliferative T cell responses
      remained detectable in only six women and the immunodominant antigens remained
      the E6/2 (14-34) and E6/4 (45-68) peptides. The latter large fragments of
      peptides contained many epitopes able to bind to at least seven human leucocyte
      antigen (HLA) class I molecules and were strong binders to seven HLA-DR class II
      molecules. In order to build a therapeutic anti-HPV-16 vaccine, E6/2 (14-34) and
      E6/4 (45-68) fragments thus appear to be good candidates to increase HPV-specific
      effector T lymphocyte responses and clear classic VIN (BP) disease lesions.

PMID- 19843090
TI  - Activation profile of Toll-like receptors of peripheral blood lymphocytes in
      patients with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated
      with aberrant activation of T and B lymphocytes for the production of
      inflammatory cytokines and autoreactive antibodies. Animal studies of SLE have
      indicated that Toll-like receptors (TLR) are important in the pathogenesis of
      murine lupus. In the present clinical study, differential protein expressions of
      TLR-1-9 of monocytes and different lymphocyte subsets from patients with SLE and
      normal control subjects were determined by flow cytometry. Results showed that
      the expression of intracellular TLRs (TLR-3, -8, -9) and extracellular TLRs (TLR
      1, -2, -4, -5, -6) were elevated in monocytes, CD4(+) T lymphocytes, CD8(+) T
      lymphocytes and B lymphocytes of SLE patients compared to control subjects (all P
      < 0.001). Moreover, cell surface expression of TLR-4 on CD4(+) T lymphocytes and
      CD8(+) T lymphocytes, and TLR-6 on B lymphocytes, were correlated positively with
      SLE disease activity index (SLEDAI) (TLR-4 on CD4(+) T lymphocytes and CD8(+) T
      lymphocytes: r = 0.536, P = 0.04; r = 0.713, P = 0.003; TLR-6 in B lymphocytes: r
      = 0.572, P = 0.026). In concordance with the above results, there is an
      observable increased relative induction (%) of inflammatory cytokine interleukin
      (IL)-1beta, IL-6, IL-10 and IL-12, chemokines CCL2, CXCL8, CCL5 and CXCL10 from
      peripheral blood mononuclear cells (PBMC) upon differential stimulation by PolyIC
      (TLR-3 ligand), lipopolysaccharide (TLR-4 ligand), peptidoglycan (TLR-2 ligand),
      flagellin (TLR-5 ligand), R837 (TLR-7 ligand) and CpG DNA (TLR-9 ligand) in SLE
      patients compared to controls. These results suggest that the innate immune
      response for extracellular pathogens and self-originated DNA plays
      immunopathological roles via TLR activation in SLE.

PMID- 19843092
TI  - Bland-Altman beyond the basics: creating confidence with badly behaved data.

PMID- 19843091
TI  - Frontiers in research reviews: in vitro approaches to the study of neural control
      of autonomic and respiratory functions. Introduction.

PMID- 19843093
TI  - Functional expression of cystic fibrosis transmembrane conductance regulator in
      mouse chondrocytes.
AB  - 1. Cystic fibrosis transmembrane conductance regulator (CFTR) is well known for
      its role in the cystic fibrosis (CF). Recent studies have shown that CF patients
      and CFTR-deficient mice exhibit a severe abnormal skeletal phenotype, indicating
      that CFTR may play a role in bone development and pathophysiological processes.
      However, it is not known whether CFTR has a direct or indirect effect on bone
      formation. The aim of the present study was to detect the expression and function
      of CFTR in mouse chondrocytes. 2. Reverse transcription-polymerase chain
      reaction, western blotting and immunofluorescence were used to characterize the
      expression of CFTR in primary isolated mouse chondrocytes. Expression of CFTR
      mRNA and protein was detectable in mouse chondrocytes. Importantly, whole-cell
      patch-clamp analysis demonstrated that CFTR in mouse chondrocytes is functional
      as a cAMP-dependent Cl(-) channel that is inhibited by CFTRinh-172. 3. Thus, the
      results of the present study demonstrate that functional CFTR is expressed in
      mouse chondrocytes, which offers essential evidence for the potential direct role
      of CFTR in physiological and pathological processes of bone.

PMID- 19843094
TI  - Inhibitors of slit protein interactions with the heparan sulphate proteoglycan
      glypican-1: potential agents for the treatment of spinal cord injury.
AB  - 1. The heparan sulphate proteoglycan glypican-1 is a major high-affinity ligand
      of the Slit proteins. 2. Messenger RNA for both Slit-2 and glypican-1 is strongly
      upregulated and coexpressed in the reactive astrocytes of injured adult brain,
      suggesting a possible function of Slit proteins and glypican-1 in the adult
      central nervous system as significant components of the inhibitory environment
      that prevents axonal regeneration after injury. 3. Based on the hypothesis that
      adverse effects on axonal regeneration may be due to a glypican-Slit complex or
      the retention of glypican-binding C-terminal proteolytic processing fragments of
      Slit at the injury site, we used ELISA to examine a number of small molecules and
      low molecular weight heparin analogues for their ability to inhibit glypican-Slit
      interactions. 4. Our studies have led to the identification of several potent
      inhibitors with a favourable therapeutic profile that can now be tested in a
      spinal cord injury model. Among the most promising of these are a low molecular
      weight heparin produced by periodate oxidation and having no significant
      anticoagulant activity, the chemically sulphonated yeast-derived phosphomannan PI
      88 and a number of randomly derivatized water-soluble sulphated dextrans.

PMID- 19843095
TI  - Evidence that nitric oxide inhibits vascular inflammation and superoxide
      production via a p47phox-dependent mechanism in mice.
AB  - 1. Regulation of vascular Nox2-containing NADPH oxidase by p47(phox) plays a
      pivotal role in the development of atherosclerotic lesions through the generation
      of superoxide. Reduced vascular nitric oxide (NO) bioavailability is a major
      contributing factor in the initiation of atherosclerosis because it leads to an
      increase in adhesion molecule expression for inflammatory cell recruitment into
      the vessel wall. 2. The aim of the present study was to examine whether the anti
      oxidant and anti-inflammatory effects of endogenous NO involve inhibition of
      NADPH oxidase-dependent superoxide production. 3. To inhibit endogenous NO
      production, male C57Bl/6 wild-type (WT) mice or age-matched p47(phox-/-) mice
      were treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg per day
      for 4 weeks). Blood pressure was measured weekly via the tail-cuff method. Basal
      and phorbol dibutyrate (PDB)-stimulated aortic superoxide production was detected
      using lucigenin- and L-012-enhanced chemiluminescence, respectively. Aortic Nox2,
      p47(phox) and vascular cell adhesion molecule (VCAM)-1 expression were measured
      with western blotting. Plasma angiotensin (Ang) II levels were determined by
      radioimmunoassay. 4. Compared with vehicle (tap water)-treated WT mice (n = 4), L
      NAME-treated WT mice had significantly higher systolic blood pressure (SBP; n =
      6; P < 0.05) and basal and stimulated aortic extracellular superoxide production
      (n = 6-8; P < 0.05), but lower plasma AngII levels (P < 0.05). There was no
      change in Nox2 expression following l-NAME treatment of WT mice (n = 6); however,
      significant increases in both aortic p47(phox) (n = 6; P < 0.05) and VCAM-1
      expression (n = 6; P < 0.05) were observed. In p47(phox-/-) mice, l-NAME
      treatment significantly increased SBP (n = 3-4; P < 0.05), but failed to increase
      aortic superoxide production and VCAM-1 expression. 5. In conclusion, endogenous
      NO suppresses vascular inflammation, via inhibition of p47(phox) expression,
      leading to attenuation of NADPH oxidase-dependent superoxide production.

PMID- 19843096
TI  - Renin secretion and total body sodium: pathways of integrative control.
AB  - 1. Herein, we review mechanisms of sodium balance operating at constant mean
      arterial blood pressure (MABP); that is, under conditions where MABP does not
      provide the primary signal to the kidney. 2. Relative constancy of body fluids
      requires accurate regulation of total body sodium (TBS). Normally, plenty of
      sodium is ingested and balance is achieved by control of renal excretion driven
      by multiple central nervous, cardiovascular, endocrine and renal tubular
      mechanisms. Subtle changes in sodium balance are associated with parallel changes
      in extracellular volume (due to fast and precise osmoregulation), but not
      necessarily in MABP. Therefore, signals other than MABP seem to be the primary
      link between TBS and kidney function. 3. Renal functions involved in sodium
      homeostasis include: (i) the rate of glomerular filtration (GFR) determined by
      renal haemodynamics, including tubuloglomerular feedback (TGF); (ii) proximal
      tubular reabsorption involving glomerulotubular balance (GTB) and neurohumoral
      control; (iii) macula densa mechanisms influencing TGF and renin secretion; and
      (iv) distal tubular reabsorption dominated by the renin-angiotensin-aldosterone
      system (RAAS). 4. The present review focuses on the interactive, homeostatic
      operation of TBS, MABP, GTB, TGF and the RAAS. Regulation of sodium balance
      involves neurohumoral control of tubular sodium reabsorption, including proximal
      reabsorption. Central nervous system-mediated regulation of the latter modulates
      renin secretion. Homeostatically, the RAAS-TGF interaction seems analogous to a
      spring-shock absorber set-up: non-adaptive RAAS functions determine the new
      steady state position, whereas TGF controls the rate of change. Recruitment of
      renin-secreting cells during sustained stimulation may be essential for chronic
      adaptation, although details of this afferent arteriolar cell plasticity are
      unclear at present.

PMID- 19843099
TI  - Orchidectomy enhances the effects of phenylephrine in rat isolated portal vein.
AB  - 1. Orchidectomy results in long-term testosterone deprivation similar to that
      observed in male clinical pathologies, such as hypogonadism and age-related
      reductions in plasma testosterone concentrations. Although the vascular effects
      of these sorts of hormone deprivations are known in arteries, they have not been
      studied to the same extent in veins. 2. The aim of the present study was to
      determine the effect of orchidectomy, with or without subsequent testosterone
      replacement (started 23 days after orchidectomy; 10 mg/kg, i.m., testosterone
      propionate once every 5 days for 3 weeks), on responses of rat isolated portal
      veins and vena cavae to exogenous phenylephrine (PE). Isolated vessels were
      mounted in an organ bath and concentration-response curves constructed to PE (10(
      10)-10(-4) mol/L), endothelin (ET; 10(-10)-10(-5) mol/L) and KCl (10(-2)-1.2 x
      10(-1) mol/L; as a control). 3. Orchidectomy had no effect on contractile
      responses of either the portal vein or vena cava to KCl. However, orchidectomy
      enhanced the maximum response (R(max)) of the portal vein, but not the vena cava,
      to PE. Testosterone replacement had no effect on these responses. The effects of
      orchidectomy on the R(max) to PE in portal veins were not altered by the nitric
      oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (10(-4) mol/L) alone
      or combined with 10(-5) mol/L indomethacin (a non-selective cyclo-oxygenase
      inhibitor), but they were abolished following treatment of isolated vessels with
      the ET(A) and ET(B) receptor antagonists BQ-123 and BQ-788 (both at 10(-6)
      mol/L). Orchidectomy did not alter portal vein responses to the application of
      exogenous ET. 4. The results of the present study indicate that orchidectomy
      induced decreases in plasma testosterone can increase the venoconstrictor effects
      of PE on the portal vein and that this effect involves activation of both ET(A)
      and ET(B) receptors by locally produced ET.

PMID- 19843098
TI  - Inhibitory effect of fucoidan on nitric oxide production in lipopolysaccharide
      activated primary microglia.
AB  - 1. Microglial activation plays an important role in the pathogenesis of
      neurodegenerative diseases by producing various pro-inflammatory cytokines.
      Microglia-derived nitric oxide (NO) is critical for the lipopolysaccharide (LPS)
      induced selective loss of dopaminergic neurons. 2. Fucoidan is a sulphated
      polysaccharide extracted from brown seaweeds. It has a variety of biological
      actions, including anticoagulant, antiviral and anti-inflammatory effects. The
      aim of the present study was to investigate the effects of fucoidan on LPS
      induced cellular activation in microglia and to evaluate the inhibitory
      mechanisms involved. 3. To investigate the effects of fucoidan on LPS-induced
      cellular activation in microglia, primary microglial cells were preincubated with
      fucoidan (31.25, 62.5 and 125 microg/mL) for 10 min, followed by stimulation with
      LPS (0.01 microg/mL). Then, cell shape and NO production were determined 24 h
      after LPS stimulation, whereas inducible nitric oxide synthase (iNOS) mRNA and
      protein expression were determined at 6 and 18 h after LPS stimulation,
      respectively. To evaluate the inhibitory mechanisms involved, mitogen-activated
      protein kinase (MAPK) activation was also evaluated. 4. Lipopolysaccharide
      transformed cells into an amoeboid shape, whereas 62.5 microg/mL fucoidan
      inhibited this activation. Moreover, 125 microg/mL fucoidan significantly
      inhibited microglial NO production to 75% of that in LPS-treated group and also
      significantly diminished the expression of iNOS mRNA and protein by nearly 50%.
      Fucoidan (125 microg/mL) also suppressed phosphorylation of p38 and extracellular
      signal-regulated kinase (ERK) by approximately 50%, but not that of c-Jun N
      terminal kinase. 5. The results provide the first evidence that fucoidan has a
      potent inhibitory effect against LPS-induced NO production by microglia. The
      results also suggest that this inhibitory action of fucoidan involves suppression
      of p38 and ERK phosphorylation.

PMID- 19843097
TI  - Regulation of cardiac angiotensin-converting enzyme and angiotensin AT1 receptor
      gene expression in Npr1 gene-disrupted mice.
AB  - 1. Understanding of the regulatory mechanisms of gene expression in the control
      of blood pressure and fluid volume is a key issue in cardiovascular medicine.
      Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) signalling
      antagonizes the physiological and pathophysiological effects mediated by the
      renin-angiotensin-aldosterone system (RAAS) in the regulation of cardiovascular
      homeostasis. 2. The targeted-disruption of the Npr1 gene (coding for GC-A/PRA)
      leads to activation of the cardiac RAAS involved in the hypertrophic remodelling
      process, which influences cardiac size, expression of pro-inflammatory cytokine
      genes and the behaviour of various hypertrophy marker genes. The Npr1 gene
      knockout (Npr1(-/-)) mice exhibit 35-40 mmHg higher systolic blood pressure and a
      significantly greater heart weight to bodyweight ratio than wild-type (Npr1(+/+))
      mice. 3. The expression of both angiotensin-converting enzyme (ACE) and
      angiotensin II AT(1a) receptors are significantly increased in hearts from Npr1(
      /-) mice compared with hearts from Npr1(+/+) mice. In parallel, the expression of
      interleukin-6 and tumour necrosis factor-alpha is also markedly increased in
      hearts from Npr1(-/-) mice. 4. These findings indicate that disruption of
      NPRA/cGMP signalling leads to augmented expression of the cardiac RAAS in
      conjunction with pro-inflammatory cytokines in Npr1-null mutant mice, which
      promotes the development of cardiac hypertrophy and remodelling.

PMID- 19843100
TI  - Non-classic cystic fibrosis associated with D1152H CFTR mutation.
AB  - BACKGROUND: Limited knowledge exists on phenotypes associated with the D1152H
      cystic fibrosis transmembrane conductance regulator (CFTR) mutation. METHODS:
      Subjects with a D1152H allele in trans with another CFTR mutation were identified
      using the French Cystic Fibrosis Registry. Phenotypic characteristics were
      compared with those of pancreatic insufficient (PI) and pancreatic sufficient
      (PS) cystic fibrosis (CF) subjects in the Registry (CF cohort). RESULTS: Forty
      two subjects with D1152H alleles were identified. Features leading to diagnosis
      included chronic sinopulmonary disease (n = 25), congenital absence of the vas
      deferens (n = 11), systematic neonatal screening (n = 4), and genetic counseling
      (n = 2). Median age at diagnosis was 33 [interquartile range (IQR, 24-41)] years
      in D1152H subjects. Median sweat chloride concentrations were 43.5 (39-63) mmol/l
      in D1152H subjects and were markedly lower than in PI and PS CF subjects (p <
      0.05). Bronchiectasis was present in 67% of D1152H subjects, but Pseudomonas
      aeruginosa colonization and pancreatic insufficiency were present in <30% of
      subjects. Estimated rates of decline in forced expiratory volume in 1 s (FEV(1))
      were lower in D1152H subjects vs PI CF subjects (p < 0.05). None of the D1152H
      subjects identified since 1999 had died or required lung transplantation.
      CONCLUSIONS: When present in trans with a CF-causing mutation, D1152H causes
      significant pulmonary disease, but all subjects had prolonged survival.

PMID- 19843101
TI  - Mutation screening in patients for familial hypercholesterolaemia (ADH).

PMID- 19843102
TI  - Factors affecting survival and usefulness of implants placed in vascularized free
      composite grafts used in post-head and neck cancer reconstruction.
AB  - BACKGROUND: Bone-containing vascularized grafts have been used successfully to
      reconstruct post-cancer surgical defects. Dental implants can be placed in these
      bone-containing grafts to allow implant-supported prosthodontic reconstruction of
      these patients. PURPOSE: The aim of this study was to evaluate the survival of
      dental implants used in the rehabilitation of subjects treated with bone
      containing vascularized grafts to compare usability of implants placed at the
      time of reconstruction and after healing. MATERIALS AND METHODS: A cross
      sectional study was undertaken to examine survival rates of implants placed in
      vascularized bone-containing grafts either immediately at the time of surgical
      reconstruction or after 3 months healing. Other factors such as graft type,
      whether radiation therapy was given, and implant type were recorded. RESULTS: A
      total of 41 patients had 145 implants placed in 47 vascularized bone-containing
      flaps. Increased failure rate of implants was seen in immediately placed
      implants. There was also a significant increase in the number of osseointegrated
      implants that were prosthodontically unusable or sub-optimally placed in the
      immediate placement group. Radiation therapy was associated with a significant
      increase in failure rate. Modern implant surfaces appeared to perform better than
      machined/turned surfaces. Graft donor site did not influence implant survival.
      CONCLUSION: This study demonstrated the difficulties encountered with immediate
      placement of dental implants at the time of post-cancer reconstructive surgery.

PMID- 19843103
TI  - A clinical and histological case series study on calcium sulfate for maxillary
      sinus floor augmentation and delayed placement of dental implants.
AB  - BACKGROUND: Maxillary sinus floor augmentation is a procedure that is indicated
      in cases when the volume of the posterior maxillary bone is inadequate. The goal
      of this treatment is to obtain sufficient amount of bone tissue in order to gain
      osseointegration of endosseous implants. PURPOSE: The purpose of this study was
      to conduct a clinical and histological analysis of calcium sulfate (CaS) as bone
      graft substitute in sinus floor augmentation. MATERIAL AND METHODS: Ten patients
      with edentulous maxillas were included in this study. They had moderate to severe
      atrophy of the posterior maxilla. Surgiplaster (Classimplant(r), Rome, Italy) was
      used as graft material in the maxillary sinus and was covered by BioGide(r)
      (Geistlish Pharmaceutical, Wolhusen, Switzerland). After 4 months of graft
      healing, 40 dental implants were placed and a biopsy for histomorphometry was
      taken at these occasions. The specimens were viewed by light microscope, and the
      extent of bone regeneration and remaining graft material was evaluated.
      Radiographs were taken at the time of sinus augmentation and after 4 months of
      graft healing. RESULTS: At the time of abutment surgery, one implant was
      considered as a failure and was consequently removed, giving a survival rate of
      97.5% after 1 year of loading. Radiographs showed a mean of 26.5% shrinkage of
      the augmented area. A significant resorption of CaS was noted with a mean value
      of 8.8% of remaining graft material after 4 months of healing. The biopsies also
      revealed new bone formation with a mean value of 21.2% of the total biopsy area.
      Histology showed signs of an acellular substitution of CaS with bone-like tissue.
      CONCLUSION: The results of this study show that new bone regeneration occurs in
      the maxillary sinus after augmentation with CaS. This enabled successful
      placement, integration, and loading of dental implants in the posterior maxilla,
      as only 1 of 40 implants was lost during 1 year of follow-up.

PMID- 19843104
TI  - Long-term results of endosteal implants following radical oral cancer surgery
      with and without adjuvant radiation therapy.
AB  - PURPOSE: The aim of this study was to analyze the long-term survival of implants
      and implant-retained prostheses in patients after ablative surgery of oral cancer
      with or without adjunctive radiation therapy. MATERIALS AND METHODS: Between 1997
      and 2008, 66 patients who had undergone ablative tumor surgery in the oral cavity
      were treated with dental implants (n = 262). Thirty-four patients received
      radiation therapy in daily fractions of 2 Gy administered on 18 to 30 days.
      Implants were inserted in the maxilla (49; 18.7%) or mandible (213; 81.3%), in
      non-irradiated residual (65; 24.8%) or grafted bone (44; 16.8%) and in irradiated
      residual (15.6%) or grafted bone (39; 14.9%). Seventeen fixed protheses and 53
      removable dentures (34 bar attachments, 9 telescopic and 10 ball retained
      dentures) were inserted. RESULTS: Mean follow-up after implant insertion was
      47.99 (+/-34.31) months (range 12-140 months). The overall 1-, 5-, and 10-year
      survival rates of all implants were 96.6%, 96.6%, and 86.9%, respectively.
      Fourteen implants were lost in nine patients (5.3% of all implants); eight
      implants were primary losses, and five secondary losses because of an operation
      of tumor recurrence. There was no significantly lower implant survival for
      implants inserted into irradiated bone (p = .302), bone and/or soft-tissue grafts
      (p = .436), and maxilla or mandible (p = .563). All prosthetic restorations in
      patients without tumor recurrence could be maintained during the observation
      period. CONCLUSIONS: Implant survival is not significantly influenced by
      radiation therapy, grafts (bone and/or soft tissue), or location (maxilla or
      mandible). However, implants placed in irradiated bone exhibit a higher failure
      rate during the healing period than those placed in non-irradiated bone. No
      superstructure was particularly favorable. Osseointegrated implants can be used
      successfully in patients with prior history of ablative surgery with and without
      additional radiation therapy.

PMID- 19843105
TI  - Minimally invasive treatment for papillae deficiencies in the esthetic zone: a
      pilot study.
AB  - BACKGROUND: The presence of papillary deficiencies adjacent to dental implants or
      teeth presents an esthetic concern for the dental team and patients. PURPOSE: The
      aim of this pilot project is to evaluate a new method for reducing or eliminating
      small papillary deficiencies. The use of a commercially available gel was
      evaluated as a possible method for enhancing deficient papillae. MATERIALS AND
      METHODS: Eleven patients, seven females and four males, with an average age of
      55.8 years (ranging from 25 to 75 years) with 14 treated sites are included in
      this pilot study. Patients had a minimum of one papillary deficiency in the
      esthetic zone. Prior to treatment photographs were either taken at a 1:1 ratio or
      converted to a 1:1 ratio using a commercially available program. A
      standardization photographic device was not used. After administration of a local
      anesthetic, a 23-gauge needle was used to inject less than 0.2 mL of a
      commercially available and Food and Drug Administration-approved gel of
      hyaluronic acid 2-3 mm apical to the coronal tip of the involved papillae.
      Patients were seen every three weeks and treatment was repeated up to three
      times. Patients were followed from 6 to 25 months after initial gel application.
      A computer program measured changes in pixels between initial and final
      treatments. A formula was derived to determine percentage change in the negative
      space between initial and final examinations. RESULTS: Each site was individually
      evaluated. Three implant sites and one site adjacent to a tooth had 100%
      improvement between treatment examinations. Seven sites improved from 94 to 97%,
      three sites improved from 76 to 88%, and one site adjacent to an implant had 57%
      improvement. CONCLUSION: Results from this pilot study are encouraging and
      present evidence that small papillary deficiencies between implants and teeth can
      be enhanced by injection of a hyaluronic gel. Improvements were maintained for a
      range of 6 to 25 months.

PMID- 19843106
TI  - Radiographic features of mandibular trabecular bone structure in hypodontia.
AB  - PURPOSE: Radiographic parameters of mandibular trabecular bone structure between
      67 subjects having hypodontia and those without were studied on digital panoramic
      radiographs. MATERIALS AND METHODS: Three regions of interest (ROI) were defined:
      the ascending ramus, apical of the mandibular molar and mesial of the first
      mandibular molar. The effects of the presence of hypodontia and the ROI on the
      mandibular trabecular bone structure were tested for statistical significance by
      means of multivariate analysis. RESULTS: Radiographic parameters of trabecular
      bone architecture were found to differ between various regions of the mandible (p
      = 0.000), but not between the group of hypodontia subjects and their controls (p
      = 0.23). There was no interaction effect between the ROIs and the two groups (p =
      0.79). For people having hypodontia, some directional parameters of trabecular
      bone have a reverse correlation with the number of missing teeth. The fractal
      dimension and the number and perimeter of white segments in the binarized image
      correlate positively with the number of congenitally missing teeth. CONCLUSIONS:
      A limited number of parameters of radiographic mandibular trabecular bone
      structure correlate with the number of missing teeth. However, a markable
      difference in radiographic parameters of mandibular trabecular bone structure
      between hypodontia and non-hypodontia subjects could not be demonstrated.

PMID- 19843107
TI  - Sleeping implant in the temporal bone: report of a case with 20-year follow-up.
AB  - BACKGROUND: There is limited knowledge of the long-term fate of "sleeping" or
      nonloaded implants in the temporal bone. PURPOSE: This article describes the fate
      of a fixture installed in the temporal bone that remained unloaded for 20 years.
      PATIENT AND METHODS: A 25-year-old male with hemifacial microsomia had three
      osseointegrated implants installed for an auricular episthesis and bone-anchored
      hearing aid (BAHA) in the left temporal bone in 1988. Two of the implants for the
      ear episthesis were activated the same year, but the fixture for the hearing aid
      was not uncovered until 2008. When the patient experienced hearing problems at
      his office, he wanted to reactivate the sleeping implant. An audiogram showed a
      maximum conductive hearing loss with good preserved cochlear function. Before
      reactivation, an Accuitomo three-dimensional, cone beam computed tomography was
      performed. Resonance frequency analysis (RFA) using the Ostell technique was done
      when the implant was uncovered. RESULTS: Preoperative x-ray investigation showed
      the sleeping implant to be well integrated in the temporal bone, covered with 1
      mm bone, and with no signs of resorption. Geometric measurements correlating to
      the two loaded implants showed the sleeping implant to be positioned too close to
      these to be able to anchor a BAHA without interference with the episthesis.
      Surgical exploration was done to analyze the implant. The clinical status
      correlated well to that diagnosed from the x-ray investigation. RFA revealed the
      implant to be well integrated. A new fixture and abutment for BAHA was installed
      in the temporal line and activated 2 months after surgery. The patient is today
      supplied with a BAHA. CONCLUSION: It seems possible to use sleeping implants in
      the temporal bone even 20 years after installation.

PMID- 19843108
TI  - The peri-implantitis: implant surfaces, microstructure, and physicochemical
      aspects.
AB  - There are two ways of looking at secondary failures of osseointegration; one is
      to reflect on possible causes for the failure, the other focuses on the pathology
      per se. In the first case, background factors such as mechanical trauma (adverse
      loading) or inflammations/infections are being discussed as the cause of failure.
      Then peri-implantitis is a term reserved for implant disturbance due to
      inflammation/infections only. However, irrespective of the original reason for
      the failure being adverse loading or inflammation/infection, the end result with
      bone resorption and inflammation may be very similar. Hence, in the present
      article, an alternative outlook has been chosen. Trigerring factors for peri
      implantitis are generally gathered under four categories: lesions of peri-implant
      attachment, presence of aggressive bacteria, excessive mechanical stress, and
      corrosion. If only one of these factors would start a chain reaction leading to
      lesions, then the other factors may combine to worsen the condition. With other
      words, peri-implantitis is a general term dependent on a synergy of several
      factors, irrespective of the precise reason for first triggering off symptoms.

PMID- 19843109
TI  - Gender bias in Iranian living kidney transplantation program: a national report.
AB  - INTRODUCTION: Strong challenges exist about living kidney transplantation
      practices worldwide. One of these concerns is based on the observation that in
      many places women constitute the majority of living kidney donors but the
      minority of recipients. We studied this issue in Iran by using national data for
      kidney transplantation. METHODS: Data of the Iranian national registry for kidney
      transplantation which comprises data of all renal transplantations performed in
      the country during a 22 yr period were included in the study. Data of 16,672
      living donors (living related [LR]=16%, living unrelated [LUR]=86%) were
      analyzed. RESULTS: Males received 62.2% of all kidney transplants. From 16,672
      living donors, 20% and 80% were women and men, respectively. Recipients were more
      likely to receive kidney allograft from their own gender groups (p<0.05). In
      living related donations, mothers, brothers and sons were significantly more
      often donors than their counterparts of opposite gender. CONCLUSION: In contrast
      with previous reports from other countries, this study of Iranian national data
      revealed that in Iran, most related and unrelated living kidney donors are male
      and the percentage of recipients who are female exceeds the percentage of donors
      who are female. Considering previous reports from other countries, our findings
      suggest that Iran is the only country in which females are more likely to be
      recipients of a kidney allograft than donors. The reason for the predominance of
      male kidney donors in Iran is probably multifactorial and associated with
      economical, social and cultural issues. The financial incentives paid to living
      unrelated donors may be an attraction for males to donate a kidney although, even
      in living related donations, males constitute the majority of donors.

PMID- 19843110
TI  - Two-stage liver transplantation: an effective procedure in urgent conditions.
AB  - Temporary portocaval shunt and total hepatectomy is a technique used in the
      presence of toxic liver syndrome because of fulminant hepatic failure, hepatic
      trauma, primary non-function (PNF), and eclampsia. We performed this technique on
      four patients. An indication for anhepatic state was severe hemodynamic
      instability in three of them. Etiologies of these three patients were as follows:
      PNF after liver transplantation, ischemic hepatitis after right hepatic artery
      embolization, and massive reperfusion syndrome during a liver transplantation. In
      the fourth patient, during the liver transplantation when hepatic artery was
      ligated, a kidney carcinoma in the donor graft was discovered. We decided to
      complete the hepatectomy and to construct a temporary portocaval shunt. Mean
      anhepatic phases were 19 h and 15 min. All patients survived the two-stage liver
      transplantation procedure without major complications. Our cases demonstrated
      that temporary portocaval shunt while awaiting urgent liver transplantation could
      be an effective "bridge" in selected patients who develop toxic liver syndrome;
      however, a short time between portocaval shunt and transplantation and careful
      intensive care managements are mandatory.

PMID- 19843111
TI  - Massive ascites after living donor liver transplantation with a right lobe graft
      larger than 0.8% of the recipient's body weight.
AB  - BACKGROUND: There are only limited data on post-transplant ascites unrelated to
      small-sized grafts in living donor liver transplantation (LDLT). METHODS: The
      subjects were 59 adult patients who had received right lobe LDLT with a graft
      weight-to-recipient weight ratio (GRWR)>0.8%. Patients were divided into either
      Group 1 (n=14, massive ascites, defined as the production of ascitic fluid>1000
      mL/d that lasted longer than 14 d after LDLT) or Group 2 (n=45, no development of
      massive ascites). Patients were followed for a median period of 3.0 yr (range,
      0.5-7.5 yr). RESULTS: Group 1 had both higher Model for End-Stage Liver Disease
      score and Child-Pugh score than Group 2. Portal venous flow volume just after
      reperfusion was significantly greater in Group 1 than Group 2 (307.8+/-268.8 vs.
      176.2+/-75.0 mL/min/100 g graft weight, respectively; p<0.05). Post-transplant
      infectious complications including ascites infection developed more frequently
      within the first post-transplant month in Group 1. Massive ascites was
      significantly associated with early graft loss (p<0.05). CONCLUSION: Post
      transplant massive ascites associated with portal over-perfusion into the graft
      liver can develop in patients with a GRWR over 0.8%. Recipients with post
      transplant massive ascites require careful management to prevent infection.

PMID- 19843112
TI  - Faecal incontinence and depression: cause or effect?

PMID- 19843113
TI  - The role of reprogramming in sacral nerve modulation for faecal incontinence.
AB  - AIM: After implantation of a sacral nerve modulation (SNM) device for faecal
      incontinence (FI), patients are subjected to a rigid follow-up schedule. If
      symptoms recur, it may be necessary to reprogramme the stimulation parameters of
      the device. The aims of this study was to assess the need for reprogramming in
      patients with an SNM implant for FI. METHOD: All patients who received a
      permanent SNM implant for FI from January 2000 to February 2008 were included in
      this study. Patients were subjected to a rigid follow-up schedule at 1, 3, 6 and
      12 months, and yearly thereafter. Stimulator settings of the SNM device and
      changes made at every visit were collected and added to the database, and the
      number of patients in whom the stimulation parameter settings needed
      reprogramming was determined. RESULTS: A total of 155 patients (11 men) were
      analysed. The mean age (+/- standard deviation) of the patients was 57.7 +/- 11.9
      years. Median follow-up was 28.1 (range: 1.0-93.6) months. The mean voltage
      increased significantly from 1.8 V at 1 month to 2.0 V at 3 months. Thirty-nine
      (25.2%) patients required no reprogramming of their SNM implant during any of
      their follow-up visits; however, 51 (32.9%) patients required reprogramming at 1
      25% of their visits, 42 (27.1%) patients at 26-50% of their visits, 14 (9.0%)
      patients at 51-75% of their visits and nine (5.8%) patients at 76-100% of their
      visits. CONCLUSION: Physicians and patients need to be aware of the fact that
      reprogramming of the SNM stimulator needs to be carried out at least once during
      follow-up in the majority of patients. Trained physicians or specialist nurses
      are imperative to ensure effective follow-up and appropriate SNM reprogramming.

PMID- 19843114
TI  - Complications of transanal endoscopic microsurgery (TEMS): a prospective audit.
AB  - BACKGROUND: The aim of this study was to determine the postoperative
      complications of Transanal Endoscopic Microsurgery (TEMS) excision of rectal
      lesions. METHOD: A prospective audit of 262 consecutive TEMS procedures performed
      by a single surgeon between 1999 and 2008. RESULTS: The mean age of patients was
      72 years. The mean area of the lesions excised was 17.5 cm(2) with a mean
      diameter of 4.5 cm at a mean distance of 7.4 cm from the dentate line. There were
      201 full thickness excisions, 51 partial thickness excisions and nine were mixed
      or unclassified. Thirty-three (13%) patients developed 41 complications. There
      were two (0.8%) deaths within 30 days. Pelvic sepsis occurred in seven (3%)
      patients and was significantly more common after excision of low lesions within 2
      cm of the dentate line. Postoperative haemorrhage occurred in seven (3%) patients
      and was significantly less common when dissection was performed with ultrasonic
      dissection than with diathermy. Fourteen (5%) patients developed acute urinary
      retention. Four (1.5%) patients developed rectal stenosis and four (1.5%)
      suffered uncomplicated surgical emphysema that required no treatment.
      CONCLUSIONS: Transanal endoscopic microsurgery is a safe operation with a low
      mortality and morbidity. Pelvic sepsis is more common after excision of lesions
      within 2 cm of the dentate line. Ultrasonic dissection is associated with less
      postoperative haemorrhage than diathermy.

PMID- 19843115
TI  - Short disease-free interval is a significant risk factor for intrapulmonary
      recurrence after resection of pulmonary metastases in colorectal cancer.
AB  - OBJECTIVE: Surgical resection has been the first choice of treatment for
      resectable pulmonary metastases from colorectal cancer. However, early
      intrapulmonary recurrence is often observed and appropriate assessment of
      prognostic factors is controversial. The aim of this study was to define the
      factors affecting survival and intrapulmonary recurrence after surgical treatment
      of metastatic pulmonary tumours from colorectal cancer. METHOD: A retrospective
      analysis was performed of 56 consecutive patients who underwent pulmonary
      resection for colorectal metastases with a focus on prognostic factors and risk
      factors for intrapulmonary recurrence. RESULTS: The overall 5-year survival rate
      was 48.2%. In a univariate analysis, a short disease-free interval (DFI),
      multiple pulmonary metastases and abnormal prethoracotomy carcinoembryonic
      antigen (CEA) levels were poor prognostic factors. In a multivariate analysis, a
      short DFI and abnormal prethoracotomy CEA levels were independent prognostic
      factors. Twenty-two (39.3%) of the 56 patients had recurrences in the remnant
      lung after resection for pulmonary metastases, and 8 (36.4%) of these 22 patients
      underwent repeated pulmonary resections. The median DFI between first and second
      lung metastasis was 13 months. Univariate analyses revealed that multiple and
      bilateral lung metastases were risk factors for intrapulmonary recurrence. There
      was also a strong correlation between the DFI for intrapulmonary recurrence after
      the first pulmonary resection and the DFI for first pulmonary metastases.
      CONCLUSIONS: A short DFI was a risk factor for early tumour recurrence after
      resection for pulmonary metastases. The DFI might reflect oncological
      characteristics such as the tumour doubling time in colorectal cancer.

PMID- 19843116
TI  - Downstaging of colorectal cancer by the National Bowel Cancer Screening programme
      in England: first round data from the first centre.
AB  - OBJECTIVE: Data from randomized controlled trials of Colorectal Cancer (CRC)
      screening in Nottingham, UK and Funen, Denmark and pilot data from the English
      and Scottish arms of the National Bowel Cancer Screening Programme (NBCSP) have
      demonstrated predominantly early-stage disease amongst the screened population.
      The aim of this study was to investigate whether downstaging of cancers occurred
      in the NBCSP in Wolverhampton. METHOD: A case-control study was performed to
      compare the staging of CRC diagnosed in the NBCSP-screened population during the
      prevalent round (2 years) of screening, with cancers diagnosed prior to the
      introduction of the NBCSP. RESULTS: The total population in the screening area is
      899 000. A total of 108 346 FOB kits were sent out of which 55 931 were returned
      (51.6% uptake), A total of 1039 colonoscopies were performed with a 94.75%
      unadjusted caecal intubation rate. There were three complications (haemorrhages
      3) and no perforations. The NBCSP in Wolverhampton identified 106 (75% male) CRC
      in the first 2 years with 45.3% Dukes A, 21.7% B, 29.2% C and 3.8% D. Two hundred
      and fifty-six (61% male) CRC were identified in the control group, 10.1% Dukes A,
      50.0% B, 36.3% C and 3.5% D. There was a highly significant shift towards earlier
      stage disease in the screened group (P < 0.0001). CONCLUSION: The 2-year data
      from the first English centre to start bowel cancer screening demonstrates
      significant downstaging of cancer, consistent with both the RCT and pilot data.

PMID- 19843117
TI  - Fissurectomy and anal advancement flap for anterior chronic anal fissure without
      hypertonia of the internal anal sphincter in females.
AB  - AIM: Lateral internal sphincterotomy is considered the surgical treatment of
      choice for chronic anal fissure after failure of medical therapy but it risks
      continence. The aim of the study was to evaluate fissurectomy with advancement
      flap for anterior chronic anal fissure (CAAF) resistant to medical therapy.
      METHOD: Sixteen women with CAAF without hypertonia of the internal anal
      sphincter, unresponsive to previous medical treatment, were included in the
      study. Absence of hypertonia was defined as a maximum anal resting pressure (MRP)
      of less than 85 mmHg. All patients underwent fissurectomy with an advancement
      skin flap. RESULTS: Complete healing occurred in all patients within 30 days. The
      intensity and the duration of pain after defecation reduced from the first
      postoperative defecation. MRP before surgery and at 6 months showed no
      significant difference. At 1 month, four patients experienced a continence
      disturbance, two of whom had it preoperatively. At 12 months, two (12.5%)
      patients continued to experience a continence disturbance. CONCLUSION:
      Fissurectomy with skin advancement flap resulted in complete healing and full
      relief of symptoms in all patients. There was a low incidence of continence
      disturbance.

PMID- 19843118
TI  - Treatment of slow-transit constipation with sacral nerve modulation.
AB  - AIM: Constipation is common and a selection of the best treatment is difficult,
      especially for slow-transit constipation (STC). The aim of the study was to
      assess the effect of sacral nerve modulation (SNM) on STC. METHOD: A
      retrospective analysis of patients with STC, treated with SNM was undertaken. All
      were evaluated by cinedefecography, colon transit-time, Cleveland Clinic
      Constipation Score (CCS), SF-36 Quality of Life (QoL) and a bowel diary.
      Initially, all patients underwent a temporary implant for 4 weeks. The criteria
      of success were disappearance of necessity for laxatives or enema requirement,
      and improvement in QoL. RESULTS: Fifteen patients with STC were treated from
      March 2003 to May 2006. Nine (60%) underwent permanent implantation. After SNM,
      the mean improvement of Wexner Constipation Score (CCS) and QoL was 10 and 6.2
      respectively. There were no complications. The mean follow-up period was 42
      months. CONCLUSION: Sacral nerve modulation seems to be a useful option for STC.

PMID- 19843119
TI  - Sacral nerve stimulation for the treatment of faecal incontinence following low
      anterior resection for rectal cancer.
AB  - AIM: The aim of this study was to assess the effectiveness of sacral nerve
      stimulation (SNS) in the management of faecal incontinence following neoadjuvant
      therapy and low anterior resection (LAR) for rectal cancer. METHOD: In a
      prospective single-centre study, 15 patients (12 men, median age 72 years) were
      enrolled between 2005 and 2008. All had severe incontinence after total
      mesorectal excision, and 14 had received preoperative full-course
      chemoradiotherapy. The patients were followed up for a median of 50 (range: 24
      144) months. There was no recurrence (local or distal). Incontinence was
      evaluated using the Cleveland Clinic Florida Fecal Incontinence (CCF-FI) scoring
      system. Quality of life (QoL) was evaluated using the Fecal Incontinence Quality
      of Life (FIQL) questionnaire. SNS was performed in three stages. RESULTS: During
      percutaneous nerve evaluation (PNE), a good response was observed in seven
      patients, all of whom received a permanent implant. The median follow up was 12
      (range: 1-44) months. The mean CCF-FI score was reduced from 19.2 [standard
      deviation (SD) 1.2] to 6.2 (SD 1.7) (P < 0.01). The mean number of days per week
      with an incontinent episode decreased from 7 (SD 0) to 0.2 (SD 0.3) (P < 0.01),
      and the mean number of defaecations per week decreased from 42.5 (SD 13.7) to
      13.2 (SD 7.4) (P < 0.01). In the five patients with a permanent implant who were
      followed up for longer than 6 months, all FIQL scores improved. An increase in
      the mean resting and squeeze pressures was seen in four patients with a permanent
      implant. CONCLUSIONS: SNS is a treatment option for faecal incontinence after LAR
      for rectal cancer.

PMID- 19843121
TI  - Collaborative planning fosters multiple-benefit restoration projects on the
      Sacramento River.

PMID- 19843122
TI  - Ecosystem services as a stakeholder-driven concept for conservation science.

PMID- 19843123
TI  - Influence of a threatened-species focus on conservation planning.
AB  - Conservation efforts at local, regional, and global scales often focus on
      threatened species despite recent calls to adopt more equitable and potentially
      more economically rational approaches. Critics contend that conservation planning
      centered only on threatened species fails to deliver cost-efficient conservation
      outcomes. We explored how planning to preserve threatened mammal species would
      influence the efficiency and effectiveness of conservation investments in East
      Kalimantan, Indonesia. We found that the explicit protection of threatened
      species delivered cost-efficient outcomes in this situation, afforded adequate
      protection to over 90% of those species not yet considered endangered, and
      contributed to the partial protection of the remainder. We used Marxan, a
      conservation planning tool, to determine the frequency that planning units are
      selected in efficient reserve systems and assessed the relative risk of
      deforestation of each planning unit. Our methods allowed us to identify areas of
      the region that require the most urgent conservation action.

PMID- 19843124
TI  - Effects of harvest of nontimber forest products and ecological differences
      between sites on the demography of African mahogany.
AB  - The demographic impacts of harvesting nontimber forest products (NTFP) have been
      increasingly studied because of reports of potentially unsustainable harvest.
      Nevertheless, our understanding of how plant demographic response to harvest is
      altered by variation in ecological conditions, which is critical for developing
      realistic sustainable-use plans, is limited. We built matrix population models to
      test whether and how variation in ecological conditions affects population
      responses to harvest. In particular, we examined the effect of bark and foliage
      harvest on the demography of populations of African mahogany (Khaya senegalensis)
      in two contrasting ecological regions of Benin, West Africa. K. senegalensis bark
      and foliage harvest significantly reduced its stochastic population growth rates,
      but ecological differences between regions had a greater effect on population
      growth rates than did harvest. The effect of harvest on population growth rates
      (Deltalambda) was slightly stronger in the moist than in the drier region. Life
      table response experiments revealed that the mechanism by which harvesting
      reduced lambda differed between ecological regions. Lowered stasis (persistence)
      of larger life stages lead to a reduction in lambda in the drier region, whereas
      lowered growth of all life stages lowered lambda in moist region. Potential
      strategies to increase population growth rates should include decreasing the
      proportion of individuals harvested, promoting harvester-owned plantations of
      African mahogany, and increasing survival and growth by promoting no-fire zones
      in gallery forests. Our results show how population responses to harvest of NTFP
      may be altered by ecological differences across sites and emphasize the
      importance of monitoring populations over the climatic range in which they occur
      to develop more realistic recommendations for conservation.

PMID- 19843125
TI  - Devising appropriate policies and instruments in support of private conservation
      areas: lessons learned from the Klein Karoo, South Africa.
AB  - The amount of privately conserved land is increasing worldwide. The potential of
      these areas to contribute to the global conservation of biodiversity is
      significant, given that statutory protected areas alone will not suffice.
      Nevertheless, there is still inadequate support for private conservation areas,
      and further research on appropriate, flexible, and generally applicable incentive
      measures is necessary. We conducted 25 semistructured interviews with the owners
      of private conservation areas in the Little Karoo, South Africa, to examine
      landowner opinions of existing conservation policies and their relationships with
      the local conservation authority. We also assessed landowner preferences
      regarding conservation incentive measures. Landowners doubted the conservation
      authority's capacity to implement its stewardship program and were also
      discouraged by the bureaucracy of the program. The conservation authority was
      often viewed negatively, except where landowners had experienced personal contact
      from conservation staff or where strong social capital had formed among
      landowners. Landowners did not desire financial rewards for their conservation
      efforts, but sought recognition of their stewardship role and greater involvement
      from the conservation authority through personal contact. We conclude that
      conservation policies for private lands could benefit from the provision of
      extension services to landowners, promotion of formation of groups of landowners
      and other stakeholders, and public acknowledgment of the contributions private
      conservation areas make.

PMID- 19843126
TI  - Revisiting extinction in national parks: mountain caribou in Banff.

PMID- 19843127
TI  - Invest in opportunity, not inventory of hotspots.

PMID- 19843128
TI  - Consistent ecological selectivity through time in Pacific Island avian
      extinctions.
AB  - Understanding the ecological mechanisms that lead to extinction is a central goal
      of conservation. Can understanding ancient avian extinctions help to predict
      extinction risk in modern birds? I used classification trees trained on both
      paleoecological and historical data from islands across the Pacific to determine
      the ecological traits associated with extinction risk. Intrinsic traits,
      including endemism, large body size, and certain feeding guilds, were tightly
      linked with avian extinction over the past 3500 years. Species ecology and
      phylogeny were better predictors of extinction risk through time than extrinsic
      or abiotic factors. Although human impacts on birds and their habitats have
      changed over time, modern endangered birds share many of the same ecological
      characteristics as victims of previous extinction waves. My use of detailed
      predictions of extinction risk to identify species potentially in need of
      conservation attention demonstrates the utility of paleoecological knowledge for
      modern conservation biology.

PMID- 19843129
TI  - Effectiveness of marine protected areas in the Philippines for biodiversity
      conservation.
AB  - Quantifying the extent to which existing reserves meet conservation objectives
      and identifying gaps in coverage are vital to developing systematic protected
      area networks. Despite widespread recognition of the Philippines as a global
      priority for marine conservation, limited work has been undertaken to evaluate
      the conservation effectiveness of existing marine protected areas (MPAs). Targets
      for MPA coverage in the Philippines have been specified in the 1998 Fisheries
      Code legislation, which calls for 15% of coastal municipal waters (within 15 km
      of the coastline) to be protected within no-take MPAs, and the Philippine Marine
      Sanctuary Strategy (2004), which aims to protect 10% of coral reef area in no
      take MPAs by 2020. We used a newly compiled database of nearly 1000 MPAs to
      measure progress toward these targets. We evaluated conservation effectiveness of
      MPAs in two ways. First, we determined the degree to which marine bioregions and
      conservation priority areas are represented within existing MPAs. Second, we
      assessed the size and spacing patterns of reserves in terms of best-practice
      recommendations. We found that the current extent and distribution of MPAs does
      not adequately represent biodiversity. At present just 0.5% of municipal waters
      and 2.7-3.4% of coral reef area in the Philippines are protected in no-take MPAs.
      Moreover, 85% of no-take area is in just two sites; 90% of MPAs are <1 km(2).
      Nevertheless, distances between existing MPAs should ensure larval connectivity
      between them, providing opportunities to develop regional-scale MPA networks.
      Despite the considerable success of community-based approaches to MPA
      implementation in the Philippines, this strategy will not be sufficient to meet
      conservation targets, even under a best-case scenario for future MPA
      establishment. We recommend that implementation of community-based MPAs be
      supplemented by designation of additional large no-take areas specifically
      located to address conservation targets.

PMID- 19843130
TI  - Knowledge of the management of paediatric dental traumas by non-dental
      professionals in emergency rooms in South Araucania, Temuco, Chile.
AB  - AIM: The objective of this study was to investigate the level of knowledge and
      attitudes regarding first aid for dental trauma in children (TDI) by non-dental
      professionals and paramedical technicians of hospital emergency rooms in the
      South Araucania Health Service, Chile, which was attained through application of
      a survey. MATERIALS AND METHODS: Samples were collected from people with
      occupations in the respective emergency rooms. The participants were 82 people
      that were interviewed using a questionnaire regarding management of dental
      trauma. Paramedic technicians, general and specialist doctors, and nurses were
      included in this survey. The appraisal covered diverse aspects: birth date, age,
      sex, years of experience in the emergency room, and questions regarding specific
      dental trauma topics, which focused on crown fractures, luxation injuries in
      permanent dentition, avulsion in primary and permanent teeth, and the respective
      emergency treatments. RESULTS: Of the participants, 78.1% reported to have been
      presented with a TDI patient. The majority (90.2%) had not received formal
      training on TDI. These results revealed a wide distribution of responses. The
      overall dental trauma knowledge among the participants was relatively poor. For
      crown fractures management 54.9% indicated that they would ask the affected child
      about the crown remnants. In regard to transport and storage medium of avulsed
      permanent teeth, only 9.8% of the participants answered correctly and 43.9% of
      respondents stated that they would not replant an avulsed permanent tooth, since
      that procedure is considered the responsibility of a dentist. CONCLUSIONS: The
      majority of the respondents were not knowledgeable regarding TDI or the
      management and benefits of timely care, particularly in cases of avulsed
      permanent teeth. Therefore, formal education and training on the topic is
      suggested during undergraduate studies.

PMID- 19843131
TI  - Comparison of intraoral radiography and limited cone beam computed tomography for
      the assessment of root-fractured permanent teeth.
AB  - AIM: To compare intraoral occlusal (OC) and periapical (PA) radiographs vs.
      limited cone beam computed tomography (CBCT) in diagnosing root-fractured
      permanent teeth. MATERIAL AND METHODS: In 38 patients (mean age 24 years, range 8
      52 years) with 44 permanent teeth with horizontal root fractures, intraoral
      radiographs (PA and OC) and limited CBCT were used to evaluate the location
      (apical, middle, cervical third of the root) and angulation of the fracture line.
      Furthermore, the conventional radiographs and CBCT images were compared for
      concordance of fracture location. RESULTS: In the PA and OC radiographs, 28
      fractures (63.6%) were located in the middle third of the root, 11 (25.0%) in the
      apical third and 5 (11.4%) in the cervical third. The PA/OC radiographs and the
      sagittal CBCT images (facial aspect) yielded the same level of root fracture in
      70.5% of cases (31 teeth; 95% CI: 54.1-82.7%). The PA/OC radiographs and sagittal
      CBCT images (palatal aspect) showed the same level of root fracture in 31.8% of
      cases. There was a statistically significant association between the angle at
      which the root fracture line intersected the axis of the tooth and the level of
      root fracture in the facial aspect of the sagittal CBCT images. CONCLUSIONS: The
      diagnosis of the location and angulation of root fractures based on limited CBCT
      imaging differs significantly from diagnostic procedures based on intraoral
      radiographs (PA/OC) alone. The clinical significance for treatment strategies and
      for the prognosis of root-fractured teeth has to be addressed in future studies.

PMID- 19843132
TI  - Prevalence of maxillofacial injuries by motorized two wheeler road traffic
      accidents in Bangalore city.
AB  - INTRODUCTION: Two wheeler users in India are the most vulnerable for road
      fatalities and two wheelers constitute the major portion of vehicular traffic.
      OBJECTIVES: To assess the prevalence of maxillofacial injuries among the victims
      of motorized two wheeler road traffic accidents in Bangalore city. MATERIALS AND
      METHODS: Medical records of cases reported during January 2006-June 2007 to
      hospitals were considered and data regarding age, sex, date of trauma, rider or
      pillion rider, alcohol consumption, site of injury on the face and associated
      injuries to other parts of the body were recorded. RESULTS: The prevalence of
      injuries among males and females was in the ratio of 3:1. Most of them were in
      the age group of 21-30 years. Most of the cases were recorded on Saturdays
      (17.4%) and in the months of August (9%) and September (9.7%) and the least
      number of cases were reported in January, March and June (2.1%) of 2007. The
      decrease in number of cases coincides with the implementation of the Helmet Rule
      in the city. CONCLUSION: There is a need to stress on the importance of usage of
      helmets and adherence to traffic rules during the high-risk periods to reduce the
      incidence of road traffic accidents and accompanying maxillofacial injuries.

PMID- 19843133
TI  - Rationale for esthetic tissue preservation of a fresh extraction socket by an
      implant treatment concept simulating a tooth replantation.
AB  - In cases of an immediate insertion and loading of implants after a traumatic loss
      of the patient's own dentition or due to an inevitable extraction of an anterior
      tooth, it is essential to provide the patient with an adequate provisional crown.
      A soft-tissue recession must be avoided, whether it is due to a compression of
      the peri-implant soft-tissue caused by an over-dimensioned restoration in the
      cervical collar of the provisional crown or to a too small dimensioned sulcus
      former. A simulation of the exact dimension of the lost tooth - especially on the
      cervical part of the new provisional restoration - is expected to preserve all
      relevant information and allows the design of a naturally looking emergence
      profile. Based on theoretical considerations and a case report, the authors
      intend to demonstrate that a near-naturally dimensioned sealing of the dento
      gingival soft-tissue collar may initiate a tissue-maintaining healing process,
      similar to a tooth replantation. The natural dental crown, connected to an
      implant instead of the root, is applied for a tight sealing of the wound. If due
      to traumatic impact the tooth is no longer available, a naturally dimensioned
      crown restoration will serve as an alternative wound sealant.

PMID- 19843134
TI  - Unilateral coronoid hyperplasia following trauma: a case report.
AB  - This case describes surgical correction of unilateral coronoid hyperplasia in a
      13-year-old boy due to trauma. Treatment included coronoidectomy by intraoral
      approach after the diagnosis was confirmed. Computed tomography scan and
      occipitomental view radiograph were utilized for investigation. The resected
      coronoid process was sent for histopathological study. The histopathological
      examination revealed decalcified sections showing osteochondroid hyperplasia at
      the expanded end. On clinical and radiographic review at 2 years postoperation,
      the patient was well, completely symptom free and had improved mouth opening.
      This case report demonstrates the management of sports injury related unilateral
      coronoid hyperplasia. Emphasis was also placed on postoperational rehabilitation
      to prevent any relapse.

PMID- 19843135
TI  - Propolis inhibits osteoclast maturation.
AB  - Propolis, a natural product produced by the honey bee, has been successfully used
      in medicine as an anti-inflammatory and antimicrobial agent. Traumatic injuries
      to the teeth, especially avulsion injuries, present a challenging situation for
      the clinician because of post-treatment complications, such as inflammatory
      and/or replacement resorption. Agents that reduce osteoclast numbers and activity
      may be useful in the treatment of traumatic injuries to the teeth. In this study,
      we evaluated propolis as an anti-resorptive agent. Calcitriol-stimulated mouse
      marrow cultures, which contain both osteoclasts and osteoblasts, were exposed to
      the ethanol extracts of propolis or vehicle control and stained for tartrate
      resistant acid phosphatase (TRAP)-activity to identify osteoclasts. A
      significant, dose-dependent reduction in multinuclear TRAP+ cells was
      demonstrated, although the propolis treatment accommodated cell growth and
      survival (P < 0.05). Propolis also reduced the formation of actin rings in pure
      cultures of RAW 264.7 osteoclast-like cells, suggesting that it exerts direct
      actions on osteoclast maturation. In summary, our data suggest that propolis
      inhibits late stages of osteoclast maturation including fusion of osteoclasts
      precursors to form giant cells and formation of actin rings. This supports the
      hypothesis that it may prove useful as a medicament to reduce resorption
      associated with traumatic injuries to the teeth.

PMID- 19843136
TI  - The three-dimension finite element analysis of stress in posterior tooth residual
      root restored with postcore crown.
AB  - OBJECTIVE: Teeth that have been endodontically treated and restored with postcore
      crown may experience fracture sometimes. Some researchers have analyzed the
      stress of the anterior teeth after postcore crown restoration, but the stress of
      the posterior teeth after such restoration has not been reported. We used three
      dimension finite element methods to analyze the stress magnitude and distribution
      of remaining dentin in posterior tooth residual root restored with postcore
      crown. The binding material, loading direction, number, length and material of
      posts were studied. METHODS: The models of residual root of maxillary first molar
      restored with postcore crown were created by CT scanning, mimics software and
      abaqus software. Different number, length and material of posts were used in the
      modeling. The posts were cemented with zinc-phosphate cement or composited resin.
      A load of 240 N was applied to the occlusal surface in four directions and
      tensile, shear, and von Mises stresses were calculated. RESULT: (i) The maximum
      stress on remaining dentin changed irregularly as the number and length of posts
      changed. (ii) The maximum stress on remaining dentin decreased slightly as
      elastic modulus of the material of posts increased. (iii) The maximum stress on
      bonding layer and remaining dentin was lower when bonded with resin luting agent
      than with zinc-phosphate cement. (iv) The maximum stress on remaining dentin
      increased markedly as loading angle increased. CONCLUSION: The number, length,
      material of posts, bonding material and loading angle all have influence on the
      magnitude and distribution of stress. The influence of loading angle is most
      apparent.

PMID- 19843138
TI  - Cytopathological diagnosis of hyalinizing trabecular tumour, a rare thyroid
      neoplasm.

PMID- 19843137
TI  - Modified Papanicolaou staining protocol with minimum alcohol use: a cost-cutting
      measure for resource-limited settings.
AB  - OBJECTIVE: To devise a simple, cost-effective protocol for Papanicolaou (Pap)
      staining of cervicovaginal smears. METHODS: Five hundred coded paired cervical
      smears were collected from women as part of routine cervical cancer screening.
      One set of smears was stained by conventional Pap staining protocol (CP) and the
      other by a modified protocol (MP) in which alcohol was replaced by 1% acetic acid
      in all the steps except during fixation and prior to mounting; in addition, one
      alcohol-based counterstain, OG, was omitted. The smears were examined blindly by
      the pathologists and then decoded. Each pair of smears was compared and the two
      protocols were analysed for staining quality and diagnoses by McNemar and chi
      square tests. RESULTS: The staining quality in the MP was satisfactory. The
      nuclear and cytoplasmic features were comparable to the CP. Cytoplasmic
      transparency was maintained in the MP and the differential staining of blue/green
      and pink was acceptable to the pathologists and technicians. The diagnoses agreed
      in all cases and there was no compromise in interpreting the smears. With MP it
      took only 3-4 minutes to stain a batch of 50 slides. in contrast to the 20
      minutes taken by CP. The MP used almost one-seventh of the amount of alcohol
      compared with CP, which translated into a significant cost reduction per smear.
      CONCLUSIONS: The improvised Pap staining protocol with minimum alcohol use is a
      simple, cost-effective and technician-friendly procedure that can be easily
      adopted in high-volume, resource-limited laboratories for mass cervical cancer
      screening.

PMID- 19843139
TI  - An audit of liquid-based cervical cytology screening samples (ThinPrep and
      SurePath) reported as glandular neoplasia.
AB  - OBJECTIVES: The aims of this study were to assess the number of cases diagnosed
      as glandular neoplasia (national report code 6) of cervical (6A) and non-cervical
      (6B) types on ThinPrep (TP) and SurePath (SP) liquid-based cytology (LBC) samples
      and to calculate the positive predictive value (PPV) of these diagnoses for
      significant glandular and/or squamous pathology for local audit and as a
      contribution to national data on glandular neoplasia. METHODS: A computerized
      search identified all screening LBC samples reported as glandular neoplasia
      during the 24-month period from January 2006 to December 2007. Corresponding
      histology samples were identified, with a minimum follow-up period of 6 months
      for each case. RESULTS: A total of 70 samples, representing 70 patients, were
      reported as glandular neoplasia, 39 TP (55.7%) and 31 SP (44.3%), with 46 samples
      (31 TP, 15 SP) reported as 6A and 24 samples (eight TP, 16 SP) as 6B. PPV of
      glandular neoplasia was calculated for a biopsy diagnosis of cervical glandular
      intraepithelial neoplasia/adenocarcinoma and/or cervical intraepithelial
      neoplasia (CIN) 2 or worse. The PPV of 6A was 100% for both TP and SP. The PPV of
      6B for adenocarcinoma was 62.5% for TP and 66.7% for SP. The combined PPV for 6A
      + 6B was 92.3% for TP, 83.3% for SP and 88.4% combined. The overall pick-up rates
      for the two methods were significantly different (TP 0.031%, SP 0.052%; P =
      0.014). Histology showed only CIN3 with endocervical crypt involvement in nine TP
      cases and one SP case.

PMID- 19843140
TI  - Histoplasmosis: cytodiagnosis and review of literature with special emphasis on
      differential diagnosis on cytomorphology.
AB  - BACKGROUND: Human infection with Histoplasma capsulatum runs the gamut from
      asymptomatic to disseminated disease. In immunocompromised patients, a tiny
      inoculum can lead to widespread disseminated infection. Early diagnosis and
      initiation of treatment is therefore important. OBJECTIVE: To review the cases of
      histoplasmosis diagnosed on fine needle aspiration cytology (FNAC) and to discuss
      the clinical presentation, associated inflammatory response, load of organisms
      and differential diagnosis on cytomorphology in these cases. METHODS:
      Retrospective review of seven cases of histoplasmosis at a tertiary-care centre
      during the period from 1998 to 2009 was performed. Clinical presentation along
      with cytomorphological features were studied and discussed in detail. RESULTS:
      The mean age of patients was 48.6 years and six out of seven were male. History
      of immunodeficiency (HIV) was available in five cases. Six patients presented
      with peripheral and/or abdominal lymphadenopathy. One patient had nodular shadows
      in both lungs and two also had skin lesions. On cytological smears, a variable
      load of uniform round to oval, about 2-4 microm in diameter, budding yeasts were
      seen intracellularly (within histiocytes) as well as extracellularly. In one case
      (HIV positive), these organisms were also seen within neutrophil
      polymorphonuclear leucocytes. In two cases, an inflammatory response in the form
      of epithelioid cell granulomas along with multinucleated giant cells was seen.
      CONCLUSIONS: FNAC is a reliable tool to recognize infection with H. capsulatum in
      tissues. This infection can cause a variable inflammatory response, which should
      be considered while reporting on such cases.

PMID- 19843141
TI  - An audit of cervical cytology in HIV-positive women.
AB  - OBJECTIVE: To investigate whether a cohort of human immunodeficiency virus
      positive (HIV+) women were having annual cervical cytology as recommended by the
      English National Health Service cervical screening programme (NHSCSP) guidelines.
      METHODS: An audit of cervical cytology in an HIV+ cohort of 187 women by
      obtaining their last cervical cytology result and recall from local cytology
      services. RESULTS: Of the 187 women in the audit, two were ineligible, leaving
      185 women, 167 (90.3%) of whom were aged 25-64 years and eligible for screening.
      Of the 185 women, 126 (68.1%) had a cytology history, 50 (27%) had never had
      cervical cytology and nine (4.9%) had inadequate details to ascertain whether or
      not they had a cytology history. Of the 126 with a cytology record, 34 (27%) had
      a current cytological abnormality, which was low grade in 25 (19.8%) and high
      grade in nine (7.1%). Among women aged 25-64 years attending the clinic, these
      percentages were significantly higher than expected for England as a whole (P <
      0.001). Of 126 women with a cytology record, 29 (23%) were overdue for their
      recall date and of these the previous test was abnormal in 14 (48.3%). Cytology
      tests were taken within the community setting in 61 (48.4%), whereas 65 (51.6%)
      were seen either at an HIV sexual health clinic or were under colposcopy follow
      up. Of 91 women with negative cytology only 50 (54.9%) were recommended for
      repeat in 12 months. CONCLUSION: This audit demonstrates a high rate of
      cytological abnormalities among HIV+ women compared with the screening population
      at large. Implementation of NHSCSP guidelines has been difficult and requires
      improved care pathways between HIV clinics, primary care and laboratories.

PMID- 19843142
TI  - Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA): experience of an
      academic centre in the USA.
AB  - OBJECTIVES: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has
      become widely accepted as an effective modality for obtaining tissue for primary
      diagnosis and staging. We have been using EUS-FNA since July 2001 and herein we
      summarize our experience over a 5-year period. METHODS: A computer-based search
      for in-house EUS-FNA was performed in the pathology database from July 2001 to
      October 2006. To calculate the sensitivity, specificity and accuracy of EUS-FNA,
      the cytology diagnosis was compared with the surgical follow-up. RESULTS: A total
      of 951 EUS-FNAs were performed during the study period and included 279
      pancreatic solid lesions, 186 pancreatic cyst lesions, 249 lymph node
      aspirations, 111 gastrointestinal (GI) tract submucosal lesions, and 126
      miscellaneous lesions. EUS-FNA had a very high sensitivity and accuracy for solid
      pancreatic lesions (94.7 and 97.7%, respectively), low sensitivity and accuracy
      but high specificity (47, 64.8 and 95%, respectively) for cystic lesions. Cyst
      fluid carcinoembryonic (CEA) levels were significantly higher in mucinous
      neoplasms than non-neoplastic cysts. EUS-FNA also had very high sensitivity and
      specificity for detecting metastatic carcinoma in lymph nodes (95 and 100%,
      respectively). GI submucosal spindle cell tumours were further classified with
      immunohistochemical stains performed either on a cell block or a core biopsy
      obtained via EUS guidance. CONCLUSIONS: EUS-FNA has a very high sensitivity and
      accuracy for pancreatic solid lesions, but the sensitivity for cystic lesions is
      generally low. Cyst fluid chemical analysis for CEA is helpful, but the overlap
      between mucinous neoplasm and non-neoplastic cysts is significant. Recognizing GI
      contamination is important and immunohistochemical stains are useful for GI
      submucosal spindle cell lesions.

PMID- 19843143
TI  - Cell blocks allow reliable evaluation of expression of basal (CK5/6) and luminal
      (CK8/18) cytokeratins and smooth muscle actin (SMA) in breast carcinoma.
AB  - OBJECTIVE: Gene expression studies have revealed several molecular subtypes of
      breast carcinoma with distinct clinical and biological behaviours. DNA microarray
      studies correlated with immunohistochemical profiling of breast carcinomas using
      cytokeratin (CK) markers, Her2/neu, oestrogen receptor (ER), and basal
      myoepithelial cell markers have identified five breast tumour subtypes: (i)
      luminal A (ER+; Her2/neu-), (ii) luminal B (ER+; Her2/neu+), (iii) Her2
      overexpression (ER-; Her2/neu+), (iv) basal-like (ER-; Her2/neu-, CK5/6 and 14+),
      and (v) negative for all markers. Luminal carcinomas express cytokeratins in a
      luminal pattern (CK8/18), and the basal-like type expresses CK5/6 and CK14 or
      basal epithelial cell markers. CK5/6, CK8/18, and smooth muscle actin (SMA)
      expression were assessed in cell blocks and compared with expression in surgical
      specimens. METHODS: Sixty-two cases of breast carcinoma diagnosed by fine needle
      aspiration cytology with cell blocks and available surgical specimens were
      included. Cell blocks containing at least 10 high-power fields each with at least
      10 tumour cells and surgical specimens were immunostained for CK5/6, CK8/18 and
      SMA. RESULTS: Percentage sensitivity, specificity, positive predictive value,
      negative predictive value and accuracy were, respectively, 77, 100, 100, 92 and
      94 for CK5/6; 98, 66, 96, 80 and 95 for CK8/18; and 92, 96, 85, 98 and 95 for
      SMA. CONCLUSION: The identification of CK5/6, CK8/18 and SMA by
      immunohistochemistry in cell blocks can be a reliable method that yields results
      close to those obtained in surgical specimens, and can contribute to the
      classification of breast carcinomas with luminal and basal expression patterns,
      providing helpful information in the choice of treatment and in the evaluation of
      prognostic and predictive factors.

PMID- 19843144
TI  - Fine needle aspiration cytology in HIV-related lymphadenopathy: experience at a
      single centre in north India.
AB  - OBJECTIVE: Fine needle aspiration (FNA) is emerging as a rapid and minimally
      invasive tool in evaluating lymphadenopathy associated with human
      immunodeficiency virus (HIV). We evaluated the role of FNA in differentiating
      various causes of lymphadenopathy in patients with HIV and correlated the
      cytological diagnosis with CD4 counts. METHODS: Seventy-nine HIV-positive
      patients (median age 35 years, 68 male) underwent ultrasound-guided (n = 16) and
      unguided (n = 63) FNA from 1999 to 2006. Smears were stained with May-Grunwald
      Giemsa, haematoxylin & eosin and Papanicolaou stains. Ziehl-Neelsen (ZN) staining
      for acid-fast bacilli (AFB) was performed in all cases. Staining for fungus was
      performed whenever required. RESULTS: The aspirates were adequate in 75 cases
      (95%). Non-specific reactive hyperplasia was the most common FNA diagnosis (39,
      52%) followed by granulomatous necrotizing lymphadenitis (15, 20%), necrotizing
      lymphadenitis (13, 17.3%) and granulomatous lymphadenitis (4, 5.2%). Fungal
      infection and non-Hodgkin lymphoma (NHL) were seen in two patients each. ZN
      staining was positive for AFB in 25 (33.3%) cases. One of these was
      morphologically interpreted as reactive hyperplasia, 12 as necrotizing
      lymphadenitis and 12 as granulomatous necrotizing lymphadenitis. Both patients
      with NHL had CD4 counts below 100/dl. Necrotizing lymphadenitis and granulomatous
      lymphadenitis were significantly associated with CD4 counts below and above
      200/dl, respectively (P = 0.0002). CONCLUSIONS: FNA is an important tool for
      assessing the cause of lymphadenopathy in HIV patients. Necrotizing inflammation
      is more often seen in patients with low CD4 counts. AFB are commonly found in
      necrotic aspirates with or without granulomas. However, a stain for AFB should be
      performed in all aspirates from HIV-related lymphadenopathy including reactive
      hyperplasia.

PMID- 19843145
TI  - FNAC of nodular fasciitis mimicking a pleomorphic adenoma: another diagnostic
      pitfall.

PMID- 19843146
TI  - Fine needle aspiration cytology in a case of recurrent aggressive angiomyxoma of
      vulva.

PMID- 19843147
TI  - Pigmented black neuroendocrine tumour of the pancreas diagnosed by fine needle
      aspiration cytology.

PMID- 19843148
TI  - Fine needle aspiration cytology of oxyphilic parathyroid hyperplasia.

PMID- 19843149
TI  - Diagnosis of alveolar rhabdomyosarcoma in effusion cytology: a diagnostic
      pitfall.

PMID- 19843150
TI  - Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious
      epithelial cell death at lactation.
AB  - The family of Eph receptor tyrosine kinases and their membrane bound ligands, the
      ephrins, are involved in a wide variety of morphogenic processes during embryonic
      development and adult tissue homeostasis. Receptor-ligand interaction requires
      direct cell-cell contact and results in forward and reverse signaling originating
      from the receptor and ligand, respectively. We have previously shown that EphB4
      and ephrinB2 are differentially expressed during the development of the adult
      mammary parenchyma. Overexpression of EphB4 in the mammary epithelium of
      transgenic mice leads to perturbations in mammary epithelial morphology, motility
      and growth. To investigate the role of ephrinB2 signaling in mammary gland
      biology, we have established transgenic mice exhibiting conditional ephrinB2
      knockout in the mammary epithelium. In homozygote double transgenic CreLox mice,
      specific knockout of ephrinB2 occurred in the mammary epithelium during the first
      pregnancy-lactating period. Abolishing ephrinB2 function led to severe
      interference with the architecture and functioning of the mammary gland at
      lactation. The morphology of the transgenic lactating glands resembled that of
      involuting controls, with decreased epithelial cell number and collapsed lobulo
      alveolar structures. Accordingly, massive epithelial cell death and expression of
      involution-specific genes were observed. Interestingly, in parallel to cell
      death, significant cell proliferation was apparent, suggestive of tissue
      regeneration.

PMID- 19843151
TI  - Metamorphic pitx2 expression in the left habenula correlated with lateralization
      of eye-sidedness in flounder.
AB  - The bilateral symmetry of flounder larvae changes through the process of
      morphogenesis to produce external asymmetry at metamorphosis. The process is
      characterized by the lateral migration of one eye and pigmentation at the ocular
      side. Migration of the left or right eye to produce either dextral or sinistral
      forms, respectively, is usually fixed within a species. Here we propose a
      mechanism for the mediation of lateralization by the nodal-lefty-pitx2 (NLP)
      pathway in flounders, in which pitx2, the final left-right determinant of the NLP
      pathway, is re-expressed in the left habenula at pre-metamorphosis. After the
      initiation of left-sided pitx2 re-expression, the eye commences migration, when
      the habenulae shift their position on the ventral diencephalon rightwards in
      sinistral flounder (Paralichthys olivaceus) and leftwards in dextral flounder
      (Verasper variegatus). In addition, the right habenula increases in size relative
      to the left habenula in both species. Loss of pitx2 re-expression induces
      randomization of eye-sidedness, manifesting as normal, reversed or bilateral
      symmetry, with laterality of the structural asymmetry of habenulae being entirely
      inverted in reversed flounders compared with normal ones. Thus, flounder pitx2
      appears to be re-expressed in the left habenula at metamorphosis to direct eye
      sidedness by lateralizing the morphological asymmetry of the habenulae.

PMID- 19843152
TI  - Stem cell system in tissue regeneration in fish.
AB  - During evolution from single-cell to multi-cellular organisms, organisms
      developed the needed machinery by which a vast number of functionally different
      types of cells could be unified into an individual. To attain this goal,
      organisms evolved the developmental strategies that produced different cell types
      and unified them into complex body architecture. However, a more intriguing
      feature of multi-cellular organisms is that they can maintain their bodies
      throughout long life. For tissue maintenance, stem and/or progenitor cells in
      many tissues and organs are thought to play an important role; however, we know
      little about their control and the process of tissue reconstitution. As cells are
      fragile, all animals have the ability, more or less, to replace damaged or dead
      cells; however, there are large variations in such abilities, depending on the
      type of organs and the species. Though vertebrates cannot reconstitute their
      bodies from a small piece as do planarians, some lower vertebrates, unlike
      mammals, have the ability to regenerate body appendages and many internal organs.
      If we unveil the nature of stem cells in striking examples of such regeneration,
      this information can be applied to mammals and greatly benefit us. The focus in
      the present review is on the recent advances in our knowledge about the
      regeneration mechanism in fish, including the stem cells that are involved.

PMID- 19843153
TI  - Infrared laser-mediated local gene induction in medaka, zebrafish and Arabidopsis
      thaliana.
AB  - Heat shock promoters are powerful tools for the precise control of exogenous gene
      induction in living organisms. In addition to the temporal control of gene
      expression, the analysis of gene function can also require spatial restriction.
      Recently, we reported a new method for in vivo, single-cell gene induction using
      an infrared laser-evoked gene operator (IR-LEGO) system in living nematodes
      (Caenorhabditis elegans). It was demonstrated that infrared (IR) irradiation
      could induce gene expression in single cells without incurring cellular damage.
      Here, we report the application of IR-LEGO to the small fish, medaka (Japanese
      killifish; Oryzias latipes) and zebrafish (Danio rerio), and a higher plant
      (Arabidopsis thaliana). Using easily observable reporter genes, we successfully
      induced gene expression in various tissues in these living organisms. IR-LEGO has
      the potential to be a useful tool in extensive research fields for cell/tissue
      marking or targeted gene expression in local tissues of small fish and plants.

PMID- 19843154
TI  - Retinoic acid is a negative physiological regulator of N-cadherin during early
      avian heart morphogenesis.
AB  - The vitamin A-deficient (VAD) early avian embryo has a grossly abnormal
      cardiovascular system that is rescued by treating the embryo with the vitamin A
      active form, retinoic acid (RA). Here we examine the role of N-cadherin (N-cad)
      in RA-regulated early cardiovascular morphogenesis. N-cad mRNA and protein are
      expressed globally in the presomite through HH14 normal and VAD quail embryos.
      The expression in VAD embryos prior to HH10 is significantly higher than that in
      normal embryos. Functional analyses of the N-cad overproducing VAD embryos reveal
      N-cad involvement in the RA-regulated cardiovascular development and suggest that
      N-cad expression may be mediated by Msx1. We provide evidence that in the early
      avian embryo, endogenous RA is a negative physiological regulator of N-cad. We
      hypothesize that a critical endogenous level of N-cad is needed for normal early
      cardiovascular morphogenesis to occur and that this level is ensured by stage
      specific, developmentally regulated RA signaling.

PMID- 19843155
TI  - The Drooling Impact Scale: a measure of the impact of drooling in children with
      developmental disabilities.
AB  - AIM: To describe the development and clinimetric properties of a new scale to
      evaluate changes in the impact of drooling in children with developmental
      disabilities. METHOD: After examining the properties of potential items, 10 items
      were retained for inclusion in the final Drooling Impact Scale. The clinimetric
      properties of the scale were evaluated using data from two convenience samples of
      children attending a saliva-control clinic: a stable group (n=31, 22 males, nine
      females; mean age 10y 7mo, SD 4y 5mo, range 3y 6mo-18y 3mo; cerebral palsy [CP]
      n=17, intellectual disability n=10; non-ambulatory n=13, nonverbal n=12) and an
      intervention group (n=49, 29 males, 20 females; mean age 11y, SD 3y 6mo, range 3y
      4mo-16y 10mo; CP n=31, intellectual disability n=15; non-ambulatory n=27,
      nonverbal n=28). To assess validity, changes in scores on the Drooling Impact
      Scale over time were compared with a carer's global rating of change using
      Pearson's correlations and t-tests. A concordance correlation coefficient was
      used to compute the level of agreement between assessments 1 month apart in
      stable children. Effect size, standardized response mean, Guyatt responsiveness
      statistic, and an unpaired t-test were used to estimate responsiveness. RESULTS:
      The correlation between the global rating and change in Drooling Impact Scale
      scores was 0.69 (p<0.001). The concordance correlation coefficient was 0.85. An
      effect size of 1.8, standardized response mean of 1.5, Guyatt responsiveness
      statistic of 1.4, and mean group difference of 23.5 (95% confidence interval 17.4
      29.6) were obtained. INTERPRETATION: The Drooling Impact Scale is a valid and
      reliable subjective measure that is responsive to change.

PMID- 19843156
TI  - Activated complement is more extensively present in diseased aortic valves than
      naturally occurring complement inhibitors: a sign of ongoing inflammation.
AB  - BACKGROUND: Recent studies indicate a role for complement in the pathogenesis of
      aortic valve disease. However, the role of naturally occurring anti-complement
      mediators in this context is unknown. In this study, we have analysed this in
      three different pathological conditions of the aortic valve: degeneration,
      atherosclerosis and bacterial endocarditis. MATERIALS AND METHODS: Human aortic
      valves were obtained at autopsy (n = 30): 5 control valves, 10 aortic valves with
      atherosclerotic changes, 10 aortic valves with degenerative changes and 5
      degenerative changed aortic valves with bacterial infection. These valves were
      analysed immunohistochemically for the presence of activated complement (C3d and
      C5b9) and the complement inhibitors C1-inh and clusterin. Areas of positivity
      were then quantified. RESULTS: C3d, C5b9 and the complement inhibitors C1-inh and
      clusterin depositions were mainly found in the endothelium and extracellular
      matrix in aortic valves. All these mediators were already present in control
      valves, but the area of positivity increased significantly in response to the
      different diseases, with the highest increase in response to bacterial
      endocarditis. Interestingly, in all three aortic diseases, the depositions of
      complement were significantly more widespread than that of their inhibitors.
      CONCLUSIONS: Our study indicates that anti-complement mediators (C1-inh and
      clusterin) are deposited in diseased aortic valves together with activated
      complement, indicating an existing counter response against complement locally in
      the valve. However, deposition of activated complement is significantly more
      widespread than that of its inhibitors, which could explain ongoing inflammation
      in those diseased aortic valves.

PMID- 19843157
TI  - Outcome after device implantation in chronic heart failure is dependent on
      concomitant medical treatment.
AB  - BACKGROUND: Device implantation in chronic heart failure (CHF) for cardiac
      resynchronization therapy (CRT) with or without implantable
      cardioverter/defibrillator (ICD) is an established treatment option for
      symptomatic patients under medical baseline therapy. Although recommended, the
      need for optimization of medical therapy was never proven. As in 'the real
      world', medical therapy is not always up-titrated to the desirable dosages; this
      provides the opportunity to evaluate the impact of optimizing medical therapy in
      patients who had received a device therapy with proven effectiveness. MATERIALS
      AND METHODS: This observational cohort study retrospectively assessed the 'real
      life'-effect of CRT compared with that of CRT/ICD therapy and the impact of
      concomitant pharmacotherapy on outcome. Outcome of patients with guideline
      recommended renin-angiotensin system inhibitor and ss-blocker dosages was
      compared with that of patients who failed to reach the desired dosages. Mean
      follow-up for the 205 CHF (95 CRT and 110 CRT/ICD) patients was 16.8 + or - 12.4
      months. RESULTS: In the total study cohort, 83 (41%) reached the combined primary
      endpoint of all-cause death or cardiac hospitalization [CRT group: 25 (26%),
      CRT/ICD group: 58 (52.7%), P < 0.001]. Multiple cox regression analysis revealed
      non-optimized medical therapy at follow-up [HR = 2.080 (1.166-3.710), P = 0.013]
      and CRT/ICD vs. CRT [HR = 2.504 (1.550-4.045), P < 0.001] as significant
      predictors of the primary endpoint. CONCLUSION: Our data stress the importance of
      professional monitoring and titration of pharmacotherapy not only in medically
      treated CHF patients but also in patients under device therapy by a heart failure
      unit or a specialized cardiologist.

PMID- 19843159
TI  - Assembly of nuclear DNA-encoded subunits into mitochondrial complex IV, and their
      preferential integration into supercomplex forms in patient mitochondria.
AB  - Complex IV is the terminal enzyme of the mitochondrial respiratory chain. In
      humans, biogenesis of complex IV involves the coordinated assembly of 13 subunits
      encoded by both mitochondrial and nuclear genomes. The early stages of complex IV
      assembly involving mitochondrial DNA-encoded subunits CO1 and CO2 have been well
      studied. However, the latter stages, during which many of the nuclear DNA-encoded
      subunits are incorporated, are less well understood. Using in vitro import and
      assembly assays, we found that subunits Cox6a, Cox6b and Cox7a assembled into pre
      existing complex IV, while Cox4-1 and Cox6c subunits assembled into subcomplexes
      that may represent rate-limiting intermediates. We also found that Cox6a and
      Cox7a are incorporated into a novel intermediate complex of approximately 250
      kDa, and that transition of subunits from this complex to the mature holoenzyme
      had stalled in the mitochondria of patients with isolated complex IV deficiency.
      A number of complex IV subunits were also found to integrate into supercomplexes
      containing combinations of complex I, dimeric complex III and complex IV. Subunit
      assembly into these supercomplexes was also observed in mitochondria of patients
      in whom monomeric complex IV was selectively reduced. We conclude that newly
      imported nuclear DNA-encoded subunits can integrate into the complex IV
      holoenzyme and supercomplex forms by associating with pre-existing subunits and
      intermediate assembly complexes.

PMID- 19843160
TI  - MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in
      HCT116 human colorectal cancer cells.
AB  - MicroRNAs are aberrantly expressed in cancer; microRNA-143 (miR-143) is down
      regulated in colon cancer. HCT116 human colorectal cancer cells were used to
      investigate the biological role of miR-143. Transient miR-143 overexpression
      resulted in an approximate 60% reduction in cell viability. In addition, stable
      miR-143 overexpressing cells were selected with G418 and exposed to 5
      fluorouracil. Increased stable expression of miR-143 was associated with
      decreased viability and increased cell death after exposure to 5-fluorouracil.
      These changes were associated with increased nuclear fragmentation and caspase 
      3, -8 and -9 activities. In addition, extracellular-regulated protein kinase 5,
      nuclear factor-kappaB and Bcl-2 protein expression was down-regulated by miR-143,
      and further reduced by exposure to 5-fluorouracil. In conclusion, miR-143
      modulates the expression of key proteins involved in the regulation of cell
      proliferation, death and chemotherapy response. In addition, miR-143 increases
      the sensitivity of colon cancer cells to 5-fluorouracil, probably acting through
      extracellular-regulated protein kinase 5/nuclear factor-kappaB regulated
      pathways. Collectively, the data obtained in the present study suggest anti
      proliferative, chemosensitizer and putative pro-apoptotic roles for miR-143 in
      colon cancer.

PMID- 19843161
TI  - Space, time and nitric oxide--neuronal nitric oxide synthase generates signal
      pulses.
AB  - The temporal aspects of signaling are critical to the function of signals in
      communications, feedback regulation and control. The production and transduction
      of biological signals by enzymes comprises an area of central importance and
      rapid progress in the biomedical sciences. Treatment of signaling enzymes almost
      universally employs steady-state analyses that are suitable for mass catalysis
      but inappropriate for components in an information channel or a feedback/control
      system. In the present study, we show that, at 37 degrees C, neuronal nitric
      oxide synthase (EC 1.14.13.39) is progressively inhibited by the formation of an
      inhibited state during the first few turnovers (approximately 200 ms) after the
      initiation of catalysis, leading to pulse formation of nitric oxide. The general
      mechanism may be of wide importance in biological signaling.

PMID- 19843162
TI  - The N-terminus of mature human frataxin is intrinsically unfolded.
AB  - Frataxin is a highly conserved nuclear-encoded mitochondrial protein whose
      deficiency is the primary cause of Friedreich's ataxia, an autosomal recessive
      neurodegenerative disease. The frataxin structure comprises a well-characterized
      globular domain that is present in all species and is preceded in eukaryotes by a
      non-conserved N-terminal tail that contains the mitochondrial import signal.
      Little is known about the structure and dynamic properties of the N-terminal
      tail. Here, we show that this region is flexible and intrinsically unfolded in
      human frataxin. It does not alter the iron-binding or self-aggregation properties
      of the globular domain. It is therefore very unlikely that this region could be
      important for the conserved functions of the protein.

PMID- 19843163
TI  - The nucleosome-binding protein HMGN2 modulates global genome repair.
AB  - The HMGN family comprises nuclear proteins that bind to nucleosomes and alter the
      structure of chromatin. Here, we report that DT40 chicken cells lacking either
      HMGN2 or HMGN1a, or lacking both HMGN1a and HMGN2, are hypersensitive to killing
      by UV irradiation. Loss of both HMGN1a and HMGN2 or only HMGN2 increases the
      extent of UV-induced G(2)-M checkpoint arrest and the rate of apoptosis. HMGN
      null mutant cells showed slower removal of UV-induced DNA lesions from native
      chromatin, but the nucleotide excision repair remained intact, as measured by
      host cell reactivation assays. These results identify HMGN2 as a component of the
      global genome repair subpathway of the nucleotide excision repair pathway, and
      may indicate that HMGN2 facilitates the ability of the DNA repair proteins to
      access and repair UV-induced DNA lesions in chromatin. Our finding that HMGNs
      play a role in global DNA repair expands the role of these proteins in the
      maintenance of genome integrity.

PMID- 19843165
TI  - Arabidopsis thaliana BTB/ POZ-MATH proteins interact with members of the ERF/AP2
      transcription factor family.
AB  - In Arabidopsis thaliana, the BTB/POZ-MATH (BPM) proteins comprise a small family
      of six members. They have been described previously to use their broad complex,
      tram track, bric-a-brac/POX virus and zinc finger (BTB/POZ) domain to assemble
      with CUL3a and CUL3b and potentially to serve as substrate adaptors to cullin
      based E3-ligases in plants. In this article, we show that BPMs can also assemble
      with members of the ethylene response factor/Apetala2 transcription factor
      family, and that this is mediated by their meprin and TRAF (tumor necrosis factor
      receptor-associated factor) homology (MATH) domain. In addition, we provide a
      detailed description of BPM gene expression patterns in different tissues and on
      abiotic stress treatments, as well as their subcellular localization. This work
      connects, for the first time, BPM proteins with ethylene response factor/Apetala2
      family members, which is likely to represent a novel regulatory mechanism of
      transcriptional control.

PMID- 19843164
TI  - Crystal structure of the shutoff and exonuclease protein from the oncogenic
      Kaposi's sarcoma-associated herpesvirus.
AB  - The Kaposi's sarcoma-associated herpesvirus protein SOX (shut off and
      exonuclease) and its Epstein-Barr virus homolog, BGLF5, are active during the
      early lytic phase and belong to the alkaline nuclease family. Both proteins have
      been shown to be bifunctional, being responsible for DNA maturation as well as
      host shutoff at the mRNA level. We present the crystal structure of SOX
      determined at 1.85 A resolution. By modeling DNA binding, we have identified
      catalytic residues that explain the preferred 5'-exonuclease activity of the
      alkaline nucleases. The presence of a crevice suitable for binding duplex DNA
      supports a role for herpes alkaline nucleases in recombination events preceding
      packaging of viral DNA. Direct interaction with dsDNA is supported by
      oligonucleotide binding data. Mutations specifically affecting host shutoff map
      to a surface region of the N-terminal domain, implying an essential role in
      protein-protein interactions, and link the RNase activity of the enzyme to mRNA
      degradation pathways.

PMID- 19843166
TI  - The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon
      semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests
      a regulatory link between NAD synthesis and glycolysis.
AB  - The enzyme alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
      (ACMSD) is a zinc-dependent amidohydrolase that participates in picolinic acid
      (PA), quinolinic acid (QA) and NAD homeostasis. Indeed, the enzyme stands at a
      branch point of the tryptophan to NAD pathway, and determines the final fate of
      the amino acid, i.e. transformation into PA, complete oxidation through the
      citric acid cycle, or conversion into NAD through QA synthesis. Both PA and QA
      are key players in a number of physiological and pathological conditions, mainly
      affecting the central nervous system. As their relative concentrations must be
      tightly controlled, modulation of ACMSD activity appears to be a promising
      prospect for the treatment of neurological disorders, including cerebral malaria.
      Here we report the 2.0 A resolution crystal structure of human ACMSD in complex
      with the glycolytic intermediate 1,3-dihydroxyacetonephosphate (DHAP), refined to
      an R-factor of 0.19. DHAP, which we discovered to be a potent enzyme inhibitor,
      resides in the ligand binding pocket with its phosphate moiety contacting the
      catalytically essential zinc ion through mediation of a solvent molecule. Arg47,
      Asp291 and Trp191 appear to be the key residues for DHAP recognition in human
      ACMSD. Ligand binding induces a significant conformational change affecting a
      strictly conserved Trp-Met couple, and we propose that these residues are
      involved in controlling ligand admission into ACMSD. Our data may be used for the
      design of inhibitors with potential medical interest, and suggest a regulatory
      link between de novo NAD biosynthesis and glycolysis.

PMID- 19843167
TI  - Cholesterol oxidase: biotechnological applications.
AB  - Cholesterol oxidase is a bacterial FAD-containing flavooxidase that catalyzes the
      first reaction in cholesterol catabolism. Indeed, this enzyme catalyzes two
      reactions: the oxidation of the C(3)-OH group of cholesterol (and other sterols)
      to give cholest-5-en-3-one; and its isomerization to cholest-4-en-3-one. In the
      past several years, the structural and functional characterization of cholesterol
      oxidase has been developed together with its application as a biological tool.
      Cholesterol oxidase has been used in biocatalysis for the production of a number
      of steroids, as an insecticidal protein against boll weevil larvae and, in
      particular, as a diagnostic enzyme for determining serum levels of cholesterol.
      These applications prompted various laboratories worldwide to isolate this
      flavooxidase from different sources and to improve its properties by protein
      engineering, further increasing our knowledge on its structure-function
      relationships. These studies also discovered new physiological roles for
      cholesterol oxidase (e.g. in virulence and as an antifungal sensor). We assume
      that the investigations of cholesterol oxidase and its applications will continue
      to grow quickly in the near future, in particular to uncover unexpected, new
      areas of application.

PMID- 19843169
TI  - Cholesterol oxidase: biochemistry and structural features.
AB  - Cholesterol oxidases are bifunctional flavoenzymes that catalyze the oxidation of
      steroid substrates which have a hydroxyl group at the 3beta position of the
      steroid ring system. The enzyme is found, in a wide range of bacterial species,
      in two forms: one with the FAD cofactor bound noncovalently to the enzyme; and
      one with the cofactor linked covalently to the protein. Here we discuss, compare
      and contrast the salient biochemical properties of the two forms of the enzyme.
      Specifically, the structural features are discussed that affect the redox
      potentials of the flavin cofactor, the chemical mechanism of substrate
      dehydrogenation by active-center amino acid residues, the kinetic parameters of
      both types of enzymes and the reactivity of reduced enzymes with molecular
      dioxygen. The presence of a molecular tunnel that is proposed to serve in the
      access of dioxygen to the active site and mechanisms of its control by a 'gate'
      formed by amino acid residues are highlighted.

PMID- 19843168
TI  - Cholesterol oxidase: physiological functions.
AB  - An important aspect of catalysis performed by cholesterol oxidase (3beta
      hydroxysteroid oxidase) concerns the nature of its association with the lipid
      bilayer that contains the sterol substrate. Efficient catalytic turnover is
      affected by the association of the protein with the membrane as well as the
      solubility of the substrate in the lipid bilayer. In this review, the binding of
      cholesterol oxidase to the lipid bilayer, its turnover of substrates presented in
      different physical environments, and how these conditions affect substrate
      specificity, are discussed. The physiological functions of the enzyme in
      bacterial metabolism, pathogenesis and macrolide biosynthesis are reviewed in
      this context.

PMID- 19843170
TI  - Cholesterol oxidase: a model flavoprotein oxidase and a biotechnological tool.

PMID- 19843171
TI  - ERK and cell death: cadmium toxicity, sustained ERK activation and cell death.
AB  - Extracellular signal-related kinase (ERK) is a key player in cell signaling.
      After 25 years of investigation, ERK has been associated with every major aspect
      of cell physiology. Cell proliferation, cell transformation, protection against
      apoptosis, among others, are influenced by ERK function. Surprisingly, ERK has
      also been associated with two apparently opposing processes. The involvement of
      ERK in cell proliferation has been extensively described, as well as its function
      in postmitotic cells undergoing differentiation. The analysis of these apparent
      discrepancies has led to a more precise understanding of the multiple functions
      and regulations of ERK. More recently, several groups have identified a new and
      unexpected role for ERK. Although being accepted as an important player in the
      protection against cell death by apoptosis, it is now clear that ERK can also be
      directly linked to cell death signaling. Here, we review the role of ERK in cell
      response to cadmium and its association with cell toxicity. In this system, ERK
      is subjected to a continuous activation that can last for days, which ultimately
      results in cell death. Cadmium entry into cells is responsible for this sustained
      ERK activation, probably via reactive oxygen species production, and protein
      kinase C has a negative action on this cadmium-dependent ERK activation by
      modulating cadmium entry into cells.

PMID- 19843172
TI  - ERK and cell death: ERK location and T cell selection.
AB  - The selection of functional T cells is mediated by interactions between the T
      cell antigen receptor and self-peptide major histocompatibility complex expressed
      on thymic epithelium. These interactions either lead to survival and development
      or death. The T cell antigen receptor is an unusual receptor able to signal
      multiple cell fates. The precise mechanism by which this is achieved has been an
      area of intense research effort over the years. One model proposes that the
      differential activation of mitogen-activated protein kinase pathways contributes
      to this decision. Here, the role of extracellular signal-regulated kinase in
      promoting or preventing apoptosis during thymic selection is discussed.

PMID- 19843173
TI  - ERK and cell death: ERK1/2 in neuronal death.
AB  - Extracellular signal-regulated kinase (ERK) is a versatile protein kinase that
      regulates many cellular functions. Growing evidence suggests that ERK1/2 plays a
      crucial role in promoting cell death in a variety of neuronal systems, including
      neurodegenerative diseases. It is believed that the magnitude and the duration of
      ERK1/2 activity determine its cellular function. In this review, we summarize
      recent evidence for a role of ERK1/2 in neuronal death. Furthermore, we discuss
      the mechanisms involved in ERK1/2 mediating neuronal death.

PMID- 19843174
TI  - ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy
      and senescence.
AB  - The Ras/Raf/extracellular signal-regulated kinase (ERK) signaling pathway plays a
      crucial role in almost all cell functions and therefore requires exquisite
      control of its spatiotemporal activity. Depending on the cell type and stimulus,
      ERK activity will mediate different antiproliferative events, such as apoptosis,
      autophagy and senescence in vitro and in vivo. ERK activity can promote either
      intrinsic or extrinsic apoptotic pathways by induction of mitochondrial
      cytochrome c release or caspase-8 activation, permanent cell cycle arrest or
      autophagic vacuolization. These unusual effects require sustained ERK activity in
      specific subcellular compartments and could depend on the presence of reactive
      oxygen species. We will summarize the mechanisms involved in Ras/Raf/ERK
      antiproliferative functions.

PMID- 19843175
TI  - ERK and cell death: overview.

PMID- 19843177
TI  - Towards a platform for the metabonomic profiling of different strains of
      Drosophila melanogaster using liquid chromatography-Fourier transform mass
      spectrometry.
AB  - A platform based on hydrophilic interaction chromatography in combination with
      Fourier transform mass spectrometry was developed in order to carry out
      metabonomics of Drosophila melanogaster strains. The method was able to detect
      approximately 230 metabolites, mainly in the positive ion mode, after checking to
      eliminate false positives caused by isotope peaks, adducts and fragment ions. Two
      wild-type strains, Canton S and Oregon R, were studied, plus two mutant strains,
      Maroon Like and Chocolate. In order to observe the differential expression of
      metabolites, liquid chromatography-mass spectrometry analyses of the different
      strains were compared using sieve 1.2 software to extract metabolic differences.
      The output from sieve was searched against a metabolite database using an Excel
      based macro written in-house. Metabolic differences were observed between the
      wild-type strains, and also between both Chocolate and Maroon Like compared with
      Oregon R. It was established that a metabonomic approach could produce results
      leading to the generation of new hypotheses. In addition, the structure of a new
      class of lipid with a histidine head group, found in all of the strains of flies,
      but lower in Maroon Like, was elucidated.

PMID- 19843176
TI  - Zinc finger transcription factor ecotropic viral integration site 1 is induced by
      all-trans retinoic acid (ATRA) and acts as a dual modulator of the ATRA response.
AB  - Ecotropic viral integration site 1 (EVI1) plays important roles in leukaemia and
      development, and its expression is temporally and spatially highly restricted
      during the latter process. Nevertheless, the only physiological agent that to
      date has been shown to regulate transcription of this gene in mammalian cells is
      all-trans retinoic acid. Here we describe the identification of a retinoic acid
      response element that was located in the most distal of several alternative first
      exons of the human EVI1 gene and was constitutively bound by canonical retinoid
      receptors in NTERA-2 teratocarcinoma cells. Furthermore, it was the target of
      negative feedback by EVI1 on the induction of its own promoter by retinoic acid.
      This process required a previously described transcription repression domain of
      EVI1. Extending its role as a modulator of the retinoic acid response, EVI1 had
      the opposite effect on the RARbeta retinoic acid response element, whose
      induction by all-trans retinoic acid it enhanced through a mechanism that
      involved almost all of its known functional domains. Augmentation of the retinoic
      acid response by EVI1 was also observed for the endogenous RARbeta gene. Thus, we
      have established EVI1 as a novel type of modulator of the retinoic acid response,
      which can both enhance and repress induction by this agent in a promoter-specific
      manner.

PMID- 19843178
TI  - Differential tissue-specific distribution of transcripts for the duplicated fatty
      acid-binding protein 10 (fabp10) genes in embryos, larvae and adult zebrafish
      (Danio rerio).
AB  - Genomic and cDNA sequences coding for a fatty acid-binding protein (FABP) in
      zebrafish were retrieved from DNA sequence databases. The cDNA codes for a
      protein of 14.7 kDa (pI = 5.94), and the gene consists of four exons, properties
      characteristic of most vertebrate FABP genes. Phylogenetic analyses using
      vertebrate FABPs indicated that this protein is most similar to zebrafish Fabp10.
      Currently, only one fabp10 gene is annotated in the zebrafish genome. In this
      article, the notations 'fabp10a' and 'fabp10b' are used to refer to the duplicate
      copies of fabp10. The zebrafish fabp10a and fabp10b genes were assigned by
      radiation hybrid mapping to chromosomes 16 and 19, respectively. On the basis of
      conserved gene synteny with chicken FABP10 on chromosome 23, zebrafish fabp10a
      and fabp10b are duplicates resulting from a whole-genome duplication event early
      in the ray-finned fish lineage some 230-400 million years ago. Whole-mount in
      situ hybridization detected fabp10b transcripts only in the olfactory vesicles of
      embryos and larvae, whereas fabp10a transcripts have been shown previously to be
      present only in the liver of embryos and larvae. In adults, RT-PCR detected
      fabp10b transcripts in all tissues assayed. By contrast, fabp10a transcripts were
      detected only in adult liver, intestine and testis. This differential tissue
      distribution of transcripts for the duplicated fabp10 genes suggests considerable
      divergence of their cis-acting regulatory elements since their duplication.

PMID- 19843179
TI  - Dermaseptin DA4, although closely related to dermaseptin B2, presents chemotactic
      and Gram-negative selective bactericidal activities.
AB  - Antimicrobial peptides participate in innate host defense by directly eliminating
      pathogens as a result of their ability to damage the microbial membrane and by
      providing danger signals that will recruit innate immune cells to the site of
      infection. Dermaseptin DA4 (DRS-DA4), a new antimicrobial peptide of the
      dermaseptin superfamily, was identified based on its chemotactic properties,
      contrasting with the currently used microbicidal properties assessment. The
      peptide was isolated and purified by size exclusion HPLC and RP-HPLC from the
      skin of the Mexican frog, Pachymedusa dacnicolor. MS and amino acid sequence
      analyses were consistent with the structure GMWSKIKNAGKAAKAAAKAAGKAALGAVSEAM. CD
      experiments showed that, unlike most antimicrobial peptides of the dermaseptin
      superfamily, DRS-DA4 is not structured in the presence of zwitterionic lipids.
      DRS-DA4 is a potent chemoattractant for human leukocytes and is devoid of
      hemolytic activity; in addition, bactericidal tests and membrane perturbation
      assays on model membranes and on Escherichia coli and Staphylococcus aureus
      strains have shown that the antibacterial effects of DRS-DA4 and permeabilization
      of the inner membrane are exclusively selective for Gram-negative bacteria.
      Interestingly, despite high sequence homology with dermaseptin S4, dermaseptin B2
      was not able to induce directional migration of leukocytes, and displayed a
      broader bactericidal spectrum. A detailed structure-function analysis of closely
      related peptides with different capabilities, such as DRS-DA4 and dermaseptin B2,
      is critical for the design of new molecules with specific attributes to modulate
      immunity and/or act as microbicidal agents.

PMID- 19843181
TI  - Functional and small-angle X-ray scattering studies of a new stationary phase
      survival protein E (SurE) from Xylella fastidiosa--evidence of allosteric
      behaviour.
AB  - The genome data of bacterium Xylella fastidiosa strain 9a5c has identified
      several orfs related to its phytopathogenic adaptation and survival. Among these
      genes, the surE codifies a survival protein E (XfSurE) whose function is not so
      well understood, but functional assays in Escherichia coli revealed nucleotidase
      and exopolyphosphate activity. In the present study, we report the XfSurE protein
      overexpression in E. coli and its purification. The overall secondary structure
      was analyzed by CD. Small-angle X-ray scattering and gel filtration techniques
      demonstrated that the oligomeric state of the protein in solution is a tetramer.
      In addition, functional kinetics experiments were carried out with several
      monophosphate nucleoside substrates and revealed a highly positive cooperativity.
      An allosteric mechanism involving torsion movements in solution is proposed to
      explain the cooperative behaviour of XfSurE. This is the first characterization
      of a SurE enzyme from a phytopathogen organism and, to our knowledge, the first
      solution structure of a SurE protein to be described.

PMID- 19843180
TI  - Effect of citrullination on the function and conformation of antithrombin.
AB  - Antithrombin is an anticoagulant serpin with conformational sensitivity.
      Mutations and environmental factors may induce its polymerization by a mechanism
      involving domain swapping, which still requires verification. We have evaluated
      the functional and conformational effects on antithrombin of citrullination, a
      post-translational modification catalyzed by peptidylarginine deiminase (PAD),
      which changes arginine to citrulline. Purified antithrombin (native and latent
      forms) and plasma were incubated with PAD in the presence and absence of heparin.
      Citrullines were identified by proteomic analysis. Anti-activated factor X
      activity determination, IEF, SDS/PAGE and native PAGE were performed. The
      cleavage pattern with the metalloprotease AspN was studied, and its target
      residues were identified by Edman sequencing. We confirmed that citrullination of
      antithrombin abolished its activity; this abolition of activity was accelerated
      by heparin, which facilitated the early citrullination of Arg393 (P1 residue).
      Proteomic analyses revealed nine additional citrullines that caused a significant
      decrease in its electrostatic potential (from 5.95 to 5.06). It was demonstrated
      that citrullination of antithrombin caused its polymerization. The observation
      that these polymers, like heat-generated polymers, are cleaved by AspN in helix I
      is compatible with their linkage by domain swapping from strand 5 to strand 4 of
      beta-sheet A.

PMID- 19843182
TI  - Site-directed enzymatic PEGylation of the human granulocyte colony-stimulating
      factor.
AB  - Poly(ethylene glycol) (PEG) is a widely used polymer employed to increase the
      circulating half-life of proteins in blood and to decrease their immunogenicity
      and antigenicity. PEG attaches to free amines, typically at lysine residues or at
      the N-terminal amino acid. This lack of selectivity can present problems when a
      PEGylated protein therapeutic is being developed, because predictability of
      activity and manufacturing reproducibility are needed for regulatory approval.
      Enzymatic modification of proteins is one route to overcome this limitation.
      Bacterial transglutaminases are enzyme candidates for site-specific modification,
      but they also have rather broad specificity. The need arises to be able to
      predict a priori potential PEGylation sites on the protein of interest and,
      especially, to be able to design mutants where unique PEGylation sites can be
      introduced when needed. We investigated the feasibility of a computational
      approach to the problem, using human granulocyte colony-stimulating factor as a
      test case. The selected protein is therapeutically relevant and represents a
      challenging problem, as it contains 17 potential PEGylation sites. Our results
      show that a combination of computational methods allows the identification of the
      specific glutamines that are substrates for enzymatic PEGylation by a microbial
      transglutaminase, and that it is possible to rationally modify the protein and
      introduce PEG moieties at desired sites, thus allowing the selection of regions
      that are unlikely to interfere with the biological activity of a therapeutic
      protein.

PMID- 19843183
TI  - UDP-galactose 4-epimerase from Kluyveromyces fragilis--catalytic sites of the
      homodimeric enzyme are functional and regulated.
AB  - UDP-galactose 4-epimerase from Kluyveromyces fragilis is a homodimer containing
      one catalytic site and one NAD(+) as cofactor per subunit. One 5'-UMP, a
      competitive inhibitor, binds per dimer of epimerase as isolated and causes
      inactivation. Addition of 0.2 mm inhibitor to the enzyme in vitro leads to three
      sequential steps: first, the inhibitor binds to the unoccupied site; second, the
      inhibitor bound ex vivo is displaced allosterically; and finally, both sites are
      occupied by the inhibitor. These reactions have been monitored by kinetic lag in
      substrate conversion, coenzyme fluorescence, protection against trypsin
      digestion, and reductive inhibition. The transition profiles indicate the
      existence of a stable intermediate with one inhibitor-binding site remaining
      unoccupied. Reductive inhibition of this intermediate reduced the activity to 58%
      +/- 2%, with modification of one catalytic site. A change of conformation of the
      epimerase upon binding with substrate or inhibitor was evident from fluorescence
      emission spectra. The epimerase demonstrated a biphasic Michaelis-Menten
      dependency. The epimerase devoid of 5'-UMP showed a Michaelis-Menten dependency
      that can be explained by assuming simultaneous operation of two catalytic sites.
      A monomeric form of the epimerase was devoid of such regulation. The inhibitory
      profile of 5'-UMP also suggested negative cooperativity. Incubation of the
      epimerase with combinations of substrate analogs rendered one of the sites
      inactive, supporting the presence of two functional and regulated catalytic
      sites. Dissimilar kinetic patterns of the reconstituted enzyme after treatment
      with p-chloromercuribenzoate indicated stability of the dimeric enzyme against
      fast association-dissociation, which could otherwise generate multiple forms of
      the enzyme with functional heterogeneity.

PMID- 19843184
TI  - NF-kappaB regulates the transcription of protein tyrosine kinase Tec.
AB  - The tyrosine kinase expressed in hepatocellular carcinoma (Tec) is a non-receptor
      protein tyrosine kinase (PTK) that is expressed in hematopoietic cells, such as B
      and T lymphocytes, myeloid lineage cells and neutrophils. Mutations in the human
      Btk gene cause X-linked agammaglobulinemia (XLA), but the corresponding mutation
      in mice results in a much milder defect. However, the combined inactivation of
      Btk and Tec genes in mice cause a severe phenotype resembling XLA. Tec is
      involved in the regulation of both B and T lymphocytes, fine-tuning of TCR/BCR
      signaling, and also activation of the nuclear factor of activated T cells.
      Previous work has shown that the transcription factors Sp1 and PU.1 can bind and
      regulate the Tec promoter. In this study, we demonstrate that NF-kappaB is an
      essential transcription factor for optimal expression of the Tec gene, and
      identify a unique functionally active NF-kappaB binding site in its promoter. The
      NF-kappaB subunit p65/RelA directly induced transcriptional activity of the Tec
      promoter. Moreover, we also found that proteasome inhibitors, including
      Bortezomib, repress Tec transcription through inactivation of the NF-kappaB
      signaling pathway. This study, together with our previous findings on the
      transcriptional regulation of Btk (Bruton's tyrosine kinase) by proteasome
      inhibitors, provides important insight into the molecular mechanism(s) underlying
      the role of NF-kappaB in Tec family kinase signaling and lymphocyte development.

PMID- 19843185
TI  - Polypyrimidine tract-binding protein is essential for early mouse development and
      embryonic stem cell proliferation.
AB  - Polypyrimidine tract-binding protein (PTB) is a widely expressed RNA-binding
      protein with multiple roles in RNA processing, including the splicing of
      alternative exons, mRNA stability, mRNA localization, and internal ribosome entry
      site-dependent translation. Although it has been reported that increased
      expression of PTB is correlated with cancer cell growth, the role of PTB in
      mammalian development is still unclear. Here, we report that a homozygous
      mutation in the mouse Ptb gene causes embryonic lethality shortly after
      implantation. We also established Ptb(-/-) embryonic stem (ES) cell lines and
      found that these mutant cells exhibited severe defects in cell proliferation
      without aberrant differentiation in vitro or in vivo. Furthermore, cell cycle
      analysis and a cell synchronization assay revealed that Ptb(-/-) ES cells have a
      prolonged G(2)/M phase. Thus, our data indicate that PTB is essential for early
      mouse development and ES cell proliferation.

PMID- 19843186
TI  - QuantiFERON-TB GOLD ELISA assay for the detection of Mycobacterium tuberculosis
      specific antigens in blood specimens of HIV-positive patients in a high-burden
      country.
AB  - Tuberculosis is a life-threatening infection worldwide. Despite improvements in
      therapy, it results in 2 million deaths and 9 million new cases annually. This
      study evaluated the use of the QuantiFERON-TB GOLD enzyme-linked immunosorbent
      assay in a high HIV/TB burden setting in an ARV clinic at the Tshwane District
      Hospital, South Africa. The sensitivity and specificity of the QF assay in the
      clinic were 30% (9/30) and 63% (19/30), respectively, when compared with the gold
      standard culture results. Analysis also suggested that the sensitivity of the
      QuantiFERON assay is determined by a limiting patient CD4 value between 150 and
      200.

PMID- 19843187
TI  - Not so old Archaea - the antiquity of biogeochemical processes in the archaeal
      domain of life.
AB  - Since the archaeal domain of life was first recognized, it has often been assumed
      that Archaea are ancient, and harbor primitive traits. In fact, the names of the
      major archaeal lineages reflect our assumptions regarding the antiquity of their
      traits. Ancestral state reconstruction and relaxed molecular clock analyses using
      newly articulated oxygen age constraints show that although the archaeal domain
      itself is old, tracing back to the Archean eon, many clades and traits within the
      domain are not ancient or primitive. Indeed many clades and traits, particularly
      in the Euryarchaeota, were inferred to be Neoproterozoic or Phanerozoic in age.
      Both Eury- and Crenarchaeota show increasing metabolic and physiological
      diversity through time. Early archaeal microbial communities were likely limited
      to sulfur reduction and hydrogenotrophic methanogenesis, and were confined to
      high-temperature geothermal environments. However, after the appearance of
      atmospheric oxygen, nodes containing a wide variety of traits (sulfate and
      thiosulfate reduction, sulfur oxidation, sulfide oxidation, aerobic respiration,
      nitrate reduction, mesophilic methanogenesis in sedimentary environments) appear,
      first in environments containing terrestrial Crenarchaeota in the
      Meso/Neoproterozoic followed by environments containing marine Euryarchaeota in
      the Neoproterozoic and Phanerozoic. This provides phylogenetic evidence for
      increasing complexity in the biogeochemical cycling of C, N, and S through
      geologic time, likely as a consequence of microbial evolution and the gradual
      oxygenation of various compartments within the biosphere. This work has
      implications not only for the large-scale evolution of microbial communities and
      biogeochemical processes, but also for the interpretation of microbial
      biosignatures in the ancient rock record.

PMID- 19843188
TI  - Sequencing of Spodoptera frugiperda midgut trehalases and demonstration of
      secretion of soluble trehalase by midgut columnar cells.
AB  - Both soluble (SfTre1) and membrane-bound (SfTre2) trehalases occur along the
      midgut of Spodoptera frugiperda larvae. Released SfTre2 was purified as a 67 kDa
      protein. Its K(m) (1.6 mM) and thermal stability (half life 10 min at 62 degrees
      C) are different from the previously isolated soluble trehalase (K(m)= 0.47 mM;
      100% stable at 62 degrees C). Two cDNAs coding for S. frugiperda trehalases have
      been cloned using primers based on consensus sequences of trehalases and having
      as templates a cDNA library prepared from total polyA-containing RNA extracted
      from midguts. One cDNA codes for a trehalase that has a predicted transmembrane
      sequence and was defined as SfTre2. The other, after being cloned and expressed,
      results in a recombinant trehalase with a K(m) value and thermal stability like
      those of native soluble trehalase. This enzyme was defined as SfTre1 and, after
      it was used to generate antibodies, it was immunolocalized at the secretory
      vesicles and at the glycocalyx of columnar cells. Escherichia coli trehalase 3D
      structure and sequence alignment with SfTre1 support a proposal regarding the
      residue modulating the pKa value of the proton donor.

PMID- 19843189
TI  - Utilization of (111)In-Capromab pendetide SPECT-CT for detecting seminal vesicle
      invasion with recurrent prostate cancer after primary in situ therapy.
AB  - The aim of this study was to evaluate the diagnostic value of a hybrid (111)In
      capromab pendetide fused computed tomography (CT) scan in detecting seminal
      vesicle invasion (SVI) in the setting of recurrent prostate cancer following
      primary in situ therapy. The study population comprised 59 patients, who
      biochemically failed primary in situ treatment based on American Society for
      Therapeutic Radiology and Oncology criteria. The patients underwent an (111)In
      capromab pendetide/CT scan at the time of biochemical failure with a prostate (12
      core) and seminal vesicle (SV) (8-core) biopsy. The diagnostic properties of the
      scan and magnetic resonance imaging (MRI) in detecting SVI compared to an SV
      biopsy were calculated. In total, eight (14%) patients had a positive SV biopsy
      after primary in situ prostate cancer treatment. Nine (15%) patients had positive
      uptake of the scan in the SV. When comparing the SV scan results to the SV
      biopsy, the sensitivity, specificity, positive predictive value, and negative
      predictive value were 37.5%, 88.2%, 33.3%, and 90.0% (95% confidence interval:
      0.44-0.81), respectively. In contrast, the ability of MRI to detect SVI was
      50.0%, 81.3%, 40.0%, and 86.7% (95% confidence interval: 0.46-0.85),
      respectively. Although the sensitivity and positive predictive value of the
      (111)In-capromab pendetide/CT scan are low, its specificity and negative
      predictive value are high. Based on these findings, the ability of the (111)In
      capromab pendetide/CT scan to detect SVI seems to be comparable with MRI.

PMID- 19843190
TI  - Emotion regulation, risk, and psychopathology.

PMID- 19843192
TI  - Clinical reliability of non-organoleptic oral malodour measurements.
AB  - AIM: Measurement of volatile sulphur compounds (VSC) by portable sulphur monitors
      (Halimeter, OralChroma) is a common practice for diagnosis of oral malodour. In
      this study, the clinical value of these devices was examined. MATERIALS AND
      METHODS: Two hundred and eighty patients with bad breath complaints attending a
      halitosis consultation were enrolled. Organoleptic scores were given by a trained
      and calibrated judge, before measurement of the VSC levels (Halimeter,
      OralChroma), to avoid any bias. RESULTS: Significant correlations were found
      between the organoleptic assessment, the Halimeter, and the OralChroma (R=0.74
      for organoleptic versus Halimeter; 0.66 for organoleptic versus OralChroma; 0.63
      for Halimeterversus OralChroma). The sensitivity and specificity (with regard to
      the organoleptic score) to detect patients with/without oral malodour for the
      Halimeter were 63% and 98%, respectively, and for the OralChroma 69% and 100%
      when using the cutoffs suggested by the manufacturer. By lowering these values,
      sensitivity could be improved without a significant decrease in specificity (both
      devices). CONCLUSIONS: We concluded that the measurement of the VSC levels can be
      used as an adjunct to the organoleptic assessment. Thresholds should be revisited
      in order to improve their clinical utility. These devices can prove the absence
      of malodour in case of pseudo-halitosis.

PMID- 19843193
TI  - Fibrofolliculoma with ancient/pseudosarcomatous features.
AB  - Fibrofolliculoma is a benign skin lesion that, when multiple, can be part of the
      Birt-Hogg-Dube syndrome. We report on a case of solitary fibrofolliculoma arisen
      on the nose of a 63-year-old woman, with peculiar histological and
      immunohistochemical features. The lesion was characterized by the presence of
      bizarre multinucleated perifollicular stromal cells, positive for factor XIIIa,
      in a background of CD34-positive cells, and by a peripheral population of CD34
      positive spindle cells organized in fascicles haphazardly infiltrating the deep
      dermis, and surrounded by scattered factor XIIIa-positive dendrocytes. We
      consider the bizarre perifollicular cellular component as an 'ancient' feature of
      fibrofolliculoma, hypothesis corroborated by the co-expression of CD34 and factor
      XIIIa, whereas the peripheral spindle cell fascicles represent a
      pseudosarcomatous proliferation of CD34-positive cells, normally surrounding
      adnexal structures, stimulated by factor XIIIa-positive dendrocytes.

PMID- 19843194
TI  - Melkersson Rosenthal syndrome: a histopathologic mystery and dermatologic
      challenge.
AB  - Melkersson Rosenthal syndrome (MRS) is rare disease of unknown etiology
      characterized by orofacial edema, facial nerve palsy and fissured tongue.
      Microscopically, it shows epithelioid non-caseous granulomas; however, edema and
      perivascular lymphocytic infiltrates have been described. Two different clinical
      forms of MRS are presented in this report. In the complete form (Case 1), the
      main histopathologic finding was a non-necrotizing granulomatous inflammation
      with 56% of the total number of cells composed of B cells (CD 20(+) ) principally
      located in the granuloma's center and 33% being T cells predominating in the
      surrounding area, of which 48% were CD 4(+) and 16% were CD 8(+) lymphocytes. In
      the monosymptomatic form (Case 2), the inflammatory cells were dispersed into the
      connective tissue without granulomatous formation. B cells were scanty, and 78%
      of the cells were CD 45(+) T cells, with 46% and 34%, CD 8(+) and CD 4(+)
      phenotype, respectively. These cases showed different clinical, histopathological
      and immunohistochemical forms of MRS, suggesting different host immune responses.

PMID- 19843195
TI  - Early-onset lichenoid graft-vs.-host disease: a unique variant of acute graft-vs.
      host disease occurring in peripheral blood stem cell transplant recipients.
AB  - BACKGROUND: A complication of stem cell transplantation is chronic graft-vs.-host
      disease (GvHD), developing months to years after transplant; the two commonest
      manifestations are lichenoid GvHD and scleroderma. The purpose of this study was
      to characterize early-onset lichenoid GvHD. METHODS: A retrospective study
      identified patients diagnosed with early-onset lichenoid GvHD. This diagnosis was
      correlated with type of transplant and concurrent or prior episodes of acute
      GvHD. RESULTS: Patients in whom a sex mismatch was present between donor and
      recipient were included, representing a study population of 17. All received an
      allogeneic peripheral blood stem cell transplant (PBSCT). All patients had biopsy
      proven lichenoid GvHD within 60 days or less following transplantation. All had
      concurrent gastrointestinal symptoms which was biopsy proven GvHD in thirteen of
      the cases. FISH XY studies revealed that the infiltrating lymphocytes were of
      donor origin in 12 of the cases, mixed in three and of host origin in two cases.
      CONCLUSIONS: Early-onset lichenoid GvHD is exclusive to the PBSCT setting and
      appears to be mediated by donor lymphocytes, reflecting the higher numbers of
      donor T cells encountered in PBSCT. We consider this reaction pattern a
      distinctive subtype of acute GvHD.

PMID- 19843196
TI  - Use of garlic, Allium sativum, to control Aeromonas hydrophila infection in
      rainbow trout, Oncorhynchus mykiss (Walbaum).
AB  - Garlic, Allium sativum, which was fed at 0, 0.05, 0.1, 0.5 and 1.0 g per 100 g of
      feed for 14 days to rainbow trout, Oncorhynchus mykiss (Walbaum), led to control
      of experimental infection with Aeromonas hydrophila. At doses of 0.5 and 1.0 g
      garlic per 100 g of feed, there was a reduction in mortalities to 4% compared
      with the controls (88%). Moreover, there was a significant increase in growth,
      feed conversion and protein efficiency. There was stimulation of the number of
      erythrocytes and leucocytes, a significantly higher haematocrit, enhancement of
      phagocytic activity, respiratory burst, lysozyme, anti-protease and bactericidal
      activities following feeding with garlic.

PMID- 19843197
TI  - Use of dietary ginger, Zingiber officinale Roscoe, as an immunostimulant to
      control Aeromonas hydrophila infections in rainbow trout, Oncorhynchus mykiss
      (Walbaum).
AB  - Ginger, Zingiber officinale, which was fed at 0, 0.05, 0.1, 0.5 and 1.0 g per 100
      g of feed for 14 days to rainbow trout, Oncorhynchus mykiss (Walbaum), led to
      control of experimental infection with Aeromonas hydrophila. At 0.5 g ginger per
      100 g of feed, there was a reduction in mortalities to 0% compared with the
      controls (64%). Moreover, there was a significant increase in growth, feed
      conversion and protein efficiency. There was proliferation in the number of
      neutrophils, macrophages and lymphocytes, and enhanced phagocytic, respiratory
      burst, lysozyme, bactericidal and anti-protease activities compared with the
      controls.

PMID- 19843198
TI  - The acceptability to stakeholders of mandatory nutritional labelling in France
      and the UK--findings from the PorGrow project.
AB  - BACKGROUND: Implementing a European Union (EU)-wide mandatory nutrition labelling
      scheme has been advocated as part a multi-pronged strategy to tackle obesity. The
      type of scheme needs to be acceptable to all key stakeholders. This study
      explored stakeholders' viewpoints of labelling in two contrasting food cultures
      (France and the UK) to see whether attitudes were influenced by sectoral
      interests and/or national context. METHODS: Using Multi Criteria Mapping, a
      decision analysis tool that assesses stakeholder viewpoints, quantitative and
      qualitative data were gathered during tape-recorded interviews. In France and the
      UK, 21 comparable stakeholders appraised nutritional labelling with criteria of
      their own choosing (i.e. feasibility, societal benefits, social acceptability,
      efficacy in addressing obesity, additional health benefits) and three criteria
      relating to cost (to industry; public sector; individuals). When scoring,
      interviewees provided both optimistic (best case) and pessimistic (worst case)
      judgements. RESULTS: Overall, mandatory nutritional labelling was appraised least
      favourably in France. Labelling performed worse under optimistic (best case)
      scenarios in France, for five out of eight sets of criteria. French stakeholders
      viewed labelling as expensive, having fewer benefits to society and as being
      marginally less effective than UK stakeholders did. However, French interviewees
      thought implementing labelling was feasible and would provide additional health
      benefits. British and French stakeholders made similar quantitative judgements on
      how socially acceptable mandatory labelling would be. CONCLUSIONS: There is
      agreement between some stakeholder groups in the two different countries,
      especially food chain operators. However, cultural differences emerged that could
      influence the impact of an EU-wide mandatory labelling scheme in both countries.

PMID- 19843199
TI  - Implementation of an electromagnetic imaging system to facilitate nasogastric and
      post-pyloric feeding tube placement in patients with and without critical
      illness.
AB  - BACKGROUND: Artificial nutrition support is required to optimise nutritional
      status in many patients. Traditional methods of placing feeding tubes may incur
      clinical risk and financial costs. A technique facilitating placement of
      nasogastric and post-pyloric tubes via electromagnetic visual guidance may reduce
      the need for X-ray exposure, endoscopy time and the use of parenteral nutrition.
      The present study aimed to audit use of such a system at initial implementation
      in patients within an acute NHS Trust. METHODS: A retrospective review was
      undertaken of dietetic and medical records for the first 14 months of using the
      Cortrak system. Data were collected on referral origin, preparation of the
      patient prior to insertion, placement success rates and need for X-ray. Cost
      analysis was also performed. RESULTS: Referrals were received from primary
      consultants or consultant intensivists, often on the advice of the dietitian.
      Fifty-nine percent of patients received prokinetic therapy at the time of
      placement. Thirty-nine tube placements were attempted. Sixty-nine percent of
      referrals for post-pyloric tube placement resulted in successful placement. X-ray
      films were requested for 22% of all attempted post-pyloric placements. Less than
      half of nasogastric tubes were successfully passed, although none of these
      required X-ray confirmation. The mean cost per tube insertion attempt was 111
      pounds. CONCLUSIONS: This system confers advantages, particularly in terms of
      post-pyloric tube placement, even at this early stage of implementation. A
      reduction in clinical risk and cost avoidance related to X-ray exposure, the need
      for endoscopic tube placement and parenteral nutrition have been achieved. The
      implementation of this system should be considered in other centres.

PMID- 19843200
TI  - Feeding strategies used by primary school meal staff and their impact on
      children's eating.
AB  - BACKGROUND: In parent-child interactions, feeding strategies including pressure,
      restriction, modelling, rewards, encouragement and repeated taste exposure have
      been reliably shown to influence children's eating. Because there is no evidence
      that the psychosocial interactions inherent in the strategies are context
      dependent, the present study investigated their utilisation during primary school
      meal supervision. METHODS: A case study of one Local Authority in Wales was
      conducted involving eleven primary schools stratified into socio-economic
      quartiles. Focussed observations were carried out over two to three lunchtimes
      per school to explore the feeding strategies, outcomes and behaviours inherent in
      the dining hall context. These were supplemented by semi-structured interviews
      with catering staff and midday supervisors, which were carried out after the
      observation session. RESULTS: Most feeding strategies used by school meal staff
      reflected those reported in the literature (e.g. pressure, encouragement and
      rewards), although purposeful modelling of eating behaviours was not found and
      the imposition of food norms, such as eating dessert last, was common. Dining
      hall staff readily, if not consistently, used these strategies, although the
      constraints and opportunities of each dining hall context influenced their
      selection and implementation. However, even if children left the service point
      with nutritionally balanced meals, they often failed to eat them. CONCLUSIONS:
      Because repeated taste exposure is known to increase liking for foods, further
      studies are recommended to investigate how the naturally occurring feeding
      strategies evident in primary school dining halls could be harnessed to encourage
      children to taste the nutritionally balanced schools meals that school meal
      transformation programmes will expose them to.

PMID- 19843201
TI  - Dietary Approaches to Stop Hypertension (DASH) diet: applicability and
      acceptability to a UK population.
AB  - BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is widely
      promoted in the USA for the prevention and treatment of high blood pressure. It
      is high in fruit and vegetables, low-fat dairy and wholegrain foods and low in
      saturated fat and refined sugar. To our knowledge, the use of this dietary
      pattern has not been assessed in a free-living UK population. METHODS: The DASH
      diet was adapted to fit UK food preferences and portion sizes. Fourteen healthy
      subjects followed the adapted DASH diet for 30 days in which they self-selected
      all food and beverages. Dietary intake was assessed by 5-day food diaries
      completed before and towards the end of the study. Blood pressure was measured at
      the beginning and end of the study to assess compliance to the DASH style diet.
      RESULTS: The DASH diet was easily adapted to fit with UK food preferences.
      Furthermore, it was well tolerated and accepted by subjects. When on the DASH
      style diet, subjects reported consuming significantly (P < 0.01) more
      carbohydrate and protein and less total fat (5%, 6% and 9% total energy,
      respectively). Sodium intakes decreased by 860 mg day(-1) (P < 0.001). Systolic
      and diastolic blood pressure decreased significantly (P < 0.05) by 4.6 and 3.9
      mmHg, respectively when on the DASH style diet. CONCLUSIONS: The DASH style diet
      was well accepted and was associated with a decrease in blood pressure in
      normotensive individuals and should be considered when giving dietary advice to
      people with elevated blood pressure in the UK.

PMID- 19843202
TI  - Presence of impaired intestinal calcium absorption in chronic hypovitaminosis D
      and its change after cholecalciferol supplementation: assessment by the calcium
      load test.
AB  - BACKGROUND: Hypovitaminosis D is common in Asian Indians and its functional
      significance is currently under investigation. Previous studies have reported on
      the effect of low serum 25(OH)D levels (<50 nmol L(-1)) on bone mineral density
      and serum parathyroid hormone values. The present study assessed the effect of
      chronic hypovitaminosis D in Asian Indians on intestinal calcium absorption and
      its change after cholecalciferol supplementation. METHODS: Subjects included 29
      healthy volunteers [mean (SD) age, 28.4 +/- 6.4 years] with low serum 25(OH)D
      levels on screening. Intestinal calcium absorption was assessed by the 'calcium
      load test' with 1 g of oral elemental calcium. Subjects were put on a calcium
      restricted diet 1 week prior to the test. The calcium load test was repeated in
      26 of them after 8 weeks of supplementation with oral cholecalciferol (60 000 IU
      week(-1)). RESULTS: The mean urinary calcium/creatinine ratio of the study
      subjects was 0.027 +/- 0.023 mg mg(-1) under fasting conditions and increased to
      0.035 +/- 0.032 mg mg(-1) after calcium loading (delta change = 29.6%, P = 0.33).
      After 8 weeks of cholecalciferol supplementation, the mean serum 25(OH)D
      increased from 18.9 +/- 11.9 to 84.4 +/- 34.9 nmol L(-1) (P < 0.0001).
      Concomitantly, the mean urinary calcium/creatinine ratio of the study subjects
      increased from 0.030 +/- 0.024 mg mg(-1) under fasting conditions to 0.059 +/-
      0.045 mg mg(-1) after calcium loading (delta change = 96.6%, P = 0.008).
      CONCLUSIONS: The results obtained in the present study show that chronic
      hypovitaminosis D in Asian Indians has functional relevance in terms of its
      effect on intestinal calcium absorption, which improves with cholecalciferol
      supplementation. These findings support the need for improving the vitamin D
      status of Asian Indians through dietary supplementation and exposure to sunshine.

PMID- 19843203
TI  - Immediate and long-term outcome of redo percutaneous mitral valvuloplasty:
      comparison with initial procedure in patients with rheumatic mitral restenosis.
AB  - AIMS: We explored the immediate and long-term outcome of redo percutaneous mitral
      valvuloplasty (PMV) in a series of patients with mitral restenosis in comparison
      with initial PMV in the same series. METHODS: We enrolled 40 consecutive patients
      presenting with mitral restenosis after successful initial PMV. Redo PMV was
      performed by the antegrade transseptal approach using either the Inoue technique
      or the multitrack technique. Reassessment by transthoracic echocardiography was
      repeated 48 hours later, and annually thereafter. Procedural success was defined
      as 50% or more increase of mitral valve area (MVA) with a final MVA >or=1.5
      cm(2), without major complications. Restenosis was defined as loss of >50% of the
      initial gain of MVA by the preceding PMV with a final MVA <1.5 cm(2). RESULTS:
      Procedural success was achieved in 37 (92.5%) patients. Both the initial and redo
      procedures were similar concerning the final MVA and mean transmitral pressure
      gradient (P > 0.05 for all). The gain of MVA was higher in the initial as
      compared to the redo procedure (P < 0.001). The initial mitral valve score
      correlated negatively with the final MVA in both the initial and redo procedures,
      and was the only independent predictor of the time to redo procedure, by
      multivariate regression analysis. At long-term follow-up (61 +/- 2.8 months), the
      mean MVA was 1.6 +/- 0.3 cm(2). Three patients--out of 12 available for follow-up
      -developed restenosis. CONCLUSION: Redo PMV for mitral restenosis is feasible,
      safe, and achieves immediate and long-term outcome comparable to initial PMV.

PMID- 19843204
TI  - Characterization of cerebrospinal fluid monoamine metabolites in peripubertal
      chimpanzees (Pan troglodytes).
AB  - BACKGROUND: Assessment of cerebrospinal (CSF) monoamine metabolites 5
      hydroxyindoeacetic acid (5-HIAA) and homovanillic acid (HVA), and the serotonin
      precursor tryptophan (TRP), in chimpanzees may help in understanding the
      neurobiology underlying aggressive, impulsive behavior in humans and non-human
      primates. METHODS: Two CSF samples were obtained from 11 peripubertal chimpanzees
      8 months apart and were assayed for monoamine metabolite and TRP concentrations.
      RESULTS: Substantial inter-individual stability was observed for 5-HIAA (n = 11;
      r = 0.83, P < 0.001) and HVA (r = 0.91, P < 0.001). Females had significantly
      higher concentrations of 5-HIAA compared to males (F(1,8) = 7.31; P < 0.05).
      Levels of 5-HIAA (r = -0.62, P < 0.05), HVA (r = -0.86, P < 0.001) and TRP levels
      (r = -0.67; P < 0.05) decreased with age. CONCLUSION: Close parallels were
      observed between chimpanzees and humans with respect to absolute levels, sex
      effects, ontogeny, and 5-HIAA-HVA correlations, supporting the potential utility
      of the measures in understanding relationships between monoamine functioning and
      behavior in chimpanzees and humans.

PMID- 19843205
TI  - Persistence of Escherichia coli O157:H7 on the rhizosphere and phyllosphere of
      lettuce.
AB  - AIMS: The major objective of this study was to determine the effects of low
      levels of Escherichia coli O157:H7 contamination on plant by monitoring the
      survival of the pathogen on the rhizosphere and leaf surfaces of lettuce during
      the growth process. METHODS AND RESULTS: Real-time PCR and plate counts were used
      to quantify the survival of E. coli O157:H7 in the rhizosphere and leaf surfaces
      after planting. Real-time PCR assays were designed to amplify the stx1, stx2 and
      the eae genes of E. coli O157:H7. The detection limit for E. coli O157:H7
      quantification by real-time PCR was 2.4 x 10(3) CFU g(-1) of starting DNA in
      rhizosphere and phyllosphere samples and about 10(2) CFU g(-1) by plate count.
      The time for pathogens to reach detection limits on the leaf surface by plate
      counts was 7 days after planting in comparison with 21 days in the rhizosphere.
      However, real-time PCR continued to detect stx1, stx2 and the eae genes
      throughout the experimental period. CONCLUSION: Escherichia coli O157:H7 survived
      throughout the growth period as was determined by real-time PCR and by subsequent
      enrichment and immunomagnetic separation of edible part of plants. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The potential presence of human pathogens in vegetables
      grown in soils contaminated with E. coli O157:H7 is a serious problem to our
      national food supply as the pathogen may survive on the leaf surface as they come
      in contact with contaminated soil during germination.

PMID- 19843206
TI  - The emerging methicillin-resistant Staphylococcus aureus ST398 clone can easily
      be typed using the Cfr9I SmaI-neoschizomer.
AB  - AIM: To establish a PFGE protocol using Cfr9I, neoschizomer of SmaI, for typing
      of Staphylococcus aureus isolates belonging to the emerging MRSA ST398 clone.
      METHODS AND RESULTS: Staphylococcus aureus ST398 and non-ST398 isolates were
      analysed using the PFGE conditions recommended by the HARMONY consensus protocol.
      Genomic DNA of non-ST398 isolates could be digested with SmaI, XmaI (also a SmaI
      neoschizomer) and Cfr9I. The DNA of SmaI-nontypeable ST398 isolates was partially
      resistant to XmaI, but could be digested with Cfr9I. By PCR
      amplification/sequencing, the presence of a novel C5-cytosine methyltransferase
      gene (sauST398M) was detected in the ST398 isolates. The encoded enzyme, which
      shows high similarity with C5-cytosine methyltransferases that modify the CCCGGG
      recognition sequence, could be responsible for the different restriction results.
      CONCLUSION: SmaI-PFGE is regarded as the 'gold standard' for typing S. aureus.
      Because of different susceptibility of the GGGCCC recognition sites of the ST398
      DNA against SmaI, XmaI and Cfr9I, the proposed protocol is a valuable tool for
      ST398 typing. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of this protocol
      allows the comparison of results from SmaI-nontypeable isolates with S. aureus
      SmaI-PFGE databases and can be applied for outbreak investigations and
      traceability studies of this emerging MRSA clone.

PMID- 19843207
TI  - In vitro antiviral activity of Melaleuca alternifolia essential oil.
AB  - AIMS: To investigate the in vitro antiviral activity of Melaleuca alternifolia
      essential oil (TTO) and its main components, terpinen-4-ol, alpha-terpinene,
      gamma-terpinene, p-cymene, terpinolene and alpha-terpineol. METHODS AND RESULTS:
      The antiviral activity of tested compounds was evaluated against polio type 1,
      ECHO 9, Coxsackie B1, adeno type 2, herpes simplex (HSV) type 1 and 2 viruses by
      50% plaque reduction assay. The anti-influenza virus assay was based on the
      inhibition of the virus-induced cytopathogenicity. Results obtained from our
      screening demonstrated that the TTO and some of its components (the terpinen-4
      ol, the terpinolene, the alpha-terpineol) have an inhibitory effect on influenza
      A/PR/8 virus subtype H1N1 replication at doses below the cytotoxic dose. The
      ID(50) value of the TTO was found to be 0.0006% (v/v) and was much lower than its
      CD(50) (0.025% v/v). All the compounds were ineffective against polio 1, adeno 2,
      ECHO 9, Coxsackie B1, HSV-1 and HSV-2. None of the tested compounds showed
      virucidal activity. Only a slight virucidal effect was observed for TTO (0.125%
      v/v) against HSV-1 and HSV-2. CONCLUSIONS: These data show that TTO has an
      antiviral activity against influenza A/PR/8 virus subtype H1N1 and that antiviral
      activity has been principally attributed to terpinen-4-ol, the main active
      component. SIGNIFICANCE AND IMPACT OF THE STUDY: TTO should be a promising drug
      in the treatment of influenza virus infection.

PMID- 19843208
TI  - Rapid identification of bacterial isolates from aqueous kava (Piper methysticum)
      extracts by polymerase chain reaction and DNA sequencing.
AB  - AIM: Fresh kava beverages have a limited shelf life under refrigerated
      conditions. The objective of this study was to isolate and identify bacteria in
      aqueous extracts of kava rhizome. METHODS AND RESULTS: The internal part of kava
      rhizome was used to minimize soil contamination. Three kava extracts were
      prepared, serially diluted and plated on nutrient agar. Isolated colonies were
      identified by sequencing polymerase chain reaction amplicons targeting the
      eubacterial 16S rDNA and the tuf gene of Staphylococcus. Seventy-five bacterial
      isolates belonged to 16 genera. Bacillus, Cellulomonas, Enterococcus,
      Pectobacterium and Staphylococcus were identified in all kava extracts.
      CONCLUSIONS: Kava rhizome contains large amounts of starch and fibre, which
      justify the presence of polysaccharide-degrading bacteria in the extracts.
      Bacillus cereus group and Staphylococcus species may produce toxins and cause
      foodborne illness. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this
      study provide fundamental information that may be used to enhance the microbial
      quality and safety of kava beverages.

PMID- 19843209
TI  - Enhanced biotransformation of TCE using plant terpenoids in contaminated
      groundwater.
AB  - AIMS: To examine plant terpenoids as inducers of TCE (trichloroethylene)
      biotransformation by an indigenous microbial community originating from a plume
      of TCE-contaminated groundwater. METHODS AND RESULTS: One-litre microcosms of
      groundwater were spiked with 100 micromol 1(-1) of TCE and amended weekly for 16
      weeks with 20 microl 1(-1) of the following plant monoterpenes: linalool,
      pulegone, R-(+) carvone, S-(-) carvone, farnesol, cumene. Yeast extract-amended
      and unamended control treatments were also prepared. The addition of R-carvone
      and S-carvone, linalool and cumene resulted in the biotransformation of upwards
      of 88% of the TCE, significantly more than the unamendment control (61%). The
      aforementioned group of terpenes also significantly (P < 0.05) allowed more TCE
      to be degraded than the remaining two terpenes (farnesol and pulegone), and the
      yeast extract treatment which biotransformed 74-75% of the TCE. The microbial
      community profile was monitored by denaturing gradient gel electrophoresis and
      demonstrated much greater similarities between the microbial communities in
      terpene-amended treatments than in the yeast extract or unamended controls.
      CONCLUSIONS: TCE biotransformation can be significantly enhanced through the
      addition of selected plant terpenoids. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Plant terpenoid and nutrient supplementation to groundwater might provide an
      environmentally benign means of enhancing the rate of in situ TCE bioremediation.

PMID- 19843210
TI  - Histopathological studies of sclerotia of Rhizoctonia solani parasitized by the
      EGFP transformant of Trichoderma virens.
AB  - AIMS: The aim of the study was to investigate the antagonistic interactions of
      Trichoderma species against Rhizoctonia solani sclerotia by enhanced green
      fluorescence protein (EGFP)-tagged transformant of Trichoderma virens TY009.
      METHODS AND RESULTS: An EGFP was used as a report gene for transforming T. virens
      strain, and a stable EGFP transformant GF5 was obtained with the mycoparasitic
      activity against sclerotia of R. solani. Observation of parasitized sclerotia by
      fluorescence microscopy showed hyphae of transformant GF5 was able to invade into
      sclerotia and its colonization was mainly intercellar with uniformly distributed
      mycelium in sclerotia. The host cells were colonized, penetrated, and then the
      whole cells were replaced by transformant GF5 hyphae. Chlamydospores were seen
      after 10 days but mature ones after 20 days. Sclerotia became soft and decayed
      after 40 days but a few cells seemed not to be colonized completely. CONCLUSIONS:
      Trichoderma virens was able to parasitize sclerotia to make sclerotia soft and
      decayed, and its colonization was mainly intercellar in sclerotial tissues.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is first report of parasitism of
      sclerotia of R. solani by EGFP-tagged transformant, providing useful information
      for using T. virens as effective biocontrol agent.

PMID- 19843211
TI  - Comparison of in vitro models to study bacterial adhesion to the intestinal
      epithelium.
AB  - AIMS: To evaluate the adhesion ability of intestinal bacteria to different in
      vitro models of intestinal epithelia, and to estimate the suitability of these
      models and the type of interactions involved. METHODS AND RESULTS: The adhesion
      of probiotic (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp.
      lactis Bb12), commensal (B. animalis IATA-A2 and B. bifidum IATA-ES2) and
      potentially pathogenic bacteria (E. coli and L. monocytogenes) was determined.
      The adhesion models used were polycarbonate-well plates, with or without mucin,
      and different configurations of Caco-2 and/or HT29-MTX cell cultures. All
      bacteria adhered to wells without mucin (2.6-27.3%), the values being highly
      variable depending on the bacterial strain. Adhesion percentages of potentially
      probiotic bacteria to Caco-2 cultures were remarkably lower (P < 0.05) than those
      to mucin, and more similar to those of pathogenic strains. The lowest adhesion of
      different bacterial strains was detected on HT29-MTX (0.5-2.3%) cultures and Caco
      2/HT29-MTX (0.6-3.2%) cocultures, while these values were increased in Caco-2
      cultures plus mucin. CONCLUSIONS: The results suggested that bacterial strains
      exhibit different capacities to adhere to cellular components and several types
      of mucin present in different models, showing preferences for intestinal MUC2.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The use of Caco-2 cells monolayer plus
      mucin (type II) better approaches the physiological characteristics of in vivo
      situation, providing a reliable and suitable in vitro model to evaluate bacterial
      adhesion.

PMID- 19843212
TI  - The presence of prtP proteinase gene in natural isolate Lactobacillus plantarum
      BGSJ3-18.
AB  - AIMS: The study of proteolytic activity and examination of proteinase gene region
      organization in proteolytically active Lactobacillus plantarum strains from
      different natural sources. METHODS AND RESULTS: A set of 37 lactobacilli was
      distinguished by using multiplex PCR assay. Results showed that 34 strains were
      Lact. plantarum and three of them were Lact. paraplantarum. The examination of
      proteolytic activity revealed that 28 Lact. plantarum and two Lact. paraplantarum
      hydrolyse beta-casein. Further analyses of all proteolytically active Lact.
      plantarum with primers specific for different types of CEPs demonstrated that
      strain BGSJ3-18 has prtP catalytic domain as well as prtP-prtM intergenic region
      showing more than 95% sequence identity with the same regions present in Lact.
      paracasei, Lact. casei and L. lactis. No presence of prtB, prtH or prtR
      proteinase genes was detected in any of tested Lact. plantarum strains.
      CONCLUSIONS: One out of 28 analysed Lact. plantarum strains harbours the prtP
      like gene. The other proteolytically active Lact. plantarum probably possesses a
      different type of extracellular proteinase(s). SIGNIFICANCE AND IMPACT OF THE
      STUDY: It is the first report about the presence of the prtP-like gene in Lact.
      plantarum, which illustrates the mobility of this gene and its presence in
      different species.

PMID- 19843213
TI  - Effect of oral immunization with Aeromonas hydrophila ghosts on protection
      against experimental fish infection.
AB  - AIMS: To investigate whether oral immunization with Aeromonas hydrophila ghosts
      (AHG) vaccine can elicit mucosal and systemic immune responses of Carp (Carassius
      auratus gibelio) compared to conventional formalin-killed bacteria (FKC). METHODS
      AND RESULTS: Fish were fed diets coated with AHG, FKC or phosphate buffered
      saline (PBS) alone, after immunization, more antigen-specific antibody was
      significantly detected in serum and intestinal mucus in AHG group than FKC group
      and PBS group. In addition, after challenged with the parent strain J-1, the
      survival of bacterial ghost-vaccinated fish was higher than PBS group and FKC
      group, the relative per cent survival (RPS) being 76.8%, 58.9%, respectively.
      CONCLUSIONS: Oral immunization with A. hydrophila ghosts can elicit systemic and
      mucosal adaptive immune responses and has higher potential to induce protective
      adaptive immunity than normal vaccine. SIGNIFICANCE AND IMPACT OF THE STUDY: Oral
      immunization with bacterial ghosts is a promising new solution with potential
      application to prevent diseases in fish.

PMID- 19843214
TI  - Effects of chlorophyllin on replication of poliovirus and bovine herpesvirus in
      vitro.
AB  - AIMS: Chlorophyllin (CHLN), a synthetic derivative of chlorophyll, was assayed in
      the replication of poliovirus (PV-1) and bovine herpesvirus (BoHV-1) in HEp-2
      cell cultures. METHODS AND RESULTS: Virucidal activity of CHLN was evaluated and
      the time-of-addition assay was performed as follows: before the infection (-1 and
      -2 h), at the time of the infection (0 h) and after the infection (1 and 2 h).
      Plaque reduction assay (PRA) showed that CHLN inhibited BoHV-1 and PV-1 infection
      and the 50% inhibitory concentrations (IC(50)) against BoHV-1 and PV-1 infection
      were 8.6 and 19.8 microg ml(-1), respectively. The time-of-addition study
      demonstrated that the CHLN was effective inhibiting viral replication in 51% and
      66.5% for PV-1 and BoHV-1, respectively, at the highest concentration of 20.0
      microg ml(-1), when added during the infection. The directed effect of CHLN on
      viral strains demonstrated an inhibition of 62% and 66.4% for PV-1 and BoHV-1,
      respectively, by PRA. CONCLUSIONS: These results demonstrated that CHLN could be
      used as an antiviral suggesting directed activity on virus particles and on virus
      receptor sites to BoHV. For poliovirus, CHLN also demonstrated virucide activity,
      moreover, showed to inhibit early steps of the replication cycle. SIGNIFICANCE
      AND IMPACT OF THE STUDY: CHLN demonstrated promising selectivity index for both
      virus strains; therefore, it can be used for the development of an antiviral
      agent.

PMID- 19843215
TI  - Copper and cadmium: responses in Pseudomonas putida KT2440.
AB  - AIMS: To compare responses of a soil bacterium to Cu and Cd. METHODS AND RESULTS:
      In minimal medium, Cd caused a dose-dependent growth stasis of logarithmic phase
      cells of Pseudomonas putida, strain KT2440, whereas Cu did not compromise growth
      up to 10 mg l(-1). Proteomics showed changes in accumulation of both membrane and
      soluble proteins by 6 h of treatment; increased Krebs cycle enzymes were
      apparent. Transcript analysis showed Cd- and Cu-induced different genes. Cd
      induced genes encoding the transcriptional regulator CzrR2; an outer membrane
      protein associated with lipopolysaccharide stability, H1; two oxidative stress
      protective proteins and the P-type ATPase, CadA2, associated with Cd(2+) efflux.
      The genes most responsive to Cu encoded the regulator CopR1 and the outer
      membrane resistance protein regulated by CopR1, CopB1; a putative porin, PorD and
      the Cu-binding protein, PacZ or CopZ, and CopA2. CONCLUSIONS: These findings
      support that a soil pseudomonad restricts internalization of the metals by using
      different sets of binding proteins and efflux pumps. Activation of mechanisms to
      protect against oxidative stress also was evident especially with Cd exposure.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The differential cellular responses to Cd
      and Cu suggest that risk assessment for Cd and Cu should be different.

PMID- 19843216
TI  - High-resolution architecture of the outer membrane of the Gram-negative bacteria
      Roseobacter denitrificans.
AB  - The outer membrane of Gram-negative bacteria protects the cell against
      bactericidal substances. Passage of nutrients and waste is assured by outer
      membrane porins, beta-barrel transmembrane channels. While atomic structures of
      several porins have been solved, so far little is known on the supramolecular
      structure of the outer membrane. Here we present the first high-resolution view
      of a bacterial outer membrane gently purified maintaining remnants of
      peptidoglycan on the perisplasmic surface. Atomic force microscope images of
      outer membrane fragments of the size of approximately 50% of the bacterial
      envelope revealed that outer membrane porins are by far more densely packed than
      previously assumed. Indeed the outer membrane is a molecular sieve rather than a
      membrane. Porins cover approximately 70% of the membrane surface and form locally
      regular lattices. The potential role of exposed aromatic residues in the
      formation of the supramolecular assembly is discussed. Finally, we present first
      structural data of the outer membrane porin from the marine Gram-negative
      bacteria Roseobacter denitrificans, and we perform a sequence alignment with
      porins of known structure.

PMID- 19843217
TI  - Differential substrate specificity of group I and group II chaperonins in the
      archaeon Methanosarcina mazei.
AB  - Chaperonins are macromolecular machines that assist in protein folding. The
      archaeon Methanosarcina mazei has acquired numerous bacterial genes by horizontal
      gene transfer. As a result, both the bacterial group I chaperonin, GroEL, and the
      archaeal group II chaperonin, thermosome, coexist. A proteome-wide analysis of
      chaperonin interactors was performed to determine the differential substrate
      specificity of GroEL and thermosome. At least 13% of soluble M. mazei proteins
      interact with chaperonins, with the two systems having partially overlapping
      substrate sets. Remarkably, chaperonin selectivity is independent of phylogenetic
      origin and is determined by distinct structural and biochemical features of
      proteins. GroEL prefers well-conserved proteins with complex alpha/beta domains.
      In contrast, thermosome substrates comprise a group of faster-evolving proteins
      and contain a much wider range of different domain folds, including small all
      alpha and all-beta modules, and a greater number of large multidomain proteins.
      Thus, the group II chaperonins may have facilitated the evolution of the highly
      complex proteomes characteristic of eukaryotic cells.

PMID- 19843218
TI  - Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA
      polymerase.
AB  - The prototypic Y family DNA polymerase IV (PolIV) of Escherichia coli is involved
      in multiple replication-associated processes including spontaneous mutagenesis,
      translesion synthesis (TLS), cell fitness, survival under stressful conditions
      and checkpoint like functions. It interacts physically and functionally with the
      replisome's beta processivity clamp through the canonical PolIV C-terminal
      peptide (CTP). A second interaction that involves a portion of the little finger
      (LF) domain of PolIV has been structurally described. Here we show that the LF
      beta interaction stabilizes the clamp-polymerase complex in vitro and is
      necessary for the access of PolIV to ongoing replication forks in vivo. However,
      in contrast to the CTP-beta, the LF-beta interaction is dispensable for the role
      of the polymerase in TLS. This discloses two independent modes of action for
      PolIV and, in turn, uncovers a novel way by which the cell may regulate the
      potentially deleterious effect of such low fidelity polymerases during
      replication.

PMID- 19843219
TI  - Dual control by perfectly overlapping sigma 54- and sigma 70- promoters adjusts
      small RNA GlmY expression to different environmental signals.
AB  - In Escherichia coli synthesis of glucosamine-6-phosphate synthase GlmS is
      feedback-controlled by a regulatory cascade composed of small RNAs GlmY and GlmZ.
      When GlcN6P becomes limiting, GlmY accumulates and inhibits processing of GlmZ.
      Full-length GlmZ base-pairs with the glmS transcript and activates synthesis of
      GlmS, which re-synthesizes GlcN6P. Here we show that glmY expression is
      controlled by two overlapping promoters with the same transcription start site. A
      sigma(70)-dependent promoter contributes to glmY transcription during exponential
      growth. Alternatively, glmY can be transcribed from a sigma(54)-dependent
      promoter, which requires the YfhK/YfhA two-component system for activity. YfhK is
      a sensor kinase and YfhA is a response regulator that contains a sigma(54)
      interaction domain. YfhA binds to a DNA region located more than 100 bp upstream
      of glmY. Three copies of the conserved sequence TGTCN(10)GACA contribute to
      binding, and the two sites next to glmY are essential for activation of the
      sigma(54)-dependent promoter by YfhA. YfhK and YfhA upregulate GlmY when cells
      enter the stationary growth phase, whereas regulation by glucosamine-6-phosphate
      occurs post GlmY transcription. Target genes regulated by YfhK and YfhA were
      unknown so far. We propose to rename these proteins to GlrK and GlrR, for glmY
      regulating kinase and response regulator respectively.

PMID- 19843220
TI  - Functional stratification of the Spitzenkorper of Neurospora crassa.
AB  - GS-1 (ncu04189) is a protein required for the synthesis of beta-1,3-glucan in
      Neurospora crassa. As chitin, beta-1,3-glucan is a morphogenetically relevant
      component of the fungal cell wall. Previously, we showed that chitin synthases
      are delivered to the growing hyphal tip of N. crassa by secretory microvesicles
      that follow an unconventional route and accumulate in the core of the
      Spitzenkorper (Spk). Tagged with the green fluorescent protein (GFP), GS-1
      accumulated in the hyphal apex forming a dynamic and pleomorphic ring-like
      structure ('Spitzenring') that corresponded to the Spk outer macrovesicular
      stratum and surrounded the inner core of chitin synthase-containing
      microvesicles. TIRF microscopy revealed that GS-1-GFP reached the hyphal apex as
      a population of heterogeneous-size particles that moved along defined paths. On
      sucrose density gradients, GS-1-associated particles mainly sedimented in a high
      density range 1.1272-1.2124 g ml(-1). Clearly, GS-1 and chitin synthases of N.
      crassa are contained in two different types of secretory vesicles that accumulate
      in different strata of the Spk, a differentiation presumably related to the
      spatial control of cell-wall synthesis.

PMID- 19843221
TI  - Direct activator/co-activator interaction is essential for bacteriophage T4
      middle gene expression.
AB  - The bacteriophage T4 AsiA protein is a bifunctional regulator that inhibits
      transcription from the major class of bacterial promoters and also serves as an
      essential co-activator of transcription from T4 middle promoters. AsiA binds the
      primary s factor in Escherichia coli, sigma(70), and modifies the promoter
      recognition properties of the sigma(70)-containing RNA polymerase(RNAP)
      holoenzyme. In its role as co-activator, AsiA directs RNAP to T4 middle promoters
      in the presence of the T4-encoded activator MotA. According to the current model
      for T4 middle promoter activation, AsiA plays an indirect role in stabilizing the
      activation complex by facilitating interaction between DNA-bound MotA and
      sigma(70). Here we show that AsiA also plays a direct role in T4 middle promoter
      activation by contacting the MotA activation domain. Furthermore,we show that
      interaction between AsiA and the beta-flap domain of RNAP is important for co
      activation. Based on our findings, we propose a revised model for T4 middle
      promoter activation, with AsiA organizing the activation complex via three
      distinct protein-protein interactions.

PMID- 19843222
TI  - Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side
      chain degradation in Rhodococcus jostii RHA1.
AB  - The cyp125 gene of Rhodococcus jostii RHA1 was previously found to be highly
      upregulated during growth on cholesterol and the orthologue in Mycobacterium
      tuberculosis (rv3545c) has been implicated in pathogenesis. Here we show that
      cyp125 is essential for R. jostii RHA1 to grow on 3-hydroxysterols such as
      cholesterol, but not on 3-oxo sterol derivatives, and that CYP125 performs an
      obligate first step in cholesterol degradation. The involvement of cyp125 in
      sterol side-chain degradation was confirmed by disrupting the homologous gene in
      Rhodococcus rhodochrous RG32, a strain that selectively degrades the cholesterol
      side-chain. The RG32 Omega cyp125 mutant failed to transform the side-chain of
      cholesterol, but degraded that of 5-cholestene-26-oic acid-3beta-ol, a
      cholesterol catabolite. Spectral analysis revealed that while purified ferric
      CYP125(RHA1) was < 10% in the low-spin state, cholesterol (K(D)(app) = 0.20 +/-
      0.08 microM), 5 alpha-cholestanol (K(D)(app) = 0.15 +/- 0.03 microM) and 4
      cholestene-3-one (K(D)(app) = 0.20 +/- 0.03 microM) further reduced the low spin
      character of the haem iron consistent with substrate binding. Our data indicate
      that CYP125 is involved in steroid C26-carboxylic acid formation, catalysing the
      oxidation of C26 either to the corresponding carboxylic acid or to an
      intermediate state.

PMID- 19843223
TI  - Lateral FtsZ association and the assembly of the cytokinetic Z ring in bacteria.
AB  - Cell division in bacteria is facilitated by a polymeric ring structure, the Z
      ring, composed of tubulin-like FtsZ protofilaments. Recently it has been shown
      that in Bacillus subtilis, the Z ring forms through the cell cycle-mediated
      remodelling of a helical FtsZ polymer. To investigate how this occurs in vivo, we
      have exploited a unique temperature-sensitive strain of B. subtilis expressing
      the mutant protein FtsZ(Ts1). FtsZ(Ts1) is unable to complete Z ring assembly at
      49 degrees C, becoming trapped at an intermediate stage in the helix-to-ring
      progression. To determine why this is the case, we used a combination of methods
      to identify the specific defect of the FtsZ(Ts1) protein in vivo. Our results
      indicate that while FtsZ(Ts1) is able to polymerize normally into protofilaments,
      it is defective in the ability to support lateral associations between these
      filaments at high temperatures. This strongly suggests that lateral FtsZ
      association plays a crucial role in the polymer transitions that lead to the
      formation of the Z ring in the cell. In addition, we show that the FtsZ-binding
      protein ZapA, when overproduced, can rescue the FtsZ(Ts1) defect in vivo. This
      suggests that ZapA functions to promote the helix-to-ring transition of FtsZ by
      stimulating lateral FtsZ association.

PMID- 19843225
TI  - Identification and characterization of three novel EsaI/EsaR quorum-sensing
      controlled stewartan exopolysaccharide biosynthetic genes in Pantoea stewartii
      ssp. stewartii.

PMID- 19843224
TI  - Activation of sigma 28-dependent transcription in Escherichia coli by the cyclic
      AMP receptor protein requires an unusual promoter organization.
AB  - The Escherichia coli aer regulatory region contains a single promoter that is
      recognized by RNA polymerase containing the flagellar sigma factor, sigma(28).
      Expression from this promoter is dependent on direct activation by the cyclic AMP
      receptor protein, which binds to a target centred 49.5 base pairs upstream from
      the transcript start. Activator-dependent transcription from the aer promoter was
      reconstituted in vitro, and a tethered inorganic nuclease was used to find the
      position of the C-terminal domains of the RNA polymerase alpha subunits in
      transcriptionally competent open complexes. We report that the ternary activator-
      RNA polymerase--aer promoter open complex is organized differently from complexes
      at previously characterized promoters. Among other E. coli promoters recognized
      by RNA polymerase containing sigma(28), only the trg promoter is activated
      directly by the cyclic AMP receptor protein. The organization of the different
      promoter elements and the activator binding site at the trg promoter is the same
      as at the aer promoter, suggesting a common activation mechanism.

PMID- 19843226
TI  - Null mutations in Sinorhizobium meliloti exoS and chvI demonstrate the importance
      of this two-component regulatory system for symbiosis.
AB  - Exopolysaccharides, either succinoglycan or galactoglucan, are essential for the
      establishment of the symbiosis between Sinorhizobium meliloti and Medicago sativa
      (alfalfa). The ExoS/ChvI two-component regulatory system is known as a regulator
      of succinoglycan production but the genes that are directly regulated by ChvI
      have not been determined. Difficulty isolating exoS and chvI null mutants has
      prompted the suggestion that these genes are essential for S. meliloti viability.
      We have successfully isolated exoS and chvI null mutants using a merodiploid
      facilitated strategy. We present evidence that the S. meliloti ExoS/ChvI two
      component regulatory system is essential for symbiosis with alfalfa. Phenotypic
      analyses of exoS and chvI null mutant strains demonstrate that ExoS/ChvI controls
      both succinoglycan and galactoglucan production and is required for growth on
      over 21 different carbon sources. These new findings suggest that the ExoS/ChvI
      regulatory targets might not be the exo genes that are specific for succinoglycan
      biosynthesis but rather genes that have common influence on both succinoglycan
      and galactoglucan production. Other studied alpha-proteobacteria ExoS/ChvI
      orthologues are required for the bacteria to invade or persist in host cells and
      thus we present more evidence that this two-component regulatory system is
      essential for alpha-proteobacterial host interaction.

PMID- 19843227
TI  - The H-NS-like protein StpA represses the RpoS (sigma 38) regulon during
      exponential growth of Salmonella Typhimurium.
AB  - StpA is a paralogue of the nucleoid-associated protein H-NS that is conserved in
      a range of enteric bacteria and had no known function in Salmonella Typhimurium.
      We show that 5% of the Salmonella genome is regulated by StpA, which contrasts
      with the situation in Escherichia coli where deletion of stpA only had minor
      effects on gene expression. The StpA-dependent genes of S. Typhimurium are a
      specific subset of the H-NS regulon that are predominantly under the positive
      control of sigma(38) (RpoS), CRP-cAMP and PhoP. Regulation by StpA varied with
      growth phase; StpA controlled sigma(38) levels at mid-exponential phase by
      preventing inappropriate activation of sigma(38) during rapid bacterial growth.
      In contrast, StpA only activated the CRP-cAMP regulon during late exponential
      phase. ChIP-chip analysis revealed that StpA binds to PhoP-dependent genes but
      not to most genes of the CRP-cAMP and sigma(38) regulons. In fact, StpA
      indirectly regulates sigma(38)-dependent genes by enhancing sigma(38) turnover by
      repressing the anti-adaptor protein rssC. We discovered that StpA is essential
      for the dynamic regulation of sigma(38) in response to increased glucose levels.
      Our findings identify StpA as a novel growth phase-specific regulator that plays
      an important physiological role by linking sigma(38) levels to nutrient
      availability.

PMID- 19843228
TI  - Evidence that a secondary metabolic biosynthetic gene cluster has grown by gene
      relocation during evolution of the filamentous fungus Fusarium.
AB  - Trichothecenes are terpene-derived secondary metabolites produced by multiple
      genera of filamentous fungi, including many plant pathogenic species of Fusarium.
      These metabolites are of interest because they are toxic to animals and plants
      and can contribute to pathogenesis of Fusarium on some crop species. Fusarium
      graminearum and F. sporotrichioides have trichothecene biosynthetic genes (TRI)
      at three loci: a 12-gene TRI cluster and two smaller TRI loci that consist of one
      or two genes. Here, comparisons of additional Fusarium species have provided
      evidence that TRI loci have a complex evolutionary history that has included
      loss, non-functionalization and rearrangement of genes as well as trans-species
      polymorphism. The results also indicate that the TRI cluster has expanded in some
      species by relocation of two genes into it from the smaller loci. Thus,
      evolutionary forces have driven consolidation of TRI genes into fewer loci in
      some fusaria but have maintained three distinct TRI loci in others.

PMID- 19843229
TI  - Polyphosphate kinase 2: a modulator of nucleoside diphosphate kinase activity in
      mycobacteria.
AB  - Mycobacteria encode putative class II polyphosphate kinases (PPKs). We report
      that recombinant PPK2 of Mycobacterium tuberculosis catalyses the synthesis of
      GTP from GDP using polyphosphate rather than ATP as phosphate donor. Unlike that
      of PPK1, this is the favoured reaction of PPK2. The sites of autophosphorylation,
      H115 and H247, as well as G74 were critical for GTP-synthesizing activity.
      Compromised survival of a ppk2 knockout (PPK2-KO) of Mycobacterium smegmatis
      under heat or acid stress or hypoxia, and the ability of ppk2 of M. tuberculosis
      to complement this, confirmed that PPK2 plays a role in mycobacterial survival
      under stress. Intracellular ATP : GTP ratio was higher in PPK2-KO compared with
      the wild-type M. smegmatis, bringing to light a role of PPK2 in regulating the
      intracellular nucleotide pool. We present evidence that PPK2 does so by
      interacting with nucleoside diphosphate kinase (Ndk). Pull-down assays and
      analysis by surface plasmon resonance demonstrated that the interaction requires
      G74 of PPK2(MTB) and (109)LET(111) of Ndk(MTB). In summary, we unravel a novel
      mechanism of regulation of nucleotide pools in mycobacteria. Downregulation of
      ppk2 impairs survival of M. tuberculosis in macrophages, suggesting that PPK2
      plays an important role in the physiology of the bacteria residing within
      macrophages.

PMID- 19843231
TI  - Frank Kunst, 1943-2009.

PMID- 19843232
TI  - Immune reconstitution syndrome in a patient with disseminated histoplasmosis and
      steroid taper: maintaining the perfect balance.
AB  - Immune reconstitution syndrome (IRS) is an increasingly common condition that has
      been described in immunosuppressed individuals once immune function is restored.
      In this case, we describe a patient who had a renal transplant and subsequently
      developed pulmonary histoplasmosis. His course was also complicated by the
      development of a clinical syndrome that was originally attributed to
      thrombocytopenic thrombotic purpura (TTP). When he did not improve with
      plasmapheresis and high dose prednisone, a bone marrow biopsy revealed
      disseminated histoplasmosis and administration of prednisone was rapidly tapered.
      While on 5 mg of prednisone, he developed an inflammatory syndrome characterised
      by haemoptysis and respiratory distress, full work-up with pathology was
      consistent with immune reconstitution syndrome. Treatment for IRS consists of
      continuing treatment for the underlying infection and consideration of
      administering anti-inflammatory medication for supportive care. This syndrome
      should be considered in patients who develop worsening inflammatory symptoms
      while receiving appropriate treatment for their fungal infection in the setting
      of restoration of immune function.

PMID- 19843230
TI  - Role of Escherichia coli DNA polymerase I in chromosomal DNA replication
      fidelity.
AB  - We have investigated the possible role of Escherichia coli DNA polymerase (Pol) I
      in chromosomal replication fidelity. This was done by substituting the
      chromosomal polA gene by the polAexo variant containing an inactivated 3'-->5'
      exonuclease, which serves as a proofreader for this enzyme's misinsertion errors.
      Using this strain, activities of Pol I during DNA replication might be detectable
      as increases in the bacterial mutation rate. Using a series of defined lacZ
      reversion alleles in two orientations on the chromosome as markers for
      mutagenesis, 1.5- to 4-fold increases in mutant frequencies were observed. In
      general, these increases were largest for lac orientations favouring events
      during lagging strand DNA replication. Further analysis of these effects in
      strains affected in other E. coli DNA replication functions indicated that this
      polAexo mutator effect is best explained by an effect that is additive compared
      with other error-producing events at the replication fork. No evidence was found
      that Pol I participates in the polymerase switching between Pol II, III and IV at
      the fork. Instead, our data suggest that the additional errors produced by
      polAexo are created during the maturation of Okazaki fragments in the lagging
      strand.

PMID- 19843233
TI  - Pain following battlefield injury and evacuation: a survey of 110 casualties from
      the wars in Iraq and Afghanistan.
AB  - OBJECTIVE: Advances in regional anesthesia, specifically continuous peripheral
      nerve blocks (CPNBs), have greatly improved pain outcomes for wounded soldiers in
      Iraq and Afghanistan. pain management practice variations, however, do exist,
      depending on the availability of pain-trained military professionals deployed to
      combat support hospitals. an exploratory study was undertaken to examine pain and
      other outcomes during evacuation and at landstuhl regional medical center (lrmc),
      germany. DESIGN: a mixed-methods, semistructured interview survey design was
      conducted on a convenience sample of wounded u.s. soldiers evacuated from iraq
      and afghanistan to lrmc. setting and patients. a total of 110 wounded soldiers
      evacuated from IRAQ and Afghanistan from July 2007 to February 2008 completed a
      pain survey at LRMC. Data were collected on demographics, injury mechanism, last
      24-hour average, least, and worst, and pain now by using a 0-10 scale, and
      percent pain relief (from 0% [No relief] to 100% [Complete relief]). Similar
      items and measures of anxiety, distress, and worry during flight transport were
      measured (from 0 [None] to 10 [Extreme]). Responses were analyzed by using
      descriptive and correlational statistics, multiple linear regression, Mann
      Whitney U-tests, and t-tests. The Walter Reed Army Medical Center, Human Use
      Committee approved this investigation. RESULTS: Participants were typically male
      (99.1%), Caucasian (80%), and injured from improvised explosive devices (60%) and
      gunshots (21.8%). Average and worst pain scores were inversely correlated with
      pain relief during transport (r = -0.58 and r = -0.46, respectively; P < 0.001),
      and low to moderately positively correlated with increased anxiety, distress, and
      worry during transport (P < 0.05). Average percent pain relief achieved was 45.2%
      +/- 26.6% during transport and 64.5% +/- 23.5% while at LRMC (P < 0.001).
      Participants with CPNB catheters placed at LRMC reported significantly less pain
      right now (P = 0.031) and better pain relief (P = 0.029) than soldiers without
      CPNBs. CONCLUSIONS: Our findings underscore the value of early aggressive pain
      management after major combat injuries. Increased pain was associated with
      increased anxiety, distress, and worry during transport, suggesting the need for
      psychological management along with analgesia. Regional anesthesia techniques
      while at LRMC contributed to better pain outcomes.

PMID- 19843234
TI  - HHV-6 encephalitis in pediatric unrelated umbilical cord transplantation: a role
      for ganciclovir prophylaxis?
AB  - The role of ganciclovir as HHV-6 prophylaxis in unrelated HSCT setting remains
      controversial. We performed an eight-yr retrospective review of patients received
      unrelated HSCT from January 2000 to September 2008. From January 2002,
      ganciclovir prophylaxis 5 mg/kg twice daily for seven days for all unrelated HSCT
      before transplant was adopted. The prevalence of HHV-6 encephalitis was studied
      before and after the change in policy. Fifty-four unrelated HSCT were performed
      from January 2000 to September 2008. Four cases (7.4%) of HHV-6 encephalitis were
      diagnosed. All of them were due to variant B infection. Two cases out of 16 cases
      (12.5%) were diagnosed before adoption of the policy; two cases out of 38 cases
      (5.3%) were diagnosed afterward. All of them were unrelated UCB transplant
      recipients. They were all seropositive to HHV-6 before transplant. Two cases
      complicated with significant residual neurological deficit and refractory
      seizure. The other two cases died of other transplant-related mortalities. We
      conclude that HHV-6 encephalitis is still a rare complication of unrelated HSCT
      and may be more common in unrelated UCB transplant. Routine use of ganciclovir as
      HHV-6 prophylaxis in all unrelated HSCT recipients may not be justified but may
      have a role in unrelated UCB transplant.

PMID- 19843235
TI  - Chylopericardium in a child with impaired venous access following small bowel
      transplantation.
AB  - A 10-yr-old child with impaired venous access (bilateral occlusion of internal
      jugular veins, subclavian veins, and inominate veins) underwent an isolated small
      bowel transplant. He presented with lethargy, shortness of breath 13 months into
      his follow-up and was diagnosed to have chylopericardium. MR venography and
      lymphangiography could not demonstrate the site of lymphatic leak. His
      chyloperciardium was treated with pericardiocentesis and MCT diet. The most
      likely cause for the chylopericardium was venous occlusion of the subclavian
      veins with backpressure resulting in a lymphatic leak. A brief review of
      literature along with treatment options is discussed.

PMID- 19843236
TI  - Prophylactic indomethacin in extremely premature infants between 23 and 24 weeks
      gestation.
AB  - BACKGROUND: In extremely premature infants, the presence of a left-to-right shunt
      through a patent ductus arteriosus (PDA) increases the risks of pulmonary
      hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, renal
      failure, and chronic lung disease. Conservative management induces spontaneous
      ductus closure in <20% of extremely premature infants (infants born at <25 weeks
      of gestation). The aim of the present study was to determine the efficacy and
      safety of prophylactic indomethacin (INDO) administration for PDA closure in
      extremely premature infants born between 23 and 24 weeks of gestation. METHODS: A
      historical case-control study of 30 infants born between 23 and 24 weeks of
      gestation was carried out. In the prophylactic INDO group, a 12 h-long, 0.01
      mg/kg per h dose of INDO was administered within 6 h of life. During the
      historical control period, only infants with symptomatic PDA were treated with
      INDO for 1 h. The incidence of symptomatic PDA, mortality and early neonatal
      morbidity was compared between the two groups on Fisher's exact test and Mann
      Whitney rank-sum test. RESULTS: None of the infants in the prophylactic INDO
      group had symptomatic PDA, while 11 of the 15 infants in the control group showed
      symptomatic PDA (P < 0.001). There were no significant differences between the
      mortality rates and the early neonatal morbidities in the two groups.
      CONCLUSIONS: Prophylactic INDO administration to extremely premature infants born
      between 23 and 24 weeks of gestation decreased the incidence of symptomatic PDA
      without increasing the incidence of adverse effects.

PMID- 19843237
TI  - Systemin-dependent salinity tolerance in tomato: evidence of specific convergence
      of abiotic and biotic stress responses.
AB  - Plants have evolved complex mechanisms to perceive environmental cues and develop
      appropriate and coordinated responses to abiotic and biotic stresses.
      Considerable progress has been made towards a better understanding of the
      molecular mechanisms of plant response to a single stress. However, the existence
      of cross-tolerance to different stressors has proved to have great relevance in
      the control and regulation of organismal adaptation. Evidence for the involvement
      of the signal peptide systemin and jasmonic acid in wound-induced salt stress
      adaptation in tomato has been provided. To further unravel the functional link
      between plant responses to salt stress and mechanical damage, transgenic tomato
      (Lycopersicon esculentum Mill.) plants constitutively expressing the prosystemin
      cDNA have been exposed to a moderate salt stress. Prosystemin over-expression
      caused a reduction in stomatal conductance. However, in response to salt stress,
      prosystemin transgenic plants maintained a higher stomatal conductance compared
      with the wild-type control. Leaf concentrations of abscissic acid (ABA) and
      proline were lower in stressed transgenic plants compared with their wild-type
      control, implying that either the former perceived a less stressful environment
      or they adapted more efficiently to it. Consistently, under salt stress,
      transgenic plants produced a higher biomass, indicating that a constitutive
      activation of wound responses is advantageous in saline environment. Comparative
      gene expression profiling of stress-induced genes suggested that the partial
      stomatal closure was not mediated by ABA and/or components of the ABA signal
      transduction pathway. Possible cross-talks between genes involved in wounding and
      osmotic stress adaptation pathways in tomato are discussed.

PMID- 19843238
TI  - Intron polymorphism pattern in AOX1b of wild St John's wort (Hypericum
      perforatum) allows discrimination between individual plants.
AB  - The present paper deals with the analysis of natural polymorphism in a selected
      alternative oxidase (AOX) gene of the medicinal plant, St John's wort. Four
      partial AOX gene sequences were isolated from the genomic DNA of a wild plant of
      Hypericum perforatum L. Three genes belong to the subfamily AOX1 (HpAOX1a, b and
      c) and one to the subfamily AOX2 (HpAOX2). The partial sequence of HpAOX1b showed
      polymerase chain reaction (PCR) fragment size variation as a result of variable
      lengths in two introns. PCR performed by Exon Primed Intron Crossing (EPIC)-PCR
      displayed the same two-band pattern in six plants from a collection. Both
      fragments showed identical sequences for all exons. However, each of the two
      introns showed an insertion/deletion (InDel) in identical positions for all
      plants that counted for the difference in the two fragment sizes. The InDel in
      intron 1 influenced the predictability of a pre-microRNA site. The almost
      identical PCR fragment pattern was characterized by a high variability in the
      sequences. The InDels in both introns were linked to repetitive intron single
      nucleotide polymorphisms (ISNP)s. The polymorphic pattern obtained by InDels and
      ISNPs from both fragments together was appropriate to discriminate between all
      individual plants. We suggest that AOX sequence polymorphism in H. perforatum can
      be used for studies on gene diversity and biodiversity. Further, we conclude that
      AOX sequence polymorphism of individual plants should be considered in biological
      studies on AOX activity to exclude the influence of genetic diversity. The
      identified polymorphic fragments are available to be explored in future
      experiments as a potential source for functional marker development related to
      the characterization of origins/accessions and agronomic traits such as plant
      growth, development and yield stability.

PMID- 19843239
TI  - Effects of iron chlorosis and iron resupply on leaf xylem architecture, water
      relations, gas exchange and stomatal performance of field-grown peach (Prunus
      persica).
AB  - There is increasing evidence suggesting that iron (Fe) deficiency induces not
      only leaf chlorosis and a decline of photosynthesis, but also structural changes
      in leaf morphology, which might affect the functionality of leaves. In this
      study, we investigated the effects of Fe deficiency on the water relations of
      peach (Prunus persica (L.) Batsch.) leaves and the responses of previously
      chlorotic leaves to Fe resupply via the root or the leaf. Iron deficiency induced
      a decline of maximum potential photosystem II (PSII) efficiency (F(V)/F(M)), of
      rates of net photosynthesis and transpiration and of water use efficiency. Iron
      chlorosis was associated with a reduction of leaf xylem vessel size and of leaf
      hydraulic conductance. In the course of the day, water potentials in chlorotic
      leaves remained higher (less negative) than in green leaves. In chlorotic leaves,
      normal stomatal functioning was disturbed, as evidenced by the lack of opening
      upon withdrawal of external CO(2) and stomatal closure after sudden illumination
      of previously darkened leaves. We conclude that the Fe deficiency induced
      limitations of xylem conductivity elicited a water saving strategy, which poses
      an additional challenge to plant growth on high pH, calcareous soils.
      Fertilisation with Fe improved photosynthetic performance but the proper xylem
      structure and water relations of leaves were not fully restored, indicating that
      Fe must be available at the first stages of leaf growth and development.

PMID- 19843240
TI  - Stress-induced changes in glutamate dehydrogenase activity imply its role in
      adaptation to C and N metabolism in lupine embryos.
AB  - The modifying effect of sucrose on glutamate dehydrogenase (GDH) activity and
      isoenzyme pattern was investigated in isolated embryos of lupine (Lupinus luteus
      L.), cultured in vitro in a medium with sucrose (+S) or without sucrose (-S) and
      exposed to cadmium (Cd) and lead (Pb) stress. Sucrose starvation of lupine
      embryos led to a rapid increase in the specific activity of GDH, immunoreactive
      beta-polypeptide and it was accompanied by appearance of new cathodal isoforms of
      enzyme. This suggests that isoenzymes induced in lupine embryos by sucrose
      starvation combine into GDH hexamers with the predominance of beta-GDH subunits
      synthetized under GDH1 gene control. The addition of sucrose to the medium caused
      an opposite effect. Along with upregulation of catabolic activity of GDH by
      sucrose starvation, activity of proteolytic enzymes was also induced. These data
      can point to regulatory mechanism implying a sucrose dependent repression of the
      GDH1 gene according to the mechanism of catabolic repression. Treatment of
      embryos with Cd(2+) or Pb(2+) resulted in ammonium accumulation in the tissues,
      accompanied by an increase in anabolic activity of GDH and activity of anodal
      isoenzymes, in both (+S) and (-S) embryos without new de novo synthesis of alpha
      subunit proteins. Thus, GDH isoenzyme profiles may reflect the physiological
      function of GDH, which appears to be an important link of metabolic adaptation in
      cells, aimed at using carbon sources other than sugar during carbohydrate
      starvation (catabolic activity of GDH) and protecting plant tissues against
      ammonium accumulated because of heavy metal stress (anabolic activity of GDH).

PMID- 19843241
TI  - Temperature responses of substrate carbon conversion efficiencies and growth
      rates of plant tissues.
AB  - Growth rates of plant tissues depend on both the respiration rate and the
      efficiency with which carbon is incorporated into new structural biomass.
      Calorespirometric measurement of respiratory heat and CO2 rates, from which both
      efficiency and growth rate can be calculated, is a well established method for
      determining the effects of rapid temperature changes on the respiratory and
      growth properties of plant tissues. The effect of the alternative
      oxidase/cytochrome oxidase activity ratio on efficiency is calculated from first
      principles. Data on the temperature dependence of the substrate carbon conversion
      efficiency are tabulated. These data show that epsilon is maximum and
      approximately constant through the optimum growth temperature range and decreases
      rapidly as temperatures approach temperature limits to growth. The width of the
      maximum and the slopes of decreasing epsilon at high and low temperatures vary
      greatly with species, cultivars and accessions.

PMID- 19843242
TI  - Variations in constitutive and inducible UV-B tolerance; dissecting photosystem
      II protection in Arabidopsis thaliana accessions.
AB  - The rise in ultraviolet-B (UV-B) (280-315 nm) radiation levels, that is a
      consequence of stratospheric ozone layer depletion, has triggered extensive
      research on the effects of UV-B on plants. Plants raised under natural sunlight
      conditions are generally well protected from the potentially harmful effects of
      UV-B radiation. However, it is mostly unknown to which extent UV protection is
      constitutive and/or induced. In this study, we have analysed the role of
      constitutive and inducible protection responses in avoiding UV-B damage to
      photosystem II of photosynthesis. We have assayed the UV susceptibility of
      photosystem II in 224 Arabidopsis thaliana accessions from across the Northern
      hemisphere, and found a continuum of constitutive UV-protection levels, with some
      accessions being UV sensitive and others UV tolerant. Statistical analysis showed
      only very weak associations between constitutive UV tolerance and the geographic
      origin of accessions. Instead, most of the variance in constitutive UV-B
      protection of photosynthesis is present at the level of local Arabidopsis
      populations originating in the same geographic and climatic area. The variance in
      constitutive UV protection is, however, small compared to the amplitude of
      environmentally induced changes in UV protection. Thus, our data emphasise the
      importance of inducible responses for the protection of photosystem II against UV
      B. Remarkably, the conditions that induce UV-protective responses vary;
      accessions from lower latitudes were found to switch-on UV defences more readily
      than those of higher latitudes. Such altered regulation of induction may comprise
      a suitable adaptation response when levels of a stressor are fluctuating in the
      short term, but predictable over longer periods.

PMID- 19843244
TI  - Melanin precursors prevent premature age-related and noise-induced hearing loss
      in albino mice.
AB  - Strial melanocytes are required for normal development and correct functioning of
      the cochlea. Hearing deficits have been reported in albino individuals from
      different species, although melanin appears to be not essential for normal
      auditory function. We have analyzed the auditory brainstem responses (ABR) of two
      transgenic mice: YRT2, carrying the entire mouse tyrosinase (Tyr) gene expression
      domain and undistinguishable from wild-type pigmented animals; and TyrTH, non
      pigmented but ectopically expressing tyrosine hydroxylase (Th) in melanocytes,
      which generate the precursor metabolite, L-DOPA, but not melanin. We show that
      young albino mice present a higher prevalence of profound sensorineural deafness
      and a poorer recovery of auditory thresholds after noise-exposure than transgenic
      mice. Hearing loss was associated with absence of cochlear melanin or its
      precursor metabolites and latencies of the central auditory pathway were
      unaltered. In summary, albino mice show impaired hearing responses during ageing
      and after noise damage when compared to YRT2 and TyrTH transgenic mice, which do
      not show the albino-associated ABR alterations. These results demonstrate that
      melanin precursors, such as L-DOPA, have a protective role in the mammalian
      cochlea in age-related and noise-induced hearing loss.

PMID- 19843245
TI  - TYRO3-mediated regulation of MITF: a novel target in melanoma?

PMID- 19843243
TI  - Dormancy of metastatic melanoma.
AB  - Metastatic dormancy of melanoma has not received sufficient attention, most
      likely because once detectable, metastasis is almost invariably fatal and,
      understandably, the focus has been on finding ways to prolong life of patients
      with overt recurrences. Nevertheless, analysis of the published clinical and
      experimental data on melanoma indicates that some aspect of melanoma biology
      imitate traits recently associated with dormancy in other solid cancers. Among
      them the ability of some melanomas to disseminate early during primary tumor
      progression and once disseminated, to remain undetected (dormant) for years.
      Comparison of cutaneous and uveal melanoma indicates that, in spite of being of
      the same origin, they differ profoundly in their clinical progression.
      Importantly for this discussion, between 40 and 50% of uveal melanoma remain
      undetected for longer than a decade, while less than 5% of cutaneous melanoma
      show this behavior. Both types of melanoma have activating oncogene mutations
      that provide autonomous pro-proliferative signals, yet the consensus is that
      those are not sufficient for tumor progression. If that is the case, it is
      possible to envision that signals from outside the tumor cell, (microenvironment)
      shape the fate of an individual disseminated cell, regardless of an oncogene
      mutation, to progress or to pause in a state of dormancy. To stimulate further
      debate and inquiry we describe here a few examples of potential signals that
      might modify the fate of disseminated cell and provide brief description of the
      current knowledge on dormancy in other cancers. Our hope is to convince the
      reader that disseminated melanoma cells do enter periods of prolonged dormancy
      and that finding ways to induce it, or to prolong it, might mean an extension of
      symptoms-free life for melanoma patients. Ultimately, understanding the biology
      of dormancy and the mechanisms of dormant cell survival, might allow for their
      specific targeting and elimination.

PMID- 19843248
TI  - A systems approach to plant bioprocess optimization.
AB  - A dynamic model for plant cell metabolism was used as a basis for a rational
      analysis of plant production potential in in vitro cultures. The model was
      calibrated with data from 3-L bioreactor cultures. A dynamic sensitivity analysis
      framework was developed to analyse the response curves of secondary metabolite
      production to metabolic and medium perturbations. Simulation results suggest that
      a straightforward engineering of cell metabolism or medium composition might only
      have a limited effect on productivity. To circumvent the problem of the dynamic
      allocation of resources between growth and production pathways, the sensitivity
      analysis framework was used to assess the effect of stabilizing intracellular
      nutrient concentrations. Simulations showed that a stabilization of intracellular
      glucose and nitrogen reserves could lead to a 116% increase in the specific
      production of secondary metabolites compared with standard culture protocol. This
      culture strategy was implemented experimentally using a perfusion bioreactor. To
      stabilize intracellular concentrations, adaptive medium feeding was performed
      using model mass balances and estimations. This allowed for a completely
      automated culture, with controlled conditions and pre-defined decision making
      algorithm. The proposed culture strategy leads to a 73% increase in specific
      production and a 129% increase in total production, as compared with a standard
      batch culture protocol. The sensitivity analysis on a mathematical model of plant
      metabolism thus allowed producing new insights on the links between intracellular
      nutritional management and cell productivity. The experimental implementation was
      also a significant improvement on current plant bioprocess strategies.

PMID- 19843246
TI  - AKT2 is a downstream target of metabotropic glutamate receptor 1 (Grm1).
AB  - We reported earlier on the oncogenic properties of Grm1 by demonstrating that
      stable Grm1-mouse-melanocytic clones proliferate in the absence of growth
      supplement and anchorage in vitro. In addition, these clones also exhibit
      aggressive tumorigenic phenotypes in vivo with short latency in tumor formation
      in both immunodeficient and syngeneic mice. We also detected strong activation of
      AKT in allograft tumors specifically AKT2 as the predominant isoform involved. In
      parallel, we assessed several human melanoma biopsy samples and found again that
      AKT2 was the predominantly activated AKT in these human melanoma biopsies. In
      cultured stable Grm1-mouse-melanocytic clones, as well as an metabotropic
      glutamate receptor 1 (Grm1) expressing human melanoma cell line, C8161,
      stimulation of Grm1 by its agonist led to the activation of AKT, while
      preincubation with Grm1-antagonist abolished Grm1-agonist-induced AKT activation.
      In addition, a reduction in tumor volume of Grm1-mouse-melanocytic-allografts was
      detected in the presence of small interfering AKT2 RNA (siAKT2). Taken together,
      these results showed that, in addition to the MAPK pathway previously reported
      being a downstream target of stimulated Grm1, AKT2 is another downstream target
      in Grm1 mediated melanocyte transformation.

PMID- 19843249
TI  - Influence of elastin-like peptide fusions on the quantity and quality of a
      tobacco-derived human immunodeficiency virus-neutralizing antibody.
AB  - The use of vaginal microbicides containing human immunodeficiency virus (HIV)
      neutralizing antibodies (nAbs) is a promising strategy to prevent HIV-1
      infection. Although antibodies are predominantly manufactured using mammalian
      cells, elastin-like peptide (ELP) fusion technology improves the stability of
      recombinant, plant-produced proteins and facilitates their purification, making
      plants an alternative platform for antibody production. We generated transgenic
      tobacco plants accumulating four different formats of the anti-HIV-1 antibody
      2G12 in the endoplasmic reticulum (ER), i.e. with ELP on either the light or
      heavy chain, on both, or on neither. Detailed analysis of affinity-purified
      antibodies by surface plasmon resonance spectroscopy showed that the kinetic
      binding parameters of all formats were identical to 2G12 lacking ELP produced in
      Chinese hamster ovary (CHO) cells. Importantly, protein purification from seeds
      by inverse transition cycling (ITC) did not affect the binding kinetics. Analysis
      of heavy chain N-glycans from leaf-derived antibodies showed that retrieval to
      the ER was efficient for all formats. In seeds, however, N-glycans on the naked
      antibody were extensively trimmed compared with those on the ELP fusion formats,
      and were localized to a different subcellular compartment. The in vitro HIV
      neutralization properties of the tobacco-derived 2G12 were equivalent to or
      better than those of the CHO counterpart.

PMID- 19843250
TI  - Tuber-specific cphA expression to enhance cyanophycin production in potatoes.
AB  - The production of biodegradable polymers that can be used to substitute
      petrochemical compounds in commercial products in transgenic plants is an
      important challenge for plant biotechnology. Nevertheless, it is often
      accompanied by reduced plant fitness. To decrease the phenotypic abnormalities of
      the sprout and to increase polymer production, we restricted cyanophycin
      accumulation to the potato tubers by using the cyanophycin synthetase gene
      (cphA(Te)) from Thermosynechococcus elongatus BP-1, which is under the control of
      the tuber-specific class 1 promoter (B33). Tuber-specific cytosolic (pB33
      cphA(Te)) as well as tuber-specific plastidic (pB33-PsbY-cphA(Te)) expression
      resulted in significant polymer accumulation solely in the tubers. In plants
      transformed with pB33-cphA(Te), both cyanophycin synthetase and cyanophycin were
      detected in the cytoplasm leading to an increase up to 2.3% cyanophycin of dry
      weight and resulting in small and deformed tubers. In B33-PsbY-cphA(Te) tubers,
      cyanophycin synthetase and cyanophycin were exclusively found in amyloplasts
      leading to a cyanophycin accumulation up to 7.5% of dry weight. These tubers were
      normal in size, some clones showed reduced tuber yield and sometimes exhibited
      brown sunken staining starting at tubers navel. During a storage period over of
      32 weeks of one selected clone, the cyanophycin content was stable in B33-PsbY
      cphA(Te) tubers but the stress symptoms increased. However, all tubers were able
      to germinate. Nitrogen fertilization in the greenhouse led not to an increased
      cyanophycin yield, slightly reduced protein content, decreased starch content,
      and changes in the amounts of bound and free arginine and aspartate, as compared
      with control tubers were observed.

PMID- 19843251
TI  - Molecular cloning and characterization of a KCS gene from Cardamine graeca and
      its heterologous expression in Brassica oilseeds to engineer high nervonic acid
      oils for potential medical and industrial use.
AB  - Nervonic acid 24:1 Delta15 (cis-tetracos-15-enoic acid) is a very long-chain
      monounsaturated fatty acid and exists in nature as an elongation product of oleic
      acid. There is an increasing interest in production of high nervonic acid oils
      for pharmaceutical, nutraceutical and industrial applications. Using a polymerase
      chain reaction approach, we have isolated a gene from Cardamine graeca L., which
      encodes a 3-ketoacyl-CoA synthase (KCS), the first component of the elongation
      complex involved in synthesis of nervonic acid. Expression of the Cardamine KCS
      in yeast resulted in biosynthesis of nervonic acid, which is not normally present
      in yeast cells. We transformed Arabidopsis and Brassica carinata with the
      Cardamine KCS under the control of the seed-specific promoter, napin. The T(3)
      generations of transgenic Arabidopsis and B. carinata plants expressing the
      Cardamine KCS showed that seed-specific expression resulted in relatively large
      comparative increases in nervonic acid proportions in Arabidopsis seed oil, and
      15-fold increase in nervonic acid proportions in B. carinata seed oil. The
      highest nervonic acid level in transgenic B. carinata lines reached 44%, with
      only 6% of residual erucic acid. In contrast, similar transgenic expression of
      the Cardamine KCS in high erucic B. napus resulted in 30% nervonic acid but with
      20% residual erucic acid. Experiments using the Lunaria KCS gene gave results
      similar to the latter. In both cases, the erucic acid content is too high for
      human or animal consumption. Thus, the Cardamine KCS: B. carinata high
      nervonic/highly reduced erucic transgenic seed oils will be the most suitable for
      testing in pharmaceutical/nutraceutical applications to improve human and animal
      health.

PMID- 19843252
TI  - A leaf-based assay using interchangeable design principles to rapidly assemble
      multistep recombinant pathways.
AB  - The assembly of multistep recombinant pathways in stably transformed plants is a
      cornerstone of crops producing new products yet can be a laborious and time
      consuming process. Any heterologous expression platform capable of providing a
      rapid estimation of the functional assembly of an entire pathway would guide the
      design of such transgenic traits. In this study, we use a Nicotiana benthamiana
      transient leaf expression system to simultaneously express five genes, from five
      independent T(DNA) binary vectors, to assemble a complete recombinant pathway in
      five days. In this study, we demonstrate the production of long-chain
      polyunsaturated fatty acids (LC-PUFA) requiring five transgene-encoded reactions
      to convert endogenous fatty acids to LC-PUFA. The addition of a triacylglycerol
      assembly enzyme, Arabidopsis thaliana diacylglyceride-O-acyltransferase, and
      fractionation of the total lipid profile demonstrated that leaf oils contained
      37% newly synthesised LC-PUFA, including 7% arachidonic acid (AA), 6%
      eicosopentaenoic acid and 3% docosahexaenoic acid. The calculation of enzymatic
      conversion efficiencies at each step of LC-PUFA synthesis suggests that this
      transient assembly of a complicated multistep pathway is highly efficient. Unlike
      experiments using stably transformed plants our assembly of an intricate pathway
      maintained full gene-for-gene interchangeability and required a fraction of the
      time and glasshouse space. Furthermore, an exogenous LC-PUFA fatty acid
      substrate, AA, was fed and metabolised by a transiently expressed Delta17
      desaturase enzyme, and provided results similar to those obtained in yeast
      feeding experiments. Although the assay was ideal for LC-PUFA pathways, this
      assay format may become a powerful tool for the characterisation and step-wise
      improvement of other recombinant pathways and multigenic traits.

PMID- 19843253
TI  - Analysis of the salt-stress response at cell-type resolution.
AB  - Albert Einstein said that one should make everything as simple as possible, but
      not simpler. Likewise, biologists have often relied upon simplifying assumptions
      to study the fundamental properties of biological systems. To understand how
      complex multicellular plants respond to stresses such as high salinity, organ or
      organism-scale experiments have often been the standard and have led to important
      discoveries. However, recently, through the use of cell-type-specific analyses,
      it has become clear that most salt-stress regulation occurs at the scale of the
      cell or tissue type. Salt stress has been revealed to cause complex changes in
      growth, development and physiology that are dynamically regulated in both space
      and time. Thus, the next most important discoveries regarding how plants
      perceive, respond and adapt to this environmental stimulus will require
      approaches that enable high-resolution spatial and temporal observations to be
      made. In this review, we highlight studies taking both a genomic and sub-genomic
      approach to understand the salt response at high spatial resolution. These
      present and future studies will help lead to a more sophisticated understanding
      of the root as a complex system, which integrates information from different cell
      layers to generate synchronized changes necessary for the survival of the plant.

PMID- 19843254
TI  - Porteresia coarctata (Roxb.) Tateoka, a wild rice: a potential model for studying
      salt-stress biology in rice.
AB  - Porteresia coarctata (Syn = Oryza coarctata) is a tetraploid wild rice growing
      abundantly in the coastal region of India and some other Asian countries. The
      salt tolerance property of this mangrove associate has been dealt with by a
      number of workers earlier. The distinct morphology and leaf architecture enabling
      the plant to exclude salt is a characteristic feature of Porteresia in comparison
      with Oryza sp. A number of genes have been isolated and characterized from
      Porteresia that are related to the salt-tolerance property of the plant. Evidence
      have accumulated that some pathways critical to salt tolerance are in operation
      in Porteresia of which the inositol metabolic pathway has been recently
      elaborated. Some of the enzymes of Porteresia have been shown to function as salt
      tolerant under in vitro studies giving a clue that this wild halophytic rice may
      have evolved genes and proteins capable of functioning under a salt environment.
      Bioprospecting of such genes and proteins coupled with genomic and proteomic
      approaches remain an exciting area of research in evaluating this plant as a
      model for salt tolerance for the rice plant.

PMID- 19843255
TI  - Extracellular superoxide production, viability and redox poise in response to
      desiccation in recalcitrant Castanea sativa seeds.
AB  - Reactive oxygen species (ROS) are implicated in seed death following dehydration
      in desiccation-intolerant 'recalcitrant' seeds. However, it is unknown if and how
      ROS are produced in the apoplast and if they play a role in stress signalling
      during desiccation. We studied intracellular damage and extracellular superoxide
      (O(2)(.-)) production upon desiccation in Castanea sativa seeds, mechanisms of
      O(2)(.-) production and the effect of exogenously supplied ROS. A transient
      increase in extracellular O(2)(.-) production by the embryonic axes preceded
      significant desiccation-induced viability loss. Thereafter, progressively more
      oxidizing intracellular conditions, as indicated by a significant shift in
      glutathione half-cell reduction potential, accompanied cell and axis death,
      coinciding with the disruption of nuclear membranes. Most hydrogen peroxide
      (H(2)O(2))-dependent O(2)(.-) production was found in a cell wall fraction that
      contained extracellular peroxidases (ECPOX) with molecular masses of
      approximately 50 kDa. Cinnamic acid was identified as a potential reductant
      required for ECPOX-mediated O(2)(.-) production. H(2)O(2), applied exogenously to
      mimic the transient ROS burst at the onset of desiccation, counteracted viability
      loss of sub-lethally desiccation-stressed seeds and of excised embryonic axes
      grown in tissue culture. Hence, extracellular ROS produced by embryonic axes
      appear to be important signalling components involved in wound response,
      regeneration and growth.

PMID- 19843256
TI  - Drought, ozone, ABA and ethylene: new insights from cell to plant to community.
AB  - Recent reports show ethylene-dependent reductions in stomatal sensitivity to
      abscisic acid (ABA) under ozone stress. These changes reduce stomatal control of
      plant water loss in drying soil. Here we review evidence that ABA and ethylene,
      and interactions between these two stress-induced hormones, control many of the
      responses of intact plants to drought and ozone stress, with emphasis on effects
      on stomata and shoot growth. We draw attention to convergent signalling and
      response pathways induced by ozone and drought that can increase production of
      hydrogen peroxide (H(2)O(2)) and nitric oxide (NO). Stomatal responses to a wider
      range of stresses and developmental cues may also be controlled via the same sets
      of signalling pathways. Other hormones, or effectors such as xylem/apoplastic pH
      or changes in plant water status, also play a role in signalling within and
      between organs. We discuss the implications, for crops, natural ecosystems and
      water catchment processes, of ethylene's antagonism of the stomatal response to
      ABA, against a back-drop of predictions for reduced precipitation and increasing
      ozone pollution, as part of global climate change and increasing urbanization and
      industrial development.

PMID- 19843257
TI  - Salt sensitivity in chickpea.
AB  - The growth of chickpea (Cicer arietinum L.) is very sensitive to salinity, with
      the most susceptible genotypes dying in just 25 mm NaCl and resistant genotypes
      unlikely to survive 100 mm NaCl in hydroponics; germination is more tolerant with
      some genotypes tolerating 320 mm NaCl. When growing in a saline medium, Cl(-),
      which is secreted from glandular hairs on leaves, stems and pods, is present in
      higher concentrations in shoots than Na(+). Salinity reduces the amount of water
      extractable from soil by a chickpea crop and induces osmotic adjustment, which is
      greater in nodules than in leaves or roots. Chickpea rhizobia show a higher 'free
      living' salt resistance than chickpea plants, and salinity can cause large
      reductions in nodulation, nodule size and N(2)-fixation capacity. Recent
      screenings of diverse germplasm suggest significant variation of seed yield under
      saline conditions. Both dominance and additive gene effects have been identified
      in the effects of salinity on chickpea and there appears to be sufficient genetic
      variation to enable improvement in yield under saline conditions via breeding.
      Selections are required across the entire life cycle with a range of rhizobial
      strains under salt-affected, preferably field, conditions.

PMID- 19843258
TI  - Suppression of sorghum axillary bud outgrowth by shade, phyB and defoliation
      signalling pathways.
AB  - In recent years, several genetic components of vegetative axillary bud
      development have been defined in both monocots and eudicots, but our
      understanding of environmental inputs on branching remains limited. Recent work
      in sorghum (Sorghum bicolor) has revealed a role for phytochrome B (phyB) in the
      control of axillary bud outgrowth through the regulation of Teosinte Branched1
      (TB1) gene. In maize (Zea mays), TB1 is a dosage-dependent inhibitor of axillary
      meristem progression, and the expression level of TB1 is a sensitive measure of
      axillary branch development. To further explore the mechanistic basis of
      branching, the expression of branching and cell cycle-related genes were examined
      in phyB-1 and wild-type sorghum axillary buds following treatment with low-red :
      far-red light and defoliation. Although defoliation inhibited bud outgrowth, it
      did not influence the expression of sorghum TB1 (SbTB1), whereas changes in
      SbMAX2 expression, a homolog of the Arabidopsis (Arabidopsis thaliana) branching
      inhibitor MAX2, were associated with the regulation of bud outgrowth by both
      light and defoliation. The expression of several cell cycle-related genes was
      also decreased dramatically in buds repressed by defoliation, but not by phyB
      deficiency. The data suggest that there are at least two distinct molecular
      pathways that respond to light and endogenous signals to regulate axillary bud
      outgrowth.

PMID- 19843259
TI  - Weather and climate controls over the seasonal carbon isotope dynamics of sugars
      from subalpine forest trees.
AB  - We examined the environmental variables that influence the delta(13)C value of
      needle and phloem sugars in trees in a subalpine forest. We collected sugars from
      Pinus contorta, Picea engelmannii and Abies lasiocarpa from 2006 to 2008. Phloem
      and needle sugars were enriched in (13)C during the autumn, winter and early
      spring, but depleted during the growing season. We hypothesized that the late
      winter and early-spring (13)C enrichment was due to the mobilization of carbon
      assimilated the previous autumn; however, needle starch concentrations were
      completely exhausted by autumn, and we observed evidence of new starch production
      during episodic warm weather events during the winter and early-spring. Instead,
      we found that (13)C enrichment was best explained by the occurrence of cold night
      time temperatures. We also observed seasonal decoupling in the (13)C/(12)C ratios
      of needle and phloem sugars. We hypothesized that this was due to seasonally
      changing source-sink patterns, which drove carbon translocation from the needles
      towards the roots early in the season, before bud break, but from the roots
      towards the needles later in the season, after bud break. Overall, our results
      demonstrate that the (13)C/(12)C ratio of recently-assimilated sugars can provide
      a sensitive record of the short-term coupling between climate and tree
      physiology.

PMID- 19843260
TI  - School violence and the culture of honor.
AB  - We investigated the hypothesis that a sociocultural variable known as the culture
      of honor would be uniquely predictive of school-violence indicators. Controlling
      for demographic characteristics associated in previous studies with violent crime
      among adults, we found that high-school students in culture-of-honor states were
      significantly more likely than high-school students in non-culture-of-honor
      states to report having brought a weapon to school in the past month. Using data
      aggregated over a 20-year period, we also found that culture-of-honor states had
      more than twice as many school shootings per capita as non-culture-of-honor
      states. The data revealed important differences between school violence and
      general patterns of homicide and are consistent with the view that many acts of
      school violence reflect retaliatory aggression springing from intensely
      experienced social-identity threats.

PMID- 19843261
TI  - Decisions under distress: stress profiles influence anchoring and adjustment.
AB  - People frequently make decisions under stress. Understanding how stress affects
      decision making is complicated by the fact that not all stress responses are
      created equal. Challenge states, for example, occur when individuals appraise a
      stressful situation as demanding, but believe they have the personal resources to
      cope, and are characterized by efficient cardiovascular reactivity and approach
      motivation. Threat states, in contrast, occur when situational demands are
      perceived to outweigh resources and are characterized by less efficient
      cardiovascular reactivity and withdrawal motivation. We randomly assigned
      participants to social-feedback conditions (i.e., positive or negative feedback)
      designed to engender challenge or threat, or a no-stress condition. Participants
      then completed an anchoring-and-adjustment questionnaire. Those assigned to the
      challenge condition adjusted more from self-generated anchors than those assigned
      to the threat condition. Cardiovascular responses mediated the relationship
      between condition and adjustment. This study demonstrates the importance of
      considering profiles of cardiovascular reactivity when examining the influence of
      stress on decision making.

PMID- 19843262
TI  - Selective attention and perceptual load in autism spectrum disorder.
AB  - It has been suggested that the locus of selective attention (early vs. late in
      processing) is dependent on the perceptual load of the task. When perceptual load
      is low, irrelevant distractors are processed (late selection), whereas when
      perceptual load is high, distractor interference disappears (early selection).
      Attentional abnormalities have long been reported within autism spectrum disorder
      (ASD), and this study is the first to examine the effect of perceptual load on
      selective attention in this population. Fourteen adults with ASD and 23 adults
      without ASD performed a selective attention task with varying perceptual loads.
      Compared with the non-ASD group, the ASD group required higher levels of
      perceptual load to successfully ignore irrelevant distractors; moreover, the ASD
      group did not show any general reduction in performance speed or accuracy. These
      results suggest enhanced perceptual capacity in the ASD group and are consistent
      with previous observations regarding superior visual search abilities among
      individuals with ASD.

PMID- 19843263
TI  - Order in choice: effects of serial position on preferences.
AB  - When several choice options are sampled one at a time in a sequence and a single
      choice of the best option is made at the end of the sequence, which location in
      the sequence is chosen most often? We report a large-scale experiment that
      assessed tasting preferences in choice sets of two, three, four, or five wines.
      We found a large primacy effect-the first wine had a large advantage in the end
      of-sequence choice. We also found that participants who were knowledgeable about
      wines showed a recency effect in the longer sequences. We conclude with a process
      model that explains our findings.

PMID- 19843264
TI  - Single muscle fiber properties in aging and disuse.
AB  - Since the middle of the 1980s, it was understood that myosin, the motor of
      contraction, can be expressed in several isoforms. The isoforms of the myosin
      heavy-chain (MHC) portion of the molecule were found to be mostly responsible for
      the diversity in the contractile and energetic properties of muscle fibers. In
      humans, three MHC isoforms are expressed in limb muscles (MHC-1, MHC-2A and MHC
      2X) and they generate three pure fiber types (types 1, 2A and 2X) and two hybrid
      types (types 1-2A and -2AX). Type 1, 2A and 2X fibers widely differ with respect
      to most of their contractile and energetic properties, and a change in their
      relative distribution within muscles is known to modulate their functional
      properties in vivo through a "qualitative" mechanism. On the basis of the MHC
      regulation of muscle fibers properties, it is expected that a given fiber type
      develops the same force and shortens at the same speed regardless of the
      physiologic and pathologic conditions under which the muscle works. Surprisingly,
      several evidences have been accumulating to show that in aging and disuse, the
      properties of a muscle fiber type can change with no change in its myosin isoform
      content. This short review considers the latter phenomenon and the possible
      underlying mechanisms.

PMID- 19843265
TI  - Digit ratio (2D:4D) predicts sporting success among female fencers independent
      from physical, experience, and personality factors.
AB  - Research particularly focusing on male athletes and popular sports (running and
      soccer) suggests associations of lower (masculinized) second-to-fourth digit
      ratio (2D:4D), a putative marker of prenatal androgen action, with better sports
      performance. Studies focusing on women, non-mainstream sports, or controlling for
      covariates relevant for sporting success are still sparse. This study examined
      associations between 2D:4D and performance of both male and female athletes
      active in fencing (a non-mainstream sport dominated by male participants), while
      controlling for covariates. National fencing rankings and 2D:4D of 58 male and 41
      female Austrian tournament fencers (mean age 24 years) were correlated. Among
      female, but not male, fencers, lower 2D:4D was related to better national fencing
      rankings. 2D:4D still accounted for incremental variance (12%) in fencing
      success, when the effects of salient performance factors (age, body mass index,
      years of fencing, training intensity, and the personality variables achievement,
      control, harm avoidance, and social potency) were controlled for (totaling 35%
      attributable variance). Athletes active in the most aggressive form (the sabre)
      had lower 2D:4D than those active in the other forms (epee and foil fencing).
      Sporting success in adult life might be partly prenatally programmed via long
      lasting extragenital effects of testosterone.

PMID- 19843266
TI  - Use of performance- and image-enhancing substances among recreational athletes: a
      quantitative analysis of inquiries submitted to the Danish anti-doping
      authorities.
AB  - The use of performance- and image-enhancing drugs/substances (PIED) outside elite
      sports appears to be increasing, although the current knowledge of the nature of
      PIED use among recreational athletes is scarce. The present study analyzed
      enquiries that were submitted to the Danish Anti Doping Agency (ADD) over an 18
      month period, to gain knowledge of PIED use among individuals who exercise
      recreationally in Denmark. One thousand three hundred ninety eight queries were
      examined with respect to the age and gender of the enquirer, affiliation to sport
      or exercise and substance in question. The key findings were that the ADD
      information service is generally used by males in their mid-20s who exercise in
      gyms and are not engaged in competitive sports. Approximately 15% of the
      enquirers were users of anabolic androgenic steroids (AAS) or other substances
      banned within elite sports by the World Anti Doping Agency, and an additional 15%
      considered using such substances. The present results suggest that there is a
      pronounced interest in the use of AAS and other PIEDs among Danish gym members.

PMID- 19843267
TI  - Beyond 'doctor and patient': developments in the study of healthcare
      interactions.
AB  - Three decades of conversation analytic investigations of medical interaction have
      produced a rich collection of findings of sociological interest, from a diverse
      array of encounters. This paper briefly outlines the development of this field to
      provide a context for the special issue. The paper discusses how studies of
      doctor-patient interaction have revealed the ways in which participants organise
      the medical visit to accomplish tasks such as diagnosing and recommending
      treatment for illness, and how doctors and patients address various interactional
      issues and dilemmas that arise as they undertake these tasks. It then highlights
      a growing number of CA studies that explore medical settings and activities
      beyond the doctor-patient encounter. In doing so, it charts the distinctive
      interactional practices that emerge, for example, where participants are engaging
      in hands-on treatment, medical practitioners are interacting with one another, or
      various technologies are employed during the encounter. Finally, papers in this
      special issue are introduced and shown to build upon this latter tradition. The
      papers address distinctive practical problems and institutional dilemmas that
      arise in healthcare encounters and medical settings beyond dyadic doctor-patient
      interaction, with a focus on the participants' orientations to policy, their
      distinctive modes of participation, and the use of technology.

PMID- 19843268
TI  - Dialling for donations: practices and actions in the telephone solicitation of
      human tissues.
AB  - Altruistic actions such as the donation of public goods have long been the
      subject of social scientific debate. While scholars have recognised the
      importance of analysing the solicitation of donated goods such as human organs
      and tissues, to date none has examined actual interaction for this fateful event
      as it unfolds in real time. In this paper, we use data from 186 audio-recorded
      telephone interactions between donation centre personnel and family members of
      the recently deceased along with in-depth interviews and observations conducted
      in the call centre, to examine this particular donation solicitation interaction.
      Using conversation analysis, we demonstrate the step-by-step sequencing of the
      interaction that begins with the ringing phone generated by the call centre
      personnel which eventually leads to the formulation of the reason for the call,
      the tacit donation solicitation. Our close analysis of the sequential
      organisation of this interaction shows how solicitation is done cautiously,
      incrementally, and tacitly rather than overtly, reflecting its status as a
      dispreferred action. This analysis suggests that configurations in the wording of
      solicitations may operate interactionally but inadvertently to discourage the act
      of donation that call centre personnel are attempting to elicit.

PMID- 19843269
TI  - Managing medical advice seeking in calls to Child Health Line.
AB  - Child Health Line is a 24-hour Australian helpline that offers information and
      support for parents and families on child development and parenting. The helpline
      guidelines suggest that nurses should not offer medical advice; they do, however,
      regularly receive calls seeking such advice. This paper examines how the service
      guidelines are talked into being through the nurses' management of callers'
      requests for medical advice and information, and shows how nurses orient to the
      boundaries of their professional role and institutionally regulated authority.
      Three ways in which the child health nurses manage medical advice and information
      seeking are discussed: using membership as a nurse to establish boundaries of
      expertise, privileging parental authority regarding decision making about seeking
      treatment for their child, and respecifying a 'medical' problem as a child
      development issue. The paper contributes to research on medical authority, and
      nurse authority in particular, by demonstrating the impact of institutional roles
      and guidelines on displays of knowledge and expertise. More generally, it
      contributes to an understanding of the interactional enactment and consequences
      of service guidelines for telehealth practice, with implications for training,
      policy and service delivery.

PMID- 19843270
TI  - Practitioners' accounts for treatment actions and recommendations in
      physiotherapy: when do they occur, how are they structured, what do they do?
AB  - This paper examines healthcare communication between physiotherapists and
      patients during treatment sessions, using the perspectives and methods of
      conversation analysis. In particular, it examines communication about reasons and
      rationale for treatment actions by analysing physiotherapists' accounts
      (explanations) for these actions during treatment sessions. Circumstances in
      which accounts arise are identified, structural aspects described and their
      functions demonstrated. These accounts can be persuasive, can foster mutuality,
      minimise resistance and provide education. They contribute to sensitive handling
      of patients' physical failures and of removing clothing. Questions arising, but
      as yet unanswered, include whether clinicians' accounts impact on patients'
      perceptions and their long-term outcomes. Analysis sheds some light on why
      observers have found accounts are uncommon in actual consultations. It thereby
      contributes to sociological understandings about why certain matters are and are
      not communicated during healthcare encounters, demonstrating the significance of
      practical and interactional constraints. The findings also provide clinically
      relevant information about when and how accounts can be provided, and what
      accounting can achieve in terms of both local procedures and the overall
      character of the consultation and relationship.

PMID- 19843271
TI  - 'I've put weight on cos I've bin inactive, cos I've 'ad me knee done': moral work
      in the obesity clinic.
AB  - As governments and healthcare systems grow increasingly concerned with the
      current obesity 'epidemic', sociological interest in the condition has also
      increased. Despite the emergence of work discussing obesity as a social
      phenomenon, the sociological dimensions of medical weight-loss treatments for
      obesity remain underexplored. This paper reports on a conversation analytic (CA)
      study and describes how moral issues surrounding weight and patienthood become
      visible when doctors and patients discuss obesity. Consultations in two UK
      National Health Service clinics were video-recorded and analysed to identify
      recurring patterns of interaction. This paper describes how patients answer
      opening questions: questions which begin the consultation, enabling patients to
      report their medical status. Analysis reveals that when producing their answers,
      patients typically imply either 'success' or 'lack of success' in their weight
      loss progress. Whilst doing so, they construct their personal agency in different
      ways, crediting themselves for implied successes and resisting responsibility for
      lack of success. Through interaction the doctor and patient collaboratively
      construct obesity as a moral issue. The moral obligations invoked share
      similarities with certain perceived normative dynamics surrounding obesity and
      the responsibilities of patienthood. These findings have relevance to healthcare
      practice and add to sociological understanding of the modern obesity 'crisis'.

PMID- 19843272
TI  - Embedding instruction in practice: contingency and collaboration during surgical
      training.
AB  - In this paper we address the ways in which surgeons, in collaboration with other
      members of the surgical team, create occasions for demonstration and instruction
      within the highly complex and demanding tasks of a surgical operation. Drawing on
      video recordings of surgical operations, augmented by field studies, we examine
      how particular phenomena and procedures are made accessible and intelligible to
      trainees and the ways in which brief episodes of insight and instruction enable
      complex procedures to be followed and understood. We consider the ways in which
      demonstration and instruction are achieved, whilst preserving the integrity of
      medical practice, and explore how trainees are provided with the opportunity to
      witness, and learn from, the contingent deployment of formal procedures in
      particular cases. We conclude by considering our observations in the light of
      recent discussions of practice and situated learning in healthcare training.

PMID- 19843273
TI  - Creating history: documents and patient participation in nurse-patient
      interviews.
AB  - Strongly worded directives regarding the need for increased patient participation
      during nursing interaction with patients have recently appeared in a range of
      'best-practice' documents. This paper focuses on one area of nurse-patient
      communication, the hospital admission interview, which has been put forward as an
      ideal arena for increased patient participation. It uses data from a total of 27
      admission interviews, extensive periods of participant observation and analysis
      of nursing records to examine how hospital admission interviews are performed by
      nurses and patients. Analysis shows that topics discussed during admission
      closely follow the layout of the admission document which nurses complete during
      the interview. Whilst it is tempting to describe the admission document as a
      'super technological power' in influencing the interaction and restricting
      patient participation, this analysis attempts a more rounded reading of the data.
      Findings demonstrate that, whilst opportunities for patient participation were
      rare, admission interviews are complex interactional episodes that often belie
      simplistic or prescriptive guidance regarding interaction between nurses and
      patients. In particular, issue is taken with the lack of contextual and
      conceptual clarity with which best-practice guidelines are written.

PMID- 19843274
TI  - Listening to what is said--transcribing what is heard: the impact of speech
      recognition technology (SRT) on the practice of medical transcription (MT).
AB  - Medical records have become central to nearly all aspects of healthcare. However,
      little research exists on their creation. Using data from an ongoing ethnographic
      study of healthcare documentation production, this paper examines the process of
      medical record creation through the use of speech recognition technology (SRT)
      and subsequent editing by medical transcriptionists (MTs). Informed by
      ethnomethodology (EM) and conversation analysis (CA), the results demonstrate the
      professional knowledge involved in the work of medical transcription, which
      includes a combination of skilled worksite practices and an orientation toward
      the social order properties of recorded dictation. Furthermore, we examine how
      the advantages and limitations of SRTs can impact the work of transcription. We
      conclude with strategic recommendations for using SRTs to support medical records
      production and recommend against total automation.

PMID- 19843277
TI  - HLA-B*0777 allele differs from B*0707 by a single residue in the antigen binding
      groove.
AB  - Human leukocyte antigen (HLA) class I sequence-based typing (SBT) for
      hematopoietic unrelated donor searching in a Romanian Caucasian patient showed
      the presence of a novel HLA-B allele defined as B*0777. HLA-B*0777 has two
      nucleotides changes at the same codon from B*0707, resulting an amino acid
      replacement 99Y > 99S.

PMID- 19843278
TI  - Identification of a novel HLA-Cw*08 variant allele, Cw*0824.
AB  - A novel HLA-C allele, Cw*0824, which was identified from an individual of the Han
      Chinese, differs from Cw*080101 at codon 222 (GAG > AAG ) in exon 4, which
      results in an amino acid change Glu222Lys.

PMID- 19843279
TI  - Successful implementation of a national HLA-B*5701 genetic testing service in
      Canada.
AB  - Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) that is used in
      combination antiretroviral therapy in HIV-infected patients. It is currently
      recommended as a preferred or an alternative NRTI in antiretroviral-naive
      patients. The major toxicity of abacavir is a hypersensitivity reaction (HSR),
      which occurs in approximately 5% of treated patients. There is a strong
      association between the human leukocyte antigen (HLA)-B*5701 allele and abacavir
      HSR, which has allowed for rapid acceptance of genetic screening for HLA-B*5701
      in clinical use. Canadian clinicians working in hospital centers with HLA typing
      capacity opted to launch a pilot project in 2006 to offer the screening test as
      standard of care to HIV-infected patients. Currently, more than 11,000 HLA-B*5701
      tests have been performed, among which 6.3% are positive. Continued efforts have
      been made to ensure that testing is available to all HIV-infected patients to
      widen the patients' therapeutic options. HLA-B*5701 screening shows clinical use
      and preliminary data suggest cost-effectiveness.

PMID- 19843280
TI  - Roles of an unconventional protein kinase and myosin II in amoeba osmotic shock
      responses.
AB  - The contractile vacuole (CV) is a dynamic organelle that enables Dictyostelium
      amoeba and other protist to maintain osmotic homeostasis by expelling excess
      water. In the present study, we have uncovered a mechanism that coordinates the
      mechanics of the CV with myosin II, regulated by VwkA, an unconventional protein
      kinase that is conserved in an array of protozoa. Green fluorescent protein (GFP)
      VwkA fusion proteins localize persistently to the CV during both filling and
      expulsion phases of water. In vwkA null cells, the established CV marker dajumin
      still localizes to the CV, but these structures are large, spherical and severely
      impaired for discharge. Furthermore, myosin II cortical localization and assembly
      are abnormal in vwkA null cells. Parallel analysis of wild-type cells treated
      with myosin II inhibitors or of myosin II null cells also results in enlarged CVs
      with impaired dynamics. We suggest that the myosin II cortical cytoskeleton,
      regulated by VwkA, serves a critical conserved role in the periodic contractions
      of the CV, as part of the osmotic protective mechanism of protozoa.

PMID- 19843281
TI  - Subcellular distribution of tail-anchored proteins in Arabidopsis.
AB  - Tail-anchored (TA) proteins function in key cellular processes in eukaryotic
      cells, such as vesicle trafficking, protein translocation and regulation of
      transcription. They anchor to internal cell membranes by a C-terminal
      transmembrane domain, which also serves as a targeting sequence. Targeting occurs
      post-translationally, via pathways that are specific to the precursor, which
      makes TA proteins a model system for investigating post-translational protein
      targeting. Bioinformatics approaches have previously been used to identify
      potential TA proteins in yeast and humans, yet little is known about TA proteins
      in plants. The identification of plant TA proteins is important for extending the
      post-translational model system to plastids, in addition to general proteome
      characterization, and the identification of functional homologues characterized
      in other organisms. We identified 454 loci that potentially encode TA proteins in
      Arabidopsis, and combined published data with new localization experiments to
      assign localizations to 130 proteins, including 29 associated with plastids. By
      analysing the tail anchor sequences of characterized proteins, we have developed
      a tool for predicting localization and estimate that 138 TA proteins are
      localized to plastids.

PMID- 19843282
TI  - Bulk flow revisited: transport of a soluble protein in the secretory pathway.
AB  - The C-terminal domain, Cp, of the Semliki Forest virus capsid protein, known for
      its rapid, efficient and chaperone-independent folding, was used to measure bulk
      fluid flow in the secretory pathway of Chinese hamster ovary cells. Being small,
      nonglycosylated, soluble and cytoplasmic in origin, Cp was not likely to interact
      with lectins, cargo receptors and retention factors. Using pulse-chase analysis,
      we observed that translocation into the endoplasmic reticulum resulted in rapid
      and efficient folding and transport of the newly synthesized Cp protein to the
      extracellular medium. The first Cp molecules were secreted 15 min after
      synthesis, which is the fastest transport of a protein so far recorded in
      mammalian cells. The rate constant of secretion was 1.2% per min, which amounts
      to an estimated bulk flow rate of about 155 coat protein II (COPII) vesicles per
      second. Transport was independent of expression level, and blocked by CI-976,
      brefeldin A and ATP depletion indicating that it depended on COPII vesicle
      formation, and followed the classical secretory pathway. In polarized Madin-Darby
      canine kidney cells, the secretion rate was similar but occurred mainly apically.
      The results demonstrated that fluid flow in the secretory pathway is fast, and
      can therefore play a significant role in the secretion of soluble secretory
      products.

PMID- 19843283
TI  - TRAPP II complex assembly requires Trs33 or Trs65.
AB  - TRAPP is a multi-subunit complex that acts as a Ypt/Rab activator at the Golgi
      apparatus. TRAPP exists in two forms: TRAPP I is comprised of five essential and
      conserved subunits and TRAPP II contains two additional essential and conserved
      subunits, Trs120 and Trs130. Previously, we have shown that Trs65, a nonessential
      fungi-specific TRAPP subunit, plays a role in TRAPP II assembly. TRS33 encodes
      another nonessential but conserved TRAPP subunit whose function is not known.
      Here, we show that one of these two subunits, nonessential individually, is
      required for TRAPP II assembly. Trs33 and Trs65 share sequence, intracellular
      localization and interaction similarities. Specifically, Trs33 interacts
      genetically with both Trs120 and Trs130 and physically with Trs120. In addition,
      trs33 mutant cells contain lower levels of TRAPP II and exhibit aberrant
      localization of the Golgi Ypts. Together, our results indicate that in yeast,
      TRAPP II assembly is an essential process that can be accomplished by either of
      two related TRAPP subunits. Moreover, because humans express two Trs33
      homologues, we propose that the requirement of Trs33 for TRAPP II assembly is
      conserved from yeast to humans.

PMID- 19843284
TI  - Relative safety of first-time volunteer and replacement donors in West Africa.
AB  - BACKGROUND: A significantly higher level of safety between nonremunerated
      volunteer and replacement donor blood is assumed. This is supported by global
      data without stratifying between genuine replacement and paid donors, for first
      time or repeat volunteer, or according to age. STUDY DESIGN AND METHODS: In 2008,
      first-time volunteer and replacement donors were identified, and confirmed human
      immunodeficiency virus antibody (anti-HIV), hepatitis B surface antigen (HBsAg),
      and hepatitis C virus antibody (anti-HCV)-positive screening results were
      collated. Data were analyzed according to age and sex between the two types of
      donors. RESULTS: In 6640 first-time volunteer and 4360 replacement donors, the
      prevalence of anti-HIV and HBsAg (1.03 and 13.8% vs. 1.1 and 14.9%, respectively)
      was not significantly different. Anti-HIV prevalence was higher in replacement
      donors less than age 20 than in first-time volunteers; the difference was not
      significant. HBsAg and anti-HIV confirmed-positive prevalence was significantly
      higher in first-time volunteer donors over age 20. CONCLUSION: In Kumasi, Ghana,
      viral safety of replacement and first-time volunteer donors was similar,
      constituting a single population of donors. Safety increment is provided by
      repeat donation applicable to either group, through different approaches. A blood
      unit from replacement donor costs half or less than that from a volunteer donor;
      similar studies conducted elsewhere in sub-Saharan Africa may lead to changes in
      current strategies.

PMID- 19843285
TI  - Moderate and severe adverse events associated with apheresis donations:
      incidences and risk factors.
AB  - BACKGROUND: The goal of this observational retrospective study was to evaluate
      various donor and procedural variables as potential risk factors for different
      types of moderate to severe adverse events (AEs) during apheresis collections.
      STUDY DESIGN AND METHODS: Data on all apheresis collections performed on Trima
      Accel (TA; CaridianBCT) instruments over a 28-month period were extracted from a
      donor database (Vista Information System, CaridianBCT) and reviewed along with AE
      reports from the same period. Donor and procedural variables were compared among
      uneventful procedures and those that resulted in various types of moderate to
      severe AEs, including presyncopal or syncopal (PS) episodes, citrate reactions
      (CR), reactions with both components (PS + CR), and self-reported incidents of
      significant venipuncture-related vascular injuries (VIs). RESULTS: A total of 59
      moderate to severe AEs occurred among 15,763 procedures (0.37%), including 19 PS,
      4 CR, 17 PS + CR, 12 VI, and 7 miscellaneous reactions. Greater blood loss and
      lower net fluid balance were associated with PS; female sex, older age, and
      smaller total blood volume (TBV) were associated with CR; and development of VI
      may be associated with female sex and smaller TBV. Younger age was not a risk
      factor for AEs. CONCLUSIONS: Apheresis collections performed by TA instruments
      are safe with a low incidence of significant AEs. Various types of AEs have
      different predisposing factors. Apheresis may be a safer option for donors with
      risk factors for PS reactions associated with whole blood collections, such as
      younger age, female sex, and small TBV.

PMID- 19843286
TI  - Scrub typhus induced by peripheral blood stem cell transplantation in the
      immunocompromised patient: diagnostic usefulness of nested polymerase chain
      reaction.
AB  - Scrub typhus (Orientia tsutsugamushi) is a Gram-negative rickettsial disease in
      parts of Asia, transmitted from wild rodents to human by mites. This is a case
      report of scrub typhus contraction in an acute leukemia patient by transfusion of
      peripheral blood stem cells collected during the incubation period. Although
      human-to-human transmission of scrub typhus by needle-stick injury or
      transplacental transmission has previously been reported, this is the first case
      confirmed by polymerase chain reaction (PCR) and DNA sequencing. This type of
      incident shows the need to heighten awareness of the threat of rickettsial agents
      in transfused blood. Nested PCR is a useful diagnostic method to confirm the
      diagnosis during incubation period and in the early phase of disease, especially
      for immunocompromised patients.

PMID- 19843287
TI  - Plasma and cryoprecipitate manufactured from whole blood held overnight at room
      temperature meet quality standards.
AB  - BACKGROUND: With buffy coat (BC) processing of whole blood (WB) donations, the
      preparation of plasma occurs within 24 hours rather than 8 hours of collection.
      The effect of this change on coagulation factor function in plasma and
      cryoprecipitate was evaluated during the validation of this production method and
      with routine production. STUDY DESIGN AND METHODS: Plasma frozen after an
      overnight hold of WB was prepared via BC or whole blood filtration (WBF) methods
      and quality control (QC) variables were measured. Additionally, plasma prepared
      with the BC method was compared to plasma produced using the platelet-rich plasma
      (PRP) method with an extended plasma factor analysis. Selected plasma factor
      levels were also measured in both cryoprecipitate and cryosupernatant plasma
      prepared using the WBF method from plasma frozen on the day of collection or
      after an overnight hold of WB. RESULTS: When comparing BC plasma to PRP plasma,
      coagulation factors (F)II, VII, VIII, IX, X, and XI had somewhat lower levels,
      and fibrinogen and antithrombin levels were elevated. As expected the most
      sensitive to the prolongation of production time was FVIII with 72 and 78% of the
      activity of PRP plasma and cryoprecipitate, respectively. However, both still met
      QC standards. Similarly, products made in routine production show acceptable
      levels of FVIII. CONCLUSION: Plasma and cryoprecipitate products, prepared using
      methods in which the plasma is frozen close to 24 hours after collection, meet
      current quality standards. The longer WB storage time has been implemented into
      general use in Canada.

PMID- 19843288
TI  - Immunomonitoring of graft-versus-host minor histocompatibility antigen correlates
      with graft-versus-host disease and absence of relapse after graft.
AB  - BACKGROUND: After HLA-identical hematopoietic stem cell transplantation, minor
      histocompatibility (mH) antigen alloreactivity plays a dominant role in the
      development of graft-versus-host disease (GVHD) and graft versus leukemia (GVL).
      STUDY DESIGN AND METHODS: We have analyzed the mH alloreactivity (enzyme-linked
      immunospot [ELISpot] for interferon-gamma[IFN-gamma] assay) from 24
      donor/recipient pairs over a period of 2 years of follow-up and correlated such
      alloreactivity with the development of GVHD or absence of relapse. Circulating
      specific T cells anti-mH with multimer HLA-peptides were also studied. RESULTS:
      We show by ELISpot IFN-gamma assay that alloreactivity during the first 3 months
      from donor versus recipient or donor versus mismatched identified mH antigens is
      associated with acute GVHD and GVL effect. In addition, we demonstrate that the
      donor-versus-recipient reactivity observed after the third month is highly
      associated with chronic GVHD and GVL (p = 0.0007). Finally, we show by multimer
      HLA-peptide assay that mH epitope-specific T cells present after 3 months are
      statistically related to the GVL effect. CONCLUSIONS: Our results provide a
      robust method to monitor mH antigen graft-versus-host reaction and suggest that
      current identified mH have predictive value on GVHD and GVL.

PMID- 19843289
TI  - Increase in CD230 (cellular prion protein) fluorescence on blood lymphocytes in
      bovine spongiform encephalopathy-infected nonhuman primates.
AB  - BACKGROUND: The cellular prion protein (PrP(c)) plays a central role in prion
      diseases such as variant Creutzfeldt-Jakob disease. This disease can be
      transmitted by blood transfusion. However, the exact kinetics of blood
      infectivity and the blood fraction carrying infectivity have not yet been
      identified. STUDY DESIGN AND METHODS: Simian PrP(c) epitopes were mapped by flow
      cytometry using monoclonal antibodies (MoAbs). A whole blood/no wash protocol was
      established, validated, and applied to investigate peripheral blood cell
      associated PrP(c) expression profiles in bovine spongiform encephalopathy (BSE)
      infected cynomolgus monkeys and age-/sex-matched controls. In addition,
      physiologic expression patterns on blood cells and in lymphoid tissues were
      determined. RESULTS: In BSE-infected macaques, blood lymphocyte-associated PrP(c)
      fluorescence gradually increased years before the onset of clinical signs (p(F
      test) < 0.0001). The increase in fluorescence intensity was detectable with MoAb
      12F10, whereas we failed to detect an increase with 3F4. In parallel, plasma
      concentrations of soluble CD230 also increased. Centrifugation of lymphocytes
      almost completely eliminated differences between infected and noninfected
      animals, most likely caused by a partial loss in cell-associated CD230 into the
      plasma supernatant. CONCLUSION: Blood lymphocytes from asymptomatically infected
      as well as diseased macaques were characterized by increased CD230 fluorescence,
      and phosphatidylinositol-phospholipase C-resistant PrP molecules contributed at
      least partially to this increase. Conformational changes within PrP(c) molecules
      may be the underlying mechanism for the increased PrP(c) fluorescence. This cell
      associated phenomenon contributed at least partially to an increase in soluble
      plasma-derived PrP(c) levels. It is not yet known whether these changes reflect
      infectivity.

PMID- 19843290
TI  - The risk of transfusion-transmitted infections in sub-Saharan Africa.
AB  - BACKGROUND: Blood transfusions carry the risk of transmitting infections. This
      risk has been studied in detail in high-income countries but not in sub-Saharan
      Africa. This study estimates the risks of acquiring human immunodeficiency virus
      (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) from a single unit of
      blood in sub-Saharan Africa. STUDY DESIGN AND METHODS: A mathematical model was
      constructed to quantify transfusion risks across 45 sub-Saharan African countries
      using three components: the risk of a contaminated unit entering the blood
      supply, the risk that the unit will be given to a susceptible patient, and the
      risk that receipt of the unit will lead to infection in the recipient. Variables
      included prevalence of infection in donors, extent of blood testing, test
      sensitivity, and susceptibility of recipients. Data from the World Health
      Organization (WHO) African Region and a systematic review of the literature were
      used to parameterize the model. Uncertainty in the risk estimates was quantified
      using probabilistic sensitivity analysis. RESULTS: The median overall risks of
      becoming infected with HIV, HBV, and HCV from a blood transfusion in sub-Saharan
      Africa were 1, 4.3, and 2.5 infections per 1000 units, respectively. If annual
      transfusion requirements projected by the WHO were met, transfusions alone would
      be responsible for 28,595 HBV infections, 16,625 HCV infections, and 6650 HIV
      infections every year. Sensitivity analysis suggests that the true risks may be
      even higher. CONCLUSIONS: This study is the first to systematically quantify the
      risks of transfusion-transmitted infections across sub-Saharan Africa. Although
      the results are limited by the quality and quantity of available data, these may
      be the most reliable estimates at this time.

PMID- 19843291
TI  - Life-threatening hemolytic anemia due to an autoanti-Pr cold agglutinin: evidence
      that glycophorin A antibodies may induce lipid bilayer exposure and cation
      permeability independent of agglutination.
AB  - BACKGROUND: The hemoglobin of a 29-year-old man fell below 35 g/L over 5 days,
      despite 14 units of red blood cells (RBCs), due to an anti-Pr cold agglutinin
      (CA). His hemolytic anemia necessitated respiratory support in intensive care for
      4 weeks. STUDY DESIGN AND METHODS: The hemolysis was investigated by the effects
      on blood group-compatible RBCs of this anti-Pr and an anti-I CA and of a rabbit
      anti-human glycophorin A (GPA) immunoglobulin G (IgG) antibody on Ca(2+)
      permeability and of phosphatidylethanolamine (PE) exposure. 1) The anti-Pr CA (in
      a plasmapheresis product from the patient) was absorbed and eluted from RBC
      ghosts and its immunophenotype was determined by agarose electrophoresis and
      immunofixation. 2) Ca(2+) permeability was measured by the response of Fluo-3
      labeled RBCs to addition of external Ca(2+). 3) Exposed PE was measured with
      streptavidin-labeled biotinylated peptide Ro 09-0198 (cinnamycin). RESULTS: 1)
      The patient's anti-Pr CA was a polyclonal IgG. 2) The anti-Pr and the rabbit anti
      human glycophorin IgG, but not an anti-I CA, rapidly increased Ca(2+)-dependent
      fluorescence upon addition of external Ca(2+) in a fraction (15%-25%) of RBCs
      that also became positive for cinnamycin. 3) Trypsin treatment of RBCs reduced
      the Ca(2+) influx due to the anti-Pr IgG, but neither trypsin nor neuraminidase
      changed the responses to the rabbit anti-human GPA IgG. CONCLUSIONS: The anti-Pr
      CA and rabbit anti-human GPA increased exposure of PE and increased membrane
      Ca(2+) permeability that may have caused hemolysis. The difference in the
      responses to these antibodies to enzyme treatment of RBCs suggests that they
      react with different epitopes on GPA.

PMID- 19843292
TI  - Comparison of higher dose and lower dose ganciclovir for cytomegalovirus
      prophylaxis in seropositive heart transplant recipients.
AB  - BACKGROUND: We performed a retrospective historical cohort study to compare the
      efficacy of higher dose (HD, 10 mg/kg/day for 2 weeks, followed by 5 mg/kg/day
      intravenously for 2 weeks) and lower dose (LD, 5 mg/kg/day for 4 weeks)
      ganciclovir (GCV) for cytomegalovirus (CMV) prophylaxis in seropositive heart
      transplant recipients. METHODS: All consecutive patients undergoing heart
      transplantation (HT) between June 1999 and January 2008 at our institution were
      enrolled. All recipients were seropositive for CMV before HT. Before October
      2005, 72 patients received the HD regimen and after October 2005, 36 patients
      received the LD regimen. We followed up all patients for 1 year. RESULTS: In the
      HD group 43 of 72 patients (60%) developed CMV infections vs. 21 of 36 patients
      (58%) in the LD group (P=0.89). CMV diseases occurred in 4 patients of the HD
      group (6%) and 4 patients of the LD group (11%) (P=0.44). The incidence of acute
      rejection was not significantly different between the 2 groups (14% vs. 6%;
      P=0.33). Among patients who completed 4-week courses of prophylaxis, 32 of 58
      patients (55%) in the HD group developed CMV infections vs. 18 of 30 patients
      (60%) in the LD group (P=0.66). CMV diseases occurred in 3 patients of the HD
      group (5%) and 4 of the LD group (13%) (P=0.22). Acute rejection incidence did
      not differ significantly between the 2 groups (17% vs. 7%; P=0.21). CONCLUSIONS:
      LD GCV for CMV prophylaxis may not be inferior to the HD regimen in seropositive
      HT recipients.

PMID- 19843293
TI  - Sirolimus monotherapy as maintenance immunosuppression: a multicenter experience.
AB  - The aim of this study was to retrospectively evaluate safety and feasibility of
      sirolimus (SRL) monotherapy in kidney transplant recipients. Patients older than
      18 years, with monotherapy prescribed for more than 1 month and at least 6 months
      of follow-up were included. We analysed the data from 138 patients. Mean time
      period between transplantation and start of monotherapy was 6.5 +/- 4.1 years.The
      most frequent reason was minimization of immunosuppression followed by
      malignancy. Acute rejection rate was 1.4% at 12 months (two episodes). Graft and
      patient survival were 94.2% and 97.1% respectively. Mean follow-up after
      initiation of monotherapy was 29.4 months. Two patients died as a result of
      cardiovascular diseases and two because of malignancy. Percentage of withdrawal
      from monotherapy was 14%. SRL trough levels were 10.2 +/- 2.3 ng/ml at baseline
      and 9.6 6 +/- 3.3 ng/ml at 12 months. Mean glomerular filtration rate was 48.4
      ml/min/1.73 m(2) at baseline and 47.7 ml/min/1.73 m(2) at 12 months. Proteinuria
      was 499.7 mg/24 h at baseline and 543 +/- 794 mg/24 h at 12 months. No
      significant changes in lipids, glucose, or hemoglobin occurred, although the
      percentage of patients treated with statins and Epo increased at the end of the
      follow-up. SRL monotherapy is suitable as long-term immunosuppression in selected
      patients with no significantly increased risk of late acute rejection.

PMID- 19843294
TI  - Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma.
AB  - About 20% of the patients with advanced hepatocellular carcinoma (HCC) who are
      listed for liver transplantation (LT) are eventually delisted as a result of
      local tumor progression. Herein, we report our experience with conformal
      radiotherapy (CRT) as a novel bridge to LT. From July 2006 to August 2008, CRT
      was delivered in five or six fractions to patients with HCC listed for LT in whom
      either prior local therapies had failed or those not suitable for standard local
      therapies because of poor liver function or anatomic issues. Radiotherapy (RT)
      volumes and doses were individualized to spare the uninvolved liver with the goal
      of stabilizing the most aggressive HCC(s) in an attempt to reduce the chance of
      delisting as a result of tumor progression. Ten patients with tumor diameters
      ranging from 25 to 108 mm were treated. Eight out of 10 tumors were beyond Milan
      criteria. The median age was 55 (range 36-64). Seventy percent of the patients
      were male subjects. The median medical MELD score was 11 (range 9-17). The median
      irradiated HCC volume was 79 cc (range 15-798 cc). The median RT delivered dose
      was 33 Gy (range 8.5-54 Gy), in one to six fractions. The median dose to the
      uninvolved liver was 13.3 Gy (range 1.8-16.5). Nine patients completed their CRT
      as planned and one patient was transplanted after the first fraction. The
      treatment was well tolerated: Grade 1 nausea was reported in three patients, the
      platelet count decreased from 154 to 98 in one patient, and there were no other
      complications. No treated tumors progressed during or after the treatment. Two
      tumors remained stable; the rest had 10-50% regression, which was sustained on
      follow-up imaging. The median follow up was 14 months (range 3-20). Local tumor
      control was achieved in all treated tumors.Two patients were delisted as a result
      of cancer progression outside the treated field (one in the context of systemic
      metastases; yet another with progression of other untreated HCC in the liver).
      Three patients are still waiting for transplantation. Five patients underwent LT
      with no complications attributable to the CRT. Explant pathology, available for
      five patients, showed tumor necrosis and fibrosis with sparing of the untreated
      parenchyma. All transplanted patients treated with CRT are cancer-free. CRT is a
      safe and efficacious local bridging therapy for patients with advanced HCC who
      are on the waiting list for LT. Further studies are warranted to compare the
      effectiveness of CRT to other local treatment regimens for HCC.

PMID- 19843295
TI  - New prediction factors of small-for-size syndrome in living donor adult liver
      transplantation for chronic liver disease.
AB  - Small-for-size syndrome (SFSS), which is characterized by synthetic dysfunction
      and prolonged cholestasis, is a major cause of worse short-term prognoses after
      living donor adult liver transplantation (LDALT). However, the risks of SFSS
      remain unclear. The aim of this study was to clarify the risks of SFSS, which
      were analysed in 172 patients who underwent LDALT for chronic liver disease.
      Graft types included left lobe with caudate lobe graft (n = 110) and right lobe
      graft (n = 62). Thirty-four cases (24 with left lobe grafts and 10 with right
      lobe grafts) were determined as SFSS. SFSS developed even if the actual graft-to
      recipient standard liver volume ratio was >40%. Logistic regression analysis
      revealed three independent factors associated with SFSS development in left and
      right lobe grafts: donor age, actual graft-to-recipient native liver volume
      ratio, and Child's score. Donor age and actual graft-to-recipient native liver
      volume ratio may become predictive factors for SFSS development in left and right
      lobe grafts in patients undergoing LDALT.

PMID- 19843296
TI  - Corticosteroid avoidance in adult kidney transplant recipients under rabbit anti
      T-lymphocyte globulin, mycophenolate mofetil and delayed cyclosporine
      microemulsion introduction.
AB  - We conducted the first prospective, randomized, open-label multicenter study in
      low-immunologic risk adult recipients of primary cadaver kidney transplants
      receiving rabbit anti-T-lymphocyte globulin, mycophenolate mofetil, cyclosporine
      microemulsion introduced on day 5, with and without corticosteroids. Patients
      were randomly assigned according to age and cold ischemia time to receive
      corticosteroids for at least 6 months or no corticosteroids at all. The main
      efficacy evaluation criterion was acute rejection (including all treated episodes
      and those biopsy-confirmed) during the first year following transplantation. For
      this purpose, this report includes the actual results of the whole 12-month
      follow-up of all randomized patients. For efficacy analysis, 98 patients were
      evaluated in the Steroid avoidance group and 99 in the Steroid maintenance group.
      Taken as a whole, 81% of the patients (n = 159) never received anti-rejection
      treatment. From the 38 patients who received anti-rejection treatment, 25 (25.5%)
      were in the Steroid avoidance group and 13 (13.1%) in the Steroid maintenance
      group (P < 0.031), experiencing respectively 17 (17.3%) and 7 (7.1%) biopsy
      proven first episodes of acute rejection (P < 0.031). Borderline changes (6 vs.
      3) were not considered as biopsy-proven acute rejections. Onset of first
      rejection was significantly shorter in the Steroid avoidance group (P < 0.027).
      First-line anti-rejection treatment response, need for any rescue therapy, as
      well as histologic severity of rejection episodes did not statistically differ
      between the groups. One-year post-transplantation analysis showed no differences
      in delayed graft function, serum creatinine, creatinine clearance, 24-h
      proteinuria, as well as serious adverse events between the groups. De novo
      diabetes (P < 0.07) or dyslipidemia (P < 0.01) as well as newly diagnosed
      malignancies (P < 0.059) were however more frequently observed in the Steroid
      maintenance group. At the end of the first post-transplant year, 99% of patients
      in the Steroid avoidance group and 97% of patients in the Steroid maintenance
      group were respectively alive (P = 0.34), with respectively 95% and 93.2% of
      functioning kidney grafts (P = 0.62). Our results showed that total avoidance of
      corticosteroids from the day of transplantation was associated with a
      significantly increased number of clinically diagnosed and treated, and biopsy
      proven acute rejections during the first year of transplantation. Nevertheless,
      overall outcome, 1-year patient and graft survival as well as renal function were
      similar, and the patients in the Steroid avoidance group exhibited a lower
      incidence of de novo dyslipidemia, diabetes mellitus and malignancies often
      associated with steroid treatment.

PMID- 19843297
TI  - Hepatitis B treatment in resource poor settings: time for action.
AB  - Chronic hepatitis B virus infection is common cause of morbidity and mortality in
      resource poor settings. Now that effective drugs are available, international
      action is needed to implement treatment programmes.

PMID- 19843298
TI  - Default during TB diagnosis: quantifying the problem.
AB  - OBJECTIVES: To quantify default during diagnosis in TB suspects and in smear
      positive cases; to investigate sex differences in default during diagnosis, in
      all of Pakistan. METHODS: Data from laboratory registers were collected on 12 216
      suspects in nine districts over the period July-September 2008. RESULTS: A total
      of 1573 TB suspects (12.9%, 95% CI = 12.3-13.5) dropped out of the diagnostic
      process after initial sputum submission. A total of 2058 smear-positive cases
      were detected, and of these 107 (5.2%, 95% CI = 4.2-6.2) defaulted during
      diagnosis and therefore could not be started on treatment. Male suspects
      defaulted slightly more frequently than female suspects (P = 0.0268). CONCLUSION:
      Default during diagnosis is a frequent occurrence in Pakistan that should be
      monitored and addressed by TB control programs.

PMID- 19843299
TI  - Prevalence and significance of extracellular myelin-like material in canine
      cerebrospinal fluid.
AB  - BACKGROUND: Myelin-like material in canine cerebrospinal fluid (CSF) specimens
      has been attributed to demyelinating or myelomalacic conditions. In our
      experience, myelin-like material is observed frequently, especially in lumbar
      samples, and in a variety of disease conditions. OBJECTIVES: The objective of
      this study was to determine if there are associations between the presence of
      myelin-like material and CSF collection site, body weight, underlying disease,
      and patient outcome. METHODS: Wright-Giemsa-stained cytocentrifuged specimens of
      CSF from the cerebellomedullary cistern (n=51) and lumbar cistern (n=47) of 98
      dogs with neurologic disease were evaluated retrospectively for the presence and
      amount of extracellular myelin-like material. Results were compared based on
      collection site, body weight, type of neurologic disease, and outcome. RESULTS:
      Myelin-like material was observed in 20/98 (20%) samples and was more frequently
      observed in lumbar (17/47, 36%) than cerebellomedullary samples (3/51, 6%)
      (P=.0028). Samples from dogs <10 kg were more likely to contain myelin (14/36,
      39%) compared with dogs > or =10 kg (5/60, 8%) (P=.0052). Larger amounts of
      myelin-like material were observed in CSF from dogs with intervertebral disk
      disease compared with other diseases (P=.045). No association was found between
      myelin-like material and outcome. CONCLUSION: The association of extracellular
      myelin-like material in canine CSF samples with sampling site and body weight
      suggests it is more often an artifact of collection technique and anatomy rather
      than the result of neurologic disease. Myelin-like material in CSF is not
      associated with a poorer prognosis.

PMID- 19843301
TI  - Cutaneous epitheliotropic T-cell lymphoma with dissemination to the liver in an
      eastern chipmunk (Tamias striatus).
AB  - Cutaneous epitheliotropic T-cell lymphoma with liver metastasis was diagnosed in
      a 10-year-old eastern chipmunk (Tamias striatus). Physical findings included
      intracutaneous swellings, ulcerated plaques and nodules, hypotrichosis and
      erythema of the skin. Fine needle aspiration from the skin lesions showed a
      population of large lymphocytes and lymphoblasts, and was helpful in establishing
      the diagnosis antemortem. The post-mortem examination revealed epitheliotropic
      lymphoma with liver metastasis. Immunohistochemistry proved the T-cell origin
      both in the liver and skin tumours. Electron microscopy did not reveal any viral
      particles within the tumour. To the authors' knowledge, this is the first case of
      lymphoma described in this species.

PMID- 19843300
TI  - Pseudomonas fluorescens contamination of a feline packed red blood cell unit and
      studies of canine units.
AB  - BACKGROUND: While screening programs have reduced the risk of infectious disease
      transmission by donors in human and veterinary blood banking, bacterial
      contamination of blood products has emerged as a major complication in human
      medicine. OBJECTIVES: To describe a Pseudomonas fluorescens (Pf)-contaminated
      feline packed RBC (pRBC) unit and experimentally investigate Pf-contaminated
      canine pRBCs. METHODS: Canine pRBCs were inoculated with Pf-rich pRBCs from the
      sentinel feline unit and stored at 4 degrees C or 20 degrees C for 72 hours.
      Aliquots from the pRBCs were serially evaluated by microscopy, culture, and a
      eubacterial 16S rRNA real-time PCR assay. RESULTS: One Pf-contaminated feline
      unit turned black after 22 days of storage and was removed from the blood bank; a
      source was not found, and no other contaminated units were identified. Canine
      pRBCs spiked with 5 or 25 microL of the sentinel unit became culture- and/or 16S
      PCR-positive at > or =8 hours at 20 degrees C and 48 hours at 4 degrees C and
      developed a color change at > or =24 hours. Sensitivity studies indicated that
      without incubation, inoculation of > or =100 microL Pf-rich pRBCs was necessary
      for a positive 16S PCR test result. CONCLUSIONS: P. fluorescens grows in stored
      pRBCs slowly at 4 degrees C and rapidly at 20 degrees C. Screening of blood
      products for color change, estimating bacterial concentration with microscopy,
      and 16S PCR testing are simple and fast ways to detect bacteria in stored blood.
      Aseptic collection, temperature-controlled storage, and regular visual monitoring
      of stored units is recommended. Discolored units should not be transfused, but
      examined for bacterial contamination or other blood product quality problems.

PMID- 19843302
TI  - A randomized, double-blind, placebo-controlled study to evaluate the effect of
      EFF1001, an Actinidia arguta (hardy kiwi) preparation, on CADESI score and
      pruritus in dogs with mild to moderate atopic dermatitis.
AB  - Canine atopic dermatitis (AD) is common and new therapies are beneficial. This
      multicentric, randomized, double-blind, placebo-controlled study tested the
      efficacy of Actinidia arguta (hardy kiwi) (EFF1001) in dogs with mild/moderate
      AD. The study was divided into two stages. Stage 1 lasted 6 weeks. In the first 2
      weeks prednisolone [days 1-3: 0.2 mg/kg twice daily (BID), days 4-14: 0.2 mg/kg
      every other day (EOD)] was administered. Responsive dogs were placed on
      prednisolone 0.2 mg/kg EOD + assigned test article [either placebo or EFF1001 (30
      mg/kg)] once daily for 4 weeks. Stage 1 responders were advanced to stage 2,
      which involved 4 weeks of just EFF1001. Clinicians scored lesions using Canine
      Atopic Dermatitis Extent and Severity Index (CADESI) and owners scored pruritus
      using a Pruritus Visual Analogue Scale. Seventy-seven dogs were enrolled, 76 were
      randomized on day 14, and 57 (57/76 = 75%) completed stage 1 (27 in EFF1001 and
      30 in placebo). At the end of stage 1, 35 of 57 dogs (35/57 = 61%) responded (18
      in EFF1001 and 17 in placebo) and advanced to stage 2. At completion of stage 1,
      CADESI scores did not significantly differ between groups while pruritus
      decreased in EFF1001 group and approached significance. At completion of stage 2,
      19 dogs (19/35 = 54%) responded (15/19 = 79% had received EFF1001 and 4/19 = 21%
      placebo in stage 1). After completing stage 2, dogs placed on EFF1001 throughout
      the study were 3.5 times more likely to either maintain or improve scores than
      those that started it in stage 2. It is concluded that EFF1001 is beneficial
      adjunctive therapy after prolonged use.

PMID- 19843303
TI  - Comprehensive polymorphism analysis of ABO using allele-specific separation by
      bead technology and subsequent sequencing.
AB  - The ABO system is the most important blood group system in transfusion and
      transplantation medicine. Over the last decade ABO genotyping was introduced to
      complement serological analysis but because of the enormous diversity at the ABO
      locus, DNA-based typing is highly sophisticated. In some genotype combinations
      and especially when dealing with hybrid genes, cis/trans linkage analysis is
      necessary. Therefore, we developed a simple and reliable approach to isolate ABO
      haplotypes. The described method physically separates diploid genomic DNA using
      probe-dependent allele hybridization followed by magnetic bead separation. After
      this haplotype-specific extraction (HSE), sequencing based typing (SBT) was
      performed to analyze coding and non-coding respectively regulatory regions of
      ABO.

PMID- 19843304
TI  - Transcriptional regulation of metal transport genes and mineral nutrition during
      acclimatization to cadmium and zinc in the Cd/Zn hyperaccumulator, Thlaspi
      caerulescens (Ganges population).
AB  - We investigated changes in mineral nutrient uptake and cellular expression levels
      for metal transporter genes in the cadmium (Cd)/zinc (Zn) hyperaccumulator,
      Thlaspi caerulescens during whole plant and leaf ontogenesis under different long
      term treatments with Zn and Cd. Quantitative mRNA in situ hybridization (QISH)
      revealed that transporter gene expression changes not only dependent on metal
      nutrition/toxicity, but even more so during plant and leaf development. The main
      mRNA abundances found were: ZNT1, mature leaves of young plants; ZNT5, young
      leaves of young plants; MTP1 (= ZTP1 = ZAT), young leaves of both young and
      mature plants. Surprisingly different cellular expression patterns were found for
      ZNT1 and ZNT5, both belonging to the ZIP family of transition metal transporters:
      ZNT1, photosynthetic mesophyll and bundle sheath cells; ZNT5, nonphotosynthetic
      epidermal metal storage cells and bundle sheath cells. Thus, ZNT1 may function in
      micronutrient nutrition while ZNT5 may be involved in metal storage associated
      with hyperaccumulation. Cadmium inhibited the uptake of Zn, iron (Fe) and
      manganese (Mn), probably by competing for transporters or by interfering with the
      regulation of transporter gene expression. Cadmium-induced changes in cellular
      expression for ZNT1, ZNT5 and MTP1 could also be part of plant acclimatization to
      Cd toxicity. Defence against Cd toxicity involved enhanced uptake of magnesium
      (Mg), calcium (Ca) and sulphur (S).

PMID- 19843305
TI  - Drought effects on allocation of recent carbon: from beech leaves to soil CO2
      efflux.
AB  - *Recent studies have highlighted a direct, fast transfer of recently assimilated
      C from the tree canopy to the soil. However, the effect of environmental changes
      on this flux remains largely unknown. *We investigated the effects of drought on
      the translocation of recently assimilated C, by pulse-labelling 1.5-yr-old beech
      tree mesocosms with (13)CO(2). (13)C signatures were then measured daily for 1 wk
      in leaves, twigs, coarse and fine root water-soluble and total organic matter,
      phloem organic matter, soil microbial biomass and soil CO(2) efflux. *Drought
      reduced C assimilation and doubled the residence time of recently assimilated C
      in leaf biomass. In phloem organic matter, the (13)C label peaked immediately
      after labelling then decayed exponentially in the control treatment, while under
      drought it peaked 4 d after labelling. In soil microbial biomass, the label
      peaked 1 d after labelling in the control treatment, whereas under drought no
      peak was measured. Two days after labelling, drought decreased the contribution
      of recently assimilated C to soil CO(2) efflux by 33%. *Our study showed that
      drought reduced the coupling between canopy photosynthesis and belowground
      processes. This will probably affect soil biogeochemical cycling, with potential
      consequences including slower soil nitrogen cycling and changes in C
      sequestration potential under future climate conditions.

PMID- 19843306
TI  - The synergistic activity of triclosan and ciprofloxacin on biofilms of Salmonella
      Typhimurium.
AB  - Triclosan is a biocide whose wide use has raised a debate about the potential
      benefits vs. hazards of the incorporation of antimicrobials in consumer products.
      The purpose of the present study was to determine whether exposure of biofilms of
      Salmonella enterica serovar Typhimurium to triclosan influences the tolerance of
      the bacteria towards antibiotics such as ciprofloxacin and vice versa. A
      synergistic antibiofilm activity was observed when the biofilms were treated with
      triclosan before or together with ciprofloxacin, and an additive activity was
      observed with planktonic cells. For example 500 microg mL(-1) triclosan and 500
      microg mL(-1) ciprofloxacin reduced the number of viable cells in the biofilm by
      1.6 and 0.5 log, respectively. However, the sequential treatment of 500 microg
      mL(-1) triclosan followed by ciprofloxacin resulted in 4.8 log reduction.
      Combination indexes (CI) for biofilms treated with triclosan followed by
      ciprofloxacin were 0.7, 0.32 and 0.25 for reduction of 90%, 99% and 99.9%,
      respectively, indicating a synergism. For planktonic cells, CIs were 1+/-0.1,
      indicating an additive effect. Therefore, it was suggested that triclosan weakens
      the ability of biofilm-associated cells to survive exposure to ciprofloxacin in
      the biofilm, probably by improving the permeability or the activity of
      ciprofloxacin.

PMID- 19843307
TI  - Identification of Salmonella enterica subspecies I, Salmonella enterica serovars
      Typhimurium, Enteritidis and Typhi using multiplex PCR.
AB  - This study was designed to develop a multiplex PCR method with five specific
      primer pairs for the detection of Salmonella spp., Salmonella subspecies I,
      Salmonella enterica serovars Typhimurium, Typhi and Enteritidis. A multiplex PCR
      was constructed with five primer pairs for the detection of Salmonella and
      pathogenic Salmonella serovars, including a specific primer pair for Salmonella
      Typhi, based on the sequence comparison between genomic DNA sequences of 12
      Salmonella strains. Each primer pair was specifically targeted to Salmonella
      spp., Salmonella subspecies I, Salmonella Typhimurium, Typhi and Enteritidis.
      This multiplex PCR was evaluated with various DNAs of Salmonella serovars that
      yielded high specificity for amplifying the expected PCR products of Salmonella
      serovars. Using this primer pair, a set of multiplex PCR was performed for the
      rapid identification of salmonellae and major pathogenic Salmonella serovars.
      Although this multiplex PCR method will need to be evaluated for a wide range of
      Salmonella serovars among multilaboratories, it should be useful for identifying
      clinically significant strains of Salmonella serovars rapidly and accurately
      without the need for serological testing.

PMID- 19843308
TI  - Cellulosic alcoholic fermentation using recombinant Saccharomyces cerevisiae
      engineered for the production of Clostridium cellulovorans endoglucanase and
      Saccharomycopsis fibuligera beta-glucosidase.
AB  - In this study, Saccharomyces cerevisiae was engineered for simultaneous
      saccharification and fermentation of cellulose by the overexpression of the
      endoglucanase D (EngD) from Clostridium cellulovorans and the beta-glucosidase
      (Bgl1) from Saccharomycopsis fibuligera. To promote secretion of the two enzymes,
      the genes were fused to the secretion signal of the S. cerevisiaealpha mating
      factor gene. The recombinant developed yeast could produce ethanol through
      simultaneous production of sufficient extracellular endoglucanase and beta
      glucosidase. When direct ethanol fermentation from 20 g L(-1)beta-glucan as a
      substrate was performed with our recombinant strains, the ethanol concentration
      reached 9.15 g L(-1) after 50 h of fermentation. The conversion ratio of ethanol
      from beta-glucan was 80.3% of the theoretical ethanol concentration produced from
      20 g L(-1)beta-glucan. In conclusion, we have demonstrated the construction of a
      yeast strain capable of conversion of a cellulosic substrate to ethanol,
      representing significant progress towards the realization of processing of
      cellulosic biomass in a consolidated bioprocessing configuration.

PMID- 19843309
TI  - Steroids mediate resistance to the bactericidal effect of phosphatidylcholines
      against Helicobacter pylori.
AB  - Helicobacter pylori assimilates various steroids as membrane lipid components,
      but it can also survive in the absence of steroids. It thus remains to be
      clarified as to why the organism relies on steroid physiologically. In this
      study, we have found that phosphatidylcholine carrying a linoleic acid molecule
      or arachidonic acid molecule has the potential to kill steroid-free H. pylori.
      The bactericidal action of phosphatidylcholines against H. pylori was due to the
      lytic activity of the phosphatidylcholines themselves and not due to the lytic
      activity of the unsaturated fatty acids or lyso-phosphatidylcholine resulting
      from the hydrolysis of the phosphatidylcholines. In contrast to the steroid-free
      H. pylori, the organism that absorbed and glucosylated free cholesterol was
      unaffected by the bactericidal action of the phosphatidylcholines. Similarly, H.
      pylori that absorbed estrone without glucosylating it also resisted the
      bactericidal action of the phosphatidylcholines. The steroids absorbed by H.
      pylori existed in both the outer and inner membranes, while the glucosyl-steroids
      produced via the steroid absorption were localized in the outer membrane rather
      than in the inner membrane. These results indicate that H. pylori absorbs the
      steroids to reinforce the membrane lipid barrier and thereby expresses resistance
      to the bacteriolytic action of hydrophobic compounds such as phosphatidylcholine.

PMID- 19843310
TI  - Adherence to host extracellular matrix and serum components by Enterococcus
      faecium isolates of diverse origin.
AB  - Enterococcus faecium has emerged as an important cause of nosocomial infections
      over the last two decades. We recently demonstrated collagen type I (CI) as a
      common adherence target for some E. faecium isolates and a significant
      correlation was found to exist between acm-mediated CI adherence and clinical
      origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to
      up to 15 immobilized host extracellular matrix and serum components. Adherence
      phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60
      isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the
      isolates adhered to collagen type V (CV), transferrin or lactoferrin and none to
      the other host components tested. Adherence to Fn and Ln was almost exclusively
      restricted to clinical isolates, especially the endocarditis-enriched nosocomial
      genogroup clonal complex 17 (CC17). Thus, the ability to adhere to Fn and Ln, in
      addition to CI, may have contributed to the emergence and adaptation of E.
      faecium, in particular CC17, as a nosocomial pathogen.

PMID- 19843311
TI  - The Ile13 residue of microcin J25 is essential for recognition by the receptor
      FhuA, but not by the inner membrane transporter SbmA.
AB  - Entry of the peptide antibiotic microcin J25 (MccJ25) into target cells is
      mediated by the outer membrane receptor FhuA and the inner membrane protein SbmA.
      The latter also transports MccB17 into the cell cytoplasm. Comparison of MccJ25
      and MccB17 revealed a tetrapeptide sequence (VGIG) common to both antibiotics. We
      speculated that this structural feature in MccJ25 could be a motif recognized by
      SbmA. To test this hypothesis, we used a MccJ25 variant in which the isoleucine
      in VGIG (position 13 in the MccJ25 sequence) was replaced by lysine (I13K). In
      experiments in which the FhuA receptor was bypassed, the substituted microcin
      showed an inhibitory activity similar to that of the wild-type peptide. Moreover,
      MccJ25 interfered with colicin M uptake by FhuA in a competition assay, while the
      I13K mutant did not. From these results, we propose that the Ile(13) residue is
      only required for interaction with FhuA, and that VGIG is not a major recognition
      element by SbmA.

PMID- 19843312
TI  - Cavotricuspid isthmus: anatomy, electrophysiology, and long-term outcome of
      radiofrequency ablation.
AB  - The cavotricuspid isthmus (CTI) had a complex architecture with an anisotropic
      conduction property. An incremental pacing from the low right atrial isthmus
      produced a conduction delay and block, and initiated atrial flutter.
      Radiofrequency catheter ablation of the CTI was very effective in eliminating the
      typical atrial flutter. However, atrial fibrillation often occurred after
      ablation of the isthmus and needs further treatment.

PMID- 19843313
TI  - Arabidopsis homolog of the yeast TREX-2 mRNA export complex: components and
      anchoring nucleoporin.
AB  - Nuclear pore complexes (NPCs) are vital to nuclear-cytoplasmic communication in
      eukaryotes. The yeast NPC-associated TREX-2 complex, also known as the Thp1-Sac3
      Cdc31-Sus1 complex, is anchored on the NPC via the nucleoporin Nup1, and is
      essential for mRNA export. Here we report the identification and characterization
      of the putative Arabidopsis thaliana TREX-2 complex and its anchoring
      nucleoporin. Physical and functional evidence support the identification of the
      Arabidopsis orthologs of yeast Thp1 and Nup1. Of three Arabidopsis homologs of
      yeast Sac3, two are putative TREX-2 components, but, surprisingly, none are
      required for mRNA export as they are in yeast. Physical association of the two
      Cdc31 homologs, but not the Sus1 homolog, with the TREX-2 complex was observed.
      In addition to identification of these TREX-2 components, direct interactions of
      the Arabidopsis homolog of DSS1, which is an established proteasome component in
      yeast and animals, with both the TREX-2 complex and the proteasome were observed.
      This suggests the possibility of a link between the two complexes. Thus this work
      has identified the putative Arabidopsis TREX-2 complex and provides a foundation
      for future studies of nuclear export in Arabidopsis.

PMID- 19843314
TI  - A protein phosphatase 2C, responsive to the bacterial effector AvrRpm1 but not to
      the AvrB effector, regulates defense responses in Arabidopsis.
AB  - Using a proteomics approach, a PP2C-type phosphatase (renamed PIA1, for PP2C
      induced by AvrRpm1) was identified that accumulates following infection by
      Pseudomonas syringae expressing the type III effector AvrRpm1, and subsequent
      activation of the corresponding plant NB-LRR disease resistance protein RPM1. No
      accumulation of PIA1 protein was seen following infection with P. syringae
      expressing AvrB, another type III effector that also activates RPM1, although PIA
      transcripts were observed. Accordingly, mutation of PIA1 resulted in enhanced
      RPM1 function in response to P. syringae pathover tomato (Pto) DC3000 (avrRpm1)
      but not to Pto DC3000 (avrB). Thus, PIA1 is a protein marker that distinguishes
      AvrRpm1- and AvrB-dependent activation of RPM1. AvrRpm1-induced expression of the
      pathogenesis-related genes PR1, PR2 and PR3, and salicylic acid accumulation were
      reduced in two pia1 mutants. By contrast, expression of other defense-related
      genes, including PR5 and PDF1.2 (plant defensin), was elevated in unchallenged
      pia1 mutants. Hence, PIA1 is required for AvrRpm1-induced responses, and confers
      dual (both positive and negative) regulation of defense gene expression.

PMID- 19843315
TI  - Arabidopsis plants lacking PsbS protein possess photoprotective energy
      dissipation.
AB  - It is commonly accepted that the photosystem II subunit S protein, PsbS, is
      required for the dissipation of excess light energy in a process termed 'non
      photochemical quenching' (NPQ). This process prevents photo-oxidative damage of
      photosystem II (PSII) thus avoiding photoinhibition which can decrease plant
      fitness and productivity. In this study Arabidopsis plants lacking PsbS (the npq4
      mutant) were found to possess a competent mechanism of excess energy dissipation
      that protects against photoinhibitory damage. The process works on a slower
      timescale, taking about 1 h to reach the same level of NPQ achieved in the wild
      type in just a few minutes. The NPQ in npq4 was found to display very similar
      characteristics to the fast NPQ in the wild type. Firstly, it prevented the
      irreversible light-induced closure of PSII reaction centres. Secondly, it was
      uncoupler-sensitive, and thus triggered by the DeltapH across the thylakoid
      membrane. Thirdly, it was accompanied by significant quenching of the
      fluorescence under conditions when all PSII reaction centres were open (F(o)
      state)(.) Fourthly, it was accompanied by NPQ-related absorption changes
      (DeltaA535). Finally, it was modulated by the presence of the xanthophyll cycle
      carotenoid zeaxanthin. The existence of a mechanism of photoprotective energy
      dissipation in plants lacking PsbS suggests that this protein plays the role of a
      kinetic modulator of the energy dissipation process in the PSII light-harvesting
      antenna, allowing plants to rapidly track fluctuations of light intensity in the
      environment, and is not the primary cause of NPQ or a direct carrier of the
      pigment acting as the non-photochemical quencher.

PMID- 19843316
TI  - Tissue layer specific regulation of leaf length and width in Arabidopsis as
      revealed by the cell autonomous action of ANGUSTIFOLIA.
AB  - In vascular plants the shoot apical meristem consists of three tissue layers, L1,
      L2 and the L3, that are kept separate during organ formation and give rise to the
      epidermis (L1) and the subepidermal tissues (L2, L3). For proper organ
      development these different tissue layers must interact with each other, though
      their relative contributions are a matter of debate. Here we use ANGUSTIFOLIA
      (AN), which controls cell polarity and leaf shape, to study its morphogenetic
      function in the epidermis and the subepidermis of Arabidopsis thaliana. We show
      that ANGUSTIFOLIA expression in the subepidermis cannot rescue epidermal cell
      polarity defects, indicating a cell-autonomous molecular function. We demonstrate
      that leaf width is only rescued by subepidermal AN expression, whereas leaf
      length is also rescued by epidermal expression. Strikingly, subepidermal rescue
      of leaf width is accompanied by increased cell number in the epidermis,
      indicating that AN can trigger cell divisions in a non-autonomous manner.

PMID- 19843318
TI  - Early vocabulary development in deaf native signers: a British Sign Language
      adaptation of the communicative development inventories.
AB  - BACKGROUND: There is a dearth of assessments of sign language development in
      young deaf children. This study gathered age-related scores from a sample of deaf
      native signing children using an adapted version of the MacArthur-Bates CDI
      (Fenson et al., 1994). METHOD: Parental reports on children's receptive and
      expressive signing were collected longitudinally on 29 deaf native British Sign
      Language (BSL) users, aged 8-36 months, yielding 146 datasets. RESULTS: A smooth
      upward growth curve was obtained for early vocabulary development and percentile
      scores were derived. In the main, receptive scores were in advance of expressive
      scores. No gender bias was observed. Correlational analysis identified factors
      associated with vocabulary development, including parental education and mothers'
      training in BSL. Individual children's profiles showed a range of development and
      some evidence of a growth spurt. Clinical and research issues relating to the
      measure are discussed. CONCLUSIONS: The study has developed a valid, reliable
      measure of vocabulary development in BSL. Further research is needed to
      investigate the relationship between vocabulary acquisition in native and non
      native signers.

PMID- 19843317
TI  - Analysis of interactions among the CLAVATA3 receptors reveals a direct
      interaction between CLAVATA2 and CORYNE in Arabidopsis.
AB  - In Arabidopsis, CORYNE (CRN), a new member of the receptor kinase family, was
      recently isolated as a key player involved in the CLAVATA3 (CLV3) signaling
      pathway, thereby playing an important role in regulating the development of shoot
      and root apical meristems. However, the precise relationships among CLAVATA1
      (CLV1), CLAVATA2 (CLV2), and CRN receptors remain unclear. Here, we demonstrate
      the subcellular localization of CRN and analyze the interactions among CLV1,
      CLV2, and CRN using firefly luciferase complementation imaging (LCI) assays in
      both Arabidopsis mesophyll protoplasts and Nicotiana benthamiana leaves.
      Fluorescence targeting showed that CRN was localized to the plasma membrane. The
      LCI assays coupled with co-immunoprecipitation assays demonstrated that CLV2 can
      directly interact with CRN in the absence of CLV3. Additional LCI assays showed
      that CLV1 did not interact with CLV2, but can interact weakly with CRN. We also
      found that CLV1 can interact with CLV2-CRN heterodimers, implying that these
      three proteins may form a complex. Moreover, CRN, rather than CLV1 and CLV2, was
      able to form homodimers without CLV3 stimulation. Taken together, our results add
      direct evidence to the newly proposed two-parallel receptor pathways model and
      therefore provide new insights into the CLV3 signaling pathway.

PMID- 19843319
TI  - Advancing early detection of autism spectrum disorder by applying an integrated
      two-stage screening approach.
AB  - BACKGROUND: Few field trials exist on the impact of implementing guidelines for
      the early detection of autism spectrum disorders (ASD). The aims of the present
      study were to develop and evaluate a clinically relevant integrated early
      detection programme based on the two-stage screening approach of Filipek et al.
      (1999), and to expand the evidence base for this approach. METHODS: The
      integrated early detection programme encompassed: 1) training relevant
      professionals to recognise early signs of autism and to use the Early Screening
      of Autistic Traits Questionnaire (ESAT; Dietz, Swinkels et al., 2006; Swinkels,
      van Daalen, van Engeland, & Buitelaar, 2006), 2) using a specific referral
      protocol, and 3) building a multidisciplinary diagnostic team. The programme was
      evaluated in a controlled study involving children in two regions (N = 2793,
      range 0-11 years). The main outcome variables were a difference in mean age at
      ASD diagnosis and a difference in the proportion of children diagnosed before 36
      months. RESULTS: ASD was diagnosed 21 months (95% CI 9.6, 32.4) earlier in the
      experimental region than in the control region during the follow-up period, with
      the mean age at ASD diagnosis decreasing by 19.5 months (95% CI 10.5, 28.5) from
      baseline in the experimental region. Children from the experimental region were
      9.4 times (95% CI 2.1, 41.3) more likely than children from the control region to
      be diagnosed before age 36 months after correction for baseline measurements.
      Most of these early diagnosed children had narrowly defined autism with mental
      retardation. CONCLUSIONS: The integrated early detection programme appears to be
      clinically relevant and led to the earlier detection of ASD, mainly in children
      with a low IQ.

PMID- 19843320
TI  - Glycogenome expression dynamics during mouse C2C12 myoblast differentiation
      suggests a sequential reorganization of membrane glycoconjugates.
AB  - BACKGROUND: Several global transcriptomic and proteomic approaches have been
      applied in order to obtain new molecular insights on skeletal myogenesis, but
      none has generated any specific data on glycogenome expression, and thus on the
      role of glycan structures in this process, despite the involvement of
      glycoconjugates in various biological events including differentiation and
      development. In the present study, a quantitative real-time RT-PCR technology was
      used to profile the dynamic expression of 375 glycogenes during the
      differentiation of C2C12 myoblasts into myotubes. RESULTS: Of the 276 genes
      expressed, 95 exhibited altered mRNA expression when C2C12 cells differentiated
      and 37 displayed more than 4-fold up- or down-regulations. Principal Component
      Analysis and Hierarchical Component Analysis of the expression dynamics
      identified three groups of coordinately and sequentially regulated genes. The
      first group included 12 down-regulated genes, the second group four genes with an
      expression peak at 24 h of differentiation, and the last 21 up-regulated genes.
      These genes mainly encode cell adhesion molecules and key enzymes involved in the
      biosynthesis of glycosaminoglycans and glycolipids (neolactoseries, lactoseries
      and ganglioseries), providing a clearer indication of how the plasma membrane and
      extracellular matrix may be modified prior to cell fusion. In particular, an
      increase in the quantity of ganglioside GM3 at the cell surface of myoblasts is
      suggestive of its potential role during the initial steps of myogenic
      differentiation. CONCLUSION: For the first time, these results provide a broad
      description of the expression dynamics of glycogenes during C2C12
      differentiation. Among the 37 highly deregulated glycogenes, 29 had never been
      associated with myogenesis. Their biological functions suggest new roles for
      glycans in skeletal myogenesis.

PMID- 19843321
TI  - Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese
      subjects: a pilot, dose finding study.
AB  - BACKGROUND: The ability to reduce inflammation in overweight and obese
      individuals may be valuable in preventing the progression to metabolic syndrome
      with associated risks for heart disease and diabetes. The purpose of this study
      was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice
      blend on indicators of inflammation and antioxidant levels in obese patients with
      elevated C-reactive protein (CRP) levels. METHODS: The study was an 8 week
      randomized, double-blind, placebo-controlled study with a pre-study 2 week
      washout period. The study included four groups including placebo and three
      difference doses of the test product, XanGo Juice: 3, 6 or 9 oz twice daily. The
      primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary
      outcome measures included other biochemical indicators of inflammation,
      anthropomorphic measures and a safety evaluation. RESULTS: One hundred twenty two
      (122) persons were screened for the study, 44 were randomized and 40 completed
      the study. HS-CRP measurements dropped after 8 weeks treatment compared to
      baseline in all 3 dose groups and increased in the placebo group. The changes
      from baseline were not significant but the comparison of change from baseline was
      significant for the 18 oz group when compared to placebo (p = 0.02). Other
      markers of inflammation (inflammatory cytokines) and a marker for lipid
      peroxidation (F2 isoprostane) did not show any significant differences when
      compared with placebo. There was a trend towards a decrease in BMI in the juice
      groups. There were no side effects reported in any of the groups and none of the
      laboratory or EKG safety assessments indicated clinically significant changes for
      any subject. CONCLUSION: In this pilot, dose-finding study, a proprietary
      mangosteen juice blend (XanGo Juice) reduced CRP levels (increased change from
      baseline) compared to placebo for those taking the highest dose of 18 oz per day.
      Further studies with a larger population are required to confirm and further
      define the benefits of this juice. The juice was administered safely. TRIAL
      REGISTRATION: ISRCTN9300027.

PMID- 19843322
TI  - An e-learning application on electrochemotherapy.
AB  - BACKGROUND: Electrochemotherapy is an effective approach in local tumour
      treatment employing locally applied high-voltage electric pulses in combination
      with chemotherapeutic drugs. In planning and performing electrochemotherapy a
      multidisciplinary expertise is required and collaboration, knowledge and
      experience exchange among the experts from different scientific fields such as
      medicine, biology and biomedical engineering is needed. The objective of this
      study was to develop an e-learning application in order to provide the
      educational content on electrochemotherapy and its underlying principles and to
      support collaboration, knowledge and experience exchange among the experts
      involved in the research and clinics. METHODS: The educational content on
      electrochemotherapy and cell and tissue electroporation was based on previously
      published studies from molecular dynamics, lipid bilayers, single cell level and
      simplified tissue models to complex biological tissues and research and clinical
      results of electrochemotherapy treatment. We used computer graphics such as model
      based visualization (i.e. 3D numerical modelling using finite element method) and
      3D computer animations and graphical illustrations to facilitate the
      representation of complex biological and physical aspects in electrochemotherapy.
      The e-learning application is integrated into an interactive e-learning
      environment developed at our institution, enabling collaboration and knowledge
      exchange among the users. We evaluated the designed e-learning application at the
      International Scientific workshop and postgraduate course (Electroporation Based
      Technologies and Treatments). The evaluation was carried out by testing the
      pedagogical efficiency of the presented educational content and by performing the
      usability study of the application. RESULTS: The e-learning content presents
      three different levels of knowledge on cell and tissue electroporation. In the
      first part of the e-learning application we explain basic principles of
      electroporation process. The second part provides educational content about
      importance of modelling and visualization of local electric field in
      electroporation-based treatments. In the third part we developed an interactive
      module for visualization of local electric field distribution in 3D tissue models
      of cutaneous tumors for different parameters such as voltage applied, distance
      between electrodes, electrode dimension and shape, tissue geometry and electric
      conductivity. The pedagogical efficiency assessment showed that the participants
      improved their level of knowledge. The results of usability evaluation revealed
      that participants found the application simple to learn, use and navigate. The
      participants also found the information provided by the application easy to
      understand. CONCLUSION: The e-learning application we present in this article
      provides educational material on electrochemotherapy and its underlying
      principles such as cell and tissue electroporation. The e-learning application is
      developed to provide an interactive educational content in order to simulate the
      "hands-on" learning approach about the parameters being important for successful
      therapy. The e-learning application together with the interactive e-learning
      environment is available to the users to provide collaborative and flexible
      learning in order to facilitate knowledge exchange among the experts from
      different scientific fields that are involved in electrochemotherapy. The modular
      structure of the application allows for upgrade with new educational content
      collected from the clinics and research, and can be easily adapted to serve as a
      collaborative e-learning tool also in other electroporation-based treatments such
      as gene electrotransfer, gene vaccination, irreversible tissue ablation and
      transdermal gene and drug delivery. The presented e-learning application provides
      an easy and rapid approach for information, knowledge and experience exchange
      among the experts from different scientific fields, which can facilitate
      development and optimisation of electroporation-based treatments.

PMID- 19843323
TI  - Electrophysiological evidence for an early processing of human voices.
AB  - BACKGROUND: Previous electrophysiological studies have identified a "voice
      specific response" (VSR) peaking around 320 ms after stimulus onset, a latency
      markedly longer than the 70 ms needed to discriminate living from non-living
      sound sources and the 150 ms to 200 ms needed for the processing of voice
      paralinguistic qualities. In the present study, we investigated whether an early
      electrophysiological difference between voice and non-voice stimuli could be
      observed. RESULTS: ERPs were recorded from 32 healthy volunteers who listened to
      200 ms long stimuli from three sound categories - voices, bird songs and
      environmental sounds - whilst performing a pure-tone detection task. ERP analyses
      revealed voice/non-voice amplitude differences emerging as early as 164 ms post
      stimulus onset and peaking around 200 ms on fronto-temporal (positivity) and
      occipital (negativity) electrodes. CONCLUSION: Our electrophysiological results
      suggest a rapid brain discrimination of sounds of voice, termed the "fronto
      temporal positivity to voices" (FTPV), at latencies comparable to the well-known
      face-preferential N170.

PMID- 19843324
TI  - The incidence and risk of developing a second primary esophageal cancer in
      patients with oral and pharyngeal carcinoma: a population-based study in Taiwan
      over a 25 year period.
AB  - BACKGROUND: The incidence of oral and pharyngeal (including oral cavity,
      oropharynx and hypopharynx) carcinoma increases rapidly in Asia and South Pacific
      because of betel quid chewing. Thus far, large-scale epidemiological studies are
      not available yet to stratify these patients by their risks of developing a
      second primary cancer in the digestive tract including esophagus, stomach, colon,
      and rectum. METHODS: A population-based study was conducted using the database
      from the Taiwan National Cancer Registry for the period 1979-2003. We quantified
      standardized incidence ratios (SIRs) and cumulative incidence of second primary
      cancers among 33,787 patients with initial diagnoses of oral and pharyngeal
      carcinoma. RESULTS: Among these four digestive tract organs, the esophagus was
      the only site of second cancer with excess risk in patients with oral and
      pharyngeal carcinoma. The incidence and risk of developing a second primary
      esophageal cancer differed by the site of the primary index tumor, most
      frequently seen in hypopharyngeal cancer (71/4,218 = 1.68%, SIR = 22.76, 95% CI
      17.77-28.70), followed by oropharyngeal cancer (30/3,403 = 0.88%, SIR = 14.29,
      95% CI 9.64-20.39) and the least in oral cavity cancer (99/26,166 = 0.38%, SIR =
      5.57, 95% CI 4.53-6.78). In addition, the risk was extraordinarily high for
      patients with a follow-up interval <or= 1 year and those with first primary
      cancer diagnosed at age <or=50. These patients may justify more close
      surveillance. CONCLUSION: The present study represents the first population-based
      study in Asia attempting to stratify the patients of oral and pharyngeal
      carcinoma by their risk of developing a second esophageal cancer. It helps
      identify patients at high risk and tailor the application of intense follow-up
      surveillance to the estimated risk in each individual case.

PMID- 19843325
TI  - Motorcyclists' reactions to safety helmet law: a qualitative study.
AB  - BACKGROUND: Extensive body of the literature reveals that proper use of helmets
      is an effective way to reduce the severity of injuries and fatalities among
      motorcyclists. However, many motorcyclists do not use safety helmet properly.
      This study aimed to empirically explore reactions of motorcyclists to the safety
      helmet laws, in Iran. METHODS: Qualitative data were collected via four focus
      groups and 11 in-depth interviews. Participants were 28 male motorcyclists who
      never used a safety helmet during rides, and 4 male police officers. All
      transcripts, codes and categories were read for several times to exhaust
      identifiable major themes. During this process data were reduced from text to
      codes and themes. RESULTS: Five major themes emerged from the data analyses,
      including themes related to the following: (1) circumventing or dodging police
      officers; (2) simulating a helmet wearing behavior; (3) accepting the probability
      of receiving a ticket; (4) taking advantage of the police neglect and
      carelessness; and (5) using a cheap or convenient helmet. CONCLUSION: Our
      findings suggest certain levels of reckless driving among the participating
      motorcyclists in this study. They also point to a system of law enforcement that
      operates haphazardly and fails to consistently penalize those who deviate from
      it. Further studies are needed to investigate how "risks" are perceived and
      relate to "reactions", and how a 'culture of masculinity' may encourage risk
      tolerance and a disposition toward lawlessness and carelessness among male
      motorcyclists. Also, there is a need for the development and implementation of
      multidimensional interventions that would offer socio-culturally sensitive
      educational and motivational messages to the motorcyclists and the in-service
      traffic-enforcement officers in Iran.

PMID- 19843327
TI  - Retraction: estimation of progression of multi-state chronic disease using the
      Markov model and prevalence pool concept.
AB  - This article has been retracted because the Editors are unable to ensure the
      scientific veracity of the findings or the ethical conduct of the authors despite
      an extensive investigation.

PMID- 19843326
TI  - Genetic variation in insulin-like growth factor signaling genes and breast cancer
      risk among BRCA1 and BRCA2 carriers.
AB  - INTRODUCTION: Women who carry mutations in BRCA1 and BRCA2 have a substantially
      increased risk of developing breast cancer as compared with the general
      population. However, risk estimates range from 20 to 80%, suggesting the presence
      of genetic and/or environmental risk modifiers. Based on extensive in vivo and in
      vitro studies, one important pathway for breast cancer pathogenesis may be the
      insulin-like growth factor (IGF) signaling pathway, which regulates both cellular
      proliferation and apoptosis. BRCA1 has been shown to directly interact with IGF
      signaling such that variants in this pathway may modify risk of cancer in women
      carrying BRCA mutations. In this study, we investigate the association of
      variants in genes involved in IGF signaling and risk of breast cancer in women
      who carry deleterious BRCA1 and BRCA2 mutations. METHODS: A cohort of 1,665
      adult, female mutation carriers, including 1,122 BRCA1 carriers (433 cases) and
      543 BRCA2 carriers (238 cases) were genotyped for SNPs in IGF1, IGF1 receptor
      (IGF1R), IGF1 binding protein (IGFBP1, IGFBP2, IGFBP5), and IGF receptor
      substrate 1 (IRS1). Cox proportional hazards regression was used to model time
      from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately.
      For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic
      model was assumed; and for single SNP analyses, no additivity assumptions were
      made. RESULTS: Among BRCA1 carriers, significant associations were found between
      risk of breast cancer and LD blocks in IGF1R (global P = 0.011 for LD block 2 and
      global P = 0.012 for LD block 11). Among BRCA2 carriers, an LD block in IGFBP2
      (global P = 0.0145) was found to be associated with the time to breast cancer
      diagnosis. No significant LD block associations were found for the other
      investigated genes among BRCA1 and BRCA2 carriers. CONCLUSIONS: This is the first
      study to investigate the role of genetic variation in IGF signaling and breast
      cancer risk in women carrying deleterious mutations in BRCA1 and BRCA2. We
      identified significant associations in variants in IGF1R and IRS1 in BRCA1
      carriers and in IGFBP2 in BRCA2 carriers. Although there is known to be
      interaction of BRCA1 and IGF signaling, further replication and identification of
      causal mechanisms are needed to better understand these associations.

PMID- 19843328
TI  - An EIAV field isolate reveals much higher levels of subtype variability than
      currently reported for the equine lentivirus family.
AB  - BACKGROUND: Equine infectious anemia virus (EIAV), a lentivirus that infects
      horses, has been utilized as an animal model for the study of HIV. Furthermore,
      the disease associated with the equine lentivirus poses a significant challenge
      to veterinary medicine around the world. As with all lentiviruses, EIAV has been
      shown to have a high propensity for genomic sequence and antigenic variation,
      especially in its envelope (Env) proteins. Recent studies have demonstrated Env
      variation to be a major determinant of vaccine efficacy, emphasizing the
      importance of defining natural variation among field isolates of EIAV. To date,
      however, published EIAV sequences have been reported only for cell-adapted
      strains of virus, predominantly derived from a single primary virus isolate,
      EIAVWyoming (EIAVWY). RESULTS: We present here the first characterization of the
      Env protein of a natural primary isolate from Pennsylvania (EIAVPA) since the
      widely utilized and referenced EIAVWY strain. The data demonstrated that the
      level of EIAVPA Env amino acid sequence variation, approximately 40% as compared
      to EIAVWY, is much greater than current perceptions or published reports of
      natural EIAV variation between field isolates. This variation did not appear to
      give rise to changes in the predicted secondary structure of the proteins. While
      the EIAVPA Env was serologically cross reactive with the Env proteins of the cell
      adapted reference strain, EIAVPV (derivative of EIAVWY), the two variant Envs
      were shown to lack any cross neutralization by immune serum from horses infected
      with the respective virus strains. CONCLUSION: Taking into account the
      significance of serum neutralization to universal vaccine efficacy, these
      findings are crucial considerations towards successful EIAV vaccine development
      and the potential inclusion of field isolate Envs in vaccine candidates.

PMID- 19843329
TI  - Are algal genes in nonphotosynthetic protists evidence of historical plastid
      endosymbioses?
AB  - BACKGROUND: How photosynthetic organelles, or plastids, were acquired by diverse
      eukaryotes is among the most hotly debated topics in broad scale eukaryotic
      evolution. The history of plastid endosymbioses commonly is interpreted under the
      "chromalveolate" hypothesis, which requires numerous plastid losses from certain
      heterotrophic groups that now are entirely aplastidic. In this context,
      discoveries of putatively algal genes in plastid-lacking protists have been cited
      as evidence of gene transfer from a photosynthetic endosymbiont that subsequently
      was lost completely. Here we examine this evidence, as it pertains to the
      chromalveolate hypothesis, through genome-level statistical analyses of
      similarity scores from queries with two diatoms, Phaeodactylum tricornutum and
      Thalassiosira pseudonana, and two aplastidic sister taxa, Phytophthora ramorum
      and P. sojae. RESULTS: Contingency tests of specific predictions of the
      chromalveolate model find no evidence for an unusual red algal contribution to
      Phytophthora genomes, nor that putative cyanobacterial sequences that are present
      entered these genomes through a red algal endosymbiosis. Examination of genes
      unrelated to plastid function provide extraordinarily significant support for
      both of these predictions in diatoms, the control group where a red endosymbiosis
      is known to have occurred, but none of that support is present in genes
      specifically conserved between diatoms and oomycetes. In addition, we uncovered a
      strong association between overall sequence similarities among taxa and relative
      sizes of genomic data sets in numbers of genes. CONCLUSION: Signal from "algal"
      genes in oomycete genomes is inconsistent with the chromalveolate hypothesis, and
      better explained by alternative models of sequence and genome evolution. Combined
      with the numerous sources of intragenomic phylogenetic conflict characterized
      previously, our results underscore the potential to be mislead by a posteriori
      interpretations of variable phylogenetic signals contained in complex genome
      level data. They argue strongly for explicit testing of the different a priori
      assumptions inherent in competing evolutionary hypotheses.

PMID- 19843330
TI  - Blood pressure lowering treatment for preventing stroke recurrence: a systematic
      review and meta-analysis.
AB  - BACKGROUND: While hypertension is a leading risk factor for an initial stroke,
      the role of blood pressure lowering to prevent subsequent stroke is less clear.
      The results of recent large clinical trials investigating effects of
      antihypertensive agents in patients with a history of stroke have not shown a
      significant benefit; findings that are at odds with previous data. Our meta
      analysis systematically evaluates the available, relevant trials to examine the
      role of antihypertensive drugs in preventing recurrent stroke. METHODS: MEDLINE,
      CENTRAL, and ClinicalTrials.gov were systematically searched and bibliographies
      from key reports were examined. All randomized, placebo-controlled trials that
      tested blood pressure lowering agents in patients with stroke or transient
      ischemic attack were identified. The results from these trials were combined and
      meta-analyses were performed. RESULTS: Ten studies were found to contain relevant
      endpoints and presented data allowing meta-analysis. Agents that lowered blood
      pressure reduced recurrent stroke (OR 0.71, 95% CI 0.59-0.86, P = 0.0004) and
      cardiovascular events (OR 0.69, 95% CI 0.57-0.85, P = 0.0004) in patients with a
      previous stroke or TIA. These agents did not affect the rate of myocardial
      infarction (OR 0.86, 95% CI 0.73-1.01, P = 0.07) or all-cause mortality (OR 0.95,
      95% CI 0.83-1.07, P = 0.39) in this patient population. CONCLUSION: Despite
      recent large trials showing no significant effect, in patients that have
      experienced a TIA or stroke, blood pressure lowering agents reduced the
      occurrence of subsequent stroke and cardiovascular events. The rate of myocardial
      infarction and all-cause mortality was unchanged.

PMID- 19843331
TI  - A scan statistic for continuous data based on the normal probability model.
AB  - Temporal, spatial and space-time scan statistics are commonly used to detect and
      evaluate the statistical significance of temporal and/or geographical disease
      clusters, without any prior assumptions on the location, time period or size of
      those clusters. Scan statistics are mostly used for count data, such as disease
      incidence or mortality. Sometimes there is an interest in looking for clusters
      with respect to a continuous variable, such as lead levels in children or low
      birth weight. For such continuous data, we present a scan statistic where the
      likelihood is calculated using the the normal probability model. It may also be
      used for other distributions, while still maintaining the correct alpha level. In
      an application of the new method, we look for geographical clusters of low birth
      weight in New York City.

PMID- 19843332
TI  - Managing insecticide resistance in malaria vectors by combining carbamate-treated
      plastic wall sheeting and pyrethroid-treated bed nets.
AB  - BACKGROUND: Pyrethroid resistance is now widespread in Anopheles gambiae, the
      major vector for malaria in sub-Saharan Africa. This resistance may compromise
      malaria vector control strategies that are currently in use in endemic areas. In
      this context, a new tool for management of resistant mosquitoes based on the
      combination of a pyrethroid-treated bed net and carbamate-treated plastic
      sheeting was developed. METHODS: In the laboratory, the insecticidal activity and
      wash resistance of four carbamate-treated materials: a cotton/polyester blend, a
      polyvinyl chloride tarpaulin, a cotton/polyester blend covered on one side with
      polyurethane, and a mesh of polypropylene fibres was tested. These materials were
      treated with bendiocarb at 100 mg/m(2) and 200 mg/m(2) with and without a binding
      resin to find the best combination for field studies. Secondly, experimental hut
      trials were performed in southern Benin to test the efficacy of the combined use
      of a pyrethroid-treated bed net and the carbamate-treated material that was the
      most wash-resistant against wild populations of pyrethroid-resistant An. gambiae
      and Culex quinquefasciatus. RESULTS: Material made of polypropylene mesh (PPW)
      provided the best wash resistance (up to 10 washes), regardless of the
      insecticide dose, the type of washing, or the presence or absence of the binding
      resin. The experimental hut trial showed that the combination of carbamate
      treated PPW and a pyrethroid-treated bed net was extremely effective in terms of
      mortality and inhibition of blood feeding of pyrethroid-resistant An. gambiae.
      This efficacy was found to be proportional to the total surface of the walls.
      This combination showed a moderate effect against wild populations of Cx.
      quinquefasciatus, which were strongly resistant to pyrethroid. CONCLUSION: These
      preliminary results should be confirmed, including evaluation of entomological,
      parasitological, and clinical parameters. Selective pressure on resistance
      mechanisms within the vector population, effects on other pest insects, and the
      acceptability of this management strategy in the community also need to be
      evaluated.

PMID- 19843333
TI  - Real time in vitro studies of doxorubicin release from PHEMA nanoparticles.
AB  - BACKGROUND: Many anticancer agents have poor water solubility and therefore the
      development of novel delivery systems for such molecules has received significant
      attention. Nanocarriers show great potential in delivering therapeutic agents
      into the targeted organs or cells and have recently emerged as a promising
      approach to cancer treatments. The aim of this study was to prepare and use poly
      2-hydroxyethyl methacrylate (PHEMA) nanoparticles for the controlled release of
      the anticancer drug doxorubicin. RESULTS: PHEMA nanoparticles have been
      synthesized and characterized using FTIR and scanning electron microscopy (SEM),
      particle size analysis and surface charge measurements. We also studied the
      effects of various parameters such as percent loading of drugs, chemical
      architecture of the nanocarriers, pH, temperature and nature of the release media
      on the release profiles of the drug. The chemical stability of doxorubicin in PBS
      was assessed at a range of pH. CONCLUSION: Suspension polymerization of 2
      hydroxyethyl methacrylate (HEMA) results in the formation of swellable
      nanoparticles of defined composition. PHEMA nanoparticles can potentially be used
      for the controlled release of the anticancer drug doxorubicin.

PMID- 19843334
TI  - Demodex gatoi-associated contagious pruritic dermatosis in cats--a report from
      six households in Finland.
AB  - BACKGROUND: Demodex gatoi is unique among demodectic mites. It possesses a
      distinct stubby appearance, and, instead of residing in the hair follicles, it
      dwells in the keratin layer of the epidermis, causing a pruritic and contagious
      skin disease in cats. Little is known of the occurrence of D. gatoi in Europe or
      control of D. gatoi infestation. CASE PRESENTATION: We describe D. gatoi in 10
      cats, including five Cornish Rex, two Burmese, one Exotic, one Persian and one
      Siamese, living in six multi-cat households in different locations in Finland
      containing 21 cats in total. Intense pruritus was the main clinical sign.
      Scaling, broken hairs, alopecia and self-inflicted excoriations were also
      observed. Diagnosis was based on finding typical short-bodied demodectic mites in
      skin scrapings, skin biopsies or on tape strips. Other pruritic skin diseases,
      such as allergies and dermatophytoses, were ruled out. In one household, despite
      finding several mites on one cat, all six cats of the household remained
      symptomless. Amitraz used weekly at a concentration of 125-250 ppm for 2-3
      months, proved successful in three households, 2% lime sulphur weekly dips
      applied for six weeks in one household and peroral ivermectin (1 mg every other
      day for 10 weeks) in one household. Previous trials in four households with
      imidacloprid-moxidectin, selamectin or injected ivermectin given once or twice a
      month appeared ineffective. CONCLUSION: D. gatoi-associated dermatitis is an
      emerging contagious skin disease in cats in Finland. Although pruritus is common,
      some cats may harbour the mites without clinical signs. In addition, due to
      translucency of the mites and fastidious feline grooming habits, the diagnosis
      may be challenging. An effective and convenient way to treat D. gatoi
      infestations has yet to emerge.

PMID- 19843335
TI  - Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae,
      Fabaceae and Poaceae.
AB  - BACKGROUND: Accurate computational identification of cis-regulatory motifs is
      difficult, particularly in eukaryotic promoters, which typically contain multiple
      short and degenerate DNA sequences bound by several interacting factors.
      Enrichment in combinations of rare motifs in the promoter sequence of
      functionally or evolutionarily related genes among several species is an
      indicator of conserved transcriptional regulatory mechanisms. This provides a
      basis for the computational identification of cis-regulatory motifs. RESULTS: We
      have used a discriminative seeding DNA motif discovery algorithm for an in-depth
      analysis of 54 seed storage protein (SSP) gene promoters from three plant
      families, namely Brassicaceae (mustards), Fabaceae (legumes) and Poaceae
      (grasses) using backgrounds based on complete sets of promoters from a
      representative species in each family, namely Arabidopsis (Arabidopsis thaliana
      (L.) Heynh.), soybean (Glycine max (L.) Merr.) and rice (Oryza sativa L.)
      respectively. We have identified three conserved motifs (two RY-like and one ACGT
      like) in Brassicaceae and Fabaceae SSP gene promoters that are similar to
      experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP
      gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like
      motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4
      like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the
      presence of a variant of the TATA-box is found in the SSP gene promoters from the
      three plant families. Motifs discovered in SSP gene promoters were used to score
      whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest
      scoring promoters are associated with genes coding for different subunits or
      precursors of seed storage proteins. CONCLUSION: Seed storage protein gene
      promoter motifs are conserved in diverse species, and different plant families
      are characterized by a distinct combination of conserved motifs. The majority of
      discovered motifs match experimentally characterized cis-regulatory elements.
      These results provide a good starting point for further experimental analysis of
      plant seed-specific promoters and our methodology can be used to unravel more
      transcriptional regulatory mechanisms in plants and other eukaryotes.

PMID- 19843336
TI  - Characterization of global microRNA expression reveals oncogenic potential of miR
      145 in metastatic colorectal cancer.
AB  - BACKGROUND: MicroRNAs (MiRNAs) are short non-coding RNAs that control protein
      expression through various mechanisms. Their altered expression has been shown to
      be associated with various cancers. The aim of this study was to profile miRNA
      expression in colorectal cancer (CRC) and to analyze the function of specific
      miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA
      expression profile in eight CRC cell line models, 45 human CRC samples of
      different stages, and four matched normal colon tissue samples. SW620 CRC cells
      were stably transduced with miR-143 or miR-145 expression vectors and analyzed in
      vitro for cell proliferation, cell differentiation and anchorage-independent
      growth. Signalling pathways associated with differentially expressed miRNAs were
      identified using a gene set enrichment analysis. RESULTS: The expression analysis
      of clinical CRC samples identified 37 miRNAs that were differentially expressed
      between CRC and normal tissue. Furthermore, several of these miRNAs were
      associated with CRC tumor progression including loss of miR-133a and gain of miR
      224. We identified 11 common miRNAs that were differentially expressed between
      normal colon and CRC in both the cell line models and clinical samples. In vitro
      functional studies indicated that miR-143 and miR-145 appear to function in
      opposing manners to either inhibit or augment cell proliferation in a metastatic
      CRC model. The pathways targeted by miR-143 and miR-145 showed no significant
      overlap. Furthermore, gene expression analysis of metastatic versus non
      metastatic isogenic cell lines indicated that miR-145 targets involved in cell
      cycle and neuregulin pathways were significantly down-regulated in the metastatic
      context. CONCLUSION: MiRNAs showing altered expression at different stages of CRC
      could be targets for CRC therapies and be further developed as potential
      diagnostic and prognostic analytes. The identified biological processes and
      signalling pathways collectively targeted by co-expressed miRNAs in CRC provide a
      basis for understanding the functional role of miRNAs in cancer.

PMID- 19843337
TI  - Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline
      susceptibility factors for colorectal cancer.
AB  - BACKGROUND: Variation in genes involved in the innate immune response may play a
      role in the predisposition to colorectal cancer (CRC). Several polymorphisms of
      the CARD15 gene (caspase activating recruitment domain, member 15) have been
      reported to be associated with an increased susceptibility to Crohn disease.
      Since the CARD15 gene product and other CARD proteins function in innate
      immunity, we investigated the impact of germline variation at the CARD4, CARD8
      and CARD15 loci on the risk for sporadic CRC, using a large patient sample from
      Northern Germany. METHODS: A total of 1044 patients who had been operated with
      sporadic colorectal carcinoma (median age at diagnosis: 59 years) were recruited
      and compared to 724 sex-matched, population-based control individuals (median
      age: 68 years). Genetic investigation was carried out following both a coding SNP
      and haplotype tagging approach. Subgroup analyses for N = 143 patients with early
      manifestation of CRC (<or=50 age at diagnosis) were performed for all CARD loci
      and subgroup analyses for diverse age strata were carried out for CARD15
      mutations R702W, G908R and L1007fs. In addition, all SNPs were tested for
      association with disease presentation and family history of CRC. RESULTS: No
      significant differences were observed between the patient and control allelic or
      haplotypic spectra of the three genes under study for the total cohort (N = 1044
      patients). None of the analysed SNPs was significantly associated with either
      tumour location or yielded significant association in the familial or non
      familial CRC patient subgroups. However, in a patient subgroup (<or=45 age at
      diagnosis) with early disease manifestation the mutant allele of CARD15 R702W was
      found to be significantly associated with disease susceptibility (9.7% in cases
      vs 4.6% in controls; P(allelic) = 0.008, P(genotypic) = 0.0008, OR(allelic) =
      2.22 (1.21-4.05) OR(ressessive) = 21.9 (1.96-245.4). CONCLUSION: Variation in the
      innate immunity genes CARD4, CARD8 and CARD15 is unlikely to play a major role in
      the susceptibility to CRC in the German population. But, we report a significant
      disease contribution of CARD15 for CRC patients with very early disease
      manifestation, mainly driven by variant R702W.

PMID- 19843338
TI  - Low and moderate-fat plant sterol fortified soymilk in modulation of plasma
      lipids and cholesterol kinetics in subjects with normal to high cholesterol
      concentrations: report on two randomized crossover studies.
AB  - BACKGROUND: Although consumption of various plant sterol (PS)-enriched beverages
      is effective in lowering plasma cholesterol, the lipid-lowering potential of PS
      in a soymilk format has not been investigated thoroughly. Therefore, to evaluate
      the efficacy of PS-enriched soy beverages on plasma lipids and cholesterol
      kinetics, we conducted two separate 28 d dietary controlled cross-over studies.
      In study 1, the cholesterol-lowering efficacy of a low-fat (2 g/serving) PS
      enriched soy beverage was examined in 33 normal cholesterolemic subjects in
      comparison with 1% dairy milk. In study 2, we investigated the efficacy of a
      moderate-fat (3.5 g/serving) PS-enriched soy beverage on plasma cholesterol
      concentrations and cholesterol kinetic responses in 23 hypercholesterolemic
      subjects compared with 1% dairy milk. Both the low and moderate-fat PS-enriched
      soymilk varieties provided 1.95 g PS/d. Endpoint plasma variables were analyzed
      by repeated-measures ANOVA using baseline values as covariates for plasma lipid
      measurements. RESULTS: In comparison with the 1% dairy milk control, the low-fat
      soy beverage reduced (P < 0.05) total and LDL-cholesterol by 10 and 13%,
      respectively. Consumption of the moderate-fat PS-enriched soy beverage reduced (P
      < 0.05) plasma total and LDL-cholesterol by 12 and 15% respectively. Fasting
      triglycerides were reduced by 9.4% following consumption of the moderate-fat soy
      beverage in comparison with the 1% dairy milk. Both low and moderate-fat PS
      enriched soy varieties reduced (P < 0.05) LDL:HDL and TC:HDL ratios compared with
      the 1% dairy milk control. Consumption of the moderate-fat PS-enriched soymilk
      reduced (P < 0.05) cholesterol absorption by 27%, but did not alter cholesterol
      synthesis in comparison with 1% dairy milk. CONCLUSION: We conclude that,
      compared to 1% dairy milk, consumption of low and moderate-fat PS-enriched soy
      beverages represents an effective dietary strategy to reduce circulating lipid
      concentrations in normal to hypercholesterolemic individuals by reducing
      intestinal cholesterol absorption. TRIAL REGISTRATION (CLINICALTRIALS.GOV):
      NCT00923403 (Study 1), NCT00924391 (Study 2).

PMID- 19843339
TI  - The theory of discovering rare variants via DNA sequencing.
AB  - BACKGROUND: Rare population variants are known to have important biomedical
      implications, but their systematic discovery has only recently been enabled by
      advances in DNA sequencing. The design process of a discovery project remains
      formidable, being limited to ad hoc mixtures of extensive computer simulation and
      pilot sequencing. Here, the task is examined from a general mathematical
      perspective. RESULTS: We pose and solve the population sequencing design problem
      and subsequently apply standard optimization techniques that maximize the
      discovery probability. Emphasis is placed on cases whose discovery thresholds
      place them within reach of current technologies. We find that parameter values
      characteristic of rare-variant projects lead to a general, yet remarkably simple
      set of optimization rules. Specifically, optimal processing occurs at constant
      values of the per-sample redundancy, refuting current notions that sample size
      should be selected outright. Optimal project-wide redundancy and sample size are
      then shown to be inversely proportional to the desired variant frequency. A
      second family of constants governs these relationships, permitting one to
      immediately establish the most efficient settings for a given set of discovery
      conditions. Our results largely concur with the empirical design of the Thousand
      Genomes Project, though they furnish some additional refinement. CONCLUSION: The
      optimization principles reported here dramatically simplify the design process
      and should be broadly useful as rare-variant projects become both more important
      and routine in the future.

PMID- 19843340
TI  - Effectiveness of focused structural massage and relaxation massage for chronic
      low back pain: protocol for a randomized controlled trial.
AB  - BACKGROUND: Chronic back pain is a major public health problem and the primary
      reason patients seek massage treatment. Despite the growing use of massage for
      chronic low back pain, there have been few studies of its effectiveness. This
      trial will be the first evaluation of the effectiveness of relaxation massage for
      chronic back pain and the first large trial of a focused structural form of
      massage for this condition. METHODS AND DESIGN: A total of 399 participants (133
      in each of three arms) between the ages of 20 and 65 years of age who have low
      back pain lasting at least 3 months will be recruited from an integrated health
      care delivery system. They will be randomized to one of two types of massage
      ("focused structural massage" or "relaxation massage"), or continued usual
      medical care. Ten massage treatments will be provided over 10 weeks. The primary
      outcomes, standard measures of dysfunction and bothersomeness of low back pain,
      will be assessed at baseline and after 10, 26, and 52 weeks by telephone
      interviewers masked to treatment assignment. General health status, satisfaction
      with back care, days of back-related disability, perceived stress, and use and
      costs of healthcare services for back pain will also be measured. Outcomes across
      assigned treatment groups will be compared using generalized estimating
      equations, accounting for participant correlation and adjusted for baseline
      value, age, and sex. For both primary outcome measures, this trial will have at
      least 85% power to detect the presence of a minimal clinically significant
      difference among the three treatment groups and 91% power for pairwise
      comparisons. Secondary analyses will compare the proportions of participants in
      each group that improve by a clinically meaningful amount. CONCLUSION: Results of
      this trial will help clarify the value of two types of massage therapy for
      chronic low back pain.

PMID- 19843341
TI  - Medication management and practices in prison for people with mental health
      problems: a qualitative study.
AB  - BACKGROUND: Common mental health problems are prevalent in prison and the quality
      of prison health care provision for prisoners with mental health problems has
      been a focus of critical scrutiny. Currently, health policy aims to align and
      integrate prison health services and practices with those of the National Health
      Service (NHS). Medication management is a key aspect of treatment for patients
      with a mental health problem. The medication practices of patients and staff are
      therefore a key marker of the extent to which the health practices in prison
      settings equate with those of the NHS. The research reported here considers the
      influences on medication management during the early stages of custody and the
      impact it has on prisoners. METHODS: The study employed a qualitative design
      incorporating semi-structured interviews with 39 prisoners and 71 staff at 4
      prisons. Participant observation was carried out in key internal prison locations
      relevant to the management of vulnerable prisoners to support and inform the
      interview process. Thematic analysis of the interview data and interpretation of
      the observational field-notes were undertaken manually. Emergent themes included
      the impact that delays, changes to or the removal of medication have on prisoners
      on entry to prison, and the reasons that such events take place. RESULTS AND
      DISCUSSION: Inmates accounts suggested that psychotropic medication was found a
      key and valued form of support for people with mental health problems entering
      custody. Existing regimes of medication and the autonomy to self-medicate
      established in the community are disrupted and curtailed by the dominant
      practices and prison routines for the taking of prescribed medication. The
      continuity of mental health care is undermined by the removal or alteration of
      existing medication practice and changes on entry to prison which exacerbate
      prisoners' anxiety and sense of helplessness. Prisoners with a dual diagnosis are
      likely to be doubly vulnerable because of inconsistencies in substance withdrawal
      management. CONCLUSION: Changes to medication management which accompany entry to
      prison appear to contribute to poor relationships with prison health staff,
      disrupts established self-medication practices, discourages patients from taking
      greater responsibility for their own conditions and detrimentally affects the
      mental health of many prisoners at a time when they are most vulnerable. Such
      practices are likely to inhibit the integration and normalisation of mental
      health management protocols in prison as compared with those operating in the
      wider community and may hinder progress towards improving the standard of mental
      health care available to prisoners suffering from mental disorder.

PMID- 19843343
TI  - Clinical experience of novel interconnected porous hydroxyapatite ceramics for
      the revision of tumor prosthesis: a case report.
AB  - BACKGROUND: As for being cautious with tumor prostheses, revision of uncemented
      tumor prostheses in particular, it is necessary to remove cortical bone from the
      stem circumference with a chisel when the stem is extracted. This assures that
      bone in-growth will occur within the stem in itself. As a result, re-substitution
      of mass autogenous bone graft round a new stem is subsequently necessary. When
      rivision of uncemented tumor prosthesis of distal femur was performed, we evade
      fibula transplant by transplanting interconnected porous hydroxyapatite ceramic
      (IP-CA: Neobone) with a self bone, and reports its experience with the case that
      acquired enough strength. CASE REPORT: In this report, we present the case of a
      27-year-old female with stem breakage of tumor prosthesis and do revision surgery
      for prosthetic failure. In the case of revision surgery, autologous bone and
      Neobone were mixed, and this was transplanted to stem circumference. The
      Radiological Evaluation System of the ISOLS showed excellent results for all
      items. She can walk without using a cane or orthosis, and the score of the MSTS
      is 80%. CONCLUSION: When revision of uncemented tumor prostheses of the distal
      femur was performed, we avoided fibula graft by using Neobone with the patient's
      own bone tissue. Our experience with this case may indicate that adequate
      strength is achieved.

PMID- 19843342
TI  - Chronic kidney disease increases cardiovascular unfavourable outcomes in
      outpatients with heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) has a high morbidity and mortality.
      Chronic kidney disease (CKD) has consistently been found to be an independent
      risk factor for unfavorable cardiovascular (CV) outcomes. Early intervention on
      CKD reduces the progression of CHF, hospitalizations and mortality, yet there are
      very few studies about CKD as a risk factor in the early stages of CHF. The aims
      of our study were to assess the prevalence and the prognostic importance of CKD
      in patients with systolic CHF stages B and C. METHODS: This is a prospective
      cohort study, dealing with prognostic markers for CV endpoints in patients with
      systolic CHF (ejection fraction <or= 45%). RESULTS: CKD was defined as estimated
      glomerular filtration rate <60 mL/min/1.73 m2 and CV endpoints as death or
      hospitalization due to CHF, in 12 months follow-up. Eighty three patients were
      studied, the mean age was 62.7 +/- 12 years, and 56.6% were female. CKD was
      diagnosed in 49.4% of the patients, 33% of patients with CHF stage B and 67% in
      the stage C. Cardiovascular endpoints were observed in 26.5% of the patients.
      When the sample was stratified into stages B and C of CHF, the occurrence of CKD
      was associated with 100% and 64.7%, respectively, of unfavorable CV outcomes.
      After adjustments for all other prognostic factors at baseline, it was observed
      that the diagnosis of CKD increased in 3.6 times the possibility of CV outcomes
      (CI 95% 1.04-12.67, p = 0.04), whereas higher ejection fraction (R = 0.925, IC
      95% 0.862-0.942, p = 0.03) and serum sodium (R = 0.807, IC 95% 0.862-0.992, p =
      0.03) were protective. CONCLUSION: In this cohort of patients with CHF stages B
      and C, CKD was prevalent and independently associated with increased risk of
      hospitalization and death secondary to cardiac decompensation, especially in
      asymptomatic patients.

PMID- 19843344
TI  - KAIKObase: an integrated silkworm genome database and data mining tool.
AB  - BACKGROUND: The silkworm, Bombyx mori, is one of the most economically important
      insects in many developing countries owing to its large-scale cultivation for
      silk production. With the development of genomic and biotechnological tools, B.
      mori has also become an important bioreactor for production of various
      recombinant proteins of biomedical interest. In 2004, two genome sequencing
      projects for B. mori were reported independently by Chinese and Japanese teams;
      however, the datasets were insufficient for building long genomic scaffolds which
      are essential for unambiguous annotation of the genome. Now, both the datasets
      have been merged and assembled through a joint collaboration between the two
      groups. DESCRIPTION: Integration of the two data sets of silkworm whole-genome
      shotgun sequencing by the Japanese and Chinese groups together with newly
      obtained fosmid- and BAC-end sequences produced the best continuity (~3.7 Mb in
      N50 scaffold size) among the sequenced insect genomes and provided a high degree
      of nucleotide coverage (88%) of all 28 chromosomes. In addition, a physical map
      of BAC contigs constructed by fingerprinting BAC clones and a SNP linkage map
      constructed using BAC-end sequences were available. In parallel, proteomic data
      from two-dimensional polyacrylamide gel electrophoresis in various tissues and
      developmental stages were compiled into a silkworm proteome database. Finally, a
      Bombyx trap database was constructed for documenting insertion positions and
      expression data of transposon insertion lines. CONCLUSION: For efficient usage of
      genome information for functional studies, genomic sequences, physical and
      genetic map information and EST data were compiled into KAIKObase, an integrated
      silkworm genome database which consists of 4 map viewers, a gene viewer, and
      sequence, keyword and position search systems to display results and data at the
      level of nucleotide sequence, gene, scaffold and chromosome. Integration of the
      silkworm proteome database and the Bombyx trap database with KAIKObase led to a
      high-grade, user-friendly, and comprehensive silkworm genome database which is
      now available from URL: http://sgp.dna.affrc.go.jp/KAIKObase/.

PMID- 19843345
TI  - A randomized single blind crossover trial comparing leather and commercial wrist
      splints for treating chronic wrist pain in adults.
AB  - BACKGROUND: To compare the effectiveness of a custom-made leather wrist splint
      (LS) with a commercially available fabric splint (FS) in adults with chronic
      wrist pain. METHODS: Participants (N = 25, mean age = 54) were randomly assigned
      to treatment order in a 2-phase crossover trial. Splints were worn for 2 weeks,
      separated by a one-week washout period. Outcomes were assessed at baseline and
      after each splint phase using the Australian/Canadian Osteoarthritis Hand Index
      (AUSCAN), the Canadian Occupational Performance Measure (COPM) and Jamar
      dynamometer by an observer blinded to treatment allocation. RESULTS: Both styles
      of wrist splint significantly reduced pain (effect size LS 0.79, FS 0.43),
      improved hand function and increased grip strength compared to baseline (all p <
      0.05) with no increase in wrist stiffness. There was a consistent trend for the
      LS to be superior to the FS but this was statistically significant only for
      patient perceived occupational performance (p = 0.008) and satisfaction (p =
      0.015). Lastly, 72% of patients preferred the custom-made leather splint compared
      to the commercially available splint. CONCLUSION: Leather wrist splints were
      superior to a commercially available fabric splint for the short-term relief of
      pain and dysfunction.

PMID- 19843346
TI  - Chronic disease prevalence and care among the elderly in urban and rural Beijing,
      China - a 10/66 Dementia Research Group cross-sectional survey.
AB  - BACKGROUND: Demographic ageing is occurring at an unprecedented rate in China.
      Chronic diseases and their disabling consequences will become much more common.
      Public policy has a strong urban bias, and older people living in rural areas may
      be especially vulnerable due to limited access to good quality healthcare, and
      low pension coverage. We aim to compare the sociodemographic and health
      characteristics, health service utilization, needs for care and informal care
      arrangements of representative samples of older people in two Beijing
      communities, urban Xicheng and rural Daxing. METHODS: A one-phase cross-sectional
      survey of all those aged 65 years and over was conducted in urban and rural
      catchment areas in Beijing, China. Assessments included questionnaires, a
      clinical interview, physical examination, and an informant interview. Prevalence
      of chronic diseases, self-reported impairments and risk behaviours was calculated
      adjusting for household clustering. Poisson working models were used to estimate
      the independent effect of rural versus urban residence, and to explore the
      predictors of health services utilization. RESULTS: We interviewed 1002
      participants in rural Daxing, and 1160 in urban Xicheng. Those in Daxing were
      more likely to be younger, widowed, less educated, not receiving a pension, and
      reliant on family transfers. Chronic diseases were more common in Xicheng, when
      based on self-report rather than clinical assessment. Risk exposures were more
      common in Daxing. Rural older people were much less likely to access health
      services, controlling for age and health. Community health services were
      ineffective, particularly in Daxing, where fewer than 3% of those with
      hypertension were adequately controlled. In Daxing, care was provided by family,
      who had often given up work to do so. In Xicheng, 45% of those needing care were
      supported by paid caregivers. Caregiver strain was higher in Xicheng. Dementia
      was strongly associated with care needs and caregiver strain, but not with
      medical helpseeking. CONCLUSION: Apparent better health in Daxing might be
      explained by under-diagnosis, under-reporting or selective mortality. Far
      reaching structural reforms may be needed to improve access and strengthen rural
      healthcare. The impact of social and economic change is already apparent in
      Xicheng, with important implications for future long-term care.

PMID- 19843347
TI  - Microsatellite markers of water buffalo, Bubalus bubalis--development,
      characterisation and linkage disequilibrium studies.
AB  - BACKGROUND: Microsatellite markers are highly polymorphic and widely used in
      genome mapping and population genetic studies in livestock species. River
      buffalo, Bubalus bubalis is an economically important livestock species, though
      only a limited number of microsatellite markers have been reported thus far in
      this species. RESULTS: In the present study, using two different approaches 571
      microsatellite markers have been characterized for water buffalo. Of the 571
      microsatellite markers, 498 were polymorphic with average heterozygosity of 0.51
      on a panel of 24 unrelated buffalo. Fisher exact test was used to detect LD
      between the marker pairs. Among the 137550 pairs of marker combination, 14.58%
      pairs showed significant LD (P < 0.05). Further to check the suitability of these
      microsatellite markers to map these on a radiation hybrid map of buffalo genome,
      the markers were tested on Chinese hamster genomic DNA for amplification. Only
      seven of these markers showed amplification in Chinese hamster, and thus 564, of
      these can be added to the radiation hybrid map of this species. CONCLUSION: The
      high conservation of cattle microsatellite loci in water buffalo promises the
      usefulness of the cattle microsatellites markers on buffalo. The polymorphic
      markers characterised in this study will contribute to genetic linkage and
      radiation hybrid mapping of water buffalo and population genetic studies.

PMID- 19843348
TI  - Human APOBEC1 cytidine deaminase edits HBV DNA.
AB  - Retroviruses, hepadnaviruses, and some other retroelements are vulnerable to
      editing by single stranded DNA cytidine deaminases. Of the eleven human genes
      encoding such enzymes, eight have demonstrable enzymatic activity. Six of seven
      human APOBEC3 are able to hyperedit HBV DNA, frequently on both strands. Although
      human APOBEC1 (hA1) is not generally expressed in normal liver, hA1 can edit
      single stranded DNA in a variety of experimental assays. The possibility of
      ectopic expression of hA1 in vivo cannot be ruled out and interestingly,
      transgenic mice with A1 expressed under a liver specific promoter develop
      hepatocellular carcinoma. The impact of hA1 on HBV in tissue culture is varied
      with reports noting either reduced DNA synthesis or not, with cytidine
      deamination taking a low profile. We sought to examine the hA1 editing activity
      on replicating HBV. Using highly sensitive 3DPCR it was possible to show that hA1
      edits the HBV minus DNA strand as efficiently as hA3G, considered the reference
      deaminase for HIV and HBV. The dinucleotide specificity of editing was unique
      among human cytidine deaminases providing a hallmark of use in a posteriori
      analyses of in vivo edited genomes. Analysis of sequences derived from the serum
      of two chronic carriers, indicated that hA1 explained only a small fraction of
      edited HBV genomes. By contrast, several human APOBEC3 deaminases were active
      including hA3G.

PMID- 19843349
TI  - Runaway repeats force expansion of the Phytophthora infestans genome.
AB  - Sequencing of the genome of the potato late blight pathogen Phytophthora
      infestans provides insight into genome structure and evolution within this genus
      of plant pathogenic oomycetes.

PMID- 19843351
TI  - The positive feedback bias as a response to self-image threat.
AB  - This research examined whether Whites favourably bias their feedback to
      minorities in order to see themselves as egalitarian. White teacher trainees
      first had their egalitarian self-images affirmed, left unchanged, or threatened.
      They then provided feedback on a poorly written essay supposedly authored by
      either a Black or a White student. As predicted, trainees in the Black
      writer/self-image threat condition selectively rated essay content more
      favourably, recommended less time for skill development, provided more favourable
      copy-editing comments, and generated more equivocating 'buffers'. In contrast,
      trainees in the Black writer/self-image boost condition supplied feedback
      indistinguishable from feedback provided by trainees in the White writer
      conditions, which was unaffected by the self-image conditions. The implications
      for minority education and intergroup communication are discussed.

PMID- 19843350
TI  - FMRFamide-like peptides in root knot nematodes and their potential role in
      nematode physiology.
AB  - FMRFamide-like peptides (FLPs) are a diverse group of neuropeptides that are
      expressed abundantly in nematodes. They exert potent physiological effects on
      locomotory, feeding and reproductive musculature and also act as neuromodulators.
      However, little is known about the specific expression patterns and functions of
      individual peptides. The current study employed rapid amplification of cDNA ends
      polymerase chain reaction (RACE-PCR) to characterize flp genes from infective
      juveniles of the root knot nematodes, Meloidogyne incognita and Meloidogyne
      minor. The peptides identified from these transcripts are sequelogs of FLPs from
      the free-living nematode, Caenorhabditis elegans; the genes have therefore been
      designated as Mi-flp-1, Mi-flp-7, Mi-flp-12, Mm-flp-12 and Mi-flp-14. Mi-flp-1
      encodes five FLPs with the common C-terminal moiety, NFLRFamide. Mi-flp-7 encodes
      two copies of APLDRSALVRFamide and APLDRAAMVRFamide and one copy of
      APFDRSSMVRFamide. Mi-flp-12 and Mm-flp-12 encode the novel peptide
      KNNKFEFIRFamide (a longer version of RNKFEFIRFamide found in C. elegans). Mi-flp
      14 encodes a single copy of KHEYLRFamide (commonly known as AF2 and regarded as
      the most abundant nematode FLP), and a single copy of the novel peptide
      KHEFVRFamide. These FLPs share a high degree of conservation between Meloidogyne
      species and nematodes from other clades, including those of humans and animals,
      perhaps suggesting a common neurophysiological role which may be exploited by
      novel drugs. FLP immunoreactivity was observed for the first time in Meloidogyne,
      in the circumpharyngeal nerve ring, pharyngeal nerves and ventral nerve cord.
      Additionally, in situ hybridization revealed Mi-flp-12 expression in an RIR-like
      neuron and Mi-flp-14 expression in SMB-like neurons, respectively. These
      localizations imply physiological roles for FLP-12 and FLP-14 peptides, including
      locomotion and sensory perception.

PMID- 19843352
TI  - Measurement of ability emotional intelligence: results for two new tests.
AB  - Emotional intelligence (EI) has attracted considerable interest amongst both
      individual differences researchers and those in other areas of psychology who are
      interested in how EI relates to criteria such as well-being and career success.
      Both trait (self-report) and ability EI measures have been developed; the focus
      of this paper is on ability EI. The associations of two new ability EI tests with
      psychometric intelligence, emotion perception, and the Mayer-Salovey-Caruso EI
      test (MSCEIT) were examined. The new EI tests were the Situational Test of
      Emotion Management (STEM) and the Situational Test of Emotional Understanding
      (STEU). Only the STEU and the MSCEIT Understanding Emotions branch were
      significantly correlated with psychometric intelligence, suggesting that only
      understanding emotions can be regarded as a candidate new intelligence component.
      These understanding emotions tests were also positively correlated with emotion
      perception tests, and STEM and STEU scores were positively correlated with MSCEIT
      total score and most branch scores. Neither the STEM nor the STEU were
      significantly correlated with trait EI tests, confirming the distinctness of
      trait and ability EI. Taking the present results as a starting-point, approaches
      to the development of new ability EI tests and models of EI are suggested.

PMID- 19843353
TI  - A qualitative analysis of mindfulness-based cognitive therapy (MBCT) in
      Parkinson's disease.
AB  - OBJECTIVES: To analyse the experiences of participants with Parkinson's disease
      (PD), who participated in an 8-week mindfulness-based cognitive therapy (MBCT)
      course. DESIGN AND METHOD: Interpretative phenomenological analysis guided the
      design and method used in this study. A total of twelve participants (seven men
      and five women) with PD were recruited prior to and following participation in an
      MBCT course and interviewed with a semi-structured interview schedule. One
      participant who opted out of the course was also interviewed. The researcher also
      participated in another MBCT course to enhance their understanding of the
      participants' experience, keeping a detailed diary as a means of acknowledging
      bias in the analysis process. Themes were summarized from transcripts and later
      classified into superordinate themes, which were compared across all cases.
      Transcripts were also read and analysed by a second author and participants were
      given the opportunity to comment upon emerging themes. RESULTS: Major themes
      included (1) changing patterns of coping; (2) the role of mindfulness in
      consolidating existing coping skills in the context of loss; (3) group support in
      the context of loss and society that stigmatizes difference; and (4) the dualism
      of experience between Parkinson's and mindful meditation. CONCLUSIONS: This study
      has indicated that MBCT could benefit people with PD and was an acceptable form
      of group intervention.

PMID- 19843354
TI  - A randomized trial of face-to-face counselling versus telephone counselling
      versus bibliotherapy for occupational stress.
AB  - OBJECTIVE: The aim of the present study was to compare the effectiveness and
      acceptability of three interventions for occupational stress. METHODS/DESIGN: A
      total of 90 National Health Service employees were randomized to face-to-face
      counselling or telephone counselling or bibliotherapy. Outcomes were assessed at
      post-intervention and 4-month follow-up. Clinical Outcomes in Routine Evaluation
      (CORE), General Health Questionnaire (GHQ-12), and Perceived Stress Scale (PSS
      10) were used to evaluate intervention outcomes. An intention-to-treat analyses
      was performed. RESULTS: Repeated measures analysis revealed significant time
      effects on all measures with the exception of CORE Risk. No significant group
      effects were detected on all outcome measures. No time by group significant
      interaction effects were detected on any of the outcome measures with the
      exception of CORE Functioning and GHQ total. With regard to acceptability of
      interventions, participants expressed a preference for face-to-face counselling
      over the other two modalities. CONCLUSIONS: Overall, it was concluded that the
      three intervention groups are equally effective. Given that bibliotherapy is the
      least costly of the three, results from the present study might be considered in
      relation to a stepped care approach to occupational stress management with
      bibliotherapy as the first line of intervention, followed by telephone and face
      to-face counselling as required.

PMID- 19843357
TI  - Gold nanoparticle based surface-enhanced Raman scattering spectroscopy of
      cancerous and normal nasopharyngeal tissues under near-infrared laser excitation.
AB  - The capabilities of using gold nanoparticle based near-infrared surface-enhanced
      Raman scattering (SERS) to obtain biochemical information with high spatial
      resolution from human nasopharyngeal tissue were presented in this paper. The
      gold nanoparticles used have a mean diameter of 43 nm with a standard deviation
      of 6 nm. The SERS bands of nasopharyngeal tissue were assigned to known molecular
      vibrations of nucleic acids, amino acids, proteins, and metabolites. We also
      observed the blinking phenomenon at the tissue level when measuring the
      nasopharyngeal tissue SERS spectra, most frequently in signal intensity but also
      occasionally in peak positions. This phenomenon is excitation light intensity
      dependent. This work demonstrated great potential for using SERS imaging for
      distinguishing cancerous and normal nasopharyngeal tissues on frozen sections
      without using any dye labeling or other chemical species as functionalized
      binding sites.

PMID- 19843358
TI  - Differentiation of healthy brain tissue and tumors using surface-enhanced Raman
      scattering.
AB  - Surface-enhanced Raman scattering (SERS) is a powerful technique for
      characterization of biological samples. SERS spectra from healthy brain tissue
      and tumors are obtained by sudden freezing of tissue in liquid nitrogen and
      crashing and mixing it with a concentrated silver colloidal suspension. The
      acquired spectra from tissues show significant spectral differences that can be
      used to identify whether it is from a healthy region or tumor. The most
      significant change on SERS spectra from the healthy/peripheral brain tissue to
      tumor is the increase of the ratio of the peaks at around 723 to 655 cm(-1). In
      addition, the spectral changes indicate that the protein content in tumors
      increases compared to the peripheral/healthy tissue as observed with tumor
      invasion. The preliminary results show that SERS spectra can be used for a quick
      diagnosis due to the simplicity of the sample preparation and the speed of the
      spectral acquisition.

PMID- 19843359
TI  - Patterned silver nanorod array substrates for surface-enhanced Raman scattering.
AB  - A novel method for batch fabrication of substrates for surface-enhanced Raman
      scattering (SERS) has been developed. A modified platen that fits in a commercial
      electron beam evaporator enables the simultaneous deposition of Ag nanorod arrays
      onto six microscope slides by glancing angle deposition. Following removal of
      substrates from the evaporator, patterned wells are formed by contact printing of
      a polymer onto the surface. Well dimensions are defined by penetration of the
      polymer into the nanorod array and subsequent photochemical curing. Inherent
      advantages of this method include: (1) simultaneous production of several nanorod
      array substrates with high structural uniformity, (2) physical isolation of
      nanorod arrays from one another to minimize cross contamination during sample
      loading, (3) dimensional compatibility of the patterned array with existing SERS
      microscope, (4) large SERS enhancement afforded by the nanorod array format, (5)
      small fluid volumes, and (6) ease of use for manual delivery of fluids to each
      element in the patterned array. In this article, the well-to-well, slide-to
      slide, and batch-to-batch variability in physical characteristics and SERS
      response of substrates prepared via this method is critically examined.

PMID- 19843361
TI  - Light sheet direct Raman imaging technique for observation of mixing of solvents.
AB  - The light sheet direct Raman (LSDR) imaging technique is used to obtain wide
      scope, simultaneous images of samples emitting Raman scattered light, without
      mapping their point-to-point Raman scattering intensities. A prototype system
      consisting of a background-free electronically tuned Ti:sapphire laser (BF-ETL),
      band-pass (BP) filters, and a charge-coupled device (CCD) detector is developed
      in the present study. The LS excitation method enables us to obtain a wide field
      of Raman view. The BF-ETL allows us to obtain direct Raman images with multiple
      Raman bands without the need for rearranging the optical settings. The system is
      used to observe the mixing of pure solvents: carbon tetrachloride (CCl(4)) and
      chloroform (CHCl(3)), and ethylene glycol (EG) and polyethylene glycol (PEG).
      LSDR images are successfully obtained within an exposure time of 0.5 s. EG and
      PEG, whose Raman spectra appear similar, can be distinguished clearly in the
      images, suggesting that the system has high spectral resolution.

PMID- 19843360
TI  - Quantitative surface-enhanced Raman spectroscopy based analysis of microRNA
      mixtures.
AB  - We have developed a rapid, sensitive, and quantitative method for identification
      of microRNA (miRNA) sequences in multicomponent mixtures using surface-enhanced
      Raman spectroscopy (SERS). The method uses Ag nanorod array substrates prepared
      by oblique angle vapor deposition as the SERS platform. We show that Ag nanorod
      based SERS spectra are uniquely characteristic for each miRNA sequence studied,
      and that the spectral reproducibility is sufficient for quantitative analysis of
      miRNA profiles in multicomponent mixtures using partial least squares (PLS)
      regression analysis. This method was applied to individual sample mixtures
      consisting of two, three, and five miRNAs. Separate PLS models were generated for
      the two-, three-, and five-component mixtures from >150 calibration spectra
      covering a concentration range of 6 to 150 microM for each miRNA. The PLS models
      were externally validated with independent test samples resulting in root mean
      square errors of prediction (RMSEP) of 7.4, <7.4, and <10 microM for the two-,
      three-, and five-component models, respectively. These results demonstrate the
      applicability of SERS for quantitative detection and profiling of miRNAs and
      suggest that SERS may prove to be a novel, label-free method for identification
      of disease biomarkers.

PMID- 19843362
TI  - Investigation of hydrogenation of toluene to methylcyclohexane in a trickle bed
      reactor by low-field nuclear magnetic resonance spectroscopy.
AB  - Low-field nuclear magnetic resonance (NMR) spectroscopy is applied to study the
      hydrogenation of toluene in a lab-scale reactor. A conventional benchtop NMR
      system was modified to achieve chemical shift resolution. After an off-line
      validity check of the approach, the reaction product is analyzed on-line during
      the process, applying chemometric data processing. The conversion of toluene to
      methylcyclohexane is compared with off-line gas chromatographic analysis. Both
      classic analytical and chemometric data processing was applied. As the results,
      which are obtained within a few tens of seconds, are equivalent within the
      experimental accuracy of both methods, low-field NMR spectroscopy was shown to
      provide an analytical tool for reaction characterization and immediate feedback.

PMID- 19843363
TI  - Complete theoretical treatment of the transmittance ratio ultraviolet/visible
      spectrophotometric stray radiant energy test method.
AB  - This paper develops the theoretical basis behind the transmittance ratio test
      method for determining the relative stray radiant energy level in a double-beam
      dispersive spectrophotometer so as to allow for the non-transparency of a test
      solution towards the stray radiant energy for all sample beam-to-reference beam
      cuvette path length ratios. Non-transparency is defined as the transmittance of
      the reference beam solution, whose monochromatic absorbance is unity, towards
      stray radiant energy. The proposed method has the same concentration absorbing
      sample placed in the beams of the scanning spectrophotometer, the sample-beam
      cuvette being a known factor longer than the reference-beam cuvette. While
      scanning towards shorter wavelengths, an apparent differential absorbance Mielenz
      peak is recorded. An exact formula is derived in this paper relating the relative
      stray radiant energy level to the Mielenz peak absorbance, to the known cuvette
      path length ratio, to the observed monochromatic absorbance of the test sample at
      the Mielenz peak wavelength, and to the sample transmittance towards the stray
      radiant energy. Sample transmittance towards stray radiant energy cannot be
      determined experimentally. However, the derived formula only allows the other
      experimental quantities to tie in together for a single numerically calculated
      value for the sample-transmittance towards stray radiant energy. The formulae are
      tedious to derive and cumbersome to handle, but their application is facilitated
      greatly by a Microsoft Office Excel 2007 spreadsheet. The test method was applied
      to an ultraviolet-visible (UV/VIS) scanning spectrophotometer at nine wavelengths
      in the range 713 > lambda (nm) >; 649 for a sample beam-to-reference beam cuvette
      path length ratio of 10 mm/5 mm and using blue food dye (E123) as the test
      material. Sample transparency to stray radiant energy fluctuated in wavelength
      between 0.819 and 0.948, while the relative stray radiant energy level fluctuated
      between 1.283 x 10(-3) and 2.516 x 10(-3). The investigation was repeated at
      665.6 nm for all fifteen sample beam-to-reference beam cuvette path length
      ratios, which it was possible to establish using combinations of quartz-glass
      cuvettes with path lengths of 100, 50, 20, 10, 5, 2, and 1 mm. The sample
      transparency to stray radiant energy at 665.6 nm was 0.95 +/- 0.5, while the
      relative stray radiant energy was (1.5 +/- 0.33) x 10(-3).

PMID- 19843364
TI  - Effects of added minerals (calcium, phosphate, and citrate) on the molecular
      structure of skim milk as investigated by mid-infrared and synchronous
      fluorescence spectroscopies coupled with chemometrics.
AB  - Minerals play an important role in the structure and stability of casein
      micelles: minerals and caseins in milk are in dynamic equilibrium. Front-face
      synchronous fluorescence and mid-infrared spectra in combination with
      multivariate statistical analysis have been used to investigate, at a molecular
      level, the effects of added minerals (calcium, phosphate, or citrate) on mineral
      equilibria and casein micelle structure. Synchronous fluorescence spectra were
      recorded in the 250-500 nm excitation wavelength range using an offset of 80 nm
      between the excitation and emission monochromators for skim-milk samples
      fortified with 0, 3, 6, and 9 mM of calcium, phosphate, or citrate at 30 degrees
      C and 4 degrees C. Regarding midinfrared spectroscopy, the region located between
      1700-1500 cm(-1), corresponding to the amide I and II bands, and the 1500-900 cm(
      1) region, called the fingerprint region, were considered for the
      characterization of the fortified skim-milk samples at the two considered
      temperatures. Principal component analysis (PCA) was applied to the collections
      of fluorescence and infrared spectral data of the two systems to optimize their
      description. The results show that the phenomena induced by the addition of
      phosphate were different from the ones observed following the addition of calcium
      or citrate, a calcium-chelating agent. Finally, common components and specific
      weights analysis was applied to infrared spectra and fluorescence data collected
      on fortified skim-milk samples. This analysis enabled the relationship between
      the different data tables to be established.

PMID- 19843365
TI  - Recovering independent components from shifted data using fast independent
      component analysis and swarm intelligence.
AB  - Frequency displacement, or spectral shift, is commonly observed in industrial
      spectral measurements. It can be caused by many factors such as sensor de
      calibration or by external influences, which include changes in temperature. The
      presence of frequency displacement in spectral measurements can cause
      difficulties when statistical techniques, such as independent component analysis
      (ICA), are used to analyze it. Using simulated spectral measurements, this paper
      initially highlights the effect that frequency displacement has on ICA. A post
      processing technique, employing particle swarm optimization (PSO), is then
      proposed that enables ICA to become robust to frequency displacement in spectral
      measurements. The capabilities of the proposed approach are illustrated using
      several simulated examples and using tablet data from a pharmaceutical
      application.

PMID- 19843366
TI  - Determination of phase transition temperatures by the analysis of baseline
      variations in transmittance infrared spectroscopy.
AB  - A simple method for obtaining phase transition temperatures is proposed. It is
      based on absolute variations of a baseline in a temperature-dependent mid
      infrared transmittance spectral data set recorded for a sample KBr pellet. The
      method is rapid, inexpensive, and completely free of any personal bias. The
      method efficiency was corroborated by measuring the phase transitions of
      mesomorphic (trans-4-heptyl cyclohexanecarboxylic acid) and polymorphic compounds
      (polycyclic aromatic hydrocarbons and phenylacetylenes). In addition, the
      exothermic decomposition of phenylacetylenes was also monitored, thereby opening
      the possibility for simple and rapid monitoring of chemical reactions in solid
      and liquid phase. A great prospect of the method as an economical way of
      establishing critical temperature regions for analytical and quality control
      purposes is foreseen.

PMID- 19843367
TI  - Attenuated total reflection surface-enhanced infrared absorption spectroscopy at
      a cobalt electrode.
AB  - In situ surface-enhanced infrared absorption spectroscopy (SEIRAS) in attenuated
      total reflection (ATR) configuration has been extended to a Co electrode
      fabricated by potentiostatic deposition of a 50-nm-thick Co overlayer onto a Au
      underlayer chemically preformed on the reflecting plane of an ATR Si hemi
      cylindrical prism. The as-prepared Co-on-Au film was characterized with atomic
      force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The AFM images
      of the films before and after Co coating revealed island structures facilitating
      the SEIRA effect with Co nanoparticles much smaller than the underlying Au ones.
      The XPS spectrum did not contain any characteristic peaks related to Au,
      suggestive of a virtually pinhole-free nature of the Co overlayer. The
      voltammetric response of the as-prepared films in phosphate buffer solution (PBS,
      pH 6.9) was characteristic of a polycrystalline bulk Co electrode. Normally
      directed unipolar bands were found for surface probe CO molecules on Co surfaces
      in the PBS with their major band (CO(L)) intensity being one order of magnitude
      higher than that obtained with conventional IR reflection-absorption spectroscopy
      (IRRAS). By taking advantage of the higher detection sensitivity, the bands for
      linearly bonded CO (CO(L)) at 1965-2005 cm(-1) and the multi-bonded (CO(M)) band
      at 1845-1875 cm(-1) were clearly detected with their Stark tuning rates being 59
      and 63 cm(-1) x V(-1), respectively, which would be otherwise unobtainable with
      the conventional IRRAS in the neutral solution.

PMID- 19843368
TI  - In situ evaluation of net nitrification rate in Terra rossa soil using a Fourier
      transform infrared attenuated total reflection 15N tracing technique.
AB  - Nitrification and mineralization of organic nitrogen (N) are important N
      transformation processes in soil, and mass spectrometry is a suitable technique
      for tracing changes of (15)N isotopic species of mineral N and estimating the
      rates of these processes. However, mass spectrometric methods for tracing N
      dynamics are costly, time consuming, and require long and laborious preparation
      procedures. This study investigates mid-infrared attenuated total reflection
      (ATR) spectroscopy as an alternative method for detecting changes in (14)NO(3)-N
      and (15)NO(3)-N concentrations. There is a significant shift of the nu(3)
      absorption band of nitrate according to N species, namely from the 1275 to 1460
      cm(-1) region for (14)NO(3)(-) to the 1240-1425 cm(-1) region for (15)NO(3). This
      shift makes it possible to quantify the N isotopes using multivariate calibration
      methods. Partial least squares regression (PLSR) models with five factors yielded
      a determination error of 6.7-9.2 mg N L(-1) for aqueous solutions and 5.9-7.8 mg
      N kg(-1) (dry soil) for pastes of a Terra rossa soil. These PLSR models were used
      to monitor the changes of (15)NO(3)-N and (14)NO(3)-N content in the same Terra
      rossa soil during an incubation experiment in which [(15)NH(4)](2)SO(4) was
      applied to the soil, allowing the estimation of the contributions of applied N
      and mineralized N to the net nitrification rate, the potential losses of the
      applied (15)NH(4)-N, and the net mineralization of soil organic N.

PMID- 19843369
TI  - Thermally induced dissociation nature of pure 2-pyrrolidinone via near-infrared
      correlation spectroscopy analysis.
AB  - The temperature-dependent dissociation behavior of 2-pyrrolidinone in the pure
      liquid state was investigated via perturbation-correlation moving-window two
      dimensional (PCMW2D) correlation spectroscopy and two-dimensional near-infrared
      (2D-NIR) correlation spectroscopy. Absorption bands in the region of 6900-6000
      cm(-1) assigned to the first overtones of stretching modes of NH groups provided
      detailed information about the dissociation process from 25 degrees C to 95
      degrees C. On the basis of PCMW2D analysis, the sequence of dissociation events
      occurring during the temperature variation were elucidated in two temperature
      ranges (25-60 degrees C and 65-95 degrees C). Specific dissociation order of the
      hydrogen bond under temperature perturbation was disclosed by 2D-NIR correlation
      spectroscopy. As temperature increased, the dissociation of larger oligomers
      occurred firstly with the generation of smaller oligomers, which were then
      consumed later by the decomposition of hydrogen bonds. The dissociation of stable
      cyclic dimers occurred mainly at higher temperature through gradually weakened
      hydrogen-bonding of NH groups.

PMID- 19843370
TI  - Demountable liquid/flow cell for in vivo infrared microspectroscopy of biological
      specimens.
AB  - We have developed a liquid/flow cell/chamber allowing infrared measurements of
      living biological specimens with high spatial resolution under a controlled
      aqueous environment. This flow chamber features sub-micrometer thick diamond
      windows exhibiting low spherical and chromatic aberrations. Diamond has excellent
      transmission properties and minimal dispersion over the entire mid-infrared and
      visible spectral ranges. In contrast to current commercially available infrared
      liquid chambers, the flow chamber has a slim profile, which accommodates high
      resolution/magnification microscope objectives with small working distances, down
      to 0.6 mm above the chamber and 6 mm below the flow chamber. We have coupled a
      pump to the flow chamber to provide medium exchange. As an example, we present
      microspectroscopic infrared maps and spectra of the freshwater green alga
      Micrasterias sp. in the new flow chamber and compare them to maps obtained with a
      conventional liquid chamber. Pulse-amplitude-modulated fluorescence measurements
      on Micrasterias sp. cells inside the new flow chamber have been evaluated to
      demonstrate the viability of the algal cells.

PMID- 19843371
TI  - Assessment of the titanium dioxide absorption coefficient by grazing-angle
      Fourier transform infrared and ellipsometric measurements.

PMID- 19843372
TI  - Transfer of calibrations for barley quality from dispersive instrument to Fourier
      transform near-infrared instrument.

PMID- 19843373
TI  - A role for acute-phase serum amyloid A and high-density lipoprotein in oxidative
      stress, endothelial dysfunction and atherosclerosis.
AB  - The acute-phase protein serum amyloid A (SAA) is a clinically useful marker of
      inflammation and associates strongly with increased risk of cardiovascular
      events. Chronically elevated SAA concentrations may contribute to physiological
      processes that lead to atherosclerosis, including endothelial dysfunction, an
      early and predictive event in the development of cardiovascular disease.
      Accumulating data suggest that SAA can be a direct mediator in the development
      and progression of atherogenesis and atherothrombosis. SAA may affect key events
      underlying acute coronary syndromes, including cholesterol transport, contribute
      to endothelial dysfunction, promote thrombosis, and enhance leukocyte trafficking
      and activation. This review summarizes the evidence supporting a role for SAA as
      a potential regulator of inflammation and endothelial dysfunction, which underlie
      the adverse outcomes that complicate coronary artery disease. The findings
      suggest that novel therapeutic strategies to reduce SAA levels and/or oppose the
      actions of SAA may have beneficial effects in patients with coronary artery
      disease.

PMID- 19843374
TI  - Improved peroxyl radical scavenging TOSC assay to quantify antioxidant capacity
      using SIFT-MS.
AB  - We report a new, fast, sensitive variation of the total oxyradical scavenging
      capacity (TOSC) assay for measuring the antioxidant capacity of pure compounds,
      plant extracts and biological fluids using selected ion flow tube mass
      spectrometry (SIFT-MS). The TOSC assay examines the partial inhibition of ethene
      formation in the presence of antioxidants that compete with alpha-keto-gamma
      methiolbutyric acid (KMBA) for reactive oxygen species. The SIFT-MS-TOSC assay
      takes 15 s for each ethene analysis and the time interval between consecutive
      analyses is 20 s. We demonstrate the method by monitoring the antioxidant
      capacity of several standard radical scavengers of peroxyl radicals. For peroxyl
      radicals the measured SIFT-MS-TOSC concentrations necessary to produce 50%
      inhibition of radical reaction with KMBA are 6.1 +/- 0.3 microM for Trolox, 5.7
      +/- 0.3 microM for ascorbic acid, 8.4 +/- 0.4 microM for uric acid and 38 +/- 2
      microM for reduced glutathione.

PMID- 19843375
TI  - The interaction between follicular fluid total antioxidant capacity, infertility
      and early reproductive outcomes during in vitro fertilization.
AB  - INTRODUCTION: The objective of this study was to determine whether the
      relationship between antioxidant capacity of follicular fluid and early
      reproductive outcomes is influenced by the cause of infertility, polycystic
      ovarian morphology, age and smoking. PATIENTS AND METHODS: This was a
      prospective, cross-sectional study performed in an assisted conception unit and a
      teaching hospital. The study cohort was 34 women undergoing IVF treatment.
      Interventions included total antioxidant capacity (TAC) measured using ferric
      reducing/antioxidant power assay in 303 follicular fluid samples. The main
      outcome measures were follicular fluid TAC, percentage TAC loss after 72 h and
      early reproductive outcomes. RESULTS: Follicular TAC was elevated in women with
      infertility of 'unexplained' (UE) or tubal factor (TF) aetiology, relative to
      those with male factor (MF) infertility, when reproductive outcomes were positive
      but not when they were negative. In the TF and UE groups, low TAC was associated
      with ovum fertilization incompetence, whereas TAC was comparable irrespective of
      embryo viability. Unexplained infertility was associated with significantly
      elevated follicular TAC. Among women with polycystic ovaries, fertilization
      incompetence was associated with elevated TAC; the opposite was true in women
      with normal ovaries. Follicular fluid 72-h TAC consumption > 20% was associated
      with poorer reproductive performance. CONCLUSIONS: The follicular fluid pro
      oxidant-antioxidant balance required for conception in women undergoing IVF is
      related to the aetiology of infertility, age, the presence of polycystic ovary
      morphology and smoking.

PMID- 19843376
TI  - Buffer modulation of menadione-induced oxidative stress in Saccharomyces
      cerevisiae.
AB  - The objective of this study was to compare, in vivo, the effects of bicarbonate
      and phosphate buffers on survival and menadione-induced oxidative stress in yeast
      cells. The latter were treated with different concentrations of menadione in the
      presence of these two buffers. At 25 mM concentration of buffers, menadione only
      slightly reduced yeast surviving; at 50 mM concentration, cell killing by
      menadione was much more pronounced in bicarbonate than in phosphate buffer.
      Although the content of protein carbonyl groups did not show development of
      oxidative stress under menadione-induced stress, inactivation of aconitase and
      decrease in glutathione level mirrored its induction. However, cellular
      glutathione and aconitase activity decrease did not correlate with yeast
      survival. In vitro, aconitase was more quickly inactivated in 50 mM carbonate,
      than in 50 mM phosphate buffer. The possible involvement of the carbonate radical
      in these processes is discussed.

PMID- 19843377
TI  - Antioxidant supplementation lowers circulating IGF-1 but not F(2)-isoprostanes
      immediately following anterior cruciate ligament surgery.
AB  - Interleukin (IL)-10 is an anti-inflammatory cytokine that suppresses pro
      inflammatory cytokines. We previously demonstrated that supplementation with
      vitamins E and C ameliorated the increase in IL-10 immediately following anterior
      cruciate ligament (ACL) surgery in the absence of other cytokine perturbations.
      Since both oxidative stress and insulin-like growth factor-1 (IGF-1) can modulate
      IL-10 concentrations, the mechanisms for these changes warranted further
      investigation. Our objective was to evaluate the mechanism for the IL-10 decrease
      following ACL surgery. This study consisted of randomized, double-blind, placebo
      controlled experimental design. Subjects were randomly assigned to daily
      supplementation with either: (i) antioxidants (AO; vitamins E [alpha-tocopherol]
      and C [ascorbic acid]; n = 10); or (ii) matching placebos (PL; n = 10).
      Supplementation started approximately 2 weeks prior to surgery (baseline) and
      concluded 3 months after surgery. Subjects provided six fasting blood samples at:
      (i) baseline; (ii) immediately pre-surgery (Pre); (iii) 90 min; (iv) 72 h; (v) 7
      days; and (vi) 3 months post-surgery. alpha-Tocopherol, ascorbic acid, F(2)
      isoprostane and IGF-1 concentrations were measured in each blood sample. At 90
      min relative to other times, plasma F(2)-isoprostane concentrations were
      significantly (P < 0.05) elevated in both groups, while at 90 min IGF-1 was
      significantly (P < 0.05) lower in the AO compared to the PL group. The changes in
      IGF-1 at 90 min relative to baseline were correlated (P < 0.0001) with the
      changes in IL-10. The decrease in IL-10 observed in the AO group is likely
      dependent on the decrease IGF-1 since lipid peroxidation was unchanged between
      the two groups.

PMID- 19843378
TI  - Modern concepts in the treatment of chronic lymphocytic leukemia.
AB  - There has been considerable progress in the treatment of chronic lymphocytic
      leukemia (CLL) during last 10 years. Purine analogs and monoclonal antibodies
      have enabled the shift from purely palliative treatment to intensive regimens
      aiming at complete remissions and possible prolongation of survival. Many
      patients have now been shown to achieve molecular responses in addition to their
      hematological remission. Despite this success, virtually all patients with CLL
      will eventually relapse and will become refractory to treatment. Allogeneic stem
      cell transplantation offers a chance of definite cure but is feasible in a
      minority of patients only. Therefore, considerable effort has been devoted to the
      further development of more conventional CLL management that is applicable to
      patient population generally affected by the disease. Emerging treatment concepts
      include novel combination of well-know agents such as rituximab and chlorambucil,
      fludarabine, cyclophosphamide and alemtuzumab, FCR with mitoxantrone amongst
      many. Consolidation regimens using mainly alemtuzumab are also increasingly used
      but are associated with a major increase in severe infections. High-dose steroids
      in combination with rituximab or alemtuzumab represent a promising option for
      refractory patients. Modern chemoimmunotherapy with the FCR regimen has also been
      tested in early stage patients with unfavourable prognostic factors. Finally, a
      there are a wide variety of novel drugs including bendamustine, a unique
      cytostatic with combined properties of an alkylating agent and purine analog, the
      monoclonal antibodies anti-CD20 ofatumumab and the anti-CD23 lumiliximab,
      thalidomide and its analog lenalidomide, the semi-synthetic flavonoid
      flavopiridol and other agents which are currently undergoing clinical trials with
      promising results. This article reviews the recent advances and future
      possibilities in the treatment of CLL.

PMID- 19843379
TI  - Outpatient consolidation chemotherapy in pediatric acute myeloid leukemia: a
      retrospective analysis.
AB  - BACKGROUND: To assess the outcomes of outpatient high dose cytosine arabinoside
      consolidation cycles in pediatric acute myeloid leukemia (AML) patients in
      comparison to inpatient treatment. METHODS: We retrospectively analyzed 90 cycles
      of AML consolidation given to 30 patients between July 2003 and July 2007.
      RESULTS: Median age was 8 years (range 1.5-15) and 22/30 (73.3%) were males.
      Sixty-nine of 90 (76.7%) cycles were given on an ambulatory basis; readmission
      occurred in 25/69 (36.2%) and there was one death. The outpatient cycles in
      comparison to the inpatient cycles required significantly fewer invasive blood
      investigations (p<0.001) but had comparable number of blood products administered
      as supportive therapy. There was no significant difference in the frequency of
      granulocyte colony stimulating factor usage and recovery time of absolute
      neutrophil count and platelet count. The incidence of febrile neutropenia though
      was comparable in the groups (72.5% outpatient versus 76.2% inpatient), but the
      duration (p=0.003) and subsequent therapeutic antifungal usage (p=0.001) was
      significantly more in inpatient administered cycles. Second line antibiotics were
      needed in 16/50 (32%) outpatient episodes of febrile neutropenia in contrast to
      10/16 (72.5%) episodes of febrile neutropenia in inpatient courses (p=0.030).
      CONCLUSIONS: Outpatient AML consolidation therapy is safe and feasible in
      children. It appears to result in less frequent invasive blood studies; shorter
      duration of febrile neutropenia and consequently less antimicrobial and
      antifungal usage as compared to inpatient consolidation cycles. To our knowledge,
      this report is the first of its kind looking specifically at outpatient
      consolidation chemotherapy in AML.

PMID- 19843380
TI  - Molecular characterization of chronic myeloproliferative neoplasias in Mexico.
AB  - By using novel molecular markers, it is possible to gain information on both the
      classification and the pathophysiology of the chronic myeloproliferative
      neoplasia (MPN). In a group of 36 Mexican mestizo patients with MPN, we studied
      five molecular markers: The BCR/ABL1 fusion gene, the JAK2 V617F mutation, the
      JAK2 exon 12 mutations, the MPL W515L mutation and the MPL W515K mutation; 17
      patients with essential thrombocythemia (ET), eight with polycythemia vera (PV),
      four with primary mielofibrosis (MF), five with undifferentiated MPN, one with
      primary erythrocytosis and one with familial thrombocytosis. Patients with the
      BCR/ABL1 fusion gene were excluded. Twelve individuals with the JAK2 V617F
      mutation were found; 11 of them had been clinically classified as PV and one had
      been classified as MF. One patient with the MPL W515L was identified with a
      clinical picture of ET. No individuals with either the MPL W515K mutation or the
      JAK2 exon 12 mutations were identified. Of the 17 individuals with ET, six (35%)
      had the JAK2 V617F mutation and one (6%) was found to have the MPL W515L
      mutation. Of the eight individuals with PV, five displayed the JAK2 V617F
      mutation, whereas of the four patients with MF, one had the JAK2 V617F mutation.
      The most consistent relationship was that between PV and the JAK2 V617F mutation
      (p=0.08). In the diagnosis and classification of the MPN, in addition to the
      newly identified molecular markers, clinical and laboratory data are still very
      important.

PMID- 19843381
TI  - Relationship between expression of mutant type glutathione S-transferase theta-1
      gene and reactivity of rapamycin in myelodysplastic syndrome.
AB  - We previously reported mRNA expression of glutathione S-transferases theta (GSTT)
      1, wild type (623 bp) and mutant (500 bp), in patients with myelodysplastic
      syndrome (MDS). The deletion of 123 bp creates a sequence that is homologous to
      the mammalian target of rapamycin (mTOR). To analyze the function of mutant GSTT
      1 gene, stable transformants for the mutant and wild-type GSTT-1 gene,
      respectively, were established. In this study, the expression of the wild and
      mutant type of the GSTT-1 gene of those stable transformants in cell lines and in
      bone marrow cells from MDS patients by reverse-transcription polymerase chain
      reaction (RT-PCR) was observed in the presence or absence of rapamycin.
      Significant growth inhibition by rapamycin was observed among stable
      transformants for the mutant GSTT-1 gene, but not wild type GSTT-1 gene, and was
      indicative of typical apoptosis.

PMID- 19843382
TI  - Histiocytosis disorders in Northeast Egypt: epidemiology and survival studies (a
      5-year study).
AB  - Histiocytosis disorders include a wide group of disorders characterized by
      monocytes, macrophages and dendritic cell infiltration of different tissues.
      There are few clinico-epidemiologic studies of such disease. Our study was
      designed to look at the clinico-epidemiological features and outcome of patients
      with histiocytosis disorders in Northeast Egypt. Twenty-seven cases with
      histiocytosis disorders accrued over a 5-year period were analyzed and classified
      as having unifocal, multifocal, or multisystem disease. They were 14 males and 13
      females. Twenty-two patients representing 81.5% of cases were more than two years
      of age while 5 patients (18.5%) were less than 2 years. Lymphadenopathy was the
      commonest presentation (55.55%) followed by bone lesions (44.44%). Involvement
      was unifocal in 12, multifocal in 10, and multisystem in 5 cases. The
      histological features were relatively uniform regardless of the clinical
      severity, and consisted of Langerhans cells, eosinophils, histiocytes, plasma
      cells, giant cells and fibrosis. The treatment consisted of a combination of
      surgery, chemotherapy, and/or radiotherapy. Lymphadenopathy was the most common
      clinical presentation in our locality. Response to treatment was poor in patients
      with multisystem disease. Patients with age less than 2 years were more likely to
      have increased risk of morbidity and mortality, due to widespread disease.

PMID- 19843383
TI  - Antiplatelet antibodies contribute to thrombocytopenia associated with chronic
      hepatitis C virus infection.
AB  - Thrombocytopenia is one of the most frequent hematological manifestations of
      hepatitis C virus (HCV) infection; which typically worsens with progression of
      the liver disease and can become a major clinical complication. Several
      mechanisms have been postulated to explain thrombocytopenia in HCV hepatic
      patients, including immune mechanisms. The aim of the present work is to
      investigate the role of immune mechanisms as a causative agent of
      thrombocytopenia in HCV hepatic patients. The study included 50 hepatic patients
      with HCV infection (30 with thrombocytopenia and 20 with normal platelets
      counts). Platelets associated glycoprotein specific antibodies were evaluated by
      flow cytometry and confirmed by quantitative monoclonal immobilization of
      platelet antibodies (MAIPA). The frequency of platelet associated immunoglobulin
      (PAIg) in thrombocytopenic HCV positive hepatic patients by FCM was 86.7, 83.3,
      46.7 and 33.3% for total PAIg, PAIgG, PAIgM and PAIgA respectively. MAIPA found
      platelet specific antibodies in 26/30 (86.7%) of patients. The most likely target
      antigen for platelets antibodies were glycoprotein (GP) IIb/IIIa (30%), followed
      by GP IIIa (20.5), GP IIb (13.3%), GPIb (13.3%), then GPIa (10%). The platelets
      count was inversely correlated to the levels of platelets GP specific antibodies
      (r=-0.42, p=0.024), and significantly parallel to spleen size (p=0.024). Platelet
      associated glycoprotein specific antibodies represent a common mechanism inducing
      thrombocytopenia in patients with chronic HCV infections.

PMID- 19843384
TI  - Effect of Helicobacter pylori eradication on platelet count in children with
      chronic idiopathic thrombocytopenic purpura.
AB  - Recent reports have suggested, particularly in adults, an association between
      Helicobacter pylori infection (HPI) and chronic idiopatic thrombocytopenic
      purpura (cITP) with improvement of platelet count after eradication therapy. We
      investigated the association of HPI and cITP and the effect of HP eradication
      therapy on thrombocytopenia in a population of 24 children of both sexes mean age
      8.0+/-0.28 years (range 5.4-10.7 years), affected by cITP (PLT <or=50 x 10(9)/l)
      lasting more than 6 months. HPI was investigated by Helicobacter pylori stool
      antigens (HpSA). In eight out 24 patients (33.3%) HP infection was identified
      positive and bacterial eradication was successful following 7 days of triple
      therapy (amoxicillin, clarithromicin and proton pump inibitors). A follow-up of
      platelet count was performed for 1 year after HpSA detection. Six out eight
      patients (75%) had total recovery of platelet count during the first year after
      bacterial eradication (PLT before therapy 32.5+/-3.5 x 10(9)/l; after 1 year
      275+/-106.06 x 10(9)/l) (P<0.05), two patients (25%) had partial recovery (PLT
      before therapy 30 x 10(9)/l, after 1 year 103.5 x 10(9)/l) although not reaching
      statistical significance (P>0.05). Non-significant differences were found in
      platelet count between infected and uninfected patients before eradication
      treatment (PLT 33.0+/-2.8 x 10(9)/l versus 34.0+/-5.75 x 10(9)/l) (P>0.05), while
      significant differences were observed after eradication therapy (PLT 315.0+/-7.07
      x 10(9)/l versus 43.5+/-2.12 x 10(9)/l) (P<0.05). HP assessment should be
      performed in all cITP patients and eradication therapy should be attempted in
      positive cases.

PMID- 19843385
TI  - A retrospective analysis of therapeutic responses to two distinct corticosteroids
      in 259 children with acute primary idiopathic thrombocytopenic purpura.
AB  - OBJECTIVE: To analyze the responses of pediatric patients with newly-diagnosed
      acute primary idiopathic thrombocytopenic purpura (ITP) to two distinct
      corticosteroids. METHODS: We retrospectively reviewed a cohort of 259 patients
      with acute ITP diagnosed between 2004 and 2008. Specifically, we compared
      response rates and adverse effects in patients treated with methylprednisolone or
      dexamethasone. RESULTS: Corticosteroids were used as the first-line treatment in
      all patients with an initial response rate of 96.5%. Choice of the intravenous
      corticosteroid for treatment did not affect the outcome of patients. The time
      platelet count maintained at a normal level showed no statistical difference
      between patients administered with methylprednisolone or dexamethasone. Only
      minor adverse effects were observed in both groups of patients. CONCLUSIONS: Both
      corticosteroids yielded similarly high response rates and minor adverse effects
      in ITP patients. This should be taken into account when choosing the treatment
      regimen for children with acute ITP.

PMID- 19843386
TI  - Molecular variants and clinical importance of beta-thalassaemia traits found in
      the state of Orissa, India.
AB  - Prevention of beta thalassaemia implies knowledge of the molecular spectrum
      occurring in the population at risk. This knowledge is necessary, especially when
      a prevention protocol is applied to a multiethnic population. For this purpose,
      we carried out molecular analysis of 431 beta thalassaemia subjects belonging to
      tribal (aboriginal) and non-tribal communities of Orissa, a part of peninsular
      India and found six types of mutation (four previously unreported and two
      reported). Molecular analysis of beta gene mutation showed that out of 431 beta
      thalassaemia cases (265 beta thalassaemia traits, 64 beta thalassaemia major, 47
      haemoglobin E-beta thalassaemia, 55 haemoglobin S-beta thalassaemia cases), 71%
      of cases (n=306) showed the IVS I-5(G-->C) mutation, 12% of cases (n=52) showed
      FS 41/42(-CTTT), 7% of cases (n=30) showed CD 15(G-->A), 4.8% of cases (n=21)
      showed CD 30 (G-->C), 3% of cases (n=13) showed FS 8/9 (+G), and 2% of cases
      (n=9) showed IVSI-1(G-->T). The tribal populations possess only the IVS I-5(G-
      >C) mutation whereas the non-tribal groups possess the FS 41/42(-CTTT), FS 8/9
      (+G), IVS I-1(G-->T), CD30(G-->C) and IVS I-5(G-->C) mutations. Among the non
      tribal communities, Muslims did not have the IVS I-1 (G-->T) mutation.
      Clinically, anaemia was mild to moderate in beta thalassaemia trait and was found
      to be associated with the majority of abnormalities such as pyrexial episodes,
      fatigue, headache, lethargy and pallor. However, there were no differences in the
      incidence of clinical abnormalities between tribal and non-tribal populations and
      also among the different molecular variants of beta gene. This is the first
      report from Orissa on the prevalence of different molecular variants of beta
      thalassaemia. The clinical presentation of beta thalassaemia trait cases and
      their variation from other population have been discussed with reference to the
      different genetic variants.

PMID- 19843387
TI  - Alpha globin gene numbers: an important modifier of HbE/beta thalassemia.
AB  - HbE [beta 26 Glu-Lys] is the second most common abnormal Hb in humans. HbE when
      associated with beta thalassemia (HbE/beta thalassemia) in compound heterozygous
      state results in a clinically severe condition. HbE/beta thalassemia has a very
      variable clinical phenotype. One of the possible explanations for the observed
      variable clinical severity is variation of alpha gene number. The main aims of
      this study were to determine the frequency of alpha deletion/mutations and
      triplication in HbE/beta thalassemia patients and to study the effect of alpha
      gene numbers on the phenotype of these patients. 240 HbE/beta thalassemia
      patients who attended the Hematology Outpatient Department of the Institute were
      studied. Patients were divided into three groups mild (score=0-3.5), moderate
      (score=4-7) and severe (score=7.5-10). alpha deletion was found in 22 (7.5%), out
      of these 22 patients 16 (11 alphaalpha/-alpha(3.7), 4-alpha(3.7)/-alpha(3.7) & 1
      alphaalpha/--(SA)) were from Gp I and 6 (alphaalpha/-alpha(3.7)) were from Gp II.
      alpha triplication was found in 7 (2.9%) and out of these 7 patients 5 were
      (alphaalpha/alphaalphaalpha(anti-3.7)) from Gp III and 2 were
      (alphaalpha/alphaalphaalpha(anti-3.7)) from Gp II. The most common interaction
      was found to be HbE/beta thalassemia and deletional alpha(+)-thalassemia
      (alphaalpha/-alpha(3.7)) followed by others. alpha deletions and point mutations
      genotype were mostly observed in the individuals from Gp I while alpha
      triplication was most frequent in Gp III individuals. Interaction of HbE/beta
      thal with alpha-thalassemia is common in the Indian population. Patients
      inheriting alpha deletions and point mutations behaved mildly with some
      exceptions, while patients with alpha triplication had a severe phenotype
      requiring frequent transfusions.

PMID- 19843388
TI  - Pregnancy in beta-thalassemia trait carriers: an uneventful journey.
AB  - Normochromic normocytic anemia during pregnancy reflects the significant increase
      in plasma volume, which disproportionately exceeds the increase in the red cell
      volume. In beta-thalassemia (beta-thal) trait carriers who become pregnant the
      plasma volume expansion may cause more pronounced anemia because the anemia of
      pregnancy is added to the pre-existed hypochromic microcytic anemia. In beta-thal
      women, pregnancy outcome and obstetric complications do not differ from the
      general population. Anemia in beta-thal carriers is generally not severe enough
      to warrant anxiety. No specific therapy is indicated and pregnant women generally
      require only supportive care with an anticipated favorable pregnancy outcome.

PMID- 19843389
TI  - Red blood cell flags for the differential diagnosis between thalassemia trait and
      iron deficiency anemia.

PMID- 19843390
TI  - Evaluation of an immunoturbidimetric D-dimer assay and pretest probability score
      for suspected venous thromboembolism in a district hospital setting.
AB  - Venous thromboembolism is a leading cause of co-morbidity and death in hospital
      patients. This observational study looks at the usefulness of pretest probability
      and immunoturbidimetric D-dimer levels for the diagnosis of thromboembolic
      episodes in outpatients (108 of 197; 54.8%) and inpatients (89 of 197; 45.2%).
      Across 197 consecutive patients, D-dimers showed 100% sensitivity (95% CI, 87
      100%). As a result, the combination of normal D-dimers and low or intermediate
      probability score yielded a negative predictive value of 100% (95% CI, 90.6
      100%). The tests lacked specificity and positive predictive value. Normal D-dimer
      level in patients with low or intermediate pretest probability makes venous
      thromboembolism an unlikely diagnosis and may obviate the need for confirmatory
      scans. All other patients will need diagnostic imaging. Clinicians should be
      aware of the above utility and limitations while making management decisions for
      patients with suspected thromboembolism.

PMID- 19843391
TI  - A decade of ivermectin-albendazole donation for lymphatic filariasis.

PMID- 19843392
TI  - Ten years of managing the clinical manifestations and disabilities of lymphatic
      filariasis.
AB  - The aim of the Global Programme to Eliminate Lymphatic Filariasis is to eradicate
      one of the world's leading causes of permanent and long-term disability, at least
      as a public-health problem. The achievement of this goal is based on the
      interruption of the transmission of the causative parasites (so preventing new
      cases) and, as a 'second pillar', the prevention of disability in those who are
      infected. The disability is associated with the main clinical manifestations of
      human infection with Wuchereria or Brugia spp. (i.e. hydrocele, lymphoedema
      and/or 'acute attacks'). The World Health Organization and its partners have
      established strategies and activities both for managing lymphoedema, through
      community home-based care, and for increasing access to surgery for hydrocele.
      Over the last decade, there has been progress made in preventing the disability
      of lymphatic filariasis, the monitoring and evaluation of such disability and its
      control, and the integration of disability prevention with mass drug
      administrations and efforts to control other disabling diseases. That progress
      and the challenges that remain in the prevention of the morbidity and disability
      attributable to lymphatic filariasis are here reviewed.

PMID- 19843393
TI  - GlaxoSmithKline and Merck: private-sector collaboration for the elimination of
      lymphatic filariasis.
AB  - More than 1000 million people in 82 countries are at risk of contracting the
      tropical disease lymphatic filariasis (LF). Although the disease is wide-spread,
      transmission of the causative parasites can be stopped through mass drug
      administrations based on a combination of anti-parasitic medicines. For more than
      10 years, the pharmaceutical companies GlaxoSmithKline (GSK) and Merck & Co.,
      Inc., have participated in a unique private-sector collaboration to support the
      global efforts to eliminate LF, through donations of drugs to prevent the
      disease. GSK's albendazole and Merck's ivermectin (Mectizan) now reach hundreds
      of millions of people each year, through national LF-elimination programmes
      carried out in collaboration with Ministries of Health, the World Health
      Organization, non-governmental organizations and local communities. Working in
      support of the Global Programme to Eliminate Lymphatic Filariasis, GSK and Merck
      not only provide donated medicines but also offer financial, programmatic and
      management expertise to support LF-elimination efforts worldwide.

PMID- 19843394
TI  - The Global Programme to Eliminate Lymphatic Filariasis: health impact during its
      first 8 years (2000-2007).
AB  - During its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis
      provided more than 1900 million treatments with antifilarial drugs (albendazole,
      ivermectin and diethylcarbamazine) to at least 570 million people in 48 countries
      with endemic lymphatic filariasis (LF). As a result of this impressive global
      effort and an unprecedented public-private partnership, 8 years of mass drug
      administration (MDA) have prevented the spread of filarial infection to an
      estimated 6.6 million newborns, stopped the progression to clinical morbidity in
      9.5 million individuals already infected with the parasites that cause LF, and
      drastically reduced the burden of several co-infections. The resulting health
      benefits of the MDA, in terms of reduced morbidity and disability-adjusted life
      years, are thus enormous. The next step should be an analysis of the Global
      Programme's economic impact from its first 8 years of MDA.

PMID- 19843395
TI  - Challenges for the integration of mass drug administrations against multiple
      'neglected tropical diseases'.
AB  - Simple and safe medications for some of the common, but often neglected, diseases
      that afflict the poor are not only available but are often donated. Other
      medications indicated for neglected diseases are extremely cheap and cost
      effective. These drugs can be administered together and combined, when feasible,
      into rapid-intervention packages based on mass drug administrations. It is
      therefore logical to integrate mass drug administrations when possible.
      Integration is, however, not always as simple as it seems, and 'integration'
      means different things to different people. Drugs are needed at different
      frequencies for different lengths of time, sometimes for the whole population,
      sometimes only for children. Care has to be taken that parallel systems are not
      created that bypass primary healthcare. Much can be achieved, however, by
      sensible integration, whether it be in the mapping of diseases or the setting up
      of treatment platforms that tackle several diseases at once. As governments and
      international organizations seek to create policies for integration that include
      not only mass drug administration but also morbidity control, and as various
      partnerships develop for implementation, there is the possibility to scale up
      health interventions, which will have a very positive impact on the poorest
      communities globally. Nevertheless, integration should not be forced for the sake
      of policy. Where things fit well they should be developed, where not,
      coordination within the primary-healthcare system can produce an equally long
      lasting impact.

PMID- 19843396
TI  - The development of albendazole for lymphatic filariasis.
AB  - The history of the development of ivermectin and diethylcarbamazine for the
      treatment of human filarial infections is relatively well known and documented.
      The story of how albendazole became involved in the global elimination programmes
      is, however, less well known. This review examines the thinking and the processes
      behind the development of albendazole, from the first ideas in the mid 1980s to
      the establishment of the Global Programme to Eliminate Lymphatic Filariasis.
      Throughout, the approaches were essentially different from those of traditional
      drug development and, in the end, there was a recommendation for a particular
      public-health use that was not formally approved by the regulatory authorities.
      While there is no doubt about the efficacy of albendazole for the treatment of
      many helminth diseases, as a single agent it could never be recommended for
      filariasis.

PMID- 19843397
TI  - Lymphatic filariasis: patients and the global elimination programme.
AB  - The defining images of lymphatic filariasis are the horrendous disfigurements of
      lymphoedema, elephantiasis and hydrocele. These clinical presentations, although
      obviously important and life changing, are not, however, the only outcomes of
      this wide-spread filarial infection. The other effects of the disease range from
      severe, acute but short-term bouts of sickness to psychological impairment,
      poverty and family hardship. It is important to support cases of the disease
      through all means available, such as reparative hydrocelectomy, hygiene training
      and facilitation, and the provision of adequate chemotherapy. Although only a
      minority of the residents in any endemic community is affected with the severe
      clinical manifestations of this parasitic infection, these cases are central to,
      and important advocates for, the current global effort to eliminate the infection
      through mass drug administrations (MDA). Their clinical improvement acts as an
      important catalyst for the general population and encourages high compliance in
      the MDA. This communication discusses the central role that filariasis patients
      have played in the Tanzania Lymphatic Filariasis Elimination Programme to date,
      and covers some of the clinical successes achieved in the past 10 years. The
      abolition of the clinical manifestations of filarial infection remains the
      ultimate goal of the Global Programme to Eliminate Lymphatic Filariasis, and
      maintaining a focus on the affected individuals and their clinical condition is
      vital to that programme's overall success.

PMID- 19843398
TI  - The sharp end - experiences from the Tanzanian programme for the elimination of
      lymphatic filariasis: notes from the end of the road.
AB  - The Tanzania Lymphatic Filariasis Programme, which was launched in 2000, is, in
      terms of geographical coverage, among the largest disease-control programmes in
      Tanzania's history, currently reaching 9.4 million people in 34 districts. The
      issues associated with this programme's implementation are reviewed here, in the
      context of the various players/stakeholders involved. This article provides an
      insight of how the programme began and discusses key areas in the programme's
      design. Mainly, however, it gives some impressions of how the programme is
      perceived by, and how it affects, village healthworkers, patients and politicians
      - the people who contribute to the implementation of the programme at various
      levels.

PMID- 19843399
TI  - Allergic rhinitis with negative skin tests: does it exist?
AB  - Nonallergic rhinitis (NAR) is a common disorder encountered by the practicing
      allergist/immunologist. The immunopathology of allergic rhinitis (AR) and NAR
      share several characteristics. Patients with AR have allergen-specific IgE
      demonstrable both systemically (e.g., positive skin tests) as well as local IgE
      produced in the nasal mucosa. A few studies have evaluated patients with NAR
      using nasal provocation with allergen. Some, but not all, studies have revealed
      positive allergen challenge in these nonallergic subjects with negative skin
      tests. This article reviews these studies and highlights the differences in
      methodology. Further refinements and standardization of nasal provocation
      techniques may be required before proving that localized IgE-mediated allergy
      occurs in patients with negative skin tests.

PMID- 19843400
TI  - Allergic rhinitis, histamine, and otitis media.
AB  - Otitis media (OM) is a common and costly medical condition, especially in
      children. Most episodes of OM are associated with an upper respiratory viral
      infection and are short-lived and self-limiting with or without medical
      treatment. However, chronic OM with effusion (OME) has significant sequelae, is
      refractory to most medical treatments, and frequently requires surgical
      intervention. The pathophysiology of OME is complex and involves both eustachian
      tube (ET) dysfunction and middle ear pressure dysregulation. OM likely results
      from an increase in blood flow to and, thus, gas loss from the middle ear, in
      combination with a dysfunctional ET that can not resupply that gas. These
      processes could be induced by viral and/or allergen-driven inflammation. A large
      body of epidemiologic and mechanistic evidence supports a role for allergic
      rhinitis as a risk for OM. Indeed, evidence also supports a role for histamine in
      both conditions. However, not all such evidence is supportive of this
      relationship and a causal relationship between the two conditions has not been
      definitively proven. Moreover, therapeutic trials using common allergy therapies
      have either not been conducted or showed no benefit in OM. This prompted the 2004
      clinical practice guidelines on OM to conclude that no recommendations could be
      made for "... allergy management as a treatment for OME based on insufficient
      evidence of therapeutic efficacy or a causal relationship between allergy and
      OME." Nonetheless, given the strong likelihood of allergy as a risk factor for
      OM, allergic rhinitis patients should be evaluated for OM and patients with OME
      should be considered for an allergy evaluation. If significant allergic rhinitis
      is diagnosed in a patient with OME, it should be treated aggressively (as in any
      case of moderate to severe allergic rhinitis) until further studies are
      conducted. No definitive conclusions about a role for food allergy in causing or
      treating OM can be made. Clearly, more studies are needed to examine the
      relationship between these two important conditions.

PMID- 19843401
TI  - Histamine, antihistamines, and the central nervous system.
AB  - Histamine is a central nervous system (CNS) neurotransmitter. It acts in the
      brain via three receptors, H(1), H(2), and H(3). It is a mediator of
      "wakefulness" and its activity is necessary to maintain wakefulness, alertness,
      and reaction time. These activities can be impaired by H(1)-antagonists (reverse
      agonists) capable of penetrating the blood-brain barrier. By blocking the
      homeostatic effects of histamine in the CNS, drowsiness and functional impairment
      with or without drowsiness can occur. Several tests have been designed to assess
      the effects of antihistamines on the CNS. These include subjective measurements
      of drowsiness and more objective measurements of impairment. Second-generation
      antihistamines have been designed to minimize blood-brain barrier penetration by
      reducing lipophilicity and increasing the affinity for P-aminnoglycoprotein.

PMID- 19843402
TI  - Pathogenesis and laboratory diagnosis of hereditary angioedema.
AB  - Hereditary angioedema (HAE) was first described in the 19th century. Over the
      past 50 years, many details of the pathophysiology and molecular biology of HAE
      have been elucidated. Two types of HAE, type I and type II, result from mutations
      in the gene for the broad-spectrum protease inhibitor C1 inhibitor (C1INH). Type
      I HAE is characterized by low antigenic and functional C1INH levels and type II
      HAE has normal antigenic but low functional C1INH levels. Type III HAE, by
      contrast, has normal antigenic and functional C1INH levels. In some families,
      type III HAE has been linked to mutations in Hageman factor. C1INH is the primary
      inhibitor of the complement proteases C1r and C1s as well as the contact system
      proteases activated Hageman factor (coagulation factor XIIa and XIIf) and plasma
      kallikrein. It is also an inhibitor of plasmin and coagulation factor XIa. The
      primary mediator of swelling in HAE has now been unequivocally shown to be
      bradykinin, generated from activation of the plasma contact system. The knowledge
      gained concerning the underlying mechanisms of the different types of HAE allow
      the clinician to approach the laboratory diagnosis with confidence and provides
      opportunities for novel therapeutic strategies.

PMID- 19843403
TI  - Variability of prodromal signs and symptoms associated with hereditary angioedema
      attacks: a literature review.
AB  - Hereditary angioedema (HAE) is a rare disease caused by deficiency in the
      production or function of C1 inhibitor. It predisposes individuals to paroxysmal
      acute attacks causing painful, debilitating, disfiguring, and life-threatening
      angioedema. Prodromes occurring hours to days before attacks have been described
      in the literature; however, their significance as predictive signals of impending
      attacks is uncertain. Given the morbidity and mortality associated with HAE
      attacks and the increasing availability of therapeutic products for their
      treatment, identifying prodromes that accurately predict the onset of attacks
      could provide the basis for the development of a validated instrument to identify
      the onset of such attacks requiring abortive therapeutic intervention before the
      development of clinically significant angioedema. The aim of this study was to
      review the literature to identify the prodromes reported to occur with HAE
      attacks. A literature review of English language journal articles was performed
      using search terms hereditary angioedema, HAE, angioneurotic edema, prodrome,
      signs, and symptoms. Nineteen original English language articles that included
      both case reports and studies describing prodromes associated with HAE attacks
      were obtained. Our review indicates that there is significant variability in the
      expression, manifestation, prevalence, timing, and predictive reliability of the
      prodromes that have been described. There is considerable variability of the
      prodromal manifestations that may occur before or during HAE attacks. We have not
      found any evidence that their sensitivity and specificity for accurately
      predicting such attacks has been studied.

PMID- 19843404
TI  - Update on therapeutic developments for hereditary angioedema.
AB  - Remarkable progress has been made in understanding the molecular mechanisms
      underlying attacks of swelling in hereditary angioedema (HAE). Treatment options
      in the United States for this potentially life-threatening disease had remained
      essentially static, however, over the past 40 years. Prophylactic therapy had
      relied on attenuated androgens or antifibrinolytic agents. Although demonstrably
      effective, these drugs have been fraught with side effects. Acute therapy has
      been largely relegated to supportive care. In this article we discuss emerging
      treatments that have evolved from the recognition that kinin generation is the
      fundamental abnormality leading to attacks of angioedema. We will review the
      newly approved replacement therapy for prophylaxis of HAE attacks with C1
      inhibitor (C1INH). Potential options for the acute treatment of HAE will be
      discussed including purified C1INH, recombinant C1INH, an inhibitor of plasma
      kallikrein, and a B2-receptor antagonist. The arrival of these novel therapies
      promises to transform the future management of HAE.

PMID- 19843405
TI  - Frequency, timing, and type of prodromal symptoms associated with hereditary
      angioedema attacks.
AB  - Hereditary angioedema (HAE) types I and II are autosomal dominant conditions
      characterized by recurrent attacks of edema formation in the subcutaneous tissue
      of the body or walls of the upper respiratory or gastrointestinal tract.
      Frequently, prodromal symptoms occur before an HAE attack. If certain prodromal
      symptoms were determined to be both sensitive and specific in predicting an acute
      HAE attack, treatment at the time of the prodrome could prevent development of an
      attack and decrease morbidity and mortality associated with HAE. The goal is to
      determine the frequency and timing of prodromal symptoms occurring before HAE
      attacks. After Institutional Review Board approval, a four-page survey was
      produced, using a focus group of patients with HAE and was assessed by HAE
      patients and physicians with expertise in HAE for cognitive reliability. Once
      devised, the questionnaire was sent to 158 HAE patients. The survey focused on
      questions related to prodromal symptoms that patients developed before their last
      HAE attack. Forty-six patients returned the survey and 40 (87.0%) reported the
      presence of prodromal symptoms before their last HAE attack. Forty-four of 46
      (95.7%) reported having had prodromal symptoms before HAE attacks in the past.
      The most commonly reported prodromal symptoms included unusual fatigue, rash, and
      muscle aches. Prodromes occur frequently before HAE attacks. This high frequency
      suggests that prodromal symptoms could be a reliable indication to begin
      treatment to prevent an acute HAE attack, thus decreasing the anxiety associated
      with having an HAE attack.

PMID- 19843406
TI  - Patients' and primary care physicians' beliefs about asthma control and risk.
AB  - Patients' and physicians' knowledge of asthma control and risks can affect long
      term outcomes. The Asthma General Awareness and Perceptions II (Asthma GAP II)
      survey sought to assess the beliefs and behaviors of asthma patients and their
      physicians. In the United States, a telephone survey was conducted among 1885
      adults with asthma (representative population sample [n = 1001] plus additional
      black [n = 436] and Hispanic samples [n = 448]) who took asthma medication in the
      previous year. An online survey included 300 primary care physicians. Most
      patients (66, 84, and 78% of national, black, and Hispanic samples, respectively)
      and physicians (80%) considered asthma a very or extremely serious condition. In
      contrast to current guidelines, most patients (69, 72, and 70%) believed that
      quick-relief medications could be taken daily. Many patients (42, 52, and 60%)
      and some physicians (22%) stated controller medications could be taken less
      regularly when symptoms decrease, although most patients (92, 92, and 89%) and
      physicians (95%) indicated that controller medications are most effective when
      taken daily. Of patients who discontinued controller medications (21%), 71%
      discontinued when symptoms abated. Most physicians (87%) believed that patients
      discontinued controller medications without their advice. After controller
      medication cessation, more black (22%) and Hispanic patients (22%) than patients
      in the national sample (15%) experienced serious health consequences after an
      asthma attack. Gaps exist between patients' understanding of asthma control and
      their use of controller and quick-relief medications. Many patients and
      physicians fail to recognize that, even with symptom abatement, serious asthma
      risks remain.

PMID- 19843407
TI  - Debilitating beliefs and emotional distress in patients given immunotherapy for
      insect sting allergy: a prospective study.
AB  - Patients who receive venom immunotherapy (VIT) for systemic reactions (SRs) to
      insect stings are advised that once they reach the maintenance dose they are
      almost 100% protected against future SRs. However, initial evidence indicates
      that some patients continue to perceive themselves as highly debilitated by the
      allergy and are preoccupied with the allergic event. These factors have
      significant impact on their emotional well-being and allergy-related quality of
      life (ARQOL). We aimed to explore prospectively whether patients would experience
      these adverse psychological outcomes after receiving VIT coupled with
      professional explanation and reassurance of protection. Thirty-four patients who
      received VIT for systemic insect allergy and were under close medical
      surveillance were included. Before and 1 year after initiation of treatment,
      patients completed a questionnaire that measured debilitating beliefs,
      preoccupation with the SR event, emotional distress ARQOL, and QOL in general.
      Physician-graded severity of the reaction was recorded as well. VIT had a
      beneficial effect on all allergy-related variables. Self-imposed debilitating
      beliefs, preoccupation with the anaphylactic event, and ARQOL significantly but
      modestly improved over time. No association was found between ARQOL and QOL in
      general. The later variable as well as emotional distress remained unchanged
      after the VIT. This study shows that patients with sting allergy guided by
      trained personnel and treated with VIT show a reduction in dysfunctional beliefs
      and an improvement in ARQOL. Disputing medically unfounded beliefs that persist
      in some patients might improve their ARQOL.

PMID- 19843408
TI  - Serum levels of protein oxidation products in patients with nickel allergy.
AB  - Nickel sensitization can not only induce allergic contact dermatitis (ACD), but
      also can induce an overlapping disease referred to as "systemic nickel allergy
      syndrome" (SNAS), characterized by urticaria/angioedema and gastrointestinal
      symptoms correlated to the ingestion of nickel-containing foods. This study was
      designed to determine if oxidative stress occurs in patients with nickel allergy.
      Thirty-one female patients (mean age 31.26 + 13.04 years, range 16-64 years) with
      confirmed nickel CD underwent oral nickel challenge because of clinically
      suspected SNAS; serum concentrations of protein carbonyl groups (PCGs) and
      nitrosylated proteins (NPs; biomarkers of oxidative stress) were measured before
      and after oral nickel challenge as well as in healthy female controls. Twenty
      three of these 31 patients were diagnosed with SNAS because they had a positive
      reaction to the oral nickel challenge, and 8 patients had no reaction and
      therefore were classified as patients with contact nickel allergy only. Although
      both nickel-allergic patients and controls presented similar serum levels of
      PCGs, NP values in nickel-allergic patients appeared higher than in controls and
      tended to decrease after the challenge; furthermore, serum levels of NPs in
      patients affected by SNAS were higher (although not significantly) than in
      patients with nickel ACD only. The involvement of specific biomarkers of
      oxidative stress such as NPs and the lack of involvement of other biomarkers such
      as PCGs may help to better understand the alteration of the redox homeostasis
      occurring in nickel ACD and particularly in SNAS.

PMID- 19843409
TI  - Twenty-one year old woman with severe eosinophilia and left bundle branch block.
AB  - Peripheral and tissue eosinophilia can occur in a wide variety of disease
      processes that include infectious, allergic, and primary hematologic disorders,
      and other more rare diseases such as hypereosinophilic syndromes (HES). We
      describe a case of a patient with severe eosinophilia and left bundle branch
      block. A 21-year-old woman with asthma and allergic rhinitis presented with neck
      pain and cough for >6 months with no other complaints. Physical exam was normal
      except for fever and minimal expiratory wheezes. Chest CT revealed diffuse airway
      inflammation with bronchiectasis. Admission electrocardiogram (EKG) was normal.
      Initial laboratory tests showed an absolute eosinophil count of 30,000 cells/mL.
      A thorough workup for eosinophilia was initiated, but the patient subsequently
      left against medical advice. The next day, in the outpatient pulmonary clinic,
      she was found to be tachycardic and an EKG showed sinus tachycardia with a new
      left bundle branch block. Laboratory tests revealed an eosinophil count of 33,200
      cells/mL and elevated troponins. She was started on i.v. Solu-Medrol (Pfizer,
      Inc.). The next day, her EKG returned to normal. Three days later her absolute
      eosinophil count normalized. Identifying the cause of marked, persistent
      eosinophilia is a challenging problem. Excluding the more common causes of severe
      eosinophilia is required before making a diagnosis of HES and early therapeutic
      intervention can prevent morbidity from the disease.

PMID- 19843410
TI  - Solar urticaria.
AB  - A case of solar urticaria is presented, followed by a discussion of the clinical
      characteristics, pathophysiology, diagnosis, and management of this disease.
      Special emphasis is given to clinical pearls and pitfalls for the practicing
      allergist. Solar urticaria is a physical urticaria that can be difficult to
      diagnose and distinguish from other photodermatoses. There are some
      characteristic features that are important to remember when evaluating a patient
      with suspected solar urticaria. Testing can be difficult without the assistance
      of an experienced dermatologist because there are several different wavelengths
      of light that can lead to a patient's symptoms. Solar urticaria tends to be a
      chronic disease with a low 5-year resolution rate but can usually be effectively
      managed with multiple antihistamines.

PMID- 19843411
TI  - Which practices are high antibiotic prescribers? A cross-sectional analysis.
AB  - BACKGROUND: Substantial variation in antibiotic prescribing rates between general
      practices persists, but remains unexplained at national level. AIM: To establish
      the degree of variation in antibiotic prescribing between practices in England
      and identify the characteristics of practices that prescribe higher volumes of
      antibiotics. DESIGN OF STUDY: Cross-sectional study. SETTING: 8057 general
      practices in England. METHOD: A dataset was constructed containing data on
      standardised antibiotic prescribing volumes, practice characteristics, patient
      morbidity, ethnicity, social deprivation, and Quality and Outcomes Framework
      achievement (2004-2005). Data were analysed using multiple regression modelling.
      RESULTS: There was a twofold difference in standardised antibiotic prescribing
      volumes between practices in the 10th and 90th centiles of the sample (0.48
      versus 0.95 antibiotic prescriptions per antibiotic STAR-PU [Specific Therapeutic
      group Age-sex weightings-Related Prescribing Unit]). A regression model
      containing nine variables explained 17.2% of the variance in antibiotic
      prescribing. Practice location in the north of England was the strongest
      predictor of high antibiotic prescribing. Practices serving populations with
      greater morbidity and a higher proportion of white patients prescribed more
      antibiotics, as did practices with shorter appointments, non-training practices,
      and practices with higher proportions of GPs who were male, >45 years of age, and
      qualified outside the UK. CONCLUSION: Practice and practice population
      characteristics explained about one-sixth of the variation in antibiotic
      prescribing nationally. Consultation-level and qualitative studies are needed to
      help further explain these findings and improve our understanding of this
      variation.

PMID- 19843412
TI  - Reduced antibiotic prescribing for acute respiratory infections in adults and
      children.
AB  - BACKGROUND: Recent public health efforts, including in the UK and US, have
      targeted decreasing unnecessary antibiotic use. In the US, prescribing for acute
      non-specific respiratory infections (ARIs) has decreased, but broad-spectrum
      antibacterial prescribing has soared. AIM: To assess recent trends in
      antibacterial prescribing for ARIs in the UK. DESIGN OF STUDY: Retrospective
      cohort. SETTING: The Health Improvement Network database. METHOD: Outpatient ARI
      visits from 1 January 1990 to 31 December 2004 were selected. Outcomes were
      antibacterial and broad-spectrum antibacterial prescriptions per thousand person
      years, and the probability of receiving an antibacterial and broad-spectrum
      prescription conditional on an ARI visit. RESULTS: From 1990 to 2004,
      antibacterial prescribing rates for ARIs decreased from 55.0 to 30.3
      prescriptions/1000 person-years for adults and from 124.8 to 46.3
      prescriptions/1000 person-years for children (P=0.001). The probability of
      receiving an antibacterial prescription after an ARI visit decreased from 70.8%
      to 59.5% for adults and from 46.1% to 30.8% for children (P=0.003 and 0.007,
      respectively). Antibacterial prescribing declined faster for younger than for
      older adults. Broad-spectrum antibacterial prescribing rates decreased from 3.8
      to 2.9 prescriptions/1000 person-years for adults and from 5.2 to 2.2
      prescriptions/1000 person years for children (P=0.005 and 0.003, respectively).
      The probability of broad-spectrum prescribing did not demonstrate a significant
      linear trend for adults (P=0.16), and decreased for children (P=0.01).
      CONCLUSION: UK antibacterial prescribing for ARIs has declined, similar to US
      trends, but there was no concomitant increase in low broad-spectrum prescribing.
      The success of UK strategies for limiting antimicrobial use has implications for
      programmes in other countries.

PMID- 19843413
TI  - Identification of new risk factors for pneumonia: population-based case-control
      study.
AB  - BACKGROUND: Certain conditions are established as risk factors for community
      acquired pneumonia. There are a number of other conditions that may also be risk
      factors, but information on these is limited. AIM: To determine new independent
      risk factors for community-acquired pneumonia using a very large primary care
      database. DESIGN OF STUDY: Nested case-control study. SETTING: Four hundred and
      forty-three general practices in the UK contributing to the QRESEARCH database.
      METHOD: A total of 17 172 incident cases of all ages diagnosed with pneumonia
      between 1996 and 2005 were matched with up to five controls by age, sex, general
      practice, and calendar year. Associations between pneumonia and each established
      condition and potential risk factors were determined with odds ratios (ORs),
      using multiple conditional logistic regression analysis adjusted for smoking,
      socioeconomic status, and use of influenza and pneumococcal vaccines. RESULTS:
      The analysis confirmed the higher risk of pneumonia among patients with at least
      one of the established risk factors; the adjusted OR was 2.29 (95% confidence
      interval [CI]=2.20 to 2.39). In addition, patients with the following conditions
      had a higher risk of pneumonia despite adjustment for known risk factors and
      confounders: stroke or transient ischaemic attack, rheumatoid arthritis,
      Parkinson's disease, cancers, multiple sclerosis, dementia, and osteoporosis. The
      adjusted OR for pneumonia among patients without an established risk factor but
      with at least one of the new conditions was 2.44 (95% CI=2.24 to 2.65).
      CONCLUSION: As well as confirming some established risk factors, this study has
      determined seven new independent risk factors for community-acquired pneumonia.

PMID- 19843414
TI  - The commercialisation of GP services: a survey of APMS contracts and new GP
      ownership.
AB  - BACKGROUND: Alternative provider of medical services (APMS) legislation enables
      private commercial firms to provide NHS primary care. There is no central
      monitoring of APMS adoption by primary care trusts (PCTs), the new providers, or
      market competition. AIM: The aims were to: examine APMS contract data on bidders
      and providers, patient numbers, contract value, duration, and services; present a
      typology of primary care providers; establish the extent of competition; and
      identify which commercial providers have entered the English primary care market.
      DESIGN OF STUDY: Cross-sectional study. SETTING: All PCTs in England. METHOD: A
      survey was carried out in March 2008 gathering information on the number of APMS
      contracts, their value and duration, patient numbers, the successful tender, and
      other bidders. RESULTS: A total of 141 out of 152 PCTs provided information on 71
      APMS contracts that had been awarded and 66 contracts that were out to tender. Of
      those contracts awarded, 36 went to 14 different commercial companies, 28 to
      independent GP contractors, seven to social enterprises, and two to a PCT-managed
      service; one contract is shared by three different provider types. In more than
      half of the responses information on competition was not disclosed. In a fifth of
      those contracts awarded to the commercial sector, for which there is information
      on other bidders, there was no competition. Contracts varied widely, covering
      from one to several hundred thousand patients, with a value of pound6000-12
      million, and lasting from 1 year to being open-ended. Most contracts offered
      standard, essential, additional, and enhanced services; only a few were for
      specialist services. CONCLUSION: The lack of data on cost, patient services, and
      staff makes it impossible to evaluate value for money or quality, and the absence
      of competition is a further concern. There needs to be a proper evaluation of the
      APMS policy from the perspective of value for money and quality of care, as well
      as patient access and coverage.

PMID- 19843417
TI  - The antibiotic revolution should be more focused.

PMID- 19843415
TI  - Violations of medical confidentiality: opinions of primary care physicians.
AB  - BACKGROUND: Physicians should be able to distinguish situations where they need
      to protect confidentiality from those where they could be obligated to reveal
      information. Data are scarce concerning physician's attitudes in daily situations
      where violations of confidentiality are avoidable. Physicians should be aware of
      situations where patients are identifiable. AIM: To solicit participation of
      primary care physicians in a teaching intervention and to explore participants'
      opinions on violations of confidentiality. DESIGN OF STUDY: A questionnaire
      presented seven vignettes describing avoidable violations of confidentiality (for
      example, without patient consent a physician mentions a politician's illness
      their spouse). Participants answered on a scale of 0-3 (0=no violation and
      3=serious violation). All contacted physicians were invited to a teaching session
      during which the study results were discussed. METHOD: Three-hundred and seventy
      eight members of the Association of Physicians in Geneva (community physicians)
      working in primary care medicine, and 130 GPs and internists working at the
      University Hospital of Geneva (hospital physicians) took part. Physicians'
      answers were compared to responses from Swiss, UK, and other European law
      professors, and from 311 medical and law students in Geneva. RESULTS: Between 4%
      (case 6) and 57% (case 2), of physicians thought that no violation occurred. Law
      professors attributed the scores to each case as 3, 3, 2, 3, 2, 3, 3; the means
      of physicians were: 1.9, 1.4, 0.7, 1.4 (hospital physicians)/1.9 (community
      physicians), 0.4, 1.6, 2.6. In most cases, physicians' and students' answers were
      similar. A significantly higher percentage of community physicians than hospital
      physicians and students thought that a physician violates confidentiality if they
      provide the list of their patients to the police for the investigation of the
      theft of a purse in the waiting room. CONCLUSION: Physicians need to be fully
      aware of their obligations towards patient confidentiality. Avoidable breaches of
      confidentiality occur when colleagues and authorities (such as police and those
      in a judicial context) ask for information.

PMID- 19843418
TI  - Confidentiality: a contested value.

PMID- 19843419
TI  - Medical ethics and the healthcare rights of citizens and others.

PMID- 19843420
TI  - Health literacy: a necessity for increasing participation in health care.

PMID- 19843421
TI  - Effect of antibiotic prescribing strategies and an information leaflet on longer
      term reconsultation for acute lower respiratory tract infection.
AB  - BACKGROUND: Limited evidence suggests that delayed prescribing may influence
      future consultation behaviour. AIM: To assess the effects of antibiotic
      prescribing strategy on reconsultation in the year following presentation with
      acute lower respiratory tract infection (LRTI). DESIGN OF STUDY: Balanced
      factorial randomised trial. SETTING: Primary care. METHOD: Eight hundred and
      seven subjects, aged>or=3 years, had acute illness presenting with cough as the
      main symptom, plus at least one symptom or sign from sputum, chest pain, dyspnoea
      or wheeze. The subjects were randomised to one of three prescribing strategies
      (antibiotics, delayed antibiotic, no antibiotic) and a leaflet. Prior antibiotic
      use and reconsultation were assessed by medical record review. RESULTS: Patients
      who had been prescribed antibiotic for cough in the previous 2 years were much
      more likely to reconsult (incidence rate ratio [IRR]=2.55, 95% confidence
      interval [CI]=1.62 to 4.01) and use of a delayed prescription strategy is
      associated with reduced reconsultation in this group. In those with prior
      antibiotic exposure, there was a 34% reduction in consultation rate in the no
      antibiotic group (IRR=0.66, 0.30 to 1.44, P=0.295) and a 78% reduction for the
      delayed antibiotic group (IRR=0.22, 0.10 to 0.49, P<0.001) when compared with
      those given immediate antibiotics. This effect was not observed in patients who
      had not been prescribed antibiotics in the previous 2 years; there was no
      reduction in consultations in the no antibiotic group (IRR=1.23, 0.79 to 1.92,
      P=0.358) or the delayed antibiotic group (1.19, 0.78 to 1.80, P=0.426). There was
      an increase in consultation rate with an information leaflet (IRR=1.27, 0.86 to
      1.87, P=0.229). Past attendance with cough, or past attendance with other
      respiratory illness and smoking, also predicted reconsultation with cough.
      CONCLUSION: Delayed antibiotic prescribing for LRTI appears effective in
      modifying reconsultation behaviour, particularly in those with a prior history of
      antibiotic prescription for LRTI.

PMID- 19843422
TI  - Predictors of patient-initiated reconsultation for lower respiratory tract
      infections in general practice.
AB  - Reconsultation for lower respiratory tract infection (LRTI) is common in general
      practice, but those who reconsult rarely have more significant illness warranting
      antibiotics. Knowledge of factors that predict patient-initiated reconsultation
      may allow clinicians to address specific issues during the initial consultation
      that could reduce reconsultations. Thirty-three per cent of a cohort of 431 LRTI
      patients in a randomised controlled trial reconsulted. Excluding 35 patients with
      GP-requested reconsultation left 28% (112/396) with a patient-initiated
      reconsultation during 28-day follow-up. Patient-reported dyspnoea and concerns
      that persisted after the initial consultation independently predicted patient
      initiated reconsultation.

PMID- 19843423
TI  - Commentary: What's so special about familial hypercholesterolaemia?

PMID- 19843424
TI  - ENT 2-Week Wait audit.

PMID- 19843425
TI  - Early experience.

PMID- 19843426
TI  - Bell's palsy and Lyme disease.

PMID- 19843427
TI  - Mozart in my practice.

PMID- 19843429
TI  - Health inequalities in the UK: remedy requires action beyond redistribution of
      wealth.

PMID- 19843431
TI  - Simple advice to reduce salt intake.

PMID- 19843435
TI  - Achilles tendon rupture in athletes.
AB  - Achilles tendon ruptures commonly affect middle-aged athletes and can result in
      considerable functional impairment. While the cause is multifactorial, the
      greatest risk is present for athletes involved in sports that involve sudden
      acceleration and deceleration. A thorough history and physical examination can
      accurately yield a diagnosis, but when question remains, magnetic resonance
      imaging is superior to ultrasound-guided evaluation. The best evidence available
      suggests that operative treatment has a lower rate of rerupture, a higher rate of
      return to the same level of sport participation, and a higher complication rate,
      if an open technique is used. Percutaneous methods of fixation have lower
      complication rates without an increase in the rate of rerupture when compared
      with open methods. Augmentation of an Achilles tendon repair has demonstrated no
      clinical benefit. Rehabilitation with early mobilization leads to improved
      patient-reported outcomes.

PMID- 19843436
TI  - Scheuermann's Kyphosis: an update.
AB  - A review of the current literature demonstrates considerable debate regarding the
      pathogenesis, natural history and treatment of Scheuermann's kyphosis. Most of
      the views and recommendations provided in various reports are weakly supported by
      levels of evidence. In addition, prospective studies using validated
      questionnaire instruments and long-term follow-ups to assess clinical outcomes in
      patients treated conservatively or surgically versus those untreated that would
      document the natural history of the condition are still unavailable. This
      systematic review summarizes the current knowledge on Scheuermann's kyphosis and
      attempts to present a rational approach in the evaluation and management of this
      group of patients.

PMID- 19843437
TI  - Relationship between intraoperative femoral head bleeding and development of
      avascular necrosis after acetabular fracture surgery.
AB  - The purpose of this study was to determine whether the presence or absence of
      bleeding after drilling of the femoral head can be used to predict the
      development of avascular necrosis (AVN) after operative treatment of acetabular
      fractures. A computerized medical record search from 1996 to 2005 of all patients
      with an operatively treated acetabular fracture yielded 146 patients who had an
      intraoperative assessment of the vascularity of their femoral head and 72 of whom
      were available for a minimum of 12 months of follow-up. The average time to the
      development of AVN was 99.6 weeks with a range of 21-290 weeks. Eleven of the
      patients in the analysis eventually developed AVN. The p value is not significant
      at. 092. Although the difference between groups is not significant, it does
      appear that there is a relationship between femoral head bleeding and the
      development of avascular necrosis.

PMID- 19843438
TI  - Can patterns of segmental injuries of the foot and ankle predict amputation and
      disability?
AB  - The purpose of the study was to determine the risk of digital or distal segmental
      amputation and permanent unemployment in patients with these injury patterns. A
      retrospective chart review of 23 patients with multiple, ipsilateral injuries of
      the foot and ankle was performed. Amputations occurred in five patients (21.7%)
      and were most common in those with three-level injuries. Odds ratios showed that
      patients with an amputation were 9.75 times more likely to have a three-level
      injury than a two-level injury. At a mean follow-up of 12.9 months, 12 patients
      had not returned to work (60%), seven returned with restrictions, and only one
      patient returned to preinjury activities. It was concluded that patients with
      segmental foot and ankle injuries are at risk for amputation of the distal
      portion of the involved extremity and inability to return to their preinjury
      employment level (disability).

PMID- 19843439
TI  - AO types C3.1 and C3.2 distal radius fractures: functional outcomes.
AB  - The purpose of the current study was to examine the functional outcomes of C3.1
      and C3.2 distal radius fractures. A trauma registry was used to identify patients
      with C3.1 and C3.2 distal radius fractures (n = 33). Clinical follow-up consisted
      of completion of the Disabilities of the Arm, Shoulder, and Hand (DASH)
      questionnaire and assignment of a Gartland and Werley Demerit Point System score.
      Average follow-up duration was 62 months. Mean DASH score was 14 points; mean
      Gartland and Werley score was 6 points. Results were 14 excellent, 12 good, 10
      fair, and one poor. Patients regained an average of 78% of the flexion-extension
      arc, 94% of the pronation-supination arc, and 83% of grip strength compared with
      the uninjured side. Standardized and uniformly applied attempts at reconstruction
      of the distal radial articular surface led to successful outcomes in the majority
      of patients.

PMID- 19843440
TI  - Coccygectomy for the treatment of therapy-resistant coccygodynia.
AB  - Coccygodynia (pain in the region of the coccyx) has many causes, but it may be
      posttraumatic beginning after a fracture or contusion. Pain is typically
      triggered by or occurs while sitting. Nonsurgical management, including cushions,
      nonsteroidal anti-inflammatory drugs, and corticosteroid injections, can be
      successful in up to 85% of patients. The objective of the study was to show that
      coccygectomy can be a successful surgical treatment for patients who fail
      nonoperative treatment. This study is a retrospective analysis of all patients
      who underwent a coccygectomy performed by one surgeon between the years 2002 and
      2008. All patients were asked to complete an Oswestry low back pain disability
      questionnaire and a visual analog pain scale. The average Oswestry disability
      score was 25.75%. The average visual analog score was 3.4 cm. Four patients
      sustained a wound breakdown. The study concluded that for patients with
      conservative therapy-resistant coccygodynia, operative treatment with
      coccygectomy is a feasible management option.

PMID- 19843441
TI  - Cementless porous-coated anatomic total hip arthroplasty at Duke: 18- to 24-year
      follow-up.
AB  - The porous-coated anatomic (PCA) total hip was a first-generation cementless
      implant system introduced in 1983 for both primary and revision total hip
      arthroplasty. Between February 1983 and June 1989, 219 uncemented PCA total hips
      were implanted in 194 patients as part of a multisurgeon, single-institution,
      prospective study. Short-term follow-up data were available on 212 hips at an
      average of 21.7 months. At the time of final follow-up, data were available on
      121 hips at an average of 20.2 years (range, 18-24 years). Of the surviving
      patients, 55% had undergone revision. Of those patients with known failure
      mechanisms, 66% underwent revision for isolated acetabular osteolysis or
      loosening, 23% for femoral component failure, and 11% for failure of both
      components. As has been reported in other series, the acetabular component
      appeared to be the most common cause for revision, while the femoral component
      proved more durable.

PMID- 19843442
TI  - Concomitant correction of spinal deformity and spasticity management with
      posterior instrumentation and baclofen pump implantation.
AB  - Patients with spastic quadriplegia secondary to cerebral palsy manifest with
      severe spasticity and often with neuromuscular scoliosis. In order to optimize
      treatment and minimize morbidity in selected cases, the authors present a
      surgical option concurrently addressing these problems. This study reviews one
      case and describes the surgical technique in detail where intrathecal baclofen
      pump implantation and posterior spinal fusion are concomitantly performed to
      manage spasticity and scoliosis, respectively.

PMID- 19843443
TI  - On the utilization of energy minimization to the study of ion selectivity.
AB  - The major pitfalls in studying ion selectivity in binding site models using
      energy minimization based methods are examined and discussed. It is shown that
      the properties derived from energy minimization are strongly configuration
      dependent and that the results should be interpreted with caution. It is
      concluded that computational studies of ion selectivity must include thermal
      fluctuations and entropic effects.

PMID- 19843444
TI  - One-dimensional mathematical model of the atrioventricular node including atrio
      nodal, nodal, and nodal-his cells.
AB  - Mathematical models are a repository of knowledge as well as research and
      teaching tools. Although action potential models have been developed for most
      regions of the heart, there is no model for the atrioventricular node (AVN). We
      have developed action potential models for single atrio-nodal, nodal, and nodal
      His cells. The models have the same action potential shapes and refractoriness as
      observed in experiments. Using these models, together with models for the
      sinoatrial node (SAN) and atrial muscle, we have developed a one-dimensional (1D)
      multicellular model including the SAN and AVN. The multicellular model has slow
      and fast pathways into the AVN and using it we have analyzed the rich behavior of
      the AVN. Under normal conditions, action potentials were initiated in the SAN
      center and then propagated through the atrium and AVN. The relationship between
      the AVN conduction time and the timing of a premature stimulus (conduction curve)
      is consistent with experimental data. After premature stimulation,
      atrioventricular nodal reentry could occur. After slow pathway ablation or block
      of the L-type Ca(2+) current, atrioventricular nodal reentry was abolished.
      During atrial fibrillation, the AVN limited the number of action potentials
      transmitted to the ventricle. In the absence of SAN pacemaking, the inferior
      nodal extension acted as the pacemaker. In conclusion, we have developed what we
      believe is the first detailed mathematical model of the AVN and it shows the
      typical physiological and pathophysiological characteristics of the tissue. The
      model can be used as a tool to analyze the complex structure and behavior of the
      AVN.

PMID- 19843445
TI  - Characterization of photoactivated singlet oxygen damage in single-molecule
      optical trap experiments.
AB  - Optical traps or "tweezers" use high-power, near-infrared laser beams to
      manipulate and apply forces to biological systems, ranging from individual
      molecules to cells. Although previous studies have established that optical
      tweezers induce photodamage in live cells, the effects of trap irradiation have
      yet to be examined in vitro, at the single-molecule level. In this study, we
      investigate trap-induced damage in a simple system consisting of DNA molecules
      tethered between optically trapped polystyrene microspheres. We show that
      exposure to the trapping light affects the lifetime of the tethers, the
      efficiency with which they can be formed, and their structure. Moreover, we
      establish that these irreversible effects are caused by oxidative damage from
      singlet oxygen. This reactive state of molecular oxygen is generated locally by
      the optical traps in the presence of a sensitizer, which we identify as the
      trapped polystyrene microspheres. Trap-induced oxidative damage can be reduced
      greatly by working under anaerobic conditions, using additives that quench
      singlet oxygen, or trapping microspheres lacking the sensitizers necessary for
      singlet state photoexcitation. Our findings are relevant to a broad range of trap
      based single-molecule experiments-the most common biological application of
      optical tweezers-and may guide the development of more robust experimental
      protocols.

PMID- 19843446
TI  - Confinement regulates complex biochemical networks: initiation of blood clotting
      by "diffusion acting".
AB  - This study shows that environmental confinement strongly affects the activation
      of nonlinear reaction networks, such as blood coagulation (clotting), by small
      quantities of activators. Blood coagulation is sensitive to the local
      concentration of soluble activators, initiating only when the activators surpass
      a threshold concentration, and therefore is regulated by mass transport phenomena
      such as flow and diffusion. Here, diffusion was limited by decreasing the size of
      microfluidic chambers, and it was found that microparticles carrying either the
      classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus,
      initiated coagulation of human platelet-poor plasma only when confined. A simple
      analytical argument and numerical model were used to describe the mechanism for
      this phenomenon: confinement causes diffusible activators to accumulate locally
      and surpass the threshold concentration. To interpret the results, a
      dimensionless confinement number, Cn, was used to describe whether a stimulus was
      confined, and a Damkohler number, Da(2), was used to describe whether a
      subthreshold stimulus could initiate coagulation. In the context of initiation of
      coagulation by bacteria, this mechanism can be thought of as "diffusion acting",
      which is distinct from "diffusion sensing". The ability of confinement and
      diffusion acting to change the outcome of coagulation suggests that confinement
      should also regulate other biological "on" and "off" processes that are
      controlled by thresholds.

PMID- 19843447
TI  - Depletion effects massively change chromatin properties and influence genome
      folding.
AB  - We present a Monte Carlo model for genome folding at the 30-nm scale with focus
      on linker-histone and nucleosome depletion effects. We find that parameter
      distributions from experimental data do not lead to one specific chromatin fiber
      structure, but instead to a distribution of structures in the chromatin phase
      diagram. Depletion of linker histones and nucleosomes affects, massively, the
      flexibility and the extension of chromatin fibers. Increasing the amount of
      nucleosome skips (i.e., nucleosome depletion) can lead either to a collapse or to
      a swelling of chromatin fibers. These opposing effects are discussed and we show
      that depletion effects may even contribute to chromatin compaction. Furthermore,
      we find that predictions from experimental data for the average nucleosome skip
      rate lie exactly in the regime of maximum chromatin compaction. Finally, we
      determine the pair distribution function of chromatin. This function reflects the
      structure of the fiber, and its Fourier-transform can be measured experimentally.
      Our calculations show that even in the case of fibers with depletion effects, the
      main dominant peaks (characterizing the structure and the length scales) can
      still be identified.

PMID- 19843448
TI  - Dissecting the impact of matrix anchorage and elasticity in cell adhesion.
AB  - Extracellular matrices determine cellular fate decisions through the regulation
      of intracellular force and stress. Previous studies suggest that matrix stiffness
      and ligand anchorage cause distinct signaling effects. We show herein how defined
      noncovalent anchorage of adhesion ligands to elastic substrates allows for
      dissection of intracellular adhesion signaling pathways related to matrix
      stiffness and receptor forces. Quantitative analysis of the mechanical balance in
      cell adhesion using traction force microscopy revealed distinct scalings of the
      strain energy imparted by the cells on the substrates dependent either on matrix
      stiffness or on receptor force. Those scalings suggested the applicability of a
      linear elastic theoretical framework for the description of cell adhesion in a
      certain parameter range, which is cell-type-dependent. Besides the deconvolution
      of biophysical adhesion signaling, site-specific phosphorylation of focal
      adhesion kinase, dependent either on matrix stiffness or on receptor force, also
      demonstrated the dissection of biochemical signaling events in our approach.
      Moreover, the net contractile moment of the adherent cells and their strain
      energy exerted on the elastic substrate was found to be a robust measure of cell
      adhesion with a unifying power-law scaling exponent of 1.5 independent of matrix
      stiffness.

PMID- 19843449
TI  - Spatial distribution and mobility of the Ran GTPase in live interphase cells.
AB  - The GTPase Ran is a key regulator of molecular transport through nuclear pore
      complex (NPC) channels. To analyze the role of Ran in its nuclear transport
      function, we used several quantitative fluorescence techniques to follow the
      distribution and dynamics of an enhanced yellow fluorescent protein (EYFP)-Ran in
      HeLa cells. The diffusion coefficient of the majority of EYFP-Ran molecules
      throughout the cells corresponded to an unbound state, revealing the remarkably
      dynamic Ran regulation. Although we observed no significant immobile Ran
      populations in cells, approximately 10% of the cytoplasmic EYFP-Ran and 30% of
      the nuclear EYFP-Ran exhibited low mobility indicative of molecular interactions.
      The high fraction of slow nuclear EYFP-Ran reflects the expected numerous
      interactions of nuclear RanGTP with nuclear transport receptors. However, it is
      not high enough to support retention mechanisms as the main cause for the
      observed nuclear accumulation of Ran. The highest cellular concentration of EYFP
      Ran was detected at the nuclear envelope, corresponding to approximately 200
      endogenous Ran molecules for each NPC, and exceeding the currently estimated NPC
      channel transport capacity. Together with the relatively long residence time of
      EYFP-Ran at the nuclear envelope (33 +/- 14 ms), these observations suggest that
      only a fraction of the Ran concentrated at NPCs transits through NPC channels.

PMID- 19843450
TI  - Electrotonic coupling between human atrial myocytes and fibroblasts alters
      myocyte excitability and repolarization.
AB  - Atrial fibrosis has been implicated in the development and maintenance of atrial
      arrhythmias, and is characterized by expansion of the extracellular matrix and an
      increased number of fibroblasts (Fbs). Electrotonic coupling between atrial
      myocytes and Fbs may contribute to the formation of an arrhythmogenic substrate.
      However, the role of these cell-cell interactions in the function of both normal
      and diseased atria remains poorly understood. The goal of this study was to gain
      mechanistic insight into the role of electrotonic Fb-myocyte coupling on myocyte
      excitability and repolarization. To represent the system, a human atrial myocyte
      (hAM) coupled to a variable number of Fbs, we employed a new ionic model of the
      hAM, and a variety of membrane representations for atrial Fbs. Simulations
      elucidated the effects of altering the intercellular coupling conductance,
      electrophysiological Fb properties, and stimulation rate on the myocyte action
      potential. The results demonstrate that the myocyte resting potential and action
      potential waveform are modulated strongly by the properties and number of coupled
      Fbs, the degree of coupling, and the pacing frequency. Our model provides
      mechanistic insight into the consequences of heterologous cell coupling on hAM
      electrophysiology, and can be extended to evaluate these implications at both
      tissue and organ levels.

PMID- 19843451
TI  - Anastral spindle assembly: a mathematical model.
AB  - Assembly of an anastral spindle was modeled as a two-stage process: first, the
      aggregation of microtubule foci or asters around the chromosomes, and second, the
      elongation of cross-linked microtubules and onset of bipolarity. Several
      possibilities involving diffusion and transport were investigated for the first
      stage, and the most feasible was found to be binding of the asters to
      cytoskeletal filaments and directed transport toward the chromosomes. For the
      second stage, a differential-equation model was formulated and solved
      numerically; it involves cross-linking of microtubules with those aligned with
      the spindle axis and between microtubules bound to different chromosomes, and
      sliding of microtubules along the spindle axis to elongate the spindle. Ncd was
      postulated to perform both functions. The model shows that spindle formation
      begins with rapid cross-linking of microtubules, followed by elongation, which
      continues until the population of microtubules aligned with the spindle axis is
      depleted and microtubules cross-linking different chromosomes dominate. It also
      shows that when sliding is inhibited, short bipolar spindles still form, and if
      clustering is enhanced, normal-length spindles can form, although requiring
      longer assembly time. These findings are consistent with spindle assembly in live
      wild-type and ncd mutant Drosophila oocytes.

PMID- 19843452
TI  - Two-path impedance spectroscopy for measuring paracellular and transcellular
      epithelial resistance.
AB  - Solutes are transported across epithelial cell layers via transcellular and
      paracellular pathways. The transcellular pathway leads across the apical and
      basolateral cell membrane, whereas the paracellular pathway is directed through
      the tight junction. Tight junction proteins (claudins, occludin, tricellulin) can
      not only form barriers but also paracellular channels that are--in concert with
      membrane channels and transporters--regulated in a wide range in health and
      disease states. Thus, it is desirable to determine para- and transcellular
      resistance (R(para), R(trans)) separately. This cannot be achieved by
      conventional transepithelial resistance (TER) measurements. We present an
      impedance spectroscopic approach that is optimized for differentiation between
      these two pathways. The method is based on a transepithelial impedance
      measurement in specialized Ussing chambers, combined with a Ca(2+)-dependent
      modulation of R(para) through EGTA and flux measurements of a nonradioactive
      paracellular marker, fluorescein. The prerequisites are a paracellular marker
      that varies in parallel to 1/R(para), an experimental regime that alters R(para)
      without affecting R(trans), and exact knowledge of the resistance of
      subepithelial components. The underlying prerequisites and the applicability as a
      routine method were verified on cell lines of different tightness including HT
      29/B6 colon cells and Madin-Darby canine kidney tubule cells C7 and C11.

PMID- 19843453
TI  - Reinterpreting the anomalous mole fraction effect: the ryanodine receptor case
      study.
AB  - The origin of the anomalous mole fraction effect (AMFE) in calcium channels is
      explored with a model of the ryanodine receptor. This model predicted and
      experiments verified new AMFEs in the cardiac isoform. In mole fraction
      experiments, conductance is measured in mixtures of ion species X and Y as their
      relative amounts (mole fractions) vary. This curve can have a minimum (an AMFE).
      The traditional interpretation of the AMFE is that multiple interacting ions move
      through the pore in a single file. Mole fraction curves without minima (no AMFEs)
      are generally interpreted as X displacing Y from the pore in a proportion larger
      than its bath mole fraction (preferential selectivity). We find that the AMFE is
      also caused by preferential selectivity of X over Y, if X and Y have similar
      conductances. This is a prediction applicable to any channel and provides a
      fundamentally different explanation of the AMFE that does not require single
      filing or multiple occupancy: preferential selectivity causes the resistances to
      current flow in the baths, channel vestibules, and selectivity filter to change
      differently with mole fraction, and produce the AMFE.

PMID- 19843454
TI  - Spatial and temporal dynamics of mitochondrial membrane permeability waves during
      apoptosis.
AB  - Change in the permeability of the mitochondrial membrane to proteins (cytochrome
      c and Smac) and protons is a critical step in apoptosis. Although the time from
      the induction of apoptosis to the change of mitochondrial permeability is
      variable over a period of hours, the release of proteins is an "all or none"
      phenomenon that is completed in an individual cell within minutes. Here, using
      single-cell fluorescence microscopy, we show that the release of cytochrome c
      from a single mitochondrion occurs in a single step. However, this increased
      permeability of the outer membrane to cytochrome c propagates throughout the cell
      as a slower, spatially coordinated wave. The permeability of the outer membrane
      to Smac propagates with the same spatial pattern but lagging in time. This is
      followed by a wave of increased permeability of the inner membrane to protons.
      Only afterward do the mitochondria fission. The spatial dependence of the
      permeability wave was inhibited by thapsigargin, an inhibitor of the endoplasmic
      reticulum calcium pumps, but buffering cytosolic calcium had no effect. These
      results show that the trigger for apoptosis is spatially localized, initiating at
      one or only a few mitochondria preceding the loss of mitochondrial energetics,
      and the subsequent temporal propagation of mitochondrial membrane permeability is
      calcium-dependent.

PMID- 19843455
TI  - Factor XA binding to phosphatidylserine-containing membranes produces an inactive
      membrane-bound dimer.
AB  - Factor Xa (FXa) has a prominent role in amplifying both inflammation and the
      coagulation cascade. In the coagulation cascade, its main role is catalyzing the
      proteolytic activation of prothrombin to thrombin. Efficient proteolysis is well
      known to require phosphatidylserine (PS)-containing membranes that are provided
      by platelets in vivo. However, soluble, short-chain PS also triggers efficient
      proteolytic activity and formation of an inactive FXa dimer in solution. In this
      work, we ask whether PS-containing membranes also trigger formation of an
      inactive FXa dimer. We determined the proteolytic activity of human FXa toward
      human Pre2 as a substrate both at fixed membrane concentration (increasing FXa
      concentration) and at fixed FXa concentration (increasing membrane
      concentration). Neither of these experiments showed the expected behavior of an
      increase in activity as FXa bound to membranes, but instead suggested the
      existence of a membrane-bound inactive form of FXa. We found also that the
      fluorescence of fluorescein attached to FXa's active site serine was depolarized
      in a FXa concentration-dependent fashion in the presence of membranes. The
      fluorescence lifetime of FXa labeled in its active sites with a dansyl
      fluorophore showed a similar concentration dependence. We explained all these
      observations in terms of a quantitative model that takes into account
      dimerization of FXa after binding to a membrane, which yielded estimates of the
      FXa dimerization constant on a membrane as well as the kinetic constants of the
      dimer, showing that the dimer is effectively inactive.

PMID- 19843456
TI  - New insights into the stratum corneum lipid organization by X-ray diffraction
      analysis.
AB  - The characteristic 13-nm lamellar phase that is formed by lipids in the outermost
      layer of the skin, the stratum corneum (SC), is very important for the barrier
      function of the skin. To gain more insight into the molecular organization of
      this lamellar phase, we performed small-angle x-ray diffraction (SAXD) using
      various lipid mixtures mimicking the lipid composition in SC. In the SAXD pattern
      of each mixture, at least seven diffraction orders were observed, attributed to
      the lamellar phase with a repeat distance ranging from 12.1 to 13.8 nm. Using the
      sampling method based on the variation in repeat distance, we selected phase
      angles for the first six diffraction orders. Using these phase angles for the
      lamellar phase, a high-resolution electron density distribution could be
      calculated. Subsequently, from SAXD patterns of isolated SC, the electron density
      distribution of the lamellar phase was also calculated and appeared to be very
      similar to that in the lipid mixtures. This demonstrates that the lipid mixtures
      serve as an excellent model for the lipid organization in SC, not only with
      respect to the repeat distance, but also in terms of the electron density
      distribution within the unit cell.

PMID- 19843457
TI  - Cell-wall interactions and the selective bacteriostatic activity of a miniature
      oligo-acyl-lysyl.
AB  - The oligo-acyl-lysyl, C(12(omega 7))K-beta(12), is comprised of only three Lys
      residues. Despite its small size, it exhibits potent bacteriostatic activity
      against Gram-positive bacteria, but it is approximately 10-fold less potent
      against Gram-negative bacteria. We followed the interactions of C(12(omega 7))K
      beta(12) from its initial contact with the bacterial surface across the cell wall
      down to the cytoplasmic membrane. Binding to anionic lipids, as well as to
      negatively charged LPS and LTA, occurs with very high affinity. The C(12(omega
      7))K-beta(12) does not cross the outer membrane of Gram-negative bacteria;
      rather, it achieves its action by depositing on the LPS layer, promoting surface
      adhesion and blocking passage of solutes. In Gram-positive bacteria, the thick
      peptidoglycan layer containing LTA allows passage of C(12(omega 7))K-beta(12) and
      promotes its accumulation in the small periplasm. From that location it is then
      driven to the membrane by strong electrostatic interactions. Despite its high
      potency against Gram-positive bacteria, this agent is not capable of efficiently
      breaking down the permeability barrier of the cytoplasmic membrane or of reaching
      an intracellular target, as suggested by the fact that it does not interact with
      DNA.

PMID- 19843458
TI  - Tilt and rotation angles of a transmembrane model peptide as studied by
      fluorescence spectroscopy.
AB  - In this study the membrane orientation of a tryptophan-flanked model peptide,
      WALP23, was determined by using peptides that were labeled at different positions
      along the sequence with the environmentally sensitive fluorescent label BADAN.
      The fluorescence properties, reflecting the local polarity, were used to
      determine the tilt and rotation angles of the peptide based on an ideal alpha
      helix model. For WALP23 inserted in dioleoylphosphatidylcholine (DOPC), an
      estimated tilt angle of the helix with respect to the bilayer normal of 24
      degrees +/- 5 degrees was obtained. When the peptides were inserted into bilayers
      with different acyl chain lengths or containing different concentrations of
      cholesterol, small changes in tilt angle were observed as response to hydrophobic
      mismatch, whereas the rotation angle appeared to be independent of lipid
      composition. In all cases, the tilt angles were significantly larger than those
      previously determined from (2)H NMR experiments, supporting recent suggestions
      that the relatively long timescale of (2)H NMR measurements may result in an
      underestimation of tilt angles due to partial motional averaging. It is concluded
      that although the fluorescence technique has a rather low resolution and limited
      accuracy, it can be used to resolve the discrepancies observed between previous
      (2)H NMR experiments and molecular-dynamics simulations.

PMID- 19843459
TI  - Curvature generation and pressure profile modulation in membrane by lysolipids:
      insights from coarse-grained simulations.
AB  - Although many membrane additives are known to modulate the activities of membrane
      proteins via perturbing the properties of lipid membrane, the underlying
      mechanism is often not precisely understood. In this study, we investigate the
      impact of asymmetrically incorporating single-tailed lysophosphatidylcholine
      (LPC) into a membrane bilayer using coarse-grained molecular dynamics
      simulations. Using a simple computational protocol designed to approximately
      mimic a micropipette setting, we show that asymmetric incorporation of LPC can
      lead to significant curvature in a bilayer. Detailed analysis of geometrical and
      mechanical properties (pressure profile) of the resulting mound structure
      indicates that the degree of pressure profile perturbation is determined not by
      the local curvature per se but by the packing of lipid headgroups (i.e., area-per
      lipid). The findings help provide a concrete basis for understanding the
      activation mechanism of mechanosensitive channels by asymmetric incorporation of
      LPC into membrane patches in patch-clamp experiments. The calculated local
      pressure profiles are valuable to the construction of realistic membrane models
      for the analysis of mechanosensation in a continuum mechanics framework.

PMID- 19843461
TI  - Novel ways to determine kinesin-1's run length and randomness using fluorescence
      microscopy.
AB  - The molecular motor protein Kinesin-1 drives intracellular transport of vesicles,
      by binding to microtubules and making hundreds of consecutive 8-nm steps along
      them. Three important parameters define the motility of such a linear motor:
      velocity, run length (the average distance traveled), and the randomness (a
      measure of the stochasticity of stepping). We used total internal reflection
      fluorescence microscopy to measure these parameters under conditions without
      external load acting on the motor. First, we tracked the motility of single motor
      proteins at different adenosine triphosphate (ATP) concentrations and determined
      both velocity and (for the first time, to our knowledge, by using single-molecule
      fluorescence assays) randomness. We show that the rate of Kinesin-1 at zero load
      is limited by two or more exponentially distributed processes at high ATP
      concentrations, but that an additional, ATP-dependent process becomes the sole
      rate-limiting process at low ATP concentrations. Next, we measured the density
      profile of moving Kinesin-1 along a microtubule. This allowed us to determine the
      average run length in a new way, without the need to resolve single-molecules and
      to correct for photobleaching. At saturating ATP concentration, we measured a run
      length of 1070 +/- 30 nm. This value did not significantly change for different
      ATP concentrations.

PMID- 19843460
TI  - Tuning passive mechanics through differential splicing of titin during skeletal
      muscle development.
AB  - During postnatal development, major changes in mechanical properties of skeletal
      muscle occur. We investigated passive properties of skeletal muscle in mice and
      rabbits that varied in age from 1 day to approximately 1 year. Neonatal skeletal
      muscle expressed large titin isoforms directly after birth, followed by a gradual
      switch toward progressively smaller isoforms that required weeks-to-months to be
      completed. This suggests an extremely high plasticity of titin splicing during
      skeletal muscle development. Titin exon microarray analysis showed increased
      expression of a large group of exons in neonatal muscle, when compared to adult
      muscle transcripts, with the majority of upregulated exons coding for the elastic
      proline-glutamate-valine-lysine (PEVK) region of titin. Protein analysis
      supported expression of a significantly larger PEVK segment in neonatal muscle.
      In line with these findings, we found >50% lower titin-based passive stiffness of
      neonatal muscle when compared to adult muscle. Inhibiting 3,5,3'-tri-iodo-L
      thyronine and 3,5,3',5'-tetra-iodo-L-thyronine secretion did not alter isoform
      switching, suggesting no major role for thyroid hormones in regulating
      differential titin splicing during postnatal development. In summary, our work
      shows that stiffening of skeletal muscle during postnatal development occurs
      through a decrease in titin isoform size, due mainly to a marked restructuring of
      the PEVK region of titin.

PMID- 19843462
TI  - Mechanism of cis-inhibition of polyQ fibrillation by polyP: PPII oligomers and
      the hydrophobic effect.
AB  - PolyQ peptides teeter between polyproline II (PPII) and beta-sheet conformations.
      In tandem polyQ-polyP peptides, the polyP segment tips the balance toward PPII,
      increasing the threshold number of Gln residues needed for fibrillation. To
      investigate the mechanism of cis-inhibition by flanking polyP segments on polyQ
      fibrillation, we examined short polyQ, polyP, and tandem polyQ-polyP peptides.
      These polyQ peptides have only three glutamines and cannot form beta-sheet
      fibrils. We demonstrate that polyQ-polyP peptides form small, soluble oligomers
      at high concentrations (as shown by size exclusion chromatography and diffusion
      coefficient measurements) with PPII structure (as shown by circular dichroism
      spectroscopy and (3)J(HN-C alpha) constants of Gln residues from constant time
      correlation spectroscopy NMR). Nuclear Overhauser effect spectroscopy and
      molecular modeling suggest that self-association of these peptides occurs as a
      result of both hydrophobic and steric effects. Pro side chains present three
      methylenes to solvent, favoring self-association of polyP through the hydrophobic
      effect. Gln side chains, with two methylene groups, can adopt a conformation
      similar to that of Pro side chains, also permitting self-association through the
      hydrophobic effect. Furthermore, steric clashes between Gln and Pro side chains
      to the C-terminal side of the polyQ segment favor adoption of the PPII-like
      structure in the polyQ segment. The conformational adaptability of the polyQ
      segment permits the cis-inhibitory effect of polyP segments on fibrillation by
      the polyQ segments in proteins such as huntingtin.

PMID- 19843463
TI  - Probing neuroserpin polymerization and interaction with amyloid-beta peptides
      using single molecule fluorescence.
AB  - Neuroserpin is a member of the serine proteinase inhibitor superfamily. It can
      undergo a conformational transition to form polymers that are associated with the
      dementia familial encephalopathy with neuroserpin inclusion bodies and the wild
      type protein can inhibit the toxicity of amyloid-beta peptides in Alzheimer's
      disease. We have used a single molecule fluorescence method, two color
      coincidence detection, to determine the rate-limiting steps of the early stages
      of the polymerization of fluorophore-labeled neuroserpin and have assessed how
      this process is altered in the presence of A beta(1-40.) Our data show that
      neuroserpin polymerization proceeds first by the unimolecular formation of an
      active monomer, followed by competing processes of both polymerization and
      formation of a latent monomer from the activated species. These data are not in
      keeping with the recently proposed domain swap model of polymer formation in
      which the latent species and activated monomer are likely to be formed by
      competing pathways directly from the unactivated monomeric serpin. Moreover, the
      A beta(1-40) peptide forms a weak complex with neuroserpin (dissociation constant
      of 10 +/- 5 nM) that increases the amount of active monomer thereby increasing
      the rate of polymerization. The A beta(1-40) is displaced from the complex so
      that it acts as a catalyst and is not incorporated into neuroserpin polymers.

PMID- 19843464
TI  - The quaternary structure of amalgam, a Drosophila neuronal adhesion protein,
      explains its dual adhesion properties.
AB  - Amalgam (Ama) is a secreted neuronal adhesion protein that contains three tandem
      immunoglobulin domains. It has both homophilic and heterophilic cell adhesion
      properties, and is required for axon guidance and fasciculation during early
      stages of Drosophila development. Here, we report its biophysical
      characterization and use small-angle x-ray scattering to determine its low
      resolution structure in solution. The biophysical studies revealed that Ama forms
      dimers in solution, and that its secondary and tertiary structures are typical
      for the immunoglobulin superfamily. Ab initio and rigid-body modeling by small
      angle x-ray scattering revealed a distinct V-shaped dimer in which the two
      monomer chains are aligned parallel to each other, with the dimerization
      interface being formed by domain 1. These data provide a structural basis for the
      dual adhesion characteristics of Ama. Thus, the dimeric structure explains its
      homophilic adhesion properties. Its V shape suggests a mechanism for its
      interaction with its receptor, the single-pass transmembrane adhesion protein
      neurotactin, in which each "arm" of Ama binds to the extracellular domain of
      neurotactin, thus promoting its clustering on the outer face of the plasma
      membrane.

PMID- 19843465
TI  - Defining coarse-grained representations of large biomolecules and biomolecular
      complexes from elastic network models.
AB  - Coarse-grained (CG) models of large biomolecular complexes enable simulations of
      these systems over long timescales that are not accessible for atomistic
      molecular dynamics (MD) simulations. A systematic methodology, called essential
      dynamics coarse-graining (ED-CG), has been developed for defining coarse-grained
      sites in a large biomolecule. The method variationally determines the CG sites so
      that key dynamic domains in the protein are preserved in the CG representation.
      The original ED-CG method relies on a principal component analysis (PCA) of a MD
      trajectory. However, for many large proteins and multi-protein complexes such an
      analysis may not converge or even be possible. This work develops a new ED-CG
      scheme using an elastic network model (ENM) of the protein structure. In this
      procedure, the low-frequency normal modes obtained by ENM are used to define
      dynamic domains and to define the CG representation accordingly. The method is
      then applied to several proteins, such as the HIV-1 CA protein dimer, ATP-bound G
      actin, and the Arp2/3 complex. Numerical results show that ED-CG with ENM (ENM-ED
      CG) is much faster than ED-CG with PCA because no MD is necessary. The ENM-ED-CG
      models also capture functional essential dynamics of the proteins almost as well
      as those using full MD with PCA. Therefore, the ENM-ED-CG method may be better
      suited to coarse-grain a very large biomolecule or biomolecular complex that is
      too computationally expensive to be simulated by conventional MD, or when a high
      resolution atomic structure is not even available.

PMID- 19843466
TI  - Common structural transitions in explicit-solvent simulations of villin headpiece
      folding.
AB  - Molecular dynamics simulations of protein folding can provide very high
      resolution data on the folding process; however, due to computational challenges
      most studies of protein folding have been limited to small peptides, or made use
      of approximations such as Go potentials or implicit solvent models. We have
      performed a set of molecular dynamics simulations totaling >50 micros on the
      villin headpiece subdomain, one of the most stable and fastest-folding naturally
      occurring proteins, in explicit solvent. We find that the wild-type villin
      headpiece reliably folds to a native conformation on timescales similar to
      experimentally observed folding, but that a fast folding double-norleucine mutant
      shows significantly more heterogeneous behavior. Along with other recent
      simulation studies, we note the occurrence of nonnative structures intermediates,
      which may yield a nativelike signal in the fluorescence measurements typically
      used to study villin folding. Based on the wild-type simulations, we propose
      alternative approaches to measure the formation of the native state.

PMID- 19843467
TI  - Polarization-sensitive two-photon microscopy study of the organization of liquid
      crystalline DNA.
AB  - Highly concentrated DNA solutions exhibit self-ordering properties such as the
      generation of liquid-crystalline phases. Such organized domains may play an
      important role in the global chromatin topology but can also be used as a simple
      model for the study of more complex 3D DNA structures. In this work, using
      polarized two-photon fluorescence microscopy, we report on the orientation of DNA
      molecules in liquid-crystalline phases. For this purpose, we analyze the signal
      emitted by fluorophores that are noncovalently bound to DNA strands. In nonlinear
      processes, excitation occurs exclusively in the focal volume, which offers
      advantages such as the reduction of photobleaching of out-of-focus molecules and
      intrinsic 3D sectioning capability. Propidium iodide and Hoechst, two
      fluorophores with different DNA binding modes, have been considered. Polarimetric
      measurements show that the dyes follow the alignment with respect to the DNA
      strands and allow the determination of the angles between the emission dipoles
      and the longitudinal axis of the DNA double strand. These results provide a
      useful starting point toward the application of two-photon polarimetry techniques
      to determine the local orientation of condensed DNA in physiological conditions.

PMID- 19843468
TI  - Streptavidin 2D crystal substrates for visualizing biomolecular processes by
      atomic force microscopy.
AB  - Flat substrate surfaces are a key to successful imaging of biological
      macromolecules by atomic force microscopy (AFM). Although usable substrate
      surfaces have been prepared for still imaging of immobilized molecules, surfaces
      that are more suitable have recently been required for dynamic imaging to
      accompany the progress of the scan speed of AFM. In fact, the state-of-the-art
      high-speed AFM has achieved temporal resolution of 30 ms, a capacity allowing us
      to trace molecular processes played by biological macromolecules. Here, we
      characterize three types of streptavidin two-dimensional crystals as substrates,
      concerning their qualities of surface roughness, uniformity, stability, and
      resistance to nonspecific protein adsorption. These crystal surfaces are commonly
      resistant to nonspecific protein adsorption, but exhibit differences in other
      properties to some extent. These differences must be taken into consideration,
      but these crystal surfaces are still useful for dynamic AFM imaging, as
      demonstrated by observation of calcium-induced changes in calmodulin, GroES
      binding to GroEL, and actin polymerization on the surfaces.

PMID- 19843469
TI  - Quantitative comparison of different fluorescent protein couples for fast FRET
      FLIM acquisition.
AB  - The fluorescent-protein based fluorescence resonance energy transfer (FRET)
      approach is a powerful method for quantifying protein-protein interactions in
      living cells, especially when combined with fluorescence lifetime imaging
      microscopy (FLIM). To compare the performance of different FRET couples for FRET
      FLIM experiments, we first tested enhanced green fluorescent protein (EGFP)
      linked to different red acceptors (mRFP1-EGFP, mStrawberry-EGFP, HaloTag (TMR)
      EGFP, and mCherry-EGFP). We obtained a fraction of donor engaged in FRET (f(D))
      that was far from the ideal case of one, using different mathematical models
      assuming a double species model (i.e., discrete double exponential fixing the
      donor lifetime and double exponential stretched for the FRET lifetime). We show
      that the relatively low f(D) percentages obtained with these models may be due to
      spectroscopic heterogeneity of the acceptor population, which is partially caused
      by different maturation rates for the donor and the acceptor. In an attempt to
      improve the amount of donor protein engaged in FRET, we tested mTFP1 as a donor
      coupled to mOrange and EYFP, respectively. mTFP1 turned out to be at least as
      good as EGFP for donor FRET-FLIM experiments because 1), its lifetime remained
      constant during light-induced fluorescent changes; 2), its fluorescence decay
      profile was best fitted with a single exponential model; and 3), no
      photoconversion was detected. The f(D) value when combined with EYFP as an
      acceptor was the highest of all tandems tested (0.7). Moreover, in the context of
      fast acquisitions, we obtained a minimal f(D) (mf(D)) for mTFP1-EYFP that was
      almost two times greater than that for mCherry-EGFP (0.65 vs. 0.35). Finally, we
      compared EGFP and mTFP1 in a biological situation in which the fusion proteins
      were highly immobile, and EGFP and mTFP1 were linked to the histone H4 (EGFP-H4
      and mTFP1-H4) in fast FLIM acquisitions. In this particular case, the
      fluorescence intensity was more stable for EGFP-H4 than for mTFP1-H4.
      Nevertheless, we show that mTFP1/EYFP stands alone as the best FRET-FLIM couple
      in terms of f(D) analysis.

PMID- 19843470
TI  - The analytical specificity of human chorionic gonadotropin assays determined
      using WHO International Reference Reagents.
AB  - BACKGROUND: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein
      hormone with considerable molecular heterogeneity. There is uncertainty regarding
      which hCG variants are detected by different hCG assays. The analytical
      specificity of 8 hCG assays was investigated. METHODS: WHO International
      Reference Reagents for hCG, nicked hCG (hCGn), beta subunit (hCGbeta), nicked
      beta subunit (hCGbetan), and beta core fragment (hCGbetacf) were individually
      added to hCG-free human serum. Specimens were analyzed with 8 commercially
      available hCG assays. Equimolar detection of hCG variants was defined as a
      recovery of 90-110%. RESULTS: All assays detected hCG and hCGn with mean
      recoveries of 98.3 and 94.6%, respectively. Seven assays detected hCGbeta (mean
      recovery 103.8%) but with high variation, and equimolar detection was observed
      only in four. The mean recovery of hCGbetan was 85.5% but was highly variable
      with only two assays showing equimolar detection. With a mean recovery of 53.4%,
      two assays detected hCGbetacf and both underestimated it considerably.
      Information provided by the assay manufacturer regarding hCG variant analytical
      specificity was inadequate or unclear in 75% of the assays. CONCLUSIONS: hCG
      assays vary considerably in their ability to detect different hCG variants.
      Manufacturers of hCG assays should clearly indicate the hCG variant specificity
      of their reagent systems.

PMID- 19843471
TI  - Ten years of infliximab: insights from clinical trials in rheumatoid arthritis.
AB  - Early animal and open label human studies suggested a pivotal role for tumor
      necrosis factor (TNF) inhibition in the treatment of rheumatoid arthritis (RA).
      Subsequent randomized controlled trials with infliximab showed a rapid reduction
      of signs and symptoms as well as fast normalization of C reactive protein (CRP)
      in patients responding to treatment. In addition, a synergistic effect of
      methotrexate (MTX) in combination with infliximab was evident. Infliximab
      treatment can inhibit progression of structural joint damage, a newly reported
      outcome of TNF inhibition in rheumatoid arthritis shown to be largely independent
      of clinical response to infliximab treatment. Early treatment with infliximab in
      combination with methotrexate in methotrexate-naive patients showed similar
      inhibition of x-ray progression, and change of the natural course of disease thus
      became an achievable treatment goal in rheumatoid arthritis. Current clinical
      practice in rheumatology aims at obtaining low disease activity and remission
      state. Application of new treatment strategies with tight control of disease
      activity allows to reach these new treatment goals in many patients. The extended
      research programs of infliximab have added significant knowledge to our current
      clinical management of rheumatoid arthritis patients. We also learned, however,
      that anti-TNF treatment is not without risk, and that careful patient selection,
      screening, and monitoring are vital to achieve these outcomes in every day
      clinical practice.

PMID- 19843472
TI  - Nonvariceal upper gastrointestinal hemorrhage: probing beneath the surface.

PMID- 19843473
TI  - How will we address the crucial questions facing our field?
AB  - The following is an edited reprint of the presidential address delivered by
      Robert S. Sandler, MD, MPH, AGAF, during the American Gastroenterological
      Association Plenary Session at Digestive Disease Week 2009.

PMID- 19843474
TI  - MeCP2 controls an epigenetic pathway that promotes myofibroblast
      transdifferentiation and fibrosis.
AB  - BACKGROUND & AIMS: Myofibroblast transdifferentiation generates hepatic
      myofibroblasts, which promote liver fibrogenesis. The peroxisome proliferator
      activated receptor gamma (PPARgamma) is a negative regulator of this process. We
      investigated epigenetic regulation of PPARgamma and myofibroblast
      transdifferentiation. METHODS: Chromatin immunoprecipitation (ChIP) assays
      assessed the binding of methyl-CpG binding protein 2 (MeCP2) to PPARgamma and
      chromatin modifications that silence this gene. MeCP2(-/y) mice and an inhibitor
      (DZNep) of the epigenetic regulatory protein EZH2 were used in the carbon
      tetrachloride model of liver fibrosis. Liver tissues from mice were assessed by
      histologic analysis; markers of fibrosis were measured by quantitative polymerase
      chain reaction (qPCR). Reverse transcription PCR detected changes in expression
      of the microRNA miR132 and its target, elongated transcripts of MeCP2.
      Myofibroblasts were transfected with miR132; PPARgamma and MeCP2 expressions were
      analyzed by qPCR or immunoblotting. RESULTS: Myofibroblast transdifferentiation
      of hepatic stellate cells is controlled by a combination of MeCP2, EZH2, and
      miR132 in a relay pathway. The pathway is activated by down-regulation of miR132,
      releasing the translational block on MeCP2. MeCP2 is recruited to the 5' end of
      PPARgamma, where it promotes methylation by H3K9 and recruits the transcription
      repressor HP1alpha. MeCP2 also stimulates expression of EZH2 and methylation of
      H3K27 to form a repressive chromatin structure in the 3' exons of PPARgamma.
      Genetic and pharmacologic disruptions of MeCP2 or EZH2 reduced the fibrogenic
      characteristics of myofibroblasts and attenuated fibrogenesis. CONCLUSIONS: Liver
      fibrosis is regulated by an epigenetic relay pathway that includes MeCP2, EZH2,
      and miR132. Reagents that interfere with this pathway might be developed to
      reduce fibrogenesis in chronic liver disease.

PMID- 19843475
TI  - Diffusion tensor imaging supports the cytotoxic origin of brain edema in a rat
      model of acute liver failure.
AB  - BACKGROUND & AIMS: Brain edema is a severe complication of acute liver failure
      (ALF) that has been related to ammonia concentrations. Two mechanisms have been
      proposed in the pathogenesis: vasogenic edema that is secondary to the breakdown
      of the blood-brain barrier and cytotoxic edema caused by ammonia metabolites in
      astrocytes. METHODS: We applied magnetic resonance techniques to assess the
      intracellular or extracellular distribution of brain water and metabolites in a
      rat model of devascularized ALF. The brain water content was assessed by
      gravimetry and blood-brain barrier permeability was determined from the transfer
      constant of (14)C-labeled sucrose. RESULTS: Rats with ALF had a progressive
      decrease in the apparent diffusion coefficient (ADC) in all brain regions. The
      average decrease in ADC was significant in precoma (-14%) and coma stages (-20%).
      These changes, which indicate an increase of the intracellular water compartment,
      were followed by a significant increase in total brain water (coma 82.4% +/- 0.3%
      vs sham 81.6% +/- 0.3%; P = .0001). Brain concentrations of glutamine (6 hours,
      540%; precoma, 851%; coma, 1086%) and lactate (6 hours, 166%; precoma, 998%;
      coma, 3293%) showed a marked increase in ALF that paralleled the decrease in ADC
      and neurologic outcome. In contrast, the transfer constant of (14)C-sucrose was
      unaltered. CONCLUSIONS: The pathogenesis of brain edema in an experimental model
      of ALF involves a cytotoxic mechanism: the metabolism of ammonia in astrocytes
      induces an increase of glutamine and lactate that appears to mediate cellular
      swelling. Therapeutic measures should focus on removing ammonia and improving
      brain energy metabolism.

PMID- 19843476
TI  - Time to fixation in the presence of recombination.
AB  - We study the evolutionary dynamics of a haploid population of infinite size
      recombining with a probability r in a two locus model. Starting from a low
      fitness locus, the population is evolved under mutation, selection and
      recombination until a finite fraction of the population reaches the fittest
      locus. An analytical method is developed to calculate the fixation time T to the
      fittest locus for various choices of epistasis. We find that: (1) for negative
      epistasis, T decreases slowly for small r but decays fast at larger r; (2) for
      positive epistasis, T increases linearly for small r and mildly for large r; (3)
      for compensatory mutation, T diverges as a power law with logarithmic corrections
      as the recombination fraction approaches a critical value. Our calculations are
      seen to be in good agreement with the exact numerical results.

PMID- 19843477
TI  - Fluctuation domains in adaptive evolution.
AB  - We derive an expression for the variation between parallel trajectories in
      phenotypic evolution, extending the well known result that predicts the mean
      evolutionary path in adaptive dynamics or quantitative genetics. We show how this
      expression gives rise to the notion of fluctuation domains-parts of the fitness
      landscape where the rate of evolution is very predictable (due to fluctuation
      dissipation) and parts where it is highly variable (due to fluctuation
      enhancement). These fluctuation domains are determined by the curvature of the
      fitness landscape. Regions of the fitness landscape with positive curvature, such
      as adaptive valleys or branching points, experience enhancement. Regions with
      negative curvature, such as adaptive peaks, experience dissipation. We explore
      these dynamics in the ecological scenarios of implicit and explicit competition
      for a limiting resource.

PMID- 19843478
TI  - Differential regulation of MAP kinase activation by a novel splice variant of
      human MAP kinase phosphatase-2.
AB  - MAP kinase phosphatase-2 (MKP-2) is a member of the family of dual specificity
      phosphatases that functions to inactivate the ERK and JNK MAP kinase signalling
      pathways. Here, we identify a novel human MKP-2 variant (MKP-2-S) lacking the MAP
      kinase binding site but retaining the phosphatase catalytic domain. Endogenous
      MKP-2-S transcripts and proteins were found in PC3 prostate and MDA-MB-231 breast
      cancer cells and also human prostate biopsies. Cellular transfection of MKP-2-S
      gave rise to a nuclear protein of 33kDa which displayed phosphatase activity
      comparable to the formerly described long form of MKP-2 (MKP-2-L). Due to its
      lack of a kinase interacting motif (KIM), MKP-2-S did not bind to JNK or ERK; MKP
      2-L bound ERK and to a lesser extent JNK. Protein turnover of adenoviral
      expressed MKP-2-S was accelerated relative to MKP-2-L, with a greater
      susceptibility to proteosomal-mediated degradation. MKP-2-S retained its ability
      to deactivate JNK in a similar manner as MKP-2-L and was an effective inhibitor
      of LPS-stimulated COX-2 induction. However, unlike MKP-2-L, MKP-2-S was unable to
      reverse serum-induced ERK activation or significantly inhibit endothelial cell
      proliferation. These findings reveal the occurrence of a novel splice variant of
      MKP-2 which is unable to bind ERK and may be significant in the dysregulation of
      MAP kinase activity in certain disease states, particularly in breast and
      prostate cancers.

PMID- 19843479
TI  - Five novel antimicrobial peptides from skin secretions of the frog, Amolops
      loloensis.
AB  - While investigating antimicrobial peptide diversity of Amolops loloensis, five
      novel antimicrobial peptides belonging to two families were identified from skin
      secretions of this frog. The first family including two members is esculentin-2
      AL (esculentin-2-ALa and -ALb); the second family including three members is
      temporin-AL (temporin-ALd to -ALf). The family of esculentin-2-AL is composed of
      37 amino acid residues (aa); the family of temporin-AL is composed of 16, 13 and
      10 aa, respectively. All of these antimicrobial peptides showed antimicrobial
      activities against tested microorganisms. cDNAs encoding precursors of esculentin
      2-ALs and temporin-ALs were cloned from the skin cDNA library of A. loloensis.
      All the precursors share similar overall structures. There is a typical
      prohormone processing signal (Lys-Arg) located between the acidic propiece and
      the mature peptide. The antimicrobial peptide family of esculentin-2 is firstly
      reported in the genus of Amolops. Combined with previous reports, a total of four
      antimicrobial peptide families have been identified from the genus of Amolops;
      three of them are also found in the genus of Rana. These results suggest the
      possible evolutionary connection between the genera Amolops and Rana.

PMID- 19843480
TI  - Romiplostim in chronic immune thrombocytopenic purpura.
AB  - BACKGROUND: Immune thrombocytopenic purpura (ITP) is characterized by platelet
      deficiency due to platelet destruction and/or inadequate production. Initial
      therapy consists of corticosteroids or intravenous immunoglobulin (IVIg).
      Patients with chronic refractory disease might undergo splenectomy. Although
      there is no treatment of choice in those who do not respond to splenectomy,
      immunosuppressive agents are typically prescribed. Romiplostim is the first
      available drug in a recently developed class of agents that work through
      stimulation of the thrombopoietin (TPO) receptor (c-Mpl) to increase platelet
      production. OBJECTIVE: The aim of this report was to review the mechanism of
      action, pharmacology, clinical activity, and adverse events associated with the
      use of romiplostim for the treatment of thrombocytopenia in patients with chronic
      ITP. METHODS: MEDLINE, Google Scholar, International Pharmaceutical Abstracts,
      and Web of Science were searched for English-only clinical trials and reviews
      (publication dates: 2000-June 1, 2009; key terms: romiplostim, Nplate, ITP, and
      idiopathic and immune thrombocytopenic purpura). Abstracts from the 2000-2008
      meetings of the American Society of Hematology and references from relevant
      articles were reviewed. RESULTS: A total of 6 studies were included. Romiplostim
      is the first marketed agent developed to directly stimulate the bone marrow to
      produce platelets. Produced in Escherichia coli using recombinant DNA technology,
      it is an Fc-peptide fusion protein. It works intracellularly in a manner similar
      to that of the naturally occurring TPO to activate the transcriptional pathways,
      leading to increased platelet production via stimulation of the c-Mpl receptor.
      Romiplostim was approved by the US Food and Drug Administration for the treatment
      of chronic ITP primarily based on the findings from 2 multicenter, randomized,
      placebo-controlled, parallel-group studies in 125 adult patients with chronic ITP
      and an insufficient response to corticosteroids, IVIg, and/or splenectomy. The
      most common prior treatments were corticosteroids (94%) and IVIg (80%). Sixty
      three patients (50%) were splenectomized a median of 6.6 years earlier. Baseline
      platelet counts were <30 x 10(9) cells/L. The initial dose of romiplostim was 1
      microg/kg/wk SC, with adjustments to maintain platelet counts between 50 and 200
      x 10(9) cells/L. The primary end point was a durable platelet response (>or=50 x
      10(9) cells/L for >or=6 of the last 8 weeks of treatment). The proportion of
      patients in whom a durable platelet response was achieved was significantly
      greater with romiplostim than with placebo (49% vs 2%, respectively; P < 0.001).
      Overall platelet responses (durable plus transient) were achieved in 83% (69/83)
      with romiplostim and 7% (3/42) with placebo (P < 0.001). An interim report of
      findings from an ongoing extension study found that response was maintained for
      up to 156 weeks (median, 69 weeks) with romiplostim. The most common adverse
      events were headache (37%), nasopharyngitis (32%), contusion (30%), epistaxis
      (30%), fatigue (30%), arthralgia (25%), and diarrhea (25%). CONCLUSIONS: Based on
      the findings from this review, romiplostim administration has been associated
      with a durable platelet response in these patients with refractory chronic ITP.
      Romiplostim has been found to be generally well tolerated.

PMID- 19843481
TI  - Time to onset and duration of action of the antihistamine bepotastine besilate
      ophthalmic solutions 1.0% and 1.5% in allergic conjunctivitis: a phase III,
      single-center, prospective, randomized, double-masked, placebo-controlled,
      conjunctival allergen challenge assessment in adults and children.
AB  - BACKGROUND: Bepotastine besilate is a highly selective histamine H(1)-receptor
      antagonist with antihistaminic, mast cell stabilizing, and anti-inflammatory
      activity. Based on a history of clinical effectiveness and tolerability of oral
      bepotastine besilate in the treatment of allergic symptoms, bepotastine besilate
      is being tested as a potential ophthalmic medication for allergic conjunctivitis.
      OBJECTIVE: The aim of this study was to assess the effects of bepotastine
      besilate ophthalmic solution 1.0% and 1.5% for the treatment of ocular itching
      and conjunctival hyperemia in a conjunctival allergen challenge (CAC) model in
      adults and children. METHODS: This Phase III, single-center, prospective,
      randomized, double-masked, placebo-controlled, CAC clinical trial enrolled
      patients >or=10 years of age with a history of allergic conjunctivitis, skin-test
      reaction, and CAC response. Patients received bepotastine besilate ophthalmic
      solution 1.0%, bepotastine besilate ophthalmic solution 1.5%, or placebo, 1 drop
      on each eye on days 14 +/- 3 and 28 +/- 3. The primary efficacy end points,
      patient-assessed ocular itching (at 3, 5, and 7 minutes) and investigator
      assessed conjunctival hyperemia (at 7, 15, and 20 minutes), were determined after
      CAC according to standardized 5-point scales (0 = none to 4 = severe). Clinical
      significance was defined in the protocol as >or=1.0-U between-group difference in
      mean ocular itching scores at the majority of time points at a study visit and
      also a >or=0.5-U difference at all time points. Tolerability of the test agent
      was assessed by visual acuity, slit-lamp biomicroscopy, intraocular pressure,
      dilated funduscopy, and adverse events. RESULTS: A total of 107 patients (male,
      54%; age range, 11-73 years; white race/ethnicity, 93%) received investigational
      product and comprised the intent-to-treat (ITT) population (bepotastine besilate
      ophthalmic solution 1.0%, 36 patients; bepotastine besilate ophthalmic solution
      1.5%, 35; and placebo, 36). All 107 patients received investigational product at
      visit 3A (day 0) and were included in the ITT population. Of the 107 patients who
      were enrolled, 103 completed the study without a protocol deviation or violation.
      The 1.0% and 1.5% solutions were associated with clinically and statistically
      significant reductions in mean ocular itching scores compared with placebo on the
      15-minute onset-of-action and 8-hour duration-of-action CAC tests (reductions,
      1.3-1.5 U and 1.0-1.7 U respectively; all, P < 0.001). Statistically significant
      reductions in conjunctival hyperemia were achieved with both bepotastine besilate
      concentrations. Overall, 13 patients experienced a treatment-emergent adverse
      event considered related to the study drug (bepotastine besilate ophthalmic
      solution 1.0%, 6 patients; bepotastine besilate ophthalmic solution 1.5%, 4; and
      placebo, 3). CONCLUSIONS: In this CAC model of allergic conjunctivitis in adults
      and children, bepotastine besilate ophthalmic solutions 1.0% and 1.5% were
      associated with clinically and statistically significant reductions in ocular
      itching, but not conjunctival hyperemia, within 15 minutes that were maintained
      for at least 8 hours after administration. Both solutions were well tolerated.
      ClinicalTrials.gov identifier: NCT00424398.

PMID- 19843482
TI  - A multicenter, randomized, double-blind, placebo-controlled trial of intravenous
      ibuprofen 400 and 800 mg every 6 hours in the management of postoperative pain.
AB  - BACKGROUND: Although opioids are the mainstay of inpatient postoperative pain
      management, they do not block inflammation. The NSAID ibuprofen has
      antiinflammatory and analgesic properties, and a multimodal approach may reduce
      opioid requirements. OBJECTIVE: This study was conducted to assess the effects of
      intravenously administered ibuprofen 400 and 800 mg q6h in postoperative pain
      management. METHODS: This multicenter, randomized, double-blind, placebo
      controlled trial was conducted in 406 patients scheduled to undergo elective,
      single-site orthopedic or abdominal surgery. All patients received morphine
      administered by patient-controlled analgesia pump, or by hospital staff at the
      request of the patient, after surgery and were randomly assigned in a 1:1:1 ratio
      to receive ibuprofen 400 mg IV, ibuprofen 800 mg IV, or inactive vehicle
      (placebo). The first dose of study drug was administered intraoperatively at the
      initiation of wound closure, then every 6 hours for a total of 8 doses over the
      first 48 hours of the study. After the initial 8 doses, the protocol allowed for
      continued administration of IV ibuprofen or placebo every 6 hours, at the
      discretion of the investigator, for control of postoperative pain for a total of
      up to 120 hours (5 days). The ibuprofen and placebo were administered while
      patients had access to morphine throughout the duration of the study. The primary
      outcome measure was morphine use in the first 24 hours after surgery. Secondary
      measures were patient self-reports of pain scores at rest and with movement. Pain
      intensity was measured before (baseline) and at 1, 2, 3, 6, 9, 12, 15, 18, 24,
      27, 30, 33, 36, 39, 42, 45, and 48 hours after the first administration of study
      medication, and then once daily through day 5 if the patient continued to receive
      study medication. Patients were assessed by study personnel for treatment
      emergent adverse events (AEs). RESULTS: A total of 406 patients were enrolled
      (319 women, 87 men; mean [SD] age, 45 [12] years; weight, 83.8 [19.1] kg;
      ibuprofen 400 mg IV, 134 patients; ibuprofen 800 mg IV, 138; and placebo, 134).
      In the intent-to-treat population, median morphine use was significantly reduced
      during the first 24 hours after administration of the study drug in patients who
      received ibuprofen 800 mg IV q6h (by 22% vs placebo; P = 0.030). The use of
      ibuprofen 800 mg IV q6h was associated with significant reductions in pain at
      rest and with movement across 3 time periods (1-24, 6-24, 12- 24 hours) compared
      with placebo. Ibuprofen 400 mg IV q6h was associated with significant reductions
      in pain at rest and with movement during the 6- to 24-hour and 12- to 24-hour
      time periods compared with placebo. The prevalences of AEs and abnormalities in
      laboratory measurements were not significantly different between patients who
      received IV ibuprofen and those who received placebo. Treatment-emergent AEs were
      reported in 368 of 406 patients (91%). With respect to the number of patients who
      experienced serious AEs, the differences in the 400-mg IV ibuprofen group
      (118/134 [88%]) and the 800-mg IV ibuprofen group (124/138 [90%]) compared with
      the placebo group (126/134 [94%]) were not statistically significant. There were
      significant reductions in the proportions of patients who experienced
      gastrointestinal disorders in the 400- and 800-mg IV ibuprofen groups compared
      with the placebo group (99/134 [74%] and 98/138 [71%], respectively, vs 113/134
      [84%]; P = 0.05 and P = 0.009). There were significant reductions in the numbers
      of patients experiencing pyrexia in the 400- and 800-mg IV ibuprofen groups
      compared with the placebo group (9/134 [7%] and 10/138 [7%] vs 23/134 [17%]; P =
      0.013 and P = 0.015). Dizziness occurred in a significantly greater proportion of
      patients in the ibuprofen 800-mg q6h group compared with the placebo group (P =
      0.011). CONCLUSIONS: In these patients undergoing postoperative pain management,
      ibuprofen 800 mg IV q6h was associated with significant reductions in morphine
      use and pain at rest and with movement compared with placebo. Ibuprofen IV was
      not associated with significant increases in AEs compared with placebo, with the
      exception of dizziness with the 800-mg dose. These findings suggest that
      ibuprofen 800 mg IV q6h was effective for postoperative pain management and was
      generally well tolerated. ClinicalTrials.gov identifier: NCT00225732.

PMID- 19843483
TI  - Clinical outcomes of patients receiving daptomycin for the treatment of
      Staphylococcus aureus infections and assessment of clinical factors for
      daptomycin failure: a retrospective cohort study utilizing the Cubicin Outcomes
      Registry and Experience.
AB  - BACKGROUND: Daptomycin is most commonly used as a second-line treatment. Previous
      studies have not differentiated the effect of prior antibiotic therapy on
      daptomycin clinical outcomes. OBJECTIVES: The primary objective of this study was
      to compare clinical outcomes of patients treated with daptomycin as first-line
      therapy versus after prior antibiotic therapy (specifically, vancomycin). A
      secondary objective was to identify other factors associated with the clinical
      failure of daptomycin therapy. METHODS: This was a retrospective cohort study
      using data from a postlabeling registry database. The effects of relevant patient
      characteristics on the clinical outcome of individuals treated for Staphylococcus
      aureus infections with daptomycin were examined in an unblinded approach using
      univariate and multivariate analyses. Only patients with an evaluable clinical
      outcome (ie, cure, improvement, failure) and culture-confirmed S aureus infection
      were included in the analysis cohort. RESULTS: Of 1227 clinically evaluable
      patients, 250 (20%) received daptomycin as first-line therapy and 977 (80%)
      received daptomycin after other prior antibiotic therapy. Overall, 53% of
      patients were male; 64% were aged 31 to 65 years and 26% were aged >or=66 years.
      Race information was collected beginning in 2007; of the patients studied, 71%
      were white and 18% were black. The initial daptomycin dose (mean [SD]) overall
      was 5.1 (1.1) mg/kg and was highest for patients with endocarditis (5.9 [1.2]
      mg/kg) and lowest for those with uncomplicated skin and skin structure infections
      (4.4 [0.9] mg/kg). Clinical success, defined as an outcome of cured or improved
      at the end of daptomycin therapy, was reported for 1140 (93%) of the 1227
      evaluable patients. The clinical success rates for first-line therapy with
      daptomycin and after prior antibiotics were both 93%. Using univariate analysis,
      8 variables were associated with clinical failure (receipt of daptomycin in an
      intensive care unit setting, severe renal dysfunction [creatinine clearance <30
      mL/min], dialysis, diabetes mellitus (DM), concomitant antibiotics, bacteremia,
      endocarditis, and failure of prior vancomycin therapy) and 3 with clinical
      success (outpatient daptomycin therapy and complicated and uncomplicated skin and
      skin structure infections). Using the stepwise multivariate regression analysis,
      only the presence of endocarditis (odds ratio [OR] = 2.56; 95% CI, 1.18-5.54; P =
      0.017), bacteremia (OR = 1.77; 95% CI, 1.04-3.02; P = 0.037), severe renal
      dysfunction (OR = 1.78; 95% CI, 1.05-3.03; P = 0.034), and DM (OR = 1.79; 95% CI,
      1.10-2.93; P = 0.02) were identified as factors independently associated with
      clinical failure of daptomycin therapy. Of the remaining patients, 9% were aged
      18 to 30 years and 0.7% were aged 12 to 17 years. CONCLUSIONS: In this
      retrospective study, after controlling for clinical factors that are associated
      with suboptimal outcomes, clinical outcomes with daptomycin did not differ
      whether it was used as first-line therapy or after other antibiotics.
      Endocarditis, bacteremia, severe renal dysfunction, and DM were associated with
      higher rates of clinical failure of daptomycin treatment.

PMID- 19843484
TI  - Efficacy and tolerability of nebivolol monotherapy by baseline systolic blood
      pressure: a retrospective analysis of pooled data from two multicenter, 12-week,
      randomized, double-blind, placebo-controlled, parallel-group, dose-ranging
      studies in patients with mild to moderate essential hypertension.
AB  - BACKGROUND: In clinical studies, nebivolol at doses of 2.5 to 40 mg once daily
      was associated with significant decreases in systolic blood pressure (SBP) and
      diastolic BP (DBP) in patients with hypertension and was well tolerated.
      OBJECTIVES: This post hoc analysis of pooled data from 2 previously published
      registration studies was conducted to further evaluate the antihypertensive
      efficacy and tolerability of nebivolol in patients with mild to moderate (stage 1
      2) hypertension. METHODS: The 2 trials were similarly designed multicenter, 12
      week, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging
      studies in patients 18 years of age and older with stage 1 or 2 hypertension (SBP
      140-159 mm Hg and/or DBP 90-99 mm Hg [stage 1] or SBP >or= 160 mm Hg and/or DBP
      >or= 100 mm Hg [stage 2]). The primary efficacy end point of the 2 studies was
      the change from baseline in mean trough SiDBP at week 12. A secondary end point
      was the change from baseline to week 12 in mean trough sitting SBP (SiSBP). The
      present analysis included only patients who received nebivolol 5, 10, or 20 mg
      (the doses were common to both studies) or placebo, including analyses stratified
      by baseline SBP, although DBP represented a criterion for entry into the studies.
      Baseline SBP stratification levels were 140 to 149 mm Hg, 150 to 159 mm Hg, 160
      to 169 mm Hg, and 170 to 179 mm Hg. For the tolerability analysis, the
      prevalences of treatment-emergent adverse events (AEs) were compared between the
      3 nebivolol dose groups and the placebo group. RESULTS: Of the 1716 randomized
      patients who received study medication in the 2 trials, data from 1385 patients
      were included in this pooled analysis (759 men, 626 women; median age, ~54 years;
      13.6% black). Mean (SD) baseline SiSBP and SiDBP values were 151.9 to 152.7 and
      99.2 to 99.5 mm Hg, respectively. Reductions from baseline in trough SiSBP were 
      10.8 (13.5), -10.7 (14.7), and -12.4 (15.5) mm Hg with nebivolol 5, 10, and 20
      mg, respectively, compared with -4.5 (13.4) mm Hg with placebo (all, P < 0.001).
      Reductions from baseline in trough SiDBP (the primary end point) were -9.8 (7.9),
      -10.5 (8.2), and -11.1 (8.6) mm Hg with nebivolol 5, 10, and 20 mg, respectively,
      compared with -5.1 (8.1) mm Hg with placebo (all, P < 0.001). In a subgroup of
      1227 patients stratified by baseline SBP, the reductions in SBP and DBP were
      significantly greater (P < 0.03 and P < 0.001, respectively) with nebivolol at
      each dose compared with placebo in those with baseline SBP of 140 to 149 mm Hg
      and 150 to 159 mm Hg (the lowest 2 baseline strata); in the highest 2 baseline
      strata (SBP 160-169 and 170-179 mm Hg), the reductions in SBP with nebivolol 5 mg
      and nebivolol 20 mg in the 160 to 169-mm Hg baseline SBP stratum and in DBP with
      nebivolol 20 mg in the 170 to 179-mm Hg baseline stratum were significantly
      greater (P < 0.03) compared with placebo. The most common AE in the nebivolol 5-,
      10-, and 20-mg groups and the placebo group was headache (36/409 [8.8%], 25/410
      [6.1%], 27/410 [6.6%], and 10/156 [6.4], respectively), followed by fatigue
      (9/409 [2.2%], 10/410 [2.4%], 25/410 [6.1%], and 3/156 [1.9%]) and dizziness
      (6/409 [1.5%], 9/410 [2.2%], 15/410 [3.7%], and 4/156 [2.6%]). CONCLUSION: The
      present analysis of pooled data from 2 previously published registration studies
      found that nebivolol was associated with significant reductions in BP compared
      with placebo in these patients with stage 1 or 2 hypertension, with a
      tolerability similar to that of placebo.

PMID- 19843485
TI  - Prediction of abstinence at 10 weeks based on smoking status at 2 weeks during a
      quit attempt: secondary analysis of two parallel, 10-week, randomized, double
      blind, placebo-controlled clinical trials of 21-mg nicotine patch in adult
      smokers.
AB  - BACKGROUND: Smoking cessation outcomes are calculated as the probability of
      abstinence at follow-up among all enrolled smokers, but it is also useful to
      estimate the probability of success for those who experienced success or failure
      at earlier time points. OBJECTIVES: The primary aims were to estimate the
      probability of maintaining abstinence through week 10 among subjects who were
      abstinent at week 2, and to assess the effect of active treatment with a nicotine
      patch. We also examined outcomes at week 6 and, among subjects who smoked during
      the first 2 weeks of treatment, the probability of reestablishing abstinence
      later, as well as the effect of active treatment on this outcome. METHODS: We
      analyzed pooled data from 2 previously published, parallel, double-blind studies
      in which subjects were initially randomized to receive an active nicotine patch
      (starting at 21 mg) or a placebo patch. Subjects randomized to active treatment
      followed a double-blind step-down dosing regimen: 24-h/21-mg patches for the
      first 6 weeks of treatment, followed by 14- and 7-mg patches for successive 2
      week periods. Biochemically verified abstinence (exhaled carbon monoxide <or=8
      ppm) was assessed during laboratory visits. RESULTS: Most subjects were white
      (94.8%) and female (61.6%), with a mean (SD) age of 43.1 (10.2) years. Subjects
      had been smoking for a mean of 24.5 (10.2) years and smoked a mean of 30.6 (10.4)
      cigarettes per day. In both the nicotine (n = 249) and placebo (n = 253) groups,
      all subjects who were abstinent during the first 2 weeks had a high probability
      of maintaining abstinence through week 10, but subjects treated with the active
      patch were significantly more likely to remain abstinent (active: 79.8% [67/84],
      placebo: 52.6% [20/38]; relative risk [RR] = 1.52 [95% CI, 1.10-2.09]). Also, at
      week 6, subjects receiving active treatment had a greater chance of remaining
      abstinent (active: 94.3% [82/87], placebo: 78.0% [32/41]; RR = 1.21 [95% CI, 1.02
      1.43]). To assess the effect of treatment on recovery from smoking lapses, we
      examined the probability of abstinence during week 10 among subjects who smoked
      during the first 2 weeks of treatment. Among them, treatment was associated with
      a greater probability of later success: 31.4% (50/159) of those treated with the
      active patch and 12.5% (26/208) of those receiving placebo were abstinent at week
      10 (RR = 2.52 [95% CI, 1.64-3.85]). Similar results were observed at week 6
      (49.4% [80/162] vs 21.2% [45/212]; RR = 2.33 [95% CI, 1.72-3.15]). CONCLUSIONS:
      More than two thirds (71.3%) of subjects who were abstinent 2 weeks into a quit
      attempt maintained that abstinence through the end of 10 weeks of treatment. Use
      of a nicotine patch was significantly associated with maintaining abstinence and
      with recovering abstinence after an early lapse.

PMID- 19843486
TI  - Effect of agalsidase alfa replacement therapy on Fabry disease-related
      hypertrophic cardiomyopathy: a 12- to 36-month, retrospective, blinded
      echocardiographic pooled analysis.
AB  - BACKGROUND: Fabry disease is an X-linked disease caused by a deficiency in the
      activity of the lysosomal enzyme alpha-galactosidase A. Affected individuals
      typically develop left ventricular hypertrophy (LVH) among other pathologies.
      OBJECTIVE: The purpose of the present study was to investigate the effect of
      >or=12 months of enzyme replacement therapy (ERT) with agalsidase alfa on LV mass
      (LVM) in men and women with Fabry disease. METHODS: This was a retrospective,
      blinded, pooled analysis of data from several studies assessing the effect of ERT
      with agalsidase alfa on LVM in patients with Fabry disease with baseline LVH. Men
      and women aged >or=18 years with a confirmed diagnosis of Fabry disease who had
      received >or=36 months of ERT with agalsidase alfa were eligible, provided they
      had a baseline echocardiogram and a follow-up echocardiogram at 12 and/or 36
      months. Data from 4 studies were included in the present analysis. LVM was
      normalized to height (in meters) to the 2.7 power (LVM/h = LVM/m(2.7)). RESULTS:
      In total, 45 adult patients (34 men and 11 women) with a confirmed diagnosis of
      Fabry disease and serial echocardiograms obtained at baseline and after 12 and/or
      36 months of treatment were included. The mean (SD) age of this cohort was 39.8
      (10.4) years (range, 18.9-67.2 years), and the mean weight was 72.5 (13.4) kg
      (range, 46.7-102.9 kg). Forty-two patients were white, 2 were Hispanic, and 1 was
      classified as other. At baseline, 14 patients had LVH (mean LVM/h = 55.4 [5.7]
      g/m(2.7)). After 12 months of ERT with agalsidase alfa, LVM/h decreased
      significantly by 9.2 (7.9) g/m(2.7) in 9 patients (P = 0.008), and after 36
      months, LVM/h decreased significantly by 5.1 (7.5) g/m(2.7) in 10 patients (P =
      0.037). In patients without baseline LVH (n = 31), a significant increase in
      LVM/h was observed after 12 months of treatment (3.6 [5.7] g/m(2.7); P = 0.002).
      After 36 months of treatment, however, there was no significant change from
      baseline in 10 patients (2.1 [7.9] g/m(2.7); P = NS). CONCLUSION: Treatment with
      agalsidase alfa for 12 or 36 months was associated with reduced LVM in these
      patients with Fabry disease with baseline LVH, and it appeared to stabilize LVM
      in these patients without baseline LVH.

PMID- 19843487
TI  - Tolerability of teicoplanin in 117 hospitalized adults with previous vancomycin
      induced fever, rash, or neutropenia: a retrospective chart review.
AB  - BACKGROUND: Vancomycin has reliable antibacterial activity against many gram
      positive pathogens but is associated with many adverse events. Teicoplanin,
      another glycopeptide, is associated with fewer adverse events, but its use in
      patients with previous vancomycin-induced adverse reactions remains
      controversial. OBJECTIVES: The aims of this work were to evaluate the clinical
      characteristics of hospitalized patients with vancomycin-induced fever (ie, drug
      fever), rash, or neutropenia and to examine the tolerability of teicoplanin in
      these patients. METHODS: This was a retrospective review of the medical charts of
      patients aged >or=18 years who were hospitalized between January 2002 and October
      2007 at National Cheng Kung University Hospital in Tainan, Taiwan. Patients were
      included if they experienced drug-induced fever (ie, "drug fever"), rash, or
      neutropenia during vancomycin treatment. Their antimicrobial therapy was
      subsequently switched to teicoplanin. Clinical information and the development of
      drug fever, rash, or neutropenia with teicoplanin were determined from the
      charts. RESULTS: Antibiotic therapy was switched to teicoplanin in 117 patients
      with vancomycin-induced fever alone (n = 24), rash alone (n = 77), both drug
      fever and rash (n = 8), or neutropenia (n = 8). The mean (SD) age of these
      patients was 53.1 (22.8) years, and 65 (56%) were male. The major clinical
      indications for vancomycin therapy among these patients were wound infections
      (21%), respiratory tract infections (14%), and bacteremia (13%). The dosages for
      vancomycin ranged from 1 g every 5 days to 1 g BID, and for teicoplanin ranged
      from 400 mg daily to 400 mg q72h, adjusted by the degree of renal dysfunction.
      Overall, 12 patients with vancomycin-induced fever (n = 2), rash (n = 6), or
      neutropenia (n = 4) subsequently developed teicoplanin-induced fever (n = 3),
      rash (n = 3), or neutropenia (n = 6). Specifically, of 8 patients with vancomycin
      induced neutropenia, 4 (50%) subsequently developed neutropenia after switching
      to teicoplanin. Vancomycin- and teicoplanin-induced neutropenia was often noted
      after 1 week of treatment. Among patients with vancomycin-induced fever, rash, or
      neutropenia, there were no differences between patients with or without
      teicoplanin-induced fever, rash, or neutropenia in terms of age, sex, weight,
      dosage or duration of vancomycin therapy, dosage of teicoplanin, or underlying
      disease. There was no difference in mortality rates between patients with or
      without teicoplanin-induced fever, rash, or neutropenia. The cause of all deaths
      was progression of infectious or underlying disease, unrelated to vancomycin or
      teicoplanin use. CONCLUSIONS: Based on this retrospective chart review of
      hospitalized patients with vancomycin-induced fever, rash, or neutropenia, only
      10% experienced subsequent teicoplanin-induced fever, rash, or neutropenia.
      However, it should be noted that half of the patients with vancomycin-induced
      neutropenia developed teicoplanin-induced neutropenia.

PMID- 19843488
TI  - A case of linear immunoglobulin A bullous dermatosis in a patient exposed to sun
      and an analgesic.
AB  - BACKGROUND: Medications are the most common triggers of linear immunoglobulin A
      bullous dermatosis (LABD). LABD induced by ultraviolet (UV) radiation has rarely
      been described. This article reports a case of LABD in a patient exposed
      simultaneously to an analgesic and UV radiation. CASE SUMMARY: A 45-year-old
      woman developed LABD lesions on sun-exposed skin after 3 days of sunbathing and
      consumption of a medication for headache containing propyphenazone, butalbital,
      and caffeine. The lesions spread to unexposed skin and, by day 5, the patient had
      vesicles and bullae on the palms and soles, face, trunk, and extremities. LABD
      was diagnosed with direct and indirect immunofluorescence microscopy and Western
      blot analysis. Treatment was successful with prednisone, started at a dosage of 1
      mg/kg/d, for 5 months. Lesions located on sun-exposed areas, the absence of
      relapse for 5 years despite continuing sun exposure against medical advice, and
      subsequent avoidance of the suspected medication suggest that the bullous flare
      may have been due to the concomitant action of 2 triggers. That the analgesic had
      a role in this cutaneous manifestation is possible according to the Naranjo
      algorithm for adverse drug reactions. CONCLUSIONS: A case of LABD possibly
      associated with sun exposure and an analgesic is described. Treatment with
      prednisone successfully resolved the lesions in this patient.

PMID- 19843489
TI  - Results of a single-center, single-dose, randomized-sequence, open-label, two-way
      crossover bioequivalence study of two formulations of valsartan 160-mg tablets in
      healthy volunteers under fasting conditions.
AB  - BACKGROUND: Valsartan is a nonpeptide, orally active angiotensin II type 1
      receptor blocker used to treat hypertension alone or in combination with other
      antihypertensive agents. OBJECTIVE: The aim of this study was to compare the
      relative bioavailability of a new valsartan 160-mg formulation (ie, test drug)
      and that of a reference formulation so that bioequivalence could be assessed, as
      required by European regulatory authorities for the marketing of a generic
      product. METHODS: This was a single-center, single-dose, randomized-sequence,
      open-label, 2-way crossover study with a minimum washout period of 7 days; drug
      was administered to healthy volunteers under fasting conditions. Blood samples
      were collected up to 36 hours postadministration, and valsartan levels were
      gauged from plasma by reverse liquid chromatography and tandem mass spectrometry
      detection (ie, the LC-MS/MS method). Pharmacokinetic parameters were calculated
      from valsartan concentration data using noncompartmental analysis. AUC(last),
      AUC(infinity), and C(max) were analyzed. The 90% CIs of the ratios of the test
      versus-reference pharmacokinetic parameters (AUC(last), AUC(infinity), and
      C(max)) were obtained by ANOVA on ln-transformed data. The 90% CIs were required
      to be within 80.00% to 125.00% of the 90% CI to meet the criteria for
      bioequivalence. Tolerability was monitored using physical examination (including
      vital-sign measurements) and ECG performed at screening, as well as laboratory
      analysis, including biochemistry tests, hematology tests, and urinalysis, which
      were performed at screening and during the study period. RESULTS: Thirty-eight
      white (90.5%), 2 black (4.8%), and 2 Hispanic subjects (4.8%) enrolled in the
      study; the sample included a total of 27 men and 15 women. The mean (SD) age was
      37 (11) years and mean weight was 65.4 (7.6) kg. The 90% CI values for
      pharmacokinetic measurements were as follows: AUC(last), 94.45% to 118.59%;
      AUC(infinity), 93.58% to 116.51%; and C(max), 93.61% to 122.02%. Thus, they were
      all within the predefined 80.00% to 125.00% range. Thirty-six postadministration
      adverse events were reported; the most common was blood pressure decrease. A
      decrease of blood pressure was experienced by 6 subjects (14.6%) after the
      administration of the test formulation, and by 5 subjects (12.5%) after the
      administration of the reference formulation. Thirty-three of these adverse events
      were graded as mild and 3 as moderate; 11 were judged as probably related, 12 as
      possibly related, 3 as remotely related, and 10 as unrelated to the study
      medication. CONCLUSIONS: In this open-label study of healthy volunteers, the test
      and reference formulations of valsartan 160 mg met the European regulatory
      definition of bioequivalence, based on the rate and extent of absorption of a
      single dose under fasting conditions. Both formulations were well tolerated.

PMID- 19843490
TI  - A single-dose, three-period, six-sequence crossover study comparing the
      bioavailability of solution, suspension, and enteric-coated tablets of magnesium
      valproate in healthy Mexican volunteers under fasting conditions.
AB  - BACKGROUND: Valproic acid has been associated with a highly variable intersubject
      absorptive phase; therefore, magnesium salt (magnesium valproate [MgV]) was
      developed to diminish variation during enteric absorption. OBJECTIVES: The aims
      of this study were to assess the pharmacokinetics of single oral doses of MgV 500
      mg solution, suspension, and enteric-coated tablets in a healthy Mexican
      population, and to compare formulation-related differences. METHODS: This was a
      randomized, single-dose, 3-period, 6-sequence crossover study in healthy Mexican
      volunteers aged 18 to 45 years. In each period, subjects received single oral
      doses of 500-mg MgV solution, suspension, and enteric-coated tablet formulations,
      with a 7-day washout period between each dosing period. Serial blood samples were
      collected at 0 hour (prior to MgV administration) and at 0.5, 1, 1.5, 2, 2.5, 3,
      3.5, 4, 6, 9, 12, 24, 48, and 72 hours after dosing. Valproate was measured by a
      new method of ultraperformance liquid chromatography coupled with mass
      spectrometry. Pharmacokinetic parameters of interest were C(max), T(max), AUC(0
      72), AUC(0-infinity), t(1/2), V(d)/F, CL/F, and mean residence time (MRT).
      Formulation-related differences were assayed in accordance with the Mexican
      regulatory bioequivalence criteria. Log-transformed values of C(max) and AUC were
      used to construct a classic 90% CI. Bioequivalence was established if the 90% CI
      for the mean test:reference ratio of log-transformed C(max) and AUC were within
      the range of 0.80 to 1.25. Tolerability was assessed based on subject interview,
      vital sign monitoring, and clinical assessment. RESULTS: A total of 24 healthy
      volunteers (12 women and 12 men; mean [SD] age, 28.79 [6.5] years; height, 164
      [9.8] cm; weight, 65.42 [8.95] kg; and body mass index, 24.28 [2.11] kg/m(2))
      were included. For the MgV solution, the mean (SD) pharmacokinetic parameters of
      C(max), T(max), AUC(0-72), AUC(0-infinity), t(1/2), V(d)/F, CL/F, and MRT were
      59.75 (8.24) microg/mL, 0.542 (0.14) hours, 1099.67 (241.70) microg h/mL, 1156.30
      (264.01) microg h/mL, 16.19 (2.36) hours, 9633.68 (1892.70) mL, 418.35 (92.01)
      mL/h, and 18.36 (1.44) hours, respectively. For the MgV suspension, the mean (SD)
      pharmacokinetic parameters of C(max), T(max), AUC(0-72), AUC(0-infinity), t(1/2),
      V(d)/F, CL/F, and MRT were 55.04 (7.72) microg/mL, 0.773 (0.51) hour, 1057.76
      (223.37) microg h/mL, 1111.09 (245.07) microg h/mL, 16.32 (2.20) hours, 1069.05
      (1775.64) mL, 435.43 (99.59) mL/h, and 18.41 (1.43) hours, respectively. For the
      MgV enteric-coated tablets, the mean (SD) pharmacokinetic parameters of C(max),
      T(max), AUC(0-72), AUC(0-infinity), t(1/2), V(d)/F, CL/F, and MRT were 54.88
      (6.73) microg/mL, 2.79 (0.89) hours, 1100.79 (216.70) microg h/mL, 1163.61
      (238.36) microg h/mL, 16.48 (2.10) hours, 9675.15 (1659.36) mL, 412.36 (85.24)
      mL/h, and 19.95 (1.53) hours, respectively. The 90% CIs for the tablets:solution
      ratio were 82.15 to 95.44, 94.60 to 105.39, and 95.43 to 105.95 for C(max), AUC(0
      72), and AUC(0-infinity), respectively. The 90% CIs for the suspension:solution
      ratio were 84.79 to 98.50, 88.89 to 99.02, and 89.15 to 98.97, respectively. The
      90% CIs for the tablets:suspension ratio were 89.90 to 104.43, 100.84 to 112.34,
      and 101.60 to 112.80, respectively. CONCLUSION: This single-dose study found that
      the 3 formulations (solution, suspension, and enteric-coated tablets) of MgV met
      the regulatory criteria for bioequivalence in these healthy, fasting, Mexican
      volunteers.

PMID- 19843491
TI  - Health care reform: is the process the outcome?

PMID- 19843492
TI  - Analysis of the North Carolina long-term care polypharmacy initiative: a multiple
      cohort approach using propensity-score matching for both evaluation and
      targeting.
AB  - BACKGROUND: The high cost and undesirable consequences of polypharmacy are well
      recognized problems among elderly long-term care (LTC) residents. Despite the
      implementation of the 1987 Omnibus Budget Reconciliation Act, which requires
      pharmacist review of drug regimens in this setting, medical and drug costs for
      LTC residents have continued to increase. OBJECTIVE: This study evaluates the
      North Carolina Long-Term Care Polypharmacy Initiative, a large-scale medication
      therapy management program (MTMP) that combined drug utilization review
      activities with drug regimen review techniques. METHODS: This was a prospective
      records-based study that used a difference-in-difference model with both
      historical and nonintervention group controls. To ensure equivalence among
      subjects, propensity scoring was used to match study subjects from participating
      LTC facilities with comparison subjects from nonparticipating facilities.
      Residents with interventions were grouped for analysis by intervention type
      retrospective only, prospective only, or dual type (residents with both
      prospective and retrospective interventions)-and by intervention stage-review,
      recommendation, and drug change-plus an all-inclusive "all types" grouping that
      aggregated groups by intervention type, for a total of 10 total cohorts. RESULTS:
      In the overall population of 5255 study subjects identified, a US $21.63 per
      member per month drug-cost savings was observed. Although only 1 of 10 cohorts
      had a change in the number of drug fills, substantial reductions in 2 of 5 types
      of drug alerts were observed in all 10 cohorts. A reduction in the relative risk
      for hospitalization (0.84 [95% CI, 0.71-1.00]) was observed in the cohort of
      residents receiving a retrospective review. CONCLUSIONS: This Initiative suggests
      that an MTMP can be quickly launched in a large number of LTC facility residents
      to produce monetary drug-cost savings and improved health outcomes. Additionally,
      the evaluation of this program illustrates the utility of using propensity
      scoring techniques to target future intervention groups in a cost-effective
      manner.

PMID- 19843493
TI  - A comparison of aspirin and clopidogrel with or without proton pump inhibitors
      for the secondary prevention of cardiovascular events in patients at high risk
      for gastrointestinal bleeding.
AB  - OBJECTIVE: This study was conducted to compare the risk of recurrent
      hospitalization for major gastrointestinal (GI) complications (peptic ulcer,
      bleeding, and perforation) in patients at high GI risk who require ongoing
      antiplatelet therapy (aspirin [acetylsalicylic acid] or clopidogrel) with or
      without proton pump inhibitors (PPIs). METHODS: This population-based,
      retrospective cohort study employed data from the Taiwanese National Health
      Insurance database (January 2001 through December 2006) for patients who had a
      history of hospitalization for GI complications before the initiation of
      antiplatelet therapy with aspirin or clopidogrel. Recurrent hospitalizations for
      major GI complications were analyzed using a Cox proportional hazards model, with
      adjustment for age, sex, ulcer-related medical history, ulcer-related risk
      factors, and use of ulcer-related medications during follow-up. The propensity
      score method was applied to adjust for selection bias. RESULTS: The analysis
      included data from 14,627 patients (12,001 receiving aspirin, 2626 receiving
      clopidogrel). The incidence of recurrent hospitalization for major GI
      complications was 0.125 per person-year in aspirin users, 0.103 per person-year
      in users of aspirin plus a PPI, 0.128 per person-year in clopidogrel users, and
      0.152 per person-year in users of clopidogrel plus a PPI. Among aspirin users,
      those taking PPIs had a significantly lower adjusted risk of hospitalization for
      major GI complications than did non-PPI users (hazard ratio [HR] = 0.76; 95% CI,
      0.64-0.91). Use of a PPI was not associated with a significant risk reduction
      among clopidogrel users (HR = 1.08; 95% CI, 0.89-1.33). An adjusted survival
      curve for the risk of recurrent hospitalization for major GI complications
      indicated that the risk increased numerically faster in clopidogrel users
      compared with those using aspirin plus a PPI, although the mean drug cost per
      person-year was 5.08 times higher in clopidogrel users than in users of aspirin
      plus a PPI. CONCLUSIONS: In this analysis in patients at high GI risk who were
      receiving antiplatelet therapy for the secondary prevention of cardiovascular
      events, aspirin plus a PPI was associated with a reduced risk of recurrent
      hospitalization for major GI complications. This was not the case for clopidogrel
      plus a PPI.

PMID- 19843494
TI  - Completeness of retail pharmacy claims data: implications for
      pharmacoepidemiologic studies and pharmacy practice in elderly patients.
AB  - BACKGROUND: In the elderly (those aged >or=65 years), retail pharmacy claims are
      used to study drug use among the uninsured after drug policy changes, to prevent
      drug-drug interactions and duplication of therapy, and to guide medication
      therapy management. Claims include only prescriptions filled at 1 pharmacy
      location or within 1 pharmacy chain and do not include prescriptions filled at
      outside pharmacies, potentially limiting research accuracy and pharmacy-based
      safety interventions. OBJECTIVES: The aims of this study were to assess elderly
      patients' pharmacy loyalty and to identify predictors of using multiple
      pharmacies. METHODS: Patients enrolled in the Pharmaceutical Assistance Contract
      for the Elderly (PACE) pharmacy benefit program with corresponding Medicare
      claims in the state of Pennsylvania comprised the study cohort. Among patients
      with pharmacy claims from all pharmacies used in 2004-2005, a primary pharmacy
      was defined as the pharmacy where at least 50% of a patient's prescriptions were
      filled. The number of pharmacies/chains used and prescriptions filled in 2005 was
      calculated. Predictors of using multiple pharmacies in 2005 were age, female
      gender, white race, urban residency, comorbidities, number of distinct chemical
      drugs (unique medications) used, and number of prescriptions filled, which were
      all assessed in 2004. RESULTS: In total, pharmacy claims data from 182,116
      patients (147,718 women [81.1%]; mean [SD] age, 78.8 [7.1] years; 168,175 white
      [92.3%]; 76,580 [42.1%] residing in an urban zip code area) were included. Of the
      182,116 PACE patients in the study, a primary pharmacy was identified for 180,751
      patients (99.3%). In 2005, patients filled an average of 59.3 prescriptions, with
      57.0 prescriptions (96.1%) having been filled at the primary pharmacy. Compared
      with patients who used <or=5 unique medications in 2004, patients who used 6 to 9
      unique medications had 1.38 times (95% CI, 1.34-1.43), and patients who used
      >or=15 unique medications had a 2.66 times (95% CI, 2.53-2.80) greater likelihood
      of using multiple pharmacies in 2005. Patients aged >or=85 years were 1.07 times
      (95% CI, 1.04-1.11) as likely to use multiple pharmacies compared with patients
      aged 65 to 74 years. CONCLUSIONS: This study found that patients aged >or=65
      years were loyal to their primary pharmacy, offering reassurance to researchers
      and pharmacists who use retail pharmacy claims data to evaluate and/or to improve
      safe and appropriate medication use among the elderly. Care should be used in
      analyzing claims or managing the drug regimens of patients using multiple
      medications or patients aged >or=85 years; they are more likely to use multiple
      pharmacies and thus are more likely to have missing prescription information.

PMID- 19843495
TI  - Neuroendocrine tumors (NETs).

PMID- 19843496
TI  - Trends in socioeconomic inequalities in cirrhosis mortality in an urban area of
      Southern Europe: a multilevel approach.
AB  - BACKGROUND: The objective of this study was to analyse inequalities in cirrhosis
      mortality at individual and area levels, using data from Barcelona for two time
      periods. METHODS: Deaths from cirrhosis in Barcelona of men and women aged 25-74
      years during the periods 1992-97 and 1998-2004 were included in the study. A
      multilevel Poisson regression analysis was performed, with the individual and the
      area as the respective units of analysis. RESULTS: Inequalities in cirrhosis
      mortality were observed in relationship to individual and area socioeconomic
      levels, with the highest death rates among those with lowest educational level
      and in socioeconomically deprived areas. In the multilevel analysis, the largest
      effects were observed at the individual level. Between the two periods, death
      rates decreased for the highest and lowest educational levels (eg, from 116.2 to
      88.7 per 100 000 inhabitants among men or men with no education aged 50-74
      years), but not for intermediate levels. At the area level, absolute inequalities
      in mortality tended to decrease; however, higher mortality RR persisted in the
      least favoured compared to most favoured areas (eg, in men, from 1.74 (95% CI
      1.36 to 2.24) to 1.80 (95% CI 1.42 to 2.27) in the two periods). CONCLUSION: This
      study demonstrated the persistence of socioeconomic inequalities in cirrhosis
      mortality in Barcelona between socioeconomic groups and city areas.

PMID- 19843497
TI  - Adverse reproductive and child health outcomes among people living near highly
      toxic waste water drains in Punjab, India.
AB  - BACKGROUND: Environmental influence plays a major role in determining health
      status of individuals. Punjab has been reported as having a high degree of water
      pollution due to heavy metals from untreated industrial effluent discharge and
      high pesticide consumption in agriculture. The present study ascertained the
      association of heavy metal and pesticide exposure on reproductive and child
      health outcomes in Punjab, India. METHODS: A cross-sectional community-based
      survey was conducted in which 1904 women in reproductive age group and 1762
      children below 12 years of age from 35 villages in three districts of Punjab were
      interviewed on a semistructured schedule for systemic and general health
      morbidities. Medical doctors conducted a clinical examination and review of
      records where relevant. Out of 35 study villages, 25 served as target (exposed)
      and 10 as non-target (less exposed or reference). Effluent, ground and surface
      water, fodder, vegetables and milk (bovine and human) samples were tested for
      chemical composition, heavy metals and pesticides. RESULTS: Spontaneous abortion
      (20.6 per 1000 live births) and premature births (6.7 per 1000 live births) were
      significantly higher in area affected by heavy metal and pesticide pollution
      (p<0.05). Stillbirths were about five times higher as compared with a meta
      analysis for South Asian countries. A larger proportion of children in target
      area were reported to have delayed milestones, language delay, blue line in the
      gums, mottling of teeth and gastrointestinal morbidities (p<0.05). Mercury was
      found in more than permissible limits (MPL) in 84.4% samples from the target
      area. Heptachlor, chlorpyriphos, beta-endosulfan, dimethoate and aldrin were
      found to be more than MPL in 23.9%, 21.7%, 19.6%, 6.5% and 6.5% ground water
      samples respectively. CONCLUSION: Although no direct association could be
      established in this study, heavy metal and pesticide exposure may be potential
      risk factors for adverse reproductive and child health outcomes.

PMID- 19843498
TI  - A new method of prenatal alcohol classification accounting for dose, pattern and
      timing of exposure: improving our ability to examine fetal effects from low to
      moderate alcohol.
AB  - BACKGROUND: When examining the association between prenatal alcohol exposure and
      fetal effects, the timing and intensity of exposure have been ignored in
      epidemiological studies. The effect of using dose, pattern and timing of
      consumption ("composite" method) was investigated in this study, to examine the
      association between prenatal alcohol exposure and fetal effects. METHODS: The
      composite method resulted in six categories of exposure (abstinent, low,
      moderate, binge <weekly, binge 1-2*/week and heavy). The odds of language delay
      and child behaviour problems were calculated for the composite method and then
      compared with an analysis using averaged estimates of <1 and 1+ drinks per day
      and with stratification by quantity ignoring dose per occasion. Data used for the
      analyses were from a 10% random sample of non-Indigenous women delivering a live
      infant in Western Australia (1995-1997). Participants from the 1995-1996 cohort
      were invited to participate in an 8 year longitudinal survey (78% response rate
      n=2224; 85% were followed-up at 2 years, 73% at 5 years and 61% at 8 years).
      RESULTS: The effect of moderate and binge levels of exposure was only evident
      with the composite method; anxiety/depression following first-trimester moderate
      exposure (OR 2.24, 95% CI 1.16 to 4.34), and following late pregnancy moderate
      (aggressive behaviour OR 1.93, 95% CI 0.91 to 4.09) and binge (language delay OR
      3.00, 95% CI 0.90 to 9.93) exposures. Results for heavy levels of exposure were
      similar with each method. The estimates for late pregnancy were imprecise due to
      small numbers. Conclusion The composite method of classification more closely
      reflects real-life drinking patterns and better discriminates maternal drinking
      than the other methods, particularly low, moderate and binge levels.

PMID- 19843499
TI  - Sex- and age-specific seasonal variations in physical activity among adults.
AB  - BACKGROUND: To examine seasonal variations in self-reported physical activity
      among an urban population of Calgarian adults. METHOD: Telephone surveys were
      conducted with two independent random cross-sectional samples of adults in summer
      and autumn 2007 (n=2199) and in winter and spring 2008 (n=2223). Participation
      and duration of walking for recreation (WR), walking for transportation (WT),
      moderate (MODPA) and vigorous physical activity (VIGPA) undertaken in a usual
      week were captured. Seasonal comparisons of participation related to these
      activities and sufficient MODPA (>=210 min/week) and VIGPA (>=90 min/week)
      physical activity were examined using logistic regression. RESULTS: Compared with
      winter, participation in WR was significantly (p<0.05) more likely in summer (OR
      1.42), autumn (OR 1.35) and spring (OR 1.40), WT was more likely in autumn (OR
      1.27), and MODPA was more likely in summer (OR 1.42). Achievement of sufficient
      MODPA was significantly more likely in summer (OR 1.80), autumn (OR 1.31) and
      spring (OR 1.24). Although there was no seasonal variation in sufficient VIGPA
      overall, variations in seasonal pattern among sub-populations were observed. Sex-
      and age-specific seasonal patterns in physical activity were also found.
      CONCLUSION: Measuring physical activity throughout the year, rather than at one
      time point, would more accurately monitor physical activity and assist in
      developing seasonally appropriate physical activity interventions. Moreover, in
      countries that experience extreme weather conditions, creating physical activity
      friendly environments that help overcome these conditions might contribute to
      year-long physical activity participation.

PMID- 19843500
TI  - Cranial ultrasound and MRI at term age in extremely preterm infants.
AB  - OBJECTIVES: Conventional MRI at term age has been reported to be superior to
      cranial ultrasound (cUS) in detecting white matter (WM) abnormalities and
      predicting outcome in preterm infants. However, in a previous study cUS was
      performed during the first 6 weeks only and not in parallel to MRI at term age.
      Therefore, the aim of the present work was to study brain injuries in preterm
      infants performing concomitant cUS and MRI at full-term age. METHODS: In a
      population-based cohort of 72 extremely low gestational age infants paired cUS
      and conventional MRI were performed at term age. Abnormalities on MRI were graded
      according to a previously published scoring system. On cUS images the lateral
      ventricles, the corpus callosum, the interhemispheric fissure and the
      subarachnoidal spaces were measured and the presence of cysts, grey matter
      abnormalities and gyral folding were scored. RESULTS: Moderate or severe WM
      abnormalities were detected on MRI in 17% of infants and abnormalities of the
      grey matter in 11% of infants. Among infants with normal ultrasound (n=28, 39%)
      none had moderate or severe WM abnormalities or abnormal grey matter on MRI. All
      infants with severe abnormalities (n=3, 4%) were identified as severe on MRI and
      cUS. CONCLUSIONS: All severe WM abnormalities identified on MRI at term age were
      also detected by cUS at term, providing the examinations were performed on the
      same day. Infants with normal cUS at term age were found to have a normal MRI or
      only mild WM abnormalities on MRI at term age.

PMID- 19843501
TI  - Oxygen delivery using neonatal self-inflating resuscitation bags without a
      reservoir.
AB  - BACKGROUND: Guidelines recommend avoidance of excessive oxygen administration
      during neonatal resuscitation. Blenders are used in some but not all hospitals.
      It has been suggested that self-inflating bags without a reservoir deliver around
      40% oxygen and could be used to provide an inexpensive and effective technique of
      avoiding oxygen toxicity. OBJECTIVE: To explore how much oxygen is delivered when
      using two different brands of neonatal self-inflating resuscitation bags without
      a reservoir. METHODS: In a benchtop setting, the smallest non-disposable self
      inflating bags from the Laerdal and Ambu ranges were tested. Oxygen concentration
      delivered by these devices under a variety of conditions was measured. 108
      combinations of oxygen flow rates (10; 5 to 1 litre/min), ventilation rates (30,
      60, 100 inflations/min) and peak inspiratory pressure ranges (20 to 25 cm H(2)O,
      35 to 40 cm H(2)O or pop-off valve range, 55 to 60 cm H(2)O) were tested.
      RESULTS: Delivered oxygen concentration varied depending on three parameters: gas
      flow rate, ventilatory rate and pressure. At a pressure of 20 to 25 cm H(2)O,
      mean oxygen concentration delivered by both bags exceeded 70% at any gas flow
      rate except for 1 litre/min (where delivered oxygen concentration was 60% to
      70%). When the pop-off valve was opened at 35 to 40 cm H(2)0, oxygen
      concentrations fell to 30% to 45% at gas flow rates < or =2 litres/min. The Ambu
      bag delivered a lower oxygen concentration than the Laerdal bag but this
      difference was not clinically important. CONCLUSION: When using the Laerdal and
      Ambu infant resuscitation self-inflating bags without a reservoir, delivered
      oxygen concentration is >70% for currently recommended flow and pressure
      settings.

PMID- 19843502
TI  - A case of Beckwith-Wiedemann syndrome caused by a cryptic 11p15 deletion
      encompassing the centromeric imprinted domain of the BWS locus.
AB  - BACKGROUND Beckwith-Wiedemann syndrome (BWS) is a clinically variable and
      genetically heterogeneous disorder, providing evidence that imprinted genes play
      key roles in the control of fetal growth. Clinically, diagnostic criteria include
      macrosomia, macroglossia, abdominal wall defects, neonatal hypoglycaemia,
      visceromegalies and hemihyperplasia. Component clinical manifestations also
      include renal abnormalities, adrenocortical cytomegaly and a characteristic
      facial appearance, with midface hypoplasia and ear anomalies. Genetically, BWS is
      associated with disturbances within two different domains on 11p15 that are
      controlled by distinct imprinting control regions (ICR), ICR1 and ICR2. The
      majority of patients have abnormalities within ICR2. In particular, loss of
      maternal methylation accounts for 50-60% of cases, and is associated with
      reduction in the expression of the CDKN1C gene, a member of the cyclin dependent
      kinase inhibitor family acting as negative regulator of cell proliferation.
      Mutations in CDKN1C are detected in another 5-10% of subjects with sporadic BWS.
      Chromosome deletions affecting ICR2 are uncommon. METHODS AND FINDINGS We report
      on a patient with BWS in which a de novo 11p15 deletion was detected by array
      comparative genomic hybridisation. Clinically, the patient presented with mild
      mental retardation and minor physical anomalies. The deletion, that was
      demonstrated to be maternal in origin by SNP array, encompassed ICR2 and several
      flanking genes, including CDKN1C. A normal methylation pattern of ICR1 was
      observed. CONCLUSIONS This observation provides evidence that, among the genetic
      defects associated with BWS, a 11p15 microdeletion encompassing ICR2 identifies a
      peculiar clinical phenotype, with high recurrence risk in offspring of female
      carriers. It also supports the model of two independent domains within the BWS
      locus.

PMID- 19843503
TI  - Clinical and cellular characterisation of Hermansky-Pudlak syndrome type 6.
AB  - BACKGROUND: In the last decade, Hermansky-Pudlak syndrome (HPS) has arisen as an
      instructive disorder for cell biologists to study the biogenesis of lysosome
      related organelles (LROs). Of the eight human HPS subtypes, only subtypes 1
      through 5 are well described. AIM: To characterise extensively the HPS-6 subtype,
      caused by defects in HPS6, a subunit of the biogenesis of lysosome related
      organelles complex-2 (BLOC-2). METHODS: Mutation analysis for the HPS6 gene was
      performed on DNA from our group of unclassified HPS patients. The clinical
      phenotype of patients with HPS6 mutations was then carefully ascertained, and
      their cultured dermal melanocytes were employed for cellular immunofluorescence
      studies. RESULTS: Molecular studies showed a variety of mutations in the single
      exon HPS6 gene, including frame shift, missense, and nonsense mutations as well
      as a approximately 20 kb deletion spanning the entire HPS6 genomic region.
      Cellular studies revealed that the melanogenic proteins tyrosinase and tyrosinase
      related protein 1 failed to be efficiently delivered to the melanosomes of HPS-6
      patients, explaining their hypopigmentation. Clinical studies indicated that HPS
      6 patients exhibit oculocutaneous albinism and a bleeding diathesis. Importantly,
      granulomatous colitis and pulmonary fibrosis, debilitating features present in
      HPS subtypes 1 and 4, were not detected in our HPS-6 patients. CONCLUSION: The
      HPS-6 subtype resembles other BLOC-2 defective subtypes (that is, HPS-3 and HPS
      5) in its molecular, cellular and clinical findings. These findings are not only
      important for providing a prognosis to newly diagnosed HPS-6 patients, but also
      for further elucidation of HPS function in the biogenesis of LROs.

PMID- 19843504
TI  - Renal tumour suppressor function of the Birt-Hogg-Dube syndrome gene product
      folliculin.
AB  - BACKGROUND: Renal cell carcinoma (RCC) comprises five major molecular and
      histological subtypes. The Birt-Hogg-Dube (BHD) syndrome is a hereditary human
      cancer syndrome that predisposes affected individuals to develop renal carcinoma
      of nearly all subtypes, in addition to benign fibrofolliculomas, and pulmonary
      and renal cysts. BHD is caused by loss-of-function mutations in the folliculin
      (FLCN) protein. The molecular function of FLCN is still largely unknown; opposite
      and conflicting evidence of the role of FLCN in mammalian target of rapamycin
      signalling/phosphorylated ribosomal protein S6 (p-S6) activation had recently
      been reported. RESULTS AND METHODS: Here, the expression pattern of murine Flcn
      was described, and it was observed that homozygous disruption of Flcn results in
      embryonic lethality early during development. Importantly, heterozygous animals
      manifest early preneoplastic kidney lesions, devoid of Flcn expression, that
      progress towards malignancy, including cystopapillary adenomas. A bona fide
      tumour suppressor activity of FLCN was confirmed by nude mouse xenograft assays
      of two human RCC cell lines with either diminished or re-expressed FLCN. It was
      observed that loss of FLCN expression leads to context-dependent effects on S6
      activation. Indeed, solid tumours and normal kidneys show decreased p-S6 upon
      diminished FLCN expression. Conversely, p-S6 is found to be elevated or absent in
      FLCN-negative renal cysts. CONCLUSION: In accordance with clinical data showing
      distinct renal malignancies arising in BHD patients, in this study FLCN is shown
      as a general tumour suppressor in the kidney.

PMID- 19843505
TI  - Disruption of ST5 is associated with mental retardation and multiple congenital
      anomalies.
AB  - BACKGROUND: The authors observed a patient with a cryptic subtelomeric de novo
      balanced translocation 46,XY.ish t(11;20)(p15.4;q13.2) presenting with severe
      mental retardation, muscular hypotonia, seizures, bilateral sensorineural hearing
      loss, submucous cleft palate, persistent ductus Botalli, unilateral cystic kidney
      dysplasia and frequent infections. METHODS AND RESULTS: Fluorescence in situ
      hybridisation mapping and sequencing of the translocation breakpoints showed that
      no known genes are disrupted at 20q13.2 and that ST5 (suppression of
      tumorigenicity 5; MIM 140750) is disrupted on 11p15.4. By quantitative PCR from
      different human tissues, the authors found ST5 to be relatively evenly expressed
      in fetal tissues. ST5 expression was more pronounced in adult brain, kidney and
      muscle than in the corresponding fetal tissues, whereas expression in other
      tissues was generally lower than in the fetal tissue. Using RNA in situ
      hybridisation in mouse, the authors found that St5 is expressed in the frontal
      cortex during embryonic development. In adult mouse brain, expression of St5 was
      especially high in the hippocampal area and cerebellum. CONCLUSION: Hence, the
      authors suppose that ST5 plays an important role in central nervous system
      development probably due to disturbance of DENN-domain-mediated vesicle formation
      and neurotransmitter trafficking. Thus, these findings implicate ST5 in the
      aetiology of mental retardation, seizures and multiple congenital anomalies.

PMID- 19843506
TI  - Clinical trials: the viewpoint of children with a chronic illness compared with
      healthy children.
AB  - The views of over 200 children (11-16 years old, who were either healthy or
      attending paediatric medical clinics with a chronic illness) on issues relating
      to paediatric clinical trials were determined by a questionnaire. Children with a
      chronic illness had a better understanding of the concept of dosing of medicines
      (40% vs 23%) and placebo (34% vs 20%). They were more likely to support
      children's involvement in clinical trials (51% vs 37%). The altruistic nature of
      children in both groups was similar. It was of concern, however, that 57-63%
      children would participate as healthy volunteers in a cancer drug trial. Both
      groups were able to differentiate between the different types of illnesses where
      it is appropriate to study medicines in children (86-89% for illness where there
      is no treatment; 34-40% for 'me-too' drugs). Young people should be given more
      opportunities to be involved in decision-making regarding clinical trials of
      medicines.

PMID- 19843507
TI  - When should we be conducting thyroid function tests in newborns and young
      infants?
AB  - An audit of local practice was undertaken as regards requests for thyroid
      function tests (TFT) in children aged between birth and 3 months at two local
      hospitals in South West England between 2005 and 2008. A total of 406 tests were
      performed (2.6 tests per week) over a 2-year period at a teaching hospital (70
      tests per 1000 live births yearly), with 233 tests (1.5 tests per week) performed
      over a 3-year period at a local district hospital (39 tests per 1000 live births
      yearly). The highest proportion of all the tests was performed as routine
      investigation of prolonged neonatal jaundice (64% and 55%, respectively). Other
      common indications were maternal thyroid disorders (5.4% vs 4.7%) and suspected
      neonatal thyroid disorders (3% vs 9%). There was no confirmed diagnosis of
      infantile thyroid disease. Available evidence and this audit suggest that too
      many thyroid function tests are unnecessarily performed in young infants.

PMID- 19843508
TI  - Active smoking and second-hand-smoke exposure at home among Irish children, 1995
      2007.
AB  - OBJECTIVE: This study hypothesised a continual decline in current smoking
      prevalence over four calendar years (1995, 1998, 2002/03 and 2007) and no
      significant increase in second-hand-smoke (SHS) exposure levels at home after the
      workplace smoking ban of March 2004 (2007 versus 2002/03 survey) among Irish
      school children. METHODS: A modified ISAAC (International Study of Asthma and
      Allergies in Childhood) protocol was used. Children aged 13-14 years from
      randomly selected representative post-primary schools were studied: 2670 in 1995,
      2273 in 1998, 2892 in 2002-2003, and 2805 in 2007. ISAAC is a cross-sectional
      self-administered questionnaire survey. Smoking history was self-reported. beta
      Coefficients (slopes) of smoking rates across the four surveys were computed.
      Odds ratios for smoking rates were also computed using the baseline year (1995)
      as the reference period. All analyses were performed using SAS software (v 9.1).
      RESULTS: There were significant reductions in active smoking rates between 1995
      and 2007 (from 19.9% to 10.6%, respectively) resulting in 3.3% survey-to-survey
      reductions, with a significantly greater survey-to-survey decline among girls
      compared to boys (3.8% vs 2.7%, respectively). 45% of children were exposed to
      SHS at home in 2007. There was a statistically non-significant 2% overall decline
      in SHS exposure levels at home in 2007 relative to 2002/03, which was more
      pronounced in girls. CONCLUSIONS: The continual reduction in active smoking
      prevalence in children is welcome. That there was no significant increase in SHS
      exposure at home after the nationwide workplace smoking ban suggests that the ban
      did not increase smoking inside homes.

PMID- 19843509
TI  - Phenotypes of chronic fatigue syndrome in children and young people.
AB  - OBJECTIVE: To investigate the heterogeneity of chronic fatigue syndrome (CFS/ME)
      in children and young people. SETTING: Regional specialist CFS/ME service
      Patients Children and young people aged <19 years old. METHODS: Exploratory
      factor analysis was performed on symptoms present at assessment in 333 children
      and young people with CFS/ME. Linear and logistic regression analysis of data
      from self-completed assessment forms was used to explore the associations between
      the retained factors and sex, age, length of illness, depression, anxiety and
      markers of severity (fatigue, physical function, pain and school attendance).
      RESULTS: Three phenotypes were identified using factor analysis: muscoloskeletal
      (factor 1) had loadings on muscle and joint pain and hypersensitivity to touch,
      and was associated with worse fatigue (regression coefficient 0.47, 95% CI 0.25
      to 0.68, p<0.001), physical function (regression coefficient -0.52, 95% CI -0.83
      to -0.22, p=0.001) and pain. Factor 2 (migraine) loaded on noise and light
      hypersensitivity, headaches, nausea, abdominal pain and dizziness and was most
      strongly associated with physical function and pain. Sore throat phenotype
      (factor 3) had loadings on sore throat and tender lymph nodes and was not
      associated with fatigue or pain. There was no evidence that phenotypes were
      associated with age, length of illness or symptoms of depression (regression
      coefficient for association of depression with musculoskeletal pain -0.02, 95% CI
      -0.27 to 0.23, p=0.87). The migraine phenotype was associated with anxiety (0.40,
      95% CI 0.06 to 0.74, p=0.02). IMPLICATIONS: CFS/ME is heterogeneous in children
      with three phenotypes at presentation that are differentially associated with
      severity and are unlikely to be due to age or length of illness.

PMID- 19843510
TI  - Paediatric organ donation in the UK.

PMID- 19843511
TI  - Beta2 integrins modulate the initiation and progression of atherosclerosis in low
      density lipoprotein receptor knockout mice.
AB  - AIMS: Beta2 integrin-mediated adhesion is thought to be a key event in
      cardiovascular disease. However, results of clinical trials targeting these
      molecules have been disappointing. Here, we investigated the effect of
      inactivation of beta2 integrins at different stages of atherosclerosis by timed
      bone marrow transplantation (BMT) of CD18(-/-) cells in low-density lipoprotein
      receptor knockout (LDLR(-/-)) mice. METHODS AND RESULTS: Early BMT before fatty
      streak formation revealed a short-term protective effect of CD18 (34%
      atherosclerotic lesion reduction). Once fatty streak lesions had developed (5
      week atherogenic diet) before BMT, beta2 integrin expression did not affect
      lesion progression. However, after the establishment of more mature lesions (pre
      feeding mice the atherogenic diet for 10 weeks), CD18(+/+) BMT enhanced
      atherosclerosis (36%) lesion progression compared with CD18(-/-) BMT.
      Furthermore, beta2 integrins modulated the capacity of isolated peritoneal
      macrophages to take up acetylated LDL and native LDL and to phagocytose apoptotic
      cells, possibly via CD18-dependent mitogen-activated protein kinase signalling.
      Gene expression profile of CD18(-/-) and CD18(+/+) macrophages revealed
      significant differences in putative protective as well as atherogenic functions.
      CONCLUSION: beta2 integrin-mediated interaction between leucocytes and the vessel
      wall is a time-dependent and dynamic process. During the initiation phase, it
      protects against atherosclerotic lesion formation. However, with the evolution of
      the lesion and chronic exposure to dyslipidaemia, beta2 integrins' pro
      atherogenic action becomes dominant, accelerating the atherosclerotic process.

PMID- 19843512
TI  - Complete loss of murine Xin results in a mild cardiac phenotype with altered
      distribution of intercalated discs.
AB  - AIMS: Xin is a striated muscle-specific F-actin binding protein that has been
      implicated in cardiomyopathies. In cardiomyocytes, Xin is localized at
      intercalated discs (IDs). Mice lacking only two of the three Xin isoforms (XinAB(
      /-) mice) develop severe cardiac hypertrophy. To further investigate the function
      of Xin variants in the mammalian heart, we generated XinABC(-/-) mice deficient
      in all Xin isoforms. METHODS AND RESULTS: XinABC(-/-) mice showed a very mild
      phenotype: heart weight, heart weight to tibia length ratios, and cardiac
      dimensions were not altered. Increased perivascular fibrosis was only observed in
      hearts of young XinABC(-/-) mice. Striking differences were revealed in isolated
      cardiomyocytes: XinABC(-/-) cells demonstrated a significantly increased number
      of non-terminally localized ID-like structures. Furthermore, resting sarcomere
      length was increased, sarcomere shortening, peak shortening at 0.5-1 Hz, and the
      duration of shortening were decreased, and shortening and relengthening
      velocities were accelerated at frequencies above 4 Hz in XinABC(-/-)
      cardiomyocytes. ECG showed a significantly shorter HV interval and a trend
      towards shorter QRS interval in XinABC(-/-) mice, suggesting a faster conduction
      velocity of the ventricular-specific conduction system. In human cardiac tissue,
      expression of XinC protein was detected solely in samples from patients with
      cardiac hypertrophy. CONCLUSION: Total Xin deficiency leads to topographical ID
      alterations, premature fibrosis and subtle changes in contractile behaviour; this
      is a milder cardiac phenotype than that observed in XinAB(-/-) mice, which still
      can express XinC. Together with the finding that XinC is detected solely in
      cardiomyopathic human tissues, this suggests that its expression is responsible
      for the stronger dominant phenotype in XinAB(-/-) mice. Furthermore, it indicates
      that XinC may be involved in the development of human cardiac hypertrophy.

PMID- 19843513
TI  - Intrarenal artery superoxide is mainly NADPH oxidase-derived and modulates
      endothelium-dependent dilation in elderly patients.
AB  - AIMS: The present study was performed to investigate the contribution of NADPH
      oxidases (Nox) to superoxide formation in human renal proximal resistance
      arteries and to test whether superoxide formation contributes to acute
      vasoconstrictor responses and endothelium-dependent vasodilation in these
      vessels. METHODS AND RESULTS: Arcuate and proximal interlobular artery segments
      were from patients who underwent nephrectomy because of a renal tumour. Vessels
      were dissected from tumour-free parts of the kidneys. Additional intrarenal
      arteries were obtained from rats. Superoxide formation was measured by lucigenin
      enhanced chemiluminescence, expression of Nox isoforms was analysed by RT-PCR,
      and functional studies were performed by small vessel wire myography. Sixty per
      cent of superoxide formation in human arcuate and proximal interlobular arteries
      was due to Nox activity. mRNA expression analyses revealed the presence of Nox2
      and Nox4 but not Nox1. Phenylephrine and endothelin-1 induced powerful
      concentration-dependent vasoconstrictions that were unaffected by superoxide
      scavengers. Vasopressin elicited small and variable vasoconstrictions with signs
      of tachyphylaxis. Endothelium-dependent vasodilation was blunted by tiron and
      Nomega-nitro-L-arginine methyl ester but not by superoxide dismutase or catalase.
      Exogenous hydrogen peroxide elicited vasoconstriction. CONCLUSION: Nox activity
      is the major source of superoxide formation in renal proximal resistance arteries
      from elderly patients. Acute vasoconstrictor responses to alpha1-adrenoreceptor
      activation and to endothelin-1 do not depend on superoxide formation, while
      endothelium-dependent vasodilation in intrarenal arteries is reactive oxygen
      species-dependent.

PMID- 19843514
TI  - Proteomic remodelling of mitochondrial oxidative pathways in pressure overload
      induced heart failure.
AB  - AIMS: Impairment in mitochondrial energetics is a common observation in animal
      models of heart failure, the underlying mechanisms of which remain incompletely
      understood. It was our objective to investigate whether changes in mitochondrial
      protein levels may explain impairment in mitochondrial oxidative capacity in
      pressure overload-induced heart failure. METHODS AND RESULTS: Twenty weeks
      following aortic constriction, Sprague-Dawley rats developed contractile
      dysfunction with clinical signs of heart failure. Comparative mitochondrial
      proteomics using label-free proteome expression analysis (LC-MS/MS) revealed
      decreased mitochondrial abundance of fatty acid oxidation proteins (six of 11
      proteins detected), increased levels of pyruvate dehydrogenase subunits, and
      upregulation of two tricarboxylic acid cycle proteins. Regulation of
      mitochondrial electron transport chain subunits was variable, with downregulation
      of 53% of proteins and upregulation of 25% of proteins. Mitochondrial state 3
      respiration was markedly decreased independent of the substrate used (palmitoyl
      carnitine -65%, pyruvate -75%, glutamate -75%, dinitrophenol -82%; all P < 0.05),
      associated with impaired mitochondrial cristae morphology in failing hearts.
      Perfusion of isolated working failing hearts showed markedly reduced oleate (
      68%; P < 0.05) and glucose oxidation (-64%; P < 0.05). CONCLUSION: Pressure
      overload-induced heart failure is characterized by a substantial defect in
      cardiac oxidative capacity, at least in part due to a mitochondrial defect
      downstream of substrate-specific pathways. Numerous changes in mitochondrial
      protein levels have been detected, and the contribution of these to oxidative
      defects and impaired cardiac energetics in failing hearts is discussed.

PMID- 19843515
TI  - Activation of AMP-activated protein kinase suppresses oxidized low-density
      lipoprotein-induced macrophage proliferation.
AB  - Macrophage-derived foam cells play important roles in the progression of
      atherosclerosis. We reported previously that ERK1/2-dependent
      granulocyte/macrophage colony-stimulating factor (GM-CSF) expression, leading to
      p38 MAPK/ Akt signaling, is important for oxidized low density lipoprotein (Ox
      LDL)-induced macrophage proliferation. Here, we investigated whether activation
      of AMP-activated protein kinase (AMPK) could suppress macrophage proliferation.
      Ox-LDL-induced proliferation of mouse peritoneal macrophages was assessed by
      [(3)H]thymidine incorporation and cell counting assays. The proliferation was
      significantly inhibited by the AMPK activator 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR) and restored by dominant-negative AMPKalpha1, suggesting
      that AMPK activation suppressed macrophage proliferation. AICAR partially
      suppressed Ox-LDL-induced ERK1/2 phosphorylation and GM-CSF expression,
      suggesting that another mechanism is also involved in the AICAR-mediated
      suppression of macrophage proliferation. AICAR suppressed GM-CSF-induced
      macrophage proliferation without suppressing p38 MAPK/Akt signaling. GM-CSF
      suppressed p53 phosphorylation and expression and induced Rb phosphorylation.
      Overexpression of p53 or p27(kip) suppressed GM-CSF-induced macrophage
      proliferation. AICAR induced cell cycle arrest, increased p53 phosphorylation and
      expression, and suppressed GM-CSF-induced Rb phosphorylation via AMPK activation.
      Moreover, AICAR induced p21(cip) and p27(kip) expression via AMPK activation, and
      small interfering RNA (siRNA) of p21(cip) and p27(kip) restored AICAR-mediated
      suppression of macrophage proliferation. In conclusion, AMPK activation
      suppressed Ox-LDL-induced macrophage proliferation by suppressing GM-CSF
      expression and inducing cell cycle arrest. These effects of AMPK activation may
      represent therapeutic targets for atherosclerosis.

PMID- 19843516
TI  - Triadin deletion induces impaired skeletal muscle function.
AB  - Triadin is a multiple proteins family, some isoforms being involved in muscle
      excitation-contraction coupling, and some having still unknown functions. To
      obtain clues on triadin functions, we engineered a triadin knock-out mouse line
      and characterized the physiological effect of triadin ablation on skeletal muscle
      function. These mice presented a reduced muscle strength, which seemed not to
      alter their survival and has been characterized in the present work. We first
      checked in these mice the expression level of the different proteins involved in
      calcium homeostasis and observed in fast muscles an increase in expression of
      dihydropyridine receptor, with a large reduction in calsequestrin expression.
      Electron microscopy analysis of KO muscles morphology demonstrated the presence
      of triads in abnormal orientation and a reduction in the sarcoplasmic reticulum
      terminal cisternae volume. Using calcium imaging on cultured myotubes, we
      observed a reduction in the total amount of calcium stored in the sarcoplasmic
      reticulum. Physiological studies have been performed to evaluate the influence of
      triadin deletion on skeletal muscle function. Muscle strength has been measured
      both on the whole animal model, using hang test or electrical stimulation
      combined with NMR analysis and strength measurement, or on isolated muscle using
      electrical stimulation. All the results obtained demonstrate an important
      reduction in muscle strength, indicating that triadin plays an essential role in
      skeletal muscle function and in skeletal muscle structure. These results indicate
      that triadin alteration leads to the development of a myopathy, which could be
      studied using this new animal model.

PMID- 19843517
TI  - Role of microtubules in stress granule assembly: microtubule dynamical
      instability favors the formation of micrometric stress granules in cells.
AB  - Following exposure to various stresses (arsenite, UV, hyperthermia, and hypoxia),
      mRNAs are assembled into large cytoplasmic bodies known as "stress granules," in
      which mRNAs and associated proteins may be processed by specific enzymes for
      different purposes like transient storing, sorting, silencing, or other still
      unknown processes. To limit mRNA damage during stress, the assembly of
      micrometric granules has to be rapid, and, indeed, it takes only approximately 10
      20 min in living cells. However, such a rapid assembly breaks the rules of
      hindered diffusion in the cytoplasm, which states that large cytoplasmic bodies
      are almost immobile. In the present work, using HeLa cells and YB-1 protein as a
      stress granule marker, we studied three hypotheses to understand how cells
      overcome the limitation of hindered diffusion: shuttling of small messenger
      ribonucleoprotein particles from small to large stress granules, sliding of
      messenger ribonucleoprotein particles along microtubules, microtubule-mediated
      stirring of large stress granules. Our data favor the two last hypotheses and
      underline that microtubule dynamic instability favors the formation of
      micrometric stress granules.

PMID- 19843518
TI  - Structure and function of the intracellular region of the plexin-b1 transmembrane
      receptor.
AB  - Members of the plexin family are unique transmembrane receptors in that they
      interact directly with Rho family small GTPases; moreover, they contain a GTPase
      activating protein (GAP) domain for R-Ras, which is crucial for plexin-mediated
      regulation of cell motility. However, the functional role and structural basis of
      the interactions between the different intracellular domains of plexins remained
      unclear. Here we present the 2.4 A crystal structure of the complete
      intracellular region of human plexin-B1. The structure is monomeric and reveals
      that the GAP domain is folded into one structure from two segments, separated by
      the Rho GTPase binding domain (RBD). The RBD is not dimerized, as observed
      previously. Instead, binding of a conserved loop region appears to compete with
      dimerization and anchors the RBD to the GAP domain. Cell-based assays on mutant
      proteins confirm the functional importance of this coupling loop. Molecular
      modeling based on structural homology to p120(GAP).H-Ras suggests that Ras
      GTPases can bind to the plexin GAP region. Experimentally, we show that the
      monomeric intracellular plexin-B1 binds R-Ras but not H-Ras. These findings
      suggest that the monomeric form of the intracellular region is primed for GAP
      activity and extend a model for plexin activation.

PMID- 19843519
TI  - Histone deacetylase-1 is enriched at the platelet-derived growth factor-D
      promoter in response to interleukin-1beta and forms a cytokine-inducible gene
      silencing complex with NF-kappab p65 and interferon regulatory factor-1.
AB  - Understanding the mechanisms governing cytokine control of growth factor
      expression in smooth muscle cells would provide invaluable insight into the
      molecular regulation of vascular phenotypes and create future opportunities for
      therapeutic intervention. Here, we report that the proinflammatory cytokine
      interleukin (IL)-1beta suppresses platelet-derived growth factor (PDGF)-D
      promoter activity and mRNA and protein expression in smooth muscle cells. NF
      kappaB p65, induced by IL-1beta, interacts with a novel element in the PDGF-D
      promoter and inhibits PDGF-D transcription. Interferon regulatory factor-1 (IRF
      1) is also induced by IL-1beta and binds to a different element upstream in the
      promoter. Immunoprecipitation and chromatin immunoprecipitation experiments
      showed that IL-1beta stimulates p65 interaction with IRF-1 and the accumulation
      of both factors at the PDGF-D promoter. Mutation of the IRF-1 and p65 DNA-binding
      elements relieved the promoter from IL-1beta-mediated repression. PDGF-D
      repression by IL-1beta involves histone deacetylation and interaction of HDAC-1
      with IRF-1 and p65. HDAC-1 small interfering RNA ablates complex formation with
      IRF-1 and p65 and abrogates IRF-1 and p65 occupancy of the PDGF-D promoter. Thus,
      HDAC-1 is enriched at the PDGF-D promoter in cells exposed to IL-1beta and forms
      a cytokine-inducible gene-silencing complex with p65 and IRF-1.

PMID- 19843520
TI  - Beta integrin tyrosine phosphorylation is a conserved mechanism for regulating
      talin-induced integrin activation.
AB  - Integrins are large membrane-spanning receptors fundamental to cell adhesion and
      migration. Integrin adhesiveness for the extracellular matrix is activated by the
      cytoskeletal protein talin via direct binding of its phosphotyrosine-binding-like
      F3 domain to the cytoplasmic tail of the beta integrin subunit. The
      phosphotyrosine-binding domain of the signaling protein Dok1, on the other hand,
      has an inactivating effect on integrins, a phenomenon that is modulated by
      integrin tyrosine phosphorylation. Using full-length tyrosine-phosphorylated
      (15)N-labeled beta3, beta1A, and beta7 integrin tails and an NMR-based protein
      protein interaction assay, we show that talin1 binds to the NPXY motif and the
      membrane-proximal portion of beta3, beta1A, and beta7 tails, and that the
      affinity of this interaction is decreased by integrin tyrosine phosphorylation.
      Dok1 only interacts weakly with unphosphorylated tails, but its affinity is
      greatly increased by integrin tyrosine phosphorylation. The Dok1 interaction
      remains restricted to the integrin NPXY region, thus phosphorylation inhibits
      integrin activation by increasing the affinity of beta integrin tails for a talin
      competitor that does not form activating membrane-proximal interactions with the
      integrin. Key residues governing these specificities were identified by detailed
      structural analysis, and talin1 was engineered to bind preferentially to
      phosphorylated integrins by introducing the mutation D372R. As predicted, this
      mutation affects talin1 localization in live cells in an integrin phosphorylation
      specific manner. Together, these results indicate that tyrosine phosphorylation
      is a common mechanism for regulating integrin activation, despite subtle
      differences in how these integrins interact with their binding proteins.

PMID- 19843521
TI  - IRS1 regulation by Wnt/beta-catenin signaling and varied contribution of IRS1 to
      the neoplastic phenotype.
AB  - Dysregulation of beta-catenin levels and localization and constitutive activation
      of beta-catenin/TCF (T cell factor)-regulated gene expression occur in many
      cancers, including the majority of colorectal carcinomas and a subset of ovarian
      endometrioid adenocarcinomas. Based on the results of microarray-based gene
      expression profiling we found the insulin receptor substrate 1 (IRS1) gene as one
      of the most highly up-regulated genes upon ectopic expression of a mutant,
      constitutively active form of beta-catenin in the rat kidney epithelial cell line
      RK3E. We demonstrate expression of IRS1 can be directly activated by beta
      catenin, likely in part via beta-catenin/TCF binding to TCF consensus binding
      elements located in the first intron and downstream of the IRS1 transcriptional
      start site. Consistent with the proposal that beta-catenin is an important
      regulator of IRS1 expression in vivo, we observed that IRS1 is highly expressed
      in many cancers with constitutive stabilization of beta-catenin, such as
      colorectal carcinomas and ovarian endometrioid adenocarcinomas. Using a short
      hairpin RNA approach to abrogate IRS1 expression and function, we found that IRS1
      function is required for efficient de novo neoplastic transformation by beta
      catenin in RK3E cells. Our findings add to the growing body of data implicating
      IRS1 as a critical signaling component in cancer development and progression.

PMID- 19843522
TI  - Live cell analysis of aquaporin-4 m1/m23 interactions and regulated orthogonal
      array assembly in glial cells.
AB  - Aquaporin-4 (AQP4) can assemble into supramolecular aggregates called orthogonal
      arrays of particles (OAPs). In cells expressing single AQP4 isoforms, we found
      previously that OAP formation by AQP4-M23 requires N terminus interactions just
      downstream of Met-23 and that the inability of AQP4-M1 to form OAPs involves
      blocking by residues upstream of Met-23. Here, we studied M1/M23 interactions and
      regulated OAP assembly by nanometer-resolution tracking of quantum dot-labeled
      AQP4 in live cells expressing differentially tagged AQP4 isoforms and in primary
      glial cell cultures in which native AQP4 was labeled with a monoclonal
      recombinant neuromyelitis optica autoantibody. OAP assembly was assessed
      independently by Blue Native gel electrophoresis. We found that OAPs in native
      glial cells could be reproduced in transfected cells expressing equal amounts of
      AQP4-M1 and -M23. Mutants of M23 that do not themselves form OAPs, including M23
      F26Q and M23-G28P, were able to fully co-associate with native M23 to form large
      immobile OAPs. Analysis of a palmitoylation-null M1 mutant (C13A/C17A) indicated
      palmitoylation-dependent OAP assembly only in the presence of M23, with increased
      M1 palmitoylation causing progressive OAP disruption. Differential regulation of
      OAP assembly by palmitoylation, calcium elevation, and protein kinase C
      activation was found in primary glial cell cultures. We conclude that M1 and M23
      co-assemble in AQP4 OAPs and that specific signaling events can regulate OAP
      assembly in glial cells.

PMID- 19843523
TI  - Determination of a chloroplast degron in the regulatory domain of chlorophyllide
      a oxygenase.
AB  - Chlorophyll b is one of the major photosynthetic pigments of plants. The
      regulation of chlorophyll b biosynthesis is important for plants in order to
      acclimate to changing environmental conditions. In the chloroplast, chlorophyll b
      is synthesized from chlorophyll a by chlorophyllide a oxygenase (CAO), a Rieske
      type monooxygenase. The activity of this enzyme is regulated at the level of
      protein stability via a feedback mechanism through chlorophyll b. The Clp
      protease and the N-terminal domain (designated the A domain) of CAO are essential
      for the regulatory mechanism. In this study, we aimed to identify the specific
      amino acid residue or the sequence within the A domain that is essential for this
      regulation. To accomplish this goal, we randomly introduced base substitutions
      into the A domain and searched for potentially important residues by analyzing
      1,000 transformants of Arabidopsis thaliana. However, none of the single amino
      acid substitutions significantly stabilized CAO. Therefore, we generated serial
      deletions in the A domain and expressed these deletions in the background of CAO
      deficient Arabidopsis mutant. We found that the amino acid sequence
      (97)QDLLTIMILH(106) is essential for the regulation of the protein stability. We
      furthermore determined that this sequence induces the destabilization of green
      fluorescent protein. These results suggest that this sequence serves as a
      degradation signal that is recognized by proteases functioning in the
      chloroplast.

PMID- 19843524
TI  - The 19 s proteasome subcomplex establishes a specific protein interaction network
      at the promoter for stimulated transcriptional initiation in vivo.
AB  - The 26 S proteasome complex that comprises the 20 S core and 19 S regulatory
      (with six ATPases) particles is engaged in an ATP-dependent degradation of a
      variety of key regulatory proteins and, thus, controls important cellular
      processes. Interestingly, several recent studies have implicated the 19 S
      regulatory particle in controlling eukaryotic transcriptional initiation or
      activation independently of the 20 S core particle. However, the mechanism of
      action of the 19 S proteasome subcomplex in regulation of eukaryotic
      transcriptional activation is not clearly understood in vivo. Here, using a
      chromatin immunoprecipitation assay in conjunction with mutational and
      transcriptional analyses in Saccharomyces cerevisiae, we show that the 19 S
      proteasomal subcomplex establishes a specific protein interaction network at the
      upstream activating sequence of the promoter. Such an interaction network is
      essential for formation of the preinitiation complex at the core promoter to
      initiate transcription. Furthermore, we demonstrate that the formation of the
      transcription complex assembly at the promoter is dependent on 19 S ATPase
      activity. Intriguingly, 19 S ATPases appear to cross-talk for stimulation of the
      assembly of transcription factors at the promoter. Together, these results
      provide significant insights as to how the 19 S proteasome subcomplex regulates
      the formation of the active transcription complex assembly (and, hence,
      transcriptional initiation) at the promoter in vivo.

PMID- 19843525
TI  - Vesicular inhibitory amino acid transporter is a Cl-/gamma-aminobutyrate Co
      transporter.
AB  - The vesicular inhibitory amino acid transporter (VIAAT) is a synaptic vesicle
      protein responsible for the vesicular storage of gamma-aminobutyrate (GABA) and
      glycine which plays an essential role in GABAergic and glycinergic
      neurotransmission. The transport mechanism of VIAAT remains largely unknown.
      Here, we show that proteoliposomes containing purified VIAAT actively took up
      GABA upon formation of membrane potential (Deltapsi) (positive inside) but not
      DeltapH. VIAAT-mediated GABA uptake had an absolute requirement for Cl(-) and
      actually accompanied Cl(-) movement. Kinetic analysis indicated that one GABA
      molecule and two Cl(-) equivalents were transported during one transport cycle.
      VIAAT in which Glu(213) was specifically mutated to alanine completely lost the
      ability to take up both GABA and Cl(-). Essentially the same results were
      obtained with glycine, another substrate of VIAAT. These results demonstrated
      that VIAAT is a vesicular Cl(-) transporter that co-transports Cl(-) with GABA or
      glycine in a Deltapsi dependent manner. It is concluded that Cl(-) plays an
      essential role in vesicular storage of GABA and glycine.

PMID- 19843526
TI  - MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4)
      transcription in pancreatic islet beta cells.
AB  - Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor,
      serves as a master regulator in the pancreas because of its importance during
      organogenesis and in adult islet insulin-producing beta cell activity. Here, we
      show that KLF11, an SP/Kruppel-like (SP/KLF) transcription factor, mutated in
      French maturity onset diabetes of the young patients (MODY7), regulates Pdx-1
      transcription in beta cells through two evolutionarily conserved GC-rich motifs
      in conserved Area II, a control region essential to islet beta cell-enriched
      expression. These regulatory elements, termed GC1 (human base pair -2061/-2055)
      and GC2 (-2036/-2027), are also nearly identical to the consensus KLF11 binding
      sequence defined here by random oligonucleotide binding analysis. KLF11
      specifically associates with Area II in chromatin immunoprecipitation assays,
      while preventing binding to GC1- and/or GC2-compromised Pdx1-driven reporter
      activity in beta cell lines. Mechanistically, we find that KLF11 interacts with
      the coactivator p300 via its zinc finger domain in vivo to mediate Pdx-1
      activation. Together, our data identified a hierarchical regulatory cascade for
      these two MODY genes, suggesting that gene regulation in MODY is more complex
      than anticipated previously. Furthermore, because KLF11 like most MODY-associated
      transcription factors uses p300, these data further support a role for this
      coactivator as a critical chromatin link in forms of type 2 diabetes.

PMID- 19843527
TI  - Biochemical control of CARM1 enzymatic activity by phosphorylation.
AB  - Coactivator-associated arginine methyltransferase 1 (CARM1) is a dual functional
      coregulator that facilitates transcription initiation by methylation of Arg(17)
      and Arg(26) of histone H3 and also dictates the subsequent coactivator complex
      disassembly by methylation of the steroid receptor coactivator family
      coactivators and p300/cAMP-response element-binding protein-binding protein.
      However, the regulation of CARM1 enzymatic activity and substrate specificity
      remains largely unknown. In this study, we report that CARM1 function is
      regulated by phosphorylation at Ser(217), a residue completely conserved in the
      type I protein arginine methyltransferase (PRMT) family of enzymes. Comparative
      analysis of the published CARM1 crystal structures reveals that the hydroxyl
      group of Ser(217) forms a strong hydrogen bond with the carbonyl oxygen atom of
      Tyr(154) to lock the cofactor S-adenosylmethionine inside the binding cavity.
      Phosphorylation of Ser(217) disrupts this hydrogen bond and subsequently
      abolishes S-adenosylmethionine binding and its methyltransferase activity.
      Importantly, Tyr(154) is also conserved in the type I PRMT family of enzymes,
      suggesting a general role of this hydrogen bond in maintaining the holo structure
      of the type I PRMT catalytic domain. Moreover, we found that phosphorylation at
      Ser(217) also promoted CARM1 cytoplasmic localization and that this translocation
      occurred mainly during mitosis. We propose that phosphorylation at Ser(217)
      serves as a molecular switch for controlling CARM1 enzymatic activity during the
      cell cycle.

PMID- 19843528
TI  - Transcriptional activation of hTERT, the human telomerase reverse transcriptase,
      by nuclear factor of activated T cells.
AB  - Telomerase is essential for telomere maintenance, and its activation is thought
      to be a critical step in cellular immortalization and tumorigenesis. Human
      telomerase reverse transcriptase (hTERT) is a major component of telomerase
      activity. We show here that hTERT is expressed soon after lymphocyte activation
      and that its expression is inhibited by rapamycin, wortmannin, and FK506, which
      was the most potent inhibitor. These results suggest a potential role for the
      transcription factor nuclear factor of activated T cells (NFAT) in the regulation
      of hTERT expression. Five putative NFAT-binding sites were identified in the
      hTERT promoter. In luciferase assays, the hTERT promoter was activated by
      overexpressed NFAT1. Moreover, serial deletions revealed that the promoter
      activation was mainly due to a -40 NFAT1-binding site flanked by two SP1-binding
      sites. Mutation of the -40 NFAT-binding site caused a 53% reduction in the
      transcriptional activity of hTERT promoter. Simultaneous mutations of the -40
      NFAT-responsive element together with one or both SP1-binding sites led to a more
      dramatic decrease in luciferase activity than single mutations, suggesting a
      functional synergy between NFAT1 and SP1 in hTERT transcriptional regulation.
      NFAT1 overexpression in MCF7 and Jurkat cell lines induced an increase in
      endogenous hTERT mRNA expression. Inversely, its down-regulation was induced by
      NFAT1 silencing. Furthermore, chromatin immunoprecipitation assay demonstrated
      that NFAT1 directly binds to two sites (-40 and -775) in the endogenous hTERT
      promoter. Thus, we show for the first time the direct involvement of NFAT1 in the
      transcriptional regulation of hTERT.

PMID- 19843529
TI  - Yeast AEP3p is an accessory factor in initiation of mitochondrial translation.
AB  - Initiation of protein synthesis in mitochondria and chloroplasts normally uses a
      formylated initiator methionyl-tRNA (fMet-tRNA(f)(Met)). However, mitochondrial
      protein synthesis in Saccharomyces cerevisiae can initiate with nonformylated Met
      tRNA(f)(Met), as demonstrated in yeast mutants in which the nuclear gene encoding
      mitochondrial methionyl-tRNA formyltransferase (FMT1) has been deleted. The role
      of formylation of the initiator tRNA is not known, but in vitro formylation
      increases binding of Met-tRNA(f)(Met) to translation initiation factor 2 (IF2).
      We hypothesize the existence of an accessory factor that assists mitochondrial
      IF2 (mIF2) in utilizing unformylated Met-tRNA(f)(Met). This accessory factor
      might be unnecessary when formylated Met-tRNA(f)(Met) is present but becomes
      essential when only the unformylated species are available. Using a synthetic
      petite genetic screen in yeast, we identified a mutation in the AEP3 gene that
      caused a synthetic respiratory-defective phenotype together with Delta fmt1. The
      same aep3 mutation also caused a synthetic respiratory defect in cells lacking
      formylated Met-tRNA(f)(Met) due to loss of the MIS1 gene that encodes the
      mitochondrial C(1)-tetrahydrofolate synthase. The AEP3 gene encodes a peripheral
      mitochondrial inner membrane protein that stabilizes mitochondrially encoded
      ATP6/8 mRNA. Here we show that the AEP3 protein (Aep3p) physically interacts with
      yeast mIF2 both in vitro and in vivo and promotes the binding of unformylated
      initiator tRNA to yeast mIF2. We propose that Aep3p functions as an accessory
      initiation factor in mitochondrial protein synthesis.

PMID- 19843534
TI  - Sex workers can be screened too often: a cost-effectiveness analysis in Victoria,
      Australia.
AB  - OBJECTIVES: Commercial sex is licensed in Victoria, Australia such that sex
      workers are required to have regular tests for sexually transmitted infections
      (STIs). However, the incidence and prevalence of STIs in sex workers are very
      low, especially since there is almost universal condom use at work. We aimed to
      conduct a cost-effectiveness analysis of the financial cost of the testing policy
      versus the health benefits of averting the transmission of HIV, syphilis,
      chlamydia and gonorrhoea to clients. METHODS: We developed a simple mathematical
      transmission model, informed by conservative parameter estimates from all
      available data, linked to a cost-effectiveness analysis. RESULTS: We estimated
      that under current testing rates, it costs over $A90,000 in screening costs for
      every chlamydia infection averted (and $A600,000 in screening costs for each
      quality-adjusted life year (QALY) saved) and over $A4,000,000 for every HIV
      infection averted ($A10,000,000 in screening costs for each QALY saved). At an
      assumed willingness to pay of $A50,000 per QALY gained, HIV testing should not be
      conducted less than approximately every 40 weeks and chlamydia testing
      approximately once per year; in comparison, current requirements are testing
      every 12 weeks for HIV and every 4 weeks for chlamydia. CONCLUSIONS: Mandatory
      screening of female sex workers at current testing frequencies is not cost
      effective for the prevention of disease in their male clients. The current
      testing rate required of sex workers in Victoria is excessive. Screening
      intervals for sex workers should be based on local STI epidemiology and not
      locked by legislation.

PMID- 19843535
TI  - Neisseria gonorrhoeae multi-antigen sequence typing using non-cultured clinical
      specimens.
AB  - OBJECTIVES: The Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST)
      system, based on PCR amplification and sequence analysis of the gonococcal porB
      and tbpB genes, is widely used for molecular typing of gonococcal isolates but is
      not validated for non-cultured clinical samples. This study sought to examine the
      performance of the NG-MAST system on a range of non-cultured samples. METHODS:
      Nucleic acid extracts of 73 N gonorrhoeae-positive samples, comprising eight
      cervical swabs, nine urethral swabs, 35 urine samples, one vaginal swab, 13
      rectal swabs and seven throat swabs, were analysed by NG-MAST. For 27 specimens,
      corresponding gonococcal isolates were also analysed and the results compared. A
      panel of 44 non-gonococcal Neisseria strains and 100 N gonorrhoeae-negative
      clinical samples were used to investigate further the specificity of the NG-MAST
      PCR reactions. RESULTS: PCR amplification and DNA sequencing of gonococcal porB
      and tbpB genes was successful for all N gonorrhoeae-positive urogenital
      specimens, 11 of 13 rectal swabs and four of seven throat swabs. For the 27 N
      gonorrhoeae-positive specimens with corresponding gonococcal isolates, the porB
      and tbpB sequences obtained from the non-cultured specimen were identical to
      those obtained from the isolate. Cross-reaction with non-gonococcal Neisseria
      species was observed for both the porB and tbpB PCR reactions, and proved to be
      problematical for NG-MAST typing of throat swab specimens. CONCLUSIONS: The NG
      MAST system can successfully be applied directly to non-cultured urogenital
      samples, but is less suitable for extragenital specimens, particularly throat
      swabs, due to cross-reaction with commensal Neisseria species.

PMID- 19843536
TI  - The prevalence of urethral and rectal Mycoplasma genitalium and its associations
      in men who have sex with men attending a genitourinary medicine clinic.
AB  - OBJECTIVES: To determine the prevalence of rectal and urethral Mycoplasma
      genitalium (MG) in men who have sex with men (MSM) attending a genitourinary
      medicine clinic and to measure its associations with symptoms, clinical signs,
      sexual behaviour and concomitant sexually transmitted infections (STI). METHODS:
      MSM attending for STI screening were tested for MG using a real-time PCR assay
      that targets the MgPa gene. Data were collected on demographics, sexual
      behaviour, past STI history and clinical symptoms and signs. RESULTS: 849 first
      void urine and rectal specimens were collected from 438 MSM. The overall
      prevalence of MG in MSM was 6.6% with first-void urine positivity of 2.7% and
      rectal positivity of 4.4%. MG was significantly associated with HIV positivity
      (OR 7.6, 95% CI 3.2 to 18.7, p<0.001) in contrast to Chlamydia trachomatis (OR
      1.5, 95% CI 0.5 to 4.1, p=0.4) and Neisseria gonorrhoeae (OR 1.7, 95% CI 0.7 to
      3.8, p=0.194). MG was more prevalent than C trachomatis (p=0.15) and N
      gonorrhoeae (p=0.02) in this subgroup of HIV-positive MSM. Urethral infection was
      associated with dysuria (p<0.001) but there was no association between rectal
      infection and anorectal symptoms or signs. CONCLUSION: Rates of MG are much
      higher in HIV-positive MSM than HIV-negative MSM at both urethral and rectal
      sites, and MG is more prevalent in HIV-positive MSM than other bacterial STI.
      Although the subclinical nature of MG in the rectum questions its significance,
      the high prevalence seen at this site could be a potential source of onward
      urethral transmission. Future work should assess the need for appropriate
      screening and treatment of MG infection in MSM, particularly those with HIV
      infection and high-risk sexual behaviour.

PMID- 19843537
TI  - Time course of changes in ocular wavefront aberration after instillation of 0.5%
      timolol gel-forming solution.
AB  - AIMS: To investigate the influence of 0.5% timolol gel-forming solution on ocular
      wavefront aberrations. METHODS: In 17 normal volunteers, ocular aberration was
      assessed before and 5 min, 30 min, 1 h, 2 h, 3 h, 6 h and 12 h after instillation
      of timolol gel-forming solution. Ocular aberration was sequentially measured over
      a period of 10 s, and the root-mean-square (RMS) of the second-, third-, fourth-
      and total higher-order aberrations (HOAs) were determined. From the time course
      of changes in total HOAs in 10 s, the stability index (SI) and fluctuation index
      (FI) were calculated. The authors also investigated sequential changes in
      specific Zernike components such as vertical coma, horizontal coma and spherical
      aberration. RESULTS: No significant changes in second-order RMS were observed
      (p=0.452, repeated-measures ANOVA). Topical instillation significantly increased
      HOAs such as third-, fourth- and total higher-order RMS (p=0.023, p=0.007 and
      p=0.003, respectively). Multiple comparison analysis revealed significant
      increases in HOAs 5 min after instillation (p=0.005 for third-, p=0.001 for
      fourth- and p<0.001 for total higher-order RMS, Dunnett post hoc test). FI
      increased significantly 5 min after instillation (p=0.013), but SI did not change
      significantly. With respect to sequential changes in specific components,
      significant changes were observed in vertical coma (p=0.004, repeated-measures
      ANOVA) and horizontal coma (p=0.005), but not in spherical aberration.
      CONCLUSION: Instillation of timolol gel-forming solution significantly degrades
      optical quality of the eye for approximately 5 min by increasing HOAs, which may
      cause blurred vision.

PMID- 19843538
TI  - Endothelial progenitor cells: trick or treat?

PMID- 19843539
TI  - The homeobox gene CHX10/VSX2 regulates RdCVF promoter activity in the inner
      retina.
AB  - Rod-derived Cone Viability Factor (RdCVF) is a trophic factor with therapeutic
      potential for the treatment of retinitis pigmentosa, a retinal disease that
      commonly results in blindness. RdCVF is encoded by Nucleoredoxin-like 1 (Nxnl1),
      a gene homologous with the family of thioredoxins that participate in the defense
      against oxidative stress. RdCVF expression is lost after rod degeneration in the
      first phase of retinitis pigmentosa, and this loss has been implicated in the
      more clinically significant secondary cone degeneration that often occurs. Here,
      we describe a study of the Nxnl1 promoter using an approach that combines
      promoter and transcriptomic analysis. By transfection of selected candidate
      transcription factors, chosen based upon their expression pattern, we identified
      the homeodomain proteins CHX10/VSX2, VSX1 and PAX4, as well as the zinc finger
      protein SP3, as factors that can stimulate both the mouse and human Nxnl1
      promoter. In addition, CHX10/VSX2 binds to the Nxnl1 promoter in vivo. Since
      CHX10/VSX2 is expressed predominantly in the inner retina, this finding motivated
      us to demonstrate that RdCVF is expressed in the inner as well as the outer
      retina. Interestingly, the loss of rods in the rd1 mouse, a model of retinitis
      pigmentosa, is associated with decreased expression of RdCVF by inner retinal
      cells as well as by rods. Based upon these results, we propose an alternative
      therapeutic strategy aimed at recapitulating RdCVF expression in the inner
      retina, where cell loss is not significant, to prevent secondary cone death and
      central vision loss in patients suffering from retinitis pigmentosa.

PMID- 19843540
TI  - Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of
      primordial follicles.
AB  - To maintain the female reproductive lifespan, the majority of ovarian primordial
      follicles are preserved in a quiescent state in order to provide ova for later
      reproductive life. However, the molecular mechanism that maintains the long
      quiescence of primordial follicles is poorly understood. Here we provide genetic
      evidence to show that the tumor suppressor tuberous sclerosis complex 1 (Tsc1),
      which negatively regulates mammalian target of rapamycin complex 1 (mTORC1),
      functions in oocytes to maintain the quiescence of primordial follicles. In
      mutant mice lacking the Tsc1 gene in oocytes, the entire pool of primordial
      follicles is activated prematurely due to elevated mTORC1 activity in the oocyte,
      ending up with follicular depletion in early adulthood and causing premature
      ovarian failure (POF). We further show that maintenance of the quiescence of
      primordial follicles requires synergistic, collaborative functioning of both Tsc
      and PTEN (phosphatase and tensin homolog deleted on chromosome 10) and that these
      two molecules suppress follicular activation through distinct ways. Our results
      suggest that Tsc/mTORC1 signaling and PTEN/PI3K (phosphatidylinositol 3 kinase)
      signaling synergistically regulate the dormancy and activation of primordial
      follicles, and together ensure the proper length of female reproductive life.
      Deregulation of these signaling pathways in oocytes results in pathological
      conditions of the ovary, including POF and infertility.

PMID- 19843541
TI  - SUMOylation attenuates the aggregation propensity and cellular toxicity of the
      polyglutamine expanded ataxin-7.
AB  - Post-translational modification by SUMO (small ubiquitin-like modifier) was
      proposed to modulate the pathogenesis of several neurodegenerative diseases.
      Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder, whose
      pathology is caused by an expansion of a polyglutamine stretch in the protein
      ataxin-7 (ATXN7). Here, we identified ATXN7 as new target for SUMOylation in
      vitro and in vivo. The major SUMO acceptor site was mapped to lysine 257, which
      is part of an evolutionarily conserved consensus SUMOylation motif. SUMOylation
      did not influence the subcellular localization of ATXN7 nor its interaction with
      components of the TFTC/STAGA complex. Expansion of the polyglutamine stretch did
      not impair the SUMOylation of ATXN7. Furthermore, SUMO1 and SUMO2 colocalized
      with ATXN7 in a subset of neuronal intranuclear inclusions in the brain of SCA7
      patients and SCA7 knock-in mice. In a COS-7 cellular model of SCA7, in addition
      to diffuse nucleoplasmic staining we identified two populations of nuclear
      inclusions: homogenous or non-homogenous. Non-homogenous inclusions showed
      significantly reduced colocalization with SUMO1 and SUMO2, but were highly
      enriched in Hsp70, 19S proteasome and ubiquitin. Interestingly, they were
      characterized by increased staining with the apoptotic marker caspase-3 and by
      disruption of PML nuclear bodies. Importantly, preventing the SUMOylation of
      expanded ATXN7 by mutating the SUMO site increased both the amount of SDS
      insoluble aggregates and of caspase-3 positive non-homogenous inclusions, which
      act toxic to the cells. Our results demonstrate an influence of SUMOylation on
      the multistep aggregation process of ATXN7 and implicate a role for ATXN7
      SUMOylation in SCA7 pathogenesis.

PMID- 19843542
TI  - PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for
      an Nepsilon-dimethyl lysine demethylase.
AB  - Mutations of human PHF8 cluster within its JmjC encoding exons and are linked to
      mental retardation (MR) and a cleft lip/palate phenotype. Sequence comparisons,
      employing structural insights, suggest that PHF8 contains the double stranded
      beta-helix fold and ferrous iron binding residues that are present in 2
      oxoglutarate-dependent oxygenases. We report that recombinant PHF8 is an Fe(II)
      and 2-oxoglutarate-dependent N(epsilon)-methyl lysine demethylase, which acts on
      histone substrates. PHF8 is selective in vitro for N(epsilon)-di- and mono
      methylated lysine residues and does not accept trimethyl substrates. Clinically
      observed mutations to the PHF8 gene cluster in exons encoding for the double
      stranded beta-helix fold and will therefore disrupt catalytic activity. The PHF8
      missense mutation c.836C>T is associated with mild MR, mild dysmorphic features,
      and either unilateral or bilateral cleft lip and cleft palate in two male
      siblings. This mutant encodes a F279S variant of PHF8 that modifies a conserved
      hydrophobic region; assays with both peptides and intact histones reveal this
      variant to be catalytically inactive. The dependence of PHF8 activity on oxygen
      availability is interesting because the occurrence of fetal cleft lip has been
      demonstrated to increase with maternal hypoxia in mouse studies. Cleft lip and
      other congenital anomalies are also linked indirectly to maternal hypoxia in
      humans, including from maternal smoking and maternal anti-hypertensive treatment.
      Our results will enable further studies aimed at defining the molecular links
      between developmental changes in histone methylation status, congenital disorders
      and MR.

PMID- 19843544
TI  - Methods for spectral interference corrections for direct measurements of 234U and
      230Th in materials by gamma-ray spectrometry.
AB  - When the high-resolution gamma-ray spectrometry was used in the analysis of
      (234)U and (230)Th in samples, there is a much more need to correct for the
      measured activity results of (234)U and (230)Th mainly due to self-absorption
      effects and the interfering lines from (226)Ra, (235)U, (238)U and their decay
      products that often might be present in the samples. Therefore, in the present
      study, the methods for the spectral interference corrections for the analytical
      peaks of (234)U and (230)Th are suggested to take into account the contributions
      of the overlapping gamma rays to these peaks. For the method validation, direct
      gamma-ray spectrometric measurements were carried out using certified reference
      materials (CRM) by use of a 76.5 % n-type Ge detector. The activities measured
      for the CRM samples were corrected for spectral interferences, self-absorption
      and true coincidence-summing (TCS) effects. The obtained results indicate that
      ignoring of the contribution of the interference gamma rays to the main
      analytical peak at 53.2 keV of (234)U leads to a lager systematic error of 87.3
      90.4 % for the measured activities of (234)U, and similarly if one ignores the
      contributions of the interference gamma rays to the main analytical peak at 67.7
      keV of (230)Th, this leads to a much smaller systematic error of 2.1-2.7 % for
      the activities of (230)Th. Therefore, the required correction factors for
      spectral interferences to the analytical peaks of (234)U and (230)Th are not
      negligible and thus they should also be considered besides necessary self
      absorption factors to determine more accurate activities in the samples. On the
      other hand, it is estimated that although the TCS effects on the main analytical
      peaks of both (234)U and (230)Th are negligibly small, those TCS correction
      factors for their interference gamma rays to these peaks should be taken into
      account when direct measurements are performed in a close-counting geometry
      condition. Otherwise, the resulted activities can have serious erroneous results
      for both (234)U and (230)Th while using gamma-ray spectrometry, thereby leading
      to inaccuracies in their derived quantities, for instance, the corresponding age
      determinations of the samples.

PMID- 19843543
TI  - Proteotoxic stress increases nuclear localization of ataxin-3.
AB  - Spinocerebellar ataxia type 3 (SCA3)/Machado Joseph disease results from
      expansion of the polyglutamine domain in ataxin-3 (Atx3). Atx3 is a
      transcriptional co-repressor, as well as a deubiquitinating enzyme that appears
      to function in cellular pathways involved in protein homeostasis. In this study,
      we show that interactions of Atx3 with valosin-containing protein and hHR23B are
      dynamic and modulated by proteotoxic stresses. Heat shock, a general proteotoxic
      stress, also induced wild-type and pathogenic Atx3 to accumulate in the nucleus.
      Mapping studies showed that two regions of Atx3, the Josephin domain and the C
      terminus, regulated heat shock-induced nuclear localization. Heat shock-induced
      nuclear localization of Atx3 was not affected by a casein kinase-2 inhibitor or
      by mutating a predicted nuclear localization signal. However, serine-111 of Atx3
      was required for nuclear localization of the Josephin domain and regulated
      nuclear localization of full-length Atx3. Atx3 null cells were more sensitive to
      toxic effects of heat shock suggesting that Atx3 had a protective function in the
      cellular response to heat shock. Importantly, we found that oxidative stress also
      induced nuclear localization of Atx3; both wild-type and pathogenic Atx3
      accumulated in the nucleus of SCA3 patient fibroblasts following oxidative
      stress. Heat shock and oxidative stress are the first processes identified that
      increase nuclear localization of Atx3. Observations in this study provide new and
      important insights for understanding SCA3 pathology as the nucleus is likely a
      key site for early pathogenesis.

PMID- 19843545
TI  - Study of atmospheric aerosols and mixing layer by LIDAR.
AB  - The LIDAR (laser radar) is an active remote sensing technique, which allows for
      the altitude-resolved observation of several atmospheric constituents. A typical
      application is the measurement of the vertically resolved aerosol optical
      properties. By using aerosol particles as a marker, continuous determination of
      the mixing layer height (MLH) can also be obtained by LIDAR. Some examples of
      aerosol extinction coefficient profiles and MLH extracted from a 1-year LIDAR
      data set collected in Milan (Italy) are discussed and validated against in situ
      data (from a balloon-borne optical particle counter). Finally a comparison of the
      observation-based MLH with relevant numerical simulations (mesoscale model MM5)
      is provided.

PMID- 19843546
TI  - Urban exposure to ELF magnetic field due to high-, medium- and low-voltage
      electricity supply networks.
AB  - The regional environment protection agency (ARPA) of the Aosta Valley region in
      north Italy performed a survey of magnetic field triggered by the power supply
      network in high, medium and low voltages on the entire area of Aosta town. The
      electrical distribution system for houses was not however taken into account. The
      aim of the survey was to evaluate the global population exposure and not simply
      the assessment of the legal exposure limit compliance.

PMID- 19843547
TI  - Intercomparison of magnetic field measurements near MV/LV transformer
      substations: methodological planning and results.
AB  - Within the framework of Environmental Agencies system's activities, coordinated
      by ISPRA (superior institute for environmental protection and research), a
      comparison among measurements was designed and accomplished, in order to go into
      depth on the matter of measurement problems and to evaluate magnetic field at
      power frequencies. These measurements have been taken near medium voltage /low
      voltage transformer substation. This project was developed with the contribution
      of several experts who belong to different Regional Agencies. In three of these
      regions, substations having specific international standard characteristics were
      chosen; then a measurement and data analysis protocol was arranged. Data analysis
      showed a good level of coherence among results obtained by different
      laboratories. However, a range of problems emerged, either during the protocol
      predisposition and definition of the data analysis procedure or during the
      execution of measures and data reprocessing, because of the spatial and temporal
      variability of magnetic field. These problems represent elements of particular
      interest in determining a correct measurement methodology, whose purpose is the
      comparison with limits of exposure, attention values and quality targets.

PMID- 19843548
TI  - What is radiation protection dosimetry?

PMID- 19843550
TI  - Staging algorithm for diffuse malignant pleural mesothelioma.
AB  - An algorithm of preoperative mediastinal nodal staging with
      endobronchial/endoesophageal ultrasonography (EBUS/EUS) and transcervical
      extended mediastinal lymphadenectomy (TEMLA) combined with laparoscopy/peritoneal
      lavage and cytology was analyzed to establish the realistic criteria for radical
      multimodality treatment of malignant pleural mesothelioma (MPM). The algorithm
      included computed tomography (CT), thoracoscopy with multiple pleural biopsies
      and talc pleurodesis, EBUS/EUS and one-stage TEMLA and laparoscopy/peritoneal
      lavage and cytology of the fluid. Forty-two patients were diagnosed from 1
      January 2004 to 31 December 2008. There were 16 women and 26 men in ages ranging
      from 43 to 77 years (mean 57.8); 31 epithelioid, 2 sarcomatoid and 9 biphasic
      type MPM. 21/42 patients were considered possible candidates for multimodality
      treatment. Three patients who received neoadjuvant chemotherapy were excluded
      from this study. EBUS/EUS was performed to stage the mediastinal nodes. In 3/18
      patients metastatic nodes were discovered. In the rest of the 15 patients
      simultaneous TEMLA and laparoscopy/peritoneal lavage and cytology of the fluid
      were performed. In three patients TEMLA was positive, in six patients laparoscopy
      was positive and in two patients both TEMLA and laparoscopy were positive.
      Finally, 4/42 (9.5%) patients underwent thoracotomy with one exploration (chest
      wall infiltration) and three pleuropneumonectomies with the subsequent chemo- and
      radiotherapy. The proposed algorithm of preoperative staging spared the majority
      of MPM patients from futile surgery.

PMID- 19843549
TI  - MODIS and OMI satellite observations supporting air quality monitoring.
AB  - Within the framework of air quality monitoring, measurements by Earth-observing
      satellite sensors are combined here with regional meteorological and chemical
      transport models. Two satellite-derived products developed within the QUITSAT
      project, regarding significant pollutants including PM(2.5) and NO(2), are
      presented. Estimates of PM(2.5) concentrations at ground level were obtained
      using moderate resolution imaging spectroradiometer (Terra-Aqua/NASA) aerosol
      optical properties. The semi-empirical approach adopted takes into account
      PM(2.5) sampling and meteorological descriptions of the area studied, as
      simulated by MM5, to infer aerosol optical properties to PM projection
      coefficients. Daily maps of satellite-based PM(2.5) concentrations over northern
      Italy are derived. Monthly average values were compared with in situ PM(2.5)
      samplings showing good agreement. Ozone monitoring instrument (OMI) (Aura/NASA)
      NO(2) tropospheric contents are merged using the GAMES chemical model
      simulations. The method employs a weighted rescaling of the model column in the
      troposphere according to the OMI observations. The weightings take into account
      measurement errors and model column variances within the satellite ground pixel.
      The obtained ground-level concentrations of NO(2) show good agreement with the
      environmental agencies' in situ.

PMID- 19843551
TI  - Coronary revascularization in a child with homozygous familial
      hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is a genetic disease caused by a mutation in
      low-density lipoprotein (LDL) receptor gene. It causes various presentations
      including tendon xanthoma and cardiac manifestations. Herein, we present a young
      patient with homozygous FH (HFH) who presented with dyspnea and chest pain caused
      by coronary arteries stenosis and treated with coronary artery bypass graft
      (CABG) surgery at the age of 13 years. To the best of our knowledge, he is one of
      the youngest patients in the English language literature for whom coronary
      revascularization has been done in childhood.

PMID- 19843552
TI  - Uninsured adults with chronic conditions or disabilities: gaps in public
      insurance programs.
AB  - Among nonelderly U.S. adults (ages 25-61), uninsurance rates increased from 13.7
      percent in 2000 to 16.0 percent in 2005. Despite the existence of public
      insurance programs, rates remained high for low-income people reporting serious
      health conditions (25 percent across years) or disabilities (15 percent).
      Residents of southern states had even higher rates (32 percent with health
      conditions, 22 percent with disabilities). Those who did not belong to a
      federally mandated Medicaid eligibility category were about twice as likely as
      others to be uninsured overall, and uninsurance among this group increased more
      rapidly over time. These regional and categorical differences reflect gaps in
      current policy that pose challenges for incremental health reform.

PMID- 19843553
TI  - Hypertension, diabetes, and elevated cholesterol among insured and uninsured U.S.
      adults.
AB  - In this paper we explore whether uninsured Americans with three chronic
      conditions were less likely than the insured to be aware of their illness or to
      have it controlled. Among those with diabetes and elevated cholesterol, the
      uninsured were more often undiagnosed. Among hypertensives and people with
      elevated cholesterol, the uninsured more often had uncontrolled conditions.
      Undiagnosed and uncontrolled chronic illness, which is common among insured
      people, is even more frequent among the uninsured.

PMID- 19843554
TI  - Implantable cardioverter defibrillator and competitive sport participation.

PMID- 19843555
TI  - Abnormal left ventricular relaxation in patients with long QT syndrome.

PMID- 19843556
TI  - HIV vaccine trial results--an opening for further research.

PMID- 19843558
TI  - To drink or not to drink? Explaining "contradictory findings" in fluid
      replacement and exercise performance: evidence from a more valid model for real
      life competition.

PMID- 19843559
TI  - Detecting over-age players using wrist MRI: science partnering with sport to
      ensure fair play.

PMID- 19843557
TI  - Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.
AB  - BACKGROUND: The development of a safe and effective vaccine against the human
      immunodeficiency virus type 1 (HIV-1) is critical to pandemic control. METHODS:
      In a community-based, randomized, multicenter, double-blind, placebo-controlled
      efficacy trial, we evaluated four priming injections of a recombinant canarypox
      vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant
      glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo
      injections were administered to 16,402 healthy men and women between the ages of
      18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers,
      primarily at heterosexual risk for HIV infection, were monitored for the
      coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the
      6-month vaccination series and every 6 months thereafter for 3 years. RESULTS: In
      the intention-to-treat analysis involving 16,402 subjects, there was a trend
      toward the prevention of HIV-1 infection among the vaccine recipients, with a
      vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; P=0.08).
      In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was
      26.2% (95% CI, -13.3 to 51.9; P=0.16). In the modified intention-to-treat
      analysis involving 16,395 subjects (with the exclusion of 7 subjects who were
      found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2%
      (95% CI, 1.1 to 52.1; P=0.04). Vaccination did not affect the degree of viremia
      or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently
      diagnosed. CONCLUSIONS: This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce
      the risk of HIV infection in a community-based population with largely
      heterosexual risk. Vaccination did not affect the viral load or CD4+ count in
      subjects with HIV infection. Although the results show only a modest benefit,
      they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.)

PMID- 19843560
TI  - An automated and multiplexed method for high throughput peptide immunoaffinity
      enrichment and multiple reaction monitoring mass spectrometry-based
      quantification of protein biomarkers.
AB  - There is an urgent need for quantitative assays in verifying and validating the
      large numbers of protein biomarker candidates produced in modern "-omics"
      experiments. Stable isotope standards with capture by anti-peptide antibodies
      (SISCAPA) has shown tremendous potential to meet this need by combining peptide
      immunoaffinity enrichment with quantitative mass spectrometry. In this study, we
      describe three significant advances to the SISCAPA technique. First, we develop a
      method for an automated magnetic bead-based platform capable of high throughput
      processing. Second, we implement the automated method in a multiplexed SISCAPA
      assay (nine targets in one assay) and assess the performance characteristics of
      the multiplexed assay. Using the automated, multiplexed platform, we demonstrate
      detection limits in the physiologically relevant ng/ml range (from 10 microl of
      plasma) with sufficient precision (median coefficient of variation, 12.6%) for
      quantifying biomarkers. Third, we demonstrate that enrichment of peptides from
      larger volumes of plasma (1 ml) can extend the limits of detection to the low
      pg/ml range of protein concentration. The method is generally applicable to any
      protein or biological specimen of interest and holds great promise for analyzing
      large numbers of biomarker candidates.

PMID- 19843562
TI  - Withdrawal of consent by sperm donors.

PMID- 19843561
TI  - Proteomics analysis reveals overlapping functions of clustered protocadherins.
AB  - The three tandem-arrayed protocadherin (Pcdh) gene clusters, namely Pcdh-alpha,
      Pcdh-beta, and Pcdh-gamma, play important roles in the development of the
      vertebrate central nervous system. To gain insight into the molecular action of
      PCDHs, we performed a systematic proteomics analysis of PCDH-gamma-associated
      protein complexes. We identified a list of 154 non-redundant proteins in the PCDH
      gamma complexes. This list includes nearly 30 members of clustered Pcdh-alpha, 
      beta, and -gamma families as core components of the complexes and additionally
      over 120 putative PCDH-associated proteins. We validated a selected subset of
      PCDH-gamma-associated proteins using specific antibodies. Analysis of the
      identities of PCDH-associated proteins showed that the majority of them overlap
      with the proteomic profile of postsynaptic density preparations. Further analysis
      of membrane protein complexes revealed that several validated PCDH-gamma
      associated proteins exhibit reduced levels in Pcdh-gamma-deficient brain tissues.
      Therefore, PCDH-gamma s are required for the integrity of the complexes. However,
      the size of the overall complexes and the abundance of many other proteins
      remained unchanged, raising a possibility that PCDH-alphas and PCDH-betas might
      compensate for PCDH-gamma function in complex formation. As a test of this idea,
      RNA interference knockdown of both PCDH-alphas and PCDH-gamma s showed that PCDHs
      have redundant functions in regulating neuronal survival in the chicken spinal
      cord. Taken together, our data provide evidence that clustered PCDHs coexist in
      large protein complexes and have overlapping functions during vertebrate neural
      development.

PMID- 19843564
TI  - Alcohol use in South Asians in the UK.

PMID- 19843565
TI  - Supervised exercise therapy versus usual care for patellofemoral pain syndrome:
      an open label randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of supervised exercise therapy compared
      with usual care with respect to recovery, pain, and function in patients with
      patellofemoral pain syndrome. DESIGN: Open label randomised controlled trial.
      SETTING: General practice and sport physician practice. PARTICIPANTS: Patients
      with a new episode of patellofemoral pain syndrome recruited by their general
      practitioner or sport physician. INTERVENTIONS: The intervention group received a
      standardised exercise programme for 6 weeks tailored to individual performance
      and supervised by a physical therapist, and were instructed to practise the
      tailored exercises at home for 3 months. The control group were assigned usual
      care, which comprised a "wait and see" approach of rest during periods of pain
      and refraining from pain provoking activities. Both the intervention group and
      the control group received written information about patellofemoral pain syndrome
      and general instructions for home exercises. MAIN OUTCOME MEASURES: The primary
      outcomes were self reported recovery (7 point Likert scale), pain at rest and
      pain on activity (0-10 point numerical rating scale), and function (0-100 point
      Kujala patellofemoral score) at 3 months and 12 months follow-up. RESULTS: A
      total of 131 participants were included in the study: 65 in the intervention
      group and 66 in the control group. After 3 months, the intervention group showed
      better outcomes than the control group with regard to pain at rest (adjusted
      difference -1.07, 95% confidence interval -1.92 to -0.22; effect size 0.47), pain
      on activity (-1.00, -1.91 to -0.08; 0.45), and function (4.92, 0.14 to 9.72;
      0.34). At 12 months, the intervention group continued to show better outcomes
      than the control group with regard to pain (adjusted difference in pain at rest 
      1.29, -2.16 to -0.42; effect size 0.56; pain on activity -1.19, -2.22 to -0.16;
      effect size 0.54), but not function (4.52, -0.73 to 9.76). A higher proportion of
      patients in the exercise group than in the control group reported recovery (41.9%
      v 35.0% at 3 months and 62.1% v 50.8% at 12 months), although the differences in
      self reported recovery between the two groups were not statistically significant.
      Predefined subgroup analyses revealed that patients recruited by sport physicians
      (n=30) did not benefit from the intervention, whereas those recruited by general
      practitioners (n=101) showed significant and clinically relevant differences in
      pain and function in favour of the intervention group. CONCLUSION: Supervised
      exercise therapy resulted in less pain and better function at short term and long
      term follow-up compared with usual care in patients with patellofemoral pain
      syndrome in general practice. Exercise therapy did not produce a significant
      difference in the rate of self reported recovery. TRIAL REGISTRATION:
      ISRCTN83938749.

PMID- 19843566
TI  - Inconvenient truths about supplier induced demand and unwarranted variation in
      medical practice.

PMID- 19843567
TI  - Using patient experience within pay for performance programmes.

PMID- 19843570
TI  - H1N1 pandemic flu found to cause viral pneumonia in severe cases, says WHO.

PMID- 19843573
TI  - Pivotal advance: glycyrrhizin restores the impaired production of beta-defensins
      in tissues surrounding the burn area and improves the resistance of burn mice to
      Pseudomonas aeruginosa wound infection.
AB  - The decreased production of antimicrobial peptides in tissues surrounding the
      burn sites has been described in patients with severe burn injury. Small numbers
      of Pseudomonas aeruginosa spread easily to the whole body of burn mice when
      infected at burn site tissues. Gr-1(+)CD11b(+) cells, demonstrated in tissues
      surrounding the burn site, are inhibitory on the production of antimicrobial
      peptides by EK. In this paper, the decreased production of antimicrobial peptides
      by EK influenced by Gr-1(+)CD11b(+) cells was shown to be restored by
      glycyrrhizin. CCL2 and IL-10 were determined to be effector soluble factors for
      the suppressor activities of Gr-1(+)CD11b(+) cells on antimicrobial peptide
      production by EK. However, Gr-1(+)CD11b(+) cells, which were treated previously
      with glycyrrhizin, did not produce these soluble factors. Also, sepsis stemming
      from P. aeruginosa burn-site infection was not demonstrated in burn mice treated
      with glycyrrhizin. These results suggest that through the improved production of
      antimicrobial peptides in tissues surrounding the burn area, sepsis stemming from
      P. aeruginosa wound infection is controllable by glycyrrhizin in severely burned
      mice.

PMID- 19843574
TI  - Signaling through TLR7 enhances the immunosuppressive activity of murine
      CD4+CD25+ T regulatory cells.
AB  - Although signaling through certain TLRs is known to modulate the function of T
      lymphocytes, the effect of TLR7 stimulation on CD4(+)CD25(+) T(reg) cell activity
      has not yet been elucidated. In this study, we show that mouse CD4(+)CD25(+)
      T(reg) cells express TLR7 mRNA and protein. We therefore used the TLR7 agonists
      imiquimod, gardiquimod, and single-stranded poly(U) to show that TLR7 stimulation
      enhanced the ability of murine T(reg) cells to suppress anti-CD3/anti-CD28 mAb
      coated bead-stimulated proliferation of syngeneic CD4(+)CD25(-) T(resp) cells. In
      contrast, imiquimod failed to enhance the suppressor function of T(reg) cells
      from mice deficient in the MyD88 adaptor protein involved in TLR7 and other TLR
      signal transduction. Imiquimod increased murine T(reg) cell-mediated suppression
      of T(resp) cell proliferation induced by anti-TCRbeta mAb in the presence of
      syngeneic BMDCs, and T(reg) cells from gardiquimod-treated mice exhibited
      enhanced in vitro suppressor function. Moreover, levels of T(resp) cell-secreted
      IL-2 and IFN-gamma were reduced further in the presence of T(reg) cells plus
      imiquimod in comparison with T(reg) cells alone. In addition, imiquimod treatment
      increased CD25 expression by T(reg) cells and caused exogenous IL-2 to enhance
      T(reg) cell suppressor function. Furthermore, combined treatment with imiquimod
      and IL-2 increased Foxp3 expression by T(reg) cells. Collectively, these findings
      suggest that TLR7 signaling enhanced the suppressor function of T(reg) cells by
      sensitizing T(reg) cells to IL-2-induced activation. We speculate that TLR7
      stimulated enhancement of T(reg) cell suppressor function may modulate host T
      cell responses against ssRNA viruses.

PMID- 19843575
TI  - Immunopathogenesis of polymicrobial otitis media.
AB  - OM, or inflammation of the middle ear, is a highly prevalent infection in
      children worldwide. OM is a multifactorial disease with multiple risk factors,
      including preceding or concurrent viral URT infection. Hence, OM is also a
      polymicrobial disease. The mechanisms by which viruses predispose to bacterial OM
      are replete; however, all are predicated on the general principle of compromise
      of primary host airway defenses. Thus, despite an as-yet incomplete understanding
      of the molecular mechanisms involved in bacterial superinfection of a virus
      compromised respiratory tract, the URT viruses are known to induce histopathology
      of airway mucosal epithelium, up-regulate expression of eukaryotic receptors used
      for bacterial adherence, alter the biochemical and rheological properties of
      airway mucus, and affect innate and acquired host immune functions, among others.
      Although discussed here in the context of OM, during preceding or concurrent
      viral infection of the human respiratory tract, viral impairment of airway
      defenses and the resulting predisposition to subsequent bacterial coinfection are
      also known to be operational in the mid and lower airway as well.

PMID- 19843576
TI  - Antagonistic roles of four SR proteins in the biosynthesis of alternatively
      spliced tissue factor transcripts in monocytic cells.
AB  - Following recruitment to solid tissues, peripheral blood monocytes express a
      number of proinflammatory molecules including TF, a trigger of coagulation that
      also promotes cell-cell interactions and tissue remodeling. Monocytes express two
      forms of TF: flTF, a highly coagulant transmembrane form, and asTF, a highly
      proangiogenic, soluble TF form. Biosynthesis of the two TF forms occurs via
      alternative processing of exon 5 during pre-mRNA splicing. Its inclusion results
      in flTF mRNA and its exclusion, asTF mRNA. We developed a splicing reporter
      system recently and determined that two spliceosomal constituents, SR proteins
      ASF/SF2 and SRp55, play a pivotal role in exon 5 inclusion. In this report, we
      show for the first time that two other SR proteins expressed in human monocytes,
      SRp40 and SC35, antagonize ASF/SF2 and SRp55 by competing for binding to certain
      sites in exon 5, thereby promoting TF exon 5 exclusion, an event unique to asTF
      biosynthesis. We also show that the intron preceding TF exon 5 possesses
      characteristics rarely found in U2 introns. Our findings indicate that modulation
      of TF pre-mRNA splicing can be accomplished via modification of SR proteins'
      activity, facilitating development of novel therapeutic strategies to modulate
      the "TF profile" of monocytes/macrophages.

PMID- 19843577
TI  - Decreased ERK and JNK signaling contribute to gene overexpression in "senescent"
      CD4+CD28- T cells through epigenetic mechanisms.
AB  - An inflammatory and cytotoxic CD4+CD28- T cell subset infiltrates atherosclerotic
      plaques and is implicated in plaque rupture and myocardial infarctions. This
      pathologic subset develops with replicative stress and is found in patients with
      chronic inflammatory diseases such as RA as well as with aging. CD4+CD28- cells
      overexpress genes normally suppressed by DNA methylation in CD4+CD28+ T cells,
      such as KIR, perforin, and CD70. How this subset over expresses methylation
      sensitive genes is unknown. DNA methylation patterns are maintained in
      proliferating cells by Dnmts, which are up-regulated during mitosis by the ERK
      and JNK signaling pathways. We hypothesized that defects in these signaling
      pathways contribute to altered gene expression in human CD4+CD28- cells through
      effects on DNA methylation. We report that signaling through the ERK and JNK
      pathways is decreased in CD4+CD28- relative to CD4+CD28+ cells from the same
      individuals and that ERK and JNK pathway inhibition decreases Dnmt1 and -3a
      levels, which in turn, causes demethylation and overexpression of the TNFSF7
      (CD70) gene. We also report that CD4+CD28- T cells overexpress PP5, a stress
      induced inhibitor of the ERK and JNK signaling pathways that may contribute to
      the signaling defects. We conclude that decreased ERK and JNK signaling in the
      CD4+CD28- subset, arising with replicative stress, can lead to the overexpression
      of normally suppressed genes through effects on Dnmts and consequently, chromatin
      structure.

PMID- 19843578
TI  - Antigen-induced Erk1/2 activation regulates Ets-1-mediated sensitization of CD8+
      T cells for IL-12 responses.
AB  - The presence of IL-12 during antigen stimulation instructs naive CD8+ T cells for
      long-term effector responses, but their mechanisms of collaboration are not
      understood completely. Herein, we report that CD8+ T cells (OT-I T cells)
      stimulated with antigen for a longer duration show enhanced sensitization to IL
      12 as a result of Erk1/2-dependent, increased Ets-1 phosphorylation and
      subsequent increases in IL-12Rbeta2 expression. Correspondingly, naive OT-I T
      cells stimulated by antigen for a longer duration in the presence of IL-12,
      irrespective of frequency of APCs, show robust effector maturation and mount long
      term antigen-recall responses upon adoptive transfer. These results identify the
      role of antigen strength-dependent Erk1/2 activation for Ets-1-mediated
      collaboration with IL-12 in CD8+ T cells.

PMID- 19843579
TI  - Monocyte heterogeneity underlying phenotypic changes in monocytes according to
      SIV disease stage.
AB  - Infection by HIV is associated with the expansion of monocytes expressing CD16
      antigens, but the significance of this in HIV pathogenesis is largely unknown. In
      rhesus macaques, at least three subpopulations of blood monocytes were identified
      based on their expression of CD14 and CD16: CD14(high)CD16(-),
      CD14(high)CD16(low), and CD14(low)CD16(high). The phenotypes and functions of
      these subpopulations, including CD16(+) monocytes, were investigated in normal,
      uninfected rhesus macaques and macaques that were infected with SIV or chimeric
      SHIV. To assess whether these different monocyte subpopulations expand or
      contract in AIDS pathogenesis, we conducted a cross-sectional study of 54 SIV- or
      SHIV-infected macaques and 48 uninfected controls. The absolute numbers of
      monocyte populations were examined in acutely infected animals, chronically
      infected animals with no detectable plasma virus RNA, chronically infected
      animals with detectable plasma virus RNA, and animals that died with AIDS. The
      absolute numbers of CD14(high)CD16(low) and CD14(low)CD16(high) monocytes were
      elevated significantly in acutely infected animals and chronically infected
      animals with detectable plasma virus RNA compared with uninfected controls.
      Moreover, a significant, positive correlation was evident between the number of
      CD14(high)CD16(low) or CD14(low)CD16(high) monocytes and plasma viral load in the
      infected cohort. These data show the dynamic changes of blood monocytes, most
      notably, CD14(high)CD16(low) monocytes during lentiviral infection, which are
      specific to disease stage.

PMID- 19843580
TI  - MicroRNAs: a complex regulatory network drives the acquisition of malignant cell
      phenotype.
AB  - Several lines of evidence indicate that tumorigenesis is a complex multistep
      process, and that most, if not all, cancers acquire the same set of functional
      capabilities during development and progression, albeit through various
      mechanistic strategies. Increasing data show an important role of microRNAs
      (miRNAs or miRs) in regulating various aspects of cancer biology. This review
      describes the role of microRNAs during the multiple steps that drive the
      progressive transformation of normal cells into highly malignant derivatives,
      outlining the role of microRNAs in regulating the common hallmarks of
      tumorigenesis: self-sufficiency in growth signals, insensitivity to antigrowth
      signals, abnormal apoptosis, limitless replicative potential, induction and
      sustained angiogenesis, and tissue invasion and metastasis. Recent evidence
      suggests an important role of microRNAs in the regulation of the expression of
      most genes regulating and coordinating a wide variety of processes in endocrine
      glands. We will highlight microRNAs of potential relevance to endocrine tumors
      and hormone-dependent cancers. Through this overview of how microRNAs regulate
      multiple targets and entire pathways, we will provide insight into the potential
      to develop new molecular microRNA-targeted therapies for endocrine tumors.

PMID- 19843582
TI  - Reprogramming of Xist against the pluripotent state in fusion hybrids.
AB  - The fusion of somatic cells with pluripotent cells results in the generation of
      pluripotent hybrid cells. Because the ;memory' of somatic cells seems to be
      erased during fusion-induced reprogramming, genetic reprogramming is thought to
      be a largely unidirectional process. Here we show that fusion-induced
      reprogramming, which brings about the formation of pluripotent hybrids, does not
      always follow a unidirectional route. Xist is a unique gene in that it is
      reprogrammed to the state of somatic cells in fusion-induced pluripotent hybrids.
      In hybrids formed from the cell fusion of embryonal carcinoma cells (ECCs) with
      male neural stem cells (mNSCs), the Xist gene was found to be reprogrammed to the
      somatic cell state, whereas the pluripotency-related and tissue-specific marker
      genes were reprogrammed to the pluripotent cell state. Specifically, Xist is not
      expressed in hybrids, because the ;memory' of the somatic cell has been retained
      (i.e. mNSCs do not exhibit Xist expression) and that of the pluripotent cell
      erased (i.e. inactivation of the partially active Xist gene of ECCs, complete
      methylation of the Xist region). The latter phenomenon is induced by male, but
      not by female, NSCs.

PMID- 19843581
TI  - Dynamics and molecular interactions of linker of nucleoskeleton and cytoskeleton
      (LINC) complex proteins.
AB  - The linker of nucleoskeleton and cytoskeleton (LINC) complex is situated in the
      nuclear envelope and forms a connection between the lamina and cytoskeletal
      elements. Sun1, Sun2 and nesprin-2 are important components of the LINC complex.
      We expressed these proteins fused to green fluorescent protein in embryonic
      fibroblasts and studied their diffusional mobilities using fluorescence recovery
      after photobleaching. We show that they all are more mobile in embryonic
      fibroblasts from mice lacking A-type lamins than in cells from wild-type mice.
      Knockdown of Sun2 also increased the mobility of a short, chimeric form of
      nesprin-2 giant (mini-nesprin-2G), whereas the lack of emerin did not affect the
      mobility of Sun1, Sun2 or mini-nesprin-2G. Fluorescence resonance energy transfer
      experiments showed Sun1 to be more closely associated with lamin A than is Sun2.
      Sun1 and Sun2 had similar affinity for the nesprin-2 KASH domain in plasmon
      surface resonance (Biacore) experiments. This affinity was ten times higher than
      that previously reported between nesprin-2 and actin. Deletion of the actin
      binding domain had no effect on mini-nesprin-2G mobility. Our data support a
      model in which A-type lamins and Sun2 anchor nesprin-2 in the outer nuclear
      membrane, whereas emerin, Sun1 and actin are dispensable for this anchoring.

PMID- 19843583
TI  - HSCARG inhibits activation of NF-kappaB by interacting with IkappaB kinase-beta.
AB  - HSCARG is a recently identified human NADPH sensor. Our previous studies have
      shown that HSCARG can affect NO production and cell viability, but the signal
      pathway mediated by this protein is unknown. Here, we show that HSCARG is
      involved in the NF-kappaB signaling pathway and find that HSCARG suppresses TNF-
      and IL1-induced NF-kappaB activation in a dose-dependent manner. Co
      immunoprecipitation and immunofluorescence analyses demonstrate that HSCARG
      interacts and colocalizes with IKKbeta. HSCARG inhibits the phosphorylation of
      IKKbeta and further blocks the degradation of IkappaBalpha, the substrate of
      IKKbeta, which retains NF-kappaB in the cytoplasm and suppresses its activity. In
      addition, our data indicate that IKKbeta is required for HSCARG-inhibited NF
      kappaB activation. Our findings delineate a pathway by which HSCARG negatively
      regulates NF-kappaB activation.

PMID- 19843584
TI  - Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA
      accumulation during DNA-replication stress.
AB  - ATR is an essential kinase activated in response to DNA-replication stress, with
      a known target being the RPA2 subunit of human replication protein A (RPA). We
      find that S33-RPA2 phosphorylation by ATR occurs primarily in the late-S and G2
      phases, probably at sites of residual stalled DNA-replication forks, with S33-P
      RPA2 contained within nuclear repair centers. Although cells in which endogenous
      RPA2 was ;replaced' with an RPA2 protein with mutations T21A and S33A (T21A/S33A
      RPA) had normal levels of DNA replication under non-stress conditions, the mutant
      cells were severely deficient in the amount of DNA synthesis occurring during
      replication stress. These cells also had abnormally high levels of chromatin
      bound RPA, indicative of increased amounts of single-stranded DNA (ssDNA) and
      showed defective recovery from stress. Cells replaced with the mutant RPA2 also
      generated G1 cells with a broader DNA distribution and high levels of apoptosis
      following stress, compared with cells expressing wild-type RPA2. Surprisingly,
      cells expressing the wild-type RPA2 subunit had increased levels of stress
      dependent DNA breaks. Our data demonstrate that RPA phosphorylation at the T21
      and S33 sites facilitates adaptation of a DNA-replication fork to replication
      stress.

PMID- 19843585
TI  - KazrinE is a desmosome-associated liprin that colocalises with acetylated
      microtubules.
AB  - Kazrin is a widely expressed, evolutionarily conserved cytoplasmic protein that
      binds the cytolinker protein periplakin. Multiple functions of kazrin have been
      reported, including regulation of desmosome assembly, embryonic tissue
      morphogenesis and epidermal differentiation. Here, we identify kazrinE as a
      kazrin isoform that contains a liprin-homology domain (LHD) and forms complexes
      with kazrinA, kazrinB and kazrinC. As predicted from the presence of the LHD,
      kazrinE can associate with the leukocyte common antigen-related (LAR) protein
      tyrosine phosphatase in a phosphorylation-dependent manner. When overexpressed in
      epidermal keratinocytes, kazrinE induces changes in cell shape and stimulates
      terminal differentiation. Like the other kazrin isoforms, kazrinE localises to
      the nucleus and desmosomes. However, in addition, kazrinE associates with
      stabilised microtubules via its LHD. During terminal differentiation, the
      keratinocyte microtubule network undergoes extensive reorganisation; in
      differentiating keratinocytes, endogenous kazrinE colocalises with microtubules,
      but periplakin does not. We speculate that the kazrinE-microtubule interaction
      contributes to the mechanism by which kazrin regulates desmosome formation and
      epidermal differentiation.

PMID- 19843586
TI  - Clathrin-independent internalization of normal cellular prion protein in
      neuroblastoma cells is associated with the Arf6 pathway.
AB  - To understand the role of clathrin-mediated endocytosis in the internalization of
      normal cellular prion protein (PrP(c)) in neuronal cells, N2a cells were depleted
      of clathrin by RNA interference. PrP(c) internalization via the constitutive
      endocytic pathway in the absence of Cu(2+) and the stimulated pathway in the
      presence of Cu(2+) were measured in both control and clathrin-depleted cells.
      Depletion of clathrin had almost no effect on the internalization of PrP(c)
      either in the presence or absence of Cu(2+), in contrast to the marked reduction
      observed in transferrin uptake. By contrast, the internalization of PrP(c) was
      inhibited by the raft-disrupting drugs filipin and nystatin, and by the dominant
      negative dynamin-1 mutant dynamin-1 K44A, both in the presence and absence of
      Cu(2+). The internalized PrP(c) was found to colocalize with cargo that traffic
      in the Arf6 pathway and in large vacuoles in cells expressing the Arf6 dominant
      active mutant. These results show that PrP(c) is internalized in a clathrin
      independent pathway that is associated with Arf6.

PMID- 19843588
TI  - Polymorphisms in the promoter regions of matrix metalloproteinases 1 and 3 and
      cancer risk: a meta-analysis of 50 case-control studies.
AB  - Matrix metalloproteinase (MMP) 1 and MMP3 are enzymes that degrade the
      extracellular matrix and have been implicated to play an important role in cancer
      development. Many studies have been carried out on the association between
      polymorphisms of MMP1 -1607 1G>2G and MMP3 -1171 5A>6A and cancer risk. However,
      results from these studies remain inconclusive. Here, we performed a meta
      analysis of >38 000 subjects to better assess the purported associations. For
      MMP1, -1607 2G/2G genotype carriers were found to have an increased risk of
      colorectal cancer [2G/2G versus 2G/1G + 1G/1G, odds ratio (OR) = 1.48, 95%
      confidence interval (CI) (1.26-1.74), P(heterogeneity) = 0.066, I(2) = 49.3%],
      head and neck cancer [2G/2G versus 2G/1G + 1G/1G, OR = 1.61, 95% CI (1.26-2.07),
      P(heterogeneity) = 0.002, I(2) = 64.7%] and renal cancer [2G/2G versus 2G/1G +
      1G/1G, OR = 1.82, 95% CI (1.38-2.39), P(heterogeneity) = 0.589, I(2) = 0.0%]
      risk. For MMP3, no association was found between -1171 5A>6A polymorphism and
      cancer risk in the overall group [6A versus 5A, OR = 1.00, 95% CI (0.95-1.05),
      P(heterogeneity) = 0.124, I(2) = 24.9%] and individual cancer subgroups, but
      stratified analysis by smoking status showed that this polymorphism had different
      effects on smokers and non-smokers under recessive genetic model. In summary, our
      study suggests that MMP1 -1607 2G may be associated with an increased cancer risk
      for certain types of cancers, MMP3 -1171 5A>6A may not be a major risk factor for
      cancer, but it may be modified by certain environmental factors. Future studies
      with larger sample sizes are warranted to further evaluate these associations in
      more detail.

PMID- 19843589
TI  - Further evaluation of a flow cytometric in vitro micronucleus assay in CHO-K1
      cells: a reliable platform that detects micronuclei and discriminates apoptotic
      bodies.
AB  - The in vitro micronucleus (MN) assay is widely used to assess genotoxic potential
      of the test substances by measuring frequency of MN in cultured mammalian cells.
      Traditionally, MN frequency has been determined by microscopy. In recent years, a
      flow cytometric method for enumeration of MN has been developed, which
      significantly shortens analysis time and enhances assay throughput. However, a
      major concern has been raised that the MN results obtained from flow cytometry
      can be impacted by chromatin bodies produced during apoptosis or necrosis. In
      this work, we further evaluated this flow cytometry-based in vitro MN assay with
      CHO-K(1) cells in a 24-well platform. Our results showed that the MN frequency
      determined using the flow cytometric method was highly correlated with the
      microscopy results. Importantly, several non-genotoxic apoptosis inducers or
      cytotoxins that have been previously reported to produce 'artificial positives'
      in various in vitro genotoxicity tests were evaluated in this system. As a
      result, these non-genotoxic cytotoxins did not produce false-positive MN response
      in the flow cytometric system in CHO-K(1) cells when cytotoxicity was <50 +/-
      10%. Moreover, a total of 21 compounds were evaluated in this work, including
      direct or indirect clastogens, aneugens and non-genotoxic chemicals. A
      sensitivity of 83.3% and a specificity of 100% were obtained from the compounds
      we tested. Finally, significant increase of incidents in the hypodiploid region,
      an aneugenic signature, was confirmed in our evaluation. In conclusion, the flow
      cytometric in vitro MN assay is a reliable method that can be used to detect
      clastogenic or aneugenic potential of the test substances in CHO-K(1) cells.

PMID- 19843587
TI  - Xenopus delta-catenin is essential in early embryogenesis and is functionally
      linked to cadherins and small GTPases.
AB  - Catenins of the p120 subclass display an array of intracellular localizations and
      functions. Although the genetic knockout of mouse delta-catenin results in mild
      cognitive dysfunction, we found severe effects of its depletion in Xenopus. delta
      catenin in Xenopus is transcribed as a full-length mRNA, or as three (or more)
      alternatively spliced isoforms designated A, B and C. Further structural and
      functional complexity is suggested by three predicted and alternative translation
      initiation sites. Transcript analysis suggests that each splice isoform is
      expressed during embryogenesis, with the B and C transcript levels varying
      according to developmental stage. Unlike the primarily neural expression of delta
      catenin reported in mammals, delta-catenin is detectable in most adult Xenopus
      tissues, although it is enriched in neural structures. delta-catenin associates
      with classical cadherins, with crude embryo fractionations further revealing non
      plasma-membrane pools that might be involved in cytoplasmic and/or nuclear
      functions. Depletion of delta-catenin caused gastrulation defects, phenotypes
      that were further enhanced by co-depletion of the related p120-catenin. Depletion
      was significantly rescued by titrated p120-catenin expression, suggesting that
      these catenins have shared roles. Biochemical assays indicated that delta-catenin
      depletion results in reduced cadherin levels and cell adhesion, as well as
      perturbation of RhoA and Rac1. Titrated doses of C-cadherin, dominant-negative
      RhoA or constitutively active Rac1 significantly rescued delta-catenin depletion.
      Collectively, our experiments indicate that delta-catenin has an essential role
      in amphibian development, and has functional links to cadherins and Rho-family
      GTPases.

PMID- 19843590
TI  - An aphidicolin-block nucleotide excision repair assay measuring DNA incision and
      repair capacity.
AB  - The objective of the present study was to develop a cellular phenotype assay for
      nucleotide excision repair (NER), using benzo[a]pyrene diol epoxide (BPDE) as
      model mutagen. Since in vitro exposure to BPDE may lead to DNA strand breaks
      resulting from both direct interaction with DNA and incisions introduced by the
      repair enzymes, we aimed to discriminate between both types of breaks using the
      comet assay and quantified the DNA strand breaks after in vitro challenge of
      peripheral blood mononucleated cells (PBMCs) with BPDE in the presence or absence
      of the DNA polymerase inhibitor aphidicolin (APC). The assay was performed with a
      low (0.5 microM) and a high (2.5 microM) BPDE concentration. The individual NER
      capacity was defined as the amount of DNA damage induced by BPDE in presence of
      APC, diminished with the damage induced by BPDE and APC alone. First, the assay
      was applied to a NER-deficient human fibroblast cell line (XPA-/-) to validate
      the methodology. Lower repair capacity and a higher amount of BPDE-induced DNA
      adducts were observed for the XPA-/- fibroblasts as compared to the wild-type
      fibroblasts. Repeated experiments on PBMCs from four donors showed low intra
      individual, intra-experimental and inter-assay variation for both concentrations,
      indicating the reliability of the method. To assess the inter-individual
      variation, the assay was applied to PBMCs from 22 donors, comparing the repair
      capacity after exposure to 0.5 microM (N = 10) and 2.5 microM (N = 12) BPDE. The
      repair capacity showed a higher inter-individual variation as compared to the
      intra-individual variation. Moreover, this difference was more pronounced using
      the low concentration. All these results indicate the adequacy of the method
      using this low concentration. Further improvement, however, should be recommended
      by applying the study with low BPDE concentration in a larger population and
      taking into account the relevant genotypes for NER.

PMID- 19843591
TI  - On the future of biology.
AB  - Biology is driven by two strategies of research. The first, using functional
      studies at the molecule-to-organism transitions, utilizes the principle that for
      every problem in biology, there is an organism ideal for its solution. The
      second, comparative and evolutionary in orientation, consists of thorough studies
      of every biological aspect of a given taxonomic group of species and follows the
      principle inverse to the first that for every organism, there is a problem to the
      solution for which it is ideally suited. The two approaches are complementary and
      of increased connectivity to each other. In passing from the traditional,
      intensely focused reductionist approach of 20th century biology to a more
      synthetic and authentically holistic phase, new emphasis will be placed on the
      major transitions between levels of biological organizations and onto processes
      of multilevel evolution by which they have been achieved.

PMID- 19843592
TI  - Predicting virus evolution: the relationship between genetic robustness and
      evolvability of thermotolerance.
AB  - Evolutionary biologists often seek to infer historical patterns of relatedness
      among organisms using phylogenetic methods and to gauge the evolutionary
      processes that determine variation among individuals in extant populations. But
      relatively less effort is devoted to making evolutionary biology a truly
      predictive science, where future evolutionary events are precisely foreseen.
      Accurate predictions of evolvability would be particularly useful in the
      evolution of infectious diseases, such as the ability to preemptively address the
      challenge of pathogens newly emerging in humans and other host populations.
      Experimental evolution of microbes allows the possibility to rigorously test
      hypotheses regarding pathogen evolvability. Here, we review how genetic
      robustness was a useful predictor in gauging which variants of RNA virus varphi6
      should evolve faster in a novel high-temperature environment. We also present new
      data on the relative survival of robust and brittle viruses across elevated
      temperatures and durations of ultraviolet exposure, to infer a possible mechanism
      for robustness. Our work suggests that virus adaptability in a new environment
      can be predicted given knowledge of virus canalization in the face of mutational
      input. These results hint that accurate predictions of virus evolvability are a
      realistic possibility, at least under circumstances of adaptive thermotolerance.

PMID- 19843593
TI  - Cooking and the human commitment to a high-quality diet.
AB  - For our body size, humans exhibit higher energy use yet reduced structures for
      mastication and digestion of food compared to chimpanzees, our closest living
      relatives. This suite of features suggests that humans are adapted to a high
      quality diet. Although increased consumption of meat during human evolution
      certainly contributed to dietary quality, meat-eating alone appears to be
      insufficient to support the evolution of these traits, because modern humans fare
      poorly on raw diets that include meat. Here, we suggest that cooking confers
      physical and chemical benefits to food that are consistent with observed human
      dietary adaptations. We review evidence showing that cooking facilitates
      mastication, increases digestibility, and otherwise improves the net energy value
      of plant and animal foods regularly consumed by humans. We also address the
      likelihood that cooking was adopted more than 250,000 years ago (kya), a period
      that we believe is sufficient in length for the proposed adaptations to have
      occurred. Additional experimental work is needed to help discriminate the
      relative contributions of cooking, meat eating, and other innovations such as
      nonthermal food processing in supporting the human transition toward dietary
      quality.

PMID- 19843595
TI  - Exploring the molecular landscape of host-parasite coevolution.
AB  - Host-parasite coevolution is a dynamic process that can be studied at the
      phenotypic, genetic, and molecular levels. Although much of what we currently
      know about coevolution has been learned through phenotypic measures, recent
      advances in molecular techniques have provided tools to greatly deepen this
      research. Both the availability of full-genome sequences and the increasing
      feasibility of high-throughput gene expression profiling are leading to the
      discovery of genes that have a key role in antagonistic interactions between
      naturally coevolving species. Identification of such genes can enable direct
      observation, rather than inference, of the host-parasite coevolutionary dynamic.
      The Daphnia magna-Pasteuria ramosa host-parasite model is a prime example of an
      interaction that has been well studied at the population and whole-organism
      levels, and much is known about genotype- and environment-specific interactions
      from a phenotypic perspective. Now, with the recent completion of genome
      sequences for two Daphnia species, and a transcriptomics project under way,
      coevolution between these two enemies is being investigated directly at the level
      of interacting genes.

PMID- 19843594
TI  - Evolution of insect dorsoventral patterning mechanisms.
AB  - The dorsoventral (DV) patterning of the early Drosophila embryo depends on
      Dorsal, a maternal sequence-specific transcription factor related to mammalian NF
      kappaB. Dorsal controls DV patterning through the differential regulation of
      approximately 50 target genes in a concentration-dependent manner. Whole-genome
      methods, including ChIP-chip and ChIP-seq assays, have identified approximately
      100 Dorsal target enhancers, and more than one-third of these have been
      experimentally confirmed via transgenic embryo assays. Despite differences in DV
      patterning among divergent insects, a number of the Dorsal target enhancers are
      located in conserved positions relative to the associated transcription units.
      Thus, the evolution of novel patterns of gene expression might depend on the
      modification of old enhancers, rather than the invention of new ones. As many as
      half of all Dorsal target genes appear to contain "shadow" enhancers: a second
      enhancer that directs the same or similar expression pattern as the primary
      enhancer. Preliminary studies suggest that shadow enhancers might help to ensure
      resilience of gene expression in response to environmental and genetic
      perturbations. Finally, most Dorsal target genes appear to contain RNA polymerase
      II (pol II) prior to their activation. Stalled pol II fosters synchronous
      patterns of gene activation in the early embryo. In contrast, DV patterning genes
      lacking stalled pol II are initially activated in an erratic or stochastic
      fashion. It is possible that stalled pol II confers fitness to a population by
      ensuring coordinate deployment of the gene networks controlling embryogenesis.

PMID- 19843596
TI  - A pilot study of comparison of BCPAP vs. VCPAP in preterm infants with early
      onset respiratory distress.
AB  - BACKGROUND: Bubble continuous positive airway pressure (BCPAP) is a low-cost
      nasal CPAP delivery system with potential benefits for developing nations. The
      objective of the study was to compare the efficacy and safety of BCPAP with
      ventilator CPAP (VCPAP) in preterm neonates with moderate respiratory distress.
      METHODS: In a pilot randomized controlled trial, 30 preterm neonates (gestation
      <37 weeks) with Silverman-Anderson score between 5 to 7 and oxygen requirement
      >30% within first 6 h of life were randomly allocated to BCPAP or VCPAP after
      informed parental consent. Proportion of neonates with success or failure, while
      using the allocated mode of CPAP delivery (primary outcome) was compared.
      RESULTS: The success rate was comparable [VCPAP: 80% (12/15) vs. BCPAP: 87%
      (13/15)] between the two groups. Dislodgement was commonest problem with equal
      frequency [10/15, (67%)] in each group. CONCLUSION: BCPAP appears to be a
      promising method of CPAP delivery in preterm neonates with moderate respiratory
      distress.

PMID- 19843597
TI  - The epidemiology of domestic injurious falls in a community dwelling elderly
      population: an outgrowing economic burden.
AB  - In Italy, more than 3 million people annually sustain a domestic injury; the
      elderly experience it the most. From a healthcare perspective, elderly falls are
      a major clinical issue with an outgrowing socioeconomic burden. The aim of the
      study was to evaluate the epidemiology of injurious falls in a community dwelling
      population, admitted to the emergency room (ER) because of a domestic injury, to
      assess the socioeconomic burden. Seventy-four hospitalized patients among 227
      were examined. Falls represented the main cause of admittance to the ER; the
      average cost for fall-related hospitalization was of ?5479.09.

PMID- 19843598
TI  - The impact of widowhood on Irish mortality due to suicide and accidents.
AB  - The impact of widowhood on suicide and accident mortality in Ireland was
      investigated using Poisson regression analysis applied to routine data relating
      to all 10 561 suicidal and accidental deaths of married or widowed persons aged
      at least 35 years in Ireland during 1986-2005. Mortality rates were almost always
      higher among the widowed and often by a 2-fold, statistically significant
      difference. The excess mortality was equivalent to 2083 or 57.6% of all suicidal
      or accidental deaths of widowed persons in 1986-2005. Routine contact with
      recently widowed persons by public health professionals may be warranted with a
      view to reducing their excess mortality.

PMID- 19843599
TI  - Organizational capacity for chronic disease prevention: a survey of Canadian
      public health organizations.
AB  - BACKGROUND: There are no national data on levels of organizational capacity
      within the Canadian public health system to reduce the burden of chronic disease.
      METHODS: Cross-sectional data were collected in a national survey (October 2004
      to April 2005) of all 216 national, provincial and regional-level organizations
      engaged in chronic disease prevention through primary prevention or healthy
      lifestyle promotion. Levels of organizational capacity (defined as skills and
      resources to implement chronic disease prevention programmes), potential
      determinants of organizational capacity and involvement in chronic disease
      prevention programming were compared in western, central and eastern Canada and
      across three types of organizations (formal public health organizations, non
      governmental organizations and grouped organizations). RESULTS: Forty percent of
      organizations were located in Central Canada. Approximately 50% were formal
      public health organizations. Levels of skill and involvement were highest for
      activities that addressed tobacco control and healthy eating; lowest for stress
      management, social determinants of health and programme evaluation. The few
      notable differences in skill levels by provincial grouping favoured Central
      Canada. Resource adequacy was rated low across the country; but was lowest in
      eastern Canada and among formal public health organizations. Determinants of
      organizational capacity (organizational supports and partnerships) were highest
      in central Canada and among grouped organizations. CONCLUSION: These data provide
      an evidence base to identify strengths and gaps in organizational capacity and
      involvement in chronic disease prevention programming in the organizations that
      comprise the Canadian public health system.

PMID- 19843600
TI  - Interrelationships between education, occupational class, income and sickness
      absence.
AB  - BACKGROUND: Socio-economic position measures, such as education, occupational
      class and income, are well-known determinants of health. However, previous
      studies have not paid attention to mutual interrelationships between these socio
      economic position measures and medically confirmed sickness absence. METHODS: The
      study is a register-based study. The participants were municipal employees of the
      City of Helsinki aged 25-59 years in 2003. There were 21,599 women and 5841 men
      participants. Three socio-economic position measures were used, namely three
      level education, four-level occupational class and gross individual income
      quartiles. Main outcome measure was medically confirmed sickness absence spells
      of 4 days or longer. Inequality indices were calculated using Poisson regression
      analysis. RESULTS: High education, occupational class and individual income were
      all consistently associated with lower sickness absence rates among both women
      and men. After mutual adjustment, education and occupational class remained
      independent determinants of sickness absence. The association of individual
      income with sickness absence was practically explained by temporally preceding
      education and occupational class. CONCLUSIONS: Our results indicate that
      education and occupational class-rather than income-are strong determinants of
      sickness absence. Education, occupational class and income are complementary
      socio-economic position measures. To better inform sickness absence policy,
      future studies should aim to establish whether the observed socio-economic
      differences reflect broader differences in ill-health, lifestyle and working
      conditions.

PMID- 19843601
TI  - Myelomatous pleural effusion.

PMID- 19843602
TI  - South Asian strokes: lessons from the St Mary's stroke database.
AB  - BACKGROUND: South Asians comprise the largest ethnic minority population in the
      UK. This subgroup is known to have an elevated risk of stroke. However, there is
      limited data on patterns of cerebrovascular disease and associated risk factors
      in this population. AIM: The aim of this study was to analyse differences in
      stroke subtype and risk factor profile between South Asian and White stroke
      patients admitted to a central London teaching hospital. DESIGN: Prospective
      database of all admissions to the St Mary's Hospital stroke unit. METHODS: We
      examined ethnicity, stroke subtype and risk factor profile of consecutive
      patients admitted to the stroke unit between 8 October 2003 and 14 February 2007.
      RESULTS: A total of 811 patients were identified of whom 736 had strokes. Four
      hundred and ninety-six (67%) occurred in the White subgroup, and 72 (10%) in the
      Asian subgroup. The South Asian subgroup was significantly younger (65 vs. 73
      years in the White subgroup; P < 0.001). They had higher rates of hypertension
      (age adjusted frequency 87% vs. 64%; P < 0.0001), diabetes (54% vs. 15%; P <
      0.0001), and hyperlipidaemia (70% vs. 45%; P = 0.001). There were lower rates of
      smoking (15% vs. 33%; P < 0.0001).There was a trend towards more lacunar infarcts
      and less total anterior circulation infarcts in South Asians, although after age
      adjustment this was not significant at the 5% level. CONCLUSION: The South Asian
      subgroup has shown important differences in risk factor profile compared with the
      White population. The higher frequency of hypertension, diabetes and
      hyperlipidaemia seen in this subgroup are an important consideration in designing
      secondary prevention programmes tailored specifically to this community.

PMID- 19843603
TI  - Palmar fasciitis and polyarthritis syndrome.

PMID- 19843604
TI  - TriTrypDB: a functional genomic resource for the Trypanosomatidae.
AB  - TriTrypDB (http://tritrypdb.org) is an integrated database providing access to
      genome-scale datasets for kinetoplastid parasites, and supporting a variety of
      complex queries driven by research and development needs. TriTrypDB is a
      collaborative project, utilizing the GUS/WDK computational infrastructure
      developed by the Eukaryotic Pathogen Bioinformatics Resource Center
      (EuPathDB.org) to integrate genome annotation and analyses from GeneDB and
      elsewhere with a wide variety of functional genomics datasets made available by
      members of the global research community, often pre-publication. Currently,
      TriTrypDB integrates datasets from Leishmania braziliensis, L. infantum, L.
      major, L. tarentolae, Trypanosoma brucei and T. cruzi. Users may examine
      individual genes or chromosomal spans in their genomic context, including
      syntenic alignments with other kinetoplastid organisms. Data within TriTrypDB can
      be interrogated utilizing a sophisticated search strategy system that enables a
      user to construct complex queries combining multiple data types. All search
      strategies are stored, allowing future access and integrated searches. 'User
      Comments' may be added to any gene page, enhancing available annotation; such
      comments become immediately searchable via the text search, and are forwarded to
      curators for incorporation into the reference annotation when appropriate.

PMID- 19843605
TI  - Modulation of the DNA-binding activity of Saccharomyces cerevisiae MSH2-MSH6
      complex by the high-mobility group protein NHP6A, in vitro.
AB  - DNA mismatch repair corrects mispaired bases and small insertions/deletions in
      DNA. In eukaryotes, the mismatch repair complex MSH2-MSH6 binds to mispairs with
      only slightly higher affinity than to fully paired DNA in vitro. Recently, the
      high-mobility group box1 protein, (HMGB1), has been shown to stimulate the
      mismatch repair reaction in vitro. In yeast, the closest homologs of HMGB1 are
      NHP6A and NHP6B. These proteins have been shown to be required for genome
      stability maintenance and mutagenesis control. In this work, we show that MSH2
      MSH6 and NHP6A modulate their binding to DNA in vitro. Binding of the yeast MSH2
      MSH6 to homoduplex regions of DNA significantly stimulates the loading of NHP6A.
      Upon binding of NHP6A to DNA, MSH2-MSH6 is excluded from binding unless a
      mismatch is present. A DNA binding-impaired MSH2-MSH6F337A significantly reduced
      the loading of NHP6A to DNA, suggesting that MSH2-MSH6 binding is a requisite for
      NHP6A loading. MSH2-MSH6 and NHP6A form a stable complex, which is responsive to
      ATP on mismatched substrates. These results suggest that MSH2-MSH6 binding to
      homoduplex regions of DNA recruits NHP6A, which then prevents further binding of
      MSH2-MSH6 to these sites unless a mismatch is present.

PMID- 19843606
TI  - Expression profiling of Drosophila mitochondrial genes via deep mRNA sequencing.
AB  - Mitochondria play an essential role in several cellular processes. Nevertheless,
      very little is known about patterns of gene expression of genes encoded by the
      mitochondrial DNA (mtDNA). In this study, we used next-generation sequencing
      (NGS) for transcription profiling of genes encoded in the mitochondrial genome of
      Drosophila melanogaster and D. pseudoobscura. The analysis of males and females
      in both species indicated that the expression pattern was conserved between the
      two species, but differed significantly between both sexes. Interestingly, mRNA
      levels were not only different among genes encoded by separate transcription
      units, but also showed significant differences among genes located in the same
      transcription unit. Hence, mRNA abundance of genes encoded by mtDNA seems to be
      heavily modulated by post-transcriptional regulation. Finally, we also identified
      several transcripts with a noncanonical structure, suggesting that processing of
      mitochondrial transcripts may be more complex than previously assumed.

PMID- 19843608
TI  - Inactive X chromosome-specific histone H3 modifications and CpG hypomethylation
      flank a chromatin boundary between an X-inactivated and an escape gene.
AB  - In mammals, the dosage compensation of sex chromosomes between males and females
      is achieved by transcriptional inactivation of one of the two X chromosomes in
      females. However, a number of genes escape X-inactivation in humans. It remains
      poorly understood how the transcriptional activity of these 'escape genes' is
      maintained despite the chromosome-wide heterochromatin formation. To address this
      question, we analyzed a putative chromatin boundary between the inactivated RBM10
      and an escape gene, UBA1/UBE1. Chromatin immunoprecipitation revealed that
      trimethylated histone H3 lysine 9 and H4 lysine 20 were enriched in the last exon
      through the proximal downstream region of RBM10, but were remarkably diminished
      at approximately 2 kb upstream of the UBA1 transcription start site. Whereas RNA
      polymerase II was not loaded onto the intergenic region, CTCF (CCCTC binding
      factor) was enriched around the boundary, where some CpG sites were
      hypomethylated specifically on inactive X. These findings suggest that local DNA
      hypomethylation and CTCF binding are involved in the formation of a chromatin
      boundary, which protects the UBA1 escape gene against the chromosome-wide
      transcriptional silencing.

PMID- 19843607
TI  - The Universal Protein Resource (UniProt) in 2010.
AB  - The primary mission of UniProt is to support biological research by maintaining a
      stable, comprehensive, fully classified, richly and accurately annotated protein
      sequence knowledgebase, with extensive cross-references and querying interfaces
      freely accessible to the scientific community. UniProt is produced by the UniProt
      Consortium which consists of groups from the European Bioinformatics Institute
      (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information
      Resource (PIR). UniProt is comprised of four major components, each optimized for
      different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt
      Reference Clusters and the UniProt Metagenomic and Environmental Sequence
      Database. UniProt is updated and distributed every 3 weeks and can be accessed
      online for searches or download at http://www.uniprot.org.

PMID- 19843609
TI  - Promoter activity of the sea urchin (Paracentrotus lividus) nucleosomal H3 and
      H2A and linker H1 {alpha}-histone genes is modulated by enhancer and chromatin
      insulator.
AB  - Core promoters and chromatin insulators are key regulatory elements that may
      direct a transcriptional enhancer to prefer a specific promoter in complex
      genetic loci. Enhancer and insulator flank the sea urchin (Paracentrotus lividus)
      alpha-histone H2A transcription unit in a tandem repeated cluster containing the
      five histone genes. This article deals with the specificity of interaction
      between the H2A enhancer-bound MBF-1 activator and histone gene promoters, and
      with the mechanism that leads the H1 transcripts to peak at about one-third of
      the value for nucleosomal H3 and H2A mRNAs. To this end, in vivo competition
      assays of enhancer and insulator functions were performed. Our evidence suggests
      that the MBF-1 transcription factor participates also in the expression of the H3
      gene and that the sns5 insulator buffers the downstream H1 promoter from the H2A
      enhancer. Altogether, these results provide a clear demonstration of the enhancer
      blocking function of a chromatin insulator in a natural gene context. In
      addition, they suggest that both the H2A enhancer and the sns5 insulator may
      account for the diverse accumulation of the linker H1 versus the core nucleosomal
      histones during early development of the sea urchin embryo.

PMID- 19843610
TI  - 5-Fluoro pyrimidines: labels to probe DNA and RNA secondary structures by 1D 19F
      NMR spectroscopy.
AB  - (19)F NMR spectroscopy has proved to be a valuable tool to monitor functionally
      important conformational transitions of nucleic acids. Here, we present a
      systematic investigation on the application of 5-fluoro pyrimidines to probe DNA
      and RNA secondary structures. Oligonucleotides with the propensity to adapt
      secondary structure equilibria were chosen as model systems and analyzed by 1D
      (19)F and (1)H NMR spectroscopy. A comparison with the unmodified analogs
      revealed that the equilibrium characteristics of the bistable DNA and RNA
      oligonucleotides were hardly affected upon fluorine substitution at C5 of
      pyrimidines. This observation was in accordance with UV spectroscopic melting
      experiments which demonstrated that single 5-fluoro substitutions in double
      helices lead to comparable thermodynamic stabilities. Thus, 5-fluoro pyrimidine
      labeling of DNA and RNA can be reliably applied for NMR based nucleic acid
      secondary structure evaluation. Furthermore, we developed a facile synthetic
      route towards 5-fluoro cytidine phosphoramidites that enables their convenient
      site-specific incorporation into oligonucleotides by solid-phase synthesis.

PMID- 19843611
TI  - Pathema: a clade-specific bioinformatics resource center for pathogen research.
AB  - Pathema (http://pathema.jcvi.org) is one of the eight Bioinformatics Resource
      Centers (BRCs) funded by the National Institute of Allergy and Infectious Disease
      (NIAID) designed to serve as a core resource for the bio-defense and infectious
      disease research community. Pathema strives to support basic research and
      accelerate scientific progress for understanding, detecting, diagnosing and
      treating an established set of six target NIAID Category A-C pathogens: Category
      A priority pathogens; Bacillus anthracis and Clostridium botulinum, and Category
      B priority pathogens; Burkholderia mallei, Burkholderia pseudomallei, Clostridium
      perfringens and Entamoeba histolytica. Each target pathogen is represented in one
      of four distinct clade-specific Pathema web resources and underlying databases
      developed to target the specific data and analysis needs of each scientific
      community. All publicly available complete genome projects of phylogenetically
      related organisms are also represented, providing a comprehensive collection of
      organisms for comparative analyses. Pathema facilitates the scientific
      exploration of genomic and related data through its integration with web-based
      analysis tools, customized to obtain, display, and compute results relevant to
      ongoing pathogen research. Pathema serves the bio-defense and infectious disease
      research community by disseminating data resulting from pathogen genome
      sequencing projects and providing access to the results of inter-genomic
      comparisons for these organisms.

PMID- 19843613
TI  - Inferred Biomolecular Interaction Server--a web server to analyze and predict
      protein interacting partners and binding sites.
AB  - IBIS is the NCBI Inferred Biomolecular Interaction Server. This server organizes,
      analyzes and predicts interaction partners and locations of binding sites in
      proteins. IBIS provides annotations for different types of binding partners
      (protein, chemical, nucleic acid and peptides), and facilitates the mapping of a
      comprehensive biomolecular interaction network for a given protein query. IBIS
      reports interactions observed in experimentally determined structural complexes
      of a given protein, and at the same time IBIS infers binding sites/interacting
      partners by inspecting protein complexes formed by homologous proteins. Similar
      binding sites are clustered together based on their sequence and structure
      conservation. To emphasize biologically relevant binding sites, several
      algorithms are used for verification in terms of evolutionary conservation,
      biological importance of binding partners, size and stability of interfaces, as
      well as evidence from the published literature. IBIS is updated regularly and is
      freely accessible via http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.html.

PMID- 19843614
TI  - Bind-n-Seq: high-throughput analysis of in vitro protein-DNA interactions using
      massively parallel sequencing.
AB  - Transcription factor-DNA interactions are some of the most important processes in
      biology because they directly control hereditary information. The targets of most
      transcription factor are unknown. In this report, we introduce Bind-n-Seq, a new
      high-throughput method for analyzing protein-DNA interactions in vitro, with
      several advantages over current methods. The procedure has three steps (i)
      binding proteins to randomized oligonucleotide DNA targets, (ii) sequencing the
      bound oligonucleotide with massively parallel technology and (iii) finding motifs
      among the sequences. De novo binding motifs determined by this method for the DNA
      binding domains of two well-characterized zinc-finger proteins were similar to
      those described previously. Furthermore, calculations of the relative affinity of
      the proteins for specific DNA sequences correlated significantly with previous
      studies (R(2 )= 0.9). These results present Bind-n-Seq as a highly rapid and
      parallel method for determining in vitro binding sites and relative affinities.

PMID- 19843615
TI  - Intestinal spirochetosis as a cause of chronic diarrhoea in patients with HIV
      infection: case report and review of the literature.
AB  - We describe a 77-year-old patient with HIV infection suffering from chronic
      diarrhoea whose colonoscopy findings showed normal appearance mucosa and tissue
      samples revealed the presence of a dense layer of spirochetes attached to the
      apical cell membrane. A literature search from 1996 to April 2009 identified 19
      additional cases of intestinal spirochetosis in patients with HIV infection.
      Analysis of cases showed that intestinal spirochetosis causes chronic diarrhoea
      in men who have sex with men (92% of patients with reported HIV infection risk
      factors) who are not severely immunosuppressed (70% with CD4 lymphocyte cells
      >200/microL). Colonoscopy examination often revealed normal appearance mucosa.
      Haematoxylin and eosin stain of biopsy samples showed the presence of
      spirochetes, but Warthin-Starry silver staining makes organisms easier to detect.
      Patients promptly responded to metronidazole or penicillin therapy. In summary,
      invasive intestinal spirochetosis should be considered in the differential
      diagnosis of patients with HIV infection and chronic diarrhoea.

PMID- 19843612
TI  - Sequence-non-specific effects of RNA interference triggers and microRNA
      regulators.
AB  - RNA reagents of diverse lengths and structures, unmodified or containing various
      chemical modifications are powerful tools of RNA interference and microRNA
      technologies. These reagents which are either delivered to cells using
      appropriate carriers or are expressed in cells from suitable vectors often cause
      unintended sequence-non-specific immune responses besides triggering intended
      sequence-specific silencing effects. This article reviews the present state of
      knowledge regarding the cellular sensors of foreign RNA, the signaling pathways
      these sensors mobilize and shows which specific features of the RNA reagents set
      the responsive systems on alert. The representative examples of toxic effects
      caused in the investigated cell lines and tissues by the RNAs of specific types
      and structures are collected and may be instructive for further studies of
      sequence-non-specific responses to foreign RNA in human cells.

PMID- 19843616
TI  - Management of hypertriglyceridaemia caused by combination antiretroviral therapy
      in HIV-infected patients: role of omega-3 polyunsaturated fatty acids at
      different dosages, compared with fibrates.

PMID- 19843617
TI  - Pitt, a novel tetratricopeptide repeat protein involved in light-dependent
      chlorophyll biosynthesis and thylakoid membrane biogenesis in Synechocystis sp.
      PCC 6803.
AB  - Biogenesis of photosynthetic pigment/protein complexes is a highly regulated
      process that requires various assisting factors. Here, we report on the molecular
      analysis of the Pitt gene (slr1644) from the cyanobacterium Synechocystis sp. PCC
      6803 (Synechocystis 6803) that encodes a membrane-bound tetratricopeptide repeat
      (TPR) protein of formerly unknown function. Targeted inactivation of Pitt
      affected photosynthetic performance and light-dependent chlorophyll synthesis.
      Yeast two-hybrid analyses and native PAGE strongly suggest a complex formation
      between Pitt and the light-dependent protochlorophyllide oxidoreductase (POR).
      Consistently, POR levels are approximately threefold reduced in the pitt
      insertion mutant. The membrane sublocalization of Pitt was found to be dependent
      on the presence of the periplasmic photosystem II (PSII) biogenesis factor PratA,
      supporting the idea that Pitt is involved in the early steps of photosynthetic
      pigment/protein complex formation.

PMID- 19843618
TI  - Available alternative incentives modulate anticipatory nucleus accumbens
      activation.
AB  - A reward or punishment can seem better or worse depending on what else might have
      happened. Little is known, however, about how neural representations of an
      anticipated incentive might be influenced by the available alternatives. We used
      event-related FMRI to investigate the activation in the nucleus accumbens (NAcc),
      while we varied the available alternative incentives in a monetary incentive
      delay task. Some task blocks included only uncertain gains and losses; others
      included the same uncertain gains and losses intermixed with certain gains and
      losses. The availability of certain gains and losses increased NAcc activation
      for uncertain losses and decreased the difference between uncertain gains and
      losses. We suggest that this pattern of activation can result from reference
      point changes across blocks, and that the worst available loss may serve as an
      important anchor for NAcc activation. These findings imply that NAcc activation
      represents anticipated incentive value relative to the current context of
      available alternative gains and losses.

PMID- 19843619
TI  - Evidence that localized variation in primate sequence divergence arises from an
      influence of nucleosome placement on DNA repair.
AB  - Understanding the origins of localized substitution rate heterogeneity has
      important implications for identifying functional genomic sequences. Outside of
      gene regions, the origins of rate heterogeneity remain unclear. Experimental
      studies establish that chromatin compaction affects rates of both DNA lesion
      formation and repair. A functional association between chromatin status and 5
      methyl-cytosine also exists. These suggest that both the total rate and the type
      of substitution will be affected by chromatin status. Regular positioning of
      nucleosomes, the building block of chromatin, further predicts that substitution
      rate and type should vary spatially in an oscillating manner. We addressed
      chromatin's influence on substitution rate and type in primates. Matched numbers
      of sites were sampled from Dnase I hypersensitive (DHS) and closed chromatin
      control flank (Flank). Likelihood ratio tests revealed significant excesses of
      total and of transition substitutions in Flank compared with matched DHS for both
      intergenic and intronic samples. An additional excess of CpG transitions was
      evident for the intergenic, but not intronic, regions. Fluctuation in
      substitution rate along approximately 1,800 primate promoters was measured using
      phylogenetic footprinting. Significant positive correlations were evident between
      the substitution rate and a nucleosome score from resting human T-cells, with up
      to approximately 50% of the variance in substitution rate accounted for. Using
      signal processing techniques, a dominant oscillation at approximately 200 bp was
      evident in both the substitution rate and the nucleosome score. Our results
      support a role for differential DNA repair rates between open and closed
      chromatin in the spatial distribution of rate heterogeneity.

PMID- 19843620
TI  - Evaluation of quality-of-life measures for use in palliative care: a systematic
      review.
AB  - PURPOSE: In this literature review we evaluated the feasibility and clinimetric
      quality of quality-of-life (QoL) measurement instruments suitable for use in
      palliative care. METHODS: We conducted a systematic literature review to identify
      instruments measuring (at least one domain of) QoL. We selected articles that
      present data on patients receiving palliative care and at least one measurement
      property. A checklist was used to describe the characteristics of the
      instruments, and a widely accepted rating list was used to evaluate the
      clinimetric aspects. RESULTS: 29 instruments were identified and evaluated, most
      of which were targeted at palliative patients in general. None of the instruments
      demonstrated satisfactory results for all measurement properties. Fourteen
      instruments received positive ratings for construct validity. Thirteen
      instruments were tested for reliability, but only two were tested adequately and
      had positive results (ICC>0.70). Responsiveness was not tested adequately for any
      of the instruments. Very few of the studies provided information on the
      interpretation of the scores. Overall, the MQOL, followed by the QUAL-E and the
      QODD, received the best ratings for their measurement properties. CONCLUSIONS:
      Many measurement instruments were identified, but most had not yet been
      adequately evaluated. The evaluation of existing instruments with good content
      validity should have priority over the development of new instruments.

PMID- 19843621
TI  - Creating social work competencies for practice in hospice palliative care.
AB  - Social workers play an important role in the delivery of Hospice Palliative Care
      in many diverse settings. The profession brings a unique perspective to end-of
      life care that reflects and supports the holistic philosophy of Hospice
      Palliative Care. Despite the prominent and longstanding position of social work
      in this area, the role and functions of social workers had not been clearly
      defined. A Canadian task group of social work practitioners and educators
      utilized a modified Delphi process to consult front line clinicians nationally,
      and thereby achieved consensus regarding the identification and description of
      eleven core competencies in Hospice Palliative Care. These competencies are
      relevant for social workers at different experience levels across care settings.
      They can be used to inform social work practice, as well as professional
      development and educational curricula in this area.

PMID- 19843622
TI  - Small, smaller, smallest. Steps towards bloodless neonatal and infant
      cardiopulmonary bypass.
AB  - In open heart surgery in neonates and small children, the cardiopulmonary bypass
      circuit surface and the priming volume are relatively large in relation to
      patient size and blood volume. Therefore, the use of allogeneic blood is
      inevitable to maintain the optimal hematocrit level during bypass. To avoid the
      deleterious effects of blood transfusion, as well as to reduce the contact
      surface of blood with artificial materials, we stepwise reduced the bypass
      circuit size. Use of the commercially available minimized elements and an
      adjusted set-up of the system allowed us to reduce usage of allogeneic blood in
      the prime and during the bypass. However, other supplemental measures are needed
      to obtain asanguineous cardiopulmonary bypass for neonatal and infant patients.

PMID- 19843623
TI  - Effect of preoperative atorvastatin therapy on paraoxonase activity and oxidative
      stress after coronary artery bypass grafting.
AB  - The aim of this study was to examine the influence of preoperative atorvastatin
      therapy on oxidative stress in coronary artery bypass grafting (CABG) patients.
      Forty patients who underwent elective CABG were enrolled into the study. Of these
      patients, 20 received atorvastatin (Group I) for 15 days prior to surgery and 20
      patients did not use any antihyperlipidemic agents preoperatively (Group II).
      Serum paraoxonase 1 (PON1) and arylesterase activities, and total antioxidant
      status (TAS) and total oxidant status (TOS) were measured before surgery and at
      1, 6 and 24 hours after the operation. Paraoxonase 1 and arylesterase activities
      (p<0.001) and TAS levels (p<0.001 for 1(st) hour and p<0.05 for 6(th) hour) in
      Group II were significantly reduced at the 1( st) and 6(th) hours after the
      operation, whereas the activities of the enzymes (p<0.01) and TAS levels (p<0.05)
      were significantly reduced only at the 1(st) hour after the operation in Group I.
      The total oxidant status of both groups was significantly increased at the 1( st)
      hour after operation (p<0.05 for Group I and p<0.01 for Group II). In conclusion,
      15 days of preoperative atorvastatin therapy does not significantly change either
      the serum PON1 activity or the oxidative stress after CABG.

PMID- 19843624
TI  - Four corner arthrodesis limited to the centre using a scaphoid one piece graft
      and a dorsal circular plate.
AB  - We present 20 patients, who had a four corner arthrodesis, from July 2006 to
      March 2008, using a dorsal circular plate, to treat scaphoid nonunion and
      scapholunate dissociation with advanced collapse (SNAC, SLAC). The surgical
      technique was a fusion restricted to the central area filled with one piece of
      cancellous bone graft taken from the excised scaphoid. Wrist motion, grip
      strength, and Disabilities of Arm Shoulder and Hand (DASH) score improved after
      surgery at a mean follow-up of 20.2 months. Fusion occurred in 19/20 patients.
      Two patients (10%) had persistent pain. The rest had a good clinical result. We
      found that four-corner fusion using a dorsal circular plate using the specific
      technical modifications was successful.

PMID- 19843625
TI  - Structural characteristics of the subscapularis muscle in children with medial
      rotation contracture of the shoulder after obstetric brachial plexus injury.
AB  - The aim of this study was to obtain a better understanding of the cause of the
      medial rotation contracture of the shoulder after obstetric brachial plexus
      lesions by studying the morphology of the shortened subscapularis muscle. Muscle
      biopsy specimens were harvested from 13 children with obstetric brachial plexus
      palsy who underwent corrective surgery for the rotation contracture. The majority
      of the subscapularis muscle biopsy samples had an essentially normal morphology
      and showed a predominance of type I myosin heavy chain isoform, while one biopsy
      showed signs of marked fibrosis and a predominance of type II myosin heavy chain
      isoform. The findings support the assumption that shortening of the subscapularis
      is caused primarily by the nerve injury, which weakens the antagonistic lateral
      rotators, but that direct injury to the muscle might be a contributory factor.

PMID- 19843626
TI  - Simultaneous pedicled flaps for coverage of complex blast injuries to the forearm
      and hand (with supplemental external fixation to the iliac crest for
      immobilization).
AB  - The technique of two simultaneous pedicled flaps to a single extremity has
      recently proven useful in the care of war-injured military personnel. We present
      two cases of combat-injured Marines who underwent upper extremity reconstruction
      using simultaneous pedicled flaps. These cases illustrate a simple and successful
      alternative to free tissue transfer in providing coverage to complex soft tissue
      defects of the hand and forearm. Good outcomes were obtained in circumstances
      where free tissue transfer was not indicated.

PMID- 19843627
TI  - Upper limb functional restoration in old and complete brachial plexus paralysis.
AB  - Nineteen patients with longstanding and permanent brachial plexus injuries
      underwent a three-staged surgical reconstruction. First, a sural nerve was
      grafted from the contralateral intact medial pectoral nerve to the paralyzed arm.
      One year later, a free gracilis muscle was transferred and neurotized by the
      grafted sural nerve. This procedure results in reanimation of elbow flexion.
      Finally, the biceps tendon was transferred to the finger flexors using a fascia
      bundle of tensor fascia lata muscle. Two of the gracilis muscle free transfers
      failed. In the remaining 17 patients, the overall result was evaluated as
      satisfactory in 11 patients and good in 6.

PMID- 19843628
TI  - Reduced attentional blink for alcohol-related stimuli in heavy social drinkers.
AB  - Researchers have used various paradigms to show that attentional biases for
      substance-related stimuli are an important feature of addictive behaviours.
      However, it is not clear whether these attentional biases occur at the level of
      encoding or at later post-attentive processing stages. We examined attentional
      bias at the level of encoding with the attentional blink paradigm in a sample of
      non-clinical heavy and light-drinking students. Our results show a diminished
      attentional blink effect for alcohol-related words compared with soft drink
      related words among heavy drinkers. The attentional blink was equally strong for
      alcohol-related and soft drink-related words among light drinkers. This suggests
      that alcohol-related information is processed relatively more efficiently in the
      former group. Even though these results are promising, our study shows that the
      internal consistency of the attentional blink can be improved.

PMID- 19843629
TI  - The distribution of ''sense of coherence'' among Swedish adults: a quantitative
      cross-sectional population study.
AB  - BACKGROUND: Antonovsky's concept of ''sense of coherence'' (SOC) has been shown
      to be related to health. The aim of this study was to describe the distribution
      of SOC scores and their components in an adult Swedish population aged 20-80
      years. METHODS: A random sample of 910 individuals from Jonkoping, Sweden, aged
      20, 30, 40, 50, 60, 70 and 80 years, of which 589 agreed to participate in an
      oral health examination. The participants answered Antonovsky's 13-item version
      of ''the life orientation questionnaire scale''. The response to the items and
      the distribution of the three components of comprehensibility, manageability and
      meaningfulness were analyzed for different age groups and genders using mean
      values and standard deviations, Student's t-test and ANOVA. RESULTS: A total of
      526 individuals, 263 men and 263 women, answered all 13 questions and constituted
      the final material for the study (response rate 89%). The individual SOC score
      increased with age. The 20 year olds had a statistically significantly lower SOC
      score compared with the other age groups and 55% of them had a low SOC (< or = 66
      points) compared with 17% of the 80 year olds. Men in the 60 and 70 year age
      groups had a statistically significantly higher SOC score compared with women of
      the same age. CONCLUSIONS: The individual distribution of SOC varied with age and
      gender. Twenty year olds had a significantly lower SOC score compared with
      elderly age groups. Elderly men had a statistically significantly higher SOC
      score compared with women of the same age.

PMID- 19843630
TI  - Aortic arginine transport is attenuated, through post-translational modulation of
      CAT-1 by PKCalpha, in old male rats.
AB  - Experimental models using rats suggest that decreased endothelial nitric oxide
      synthase (eNOS) activity in old males promotes renal atherosclerosis, whereas
      females are protected. We aimed to explore whether aging alters aortic arginine
      uptake by CAT-1, the selective arginine supplier to eNOS in rats. Arginine uptake
      by freshly harvested aortic rings from young males (9 weeks) was significantly
      higher than in young females. Old males (18 months) exhibited a significant
      decrease in arginine transport compared to young males, whereas no differences
      were observed between old and young females. Cationic amino acid transporter-1
      (CAT-1) abundance remained unchanged in all experimental groups. The abundance of
      protein kinase C alpha (PKCalpha), a CAT-1 inhibitor, was significantly augmented
      in old versus young males while no differences were detected between old and
      young females. Phosphorylated PKCalpha was significantly increased in old rats of
      both sexes. alphaTocopherol, a PKC inhibitor, produced a significant increase in
      arginine transport in old males only. In conclusion, aortic arginine transport by
      CAT-1 is attenuated in old male rats through upregulation of PKCalpha. In old
      females, aortic arginine transport is protected from the effects of PKCalpha by
      an unknown mechanism.

PMID- 19843631
TI  - UNC45A confers resistance to histone deacetylase inhibitors and retinoic acid.
AB  - To identify potential biomarkers of therapy response, we have previously done a
      large-scale gain-of-function genetic screen to identify genes whose expression
      confers resistance to histone deacetylase inhibitors (HDACI). This genetic screen
      identified two genes with a role in retinoic acid signaling, suggesting that
      HDACIs target retinoic acid signaling as part of their anticancer effect. We
      study here a third gene identified in this genetic screen, UNC45A, and assess its
      role in retinoic acid signaling and responses to HDACIs using cell-based
      proliferation and differentiation assays and transcriptional reporter gene
      assays. The vertebrate Unc45 genes are known for their roles in muscle
      development and the assembly and cochaperoning of the muscle motor protein
      myosin. Here, we report that human UNC45A (GCUNC45) can render transformed cells
      resistant to treatment with HDACIs. We show that UNC45A also inhibits signaling
      through the retinoic acid receptor alpha. Expression of UNC45A inhibits retinoic
      acid-induced proliferation arrest and differentiation of human neuroblastoma
      cells and inhibits the induction of endogenous retinoic acid receptor target
      genes. These data establish an unexpected role for UNC45A in causing resistance
      to both HDACI drugs and retinoic acid. Moreover, our data lend further support to
      the notion that HDACIs exert their anticancer effect, at least in part, through
      an effect on retinoic acid signaling.

PMID- 19843633
TI  - The human ADFP gene is a direct liver-X-receptor (LXR) target gene and
      differentially regulated by synthetic LXR ligands.
AB  - Expression of adipocyte differentiation-related protein (ADFP), residing on the
      surface of lipid droplets, correlates to hepatic fat storage. In the context of
      consequences and treatment of metabolic disorders, including hepatic steatosis,
      it is imperative to gain knowledge about the regulation of the human ADFP gene.
      The nuclear receptor liver-X-receptor (LXR) is a key regulator of hepatic fatty
      acid biosynthesis and cholesterol homeostasis as well as a potential drug target.
      Here, we report that two synthetic LXR ligands differently regulate human ADFP
      expression. The partial LXR agonist 3-[3-[[[2-chloro-3
      (trifluoromethyl)phenyl]methyl](2,2- diphenylethyl)amino]propoxy]benzeneacetic
      acid hydrochloride (GW3965) significantly induces ADFP expression in human
      primary hepatocytes, whereas the full agonist N-(2,2,2-trifluoroethyl)-N-[4
      [2,2,2-trifluoro-1-hydroxy-1(trifluoromethyl)ethyl]phenyl] benzenesulfonamide
      (T0901317) does not. Bioinformatics analysis revealed several potential LXR
      response elements (LXREs) in the human ADFP gene. By using chromatin
      immunoprecipitation and luciferase reporter assays, we show that LXR, upon
      stimulation with GW3965, directly regulates human ADFP transcription by binding
      to LXREs located in the 3'-untranslated and the 5'-flanking regions. The ligand
      stimulated LXR recruitment was associated with recruitment of RNA polymerase II
      and the coactivators cAMP response element-binding protein-binding protein/p300
      to the promoter region demonstrating that the identified LXREs are functional and
      able to induce transcription. Moreover, our results show that sequence identity
      of the hexamer repeats in DR4 elements is not sufficient to determine whether the
      element binds LXR or not. The partial agonist GW3965 specifically regulates ADFP
      gene transcription, and our data prove that the two synthetic LXR agonists,
      commonly used in experimental research, can differentially regulate gene
      expression. This has implications for pharmaceutical targeting of LXR.

PMID- 19843632
TI  - Repeated treatment with subtoxic doses of TRAIL induces resistance to apoptosis
      through its death receptors in MDA-MB-231 breast cancer cells.
AB  - Recombinant human tumor necrosis factor-related apoptosis-inducing ligand
      (rhTRAIL) is being evaluated clinically in treating various malignancies.
      Previous studies have shown that repeated application of high doses of rhTRAIL
      results in a subpopulation of parental cells that is unresponsive to the death
      ligand. However, it is not clear whether TRAIL-sensitive cancer cells could
      acquire resistance to TRAIL treatment. Here, we found that MDA-MB-231 breast
      cancer cells, which are highly sensitive to TRAIL-induced apoptosis, became
      resistant to TRAIL killing after a prolonged exposure to subtoxic doses of
      rhTRAIL. The resulting TRAIL-resistant cells were cross-resistant to antibodies
      against its death receptors (DR4 and DR5); however, they retained sensitivity to
      several clinically relevant chemotherapies. Surface expression of DR4 and DR5 was
      significantly reduced in the selected cells, resulting in failure in death
      inducing signaling complex formation and caspase activation. In addition, real
      time PCR analysis revealed an upregulation in multiple apoptosis-regulator genes,
      including c-FLIP, Stat5a, and Stat5b. Inhibition of Janus-activated kinase, an
      upstream activator of signal transducer and activator of transcription 5 (Stat5),
      or knockdown of Stat5 itself partially restored cellular sensitivity to TRAIL
      induced apoptosis, suggesting that Stat5 signaling is also involved in the
      development of TRAIL resistance. Furthermore, we showed that acquired TRAIL
      resistance was effectively eliminated by combination with etoposide, doxorubicin,
      or paclitaxel. These results suggest that tumor cells could acquire resistance to
      TRAIL therapy especially when they are repeatedly exposed to low levels of the
      death ligand, highlighting the necessity of combination with therapies that
      target the resistance mechanisms.

PMID- 19843634
TI  - Inhibitors of the mitochondrial citrate transport protein: validation of the role
      of substrate binding residues and discovery of the first purely competitive
      inhibitor.
AB  - The mitochondrial citrate transport protein (CTP) is critical to energy
      metabolism in eukaryotic cells. We demonstrate that 1,2,3-benzenetricarboxylate
      (BTC), the classic and defining inhibitor of the mitochondrial CTP, is a mixed
      inhibitor of the reconstituted Cys-less CTP, with a strong competitive component
      [i.e., a competitive inhibition constant (K(ic)) of 0.12 +/- 0.02 mM and an
      uncompetitive inhibition constant (K(iu)) of 3.04 +/- 0.74 mM]. Based on docking
      calculations, a model for BTC binding has been developed. We then determined the
      K(ic) values for each of the eight substrate binding site cysteine substitution
      mutants and observed increases of 62- to 261-fold relative to the Cys-less
      control, thereby substantiating the importance of each of these residues in BTC
      binding. It is noteworthy that we observed parallel increases in the K(m) for
      citrate transport with each of these binding site mutants, thereby confirming
      that with these CTP variants, K(m) approximates the K(d) (for citrate) and is
      therefore a measure of substrate affinity. To further substantiate the importance
      of these binding site residues, in silico screening of a database of commercially
      available compounds has led to discovery of the first purely competitive
      inhibitor of the CTP. Docking calculations indicate that this inhibitor spans and
      binds to both substrate sites simultaneously. Finally, we propose a kinetic model
      for citrate transport in which the citrate molecule sequentially binds to the
      external and internal binding sites (per CTP monomer) before transport.

PMID- 19843635
TI  - Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of
      primordial follicles.
AB  - To maintain the length of reproductive life in a woman, it is essential that most
      of her ovarian primordial follicles are maintained in a quiescent state to
      provide a continuous supply of oocytes. However, our understanding of the
      molecular mechanisms that control the quiescence and activation of primordial
      follicles is still in its infancy. In this study, we provide some genetic
      evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2),
      which negatively regulates mammalian target of rapamycin complex 1 (mTORC1),
      functions in oocytes to maintain the dormancy of primordial follicles. In mutant
      mice lacking the Tsc2 gene in oocytes, the pool of primordial follicles is
      activated prematurely due to elevated mTORC1 activity in oocytes. This results in
      depletion of follicles in early adulthood, causing premature ovarian failure
      (POF). Our results suggest that the Tsc1-Tsc2 complex mediated suppression of
      mTORC1 activity is indispensable for maintenance of the dormancy of primordial
      follicles, thus preserving the follicular pool, and that mTORC1 activity in
      oocytes promotes follicular activation. Our results also indicate that
      deregulation of Tsc/mTOR signaling in oocytes may cause pathological conditions
      of the ovary such as infertility and POF.

PMID- 19843636
TI  - Medicine prices in urban Mozambique: a public health and economic study of
      pharmaceutical markets and price determinants in low-income settings.
AB  - It has been suggested that medicines are unaffordable in low-income countries and
      that world manufacturing and trade policies are responsible for high prices. This
      research investigates medicine prices in urban Mozambique with the objective of
      understanding how prices are formed and with what public health implications. The
      study adopts an economic framework and uses a combination of quantitative and
      qualitative methods to analyse local pharmaceutical prices and markets. The
      research findings suggest that: (a) local mark-ups are responsible for up to two
      thirds of drugs' final prices in private pharmacies; (b) statutory profit and
      cost ceilings are applied unevenly, due to lack of government control and
      collusion among suppliers; and (c) the local market appears to respond
      effectively to the urban population's diverse needs through its low-cost and high
      cost segments, although uncertainty around the quality of generics may be
      inducing consumers to purchase less affordable drugs. We conclude that local
      markets play a larger than expected role in the determination of prices in
      Mozambique, and that more research is needed to address the complex issue of
      affordability of medicines in low-income countries. We also argue that price
      controls may not be the most effective way to influence access to medicines in
      low-income countries, and managing demand and supply towards cheaper effective
      drugs appears a more suitable policy option.

PMID- 19843637
TI  - Community health insurance in Gudalur, India, increases access to hospital care.
AB  - BACKGROUND: To reduce the burden of out-of-pocket payments on households in
      India, the government has introduced community health insurance (CHI) as part of
      its National Rural Health Mission. Indian CHI schemes have been shown to provide
      financial protection and have the potential to improve quality of care, but do
      not seem to improve access. This study examines this dimension of CHI performance
      and explores conditions under which a CHI scheme can improve access to hospital
      care for the poor. METHODS: We conducted a panel survey at the ACCORD-AMS-ASHWINI
      (AAA) CHI scheme in India. The AAA CHI scheme protects the poorest sections of
      society against hospitalization expenses. 297 insured and 248 matched uninsured
      households were observed by village volunteers on a weekly basis for 12 months.
      Any patient presenting with a 'major ailment' in these households was interviewed
      using a structured questionnaire. Outcomes measured were utilization of hospital
      services, cost of treatment and quality of treatment received. RESULTS: The two
      cohorts were similar regarding demographic, social and economic parameters. More
      insured than uninsured households expressed trust in the CHI scheme organizers.
      Both groups had similar levels of minor ailments, but the insured had higher
      incidence of chronic and major ailments. Insured patients had a hospital
      admission rate 2.2 times higher than uninsured patients, independent of
      confounding factors. This higher rate among the insured was also found in
      children and those with pre-existing conditions. Vulnerable sections of the
      insured population-children, pregnant women, the poorest-had the highest
      admission rates. Most admissions, in both cohorts, took place in the ASHWINI
      hospital. Credible and trustworthy organizers, effective providers, low co
      payments, and low indirect costs contributed to this result. CONCLUSIONS: A well
      designed CHI scheme has the potential to improve access to hospital care, even
      for vulnerable sections of the community-the poorest, individuals with pre
      existing conditions like diabetes and hypertension, and pregnant women.

PMID- 19843638
TI  - Where did all the GPs go? Increasing supply and geographical equity in England
      and Scotland.
AB  - OBJECTIVES: To examine the effect on geographical equity of increases in the
      total supply of general practitioners (GPs) and the ending of entry restrictions
      in 2002 and to explore the factors associated with the distribution of GPs across
      England. METHODS: Calculation of Gini coefficients to measure geographical equity
      in GPs per 100,000 population in England and Scotland. Multiple regression of GPs
      per capita and change in GPs per capita on demographics, morbidity, deprivation
      and measures of amenity in English Primary Care Trusts (PCTs). RESULTS: Equity in
      England rose between 1974 and 1994 but then decreased, and in 2006 it was below
      the 1974 level. After 2002, England had a greater percentage increase in GP
      supply than Scotland and a smaller increase in inequity. The level of GP per
      capita supply in 2006 was positively correlated with morbidity and PCT amenity,
      and negatively correlated with unemployment and poor air quality. The increase in
      per capita supply between 2002 and 2006 was not significantly associated with
      morbidity, deprivation or amenities. CONCLUSIONS: Reducing geographical inequity
      in the provision of GPs requires targeted area level policies.

PMID- 19843639
TI  - Do telephones overcome geographical barriers to general practice out-of-hours
      services? Mixed-methods study of parents with young children.
AB  - OBJECTIVE: To examine if telephones overcome geographical barriers to accessing
      primary care out-of-hours by parents of young children. METHODS: Mixed methods
      including quantitative analysis of 5697 calls about children aged 0-4 years, 30
      hours of observation at primary care centres, eight interviews with parents and a
      review of 80 telephone call recordings. RESULTS: Call rates for children (0-4
      years) decreased with increasing distance: the 20% of people who lived furthest
      from a primary care centre made fewer calls, 570 per 1000 patients/year (95% CI
      558 to 582) than the 20% living closest, 652 (95% CI 644 to 661). Overall, call
      rates decreased with increasing rurality. Qualitative analysis suggested that
      this geographical variation was linked to familiarity with the system (notably
      previous contact with health services) and the availability of services,
      legitimacy of demand (particularly for children) and negotiation about mode of
      care. CONCLUSIONS: People already disadvantaged by their distance from facilities
      or socioeconomic circumstances may continue to be at a disadvantage when services
      are provided by telephone.

PMID- 19843640
TI  - Abl interactor 1 regulates Src-Id1-matrix metalloproteinase 9 axis and is
      required for invadopodia formation, extracellular matrix degradation and tumor
      growth of human breast cancer cells.
AB  - Abl interactor 1 (Abi1) is a key regulator of actin
      polymerization/depolymerization. The involvement of Abi1 in the development of
      abnormal cytoskeletal functions of cancer cells has recently been reported. It
      remains unclear, however, how Abi1 exerts its effects in tumor cells and whether
      it contributes to tumor progression in vivo. We report here a novel function for
      Abi1 in the regulation of invadopodia formation and Src-inhibitor of
      differentiation protein 1 (Id1)-matrix metalloproteinase (MMP)-9 pathway in MDA
      MB-231 human breast cancer cells. Abi1 is found in the invadopodia of MDA-MB-231
      cells. Epigenetic silencing of the Abi1 gene by short hairpin RNA in MDA-MB-231
      cells impaired the formation of invadopodia and resulted in downregulation of the
      Src activation and Id1/MMP-9 expression. The decreased invadopodia formation and
      MMP-9 expression correlate with a reduction in the ability of these cells to
      degrade extracellular matrix. Remarkably, the knockdown of Abi1 expression
      inhibited tumor cell proliferation and migration in vitro and slowed tumor growth
      in vivo. Taken together, these results indicate that the Abi1 signaling plays a
      critical role in breast cancer progression and suggest that this pathway may
      serve as a therapeutic target for the treatment of human breast cancer.

PMID- 19843641
TI  - A novel oncolytic adenovirus selectively silences the expression of tumor
      associated STAT3 and exhibits potent antitumoral activity.
AB  - Tumor cells acquire the ability to proliferate uncontrollably, resist apoptosis,
      sustain angiogenesis and evade immune surveillance. Signal transducer and
      activator of transcription (STAT) 3 regulates all of these processes in a
      surprisingly large number of human cancers. Consequently, the STAT3 protein is
      emerging as an ideal target for cancer therapy. This paper reports the generation
      of an oncolytic adenovirus (M4), which selectively blocks STAT3 signaling in
      tumor cells as a novel therapeutic strategy. M4 selectively replicated in tumor
      cells and expressed high levels of antisense STAT3 complementary DNA during the
      late phase of the viral infection in a replication-dependent manner. The viral
      progeny yield of M4 in tumor cells was much higher than that of the parent
      adenoviral mutants, Ad5/dE1A. M4 effectively silenced STAT3 and its target genes
      in tumor cells while sparing normal cells and exhibited potent antitumoral
      efficacy in vitro and in vivo. Systemic administration of M4 significantly
      inhibited tumor growth in an orthotopic gastric carcinoma mouse model, eliminated
      abdominal cavity metastases and prolonged survival time. In summary, M4 has low
      toxicity and great potential as a therapeutic agent for different types of
      cancers.

PMID- 19843643
TI  - miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in
      hepatocellular carcinoma.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs that, in general,
      negatively regulate gene expression. They have been identified in various tumor
      types, showing that different sets of miRNAs are usually deregulated in different
      cancers. Some miRNA genes harboring CpG islands undergo methylation-mediated
      silencing, a characteristic of many tumor suppressor genes. To identify such
      miRNAs in hepatocellular carcinoma (HCC), we first examined the methylation
      status of 43 loci containing CpG islands around 39 mature miRNA genes in a panel
      of HCC cell lines and non-cancerous liver tissues as controls. Among 11 miRNA
      genes frequently methylated in HCC cell lines but not in non-cancerous liver
      tissues, three miRNA genes, i.e. miR-124, miR-203 and miR-375, were selected as
      silenced miRNAs through CpG-island methylation by comparing methylation and
      expression status and evaluating restored expression after treatment with 5-aza
      2'-deoxycytidine. In primary tumors of HCC with paired non-tumorous liver
      tissues, only miR-124 and miR-203 showed frequent tumor-specific methylation, and
      their expression status was inversely correlated with methylation status. Ectopic
      expression of miR-124 or miR-203 in HCC cells lacking their expression inhibited
      cell growth, with direct downregulation of possible targets, cyclin-dependent
      kinase 6 (CDK6), vimentin (VIM), SET and MYND domain containing 3 (SMYD3) and IQ
      motif containing GTPase activating protein 1 (IQGAP1) or ATP-binding cassette,
      subfamily E, member 1 (ABCE1), respectively. Our results suggest that miR-124 and
      miR-203 are novel tumor-suppressive miRNAs for HCC epigenetically silenced and
      activating multiple targets during hepatocarcinogenesis.

PMID- 19843642
TI  - Cucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in
      vivo tumor formation ability of nasopharyngeal carcinoma cells.
AB  - Nasopharyngeal carcinoma (NPC) is an Asian-prevalent head and neck cancer with
      high invasiveness. Although several important risk factors for NPC development
      have been identified, there is currently no preventive strategy for NPC, even in
      endemic regions. Signal transducer and activator of transcription 3 (STAT3) has
      been implicated in NPC carcinogenesis, which may serve as a potential target for
      cancer prevention. Here, we examined the chemopreventive potential of
      Cucurbitacin I, a natural-occurring selective inhibitor of JAK/STAT3, in NPC
      models. We hypothesized that Cucurbitacin I would prevent NPC invasion and tumor
      formation. Our data demonstrated that brief exposure of NPC cells to Cucurbitacin
      I was sufficient to significantly reduce the in vitro clonogenicity and in vivo
      tumorigenicity of NPC cells. The chemopreventive potential of Cucurbitacin I was
      further demonstrated by pre-dosing of the animals with Cucurbitacin I prior to
      tumor inoculation, which was found to be able to suppress tumor growth up to 7
      days post-inoculation. The anti-proliferation activity of Cucurbitacin I was
      accompanied by downregulation of phospho-STAT3 and STAT3 target gene expression
      (e.g. cyclin D1 and Mcl-1). Cucurbitacin I also reduced the invasiveness of
      invasive NPC cell lines with elevated STAT3 activation. Furthermore, our data
      demonstrated for the first time that Cucurbitacin I harbored potent anoikis
      sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell
      death) against human cancer. Taken together, our results suggested that
      Cucurbitacin I may be a potent chemopreventive agent for NPC with anti-invasion
      and anoikis-sensitizing activities.

PMID- 19843644
TI  - Loss of imprinting of the insulin-like growth factor II (IGF2) gene in esophageal
      normal and adenocarcinoma tissues.
AB  - To evaluate loss of imprinting (LOI) and expression of the IGF2 gene in matched
      esophageal normal and adenocarcinoma tissues, we studied a prospective cohort of
      77 patients who underwent esophageal resection between 1998 and 2003. IGF2
      imprinting status was determined by reverse transcription-polymerase chain
      reaction (PCR) following ApaI digestion, and quantitative PCR was used to
      evaluate IGF2 expression, which was correlated with clinicopathologic findings,
      disease-free and overall survival. In total, 32% (14/44) of informative tissues
      showed loss of IGF2 imprinting, with a strong correlation between the tumor and
      normal esophageal epithelia (Kappa = 0.89, P < 0.01). Normal epithelia with LOI
      had increased expression of IGF2 [median: 2.91, 95% confidence interval (CI):
      0.93-5.06] compared with imprinted normal epithelia (median: 1.13, 95% CI: 0.85
      1.39) (P = 0.03). In contrast, tumors with LOI had significantly reduced IGF2
      expression (median: 1.87, 95% CI: 0.53-5.21) compared with normally imprinted
      tumors (median: 6.79, 95% CI: 3.39-15.89) (P = 0.016). Patients below the age of
      65 years with normally imprinted tumors had significantly reduced 5 year disease
      free survival (DFS) (24%) compared with patients whose tumors had LOI for IGF2
      (55%) (P = 0.03). Cox regression analysis showed that IGF2 overexpression was
      associated with significantly reduced disease-free survival (P = 0.04). We
      conclude that in a subgroup of younger patients, loss of IGF2 imprinting was
      associated with improved outcome following esophageal resection. Expression of
      IGF2 in esophageal adenocarcinoma and normal esophageal epithelia depended on
      imprinting status and tissue type, suggesting novel molecular regulatory
      mechanisms in esophageal tumorigenesis.

PMID- 19843645
TI  - Lung cancer susceptibility among atomic bomb survivors in relation to CA repeat
      number polymorphism of epidermal growth factor receptor gene and radiation dose.
AB  - Lung cancer is a leading cause of cancer death worldwide. Prevention could be
      improved by identifying susceptible individuals as well as improving
      understanding of interactions between genes and etiological environmental agents,
      including radiation exposure. The epidermal growth factor receptor (EGFR)
      signaling pathway, regulating cellular radiation sensitivity, is an oncogenic
      cascade involved in lung cancer, especially adenocarcinoma. The cytosine adenine
      (CA) repeat number polymorphism in the first intron of EGFR has been shown to be
      inversely correlated with EGFR production. It is hypothesized that CA repeat
      number may modulate individual susceptibility to lung cancer. Thus, we carried
      out a case-cohort study within the Japanese atomic bomb (A-bomb) survivor cohort
      to evaluate a possible association of CA repeat polymorphism with lung cancer
      risk in radiation-exposed or negligibly exposed (<5 mGy) A-bomb survivors. First,
      by dividing study subjects into Short and Long genotypes, defined as the summed
      CA repeat number of two alleles < or = 37 and > or = 38, respectively, we found
      that the Short genotype was significantly associated with an increased risk of
      lung cancer, specifically adenocarcinoma, among negligibly exposed subjects.
      Next, we found that prior radiation exposure significantly enhanced lung cancer
      risk of survivors with the Long genotype, whereas the risk for the Short genotype
      did not show any significant increase with radiation dose, resulting in
      indistinguishable risks between these genotypes at a high radiation dose. Our
      findings imply that the EGFR pathway plays a crucial role in assessing individual
      susceptibility to lung adenocarcinoma in relation to radiation exposure.

PMID- 19843646
TI  - Potentially inappropriate medication use in older adults with mild cognitive
      impairment.
AB  - BACKGROUND: Patients with mild cognitive impairment (MCI) may be especially
      vulnerable to the side effects of potentially inappropriate medications (PIMs),
      especially those that impair cognition. METHODS: We conducted a cross-sectional
      study to determine the prevalence of PIM use among 689 patients with MCI. We used
      the 2003 Beers Criteria for cognitive impairment to identify PIMs. We then
      determined if certain patients were more likely to use PIMs. RESULTS: There were
      143 (20.8%) patients with MCI taking a PIM: 108 (15.7%) patients were taking one
      PIM and 35 (5.1%) patients were taking two or more PIMs. The most common PIMs
      were anticholinergics (35.7%) and benzodiazepines (31.5%). Patients were more
      likely to be taking PIMs if they were women and were taking a greater number of
      medications and less likely if they had a history of myocardial infarction.
      CONCLUSIONS: Patients with MCI are frequently taking PIMs that may negatively
      affect cognition. Future research is needed to assess whether cognitive
      impairment symptoms are improved if PIM use is reduced.

PMID- 19843647
TI  - The natural history of Charcot-Marie-Tooth type 1A in adults: a 5-year follow-up
      study.
AB  - Charcot-Marie-Tooth type 1A is the most prevalent hereditary demyelinating
      polyneuropathy. The aim of this study was to investigate the natural history of
      the disease in adults during a 5-year follow-up and to compare the changes over
      time with those found in normal ageing. In a cohort of 46 adult Charcot-Marie
      Tooth type 1A patients, impairments and physical disability were scored at
      baseline and at 1, 3 and 5 years. Standardized nerve conduction studies and
      electromyography were performed at baseline and at 5 years. Twenty-six healthy
      age- and sex-matched controls were evaluated at baseline and at 5 years. Forty
      four of 46 Charcot-Marie-Tooth type 1A patients (range 17-69 years) and 26
      controls (range 25-65 years) completed the 5-year follow-up. The decrease in
      muscle strength and in compound muscle action potential amplitudes was similar
      for patients and controls alike. However, in contrast to the control group,
      physical disability increased over time in the patient group. In patients, muscle
      strength and physical disability after 5 years were closely related to these
      parameters at baseline. None of the other assessed baseline characteristics, i.e.
      age, gender, compound muscle action potential amplitude and motor nerve
      conduction velocity, predicted the extent of deterioration of muscle strength or
      physical disability. In adult Charcot-Marie-Tooth type 1A patients, the decline
      in axonal function and in muscle strength may reflect, to a considerable extent,
      a process of normal ageing. The slow increase in physical disability in adulthood
      may well be explained by decreased reserves and compensatory mechanisms together
      with progression of skeletal deformations due to muscle weakness.

PMID- 19843649
TI  - Cerebellar agenesis revisited.
AB  - New clinical and employment information, together with over-looked previously
      published information, on a patient (H.C.) is reviewed. H.C., who died at the age
      of 76 in 1939, was found, by chance during anatomical dissection, to lack a
      cerebellum. This synthesis challenges an unusual and interesting account of
      cerebellar agenesis published in Brain in 1994 by Glickstein (see also
      Glickstein, 2006), in which the allegedly 'bogus' oral history of this
      individual's motor skills was held to have led to 'medical myth making'. Part of
      the burden of the 1994 paper was to show that 'cerebellar agenesis is always
      associated with profound motor deficits'. Glickstein therefore focussed on an
      apparent 'exception' to this conclusion, concerning the brain of a single case,
      H.C., who died 70 years ago, who 'had given rise to an oral tradition alleging
      that normal movement is possible despite total cerebellar agenesis'. Glickstein
      (1994) concludes 'despite an oral tradition to the contrary there is absolutely
      no evidence about the motor capacities of this man during his life'. Rather
      remarkably, an extensive history of this individual has become available, its
      significance becoming noted only this year; this complements and adds to a
      previous brief history published on H.C. (and not mentioned in the 1994 paper;
      see below). The new evidence includes the death certificate stating the man's
      occupation to have been 'manual labourer' with all the implications relevant to
      his supposed incapacity. The written historical record thus confronts the alleged
      'myth'. It is interesting to note how medical records on an undoubtedly very
      ordinary citizen were recorded in London in the 1930s (before the NHS was set up
      in 1949) and how they could be made accessible to clinical colleagues in east
      London in the middle of World War II blitz bombing of the capital.

PMID- 19843648
TI  - Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour
      disorder and Parkinson's disease.
AB  - Idiopathic rapid eye movement sleep behaviour disorder is an important risk
      factor in the development of Parkinson's disease. Numerous potential predictive
      markers of Parkinson's disease may present before motor symptoms emerge, but
      testing of these markers in rapid eye movement sleep behaviour disorder has been
      performed only in small studies. There has been no comparison of markers between
      patients with idiopathic rapid eye movement sleep behaviour disorder and
      Parkinson's disease, and between men and women. We evaluated an array of
      potential Parkinson's disease predictive markers in 159 patients; including 68
      with idiopathic rapid eye movement sleep behaviour disorder, 36 controls, 34
      Parkinson's patients with rapid eye movement sleep behaviour disorder and 21
      Parkinson's patients without rapid eye movement sleep behaviour disorder.
      Compared with controls, patients with idiopathic rapid eye movement sleep
      behaviour disorder demonstrated substantial olfactory loss (P < 0.001). Olfaction
      was more impaired in Parkinson's disease than idiopathic rapid eye movement sleep
      behaviour disorder and did not differ between Parkinson's patients with, or
      without, rapid eye movement sleep behaviour disorder. Numerous measures of motor
      function including the Unified Parkinson Disease Rating Scale alternate tap,
      Purdue Peg Board and Timed 'Up and Go' were impaired in idiopathic rapid eye
      movement sleep behaviour disorder compared with controls (P < 0.01). All of these
      motor measures were worse with Parkinson's disease than with idiopathic rapid eye
      movement sleep behaviour disorder, regardless of rapid eye movement sleep
      behaviour disorder status. Autonomic symptoms and systolic blood pressure drop
      were impaired in patients with idiopathic rapid eye movement sleep behaviour
      disorder compared with controls (P = 0.003). Orthostatic abnormalities in
      Parkinson's disease were found in the group with rapid eye movement sleep
      behaviour disorder (P < 0.001). However, Parkinson's patients without rapid eye
      movement sleep behaviour disorder were not different than controls and had less
      impairment than those with idiopathic rapid eye movement sleep behaviour disorder
      (P = 0.004) and Parkinson's patients with rapid eye movement sleep behaviour
      disorder (P < 0.001). Colour vision was impaired in idiopathic rapid eye movement
      sleep behaviour disorder compared with controls (P < 0.001). However, only
      Parkinson's patients with rapid eye movement sleep behaviour disorder had
      abnormalities significantly different than controls (P < 0.001), and there were
      significant differences between Parkinson's patients with or without rapid eye
      movement sleep behaviour disorder (P < 0.04). Idiopathic rapid eye movement sleep
      behaviour disorder patients had slightly increased harm avoidance scores on
      personality testing (P = 0.04). Other than slightly better performances among
      women in the Purdue Peg Board, there was no difference in any measure between men
      and women, suggesting similar pathogenic processes underlying rapid eye movement
      sleep behaviour disorder. Patients with idiopathic rapid eye movement sleep
      behaviour disorder demonstrate abnormalities in numerous potential markers of
      neurodegenerative disease--these markers are heterogeneous, generally correlate
      with each other and occur equally in men and women. Although these abnormalities
      are usually intermediate between control values and Parkinson's patients,
      autonomic dysfunction and colour vision appear to be more linked to rapid eye
      movement sleep behaviour disorder status than Parkinson's disease, suggesting a
      unique pathophysiology of these abnormalities.

PMID- 19843650
TI  - Ectopic expression of polysialylated neural cell adhesion molecule in adult
      macaque Schwann cells promotes their migration and remyelination potential in the
      central nervous system.
AB  - Recent findings suggested that inducing neural cell adhesion molecule
      polysialylation in rodents is a promising strategy for promoting tissue repair in
      the injured central nervous system. Since autologous grafting of Schwann cells is
      one potential strategy to promote central nervous system remyelination, it is
      essential to show that such a strategy can be translated to adult primate Schwann
      cells and is of interest for myelin diseases. Adult macaque Schwann cells were
      transduced with a lentiviral vector encoding sialyltransferase, an enzyme
      responsible for neural cell adhesion molecule polysialylation. In vitro, we found
      that ectopic expression of polysialylate promoted adult macaque Schwann cell
      migration and improved their integration among astrocytes in vitro without
      modifying their antigenic properties as either non-myelinating or pro
      myelinating. In addition, forced expression of polysialylate in adult macaque
      Schwann cells decreased their adhesion with sister cells. To investigate the
      ability of adult macaque Schwann cells to integrate and migrate in vivo, focally
      induced demyelination was targeted to the spinal cord dorsal funiculus of nude
      mice, and both control and sialyltransferase expressing Schwann cells
      overexpressing green fluorescein protein were grafted remotely from the lesion
      site. Analysis of the spatio-temporal distribution of the grafted Schwann cells
      performed in toto and in situ, showed that in both groups, Schwann cells migrated
      towards the lesion site. However, migration of sialyltransferase expressing
      Schwann cells was more efficient than that of control Schwann cells, leading to
      their accelerated recruitment by the lesion. Moreover, ectopic expression of
      polysialylated neural cell adhesion molecule promoted adult macaque Schwann cell
      interaction with reactive astrocytes when exiting the graft, and their 'chain
      like' migration along the dorsal midline. The accelerated migration of
      sialyltransferase expressing Schwann cells to the lesion site enhanced their
      ability to compete for myelin repair with endogenous cells, while control Schwann
      cells were unable to do so. Finally, remyelination by the exogenous
      sialyltransferase expressing Schwann cells restored the normal distribution of
      paranodal and nodal elements on the host axons. These greater performances of
      sialyltransferase expressing Schwann cell correlated with their sustained
      expression of polysialylated neural cell adhesion molecule at early times when
      migrating from the graft to the lesion, and its progressive downregulation at
      later times during remyelination. These results underline the potential
      therapeutic benefit to genetically modify Schwann cells to overcome their poor
      migration capacity and promote their repair potential in demyelinating disorders
      of the central nervous system.

PMID- 19843651
TI  - Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic
      generalized epilepsies.
AB  - Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a
      predominant genetic aetiology, the genetic factors predisposing to idiopathic
      generalized epilepsies remain elusive. Studies of structural genomic variations
      have revealed a significant excess of recurrent microdeletions at 1q21.1,
      15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric
      disorders including autism, intellectual disability and schizophrenia.
      Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic
      risk factor for common idiopathic generalized epilepsy syndromes, implicating
      that other recurrent microdeletions may also be involved in epileptogenesis. This
      study aimed to investigate the impact of five microdeletions at the genomic
      hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic
      risk to common idiopathic generalized epilepsy syndromes. The candidate
      microdeletions were assessed by high-density single nucleotide polymorphism
      arrays in 1234 patients with idiopathic generalized epilepsy from North-western
      Europe and 3022 controls from the German population. Microdeletions were
      validated by quantitative polymerase chain reaction and their breakpoints refined
      by array comparative genomic hybridization. In total, 22 patients with idiopathic
      generalized epilepsy (1.8%) carried one of the five novel microdeletions compared
      with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8-13.2;
      chi(2) = 26.7; 1 degree of freedom; P = 2.4 x 10(-7)). Microdeletions were
      observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2
      (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and
      22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the
      microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8-13.2; P
      = 4.2 x 10(-4)) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3-74.7;
      P = 0.009). Including nine patients with idiopathic generalized epilepsy in this
      cohort with known 15q13.3 microdeletions (IGE/control: 9/0), parental
      transmission could be examined in 14 families. While 10 microdeletions were
      inherited (seven maternal and three paternal transmissions), four microdeletions
      occurred de novo at 15q13.3 (n = 1), 16p13.11 (n = 2) and 22q11.2 (n = 1). Eight
      of the transmitting parents were clinically unaffected, suggesting that the
      microdeletion itself is not sufficient to cause the epilepsy phenotype. Although
      the microdeletions investigated are individually rare (<1%) in patients with
      idiopathic generalized epilepsy, they collectively seem to account for a
      significant fraction of the genetic variance in common idiopathic generalized
      epilepsy syndromes. The present results indicate an involvement of microdeletions
      at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that
      recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic
      susceptibility effect to a broad range of neuropsychiatric disorders.

PMID- 19843652
TI  - Cerebral oxygen and glucose metabolism in patients with mitochondrial m.3243A>G
      mutation.
AB  - The m.3243A>G mutation is the most common pathogenic mutation in mitochondrial
      DNA. It leads to defective oxidative phosphorylation, decreased oxygen
      consumption and increased glucose utilization and lactate production in vitro.
      However, oxygen and glucose metabolism has not been studied in the brain of
      patients harbouring the m.3243A>G mutation. Therefore, 14 patients with the
      m.3243A>G mutation, not experiencing acute stroke-like episodes and 14 age
      matched controls underwent positron emission tomography using 2-[(18)F]fluoro-2
      deoxyglucose, [(15)O]H(2)O and [(15)O]O(2) as the tracers during normoglycaemia.
      The metabolic rate of oxygen and glucose were determined using a quantitative
      region of interest analysis. Metabolites in unaffected periventricular tissue
      were measured using magnetic resonance spectroscopy. We found that the cerebral
      metabolic rate of oxygen was decreased by 26% (range 18%-29%) in the grey as well
      as the white matter of patients with the m.3243A>G mutation. A decrease in the
      metabolic rate of glucose was found with predilection to the posterior part of
      the brain. No major changes were detected in cerebral blood flow or the number of
      white matter lesions. Our results show that the m.3243A>G mutation leads to a
      global decrease in oxygen consumption in the grey matter including areas where no
      other signs of disease were present.

PMID- 19843653
TI  - Maladaptation of critical cellular functions in asthma: bioinformatic analysis.
AB  - Small maladaptations in cellular response to environmental stressors may underlie
      diseases like asthma. However, genomewide transcriptional profile comparisons
      between case and controls only highlight the quantitatively largest changes.
      Critical cellular homeostatic pathways may be upregulated modestly during normal
      adaptation to stress but insufficiently during disease. To discover such pathways
      in asthma, we utilized public information on differential response of primary
      bronchial epithelial cells from asthmatic or normal subjects to stressors like
      ozone and viral infections. Genes that were upregulated by stressor conditions in
      normal cells but were relatively downregulated in cells from asthmatic subjects
      were selected for further analysis. Either a stringent selection based on
      quantitative criterion or a nonstringent selection followed by network-based
      analysis was used. At the individual gene level, decay accelerating factor-1 (DAF
      1, CD55) was identified and selected for validation. In a mouse model of allergic
      airway inflammation (AAI) resembling asthma, protein expression of CD55 was
      reduced compared with normal mice and returned to normal upon resolution of the
      allergic response. This was consistent with our finding of relative
      downregulation of CD55 in asthmatic compared with normal subjects. Interestingly,
      at a network level, the results pointed to possible abnormalities in the inositol
      signaling pathway, a critical cell signaling mechanism. In the mouse model of
      AAI, we found downregulation of inositol polyphosphate 4 phosphatase A (INPP4A),
      a critical member of the inositol signaling pathway. This and previous genetic
      evidence supports a role for inositol signaling abnormalities in asthma. In
      summary, logic-gated hypothesis-free exploration of published data sets may be
      valuable in discovery of novel disease-associated pathways.

PMID- 19843654
TI  - Terminal differentiation of goat mammary tissue during pregnancy requires the
      expression of genes involved in immune functions.
AB  - Terminal differentiation of mammary tissue into a functional epithelium that
      synthesizes and secretes milk occurs during pregnancy. The molecular mechanisms
      underlying this complex process are poorly understood, especially in ruminants.
      To obtain an overview of the ruminant mammary gland's final differentiation
      process, we conducted time-course gene expression analysis of five physiological
      stages: four during pregnancy (P46, P70, P90, and P110) and one after 40 days of
      lactation (L40). An appropriate loop experimental design was used to follow gene
      expression profiles. Using three nulliparous (pregnancy) or primiparous
      (lactation) goats per stage, we performed a comparison starting from nine dye
      swaps and using a 22K bovine oligoarray. Statistical analysis revealed that the
      expression of 1,696 genes varied significantly at least once in the study. These
      genes fell into 19 clusters based on their expression profiles. Identification of
      biological functions with Ingenuity Pathway Analysis software revealed several
      similarities, in keeping with physiological stages described in mice. As in mice,
      expression of milk protein genes began at midpregnancy, and genes regulating
      lipid biosynthesis were induced at the onset of lactation. During the first half
      of pregnancy, the molecular signature of goat mammary tissue was characterized by
      the expression of genes associated with tissue remodeling and differentiation,
      while the second half was mainly characterized by the presence of messengers
      encoding genes involved in cell proliferation. A large number of immune-related
      genes were also induced, supporting recent speculation that mammary tissue has an
      original immune function, and the recruitment of migrating hematopoietic cells
      possibly involved in the branching morphogenesis of the mammary gland. These data
      hint that the induction of differentiation occurs early in pregnancy, very likely
      before P46. This period is therefore crucial for obtaining a healthy and
      productive mammary gland.

PMID- 19843656
TI  - Exposure-response analysis in patients with schizophrenia to assess the effect of
      asenapine on QTc prolongation.
AB  - An exposure-response (E-R) analysis using linear mixed effects modeling was
      conducted on data from a thorough QTc trial for asenapine in 148 patients with
      schizophrenia. In a parallel design, patients received asenapine 5 mg twice daily
      (BID) for 10 days (10d) followed by 10 mg BID (6d), asenapine 15 mg BID (10d)
      followed by 20 mg BID (6d), quetiapine 375 mg BID (for assay sensitivity; 16d) or
      placebo (16d). Triplicate 12-lead electrocardiograms and concentration
      measurements were obtained on day -1 (baseline), 1, 10, and 16 at 8 scheduled
      times on each day. At mean C(max) for all asenapine doses, the E-R model
      predicted that the mean QTcF increase was less than 5 milliseconds, the
      International Conference on Harmonisation-established threshold for clinical
      concern. The model predicted a mean increase of 7 to 8 milliseconds for
      quetiapine. The corresponding upper bounds of the 95% confidence intervals were
      7.5 milliseconds and 11.2 milliseconds for asenapine and quetiapine,
      respectively.

PMID- 19843655
TI  - Population pharmacokinetics of perphenazine in schizophrenia patients from CATIE:
      impact of race and smoking.
AB  - The goal of the study was to characterize population pharmacokinetics (PPK) for
      perphenazine in patients with schizophrenia from the Clinical Antipsychotic
      Trials of Intervention Effectiveness (CATIE). Patients (n = 156) received 8 to 32
      mg of perphenazine daily for 14 to 600 days for a total of 421 plasma
      concentrations measurements. Nonlinear mixed-effects modeling was used to
      determine PPK characteristics of perphenazine. One- and 2-compartment models with
      various random effect implementations and mixture distributions were evaluated.
      Objective function values and goodness-of-fit plots were used as model selection
      criteria. Age, weight, sex, race, smoking, and concomitant medications were
      evaluated as covariates. A 1-compartment linear model with proportional error
      best described the data. The population mean clearance and volume of distribution
      for perphenazine were 483 L/h and 18 200 L, respectively. Race and smoking status
      had significant impacts on perphenazine clearance estimates. In addition, the
      estimated population mean clearance was 48% higher in nonsmoking African
      Americans than in nonsmoking other races (512 L/h vs 346 L/h). Active smokers
      eliminated perphenazine 159 L/h faster than nonsmokers in each race. Clearances
      for smoking African Americans versus smokers in other races were 671 L/h versus
      505 L/h, respectively.

PMID- 19843657
TI  - Quantitative analysis of T-wave morphology increases confidence in drug-induced
      cardiac repolarization abnormalities: evidence from the investigational IKr
      inhibitor Lu 35-138.
AB  - This study investigates repolarization changes induced by a new candidate drug to
      determine whether a composite electrocardiographic (ECG) measure of T-wave
      morphology could be used as a reliable marker to support the evidence of abnormal
      repolarization, which is indicated by QT interval prolongation. Seventy-nine
      healthy subjects were included in this parallel study. After a baseline day
      during which no drug was given, 40 subjects received an I(Kr)-blocking
      antipsychotic compound (Lu 35-138) on 7 consecutive days while 39 subjects
      received placebo. Resting ECGs were recorded and used to determine a combined
      measure of repolarization morphology (morphology combination score [MCS]), based
      on asymmetry, flatness, and notching. Replicate measurements were used to
      determine reliable change and study power for both measures. Lu 35-138 increased
      the QTc interval with corresponding changes in T-wave morphology as determined by
      MCS. For subjects taking Lu 35-138, T-wave morphology was a more reliable
      indicator of I(Kr) inhibition than QTcF (chi(2) = 20.3, P = .001). At 80% study
      power for identifying a 5-millisecond placebo-adjusted change from baseline for
      QTcF, the corresponding study power for MCS was 93%. As a covariate to the
      assessment of QT interval liability, MCS offered important additive information
      to the effect of Lu 35-138 on cardiac repolarization.

PMID- 19843658
TI  - Second-look arthroscopic findings and clinical outcomes after microfracture for
      osteochondral lesions of the talus.
AB  - BACKGROUND: Arthroscopic microfracture is frequently used to repair osteochondral
      lesions of the talus. However, despite the popularity of this technique, no study
      has been conducted on cartilage repair after microfracture by second-look
      arthroscopy. PURPOSE: The purpose of the present study was to evaluate cartilage
      repair in osteochondral lesions of the talus by second-look arthroscopy and to
      compare arthroscopic findings with clinical outcomes 12 months postoperatively.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Second-look
      arthroscopies were performed in 20 ankles of 19 patients at 12 months
      postoperatively. Arthroscopic findings were classified using the Ferkel and Cheng
      staging system, and cartilage repair was assessed using the International
      Cartilage Repair System (ICRS). Clinical outcomes were evaluated using the
      American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale.
      RESULTS: According to the Ferkel and Cheng staging at second-look arthroscopy, 7
      of the 20 ankles (35%) showed incomplete healing (stage D). In terms of ICRS
      overall repair grades, 8 ankles (40%) were abnormal (grade III). Mean AOFAS
      scores for Ferkel and Cheng stages A to C (n = 13) and stage D (n = 7) were 88.5
      and 82.0 points, and those for ICRS repair grades I and II (n = 12) and grade III
      (n = 8) were 88.7 and 82.5, respectively. Good correlations were found between
      AOFAS scores and Ferkel and Cheng stages and ICRS grades. Overall, 90% of ankles
      achieved an excellent or good AOFAS score of over 80 points. CONCLUSION: Second
      look arthroscopic findings at 12 months postoperatively after microfracture for
      osteochondral lesions of the talus revealed that 40% of lesions were incompletely
      healed. Nevertheless, the majority of patients achieved a good clinical outcome.
      Furthermore, postoperative clinical scores were found to be correlated with ICRS
      repair grades.

PMID- 19843659
TI  - Recognition, expression, and understanding facial expressions of emotion in
      adolescents with nonverbal and general learning disabilities.
AB  - Children with nonverbal learning disabilities (NVLD) have been found to be worse
      at recognizing facial expressions than children with verbal learning disabilities
      (LD) and without LD. However, little research has been done with adolescents. In
      addition, expressing and understanding facial expressions is yet to be studied
      among adolescents with LD subtypes. This study examined abilities of adolescents
      with NVLD, with general learning disabilities (GLD), and without LD to recognize,
      express, and understand facial expressions of emotion. Adolescents were grouped
      into those with NVLD, with GLD, and without LD using the Wechsler Intelligence
      Scale for Children-Third Edition (short form) and Wide Range Achievement Test
      Third Edition. The adolescents completed neuropsychological, recognition,
      expression, and understanding measures. It is intriguing that the GLD group was
      significantly less accurate at recognizing and understanding facial expressions
      compared with the NVLD and NLD groups, who did not differ. Implications are
      explored with regard to the need to consider possible deficits in recognition and
      understanding of emotion in adolescents with LD in schools.

PMID- 19843660
TI  - T cell-based immunotherapy of metastatic renal cell carcinoma: modest success and
      future perspective.
AB  - Metastatic renal cell carcinoma (MRCC) remains a challenging malignancy to treat.
      Cancer immunotherapies have been extensively explored in melanoma and RCC as they
      poorly respond to conventional cytotoxic agents but show responses to a variety
      of immunologic agents. The recent considerable success of T cell-based
      immunotherapy in melanoma warrants further efforts to apply this treatment to
      other cancers including MRCC. Although RCC is an immunosensitive cancer, similar
      attempts in MRCC have shown a very limited success. In this review, we summarize
      the clinical data on T cell-based immunotherapies for MRCC showing the modest
      success that has been achieved to date. More importantly, we discuss potential
      strategies for improving its efficacy for the treatment of MRCC in light of the
      important achievements for treating metastatic melanoma. In particular, the
      growing evidence of success by combining expanded tumor-infiltrating lymphocytes
      with lymphodepletion merits investigation in MRCC. Identifying new RCC-associated
      antigens, optimized methods, and conditions for detection, isolation, and/or
      modification and expansion of tumor-specific T cells are all important strategies
      to be pursued for improving T cell-based immunotherapy of MRCC.

PMID- 19843661
TI  - Macrophage inhibitory cytokine 1: a new prognostic marker in prostate cancer.
AB  - PURPOSE: High serum levels of macrophage inhibitory cytokine 1 (MIC-1) are
      strongly associated with metastatic prostate cancer, suggesting MIC-1 is a
      biomarker for prostate cancer prognosis. EXPERIMENTAL DESIGN: We conducted a
      prospective cohort study of 1,442 Swedish men with a pathologically verified
      diagnosis of prostate cancer between 2001 and 2003. Blood was drawn either
      pretreatment (n = 431) or posttreatment (n = 1,011) and cases were followed for a
      mean time of 4.9 years (range, 0.1-6.8 years). RESULTS: MIC-1 serum levels
      independently predicted poor cancer-specific survival with an almost 3-fold
      higher cancer death rate in patients with serum levels in the highest quartile
      compared with men with serum levels in the lowest quartile (adjusted hazard
      ratio, 2.98; 95% confidence interval, 1.82-4.68). Pretreatment MIC-1 levels
      revealed an even stronger association with disease outcome with an 8-fold higher
      death rate in the highest compared with the lowest category (adjusted hazard
      ratio, 7.98; 95% confidence interval, 1.73-36.86). Among patients considered to
      have localized disease, MIC-1 significantly increased the discriminative capacity
      between indolent and lethal prostate cancer compared with the established
      prognostic markers clinical stage, pathologic grade, and prostate-specific
      antigen level (P = 0.016). A sequence variant in the MIC-1 gene was associated
      with decreased MIC-1 serum levels (P = 0.002) and decreased prostate cancer
      mortality (P = 0.003), suggesting a causative role of MIC-1 in prostate cancer
      prognosis. CONCLUSIONS: Serum MIC-1 concentration is a novel biomarker capable of
      predicting prostate cancer prognosis.

PMID- 19843662
TI  - Circulating mesothelin protein and cellular antimesothelin immunity in patients
      with pancreatic cancer.
AB  - PURPOSE: Mesothelin is a glycoprotein expressed on normal mesothelial cells and
      is overexpressed in several histologic types of tumors including pancreatic
      adenocarcinomas. A soluble form of mesothelin has been detected in patients with
      ovarian cancer and malignant mesothelioma, and has prognostic value. Mesothelin
      has also been considered as a target for immune-based therapies. We conducted a
      study on the potential clinical utility of mesothelin as a biomarker for
      pancreatic disease and therapeutic target pancreatic cancer. EXPERIMENTAL DESIGN:
      Tumor cell-bound and soluble mesothelin in patients was evaluated by
      immunohistochemistry and ELISA, respectively. The in vitro cellular immune
      response to mesothelin was evaluated by INF gamma ELISA and intracellular
      cytokine staining for IFN gamma in CD4(+) and CD8(+) T cells. The level of
      circulating antibodies to mesothelin was measured by ELISA. RESULTS: All tumor
      tissue from patients with pancreatic adenocarcinoma expressed mesothelin (n =
      10). Circulating mesothelin protein was detected in patients with pancreatic
      adenocarcinoma (73 of 74 patients) and benign pancreatic disease (5 of 5) but not
      in healthy individuals. Mesothelin-specific CD4(+) and CD8(+) T cells were
      generated from peripheral blood lymphocytes of patients with pancreatic cancer in
      50% of patients compared with only 20% of healthy individuals. Antibodies
      reactive to mesothelin were detected in <3% of either patients or healthy
      individuals. CONCLUSIONS: Circulating mesothelin is a useful biomarker for
      pancreatic disease. Furthermore, mesothelin-specific T cells can be induced in
      patients with pancreatic cancer. This suggests that mesothelin is a potential
      target for immune-based intervention strategies in pancreatic cancer.

PMID- 19843663
TI  - A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC
      chemotherapy in relapsed and refractory acute myelogenous leukemia.
AB  - PURPOSE: Inhibiting mammalian target of rapamycin (mTOR) signaling in acute
      myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their
      sensitivity to cytotoxic agents. We sought to determine the safety and describe
      the toxicity of this approach by adding the mTOR inhibitor, sirolimus
      (rapamycin), to intensive AML induction chemotherapy. EXPERIMENTAL DESIGN: We
      performed a phase I dose escalation study of sirolimus with the chemotherapy
      regimen MEC (mitoxantrone, etoposide, and cytarabine) in patients with relapsed,
      refractory, or untreated secondary AML. RESULTS: Twenty-nine subjects received
      sirolimus and MEC across five dose levels. Dose-limiting toxicities were
      irreversible marrow aplasia and multiorgan failure. The maximum tolerated dose
      (MTD) of sirolimus was determined to be a 12 mg loading dose on day 1 followed by
      4 mg/d on days 2 to 7, concurrent with MEC chemotherapy. Complete or partial
      remissions occurred in 6 (22%) of the 27 subjects who completed chemotherapy,
      including 3 (25%) of the 12 subjects treated at the MTD. At the MTD, measured
      rapamycin trough levels were within the therapeutic range for solid organ
      transplantation. However, direct measurement of the mTOR target p70 S6 kinase
      phosphorylation in marrow blasts from these subjects only showed definite target
      inhibition in one of five evaluable samples. CONCLUSIONS: Sirolimus and MEC is an
      active and feasible regimen. However, as administered in this study, the synergy
      between MEC and sirolimus was not confirmed. Future studies are planned with
      different schedules to clarify the clinical and biochemical effects of sirolimus
      in AML and to determine whether target inhibition predicts chemotherapy response.

PMID- 19843664
TI  - Regional brain activation during verbal declarative memory in metastatic breast
      cancer.
AB  - PURPOSE: To determine the neurofunctional basis of verbal memory dysfunction in
      women with metastatic breast cancer. This objective was based on previous
      research suggesting memory and other cognitive deficits in this population. We
      attempted to determine if verbal memory impairments were related to the most
      commonly studied disease parameters including adjuvant chemotherapy and chronic
      stress-related disruption of limbic system structures. EXPERIMENTAL DESIGN: We
      used functional magnetic resonance imaging to test our hypothesis that women with
      breast cancer would show significantly lower brain activation during verbal
      declarative memory tasks compared with age and education-matched healthy female
      controls. We also assessed several stress-related variables including diurnal
      cortisol levels to test our hypothesis that women with breast cancer would show
      higher stress and this would contribute to brain activation deficits during
      memory tasks. RESULTS: Women with breast cancer had significantly lower
      prefrontal cortex activation during the memory encoding condition compared with
      controls. However, the breast cancer group showed significantly greater
      activation than controls during the recall condition in multiple, diffuse brain
      regions. There were no significant differences between the groups in stress
      related variables. Women who were treated with cyclophosphamide, methotrexate,
      and 5-fluorouracil chemotherapy showed lower prefrontal cortex activation during
      memory encoding. CONCLUSIONS: These results suggest that women with metastatic
      breast cancer may be at risk for verbal memory impairments as a result of altered
      functional brain activation profiles. These findings may be associated with
      chemotherapy type and/or other aspects of the breast cancer disease process.

PMID- 19843665
TI  - Crosstalk to stromal fibroblasts induces resistance of lung cancer to epidermal
      growth factor receptor tyrosine kinase inhibitors.
AB  - PURPOSE: Lung cancers with epidermal growth factor receptor (EGFR)-activating
      mutations show good clinical response to gefitinib and erlotinib, selective
      tyrosine kinase inhibitors (TKI) to EGFR, but these tumors invariably develop
      drug resistance. Host stromal cells have been found to have a considerable effect
      on the behavior of cancer cells. Little is known, however, about the role of host
      cells on the sensitivity of cancer cells to receptor TKIs. We have therefore
      assessed the effect of crosstalk between stromal cells and lung cancer cells
      harboring EGFR mutations on susceptibility to EGFR-TKIs. EXPERIMENTAL DESIGN: We
      evaluated the gefitinib sensitivity of lung cancer cells with EGFR-activating
      mutations, PC-9 and HCC827, when cocultured with fibroblasts and coinjected into
      severe combined immunodeficient mice. We also examined the effect of lung cancer
      cells to fibroblast recruitment. RESULTS: Both human fibroblast cell lines and
      primary cultured fibroblasts produced various levels of hepatocyte growth factor
      (HGF). Lung cancer cells markedly recruited fibroblasts. The lung cancer cells
      became resistant to EGFR-TKIs when cocultured in vitro with HGF-producing
      fibroblasts and coinjected into severe combined immunodeficient mice.
      Importantly, combined use of gefitinib plus anti-HGF antibody or the HGF
      antagonist, NK4, successfully overcame the fibroblast-induced EGFR-TKI resistance
      both in vitro and in vivo. Colocalization of fibroblasts and HGF was detected in
      both xenograft tumors in mouse model and lung cancer patient specimens.
      CONCLUSIONS: These findings indicate that crosstalk to stromal fibroblasts plays
      a critical role in lung cancer resistance to EGFR-TKIs and may be an ideal
      therapeutic target in lung cancer with EGFR-activating mutations.

PMID- 19843666
TI  - The mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2
      inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and
      colorectal tumor xenografts.
AB  - PURPOSE: Novel molecularly targeted agents, given in combination with
      radiotherapy, have the potential to increase tumor response rates and the
      survival of patients with lung cancer. AZD6244 is a potent and selective
      inhibitor of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2), a
      critical enzyme within the MAPK/extracellular signal-regulated kinase (ERK)
      signaling pathway that regulates the proliferation and survival of tumor cells.
      EXPERIMENTAL DESIGN: This study examined the potential benefit of combining
      AZD6244 with fractionated radiotherapy using human lung and colon carcinoma
      xenograft models. RESULTS: AZD6244 reduced ERK phosphorylation in Calu-6 lung
      cancer cells in vitro. Administration of AZD6244 for 10 days (25 mg/kg twice
      daily p.o.) inhibited the tumor growth of Calu-6 xenografts, with regrowth
      occurring on cessation of drug treatment. When fractionated tumor-localized
      radiotherapy (5 x 2 Gy) was combined with AZD6244 treatment, the tumor growth
      delay was enhanced significantly when compared with either modality alone, and
      this effect was also seen in a colon tumor model. We examined the effect of
      inhibiting MEK1/2 on the molecular responses to hypoxia, a potential interaction
      that could contribute to radioresponsiveness. AZD6244 reduced hypoxia-inducible
      factor-specific transactivation in vivo, shown using Calu-6 dual clone cells that
      stably express a Firefly luciferase gene under the control of a hypoxia-driven
      promoter. Furthermore, hypoxia-inducible factor-1 alpha, GLUT-1, and vascular
      endothelial growth factor levels were reduced by AZD6244, and there was a
      significant decrease in vascular perfusion in the tumors given combination
      treatment when compared with the other treatment groups. CONCLUSIONS: These data
      provide support for the clinical development of AZD6244 in combination with
      radiotherapy and indicate a potential role for AZD6244 in inhibiting the tumor
      hypoxia response.

PMID- 19843667
TI  - Evaluation of an ELISA for p16INK4a as a screening test for cervical cancer.
AB  - BACKGROUND: The low sensitivity of cytology and low specificity of human
      papillomavirus testing prompts searching for more accurate cervical cancer
      screening strategies. Our goal was to evaluate an ELISA-based test for
      p16(INK4a). METHODS: 1,781 women undergoing routine screening provided cervical
      specimens for p16(INK4a) ELISA (original and enhanced versions of a prototype),
      liquid-based cytology, and Hybrid Capture II (hc2) testing. All women with a
      positive result and a random sample of those with negative results on all tests
      were referred for histologic diagnosis. Cervical intraepithelial neoplasia grade
      >or=3 (>or=CIN3) was the main outcome. The original analysis included all
      >or=CIN3 outcomes (n = 28). The a posteriori analysis was used to represent
      clinically relevant results with >or=CIN3 as outcomes only when detected after a
      positive screening test (n = 27). RESULTS: Participants had a median age of 23
      years. The prevalence of high-risk human papillomavirus DNA was 30.6%. In a
      posteriori analyses, the sensitivity and specificity for p16(INK4a) ELISA (>or=8
      pg/mL cut-point), cytology, and hc2 were 50.9%, 58.1%, and 100.0%, respectively,
      and 90.4%, 89.3%, and 69.2%, respectively. Referral to colposcopy of women with
      positive results for hc2 and p16(INK4a) (enhanced ELISA, >or=6 pg/mL cut-point)
      had a sensitivity of 91.8% (95% confidence interval, 79.1-100.0%) and specificity
      of 86.0% (95% confidence interval, 82.0-89.0%). Results of the original analyses
      had similar specificity but substantially lower sensitivity due to the strong
      influence of the single CIN3 case with completely negative screening results.
      CONCLUSIONS: An enhanced version of this prototypic p16(INK4a) ELISA showed
      promise in screening, particularly when combined with hc2.

PMID- 19843668
TI  - An admixture scan in 1,484 African American women with breast cancer.
AB  - African American women with breast cancer present more commonly with aggressive
      tumors that do not express the estrogen receptor (ER) and progesterone receptor
      (PR) compared with European American women. Whether this disparity is the result
      of inherited factors has not been established. We did an admixture-based genome
      wide scan to search for risk alleles for breast cancer that are highly
      differentiated in frequency between African American and European American women,
      and may contribute to specific breast cancer phenotypes, such as ER-negative (ER
      ) disease. African American women with invasive breast cancer (n = 1,484) were
      pooled from six population-based studies and typed at approximately 1,500
      ancestry-informative markers. We investigated global genetic ancestry and did a
      whole genome admixture scan searching for breast cancer-predisposing loci in
      association with disease phenotypes. We found a significant difference in
      ancestry between ER+PR+ and ER-PR- women, with higher European ancestry among
      ER+PR+ individuals, after controlling for possible confounders (odds ratios for a
      0 to 1 change in European ancestry proportion, 2.84; 95% confidence interval,
      1.13-7.14; P = 0.026). Women with localized tumors had higher European ancestry
      than women with non-localized tumors (odds ratios, 2.65; 95% confidence interval,
      1.11-6.35; P = 0.029). No genome-wide statistically significant associations were
      observed between European or African ancestry at any specific locus and breast
      cancer, or in analyses stratified by ER/PR status, stage, or grade. In summary,
      in African American women, genetic ancestry is associated with ER/PR status and
      disease stage. However, we found little evidence that genetic ancestry at any one
      region contributes significantly to breast cancer risk or hormone receptor
      status.

PMID- 19843669
TI  - CYP1A2, GSTM1, and GSTT1 polymorphisms and diet effects on CYP1A2 activity in a
      crossover feeding trial.
AB  - Cytochrome P-450 1A2 (CYP1A2) is a biotransformation enzyme that activates
      several procarcinogens. CYP1A2 is induced by cruciferous and inhibited by
      apiaceous vegetable intake. Using a randomized, crossover feeding trial in
      humans, we investigated the dose effects of cruciferous vegetables and the
      effects of any interaction between cruciferous and apiaceous vegetables on CYP1A2
      activity. We also investigated whether response varied by CYP1A2*1F, GSTM1, and
      GSTT1 genotypes (glutathione S-transferases that metabolize crucifer
      constituents) and whether CYP1A2 activity rebounds after apiaceous vegetables are
      removed from the diet. Participants (N = 73), recruited based on genotypes,
      consumed four diets for two weeks each: low-phytochemical diet (basal), basal
      plus single dose of cruciferous (1C), basal plus double dose of cruciferous (2C),
      and basal plus single dose of cruciferous and apiaceous vegetables (1C+A). CYP1A2
      activity was determined by urine caffeine tests administered at baseline and the
      end of each feeding period. Compared with basal diet, the 1C diet increased
      CYP1A2 activity (P < 0.0001) and the 2C diet resulted in further increases (P <
      0.0001), with men experiencing greater dose-response than women. The 1C+A diet
      decreased CYP1A2 activity compared with the 1C and 2C diets (P < 0.0001 for
      both). Although there was no overall effect of CYP1A2*1F or GSTM1-null/GSTT1-null
      genotypes or genotype-by-diet interactions, there were significant diet response
      differences within each genotype. Additionally, CYP1A2 activity recovered
      modestly one day after the removal of apiaceous vegetables. These results suggest
      complex interactions among dietary patterns, genetic variation, and modulation of
      biotransformation that may not be apparent in observational studies.

PMID- 19843670
TI  - Association of breast cancer susceptibility variants with risk of pancreatic
      cancer.
AB  - BACKGROUND: A number of susceptibility genes are common to breast and pancreatic
      cancer. Recently, several breast cancer susceptibility loci have been identified
      through genome-wide association studies. Here we evaluated possible associations
      between these single nucleotide polymorphisms (SNP) and pancreatic cancer risk.
      METHODS: Ten SNPs from FGFR2, TOX3, MAP3K1, H19, LSP1, chromosome 8q24, CASP8,
      and LUM were investigated for associations with pancreatic cancer risk following
      genotyping in 1,143 Caucasian individuals with pancreatic adenocarcinoma and
      1,097 unaffected controls from a clinic-based pancreatic cancer case-control
      study. RESULTS: CASP8 rs1045485 [odds ratio (OR), 0.78; 95% confidence interval
      (95% CI), 0.65-0.9; P = 0.005] and MAP3K1 rs889312 (OR, 0.85; 95% CI, 0.74-0.97;
      P = 0.017) showed evidence of association with risk of pancreatic cancer. The
      CASP8 rs1045485 association was evident in ever smokers (P = 0.002), but not in
      nonsmokers (P = 0.55), and the effect was strongest in heavy smokers (OR, 0.52;
      95% CI, 0.29-0.93; P = 0.03). In contrast the MAP3K1 rs889312 association was
      only evident in nonsmokers (OR, 0.78; 95% CI, 0.64-0.95; P = 0.01). In addition,
      evaluation of the influence of the 10 SNPs on survival detected significant
      associations between outcome for locally advanced pancreatic cancer cases and
      both 8q rs6983561 (P = 0.045) and LUM rs2268578 (P = 0.02). CONCLUSION:
      Association studies in a large pancreatic case-control study indicate that SNPs
      associated with breast cancer may also be associated with pancreatic cancer
      susceptibility and survival.

PMID- 19843671
TI  - Genetic variants of methyl metabolizing enzymes and epigenetic regulators:
      associations with promoter CpG island hypermethylation in colorectal cancer.
AB  - Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate
      metabolizing enzymes may influence the bioavailability of methyl groups, whereas
      DNA and histone methyltransferases are involved in epigenetic regulation of gene
      expression. We studied associations of genetic variants of folate metabolizing
      enzymes (MTHFR, MTR, and MTRR), DNA methyltransferase DNMT3b, and histone
      methyltransferases (EHMT1, EHMT2, and PRDM2), with colorectal cancers, with or
      without the CpG island methylator phenotype (CIMP), MLH1 hypermethylation, or
      microsatellite instability. Incidence rate ratios were calculated in case-cohort
      analyses, with common homozygotes as reference, among 659 cases and 1,736
      subcohort members of the Netherlands Cohort Study on diet and cancer (n =
      120,852). Men with the MTHFR 677TT genotype were at decreased colorectal cancer
      risk (incidence rate ratio, 0.49; P = 0.01), but the T allele was associated with
      increased risk in women (incidence rate ratio, 1.39; P = 0.02). The MTR 2756GG
      genotype was associated with increased colorectal cancer risk (incidence rate
      ratio, 1.58; P = 0.04), and inverse associations were observed among women
      carrying DNMT3b C-->T (rs406193; incidence rate ratio, 0.72; P = 0.04) or EHMT2 G
      ->A (rs535586; incidence rate ratio, 0.76; P = 0.05) polymorphisms. Although
      significantly correlated (P < 0.001), only 41.5% and 33.3% of CIMP tumors
      harbored MLH1 hypermethylation or microsatellite instability, respectively. We
      observed inverse associations between MTR A2756G and CIMP among men (incidence
      rate ratio, 0.58; P = 0.04), and between MTRR A66G and MLH1 hypermethylation
      among women (incidence rate ratio, 0.55; P = 0.02). In conclusion, MTHFR, MTR,
      DNMT3b, and EHMT2 polymorphisms are associated with colorectal cancer, and rare
      variants of MTR and MTRR may reduce promoter hypermethylation. The incomplete
      overlap between CIMP, MLH1 hypermethylation, and microsatellite instability
      indicates that these related "methylation phenotypes" may not be similar and
      should be investigated separately.

PMID- 19843672
TI  - Sheddase activity of tumor necrosis factor-alpha converting enzyme is increased
      and prognostically valuable in head and neck cancer.
AB  - Tumor necrosis factor alpha converting enzyme (TACE) is a sheddase overexpressed
      in cancers that generates cancer cell growth and survival factors, and is
      implicated in carcinogenesis and tumor growth. This indicates that TACE could be
      a potentially important cancer biomarker. Unexpectedly, TACE expression in cancer
      tissues does not correlate with cancer stage or invasiveness. Although TACE
      sheddase activity is a more direct and potentially better indicator of TACE
      biology and might be a better cancer biomarker than TACE expression, it has not
      been studied in cancer tissues. In the present study, we developed a reliable
      specific assay for quantification of TACE sheddase activity, investigated TACE
      activity and TACE protein expression in head and neck cancer (HNC) tissues, and
      examined the correlation of the results with HNC clinical stages and likelihood
      to recur. We found that HNC cell lines and tissues contained remarkably higher
      quantities of TACE activity and TACE protein than normal keratinocytes or oral
      mucosa. siRNA silencing of TACE resulted in the inhibition of release of the
      tumorogenic factors amphiregulin and transforming growth factor alpha, and tumor
      protective factors tumor necrosis factor receptors from HNC cells. Importantly,
      TACE activity, but not TACE protein expression, was significantly higher in
      large, T3/T4, primary tumors relative to small, T1/T2, primary tumors, and
      especially in primary tumors likely to recur relative to those unlikely to recur.
      These data show that increased TACE activity in cancer is biologically and
      clinically relevant, and indicate that TACE activity could be a significant
      biomarker of cancer prognosis.

PMID- 19843673
TI  - Sequence variant on 3q28 and urinary bladder cancer risk: findings from the Los
      Angeles-Shanghai bladder case-control study.
AB  - Recently, the first genome-wide association study of bladder cancer identified an
      association of genome-wide significance between single nucleotide polymorphism
      (SNP) rs715021 and urinary bladder cancer risk among European individuals. This
      SNP is in a haplotype block in linkage disequilibrium with the TP63 gene. We
      investigated the role of this SNP among 1,042 cases and 1,123 controls among non
      Latino whites in Los Angeles County, CA and among Chinese in Shanghai, China. We
      confirmed an association between the A allele and bladder cancer risk [log
      additive per A allele odds ratios (OR), 1.24; and 95% confidence intervals (95%
      CI), 1.02-1.52; P = 0.032] in Los Angeles County and a similar association in
      Shanghai (log-additive per A allele OR, 1.21; 95% CI, 0.98-1.49; P = 0.080).
      These estimates did not differ by study site, smoking status, or gender. However,
      the effects were greater in older individuals. Analysis within non-Latino whites,
      for whom we had histologic results, revealed that this association was restricted
      to low-risk tumors (OR, 1.49; 95% CI, 1.17-1.92; P = 0.002) and absent among high
      risk tumors (OR, 1.03; 95% CI, 0.80-1.33; P = 0.790; heterogeneity, P = 0.019). A
      positive association (OR, 1.56; 95% CI, 0.93-2.62; P = 0.089) was only observed
      among high-risk tumors from individuals older than 56 years old (interaction, P =
      0.045). Our results suggest that a TP63 gene variant may increase susceptibility
      for the development of urinary bladder tumors with low risk of progression.

PMID- 19843674
TI  - Energy intake and risk of postmenopausal breast cancer: an expanded analysis in
      the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.
AB  - Although animal experiments have consistently shown a positive relationship
      between breast cancer and energy intake, evidence from human studies remains
      inconclusive. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening
      Trial cohort, 29,170 women, ages 55 to 75 years, who successfully completed a
      food frequency questionnaire (FFQ) at entry (1993-2001), were followed through
      2007, and 1,319 incident breast cancers were ascertained (median time from FFQ
      completion to diagnosis, 4.4 years). Women in the highest quartile of energy
      intake, relative to the lowest, had modestly, but significantly, increased breast
      cancer risk [multivariate relative risk (RR), 1.21; 95% confidence interval (95%
      CI), 1.03-1.42; P(trend) = 0.03]. The inclusion of body mass index and physical
      activity in the model reduced risk slightly (RR, 1.18; 95% CI, 1.00-1.39;
      P(trend) = 0.07). However, in similar analyses using energy intake from a FFQ
      administered approximately five years after entry (27,428 women; 806 incident
      breast cancers; median time from FFQ completion to diagnosis, 2.7 years), women
      in the highest and lowest quartiles of energy intake had similar risk. When
      follow-up time after the first FFQ was divided into three 4-year periods, the
      multivariate RRs for high versus low energy intake increased from 1.21 to 1.37 to
      1.55 with increasing time since dietary assessment. Although the divergent
      results for the two FFQs could be due to subtle questionnaire differences, our
      findings suggest a modest positive association between energy intake and
      postmenopausal breast cancer that strengthens with time since dietary assessment.

PMID- 19843675
TI  - Testosterone and biological characteristics of breast cancers in postmenopausal
      women.
AB  - Androgens are involved in the development of breast cancer, although the
      mechanisms remain unclear. To further investigate androgens in breast cancer, we
      examined the relations between serum testosterone and age, body mass index (BMI),
      tumor size, histologic type, grade, axillary node involvement, estrogen receptor
      status, progesterone receptor status, and HER2 overexpression in a cross
      sectional study of 592 postmenopausal breast cancer patients. Mean testosterone
      differences according to categories of patient and tumor characteristics were
      assayed by Fisher's or Kruskall-Wallis test as appropriate; adjusted odds ratios
      (OR) of having a tumor characteristic by testosterone tertiles were estimated by
      logistic regression. Testosterone concentrations were significantly higher in
      women with BMI >or=30 versus BMI <25. ORs of having a tumor >or=2 cm increased
      significantly with increasing testosterone tertiles, and the association was
      stronger in women >/=65 years. The OR of having infiltrating ductal carcinoma was
      significantly higher in the highest compared with the lowest testosterone
      tertile. ORs of having estrogen receptor- and progesterone receptor-negative
      versus estrogen receptor- and progesterone receptor-positive tumors decreased
      significantly with increasing testosterone tertiles. In women >or=70 years, those
      with high testosterone had a significantly greater OR of HER2-negative cancer
      than those with low testosterone. These results support previous findings that
      high-circulating testosterone is a marker of hormone-dependent breast cancer. The
      age-related differences in the association of testosterone with other disease and
      patient characteristics suggest that breast cancers in older postmenopausal women
      differ markedly from those in younger postmenopausal women. The relationship
      between testosterone and HER2 status in the oldest patients merits further
      investigation.

PMID- 19843676
TI  - Reproducibility of fifteen urinary estrogens and estrogen metabolites over a 2-
      to 3-year period in premenopausal women.
AB  - Endogenous estrogens play an integral role in the etiology of breast,
      endometrial, and, possibly, ovarian cancers. Estrogen metabolism yields products
      that are potentially both estrogenic and genotoxic, yet individual metabolic
      patterns are just beginning to be explored in epidemiologic studies. Within the
      Nurses' Health Study II, we examined reproducibility of 15 urinary estrogens and
      estrogen metabolites (EM) among 110 premenopausal women with three luteal-phase
      urine samples collected over 3 years. EM were measured by a recently developed
      high-performance liquid chromatography-tandem mass spectrometry (LC-MS(2)) method
      with high sensitivity, specificity, and precision. We assessed Spearman
      correlations and intraclass correlation coefficients (ICC) across the three
      samples. Correlations between urinary estrone or estradiol and EM were only
      modest (r = 0.1-0.5). The 2- and 4-hydroxylation pathways were highly correlated
      (r = 0.9) but weakly inversely correlated with the 16-hydroxylation pathway (r = 
      0.2). Within-woman reproducibility over time was fairly high for the three
      pathways, with ICCs ranging from 0.52 (16-hydroxylation pathway) to 0.72 (2
      hydroxylation pathway). ICCs were similarly high for 2-catechols and the
      individual catechols (ICCs = 0.58-0.72). Individual and grouped methylated 2
      catechols had fairly high ICCs (0.51-0.62), but methylated 4-catechols had low
      ICCs (0.14-0.27). These data indicate that, in general, urinary EM levels vary
      substantially among individuals compared with intraindividual variability. Within
      person reproducibility over time for most EM measures is comparable to or better
      than that for well-vetted biomarkers such as plasma cholesterol and, in
      postmenopausal women, estradiol.

PMID- 19843677
TI  - Methylation markers for CCNA1 and C13ORF18 are strongly associated with high
      grade cervical intraepithelial neoplasia and cervical cancer in cervical
      scrapings.
AB  - PURPOSE: Recently, we reported 13 possible cervical cancer-specific methylated
      biomarkers identified by pharmacologic unmasking microarray in combination with
      large-genome computational screening. The aim of the present study was to perform
      an in-depth analysis of the methylation patterns of these 13 candidate genes in
      cervical neoplasia and to determine their diagnostic relevance. EXPERIMENTAL
      DESIGN AND RESULTS: Five of the 13 gene promoters (C13ORF18, CCNA1, TFPI2,
      C1ORF166, and NPTX1) were found to be more frequently methylated in frozen
      cervical cancer compared with normal cervix specimens. Quantitative methylation
      analysis for these five markers revealed that both CCNA1 and C13ORF18 were
      methylated in 68 of 97 cervical scrapings from cervical cancer patients and in
      only 5 and 3 scrapings, respectively, from 103 healthy controls (P < 0.0005). In
      cervical scrapings from patients referred with an abnormal Pap smear, CCNA1 and
      C13ORF18 were methylated in 2 of 43 and 0 of 43 CIN 0 (no cervical
      intraepithelial neoplasia) and in 1 of 41 and 0 of 41 CIN I, respectively.
      Furthermore, 8 of 43 CIN II, 22 of 43 CIN III, and 3 of 3 microinvasive cancer
      patients were positive for both markers. Although sensitivity for CIN II or
      higher (for both markers 37%) was low, specificity (96% and 100%, respectively)
      and positive predictive value (92% and 100%, respectively) were high. CONCLUSION:
      Methylation of CCNA1 and C13ORF18 in cervical scrapings is strongly associated
      with CIN II or higher-grade lesions. Therefore, these markers might be used for
      direct referral to gynecologists for patients with a methylation-positive
      scraping.

PMID- 19843678
TI  - Enrichment of low penetrance susceptibility loci in a Dutch familial colorectal
      cancer cohort.
AB  - Recent genome-wide association studies have identified several loci that confer
      an increased risk of colorectal cancer (CRC). We studied the role of the 8q24.21
      (rs6983267), 18q21.1 (rs12953717), 15q13.3 (rs4779584), 11q23.1 (rs3802842),
      8q23.3 (rs16892766), and 10p14 (rs10795668) risk variants in a series of 995
      Dutch CRC cases and 1340 controls. The CRC cases were selected on basis of having
      a family history of CRC and/or early-onset disease. The detailed clinical and
      molecular data available on the cases allowed us to examine the relationship
      between risk variants and clinicopathologic characteristics. We replicated the
      association with an increased risk of CRC cancer for all loci, except 10p14. The
      association with the variant on chromosome 15q13.3 was confirmed for the first
      time. The risks associated with variants in our series were higher (not
      significant) than those previously reported, consistent with our series
      reflecting genetic enrichment. Moreover, we show that familial CRC cases possess
      an increased number of risk alleles compared with solitary CRC cases (early
      onset; mean age at diagnosis of 48.5 years). We also identified a significant
      increase in the number of risk alleles in families with early-onset disease
      (<or=50 years) compared with late-onset families (>50 years). In solitary CRC
      patients, enrichment for risk alleles was not observed, suggesting that other
      causes of increased CRC risk play a role in these cases. Overall, our results
      suggest that clustering of low-risk variants may explain part of the excess risk
      in CRC families.

PMID- 19843679
TI  - Elevated cancer mortality in the relatives of patients with pancreatic cancer.
AB  - Most inherited cancer syndromes are characterized by the familial clustering of
      cancers at several organ sites. To determine if cancers, other than pancreatic
      cancer, cluster in pancreatic cancer kindreds, we examined mortality patterns
      among the relatives of National Familial Pancreatic Tumor Registry probands. Over
      200,000 person-years of follow-up from 8,564 first-degree relatives of probands
      and 1,007 spouse controls were included in these analyses. We compared mortality
      rates of National Familial Pancreatic Tumor Registry participants to US
      population rates using weighed standardized mortality ratios (wSMR). Analyses
      were stratified by family history of pancreatic cancer (sporadic versus
      familial), family history of young onset pancreatic cancer (<50 years), and
      family history score. Cancer mortality was increased in both the relatives of
      sporadic probands [wSMR 1.55, 95% confidence interval (95% CI) 1.39-1.73] and
      familial probands (wSMR 1.41, 95% CI 1.26-1.58). Relatives of familial probands
      had a significantly increased risk of dying from breast (wSMR 1.66, 95% CI 1.15
      2.34), ovarian (wSMR 2.05, 95% CI 1.10-3.49), and bile duct cancers (wSMR 2.89,
      95% CI 1.04-6.39). Relatives of sporadic probands were at increased risk of dying
      from bile duct cancer (wSMR 3.01, 95% CI 1.09-6.67). Relatives of young onset
      probands were at higher risk of dying from cancers of the breast (wSMR 1.98, 95%
      CI 1.01-3.52), colon (wSMR 2.31, 95% CI 1.30-3.81) and prostate (wSMR 2.31, 95%
      CI 1.14-4.20). Increased cancer mortality was not observed in the spouse
      controls. Our results show that relatives of pancreatic cancer patients are at
      higher risk of developing cancers at other sites and highlight the importance of
      complete family history in clinical risk assessment.

PMID- 19843680
TI  - Long-term and recent recreational physical activity and survival after breast
      cancer: the California Teachers Study.
AB  - INTRODUCTION: Long-term physical activity is associated with lower breast cancer
      risk. Little information exists on its association with subsequent survival.
      METHODS: California Teachers Study cohort members provided information in 1995
      1996 on long-term (high school through age 54 years) and recent (past 3 years)
      participation in moderate and strenuous recreational physical activities. The
      3,539 women diagnosed with invasive breast cancer after cohort entry and through
      December 31, 2004, were followed through December 31, 2005. Of these, 460 women
      died, 221 from breast cancer. Moderate and strenuous physical activities were
      combined into low (<or=0.50 h/wk/y of any activity), intermediate (0.51-3.0
      h/wk/y of moderate or strenuous activity but no activity >3.0 h/wk/y), or high
      activity (>3.0 h/wk/y of either activity type). Multivariable relative risks (RR)
      and 95% confidence intervals (95% CI) for mortality were estimated using Cox
      proportional hazards methods, adjusting for race/ethnicity, estrogen receptor
      status, disease stage, and baseline information on comorbidities, body mass
      index, and caloric intake. RESULTS: Women with high or intermediate levels of
      long-term physical activity had lower risk of breast cancer death (RR, 0.53; 95%
      CI, 0.35-0.80; and RR, 0.65; 95% CI, 0.45-0.93, respectively) than women with low
      activity levels. These associations were consistent across estrogen receptor
      status and disease stage, but were confined to overweight women. Deaths due to
      causes other than breast cancer were related only to recent activity.
      CONCLUSIONS: Consistent long-term participation in physical activity before
      breast cancer diagnosis may lower risk of breast cancer death, providing further
      justification for public health strategies to increase physical activity
      throughout the lifespan.

PMID- 19843681
TI  - Colorectal cancer incidence and postmenopausal hormone use by type, recency, and
      duration in cancer prevention study II.
AB  - The Women's Health Initiative randomized trials showed a reduction in colorectal
      cancer risk with the use of estrogen plus progesterone (E + P), but not with
      estrogen alone (E-only), after intervention periods <7 years. Using data from the
      Cancer Prevention Study II Nutrition Cohort, we examined associations of
      colorectal cancer risk with E-only and E + P, including analyses by recency and
      duration of hormone use. During 13.2 years of follow-up, 776 cases of invasive
      colorectal cancer occurred among 67,412 postmenopausal women participants. Cox
      proportional hazards models were used to estimate multivariate-adjusted relative
      risks (RR) and 95% confidence intervals (95% CI) of colorectal cancer for current
      and former hormone users according to hormone type and duration of use. Relative
      to women who never used postmenopausal hormones, current, but not former, use of
      E-only was associated with a reduced risk of colorectal cancer (RR 0.76; 95% CI,
      0.59-0.97). Among current E-only users, duration of use was inversely and
      linearly associated with risk (P(trend) = 0.01). Use of E-only for <5 years was
      not associated with reduced risk, whereas use for >or=20 years was associated
      with a 45% reduction in risk (RR, 0.55; 95% CI, 0.36-0.86). There were no
      statistically significant associations between E + P and colorectal cancer risk.
      Our results suggest a strong inverse association of long-term use of E-only with
      colorectal cancer risk, underscoring the importance of collecting data on
      duration of hormone use in epidemiologic studies of postmenopausal hormones and
      risk of disease.

PMID- 19843682
TI  - Associations between silicone skin cast score, cumulative sun exposure, and other
      factors in the ausimmune study: a multicenter Australian study.
AB  - Past sun exposure is linked to a wide range of disease outcomes but is difficult
      to measure accurately. Silicone skin casts measure skin damage, but some studies
      show that age rather than sun exposure is the most important determinant of cast
      score. We examined skin damage scores from silicone casts of the back of the hand
      in a large adult sample (n = 534) with a broad range of past cumulative UV
      radiation (UVR) doses. Participants were ages 18 to 61 years and resided in one
      of four locations down the eastern Australian seaboard, spanning 27-43 degrees S.
      Data were collected by questionnaire and during a nurse-led interview and
      examination. Silicone casts were graded from 1 to 6, where higher score
      represents greater damage. Higher skin damage score was associated with lighter
      skin pigmentation [adjusted odds ratio (AOR), 4.51; 95% confidence interval (95%
      CI), 2.33-8.75], fairer natural hair color, particularly red hair (AOR, 11.31;
      95% CI, 4.08-31.36), and blue/gray eyes (AOR, 1.72; 95% CI, 1.14-2.59). Higher
      cumulative UVR dose, particularly before age 18 years, was associated with higher
      skin damage score (AOR, 2.06; 95% CI, 1.15-2.67 per 1,000 KJ/m(2)), as was number
      of sunburns, even after adjustment for cumulative UVR dose (AOR, 2.86; 95% CI,
      1.50-5.43 for >10 sunburns ever compared with no sunburns ever). Silicone casts
      of the dorsum of the hand provide a measure of cumulative UVR dose and number of
      sunburns over the lifetime, which persists after adjustment for chronological
      age. They can be used as an objective measure of cumulative past sun exposure in
      epidemiologic studies, but other determinants of skin damage, such as skin
      pigmentation, should be concurrently evaluated.

PMID- 19843684
TI  - Incidence of cancer in finnish families with clinically aggressive and
      nonaggressive prostate cancer.
AB  - BACKGROUND: Clinical features of familial prostate cancer (PCa) and other
      malignancies associated with PCa are poorly described. Using a large family-based
      data registry of histologically confirmed cancers with a 40-year follow-up, we
      sought to determine incidence of cancer in Finnish PCa families, separately for
      clinically aggressive and clinically nonaggressive PCa. METHODS: We calculated
      standardized incidence ratios (SIR) for 5,523 members of 202 families by dividing
      the number of observed cancers (altogether 497 cases) by the number of expected
      cancers. The number of expected cancers is based on the national cancer incidence
      rates. RESULTS: SIR for overall cancer risk, excluding PCa, for male relatives in
      clinically nonaggressive families was 0.7 [95% confidence interval (95% CI), 0.6
      0.8] and in clinically aggressive families 0.8 (95% CI, 0.6-1.0). The respective
      SIRs for women were 1.0 (95% CI, 0.8-1.1) and 1.1 (95% CI, 0.8-1.3). The
      incidence of lung cancer among men was significantly lower than in the general
      population. The SIR for gastric cancer among women was 1.9 in both clinically
      nonaggressive and clinically aggressive families. In clinically aggressive
      families, there was borderline significant excess of cancer of the gallbladder in
      men and liver cancer in women. CONCLUSIONS: The incidence of non-PCa cancers is
      not increased in clinically aggressive or clinically nonaggressive PCa families
      except for stomach cancer among women.

PMID- 19843683
TI  - Selenium supplementation reduced oxidative DNA damage in adnexectomized BRCA1
      mutations carriers.
AB  - Some experimental evidence suggests that BRCA1 plays a role in repair of
      oxidative DNA damage. Selenium has anticancer properties that are linked with
      protection against oxidative stress. To assess whether supplementation of BRCA1
      mutation carriers with selenium have a beneficial effect concerning oxidative
      stress/DNA damage in the present double-blinded placebo control study, we
      determined 8-oxodG level in cellular DNA and urinary excretion of 8-oxodG and 8
      oxoGua in the mutation carriers. We found that 8-oxodG level in leukocytes DNA is
      significantly higher in BRCA1 mutation carriers. In the distinct subpopulation of
      BRCA1 mutation carriers without symptoms of cancer who underwent adnexectomy and
      were supplemented with selenium, the level of 8-oxodG in DNA decreased
      significantly in comparison with the subgroup without supplementation.
      Simultaneously in the same group, an increase of urinary 8-oxoGua, the product of
      base excision repair (hOGG1 glycosylase), was observed. Therefore, it is likely
      that the selenium supplementation of the patients is responsible for the increase
      of BER enzymes activities, which in turn may result in reduction of oxidative DNA
      damage. Importantly, in a double-blinded placebo control prospective study, it
      was shown that in the same patient groups, reduction in cancer incidents was
      observed. Altogether, these results suggest that BRCA1 deficiency contributes to
      8-oxodG accumulation in cellular DNA, which in turn may be a factor responsible
      for cancer development in women with mutations, and that the risk to developed
      breast cancer in BRCA1 mutation carriers may be reduced in selenium-supplemented
      patients who underwent adnexectomy.

PMID- 19843685
TI  - A local area analysis of racial, ethnic, and neighborhood disparities in breast
      cancer staging.
AB  - Few studies have examined the role of neighborhood socioeconomic condition in
      shaping breast cancer disparities in defined local areas. We tested associations
      between three measures of neighborhood socioeconomic condition (poverty, median
      income, and a composite neighborhood score) on breast cancer staging in two urban
      counties of the state of New Jersey. Data for these counties were obtained from
      the New Jersey Surveillance, Epidemiology, and End Results tumor registry and
      were selected because of their large racial/ethnic and socioeconomic diversity
      and pilot prevention efforts taking place in these areas. Our study population
      included Black, Latina, and White women (N = 4,589) diagnosed with breast cancer
      from 1999 to 2004. Each cancer case was geocoded and linked to socioeconomic data
      obtained from the 2000 U.S. census. Census tracts served as proxies for
      neighborhoods. Logistic regression models accounting for clustering of
      individuals within neighborhoods were fitted with Generalized Estimating
      Equations. Women living in neighborhoods with lower versus higher neighborhood
      scores were significantly more likely to have advanced-stage disease (odds ratio,
      1.6; confidence intervals, 1.1-2.3), after adjusting for age at diagnosis and
      race/ethnicity. In analyses stratified by race/ethnicity, results remained
      significant for all neighborhood measures for White and Black women, but not for
      Latinas. Moreover, neighborhood poverty showed a weaker socioeconomic gradient in
      breast cancer staging among White women. Our study findings support the use of a
      multidimensional neighborhood index to better capture differences in cancer
      staging risk across racial/ethnic groups and provides evidence that population
      based cancer data could be used to identify local needs specific to local
      populations.

PMID- 19843686
TI  - Breast cancer recurrence in older women five to ten years after diagnosis.
AB  - Little is known about the risk of recurrence >5 years after diagnosis among older
      breast cancer survivors. A community-based population of women >or=65 years
      diagnosed with early-stage breast cancer who survived disease free for 5 years
      was followed for 5 additional years or until a diagnosis of breast cancer
      recurrence, second primary, death, or loss to follow-up. These 5-year disease
      free survivors (N = 1,277) had primary breast cancers that were node negative
      (77%) and estrogen receptor positive or unknown (86%). Five percent (n = 61)
      developed a recurrence between 5 and 10 years after diagnosis: 25% local, 9.8%
      regional, and 66% distant. Women who were node positive [hazard ratio (HR), 3.9;
      95% confidence interval (95% CI), 1.5-10], had poorly differentiated tumors (HR,
      2.5; 95% CI, 0.9-6.6), or who received breast conserving surgery without
      radiation therapy (HR, 2.4; 95% CI, 1.0-5.8) had higher recurrence rates compared
      with node negative, well differentiated, and receipt of mastectomy, respectively.
      Not receiving adjuvant tamoxifen, compared with receiving adjuvant tamoxifen, was
      also positively associated with late recurrence among women with estrogen
      receptor-positive/unknown tumors. Although relatively few women experience a late
      recurrence, most recurrences present as advanced disease, which is difficult to
      treat in older women. This study of late recurrence emphasizes that the risk,
      although small, is not negligible even in this group at high risk of death due to
      competing causes.

PMID- 19843687
TI  - The relationships between feelings of satisfaction and burden with respect to
      activity and social support among health promotion volunteers in Japan.
AB  - Health promotion volunteers (HPVs) working to promote community health in Japan
      feel both satisfaction and burden with their community engagement activities.
      This study examined the relationship between their satisfaction and burden toward
      their activities and social support. A mail-in self-check questionnaire survey
      was distributed to 604 HPVs in Japan in September 2005. Multiple regression
      analysis showed that high "activity attachment" was associated with more support
      from family, colleagues, and public health nurses; high "personal benefit" was
      associated with more support from colleagues and public health nurses. It was
      also found that low "burden on everyday life" was associated with more support
      from family and colleagues and that low "psychological burden" was associated
      with more support from colleagues and community members. It became clear that
      social support from various sources was positively related to HPVs' satisfaction
      and negatively related to HPVs' burden with their activities. To encourage HPV
      activities, it is important to consider what kinds of social support would be
      most useful to increase the satisfaction and reduce the burden felt by HPVs.

PMID- 19843688
TI  - Identification of actively translated mRNA transcripts in a rat model of early
      stage colon carcinogenesis.
AB  - With respect to functional mapping of gene expression signatures, the steady
      state mRNA expression level does not always accurately reflect the status of
      critical signaling proteins. In these cases, control is exerted at the epigenetic
      level of recruitment of mRNAs to polysomes, the factories of ribosomes that
      mediate efficient translation of many cellular messages. However, to date, a
      genome-wide perspective of the effect of carcinogen and chemoprotective bioactive
      diets on actively translated (polysomal) mRNA populations has not been done.
      Therefore, we used an established colon cancer model, i.e., the azoxymethane
      (AOM)-treated rat, in combination with a chemoprotective diet extensively studied
      in our laboratory, i.e., n-3 polyunsaturated fatty acids, to characterize the
      molecular processes underlying the transformation of normal colonic epithelium.
      The number of genes affected by AOM treatment 10 weeks after carcinogen injection
      was significantly greater in the polysome RNA fraction compared with the total
      RNA fraction as determined using a high-density microarray platform. In
      particular, polysomal loading patterns of mRNAs associated with the Wnt-beta
      catenin, phospholipase A(2)-eicosanoid and the mitogen-activated protein kinase
      signaling axes were significantly upregulated at a very early period of tumor
      development in the colon. These data indicate that translational alterations are
      far more extensive relative to transcriptional alterations in mediating malignant
      transformation. In contrast, transcriptional alterations were found to be more
      extensive relative to translational alterations in mediating the effects of diet.
      Therefore, during early stage colonic neoplasia, diet and carcinogen seem to
      predominantly regulate gene expression at multiple levels via unique mechanisms.

PMID- 19843689
TI  - Elevated levels of urinary prostaglandin e metabolite indicate a poor prognosis
      in ever smoker head and neck squamous cell carcinoma patients.
AB  - Cyclooxygenase (COX)-derived prostaglandin E(2) (PGE(2)) plays a role in the
      development and progression of several tumor types including head and neck
      squamous cell carcinoma (HNSCC). Measurements of urinary PGE metabolite (PGE-M)
      can be used as an index of systemic PGE(2) production. In ever smokers, increased
      levels of urinary PGE-M reflect increased COX-2 activity. In this study, we
      determined whether baseline levels of urinary PGE-M were prognostic for ever
      smoker HNSCC patients. A retrospective chart review of ever smoker HNSCC patients
      treated with curative intent was done. Fifteen of 31 evaluable patients developed
      progressive disease (recurrence or a second primary tumor) after a median follow
      up of 38 months. There were no statistically significant differences between
      patients with (n = 15) or without disease progression (n = 16) with regard to
      stage, site, treatment received, smoking status, and aspirin use during follow
      up. Median urinary PGE-M levels were significantly higher in HNSCC patients with
      disease progression (21.7 ng/mg creatinine) compared with patients without (13.35
      ng/mg creatinine; P = 0.03). Importantly, patients with high baseline levels of
      urinary PGE-M had a significantly greater risk of disease progression (hazard
      ratio, 4.76, 95% CI, 1.31-17.30; P < 0.01) and death (hazard ratio, 9.54; 95% CI,
      1.17-77.7; P = 0.01) than patients with low baseline levels of urinary PGE-M.
      These differences were most evident among patients with early-stage disease.
      Taken together, our findings suggest that high baseline levels of urinary PGE-M
      indicate a poor prognosis in HNSCC patients. Possibly, HNSCC patients with high
      COX-2 activity manifested by elevated urinary PGE-M will benefit from treatment
      with a COX-2 inhibitor.

PMID- 19843690
TI  - Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the
      development of allergic airways disease.
AB  - Allergic asthma is an inflammatory disease of the lung characterized by abnormal
      T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular
      mechanisms leading to the generation of T(H)2 responses remain unclear, although
      toll-like receptors (TLRs) present on innate immune cells play a pivotal role in
      sensing molecular patterns and in programming adaptive T cell responses. Here we
      show that in vivo activation of TLR4 by house dust mite antigens leads to the
      induction of allergic disease, a process that is associated with expression of a
      unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)
      126 suppressed the asthmatic phenotype, resulting in diminished T(H)2 responses,
      inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus
      hypersecretion. miR-126 blockade resulted in augmented expression of POU domain
      class 2 associating factor 1, which activates the transcription factor PU.1 that
      alters T(H)2 cell function via negative regulation of GATA3 expression. In
      summary, this study presents a functional connection between miRNA expression and
      asthma pathogenesis, and our data suggest that targeting miRNA in the airways may
      lead to anti-inflammatory treatments for allergic asthma.

PMID- 19843691
TI  - Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the
      antibiotic tigecycline.
AB  - Persistence of tissue spirochetes of Borrelia burgdorferi as helices and round
      bodies (RBs) explains many erythema-Lyme disease symptoms. Spirochete RBs
      (reproductive propagules also called coccoid bodies, globular bodies, spherical
      bodies, granules, cysts, L-forms, sphaeroplasts, or vesicles) are induced by
      environmental conditions unfavorable for growth. Viable, they grow, move and
      reversibly convert into motile helices. Reversible pleiomorphy was recorded in at
      least six spirochete genera (>12 species). Penicillin solution is one unfavorable
      condition that induces RBs. This antibiotic that inhibits bacterial cell wall
      synthesis cures neither the second "Great Imitator" (Lyme borreliosis) nor the
      first: syphilis. Molecular-microscopic techniques, in principle, can detect in
      animals (insects, ticks, and mammals, including patients) helices and RBs of live
      spirochetes. Genome sequences of B. burgdorferi and Treponema pallidum
      spirochetes show absence of >75% of genes in comparison with their free-living
      relatives. Irreversible integration of spirochetes at behavioral, metabolic, gene
      product and genetic levels into animal tissue has been documented. Irreversible
      integration of spirochetes may severely impair immunological response such that
      they persist undetected in tissue. We report in vitro inhibition and destruction
      of B. burgdorferi (helices, RBs = "cysts") by the antibiotic Tigecycline (TG;
      Wyeth), a glycylcycline protein-synthesis inhibitor (of both 30S and 70S ribosome
      subunits). Studies of the pleiomorphic life history stages in response to TG of
      both B. burgdorferi and Treponema pallidum in vivo and in vitro are strongly
      encouraged.

PMID- 19843692
TI  - Priming integrin alpha5 promotes human mesenchymal stromal cell osteoblast
      differentiation and osteogenesis.
AB  - Adult human mesenchymal stromal cells (hMSCs) have the potential to differentiate
      into chondrogenic, adipogenic, or osteogenic lineages, providing a potential
      source for tissue regeneration. An important issue for efficient bone
      regeneration is to identify factors that can be targeted to promote the
      osteogenic potential of hMSCs. Using transcriptome analysis, we found that
      integrin alpha5 (ITGA5) expression is up-regulated during dexamethasone-induced
      osteoblast differentiation of hMSCs. Gain-of-function studies showed that ITGA5
      promotes the expression of osteoblast phenotypic markers and in vitro
      osteogenesis of hMSCs. Down-regulation of endogenous ITGA5 using specific shRNAs
      blunted osteoblast marker gene expression and osteogenic differentiation.
      Molecular analyses showed that the enhanced osteoblast differentiation induced by
      ITGA5 was mediated by activation of focal adhesion kinase/ERK1/2-MAPKs and PI3K
      signaling pathways. Remarkably, activation of endogenous ITGA5 using agonists
      such as a specific antibody that primes the integrin or a peptide that
      specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K
      signaling and to promote osteoblast differentiation and osteogenic capacity of
      hMSCs. Importantly, we demonstrated that hMSCs engineered to overexpress ITGA5
      exhibited a marked increase in their osteogenic potential in vivo. Taken
      together, these findings not only reveal that ITGA5 is required for osteoblast
      differentiation of adult hMSCs but also provide a targeted strategy using ITGA5
      agonists to promote the osteogenic capacity of hMSCs. This may be used for tissue
      regeneration in bone disorders where the recruitment or capacity of hMSCs is
      compromised.

PMID- 19843693
TI  - HPV E6 protein interacts physically and functionally with the cellular telomerase
      complex.
AB  - Telomerase activation is critical for the immortalization of primary human
      keratinocytes by the high-risk HPV E6 and E7 oncoproteins, and this activation is
      mediated in part by E6-induction of the hTERT promoter. E6 induces the hTERT
      promoter via interactions with the cellular ubiquitin ligase, E6AP, and with the
      c-Myc and NFX-1 proteins, which are resident on the promoter. In the current
      study we demonstrate that E6 protein interacts directly with the hTERT protein.
      Correlating with its ability to bind hTERT, E6 also associates with telomeric DNA
      and with endogenous active telomerase complexes. Most importantly, E6 increases
      the telomerase activity of human foreskin fibroblasts transduced with the hTERT
      gene, and this activity is independent of hTERT mRNA expression. Unlike its
      ability to degrade p53, E6 does not degrade hTERT protein in vitro or in vivo.
      Our studies of E6/hTERT interactions also reveal that the C-terminal tagged hTERT
      protein, although incapable of immortalizing fibroblasts, does immortalize
      keratinocytes in collaboration with the viral E7 protein. Thus, E6 protein
      mediates telomerase activation by a posttranscriptional mechanism and these
      findings provide a model for exploring the direct modulation of cell
      telomerase/telomere function by an oncogenic virus and suggest its potential role
      in both neoplasia and virus replication.

PMID- 19843694
TI  - Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites
      contributes to inflammatory hyperalgesia.
AB  - Transient receptor potential vanilloid 1 (TRPV1) plays a major role in
      hyperalgesia and allodynia and is expressed both in the peripheral and central
      nervous systems (CNS). However, few studies have evaluated mechanisms by which
      CNS TRPV1 mediates hyperalgesia and allodynia after injury. We hypothesized that
      activation of spinal cord systems releases endogenous TRPV1 agonists that evoke
      the development of mechanical allodynia by this receptor. Using in vitro
      superfusion, the depolarization of spinal cord triggered the release of oxidized
      linoleic acid metabolites, such as 9-hydroxyoctadecadienoic acid (9-HODE) that
      potently activated spinal TRPV1, leading to the development of mechanical
      allodynia. Subsequent calcium imaging and electrophysiology studies demonstrated
      that synthetic oxidized linoleic acid metabolites, including 9-HODE, 13-HODE, and
      9 and 13-oxoODE, comprise a family of endogenous TRPV1 agonists. In vivo studies
      demonstrated that intrathecal application of these oxidized linoleic acid
      metabolites rapidly evokes mechanical allodynia. Finally, intrathecal
      neutralization of 9- and 13-HODE by antibodies blocks CFA-evoked mechanical
      allodynia. These data collectively reveal a mechanism by which an endogenous
      family of lipids activates TRPV1 in the spinal cord, leading to the development
      of inflammatory hyperalgesia. These findings may integrate many pain disorders
      and provide an approach for developing analgesic drugs.

PMID- 19843695
TI  - Profiling translatomes of discrete cell populations resolves altered cellular
      priorities during hypoxia in Arabidopsis.
AB  - Multicellular organs are composed of distinct cell types with unique assemblages
      of translated mRNAs. Here, ribosome-associated mRNAs were immunopurified from
      specific cell populations of intact seedlings using Arabidopsis thaliana lines
      expressing a FLAG-epitope tagged ribosomal protein L18 (FLAG-RPL18) via
      developmentally regulated promoters. The profiling of mRNAs in ribosome
      complexes, referred to as the translatome, identified differentially expressed
      mRNAs in 21 cell populations defined by cell-specific expression of FLAG-RPL18.
      Phloem companion cells of the root and shoot had the most distinctive
      translatomes. When seedlings were exposed to a brief period of hypoxia, a
      pronounced reprioritization of mRNA enrichment in the cell-specific translatomes
      occurred, including a ubiquitous rise in 49 mRNAs encoding transcription factors,
      signaling proteins, anaerobic metabolism enzymes, and uncharacterized proteins.
      Translatome profiling also exposed an intricate molecular signature of
      transcription factor (TF) family member mRNAs that was markedly reconfigured by
      hypoxia at global and cell-specific levels. In addition to the demonstration of
      the complexity and plasticity of cell-specific populations of ribosome-associated
      mRNAs, this study provides an in silico dataset for recognition of differentially
      expressed genes at the cell-, region-, and organ-specific levels.

PMID- 19843696
TI  - Discrimination between docking and fusion of liposomes reconstituted with
      neuronal SNARE-proteins using FCS.
AB  - Neuronal exocytosis is mediated by the SNARE proteins synaptobrevin 2/VAMP,
      syntaxin 1A, and SNAP-25A. While it is well-established that these proteins
      mediate membrane fusion after reconstitution in artificial membranes, it has so
      far been difficult to monitor intermediate stages of the reaction. Using a
      confocal two-photon setup, we applied fluorescence cross-correlation spectroscopy
      (FCCS) and fluorescence lifetime analysis to discriminate between docking and
      fusion of liposomes. We show that liposome populations that are either non
      interacting, or are undergoing docking and fusion, as well as multiple
      interactions can be quantitatively discriminated without the need for
      immobilizing the lipid bilayers. When liposomes containing a stabilized syntaxin
      1A/SNAP-25A complex were mixed with liposomes containing synaptobrevin 2, we
      observed that rapid docking precedes fusion. Accordingly, docked intermediates
      accumulated in the initial phase of the reaction. Furthermore, rapid formation of
      multiple docked states was observed with on average four liposomes interacting
      with each other. When liposomes of different sizes were compared, only the rate
      of lipid mixing depended on the liposome size but not the rate of docking. Our
      results show that under appropriate conditions a docked state, mediated by trans
      SNARE interactions, can be isolated that constitutes an intermediate in the
      fusion pathway.

PMID- 19843697
TI  - Comparison of Alzheimer Abeta(1-40) and Abeta(1-42) amyloid fibrils reveals
      similar protofilament structures.
AB  - We performed mass-per-length (MPL) measurements and electron cryomicroscopy (cryo
      EM) with 3D reconstruction on an Abeta(1-42) amyloid fibril morphology formed
      under physiological pH conditions. The data show that the examined Abeta(1-42)
      fibril morphology has only one protofilament, although two protofilaments were
      observed with a previously studied Abeta(1-40) fibril. The latter fibril was
      resolved at 8 A resolution showing pairs of beta-sheets at the cores of the two
      protofilaments making up a fibril. Detailed comparison of the Abeta(1-42) and
      Abeta(1-40) fibril structures reveals that they share an axial twofold symmetry
      and a similar protofilament structure. Furthermore, the MPL data indicate that
      the protofilaments of the examined Abeta(1-40) and Abeta(1-42) fibrils have the
      same number of Abeta molecules per cross-beta repeat. Based on this data and the
      previously studied Abeta(1-40) fibril structure, we describe a model for the
      arrangement of peptides within the Abeta(1-42) fibril.

PMID- 19843698
TI  - Conservatism and diversification of plant functional traits: Evolutionary rates
      versus phylogenetic signal.
AB  - The concepts of niche conservatism and adaptive radiation have played central
      roles in the study of evolution and ecological diversification. With respect to
      phenotypic evolution, the two processes may be seen as opposite ends of a
      spectrum; however, there is no straightforward method for the comparative
      analysis of trait evolution that will identify these contrasting scenarios.
      Analysis of the rate of phenotypic evolution plays an important role in this
      context and merits increased attention. In this article, independent contrasts
      are used to estimate rates of evolution for continuous traits under a Brownian
      motion model of evolution. A unit for the rate of phenotypic diversification is
      introduced: the felsen, in honor of J. Felsenstein, is defined as an increase of
      one unit per million years in the variance among sister taxa of ln-transformed
      trait values. The use of a standardized unit of measurement facilitates
      comparisons among clades and traits. Rates of diversification of three functional
      traits (plant height, leaf size, and seed size) were estimated for four to six
      woody plant clades (Acer, Aesculus, Ceanothus, Arbutoideae, Hawaiian lobeliads,
      and the silversword alliance) for which calibrated phylogenies were available.
      For height and leaf size, rates were two to approximately 300 times greater in
      the Hawaiian silversword alliance than in the other clades considered. These
      results highlight the value of direct estimates of rates of trait evolution for
      comparative analysis of adaptive radiation, niche conservatism, and trait
      diversification.

PMID- 19843699
TI  - Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain
      fatty acids and its implications for HIV infection.
AB  - Integration of HIV-1 linear DNA into the host chromatin is an essential step in
      the viral life cycle. However, the majority of reverse-transcribed, nuclear
      imported viral genomes remain episomal, either as linear or circular DNA. To
      date, these nonintegrated viral genomes are largely considered "dead-end
      products" of reverse transcription. Indeed, limited gene expression from
      nonintegrated HIV-1 has been reported, although the mechanism that renders
      nonintegrating HIV-1 genomes incapable of supporting efficient viral replication
      has not been fully elucidated. Here, we demonstrate that nonintegrating HIV-1 and
      HIV-1-based vector genomes are organized into chromatin structures and enriched
      with histone modifications typical of transcriptionally silenced chromatin. Gene
      expression and replication of nonintegrating HIV-1 was notably increased in vitro
      upon exposure to histone deacetylase inhibitors (HDACi) in the form of various
      short-chain fatty acids (SCFAs) known to be endogenously produced by normal
      microbial-gut flora. Furthermore, we demonstrated genetic and functional
      crosstalk between episomal and integrated vector/viral genomes, resulting in
      recombination between integrated and nonintegrated HIV-1, as well as mobilization
      of episomal vector genomes by productive viral particles encoded by integrated
      viral genomes. Finally, we propose a mechanism describing the role of episomal
      HIV-1 forms in the viral life cycle in a SCFA-rich gut environment.

PMID- 19843700
TI  - The Environmental Health/Home Safety Education Project: a successful and
      practical U.S.-Mexico border initiative.
AB  - The Environmental Health/Home Safety Education Project (Proyecto de Salud
      Ambiental y Seguridad en el Hogar) has been developed in response to a wide array
      of severe and often preventable environmental health issues occurring in and
      around homes on the U.S.-Mexico border. Utilizing well-trained community members,
      called promotoras , homes are visited and assessed for potential environmental
      hazards, including home fire and food safety issues. Data analyzed from project
      years 2002 to 2005 shows a significant impact in knowledge levels and initial
      behavior change among targeted participants as it relates to fire and food safety
      issues. Since the initiation of the project in 1999, hundreds of participants
      have improved their quality of life by making their homes safer. The project has
      proven to be sustainable, replicable, flexible, and attractive to funders.

PMID- 19843701
TI  - Understanding the decision-making process for health promotion programming at
      small to midsized businesses.
AB  - This study explores the decision-making process for implementing and continuing
      health promotion programs at small to midsized businesses to inform health
      promotion practitioners and researchers as they market their services to these
      businesses. Qualitative interviews are conducted with 24 employers located in the
      Pacific Northwest ranging in size from 75 to 800 employees, with the majority
      having between 100 and 200 employees. Small to midsized employers depend most on
      company success-related factors rather than on humanitarian motives when deciding
      whether to adopt workplace health promotion programs. They rely heavily on health
      insurers for health promotion and desire more information about the actual costs
      and cost-benefits of programs. To increase health promotion adoption at small to
      midsized businesses, health promotion practitioners should appeal to overall
      company success-related factors, use the insurance channel, and target their
      information to both human resource personnel and senior management.

PMID- 19843702
TI  - Promoting policy and environmental change using photovoice in the Kaiser
      Permanente Community Health Initiative.
AB  - Creative ways must be found to engage both community residents and political
      leaders around policy and environmental solutions to public health issues.
      Photovoice is a community-based, participatory approach to documentary
      photography that provides people with training on photography, ethics, critical
      discussion, and policy advocacy. Photovoice projects have been implemented across
      the nation as part of Kaiser Permanente's Community Health Initiative-a community
      based obesity prevention effort. This article focuses on the first Photovoice
      project implemented in three communities in Colorado. Photovoice themes related
      to healthy eating and active living include a lack of access to healthy food
      choices in stores and schools, unsafe street crossings and sidewalks, and the
      need to redevelop certain areas to encourage safe recreation. The involvement of
      policy leaders in the project combined with several dissemination activities has
      contributed to healthier food offerings in schools and neighborhoods and city
      planning efforts that emphasize walkability and access to healthy food, and park
      revitalization.

PMID- 19843703
TI  - Methods for the cultural adaptation of a diabetes lifestyle intervention for
      Latinas: an illustrative project.
AB  - Because Latinas experience a high prevalence of type 2 diabetes and its
      complications, there is an urgent need to reach them with interventions that
      promote healthful lifestyles. This article illustrates a sequential approach that
      took an effective multiple-risk-factor behavior-change program and adapted it for
      Latinas with type 2 diabetes. Adaptation stages include (a) information gathering
      from literature and focus groups, (b) preliminary adaptation design, and (c)
      preliminary adaptation test. In this third stage, a pilot study finds that
      participants were highly satisfied with the intervention and showed improvement
      across diverse outcomes. Key implications for applications include the importance
      of a model for guiding cultural adaptations, and the value of procedures for
      obtaining continuous feedback from staff and participants during the preliminary
      adaptation test.

PMID- 19843704
TI  - Thymic stromal lymphopoietin induces chemotactic and prosurvival effects in
      eosinophils: implications in allergic inflammation.
AB  - Thymic stromal lymphopoietin (TSLP) is highly expressed by bronchial epithelial
      cells and skin keratinocytes in allergic diseases. TSLP acts as a master switch
      for allergic inflammation through the activation of dendritic cells and mast
      cells for initiating inflammatory type 2 T-helper lymphocyte responses. To
      elucidate the immunological cascades of epithelium/keratinocyte-eosinophil
      mediated allergic inflammation, we examined the modulating effects of TSLP on
      human eosinophils. Expression of TSLP receptor complex was detected by RT-PCR,
      flow cytometry, and Western blot. Adhesion molecules, cytokine, and chemokines
      were quantitated by flow cytometry or ELISA. Intracellular signal transduction
      molecules were measured by Western blot and flow cytometry. We observed that
      human eosinophils constitutively expressed functional heterodimeric TSLP receptor
      complex comprising TSLP-binding chain TSLPR and IL-7Ralpha chain. TSLP could
      significantly delay eosinophil apoptosis, up-regulate cell surface expression of
      adhesion molecule CD18 and intercellular adhesion molecule-1, but down-regulate L
      selectin, enhance eosinophil adhesion onto fibronectin, and induce the release of
      inflammatory cytokine IL-6 and chemokines CXCL8, CXCL1, and CCL2 (all P < 0.05).
      All these effects were concentration dependent and TSLP specific. TSLP regulated
      the above effects through the activation of extracellular signal-regulated
      protein kinase, p38 mitogen-activated protein kinase, and NF-kappaB signaling
      pathway, but not signal transducer and activator of transcription 5 and 3, which
      were usually activated in other effector cells upon TSLP stimulation.
      Collectively, the above findings elucidate the proallergic mechanisms of TSLP via
      the activation of distinct intracellular signaling pathways in eosinophils.

PMID- 19843705
TI  - Protein thiol oxidation in murine airway epithelial cells in response to
      naphthalene or diethyl maleate.
AB  - Naphthalene (NA) is a semivolatile aromatic hydrocarbon to which humans are
      exposed from a variety of sources. NA results in acute cytotoxicity to
      respiratory epithelium in rodents. Cytochrome P450-dependent metabolic activation
      to form reactive intermediates and loss of soluble cellular thiols (glutathione)
      are critical steps in NA toxicity, but the precise mechanisms by which this
      chemical results in cellular injury remain unclear. Protein thiols are likely
      targets of reactive NA metabolites. Loss of these, through adduction or thiol
      oxidation mechanisms, may be important underlying mechanisms for NA toxicity. To
      address the hypothesis that loss of thiols on specific cellular proteins is
      critical to NA-induced cytotoxicity, we compared reduced to oxidized thiol ratios
      in airway epithelial cell proteins isolated from lungs of mice treated with NA or
      the nontoxic glutathione depletor, diethyl maleate (DEM). At 300 mg/kg doses, NA
      administration resulted in a greater than 85% loss of glutathione levels in the
      airway epithelium, which is similar to the loss observed after DEM treatment.
      Using differential fluorescent maleimide labeling followed by 2DE separation of
      proteins, we identified more than 35 unique proteins that have treatment-specific
      differential sulfhydryl oxidation. At doses of NA and DEM that produce similar
      levels of glutathione depletion, Cy3/Cy5 labeling ratios were statistically
      different for 16 nonredundant proteins in airway epithelium. Proteins identified
      include a zinc finger protein, several aldehyde dehydrogenase variants, beta
      actin, and several other structural proteins. These studies show distinct
      patterns of protein thiol alterations with the noncytotoxic DEM and the cytotoxic
      NA.

PMID- 19843706
TI  - Acute lung injury but not sepsis is associated with increased colony formation by
      peripheral blood mononuclear cells.
AB  - Acute lung injury (ALI) and severe sepsis are common critical illnesses
      associated with the mobilization of bone marrow-derived cells into the
      circulation. By identifying and determining these cells' functional
      characteristics, unique prognostic biomarkers can be developed to help
      investigators understand the mechanisms underlying the pathophysiology of these
      disorders. We previously demonstrated an increased colony-forming unit (CFU)
      ability of circulating peripheral blood mononuclear cells (PBMCs) in patients
      with ALI, compared with healthy control subjects, that also correlated with
      improved survival. Here we hypothesized that the increased CFUs in ALI are
      associated with lung injury, and therefore ALI will result in an increased number
      of CFUs compared with patients exhibiting severe sepsis. To test this, blood was
      collected from 80 patients (63 with ALI, and 17 with severe sepsis) within 72
      hours of diagnosis, and from 5 healthy control subjects. A CFU assay was
      performed on isolated PBMCs. Lung injury scores and the need for mechanical
      ventilation were greater in patients with ALI than in patients with severe sepsis
      (P < 0.0001 for each). CFU numbers were highest in patients with ALI compared
      with patients manifesting severe sepsis or control subjects (median CFU number
      [25-75% quartiles] of 61 [13-104] versus 17 [3-34] versus 5 [2-13], P < 0.0005).
      A trend toward improved survival was demonstrated in patients with high (> or =
      48) CFUs (P = 0.06). No relationship between CFUs and mechanical ventilation was
      evident. Our findings suggest that increased colony-forming ability by PBMCs in
      ALI results from lung injury, independent of sepsis and mechanical ventilation.
      Factors contributing to colony formation by PBMCs in ALI, and the role PBMCs play
      in its pathogenesis remain to be fully established.

PMID- 19843708
TI  - Expression of transient receptor potential C6 channels in human lung macrophages.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with pulmonary
      inflammation with increased numbers of macrophages located in the parenchyma.
      These macrophages have the capacity to mediate the underlying pathophysiology of
      COPD; therefore, a better understanding of their function in chronic inflammation
      associated with this disease is vital. Ion channels regulate many cellular
      functions; however, their role in macrophages is unclear. This study examined the
      expression and function of transient receptor potential (TRP) channels in human
      macrophages. Human alveolar macrophages and lung tissue macrophages expressed
      increased mRNA and protein for TRPC6 when compared with monocytes and monocyte
      derived macrophages. Moreover, TRPC6 mRNA expression was significantly elevated
      in alveolar macrophages from patients with COPD compared with control subjects.
      There were no differences in mRNA for TRPC3 or TRPC7. Although mRNA for TRPM2 and
      TRPV1 was detected in these cells, protein expression could not be determined.
      Fractionation of lung-derived macrophages demonstrated that TRPC6 protein was
      more highly expressed by smaller macrophages compared with larger macrophages.
      Using whole-cell patch clamp electrophysiology, TRPC6-like currents were measured
      in both macrophage subpopulations with appropriate biophysical and basic
      pharmacological profiles. These currents were active under basal conditions in
      the small macrophages. These data suggest that TRPC6-like channels are functional
      on human lung macrophages, and may be associated with COPD.

PMID- 19843707
TI  - Matrix metalloproteinase-19 deficiency promotes tenascin-C accumulation and
      allergen-induced airway inflammation.
AB  - Matrix metalloproteinases (MMPs) recently appeared as key regulators of
      inflammation, allowing the recruitment and clearance of inflammatory cells and
      modifying the biological activity of many peptide mediators by cleavage. MMP-19
      is newly described, and it preferentially cleaves matrix proteins such as
      collagens and tenascin-C. The role of MMP-19 in asthma has not been described to
      date. The present study sought to assess the expression of MMP-19 in a murine
      asthma model, and to address the biological effects of MMP-19 deficiency in mice.
      Allergen-exposed, wild-type mice displayed increased expression of MMP-19 mRNA
      and an increased number of MMP-19-positive cells in the lungs, as detected by
      immunohistochemistry. After an allergen challenge of MMP-19 knockout (MMP-19(-/
      )) mice, exacerbated eosinophilic inflammation was detected in bronchoalveolar
      lavage fluid and bronchial tissue, along with increased airway responsiveness to
      methacholine. A shift toward increased T helper-2 lymphocyte (Th2)-driven
      inflammation in MMP-19(-/-) mice was demonstrated by (1) increased numbers of
      cells expressing the IL-33 receptor T(1)/ST(2) in lung parenchyma, (2) increased
      IgG(1) levels in serum, and (3) higher levels of IL-13 and eotaxin-1 in lung
      extracts. Tenascin-C was found to accumulate in peribronchial areas of MMP-19(-/
      ) after allergen challenges, as assessed by Western blot and immunohistochemistry
      analyses. We conclude that MMP-19 is a new mediator in asthma, preventing
      tenascin-C accumulation and directly or indirectly controlling Th2-driven airway
      eosinophilia and airway hyperreactivity. Our data suggest that MMP-19 may act on
      Th2 inflammation homeostasis by preventing the accumulation of tenascin protein.

PMID- 19843710
TI  - An evolutionary perspective on chronic obstructive pulmonary disease.

PMID- 19843711
TI  - TLR2 plays a role in the activation of human resident renal stem/progenitor
      cells.
AB  - In the past few years, adult renal progenitor/stem cells (ARPCs) have been
      identified in human kidneys, and particularly in Bowman's capsule and proximal
      tubules. They may play an important role in the kidney regenerative processes and
      might prospectively be the ideal cell type for the treatment of both acute and
      chronic renal injury. In this study, microarray analysis identified 6 gene
      clusters that discriminated normal human glomerular and tubular ARPCs from renal
      proximal tubular epithelial cells and mesenchymal stem cells. The top-scored
      pathway in the ARPC gene expression profile contained growth factor receptors and
      immune system-related genes, including toll-like receptor 2 (TLR2). Stimulation
      of TLR2 by ligands that mime inflammatory mediators or damage associated
      molecular pattern molecules induced secretion of elevated amounts of monocyte
      chemoattractant protein-1 (MCP-1), IL-6, IL-8, and C3 via NF-kappaB activation.
      TLR2 stimulation also increased the ARPC proliferation rate, suggesting a role
      for TLR2 in ARPC activation via autocrine signaling. Moreover, TLR2 stimulation
      improved ARPC differentiation into renal epithelial cells and was responsible of
      ARPC branching morphogenesis and tubule-like structures formation. For the first
      time, this study provides a genomic characterization of renal multipotent
      progenitor cells and shows that TLR2 found on ARPCs might be responsible for
      their activation in the kidney, orchestrating the activation of crucial signaling
      networks necessary for renal repair.

PMID- 19843712
TI  - Toll-like receptor ligands induce polymorphonuclear leukocyte migration: key
      roles for leukotriene B4 and platelet-activating factor.
AB  - Activation of toll-like receptors (TLRs) and polymorphonuclear leukocyte (PMN)
      accumulation at infection sites are critical events of host defense. The
      involvement of leukotriene (LT) B(4) and platelet-activating factor (PAF) in TLR
      ligand-induced activation of inflammatory cell functions is essentially unknown.
      Using an in vitro model of human PMN migration through human endothelial cell
      monolayers, we demonstrate that prototypic ligands of TLR1/2, 2/6, 3, 4, 5, and
      7/8 promote PMN migration, an effect markedly inhibited by 3 LTB(4) receptor
      antagonists (70-80% inhibition at 100 nM compared to vehicle-treated cells), 3
      PAF receptor antagonists (20-50% inhibition at 10 nM), 3 LT biosynthesis
      inhibitors (75-85% inhibition at 100 nM), and 1 cytosolic phospholipase A(2)alpha
      (cPLA(2)alpha) inhibitor (90% inhibition at 1 microM). Accordingly, selected TLR
      ligands caused Ser-505-phosphorylation of cPLA(2)alpha and measurable LTB(4) and
      PAF biosynthesis in the transmigration assay. As negative controls, interleukin-8
      and formyl-methionyl-leucyl-phenylalanine-elicited migration in vitro was not
      inhibited either by an LTB(4) receptor antagonist or by the cPLA(2)alpha
      inhibitor. Finally, LTB(4) and PAF receptor antagonists inhibited (up to
      approximately 65% at optimal doses) TLR ligand-induced PMN infiltration in the
      mouse air-pouch model. These studies unravel the critical involvement of de novo
      LTB(4) and PAF biosynthesis in PMN migration elicited by TLR ligands.

PMID- 19843713
TI  - Colonic dilation.

PMID- 19843714
TI  - Spectrum of imaging findings in immunocompromised patients with HHV-6 infection.
AB  - OBJECTIVE: The aim of this article is to review systemic manifestations of human
      herpes virus 6 (HHV-6) associated diseases in immunocompromised patients.
      CONCLUSION: The spectrum of HHV-6 associated disorders is broad, but radiologists
      are frequently not familiar with these disorders. In the clinical setting of
      acute infection in an immunocompromised patient, the presence of one of these
      findings (e.g., limbic encephalitis; atypical interstitial pneumonia;
      pericarditis or myocarditis; or, less commonly, gastrointestinal or hepatobiliary
      disorders) should raise the suspicion of a possible HHV-6 related complication.

PMID- 19843715
TI  - Three-dimensional phase-sensitive inversion-recovery turbo FLASH sequence for the
      evaluation of left ventricular myocardial scar.
AB  - OBJECTIVE: The purpose of this study was to evaluate a new free-breathing 3D
      phase-sensitive inversion-recovery (PSIR) turbo FLASH pulse sequence for the
      detection of left ventricular myocardial scar. SUBJECTS AND METHODS: Patients
      with suspected myocardial scar were examined on a 1.5-T MR scanner for myocardial
      late enhancement after the administration of gadopentetate dimeglumine using a
      segmented 2D PSIR turbo FLASH sequence followed by a navigator-gated 3D PSIR
      turbo FLASH sequence. Image quality was scored by two independent readers using a
      4-point Likert scale (0 = poor, nondiagnostic; 1 = fair, diagnostics may be
      impaired; 2 = good, some artifacts but not interfering in diagnostics; 3 =
      excellent, no artifacts). Scars were compared quantitatively in volume and graded
      qualitatively on the basis of size (area) and location. RESULTS: Thirty-three
      patients were scanned using both techniques. In 25 patients, the quality of the
      3D PSIR images was acceptable. Scars were detected in 12 patients. Hyperenhanced
      scar volumes (p = 0.43), qualitative analysis of scar area (p = 0.78), and scar
      location (p = 0.68) were similar for both techniques. More small hyperenhanced
      scars, corresponding mostly to nonischemic distribution patterns, were detected
      using 3D PSIR than 2D PSIR. Although 2D and 3D results were found to be highly
      correlated for scar volume, Bland-Altman analysis indicated a systematic smaller
      infarct volume on the 2D PSIR scans (R(2) = 0.84). CONCLUSION: Free-breathing 3D
      PSIR turbo FLASH imaging is a promising technique for the assessment of left
      ventricular scar particularly for scar quantification and the detection of small
      nonischemic scars in the myocardium.

PMID- 19843716
TI  - Evaluation of mechanical heart valve size and function with ECG-gated 64-MDCT.
AB  - OBJECTIVE: The purpose of our study was to determine whether CT can accurately
      evaluate mechanical heart valve size and function. MATERIALS AND METHODS: Sixty
      two patients with mechanical valves (37 single-disc, 27 bileaflet; 59 aortic, 5
      mitral) were evaluated with ECG-gated 64-MDCT and transthoracic echocardiography;
      a subset of 10 patients underwent cinefluoroscopy. Two readers independently
      interpreted each study. RESULTS: The mean age of the patients was 46.4 +/- 14.4
      years; 50 were men and 12 were women. There was excellent correlation, and
      differences between CT readers were absent to small in measuring the opening
      angle (r = 0.96, p < 0.001; 76.7 +/- 9.0 degrees vs 76.8 +/- 9.6 degrees , p =
      0.73), annulus diameter (r = 0.96, p < 0.001; 25.9 +/- 3.3 vs 25.9 +/- 3.2 mm, p
      = 0.62), and geometric orifice area (r = 0.98, p < 0.001; 3.8 +/- 0.9 vs 3.6 +/-
      0.8 cm(2), p < 0.001). There was strong correlation without difference in opening
      angle between CT and cinefluoroscopy (r = 0.77, p < 0.001; 79.2 degrees +/- 9.8
      degrees vs 77.2 degrees +/- 15.5 degrees , p = 0.45). Compared with manufacturer
      specifications, CT reported opening angles that were smaller for single-disc
      valves (n = 36, 67.4 degrees +/- 5.7 degrees vs 75 degrees , p < 0.001) and
      similar for bileaflet valves (n = 42 for 21 valves, 83.8 degrees +/- 3.9 degrees
      vs 85 degrees , p = 0.05), valves, with small underestimation with CT versus
      specifications in annulus diameter (n = 41; r = 0.75, p < 0.001; 26.4 +/- 3.0 vs
      27.5 +/- 3.3 mm, p = 0.003), and geometric orifice area (n = 35; r = 0.90, p <
      0.001; 3.7 +/- 0.7 vs 3.8 +/- 0.8 cm(2), p = 0.04). Each disc closed fully on CT;
      none had more than mild regurgitation on echocardiography. CONCLUSION: CT can
      measure the size and function of mechanical valves with high interobserver
      agreement and results similar to specifications. The opening angle with CT
      strongly correlates with cinefluoroscopy. CT is promising for the assessment of
      mechanical valves.

PMID- 19843717
TI  - Performance of radiologists in detection of small pulmonary nodules on chest
      radiographs: effect of rib suppression with a massive-training artificial neural
      network.
AB  - OBJECTIVE: A massive-training artificial neural network is a nonlinear pattern
      recognition tool used to suppress rib opacity on chest radiographs while soft
      tissue contrast is maintained. We investigated the effect of rib suppression with
      a massive-training artificial neural network on the performance of radiologists
      in the detection of pulmonary nodules on chest radiographs. MATERIALS AND
      METHODS: We used 60 chest radiographs; 30 depicted solitary pulmonary nodules,
      and 30 showed no nodules. A stratified random-sampling scheme was used to select
      the images from the standard digital image database developed by the Japanese
      Society of Radiologic Technology. The mean diameter of the 30 pulmonary nodules
      was 14.7 +/- 4.1 (SD) mm. Receiver operating characteristic analysis was used to
      evaluate observer performance in the detection of pulmonary nodules first on the
      chest radiographs without and then on the radiographs with rib suppression. Seven
      board-certified radiologists and five radiology residents participated in this
      observer study. RESULTS: For all 12 observers, the mean values of the area under
      the best-fit receiver operating characteristic curve for images without and with
      rib suppression were 0.816 +/- 0.077 and 0.843 +/- 0.074; the difference was
      statistically significant (p = 0.019). The mean areas under the curve for images
      without and with rib suppression were 0.848 +/- 0.059 and 0.883 +/- 0.050 for the
      seven board-certified radiologists (p = 0.011) and 0.770 +/- 0.081 and 0.788 +/-
      0.074 for the five radiology residents (p = 0.310). CONCLUSION: In the detection
      of pulmonary nodules, evaluation of a combination of rib-suppressed and original
      chest radiographs significantly improved the diagnostic performance of
      radiologists over the use of chest radiographs alone.

PMID- 19843718
TI  - Identification and management of persistently active brachytherapy seed implants.
AB  - OBJECTIVE: The purpose of this article is to review the history of permanently
      implanted brachytherapy sources and to establish methods of identifying radon
      sources and discussing appropriate management. CONCLUSION: There are likely
      thousands of people bearing radon seeds that continue to emit radiation decades
      after implantation. They can be identified by clinical history and emission of
      characteristic x-rays. Surgical removal of these sources is rarely warranted.

PMID- 19843719
TI  - Bone biopsy of new suspicious bone lesions in patients with primary carcinoma:
      prevalence and probability of an alternative diagnosis.
AB  - OBJECTIVE: We sought to assess the probability that a new suspicious bone lesion
      is an alternative diagnosis, that is, a benign lesion or a second malignant tumor
      as opposed to metastatic disease from the malignant tumor, in a person with known
      primary malignant disease. MATERIALS AND METHODS: We reviewed the radiologic and
      pathologic records of bone biopsies scheduled at our institution between 2002 and
      2007. The following parameters were recorded: indication, type of primary cancer,
      date of diagnosis, complications of biopsy, whether the sample was of diagnostic
      quality, pathologic finding, and thus whether the primary malignant tumor was
      concordant with the lesion sampled. RESULTS: Fifty-four of 55 patients (17 men,
      37 women; mean age, 67 years) with known primary cancer and suspicious bone
      lesions underwent biopsy. One of the 55 patients did not undergo biopsy because a
      sacral insufficiency fracture was confidently diagnosed at CT. The primary
      malignant disease had been diagnosed up to 16 years before the new bone lesion
      was suspected and bone biopsy performed. Cancer types included those of
      genitourinary tract, breast, thyroid, gastrointestinal tract, and lung and
      lymphoma and myeloma. Diagnostic material was obtained in 43 of 54 cases (80%),
      and nondiagnostic material was obtained in 11 of 54 cases (20%). Forty-two of 43
      positive biopsy findings (98%) were consistent with the primary malignant tumor.
      The other positive finding was a new malignant tumor. This new tumor was
      myelofibrosis in a man with chronic myelocytic leukemia. The primary diagnosis
      correlated highly with that of the new bone lesion (Spearman's test, R = 0.842; p
      < 0.001). No complications, including hemorrhage, infection, sinus track
      formation, fracture, and pneumothorax, were encountered. CONCLUSION: In a patient
      with known primary malignant disease, the probability is low (2%) that biopsy of
      a new suspicious bone lesion will show the lesion is other than metastasis from
      the primary tumor.

PMID- 19843721
TI  - Interobserver agreement in assessing the sonographic and elastographic features
      of malignant thyroid nodules.
AB  - OBJECTIVE: The objective of our study was to investigate interobserver agreement
      for the diagnosis of malignant thyroid nodules using conventional B-mode
      ultrasound and real-time freehand ultrasound elastography. MATERIALS AND METHODS:
      Between December 2007 and February 2008, 45 patients (age range, 19-73 years;
      mean age +/- SD, 45.0 +/- 12.2 years) with 52 thyroid nodules were examined with
      conventional B-mode ultrasound and real-time freehand ultrasound elastography.
      All the patients were scheduled to undergo thyroid surgery because a thyroid
      nodule had been proven malignant on aspiration cytology. Three radiologists
      independently performed conventional ultrasound and elastography and analyzed the
      ultrasound images. Using conventional ultrasound, observers recorded the
      following information about nodular features: composition (solid, cystic, or
      mixed cystic-solid), echogenicity (hyperechoic, isoechoic, hypoechoic, or
      markedly hypoechoic), margin (well circumscribed, microlobulated, or irregular),
      calcification (negative [no calcifications]; microcalcification,
      macrocalcification, or mixed-type calcifications), and shape (parallel or
      nonparallel). Observers determined the Ueno classification and area ratio for
      each nodule using ultrasound elastography. Interobserver agreement was evaluated
      with Spearman's correlation analysis for all findings except the area ratio, for
      which Pearson's correlation analysis was used. A p < 0.05 was considered to
      indicate statistical significance. RESULTS: Statistically significant (p < 0.05)
      concordance among the three radiologists was found on conventional ultrasound for
      most features except echogenicity and margin of thyroid nodules. The highest
      value of concordance on conventional ultrasound was achieved for composition
      (Spearman's correlation coefficient, 0.70-1.00), followed by shape (0.48-0.79)
      and calcification (0.47-0.62). The least concordant findings on conventional
      ultrasound were nodular echogenicity (0.04-0.45) and margin (0.03-0.29). However,
      there was no statistically significant concordance on elastography for the Ueno
      classification (Spearman's correlation coefficient, 0.08-0.22; p > 0.05) or the
      area ratio (Pearson's correlation coefficient, -0.03 to 0.23; p > 0.05).
      CONCLUSION: Statistically significant concordance among radiologists about most
      features of malignant thyroid nodules was seen with conventional ultrasound;
      however, ultrasound elastography did not show reliable interobserver agreement
      for the diagnosis of malignant thyroid nodules.

PMID- 19843720
TI  - T2 measurements of cartilage in osteoarthritis patients with meniscal tears.
AB  - OBJECTIVE: The objective of this study was to quantitatively assess cartilage
      degeneration via T2 mapping to compare patients with and those without meniscal
      tears. SUBJECTS AND METHODS: Thirty-seven patients (18 men, mean age +/- SD, 65.7
      +/- 7.8 years; 19 women, mean age, 63.8 +/- 12.0 years) with clinical symptoms of
      osteoarthritis were studied on 3-T MRI using a 2D multiecho spin-echo sequence
      for T2 mapping. Meniscal signal and morphology were qualitatively graded and
      correlated to the T2 values of cartilage. Analysis of covariance, Bonferroni
      multiple comparison correction, and Spearman's correlation coefficients were used
      for statistical analysis. RESULTS: Patients with meniscal tears (median +/-
      interquartile range, 50.1 +/- 6.1 milliseconds) had significantly (p = 0.021)
      higher T2 values of cartilage than those without meniscal tears (45.7 +/- 4.8
      milliseconds). T2 values of cartilage were significantly higher in the medial
      compartment than in the lateral compartment in patients with medial meniscal
      tears (p = 0.018). CONCLUSION: T2 measurements are increased in patients with
      meniscal tears; this finding adds support to the theory of an association of
      osteoarthritis with damage to both the menisci and hyaline cartilage.

PMID- 19843722
TI  - Percutaneous radiofrequency ablation of hepatocellular carcinoma: assessment of
      safety in patients with ascites.
AB  - OBJECTIVE: The objective of our study was to assess whether percutaneous
      radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a safe
      procedure in patients with ascites. MATERIALS AND METHODS: From October 2005 to
      January 2008, 35 patients with one or more HCCs and ascites were referred to our
      department for planning sonography of RFA. In 15 patients, RFA was determined to
      be unfeasible. One patient was excluded from the study because of the absence of
      ascites at the time of RFA. Percutaneous ultrasound-guided RFA was performed in
      the remaining 19 patients with 24 HCCs. The electrode tract was cauterized at the
      time of electrode removal. Retrospective assessments of the preprocedural
      platelet counts and prothrombin times were performed, and patients were evaluated
      for bleeding complication by checking vital signs, checking serum hemoglobin
      level, and using CT to determine whether the attenuation value of ascites had
      increased > 30 HU. RESULTS: There were no cases of mortality or major
      complications that developed after RFA. No significant difference in the maximum
      thickness of the perihepatic ascites and in the hemoglobin level between the pre-
      and postprocedural measurements was detected. Hemoperitoneum as a minor
      complication was noted in two (10.5%) of 19 patients. However, in those two
      patients, vital signs were stable, follow-up laboratory data were normal, and
      hemoperitoneum had been completely absorbed on CT images obtained 1 month after
      RFA. CONCLUSION: Percutaneous RFA for HCC can be performed safely in patients
      with ascites.

PMID- 19843723
TI  - Air embolism and needle track implantation complicating CT-guided percutaneous
      thoracic biopsy: single-institution experience.
AB  - OBJECTIVE: The objective of our study was to present the details and incidence of
      air embolism and needle track implantation in patients who underwent percutaneous
      CT-guided thoracic biopsy. MATERIALS AND METHODS: We retrospectively reviewed
      1,400 percutaneous CT-guided thoracic biopsies during the period from August 1993
      to August 2008. A case with air embolism was considered to be a patient with
      hypotension during or after biopsy and with an air embolism confirmed on CT. A
      needle track implantation was considered to be a mass in the needle track on the
      postbiopsy follow-up CT. RESULTS: There were three (0.21%) cases of air embolism.
      Air embolisms were confirmed in the left ventricle, coronary artery, ascending
      aorta, and pulmonary vein. The pulmonary venous wall was pathologically
      identified in one case. Although there were no fatalities, two patients needed
      resuscitation. Left hemiplegia occurred in one case, but it gradually
      disappeared. There were four (0.56%) cases of needle track implantation in 713
      pathologically proven malignant thoracic biopsy cases with follow-up CT scans.
      Two were primary lung cancer and the others were lung metastasis (renal cell
      carcinoma and osteosarcoma). Implantation was found 4-7 months (mean, 5.6 months)
      after the biopsy, and size was 2.5-5.6 cm (mean, 3.5 cm). CONCLUSION: The
      incidence of air embolism with clinical symptoms and needle track implantation
      complicating percutaneous thoracic biopsy is more frequent than the previously
      reported rate.

PMID- 19843724
TI  - In vivo imaging of the aneurysm wall with MRI and a macrophage-specific contrast
      agent.
AB  - OBJECTIVE: Because of their capability of secreting proteinases, macrophages play
      a central role in the growth and rupture of aneurysms. Noninvasive imaging of
      macrophages therefore may yield valuable information about the pathogenesis of
      aneurysm disease. We studied uptake of the macrophage-specific contrast agent
      ultrasmall paramagnetic iron oxide (USPIO) in the walls of aneurysms and normal
      sized aortas. MATERIALS AND METHODS: Six patients with an aortic and five
      patients with an iliac aneurysm and 11 age-matched controls were identified in a
      database of 239 patients who underwent evaluations for the staging of prostate
      cancer. USPIO-enhanced MRI and contrast-enhanced MDCT were performed for all
      patients. The presence of USPIO was assessed with an iron-sensitive MRI sequence.
      Quantification consisted of counting the number of quadrants with USPIO-induced
      subendothelial signal voids. A chi-square test was used to analyze the
      significance of the difference between the number of USPIO-positive quadrants in
      the aneurysm group and that in the control group. RESULTS: The number of USPIO
      positive quadrants was significantly higher in the aneurysm than in the control
      group: 158 quadrants (4.2%) in the aneurysm group and 13 quadrants (0.4%) in the
      control group (p < 0.001). Two abdominal aortic aneurysms accounted for 90%
      (154/171) of all USPIO-positive quadrants. CONCLUSION: USPIO uptake is limited or
      absent in the wall of normal-sized aortas and most aneurysms. However, individual
      abdominal aortic aneurysms exhibit high levels of USPIO uptake, indicative of
      extensive macrophage infiltration in the aneurysm wall. Future research should
      focus on the predictive value of USPIO uptake for growth and rupture of
      aneurysms.

PMID- 19843725
TI  - Cement leakage in percutaneous vertebroplasty for osteoporotic compression
      fractures with or without intravertebral clefts.
AB  - OBJECTIVE: The purpose of our study was to compare the incidence and location of
      cement leakage in percutaneous vertebroplasty for osteoporotic compression
      fractures with and without intravertebral clefts. MATERIALS AND METHODS:
      Percutaneous vertebroplasty was performed in 120 consecutive patients with 300
      osteoporotic compression fractures. The cement volume injected was recorded. The
      cement leakage was evaluated using spinal radiography, MRI, and fluoroscopy
      during the procedure and CT after the procedure. RESULTS: One hundred seven
      vertebrae contained intervertebral clefts, and 193 vertebrae had no clefts. The
      cement volume injected (+/- SD) was 4.0 +/- 2.0 and 3.6 +/- 1.6 mL into vertebrae
      with clefts and without clefts, respectively, with no statistically significant
      difference (p = 0.14). There was no statistically significant difference in the
      incidence of cement leakage between vertebrae with clefts (53 of 107) and those
      without clefts (78 of 193) (p = 0.13). Leakage occurred into the epidural veins
      (12 of 107), perivertebral soft tissues (7 of 107), disks (41 of 107),
      intervertebral foramen (1 of 107), and spinal canal (1 of 107) in fractures with
      clefts and into the epidural veins (47 of 193), perivertebral soft tissues (13 of
      193), disks (25 of 193), paravertebral veins (5 of 193), large vein (2 of 193),
      lung (2 of 193), intervertebral foramen (1 of 193), and spinal canal (1 of 193)
      in fractures without clefts. Cement leakage into the epidural vein was
      significantly more frequent in vertebrae without clefts (p < 0.01). Disk leakage
      was significantly more frequent in vertebrae with clefts compared with those
      without clefts (p < 0.01). CONCLUSION: There was no statistically significant
      difference in the incidence of cement leakage between vertebrae with clefts and
      without clefts. However, cement leakage into the epidural vein was significantly
      more frequent in vertebrae without clefts and disk leakage was significantly more
      frequent in vertebrae with clefts.

PMID- 19843726
TI  - Transcatheter arterial chemoembolization for hepatocellular carcinoma after
      attempted portal vein embolization in 25 patients.
AB  - OBJECTIVE: Portal vein embolization (PVE) has been widely used to facilitate
      major liver resection; however, curative surgery even after PVE may not be
      possible mainly because of inadequate hypertrophy of remnant liver or disease
      progression. For these patients, transcatheter arterial chemoembolization (TACE)
      is the next therapeutic option. We evaluated the safety and efficacy of TACE
      after PVE in 25 patients with hepatocellular carcinoma (HCC). CONCLUSION: TACE
      using a single chemotherapeutic agent can be performed safely and effectively in
      HCC patients who previously underwent PVE. TACE after PVE allowed two of the
      patients to be downstaged so they could undergo surgical resection.

PMID- 19843727
TI  - Biopsy method: a major predictor of adherence after benign breast biopsy?
AB  - OBJECTIVE: Adopting a longitudinal approach to assess women after breast biopsy
      with a benign result, this study aimed to comparatively evaluate the effect of
      the biopsy method on compliance with clinical recommendations for follow-up.
      MATERIALS AND METHODS: For this study, 410 patients who underwent biopsy of a
      breast lesion were included: fine-needle aspiration biopsy, n = 95 patients; core
      biopsy, n = 84; local excision under local anesthesia, n = 72; vacuum-assisted
      breast biopsy, n = 100; and hookwire localization, n = 59. Information about
      patient age, place of residence, whether complications occurred, and type of
      lesion was collected. RESULTS: Compliance was higher among women who had
      undergone vacuum-assisted breast biopsy than those who had undergone one of the
      other biopsy methods. The superiority (carryover effect) of vacuum-assisted
      breast biopsy persisted for 18 months after the biopsy procedure. Patient
      compliance for all of the other biopsy methods followed an M pattern, with the
      peaks corresponding to the follow-up mammography sessions. In patients who had
      undergone vacuum-assisted breast biopsy, a gradual decrease in compliance over
      time was observed. Older women were more compliant than younger women with follow
      up recommendations regardless of biopsy method. A subanalysis of the vacuum
      assisted breast biopsy group indicated that complications are associated with
      better compliance. CONCLUSION: Women more often adhere to clinical
      recommendations for follow-up sessions comprising mammography. Patient age and
      whether biopsy complications occurred also seem to modify compliance. Further
      studies should assess whether superior compliance after vacuum-assisted breast
      biopsy persists in other settings, such as with stereotactic or ultrasound
      guidance, different numbers of cores, and procedures of various durations.

PMID- 19843728
TI  - Time-resolved MR angiography as a useful sequence for assessment of ovarian vein
      reflux.
AB  - OBJECTIVE: The purpose of this retrospective study was to assess the imaging
      characteristics of ovarian vein reflux using time-resolved MR angiography (TR
      MRA). One hundred consecutive female patients underwent TR-MRA of the pelvis to
      evaluate suspected or known pelvic pathology. Findings of ovarian vein reflux,
      ovarian vein dilation, and periuterine varices were analyzed and correlated with
      symptoms of pelvic pain. CONCLUSION: Overall, TR-MRA is a useful sequence for the
      assessment of ovarian vein reflux, which may aid the evaluation of pelvic
      congestion syndrome.

PMID- 19843729
TI  - Ability to reduce the incidence of pneumothorax in transthoracic CT-guided
      biopsy.

PMID- 19843730
TI  - Partial versus partial-thickness tears of the scapholunate and lunatotriquetral
      ligaments.

PMID- 19843731
TI  - Extracolonic findings from CTC: balancing risks and benefits.

PMID- 19843732
TI  - Staging of non-small cell lung cancer using integrated PET/CT.

PMID- 19843733
TI  - Coping with war mass casualties in a hospital under fire: the radiology
      experience.
AB  - OBJECTIVE: We report the role of the imaging department at a level 1 trauma
      center during the Second Lebanon War (summer 2006). Our institution received 849
      military and civilian casualties, an average of 25 war-injured patients per day,
      338 with acute traumatic stress disorders and 511 physically injured, coming in
      waves after a rocket attack or a battle confrontation. About 12 potentially
      critical physically injured patients per day were referred to the imaging
      department for sometimes complex imaging procedures. The unpredictable waves of
      casualties and nature of the injuries forced us to reorganize our routine
      workflow to provide adequate care to casualties and to nonemergent patients. Our
      nurses' station was transformed into a small emergency department. The radiology
      staff was distributed into 12 diagnostic stations, providing 24-hour service.
      Communication was improved by means of walkie-talkies. Three ultrasound units
      were placed at the emergency department for immediate focused assessment with
      sonography for trauma performance enabling initial triage of patients. The site
      and extent of injuries were accurately diagnosed on CT and CT angiography.
      Digital angiography allowed definitive vascular diagnosis and interventional
      procedures. CONCLUSION: Adequate communication, strict workflow, and correct use
      of imaging protocols ensured optimal triage, diagnosis, and therapy of casualties
      while maintaining care for nonwar patients.

PMID- 19843734
TI  - Pulmonary embolism in pregnancy: comparison of pulmonary CT angiography and lung
      scintigraphy.
AB  - OBJECTIVE: The purpose of this study was to retrospectively compare the
      diagnostic adequacy of lung scintigraphy with that of pulmonary CT angiography
      (CTA) in the care of pregnant patients with suspected pulmonary embolism.
      MATERIALS AND METHODS: Patient characteristics, radiology report content,
      additional imaging performed, final diagnosis, and diagnostic adequacy were
      recorded for pregnant patients consecutively referred for lung scintigraphy or
      pulmonary CTA according to physician preference. Measurements of pulmonary
      arterial enhancement were performed on all pulmonary CTA images of pregnant
      patients. Lung scintigraphy and pulmonary CTA studies deemed inadequate for
      diagnosis at the time of image acquisition were further assessed, and the cause
      of diagnostic inadequacy was determined. The relative contribution of the
      inferior vena cava to the right side of the heart was measured on nondiagnostic
      CTA images and compared with that on CTA images of age-matched nonpregnant women,
      who were the controls. RESULTS: Twenty-eight pulmonary CTA examinations were
      performed on 25 pregnant patients, and 25 lung scintigraphic studies were
      performed on 25 pregnant patients. Lung scintigraphy was more frequently adequate
      for diagnosis than was pulmonary CTA (4% vs 35.7%) (p = 0.0058). Pulmonary CTA
      had a higher diagnostic inadequacy rate among pregnant than nonpregnant women
      (35.7% vs 2.1%) (p < 0.001). Transient interruption of contrast material by
      unopacified blood from the inferior vena cava was identified in eight of 10
      nondiagnostic pulmonary CTA studies. CONCLUSION: We found that lung scintigraphy
      was more reliable than pulmonary CTA in pregnant patients. Transient interruption
      of contrast material by unopacified blood from the inferior vena cava is a common
      finding at pulmonary CTA of pregnant patients.

PMID- 19843735
TI  - CT-guided core biopsy of lung lesions: a primer.
AB  - OBJECTIVE: CT-guided core biopsy is playing an increasing role in the diagnosis
      of benign disease, cellular differentiation, somatic mutation analysis, and
      molecular fingerprint analysis. CONCLUSION: In this article, we summarize the
      basic concepts, protocols, and techniques that we use for CT-guided core biopsy
      of lung lesions to assist radiologists in obtaining diagnostic specimens while
      reducing preventable complications.

PMID- 19843736
TI  - CT colonography: coming of age.
AB  - OBJECTIVE: The purpose of this article is to highlight key issues in CT
      colonography (CTC) for radiologists so they can represent the technology
      accurately to referring physicians and provide a perspective that will hopefully
      augment best care for their patients. CONCLUSION: With publication of the
      National CT Colonography Trial and the endorsement of CTC for screening by a
      multisociety task force that included the American Cancer Society, American
      College of Radiology, and U.S. Multisociety Task Force on Colorectal Cancer, the
      clinical validation of CTC has been completed, and CTC is now ready for
      widespread clinical application. Radiologists must be skilled in CTC and
      knowledgeable about colorectal cancer screening issues.

PMID- 19843737
TI  - Epiploic appendagitis: an entity frequently unknown to clinicians--diagnostic
      imaging, pitfalls, and look-alikes.
AB  - OBJECTIVE: Epiploic appendagitis is an ischemic infarction of an epiploic
      appendage caused by torsion or spontaneous thrombosis of the epiploic appendage
      central draining vein. When it occurs on the right side of the abdomen, it can
      mimic appendicitis and right-sided diverticulitis; whereas when it occurs on the
      left side of the abdomen, it is often mistaken for sigmoid diverticulitis. The
      purpose of this article is to review the diagnostic imaging of this entity.
      CONCLUSION: Epiploic appendagitis is self-limited and spontaneously resolves
      without surgery within 5-7 days. Therefore, it is imperative for radiologists to
      be familiar with this entity.

PMID- 19843738
TI  - Preliminary estimate of triphasic CT enterography performance in hemodynamically
      stable patients with suspected gastrointestinal bleeding.
AB  - OBJECTIVE: The objective of our study was to retrospectively evaluate the
      performance of triphasic CT enterography and identify causes of false-negative CT
      results in hemodynamically stable patients with suspected gastrointestinal
      bleeding. MATERIALS AND METHODS: A retrospective review of 48 patients (male
      female ratio, 22:26) with suspected gastrointestinal bleeding (first-episode
      gastrointestinal bleed, n = 19; obscure gastrointestinal bleed, n = 29) who
      underwent triphasic CT enterography was performed. All patients had endoscopic,
      pathologic, or other imaging confirmation within 3 months of triphasic CT
      enterography. The sensitivity and specificity of triphasic CT enterography were
      calculated using pathology, endoscopy, or other imaging confirmation as the
      reference standard. Results were retrospectively reviewed to determine the cause
      of missed findings at triphasic CT enterography. RESULTS: The overall sensitivity
      and specificity of triphasic CT enterography for detecting gastrointestinal
      bleeding was 33% (7/21) and 89% (24/27), respectively. Sensitivity and
      specificity were higher in first-episode gastrointestinal bleed cases (42% and
      100%, respectively) than in obscure gastrointestinal bleed cases (22% and 85%).
      In the subset of patients undergoing capsule endoscopy (n = 17), only triphasic
      CT enterography identified two of three bleeding sources. Triphasic CT
      enterography did not identify six ulcers, four vascular malformations, two
      hemorrhoids, a duodenal mass, and a bleeding colonic diverticulum. The missed
      findings at triphasic CT enterography were attributed to being CT occult (n = 9),
      perception errors (n = 4), and technical errors (n = 1). If perception errors are
      excluded, the sensitivity of triphasic CT enterography increases to 52% (11/21).
      CONCLUSION: Triphasic CT enterography can be a useful and complementary test in
      the evaluation of clinically stable patients with suspected gastrointestinal
      bleeding by identifying the bleeding source in one third to one half of patients.
      Because of the potential for perception errors, radiologists should familiarize
      themselves with the appearance of bleeding sources at CT enterography.

PMID- 19843739
TI  - Hepatic iron deposition in patients with liver disease: preliminary experience
      with breath-hold multiecho T2*-weighted sequence.
AB  - OBJECTIVE: The purpose of this study was to conduct, using histopathologic
      examination as the reference standard, a preliminary evaluation of the use of a
      breath-hold multiecho T2(*)-weighted MRI sequence in the detection and
      quantification of hepatic iron deposition in patients with liver disease.
      MATERIALS AND METHODS: The images of 43 patients with liver disease who underwent
      1.5-T MRI of the liver that included a multiecho T2(*)-weighted sequence who also
      underwent concomitant liver biopsy or liver transplantation were assessed. Two
      independent observers measured hepatic T2(*) by placing regions of interest in
      the hepatic parenchyma. Hepatic T2(*) values were compared between patients
      stratified by hepatic iron grade and were correlated with histopathologic iron
      grade. Receiver operating characteristics analysis was performed to assess the
      accuracy of images obtained with the hepatic T2(*)-weighted sequence in the
      diagnosis of iron deposition. RESULTS: Patients with iron deposition had shorter
      hepatic T2(*) values than did patients without iron deposition (mean T2(*), 17.7
      vs 32.3 milliseconds with pooled data from both observers; p < 0.0001). Patients
      with iron grade 3 or greater had shorter T2(*) values than those with iron grade
      2 or less (10.1 vs 20.8 milliseconds; p < 0.0001). There was a strong negative
      correlation between hepatic T2(*) and histopathologic iron grade (r = -0.849; p <
      0.0001). For the prediction of iron grades 1 or greater and 3 or greater, area
      under the curve, sensitivity, and specificity were 0.968-0.982, 90.5-100%, and
      100-97.3% at T2(*) cutoffs of less than 24 and less than 14 milliseconds,
      respectively. CONCLUSION: Hepatic iron overload in patients with liver disease
      can be assessed rapidly and accurately with MRI performed with a breath-hold
      T2(*)-weighted sequence.

PMID- 19843740
TI  - CT protocols for acute appendicitis: time for change.

PMID- 19843741
TI  - MDCT for suspected acute appendicitis in adults: impact of oral and IV contrast
      media at standard-dose and simulated low-dose techniques.
AB  - OBJECTIVE: The objective of this study was to prospectively investigate the
      influence of oral, IV, and oral and IV contrast media on the information provided
      by MDCT at standard and simulated low radiation doses in adults suspected of
      having acute appendicitis. SUBJECTS AND METHODS: One hundred thirty-one
      consecutive patients (80 women, 51 men; age range, 18-87 years; mean age, 37
      years) suspected of having appendicitis were randomly assigned to either ingest
      or not ingest iodinated contrast material. Thereafter, all patients underwent IV
      unenhanced and enhanced abdominopelvic MDCT with a 4 x 2.5 mm collimation at 120
      kVp and 100 mAs(eff). Dose reduction corresponding to 30 mAs(eff) was simulated.
      Two radiologists independently read scans during separate sessions, assessed
      appendix visualization, and proposed a diagnosis (i.e., appendicitis or an
      alternative diagnosis). The final diagnosis was based on either surgical findings
      or clinical follow-up. Data were analyzed by factorial analysis of multiple
      correspondences followed by an ascending hierarchic classification method.
      RESULTS: Factorial analysis and ascending hierarchic classification revealed
      that, in terms of diagnostic correctness, reader influence predominated over the
      influence of IV and oral contrast media use and radiation dose but that
      correctness was also influenced by the patient's sex (p = 0.048) and was lower in
      cases of alternative diseases (p < 0.001). Visualization of the appendix depended
      predominantly on the reader rather than on the use of IV, oral, or oral and IV
      contrast agents or on radiation dose. CONCLUSION: Diagnostic correctness is much
      more influenced by the reader than by the use of contrast medium (oral, IV, or
      both) or of simulated low-radiation-dose technique.

PMID- 19843742
TI  - Abdominal 64-MDCT for suspected appendicitis: the use of oral and IV contrast
      material versus IV contrast material only.
AB  - OBJECTIVE: The objective of our study was to compare the diagnostic accuracy of
      IV contrast-enhanced 64-MDCT with and without the use of oral contrast material
      in diagnosing appendicitis in patients with abdominal pain. MATERIALS AND
      METHODS: We conducted a randomized trial of a convenience sample of adult
      patients presenting to an urban academic emergency department with acute
      nontraumatic abdominal pain and clinical suspicion of appendicitis,
      diverticulitis, or small-bowel obstruction. Patients were enrolled between 8 am
      and 11 pm when research assistants were present. Consenting subjects were
      randomized into one of two groups: Group 1 subjects underwent 64-MDCT performed
      with oral and IV contrast media and group 2 subjects underwent 64-MDCT performed
      solely with IV contrast material. Three expert radiologists independently
      reviewed the CT examinations, evaluating for the presence of appendicitis. Each
      radiologist interpreted 202 examinations, ensuring that each examination was
      interpreted by two radiologists. Individual reader performance and a combined
      interpretation performance of the two readers assigned to each case were
      calculated. In cases of disagreement, the third reader was asked to deliver a
      tiebreaker interpretation to be used to calculate the combined reader
      performance. Final outcome was based on operative, clinical, and follow-up data.
      We compared radiologic diagnoses with clinical outcomes to calculate the
      diagnostic accuracy of CT in both groups. RESULTS: Of the 303 patients enrolled,
      151 patients (50%) were randomized to group 1 and the remaining 152 (50%) were
      randomized to group 2. The combined reader performance for the diagnosis of
      appendicitis in group 1 was a sensitivity of 100% (95% CI, 76.8-100%) and
      specificity of 97.1% (95% CI, 92.7-99.2%). The performance in group 2 was a
      sensitivity of 100% (73.5-100%) and specificity of 97.1% (92.9-99.2%).
      CONCLUSION: Patients presenting with nontraumatic abdominal pain imaged using 64
      MDCT with isotropic reformations had similar characteristics for the diagnosis of
      appendicitis when IV contrast material alone was used and when oral and IV
      contrast media were used.

PMID- 19843743
TI  - Comparison of optical colonoscopy and CT colonography for polyp detection.

PMID- 19843744
TI  - CT colonography predictably overestimates colonic length and distance to polyps
      compared with optical colonoscopy.
AB  - OBJECTIVE: The purpose of this study was to determine the discrepancy between CT
      colonography (CTC) and optical colonoscopy (OC) measurements for both anus-to
      cecum length and anus-to-polyps distance and then determine whether a conversion
      factor could be generated to equate these CTC and OC distances. MATERIALS AND
      METHODS: We retrospectively reviewed CTC and OC reports from patients who had
      undergone both procedures as part of an established protocol. The anus-to-cecum
      measurement recorded on a single proprietary CTC workstation was compared with
      the OC cecal length for each patient. Likewise, anus-to-polyp distances were
      compared as measured by the radiologist and endoscopist. RESULTS: Three hundred
      thirty-eight patients and 437 polyps were identified with complete data from both
      CTC and same-day OC. The average anus-to-cecum distance measured at CTC was 189
      cm (range, 75-257 cm) and at OC, 108 cm (range, 65-150 cm). For polyps proximal
      to the splenic flexure (n = 145), the CTC anus-to-polyp measurement was on
      average 1.7 times that measured at OC. For left-sided polyps (n = 292), the CTC
      measurement was, on average, within 12 cm or 1.3 times that of the OC anus-to
      polyp measurement. All the differences between CTC and OC measurements of cecal
      length and polyp distances were found to be statistically significant using a
      paired Student's t test of means (p < 0.001). CONCLUSION: Anus-to-cecum and anus
      to-polyp distances are disparate but comparable using a conversion factor of 0.57
      for the CTC anus-to-cecum measurement and 0.59 for right-sided CTC anus-to-polyp
      or 0.78 for left-sided CTC anus-to-polyp measurements. These anus-to-polyp
      conversion factors could potentially augment current CTC guidelines for accurate
      and precise polyp localization and removal at endoscopy.

PMID- 19843745
TI  - Normalized distance along the colon centerline: a method for correlating polyp
      location on CT colonography and optical colonoscopy.
AB  - OBJECTIVE: The ability to accurately locate a polyp found on CT colonography
      (CTC) at subsequent optical colonoscopy (OC) is an important part of the
      successful implementation of CTC for colorectal cancer screening. The purpose of
      this study was to determine whether a polyp's normalized distance along the colon
      centerline derived from CTC data can accurately predict its location on OC.
      MATERIALS AND METHODS: The polyp population consisted of 152 polyps in 121
      patients. CTC polyp findings were verified by same-day segmentally-unblinded OC.
      Each polyp's normalized distance along the colon centerline was computed by
      dividing its distance from the anorectal junction measured along the colon
      centerline by the length of the colon at CTC. The predicted polyp location at OC
      was computed by multiplying the normalized distance along the colon centerline by
      the colon length at OC (i.e., the distance to the cecum as determined at full
      colonoscope insertion). The differences between the true and predicted polyp
      locations at OC were compared using paired Student's t tests, linear regression,
      prediction interval assessment, and Bland-Altman analyses. RESULTS: The
      differences between the true and predicted polyp locations at OC using the supine
      and prone CTC-normalized distances along the colon centerline were 2.2 +/- 10.5
      cm (mean +/- SD; n = 136) and 1.5 +/- 10.5 cm (n = 135), respectively. The
      predicted location was within 10 cm of its true location for 71.3% (97/136) to
      74.8% (101/135) of polyps and within 20 cm of its true location for 93.3%
      (126/135) to 93.4% (127/136) of polyps. CONCLUSION: By computing the normalized
      distance along the colon centerline of a polyp found at CTC, the location of a
      polyp at OC can be predicted to within 10 cm (i.e., 1 colonoscope mark) for the
      majority of polyps.

PMID- 19843747
TI  - Intraabdominal complications secondary to ventriculoperitoneal shunts: CT
      findings and review of the literature.
AB  - OBJECTIVE: The purpose of our study was to evaluate the abdominopelvic CT
      findings of various intraabdominal complications secondary to
      ventriculoperitoneal shunts for hydrocephalus and to review the literature.
      MATERIALS AND METHODS: The CT images of 70 patients (33 men and 37 women; mean
      age, 48.5 years) who underwent ventriculoperitoneal shunt placement and
      abdominopelvic CT because of shunt-related abdominal symptoms were reviewed
      retrospectively. CT images were analyzed with regard to the location of the
      shunting catheter tip; site, size, wall, and septa of localized fluid collection;
      peritoneal thickening; omentomesentery infiltration; abscess; bowel perforation;
      abdominal wall infiltration; and thickening of the catheter track wall. RESULTS:
      The mean period between the last ventriculoperitoneal shunting operation and CT
      was 11 months (range, 1 week to 115 months), and the mean number of
      ventriculoperitoneal shunting operations undergone was 1.4 (range, 1-6). A total
      of 76 ventriculoperitoneal shunting catheters were introduced in 70 patients: 64
      patients had a unilateral catheter inserted and six patients had bilateral
      catheters inserted. Sixteen patients (22.9%) were pathologically diagnosed with
      ventriculoperitoneal shunt-related complications: 11 cases (15.7%) of shunt
      infection, six cases (8.6%) of CSF pseudocyst, four cases (5.7%) of abdominal
      abscess, three cases (4.3%) of infected fluid collection, and one case (1.4%) of
      bowel perforation. Microorganisms were cultured from the tip of the shunting
      catheter or peritoneal fluid in 11 patients (15.7%). CONCLUSION: On
      abdominopelvic CT, various intraabdominal complications secondary to
      ventriculoperitoneal shunt were shown, of which, shunt infection was the most
      common, followed by CSF pseudocyst, abscess, and infected fluid collection.

PMID- 19843746
TI  - Automated measurement of colorectal polyp height at CT colonography: hyperplastic
      polyps are flatter than adenomatous polyps.
AB  - OBJECTIVE: Hyperplastic polyps are more difficult to detect than adenomatous
      polyps at CT colonography (CTC), and it has been theorized that this difference
      in detectability is because hyperplastic polyps are flatter. Using automated
      software that computes polyp height, we determined whether hyperplastic colonic
      polyps on CTC are indeed flatter than adenomatous polyps of comparable width.
      MATERIALS AND METHODS: At three medical centers, 1,186 patients underwent oral
      contrast-enhanced CTC and same-day optical colonoscopy (OC) with segment
      unblinding for colorectal cancer screening. One hundred eighty-five of the
      patients had at least one hyperplastic or adenomatous polyp 6-10 mm visible at
      both OC and CTC, where size was determined by a calibrated guidewire at OC. To
      assess flatness, the heights of the polyps at CTC were measured using a validated
      automated software program. The heights and height-to-width ratios of the
      hyperplastic polyps were compared with those of the adenomatous polyps using a
      Student's t test (two-tailed, unpaired, unequal variance). RESULTS: There were
      176 adenomatous and 83 hyperplastic polyps visible at segment-unblinded OC. The
      fraction of these polyps that were measurable at CTC using the automated software
      was not significantly different for adenomatous versus hyperplastic polyps
      (158/176 [89.8%] vs 73/87 [83.9%], respectively; p = 0.2). The average height-to
      width ratios using automated width measurements were 15% less for hyperplastic
      polyps: 0.39 +/- 0.20 (n = 158) and 0.33 +/- 0.19 (n = 73) for adenomatous and
      hyperplastic polyps, respectively (p = 0.03). When polyps of comparable OC size
      or CTC width were considered, the heights of hyperplastic polyps were up to 27%
      less than those of adenomatous polyps. CONCLUSION: For 6-10 mm polyps of a given
      size as determined by OC or a given width at CTC, hyperplastic polyps tend to be
      flatter (i.e., have lower height) compared with adenomatous polyps.

PMID- 19843748
TI  - Normal dynamic MRI enhancement patterns of the upper abdominal organs: gadoxetic
      acid compared with gadobutrol.
AB  - OBJECTIVE: The purpose of this study was to investigate whether, at dynamic MRI
      of the upper abdominal organs, contrast enhancement with gadoxetic acid, a
      hepatobiliary contrast agent, is comparable with that achieved with an
      extracellular contrast agent. SUBJECTS AND METHODS: Dynamic gadoxetic acid
      enhanced MRI of the pancreas, spleen, kidney, liver, and abdominal aorta was
      performed on 50 patients; dynamic gadobutrol-enhanced MRI was performed on a
      control group of 50 patients; and the images were compared. Dynamic imaging with
      a T1-weighted volumetric interpolated breath-hold examination gradient-echo
      sequence (TR/TE, 3.35/1.35; flip angle, 12 degrees ) was performed before and 20
      (arterial phase), 55 (portal venous phase), and 90 (hepatic venous phase) seconds
      after bolus injection of gadoxetic acid (0.25 mmol/mL) or gadobutrol (1.0
      mmol/mL). Signal-to-noise ratios and enhancement indexes were calculated for each
      organ and time. RESULTS: All MR images in both groups were of diagnostic quality.
      During the early dynamic phases, significantly lower mean enhancement indexes
      were found in the gadoxetic acid group than in the gadobutrol group in the
      pancreas (portal venous phase, 0.66, 1.39, p <or= 0.001; hepatic venous phase,
      0.51, 1.36, p <or= 0.001), spleen (portal venous phase, 1.54, 2.41, p <or= 0.001;
      hepatic venous phase, 1.19, 2.23, p <or= 0.001), renal cortex (portal venous
      phase, 1.76, 2.63, p <or= 0.001; hepatic venous phase, 1.60, 2.63, p <or= 0.001),
      and liver (portal venous phase, 0.76, 0.94, p = 0.016; hepatic venous phase,
      0.76, 1.04, p <or= 0.001). In the abdominal aorta, the mean enhancement index was
      greater after bolus injection of gadoxetic acid (arterial phase, 3.33, 2.24, p
      <or= 0.005). CONCLUSION: Early dynamic MRI of the upper abdominal organs,
      especially the spleen, pancreas, and kidney, benefits from the higher gadolinium
      concentration of gadobutrol than in the organ-specific contrast agent gadoxetic
      acid. Higher protein binding resulting in increased relaxivity of gadoxetic acid
      compensates for the low gadolinium concentration in the abdominal aorta.

PMID- 19843749
TI  - The actual role of CT and ventilation-perfusion scanning in workup for suspected
      pulmonary embolism: evidence from hospitals.
AB  - OBJECTIVE: Over the past two decades, CT has been found valuable in the diagnosis
      of pulmonary embolism (PE). We sought to ascertain the relative roles of CT and
      ventilation-perfusion (V/Q) scanning, the previously preferred technique, in the
      diagnosis of PE in recent practice and whether there is variation among hospital
      types. MATERIALS AND METHODS: Using the Medicare anonymized 5% of beneficiaries
      complete claims file for 2005, we studied the use of relevant CT and V/Q scanning
      in the evaluation of patients with a diagnosis of PE and of patients with
      symptoms that might have been due to PE (chest pain, syncope, difficulty
      breathing). In 2008, we surveyed the radiology departments of Pennsylvania
      hospitals about the use of CT and V/Q scanning for PE, service availability
      hours, and what equipment was used. RESULTS: In all data, we found that CT was
      used approximately six times as frequently as V/Q scanning. In the Medicare data,
      only small differences in frequency of use of CT and V/Q scanning were associated
      with hospital characteristics. Academic hospitals did not differ in a major way
      from other hospitals, nor did small or rural hospitals. In the survey, 97% of
      radiology departments reported that CT was available for evaluation of PE 24
      hours a day 7 days a week. Ninety-three percent of departments reported V/Q
      scanning was available at some times; 77% reported V/Q available at all times.
      CONCLUSION: CT was a fully disseminated and dominant technique for the diagnosis
      of PE by 2005, and it was readily available at small and rural hospitals. The
      lack of availability of off-hours V/Q scanning at a substantial fraction of
      hospitals may be a problem for patients with contraindications to CT.

PMID- 19843750
TI  - Radiology practices' use of external off-hours teleradiology services in 2007 and
      changes since 2003.
AB  - OBJECTIVE: Our objective is to report patterns of utilization of external off
      hours teleradiology services (EOTSs) in 2007 and changes since 2003. MATERIALS
      AND METHODS: We analyzed non-individually identified data from the American
      College of Radiology's 2007 Survey of Member Radiologists and its 2003 Survey of
      Radiologists. Responses were weighted to be nationally representative of
      individual radiologists and radiology practices. We present descriptive
      statistics and multivariable regression analysis results on the use of EOTSs in
      2007 and comparisons with 2003. RESULTS: Overall, 44% of all radiology practices
      in the United States reported using EOTSs in 2007. These practices included 45%
      of all U.S. radiologists. Out-of-practice teleradiology had been used by 15% of
      practices in 2003. Regression analysis indicates that, other practice
      characteristics being equal, in 2007, primarily academic practices had lower odds
      of using EOTSs than private radiology practices. Also, large practices (>or= 30
      radiologists) had lower odds of using EOTSs than practices with 15-29
      radiologists. Small practices (1-10 radiologists) had high odds, but
      nonmetropolitan practices did not. There were no significant differences by
      geographic region of the United States. CONCLUSION: Use of EOTSs was widespread
      by 2007, and it had been increasing rapidly in the preceding few years. Patterns
      of use were generally as might be expected except that nonmetropolitan practices
      did not have high odds of using EOTSs.

PMID- 19843752
TI  - Rheumatoid arthritis and tuberculous arthritis: differentiating MRI features.
AB  - OBJECTIVE: The purpose of our study was to determine the MRI findings of
      rheumatoid arthritis (RA) and tuberculous arthritis, with emphasis on
      differential diagnostic features. MATERIALS AND METHODS: MR images of 63 joints
      in 62 patients with clinically or pathologically proven RA (36 joints in 35
      patients) or tuberculous arthritis (27 joints in 27 patients) were evaluated
      retrospectively with regard to pattern and degree of synovial thickening, size of
      bone erosions, rim enhancement at bone erosions, degree of bone marrow and
      periarticular soft-tissue edema, and presence and number of extraarticular cystic
      masses. MRI findings were compared between RA and tuberculous arthritis by
      statistical analysis using kappa statistics, the Mann-Whitney U test, linear-by
      linear association, and the chi-square test. RESULTS: Nonuniform and greater
      degree of synovial thickening was more frequent in RA (p < 0.01); the thicker the
      synovial membrane, the greater the likelihood of RA (p < 0.01). Bone erosions of
      tuberculous arthritis were larger (p < 0.01), and the likelihood of tuberculous
      arthritis increased proportionally to the increment of size of the bone erosions
      (p < 0.01). Rim enhancement at bone erosion was more frequent in tuberculous
      arthritis (p < 0.01). Extraarticular cystic masses were more frequently seen and
      more numerous in tuberculous arthritis (p < 0.01). CONCLUSION: Uniform synovial
      thickening, large size of bone erosion, rim enhancement at site of bone erosion,
      and extraarticular cystic masses were more frequent and more numerous in
      tuberculous arthritis. MRI may be helpful in the differentiation between RA and
      tuberculous arthritis.

PMID- 19843751
TI  - Dose to radiosensitive organs during routine chest CT: effects of tube current
      modulation.
AB  - OBJECTIVE: The aims of this study were to estimate the dose to radiosensitive
      organs (glandular breast and lung) in patients of various sizes undergoing
      routine chest CT examinations with and without tube current modulation; to
      quantify the effect of tube current modulation on organ dose; and to investigate
      the relation between patient size and organ dose to breast and lung resulting
      from chest CT examinations. MATERIALS AND METHODS: Thirty voxelized models
      generated from images of patients were extended to include lung contours and were
      used to represent a cohort of women of various sizes. Monte Carlo simulation
      based virtual MDCT scanners had been used in a previous study to estimate breast
      dose from simulations of a fixed-tube-current and a tube current-modulated chest
      CT examinations of each patient model. In this study, lung doses were estimated
      for each simulated examination, and the percentage organ dose reduction
      attributed to tube current modulation was correlated with patient size for both
      glandular breast and lung tissues. RESULTS: The average radiation dose to lung
      tissue from a chest CT scan obtained with fixed tube current was 23 mGy. The use
      of tube current modulation reduced the lung dose an average of 16%. Reductions in
      organ dose (up to 56% for lung) due to tube current modulation were more
      substantial among smaller patients than larger. For some larger patients, use of
      tube current modulation for chest CT resulted in an increase in organ dose to the
      lung as high as 33%. For chest CT, lung dose and breast dose estimates had
      similar correlations with patient size. On average the two organs receive
      approximately the same dose effects from tube current modulation. CONCLUSION: The
      dose to radiosensitive organs during fixed-tube-current and tube current
      modulated chest CT can be estimated on the basis of patient size. Organ dose
      generally decreases with the use of tube current-modulated acquisition, but
      patient size can directly affect the dose reduction achieved.

PMID- 19843753
TI  - Postoperative MDCT of tibial plateau fractures.
AB  - OBJECTIVE: The purposes of this retrospective study were to elaborate our
      experience in postoperative MDCT of tibial plateau fractures, to establish the
      frequency of these fractures and the indications for MDCT, and to assess the
      common findings and their clinical importance. MATERIALS AND METHODS: A total of
      782 knee injuries were imaged with MDCT at a level 1 trauma center over 86
      months. A total of 592 knees had a tibial plateau fracture; 381 of these
      fractures were managed surgically, and postoperative MDCT was performed on 36 of
      these knees (9%). At postoperative image analysis, an orthopedic surgeon
      evaluated reduction as good or suboptimal using the first postoperative
      radiographs. Fracture healing was determined as complete ossification, partial
      ossification, or nonunion on MDCT images acquired later in follow-up. The MDCT
      findings were compared with the radiographic findings to assess the usefulness
      and clinical importance of MDCT. RESULTS: The main indications for MDCT were
      assessment and follow-up of the joint articular surface and evaluation of
      fracture healing. Orthopedic hardware caused no diagnostic problems at MDCT.
      Postoperative MDCT revealed additional clinically important information on 29
      patients (81%), and 14 patients (39%) underwent reoperation. CONCLUSION:
      Postoperative MDCT of tibial plateau fractures is performed infrequently, even in
      a large trauma center. When it is performed, however, because of suspicion of
      increasing articular step-off or fracture nonunion, postoperative MDCT reveals
      clinically significant information in most cases.

PMID- 19843754
TI  - Patella alta: lack of correlation between patellotrochlear cartilage congruence
      and commonly used patellar height ratios.
AB  - OBJECTIVE: The purposes of this study were to assess the degree of
      patellotrochlear chondral overlap (patellotrochlear index), correlate it with the
      Insall-Salvati and modified Insall-Salvati indexes, and determine the association
      between these measurements and patellofemoral chondral defects. MATERIALS AND
      METHODS: Sagittal 1.5-T and 3-T MR images of 100 consecutively registered
      patients with symptoms were analyzed, and the Insall-Salvati index, modified
      Insall-Salvati index, patellotrochlear index, and patellophyseal index (ratio of
      the height of patella above the physeal line to the length of the patellar
      articular cartilage) were calculated. The upper and lower limits of 2 SDs were
      used to define patella alta and baja, and the correlation coefficient curves were
      plotted to compare techniques. The indexes in normal knees were compared with
      those in knees with severe chondral defects. RESULTS: The mean patellotrochlear
      index was 0.49 +/- 0.15 (SD) (range, 0-0.88). On the basis of calculation of 2
      SDs, patella alta was determined to have a patellotrochlear index less than 0.18
      and patella baja, an index greater than 0.80. Weak correlation was found between
      the measured patellotrochlear index and Insall-Salvati index (r = -0.224) and
      between the patellotrochlear index and modified Insall-Salvati index (r = 
      0.073). A strong correlation was found between the patellotrochlear index and
      patellophyseal index (r = -0.813). A statistically significant (p < 0.05)
      difference in the modified Insall-Salvati index and patellophyseal index was
      found between knees with normal and those with severe cartilage defects.
      CONCLUSION: Our results indicate that the commonly used Insall-Salvati and
      modified Insall-Salvati indexes do not correlate with patellotrochlear articular
      cartilage congruence. We did find an association between the modified Insall
      Salvati and patellophyseal indexes and the presence of severe chondral defects.

PMID- 19843755
TI  - Degeneration of the long biceps tendon: comparison of MRI with gross anatomy and
      histology.
AB  - OBJECTIVE: The objective of our study was to relate alterations in biceps tendon
      diameter and signal on MR images to gross anatomy and histology. MATERIALS AND
      METHODS: T1-weighted, T2-weighted fat-saturated, and proton density-weighted fat
      saturated spin-echo sequences were acquired in 15 cadaveric shoulders. Biceps
      tendon diameter (normal, flattened, thickened, and partially or completely torn)
      and signal intensity (compared with bone, fat, muscle, and joint fluid) were
      graded by two readers independently and in a blinded fashion. The distance of
      tendon abnormalities from the attachment at the glenoid were noted in
      millimeters. MRI findings were related to gross anatomic and histologic findings.
      RESULTS: On the basis of gross anatomy, there were six normal, five flattened,
      two thickened, and two partially torn tendons. Reader 1 graded nine diameter
      changes correctly, missed two, and incorrectly graded four. The corresponding
      values for reader 2 were seven, one, and five, respectively, with kappa = 0.75.
      Histology showed mucoid degeneration (n = 13), lipoid degeneration (n = 7), and
      fatty infiltration (n = 6). At least one type of abnormality was found in each
      single tendon. Mucoid degeneration was hyperintense compared with fatty
      infiltration on T2-weighted fat-saturated images and hyperintense compared with
      magic-angle artifacts on proton density-weighted fat-saturated images. MRI-based
      localization of degeneration agreed well with histologic findings. CONCLUSION:
      Diameter changes are specific but not sensitive in diagnosing tendinopathy of the
      biceps tendon. Increased tendon signal is most typical for mucoid degeneration
      but should be used with care as a sign of tendon degeneration.

PMID- 19843756
TI  - MDCT arthrography features of ulnocarpal impaction syndrome.
AB  - OBJECTIVE: The aim of this article is to present the imaging patterns of
      ulnocarpal impaction syndrome (Palmer class II lesions) on MDCT arthrography.
      CONCLUSION: MDCT arthrography is an excellent tool for imaging patients with
      clinically suspected ulnocarpal impaction syndrome, allowing identification of
      the spectrum of findings and proper classification according to Palmer class II
      (degenerative) lesions, which directly affects management.

PMID- 19843757
TI  - Water diffusivity: comparison of primary CNS lymphoma and astrocytic tumor
      infiltrating the corpus callosum.
AB  - OBJECTIVE: The purpose of this study was to determine whether lymphoma and
      astrocytic tumor infiltrating the corpus callosum can be reliably differentiated
      with measurement of water diffusivity. MATERIALS AND METHODS: Echo-planar
      diffusion-weighted MR images of 27 patients with glioblastoma multiforme, five
      patients with low-grade astrocytoma, five patients with gliomatosis cerebri, and
      nine patients with primary lymphoma infiltrating the corpus callosum were
      reviewed retrospectively. Regions of interest were drawn on apparent diffusion
      coefficient (ADC) maps inside the callosal tumor. ADCs were normalized by
      calculation of the ratio between the ADC of the tumor and the ADC of an
      uninvolved region of corpus callosum. RESULTS: The mean ADC of glioblastoma
      multiforme was 1.13 +/- 0.31 (SD) x 10(-3) mm(2)/s, and the mean tumor to corpus
      callosum ADC ratio was 1.51 +/- 0.46; of low-grade astrocytoma, 1.14 +/- 0.23 x
      10(-3) mm(2)/s and 1.54 +/- 0.28; gliomatosis cerebri, 1.01 +/- 0.20 x 10(-3)
      mm(2)/s and 1.31 +/- 0.36; and lymphoma, 0.71 +/- 0.13 x 10(-3) mm(2)/s and 0.93
      +/- 0.19. The difference between the mean tumor to corpus callosum ADC ratio of
      lymphoma and that of all grades of astrocytoma (1.48 +/- 0.43) was statistically
      significant (p < 0.001). The optimal ADC threshold for discriminating astrocytic
      tumor and lymphoma was 0.90 x 10(-3) mm(2)/s (sensitivity, 84%; specificity,
      89%). The optimal threshold for tumor to corpus callosum ADC ratio was 1.22
      (sensitivity, 73%; specificity, 100%). CONCLUSION: The water diffusivity and the
      ADC ratio of the tumor to normal-appearing corpus callosum of astrocytic tumor
      differ significantly from those of lymphoma infiltrating the corpus callosum,
      allowing reliable differentiation of the two types of tumor.

PMID- 19843758
TI  - Evaluation of the C1-C2 articulation on MDCT in healthy children and young
      adults.
AB  - OBJECTIVE: We aimed to establish normal values on MDCT images for the
      atlantoaxial relationships including the atlantoaxial interval and lateral
      atlantodens interval (ADI) that could be used to detect atlantoaxial ligamentous
      injuries in adults and children. MATERIALS AND METHODS: One hundred seventy-eight
      healthy adult patients between 20 and 40 years old and 112 pediatric patients
      between 2 months and 10 years old underwent cervical spine MDCT with multiplanar
      reconstructions. The width of the joint space between the lateral mass of C1 and
      the lateral mass of C2 was measured at three equidistant points on both the left
      and right sides on coronal reformatted images to determine the atlantoaxial
      interval. The distance between the lateral surface of the dens and the medial
      surface of the lateral mass of C1 was measured in the coronal plane to determine
      the lateral ADI bilaterally. RESULTS: The upper limit of the normal range of
      values for the atlantoaxial interval in adults was 3.34 mm on the right and 3.39
      mm on the left. The upper limit of normal for the lateral ADI was 4.67 mm on the
      right and 5.6 mm on the left. More than 95% of the pediatric population was found
      to have an atlantoaxial interval of less than 3.9 mm on either side, a right
      lateral ADI of less than 7.4 mm, and a left lateral ADI of less than 8.0 mm.
      CONCLUSION: We propose that the obtained normal values be considered as the upper
      limits of the normal range for the atlantoaxial interval in adult and pediatric
      populations on MDCT images.

PMID- 19843759
TI  - MRI of Legg-Calve-Perthes disease.
AB  - OBJECTIVE: Legg-Calve-Perthes disease is a common cause of hip pain in children
      that may be initially clinically and radiographically difficult to diagnose and
      stage. The purpose of this article is to describe and illustrate the various MRI
      appearances of this condition. CONCLUSION: MRI may show proximal femoral
      abnormalities before radiography in the setting of Legg-Calve-Perthes disease,
      allowing appropriate diagnosis and prompt treatment. MRI can also assess for
      revascularization, healing, and multiple complications.

PMID- 19843760
TI  - Radiographic predictors of disease severity in neonates and infants with
      necrotizing enterocolitis.
AB  - OBJECTIVE: The objective of our study was to validate a radiographic scale, the
      Duke abdominal assessment scale (DAAS), as a tool for predicting the severity of
      disease in neonates and infants with suspected necrotizing enterocolitis (NEC).
      MATERIALS AND METHODS: Study group patients (n = 43) underwent at least two two
      view abdominal radiographic series within 48 hours of surgical intervention for
      suspected NEC complications. Control group patients (n = 86) were patients with
      suspected NEC who did not undergo surgery for suspected NEC complications. DAAS
      scores were assigned by two pediatric radiologists with 20 and 6 years'
      experience. RESULTS: The initial radiographs of 26 of 43 (60.5%) patients in the
      study group showed fixed bowel loops (10/43, 23.3%), highly probable or definite
      pneumatosis (9/43, 20.9%), or portal venous gas (7/43, 16.3%). These findings had
      progressed to pneumoperitoneum on the follow-up series in 20 (46.5%) study group
      patients. Among the control group, three patients (3.5%) had highly probable or
      definite pneumatosis, and none had fixed bowel loops, portal venous gas, or
      pneumoperitoneum. Patients with higher DAAS scores were more likely to undergo
      surgical intervention than patients with lower scores (odds ratio, 1.69; 95% CI,
      1.40-2.03). A receiver operating characteristic curve analysis showed good
      overall performance (c statistic = 0.83) for predicting eventual surgical
      intervention in the study group with higher DAAS scores. CONCLUSION: The DAAS
      provides a standardized 10-point radiographic scale that increases with disease
      severity when using need for surgical intervention as a surrogate for severe NEC.
      For every 1-point increase in the DAAS score, patients were statistically
      significantly more likely to have severe disease as measured by need for surgical
      intervention.

PMID- 19843761
TI  - Motion artifact on high-resolution CT images of pediatric patients: comparison of
      volumetric and axial CT methods.
AB  - OBJECTIVE: The purpose of this study was to address the controversy whether the
      quality of volumetric high-resolution CT (HRCT) images is as good as that of
      axial nonvolumetric HRCT images by assessing the degree of motion artifact on
      images acquired with the two methods at MDCT of pediatric patients with known or
      suspected lung disease. MATERIALS AND METHODS: A search of the hospital
      information system was conducted to identify the cases of pediatric patients with
      clinically suspected or known interstitial lung disease who underwent 16-MDCT of
      the chest with both volumetric and axial HRCT acquisitions (both 1.25-mm slice
      thickness) from March 2005 to July 2008. Two pediatric radiologists reviewed the
      images for the presence of motion artifacts at three anatomic levels (upper,
      middle, and lower lung zones). Motion artifacts were given numerical grades
      representing no artifact to severe artifact, and the paired Student's t test was
      used to compare the scores for the two acquisition methods. A total motion score
      for each acquisition was calculated by summing the scores for each of the three
      lung zones, and the scores for the two imaging methods were compared. Correlation
      between degree of motion artifact and age was evaluated. Effective radiation
      doses were estimated for volumetric and axial CT acquisitions. RESULTS: The study
      population consisted of 54 children (28 boys, 26 girls; mean age, 11.7 +/- 3.8
      years; range, 5-18 years; eight inpatients, 46 outpatients) who underwent a total
      of 54 MDCT chest studies with volumetric and axial HRCT acquisitions. Motion
      artifact scores were higher for axial than for volumetric HRCT images of the
      upper (1.2 vs 1.0), middle (1.6 vs 1.2), and lower (2.2 vs 1.5) lung zones (p <
      0.05 at each level). The total motion score of the axial HRCT images (mean, 5;
      range, 1-9) was higher than that of the volumetric HRCT images (mean, 3.6; range,
      1-8) (p < 0.05). Younger age correlated with higher motion artifact score on
      axial HRCT images (r = -0.36, p < 0.01), whereas no correlation was found between
      age and motion artifact score on volumetric HRCT images (r = -0.12, p = 0.38).
      The effective radiation doses were 0.57 mSv for axial HRCT acquisition and 7.6
      mSv for volumetric acquisition. The addition of axial acquisition increased the
      total radiation dose of the MDCT examination 7.1%. CONCLUSION: At CT of pediatric
      patients, reconstructed HRCT images from volumetric MDCT acquisition have
      significantly less motion artifact than images obtained with traditional axial
      acquisition.

PMID- 19843762
TI  - Inflammatory myofibroblastic tumors of the abdomen as mimickers of malignancy:
      imaging features in nine children.
AB  - OBJECTIVE: The purpose of this study was to evaluate retrospectively the CT and
      sonographic features in nine children with pathologically proven inflammatory
      myofibroblastic tumors of the abdomen. CONCLUSION: Although inflammatory
      myofibroblastic tumors occur in various sites and the imaging characteristics are
      variable, tumors showed different imaging patterns that were dependent on the
      site at which the tumor had originated.

PMID- 19843763
TI  - Imaging arteriovenous fistulas.
AB  - OBJECTIVE: Arteriovenous fistulas (AVFs) are abnormal communications with
      shunting of blood from an artery to a vein. AVFs mainly involve the peripheral
      vascular system but can affect virtually any organ or system in the body. They
      may be congenital, created surgically for hemodialysis, or caused by pathologic
      processes. This review describes the diverse origins of AVFs and illustrates the
      spectrum of imaging findings at radiography, ultrasound, CT, MRI, and digital
      angiography for AVFs in different locations: the CNS, thorax, abdomen,
      musculoskeletal system, and peripheral vascular system. We also discuss syndromes
      associated with AVFs and describe recent interventional techniques for treating
      AVFs. CONCLUSION: Familiarity with the spectrum of imaging findings in AVFs is
      essential for the accurate interpretation of images and facilitates diagnosis and
      therapeutic management. Radiologists can play a critical role in the diagnosis
      and treatment of AVFs. Digital angiography is helpful in elaborating a vascular
      map for endovascular treatment.

PMID- 19843764
TI  - Color Doppler imaging evaluation of proximal vertebral artery stenosis.
AB  - OBJECTIVE: The sonographic diagnostic criteria for vertebral artery stenosis have
      not been fully investigated. The purpose of this study was to assess hemodynamic
      parameters at color Doppler imaging and to determine, with digital subtraction
      angiography as the reference standard, the optimal thresholds for evaluation of
      proximal vertebral artery stenosis. MATERIALS AND METHODS: Among 653 patients
      with symptoms of ischemia of the posterior circulation, 247 subjects with normal
      arteries or stenosis of the proximal vertebral artery confirmed with digital
      subtraction angiography were included in the study. Peak systolic velocity at the
      origin of the vertebral artery (PSV(origin)) and in intervertebral segments of
      the vertebral artery (PSV(IV)), end-diastolic velocity at the origin and in the
      intervertebral segments of the vertebral artery, and the diameter of the vascular
      lumen were measured. The cutoff values for the diagnosis of < 50%, 50-69%, and 70
      99% stenosis were determined with receiver operating characteristics analysis.
      RESULTS: The optimal cutoff values of hemodynamic parameters in evaluation of
      stenosis of the proximal vertebral artery for < 50% stenosis were PSV(origin)
      >or= 85 cm/s, PSV(origin) / PSV(IV) >or= 1.3, and end-diastolic velocity at the
      origin >or= 27 cm/s; for 50-69% stenosis were PSV(origin) >or= 140 cm/s,
      PSV(origin) / PSV(IV) >or/= 2.1, and end-diastolic velocity at the origin >or= 35
      cm/s; and for 70-99% stenosis were PSV(origin) >or= 210 cm/s, PSV(origin) /
      PSV(IV) >or= 4.0, and end-diastolic velocity at the origin >or= 50 cm/s.
      PSV(origin) was the most useful hemodynamic parameter, having accuracy of 94.5%,
      96.2%, and 88.7% for the diagnosis of < 50%, 50-69%, and 70-99% stenosis.
      CONCLUSION: Color Doppler imaging is a reliable method for evaluation of
      vertebral artery stenosis. The results derived from this study can be used as a
      reference for establishing sonographic criteria for proximal vertebral artery
      stenosis.

PMID- 19843765
TI  - MDCT angiography of mesenteric bypass surgery for the treatment of chronic
      mesenteric ischemia.
AB  - OBJECTIVE: Chronic mesenteric ischemia (CMI) is a serious condition that requires
      surgical or endovascular intervention. Surgical revascularization for the
      treatment of CMI uses different operative techniques including endarterectomy,
      vessel reimplantation, and mesenteric bypass. A basic understanding of the
      operative techniques is essential for the adequate interpretation of imaging
      studies in patients who have undergone surgery for CMI. In this article, we
      review the different operative techniques used in the treatment of CMI, discuss
      the results of surgical intervention for CMI, and illustrate how MDCT angiography
      (MDCTA) can be used for follow-up and for the detection of early and late
      complications after surgery. CONCLUSION: MDCTA is a powerful tool for the
      postoperative evaluation of patients with CMI. Early detection of graft
      dysfunction is critical to prevent graft occlusion and the development of
      potentially fatal mesenteric ischemia. MDCTA can detect early and late
      complications after surgery and guide additional surgical or endovascular
      interventions.

PMID- 19843766
TI  - Venous Doppler sonography of the extremities: a window to pathology of the
      thorax, abdomen, and pelvis.
AB  - OBJECTIVE: Swelling of an extremity may be a sign of peripheral deep venous
      thrombosis but may occasionally be due to more proximal or central venous
      obstruction. Venous Doppler sonography of the extremities is a commonly performed
      procedure to evaluate for the presence of deep venous thrombosis. Pulsed-wave
      Doppler sonography is performed as part of this procedure to evaluate for the
      presence of cardiac pulsatility or respiratory phasicity. The importance of
      information provided by the pulsed-wave Doppler waveform must not be undervalued.
      Thus, the purpose of this article is to discuss the pathology of the thorax,
      abdomen, and pelvis that can be discovered by identifying abnormal waveforms in
      the veins of the extremities. CONCLUSION: Abnormal waveforms provide information
      for compression or obstruction of the proximal venous system in the thorax,
      abdomen, and pelvis. When these waveforms are abnormal, previous imaging should
      be reviewed or additional imaging performed to discover the cause.

PMID- 19843767
TI  - Prenatal clinic.

PMID- 19843768
TI  - Rare complications and national databases.

PMID- 19843769
TI  - Sellick's maneuver: to do or not do.

PMID- 19843770
TI  - On cricoid pressure: "may the force be with you".

PMID- 19843771
TI  - Levosimendan in early sepsis: when good ideas give poor results.

PMID- 19843772
TI  - Neuraxial anesthesia for cesarean delivery: what criteria define the "optimal"
      technique?

PMID- 19843773
TI  - The poppies of Afghanistan.

PMID- 19843774
TI  - Anesthesia and pharmacogenomics: not ready for prime time.

PMID- 19843775
TI  - Craniotomy pain: trying to do better.

PMID- 19843776
TI  - A randomized clinical trial investigating the relationship between aprotinin and
      hypercoagulability in off-pump coronary surgery.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery is associated with a
      hypercoagulable state in which the platelet thrombin receptor, protease-activated
      receptor-1 (PAR-1), helps propagate a thrombin burst within saphenous vein
      grafts. Aprotinin, used in cardiothoracic surgery mainly for its antifibrinolytic
      properties, also spares platelet PAR-1 activation due to thrombin. We
      hypothesized that this PAR-1 antagonistic property provides an antithrombotic
      benefit during OPCAB surgery. METHODS: Patients were randomly assigned to receive
      saline (n = 38) or a modified full-dose regimen of aprotinin (n = 37) IV during
      OPCAB surgery. Blood sampled perioperatively from the coronary sinus, skin
      wounds, and systemic circulation was analyzed to test coagulation and platelet
      function. Major adverse cardiovascular events were monitored by obtaining
      troponin I at 24 h (myocardial infarction), predischarge computed tomography
      angiography (vein graft thrombosis), and by clinical examination for stroke.
      RESULTS: Coronary sinus blood obtained immediately after OPCAB surgery showed
      significantly less activation in the aprotinin group, as judged by reduced
      formation of platelet-leukocyte conjugates (P < 0.02) and platelet-derived
      microparticles (P < 0.05). The aprotinin group showed inhibition of platelet
      aggregation induced by thrombin (P = 0.007) but not adenosine diphosphate.
      Thrombin generation, defined by F1.2 levels, was significantly reduced by
      aprotinin in the coronary sinus but not in skin wound incisions. Major adverse
      cardiovascular events were significantly reduced in aprotinin-treated patients
      (5.4% vs 29.7%, P < 0.05). Aprotinin also demonstrated antifibrinolytic
      properties through diminished red blood cell transfusion (P < 0.04) and reduced
      blood loss postoperatively (603 +/- 330 vs 810 +/- 415 mL, P < 0.004).
      CONCLUSION: This study demonstrates that aprotinin protects patients undergoing
      OPCAB surgery from a hypercoagulable state by diminishing thrombin-induced
      platelet activation and thrombin generation within saphenous vein grafts, while
      maintaining systemic hemostatic and antifibrinolytic benefits. These results
      support further investigation of aprotinin and other PAR-1 antagonists in OPCAB
      surgery.

PMID- 19843777
TI  - Acute methadone treatment reduces myocardial infarct size via the delta-opioid
      receptor in rats during reperfusion.
AB  - BACKGROUND: Methadone is an opioid agonist often given to manage acute and
      chronic pain. We sought to determine whether methadone compared with morphine
      dose dependently reduces myocardial infarct size (IS) and whether the mechanism
      is delta-opioid receptor mediated. Furthermore, we examined whether myocardial IS
      reduction varies with the timing of methadone administration or duration of
      induced ischemia. METHODS: After surgical instrumentation, we divided male
      Sprague-Dawley rats into 3 sets. The first set was divided into groups, which
      received methadone (0.03-3 mg/kg), morphine (0.03-3 mg/kg), or water (placebo) 30
      min before ischemia. Some animals of the first set also received the delta-opioid
      antagonist naltrindole (5 mg/kg) before methadone (0.3 mg/kg), morphine (0.3
      mg/kg), or placebo administration. The second set of animals was divided into
      groups that received methadone (0.3 mg/kg) 5 min before reperfusion or 10 s after
      reperfusion. These 2 sets of animals were subjected to 30 min of myocardial
      ischemia by left anterior descending coronary artery occlusion and then 2 h of
      reperfusion. The third set of animals received placebo, methadone (0.3 mg/kg), or
      morphine (0.3 mg/kg) 5 min before reperfusion and were subjected to 45 min of
      ischemia by left anterior descending coronary artery occlusion with 2 h of
      reperfusion. Myocardial IS was assessed by staining myocardial tissue with
      triphenyltetrazolium chloride and expressed as a percentage of the area at risk
      (mean +/- sem). RESULTS: Methadone or morphine administered before ischemia
      reduced myocardial IS. The greatest effect was achieved at a dose of 0.3 mg/kg
      (methadone, 46% +/- 1%, P < 0.001 and morphine, 47% +/- 1%, P < 0.001 versus
      placebo, 61% +/- 1%, respectively). Naltrindole (5 mg/kg) blocked methadone
      induced (0.3 mg/kg) and morphine-induced (0.3 mg/kg) cardioprotection
      (naltrindole + methadone, 58% +/- 1%, P < 0.001 versus methadone; and naltrindole
      + morphine, 58 +/- 1%, P < 0.001 versus morphine). Methadone (0.3 mg/kg) reduced
      myocardial IS when given 5 min before reperfusion (46% +/- 1%, P < 0.001 versus
      placebo) but not 10 s after reperfusion (60% +/- 1%, P = 0.675 versus placebo).
      No significant myocardial IS differences were seen for placebo when comparing the
      45-min ischemia group (64% +/- 1%) with the 30-min ischemia group (60% +/- 1%, P
      = 0.069). The longer ischemia time of 45 min abrogated methadone-induced IS
      reduction (64% +/- 2%, P = 0.867 versus 45-min ischemia placebo group) and
      morphine-induced IS reduction (65% +/- 1%, P = 0.836 versus 45-min ischemia
      placebo group). CONCLUSIONS: These findings demonstrate that methadone and
      morphine produce similar myocardial IS-sparing effects that are delta-opioid
      receptor mediated and that are dependent on the duration of myocardial ischemia.

PMID- 19843779
TI  - Left atrial dissection associated with pulmonary vein cannulation.

PMID- 19843778
TI  - The interrelationship between preoperative anemia and N-terminal pro-B-type
      natriuretic peptide: the effect on predicting postoperative cardiac outcome in
      vascular surgery patients.
AB  - INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts
      adverse cardiac outcome in patients undergoing vascular surgery. However, several
      conditions might influence this prognostic value, including anemia. In this
      study, we evaluated whether anemia confounds the prognostic value of NT-proBNP
      for predicting cardiac events in patients undergoing vascular surgery. METHODS: A
      detailed cardiac history, resting echocardiography, and hemoglobin and NT-proBNP
      levels were obtained in 666 patients before vascular surgery. Anemia was defined
      as serum hemoglobin <13 g/dL for men and <12 g/dL for women. Troponin T
      measurements and 12-lead electrocardiograms were performed on postoperative days
      1, 3, 7, and 30 and whenever clinically indicated. The primary end point of the
      study was the composite of 30-day postoperative cardiovascular death, nonfatal
      myocardial infarction, and troponin T release. Receiver operating characteristic
      curve analysis was used to assess the optimal cutoff value of NT-proBNP for the
      prediction of the composite end point. Multivariable regression analysis was used
      to assess the additional value of NT-proBNP for the prediction of postoperative
      cardiac events in nonanemic and anemic patients. RESULTS: Anemia was present in
      206 patients (31%) before surgery. Hemoglobin level was inversely related with
      the NT-proBNP levels (beta coefficient = -2.242; P = 0.025). The optimal
      predictive cutoff value of NT-proBNP for predicting the composite cardiovascular
      outcome was 350 pg/mL. After adjustment for clinical cardiac risk factors, both
      anemia (odds ratio [OR] 1.53; 95% confidence interval [CI]: 1.07-2.99) and
      increased levels of NT-proBNP (OR 4.09; 95% CI: 2.19-7.64) remained independent
      predictors for postoperative cardiac events. However, increased levels of NT
      proBNP were not predictive for the risk of adverse cardiac events in the subgroup
      of anemic patients (OR 2.16; 95% CI: 0.90-5.21). CONCLUSIONS: Both anemia and NT
      proBNP are independently associated with an increased risk for postoperative
      cardiac events in patients undergoing vascular surgery. NT-proBNP has less
      predictive value in anemic patients.

PMID- 19843780
TI  - Transesophageal echocardiography to redirect the intraoperative surgical approach
      for vena cava tumor resection.

PMID- 19843781
TI  - Transesophageal echocardiography is useful for an intraoperative diagnosis of
      pulmonary artery catheter entrapment.

PMID- 19843782
TI  - Lower bispectral index values in children who are intellectually disabled.
AB  - BACKGROUND: Very few data are available on the use of bispectral index (BIS)
      monitoring in children who are intellectually disabled. Epileptiform
      electroencephalogram activity, underlying cerebral pathology, or
      anticonvulsant/spasmolytic therapy might influence BIS monitoring. Our aim in
      this exploratory study was to first compare BIS values at 4 different stages of
      anesthesia between intellectually disabled children and controls. Our second aim
      was to investigate the discriminative properties of BIS between consciousness and
      unconsciousness for intellectually disabled children and for controls. METHODS:
      Eighteen intellectually disabled children and 35 control children, aged 2-13 yr,
      were included. BIS values, landmark events, and standard monitoring values of
      vital functions were recorded throughout the whole procedure. The performance of
      BIS in distinguishing between a conscious and unconscious state was assessed from
      receiver operating characteristic curves. RESULTS: Median (interquartile range)
      BIS values for the intellectually disabled group were significantly lower than
      those for controls in the awake state (72 [48-77] vs 97 [84-98], P < 0.001),
      during stable intraoperative anesthesia (34 [21-45] vs 43 [33-52], P = 0.02), and
      during return of consciousness (59 [36-68] vs 73 [64-78], P = 0.009). The
      discriminative properties of the BIS monitor for the state of consciousness were
      comparable between the 2 groups according to the receiver operating
      characteristic curves. Nevertheless, the optimal cutoff BIS value for
      discrimination between conscious and unconscious state was 28 points lower for
      the intellectually disabled group. CONCLUSIONS: We advise anesthesiologists to be
      alert to possible lower BIS values in intellectually disabled children. There is
      a risk that they will inadvertently misinterpret the state of consciousness in
      intellectually disabled children. New multicenter studies must find the optimal
      manner of evaluating (un)consciousness in intellectually disabled patients with
      documented and confirmed specific etiologies of their intellectual disability.

PMID- 19843783
TI  - Low-dose 3 mg levobupivacaine plus 10 microg fentanyl selective spinal anesthesia
      for gynecological outpatient laparoscopy.
AB  - BACKGROUND: Lidocaine selective spinal anesthesia has been effective for short
      duration gynecological outpatient laparoscopy. We compared the intraoperative
      effectiveness, anesthetic recovery times, and patient satisfaction after
      levobupivacaine-fentanyl versus lidocaine-fentanyl spinal anesthesia during short
      duration gynecological laparoscopy. METHODS: In this double-blind study, 52
      healthy women scheduled to undergo tubal sterilization were randomly assigned to
      receive either intrathecal 10 mg lidocaine 2% plus 10 microg fentanyl (Group I)
      or intrathecal 3 mg levobupivacaine 0.5% plus 10 microg fentanyl (Group II), each
      solution made to a total volume of 3 mL with sterile water. The following
      variables were monitored intraoperatively: anesthesia onset time, need for
      anesthesia-analgesia supplementation, depth of sedation, surgical conditions, and
      occurrence of hemodynamic events. After surgery, motor block, proprioception,
      vibration sense, light touch, and Romberg's test were performed to evaluate
      whether the patients could bypass the postanesthesia care unit and be allowed to
      walk by themselves. Sensory block level was determined at 5, 10, and 15 min after
      anesthetic injection, and then every 15 min until resolution was complete. A
      difference of 25 min in sensory block resolution time was considered clinically
      relevant. RESULTS: Onset time and intraoperative conditions were comparable in
      both groups. No patient required general anesthesia to complete surgery. All
      patients from both groups bypassed the postanesthesia care unit. Ambulation took
      place after 27 (18-45) min in Group I and 30 (18-56) min in Group II (P = 0.24).
      Complete regression of spinal anesthesia occurred after 93 (65-120) min in Group
      I and 105 (78-150) min in Group II (P = 0.019); however, no differences were
      observed in time for home discharge 185 (150-300) min in Group I and 188 (125
      300) min in Group II (P = 0.62). Global patient satisfaction was comparable
      between both groups. CONCLUSIONS: Levobupivacaine 3 mg plus 10 microg fentanyl
      may be used as a suitable alternative to 10 mg lidocaine plus 10 microg fentanyl
      for spinal anesthesia of short duration. It achieved a clinically equivalent time
      for resolution of sensory block, similar intraoperative conditions, and
      comparable patient satisfaction..

PMID- 19843784
TI  - The effect of perioperative intravenous lidocaine on postoperative pain and
      immune function.
AB  - BACKGROUND: Surgery-associated tissue injury leads to nociception and
      inflammatory reaction, accompanied by increased production of proinflammatory
      cytokines. These cytokines can induce peripheral and central sensitization,
      leading to pain augmentation. Recently, a frequently used local anesthetic,
      lidocaine, was introduced as a part of a perioperative pain management technique.
      In addition to its analgesic effects, lidocaine has an antiinflammatory property,
      decreasing the upregulation of proinflammatory cytokines. We focused on the
      effects of preincisional and intraoperative IV lidocaine on pain intensity and
      immune reactivity in the postoperative period. METHODS: Sixty-five female
      patients (ASA physical status I-II) scheduled for transabdominal hysterectomy
      were recruited to this randomized, placebo-controlled study. Thirty-two patients
      in the treatment group received IV lidocaine starting 20 min before surgery,
      whereas the control group (33 patients) received a matched saline infusion. Both
      groups received patient-controlled epidural analgesia during the postoperative
      period. Blood samples were collected before, 24, 48, and 72 h after surgery to
      measure ex vivo cytokine production of interleukin (IL)-1 receptor antagonist (IL
      1ra) and IL-6, as well lymphocyte mitogenic response to phytohemagglutinin-M. A
      10-cm visual analog scale was used to assess pain intensity at rest and after
      coughing. RESULTS: Patients in the lidocaine + patient-controlled epidural
      analgesia group experienced less severe postoperative pain in the first 4 and 8 h
      after surgery (visual analog scale 4/3.7 at rest and 5.3/5 during coughing versus
      4.5/4.2 and 6.1/5.3, respectively, in the placebo group). There was significantly
      less ex vivo production of IL-1ra and IL-6, whereas the lymphocyte proliferation
      response to phytohemagglutinin-M was better maintained than in the control group.
      CONCLUSION: The present findings indicate that preoperative and intraoperative IV
      lidocaine improves immediate postoperative pain management and reduces surgery
      induced immune alterations.

PMID- 19843785
TI  - The effects of sevoflurane and propofol on glucose metabolism under aerobic
      conditions in fed rats.
AB  - BACKGROUND: Recent studies reported that intraoperative hyperglycemia is an
      independent risk factor for mortality and morbidity related to surgery. Volatile
      anesthetics, such as sevoflurane, impair glucose use, suggesting their possible
      contributions to intraoperative hyperglycemia. However, the effects of IV
      anesthetics, such as propofol, on glucose metabolism are poorly understood. Thus,
      we compared the effects of sevoflurane and propofol on glucose metabolism under
      aerobic conditions in fed rats. METHODS: We first examined changes in blood
      glucose levels in rats undergoing sigmoid colostomy under sevoflurane,
      sevoflurane/buprenorphine, propofol, and propofol/buprenorphine anesthesia. We
      then examined changes in blood glucose levels after glucose administration using
      awake rats, rats under sevoflurane anesthesia, and rats under propofol
      anesthesia. RESULTS: Blood glucose levels increased markedly after sigmoid
      colostomy under sevoflurane anesthesia; the marked increases could not be
      prevented by the coadministration of buprenorphine. Under propofol anesthesia,
      blood glucose levels did not change after sigmoid colostomy at the highest dose,
      but increased slightly at the lowest and intermediate doses; the slight increases
      were completely prevented by the coadministration of buprenorphine. Whereas
      changes in blood glucose levels after glucose administration in rats under
      sevoflurane anesthesia were significantly greater than those in awake rats, the
      changes in rats under propofol anesthesia were similar to those in awake rats.
      CONCLUSIONS: During surgery, hyperglycemia was observed under sevoflurane and
      sevoflurane/buprenorphine anesthesia, but blood glucose levels were relatively
      stable under propofol and propofol/buprenorphine anesthesia. Whereas sevoflurane
      exaggerates glucose intolerance, propofol has no significant effects on glucose
      tolerance. We speculate that this feature of propofol contributes, at least in
      part, to the stable glucose metabolism during surgery observed in this study. The
      results of this study confirm the marked difference in the effects of sevoflurane
      and propofol on glucose metabolism.

PMID- 19843786
TI  - The role of KATP channels on propofol preconditioning in a cellular model of
      renal ischemia-reperfusion.
AB  - BACKGROUND: Propofol (2,6-diisopropylphenol) has been shown to protect several
      organs, including the kidneys, from ischemia-reperfusion (I-R)-induced injury.
      Although propofol affects adenosine triphosphate-sensitive potassium (K(ATP))
      channels in nonrenal tissues, it is still not clear by which mechanisms propofol
      protects renal cells from such damage. In this study, we investigated whether
      propofol induces renal preconditioning through renal K(ATP) channels. METHODS: A
      reversible ATP depletion (antimycin A) followed by restoration of substrate
      supply in LLC-PK1 cells was used as an in vitro model of renal I-R. Cell
      viability was assessed by dimethylthiazol-diphenyltetrazol bromide and trypan
      blue dye exclusion test assays. Apoptosis was evaluated by annexin V-fluorescein
      isothiocyanate staining by flow cytometry and immunofluorescence. Propofol
      treatments were initiated at various time intervals: 1 or 24 h before ischemia,
      only during ischemia, or only during reperfusion. To evaluate the mechanisms of
      propofol protection, specific K(ATP) channel inhibitors or activators were used
      in some experiments during propofol pretreatment. RESULTS: Propofol attenuated I
      R injury on LLC-PK1 cells when present either 1 or 24 h before initiated I-R, and
      also during the recovery period, but not when added only during ischemia.
      Propofol pretreatment significantly protected LLC-PK1 from I-R-induced apoptosis.
      The protective effect of propofol was prevented by glibenclamide (a sarcolemmal
      ATP-dependent K(+) channel blocker) and decreased by 5-hydroxidecanoic acid (a
      mitochondrial ATP-dependent K(+) channel blocker), but it was not modified by
      diazoxide (a selective opener of ATP-sensitive K(+) channel). CONCLUSION:
      Propofol protected cells against apoptosis induced by I-R. This protection was
      probably due to a preconditioning effect of propofol and was, at least in part,
      mediated by K(ATP) channels.

PMID- 19843787
TI  - Propofol inhibits aquaporin 4 expression through a protein kinase C-dependent
      pathway in an astrocyte model of cerebral ischemia/reoxygenation.
AB  - BACKGROUND: Aquaporin 4 (AQP4) plays a key role in maintaining water balance in
      the central nervous system, and its dysfunction may lead to brain edema. Previous
      studies have suggested that propofol may be involved in neuroprotection by
      preventing brain edema. In this study, we examined the effects of propofol on
      edema and assessed its neuroprotective actions in an oxygen and glucose
      deprivation (OGD) model of cultured rat astrocytes. We assessed the effects of
      propofol on AQP4 expression and the possible role of the protein kinase C (PKC)
      pathway on this effect. METHODS: Neocortical astrocytes were exposed to OGD in an
      anaerobic chamber. After 6 h of OGD exposure, astrocytes were subsequently
      subjected to 24 h of reoxygenation. Propofol was added during the OGD phase of
      the model. Cell morphology was assessed by light microscopy. Astrocyte viability
      was assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide absorbency (optical density value) and the percentage of lactate
      dehydrogenase released by injured astrocytes. AQP4 expression was evaluated with
      Western blot analysis. To investigate the possible mechanism of propofol's
      effects on AQP4 expression, cultured astrocytes were pretreated for 24 h with the
      PKC activator, 12-O-tetradecanoylphorbol 13-acetate, before the propofol
      treatment/OGD 6 h/reoxygenation 24 h. RESULTS: We found by 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide testing that astrocyte viability began to
      decrease after about 4 h of OGD exposure and decreased to 60% after 6 h of OGD.
      When 6 h of OGD was followed by 24 h of reoxygenation, cell viability was further
      decreased. AQP4 expression was attenuated after 6 h of OGD exposure but was
      reversed and exceeded baseline levels after 24 h of reoxygenation. Propofol dose
      dependently reduced cell death assessed by lactate dehydrogenase test (P < 0.05),
      and 10 muM propofol significantly down-regulated AQP4 expression in astrocytes
      after 6 h of OGD followed by 24 h of reoxygenation (P < 0.01). Prolonged (24 h)
      pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate before
      OGD significantly reversed the effect of propofol on AQP4 expression (P < 0.01).
      CONCLUSION: Propofol, administered during OGD, provided neuroprotective effects
      and down-regulated AQP4 expression in the OGD/reoxygenation model of cultured rat
      astrocytes. Activation of the PKC pathway may block the effects of propofol.

PMID- 19843788
TI  - Isoflurane-induced changes in righting response and breathing are modulated by
      RGS proteins.
AB  - BACKGROUND: Recent evidence suggests that G protein-coupled receptors, especially
      those linked to G(alpha)(i), contribute to the mechanisms of anesthetic action.
      Regulator of G protein signaling (RGS) proteins bind to activated G(alpha)(i) and
      inhibit signal transduction. Genomic knock-in mice with an RGS-insensitive
      G(alpha)(i2) G184S (G(alpha)(i2) GS) allele exhibit enhanced G(alpha)(i2)
      signaling and provide a novel approach for investigating the role of G(alpha)(i2)
      signaling and RGS proteins in general anesthesia. METHODS: We anesthetized
      homozygous G(alpha)(i2) GS/GS and wild-type (WT) mice with isoflurane and
      quantified time (in seconds) to loss and resumption of righting response. During
      recovery from isoflurane anesthesia, breathing was quantified in a
      plethysmography chamber for both lines of mice. RESULTS: G(alpha)(i2) GS/GS mice
      required significantly less time for loss of righting and significantly more time
      for resumption of righting than WT mice. During recovery from isoflurane
      anesthesia, G(alpha)(i2) GS/GS mice exhibited significantly greater respiratory
      depression. Poincare analyses show that GS/GS mice have diminished respiratory
      variability compared with WT mice. CONCLUSION: Modulation of G(alpha)(i2)
      signaling by RGS proteins alters loss and resumption of wakefulness and state
      dependent changes in breathing.

PMID- 19843789
TI  - Volatile anesthetics attenuate oxidative stress-reduced activity of glutamate
      transporter type 3.
AB  - BACKGROUND: Volatile anesthetics enhance the activity of glutamate transporter
      Type 3 (also called excitatory amino acid transporter Type 3, EAAT3), the major
      neuronal EAAT. In addition to glutamate, EAAT3 can also uptake L-cysteine, the
      rate-limiting substrate for the synthesis of glutathione. Our previous study
      showed that oxidative stress inhibited glutamate-induced EAAT3 activity. We
      determined whether oxidative stress would reduce L-cysteine-induced EAAT3
      activity and whether this reduction would be attenuated by volatile anesthetics.
      METHODS: Rat EAAT3 was expressed in Xenopus oocytes. L-glutamate- and L-cysteine
      induced membrane currents were recorded using the 2-electrode voltage clamp
      technique. The peak current was quantified to reflect the amount of transported
      substrates because transport of substrates via EAATs is electrogenic. RESULTS:
      Exposure of oocytes to 5 mM tert-butyl hydroperoxide, an organic oxidant, for 10
      min reduced the V(max), but did not affect the K(m), of EAAT3 for L-cysteine. The
      volatile anesthetics isoflurane, sevoflurane, and desflurane at concentrations
      from 1% to 3% attenuated the tert-butyl hydroperoxide-reduced EAAT3 activity for
      L-glutamate and L-cysteine. CONCLUSIONS: Our results suggest that volatile
      anesthetics preserve EAAT3 function to transport L-glutamate and L-cysteine under
      oxidative stress, which may be a mechanism for the neuroprotective effects of
      volatile anesthetics.

PMID- 19843790
TI  - Intraoperative ventilatory strategies for prevention of pulmonary atelectasis in
      obese patients undergoing laparoscopic bariatric surgery.
AB  - BACKGROUND: Atelectasis occurs regularly after induction of general anesthesia,
      persists postoperatively, and may contribute to significant postoperative
      morbidity and additional health care costs. Laparoscopic surgery has been
      reported to be associated with an increased incidence of postoperative
      atelectasis. It has been shown that during general anesthesia, obese patients
      have a greater risk of atelectasis than nonobese patients. Preventing atelectasis
      is important for all patients but is especially important when caring for obese
      patients. METHODS: We randomly allocated 66 adult obese patients with a body mass
      index between 30 and 50 kg/m(2) scheduled to undergo laparoscopic bariatric
      surgery into 3 groups. According to the recruitment maneuver used, the zero end
      expiratory pressure (ZEEP) group (n = 22) received the vital capacity maneuver
      (VCM) maintained for 7-8 s applied immediately after intubation plus ZEEP; the
      positive end-expiratory pressure (PEEP) 5 group (n = 22) received the VCM
      maintained for 7-8 s applied immediately after intubation plus 5 cm H(2)O of
      PEEP; and the PEEP 10 group (n = 22) received the VCM maintained for 7-8 s
      applied immediately after intubation plus 10 cm H(2)O of PEEP. All other
      variables (e.g., anesthetic and surgical techniques) were the same for all
      patients. Heart rate, noninvasive mean arterial blood pressure, arterial oxygen
      saturation, and alveolar-arterial Pao(2) gradient (A-a Pao(2)) were measured
      intraoperatively and postoperatively in the postanesthesia care unit (PACU).
      Length of stay in the PACU and the use of a nonrebreathing O(2) mask (100%
      Fio(2)) or reintubation were also recorded. A computed tomographic scan of the
      chest was performed preoperatively and postoperatively after discharge from the
      PACU to evaluate lung atelectasis. RESULTS: Patients in the PEEP 10 group had
      better oxygenation both intraoperatively and postoperatively in the PACU, lower
      atelectasis score on chest computed tomographic scan, and less postoperative
      pulmonary complications than the ZEEP and PEEP 5 groups. There was no evidence of
      barotrauma in any patient in the 3 study groups. CONCLUSIONS: Intraoperative
      alveolar recruitment with a VCM followed by PEEP 10 cm H(2)O is effective at
      preventing lung atelectasis and is associated with better oxygenation, shorter
      PACU stay, and fewer pulmonary complications in the postoperative period in obese
      patients undergoing laparoscopic bariatric surgery.

PMID- 19843791
TI  - An in vitro analysis of central venous drug delivery by continuous infusion: the
      effect of manifold design and port selection.
AB  - BACKGROUND: Central venous catheters are used extensively in anesthesia and
      critical care. Multiport manifolds allow for simultaneous administration of
      multiple medication infusions into a common central venous catheter lumen. The
      structures of such manifolds vary considerably. In this study, we quantitatively
      compared, in a laboratory model of continuous drug infusion, the drug delivery
      dynamics of a traditional stopcock manifold and a microinfusion manifold
      constructed to minimize dead volume. METHODS: A syringe pump infused a saline
      carrier solution at a low flow rate frequently used in an intensive care unit (10
      mL/h) through a multiport manifold connected to the 16-gauge lumen of a standard
      16-cm triple-lumen catheter. The model drug methylene blue (3 mL/h) joined the
      carrier flow at the first, second, or fourth stopcock of a traditional manifold
      or 1 of 2 positions in a microinfusion manifold, a new device designed to
      minimize dead volume. Effluent samples were collected every minute for
      quantitative spectrophotometric analysis of delivery onset and offset. RESULTS:
      Onset and offset times differed significantly among individual ports of the
      traditional 4-stopcock manifold. There was also a significant difference between
      the 2 ports of the microinfusion manifold, but this was less pronounced. Both
      ports of the microinfusion manifold yielded delivery dynamics that were similar
      to the most downstream port of the 4-stopcock manifold. There was good
      correlation between dynamic data and dead volume for each of the manifolds.
      CONCLUSIONS: Using a traditional stopcock manifold, port selection significantly
      affects drug delivery dynamics for continuous infusions. The findings provide
      quantitative support for the concept that the most critical infusion should join
      the system at the manifold port closest to the patient. Port selection was less
      important for the microinfusion manifold and dynamics were faster compared with
      the second and fourth ports of the stopcock manifold. The smaller dead volumes of
      the microinfusion manifold minimize unwanted delays in drug delivery onset and
      offset allowing more precise control over drug delivery by continuous infusion.

PMID- 19843792
TI  - Misalignment of disposable pulse oximeter probes results in false saturation
      readings that influence anesthetic management.
AB  - We report a small case series in which misaligned disposable pulse oximeter
      sensors gave falsely low saturation readings. In each instance, the sensor
      performed well during preinduction oxygen administration and the early part of
      the case, most notably by producing a plethysmographic trace rated as high
      quality by the oximeter software. The reported pulse oximeter oxygen saturation
      eventually decreased to concerning levels in each instance, but the
      anesthesiologists, relying on the reported high-quality signal, initially sought
      other causes for apparent hypoxia. They undertook maneuvers and diagnostic
      procedures later deemed unnecessary. When the malpositioned sensors were
      discovered and repositioned, the apparent hypoxia was quickly relieved in each
      case. We then undertook a survey of disposable oximeter sensors as patients
      entered the recovery room, and discovered malposition of more than 1 cm in
      approximately 20% of all sensors, without apparent consequence. We conclude that
      the technology is quite robust, but that the diagnosis of apparent hypoxia should
      include a quick check of oximeter position early on.

PMID- 19843793
TI  - Cricoid pressure results in compression of the postcricoid hypopharynx: the
      esophageal position is irrelevant.
AB  - BACKGROUND: Sellick described cricoid pressure (CP) as pinching the esophagus
      between the cricoid ring and the cervical spine. A recent report noted that with
      the application of CP, the esophagus moved laterally more than 90% of the time,
      questioning the efficacy of this maneuver. We designed this study to accurately
      define the anatomy of the Sellick maneuver and to investigate its efficacy.
      METHODS: Twenty-four nonsedated adult volunteers underwent neck magnetic
      resonance imaging with and without CP. Measurements were made of the postcricoid
      hypopharynx, airway compression, and lateral displacement of the cricoid ring
      during the application of CP. The relevant anatomy was reviewed. RESULTS: The
      hypopharynx, not the esophagus, is what lies behind the cricoid ring and is
      compressed by CP. The distal hypopharynx, the portion of the alimentary canal at
      the cricoid level, was fixed with respect to the cricoid ring and not mobile.
      With CP, the mean anterioposterior diameter of the hypopharynx was reduced by 35%
      and the lumen likely obliterated, and this compression was maintained even when
      the cricoid ring was lateral to the vertebral body. CONCLUSIONS: The location and
      movement of the esophagus is irrelevant to the efficiency of the Sellick's
      maneuver (CP) in regard to prevention of gastric regurgitation into the pharynx.
      The hypopharynx and cricoid ring move together as an anatomic unit. This
      relationship is essential to the efficacy and reliability of Sellick's maneuver.
      The magnetic resonance images show that compression of the alimentary tract
      occurs with midline and lateral displacement of the cricoid cartilage relative to
      the underlying vertebral body.

PMID- 19843794
TI  - Substance use among Iranian cardiac surgery patients and its effects on short
      term outcome.
AB  - BACKGROUND: We assessed the prevalence of substance use among patients undergoing
      coronary artery bypass graft and valve surgery in northwest Iran. We evaluated
      the postoperative complications and in-hospital mortality of patients with
      substance dependence and abuse. METHODS: In this prospective, observational
      study, we interviewed 600 patients during the preoperative visit in a tertiary
      referral educational hospital in northwest Iran. The definition of substance
      abuse and dependence was according to DSM-IV criteria. Postoperative
      complications and in-hospital mortality of patients with substance (cigarette,
      opium, and alcohol) dependence and abuse were compared with those in control
      patients who did not use these substances. RESULTS: In 600 studied patients, the
      prevalence of cigarette smoking was 42.1% (ex-smokers 26.0% and current smokers
      16.1%), prevalence of opium use was 12.0% (opium abuse 7.0% and opium dependence
      5.0%), and alcohol consumption was 8.1% (alcohol abuse 7.4% and alcohol
      dependence 0.7%). The prevalence of cigarette smoking was 58.9% in men and 7.6%
      in women (P = 0.001). Postoperative cardiac complications in current smokers
      (21.5%) and ex-smokers (20.5%) were not significantly different from the control
      group (28.2%). Also, pulmonary complications were not different in current
      smokers (24.7%) and ex-smokers (17.9%) from the control group (26.8%; P = 0.196).
      However, in men, pulmonary complications in current smokers were more prevalent
      than in the control group (P = 0.044). In opium and alcohol dependents and
      abusers, postoperative complications were not statistically different from the
      control group (all P values >0.05). No increase was observed regarding in
      hospital mortality in patients with substance use. CONCLUSIONS: In cardiac
      surgery patients in northwest Iran, the prevalence of cigarette smoking is
      relatively low (very low in women), as is alcohol use, compared with Western
      countries; however, opium use is twice as prevalent. We found higher pulmonary
      complication rates in men who smoked, but no increase in postoperative
      cardiopulmonary complications and in-hospital mortality rates in patients who
      abused opium and consumed alcohol.

PMID- 19843795
TI  - Isoflurane preconditioning ameliorates endotoxin-induced acute lung injury and
      mortality in rats.
AB  - BACKGROUND: The effects of isoflurane pretreatment on pulmonary proinflammatory
      cytokines and survival in severe endotoxin-induced acute lung injury (ALI) have
      not been studied systemically. We investigated the effect of preadministration of
      isoflurane on ALI induced by lipopolysaccharide (LPS) in rats. METHODS: Male
      Sprague-Dawley rats weighing 250-300 g were randomly assigned to 1 of 4 groups:
      sham rats (injected intraperitoneally [IP] with saline) pretreated with vehicle
      (100% O(2)) (sham-vehicle); sham rats pretreated with isoflurane (sham-ISO); LPS
      rats (injected IP with LPS) pretreated with vehicle (vehicle-LPS); and LPS rats
      pretreated with isoflurane (ISO-LPS). Endotoxemia was induced by IP injection of
      LPS. Isoflurane 1.4% was administered 30 min before LPS injection. The animals
      were then observed for 6 h. We monitored arterial blood pressure, heart rate, and
      blood gas. The extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye
      extravasation, and histologic examination. We also measured pulmonary nitric
      oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6
      levels. In addition, survival statistics and pulmonary inducible NO synthase
      (iNOS) gene expression were also determined. RESULTS: LPS caused systemic
      hypotension and severe ALI, as evidenced by the increases in the extent of ALI,
      impairment of pulmonary functions, and increases in pulmonary NO, TNF-alpha, IL
      1beta, and IL-6. Isoflurane preconditioning mitigated systemic hypotension and
      the development of ALI. Isoflurane preconditioning also attenuated the LPS
      induced increases in pulmonary nitrate/nitrite and proinflammatory cytokine
      release and improved survival of rats with severe sepsis. The expression of iNOS
      was upregulated by LPS and reduced by isoflurane pretreatment. CONCLUSIONS:
      Isoflurane preconditioning can attenuate pulmonary proinflammatory cytokine
      release and decrease the mortality induced by severe sepsis. Early protection
      seems to be mediated partly through inhibition of iNOS-NO pathway activation.

PMID- 19843796
TI  - A hemodynamic profile for consciousness during cardiopulmonary resuscitation.
AB  - We report the quantification of a hemodynamic profile sufficient to support
      consciousness during cardiopulmonary resuscitation. A 62-yr-old man experienced
      cardiac arrest while being evaluated for heart failure after heart
      transplantation. During the emergency, hemodynamic data were obtained from
      bedside monitors and reviewed at regular intervals. His mean arterial blood
      pressure and heart rate were correlated with consciousness during cardiopulmonary
      resuscitation. A mean arterial blood pressure of 50 mm Hg with a heart rate of
      100 bpm supported consciousness during cardiac arrest. This case helps to
      validate the recent emphasis on hard, fast, basic life support.

PMID- 19843797
TI  - A randomized comparison of low doses of hyperbaric bupivacaine in combined spinal
      epidural anesthesia for cesarean delivery.
AB  - BACKGROUND: The aim of our study was to investigate the block characteristics of
      intrathecal hyperbaric bupivacaine 7, 8, or 9 mg administered during combined
      spinal-epidural anesthesia for cesarean delivery and to elucidate the dose that
      produces adequate sensory blockade for surgery while minimizing the incidence of
      hypotension, high neuroblockade, and the need for intraoperative epidural
      supplementation. METHODS: Sixty women presenting for elective cesarean delivery
      were randomly assigned to one of the 3 groups. Group 7 received intrathecal
      hyperbaric bupivacaine 7 mg, Group 8 received 8 mg, and Group 9 received 9 mg.
      Women in all 3 groups received intrathecal morphine 100 microg and IV
      hydroxyethyl starch 15 mL/kg at the time of initiation of combined spinal
      epidural anesthesia. Surgery began when a sensory level of T4 was achieved.
      Patients were monitored for block characteristics and side effects by a blinded
      observer. Our primary outcome was the maximum cephalad sensory block height.
      RESULTS: There was a difference in the maximum extent of cephalad sensory block
      among groups (Group 7: median T2 [interquartile range T2-T3]; Group 8: median T2
      [T1-T2]; Group 9: median T1 [C8-T2]; P = 0.02). However, the time taken to reach
      T4 was similar in all 3 groups. The incidence of hypotension requiring
      vasopressors was different among groups (30% in Group 7, 55% in Group 8, and 70%
      in Group 9; P = 0.04). No patient had inadequate anesthesia. Neonatal outcomes
      were similar in all 3 groups. CONCLUSION: The lowest dose of hyperbaric
      bupivacaine (7 mg) provided equally rapid onset and effective anesthesia for
      cesarean delivery while reducing the incidence of hypotension compared with 8 and
      9 mg. However, because of its shorter duration of anesthesia, it may be feasible
      only when the block can be reinforced using a functional epidural catheter.

PMID- 19843798
TI  - A randomized controlled trial of pentazocine versus ondansetron for the treatment
      of intrathecal morphine-induced pruritus in patients undergoing cesarean
      delivery.
AB  - BACKGROUND: Ondansetron is effective for the treatment of intrathecal morphine
      induced pruritus. There is evidence that kappa-opioid receptor agonists have
      antipruritic activity. Pentazocine is an agonist of kappa-opioid receptors and
      partial agonist at mu-opioid receptors. We therefore performed a randomized,
      double-blind trial to compare the efficacy of pentazocine and ondansetron for the
      treatment of pruritus associated with intrathecal injection of morphine in
      patients undergoing cesarean delivery. METHODS: Two hundred eight parturients who
      developed moderate to severe pruritus after the administration of intrathecal
      morphine were randomly allocated to 2 groups: IV pentazocine 15 mg (n = 104) and
      IV ondansetron 4 mg (n = 104). The successful treatment of pruritus (no or mild
      pruritus) and other adverse effects were determined 15 min after study drug
      administration, and patients were observed for recurrence of pruritus for 4 h.
      RESULTS: The treatment success rate at 15 min was higher in the pentazocine group
      (96.1%) than in the ondansetron group (80.8%) (95% confidence interval of
      difference: 7.0%, 23.8%; P = 0.001). The recurrence rate of moderate to severe
      pruritus within 4 h after treatment in the pentazocine group (12.0%) was lower
      than in the ondansetron group (32.1%) (P = 0.001). There were no significant
      differences between groups in nausea/vomiting, sedation, shivering, pain scores,
      and pain at injection site. No respiratory depression was observed. CONCLUSIONS:
      Pentazocine 15 mg is superior to ondansetron 4 mg for the treatment of
      intrathecal morphine-induced pruritus and has a lower recurrence rate. The side
      effects after treatment are mild.

PMID- 19843799
TI  - Redesign of a university hospital preanesthesia evaluation clinic using a queuing
      theory approach.
AB  - BACKGROUND: Changes in patient length of stay (the duration of 1 clinic visit) as
      a result of the introduction of an electronic patient file system forced an
      anesthesia department to change its outpatient clinic organization. In this
      study, we sought to demonstrate how the involvement of essential employees
      combined with mathematical techniques to support the decision-making process
      resulted in a successful intervention. METHODS: The setting is the preanesthesia
      evaluation clinic (PAC) of a university hospital, where patients consult several
      medical professionals, either by walk-in or appointment. Queuing theory was used
      to model the initial set-up of the clinic, and later to model possible
      alternative designs. With the queuing model, possible improvements in efficiency
      could be investigated. Inputs to the model were patient arrival rates and
      expected service times with clinic employees, collected from the clinic's logging
      system and by observation. The performance measures calculated with the model
      were patient length of stay and employee utilization rate. Supported by the model
      outcomes, a working group consisting of representatives of all clinic employees
      decided whether the initial design should be maintained or an intervention was
      needed. RESULTS: The queuing model predicted that 3 of the proposed alternatives
      would result in better performance. Key points in the intervention were the
      rescheduling of appointments and the reallocation of tasks. The intervention
      resulted in a shortening of the time the anesthesiologist needed to decide upon
      approving the patient for surgery. Patient arrivals increased sharply over 1 yr
      by more than 16%; however, patient length of stay at the clinic remained
      essentially unchanged. If the initial set-up of the clinic would have been
      maintained, the patient length of stay would have increased dramatically.
      CONCLUSIONS: Queuing theory provides robust methods to evaluate alternative
      designs for the organization of PACs. In this article, we show that queuing
      modeling is an adequate approach for redesigning processes in PACs.

PMID- 19843800
TI  - A cost-effective screening method for preoperative hyperglycemia.
AB  - INTRODUCTION: The preoperative encounter may offer a cost-effective opportunity
      for diabetes screening. METHODS: Three hundred forty-seven fasting patients had a
      preoperative glucose measurement determined from blood residue left on the IV
      needle, measured with an Accu-Chek glucometer (Roche Diagnostics, Indianapolis,
      IN). RESULTS: After excluding patients with a diabetes history, 4.0% had a
      glucose measurement between 100 and 125 mg/dL, at a cost of $14.22 per
      identification, and 1.2% had a glucose measurement more than 125 mg/dL, at a cost
      of $32.00 per identification. CONCLUSIONS: This preoperative blood glucose
      screening test was implemented at a cost of approximately one-tenth of current
      methods.

PMID- 19843801
TI  - Mild hypothermia has no long-term impact on postischemic neurogenesis in rats.
AB  - BACKGROUND: Postischemic improvement of functional outcome by therapeutic
      hypothermia may be related to cerebral regeneration by postischemic neurogenesis.
      We investigated whether mild peri-ischemic hypothermia leads to a long-term
      increase in postischemic neurogenesis. METHODS: Seventy male sevoflurane
      anesthetized Sprague Dawley rats were randomly assigned to the following
      treatment groups: normothermic ischemia, intraischemic hypothermia, and
      postischemic hypothermia with corresponding sham-operated controls. Fifteen naive
      rats were investigated as reference for natural neurogenesis. Forebrain ischemia
      was induced by bilateral common carotid artery occlusion and hemorrhagic
      hypotension. In normothermic groups, the pericranial temperature was maintained
      at 37.5 degrees C. Animals in the hypothermic groups were cooled to a pericranial
      temperature of 33 degrees C for 45 min. All animals received 5-bromo-2
      deoxyuridine for 7 days. Histopathological damage and 5-bromo-2-deoxyuridine
      positive neurons of the hippocampus were analyzed after 28 days. RESULTS:
      Hypothermia had no impact on natural neurogenesis. Cerebral ischemia increased
      the number of new neurons regardless of pericranial temperature. Forty-five
      minutes of hypothermia beginning before ischemia diminished hippocampal injury to
      <10% in the CA1 and CA3 regions, whereas 45 min of postischemic hypothermia
      beginning after reperfusion did not reduce neuronal injury compared with
      normothermia. CONCLUSIONS: Neither intraischemic nor postischemic hypothermia
      affected the ischemia-induced increase in endogenous neurogenesis. Intraischemic
      hypothermia reduced hippocampal damage, whereas postischemic hypothermia as
      applied here did not prevent formation of histopathological injury. This
      indicates that, 28 days after cerebral ischemia, postischemic neurogenesis is not
      significantly increased by mild peri-ischemic hypothermia and not affected by the
      severity of histopathological damage.

PMID- 19843802
TI  - When drugs disappear from the patient: elimination of intravenous medication by
      hemodiafiltration.
AB  - Twenty-three hours after heart transplantation, life-threatening acute right
      heart failure was diagnosed in a patient requiring continuous venovenous
      hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and
      muscle relaxants administered through a central venous catheter were ineffective.
      However, a bolus of epinephrine injected through an alternative catheter provoked
      a hypertensive crisis. Thus, interference with the central venous infusion by the
      dialysis catheter was suspected. The catheters were changed, and hemodynamics
      stabilized at lower catecholamine doses. When the effects of IV drugs are
      inadequate in patients receiving CVVHDF, interference with adjacent catheters
      resulting in elimination of the drug by CVVHDF should be suspected.

PMID- 19843803
TI  - A comparison of gabapentin and ketamine in acute and chronic pain after
      hysterectomy.
AB  - BACKGROUND: Gabapentin and ketamine are popular analgesic adjuvants for improving
      perioperative pain management. We designed this double-blind, placebo-controlled
      study to test and compare the preventive effects of perioperative ketamine and
      gabapentin on early and chronic pain after elective hysterectomy. METHODS: Sixty
      patients undergoing abdominal hysterectomy were randomly assigned to 1 of the
      following 3 groups: control group received oral placebo capsules and bolus plus
      infusion of saline; ketamine group received oral placebo capsules and, before
      incision, 0.3 mg/kg IV bolus and 0.05 mgxkg(-1)xh(-1) infusion of ketamine until
      the end of surgery; and gabapentin group received oral gabapentin 1.2 g and bolus
      plus infusion of saline. The anesthetic technique was standardized, and the
      postoperative assessments included verbal rating scales for pain and sedation, IV
      morphine usage, quality of recovery assessment, recovery of bowel function,
      resumption of normal activities, and patient satisfaction with their pain
      management. Patients were questioned at 1, 3, and 6 mo after surgery for chronic
      postoperative pain. RESULTS: Postoperative pain scores were significantly lower
      in the gabapentin group compared with the ketamine and control groups, and
      patient-controlled analgesia morphine use was significantly reduced in both
      treatment groups (versus control group) (P < 0.001). Total patient-controlled
      analgesia morphine use was decreased by 35% and 42% in the ketamine and
      gabapentin groups, respectively, compared with the control group (P < 0.001).
      Patient satisfaction with pain treatment was significantly improved in the
      ketamine and gabapentin groups compared with the control group (P < 0.001). The
      incidence of incisional pain and related pain scores at the 1-, 3-, and 6-mo
      follow-up were significantly lower in the gabapentin group compared with the
      ketamine and control groups (P < 0.001). CONCLUSION: Gabapentin and ketamine are
      similar in improving early pain control and in decreasing opioid consumption;
      however, gabapentin also prevented chronic pain in the first 6 postoperative
      months.

PMID- 19843804
TI  - Increase in quality, but not quantity, of clinical trials in acute pain: 1992
      versus 2007.
AB  - The annual number of published clinical trials in acute postoperative pain in
      adults has changed little in 15 yr and, as a fraction of all clinical trials
      published in the six highest impact journals in anesthesiology, has actually
      decreased from 16% (95% confidence interval: 12-20) to 11% (95% confidence
      interval: 9-15). However, the methodological quality of reports has improved,
      with explicit statements on power analysis, allocation concealment, and
      specification of primary end points exceeding 90% of reports in 2007. There has
      been a shift in hypothesis interests away from neuraxial analgesia and toward
      multimodal analgesia.

PMID- 19843805
TI  - The effect of a thoracic spinal block on fos expression in the lumbar spinal cord
      of the rat induced by a noxious electrical stimulus at the hindpaw.
AB  - BACKGROUND: Fos expression in the lumbar spinal cord, resulting from a noxious
      electrical stimulus at the hindpaw, is hypothesized to originate from three
      sources: direct sensory input of the noxious stimulus, local interactions in the
      spinal cord, and input of modulating signals from supraspinal regions. Our aim in
      this study was to discriminate among these sources by eliminating the supraspinal
      input. METHODS: Therefore, a spinal block was administered in male Wistar rats by
      administering a local anesthetic (bupivacaine) through an intrathecal catheter at
      the mid-thoracic level. This thoracic spinal block completely suppressed the
      noxious stimulation-induced withdrawal reflex that is normally elicited by
      electrical stimulus. Fos immunoreactivity (Fos-IR) was quantified in all laminae
      of the L4 segment of the spinal cord. RESULTS: Noxious stimulation resulted in a
      general and strong increase in Fos-IR in the ipsilateral dorsal horn, mainly in
      Laminae I, II, and V. Thoracic spinal block caused a remarkable increase in the
      amount of Fos-IR in Lamina V, but had no significant effect on the Fos-IR in
      Laminae I and II. CONCLUSIONS: The increase in Fos-IR in Lamina V may have
      resulted from the interruption of a pain-modulating descending mechanism from the
      brain. A known modulating descending mechanism is the serotonergic system,
      controlled by the periaqueductal gray. This system inhibits the neurons in the
      superficial laminae. Another nonserotonergic system originates in the anterior
      pretectal nucleus. The latter facilitates neurons in the superficial laminae,
      while neurons in Lamina V are inhibited. We conclude that both systems are
      probably involved in the observed effects of the peripheral noxious stimulation
      given in the present model.

PMID- 19843806
TI  - The effects of electroacupuncture on TH1/TH2 cytokine mRNA expression and mitogen
      activated protein kinase signaling pathways in the splenic T cells of traumatized
      rats.
AB  - BACKGROUND: Surgical trauma contributes to postoperative immune suppression,
      which is associated with an increased susceptibility to subsequent infections.
      Electroacupuncture (EA) can alleviate pain and exert immunoregulatory effects.
      However, the mechanism underlying the immnuomodulation effects of EA is not fully
      elucidated. Therefore, we investigated the effects of EA on T helper (Th)1/Th2
      cytokine production and mRNA expression and evaluated the signaling regulatory
      mechanism of EA effects. METHODS: Rats were divided into four groups (n = 24
      each): control, trauma, trauma (T) + sham EA, and T + EA. EA was applied to
      Zusanli (ST36) and Lanwei (Extra37) acupoints at 20 min after surgery for 30 min,
      and then performed once a day on postoperative days 1-5. Splenic T cells were
      isolated and the production and mRNA expression of interleukin (IL)-2, interferon
      gamma, IL-4, and IL-10 were assayed. The activation of mitogen-activated protein
      kinase and the DNA binding activity of nuclear factor (NF)-kappaB and activator
      protein (AP)-1 were examined. RESULTS: Paw withdrawal threshold and paw
      withdrawal latency were significantly increased in the T + EA group compared with
      the trauma group from postoperative day 1 (paw withdrawal threshold: 5.8 +/- 0.7
      vs 3.0 +/- 0.7 g; paw withdrawal latency: 7.0 +/- 0.8 vs 4.5 +/- 0.5 s; P <
      0.001) to day 5 (9.0 +/- 0.6 vs 5.5 +/- 0.6 g; 12.0 +/- 1.3 vs 7.0 +/- 0.8 s; P <
      0.001). Th1 cytokine (IL-2 and interferon-gamma) production and mRNA expression
      in splenic T cells of traumatized rats were significantly decreased on
      postoperative day 3 (P < 0.001, trauma group versus control group), whereas Th2
      cytokine (IL-4 and IL-10) production and mRNA expression were increased (P <
      0.001). This was accompanied with a significant depression in the activity of
      extracellular-regulated protein kinase (ERK)1/2, p38, NF-kappaB, and AP-1 (P <
      0.001, trauma group versus control group). EA administration increased Th1
      cytokine protein and mRNA expression, suppressed Th2 cytokine protein and mRNA
      expression (P < 0.05, T + EA group versus trauma group), and increased the
      activity of ERK1/2, p38, NF-kappaB, and AP-1 (P < 0.001, T + EA group versus
      trauma group). CONCLUSIONS: EA regulates a balance between Th1 and Th2 cytokines
      at protein and mRNA levels in splenic T cells, and, at least in part, involves
      the signaling pathways of ERK1/2, p38, NF-kappaB, and AP-1. The findings suggest
      that EA may improve immune suppression after surgical trauma.

PMID- 19843807
TI  - The effects of ultrasound guidance and neurostimulation on the minimum effective
      anesthetic volume of mepivacaine 1.5% required to block the sciatic nerve using
      the subgluteal approach.
AB  - BACKGROUND: We tested the hypothesis that ultrasound (US) guidance may reduce the
      minimum effective anesthetic volume (MEAV(50)) of 1.5% mepivacaine required to
      block the sciatic nerve with a subgluteal approach compared with neurostimulation
      (NS). METHODS: After premedication and single-injection femoral nerve block, 60
      patients undergoing knee arthroscopy were randomly allocated to receive a sciatic
      nerve block with either NS (n = 30) or US (n = 30). In the US group, the sciatic
      nerve was localized between the ischial tuberosity and the greater trochanter. In
      the NS group, the appropriate muscular response (foot plantar flexion or
      inversion) was elicited (1.5 mA, 2 Hz, 0.1 ms) and maintained to <or=0.5 mA. The
      volume of the injected local anesthetic was varied for consecutive patients based
      on an up-and-down method, according to the response of the previous patient. The
      initial volume was 12 mL. An independent observer evaluated the occurrence of
      complete loss of pinprick sensation and motor block: positive or negative
      responses within 20 min after the injection determined a 2-mL decrease or
      increase for the next patient, respectively. RESULTS: The mean MEAV(50) for
      sciatic nerve block was 12 mL (95% confidence interval [CI], 10-23 mL) in Group
      US and 19 mL (95% CI, 15-23 mL) in Group NS (P < 0.001). The effective dose in
      95% of cases was 14 mL (95% CI, 12-17 mL) in Group US and 29 mL (95% CI, 25-40
      mL) in Group NS (P = 0.008). CONCLUSIONS: US provided a 37% reduction in the
      MEAV(50) of 1.5% mepivacaine required to block the sciatic nerve compared with
      NS.

PMID- 19843808
TI  - An ultra-low dose of naloxone added to lidocaine or lidocaine-fentanyl mixture
      prolongs axillary brachial plexus blockade.
AB  - INTRODUCTION: In this prospective, randomized, double-blind study, we evaluated
      the effect of an ultra-low dose of naloxone added to lidocaine and fentanyl
      mixture on the onset and duration of axillary brachial plexus block. METHODS: One
      hundred twelve patients scheduled for elective forearm surgery under axillary
      brachial plexus block were randomly allocated to receive 34 mL lidocaine 1.5%
      with 3 mL of isotonic saline chloride (control group, n = 28), 34 mL lidocaine
      1.5% with 2 mL (100 microg) of fentanyl and 1 mL of isotonic saline chloride
      (fentanyl group, n = 28), 34 mL lidocaine 1.5% with 2 mL saline chloride and 100
      ng (1 mL) naloxone (naloxone group, n = 28), or 34 mL lidocaine 1.5% with 2 mL
      (100 microg) of fentanyl and 100 ng (1 mL) naloxone (naloxone + fentanyl group, n
      = 28). A multiple stimulation technique was used in all patients. After
      performing the block, sensory and motor blockades of radial, median,
      musculocutaneous, and ulnar nerves were recorded at 5, 15, and 30 min. The onset
      time of the sensory and motor blockades was defined as the time between the last
      injection and the total abolition of the pinprick response and complete
      paralysis, respectively. The duration of sensory and motor blocks was considered
      as the time interval between the complete block and the first postoperative pain
      and complete recovery of motor functions. RESULTS: Sensory and motor onset times
      were longer in the naloxone (sensory onset time: 15 +/- 3, and motor onset time:
      21 +/- 4) and naloxone + fentanyl group than control or fentanyl groups (sensory
      onset time: 10 +/- 3 min in control group, 10 +/- 4 min in fentanyl group, and 17
      +/- 3 min in naloxone + fentanyl group, motor onset time: 15 +/- 5 min in control
      group, 14 +/- 7 min in fentanyl group, and 17.3 +/- 3.4 min in naloxone +
      fentanyl group) (P < 0.001). The duration of time to first postoperative pain and
      motor blockade was significantly longer in the naloxone (92 +/- 10 and 115 +/- 10
      min) and naloxone + fentanyl groups (98 +/- 12 and 122 +/- 16 min) than control
      (68 +/- 7 and 89 +/- 11 min) and fentanyl groups (68 +/- 11 and 90 +/- 12 min) (P
      < 0.001). The time to first postoperative pain was significantly longer in the
      naloxone and naloxone + fentanyl groups than in the control or fentanyl groups (P
      < 0.001). CONCLUSIONS: The addition of an ultra-low dose of naloxone to lidocaine
      1.5% solution with or without fentanyl solution in axillary brachial plexus block
      prolongs the time to first postoperative pain and motor blockade but also
      lengthens the onset time.

PMID- 19843809
TI  - Ropivacaine spinal anesthesia is not antagonized by ondansetron pretreatment.
AB  - BACKGROUND: We investigated a possible effect of ondansetron on the duration of
      sensory and motor block produced by ropivacaine. METHODS: Fifty male patients
      undergoing transurethral surgery received either 8 mg oral ondansetron the
      evening before surgery plus IV 8 mg ondansetron 15 min before subarachnoid
      anesthesia or placebo. All patients received 2.2 mL of 0.75% plain ropivacaine
      intrathecally. Sensory and motor block were assessed 30 min after the intrathecal
      injection and every 30 min thereafter until recovery from the motor block.
      RESULTS: Thirty minutes after spinal injection of ropivacaine, we first measured,
      in both groups, the time to maximum block for both sensory and motor modalities.
      The maximum level of the sensory block, defined as decreased sensation, was T8 in
      the control and T6 in the ondansetron group, and absence of sensation was defined
      as T11 and T9 for the control and the ondansetron groups, respectively. Regarding
      block duration, 180 min after spinal injection, sensory block was detected in 11
      of 22 and 16 of 24 patients and motor block in 1 of 22 and 0 of 24 in the control
      and ondansetron groups, respectively. Sensory and motor block did not differ
      between groups at any measured time point. CONCLUSIONS: Ondansetron had no effect
      on the subarachnoid sensory or motor block produced by ropivacaine.

PMID- 19843810
TI  - Central sensory-motor deficit after uneventful single-dose spinal morphine
      administration in a patient with preexisting migraine headaches.
AB  - Hemiplegic migraine is a condition associated with vascular alteration of the
      central nervous system and transient neurologic deficits. Permanent morphine
      induced motor dysfunction has been reported after spinal ischemia. We report a
      persisting central neurological deficit after single-dose spinal administration
      of 400 microg of morphine in a patient with no previous neurological condition.
      Hemiplegic migraine was thought to be present when the patient emerged from
      anesthesia. Weakness in the left quadriceps and saddle anesthesia of the perineum
      and urinary retention of central origin remained present 3 yr later. Over the 3
      postoperative years, the patient was admitted to a neurological unit 5 times
      because of acute headache associated with complete left-sided hemiplegia. These
      symptoms resolved within 24 h of onset. Hemiplegic migraine was thought to be the
      most likely diagnosis of these recurrent attacks. We hypothesize that the
      patient's persistent deficits were caused by a combination of spinal morphine and
      spinal cord vascular dysfunction associated with hemiplegic migraine.

PMID- 19843811
TI  - Ultrasound-guided paravertebral block using an intercostal approach.
AB  - We describe an ultrasound-guided technique of continuous bilateral paravertebral
      block using an intercostal approach in 12 patients undergoing elective abdominal
      surgery. Postoperatively, each of the patient's paravertebral catheters was
      bolused with 10 mL lidocaine (15 mg/mL), and each of the patient's catheters was
      infused with 0.2% ropivacaine at 10 mL/h. Using a pinprick test, the median
      number of dermatomes blocked after the initial bolus was 5 (interquartile range,
      4-6), and 23 of 24 catheters produced a local anesthetic block. The median verbal
      pain score on postoperative day 1 was 5.5 (interquartile range, 3.5-6), and
      median dose of IV hydromorphone consumed during the first 24 h after surgery was
      1.9 mg (interquartile range, 0.7-5.05). All catheters were removed within 72 h
      after surgery.

PMID- 19843812
TI  - Some unanswered questions about temperature management.

PMID- 19843815
TI  - Are normal echocardiographic values obtained by transthoracic echocardiography in
      awake patients suitable for evaluation of cardiac function in anesthetized and
      mechanically ventilated patients?

PMID- 19843816
TI  - Bowel surgery and multimodal analgesia: same game, new team?

PMID- 19843817
TI  - Recurrence of local anesthetic cardiac toxicity or hypokalemia?

PMID- 19843818
TI  - Quality oversight needed for intraoperative autologous blood recovery and
      readministration.

PMID- 19843820
TI  - Overcoming dose-counting mechanisms on metered-dose inhalers for urgent treatment
      in the operating room.

PMID- 19843819
TI  - Blood infection diagnosis by 16S rDNA broad-spectrum polymerase chain reaction:
      the relationship between antibiotic treatment and bacterial DNA load.

PMID- 19843821
TI  - Continuous transversus abdominis plane block for renal transplant recipients.

PMID- 19843825
TI  - Seduction and insight from cross-national comparisons.

PMID- 19843826
TI  - Diagnosing tuberculosis in patients with HIV: do we know enough?

PMID- 19843827
TI  - Obstructive sleep apnea and the menstrual cycle: potential role of fluid
      retention?

PMID- 19843828
TI  - Indices of hypoxic stress in sleep apnea.

PMID- 19843829
TI  - Comment: evaluation of the modified diet in renal disease equation for
      calculation of carboplatin dose.

PMID- 19843830
TI  - Comment: fatal intracranial bleed potentially due to a warfarin  and influenza
      vaccine interaction.

PMID- 19843832
TI  - Documentation quality in community pharmacy: completeness of electronic patient
      records after patients' first visits.
AB  - BACKGROUND: When patients visit a community pharmacy for the first time, the
      creation of an electronic patient record (EPR) with relevant and up-to-date data
      is a prerequisite for adequate medication surveillance and patient counseling.
      OBJECTIVE: To investigate the level of completeness of documentation in the EPR
      after a patient's first visit to a Dutch community pharmacy. METHODS: In each
      participating pharmacy, newly enlisted (<3 mo) patients to whom at least one
      medication had been dispensed were enrolled in this survey. For each patient who
      could be interviewed, pharmacy master students used a structured questionnaire to
      gather relevant, mandatory patient data (ie, basic characteristics, current drugs
      used, diseases, intolerabilities, specific conditions) and nonmandatory patient
      data (eg, diagnostic and monitoring data, personal experiences and habits, drug
      use problems) from the patient's EPR and from a structured telephone interview
      with the patient. Data retrieved from the patient's EPR were compared with data
      provided by the patient during the telephone interview. RESULTS: Of 403 selected
      patients, 154 (38.2%) could be interviewed by telephone. Poor documentation of
      telephone numbers in the EPR was the main reason for nonresponse (134/249).
      Interviewers found that 67.7% of prescription drugs, 0% of over-the-counter
      drugs, 19.6% of diseases, 3.7% of intolerabilities, and none of the specific
      conditions reported by patients had been documented in the EPR. Nonmandatory data
      (personal experiences and habits, drug use problems) reported during the patient
      interview had not been documented in the EPR. CONCLUSIONS: The EPR after a
      patient's first visit to the community pharmacy is often incomplete. For new
      patients, the pharmacist should more proactively and systematically gather
      patient information, and all relevant information should be recorded, preferably
      in coded form, in the pharmacy information system to allow more adequate clinical
      risk management.

PMID- 19843833
TI  - Evaluation of pharmacist use and perception of Wikipedia as a drug information
      resource.

PMID- 19843834
TI  - Lacosamide: an adjunctive agent for partial-onset seizures and potential therapy
      for neuropathic pain.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of
      lacosamide, a new agent for use as adjunctive treatment in partial-onset seizures
      and a potential agent for treatment of neuropathic pain. DATA SOURCES: A MEDLINE
      search (1966-July 2009) was conducted using the key words lacosamide,
      harkoseride, SPM-927, ADD-234037, epilepsy, anticonvulsant, and neuropathic pain.
      Bibliographies of all articles retrieved were also reviewed. STUDY SELECTION AND
      DATA EXTRACTION: All studies including humans and published in English with data
      describing lacosamide for the adjunctive treatment of partial-onset seizures and
      for treatment of neuropathic pain were reviewed. DATA SYNTHESIS: Lacosamide is a
      functionalized amino acid molecule that selectively enhances the slow
      inactivation of voltage-gated sodium channels and interacts with the collapsin
      response mediator protein-2. With its bioavailability of approximately 100%,
      minimal protein binding, and few drug-drug interactions, lacosamide has a
      favorable pharmacokinetic profile. Recent data suggest that lacosamide may have a
      role as adjunctive treatment of partial-onset seizures. Open-label studies showed
      a 14-47% reduction in seizure frequency, while placebo-controlled trials
      demonstrated a 26-40% reduction in seizure frequency. The 50% responder rates
      ranged from 32.7% to 41.2% with varying doses of lacosamide. Although lacosamide
      use is not approved by the Food and Drug Administration for treatment of
      neuropathic pain, studies demonstrated reductions of 2.01-3.60 in pain scale
      scores. The most common adverse effects, occurring in greater than 10% of
      subjects in the clinical trials, include arthralgia, ataxia, blurred vision,
      diplopia, dizziness, fatigue, headache, injection site pain (only in intravenous
      studies), nausea, tremor, upper respiratory tract infection, and vomiting.
      CONCLUSIONS: Lacosamide is an effective agent for adjunctive treatment of
      refractory partial-onset seizures. Its exact role in the treatment of neuropathic
      pain needs to be determined.

PMID- 19843835
TI  - Possible interaction between topical terbinafine and acenocoumarol.

PMID- 19843836
TI  - Effect of drug information request templates on pharmacy student compliance with
      the modified systematic approach to answering drug information questions.
AB  - BACKGROUND: The modified systematic approach to answering drug information
      questions is a technique used in drug information practice and in teaching
      pharmacy students to effectively provide drug information. Drug information
      request templates were developed to prompt students and other trainees to ask
      appropriate background questions and perform an effective search. OBJECTIVE: An
      evaluation was conducted to determine whether use of drug information templates
      by fourth-year pharmacy students during their drug information experiential
      rotation improved compliance with the modified systematic approach. METHODS:
      Fifty documented drug information requests, including 25 prior to template
      implementation (August 2005-August 2006) and 25 after template implementation
      (August 2007-August 2008), were randomly selected for evaluation. Each question
      was evaluated for completeness of background information obtained, categorization
      and identification of the ultimate question, completeness of references searched,
      and formulation of a concise response and an evidence-based recommendation.
      RESULTS: Background information was complete in 16% of pre-template questions and
      92% of post-template questions (p < 0.001). Eighty-four percent of pre-template
      questions and 96% of post-template questions were appropriately categorized (p =
      0.349). The requestor's ultimate question was clearly identified in 68% of
      pretemplate questions and 92% of post-template questions (p = 0.074). All
      necessary references were searched in 36% of pre-template questions and 88% of
      post-template questions (p < 0.001). A concise response was documented in 80% of
      pretemplate questions and 92% of post-template questions (p = 0.417). In
      questions determined to require a specific recommendation among the pre-template
      (n = 20) and post-template groups (n = 14), a clear and evidence-based
      recommendation was described in 40% (p = 0.038) and 79% (p = 0.038),
      respectively. CONCLUSIONS: Use of drug information request templates improves
      students' compliance with the modified systematic approach, most notably in
      obtaining background information and searching necessary references including
      primary literature.

PMID- 19843837
TI  - Medication use across transition points from the emergency department:
      identifying factors associated with medication discrepancies.
AB  - BACKGROUND: As patients move across transition points of care, medication
      discrepancies are likely to occur. In the emergency department (ED), patients are
      vulnerable to medication discrepancies because they are in an environment in
      which rapid decisions need to be made under high levels of stress. OBJECTIVE: To
      identify the patient-, environment-, and medication-related factors involving
      unexplained medication discrepancies across transition points after ED
      presentation. METHODS: Using a retrospective chart review design, a stratified,
      random sampling of data was undertaken over a 12-month period. Information was
      obtained from an electronic administrative database and medical records as
      patients moved from the ED to another transition point of care. Medication
      discrepancies were classified into 2 outcome groups: (1) no discrepancies and
      situations in which discrepancies were adequately explained and (2) discrepancies
      that had no adequate explanation. RESULTS: For the 12-month period, 210 randomly
      selected patients were included; 73 (34.8%) had at least one unexplained
      medication discrepancy. Binary logistic regression modeling showed 4 factors that
      were statistically significant in determining the incidence of at least one
      unexplained medication discrepancy. Benefit card holders (individuals who receive
      benefits from government insurance programs comparable to the US-based Medicare
      and Medicaid initiatives, which include the elderly, the disabled, low income
      earners, and unemployed persons) had 3.73 greater odds of experiencing an
      unexplained medication discrepancy (95% CI 1.72 to 8.07; p = 0.001). Patients
      prescribed 5 or more drugs at discharge from the ED had 12.22 greater odds of
      having at least one unexplained medication discrepancy (95% CI 5.52 to 27.08; p <
      0.001). Patients who were first seen by a physician within 1 hour of a change in
      working shift had 3.70 greater odds of having an unexplained medication
      discrepancy (95% CI 1.67 to 8.18; p = 0.001). For each additional minute of wait
      time for a physician, the odds of having an unexplained medication discrepancy
      increased by a factor of 1.01 (95% CI 1.00 to 1.01; p = 0.042). CONCLUSIONS:
      Patient-, environment-, and drug-related factors contribute to the risk of
      medication discrepancies across transition points from the ED.

PMID- 19843838
TI  - A comprehensive review of the loop diuretics: should furosemide be first line?
AB  - OBJECTIVE: To review the literature regarding the pharmacokinetic profiles,
      comparative safety and efficacy, and comparative costs of loop diuretics to
      evaluate the current clinical usefulness of furosemide. DATA SOURCES: A search of
      MEDLINE (1966-June 2009) was conducted using the terms furosemide, torsemide,
      bumetanide, ethacrynic acid, and loop diuretics. Articles were limited to those
      written in English. STUDY SELECTION AND DATA EXTRACTION: All English-language
      articles identified from the data sources were reviewed. Studies were eligible if
      they encompassed pharmacokinetics, comparative safety and efficacy, or
      comparative costs of the loop diuretics. DATA SYNTHESIS: In patients with heart
      failure (HF), torsemide demonstrated decreased mortality compared with furosemide
      in 1 study (2.2% vs 4.5% in the furosemide group; p < 0.05), decreased
      hospitalizations in 1 study (23 in the torsemide group vs 61 in the furosemide
      group; p < 0.01), and improved New York Heart Association functional
      classifications in 2 studies. In the first, 45.8% with torsemide versus 37.2%
      with furosemide demonstrated improvement in at least one functional class (p =
      0.00017). In the second, 40.2% with torsemide and 30.7% with furosemide
      demonstrated improvement in at least one functional class (p = 0.014). In 2 of 3
      studies of patients with cirrhosis, torsemide increased natriuresis and total
      volume diuresed compared with furosemide in patients with cirrhosis; however, no
      significant difference between the agents with respect to plasma renin and
      aldosterone concentrations was demonstrated. In patients with pulmonary
      hypertension, central venous pressure, capillary wedge pressure, and stroke
      volume significantly improved from baseline among patients who received
      torsemide, but not in those who received furosemide, although the intergroup
      analysis failed to reach statistical significance. Among patients with chronic
      kidney disease, no significant differences were noted with respect to natriuresis
      and blood pressure control between the 2 agents; however, in patients with acute
      kidney injury, patients who received furosemide had a significant improvement in
      urine output versus the torsemide group. Additionally, 2 trials comparing
      bumetanide with furosemide were identified, although the results were
      conflicting. In patients with nephrotic syndrome, bumetanide significantly
      improved weight loss in the first 4 weeks and in week 20, compared with
      furosemide. In patients with HF, significant improvement in dyspnea at rest and
      on exertion was exhibited in the bumetanide group, but not in the furosemide
      group; no significant difference was noted between the 2 groups when evaluating
      global assessment. CONCLUSIONS: Growing evidence demonstrates more favorable
      pharmacokinetic profiles of torsemide and bumetanide compared with furosemide.
      Furthermore, torsemide may be more efficacious and safer than furosemide in
      patients with HF. A trial comparing all 3 drugs would be required to confirm
      torsemide as the primary loop diuretic in patients with HF, but based upon
      limited current evidence, we recommend torsemide over furosemide. Currently,
      little evidence exists to support either torsemide or bumetanide as first-line
      treatment over furosemide in patients with other edematous disease states.

PMID- 19843839
TI  - Safety of concomitant tamoxifen and warfarin.
AB  - OBJECTIVE: To review the literature regarding the potential interaction between
      tamoxifen and warfarin. DATA SOURCES: A search of MEDLINE from 1948 to August 20,
      2009, was performed using the search terms tamoxifen, warfarin, drug
      interactions, and cytochrome P450 2C9. EMBASE was searched (1980-week 33, 2009),
      using the search terms tamoxifen and warfarin, for articles limited to use in
      humans and published in English, then further narrowed to drug interactions.
      Bibliographic review was conducted but did not reveal any additional references.
      STUDY SELECTION AND DATA EXTRACTION: All sources evaluated were published in
      English and included original case reports, letters, and medical record or
      database reviews that described an interaction between warfarin and tamoxifen.
      DATA SYNTHESIS: Since tamoxifen therapy and cancer increase the risk of venous
      thromboembolism, warfarin may be prescribed to these patients. However, product
      information, primary literature, and tertiary literature describe concomitant use
      of tamoxifen and warfarin as a contraindication since this may increase the level
      of anticoagulation and the risk of bleeding complications. Although the exact
      mechanism of the interaction is unknown, one theory is that tamoxifen inhibits
      CYP2C9, which metabolizes the S-isomer of warfarin. Five publications were
      identified including 2 letters, 2 individual case reports, and 2 retrospective
      reviews (1 of the case reports was included in a medical record review).
      Collectively, these articles described a total of 31 patients taking warfarin and
      tamoxifen concomitantly, with 8 patients experiencing bleeding complications.
      CONCLUSIONS: Although concomitant use of warfarin and tamoxifen is deemed a
      contraindication, evidence regarding this potential interaction is limited.
      Therefore, safety of concomitant use of tamoxifen and warfarin may be similar to
      that of other drugs that interact with warfarin, requiring consistent and careful
      monitoring. However, more evidence is needed to warrant the routine use of this
      combination.

PMID- 19843841
TI  - Does advice from pharmacy staff vary according to the nonprescription medicine
      requested?
AB  - BACKGROUND: Community pharmacy has long been advocated as an appropriate gateway
      of supply for nonprescription medicines and health-related advice. Consumers
      sometimes self-treat the symptoms of minor illness, yet there is conflicting
      evidence over their ability to do so properly. Emerging trends also suggest a
      variable approach to nonprescription medicine supply by pharmacy staff.
      Understanding of this is limited and more structured exploration is needed.
      OBJECTIVE: To explore variation in pharmacy staff response to requests for
      nonprescription medicines from different legislative schedules through analysis
      of data collected using pseudo-patient methods. METHODS: Consumers posed as
      pharmacy patrons (ie, pseudo-patients, simulated patients) and requested 1 of 3
      specific nonprescription medicines by name. Two of these, ibuprofen and a branded
      cold and flu medication, could be sold by any pharmacy staff member (these were
      considered Pharmacy Medicine). The third, a combination analgesic containing
      paracetamol (acetaminophen), codeine, and doxylamine, required pharmacist
      involvement in the sale (considered Pharmacist Only Medicine). Pseudo-patient
      visits measured the service provided in each pharmacy by observing whether staff
      performed particular behaviors such as providing advice regarding the drugs.
      RESULTS: Staff response was generally superior when pseudo-patients requested the
      combination analgesic that required pharmacist intervention. Medicine advice was
      provided verbally to 84.9% of pseudo-patients requesting this analgesic compared
      with 51.1% of those requesting the cold and flu medication. Similar trends were
      observed for other behaviors. CONCLUSIONS: Emerging patterns imply that pharmacy
      staff response may vary according to the medicine requested. It may be that
      pharmacists and their staff prioritize drugs or behaviors that they consider
      critically relevant as part of a risk management approach. This has possible
      implications for future scheduling policy. Further research using a range of
      scenarios would more fully explore the breadth of such behavior. This would aid
      identification of medicines that trigger professional intervention and inform
      development of targeted training programs.

PMID- 19843842
TI  - DIE NEUTRALIS and LATE BLOOMER 1 contribute to regulation of the pea circadian
      clock.
AB  - The DIE NEUTRALIS (DNE) locus in garden pea (Pisum sativum) was previously shown
      to inhibit flowering under noninductive short-day conditions and to affect a
      graft-transmissible flowering signal. In this study, we establish that DNE has a
      role in diurnal and/or circadian regulation of several clock genes, including the
      pea GIGANTEA (GI) ortholog LATE BLOOMER 1 (LATE1) and orthologs of the
      Arabidopsis thaliana genes LATE ELONGATED HYPOCOTYL and TIMING OF CHLOROPHYLL A/B
      BINDING PROTEIN EXPRESSION 1. We also confirm that LATE1 participates in the
      clock and provide evidence that DNE is the ortholog of Arabidopsis EARLY
      FLOWERING4 (ELF4). Circadian rhythms of clock gene expression in wild-type plants
      under constant light were weaker in pea than in Arabidopsis, and a number of
      differences were also seen in the effects of both DNE/ELF4 and LATE1/GI on clock
      gene expression. Grafting studies suggest that DNE controls flowering at least in
      part through a LATE1-dependent mobile stimulus, and dne mutants show elevated
      expression of a FLOWERING LOCUS T homolog under short-day conditions. However,
      the early flowering of the dne mutant is not associated with altered expression
      of a previously described CONSTANS-like gene. Collectively, our results
      characterize the clock system and reveal its importance for photoperiod
      responsiveness in a model legume.

PMID- 19843843
TI  - Distinct microRNA alterations characterize high- and low-grade bladder cancer.
AB  - Urothelial carcinoma of the bladder (UCC) is a common disease that arises by at
      least two different molecular pathways. The biology of UCC is incompletely
      understood, making the management of this disease difficult. Recent evidence
      implicates a regulatory role for microRNA in cancer. We hypothesized that altered
      microRNA expression contributes to UCC carcinogenesis. To test this hypothesis,
      we examined the expression of 322 microRNAs and their processing machinery in 78
      normal and malignant urothelial samples using real-time rtPCR. Genes targeted by
      differentially expressed microRNA were investigated using real-time
      quantification and microRNA knockdown. We also examined the role of aberrant DNA
      hypermethylation in microRNA downregulation. We found that altered microRNA
      expression is common in UCC and occurs early in tumorogenesis. In normal
      urothelium from patients with UCC, 11% of microRNAs had altered expression when
      compared with disease-free controls. This was associated with upregulation of
      Dicer, Drosha, and Exportin 5. In UCC, microRNA alterations occur in a tumor
      phenotype-specific manner and can predict disease progression. High-grade UCC
      were characterized by microRNA upregulation, including microRNA-21 that
      suppresses p53 function. In low-grade UCC, there was downregulation of many
      microRNA molecules. In particular, loss of microRNAs-99a/100 leads to
      upregulation of FGFR3 before its mutation. Promoter hypermethylation is partly
      responsible for microRNA downregulation. In conclusion, distinct microRNA
      alterations characterize UCC and target genes in a pathway-specific manner. These
      data reveal new insights into the disease biology and have implications regarding
      tumor diagnosis, prognosis and therapy.

PMID- 19843844
TI  - p53 Pre- and post-binding event theories revisited: stresses reveal specific and
      dynamic p53-binding patterns on the p21 gene promoter.
AB  - p53 is a master transcription factor that prevents neoplasia and genomic
      instability. It is an important target for anticancer drug design. Understanding
      the molecular mechanisms behind its transcriptional activities in normal cells is
      a prerequisite to further understand the deregulation effected by mutant p53 in
      cancerous cells. Currently, how p53 coordinates transcription programs in
      response to stress remains unclear. One theory proposes that stresses induce pre
      binding events that direct p53 to bind to specific response elements, whereas a
      second posits that, in response to stress, p53 binds most response elements and
      post-binding events then regulate transcription initiation. It is critical to
      establish the relevance of both theories and investigate whether stresses induce
      specific p53-binding patterns correlated with effector gene induction. Using
      unique in cellulo genomic footprinting experiments, we studied p53 binding to the
      five response elements of p21 in response to stresses and monitored p21 mRNA
      variant transcription. We show clear footprints of p53 bound to response elements
      in living cells and reveal that the binding of p53 to response elements is
      transient, subject to dynamic changes during stress responses, and influenced by
      response element pentamer orientations. We show further that stresses lead to
      specific p53-binding patterns correlated with particular p21 mRNA variant
      transcription profiles and that p53 binding is necessary but not sufficient to
      induce p21 transcription. Our results indicate that pre- and post-binding events
      act together to regulate adapted stress responses; this paves the way to the
      unification of pre- and post-binding event theories.

PMID- 19843845
TI  - Presence of the carcinogen N'-nitrosonornicotine in the urine of some users of
      oral nicotine replacement therapy products.
AB  - N'-nitrosonornicotine (NNN) is a strong carcinogen present in unburned tobacco
      and cigarette smoke. We here analyze data obtained in two studies, in which a
      biomarker of exposure to NNN--the sum of NNN and its pyridine-N-glucuronide,
      called total NNN--was quantified in the urine of people who had stopped smoking
      and used various nicotine replacement therapy (NRT) products. In 13 of 34
      nicotine gum or lozenge users from both studies, total NNN at one or more time
      points after biochemically confirmed smoking cessation was comparable with, or
      considerably higher than, the baseline levels. For most of the subjects who used
      the nicotine patch as a smoking cessation aid, urinary total NNN at all post-quit
      time points was <37% of their mean baseline levels. These results indicate that
      endogenous formation of significant amounts of NNN may occur sporadically in some
      users of oral NRT. Given the carcinogenicity of NNN and the frequent use of
      nicotine gum as a smoking cessation aid, further studies are needed so that
      preventive measures can be developed.

PMID- 19843846
TI  - Whole-body sleeping beauty mutagenesis can cause penetrant leukemia/lymphoma and
      rare high-grade glioma without associated embryonic lethality.
AB  - The Sleeping Beauty (SB) transposon system has been used as a somatic mutagen to
      identify candidate cancer genes. In previous studies, efficient leukemia/lymphoma
      formation on an otherwise wild-type genetic background occurred in mice
      undergoing whole-body mobilization of transposons, but was accompanied by high
      levels of embryonic lethality. To explore the utility of SB for large-scale
      cancer gene discovery projects, we have generated mice that carry combinations of
      different transposon and transposase transgenes. We have identified a
      transposon/transposase combination that promotes highly penetrant
      leukemia/lymphoma formation on an otherwise wild-type genetic background, yet
      does not cause embryonic lethality. Infiltrating gliomas also occurred at lower
      penetrance in these mice. SB-induced or accelerated tumors do not harbor large
      numbers of chromosomal amplifications or deletions, indicating that transposon
      mobilization likely promotes tumor formation by insertional mutagenesis of cancer
      genes, and not by promoting wide-scale genomic instability. Cloning of transposon
      insertions from lymphomas/leukemias identified common insertion sites at known
      and candidate novel cancer genes. These data indicate that a high mutagenesis
      rate can be achieved using SB without high levels of embryonic lethality or
      genomic instability. Furthermore, the SB system could be used to identify new
      genes involved in lymphomagenesis/leukemogenesis.

PMID- 19843847
TI  - ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive
      tumors.
AB  - The E2F and MYC transcription factors are critical regulators of cell
      proliferation and contribute to the development of human cancers. Here, we report
      on the identification of a novel E2F target gene, ATAD2, the predicted protein
      product of which contains both a bromodomain and an ATPase domain. The pRB-E2F
      pathway regulates ATAD2 expression, which is limiting for the entry into the S
      phase of the cell cycle. We show that ATAD2 binds the MYC oncogene and stimulates
      its transcriptional activity. ATAD2 maps to chromosome 8q24, 4.3 Mb distal to
      MYC, in a region that is frequently found amplified in cancer. Consistent with
      this, we show that ATAD2 expression is high in several human tumors and that the
      expression levels correlate with clinical outcome of breast cancer patients. We
      suggest that ATAD2 links the E2F and MYC pathways and contributes to the
      development of aggressive cancer through the enhancement of MYC-dependent
      transcription.

PMID- 19843848
TI  - Nuclear receptor coregulators in cancer biology.
AB  - Coregulators (coactivators and corepressors) occupy the driving seat for actions
      of all nuclear receptors, and consequently, selective receptor modulator drugs.
      The potency and selectivity for subreactions of transcription reside in the
      coactivators, and thus, they are critically important for tissue-selective gene
      function. Each tissue has a "quantitative finger print" of coactivators based on
      its relative inherited concentrations of these molecules. When the cellular
      concentration of a coactivator is altered, genetic dysfunction usually leads to a
      pathologic outcome. For example, many cancers overexpress "growth coactivators."
      In this way, the cancer cell can hijack these coactivator molecules to drive
      proliferation and metastasis. The present review contains summaries of selective
      coactivators and corepressors that have been demonstrated to play important roles
      in the malignant process and emphasizes their importance for future therapeutic
      interventions.

PMID- 19843849
TI  - Oncogenic KRAS and BRAF differentially regulate hypoxia-inducible factor-1alpha
      and -2alpha in colon cancer.
AB  - KRAS and BRAF mutations are frequently observed in human colon cancers. These
      mutations occur in a mutually exclusive manner, and each is associated with
      distinctive biological features. We showed previously that K-ras can interact
      with hypoxia to activate multiple signaling pathways. Many hypoxic responses are
      mediated by hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha, and we sought
      to define the roles of mutant KRAS and BRAF in the induction of HIF-1alpha and
      HIF-2alpha in colon cancer cells. Ectopic expression of mutant K-ras in Caco2
      cells enhanced the hypoxic induction of only HIF-1alpha, whereas mutant BRAF
      enhanced both HIF-1alpha and HIF-2alpha. Knockout or knockdown of mutant KRAS in
      DLD-1 and HCT116 cells impaired the hypoxic induction of only HIF-1alpha. HIF
      1alpha mRNA levels were comparable in cells with and without a KRAS mutation.
      However, the rate of HIF-1alpha protein synthesis was higher in cells with a KRAS
      mutation, and this was suppressed by the phosphoinositide 3-kinase inhibitor
      LY294002. In contrast, knockdown of mutant BRAF in HT29 cells suppressed both HIF
      1alpha and HIF-2alpha. Although BRAF regulated mRNA levels of both HIF-1alpha and
      HIF-2alpha, knockdown of BRAF or treatment with the MEK inhibitor PD98059
      impaired the translation of only HIF-2alpha. Our data reveal that oncogenic KRAS
      and BRAF mutations differentially regulate the hypoxic induction of HIF-1alpha
      and HIF-2alpha in colon cancer, and this may potentially contribute to the
      phenotypic differences of KRAS and BRAF mutations in colon tumors.

PMID- 19843850
TI  - Identification of compounds selectively killing multidrug-resistant cancer cells.
AB  - There is a great need for the development of novel chemotherapeutic agents that
      overcome the emergence of multidrug resistance (MDR) in cancer. We catalogued the
      National Cancer Institute's DTP drug repository in search of compounds showing
      increased toxicity in MDR cells. By comparing the sensitivity of parental cell
      lines with MDR derivatives, we identified 22 compounds possessing MDR-selective
      activity. Analysis of structural congeners led to the identification of 15
      additional drugs showing increased toxicity in Pgp-expressing cells. Analysis of
      MDR-selective compounds led to the formulation of structure activity
      relationships and pharmacophore models. This data mining coupled with
      experimental data points to a possible mechanism of action linked to metal
      chelation. Taken together, the discovery of the MDR-selective compound set shows
      the robustness of the developing field of MDR-targeting therapy as a new strategy
      for resolving Pgp-mediated MDR.

PMID- 19843851
TI  - Pegylated kunitz domain inhibitor suppresses hepsin-mediated invasive tumor
      growth and metastasis.
AB  - The transmembrane serine protease hepsin is one of the most highly upregulated
      genes in prostate cancer. Here, we investigated its tumor-promoting activity by
      use of a mouse orthotopic prostate cancer model. First, we compared the tumor
      growth of low hepsin-expressing LnCaP-17 cells with hepsin-overexpressing LnCaP
      34 cells. After implantation of cells into the left anterior prostate lobe, LnCaP
      34 tumors not only grew faster based on increased serum prostate-specific antigen
      levels but also metastasized to local lymph nodes and, most remarkably, invaded
      the contralateral side of the prostate at a rate of 100% compared with only 18%
      for LnCaP-17 tumors. The increased tumor growth was not due to nonspecific gene
      expression changes and was not predicted from the unaltered in vitro growth and
      invasion of LnCaP-34 cells. A likely explanation is that the in vivo effects of
      hepsin were mediated by specific hepsin substrates present in the tumor stroma.
      In a second study, mice bearing LnCaP-34 tumors were treated with a PEGylated
      form of Kunitz domain-1, a potent hepsin active site inhibitor derived from
      hepatocyte growth factor activator inhibitor-1 (K(i)(app) 0.30 +/- 0.02 nmol/L).
      Treatment of established tumors with PEGylated Kunitz domain-1 decreased
      contralateral prostate invasion (46% weight reduction) and lymph node metastasis
      (50% inhibition). Moreover, serum prostate-specific antigen level remained
      reduced during the entire treatment period, reaching a maximal reduction of 76%
      after 5 weeks of dosing. The findings show that hepsin promotes invasive prostate
      tumor growth and metastasis and suggest that active site-directed hepsin
      inhibition could be effective in prostate cancer therapy.

PMID- 19843852
TI  - Hijacking the chromatin remodeling machinery: impact of SWI/SNF perturbations in
      cancer.
AB  - There is increasing evidence that alterations in chromatin remodeling play a
      significant role in human disease. The SWI/SNF chromatin remodeling complex
      family mobilizes nucleosomes and functions as a master regulator of gene
      expression and chromatin dynamics whose functional specificity is driven by
      combinatorial assembly of a central ATPase and association with 10 to 12 unique
      subunits. Although the biochemical consequence of SWI/SNF in model systems has
      been extensively reviewed, the present article focuses on the evidence linking
      SWI/SNF perturbations to cancer initiation and tumor progression in human
      disease.

PMID- 19843853
TI  - Concordant gene expression signatures predict clinical outcomes of cancer
      patients undergoing systemic therapy.
AB  - Conventional development of multivariate gene expression models (GEM) predicting
      therapeutic response of cancer patients is based on analysis of patients treated
      with specific regimens, which limits generalization to different or novel drug
      combinations. We overcome this limitation by developing GEMs based on in vitro
      drug sensitivities and microarray analyses of the NCI-60 cancer cell line panel.
      These GEMs were evaluated in blind fashion as predictors of tumor response and/or
      patient survival in seven independent cohorts of patients with breast (n = 275),
      bladder (n = 59), and ovarian (n= 143) cancer treated with multiagent
      chemotherapy, of which 233 patients were from prospectively enrolled clinical
      trials. In all studies, GEMs effectively stratified tumor response and patient
      survival independent of established clinical and pathologic tumor variables. In
      bladder cancer patients treated with neoadjuvant methotrexate, vinblastine,
      Adriamycin (doxorubicin), and cisplatin, the 3-year overall survival for those
      with favorable GEM scores was 81% versus 33% for those with less favorable scores
      (P = 0.002). GEMs for breast cancer patients treated with 5-fluorouracil,
      Adriamycin (doxorubicin), and cyclophosphamide and ovarian cancer patients
      treated with platinum-containing regimens also stratified patient survival [5
      year overall survival 100% versus 74% (P = 0.05) and 3-year overall survival 68%
      versus 43% (P = 0.008), respectively]. Importantly, clinical prediction using our
      in vitro GEM was superior to that of conventionally derived GEMs. We show a
      facile yet effective approach to GEM derivation that identifies patients most
      likely to benefit from selected multiagent therapy. Use of such in vitro-based
      GEMs may provide a robust and generalizable approach to personalized cancer
      therapy.

PMID- 19843854
TI  - A role for BRCA1 in uterine leiomyosarcoma.
AB  - Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy with a low
      survival rate. Currently, there is no effective treatment for ULMS. Infrequent
      occurrences of human ULMS hamper the understanding of the initiation and
      progression of the disease, thereby limiting the ability to develop efficient
      therapies. To elucidate the roles of the p53 and BRCA1 tumor suppressor genes in
      gynecologic malignancies, we generated mice in which p53 and/or BRCA1 can be
      conditionally deleted using anti-Mullerian hormone type II receptor (Amhr2)
      driven Cre recombinase. We showed that conditional deletion of p53 in mice
      results in the development of uterine tumors that resemble human ULMS and that
      concurrent deletion of p53 and BRCA1 significantly accelerates the progression of
      these tumors. This finding led to our hypothesis that BRCA1 may play a role in
      human ULMS development. Consistent with this hypothesis, we showed that the BRCA1
      protein is absent in 29% of human ULMS and that BRCA1 promoter methylation is the
      likely mechanism of BRCA1 downregulation. These data indicate that the loss of
      BRCA1 function may be an important step in the progression of ULMS. Our findings
      provide a rationale for investigating therapies that target BRCA1 deficiency in
      ULMS.

PMID- 19843855
TI  - Eukaryotic initiation factor 4E binding protein family of proteins: sentinels at
      a translational control checkpoint in lung tumor defense.
AB  - The usurping of translational control by sustained activation of translation
      initiation factors is oncogenic. Here, we show that the primary negative
      regulators of these oncogenic initiation factors--the 4E-BP protein family-
      operate as guardians of a translational control checkpoint in lung tumor defense.
      When challenged with the tobacco carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1
      butanone (NNK), 4ebp1(-/-)/4ebp2(-/-) mice showed increased sensitivity to
      tumorigenesis compared with their wild-type counterparts. The 4E-BP-deficient
      state per se creates pro-oncogenic, genome-wide skewing of the molecular
      landscape, with translational activation of genes governing angiogenesis, growth,
      and proliferation, and translational activation of the precise cytochrome p450
      enzyme isoform (CYP2A5) that bioactivates NNK into mutagenic metabolites. Our
      study provides in vivo proof for a translational control checkpoint in lung tumor
      defense.

PMID- 19843856
TI  - Host lymphodepletion enhances the therapeutic activity of an oncolytic vaccinia
      virus expressing 4-1BB ligand.
AB  - Oncolytic viral vectors have shown promise as antitumor therapeutic agents but
      their effectiveness is complicated by induction of antiviral antibody responses
      and rapid host clearance of recombinant vectors. We developed a recombinant
      oncolytic vaccinia virus expressing the 4-1BBL T-cell costimulatory molecule (rV
      4-1BBL) and showed modest tumor regression in the poorly immunogenic B16 murine
      melanoma model. To improve the therapeutic potential of this vector, we tested
      the antitumor activity of local intratumoral injection in the setting of host
      lymphodepletion, which has been shown to augment vaccination and adoptive T-cell
      therapy. In this model, rV-4-1BBL injection in the setting of lymphodepletion
      promoted MHC class I expression, reduced antiviral antibody titers, promoted
      viral persistence, and rescued effector-memory CD8(+) T cells, significantly
      improving the therapeutic effectiveness of the oncolytic vector. These data
      suggest that vaccination with rV-4-1BBL in the setting of host nonmyeloablative
      lymphodepletion represents a logical strategy for improving oncolytic vaccination
      in melanoma, and perhaps other cancers as well.

PMID- 19843857
TI  - Three-dimensional imaging and quantification of both solitary cells and
      metastases in whole mouse liver by magnetic resonance imaging.
AB  - The metastatic cell population, ranging from solitary cells to actively growing
      metastases, is heterogeneous and unlikely to respond uniformly to treatment.
      However, quantification of the entire experimental metastatic cell population in
      whole organs is complicated by requirements of an imaging modality with the large
      field of view and high spatial resolution necessary to detect both single cells
      and metastases in the same organ. Thus, it is difficult to assess differential
      responses of these distinct metastatic populations to therapy. Here, we develop a
      magnetic resonance imaging (MRI) technique capable of quantifying the full
      population of metastatic cells in a secondary organ. B16F1 mouse melanoma cells
      were labeled with micron-sized iron oxide particles (MPIO) and injected into
      mouse liver via the mesenteric vein. Livers were removed immediately or at day 9
      or 11, following doxorubicin or vehicle control treatment, and imaged using a 3T
      clinical magnetic resonance scanner and custom-built gradient coil. Both
      metastases (>200 microm) and MPIO-labeled single cells were detected and
      quantified from MR images as areas of hyperintensity or hypointensity (signal
      voids), respectively. We found that 1mg/kg doxorubicin treatment inhibited
      metastasis growth (n = 11 per group; P = 0.02, t test) but did not decrease the
      solitary metastatic cell population in the same livers (P > 0.05). Thus, the
      technique presented here is capable of quickly quantifying the majority of the
      metastatic cell population, including both growing metastases and solitary cells,
      in whole liver by MRI and can identify differential responses of growing
      metastases and solitary cells to therapy.

PMID- 19843858
TI  - Activation of the PI3K/AKT pathway induces urothelial carcinoma of the renal
      pelvis: identification in human tumors and confirmation in animal models.
AB  - Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear
      tumorigenic mechanism. We conducted gene expression profiling on a set of human
      tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT
      activation expression signature in 76.9% (n = 13) of our samples. Sequence
      analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of
      heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other
      subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored
      PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial
      carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and
      elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11).
      To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated
      mice containing biallelic inactivation of Pten in the urogenital epithelia. These
      mice developed typical renal pelvic urothelial carcinomas, with an incidence of
      57.1% in mice older than 1 year. Laser capture microdissection followed by PCR
      confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells.
      Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels
      in the animal tumors. Renal lymph node metastases were found in 15.8% of the
      animals with urothelial carcinoma. In conclusion, we identified and confirmed an
      important role for the PI3K/AKT pathway in the development of urothelial
      carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor)
      may serve as effective therapeutic agents.

PMID- 19843859
TI  - Deletion of PTEN promotes tumorigenic signaling, resistance to anoikis, and
      altered response to chemotherapeutic agents in human mammary epithelial cells.
AB  - Many cancers, including breast cancer, harbor loss-of-function mutations in the
      catalytic domain of phosphatase and tensin homologue deleted on chromosome 10
      (PTEN) or have reduced PTEN expression through loss of heterozygosity and/or
      epigenetic silencing mechanisms. However, specific phenotypic effects of PTEN
      inactivation in human cancer cells remain poorly defined without a direct causal
      connection between the loss of PTEN function and the development or progression
      of cancer. To evaluate the biological and clinical relevance of reduced or
      deleted PTEN expression, a novel in vitro model system was generated using human
      somatic cell knockout technologies. Targeted homologous recombination allowed for
      a single and double allelic deletion, which resulted in reduced and deleted PTEN
      expression, respectively. We determined that heterozygous loss of PTEN in the
      nontumorigenic human mammary epithelial cell line MCF-10A was sufficient for
      activation of the phosphoinositide 3-kinase/AKT and mitogen-activated protein
      kinase pathways, whereas the homozygous absence of PTEN expression led to a
      further increased activation of both pathways. The deletion of PTEN was able to
      confer growth factor-independent proliferation, which was confirmed by the
      resistance of the PTEN(-/-) MCF-10A cells to small-molecule inhibitors of the
      epidermal growth factor receptor. However, neither heterozygous nor homozygous
      loss of PTEN expression was sufficient to promote anchorage-independent growth,
      but the loss of PTEN did confer apoptotic resistance to cell rounding and matrix
      detachment. Finally, MCF-10A cells with the reduction or loss of PTEN showed
      increased susceptibility to the chemotherapeutic drug doxorubicin but not
      paclitaxel.

PMID- 19843860
TI  - Simultaneous infiltration of polyfunctional effector and suppressor T cells into
      renal cell carcinomas.
AB  - Renal cell carcinoma is frequently infiltrated by cells of the immune system.
      This makes it important to understand interactions between cancer cells and
      immune cells so they can be manipulated to bring clinical benefit. Here, we
      analyze subsets and functions of T lymphocytes infiltrating renal cell tumors
      directly ex vivo following mechanical disaggregation and without any culture
      step. Subpopulations of memory and effector CD4(+) Th1, Th2, and Th17 and CD8(+)
      Tc1 cells were identified based on surface phenotype, activation potential, and
      multicytokine production. Compared with the same patient's peripheral blood, T
      lymphocytes present inside tumors were found to be enriched in functional CD4(+)
      cells of the Th1 lineage and in effector memory CD8(+) cells. Additionally,
      several populations of CD4(+) and CD8(+) regulatory T cells were identified that
      may synergize to locally dampen antitumor T-cell responses.

PMID- 19843861
TI  - Evidence for cancer stem cells in human endometrial carcinoma.
AB  - Emerging evidence indicates that the highly regenerative human endometrium
      harbors rare populations of epithelial progenitor cells. In tumors of other
      regenerative epithelial tissues, rare cancer stem cells (CSC) have been
      identified that may have originated from normal epithelial stem/progenitor cells.
      We hypothesized that CSC are responsible for epithelial neoplasia associated with
      endometrial carcinoma, the most common gynecologic malignancy in women. Stem cell
      characteristics of single cells isolated from endometrial carcinoma tissues from
      women ages 62 +/- 11.8 years (n = 34) were assessed. Twenty-five of 28
      endometrial carcinoma samples contained a small population of clonogenic cells
      [0.24% (0-1.84%)], with no significant difference in cloning efficiency between
      the three grades of endometrial carcinoma or between endometrial carcinoma and
      normal endometrial epithelial samples. Isolated endometrial carcinoma cells
      transplanted under the kidney capsule of immunocompromised mice in serial
      dilution (2 x 10(6)-1 x 10(4) cells) generated tumors in 8 of 9 samples with
      morphologies similar to the parent tumors. These tumors recapitulated
      cytokeratin, vimentin, estrogen receptor-alpha, and progesterone receptor
      expression of the parent tumor, indicating that tumor-initiating cells likely
      differentiated into cells comprising the endometrial carcinoma tissue. Individual
      clones underwent serial clonal subculture 2.5 to 4 times, with a trend of
      increasing number of subclonings with increasing tumor grade, indicating
      increasing self-renewal with greater malignancy. Clonally derived endometrial
      carcinoma cells also expressed the self-renewal genes BMI-1, NANOG, and SOX-2.
      Isolated cells from primary tumors were serially transplanted 3 to 5 times in
      nonobese diabetic/severe combined immunodeficient mice, showing self-renewal in
      vivo. This evidence of cells with clonogenic, self-renewing, differentiating, and
      tumorigenic properties suggests that a CSC population may be responsible for
      production of endometrial carcinoma tumor cells.

PMID- 19843862
TI  - Identification of key regions and genes important in the pathogenesis of sezary
      syndrome by combining genomic and expression microarrays.
AB  - In this study, we used single nucleotide polymorphism and comparative genomic
      hybridization array to study DNA copy number changes and loss of heterozygosity
      for 28 patients affected by Sezary syndrome (SS), a rare form of cutaneous T-cell
      lymphoma (CTCL). Our data identified, further confirming previous studies,
      recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71% and 68% of
      cases, respectively; common gains were detected for 17p11.2-q25.3 (64%) and
      chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in
      >30% of tumors: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. Individual
      chromosomal aberrations did not show a significant correlation with prognosis;
      however, when more than three recurrent chromosomal alterations (gain or loss)
      were considered, a statistical association was observed using Kaplan-Meier
      survival analysis. Integrating mapping and transcriptional data, we were able to
      identify a total of 113 deregulated transcripts in aberrant chromosomal regions
      that included cancer-related genes such as members of the NF-kappaB pathway
      (BAG4, BTRC, NKIRAS2, PSMD3, and TRAF2) that might explain its constitutive
      activation in CTCL. Matching this list of genes with those discriminating
      patients with different survival times, we identify several common candidates
      that might exert critical roles in SS, such as BUB3 and PIP5K1B. Altogether, our
      study confirms and maps more precisely the regions of gain and loss and, combined
      to transcriptional profiles, suggests a novel set of genes of potential interest
      in SS.

PMID- 19843863
TI  - Intratumoral cytokines and tumor cell biology determine spontaneous breast cancer
      specific immune responses and their correlation to prognosis.
AB  - Spontaneous immune responses in cancer patients have been described. Yet their
      clinical relevance and the conditions for their generation remain unclear. We
      characterized conditions that determine immune responses in primary breast cancer
      patients. We used tetramer analysis, ex vivo IFN-gamma ELISPOT, cytotoxicity
      assays, and ELISA in 207 untreated patients and 12 Her-2/neu-specific CD8 T-cell
      lines to evaluate tumor-specific T cells (TC) in the bone marrow or MUC1-specific
      antibodies in the blood. Multiplex analysis was performed to quantify 27
      intratumoral cytokines, chemokines, and growth factors. Results were compared
      with multiple pathologic and clinical parameters of the patients and tumors.
      Forty percent of the patients showed tumor-specific TC responses. These
      correlated with tumors of high differentiation, estrogen receptor expression, and
      low proliferative activity, and with a reduced cancer mortality risk. High tumor
      cell differentiation correlated with increased intratumoral, but not plasma,
      concentrations of IFN-alpha and reduced transforming growth factor (TGF)beta1. In
      an in vitro priming experiment these two cytokines increased or inhibited,
      respectively, the capacity of dendritic cells to induce tumor-reactive TC. Tumor
      specific B-cell responses, mainly of IgM isotype, were detectable in 50% of the
      patients and correlated with advanced tumor stage, increased TGFbeta1, reduced
      IFN-alpha, and absence of TC responses. We show here that different types of
      immune responses are linked to distinct cytokine microenvironments and correlate
      with prognosis-relevant differences in tumor pathobiology. These findings shed
      light on the relation between immune response and cancer prognosis.

PMID- 19843864
TI  - Pivotal roles of snail inhibition and RKIP induction by the proteasome inhibitor
      NPI-0052 in tumor cell chemoimmunosensitization.
AB  - The novel proteasome inhibitor NPI-0052 has been shown to sensitize tumor cells
      to apoptosis by various chemotherapeutic drugs and tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL), although the mechanisms involved are not
      clear. We hypothesized that NPI-0052-mediated sensitization may result from NF
      kappaB inhibition and downstream modulation of the metastasis inducer Snail and
      the metastasis suppressor/immunosurveillance cancer gene product Raf-1 kinase
      inhibitory protein (RKIP). Human prostate cancer cell lines were used as models,
      as they express different levels of these proteins. We show that NPI-0052
      inhibits both NF-kappaB and Snail and induces RKIP expression, thus resulting in
      cell sensitization to CDDP and TRAIL. The direct role of NF-kappaB inhibition in
      sensitization was corroborated with the NF-kappaB inhibitor DHMEQ, which mimicked
      NPI-0052 in sensitization and inhibition of Snail and induction of RKIP. The
      direct role of Snail inhibition by NPI-0052 in sensitization was shown with Snail
      small interfering RNA, which reversed resistance and induced RKIP. Likewise, the
      direct role of RKIP induction in sensitization was revealed by both
      overexpression of RKIP (mimicking NPI-0052) and RKIP small interfering RNA that
      inhibited NPI-0052-mediated sensitization. These findings show that NPI-0052
      modifies the NF-kappaB-Snail-RKIP circuitry in tumor cells and results in
      downstream inhibition of antiapoptotic gene products and
      chemoimmunosensitization. The findings also identified Snail and RKIP as targets
      for reversal of resistance.

PMID- 19843865
TI  - Constitutive activation of the DNA damage signaling pathway in acute myeloid
      leukemia with complex karyotype: potential importance for checkpoint targeting
      therapy.
AB  - Genomic instability in solid tumors participates in the oncogenetic process and
      is associated with the activation of the DNA damage response pathway. Here, we
      report the activation of the constitutive DNA damage and checkpoint pathway
      associated with complex karyotypes in samples from patients with acute myeloid
      leukemia (AML). We show that antagonizing CHK1 kinase with a small inhibitory
      compound or by RNA interference strongly reduces the clonogenic properties of
      high-DNA damage level AML samples, particularly those with complex karyotypes.
      Moreover, we observe a beneficial effect of CHK1 inhibition in high-DNA damage
      level AML samples treated with 1-beta-d-arabinofuranosylcytosine. In contrast,
      CHK1 inhibition has no effect on the clonogenic properties of normal
      hematopoietic progenitors. All together, our results indicate that CHK1
      inhibition may represent an attractive therapeutic opportunity in AML with
      complex karyotype.

PMID- 19843866
TI  - Regulation of protein Citrullination through p53/PADI4 network in DNA damage
      response.
AB  - Upon a wide range of cellular stresses, p53 is activated and inhibits malignant
      transformation through the transcriptional regulation of its target genes related
      to apoptosis, cell cycle arrest, and DNA repair. However, its involvement in
      posttranslational modifications of proteins has not yet been well characterized.
      Here, we report the novel role of p53 in the regulation of protein
      citrullination. p53 transactivated peptidylarginine deiminase type 4 (PADI4)
      through an intronic p53-binding site. The PADI4 gene encodes an enzyme catalyzing
      the citrullination of arginine residues in proteins, and ectopic expression of
      p53 or PADI4 induced protein citrullination. In addition, various proteins were
      citrullinated in response to DNA damage, but knockdown of PADI4 or p53 remarkably
      inhibited their citrullination, indicating the regulation of protein
      citrullination in a p53/PADI4-dependent manner. We found that PADI4 citrullinated
      the histone chaperone protein, nucleophosmin (NPM1), at the arginine 197 residue
      in vivo under physiologic conditions. Citrullination of NPM1 by PADI4 resulted in
      its translocation from the nucleoli to the nucleoplasm, whereas PADI4 did not
      alter the localization of mutant NPM1 (R197K). Furthermore, ectopic expression of
      PADI4 inhibited tumor cell growth, and concordantly, the knockdown of PADI4
      attenuated p53-mediated growth-inhibitory activity, demonstrating the
      significance of PADI4-mediated protein citrullination in the p53 signaling
      pathway

PMID- 19843867
TI  - Interleukin 12 stimulates IFN-gamma-mediated inhibition of tumor-induced
      regulatory T-cell proliferation and enhances tumor clearance.
AB  - To define the factors that modulate regulatory T (Treg) cells in the tumor
      setting, we cocultured various tumor cells with either purified Treg cells, or
      with unfractionated splenocytes. We found that Treg expansion occurred only with
      unfractionated splenocytes, suggesting that accessory cells and/or factors
      produced by them play an essential role in tumor-induced Treg expansion. We
      performed gene expression profiling on tumor-associated Treg cells to identify
      candidate signaling molecules and studied their effects on tumor-induced Treg
      expansion. We inadvertently discovered that interleukin (IL)-12 treatment blocked
      Treg expansion in an IL-12 receptor-dependent fashion. Additional studies showed
      that IL-12 acts by stimulating IFN-gamma mediated inhibition of Treg cell
      proliferation, which may partially account for the antitumor effects of IL-12.
      Furthermore, IL-12 treatment was found to decrease IL-2 production, which may
      lead to IFN-gamma-independent inhibition of Treg cells, as IL-2 is required for
      their survival and expansion. Mechanistic studies revealed that IFN-gamma
      signaling directly causes cell cycle arrest in Treg cells. This study shows that
      an IL-12-IFN-gamma axis can suppress tumor-induced Treg proliferation. This
      mechanism may counteract the ability of Treg cells to promote tumor growth in
      vivo.

PMID- 19843868
TI  - Comment re: Vitamin C antagonizes the cytotoxic effects of chemotherapy.

PMID- 19843869
TI  - p27Kip1 stabilization is essential for the maintenance of cell cycle arrest in
      response to DNA damage.
AB  - One of the current models of cancer proposes that oncogenes activate a DNA damage
      response (DDR), which would limit the growth of the tumor in its earliest stages.
      In this context, and in contrast to studies focused on the acute responses to a
      one-time genotoxic insult, understanding how cells respond to a persistent source
      of DNA damage might become critical for future studies in the field. We here
      report the discovery of a novel damage-responsive pathway, which involves
      p27(Kip1) and retinoblastoma tumor suppressors and is only implemented after a
      persistent exposure to clastogens. In agreement with its late activation, we show
      that this pathway is critical for the maintenance, but not the initiation, of the
      cell cycle arrest triggered by DNA damage. Interestingly, this late response is
      independent of the canonical ataxia telangiectasia mutated-dependent and ataxia
      telangiectasia mutated and Rad3-related-dependent DDR but downstream of p38
      mitogen-activated protein kinase. Our results might help to reconcile the
      oncogene-induced DNA damage model with the clinical evidence that points to non
      DDR members as the most important tumor suppressors in human cancer.

PMID- 19843871
TI  - Fatty acids induce amylin expression and secretion by pancreatic beta-cells.
AB  - Amylin is the major component of pancreatic amyloid, which is implicated in the
      development of type 2 diabetes. It is costored with insulin in the secretory
      granules of pancreatic beta-cells and cosecreted with insulin following
      stimulation with glucose. Here, we investigate the effect of fatty acids (FAs) on
      amylin expression and secretion by beta-cells and explore the underlying
      mechanisms. Palmitate and oleate dose-dependently induced amylin mRNA
      accumulation in murine pancreatic beta-cell line MIN6 and primary pancreatic
      islets. the inductive effect of FAs on amylin expression is independent of
      glucose concentration. FAs upregulated amylin expression at the transcriptional
      level, and FAs must be metabolized to induce amylin expression. FAs also
      significantly induced human amylin promoter activation. Pretreatment of MIN6
      cells with Ca(2+) chelator (EGTA, BAPTA-AM) PKC inhibitor Go-6976 or protein
      synthesis inhibitor cycloheximide significantly inhibited FA-induced amylin mRNA
      expression. Transcription factors cAMP-responsive element-binding protein,
      pancreatic and duodenal homeobox factor-1, and peroxisome proliferator-activated
      receptor were not involved in FA-induced amylin expression. Palmitate and oleate
      both increased amylin and insulin release from MIN6 cells and stimulated amylin
      expression but had no effect on insulin expression. Mice refed with Intralipid
      had significantly higher levels of plasma FFA, amylin, and insulin than those
      refed with saline. These data demonstrate that FAs differently regulate amylin
      and insulin expression and induce both amylin and insulin release. Ca(2+) and PKC
      signaling pathways and de novo-synthesized protein(s) were involved in FA-induced
      amylin expression. Induction of amylin production and release by FA may
      contribute to its biological functions under physiological conditions.

PMID- 19843872
TI  - Effects of extensively oxidized low-density lipoprotein on mitochondrial function
      and reactive oxygen species in porcine aortic endothelial cells.
AB  - Atherosclerotic cardiovascular disease is the leading cause of mortality in the
      Western world. Dysfunction of the mitochondrial respiratory chain and
      overproduction of reactive oxygen species (ROS) are associated with
      atherosclerosis and cardiovascular disease. Oxidation increases the
      atherogenecity of LDL. Oxidized LDL may be apoptotic or nonapoptotic for vascular
      endothelial cells (EC), depending on the intensity of oxidation. A previous study
      demonstrated that nonapoptotic oxidized LDL increased activity of mitochondrial
      complex I in human umbilical vein EC. The present study examined the impact of
      extensively oxidized LDL (eoLDL) on oxygen consumption and the activities of key
      enzymes in the mitochondrial respiratory chain of cultured porcine aortic EC.
      Oxygraphy detected that eoLDL significantly reduced oxygen consumption in various
      mitochondrial complexes. Treatment with eoLDL significantly decreased NADH
      ubiquinone dehydrogenase (complex I), succinate cytochrome c reductase (complex
      II/III), ubiquinone cytochrome c reductase (complex III), and cytochrome c
      oxidase (complex IV) activities and the NAD+-to-NADH ratio in EC compared with
      mildly oxidized LDL, LDL, or vehicle. Butylated hydroxytoluene, a potent
      antioxidant, normalized eoLDL-induced reductions in complex I and III enzyme
      activity in EC. Mitochondria-associated intracellular ROS and release of ROS from
      EC were significantly increased after eoLDL treatment. These findings suggest
      that eoLDL impairs enzyme activity in mitochondrial respiratory chain complexes
      and increases ROS generation from mitochondria of arterial EC. Collectively,
      these effects could contribute to vascular injury and atherogenesis under
      conditions of hypercholesterolemia and oxidative stress.

PMID- 19843873
TI  - Selective activation of PPARgamma in skeletal muscle induces endogenous
      production of adiponectin and protects mice from diet-induced insulin resistance.
AB  - The nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma plays
      a key role in regulating whole body glucose homeostasis and insulin sensitivity.
      Although it is expressed most highly in adipose, it is also present at lower
      levels in many tissues, including skeletal muscle. The role muscle PPARgamma
      plays in metabolic regulation and in mediating the antidiabetic effects of the
      thiazolidinediones is not understood. The goal of this work was to examine the
      molecular and physiological effects of PPARgamma activation in muscle cells. We
      found that pharmacological activation of PPARgamma in primary cultured myocytes,
      and genetic activation of muscle PPARgamma in muscle tissue of transgenic mice,
      induced the production of adiponectin directly from muscle cells. This muscle
      produced adiponectin was functional and capable of stimulating adiponectin
      signaling in myocytes. In addition, elevated skeletal muscle PPARgamma activity
      in transgenic mice provided a significant protection from high-fat diet-induced
      insulin resistance and associated changes in muscle phenotype, including reduced
      myocyte lipid content and an increase in the proportion of oxidative muscle fiber
      types. Our findings demonstrate that PPARgamma activation in skeletal muscle can
      have a significant protective effect on whole body glucose homeostasis and
      insulin resistance and that myocytes can produce and secrete functional
      adiponectin in a PPARgamma-dependent manner. We propose that activation of
      PPARgamma in myocytes induces a local production of adiponectin that acts on
      muscle tissue to improve insulin sensitivity.

PMID- 19843874
TI  - Novel canine models of obese prediabetes and mild type 2 diabetes.
AB  - Human type 2 diabetes mellitus (T2DM) is often characterized by obesity
      associated insulin resistance (IR) and beta-cell function deficiency. Development
      of relevant large animal models to study T2DM is important and timely, because
      most existing models have dramatic reductions in pancreatic function and no
      associated obesity and IR, features that resemble more T1DM than T2DM. Our goal
      was to create a canine model of T2DM in which obesity-associated IR occurs first,
      followed by moderate reduction in beta-cell function, leading to mild diabetes or
      impaired glucose tolerance. Lean dogs (n = 12) received a high-fat diet that
      increased visceral (52%, P < 0.001) and subcutaneous (130%, P < 0.001) fat and
      resulted in a 31% reduction in insulin sensitivity (S(I)) (5.8 +/- 0.7 x 10(-4)
      to 4.1 +/- 0.5 x 10(-4) microU x ml(-1) x min(-1), P < 0.05). Animals then
      received a single low dose of streptozotocin (STZ; range 30-15 mg/kg). The
      decrease in beta-cell function was dose dependent and resulted in three diabetes
      models: 1) frank hyperglycemia (high STZ dose); 2) mild T2DM with normal or
      impaired fasting glucose (FG), 2-h glucose >200 mg/dl during OGTT and 77-93%
      AIR(g) reduction (intermediate dose); and 3) prediabetes with normal FG, normal 2
      h glucose during OGTT and 17-74% AIR(g) reduction (low dose). Twelve weeks after
      STZ, animals without frank diabetes had 58% more body fat, decreased beta-cell
      function (17-93%), and 40% lower S(I). We conclude that high-fat feeding and
      variable-dose STZ in dog result in stable models of obesity, insulin resistance,
      and 1) overt diabetes, 2) mild T2DM, or 3) impaired glucose tolerance. These
      models open new avenues for studying the mechanism of compensatory changes that
      occur in T2DM and for evaluating new therapeutic strategies to prevent
      progression or to treat overt diabetes.

PMID- 19843875
TI  - Diabetic GK/Par rat beta-cells are spontaneously protected against H2O2-triggered
      apoptosis. A cAMP-dependent adaptive response.
AB  - The alteration of the beta-cell population in the Goto-Kakizaki rat (GK/Par
      line), a model of spontaneous type 2 diabetes, has been ascribed to significantly
      decreased beta-cell replication and neogenesis, while beta-cell apoptosis is
      surprisingly not enhanced and remains in the normal range. To gain insight into
      the mechanisms by which those beta-cells are protected from death, we studied ex
      vivo the apoptotic activity and the expression of a large set of
      pro/antiapoptotic and pro/antioxidant genes in GK/Par islet cells. This was done
      in vitro in freshly isolated islets as well as in response to culture conditions
      and calibrated reactive oxygen species (ROS) exposure (i.e., H2O2). We also
      investigated the intracellular mechanisms of the diabetic beta-cell response to
      ROS, the role if any of the intracellular cAMP metabolism, and finally the
      kinetic of ROS response, taking advantage of the GK/Par rat normoglycemia until
      weaning. Our results show that the peculiar GK/Par beta-cell phenotype was
      correlated with an increased expression of a large panel of antioxidant genes as
      well as pro/antiapoptotic genes. We demonstrate that such combination confers
      resistance to cytotoxic H2O2 exposure in vitro, raising the possibility that at
      least some of the activated stress/defense genes have protective effects against
      H2O2-triggered beta-cell death. We also present some evidence that the GK/Par
      beta-cell resistance to H2O2 is at least partly cAMP dependent. Finally, we show
      that such a phenotype is not innate but is spontaneously acquired after diabetes
      onset as the result of an adaptive response to the diabetic environment.

PMID- 19843876
TI  - Functional analysis of FSP27 protein regions for lipid droplet localization,
      caspase-dependent apoptosis, and dimerization with CIDEA.
AB  - The adipocyte-specific protein FSP27, also known as CIDEC, is one of three cell
      death-inducing DFF45-like effector (CIDE) proteins. The first known function for
      CIDEs was promotion of apoptosis upon ectopic expression in mammalian cells.
      Recent studies in endogenous settings demonstrated key roles for CIDEs in energy
      metabolism. FSP27 is a lipid droplet-associated protein whose heterologous
      expression enhances formation of enlarged lipid droplets and is required for
      unilocular lipid droplets typical of white adipocytes in vivo. Here, we delineate
      relationships between apoptotic function and lipid droplet localization of FSP27.
      We demonstrate that ectopic expression of FSP27 induces enlarged lipid droplets
      in multiple human cell lines, which is indicative that its mechanism involves
      ubiquitously present, rather than adipocyte-specific, cellular machinery.
      Furthermore, promotion of lipid droplet formation in HeLa cells via culture in
      exogenous oleic acid offsets FSP27-mediated apoptosis. Using transient
      cotransfections and analysis of lipid droplets in HeLa cells stably expressing
      FSP27, we show that FSP27 does not protect lipid droplets from action of ATGL
      lipase. Domain mapping with eGFP-FSP27 deletion constructs indicates that lipid
      droplet localization of FSP27 requires amino acids 174-192 of its CIDE C domain.
      The apoptotic mechanism of FSP27, which we show involves caspase-9 and
      mitochondrial cytochrome c, also requires this 19-amino acid region. Interaction
      assays determine the FSP27 CIDE C domain complexes with CIDEA, and Western blot
      reveals that FSP27 protein levels are reduced by coexpression of CIDEA. Overall,
      our findings demonstrate the function of the FSP27 CIDE C domain and/or regions
      thereof for apoptosis, lipid droplet localization, and CIDEA interaction.

PMID- 19843877
TI  - Two-way communication between endometrial stromal cells and monocytes.
AB  - Immune system cells and cells of the endometrium have long been proposed to
      interact in both physiological and pathological processes. The current study was
      undertaken to examine communication between cultured monocytes and endometrial
      stromal cells and also to assess responses of endometrial stromal cells for
      treatment with estradiol (E) in the absence and presence of medroxyprogesterone
      acetate (P). A telomerase-immortalized human endometrial stromal cell (T-HESC)
      line and the U937 monocyte cell line were used. Telomerase-immortalized human
      endometrial stromal cells were treated with E +/- P +/- monocyte conditioned
      medium; U937 were treated +/- T-HESC conditioned medium. Gene expression in
      response to treatment was examined by DNA microarray. Bidirectional
      communication, as demonstrated by changes in gene expression, clearly occurred
      between U937 monocytes and T-HESC.

PMID- 19843878
TI  - High-frequency ultrasound assessment of the murine heart from embryo through to
      juvenile.
AB  - AIM: The aim of this study is to assess the murine heart of normal embryos,
      neonates, and juveniles using high-frequency ultrasound. METHODS: Diastolic
      function was measured with E/A ratio (E wave velocity/A wave velocity) and
      isovolumetric relaxation time (IRT), systolic function with isovolumetric
      contraction time (ICT), percentage fractional shortening (FS %), percentage
      ejection fraction (EF %). Global cardiac performance was quantified using
      myocardial performance index (MPI). RESULTS: Isovolumetric relaxation time
      remained stable from E10.5 to 3 weeks. Systolic function (ICT) improved with
      gestation and remained stable from E18.5 onward. Myocardial performance index
      showed improvement in embryonic life (0.82- 0.63) and then stabilized from 1 to 3
      week (0.60-0.58). Percentage ejection fraction remained high during gestation
      (77%-69%) and then decreased from the neonate to juvenile (68%-51%). CONCLUSION:
      The ultrasound biomicroscope allows for noninvasive in-depth assessment of
      cardiac function of embryos and pups. Detailed physiological and functional
      cardiac function readouts can be obtained, which is invaluable for comparison to
      mouse models of disease.

PMID- 19843879
TI  - Choriodecidual inflammation: a harbinger of the preterm labor syndrome.
AB  - Causal, cellular, and inflammatory links between choriodecidual infection with
      group B streptococcus (GBS) and preterm labor were assessed in a nonhuman primate
      model. Rhesus monkeys received varying doses of a clinical isolate of GBS, type
      III or saline, via an indwelling catheter placed between the chorion/decidua and
      myometrium in the lower pole of the uterus. Choriodecidual inoculation of GBS was
      followed by a graded response in amniotic fluid (AF) leukocytes, proinflammatory
      cytokines, prostaglandin E(2) and F(2alpha), and uterine activity (P < .05). The
      magnitude of the inflammatory response in AF was related, in part, to the initial
      inoculum size and whether AF cultures remained negative or became positive for
      GBS. Microbial invasion of AF was associated with advanced inflammation and
      preterm labor. We provide experimental evidence that choriodeciduitis is a
      transitional stage of intrauterine infection, which may be self-limited, remain
      dormant, or progress to intraamniotic infection. These data, coupled with
      clinical observations, suggest that choriodecidual inflammation is an antecedent
      event in the pathogenesis of premature cervical ripening (functional cervical
      insufficiency), premature rupture of the fetal membranes, or preterm labor.

PMID- 19843880
TI  - Palliative oncology: thalidomide.
AB  - After decades of disuse because of its teratogenic effects, thalidomide has had a
      resurgence of use as a promising therapeutic agent for multiple myeloma. Its
      mechanism of action involves activation of the immune system, antiangiogenic
      effects, and inhibition of cytokines. Thalidomide does not interact with the
      cytochrome oxidase system. It is not significantly metabolized, but it does
      undergo nonenzymatic hydrolysis in plasma. The resulting products are inactive.
      Despite the potential adverse effects of peripheral neuropathy, constipation,
      deep vein thrombosis, somnolence, rash, and orthostatic hypotension, thalidomide
      is an effective first-line agent for multiple myeloma in combination with
      dexamethasone or melphalan and prednisone. It has also been studied in the
      palliative care of patients with cytokine-based syndromes such as anorexia
      cachexia syndrome. This review describes its use in oncology, hematology, and
      palliative care.

PMID- 19843881
TI  - How I treat hairy cell leukemia.
AB  - The description of hairy cell leukemia as a specific clinical entity was
      published 50 years ago. The clinical outcome for patients was hampered by
      ineffective chemotherapy, and splenectomy was the major therapeutic approach to
      improve peripheral blood counts. The median survival after diagnosis was 4 years.
      With the introduction of alpha-interferon in 1984, marked improvements in patient
      responses were observed. Shortly thereafter, the introduction of the purine
      nucleoside analogs transformed this disease into a highly treatable form of
      leukemia, and patients with the classic form of this rare leukemia now have a
      near-normal life expectancy. However, other clinical entities mimicking this
      disease do not respond; thus, accurate diagnosis is important. Immunophenotypic
      features in classic hairy cell leukemia show that the leukemic cells express
      CD11c, CD25, CD103, and CD123 and display bright CD20. Despite the high
      percentage of durable complete remissions with modern therapy, the long-term
      disease-free survival curves have not reached a plateau. Many patients who
      achieve a complete remission by morphologic criteria have minimal residual
      disease demonstrable by either flow cytometry or immunohistochemical staining,
      and this population may be at higher risk for earlier relapse. Continued clinical
      research is essential to optimize therapy for this disease.

PMID- 19843882
TI  - Differential requirement for Gata1 DNA binding and transactivation between
      primitive and definitive stages of hematopoiesis in zebrafish.
AB  - The transcription factor Gata1 is required for the development of erythrocytes
      and megakaryocytes. Previous studies with a complementation rescue approach
      showed that the zinc finger domains are required for both primitive and
      definitive hematopoiesis. Here we report a novel zebrafish gata1 mutant with an N
      ethyl-N-nitrosourea-induced point mutation in the C-finger (gata1(T301K)). The
      Gata1 protein with this mutation bound to its DNA target sequence with reduced
      affinity and transactivated inefficiently in a reporter assay. gata1(T301K/T301K)
      fish had a decreased number of erythrocytes during primitive hematopoiesis but
      normal adult hematopoiesis. We crossed the gata1(T301K/T301K) fish with those
      carrying the R339X mutation, also known as vlad tepes (vlt), which abolishes DNA
      binding and transactivation activities. As we reported previously, gata1(vlt/vlt)
      embryos were "bloodless" and died approximately 11 to 15 days after
      fertilization. Interestingly, the gata1(T301K/vlt) fish had nearly a complete
      block of primitive hematopoiesis, but they resumed hematopoiesis between 7 and 14
      days after fertilization and grew to phenotypically normal fish with normal adult
      hematopoiesis. Our findings suggest that the impact of Gata1 on hematopoiesis
      correlates with its DNA-binding ability and that primitive hematopoiesis is more
      sensitive to reduction in Gata1 function than definitive hematopoiesis.

PMID- 19843883
TI  - IL-21 blockade reduces graft-versus-host disease mortality by supporting
      inducible T regulatory cell generation.
AB  - Interleukin-21 (IL-21) enhances T helper 1 (Th1) and Th17 differentiation while
      inhibiting the conversion of inducible regulatory T cells (Tregs) from naive T
      cells. To determine the role of IL-21 in graft-versus-host disease (GVHD), anti
      IL-21 antibody (Ab) was given to recipients of CD25(-)CD4(+) or CD4(+) and CD8(+)
      T-effectors. IL-21 neutralization attenuated GVHD-related weight loss and
      prolonged survival. Likewise, a majority of mice receiving IL-21(-/-) CD25(-) T
      effectors survived long term, whereas those receiving wild-type T cells died. The
      latter recipients had higher grades of GVHD in the ileum and colon. Surprisingly,
      disruption of IL-21 signaling did not affect IL-17 production, although colon
      infiltrating T-effector cells had decreased interferon gamma (IFNgamma) and
      increased IL-4 production. FoxP3(+) Tregs were increased in colons of anti-IL-21
      Ab-treated recipients of FoxP3(-) IL-21(-/-) T cells, indicating Treg conversion.
      Recipients of FoxP3-deficient T-effectors isolated from chimeras were resistant
      to the GVHD protective effects of IL-21 blockade. Whereas graft-versus-leukemia
      (GVL) can occur in the absence of IL-21, loss of both IL-21 and perforin
      expression abrogated GVL. Together, these data indicate that IL-21 suppresses
      inducible Treg conversion and further suggest that IL-21 blockade is an
      attractive strategy to reduce GVHD-induced injury.

PMID- 19843885
TI  - Appearance of peripheral blood plasma cells and memory B cells in a primary and
      secondary immune response in humans.
AB  - In humans, the kinetics of the appearance of memory B cells and plasma cells
      during primary immunization are not well defined. In this study, we assessed the
      primary B-cell response of rabies-antigen naive volunteers during a 3-dose course
      of rabies vaccine compared with the B-cell response to a booster dose of rabies
      vaccine given to previously immunized volunteers. After a single dose of vaccine,
      in the naive group plasma and memory B cells appeared later (peak at day 10) than
      in the primed group (peak at day 7) and were at lower frequency. The most rapid
      responses (day 4) were detected after a third immunization in the naive group.
      This is the first study to document the detailed kinetics of the plasma cell and
      memory B-cell responses to immunization in adult humans and to demonstrate
      differences in the responses that relate to the preexisting immune status of the
      persons.

PMID- 19843884
TI  - Aspergillus fumigatus inhibits angiogenesis through the production of gliotoxin
      and other secondary metabolites.
AB  - In susceptible hosts, angioinvasion by Aspergillus fumigatus triggers thrombosis,
      hypoxia, and proinflammatory cytokine release, all of which are stimuli for
      angiogenesis. We sought to determine whether A fumigatus directly modulates
      angiogenesis. A fumigatus culture filtrates profoundly inhibited the
      differentiation, migration, and capillary tube formation of human umbilical vein
      endothelial cells in vitro. To measure angiogenesis at the site of infection, we
      devised an in vivo Matrigel assay in cyclophosphamide-treated BALB/c mice with
      cutaneous invasive aspergillosis. Angiogenesis was significantly suppressed in
      Matrigel plugs implanted in A fumigatus-infected mice compared with plugs from
      uninfected control mice. The antiangiogenic effect of A fumigatus was completely
      abolished by deletion of the global regulator of secondary metabolism, laeA, and
      to a lesser extent by deletion of gliP, which controls gliotoxin production.
      Moreover, pure gliotoxin potently inhibited angiogenesis in vitro in a dose
      dependent manner. Finally, overexpression of multiple angiogenesis mediator
      encoding genes was observed in the lungs of cortisone-treated mice during early
      invasive aspergillosis, whereas gene expression returned rapidly to baseline
      levels in cyclophosphamide/cortisone-treated mice. Taken together, these results
      indicate that suppression of angiogenesis by A fumigatus both in vitro and in a
      neutropenic mouse model is mediated through secondary metabolite production.

PMID- 19843886
TI  - Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute
      lymphoblastic leukemia patients with BCR-ABL T315I mutation.
AB  - The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine
      kinase inhibitors (TKIs). The objectives of this retrospective observational
      study were to estimate overall and progression-free survival for chronic myeloid
      leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and
      Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL)
      patients with T315I mutation. Medical records of 222 patients from 9 countries
      were reviewed; data were analyzed using log-rank tests and Cox proportional
      hazard models. Median age at T315I mutation detection was 54 years; 57% cases
      were men. Median time between TKI treatment initiation and T315I mutation
      detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and
      Ph(+) ALL patients. After T315I mutation detection, second-generation TKIs were
      used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK
      0457 in 11%, stem cell transplantation in 17%, and interferon-alpha in 6% of
      cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0,
      and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5
      months, respectively, for CP, AP, BP, and Ph(+) ALL patients. These results
      confirm that survival of patients harboring a T315I mutation is dependent on
      disease phase at the time of mutation detection.

PMID- 19843888
TI  - Putting risk prediction in perspective: relative utility curves.
AB  - Risk prediction models based on medical history or results of tests are
      increasingly common in the cancer literature. An important use of these models is
      to make treatment decisions on the basis of estimated risk. The relative utility
      curve is a simple method for evaluating risk prediction in a medical decision
      making framework. Relative utility curves have three attractive features for the
      evaluation of risk prediction models. First, they put risk prediction into
      perspective because relative utility is the fraction of the expected utility of
      perfect prediction obtained by the risk prediction model at the optimal cut
      point. Second, they do not require precise specification of harms and benefits
      because relative utility is plotted against a summary measure of harms and
      benefits (ie, the risk threshold). Third, they are easy to compute from standard
      tables of data found in many articles on risk prediction. An important use of
      relative utility curves is to evaluate the addition of a risk factor to the risk
      prediction model. To illustrate an application of relative utility curves, an
      analysis was performed on previously published data involving the addition of
      breast density to a risk prediction model for invasive breast cancer.

PMID- 19843889
TI  - The cover. The court jester Stanczyk (1480-1560) receives news of the loss of
      Smolensk (1514), during a ball at Queen Bona's court.

PMID- 19843887
TI  - Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and
      rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.
AB  - Preclinical data demonstrate enhanced antitumor effect when lumiliximab, an anti
      CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical
      data from a phase 1 trial with lumiliximab demonstrated an acceptable toxicity
      profile in patients with relapsed or refractory chronic lymphocytic leukemia
      (CLL). We therefore pursued a phase 1/2 dose-escalation study of lumiliximab
      added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated
      CLL patients. Thirty-one patients received either 375 mg/m(2) (n = 3) or 500
      mg/m(2) (n = 28) of lumiliximab in combination with FCR for 6 cycles. The
      toxicity profile was similar to that previously reported for FCR in treatment of
      relapsed CLL. The overall response rate was 65%, with 52% of patients achieving a
      complete response (CR), which compares favorably with the CR rate previously
      reported for the FCR regimen alone in relapsed CLL. The estimated median
      progression-free survival for all responders was 28.7 months. The addition of
      lumiliximab to FCR therapy is feasible, achieves a high CR rate, and does not
      appear to enhance toxicity in previously treated patients with CLL. A randomized
      trial comparing lumiliximab plus FCR with FCR alone is underway to define the
      benefit of this combination in relapsed CLL. This trial was registered at
      clinicaltrials.gov as NCT00103558.

PMID- 19843890
TI  - A piece of my mind. Can we agree to disagree?

PMID- 19843891
TI  - Despite health claims by manufacturers, little oversight for homeopathic
      products.

PMID- 19843892
TI  - IOM offers new guidance in crisis care.

PMID- 19843893
TI  - Ratings game: lists of "top" physicians, hospitals has unclear impact on public.

PMID- 19843894
TI  - Corticosteroid therapy for severe sepsis and septic shock.

PMID- 19843895
TI  - Corticosteroid therapy for severe sepsis and septic shock.

PMID- 19843896
TI  - Lipoprotein(a) measurement and determining risk of myocardial infarction.

PMID- 19843897
TI  - Diabetes in Asian immigrant populations.

PMID- 19843898
TI  - Donor availability and clinical trials for allogeneic stem cell transplantation.

PMID- 19843899
TI  - Omega-3 augmentation of sertraline in treatment of depression in patients with
      coronary heart disease: a randomized controlled trial.
AB  - CONTEXT: Studies of depressed psychiatric patients have shown that antidepressant
      efficacy can be increased by augmentation with omega-3 fatty acids. OBJECTIVE: To
      determine whether omega-3 improves the response to sertraline in patients with
      major depression and coronary heart disease (CHD). DESIGN, SETTING, AND
      PARTICIPANTS: Randomized controlled trial. Between May 2005 and December 2008,
      122 patients in St Louis, Missouri, with major depression and CHD were
      randomized. INTERVENTIONS: After a 2-week run-in period, all patients were given
      50 mg/d of sertraline and randomized in double-blind fashion to receive 2 g/d of
      omega-3 acid ethyl esters (930 mg of eicosapentaenoic acid [EPA] and 750 mg of
      docosahexaenoic acid [DHA]) (n=62) or to corn oil placebo capsules (n=60) for 10
      weeks. MAIN OUTCOME MEASURES: Scores on the Beck Depression Inventory (BDI-II)
      and the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Adherence to the
      medication regimen was 97% or more in both groups for both medications. There
      were no differences in weekly BDI-II scores (treatment x time interaction = 0.02;
      95% confidence interval [CI], -0.33 to 0.36; t(112) = 0.11; P = .91), pre-post
      BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, -4.5
      to 2.0; t(116) = -0.77; P = .44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3;
      95% difference-in-means CI, -2.2 to 2.4; t(115) = 0.12; P = .90). The groups did
      not differ on predefined indicators of depression remission (BDI-II < or = 8:
      placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15;
      t(113) = -0.11; P = .91) or response (> 50% reduction in BDI-II from baseline:
      placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t(112) = 0.15; P =
      .88). CONCLUSIONS: Treatment of patients with CHD and major depression with
      sertraline and omega-3 fatty acids did not result in superior depression outcomes
      at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega
      3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3
      monotherapy can improve depression in patients with CHD remains to be determined.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00116857.

PMID- 19843900
TI  - Use of aldosterone antagonists in heart failure.
AB  - CONTEXT: Aldosterone antagonists are recommended for patients with moderate to
      severe heart failure (HF) and systolic dysfunction. Prior studies suggest
      underuse of aldosterone antagonists in eligible patients as well as overuse in
      settings in which therapy may be harmful. OBJECTIVE: To examine aldosterone
      antagonist prescription based on HF management guideline criteria, investigator
      defined appropriateness criteria, and trends over time in patients hospitalized
      with heart failure. DESIGN, SETTING, AND PATIENTS: Observational analysis of
      43,625 patients admitted with HF and discharged home from 241 hospitals
      participating in the Get With The Guidelines-HF quality improvement registry
      between January 2005 and December 2007. MAIN OUTCOME MEASURES: Prescription and
      predictors of use of aldosterone antagonists, based on guideline criteria.
      RESULTS: Among 12,565 patients eligible for aldosterone antagonist therapy, 4087
      (32.5%) received an aldosterone antagonist at discharge, and treatment increased
      modestly from 28% to 34% over the study period. There was also wide variation in
      aldosterone antagonist use among hospitals (0%-90.6%). Aldosterone antagonist use
      in eligible patients was associated with younger age (adjusted odds ratio [OR],
      0.85; 95% confidence interval [CI], 0.82-0.88), African American race/ethnicity
      (adjusted OR, 1.17; 95% CI, 1.04-1.32), lower systolic blood pressure (adjusted
      OR, 0.94; 95% CI, 0.92-0.95), history of implantable cardioverter-defibrillator
      use (adjusted OR, 1.51; 95% CI, 1.34-1.69), depression (adjusted OR, 1.15; 95%
      CI, 1.01-1.30), alcohol use (adjusted OR, 1.23; 95% CI, 1.02-1.50), and pacemaker
      implantation (adjusted OR, 1.21; 95% CI, 1.06-1.38), and with having no history
      of renal insufficiency (adjusted OR, 0.85; 95% CI, 0.75-0.96). Applying serum
      creatinine and potassium appropriateness criteria, inappropriate and potentially
      inappropriate use of aldosterone antagonist therapy was low and did not change
      over the 3-year study period. CONCLUSIONS: Less than one-third of eligible
      patients hospitalized for HF and participating in a quality improvement registry
      received HF guideline-recommended aldosterone antagonist therapy. Use of
      aldosterone antagonist therapy among patients with documented contraindications
      was low.

PMID- 19843901
TI  - Cardiovascular diseases and risk of hip fracture.
AB  - CONTEXT: Recent studies indicate common etiologies for cardiovascular disease
      (CVD) and osteoporotic fractures. OBJECTIVES: To examine the relation between CVD
      and risk of hip fracture in twins and evaluate the relative importance of
      genetics and lifestyle factors in this association. DESIGN, SETTING, AND
      PARTICIPANTS: A cohort of all 31,936 Swedish twins born from 1914-1944 was
      followed up from the age of 50 years. The National Patient Registry identified
      twins with CVDs and fractures from 1964 through 2005. Time-dependent exposures
      using Cox proportional hazard regression models were evaluated. MAIN OUTCOME
      MEASURE: Time to hip fracture after diagnosis of CVD. RESULTS: The crude absolute
      rate of hip fractures was 12.6 per 1000 person-years after a diagnosis of heart
      failure, 12.6 per 1000 person-years after a stroke, 6.6 per 1000 person-years
      after a diagnosis of peripheral atherosclerosis, and 5.2 per 1000 person-years
      after a diagnosis of ischemic heart disease compared with 1.2 per 1000 person
      years for those without a CVD diagnosis. The multivariable-adjusted hazard ratio
      (HR) of hip fracture after a diagnosis of heart failure was 4.40 (95% confidence
      interval [CI], 3.43-5.63); after a stroke, the HR was 5.09 (95% CI, 4.18-6.20);
      after a diagnosis of peripheral atherosclerosis, the HR was 3.20 (95% CI, 2.28
      4.50); and after an ischemic heart disease event, the HR was 2.32 (95% CI, 1.91
      2.84). Identical twins without heart failure and stroke also had, after their co
      twins had been exposed to these respective diseases, an increased rate of hip
      fracture. These sibling twins pseudoexposed for heart failure had a multivariable
      adjusted HR of 3.74 (95% CI, 1.97-7.10) for hip fracture, whereas pseudoexposure
      for stroke had an HR of 2.29 (95% CI, 1.20-4.35). CONCLUSIONS: A diagnosis of CVD
      was significantly associated with risk of subsequent hip fracture. Increased
      risks in co-twins without an index diagnosis suggest genetic factors in the
      association between CVD and osteoporotic fractures.

PMID- 19843902
TI  - Comparison of physician workforce estimates and supply projections.
AB  - CONTEXT: Estimates of physician supply in the United States have been based on
      data that may overestimate the number of older physicians in the workforce.
      OBJECTIVE: To compare physician workforce estimates and supply projections using
      the American Medical Association Physician Masterfile (Masterfile) data with
      estimates and projections using data from the US Census Bureau Current Population
      Survey (CPS). DESIGN, SETTING, AND PARTICIPANTS: Parallel retrospective cohort
      analyses of employment trends of the number of active physicians by age and sex
      using annual data from the Masterfile and the CPS between 1979 and 2008. Recent
      workforce trends were used to project future physician supply by age. MAIN
      OUTCOME MEASURE: Annual number of physicians working at least 20 hours per week
      in 10-year age categories. RESULTS: In an average year in the sample period, the
      CPS estimated 67,000 (10%) fewer active physicians than did the Masterfile (95%
      confidence interval [CI], 57,000-78,000; P < .001), almost entirely due to fewer
      active physicians aged 55 years or older. The CPS estimated more young physicians
      (ages 25-34 years) than did the Masterfile, with the difference increasing to an
      average of 17,000 (12%) during the final 15 years (95% CI, 13,000-22,000; P <
      .001). The CPS estimates of more young physicians were consistent with historical
      growth observed in the number of first-year residents, and the CPS estimates of
      fewer older physicians were consistent with lower Medicare billing by older
      physicians. Projections based on both the CPS and the Masterfile data indicate
      that the number of active physicians will increase by approximately 20% between
      2005 and 2020. However, projections for 2020 using CPS data estimate nearly
      100,000 (9%) fewer active physicians than projections using the Masterfile data
      (957,000 vs 1,050,000), and estimate that a smaller proportion of active
      physicians will be 65 years or older (9% vs 18%). The increasing proportion of
      female physicians had little effect on physician supply projections because,
      unlike male physicians, female physicians were found to maintain their work
      activity after age 55 years. CONCLUSION: Compared with the Masterfile data,
      estimates using the CPS data found more young physicians entering the workforce
      and fewer older physicians remaining active, resulting in estimates of a smaller
      and younger physician workforce now and in the future.

PMID- 19843903
TI  - Implications of hypertrophic cardiomyopathy transmitted by sperm donation.
AB  - CONTEXT: Sperm donation is an increasingly common practice for achieving
      pregnancy in the absence of a male partner or when fertility is problematic. The
      unintended consequence in which genetic diseases are unwittingly transmitted to
      offspring is an underrecognized public health issue not previously prioritized by
      US Food and Drug Administration guidelines. OBJECTIVE: To report the clinical
      circumstances and implication of hypertrophic cardiomyopathy (HCM) transmitted by
      sperm donation to recipients. SETTING: Voluntary sperm donation through a US Food
      and Drug Administration-approved tissue bank. MAIN OUTCOME MEASURE: Incidence of
      genetically affected offspring and clinical outcomes to date. RESULTS: An
      asymptomatic 23-year-old man who had no personal knowledge of underlying heart
      disease and who underwent standard testing that was negative for infectious
      diseases, repeatedly donated sperm over a 2-year period (1990-1991). The donor
      was later shown to be affected (in 2005) by a novel beta-myosin heavy-chain
      mutation that caused HCM, after an offspring was clinically diagnosed with this
      disease. Of the 24 children known to be offspring of the donor, including 22 who
      were products of fertilization via sperm donation and 2 conceived by the donor's
      wife, a total of 9 genetically affected offspring, 2 to 16 years of age and 6
      males, have been identified with HCM (2005-2009). Three of the 9 gene-positive
      children have currently expressed phenotypic evidence of HCM, including one who
      died at age 2 years due to progressive and unrelenting heart failure with marked
      hypertrophy, and also 2 survivors with extreme left ventricular hypertrophy at
      age 15 years. The latter 2 children and the donor are judged likely to be at
      increased risk for sudden death. CONCLUSIONS: This case series underscores the
      potential risk for transmission of inherited cardiovascular diseases through
      voluntary sperm donation, a problem largely unappreciated by the medical
      community and agencies regulating tissue donation. Recommendations include
      improved screening guidelines for donors to exclude cardiovascular diseases (eg,
      HCM) such as consideration for 12-lead electrocardiograms.

PMID- 19843904
TI  - Rethinking screening for breast cancer and prostate cancer.
AB  - After 20 years of screening for breast and prostate cancer, several observations
      can be made. First, the incidence of these cancers increased after the
      introduction of screening but has never returned to prescreening levels. Second,
      the increase in the relative fraction of early stage cancers has increased.
      Third, the incidence of regional cancers has not decreased at a commensurate
      rate. One possible explanation is that screening may be increasing the burden of
      low-risk cancers without significantly reducing the burden of more aggressively
      growing cancers and therefore not resulting in the anticipated reduction in
      cancer mortality. To reduce morbidity and mortality from prostate cancer and
      breast cancer, new approaches for screening, early detection, and prevention for
      both diseases should be considered.

PMID- 19843905
TI  - Differences in colon adenomas and carcinomas among women and men: potential
      clinical implications.

PMID- 19843906
TI  - Variation in event rates in trials of patients with type 2 diabetes.

PMID- 19843907
TI  - How many physicians? How much does it matter?

PMID- 19843908
TI  - Genetic screening of sperm and oocyte donors: ethical and policy implications.

PMID- 19843909
TI  - JAMA patient page. Hypertrophic cardiomyopathy.

PMID- 19843910
TI  - Successful transseptal puncture and cryoballoon pulmonary vein isolation in
      adverse anatomy: interrupted inferior caval vein and azygos continuation.

PMID- 19843911
TI  - Real-time integration of intracardiac echocardiography to facilitate atrial
      tachycardia ablation in a patient with a Senning baffle.

PMID- 19843912
TI  - Esophageal fistula formation despite esophageal monitoring and low-power
      radiofrequency catheter ablation for atrial fibrillation.

PMID- 19843913
TI  - Everything counts in large amounts: device-detected atrial high-rate arrhythmias.

PMID- 19843914
TI  - The relationship between daily atrial tachyarrhythmia burden from implantable
      device diagnostics and stroke risk: the TRENDS study.
AB  - BACKGROUND: It is unknown if brief episodes of device-detected atrial
      fibrillation (AF) increase thromboembolic event (TE) risk. METHODS AND RESULTS:
      TRENDS was a prospective, observational study enrolling patients with > or = 1
      stroke risk factor (heart failure, hypertension, age > or = 65 years, diabetes,
      or prior TE) receiving pacemakers or defibrillators that monitor atrial
      tachycardia (AT)/AF burden (defined as the longest total AT/AF duration on any
      given day during the prior 30-day period). This time-varying exposure was updated
      daily during follow-up and related to TE risk. Annualized TE rates were
      determined according to AT/AF burden subsets: zero, low (<5.5 hours [median
      duration of subsets with nonzero burden]), and high (> or = 5.5 hours). A
      multivariate Cox model provided hazard ratios including terms for stroke risk
      factors and time-varying AT/AF burden and antithrombotic therapy. Patients
      (n=2486) had at least 30 days of device data for analysis. During a mean follow
      up of 1.4 years, annualized TE risk (including transient ischemic attacks) was
      1.1% for zero, 1.1% for low, and 2.4% for high burden subsets of 30-day windows.
      Compared with zero burden, adjusted hazard ratios (95% CIs) in the low and high
      burden subsets were 0.98 (0.34 to 2.82, P=0.97) and 2.20 (0.96 to 5.05, P=0.06),
      respectively. CONCLUSIONS: The TE rate was low compared with patients with
      traditional AF with similar risk profiles. The data suggest that TE risk is a
      quantitative function of AT/AF burden. AT/AF burden > or = 5.5 hours on any of 30
      prior days appeared to double TE risk. Additional studies are needed to more
      precisely investigate the relationship between stroke risk and AT/AF burden.

PMID- 19843915
TI  - A randomized controlled trial of the efficacy and safety of electroanatomic
      circumferential pulmonary vein ablation supplemented by ablation of complex
      fractionated atrial electrograms versus potential-guided pulmonary vein antrum
      isolation guided by intracardiac ultrasound.
AB  - BACKGROUND: The study was conducted to compare relative safety and efficacy of
      pulmonary vein antrum isolation (PVAI) using intracardiac echocardiographic
      guidance and circumferential pulmonary vein ablation (CPVA) for atrial
      fibrillation (AF) using radiofrequency energy. METHODS AND RESULTS: Sixty
      patients (81% men; 81% paroxysmal; age, 56+/-8 years) failing 2+/-1
      antiarrhythmic drugs were randomly assigned to undergo CPVA (n=30) or PVAI (n=30)
      at 5 centers between December 2004 and October 2007. CPVA patients had circular
      lesions placed at least 1 cm outside of the veins. Ipsilateral veins were ablated
      en block with the end point of disappearance of potentials within the circular
      lesion. Left atrial roof line and mitral isthmus line were ablated without
      verification of block. For patients in AF postablation or with AF induced with
      programmed stimulation, complex fractionated electrograms were mapped and ablated
      to the end point of AF termination or disappearance of complex fractionated
      electrograms. PVAI did not include complex fractionated electrogram ablation.
      Esophageal temperature was monitored and kept within 2 degrees C of baseline or
      under 39 degrees C. Success was defined as absence of atrial tachyarrhythmias
      (AF/AT) off antiarrhythmic drugs. There was no difference between CPVA and PVAI
      regarding to baseline variables, catheter used, duration of the procedure, or RF
      delivery. Fluoroscopy time was longer with PVAI (54+/-17 minutes versus 77+/-18
      minutes, P=0.0001). No significant complications occurred in either arm. PVAI was
      more likely to achieve control of AF/AT off antiarrhythmic drugs (57% versus 27%,
      P=0.02) at 2+/-1 years of follow-up. CONCLUSIONS: A single PVAI procedure is more
      likely to result in freedom from AF/AT off antiarrhythmic drugs than CPVA
      supplemented by complex fractionated electrogram ablation in select patients.

PMID- 19843916
TI  - Relationship of paroxysmal atrial tachyarrhythmias to volume overload: assessment
      by implanted transpulmonary impedance monitoring.
AB  - BACKGROUND: Clinical experience suggests that atrial tachyarrhythmias (ATs) are a
      frequent comorbidity in heart failure patients with left ventricular systolic
      dysfunction and that volume overload may increase AT susceptibility. However,
      substantiating this apparent relationship in free-living patients is difficult.
      Recently, certain implantable cardioverter-defibrillators provide, by measuring
      transpulmonary electric bioimpedance, an index of intrathoracic fluid status
      (OptiVol index [OI]). The goal of this study was to determine whether periods of
      greater intrathoracic fluid congestion (as detected by OI) correspond with
      increased AT event frequency. METHODS AND RESULTS: This analysis retrospectively
      assessed the relation between AT events and OI estimate of volume overload in
      patients with left ventricular systolic dysfunction and OI-capable implantable
      cardioverter-defibrillators. OI values were stratified into 3 levels: group 1,
      <40; group 2, 40 to 60; and group 3, >60. An OI threshold-crossing event was
      defined as OI > or = 60, a value previously associated with clinically
      significant volume overload. Findings in 59 patients (mean left ventricular
      ejection fraction, 24%) with 225 follow-up visits (mean, 3.8 visits per patient)
      were evaluated. AT prevalence was 73%. AT frequency (percent of patients visits
      with at least 1 episode of AT since previous device interrogation) was greater in
      group 3 versus group 1 (P=0.0342). Finally, in terms of temporal sequence, AT
      episodes preceded OI threshold-crossing event in 43% of incidences, followed
      threshold-crossing event in 29%, and was simultaneous or indeterminate in the
      remainder. CONCLUSIONS: These findings not only support the view that worsening
      pulmonary congestion is associated with increased AT frequency in patients with
      left ventricular dysfunction but also suggest that AT events may be responsible
      for triggering episodic pulmonary congestion more often than previously
      suspected.

PMID- 19843917
TI  - Long-term prognosis of probands with Brugada-pattern ST-elevation in leads V1-V3.
AB  - BACKGROUND: The prognosis of patients with saddleback or noncoved type (non-type
      1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to
      clarify the long-term prognosis of probands with non-type 1 ECG and those with
      coved (type 1) Brugada-pattern ECG. METHODS AND RESULTS: A total of 330 (123
      symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation >
      or = 1 mm in leads V(1)-V(3) were divided into 2 ECG groups-type 1 (245 probands)
      and non-type 1 (85 probands)-and were prospectively followed for 48.7+/-15.0
      months. The absence of type 1 ECG was confirmed by drug provocation test and
      multiple recordings. The ratio of individuals with a family history of sudden
      cardiac death (14%) was lower than previous studies. Clinical profiles and
      outcomes were not notably different between the 2 groups (annual arrhythmic event
      rate of probands with ventricular fibrillation; type 1: 10.2%, non-type 1: 10.6%,
      probands with syncope; type 1: 0.6%, non-type 1: 1.2%, and asymptomatic probands;
      type 1: 0.5%, non-type 1: 0%). Family history of sudden cardiac death at age <45
      years and coexistence of inferolateral early repolarization with Brugada-pattern
      ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28;
      95% confidence interval, 1.42 to 7.60; P=0.005; hazard ratio, 2.66; 95%
      confidence interval, 1.06 to 6.71; P=0.03, respectively, by multivariate
      analysis), although spontaneous type 1 ECG and ventricular fibrillation
      inducibility by electrophysiological study were not reliable parameters.
      CONCLUSIONS: The long-term prognosis of probands in non-type 1 group was similar
      to that of type 1 group. Family history of sudden cardiac death and the presence
      of early repolarization were predictors of poor outcome in this study, which
      included only probands with Brugada-pattern ST-elevation.

PMID- 19843918
TI  - Atrial arrhythmias after lung transplantation: epidemiology, mechanisms at
      electrophysiology study, and outcomes.
AB  - BACKGROUND: Atrial arrhythmias (AAs) including atrial fibrillation (AF) and
      atrial tachycardia (AT) are often observed after cardiothoracic surgery. Our aim
      was to evaluate the prevalence and mechanism of AAs after lung transplantation.
      METHODS AND RESULTS: All patients (n=127) after bilateral sequential lung
      transplantation followed at our institution over 20 years were included. All
      patients received postoperative rhythm monitoring and clinic visits with ECG at
      1, 3, 6, and 12 months, or as needed. AAs occurred in 40 of 127 (31.5%) patients
      over 4.2+/-4.1 years. AA prevalence at postoperation and 1, 3, 6, 12, and >12
      months was 24%, 11%, 3%, 2%, 4%, and 11%, respectively. Early AAs were
      predominantly AF, whereas all AAs >12 months were AT. Time to first AF versus AT
      was 11+/-9 versus 1485+/-2462 days (P=0.09). Male sex, age, and preoperative AA
      predicted any early (<3 months) AA but did not predict late AA. Early AA did not
      predict late AT. In 4 patients with drug-resistant AT, electrophysiology studies
      found AT involving the pulmonary vein/left atrium anastomoses in 3 patients,
      including donor-to-recipient conduction in 1, border zone macroreentry in 2, and
      cavotricuspid isthmus dependent flutter in 1; all patients were successfully
      treated with ablation. CONCLUSIONS: AAs after lung transplantation are common.
      Although AF is common early, AF is rare after healing of left atrial incisions,
      which probably result in surgical pulmonary vein isolation with rare exception.
      This raises the question of whether additional surgical or ablation lines at the
      time of lung transplantation would prevent late AA.

PMID- 19843919
TI  - Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT
      syndrome.
AB  - BACKGROUND: Drugs with I(Kr)-blocking action cause secondary long-QT syndrome.
      Several cases have been associated with mutations of genes coding cardiac ion
      channels, but their frequency among patients affected by drug-induced long-QT
      syndrome (dLQTS) and the resultant molecular effects remain unknown. METHODS AND
      RESULTS: Genetic testing was carried out for long-QT syndrome-related genes in 20
      subjects with dLQTS and 176 subjects with congenital long-QT syndrome (cLQTS);
      electrophysiological characteristics of dLQTS-associated mutations were analyzed
      using a heterologous expression system with Chinese hamster ovary cells together
      with a computer simulation model. The positive mutation rate in dLQTS was similar
      to cLQTS (dLQTS versus cLQTS, 8 of 20 [40%] versus 91 of 176 [52%] subjects,
      P=0.32). The incidence of mutations was higher in patients with torsades de
      pointes induced by nonantiarrhythmic drugs than by antiarrhythmic drugs
      (antiarrhythmic versus others, 3 of 14 [21%] versus 5 of 6 [83%] subjects,
      P<0.05). When reconstituted in Chinese hamster ovary cells, KCNQ1 and KCNH2
      mutant channels showed complex gating defects without dominant negative effects
      or a relatively mild decreased current density. Drug sensitivity for mutant
      channels was similar to that of the wild-type channel. With the Luo-Rudy
      simulation model of action potentials, action potential durations of most mutant
      channels were between those of wild-type and cLQTS. CONCLUSIONS: dLQTS had a
      similar positive mutation rate compared with cLQTS, whereas the functional
      changes of these mutations identified in dLQTS were mild. When I(Kr)-blocking
      agents produce excessive QT prolongation (dLQTS), the underlying genetic
      background of the dLQTS subject should also be taken into consideration, as would
      be the case with cLQTS; dLQTS can be regarded as a latent form of long-QT
      syndrome.

PMID- 19843920
TI  - New ECG criteria in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
AB  - BACKGROUND: Desmosomal changes, electric uncoupling, and surviving myocardial
      bundles in fibrofatty tissue characterize arrhythmogenic right ventricular
      dysplasia/cardiomyopathy (ARVD/C). Resultant activation delay is pivotal for
      reentry and thereby ventricular tachycardia (VT). Current task force criteria
      (TFC) for diagnosis have limited sensitivity. The aim of this study was to assess
      the diagnostic value of additional criteria on activation delay and VT to improve
      identification of affected individuals. METHODS AND RESULTS: ECG criteria were
      studied, while off drugs, in 50 index patients with proven ARVD/C according to
      TFC (TFC > or = 4 points) and 33 patients with probable ARVD/C (TFC 3 points, or
      TFC3), being 21 index patients and 12 family members of proven ARVD/C patients.
      Newly proposed additional criteria are (1) prolonged terminal activation duration
      in V(1)-V(3), an indicator of activation delay, (2) VT with left bundle-branch
      block morphology and superior axis, and (3) multiple VT morphologies. All index
      patients were screened for mutations in ARVD/C-related genes encoding desmosomal
      proteins. Altogether, 23 of 33 (70%) TFC3 patients fulfilled ARVD/C diagnosis
      when newly proposed criteria were applied additionally to current TFC. VT with
      left bundle-branch block morphology and superior axis or multiple VT morphologies
      were recorded in 12 and 9 of 33 TFC3 patients, respectively, all being index
      patients. When applying prolonged terminal activation duration additionally to
      TFC on depolarization/conduction abnormalities, 14 (42%) TFC3 patients fulfilled
      ARVD/C diagnosis. Results were not significantly different between mutation
      carriers and noncarriers. CONCLUSIONS: Adding the newly proposed criteria to
      current TFC for ARVD/C will improve identification of affected individuals
      importantly, independent of outcome of DNA analyses.

PMID- 19843921
TI  - Exercise-induced ECG changes in Brugada syndrome.
AB  - BACKGROUND: Ventricular arrhythmia occurrence during exercise is reported in
      Brugada syndrome (BrS). Accordingly, experimental studies suggest that BrS-linked
      SCN5A mutations reduce sodium current more at fast heart rates. Yet, the effects
      of exercise on the BrS ECG phenotype have not been studied. We aimed to assess
      ECG responses to exercise in BrS and determine whether these responses are
      affected by the presence of an SCN5A mutation. METHODS AND RESULTS: ECGs at
      baseline, at peak exercise, and during recovery were analyzed from 35 male
      control subjects, 25 BrS men without SCN5A mutation (BrS(SCN5A)(-)), and 25 BrS
      men with SCN5A mutation (BrS(SCN5A+); 15 with missense mutation and 10 with
      mutation leading to premature truncation of the protein). No differences existed
      in clinical phenotype between BrS groups. At baseline, BrS(SCN5A)(-) and
      BrS(SCN5A+) patients had lower heart rates, wider QRS, shorter QT(c), and higher
      peak J-point amplitudes than control subjects; BrS(SCN5A+) patients also had
      longer PR than BrS(SCN5A)(-) and control subjects. Exercise resulted in PR
      shortening in all groups, more QRS widening in BrS(SCN5A+) than in BrS(SCN5A)(-)
      and control subjects(,) and less QT shortening in BrS(SCN5A)(-) and BrS(SCN5A+)
      than in control subjects. The latter resulted in QT(c) shortening in control
      subjects but QT(c) prolongation in BrS(SCN5A)(-) and BrS(SCN5A+). Finally, the
      increase in peak J-point amplitude during exercise was similar in all 3 groups
      but resulted in a coved-type pattern only in BrS(SCN5A)(-) and BrS(SCN5A+).
      CONCLUSIONS: Exercise aggravated the ECG phenotype in BrS. The presence of an
      SCN5A mutation was associated with further conduction slowing at fast heart
      rates. Possible mechanisms that may explain the observed ECG changes are
      discussed.

PMID- 19843923
TI  - Predicting ventricular arrhythmias in patients with ischemic heart disease:
      clinical application of the ECG-derived QRS-T angle.
AB  - BACKGROUND: In patients with primary prevention implantable cardioverter
      defibrillators (ICDs), the incidence of life-threatening ventricular arrhythmias
      resulting in ICD therapy is relatively low, prompting for better risk
      stratification. The aim of this study was to assess the value of the QRS-T angle
      for prediction of ICD therapy and mortality in primary prevention patients with
      ischemic heart disease. METHODS AND RESULTS: ICD patients (n=412, 361 men; age,
      63+/-11 years) with ischemic heart disease and a left ventricular ejection
      fraction < or = 40% were included. After device implantation, the occurrence of
      appropriate ICD therapy and mortality was noted. A survival analysis was
      performed comparing patients with a planar QRS-T angle < or = 90 degrees (n=124,
      30%) with patients with a planar QRS-T angle >90 degrees before device
      implantation. Furthermore, patients with a spatial QRS-T angle < or = 100 degrees
      (n=56, 14%) were compared with patients with a spatial QRS-T angle >100 degrees ,
      before implantation. For patients with a planar QRS-T angle >90 degrees as
      compared with < or = 90 degrees , the adjusted hazard ratio for the occurrence of
      appropriate device therapy was 2.4 (95% CI, 1.1 to 5.2); a spatial QRS-T angle
      >100 degrees was associated with an adjusted hazard ratio of 7.3 (95% CI, 1.0 to
      53.8). Furthermore, a spatial QRS-T angle < or = 100 degrees exhibited a positive
      predictive value of 98% (95% CI, 95 to 100) for the prediction of an appropriate
      therapy-free follow-up. CONCLUSIONS: A wide QRS-T angle is a strong predictor of
      appropriate device therapy in primary prevention ICD recipients with ischemic
      heart disease. Furthermore, a spatial QRS-T angle < or = 100 degrees might be of
      value in the identification of patients in whom, although currently indicated,
      ICD treatment should be reconsidered.

PMID- 19843922
TI  - Protein kinase A-dependent biophysical phenotype for V227F-KCNJ2 mutation in
      catecholaminergic polymorphic ventricular tachycardia.
AB  - BACKGROUND: KCNJ2 encodes Kir2.1, a pore-forming subunit of the cardiac inward
      rectifier current, I(K1). KCNJ2 mutations are associated with Andersen-Tawil
      syndrome and catecholaminergic polymorphic ventricular tachycardia. The aim of
      this study was to characterize the biophysical and cellular phenotype of a KCNJ2
      missense mutation, V227F, found in a patient with catecholaminergic polymorphic
      ventricular tachycardia. METHODS AND RESULTS: Kir2.1-wild-type (WT) and V227F
      channels were expressed individually and together in Cos-1 cells to measure I(K1)
      by voltage clamp. Unlike typical Andersen-Tawil syndrome-associated KCNJ2
      mutations, which show dominant negative loss of function, Kir2.1WT+V227F
      coexpression yielded I(K1) indistinguishable from Kir2.1-WT under basal
      conditions. To simulate catecholamine activity, a protein kinase A (PKA)
      stimulating cocktail composed of forskolin and 3-isobutyl-1-methylxanthine was
      used to increase PKA activity. This PKA-simulated catecholaminergic stimulation
      caused marked reduction of outward I(K1) compared with Kir2.1-WT. PKA-induced
      reduction in I(K1) was eliminated by mutating the phosphorylation site at serine
      425 (S425N). CONCLUSIONS: Heteromeric Kir2.1-V227F and WT channels showed an
      unusual latent loss of function biophysical phenotype that depended on PKA
      dependent Kir2.1 phosphorylation. This biophysical phenotype, distinct from
      typical Andersen-Tawil syndrome mutations, suggests a specific mechanism for PKA
      dependent I(K1) dysfunction for this KCNJ2 mutation, which correlates with
      adrenergic conditions underlying the clinical arrhythmia.

PMID- 19843924
TI  - Right-to-left ventricular diastolic delay in chronic thromboembolic pulmonary
      hypertension is associated with activation delay and action potential
      prolongation in right ventricle.
AB  - BACKGROUND: Delayed left ventricle (LV)-to-right ventricle (RV) peak shortening
      results in cardiac output reduction in patients with chronic thromboembolic
      hypertension (CTEPH) and other types of pulmonary arterial hypertension. Why the
      synchrony between LV and RV is lost is unknown. We hypothesized that RV
      electrophysiological remodeling, notably, conduction slowing and action potential
      prolongation, contribute to this loss in synchrony. METHODS AND RESULTS: We
      conducted epicardial mapping during pulmonary endarterectomy in 26 patients with
      CTEPH and compared these findings with clinical, hemodynamic, and
      echocardiographic variables. We consecutively placed a multielectrode grid on the
      epicardium of the RV free wall and LV lateral wall. These regions corresponded to
      RV and LV areas where echocardiographic Doppler sample volumes were placed to
      measure RV-to-LV diastolic interventricular delay. RV and LV epicardial action
      potential duration was assessed by measuring activation-recovery interval. Onset
      of diastolic relaxation of RV free wall with respect to LV lateral wall
      (diastolic interventricular delay) was delayed by 38+/-31 ms in patients with
      CTEPH versus -12+/-13 ms in control subjects (P<0.001), because, in patients with
      CTEPH, RV completed electric activation later than LV (65+/-20 versus 44+/-7 ms,
      P<0.001) and epicardial action potential duration, as assessed by activation
      recovery interval measurement, was longer in RV free wall than in LV lateral wall
      (253+/-29 versus 240+/-22 ms, P<0.001). CONCLUSIONS: Additive effects of
      electrophysiological changes in RV, notably, conduction slowing and action
      potential prolongation, assessed by epicardial activation-recovery interval,
      contribute to diastolic interventricular delay in patients with CTEPH.

PMID- 19843925
TI  - Short-term memory and restitution during ventricular fibrillation in human
      hearts: an in vivo study.
AB  - BACKGROUND: Action potential duration (APD) variation is an important determinant
      of wave break and reentry. The determinants of APD variability during early
      ventricular fibrillation (VF) in myopathic human hearts have not been studied.
      The objective of this study was to study the role of APD restitution and short
      term cardiac memory on variation in human VF. METHODS AND RESULTS: The study
      consisted of 7 patients (67+/-9 years old) with ejection fraction <35%.
      Monophasic action potentials were recorded from the right and/or left ventricular
      septum during VF. APD(60/90) was measured in sinus beat preceding induction of
      VF, and its amplitude was used to define 60%/90% repolarization in VF. The
      monophasic action potential upstroke (dV/dt(max)) was used to characterize local
      excitability. Simple linear regression showed that variability in APD(n60) was
      determined by APD/diastolic interval restitution (R(2)=0.48, P<0.0001) and short
      term memory (APD(60) n-1, n-2, n-3, n-4; R(2)=0.55, 0.40, 0.33, and 0.27
      respectively; P<0.001). Using multiple stepwise regression, short-term memory and
      restitution accounted for 62% of variance in APD(60) (P<0.001). Individually,
      memory effect had the greatest contribution to APD variability (R(2)=0.55,
      P<0.0001). CONCLUSIONS: In early human VF, short-term memory and APD/diastolic
      interval restitution explain most of the APD variability, with memory effects
      predominating. This suggests that in early human VF, short-term cardiac memory
      may provide a novel therapeutic target to modulate progression of VF in myopathic
      patients.

PMID- 19843926
TI  - Left ventricular septal and left ventricular apical pacing chronically maintain
      cardiac contractile coordination, pump function and efficiency.
AB  - BACKGROUND: Conventional right ventricular (RV) apex pacing can lead to adverse
      clinical outcome associated with asynchronous activation and reduced left
      ventricular (LV) pump function. We investigated to what extent alternate RV
      (septum) and LV (septum, apex) pacing sites improve LV electric activation,
      mechanics, hemodynamic performance, and efficiency over 4 months of pacing.
      METHODS AND RESULTS: After AV nodal ablation, mongrel dogs were randomized to
      receive 16 weeks of VDD pacing at the RV apex, RV septum, LV apex, or LV septum
      (transventricular septal approach). Electric activation maps (combined epicardial
      contact and endocardial noncontact) showed that RV apical and RV septal pacing
      induced significantly greater electric desynchronization than LV apical and LV
      septal pacing. RV apex and RV septal pacing also significantly increased
      mechanical dyssynchrony, discoordination (MRI tagging) and blood flow
      redistribution (microspheres) and reduced LV contractility, relaxation, and
      myocardial efficiency (stroke work/myocardial oxygen consumption). In contrast,
      LV apical and LV septal pacing did not significantly alter these parameters as
      compared with the values during intrinsic conduction. At 16 weeks, acute
      intrasubject comparison showed that single-site LV apical and LV septal pacing
      generally resulted in similar or better contractility, relaxation, and efficiency
      as compared with acute biventricular pacing. CONCLUSIONS: Acute and chronic LV
      apical and LV septal pacing maintain regional cardiac mechanics, contractility,
      relaxation, and efficiency near native levels, whereas RV apical or RV septal
      pacing diminish these variables. Acute LV apical and LV septal pacing tend to
      maintain or improve contractility and efficiency compared with biventricular
      pacing.

PMID- 19843927
TI  - Left ventricular endocardial pacing improves resynchronization therapy in canine
      left bundle-branch hearts.
AB  - BACKGROUND: We investigated the benefits of the more physiological activation
      achieved by left ventricular (LV) endocardial pacing (ENDO) as compared with
      conventional epicardial (EPI) LV pacing in cardiac resynchronization therapy.
      METHODS AND RESULTS: In 8 anesthetized dogs with experimental left bundle-branch
      block, pacing leads were positioned in the right atrium, right ventricle, and at
      8 paired (EPI and ENDO) LV sites. Systolic LV pump function was assessed as
      LVdP/dtmax and stroke work and diastolic function as LVdP/dtmin. Electrical
      activation and dispersion of repolarization were determined from 122 epicardial
      and endocardial electrodes and from analysis of the surface ECG. Overall, ENDO
      biventricular (BiV) pacing more than doubled the degree of electrical
      resynchronization and increased the benefit on LVdP/dtmax and stroke work by 90%
      and 50%, respectively, as compared with EPI-BiV pacing. During single-site LV
      pacing, the range of AV intervals with a >10% increase in LV resynchronization
      (79+/-31 versus 32+/-24 ms, P<0.05) and LVdP/dtmax (92+/-29 versus 63+/-39 ms)
      was significantly longer for ENDO than for EPI pacing. EPI-BiV but not ENDO-BiV
      pacing created a significant (40+/-21 ms) transmural dispersion of
      repolarization. CONCLUSIONS: Data from this acute animal study indicate that the
      use of an endocardial LV pacing electrode may increase the efficacy of
      resynchronization therapy as compared with conventional epicardial
      resynchronization therapy.

PMID- 19843928
TI  - New pharmacological agents for arrhythmias.

PMID- 19843929
TI  - Comment on "Critical roles of NK and CD8+ T cells in central nervous system
      listeriosis".

PMID- 19843930
TI  - Establishing anergy as a bona fide in vivo mechanism of B cell tolerance.

PMID- 19843931
TI  - Altered immunoglobulin expression and functional silencing of self-reactive B
      lymphocytes in transgenic mice.

PMID- 19843932
TI  - 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of
      inflammatory cytokines and promote development of regulatory T cells expressing
      CTLA-4 and FoxP3.
AB  - The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has
      potent immunomodulatory properties that have promoted its potential use in the
      prevention and treatment of infectious disease and autoimmune conditions. A
      variety of immune cells, including macrophages, dendritic cells, and activated T
      cells express the intracellular vitamin D receptor and are responsive to
      1,25(OH)(2)D(3.) Despite this, how 1,25(OH)(2)D(3) regulates adaptive immunity
      remains unclear and may involve both direct and indirect effects on the
      proliferation and function of T cells. To further clarify this issue, we have
      assessed the effects of 1,25(OH)(2)D(3) on human CD4(+)CD25(-) T cells. We
      observed that stimulation of CD4(+)CD25(-) T cells in the presence of
      1,25(OH)(2)D(3) inhibited production of proinflammatory cytokines including IFN-
      gamma, IL-17, and IL-21 but did not substantially affect T cell division. In
      contrast to its inhibitory effects on inflammatory cytokines, 1,25(OH)(2)D(3)
      stimulated expression of high levels of CTLA-4 as well as FoxP3, the latter
      requiring the presence of IL-2. T cells treated with 1,25(OH)(2)D(3) could
      suppress proliferation of normally responsive T cells, indicating that they
      possessed characteristics of adaptive regulatory T cells. Our results suggest
      that 1,25(OH)(2)D(3) and IL-2 have direct synergistic effects on activated T
      cells, acting as potent anti-inflammatory agents and physiologic inducers of
      adaptive regulatory T cells.

PMID- 19843933
TI  - CD4+ T cells and Lactobacillus casei control relapsing colitis mediated by CD8+ T
      cells.
AB  - Evidence that CD4(+) regulatory T cells can control Ag-specific CD8(+) T cell
      mediated colitis in immunocompetent mice is poorly documented. To examine the
      potential of CD4(+) T cells to control colitis, we used our model of CD8(+) T
      cell-mediated colitis induced by intracolonic sensitization followed by challenge
      with the hapten 2,4-dinitrobenzene sulfonic acid. The defect of CD4(+) T cells in
      MHC class II-deficient (Abeta(degrees/degrees)) mice allowed priming of 2,4
      dinitrobenzene sulfonic acid-specific IFN-gamma-producing CD8 colitogenic
      effectors and development of colitis in the otherwise resistant C57BL/6 strain.
      Cotransfer experiments in RAG2(degrees/degrees) mice and ex vivo studies showed
      that CD4(+)CD25(+) T cells completely prevented CD8(+) T cell-mediated colitis
      and controlled CD8(+) T cell activation, respectively. In the susceptible BALB/c
      strain, Ab depletion revealed that lack of CD4(+) regulatory T cells resulted in
      1) acute colitis elicited by a suboptimal dose of hapten challenge and 2) more
      severe relapsing episodes of colitis induced by effector/memory CD8(+) T cell
      mediated colitis at an optimal dose of hapten challenge, even when CD4 depletion
      was performed just before the second challenge. Oral administration of the
      probiotic strain Lactobacillus casei DN-114 001 alleviated colitis and increased
      the suppressive function of Foxp3(+)CD4(+) regulatory T cells of colon lamina
      propria. These data demonstrate that CD4(+) regulatory T cells exert a protective
      effect on colitis by controlling colitogenic effector/memory CD8(+) T cells
      during the effector (symptomatic) phase of acute and relapsing colitis,
      respectively. Probiotics with natural adjuvant effects on mucosal regulatory T
      cells may represent a valuable approach to alleviate the colitogenic effect of
      Tc1-type CD8(+) effectors.

PMID- 19843934
TI  - A2A adenosine receptor may allow expansion of T cells lacking effector functions
      in extracellular adenosine-rich microenvironments.
AB  - Immunosuppressive signaling via the A2A adenosine receptor (A2AR) provokes a
      mechanism that protects inflamed tissues from excessive damage by immune cells.
      This mechanism is desirable not only for preventing uncontrolled tissue
      destruction by overactive immune responses, but also for protecting tumor tissues
      from antitumor immune responses. In aforementioned circumstances, T cell priming
      may occur in an environment containing high concentrations of extracellular
      adenosine. To examine qualitative changes in T cells activated in the presence of
      adenosine, we asked whether different functional responses of T cells are equally
      susceptible to A2AR agonists. In this study, we demonstrate that A2AR signaling
      during T cell activation strongly inhibited development of cytotoxicity and
      cytokine-producing activity in T cells, whereas the inhibition of T cell
      proliferation was only marginal. Both CD8(+) and CD4(+) T cells proliferated well
      in the presence of A2AR agonists, but their IFN-gamma-producing activities were
      susceptible to inhibition by cAMP-elevating A2AR. Importantly, the impaired
      effector functions were maintained in T cells even after removal of the A2AR
      agonist, reflecting T cell memory of the immunoregulatory effect of adenosine.
      Thus, although the adenosine-rich environment may allow for the expansion of T
      cells, the functional activation of T cells may be critically impaired. This
      physiological mechanism could explain the inefficiency of antitumor T cells in
      the tumor microenvironment.

PMID- 19843935
TI  - Phenotypical characterization of human Th17 cells unambiguously identified by
      surface IL-17A expression.
AB  - Th17 cells are involved in the defense against bacteria and fungi and play a
      prominent role in the pathogenesis of autoimmune diseases, but research on human
      Th17 cells is hindered due to the lack of a surface marker. In this study, we
      report that a subset of human and mouse CD4(+) T cells as well as human Th17 T
      cell clones express IL-17A on their surface upon stimulation. Correlation of
      surface IL-17A expression with intracellular IL-17A production and with RORgammat
      mRNA expression identified surface IL-17A as a specific marker for human and
      mouse Th17 cells. Phenotype characterization of ex vivo CD4(+) IL-17A(+) cells
      showed that the chemokines CCR6 and CCR4, costimulatory molecules, as well as CD2
      and CD49d were more prominently expressed on these cells than in surface IL-17A(
      ) cells, supporting the concept of Th17 cells as a potent inflammatory effector
      subtype. In addition, we generated human Th1, Th1/17 (producing both IFN-gamma
      and IL-17A), and Th17 T cell clones based on single cell sorting of surface IL
      17A(-), IL-17A(int), and IL-17A(high) CD4(+) T cells, respectively, and showed
      the plasticity of the double producing clones to the cytokine milieu. The
      identification of surface IL-17A as a marker for Th17 cells should facilitate
      research on this subset.

PMID- 19843936
TI  - FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell
      receptor-mediated signaling.
AB  - A polymorphism that up-regulates the expression of Fc receptor-like 3 (FCRL3)
      gene has recently been described as predisposing for several human autoimmune
      diseases. FCRL3 is preferentially expressed on B cells and is unique in
      displaying both an ITAM and an ITIM in the cytosolic domain, suggesting signaling
      functions. Herein, we show that FCRL3 potentially inhibits BCR-mediated
      signaling, using murine FcgammaRIIB/human FCRL3 chimeric protein. Coligation of
      the chimeric protein with BCR leads to phosphorylation of tyrosine residues in
      the cytosolic domain. This coligation inhibits cell tyrosine phosphorylation and
      calcium mobilization in addition to activation-induced cell death mediated by BCR
      signaling. Mutational analysis showed the tyrosine residues in two potential
      ITIMs at 662 and 692 offer the main contributions to this inhibition, which is
      further supported by strong associations of SH-2 domain-containing phosphatases
      with the following phosphotyrosine motifs: SHIP with the ITIM-like motif at 662;
      and SHP-1 and -2 with the canonical ITIM at 692. These results, together with
      previous genetic data, suggest that augmented inhibition of BCR-mediated
      signaling by FCRL3 with the disease-risk genotype alter the activation threshold
      and promote tolerance breakdown in B cells.

PMID- 19843937
TI  - Functional expression of formyl peptide receptor family in human NK cells.
AB  - We determined the expression of the formyl peptide receptor (FPR) family and the
      functional roles of the FPR family in NK cells. All tested human NK cells express
      two members of the FPR family (FPR1 and FPR2). The expression of FPR3 was noted
      to occur in a donor-specific manner. The stimulation of NK cells with FPR family
      selective agonists (fMLF (N-formyl-Met-Leu-Phe), MMK-1, F2L, and WKYMVm (Trp-Lys
      Tyr-Met-Val-d-Met)) elicited cytolytic activity in resting NK cells, but not in
      IL-2-activated NK cells; the cytolytic activity was not inhibited by pertussis
      toxin. The FPR family agonists also stimulated chemotactic migration of IL-2
      activated NK cells, but not resting NK cells; the chemotactic migration was
      completely inhibited by pertussis toxin. WKYMVm stimulates ERK, p38 MAPK, and JNK
      activities in both resting and IL-2-activated NK cells. WKYMVm-induced
      chemotactic migration was partially inhibited by PD98059 (2'-amino-3'
      methoxyflavone); however, the inhibition of JNK by its selective inhibitor
      (SP600125, anthra[1,9-cd]pyrazol-6(2H)-one) dramatically inhibited the WKYMVm
      induced cytolytic activity. Furthermore, WKYMVm-induced chemotactic migration and
      cytolytic activity were partly inhibited by FPR family-selective antagonists
      (cyclosporin H and WRWWWW). Taken together, our findings indicate that human NK
      cells express functional members of the FPR family, and in turn the activation of
      the three members of the FPR receptor family elicit cytolytic activity in NK
      cells, thus suggesting that the receptors are potentially important therapeutic
      targets for the modulation of NK cell-mediated immune responses.

PMID- 19843938
TI  - Epidermal Langerhans cells are not required for UV-induced immunosuppression.
AB  - UV light can be highly beneficial in the treatment of skin disorders such as
      psoriasis. It is thought to cause immunosuppression by depleting or altering the
      function of epidermal Langerhans cells (LC). Our previous studies identified a
      novel langerin(+) dendritic cell in the dermis, distinct from LC in phenotype,
      circulation, and function. In this study, we determined the role of LC and dermal
      langerin(+) cells in UV suppression. UV light suppressed the CD8 T cell response
      to both contact hypersensitivity and epicutaneous protein immunization, and
      resulted in a dramatically altered phenotype of LC. UV light did not alter early
      CD8 T cell activation in the lymph nodes, but rather reduced CD8 T cell expansion
      at later time points. We found that dermal langerin(+) cells, but not LC, were
      essential for the CD8 T cell response. Furthermore, in the selective absence of
      LC, UV light still caused suppression of both CD8 T cell expansion and contact
      hypersensitivity.

PMID- 19843939
TI  - The activation threshold of CD4+ T cells is defined by TCR/peptide-MHC class II
      interactions in the thymic medulla.
AB  - Immature thymocytes that are positively selected based upon their response to
      self-peptide-MHC complexes develop into mature T cells that are not overtly
      reactive to those same complexes. Developmental tuning is the active process
      through which TCR-associated signaling pathways of single-positive thymocytes are
      attenuated to respond appropriately to the peptide-MHC molecules that will be
      encountered in the periphery. In this study, we explore the mechanisms that
      regulate the tuning of CD4(+) single-positive T cells to MHC class II encountered
      in the thymic medulla. Experiments with murine BM chimeras demonstrate that
      tuning can be mediated by MHC class II expressed by either thymic medullary
      epithelial cells or thymic dendritic cells. Tuning does not require the
      engagement of CD4 by MHC class II on stromal cells. Rather, it is mediated by
      interactions between MHC class II and the TCR. To understand the molecular
      changes that distinguish immature hyperactive T cells from tuned mature CD4(+) T
      cells, we compared their responses to TCR stimulation. The altered response of
      mature CD4 single-positive thymocytes is characterized by the inhibition of ERK
      activation by low-affinity self-ligands and increased expression of the
      inhibitory tyrosine phosphatase SHP-1. Thus, persistent TCR engagement by peptide
      MHC class II on thymic medullary stroma inhibits reactivity to self-Ags and
      prevents autoreactivity in the mature repertoire.

PMID- 19843940
TI  - A herceptin-based chimeric antigen receptor with modified signaling domains leads
      to enhanced survival of transduced T lymphocytes and antitumor activity.
AB  - To generate chimeric Ag receptors (CARs) for the adoptive immunotherapy of cancer
      patients with ErbB2-expressing tumors, a single-chain Ab derived from the
      humanized mAb 4D5 Herceptin (trastuzumab) was initially linked to T cell
      signaling domains derived from CD28 and the CD3zeta to generate a CAR against
      ErbB2. Human PBLs expressing the 4D5 CAR demonstrated Ag-specific activities
      against ErbB2(+) tumors. However, a gradual loss of transgene expression was
      noted for PBLs transduced with this 4D5 CAR. When the CD3zeta signaling domain of
      the CAR was truncated or mutated, loss of CAR expression was not observed,
      suggesting that the CD3zeta signaling caused the transgene decrease, which was
      supported by the finding that T cells expressing 4D5 CARs with CD3zeta ITAM
      mutations were less prone to apoptosis. By adding 4-1BB cytoplasmic domains to
      the CD28-CD3zeta signaling moieties, we found increased transgene persistence in
      4D5 CAR-transduced PBLs. Furthermore, constructs with 4-1BB sequences
      demonstrated increased cytokine secretion and lytic activity in 4D5 CAR
      transduced T cells. More importantly, PBLs expressing this new version of the 4D5
      CAR could not only efficiently lyse the autologous fresh tumor digests, but they
      could strongly suppress tumor growth in a xenogenic mouse model.

PMID- 19843941
TI  - Fas apoptosis inhibitory molecule expression in B cells is regulated through IRF4
      in a feed-forward mechanism.
AB  - Fas apoptosis inhibitory molecule (FAIM) was originally cloned as an inhibitor of
      Fas-mediated apoptosis in B cells that has been reported to affect multiple cell
      types. Recently, we found that FAIM enhances CD40L-mediated signal transduction,
      including induction of IFN regulatory factor (IRF)4, in vitro and augments plasma
      cell production in vivo. These results have keyed interest in the regulation of
      FAIM expression, about which little is known. Here, we show that Faim is
      regulated by IRF4. The Faim promoter contains three IRF binding sites, any two of
      which promote Faim expression. Faim promoter activity is lost following mutation
      of all three IRF binding sites, whereas activity of the full promoter is enhanced
      by concurrent expression of IRF4. In stimulated primary B cells, IRF4 expression
      precedes FAIM expression, IRF4 binds directly to the Faim promoter, and loss of
      IRF4 results in the failure of stimulated Faim up-regulation. Finally, FAIM is
      preferentially expressed in germinal center B cells. Taken together, these
      results indicate that FAIM expression is regulated through IRF4 and that this
      most likely occurs as part of germinal center formation. Because FAIM enhances
      CD40-induced IRF4 expression in B cells, these results suggest that induction of
      FAIM initiates a positive reinforcing (i.e., feed-forward) system in which IRF4
      expression is both enhanced by FAIM and promotes FAIM expression.

PMID- 19843942
TI  - c-Myb is required for pro-B cell differentiation.
AB  - The c-Myb transcription factor is required for normal adult hematopoiesis.
      However, the embryonic lethality of Myb-null mutations has been an impediment to
      identifying roles for c-Myb during lymphocyte development. We have used tissue
      specific inactivation of the Myb locus in early progenitor cells to demonstrate
      that c-Myb is absolutely required for the differentiation of CD19(+) B-lineage
      cells and B cell differentiation is profoundly blocked beyond the pre-pro-B cell
      stage in Myb(f/f) Mb1-cre mice. We demonstrate that c-Myb is required for the
      intrinsic survival of CD19(+) pro-B cells as well as the proper expression of the
      alpha-chain of the IL-7 receptor (CD127) and Ebf1. However, survival of c-Myb
      deficient CD19(+) pro-B cells cannot be rescued by transduction with CD127
      producing retrovirus, suggesting that c-Myb controls a survival pathway
      independent of CD127. Furthermore, c-Myb-deficient progenitor cells inefficiently
      generate CD19(+) B-lineage cells during stromal cell culture but this process can
      be partially rescued with exogenous Ebf1. Thus, c-Myb does not appear to be
      required for commitment to B cell differentiation but is crucial for B cell
      differentiation to the CD19(+) pro-B cell stage as well as survival of CD19(+)
      pro-B cells. Surprisingly, forced c-Myb expression in lymphoid-primed multipotent
      progenitors favors differentiation toward the myeloid lineage, suggesting that
      proper c-Myb expression is crucial for B-lineage development.

PMID- 19843943
TI  - Thalidomide inhibits activation of caspase-1.
AB  - Thalidomide is an efficient anti-inflammatory and anti-angiogenic drug, but its
      therapeutic use is problematic due to a strong teratogenic activity.
      Nevertheless, thalidomide was approved for the treatment of inflammatory skin
      diseases and certain types of cancer, and it is extensively tested for several
      other indications. Recently, we demonstrated that active caspase-1, whose
      activation is dependent on inflammasome complexes, is required for unconventional
      protein secretion of proinflammatory cytokines such as IL-1 and of the
      proangiogenic fibroblast growth factor 2. In this study, we show that
      pharmacological doses of thalidomide strongly reduced the secretion of both
      proteins. Thalidomide-treated cells also released less of other leaderless
      proteins, which require caspase-1 activity for their secretion. In line with
      these findings, the drug inhibited activation and activity of caspase-1 in
      cultured cells but not in vitro. The latter finding suggests that the
      pharmacological activity is exerted by a metabolite of the drug. The anti
      inflammatory activity of thalidomide was also mediated via caspase-1 in mice.
      These findings represent a novel mechanism by which thalidomide exerts its
      pharmacological activity and suggest that inhibition of the activity of IL-1
      might represent a novel strategy to substitute thalidomide.

PMID- 19843944
TI  - Common gamma-chain-dependent signals confer selective survival of eosinophils in
      the murine small intestine.
AB  - Eosinophils are potent effector cells that are recruited to sites of
      inflammation. However, in some tissues, in particular in the gastrointestinal
      tract, eosinophils constitute an abundant leukocyte population also under
      homeostatic conditions. The lack of suitable isolation protocols restricted the
      analysis of these cells to histological assessment of cell numbers while
      important aspects of their phenotype, turnover, and functions remain unresolved.
      In this study, we report a protocol that allows the quantitative isolation of
      intestinal eosinophils. We characterized small intestinal eosinophils by flow
      cytometry as SSC(high)CD11b(+)CD11c(+)CCR3(+)Siglec-F(+) cells. Intestinal
      eosinophils resembled eosinophils isolated from thymus and uterus but differed
      from eosinophils isolated from lung or blood. Eosinophils in intestine, thymus,
      and uterus showed in vivo a markedly higher life time compared with eosinophils
      present in lung and blood measured by incorporation of BrdU. This indicates that
      under steady-state conditions homeostasis of eosinophils is controlled by
      regulation of cell survival. Intestinal eosinophils are severely reduced in the
      intestines of Rag-2/common gamma-chain double-deficient mice but not Rag-2
      deficient mice, correlating with differential expression of GM-CSF and CCL11 in
      both mouse strains. Moreover, under steady-state conditions, intestinal
      eosinophils constitutively express high levels of the common gamma-chain
      transcripts compared with lung eosinophils as well as eosinophils present under
      inflammatory conditions. These observations reveal a hitherto unrecognized
      diversity in phenotypic and functional properties of eosinophils and suggest that
      tissue-specific common gamma-chain-dependent signals might profoundly affect
      eosinophil function and homeostasis.

PMID- 19843945
TI  - Constitutive expression of IDO by dendritic cells of mesenteric lymph nodes:
      functional involvement of the CTLA-4/B7 and CCL22/CCR4 interactions.
AB  - Dendritic cells (DCs) express the immunoregulatory enzyme IDO in response to
      certain inflammatory stimuli, but it is unclear whether DCs express this enzyme
      under steady-state conditions in vivo. In this study, we report that the DCs in
      mesenteric lymph nodes (MLNs) constitutively express functional IDO, which
      metabolizes tryptophan to kynurenine. In line with a previous report that
      regulatory T cells (Tregs) can induce IDO in DCs via the CTLA-4/B7 interaction, a
      substantial proportion of the MLN DCs were located in juxtaposition to Tregs,
      whereas this tendency was not observed for splenic DCs, which do not express IDO
      constitutively. When CTLA-4 was selectively deleted in Tregs, the frequency of
      IDO-expressing DCs in MLNs decreased significantly, confirming CTLA-4's role in
      IDO expression by MLN DCs. We also found that the MLN DCs produced CCL22, which
      can attract Tregs via CCR4, and that the phagocytosis of autologous apoptotic
      cells induced CCL22 expression in CCL22 mRNA-negative DCs. Mice genetically
      deficient in the receptor for CCL22, CCR4, showed markedly reduced IDO expression
      in MLN-DCs, supporting the involvement of the CCL22/CCR4 axis in IDO induction.
      Together with our previous observation that MLN DCs contain much intracytoplasmic
      cellular debris in vivo, these results indicate that reciprocal interactions
      between the DCs and Tregs via both B7/CTLA-4 and CCL22/CCR4 lead to IDO induction
      in MLN DCs, which may be initiated and/or augmented by the phagocytosis of
      autologous apoptotic cells by intestinal DCs. Such a mechanism may help induce
      the specific milieu in MLNs that is required for the induction of oral tolerance.

PMID- 19843947
TI  - Human gamma delta T cells: a lymphoid lineage cell capable of professional
      phagocytosis.
AB  - Professional phagocytosis in mammals is considered to be performed exclusively by
      myeloid cell types. In this study, we demonstrate, for the first time, that a
      mammalian lymphocyte subset can operate as a professional phagocyte. By using
      confocal microscopy, transmission electron microscopy, and functional Ag
      presentation assays, we find that freshly isolated human peripheral blood
      gammadelta T cells can phagocytose Escherichia coli and 1 microm synthetic beads
      via Ab opsonization and CD16 (FcgammaRIII), leading to Ag processing and
      presentation on MHC class II. In contrast, other CD16(+) lymphocytes, i.e.,
      CD16(+)/CD56(+) NK cells, were not capable of such functions. These findings of
      distinct myeloid characteristics in gammadelta T cells strongly support the
      suggestion that gammadelta T cells are evolutionarily ancient lymphocytes and
      have implications for our understanding of their role in transitional immunity
      and the control of infectious diseases and cancer.

PMID- 19843946
TI  - Antibodies to the desmoglein 1 precursor proprotein but not to the mature cell
      surface protein cloned from individuals without pemphigus.
AB  - In pemphigus foliaceus (PF), autoantibodies against desmoglein 1 (Dsg1) cause
      blisters. Using Ab phage display, we have cloned mAbs from a PF patient. These
      mAbs, like those from a previous patient, were directed against mature Dsg1
      (matDsg1) on the cell surface of keratinocytes and precursor Dsg1 (preDsg1) in
      the cytoplasm. To determine whether individuals without pemphigus have B cell
      tolerance to Dsg1, we cloned mAbs from two patients with thrombotic
      thrombocytopenic purpura and a healthy person. We found mAbs against preDsg1, but
      not matDsg1. All but 1 of the 23 anti-preDsg1 mAbs from PF patients and those
      without PF used the VH3-09 (or closely related VH3-20) H chain gene, whereas no
      PF anti-matDsg1 used these genes. V(H) cDNA encoding anti-preDsg1 had
      significantly fewer somatic mutations than did anti-matDsg1 cDNA, consistent with
      chronic Ag-driven hypermutation of the latter compared with the former. These
      data indicate that individuals without PF do not have B cell tolerance to preDsg1
      and that loss of tolerance to matDsg1 is not due to epitope shifting of anti
      preDsg1 B cells (because of different V(H) gene usage). However, presentation of
      peptides from Dsg1 by preDsg1-specific B cells may be one step in developing
      autoimmunity in PF.

PMID- 19843948
TI  - Absence of mature peripheral B cell populations in mice with concomitant defects
      in B cell receptor and BAFF-R signaling.
AB  - Generation of mature B lymphocytes from early (T1) and late transitional (T2)
      precursors requires cooperative signaling through BCR and B cell-activating
      factor receptor 3 (BR3). Recent studies have shown that BCR signaling positively
      regulates NF-kappaB2, suggesting BCR regulation of BR3 signaling. To investigate
      the significance of signal integration from BCR and BR3 in B cell development and
      function, we crossed Btk-deficient mice (btk(-/-)), which are developmentally
      blocked between the T2 and the mature follicular B cell stage as a result of a
      partial defect in BCR signaling, and A/WySnJ mice, which possess a mutant BR3
      defective in propagating intracellular signals that results in a severely reduced
      peripheral B cell compartment, although all B cell subsets are present in
      relatively normal ratios. A/WySnJ x btk(-/-) mice display a B cell-autonomous
      defect, resulting in a developmental block at an earlier stage (T1) than either
      mutation alone, leading to the loss of mature splenic follicular and marginal
      zone B cells, as well as the loss of peritoneal B1 and B2 cell populations. The
      competence of the double mutant T1 B cells to respond to TLR4 and CD40 survival
      and activation signals is further attenuated compared with single mutations as
      evidenced by severely reduced humoral immune responses in vivo and proliferation
      in response to anti-IgM, LPS, and anti-CD40 stimulation in vitro. Thus, BCR and
      BR3 independently and in concert regulate the survival, differentiation, and
      function of all B cell populations at and beyond T1, earliest transitional stage.

PMID- 19843949
TI  - Cyclooxygenase-1 orchestrates germinal center formation and antibody class-switch
      via regulation of IL-17.
AB  - The cyclooxygenase (COX) enzymes are known modulators of innate immune cell
      function; however, their contributions to adaptive immunity are relatively
      unknown. We investigated the roles of COX-1 and COX-2 in the humoral immune
      response to infection with the Lyme disease pathogen Borrelia burgdorferi. We
      report that in vitro, murine B cells constitutively expressed COX-1 and up
      regulated expression of both COX-1 and COX-2 as well as their products PGE(2),
      PGF(2alpha), and thromboxane B(2) and their receptors following stimulation with
      B. burgdorferi or anti-CD40. In vitro inhibition of COX-1 and/or COX-2 in murine
      B cells resulted in decreased eicosanoid production and altered Ab production.
      Importantly, infection of mice lacking COX-1, but not COX-2, activity resulted in
      a defect in Ig class-switching and a lack of Borrelia-specific IgG production.
      This defect correlated with decreased germinal center formation and IL-6 and IL
      17 production, and it could be partially recovered by restoration of IL-6, but
      fully recovered by IL-17. Furthermore, sera from COX-1 inhibitor-treated mice
      were dramatically less effective in killing B. burgdorferi, but borreliacidal
      activity was restored in COX-1 inhibitor-treated mice administered IL-17. We
      conclude that IL-17 plays a role in Ab production and Ig class-switching in
      response to infection and that COX-1 is a critical, previously unrecognized
      regulator of this response.

PMID- 19843950
TI  - Phosphoinositide 3-kinase p110 delta regulates natural antibody production,
      marginal zone and B-1 B cell function, and autoantibody responses.
AB  - B-1 and marginal zone (MZ) B cells produce natural Abs, make Ab responses to
      microbial pathogens, and contribute to autoimmunity. Although the delta isoform
      of the PI3K p110 catalytic subunit is essential for development of these innate
      like B cells, its role in the localization, activation, and function of normal B
      1 and MZ B cells is not known. Using IC87114, a highly selective inhibitor of
      p110delta enzymatic activity, we show that p110delta is important for murine B-1
      and MZ B cells to respond to BCR clustering, the TLR ligands LPS and CpG DNA, and
      the chemoattractants CXCL13 and sphingosine 1-phosphate. In these innate-like B
      cells, p110delta activity mediates BCR-, TLR- and chemoattractant-induced
      activation of the Akt prosurvival kinase, chemoattractant-induced migration, and
      TLR-induced proliferation. Moreover, we found that TLR-stimulated Ab responses by
      B-1 and MZ B cells, as well as the localization of MZ B cells in the spleen,
      depend on p110delta activity. Finally, we show that the in vivo production of
      natural Abs requires p110delta and that p110delta inhibitors can reduce in vivo
      autoantibody responses. Thus, targeting p110delta may be a novel approach for
      regulating innate-like B cells and for treating Ab-mediated autoimmune diseases.

PMID- 19843952
TI  - The roles of the toxicologic pathologist in cancer research.
AB  - Cancer in an important disease throughout the world and a major cause of death in
      both humans and animals. Pathologists play a critical role in cancer research and
      in the diagnosis, treatment, and prevention of human and animal cancers. They
      participate in basic and translational research in laboratories of colleges and
      universities, other research institutes, government research and regulatory
      agencies, and in the biotech, chemical, and pharmaceutical industries. This
      introductory review to the 2009 STP Symposium on Cancer will identify and discuss
      the major roles of pathologists in cancer research.

PMID- 19843951
TI  - T-lineage cells require the thymus but not VDJ recombination to produce IL-17A
      and regulate granulopoiesis in vivo.
AB  - IL-17A and IL-17F regulate granulopoiesis and are produced by memory T cells.
      Rag1(-/-) recombinase-activating gene-deficient mice cannot produce mature T
      cells but maintain normal neutrophil counts. Athymic nude mice are neutropenic or
      have near-normal neutrophil counts, depending on the prevailing intestinal flora,
      and do not produce IL-17A. By contrast, thymi from Rag1(-/-) mice contain as much
      IL-17A as those from wild-type (WT) mice. IL-17A-producing cells are found in the
      double negative DN1 compartment of the Rag1(-/-) thymus and express intracellular
      CD3. These cells colonize the spleen and mesenteric lymph node and secrete IL-17A
      in vitro following stimulation with IL-23 at a level similar to that of WT
      splenocytes. Adoptively transferred Rag1(-/-) or WT thymocytes correct neutrophil
      counts in neutropenic nude mice. We conclude that the development of IL-17A
      producing T-lineage cells requires an intact thymic epithelium, but not V(D)J
      recombination.

PMID- 19843953
TI  - Reproductive lesions in female Harlan Sprague-Dawley rats following two-year oral
      treatment with dioxin and dioxin-like compounds.
AB  - Results from previously published animal studies suggest that prenatal and
      postnatal exposure to dioxin and dioxin-like compounds (DLCs) may profoundly
      affect the reproductive system of both sexes via endocrine disruption. In the
      present work, we evaluate the toxicity and carcinogenicity of various DLCs, with
      an emphasis on their effect on the reproductive organs, induced by chronic
      exposure of female adult Harlan Sprague-Dawley rats. This investigation
      represents part of an initiative of the National Toxicology Program to determine
      the relative potency of chronic toxicity and carcinogenicity of polychlorinated
      dioxins, furans, and biphenyls. For fourteen, thirty-one, or fifty-three weeks or
      for two years, animals were administered by gavage 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8
      pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153);
      2,3',4,4',5-pentachlorobiphenyl (PCB118); a tertiary mixture of TCDD, PCB126, and
      PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and
      PCB118. The ranges of treatment-related changes in the reproductive system
      included chronic active inflammation in the ovary that occurred in the 1,000 and
      3,000 microg/kg core groups (two-year exposure) of PCB153 and in the 300 ng/3,000
      microg/kg core group of binary mixture of PCB126 and PCB153. Increases in the
      incidence of acute and/or chronic active inflammation of the uterus were observed
      in all dosed groups, including the stop-exposure group (withdrawal after thirty
      week exposure) of PeCDF and the 1,000 microg/kg and/or higher group dosed with
      PCB153. The incidence of cystic endometrial hyperplasia was marginally increased
      in the 92 PeCDF ng/kg group at two years. The incidence of squamous metaplasia
      was significantly increased in the 44 ng/kg and higher dose group, including the
      stop-exposure group. The incidence of uterine squamous cell carcinoma was
      significantly or marginally increased in the 6 ng/kg core and 100 ng/kg stop
      exposure groups of TCDD and in the 300 ng/300 microg/kg core group that received
      the binary mixture of PCB126 and 153. The incidence of uterine carcinoma was
      marginally increased in the 92 ng/kg PeCDF group at two years and clearly
      increased in the 1,000 and 4,600 microg/kg PCB118 core group and the 4,600
      microg/kg stop group. In the studies of PCB 126, the tertiary mixture, and the
      binary mixture of PCB126 and PCB118, no increased incidence of any change
      occurred in the reproductive systems. The range of changes seen with the
      different compounds suggests that more than one mechanism may have been involved
      in promoting the female reproductive pathology.

PMID- 19843954
TI  - Focus issue: addressing complicated questions in neuroscience.
AB  - This week Science and Science Signaling turn the spotlight on neuroscience, with
      Science highlighting how advances in methodology are providing insight into the
      organization and regulation of neural circuits and the behavior of neurons.
      Science Signaling features unexpected connections between signaling processes and
      diseases affecting the brain.

PMID- 19843955
TI  - Emerging miniaturized proteomic technologies to study cell signaling in clinical
      samples.
AB  - Recording the state and dynamics of intracellular signaling networks in clinical
      specimens can help identify and validate biomarkers, but may also prove useful in
      developing and monitoring targeted therapies. Studying cell signaling on a system
      wide level in solid tissue, however, is often not feasible using mass
      spectrometry, because this technique generally requires relatively large sample
      quantities. A number of promising miniaturized proteomic technologies have
      emerged, which circumvent these limitations and offer the ability to monitor
      protein abundances and posttranslational modification states in a multiplexed and
      quantitative fashion. These technologies have the potential to accelerate
      molecular diagnostics and therapeutics, and may ultimately facilitate the broad
      adoption of personalized approaches to patient management and treatment.

PMID- 19843956
TI  - Schizophrenia: the "BLOC" may be in the endosomes.
AB  - Genome-wide association studies have identified multiple genetic polymorphisms
      associated with schizophrenia. These polymorphisms conform to a polygenic disease
      model in which multiple alleles cumulatively increase the risk of developing
      disease. Two genes linked to schizophrenia, DTNBP1 and MUTED, encode proteins
      that belong to the endosome-localized Biogenesis of Lysosome-related Organelles
      Complex-1 (BLOC-1). BLOC-1 plays a key role in endosomal trafficking and as such
      has been found to regulate cell-surface abundance of the D2 dopamine receptor,
      the biogenesis and fusion of synaptic vesicles, and neurite outgrowth. These
      functions are pertinent to both neurodevelopment and synaptic transmission,
      processes tightly regulated by selective cell-surface delivery of membrane
      proteins to and from endosomes. We propose that cellular processes, such as
      endosomal trafficking, act as convergence points in which multiple small effects
      from polygenic genetic polymorphisms accumulate to promote the development of
      schizophrenia.

PMID- 19843958
TI  - Two mechanistically and temporally distinct NF-kappaB activation pathways in IL-1
      signaling.
AB  - The cytokine interleukin-1 (IL-1) mediates immune and inflammatory responses by
      activating the transcription factor nuclear factor kappaB (NF-kappaB). Although
      transforming growth factor-beta-activated kinase 1 (TAK1) and mitogen-activated
      protein kinase (MAPK) kinase kinase 3 (MEKK3) are both crucial for IL-1-dependent
      activation of NF-kappaB, their potential functional and physical interactions
      remain unclear. Here, we showed that TAK1-mediated activation of NF-kappaB
      required the transient formation of a signaling complex that included tumor
      necrosis factor receptor-associated factor 6 (TRAF6), MEKK3, and TAK1. Site
      specific, lysine 63-linked polyubiquitination of TAK1 at lysine 209, likely
      catalyzed by TRAF6 and Ubc13, was required for the formation of this complex.
      After TAK1-mediated activation of NF-kappaB, TRAF6 subsequently activated NF
      kappaB through MEKK3 independently of TAK1, thereby establishing continuous
      activation of NF-kappaB, which was required for the production of sufficient
      cytokines. Therefore, we propose that the cooperative activation of NF-kappaB by
      two mechanistically and temporally distinct MEKK3-dependent pathways that diverge
      at TRAF6 critically contributes to immune and inflammatory systems.

PMID- 19843957
TI  - A noisy paracrine signal determines the cellular NF-kappaB response to
      lipopolysaccharide.
AB  - Nearly identical cells can exhibit substantially different responses to the same
      stimulus. We monitored the nuclear localization dynamics of nuclear factor kappaB
      (NF-kappaB) in single cells stimulated with tumor necrosis factor-alpha (TNF
      alpha) and lipopolysaccharide (LPS). Cells stimulated with TNF-alpha have
      quantitative differences in NF-kappaB nuclear localization, whereas LPS
      stimulated cells can be clustered into transient or persistent responders,
      representing two qualitatively different groups based on the NF-kappaB response.
      These distinct behaviors can be linked to a secondary paracrine signal secreted
      at low concentrations, such that not all cells undergo a second round of NF
      kappaB activation. From our single-cell data, we built a computational model that
      captures cell variability, as well as population behaviors. Our findings show
      that mammalian cells can create "noisy" environments to produce diversified
      responses to stimuli.

PMID- 19843959
TI  - STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic
      neuronal cell death.
AB  - Excessive cytosolic calcium ion (Ca(2+)) accumulation during cerebral ischemia
      triggers neuronal cell death, but the underlying mechanisms are poorly
      understood. Capacitive Ca(2+) entry (CCE) is a process whereby depletion of
      intracellular Ca(2+) stores causes the activation of plasma membrane Ca(2+)
      channels. In nonexcitable cells, CCE is controlled by the endoplasmic reticulum
      (ER)-resident Ca(2+) sensor STIM1, whereas the closely related protein STIM2 has
      been proposed to regulate basal cytosolic and ER Ca(2+) concentrations and make
      only a minor contribution to CCE. Here, we show that STIM2, but not STIM1, is
      essential for CCE and ischemia-induced cytosolic Ca(2+) accumulation in neurons.
      Neurons from Stim2(-/-) mice showed significantly increased survival under
      hypoxic conditions compared to neurons from wild-type controls both in culture
      and in acute hippocampal slice preparations. In vivo, Stim2(-/-) mice were
      markedly protected from neurological damage in a model of focal cerebral
      ischemia. These results implicate CCE in ischemic neuronal cell death and
      establish STIM2 as a critical mediator of this process.

PMID- 19843960
TI  - G protein-coupled receptors, cholinergic dysfunction, and Abeta toxicity in
      Alzheimer's disease.
AB  - The beta-amyloid (Abeta) peptide is associated with the pathogenesis of
      Alzheimer's disease (AD). Evidence gathered over the last two decades suggests
      that the gradual accumulation of soluble and insoluble Abeta peptide species
      triggers a cascade of events that leads to the clinical manifestation of AD.
      Abeta accumulation has also been associated with the cholinergic dysfunction
      observed in AD, which is characterized by diminished acetylcholine release and
      impaired coupling of the muscarinic acetylcholine receptors (mAChRs) to
      heterotrimeric GTP-binding proteins (G proteins). Although the mechanism of Abeta
      mediated toxicity is not clearly understood, evidence shows that Abeta
      accumulation has an effect on the oligomerization of the angiotensin II (AngII)
      AT(2) (angiotensin type 2) receptor and sequestration of the Galpha(q/11) family
      of G proteins. Sequestration of Galpha(q/11) results in dysfunctional coupling
      and signaling between M(1) mAChR and Galpha(q/11) and accompanies
      neurodegeneration, tau phosphorylation, and neuronal loss in an AD transgenic
      mouse model. Collectively, these results provide a putative link among Abeta
      toxicity, AT(2) receptor oligomerization, and disruption of the signaling pathway
      through M(1) mAChR and Galpha(q/11) and potentially contribute to our
      understanding of the cholinergic deficit observed in AD.

PMID- 19843962
TI  - Mixing qualitative methods.

PMID- 19843961
TI  - Comparison of 5 health-related quality-of-life indexes using item response theory
      analysis.
AB  - BACKGROUND: Five health-related quality-of-life (HRQoL) indexes--EQ-5D, HUI2,
      HUI3, QWB-SA, and SF-6D--are each used to assign community-based utility scores
      to health states, although these scores differ. OBJECTIVE: The authors transform
      these indexes to a common scale to understand their interrelationships. METHODS:
      Data were from the National Health Measurement Study, a telephone survey of 3844
      US adults. The 5 indexes were analyzed using item response theory analysis to
      estimate scores on an underlying construct of summary health, theta.
      Unidimensionality was evaluated using nonlinear principal components analysis.
      Index scores were plotted against the estimated scores on the common underlying
      construct. In addition, scores on the Health and Activities Limitation Index
      (HALex), the Centers for Disease Control and Prevention Healthy Days questions,
      and self-rated health on a 5-category scale ranging from excellent to poor were
      plotted. RESULTS: SF-6D and QWB-SA are nearly linear across the range of but with
      a shallow slope; EQ-5D, HUI2, and HUI3 are linear with a steep slope from low
      (poor health) into midrange of , then approximately linear with a less steep
      slope for higher (health just below to well above average), although the
      inflection points differ by index. CONCLUSION: Simple linear functions may serve
      as crosswalks among these indexes only for lower health states, albeit with low
      precision. Ceiling effects make crosswalks among most of the indexes ill
      specified above a certain level of health. Although each index measures generic
      health on a utility scale, these indexes are not identical but are relatively
      simply, if imprecisely, related.

PMID- 19843963
TI  - Being there for another with a serious mental illness.
AB  - In this article I describe the unique caring and caretaking relationship between
      a mentally ill person and the nonprofessional caretaker in his or her life.
      Stressing the perspective of the caretaker, I call this relationship "being
      there" for the mentally ill person. I collected the data through in-depth
      interviews and used a descriptive phenomenological approach to unveil the general
      structure of the experience. Eight constituents emerged as central to the general
      structure of this experience: (a) accepting the changed other and grieving the
      loss of who the other once was; (b) taking action in challenging circumstances;
      (c) recognizing the ongoing, never-ending, and sometimes unpredictable nature of
      the experience; (d) feeling isolated; (e) having ambiguity of the heart; (f)
      experiencing the tension of waiting; (g) knowing the other well; and (h) caring
      for the other. Knowledge gained from the study findings will help health care
      professionals understand and support people who are in this experience from a
      more caring paradigm.

PMID- 19843964
TI  - Incomprehensibility in the narratives of individuals with a diagnosis of
      schizophrenia.
AB  - The fact that individuals with a diagnosis of schizophrenia have difficulties in
      terms of ordering and communicating their life stories is well known, and
      undoubtedly these dysfunctions are linked to the experience of alienation and
      isolation. In this article we contribute to the debate by studying life
      narratives of ten patients with a diagnosis of paranoid schizophrenia living in
      care homes in Andalusia, Spain. Patients were selected through meetings held with
      the directors of the care homes and data obtained from narrative, semistructured
      interviews. Thematic self-positioning and structure analysis identified four
      types of clearly distinctive narratives: delusive episodes with invasive voices,
      delusive episodes with no invasive voices, absence of delusive episodes or
      invasive voices and domination of self-position as patient, and complexity and
      articulation of self-positions.

PMID- 19843965
TI  - Women's accounts of their decision to quit taking antidepressants.
AB  - Over the past 15 years, the rates at which antidepressants are prescribed have
      increased dramatically. Adherence, however, is often low and considered to be
      problematic. Using a discursive approach to analyzing interviews with six
      Canadian women who chose unilaterally to discontinue their use of
      antidepressants, we focus on three rhetorical strategies used to justify their
      actions: (a) referencing the actual or potential effects of antidepressants, (b)
      positioning lay knowledge as superior to expert medical knowledge, and (c)
      denigrating medical authorities. We argue that these women drew on the
      responsible-use-of-drugs framework as a way of positioning themselves against
      potential charges of having engaged in an irrational act.

PMID- 19843966
TI  - Experiencing "the other side": a study of empathy and empowerment in general
      practitioners who have been patients.
AB  - Work-related pressures and susceptibility to health problems mean that many
      general practitioners (GPs) will, at some stage, experience the role of patient.
      However qualitative evidence about their experiences of illness and patienthood
      is sparse. Our study offers an interpretative perspective on GPs' experiences of
      illness and the influence that this has had on their practice. Seventeen GPs who
      had experienced significant illness took part in semistructured interviews. Data
      were analyzed using interpretative phenomenological analysis (IPA). The findings
      highlight the relationship between empathy and empowerment and explore the role
      of self-disclosure of GP status by GPs in consultations. We make suggestions as
      to how empathy in doctor-patient relationships can be developed through
      consideration of power and status as well as through interaction with patients
      from similar backgrounds. Future research should focus on more specific ways to
      integrate these ideas into medical training.

PMID- 19843968
TI  - Ethical dilemmas: the experiences of israeli nurses.
AB  - In this study I explored ethical dilemmas in nursing to gain a better
      understanding of nurses' work and their professional status. Qualitative data on
      ethical dilemmas were collected by interviewing 52 nurses in 18 hospitals and
      health maintenance organizations. The transcribed interviews were analyzed using
      a stepwise method. Results indicate a large number of dilemmas that can be
      divided into five main categories: caring vs. following formal codes; fair
      process vs. fair outcome; organizational standards vs. family agenda; autonomy
      vs. deference to higher authority, and guarding secrecy vs. duty to report. The
      study findings might enhance nurses' ability to cope with ethical dilemmas and
      bring about change in their professional status. In addition, the results might
      guide nurses and their supervisors toward developing practitioner programs for
      nurses that deal with ethical aspects. All these might reduce the expected
      shortage of nurses and improve the ability of the system to provide quality
      health care.

PMID- 19843967
TI  - African American Women's beliefs, coping behaviors, and barriers to seeking
      mental health services.
AB  - Little is known about African American women's beliefs about mental illness. In
      this qualitative study we employed the Common Sense Model (CSM) to examine
      African American women's beliefs about mental illness, coping behaviors, barriers
      to treatment seeking, and variations in beliefs, coping, and barriers associated
      with aging. Fifteen community-dwelling African American women participated in
      individual interviews. Dimensional analysis, guided by the CSM, showed that
      participants believed general, culturally specific, and age-related factors can
      cause mental illness. They believed mental illness is chronic, with negative
      health outcomes. Participants endorsed the use of prayer and counseling as coping
      strategies, but were ambivalent about the use of medications. Treatment-seeking
      barriers included poor access to care, stigma, and lack of awareness of mental
      illness. Few age differences were found in beliefs, coping behaviors, and
      barriers. Practice and research implications are discussed.

PMID- 19843969
TI  - Recovery from total hip replacement surgery: "it's not just physical".
AB  - In this grounded theory study we explored the process of recovery following total
      hip replacement (THR) surgery from the perspective of the older adult. In-depth
      interviews were conducted with 10 patients aged more than 65 years who had been
      discharged from hospital for a period of 4 to 6 months following THR surgery.
      Findings showed that three distinct but interrelated processes constitute the
      physical, psychological, and social recovery process: reclaiming physical
      ability, reestablishing roles and relationships, and refocusing self. Intervening
      conditions affecting the recovery process include comorbid conditions, the
      personal outlook of the patient, patients' relationships, and social support. The
      recovery process can lead to changes in personal and social functioning that
      patients might not anticipate. Awareness of potential changes will inform patient
      education and enable clinicians to develop strategies that facilitate THR
      patients' return to health.

PMID- 19843970
TI  - Positions in doctors' questions during psychiatric interviews.
AB  - In this article I apply the concept of positioning to the analysis of 15 initial
      psychiatric interviews. I argue that through their questions the psychiatrists-in
      training impose positions requiring the patients to gaze at themselves and their
      actual problems from particular perspectives. I point to three such positions:
      (a) the position of the observing assessor, from which it is expected that the
      patients will make a detached assessment of themselves or their problems, (b) the
      position of the informing witness, which requires the patients only to verify the
      information about themselves, and (c) the marginal one, the position of the
      experiencing narrator, from which talk about experiences and problems is
      expected. I explore the roots and consequences of the positions, with particular
      attention toward objectivization of the patients' experiences in the dominant
      witness and assessor positions. I conclude with a discussion about the medical
      model in psychiatry.

PMID- 19843971
TI  - Protecting respondent confidentiality in qualitative research.
AB  - For qualitative researchers, maintaining respondent confidentiality while
      presenting rich, detailed accounts of social life presents unique challenges.
      These challenges are not adequately addressed in the literature on research
      ethics and research methods. Using an example from a study of breast cancer
      survivors, I argue that by carefully considering the audience for one's research
      and by reenvisioning the informed consent process, qualitative researchers can
      avoid confidentiality dilemmas that might otherwise lead them not to report rich,
      detailed data.

PMID- 19843972
TI  - Practicing the awareness of embodiment in qualitative health research:
      methodological reflections.
AB  - Although the importance of the researcher's embodiment has been noted in health
      and social sciences research, in many instances, more attention has been paid to
      the embodiment of the researched. Thus, more in-depth analysis of the embodied
      researcher can illuminate qualitative inquiry. The influence of the embodied
      researcher became visible in a recent critical ethnographic study examining the
      negotiation of religious, spiritual, and cultural plurality in health care. In
      this article, we do not present research findings per se, but rather
      methodological reflections. As researchers, we highlight emotional and bodily
      ways of knowing and experiences of difference such as culture, race, and religion
      as embodied and a part of researcher-participant encounters. We aim to elucidate
      the awareness of being embodied researchers, and with this elucidation, we
      consider implications for knowledge generation for health and social sciences.

PMID- 19843975
TI  - Influence of cyclooxygenase inhibitors on the function of the prostaglandin
      transporter organic anion-transporting polypeptide 2A1 expressed in human
      gastroduodenal mucosa.
AB  - The human organic anion-transporting polypeptide 2A1 (OATP2A1) is a prostaglandin
      transporter expressed in several tissues and plays an important role for local
      distribution of prostaglandins, which contribute to the integrity of gastric
      mucosa. Blockade of prostaglandin pathways by cyclooxygenase (COX) inhibitors has
      been associated with serious side effects such as gastrointestinal ulceration and
      bleeding. However, little is known regarding OATP2A1 expression in the upper
      gastrointestinal tract and the potential impact of cyclooxygenase inhibitors on
      OATP2A1 function. We first investigated the expression of OATP2A1 mRNA and
      protein in human gastroduodenal mucosa using human biopsy specimens obtained from
      antrum, corpus, and duodenum. The results indicate that OATP2A1 is expressed in
      the neck region and deep pyloric glands of antrum and in parietal cells of
      gastric corpus. Second, we examined various COX inhibitors for their effects on
      OATP2A1 transporter activity. Using HEK293 cells expressing OATP2A1, we found
      that diclofenac and lumiracoxib are potent inhibitors of OATP2A1-mediated
      transport of prostaglandin (PG) E(2) with IC(50) values of 6.2 +/- 1.2 and 3.1 +/
      1.2 microM. In contrast, indomethacin, ketoprofen, and naproxen led to
      significant stimulation of OATP2A1-mediated PGE(2) transport by 162.7 +/- 13.9,
      77.2 +/- 3.6, and 32.3 +/- 4.9%, respectively. Taken together, our results
      suggest that various clinically used COX inhibitors have differential impact on
      the function of the prostaglandin transporter OATP2A1 in human stomach and that
      these effects may contribute to differences in the gastrointestinal side effects
      of COX inhibitors.

PMID- 19843974
TI  - Corticotropin-releasing factor (CRF) sensitization of ethanol withdrawal-induced
      anxiety-like behavior is brain site specific and mediated by CRF-1 receptors:
      relation to stress-induced sensitization.
AB  - In abstinent alcoholics, stress induces negative affect-a response linked to
      craving and relapse. In rats, repeated stresses at weekly intervals before 5-day
      ethanol diet sensitize withdrawal-induced anxiety-like behavior ("anxiety") that
      is blocked by a corticotrophin-releasing factor 1 (CRF-1)-receptor antagonist.
      Current experiments were performed to identify brain sites that support CRF
      involvement in stress sensitization of ethanol withdrawal-induced anxiety-like
      behavior. First, different doses of CRF microinjected weekly into the central
      amygdala (CeA) before ethanol exposure produced a dose-related sensitization of
      anxiety during ethanol withdrawal. Subsequently, CRF microinjection into the
      basolateral amygdala, dorsal raphe nucleus (DRN), or dorsal bed nucleus of the
      stria terminalis (d-BNST) also sensitized ethanol withdrawal-induced anxiety. In
      contrast, sensitization of ethanol withdrawal-induced anxiety was not observed
      after weekly CRF administration into the ventral-BNST, CA1-hippocampal region, or
      hypothalamic-paraventricular nucleus. Then, experiments documented the CRF
      receptor subtype responsible for CRF and stress sensitization of withdrawal
      induced anxiety. Systemic administration of a CRF-1 receptor antagonist before
      CRF microinjection into the CeA, DRN, or d-BNST prevented CRF-induced
      sensitization of anxiety during ethanol withdrawal. Furthermore, repeated
      microinjections of urocortin-3, a CRF-2 receptor agonist, into the CRF-positive
      sites did not sensitize anxiety after withdrawal from ethanol. Finally,
      microinjection of a CRF-1 receptor antagonist into the CeA, DRN, or d-BNST before
      stress blocked sensitization of anxiety-like behavior induced by the repeated
      stress/ethanol withdrawal protocol. These results indicate that CRF released by
      stress acts on CRF-1 receptors within specific brain regions to produce a
      cumulative adaptation that sensitizes anxiety-like behavior during withdrawal
      from chronic ethanol exposure.

PMID- 19843976
TI  - Brain-derived neurotrophic factor signaling modulates cocaine induction of reward
      associated ultrasonic vocalization in rats.
AB  - Cocaine exhibits high liability for inducing addictive behaviors, but the
      mechanisms of neuroplasticity underlying the behavioral effects remain unclear.
      As a crucial mediator of neuroplasticity in diverse functional models, brain
      derived neurotrophic factor (BDNF) could contribute to the mechanisms of
      addiction-related neuroplasticity. Here, we addressed the hypothesis that cocaine
      increases synaptic dopamine, which induces BDNF protein expression to initiate
      addiction-related behavior in the rat. An enzyme-linked immunosorbent assay was
      used to measure BDNF protein expression in rat striatal tissues. For behavioral
      readout, we used a noninvasive measurement system to measure the emission of 50
      kHz ultrasonic vocalization (USV), a response that correlates with electrical
      brain stimulation and conditioned place preference behavior in rodents. A single
      injection of cocaine significantly increased BDNF protein expression, but this
      effect was not further augmented by repeated cocaine administration. A single
      administration of cocaine elicited significant and dose-related USV responses,
      and the magnitude of the behavior increased with repeated drug administration. R
      (+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      (SCH23390), but not raclopride, significantly attenuated cocaine-induced BDNF
      protein expression, whereas either the D(1)-like or D(2)-like receptor antagonist
      blocked cocaine-induced USV behavior. Furthermore, significant USV behavior was
      elicited by the nonselective dopamine agonist, apomorphine, but not by agonists
      that are selective for D(1)-like or D(2)-like receptors. Intracerebroventricular
      injection of the neurotrophin TrkB receptor inhibitor, K252a, blocked cocaine
      induced USV behavior but not locomotor activity. These results suggest that
      neurotrophin signaling downstream of dopamine receptor function probably
      constitutes a crucial link in cocaine induction of USV behavior and may
      contribute to the mechanisms underlying the development of addiction-related
      behaviors.

PMID- 19843978
TI  - Elvitegravir: a new HIV integrase inhibitor.
AB  - Integration is a distinctive and essential process in the HIV infection cycle and
      thus represents an attractive antiviral drug target. Integrase inhibitors
      combined with other classes of drug might contribute to long-lasting suppression
      of HIV type-1 (HIV-1) replication for many patients. Of the numerous potential
      integrase inhibitor leads that have been reported, few have reached clinical
      trials and only one, raltegravir, has been approved (in late 2007) for the
      treatment of HIV-1-infected patients. Another integrase inhibitor, elvitegravir,
      is currently showing promise in Phase III clinical studies. Once-daily
      administration of elvitegravir has a comparable antiviral activity to twice-daily
      of raltegravir in HIV-1-infected patients. Here, we highlight the salient
      features of elvitegravir: its chemical structure compared with representative
      integrase inhibitors, mechanism of action, in vitro and in vivo activity against
      HIV and other retroviruses, and the effect of integrase polymorphisms and
      resistance mutations on its anti-HIV activity.

PMID- 19843979
TI  - Inhibition of herpes simplex virus by polyamines.
AB  - BACKGROUND: Herpes simplex virus (HSV) establishes latent infection in humans
      with periodic reactivation. Acyclovir, valacyclovir and foscarnet are in medical
      use today against HSV type-1 (HSV-1) and type-2 (HSV-2), inhibiting the DNA
      synthesis of the viruses. Additional drugs that will affect the growth of these
      viruses by other mechanisms and also decrease the frequency of appearance of drug
      resistant mutants are required. METHODS: Cationic polysaccharides were
      synthesized by conjugation of various oligoamines to oxidized polysaccharides by
      reductive amination. Polycations of dextran, pullulan and arabinogalactan were
      grafted with oligoamines of 2-4 amino groups forming Schiff-base imine-based
      conjugates followed by reduction with borohydride to obtain the stable amine
      based conjugate. Evaluation of toxicity to BS-C-1 cells and antiviral activity
      against HSV-1 and HSV-2 of the different compounds was performed in vitro by a
      semiquantitative assay. A quantitative study with a selected compound followed.
      RESULTS: Structure-activity relationship studies showed that the nature of the
      grafted oligoamine of the polycation plays an essential role in the antiviral
      activity against HSV-1 and HSV-2. Dextran-propan-1,3-diamine (DPD) was found to
      be the most potent of all the compounds examined. DPD did not decrease the
      infectivity of HSV upon direct exposure to the virions. The growth of HSV was
      significantly inhibited when DPD was added to the host cells 1 h prior to
      infection, thus preventing the adsorption and penetration of the virus into the
      cells. CONCLUSIONS: Our in vitro data warrant clinical investigation. DPD could
      have an advantage as a topical application in combination therapy of HSV lesions.

PMID- 19843977
TI  - Antiretroviral therapy in macrophages: implication for HIV eradication.
AB  - HIV type-1 (HIV-1) accounts for more than 25 million deaths and nearly 40 million
      people are infected worldwide. A significant obstacle in clearing virus from
      infected individuals is latently infected viral reservoirs. Latent HIV-1 can
      emerge with recrudescence as a productive infection later in disease progression
      and could provide a source for the emergence of resistant HIV-1. It is widely
      recognized that macrophages represent a latently infected viral reservoir and are
      a significant and critical HIV-1 target cell in vivo. Macrophages can be divided
      into multiple subsets of macrophage-like cells, all of which are susceptible to
      HIV-1 infection, including dendritic cells, Langerhans cells, alveolar
      macrophages, mucosal macrophages and microglial cells. Current antiretroviral
      therapy (ART) often displays differential antiviral activity in macrophages
      relative to CD4(+) T-lymphocytes. Significant work has been performed to
      establish antiviral activity of many clinically approved ART in macrophages;
      however, a direct link between antiviral activity and specific mechanisms
      responsible for these antiviral effects are incompletely understood. This review
      identifies many understudied areas of research, along with topics for further
      research in the field of HIV therapy and eradication. Discussion focuses upon the
      known cellular pharmacology and antiviral activity of antiretroviral agents in
      macrophages and its relationship to latency, chronic HIV-1 infection and
      therapeutic strategies to eradicate systemic HIV-1 infection.

PMID- 19843980
TI  - Anti-hepatitis C virus activity of novel beta-d-2'-C-methyl-4'-azido pyrimidine
      nucleoside phosphoramidate prodrugs.
AB  - BACKGROUND: 2'-C-methyl and 4'-azido nucleosides have previously demonstrated
      inhibition of hepatitis C virus (HCV) replication by targeting the RNA-dependent
      RNA polymerase NS5B. In an effort to discover new and more potent anti-HCV
      agents, we envisioned synthesizing nucleoside analogues by combining the 2'-C
      methyl-moiety with the 4'-azido-moiety into one molecule. METHODS: 2'-C-methyl-4'
      azido pyrimidine nucleosides were synthesized by first converting 2'-C-methyl
      ribonucleosides to the corresponding 4'-exocyclic methylene nucleosides.
      Treatment with iodine azide, benzoylation of the 2'- and 3'-hydroxy groups,
      oxidative displacement of the 5'-iodo group with meta-chloroperoxybenzoic acid,
      and debenzoylation gave the desired 2'-C-methyl-4'-azido uridine and thymidine
      analogues in good yield. Standard conversion of uridine to cytidine via the 4
      triazole yielded 2'-C-methyl-4'-azido cytidine. In addition, 5'-phosphoramidate
      derivatives of 2'-C-methyl-4'-azido uridine and cytidine were synthesized to
      bypass the initial phosphorylation step. RESULTS: The prepared nucleosides and
      their 5'-monophosphate prodrugs were evaluated for their ability to inhibit
      replication of the hepatitis C virus in a subgenomic replicon cell based assay.
      Cytotoxicity in Huh7 cells was determined simultaneously with anti-HCV activity
      by extraction and amplification of both HCV RNA and ribosomal RNA. Among the
      newly synthesized compounds, only the 5'-monophosphate nucleoside prodrugs had
      modest and selective anti-HCV activity. All prepared pyrimidine nucleosides and
      5'-monophosphate nucleoside prodrugs displayed no evidence of cytotoxicity at
      high concentrations. CONCLUSIONS: This work is the first example of both inactive
      uridine and cytidine analogues of a nucleoside being converted to active anti-HCV
      nucleosides via 5'-monophosphate prodrugs.

PMID- 19843981
TI  - Automatic detection and classification of human epicardial atrial unipolar
      electrograms.
AB  - This paper describes an unsupervised signal processing method applied to three
      channel unipolar electrograms recorded from human atria. These were obtained by
      epicardial wires sutured on the right and left atria after coronary artery bypass
      surgery. Atrial (A) and ventricular (V) activations had to be detected and
      identified on each channel, and gathered across the channels when belonging to
      the same global event. The algorithm was developed and optimized on a training
      set of 19 recordings of 5 min. It was assessed on twenty-seven 2 h recordings
      taken just before the onset of a prolonged atrial fibrillation for a total of
      1593697 activations that were validated and classified as normal atrial or
      ventricular activations (A, V) and premature atrial or ventricular activations
      (PAA, PVA). 99.93% of the activations were detected, and amongst these, 99.89% of
      the A and 99.75% of the V activations were correctly labelled. In the subset of
      the 39705 PAA, 99.83% were detected and 99.3% were correctly classified as A. The
      false positive rate was 0.37%. In conclusion, a reliable fully automatic
      detection and classification algorithm was developed that can detect and
      discriminate A and V activations from atrial recordings. It can provide the time
      series needed to develop a monitoring system aiming to identify dynamic
      predictors of forthcoming cardiac events such as postoperative atrial
      fibrillation.

PMID- 19843982
TI  - Modeling the frequency dependence of the electrical properties of the live human
      skull.
AB  - An accurate impedance model of a skull plays an important role in the simulation
      research on source localization of EEG and brain EIT (electrical impedance
      tomography), etc. On the basis of the large number of impedance and resistivity
      data obtained from our previous measurement on the live human skull, in this
      study we established the equivalent circuit models of six types of skull samples
      in the 30 Hz-3 MHz frequency range and analyzed the fitting performance of the
      models. The six types of skull samples are standard tri-layer, quasi-tri-layer,
      standard compact, quasi-compact, dentate suture and squamous suture. The results
      showed that the difference of the real part between the CPE (constant phase
      model) model and the measured data was less than 1% for all skull tissue types
      when the optimized characteristic parameters (rho(0), rho(infinity), alpha and
      f(c)) were adopted in the model. It is the first time studying the impedance
      model of different types of skulls, and it may provide accurate modeling of the
      skull to improve the accuracy of the related research on bioelectricity of the
      head and the biological effects of the electromagnetic field.

PMID- 19843983
TI  - The cellular response to curvature-induced stress.
AB  - We present a theoretical model to explain recent observations of the
      orientational response of cells to unidirectional curvature. Experiments show
      that some cell types when plated on a rigid cylindrical surface tend to reorient
      their shape and stress fibers along the axis of the cylinder, while others align
      their stress fibers perpendicular to that axis. Our model focuses on the
      competition of the shear stress--that results from cell adhesion and active
      contractility--and the anisotropic bending stiffness of the stress fibers. We
      predict the cell orientation angle that results from the balance of these two
      forces in a mechanical equilibrium. The conditions under which the different
      experimental observations can be obtained are discussed in terms of the theory.

PMID- 19843984
TI  - Physical limits of feedback noise-suppression in biological networks.
AB  - Feedback is a ubiquitous control mechanism of biological networks, and has also
      been identified in a variety of regulatory systems and organisms. It has been
      shown that, for a given gain and with negligible intrinsic noise, negative
      feedback impairs noise buffering whereas positive feedback enhances noise
      buffering. We further investigate the influence of negative and positive feedback
      on noise in output signals by considering both intrinsic and extrinsic noise as
      well as operator noise. We find that, while maintaining the system sensitivity,
      either there exists a minimum of the output noise intensity corresponding to a
      biologically feasible feedback strength, or the output noise intensity is a
      monotonic function of feedback strength bounded by both biological and dynamical
      constraints. In both cases, feedback noise-suppression is physically limited. In
      other words, noise suppressed by negative or positive feedback cannot be reduced
      without limitation even in the case of slow transcription.

PMID- 19843985
TI  - A model for signal transduction during quorum sensing in Vibrio harveyi.
AB  - We present a framework for analyzing luminescence regulation during quorum
      sensing in the bioluminescent bacterium Vibrio harveyi. Using a simplified model
      for signal transduction in the quorum sensing pathway, we identify key
      dimensionless parameters that control the system's response. These parameters are
      estimated using experimental data on luminescence phenotypes for different mutant
      strains. The corresponding model predictions are consistent with results from
      other experiments which did not serve as input for determining model parameters.
      Furthermore, the proposed framework leads to novel testable predictions for
      luminescence phenotypes and for responses of the network to different
      perturbations.

PMID- 19843986
TI  - Functionalizing titania nanoparticle surfaces in a fluidized bed plasma reactor.
AB  - Functionalizing nanoparticle surfaces is essential for achieving homogeneous
      dispersions of monodisperse particles in polymer nanocomposites for successful
      utilization in engineering applications. Functionalization reduces the surface
      energy of the nanoparticles, thereby limiting the tendency to agglomerate.
      Moreover, reactive groups on the surface can also participate in the
      polymerization, creating covalent bonds between the inorganic and organic phases.
      In this paper, a fluidized bed inductively coupled plasma (FB-ICP) reactor is
      used to break apart the agglomerates and functionalize commercial TiO2
      nanoparticle powders in a batch of several grams. The fluidized bed could be
      implemented into a continuous flow reactor, potentially making this a viable
      method to treat larger quantities of commercial powders. The particles are
      treated with acrylic acid (AA) and tetraethylorthosilicate (TEOS) plasma and the
      functionalized particles were collected separately from bulk powder. High
      resolution transmission electron microscopy (HRTEM) analysis showed that the
      particles were coated uniformly with polymer coatings with thicknesses around a
      few nanometers. Fourier-transformed infrared spectroscopy (FTIR) studies of the
      polymer-coated particles showed the presence of different functional groups (poly
      acrylic acid/siloxane) similar to that present in the bulk films. The dispersion
      behavior of the TiO2 nanoparticles showed much improvement with reduced
      agglomerate size.

PMID- 19843987
TI  - Oxide mediated liquid-solid growth of high aspect ratio aligned gold silicide
      nanowires on Si(110) substrates.
AB  - Silicon nanowires grown using the vapor-liquid-solid method are promising
      candidates for nanoelectronics applications. The nanowires grow from an Au-Si
      catalyst during silicon chemical vapor deposition. In this paper, the effect of
      temperature, oxide at the interface and substrate orientation on the nucleation
      and growth kinetics during formation of nanogold silicide structures is explained
      using an oxide mediated liquid-solid growth mechanism. Using real time in situ
      high temperature transmission electron microscopy (with 40 ms time resolution),
      we show the formation of high aspect ratio ( approximately 15.0) aligned gold
      silicide nanorods in the presence of native oxide at the interface during in situ
      annealing of gold thin films on Si(110) substrates. Steps observed in the growth
      rate and real time electron diffraction show the existence of liquid Au-Si nano
      alloy structures on the surface besides the un-reacted gold nanostructures. These
      results might enable us to engineer the growth of nanowires and similar
      structures with an Au-Si alloy as a catalyst.

PMID- 19843988
TI  - Batch-fabricated flexible carbon nanotubes' photosensor array.
AB  - This study reports a flexible carbon nanotubes' (fCNTs) photosensor for light
      detection. The fCNTs photosensor is batch-fabricated using micromachining
      processes. In this device, CNTs (carbon nanotubes) are embedded into the flexible
      Parylene-C film using a batch micromachining process. Through this fabrication
      process, CNTs act as the component for light detection, and Parylene-C provides
      the flexibility of the device. In application, the fCNTs photosensor is
      implemented. The photocurrent response measurements indicate that the presented
      fCNTs photosensor operated as a function of heterostructure interface, pressure,
      light intensity and bias voltage under red laser illumination. The quantum
      efficiency of the fabricated fCNTs device is about 0.063% at atmospheric
      pressure, and becomes 1.93% in a vacuum of 3 mTorr. Thus, the presented fCNTs
      device has the potential for photosensor application. The position detection of a
      light source using the fCNTs photosensor array has also been demonstrated.

PMID- 19843989
TI  - The effect of bundling on the G' Raman band of single-walled carbon nanotubes.
AB  - The behaviour of the Raman G' band of solubilized SWCNTs in aqueous solution is
      investigated with respect to ultrasonication time, surfactant type and
      centrifugation. The linewidth of the high frequency component of the G' band is
      shown to correlate with the degree of bundling in the solution. In particular,
      the linewidths of all dispersions decrease as a consequence of subsequent
      centrifugation, reaching values characteristic of individual SWCNTs (30 cm(-1)).
      These results correlate well with the observed changes of the radial breathing
      modes. Further, using this approach an evaluation of the extent of debundling
      SWCNTs using surfactant solutions (sodium dodecylbenzenesulfonate and sodium
      dodecyl sulfate) and deoxyribonucleic acids with respect to surfactant
      concentration, ultrasonication time and centrifugation was performed.

PMID- 19843990
TI  - Evidence of space charge regions within semiconductor nanowires from Kelvin probe
      force microscopy.
AB  - We have studied the equilibrium electrostatic profile of III-V semiconductor
      nanowires using Kelvin probe force microscopy. Qualitative agreement of the
      measured surface potential levels and expected Fermi level variation for pure InP
      and InAs nanowires is obtained from electrical images with spatial resolution as
      low as 10 nm. Surface potential mapping for pure and heterostructured nanowires
      suggests the existence of charge transfer mechanisms and the formation of a metal
      semiconductor electrical contact at the nanowire apex.

PMID- 19843991
TI  - Superconducting transition in Nb nanowires fabricated using focused ion beam.
AB  - Making use of focused Ga-ion beam (FIB) fabrication technology, the evolution
      with device dimension of the low-temperature electrical properties of Nb
      nanowires has been examined in a regime where crossover from Josephson-like to
      insulating behaviour is evident. Resistance-temperature data for devices with a
      physical width of order 100 nm demonstrate suppression of superconductivity,
      leading to dissipative behaviour that is shown to be consistent with the
      activation of phase-slip below T(c). This study suggests that by exploiting the
      Ga-impurity poisoning introduced by the FIB into the periphery of the nanowire, a
      central superconducting phase-slip nanowire with sub-10 nm dimensions may be
      engineered within the core of the nanowire.

PMID- 19843992
TI  - Comment on 'Electron-phonon scattering in Sn-doped In2O3 FET nanowires probed by
      temperature-dependent measurements'.
AB  - We point out that the recently reported electrical quantities and transport
      behavior in a Sn-doped indium oxide FET nanowire (Berengue et al 2009
      Nanotechnology 20 245706) should require serious reevaluation.

PMID- 19843993
TI  - ZnO nanorod array solid phase micro-extraction fiber coating: fabrication and
      extraction capability.
AB  - In this paper, a ZnO nanorod array has been introduced as a coating to the
      headspace solid phase micro-extraction (HSSPME) field. The coating shows good
      extraction capability for volatile organic compounds (VOCs) by use of BTEX as a
      standard and can be considered suitable for sampling trace and small molecular
      VOC targets. In comparison with the randomly oriented ZnO nanorod HSSPME coating,
      ZnO nanorod array HSSPME fiber coating shows better extraction capability, which
      is attributed to the nanorod array structure of the coating. Also, this novel
      nanorod array coating shows good extraction selectivity to 1-propanethiol.

PMID- 19843994
TI  - N-P transition sensing behaviors of ZnO nanotubes exposed to NO2 gas.
AB  - Hydrothermally synthesized ZnO nanotube arrays were used to fabricate the gas
      sensor for detection of the toxic gas NO2. The ZnO nanotube gas sensor exhibited
      sensitive response to NO2 down to 500 ppb at low temperature 30 degrees C.
      Abnormal temperature-dependent and concentration-dependent N-P transition
      behaviors were observed. The excellent sensing ability of the sensor and their
      anomalous conductivity behaviors may be attributed to the unique surface
      conductivity related to the hollow nanostructure feature. These sensing behaviors
      may help to comprehensively understand the sensing mechanism of 1D ZnO
      nanostructures and improve the selectivity of the ZnO gas sensor.

PMID- 19843995
TI  - Graphene to graphane: a theoretical study.
AB  - Graphane is a two-dimensional system consisting of a single layer of fully
      saturated (sp(3) hybridization) carbon atoms. In an ideal graphane structure C-H
      bonds exhibit an alternating pattern (up and down with relation to the plane
      defined by the carbon atoms). In this work we have investigated, using ab initio
      and reactive molecular dynamics simulations, the role of H frustration (breaking
      the H atoms' up and down alternating pattern) in graphane-like structures. Our
      results show that a significant percentage of uncorrelated H frustrated domains
      are formed in the early stages of the hydrogenation process leading to membrane
      shrinkage and extensive membrane corrugations. These results also suggest that
      large domains of perfect graphane-like structures are unlikely to be formed, as H
      frustrated domains are always present.

PMID- 19843997
TI  - Semiconducting III-V nanowires with nanogaps for molecular junctions: DFT
      transport simulations.
AB  - We consider here the possibility of using III-V heterostructure nanowires as
      electrodes for molecular electronics instead of metal point contacts. Using ab
      initio electronic structure and transport calculations, we study the effect on
      electronic properties of placing a small molecule with thiol linking groups,
      benzene-di-thiol (BDT), within a nanosize gap in a III-V nanowire. Furthermore,
      it is investigated how surface states affect the transport through pristine III-V
      nanowires and through the BDT molecule situated within the nanogap. Using GaAs
      and GaP as III-V materials we find that the BDT molecule provides transport
      through the entire system comparable to the case of gold electrodes.

PMID- 19843998
TI  - DNA-templated synthesis of Pt nanoparticles on single-walled carbon nanotubes.
AB  - A series of electron microscopy characterizations demonstrate that single
      stranded deoxyribonucleic acid (ssDNA) can bind to nanotube surfaces and disperse
      bundled single-walled carbon nanotubes (SWCNTs) into individual tubes. The ssDNA
      molecules on the nanotube surfaces demonstrate various morphologies, such as
      aggregated clusters and spiral wrapping around a nanotube with different pitches
      and spaces, indicating that the morphology of the SWCNT/DNA hybrids is not
      related solely to the base sequence of the ssDNA or the chirality or the diameter
      of the nanotubes. In addition to serving as a non-covalent dispersion agent, the
      ssDNA molecules bonded to the nanotube surface can provide addresses for
      localizing Pt(II) complexes along the nanotubes. The Pt nanoparticles obtained by
      a reduction of the Pt2+-DNA adducts are crystals with a size of < or =1-2 nm.
      These results expand our understanding of the interactions between ssDNA and
      SWCNTs and provide an efficient approach for positioning Pt and other metal
      particles, with uniform sizes and without aggregations, along the nanotube
      surfaces for applications in direct ethanol/methanol fuel cells and nanoscale
      electronics.

PMID- 19843999
TI  - Electron beam stimulated oxidation of carbon.
AB  - The patterning of carbon nanostructures by electron beam stimulated oxidation is
      described. Sputter deposited carbon thin films and carbon nanotubes are locally
      oxidized in a scanning electron microscope using injected water vapor. The
      resulting structures are examined with scanning electron microscopy and
      transmission electron microscopy. The electrical resistance obtained
      postprocessing is comparable to the as-deposited values. Linewidths are
      demonstrated down to 20 nm along with sub-2 nm nanowire fabrication in sputtered
      carbon films. A carbon nanowire is fabricated using this process and electrically
      characterized.

PMID- 19844000
TI  - Gate-controlled quantum collimation in nanocolumn resonant tunneling transistors.
AB  - Nanoscaled resonant tunneling transistors (RTT) based on MBE-grown GaAs/AlAs
      double-barrier quantum well (DBQW) structures have been fabricated by a top-down
      approach using electron-beam lithographic definition of the vertical nanocolumns.
      In the preparation process, a reproducible mask alignment accuracy of below 10 nm
      has been achieved and the all-around metal gate at the level of the DBQW
      structure has been positioned at a distance of about 20 nm relative to the
      semiconductor nanocolumn. Due to the specific doping profile n++/i/n++ along the
      transistor nanocolumn, a particular confining potential is established for
      devices with diameters smaller than 70 nm, which causes a collimation effect of
      the propagating electrons. Under these conditions, room temperature optimum
      performance of the nano-RTTs is achieved with peak-to-valley current ratios above
      2 and a peak current swing factor of about 6 for gate voltages between -6 and +6
      V. These values indicate that our nano-RTTs can be successfully used in low power
      fast nanoelectronic circuits.

PMID- 19844001
TI  - Advances and synergy of high-pressure sciences at synchrotron sources.

PMID- 19844002
TI  - Achievements in high-pressure science at the high-brilliance energy-dispersive X
      ray absorption spectrometer of ESRF, ID24.
AB  - Although the idea of an X-ray absorption spectrometer in dispersive geometry was
      initially conceived for the study of transient phenomena, the instrument at the
      European Synchrotron Radiation facility has been increasingly exploited for
      studies at extreme conditions of pressure using diamond anvil cells. The main
      results of investigations at high pressure obtained at beamline ID24 are
      reviewed. These concern not only fundamental topics, such as the local and the
      electronic structure as well as the magnetic properties of matter, but also
      geological relevant questions such as the behaviour of Fe in the main components
      of the Earth's interior.

PMID- 19844003
TI  - Phonon spectroscopy at high pressure by inelastic X-ray scattering.
AB  - The current status of phonon-dispersion studies at high pressure using very high
      energy resolution inelastic X-ray scattering is discussed. A brief description of
      the instrumental apparatus is given, together with an illustration of the high
      pressure facilities available at the IXS beamlines ID16 and ID28 of the ESRF.
      Some selected examples of recent studies on crystalline and liquid samples in a
      diamond anvil cell are then presented.

PMID- 19844004
TI  - Sound velocities of compressed Fe3C from simultaneous synchrotron X-ray
      diffraction and nuclear resonant scattering measurements.
AB  - The applications of nuclear resonant scattering in laser-heated diamond anvil
      cells have provided an important probe for the magnetic and vibrational
      properties of (57)Fe-bearing materials under high pressure and high temperature.
      Synchrotron X-ray diffraction is one of the most powerful tools for studying
      phase stability and equation of state over a wide range of pressure and
      temperature conditions. Recently an experimental capability has been developed
      for simultaneous nuclear resonant scattering and X-ray diffraction measurements
      using synchrotron radiation. Here the application of this method to determine the
      sound velocities of compressed Fe(3)C is shown. The X-ray diffraction
      measurements allow detection of microscale impurities, phase transitions and
      chemical reactions upon compression or heating. They also provide information on
      sample pressure, grain size distribution and unit cell volume. By combining the
      Debye velocity extracted from the nuclear resonant inelastic X-ray scattering
      measurements and the structure, density and elasticity data from the X-ray
      diffraction measurements simultaneously obtained, more accurate sound velocity
      data can be derived. Our results on few-crystal and powder samples indicate
      strong anisotropy in the sound velocities of Fe(3)C under ambient conditions.

PMID- 19844005
TI  - Development of an energy-domain 57Fe-Mossbauer spectrometer using synchrotron
      radiation and its application to ultrahigh-pressure studies with a diamond anvil
      cell.
AB  - An energy-domain (57)Fe-Mossbauer spectrometer using synchrotron radiation (SR)
      with a diamond anvil cell (DAC) has been developed for ultrahigh-pressure
      measurements. The main optical system consists of a single-line pure nuclear
      Bragg reflection from an oscillating (57)FeBO(3) single crystal near the Neel
      temperature and an X-ray focusing device. The developed spectrometer can filter
      the Doppler-shifted single-line (57)Fe-Mossbauer radiation with a narrow
      bandwidth of neV order from a broadband SR source. The focused incident X-rays
      make it easy to measure a small specimen in the DAC. The present paper introduces
      the design and performance of the SR (57)Fe-Mossbauer spectrometer and its
      demonstrative applications including the newly discovered result of a pressure
      induced magnetic phase transition of polycrystalline (57)Fe(3)BO(6) and an
      unknown high-pressure phase of Gd(57)Fe(2) alloy placed in a DAC under high
      pressures up to 302 GPa. The achievement of Mossbauer spectroscopy in the
      multimegabar range is of particular interest to researchers studying the nature
      of the Earth's core.

PMID- 19844006
TI  - X-ray magnetic spectroscopy at high pressure: performance of SPring-8 BL39XU.
AB  - An X-ray magnetic circular dichroism experiment under multiple extreme
      conditions, 2 <or= T <or= 300 K, H <or= 10 T and P <or= 50 GPa, has been achieved
      at SPring-8 BL39XU. A combination of the high-brilliant X-ray beam and a helicity
      controlled technique enabled the dichroic signal to be recorded with high
      accuracy. The performance is shown by the outcome of pressure-induced
      ferromagnetism in Mn(3)GaC and the pressure-suppressed Co moment in ErCo(2). Two
      technical developments, a tiny diamond anvil cell inserted into a superconducting
      magnet and in situ pressure calibration using 90 degrees Bragg diffraction from a
      NaCl marker, are also presented. X-ray magnetic spectroscopy under multiple
      extreme conditions is now opening a new approach to materials science.

PMID- 19844007
TI  - Portable laser-heating system for diamond anvil cells.
AB  - The diamond anvil cell (DAC) technique coupled with laser heating has become the
      most successful method for studying materials in the multimegabar pressure range
      at high temperatures. However, so far all DAC laser-heating systems have been
      stationary: they are linked either to certain equipment or to a beamline. Here, a
      portable laser-heating system for DACs has been developed which can be moved
      between various analytical facilities, including transfer from in-house to a
      synchrotron or between synchrotron beamlines. Application of the system is
      demonstrated in an example of nuclear inelastic scattering measurements of
      ferropericlase (Mg(0.88)Fe(0.12))O and h.c.p.-Fe(0.9)Ni(0.1) alloy, and X-ray
      absorption near-edge spectroscopy of (Mg(0.85)Fe(0.15))SiO(3) majorite at high
      pressures and temperatures. Our results indicate that sound velocities of h.c.p.
      Fe(0.9)Ni(0.1) at pressures up to 50 GPa and high temperatures do not follow a
      linear relation with density.

PMID- 19844008
TI  - A combination of a Drickamer anvil apparatus and monochromatic X-rays for stress
      and strain measurements under high pressure.
AB  - A modified Drickamer anvil apparatus has been developed to combine with
      monochromatic synchrotron radiation for high-pressure X-ray diffraction and
      radiography in the GSECARS bending-magnet station, 13-BM-D, at the Advanced
      Photon Source, Argonne, USA. Using this experimental set-up, deformation
      experiments can be carried out at pressures in excess of 30 GPa at high
      temperatures. Differential stresses and total axial strains of polycrystalline
      platinum and Mg(2)SiO(4) ringwoodite have been measured up to 32 GPa at room
      temperature using tungsten carbide anvils. The total axial strain of the platinum
      increases with pressure and reaches about 55% at the highest pressure. A test run
      using a composite sintered diamond anvil system was performed. The use of X-ray
      tranparent anvils enables the entire Debye rings to be observed up to 10 degrees
      2theta. With high-energy photons (65-70 keV), this allows a coverage in Q (= 2pi
      sintheta/lambda) to about 3 A(-1), thus making it possible to evaluate
      hydrostatic pressure and differential stress in crystalline minerals using
      diffraction. This, coupled with the ability to determine axial strain, allows
      deformation studies to be performed to pressures above 30 GPa.

PMID- 19844009
TI  - In situ rheological measurements at extreme pressure and temperature using
      synchrotron X-ray diffraction and radiography.
AB  - Dramatic technical progress seen over the past decade now allows the plastic
      properties of materials to be investigated under extreme pressure and temperature
      conditions. Coupling of high-pressure apparatuses with synchrotron radiation
      significantly improves the quantification of differential stress and specimen
      textures from X-ray diffraction data, as well as specimen strains and strain
      rates by radiography. This contribution briefly reviews the recent developments
      in the field and describes state-of-the-art extreme-pressure deformation devices
      and analytical techniques available today. The focus here is on apparatuses
      promoting deformation at pressures largely in excess of 3 GPa, namely the diamond
      anvil cell, the deformation-DIA apparatus and the rotational Drickamer apparatus,
      as well as on the methods used to carry out controlled deformation experiments
      while quantifying X-ray data in terms of materials rheological parameters. It is
      shown that these new techniques open the new field of in situ investigation of
      materials rheology at extreme conditions, which already finds multiple
      fundamental applications in the understanding of the dynamics of Earth-like
      planet interior.

PMID- 19844010
TI  - Stress measurement under high pressure using Kawai-type multi-anvil apparatus
      combined with synchrotron radiation.
AB  - A system for stress measurement under high pressure has been developed at
      beamline BL04B1, SPring-8, Japan. A Kawai-type multi-anvil apparatus, SPEED-1500,
      was used to pressurize polycrystalline KCl to 9.9 GPa in a mechanically
      anisotropic cell assembly with the KCl sample sandwiched between dense Al(2)O(3)
      pistons. The variation of deviatoric stress was determined from the lattice
      distortion measured using two-dimensional X-ray diffraction with monochromatic
      synchrotron X-rays. The low-pressure B1 phase transformed to the high-pressure
      polymorph B2 during compression. The deviatoric stress increased with increasing
      pressure in both the B1 and B2 phases except for the two-phase-coexisting region
      at a pressure of 2-3 GPa. This new system provides one of the technical
      foundations for conducting precise rheological measurements at conditions of the
      Earth's lower mantle.

PMID- 19844011
TI  - A system for measuring elastic wave velocity under high pressure and high
      temperature using a combination of ultrasonic measurement and the multi-anvil
      apparatus at SPring-8.
AB  - An experimental system to measure the elastic wave velocities of hot-pressed
      polycrystalline samples at high pressure and high temperature has been installed
      at SPring-8. It uses a combination of the ultrasonic pulse-echo-overlap method
      and Kawai-type multi-anvil apparatus (SPEED-1500). X-ray radiographic imaging
      enables the sample length to be determined at high pressure and high temperature,
      which is indispensable for precise determination of elastic wave velocity.
      Precise measurements of the elastic wave velocities of various minerals have been
      determined at pressures up to 19 GPa and temperatures up to 1673 K. The
      experimental technique provides the precise elastic wave velocities of various
      materials corresponding to those in the Earth's mantle.

PMID- 19844012
TI  - Laser heating in diamond anvil cells: developments in pulsed and continuous
      techniques.
AB  - Developments in continuous and pulsed laser-heating techniques, and finite
      element calculations for diamond anvil cell experiments are reported. The methods
      involve the use of time-resolved (5 ns gated) incandescent light temperature
      measurements to determine the time dependence of heat fluxes, while near-IR
      incandescent light temperature measurements allow temperature measurements to as
      low as 500 K. Further optimization of timing in pulsed laser heating together
      with sample engineering will provide additional improvements in data collection
      in very high P-T experiments.

PMID- 19844013
TI  - Combined high pressure and heavy-ion irradiation: a novel approach.
AB  - Swift heavy-ion irradiations of a wide variety of materials have been used to
      modify and manipulate the properties of solids at the nanoscale. Recently, these
      high-energy irradiations have been successfully combined with high-pressure
      experiments. Based on results obtained for zircon (ZrSiO(4)), this paper
      introduces this new experimental approach involving diamond anvil cells and large
      ion-accelerator facilities. This technique provides a wide spectrum of geoscience
      applications from nanoscale simulations of fission-track formation under crustal
      conditions to phase transitions of radiation-damaged minerals resulting from
      meteorite impact.

PMID- 19844014
TI  - Linear polarization scans for resonant X-ray diffraction with a double-phase
      plate configuration.
AB  - An in-vacuum double-phase-plate diffractometer for performing polarization scans
      combined with resonant X-ray diffraction experiments is presented. The use of two
      phase plates enables the correction of some of the aberration effects owing to
      the divergence of the beam and its energy spread. A higher rate of rotated
      polarization is thus obtained in comparison with a system with only a single
      retarder. Consequently, thinner phase plates can be used to obtain the required
      rotated polarization rate. These results are particularly interesting for
      applications at low energy (e.g. 4 keV) where the absorption owing to the phase
      plate(s) plays a key role in the feasibility of these experiments. Measurements
      by means of polarization scans at the uranium M(4) edge on UO(2) enable the
      contributions of the magnetic and quadrupole ordering in the material to be
      disentangled.

PMID- 19844015
TI  - Use of a hexapod in diffraction measurements of substrate-supported crystals of
      organic semiconductors.
AB  - Thin films of organic semiconductor prepared on substrates generally contain
      crystals that have one common crystal plane parallel to the substrate but random
      in-plane orientations. In diffraction measurements of these structures, it is
      often required to anchor the X-ray beam on a fixed spot on the sample, such as an
      optically visible crystallite or island. Here, a hexapod is used in place of a
      traditional multi-circle diffractometer to perform area-detector-based
      diffraction measurements on an actual device that contains 6,13-bis(triisopropyl
      silyethynyl)-pentacene (TIPS-pentacene) crystals. The hexapod allows for sample
      rotations about any user-defined rotation center. Two types of complex sample
      motions have been programmed to characterize the structure of the TIPS-pentacene
      crystal: an in-plane powder average has been performed at a fixed grazing
      incident angle to determine the lattice parameters of the crystal; then the in
      plane component of the scattering vector was continuously rotated in transmission
      geometry to determine the local crystal orientation.

PMID- 19844016
TI  - Individual GaAs nanorods imaged by coherent X-ray diffraction.
AB  - Using scanning X-ray diffraction microscopy with a spot size of 220 x 600 nm, it
      was possible to inspect individual GaAs nanorods grown seed-free through circular
      openings in a SiN(x) mask in a periodic array with 3 microm spacing on
      GaAs[111]B. The focused X-ray beam allows the determination of the strain state
      of individual rods and, in combination with coherent diffraction imaging, it was
      also possible to characterize morphological details. Rods grown either in the
      centre or at the edge of the array show significant differences in shape, size
      and strain state.

PMID- 19844017
TI  - A decade of user operation on the macromolecular crystallography MAD beamline
      ID14-4 at the ESRF.
AB  - ID14-4 at the ESRF is the first tunable undulator-based macromolecular
      crystallography beamline that can celebrate a decade of user service. During this
      time ID14-4 has not only been instrumental in the determination of the structures
      of biologically important molecules but has also contributed significantly to the
      development of various instruments, novel data collection schemes and pioneering
      radiation damage studies on biological samples. Here, the evolution of ID14-4
      over the last decade is presented, and some of the major improvements that were
      carried out in order to maintain its status as one of the most productive
      macromolecular crystallography beamlines are highlighted. The experimental hutch
      has been upgraded to accommodate a high-precision diffractometer, a sample
      changer and a large CCD detector. More recently, the optical hutch has been
      refurbished in order to improve the X-ray beam quality on ID14-4 and to
      incorporate the most modern and robust optical elements used at other ESRF
      beamlines. These new optical elements will be described and their effect on beam
      stability discussed. These studies may be useful in the design, construction and
      maintenance of future X-ray beamlines for macromolecular crystallography and
      indeed other applications, such as those planned for the ESRF upgrade.

PMID- 19844018
TI  - Synchrotron study of oxygen depletion in a Bi-2212 whisker annealed at 363 K.
AB  - Direct evidence is reported of structural and electronic effects induced on a
      single Bi(2)Sr(2)CaCu(2)O(8+delta) (Bi-2212) whisker during a progressive
      annealing process. The crystal was investigated by micro X-ray diffraction (micro
      XRD), micro X-ray fluorescence and electrical characterization at the European
      Synchrotron Radiation Facility, during a series of three in situ thermal
      processes at 363 K. Each step increased the sample resistivity and decreased its
      critical temperature, up to a semiconducting behaviour. These data correlate with
      micro-XRD analysis, which shows an increase of the c-axis parameter from 30.56 A
      to 30.75 A, indicating an oxygen depletion mechanism. Mild temperature annealing
      could be an effective process to modulate the intrinsic Josephson junctions'
      characteristics in Bi-2212 whiskers.

PMID- 19844019
TI  - I18--the microfocus spectroscopy beamline at the Diamond Light Source.
AB  - The design and performance of the microfocus spectroscopy beamline at the Diamond
      Light Source are described. The beamline is based on a 27 mm-period undulator to
      give an operable energy range between 2 and 20.7 keV, enabling it to cover the K
      edges of the elements from P to Mo and the L(3)-edges from Sr to Pu. Micro-X-ray
      fluorescence, micro-EXAFS and micro-X-ray diffraction have all been achieved on
      the beamline with a spot size of approximately 3 microm. The principal optical
      elements of the beamline consist of a toroid mirror, a liquid-nitrogen-cooled
      double-crystal monochromator and a pair of bimorph Kirkpatrick-Baez mirrors. The
      performance of the optics is compared with theoretical values and a few of the
      early experimental results are summarized.

PMID- 19844020
TI  - In situ synchrotron high-energy X-ray diffraction analysis on phase
      transformations in Ti-Al alloys processed by equal-channel angular pressing.
AB  - Mixtures of 47-Al and 53-Ti powders (atomic %) have been consolidated using back
      pressure equal-channel angular pressing starting with both raw and ball-milled
      powders. In situ synchrotron high-energy X-ray diffraction studies are presented
      with continuous Rietveld analysis obtained upon a heating ramp from 300 K to 1075
      K performed after the consolidation process. Initial phase distributions contain
      all intermetallic compounds of this system except Al, with distribution maxima in
      the outer regions of the concentrations (alpha-Ti, TiAl(3)). Upon annealing, the
      phase evolution and lattice parameter changes owing to chemical segregation,
      which is in favour for the more equilibrated phases such as gamma-TiAl, alpha(2)
      Ti(3)Al and TiAl(2), were followed unprecedentedly in detail. An initial delta
      TiH(2) content with a phase transition at about 625 K upon heating created an
      intermediate beta-Ti phase which played an important role in the reaction chain
      and gradually transformed into the final products.

PMID- 19844021
TI  - DISCO: a low-energy multipurpose beamline at synchrotron SOLEIL.
AB  - DISCO, a novel low-energy beamline covering the spectrum range from the VUV to
      the visible, has received its first photons at the French synchrotron SOLEIL. In
      this article the DISCO design and concept of three experimental stations serving
      research communities in biology and chemistry are described. Emphasis has been
      put on high flux generation and preservation of polarization at variable energy
      resolutions. The three experiments include a completely new approach for
      microscopy and atmospheric pressure experiments as well as a ;classical'
      synchrotron radiation circular dichroism station. Preliminary tests of the
      optical design and technical concept have been made. Theoretical predictions of
      the beam have been compared with the first images produced by the first photons
      originating from the large-aperture bending-magnet source. Results are also
      reported concerning the cold finger used to absorb hard X-ray radiation in the
      central part of the synchrotron beam and to avoid heavy thermal load on the
      following optics. Wavelength selection using monochromators with different
      gratings for each experimental set-up as well as beam propagation and
      conditioning throughout the optical system are detailed. First photons comply
      very well with the theoretical calculations.

PMID- 19844022
TI  - Design and application of a high-temperature microfurnace for an in situ X-ray
      diffraction study of phase transformation.
AB  - Thermal treatment of mineral ores such as ilmenite can initiate phase
      transformations that could affect their activation or deactivation, subsequently
      influencing their ability to dissolve in a leaching agent. Most laboratory-based
      X-ray diffraction (XRD) studies were carried out ex situ in which realistic
      diffraction patterns could not be obtained simultaneously with occurring
      reactions and were time-consuming. The availability of synchrotron-radiation
      based XRD not only allows in situ analysis, but significantly shortens the data
      recording time. The present study details the design of a robust high-temperature
      microfurnace which allows thermal processing of mineral ore samples and the
      simultaneous collection of high-resolution synchrotron XRD data. In addition, the
      application of the manufactured microfurnace for in situ study of phase
      transformations of ilmenite ore under reducing conditions is demonstrated.

PMID- 19844023
TI  - X-ray pair distribution function analysis of nanostructured materials using a
      Mythen detector.
AB  - Total scattering from nanocrystalline materials recorded on the Australian
      Synchrotron powder diffraction beamline has been analysed to produce atomic pair
      distribution functions (PDFs) for structural analysis. The capability of this
      beamline, which uses the massively parallel Mythen II detector, has been
      quantified with respect to PDF structure analysis. Data were recorded to a
      wavevector magnitude, Q, of 20.5 A(-1), with successful PDFs obtained for
      counting times as short as 10 s for crystalline LaB(6) and 180 s for
      nanocrystalline (47 A) anatase. This paper describes the aspects of a PDF
      experiment that are crucial to its success, with reference to the outcomes of
      analysis of data collected from nanocrystalline TiO(2) and microcrystalline
      LaB(6) and IrO(2).

PMID- 19844024
TI  - Developing VUV spectroscopy for protein folding and material luminescence on
      beamline 4B8 at the Beijing Synchrotron Radiation Facility.
AB  - The new 4B8 beamline provides UV-VUV light in the wavelength range from 360 to
      120 nm. It uniquely enables two kinds of spectroscopy measurements: synchrotron
      radiation circular dichroism spectroscopy and VUV excited fluorescence
      spectroscopy. The former is mainly used in protein secondary structure studies,
      and the latter in VUV excited luminescent materials research. Remote access to
      fluorescence measurement has been realised and users can collect data online.
      Besides steady-state measurements, fluorescence lifetime measurements have been
      established using the time domain method, while a laser-induced temperature jump
      is under development for protein folding dynamics using circular dichroism as a
      probe.

PMID- 19844025
TI  - On the neglecting of higher-order cumulants in EXAFS data analysis.
AB  - The cumulant expansion is one of the most powerful and useful methods for EXAFS
      data analysis, in which the higher-order cumulants allow to consider deviations
      from a simple Gaussian distribution. In this work, analytical expressions have
      been derived to show the effects of neglecting higher-order cumulants in EXAFS
      analysis by the ratio method. The errors in the best-fitting procedure owing to
      the omission of the higher-order cumulants, as well as of the coordination
      number, can be determined.

PMID- 19844026
TI  - New agitated and thermostatized cell for in situ monitoring of fast reactions by
      synchrotron SAXS.
AB  - A thermostatized and agitated sample cell for synchrotron small-angle X-ray
      scattering (SAXS) measurements of liquid samples (homogeneous or heterogeneous)
      has been developed. The cell is composed of a compact main body with inlet and
      outlet windows for the beams of light. The volume of the cell is approximately
      0.8 ml and the distance between the windows is 5 mm to allow accurate SAXS
      measurements. The cell is thermostatized by means of a jacket that surrounds the
      sample holder and it is connected to a thermostatic bath. In addition, the cell
      has a top and a bottom lid that allow easy cleaning and maintenance without
      demounting the optical windows. The cell has been used to run SAXS measurements
      of liquid samples and, for the first time, a mini-emulsion polymerization
      reaction has been monitored by SAXS.

PMID- 19844027
TI  - EDNA: a framework for plugin-based applications applied to X-ray experiment
      online data analysis.
AB  - EDNA is a framework for developing plugin-based applications especially for
      online data analysis in the X-ray experiments field. This article describes the
      features provided by the EDNA framework to ease the development of extensible
      scientific applications. This framework includes a plugins class hierarchy,
      configuration and application facilities, a mechanism to generate data classes
      and a testing framework. These utilities allow rapid development and integration
      in which robustness and quality play a fundamental role. A first prototype,
      designed for macromolecular crystallography experiments and tested at several
      synchrotrons, is presented.

PMID- 19844029
TI  - Structure determination without Fourier inversion. V. A concept based on
      parameter space.
AB  - The parameter-space concept for solving crystal structures from reflection
      amplitudes (without employing or searching for their phases) is described on a
      theoretically oriented basis. Emphasis is placed on the principles of the method,
      on selecting one of three types of parameter spaces discussed in this paper, and
      in particular on the structure model employed (equal-atom point model, however
      usually reduced to one-dimensional projections) and on the system of
      'isosurfaces' representing experimental 'geometrical structure amplitudes' in an
      orthonormal parameter space of as many dimensions as unknown atomic coordinates.
      The symmetry of the parameter space as well as of the imprinted isosurfaces and
      its effect on solution methods is discussed. For point atoms scattering with
      different phases or signs (as is possible in the case of X-ray resonant or of
      neutron scattering) it is demonstrated that the 'landscape' of these isosurfaces
      remains invariant save certain shifts of origin known beforehand (under the
      condition that all atomic scattering amplitudes have been reduced to 1 thus
      meeting the requirement of the structure model above). Partly referring to
      earlier publications on the subject, measures are briefly described which permit
      circumventing an analytical solution of the system of structure-amplitude
      equations and lead to either a unique (unequivocal) approximate structure
      solution (offering rather high spatial resolution) or to all possible solutions
      permitted by the experimental data used (thus including also all potential 'false
      minima'). A simple connection to Patterson vectors is given, also a first hint on
      data errors. References are given for practical details of various solution
      techniques already tested and for reconstruction of three-dimensional structures
      from their projections by 'point tomography'. We would feel foolish if we tried
      to aim at any kind of 'competition' to existing methods. Having mentioned 'pros
      and cons' of our concept, some ideas about potential applications are
      nevertheless offered which are mainly based on its inherent resolution power
      though demanding rather few reflection data (use of optimal intensity contrast
      included) and possibly providing a result proven to be unique.

PMID- 19844030
TI  - On symmetry classes of crystal structures.
AB  - An open-ended classification scheme for crystal structures based on Wyckoff sets
      and affine normalizer groups is proposed. It is free of metrical and geometrical
      considerations. All structures of one structure type belong to the same symmetry
      class. An application is given for the Inorganic Crystal Structure Database
      (version 2, 2007).

PMID- 19844031
TI  - Multiresolution of quasicrystal diffraction spectra.
AB  - A method for analyzing and classifying two-dimensional pure point diffraction
      spectra (i.e. a set of Bragg peaks) of certain self-similar structures with
      scaling factor beta > 1, such as quasicrystals, is presented. The two-dimensional
      pure point diffraction spectrum Pi is viewed as a point set in the complex plane
      in which each point is assigned a positive number, its Bragg intensity. Then, by
      using a nested sequence of self-similar subsets called beta-lattices, we
      implement a multiresolution analysis of the spectrum Pi. This analysis yields a
      partition of Pi simultaneously in geometry, in scale and in intensity (the
      'fingerprint' of the spectrum, not of the diffracting structure itself). The
      method is tested through numerical explorations of pure point diffraction spectra
      of various mathematical structures and also with the diffraction pattern of a
      realistic model of a quasicrystal.

PMID- 19844032
TI  - Experimental charge-density study of paracetamol--multipole refinement in the
      presence of a disordered methyl group.
AB  - A high-resolution single-crystal X-ray study of paracetamol has been performed at
      85 K. Different approaches to modeling the experimental electron density (ED)
      were tested for the dynamically disordered portions of the molecule in order to
      check to what extent it is possible to obtain a proper ED distribution in the
      ordered part. Models were examined in which the methyl-group ED was built from
      pseudoatoms taken from the University at Buffalo Pseudoatom Databank or the
      Invariom database, with multipole parameters for the remaining atoms being
      obtained from free refinement. The kappa' restricted multipolar model (KRMM) and
      free kappa' refinements were compared; restriction of the kappa' parameters was
      essential in order to obtain values of the electrostatic interaction energy
      consistent with the results of theoretical single-point periodic calculations.
      After simultaneous use of KRMM refinement and the databases to model the methyl
      group, the bond critical point properties and interaction electrostatic energy
      values were found to be closer to those obtained from theory. Additionally, some
      discrepancies in the ED distribution and dipole moment among transferred
      aspherical atom model refinements utilizing both theoretical databases and
      parameters from theoretical periodic calculations are shown. Including the
      influence of the crystal field in the periodic calculations increases the ED in
      the hydroxyl and amide groups, thus leading to higher values of the electrostatic
      interaction energy, changes in the electrostatic potential values mapped on the
      isodensity surface and changes in the shape of the anisotropic displacement
      parameters with respect to results found for both database models.

PMID- 19844033
TI  - The OD interpretation of the crystal structure of kettnerite CaBiOFCO3.
AB  - The mineral kettnerite, CaBi(OFCO(3)), is a rare example of an order-disorder
      (OD) structure with a quadratic net. The lattice parameters of the simplest
      possible 1O polytype are a = 5.3641 (1), b = 5.3641 (1), c = 13.5771 (2) A, and
      the space group is Pbaa. There are three kinds of OD layers, identical to
      structure-building layers. Two of them are non-polar: the Bi-O and Ca-F at z = 0
      and z = 1/2, respectively, with the layer-group symmetry
      C2/m2/m(4/a,b)2(1)/m2(1)/m. The third kind of OD layer of CO(3) groups (located
      between the Bi-O and Ca-F layers) is polar, with alternating sense of polarity.
      The layer group is Pba(4)mm. Triangular CO(3) groups are parallel to (110) or
      (110) planes with one O atom oriented towards the Bi-O layer and the remaining
      two O atoms oriented towards the Ca-F layer. The orientations of CO(3) groups
      alternate along the [110] and [110] directions. As a result, each group parallel
      to (110) is surrounded by four nearest neighbors parallel to (110) and vice
      versa. These positions can be interchanged by an (a + b)/2 shift or by pi/2
      rotation; thus stacking of the layer onto adjacent ones is ambiguous. Instead of
      OD layers, the polytypes are generated by stacking of OD packets, comprising the
      whole CO(3) layers and adjacent halves of the Bi-O and Ca-F layers. They are
      polar, with alternating sense of polarity; the layer group is Pba(4)mm. Stacking
      sequences are expressed by ball-and-stick models, with the aid of symbolic
      figures, and by sequences of orientational characters. There are two maximum
      degree-of-order (MDO) polytypes, 1O (really found and described, see lattice
      parameters and space group above) and 2O, with doubled c parameter and space
      group Ibca (not yet found). The derivation of the MDO generating operations of
      both polytypes is presented in this paper. The stacking rule also allows another,
      non-MDO, polytype with doubled c, i.e. the 2Q polytype, space group P4(2)bc
      (tetragonal, not yet found). Various kinds of domains can exist: (i) out-of-step
      domains shifted by (a + b)/2, (ii) twin domains rotated by pi/2 around local
      tetrads of odd or even packets, and (iii) upside-down domains in the polar 2Q
      polytype. Stacking sequences of 16 possible domains of the polytypes mentioned
      above are listed. Also 60 domains of four distinct six-packet polytypes are
      theoretically possible.

PMID- 19844034
TI  - Molecular replacement: the probabilistic approach of the program REMO09 and its
      applications.
AB  - The method of joint probability distribution functions has been applied to
      molecular replacement techniques. The rotational search is performed by rotating
      the reciprocal lattice of the protein with respect to the calculated transform of
      the model structure; the translation search is performed by fast Fourier
      transform. Several cases of prior information are studied, both for the rotation
      and for the translation step: e.g. the conditional probability density for the
      rotation or the translation of a monomer is found both for ab initio and when the
      rotation and/or the translation values of other monomers are given. The new
      approach has been implemented in the program REMO09, which is part of the package
      for global phasing IL MILIONE [Burla, Caliandro, Camalli, Cascarano, De Caro,
      Giacovazzo, Polidori, Siliqi & Spagna (2007). J. Appl. Cryst. 40, 609-613]. A
      large set of test structures has been used for checking the efficiency of the new
      algorithms, which proved to be significantly robust in finding the correct
      solutions and in discriminating them from noise. An important design concept is
      the high degree of automatism: REMO09 is often capable of providing a reliable
      model of the target structure without any user intervention.

PMID- 19844035
TI  - Improving the direct-methods sign-unconstrained S-FFT algorithm. XV.
AB  - In order to extend the application field of the direct-methods S-FFT phase
      refinement algorithm to density functions with positive and negative peaks, the
      equal-sign constraint was removed from its definition by combining rho(2) with an
      appropriate density function mask [Rius & Frontera (2008). Acta Cryst. A64, 670
      674]. This generalized algorithm (S(2)-FFT) was shown to be highly effective for
      crystal structures with at least one moderate scatterer in the unit cell but less
      effective when applied to structures with only light scatterers. To increase the
      success rate in this second case, the mask has been improved and the convergence
      rate of S(2)-FFT has been investigated. Finally, a closely related but simpler
      phase-refinement function (S(m)) combining rho (instead of rho(2)) with a new
      mask is introduced. For simple cases at least this can also treat density peaks
      in the absence of the equal-sign constraint.

PMID- 19844036
TI  - Multiplicative congruential generators, their lattice structure, its relation to
      lattice-sublattice transformations and applications in crystallography.
AB  - An analysis of certain types of multiplicative congruential generators--otherwise
      known for their application to the sequential generation of pseudo-random numbers
      -reveals their relation to the coordinate description of lattice points in two
      dimensional primitive sublattices. Taking the index of the lattice-sublattice
      transformation as the modulus of the multiplicative congruential generator, there
      are special choices for its multiplier which induce a symmetry-preserving
      permutation of lattice-point coordinates. From an analysis of similar sublattices
      with hexagonal and square symmetry it is conjectured that the cycle structure of
      the permutation has its crystallographic counterpart in the description of
      crystallographic orbits. Some applications of multiplicative congruential
      generators in structural chemistry and biology are discussed.

PMID- 19844040
TI  - Wastewater treatment modelling: dealing with uncertainties.
AB  - This paper serves as a problem statement of the issues surrounding uncertainty in
      wastewater treatment modelling. The paper proposes a structure for identifying
      the sources of uncertainty introduced during each step of an engineering project
      concerned with model-based design or optimisation of a wastewater treatment
      system. It briefly references the methods currently used to evaluate prediction
      accuracy and uncertainty and discusses the relevance of uncertainty evaluations
      in model applications. The paper aims to raise awareness and initiate a
      comprehensive discussion among professionals on model prediction accuracy and
      uncertainty issues. It also aims to identify future research needs. Ultimately
      the goal of such a discussion would be to generate transparent and objective
      methods of explicitly evaluating the reliability of model results, before they
      are implemented in an engineering decision-making context.

PMID- 19844041
TI  - Activated sludge modelling in practice: an international survey.
AB  - The Good Modelling Practice Task Group (GMP-TG) of the International Water
      Association (IWA) is developing guidelines for the use of Activated Sludge Models
      (ASM). As part of this work the group created and sent out a questionnaire to
      current and potential activated sludge model users in 2007. The objectives of the
      questionnaire were (i) to better define the profile of ASM users, (ii) to
      identify the tools and procedures that are actually used and (iii) to highlight
      the main limitations while building and using ASM-type models. Ninety-six answers
      were received from all over the world, from several types of organisation. The
      results were analysed to identify the modellers' perceptions of models depending
      on their profile. The results also highlighted the main topics of interest for
      improving modelling procedures which are standardisation of the available
      modelling guidelines and better experience and knowledge transfer.

PMID- 19844042
TI  - Optimisation potential for a SBR plant based upon integrated modelling for dry
      and wet weather conditions.
AB  - Integrated dynamic simulation analysis of a full-scale municipal sequential batch
      reactor (SBR) wastewater treatment plant (WWTP) was performed using the KOSMO
      pollution load simulation model for the combined sewer system (CSS) and the ASM3
      + EAWAG-BioP model for the WWTP. Various optimising strategies for dry and storm
      weather conditions were developed to raise the purification and hydraulic
      performance and to reduce operation costs based on simulation studies with the
      calibrated WWTP model. The implementation of some strategies on the plant led to
      lower effluent values and an average annual saving of 49,000 euro including
      sewage tax, which is 22% of the total running costs. Dynamic simulation analysis
      of CSS for an increased WWTP influent over a period of one year showed high
      potentials for reducing combined sewer overflow (CSO) volume by 18-27% and CSO
      loads for COD by 22%, NH(4)-N and P(total) by 33%. In addition, the SBR WWTP
      could easily handle much higher influents without exceeding the monitoring
      values. During the integrated simulation of representative storm events, the
      total emission load for COD dropped to 90%, the sewer system emitted 47% less,
      whereas the pollution load in the WWTP effluent increased to only 14% with 2%
      higher running costs.

PMID- 19844043
TI  - Anaerobic digestion of the organic fraction of municipal solid waste in a two
      stage membrane process.
AB  - A batch of the Organic Fraction of Municipal Solid Waste (OFMSW) was treated in a
      two-step process with effluent recirculation comprising a novel hydrolytic
      reactor (HR) followed by a Submerged Anaerobic Membrane Bioreactor (SAMBR)
      operating at a stable permeate flux of 5.6 L/m(2) hr (LMH). A soluble COD removal
      higher than 95% was obtained from the SAMBR. The soluble COD as well as the Total
      Suspended Solids (TSS) did not build up due to efficient hydrolysis inside the
      SAMBR, and no VFA accumulation occurred due to the complete retention of
      methanogens by the membrane as well as the formation of syntrophic associations.
      Because of the microfiltration membrane in the second reactor a stabilized
      leachate was obtained from the very first days of the treatment and the highly
      stable process enabled shorter treatment periods compared to traditional leach
      bed processes. This experiment showed that the recycle of the stabilised leachate
      does not lead to a build up of SCOD. Size exclusion chromatography analysis
      confirmed that high molecular weight compounds were completely degraded and did
      not appear in the SAMBR permeate, and that low molecular weight fulvic-like and
      medium MW material were present in the permeate of the SAMBR but their
      concentration remained stable with time.

PMID- 19844044
TI  - Integrated monitoring of South Portugal water bodies: a methodology towards WFD.
AB  - The challenge on implementation of the EU Water Framework Directive (WFD)
      (2000/60/EC) fosters the development of new monitoring approaches. The directive
      promotes the use of modelling techniques to assist all phases of the process,
      from characterization and establishment of reference conditions to identification
      of pressures and assessment of impact. This work is based on the above
      principles. A classical monitoring of the water status of the main transitional
      water bodies of Algarve (South of Portugal) is combined with advanced in situ
      water profiling and hydrodynamic, water quality and ecological modelling to build
      a complete description of the system. The aim is to demonstrate a methodology
      where traditional monitoring and modelling tools can be joined together to draw a
      holistic picture. The results show that globally the water bodies present a good
      trophic status. Eutrophication symptoms are not generalized. Due to physical
      transport and dispersion, nutrient enrichment is not the only factor limiting
      growth; residence time is also an important factor. Some confined regions with
      high residence times are at present endangered by point and diffuse sources of
      pollution. The microbiologic impact of waste water treatment plants (WWTP) is
      confined to regions between 500 m and 1 km from the discharges.

PMID- 19844045
TI  - Wet air and catalytic wet air oxidation of several azodyes from wastewaters: the
      beneficial role of catalysis.
AB  - Degradation of several azo dyes, Acid Orange 7 (AO7), Acid Orange 74 (AO74),
      Direct Blue 71 (DB71), Reactive Black 5 (RB5) and Eriochrome Blue Black B (EBBB),
      well-known non-biodegradable mono, di and tri azo dyes has been studied using,
      wet-air oxidation (WAO) and catalytic wet air oxidation (CWAO). The efficiency of
      substrate decolorization and mineralization in each process has been
      comparatively discussed by evolution concentration, chemical oxygen demand, total
      organic carbon content and toxicity of dyes solutions. The most efficient method
      on decolorization and mineralization (TOC) was observed to be CWAO process.
      Mineralization efficiency with wet air and catalytic wet air oxidation essays was
      observed in the order of mono-azo > di-azo > tri-azo dye. Final solutions of CWAO
      applications after 180 min treatment can be disposed safely to environment.

PMID- 19844046
TI  - Design and configuration criteria for wetland systems treating greywater.
AB  - Design and configuration for wetlands treating greywater are usually based on
      literature data obtained from domestic wastewater operating wetlands. It is very
      important to determine proper criteria for design and configuration to provide
      efficiency and minimum maintenance, avoiding bad odour and clogging amongst
      others, ensuring the acceptance of householders. The aim of this work was to
      design a wetland system treating greywater for a household and determine whether
      the chosen criteria were appropriate. Some of the criteria taken into
      consideration for design and configuration were: quantitative and qualitative
      characteristics, desired removal of biochemical oxygen demand (BOD) and suspended
      solids (TSS), substrate and ornamental aspect of the system. The system was
      composed of a grease trap (kitchen), sedimentation tank, a horizontal flow
      constructed wetland (HF-CW), intermittent feeding system, and a vertical flow
      constructed wetland (VF-CW). The results showed that the suggested design and
      configuration were in accordance with the expected efficiency. Being a compact
      system, it was susceptible to peak flows, temporarily deteriorating the
      performance of the HF-CW. The hybrid system, however, showed to cope well with
      influent fluctuations. The overall performance of the system shows that the
      removal of turbidity, TSS, COD and BOD were over 88%, reaching 95% removal for
      both BOD and turbidity.

PMID- 19844047
TI  - Using remotely sensed imagery to estimate potential annual pollutant loads in
      river basins.
AB  - Land cover changes around river basins have caused serious environmental
      degradation in global surface water areas, in which the direct monitoring and
      numerical modeling is inherently difficult. Prediction of pollutant loads is
      therefore crucial to river environmental management under the impact of climate
      change and intensified human activities. This research analyzed the relationship
      between land cover types estimated from NOAA Advanced Very High Resolution
      Radiometer (AVHRR) imagery and the potential annual pollutant loads of river
      basins in Japan. Then an empirical approach, which estimates annual pollutant
      loads directly from satellite imagery and hydrological data, was investigated.
      Six water quality indicators were examined, including total nitrogen (TN), total
      phosphorus (TP), suspended sediment (SS), Biochemical Oxygen Demand (BOD),
      Chemical Oxygen Demand (COD), and Dissolved Oxygen (DO). The pollutant loads of
      TN, TP, SS, BOD, COD, and DO were then estimated for 30 river basins in Japan.
      Results show that the proposed simulation technique can be used to predict the
      pollutant loads of river basins in Japan. These results may be useful in
      establishing total maximum annual pollutant loads and developing best management
      strategies for surface water pollution at river basin scale.

PMID- 19844048
TI  - Distinguishing Stage 1 and 2 reverse osmosis permeates using fluorescence
      spectroscopy.
AB  - Fluorescence excitation-emission matrix (EEM) spectroscopy was used to
      distinguish between two stages of reverse osmosis (RO) permeates as the first
      step towards investigating the potential application of fluorescence as a
      monitoring tool for membrane performance. The signal response of several
      fluorescence peaks present in Stage 1 and Stage 2 RO permeates of an advanced
      water treatment plant were compared. The humic-like fluorescence region was found
      to have the largest percentage difference between stages and therefore was the
      most appropriate for enabling differentiation. Increases in humic-like
      fluorescence did not correlate with increases in conductivity or dissolved
      organic carbon measurements. This suggests that fluorescence is a more selective
      and sensitive method for monitoring the organic composition of RO permeates than
      established methods. Fluorescence is therefore a promising tool for improved
      water quality monitoring of RO permeates.

PMID- 19844049
TI  - Effect of ultrasound on particle surface charge and filterability during sludge
      anaerobic digestion.
AB  - The goal of this study was to follow and compare dewaterability parameters of
      untreated and "pre-sonicated" sludge during semicontinuous anaerobic digestion by
      particle charge density and sludge filterability measurements. Floc
      disintegration due to sonication resulted in a significant increase of soluble
      COD and colloidal charge density. It is interesting to note that in all the tests
      despite the higher specific charge density and soluble COD values of the
      sonicated feed, the digested sludge at steady state present in both reactors
      statistically comparable values, independently on the pretreatment. The
      biological hydrolysis of the untreated sludge causes a large release of dispersed
      charged fines whereas the digestion of the sonicated sludge is characterized by a
      significant removal of fines and colloids already present in the pretreated feed.
      The amelioration of the filterability during the digestion of the sonicated
      sludge in test #2 suggest that anaerobic digestion may be very effective for
      degrading fine dispersed particles produced by mechanical pre-hydrolysis.
      Nevertheless, ultrasound pre-treatment does not improve the dewaterability of the
      digested sludge with respect to the untreated one. Optimisation of both
      disintegration degree and hydraulic residence time is necessary to improve the
      dewaterability of the digested sonicated sludge.

PMID- 19844050
TI  - A new rule generation method to develop a decision support system for integrated
      management at river basin scale.
AB  - The Besos River Basin authority is working towards the implementation of
      integrated river basin management, as required by the Water Framework Directive
      (WFD), to achieve a good ecological and chemical status of all water bodies by
      2015. The studied system is constituted by two communities (La Garriga and
      Granollers), their corresponding draining catchments, sewer systems and two
      WWTPs, which discharge treated water at different locations of the same river.
      Within this context, the realisation of an integrated model of the river stretch
      and of the two WWTPs with their sewer systems and draining catchments was
      necessary. Such a model allows to efficiently simulate and analyse the behaviour
      of the integrated system and to optimize its performance holistically. In this
      article, a method is presented to generate rules to be implemented in a
      supervisory system for automatic management of the Integrated Urban Wastewater
      System (IUWS) in dry and storm weather. This is achieved by identifying, with the
      help of Monte Carlo simulations, the most performing operational parameters
      according to environmental and economic criteria-for the two weather conditions.

PMID- 19844051
TI  - Application of water quality index for assessment of surface water quality
      surrounding integrated industrial estate-Pantnagar.
AB  - Water pollution as a consequence of accelerated industrial growth has drawn
      concerns over public health and environment. In order to assess the extent of
      environmental impact due to integrated industrial estate-Pantnagar (IIE
      Pantnagar), surface water was monitored for duration of one year. Grab surface
      water samples from 12 locations were collected, processed and analyzed for 11 pre
      identified variables. Besides providing the raw baseline data, the information
      was normalized and integrated by applying Water Quality Index (WQI). The average
      surface water quality surrounding IIE-Pantnagar was found to be satisfactory in
      terms of its potability after conventional treatment and disinfection. During
      summer season, the WQI of Baigul River at Haldi Road illustrated good water
      quality (83.3), which however, deteriorates in its downstream at Rudrapur (55.5),
      signifying moderate quality. The WQI inside IIE-Pantnagar varied from 47.4 to
      66.6, revealing moderate to good surface water quality. However, in monsoon and
      post-monsoon seasons, WQI demonstrated a modest increase in quality for all
      sampling points, with a few exceptions due to dilution caused by monsoonal
      rainfall. In this period, average WQI varied from 49.6 to 81.7. During winter
      season, WQI further declined due to cumulative effects of industrial discharge
      from IIE-Pantnagar and other adjacent industrial set-ups coupled with municipal
      waste water from Rudrapur city. The lowest WQI for entire sampling network was
      found within IIE-Pantnagar as 37.1, revealing poor water quality. The application
      of WQI to assess temporal variations in surface water quality was therefore found
      satisfactory.

PMID- 19844052
TI  - Development of instrumentation systems as a base for control of digestion process
      stability in full-scale agricultural and industrial biogas plants.
AB  - This article deals with the analysis of instrumentation from three modern German
      full-scale biogas plants with different inputs and typical process engineering
      concepts for German conditions. The measured results from each plant and the
      suitability of the instrumentation used are evaluated and assessed. Conclusions
      are also made about improving the use and architecture of the instrumentation.
      The analysis results show which benefits and optimum combination of on-line and
      off-line instrumentation could result for the control and automation of
      industrial and agricultural biogas plants.

PMID- 19844053
TI  - The HSG procedure for modelling integrated urban wastewater systems.
AB  - Whilst the importance of integrated modelling of urban wastewater systems is ever
      increasing, there is still no concise procedure regarding how to carry out such
      modelling studies. After briefly discussing some earlier approaches, the
      guideline for integrated modelling developed by the Central European Simulation
      Research Group (HSG - Hochschulgruppe) is presented. This contribution suggests a
      six-step standardised procedure to integrated modelling. This commences with an
      analysis of the system and definition of objectives and criteria, covers
      selection of modelling approaches, analysis of data availability, calibration and
      validation and also includes the steps of scenario analysis and reporting. Recent
      research findings as well as experience gained from several application projects
      from Central Europe have been integrated in this guideline.

PMID- 19844054
TI  - Gold coast seaway smartrelease decision support system: optimising recycled water
      release in a sub tropical estuarine environment.
AB  - Gold Coast Water is responsible for the management of the water, recycled water
      and wastewater assets of the City of the Gold Coast on Australia's east coast.
      Excess treated recycled water is released at the Gold Coast Seaway, a man-made
      channel connecting the Broadwater Estuary with the Pacific Ocean, on an outgoing
      tide in order for the recycled water to be dispersed before the tide changes and
      re-enters the Broadwater estuary. Rapid population growth has placed increasing
      demands on the city's recycled water release system and an investigation of the
      capacity of the Broadwater to assimilate a greater volume of recycled water over
      a longer release period was undertaken in 2007. As an outcome, Gold Coast Water
      was granted an extension of the existing release licence from 10.5 hours per day
      to 13.3 hours per day from the Coombabah wastewater treatment plant (WWTP). The
      Seaway SmartRelease Project has been designed to optimise the release of the
      recycled water from the Coombabah WWTP in order to minimise the impact to the
      receiving estuarine water quality and maximise the cost efficiency of pumping. In
      order achieve this; an optimisation study that involves intensive hydrodynamic
      and water quality monitoring, numerical modelling and a web-based decision
      support system is underway. An intensive monitoring campaign provided information
      on water levels, currents, winds, waves, nutrients and bacterial levels within
      the Broadwater. This data was then used to calibrate and verify numerical models
      using the MIKE by DHI suite of software. The Decision Support System will then
      collect continually measured data such as water levels, interact with the WWTP
      SCADA system, run the numerical models and provide the optimal time window to
      release the required amount of recycled water from the WWTP within the licence
      specifications.

PMID- 19844055
TI  - Understanding the partitioning processes of mobile lead in soakaway sediments
      using sequential extraction and isotope analysis.
AB  - Lead (Pb) isotopic data were used in this study to first distinguish the
      partitioning of anthropogenic and natural lead in different fractions, obtained
      by BCR sequential extraction, and then to anticipate their mixing process in the
      soakaway sediment of artificial infiltration facilities (AIF). Total metal
      content was found higher in soakaway sediment samples than that of soil. The
      lowest (206)Pb/(207)Pb ratios were mostly observed in exchangeable fractions of
      soil and sediment samples, while residual fractions mostly showed the highest
      (206)Pb/(207)Pb and (208)Pb/(207)Pb ratios than those of other fractions. In
      general, both ratios were higher in the soil than those of sediments. Further
      among soil samples, residual fraction of bottom soil exhibited higher ratios than
      surface soil indicating higher contribution of natural lead with depth. In
      addition, the difference in Pb content, partitioning and its isotope signature
      among four sediment samples were also investigated considering their sampling
      locations. The plot of (206)Pb/(207)Pb versus (208)Pb/(207)Pb showed two well
      demarcated cluster formations by soil and sediments samples that describe the
      partitioning between anthropogenic and natural lead; and some points falling in
      between soil and sediment samples pertinently illustrated the mixing processes
      between these two different pools of lead.

PMID- 19844056
TI  - Evaluation of plant-wide WWTP control strategies including the effects of
      filamentous bulking sludge.
AB  - The main objective of this paper is to evaluate the effect of filamentous bulking
      sludge on the predicted performance of simulated plant-wide WWTP control
      strategies. First, as a reference case, several control strategies are
      implemented, simulated and evaluated using the IWA Benchmark Simulation Model No.
      2 (BSM2). In a second series of simulations the parameters of the secondary
      settler model in the BSM2 are automatically changed on the basis of an on-line
      calculated risk of filamentous bulking, in order to mimic the effect of growth of
      filamentous bacteria in the plant. The results are presented using multivariate
      analysis. Including the effects of filamentous bulking in the simulation model
      gives a-more realistic-deterioration of the plant performance during periods when
      the conditions for development of filamentous bulking sludge are favourable:
      compared to the reference case where bulking effects are not considered. Thus,
      there is a decrease of the overall settling velocity, an accumulation of the
      total suspended solids (TSS) in the middle layers of the settler with a
      consequent reduction of their degree of compaction in the bottom. As a
      consequence there is a lower TSS concentration in both return and waste flow,
      less biomass in the bioreactors and a reduction of the TSS removal efficiency.
      The control alternatives using a TSS controller substantially increase the food
      to microorganisms (F/M) ratio in the bioreactor, thereby reducing both risk and
      effects of bulking sludge. The effects of ammonium (NH(4)(+)), nitrate (NO(3)(-))
      and reject water control strategies are rather poor when it comes to handling
      solids separation problems.

PMID- 19844057
TI  - Microbial community associated with glucose-induced enhanced biological
      phosphorus removal.
AB  - The microbial community associated with enhanced biological phosphorus removal
      with glucose as the main carbon source at 11 degrees C was investigated using
      microscopy and molecular fingerprinting techniques. The study lasted 77 days and
      comprised two stages-Stage 1 when the mixture of glucose, yeast and dried milk
      was the organic carbon source and Stage 2 when glucose was the single carbon
      source. Rhodocyclus-related polyphosphate accumulating organisms, alpha
      Proteobacteria and Bacteroidetes constituted 42% in Stage 1 and 45% in Stage 2,
      21% in Stage 1 and 16% in Stage 2, and 10% in Stage 1 and 7% in Stage 2 of the
      total bacteria, respectively. The Trichococcus genus from the low GC Gram
      positive bacteria was possibly responsible for lactic acid production from
      glucose. The microbial community was gradually changing throughout the experiment
      and appeared to stabilize towards the end of the experiment. Periods of
      suboptimal phosphorus removal could have been caused by competition among
      different microbial communities for carbon substrate.

PMID- 19844058
TI  - Sustainable membrane operation design for the treatment of the synthetic coke
      wastewater in SMBR.
AB  - Membrane fouling in the membrane bioreactor (MBR) is typically caused by the
      interaction of microbial characteristics, hydrodynamic behavior, operation
      environment, wastewater characteristics and membrane properties, which result in
      the deterioration of performance and increasing energy consumption and cost of
      membrane replacement. The effect of the crucial MBR parameters (the microbial
      loading and characteristics, dissolved oxygen (DO), hydraulic retention time
      (HRT), backwashing conditions and membrane characteristics) on membrane fouling
      was investigated in a submerged membrane bioreactor (SMBR) during the long term
      treatment of synthetic coke wastewater. Also the optimum operation strategies
      were further utilized in order to satisfy the minimal membrane fouling operation
      through a long-term evaluation of the MBR performance. It has been demonstrated
      that with application of these optimal designed conditions, significant membrane
      fouling improvements were achieved over a long operating time, so it was possible
      to perform in sustainable operation for MBR. In this study, the upper limit of
      the sustainable flux is found to be as much as 18.6 L/m(2) h and the optimum
      sustainable flux value should be 50 approximately 75% of critical flux to satisfy
      the desired sustainable operation period.

PMID- 19844059
TI  - Optimal predictive control of water transport systems: Arret-Darre/Arros case
      study.
AB  - This paper proposes the use of predictive optimal control as a suitable
      methodology to manage efficiently transport water networks. The predictive
      optimal controller is implemented using MPC control techniques. The Arret
      Darre/Arros dam-river system located in the Southwest region of France is
      proposed as case study. A high-fidelity dynamic simulator based on the full Saint
      Venant equations and able to reproduce this system is developed in
      MATLAB/SIMULINK to validate the performance of the developed predictive optimal
      control system. The control objective in the Arret-Darre/Arros dam-river system
      is to guarantee an ecological flow rate at a control point downstream of the
      Arret-Darre dam by controlling the outflow of this dam in spite of the unmeasured
      disturbances introduced by rainfalls incomings and farmer withdrawals.

PMID- 19844060
TI  - Using runoff slope-break to determine dominate factors of runoff decline in Hutuo
      River Basin, North China.
AB  - Water resources in North China have declined sharply in recent years. Low runoff
      (especially in the mountain areas) has been identified as the main factor. Hutuo
      River Basin (HRB), a typical up-stream basin in North China with two
      subcatchments (Ye and Hutuo River Catchments), was investigated in this study.
      Mann-Kendall test was used to determine the general trend of precipitation and
      runoff for 1960-1999. Then Sequential Mann-Kendall test was used to establish
      runoff slope-break from which the beginning point of sharp decline in runoff was
      determined. Finally, regression analysis was done to illustrate runoff decline
      via comparison of precipitation-runoff correlation for the period prior to and
      after sharp runoff decline. This was further verified by analysis of rainy season
      peak runoff flows. The results are as follows: (1) annual runoff decline in the
      basin is significant while that of precipitation is insignificant at alpha=0.05
      confidence level; (2) sharp decline in runoff in Ye River Catchment (YRC)
      occurred in 1968 while that in Hutuo River Catchment (HRC) occurred in 1978; (3)
      based on the regression analysis, human activity has the highest impact on runoff
      decline in the basin. As runoff slope-breaks in both Catchments strongly
      coincided with increase in agricultural activity, agricultural water use is
      considered the dominate factor of runoff decline in the study area.

PMID- 19844061
TI  - Effect of feed characteristics on the organic matter, nitrogen and phosphorus
      removal in an activated sludge system treating piggery slurry.
AB  - Piggery wastewater is characterized by its high content in nitrogen and
      phosphorus, as well as by a low C/N ratio. This type of wastewater is
      traditionally spread to croplands (with its subsequent leaching to groundwater)
      or rarely discharged into natural water bodies, which ultimately cause severe
      episodes of eutrophication in aquatic ecosystems. In this context, activated
      sludge systems constitute a robust and efficient treatment option. The
      performance of an activated sludge process using a pre-denitrification
      configuration treating both sieved and flocculated swine slurry at a hydraulic
      retention time (HRT) of 7.7 days was evaluated. In order to avoid bacterial wash
      out, sludge from the settler was recirculated to the anoxic tank to accomplish
      denitrification. Once the biomass was acclimatized, the reactor was fed with
      swine slurry containing 19, 2.6, and 0.27 g/L of total chemical oxygen demand
      (COD), total Kjeldhal nitrogen (TKN), and soluble P, respectively. Nitrogen
      removal showed a clear dependency on the influent composition. When the influent
      TKN/total COD and soluble COD/total COD ratios were respectively 0.12-0.15 and
      0.7, the reactor exhibited good removal efficiencies (up to 99 and 91 for N
      NH(4)(+), TKN, respectively) while PO(4)(3-) was removed up to 65%. However, when
      the influent TKN/total COD ratio rose to 0.26 and soluble COD/total COD decreased
      to 0.3, the denitrification process was severely hindered concomitant with and
      accumulation of nitrite. Nevertheless, organic matter degradation was not
      affected by influent composition. At the last stage of the experiment, removals
      of dissolved phosphorus fell to 40% when the redox potential (ORP) profile showed
      a constant value of -400 mV, likely due to phosphate released from bacterial
      sludge.

PMID- 19844062
TI  - An empirical model for treatment of arsenic contaminated underground water by
      electrocoagulation process employing a bipolar cell configuration with continuous
      flow.
AB  - Arsenic (As) was removed electrochemically from underground water (GW) by
      electrocoagulation (EC) process employing a bipolar cell configuration with
      continuous flow using iron electrodes. A kinetic model derived from the Lagergren
      equation was applied to specify the kinetics of the arsenic removal reaction.
      Elucidation of the effect of the liquid flow rate on the treatment time and on
      the simulation results of the model was achieved. The results showed that
      treatment times decreased from 10.50 min to 0.75 min as the flow rate decreased
      from 3.500 to 0.875 L min(-1) and the current density varied from 15 to 45 A m(
      2) respectively. The used sorption kinetic model successfully describes the
      arsenic removal by this process. The coefficients of determination were found to
      be very high in all cases (R(2)>0.99) indicating a good fit of the experimental
      data to Lagergren model.

PMID- 19844063
TI  - The impact of groundwater quality on the removal of methyl tertiary-butyl ether
      (MTBE) using advanced oxidation technology.
AB  - In this study, the removal of methyl tertiary-butyl ether (MTBE) from
      contaminated groundwater using advanced oxidation technology was investigated.
      The UV/H(2)O(2) treatment process was applied to remove MTBE from two Saudi
      groundwater sources that have different quality characteristics with regard to
      their contents of inorganic species such as chloride, bromide, sulfates and
      alkalinity. MTBE was spiked into water samples collected from the two sources to
      a concentration level of about 250 microg/L. A 500 mL bench-scale forced-liquid
      circulation photoreactor was used to conduct the experiments. Two different UV
      lamps were utilized: 15 Watt low pressure (LP) and 150 Watt medium pressure (MP).
      Results of the study showed that the UV/H(2)O(2) process removed more than 90% of
      MTBE in 20 minutes when the MP lamp was used at an MTBE/H(2)O(2) molar ratio of
      1:200. The results also showed that groundwater sources with higher levels of
      radical scavengers such as alkalinity, bromide, nitrate and sulfate showed lower
      rate of MTBE removal.

PMID- 19844064
TI  - Development and evaluation of a reverse transcription-loop-mediated isothermal
      amplification assay for rapid and high-sensitive detection of Cryptosporidium in
      water samples.
AB  - We describe a novel assay for simple, rapid and high-sensitive detection of
      Cryptosporidium oocysts in water samples using a reverse transcription-loop
      mediated isothermal amplification (RT-LAMP). The assay is based on the detection
      of 18S rRNA specific for Cryptosporidium oocysts. The detection limit of the
      developed RT-LAMP assay was as low as 6 x 10(-3) oocysts/test tube, which
      theoretically enables us to detect a Cryptosporidium oocyst and perform
      duplicated tests even if water samples contain only one oocyst. The developed RT
      LAMP assay could more sensitively detect Cryptosporidium oocysts in real water
      samples than the conventional assay based on microscopic observation.

PMID- 19844065
TI  - Electrocoagulation efficiency of the tannery effluent treatment using aluminium
      electrodes.
AB  - An electro-coagulation laboratory scale system using aluminium plates electrodes
      was studied for the removal of organic and inorganic pollutants as a by-product
      from leather finishing industrial process. A fractional factorial 2(3)
      experimental design was applied in order to obtain optimal values of the system
      state variables. The electro-coagulation (EC) process efficiency was based on the
      chemical oxygen demand (COD), turbidity, total suspended solid, total fixed
      solid, total volatile solid, and chemical element concentration values. Analysis
      of variance (ANOVA) for final pH, total fixed solid (TFS), turbidity and Ca
      concentration have confirmed the predicted models by the experimental design
      within a 95% confidence level. The reactor working conditions close to real
      effluent pH (7.6) and electrolysis time in the range 30-45 min were enough to
      achieve the cost effective reduction factors of organic and inorganic pollutants'
      concentrations. An appreciable improvement in COD removal efficiency was obtained
      for electro-coagulation treatment. Finally, the technical-economical analysis
      results have clearly shown that the electro-coagulation method is very promising
      for industrial application.

PMID- 19844066
TI  - Design and study of a cost-effective solar photoreactor for pesticide removal
      from water.
AB  - In order to remove pesticides from water, a basic photoreactor has been built. We
      evaluated the performance of this photoreactor using two commercial
      photocatalytic materials from Ahlstrom group and from Saint-Gobain, with solar
      and artificial UV-lamps. We compared the kinetics of photocatalytic degradation
      and mineralization of Diuron in the same reactor with of both photocatalyst
      supports. We showed that Diuron is easily degraded under solar or artificial
      irradiation, while the kinetics of mineralization in the same condition are very
      slow. The behaviour of these commercial materials has been studied after several
      uses in the same conditions. We showed the effectiveness of this basic and cheap
      photoreactor for the elimination of pesticide in water.

PMID- 19844067
TI  - Kinetics of the sonophotocatalytic degradation of orange G in presence of Fe(3+).
AB  - The degradation and mineralization of orange G (OG) in aqueous solution by means
      of ultrasound irradiation at a frequency of 213 kHz and its combination with
      Fe(3+) were investigated. The effect of Fe(3+) concentration on the degradation
      efficiency was studied. The degradation of the dye followed first-order like
      kinetics under the conditions examined. A comparison study on the hybrid
      technique of sonophotocatalytic degradation in the presence of Fe(3+)
      (SonoFenton) with the individual techniques of photocatalysis and sonolysis was
      also performed. A slight synergistic enhancement in the degradation of the dye
      was observed during the sonophotocatalytic oxidation of OG using Fe(3+). The
      total organic carbon (TOC) measurements, carried out in order to evaluate the
      mineralization efficiency of OG using sonolysis, photocatalysis and
      sonophotocatalysis, showed a synergetic effect of combining sonolysis and
      photolysis.

PMID- 19844068
TI  - Investigation of liquid wax components of Egyptian jojoba seeds.
AB  - Egyptian jojoba seeds newly cultivated in Ismailia desert in Egypt promoted us to
      determine its lipid components. Fatty alcohols, fatty acids, wax esters and
      sterols patterns were determined by capillary GLC whereas, tocopherols profile,
      isopropenoid alcohols and sterylglycosides were determined by HPLC. The Egyptian
      seeds are rich in wax esters (55 %) with fatty alcohols C20:1 and C22:1 as major
      components and amounted to 43.0 % and 45.6 % respectively followed by C24:1 and
      C18:1(9.6 % and 1.3 % respectively). The fatty acids profile showed that C20:1 is
      the major constituent (60 %) followed by C18:1 and C22:1 (14.5 and 11.8 %
      respectively) whereas C24:1 was present at low concentration amounted to 1.6 %.
      In addition, the Egyptian jojoba wax contained C18:2 fatty acid at a level of 8.7
      %. Wax esters composition showed that the local wax had C42 and C40 esters as
      major components amounted to 51.1 and 30.1 % respectively. Also, it had C44 and
      C38 at reasonable amounts (10.0 and 6.3 % respectively). Whereas C36 and C46 were
      present at lower concentrations amounted to 1.4 and 1.1 respectively. The sterols
      analysis showed the presence of campe-, stigma-, beta-sito-, and isofuco- sterol
      amounting to 18.4 %, 6.9 %, 68.7 %, and 6.0 % respectively. The tocopherols
      pattern revealed that the local seed wax contained gamma-tocopherol as major
      constituent (79.2 %) followed by alpha-tocopherol (20.3 %). beta-tocopherol as
      well as delta-tocopherol were found as minor constituents. The isopropenoid
      alcohols and the sterylglycosides (free and acylated) were not detected. The wax
      is proposed to be used in oleo chemistry and cosmetics.

PMID- 19844069
TI  - High oleic enhancement of palm olein via enzymatic interesterification.
AB  - Acidolysis to incorporate oleic acid into refined, bleached and deodorized (RBD)
      palm olein (IV 56) using various lipases (enzymes) as catalysts to increase the
      oleic content of the oil was investigated. Immobilised lipases (lipase PLG,
      Lipozyme TL IM, Lipozyme RM IM and Novozym 435) and non-immobilised lipase
      (lipase PL) were used in this study to compare the effectiveness of the selected
      lipases in catalyzing the reaction to produce a high oleic oil. The results
      showed that the TAG of OLO/OOL content was increased at least 4 fold and OOO
      content was increased at least 3 fold when a 5% enzyme load was used. Lipase PL
      showed the greatest increase in tri-unsaturated triacylglycerols (TAGs) content.
      A pilot scale experiment conducted using TL IM enzyme, followed by recovery of
      the oil and fractionation allows the production of oils with varying oleic
      contents. A high oleic content of 56% was achievable.

PMID- 19844070
TI  - Micelle formation effect on electroacoustics in an aqueous surfactant solution:
      colloid vibration current and ion vibration current.
AB  - We measured the ultrasonic vibration current of aqueous solution of
      dodecyltrimethylammonium bromide (DTAB) and dodecyltrimethylammonium chloride
      (DTAC) as a function of surfactant concentration at 298.15 K under atmospheric
      pressure. The dependence of vibration current on the surfactant concentration
      exhibited a break point around the critical micelle concentration (CMC) in the
      DTAB system, whereas no break point was observed in the DTAC system. Taking
      account of the theory for vibration current, this suggests that the vibration
      current in the concentration regime higher than CMC depends on the electrostatic
      properties of micelle surface. From the difference in the slope of vibration
      current versus molarity curve above CMC, it was found that the zeta-potential of
      DTAC micelle is larger than that of DTAB micelle. This can be explained by the
      dissociation degree of counterions from the micelle surface. In addition, the
      theoretical equation of vibration current enabled us to estimate the partial
      molar volume of surfactant ions from the different behavior of vibration current
      in the concentration regime lower than CMC.

PMID- 19844071
TI  - Natural synergism of acid and lactone type mixed sophorolipids in interfacial
      activities and cytotoxicities.
AB  - Sophorolipids (SLs) naturally produced from Candida bombicola are a mixture of
      lactonic (SL-lactone) and acidic (SL-acid) sophorosides of 17-L-hydroxydecanoic
      acid with an SL-lactone:SL-acid ratio of 72:28. SLs are biodegradable low-foaming
      surfactants with high detergency and hardness-tolerance properties. To analyze
      the effect of the SL-lactone:SL-acid ratio on these properties, SL-LXs containing
      X% SL-lactone, in which X varied from 0 to 100, were prepared and their
      interfacial activities and cytotoxicities examined. The minimum surface tension
      values for all SLs examined were comparable. The critical micelle concentration
      (CMC) was 680 mg/L for SL-L0 and 62-110 mg/L for the other SLs. Interestingly,
      natural SL (SL-L72) had the lowest surface tension and CMC among all of the SLs
      examined. The foaming ability and stability of the SLs were dependent on the SL-L
      content. SL-L0 and L17 had higher foaming values than the other SLs examined in 0
      ppm hardness water. These values greatly reduced and became constant when the SL
      L content increased over 55%. The detergencies of all of the SLs examined were
      comparable, except for those of SL-L0 and SL-L100, which were slightly lower than
      those of the other SLs. These results suggest that natural synergism between SLs
      creates a better balance for many interfacial activities. The cytotoxicity of SL
      L72 was higher than that of SL-L0, but was comparable to that of surfactin, which
      is commercially available for cosmetic use. The low cytotoxicities and high
      interfacial properties of SLs increase their usefulness as biocompatible surface
      active agents for many applications.

PMID- 19844072
TI  - Protective effect of gemini surfactant on secondary structural change of bovine
      serum albumin in thermal denaturation up to 130 degrees C.
AB  - The effect of gemini surfactant, sodium dilauramidoglutamide lysine (DLGL), on
      the secondary structure of bovine serum albumin (BSA) was examined at 25 degrees
      C and at high temperatures up to 130 degrees C. The helicity (66%) of the protein
      decreased to 53% in the DLGL solution at 25 degrees C and it also decreased to
      16% with rise of temperature. Although approximately half of the original helical
      structures were destroyed upon heating up to 75 degrees C, most of the structures
      were maximally protected in the coexistence of 0.30 mM DLGL at 75 degrees C (the
      protein concentration was 0.010 mM). At temperatures below 75 degrees C, the
      protected helicity became maximal at such low DLGL concentrations. In the thermal
      denaturations above 80 degrees C, the protective effect did not appear at low
      DLGL concentrations, but monotonously enlarged with the surfactant concentration.
      On the other hand, upon cooling to 25 degrees C after the thermal denaturations
      below 75 degrees C, the helicity was maximally recovered to about 60% in the
      presence of DLGL below 0.30 mM. Upon cooling to 25 degrees C from high
      temperatures above 85 degrees C, the recovered helicity gradually increased with
      the surfactant concentration. The present novel effect, especially observed at
      low DLGL concentrations, might be fulfilled by the monomer ions of the gemini
      surfactant, since actual binding numbers of DLGL onto BSA are necessarily smaller
      than the mixing ratios around 30 mol/mol.

PMID- 19844074
TI  - Glycerol conversion to D-xylulose by a two-stage microbial reaction using Candida
      parapsilosis and Gluconobacter oxydans.
AB  - A yeast strain, 25N-2B, that produces D-arabitol from glycerol, was identified as
      Candida parapsilosis based on phylogenetic, morphological, physiological, and
      biochemical analyses. It produced 32.2 g/L D-arabitol from 170 g/L glycerol in a
      jar fermentor. The D-arabitol in the reaction mixture was then completely
      converted to D-xylulose using Gluconobacter oxydans NBRC3293. The product was
      isolated from the reaction mixture and confirmed to be D-xylulose by (1)H and
      (13)C-NMR and optical rotation.

PMID- 19844073
TI  - Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of
      limonoids from the seeds of Azadirachta indicia A. Juss. (neem).
AB  - Thirty-one nortriterpenoids, including 28 limonoids (1-28) and 3 degraded
      limonoids (29-31), and one diterpenoid (32), were isolated from the seed extract
      of Azadirachta indica (neem). Among these, six were new compounds and their
      structures were established to be 15-hydroxyazadiradione (3), 7-benzoyl-17
      hydroxynimbocinol (5), 23-deoxyazadironolide (12), limocin E (13), 23-epilimocin
      E (14), and 7alpha-acetoxy-3-oxoisocopala-1,13-dien-15-oic acid (32). Upon
      evaluation of compounds 1-32 on the melanogenesis in the B16 melanoma cells, five
      compounds, 20, 26, 27, 29, and 31, exhibited marked inhibitory effect (74-91%
      reduction of melanin content at 25 microg/mL) with no or almost no toxicity to
      the cells. Seven compounds, 1, 6, 9, 10, 18, 20, and 26, on evaluation for their
      inhibitory effect against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      inflammation (1 microg/ear) in mice, exhibited, except for compound 26, marked
      anti-inflammatory activity (ID(50) values 0.09-0.26 mg/ear). In addition, all of
      the 32 compounds exhibited moderate or potent inhibitory effects (IC(50) values
      of 230-501 mol ratio/32 pmol TPA) against the Epstein-Barr virus early antigen
      (EBV-EA) activation induced by TPA. Furthermore, on evaluation of azadirachtin B
      (21) for its anti-tumor-initiating activity on the two-stage carcinogenesis of
      mouse skin tumor induced by peroxynitrite (ONOO-; PN) as an initiator and TPA as
      a promoter, this exhibited marked inhibitory activity.

PMID- 19844075
TI  - Ecuador: public health genomics.
AB  - Ecuador has a heterogeneous population of almost 14 million people and a complex
      health care system provided through provincial and national health programs by
      government and private hospitals. There are public health facilities at regional
      and territorial level. Ecuador has a small cadre of genetic professionals that
      provide clinical genetic services in a few private medical centers in the main
      cities. Prenatal screening is offered exclusively in a few individual hospitals,
      with variable uptake as part of prenatal care. Surveillance of the effect of
      prenatal screening and diagnosis on the birth prevalence of congenital anomalies
      is limited by gaps and variations in surveillance systems. Newborn screening
      programs are almost inexistent. There is broad variation in optional
      participation in laboratory quality assurance schemes, and there are no
      regulatory frameworks that are directly pertinent to genetic testing services or
      population genetics. Health technology assessment in Ecuador is conducted by a
      diverse collection of organizations, several of which have produced reports
      related to genetics.

PMID- 19844076
TI  - Sequence variants in BMPR2 and genes involved in the serotonin and nitric oxide
      pathways in idiopathic pulmonary arterial hypertension and chronic thromboembolic
      pulmonary hypertension: relation to clinical parameters and comparison with left
      heart disease.
AB  - BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) and chronic
      thromboembolic pulmonary hypertension (CTEPH) share important pathogenic and
      clinical features. BMPR2 mutations are important in the pathogenesis of IPAH, but
      little is known about the genetic background in CTEPH. OBJECTIVE: To search for
      mutations and polymorphisms in genes involved in the BMPR2, serotonin and nitric
      oxide pathways possibly associated with pulmonary and cardiac disorders in IPAH
      and CTEPH. METHODS: In a cohort of Swiss patients with IPAH (n = 16) and CTEPH (n
      = 16), and in 24 controls with left heart disease without PH, polymorphisms in
      the BMPR2, 5-HHT, 5-HTR-2A and eNOS genes were analyzed and correlated with
      various clinical, functional and hemodynamic parameters. RESULTS: We found a
      BMPR2 missense mutation in a patient with coronary artery disease (CAD) without
      PH but no BMPR2 mutations in our collective with late-onset sporadic PH. In
      patients with polymorphic variants of the BMPR2 gene, the number of blood
      platelets and oxygen saturation were increased. The c.600A-->C synonymous variant
      was associated with worse exercise capacity and decreased quality of life in PH.
      We found no significant differences for any measured parameter according to the
      eNOS, 5-HTR2A and the 5-HTT polymorphisms, although there was a higher allelic
      frequency of the 5-HTT long variant in IPAH than in CTEPH and controls.
      CONCLUSION: Our first report of a BMPR2 mutation in a patient with CAD without PH
      is interesting and warrants further investigation. Our study may reflect the
      clinical status and genetic background in a typical PH cohort as seen in a single
      tertiary care referral center.

PMID- 19844077
TI  - Efficacy of a single educative intervention in patients with chronic plaque
      psoriasis.
AB  - BACKGROUND: An effective patient-physician relationship is important in the
      management of psoriatic patients. OBJECTIVE: Our purpose was to investigate the
      efficacy of an educational intervention for patients with psoriasis in improving
      disease knowledge and attitude towards physicians and systemic treatments.
      METHODS: The intervention consisted of a single, 2-hour educational programme
      conducted either by a dermatologist or by a dermatologist and a psychologist.
      Information on psoriasis and its treatment was given. A questionnaire concerning
      knowledge about psoriasis was administered before and after the programme, and
      after 6 months. RESULTS: 123 patients were enrolled. They reported a high degree
      of satisfaction with the intervention, improvement in knowledge about the disease
      and a better attitude towards therapy. After 6 months a better knowledge about
      the disease and a higher attitude to treatment were retained. CONCLUSIONS: A
      single educational intervention may be helpful in improving psoriasis knowledge
      and give psychological relief to patients.

PMID- 19844078
TI  - Prenatal diagnosis of androgen insensitivity syndrome.
AB  - Androgen insensitivity syndrome (AIS) (OMIM 300068) is an X-linked recessive
      genetic disorder with an XY karyotype that is caused by androgen receptor (AR)
      defects. We report a prenatal diagnosis case with clinical and molecular
      findings. The fetal phenotype was female, moreover the autopsy revealed the
      presence of abdominal testes confirmed by histopathological examination. The AR
      gene molecular analysis performed on the fetal DNA showed the presence of a
      c.2493C>T change in exon 4. The single nucleotide change resulted in a Q711X
      amino acid substitution within the AR ligand-binding domain of the protein that
      has never been described before in the literature. AIS is an important
      consideration in pregnancies that show sex discordance in ultrasonography and
      karyotype results with the opportunity to perform molecular analysis of the AR
      gene in order to confirm the diagnosis.

PMID- 19844079
TI  - Health and psychosocial complaints of elderly Ijaw widows in Yenagoa, Nigeria.
AB  - This study examined some health and psychosocial problems associated with
      mourning among 72 elderly Ijaw widows. The respondents complained of fever,
      gastrointestinal disorders and a range of psychosocial problems such as
      disinheritance, suspicion, frustration, hopelessness and degrading inhuman
      treatment. Community women/in-laws increased the extent to which elderly widows
      accepted traditional mourning rites. Care from nurses, good psychosocial support,
      health and conventional education enhanced the widows' health status and ability
      to cope with mourning rites. Elderly widows in polygamous marriages experienced
      better psychosocial support than those in monogamous marriages. Implications for
      nursing and psychological practices have been highlighted in this study.

PMID- 19844080
TI  - Reference values for 27 clinical chemistry tests in 70-year-old males and
      females.
AB  - BACKGROUND: Reference values are usually defined based on blood samples from
      healthy men or nonpregnant women in the age range of 20-50 years. These values
      are not optimal for elderly patients, as many biological markers change over time
      and adequate reference values are important for correct clinical decisions.
      OBJECTIVE: To validate NORIP (Nordic Reference Interval Project) reference values
      in a 70-year-old population. METHODS: We studied 27 frequently used laboratory
      tests. The 2.5th and 97.5th percentiles for these markers were calculated
      according to the recommendations of the International Federation of Clinical
      Chemistry on the statistical treatment of reference values. RESULTS: Reference
      values are reported for plasma alanine aminotransferase, albumin, alkaline
      phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate
      aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, creatine
      kinase, C-reactive protein, glucose, gamma-glutamyltransferase, HDL-cholesterol,
      iron, lactate dehydrogenase, LDL-cholesterol, magnesium, phosphate, potassium,
      sodium, transferrin, triglycerides, urate and urea. CONCLUSION: Reference values
      calculated from the whole population and a subpopulation without cardiovascular
      disease showed strong concordance. Several of the reference interval limits were
      outside the 90% CI of a Scandinavian population (NORIP).

PMID- 19844081
TI  - Blunted fasting-induced hypothalamic activation and refeeding hyperphagia in late
      onset obesity.
AB  - Hormonal and metabolic factors signal the status of energy balance to
      hypothalamic nuclei. Obesity is characterized by neuronal, metabolic and hormonal
      alterations. We therefore hypothesized that hypothalamic responses to challenges
      of energy balance may differ between lean and obese animals. To test this, we
      compared c-Fos expression in the hypothalamic arcuate (ARC) and paraventricular
      nuclei (PVN) and the lateral hypothalamic area (LHA) of mice (1-year-old) with
      late-onset obesity (LOO) and of lean controls under different feeding conditions.
      Fourteen hours of fasting induced high c-Fos expression in neuropeptide-Y
      positive ARC neurons, in the PVN and in the rostral LHA in lean but not in LOO
      mice. c-Fos expression in melanin-concentrating hormone (MCH) and orexin
      containing neurons in the caudal LHA was not affected by fasting. LOO mice showed
      fasting hyperinsulinemia, hyperleptinemia, elevated fasting blood glucose and an
      attenuated hyperphagic response during refeeding. Moreover, the anorectic
      response to leptin and hypoglycemic response to insulin were reduced in LOO mice.
      We conclude that adiposity blunts the neuronal responses to metabolic challenges
      in hypothalamic centers which control feeding behavior and energy balance.
      Elevated blood glucose may be one factor that suppresses hypothalamic
      responsiveness in obese mice. A similar impact of hyperinsulinemia and
      hyperleptinemia in LOO mice is also likely although under the current
      experimental conditions responsiveness to some effects of these hormones appeared
      to be reduced.

PMID- 19844082
TI  - Profiles of gonadal gene expression in the developing bovine embryo.
AB  - Our current understanding of the molecular basis of sex determination and gonadal
      development in humans is mostly an extrapolation of knowledge gained from studies
      in the mouse. However, the timing of gene expression in the mouse is unusual
      among mammals, and it is therefore important that data from other models are also
      available to help elucidate this pivotal process in human development. Here we
      describe the sequence of molecular and morphological events marking testis
      differentiation in bovine embryos. The genital ridges first appeared at CRL 12
      (day 32). SRY expression began at CRL 18 (day 37) and peaked at CRL 20 (day 39),
      leading to a cascade of regulatory, signaling, and steroidogenic gene expression
      at later stages, detected by quantitative real-time RT-PCR and
      immunohistochemistry. Testis cords were distinguishable at CRL 27 (day 42). We
      conclude that the timing of gene expression observed in developing human embryos
      is much more similar to bovine development than it is to the mouse. Therefore,
      Bos taurus may represent a useful model in which to study gene expression during
      sex determination, relevant to human development.

PMID- 19844083
TI  - It is 50 years since the discovery of the male determining role of the Y
      chromosome!

PMID- 19844084
TI  - Prevalence and cardiovascular features of Japanese hemodialysis patients with
      Fabry disease.
AB  - BACKGROUND: Fabry disease (FD) is a rare disease and one of the causes of
      progressive renal dysfunction. It results from an X-linked deficiency of alpha
      galactosidase A activity. It has been reported that its prevalence is much higher
      in hemodialysis patients than in the general population. However, its prevalence
      in Japanese hemodialysis patients and cardiovascular manifestations remain
      unclear. METHODS: We screened the alpha-galactosidase A activity of 1,024
      Japanese hemodialysis patients using a dried blood spot test. Patients with a low
      alpha-galactosidase A activity were assessed clinically, and a genetic study of
      the alpha-galactosidase A gene was performed for these patients. Furthermore,
      patients with FD underwent detailed cardiovascular examination. RESULTS: Forty
      six patients had low alpha-galactosidase A activity, and 1 man and 2 women had
      alpha-galactosidase A mutations (0.29%). All of these patients had a previously
      identified mutation (E66Q). The result of detailed cardiovascular examination
      showed that 2 patients had significantly impaired coronary flow reserve, reduced
      myocardial contraction and relaxation tissue Doppler velocities, and left
      ventricular hypertrophy. CONCLUSIONS: Measurement of the alpha-galactosidase A
      activity and the results of a genetic analysis indicated that the prevalence of
      FD in our hemodialysis patients was 0.29% (0.16% in men and 0.5% in women).
      Furthermore, comprehensive examination detected cardiovascular abnormalities in
      Japanese hemodialysis patients with FD.

PMID- 19844085
TI  - Circadian blood pressure classification scheme and the health of patients with
      chronic kidney disease.
AB  - BACKGROUND: In health, a sinusoidal rhythm is observed in systolic blood pressure
      (BP) that peaks (acrophase) during the waking hours (in-phase), but in those with
      chronic kidney disease (CKD) the acrophase is often observed during sleeping
      hours (out-of-phase). Yet in others the amplitude of the variation may be so
      blunted that acrophase may not be definable (phase-less). Circadian rhythms in
      systolic BP are often described by the dichotomous dipper classification but may
      not be adequate to fully characterize derangements in cyclical variation in BP.
      METHODS: To compare classification of circadian BP variation by phase-based
      classification to dipper-status we examined the cross-sectional relationship of
      these classification patterns to several markers of health such as health-related
      quality of life (Kidney Disease Quality of Life Survey, KDQOL) and physical
      activity (actigraphy over 2 weeks). We also assessed the relationship of
      circadian BP variation with circadian variation in urine electrolyte and albumin
      excretion rates. RESULTS: Among 103 veterans with CKD (97% men, age 69, diabetes
      mellitus 30%, eGFR 38.8 ml/min/1.73 m(2)) no differences were seen between
      dippers and non-dippers (n = 77, 75%) in eGFR, urinary Na and Cl excretion rates,
      or KDQOL. However, non-dippers had lower levels of physical activity and greater
      albuminuria compared to dippers. The same patients were classified to be in-phase
      (n = 36, 35%), phase-less (n = 19, 18%) or out-of-phase (n = 48, 47%). Patients
      in-phase had a higher eGFR and somewhat surprisingly also had the highest Na and
      Cl excretion rates compared to others. Those with out-of-phase systolic BP had
      the lowest physical composite score on KDQOL, the lowest level of physical
      activity, and the greatest amount of albuminuria. CONCLUSIONS: Among patients
      with CKD, circadian BP profile described by either dipper-based or phase-based
      classification is related to the level of physical activity and the severity of
      kidney damage. The circadian BP profile is related to overall health and
      nutritional intake only when using the phase-based classification. The value of
      these classification schemes to profile circadian BP will require longitudinal
      studies.

PMID- 19844086
TI  - Prognostic value of circadian blood pressure variation in chronic kidney disease.
AB  - BACKGROUND: Reduced circadian variation in blood pressure (BP) has been
      associated with cardiovascular morbidity, mortality and accelerated progression
      of kidney disease, but its independent prognostic value remains unknown. METHODS:
      Using 2 definitions, one based on dipping and the other based on BP pattern
      (assessed by cosinor rhythmometry), we studied the prognosis of circadian BP
      variation among 322 patients, 179 (56%) of whom had chronic kidney disease (CKD).
      RESULTS: During a follow-up period extending for up to 8.7 years, 116 (36%)
      patients died and 57 (32%) patients with CKD developed end-stage renal disease
      (ESRD). Compared to 106 patients (33%) who were dippers, the unadjusted hazard
      ratio (HR) for death among non-dippers was 2.03 (95% CI 1.30-3.16, p = 0.002).
      However, this HR became nonsignificant [1.39 (95% CI 0.89-2.19), p = 0.15] when
      adjusted for age and 24-hour average systolic BP. Although non-dipping was
      marginally associated with ESRD [HR 1.98 (95% CI 0.996-3.92), p = 0.051], even
      this association was weakened when adjusted for overall 24-hour systolic BP (HR
      1.67, p = 0.15). Similar to the dipping definition, the BP pattern-based
      definition was significantly associated with mortality (p = 0.005) but not with
      ESRD (p = 0.68). Compared to those 'in-phase,' the HR for death among those 'out
      of-phase' was 1.86 (95% CI 1.25-2.75, p = 0.002). Although this HR when adjusted
      for overall mean BP remained significant, when further adjusted for age, it too
      became nonsignificant. CONCLUSION: Among elderly veterans with or without CKD,
      circadian variation in BP is associated with mortality, but not ESRD. However,
      after accounting for common clinical risk factors, this association of circadian
      BP variation with mortality or ESRD is abolished.

PMID- 19844088
TI  - Polyunsaturated fatty acids, microflora and colitis.

PMID- 19844087
TI  - Sex and age result in differential regulation of the renal thiazide-sensitive
      NaCl cotransporter and the epithelial sodium channel in angiotensin II-infused
      mice.
AB  - BACKGROUND/AIMS: We determined the effects of age and sex on the blood pressure
      (BP) response to angiotensin II (Ang II) infusion and evaluated the potential
      mechanistic role of the thiazide-sensitive NaCl cotransporter (NCC) and the
      epithelial sodium channel (ENaC). METHODS: Male and female mice (approximately 3
      or 21 months of age) were infused with Ang II or control for 7 days. RESULTS:
      Males had a greater BP response to Ang II, somewhat enhanced by aging. Mean
      systolic BPs (at 7 days) were (mm Hg): 161, 143, 172, and 157 in young male,
      young female, old male, and old female mice, respectively. Immunoblotting changes
      in the whole kidney that supported this BP profile included a 51 and 52% increase
      in NCC band density in the old females and old males (as compared to sex
      respective controls) with Ang II infusion, while the young males and young
      females showed an increase of 40 and 0%, respectively. Young males also had a
      greater reduction in major bands of beta- and gamma-ENaC, than did young female
      mice. The natriuretic response to hydrochlorothiazide supported an increase in
      activity of NCC with Ang II in aged mice only. CONCLUSIONS: Increased sensitivity
      to Ang II in aging and male mice may involve overactivity of NCC.

PMID- 19844090
TI  - The effect of Bifidobacterium lactis on the growth of infants: a pooled analysis
      of randomized controlled studies.
AB  - BACKGROUND/AIMS: Breast milk is the best source of nutrition for the growth of
      the newborn infant. It is therefore essential that mothers who cannot breastfeed
      or choose not to are provided with alternatives that closely match the
      composition and functionality of breast milk. This study aimed to investigate the
      growth effects of probiotic-supplemented formulas on both healthy and vulnerable
      populations of infants. METHODS: A meta-analysis of data from 5 randomized
      controlled clinical trials that included infants fed formulas containing a
      probiotic Bifidobacterium lactis CNCM I-3446 was performed (n = 525). A sub
      analysis was performed among infants of HIV-positive mothers (n = 120). Growth
      measurements (gain in weight and body mass index, BMI, from enrollment to 120
      days) were compared between infants fed a formula containing B. lactis and those
      fed a control formula. Changes in length and Z-scores were also compared.
      RESULTS: Formula with B.lactis was demonstrated to be at least as good as formula
      without B. lactis in the meta-analysis of 5 studies. The lower boundary of the
      95% confidence interval (CI) of the differences in mean weight gain (95% CI 0.09
      2.93 g/day) was above the predefined non-inferiority margin of -3.0 g/day.
      Moreover, among infants with HIV-positive mothers, weight gain of those taking B.
      lactis was significantly higher than of those not taking B. lactis, by 3.1 g/day
      (95% CI 0.4-5.8 g/day, p = 0.0226) and the BMI gains were significantly higher,
      by 6.4 g/m(2)/day (95% CI 0.0.3-12.5 g/m(2)/day, p = 0.0400). The corresponding
      weight for age and BMI Z-scores were also significantly higher, by 0.37 (95% CI
      0.03-0.71, p = 0.0308) and by 0.42 (95% CI 0.02-0.83, p = 0.0377), respectively,
      whereas differences in length gain or length-for-age Z-score were not
      significant. Among infants in the non-HIV mothers group, there were no
      significant differences between infants fed formulas with or without B. lactis,
      for any of the growth parameters. CONCLUSIONS: The analysis suggests that B.
      lactis may have a positive effect on growth in vulnerable populations,
      specifically in infants born to mothers with HIV.

PMID- 19844092
TI  - Simultaneous ring voice-over-Internet phone system enables rapid physician
      elicitation of explicit informed consent in prehospital stroke treatment trials.
AB  - BACKGROUND: Cellular phone conversations between on-scene patients or their
      legally authorized representatives (LARs) and off-scene enrolling physician
      investigators require immediate and reliable connection systems to obtain
      explicit informed research consent in prehospital treatment trials. METHODS: The
      NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial implemented
      a voice-over-internet protocol (VOIP) simultaneous ring system (multiple
      investigator cell phones called simultaneously and first responder connected to
      call) to enable physician-investigators to elicit consent immediately from
      competent patients or LARs encountered by 228 ambulances enrolling patients in a
      multicenter prehospital stroke trial. For 1 month, the number, origin, duration,
      and yield of enrolling line calls were monitored prospectively. RESULTS: Six
      investigators were connected to 106 enrolling line calls, with no identified
      unanswered calls. Thirty-five percent of new patient calls yielded an enrollment.
      The most common reasons for non-enrollment were last known well >2 h (n = 7) and
      unconsentable patient without LAR available (n = 7). No non-enrollments were
      directly attributable to the VOIP system. In enrollments, consent was provided by
      the patient in 67% and a LAR in 33%. The duration of enrollment calls (mean +/-
      SD: 8.4 +/- 2.5 min, range 6-14) was longer than non-enrollment calls (5.5 +/-
      3.5, range 2-13; p < 0.001). The median interval from last known well to study
      agent start was 46 min, and 70% were enrolled within 60 min of onset.
      CONCLUSIONS: The simultaneous ring system was reliable and effective, permitting
      enrollment of a substantial number of patients within the first hour after stroke
      onset. VOIP cellular networks with simultaneous ring are a preferred means of
      facilitating consent in prehospital treatment trials.

PMID- 19844089
TI  - Exercise training and dietary glycemic load may have synergistic effects on
      insulin resistance in older obese adults.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the combined effects of
      exercise and dietary glycemic load on insulin resistance in older obese adults.
      METHODS: Eleven men and women (62 +/- 2 years; 97.6 +/- 4.8 kg; body mass index
      33.2 +/- 2.0) participated in a 12-week supervised exercise program, 5 days/week,
      for about 1 h/day, at 80-85% of maximum heart rate. Dietary glycemic load was
      calculated from dietary intake records. Insulin resistance was determined using
      the euglycemic (5.0 mM) hyperinsulinemic (40 mU/m(2)/min) clamp. RESULTS: The
      intervention improved insulin sensitivity (2.37 +/- 0.37 to 3.28 +/- 0.52
      mg/kg/min, p < 0.004), increased VO(2max) (p < 0.009), and decreased body weight
      (p < 0.009). Despite similar caloric intakes (1,816 +/- 128 vs. 1,610 +/- 100
      kcal/day), dietary glycemic load trended towards a decrease during the study (140
      +/- 10 g before, vs. 115 +/- 8 g during, p < 0.04). The change in insulin
      sensitivity correlated with the change in glycemic load (r = 0.84, p < 0.009).
      Four subjects reduced their glycemic load by 61 +/- 8%, and had significantly
      greater increases in insulin sensitivity (78 +/- 11 vs. 23 +/- 8%, p < 0.003),
      and decreases in body weight (p < 0.004) and plasma triglycerides (p < 0.04)
      compared to the rest of the group. CONCLUSION: The data suggest that combining a
      low-glycemic diet with exercise may provide an alternative and more effective
      treatment for insulin resistance in older obese adults.

PMID- 19844093
TI  - Relationship between high-sensitivity C-reactive protein and clinical functional
      outcome after acute ischemic stroke in a Korean population.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) has been shown to be a
      powerful predictor of coronary ischemic events. However, the prognosis of
      functional disability in patients with cerebrovascular disease has not been well
      established. Therefore, we performed this study to determine the prognostic
      significance of hs-CRP levels in patients with functional disability after acute
      ischemic stroke. METHODS: A total of 417 Korean patients with ischemic stroke
      were examined within 24 h after symptom onset. hs-CRP measurements were obtained
      on admission and on the seventh hospital day. The correlations between the
      concentration of hs-CRP and functional disability duration 12 months after stroke
      onset were analyzed. RESULTS: The present study showed that hs-CRP levels on
      admission and on the seventh hospital day were significantly correlated with the
      modified Rankin Scale (mRS) score 12 months after stroke onset. These results
      also demonstrated that mRS scores are more closely associated with hs-CRP levels
      on the seventh hospital day than hs-CRP levels on admission. CONCLUSION: This
      study demonstrated that elevated hs-CRP levels on the seventh hospital day,
      rather than within 24 h after stroke onset, could strongly predict the prognosis
      of functional disability. These results supported that hs-CRP is a useful marker
      of ischemic stroke in the Korean population.

PMID- 19844094
TI  - Post-stroke depressive symptoms are associated with post-stroke characteristics.
AB  - BACKGROUND: Several studies have described the frequency and risk factors of post
      stroke depressive symptoms (PSDS). However, most studies did not exclude patients
      with depressive symptoms shortly before stroke and paid little attention to
      prestroke risk factors of depression, including previous depressive episodes,
      white matter lesions, and brain atrophy. These are potential limitations to
      assess the true effect of stroke on the occurrence of depressive symptoms. Our
      aim was to investigate the prevalence and risk factors of PSDS with adjustments
      for the previously mentioned prestroke factors. METHODS: 420 consecutive patients
      with an acute clinical symptomatic transient ischemic attack or cerebral
      infarction were eligible for enrolment in this study. The presence of PSDS was
      rated by the Hospital Anxiety and Depression Scale 6-8 weeks after stroke. The
      relation between (pre-) stroke factors and PSDS was assessed with multivariate
      regression analysis. RESULTS: The prevalence of PSDS was 13% and did not differ
      between stroke subtype or first-ever/ever occurrence of stroke. Higher degree of
      post-stroke handicap was related to PSDS (OR = 5.39; 95% CI = 2.40-12.08) and
      more functional independence had a protective effect on PSDS (OR = 0.88; 95% CI =
      0.77-1.00). CONCLUSIONS: This is the largest study that investigated the
      prevalence and risk factors of PSDS by carefully excluding patients with
      depressive symptoms shortly before stroke. PSDS were not related to lesion side
      or location, but to the degree of post-stroke handicap and functional
      independence. Early detection of PSDS and their risk factors might help to
      predict long-term outcome and could promote early interventions of (behavioral)
      rehabilitation treatment strategies.

PMID- 19844095
TI  - TIMP-2 gene polymorphism is associated with intracerebral hemorrhage.
AB  - BACKGROUND: Both ischemic stroke and intracerebral hemorrhage are associated with
      altered expression and activation of matrix metalloproteinases (MMPs).
      Particularly relevant are MMP-2 and MMP-9. This proteolytic effect is dampened by
      tissue inhibitors of metalloproteinases (TIMPs). TIMP-2 is an important
      endogenous inhibitor of MMP-2. Alterations in the TIMP-2 gene expression may
      contribute to the incidence of ischemic stroke and intracerebral hemorrhage.
      METHODS: TIMP-2 gene SNP -261G/A was genotyped from sequentially recruited stroke
      patients (n = 356, f/m 151/205, mean age 68.2 years, range 19-100 years) and
      gender and age matched controls (n = 253, f/m 114/139, mean age 68.5 years, range
      32-92 years). The SNP -261G/A was detected after gene sequencing of 95 patients
      and controls. Furthermore, in a subgroup of 93 patients the serum levels of TIMP
      2 were measured during the first 7 days after stroke onset and compared to the
      genotype. RESULTS: SNP -261G/A in the TIMP-2 gene shows an allele frequency of
      approximately 39.14%. Homozygosity for allele A is associated significantly with
      the development of ICH (p = 0.025, OR = 2.020, CI = 1.115-3.661) as compared to
      heterozygosity and homozygosity for allele G (recessive genotypic model).
      Concordantly, the serum levels of TIMP-2 showed a nonsignificant decreases,
      depending on the genotype (p = 0.111). CONCLUSION: We investigated a SNP 261 base
      pairs upstream of the start codon in exon 1 of TIMP-2. Our data suggest that
      carriers of homozygosity for allele A are at increased risk of developing
      intracerebral hemorrhage.

PMID- 19844096
TI  - Gender differences in mortality after hospital admission for stroke.
AB  - BACKGROUND: Differences between men and women in stroke symptoms, management and
      disability have been reported to be unfavorable for women. Yet, studies into
      differences between men and women in survival after a stroke yielded inconsistent
      results. We investigated whether gender was associated with all-cause mortality
      after hospital admission for stroke. METHODS: A nationwide cohort of patients
      with a first admission for stroke and stroke subtypes was identified through
      linkage of national registers. Age- and gender-specific mortality risks were
      quantified for 28-day case-fatality, 1-year and 5-year periods. Cox regression
      models were used to adjust for potential confounding factors. RESULTS: We
      identified 30,675 stroke patients (15,925 women, 14,750 men). In ischemic-stroke
      patients, 28-day case-fatality, 1-year and 5-year mortality risk (hazard ratio
      (HR) 0.90; 95% confidence interval (CI) 0.85 to 0.95, HR 0.88; 95% CI 0.84 to
      0.92, HR 0.84; 95% CI 0.81 to 0.88, respectively) and in intracerebral-hemorrhage
      patients, 1-year and 5-year mortality risks (HR 0.92; 95% CI 0.86 to 0.99) were
      lower for women compared to men after adjustment for age and previous admissions
      for cardiovascular diseases or diabetes mellitus. In subarachnoid hemorrhage
      patients, no differences between men and women in crude and adjusted mortality
      risks were observed. When all stroke types were combined, differences in
      mortality risk between men and women were seen, and appeared to differ by age
      (increased risk in young women, lower risk in older women). CONCLUSIONS: Women
      have lower 28-day case-fatality and long-term mortality risks after an ischemic
      stroke and lower 1-year and 5-year mortality risks after an intracerebral
      hemorrhage compared to men, whereas no differences in mortality risks were found
      for subarachnoid hemorrhage.

PMID- 19844097
TI  - Safety and efficacy of IV-TPA for ischaemic stroke in clinical practice--a
      Bayesian analysis.
AB  - BACKGROUND: Observational studies of new treatments in routine practice are
      clinically important but may be limited by bias. We used a Bayesian approach to
      interpret and sequentially combine phase 4 studies of IV-TPA within 3 h for acute
      ischaemic stroke to quantify the cumulative evidence for the efficacy and safety
      of this therapy in clinical practice. METHODS: Prior probability distributions
      for favourable outcome (modified Rankin Score, mRS, 0-1), symptomatic
      intracerebral haemorrhage, and mortality 3 months after IV-TPA were derived from
      the NINDS trial. Phase 4 studies from observational case series and from
      regulator-mandated large registries were included. A cumulative analysis was
      performed to quantify the increase in the total evidence base over time,
      unadjusted and adjusted for potential bias. RESULTS: The cumulative analysis
      indicated that IV-TPA <3 h was associated with 3-month favourable outcome in
      37.1% (95% credible interval, CrI, 36.1-38.0%, n = 9,578) compared to 26% (95%
      confidence interval, CI, 19.6-32.9%, n = 165) in placebo-treated patients in
      NINDS, symptomatic intracranial haemorrhage in 6.6% (95% CrI 5.9-7.4%, n = 10,
      834) compared to 6.4% (95% CI 4.0-9.4%) in the NINDS IV-TPA group, and 3-month
      mortality in 13.6% (95% CrI 12.6-14.8%, n = 9, 901) compared to 20.5% (95% CI
      16.0-25.0%, n = 312) in the NINDS placebo group. CONCLUSION: A Bayesian approach
      provides further confirmatory evidence of the efficacy and safety of IV-TPA for
      treatment of acute ischaemic stroke within 3 h in diverse clinical practice
      settings, after adjusting for potential observational bias.

PMID- 19844098
TI  - Indices of kidney dysfunction and discharge outcomes in hospitalized stroke
      patients without known renal disease.
AB  - BACKGROUND: The utility of clinical measurements of impairments in glomerular
      barrier or filtration rate among hospitalized stroke patients without known
      chronic kidney disease (CKD) has not been well studied. We determined whether
      various indices of CKD would predict discharge outcomes in persons hospitalized
      with a recent ischemic stroke. METHODS: Presence of proteinuria and estimated low
      glomerular filtration rate (GFR) <60 ml/min per 1.73 m(2) on admission were
      assessed in consecutive ischemic stroke and transient ischemic attack patients
      admitted to a university hospital over 18 months, who had no history of CKD. The
      primary discharge outcomes assessed (among stroke patients only) were death or
      disability (modified Rankin Scale score > or =2) and being discharged home
      directly from hospital. Independent effects of CKD indices on the outcomes were
      evaluated using multivariable regression modeling. RESULTS: Of 251 patients with
      recent ischemic cerebrovascular events, 198 ischemic stroke patients (79%), met
      the study criteria. In crude analyses, persons with proteinuria or low GFR were
      significantly more likely to die in the hospital (p < 0.05). After adjusting for
      confounders, proteinuria was independently linked with lower odds of going home
      directly from the hospital (OR = 0.38, 95% CI = 0.16-0.92) and poorer discharge
      functional status (OR = 3.19, 95% CI = 1.37-7.46), but low GFR was not
      independently related to either of these outcomes. CONCLUSIONS: Among
      hospitalized ischemic stroke patients without known CKD, presence of proteinuria
      on admission is independently associated with poorer discharge functional
      activity and lower likelihood of being discharged home directly. Low GFR was not
      related to either outcome in these patients without known CKD.

PMID- 19844099
TI  - Hemostatic factors and subclinical brain infarction in a community-based sample:
      the ARIC study.
AB  - BACKGROUND: Previous data are conflicting as to whether imbalance between
      hemostatic factors is associated with clinical strokes. We evaluated the
      association between hemostatic factor levels and subclinical lacunar infarcts in
      a nested sample from a subset of the Atherosclerosis Risk in Communities (ARIC)
      cohort. METHODS: 196 cases without clinical strokes had lacunar infarcts by MRI,
      and 214 controls without radiographic infarcts were frequency-matched by age
      group and sex. Logistic regression models were fitted to assess the association
      between levels of hemostatic markers and case status. RESULTS: In age-, race- and
      sex-adjusted models, von Willebrand factor (vWF) and D-dimer were positively
      associated with case status, with odds ratios for the highest vs. lowest tertile
      of 2.0 (95% CI 1.2-3.6) for vWF and 1.76 (95% CI 1.02-3.0) for D-dimer.
      Plasminogen had nonsignificant inverse associations with presence of silent
      lacunar infarcts. CONCLUSIONS: vWF and D-dimer were positively associated, and
      plasminogen was nonsignificantly inversely associated with subclinical
      radiographic infarct. Further studies on the role of these hemostatic factors in
      the development of silent lacunar infarcts may help elucidate the mechanisms
      behind this injury and may even point to potential targets for future
      intervention.

PMID- 19844100
TI  - Safety of eptifibatide for subcortical stroke progression.
AB  - BACKGROUND: There is no proven treatment for stroke progression in patients with
      subcortical infarcts. Eptifibatide, a glycoprotein IIb/IIIa inhibitor, might halt
      stroke progression by improving flow in the microcirculation. METHODS: We
      conducted a retrospective analysis of patients with subcortical stroke who
      experienced deterioration and were treated with eptifibatide (loading dose 180
      microg/kg; infusion 2 m microg/kg/min) for 24-48 h. Oral antiplatelet agents were
      started 6 h before discontinuation of eptifibatide. RESULTS: Twenty-four patients
      with subcortical strokes were treated. The median admission NIHSS score was 5.0,
      which worsened to 8.5 (motor 5.0) before starting eptifibatide. The median NIHSS
      score 24 h after starting eptifibatide was 5.5. At 24 h, 42% had motor NIHSS
      scores less than or equal to pre-deterioration scores (50% for total NIHSS), and
      50% had improved at least 1 motor point compared to pre-eptifibatide scores,
      which was sustained until hospital discharge. At discharge, the median total
      NIHSS score was 4.5. Ninety-two percent of patients were discharged home or to
      inpatient rehabilitation. Treatment was stopped early in 1 case due to a platelet
      drop <100,000/microl. No systemic or intracerebral bleeding occurred.
      CONCLUSIONS: Eptifibatide infusion may be safe in patients with subcortical
      ischemic strokes. Future studies are needed to test the safety and potential
      efficacy of this agent in subcortical stroke progression.

PMID- 19844101
TI  - Multiple biological predictors for vulnerable carotid lesions.
AB  - BACKGROUND: In this study a multiscore analysis of various biomarkers including
      matrix metalloproteinases (MMPs), inflammatory factors and other clinical
      parameters was performed to establish a set of reliable biomarkers for improved
      detection of plaque instability in patients with advanced carotid stenosis.
      METHODS: Study patients (n = 101) were classified as histologically stable (n =
      37) or unstable (n = 64). Serum levels of MMP-1, -2, -3, -7, -8, -9, MMP
      inhibitors TIMP-1, -2, and inflammatory factors such as tumor necrosis factor
      (TNF-alpha), interleukin (IL)-1beta, -6, -8, -10, and -12 were measured by ELISA
      assays. Multiscore analysis was performed using multiple receiver operating
      characteristics analysis and determination of appropriate cutoff values. RESULTS:
      Circulating levels of MMP-1, -7, TIMP-1, TNF-alpha, and IL-8 were significantly
      enhanced in patients with unstable plaques compared to individuals with stable
      lesions, mean differences being 1.2 (p = 0.032), 2.5 (p = 0.004), 30.0 (p =
      0.014), 1.3 (p = 0.047), and 2.2 (p = 0.033), respectively. The combination of
      MMP-1, -7, TIMP-1 and IL-8 demonstrated the highest positive predictive value of
      89.4% and negative predictive value of 60.1% for patients correctly classified as
      individuals with unstable and stable carotid lesions by means of blood sample
      analysis. CONCLUSIONS: Multiple relevant biomarkers that play a decisive role in
      plaque instability can improve the correct determination of vulnerable carotid
      plaques in patients with advanced carotid artery stenosis.

PMID- 19844102
TI  - Physician-determined worsening heart failure: a novel definition for early
      worsening heart failure in patients hospitalized for acute heart failure-
      association with signs and symptoms, hospitalization duration, and 60-day
      outcomes.
AB  - OBJECTIVES: To evaluate physician-determined worsening heart failure (PD-WHF) in
      patients admitted with acute heart failure (AHF). METHODS: The PROTECT pilot
      study evaluated rolofylline, an adenosine A(1) receptor antagonist, versus
      placebo in patients with AHF and renal impairment. Signs and symptoms of heart
      failure (HF) and diuretic administration were prospectively recorded daily for 7
      days and patients were followed for 60 days. Patients were categorized into three
      groups: (A) PD-WHF, based on worsening symptoms and signs of HF and need for
      additional intravenous (IV) or mechanical therapy (n = 29); (B) increased IV
      diuretic therapy without PD-WHF (n = 61), and (C) neither PD-WHF nor increase in
      IV diuretic dose (n = 211). RESULTS: Patients in group A had slower resolution of
      dyspnea, longer mean (+/-SD) length of hospitalization (13.8 +/- 6.8 vs. 10.5 +/-
      8.5 and 9.3 +/- 5.9 days in groups B and C, respectively; p < 0.05 for both), and
      higher 60-day death and cardiovascular or renal readmission rates [49.7 (95%
      confidence interval: 33.1-69.1) vs. 37.3 (26.4-50.9) vs. 19.5% (14.7-25.6) in
      groups B and C, respectively]. PD-WHF was a strong independent predictor of
      length of stay and 60-day death and cardiovascular or renal readmission.
      CONCLUSIONS: PD-WHF may be an indicator of short-term risk and treatment efficacy
      in AHF.

PMID- 19844103
TI  - Cardiac arrhythmias in multiple organ dysfunction syndrome: a mechanistic
      approach.

PMID- 19844104
TI  - Investigation of the alterations in cellular electrophysiology underlying
      ventricular arrhythmia in dogs with the multiple organ dysfunction syndrome.
AB  - BACKGROUND: Multiple organ dysfunction syndrome (MODS)-specific cellular
      electrophysiological changes have so far not been reported and it seemed unlikely
      that they were related to arrhythmogenesis. METHODS AND RESULTS: Twelve dogs,
      weight 12 +/- 2 kg, were divided into a control group (n = 6) and an MODS group
      (n = 6). MODS lasting for 72 h was induced by the 'two-hit' method in 6 dogs.
      Ventricular myocytes were enzymatically isolated. Early afterdepolarizations
      (EADs), action potential duration (APD) and L-type calcium currents (ICa,L) were
      assessed. Sinus arrhythmias in all MODS dogs (100%; 6 of 6) and premature
      ventricular beats in 4 MODS dogs (66%; 4 of 6) were recorded, while no
      arrhythmias were found in the control animals. The prolongation of the APD was
      associated with a decreased ICa,L, and frequently provoked EADs were the typical
      electrophysiological alterations in the myocytes of MODS dogs. The action
      potential prolongation was shortened, the ICa,L blocked and EAD suppressed by
      using verapamil (100 micromol/l) in the myocytes of MODS dogs (66%; 4 of 6).
      CONCLUSION: The changes in cellular electrophysiology within 72 h in the heart of
      MODS dogs are APD prolongation, markedly decreased ICa,L as well as frequently
      provoked EAD, the most common types of arrhythmia being sinus arrhythmia and
      premature ventricular beats. This study suggests that verapamil appears to be an
      effective agent in reversing alterations in cellular electrophysiology at the
      early stage of MODS.

PMID- 19844105
TI  - Cerebrospinal fluid total tau is associated with shorter survival in dementia
      with Lewy bodies.
AB  - A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to
      increase mortality to a greater extent than the pathology of Alzheimer's disease
      (AD). However, mortality in DLB has also been shown to increase with concomitant
      AD pathology. Furthermore, in a recent publication, we showed that there is a
      robust and specific increase in CSF calcium and magnesium in DLB patients
      compared to both AD patients and controls. Thus, in order to explore the
      influence of CSF AD markers and trace element concentrations on mortality in DLB,
      we undertook a longitudinal prospective study of 47 clinically diagnosed DLB
      patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB
      patients showed an increased mortality compared to the healthy controls (relative
      risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were
      associated with increased mortality among the DLB patients (p < 0.05), but not
      among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration
      and phosphorylated tau, and CSF trace element concentrations did not influence
      survival in the obtained models.

PMID- 19844106
TI  - High systolic and pulse pressure levels are associated with better cognitive
      performance in patients with probable Alzheimer's disease: a cross-sectional
      observational study in a geriatric outpatient population.
AB  - BACKGROUND: The prevalence of cardiovascular disease and Alzheimer's disease (AD)
      increases with age. A number of studies have demonstrated an association between
      AD and cardiovascular risk factors and disease. However, data are inconsistent.
      METHODS: Cross-sectional observational study in a geriatric outpatient
      population. Analysis of data from 327 patients diagnosed with probable AD in a
      geriatric outpatient clinic. Comparison of blood pressure levels, cardiovascular
      diagnoses, and Mini-Mental State Examination (MMSE) score between the patients.
      RESULTS: MMSE score decreased with age (beta = -0.25; 95% CI: -0.35 to 0.15), and
      a positive correlation was found with systolic blood pressure (beta = 0.03; 95%
      CI: 0.003-0.06), pulse pressure (beta = 0.05; 95% CI: 0.01-0.08) and hypertension
      (beta = 1.56; 95% CI: 0.05-3.07). An increase in cardiovascular disease load had
      a negative effect on cognitive performance. After adjustment for duration of
      dementia (data present for 216 patients), results were slightly changed.
      CONCLUSIONS: Higher systolic blood pressure and pulse pressure were associated
      with a better cognitive test performance. Patients with probable AD and 2 or more
      cardiovascular diagnoses had lower MMSE scores.

PMID- 19844107
TI  - Management of reflux symptoms with over-the-counter proton pump inhibitors:
      issues and proposed guidelines.
AB  - BACKGROUND: Symptoms of gastroesophageal reflux are widely prevalent. There is a
      continuum between subjects with mild reflux symptoms and those severely affected
      by gastroesophageal reflux disease (GERD). Both groups may at times access over
      the-counter (OTC) therapies. For the purpose of this review, relevant papers,
      including national and international guidelines were reviewed and recommendations
      made for appropriate use of OTC proton pump inhibitor (PPI) therapy. RESULTS:
      PPIs are the gold standard for treatment of reflux symptoms. OTC therapy with
      histamine(2) receptor antagonists (H2RAs) also plays a role. For the majority
      affected by reflux symptoms, effective symptom control is the most important
      outcome, as only a subgroup requires investigations or interventions. However,
      patients with alarm features (i.e. troublesome dysphagia, weight loss,
      predominant upper abdominal pain) are not recommended for OTC therapy and need
      prompt medical referral. Frequent relapses or failure to adequately respond to
      OTC therapy are additional triggers for medical assessment. CONCLUSIONS: OTC
      treatment of typical reflux symptoms (acid regurgitation, heartburn) with
      antacids and H2RAs is now accepted as safe and results in short-term relief of
      symptoms. There is no evidence of additional risk with OTC PPIs compared to these
      existing OTC therapies and PPIs are significantly more efficacious.

PMID- 19844109
TI  - Use of coagulant spray glue (Glubran 2) for aerostatic purposes in pulmonary
      parenchyma resections in pigs: a preliminary study.
AB  - BACKGROUND: The aim of our study was to test the aerostatic validity of a cyan
      acrylic glue (Glubran 2), applied by means of a spray catheter, on an
      experimental pig model. MATERIALS AND METHODS: 15 young pigs were divided into
      three study groups of 5 based on surgical techniques: (1) atypical pulmonary
      resection with mechanical suturing and reinforcement with continuous suturing;
      (2) resection of the pulmonary parenchyma with a cold scalpel, followed by local
      application of Glubran 2; (3) atypical pulmonary resection with mechanical
      suturing followed by application of Glubran 2. RESULTS: The mean aerostasis time
      was calculated at 3.5 +/- 1.26 s. The histopathological analysis did not show any
      particular differences when comparing the effects of the treatments carried out
      with Glubran 2 spray glue and the standard treatments. No statistically
      significant differences were recorded in the short- and medium-term survival of
      pigs treated with Glubran 2 compared with the respective control groups.
      CONCLUSIONS: The application of Glubran 2 spray on wounds caused by pulmonary
      resections in pigs proved to have a rapid and effective influence for the
      purposes of aerostasis without significant differences in air losses and
      survivals.

PMID- 19844108
TI  - Geranylgeranylacetone protects against diclofenac-induced gastric and small
      intestinal mucosal injuries in healthy subjects: a prospective randomized placebo
      controlled double-blind cross-over study.
AB  - BACKGROUND AND AIMS: Little information is available regarding the prevention and
      treatment of small intestinal mucosal injuries caused by non-steroidal anti
      inflammatory drugs (NSAIDs). We planned a pilot study to investigate the
      protective effects of geranylgeranylacetone (GGA) against NSAID-induced small
      intestinal injuries using video capsule endoscopy (VCE). SUBJECTS AND METHODS:
      Ten healthy male volunteers took oral GGA 300 mg/day (regimen A) or placebo
      (regimen B) in addition to diclofenac 75 mg/day + rabeprazole 20 mg/day for 7
      days. We conducted a cross-over trial of regimens A and B with a 2-week washout
      period. All subjects underwent VCE before and after each administration period,
      and were evaluated for NSAID-induced gastric and small intestinal mucosal
      lesions. RESULTS: The number of mucosal lesions (erosions, ulcers and a red spot
      with possible bleeding) detected in both stomach and small bowel changed between
      prior to and immediately after administration period, with significantly fewer
      lesions for regimen A after administration period (mean +/- SD A:B = 2.6 +/-
      3.2:9.5 +/- 8.5; p = 0.027). CONCLUSIONS: Combination therapy with GGA and
      rabeprazole reduced the incidence of gastroenteropathy induced by 1-week
      administration of diclofenac. Our findings suggest this therapy as a candidate
      for protecting patients on long-term NSAID therapy.

PMID- 19844110
TI  - Volume therapy and cardiocircular function during hyperthermic intraperitoneal
      chemotherapy.
AB  - BACKGROUND: Surgical cytoreduction and simultaneous hyperthermic intraoperative
      intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis is afflicted
      with a high incidence of postoperative complications. The knowledge of
      intraoperative volume therapy during surgery and chemotherapy is limited. On the
      other hand, the choice of a 'liberal' or 'restrictive' regimen of fluid
      administration has a deep impact on the postoperative morbidity. The aim of this
      observational trial was to report detailed data on volume replacement and
      cardiocircular function during the HIPEC procedure. METHODS: Eighteen consecutive
      patients undergoing cytoreductive surgery and HIPEC for peritoneal carcinomatosis
      were enrolled. The intraoperative volume administration was observed as well as
      the postoperative morbidity and mortality. Cardiofunctional data were assessed by
      the invasive transthoracic thermodilution technique. RESULTS: The study showed
      that large amounts of volume (1,240 ml h(-1); range: 810-1,570 ml h(-1)) are
      given during the HIPEC procedure to replace fluid loss and maintain a stable
      circulatory function. Signs of a hyperdynamic status during intraoperative
      intraperitoneal chemotherapy were not found. CONCLUSIONS: During surgical
      cytoreduction and simultaneous HIPEC, large amounts of volume were administered.
      HIPEC in itself did not lead to an increased fluid requirement. Further
      prospective studies with larger populations are needed to investigate whether
      goal-oriented therapies and a restricted volume regimen can contribute to
      decrease the postoperative morbidity.

PMID- 19844111
TI  - Endocrine regulation of feto-placental growth.
AB  - Hormones are both growth stimulatory and growth inhibitory in utero. They
      regulate tissue growth and development by controlling the rates of cell
      proliferation, apoptosis and differentiation in many fetal tissues. They also
      signal the level of resources available for intrauterine growth to the fetal
      tissues and relay back to the placenta the degree of mismatch between the actual
      fetal nutrient supply and the fetal nutrient demands for growth. They affect
      intrauterine growth by anabolic and catabolic actions on fetal metabolism and by
      altering the nutrient transfer capacity and endocrine function of the placenta.
      By modifying the fetal growth trajectory, hormones have a central role in
      programming development in utero and in determining the phenotypic outcome of
      changes in feto-placental growth during adverse intrauterine conditions. This
      review examines the role of hormones in feto-placental growth with particular
      emphasis on insulin, the insulin-like growth factors and glucocorticoids.

PMID- 19844112
TI  - Regulation of pituitary function by cytokines.
AB  - Research performed on the pituitary has proven that cytokines play an important
      role in maintaining pituitary physiology, affecting not only cell proliferation
      but also hormone secretion. The effects of cytokines can be autocrine or
      paracrine. This review gives an overview on the effects of the most studied
      cytokines in the pituitary. Special interest is focused on interleukin-6 (IL-6)
      because it has the distinctive characteristic of stimulating pituitary tumor cell
      growth, but has the opposite effect on normal pituitary cells. On the other hand,
      IL-6 is a cytokine of interest in the pituitary because recent work has shown
      that it promotes and maintains senescence in certain types of tumors. Given that
      the majority of pituitary adenomas are microadenomas and the fact that clinically
      inapparent pituitary tumors are quite common, senescence, perhaps mediated by IL
      6, is an attractive mechanism for explaining the benign nature of pituitary
      tumors.

PMID- 19844113
TI  - First two years' response to growth hormone treatment in very young preterm small
      for gestational age children.
AB  - BACKGROUND: Growth hormone (GH) is a therapeutic option for small for gestational
      age (SGA) children without spontaneous catch-up. There are few reports on preterm
      SGA children. Prematurity is an additional risk factor for adult short stature.
      AIM: To describe GH efficacy in preterm SGA patients. METHODS: Twenty-five
      preterm SGA patients, 2-4 years old, treated with GH 0.066 mg/kg/day, were
      compared with 14 age-matched preterm SGA historical controls. Height, weight, IGF
      I, IGFBP-3, fasting glucose and insulin were measured every 6 months. RESULTS: At
      start of GH treatment, mean height and weight were -2.4 and -2.4 SDS,
      respectively. There was a significant increment in height SDS of 1.3 and 2.1
      during the 1st and the 2nd year of GH therapy, respectively. There was no
      significant difference between the progression of chronological and bone ages. A
      significant increase in IGF-I, IGFBP-3 and molar ratio was observed during GH
      therapy. There was no difference in glucose, insulin or HOMA-IR index.
      CONCLUSION: We showed for the first time that the height increment of preterm SGA
      with GH treatment is similar to that described in other studies with term SGA
      patients. Therefore, short-term GH treatment in a subset of preterm SGA patients
      between 2-4 years of age was able to promote adequate growth recovery with no
      excessive bone age acceleration or adverse effects on carbohydrate metabolism.

PMID- 19844114
TI  - Congenital adrenal hyperplasia due to 11-hydroxylase deficiency--insights from
      two novel CYP11B1 mutations (p.M92X, p.R453Q).
AB  - BACKGROUND: Steroid 11-hydroxylase (CYP11B1) deficiency (11OHD) is the second
      most common form of congenital adrenal hyperplasia (CAH). Herein, we describe two
      novel CYP11B1 mutations (g659_660dupTG, p.M92X; g.4817G>A, p.R453Q) found in a
      patient diagnosed with classic 11OHD, after presenting with borderline elevated
      17-hydroxyprogesterone concentrations in CAH newborn screening. METHODS: A novel
      CYP11B1 variant (p.R453Q) identified in a patient with classic 11OHD was
      characterized employing a COS7 cell assay and a computational three-dimensional
      CYP11B1 model. RESULTS: The in vitro expression analysis revealed an almost
      complete loss of function of p.R453Q. This finding was consistent with the
      clinical presentation of classic 11OHD as the patient was compound heterozygous
      for p.R453Q and a nonsense mutation (p.M92X) on the other allele. Inserting the
      p.R453Q mutation into our CYP11B1 model provided two potential explanations for
      the almost complete loss of enzyme activity. Firstly, the heme coordination is
      most likely disturbed. A second possibility could be an altered interaction with
      the redox partner adrenodoxin. CONCLUSION: Results indicate that both novel
      mutations are disease-causing mutations. Proving the pathogenic effect of a
      missense sequence variation is of particular importance for clinical genetic
      counseling as this provides essential information on the prediction of recurrence
      risk and disease severity.

PMID- 19844115
TI  - Effects of a twelve-week randomized intervention of exercise and/or diet on
      weight loss and weight maintenance, and other metabolic parameters in obese
      preadolescent children.
AB  - AIMS: To compare the short- and long-term effects of intervention programs on
      body weight and cardiometabolic risk factors. METHODS: 162 obese children (6-11
      years) were randomly assigned to three 12-week interventions with a 9-month
      follow-up period: exercise (E): 90 min moderate exercise 3 days/week (n = 52);
      diet (D): balanced hypocaloric diet, weekly meetings with dietician (n = 55), and
      diet + exercise (D+E) (n = 55). Changes in anthropometric variables,
      cardiometabolic profile and psychological outcome were assessed. RESULTS: At 12
      weeks BMI-SDS, cardiometabolic profiles, and psychological score improved in all
      groups. The decrease in BMI-SDS was greater in D and D+E compared with E (p <
      0.001), without a significant difference between the first two groups. Waist
      circumference and LDL cholesterol decreased more in D+E compared with E (p =
      0.026 and p = 0.038, respectively). The increase in adiponectin was greater in D
      and D+E compared with E (p = 0.004). Anthropometric and cardiometabolic variables
      regressed without significant differences between groups after 9 months. However,
      BMI-SDS, body fat percentage and LDL cholesterol were lower compared to baseline.
      CONCLUSIONS: Diet alone or combined with exercise are the most effective short
      term interventions for weight loss and improved cardiometabolic profiles, without
      a difference between them. In the long term, obese children need the long-term
      support of maintenance approaches.

PMID- 19844116
TI  - Growth without growth hormone and similar dysmorphic features in three patients
      with sporadic combined pituitary hormone deficiencies.
AB  - BACKGROUND/AIMS: Mutations in the HESX1 gene are associated with a broad spectrum
      of phenotypes: septo-optic dysplasia, midline defects, pituitary abnormalities
      with consequent hypopituitarism, isolated growth hormone (GH) deficiency or
      combined pituitary hormone deficiencies (CPHD). This study examined the
      prevalence of mutations in the HESX1 gene in patients with CPHD.
      PATIENTS/METHODS: Sixty patients with sporadic CPHD without septo-optic dysplasia
      were screened for mutations in HESX1. RESULTS: Three patients were found to be
      heterozygous for the same Asn125Ser variant in the HESX1 gene. In all 3,
      panhypopituitarism was presented in the neonatal period, manifested by severe
      hypoglycemia and neonatal jaundice in 2 patients and respiratory distress in 1.
      Remarkable findings from physical examination included coarse face; prominent,
      large, low-set ears; and skeletal abnormalities. Magnetic resonance imaging,
      performed in 2 patients, revealed a hypoplastic anterior and ectopic posterior
      pituitary without other midline anomalies. Despite persistent GH deficiency and
      undetectable levels of insulin-like growth factor 1, all patients had normal
      linear growth along the 10-25th percentile without GH therapy. CONCLUSION: The
      present study expands the clinical picture of HESX1 mutations by demonstrating
      that patients heterozygous for Asn125Ser may have a severe endocrinologic and
      neuroradiologic phenotype and similar dysmorphic features appearing very early in
      life.

PMID- 19844117
TI  - Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in
      croatia between 1995 and 2006.
AB  - AIMS: To evaluate the incidence, gender, symptoms and age at diagnosis among
      patients with classical congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency in Croatia. METHODS: Data were collected retrospectively
      for all classical CAH patients born or electively aborted following prenatal
      diagnosis between 01.01.1995 and 31.12.2006 and were compared with the data of
      the previously conducted study evaluating CAH patients discovered between 1964
      and 1984. RESULTS: During a 12-year period, 34 classical CAH patients were born.
      There were 20 salt-wasting (SW) (12 females/8 males) and 14 simple virilizing
      (SV) patients (7 females/7 males). If 3 female fetuses, electively aborted, were
      added, that would be a total of 37 CAH patients. With 532,942 live births and 34
      CAH patients born over this period, incidence of classical CAH was estimated to
      1:15,574 or 1:14,403 if 3 electively aborted fetuses were included. The lower
      incidence of SW boys compared to SW girls (8:12) and similar number of SW and SV
      boys (8:7) indicate that substantial proportion of SW boys die unrecognized.
      Owing to better health care, diagnosis was established significantly earlier in
      SW and SV girls compared to the period of 1964-1984 (p < 0.003). During 1995
      2006, none of the patients died following the diagnosis of CAH, and there was no
      erroneous sex assignment. CONCLUSION: Despite of improvement in health care,
      diagnosis of CAH in Croatia is still delayed and some of the patients go
      unrecognized or die. Therefore, we think that the results of our study support
      the need for the introduction of newborn screening.

PMID- 19844118
TI  - Isolated Cushing's syndrome: an unusual presentation of McCune-Albright syndrome
      in the neonatal period.
AB  - Cushing's syndrome (CS) may develop at any time in childhood. In the neonatal
      period, the major cause is the overactivation of adrenal cells within the context
      of McCune-Albright syndrome (MAS). The hypercorticism usually appears with other
      clinical signs of MAS. We report here a case of isolated neonatal CS as the
      initial evidence of MAS. This newborn girl was referred to our pediatric
      endocrine unit at the age of 3 months for hypotonia and growth retardation.
      Clinical examination revealed facial plethora, moon face, and swollen limbs.
      Laboratory data demonstrated ACTH-independent CS. Magnetic resonance imaging
      showed moderate bilateral adrenal hyperplasia, though more marked in the left
      adrenal gland, without nodules. This peripheral hypercorticism without well
      defined adrenal tumor was suggestive of MAS, although no other signs like
      precocious puberty or cafe-au-lait spots were found. An activating Gsalpha gene
      mutation was found on DNA extracted from blood. Because MAS is a somatic disease,
      usually with unilateral effects, we tried to remove only the larger adrenal
      gland, where the mutation was demonstrated. This female newborn later developed
      the classical triad of MAS, reinforcing this diagnosis. Cushing's syndrome in
      infants, even when isolated, may suggest a diagnosis of MAS.

PMID- 19844119
TI  - Monozygotic twins are generally discordant for congenital hypothyroidism from
      thyroid dysgenesis.

PMID- 19844120
TI  - Genetic and clinical spectrum of aromatase deficiency in infancy, childhood and
      adolescence.
AB  - INTRODUCTION: cP450aromatase deficiency provides clues for the understanding of
      the role of aromatase in prepubertal and pubertal human health and disease.
      Placental aromatization of androgens protects the female fetus against the
      virilizing action of fetal androgens. After birth, the dual effect of aromatase
      deficiency, excessive androgens, and insufficient estrogens is responsible for a
      variable clinical picture. Nineteen cases of aromatase gene (CYP19) deficiency
      have been reported. PHENOTYPE: Phenotype is dependent on sex and age. In
      newborns, aromatase deficiency should be considered in the etiology of 46,XX DSD,
      after ruling out congenital adrenal hyperplasia. In prepubertal aromatase
      deficient girls, high levels of ovarian androgens and gonadotropins facilitate
      the formation of ovarian cysts. Bone mineralization can be affected and bone
      aging is delayed. In pubertal girls, there is poor sexual development and
      abnormal virilization. The phenotype may be variable according to enzyme activity
      level. Insulin sensitivity may be abnormal in both men and women. Finally,
      aromatase might also play a role in the regulation of testicular cell mass in the
      newborn testis. CONCLUSION: Adequate interpretation of clinical data should lead
      to the analysis of the CYP19 gene for diagnostic confirmation and implementation
      of appropriate management.

PMID- 19844121
TI  - Evaluation of adrenomedullary function in patients with congenital adrenal
      hyperplasia.
AB  - BACKGROUND/AIMS: Congenital adrenal hyperplasia (CAH) is characterized by adrenal
      insufficiency with or without salt wasting. It is also accompanied by
      adrenomedullary hypofunction. The aim of the present study was to investigate
      adrenomedullary function in patients with CAH due to 21-hydroxylase and 11beta
      hydroxylase deficiencies and in age-matched normal subjects. METHODS: We measured
      plasma catecholamines (epinephrine and norepinephrine) and urine metanephrine in
      44 patients with CAH, 32 due to 21-hydroxylase deficiency (17 patients with the
      salt-wasting form and 15 patients with the simple virilizing form), and 12 due to
      11beta-hydroxylase deficiency, and in 25 healthy controls. RESULTS: Plasma
      epinephrine and urine metanephrine levels were significantly higher in the
      controls than in patients with CAH (p = 0.02 and p < 0.001, respectively). Plasma
      norepinephrine levels were significantly lower in the controls than in patients
      with CAH (p < 0.001). Interestingly, patients with the salt-wasting form had
      lower norepinephrine levels in comparison to the other subgroups of CAH.
      CONCLUSION: Despite the fact that CAH patients have insufficient epinephrine
      secretion, these patients have the ability to increase compensatory
      norepinephrine. However, this increase is much lower in patients with the salt
      wasting form. These findings need to be confirmed by other studies.

PMID- 19844122
TI  - A favorable metabolic and antiatherogenic profile in carriers of CYP21A2 gene
      mutations supports the theory of a survival advantage in this population.
AB  - CONTEXT: The very high carrier frequency of 21-hydroxylase deficiency worldwide
      has been postulated as indicating a survival advantage. The 'mediators' of such
      an effect remain speculative. OBJECTIVE: To look for possible differences in the
      metabolic and atherogenic risk profile of carriers and noncarriers of CYP21A2
      gene mutations at puberty in order to identify possible mediators of the presumed
      survival advantage for the carriers. It is anticipated that by studying
      atherogenic risk factors at such an early developmental stage, age-related
      alterations in these factors may be minimized. METHODS: The study group included
      45 adolescent girls diagnosed in our center with premature pubarche, 29 of whom
      were noncarriers and 16 carriers of CYP21A2 mutations. The two groups did not
      differ in chronological age, age at pubarche or menarche, pubertal stage, body
      mass index and waist-to-hip ratio. Biochemical and hormonal profile markers as
      well as markers of endothelial dysfunction were determined by appropriate
      methodology. Additionally, in each subject, an oral glucose tolerance test and a
      gonadotrophin-releasing hormone GnRH analogue stimulation test were carried out.
      RESULTS: Endothelin-1 values were lower in the carriers compared to the
      noncarriers (p = 0.031). Higher tissue plasminogen activator and lower
      plasminogen activator inhibitor-1 values were found in carriers compared to
      noncarriers (p = 0.02 and <0.001, respectively). The ratio of the insulinogenic
      index/homeostasis model assessment for insulin resistance, which reflects beta
      cell function, was higher in carriers (p = 0.048), indicating a more favorable
      beta-cell function in the carriers. CONCLUSIONS: Our findings that carriers of
      CYP21A2 gene mutations have a more favorable internal milieu with regard to the
      metabolic syndrome and atherogenesis support the theory that heterozygous CYP21A2
      mutations provide a survival advantage. The mechanisms involved may be related to
      the insulin secretion-action pathway, hypothalamic-pituitary-adrenal axis
      responsiveness or other still unrecognized factors.

PMID- 19844123
TI  - Perinatal goiter with increased iodine uptake and hypothyroidism due to excess
      maternal iodine ingestion.
AB  - BACKGROUND/AIMS: To review cases of fetal/newborn goiter due to excess maternal
      iodine ingestion. METHODS: We reviewed the medical records of all patients that
      presented with congenital goiter in 2003. We used the PubMed search engine to
      conduct a review of publications addressing congenital goiter and excessive
      iodine intake. RESULTS: Maternal ingestion of large amounts of iodine due to an
      error in the manufacturing of a prenatal vitamin caused a goiter in her fetus.
      Seven other women who received the same prenatal vitamin had newborn children
      with goiters. Three of these children were hypothyroid at the time of initial
      examination. Three patients (2 hypothyroid and 1 euthyroid) had thyroid scans
      with radioactive iodine; iodine uptake was elevated (>80%) in all 3, and in 1 the
      perchlorate washout test was positive. CONCLUSION: The finding of congenital
      goiter and increased iodine uptake in a newborn is considered diagnostic of
      dyshormonogenesis, a permanent form of hypothyroidism. Our description is
      important because it demonstrates that iodine excess during pregnancy may mimic
      some forms of dyshormonogenesis. The differentiation between the two causes of
      newborn goiter may prevent the lifelong use of supplemental levothyroxine in
      patients with a transient abnormality.

PMID- 19844124
TI  - Isolation and characterization of omental adipose progenitor cells in children: a
      potential tool to unravel the pathogenesis of metabolic syndrome.
AB  - BACKGROUND/AIM: Visceral adipose tissue plays a pivotal role in the pathogenesis
      of metabolic syndrome. Several investigations refer to the physiology of
      subcutaneous and visceral adipose tissue of adult obese subjects, focusing on the
      characterization of adipose-derived stem cells and their differentiation
      capacity. To date, no study has been carried out on visceral adipose tissue of
      children, the main limitation being the amount of fat tissue available. The aim
      of this investigation was to establish a method to successfully isolate adipose
      progenitor cells from very small specimens of omental fat obtained from children
      undergoing abdominal surgery. METHODS: A previously described procedure employed
      to extract adipose progenitors from large amounts of lipoaspirate was modified.
      0.5-cm(3) specimens of omental fat were collected from 13 children and 2
      newborns. Primary, secondary and higher passaged adipocytic progenitor cell
      cultures were established. Immunophenotyping of the generated lines was carried
      out by flow cytometry analysis. Differentiation experiments concerning the
      adipogenic phenotype were conducted. RESULTS: A feasible method for isolating
      adipose progenitors from pediatric specimens of omental fat was established.
      Cells showed a fibroblast-like appearance consistent with that of mesenchymal
      stem cells obtained from bone marrow. The mesenchymal phenotype was confirmed by
      the surface antigenic profile of these cells. Cells also underwent adipogenic
      differentiation in vitro. CONCLUSION: The availability of progenitor primary cell
      lines from omental adipose tissue of children may allow future investigations
      aimed at unraveling whether fetal programming of adipogenesis is responsible for
      the pathogenesis of the metabolic syndrome that develops during adulthood in
      subjects, born with low birth weight, typically showing central fat
      redistribution.

PMID- 19844125
TI  - Seven years of safety and efficacy of the recombinant human growth hormone
      Omnitrope in the treatment of growth hormone deficient children: results of a
      phase III study.
AB  - AIM: This phase III clinical study in growth hormone deficiency (GHD) children
      with growth retardation was designed to compare efficacy and safety of
      Omnitrope((R)) with Genotropin((R)) and assess the long-term safety and efficacy
      of Omnitrope((R)). The results of 7 years of treatment with Omnitrope((R)) are
      presented. PATIENTS AND METHODS: Eighty-nine treatment-naive, prepubertal
      children with GHD were randomized (part 1) to Omnitrope((R)) lyophilisate (group
      A, n = 44) or Genotropin((R)) (group B, n = 45) for 9 months and received a
      subcutaneous dose of 0.03 mg/kg/day. In part 2, patients receiving
      Omnitrope((R))lyophilisate continued the same treatment for a further 6 months,
      while patients on Genotropin((R)) were switched to Omnitrope((R)) liquid for the
      subsequent 6 months. In part 3, patients in both groups received
      Omnitrope((R))liquid for a period up to 69 months. RESULTS: The development of
      the 4 auxological parameters (height, height SD score, height velocity and height
      velocity SD score) and IGF-1 and IGFBP-3 levels were comparable between both
      groups of patients and confirmed the well-known growth response of GHD children
      to recombinant human GH treatment. Omnitrope((R)) was well tolerated and safe
      over 7 years of treatment. CONCLUSION: The clinical comparability between
      Omnitrope((R)) and Genotropin((R)) was demonstrated within 9 months of treatment.
      Long-term safety and efficacy of 7 years of treatment with Omnitrope((R)) was
      proven.

PMID- 19844126
TI  - Metformin, estrogen replacement therapy and gonadotropin inhibition fail to
      improve insulin sensitivity in a girl with aromatase deficiency.
AB  - BACKGROUND: Insulin resistance (IR), abnormal lipid profile, and other features
      of the metabolic syndrome have been described in CYP19 gene knockout mice and in
      aromatase-deficient adult men but not in prepubertal affected girls. AIMS: To
      study insulin sensitivity, as well as the effects of estrogen, metformin and
      GnRHa treatment on glucose homeostasis, in an aromatase-deficient girl. METHODS:
      Clinical, metabolic and hormonal follow-up data, from 8 to 12 years of age, is
      presented. RESULTS: At 9 years of age, IR (HOMA 5.6) and glucose intolerance was
      detected, along with high serum testosterone (2.28 nmol/l), androstenedione (4.92
      nmol/l) and FSH (13.4 mIU/ml) levels. Estrogen replacement was ineffective to
      suppress gonadotropin and androgen levels, as well as IR. Under metformin
      therapy, she developed type 2 diabetes and acanthosis nigricans. GnRHa
      administration for 1 year resulted in marked decreases in gonadotropin and serum
      androgens, but severe IR persisted. CONCLUSION: Postnatal estrogen replacement
      and a marked decrease of endogenous androgens failed to improve IR and glucose
      tolerance. We propose that, in females, the increment of androgens and/or lack of
      estrogens during fetal life might alter the mechanism of fetal programming of
      insulin sensitivity.

PMID- 19844127
TI  - The major cat allergen, Fel d 1, in diagnosis and therapy.
AB  - Sensitization to cat is a common cause of allergic disease all over the world.
      Symptoms range from mild rhinoconjunctivitis to potentially life-threatening
      asthmatic exacerbations. In vivo and in vitro diagnostics of cat allergy is
      currently based on cat dander extract. As allergen extracts from natural sources
      are heterogeneous in composition, the allergen content may vary. With the
      introduction of allergens produced by recombinant techniques, a large panel of
      recombinant allergenic molecules including the major cat allergen, recombinant
      Fel d 1, has become available for immunological investigations, diagnosis and
      treatment. Studies have shown that this single allergen, which belongs to the
      uteroglobin protein family, is at least as good as cat dander extract in
      identifying cat-allergic patients. The introduction of recombinant Fel d 1-based
      tests into clinical practice will increase our knowledge of this single allergen
      molecule as a diagnostic tool and improve the selection for therapy of cat
      allergy. Several different modes for allergen-specific immunotherapy of cat
      allergy based on Fel d 1 have been developed. These include Fel d 1 hypoallergens
      and allergen constructs where Fel d 1 is coupled to immunomodulatory proteins or
      carriers. The approaches have been evaluated in experimental in vitro and in vivo
      model systems with promising results. In addition, immunotherapy with Fel d 1
      peptides containing T-cell epitopes has been tested in clinical trials. After
      initial problems with adverse reactions, more recent data show that peptide
      immunotherapy modulates the immune response to Fel d 1 and reduces early- and
      late-phase effector reactions in cat-allergic patients.

PMID- 19844129
TI  - Th17 immunity in patients with allergic asthma.
AB  - BACKGROUND: Allergic asthma is an inflammatory disease regulated by the T helper
      (Th) cells. The Th1/Th2 imbalance has been well documented in the pathogenesis of
      allergic asthma. Recently, Th17 cells have been found to participate in the
      development of allergic asthma in animals. However, whether Th17 immunity
      contributes to the systemic immune responses in allergic asthmatic patients is
      unclear. METHODS: Peripheral blood mononuclear cells were isolated from allergic
      asthmatics (n = 29) and healthy controls (n = 12). The frequencies of Th1, Th2
      and Th17 cells were analyzed by flow cytometry. The related cytokine (IFN-gamma,
      IL-4, IL-17, IL-22, IL-23 and IL-25) concentrations in plasma and culture
      supernatants were measured by enzyme-linked immunosorbent assay and Luminex. The
      level of retinoic acid-related orphan receptor gammat (RORgammat), a key
      transcription factor controlling Th17 differentiation, was examined by real-time
      quantitative polymerase chain reaction. RESULTS: The percentages of Th2 and Th17
      cells as well as the concentrations of Th2- and Th17-related cytokines were
      higher in allergic asthmatics than those in healthy controls; some patients were
      even treated with inhaled glucocorticoid. The percentages of Th17 cells as well
      as the plasma concentrations of IL-17 and IL-22 tended to increase with the
      severity of the disease, while the IL-25 level was elevated in mild patients. A
      parallel elevation of IL-17 and IL-23 concentrations and an increase in RORgammat
      level were found in allergic asthmatics. CONCLUSION: Our results suggest that
      besides predominant Th2 immunity, abnormal Th17 immunity may be also involved in
      the pathogenesis of allergic asthma.

PMID- 19844128
TI  - Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines
      from human basophils during omalizumab therapy.
AB  - BACKGROUND: Treating asthmatics with the humanized IgE-scavenging antibody,
      omalizumab (rhuMAb-E25, Xolair, reduces airways inflammation and asthma symptoms.
      Previously, omalizumab was shown to cause a dramatic and reversible loss of cell
      surface high-affinity IgE receptors, FcepsilonRI, from the peripheral blood
      basophils of asthmatics. The consequences of receptor loss for the FcepsilonRI
      mediated synthesis and release of cytokines implicated in allergic asthma have
      not been examined. METHODS: Fifteen asthmatic volunteers each received omalizumab
      for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks
      after and 6 months after omalizumab. Basophils were assayed for the basal and
      anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data
      were analyzed by repeated measures ANOVA and by paired t tests. RESULTS: Anti-IgE
      stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and
      chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL
      8 was reduced during omalizumab treatment and returned to pretreatment levels
      after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels
      or basal and anti-IgE-stimulated histamine release. CONCLUSIONS: Omalizumab may
      reduce asthma symptoms in part by suppressing the FcepsilonRI-mediated production
      by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated
      basophil cytokine synthesis appears more sensitive than histamine release to the
      loss of FcepsilonRI caused by omalizumab treatment.

PMID- 19844130
TI  - Functional subtypes of renal alpha1-adrenoceptor in spontaneously hypertensive
      rats with streptozotocin-induced experimental diabetic nephropathy.
AB  - AIM: This study investigated the impact of hypertension combined with diabetic
      nephropathy on rat renal alpha(1)-adrenoceptor subtype composition. METHODS: In
      streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic
      nephropathy developed as reflected by increased kidney index, plasma creatinine,
      albumin excretion, creatinine clearance and fractional excretion of Na(+) (all p
      < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves
      and intrarenally administered noradrenaline (alpha-adrenoceptor agonist),
      phenylephrine (alpha(1)-adrenoceptor agonist) and methoxamine (alpha(1A)
      adrenoceptor agonist) were determined in the presence and absence of intrarenally
      administered amlodipine (Ca(2+) channel blocker), 5-methylurapidil (alpha(1A)
      adrenoceptor antagonist), chloroethylclonidine (alpha(1B)-adrenoceptor
      antagonist) and BMY 7378 (alpha(1D)-adrenoceptor antagonist). RESULTS: In
      diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of
      all adrenergically induced vasoconstrictor responses in the antagonists, except
      chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of
      the responses. CONCLUSION: The data demonstrated that there was a functional
      coexistence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of
      SHR irrespective of the presence of diabetic nephropathy. However, there was a
      minor contribution of pre-synaptic alpha-adrenoceptors to the adrenergically
      mediated vasoconstrictor responses in the diabetic nephropathy SHR.

PMID- 19844131
TI  - Role of lipoxygenases and lipoxin A(4)/annexin-1 receptor in gastric protection
      induced by 20% ethanol or sodium salicylate in rats.
AB  - The role of cyclooxygenases and prostaglandins in experimental models of
      gastroprotection is well established. We investigated the effects of the 5
      lipoxygenase inhibitor A63162, the 12-lipoxygenase inhibitor baicalein and the 15
      lipoxygenase inhibitor PD146176 as well as the nonspecific lipoxin A(4)/annexin-1
      antagonist Boc1 on adaptive protection induced by 20% ethanol against 70%
      ethanol, and on protection induced by sodium salicylate against the mucosal
      damage-aggravating effects of celecoxib and dexamethasone during local ischemia
      reperfusion in rats. It was found that both types of gastroprotection were
      antagonized by the lipoxygenase inhibitors and the lipoxin A(4)/annexin-1
      antagonist in doses that have no direct damaging effect on gastric mucosa. The
      results suggest that not only cyclooxygenases, but also active lipoxygenases and,
      possibly, annexin-1 are required for these types of gastroprotection to occur.

PMID- 19844132
TI  - Plasma cardiac necrosis markers C-troponin I and creatine kinase, associated with
      increased malondialdehyde levels, induced in rabbits by means of 5-aminolevulinic
      acid injection.
AB  - A number of papers have described high levels of 5-aminolevulinic acid in cases
      of heart damage due to acute myocardial infarction, acute intermittent porphyria
      or chronic kidney failure, but it is not known whether the heart damage is
      directly associated with 5-aminolevulinic acid. The aim of this study was to
      verify whether such an association exists by injecting rabbits with 5
      aminolevulinic acid and searching for the appearance of cardiac necrosis markers
      and histological heart alterations, and investigate whether the cardiotoxic
      activity of 5-aminolevulinic acid may involve peroxidation by seeking the
      presence of the peroxide marker malondialdehyde. The administration of 5
      aminolevulinic acid led to the appearance of c-troponin I and creatine kinase,
      induced histological heart alterations and increased the malondialdehyde levels.
      The plasma levels of malondialdehyde and cardiac necrosis markers were also
      measured after the injection of 5-aminolevulinic acid in combination with the
      daunorubicin agent inducing peroxidation. The combined administration very
      significantly increased the plasma levels of 5-aminolevulinic acid,
      malondialdehyde, and the cardiac necrosis markers c-troponin I and creatine
      kinase. It therefore seems that there is a close relationship between altered 5
      aminolevulinic acid levels, malondialdehyde and cardiac necrosis markers, which
      is attributable to the capacity of 5-aminolevulinic acid to generate toxic oxygen
      species that damage the heart. High plasma 5-aminolevulinic acid levels should be
      considered a factor contributing to cardiotoxicity and to the appearance of
      cardiac necrosis markers.

PMID- 19844133
TI  - Gender-based differences in drug prescription: relation to adverse drug
      reactions.
AB  - BACKGROUND/AIM: The female gender appears to suffer from more adverse drug
      reactions (ADRs) than the male gender. So far, there has been no epidemiologic
      study analyzing gender-based differences in drug prescribing and its ADR risks.
      The aim of the present study was to establish a drug risk stratification adjusted
      to age, number of prescriptions and drug classes with respect to gender
      differences based on intensive data acquisition methods. METHOD: A prospective
      multicenter study was conducted in several departments in Germany and Israel
      (pediatrics, medicine and geriatrics) enclosing 2,371 inpatients. RESULTS: A
      total of 25,532 drug prescriptions during hospitalization were evaluated. At
      least 1 ADR was found in 774 patients (32.6%). Drugs for the cardiovascular
      system, nervous system, alimentary tract and musculoskeletal system were
      prescribed most often in females. The following drug classes led significantly
      more often to ADRs in women as compared to men: alimentary tract (OR 0.5; p =
      0.0002), cardiovascular system (OR 0.72; p = 0.0140), musculoskeletal system (OR
      0.31; p = 0.0004) and nervous system (OR 0.62; p = 0.0023). After adjustment to
      age, total number of prescriptions and drug class, only anti-infectives
      (antibacterials) and musculoskeletal system (anti-inflammatory) drugs stand out
      as causing more ADRs in women. CONCLUSION: Antibacterials and anti-inflammatory
      agents cause more ADRs in females as compared to males.

PMID- 19844134
TI  - Prevalence of and factors affecting pulmonary hypertension in hemodialysis
      patients.
AB  - BACKGROUND: Pulmonary hypertension (PH) has been reported to be high among end
      stage renal disease (ESRD) patients. OBJECTIVES: The aim of this study was to
      investigate the role of arteriovenous fistula (AVF) flow in the pathogenesis of
      PH and the prevalence of PH in patients with chronic renal failure (CRF) and to
      suggest other possible etiologic factors. METHODS: The prevalence of PH was
      prospectively estimated by Doppler echocardiography in 116 ESRD patients on
      regular hemodialysis (HD). Laboratory and clinical variables were compared
      between patients with and without PH (groups 1 and 2, respectively). PH was
      defined as systolic pulmonary artery pressure (SPAP) over 30 mm Hg. Patients with
      PH underwent further evaluation by 2 pulmonologists. AVF flow was measured by
      Doppler ultrasonography. Blood tests including arterial blood gases, hemoglobin,
      serum calcium, phosphorus and parathyroid hormone were determined. RESULTS: PH
      was found in 25 (21.6%) patients (group 1) with an SPAP of 37.9 +/- 2.8 mm Hg.
      Mean AVF flow was increased (1,554 +/- 207.60 ml/min) in group 1. Left
      ventricular ejection fraction (LVEF) was significantly different between the 2
      groups (55.3 +/- 11.5 and 64.4 +/- 40, respectively; p < 0.05). Neither
      significant primary lung disease nor parenchymal lesions were detected in group
      1. PH showed a significant difference for cigarette smoking (p < 0.05). In group
      1 the prevalence of cigarette smoking was higher. The main etiology of CRF was
      diabetes mellitus with a ratio of 44% in group 1. CONCLUSION: Our study
      demonstrated a surprisingly high prevalence of PH among patients receiving long
      term HD. PH was related to high AVF flow, low LVEF and cigarette smoking. AVF
      flow and cigarette smoking are important correctable causes of PH. Early
      detection is important in order to avoid the serious consequences.

PMID- 19844135
TI  - Narrow band imaging applied to pleuroscopy for the assessment of vascular
      patterns of the pleura.
AB  - BACKGROUND: Narrow band imaging (NBI), which enhances blood vessels, is a new
      endoscopic technology for diagnosing malignancies, but it has not been
      investigated for pleuroscopy. OBJECTIVES: To evaluate the efficacy of NBI applied
      to pleuroscopy for detecting malignant lesions by assessing vascular patterns of
      the pleura. METHODS: From May 2006 to September 2008, 45 patients with
      undiagnosed pleural ef-fusion underwent pleuroscopy using a pleura-videoscope
      with white light (WL) and NBI under local anesthesia. For this prospective study,
      73 biopsy specimens were obtained from sites where images under both WL and NBI
      were recorded and classified regarding vascular patterns. RESULTS: Of the 73
      lesions, WL showed blood vessels in 32 lesions, and NBI in 52 lesions (WL vs.
      NBI; p = 0.0014). The accuracy, sensitivity and specificity in the detection of
      irregular vascular patterns, e.g. blood vessels with irregular caliber or
      punctate vessels indicating malignant lesions, were 60.3, 76.5 and 55.4% in WL,
      and 80.8, 85.3 and 76.9% in NBI, respectively, resulting in a significant
      increase in NBI (p = 0.0106 for accuracy and p = 0.0494 for specificity). For
      flat lesions, NBI revealed a higher accuracy rate (90.6%) in the detection of
      irregular vascular patterns indicating malignant lesions. CONCLUSION: Our study
      demonstrated that NBI applied to pleuroscopy displayed blood vessels
      significantly better than WL. NBI was useful to detect irregular vascular
      patterns suggesting malignant lesions, especially for flat lesions. Therefore,
      NBI was considered useful in the selection of optimal biopsy sites by assessing
      vascular patterns.

PMID- 19844136
TI  - Parasagittal transinsular electrodes for stereo-EEG in temporal and insular lobe
      epilepsies.
AB  - OBJECTIVE: Direct invasive EEG recordings of the insula - due to its particular
      anatomical position, deeply seated between both opercula - can only be performed
      with intracerebral electrodes. To date, the technique most commonly used for
      insular stereoelectroencephalography (SEEG) is the orthogonal-transopercular
      electrode approach with the Talairach methodology. We propose another technique
      utilizing MRI with transinsular parasagittal electrodes and a posterior entry
      point. This avoids passing through the opercula and sylvian vessels running over
      the insular surface. METHODS: Nine patients, whose seizures implicated the
      insula, underwent brain surgery. Under general anesthesia with a Leksell frame,
      3D-T(1) SPGR MRI with gadolinium enhancement was achieved. Surgical planning was
      performed using the StealthStation with an entry point in the parieto-occipital
      junction setting the target for the first contact of the lead at the most
      anterior part of the insula. The trajectory was manipulated in order to have at
      least 4 contacts per electrode track within the insular cortex. All patients had
      a postoperative MRI to verify the exact position of each contact. RESULTS:
      Insular seizures were recorded in all patients. There was neither intracranial
      bleeding nor infection. In all of the cases, except 1, the seizures recorded were
      found to be propagations of the primary epileptic zone located in the temporal
      lobe, either in the mesial structures or the superior temporal gyrus. Eight
      patients were operated, 7 with an antero-mesial temporal lobectomy and 1 with
      dysplasia of the superior temporal gyrus. No insular resections were performed.
      CONCLUSION: We report a novel technique for insular SEEG with parasagittal
      electrodes, parallel to the insular cortex, with an entry point at the parieto
      occipital junction. This technique is based entirely on use of MRI, and avoids
      passing through the opercula and sylvian vessels.

PMID- 19844137
TI  - Chronic deep brain stimulation for segmental dystonia.
AB  - Fourteen consecutive patients with segmental dystonia underwent chronic deep
      brain stimulation (DBS) surgery in the frame of a prospective study protocol.
      Twelve patients received chronic pallidal stimulation, while 2 patients with
      prominent dystonic tremor received chronic thalamic ventrointermediate nucleus
      stimulation. Twelve patients had primary dystonia, and 2 patients secondary
      dystonia. The Burke-Fahn-Marsden dystonia rating scale (BFM motor) showed a mean
      relative improvement of 57.3% at the first follow-up (FU1, mean 7 months) and
      57.8% at the second follow-up (FU2, mean 16 months). The mean BFM scores were
      34.9 +/- 17.7 preoperatively, 14.9 +/- 11.7 at FU1, and 14.8 +/- 10.3 at FU2.
      Scores of the disability subscale improved by 43% at FU1 and 36% at FU2.
      Improvement was comparatively less in those patients with secondary dystonia.
      Dysarthria was a limitation of DBS in 4 patients when using high voltage.
      Overall, chronic DBS is a very effective treatment option for medically
      refractory segmental dystonia.

PMID- 19844139
TI  - [Evaluation of severity in acute pancreatitis].
AB  - Acute pancreatitis has a variable etiology and natural history, and some patients
      have severe complications with a significant risk of death. The prediction of
      severe disease should be achieved by careful ongoing clinical assessment coupled
      with the use of a multiple factor scoring system and imaging studies. Over the
      past 30 years several scoring systems have been developed to predict the severity
      of acute pancreatitis. However, there are no complete scoring index with high
      sensitivity and specificity till now. The interest in new biological markers and
      predictive models for identifying severe acute pancreatitis testifies to the
      continued clinical importance of early severity prediction. Among them, IL-6, IL
      10, procalcitonin, and trypsinogen activation peptide are most likely to be used
      in clinical practice as predictors of severity. Even if contrast-enhanced CT has
      been considered the gold standard for diagnosing pancreatic necrosis, early
      scanning for the prediction of severity is limited because the full extent of
      pancreatic necrosis may not develop within the first 48 hour of presentation.

PMID- 19844138
TI  - [A case of caroli disease with biliary stones].

PMID- 19844140
TI  - [Comparision between proximal gastrectomy and total gastrectomy in early gastric
      cancer].
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate clinical outcome of
      proximal and total gastrectomy regarding reflux esophagitis, nutritional state,
      and anemia in early gastric cancer. METHODS: 94 patients with early gastric
      cancer were included from January 2001 to January 2007 at Chungnam National
      University Hospital. Of whom 40 patients (31 men and 9 woman) had proximal
      gastrectomy (PG) and 54 patients (44 men and 10 woman) had total gastrectomy
      (TG). We reviewed all their medical and surgical record with surveying for
      gastrointestinal symptoms and reflux symptoms over the phone. RESULTS: There were
      no significant differences between basic, surgical, and histopathologic
      characteristics. Bile reflux symptoms and heart burn symptoms were more common
      and severe in the TG group. The incidences of endoscopically detected reflux
      esophagitis were about 60% in the TG group and about 30% in the PG group. The
      hemoglobin levels were significantly higher in the PG group after the operation
      and were gradually decreased in the TG as the time went. The levels of laboratory
      variables such as total protein, albumin, and total cholesterol were lower in the
      TG group than in the PG group after the operation. However, stoma stricture after
      operation developed in the PG group more often than in the TG group, and
      esophageal balloon dilatations were performed more frequently in the PG group.
      CONCLUSIONS: PG is favorable for proximal early gastric cancer in terms of
      reduced reflux esophagitis, anemia, and malnutrition except the stricture at
      esophagogastrostomy site.

PMID- 19844141
TI  - [Prevalence of colorectal adenoma is increased in patients with gastric adenoma].
AB  - BACKGROUND/AIMS: It has been reported that patients with gastric cancer may be at
      increased risk of synchronous or metachronous colorectal cancer. However, the
      incidence of colorectal adenoma in patients with gastric adenoma has not been
      discussed earlier. The aims of this study were to investigate the incidence of
      colorectal adenoma and to evaluate the necessity of colonoscopic surveillance in
      patients with gastric adenoma. METHODS: We performed colonoscopy in 221 patients
      with gastric adenoma between January 2002 and June 2008. As a control group, 387
      consecutive patients without gastric adenoma on gastroscopy who underwent
      colonoscopy were included. We retrospectively examined the endoscopic and
      colonoscopic findings as well as the clinicopathologic features. RESULTS:
      Colorectal adenoma were diagnosed in 57.5% (127/221) of the gastric adenoma group
      and 38.0% (147/387) of the control group (p<0.001). Univariate analysis
      demonstrated that gender, age, past history of diabetes, and past history of
      gastric adenoma were associated with the risk of colorectal adenoma. Multivariate
      analysis demonstrated that gender (male, aOR 2.31, 95% CI 1.61-3.31), age (> or
      =50 years, aOR 2.47, 95% CI 1.53-4.01), past history of diabetes (aOR 2.35, 95%
      CI 1.32-4.20), and presence of gastric adenoma (aOR 1.63, 95% CI 1.13-2.36)
      appeared to be independent risk factors for colorectal adenoma. CONCLUSIONS: The
      risk of colorectal adenoma increases significantly in patients with gastric
      adenoma. We suggest that colonoscopic surveillance may be necessary in patients
      with gastric adenoma.

PMID- 19844142
TI  - [Clinical characteristics of intrahepatic cholangiocarcinoma and prognostic
      factors in patients who received non-surgical treatment].
AB  - BACKGROUND/AIMS: This study was conducted to analyze the prognostic factors in
      patients with intrahepatic cholangiocarcinoma (ICC) who did not receive surgery.
      METHODS: Between August 1997 and November 2007, the medical records of 175
      patients (mean age; 66 years, male/female 126/49), who were diagnosed as ICC,
      were reviewed retrospectively. RESULTS: Clonorchiasis and hepatolithiasis was
      found in 14.9%, and 6.3% of all patients, and no risk factors were identified in
      77.8% of them. Surgical resection was performed in 29.1% (51 patients),
      chemotherapy +/- radiotherapy in 12.6% (22 patients), and palliative therapy in
      58.3% (102 patients). The proportion of patients with stage I was 23.4% (41
      patients). The prognostic factors in patients who did not receive surgery were
      alkaline phosphatase (ALP) and bilirubin levels by univariate and multivariate
      analysis. The median survival of patients with normal ALP and bilirubin levels
      was six months, whereas only one month in patients with elevated ALP and
      bilirubin levels (p<0.001). Tumor characteristics of patients with elevated
      bilirubin and ALP levels were infiltrative tumor, bile duct involvement, and very
      huge tumor. CONCLUSIONS: The prognostic factors of ICC in patients who did not
      receive surgery were ALP and bilirubin levels, but not lymph node metastasis.

PMID- 19844143
TI  - [Diagnostic usefulness of PET/CT for pancreatic malignancy].
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the diagnostic
      usefulness of PET/CT for pancreatic malignancy. METHODS: We retrospectively
      analyzed medical records of 115 patients with pathologically diagnosed pancreatic
      cancer between January 2003 to August 2008 who underwent abdominal CT and PET/CT
      examination before histological confirmation. CT and PET/CT images were reviewed
      in single-blinded status and diagnostic ability on primary pancreatic lesion,
      regional lymph node metastasis, and distant metastasis was evaluated. RESULTS: 99
      patients (86%) had malignant diseases including 91 cases of adenocarcinoma, and
      16 patients (14%) benign diseases. Only CA 19-9 value and SUV were significantly
      different between PET/CT positive and negative groups (p=0.001, p<0.001).
      Sensitivity, specificity and positive predictive values (PPV) of both modality
      for pancreatic lesion were same (94%, 62%, and 95%, respectively), and negative
      predictive values (NPV) were 67% on CT and 57% on PET/CT. PET/CT correctly
      diagnosed 8 cases (6.9%) of falsely diagnosed pancreatic lesion on CT. Nine cases
      (15.7%) of misdiagnosed lymph node metastasis on CT were correctly diagnosed on
      PET/CT. But, there was no significant difference in the diagnosis of regional
      lymph node metastasis. 3 out of 29 cases of distant metastasis, except 2 cases of
      supraclavicular lymph node metastasis, were additionally diagnosed by PET/CT.
      But, overall sensitivity of distant metastasis was significantly higher in CT
      (83% vs 69%, p=0.045). CONCLUSIONS: Although PET/CT provided additional correct
      diagnoses in many cases, it showed fair diagnostic power for primary pancreatic
      lesion and lymph node metastasis, and lower sensitivity for distant metastasis.
      Therefore, PET/CT should be used as an supplementary modality of CT in diagnosing
      pancreatic malignancy.

PMID- 19844144
TI  - [A case of liposarcoma arising in the mesentery].
AB  - A liposarcoma is the most common soft tissue sarcoma in adults with an incidence
      of about 20% of all soft tissue sarcomas. Although incidence differs from a
      region of origination, a case arisen from mesentery has rarely been reported. We
      experienced a case of liposarcoma arising from the mesentery of a 51-year-old
      male patient. He was treated by wide excision. Histologically, the tumor was
      composed of a mixed well-differentiated liposarcoma with myxoid and spindle cell
      type.

PMID- 19844145
TI  - [A case of renal vein thrombosis in a patient with ulcerative colitis].
AB  - Venous thrombosis and thromboembolism appear to occur more often in patient with
      inflammatory bowel disease (IBD). The cause of thrombotic complications in IBD is
      generally considered to be associated with hypercoagulable conditions. Its
      prevalence rate ranges from 1% to 8% in clinical studies and rises to 39% in
      autopsy, but the renal vein thrombosis is very rare complication in ulcerative
      colitis patient. A 24-year-old man presented with intermittent abdominal pain and
      hematochezia for 6 months and recently developed pitting edema for few weeks. He
      was diagnosed as severe ulcerative colitis involving whole colon combined with
      thrombosis in both renal veins by colonoscopy and computed tomography scan of
      abdomen. We used steroid for the treatment of ulcerative colitis and both
      intravenous lower molecular weight heparin and warfarin for renal vein
      thrombosis. His symptoms were improved after treatment and maintained with
      mesalazine and warfarin. Follow-up abdominal CT scan showed complete resolution
      of both renal vein thrombosis. Currently he has been followed up for 2 years with
      oral mesalazine.

PMID- 19844146
TI  - [A case of atypical Solid-pseudopapillary tumor of the pancreas].
AB  - Solid-psudopapillary tumor is an uncommon pancreatic neoplasm of low malignant
      potential that most frequently affect young woman. Solid-psudopapillary tumor are
      histologically, clinically, and prognostically quite distinct from the more
      common ductal adenocarcinoma. Recently, we experienced a 36-year-old male who was
      suspected to have extrapancreatic tumor based on atypical radiologic imaging
      study, young age, and male sex, and finally diagnosed as solid-psudopapillary
      tumor on immunohistochemical stain examination. We report this case with review
      of the relevant literatures.

PMID- 19844147
TI  - [Severe acute liver and pancreas damage in anorexia nervosa].
AB  - Anorexia nervosa, a syndrome most commonly affecting young women, is
      characterized by weight less than 85% of weight that is considered normal for
      that persons age and height, distorted body image, and fear of becoming obese,
      and its mortality is up to 9%. We present a case of a 33-year-old woman with a 9
      year history of anorexia nervosa. She admitted to our institution with decreased
      mentality, and her body mass index was 11.5 kg/m2 of the time admission. Initial
      aminotransferase level was severely elevated, but it was normalized solely with
      improved nutrition and weight gain. Five and sixteen days after the admission
      urinary tract infection and elevation of pancreatic enzymes occurred. They were
      successfully treated with antibiotics and nutritional support. Fifty seven days
      after the admission, she discharged. We report a case of acute hepatitis and
      pancreatitis treated with nutritional rehabilitation in a patient with severe
      anorexia nervosa for the first time in Korea.

PMID- 19844148
TI  - [Small bowel obstruction due to enterolith].

PMID- 19844149
TI  - [Hyperdynamic circulation in patients with liver cirrhosis and portal
      hypertension].
AB  - Hyperdynamic circulation in patients with liver cirrhosis is characterized by
      increased cardiac output and heart rate, and decreased systemic vascular
      resistance with low arterial blood pressure and currently focused on
      understanding the pathogenesis because of possibility of developing novel
      treatment modality. Basically, these hemodynamic alternations arise from portal
      hypertension. Portosystemic collaterals develop to counterbalance the increased
      intrahepatic vascular resistance to portal blood flow and induce an increase in
      venous return to heart. Increased shear stress in vascular endothelial cell
      related high blood flow by portosystemic shunting contributes to this
      upregulation of eNOS resulting in NO overproduction. Additionally, bypassing
      through portosystemic collaterals and escaping degradation of over-produced
      circulating vasodilators in the diseased liver can promote the peripheral
      arterial vasodilation. Vasodilation of the systemic and splanchnic circulations
      lead to a reduced systemic vascular resistance, and increased cardiac output and
      splanchnic blood flow. Furthermore, neurohumoral vasoconstrictive systems
      including systemic nervous system, rennin angiotensin aldosterone system, and
      vasopressin are intensively activated secondary to vasodilation. However,
      hyperdynamic circulation would be more aggravated by the activated
      vasoconstrictive systems. With the progression of the cirrhotic process,
      hyperdynamic alternations can be more profound due to hyporesponsiveness to
      vasoconstrictors and increased shunt formation in conjunction with autonomic
      neuropathy. Eventually, splanchnic arterial vasodilation results in an increase
      portal venous inflow, maintaining the elevated portal venous pressure.
      Hyperdynamic circulation is intimately involved in portal hypertension with liver
      cirrhosis, therefore it is reasonable to have an interest in complete
      understanding of the pathogenesis of hyperdynamic circulation to develop novel
      treatment modality.

PMID- 19844150
TI  - [Clinical significance of bowel wall thickening detected with 64-slice
      multidetector computed tomography].
AB  - BACKGROUND/AIMS: The multidetector computed tomography (MDCT) scanning frequently
      leads to the incidental discovery of bowel wall thickening. The aim of this study
      was to determine the utility of gastroscopy and colonoscopy in the management of
      patients who had incidental discovery of bowel wall thickening on MDCT. METHODS:
      From May 2006 to March 2008, the abdominal MDCT reports of all patients in
      Chungbuk National University Hospital were reviewed. Cases with any bowel
      thickening were selected and then patients who received gastroscopy or
      colonoscopy after abdominal MDCT were re-selected. RESULTS: Gastroscopy revealed
      abnormal findings in 22 (95.7%) out of 23 patients, and 10 patients (43.5%) had
      stomach cancers. Colonoscopy revealed abnormal findings in 35 (85.4%) out of 41
      patients, and 12 patients (29%) had malignant tumors. In the patients who had
      lymph node enlargement (p<0.001), dirty fat infiltration (p=0.025), and irregular
      wall thickening (p<0.001) on MDCT malignancy was observed more frequently.
      CONCLUSIONS: We recommend gastroscopy and colonoscopy to patients who had
      incidentally bowel wall thickening found on MDCT, especially those with lymph
      node enlargement, dirty fat infiltration, and irregular wall thickening.

PMID- 19844151
TI  - [Changes in liver stiffness after acute or chronic liver injury due to viral
      hepatitis--does fibrosis exist after recovery from acute viral hepatitis?].
AB  - BACKGROUND/AIMS: Liver stiffness (LS) measurement by transient elastography can
      estimate the degrees of liver fibrosis in patients with chronic liver disease.
      However, longitudinal data of LS after recovery of acute viral hepatitis are
      still lacking. In the present study, we aimed to evaluate among LS of patients at
      various stages of viral hepatitis and normal control. METHODS: Patients who had
      admitted at Korea University Ansan Hospital between January 2006 and January 2007
      due to acute viral hepatitis and recovered were recruited (group A, n=22). We
      compared the liver biochemistry and LS of group A with those of healthy control
      group (group B, n=23), current acute viral hepatitis group (group C, n=49), and
      chronic viral hepatitis group (group D, n=66). RESULTS: Mean ALT, total
      bilirubin, and LS level of group A were not different from group B (p=0.318,
      p=0.116, p=0.125, respectively). However, group A had lower ALT, total bilirubin,
      and LS values compared to group C (all p<0.001), and lower ALT and LS values
      compared to group D (p=0.007, p<0.001). The mean total bilirubin was not
      significantly different from group D (p=0.117). CONCLUSIONS: Our data suggest
      that liver fibrosis is a long-term sequela of chronic hepatitis, and not
      developed in patients who recovered from acute viral hepatitis.

PMID- 19844152
TI  - [Extrapancreatic tumors in intraductal papillary mucinous neoplasm of the
      pancreas].
AB  - BACKGROUND/AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas
      has a favorable prognosis, but seems to be associated with a high incidence of
      extrapancreatic tumors. The purpose of this study was to evaluate the incidence
      and clinicopathological features of extrapancreatic tumors associated with IPMN.
      METHODS: Thirty-seven patients with IPMN of the pancreas, confirmed by surgical
      resection and typical findings of endoscopic ultrasonography and CT imaging
      between October 1, 1998 and August 31, 2006 were included. Seventeen patients
      were diagnosed with surgical resection and biopsy, and others by typical imaging
      findings of IPMN. These patients were examined for the development of
      extrapancreatic tumors. RESULTS: Of 37 patients with IPMN, 14 (38%) had 18
      extrapancreatic tumors, and 10 (27%) had 13 extrapancreatic malignancies. Five,
      six, and two extrapancreatic malignancies had been diagnosed before, during, and
      after the diagnosis of IPMN. Gastric adenocarcinoma (3 patients, 23%) and
      colorectal carcinoma (3 patients, 23%) were the most common neoplasms. Other
      extrapancreatic tumors included lung cancer (n=2), prostatic cancer (n=1), renal
      cell carcinoma (n=1), cholangiocellular carcinoma (n=1), urinary bladder cancer
      (n=1), and gallbladder cancer (n=1), respectively. As benign tumor, there were
      two gallbladder adenoma, one gastric adenoma, one colonic adenoma and one benign
      ovarian cystic neoplasm, respectively. CONCLUSIONS: IPMN is associated with high
      incidence of extrapancreatic tumors, particularly gastric and colorectal
      neoplasms. Upper gastrointestinal endoscopy and colonoscopy should be done, and
      systemic surveillance for the possible occurrence of other tumors may allow early
      detection of extrapancreatic tumor in patients with IPMN.

PMID- 19844153
TI  - [Prevalence of pancreatic cancer in diabetics and clinical characteristics of
      diabetes-associated with pancreatic cancer--comparison between diabetes with and
      without pancreatic cancer].
AB  - BACKGROUND/AIMS: In Korea, the prevalence of pancreatic cancer (PC) in general
      population has been reported as 7 in 100,000. However, that in diabetes mellitus
      (DM) has not been elucidated yet. This study was designed to estimate the
      prevalence of PC among DM patients, and characterize and compare the patients
      with DM with and without PC. METHODS: 5,082 patients (4,890 DM without PC, 78 PC
      with DM, and 114 PC without DM) were enrolled from Korea University Guro Hospital
      during a period of 4 years between January 2004 and January 2008. RESULTS: The
      prevalence of PC in DM patients was 1.6% and that of DM in PC patients was 40.6%.
      No significant differences in the clinical characteristics except HbAIc and ALP
      were observed between PC patients with DM and without DM. Among 78 PC patients
      with DM, DM was diagnosed in 19 (29.4%) and 29 (37.1%) patients concomitantly or
      within 2 years prior to the diagnosis of PC, respectively. Among the cases with
      recent onset DM (less than 2 years duration), the disease duration of DM before
      the diagnosis of PC was less than 1 year in 14 patients (17.9%) and 1 to 2 years
      in 15 patients (19.2%). DM patients with PC were found to have significantly
      higher ALT, total bilirubin, and ALP levels than in DM patients without PC.
      CONCLUSIONS: The prevalence of PC in DM patients was 1.6% and was higher than in
      the general population. Recent onset DM was frequent in PC patients (less than 2
      years duration). We recommend close follow-up for at least 2 years in new-onset
      diabetes.

PMID- 19844154
TI  - [A case of CD56+ extranodal NK/T-cell lymphoma, nasal type, presenting as a
      duodenal ulcer bleeding].
AB  - Extranodal NK/T-cell lymphoma is a recently recognized distinct entity within the
      World Health Organization classification of lymphoid tumors. It is relatively
      prevalent in Asian and South American populations. It most commonly occurs in the
      nasal or paranasal areas and less frequently in the skin, the soft tissue, and
      the gastrointestinal tract. Among these, extranodal NK/T-cell lymphoma of the
      gastrointestinal tract has shown an aggressive clinical course. We report a case
      of CD56+ extranodal NK/T-cell lymphoma presenting as a duodenal ulcer bleeding. A
      62-year-old male patient presented with melena and abdominal pain. Endoscopic
      examination of the upper gastrointestinal tract showed the duodenal ulcer covered
      by blood clot. Pathologic examination revealed the diffuse infiltration of
      atypical lymphocytes with an angiocentric growth pattern, which was positive for
      CD3, CD56, and granzyme. The patient showed rapid deteriorating clinical course
      and died on day 14 after admission. Thus, we report this case with the review of
      literatures.

PMID- 19844155
TI  - [Two cases of colonic obstruction after acute pancreatitis].
AB  - Several forms of colonic complications are rarely observed during the clinical
      course of acute pancreatitis, and potentially fatal in some cases. Colonic
      lesions associated with acute pancreatitis can be divided into several groups
      from a pathogenic point of view. Possible pathogenesis includes: 1) spread of
      pancreatic enzymes through the retroperitoneum to mesocolon, causing pericolitis,
      2) external inflammatory compression by mesocolic mass secondary to necrosis of
      fatty tissue, and 3) hypotension due to shock, and thrombosis of mesenteric
      arteries. These might lead to colonic infarction, fistula formation, perforation,
      and obstruction during follow-up. We report two cases of colonic obstruction
      following acute pancreatitis with possible different mechanisms and review Korean
      cases. One patient developed colonic obstruction due to severe necrotizing
      pancreatitis, possibly as a result of pericolitis, and the other developed
      stenosis as a result of ischemic colitis induced by acute pancreatitis.

PMID- 19844156
TI  - [Small cell carcinoma of extrahepatic bile duct presenting with hemobilia].
AB  - We report a case of small cell carcinoma of extrahepatic bile duct presenting
      with jaundice and hemobilia. A 59-year-old woman was admitted due to right upper
      quadrant pain and jaundice. An abdominal computed tomography revealed a 2 cm
      sized mass in the extrahepatic bile duct. Endoscopic retrograde
      cholangiopancreatography revealed bloody discharge coming out of the papillary
      orifice in endoscopic view and a dilated extrahepatic bile duct with multiple
      irregular filling defects in cholangiogram. A coronal T2-weighted image revealed
      a hyperintense mass at extrahepatic bile duct. Laparotomy was performed, and
      pathologic examination of resected specimen showed tumor cells having round to
      oval nuclei with coarsely granular chromatin and scanty cytoplasm, which were
      immunoreactive for synaptophysin and chromogranin A, compatible with the
      diagnosis of small cell carcinoma. The small cell carcinoma of bile duct, despite
      its rarity, should be considered in differential diagnosis of the causes for
      obstructive jaundice and hemobilia.

PMID- 19844157
TI  - [A case of primary biliary malignant lymphoma mimicking Klatskin tumor].
AB  - Primary non-Hodgkin's lymphoma of the extrahepatic bile duct presenting as
      obstructive jaundice is extremely rare. A 60-year-old man was admitted due to
      suddenly developed jaundice. Computerized tomography and endoscopic retrograde
      cholangiopancreatography showed a tumor at the proximal common hepatic duct.
      These clinical and radiologic findings resembled those of Klatskin tumor. The
      resection of the common hepatic duct tumor, lymph node dissection, and Roux-en-Y
      hepaticojejunostomy were carried out. There was no regional lymph node metastasis
      and no residual tumor at the resection margins. Histology and
      immunohistochemistry of the resected specimen confirmed a diffuse large B-cell
      malignant lymphoma involving the common hepatic duct. The patient is scheduled to
      receive adjuvant chemotherapy. In summary, primary non-Hodgkins lymphoma of the
      extrahepatic bile duct, despite its rarity, should be considered in the
      differential diagnosis of causes for obstructive jaundice. An accurate
      histopathologic diagnosis and surgical resection combined with chemotherapy may
      be the approach to offer a chance for cure.

PMID- 19844158
TI  - [Meaning of incidence of extrapancreatic neoplasms in patients with intraductal
      papillary mucinous neoplasms of pancreas].

PMID- 19844160
TI  - Autophagy proteins promote hepatitis C virus replication.
AB  - Autophagy is a fundamental process for anti-viral defense. Not surprisingly,
      viruses have developed strategies to subvert or use autophagy for their own
      benefit. In cell culture, autophagy proteins are proviral factors that favor
      initiation of hepatitis C virus (HCV) infection. Autophagy proteins are required
      for translation of incoming viral RNA. We propose that autophagy factors might
      support the delivery of incoming RNA to the translation apparatus and/or the
      recruitment of cellular factors required to initiate HCV translation.

PMID- 19844159
TI  - Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a
      cellular model and in mice.
AB  - Mammalian white adipocytes have a unique structure in which nearly the entire
      cell volume is occupied by a single large lipid droplet, while the surrounding
      cytoplasm occupies minimal space. The massive cytoplasmic remodeling processes
      involved in the formation of this unique cellular structure are poorly defined.
      Autophagy is a membrane trafficking process leading to lysosomal degradation of
      cytoplasmic components. Here, we investigated the functional role of atg5, a gene
      encoding an essential protein required for autophagy, in adipocyte
      differentiation in a cellular model and in mice. Massive autophagy was activated
      when wild-type primary mouse embryonic fibroblasts (MEFs) were induced for
      adipocyte differentiation. Importantly, the autophagy deficient primary atg5(-/-)
      MEFs exhibited dramatically reduced efficiency in adipogenesis. Time-lapse
      microscopy revealed that atg5(-/-) MEFs initially appeared to differentiate
      normally; however, a majority of the differentiating atg5(-/-) cells ultimately
      failed to undergo further morphological transformation and eventually died,
      likely through apoptosis. Consistent with these in vitro results, histological
      analysis revealed that the atg5(-/-) late-stage embryos and neonatal pups had
      much less subcutaneous perilipin A-positive adipocytes. Consistently, when
      treated with chloroquine, a functional inhibitor of autophagy, wild-type MEFs
      exhibited drastically reduced efficiency of adipocyte differentiation. Taken
      together, these findings demonstrated that Atg5 is involved in normal adipocyte
      differentiation, suggesting an important role of autophagy in adipogenesis.

PMID- 19844162
TI  - Cell nonhomologous end joining capacity controls SAF-A phosphorylation by DNA-PK
      in response to DNA double-strand breaks inducers.
AB  - Aiming to identify novel phosphorylation sites in response to DNA double-strand
      breaks (DSB) inducers, we have isolated a phosphorylation site on KU70.
      Unexpectedly, a rabbit antiserum raised against this site cross-reacted with a
      120 kDa protein in cells treated by DNA DSB inducers. We identified this protein
      as SAF-A/hnRNP U, an abundant and essential nuclear protein containing regions
      binding DNA or RNA. The phosphorylation site was mapped at S59 position in a
      sequence context favoring a "S-hydrophobic" consensus model for DNA-PK
      phosphorylation site in vivo. This site was exclusively phosphorylated by DNA-PK
      in response to DNA DSB inducers. In addition, the extent and duration of this
      phosphorylation was in inverse correlation with the capacity of the cells to
      repair DSB by Nonhomologous End Joining. These results bring a new link between
      the hnRNP family and the DNA damage response. Addtionaly, the mapped phospho-site
      on SAF-A might serve as a potential bio-marker for DNA-PK activity in academic
      studies and clinical analyses of DNA-PK activators or inhibitors.

PMID- 19844161
TI  - Basal autophagy induction without AMP-activated protein kinase under low glucose
      conditions.
AB  - When ATP levels in a cell decrease, various homeostatic intracellular mechanisms
      initiate attempts to restore ATP levels. As a prominent energy sensor, AMP
      activated protein kinase (AMPK) represents one molecular gauge that links energy
      levels to regulation of anabolic and catabolic processes to restore energy
      balance. Although pharmacological studies have suggested that an AMPK activator,
      AIC AR (5-aminoimidazole-4-carboxamide ribonucleoside) may link AMPK activation
      to autophagy, a process that can provide short-term energy within the cell, AICAR
      can have AMPK-independent effects. Therefore, using a genetic-based approach we
      investigated the role of AMPK in cellular energy balance. We demonstrate that
      genetically altered cells, mouse embryonic fibroblasts (MEFs), lacking functional
      AMPK, display altered energy balance under basal conditions and die prematurely
      under low glucose-serum starvation challenge. These AMPK mutant cells appear to
      be abnormally reliant on autophagy under low glucose basal conditions, and
      therefore cannot rely further on autophagy like wild-type cells during further
      energetic stress and instead undergo apoptosis. This data suggests that AMPK
      helps regulate basal energy levels under low glucose. Further, AMPK mutant cells
      show increased basal phosphorylation of p53 at serine 15, a residue
      phosphorylated under glucose deprivation. We propose that cells lacking AMPK
      function have altered p53 activity that may help sensitize these cells to
      apoptosis under energetic stress.

PMID- 19844163
TI  - Genetic manipulations reveal dynamic cell and gene functions: Cre-ating a new
      view of myogenesis.
AB  - Development of multicellular organisms is temporally and spatially complex. The
      Cre/loxP and Flp/FRT systems for genetic manipulation in mammals now enable
      researchers to explicitly examine in vivo the temporal and spatial role of cells
      and genes during development via cell lineage and ablation studies and
      conditional gene inactivation and activation. Recently we have used these methods
      to genetically dissect the role of Pax3(+) and Pax7(+) progenitor populations and
      the function of beta-catenin, an important regulator of myogenesis, in vertebrate
      limb myogenesis. Our lineage and ablation studies of Pax3(+) and Pax7(+)
      progenitors revealed surprising insights into myogenesis not apparent from Pax3
      and Pax7 expression and functional studies. In addition, conditional inactivation
      and activation of beta-catenin in different progenitor populations and their
      progeny demonstrated that beta-catenin plays several cell-autonomous roles in
      myogenesis. Our studies highlight the hierarchical (i.e., genes versus cells),
      temporal and spatial complexity of development and demonstrate that manipulations
      of both cells and genes will be required to obtain a full understanding of the
      development of multicellular organisms.

PMID- 19844164
TI  - Regulation of p53: TRIM24 enters the RING.
AB  - Negative regulation of p53 in normal, unstressed cells maintains levels of this
      tumor suppressor below a threshold for cell cycle arrest or apoptosis, and is
      rapidly reversed in the face of cellular stresses to permit p53 response.
      Recently, we created a new mouse and stem cell model by knock-in addition of an
      epitope tag at Trp53. Biochemical purification of endogenous, tagged p53-protein
      complexes from mouse embryonic stem cells, and peptide analysis by mass
      spectrometry, revealed a new RING-domain E3-ubiquitin ligase TRIM24 that targets
      p53 for degradation. Depletion of TRIM24, formerly named TIF1alpha, in tumor
      derived cells induces p53-dependent apoptosis. In Drosophila, bonus is a single
      copy gene homologous to the mammalian Tif1 family. Mosaic deletion of bonus
      induces cell death in vivo, which is rescued by depletion of D-p53. Bonus is the
      first identified regulator of p53 protein levels in Drosophila, which lacks an
      ortholog of Mdm2. TRIM24/bonus may be the ancestral precursor of the large group
      of mammalian E3-ligases that target p53 for ubiquitin modification. Understanding
      the specific roles that these numerous E3-ligases have in the hierarchy of p53
      regulation remains a challenge for the field. We discuss various scenarios for
      selectivity in choice of E3-ligase targeting p53 for degradation.

PMID- 19844165
TI  - Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer
      regulated.
AB  - Functional expression of KAL1 gene is critical in the migration of GnRH neurons
      from the olfactory placode to the hypothalamus in embryogenesis. This gene thus
      far has not been shown to play a functional role in any other physiological or
      pathological process either in the developed brain or in peripheral tissues. We
      show here that KAL1 gene expression is decreased in early stage and increased in
      later stages of cancers. Screening of colon, lung and ovarian cancer cDNA panels
      indicated significant decrease in KAL1 expression in comparison to corresponding
      uninvolved tissues. However, KAL1 expression increased with the progression of
      cancer from early (I and II) stages to later (III and IV) stages of the cancer.
      There was a direct correlation between the TGFbeta and KAL1 expression in colon
      cancer cDNA. Using colon cancer cell lines, we showed that TGFbeta induces KAL1
      gene expression and secretion of anosmin-1 protein (KAL1 coded protein). We
      further report that hypoxia induces anosmin-1 expression; anosmin-1 protects
      cancer cells from apoptosis activated by hypoxia and increases cancer cell
      mobility. Using siRNA technique we found that KAL1 expression following hypoxia
      is hypoxia-inducible factor (HIF-1)alpha dependent. Our results suggest that KAL1
      gene expression plays an important role in cancer metastasis and protection from
      apoptosis.

PMID- 19844166
TI  - Insights into the function of the human P-TEFb component CDK9 in the regulation
      of chromatin modifications and co-transcriptional mRNA processing.
AB  - Cyclin-dependent kinase-9 (CDK9) was originally characterized as a transcription
      elongation factor which regulates RNA Polymerase II (RNAPII) activity following
      transcriptional initiation. However, recent evidence from a number of studies
      have shown that CDK9 plays an important role in regulating not only RNAPII
      activity but also co-transcriptional histone modification and mRNA processing
      events such as splicing and 3' end processing. Importantly, our previous work and
      the work presented here demonstrate that CDK9 functions to guide a complex
      network of chromatin modifications including histone H2B monoubiquitination
      (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3. This function
      appears to be dependent upon not only the phosphorylation of the RNA Polymerase
      II C-terminal domain but also upon other CDK9 targets such as the Suppressor of
      Ty Homolog-5 (SUPT5H), Negative Elongation Factor-E (NELF-E) and probably the
      human Rad6 homolog UBE2A. We provide a working model by which CDK9 may control co
      transcriptional replication-dependent histone mRNA 3' end processing in an H2Bub1
      and H3K4me3-dependent manner and uncover new and important differences between
      the functions of human CDK9 and its yeast counterparts Ctk1 and Bur1.

PMID- 19844167
TI  - Systematically linking drug susceptibility to cancer genome aberrations.
AB  - Genetic aberrations (lesions) govern the transformation of previously normal
      cells into cancer cells by changing key signaling pathways within the cells that
      control cellular proliferation, differentiation and survival. Such lesions are
      thus considered prime molecular targets for cancer therapy. While some notable
      examples underscore the clinical relevance of this connection between genetics
      and drug response, there is a lack of analytical approaches to provide such novel
      "drug-mutation" combinations in a broad and unbiased fashion. We have therefore
      collected a panel of genetically and phenotypically characterized nonsmall cell
      lung cancer (NSCLC) cell lines to systematically screen for drug susceptibility
      of NSCLC as a function of genetic lesions. We found such genetic lesions to
      predict activity of geldanamycin-derived Hsp90 inhibitors as well as of the
      clinically approved SRC/ABL-inhibitor dasatinib. This work may therefore help
      advancing our understanding of critical oncogenic pathway dependencies and may
      impact future drug development by defining drug-susceptible patient populations.

PMID- 19844168
TI  - AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor.
AB  - The AMP-activated protein kinase (AMPK) system, an evolutionary conserved low
      energy checkpoint, functions as a canonical suppressor of cell proliferation.
      Proliferating cells, however, should also ensure a proper spatio-temporal bond
      between AMPK-sensed cell's metabolic status and cell division. A crucial linkage
      between cell proliferation and AMPK-interpreted cell bioenergetics appears to
      take place during the M-phase of the cell cycle. A recent description of a
      physical interplay between the active form the alpha-catalytic AMPK subunit with
      essential mitotic regulators in the centrosome and midbody has provided direct
      evidence that tumor-suppressive properties for AMPK closely relate to its ability
      to exquisitely coordinate sensing of energy resources and the fundamental
      biological process of genome division during mitosis and cytokinesis. Based on
      recent findings in our laboratory observing abortive cytokinesis followed by
      nuclear shape reorganization, mitotic catastrophe, polyploidization events, and
      cell giantism in p53-null cancer cells pharmacologically manipulated to exhibit
      sustained activation of AMPK, we now propose that AMPK is a novel and
      biologically significant participant with a tumor suppressive activity in the
      mitotic/cytokinetic phase of the cell cycle. In this scenario, molecular co
      evolution of the energy-sensing cytokinetic tumor suppressor AMPK within the
      chronic biophysical constraints of the tumor microenvironment may inherently
      promote a continuous generation of structural and numerical changes in
      chromosomes favoring generation of nascent tumor cells and/or tumor-initiating
      cells over tumor cell death.

PMID- 19844169
TI  - A theoretical model for p53 dynamics: identifying optimal therapeutic strategy
      for its activation and stabilization.
AB  - The activation and stabilization of tumor suppressor p53 are very important in
      preventing cells from becoming cancerous. Hence, many experimental works have
      been carried out to investigate p53's dynamics through its interactions with
      other proteins and its therapeutic applications for the treatment of cancers. In
      this work, by analyzing a theoretical model, we attempt to search for an optimal
      therapeutic strategy that guarantees the activation and stabilization of p53. For
      this purpose, we introduce a new mathematical model including oncogene activation
      and ARF, which are recognized as crucial for tumor suppression but have not yet
      been considered in most theoretical works. Through mathematical modeling and
      numerical simulations, we confirm several important properties of p53 dynamics:
      the role of the oncogene-mediated activation of ARF as an important factor for
      the activation and stabilization of p53, the necessity of time delays in negative
      feedback loops to guarantee sustained p53 oscillations, and the digital behavior
      of p53 pulses. Furthermore, we propose that the binding of ARF to Mdm2 and
      enhancing the degradation of Mdm2 is an efficient strategy for therapeutic
      targeting, which may assure the activation and stabilization of p53.

PMID- 19844171
TI  - Geometric control of the cell cycle.
AB  - How do cells sense their own size and shape? And how does this information
      regulate progression of the cell cycle? Our group, in parallel to that of Paul
      Nurse, have recently demonstrated that fission yeast cells use a novel geometry
      sensing mechanism to couple cell length perception with entry into mitosis. These
      rod-shaped cells measure their own length by using a medially-placed sensor,
      Cdr2, that reads a protein gradient emanating from cell tips, Pom1, to control
      entry into mitosis. Budding yeast cells use a similar molecular sensor to delay
      entry into mitosis in response to defects in bud morphogenesis. Metazoan cells
      also modulate cell proliferation in response to their own shape by sensing
      tension. Here I discuss the recent results obtained for the fission yeast system
      and compare them to the strategies used by these other organisms to perceive
      their own morphology.

PMID- 19844170
TI  - Protective roles of matrix metalloproteinases: from mouse models to human cancer.
AB  - Matrix metalloproteinases (MMPs) have long been linked to cancer progression
      owing to their ability to breakdown tissue barriers for metastatic spread.
      Accordingly, multiple studies have examined the potential value of these enzymes
      as targets for cancer therapy. Unfortunately, most clinical trials with MMP
      inhibitors have yielded negative results which has made necessary to re-evaluate
      the role of these proteases in cancer. Recent works mainly based on the use of
      mouse models deficient in specific MMPs have revealed that these enzymes play
      many roles in cancer distinct from matrix destruction, influencing early steps of
      tumor evolution, and expanding their pro-tumorigenic properties. However, these
      in vivo studies have also shown that, unexpectedly, some MMP family members like
      MMP8 may have paradoxical anti-tumor functions. Nevertheless, the final
      validation of these MMPs as bona fide tumor suppressors requested the
      identification of the putative genetic or epigenetic changes underlying their
      inactivation during cancer development. To this purpose, very recent large-scale
      genomic studies have explored the possibility that MMPs could be genetically
      altered in a panel of human malignant tumors from different sources. These
      studies have demonstrated that MMP8 is a frequently mutated gene in human
      melanoma. Functional analysis of the identified mutations has confirmed that all
      of them lead to the loss-of-function of MMP8 and enhance the progression of
      melanoma, thus providing definitive evidence that MMP8 is a tumor-suppressor
      gene. Parallel studies have extended these findings to other MMP-related
      metalloproteinases such as ADAMTS15, which has been found to be genetically
      inactivated in human colorectal cancer. This review describes the identification
      and validation of some MMPs and related enzymes as anti-tumor proteases and
      speculates about the molecular mechanisms underlying their protective roles in
      tumor development. Finally, the review explores the clinical applications derived
      from the identification of MMPs that favour the host instead of the tumor.

PMID- 19844172
TI  - Musings on matters medical-legal: a missive in remembrance of A. Bernard
      Ackerman, MD.

PMID- 19844174
TI  - Asymptomatic nodule's on a child's back: Challenge. Fibrous hamartoma of infancy.

PMID- 19844175
TI  - Carbon monoxide releasing molecule-2 decreases thick diameter fibrin fibre
      formation in normal and Factor XIII deficient plasmas.
AB  - Carbon monoxide derived from carbon monoxide releasing molecules (CORMs) has been
      demonstrated to enhance normal plasma thrombus speed of growth and strength as
      well as diminish vulnerability to fibrinolysis in vitro. We tested the hypothesis
      that tricarbonyldichlororuthenium (II) dimer (CORM-2) would modify plasma thrombi
      ultrastructure as determined by electron microscopy. Normal and FXIII-deficient
      (<1% normal activity) plasmas were exposed to 0 or 100 micromol/l CORM-2, with
      coagulation initiated with tissue factor followed by a 15 min incubation at 37
      degrees C prior to fixation. Transmission electron microscopy of the four
      conditions was conducted at 5000-60,000-fold magnification. CORM-2 markedly
      diminished the formation of thick diameter fibrin fibres in normal plasma and
      FXIII-deficient plasma. The density of thin diameter fibrin fibres did not seem
      to be changed by CORM-2 in normal plasma, but was increased in FXIII-deficient
      plasma. CORM-2 significantly modifies thrombin-mediated polymerization of fibrin.
      This finding may partially explain how CORM-2 exposure results in stronger
      thrombi resistant to fibrinolysis.

PMID- 19844176
TI  - Low-molecular-weight heparin and unfractionated heparin in prophylaxis against
      deep vein thrombosis in critically ill patients undergoing major surgery.
AB  - The objective of the present study was to compare the efficacy and safety of low
      dose unfractionated heparin (UFH) and a low-molecular-weight heparin (LMWH) as
      prophylaxis against venous thromboembolism in critically ill surgical patients
      undergoing major surgery. This was a randomized prospective study in which
      critically ill patients scheduled to undergo major elective surgery were
      allocated to receive subcutaneously either LMWH once daily and a placebo
      injection containing sterile 0.9% normal saline or 5000 IU UFH twice daily
      subcutaneously. Each patient was evaluated postoperatively clinically and
      confirmed by Doppler study for development of deep vein thrombosis (DVT). One
      hundred and fifty-six patients completed the protocol. There was similar efficacy
      of UFH as compared with LMWH in the prophylaxis of DVT. There was also no
      statistically significant difference in the incidence of major complications in
      the heparin group as compared with the LMWH group. However, minor hemorrhagic
      complications such as wound hematoma and surgical site bleeding were
      significantly more in the heparin group as compared with the LMWH group. Both UFH
      5000 units subcutaneously twice daily and LMWH 40 mg once daily provide highly
      effective and well tolerated prophylaxis for critically ill surgical patients.
      Considering the advantage of once-daily dosing, a wider adoption of prophylaxis
      with LMWH may be justified on the basis of patient acceptability and saving of
      nursing time.

PMID- 19844177
TI  - An update on robotic thoracic surgery and anesthesia.
AB  - PURPOSE OF REVIEW: Minimally invasive surgery involving the thoracic cavity
      continues to increase. With the introduction of robotic systems, particularly the
      da Vinci robot system more than 10 years ago, thoracic operations have been
      performed with some provocative results and limited, defined advantages. The
      present review provides an overview of common thoracic surgical procedures
      performed with the robotic system and discusses the anesthetic implications.
      RECENT FINDINGS: The literature on this topic currently includes case reports or
      series of clinically prospective or retrospective observational reports with the
      use of robotic systems, involving the thoracic cavity (mediastinal mass
      resections, lobectomies, and esophagectomies); unfortunately there are very
      limited reports related to anesthetic implications or complications related to
      the use of this technology. The majority of the surgical reports involve the use
      of lung isolation devices for thoracic surgery, specifically the use of a double
      lumen endotracheal tube (DLT); a few centers use carbon dioxide (CO2)
      insufflation as part of their management to achieve maximal surgical exposure
      while compressing the operative side of the lung away from the operative area.
      SUMMARY: Anesthesiologists must be familiar with lung isolation techniques and
      flexible fiberoptic bronchoscopy while participating in thoracic surgical cases
      that require robotic systems. In addition, prevention and recognition of
      potential complications, such as crushing injuries or nerve damage, must be
      sought. Because the potential for converting to an open thoracotomy exists, all
      measures must be taken to manage patients accordingly if the situation arises.

PMID- 19844178
TI  - Peripheral venous pressure waveform.
AB  - PURPOSE OF REVIEW: The focus of intraoperative monitoring is moving away from
      invasive monitoring. This has been attributed to procedure time, cost, and the
      known risks, which include carotid artery puncture, arrhythmia, pneumothorax, and
      infection. Until recently, the venous system's contribution to the circulatory
      system has been incorrectly identified as being insignificant. This article
      summarizes the unique characteristics of the peripheral venous system. RECENT
      FINDINGS: Numerous studies done in the last few years have paid attention to
      peripheral venous pressure and more specifically its pressure waveform. The
      popularity of, and further focus on, the field of photoplethysmography has
      described a strong venous component. Analysis of venous waveforms has indicated
      that, like arterial waveforms, they too exhibit respiratory variations and change
      in response to physiologic challenges. SUMMARY: The veins play a critical role in
      cardiovascular homeostasis; they do more than conduct blood to the heart.
      Considering the ease of measurement from a peripheral intravenous catheter,
      further study should be conducted to investigate the usefulness and limitations
      of such a minimally invasive and inexpensive monitoring device.

PMID- 19844179
TI  - Recombinant human thyroid-stimulating hormone as an alternative for thyroid
      hormone withdrawal in thyroid cancer management.
AB  - PURPOSE OF REVIEW: The purpose of the review is to summarize the current findings
      of using recombinant human thyroid-stimulating hormone (rhTSH, also known as
      Thyrogen) as adjuvant stimulation for diagnostic monitoring, thyroid remnant
      ablation, and treatment of metastatic thyroid cancer. RECENT FINDINGS: A negative
      Thyrogen-stimulated thyroglobulin level has a negative predictive value of up to
      98.5%. Therefore, it is unnecessary to repeat a Thyrogen-stimulated thyroglobulin
      level in the surveillance of patients with a negative result. There are no
      significant differences found in the rate of recurrence or persistent disease
      between Thyrogen-assisted and thyroid hormone withdrawal-ablated patient groups.
      Studies have shown that rapid clearance of excess radioiodine from the body in
      the euthyroid state with Thyrogen stimulation has significantly reduced whole
      body radiation exposure as compared with the hypothyroid state in withdrawal
      patients. SUMMARY: Thyrogen-assisted diagnosis and radioiodine ablation of
      thyroid remnant provide a reliable tool in the management of thyroid cancer
      without sacrificing patient quality of life. We believe that the use of Thyrogen
      for radioiodine treatment of metastatic thyroid cancer may also provide a better
      option due to its rapid preparation time and safety. Further prospective studies
      are required for the assessment of long-term outcomes.

PMID- 19844180
TI  - Primary thyroid lymphoma: a review of recent developments in diagnosis and
      histology-driven treatment.
AB  - PURPOSE OF REVIEW: Primary thyroid lymphoma (PTL) is a rare but clinically
      important malignancy of the thyroid. This article reviews the diagnosis,
      histologic subtypes, pathogenesis, and treatment of PTL, with the objective of
      optimizing diagnosis and management of the disease. RECENT FINDINGS: Recent
      studies have shed light on the clinicopathologic features of the histologic
      subtypes of PTL. Analysis of the pathogenesis of PTL indicates that both
      antigenic stimulation in the setting of Hashimoto's thyroiditis and aberrant
      somatic hypermutation may play a role. The first large, population-based study of
      PTL indicated that age, stage, histologic subtype, and treatment modality have
      prognostic implications. The U.S. Food and Drug Administration approval of
      rituximab for non-Hodgkin's lymphoma has improved standard chemotherapeutic
      options, as data on efficacy in nodal and other extranodal lymphomas have been
      extrapolated to PTL. SUMMARY: Advances in the understanding of the histologic
      subtypes of PTL have led to more accurate diagnosis and tailored treatments. The
      introduction of a new chemotherapeutic agent has expanded the treatment paradigm
      for PTL. Important prognostic indicators of survival for patients with PTL have
      been confirmed in the first population-based study. This article emphasizes
      current diagnostic and treatment approaches and discusses the potential for
      future developments.

PMID- 19844181
TI  - Asthma in the elderly: current knowledge and future directions.
AB  - PURPOSE OF REVIEW: Asthma is a common disease in the older population that is
      frequently undiagnosed and undertreated. We will review the current knowledge of
      asthma in the elderly (AIE) and shed light on the diagnostic and management
      challenges outlining needs for future research. RECENT FINDINGS: There has been
      very little original research in the field of AIE published in the last few
      years, and current literature focuses primarily on a series of review articles.
      AIE often presents with multiple comorbidities, which complicates its course and
      management. There is renewed interest in nonallergic (intrinsic) asthma. T helper
      cell 1 inflammation triggered by respiratory infection, superantigens, proteases
      and interleukin 17 are possible mechanisms. An association between systemic
      inflammation in frailty and asthma may also be important. SUMMARY: The diagnosis
      and treatment of AIE requires that the individual patient and his or her specific
      triggers and the likely pathophysiology be understood. Understanding the
      mechanisms of inflammation in this population is key to improved therapeutic
      interventions.

PMID- 19844182
TI  - Recent insight into obesity and asthma.
AB  - PURPOSE OF REVIEW: The worldwide pandemic of obesity is creating unique
      challenges for the diagnosis and treatment of asthma. A wealth of epidemiologic
      literature has established that whereas asthma can lead to obesity, obesity is a
      risk factor for asthma, but mechanisms are unclear. This review assesses the
      current understanding of the relationship between obesity and asthma. RECENT
      FINDINGS: Recent studies are developing a more sophisticated understanding of the
      possible inflammatory, immunologic, genetic, and mechanical mechanisms underlying
      the association between obesity and asthma. Obese asthma may be a unique
      phenotype of asthma, with a more difficult clinical course and altered response
      to asthma controller therapy. Adipokines such as leptin and adiponectin are
      thought to be important, but there is new interest in other inflammatory
      mechanisms related to visceral obesity, insulin resistance, and the metabolic
      syndrome. SUMMARY: There are still far more questions than answers as to how
      obesity might cause or worsen asthma. It is clear that weight gain and obesity
      are particularly troublesome in asthmatics, and clinicians should target these
      individuals for aggressive intervention. Randomized controlled trials are needed
      to determine the best treatment approaches for obese asthma, and prospective
      studies in which both obesity and asthma are well characterized are needed to
      better understand the underlying mechanisms.

PMID- 19844183
TI  - Frequency of gastroenteritis and gastroenteritis-associated mortality with early
      weaning in HIV-1-uninfected children born to HIV-infected women in Malawi.
AB  - BACKGROUND: We assessed gastroenteritis (GE) burden in 2 randomized trials
      conducted in Malawi to reduce postnatal HIV transmission before and after World
      Health Organization recommendations regarding exclusive breastfeeding for HIV
      exposed infants were adopted. The 2 trials were the nevirapine/AZT (NVAZ, 2000
      2003 with prolonged breastfeeding) and the Postexposure Prophylaxis to the Infant
      (PEPI, 2004-2007 with breastfeeding cessation by 6 months). METHODS: From NVAZ
      and PEPI trials data, GE frequency through age 12 months among HIV-negative
      exposed infants was evaluated. Overall and GE-related cumulative mortality rates
      were estimated using Kaplan-Meier curves. RESULTS: The frequency of at least one
      GE-related hospitalization was greater in PEPI vs. NVAZ after age 6 months
      (respectively, 2.9% vs. 0.1%, at 7-9 months and 1.6% vs. 0.2% at 10-12 months, P
      < 0.001). Cumulative GE-related mortality was significantly higher in PEPI than
      in NVAZ after age 6 months; at ages 9 and 12 months GE-related mortality was 19
      and 24 per 1000 infants in PEPI vs. 7 and 12 per 1000 infants in NVAZ (P =
      0.0002). CONCLUSIONS: Early weaning was associated with increased risk of severe
      GE and GE-related mortality among HIV-exposed infants. Strategies are urgently
      needed which allow longer breastfeeding while reducing the risk of HIV breast
      milk transmission in resource-limited settings.

PMID- 19844185
TI  - Impact of hypertension on left ventricular structure in patients with
      asymptomatic aortic valve stenosis (a SEAS substudy).
AB  - OBJECTIVE: Both hypertension and aortic valve stenosis induce left ventricular
      hypertrophy. However, less is known about the influence of concomitant
      hypertension on left ventricular structure in patients with aortic valve
      stenosis. METHODS: Baseline Doppler echocardiography was performed in 1720
      patients with asymptomatic aortic valve stenosis (peak transaortic velocity
      >or=2.5 m/s and <or=4.0 m/s) recruited in the Simvastatin and Ezetimibe in Aortic
      Stenosis study at 173 centers in seven European countries. Patients were grouped
      as normotensive (n = 482) or hypertensive (n = 1238) according to history of
      hypertension or clinic blood pressure greater than 140 mmHg systolic or greater
      than 90 mmHg diastolic at baseline visits. RESULTS: Hypertensive patients were
      older, more obese, and included more women (all P < 0.05). Furthermore, the
      hypertensive group had higher wall thicknesses and left ventricular mass and
      higher prevalence of left ventricular hypertrophy (40 vs. 25%) and increased
      relative wall thickness (21 vs. 14%, both P < 0.01). On the basis of aortic valve
      area and energy loss the degree of aortic valve stenosis did not differ between
      the groups. In multivariate analysis, hypertension predicted higher left
      ventricular mass independent of other well known confounders including male sex,
      circumferential end-systolic stress, body mass index, aortic regurgitation, left
      ventricular ejection fraction and severity of aortic stenosis (multiple R = 0.30,
      P < 0.001). CONCLUSION: In patients with asymptomatic aortic stenosis,
      concomitant hypertension significantly influences left ventricular geometry and
      is associated with higher left ventricular mass, relative wall thickness and
      higher prevalence of left ventricular hypertrophy.

PMID- 19844184
TI  - Diabetes and incident heart failure in hypertensive and normotensive participants
      of the Strong Heart Study.
AB  - OBJECTIVES: Type 2 diabetes is accepted as a cause of heart failure, but direct
      cause-effect evidence independent of incident myocardial infarction (MI),
      hypertension and other coexisting risk factors is less well studied. We tested
      the hypothesis that diabetes predisposes to heart failure independently of
      hypertension and intercurrent MI. METHODS: We evaluated 12-year incident heart
      failure in 2740 participants (1781 women) without prevalent cardiovascular or
      severe kidney disease, at the time of the first exam of the Strong Heart Study
      cohort. Intercurrent MI was censored as a competing risk event. RESULTS: Diabetes
      was present in 1206 individuals (44%), and impaired fasting glucose (IFG) in 391
      (14%). Diabetic participants more frequently had hypertension and/or central
      obesity (both P < 0.0001). Incident heart failure was ascertained in 64
      participants with normal fasting glucose (NFG; 6%), 26 (7%) with IFG and 201 with
      diabetes (17%, hazard ratio = 4.04 vs. NFG, P < 0.0001). In Cox analysis
      adjusting for age, sex, obesity, central fat distribution, hypertension,
      antihypertensive medications, prevalent atrial fibrillation, glomerular
      filtration rate, urinary albumin/creatinine ratio, plasma cholesterol, Hb1Ac,
      smoking habit, alcohol use, educational level and physical activity, diabetes was
      associated with a two-fold greater risk of incident heart failure than NFG
      (hazard ratio = 2.45, P < 0.0001). Diabetes maintained 1.5-fold greater risk of
      heart failure than NFG (P < 0.03) even when intercurrent MI (n = 221) was
      censored as a competing risk event, similar to the adjusted hazard ratio for
      heart failure in hypertension. CONCLUSION: Type 2 diabetes is a potent,
      independent risk factor for heart failure. Risk of heart failure in diabetic
      patients cannot be fully explained by incident MI and coexisting cardiovascular
      risk factors. Mechanisms directly related to diabetes and impairing cardiac
      function should be studied and identified.

PMID- 19844186
TI  - Medication room madness: calming the chaos.
AB  - Nurses work in stressful environments, encountering interruptions and
      distractions at almost every turn. The aim of this medication safety project was
      to improve the physical design and organizational layout of the medication room,
      reduce nurse interruptions and distractions, and create a standard medication
      process for enhanced patient safety and efficiency. This successful change
      improved the medication administration process, decreased medication errors, and
      enhanced nursing satisfaction.

PMID- 19844187
TI  - Epidermal growth factor receptor mutation and pathologic-radiologic correlation
      between multiple lung nodules with ground-glass opacity differentiates
      multicentric origin from intrapulmonary spread.
AB  - INTRODUCTION: No standard guidelines detailing recommendations for the selection
      and treatment for multiple lung nodules with ground-glass opacity (GGO) have been
      established. For treatment decision, we analyzed epidermal growth factor receptor
      (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in
      multiple lung nodules presented as GGO to differentiate multifocal lesions from
      intrapulmonary spread. METHODS: Twenty-four patients with multiple lung nodules
      presented as GGO were identified to investigate somatic mutations of EGFR (exon
      18-21) and K-ras (codons 2, 13, and 61). This series included 18 atypical
      adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23
      adenocarcinomas (ADC) obtained from 24 patients. RESULTS: High frequency of
      discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality
      (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR
      mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4,
      AAH and BAC had different mutational changes, and in case 10, the BAC lesion
      contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had
      more mutational changes than the carcinoma. The pure GGO appearance in the
      radiologic examination corresponded preinvasive pathologic change. CONCLUSIONS:
      This study showed that synchronous BAC and/or ADC can have different EGFR or K
      ras mutational profiles suggesting these lesions arise as independent events
      rather than intrapulmonary spread or systemic metastasis. This has significant
      implication in staging and treatment. These findings might be a clue to establish
      guidelines of the multiple neoplastic lung nodules with GGO.

PMID- 19844188
TI  - Detection of depression in patients with low vision.
AB  - PURPOSE: Depression is common in people with vision impairment and further
      reduces levels of functioning independent of vision loss. However, depression
      most often remains undetected and untreated this group. Eye health professionals
      (EHPs) (ophthalmic nurses, ophthalmologists, optometrists, and orthoptists) and
      rehabilitation workers (RWs) may be able to play a role in detecting depression.
      This study aimed to identify current practice and investigate factors associated
      with depression management strategies. METHODS: A self-administered cross
      sectional survey of EHPs and RWs assessed current practice including confidence
      in working with depressed people with vision impairment; barriers to recognition,
      assessment, and management of depression; beliefs about the consequences,
      duration, and efficacy of treatment for depression in individuals with vision
      impairment. RESULTS: Ninety-four participants aged 23 to 69 years took part.
      Thirty-seven participants (39.8%) stated that they attempted to identify
      depression as part of patient management, with RWs significantly more likely to
      do so (n = 17, 60.7%) than EHPs (n = 20, 30.8%; p = 0.007). Intention to identify
      depression was not associated with sociodemographic factors, professional
      experience in eye care services, or the length and number of patient
      consultations, but a significant relationship was found for confidence, barriers,
      and beliefs about depression (p < 0.05). No consistent depression management
      strategy emerged and a range of barriers were highlighted. CONCLUSIONS: Training
      programs are needed to provide EHPs and RWs with the skills and resources to
      address depression in people with vision loss under their care and to support the
      development of procedures by which concerns about depression can be identified
      objectively, documented, and included as part of a referral to appropriate
      services.

PMID- 19844189
TI  - Photoreceptor layer map using spectral-domain optical coherence tomography.
AB  - PURPOSE: To develop a novel method for analysis of the photoreceptor layer map
      (PLM) generated using spectral-domain optical coherence tomography (OCT).
      METHODS: OCT scans were obtained from 20 eyes, 10 with macular holes (MH) and 10
      with central serous chorioretinopathy (CSC) using the Macular Cube (512 x 128)
      protocol of the Cirrus HD-OCT (Carl Zeiss). The scanned data were processed using
      embedded tools of the advanced visualization. A partial thickness OCT fundus
      image of the photoreceptor layer was generated by setting the region of interest
      to a 50-microm thick layer that was parallel and adjacent to the retinal pigment
      epithelium. The resulting image depicted the photoreceptor layer as a map of the
      reflectivity in OCT. The PLM was compared with fundus photography, auto
      fluorescence, tomography, and retinal thickness map. RESULTS: The signal from the
      photoreceptor layer of every OCT scan in each case was demonstrated as a single
      image of PLM in a fundus photograph fashion. In PLM images, detachment of the
      sensory retina is depicted as a hypo-reflective area, which represents the base
      of MH and serous detachment in CSC. Relative hypo-reflectivity, which was also
      noted at closed MH and at recently reattached retina in CSC, was associated with
      reduced signal from the junction between the inner and outer segments of
      photoreceptors in OCT images. Using PLM, changes in the area of detachment and
      reflectivity of the photoreceptor layer could be efficiently monitored.
      CONCLUSIONS: The photoreceptor layer can be analyzed as a map using spectral
      domain OCT. In the treatment of both MH and CSC, PLM may provide new pathological
      information about the photoreceptor layer to expand our understanding of these
      diseases.

PMID- 19844190
TI  - Astigmatic changes in orthokeratology.
AB  - PURPOSE: To investigate and compare changes in refractive astigmatism and corneal
      toricity in orthokeratology (ortho-k) using the Thibos vector analysis. METHODS:
      Consecutive records of 74 patients (aged 7 to 16 years) who were fitted with
      spherical ortho-k lenses at the Optometry Clinic of The Hong Kong Polytechnic
      University between April 2000 and November 2003 and who had been on the treatment
      for at least 6 months were reviewed. Manifest refractive error and topographic
      data were retrieved from the right eye for data analysis. Changes in refractive
      astigmatism and corneal toricity were evaluated using the Thibos vectors
      (refractive vectors, RJ 0 and RJ 45; corneal vectors, CJ 0 and CJ 45) among the
      astigmats (refractive astigmatism 0.75 diopters cylinder (DC) or above) and the
      non-astigmats (refractive astigmatism 0.50 DC or less). RESULTS: The mean changes
      in refractive astigmatism, RJ 0 and RJ 45 were 0.51 +/- 0.51 diopter (D), -0.31
      +/- 0.35 D, and 0.09 +/- 0.16 D, respectively, among the astigmats; and 0.01 +/-
      0.36 D, 0.00 +/- 0.17 D, and 0.03 +/- 0.13 D, respectively, among the non
      astigmats. RJ 0 was significantly reduced, and RJ 45 was significantly increased
      only in the astigmats (one sample t tests, astigmats: p < 0.01; non-astigmats: p
      > 0.10). Although there were significant correlations between the initial RJ 0
      and RJ 45 with their changes in all subjects and in the astigmats, only 21 to 55%
      of the variability could be explained by the regression equations (Pearson r: all
      subjects -0.63 < r < -0.62; astigmats -0.74 < r < -0.46, p < 0.001). No
      significant changes in corneal toricity and no correlations between the changes
      in refractive astigmatism and changes in corneal toricity were found (p > 0.13).
      CONCLUSIONS: Spherical ortho-k leads to significant changes in RJ0 and RJ45, but
      only 38% of the variance of the changes in all subjects could be explained by
      relationship between changes and the initial RJ0 or RJ45. No correlation between
      changes in refractive astigmatism and changes in corneal toricity was found, and
      ortho-k treatment did not induce astigmatism in our non-astigmatic subjects.

PMID- 19844191
TI  - Noninvasive in vivo small animal MRI and MRS: basic experimental procedures.
AB  - Small animal Magnetic Resonance (MR) research has emerged as an important element
      of modern biomedical research due to its non-invasive nature and the richness of
      biological information it provides. MR does not require any ionizing radiation
      and can noninvasively provide higher resolution and better signal-to-noise ratio
      in comparison to other tomographic or spectroscopic modalities. In this protocol,
      we will focus on small animal MR imaging and MR spectroscopy (MRI/MRS) to
      noninvasively acquire relaxation weighted (1)H images of mouse and to obtain
      (31)P spectra of mouse muscle. This work does not attempt to cover every aspect
      of small animal MRI/MRS but rather introduces basic procedures of mouse MRI/MRS
      experiments. The main goal of this work is to inform researchers of the basic
      procedures for in vivo MR experiments on small animals. The goal is to provide a
      better understanding of basic experimental procedures to allow researchers new to
      the MR field to better plan for non-MR components of their studies so that both
      MR and non-MR procedures are seamlessly integrated.

PMID- 19844192
TI  - Low-level shRNA cytotoxicity can contribute to MYC-induced hepatocellular
      carcinoma in adult mice.
AB  - Short hairpin RNAs (shRNAs) have emerged as a novel therapeutic modality, but
      there is increasing concern over nonspecific effects in vivo. Here, we used viral
      vectors to express shRNAs against endogenous p53 in livers of conditional MYC
      transgenic mice. As expected, the shRNAs silenced hepatic p53 and accelerated
      liver tumorigenesis when MYC was concurrently expressed. Surprisingly, various
      irrelevant control shRNAs similarly induced a rapid onset of tumorigenesis,
      comparable to carbon tetrachloride (CCl4), a potent carcinogen. We found that
      even marginal shRNA doses can already trigger histologically detectable
      hepatoxicity and increased hepatocyte apoptosis. Moreover, we noted that shRNA
      expression globally dysregulated hepatic microRNA (miRNA) expression, and that
      shRNA levels and activity further increased in the presence of MYC. In MYC
      expressing transgenic mice, the marginal shRNA-induced liver injury sufficed to
      further stimulate hepatocellular division that was in turn associated with
      markedly increased expression of the mitotic cyclin B1. Hence, even at low doses,
      shRNAs can cause low-level hepatoxicity that can facilitate the ability of the
      MYC oncogene to induce liver tumorigenesis. Our data warrant caution regarding
      the possible carcinogenic potential of shRNAs when used as clinical agent,
      particularly in circumstances where tissues are genetically predisposed to
      cellular transformation and proliferation.

PMID- 19844193
TI  - Prevention of dystrophic pathology in severely affected dystrophin/utrophin
      deficient mice by morpholino-oligomer-mediated exon-skipping.
AB  - Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by
      mutations in the dystrophin gene that result in the absence of functional
      protein. Antisense-mediated exon-skipping is one of the most promising approaches
      for the treatment of DMD because of its capacity to correct the reading frame and
      restore dystrophin expression, which has been demonstrated in vitro and in vivo.
      In particular, peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs)
      have recently been shown to induce widespread high levels of dystrophin
      expression in the mdx mouse model. Here, we report the efficiency of the PPMO
      mediated exon-skipping approach in the utrophin/dystrophin double-knockout mouse
      (dKO) mouse, which is a much more severe and progressive mouse model of DMD.
      Repeated intraperitoneal (i.p.) injections of a PPMO targeted to exon 23 of
      dystrophin pre-mRNA in dKO mice induce a near-normal level of dystrophin
      expression in all muscles examined, except for the cardiac muscle, resulting in a
      considerable improvement of their muscle function and dystrophic pathology. These
      findings suggest great potential for PPMOs in systemic treatment of the DMD
      phenotype.

PMID- 19844194
TI  - Supplying clotting factors from hematopoietic stem cell-derived erythroid and
      megakaryocytic lineage cells.
AB  - Systemically distributed proteins such as clotting factors have been
      traditionally expressed from muscle or liver to achieve therapeutic, long-term
      expression. As long-lived cell capable of generating an abundant progeny,
      hematopoietic stem cells (HSCs) also merit consideration for this purpose. To be
      clinically relevant, this approach would require that hematopoietic cells be
      capable of expressing high levels of functional, secreted proteins, that the risk
      of insertional oncogenesis be minimized, and that sufficient stem cell
      engraftment be achieved following minimally invasive conditioning. Recent reports
      demonstrate the feasibility of expressing either factor IX (FIX) or factor VIII
      (FVIII) in erythroblasts and platelets using lineage-restricted vectors,
      resulting in effective treatments in mouse models of hemophilia. The erythroid
      system is especially powerful in providing high protein output, yielding FIX
      levels approaching 1 micro g/ml per vector copy in the plasma of long-term
      hematopoietic chimeras, a secretion level that vastly outperforms any other
      current mammalian constitutive or long-terminal repeat (LTR)-driven vector
      system. These early but promising studies raise the prospect of further
      developing these strategies for clinical investigation.

PMID- 19844195
TI  - Gene therapy of MPL deficiency: challenging balance between leukemia and
      pancytopenia.
AB  - Signaling of the thrombopoietin (THPO) receptor MPL is critical for the
      maintenance of hematopoietic stem cells (HSCs) and megakaryocytic
      differentiation. Inherited loss-of-function mutations of MPL cause severe
      thrombocytopenia and aplastic anemia, a syndrome called congenital
      amegakaryocytic thrombocytopenia (CAMT). With the aim to assess the toxicity of
      retroviral expression of Mpl as a basis for further development of a gene therapy
      for this disorder, we expressed Mpl in a murine bone marrow transplantation (BMT)
      model. Treated mice developed a profound yet transient elevation of multilineage
      hematopoiesis, which showed morphologic features of a chronic myeloproliferative
      disorder (CMPD) with progressive pancytopenia. Ten percent of mice (3/27)
      developed erythroleukemia, associated with insertional activation of Sfpi1 and
      Fli1. The majority of transplanted mice developed a progressive pancytopenia with
      histopathological features of a myelodysplastic syndrome (MDS)-like disorder. To
      avoid these adverse reactions, improved retroviral vectors were designed that
      mediate reduced and more physiological Mpl expression. Self-inactivating gamma
      retroviral vectors were constructed that expressed Mpl from the phosphoglycerate
      kinase (PGK) or the murine Mpl promoter. Mice that received BM cells expressing
      Mpl from the Mpl promoter were free of any previously observed adverse reactions.

PMID- 19844196
TI  - A self-inactivating gamma-retroviral vector reduces manifestations of
      mucopolysaccharidosis I in mice.
AB  - Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease due to deficiency
      in alpha-L-iduronidase (IDUA) that results in accumulation of glycosaminoglycans
      (GAGs) throughout the body, causing numerous clinical defects. Intravenous
      administration of a gamma-retroviral vector (gamma-RV) with an intact long
      terminal repeat (LTR) reduced the clinical manifestations of MPS I, but could
      cause insertional mutagenesis. Although self-inactivating (SIN) gamma-RVs in
      which the enhancer and promoter elements in the viral LTR are absent after
      transduction reduces this risk, such vectors could be less effective. This report
      demonstrates that intravenous (i.v.) injection of a SIN gamma-RV expressing
      canine IDUA from the liver-specific human alpha(1)-antitrypsin promoter into
      adult or newborn MPS I mice completely prevents biochemical abnormalities in
      several organs, and improved bone disease, vision, hearing, and aorta to a
      similar extent as was seen with administration of the LTR-intact vector to
      adults. Improvements were less profound than when using an LTR-intact gamma-RV in
      newborns, which likely reflects a lower level of transduction and expression for
      the SIN vector-transduced mice, and might be overcome by using a higher dose of
      SIN vector. A SIN gamma-RV vector ameliorates clinical manifestations of MPS I in
      mice and should be safer than an LTR-intact gamma-RV.

PMID- 19844197
TI  - Adipose tissue-derived mesenchymal stem cells expressing prodrug-converting
      enzyme inhibit human prostate tumor growth.
AB  - The ability of human adipose tissue-derived mesenchymal stem cells (AT-MSCs),
      engineered to express the suicide gene cytosine deaminase::uracil
      phosphoribosyltransferase (CD::UPRT), to convert the relatively nontoxic 5
      fluorocytosine (5-FC) into the highly toxic antitumor 5-fluorouracil (5-FU)
      together with their ability to track and engraft into tumors and micrometastases
      makes these cells an attractive tool to activate prodrugs directly within the
      tumor mass. In this study, we tested the feasibility and efficacy of these
      therapeutic cells to function as cellular vehicles of prodrug-activating enzymes
      in prostate cancer (PC) therapy. In in vitro migration experiments we have shown
      that therapeutic AT-MSCs migrated to all the prostate cell lines tested. In a
      pilot preclinical study, we observed that coinjections of human bone metastatic
      PC cells along with the transduced AT-MSCs into nude mice treated with 5-FC
      induced a complete tumor regression in a dose dependent manner or did not even
      allow the establishment of the tumor. More importantly, we also demonstrated that
      the therapeutic cells were effective in significantly inhibiting PC tumor growth
      after intravenous administration that is a key requisite for any clinical
      application of gene-directed enzyme prodrug therapies.

PMID- 19844198
TI  - Enhanced antitumor efficacy of vasculostatin (Vstat120) expressing oncolytic HSV
      1.
AB  - Oncolytic viral (OV) therapy is a promising therapeutic modality for brain
      tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular
      fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific
      receptor. To date, the therapeutic efficacy of Vstat120 delivery into established
      tumors has not been investigated. Here we tested the therapeutic efficacy of
      combining Vstat120 gene delivery in conjunction with OV therapy. We constructed
      RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses
      Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter.
      Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was
      retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO
      produced Vstat120 efficiently inhibited endothelial cell migration and tube
      formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited
      angiogenesis (P = 0.007) in vivo. There was a significant suppression of
      intracranial and subcutaneous glioma growth in mice treated with RAMBO compared
      to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically
      significant reduction in tumor vascular volume fraction (VVF) and microvessel
      density (MVD) was observed in tumors treated with RAMBO. This is the first study
      to report the antitumor effects of Vstat120 delivery into established tumors and
      supports the further development of RAMBO as a possible cancer therapy.

PMID- 19844199
TI  - Half doses of PEG-ES and senna vs. high-dose senna for bowel cleansing before
      colonoscopy: a randomized, investigator-blinded trial.
AB  - OBJECTIVES: Patients' compliance with and tolerance of large-volume polyethylene
      glycol electrolyte solution (PEG-ES) have prompted continuous investigation with
      alternative forms of cleansing. High-dose senna is superior to PEG-ES for the
      quality of bowel cleansing, patient compliance, and tolerance, but its acceptance
      may be influenced by the incidence of abdominal pain. We hypothesized that a
      combination of half doses of PEG-ES and senna could minimize the incidence of
      abdominal pain without affecting the quality of bowel preparation. METHODS: This
      randomized, investigator-blinded trial has been conducted on consecutive
      outpatients scheduled for elective colonoscopy at a single community-based
      hospital. Patients were randomly assigned to receive either 12 tablets of 12 mg
      senna and 2 l of PEG-ES (half-dose group, HDG) or 24 tablets of senna divided in
      two doses (senna group, SG) the day before colonoscopy. The main outcome measures
      were the quality of colon cleansing (Aronchick scoring scale) and the incidence
      of preparation-related abdominal pain. Secondary outcome measures were patients'
      compliance with the cleansing regimen, overall tolerability, prevalence of
      predefined side effects, and quality of right colon cleansing. RESULTS: A total
      of 296 patients were enrolled (HDG=151 and SG=145). Overall cleansing was
      excellent to good in 90.1 and 88.3% patients in HDG and SG, respectively
      (P=0.62). Preparation-related moderate-to-severe abdominal pain was reported by
      6% patients in HDG and 15.2% in SG (P=0.009). No significant differences were
      observed for secondary outcomes. CONCLUSIONS: The regimen combining half doses of
      PEG-ES and senna provides high-quality bowel preparation and acceptable patient
      tolerance, with less abdominal pain compared with high-dose senna.

PMID- 19844200
TI  - Intestinal permeability in cirrhotic patients with and without spontaneous
      bacterial peritonitis: is the ring closed?
AB  - OBJECTIVES: Impaired intestinal permeability (IP) may have a role in the
      pathogenesis of ascites and in spontaneous bacterial peritonitis (SBP) in
      patients with liver cirrhosis (LC). The aim of this study was to assess IP in LC
      patients with respect to healthy controls. METHODS: IP was evaluated by the
      (51)Cr-ethylenediaminetetraacetic acid ((51)Cr-EDTA) permeability test in 52 LC
      patients and in 48 sex- and age-matched controls. The presence of (51)Cr-EDTA was
      also evaluated in ascitic fluid after therapeutic paracentesis in all LC patients
      with ascites. RESULTS: An altered IP was found in 45% of LC patients compared
      with 4% of controls (P<0.00001). IP impairment was significantly associated with
      Child-Pugh status (75% of Child C patients vs. 39% of Child B and 22% of Child A
      patients), with the presence of ascites (60% in ascitic patients vs. 31% in
      nonascitic patients), and with a history of SBP (100% of patients with SBP vs.
      50% of those without SBP). (51)Cr-EDTA was present in all ascitic samples
      obtained from patients with SBP compared with 22% of patients without SBP.
      CONCLUSIONS: IP derangement was a common finding in LC, especially in patients
      with more advanced disease (presence of ascites and history of SBP). The presence
      of (51)Cr-EDTA in ascites in patients with SBP suggests an altered permeability
      of splancnic vessels and/or peritoneal membranes. Further studies are required to
      assess (51)Cr-EDTA urine and ascite cutoffs to set up SBP preventive strategies.

PMID- 19844201
TI  - Connections between genetics and clinical data: Role of MCP-1, CFTR, and SPINK-1
      in the setting of acute, acute recurrent, and chronic pancreatitis.
AB  - OBJECTIVES: Acute, acute recurrent, and chronic pancreatitis are inflammatory
      diseases with multifactorial pathogenic mechanisms. Genetic mutations and
      polymorphisms have been correlated with pancreatitis. The aim of this study was
      to investigate the association of cystic fibrosis transmembrane conductance
      regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1) gene
      mutations and monocyte chemoattractant protein 1 (MCP-1) -2518A/G polymorphism
      with acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic
      pancreatitis (CP), and to associate genetic backgrounds with clinical phenotype
      in these three conditions. METHODS: One hundred eighteen AP, 64 ARP, 142 CP
      patients, and 88 normal controls were enrolled consecutively. We analyzed MCP-1
      serum levels using enzyme-linked immunosorbent assay. Polymorphism -2518 of MCP-1
      and SPINK-1 N34S gene mutations were determined by PCR-restriction-fragment
      length polymorphism. Sequence analysis was performed when necessary. Thirty-three
      CFTR mutations were analyzed in CP and ARP patients using multiplex DNA testing.
      RESULTS: Serum MCP-1 levels were significantly higher in all patients affected by
      pancreatic inflammatory diseases. Moreover, we found a significant over
      representation of the MCP-1G allele in ARP patients. We found a statistically
      significant association of CFTR gene mutations with ARP, but not with CP. We did
      not find a statistically significant association of ARP or CP with the N34S SPINK
      1 gene mutation. Interestingly, 39 of 64 ARP patients (61%) carried at least one
      genetic mutation and/or polymorphism. Five of 64 ARP patients had pancreas
      divisum and four of these five also carried the G allele. CONCLUSIONS: Analysis
      of a comprehensive range of potential susceptibility variants is needed to
      support modeling of the effects of genes and environment in pancreatitis. As
      such, beyond gene mutations, the context within which those mutations exist must
      be considered. In pancreatitis the context includes the inflammatory response,
      clinical features, and exogenous factors.

PMID- 19844202
TI  - Onset and risk factors for fecal incontinence in a US community.
AB  - OBJECTIVES: The natural history of fecal incontinence (FI) in community subjects
      is uncertain and the onset rate is unknown. The aim of the study is to estimate
      the prevalence, new-onset rate, and risk factors for FI in community subjects.
      METHODS: A random sample of 2,400 community subjects aged > or =50 years was
      surveyed in 1993, using a validated questionnaire. Responders were recontacted in
      2003. FI was defined as self-reported problems with leakage of stool. Onset rate
      was calculated as the proportion of subjects without FI who became new cases.
      Logistic regression models were constructed to identify predictive factors for
      developing FI and changes in bowel habit associated with the onset of FI.
      RESULTS: Overall, 1,540 (64%) subjects responded to the initial survey, and 674
      (44%) of them responded to the second survey a median of 9 (8.8-9.5) years later.
      The prevalence of FI in the first survey was 15.3% (13.4-17.3%). In the second
      survey, 37 reported incident FI; thus, the onset rate of FI was 7.0% (5.0-9.6)
      per 10 years. Predictive factors at baseline for the onset of FI were self
      reported diarrhea (odds ratio (OR)=3.8 (1.5, 9.4)), incomplete evacuation (OR=3.4
      (1.2, 9.8)), and pelvic radiation (OR=5.1 (1.01, 25.9)). Development of urgency
      was the primary predictor among the set of predictors reflecting changes in bowel
      symptoms that were associated with the onset of FI (OR=24.9 (10.6, 58.4)).
      CONCLUSIONS: The onset rate of FI is approximately 7% per 10 years in community
      subjects aged > or =50 years. Prevention may be possible if bowel habit is
      appropriately managed in high-risk individuals.

PMID- 19844203
TI  - Classification of the severity of acute pancreatitis: how many categories make
      sense?
AB  - There is an ongoing effort to revise the 1992 Atlanta classification of acute
      pancreatitis in the light of emerging evidence. The categorization of the
      severity of acute pancreatitis is one of the key elements of the classification.
      This paper aims to define the optimal number of categories and provide their
      definitions on sound clinical grounds.

PMID- 19844204
TI  - Clostridium difficile is associated with poor outcomes in patients with
      cirrhosis: A national and tertiary center perspective.
AB  - OBJECTIVES: Clostridium difficile-associated disease (CDAD) is associated with
      antibiotic use, acid suppression, and hospitalization, all of which occur
      frequently in cirrhosis. The aim was to define the effect of CDAD on outcomes and
      identify risk factors for its development in cirrhosis. METHODS: Case-control
      studies using the de-identified national (Nationwide Inpatient Sample, NIS) and
      an identified liver transplant center database of hospitalized cirrhotics with
      and without CDAD were performed. The NIS 2005 was queried for mortality, charges,
      and length of stay (LOS) in cirrhotics with/without CDAD. Outcomes of cirrhosis
      and infections were also analyzed. In the transplant center database, risk
      factors for CDAD were defined in hospitalized cirrhotics with/without CDAD who
      were age matched in a 1:2 ratio. RESULTS: The NIS 2005 included 1,165 cirrhotics
      with and 82,065 without CDAD. Cirrhotics with CDAD had a significantly higher
      mortality (13.8% vs. 8.2%, P<0.001), LOS (14.4 days vs. 6.7 days, P<0.001), and
      charges ($79,351 vs. $35,686, P<0.001) compared with those without CDAD. On
      multivariate analysis, CDAD was associated with higher mortality (odds ratio (OR)
      1.55, 95% confidence interval (CI) 1.29-1.85), charges, and LOS despite
      controlling for cirrhosis complications and infections. In the transplant center
      database, 54 cirrhotics with and 108 cirrhotics without CDAD were included.
      Outpatient spontaneous bacterial peritonitis prophylaxis (35% vs. 13%, P=0.01),
      inpatient antibiotic (63% vs. 35%, P=0.0001), and proton pump inhibitor (PPI) use
      (74% vs. 31%, P=0.0001) were significantly higher in those with CDAD.
      CONCLUSIONS: Cirrhotics with CDAD have a higher mortality, LOS, and charges on
      the NIS 2005 compared with those without CDAD. Antibiotic and PPI use are risk
      factors for CDAD development in hospitalized cirrhotics.

PMID- 19844205
TI  - Sequential therapy or triple therapy for Helicobacter pylori infection:
      systematic review and meta-analysis of randomized controlled trials in adults and
      children.
AB  - OBJECTIVES: Eradication rates with triple therapy (TT) for Helicobacter pylori
      infection have declined to unacceptable levels. Sequential therapy (ST) is a
      novel treatment that has shown promise in several controlled trials. Our aim was
      to assess the efficacy of ST in adults and children compared with that of TT by
      performing a systematic review and meta-analysis. METHODS: We performed an
      electronic search of the following: Cochrane Trial Register (until Issue 4,
      2008), MEDLINE (1966 to 21 October 2008), EMBASE (1980 to 21 October 2008), and
      abstracts from the major US, European, and Asian gastroenterology conferences.
      Randomized controlled trials (RCTs) and controlled clinical trials with a
      parallel group design comparing the ST with a TT lasting at least 7 days were
      used. RESULTS: Ten RCTs enrolled 3,006 adult patients and the odds ratio (OR) for
      eradication of H. pylori with ST compared with TT was 2.99 (95% confidence
      interval (CI): 2.47-3.62), giving a number needed to treat (NNT) of 6 (95% CI: 5
      7) favoring ST. There was no publication bias. The OR for eradication with ST
      compared with 10-day TT was 2.92 (95% CI: 1.95-4.38), yielding an NNT of 8 (95%
      CI: 6-12), favoring ST. In patients with clarithromycin resistance, the OR for
      eradication with ST was 10.21 (95% CI: 3.01-34.58) compared with TT, but the
      numbers studied are small. Three RCTs enrolled 260 children and adolescents, and
      the OR for eradication was 1.98 (95% CI: 0.96-4.07). There was no difference in
      the rate of side effects between the ST and the TT (OR, 1.01; 95% CI: 0.78-1.30).
      CONCLUSIONS: ST appears to be better than TT in the eradication of H. pylori.
      This is a promising therapy, but further trials are needed in other European
      countries and North America before it can be recommended as a first-line
      treatment.

PMID- 19844206
TI  - Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2:
      association with major depression and antidepressant response in Mexican
      Americans.
AB  - We studied seven genes that reflect events relevant to antidepressant action at
      four sequential levels: (1) entry into the brain, (2) binding to monoaminergic
      transporters, and (3) distal effects at the transcription level, resulting in (4)
      changes in neurotrophin and neuropeptide receptors. Those genes are ATP-binding
      cassette subfamily B member 1 (ABCB1), the noradrenaline, dopamine, and serotonin
      transporters (SLC6A2, SLC6A3 and SLC6A4), cyclic AMP-responsive element binding
      protein 1 (CREB1), corticotropin-releasing hormone receptor 1 (CRHR1) and
      neurotrophic tyrosine kinase type 2 receptor (NTRK2). Sequence variability for
      those genes was obtained in exonic and flanking regions. A total of 56 280 000 bp
      across were sequenced in 536 unrelated Mexican Americans from Los Angeles (264
      controls and 272 major depressive disorder (MDD)). We detected in those
      individuals 419 single nucleotide polymorphisms (SNPs); the nucleotide diversity
      was 0.00054 + or - 0.0001. Of those, a total of 204 novel SNPs were identified,
      corresponding to 49% of all previously reported SNPs in those genes: 72 were in
      untranslated regions, 19 were in coding sequences of which 7 were non-synonymous,
      86 were intronic and 27 were in upstream/downstream regions. Several SNPs or
      haplotypes in ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1 and NTRK2 were associated with
      MDD, and in ABCB1, SLC6A2 and NTRK2 with antidepressant response. After
      controlling for age, gender and baseline 21-item Hamilton Depression Rating Scale
      (HAM-D21) score, as well as correcting for multiple testing, the relative
      reduction of HAM-D21 score remained significantly associated with two NTRK2
      coding SNPs (rs2289657 and rs56142442) and the haplotype CAG at rs2289658 (splice
      site), rs2289657 and rs2289656. Further studies in larger independent samples
      will be needed to confirm these associations. Our data indicate that extensive
      assessment of sequence variability may contribute to increase understanding of
      disease susceptibility and drug response. Moreover, these results highlight the
      importance of direct re-sequencing of key candidate genes in ethnic minority
      groups in order to discover novel genetic variants that cannot be simply inferred
      from existing databases.

PMID- 19844208
TI  - The accelerator hypothesis: insulin resistance as the central cause of type 1 and
      type 2 diabetes.

PMID- 19844209
TI  - Common variants near MC4R in relation to body fat, body fat distribution,
      metabolic traits and energy expenditure.
AB  - OBJECTIVE: Common variants near melanocortin receptor 4 (MC4R) have been related
      to fatness and type 2 diabetes. We examined the associations of rs17782313 and
      rs17700633 in relation to body fat, body fat distribution, metabolic traits,
      weight development and energy expenditure. METHODS: Obese young men (n = 753, BMI
      > or = 31.0 kg m(-2)) and a randomly selected group (n = 874) identified from a
      population of 174 800 men were re-examined in three surveys at mean ages 35, 46
      and 49 years (S-35, S-46 and S-49). Measurements were available at upto eight
      times from birth to adulthood. Logistic regression analysis was used to assess
      odds ratio (OR) for the presence of the carrier allele for a given difference in
      phenotypic values. RESULTS: Rs17782313 minor C-allele was associated with
      overall, abdominal and peripheral fatness (range of OR = 1.06-1.14 per z-score
      units) at all three surveys, although only consistently significant at S-35 and S
      46. Rs17700633 minor A-allele was also associated with the fatness measures, but
      significantly so only at S-49 for overall and abdominal fatness (range of OR =
      1.03-1.15 per z-score units), and peripheral fatness (OR = 1.15-1.20 per z-score
      units). There were only few significant associations with metabolic traits. The
      rs17782313 C-allele and the rs17700633 A-allele were both associated with lower
      high-density lipoprotein cholesterol (range of OR = 0.64-0.84 per mol l(-1)),
      significantly at S-46. The rs17700633 A-allele was significantly associated with
      insulin (OR = 1.25 per 50 pmol l(-1)), leptin (OR = 1.42 per 10 ng microl(-1))
      and insulin sensitivity (OR = 0.81 per model unit). The rs17782313 C-allele and
      the rs17700633 A-allele were both associated with BMI in childhood and
      adolescence (range of OR = 1.04-1.17 per z-score units), significant for the
      rs17782313 C-allele at the age of 13-19 years and for rs17700633 A-allele at age
      7, 10, 13 and 19 years. No significant associations were found for energy
      expenditure. CONCLUSION: Near MC4R variants appear to contribute to body fat,
      body fat distribution, some metabolic traits, weight development during
      childhood, but not to energy expenditure.

PMID- 19844207
TI  - Replication of association between schizophrenia and ZNF804A in the Irish Case
      Control Study of Schizophrenia sample.
AB  - A recent genome-wide association study reported association between schizophrenia
      and the ZNF804A gene on chromosome 2q32.1. We attempted to replicate these
      findings in our Irish Case-Control Study of Schizophrenia (ICCSS) sample (N=1021
      cases, 626 controls). Following consultation with the original investigators, we
      genotyped three of the most promising single-nucleotide polymorphisms (SNPs) from
      the Cardiff study. We replicate association with rs1344706 (trend test one-tailed
      P=0.0113 with the previously associated A allele) in ZNF804A. We detect no
      evidence of association with rs6490121 in NOS1 (one-tailed P=0.21), and only a
      trend with rs9922369 in RGRIP1L (one-tailed P=0.0515). On the basis of these
      results, we completed genotyping of 11 additional linkage disequilibrium-tagging
      SNPs in ZNF804A. Of 12 SNPs genotyped, 11 pass quality control criteria and 4 are
      nominally associated, with our most significant evidence of association at
      rs7597593 (P=0.0013) followed by rs1344706. We observe no evidence of
      differential association in ZNF804A on the basis of family history or sex of
      case. The associated SNP rs1344706 lies in approximately 30 bp of conserved
      mammalian sequence, and the associated A allele is predicted to maintain binding
      sites for the brain-expressed transcription factors MYT1l and POU3F1/OCT-6. In
      controls, expression is significantly increased from the A allele of rs1344706
      compared with the C allele. Expression is increased in schizophrenic cases
      compared with controls, but this difference does not achieve statistical
      significance. This study replicates the original reported association of ZNF804A
      with schizophrenia and suggests that there is a consistent link between the A
      allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia.

PMID- 19844210
TI  - Metabolic responses to long-term pharmacological inhibition of CB1-receptor
      activity in mice in relation to dietary fat composition.
AB  - BACKGROUND AND OBJECTIVES: The antiobesity effects of suppressed endocannabinoid
      signaling may rely, at least in part, on changes in lipid fluxes. As fatty acids
      exert specific effects depending on their level of saturation, we hypothesized
      that the dietary fatty acid composition would influence the outcome of treatment
      with a CB(1)-receptor antagonist (rimonabant). METHODS: Mice were treated with
      rimonabant (10 mg kg(-1) body weight per day) or vehicle while equicalorically
      fed either a low-fat diet (LF), a high-fat (HF) diet or an HF diet in which 10%
      of the saturated fatty acids (SFAs) were replaced by poly-unsaturated fatty acids
      (PUFA) from fish oil (FO). Food intake and body weight were registered daily.
      Indirect calorimetry was performed and feces were collected. After 3 weeks, mice
      were killed for blood and tissue collection. RESULTS: Relative to the LF diet,
      the HF diet caused anticipated metabolic derangements, which were partly reversed
      by the HF/FO diet. The HF/FO diet, however, was most obesity-promoting despite
      inhibiting lipogenesis as indicated by low gene expression levels of lipogenic
      enzymes. On all three diets, rimonabant treatment improved metabolic derangements
      and led to significantly lower body weight gain than their respective controls.
      This latter effect appeared largest in the HF/FO group, but occurred without
      major changes in nutrient absorption and energy expenditure. CONCLUSION: The
      effects of chronic rimonabant treatment on body weight gain occurred irrespective
      of diet-induced changes in lipogenic activity, food intake and daily energy
      expenditure, and were, in fact, most pronounced in HF/FO mice. The effects of
      dietary PUFA replacement in an HF diet on expansion of adipose tissue might allow
      the favorable effects of dietary PUFA on dyslipidemia and hepatic steatosis. In
      light of other disadvantageous effects of weight gain, this might be a risky
      trade-off.

PMID- 19844211
TI  - Acute stress and food-related reward activation in the brain during food choice
      during eating in the absence of hunger.
AB  - BACKGROUND: Stress results in eating in the absence of hunger, possibly related
      to food reward perception. HYPOTHESIS: Stress decreases food reward perception.
      AIM: Determine the effect of acute stress on food choice and food choice reward
      related brain activity. SUBJECTS: Nine females (BMI = 21.5 + or - 2.2 kg/m(2),
      age = 24.3 + or - 3.5 years). PROCEDURE: Fasted subjects came twice to randomly
      complete either a rest or stress condition. Per session, two functional MRI scans
      were made, wherein the subjects chose the subsequent meal (food images). The
      rewarding value of the food was measured as liking and wanting. Food
      characteristics (for example, crispiness, fullness of taste and so on), energy
      intake, amount of each macronutrient chosen, plasma cortisol and Visual Analog
      Scale (VAS) hunger and satiety were measured. RESULTS: Fasted state was confirmed
      by high hunger (80 + or - 5 mm VAS). Breakfast energy intake (3 + or - 1 MJ) and
      liking were similar in all conditions. Wanting was lower postprandially (Delta = 
      0.3 items/category, P<0.01). Breakfast decreased hunger (-42 mm VAS, P<0.01).
      Postprandially, energy intake (-1.1 MJ), protein intake (-14.7 g) and
      carbohydrate intake (-32.7 g all P<0.05) were lower. Fat intake was not different
      (-7.3, P = 0.4). Putamen activity was not lower postprandially. Cortisol levels
      were increased in the stress condition (Area under the curve of cortisol:
      DeltaAUC = +2.2 x 10(4) nmol min(-1) l(-1), P<0.05). Satiety was lower after
      breakfast (-8 mm VAS, P<0.01). Postprandial energy intake, protein intake and
      carbohydrate intake were relatively higher compared with the rest condition,
      resulting from more choice for crispiness and fullness of taste (P<0.05). Brain
      activation was reduced in reward areas: amygdala, hippocampus and cingulate
      cortex (AUC = -13.33, -1.34, -2.56% blood oxygen level dependent (BOLD) s for
      choosing breakfast and AUC = -9.31, -1.25, -2.34%BOLD s<0.05 for choosing the
      second meal). Putamen activation was decreased postprandially (AUC = -1.2%BOLD s,
      P<0.05). CONCLUSION: Reward signaling and reward sensitivity were significantly
      lower under stress, coinciding with increased energy intake from food choice for
      more crispiness and fullness of taste. The changes in putamen activation may
      reflect specifically decreased reward prediction sensitivity.

PMID- 19844213
TI  - Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and
      indices of hepatic injury in individuals of European descent.
AB  - CONTEXT: The PNPLA3 I148M variant (rs738409) is robustly associated with hepatic
      steatosis. Intriguingly, initial findings in cohorts with a mean body mass index
      (BMI) of 30 kg m(-2) also suggested that it is associated with elevated liver
      enzymes but not with insulin resistance and dyslipidaemia. OBJECTIVE: To
      determine whether the PNPLA3 variant alters the susceptibility of morbidly obese
      subjects to develop liver injury and metabolic sequelae. PARTICIPANTS AND
      METHODS: The study was carried out in 678 obese Italians (mean BMI = 41 kg m(-2))
      who were genotyped for the I148M variant. All participants provided fasting blood
      samples and then underwent oral glucose tolerance tests. MAIN OUTCOME MEASURES:
      Indices of liver injury (alanine transaminase (ALT), aspartate transaminase
      (AST)), glucose tolerance and insulin resistance were measured. RESULTS: Markers
      of hepatic injury such as ALT and AST were significantly higher in carriers of
      the 148M allele (P = 2.2 x 10(-5) and 0.001, respectively). In all, 50% of 148M
      risk allele homozygotes had pathological levels of ALT (>40 U l(-1)) compared
      with 25% of 148I allele homozygotes (P = 0.005). Glucose tolerance and insulin
      sensitivity were similar in all three genotypes. CONCLUSION: Obese Southern
      Europeans carrying the 148M allele have increased indices of liver damage
      uncoupled from proxy measures of insulin resistance.

PMID- 19844212
TI  - The role of GNAS and other imprinted genes in the development of obesity.
AB  - Genomic imprinting is an epigenetic phenomenon affecting a small number of genes,
      which leads to differential expression from the two parental alleles. Imprinted
      genes are known to regulate fetal growth and a 'kinship' or 'parental conflict'
      model predicts that paternally and maternally expressed imprinted genes promote
      and inhibit fetal growth, respectively. In this review we examine the role of
      imprinted genes in postnatal growth and metabolism, with an emphasis on the
      GNAS/Gnas locus. GNAS is a complex imprinted locus with multiple oppositely
      imprinted gene products, including the G-protein alpha-subunit G(s)alpha that is
      expressed primarily from the maternal allele in some tissues and the G(s)alpha
      isoform XLalphas that is expressed only from the paternal allele. Maternal, but
      not paternal, G(s)alpha mutations lead to obesity in Albright hereditary
      osteodystrophy. Mouse studies show that this phenomenon is due to G(s)alpha
      imprinting in the central nervous system leading to a specific defect in the
      ability of central melanocortins to stimulate sympathetic nervous system activity
      and energy expenditure. In contrast mutation of paternally expressed XLalphas
      leads to opposite metabolic effects in mice. Although these findings conform to
      the 'kinship' model, the effects of other imprinted genes on body weight
      regulation do not conform to this model.

PMID- 19844216
TI  - Nephropharmacology: drugs and the kidney.

PMID- 19844220
TI  - Use of the MDRD study equation to estimate kidney function for drug dosing.

PMID- 19844221
TI  - Continuing the use of the Cockcroft-Gault equation for drug dosing in patients
      with impaired renal function.

PMID- 19844222
TI  - How a US regulator can encourage new science.
AB  - The Center for Drug Evaluation and Research at the US Food and Drug
      Administration (FDA) is developing a process to qualify biomarkers for use under
      particular conditions. As part of this effort, Goodsaid et al. have carried out
      work, described in this issue, on the formal qualification of novel biomarkers of
      acute renal toxicity in animals. The authors' experiences highlight the
      importance of collaboration and the role of regulators.

PMID- 19844223
TI  - How will GINA influence participation in pharmacogenomics research and clinical
      testing?
AB  - After a 13-year battle in Congress--longer than it took to map the human genome-
      the Genetic Information Nondiscrimination Act (GINA) was passed into law on 21
      May 2008. Before its passing, Francis Collins, then director of the National
      Human Genome Research Institute, testified before the 110th Congress that the
      success of personalized medicine hinged on the passing of the legislation. How
      will GINA, which takes effect in 2009, influence participation in pharmacogenomic
      research and clinical testing?

PMID- 19844224
TI  - When to conduct a renal impairment study during drug development: US Food and
      Drug Administration perspective.
AB  - To optimize drug therapy for individuals, it is critical to understand how
      various intrinsic (e.g., age, gender, race, genetics, organ impairment) and
      extrinsic factors (e.g., diet, smoking, concomitantly administered drugs) affect
      drug exposure and response.(1) Up to now, it has been far easier to discover
      effects on exposure caused by these factors, and the US Food and Drug
      Administration (FDA) has published several guidance documents with
      recommendations on how to evaluate these factors during drug development.

PMID- 19844225
TI  - Challenges in developing evidence-based drug dosing guidelines for adults and
      children receiving renal replacement therapy.
AB  - The challenges of appropriate drug dosing in patients with renal failure
      requiring renal replacement therapy (RRT) have been exacerbated by recent trends
      in both RRT technology and practices. Nearly all these changes have resulted in
      augmented drug clearance, making most existing RRT drug dosing recommendations
      obsolete. Many barriers exist to conducting research to update our knowledge of
      appropriate drug dosing in the context of contemporary RRT. Recommendations on
      how this research could be conducted, including the use of in vitro techniques,
      are offered here.

PMID- 19844226
TI  - Computational methods for discovering structural variation with next-generation
      sequencing.
AB  - In the last several years, a number of studies have described large-scale
      structural variation in several genomes. Traditionally, such methods have used
      whole-genome array comparative genome hybridization or single-nucleotide
      polymorphism arrays to detect large regions subject to copy-number variation.
      Later techniques have been based on paired-end mapping of Sanger sequencing data,
      providing better resolution and accuracy. With the advent of next-generation
      sequencing, a new generation of methods is being developed to tackle the
      challenges of short reads, while taking advantage of the high coverage the new
      sequencing technologies provide. In this survey, we describe these methods,
      including their strengths and their limitations, and future research directions.

PMID- 19844227
TI  - Next-generation gap.
AB  - There is a growing gap between the generation of massively parallel sequencing
      output and the ability to process and analyze the resulting data. New users are
      left to navigate a bewildering maze of base calling, alignment, assembly and
      analysis tools with often incomplete documentation and no idea how to compare and
      validate their outputs. Bridging this gap is essential, or the coveted $1,000
      genome will come with a $20,000 analysis price tag.

PMID- 19844228
TI  - Computation for ChIP-seq and RNA-seq studies.
AB  - Genome-wide measurements of protein-DNA interactions and transcriptomes are
      increasingly done by deep DNA sequencing methods (ChIP-seq and RNA-seq). The
      power and richness of these counting-based measurements comes at the cost of
      routinely handling tens to hundreds of millions of reads. Whereas early adopters
      necessarily developed their own custom computer code to analyze the first ChIP
      seq and RNA-seq datasets, a new generation of more sophisticated algorithms and
      software tools are emerging to assist in the analysis phase of these projects.
      Here we describe the multilayered analyses of ChIP-seq and RNA-seq datasets,
      discuss the software packages currently available to perform tasks at each layer
      and describe some upcoming challenges and features for future analysis tools. We
      also discuss how software choices and uses are affected by specific aspects of
      the underlying biology and data structure, including genome size, positional
      clustering of transcription factor binding sites, transcript discovery and
      expression quantification.

PMID- 19844229
TI  - Sense from sequence reads: methods for alignment and assembly.
AB  - The most important first step in understanding next-generation sequencing data is
      the initial alignment or assembly that determines whether an experiment has
      succeeded and provides a first glimpse into the results. In parallel with the
      growth of new sequencing technologies, several algorithms that align or assemble
      the large data output of today's sequencing machines have been developed. We
      discuss the current algorithmic approaches and future directions of these
      fundamental tools and provide specific examples for some commonly used tools.

PMID- 19844230
TI  - Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors.
AB  - BACKGROUND: Myelosuppression has been observed with several multikinase
      angiogenesis inhibitors in clinical studies, although the frequency and severity
      varies among the different agents. Inhibitors targeting vascular endothelial
      growth factor receptor (VEGFR) often inhibit other kinases, which may contribute
      to their adverse-event profiles. METHODS: Kinase selectivity of pazopanib,
      sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular
      potency was measured using autophosphorylation assays. Effect on human bone
      marrow progenitor growth in the presence of multiple growth factors was evaluated
      and correlated with the kinase selectivity. RESULTS: Sunitinib inhibited more
      kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All
      three compounds potently inhibited VEGFR-2, platelet-derived growth factor
      receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both
      kinase and cellular assays. The inhibitory properties of pazopanib, sorafenib,
      and sunitinib were dependent on the growth factor used to initiate bone marrow
      colony formation. Addition of stem cell factor and/or Flt-3 ligand with
      granulocyte-macrophage colony stimulating factor resulted in significant shifts
      in potency for sorafenib and sunitinib but less so for pazopanib. CONCLUSION:
      Activity against c-kit and Flt-3 by multikinase angiogenesis inhibitors provide a
      potential explanation for the differences in myelosuppression observed with these
      agents in patients.

PMID- 19844231
TI  - Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer.
AB  - BACKGROUND: Delta-like ligand 4 (Dll4) is a Notch ligand that is upregulated by
      hypoxia and vascular endothelial growth factor-A (VEGF-A) and is reported to have
      a role in tumor angiogenesis. Evidence from xenograft studies suggests that
      inhibiting Dll4-Notch signalling may overcome resistance to anti-VEGF therapy.
      The aim of this study was to characterise the expression of Dll4 in colon cancer
      and to assess whether it is associated with markers of hypoxia and prognosis.
      METHOD: In all, 177 colon cancers were represented in tissue microarrays.
      Immunohistochemistry was performed using validated antibodies against Dll4, VEGF,
      hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, prolyl hydroxylase (PHD)1,
      PHD2, PHD3 and carbonic anhydrase 9 (CA9). RESULTS: The expression of Dll4 was
      observed preferentially in the endothelium of 71% (125 out of 175) of colon
      cancers, but not in the endothelium adjacent to normal mucosa (none out of 107,
      P<0.0001). The expression of VEGF was significantly associated with HIF-2alpha
      (P<0.0001) and Dll4 (P=0.010). Only HIF-2alpha had a significant multivariate
      prognostic effect (hazard ratio 1.61, 95% confidence interval 1.01-2.57). Delta
      like ligand 4 was also expressed by neoplastic cells, particularly neoplastic
      goblet cells. CONCLUSION: Endothelial expression of Dll4 is not a prognostic
      factor, but is significantly associated with VEGF. Assessing endothelial Dll4
      expression may be critical in predicting response to anti-VEGF therapies.

PMID- 19844232
TI  - Hypoxia, Snail and incomplete epithelial-mesenchymal transition in breast cancer.
AB  - BACKGROUND: Hypoxia is an element of the tumour microenvironment that impacts
      upon numerous cellular factors linked to clinical aggressiveness in cancer. One
      such factor, Snail, a master regulator of the epithelial-mesenchymal transition
      (EMT), has been implicated in key tumour biological processes such as invasion
      and metastasis. In this study we set out to investigate regulation of EMT in
      hypoxia, and the importance of Snail in cell migration and clinical outcome in
      breast cancer. METHODS: Four breast cancer cell lines were exposed to 0.1% oxygen
      and expression of EMT markers was monitored. The migratory ability was analysed
      following Snail overexpression and silencing. Snail expression was assessed in
      500 tumour samples from premenopausal breast cancer patients, randomised to
      either 2 years of tamoxifen or no adjuvant treatment. RESULTS: Exposure to 0.1%
      oxygen resulted in elevated levels of Snail protein, along with changes in
      vimentin and E-cadherin expression, and in addition increased migration of MDA-MB
      468 cells. Overexpression of Snail increased the motility of MCF-7, T-47D and MDA
      MB-231 cells, whereas silencing of the protein resulted in decreased migratory
      propensity of MCF-7, MDA-MB-468 and MDA-MB-231 cells. Moreover, nuclear Snail
      expression was associated with tumours of higher grade and proliferation rate,
      but not with disease recurrence. Interestingly, Snail negativity was associated
      with impaired tamoxifen response (P=0.048). CONCLUSIONS: Our results demonstrate
      that hypoxia induces Snail expression but generally not a migratory phenotype,
      suggesting that hypoxic cells are only partially pushed towards EMT. Furthermore,
      our study supports the link between Snail and clinically relevant features and
      treatment response.

PMID- 19844233
TI  - Enhanced sensitivity to androgen withdrawal due to overexpression of interleukin
      6 in androgen-dependent human prostate cancer LNCaP cells.
AB  - BACKGROUND: The objective of this study was to investigate the effects of
      interleukin-6 (IL-6) overexpression in androgen-dependent prostate cancer LNCaP
      cells on their phenotype under an androgen-deprived condition. METHODS: We
      established IL-6-overexpressing LNCaP (LNCaP/IL-6) by introducing the expression
      vector containing IL-6 cDNA. Changes in the phenotype in LNCaP/IL-6 were compared
      with that in LNCaP transfected with control vector alone (LNCaP/Co). RESULTS: In
      vitro, the growth of LNCaP/IL-6 was significantly inferior to that of LNCaP/Co
      under an androgen-deprived condition. Similarly, LNCaP/IL-6 tumour in nude mice
      rapidly regressed after castration; however, LNCaP/Co tumour growth was
      transiently inhibited after castration and then continuously accelerated. After
      androgen withdrawal, expression levels of phosphorylated p44/42 mitogen-activated
      protein kinase (MAPK) and Akt in LNCaP/IL-6 were markedly upregulated compared
      with those in LNCaP/Co; however, additional treatment with specific inhibitor of
      the MAPK or Akt signalling pathway significantly inhibited the growth of LNCaP/IL
      6 compared with that of LNCaP/Co. Furthermore, gene microarray analyses showed
      that androgen deprivation resulted in differential expression of genes involved
      in growth, apoptotsis and tumorigenesis between LNCaP/Co and LNCaP/IL-6.
      CONCLUSION: Excessive secretion of IL-6 by LNCaP cells in an autocrine manner may
      have a suppressive function in their growth and acquisition of androgen
      independent phenotype under an androgen-deprived condition.

PMID- 19844234
TI  - Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast
      cancer: efficacy, safety, and biomarker results from Japanese patients phase II
      studies.
AB  - BACKGROUND: HER2-positive metastatic breast cancer (MBC) relapsing after
      trastuzumab-based therapy may require continued HER2 receptor inhibition to
      control the disease and preserve the patients' quality-of-life. Efficacy and
      safety of lapatinib monotherapy was evaluated in Japanese breast cancer patients
      after trastuzumab-based therapies. METHODS: In studies, EGF100642 and EGF104911
      evaluated the efficacy and safety of oral lapatinib given 1500 mg once daily in
      patients with advanced or MBC. All patients progressed on anthracyclines and
      taxanes; HER2-positive patients had also progressed on trastuzumab. RESULTS: For
      HER2-positive tumours (n=100), objective response rate was 19.0% (95% confidence
      interval (CI): 11.8-28.1) and clinical benefit rate (CBR) was 25.0% (95% CI: 16.9
      34.7). One out of 22 HER2-negative tumour was documented as complete response
      (n=22). The median time-to-progression (TTP) in the HER2-positive and HER2
      negative groups was 13.0 and 8.0 weeks (P=0.007); median overall survival was
      58.3 and 40.0 weeks, respectively. The most frequent adverse event was diarrhoea.
      TTP and CBR were significantly associated with HER2 expression. Patients with
      tumours harbouring an H1047R PIK3CA mutation or low expression of PTEN derived
      clinical benefit from lapatinib. CONCLUSION: Lapatinib monotherapy had shown anti
      tumour activity in Japanese patients with HER2-positive MBC that relapsed after
      trastuzumab-based therapy, including those with brain metastases. Patients
      benefiting from lapatinib may have biomarker profiles differing from that
      reported for trastuzumab.

PMID- 19844235
TI  - Clinical importance of B7-H3 expression in human pancreatic cancer.
AB  - BACKGROUND: B7-H3 is a new member of the B7 ligand family and regulates T-cell
      responses in various conditions. However, the role of B7-H3 in tumour immunity is
      largely unknown. The purpose of this study was to evaluate the clinical
      significance of B7-H3 expression in human pancreatic cancer and the therapeutic
      potential for cancer immunotherapy. METHODS: We investigated B7-H3 expression in
      59 patients with pancreatic cancer by immunohistochemistry and real-time PCR.
      Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal
      antibody in vivo in a murine pancreatic cancer model. RESULTS: Tumour-related B7
      H3 expression was abundant in most human pancreatic cancer tissues and was
      significantly higher compared with that in non-cancer tissue or normal pancreas.
      Moreover, its expression was significantly more intense in cases with lymph node
      metastasis and advanced pathological stage. B7-H3 blockade promoted CD8(+) T-cell
      infiltration into the tumour and induced a substantial anti-tumour effect on
      murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3
      blockade showed a synergistic anti-tumour effect without overt toxicity.
      CONCLUSION: Our data show for the first time that B7-H3 may have a critical role
      in pancreatic cancer and provide the rationale for developing a novel cancer
      immunotherapy against this fatal disease.

PMID- 19844236
TI  - Chronic bacterial inflammation induces prostatic intraepithelial neoplasia in
      mouse prostate.
AB  - BACKGROUND: Although the aetiology of prostate cancer remains unknown, we
      hypothesised that chronic bacterial insult has a major role in prostate
      carcinogenesis. METHODS: Male C3H/HeOuJ mice, infected with phosphate-buffered
      saline or Escherichia coli bacteria, were killed at 5 days, or at 12 or 26 weeks.
      Harvested prostate tissues were evaluated for inflammatory responses and
      immunostained for neoplastic transformation markers. RESULTS: All infected mice
      developed bacterial prostatitis. Control mice had no prostate infections or
      inflammation. Mice infected for 5 days showed foci of acute inflammation with
      infiltrating neutrophils and epithelial necrotic debris in the prostatic
      glandular lumen. All mice infected for 12 weeks had evidence of chronic
      inflammation with dense inflammatory infiltrates in the stroma. The prostatic
      epithelium showed varying degrees of atypical hyperplasia with increased
      epithelial cell layers and cytological atypia. At 26 weeks, the dysplastic
      changes were more pronounced and mimicked a prostatic intraepithelial neoplasia
      and high-grade dysplasia. Prostatic glands exhibiting reactive dysplasia had a
      stronger staining for oxidative DNA damage, increased epithelial cell
      proliferation, and a decrease in androgen receptor, GSTP1, p27(Kip1), and PTEN
      expression, when compared with control prostate glands. CONCLUSION: These data
      demonstrate that chronic inflammation induces focal prostatic glandular atypia
      and suggest a potential linkage between inflammation and prostatic neoplasia.

PMID- 19844237
TI  - Mutant ubiquitin-mediated beta-secretase stability via activation of caspase-3 is
      related to beta-amyloid accumulation in ischemic striatum in rats.
AB  - Previous studies have demonstrated that ischemic stroke increases beta-amyloid
      (Abeta) production by increasing beta-secretase (BACE1) through activation of
      caspase-3, and stimulates generation of mutant ubiquitin (UBB(+1)) in rat brains.
      In this study, we examined whether caspase-3 activation participates in the
      regulation of UBB(+1) generation and UBB(+1)-mediated BACE1 stability in ischemic
      injured brains. The results showed that UBB(+1) and activated caspase-3
      immunopositive-stained cells were time dependently increased in the ipsilateral
      striatum of rat brains after middle cerebral artery occlusion. UBB(+1)
      immunopositive cells could be co-stained with caspase-3, Abeta (UBB(+1)-Abeta),
      and BACE1 (UBB(+1)-BACE1). BACE1 protein could also be pulled down by
      immunoprecipitation with UBB(+1) antibody. Z-DEVD-FMK (DEVD), a caspase-3
      inhibitor, significantly decreased the level of UBB(+1) protein and the number of
      UBB(+1)-Abeta and UBB(+1)-BACE1 double-stained cells in the ischemic striatum, as
      well as the level of UBB(+1)/BACE1 protein complex. We conclude that activation
      of caspase-3 might be upstream of UBB(+1) formation and that excessive UBB(+1)
      could bind to BACE1 and increase the stability of BACE1, thereby increasing Abeta
      in ischemic injured brains. These results suggest new biological and pathological
      effects of caspases and regulation of the ubiquitin-proteasome system in the
      brain. Our results provide new therapeutic targets to prevent further
      neurodegeneration in patients after stroke.

PMID- 19844238
TI  - Early ischemia enhances action potential-dependent, spontaneous glutamatergic
      responses in CA1 neurons.
AB  - Two types of quantal spontaneous neurotransmitter release are present in the
      nervous system, namely action potential (AP)-dependent release and AP-independent
      release. Previous studies have identified and characterized AP-independent
      release during hypoxia and ischemia. However, the relative contribution of AP
      dependent spontaneous release to the overall glutamate released during transient
      ischemia has not been quantified. Furthermore, the neuronal activity that
      mediates such release has not been identified. Using acute brain slices, we show
      that AP-dependent release constitutes approximately one-third of the overall
      glutamate-mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCs)
      measured onto hippocampal CA1 pyramidal neurons. However, during transient (2
      mins) in vitro hypoxia-hypoglycemia, large-amplitude, AP-dependent spontaneous
      release is significantly enhanced and contributes to 74% of the overall
      glutamatergic responses. This increased AP-dependent release is due to hyper
      excitability in the presynaptic CA3 neurons, which is mediated by the activity of
      NMDA receptors. Spontaneous glutamate release during ischemia can lead to
      excitotoxicity and perturbation of neural network functions.

PMID- 19844239
TI  - Sepsis-associated encephalopathy: a magnetic resonance imaging and spectroscopy
      study.
AB  - Brain dysfunction is frequently observed in sepsis as a consequence of changes in
      cerebral structure and metabolism, resulting in worse outcome and reduced life
      quality of surviving patients. However, the mechanisms of sepsis-associated
      encephalopathy development and a better characterization of this syndrome in vivo
      are lacking. Here, we used magnetic resonance imaging (MRI) techniques to assess
      brain morphology and metabolism in a murine sepsis model (cecal ligation and
      puncture, CLP). Sham-operated and CLP mice were subjected to a complete MRI
      session at baseline, 6 and 24 h after surgery. Accumulation of vasogenic edematic
      fluid at the base of the brain was observed in T(2)-weighted image at 6 and 24 h
      after CLP. Also, the water apparent diffusion coefficients in both hippocampus
      and cortex were decreased, suggesting a cytotoxic edema in brains of nonsurvival
      septic animals. Moreover, the N-acetylaspartate/choline ratio was reduced in
      brains of septic mice, indicating neuronal damage. In conclusion, noninvasive
      assessment by MRI allowed the identification of new aspects of brain damage in
      sepsis, including cytotoxic and vasogenic edema as well as neuronal damage. These
      findings highlight the potential applications of MRI techniques for the
      diagnostic and therapeutic studies in sepsis.

PMID- 19844240
TI  - In vivo validation of reconstruction-based resolution recovery for human brain
      studies.
AB  - The aim of this study was to validate in vivo the accuracy of a reconstruction
      based partial volume correction (PVC), which takes into account the point spread
      function of the imaging system. The NEMA NU2 Image Quality phantom and five
      healthy volunteers (using [(11)C]flumazenil) were scanned on both HR+ and high
      resolution research tomograph (HRRT) scanners. HR+ data were reconstructed using
      normalization and attenuation-weighted ordered subsets expectation maximization
      (NAW-OSEM) and a PVC algorithm (PVC-NAW-OSEM). HRRT data were reconstructed using
      3D ordinary Poisson OSEM (OP-OSEM) and a PVC algorithm (PVC-OP-OSEM). For
      clinical studies, parametric volume of distribution (V(T)) images were generated.
      For phantom data, good recovery was found for both OP-OSEM (0.84 to 0.97) and PVC
      OP-OSEM (0.91 to 0.98) HRRT reconstructions. In addition, for the HR+, good
      recovery was found for PVC-NAW-OSEM (0.84 to 0.94), corresponding well with OP
      OSEM. Finally, for clinical data, good correspondence was found between PVC-NAW
      OSEM and OP-OSEM-derived V(T) values (slope: 1.02+/-0.08). This study showed that
      HR+ image resolution using PVC-NAW-OSEM was comparable to that of the HRRT
      scanner. As the HRRT has a higher intrinsic resolution, this agreement validates
      reconstruction-based PVC as a means of improving the spatial resolution of the
      HR+ scanner and thereby improving the quantitative accuracy of positron emission
      tomography.

PMID- 19844241
TI  - Changes in cerebral arterial, tissue and venous oxygenation with evoked neural
      stimulation: implications for hemoglobin-based functional neuroimaging.
AB  - Little is known regarding the changes in blood oxygen tension (P(O2)) with
      changes in brain function. This work aimed to measure the blood P(O2) in surface
      arteries and veins as well as tissue with evoked somato-sensory stimulation in
      the anesthetized rat. Electrical stimulation of the forepaw induced average
      increases in blood flow of 44% as well as increases in the tissue P(O2) of 28%.
      More importantly, increases in P(O2) throughout pial arteries (resting
      diameters=59 to 129 microm) and pial veins (resting diameters=62 to 361 microm)
      were observed. The largest increases in vascular P(O2) were observed in the small
      veins (from 33 to 40 mm Hg) and small arteries (from 78 to 88 mm Hg). The changes
      in oxygen saturation (S(O2)) were calculated and the largest increases were
      observed in small veins (Delta=+11%) while its increase in small arteries was
      small (Delta=+4%). The average diameter of arterial vessels was observed to
      increase by 4 to 6% while that of veins was not observed to change with evoked
      stimulation. These findings show that the increases in arterial P(O2) contribute
      to the hyper-oxygenation of tissue and, mostly likely, also to the signal changes
      in hemoglobin-based functional imaging methods (e.g. BOLD fMRI).

PMID- 19844242
TI  - Cyclooxygenase-1 and -2 differentially modulate lipopolysaccharide-induced blood
      brain barrier disruption through matrix metalloproteinase activity.
AB  - Cyclooxygenases (COX) -1 and -2 are key regulators of innate immune responses. We
      recently demonstrated that the expression of proinflammatory cytokines and
      chemokines is reduced in COX-1 null ((-/-)), and increased in COX-2(-/-) mice
      compared with their respective wild type controls during lipopolysaccharide (LPS)
      induced innate immune activation. As chemokines are involved in leukocyte
      recruitment into the inflamed brain, we hypothesized that COX-1 and COX-2
      deletion will differentially modulate blood-brain barrier (BBB) permeability in
      response to LPS. In the present study, using quantitative magnetic resonance
      imaging, we found that LPS-induced BBB disruption was exacerbated in COX-2(-/-)
      versus COX-2(+/+) mice. In the hippocampus and cortex of LPS-treated mice, matrix
      metalloproteinase (MMP)-3 activity was significantly decreased in COX-1(-/-)
      mice, whereas in COX-2(-/-) mice the activity of both MMP-9 and MMP-3, known to
      mediate BBB breakdown, was increased. Brain mRNA expression of the leukocyte
      attracting chemokine Cxcl10, the intercellular interaction molecule Icam-1, the
      pan-leukocyte marker Cd45 was increased in COX-2(-/-) versus COX-2(+/+) mice,
      whereas Cxcl10 and Cd45 mRNA expression was decreased in COX-1(-/-) versus COX
      1(+/+) mice after LPS. Altogether, these results indicate that COX-2 activity
      modulates MMP-9 and-3 activities and is necessary to maintain BBB integrity
      during toll-like receptor 4-dependent innate immune activation.

PMID- 19844244
TI  - Thyroid gland: Pregnancy--a risk factor for thyroid surgery complications.

PMID- 19844243
TI  - Relationship of the BOLD signal with VEP for ultrashort duration visual stimuli
      (0.1 to 5 ms) in humans.
AB  - There is currently a great interest to combine electroencephalography (EEG) and
      functional magnetic resonance imaging (fMRI) to study brain function. Earlier
      studies have shown different EEG components to correlate well with the fMRI
      signal arguing for a complex relationship between both measurements. In this
      study, using separate EEG and fMRI measurements, we show that (1) 0.1 ms visual
      stimulation evokes detectable hemodynamic and visual-evoked potential (VEP)
      responses, (2) the negative VEP deflection at approximately 80 ms (N2) co-varies
      with stimulus duration/intensity such as with blood oxygenation level-dependent
      (BOLD) response; the positive deflection at approximately 120 ms (P2) does not,
      and (3) although the N2 VEP-BOLD relationship is approximately linear, deviation
      is evident at the limit of zero N2 VEP. The latter finding argues that, although
      EEG and fMRI measurements can co-vary, they reflect partially independent
      processes in the brain tissue. Finally, it is shown that the stimulus-induced
      impulse response function (IRF) at 0.1 ms and the intrinsic IRF during rest have
      different temporal dynamics, possibly due to predominance of neuromodulation
      during rest as compared with neurotransmission during stimulation. These results
      extend earlier findings regarding VEP-BOLD coupling and highlight the component-
      and context-dependency of the relationship between evoked potentials and
      hemodynamic responses.

PMID- 19844245
TI  - Adrenal gland: Hypertension during remission of childhood Cushing syndrome.

PMID- 19844246
TI  - Thyroid gland: Antithyroid therapy--best choice of drug and dose.

PMID- 19844247
TI  - Screening: Correlation of genotype and phenotype in paraganglioma.

PMID- 19844248
TI  - The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis.
AB  - Appropriate levels of phosphate in the body are maintained by the coordinated
      regulation of the bone-derived growth factor FGF23 and the membrane-bound protein
      Klotho. The endocrine actions of FGF23, in association with parathyroid hormone
      and vitamin D, mobilize sodium-phosphate cotransporters that control renal
      phosphate transport in proximal tubular epithelial cells. The availability of an
      adequate amount of Klotho is essential for FGF23 to exert its phosphaturic
      effects in the kidney. In the presence of Klotho, FGF23 activates downstream
      signaling components that influence the homeostasis of phosphate, whereas in the
      absence of this membrane protein, it is unable to exert such regulatory effects,
      as demonstrated convincingly in animal models. Several factors, including
      phosphate and vitamin D, can regulate the production of both FGF23 and Klotho and
      influence their functions. In various acquired and genetic human diseases,
      dysregulation of FGF23 and Klotho is associated with vascular and skeletal
      anomalies owing to altered phosphate turnover. In this Review, I summarize how
      the endocrine effects of bone-derived FGF23, in coordination with Klotho, can
      regulate systemic phosphate homeostasis, and how an inadequate balance of these
      molecules can lead to complications that are caused by abnormal mineral ion
      metabolism.

PMID- 19844249
TI  - Estrogen therapy: is time of initiation critical for neuroprotection?
AB  - According to the 'critical period' hypothesis, which attempts to explain the
      observed discrepancies in the studies on estrogen and cognition, estrogen therapy
      effectively decreases cognitive decline in aging women when it is initiated
      around the time of menopause but not when it is started decades later. Here, I
      review studies in which the timing of the initiation of estrogen therapy was
      provided, to determine whether their findings support the 'critical period'
      hypothesis. The vast majority of the reviewed studies support the idea that early
      but not late initiation of estrogen therapy might prevent or delay cognitive
      decline in aging women. Nevertheless, numerous design issues, such as the
      specific drugs and doses that were used, the possible effects of progestins on
      cognition, and the failure to administer neuropsychological tests of specific
      cognitive domains that are sensitive to estrogen therapy confound the extant
      literature. In view of the reanalyzes of the Women's Health Initiative's data
      that show a beneficial effect of estrogen therapy on cardiac and breast diseases
      in women aged 50-59 years, more definitive evidence is needed to confirm that the
      early initiation of estrogen therapy that is continued for a few years provides
      enduring protection against cognitive aging 15-20 years later.

PMID- 19844250
TI  - Diagnosis of insulinoma in a patient with hypoglycemia without obvious
      hyperinsulinemia.
AB  - BACKGROUND: A 41-year-old Maltese woman with a 12-month history of severe,
      morning episodes of confusion, blurred vision and sweating was referred to a
      specialist center for evaluation of fasting hypoglycemia. She was not taking
      medication and did not report any prior personal or familial history of
      endocrinopathy or other relevant pathology. INVESTIGATIONS: Measurement of plasma
      glucose, insulin, C-peptide, and beta-hydroxybutyrate concentrations during a
      prolonged supervised fast; sulfonylurea screen; CT, MRI scan and endoscopic
      ultrasonography of the pancreas; calcium stimulation test; surgical exploration
      and intra-operative ultrasonography of the pancreas. DIAGNOSIS: Insulin-secreting
      lesion (insulinoma) in the tail of the pancreas. MANAGEMENT: The tumor was
      resected with cure of symptoms.

PMID- 19844251
TI  - CB1 antagonists for obesity--what lessons have we learned from rimonabant?
AB  - When compared with other modifiable cardiovascular risk factors, such as
      hypertension, dyslipidemia and smoking, obesity remains a surprisingly puzzling
      condition to prevent and treat. The history of the development of anti-obesity
      drugs has known more defeats than even partial victories. With very few drugs on
      the market, and bad publicity related to adverse events, obesity remains an
      almost completely unmet challenge for the pharmaceutical industry. In light of
      past experience with endocannabinoid-system antagonists, such as rimonabant, we
      propose that a major paradigm shift in clinical practice might be necessary to
      justify the use of pharmacotherapy for obesity. Furthermore, we suggest that the
      criteria currently used by regulatory authorities to evaluate and approve anti
      obesity drugs should be rigorously re-examined. Finally, we discuss how
      pharmacological approaches that aim to counteract overactivity of the
      endocannabinoid system should be revisited in the future to treat visceral (intra
      abdominal) obesity and its metabolic consequences.

PMID- 19844252
TI  - Have you seen...?: Micro-managing and restraining pluripotent stem cells by MYC.
AB  - The MYC proto-oncogene, which encodes a master transcriptional regulator c-Myc
      (herein termed Myc), has a key role in stem cell (SC) pluripotency and
      tumourigenesis. Its deregulated expression contributes to cancer development and
      enhances the efficiency of reprogramming differentiated cells back to a
      pluripotent state in induced pluripotent SCs (iPSCs) that resemble embryonic SCs
      (ESCs). In addition to Myc's ability to directly regulate mRNA transcription, it
      also directly regulates microRNAs (miRNAs), thus providing an additional level of
      complexity to gene regulation. However, it had not been well understood how the
      complex network of Myc target genes contributes to pluripotency in ESCs and to
      tumourigenesis, two phenomena that are likely inter-related. In this issue of The
      EMBO Journal, Lin et al (2009) document a role of Myc in the maintenance of
      murine ESC (mESC) pluripotency through the regulation of a set of miRNAs that
      suppress differentiation, in addition to those that have been previously
      implicated in self-renewal capacity.

PMID- 19844253
TI  - Chromosome aberrations involving 10q22: report of three overlapping interstitial
      deletions and a balanced translocation disrupting C10orf11.
AB  - Interstitial deletions of chromosome band 10q22 are rare. We report on the
      characterization of three overlapping de novo 10q22 deletions by high-resolution
      array comparative genomic hybridization in three unrelated patients. Patient 1
      had a 7.9 Mb deletion in 10q21.3-q22.2 and suffered from severe feeding problems,
      facial dysmorphisms and profound mental retardation. Patients 2 and 3 had nearly
      identical deletions of 3.2 and 3.6 Mb, the proximal breakpoints of which were
      located at an identical low-copy repeat. Both patients were mentally retarded;
      patient 3 also suffered from growth retardation and hypotonia. We also report on
      the results of breakpoint analysis by array painting in a mentally retarded
      patient with a balanced chromosome translocation 46,XY,t(10;13)(q22;p13)dn. The
      breakpoint in 10q22 was found to disrupt C10orf11, a brain-expressed gene in the
      common deleted interval of patients 1-3. This finding suggests that
      haploinsufficiency of C10orf11 contributes to the cognitive defects in 10q22
      deletion patients.

PMID- 19844254
TI  - Familial interstitial Xq27.3q28 duplication encompassing the FMR1 gene but not
      the MECP2 gene causes a new syndromic mental retardation condition.
AB  - X-linked mental retardation is a common disorder that accounts for 5-10% of cases
      of mental retardation in males. Fragile X syndrome is the most common form
      resulting from a loss of expression of the FMR1 gene. On the other hand, partial
      duplication of the long arm of the X chromosome is uncommon. It leads to
      functional disomy of the corresponding genes and has been reported in several
      cases of mental retardation in males. In this study, we report on the clinical
      and genetic characterization of a new X-linked mental retardation syndrome
      characterized by short stature, hypogonadism and facial dysmorphism, and show
      that this syndrome is caused by a small Xq27.3q28 interstitial duplication
      encompassing the FMR1 gene. This family broadens the phenotypic spectrum of FMR1
      anomalies in an unexpected manner, and we suggest that this condition may
      represent the fragile X syndrome "contre-type".

PMID- 19844255
TI  - Fine mapping and association studies of a high-density lipoprotein cholesterol
      linkage region on chromosome 16 in French-Canadian subjects.
AB  - Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent
      risk factor for cardiovascular disease. To identify novel genetic variants that
      contribute to HDL-C, we performed genome-wide scans and quantitative association
      studies in two study samples: a Quebec-wide study consisting of 11
      multigenerational families and a study of 61 families from the Saguenay-Lac St
      Jean (SLSJ) region of Quebec. The heritability of HDL-C in these study samples
      was 0.73 and 0.49, respectively. Variance components linkage methods identified a
      LOD score of 2.61 at 98 cM near the marker D16S515 in Quebec-wide families and an
      LOD score of 2.96 at 86 cM near the marker D16S2624 in SLSJ families. In the
      Quebec-wide sample, four families showed segregation over a 25.5-cM (18 Mb)
      region, which was further reduced to 6.6 Mb with additional markers. The coding
      regions of all genes within this region were sequenced. A missense variant in
      CHST6 segregated in four families and, with additional families, we observed a P
      value of 0.015 for this variant. However, an association study of this single
      nucleotide polymorphism (SNP) in unrelated Quebec-wide samples was not
      significant. We also identified an SNP (rs11646677) in the same region, which was
      significantly associated with a low HDL-C (P=0.016) in the SLSJ study sample. In
      addition, RT-PCR results from cultured cells showed a significant difference in
      the expression of CHST6 and KIAA1576, another gene in the region. Our data
      constitute additional evidence for a locus on chromosome 16q23-24 that affects
      HDL-C levels in two independent French-Canadian studies.

PMID- 19844256
TI  - Clinical spectrum associated with recurrent genomic rearrangements in chromosome
      17q12.
AB  - Deletions in chromosome 17q12 encompassing the HNF1 beta gene cause cystic renal
      disease and maturity onset diabetes of the young, and have been recently
      described as the first recurrent genomic deletion leading to diabetes. Earlier
      reports of patients with this microdeletion syndrome have suggested an absence of
      cognitive impairment, differentiating it from most other contiguous gene deletion
      syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized
      to be associated with an increased risk of epilepsy and mental retardation. We
      conducted a detailed clinical and molecular characterization of four patients
      with a deletion and five patients with a reciprocal duplication of this region.
      Our patients with deletion of 17q12 presented with cognitive impairment, cystic
      renal disease, seizures, and structural abnormalities of the brain. Patients with
      reciprocal duplications manifest with cognitive impairment and behavioral
      abnormalities, but not with seizures. Our findings expand the phenotypic spectrum
      associated with rearrangements of 17q12 and show that cognitive impairment is a
      part of the phenotype of individuals with deletions of 17q12.

PMID- 19844257
TI  - Long time no see: the Type and Contre-type concept.

PMID- 19844258
TI  - Polymorphisms in TLR4 and TLR2 genes, cytokine production and survival in rural
      Ghana.
AB  - Toll-like receptors (TLRs) are involved in the induction of an adequate immune
      response on infection. We hypothesized that genetic variation in TLR4 and TLR2
      genes could influence this response and lead to variability in cytokine
      production and survival. We tested this hypothesis in 4292 participants who were
      followed up for all-cause mortality for 6 years and live under adverse
      environmental conditions in the Upper-East region of Ghana, where malaria is
      endemic. In 605 participants, tumor necrosis factor-alpha and interleukin-10
      (IL10) production, after stimulation with lipopolysaccharide and zymosan, was
      measured. In addition, 34 single-nucleotide polymorphisms (SNPs) in TLR4 and 12
      SNPs in TLR2 were genotyped and tested for association with cytokine production,
      malaria infection and mortality. In this comprehensive gene-wide approach, we
      identified novel SNPs in the TLR4 gene that influence cytokine production. From
      the analyzed SNPs, rs7860896 associated the strongest with IL10 production
      (P=0.0005). None of the SNPs in this study associated with malaria or overall
      mortality risks. In conclusion, we demonstrate that genetic variation within the
      TLR4 gene influences cytokine production capacity, but in an endemic area does
      not influence the susceptibility to malaria infection or mortality.

PMID- 19844259
TI  - Drawing the history of the Hutterite population on a genetic landscape: inference
      from Y-chromosome and mtDNA genotypes.
AB  - Although the North American Hutterites trace their origins to South Tyrol, no
      attempts have been made to examine the genetic migration history of the
      Hutterites before emigrating to the United States in the 1870s. To investigate
      this, we studied 9 microsatellite loci and 11 unique event polymorphism (UEP)
      markers on the Y-chromosome, the hypervariable region I (HVRI) of the
      mitochondrial DNA (mtDNA), as well as the complete mtDNA genome of Hutterite and
      South Tyrolean samples. Only 6 out of 14 Y-chromosome UEP+microsatellite
      haplotypes and 3 out of 11 mitochondrial haplotypes that were present in the
      Hutterites were also present in the South Tyrolean population. The phylogenetic
      relationships inferred from Y-chromosome and mtDNA databases show that the
      Hutterites have a unique genetic background related to a similar extent to
      central and eastern European populations. An admixture analysis indicates,
      however, a relatively high genetic contribution of central European populations
      to the Hutterite gene pool. These results are consistent with historical records
      on Hutterite migrations and demographic history. In addition, our data reveal
      similar numbers of Y and mitochondrial haplotypes in Hutterite male and female
      founders, respectively. The Hutterite male and female gene pools are similar with
      respect to genetic diversity and genetic distance measures and comparable with
      respect to their origins, suggesting a similar evolutionary history.

PMID- 19844260
TI  - A syndrome of short stature, microcephaly and speech delay is associated with
      duplications reciprocal to the common Sotos syndrome deletion.
AB  - Genomic rearrangements are an increasingly recognized mechanism of human
      phenotypic variation and susceptibility to disease. Sotos syndrome is
      characterized by overgrowth, macrocephaly, developmental delay and advanced
      osseous maturation. Haploinsufficiency of NSD1, caused by inactivating point
      mutations or deletion copy number variants, is the only known cause of Sotos
      syndrome. A recurrent 2 Mb deletion has been described with variable frequency in
      different populations. In this study, we report two individuals of different
      ethnic and geographical backgrounds, with duplications reciprocal to the common
      Sotos syndrome deletion. Our findings provide evidence for the existence of a
      novel syndrome of short stature, microcephaly, delayed bone development, speech
      delay and mild or absent facial dysmorphism. The phenotype is remarkably opposite
      to that of Sotos syndrome, suggesting a role for NSD1 in the regulation of
      somatic growth in humans.

PMID- 19844261
TI  - Identification and characterization of seven novel mutations of elastin gene in a
      cohort of patients affected by supravalvular aortic stenosis.
AB  - Supravalvular aortic stenosis (SVAS) is a congenital narrowing of the ascending
      aorta, which can occur sporadically as an autosomal dominant condition or as one
      component of the Williams-Beuren syndrome, a complex developmental genomic
      disorder associated with cardiovascular, neurobehavioral, craniofacial, and
      metabolic abnormalities, caused by a microdeletion at 7q11.23. We report the
      identification of seven novel mutations within the elastin gene in 31 familial
      and sporadic cases of nonsyndromic SVAS. Five are frameshift mutations within the
      coding region of the ELN gene that result in premature stop codons (PTCs); the
      other two mutations abolish the donor splice site of introns 3 and 28,
      respectively, and are predicted to alter splicing efficiency resulting in the
      generation of a PTC within the same introns of the gene. In vitro analysis using
      minigenes and cycloheximide showed that some selected frameshift mutant alleles
      are substrates of nonsense-mediated mRNA decay (NMD), confirming that the
      functional haploinsufficiency of the ELN gene is the main pathomechanism
      underlying SVAS. Interestingly, molecular analysis on patient fibroblasts showed
      that the c.2044+5G>C mutant allele encodes for an aberrant shorter form of the
      elastin polypeptide that may hamper the normal assembly of elastin fibers in a
      dominant-negative manner.

PMID- 19844262
TI  - Genetic profile for five common variants associated with age-related macular
      degeneration in densely affected families: a novel analytic approach.
AB  - About 40% of the genetic variance of age-related macular degeneration (AMD) can
      be explained by a common variation at five common single-nucleotide polymorphisms
      (SNPs). We evaluated the degree to which these known variants explain the
      clustering of AMD in a group of densely affected families. We sought to determine
      whether the actual number of risk alleles at the five variants in densely
      affected families matched the expected number. Using data from 322 families with
      AMD, we used a simulation strategy to generate comparison groups of families and
      determined whether their genetic profile at the known AMD risk loci differed from
      the observed genetic profile, given the density of disease observed. Overall, the
      genotypic loads for the five SNPs in the families did not deviate significantly
      from the genotypic loads predicted by the simulation. However, for a subset of
      densely affected families, the mean genotypic load in the families was
      significantly lower than the expected load determined from the simulation. Given
      that these densely affected families may harbor rare, more penetrant variants for
      AMD, linkage analyses and resequencing targeting these families may be an
      effective approach to finding additional implicated genes.

PMID- 19844263
TI  - Genomic landscape of positive natural selection in Northern European populations.
AB  - Analyzing genetic variation of human populations for detecting loci that have
      been affected by positive natural selection is important for understanding
      adaptive history and phenotypic variation in humans. In this study, we analyzed
      recent positive selection in Northern Europe from genome-wide data sets of 250
      000 and 500 000 single-nucleotide polymorphisms (SNPs) in a total of 999
      individuals from Great Britain, Northern Germany, Eastern and Western Finland,
      and Sweden. Coalescent simulations were used for demonstrating that the
      integrated haplotype score (iHS) and long-range haplotype (LRH) statistics have
      sufficient power in genome-wide data sets of different sample sizes and SNP
      densities. Furthermore, the behavior of the F(ST) statistic in closely related
      populations was characterized by allele frequency simulations. In the analysis of
      the North European data set, 60 regions in the genome showed strong signs of
      recent positive selection. Out of these, 21 regions have not been discovered in
      previous scans, and many contain genes with interesting functions (eg, RAB38,
      INFG, NOS1AP, and APOE). In the putatively selected regions, we observed a
      statistically significant overrepresentation of genetic association with complex
      disease, which emphasizes the importance of the analysis of positive selection in
      understanding the evolution of human disease. Altogether, this study demonstrates
      the potential of genome-wide data sets to discover loci that lie behind
      evolutionary adaptation in different human populations.

PMID- 19844264
TI  - European admixture on the Micronesian island of Kosrae: lessons from complete
      genetic information.
AB  - The architecture of natural variation present in a contemporary population is a
      result of multiple population genetic forces, including population bottleneck and
      expansion, selection, drift, and admixture. We seek to untangle the contribution
      of admixture to genetic diversity on the Micronesian island of Kosrae. Toward
      this goal, we used a complete genetic approach by combining a dense genome-wide
      map of 100,000 single-nucleotide polymorphisms (SNPs) with data from uniparental
      markers from the mitochondrial genome and the nonrecombining portion of the Y
      chromosome. These markers were typed in approximately 3200 individuals from
      Kosrae, representing 80% of the adult population of the island. We developed
      novel software that uses SNP data to delineate ancestry for individual segments
      of the genome. Through this analysis, we determined that 39% of Kosraens have
      some European ancestry. However, the vast majority of admixed individuals (77%)
      have European alleles spanning less than 10% of their genomes. Data from
      uniparental markers show most of this admixture to be male, introduced in the
      late nineteenth century. Furthermore, pedigree analysis shows that the majority
      of European admixture on Kosrae is because of the contribution of one individual.
      This approach shows the benefit of combining information from autosomal and
      uniparental polymorphisms and provides new methodology for determining ancestry
      in a population.

PMID- 19844265
TI  - Array-based comparative genomic hybridization identifies a high frequency of copy
      number variations in patients with syndromic overgrowth.
AB  - Overgrowth syndromes are a heterogeneous group of conditions including endocrine
      hormone disorders, several genetic syndromes and other disorders with unknown
      etiopathogenesis. Among genetic causes, chromosomal deletions and duplications
      such as dup(4)(p16.3), dup(15)(q26qter), del(9)(q22.32q22.33), del(22)(q13) and
      del(5)(q35) have been identified in patients with overgrowth. Most of them,
      however, remain undetectable using banding karyotype analysis. In this study, we
      report on the analysis using a 1-Mb resolution array-based comparative genomic
      hybridization (CGH) of 93 patients with either a recognizable overgrowth
      condition (ie, Sotos syndrome or Weaver syndrome) or an unclassified overgrowth
      syndrome. Five clinically relevant imbalances (three duplications and two
      deletions) were identified and the pathogenicity of two additional anomalies (one
      duplication and one deletion) is discussed. Altered segments ranged in size from
      0.32 to 18.2 Mb, and no recurrent abnormality was identified. These results show
      that array-CGH provides a high diagnostic yield in patients with overgrowth
      syndromes and point to novel chromosomal regions associated with these
      conditions. Although chromosomal deletions are usually associated with growth
      retardation, we found that the majority of the imbalances detected in our
      patients are duplications. Besides their importance for diagnosis and genetic
      counseling, our results may allow to delineate new contiguous gene syndromes
      associated with overgrowth, pointing to new genes, the deregulation of which may
      be responsible for growth defect.

PMID- 19844266
TI  - Large-scale SNP genotyping in crosses between outbred lines: how useful is it?
AB  - Although genome-wide association (GWA) studies are not worth the effort in
      crosses between inbred lines, many crosses are actually made up of divergent yet
      outbred populations. Despite its relevance, however, this experimental setting
      has not been studied at a time when SNP microarrays are available in many
      species. To assess whether GWA can be useful in this setting, we performed
      combined coalescence--gene dropping simulations. We studied the influence of
      marker density, QTL effect and QTL allele frequency on power, false discovery
      rate (FDR) and accuracy. Our results suggest that GWA in outbred F(2) crosses is
      useful, especially in large populations. Under these circumstances, accuracy
      increased and FDR decreased as compared with classical linkage analysis. However,
      current SNP densities (in the order of 30-60 K SNPs/genome or equivalent to 10-20
      SNPs per cM) may not be much better than linkage analysis and higher SNP
      densities may be required. SNP ascertainment had an important effect; the best
      option was to select SNPs as uniformly as possible without setting any
      restriction on allele frequency. Using only SNPs with fixed alternative alleles
      in each breed controlled false positive rate but was not useful to detect
      variability within lines. Finally, the most significant SNP was not necessarily
      the closest to the causal SNP, although the closest SNPs were usually above the
      significance threshold; thus, it is prudent to follow-up significant signals
      located in regions of interest even if they do not correspond to absolute maxima.

PMID- 19844267
TI  - What's your poison?

PMID- 19844268
TI  - High gene flow due to pelagic larval dispersal among South Pacific archipelagos
      in two amphidromous gastropods (Neritomorpha: Neritidae).
AB  - The freshwater stream fauna of tropical oceanic islands is dominated by
      amphidromous species, whose larvae are transported to the ocean and develop in
      the plankton before recruiting back to freshwater habitat as juveniles. Because
      stream habitat is relatively scarce and unstable on oceanic islands, this life
      history would seem to favor either the retention of larvae to their natal
      streams, or the ability to delay metamorphosis until new habitat is encountered.
      To distinguish between these hypotheses, we used population genetic methods to
      estimate larval dispersal among five South Pacific archipelagos in two
      amphidromous species of Neritid gastropod (Neritina canalis and Neripteron
      dilatatus). Sequence data from mitochondrial cytochrome oxidase I (COI) revealed
      that neither species is genetically structured throughout the Western Pacific,
      suggesting that their larvae have a pelagic larval duration (PLD) of at least 8
      weeks, longer than many marine species. In addition, the two species have
      recently colonized isolated Central Pacific archipelagos in three independent
      events. Since colonization, there has been little or no gene flow between the
      Western and Central Pacific archipelagos in N. canalis, and high levels of gene
      flow across the same region in N. dilatatus. Both species show departures from
      neutrality and recent dates for colonization of the Central Pacific archipelagos,
      which is consistent with frequent extinction and recolonization of stream
      populations in this area. Similar results from other amphidromous species suggest
      that unstable freshwater habitats promote long-distance dispersal capabilities.

PMID- 19844269
TI  - Linkage disequilibrium in wild French grapevine, Vitis vinifera L. subsp.
      silvestris.
AB  - Association mapping based on linkage disequilibrium (LD) can provide high
      resolution for whole-genome mapping of genes underlying phenotypic variation.
      This field has received considerable attention over the last decade. We present
      here the first characterization of LD in wild French grapevine, Vitis vinifera L.
      subsp. silvestris. To assess the pattern and extent of LD, we used a sample of 85
      plants from southern France and 36 microsatellite markers distributed over 5
      linkage groups. LD was evaluated with independence tests and multiallelic r(2),
      using both unphased genotypic data and reconstructed haplotypic data. LD decayed
      rapidly, with r(2) values decreasing to 0.1 within 2.7 cM for genotypic data and
      within 1.4 cM for haplotypic data. Compared to the results of a previous study on
      cultivated grapevine subsp. sativa, where significant LD was found up to 16.8 cM,
      LD in subsp. silvestris was no longer significant past 1.4 cM. LD was therefore
      12 times further extended in cultivated than wild grapevine, even though LD in
      wild grapevine seemed to extend slightly further than in wild relatives of other
      crops. Domestication bottlenecks and vegetative propagation are the primary
      factors responsible for this difference between cultivated and wild grapevine.
      The rapid decay of LD observed in this study seems promising for future
      association mapping studies of functional variation in wild V. vinifera
      grapevine.

PMID- 19844270
TI  - Long-term conservation vs high sequence divergence: the case of an
      extraordinarily old satellite DNA in bivalve mollusks.
AB  - The ubiquity of satellite DNA (satDNA) sequences has raised much controversy over
      the abundance of divergent monomer variants and the long-time nucleotide sequence
      stability observed for many satDNA families. In this work, we describe the satDNA
      BIV160, characterized in nine species of the three main bivalve clades
      (Protobranchia, Pteriomorphia and Heteroconchia). BIV160 monomers are similar in
      repeat size and nucleotide sequence to satDNAs described earlier in oysters and
      in the clam Donax trunculus. The broad distribution of BIV160 satDNA indicates
      that similar variants existed in the ancestral bivalve species that lived about
      540 million years ago; this makes BIV160 the most ancient satDNA described so
      far. In the species examined, monomer variants are distributed in quite a complex
      pattern. This pattern includes (i) species characterized by a specific group of
      variants, (ii) species that share distinct group(s) of variants and (iii) species
      with both specific and shared types. The evolutionary scenario suggested by these
      data reconciles sequence uniformity in homogenization-maintained satDNA arrays
      with the genomic richness of divergent monomer variants formed by diversification
      of the same ancestral satDNA sequence. Diversified repeats can continue to evolve
      in a non-concerted manner and behave as independent amplification-contraction
      units in the framework of a 'library of satDNA variants' representing a permanent
      source of monomers that can be amplified into novel homogeneous satDNA arrays. On
      the whole, diversification of satDNA monomers and copy number fluctuations
      provide a highly dynamic genomic environment able to form and displace satDNA
      sequence variants rapidly in evolution.

PMID- 19844272
TI  - [Communication between general practitioners and pharmacies].

PMID- 19844271
TI  - [Exit].

PMID- 19844273
TI  - [Is a woman's life less valuable than a man's?].

PMID- 19844274
TI  - [Communication about prescription interventions between pharmacists and general
      practitioners].
AB  - BACKGROUND: Pharmacists intervene on about 2 % of prescriptions dispensed in
      Norwegian community pharmacies. The aim of this study was to explore how general
      practitioners (GPs) and community pharmacists communicate and document
      prescription interventions, and to discuss what both professions consider to be
      best practice. MATERIAL AND METHODS: Five GPs, five community pharmacists and two
      medical secretaries were recruited, from two regions in Norway, to form two focus
      groups. The groups were invited to discuss 12 real examples of prescription
      interventions (from a former study of pharmacy practice) from six intervention
      categories. Statements from the focus groups were analyzed and recurrent themes
      identified. RESULTS: The GPs and pharmacists described varying management of the
      pharmacists' prescription interventions. Both expected the other profession to
      file these interventions and would only file a selection themselves. Correction
      of prescription interventions was not a well-established functionality of the
      GPs' electronic medical record systems. Lack of guidelines caused individual
      variations in both GP and pharmacist handling of such interventions. In general,
      the pharmacists prioritized to contact GPs for the clinically relevant
      interventions. GPs wanted more feedback than that provided by the pharmacists.
      INTERPRETATION: Joint guidelines for use in pharmacies and GP surgeries, are
      needed on communication, documentation, and priorities of prescription
      interventions. IT-software should be developed to facilitate real-time
      communication between the parties.

PMID- 19844275
TI  - [Frequency of forensic autopsies after deaths in road traffic accidents].
AB  - BACKGROUND: In 2007, 224 persons died in road traffic accidents in Norway.
      According to the instruction for prosecution, the police should request forensic
      autopsy in such deaths. The police's adherence to this instruction varies. The
      aim of this study was to document enforcement of the instruction for prosecution
      among police districts in two Norwegian counties (North and South Trondelag).
      MATERIAL AND METHOD: Data from forensic autopsies of deaths in road traffic
      accidents performed at The Department of Pathology and Medical Genetics at St.
      Olavs Hospital were compared with data from similar deaths in the two counties
      registered in The Cause of Deaths Statistics in Statistics Norway for the time
      period 1996-2005. RESULTS: 249 persons died in road traffic accidents in the two
      counties in the time period assessed; forensic autopsies were performed on 157
      (63 %) of them. The forensic autopsy rate decreased from 69 % in the first 5-year
      period to 57 % in the second period. The largest decrease was in North Trondelag
      where the rate dropped from 62 % to 38 %. Drivers of motorized vehicles were to a
      larger extent autopsied than other road-users; victims of motorcycle accidents
      were autopsied to a lesser extent than those of car accidents and other types of
      road traffic accidents. INTERPRETATION: The reduced frequency of autopsy and
      differences in request practice between police districts may be explained by
      economical circumstances, different understanding of the importance of forensic
      autopsies and different interpretation of the instruction for prosecution. It is
      not known whether there were important differences between those who were
      autopsied and those who were not.

PMID- 19844276
TI  - [Symptoms and diagnosis of coronary heart disease in women].
AB  - BACKGROUND: Coronary heart disease in women is different from that in men with
      respect to symptoms, clinical presentation, value of the diagnostic tests and
      response to treatment. The article presents a review of symptoms and diagnostics
      of coronary heart disease in women and discusses the diagnostic procedures that
      are available. MATERIAL AND METHODS: The review is based on literature identified
      through a non-systematic search of PubMed. RESULTS: In general, myocardial
      infarction hits women about ten years later than men, but women with risk factors
      loose their sex advantage. Women with coronary disease are less likely to
      experience chest pain than men and may have less specific symptoms. Traditional
      non-invasive diagnostic investigations are less accurate than in men. Women with
      angina or myocardial infarction also have a lower prevalence of significant
      stenoses in coronary angiography, and atherosclerosis seems to be more diffuse
      than in men. This renders the diagnostic approach more difficult. Coronary CT
      angiography is a promising diagnostic technique, but few women have been included
      in studies of the method's accuracy, and the radiation dose is still relatively
      high. INTERPRETATION: We recommend a strategy that emphasizes risk stratification
      of patients, and thereafter identification of patients in need of further
      invasive testing. New techniques are needed to identify coronary heart disease in
      women.

PMID- 19844277
TI  - [Lung cancer in smokers and never-smokers].
AB  - BACKGROUND: Lung cancer is the most frequent cancer-related cause of death for
      both sexes. Smoking is the cause of most cases, but estimates show that 15-20 %
      of cases in the western world are not associated with tobacco. Recent evidence -
      based on molecular and clinical studies - indicate that lung cancer in patients
      who have never smoked has certain characteristics that are different from those
      in patients who smoke. In this article we describe some of these characteristics.
      MATERIAL AND METHODS: The present paper is based on literature identified through
      non-systematic searches in PubMed. RESULTS: Lung cancer in never-smokers is
      estimated to be the seventh most frequent cancer type on a global basis. A number
      of molecular and clinical characteristics differ between lung cancer related to
      tobacco use and those not related to tobacco use. 62 % of lung cancers among
      never-smokers are adenocarcinomas and 18 % are squamous cell carcinomas, while
      corresponding numbers among patients who smoke are 19 % and 53 %. The K-Ras-gene
      is often mutated in tumours from smokers, but seldom in tumours from non-smokers;
      whereas the EGFR-gene is mutated in tumours from non-smokers, and not in smokers.
      Also, age and sex distribution, therapy response and prognosis are shown to
      differ between the groups. INTERPRETATION: Lung cancer in never-smokers should
      probably be regarded as a different disease-entity than smoking-induced lung
      cancer. This could impact prognosis as well as treatment.

PMID- 19844278
TI  - [Maggot therapy in wound management].
AB  - BACKGROUND: Maggots' ability to prevent infections and promote wound healing has
      been known since the 19th century. Increasing problems with treatment-resistant
      wounds and antibiotic-resistant bacteria has aroused interest in maggot therapy.
      MATERIAL AND METHODS: Literature on maggot therapy - identified through a non
      systematic search of Pubmed - was reviewed. RESULTS: Maggot therapy is the
      medical use of disinfected fly larvae (usually the larvae of Lucilia sericata) in
      treatment of wounds resistant to conventional treatment. The maggots work through
      three mechanisms of action; they debride wounds by dissolving necrotic tissue,
      clean wounds by killing bacteria and promote wound healing. The larvae have a
      broad antibacterial action against Gram-negative and Gram-positive bacteria,
      including MRSA. Maggot therapy is used to debride a number of complicated skin
      and soft tissue wounds - e.g.. pressure ulcers, venous stasis ulcers,
      neurovascular ulcers, traumatic wounds and burns - but also as a treatment for
      osteomyelitis. Large controlled clinical trials have not been performed. Maggot
      therapy has not been associated with serious side effects. INTERPRETATION: Maggot
      therapy seems to be an effective and environmentally friendly treatment of
      complicated necrotic wounds that are resistant to conventional treatment. Maggot
      therapy should also be considered in earlier stages of treatment.

PMID- 19844279
TI  - [Quality of referrals from general practitioners to medical polyclinics].

PMID- 19844280
TI  - [Tobacco consumption among men and women 1927-2007].
AB  - BACKGROUND: After 100 years of mass consumption of cigarettes, the smoking
      epidemic is on the verge of a historic decline in Norway. The article shows the
      number of smokers and tobacco consumption among men and women from 1927 to 2007.
      MATERIAL AND METHODS: The total consumption of tobacco was estimated by adding up
      registered and unregistered sales. Data were collected from the Directorate of
      Customs and Excise and the tobacco industry. Sex-specific consumption was
      calculated from information on proportion of smokers and daily consumption (self
      reported), excerpted from time series of representative cross-sectional surveys.
      RESULTS: About 800,000 men - more men than women - smoked in the early 1960s, but
      the annual consumption of cigarettes per adult male reached its peak (2.8 kg) in
      the mid-1970s. The number of smokers among men has been halved since then and
      consumption reduced to 1.5 kg per adult male in 2007. Consumption peaked among
      women in about 1990, but stopped at 1.8 kg. The number of female smokers has only
      been reduced by about 150 000 individuals since it culminated at around 600,000
      in the early 1970s. Men smoked more than 70 % of the cigarettes consumed from
      1927 to 2007. INTERPRETATION: The tobacco epidemic has affected men more than
      women. After 1995 a sex convergence has been observed.

PMID- 19844281
TI  - [Thiazides--a first choice against high blood pressure].
AB  - Thiazide therapy of hypertension has increased substantially in Norway during the
      last decade. This is caused partly by changed dosage recommendations - which has
      led to fewer side effects - and an increased awareness of the cost associated
      with hypertension therapy. Thiazide therapy is among one of the most cost
      effective drug therapies within preventive cardiology. Prevention of primary
      endpoints such as cerebrovascular disease, cardiovascular mortality and
      congestive heart failure is well documented.

PMID- 19844282
TI  - [50-year-old woman with elevated haemoglobin and iron deficiency].
AB  - BACKGROUND: Elevated haemoglobin and erythrocytosis are frequent causes for
      investigation. MATERIAL AND METHODS: A 50-year-old woman with elevated
      haemoglobin and erythrocytosis was referred to our hospital for investigation.
      RESULTS AND INTERPRETATION: She had elevated serum erythropoietin and iron
      deficiency. Mutational status of the JAK2 gene was negative with respect to
      polycythemia vera, and no secondary reasons for polycythemia - including tumours 
      were revealed. A bone marrow biopsy and bone marrow smear showed a moderately
      increased number of lambda- positive monoclonal plasma cells, and small amounts
      of lambda light chains were detected in the urine. Serum electrophoreses showed
      no gammopathy. The reason for her elevated haemoglobin could be an erythropoietin
      producing tumour or an idiopathic erythrocytosis based on a mutation in exon 12
      of the JAK2 gene. Investigation of her plasma cells revealed a 10-fold increase
      in erythropoietin mRNA expression, indicating the reason for her elevated serum
      erythropoietin and haemoglobin values.

PMID- 19844283
TI  - [Is high hemoglobin level dangerous?].

PMID- 19844284
TI  - [Circadian rhythm sleep disorders].
AB  - BACKGROUND: Circadian rhythm sleep disorders often lead to sleepiness and
      insomnia. These disorders are characterized by a misalignment between the
      intrinsic circadian rhythm and the external social and physical environment.
      MATERIAL AND METHOD: This review is based on the authors' research and clinical
      experience and on articles identified by non-systematic searches in Pubmed and
      ISI Web of Knowledge. RESULTS: Circadian rhythm sleep disorders are categorized
      into six subtypes: Delayed sleep-phase disorder, advanced sleep-phase disorder,
      irregular sleep-wake rhythm, free-running disorder, jet-lag and shift work
      disorder. By administering light and/or melatonin at appropriate times in
      accordance with the phase response curves of light and melatonin, most of the
      circadian rhythm sleep disorders can be treated effectively. The documented
      effects of these interventions are good, but well-controlled studies with long
      term follow-up are needed. INTERPRETATION: The best-documented approaches to
      treating circadian rhythm sleep disorders are light and melatonin; physicians can
      easily administer both treatments.

PMID- 19844285
TI  - [Sleep-related movement disorders].
AB  - BACKGROUND: Restless legs syndrome is a common cause of sleep problems; the
      condition is often associated with periodic limb movement during sleep. The
      syndrome is probably under-diagnosed and under-treated. MATERIAL AND METHODS: The
      article is based on literature identified through a search in PubMed, a review of
      international recommendations and our own clinical experience. RESULTS: The
      restless leg syndrome is common, with a prevalence of about 10 %. Many of these
      patients are affected by sleep disturbances and have periodic limb movement
      during sleep (PLMS). Restless legs and the associated sleep disturbances can be
      effectively treated with dopaminagonists. Because of the augmentation risk, the
      lowest necessary dose should be maintained. PLMS also occurs in other sleep
      disorders. Periodic limb movement disorder (PLMD) is defined as PLMS combined
      with sleep disturbances and/or sleepiness during daytime without a known cause.
      The clinical relevance of PLMD for sleep disturbances is not clear.
      INTERPRETATION: The restless legs syndrome is a common cause of sleep
      disturbance; good treatment options are available.

PMID- 19844286
TI  - [Parasomnias].
AB  - BACKGROUND: Parasomnias are undesirable experiences or motoric phenomena that
      occur in association with sleep. We have described characteristics of parasomnia
      subtypes. MATERIAL AND METHOD: This review is based on the authors' research and
      clinical experience, and articles identified by non-systematic searches of
      Pubmed. RESULTS: Parasomnias are categorized into disorders of arousal (non-REM
      sleep parasomnias), e.g. sleepwalking, sleep terrors and confusional arousals,
      parasomnias associated with REM sleep, e.g. nightmare disorder, REM sleep
      behaviour disorder and recurrent isolated sleep paralysis, and other parasomnias,
      e.g. sleep-related groaning, exploding head syndrome, sleep-related
      hallucinations and sleep-related eating disorder. Prevalences for the subtypes
      vary. INTERPRETATION: Most parasomnias are especially common in children. Drug
      treatment is seldom necessary, but may be indicated in severe cases.

PMID- 19844287
TI  - [Vitamin D status and disease--hasty conclusions?].

PMID- 19844289
TI  - [Ovary--not prostate].

PMID- 19844290
TI  - [The ram and the oat bag].

PMID- 19844291
TI  - [Zero hour--the poet Dorothy Parker and insomnia].
AB  - Dorothy Parker (1893-1967) was an American poet and author, known for her wicked
      wittiness, tender verses and sharp eye for the foibles of modern urban humans.
      She writes about her insomnia, and the time of day when despair is greatest and
      self-esteem lowest.

PMID- 19844292
TI  - [Miraculous cure in Lourdes?].

PMID- 19844293
TI  - [Army doctor accused of falsifying data].

PMID- 19844295
TI  - Design of a single-multimode-single-mode filter demodulator for fiber Bragg
      grating sensors assisted by mode observation.
AB  - We propose a simple analysis of a single-multimode-single-mode fiber (SMSMF)
      filter by observing the excited modes in multimode fiber (MMF). The method is
      used to design a SMSMF filter demodulator for fiber Bragg grating sensors, and a
      corresponding demodulation system is created. The static and dynamic measurements
      based on the system are given to prove the feasibility of the intensity
      demodulator.

PMID- 19844296
TI  - Design and fabrication of a spatial light modulator using thermally tunable
      grating and a thin-film heater.
AB  - We propose the application of a thermally tunable grating as a spatial light
      modulator. The grooves of a square-well grating are filled with a liquid whose
      refractive index depends on temperature. The variation of optical characteristics
      of such a grating with respect to temperature is investigated theoretically and
      also by simulation and experiment. A thin-film heater is then used as a heat
      source. The relation between intensity of the first order of diffraction versus
      power consumption of the thin-film heater is investigated. Finally, a thin-film
      heater with a desired pattern is placed at the surface of the grating to
      fabricate spatial light modulator. By applying electrical current to different
      elements of the thin-film heater, the fabricated device can project a desired
      pattern on a screen using a 4f imaging system. The restrictions of such a device
      are discussed and another structure is proposed and discussed by numerical
      calculations to increase the ability of the device.

PMID- 19844297
TI  - Light scattering calculations exploring sensitivity of depolarization ratio to
      shape changes. II. Single rod-shaped vegetative bacteria in air.
AB  - In article I of this series, calculations and graphs of the depolarization ratio,
      D(Theta,lambda)=1-<S22>/<S11>, for light scattered from an ensemble of single
      aerosolized Bacillus spores using the discrete dipole approximation (DDA)
      (sometimes also called the coupled dipole approximation) were presented. The Sij
      in these papers denote the appropriate Mueller matrix elements. We compare graphs
      for different size parameters for both D(Theta,lambda) and the ratio
      R34(Theta,lambda)=<S34>/<S11>. The ratio R34(Theta,lambda) was shown previously
      to be sensitive to diameters of rod-shaped and spherical bacteria suspended in
      liquids. The present paper isolates the effect of length changes and shows that
      R34(Theta,lambda) is not very sensitive to these changes, but D(Theta,lambda) is
      sensitive to length changes when the aspect ratio becomes small enough. In the
      present article, we extend our analysis to vegetative bacteria which, because of
      their high percentage of water, generally have a substantially lower index of
      refraction than spores. The parameters used for the calculations were chosen to
      simulate values previously measured for log-phase Escherichia coli. Each
      individual E. coli bacterium appears microscopically approximately like a right
      circular cylinder, capped smoothly at each end by a hemisphere of the same
      diameter. With the present model we focus particular attention on determining the
      effect, if any, of length changes on the graphs of D(Theta,lambda) and
      R34(Theta,lambda). We study what happens to these two functions when the
      diameters of the bacteria remain constant and their basic shape remains that of a
      capped cylinder, but with total length changed by reducing the length of the
      cylindrical part of each cell. This approach also allows a test of the model,
      since the limiting case as the length of the cylindrical part approaches zero is
      exactly a sphere, which is known to give a value identically equal to zero for
      D(Theta,lambda) but not for R34(Theta,lambda).

PMID- 19844298
TI  - High power handling shape memory alloy optical fiber connector.
AB  - We present a novel shape memory alloy-based optical fiber splicing device that
      can provide robust, low loss, and high power handling splices between single-mode
      fibers of identical or entirely different glass compositions. The achieved splice
      loss was as low as 0.12 dB between two SMF-28 fibers with an average value of
      0.23 dB. To the best of our knowledge, this is the first demonstration of a
      purely mechanical splicing device that can withstand optical powers in excess of
      10 W with various combinations of silica and fluoride fibers. The device can be
      used in moderate to high power all-fiber components, especially those involving
      junctions unsuitable to fusion splicing, such as fiber lasers and amplifiers
      based on fluoride, chalcogenide, or microstructured fibers.

PMID- 19844300
TI  - Ultrabroadband midinfrared generation by using group-velocity-dispersion
      tailoring in a Bragg reflection waveguide for a difference-frequency-generation
      process.
AB  - We propose a novel scheme for ultrabroadband midinfrared (mid-IR) generation
      using quasi-phase-matched difference-frequency generation (DFG) in a
      GaN/Al(x)Ga(1-x)N based Bragg reflection waveguide (BRW). By optimally tailoring
      the phase- and group-velocity dispersion properties of symmetric BRWs, we show
      that the phase-matching condition for a DFG process could be maintained over a
      broad range of signal wavelengths. This could lead to generation of an
      approximately 700 nm broad idler close to 3.26 microm wavelength. Since the idea
      is based on dispersion compensation using photonic bandgap geometry, we can shift
      the broadband features to any desired spectral region and for any material system
      within the constraints imposed by the transparency of nonlinear materials. We
      also investigate the possibility of broadband mid-IR generation using pump
      sources with broad spectral width.

PMID- 19844299
TI  - Insect monitoring with fluorescence lidar techniques: feasibility study.
AB  - We investigate the possibilities of light detection and ranging (lidar)
      techniques to study migration of the damselfly species Calopteryx splendens and
      C. virgo. Laboratory and testing-range measurements at a distance of 60 m were
      performed using dried, mounted damselfly specimens. Laboratory measurements,
      including color photography in polarized light and spectroscopy of reflectance
      and induced fluorescence, reveal that damselflies exhibit reflectance and
      fluorescence properties that are closely tied to the generation of structural
      color. Lidar studies on C. splendens of both genders show that gender can be
      remotely determined, especially for specimens that were marked with Coumarin 102
      and Rhodamine 6G dyes. The results obtained in this study will be useful for
      future field experiments, and provide guidelines for studying damselflies in
      their natural habitat using lidar to survey the air above the river surface. The
      findings will be applicable for many other insect species and should, therefore,
      bring new insights into migration and movement patterns of insects in general.

PMID- 19844301
TI  - Propagation length of surface plasmons in a metal film with roughness.
AB  - The propagation of laser-excited surface plasmons along a gold film with surface
      roughness is directly observed via scattered light. The attenuation length of
      surface plasmons in a broad wavelength interval is calculated for smooth gold and
      silver films. The surface roughness, which was characterized with an AFM,
      introduces corrections to the attenuation length, angular dependence of the
      surface plasmon resonance, and the effective dielectric constant of the metal
      film. These corrections are also taken into account and discussed.

PMID- 19844302
TI  - Carrier-envelope phase stabilization and control of 1 kHz, 6 mJ, 30 fs laser
      pulses from a Ti:sapphire regenerative amplifier.
AB  - Carrier-envelope (CE) phase stabilization of a two-stage chirped pulse amplifier
      laser system with regenerative amplification as the preamplifier is demonstrated.
      The CE phase stability of this laser system is found to have a 90 mrad rms error
      averaged over 50 laser shots for a locking period of 4.5 h. The CE phase locking
      was confirmed unambiguously by experimental observation of the 2pi periodicity of
      the high-order harmonic spectrum generated by double optical gating.

PMID- 19844303
TI  - Mid-infrared ethene detection using difference frequency generation in a quasi
      phase-matched LiNbO3 waveguide.
AB  - A periodically poled LiNbO3 (PPLN) crystal waveguide has been used to produce up
      to 200 microW of mid-infrared light around 3081 cm(-1) with a wide tunability
      range of approximately 35 cm(-1). Two commercial near-infrared diode lasers at
      1.064 microm (pump) and 1.583 microm (signal) are mixed in a nonlinear optical
      crystal to achieve difference frequency generation. The 48 mm long directly
      bonded quasi-phase-matched (QPM) PPLN waveguide shows a conversion efficiency of
      12.3% W(-1). Applications in trace gas detection have been demonstrated for
      ethene, using multipass absorption coupled with wavelength modulation
      spectroscopy, and cavity enhanced absorption spectroscopy with a lock-in
      detection scheme: bandwidth reduced sensitivities of alpha(min)=8 x 10(-9) and
      1.6 x 10(-8) cm(-1) Hz(-1/2)(2sigma), respectively, have been achieved.

PMID- 19844304
TI  - Measurement of two dimensional refractive index profiles of channel waveguides
      using an interferometric technique.
AB  - Two dimensional refractive index profiles of ion exchanged channel waveguides in
      glass have been measured using an interferometric method. In order to obtain
      depth data, a shallow bevel is produced in the glass by polishing. A
      regularization algorithm for the extraction of the phase data from the
      interferometer image is presented. The method is applied to waveguides formed by
      the electric field assisted diffusion of Cu+ ions into a borosilicate glass. The
      index change obtained from the interferometer is in good agreement with that
      obtained from measurements on planar waveguides.

PMID- 19844305
TI  - Microreflectance difference spectrometer based on a charge coupled device camera:
      surface distribution of polishing-related linear defect density in GaAs (001).
AB  - We describe a microreflectance difference (microRD) spectrometer based on a
      charge coupled device (CCD), in contrast to most common RD spectrometers that are
      based on a photomultiplier or a photodiode as a light detector. The advantage of
      our instrument over others is the possibility to isolate the RD spectrum of
      specific areas of the sample; thus topographic maps of the surface can be
      obtained. In our setup we have a maximum spatial resolution of approximately 2.50
      microm x 2.50 microm and a spectral range from 1.2 to 5.5 eV. To illustrate the
      performance of the spectrometer, we have measured strains in mechanically
      polished GaAs (001) single crystals.

PMID- 19844306
TI  - Optical near-field study of photonic crystal tapers.
AB  - A scanning near-field optical microscopy study is undertaken on photonic crystal
      tapers. These tapers are used to couple a 3 microm wide multimode dielectric
      waveguide to a single-line defect monomode photonic crystal waveguide. Two kinds
      of taper, with or without a localized defect, are compared. Higher transmission
      efficiency is obtained when a defect is utilized. The near-field study at 1550 nm
      shows experimentally that this defect prevents leaky resonant states to appear in
      the taper and thus permits a decrease in out-of-plane losses. These observations
      are supported by band diagram calculations.

PMID- 19844307
TI  - Continuous self-imaging regime with a double-grating mask.
AB  - We analyze the Talbot effect produced by a mask composed of two diffraction
      gratings. Combinations with phase and amplitude gratings have been studied in the
      near-field regime. For a two-phase-gratings configuration, the Talbot effect is
      canceled, even when using monochromatic light; that is, the intensity
      distribution is nearly independent of the distance from the mask to the
      observation plane. Therefore, the mechanical tolerances of devices that use the
      Talbot effect may be improved. In addition, the spatial frequency of the fringes
      is quadrupled, which improves the accuracy of devices that employ this mask. An
      experimental verification for the best case two phase gratings, has also been
      performed, validating the theoretical results.

PMID- 19844309
TI  - Liquid tunable double-focus lens fabricated with diamond cutting and soft
      lithography.
AB  - With the use of diamond cutting processes, namely turning and shaping, followed
      by soft lithography with polydimethylsiloxane, a liquid tunable double-focusing
      lens is fabricated. Data from a mechanical profiler verified that the dimensions
      of the features of the lens device adhere well to designed values. In addition,
      atomic force microscopy results show that this method of fabrication is able to
      produce multiple replicas of the lens device with a high-quality surface finish
      that is suitable for optical purposes. Lastly, the tunability of the lens is
      demonstrated, with experimental results agreeing well with simulation results.

PMID- 19844308
TI  - Effects of residue and antioxidant on thermo-optical properties of biodiesel.
AB  - Thermal lens (TL) spectrometry was applied to soybean biodiesel samples, in order
      to assess the behavior of their thermo-optical properties during the preparation
      before and after the washing process. The study was based on the thermal
      diffusivity parameter, which is highly sensitive and is related to the chemical
      composition of the sample. The results showed a difference of approximately 20%
      between the initial (unwashed) and the final (washed) steps of biodiesel
      production. This behavior indicates that the residue of the biodiesel production
      influences the thermal diffusivity value. Consequently, TL spectrometry can be a
      useful methodology for certifying the quality of biodiesel during production.

PMID- 19844310
TI  - Visual performance after LASIK for a Q-optimized and a standard ablation
      algorithm.
AB  - We test visual performance after LASIK (laser in situ keratomileusis) for a Q
      optimized ablation algorithm and one based on the Munnerlyn formula. The visual
      functions tested include aberrometry, monocular and binocular contrast
      sensitivity function (CSF), and a discrimination test under low-illumination
      conditions. This test is useful to quantify night-vision disturbances. A total of
      102 patients took part in the experiments, and visual data were taken before
      (with best correction) and after LASIK. Results show a deterioration in
      aberrometry, CSF, binocular summation, and discrimination index for the two
      algorithms tested, although this deterioration is significantly lower for the Q
      optimized algorithm.

PMID- 19844311
TI  - Using integrating spheres as absorption cells: path-length distribution and
      application of Beer's law.
AB  - We have modeled the path-length distribution in an integrating sphere used as a
      multipass optical cell for absorption measurements. The measured radiant flux as
      a function of analyte concentration is nonlinear as a result, deviating from that
      expected for a single path length. We have developed a full numerical model and
      introduce a new analytical relationship that describes this behavior for high
      reflectivity spheres. We have tested both models by measuring the optical
      absorption of methane at 1651 nm in a 50 mm diameter sphere, with good agreement
      with experimental data in the absorption range of 0-0.01 cm(-1). Our results
      compare well with previous work on the temporal response of integrating spheres.

PMID- 19844312
TI  - Study on optical constants of ITO:Ag nanocompsite films.
AB  - Indium tin oxide (ITO) thin films doped with a volume ratio of 0.3% Ag were
      prepared by sputtering and subsequently annealed in temperatures of 200, 260,
      300, 360, and 400 degrees C. The annealed films show increased transmittance in
      the visible wavelength range. The refractive index n and extinction coefficient k
      were extracted from simulating the transmittance spectra by using spectroscopic
      ellipsometry analysis method. The n values apparently increased in the whole
      wavelength range, but the k values were found to have almost no change in the
      near ultraviolet region after Ag doping. It is, therefore, proposed that the
      ITO:Ag combined with an ITO multilayer structure can be applied in special
      optical devices.

PMID- 19844313
TI  - Design and experimental validation of a snapshot polarization contrast imager.
AB  - We present a degree of polarization imaging system based on a Wollaston prism and
      a single CCD camera. This architecture eliminates technical inaccuracies and
      noise sources that are present in experimental setups containing a polarization
      switching element. After the acquisition of two images corresponding to two
      orthogonal states of polarization, one can compute the orthogonal state contrast
      image (OSCI), which is an estimate of the local degree of polarization of the
      backscattered light when the observed materials are purely depolarizing. The
      instrument design coupled to an efficient calibration enables the estimation of
      the OSCI from a single image acquisition and significant reduction of technical
      noise present in other polarization imaging systems. The setup was tested in
      realistic conditions where it represents a real asset.

PMID- 19844314
TI  - Polarimetric stellar interferometry by use of birefringent retarders.
AB  - We propose a polarimetric technique for a stellar interferometer that uses two
      birefringent retarders inserted into each arm of the interferometer. The
      retarders shift the interference fringes of the two orthogonal polarizations to
      opposite directions along an optical path difference (OPD), which enables us to
      measure the polarized fringe visibilities separately. Laboratory demonstrations
      were carried out using quartz retarders with a thickness of 1.124 mm, and the
      separation of the interferometric fringes of +/-10 microm along the OPD was
      observed. We discuss a calibration method for the acquired fringes to obtain
      reliable estimations of polarized fringe visibilities. We also discuss
      feasibility of the proposed technique for the Mitaka optical InfraRed Array (MIRA
      I.2).

PMID- 19844315
TI  - Holographic projection based on diamond-turned diffractive optical elements.
AB  - We introduce an approach to generate holographic data for diffractive optical
      elements fabricated by means of a diamond-turning process. The aim is to project
      a predefined intensity distribution in the far-field domain of the corresponding
      diffractive surface. The method takes into consideration typical constraints that
      result from the fabrication process, such as the spiral path of the turning tool
      and the fact that only the phase distribution of the incident light can be
      manipulated.

PMID- 19844316
TI  - Cross-correlation technique for dispersion characterization of chirped volume
      Bragg gratings.
AB  - We propose using cross-correlation frequency-resolved optical gating for
      dispersion characterization of optical elements with high dispersion, such as
      ultrashort pulse stretchers and compressors. The technique is based on spectrally
      resolved second-order cross correlation (sum frequency generation) of a stretched
      pulse with a reference short pulse. Dispersion of optical elements with a high
      pulse stretching ratio can be completely characterized using this method, even
      with moderate resolution of spectral measurements of the cross-correlation
      signal. The proposed technique is used to measure dispersion of a chirped Bragg
      grating recorded in photo-thermo-refractive glass. It was found that dispersion
      of these gratings is almost linear with wavelength and has approximately the same
      slope with opposite signs for two orientations of the grating with opposite faces
      of the grating used as the input face. Analysis of higher-order dispersion of the
      grating shows some variations of dispersion across the aperture of the grating,
      mostly in the amount of third-order dispersion contribution.

PMID- 19844317
TI  - Photometric model of diffuse surfaces described as a distribution of interfaced
      Lambertian facets.
AB  - The Lambertian model for diffuse reflection is widely used for the sake of its
      simplicity. Nevertheless, this model is known to be inaccurate in describing a
      lot of real-world objects, including those that present a matte surface. To
      overcome this difficulty, we propose a photometric model where the surfaces are
      described as a distribution of facets where each facet consists of a flat
      interface on a Lambertian background. Compared to the Lambertian model, it
      includes two additional physical parameters: an interface roughness parameter and
      the ratio between the refractive indices of the background binder and of the
      upper medium. The Torrance-Sparrow model--distribution of strictly specular
      facets--and the Oren-Nayar model--distribution of strictly Lambertian facets-
      appear as special cases.

PMID- 19844318
TI  - Terminal reflections in fiber-optic image guides.
AB  - Fibered image guides for confocal reflectance endomicroscopy suffer from Fresnel
      reflections at the fiber terminals, which can limit signal-to-noise ratio in
      these systems. A model that describes these terminal reflections is presented to
      better understand how they can be managed most effectively. An expression for the
      refractive index of termination that minimizes the reflection as a function of
      the fiber's normalized frequency is derived for step-index fibers, while a
      graphical solution is presented for graded-index fibers. The model predicts that
      terminal reflections from graded-index fibers are more sensitive to variations in
      fiber size and changes in wavelength than step-index fibers. A method is also
      presented to measure the refractive index that allows one to minimize the
      terminal reflections in an image guide. The technique uses the inherent mode
      coupling of the fibers in the image guide, allowing the isolation and measurement
      of reflections from only one end of the fiber. An achievable minimum
      backreflection of -36 dB was measured at 635 nm in a commercial image guide with
      30,000 fibers.

PMID- 19844319
TI  - Ice crystal habits from cloud chamber studies obtained by in-line holographic
      microscopy related to depolarization measurements.
AB  - We investigate hydrometeor habits at the AIDA chamber with a newly developed in
      line holographic microscope HOLographic Imager for Microscopic Objects (HOLIMO).
      Sizes and habits of ice crystals and droplets in a mixed-phase cloud experiment
      are related to relative humidity with respect to ice (RH(ice)), temperature (T),
      and experiment time. This experiment is initiated with supercooled water drops.
      As a result, ice crystals within a maximum particle diameter size range of 2 to
      118 microm (average size of 19 microm) are detected and 63% of them reveal
      regular habits. The observed particle habits match those predicted for a given
      RH(ice) and T. Two different growth modes emerge from this cloud. The first one
      appears during water injection and reveals mainly optical particle sizes in the
      range of 5 to 250 microm. The second mode grows to sizes of 5 to 63 microm, just
      after the particles of the first one fall out. It is found that an increasing
      aspect ratio chi of maximum length over thickness from 2 to 20 as obtained by
      HOLIMO corresponds to a decreasing linear depolarization ratio from 0.1 to 0.04,
      as independently obtained by depolarization measurements.

PMID- 19844320
TI  - Distributed fiber sensor based on modulated pulse base reflection and Brillouin
      gain spectrum analysis.
AB  - In recent years, several distributed sensor systems based on stimulated Brillouin
      scattering in optical fibers have been proposed [J. Intell. Mater. Syst.
      Struct.10, 340 (1999); Proc. SPIE5855, 555 (2005)]. We propose a simpler scheme
      based on fiber-end reflection and Brillouin gain spectrum analysis. In this
      setup, only one optical source is necessary to provide both the pump and the
      probe wave; the latter is provided by the modulated pulse base. First, the
      physical mechanisms for two different Brillouin scattering processes in our
      sensor system are analyzed and an approximate theory model is proposed. In
      addition, it is demonstrated that the simple system configuration allows
      simultaneous acquisition of the time-domain and the frequency-domain information.
      It is experimentally demonstrated that this configuration is effective for strain
      measurements and could as well be applied to temperature monitoring.

PMID- 19844321
TI  - Measurement of Faraday rotation using phase-sensitive low-coherence
      interferometry.
AB  - We report a differential phase sensor capable of measuring Faraday rotation in
      reflection mode with a single measurement and a small field-depth factor. Based
      on a polarization-maintaining-fiber low-coherence interferometer, the sensor
      measures phase difference between two decorrelated and oppositely polarized
      circular states incident on a sample. Sensitivity of the sensor for the Faraday
      rotation is 0.31 arcmin, allowing applications on small volumes of liquids. The
      Verdet constants of various liquids, including clear and turbid samples, are
      measured at 857 nm.

PMID- 19844322
TI  - Elimination of a zero-order beam induced by a pixelated spatial light modulator
      for holographic projection.
AB  - A technique is proposed theoretically and verified experimentally to eliminate a
      zero-order beam caused by a pixelated phase-only spatial light modulator (SLM)
      for holographic projection. The formulas for determination of the optical field
      in the Fourier plane are deduced, and the influence of the pixelated structure of
      a SLM on the intensity of the zero-order beam is numerically investigated. Two
      currently existing techniques are studied and a new one is presented. These three
      techniques are used separately to eliminate the zero-order interruption, and the
      optical performances of the reconstructed patterns are compared. The new
      technique results in higher reconstruction quality and diffraction efficiency. A
      short animated movie is illuminated for holographic projection display. The
      experimental results show that the zero-order beam can be efficiently eliminated
      by the new technique. It is believed that this technique can be used in various
      optical systems that are based on pixelated phase-only SLMs, such as holographic
      optical tweezers and optical testing systems.

PMID- 19844323
TI  - Whispering-gallery mode excitation in a microdroplet illuminated by a train of
      chirped ultrashort laser pulses.
AB  - The peculiarities of resonant optical field excitation inside a water
      microdroplet under illumination by a spatially bounded Gaussian beam with a
      temporal regime of a single chirped ultrashort laser pulse and a chirped pulse
      train are considered. It is established that the coupling efficiency of incident
      radiation to a selected high-Q whispering-gallery mode significantly depends on
      the interpulse interval in the train and chirping parameter of pumped laser
      radiation. The influence of the geometry of particle illumination by a laser beam
      and of the number of pulses in the train on the whispering-gallery mode buildup
      and its peak intensity is investigated.

PMID- 19844324
TI  - Reducing the effect of integrating sphere speckle when characterizing the
      instrument line shape of a Fourier-transform hyperspectral imager.
AB  - The contribution of integrating sphere speckle pattern on the instrument line
      shape of a Fourier-transform hyperspectral imager is investigated. A new
      measurement technique that minimizes the speckle effect is presented. This
      technique consists of agitating the sphere while integrating with the instrument
      camera. Experimental results are presented that show the speckle effect on the
      instrument line shape and how it can be removed. This work is motivated by the
      constant goal of better identification and correction of the instrument line
      shape.

PMID- 19844325
TI  - Windowed defocused photographic speckle vibration measurement.
AB  - The out-of-plane vibration of a rough surface causes an in-plane vibration of its
      speckle pattern when observed with a defocused optical photographic system. If
      the frequency of the oscillations is high enough, a time-averaged specklegram is
      recorded from which the amplitude of the vibration can be estimated. The
      statistical character of speckle distributions along with the pixel sampling and
      intensity analog-to-digital conversion inherent to electronic cameras degrade the
      accuracy of the amplitude measurement to an extent that is analyzed and
      experimentally tested in this paper. The relations limiting the mutually
      competing metrological features of a defocused speckle system are also deduced
      mathematically.

PMID- 19844326
TI  - Anomalous reflection in a metallic plate with subwavelength grooves of circular
      cross section.
AB  - Resonant features in the response of finite arrays of rectangular grooves ruled
      on a metallic plate have been reported in connection with the excitation of phase
      resonances. These anomalies are generated by a particular arrangement of the
      magnetic field phases inside the subwavelength grooves when the structure is
      illuminated by a p-polarized electromagnetic wave. We show that this kind of
      resonance is also present for grooves of circular cross section and appear as
      sharp peaks in the specular response, the number of which increases with the
      number of grooves in the structure. A significant intensification of the field
      within the grooves is also found for these particular phase configurations. The
      dependence of the response on the geometrical parameters of the structure is
      analyzed in detail, in order to consider these structures for potential
      applications such as frequency selectors and polarizers.

PMID- 19844327
TI  - Minimum-variance Brownian motion control of an optically trapped probe.
AB  - This paper presents a theoretical and experimental investigation of the Brownian
      motion control of an optically trapped probe. The Langevin equation is employed
      to describe the motion of the probe experiencing random thermal force and optical
      trapping force. Since active feedback control is applied to suppress the probe's
      Brownian motion, actuator dynamics and measurement delay are included in the
      equation. The equation of motion is simplified to a first-order linear
      differential equation and transformed to a discrete model for the purpose of
      controller design and data analysis. The derived model is experimentally verified
      by comparing the model prediction to the measured response of a 1.87 microm
      trapped probe subject to proportional control. It is then employed to design the
      optimal controller that minimizes the variance of the probe's Brownian motion.
      Theoretical analysis is derived to evaluate the control performance of a specific
      optical trap. Both experiment and simulation are used to validate the design as
      well as theoretical analysis, and to illustrate the performance envelope of the
      active control. Moreover, adaptive minimum variance control is implemented to
      maintain the optimal performance in the case in which the system is time varying
      when operating the actively controlled optical trap in a complex environment.

PMID- 19844328
TI  - Axial imaging necessitates loss of lateral shift invariance: proof with the
      Wigner analysis.
AB  - We present a proof of the conjecture reported in Stein and Barbastathis ["Axial
      imaging necessitates loss of lateral shift invariance," Appl. Opt.41, 6055-6061
      (2002)] that axial imaging necessitates loss of lateral shift invariance. We
      apply the Wigner distribution function (WDF) to the axial imaging process and
      compare laterally shift variant and invariant imaging systems. Two conditions for
      axial imaging are established: (i) objects with spatially variant local spatial
      frequency content to create sufficient change in the WDF with defocus and (ii)
      properly designed shift variant imaging kernels to estimate the slope of the
      sheared WDF. The lateral shift variance is a necessary condition for axial
      imaging. We use two examples from Stein and Barbastathis to show how axial
      imaging is interpreted in Wigner space.

PMID- 19844329
TI  - Free-space azimuthal paraxial wave equation: the azimuthal Bessel-Gauss beam
      solution.
AB  - We develop a paraxial wave equation for an azimuthally polarized field
      propagating in free space. The equation's beamlike solution is composed of a
      plane-wave propagation factor multiplied by a Bessel function of the first kind,
      of order one, and a Gaussian factor, which describe the transverse
      characteristics of the beam. We compare the propagation characteristics of the
      azimuthal Bessel-Gauss beam solution with a solution of the more familiar scalar
      paraxial wave equation, the linearly polarized Bessel-Gauss beam.

PMID- 19844330
TI  - Dielectric polarizability of a sphere with arbitrary anisotropy.
AB  - The polarizability of a dielectrically anisotropic sphere is studied. The
      anisotropy is general, consisting of a symmetric and an antisymmetric part of the
      permittivity dyadic. The polarizability is also dyadic, with its components
      depending on the relations of the permittivity components of the material. In
      certain special cases the components of the polarizability matrix decouple and
      become functions only of the corresponding permittivity components, but in
      general all nine polarizabilities depend on all nine permittivities.

PMID- 19844331
TI  - Selective mode excitation in graded-index multimode fiber by a computer-generated
      optical mask.
AB  - We report on the generation of optical masks that permit the spatial shaping of a
      laser beam so that one can selectively excite single modes of a multimode
      parabolic graded-index optical fiber. The amplitude masks are determined by the
      analytical radial function of the fiber mode in the weakly guiding approximation.
      Phase reversal is encoded on the transparency through a shifted-grating
      technique. Effective injection and propagation of a single mode in a largely
      multimode fiber are shown as examples.

PMID- 19844332
TI  - Propagation of TM modes in a nonlinear liquid-crystal waveguide.
AB  - A cpylindrical nematic liquid-crystal waveguide with an infinite homogeneous
      isotropic cladding is considered. The dielectric tensor of the liquid-crystal
      core that governs wave propagation is determined by the configuration of the
      nematic director. Propagating optical fields can alter the director configuration
      and thus change the dielectric tensor. We use an iterative numerical scheme to
      determine the propagation constant as a function of optical power.

PMID- 19844333
TI  - Photoinduced second-harmonic generation in fibers doped with rare-earth ions.
AB  - Photoinduced second-harmonic generation in silica fibers doped with Er(3+),
      Sm(3+), and Tb(3+) has been investigated. Er(3+)-doped fibers have been found to
      tune a chi((2)) grating easily to the mode structure of the laser radiation,
      whereas Sm(3+)-doped fibers have been found to possess the greatest resistance to
      chi((2)) grating erasure by radiation at 532 nm. From the beginning of the
      preparation processes, the third harmonic at 355 nm is registered in all the
      fibers.

PMID- 19844334
TI  - Multikilohertz stimulated Brillouin scattering.
AB  - We report, for the first time to our knowledge, multikilohertz stimulated
      Brillouin-scattering phase conjugation of copper-vapor laser radiation. The small
      wavelength shift associated with the Stokes radiation is shown to permit double
      pass aberration correction of the copper-vapor laser, avoiding the postlasing
      absorption. Preliminary results on the effects of stimulated-Brillouin-scattering
      medium type, purity, geometry, and flow on the efficiency are presented, as is an
      initial assessment of the conjugation fidelity.

PMID- 19844335
TI  - Bright-bright 2pi solitons in stimulated Raman scattering.
AB  - We found conditions for excitation of bright-bright 2pi solitons in stimulated
      Raman scattering that involves nutation of population at Raman quantum levels,
      for two (laser-Stokes) and three (e.g., laser-Stokes-anti-Stokes) components. The
      soliton components at all participating frequencies are bright solitons of the
      same, Lorentzian, shape, in contrast to the well-known bright-dark soliton
      combination in stimulated Raman scattering.

PMID- 19844336
TI  - Experimental control of chaos in a laser-diode interferometer with delayed
      feedback.
AB  - Chaos has been controlled with the occasional proportional feedback technique in
      a delayed optical bistable system that consists of a laser-diode interferometer
      with a delayed optoelectronic feedback. A variety of subharmonic periodic orbits
      and high mode oscillations are stabilized at different time delays. No knowledge
      about the dynamical equation is required for the control. The synchronizing
      frequency can be readily estimated from the ratio of the delay and the system
      relaxation times.

PMID- 19844337
TI  - Transient self-diffraction in Nd:YAG saturable amplifiers.
AB  - We investigate self-diffraction and multiwave scattering by a nonsinusoidal gain
      grating induced in a thick laser medium with pulses of duration much less than
      the population relaxation time. The energies of the transmitted and of the two
      first-order self-diffracted beams are calculated. Experimental measurements
      performed in a flash-lamp-pumped Nd:YAG amplifier at lambda = 1.064 microm show
      good agreement with the theoretical results. A total energy in the two first
      order scattered waves of 1.1 mJ is obtained for a total incident energy of 14 mJ.

PMID- 19844338
TI  - Selective launching of higher-order modes into an optical fiber with an optical
      phase shifter.
AB  - We demonstrate a simple, effective technique for launching higher-order modes
      into a double-mode optical fiber by using an optical phase shifter at the input
      end. The suppression of the lowest-order mode was measured (but not limited) to
      be 27 dB.

PMID- 19844339
TI  - Optimal design of single-cladded dispersion-compensating optical fibers.
AB  - Specific and simple design relations are presented for different classes of
      single-cladded optical fibers designed to obtain maximum dispersion compensation.
      The performance limitations of the different fibers are compared, and the needs
      for very high refractive-index differences are evaluated.

PMID- 19844340
TI  - Photoinduced birefringence rotation in germanosilicate glass optical fiber.
AB  - Experimental results are reported for the permanent photoinduced rotation of the
      principal axes of the birefringence in a circular-core single-mode optical fiber
      on exposure of the fiber to powerful argon-laser radiation at 488 nm. The
      linearly polarized laser beam was launched into the fiber along one of the
      principal axes of the initial birefringence in the fiber. After several exposures
      totaling 4 h, a rotation of as much as 57 degrees was observed in the
      orientations of the principal axes in addition to the photoinduced birefringence.

PMID- 19844341
TI  - Wavelength dependence of two-photon absorption properties of silica optical
      fibers.
AB  - Two-photon absorption coefficients in ultraviolet-grade optical fibers are
      measured in the range of 219-260 nm. A frequency-doubled tunable dye laser is
      used as the light source. The two-photon absorption coefficient increases
      exponentially with an increase in the photon energy. The exciton peak does not
      appear in the spectrum. Theoretical values are calculated by the Keldysh formula
      and compared with the experimental results.

PMID- 19844342
TI  - Electro-optic phase modulation in a silica channel waveguide.
AB  - We report what is to our knowledge the first demonstration of electro-optic phase
      modulation in a fused-silica channel waveguide. The nonlinearity is induced
      through elevated temperature poling of an electron-beamirradiated waveguide. A
      phase shift of 32 mrad was measured at lambda = 633 nm for a device interaction
      length of 4.8 mm and an applied electric field of 7.3 V/microm.

PMID- 19844343
TI  - Thin-film grating polarizer.
AB  - The deexcitation of guided modes in a thin-film planar dielectric waveguide is
      considered. On the film-cover interface is etched an ordinary diffraction grating
      whose wave number is such that one radiation beam in the substrate alone is
      generated. For a specified radiation direction the p-polarized radiation vanishes
      selectively. This phenomenon is used in the development of a polarizer whose
      output is predominantly in the p polarization. The sensitivity of the performance
      of the polarizer to small deviations in the design parameters is also
      investigated.

PMID- 19844344
TI  - Simple rate-equation model for two-photon lasers.
AB  - We present a rate-equation model for two-photon lasers that, despite its
      simplicity, captures the essential physics of their behavior and affords an
      intuitive understanding of their novel threshold and stability behavior. We use
      the model to investigate the steady-state behavior of the laser, explore the
      stability of the steady-state solutions, and predict the injected pulse strength
      needed to initiate lasing.

PMID- 19844345
TI  - 1.9-W cw ring-cavity KTP singly resonant optical parametric oscillator.
AB  - We report high-power and single-frequency operation of a continuous-wave singly
      resonant potassium titanyl phosphate (KTiOPO(4)) optical parametric oscillator in
      a ring-cavity configuration. The ring singly resonant optical parametric
      oscillator threshold is 4.3 W. When the oscillator is pumped by 6.7 W of 532-nm
      radiation from an 11.2-W single-frequency resonantly doubled Nd:YAG laser, 1.9 W
      of single-axial-mode output is generated at the idler wavelength of 1039 nm.

PMID- 19844346
TI  - Photocurrents in photoconductive semiconductors generated by a moving space
      charge field.
AB  - The behavior of photocurrents generated in the semiconductors InP:Fe, GaAs:Cr,
      and undoped GaAs inoptical two-wave mixing experiments as a function of the
      frequency difference between the two waves is characterized and verified
      experimentally. The sign, the concentration, and the ratio gammaR/micro of the
      dominant charge carriers and the effective concentration of trapping centers can
      be found from this dependence.

PMID- 19844347
TI  - Nearly quantum-limited timing jitter in a self-mode-locked Ti:sapphire laser.
AB  - The experimentally measured timing jitter of a self-mode-locked Ti:sapphire laser
      is compared with the theoretically predicted quantum limit. Timing jitter figures
      of 150 fs (100-500 Hz) and 80 fs (500-5000 Hz), which approach the quantum limit,
      have been achieved by use of an improved cavity phase-locking technique.

PMID- 19844348
TI  - X rays from microstructured targets heated by femtosecond lasers.
AB  - We have demonstrated efficient conversion of ultrashort-pulse laser energy to x
      rays with energies above 1 keV, using laser-produced plasmas generated on a
      variety of microstructured surfaces. Lithographically produced grating targets
      generated 0.1 mJ of kilo-electron-volt x rays, and porous gold and aluminum
      targets emitted 1 mJ. This represents an improvement of a factor of 100 over flat
      targets. The K-shell emission spectrum of porous aluminum was composed primarily
      of heliumlike spectral lines.

PMID- 19844349
TI  - Interferometric measurement of wavelength dispersion on femtosecond laser
      cavities.
AB  - Cavity Fourier-transformed cross correlation measures the wavelength dispersion
      from the cross-correlation signal taken on spontaneous emission emerging from a
      cavity under test. This method provides a universal and quick way to detect
      femtosecond group delay. However, test cavity-length fluctuations have been
      hindering its application to femtosecond laser cavities. We introduce a dual
      interferometer scheme in which one of the interferometers is dedicated to
      detecting length change in the test cavity, thereby enabling the influence of
      fluctuations to be nullified. This method is demonstrated on a Ti:Al(2)O(3) laser
      as well as on a NaCl color-center laser.

PMID- 19844350
TI  - Passive stabilization of a synchronously mode-locked NaCl color-center laser by
      coherent photon seeding.
AB  - We use coherent photon seeding to passively stabilize a synchronously mode-locked
      NaCl color-center laser. This results in the generation of essentially transform
      limited picosecond pulses with average power levels of as high as 1.3 W in the
      1.5-1.7-microm range. In addition, the pulse energy fluctuations are reduced by
      as much as 1 order of magnitude.

PMID- 19844351
TI  - Nonisoplanatic imaging by phase diversity.
AB  - Phase diversity allows one to use multiple images with known phase changes such
      as defocus to learn the optical characteristics of an imaging medium and to
      estimate the unknown object. It is shown that the method can be extended to the
      case in which the optical system is nonisoplanatic; thus it can recover both the
      extended object and the angle-dependent, aberrating phase of the medium. The
      technique is a timely extension of the conventional phase-diversity concept and
      could be used to solve the isoplanatic patch problem of adaptive optics, to
      determine a spatially varying point-spread function in image restoration, and to
      image through a single-fiber optic.

PMID- 19844352
TI  - Random mask encoding of multiplexed phase-only and binary phase-only filters.
AB  - In the formation of multiplexed filters, the phase-only and binary phase-only
      operations result in spurious cross terms and a nonlinear scaling. We use
      complementary random binary patterns having different pattern densities to encode
      the various functions within the multiplexed function. The orthogonality of these
      complementary masks permits separability of the phase-only or binary phase-only
      operations. By changing the pixel density of the random pattern, we can easily
      change the relative weights of the functions that compose the multiplexed filter.
      Experimental results are shown that demonstrate the effectiveness of this
      approach.

PMID- 19844353
TI  - VUV and UV fluorescence and absorption studies of Pr(3+)-doped LiLuF(4) single
      crystals.
AB  - The laser-induced fluorescence spectrum of LiLuF(4):Pr(3+) single crystals,
      pumped by an F(2) pulsed-discharge molecular laser at 157 nm, was obtained in the
      VUV and UV regions of the spectrum at room temperature. A number of new
      fluorescence peaks were observed for the first time to our knowledge. They were
      assigned to the dipole-allowed transitions 4f5d ? 4f(2) of Pr(3+) ion. In
      addition, the absorption spectrum of the crystal samples was recorded. The
      positions of the bands with the 4f5d configuration were found to be 46 412, 53
      267, and 63 397 cm(-1) from the ground state, (3)H(4), of the Pr(3+) ion. The
      edge (onset) of the 4f5d bands was at 45 100 cm(-1).

PMID- 19844354
TI  - Information capacity of holograms in photorefractive crystals.
AB  - From a single measurement of the signal-to-noise ratio of the image reconstructed
      from a hologram it is possible to estimate the information capacity of
      superimposed holograms and to predict the total number of superimposed holograms
      associated with the maximum information capacity. Information capacity densities
      of 3.7 x 10(6) bits/mm(3) for Bi(12)TiO(20) crystal samples and 2.3 x 10(8)
      bits/mm(3) for LiNbO(3) samples have been calculated.

PMID- 19844355
TI  - Method for direct measurement of the variance of laser beams.
AB  - A method permitting direct measurement of the spatial variance along a given
      transverse direction of any laser beam is described. The procedure relies on the
      use of a transmission filter whose local transmissivity varies spatially as an
      inverted parabola. The variance and the first moment of a transverse beam
      intensity distribution are readily obtained simply by measurement of the maximum
      power transmitted through the filter as this filter is moved across the beam's
      section.

PMID- 19844356
TI  - Normalized expressions for the optical sensitivity of evanescent wave sensors.
AB  - Normalized analytical expressions are derived for the maximum value of the modal
      field width, of the squared field amplitude at the superstrate boundary, and of
      the total power propagating in the superstrate in the case of the TE modes of a
      step-index slab waveguide.

PMID- 19844357
TI  - Minimum-complexity free-space optical nonblocking networks for multicast
      interconnect applications.
AB  - It was believed that, for strictly nonblocking multicast and broadcast
      interconnect operations to be achieved, a switching network had to have a minimum
      of N(2) switching states, i.e., a crossbar-type switch. A novel system concept
      that reduces the switching complexity while maintaining nonblocking multicast
      networking is proposed and experimentally demonstrated.

PMID- 19844358
TI  - Collapse of a transverse-mode continuum in a self-imaging photorefractively
      pumped ring resonator.
AB  - We demonstrate the collapse of a continuum of transverse modes in a self-imaging
      ring resonator that is photorefractively pumped. The resulting localized mode has
      an arbitrary transverse location. The mode collapse results from placing
      saturable photorefractive gain and loss media in spatially conjugate resonator
      planes. The transverse position of the localized mode is unstable under small
      cavity misalignments, and it drifts across the transverse aperture while
      retaining its spatial form.

PMID- 19844359
TI  - Image resolution by use of multiply scattered light.
AB  - We present calculations based on the Markov-chain technique of the intensity and
      direction of light traversing a multiply scattering medium in the isotropic
      scattering case for pulsed point-source illumination. From these calculations we
      derive expressions for the trade-off between spatial image resolution and
      detector integration time when the diffusion approximation is not valid. We show
      that image resolution better than the diffusion limit is theoretically possible
      use of multiply scattered light for samples thinner than ~35 scattering lengths.
      Monte Carlo simulations are used to extend these results to the anisotropic
      scattering case.

PMID- 19844360
TI  - Spatial solitons of Maxwell's equations.
AB  - Spatial solitons of Maxwell's equations propagating in an isotropic Kerr material
      differ significantly from the classical soliton of the nonlinear Schrodinger
      equation unless the electric field is linearly polarized along a geometric axis
      of the soliton intensity pattern. In general the polarization state changes
      continuously as the beam propagates, with a period of millimeters for highly
      nonlinear materials. This effect is due to the form birefringence of the soliton
      induced waveguide. Equivalently, a soliton of Maxwell's equations is composed of
      both the TE and TM modes of the axially uniform waveguide it induces. Modal
      beating leads to the polarization dynamics.

PMID- 19844361
TI  - Picosecond measurements of absorptive and refractive optical nonlinearities in
      GaP at 532 nm.
AB  - Picosecond time-resolved pump-probe and Z-scan measurements are used to
      investigate the nonlinear refraction and absorption associated with intense
      picosecond excitation above the indirect band edge of GaP. The pump-probe results
      reveal both an instantaneous absorption feature, which is consistent with two
      photon absorption, and a long-lived feature that is associated with the
      generation of free carriers by linear indirect absorption. Z scans conducted with
      pulses of 25- and 95-ps duration indicate that, for these pulse widths, the
      nonlinear refraction in GaP is dominated by the linear generation of free
      carriers and that the role of the electronic Kerr effect is negligible. The
      measured free-carrier refraction is compared with the value predicted from a
      simple model based on band filling. This model predicts that the primary
      contribution to the index change at the applied optical frequency arises from
      holes blocking direct transitions near the zone center and that similar blocking
      of indirect transitions has a negligible effect on the index.

PMID- 19844362
TI  - Observation of optical limiting and backscattering of nanosecond laser pulses in
      liquid-crystal fibers.
AB  - We report the recent observation of nonlinear-optical phenomena occurring in
      isotropic liquid-crystal-cored optical fibers, including passive all-optical self
      limiting effects, stimulated backscattering, and phase conjugation. These
      processes occur at relatively low thresholds and short fiber lengths.

PMID- 19844363
TI  - Dynamic independence of pulsed antiphased modes.
AB  - We analyze theoretically a case of antiphase dynamics in the self-pulsing regime
      involving two orthogonal polarizations in intracavity second-harmonic generation.
      We show that, for this model, antiphase dynamics may lead to a nonreciprocal
      independence of the two polarizations as a result of partial overlap between the
      pulses. In the case in which two modes oscillate with one polarization and a
      single mode oscillates with orthogonal polarization, we find that the two modes
      can display chaos while the orthogonal mode remains periodic, despite coupling
      among all the modes.

PMID- 19844364
TI  - Spectroscopic and photorefractive properties of infrared-sensitive rhodium-doped
      barium titanate.
AB  - We have grown and characterized crystals of BaTiO(3) doped with Rh. These
      crystals have a blue-green color that is probably due to charge-transfer optical
      transitions involving Rh(4+) and/or Rh(3+). Electron paramagnetic resonance
      spectroscopy confirmed the presence of Rh(4+) centers. Self-pumped phase
      conjugation measurements were performed at wavelengths between 776 and 990 nm.
      Reflectivities near 80% were obtained throughout this wavelength range. In
      addition, self-pumped phase-conjugation buildup times were measured as a function
      of input power at 851 nm and are significantly faster than in undoped or Co-doped
      crystals studied previously. BaTiO(3):Rh is therefore a promising material for
      near-infrared photorefractive applications.

PMID- 19844365
TI  - Comblike dispersion-profiled fiber for soliton pulse train generation.
AB  - A novel optical fiber [comblike dispersion-profiled fiber (CDPF)] that consists
      of a chain of alternating segments of standard telecommunication fiber and
      dispersion-shifted fiber is proposed for the generation of a soliton pulse train
      based on nonlinear transformation of an optical beat signal. A totally integrated
      all-optical fiber source of a 59.1-GHz train of 2.2-ps solitons is demonstrated
      with a CDPF. For a beat signal generator we use a dual-frequency erbium fiber
      laser incorporating fiber grating reflectors that provides 16-kHz linewidths and
      a low phase noise of optical beating (< 5 x 10(-5)). Significant suppression of
      stimulated Brillouin scattering, which is essential for this technique, is
      achieved in the CDPF.

PMID- 19844366
TI  - Tunable in-line fiber-optic bandpass filter.
AB  - An in-line fiber-optic bandpass wavelength filter has been demonstrated based on
      a single-mode fiber, side polished into the core, in evanescent contact with a
      high-index multimode overlay waveguide. Passband linewidths down to 5.2 nm were
      observed, while spacing between transmission peaks was seen to range from 45 to
      256 nm for variation of the overlay waveguide parameters. Additionally, rejection
      ratios of >20 dB and insertion losses as low as 0.5 dB were observed.

PMID- 19844367
TI  - Generation of a train of solitons with arbitrary phase difference between
      neighboring solitons.
AB  - We suggest a method that permits generation of a train of solitons with an
      arbitrary phase difference between adjacent pulses in a single-mode optical
      fiber. Specifically, a sequence of solitons in quadrature (i.e., where successive
      pulses differ in phase by pi/2) can permit high-bit-rate transmission. It is
      shown that this train of pulses has advantages for use in optical transmission
      lines as a premodulated sequence of pulses because neighboring solitons in the
      train neither attract nor repel. The case in which this train of pulses is
      generated in an optical fiber with gain is also considered.

PMID- 19844368
TI  - Theory of radiation-induced absorption in optical fibers.
AB  - A new and simple mathematical model for describing radiation-induced absorption
      in optical fibers is presented. This model treats the radiation-induced defect
      generation and the decay process as a series of superposable infinitesimal growth
      and decay events. Unlike the existing power-law growth equation, the new equation
      is nonempirical, dose-rate dependent, and describes both the growth and the decay
      of the induced defect. In the case of constant dose rate the general equation
      reduces to a simple analytical form that agrees reasonably well with the
      experiment.

PMID- 19844369
TI  - Efficient, diode-laser-pumped, diode-laser-seeded, high-peak-power Nd:YLF
      regenerative amplifier.
AB  - Optical amplification of 11 orders of magnitude in a microlens-collimated, diode
      laser-pumped regenerative amplifier has been demonstrated. The amplifier was
      seeded with 20-ps pulses from an FM mode-locked oscillator and with 0.9-ns pulses
      from a modulated diode laser. Seed pulses from both sources were amplified to
      energies exceeding 2.5 mJ. With the thermoelectric coolers and the Pockels cell
      electronics neglected, the diode-seeded system exhibited an electrical-to-optical
      efficiency of 2.2%.

PMID- 19844370
TI  - Aperture guiding in quasi-three-level lasers.
AB  - Aperture guiding, as opposed to thermal waveguiding, is shown to be the dominant
      mechanism for cavity mode stabilization in a quasi-three-level Yb:YAG laser in a
      flat-flat resonator. Excellent agreement is obtained between the experimental and
      modeled spot sizes in this laser when aperture guiding is included in the model.
      The models show that the spot size is insensitive to the exact form of the
      dependence of the transmission of the aperture on the transverse dimension. This
      finding is expected to affect other quasi-three-level lasers.

PMID- 19844371
TI  - Generation of single-frequency radiation at 1064, 1319, and 659.5 nm with an all
      solid-state, out-of-plane Nd:YAG ring laser.
AB  - Single-frequency output from a unidirectional, out-of-plane, all-solid-state
      Nd:YAG ring resonator is demonstrated; the setup can be readily operated at both
      1064 and 1319 nm with an end-pumping configuration. High multimode slope
      efficiencies of 42% were observed at 1064 nm, giving a maximum output power of
      1.32 W. A maximum single-frequency, TEM(00) output at 1319 nm of 650 mW was
      achieved with initial slope efficiencies of 17%. External enhancement cavity
      frequency doubling in LiB(3) O(5) gave a total single-frequency, TEM(00) output
      power of 18 mW at 659.5 nm.

PMID- 19844372
TI  - Beam-mode calculations of a strongly pumped solid-state rod laser with an
      unstable resonator.
AB  - A polarization-sensitive two-dimensional wave-optics simulation was constructed
      to handle the birefringence of strongly pumped solid-state rods. The simulation
      showed that 1.2 times diffraction-limited high-quality beams can be generated
      from a strongly pumped solid-state rod by use of an unstable resonator without
      degradation of the beam quality by the thermally induced birefringence in the
      rod.

PMID- 19844373
TI  - High-power wavelength converters with feedback.
AB  - We have shown theoretically and experimentally that very high conversion
      efficiencies can be obtained in high-peak-power wavelength converters utilizing
      small amounts of feedback, at fluences similar to the no-feedback case. Maximum
      efficiencies are obtained with radially varying reflectivity profiles. We have
      demonstrated the concept, using second-harmonic generation in a deuterated
      potassium dihydrogen phosphate crystal in which 70% energy conversion was
      obtained, in agreement with simulation results. Energy conversion efficiencies of
      56% were also obtained in a beta-barium borate optical parametric oscillator.

PMID- 19844374
TI  - Measurements of the self-starting threshold of Kerr-lens mode-locking lasers.
AB  - We measured the self-starting threshold of passive Kerr-lens mode-locking dye
      lasers and Ti:sapphire lasers by varying the concentration of the intracavity
      dilute-dye saturable absorbers that start the mode locking. From the threshold
      absorber concentration, we determined the strength of the intracavity pulse
      broadening effects that counteract the pulse-shortening mechanisms in the self
      starting stage. Experimental results agree well with theories based on phase
      diffusion and mode pulling.

PMID- 19844375
TI  - Femtosecond-pulse-driven, electron-excited XUV lasers in eight-times-ionized
      noble gases.
AB  - We propose three XUV laser schemes in the 30-50-nm wavelength region that can be
      driven by 10-Hz ultrashort-pulse terawatt laser systems. Tunneling ionization by
      circularly polarized radiation produces both the ions and hot electrons necessary
      to excite the upper laser level.

PMID- 19844376
TI  - Generation of 13-fs, 5-MW pulses from a cavity-dumped Ti:sapphire laser.
AB  - We report on a cavity-dumped self-mode-locked Ti:sapphire laser operating on a 10
      fs time scale. Pulses with energies exceeding 60 nJ and peak powers of 5 MW were
      generated at repetition rates as high as 200 kHz. On injection of the output of
      this laser into a fiber, a white-light continuum is produced that shows great
      potential for compression.

PMID- 19844377
TI  - Blind deconvolution of images by use of neural networks.
AB  - A novel technique for the blind deconvolution of an image from an unknown
      blurring function is presented. This iterative technique consists of two steps.
      We first estimate the blurring function and then use this result to estimate the
      original image. The problem is posed in terms of successive interlinked energy
      minimizations that are mapped onto two Hopfield neural networks.

PMID- 19844378
TI  - Conjugation fidelity and reflectivity in photorefractive double phase-conjugate
      mirrors.
AB  - We present an experimental study of the behavior of photorefractive double phase
      conjugate mirrors that illustrates recent theoretical predictions. We observe a
      sharp fidelity threshold that significantly depends on the specific feature size
      in the input beams. Furthermore, we find that if the two input beams have unequal
      intensities the conjugation process is asymmetric and the steady-state fidelity
      is better on the side of the crystal on which the more-intense beam enters.

PMID- 19844379
TI  - Observations of predicted cooperative shifts in optically pumped stimulated
      emissions in Xe.
AB  - In a recent study Garrett showed that stimulated emissions can be suppressed and
      shifted under the influence of a wave-mixing interference [Phys. Rev. Lett. 70,
      4059 (1993)]. We observe the predicted pressure-dependent frequency shifts in
      optically pumped stimulated emissions from Xe.

PMID- 19844380
TI  - Autocorrelation evaluation from clipped photon detection.
AB  - We present two new techniques for estimating the autocorrelation function, based
      on the measurement of the mean number of clipped photocounts and on the
      calculation of the second-order factorial moment of a series of clipped data. The
      first procedure has the advantage of simplicity, although it produces a poor
      signal-to-noise ratio. On the other hand, the second technique gives a very good
      signal-to-noise ratio, when compared with other known methods.

PMID- 19844381
TI  - Optical multimode frequency-domain reflectometer.
AB  - A multimode laser can instantaneously generate a carrier frequency of
      significantly wide band. The proposed systems, composed of a free-running
      multimode laser diode, an optical spectrometer, and a computing system for fast
      Fourier transformation, can easily provide the potential for ultrahigh resolution
      of the order of 10 microm without scanning frequencies as in frequency-domain
      reflectometers of either the continuously or the stepwise-swept variety.

PMID- 19844382
TI  - Optical coherence microscopy in scattering media.
AB  - We describe a novel technique, based on optical coherence tomography, for
      enhanced optical sectioning in confocal microscopy. Confocal imaging deep into
      highly scattering media is demonstrated and compared with the predictions of a
      single-backscatter theory.

PMID- 19844383
TI  - Distributed temperature-change sensor based on Rayleigh backscattering in an
      optical fiber.
AB  - A frequency-modulated continuous-wave technique is used to detect the presence of
      frequency shifts in the Rayleigh-backscattered light in a single-mode optical
      fiber as a result of a changing temperature. The system is able to detect a rate
      of temperature change of 0.014 K/s, when a 20-cm length of fiber is heated. The
      system is also able to demonstrate a spatial resolution of better than 15 cm.

PMID- 19844384
TI  - Chirp-compensated autocorrelation of optical pulses: erratum.
AB  - An electro-optic phase modulator, rather than a grating pair, is required for
      phase compensation in the chirp-compensated autocorrelator.

PMID- 19844385
TI  - Profilometry of a gastrointestinal surface by an endoscope with laser beam
      projection.
AB  - An active triangulation method that uses an endoscope with laser beam projection
      is proposed for measuring the profile of a gastrointestinal surface. When a laser
      beam is projected onto an object surface in a given direction, the coordinates of
      the beam spot in an endoscope image are uniquely related to the distance from the
      endoscope to the surface. This relation is investigated experimentally, and the
      results are presented in a look-up table. By calibration of the image with this
      look-up table, a profile measurement with high precision is realized. Results of
      experiments with both a test object with known dimensions and a sample extracted
      from a real stomach are described.

PMID- 19844386
TI  - Enhanced backscattering from a one-dimensional rough dielectric film on a glass
      substrate.
AB  - We have observed the enhanced backscattering of light from a characterized
      dielectric film deposited upon a glass substrate when the light illuminates the
      rough surface from the vacuum. The vacuum-dielectric interface is one
      dimensional, randomly rough, while the dielectric-glass interface is
      approximately planar. Numerical and experimental studies reveal that the main
      mechanism responsible for the enhanced backscattering is the constructive
      interference between two waves that follow reciprocal scattering paths through
      the dielectric film, which is also strengthened by the multiple scattering from
      the rough vacuum-dielectric interface.

PMID- 19844387
TI  - Analysis of a coupled absorptive Fabry-Perot resonator in a passive-active
      configuration.
AB  - I present a theoretical analysis and study of a compound Fabry-Perot resonator
      consisting of two coupled Fabry-Perot etalons. The coupled resonator
      configuration studied contains a passive and nonabsorptive Fabry-Perot cavity
      coupled to an active Fabry-Perot cavity, the absorption of which can be adjusted.
      Mathematical relationships useful in the design and optimization of the
      structures with prescribed properties for device applications are given.

PMID- 19844389
TI  - Strongly coupled nonlinear parametric solitary waves.
AB  - We derive conditions under which solitary simulton waves can propagate in
      chi((2)) parametric waveguides. These conditions can occur both with and without
      the use of phase matching.

PMID- 19844388
TI  - Mechanism transformation with wavelength of self-pumped phase conjugation in
      BaTiO(3):Ce.
AB  - We report what is to our knowledge the first observation of mechanism
      transformation with wavelength of self-pumped phase conjugation (SPPC) in
      BaTiO(3):Ce crystals in the near infrared. It was found that the SPPC mechanism
      changed from a backscattering and four-wave-mixing mechanism to a cat mechanism
      when the pump wavelength was varied from 706 to 770 nm. In addition, SPPC was
      obtained when the pump beam entered the crystal by the +c face, and a variation
      with wavelength of optical beam paths in the crystal was also observed.

PMID- 19844390
TI  - Ionization-front soliton in x-ray-stimulated Raman scattering.
AB  - We predict solitonlike pulses and precursors at the Stokes frequency in
      stimulated electronic Raman scattering at the photoionization front of pumping x
      ray radiation. We find two different solitonlike patterns that depend on
      different photoionization mechanisms.

PMID- 19844391
TI  - N-soliton interaction in optical fibers: the multiple-pole case.
AB  - We present an exact solution of the nonlinear Schrodinger equation that describes
      various interactions of N pulses of equal amplitudes.

PMID- 19844392
TI  - Quasi-phase-matched second-harmonic generation from asymmetric coupled quantum
      wells.
AB  - Optical second-harmonic generation of visible light in a superlattice of
      asymmetric coupled GaAs quantum wells has been measured for the first time to our
      knowledge. The orientation of the asymmetric quantum wells was periodically
      reversed such that the quantum-well contribution to the radiated second-harmonic
      signal was quasi-phase matched when it was excited by a lambda = 1.319 microm
      fundamental in the reflection geometry. The second-harmonic intensity generated
      in this superlattice was approximately 3.6 times that generated in a homogeneous
      GaAs reference. The measured superlattice second-harmonic susceptibilities
      are[Equation] and[Equetion].

PMID- 19844393
TI  - Enhanced reverse saturable absorption and optical limiting in heavy-atom
      substituted phthalocyanines.
AB  - The reverse saturable absorption and the optical-limiting response of metal
      phthalocyanines can be enhanced by use of the heavy-atom effect. Phthalocyanines
      containing heavy-metal atoms, such as In, Sn, and Pb, show a nearly factor-of-2
      enhancement in the ratio of effective excited-state to ground-state absorption
      cross sections compared with those containing lighter atoms, such as Al and Si.
      In an f/8 optical geometry, homogeneous solutions of heavy-metal phthalocyanines,
      at 30% linear transmission, limit 8-ns 532-nm laser pulses to </=3 microJ (the
      energy for 50% probability of eye damage) for incident energies as high as 800
      microJ.

PMID- 19844394
TI  - High-energy operation of a Co:MgF(2) laser.
AB  - We have generated output energies of 900 mJ at 2050 nm from a pulsed, room
      temperature, normal-mode Co:MgF(2) laser, with average powers as high as 6.5 W.
      Over the range 1800 to 2450 nm we have obtained pulse energies of at least 100
      mJ.

PMID- 19844395
TI  - Silver thiogallate, singly resonant optical parametric oscillator pumped by a
      continuous-wave mode-locked Nd:YAG laser.
AB  - We describe a silver thiogallate (AgGaS(2)) singly resonant optical parametric
      oscillator (OPO), synchronously pumped by a continuous-wave actively mode-locked
      Nd:YAG laser. The OPO is operated with a signal wavelength near 1.319 microm and
      an idler wavelength near 5.505 microm. At optimum output coupling, 100 mW of
      useful signal power and 6 mW of idler power are generated from 625 mW of pump
      power. The pump is mechanically chopped at a 32:1 duty cycle to prevent thermal
      lensing of the AgGaS(2) crystals. Pump depletion is as high as 63%. The signal
      has pulse widths ranging from 45 to 80 ps and spectral widths ranging from below
      0.1 to 0.3 nm. The OPO signal can oscillate over a 2-mm range of round-trip
      cavity-length mismatch.

PMID- 19844396
TI  - All-solid-state actively mode-locked Cr:LiSAF laser.
AB  - We have demonstrated an actively mode-locked Cr:LiSAF laser pumped by 659-nm
      radiation from an intracavity frequency-doubled diode-pumped Nd:YLF laser. The
      laser was tunable from 815 to 915 nm, and pulses of 30-ps duration at an average
      power of 3.5 mW were generated. With further development this all-solid-state
      system will be particularly suitable for the production of femtosecond pulses, by
      the technique of Kerr-lens mode locking.

PMID- 19844397
TI  - High-power second-harmonic generation with picosecond and hundreds-of-picosecond
      pulses of a cw mode-locked Ti:sapphire laser.
AB  - A cw mode-locked Ti:sapphire laser was efficiently frequency doubled with a
      lithium triborate crystal in an external enhancement cavity. Second-harmonic
      output powers of 1.28 W and 860 mW have been generated at 399 nm with fundamental
      pulse widths of 1.5 and 320 ps, respectively. At the 1.5-ps pulse width the
      conversion efficiency was 75%. The spectral width of the 320-ps pulses, produced
      by modification of a laser cavity, is as narrow as the bandwidth of a normal cw,
      multimode, narrow-bandwidth Ti:sapphire laser. The frequency-doubled output can
      be thus used as a high-power, narrow-bandwidth light source in the UV region.

PMID- 19844398
TI  - Cavity standing-wave and gain compression coefficient in semiconductor lasers.
AB  - The gain compression that is due to carrier heating and spectral hole burning is
      concentrated in semiconductor lasers at the antinodes of the cavity standing
      wave. To first order, this enhances in lasers the material gain compression
      coefficient compared to nonresonant amplifiers by the factor 3/2.

PMID- 19844399
TI  - Pulse-length-limited ultrafast pump-probe spectroscopy in a single laser shot.
AB  - We demonstrate a scheme for taking single-shot pump-probe data with femtosecond
      time resolution. Data recorded from a 100-microm-thick dye solution show that
      pulse-length-limited resolution can be achieved readily with 70-fs laser pulses.
      This technique opens the door for the study of irreversible ultrafast processes
      in a wide variety of solids. Also, unlike with conventional techniques, in this
      method multiple-shot data are not affected by shot-to-shot laser intensity
      fluctuations.

PMID- 19844400
TI  - Optical implementation of carry generation for a multiwavelength full adder.
AB  - We propose the implementation of an optical multiwavelength full adder. Several
      optical wavelengths are used to encode the bits of the binary numbers to be added
      so that the broad spectral bandwidth of optical systems can be utilized. We
      demonstrate the carry generation for the proposed optical multiwavelength full
      adder, using a novel scheme of four-wave mixing in photorefractive crystals.

PMID- 19844401
TI  - Time-integrating correlator based on fiber-optic delay lines.
AB  - A time-integrating correlator based on techniques of fiber-optic delay-line
      signal processing is described. We show that the time-integrating architecture
      does not suffer from limitations associated with previously demonstrated space
      integrating fiber-optic correlators. Experimental results from an eight-channel
      time-integrating correlator are presented, demonstrating real-time
      autocorrelation of a 5-MHz square wave. Limitations of the experimental
      correlator are discussed, and an alternative design is proposed, with a potential
      time-bandwidth product of the order of 10(8).

PMID- 19844402
TI  - Fabrication experiment of photorefractive three-dimensional waveguides in lithium
      niobate.
AB  - A technique for fabricating optical waveguides in a lithium niobate crystal is
      studied experimentally. We fabricate straight and curved structures of refractive
      index as the optical waveguides in a volume of the photorefractive crystal by
      scanning a focused laser beam. The experimental results show that the structure
      of refractive-index distribution is complex yet imply guiding of light in the
      part of high refractive index within the fabricated structure.

PMID- 19844403
TI  - Acoustic signal recognition with a photorefractive time-delay neural network.
AB  - We present a photorefractive processor for audio-acoustic signal recognition
      based on the time-delay neural network model of Hopfield and Tank [in Neural
      Models of Plasticity, J. H. Byrne, ed. (Academic, New York, 1989), p. 363-377].
      We demonstrate the recognition of three words by programming the interconnection
      weights of the time-delay network.

PMID- 19844404
TI  - Coherent beam splitter for atoms based on a bichromatic standing light wave.
AB  - We propose a new coherent atomic beam splitter that is based on the induced
      redistribution of photons in the intense field of two collinear standing waves
      with different frequencies. In the dressed-atom approach, we show that this
      scheme can provide a clear large-angle splitting into two components without
      being restricted to the Raman-Nath regime.

PMID- 19844405
TI  - Partial response precoding for parallel-readout optical memories.
AB  - The data density that can be resolved in optical memories is limited by the
      inherent band-limited nature of optical systems. We show how a precoding
      technique used in serial communications, called partial response precoding, can
      be applied to parallel readout optical memories to precompensate for the spatial
      data broadening that occurs as result of this band limiting. We experimentally
      demonstrate a factor-of-15 improvement in average worst-case contrast ratio and
      an order-of-magnitude improvement in average contrast ratio. Over 50% more area
      was needed to achieve the same contrast ratio in a system without precoding.

PMID- 19844406
TI  - Time-to-space mapping of femtosecond pulses.
AB  - We report time-to-space mapping of femtosecond light pulses in a temporal
      holography setup. By reading out a temporal hologram of a short optical pulse
      with a continuous-wave diode laser, we accurately convert temporal pulse-shape
      information into a spatial pattern that can be viewed with a camera. We
      demonstrate real-time acquisition of electric-field autocorrelation and cross
      correlation of femtosecond pulses with this technique.

PMID- 19844407
TI  - Picosecond degenerate four-wave mixing on potassium in a methane-air flame.
AB  - We demonstrate that picosecond mode-locked laser-based degenerate four-wave
      mixing can be detected with good signal-to-noise ratios in an optically thin
      flame and that detailed turbulence statistics can be acquired by use of this
      technique. A regeneratively mode-locked Ti:sapphire laser was tuned to the
      4(2)S((1/2))-4(2)P degrees ((1/2)) transition in atomic potassium (which was
      doped into the flame) at 769.9 nm. Using the all-forward degenerate four-wave
      mixing geometry, we achieved signal-to-noise ratios of 70:1 without the use of a
      spatial filter. A sensitivity curve and a method for acquiring turbulence
      statistics are presented.

PMID- 19844408
TI  - High-resolution liquid-crystal phase grating formed by fringing fields from
      interdigitated electrodes.
AB  - We report the formation of thin anisotropic phase gratings in a nematic liquid
      crystalline film by use of lateral (fringing) electric fields induced by
      transparent interdigitated electrodes. These gratings yield high diffraction
      efficiency (>30%) with a strong dependence on the readout beam incidence angle.
      In addition, the formation of a defect wall is observed that has a significant
      effect on the diffraction properties of the phase grating.

PMID- 19844409
TI  - Thermal-defocusing/scattering optical limiter.
AB  - Operation of an f/5 thermal-defocusing/scattering optical limiter is described.
      Thermal-defocusing limiting of 6-ns-duration, 532-nm laser pulses occurs by use
      of the broadband-absorbing dye Nigrosin dissolved in carbon disulfide. Additional
      limiting due to thermally induced scattering occurs at high incident fluences
      (above a threshold fluence) when either surface-roughened BASF-1 glass windows
      are in contact with the dye solution or microscopic glass fibers are added to the
      liquid cell. Limiter figures of merit are improved by factors of 2 and 4,
      respectively, over that of a purely thermal-defocusing limiter.

PMID- 19844410
TI  - Two-mode fiber-optic bending sensor with temperature and strain compensation.
AB  - A temperature- and strain-compensated two-mode fiber-optic bending sensor is
      presented. This sensor has the unique ability to measure bending over complex and
      arbitrary paths, using a strictly passive sensing tether. Experimental evidence
      demonstrates the properties of the sensor and the effectiveness of the
      compensation technique.

PMID- 19844411
TI  - Optical-axis perturbation singularity in an out-of-plane ring resonator.
AB  - I use a matrix approach to determine the optical-axis perturbation sensitivity of
      an out-of-plane stable ring resonator. It is found to have a singularity for
      certain design parameters. On one side of the singularity the cavity behaves
      abnormally: the longer the mirror radius, the larger the mode volume and,
      surprisingly, the less the perturbation sensitivity. This is opposite the
      behavior of conventional stable resonators, a finding that is important to the
      cavity designs of out-of-plane ring lasers.

PMID- 19844412
TI  - Generation of optical Haar wavelets by zone plates.
AB  - Optical Haar wavelets are generated by zone plates that are designed to realize
      the bipolar nature of Haar wavelets. We present a circular Haar wavelet in two
      dimensional space, which can extract the edge and corner features simultaneously,
      and characterize its properties with computer simulations. A comparison with
      rectangular Haar wavelets is also given.

PMID- 19844413
TI  - Space-filling modular optics.
AB  - Repeated folding of the optical axis can be used to design space- and volume
      efficient optical systems. We suggest that space-filling curves, such as the
      Peano and Hilbert curves, offer a useful way of realizing compact modular optics.

PMID- 19844414
TI  - Measurements of the effect of surface roughness on the polarization state of
      thermally emitted radiation.
AB  - Infrared measurements are presented of the degree of linear polarization of
      thermally emitted radiation from metallic and glass surfaces. Both types of
      surface show a rapid increase with target angle of the degree of linear
      polarization and a rapid fall with increasing surface roughness.

PMID- 19844415
TI  - Single-frame blind deconvolution by means of frame segmentation.
AB  - For restoration of an image degraded with a shift-invariant point-spread function
      (PSF), partial images segmented from the degraded image are blind deconvolved in
      parallel for estimation of the common PSF in each partial image. An object
      function is reconstructed by deconvolution of the whole image with the PSF. A
      technique for calibrating contamination caused by the segmentation is developed.
      Results for a computer-generated image and an atmospherically degraded solar
      image are presented.

PMID- 19844416
TI  - Soliton interaction in the presence of a weak nonsoliton component.
AB  - We study both experimentally and theoretically soliton interaction in the
      presence of a weak nonsoliton component and show that the existence of a
      frequency-shifted cw wave results in a temporal shift of the soliton.

PMID- 19844417
TI  - High second-order nonlinearities in poled silicate fibers.
AB  - Effective quadratic nonlinearities as high as 0.2 pm/V are reported for the first
      time to our knowledge in poled germanosilicate fibers. This value is ~200 times
      higher than previously achieved in these fibers. The presence of Ge is found to
      enhance the efficacy of both thermal (in combination with OH doping) and electron
      beam poling in silica.

PMID- 19844418
TI  - Measurement of timing jitter in filter-guided soliton transmission at 10 Gbits/s
      and achievement of 375 Gbits/s-Mm, error free, at 12.5 and 15 Gbits/s.
AB  - We report on extensive measurement, as a function of distance, of the timing
      jitter in sliding-frequency-filterguided soliton transmission at 10 Gbits/s. The
      measured jitter is separated into a sliding-filter-damped, Gordon-Haus term, a
      similarly damped acoustic term, and a recently predicted contribution from
      scatter in pulse polarizations. Measured error-free (bit-error rate <10(-10))
      distances at 10, 12.5, and 15 Gbits/s are 35, 30, and 25 Mm, respectively.

PMID- 19844419
TI  - Bending-induced loss in dual-mode rectangular waveguides.
AB  - We examine how the bending-induced mode losses in a dual-mode rectangular-core
      waveguide vary with bend orientation. Bending about the minor axis [case (i)] and
      bending about the major axis [case (ii)] are considered. The second (LP(11)) mode
      is more lossy in case (i) than in case (ii), while the reverse is true for the
      first (LP(01)) mode. Further, in case (i) the LP(11)-mode loss is larger than the
      LP(01)-mode loss, but in case (ii) the LP(01)-mode loss is, surprisingly, larger
      than the LP(11)-mode loss. LP(11)-mode loss is consistent with the recent
      experimental results. This study should be useful in designing efficient
      elliptical-core fiber components such as LP(11)-mode strippers based on
      differential mode loss of the first two modes.

PMID- 19844420
TI  - Optical waveguides fabricated in anodic alumina films.
AB  - The transmittance of an anodic alumina film changes significantly with the
      refractive index of the guest material that is contained in columnar pores. We
      fabricated a channel waveguide with a Y junction in an alumina film by filling
      the pores with photocurable resins of suitable refractive indices.

PMID- 19844422
TI  - Multiwavelength fiber laser using a spatial mode beating filter.
AB  - A multiwavelength comb is obtained from Er(3+) - and Nd(3+)-doped fiber lasers by
      incorporation of a section of multimode optical fiber into an otherwise single
      mode fiber ring cavity. This combination of fiber types acts as a wavelength
      dependent filter in the laser through spatial mode beating between the LP(01) and
      LP(11) modes in the multimode fiber.

PMID- 19844421
TI  - High-power green-beam generation in continuous-wave modes by use of long
      KTiOPO(4) crystals with a Nd:YAG laser.
AB  - We report the generation of 24-W green power, which, to our knowledge, is the
      highest level of green power achieved in cw modes. Intracavity frequency doubling
      of a simple Nd:YAG laser was performed with a 15-mm KTiOPO(4) crystal. The green
      power was stable, and the highest level of green power achievable was limited
      only by the maximum lamp input power. We obtained a similar level of green power
      by replacing the single 15-mm KTiOPO(4) crystal by a phase-unified multinonlinear
      crystal combination consisting of a 5-mm and a 10-mm KTiOPO(4) crystal.

PMID- 19844423
TI  - Efficient room-temperature CO laser with high specific output.
AB  - Efficient room-temperature operation of a fast-axial-flow rf-discharge-excited CO
      laser is described. A steady-state laser output of 268 W has been obtained with a
      CO/N(2)/He/Xe/O(2) mixture from a 19-mm-diameter, 300-mm-long discharge. The
      corresponding electrical conversion efficiency and the specific laser output are
      as high as 13.5% and 3.15 W/cm(3), respectively. The role of Xe in the mixtures
      is discussed. The specific laser output achieved is comparable with those of the
      high-power industrial CO(2) lasers in which a similar excitation scheme is
      applied.

PMID- 19844424
TI  - Self-starting, self-mode-locked Ti:sapphire laser.
AB  - Self-starting of a self-mode-locked Ti:sapphire laser has been demonstrated,
      without any additional elements other than those necessary for self-mode locking.
      This self-starting is attributed to a gain saturation lens, as with self-mode
      locking to a Kerr lens. I achieve the self-starting by optimizing and cascading
      the cavity loss modulation induced by the gain saturation lens and the Kerr lens.
      Stable pulses shorter than 100 fs in duration are obtained at a wavelength near
      840 nm.

PMID- 19844426
TI  - Ultrahigh-frequency stabilization of a diode-pumped Nd:YAG laser with a high
      power-acceptance photodetector.
AB  - We describe the ultrahigh-frequency stabilization of a diode-pumped Nd:YAG laser
      by use of a high-poweracceptance photodetector. The photodetector, which is
      constructed with an optical power divider and eight combined photodiodes, is
      developed to reduce shot-noise-limited FM noise. The laser frequency is locked to
      a Fabry-Perot cavity with a finesse of 25,600 by the Drever-Hall technique. By
      using the optical power of 47 mW at the photodetector, we reduce the relative FM
      noise at the error signal to the shot-noise limit of 4.2x10(-5) Hz/ radicalHz
      below the Fourier frequency of 500 Hz.

PMID- 19844425
TI  - High-power mode-locked hybrid pulse source using two-section laser diodes.
AB  - We describe a mode-locked hybrid pulse source with a two-section laser diode to
      obtain short mode-locked pulses (23 ps) with an average power of 7.8 mW, a high
      peak power of 137 mW, and a repetition rate of 2.51 GHz. The hybrid laser
      incorporates a two-section laser and an optical fiber cavity with an integrated
      Bragg reflector. The Bragg reflector controls the operating wavelength to
      subnanometer precision and also confines the bandwidth of the pulses so as to
      keep the time-bandwidth product below 1.

PMID- 19844427
TI  - Carrier deficit from the nominal threshold density and mode-suppression ratio of
      an above-threshold biased semiconductor laser.
AB  - An analytical expression for the carrier deficit DeltaN from the nominal
      threshold carrier density N(t) of an above-threshold biased semiconductor laser
      has been deduced. As a result, both the mode spectra and the mode-suppression
      ratio of a semiconductor laser can be studied analytically. The measured
      dependence of the mode-suppression ratio on the wavelength difference between the
      gain peak and its nearest cavity mode of the semiconductor laser confirms the
      theoretical predictions.

PMID- 19844428
TI  - 250-fs optical pulse generation by simultaneous soliton compression and shaping
      in a nonlinear optical loop mirror including a weak attenuation.
AB  - We report the generation of 30-W peak-power 250-fs-wide pedestal-free optical
      pulses at 1.54 microm by use of a chirpcompensated optically amplified
      semiconductor laser followed by simultaneous soliton compression and shaping
      within a nonlinear optical loop mirror. A weak controllable attenuation is
      inserted within the loop to permit precise control of the pulse shape. Pedestal
      free pulses are obtained after optimization of both the fiber length and the
      power balance between the counterpropagating pulses within the loop. The
      corresponding spectrum reveals a twofold split structure that is due to a
      residual chirp from self-phase modulation.

PMID- 19844429
TI  - Femtosecond laser pulse shaping by use of microsecond radio-frequency pulses.
AB  - We demonstrate a new pulse-shaping technique, using an acousto-optic modulator as
      a spatial modulator in a zero-dispersion delay line. Compared with existing
      techniques, this approach simplifies optical alignment and dramatically improves
      update rates. It should also improve flexibility for generating complex
      waveforms.

PMID- 19844430
TI  - Transmitted photon intensity through biological tissues within various time
      windows.
AB  - The intensity of the early-arriving snake portion of 100-fs ultrashort laser
      pulses transmitted through biological tissue of increasing thickness was measured
      by a streak camera. The snake photon intensity within the first arrival time
      interval Deltat was found to decrease exponentially with tissue thickness (z) as
      I(Deltat) = I(0)A exp[-b(Deltat)z/l(t)], where I(0) is the incident laser pulse
      intensity, l(t) is the transport mean free path of the medium, and the parameters
      b and A depend on the time interval Deltat. This result shows that the intensity
      of snake photons decays significantly more slowly than that of ballistic photons
      as tissue thickness increases.

PMID- 19844431
TI  - Photorefractive mixing of amplitude-modulated signals.
AB  - We analyze the circumstances under which a real-time hologram written with
      amplitude-modulated beams behaves as a linear mixer. We calculate nonlinear
      correction terms that can be used to analyze the linearity of a variety of
      photorefractive time-integrative devices.

PMID- 19844432
TI  - Photon-echo interferometry.
AB  - Temporal interference between photon echoes of adjacent transitions in simple
      atoms is demonstrated, yielding suppression of the echo intensity by a factor of
      10(4). The method provides a sensitive probe of perturbations that differentially
      affect the phase of the dipole moments for the adjacent transitions.

PMID- 19844433
TI  - Atom galleries for whispering atoms: binding atoms in stable orbits around an
      optical resonator.
AB  - The external fields of optical whispering gallery modes may be used to confine
      atoms in stable orbits around a dielectric microsphere. As an example, a toroidal
      dipole-force trap (atom gallery) for three-level atoms is investigated, and the
      possibility of achieving an atomic (matter-wave) resonator is discussed. The
      extremely small electromagnetic mode volumes and high Q's of the whispering
      gallery modes should permit a circulating photon to be repeatedly absorbed and
      reemitted by a trapped whispering atom.

PMID- 19844434
TI  - Holographic motion picture by Eu(3+):Y(2)SiO(5).
AB  - Real-time recording of a moving object was made with persistent spectral hole
      burning of a cryogenic Eu(3+):Y(2)SiO(5) crystal. In a basic holographic
      configuration the ultrastable laser frequency was continuously scanned within the
      (7)F(0)-(5)D(0) absorption line (typically 200 MHz in 20 s) while the object was
      in motion, thus permitting the storage and reconstruction of the moving image.
      The success of this motion picture is attributable to (1) the kilohertz-wide hole
      width, (2) the quasi-persistent hole lifetime, and (3) the high hole-burning
      quantum efficiency of this material.

PMID- 19844435
TI  - Optical detection of ultrasound with a microchip laser.
AB  - A novel optical ultrasonic detector that relies on frequency modulation of a
      microchip laser is proposed and demonstrated. When the laser is placed in a time
      varying acoustic field, the microchip laser cavity length is periodically
      modulated, creating a frequency-modulated optical output in which the frequency
      shift is linearly proportional to the acoustic-wave amplitude. With a confocal
      Fabry-Perot slope filter and a Nd:YAG microchip laser operating at 1.06 microm, a
      detector response of 7.5 MHz/kPa was measured at an acoustic frequency of 7.75
      MHz. A one-dimensional acoustic model is developed to explain the observed
      detector performance.

PMID- 19844436
TI  - High-speed analog achromatic intensity modulator.
AB  - We report what is to our knowledge the first implementation of a broadband analog
      intensity modulator composed of two chiral smectic liquid-crystal half-wave
      retarders. A reflection-mode intensity modulator employing a single active device
      has also demonstrated achromatic transmission. A quantitative theory for
      chromatic compensation is presented. By optimum selection of liquid-crystal
      retardance and orientation, intensity transmission is uniform throughout the
      visible. The chiral smectic liquid-crystal devices used in the implementation are
      capable of switching in less than 20 micros.

PMID- 19844437
TI  - Integrated ultrafast saturable absorber.
AB  - An ultrafast saturable absorber was demonstrated experimentally in AlGaAs,
      operated with a photon energy below half the band gap, near 1555 nm. Both the
      saturation intensity and the linear transmission can be independently designed in
      the structure. The device is based on spatial soliton emission from a tapered
      channel waveguide with a corresponding increase in transmission of 50%. The
      experimental data compare favorably with numerically simulated results.

PMID- 19844438
TI  - Phase matching for large-scale frequency upconversion in plasma: erratum.

PMID- 19844439
TI  - Expression of the kernel of a fractional Fourier transform in elementary
      functions.
AB  - The problem of expressing the kernel of a fractional Fourier transform in
      elementary functions is posed and solved.

PMID- 19844440
TI  - Control of wave-front propagation with diffractive elements.
AB  - In principle, diffractive elements can be designed to control a propagating wave
      in three dimensions, but no general procedure has been proposed. We present an
      iterative method that is suitable for the design of such diffractive elements.
      The resulting complex amplitude distribution will approach any arbitrary
      requirement, as much as is permitted by basic physical principles. The problem of
      "nondiffracting-beam" propagation is analyzed as a special case, and intensity
      peaks are generated that propagate as much as 4 m with a bounded width. The
      generality of the method, as compared with other techniques, is beams.

PMID- 19844441
TI  - Optical phase-lock loops with photoconductive semiconductor phase detectors.
AB  - Photoconductive semiconductors that contain deep-level traps can be used as
      optical phase detectors because of the photocurrents generated by moving space
      charge electric fields formed inside the material by transient optical
      interference patterns. Two narrow-linewidth Nd:YAG nonplanar ring oscillator
      lasers were successfully phase locked with InP:Fe, GaAs:Cr, GaAs, and CdTe:V
      crystals used as optical phase detectors.

PMID- 19844442
TI  - Spectral transmission properties of a self-similar optical Fabry-Perot resonator.
AB  - The spectral transmission properties of a self-similar optical Fabry-Perot
      resonator are theoretically studied. The structure considered can be realized by
      alternation of two dielectric layers of different refractive indices such that
      the highest refractive-index layers belong to a triadic Cantor set. The
      transmission spectrum exhibits localized peaks inside forbidden frequency band
      gaps. This feature could be useful in the design of novel filters. Moreover the
      self-similarity of the structure is reflected in a weak self-similarity in the
      transmission spectrum. A comparison with a regular periodic structure is also
      presented.

PMID- 19844443
TI  - Breaking the diffraction resolution limit by stimulated emission: stimulated
      emission-depletion fluorescence microscopy.
AB  - We propose a new type of scanning fluorescence microscope capable of resolving 35
      nm in the far field. We overcome the diffraction resolution limit by employing
      stimulated emission to inhibit the fluorescence process in the outer regions of
      the excitation point-spread function. In contrast to near-field scanning optical
      microscopy, this method can produce three-dimensional images of translucent
      specimens.

PMID- 19844444
TI  - Long-pulse self-starting stimulated-Brillouin-scattering resonator.
AB  - We demonstrate, for the first time to our knowledge, a self-starting stimulated
      Brillouin-scattering phaseconjugate resonator in a flash-lamp-pumped dye-laser
      system. The brightness of the laser is increased by a factor of 40 compared with
      that of an equivalent plane-]plane conventional resonator.

PMID- 19844445
TI  - Origin of negative chi((3)) in squaraines: experimental observation of two-photon
      states.
AB  - Femtosecond pump-probe experiments performed on squaraines demonstrate strong
      couplings between the first excited state and high-lying two-photon states. The
      experimental data agree well with our earlier quantum many-electron calculations
      based on multiple-excited configuration interactions. We show that high-lying
      twophoton states in squaraines are critically important to understanding the
      observed third-order optical properties and that two-level models are inadequate
      even for molecules with negative third-order optical susceptibilities.

PMID- 19844446
TI  - Short-pulse conical emission and spectral broadening in normally dispersive
      media.
AB  - The nonlinear Schrodinger equation predicts conical emission that is due to
      spatiotemporal propagation of short pulses in normally dispersive, cubically
      nonlinear media. This effect is a direct consequence of a four-wave interaction.

PMID- 19844447
TI  - Nonlinear mirror mode locking of a cw Nd:YLF laser.
AB  - Passive mode locking of a cw lamp-pumped Nd:YLF laser with the nonlinear mirror
      technique is reported. Nearly transform-limited pulses of 13-ps duration and 1.5
      W average power at 1.047 microm have been obtained. The nonlinear mirror consists
      of a lithium triborate frequency-doubling crystal and a dichroic mirror with high
      reflectivity for the second harmonic and lower reflectivity for the fundamental
      frequency. The mode-locking process is self-starting, with pulse duration and
      stability strongly dependent on the cavity parameters.

PMID- 19844448
TI  - Precise control of the center wavelength and bandwidth of wavelength-selective
      single-mode fiber couplers.
AB  - Low-loss asymmetrical single-mode fiber wavelength-selective directional couplers
      are fabricated at low cost. Proper control of the remaining cladding thickness
      and the interaction length of the half-couplers produces exactly the required
      bandwidth and center wavelength of the filter. Increasing the interaction length
      reduces the bandwidth and the sidelobes. Calculated values show good agreement
      with the experimental results.

PMID- 19844449
TI  - Normal-incidence grating couplers in Ge-Si.
AB  - We report a normal-incidence grating coupler that is monolithically integrated
      with a Ge(x)Si(1-x) rib waveguide. The design, fabrication, and testing
      procedures are described for a 0.33-microm-period grating coupler integrated with
      a Ge(0.04)Si(0.96) waveguide. Also, a theoretical analysis based on coupler-mode
      theory has been carried out to predict the coupling efficiency and its dependence
      on the angle of incidence of light. For normal incidence the measured efficiency
      of 6.5% was found to be in good agreement with the theoretical prediction of
      6.9%. The measured FWHM of the acceptance angle about the normal was 5 degrees ,
      compared with the theoretical prediction of 3 degrees .

PMID- 19844450
TI  - Tunable erbium fiber laser using a novel overlay bandpass filter.
AB  - A unidirectional erbium fiber laser incorporating a novel LiNbO(3) overlay fiber
      optic bandpass filter is demonstrated. By applying index-matching oils of
      different refractive indices to the surface of the overlay filter, we could tune
      the operating wavelength of the laser from 1531 to 1556 nm while maintaining a
      bandwidth of less than 0.2 nm (resolution limited). Output powers as high as 3 mW
      for 36 mW of pump power have been recorded.

PMID- 19844451
TI  - Optical and laser properties of (F(2)(+))(H) centers in sulfur-doped NaCl.
AB  - We report the production and main optical and laser properties of (F(2)(+))(H)
      color centers in sulfur-doped NaCl crystals. Using a 1.06-microm Nd:YAG laser as
      the pump source, we realize continuous-wave and synchronously mode-locked laser
      operation. The laser is tunable over a remarkably large wavelength range of 1.43
      2.0 microm. Output power levels are as much as ~800 mW near 1.6 microm; mode
      locked pulse durations are typically 4-7 ps.

PMID- 19844452
TI  - Resonators for Kerr-lens mode-locked femtosecond Ti:sapphire lasers.
AB  - Resonators for Kerr-lens mode-locked lasers are studied with the help of an
      analytical model, and a new design procedure is presented. The experiments
      performed with a femtosecond Ti:sapphire laser demonstrate that this model
      permits an effective resonator design and offers reliable guidelines for the
      final experimental optimization. With a suitable resonator configuration, self
      starting of the Kerr-lens mode-locking regime has been achieved.

PMID- 19844453
TI  - Intracavity frequency doubling of a Nd:YVO(4) laser pumped by a wavelength-locked
      laser diode using a transmission-type optical filter.
AB  - We demonstrate that intracavity frequency doubling of Nd:YVO(4) pumped by a laser
      diode can be stabilized by use of a wavelength-locking system of the laser diode
      with a transmission-type optical filter in a confocal optical configuration. The
      wavelength locking of the laser diode to the peak wavelength of the absorption
      spectrum of Nd:YVO(4) yielded stable green light of 10-mW power for an incident
      pumping power of 55 mW.

PMID- 19844454
TI  - Single-mode electro-optically tuned Nd:YVO(4) laser.
AB  - The design and operating characteristics of a single-mode electro-optically tuned
      Nd-doped YVO(4) laser are described. Tuning is accomplished by means of a section
      of LiTaO(3) included in the 600-microm-long cavity. The laser has been tuned
      electronically over a range of > 10 GHz and thermally over a range of > 100 GHz
      without mode hopping.

PMID- 19844455
TI  - Electric-field-induced quantum coherence of the intersubband transition in
      semiconductor quantum wells.
AB  - An intense coherent laser field couples two electron subbands in quantum wells.
      Using generalized self-consistent density functional theory, we study the nature
      of the Coulomb and light-induced electronic renormalization. We show electric
      field-induced transparency and light amplification without population inversion
      of a weak probe beam in such a system. The effects of the pump field strength,
      electron density, and delta-doping position are investigated.

PMID- 19844456
TI  - Dynamic holographic phase gratings in multiple-quantum-well asymmetric Fabry
      Perot reflection modulators.
AB  - Dynamic holographic pi-phase gratings can be written in a multiple-quantum-well
      asymmetric Fabry-Perot reflection modulator by spatial modulation of the quantum
      confined exciton absorption. Operating near the Fabry-Perot resonance, the phase
      grating quenches the zero-order reflection and enhances the first-order
      diffraction efficiency. The diffraction efficiency of these structures as
      diffractive optics elements is not sensitive to the contrast ratio, which eases
      the constraints for device fabrication. Numerical simulations for multiple
      quantum-well structures are presented that fully include refractive-index changes
      in response to a spatial modulation of the exciton absorption, which can be
      caused by any of several techniques, including free-carrier gratings, absorption
      bleaching, electro-optic effects, and photorefractive effects.

PMID- 19844457
TI  - Photorefractive phase shift induced by nonlinear electronic transport.
AB  - A photorefractive phase shift can be generated under dc applied fields if the
      dominant photocarriers have a nonlinear velocity-field dependence with a
      vanishing differential mobility. Phase shifts as large as pi/2 are possible when
      velocity saturation disables dielectric relaxation while still permitting large
      drift rates. The inability of the space-charge field to relax leads to a
      saturated trap density that mimics trap-limited behavior. All direct-gap
      photorefractive semiconductors have strong velocity saturation from hot-electron
      transport effects, most widely known for the origin of the Gunn effect. Previous
      photorefractive trap-limited-field studies may have to be reevaluated in the
      context of transport nonlinearity.

PMID- 19844458
TI  - Soliton formation in a femtosecond optical parametric oscillator.
AB  - We report evidence for soliton formation in a Ti:sapphire-laser-pumped
      femtosecond optical parametric oscillator. Appropriate conditions of dispersion
      are discussed, and temporal and spectral measurements of the output pulses are
      presented. Quantitative agreement with existing theory is implied.

PMID- 19844459
TI  - Femtosecond soliton generation in a praseodymium fluoride fiber laser.
AB  - We report what is to our knowledge the first femtosecond pulse generation at 1.3
      micro m in a Pr 3(+)-doped fluoride fiber laser. After optimization of the cavity
      length and dispersion, the laser generated pulses as short as 620 fs. We also
      describe self-stabilization and self-organization of the output pulse train at
      repetition rates from the fundamental cavity frequency of 700 kHz up to 440 MHz
      and report on polarization effects.

PMID- 19844460
TI  - Pulse compression in a synchronously pumped optical parametric oscillator from
      group-velocity mismatch.
AB  - We report on experimental intracavity compression of generated pulses (down to
      one quarter of the pumppulse duration) in a widely tunable synchronously pumped
      picosecond optical parametric oscillator. This pulse compression takes place when
      the optical parametric oscillator is well above threshold and is due to the
      pronounced group-velocity mismatch of the pump and oscillating waves in the
      nonlinear crystal.

PMID- 19844461
TI  - Terahertz-rate optical pulse generation from a passively mode-locked
      semiconductor laser diode.
AB  - We report what is to our knowledge the first demonstration of terahertz-rate
      optical pulse generation by harmonic passive mode locking in a distributed-Bragg
      reflector laser diode. Along with the fundamental repetition rate of 38.8 GHz, we
      observed 400-GHz, 800-GHz, and 1.54-THz harmonics, depending on the bias
      condition of gain section. The pulse envelope for 1.54-THz pulses was in good
      agreement with a calculation from the Fourier transformation of the optical
      spectrum, indicating that the output pulses are transform limited.

PMID- 19844462
TI  - Sub-100-fs optical parametric generator pumped by a high-repetition-rate
      Ti:sapphire regenerative amplifier system.
AB  - Infrared light pulses as short as 70 fs that are nearly bandwidth limited are
      obtained in a simple double-pass optical parametric generator with a single beta
      barium borate nonlinear crystal. Tunability in the 1.2-1.3microm range is
      demonstrated with sub-100-fs pulse duration, microjoule pulse energy, and 1-kHz
      repetition rate.

PMID- 19844463
TI  - Ultranarrow (13)C(2)H(2) saturated-absorption lines at 1.5 microm.
AB  - The saturation spectroscopy of molecular transitions at 1.5microm is reported. We
      show that it is possible, with a low-power laser diode, to obtain 2-MHz-wide
      acetylene saturated-absorption lines, and we give what is to our knowledge the
      first experimental estimation of (13)C(2)H(2) saturation intensity. To our
      knowledge, these lines are the narrowest reported 1.5-microm frequency references
      and should be suitable for high-quality 1.5-microm laser frequency standards.

PMID- 19844464
TI  - Synthesis of an arbitrary axial field profile by computer-generated holograms.
AB  - Computer-generated holograms are employed to design any desired intensity
      distribution along the propagation axis for a finite specified distance.

PMID- 19844465
TI  - Nanosecond single-photon timing with InGaAs/InP photodiodes.
AB  - We demonstrate that separate absorption and multiplication InGaAs/InP avalanche
      photodiodes can work biased above the breakdown voltage and detect the arrival
      time of single photons with 1-ns resolution and a noise-equivalent power of 1 x
      10(-14) W/Hz((1/2)) at 150 K. We investigated the performance of various samples,
      cooling the detectors from different temperatures down to 50 K. These devices are
      suitable for the detection of short optical pulses in the near-infrared range up
      to a 1.55-microm wavelength, for the characterization of optical communication
      components, and for luminescence and radiative decay measurements.

PMID- 19844466
TI  - Two-color trapped-particle optical microscopy.
AB  - We demonstrate a method for nonintrusive scanned near-field optical microscopy.
      The microscope utilizes an optical trap to position accurately a 50-100-nm
      diameter lithium niobate particle. The infrared trapping beam is frequency
      doubled in the particle, resulting in a visible microscopic optical probe. By
      separation of the trapping and detection wavelengths, objects that are
      transparent in the infrared (e.g., biological) may be positioned close to the
      particle, resulting in high resolution. The current experimental resolution is
      limited to approximately 500 nm by the properties of the test objects. The
      theoretical resolution is less than 100 nm.

PMID- 19844467
TI  - Nonlinear phase change in type II second-harmonic generation under exact phase
      matched conditions.
AB  - The process of type II second-harmonic generation has been investigated
      theoretically. It is found that, unlike in the process of type I second-harmonic
      generation, phase matching is not necessary for a significant shift of the pump
      wave phase to be produced. The simple inequality of the intensities of
      interacting waves suffices for this effect to occur.

PMID- 19844468
TI  - Polarization-domain solitary waves of circular symmetry in Kerr media.
AB  - We present a new class of dark circularly symmetric solitary wave in bulk, self
      defocusing Kerr media. The waves comprise two orthogonally polarized fields
      mutually guiding each other and forming separate polarization domains. The
      stability of these new solutions and the dynamics of related structures are
      briefly investigated.

PMID- 19844469
TI  - Self-focusing threshold in normally dispersive media.
AB  - The threshold at which self-focusing initially dominates the dynamics of short
      pulse propagation in normally dispersive bulk media, causing an explosive
      increase in peak intensity, is estimated analytically and verified numerically.
      Intensity-dependent propagation effects such as spectral broadening also occur
      explosively at this threshold.

PMID- 19844470
TI  - Transient degenerate four-wave mixing in a saturable Nd:YAG amplifier: the effect
      of pump-beam propagation.
AB  - A transient model of degenerate four-wave mixing in saturable amplifiers is
      developed for calculation of the phase-conjugate reflectivity in the weak-probe
      beam limit. Our model takes into account the laser amplification of all the
      interacting beams together with the wave-mixing process between the two
      counterpropagating pump waves. Experimental investigations are made in a flash
      lamp-pumped Nd:YAG amplifier with nanosecond pulses at 1.06 microm. A
      reflectivity of 22% is achieved when all the waves interfere within the laser
      medium.

PMID- 19844471
TI  - Second-order cascading as the origin of large third-order effects in organic
      single-crystal-core fibers.
AB  - We have identified cascading of second-order nonlinear processes as the origin of
      previously reported, very large nonlinearities measured by self-phase-modulation
      experiments in organic single-crystal-core fibers of 4-(N,N-dimethylamino)-3
      acetamidonitrobenzene.

PMID- 19844472
TI  - Nonlinear-optical studies of molybdenum metal organics.
AB  - We have measured the third-order susceptibility, X((3)), versus concentration for
      a number of molybdenum-based metal-organic complexes in solution, using
      independent degenerate four-wave mixing and Z-scan techniques. Good agreement was
      obtained between the degenerate four-wave mixing and Z-scan measurements. The
      variation of X((3)) with concentration yielded the second-order
      hyperpolarizability gamma. A close correlation was observed between the number of
      delocalized pi electrons and the magnitude of gamma.

PMID- 19844473
TI  - Photodarkening in Tb(3+)-doped phosphosilicate and germanosilicate optical
      fibers.
AB  - The presence of Tb(3+) is found to sensitize greatly phosphosilicate and
      germanosilicate optical fibers to photodarkening when they are exposed to 488-nm
      light. The darkening is a three-photon process and may involve the
      photoionization of Tb(3+) to Tb(4+). This sensitivity raises the possibility of
      side writing refractive-index gratings into silica-based optical fibers with 488
      nm light.

PMID- 19844474
TI  - Experimental demonstration of compression of dispersed optical pulses by
      reflection from self-chirped optical fiber Bragg gratings.
AB  - Dispersion compensation is demonstrated experimentally by pulse compression with
      the use of chirped optical fiber Bragg gratings. The gratings chirp is self
      induced by the Gaussian intensity profile of the 240-nm wavelength beam used for
      holographic sidewriting of the grating. Chirped pulses generated by a 1.55-microm
      gain-switched distributed-feedback laser with an initial pulse duration of 21 ps
      and a spectral width of 0.7 nm are compressed to 13 ps, in good agreement with
      theory.

PMID- 19844476
TI  - Tm(3+):YLF laser continuously tunable between 2.20 and 2.46 microm.
AB  - Room-temperature, continuous-wave laser action at 2.3 microm corresponding to the
      (3)H(4)-(3)H(5) transition in Tm(3+)- doped YLF is achieved. Output powers of 200
      mW and a slope efficiency of 15% have been obtained for a pump power of 2 W at
      0.78 microm. In addition, continuous tunability of this laser from 2.20 to 2.46
      microm is obtained.

PMID- 19844475
TI  - Proton-exchanged periodically segmented waveguides in LiNbo(3).
AB  - We report on the characterization of single-mode and multimode proton-exchanged
      periodically segmented waveguides in lithium niobate. Variation of effective
      indices of different modes for different annealing times as a function of duty
      cycle and period of segmentation is presented. It is shown that the proton
      exchanged periodically segmented waveguide can be modeled by an equivalent z
      invariant depth-independent graded-index waveguide with a Gaussian index
      distribution. Although the depth of the equivalent waveguide is independent of
      duty cycle, the peak refractive-index change increases almost linearly with the
      duty cycle and saturates at large duty cycles. The results should benefit the
      design of linear and nonlinear devices that are based on segmented waveguides.

PMID- 19844477
TI  - Single-mode tunable erbium:ytterbium fiber Fabry-Perot microlaser.
AB  - A compact tunable single-mode fiber laser at 1535 nm is developed by use of a
      novel combination of high-gain erbium:ytterbium (Er:Yb) phosphate-glass fiber
      within a fiber Fabry-Perot cavity. We demonstrate what we believe to be the
      shortest Er:Yb phosphate-glass fiber Fabry-Perot laser ever reported, having a
      100-microm cavity length and a continuous wavelength tuning range over 4.52 nm
      (limited by the sharp fiber gain peak). An alternative three-mirror laser design
      has also demonstrated single-mode lasing operation.

PMID- 19844478
TI  - Three-wavelength device for all-optical signal processing.
AB  - We describe the operation of a semiconductor laser amplifier as a nonlinear
      element, using a novel three-wavelength configuration, which enhances the
      recovery rate of the nonlinear refractive index and permits choice of its sign
      and magnitude. Simple rate-equation analysis suggests that 100-GHz operation
      should be possible with powers of ~1 W.

PMID- 19844479
TI  - Analytical theory of four-wave mixing in semiconductor amplifiers.
AB  - The analytical theory of four-wave mixing in semiconductor amplifiers is
      developed. The theory applies to arbitrary saturation conditions. If carrier
      depletion and spectral hole burning are considered, the conversion efficiency is
      the maximum at a total input power that produces a gain compression of e(-2)
      (approximately -9 dB), independently of the physical parameters of the amplifier.

PMID- 19844480
TI  - Regenerative amplification of 30-fs pulses in Ti:sapphire at 5 kHz.
AB  - 18-fs pulses from a self-mode-locked Ti:sapphire laser are amplified to 60 microJ
      of energy at 4.9 kHz with chirped-pulse amplification in a Ti:sapphire
      regenerative amplifier. After recompression, 30-35-fs, near-transform-limited
      pulses are obtained.

PMID- 19844481
TI  - Generation of 1-ps infrared pulses at 10.6 microm by use of low-temperature-grown
      GaAs as an optical semiconductor switch.
AB  - Using a GaAs layer grown by molecular-beam epitaxy at low substrate temperature
      as an optical semiconductor switch, we demonstrate the generation of picosecond
      infrared pulses at 10.6 microm. To our knowledge, this is the first time that
      ultrashort pulses have been generated by use of only one reflective switch. A
      cross-correlation method, which is used to measure the pulse width, indicates
      that the pulse width is ~1 ps. A 200-nm-thick, low-temperature molecular-beam
      epitaxy-grown GaAs layer, acting as an ultrafast active switching element, was
      grown at a low temperature of 320 degrees C on a GaAs substrate and annealed at
      550 degrees C. The presence of a high density of As precipitates in this material
      that act as fast recombination centers gives the optically injected carriers in
      low-temperature molecular-beam-epitaxy-grown GaAs a lifetime of 0.5 ps. We also
      discuss the feasibility of the extension of this technique to other mid- and far
      infrared lasers.

PMID- 19844482
TI  - Demonstration of a novel three-dimensional autostereoscopic display.
AB  - We report what we believe is the first static implementation of the partial-pixel
      architecture, which provides a conceptual framework for the construction of real
      time three-dimensional displays that are functionally equivalent to holographic
      stereograms (i.e., the simultaneous display of a series of stereoscopic images).
      The device is physically realized as a set of amplitude diffraction gratings on a
      chrome mask that was fabricated by standard photolithographic techniques. The
      intended three-dimensional object encoded in the display was strikingly visible
      on readout with an incoherent illumination source.

PMID- 19844483
TI  - Spectroscopy of Dy(3+) in Ge-Ga-S glass and its suitability for 1.3-microm fiber
      optical amplifier applications.
AB  - Absorption and emission spectra, along with lifetime measurements, of Dy(3+) in
      Ge-Ga-S glasses are reported. Fluorescence is observed at 1.3, 1.8, and 2.9
      microm. A Judd-Ofelt analysis is performed to determine branching ratios and
      quantum efficiencies. The hypersensitive transition (6)F(11/2) ? (6)H(15/2) at
      1.3 microm has a quantum efficiency of 17%. Its suitability for an optical
      amplifier at 1.3 microm depends on the excited-state absorption from the
      (6)H(11/2) and (6)H(13/2) states, which has not yet been measured.

PMID- 19844484
TI  - Holographic recording of complex images by double phase conjugation in
      Bi(12)TiO(20) fiberlike crystal.
AB  - Volume holographic recording of complex images with a double phase-conjugation
      mirror in a fiberlike Bi(12)TiO(20) single crystal, mutually pumped by two
      separate He-Ne lasers, is experimentally demonstrated. Complex images can be
      stored and reconstructed by use of even a partial input image. The advantages of
      the small-cross-section, light-confining photorefractive sample in comparison
      with bulk crystal are a wider spatial bandwidth of recorded images and the
      possibility of recording holograms by application of smaller ac voltages.

PMID- 19844485
TI  - Effect of applied fields on the Bragg condition and the diffraction efficiency in
      photorefractive crystals.
AB  - We explore theoretically and experimentally how application of an electric field
      to a photorefractive crystal affects the recording and the readout of holograms.
      We consider, for the first time to our knowledge, the effects of fringe bending
      caused by nonlinear two-wave mixing on the change in Bragg condition and
      diffraction efficiency as a function of the applied electric field. Practical
      performance limitations for holographic data storage and image amplification are
      discussed.

PMID- 19844486
TI  - Remote measurement of mode-coupling coefficients in birefringent fiber.
AB  - An optical scheme for a remote measurement of mode-coupling coefficients in
      birefringent fiber is proposed that uses wavelength scanning, white-light
      interferometry, and two phase-shifted channels for output spectrum detection. The
      procedure is outlined for two-channel signal processing. This technique can be
      used to develop distributed fiber-optic sensor for remote sensing. Its
      experimental verification is presented.

PMID- 19844487
TI  - Liquid-crystal point-diffraction interferometer.
AB  - A new point-diffraction interferometer has been developed with a liquid-crystal
      filter that permits arbitrary phase shifts to be introduced between the object
      and reference beams. A microsphere embedded within the liquid-crystal layer
      provides a locally generated reference beam. We phase shift the object beam by
      varying a voltage across the liquid crystals, thereby altering the refractive
      index of the birefringent nematic liquid crystals.

PMID- 19844488
TI  - Design of waveguide-grating filters with symmetrical line shapes and low
      sidebands.
AB  - We show that ideal reflection filters can be designed by combining guided-mode
      resonance effects in waveguide gratings with antireflection effects of thin-film
      structures. Since the guided-mode resonance effect overrides the antireflection
      effect this filter provides a symmetrical line shape with near-zero reflectivity
      over appreciable wavelength bands adjacent to the resonance wavelength. In the
      single-layer filter the same layer functions as the waveguide grating supporting
      the resonance and as the antireflection layer suppressing reflection around the
      resonance. A multilayer design allows the filter resonance peak to have a wide
      surrounding region of low reflectance. The central resonance wavelength, the
      filter linewidth, the range of the low sidebands, and the resonance line shape
      are all under the control of the designer.

PMID- 19844489
TI  - Low-noise optoelectronic photon number amplifier and quantum-optical tap:
      erratum.

PMID- 19844490
TI  - Second-harmonic and sum-frequency generation from optically trapped KTiOPO(4)
      microscopic particles by use of Nd:YAG and Ti:Al(2)O(3) lasers.
AB  - We describe the single-beam optical trapping of microscopic KTiQPO(4) crystals,
      using Nd:YAG and Ti:Al(2)O(3) lasers. The high power density of the laser beam at
      the crystals to be trapped induces the second-harmonic and sumfrequency
      generation. By changing the wavelength of the Ti:Al(2)O(3) laser, we detect the
      sum-frequency generation with the fixed wavelength of Nd:YAG laser between 430
      and 486 nm for the particle during the trapping.

PMID- 19844491
TI  - Optical trapping of metallic Rayleigh particles.
AB  - Metallic objects reflect light and have generally been considered poor candidates
      for optical traps, particularly with optical tweezers, which rely on a gradient
      force to provide trapping. We demonstrate that stable trapping can occur with
      optical tweezers when they are used with small metallic Rayleigh particles. In
      this size regime, the scattering pictures for metals and dielectrics are similar,
      and the larger polarizability of metals implies that trapping forces are greater.
      The latter fact makes the use of metal particles attractive for certain
      biological applications. Comparison of trapping forces for latex and gold spheres
      demonstrates that the gradient force is the major determinant of trapping
      strength and that competing effects, such as scattering or radiometric forces,
      are relatively minor.

PMID- 19844492
TI  - Pulsed-laser-induced dark traces in LiNbO(3):Zn and LiNbO(3):Mg.
AB  - Laser-induced dark traces in LiNbO(3):Zn (7.5 mol.%) and LiNbO(3):Mg (6.5 mol.%)
      crystals have been studied with the crystals as the component for 1064-532-nm
      second-harmonic generation of Nd:YAG radiation operating in a pulsed mode. The
      results show that, at high input power density, both crystals suffer from dark
      traces, which reduce the second-harmonic-generation efficiency. The dark traces
      are induced by the 532-nm radiation and can be recovered after the laser beam is
      shut off. The transmission loss spectra show a broad absorption peak near 400 nm.

PMID- 19844493
TI  - Efficient photoinduced second-harmonic generation in Ce-doped lead germanate
      glasses.
AB  - Efficient photoinduced second-harmonic generation in Ce-doped bulk lead germanate
      glasses is observed. A linear increase of photoinduced second-order nonlinearity
      with Ce concentration is obtained. The reported glasses can be encoded for
      frequency doubling with extremely low (as little as 30 W of peak power at 1.064
      microm) preparation intensities.

PMID- 19844494
TI  - Effect of cross-phase modulation on optical phase conjugation in dispersion
      shifted fiber.
AB  - The temporal effect of optical phase conjugation in dispersion-shifted fiber is
      studied numerically. Frequency chirping is induced in the conjugate pulse by the
      signal pulse and the pump wave through cross-phase modulation, which increases
      with the signal power and may distort the pulse shape when the conjugate pulse
      propagates in the standard fiber. It is also shown that, when the signal power is
      low, the optical phase conjugation is nearly ideal.

PMID- 19844495
TI  - High-order harmonic generation with an annular laser beam.
AB  - High-order harmonics have been generated by the use of an annular laser beam. The
      nonlinearity of harmonic production and the shorter wavelengths involved cause
      the harmonics to emerge strongly peaked on the laser axis. Thus the harmonics
      emerge from the focus inside the missing portion of the laser beam. This permits
      the laser to be blocked by an aperture that passes the harmonics.

PMID- 19844496
TI  - Interaction of self-guided beams of different frequencies.
AB  - We show that a self-guided beam in a nonlinear planar film can be split,
      switched, or deflected in a controlled manner by use of another self-guided beam
      of a different frequency. The new phenomena are power dependent and are
      potentially attractive for all-optical photonic device applications.

PMID- 19844497
TI  - Grating evolution in frequency-doubling fibers.
AB  - The position and the width of the chi((2)) grating in a frequency-doubling fiber
      were studied during the preparation process. The peak of the grating moves
      several centimeters from the input end to the output end of the fiber before the
      conversion efficiency saturates. On saturation, the grating moves toward the
      input end and becomes narrower.

PMID- 19844498
TI  - Reversible photodarkening and bleaching in Tb(3+)-doped optical fibers.
AB  - The darkening of Tb(3+)-doped phosphosilicate optical fibers by resonant
      excitation at 488 nm is found to be almost completely reversible by exposure to
      off-resonance excitation at 514 nm. The darkening and bleaching are three- and
      two-photon processes, respectively, and the steady-state absorption of the fiber
      is controllable by the competition between the two processes.

PMID- 19844499
TI  - 1.9-microm operation of a Tm:lead germanate glass waveguide laser.
AB  - We report what we believe to be the first planar-technology waveguide laser in
      the 2-microm region. Laser operation of the (3)H(4) to (3)H(6) transition of
      Tm(3+) ions in a lead germanate glass host has been observed in an ion-implanted
      planar waveguide.

PMID- 19844500
TI  - Single-mode 1.34-microm Nd:YVO(4) microchip laser with cw Ti:sapphire and diode
      laser pumping.
AB  - We report cw single-mode output at 1.34 microm in a Nd:YVO(4) microchip laser
      pumped separately with a Ti:sapphire laser and a diode laser in the region of 809
      nm. The 0.5 mm x 1.0 mm x 1.0 mm Nd(3+)-doped YVO(4) crystal produced output
      powers as high as 60 mW with slope efficiencies as high as 40% and laser
      thresholds between 155 and 275 mW by use of a pumped volume of approximately 150
      microm diameter and 0.5-mm length. Data are also presented for the laser's
      performance as a function of pump wavelength and for the spectral variation of
      the output with crystal temperature.

PMID- 19844501
TI  - Subpicosecond and continuous-wave laser operation of (F(2)(+))(H) and
      (F(2)(+))(AH) color-center lasers in the 2-microm range.
AB  - We report synchronously mode-locked subpicosecond and continuous-wave color
      center laser operation in the 1.8-2.4-microm wavelength range. For active
      materials we use (F(2)(+))(H) centers in KBr:O(2)(-) and (F(2)(+))(AH) centers in
      KBr:Na(+):O(2)(-) crystals. When the lasers are pumped with a continuous-wave or
      mode-locked NaCI (F(2)(+))(H)-center laser in a cascaded configuration, laser
      operation is obtained over the combined tuning range of 1.8-2.4 microm, with
      output powers as high as 150 mW. When synchronously mode locked with ~5-ps pump
      pulses, both KBr lasers yield typically ~1-ps pulse widths over the entire tuning
      range. Pulses as short as ~400 fs could be obtained at the expense of higher
      noise levels.

PMID- 19844502
TI  - Tunable optical parametric oscillators pumped by Ti:sapphire lasers.
AB  - We report on the application of tunable, pulsed Ti:sapphire lasers as efficient
      pump sources for optical parametric oscillators. Using a 90-deg phase-matched KTP
      crystal, we have generated output from 1030 to 1280 nm (signal) and 2180 to 3030
      nm (idler) by tuning the pump laser from 700 to 900 nm, with 49 mJ of combined
      signal and idler output energy at a pump level of 110 mJ. In addition, we have
      demonstrated degenerate optical parametric oscillator operation with a KNbO(3)
      crystal over the pump range of 720-818 nm and observed a 44% conversion
      efficiency.

PMID- 19844503
TI  - Propagation-induced adiabatic following in a semiconductor amplifier.
AB  - A propagation-induced transition from linear amplification into an adiabatic
      following regime is predicted for femtosecond pulses in an inverted semiconductor
      medium. This process is accompanied by considerable pulse shortening.

PMID- 19844504
TI  - Lasing characteristics of visible AlGaInP/AlGaAs vertical-cavity lasers.
AB  - We report the lasing characteristics of gain-guided AlGaInP/AlGaAs visible
      vertical-cavity surface-emitting laser diodes. At room temperature, continuous
      wave operation is achieved over the wavelength range of 657-685 nm with the
      minimum threshold current at 670 nm. Devices with a 10-microm diameter have
      threshold currents as low as 1.25 mA at room temperature (297 K) and 0.8 mA at
      250 K. In addition, a single predetermined linear polarization state is found,
      independent of the lasing mode order and operating temperature.

PMID- 19844505
TI  - Coherent effects in a self-mode-locked Ti:sapphire laser.
AB  - The spectral and temporal characteristics of approximately 10-fs pulses from a
      self-mode-locked Ti:sapphire laser were found to exhibit large deviations from
      the predictions of current theories of mode locking. A simple model that takes
      into account coherent coupling between the circulating pulse and the gain medium
      gives results in good agreement with experimental observations.

PMID- 19844506
TI  - Characteristics of a femtosecond transform-limited Kerr-lens mode-locked dye
      laser.
AB  - Using an SF6 glass plate as the intracavity Kerr medium and a double-prism pair
      for dispersion compensation, we developed a femtosecond transform-limited
      passively mode-locked dye laser. Self-starting mode locking is achieved with a
      dilute intracavity TCVEBI saturable-absorber jet. Within a 50% power drop the
      tuning range is 577-606 nm. Pulse characteristics of the laser agree with
      theoretical predictions based on the Ginzburg-Landau equation.

PMID- 19844507
TI  - Optimal filter approximation by means of a phase-only filter with quantization.
AB  - Approximate filters based on a phase-only filter for reliable recognition of
      objects are proposed. Good light efficiency and discrimination capability close
      to that of the optimal filter can be obtained. Computer simulation results are
      presented and discussed.

PMID- 19844508
TI  - Microscope imaging through highly scattering media.
AB  - Microscopic images of a test chart hidden behind a slab of a highly scattering
      medium were significantly improved by incorporation of a spatial filter located
      at the back Fourier-transform plane of the objective lens of a microscope. The
      image quality was shown to be improved further by detection of only the early
      arriving photons through time-resolved detection in combination with spatial
      filtering.

PMID- 19844509
TI  - Contribution of the 2(1)Ag state to the third-order optical nonlinearity in a
      squaraine dye.
AB  - We have measured the third-harmonic response, gamma, of a centrosymmetric
      squaraine dye (ISQ) in chloroform at a range of frequencies for which the third
      harmonic is above the strong, narrow peak in the dye's linear absorption spectrum
      but below the UV absorption band. By fitting the experimental dispersion of gamma
      using a four-level model, we determine the strength, location, and width of the
      lowest-lying two-photon transition. We find that the 2(1)Ag state appears just
      above the 1(1)Bu state in energy and that the 1(1)Bu-2(1)Ag transition moment is
      somewhat smaller than the transition moment between the ground state and the
      1(1)Bu state but much larger than previously predicted for comparable squaraine
      dyes.

PMID- 19844510
TI  - Electric-field-modulated photon echoes in Pr(3+):YAlO(3).
AB  - We measured the Stark coefficient for the (3)H(4)(1) ? (1)D(2)(1) transition of
      Pr(3+):YAlO(3), using the technique of Stark-modulated photon echoes. This gave a
      value of 58 kHz/(V cm(-1)) for the vector difference between ground-and excited
      state electric dipole moments. The resolution with which Stark shifts could be
      measured in these experiments was ~500 Hz, which is more than an order of
      magnitude less than the homogeneous linewidth.

PMID- 19844511
TI  - Thermalization effects between upper levels of green fluorescence in Er-doped
      silica fibers.
AB  - We present a spectroscopic study of the green fluorescence resulting from pump
      excited-state absorption in Er-doped silica fibers excited in the 800-nm range.
      The absorption and emission bands are selectively attributed to the (4)S(3/2) and
      (2)H(11/2) levels. The fluorescence response at two excitation wavelengths, the
      temperature behavior, and lifetime measurements demonstrate a fast thermalization
      between the (4)S(3/2) and (2)H(11/2) levels. This explains an important part of
      the (2)H(11/2) emission and the increase of the fluorescence intensity at high
      temperature.

PMID- 19844512
TI  - Method for holographic storage using peristrophic multiplexing.
AB  - A method of multiplexing holograms by rotating the material or, equivalently, the
      recording beams is described. Peristropic (Greek for rotation) multiplexing can
      be combined with other multiplexing methods to increase the storage density of
      holographic storage systems. Peristrophic multiplexing is experimentally
      demonstrated with Du Pont's HRF-150 photopolymer film. We multiplexed a total of
      295 holograms in a 38-microm-thick photopolymer film by combining peristrophic
      multiplexing with angle multiplexing.

PMID- 19844513
TI  - Dispersive interferometric profilometer.
AB  - The usual automated interferometric profilometers suffer from phase-unwrapping
      problems. We discuss a one-dimensional method for the absolute determination of
      the path difference in interferometers to obtain unique surface profiles with
      high accuracy.

PMID- 19844514
TI  - Imaging of reaction zones in hydrocarbon-air flames by use of planar laser
      induced fluorescence of CH.
AB  - A method for imaging the reaction zones in hydrocarbon-air flames is described.
      The technique is based on planar laser-induced fluorescence of the CH radical by
      use of excitation in the A(2)Delta ? X(2) II(1, 0) band and broadband detection
      from the overlapping (1, 1) and (0, 0) bands. This strategy is found to provide a
      significant improvement in image quality compared with that from previously
      employed CH imaging techniques. Results are presented for propane-air flames, and
      a comparison of possible imaging strategies is given.

PMID- 19844515
TI  - 120 x 100 pixel antiblooming array based on optically addressed ferroelectric
      liquid-crystal cells.
AB  - We describe the principle and the operation of a 120 x 100 pixel antiblooming
      array. Each cell in the array is made up of a hydrogenated amorphous silicon
      photoconductor layer driving a ferroelectric liquid-crystal shutter. The device
      is designed to be coupled with a CCD camera to prevent high-blooming overload and
      image lag.

PMID- 19844516
TI  - Mo/Y multilayer mirrors for the 8-12-nm wavelength region.
AB  - Mo/Y multilayer mirrors were deposited by dc magnetron sputtering under different
      deposition conditions. They were characterized by reflectance measurements at
      normal and grazing angles of incidence, by transmission electron microscopy, and
      by Auger depth profiling. Normal-incidence peak reflectances of 34% and 22% were
      measured at wavelengths of 11.5 and 8.1 nm, respectively. Interface roughness and
      contamination of the layers during deposition limit the peak reflectance of these
      Mo/Y mirrors.

PMID- 19844517
TI  - Three-terminal adaptive nematic liquid-crystal lens device.
AB  - A 1 mm x 1 mm nematic liquid-crystal three-terminal device for optical beam
      forming (focusing/spoiling) is fabricated. A thin-film-resistor network on the
      device substrate layer is used to control the voltages on the 98 internal lens
      electrodes by use of only one variable external driver. By using a high
      resistance thin-film layer of amorphous silicon under the 98-element parallel
      electrode structure layer, we generate a near-continuous index perturbation to
      form a cylindrical lens. The focal length of this lens is continuously variable
      from inifinity to 12 cm by use of a variable 1-4-V-peak 1-kHz square-wave
      external terminal control signal.

PMID- 19844518
TI  - Resonant cascaded surface-emitting second-harmonic generation: a strong third
      order nonlinear process.
AB  - A novel practical scheme for implementation of the cascaded nonlinearity with
      surface-emitting second-harmonic generation in the Fabry-Perot cavity is
      presented. We show that such a scheme can be efficiently used for optical
      limiting and optical phase conjugation at a pump power of lessthan 100 mW.

PMID- 19844519
TI  - Adiabatic amplification of solitons by means of nonlinear amplifying loop
      mirrors.
AB  - We study the transmission properties of a nonlinear amplifying loop mirror that
      acts as an adiabatic amplifier of solitons. The adiabatic nature of the operation
      is quantified by evaluation of the energy and the Hamiltonian of dispersive-wave
      components contained in the output pulse. Near-adiabatic amplification is
      possible, and a chirp-free solition can be generated with an amplification ratio
      (compression ratio) of ~2 by a proper design of the device.

PMID- 19844520
TI  - Efficient intracavity sum-frequency generation of 490-nm radiation by use of
      potassium niobate.
AB  - Efficient sum-frequency generation of 910-nm radiation from a Ti:A1(2)O(3) laser
      and the circulating 1064-nm light inside a diode-pumped Nd:YVO(4) laser cavity
      has been achieved by use of b-axis KNbO(3). Blue-green output of 20 mW was
      generated with 100 mW of mixing power (910 nm) and a Nd:YVO(4) laser pumped by a
      400-mW laser diode.

PMID- 19844521
TI  - Creation of second-order nonlinearity in polymers by light-induced asymmetric
      charge injection.
AB  - A new method for creating and enhancing second-order optical nonlinearity in
      polymer-dye films by asymmetric photoinjection of electric charges is introduced.
      The samples are composed of two separate layers, an organic photoconductor that
      generates the electric charges and a hyperpolarizable organic film that traps
      them. The nonlinearity caused by asymmetric charge injection does not arise from
      dipolar alignment; consequently, it can be observed either in the absence of, or
      to enhance, the conventional dipolar alignment nonlinearity.

PMID- 19844522
TI  - Design of fiber gratings for total dispersion compensation.
AB  - An optical fiber grating has theoretically been designed that would be capable of
      compressing a dispersionbroadened pulse of 100 ps down to the transform limit of
      20 ps, with a total reflectance of ~75%. A numerical recipe is presented for the
      design of a fiber grating, whose spectral response closely follows an arbitrarily
      chosen profile, both for the reflectance and the phase factor. The resulting
      grating consists of a number of subgratings, all of which have the same grating
      period but a different spatial phase and coupling coefficient.

PMID- 19844523
TI  - Bending loss of leaky modes in optical fibers with arbitrary index profiles.
AB  - Two new bending loss theories for leaky modes in optical fibers with arbitrary
      refractive-index profiles are presented. The numerical results are compared with
      the two known theories of Marcuse and Shah and of Vassalo. The two new theories
      are valid in a larger region of bend radii than the Marcuse-Shah theory. For the
      first time, to the author's knowledge, it is shown that for even and odd modes
      the bending loss is different, in general.

PMID- 19844524
TI  - Hollow glass waveguides for broadband infrared transmission.
AB  - Broadband hollow glass waveguides have been fabricated with losses as low as 0.15
      dB/m at 10.6 microm. We make these hollow glass waveguides by coating the inside
      of polyimide-coated silica-glass tubing with a metallic layer followed by a thin
      dielectric coating of a metal halide. The bore sizes of the guides range from 320
      to 700 microm, and we have made lengths as long as 3 m. The bending radii of the
      waveguides are less than 5 cm for bore sizes less than 500 microm. We have used
      these waveguides to deliver greater than 80 W of CO(2) laser power and 5 W of
      Er:YAG laser power. The hollow glass guides are inexpensive, robust, and quite
      flexible and therefore a good infrared fiber for power and sensor applications.

PMID- 19844526
TI  - Self-starting Kerr-lens mode locking of a Ti:sapphire laser.
AB  - It is shown that Kerr-lens mode locking of a Ti:sapphire laser, with no
      intracavity elements except the laser rod and the dispersion-compensating prisms,
      can be made to be completely self-starting. We achieve this result by carefully
      designing the resonator to maximize the nonlinear mode variations and dynamic
      loss modulation.

PMID- 19844525
TI  - Blue-light generation by frequency doubling of an 810-nm cw GaAlAs diode laser in
      a quasi-phase-matched LiNbO(3) crystal.
AB  - A third-order quasi-phase-matched LiNbO(3) crystal was used to double the output
      of an 810-nm cw GaAlAs diode laser directly. A blue-light output power of 0.35 mW
      was measured with a conversion efficiency of 0.13%.

PMID- 19844527
TI  - Hybrid diode-laser fiber-amplifier source of high-energy ultrashort pulses.
AB  - We demonstrate what we believe is the first compact laser system for generating
      ultrashort microjoule-energy optical pulses. Linearly chirped pulses from
      monolithic tunable Bragg-reflection laser diodes were amplified in a diode-pumped
      two-stage erbium-doped fiber amplifier and compressed with a grating-pair
      compressor. The laser diodes had their emission wavelengths at 1.538 and 1.562
      microm. The highest pulse energies obtained were 2 microJ at the repetition
      frequencies of 1-10 kHz and were at the saturation energy level of the fiber
      amplifier. The shortest duration of compressed pulses is 1.8 ps.

PMID- 19844528
TI  - Continuous-wave total-internal-reflection optical parametric oscillator pumped at
      1064 nm.
AB  - We report what is to our knowledge the first cw 1064-nm-pumped optical parametric
      oscillator (OPO), using a critically phase-matched (theta(pm) = 45.5 degrees ),
      monolithic total-internal-reflection, doubly resonant OPO fabricated from
      congruent LiNbO(3). Frustrated total-internal-reflection provides variable output
      coupling for the signal and the idler. The measured finesse of 6000 at 2014 nm
      implies a round-trip power loss of 0.1%. The low round-trip power losses
      compensate the 2 degrees Poynting vector walk-off and give a threshold of 130 mW.
      A passive thermal feedback mechanism causes the OPO to oscillate stably in a
      single axial-mode pair for more than 30 min. The OPO output tunes in 0.1-nm steps
      from 2040 to 2225 nm by tuning the pump frequency.

PMID- 19844530
TI  - Phase-conjugated XeCl laser resonator.
AB  - Self-Q switching of a XeCl laser fitted with a resonator containing a stimulated
      Brillouin-scattering phase-conjugate reflector is demonstrated. Q-switched laser
      pulses of 0.2-mJ energy and 2.5-ns duration and with a divergence close to the
      diffraction limit were obtained. A spectral narrowing of the two strong lines at
      307.98 and at 308.19 nm exhibited by the XeCl laser spectrum was also observed.

PMID- 19844529
TI  - Raman-shifted KrF laser radiation with low amplified spontaneous emission for a
      rotational Raman daytime-temperature lidar.
AB  - Various configurations of a tunable two-stage KrF laser have been investigated
      for providing powerful laser pulses with very low amplified spontaneous emission
      (ASE). The lowest fraction (0.00017%) of ASE was attained with a single-pass
      amplifier and a phase-conjugate Brillouin mirror. The most suitable application
      envisaged for the laser source, i.e., remote daytime-temperature measurement by
      means of rotational Raman scattering, is a dedicated oscillator-amplifier
      configuration with an ASE of 0.005% at an output of 300 mJ. The very low values
      of ASE were measured with the aid of a thallium atomic-vapor filter.

PMID- 19844531
TI  - Efficient continuous-wave TEM(00) operation of a transversely diode-pumped Nd:YAG
      laser.
AB  - A new, highly efficient, scalable technique for cw high-power diode-array side
      pumping of gain media has been eveloped. The use of simple all-reflective optics
      permits diode emission collection efficiencies of >95%. We have achieved a cw
      TEM(00) mode output (M(2) < 1.1) of 13.1 W at 1.06 microm from a Nd:YAG rod
      pumped with 60 W of laser-diode output (808 nm), representing 22% conversion
      efficiency (29% conversion of absorbed pump power). Numerical simulations and
      experimental results indicate that good thermal management results in thermally
      induced aberrations of <lambda/8 across the rod.

PMID- 19844532
TI  - Cross-locking dynamics in a two-color mode-locked Ti:sapphire laser.
AB  - We investigate the nonlinear interactions between pulses of two different
      wavelengths within a single cross-mode-locked femtosecond Ti:sapphire laser. We
      show that the nonlinear interaction caused by self-focusing can correct for a
      difference in cavity lengths of as much as +/-3 microm, corresponding to 20% of
      the pulse width on each round trip. Further, we show that the concept of mean
      group delay can be extended to a pair of pulses with disparate spectra and
      spatial distribution in a nonlinear regenerative system.

PMID- 19844533
TI  - Single-shot measurement of the intensity and phase of a femtosecond UV laser
      pulse with frequency-resolved optical gating.
AB  - We extend to the ultraviolet frequency-resolved optical gating a new method for
      measuring the intensity and phase evolution of an individual ultrashort pulse
      without assumption. Using frequency-resolved optical gating, we measure a 310-fs,
      308-nm pulse, whose phase is approximately cubic in time. We show that this phase
      distortion probably results from self-phase modulation and amplifier detuning.

PMID- 19844534
TI  - Ultrafast pulse propagation in periodic optical media: a generalized finite
      difference time-domain approach.
AB  - A generalized finite-difference time-domain method is used to model the
      propagation of ultrafast optical pulses through periodic structures with a
      frequency-dependent material response. Excellent agreement with a thin multilayer
      decomposition is found for the cases of dispersive and nondispersive optical
      media.

PMID- 19844535
TI  - Optoelectronic implementation of a fuzzy winner-take-all network for fuzzy logic
      inference.
AB  - A fuzzy winner-take-all model is proposed for performing fuzzy logic inference.
      An optoelectronic scheme for this model is presented, and experimental results
      are given.

PMID- 19844536
TI  - Enhancement of the signal-to-background ratio in photorefractive two-wave mixing
      by mutually incoherent two-beam coupling.
AB  - We present and experimentally demonstrate a new method for enhancing the signal
      to-background ratio of two-wave mixing in photorefractive crystals. The method
      uses a mutually incoherent third beam to suppress the fanning in a dark ring
      shaped region in which the amplified signal is located. A 20-fold improvement of
      the signal-to-background ratio is measured in BaTiO(3) at lambda = 514 nm. The
      extension of this principle to wide-field-of-view heterodyne detection is
      discussed.

PMID- 19844537
TI  - Effects of a random phase screen on the performance of an imaging system.
AB  - The effect of a random phase screen on the performance of an imaging system is
      described. Analytical expressions of the average image spectrum are developed for
      both coherent and incoherent radiation. It is shown that the random-phase-induced
      ansioplanatism can give rise to the characteristics of superresolution. The
      conditions of superresolution are derived, and the relationship among various
      parameters for the occurrence of superresolution is discussed.

PMID- 19844538
TI  - Optically programmable two-channel sorting network based on a polarization- and
      area-encoded technique.
AB  - We describe an optical cascadable polarization- and area-encoded sorting system
      that is capable of independently sorting two arrays of unipolar data, each in an
      arbitrary order specified by a corresponding instruction. The sorting
      instructions can be easily programmed by external optical signals. The system can
      be used for sorting a single array of bipolar data.

PMID- 19844539
TI  - Recall of linear combinations of stored data pages based on phase-code
      multiplexing in volume holography.
AB  - We describe a novel method for the recall of linear combinations of stored data
      pages in a volume holographic memory based on phase-code multiplexing. Recall is
      demonstrated by use of a compound phase-and-amplitude spatial light modulator in
      the reference beam path.

PMID- 19844540
TI  - Effect of coherence of the source on the images obtained with a photon scanning
      tunneling microscope.
AB  - The photon scanning tunneling microscope is based on the frustration of a total
      internal reflection beam by the end of an optical fiber. This microscope has been
      used to obtain topographic information generally on smooth samples. We compare
      images obtained with different sources, such as He-Ne and He-Cd lasers and white
      light sources, and show the role of the coherence of the source on the formation
      of the images.

PMID- 19844541
TI  - Active silica-gel films for hydrogen sulfide optical sensor application.
AB  - We have developed a novel H(2)S-sensitive film by immobilizing thionine in a
      silica matrix by means of the solgel process. The film is stable, reversible, and
      sensitive to dissolved H(2)S to as low as parts-per-billion levels. The
      photochemical instability of thionine in basic solution has been improved
      dramatically by use of this immobilization technique and silica substrate. Based
      on the developed new films, sensors for monitoring H(2)S may be prepared either
      by a fiber-optic approach or by integrated optical circuit techniques.

PMID- 19844542
TI  - Refractive-index measurement at high spatial resolution by source doubling.
AB  - We report a new interferometric technique for measuring the refractive index of a
      thin solid sample at submillimetric resolution. Source doubling is obtained with
      a modified triangular common path arrangementused to generate a spatially
      distributed interferogram detected by a CCD line sensor. When inserted into
      theoptical path, the sample alters the distance between the two secondary point
      sources, thereby changing the fringe spacing. We determined the refractive index
      at 632.8 nm by measuring the change. The spatial resolution of the measurement is
      limited by the size of the primary source and the magnification of the probe spot
      forming lens. The technique is employed to determine the refractive index of a
      microscope slide with 150-microm probe spots.

PMID- 19844543
TI  - Dual diode-laser fiber-optic diagnostic for water-vapor measurements.
AB  - We present a novel diode-laser diagnostic for water-vapor measurements based on
      absorption spectroscopy. Two InGaAsP diode lasers were used to record H(2)O
      absorption line shapes near 1395 nm at a 3-kHz repetition rate along a single
      path through a water-vapor flow field generated in a shock tube. The use of two
      lasers permits simultaneous line-shape measurements in different spectral regions
      and facilitates the selection of appropriate line pairs for thermometry. The
      wavelength tuning rate was determined by use of a fiber-optic device known as a
      ring interferometer. Flow-field conditions (1320 K, 0.3 atm) inferred from
      measured line shapes compared favorably with calculated values.

PMID- 19844544
TI  - Analysis of techniques for autocorrelation estimates from clipped data.
AB  - We analyze a series of techniques for obtaining estimates of the autocorrelation
      function that canbe applied to clipped data. The direct autocorrelation of
      clipped data is the simplest technique and provides results that are the same as
      or better than those from other methods. It is also shownthat it is not possible
      to obtain the theoretical autocorrelation function of the signal when clipped
      data are used.

PMID- 19844545
TI  - Single-mode propagation of mutual temporal coherence: equivalence of time and
      frequency measurements of polarization-mode dispersion.
AB  - A formalism is presented for treatment of the mutual temporal coherence between
      orthogonal polarization modes in single-mode optical systems, permitting
      calculation of the effect of propagation through birefringent devices on this
      coherence. We demonstrate that, allowing for differences similar to the
      birefringent effects of fiber pigtails, polarization-mode dispersion data
      measured by use of frequency-scanning techniques are related by the Fourier
      transform to data measured by use of interferometric techniques.

PMID- 19844546
TI  - Dispersion compensation in coherence-domain multiplexed systems.
AB  - An ultrahigh-bandwidth point-to-point communications system based on white-light
      sources, pulse shapers, and interferometric receivers is proposed. Dispersion
      compensation by interferometric receivers is described and demonstrated. Linear
      dispersion-limited communications bandwidths are shown to scale with the square
      root of the data packet length.

PMID- 19844547
TI  - Determination of resonant and nonresonant third-order nonlinearities of organic
      molecules by phase-conjugate interferometry.
AB  - We have used a phase-conjugate interferometer to determine the real and imaginary
      parts of the third-order hyperpolarizability of 3,3'-diethyloxadicarbocyanine
      iodide (DODCI) and 4-methoxy-4'-nitrostilbene (MONS) at 1064 nm. For DODCI the
      values are enhanced by a two-photon resonance, and the two-photon extinction
      coefficient is determined. However, the nonlinear loss of DODCI is dominated by
      linear absorption from the two-photon excited state. We could not observe linear
      or nonlinear absorption for the MONS solutions, and we have determined the
      nonresonant third-order hyperpolarizability for this molecule.

PMID- 19844548
TI  - Measurement of free-carrier nonlinearities in ZnSe based on the Z-scan technique
      with a nanosecond laser.
AB  - Self-defocusing and nonlinear absorption resulting from two-photon-excited free
      charge carriers were observed in polycrystalline ZnSe at the low power density of
      ~ 30 MW/cm(2) by use of the Z-scan technique with nanosecond laser pulses. The
      total carrier absorption cross section and the variation of refractive index per
      unit of photoexcited carrier density were estimated to be 0.80 +/- 0.10 x 10(-18)
      cm(2) and 0.60 +/- 0.15 x 10(-21) cm(3), respectively.

PMID- 19844549
TI  - Spatial distribution of 650-nm luminescence in UV-processed germanosilicate
      preforms.
AB  - Broadband luminescence at ~650 nm obtained on excitation at 633 and 647.5 nm is
      shown to be markedly increased in a UV-processed germanosilicate preform. The
      luminescence profile across the core is found to follow that of the germanium
      concentration.

PMID- 19844550
TI  - Four-photon-mixing-mediated stimulated Raman scattering in a multimode optical
      fiber.
AB  - Stimulated Raman scattering with 532-nm pulsed laser light is investigated in a
      7.9-microm-core step-index multimode fiber. While low-intensity pump or single
      mode LP(01) excitation produces the usual stimulated Raman scattering light,
      mixed-mode (LP(01) + LP(02)) excitation with pump intensities of ~5 kW uniformly
      shifts the multiorder Stokes Raman spectrum by an amount determined by fiber
      parameters, thus making stimulated Raman scattering tunable. This is due to the
      mediating influence of the four-photon mixing in the fiber.

PMID- 19844551
TI  - Organic-inorganic optical materials.
AB  - We describe the use of an intriguing class of materials, termed polycerams, for
      applications in integrated optics. Polycerams are ceramic-polymer hybrid
      materials that are synthesized by wet-chemical methods. As films they can be
      deposited in single-step operations with thicknesses from <100 nm to >5 microm,
      and their refractive indices and Abbe numbers can be varied over a wide range.
      Polycerams synthesized as planar waveguides exhibit optical attenuations as low
      as <0.15 dB/cm, and they can be patterned by embossing. These materials exhibit
      exceptional optical properties that are due to combination of organic and
      inorganic constituents at the molecular level.

PMID- 19844552
TI  - Improved two-dimensional beam-propagation method for three-dimensional integrated
      optical waveguide structures having rectangular-core cross sections.
AB  - An optimized effective index method is combined with a two-dimensional beam
      propagation method to form an efficient design tool for integrated-optical
      waveguide structures with rectangular-core cross sections. The accuracy is
      evaluated by comparisons with the results from a full three-dimensional beam
      propagation method.

PMID- 19844553
TI  - Broadband superfluorescent emission of the (3)H(4) ? (3)H(6) transition in a Tm
      doped multicomponent silicate fiber.
AB  - We report the observation of amplified spontaneous emission in the (3)H(4) ?
      (3)H(6) transition of Tm(+3) in a Ta(2)O(5)-doped multicomponent silicate fiber.
      The evolutions of the spectral shape, output power, and center wavelength were
      measured as a function of fiber length and pump power in the previously unstudied
      high-power range, where saturation effects dominate. An output power of 1 mW has
      been achieved at 1.91 microm with a bandwidth of 77 nm.

PMID- 19844554
TI  - Self-optimized resonator for optical pumping of solid-state lasers.
AB  - We show that the proper use of a self-imaging confocal cavity can be a simple way
      to optimize the efficiency of optical pumping of solid-state lasers. In this type
      of resonator the transverse mode self-adjusts to fit the pumped volume optimally.
      Self-optimization of the mode size of a laser-diode pump Nd:YAG laser (54% slope
      efficiency) is demonstrated, and an intrinsic efficiency of 68% is measured.

PMID- 19844555
TI  - Use of the prepulse technique to enhance the weak 18.2-nm laser line in neonlike
      selenium.
AB  - We report strong lasing in selenium on the neonlike 3p ? 3s, J = 0 ? 1 transition
      at 18.2 mn when the prepulse technique of using a low-intensity prepulse before
      the main optical drive pulse is used to illuminate the selenium target. Without
      the use of the prepulse, this line is 2 orders of magnitude weaker. The usual J =
      2 ? 1 lines at 20.6 and 20.9 nm are observed to dominate the spectra both with
      and without the use of the prepulse. These experiments may provide important
      clues to help our understanding of why the 18.2-nm line, which was predicted to
      dominate the laser output, was always observed weakly in previous experiments.

PMID- 19844557
TI  - 3-microm cw laser operations in erbium-doped YSGG, GGG, and YAG.
AB  - We have demonstrated cw laser operation at wavelengths near 3 microm from
      monolithic, Er-doped YSGG, GGG, and YAG lasers by direct upper-state pumping in
      the 0.97-microm wavelength region with either a Ti:sapphire laser or InGaAs diode
      lasers. We have obtained slope efficiencies as high as 31% and, with diode-laser
      pumping, output powers of 0.5 W. In addition, we have demonstrated tunable single
      frequency operations from Er:YAG.

PMID- 19844556
TI  - In situ small-signal gain of solid-state lasers determined from relaxation
      oscillation frequency measurements.
AB  - We present a simple, in situ technique to calculate the small-signal gain of
      typical solid-state continuous-wave lasers, such as Nd:YAG and Nd:YLF lasers, by
      measuring the frequency of the relaxation oscillation noise peak. The laser's
      small-signal gain can be directly calculated from the frequency of the relaxation
      oscillation with knowledge of the upper-state lifetime, the cavity round-trip
      time, and total losses, which are typically well-known values. When the laser is
      pumped many times above threshold the losses do not need to be known accurately.
      This technique is compared with the traditional method of changing output
      couplers to establish its accuracy.

PMID- 19844558
TI  - Ultraviolet ultrafast pump-probe laser based on a Ti:sapphire laser system.
AB  - An ultrafast spectroscopic pump-probe apparatus for detection of ultraviolet time
      resolved spectra is described. Frequency doubling of an 810-nm 0.3-TW Ti:sapphire
      laser system yields 15-mJ 165-fs pulses at 405 nm. We obtain pulse energies of
      0.8 mJ by frequency tripling to 270 nm. An ultraviolet supercontinuum extending
      from 200 to 600 nm is also generated in water by use of the frequency-doubled 405
      nm light. The system operates at a 5-Hz repetition rate and is useful for
      applications in deep-ultraviolet pump-probe subpicosecond spectroscopy.

PMID- 19844559
TI  - Pulse evolution in a broad-bandwidth Ti:sapphire laser.
AB  - We demonstrate that by operating near the zero second- and third-order dispersion
      point in a self-mode-locked Ti:sapphire laser we can generate sub-10-fs pulses.
      Our numerical simulations show that the pulse duration is limited by fourth-order
      dispersion and that shorter pulses will be possible if this can be reduced. Also,
      by inserting a pellicle in various positions in a Ti:sapphire cavity, we have
      measured the intracavity pulse duration and chirp of the circulating pulse in the
      laser. Our results demonstrate that the pulse is shortest near the middle of the
      laser crystal, in one direction of propagation. In the other direction of
      propagation, the pulse is positively chirped and several times longer.

PMID- 19844560
TI  - Uniqueness and sampling conditions for image reconstruction from the Hartley
      transform intensity.
AB  - Using a constructive proof, I show that a real two-dimensional image is uniquely
      determined by theintensity of its Hartley transform if the latter is sampled on a
      particular set of points whose density is approximately half the Nyquist density
      for the intensity. This result indicates that image reconstruction from the
      Hartleytransform intensity is in general overdetermined and sub-Nyquist sampled.

PMID- 19844561
TI  - Terahertz spectroscopy of three-dimensional photonic band-gap crystals.
AB  - We have fabricated and built three-dimensional photonic band-gap crystals with
      band-gap frequencies larger than 500 GHz. We built the crystals by stacking
      micromachined (110) silicon wafers. The transmission and dispersion
      characteristics of the structures were measured by an all-electronic terahertz
      spectroscopy setup. The experimental results were in good agreement with
      theoretical calculations. To our knowledge, our new crystal has the highest
      reported photonic band-gap frequency.

PMID- 19844562
TI  - High-aperture raster holography for particle imaging.
AB  - A novel approach to in-line particle holography is described, and its superiority
      is experimentally demonstrated. During recording, a raster diffuser is used to
      increase the effective angular aperture of particle scattering, and a raster
      screen is placed in front of hologram to mask the unscattered diffuse light. In
      reconstruction, a new type of spatial filter passes only the spherical waves from
      the interrogation region, effectively blocking the reconstruction beam,
      separating the real and virtual images, and suppressing the strong forward
      scattering. This new scheme provides particle images with higher contrast,
      reduced speckle noise, and a smaller depth of focus than conventional in-line
      holography.

PMID- 19844563
TI  - Phase stepping in fiber-based speckle shearing interferometry.
AB  - An optical-fiber-based speckle shearing interferometer for an out-of-plane
      displacement derivative measurement is described. The technique uses a highly
      birefringent optical fiber to illuminate a test object with equal amounts of
      orthogonally polarized light, and the interferometer is readily phase stepped,
      without mechanical movement of components, by strain modulation of the relative
      phase of the polarization states in the fiber. A Wollaston prism is used to
      produce two sheared images with adjustable shear.

PMID- 19844564
TI  - Theoretical analysis of a distributed polarimetric sensor with birefringent
      optical fibers in noncoherent light.
AB  - We have studied the influence of the angular rotations among four birefringent
      optical fibers on the performance of a system of intrinsic sensors in noncoherent
      light. The results obtained by the Jones formalism show that angular rotations of
      the order of 5 degrees are sufficient to yield the visibility required for
      detection of the parameters of interest. As the angular rotations come closer to
      1 degrees , which is experimentally more difficult, the signal has better
      contrast.

PMID- 19844565
TI  - Fiber-optic evanescent wave sensor for gas detection.
AB  - A novel fiber-optic evanescent wave sensor is presented. The sensor, composed of
      a lead salt tunable infrared laser and a multimode uncladded silver halide
      infrared optic fiber, was used for rapid measurement of sulfur hexafluoride
      pressures at a few-percent detection limit. High-precision detection and
      identification of a large variety of gases are possible.

PMID- 19844566
TI  - Liquid-crystal prisms for tip-tilt adaptive optics.
AB  - Results from an electrically addressed liquid-crystal cell producing continuous
      phase profiles are presented. The adaptive deflection of a beam of light for use
      in a tip-tilt adaptive optics system is demonstrated. We compare the optical
      performance of liquid-crystal prisms with experimental data on atmospheric seeing
      at the William Herschel Telescope.

PMID- 19844567
TI  - Mo/Y multilayer mirrors for the 8-12-nm wavelength region.
AB  - Mo/Y multilayer mirrors were deposited by dc magnetron sputtering under different
      deposition conditions. They were characterized by reflectance measurements at
      normal and grazing angles of incidence, by transmission electron microscopy, and
      by Auger depth profiling. Normal-incidence peak reflectances of 34% and 22% were
      measured at wavelengths of 11.5 and 8.1 nm, respectively. Interface roughness and
      contamination of the layers during deposition limit the peak reflectance of these
      Mo/Y mirrors.

PMID- 19844568
TI  - Oldest evidence of tool making hominins in a grassland-dominated ecosystem.
AB  - BACKGROUND: Major biological and cultural innovations in late Pliocene hominin
      evolution are frequently linked to the spread or fluctuating presence of C(4)
      grass in African ecosystems. Whereas the deep sea record of global climatic
      change provides indirect evidence for an increase in C(4) vegetation with a shift
      towards a cooler, drier and more variable global climatic regime beginning
      approximately 3 million years ago (Ma), evidence for grassland-dominated
      ecosystems in continental Africa and hominin activities within such ecosystems
      have been lacking. METHODOLOGY/PRINCIPAL FINDINGS: We report stable isotopic
      analyses of pedogenic carbonates and ungulate enamel, as well as faunal data from
      approximately 2.0 Ma archeological occurrences at Kanjera South, Kenya. These
      document repeated hominin activities within a grassland-dominated ecosystem.
      CONCLUSIONS/SIGNIFICANCE: These data demonstrate what hitherto had been
      speculated based on indirect evidence: that grassland-dominated ecosystems did in
      fact exist during the Plio-Pleistocene, and that early Homo was active in open
      settings. Comparison with other Oldowan occurrences indicates that by 2.0 Ma
      hominins, almost certainly of the genus Homo, used a broad spectrum of habitats
      in East Africa, from open grassland to riparian forest. This strongly contrasts
      with the habitat usage of Australopithecus, and may signal an important shift in
      hominin landscape usage.

PMID- 19844569
TI  - Evidence for repeated independent evolution of migration in the largest family of
      bats.
AB  - BACKGROUND: How migration evolved represents one of the most poignant questions
      in evolutionary biology. While studies on the evolution of migration in birds are
      well represented in the literature, migration in bats has received relatively
      little attention. Yet, more than 30 species of bats are known to migrate annually
      from breeding to non-breeding locations. Our study is the first to test
      hypotheses on the evolutionary history of migration in bats using a phylogenetic
      framework. METHODS AND PRINCIPAL FINDINGS: In addition to providing a review of
      bat migration in relation to existing hypotheses on the evolution of migration in
      birds, we use a previously published supertree to formulate and test hypotheses
      on the evolutionary history of migration in bats. Our results suggest that
      migration in bats has evolved independently in several lineages potentially as
      the need arises to track resources (food, roosting site) but not through a series
      of steps from short- to long-distance migrants, as has been suggested for birds.
      Moreover, our analyses do not indicate that migration is an ancestral state but
      has relatively recently evolved in bats. Our results also show that migration is
      significantly less likely to evolve in cave roosting bats than in tree roosting
      species. CONCLUSIONS AND SIGNIFICANCE: This is the first study to provide
      evidence that migration has evolved independently in bat lineages that are not
      closely related. If migration evolved as a need to track seasonal resources or
      seek adequate roosting sites, climate change may have a pivotal impact on bat
      migratory habits. Our study provides a strong framework for future research on
      the evolution of migration in chiropterans.

PMID- 19844570
TI  - The influence of bacterial diet on fat storage in C. elegans.
AB  - BACKGROUND: The nematode Caenorhabditis elegans has emerged as an important model
      for studies of the regulation of fat storage. C. elegans feed on bacteria, and
      various strains of E. coli are commonly used in research settings. However, it is
      not known whether particular bacterial diets affect fat storage and metabolism.
      METHODOLOGY/PRINCIPAL FINDINGS: Fat staining of fixed nematodes, as well as
      biochemical analysis of lipid classes, revealed considerable differences in fat
      stores in C. elegans growing on four different E. coli strains. Fatty acid
      composition and carbohydrate levels differ in the E. coli strains examined in
      these studies, however these nutrient differences did not appear to have a
      causative effect on fat storage levels in worms. Analysis of C. elegans strains
      carrying mutations disrupting neuroendocrine and other fat-regulatory pathways
      demonstrated that the intensity of Nile Red staining of live worms does not
      correlate well with biochemical methods of fat quantification. Several
      neuroendocrine pathway mutants and eating defective mutants show higher or lower
      fat storage levels than wild type, however, these mutants still show differences
      in fat stores when grown on different bacterial strains. Of all the mutants
      tested, only pept-1 mutants, which lack a functional intestinal peptide
      transporter, fail to show differential fat stores. Furthermore, fatty acid
      analysis of triacylglycerol stores reveals an inverse correlation between total
      fat stores and the levels of 15-methylpalmitic acid, derived from leucine
      catabolism. CONCLUSIONS: These studies demonstrate that nutritional cues
      perceived in the intestine regulate fat storage levels independently of
      neuroendocrine cues. The involvement of peptide transport and the accumulation of
      a fatty acid product derived from an amino acid suggest that specific peptides or
      amino acids may provide nutritional signals regulating fat metabolism and fat
      storage levels.

PMID- 19844571
TI  - Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by
      BDNF, are associated with memory and general cognitive abilities.
AB  - BACKGROUND: Human memory and general cognitive abilities are complex functions of
      high heritability and wide variability in the population. The brain-derived
      neurotrophic factor (BDNF) plays an important role in mammalian memory formation.
      METHODOLOGY / PRINCIPAL FINDING: Based on the identification of genes markedly up
      regulated during BDNF-induced synaptic consolidation in the hippocampus, we
      selected genetic variants that were tested in three independent samples, from
      Norway and Scotland, of adult individuals examined for cognitive abilities. In
      all samples, we show that markers in the doublecortin- and calmodulin kinase like
      1 (DCLK1) gene, are significantly associated with general cognition (IQ scores)
      and verbal memory function, resisting multiple testing. DCLK1 is a complex gene
      with multiple transcripts which vary in expression and function. We show that the
      short variants are all up-regulated after BDNF treatment in the rat hippocampus,
      and that they are expressed in the adult human brain (mostly in cortices and
      hippocampus). We demonstrate that several of the associated variants are located
      in potential alternative promoter- and cis-regulatory elements of the gene and
      that they affect BDNF-mediated expression of short DCLK1 transcripts in a
      reporter system. CONCLUSION: These data present DCLK1 as a functionally pertinent
      gene involved in human memory and cognitive functions.

PMID- 19844572
TI  - DYRK1A, a novel determinant of the methionine-homocysteine cycle in different
      mouse models overexpressing this Down-syndrome-associated kinase.
AB  - BACKGROUND: Hyperhomocysteinemia, characterized by increased plasma homocysteine
      level, is associated with an increased risk of atherosclerosis. On the contrary,
      patients with Down syndrome appear to be protected from the development of
      atherosclerosis. We previously found a deleterious effect of hyperhomocysteinemia
      on expression of DYRK1A, a Down-syndrome-associated kinase. As increased
      expression of DYRK1A and low plasma homocysteine level have been associated with
      Down syndrome, we aimed to analyze the effect of its over-expression on
      homocysteine metabolism in mice. METHODOLOGY/PRINCIPAL FINDINGS: Effects of
      DYRK1A over-expression were examined by biochemical analysis of methionine
      metabolites, real-time quantitative reverse-transcription polymerase chain
      reaction, and enzyme activities. We found that over-expression of Dyrk1a
      increased the hepatic NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine
      hydrolase activities, concomitant with decreased level of plasma homocysteine in
      three mice models overexpressing Dyrk1a. Moreover, these effects were abolished
      by treatment with harmine, the most potent and specific inhibitor of Dyrk1a. The
      increased NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine hydrolase
      activities were also found in lymphoblastoid cell lines from patients with Down
      syndrome. CONCLUSIONS/SIGNIFICANCE: Our results might give clues to understand
      the protective effect of Down syndrome against vascular defect through a decrease
      of homocysteine level by DYRK1A over-expression. They reveal a link between the
      Dyrk1a signaling pathway and the homocysteine cycle.

PMID- 19844573
TI  - MicroRNA miR-378 regulates nephronectin expression modulating osteoblast
      differentiation by targeting GalNT-7.
AB  - MicroRNAs (miRNAs) are small fragments of single-stranded RNA containing 18-24
      nucleotides, and are generated from endogenous transcripts. MicroRNAs function in
      post-transcriptional gene silencing by targeting the 3'-untranslated region (UTR)
      of mRNAs, resulting in translational repression. We have developed a system to
      study the role of miRNAs in cell differentiation. We have found that one of the
      miRNAs tested in our system (miR-378, also called miR-378*) plays a role in
      modulating nephronectin-mediated differentiation in the osteoblastic cell line,
      MC3T3-E1. Nephronectin is an extracellular matrix protein, and we have
      demonstrated that its over-expression enhanced osteoblast differentiation and
      bone nodule formation. Furthermore, we found that the nephronectin 3'
      untranslated region (3'UTR) contains a binding site for miR-378. Stable
      transfection of MC3T3-E1 cells with miR-378 inhibited cell differentiation. MC3T3
      E1 cells stably transfected with nephronectin exhibited higher rates of
      differentiation and nodule formation as compared with cells transfected with
      nephronectin containing the 3'UTR in the early stages of development, suggesting
      that endogenous miR-378 is present and active. However, in the later stages of
      MC3T3-E1 development, the differentiation rates were opposite, with higher rates
      of differentiation and nodule formation in the cells over-expressing the 3'UTR of
      nephronectin. This appeared to be the consequence of competition between
      nephronectin and UDP-N-acetyl-alpha-D-galactosamine:polypeptide N
      acetylgalactosaminyltransferase 7 (GalNAc-T7 or GalNT7) for miR-378 binding,
      resulting in increased GalNT7 activity, which in turn lead to increased
      nephronectin glycosylation and product secretion, thereby resulting in a higher
      rate of osteoblast differentiation.

PMID- 19844574
TI  - Substrate utilization by the failing human heart by direct quantification using
      arterio-venous blood sampling.
AB  - Metabolic substrate utilization of the human failing heart is an area of
      controversy. The purpose of this study is to directly quantify myocardial
      substrate utilization in moderately severe heart failure, type 2 diabetes and
      healthy controls using simultaneous coronary sinus and arterial blood sampling.
      Patients with heart failure (n = 9, mean NYHA 2.7+/-0.5), with type 2 diabetes (n
      = 5) and with normal heart function (n = 10) were studied after an overnight fast
      in connection with electrophysiological investigations/treatments.A systemic
      infusion of [(2)H(2)]palmitate allowed for the calculation of absolute palmitate
      extraction across the heart. Blood samples were analysed for non-esterified fatty
      acids, triacylglycerol, glycerol, glucose, pyruvate, lactate, 3-hydroxybutyrate,
      and blood gases after simultaneous sampling of arterial and coronary sinus blood.
      Arterio-coronary sinus metabolite concentration differences and fractional
      extractions for all substrates were similar between the groups. The absolute NEFA
      uptakes assessed by [(2)H(2)]palmitate extraction were also similar between the
      groups. Using direct measurements of metabolic substrate uptake by arterio-venous
      difference technique, the compensated human failing heart does not appear to have
      reduced myocardial fatty acid uptake.

PMID- 19844575
TI  - Discovery of the largest orbweaving spider species: the evolution of gigantism in
      Nephila.
AB  - BACKGROUND: More than 41,000 spider species are known with about 400-500 added
      each year, but for some well-known groups, such as the giant golden orbweavers,
      Nephila, the last valid described species dates from the 19(th) century. Nephila
      are renowned for being the largest web-spinning spiders, making the largest orb
      webs, and are model organisms for the study of extreme sexual size dimorphism
      (SSD) and sexual biology. Here, we report on the discovery of a new, giant
      Nephila species from Africa and Madagascar, and review size evolution and SSD in
      Nephilidae. METHODOLOGY: We formally describe N. komaci sp. nov., the largest web
      spinning species known, and place the species in phylogenetic context to
      reconstruct the evolution of mean size (via squared change parsimony). We then
      test female and male mean size correlation using phylogenetically independent
      contrasts, and simulate nephilid body size evolution using Monte Carlo
      statistics. CONCLUSIONS: Nephila females increased in size almost monotonically
      to establish a mostly African clade of true giants. In contrast, Nephila male
      size is effectively decoupled and hovers around values roughly one fifth of
      female size. Although N. komaci females are the largest Nephila yet discovered,
      the males are also large and thus their SSD is not exceptional.

PMID- 19844577
TI  - New episodic learning interferes with the reconsolidation of autobiographical
      memories.
AB  - It is commonly assumed that, with time, an initially labile memory is transformed
      into a permanent one via a process of consolidation. Yet, recent evidence
      indicates that memories can return to a fragile state again when reactivated,
      requiring a period of reconsolidation. In the study described here, we found that
      participants who memorized a story immediately after they had recalled neutral
      and emotional experiences from their past were impaired in their memory for the
      neutral (but not for the emotional) experiences one week later. The effect of
      learning the story depended critically on the preceding reactivation of the
      autobiographical memories since learning without reactivation had no effect.
      These results suggest that new learning impedes the reconsolidation of neutral
      autobiographical memories.

PMID- 19844576
TI  - Manganese enhances prion protein survival in model soils and increases prion
      infectivity to cells.
AB  - Prion diseases are considered to be transmissible. The existence of sporadic
      forms of prion diseases such as scrapie implies an environmental source for the
      infectious agent. This would suggest that under certain conditions the prion
      protein, the accepted agent of transmission, can survive in the environment. We
      have developed a novel technique to extract the prion protein from soil matrices.
      Previous studies have suggested that environmental manganese is a possible risk
      factor for prion diseases. We have shown that exposure to manganese is a soil
      matrix causes a dramatic increase in prion protein survival (approximately 10
      fold) over a two year period. We have also shown that manganese increases
      infectivity of mouse passaged scrapie to culture cells by 2 logs. These results
      clearly verify that manganese is a risk factor for both the survival of the
      infectious agent in the environment and its transmissibility.

PMID- 19844578
TI  - The pentameric vertex proteins are necessary for the icosahedral carboxysome
      shell to function as a CO2 leakage barrier.
AB  - BACKGROUND: Carboxysomes are polyhedral protein microcompartments found in many
      autotrophic bacteria; they encapsulate the CO(2) fixing enzyme, ribulose-1,5
      bisphosphate carboxylase/oxygenase (RubisCO) within a thin protein shell and
      provide an environment that enhances the catalytic capabilities of the enzyme.
      Two types of shell protein constituents are common to carboxysomes and related
      microcompartments of heterotrophic bacteria, and the genes for these proteins are
      found in a large variety of bacteria. METHODOLOGY/PRINCIPAL FINDINGS: We have
      created a Halothiobacillus neapolitanus knockout mutant that does not produce the
      two paralogous CsoS4 proteins thought to occupy the vertices of the icosahedral
      carboxysomes and related microcompartments. Biochemical and ultrastructural
      analyses indicated that the mutant predominantly forms carboxysomes of normal
      appearance, in addition to some elongated microcompartments. Despite their normal
      shape, purified mutant carboxysomes are functionally impaired, although the
      activities of the encapsulated enzymes are not negatively affected.
      CONCLUSIONS/SIGNIFICANCE: In the absence of the CsoS4 proteins the carboxysome
      shell loses its limited permeability to CO(2) and is no longer able to provide
      the catalytic advantage RubisCO derives from microcompartmentalization. This
      study presents direct evidence that the diffusion barrier property of the
      carboxysome shell contributes significantly to the biological function of the
      carboxysome.

PMID- 19844579
TI  - Analysis of group randomized trials with multiple binary endpoints and small
      number of groups.
AB  - The group randomized trial (GRT) is a common study design to assess the effect of
      an intervention program aimed at health promotion or disease prevention. In GRTs,
      groups rather than individuals are randomized into intervention or control arms.
      Then, responses are measured on individuals within those groups. A number of
      analytical problems beset GRT designs. The major problem emerges from the likely
      positive intraclass correlation among observations of individuals within a group.
      This paper provides an overview of the analytical method for GRT data and applies
      this method to a randomized cancer prevention trial, where multiple binary
      primary endpoints were obtained. We develop an index of extra variability to
      investigate group-specific effects on response. The purpose of the index is to
      understand the influence of individual groups on evaluating the intervention
      effect, especially, when a GRT study involves a small number of groups. The
      multiple endpoints from the GRT design are analyzed using a generalized linear
      mixed model and the stepdown Bonferroni method of Holm.

PMID- 19844580
TI  - A statistical model of protein sequence similarity and function similarity
      reveals overly-specific function predictions.
AB  - BACKGROUND: Predicting protein function from primary sequence is an important
      open problem in modern biology. Not only are there many thousands of proteins of
      unknown function, current approaches for predicting function must be improved
      upon. One problem in particular is overly-specific function predictions which we
      address here with a new statistical model of the relationship between protein
      sequence similarity and protein function similarity. METHODOLOGY: Our statistical
      model is based on sets of proteins with experimentally validated functions and
      numeric measures of function specificity and function similarity derived from the
      Gene Ontology. The model predicts the similarity of function between two proteins
      given their amino acid sequence similarity measured by statistics from the BLAST
      sequence alignment algorithm. A novel aspect of our model is that it predicts the
      degree of function similarity shared between two proteins over a continuous range
      of sequence similarity, facilitating prediction of function with an appropriate
      level of specificity. SIGNIFICANCE: Our model shows nearly exact function
      similarity for proteins with high sequence similarity (bit score >244.7, e-value
      >1e(-62), non-redundant NCBI protein database (NRDB)) and only small likelihood
      of specific function match for proteins with low sequence similarity (bit score
      <54.6, e-value <1e(-05), NRDB). For sequence similarity ranges in between our
      annotation model shows an increasing relationship between function similarity and
      sequence similarity, but with considerable variability. We applied the model to a
      large set of proteins of unknown function, and predicted functions for thousands
      of these proteins ranging from general to very specific. We also applied the
      model to a data set of proteins with previously assigned, specific functions that
      were electronically based. We show that, on average, these prior function
      predictions are more specific (quite possibly overly-specific) compared to
      predictions from our model that is based on proteins with experimentally
      determined function.

PMID- 19844581
TI  - Converting redox signaling to apoptotic activities by stress-responsive
      regulators HSF1 and NRF2 in fenretinide treated cancer cells.
AB  - BACKGROUND: Pharmacological intervention of redox balance in cancer cells often
      results in oxidative stress-mediated apoptosis, attracting much attention for the
      development of a new generation of targeted therapy in cancer. However, little is
      known about mechanisms underlying the conversion from oxidative signaling to
      downstream activities leading cells to death. METHODOLOGY/PRINCIPAL FINDINGS: We
      here report a systematic detection of transcriptome changes in response to
      oxidative signals generated in leukemia cells upon fenretinide treatment,
      implicating the occurrence of numerous stress-responsive events during the
      fenretinide induced apoptosis, such as redox response, endoplasmic reticulum
      stress/unfolded protein response, translational repression and proteasome
      activation. Moreover, the configuration of these relevant events is primarily
      orchestrated by stress responsive transcription factors, as typically highlighted
      by NF-E2-related factor-2 (NRF2) and heat shock factor 1 (HSF1). Several lines of
      evidence suggest that the coordinated regulation of these transcription factors
      and thus their downstream genes are involved in converting oxidative signaling
      into downstream stress-responsive events regulating pro-apoptotic and apoptotic
      activities at the temporal and spatial levels, typifying oxidative stress
      mediated programmed death rather than survival in cancer cells.
      CONCLUSIONS/SIGNIFICANCE: This study provides a roadmap for understanding
      oxidative stress-mediated apoptosis in cancer cells, which may be further
      developed into more sophisticated therapeutic protocols, as implicated by
      synergistic induction of cell apoptosis using proteasome inhibitors with
      fenretinide.

PMID- 19844582
TI  - Cross-talk between signaling pathways can generate robust oscillations in calcium
      and cAMP.
AB  - BACKGROUND: To control and manipulate cellular signaling, we need to understand
      cellular strategies for information transfer, integration, and decision-making. A
      key feature of signal transduction is the generation of only a few intracellular
      messengers by many extracellular stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      model molecular cross-talk between two classic second messengers, cyclic AMP
      (cAMP) and calcium, and show that the dynamical complexity of the response of
      both messengers increases substantially through their interaction. In our model
      of a non-excitable cell, both cAMP and calcium concentrations can oscillate. If
      mutually inhibitory, cross-talk between the two second messengers can increase
      the range of agonist concentrations for which oscillations occur. If mutually
      activating, cross-talk decreases the oscillation range, but can generate
      'bursting' oscillations of calcium and may enable better filtering of noise.
      CONCLUSION: We postulate that this increased dynamical complexity allows the cell
      to encode more information, particularly if both second messengers encode
      signals. In their native environments, it is unlikely that cells are exposed to
      one stimulus at a time, and cross-talk may help generate sufficiently complex
      responses to allow the cell to discriminate between different combinations and
      concentrations of extracellular agonists.

PMID- 19844583
TI  - Dominance, politics, and physiology: voters' testosterone changes on the night of
      the 2008 United States presidential election.
AB  - BACKGROUND: Political elections are dominance competitions. When men win a
      dominance competition, their testosterone levels rise or remain stable to resist
      a circadian decline; and when they lose, their testosterone levels fall. However,
      it is unknown whether this pattern of testosterone change extends beyond
      interpersonal competitions to the vicarious experience of winning or losing in
      the context of political elections. Women's testosterone responses to dominance
      competition outcomes are understudied, and to date, a clear pattern of
      testosterone changes in response to winning and losing dominance competitions has
      not emerged. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated
      voters' testosterone responses to the outcome of the 2008 United States
      Presidential election. 183 participants provided multiple saliva samples before
      and after the winner was announced on Election Night. The results show that male
      Barack Obama voters (winners) had stable post-outcome testosterone levels,
      whereas testosterone levels dropped in male John McCain and Robert Barr voters
      (losers). There were no significant effects in female voters.
      CONCLUSIONS/SIGNIFICANCE: The findings indicate that male voters exhibit
      biological responses to the realignment of a country's dominance hierarchy as if
      they participated in an interpersonal dominance contest.

PMID- 19844584
TI  - Involvement of the intrinsic/default system in movement-related self recognition.
AB  - The question of how people recognize themselves and separate themselves from the
      environment and others has long intrigued philosophers and scientists. Recent
      findings have linked regions of the 'default brain' or 'intrinsic system' to self
      related processing. We used a paradigm in which subjects had to rely on subtle
      sensory-motor synchronization differences to determine whether a viewed movement
      belonged to them or to another person, while stimuli and task demands associated
      with the "responded self" and "responded other" conditions were precisely
      matched. Self recognition was associated with enhanced brain activity in several
      ROIs of the intrinsic system, whereas no differences emerged within the extrinsic
      system. This self-related effect was found even in cases where the sensory-motor
      aspects were precisely matched. Control conditions ruled out task difficulty as
      the source of the differential self-related effects. The findings shed light on
      the neural systems underlying bodily self recognition.

PMID- 19844585
TI  - Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell
      cycle progression.
AB  - Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and
      glucose metabolism. Akt is differentially activated by growth factors and
      oxidative stress by sequential phosphorylation of Ser(473) by mTORC2 and Thr(308)
      by PDK1. On these bases, we investigated the mechanistic connection of H(2)O(2)
      yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3
      cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We
      demonstrate that modulation by H(2)O(2) entails the entrance of cytosolic P-Akt1
      Ser(473) to mitochondria, where it is further phosphorylated at Thr(308) by
      constitutive PDK1. Phosphorylation of Thr(308) in mitochondria determines Akt1
      passage to nuclei and triggers genomic post-translational mechanisms for cell
      proliferation. At high H(2)O(2), Akt1-PDK1 association is disrupted and P-Akt1
      Ser(473) accumulates in mitochondria in detriment to nuclear translocation;
      accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases
      cytochrome c release to cytosol leading to apoptosis. As assessed by mass
      spectra, differential H(2)O(2) effects on Akt1-PDK interaction depend on the
      selective oxidation of Cys(310) to sulfenic or cysteic acids. These results
      indicate that Akt1 intramitochondrial-cycling is central for redox modulation of
      cell fate.

PMID- 19844586
TI  - An evaluation of OPTC and EPYC as candidate genes for high myopia.
AB  - PURPOSE: The small leucine-rich repeat proteins (SLRPs) are involved in
      organizing the collagen fibrils of the sclera and vitreous. The shape of the
      eyeball is determined by the sclera and vitreous, so defects in SLRP family
      members may contribute to myopia. The purpose of this study was to test whether
      mutations in the two members of the class III SLRPs, opticin (OPTC) and dermatan
      sulfate proteoglycan 3 (EPYC), are responsible for high myopia. METHODS: DNA was
      prepared from venous leukocytes of 93 patients with high myopia (refraction of
      spherical equivalent <or=-6.00D) and 96 controls (refraction of spherical
      equivalent between -0.50D and +1.00D). The coding regions and adjacent intronic
      sequences of OPTC and EPYC were amplified by the polymerase chain reaction (PCR),
      and the products were then analyzed by cycle sequencing. The detected variations
      were further evaluated in normal controls and available family members by a
      heteroduplex-single strand conformation polymorphism (heteroduplex-SSCP) analysis
      or sequencing. RESULTS: Two substitutions in OPTC, including c.491G>T and
      c.803T>C, were identified. The c.491G>T mutation (p.Arg164Leu), a novel
      heterozygous variation, was detected in one of the 93 patients but in none of the
      96 controls. The c.803T>C mutation (p.Pro267Leu), a known polymorphism, was
      detected in 22 of the 93 patients and in 15 of 48 controls. No variation was
      observed in EPYC. CONCLUSIONS: Only one novel variation in OPTC was detected in a
      Chinese patient with high myopia. Our results imply that OPTC and EPYC are
      unlikely to play a major role in high myopia.

PMID- 19844587
TI  - In vivo evaluation of a novel scaffold for artificial corneas prepared by using
      ultrahigh hydrostatic pressure to decellularize porcine corneas.
AB  - PURPOSE: To evaluate the stability and biocompatibility of artificial corneal
      stroma that was prepared by using ultrahigh hydrostatic pressurization treatment
      to decellularize corneas. METHODS: The porcine cornea was decellularized by two
      methods, a detergent method and an ultrahigh hydrostatic pressure (UHP) method.
      Either 1% w/v Triton X-100 or sodium dodecyl sulfate (SDS) was used for the
      detergent method, and 10,000 atmospheres (atm; 7.6x10(6) mmHg) was applied to the
      cornea for 10 min at 10 degrees C by a high-pressure machine for the UHP method.
      Hematoxylin-eosin staining was performed to confirm the removal of the corneal
      cells, and then decellularized porcine corneal stroma was implanted into rabbit
      corneal pockets. After eight weeks, the rabbit eyes were enucleated to examine
      the tissue compatibility of the implanted stroma. RESULTS: Complete
      decellularization was confirmed only in corneas treated by the UHP method, and
      little inflammation was seen when they were implanted into the rabbit corneal
      pockets. CONCLUSIONS: Porcine corneal stroma completely decellularized by the UHP
      method has extremely high biocompatibility and is a possible corneal scaffold for
      an artificial cornea.

PMID- 19844588
TI  - Effects of mitomycin C on the expression of chymase and mast cells in the
      conjunctival scar of a monkey trabeculectomy model.
AB  - PURPOSE: To determine the effects of mitomycin C (MMC) on the expression of
      chymase and mast cells in the conjunctival scar after trabeculectomy. METHODS:
      Ten eyes of five monkeys were used. Three eyes underwent trabeculectomy with MMC
      (MMC-treated), four eyes had trabeculectomy without MMC (placebo-treated), and
      three eyes served as control eyes. Intraocular pressure was measured before and
      three weeks after surgery. The scores of the degree of conjunctival adhesion were
      evaluated. Immunohistochemistry was used to analyze the densities of
      proliferative cell nuclear antigen-positive cells, chymase-positive cells, and
      mast cells. The ratio of collagen fiber areas to conjunctival and scleral lesions
      was analyzed by Mallory-Azan staining. RESULTS: After trabeculectomy, the
      intraocular pressure reduction of MMC-treated eyes was significantly different
      from placebo-treated and control eyes (p=0.032, 0.035). The adhesion score of MMC
      treated eyes was also significantly lower than that of placebo-treated eyes
      (p=0.034). Densities of proliferative cell nuclear antigen-positive cells,
      chymase-positive cells, and areas of collagen fiber in conjunctival and scleral
      lesions were significantly decreased in MMC-treated eyes, compared with placebo
      treated eyes (p=0.034, 0.034, 0.049, respectively). There was a tendency for the
      density of mast cells to be suppressed in MMC-treated eyes (p=0.157).
      CONCLUSIONS: Chymase might be involved in one of the mechanisms by which MMC
      suppresses scar formation after trabeculectomy.

PMID- 19844589
TI  - Nerve growth factor modulates toll-like receptor (TLR) 4 and 9 expression in
      cultured primary VKC conjunctival epithelial cells.
AB  - PURPOSE: To investigate if nerve growth factor (NGF) might modulate toll-like
      receptor (TLR) 4 and 9 expression in primary cultures of vernal
      keratoconjunctivitis (VKC)-derived conjunctival epithelial cells (VKC-ECs).
      METHODS: Primary cultures of ECs were established from VKC (n=7) and healthy
      control (n=5) conjunctival specimens. Primary untouched and short-term NGF
      exposed VKC-ECs were analyzed for molecular (relative real-time PCR) and
      biochemical (confocal and fluorescence-activated cell sorting analysis of TLR4
      and TLR9 expression. Data were compared to their untreated as well as stimulated
      healthy-control counterparts. Conditioned media were analyzed for interferon
      (IFN)-gamma, interleukin (IL)-4, IL-10, and IL-12 p40 secretion. RESULTS: Primary
      untouched VKC-ECs showed TLR4 increase and TLR9 decrease compared to their
      healthy-control counterparts. NGF exposure resulted in a strong upregulation of
      TLR4 and a moderate upregulation of TLR9 in few passages VKC-ECs. Both TLR4 and
      TLR9 upregulation occurred in a dose-dependent fashion and were supported by
      biochemical analysis. NGF triggered a dose-response release of IL-10 in VKC-ECs
      conditioned media, an effect not detected for IL-4, IL-12 p40, and IFN-gamma.
      CONCLUSIONS: Our data indicate that NGF is able to induce TLR4/TLR9
      overexpression in VKC-ECs. These cells exhibited poor IL-4, IL-12 p40, and IFN
      gamma responses to NGF, while a significant IL-10 decreased secretion was
      detected. The different NGF-induced TLR response between VKC and healthy-control
      conjunctival ECs as well as the different cytokine response might reflect a
      different pattern of cell activation according to the state of VKC.

PMID- 19844590
TI  - Antimicrobial properties of green tea catechins.
AB  - Extracts of leaves from the tea plant Camellia sinensis contain polyphenolic
      components with activity against a wide spectrum of microbes. Studies conducted
      over the last 20 years have shown that the green tea polyphenolic catechins, in
      particular (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin gallate (ECg),
      can inhibit the growth of a wide range of Gram-positive and Gram-negative
      bacterial species with moderate potency. Evidence is emerging that these
      molecules may be useful in the control of common oral infections, such as dental
      caries and periodontal disease. Sub-inhibitory concentrations of EGCg and ECg can
      suppress the expression of bacterial virulence factors and can reverse the
      resistance of the opportunistic pathogen Staphylococcus aureus to beta-lactam
      antibiotics. For example, relatively low concentrations of ECg can sensitize
      methicillin-resistant S. aureus (MRSA) clinical isolates to levels of oxacillin
      that can be readily achieved in clinical practice. Catechin gallates such as ECg
      intercalate into phopsholipid bilayers and it is likely that they affect both
      virulence and antibiotic resistance by perturbing the function of key processes
      associated with the bacterial cytoplasmic membrane.

PMID- 19844592
TI  - Synthesis of Phosphatidylcholine Analogues Derived from Glyceric Acid: a New
      Class of Biologically Active Phospholipid Compounds.
AB  - Synthesis of a new class of phosphatidylcholine analogues derived from glyceric
      acid is reported for spectroscopic studies of phospholipases and conformation of
      phospholipid side-chains in biological membranes, using fluorescence resonance
      energy transfer (FRET) techniques.

PMID- 19844591
TI  - Bridging the Gap Between Genomics and Education.
AB  - Despite several decades of research suggesting the importance of both genetic and
      environmental factors, these findings are not well integrated into the larger
      educational literature. Following a discussion of quantitative and molecular
      genetic methods, this article reviews behavioral genetic findings related to
      cognitive and academic skills. This literature suggests that (a) the relative
      importance of genes and environments varies developmentally; (b) genetics, and to
      a lesser extend the environment, account for a substantial portion of the
      covariance within and across academic domains; and (c) some forms of disability
      are qualitatively different from the population, whereas others constitute the
      lower end of a continuum of ability. Following a discussion of the strengths and
      limitations of current behavioral genetic research and intervention research, we
      then discuss the ways in which understanding gene -environment interplay can be
      used to develop better definitions of learning impairment and better explain the
      substantial variability in response to intervention.

PMID- 19844593
TI  - Determining Surface Plasmon Resonance Response Factors for Deposition onto Three
      Dimensional Surfaces.
AB  - Intrinsic sorption rates of ligand/receptor binding have been measured by surface
      plasmon resonance (SPR) using response factors for deposition of proteins or
      smaller molecules on planar surfaces. In this study generalized expressions for
      SPR response factor and effective refractive index are developed to measure rates
      of analyte sorption onto 3-D surfaces. The expressions are specialized for two
      limiting cases of immediate practical interest and broad applicability: analyte
      deposition onto a homogeneous anisotropic porous media and deposition onto close
      packed solid spheres adjacent to the sensor surface. These new equations specify
      media capacity, characteristic size and analyte concentration that are necessary
      to obtain identifiable responses from interaction with anisotropic porous media
      or chromatographic resin. These developments are illustrated by comparing
      response factors for Adenovirus Type 5 on planar surfaces, porous media and
      adsorptive spheres.

PMID- 19844594
TI  - Salivary protein factors are elevated in breast cancer patients.
AB  - While saliva is a source of easily accessible bodily fluids, there has been
      little effort to study its value in cancer diagnosis. We hypothesized that
      certain proteins would be elevated in the saliva of patients with breast cancer.
      Our study included 49 healthy individuals and 49 breast cancer patients. The
      levels of vascular endothelial growth factor (VEGF), epidermal growth factor
      (EGF) and carcinoembryonic antigen (CEA) in the saliva were measured with enzyme
      linked immunosorbent assay (ELISA). We observed that salivary fluid protein
      levels were significantly elevated in cancer patients as follows: i) VEGF, 3.7+/
      1.6 in cancer versus 2.1+/-1.2 ng/ml in control (p<0.0001); ii) EGF, 3.7+/-1.7
      versus 2.1+/-1.3 ng/ml (p<0.0001); and iii) CEA, 83+/-31 versus 66.1+/-27.1 ng/ml
      (p=0.0106). The areas under the receiver operating characteristic (ROC) curve
      (AUC) were 80, 77 and 65%, respectively. The best prediction was from the
      combination of salivary VEGF and EGF with a sensitivity of 83%, specificity of
      74% and AUC of 84%. We conclude that saliva is a novel avenue for tumor marker
      research and deserves further studies. Saliva may potentially be useful in
      supplementing current methods of breast cancer detection.

PMID- 19844596
TI  - Cognitive influences on risk-seeking by rhesus macaques.
AB  - Humans and other animals are idiosyncratically sensitive to risk, either
      preferring or avoiding options having the same value but differing in
      uncertainty. Many explanations for risk sensitivity rely on the non-linear shape
      of a hypothesized utility curve. Because such models do not place any importance
      on uncertainty per se, utility curve-based accounts predict indifference between
      risky and riskless options that offer the same distribution of rewards. Here we
      show that monkeys strongly prefer uncertain gambles to alternating rewards with
      the same payoffs, demonstrating that uncertainty itself contributes to the appeal
      of risky options. Based on prior observations, we hypothesized that the appeal of
      the risky option is enhanced by the salience of the potential jackpot. To test
      this, we subtly manipulated payoffs in a second gambling task. We found that
      monkeys are more sensitive to small changes in the size of the large reward than
      to equivalent changes in the size of the small reward, indicating that they
      attend preferentially to the jackpots. Together, these results challenge utility
      curve-based accounts of risk sensitivity, and suggest that psychological factors,
      such as outcome salience and uncertainty itself, contribute to risky decision
      making.

PMID- 19844595
TI  - Sub-millimeter resolution 3D optical imaging of living tissue using laminar
      optical tomography.
AB  - In-vivo imaging of optical contrast in living tissues can allow measurement of
      functional parameters such as blood oxygenation and detection of targeted and
      active fluorescent contrast agents. However, optical imaging must overcome the
      effects of light scattering, which limit the penetration depth and can affect
      quantitation and sensitivity. This article focuses on a technique for high
      resolution, high-speed depth-resolved optical imaging of superficial living
      tissues called laminar optical tomography (LOT), which is capable of imaging
      absorbing and fluorescent contrast in living tissues to depths of 2-3 mm with 100
      200 micron resolution. An overview of the advantages and challenges of in-vivo
      optical imaging is followed by a review of currently available techniques for
      high-resolution optical imaging of tissues. LOT is then described, including a
      description of the imaging system design and discussion of data analysis and
      image reconstruction approaches. Examples of recent applications of LOT are then
      provided and compared to other existing technologies.By measuring multiply
      scattered light, Laminar Optical Tomography can probe beneath the surface of
      living tissues such as the skin and brain.

PMID- 19844597
TI  - Structure determination and absolute configuration of cannabichromanone
      derivatives from high potency Cannabis sativa.
AB  - Three new cannabichromanone derivatives were isolated from high potency cannabis,
      along with the known cannabichromanone. Full spectroscopic data, including the
      use of electronic circular dichroism and Mosher ester analysis to determine the
      absolute configuration of these compounds, are reported. All isolates were tested
      for antimicrobial, antimalarial, antileishmanial and anti-oxidant activity.

PMID- 19844598
TI  - What have we been priming all these years? On the development, mechanisms, and
      ecology of nonconscious social behavior.
AB  - Priming or nonconscious activation of social knowledge structures has produced a
      plethora of rather amazing findings over the past 25 years: priming a single
      social concept such as aggressive can have multiple effects across a wide array
      of psychological systems, such as perception, motivation, behavior, and
      evaluation. But we may have reached childhood's end, so to speak, and need now to
      move on to research questions such as how these multiple effects of single primes
      occur (the generation problem); next, how these multiple simultaneous priming
      influences in the environment get distilled into nonconscious social action that
      has to happen serially, in real time (the reduction problem). It is suggested
      that models of complex conceptual structures (Lakoff & Johnson, 1980), language
      use in real-life conversational settings (Clark, 1996), and speech production
      (Dell, 1986) might hold the key for solving these two important 'second
      generation' research problems.

PMID- 19844599
TI  - Replication of Functional MRI Detection of Deception.
AB  - BACKGROUND: Several studies support the use of fMRI for detecting deception.
      There have been, however, no reported replications on different scanners or at
      different locations. In a previous study, deception was accurately detected in at
      least 90% of the participants in two independent cohorts. This study attempted to
      replicate those findings using a different scanner and location. METHODS: Healthy
      participants 18-50 years of age were recruited from the local community. After
      providing written informed consent, participants were screened to ensure that
      they were healthy, not taking any medications, and safe to have an MRI. For the
      testing paradigm, subjects chose one of two objects (ring or watch) to "steal"
      and placed it in their locker. Participants were then scanned while being
      visually presented with a series of questions. Functional MRI analysis was
      performed in the same manner as described in Kozel et al. 2005. A Chi-Squared
      test was used to test for a significant difference between the results in the
      previous study and in this replication study. RESULTS: Thirty subjects (20 women,
      mean age 29.0+/-6.5 years) were scanned with one subject being noncompliant with
      the protocol. Twenty-five of twenty-nine (86%) participants were correctly
      identified when being deceptive. There was no statistical difference between the
      accuracy rate obtained in this study (25/29) versus the previous study (28/31)
      (Chi-Squared, chi(2)=0.246, p=0.6197). CONCLUSIONS: Our methodology for detecting
      deception was successfully replicated at a different site suggesting that this
      methodology is robust and independent of both scanner and location.

PMID- 19844600
TI  - Chromatic-Spatial Vision of the Aging Eye.
AB  - The human visual system undergoes continuous anatomical, physiological and
      functional changes throughout the life span. There is also continuous change in
      the spectral distribution and intensity of light reaching the retina from infancy
      through senescence, primarily due to changes in the absorption of short-wave
      light by the lens. Despite these changes in the retinal stimulus and the signals
      leaving the retina for perceptual analysis, color appearance is relatively stable
      during aging as measured by broadband reflective or self-luminous samples, the
      wavelengths of unique blue and yellow, and the achromatic locus. Measures of
      ocular media density for younger and older observers show, indeed, that color
      appearance is independent of ocular media density. This may be explained by a
      renormalization process that was demonstrated by measuring the chromaticity of
      the achromatic point before and after cataract surgery. There was a shift
      following cataract surgery (removal of a brunescent lens) that was initially
      toward yellow in color space, but over the course of months, drifted back in the
      direction of the achromatic point before surgery. The spatial characteristics of
      color mechanisms were quantified for younger and older observers in terms of
      chromatic perceptive fields and the chromatic contrast sensitivity functions.
      Younger and older observers differed with small spots or with chromatic spatial
      gratings near threshold, but there were no significant differences with larger
      spots or suprathreshold spatial gratings.

PMID- 19844601
TI  - The Future of Psychology: Connecting Mind to Brain.
AB  - Psychological states such as thoughts and feelings are real. Brain states are
      real. The problem is that the two are not real in the same way, creating the mind
      brain correspondence problem. In this article, I present a possible solution to
      this problem that involves two suggestions. First, complex psychological states
      such as emotion and cognition can be thought of as constructed events that can be
      causally reduced to a set of more basic, psychologically primitive ingredients
      that are more clearly respected by the brain. Second, complex psychological
      categories like emotion and cognition are the phenomena that require explanation
      in psychology, and, therefore, they cannot be abandoned by science. Describing
      the content and structure of these categories is a necessary and valuable
      scientific activity. 

PMID- 19844602
TI  - ADE-FDTD Scattered-Field Formulation for Dispersive Materials.
AB  - This Letter presents a scattered-field formulation for modeling dispersive media
      using the finite-difference time-domain (FDTD) method. Specifically, the
      auxiliary differential equation method is applied to Drude and Lorentz media for
      a scattered field FDTD model. The present technique can also be applied in a
      straightforward manner to Debye media. Excellent agreement is achieved between
      the FDTD-calculated and exact theoretical results for the reflection coefficient
      in half-space problems.

PMID- 19844603
TI  - Best Friendships, Group Relationships, and Antisocial Behavior in Early
      Adolescence.
AB  - Correlations between adolescents' own antisocial behavior and adolescents'
      perceptions of the antisocial behavior of their best friends and friendship
      groups were examined in this study. The strength of those correlations was
      expected to vary as a function of the qualities of the dyadic friendships and
      group relationships. Perceptions of peers' antisocial behavior and dyadic
      friendship and group relationship qualities were collected through interviews
      with 431, 12- through 13-year-old adolescents. Measures of adolescents'
      concurrent and subsequent antisocial behaviors were obtained from the adolescents
      and their teachers. Adolescents who perceived their friends and groups as
      participating in antisocial behavior had higher self-reported and teacher
      reported antisocial behavior ratings. Perceptions of best friend antisocial
      behavior were correlated more strongly with adolescents' own concurrent, but not
      subsequent, antisocial behavior when high levels of help, companionship, and
      security characterized dyadic friendships. The results are discussed in terms of
      peer influence and friendship selection processes.

PMID- 19844604
TI  - Morphogenesis of Coronavirus HCoV-NL63 in Cell Culture: A Transmission Electron
      Microscopic Study.
AB  - NL63 (HCoV-NL63) is a recently discovered human coronavirus that causes
      respiratory disease in infants and young children. NL63 productively infects
      LLCMK2 cells and ciliated epithelial cells of human airway cell cultures.
      Transmission electron microscopic (TEM) studies of NL63 infected LLCMK2 cells
      revealed that virions are spherical, spiked, and range from 75 to 115 nm in
      diameter. Virus replication predominantly occurs on the rough endoplasmic
      reticulum (RER), both perinuclear and cytoplasmic, and the Golgi. Plasma membrane
      budding was occasionally observed. As virus production increased, aberrant viral
      forms appeared with greater frequency. Unusual inclusions were present in
      infected cells including tubular and laminated structures. Pleomorphic double
      membrane-bound vesicles (DMV), measuring roughly 140 to 210 nm in diameter, were
      observed. The virus was released via exocytosis and cell lysis. In summary, we
      report the key morphologic characteristics of NL63 infection observed by TEM
      analysis.

PMID- 19844606
TI  - Testing Equality of Survival Distributions when the Population Marks are Missing.
AB  - This paper introduces a nonparametric approach for testing the equality of two or
      more survival distributions based on right censored failure times with missing
      population marks for the censored observations. The standard log-rank test is not
      applicable here because the population membership information is not available
      for the right censored individuals. We propose to use the imputed population
      marks for the censored observations leading to fractional at-risk sets that can
      be used in a two sample censored data log-rank test. We demonstrate with a simple
      example that there could be a gain in power by imputing population marks (the
      proposed method) for the right censored individuals compared to simply removing
      them (which also would maintain the right size). Performance of the imputed log
      rank tests obtained this way is studied through simulation. We also obtain an
      asymptotic linear representation of our test statistic. Our testing methodology
      is illustrated using a real data set.

PMID- 19844607
TI  - OVERLAP OF HEARING AND VOICING RANGES IN SINGING.
AB  - Frequency and intensity ranges in voice production by trained and untrained
      singers were superimposed onto the average normal human hearing range. The vocal
      output for all subjects was shown both in Voice Range Profiles and Spectral Level
      Profiles. Trained singers took greater advantage of the dynamic range of the
      auditory system with harmonic energy (45% of the hearing range compared to 38%
      for untrained vocalists). This difference seemed to come from the trained singers
      ablily to exploit the most sensitive part of the hearing range (around 3 to 4
      kHz) through the use of the singer's formant. The trained vocalists' average
      maximum third-octave spectral band level was 95 dB SPL, compared to 80 dB SPL for
      untrained.

PMID- 19844605
TI  - Neuromodulatory processes of the brain-gut axis.
AB  - Brain-gut axis represents a complex reflex circuit that integrates the
      communication between cortex and the digestive system. Disturbances of the
      neuromodulatory processes in the brain-gut axis generate functional digestive
      disorders mainly centered on the pain symptoms and motility disorders. This
      article reviews structural and patho-physiological aspects of the brain-gut axis
      and explains how the neuromodulatory interventions currently used in order to
      treat GI conditions related to the brain-gut axis disturbances. The
      neuromodulation can be realized by pharmacological targeting mainly receptors in
      the periphery or using electrical stimulation applied at different levels of the
      nervous system or directly in the muscular layers of the bowels resulting in
      modulation of the digestive system activity. The efficacy of the methods using
      electrostimulation is dependent on the parameters of the physical system used:
      amplitude, frequency, burst time of the electrical current and also the
      positioning of the electrodes. While pharmacological interventions are largely
      used at the moment, neuromodulatory interventions involving electrical
      stimulation showed clinical efficacy in research trials and have promise.

PMID- 19844608
TI  - Psychosomatic Aspects of Gynecologic Oncology: Present Status and Future
      Directions.
AB  - Among women genital malignancies are second in frequency only to breast cancer.
      Primary disease sites include the endometrium, cervix, ovary, and vulva. With
      early diagnosis and aggressive therapy, two-thirds of these women will survive
      for at least 5 years. This encouraging prognosis is in contrast to the distress
      that may be experienced by women during diagnosis, treatment, and recovery
      periods. A brief review of major avenues of current research and clinical work is
      provided, including; psychological responses to gynecologic cancer
      symptomatology; affective distress; sexual problems; and treatment-related
      distress. Areas for future investigation are highlighted, including difficulties
      occurring with disease recurrence; disruption of close relationships; and
      problems of the elderly woman with cancer.

PMID- 19844609
TI  - Radiation Therapy and Psychological Distress in Gynecologic Oncology Patients:
      Outcomes and Recommendations for Enhancing Adjustment.
AB  - Radiotherapy is used commonly in the treatment of gynecologic malignancies. Many
      patients experience emotional distress prior to the initiation of radiotherapy,
      during the course of treatment, or after the completion of treatment. This paper
      describes treatment experiences from the patients' perspective, reviews the
      empirical data concerning patients' emotional responses to these treatments, and
      overviews strategies for reducing patient distress.

PMID- 19844611
TI  - Rise of the appendage.

PMID- 19844610
TI  - The Intersection of Theory and Application in Elucidating Pattern Formation in
      Developmental Biology.
AB  - We discuss theoretical and experimental approaches to three distinct
      developmental systems that illustrate how theory can influence experimental work
      and vice-versa. The chosen systems - Drosophila melanogaster, bacterial pattern
      formation, and pigmentation patterns - illustrate the fundamental physical
      processes of signaling, growth and cell division, and cell movement involved in
      pattern formation and development. These systems exemplify the current state of
      theoretical and experimental understanding of how these processes produce the
      observed patterns, and illustrate how theoretical and experimental approaches can
      interact to lead to a better understanding of development. As John Bonner said
      long ago'We have arrived at the stage where models are useful to suggest
      experiments, and the facts of the experiments in turn lead to new and improved
      models that suggest new experiments. By this rocking back and forth between the
      reality of experimental facts and the dream world of hypotheses, we can move
      slowly toward a satisfactory solution of the major problems of developmental
      biology.'

PMID- 19844612
TI  - Brain imaging correlates of cognitive impairment in depression.
AB  - This review briefly summarises recent research on the neural basis of cognition
      in depression. Two broad areas are covered: emotional and non-emotional
      processing. We consider how research findings support models of depression based
      on disrupted cortico-limbic circuitry, and how modern connectivity analysis
      techniques can be used to test such models explicitly. Finally we discuss
      clinical implications of cognitive imaging in depression, and specifically the
      possible role for these techniques in diagnosis and treatment planning.

PMID- 19844613
TI  - Emission Behavior of Fluorescently Labeled Silver Nanoshell: Enhanced Self
      Quenching by Metal Nanostructure.
AB  - Labeled silica beads with an average diameter of 100 nm were synthesized by
      incorporating with 20-600 MUM Ru(bpy)(3) (2+) complexes. Silver shells were
      deposited on the beads layer-by-layer with the shell thickness of 5-50 nm. The
      emission band became narrower and the intensity was enhanced depending on the
      shell thickness. Self-quenching of the probe was observed at high concentration.
      Poisson statistics were employed to analyze self-quenching of the fluorophores.
      The estimated quenching distance was extended from 6 to 16 nm with shell growth
      from 0 to 50 nm. Moreover, the silver shells were also labeled with Rhodamine 6G.
      Fluorescence enhancement and reduced lifetime were also observed for silver
      silica shell containing R6G. We found that by adjustment of probe concentration
      and silver shell thickness, a Ru(bpy)(3) (2+)-labeled particle could be 600 times
      brighter than an isolated Ru(bpy)(3) (2+) molecule. We expect labeled metal core
      shell structures can become useful probes for high sensitivity and/or single
      particle assay.

PMID- 19844615
TI  - Pedicular and extrapedicular morphometric analysis in the korean population :
      computed tomographic assessment relevance to pedicle and extrapedicle screw
      fixation in the thoracic spine.
AB  - OBJECTIVE: To evaluate the anatomical parameters that must be considered when
      performing thoracic transpedicular or extrapedicular screw fixation. METHODS: We
      selected 958 vertebrae (1,916 pedicles) from 98 patients for analysis. Eight
      parameters were measured from CT scans : the transverse outer pedicular diameter,
      transverse inner pedicular diameter, length, angle, chord length of the pedicles
      and the transverse width, angle, and chord length of the pedicle-rib units.
      RESULTS: The age of the patients ranged from 21 to 82 years (mean : 48.2 years)
      and there were 57 men and 41 women. The narrowest transverse outer pedicular
      diameter was at T5 (4.4 mm). The narrowest pedicle length was at T1 (15.9 mm).
      For pedicle angle, T1 was 31.6 degrees, which was the most convergent angle, and
      it showed the tendency of the lower the level, the lesser the convergent angle.
      The chord length showed a horizontal pattern with similar values at all levels.
      For the PRU width, T5 showed a similar pattern to the pedicle width at 13.4 mm.
      For the PRU angle, T1 was the largest angle at 46.2 degrees and the tendency was
      the lower the level, the narrower the angle. For chord length, T1 was the
      shortest at 46.9 mm and T8 was the longest at 60.1 mm. CONCLUSION: When
      transpedicular screw fixations carried out at the mid-thoracic level, special
      care must be taken because there is a high chance of danger of medial wall
      violation. In these circumstances, extrapedicular screw fixation may be
      considered as an alternative treatment.

PMID- 19844614
TI  - Anterior prefrontal involvement in implicit contextual change detection.
AB  - Anterior prefrontal cortex is usually associated with high level executive
      functions. Here, we show that the frontal pole, specifically left lateral
      frontopolar cortex, is involved in signaling change in implicitly learned spatial
      contexts, in the absence of conscious change detection. In a variant of the
      contextual cueing paradigm, participants first learned contingencies between
      distractor contexts and target locations implicitly. After learning, repeated
      distractor contexts were paired with new target locations. Left lateral
      frontopolar [Brodmann area (BA) 10] and superior frontal (BA9) cortices showed
      selective signal increase for this target location change in repeated displays in
      an event-related fMRI experiment, which was most pronounced in participants with
      high contextual facilitation before the change. The data support the view that
      left lateral frontopolar cortex is involved in signaling contextual change to
      posterior brain areas as a precondition for adaptive changes of attentional
      resource allocation. This signaling occurs in the absence of awareness of learned
      contingencies or contextual change.

PMID- 19844616
TI  - Thoracic myelopathy caused by ossification of the ligamentum flavum.
AB  - OBJECTIVE: Ossification of the ligamentum flavum (OLF) is a rare cause of
      thoracic myelopathy. The aim of this study was to identify factors associated
      with the surgical outcome on the basis of preoperative clinical and radiological
      findings. METHODS: Data obtained in 26 patients whot underwent posterior
      decompression for thoracic myelopathy, caused by thoracic OLF, were analyzed
      retrospectively. Patient age, duration of symptoms, OLF type, preoperative and
      postoperative neurological status using the Japanese Orthopedic Association (JOA)
      scoring system, surgical outcome, and other factors were reviewed. We compared
      the various factors and postoperative prognosis. All patients had undergone
      decompressive laminectomy and excision of the OLF. RESULTS: Using the JOA score,
      the functional improvement was excellent in 8 patients, good in 14, fair in 2,
      and unchanged in 2. A mean preoperative JOA score of 6.65 improved to 8.17 after
      an average of 27.3 months. According to our analysis, age, gender, duration of
      symptoms, the involved spinal level, coexisting spinal disorders, associated
      trauma, intramedullary signal change, and dural adhesions were not related to the
      surgical outcome. However, the preoperative JOA score and type of OLF were the
      most important predictors of the surgical outcome. CONCLUSION: Early diagnosis
      and sufficient surgical decompression could improve the functional prognosis for
      thoracic OLF. The postoperative results were found to be significantly associated
      with the preoperative severity of myelopathy and type of OLF.

PMID- 19844617
TI  - Medpor Craniotomy Gap Wedge Designed to Fill Small Bone Defects along Cranial
      Bone Flap.
AB  - OBJECTIVE: Medpor porous polyethylene was used to reconstruct small bone defects
      (gaps and burr holes) along a craniotomy bone flap. The feasibility and cosmetic
      results were evaluated. METHODS: Medpor Craniotomy Gap Wedges, V and T, were
      designed. The V implant is a 10 cm-long wedge strip, the cross section of which
      is an isosceles triangle with a 4 mm-long base, making it suitable for gaps less
      than 4 mm after trimming. Meanwhile, the Medpor T wedge includes a 10 mm-wide
      thin plate on the top surface of the Medpor V Wedge, making it suitable for gaps
      wider than 4 mm and burr holes. Sixty-eight pterional craniotomies and 39
      superciliary approaches were performed using the implants, and the operative
      results were evaluated with respect to the cosmetic results and pain or
      tenderness related to the cranial flap. RESULTS: The small bone defects were
      eliminated with less than 10 minutes additional operative time. In a physical
      examination, there were no considerable cosmetic problems regarding to the
      cranial bone defects, such as a linear depression or dimple in the forehead,
      anterior temporal hollow, preauricular depression, and parietal burr hole defect.
      Plus, no patient suffered from any infectious complications. CONCLUSION: The
      Medpor Craniotomy Gap Wedge is technically easy to work with for reconstructing
      small bone defects, such as the bone gaps and burr holes created by a craniotomy,
      and produces excellent cosmetic results.

PMID- 19844618
TI  - Pressure measurement in carpal tunnel syndrome : correlation with
      electrodiagnostic and ultrasonographic findings.
AB  - OBJECTIVE: This study was done to evaluate the correlation between carpal tunnel
      pressure (CTP), electrodiagnostic and ultrasonographic findings in patients with
      carpal tunnel syndrome (CTS). METHODS: CTP was measured during endoscopic carpal
      tunnel release (ECTR) for CTS using Spiegelberg ICP monitoring device with
      parenchymal type catheter. Neurophysiologic severity and nerve cross sectional
      area were evaluated using nerve conductive study and ultrasonography (USG) before
      ECTR in all patients. RESULTS: Tests were performed in a total of 48 wrists in 39
      patients (9 cases bilateral). Maximum CTP was 56.7 +/- 19.3 mmHg (Mean +/- SD)
      and 7.4 +/- 3.3 mmHg before and after ECTR, respectively. No correlation was
      found between maximum CTP and either neurophysiologic severity or nerve cross
      sectional area, whereas we found a significant correlation between the latter two
      parameters. CONCLUSION: CTP was not correlated with neurophysiologic severity and
      nerve cross sectional area. Dynamic, rather than static, pressure in carpal
      tunnel might account for the basic pathophysiology of CTS better.

PMID- 19844619
TI  - Time to recover consciousness in patients with diffuse axonal injury : assessment
      with reference to magnetic resonance grading.
AB  - OBJECTIVE: This study was conducted to investigate the correlation between the
      degrees of injury on brain magnetic resonance imaging (MRI) and the time interval
      to recovery of consciousness in patients with diffuse axonal injury. METHODS:
      From January 2004 to December 2008, 25 patients with diffuse axonal injury were
      treated at our hospital. We retrospectively investigated the patients' medical
      records and radiological findings. We divided the patients into three groups
      according to the grade of MRI finding : grade I, small scattered lesions on the
      white matter of the cerebral hemisphere; grade II, focal lesions on the corpus
      callosum; and grade III, additional focal lesions on the brain stem. RESULT:
      Seven patients belonged to the grade I group; 10 to the grade II group; and 8 to
      the grade III group. The mean Glasgow Coma Scale (GCS) score of all patients at
      the time of admission was 7.28. Recovery of consciousness was observed in 23 of
      the 25 patients; the remaining two patients never regained consciousness. The
      time interval to recovery of consciousness (awake status) ranged from 1 day to
      125 days (mean 22.1 days) : grade I group patients, within approximately 1 week
      (mean 3.7 days); grade II group patients, within approximately 2 weeks (mean 12.5
      days); and grade III group patients, within approximately 2 months (mean 59.5
      days). CONCLUSION: Our study results suggest a correlation between the mean time
      interval to recovery of consciousness in patients with diffuse axonal injuries
      and the degrees of brain injuries seen on MRI. Patients with grade I and II
      diffuse axonal injuries recovered consciousness within 2 weeks, while patients
      with grade III injuries required approximately 2 months.

PMID- 19844620
TI  - Chronic subdural hematomas : a comparative study of three types of operative
      procedures.
AB  - OBJECTIVE: Several surgical procedures have been reported for the treatment of
      chronic subdural hematoma (CSDH). We compared the results of treatments for CSDH
      obtained from one burr-hole craniostomy with closed system drainage with or
      without irrigation, two burr-hole craniostomy with closed system drainage with
      irrigation, and small craniotomy with irrigation and closed-system drainage.
      METHODS: Eighty-seven patients with CSDH underwent surgery at our institution
      from January 2004 to December 2008. Our patients were classified into three
      groups according to the operative procedure; group I, one burr-hole craniostomy
      with closed system drainage with or without irrigation (n = 25), group II, two
      burr-hole craniostomy with closed system drainage with irrigation (n = 32), and
      group III, small craniotomy with irrigation and closed-system drainage (n = 30).
      RESULTS: Age distribution, male and female ratio, Markwalder's grade on admission
      and at the time of discharge, size of hematoma before and after surgery, duration
      of operation, Hounsfield unit of hematoma before and after surgery, duration of
      hospital treatment, complication rate, and revision rate were categories that we
      compared between groups. Duration of operation and hospitalization were only two
      categories which were different. But, when comparing burr hole craniostomy group
      (group I and group II) with small craniotomy group (group III), duration of post
      operative hospital treatment, complication and recurrence rate were statistically
      lower in small craniotomy group, even though operation time was longer.
      CONCLUSION: Such results indicate that small craniotomy with irrigation and
      closed-system drainage can be considered as one of the treatment options in
      patients with CSDH.

PMID- 19844621
TI  - Brain Injuries during Intraoperative Ventriculostomy in the Aneurysmal
      Subarachnoid Hemorrhage Patients.
AB  - OBJECTIVE: Intraoperative ventriculostomy is widely adopted to make the slack
      brain. However, there are few reports about hemorrhagic or parenchymal injuries
      after ventriculostomy. We tried to analyze and investigate the incidence of these
      complications in a consecutive series of patients with aneurysmal subarachnoid
      hemorrhage (SAH). METHODS: From September 2006 to June 2007, 43 patients
      underwent surgical clipping for aneurysmal SAH at our hospital. Among 43
      patients, we investigated hemorrhagic or parenchymal injuries after
      intraoperative ventriculostomy using postoperative computed tomographic scan in
      26 patients. After standard pterional craniotomy, ventriculostomy catheter was
      inserted perpendicular to the cortical surface along the bisectional imaginary
      line from Paine's point. RESULTS: Hemorrhagic injuries were detected in 12 of 26
      patients (46.2%). Mean systolic blood pressure during anesthesia was with in
      statistically significant parameter related to hemorrhage (p = 0.006). On the
      other hand, parenchymal injuries were detected in 11 of 26 patients (42.3%).
      Female and the amount of infused mannitol during anesthesia showed statistically
      significant parameters related to parenchymal injury (p = 0.005, 0.04,
      respectively). However, there were no ventriculostomy-related severe
      complications. CONCLUSION: In our series, hemorrhagic or parenchymal injuries
      after intraoperative ventriculostomy occurred more commonly than previously
      reported series in aneurysmal SAH patients. Although the clinical outcomes of
      complications are generally favorable, neurosurgeon must keep in mind the
      frequent occurrence of brain injury after intraoperative ventriculostomy in the
      acute stage of aneurysmal SAH.

PMID- 19844622
TI  - Detachable coil embolization for saccular posterior inferior cerebellar artery
      aneurysms.
AB  - OBJECTIVE: Surgical treatment of posterior inferior cerebellar artery (PICA)
      aneurysms is challenging due to limited surgical accessibility. Endovascular
      approach has a benefit of avoiding direct injury to the brainstem or lower
      cranial nerves. Therefore, it has recently been considered an alternative or
      primary modality for PICA aneurysms. We retrospectively assessed outcomes
      following detachable coil embolization of saccular PICA aneurysms. METHODS: From
      February 1997 to December 2007, we performed endovascular procedures to treat 15
      patients with 15 PICA aneurysms. Fourteen patients with 14 PICA aneurysms
      morphology of which was saccular were reviewed retrospectively. Twelve patients
      had ruptured aneurysms. The aneurysms arose from the PICA origin site (n = 12),
      the PICA lateral medullary segment (n = 1), or the PICA tonsilomedullary segment
      (n = 1). RESULTS: Complete aneurysm occlusion was achieved in 10 patients,
      residual neck in 3, and residual sac in one. Radiological follow-up was performed
      in 7 patients with mean duration of 34.7 months (range, 1-97 months) and showed
      stable or complete occlusion in 6 patients. There were no rebleeding or
      retreatment after endovascular treatment. Thromboembolism was the only procedure
      related complication (n = 4 ; 28.6%). Asymptomatic PICA infarction occurred in
      two patients and symptomatic PICA infarction in two elderly patients with poor
      clinical grade. Of these procedural PICA infarction cases, 1 symptomatic PICA
      infarction patient developed ventriculitis and septic shock leading to death. The
      clinical outcome was good in 10 patients (71.4%). CONCLUSIONS: In the present
      study, detachable coil embolization has shown as an efficient modality for PICA
      saccular aneurysms challenging indications of microsurgery. However,
      thromboembolic complications should be considered, especially in poor clinical
      elderly patients with ruptured aneurysms.

PMID- 19844623
TI  - Types of thromboembolic complications in coil embolization for intracerebral
      aneurysms and management.
AB  - OBJECTIVE: We describe our clinical experiences and outcomes in patients who had
      thromboembolic complications occurring during endovascular treatment of
      intracerebral aneurysms with a review of the literature. The types of
      thromboembolic complications were divided and the treatment modalities for each
      type were described. METHODS: Between August 2004 and March 2009 we performed
      endovascular embolization with Guglielmi detachable coils for 173 patients with
      189 cerebral aneurysms, including ruptured and unruptured aneurysms at our
      hospital. Sixty-eight patients were males and 105 patients were females. The age
      of patients ranged from 22-82 years (average, 58.8 years). We retrospectively
      evaluated this group with regard to complication rates and outcomes. The types of
      thromboembolic complications were classified into the following three categories:
      mechanical obstruction, distal embolic stroke, and stent-induced complications,
      which corresponded to types I, II, and III, respectively. A comparison of the
      clinical results was made for each type of complication. RESULTS: Only eight
      patients had a thromboembolic complication during or after a procedure (4.6%). Of
      the eight patients, two had a mechanical obstruction as the causative factor; the
      other three patients had distal embolic stroke as the causative factor. The
      remaining three patients had stent-induced complications. In cases of mechanical
      obstruction, recanalization occurred due to the use of intra-arterial
      thrombolytic agents in one of two patients. Nevertheless, a poor prognosis was
      seen. In the cases of stent-induced complications, in one of three patients in
      whom a thrombus developed following stent insertion, a middle cerebral artery
      territory infarct developed with a poor prognosis despite the use of wiring and
      an intra-arterial thrombolytic agent. In the cases of distal embolic stroke, all
      three patients achieved good results following the use of antiplatelet agents.
      CONCLUSION: Treatment for thromboemboic complications due to mechanical
      obstruction and stent-induced complications include antiplatelet and intra
      arterial thrombolytic agents; however, this cannot guarantee a sufficient extent
      of effectiveness. Therefore, active treatments, such as balloon angioplasty,
      stent insertion, and clot extraction, are helpful.

PMID- 19844624
TI  - Anterior communicating artery aneurysm related to visual symptoms.
AB  - OBJECTIVE: Intracranial aneurysms are sometimes presented with visual symptoms by
      their rupture or direct compression of the optic nerve. It is because their
      prevalent sites are anatomically located close to the optic pathway. Anterior
      communicating artery is especially located in close proximity to optic nerve.
      Aneurysm arising in this area can produce visual symptoms according to their
      direction while the size is small. Clinical importance of visual symptoms
      presented by aneurysmal optic nerve compression is stressed in this study.
      METHODS: Retrospective analysis of ruptured anterior communicating artery
      aneurysms compressing optic apparatus were carried out. Total 33 cases were
      enrolled in this study. Optic nerve compression of the aneurysms was confirmed by
      the surgical fields. RESULTS: In 33 cases among 351 cases of ruptured anterior
      communicating artery aneurysms treated surgically, from 1991 to 2000, the dome of
      aneurysm was compressed in optic pathway. In some cases, aneurysm impacted into
      the optic nerve that deep hollowness was found when the aneurysm sac was removed
      during operation. Among 33 cases, 10 cases presented with preoperative visual
      symptoms, such as visual dimness (5), unilateral visual field defect (2) or
      unilateral visual loss (3), 20 cases had no visual symptoms. Visual symptoms
      could not be checked in 3 cases due to the poor mental state. In 6 cases among 20
      cases having no visual symptoms, optic nerve was deeply compressed by the dome of
      aneurysm which was seen in the surgical field. Of 10 patients who had visual
      symptoms, 8 showed improvement in visual symptoms within 6 months after clipping
      of aneurysms. In 2 cases, the visual symptoms did not recover. CONCLUSION:
      Anterior communicating artery aneurysm can cause visual symptoms by compressing
      the optic nerve or direct rupture to the optic nerve with focal hematoma
      formation. We emphasize that cerebral vascular study is highly recommended to
      detect intracranial aneurysm before its rupture in the case of normal CT findings
      with visual symptoms and frequent headache.

PMID- 19844625
TI  - Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after
      aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Cerebral vasospasm leading to cerebral ischemic infarction is a major
      cause of morbidity and mortality in the patients who suffer with aneurysmal
      subarachnoid hemorrhage. Despite adequate treatment, some patients deteriorate
      and they develop symptomatic vasospasm. The objective of the present study was to
      investigate the efficacy and clinical outcome of intraarterial nimodipine
      infusion on symptomatic vasospasm that is refractory to hemodynamic therapy.
      METHODS: We retrospectively reviewed the procedure reports, the clinical charts
      and the transcranial doppler, computed tomography and digital subtraction
      angiography results for the patients who underwent endovascular treatment for
      symptomatic cerebral vasospasm due to aneurysmal SAH. During the 36 months
      between Jan. 2005 and Dec. 2007, 19 patients were identified who had undergone a
      total of 53 procedures. We assessed the difference in the arterial vessel
      diameter, the blood flow velocity and the clinical outcome before and after these
      procedures. RESULTS: Vascular dilatation was observed in 42 of 53 procedures. The
      velocities of the affected vessels before and after procedures were available in
      33 of 53 procedures. Twenty-nine procedures exhibited a mean decrease of 84.1
      cm/s. We observed clinical improvement and an improved level of consciousness
      with an improved GCS score after 23 procedures. CONCLUSION: Based on our results,
      the use of intraarterial nimodipine is effective and safe in selected cases of
      vasospasm following aneurysmal SAH. Prospective, randomized studies are needed to
      confirm these results.

PMID- 19844626
TI  - Clinical analysis of novalis stereotactic radiosurgery for brain metastases.
AB  - OBJECTIVE: The authors analyzed the effectiveness and therapeutic response of
      Novalis shaped beam radiosurgery for metastatic brain tumors, and the prognostic
      factors which influenced the outcome. METHODS: We performed a retrospective
      analysis of 106 patients who underwent 159 treatments for 640 metastatic brain
      lesions between January 2000 and April 2008. The pathologies of the primary tumor
      were mainly lung (45.3%), breast (18.2%) and GI tract (13.2%). We classified the
      patients using Radiation Therapy Oncology Group Recursive Partitioning Analysis
      (RPA) and then analyzed the survival and prognostic factors according to the
      Kaplan Meier method and univariate analysis. RESULTS: The overall median
      actuarial survival rate was 7.3 months from the time of first radiosurgery
      treatment while 1 and 2 year actuarial survival estimates were 31% and 14.4%,
      respectively. Median actuarial survival rates for RPA classes I, II, and III were
      31.3 months, 7.5 months and 1.7 months, respectively. Patients' life spans,
      higher Karnofsky performance scores and age correlated closely with RPA classes.
      However, sex and the number of lesions were not found to be significantly
      associated with length of survival. CONCLUSION: This result suggests that Novalis
      radiosurgery can be a good treatment option for treatment of the patients with
      brain metastases.

PMID- 19844627
TI  - A case of infantile meningioangiomatosis with a separate cyst.
AB  - Meningioangiomatosis (MA) is a rare congenital tumor that occurs mostly in 5-15
      year old children. There have been only 5 cases previously reported that
      described the cystic nature within these tumors. We present a case of a MA
      accompanied by a separate macrocyst. A normally developed 2 year-old female
      patient presented with partial and generalized seizures. The brain computerized
      tomogram and magnetic resonance imaging revealed the presence of a calcified mass
      accompanied by a cyst in the right parietal area, surrounded by low density and
      high attenuation edema and hemorrhage. Upon right parietal craniotomy, a 1.6 cm x
      1.2 cm x 0.5 cm sized plate-like, gray-white, slightly hard mass was seen and it
      was completely excised. Approximately 1 cm from the mass in the anterior lateral
      direction, a cyst was found and subsequent biopsy of the cyst wall revealed no
      tumor tissue, and therefore the cyst was not removed. Pathologic report
      demonstrated the meningioangiomatosis. Follow up examination 2 years later showed
      no recurrence of the tumor, and there was no evidence of neurological deficits.
      Authors suggest that cysts that arise in the surrounding tissues of tumors may
      not be tumor cysts, and do not require surgical removal.

PMID- 19844628
TI  - Intraventricular hemorrhage long after successful encephaloduroarterio
      synangiosis in moyamoya patient.
AB  - Intraventricular hemorrhage long after successful encephaloduroarterio
      synangiosis (EDAS) is very rare. The effect of revascularization surgery for
      preventing hemorrhagic event of moyamoya disease remains controversial. We report
      a 17-year-old female with intracerebral hemorrhage and intraventricular
      hemorrahge 10 years after successful EDAS. Even though cerebral vessels
      angiography showed good collateral circulations without specific weak points, a
      cerebral hemorrhage could occur in patient with ischemic type of moyamoya disease
      long after successful indirect bypass operations. Good collateralization of
      cerebral angiography or magnetic resonance perfusion image after indirect bypass
      surgery would ensure against ischemic symptoms, not a hemorrhage. And, thus a
      life-time follow-up strategy might be necessary even if a good collateral
      circulation has been established.

PMID- 19844629
TI  - Endovascular treatment for common iliac artery injury complicating lumbar disc
      surgery : limited usefulness of temporary balloon occlusion.
AB  - Vascular injury during lumbar disc surgery is a rare but potentially life
      threatening complication. It has been managed by open vascular surgical repair.
      With recent technologic advance, endovascular treatment became one of effective
      treatment modalities. We present a case of a 32-year-old woman who suffered with
      common iliac artery injury during lumbar disc surgery that was treated
      successfully by endovascular repair with temporary balloon occlusion and
      subsequent insertion of a covered stent. Temporary balloon occlusion for 1.5
      hours could stop bleeding, but growing pseudoaneurysm was identified at the
      injury site during the following 13 days. It seems that the temporary balloon
      occlusion can stall bleeding from arterial injury for considerable time duration,
      but cannot be a single treatment modality and requires subsequent insertion of a
      covered stent.

PMID- 19844630
TI  - Dynamic lumbar spinal stenosis : the usefulness of axial loaded MRI in
      preoperative evaluation.
AB  - Two cases of dynamic lumbar spinal stenosis were identified by the authors using
      axial loaded magnetic resonance image (MRI). In both cases, the patients
      presented with neurogenic claudication but MRI in decumbency showed no definite
      pathologic condition associated with their symptoms. In contrast, axial loaded
      MRI demonstrated constrictive spinal stenosis and a significantly decreased dural
      sac caused by epidural fat buckling and thickening of the ligamentum flavum in
      both cases. In the second case, a more prominent disc protrusion was also
      demonstrated compared with decumbent MRI. After decompressive surgery, both
      patients had satisfactory outcomes. Axial loaded MRI can therefore give decisive
      information in dynamic spinal disorders by allowing simulation of an upright
      position.

PMID- 19844631
TI  - Hemifacial spasm caused by a huge tentorial meningioma.
AB  - A rare case of hemifacial spasm caused by an ipsilateral tentorial meningioma is
      described. Magnetic resonance imaging showed a huge tumor in the right cerebellar
      hemisphere, distant to the cerebello-pontine cistern. The facial
      vestibulocochlear nerve complex was stretched by the shift of the brainstem and
      the right cerebello-pontine cistern was effaced. After removing the tumor, the
      hemifacial spasm resolved completely. We review our case with the pertinent
      literature regarding the etiological mechanism.

PMID- 19844632
TI  - Median Nerve Stimulation in a Patient with Complex Regional Pain Syndrome Type
      II.
AB  - A 54-year-old man experienced injury to the second finger of his left hand due to
      damage from a paintball gun shot 8 years prior, and the metacarpo-phalangeal
      joint was amputated. He gradually developed mechanical allodynia and burning
      pain, and there were trophic changes of the thenar muscle and he reported
      coldness on his left hand and forearm. A neuroma was found on the left second
      common digital nerve and was removed, but his symptoms continued despite various
      conservative treatments including a morphine infusion pump on his left arm. We
      therefore attempted median nerve stimulation to treat the chronic pain. The
      procedure was performed in two stages. The first procedure involved exposure of
      the median nerve on the mid-humerus level and placing of the electrode. The trial
      stimulation lasted for 7 days and the patient's symptoms improved. The second
      procedure involved implantation of a pulse generator on the left subclavian area.
      The mechanical allodynia and pain relief score, based on the visual analogue
      scale, decreased from 9 before surgery to 4 after surgery. The patient's activity
      improved markedly, but trophic changes and vasomotor symptom recovered only
      moderately. In conclusion, median nerve stimulation can improve chronic pain from
      complex regional pain syndrome type II.

PMID- 19844633
TI  - Traumatic acute subdural hematoma extending from the posterior cranial fossa to
      the cerebellopontine angle.
AB  - Posterior cranial fossa subdural hematomas and extension of the subdural hematoma
      to the cerebellopontine angle is rarely seen and the concurrent development of
      acute peripheral facial palsy and the management strategy have not previously
      been reported in this pathology because of its rarity. We present this case to
      emphasize that minor head trauma may lead to a posterior cranial fossa hematoma
      extending to the cerebellopontine angle and cause peripheral facial palsy in
      patients using aspirin (acetylsalicylic acid). In addition, partial evacuation
      and waiting for the resorption of the hematoma may help to prevent damage to the
      7th and 8th cranial nerves.

PMID- 19844638
TI  - The impact of genomics on the exploitation of the myxobacterial secondary
      metabolome.

PMID- 19844639
TI  - Genomics of secondary metabolite production by Pseudomonas spp.

PMID- 19844640
TI  - Mining cyanobacterial genomes for genes encoding complex biosynthetic pathways.

PMID- 19844637
TI  - Genomic basis for natural product biosynthetic diversity in the actinomycetes.

PMID- 19844641
TI  - Functional genomics for plant natural product biosynthesis.

PMID- 19844645
TI  - Who are the restrained and secluded patients: a 15-year nationwide study.
AB  - BACKGROUND: To find interventions for reducing the use of restraint and
      seclusion, it is necessary to identify who the restrained and secluded patients
      are. The aim of the present study was to determine which demographic and clinical
      groups of psychiatric inpatients are at risk of being restrained/secluded, and
      whether there have been changes in the restrained/secluded patients' profiles
      over a 15-year period in Finland. METHOD: A structured postal survey concerning
      the demographic and clinical information of restrained/secluded patients was
      completed in all Finnish psychiatric hospitals during a predetermined week in
      1990, 1991, 1994, 1998, and 2004. The National Hospital Discharge Register was
      used to gather information on all psychiatric inpatients during the study weeks.
      RESULTS: Out of the variables studied (age, gender, main diagnosis, phase of
      hospital stay), only the main diagnosis and the phase of hospital stay were
      independent risk factors for restraint/seclusion, and remained constant over
      time. The age profile of the restrained/secluded patients was unstable over time
      and the risk of being restrained/secluded was not associated with gender.
      CONCLUSION: Restraint and seclusion is used mainly among the acute and the most
      disturbed patients. Therefore, in order to reduce the use of restraint and
      seclusion, resources should be targeted especially to these groups.

PMID- 19844646
TI  - Glucocorticoid-induced osteoporosis in growing mice is not prevented by
      simultaneous intermittent PTH treatment.
AB  - Glucocorticoids (GCs) are widely used in medicine for treatment of chronic
      diseases. Especially in children, prolonged treatment causes growth retardation
      and early onset of osteoporosis. Human parathyroid hormone (PTH) has an anabolic
      effect on bone when administrated intermittently. The aim of the present study
      was to examine whether a combined therapy of dexamethasone (DEX) and PTH could
      prevent the detrimental effects of GC on cortical and trabecular bone in the
      femur and vertebrae of growing mice. Three-week-old female FVB mice were treated
      with control, DEX, PTH, or a combination of DEX and PTH by daily subcutaneous
      injections. After 4 weeks, animals were killed and the femur and L5 vertebra were
      isolated. Cortical and trabecular bone parameters and relative calcium density
      were measured by high-resolution X-ray micro-computed tomography (micro-CT). In
      the femur, PTH can reverse the effects of DEX on bone volume to control. However,
      it cannot reverse the undermineralization, which most likely is a strong
      contributor to bone fragility. In the vertebra, PTH improves bone volume to some
      extent but does not restore the values to normal. It augments the negative effect
      of DEX on mineralization. We conclude that the detrimental effects of DEX in the
      growing skeleton cannot be prevented by simultaneous PTH treatment.

PMID- 19844642
TI  - Metagenomic approaches to natural products from free-living and symbiotic
      organisms.

PMID- 19844647
TI  - Resolution of phenotypically distinct strains of Enterococcus spp. in a complex
      microbial community using cpn60 universal target sequencing.
AB  - Characterization of complex microbial communities is frequently based on the
      examination of polymerase chain reaction amplified sequences from a single
      phylogenetic marker, usually the 16S rRNA gene. However, this commonly used
      target often does not offer robust resolution of species or sub-species and is
      thus not a sufficiently informative target for understanding microbial population
      dynamics occurring at the strain level. We have used the cpn60 universal target
      sequence to characterize Enterococcus isolates from feces of growing pigs and
      have shown that sub-species groups, not detected using 16S rRNA sequences, can be
      resolved. Furthermore, groups resolved by cpn60-based phylogenetic analysis have
      distinct phenotypes. We report changes in the structure and function of
      Enterococcus communities in pig feces sampled from individual animals at three
      times, from suckling through to maturity. Enterococcus faecalis was largely
      replaced by Enterococcus hirae between suckling and 9 weeks of age, and a shift
      from one sub-species group of E. hirae to another was observed in all animals
      between 9 and 15 weeks. Conversely, E. faecalis strains remained consistent
      throughout the study period. Our results demonstrate that cpn60 sequences can be
      used to detect strain level changes in Enterococcus populations during succession
      in the fecal microbiota of growing pigs.

PMID- 19844648
TI  - Sialic acid-containing lipopolysaccharides of Salmonella O48 strains--potential
      role in camouflage and susceptibility to the bactericidal effect of normal human
      serum.
AB  - Sialic acid (N-acetylneuraminic acid, NeuAc) plays an essential role in
      protecting gram-negative bacteria against the bactericidal activity of serum and
      may contribute to the pathogenicity of bacteria by mimicking epitopes that
      resemble host tissue components (molecular mimicry). The role of sialic acid
      (NeuAc)-containing lipopolysaccharides (LPS) of Salmonella O48 strains in the
      complement activation of normal human serum (NHS) was investigated. NeuAc
      containing lipooligosaccharides cause a downregulation of complement activation
      and may serve to camouflage the bacterial surface from the immunological response
      of the host. Serotype O48 Salmonella strains have the O-antigen structure
      containing NeuAc while its serovars differ in outer membrane protein composition.
      In this study, the mechanisms of complement activation responsible for killing
      Salmonella O48 serum-sensitive rods by NHS were established. Four of such
      mechanisms involving pathways, which are important in the bactericidal mechanism
      of complement activation, were distinguished: only the classical/lectin pathways,
      independent activation of the classical/lectin or alternative pathway, parallel
      activation of the classical/lectin and alternative pathways, and only the
      alternative pathway important in the bactericidal action of human serum. To
      further study the role of NeuAc, its content in bacterial cells was determined by
      gas-liquid chromatography-mass spectrometry in relation to 3-deoxy-D-manno-2
      octulosonic acid (Kdo), an inherent constituent of LPS. The results indicate that
      neither the presence of sialic acid in LPS nor the length of the O-specific part
      of LPS containing NeuAc plays a decisive role in determining bacterial resistance
      to the bactericidal activity of complement and that the presence of sialic acid
      in the structure of LPS is not sufficient to block the activation of the
      alternative pathway of complement. We observed that for three strains with a very
      high NeuAc/Kdo ratio the alternative pathways were decisive in the bactericidal
      action of human serum. The results indicated that those strains are not capable
      of inhibiting the alternative pathway very effectively. As the pathogenicity of
      most Salmonella serotypes remains undefined, research into the interactions
      between these bacterial cells and host organisms is indispensable.

PMID- 19844649
TI  - In vitro and in vivo evaluation of the prebiotics GroBiotic-A, inulin,
      mannanoligosaccharide, and galactooligosaccharide on the digestive microbiota and
      performance of hybrid striped bass (Morone chrysops x Morone saxatilis).
AB  - Two separate experiments were conducted with hybrid striped bass to evaluate four
      potential prebiotics: GroBiotic-A (partially autolyzed brewer's yeast, dairy
      ingredient components, and fermentation products), mannanoligosaccharide (MOS),
      galactooligosaccharide (GOS), and inulin. In the in vitro experiment, intestinal
      contents were incubated with the individual prebiotics (0.5% by weight) at 25
      degrees C for 24 and 48 h. Analysis of volatile fatty acids in the supernatant
      showed that GroBiotic-A, MOS, and GOS tended to produce lower acetate levels but
      higher butyrate levels at 48 h compared to diet alone. However, denaturing
      gradient gel electrophoresis (DGGE) analysis failed to detect any differences in
      the composition of the microbial community among treatments. DNA sequencing of a
      common band for all inoculated samples revealed close similarity to the anaerobic
      Fusobacteria bacterium. An 8-week feeding trial also was conducted to evaluate
      the four prebiotics looking at growth performance; weight gain, feed efficiency
      ratio, protein efficiency ratio, whole-body ash, moisture, and lipid did not vary
      among fish fed the various diets. However, DGGE analysis revealed that all
      prebiotics produced a different type of microbial community in the intestinal
      tract of hybrid striped bass compared to fish fed the basal diet. Thus, GroBiotic
      A, FOS, GOS, and MOS exhibited prebiotic effects in hybrid striped bass.

PMID- 19844650
TI  - Microbial protein in soil: influence of extraction method and C amendment on
      extraction and recovery.
AB  - The capacity to study the content and resolve the dynamics of the proteome of
      diverse microbial communities would help to revolutionize the way microbiologists
      study the function and activity of microorganisms in soil. To better understand
      the limitations of a proteomic approach to studying soil microbial communities,
      we characterized extractable soil microbial proteins using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Two methods were utilized to
      extract proteins from microorganisms residing in a Quitman and Benfield soil: (1)
      direct extraction of bulk protein from soil and (2) separation of the
      microorganisms from soil using density gradient centrifugation and subsequent
      extraction (DGC-EXT) of microbial protein. In addition, glucose and toluene
      amendments to soil were used to stimulate the growth of a subset of the microbial
      community. A bacterial culture and bovine serum albumin (BSA) were added to the
      soil to qualitatively assess their recovery following extraction. Direct
      extraction and resolution of microbial proteins using SDS-PAGE generally resulted
      in smeared and unresolved banding patterns on gels. DGC-EXT of microbial protein
      from soil followed by separation using SDS-PAGE, however, did resolve six to 10
      bands in the Benfield but not the Quitman soil. DGC-EXT of microbial protein, but
      not direct extraction following the addition of glucose and toluene, markedly
      increased the number of bands (approximately 40) on the gels in both Benfield and
      Quitman soils. Low recoveries of added culture and BSA proteins using the direct
      extraction method suggest that proteins either bind to soil organic matter and
      mineral particles or that partial degradation takes place during extraction.
      Interestingly, DGC may have been preferentially selected for actively growing
      cells, as gauged by the 10-100x lower cy19:0/18:1omega7 ratio of the fatty acid
      methyl esters in the isolated community compared to that for the whole soil. DGC
      can be used to isolate soil communities and provide microbial protein that can be
      characterized using PAGE.

PMID- 19844651
TI  - The fascial structures of the rectum and the "so-called mesorectum": an
      anatomical or a terminological controversy?

PMID- 19844652
TI  - Intraoperative fluorescent imaging using indocyanine green for liver mapping and
      cholangiography.
AB  - BACKGROUND: Preoperative imaging is widely used and extremely helpful in
      hepatobiliary surgery. However, transfer of preoperative data to a intraoperative
      situation is very difficult. Surgeons need intraoperative anatomical information
      using imaging data for safe and precise operation in the field of hepatobiliary
      surgery. We have developed a new system for mapping liver segments and
      cholangiograms using intraoperative indocyanine green (ICG) fluorescence under
      infrared light observation. METHOD: The imaging technique for mapping liver
      segments and cholangiogram based on ICG fluorescence used an infrared-based
      navigation system. Eighty one patients with liver tumors underwent hepatectomy
      from 2006, January to 2009, March. In liver surgery, 1 ml of ICG was injected via
      the portal vein under observation by the fluorescent imaging system. Fourteen
      patients were underwent laparoscopic cholecystectomy for chronic cholecystitis
      with gallstones. In laparoscopic cholecystectomy, 5 ml of ICG was administered
      intravenously just before operation and the bile duct was observed using the
      infrared-based navigation system. RESULT: This new technique successfully
      identified stained subsegments and segments of the liver in 73 of 81 patients
      (90.1%). Moreover, clear mapping of liver segments was obtained even against a
      background of liver cirrhosis. Fluorescent cholangiography clearly showed the
      common bile duct and cystic duct in 10 of 14 patients (71.4%). No adverse
      reactions to the ICG were encountered. CONCLUSION: Application of this technique
      allows intraoperative identification of anatomical landmark in hepatobiliary
      surgery.

PMID- 19844653
TI  - Is pancreatectomy with arterial reconstruction a safe and useful procedure for
      locally advanced pancreatic cancer?
AB  - BACKGROUND/PURPOSE: We often encounter unresectable pancreatic cancer due to
      invasions of the major vessels. Vascular resection for locally advanced
      pancreatic cancers has an advantage in en block local resection. There are
      potential cases in which good outcomes can be achieved by arterial resection.
      METHODS: Pancreatectomy (including total pancreatectomy in 15 cases,
      pancreatoduodenectomy in 7 cases and distal pancreatectomy in one case) was
      performed in 23 cases of invasive ductal carcinoma of the pancreas, in
      combination with resection and reconstruction of the hepatic artery in 15 cases,
      the superior mesenteric artery in 12 cases (there are overlaps) and the portal
      vein in 20 cases. RESULTS: The median operating time was 686 min (416-1,190 min)
      and the median blood loss was 2,830 ml (440-19,800 ml). This shows that the
      surgery was highly-invasive. The operative mortality rate was 4.3%. On the basis
      of the UICC classification, there were 2 cases of Stage IIa, 4 cases of Stage
      IIb, 9 cases of Stage III, 8 cases of Stage IV, while there were 18 cases (78.3%)
      of R0 resection. On the other hand, the final histological findings showed that
      there were 8 cases (34.8%) of M1 (liver and non-regional lymph node metastases),
      so it is thought that decisions on operative indications should be not be made
      slightly. As for the overall survival rate, the 1-year survival rate was 51.2%
      and the 3-year survival rate was 23.1% while the median survival time (MST) was
      12 months. As for 15 cases of M0, the 1-year survival rate was 61.9% and the 4
      year survival rate was 38.7% while the MST was 16 months. On the other hand, the
      MST was poor (10 months) in 8 cases of M1, showing that a statistically
      significant difference was observed depending upon the degree of metastasis (log
      rank P = 0.0409). In 18 cases of R0, the 1-year survival rate was 67.2%, the 4
      year survival rate 30.2% and the MST 13 months, respectively, while in 5 cases of
      R1 and R2, the MST was 6 months, showing that there was a statistically
      significant difference between R0 cases and R1, R2 cases (log-rank P = 0.0002).
      CONCLUSIONS: Further discussion is required concerning surgical indications and
      significance. However, it is thought that resection is useful only when surgery
      of R0 has taken place for selected locally advanced pancreatic cancer (M0).

PMID- 19844655
TI  - Spinal arthroplasty is here to stay: editorial.

PMID- 19844656
TI  - Overview of disc arthroplasty-past, present and future.
AB  - Degenerative disc disease is one of the most frequent spinal disorders. The
      anatomy and the biomechanics of the intervertebral disc are very complex, and the
      pathomechanics of its degeneration are poorly understood. Despite this complexity
      and uncertainty, great advances have been made in the field of disc replacement
      technology, with promising results. Difficulties are continuously being
      encountered, but careful analysis of the results and intensive research and
      development will assist in countering these problems. There are approximately 40
      clinical reports in the literature describing various aspects of randomised
      controlled trials involving intervertebral disc arthroplasty. However, the
      majority of these publications do not provide reliable information, in that they
      give only interim results and/or the results from just one of the many centres in
      multicentre studies. Such publications must be interpreted with caution, since
      they do not always represent the results of the whole study population and may
      hence be underpowered. We identified six randomised controlled trials that
      compared the final clinical outcomes of disc arthroplasty and spinal fusion. The
      present systematic review attempts to give an overview of the current status of
      disc arthroplasty.

PMID- 19844657
TI  - The colon in patients with ankylosing spondylitis and in normal controls in
      Bangladesh: a macroscopic and microscopic study.
AB  - The objective of this paper is to study the macroscopic and microscopic aspects
      of colonic mucosa in patients with ankylosing spondylitis (AS) and in controls
      without colonic symptoms in Bangladesh. This observational study was done in a
      tertiary care center of Dhaka. Twenty-eight consecutive cases of AS were
      included, fulfilling modified New York Criteria with pure axial form or combined
      axial and peripheral joint involvement. Ten controls were enrolled in the study
      from people in whom endoscopy of upper gastrointestinal tract (GI) tract was
      performed and who had no musculoskeletal complaints and no colonic symptoms.
      Short colonoscopy (up to 60 cm) and colonoscopic biopsy were done in all.
      Histological features were evaluated following Cuvelier grading and Rubio and
      Kock scoring system. Demographic data including age and sex were similar in the
      AS and control groups. Out of 28 patients, ten had axial and 18 combined axial
      and peripheral joint disease, mostly pauciarticular. In the AS group, macroscopic
      and microscopic lesions were found in four and 14 subjects, respectively. Out of
      22 subjects without diarrhea, seven had stage II and two had stage I changes. Six
      subjects in the AS group gave a history of diarrhea, of them three had stage I
      and two had stage II changes. In the control group, no macroscopic abnormalities
      were found. On histological examination, the mean diameter of transversely cut
      rectal glands, interglandular linear distances, number of glands per area, and
      total digital scores varied between 45-90 microm, 4.6-27 microm, 5-25, and 17-18
      respectively. In eight of the ten controls, eosinophilic infiltration was found.
      Subclinical inflammatory lesions in the colonic mucosa are common in patients
      with ankylosing spondylitis. Colonic mucosa in normal individuals does not differ
      from that found in western studies, except for the presence of frequent mild
      eosinophilic infiltration in the lamina propria.

PMID- 19844658
TI  - Extracellular matrix formation after transplantation of human embryonic stem cell
      derived cardiomyocytes.
AB  - Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for
      cardiac regeneration is hampered by the formation of fibrotic tissue around the
      grafts, preventing electrophysiological coupling. Investigating this process, we
      found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and
      fibronectin, which they bind via appropriate integrins; (2) after transplantation
      into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and
      fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type
      they encounter or secrete in vivo; (4) co-transplantation of hESC-derived
      endothelial cells and/or cardiac progenitors with hESC-CM results in the
      formation of functional capillaries; and (5) transplanted hESC-CM survive and
      mature in vivo for at least 24 weeks. These results form the basis of future
      developments aiming to reduce the adverse fibrotic reaction that currently
      complicates cell-based therapies for cardiac disease, and to provide an
      additional clue towards successful engraftment of cardiomyocytes by co
      transplanting endothelial cells.

PMID- 19844660
TI  - TNF-blockade in patients with advanced hormone refractory prostate cancer.

PMID- 19844661
TI  - Phase II trial of pyrazoloacridine (NSC#366140) in patients with metastatic
      breast cancer.
AB  - PURPOSE: Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent
      that inhibits the activity of topoisomerases 1 and 2. We conducted a phase II
      clinical study to determine the efficacy and toxicities of PZA in patients with
      metastatic breast cancer (MBC). EXPERIMENTAL DESIGN: In this phase II multicenter
      study, patients who were treated with no more than one prior chemotherapy for MBC
      were treated with 750 mg/m2 of PZA given as a 3-hour intravenous infusion every 3
      weeks. Treatment cycles were continued until disease progression or unacceptable
      toxicities. The study was designed to distinguish between a response rate of <
      15% vs > 30% (alpha = 0.10, beta = 0.10) using Simons optimal 2-stage design. At
      least 2 responses were required in the first 12 patients in the 1st stage and 6
      of 35 in the 2nd stage to recommend the agent for further study. RESULTS: Two
      patients in the first stage had a response allowing accrual to second stage. A
      total of 15 patients (out of 35 planned) were treated on the study prior to
      premature closure. Three patients had a partial response (20%) lasting 4.5-6
      months. Two patients had stable disease for 3 and 5 months. The dose limiting
      toxicity was granulocytopenia with ten patients requiring dose reduction or dose
      delay for grade 4 neutropenia. Other grade 3 and 4 toxicities include vomiting (n
      = 2), nausea (n = 2), neurotoxicity (n = 1), fatigue (n = 1), anemia (n = 1),
      dyspnea 9n = 1) and renal (n = 1). CONCLUSIONS: Pyrazoloacridine demonstrated
      modest activity in patients with metastatic breast cancer.

PMID- 19844659
TI  - Laccases: a never-ending story.
AB  - Laccases (benzenediol:oxygen oxidoreductases, EC 1.10.3.2) are blue multicopper
      oxidases that catalyze the oxidation of an array of aromatic substrates
      concomitantly with the reduction of molecular oxygen to water. In fungi, laccases
      carry out a variety of physiological roles during their life cycle. These enzymes
      are being increasingly evaluated for a variety of biotechnological applications
      due to their broad substrate range. In this review, the most recent studies on
      laccase structural features and catalytic mechanisms along with analyses of their
      expression are reported and examined with the aim of contributing to the
      discussion on their structure-function relationships. Attention has also been
      paid to the properties of enzymes endowed with unique characteristics and to
      fungal laccase multigene families and their organization.

PMID- 19844662
TI  - Efficacy of caffeic acid phenethyl ester (CAPE) in skin B16-F0 melanoma tumor
      bearing C57BL/6 mice.
AB  - In current work, we investigated the in-vitro efficacy of Caffeic acid Phenethyl
      Ester (CAPE) as an anti-melanoma agent in five melanoma cell lines B16-F0,
      B16F10, SK-MEL-28, SK-MEL-5, and MeWo and in-vivo efficacy study in skin B16-F0
      melanoma tumor model in C57BL/6 mice. The IC(50) (48 h) of CAPE in above five
      melanoma cell lines was 15 uM. CAPE (20-200 uM) led to intracellular GSH
      depletion of 16-54%, and 10-25 fold increase in Reactive Oxygen Species (ROS)
      formation in B16-F0 cells. CAPE (15-30 uM) caused 5-7 fold increase in apoptosis
      in B16-F0 cells. CAPE (10, 20 and 30 mg/Kg/day) led to tumor size growth
      inhibition by 39 +/- 33%, 54 +/- 36%, and 57 +/- 18%, respectively. The
      respective therapies led to plasma Alanine Amino Transferase (ALT) levels
      corresponding to 85 +/- 18, 107 +/- 26, 154 +/- 35 IU/L in comparison to controls
      66 +/- 14 IU/L. At corresponding doses, the lipid peroxidation levels as measured
      by malondialdehyde (MDA) formation in liver homogenates were 255 +/- 8 MUM, 304
      +/- 21 MUM, and 342 +/- 14 MUM in comparison to 208 +/- 6 MUM in controls. The
      level of MDA in kidney homogenates was 263 +/- 21 MUM, 282 +/- 18 MUM, and 350 +/
      28 MUM, respectively, in comparison to 212 +/- 8 MUM in controls. Administration
      of CAPE (10, 20, 30 mg/Kg/day) diminished free thiol contents in liver for 21 +/-
      15%, 40 +/- 17%, and 44 +/- 19% and in kidney homogenates for 25 +/- 15%, 37 +/-
      18%, and 40 +/- 22%, respectively, as compared to controls. Our study suggests
      that CAPE at 10 mg/Kg/day has significant anti-melanoma efficacy with minimal
      toxicity.

PMID- 19844664
TI  - Immobilization of Escherichia coli cells with cis-epoxysuccinate hydrolase
      activity for D(-)-tartaric acid production.
AB  - Immobilization of cis-epoxysuccinate hydrolase-containing E. coli for D(-)
      tartaric acid production was screened by various methods. The highest recovery of
      activity was obtained by entrapment in kappa-carrageenan gel. 23.6 g biomass/l
      and 43.4 g kappa-carrageenan/l were the best immobilization conditions optimized
      by response surface methodology with 83% yield (114 U/g). Cell autolysis was
      observed after immobilization. Immobilized cells showed high pH (5-10) stability,
      thermal (up to 65 degrees C) stability, conversion rate (>99.5%),
      enantioselectivity (ee > 99.6%), and were less affected by metal ions and
      surfactants compared with free cells. Conversion rate for immobilized cells
      preserved 93% after 10 repeated batches (5% for free cells).

PMID- 19844663
TI  - Reduced carriership of 4G allele of plasminogen activator inhibitor-1 4G/5G
      polymorphism in very young survivors of myocardial infarction.
AB  - There are limited and controversial data regarding the impact of 4G/5G
      polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene in the
      pathogenesis of premature myocardial infarction (MI). We explored whether 4G/5G
      polymorphism of the PAI-1 gene is associated with the development of MI <or= 35
      years of age. We recruited 201 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 140 healthy individuals matched with cases for age and sex, without
      a family history of premature coronary heart disease. 4G/5G polymorphism of PAI-1
      was tested with polymerase chain reaction and reverse hybridization. 4G allele
      carriers (4G/4G and 4G/5G genotypes) of PAI-1 were less frequent in patients than
      in controls (69.6 vs. 83.6%, P = 0.007). 4G carriership of the polymorphism of
      PAI-1 was associated with lower risk for acute MI (odds ratio 0.45, 95%
      confidence interval 0.23-0.88, P = 0.02) after adjusting for major cardiovascular
      risk factors. Patients possessing the 4G allele had higher PAI-1 plasma levels
      (32.2 +/- 25 vs. 22.2 +/- 11.3 ng/ml, P = 0.006) but lower lipoprotein(a) levels
      (10.1 [2.1-29.9] vs. 15.3 [8.2-57.1] mg/dl, P = 0.03) compared to 5G/5G
      homozygotes. Our data indicate that the 4G allele of the PAI-1 4G/5G polymorphism
      is less frequent among survivors of MI at very young age compared with matched
      controls.

PMID- 19844665
TI  - Effect of additives on the activity of tannase from Aspergillus awamori MTCC9299.
AB  - Tannase from Aspergillus awamori MTCC 9299 was purified using ammonium sulfate
      precipitation followed by ion-exchange chromatography. A purification fold of
      19.5 with 13.5% yield was obtained. Temperature of 30 degrees C and pH of 5.5
      were found optimum for tannase activity. The effects of metals and organic
      solvents on the activity of tannase were also studied. Metal ions Mg(+2), Mn(+2),
      Ca(+2), Na(+), and K(+) stimulated the tannase activity, while Cu(+2), Fe(+3),
      and Co(+2) acted as inhibitors of the enzyme. The addition of organic solvents
      like acetic acid, isoamylalcohol, chloroform, isopropyl alcohol, and ethanol
      completely inhibited the enzyme activity. However, butanol and benzene increased
      the enzyme activity.

PMID- 19844666
TI  - Photolytically generated nitric oxide inhibits caspase activity and results in
      AIF-mediated cell death.
AB  - In human skin tissue nitrite is found at relatively high concentrations and
      represents the main source for cutaneous non-enzymatic nitric oxide (NO)
      formation during UVA exposure due to photolytical decomposition. Since NO has
      been repeatedly shown to act pro- as well as anti-apoptotic we here studied the
      effects of UVA irradiation on human keratinocytes in the presence of nitrite. We
      show that UVA-induced nitrite photodecomposition effectively inactivated caspase
      activity. In parallel, we observed in human skin keratinocytes, UVA-irradiated in
      the presence of nitrite, a proteolytic processing of apoptosis-inducing factor
      (AIF) followed by translocation from the mitochondrion into the nucleus. This
      translocation resulted in a characteristic apoptotic nuclear phenotype, which
      differs from the known nuclear phenotype of caspase-mediated chromatin
      condensation and apoptotic body formation. Interestingly both, AIF translocation
      and AIF-induced nuclear phenotype changes can be inhibited by NO scavengers,
      demonstrating the distinct role of nitrite-derived NO in the observed processes.
      This mode of UVA-induced apoptosis is AIF-dependent and NO-mediated and strongly
      depends on the presence of nitrite, abundantly present in skin tissue. Thus,
      photolysis of nitrite in the skin appears to represent an important backup
      mechanism, which ensures removal of UVA-damaged cells even in the absence of
      caspase activation.

PMID- 19844668
TI  - [Development and perspectives for orthopedic and trauma research in Germany].
AB  - The conditions for experimental orthopedic and trauma research in Germany have
      improved during recent years. At present, however, only a few research centers
      provide significant and continuous research. Recently advertised new
      professorships considerably enhance the chances of further improvement and it is
      hoped that this process will continue. The recruitment of orthopedic and trauma
      surgeons for professional research remains an unsolved problem due to financial
      and working conditions. To do both qualified research and clinical work on a high
      level over a long period of time is hardly possible within the existing
      structures. This problem can only be solved by establishing professional research
      laboratories with permanent scientific and technical staff and limited leave of
      absence for doctors from clinical work. Even in the future professional research
      departments and centers will have a notable advantage in the competition for
      research grants. Looking ahead there is hope that the conditions for orthopedic
      and trauma research will continue to improve and gain a relevance reflecting the
      importance of this field.

PMID- 19844669
TI  - [Microsurgical thumb replantation following traumatic amputation: preliminary
      results in Hanoi, Vietnam].
AB  - INTRODUCTION: Replantation using microsurgical techniques is a fairly new
      procedure in Vietnam. We reviewed and evaluated our 7-year results of thumb
      replantation in Vietnamese patients following traumatic thumb amputation.
      MATERIAL AND METHODS: Traumatic thumb amputations between September 1999 and July
      2006 were reexamined and evaluated. Postoperative functional results were
      evaluated based on four main criteria: 1) the patient's subjective attitude
      regarding the replanted thumb, 2) the degree of mobility of the replanted thumb
      compared with its counterpart, 3) the level of sensitivity of the replanted
      thumb, and 4) the objective ability to perform daily tasks. RESULTS: A total of
      26 patients were documented. The duration of follow-up averaged 22 months (range
      6-72 months). The success rate of replantation was 81%. A rating of either "good"
      or "very good" was obtained for 81% of the replanted thumbs. DISCUSSION: Vascular
      thrombosis was the cause of all failures. Proper debridement, standardized
      microvascular techniques, timely detection of thrombosis formation, and
      reoperation using vein grafts play a decisive role in the final success.

PMID- 19844667
TI  - Regulation of type 1 diabetes, tuberculosis, and asthma by parasites.
AB  - Helminth infection is a worldwide health problem. In addition to directly causing
      disease, helminthic infection also affects the incidence and progression of other
      diseases by exerting immune modulatory effects. In animal models, infection with
      helminthic parasites can prevent autoimmune diseases and allergic inflammatory
      diseases, but worsens protective immunity to certain infectious pathogens. In
      this review, we summarize current findings regarding the effects of helminth
      infection on type 1 diabetes, tuberculosis, and asthma and discuss possible
      mechanisms through which helminthic parasites modulate host immunity.
      Investigating these mechanisms could lead to treatment strategies that
      specifically modulate the immune response as well as address fundamental
      questions in immunobiology.

PMID- 19844670
TI  - Prevalence and correlates of hepatitis C infection among male injection drug
      users in detention, Tehran, Iran.
AB  - For the benefit of planning for the future care and treatment of people infected
      with hepatitis C virus (HCV) and to help guide prevention and control programs,
      data are needed on HCV seroprevalence and associated risk factors. We conducted a
      cross-sectional sero-behavioral survey of injection drug users (IDU) detained for
      mandatory rehabilitation during a police sweep of Tehran, Iran, in early 2006.
      During the study period, a consecutive sample comprising 454 of 499 (91.0%) men
      arrested and determined to be IDU by urine test and physical examination
      consented to a face-to-face interview and blood collection for HCV antibody
      testing. Overall, HCV prevalence was 80.0% (95% confidence interval (CI) 76.2
      83.6). Factors independently associated with HCV infection included history of
      incarceration (adjusted OR 4.35, 95% CI 1.88-10.08), age of first injection < or
      =25 years (OR 2.72, 95% CI 1.09-6.82), and history of tattooing (OR 2.33, 95% CI
      1.05-5.17). HCV prevalence in this population of IDU upon intake to jail was
      extremely high and possibly approaching saturation. Findings support that
      incarceration is contributing to the increased spread of HCV infection in Iran
      and calls for urgent increased availability of HCV treatment, long-term
      preparation for the care of complications of chronic infection, and rapid scale
      up of programs for the primary prevention of parenterally transmitted infections
      among drug users.

PMID- 19844671
TI  - [Current aspects and medication therapy strategies for out-patient uro
      oncological therapy].

PMID- 19844672
TI  - Pancreatic duct replication is increased with obesity and type 2 diabetes in
      humans.
AB  - AIMS/HYPOTHESIS: In a high-fat-fed rat model of type 2 diabetes we noted
      increased exocrine duct replication. This is a predisposing factor for
      pancreatitis and pancreatic cancer, both of which are more common in type 2
      diabetes. The aim of the study reported here was to establish if obesity and/or
      type 2 diabetes are associated with increased pancreatic ductal replication in
      humans. METHODS: We obtained pancreas at autopsy from 45 humans, divided into
      four groups: lean (BMI <25 kg/m(2)); obese (BMI >27 kg/m(2)); non-diabetic; and
      with type 2 diabetes. Pancreases were evaluated after immunostaining for the duct
      cell marker cytokeratin and Ki67 for replication. RESULTS: We show for the first
      time that both obesity and type 2 diabetes in humans are associated with
      increased pancreatic ductal replication. Specifically, we report that (1)
      replication of pancreatic duct cells is increased tenfold by obesity, and (2)
      lean subjects with type 2 diabetes demonstrate a fourfold increase in replication
      of pancreatic duct cells compared with their lean non-diabetic controls.
      CONCLUSIONS/INTERPRETATION: Pancreatic duct cell replication is increased in
      humans in response to both obesity and type 2 diabetes, potentially providing a
      mechanism for the increased risk of pancreatitis and pancreatic cancer in those
      with obesity and/or type 2 diabetes.

PMID- 19844692
TI  - [Minor amputations for diabetic foot syndrome].
AB  - Minor amputations are frequently performed for neuroischemic or neuropathic
      lesions of the diabetic foot. Depending on the definition used, minor amputations
      can range from toe to Syme amputations. Minor amputations are often combined with
      necrosectomy and debridement. For early and optimal rehabilitation, as much vital
      tissue as possible should be conserved, especially considering the skeletal
      structures of the foot (borderline amputation). Minor amputations are of utmost
      importance for the prevention of ascending infections and reduce the duration of
      clinical and outpatient treatment. Minor amputations should be performed only by
      experienced surgeons and only if arterial perfusion is sufficient. They should be
      as tissue-conserving as possible and structured interdisciplinary postoperative
      care is mandatory. Metabolic control should be optimized. Controversial opinions
      exist with respect to the use of tourniquets, conservation or resection of
      cartilage and sesamoid bones, open amputation or primary closure of the wound,
      interdigital spacer function of toes, aseptic proximal transection of tendons,
      postoperative wound care, negative-pressure wound treatment and antibiotic
      therapy. In view of these controversies the most important minor amputation
      techniques are described and discussed.

PMID- 19844693
TI  - Acute gastrointestinal bleeding due to oesophageal varices: an unusual case of a
      thoracic spleen.

PMID- 19844694
TI  - Blunting the response to endotoxin in healthy subjects: effects of various doses
      of intravenous fish oil.
AB  - OBJECTIVE: To test the dose response effect of infused fish oil (FO) rich in n-3
      PUFAs on the inflammatory response to endotoxin (LPS) and on membrane
      incorporation of fatty acids in healthy subjects. DESIGN: Prospective, sequential
      investigation comparing three different FO doses. SUBJECTS: Three groups of male
      subjects aged 26.8 +/- 3.2 years (BMI 22.5 +/- 2.1). INTERVENTION: One of three
      FO doses (Omegaven10%) as a slow infusion before LPS: 0.5 g/kg 1 day before LPS,
      0.2 g/kg 1 day before, or 0.2 g/kg 2 h before. MEASUREMENTS AND RESULTS:
      Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF
      alpha, stress hormones) were collected. After LPS temperature, ACTH and TNF-alpha
      concentrations increased in the three groups: the responses were significantly
      blunted (p < 0.0001) compared with the control group of the Pluess et al. trial.
      Cortisol was unchanged. Lowest plasma ACTH, TNF-alpha and temperature AUC values
      were observed after a single 0.2 g/kg dose of FO. EPA incorporation into platelet
      membranes was dose-dependent. CONCLUSIONS: Having previously shown that the
      response to LPS was reproducible, this study shows that three FO doses blunted it
      to various degrees. The 0.2 g/kg perfusion immediately before LPS was the most
      efficient in blunting the responses, suggesting LPS capture in addition to the
      systemic and membrane effects.

PMID- 19844695
TI  - Value of procalcitonin for diagnosis of early onset pneumonia in hypothermia
      treated cardiac arrest patients.
AB  - PURPOSE: Early onset pneumonia is frequently reported after cardiac arrest,
      despite the fact that therapeutic hypothermia and post-resuscitation disease
      manifestations make it difficult to diagnose. We aimed to assess the ability of
      serum procalcitonin (PCT) measurements to help diagnose pneumonia in this
      setting. METHODS: Retrospective study of consecutive patients admitted to a
      single academic medical intensive care unit (ICU) for successfully resuscitated
      cardiac arrest (July 2006-March 2008). All patient files were reviewed to assess
      the development of pneumonia during the first 5 days of ICU stay. Serum PCT was
      measured at admission, days (D) 1, 2 and 3. RESULTS: Among 132 patients included,
      pneumonia was diagnosed in 86, and antibiotics were initiated in 115 patients
      during the first 5 days. PCT was significantly higher in patients with pneumonia
      at D1 (4.58 vs. 1.03 ng/ml, p = 0.017), D2 (3.76 vs. 0.73, p = 0.002) and D3
      (3.76 vs. 0.73, p = 0.046). Areas under the ROC curves were 0.59 at admission,
      0.64 at D1, 0.68 at D2 and 0.63 at D3. Using a threshold of 0.5 ng/ml, negative
      predictive values were 39% at admission, 42% at D1 and 52% at D2, whereas
      positive predictive values were 72, 68 and 70%, respectively. Patients with post
      resuscitation shock (n = 66) had significantly higher PCT levels than vasopressor
      free patients from D1 to D3. CONCLUSIONS: The diagnostic value of PCT is poor
      after cardiac arrest and should not be performed to assess early onset pneumonia.
      The post-resuscitation disease itself could play a major role in this lack of
      specificity and predictive value.

PMID- 19844696
TI  - Human breath analysis: methods for sample collection and reduction of localized
      background effects.
AB  - Solid-phase microextraction (SPME) was applied, in conjunction with gas
      chromatography-mass spectrometry, to the analysis of volatile organic compounds
      (VOCs) in human breath samples without requiring exhaled breath condensate
      collection. A new procedure, exhaled breath vapor (EBV) collection, involving the
      active sampling and preconcentration of a breath sample with a SPME fiber fitted
      inside a modified commercial breath-collection device, the RTube, is described.
      Immediately after sample collection, compounds are desorbed from the SPME fiber
      at 250 degrees C in the GC-MS injector. Experiments were performed using EBV
      collected at -80 degrees C and at room temperature, and the results compared to
      the traditional method of collecting exhaled breath condensate at -80 degrees C
      followed by passive SPME sampling of the collected condensate. Methods are
      compared in terms of portability, ease-of-use, speed of analysis, and detection
      limits. The need for a clean air supply for the study subjects is demonstrated
      using several localized sources of VOC contaminants including nail polish,
      lemonade, and gasoline. Various simple methods to supply clean inhaled air to a
      subject are presented. Chemical exposures are used to demonstrate the importance
      of providing cleaned air (organic vapor respirator) or an external air source
      (tubing stretched to a separate room). These techniques allow for facile data
      interpretation by minimizing background contaminants. It is demonstrated herein
      that this active SPME breath-sampling device provides advantages in the forms of
      faster sample collection and data analysis, apparatus portability and avoidance
      of power or cooling requirements, and performance for sample collection in a
      contaminated environment.

PMID- 19844697
TI  - Effects of DBS on precision grip abnormalities in essential tremor.
AB  - Deep brain stimulation (DBS) of the ventrolateral thalamus is a highly effective
      procedure for the treatment of essential tremor (ET). The regularity of
      repetitive, self-paced finger tapping is known to be abnormal in patients with ET
      and improved following DBS. However, the more complex timing that underlies force
      development in the hands in ET and after DBS has not been evaluated. In this
      pilot study, we assessed precision grip performance in seven ET subjects before
      and after 5 months of DBS. Ten healthy controls were also studied. ET subjects
      showed a significant increase in preload duration (235 +/- 145 vs. 82 +/- 49 ms)
      and peak negative load (-0.524 +/- 0.35 vs. -0.174 +/- 0.14 N) during grip-lift
      compared with healthy subjects. No difference in load duration was observed
      between the groups. Following DBS, the magnitude of the peak negative load was
      significantly reduced (P = 0.03). In contrast, the duration of the load phase was
      worsened (non-significant) after DBS. We conclude that defects in the control of
      distal musculature necessary for establishing a stable grip exist in ET, whereas
      proximal muscles necessary for object lift-off remain relatively intact. Further,
      synergy paradigms governing grip-lift coordination may also be impaired. Although
      DBS is successful in alleviating tremor in ET, it produces only a partial
      restoration of normal precision grip.

PMID- 19844698
TI  - Neuroimaging findings in pediatric Wernicke encephalopathy: a review.
AB  - Wernicke encephalopathy (WE) is an acute neurological disease resulting from
      dietary thiamine (vitamin B1) deficiency. WE is characterized by changes in
      consciousness, ocular dysfunction, and ataxia. Neuroradiologic findings usually
      show symmetric signal intensity alterations in the mammillary bodies, medial
      thalami, tectal plate, and periaqueductal area. Selective involvement of the
      cranial nerve nuclei, cerebellum, red nuclei, dentate nuclei, fornix, splenium,
      cerebral cortex, and basal ganglia characterize nonalcoholic WE patients.
      Furthermore, symmetric basal ganglia alterations with involvement of the putamen
      have only been observed in children. The incidence of WE is underestimated in
      both adult and pediatric patients. Interestingly, the frequency of WE in children
      appears to be similar to that observed in adults. The prognosis of the disease
      largely depends on the time from diagnosis to thiamine supplementation. The aim
      of this pediatric literature review is to provide an update on neuroradiologic
      findings in children affected by WE in an effort to determine pertinent clinical
      and imaging findings that can improve the detection and early identification of
      the disease. A thorough knowledge of the MRI findings of WE will assist in
      arriving at an early diagnosis, thereby reducing the morbidity and mortality
      associated with this disease in children.

PMID- 19844699
TI  - Treatment of a wide-necked aneurysm of the anterior cerebral artery using two
      Enterprise stents in "Y"-configuration stenting technique and coil embolization:
      a technical note.
AB  - The endovascular treatment of wide-necked aneurysms remains challenging. The "Y"
      stenting technique has been used for stent-assisted coil embolization of wide
      necked bifurcation aneurysms. So far, this technique has been described for
      aneurysms of the basilar apex or the middle cerebral artery bifurcation and only
      for open stent systems using the Neuroform stent. We report a 52-year-old woman
      with recurrence of a wide-necked aneurysm of the anterior cerebral artery that
      was successfully retreated by stent-assisted coiling using the "Y"-stenting
      technique with the Enterprise stent system.

PMID- 19844700
TI  - Effect of interdomain dynamics on the structure determination of modular proteins
      by small-angle scattering.
AB  - Multidomain proteins in which consecutive globular regions are connected by
      linkers are prevalent in nature (Levitt in Proc Natl Acad Sci USA 106:11079
      11084, 2009). Some members of this family have largely resisted structural
      characterization as a result of challenges associated with their inherent
      flexibility. Small-angle scattering (SAS) is often the method of choice for their
      structural study. An extensive set of simulated data for both flexible and rigid
      multidomain systems was analyzed and modeled using standard protocols. This study
      clearly shows that SAXS profiles obtained from highly flexible proteins can be
      wrongly interpreted as arising from a rigid structure. In this context, it would
      be important to identify features from the SAXS data or from the derived
      structural models that indicate interdomain motions to differentiate between
      these two scenarios. Features of SAXS data that identify flexible proteins are:
      (1) general attenuation of fine structure in the scattering profiles, which
      becomes more dramatic in Kratky representations, and (2) a reduced number of
      interdomain correlation peaks in p(r) functions that also present large D (max)
      values and a smooth decrease to 0. When modeling this dynamically averaged SAXS
      data, the structures obtained present characteristic trends: (1) ab initio models
      display a decrease in resolution, and (2) rigid-body models present highly
      extended conformations with a lack of interdomain contacts. The ensemble
      optimization method represents an excellent strategy to identify interdomain
      motions unambiguously. This study provides information that should help
      researchers to select the best modeling strategy for the structural
      interpretation of SAS experiments of multidomain proteins.

PMID- 19844702
TI  - Fermentative production of branched chain amino acids: a focus on metabolic
      engineering.
AB  - The branched chain amino acids (BCAAs), L-valine, L-leucine, and L-isoleucine,
      have recently been attracting much attention as their potential to be applied in
      various fields, including animal feed additive, cosmetics, and pharmaceuticals,
      increased. Strategies for developing microbial strains efficiently producing
      BCAAs are now in transition toward systems metabolic engineering from random
      mutagenesis. The metabolism and regulatory circuits of BCAA biosynthesis need to
      be thoroughly understood for designing system-wide metabolic engineering
      strategies. Here we review the current knowledge on BCAAs including their
      biosynthetic pathways, regulations, and export and transport systems. Recent
      advances in the development of BCAA production strains are also reviewed with a
      particular focus on L-valine production strain. At the end, the general
      strategies for developing BCAA overproducers by systems metabolic engineering are
      suggested.

PMID- 19844701
TI  - Membrane microheterogeneity: Forster resonance energy transfer characterization
      of lateral membrane domains.
AB  - Lateral membrane heterogeneity, in the form of lipid rafts and microdomains, is
      currently implicated in cell processes including signal transduction,
      endocytosis, and cholesterol trafficking. Various biophysical techniques have
      been used to detect and characterize lateral membrane domains. Among these,
      Forster resonance energy transfer (FRET) has the crucial advantage of being
      sensitive to domain sizes smaller than 50-100 nm, below the resolution of optical
      microscopy but, apparently, similar to those of rafts in cell membranes. In the
      last decade, several formalisms for the analysis of FRET in heterogeneous
      membrane systems have been derived and applied to the study of microdomains. They
      are critically described and illustrated here.

PMID- 19844703
TI  - N- and O-linked oligosaccharides completely lack galactose residues in the
      gms1och1 mutant of Schizosaccharomyces pombe.
AB  - Unlike their counterparts in budding yeast Saccharomyces cerevisiae, the
      glycoproteins of Schizosaccharomyces pombe contain, in addition to alpha-D
      mannose (Man), a large number of alpha-D-galactose (Gal) residues. In both
      yeasts, large outer chains are attached to the oligosaccharide cores of
      glycoproteins during export via Golgi. Formation of the yeast-specific large
      outer chain is initiated by alpha-1,6-mannosylatransferase encoded by the och1+
      gene, the disruption of which blocked outer chain elongation. We previously
      reported that N-linked oligosaccharide structures of S. pombe och1Delta mutant
      consisted of Gal(2-6)Man(9)GlcNAc(2) with alpha-linked Gal residues attached to
      the core oligosaccharide moiety. The disruption of gms1+, a gene encoding the UDP
      galactose transporter required for the synthesis of galactomannan, abolished cell
      surface galactosylation in S. pombe. In this study, we constructed a
      gms1Deltaoch1Delta double mutant and determined the N- and O-linked
      oligosaccharide structures present on the cell surface. Oligosaccharides were
      liberated from glycoproteins by hydrazinolysis and labeled with the fluorophore,
      2-aminopyridine. The pyridylaminated N-linked oligosaccharides were analyzed by
      high-performance liquid chromatography in combination with alpha1,2-mannosidase
      digestion and partial acetolysis. These analyses revealed that the N-linked
      oligosaccharides of gms1Deltaoch1Delta cells consisted of alpha1,2-linked Man
      extended core oligosaccharides (Man(8-12)GlcNAc2) from which the fission yeast
      specific alpha-linked Gal residues were completely absent.

PMID- 19844705
TI  - Analysis of extracellular alginate lyase and its gene from a marine bacterial
      strain, Pseudoalteromonas atlantica AR06.
AB  - Pseudoalteromonas atlantica AR06 is a marine bacterial strain that can utilize
      alginate as a sole source of carbon and energy. The extracellular protein
      fraction prepared from the AR06 cultivation media exhibited alginate lyase
      activity to depolymerize the alginate molecules having homopolymeric and
      heteropolymeric forms of mannuronate and guluronate so as to mainly convert into
      the dimer to tetramer. A DNA fragment encoding a portion of alginate lyase was
      amplified from AR06 genomic DNA by PCR using a set of degenerated primers, and
      then the whole alginate lyase gene, named alyA, and its flanking regions were
      obtained from a cosmid library of AR06 genomic DNA. The alyA mutant of AR06
      showed (1) the loss of alginate depolymerization activity on alginate agar plate
      and (2) significant growth defects in alginate minimal medium; these defects were
      complemented by the introduction of the alyA gene. Furthermore, zymography and
      biochemical analyses revealed that three extracellular protein bands of AR06 had
      alginate lyase activities and that all three protein bands were derived from the
      nascent alyA gene product. These results clearly indicated that the alyA gene
      greatly contributes to the assimilation of alginate in AR06. The transcription of
      the alyA gene was induced by the presence of alginate in minimal medium, but its
      obvious induction was not observed in rich medium even in the presence of
      alginate.

PMID- 19844704
TI  - Characterization of corrosive bacterial consortia isolated from petroleum-product
      transporting pipelines.
AB  - Microbiologically influenced corrosion is a problem commonly encountered in
      facilities in the oil and gas industries. The present study describes bacterial
      enumeration and identification in diesel and naphtha pipelines located in the
      northwest and southwest region in India, using traditional cultivation technique
      and 16S rDNA gene sequencing. Phylogenetic analysis of 16S rRNA sequences of the
      isolates was carried out, and the samples obtained from the diesel and naphtha
      transporting pipelines showed the occurrence of 11 bacterial species namely
      Serratia marcescens ACE2, Bacillus subtilis AR12, Bacillus cereus ACE4,
      Pseudomonas aeruginosa AI1, Klebsiella oxytoca ACP, Pseudomonas stutzeri AP2,
      Bacillus litoralis AN1, Bacillus sp., Bacillus pumilus AR2, Bacillus
      carboniphilus AR3, and Bacillus megaterium AR4. Sulfate-reducing bacteria were
      not detected in samples from both pipelines. The dominant bacterial species
      identified in the petroleum pipeline samples were B. cereus and S. marcescens in
      the diesel and naphtha pipelines, respectively. Therefore, several types of
      bacteria may be involved in biocorrosion arising from natural biofilms that
      develop in industrial facilities. In addition, localized (pitting) corrosion of
      the pipeline steel in the presence of the consortia was observed by scanning
      electron microscopy analysis. The potential role of each species in biofilm
      formation and steel corrosion is discussed.

PMID- 19844706
TI  - A new methodology combining PCR, cloning, and sequencing of clones discriminated
      by RFLP for the study of microbial populations: application to an UASB reactor
      sample.
AB  - This work describes a methodology combining DNA extraction, polymerase chain
      reaction amplification with primers targeting 16S ribosomal RNA genes, cloning,
      and sequencing of clones previously analyzed by restriction fragment length
      polymorphism (RFLP), which can be applied to study the microbial diversity in a
      given habitat. The methodology allows the minimization of the sequencing effort,
      which is particularly relevant when analyzing large numbers of clones. The
      methodology does not require particularly skilled personnel and can easily be
      adaptable to the molecular characterization of virtually any particular microbial
      population, provided that both adequate primers and suitable restriction enzymes
      for RFLP analysis of the clone library have been chosen. An example of
      application is presented, in which a sample taken from a continuously operating
      upflow anaerobic sludge blanket reactor was analyzed. RFLP analysis of the
      initial 162 clones with HaeIII allowed the identification of only 28 distinct
      profiles. As expected, identical RFLP profiles corresponded to identical
      nucleotide sequences.

PMID- 19844707
TI  - Progress and challenges in neuroendocrine and neural crest tumours: molecular
      imaging and therapy.

PMID- 19844708
TI  - Minimally invasive plate osteosynthesis for humeral shaft fractures: are results
      reproducible?
AB  - Minimally invasive plate osteosynthesis (MIPO) has been advocated as a safe
      approach to humeral shaft fracture management. We evaluated the reproducibility
      of this technique in a regional hospital. Thirty-five patients underwent MIPO of
      humerus shaft fractures. Fifteen patients had an open fracture, six a
      preoperative radial nerve palsy, and nine a concomitant thoracic, musculoskeletal
      or vascular injury. At an average 12-month follow-up, 91% of fractures healed
      after a mean of 12 weeks (range, 8-16). Two infections occurred. Final alignment
      averaged 4 degrees  of varus (range, 5 degrees  of valgus to 20 degrees  of
      varus). Active elbow ROM averaged 114 degrees  (range, 60-135 degrees ) and was
      less than 100 degrees  in nine elbows. Five of six preoperative radial nerve
      injuries recovered spontaneously. Healing and infection rates in this study are
      consistent with those reported in the literature. Lower elbow ROM and higher
      fracture angulation at healing were nevertheless found. MIPO is technically
      demanding and requires adequate intraoperative imaging and surgical experience in
      order to obtain adequate fracture alignment. Brachialis muscle scarring and
      inadequate postoperative rehabilitation may be involved in limited elbow range of
      motion.

PMID- 19844710
TI  - Plasmablastic crisis of Philadelphia chromosome-positive chronic myeloid
      leukemia.

PMID- 19844709
TI  - Efficacy of minimally invasive techniques for enhancement of fracture healing:
      evidence today.
AB  - The successful treatment of nonunions represents a major challenge for
      orthopaedic surgeons. Lately, ongoing advances made in the field of molecular
      medicine and molecular biology have increased our understanding of the pathways
      and involvement of mediators surrounding the bone healing process. As a result,
      the surgeon's armamentarium has been increased in terms of options for
      intervention. This article aims to provide an overview of minimally invasive
      techniques applicable in the treatment of nonunions of fractures.

PMID- 19844711
TI  - 18F-FDG PET/CT in primary non-Hodgkin's lymphoma of the sinonasal tract.

PMID- 19844712
TI  - Serum albumin level is a significant prognostic factor reflecting disease
      severity in symptomatic multiple myeloma.
AB  - Serum albumin level, in association with serum interleukin-6 level, is a
      significant prognostic factor in multiple myeloma patients. The aim of this study
      was to determine any clinical factors associated with decreased serum albumin
      level. We retrospectively reviewed the records of 373 patients diagnosed with
      multiple myeloma at the Asan Medical Center, Seoul, Korea, between January 1996
      and March 2008. Patients were divided into two groups according to serum albumin
      level (above or below 3.5 g/dL, the prognostic cutoff value), and clinical
      parameters were compared between groups. We aimed to identify any clinical
      parameters associated with low serum albumin levels. The group with serum albumin
      <3.5 g/dL showed older patient age, lower hemoglobin level, and poorer
      performance status. By contrast, levels of serum beta(2)-microglobulin, serum M
      protein, and bone marrow plasma cells were significantly higher in the group with
      low serum albumin levels. No significant between-group differences were found
      when serum calcium and creatinine levels were compared. Numbers of cytogenetic
      abnormalities and lytic bone lesions also showed no significant between-group
      differences. In both univariate and multivariate analyses, serum albumin level
      less than 3.5 g/dL was identified as a significant pretreatment prognostic
      factor. Lower serum albumin levels in multiple myeloma patients are associated
      with clinical factors reflecting disease severity.

PMID- 19844713
TI  - ABO discrepancy in a young Korean serviceman with common variable
      immunodeficiency.

PMID- 19844714
TI  - Cisplatin administration following carboplatin desensitization failure in primary
      peritoneal cancer: a brief report.
AB  - PURPOSE: Platinum-based therapy is the cornerstone of ovarian cancer treatment.
      Development of platinum hypersensitivity can limit therapeutic options. In this
      brief report, we present case of successful cisplatin administration following
      two unsuccessful carboplatin desensitization attempts, and without the need for
      pre-treatment steroids. METHODS: Retrospective chart review was performed.
      RESULTS: One case of recurrent primary peritoneal carcinoma previously treated
      with a carboplatin-based regimen, developed a platinum hypersensitivity. Two
      attempts at carboplatin desensitization were unsuccessful. Cisplatin was
      substituted and the patient achieved a complete response to therapy without
      further hypersensitivity. CONCLUSIONS: Platinum-based therapies are vital to the
      treatment of primary peritoneal and ovarian carcinoma. Protocols that
      successfully incorporate platinum agents, despite a platinum hypersensitivity,
      are clinically relevant.

PMID- 19844715
TI  - [Pleomorphic adenoma: pitfalls and clinicopathological forms of progression].
AB  - In the majority of cases the diagnosis of pleomorphic adenoma (PA) is
      straightforward. In "monomorphic" types of PA problems may result: Epithelial
      rich PA need to be distinguished from basal cell adenoma or canalicular adenoma.
      PA dominated by mesenchymal, spindle-shaped differentiation need to be
      distinguished from myoepithelioma or soft tissue tumours like schwannoma. Focal
      biphasic-tubular differentiation with CK7/18-positive ductal cells is good
      evidence for a tumour within the wide spectrum of PA. Focal peripheral
      pseudoinfiltration can represent physiological growth pattern of PA; this may
      render a difficult distinction from low-malignant carcinomas like adenoid-cystic
      or epithelial-myoepithelial carcinoma, harbouring also tubular structures. The
      different progression steps of carcinoma ex pleomorphic adenoma (CEPA), starting
      with intraductal carcinoma, are highly relevant with respect to prognosis and
      therapy. Early stages including CEPA with minor extracapsular invasion show
      favourable prognosis, while cases with extensive extracapsular invasion carry a
      dismal prognosis.

PMID- 19844716
TI  - DNase1 activity in systemic lupus erythematosus patients with and without
      nephropathy.
AB  - The objective of the study is to determine whether the activity of DNase1 is
      associated to the presence of nephropathy in patients with SLE. Forty-five
      patients affected with SLE and renal involvement were analyzed. The type of renal
      involvement was type III or IV glomerulonephritis. At least two serum samples
      were withdrawn from each patient, one obtained in a renal flare and the other
      obtained in a period of clinical stability. C3 and C4 complement levels and anti
      DNA antibodies were determined. DNase1 activity was measured using a radial
      enzyme-diffusion method. Results suggest that when comparison of DNase1 activity
      was established between samples obtained during a phase of active renal
      involvement and those obtained in the clinically stable phase, we did not find
      statistically significant differences. When the comparison was performed with
      matched samples of the same patient, DNase1 activity was lower when patients had
      active renal involvement than when samples were taken in clinically stable phase
      (21.21 MUg/ml +/- 16.47 vs. 25.62 MUg/ml +/- 18.81, p < 0.05). No difference in
      DNase1 activity was observed between samples positive or negative for anti-DNA
      antibodies. No difference in DNase1 activity was found in patients with normal or
      decreased levels of C3 (25.09 MUg/ml +/- 17.78 vs. 20.01 MUg/ml +/- 16.15, p =
      0.073) or C4 (23.52 MUm/ml +/- 16.60 vs. 19.62 MUg/ml +/- 17.54, p = 0.060). We
      conclude that low DNase1 activity is associated to the active phase of type III
      or IV nephropathy. Therefore, it is possible that this enzyme plays an important
      role in the development of SLE nephropathy.

PMID- 19844717
TI  - Pseudo-pseudo Meigs syndrome developed under the leflunomide therapy.
AB  - Pseudo-pseudo Meigs syndrome or Tjalma syndrome is characterized by increased CA
      125 level, pleural effusion and ascites in systemic lupus erythematosus (SLE)
      patients without over tumor. The disorder is relatively rare and it has been
      reported usually in SLE patients with impaired renal functions. Herein, we
      present a case of a 47-year-old female patient who developed Tjalma syndrome
      after administration of leflunomide for rheumatoid arthritis. Surprisingly renal
      functions of our patient were found in normal limits. This is the first case of
      Tjalma syndrome that is developed in normal renal functions and the probable role
      of leflunomide therapy is discussed.

PMID- 19844718
TI  - Follow-up results of 702 patients receiving tumor necrosis factor-alpha
      antagonists and evaluation of risk of tuberculosis.
AB  - The objective of this study is to estimate the incidence of active tuberculosis
      in patients with inflammatory diseases receiving tumor necrosis factor-alpha (TNF
      alpha) antagonists and to figure out the characteristics of patients who develop
      tuberculosis. 702 patients with different inflammatory diseases receiving TNF
      alpha antagonists were followed up from August 2005 to July 2008 at our
      department of chest disease. All patients had tuberculin skin test (TST) and
      postero-anterior chest radiograph (CXR) prior to anti TNF-alpha antagonist
      treatment. All patients with a TST result > or =5 mm or fibrotic lesions on CXR
      were administered chemoprophylaxis with isoniazid (INH) for 9 months. 6 (0.85%)
      patients developed active tuberculosis (4 pulmonary and 2 extrapulmonary) during
      the follow-up period. TST was found to be positive in 434 (61.8%) of the
      patients. Patients, who were already on immunosuppressive therapy and who were
      not, were compared for the difference in their TST results and no statistically
      significant difference was found. Chemoprophylaxis was administered overall to
      583 (83.0%) patients among which 31 (5.3%) developed hepatotoxicity. Of the
      patients who developed active tuberculosis, all were decided to receive INH
      chemoprophylaxis, however, only three of them adhered proper treatment.
      Diagnostic accuracy of TST for detecting latent tuberculosis is high among
      patients with inflammatory diseases even in the setting of immunosuppression. The
      risk of development of active TB is increased in this group of patients despite
      chemoprophylaxis, but this risk remains within the acceptable limits even in a
      moderate-tuberculosis incidence country, if proper chemoprophylaxis regimen is
      adhered.

PMID- 19844719
TI  - Intravenous immunoglobulin treatment for pregnancy-associated dermatomyositis.
AB  - Pregnancy-associated dermatomyositis (DM) is a rare disorder, until recently
      treated only with corticosteroids due to the toxicity of other immunosuppressive
      agents for the fetus. We present a pregnant woman with DM treated successfully
      with intravenous immunoglobulin (IVIG) and medium dose corticosteroids. A 42-year
      old woman presented with a rash, muscle weakness and increased muscle enzymes on
      the 15th week of her first pregnancy. After the diagnosis of DM she was treated
      with the combination of medium dose corticosteroids and IVIG. The patients'
      symptoms resolved rapidly. No complications were noted for either her or the
      fetus. Both she and her son remain disease-free after 6 years follow-up. In
      conclusion, IVIG treatment is a safe and effective alternative for pregnancy
      associated DM.

PMID- 19844720
TI  - Lung involvement in patients with primary Sjogren's syndrome: what are the
      predictors?
AB  - The aim of this study was to investigate the prevalence, predictors and
      radiological findings of primary Sjogren's syndrome (pSS)-associated lung
      involvement. This retrospective cohort study included 123 patients with
      demographic, clinical, laboratory and radiological data who were diagnosed with
      pSS. Lung involvement was defined based on the presence of pulmonary
      signs/symptoms and/or impaired pulmonary function tests along with alterations in
      high-resolution computerized tomography (HRCT). Thirty patients (24.4%) had
      pulmonary signs/symptoms at the initial presentation and/or during the follow-up
      period. Based on the criteria, 14 patients (11.4%) were defined as having pSS
      with lung involvement. The smoking rate, male/female ratio and the mean ages were
      found to be higher in patients with lung involvement (P < 0.05). Positive IgM
      rheumatoid factor (RF), anti-La and anti-Ro results, the presence of
      hypergammaglobulinemia and lymphopenia had high specificity despite the low
      sensitivity rates to detect pSS-associated lung disease. A significant difference
      was found in forced vital capacity (FVC) and forced expiratory volume in 1 s
      (FEV(1)) results between the patients with and without lung involvement. Impaired
      FEV(1) had high specificity and positive predictive value compared to impaired
      FVC, particularly in non-smoker patients. The most frequent HRCT finding was
      ground-glass attenuation (64.3%). Other common findings were bronchiectasis,
      reticular pattern and honeycombing. The lesions involved predominantly the lower
      lobes. In conclusion, the presence of hypergammaglobulinemia and lymphopenia,
      positivity for RF, anti-La and anti-Ro, and impaired (FVC) and/or FEV(1) values
      could be the predictive parameters with a high specificity despite the low
      sensitivity rates. Smoking history, male gender and age are also risk factors.
      These parameters may be helpful to distinguish pSS-associated lung involvement
      from lung disorders unrelated to pSS.

PMID- 19844721
TI  - [Effectiveness and relevance of laser trabeculoplasty: treatment of open-angle
      glaucoma].
AB  - Laser trabeculoplasty is a common glaucoma therapy that is safe and effective for
      reducing intraocular pressure. It was developed as a treatment for open-angle
      glaucoma in the 1970s, and larger studies proved its effectiveness in the years
      that followed. In recent years, through the implementation of newer processes
      such as selective laser trabeculoplasty, laser trabeculoplasty has experienced
      further developments. Because it causes less damage to the trabecular meshwork,
      it should have fewer adverse effects, making it a repeatable treatment. Studies
      on the indications, contraindications, and effectiveness of this method in
      lowering intraocular pressure are reviewed.

PMID- 19844722
TI  - [Laser trabeculoplasty: therapeutic options and adverse effects].
AB  - Laser trabeculoplasty is a simple method for treating glaucoma and ocular
      hypertension and has few adverse effects. There are different laser systems for
      reducing the intraocular pressure of patients with glaucoma and ocular
      hypertension. Complications include transient intraocular pressure elevation,
      iritis, and anterior synechiae.

PMID- 19844723
TI  - [Available laser systems and mechanism of action in laser trabeculoplasty].
AB  - Intraocular pressure-lowering laser procedures such as argon laser
      trabeculoplasty and selective laser trabeculoplasty are nowadays an essential
      part of glaucoma therapy. This article presents the currently most popular laser
      systems. These various laser procedures are based on the physical structure of
      the different lasers and on variable generation of laser light. They vary in
      their effect on the trabecular meshwork on a histopathological level, as well as
      in the active principles of intraocular pressure reduction. The mechanical,
      biological, and repopulation theories are currently used to explain the
      intraocular pressure-lowering effect of the different laser systems; these are
      discussed in detail.

PMID- 19844724
TI  - Downregulation of insulin-like growth factor binding protein 3 and 5 in nitrofen
      induced pulmonary hypoplasia.
AB  - PURPOSE: The high mortality in congenital diaphragmatic hernia (CDH) is mainly
      attributed to pulmonary hypoplasia. Recent studies suggest that retinoid
      signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung.
      The insulin-like growth factor (IGF) system plays a crucial role in fetal lung
      development by interaction of IGFBP-3 and IGFBP-5 with RSP. We hypothesized that
      pulmonary IGFBP-3 and IGFBP-5 gene expression levels are downregulated in the
      nitrofen-induced pulmonary hypoplasia. METHODS: Pregnant rats were exposed to
      either olive oil or 100 mg nitrofen on day 9.5 (D9.5) of gestation. Fetal lungs
      were harvested on D18 and D21 and divided into control and nitrofen groups. IGFBP
      3 and IGFBP-5 pulmonary gene and protein expression were determined using real
      time RT-PCR and immunohistochemistry. RESULTS: Relative levels of IGFBP-3 mRNA
      were significantly decreased in the nitrofen group (8.00 +/- 14.44) in D21
      compared to controls (14.81 +/- 16.11; p < 0.05). Expression levels of IGFBP-5
      mRNA were also significantly decreased in nitrofen group (10.66 +/- 4.83) on D18
      compared to controls (17.92 +/- 4.77). Immunohistochemistry showed decreased
      IGFBP-3 expression on D21 and decreased IGFBP-5 immunoreactivity on D18 in
      hypoplastic lungs compared to controls. CONCLUSION: Downregulation of IGFBP-3 and
      IGFBP-5 gene expression may cause pulmonary hypoplasia in the nitrofen-induced
      CDH model by interfering with retinoid signaling pathway.

PMID- 19844725
TI  - Management of acute appendicitis: an imaging strategy in children.
AB  - The pre-operative diagnosis of acute appendicitis (AA) has markedly changed
      during the last couple of decades due to the advent of modern imaging technology.
      Nowadays, the use of imaging has dramatically changed the way we approach
      children admitted to emergency room for abdominal pain with suspected AA. This
      change is mainly manifested in our diagnostic strategy.

PMID- 19844726
TI  - Neonatal pneumoperitoneum: a critical appraisal of its causes and subsequent
      management from a developing country.
AB  - BACKGROUND: The diagnosis and management of neonatal pneumoperitoneum revolves
      around necrotizing enterocolitis (NEC) in most of the published literature.
      Although NEC remains the major cause of pneumoperitoneum in a neonate, there are
      several other causes leading to free air in the peritoneal cavity. A number of
      case reports have appeared describing pneumoperitoneum in a newborn due to
      rupture of one particular organ, but there have been only few collective reviews
      on the subject. The present study shares the experience with neonates admitted
      with a diagnosis of pneumoperitoneum in a pediatric surgical center of a
      developing country. The various causes of pneumoperitoneum in a newborn, their
      management and subsequent outcome are described. MATERIALS AND METHODS: The study
      was conducted in the Department of Pediatric Surgery, CSMMU (upgraded King
      Georges Medical College), Lucknow, India. All the neonates admitted with a
      diagnosis of pneumoperitoneum during the period of last 3 years (2005-2008) were
      retrospectively analyzed. Other neonatal admissions were also retrieved for the
      same period. Free air was confirmed by erect abdominal X-ray or lateral decubitus
      films in certain cases. The data sheets were analyzed regarding age of
      presentation, cause of bowel perforation, management offered and subsequent
      outcome achieved. All patients of NEC without evidence of perforation were not
      included in the study (n = 21). RESULTS: Out of total 537 neonatal admissions, 89
      (16.5%) neonates were admitted with a diagnosis of pneumoperitoneum. There were
      79 (88.7%) males and only 10 (11.6%) female neonates admitted during the study
      period. All of them had evidence of pneumoperitoneum at the time of admission.
      The age at presentation ranged from 4 to 32 days. NEC remained the single major
      cause of pneumoperitoneum in the newborn; however, in 44 (49.4%) patients the
      cause was not related to NEC. Perforated pouch colon, isolated colonic
      perforations, caecal perforations, gastric and duodenal perforations were the
      main causes of pneumoperitoneum not related to NEC. There were seven patients in
      whom no cause of pneumoperitoneum could be ascertained. The treatment was
      individualized according to the presentation. Most of the NEC-related
      perforations were managed by peritoneal drains. Laparotomy was done in rest of
      the patients. Three patients were managed conservatively. Overall, 19 (21.6%)
      patients expired. Most of those expired were of low birth weight with NEC and
      congenital pouch colon with perforation. CONCLUSION: Neonatal pneumoperitoneum
      remains a surgical emergency and outcome can be lethal if the problem is not
      addressed early. NEC remains the major cause; however, there are several other
      important causes of isolated gastrointestinal perforations leading to neonatal
      pneumoperitoneum. The management should be individualized in these patients and
      the outcome largely depends on the early recognition of the condition.

PMID- 19844727
TI  - Fulminant amebic colitis with lower GI bleed with liver abscess.

PMID- 19844728
TI  - Rectal endosonography: just how good are we at its interpretation?
AB  - BACKGROUND: Endorectal ultrasound (ERUS) has become an integral part of the
      assessment of rectal tumors. It provides information about the depth of invasion
      and lymph node status which in turn is used in devising a management plan. It is
      important therefore that accurate interpretation of these studies is achieved.
      The aim of this study was to assess how accurately we interpret ERUS. STUDY
      DESIGN: A collection of 26 ERUS images were compiled and confirmed by two
      experienced colorectal sonographers. The survey was sent to 100 ASCRS members
      practicing at institutions with residency programs in colorectal surgery in USA
      and Canada. Two separate mailings were sent. Participants were asked to allocate
      a T and N stage to each of the images. Their responses were compared with
      pathology results. RESULTS: Twenty five surveys were returned, 23 were completed.
      Thirteen respondents reported performing ERUS themselves, on average performing
      three examinations per month (range, 1-8). The mean duration of practice was 11.2
      years (range, 0-26). The mean number of rectal cancer cases managed over a 12
      month period was 25 (range, 10-75). T stage was accurately reported in 38-69%.
      CONCLUSIONS: If we continue to rely on ERUS as an important step in staging
      rectal cancer further education may be needed to improve overall interpretation.

PMID- 19844729
TI  - Effect of hemorrhoidectomy on anorectal physiology.
AB  - PURPOSE: The aim of this study was to determine whether overactivity of the anal
      sphincter in patients with hemorhhoids is primary or secondary and thus assess
      indication of lateral internal sphincterotomy to surgical treatment of
      hemorrhoids. Tonic contraction of the sphincter muscle in patients with advanced
      stages of hemorrhoids is considered by many authors as a primary cause, and
      therefore, they complete hemorrhoid surgery with lateral internal sphincteroomy.
      If hypertension of anal sphincter is secondary during hemorrhoid disease, lateral
      internal sphincterotomy is not indicated. Although examinations made immediately
      after sphincterotomy proved no changes of anal continence, certain sequelae of
      lateral internal sphincterotomy cannot be excluded and may later negatively
      affect patient's anal continence. PATIENTS AND METHODS: The prospective study
      comprised 385 patients treated in 2002-2006 by Hemoron or surgery according to
      Milligan-Morgan or Longo. Patients with history of another disease of the anal
      canal, radiotherapy of pelvis, Crohn's disease or ulcerous colitis were excluded.
      Manometry was performed before and after surgery at intervals of 1, 3, 6 and 12
      months after operation using a perfusion flow method, six-channels catheter with
      radial arrangement of channel tips. RESULTS: In all three groups (Hemoron, sec.
      Milligan-Morgan, sec. Longo), there were 60-65% of patients with third degree
      hemorrhoids. Normal resting anal pressure before surgery was recorded in only 25%
      of men and 30% of women. Patients with advanced hemorrhoid degrees were found to
      have significant hypertension of the anal sphincter. The most significantly
      improved state of sphincter overactivity was observed after surgery according to
      Longo and application of Hemoron. After surgery, according to Milligan-Morgan,
      recovery of anal sphincter tension was the longest; even 6 months after
      operation, a mean increased resting anal pressure persisted (91-110 mmHg) in 25%
      of men and 19% of women. After 12 months, recovery of anal tension occurred in
      this group also--mean increased anal pressure was recorded in only three patients
      (1.67%). CONCLUSION: Overactivity of the anal sphincter in patients with
      hemorrhoids is secondary and according to our results. Hypertension of the
      sphincter muscle in patients with hemorrhoids is significantly increased in
      patients with advanced degrees of hemorrhoids. Therefore, it is not recommended
      to postpone surgery and indicate patients with advanced degrees of hemorrhoids to
      hemorrhoidectomy.

PMID- 19844730
TI  - Frontotemporal lobar degeneration: toward the end of conFUSion.

PMID- 19844731
TI  - Novel neuropathologic findings in the Haddad syndrome.
AB  - Haddad syndrome (congenital central hypoventilation syndrome and Hirschsprung's
      disease) is a rare disorder for which in-depth neuropathologic analysis is
      lacking. We report the brain findings in a full-term male infant with Haddad
      syndrome who died at 27 days of life. Bilateral hypoplasia of the superior
      temporal lobe and gyral anomalies in the frontal cortex were present.
      Immunohistochemistry with an antibody to tyrosine hydroxylase (noradrenaline
      synthesis) demonstrated hypoplasia of the locus coeruleus (implicated in
      chemoreception) and A5 region. Other findings included delayed maturation of the
      arcuate nucleus (putative human homologue of ventral medullary neurons in animals
      critical for chemoreception) and aberrant fascicles in the nucleus of the
      solitary tract. Efforts to determine the putative gene mutation were
      unsuccessful. This study implicates novel brain findings in Haddad syndrome
      mimicking those in murine Phox2b null mutants. This case suggests that
      abnormalities occur in CCHS in a network of sites critical to chemoreception.

PMID- 19844732
TI  - Absence of FUS-immunoreactive pathology in frontotemporal dementia linked to
      chromosome 3 (FTD-3) caused by mutation in the CHMP2B gene.

PMID- 19844733
TI  - Autoantibody against one of the antioxidant repair enzymes, methionine sulfoxide
      reductase A, in systemic sclerosis: association with pulmonary fibrosis and
      vascular damage.
AB  - Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis
      and vascular changes in the skin and internal organs with autoimmune background.
      It has been suggested that oxidative stress plays an important role in the
      development of SSc. To determine the prevalence and clinical correlation of
      autoantibody to methionine sulfoxide reductase A (MSRA), one of the antioxidant
      repair enzymes, in SSc, serum anti-MSRA autoantibody levels were examined in
      patients with SSc by enzyme-linked immunosorbent assay using recombinant MSRA.
      The presence of anti-MSRA antibody was evaluated by immunoblotting. To determine
      the functional relevance of anti-MSRA antibody in vivo, we assessed whether anti
      MSRA antibody was able to inhibit MSRA enzymatic activity. Serum anti-MSRA
      antibody levels in SSc patients were significantly higher compared to controls
      and this autoantibody was detected in 33% of SSc patients. Serum anti-MSRA levels
      were significantly elevated in SSc patients with pulmonary fibrosis, cardiac
      involvement, or decreased total antioxidant power compared with those without
      them. Anti-MSRA antibodies also correlated positively with renal vascular damage
      determined as pulsatility index by color-flow Doppler ultrasonography of the
      renal interlobar arteries and negatively with pulmonary function tests.
      Furthermore, anti-MSRA antibody levels correlated positively with serum levels of
      8-isoprostane and heat shock protein 70 that are markers of oxidative and
      cellular stresses. Remarkably, MSRA activity was inhibited by IgG isolated from
      SSc sera containing IgG anti-MSRA antibody. These results suggest that elevated
      anti-MSRA autoantibody is associated with the disease severity of SSc and may
      enhance the oxidative stress by inhibiting MSRA enzymatic activity.

PMID- 19844734
TI  - Umbilical cord blood amino-terminal pro-brain natriuretic peptide levels
      according to the mode of delivery.
AB  - PURPOSE: To evaluate cord blood amino-terminal pro-brain natriuretic peptide (NT
      proBNP) levels according to the mode of delivery. METHOD: Between 1 March and 31
      May 2007, 106 blood samples were drawn from the umbilical vein at the time of
      delivery. Eighty-four NT-proBNP levels [63 term (34 cesarean sections and 29
      vaginal deliveries) and 21 preterm births] were analyzed with respect to
      gestational age, birth weight, Apgar score, newborn gender, and cord blood pH.
      RESULTS: There was no statistical significance on comparison of the mean NT
      proBNP values between the cesarean and vaginal delivery groups (801.9+/-537.7 vs.
      724.3+/-542.4 pg/ml, respectively; P=0.572). The correlation of NT-proBNP with
      gestational age, birth weight, and cord blood pH was -0.616, -0.585, and -0.202,
      respectively. The mean values for NT-proBNP levels were compared according to the
      newborn gender (male vs. female; P=0.926), and Apgar score at 1 min [>6 (N=71)
      vs. <or=6 (N=13); P=0.001]. CONCLUSION: Vaginal delivery did not result in
      increased cord blood NT-proBNP levels reflecting cardiovascular stress to the
      fetal heart. NT-proBNP was inversely correlated with gestational age. Low Apgar
      score and umbilical cord blood pH appeared to induce the fetus to produce
      increased amounts of NT-proBNP.

PMID- 19844735
TI  - Exercise-induced laryngeal obstructions objectively assessed using EILOMEA.
AB  - We describe a diagnostic software measuring tool (EILOMEA) to objectively
      describe images obtained by the continuous laryngoscopic exercise (CLE) test, and
      assess the reproducibility and clinical applications of this tool for the
      diagnosis of exercise-induced laryngomalacia (EIL) and exercise-induced vocal
      cord dysfunction (EI-VCD). A total of 97 subjects, 14-24 years of age, were
      tested with a CLE test. For each laryngoscopic recording, the severity of EIL
      and/or EI-VCD was assessed by an expert and compared with data obtained using
      EILOMEA. For both EIL and EI-VCD, a separate objective factor was found
      describing the degree of laryngeal obstruction by measuring cross-sectional areas
      of the inspiratory laryngeal images. A threshold value was set giving the
      diagnosis of EI-VCD, with a sensitivity of 0.65, a specificity of 0.96, a
      positive-predictive value of 0.79, and a negative-predictive value of 0.93. The
      threshold set for diagnosing EIL gave sensitivity, specificity, positive and
      negative-predictive value of 1.00. EIL and EI-VCD show different objective
      findings confirming that they are two separate conditions both causing laryngeal
      obstruction. The use of the CLE test is mandatory, because this is the only way
      to differ between the two conditions and EILOMEA gives the diagnosis and the
      degree of obstruction objectively.

PMID- 19844736
TI  - Ocular surface inflammation, and nerve growth factor level in tears in active
      thyroid-associated ophthalmopathy.
AB  - PURPOSE: To measure tear nerve growth factor (NGF) concentrations in cases of
      active thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid
      treatment, and to correlate NGF levels with disease inflammatory activity and
      thyroid autoantibody concentration. METHODS: The study involved 20 patients with
      active TAO and 20 age- and gender-matched controls. Tear break-up time (BUT) was
      obtained, the Schirmer test was performed, and tear NGF/total protein ratio was
      measured in control subjects and patients with active TAO before, and 2 and 4
      weeks after, steroid treatment. RESULTS: Tear BUT and Schirmer values
      significantly increased after 2 and 4 weeks of steroid treatment (p < 0.001 and p
      = 0.004 respectively). Baseline tear NGF/total protein ratio was higher in
      patients with active TAO than in control subjects, and the ratio significantly
      decreased after 2 and 4 weeks of steroid treatment (p < 0.001). Tear NGF/total
      protein ratio did not correlate with inflammatory activity score, exophthalmos
      value and thyroid binding inhibiting immunoglobulin (TBII) level (p > 0.05).
      CONCLUSIONS: Tear NGF may have a specific role in ocular surface inflammation,
      which protects against ocular surface damage in patients with active TAO. Anti
      inflammatory treatment significantly reduced the level of NGF in tears, increased
      tear film stability and production, and decreased congestive symptoms.

PMID- 19844737
TI  - Melanoma progression exhibits a significant impact on connexin expression
      patterns in the epidermal tumor microenvironment.
AB  - Melanoma depends on, interacts with and reacts to the stroma in which it is
      embedded, including fibroblasts, extracellular matrix, endothelial cells and
      immune cells. However, the impact of melanoma on the epidermal tumor
      microenvironment-the multilayered epithelium of the skin-is poorly understood.
      Gap junctions are essential for intercellular communication and involved in
      proliferation, differentiation and homeostasis of keratinocytes. We have shown
      previously that the gap junction proteins connexin 26 and 30 (Cx26 and Cx30) are
      induced in the epidermal tumor microenvironment of skin cancers including
      melanoma. This study compares the extent of Cx26, Cx30 and Cx43 expression in the
      epidermal microenvironment of melanocytic nevi and melanomas and its association
      with melanoma thickness, proliferative index of the tumor and its
      microenvironment, and with 5-year metastasis and survival. We found that
      induction of Cx26 and Cx30 cell-cell border expression in the epidermal tumor
      microenvironment correlates to malignancy. Importantly, there was a significant
      correlation of tumor thickness with the vertical epidermal Cx26 and Cx30
      expression pattern and the horizontal Cx26 dissemination. Furthermore, horizontal
      Cx26 expression correlated with metastasis. Vertical epidermal expression
      patterns of Cx26 and Cx30 significantly correlated with the proliferative index
      in the epidermal tumor microenvironment but not with the proliferative index in
      the tumor. In contrast, Cx43 did not correlate with malignancy, thickness or
      proliferative index. In summary, here we show for the first time a significant
      association between the progression of melanoma and alterations in its epithelial
      tumor microenvironment.

PMID- 19844738
TI  - Biologically plausible learning in neural networks: a lesson from bacterial
      chemotaxis.
AB  - Learning processes in the brain are usually associated with plastic changes made
      to optimize the strength of connections between neurons. Although many details
      related to biophysical mechanisms of synaptic plasticity have been discovered, it
      is unclear how the concurrent performance of adaptive modifications in a huge
      number of spatial locations is organized to minimize a given objective function.
      Since direct experimental observation of even a relatively small subset of such
      changes is not feasible, computational modeling is an indispensable investigation
      tool for solving this problem. However, the conventional method of error back
      propagation (EBP) employed for optimizing synaptic weights in artificial neural
      networks is not biologically plausible. This study based on computational
      experiments demonstrated that such optimization can be performed rather
      efficiently using the same general method that bacteria employ for moving closer
      to an attractant or away from a repellent. With regard to neural network
      optimization, this method consists of regulating the probability of an abrupt
      change in the direction of synaptic weight modification according to the temporal
      gradient of the objective function. Neural networks utilizing this method
      (regulation of modification probability, RMP) can be viewed as analogous to
      swimming in the multidimensional space of their parameters in the flow of
      biochemical agents carrying information about the optimality criterion. The
      efficiency of RMP is comparable to that of EBP, while RMP has several important
      advantages. Since the biological plausibility of RMP is beyond a reasonable
      doubt, the RMP concept provides a constructive framework for the experimental
      analysis of learning in natural neural networks.

PMID- 19844739
TI  - Serotonergic mechanisms on breathing modulation in the rat locus coeruleus.
AB  - The locus coeruleus (LC) is a noradrenergic nucleus that plays an important role
      in the ventilatory response to hypercapnia. This nucleus is densely innervated by
      serotonergic fibers and contains high density of serotonin (5-HT) receptors,
      including 5-HT(1A) and 5-HT(2). We assessed the possible modulation of
      respiratory response to hypercapnia by 5-HT, through 5-HT(1A) and 5-HT(2)
      receptors, in the LC. To this end, we determined the concentrations of 5-HT and
      its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) in the LC after hypercapnic
      exposure. Pulmonary ventilation (VE: , plethysmograph) was measured before and
      after unilateral microinjection (100 nL) of WAY-100635 (5-HT(1A) antagonist, 5.6
      and 56 mM), 8-OHDPAT (5-HT(1A/7) agonist, 7 and 15 mM), Ketanserin (5-HT(2A)
      antagonist, 3.7 and 37 mM), or (+/-)-2,5-dimethoxy-4-iodoamphetaminehydrochloride
      (DOI; 5-HT(2A) agonist, 6.7 and 67 mM) into the LC, followed by a 60-min period
      of 7% CO(2) exposure. Hypercapnia increased 5-HTIAA levels and 5-HIAA/5-HT ratio
      within the LC. WAY-100635 and 8-OHDPAT intra-LC decreased the hypercapnic
      ventilatory response due to a lower tidal volume. Ketanserin increased CO(2)
      drive to breathing and DOI caused the opposite response, both acting on tidal
      volume. The current results provide evidence of increased 5-HT release during
      hypercapnia in the LC and that 5-HT presents an inhibitory modulation of the
      stimulatory role of LC on hypercapnic ventilatory response, acting through
      postsynaptic 5-HT(2A) receptors in this nucleus. In addition, hypercapnic
      responses seem to be also regulated by presynaptic 5-HT(1A) receptors in the LC.

PMID- 19844740
TI  - Genome-scale approaches to the epigenetics of common human disease.
AB  - Traditionally, the pathology of human disease has been focused on microscopic
      examination of affected tissues, chemical and biochemical analysis of biopsy
      samples, other available samples of convenience, such as blood, and noninvasive
      or invasive imaging of varying complexity, in order to classify disease and
      illuminate its mechanistic basis. The molecular age has complemented this
      armamentarium with gene expression arrays and selective analysis of individual
      genes. However, we are entering a new era of epigenomic profiling, i.e., genome
      scale analysis of cell-heritable nonsequence genetic change, such as DNA
      methylation. The epigenome offers access to stable measurements of cellular state
      and to biobanked material for large-scale epidemiological studies. Some of these
      genome-scale technologies are beginning to be applied to create the new field of
      epigenetic epidemiology.

PMID- 19844741
TI  - Localization of indoleamine 2,3-dioxygenase in human esophageal squamous cell
      carcinomas.
AB  - Immunosuppressive factors derived from the tumor and nontumor cells present in
      the tumor microenvironment contribute to tumor escape from host immune attack.
      Recently, the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO)
      derived from both the tumor cells and surrounding nontumor cells was found to
      function as a critical immunosuppressive factor. While the expression of IDO is
      intensively under investigation in many types of cancers, little information is
      available in esophageal squamous cell carcinomas (ESCC) thus far. In this study,
      we have therefore investigated the cellular localization of IDO in 45 ESSCs and
      ten morphologically normal esophageal tissues; the correlation of IDO with
      clinicopathological parameters was also analyzed. Immunohistochemistry (IHC)
      analysis revealed that the density of IDO-positive cells was increased in ESCCs
      relative to controls (P < 0.01). These cells were distributed as clusters and
      formed a patchy pattern in both the cancerous epithelium and the surrounding
      noncancerous cells. Double IHC further confirmed that many IDO-positive cells in
      the tumor stroma were smooth-muscle-actin-alpha-positive myofibroblasts, CD68
      positive macrophages, and S100-positive dendritic cells. Statistical analysis
      showed that the densities of IDO-positive cells were not significantly correlated
      with tumor clinical parameters (tumor invasion depth, node metastasis, and TNM
      stages) and lymphocytic infiltration. Our current findings suggested that the
      increased IDO expression in ESCCs is from a mixed cellular source (both cancer
      cells and noncancerous cells). Further studies on immune cell functional analysis
      are required in the future.

PMID- 19844742
TI  - Analysis of the structure of the brain stem of mammals by means of a modified
      D'Arcy Thompson procedure.
AB  - In his famous book, 'On Growth and Form', D'Arcy Thompson demonstrated that the
      shapes of related animals, or parts thereof, can be transformed into each other
      by a simple graphical procedure, called the method of coordinates. In this
      procedure, an object is inscribed in a net of Cartesian coordinates. It appeared
      that the shape of related objects could be characterized by means of simple,
      harmonious deformations of the initial orthogonal system of coordinates. Here, I
      demonstrate that: (1) the central nervous system contains a built-in, natural
      coordinate system; (2) differences in shape and proportion of cross sections
      through the brain stem of various mammals can be easily analyzed with the aid of
      this coordinate system, and (3) sets of structures in the mammalian brain stem,
      which are closely related to the neocortex, but form part of entirely different
      functional systems, form spatially constrained complexes, and have the capacity
      to expand jointly and harmoniously within these complexes.

PMID- 19844743
TI  - Ultrastructure and host parasite relationships of Kudoa pagrusi (Myxozoa)
      infecting the heart muscles of sea bream Pagrus pagrus (L.) from the Red Sea.
AB  - The present study is a part of a continuous investigation of myxosporean
      parasites-infecting fish of the Red Sea using light and electron microscopy. Out
      of 120, 80 (67%) Pagrus pagrus fish were found to be naturally infected with
      Kudoa pagrusi. The infection was intensive and appeared as clusters of ovoid to
      ellipsoidal plasmodia being restricted to the cardiac muscles. Histological
      studies elaborated tissue distortion at the sites of infection and the adjacent
      layers. The development of the plasmodia reduced the functional area of the heart
      muscle. Ultrastructural analysis showed that the plasmodia were surrounded by
      single-unit membrane with numerous projections and pinocytotic channels extended
      toward the host cell. The generative cells and the different developmental stages
      were arranged at the periphery of the plasmodia while immature and mature spores
      were centrally arranged. The present study showed the main criteria of this
      genus: the spores possess four polar capsules with four shell valves.

PMID- 19844744
TI  - Ultrastructure, development, and host-parasite relationship of a new species of
      the genus Pleistophora--a microsporidian parasite of the marine fish Epinephelus
      chlorostignei.
AB  - The life cycle of a new microsporidian of the genus Pleistophora is described.
      This parasite infects the epithelial cells of the gut and the peritoneal cavity
      of the Red Sea fish, Epinephelus chlorostignei. All stages develop within a
      special structure, the sporophorocyst, which is covered by a thick dense wall.
      This wall grows along with the growth of the parasites inside. Meronts are uni-
      to binucleate, which divide and constantly give rise to sporonts. During
      transition to sporonts, the cell border of the meronts increases its thickness,
      temporarily featuring thick irregular projections. Eventually, a uniform thick
      sporont wall is formed; then, the sporont cells detach themselves from the wall
      (future wall of the sporophorous vesicle, SPV) and start a series of divisions to
      produce sporoblasts. The SPV wall is compact, has no pores, and consists of two
      layers. Mature spores measure about 2.0 x 1.8 microm. They possess a polar
      filament with 20-28 coils, a posterior vacuole, and a polaroplast made up of an
      outer part of dense and closely spaced lamellae encircling an inner part of
      widely spaced lamellae. All morphological and ultrastructural features indicate
      that the described microsporidian parasite belongs to the genus Pleistophora.

PMID- 19844745
TI  - An infant with orange-colored urine.

PMID- 19844746
TI  - Effects of steroid avoidance and novel protocols on growth in paediatric renal
      transplant patients.
AB  - The vast majority of kidney transplant recipients undergo triple maintenance
      immunosuppression that includes the use of steroids. Irrespective of their long
      history in organ transplantation and proven efficacy in preventing acute graft
      rejection, steroids exhibit an unfavourable toxicity profile, including growth
      retardation in children. Given these negative effects, therapeutic approaches
      that will substantially decrease patients' exposure to steroids have been
      considered. The planned approaches included alternate day administration, rapid
      or late steroid withdrawal at the pre-scheduled time after transplantation and
      complete steroid avoidance. All three of these strategies have been tested in
      single- or multicentre studies and shown to have distinct clinical advantages in
      terms of decreasing the incidence and severity of specific adverse events.
      However, the safety of these protocols could not be universally proven. The
      Stanford study showed that a complete steroid avoidance under the "cover" of
      tacrolimus, mycophenolate mofetil and extended daclizumab induction is a very
      effective regimen for obtaining an improvement in post-transplantation growth.
      The recently reported international randomized TWIST trial demonstrated growth
      improvement as early as 6 months post-transplantation. These protocols may
      potentially enable paediatric renal graft recipients to safely avoid steroid
      exposure.

PMID- 19844747
TI  - Mechanisms of renal injury and progression of renal disease in congenital
      obstructive nephropathy.
AB  - Congenital obstructive nephropathy accounts for the greatest fraction of chronic
      kidney disease in children. Genetic and nongenetic factors responsible for the
      lesions are largely unidentified, and attention has been focused on minimizing
      obstructive renal injury and optimizing long-term outcomes. The cellular and
      molecular events responsible for obstructive injury to the developing kidney have
      been elucidated from animal models. These have revealed nephron loss through
      cellular phenotypic transition and cell death, leading to the formation of
      atubular glomeruli and tubular atrophy. Altered renal expression of growth
      factors and cytokines, including angiotensin, transforming growth factor-beta,
      and adhesion molecules, modulate cell death by apoptosis or phenotypic transition
      of glomerular, tubular, and vascular cells. Mediators of cellular injury include
      hypoxia, ischemia, and reactive oxygen species, while fibroblasts undergo
      myofibroblast transformation with increased deposition of extracellular matrix.
      Progression of the lesions involves interstitial inflammation and interstitial
      fibrosis, both of which impair growth of the obstructed kidney and result in
      compensatory growth of the contralateral kidney. The long-term outcome depends on
      timing and severity of the obstruction and its relief, minimizing ongoing injury,
      and enhancing remodeling. Advances will depend on new biomarkers to evaluate the
      severity of obstruction, to determine therapy, and to follow the evolution of
      lesions.

PMID- 19844749
TI  - Langerhans cell histiocytosis of the atlas in an adult.
AB  - Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is a rare
      disorder (approximately 1:1,500,000 inhabitants) characterized by clonal
      proliferation and excess accumulation of pathologic Langerhans cells causing
      local or systemic effects. The exact etiology of LCH is still unknown. LCH could
      affect patients of any age, although most present when they are children. The
      most frequent sites of the bony lesions are the skull, femur, mandible, pelvis
      and spine. A variety of treatment modalities has been reported, but there was no
      evidence suggesting that any one treatment was more advantageous than another. We
      present an adult with LCH of the atlas. A 26-year-old young man presented with a
      2-month history of neck pain and stiffness. CT revealed osteolytic lesion in the
      left lateral mass of atlas with compression fracture. Histopathological diagnosis
      was Langerhans cell histiocytosis by percutaneous needle biopsy under CT
      guidance. The patient underwent conservative treatment, including Halo-vest
      immobilization and radiotherapy. At 7-year follow-up, the patient was
      asymptomatic except for mild motion restriction of the neck. CT revealed a
      significant reconstruction of the C1 lateral mass.

PMID- 19844748
TI  - Large vessel vasculitis.
AB  - Takayasu arteritis is a chronic granulomatous disease of the aorta and its major
      branches that usually affects women during the second and third decades of life,
      but it has been reported in young children. This review details the clinical,
      pathological and radiological features, differential diagnoses and management of
      the condition, focusing chiefly on the disease in children. The recent definition
      of Takayasu arteritis is discussed. The condition should be considered in
      patients with unexplained arterial hypertension or unexplained inflammatory
      syndromes without signs of localization. Since the disease may be life
      threatening and progressive, early recognition is necessary to initiate
      appropriate therapy. Patients with persistent ischaemic symptoms including
      hypertension might benefit from revascularization procedures.

PMID- 19844750
TI  - Cost-effectiveness of infliximab for the treatment of acute exacerbations of
      ulcerative colitis.
AB  - BACKGROUND: Infliximab has been shown to be efficacious in acute exacerbations of
      ulcerative colitis (UC). AIM: To evaluate the cost-effectiveness of infliximab
      treatment in patients hospitalised with acute exacerbations of UC. METHODS: A
      decision analysis model was constructed to simulate the progression of acute UC
      patients treated with infliximab induction regimen over 1 year. Infliximab
      treatment was compared with standard care, ciclosporin and surgery using
      transitions derived from infliximab and ciclosporin randomised trials. Costs and
      outcomes were discounted at 3.5%. Intermediate outcomes of colectomy and post
      surgery complications were translated into the primary effectiveness measurement,
      which was quality-adjusted life years (QALYs) estimated using EQ-5D. One-way and
      probabilistic sensitivity analyses were performed to estimate the uncertainty
      around the results. RESULTS: The incremental cost effectiveness ratio (ICER) for
      infliximab was pound19,545 per QALY compared to ciclosporin, which in turn
      dominated standard care. Sensitivity analysis indicated patient body weight,
      utility estimates and treatment effect of alternative treatment strategies to be
      the most important factors affecting cost-effectiveness. CONCLUSION: Infliximab
      induction regimen appears to be a cost-effective treatment option for UC patients
      hospitalised with an acute exacerbation.

PMID- 19844751
TI  - Pediocin production in milk by Pediococcus acidilactici in co-culture with
      Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus.
AB  - The production of pediocin in milk by Pediococcus acidilactici was evaluated in
      co-culture with the dairy fermentation cultures Streptococcus thermophilus and
      Lactobacillus delbrueckii ssp. bulgaricus. The cultures were tested singly and in
      different combinations in milk (0 or 2% fat content) during incubation at 40
      degrees C for up to 10 h. Cell-free milk samples taken every 60 min were tested
      for bacteriocin activity against Listeria monocytogenes. Pediocin activity was
      not detectable when P. acidilactici was inoculated into milk as a monoculture.
      When P. acidilactici was grown in combination with the yogurt starter cultures S.
      thermophilus and Lb. delbrueckii ssp. bulgaricus, pediocin concentration reached
      3,200-6,400 units ml(-1) after 8 h of incubation. The results showed that
      pediocin producing pediococci may be useful adjunct components in mixed cultures
      of S. thermophilus and Lb. delbrueckii ssp. bulgaricus to amplify the
      bioprotective properties of fermented dairy foods against Listeria contamination.

PMID- 19844752
TI  - Formation of shaped barium sulfate-dye hybrids: waste dye utilization for eco
      friendly treatment of wastewater.
AB  - PURPOSE: Owing to the present complexity and difficulty of concentrated dye
      wastewater treatment, this work aimed to synthesize a reproducible waste-sorbing
      material for the treatment of wastewater by forming the dye-conjugating complex
      hybrid. METHODS: The inorganic/organic hybridization was applied to prepare the
      objective material by immobilizing waster dye-Mordant blue 9 (MB) with barium
      sulfate (BaSO4). The composition and pattern of the formed material were
      determined by spectrometry and characterized by SEM and XRD, and their formation
      process was clarified. The adsorption of cationic dye-basic blue BO (BB) and
      copper ion was investigated. RESULTS: The hybrid of MB alone into growing BaSO4
      formed the pineapple-like particles while that of the MB/BB-conjugating complex
      was the rhombus material. The adsorption of BB on the MB-BaSO4 hybrid was
      probably attributed to ion-pair equilibrium and that of Cu2+ may result from the
      complexation. The treatment of dye and heavy metal wastewaters indicated that the
      MB hybrid material removed 99.8% BB and 97% Cu2+ and the dye-conjugating hybrid
      with growing BaSO4 100% MB, 99.5% BB, and 44% Cu2+. CONCLUSION: The waste MB
      BaSO4 hybrid material is efficient to treat cationic dye and Cu2+ wastewater. The
      dye-conjugating hybridization method is the first to be advanced for in situ
      wastewater treatment, and it showed a combined effect for the removal of both
      organic dyes and heavy metals.

PMID- 19844753
TI  - Associations between lactase persistence and the metabolic syndrome in a cross
      sectional study in the Canary Islands.
AB  - BACKGROUND: The single nucleotide polymorphism (SNP) LCT -13910 C>T, associated
      with genetically determined phenotypes of lactase persistence (LP) or non
      persistence (LNP), was studied in relation to the metabolic syndrome (MS). AIM OF
      THE STUDY: The aim was to determine if milk intake and MS are associated. We
      applied Mendelian randomization (MR). The SNP, LCT -13910 C>T, with the genotypes
      LP (TT/CT) and LNP (CC), was taken as a proxy for milk consumption. METHODS: A
      representative sample of adults belonging to the Canary Islands Nutrition Survey
      (ENCA) in Spain aged 18-75 years (n = 551) was genotyped for the LCT -13910 C>T
      polymorphism. We used the International Diabetes Federation (IDF) criteria to
      define MS. RESULTS: 60% of the population was LP and 40% LNP. One hundred seven
      LP subjects (35.0%) and 53 LNP subjects (25.6%) showed MS (chi (2) = 5.04, p =
      0.025). LP subjects showed a significantly higher odds ratio (OR) for MS than LNP
      subjects computed for the whole population: both the crude OR (1.56; 95% CI 1.06
      2.31) and adjusted OR for sex, age, daily energy intake, physical activity and
      educational level (1.57; 95% CI 1.02-2.43). Adjusted OR for women with LP was
      1.93; 95% CI 1.06-3.52. CONCLUSIONS: The T allele of the SNP might constitute a
      nutrigenetic factor increasing the susceptibility of LP subjects, especially
      women, to develop MS in the Canary Islands.

PMID- 19844754
TI  - Monoamines, BDNF, IL-6 and corticosterone in CSF in patients with Parkinson's
      disease and major depression.
AB  - The biochemical basis of major depression (MD) in Parkinson's disease (PD) is
      largely unknown. To increase our understanding of MD in PD patients, the levels
      of monoamine metabolites (HVA, 5-HIAA and MHPG), BDNF, orexin-A, IL-6 and
      corticosterone were examined in cerebrospinal fluid. The analyses were performed
      in MD patients with (n = 11) and without (n = 12) PD at baseline and after 12
      weeks' of treatment with the antidepressant citalopram, and in patients with
      solely PD (n = 14) at baseline and after 12 weeks. The major findings were that
      PD patients with MD had significantly lower baseline levels of MHPG,
      corticosterone and IL-6 when compared to patients with solely MD. In response to
      citalopram treatment, patients with solely MD exhibited an expected decrease in 5
      HIAA and MHPG levels which was not found in PD patients with MD. Moreover, the
      levels of BDNF and IL-6 were lower in PD patients with MD compared with patients
      with solely MD after treatment with citalopram. Thus, the biochemical basis and
      the response to citalopram differ between PD patients with MD and patients with
      solely MD.

PMID- 19844755
TI  - Renal cell carcinoma: real-time contrast-enhanced ultrasound findings.
AB  - OBJECTIVE: To investigate the findings of renal cell carcinomas (RCCs) on
      contrast-enhanced ultrasound (CEUS). METHODS: CEUS features of 84 RCCs confirmed
      by pathologic examination in 81 patients were retrospectively analyzed. A
      contrast-specific mode and a sulfur hexafluoride-filled microbubble contrast
      agent were used for CEUS. The enhancement pattern, extent, and dynamic change in
      the cortical, corticomedullary, and late phases were evaluated. RESULTS: On CEUS,
      the emergence of tumor enhancement was earlier in two nodules (2.4%),
      simultaneous in 71 (84.5%), and later in 11 (13.1%), in comparison with the
      adjacent renal cortex. Seventy-four RCC nodules (88.1%) showed hyper-enhancement
      (n = 2) or iso-enhancement (n = 72) during the cortical phase, and the remaining
      10 (11.9%) showed hypo-enhancement. Twenty-three nodules (27.4%) showed
      homogeneous enhancement and 61 (72.6%) inhomogeneous enhancement. In the
      corticomedullary phase, the nodules showed hypo-enhancement in 68 (81.0%) and iso
      enhancement in 16 (19.0%). In the late phase, all RCCs showed the same
      enhancement pattern as that shown in the corticomedullary phase. Seventy-two
      (85.7%) nodules showed a clear perilesional rim-like enhancement in late phase.
      CONCLUSIONS: Hyper- or iso-enhancement during the cortical phase, subsequent
      washout in late phase, inhomogeneous enhancement, and perilesional rim-like
      enhancement are clues for RCCs, which might be useful for characterization of
      RCCs.

PMID- 19844757
TI  - Effect of smoking on cough reflex sensitivity: basic and preclinical studies.
AB  - In healthy nonsmokers, inhalation of one single puff of cigarette smoke
      immediately evoked airway irritation and cough, which were either prevented or
      markedly diminished after premedication with hexamethonium. Single-fiber
      recording experiments performed in anesthetized animals showed that both C fibers
      and rapidly adapting receptors in the lungs and airways were stimulated by
      inhalation of one breath of cigarette smoke. Application of nicotine evoked an
      inward current and triggered depolarization and action potentials in a
      concentration-dependent manner in a subset of isolated vagal pulmonary sensory
      neurons. Taken together, these studies showed that activation of the nicotinic
      acetylcholine receptors expressed on airway sensory nerves is mainly responsible
      for the acute airway irritation and cough reflex elicited by inhaled cigarette
      smoke. Chronic exposure to cigarette smoke consistently induces enhanced cough
      responses to various inhaled tussive agents in guinea pigs. The increased cough
      sensitivity involves primarily an elevated sensitivity of cough sensors and also
      an enhanced synaptic transmission of their afferent signals at the nucleus
      tractus solitaries. In contrast to the observations in animal studies, both
      enhanced and diminished cough sensitivities to tussive agents have been reported
      in chronic smokers. This discrepancy is probably related to the history of
      chronic smoking of the individual smokers and the severity of existing airway
      inflammation and dysfunction. Furthermore, several other factors possibly
      contributing to the regulation of cough receptor sensitivity in chronic smokers
      should also be considered.

PMID- 19844758
TI  - Can we improve sleep quality by changing the way we ventilate patients?

PMID- 19844759
TI  - Design and performance of a turbot (Scophthalmus maximus) oligo-microarray based
      on ESTs from immune tissues.
AB  - An expressed sequence tag database from immune tissues was used to design the
      first high-density turbot (Scophthalmus maximus) oligo-microarray with the aim of
      identifying candidate genes for tolerance to pathogens. Specific oligonucleotides
      (60 mers) were successfully designed for 2,716 out of 3,482 unique sequences of
      the database. An Agilent custom oligo-microarray 8 x 15 k (five replicates/gene;
      eight microarrays/slide) was constructed. The performance of the microarray and
      the sources of variation along microarray analysis were examined on spleen pools
      of controls and Aeromonas salmonicida-challenged fish at 3 days postinfection.
      Only 48 out of 2,716 probes did not show signal of hybridization on the 32
      microarrays employed, thus demonstrating the consistency of the bioinformatic
      applications of our database. An asymmetric hierarchical design was employed to
      ascertain the noise associated with biological and technical (RNA extraction,
      labeling, hybridization, slide, and dye bias) factors using 1C and 2C labeling
      approaches. The high correlation coefficient between replicates at most factors
      tested demonstrated the high reproducibility of the signal. An analysis of random
      effects variance revealed that technical variation was mostly negligible, and
      biological variation represented the main factor, even using pooled samples. One
      color approach performed at least as well as 2C, suggesting their usefulness due
      to its higher design flexibility and lower cost. A relevant proportion of genes
      turn out to be differentially labeled depending on fluorophore, which alerts for
      the likely need of swapping replication in 2C experiments. A set of
      differentially expressed genes and enriched functions related to immune/defense
      response were detected at 3 days postchallenging.

PMID- 19844760
TI  - Prothoracic gland semiochemicals of green lacewings.
AB  - Adult chrysopids have paired prothoracic glands (PG) that are thought to produce
      defensive secretions (allomones). We analyzed PG extracts of the following green
      lacewings from North and South America, Australia, and China: Ceraeochrysa cubana
      (Brazil); Chrysopa (= Co.) oculata, Co. nigricornis, Co. incompleta, Co.
      quadripunctata (USA), and Co. septempunctata (China); Chrysoperla (= Cl.)
      rufilabris (USA) and Cl. sp. (Brazil); Plesiochrysa ramburi and Mallada spp.
      (Australia). PG secretions are characteristic for species within a genus, except
      for Chrysopa spp. (Z)-4-Tridecene is ubiquitous, but (Z,Z)-4,7-tridecadiene is a
      major PG constituent in some Chrysopa spp. and in P. ramburi. Earlier reports
      that Co. oculata and Co. nigricornis produce 1-tridecene were shown to be in
      error. Chrysopa PG secretions are distinguished by the presence or absence of N-3
      methylbutylacetamide, plus skatole (3-methylindole). Skatole is also identified
      for the first time from the Plesiochrysa and Ceraeochrysa. The PG secretion in
      Plesiochrysa ramburi is characterized by the presence of (Z)-4-undecene instead
      of (Z)-4-tridecene, and N-3-methylbutylpropanamide instead of the acetamide,
      resembling the PG secretions of Chrysopa nigricornis, Co. septempunctata and Co.
      incompleta. The chemotaxonomic value of PG semiochemicals is discussed, including
      evidence for subgroups within the genus Chrysopa as it now stands.

PMID- 19844762
TI  - Lymphadenectomy in gastric cancer: the controversy refuses to die.

PMID- 19844763
TI  - General practitioners' judgment of their elderly patients' cognitive status.
AB  - BACKGROUND: General practitioners (GP) play an important role in detecting
      cognitive impairment among their patients. OBJECTIVES: To explore factors
      associated with GPs' judgment of their elderly patients' cognitive status.
      DESIGN: Cross-sectional data from an observational cohort study (AgeCoDe study);
      General practice surgeries in six German metropolitan study centers; home visits
      by interviewers. PARTICIPANTS: 138 GPs, 3,181 patients (80.13 +/- 3.61 years,
      65.23% female). MEASUREMENTS: General practitioner questionnaire for each
      patient: familiarity with the patient, patient morbidity, judgment of cognitive
      status. Home visits by trained interviewers: sociodemographic and clinical data,
      psychometric test performance. Multivariate regression analysis was used to
      identify independent associations with the GPs' judgment of "cognitively
      impaired" vs. "cognitively unimpaired." RESULTS: Less familiar patients (adjusted
      odds ratio [aOR] 2.42, 95% CI 1.35-4.32, for poor vs. very high familiarity),
      less mobile patients (aOR 1.29, 95% CI 1.13-1.46), patients with impaired hearing
      (aOR 5.46, 95% CI 2.35-12.67 for serious vs. no problems), and patients with
      greater comorbidity (aOR 1.15, 95% CI 1.08-1.22) were more likely to be rated as
      "cognitively impaired" by their GPs. CONCLUSIONS: The associations between GPs'
      assessments of cognitive impairment and their familiarity with their patients and
      patients' mobility, hearing, and morbidity provide important insights into how
      GPs make their judgments.

PMID- 19844764
TI  - Sleeve gastrectomy for childhood morbid obesity: why not?

PMID- 19844765
TI  - Bariatric surgery in the management of childhood obesity: should there be an age
      limit?
AB  - We report a case of a 6-year-old girl suffering from morbid obesity, Blount;s
      disease, and significant social and functional impairment who underwent a
      laparoscopic sleeve gastrectomy. One year later, she has shown remarkable
      improvement in all aspects of her health emphasizing the success of the
      procedure. A follow-up laparoscopic Roux-en-Y gastric bypass or biliopancreatic
      diversion (BPD) are options if she regains weight as she gets older. This case is
      noteworthy for several reasons. The age of the patient is younger than any
      currently on record who has had this treatment. Additionally, the utilization of
      a sleeve gastrectomy as a first-step procedure, to be followed by Roux-en-Y
      gastric bypass or BPD, remains a novel treatment for morbid obesity in a
      pediatric population.

PMID- 19844766
TI  - Response from Dilip Dan to Commentary from Inge on Case Report OBSU-D-09-00159.

PMID- 19844767
TI  - 50 years ago in CORR: Arthrodesis of the knee joint. F. H. Moore and I. S.
      Smillie. CORR;13:215-221.

PMID- 19844768
TI  - Discontinuation of warfarin is unnecessary in total knee arthroplasty.
AB  - Patients with medical comorbidities that necessitate chronic anticoagulation
      therapy frequently present as candidates for total knee arthroplasty (TKA). We
      asked whether it was necessary to stop warfarin preoperatively to avoid
      postoperative bleeding complications. We retrospectively reviewed 77
      preoperatively anticoagulated patients undergoing TKA. Thirty-eight of these 77
      patients were maintained on their routine therapeutic warfarin regimen throughout
      the perioperative period. The remaining 39 patients had their routine
      preoperative warfarin regimen discontinued preoperatively and then restarted
      after surgery. We compared rates of comorbid illness, blood transfusions, wound
      complications, and reoperations. The demographic data and the ratio of primary to
      revision arthroplasties were similar in the two groups. The age-adjusted risk
      ratios for blood transfusions, wound complications, and reoperations were 0.61,
      0.29, and 0.43, respectively. The data presented suggest maintaining a
      therapeutic warfarin regimen throughout the perioperative period for high-risk
      patients is not associated with an increase risk of complications after TKA.
      LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 19844769
TI  - Editorial: a paucity of women among residents, faculty, and chairpersons in
      orthopaedic surgery.

PMID- 19844770
TI  - The outerbridge classification predicts the need for patellar resurfacing in TKA.
AB  - Patellar resurfacing (PR) in total knee arthroplasty (TKA) is controversial. The
      Outerbridge classification of cartilage defects in the patella is commonly used
      in the literature. The purpose of this study was to determine if the Outerbridge
      classification can predict the need for PR as part of total knee arthroplasty.
      Between 1995 and 2000, we performed a prospective, randomized study of 500 TKAs.
      We carried out PR depending on the Outerbridge classification of the patella at
      the time of surgery. Patients with Outerbridge Grades I, II, and III formed Group
      A, whereas patients with Grade IV formed Group B. Within each group, resurfacing
      was completed on half of the patients. Group A had 328 patients (164 with PR, 164
      without PR). In Group B, there were 172 patients (86 with PR, 86 without PR). An
      identical prosthetic design was used for both groups. The minimum followup was 5
      years (average, 7.8 years) for both Group A and Group B. At the end of followup,
      we assessed the number of patients in each group that required secondary
      resurfacing as a result of patellofemoral pain. Patients in Group A required
      fewer revisions for PF pain. In Group A, only one patient required a secondary PR
      (0.6% rate), whereas in Group B, 10 patients needed PR (11.6% rate). In Group B,
      the risk of need of a patellar resurfacing was 21.5 times greater than in Group
      A. On the basis of these findings, we recommend PR in Outerbridge Grade IV
      patellae, but not in Grades I, II, and III. LEVEL OF EVIDENCE: Level II,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 19844771
TI  - Biographical sketch: Nathaniel Allison, 1876-1932.
AB  - This biographical sketch of Nathaniel Allison corresponds to the historic text,
      The Classic: Symposium on Arthroplasty: Arthroplasty: Experimental and Clinical
      Methods, available at DOI 10.1007/s11999-009-1120-3 .

PMID- 19844772
TI  - Patient satisfaction after total knee arthroplasty: who is satisfied and who is
      not?
AB  - Despite substantial advances in primary TKA, numerous studies using historic TKA
      implants suggest only 82% to 89% of primary TKA patients are satisfied. We
      reexamined this issue to determine if contemporary TKA implants might be
      associated with improved patient satisfaction. We performed a cross-sectional
      study of patient satisfaction after 1703 primary TKAs performed in the province
      of Ontario. Our data confirmed that approximately one in five (19%) primary TKA
      patients were not satisfied with the outcome. Satisfaction with pain relief
      varied from 72-86% and with function from 70-84% for specific activities of daily
      living. The strongest predictors of patient dissatisfaction after primary TKA
      were expectations not met (10.7x greater risk), a low 1-year WOMAC (2.5x greater
      risk), preoperative pain at rest (2.4x greater risk) and a postoperative
      complication requiring hospital readmission (1.9x greater risk). LEVEL OF
      EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19844773
TI  - Bioassay-guided separation of the proinflammatory constituents from the roots of
      Euphorbia kansui.
AB  - In view of the toxic inflammatory reaction induced by Euphorbia kansui roots, a
      traditional Chinese medicine used for the treatment of edema, ascites, and
      asthma, the 95% ethanol extract was found to have a significant stimulating
      effect on inflammatory cells. Bioassay-guided separation of the 95% ethanol
      extract from the roots of E. kansui led to the isolation of five diterpenoids
      whose structures were identified by (1)H, (13)C NMR spectroscopy and HR-ESI-MS as
      kansuinine B (1), kansuinine A (2), kansuiphorin C (3), 3-O-benzoyl-20
      deoxyingenol (4), and 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5). The
      proinflammatory effect of compounds 1-5 was evaluated in vitro in models of
      inflammation using exoteric mice splenic lymphocytes (SPL) and rat peritoneal
      macrophages (PMphi). Compounds 1, 2, and 5 markedly promoted SPL proliferation
      and NO production by PMphi at concentrations from 0.78 to 12.50 microg/mL. Hence
      the three compounds are believed to be important proinflammatory components of
      the roots of E. kansui.

PMID- 19844774
TI  - Forest experience and psychological health benefits: the state of the art and
      future prospect in Korea.
AB  - The aims of this study were twofold: to examine the empirical evidence supporting
      the positive contribution that a forest environment can make on human
      psychological health and well-being and to describe the theoretical framework
      within which the forest environment has this effect. Our review of the literature
      provides empirical evidence that a forest experience can contribute to improved
      emotional and cognitive health.This experience can be through a forest activity
      program and by experiencing the social and physical conditions of the forest
      environment and the therapeutic elements of the forest. Visiting or viewing a
      forest scene has been documented to have a positive effect on psychological
      healing and well-being in terms of recovering from stress, improving
      concentration and productivity, improving the psychological state, particularly
      for people from urban environments. Wilderness and related studies clearly
      demonstrate that being in a forest environment has a positive effect on people,
      while results from other studies indicate that contacts with forest environments
      provide multiple positive physiological and psychological effects on human health
      that included decreasing the blood pressure and heart rate and reducing anxiety
      and stress. There are several theories explaining the healing effects of the
      forest on human beings. Most hypothesize that restorative environments are
      settings in which recovery is associated with the reduction of stress and that
      the benefits of contact with natures include a wide range of positive
      physiological and psychological responses. These theories are based on an
      evolutionary perspective and share a number of similarities and differences. This
      article summarizes a number of these theories of restorative environments as well
      as addresses the current status of forest therapy and the challenges and
      opportunities for therapeutic effects of the forest in Korea.

PMID- 19844775
TI  - Expression and distribution of CYP3A genes, CYP2B22, and MDR1, MRP1, MRP2, LRP
      efflux transporters in brain of control and rifampicin-treated pigs.
AB  - The in vivo effect of rifampicin, a potent ligand of PXR, on gene expression of
      CYP2B22, 3A22, 3A29, 3A46, CAR, PXR and MDR1, MRP1, MRP2, LRP transporters in
      liver and cortex, cerebellum, midbrain, hippocampus, meninges and brain
      capillaries of pig was investigated. Animals were treated i.p. with four daily
      doses of rifampicin (40 mg/kg). The basal mRNA expressions of the individual
      CYP3As, CYP2B22, CAR, and PXR in various brain regions, except meninges, were
      about or below 10% of the corresponding hepatic mRNA values, whereas the mRNAs of
      brain transporters were closer or comparable to those in liver. After pig
      treatment with rifampicin, the mRNA expression of CYPs and transporters from
      brain regions did not appear to change, except CYP3A22 and 3A29 in cortex and
      hippocampus, CYP2B22 in meninges. An enzymatic analysis for CYP3As and CYP2B, in
      microsomes and mitochondria from liver and brain tissues using the marker
      activities 7-benzyloxyquinoline O-debenzylase and the anthraldehyde oxidase,
      showed the lack of rifampicin induction in all the brain regions, unlike liver.
      Taken together, our results demonstrate that CYP2B22, CYP3As, and MDR1, MRP1,
      MRP2, and LRP transporters are all expressed, although at different extent, in
      the brain regions but, despite the presence of PXR and CAR, are resistant to
      induction indicating that the regulation of these proteins is more complex in
      brain than in liver. These data obtained in vivo in the brain regions and liver
      of pig may be of interest to human metabolism in CNS.

PMID- 19844776
TI  - Chitosan prevents oxidative stress-induced amyloid beta formation and
      cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF
      kappaB.
AB  - Increased oxidative stress is a widely accepted factor in the development and
      progression of Alzheimer's disease. Here, we introduce chitosan, an antioxidant
      oligosaccharide, as a protective agent against H(2)O(2)/FeSO(4)-induced cell
      death in the NT2 neural cell line. Chitosan not only protects the neurons against
      cell death, as measured by MTT and caspase-3 activity, but also decreases amyloid
      beta formation. NT2 neurons can be used to elucidate the relationship between
      oxidative stress and Abeta formation. We induced Abeta formation through
      oxidative stress in NT2 neurons and studied the effect of chitosan. We
      demonstrate that chitosan can be neuroprotective by suppressing Abeta formation.
      We further show that chitosan exerts its protective effect by up-regulation of HO
      1, gamma-GCS, Hsp-70, and Nrf2, while it inhibits activation of caspase-3 and NF
      kappaB. Chitosan or chitosan derivatives have potential value as neuroprotective
      agents, particularly with regard to oxidative stress.

PMID- 19844777
TI  - Study of the elution of fluconazole from a self-polymerizing acrylic resin and
      its activity against resistant Candida albicans.
AB  - The study aimed, firstly, to monitor the release of an antifungal drug,
      fluconazole, from a self-polymerizing poly(methyl methacrylate) (PMMA) denture
      base resin in artificial saliva and comparing it with the release in water; and
      secondly, to investigate the effect of the released drug on the growth of
      resistant and standard strains of Candida albicans. A high-performance liquid
      chromatography-ultra-violet (HPLC-UV) method was used in the analysis of the
      released eluates into distilled water from self-polymerized PMMA discs doped with
      the 10% fluconazole antifungal drug. The efficacy of the released drug against
      resistant and standard strains of C. albicans was monitored, using agar diffusion
      method. The results showed that fluconazole, can be successfully incorporated
      with the self-polymerized PMMA. The findings suggest that the drug leaches
      steadily out of the PMMA resin into artificial saliva and distilled water at
      mouth temperature and that sustained drug release continued throughout the 28
      days test period. It was shown that the released drug demonstrated antifungal
      activity against both standard and resistant C. albicans. The findings of this
      investigation have a clinical value in terms of their significant contribution to
      the treatment of fungal infections of the oral cavity. The sustained release of
      antifungal drug from the PMMA resin clearly constitutes a new dosage form of the
      drug via the poly(methyl methacrylate) delivery system.

PMID- 19844778
TI  - Exploring workplace actors experiences of the social organization of return-to
      work.
AB  - INTRODUCTION: There is a limited body of research on how the actual social
      exchange among workplace actors influences the practice of return-to-work. The
      objective of this study was to explore how workplace actors experience social
      relations at the workplace and how organizational dynamics in workplace-based
      return-to-work extends before and beyond the initial return of the sick listed
      worker to the workplace. METHOD: An exploratory qualitative method approach was
      used, consisting of individual open-ended interviews with 33 workplace actors at
      seven worksites that had re-entering workers. The workplace actors represented in
      these interviews include: re-entering workers, supervisors, co-workers, and human
      resource managers. RESULTS: The analysis identified three distinct phases in the
      return to work process: while the worker is off work, when the worker returns
      back to work, and once back at work during the phase of sustainability of work
      ability. The two prominent themes that emerged across these phases include the
      theme of invisibility in relation to return-to-work effort and uncertainty,
      particularly, about how and when to enact return-to-work. CONCLUSION: The
      findings strengthen the notion that workplace-based return-to-work interventions
      need to take social relations amongst workplace actors into account. They also
      highlight the importance and relevance of the varied roles of different workplace
      actors during two relatively unseen or grey areas, of return-to-work: the pre
      return and the post-return sustainability phase. Attention to the invisibility of
      return-to-work efforts of some actors and uncertainty about how and when to enact
      return-to-work between workplace actors can promote successful and sustainable
      work ability for the re-entering worker.

PMID- 19844779
TI  - Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) is a multifactorial functional
      gastrointestinal disorder, characterized by recurrent abdominal pain and altered
      bowel habits. Proinflammatory cytokines can play an important role in intestinal
      inflammation, while their production is under genetic control. METHODS: This
      study was performed in a group of patients with IBS to analyze the genotype
      frequencies of a number polymorphic genes coding for proinflammatory cytokine
      (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-alpha), and IL-1 group).
      Using polymerase chain reaction with sequence-specific primers method, the
      cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS
      were detected on gel electrophoresis, and the results were compared with healthy
      control subjects. RESULTS: Results of the analyzed data showed that the
      frequencies IL-1R C allele at position Pst-I 1970 (P = 0.017), IL-6 G allele at
      position -174 (P = 0.002), and TNF-alpha G allele at position -238 (P < 0.001) in
      the patient group were significantly higher than the control group. IL-6 GG
      genotype (-174) and TNF-alpha GG genotype (-238) in the patient group were also
      significantly overrepresented (P < 0.001), while IL-6 CG genotype (-174) and TNF
      alpha GA genotype (-238) were significantly decreased in the patients with IBS (P
      < 0.001). The frequencies of IL-6 (-174, nt565) GG haplotype and TNF-alpha (-308,
      -238) GG haplotype were also significantly higher in the patient group (P <
      0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-alpha GA were
      significantly decreased in the patients with IBS (P < 0.001). CONCLUSION: IL-6
      and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual
      susceptibility to IBS and might have a role in pathophysiology of disease.

PMID- 19844780
TI  - Effect of exercise on dopamine neuron survival in prenatally stressed rats.
AB  - Prenatal stress has been associated with increased vulnerability to psychiatric
      disturbances including schizophrenia, depression, attention-deficit hyperactivity
      disorder and autism. Elevated maternal circulating stress hormones alter
      development of neural circuits in the fetal brain and cause long-term changes in
      behaviour. The aim of the present study was to investigate whether mild prenatal
      stress increases the vulnerability of dopamine neurons in adulthood. A low dose
      of 6-hydroxydopamine (6-OHDA, 5 microg/4 microl saline) was unilaterally infused
      into the medial forebrain bundle of nerve fibres in the rat brain in order to
      create a partial lesion of dopamine neurons which was sufficient to cause subtle
      behavioural deficits associated with early onset of Parkinson's disease without
      complete destruction of dopamine neurons. Voluntary exercise appeared to have a
      neuroprotective effect resulting in an improvement in motor control and decreased
      asymmetry in the use of left and right forelimbs to explore a novel environment
      as well as decreased asymmetry of tyrosine hydroxylase-positive cells in the
      substantia nigra pars compacta and decreased dopamine cell loss in 6-OHDA
      lesioned rats. Prenatal stress appeared to enhance the toxic effect of 6-OHDA
      possibly by reducing the compensatory adaptations to exercise.

PMID- 19844781
TI  - Exercise increases BDNF levels in the striatum and decreases depressive-like
      behavior in chronically stressed rats.
AB  - Early life stress in humans can affect the development of neurons and
      neurotransmitter systems and predispose an individual to the subsequent
      development of depression. Similarly, in rats, maternal separation causes anxiety
      and depressive-like behavior and decreased corticosterone levels. Patients
      receiving pharmacological treatment for depression often experience negative side
      effects or do not respond optimally and therefore the use of exercise as
      alternative antidepressant treatment is investigated. The aim of the study was to
      see whether rats subjected to both early life stress and chronic stress later in
      life show differences in depressive-like behavior, neurotrophin levels, stress
      hormone levels and antioxidant capacity of serum after chronic voluntary exercise
      as treatment. Rat pups were maternally separated and one group were allowed
      access to running wheels for 6 weeks while control rats were also handled and put
      in cages without running wheels. All rats were subjected to chronic restraint
      stress during adulthood. A forced swim test was done to test for depressive-like
      behavior. Neurotrophins were measured in the ventral hippocampus and striatum;
      baseline stress hormones were measured in blood plasma as well as the anti
      oxidative potential of serum. Compared to controls, rats that exercised had no
      difference in baseline stress hormones, but had decreased immobility times in the
      forced swim test, increased brain derived neurotrophic factor (BDNF) levels in
      the striatum and decreased anti-oxidative potential of their serum. The mechanism
      by which depressive-like behavior was improved may have been mediated through
      increased striatal BDNF levels, resulting in increased neuroplasticity and the
      prevention of neuronal death.

PMID- 19844783
TI  - Reversible vestibular dysfunction secondary to sotalol use.

PMID- 19844782
TI  - Beneficial effects of TLR-2/6 ligation in pulmonary bacterial infection and
      immunization with Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa (P. aeruginosa) is the major pathogen in nosocomial and
      life-threatening infections of immunocompromised or critically ill patients. The
      macrophage-activating lipopeptide-2 (MALP-2) activates the immune system via Toll
      like receptors (TLR) 2 and 6 and leads to an accumulation of immune cells in
      lungs of young adult (8-10 week old) rats after intratracheal application. This
      is characterized by a high increase of granulocyte numbers in the BAL 24 h after
      MALP-2 treatment. It was hypothesized that MALP-2 may have a positive effect on
      the clinical course of an experimental infection. Therefore, rats were treated
      with MALP-2 at different time points following an infection with P. aeruginosa.
      The effect of MALP-2 in combination with immunization with inactivated P.
      aeruginosa was also investigated. Rats (n = 10) were infected intratracheally
      (i.t.) with 1 x 10(8) CFU P. aeruginosa on day 0. They were treated on day -3, 
      1, 0 and +1 with 2.5 microg MALP-2 or the vehicle i.t. In additional experiments,
      rats were immunized on day -21 and -14 with 1 x 10(8) CFU of inactivated P.
      aeruginosa bacteria and 2.5 microg MALP-2 or vehicle with 1 x 10(8) CFU of
      inactivated bacteria and isopropanol. The clinical score, rectal temperature and
      weight of the rats were checked in both treatment and immunization experiments
      twice a day. On day 2 they were sacrificed, CFU were determined in the left lung,
      the right lung being used for histology. In the group treated with MALP-2 1 day
      prior to infection significant effects were seen: The rectal temperature was
      about 2 degrees C higher in comparison to the controls at 6 h and also 1 day
      after infection. Both the symptoms of the infection and the weight loss were
      significantly reduced. In addition, the CFU and the inflammation in the lung
      tissue were significantly lower. These effects were not observed after treatment
      on day -3, 0 or +1. The MALP-2 enhanced immunization only resulted in a tendency
      to clinical improvement. In conclusion, local immunostimulation at the
      appropriate time can enhance the host defense against bacteria in the lung.

PMID- 19844784
TI  - Evaluation of atrial vulnerability immediately after radiofrequency catheter
      ablation of accessory pathway in patients with Wolff-Parkinson-White syndrome.
AB  - PURPOSE: The intrinsic atrial vulnerability is proposed as one of the mechanisms
      of paroxysmal atrial fibrillation (PAF) in Wolff-Parkinson-White (WPW) syndrome.
      In this study, we examined the early changes in atrial refractoriness and intra-
      and inter-atrial conduction times after radiofrequency (RF) catheter ablation of
      accessory pathway (AP). METHODS: Twenty-four consecutive patients with WPW
      syndrome and documented AV reciprocating tachycardia but without history of PAF
      (fourteen male, mean age 39 +/- 9.5 years) and 27 control subjects (six female,
      mean age 51.4 +/- 10.1 years) with AV nodal reentrant tachycardia (AVNRT) who
      underwent ablation of the slow AV nodal pathways were enrolled into the study.
      Regional atrial effective refractory periods (AERPs), AERP dispersion, and intra-
      and inter-atrial conduction times were obtained before and 30 min after ablation
      and were compared between two groups. In the study group, patients with and
      without inducible AF were also compared regarding these parameters. RESULTS: In
      the study group, AERPs in higher right atrium and right posterolateral atrium
      were significantly increased, and AERP dispersion, intra-atrial, and inter-atrial
      conduction times were significantly decreased after ablation; AERP in distal
      coronary sinus was unchanged. In control group, no significant difference was
      observed in these parameters. Inducibility of AF was significantly reduced
      following ablation of AP in the study group (from seven to zero of 24 patients, p
      = 0.016). Comparison between patients with (n = 7) and without (n = 17) AF
      revealed that left atrium diameter was larger, AERPs in the right posterolateral
      atrium before and after ablation, and ERP of AP were shorter in AF group.
      CONCLUSION: In WPW syndrome patients, RF catheter ablation of AP results in an
      'immediate' decrease in atrial vulnerability. Since inducibility of AF becomes
      more difficult in this less vulnerable atrium, the AP itself may play an
      important role in the development of AF.

PMID- 19844785
TI  - A clinical puzzle: fibrates and homocysteine elevation: editorial to: "fibrates
      may cause an abnormal urinary betaine loss which is associated with elevations in
      plasma homocysteine" by M. Lever et al.

PMID- 19844786
TI  - A characterization of the time-rescaled gamma process as a model for spike
      trains.
AB  - The occurrence of neuronal spikes may be characterized by not only the rate but
      also the irregularity of firing. We have recently developed a Bayes method for
      characterizing a sequence of spikes in terms of instantaneous rate and
      irregularity, assuming that interspike intervals (ISIs) are drawn from a
      distribution whose shape may vary in time. Though any parameterized family of ISI
      distribution can be installed in the Bayes method, the ability to detect firing
      characteristics may depend on the choice of a family of distribution. Here, we
      select a set of ISI metrics that may effectively characterize spike patterns and
      determine the distribution that may extract these characteristics. The set of the
      mean ISI and the mean log ISI are uniquely selected based on the statistical
      orthogonality, and accordingly the corresponding distribution is the gamma
      distribution. By applying the Bayes method equipped with the gamma distribution
      to spike sequences derived from different ISI distributions such as the log
      normal and inverse-Gaussian distribution, we confirm that the gamma distribution
      effectively extracts the rate and the shape factor.

PMID- 19844787
TI  - Genomic imprinting disorders in humans: a mini-review.
AB  - Mammals inherit two complete sets of chromosomes, one from the father and one
      from the mother, and most autosomal genes are expressed from both maternal and
      paternal alleles. Imprinted genes show expression from only one member of the
      gene pair (allele) and their expression are determined by the parent during
      production of the gametes. Imprinted genes represent only a small subset of
      mammalian genes that are present but not imprinted in other vertebrates. Genomic
      imprints are erased in both germlines and reset accordingly; thus, reversible
      depending on the parent of origin and leads to differential expression in the
      course of development. Genomic imprinting has been studied in humans since the
      early 1980's and accounts for several human disorders. The first report in humans
      occurred in Prader-Willi syndrome due to a paternal deletion of chromosome 15 or
      uniparental disomy 15 (both chromosome 15s from only one parent) and similar
      genetic disturbances were reported later in Angelman syndrome.

PMID- 19844788
TI  - Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to
      neoadjuvant endocrine therapy for estrogen receptor positive breast cancer.
AB  - Mutations in the alpha catalytic subunit of phosphoinositol-3-kinase (PIK3CA)
      occur in approximately 30% of ER positive breast cancers. We therefore sought to
      determine the impact of PIK3CA mutation on response to neoadjuvant endocrine
      therapy. Exons 9 (helical domain) and 20 (kinase domain-KD) mutations in PIK3CA
      were determined samples from four neoadjuvant endocrine therapy
      trials.Interactions with clinical, pathological, and biomarker response
      parameters were examined. A weak negative interaction between PIK3CA mutation
      status and clinical response to neoadjuvant endocrine treatment was detected(N =
      235 P < or = 0.05), but not with treatment-induced changes in Ki67-based
      proliferation index (N = 418). Despite these findings, PIK3CA KD mutation was a
      favorable prognostic factor for relapse-free survival (RFS log-rank P = 0.02) in
      the P024 trial (N = 153). The favorable prognostic effect was maintained in a
      multivariable analysis(N = 125) that included the preoperative endocrine
      prognostic index, an approach to predicting RFS based on post neoadjuvant
      endocrine therapy pathological stage, ER, and Ki67 levels (HR for no PIK3CA KD
      mutation, 14, CI 1.9-105 P = 0.01). PIK3CA mutation status did not strongly
      interact with neoadjuvant endocrine therapy responsiveness in estrogen receptor
      positive breast cancer. Nonetheless, as with other recent studies, a favorable
      interaction between PIK3CA KD mutation and prognosis was detected. The mechanism
      for the favorable prognostic impact of PIK3CA mutation status therefore remains
      unexplained.

PMID- 19844789
TI  - No direct binding of the heat-labile enterotoxin of Escherichia coli to E. coli
      lipopolysaccharides.
AB  - A novel carbohydrate binding site recognizing blood group A and B determinants in
      a hybrid of cholera toxin and Escherichia coli heat-labile enterotoxin B-subunits
      (termed LCTBK) has previously been described, and also the native heat-labile
      enterotoxin bind to some extent to blood group A/B terminated glycoconjugates.
      The blood group antigen binding site is located at the interface of the B
      subunits. Interestingly, the same area of the B-subunits has been proposed to be
      involved in binding of the heat-labile enterotoxin to lipopolysaccharides on the
      bacterial cell surface. Binding of the toxin to lipopolysaccharides does not
      affect the GM1 binding capacity. The present study aimed at characterizing the
      relationship between the blood group A/B antigen binding site and the
      lipopolysaccharide binding site. However, no binding of the B-subunits to E. coli
      lipopolysaccharides in microtiter wells or on thin-layer chromatograms was
      obtained. Incubation with lipopolysaccharides did not affect the binding of the B
      subunits of heat-labile enterotoxin of human isolates to blood group A-carrying
      glycosphingolipids, indicating that the blood group antigen site is not involved
      in LPS binding. However, the saccharide competition experiments showed that GM1
      binding reduced the affinity for blood group A determinants and vice versa,
      suggesting that a concurrent occupancy of the two binding sites does not occur.
      The latter finding is related to a connection between the blood group antigen
      binding site and the GM1 binding site through residues interacting with both
      ligands.

PMID- 19844790
TI  - Profiles of protection from substance use among adolescents.
AB  - The purpose of this study was to explore whether adolescents (N = 10,287) could
      be classified into homogeneous subgroups based on their protective factors and,
      if so, whether these constellations of protection differentially relate to
      adolescents' lifetime and 30-day alcohol and tobacco use. Latent class analysis
      with eight protective factors--four internal and four external--were used to
      identify the underlying latent class structure. Five profiles of protection
      emerged: Adequate Protection (54%), Adequate External Protection (9%), Adequate
      Protection with Low Adult Communication (16%), Adequate Protection with Risky
      Friends (9%), and Inadequate Protection (12%). Lifetime alcohol use was
      associated with only a modest increase in odds of belonging to the Adequate
      External or Low Adult Communication latent classes, but an enormous increase in
      odds of having Inadequate Protection or Risky Friends. Similar effects were found
      for past month alcohol use. Unlike alcohol use, which was related most strongly
      with membership in the Risky Friends latent class (relative to Adequate
      Protection), cigarette use was most strongly related to membership in the
      Inadequate Protection latent class. Findings can be used to inform prevention
      programs as they illustrate the relationships that exist between adolescents'
      profiles of protection and substance use.

PMID- 19844791
TI  - Preparing to be creative in the NHS: making it personal.
AB  - There is currently a clarion call for the NHS to be more creative and innovative,
      as it moves into an increasingly quality focused agenda. But exactly how easy is
      it to do this when the NHS performance regime for the last 10 years has been more
      about delivering centrally driven, specific and detailed targets for improvement,
      such as reduction of waiting times, than promoting a culture that speaks of
      experimentation and possibilities rather than certainties. Can a workforce that
      may not have been all that prepared for creativity, be creative? And what does
      being prepared for creativity look like? This paper explores, briefly, the
      relationship the NHS has with creativity and the new agendas that are creating
      more fertile ground but then, drawing on practices and information from leading
      innovators and researchers in the business sector, it looks at the conditions the
      NHS might need to create in order foster creativity in its workforce. More
      specifically it looks at the role that a more personal approach to creativity
      might play in cultivating a workforce that is more comfortable entering into
      creative thinking and behaviour.

PMID- 19844792
TI  - Sleep duration and regularity are associated with behavioral problems in 8-year
      old children.
AB  - BACKGROUND: Relatively little is known about the significance of normal variation
      in objectively assessed sleep duration and its regularity in children's
      psychological well-being. PURPOSE: We explored the associations between sleep
      duration and regularity and behavioral and emotional problems in 8-year-old
      children. METHODS: A correlational design was applied among an epidemiological
      sample of children born in 1998. Sleep was registered with an actigraph for seven
      nights (range 3 to 14) in 2006. Mothers (n = 280) and fathers (n = 190) rated
      their child's behavioral problems with the Child Behavior Checklist. RESULTS:
      Children with short sleep duration had an increased risk for behavioral problems,
      thought problems, and Diagnostic and Statistical Manual of Mental Disorders, 4th
      Edition-based attention-deficit hyperactivity problems according to maternal
      ratings. Based on paternal ratings, short sleep duration was associated with more
      rule-breaking and externalizing symptoms. Irregularity in sleep duration from
      weekdays to weekends was associated with an increased risk for specifically
      internalizing symptoms in paternal ratings. CONCLUSIONS: The results highlight
      the importance of sufficient sleep duration and regular sleep patterns from
      weekdays to weekends. Short sleep duration was associated specifically with
      problems related to attentional control and externalizing behaviors, whereas
      irregularity in sleep duration was, in particular, associated with internalizing
      problems.

PMID- 19844793
TI  - Genetic diversity and population structure of Salvia miltiorrhiza Bge in China
      revealed by ISSR and SRAP.
AB  - Salvia miltiorrhiza Bge is a traditional Chinese medicinal herb used as an
      important drug to cure cardiovascular diseases. In this work, inter simple
      sequence repeats (ISSR) and sequence related amplified polymorphism (SRAP)
      markers, were applied to assess the level and pattern of genetic diversity in
      five important cultivated populations of S. miltiorrhiza. Among these
      populations, 120 bands were amplified by 5 ISSR primers, of which all were
      polymorphic, and 110 polymorphic bands (90.16%) were observed in 122 bands
      amplified by 6 SRAP primers. A high levels of genetic diversity at the species
      level was detected with Hs = 0.1951, 0.1927 respectively. Analysis of molecular
      variance revealed that a greater proportion of total genetic variation existed
      within populations (86.64 and 84.83% respectively) rather than among populations
      (13.36 and 15.17% respectively). Cluster analysis divided the five populations
      into two groups. The genetic relationships among populations have low correlation
      with their geographical distribution (Mantel test; r = 0.4870 and 0.5740
      respectively). The study indicated that both ISSR and SRAP markers were effective
      and reliable for assessing the degree of genetic variation of S. miltiorrhiza.
      Our results suggested that random collecting, preserving and planting seeds
      without deliberate selection might be an efficient way to conserve genetic
      resources of medicinal plants. Their effective use was also discussed on the
      further breeding.

PMID- 19844794
TI  - Can statin therapy reduce the risk of melanoma? A meta-analysis of randomized
      controlled trials.
AB  - A growing body of literature suggests that statins may have a chemopreventive
      potential against melanoma through pleiotropic anti-inflammatory,
      immunomodulatory, and antiangiogenesis mechanisms. Our aim was to examine this
      association through a detailed meta-analysis of randomized controlled trials
      (RCTs). A comprehensive search for trials published up to June 2009 was
      performed, reviews of each study were conducted and data were abstracted. Prior
      to meta-analysis, the studies were evaluated for publication bias and
      heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals
      (CIs) were calculated using the fixed- and the random-effects models. Subgroup
      and sensitivity analyses were also conducted. Sixteen RCTs of statins for
      cardiovascular outcomes, involving 62,568 individuals with a mean age of 60 years
      and an average follow-up of nearly 4.7 years, contributed to the analysis. We
      found no evidence of publication bias (P = 0.47) or heterogeneity among the
      studies (P = 0.25). Statin use did not significantly affect the risk of
      developing melanoma assuming either a fixed- (RR = 0.92, 95% CI: 0.67-1.26), or a
      random-effects model (RR = 0.92, 95% CI: 0.62-1.36). This neutral effect was
      further supported by the results of subgroup and sensitivity analyses. Our
      findings do not support a protective effect of statins against melanoma.

PMID- 19844795
TI  - Adventive eriophyoid mites: a global review of their impact, pathways, prevention
      and challenges.
AB  - Eriophyoids have high potential as adventive mite species (AMS) because their
      small size make them difficult to detect, and can be easily distributed in world
      trade. Economic, social and environmental impact from adventive eriophyoid mites
      has been significant. Considerable attention has been given to adventive insect
      species while adventive mites have received little attention and little
      information is available for eriophyoids. This paper summarizes information on
      adventive eriophyoid mites, their impact, and the history of some important
      invasions. The status of adventive species of eriophyoids introduced as
      biological control agents of weeds is presented. A list of eriophyoid mites
      reported as invasive species worldwide is given. Pathways of concern and
      biosecurity actions to reduce the risk of eriophyoid mites are discussed. The
      need to raise public awareness of the risk and importance of these tiny organisms
      as AMS is emphasized. Scientific and technical challenges to deal with adventive
      eriophyoids are discussed.

PMID- 19844796
TI  - Transjugular intrahepatic portosystemic shunt (TIPS): the anesthesiological point
      of view after 150 procedures managed under total intravenous anesthesia.
AB  - TIPS is a percutaneous procedure which diverts blood from the portal to the
      systemic circulation preventing rebleeding from varices and stopping or reducing
      the formation of ascites. The choice of the anaesthetic technique is still a
      matter of debate. Since January 2003, 150 consecutive TIPS were performed using
      total intravenous anesthesia (TIVA), (propofol/fentanyl or remifentanil),
      endotracheal intubation and mechanical ventilation. Sixty-one patients were
      classified as ASA 2, 73 ASA 3, and 16 ASA 4. According to CHILD classification,
      96 patients were in Class A, 48 in Class B, 6 in Class C. Mean duration f the
      procedure was 100+/-62 min. After TIPS placement Portal vein pressure decreased
      from 30+/-10 to 14+/-4 mmHg while RAP increased from 8+/-4 to 12+/-6 mmHg.
      Intraoperative fluid management included mainly crystalloids (750+/-200 ml, 5.4+/
      1.5 ml/kg/h). Fresh frozen plasma (median 2 units, range 1-3) was given in 20
      patients (13%) if PT INR was >2. Packed red cells (median 2 units, range 1-5)
      were transfused in 35 patients (23%) to keep haematocrit >25%; platelets were
      administered before the procedure if platelet count was <50,000x10(-9) (20
      patients, 13%). Urine output was kept above 4 ml/kg/h with loops diuretics (mean
      diuresis 700+/-200 ml, 5+/-1.5 ml/kg/h). Ten patients (6.6%) required ICU after
      the procedure, because of intraoperative hemodynamic instability. Three patients
      (2%) died in the early postoperative period because of multiple organ failure
      associated with the acute deterioration of an already marginal hepatic function.

PMID- 19844797
TI  - Plasma enterolactone and risk of colon and rectal cancer in a case-cohort study
      of Danish men and women.
AB  - This case-cohort study examined the association between plasma enterolactone
      concentration and incidence of colon and rectal cancer in the Diet, Cancer and
      Health cohort, which enrolled 57,053 participants aged 50-64. Information about
      diet and lifestyle was obtained by questionnaire, and data on prescriptions of
      antibiotics were obtained from the Danish Prescription Registry. Cases diagnosed
      during 5.9 years of follow-up and a randomly selected sample of the cohort had a
      plasma sample analyzed for enterolactone by time-resolved fluoro-immuno assay.
      Associations were analyzed by Cox proportional hazards model. A total of 244
      colon cancer cases, 137 rectal cancer cases, and 370 sub-cohort members were
      included in the statistical analyses. For each doubling in enterolactone
      concentration, we found lower risk of colon cancer among women [IRR (95% CI) =
      0.76 (0.60-0.96)] and a tendency toward lower risk of rectal cancer [IRR (95% CI)
      = 0.83 (0.60-1.14)]. Among men, a doubling in enterolactone tended to be
      associated with higher risk of colon cancer [IRR (95% CI) = 1.09 (0.89-1.34)] and
      was associated with statistically significantly higher risk of rectal cancer [IRR
      (95% CI) = 1.74 (1.25-2.44)]. Exclusion of antibiotics users strengthened the
      results slightly. In conclusion, with higher enterolactone levels, we found lower
      risk of colon cancer among women and higher risk of rectal cancer among men.

PMID- 19844798
TI  - Screening mammography intervals among postmenopausal hormone therapy users and
      nonusers.
AB  - BACKGROUND: The recent decline in US breast cancer incidence rates has been
      attributed to the marked reduction in use of postmenopausal hormone therapy (HT).
      An alternative explanation is that women who are not routinely seeking medical
      care to renew HT prescriptions may be less adherent to recommendations for
      mammographic screening. To investigate the latter possibility, we compared
      mammographic intervals according to HT use. METHODS: Using data (1995-2007) from
      the New Hampshire Mammography Network (NHMN), a state-based mammography registry,
      we assessed mammographic intervals corresponding to HT use or nonuse among
      postmenopausal women. We used linear mixed effects models to assess whether the
      length of screening mammogram intervals differed according to HT use. RESULTS: A
      total of 310,185 mammograms, representing 76,192 postmenopausal women and 319,353
      person-years of screening, were included in the analysis. The median screening
      interval corresponding to HT use overall was 13.0 months (interquartile range:
      12.4-15.1) and for nonuse was 13.1 (interquartile range: 12.4-15.8). Virtually,
      all screening mammograms occurred within a 2-year interval regardless of HT use
      or nonuse (98.5 and 98.1%, respectively). CONCLUSIONS: Our findings indicate that
      screening mammography intervals are similar whether or not women are using HT.
      Thus, reduced utilization of screening mammography is unlikely to account for the
      decrease in breast cancer incidence seen soon after the WHI report.

PMID- 19844799
TI  - Higher axial-resolution and sensitivity pachytene fluorescence in situ
      hybridization protocol in tetraploid cotton.
AB  - Fluorescence in situ hybridization (FISH) based on pachytene chromosomes has
      become an important cytogenetic tool to construct high axial-resolution and
      sensitivity cytogenetic maps. However, the application of this technique in
      cotton has lagged behind due to difficulties in chromosome preparation. To date,
      successful FISH based on cotton pachytene chromosomes has not been reported. In
      this study, the first protocol developed for pachytene chromosome preparation in
      tetraploid cotton is presented. This protocol yielded chromosome spreads suitable
      for large and small DNA probe FISH labeling. Two important parameters, axial
      resolution and sensitivity, of FISH on mitotic metaphase and pachytene
      chromosomes were systematically analyzed. The results demonstrated that DNA
      targets separated by 0.6 cM and low-copy targets as small as 3-kb were resolved
      and detected, respectively, in pachytene FISH. The application of our FISH
      protocol will continue to improve and provide a point of departure for
      constructing an integrated high axial-resolution cytogenetic map in cotton.

PMID- 19844800
TI  - Stochastic approaches for time series forecasting of boron: a case study of
      Western Turkey.
AB  - In the present study, a seasonal and non-seasonal prediction of boron
      concentrations time series data for the period of 1996-2004 from Buyuk Menderes
      river in western Turkey are addressed by means of linear stochastic models. The
      methodology presented here is to develop adequate linear stochastic models known
      as autoregressive integrated moving average (ARIMA) and multiplicative seasonal
      autoregressive integrated moving average (SARIMA) to predict boron content in the
      Buyuk Menderes catchment. Initially, the Box-Whisker plots and Kendall's tau test
      are used to identify the trends during the study period. The measurements
      locations do not show significant overall trend in boron concentrations, though
      marginal increasing and decreasing trends are observed for certain periods at
      some locations. ARIMA modeling approach involves the following three steps: model
      identification, parameter estimation, and diagnostic checking. In the model
      identification step, considering the autocorrelation function (ACF) and partial
      autocorrelation function (PACF) results of boron data series, different ARIMA
      models are identified. The model gives the minimum Akaike information criterion
      (AIC) is selected as the best-fit model. The parameter estimation step indicates
      that the estimated model parameters are significantly different from zero. The
      diagnostic check step is applied to the residuals of the selected ARIMA models
      and the results indicate that the residuals are independent, normally
      distributed, and homoscadastic. For the model validation purposes, the predicted
      results using the best ARIMA models are compared to the observed data. The
      predicted data show reasonably good agreement with the actual data. The
      comparison of the mean and variance of 3-year (2002-2004) observed data vs
      predicted data from the selected best models show that the boron model from ARIMA
      modeling approaches could be used in a safe manner since the predicted values
      from these models preserve the basic statistics of observed data in terms of
      mean. The ARIMA modeling approach is recommended for predicting boron
      concentration series of a river.

PMID- 19844801
TI  - Ecotoxicity assessment of aged petroleum sludge using a suite of effects-based
      end points in earthworm Eisenia fetida.
AB  - Laboratory investigations were conducted to test the toxicity of aged petroleum
      sludge collected from Shengli Oil Field, the second largest oilfield in China, to
      earthworm Eisenia fetida. Various end points were measured in the earthworms,
      including mortality, growth, cocoon output, juvenile production, and avoidance
      behavioral response, to determine their comparative sensitivity for assessing
      harmful effects of petroleum-hydrocarbon-contaminated soil. The results showed
      that all these assays responded in a concentration-dependent manner, and two
      chronic end points, juvenile production and cocoon output, as well as avoidance
      behavioral response appeared to be sensitive end points for detecting toxicity of
      petroleum-hydrocarbon-contaminated soil. Comparatively, juvenile production
      exhibited similar sensitivity to avoidance behavior response, both of which were
      more sensitive than cocoon output, while mortality and adult growth were proposed
      as the least sensitive parameters. It was suggested that large amounts of
      petroleum sludge deposited in Shengli Oil Field may pose a potential threat to
      the local ecosystem, and the utility of multiple effects-based end points in
      earthworm E. fetida is useful to facilitate ecological risk assessments in
      hydrocarbon-contaminated sites.

PMID- 19844802
TI  - Responses of Atlantic cod Gadus morhua head kidney leukocytes to phytase produced
      by gastrointestinal-derived bacteria.
AB  - This study identified phytase-producing bacteria that were previously isolated
      from the gastrointestinal tract of Atlantic cod, Gadus morhua and determined its
      effect on head kidney leukocytes. Out of the 216 bacterial strains tested, the
      two phytase producers were identified as Pseudomonas sp. and Psychrobacter sp.
      based on their 16S rDNA sequence. Crude phytase from these two bacterial strains
      was produced employing the shake flask method. Even though the total protein of
      the crude phytase was not significantly different for the two bacteria, the
      phytase activity of the crude enzyme produced by Pseudomonas sp. (97.1+/-16.7 U)
      was significantly higher than that of the enzyme from Psychrobacter sp. (75.9+/
      2.4 U). When cod head kidney leukocytes were incubated with the crude phytase (50
      MUg ml(-1)), it resulted in enhanced cell proliferation, higher myeloperoxidase,
      and acid phosphatase activities. Extracellular responses-respiratory burst
      activity and hydrogen peroxide production were not enhanced by the crude enzyme.
      As a consequence, the growth of two pathogenic bacteria Aeromonas salmonicida and
      Vibrio anguillarum was not suppressed by the supernatants obtained from head
      kidney leukocytes incubated with the crude bacterial phytase. Thus, the enzyme
      from phytase-producing intestinal bacteria of Atlantic cod can stimulate
      intracellular head kidney leukocyte activities but not the production of
      extracellular substances that are involved in antibacterial response. These have
      implications on the potential use of bacterial phytase as feed supplement to
      boost cellular immune response of the fish and could be employed as a health
      management strategy in culture systems.

PMID- 19844803
TI  - Fertility comparison between wild type and transgenic mice by in vitro
      fertilization.
AB  - Transgenic mice are increasingly used as animal models for studies of gene
      function and regulation of mammalian genes. Although there has been continuous
      and remarkable progress in the development of transgenic technology over several
      decades, many aspects of the resulting transgenic model's phenotype cannot be
      completely predicted. For example, it is well known that as a consequence of the
      random insertion of the injected DNA construct, several founder mice of the new
      line need to be analyzed for possible differences in phenotype secondary to
      different insertion sites. The Knock out technique for transgenic production
      disrupts a specific gene by insertion or homologous recombination creating a null
      expression or replacement of the gene with a marker to localize it expression.
      This modification could result in pleiotropic phenotype if the gene is also
      expressed in tissues other than the target organs. Although the future breeding
      performance of the newly created model is critical to many studies, it is rarely
      anticipated that the new integrations could modify the reproductive profile of
      the new transgenic line. To date, few studies have demonstrated the difference
      between the parent strain's reproductive performance and the newly developed
      transgenic model. This study was designed to determine whether a genetic
      modification, knock out (KO) or transgenics, not anticipated to affect
      reproductive performance could affect the resulting reproductive profile of the
      newly developed transgenic mouse. More specifically, this study is designed to
      study the impact of the genetic modification on the ability of gametes to be
      fertilized in vitro. We analyzed the reproductive performance of mice with
      different background strains: FVB/N, C57BL/6 (129Sv/J x C57Bl/6)F1 and outbred
      CD1((R)) and compared them to mice of the same strain carrying a transgene or KO
      which was not anticipated to affect fertility. In vitro Fertilization was used to
      analyze the fertility of the mice. Oocytes from superovulated females were
      inseminated with sperm of same background. Fertility rate was considered as the
      percentage of two cell embryos scored 24 h after insemination. The data collected
      from this study shows that the fertilization rate is affected (reduced to half
      fold) in some of the transgenic mice compared to the respective Wild Type (WT)
      mice. For the WT the average fertility rate ranged from 80% (C57BL/6), 90%
      (FVB/N), 45% (129Sv/J x C57Bl/6)F1 and 43% (CD1). For transgenic mice it was 52%
      (C57BL/6), 65% (FVB/N), 22% (129Sv/J x C57Bl/6)F1 and 25% (CD1).

PMID- 19844804
TI  - Vitamin D and ageing.
AB  - Within the past three to four decades a revolution has occurred in our
      understanding of vitamin D and its effects. Sundry laboratory and epidemiologic
      studies have revealed that the active metabolite of vitamin D controls and/or
      ameliorates various pathologies. As presented here, there is substantive evidence
      that vitamin D may play a positive and important role in the ageing process.This
      evidence arises from detailed consideration of various biological mechanisms and
      processes by which vitamin D operates as well as specific examples of its
      exerting control/amelioration of various human maladies which contribute to
      ageing. Arguments are advanced that vitamin D appears to play a major positive
      role in biogerontology by reducing susceptibility in the elderly to chronic
      degenerative diseases. It is strongly recommended that the positive role of
      vitamin D in ageing be taken into account by gerontologists and biogerontology
      researchers.

PMID- 19844805
TI  - Risk and distributive justice: the case of regulating new technologies.
AB  - There are certain kinds of risk for which governments, rather than individual
      actors, are increasingly held responsible. This article discusses how regulatory
      institutions can ensure an equitable distribution of risk between various groups
      such as rich and poor, and present and future generations. It focuses on cases of
      risk associated with technological and biotechnological innovation. After
      discussing various possibilities and difficulties of distribution, this article
      proposes a non-welfarist understanding of risk as a burden of cooperation.

PMID- 19844806
TI  - The role of thrombospondins in wound healing, ischemia, and the foreign body
      reaction.
AB  - Thrombospondin (TSP) 1 and TSP2 have been implicated in the regulation of several
      processes during tissue repair. Due to their matricellular nature, these proteins
      are thought to modulate cell-matrix interactions through a variety of mechanisms
      specific to the spatio-temporal context of their expression. Most notably, TSP1
      and TSP2 appear to play distinct, non-overlapping roles in the healing of skin
      wounds. In contrast, both proteins have been implicated as regulators of ischemia
      induced angiogenesis. Moreover, TSP2 has been shown to be a critical regulator of
      angiogenesis in the foreign body response (FBR). In this review, we discuss the
      role of TSPs in tissue repair and examine the mechanistic data regarding the
      ability of the thrombospondins to modulate cell-matrix interactions in this
      context.

PMID- 19844807
TI  - NMR assignment of actin depolymerizing and dynamics  regulatory protein from
      Leishmania donovani.
AB  - Leishmania donovani cofilin displays low sequence similarity to other mammalian
      cofilins and also possesses characteristic activity of its own. Determination of
      its solution structure would facilitate understanding of the molecular mechanism
      of actin dynamics regulation in this disease causing pathogen.

PMID- 19844809
TI  - How I manage the adult potential organ donor: donation after neurological death
      (part 1).
AB  - The need for organ donation has become a growing concern over that last decade as
      the gap between organ donors and those awaiting transplant widens. According to
      UNOS, as of 8/2009, there were 102,962 patients on the transplant waiting list
      and only 6,004 donors in 2009 (UNOS.org. Accessed 4/8/2009). In 2008, an
      estimated 17 patients died each day awaiting transplant (OPTN.org). Though
      currently most organ donations come after brain death (DND or donation after
      neurological death), tissue donation (cornea, skin, bone, and musculoskeletal
      tissue), and donation after cardiac death (DCD) and are also possible. The term
      "extended criteria donor" refers to potential donors over 60 years of age or age
      50-59 years plus 2 of the 3 following criteria: stroke as the cause of death,
      creatnine > 1.5 meq/dl, or a history of hypertension. Historically, extended
      criteria donors have had a lower organ yield per donor. In order to preserve the
      choice of organ donation for the family, intensive management of the potential
      organ donor is necessary. Since each potential donor could save seven lives or
      more, nihilism in the care of such patients can have far reaching ramifications.
      This article describes intensive care management practices that can optimize
      organ donation.

PMID- 19844808
TI  - Activity-dependent neuroprotective protein (ADNP) expression in the amyloid
      precursor protein/presenilin 1 mouse model of Alzheimer's disease.
AB  - A major determinant in the pathogenesis of Alzheimer's disease (AD) is the
      deposition of beta-amyloid (Abeta) peptides in specific areas of the central
      nervous system. Therefore, animal models of Alzheimer amyloidosis are excellent
      tools to identify candidates to facilitate drug screening and to understand the
      molecular pathology of AD. Activity-dependent neuroprotective protein (ADNP)
      plays an essential role in brain development, and NAP (NAPVSIPQ, generic name:
      davunetide)--a peptide derived from ADNP--is currently in clinical development
      for the treatment of neurodegenerative disorders. However, the link between ADNP
      expression and AD remains unexplored. To test whether ADNP is affected by the
      onset of AD and progression, we employed the PS1xAPP mouse model (PS1(M146L) x
      APP(751SL) transgenic mice) to analyze the mRNA expression of ADNP in the
      hippocampus and cerebellum in early and advanced stages of disease. Results
      showed that ADNP expression in 6-month-old PS1xAPP mice hippocampus was higher
      than in wild-type (WT) mice. ADNP was originally identified as a vasoactive
      intestinal peptide (VIP)-responsive gene taking part in the VIP-mediated
      neurotrophic pathway. Interestingly, the expression of VIP was not affected in
      the same experimental setting, suggesting that ADNP expression is a VIP
      independent marker associated with AD. Moreover, in the cerebellum, a brain area
      not affected by Abeta deposition, ADNP mRNA expression in 6-month-old PS1xAPP and
      WT were not different. A similar extent of hippocampal ADNP expression was
      observed in 18-month-old WT and PS1xAPP mice, in contrast to the differential
      expression level at 6 months of age. However, hippocampal ADNP expression in both
      WT and PS1xAPP was increased with aging similar to VIP mRNA expression. Our
      findings support the hypothesis that ADNP expression is related to early or mild
      AD progression by a VIP-independent mechanism.

PMID- 19844810
TI  - Role of antiplatelet agents in hematoma expansion during the acute period of
      intracerebral hemorrhage.
AB  - BACKGROUND: Oral anticoagulants have been associated with greater hematoma
      expansion in patients with intracerebral hemorrhage (ICH). The purpose of this
      study was to determine whether the reported use of antiplatelet agents also
      results in greater hematoma expansion. METHODS: Retrospective review of patients
      with spontaneous supratentorial ICH diagnosed within 6 h of onset, who underwent
      follow-up head CT approximately 48 h later. Digital imaging analysis of initial
      and second CT scans was performed for comparison of hematoma volume changes
      between patients reporting and those not reporting antecedent antiplatelet use.
      Statistical analyses to determine predictors of ICH volume change and in-hospital
      mortality were also performed via multivariate regression models. RESULTS: Of the
      70 patients included, 17 were documented as taking antiplatelet agents. Groups
      were comparable regarding baseline demographic, clinical and laboratory
      characteristics, and the timing of CT scans was similar. Patients reporting
      antiplatelet use experienced greater absolute increase (7.7 ml vs. 5.5 ml) and
      proportional increase (110% vs. 21%) in ICH volume than those not reporting
      antiplatelet use, but these differences were not statistically significant (P =
      0.94 and 0.61 respectively; Wilcoxon test). Baseline hematoma volume tended to
      correlate with percentage volume increase (P < 0.1), whereas IVH was inversely
      associated with percent volume increase (P < 0.05). Age (P < 0.05), absolute
      volume increase (P < 0.005), and final volume (P < 0.001) were associated with in
      hospital mortality, the rates of which were similar between the two study groups
      (18% vs. 17%). CONCLUSIONS: Patients reporting antiplatelet use experienced
      similar degrees of hematoma expansion compared to patients not reporting
      antiplatelet use.

PMID- 19844811
TI  - Does the immune system induce labor? Lessons from preterm deliveries in women
      with autoimmune diseases.
AB  - A recent review of the literature suggested that thyroid autoimmunity is
      statistically associated with preterm delivery. This observation raises a number
      of follow-up questions, among them whether autoimmune function, in general,
      predisposes to premature delivery. A review of the English literature for the
      last 10 years, via PubMed search, finds strong supportive evidence for such a
      hypothesis. Since the fetal-placental unit represents a (semi) allograft within a
      maternal (allograft) recipient, it is reasonable to assume that it is subject to
      similar immunologic tolerance (and failure thereof) as solid organ transplants.
      As autoimmune responses represent a normal feature of tolerance failure in organ
      transplantation, similar autoimmune responses can also be expected with failure
      of tolerance of the fetal-maternal graft. The association of premature (and
      possibly also term) labor with autoimmune function may, therefore, be the
      consequence of abnormalities in normal fetal-placental tolerance, leading to
      uterine activation and labor.

PMID- 19844812
TI  - Involvement of Fc receptors in disorders of the central nervous system.
AB  - Immunoglobulins are proteins with a highly variable antigen-binding domain and a
      constant region (Fc domain) that binds to a cell surface receptor (FcR).
      Activation of FcRs in immune cells (lymphocytes, macrophages, and mast cells)
      triggers effector responses including cytokine production, phagocytosis, and
      degranulation. In addition to their roles in normal responses to infection or
      tissue injury, and in immune-related diseases, FcRs are increasingly recognized
      for their involvement in neurological disorders. One or more FcRs are expressed
      in microglia, astrocytes, oligodendrocytes, and neurons. Aberrant activation of
      FcRs in such neural cells may contribute to the pathogenesis of major
      neurodegenerative conditions including Alzheimer's disease, Parkinson's disease,
      ischemic stroke, and multiple sclerosis. On the other hand, FcRs may play
      beneficial roles in counteracting pathological processes; for e.g., FcRs may
      facilitate removal of amyloid peptides from the brain and so protect against
      Alzheimer's disease. Knowledge of the functions of FcRs in the nervous system in
      health and disease is leading to novel preventative and therapeutic strategies
      for stroke, Alzheimer's disease, and other neurological disorders.

PMID- 19844815
TI  - Tamoxifen and arrhythmia.
AB  - Tamoxifen is an orally active selective estrogen receptor modulator that is used
      in the treatment of breast cancer and is currently the world's largest selling
      drug for that purpose. However, it has some side effects including hot flashes,
      menstrual irregularity, vaginal discharges, uterine bleeding, uterine endometrial
      cancer, hypercoagulability, steatosis hepatis, risk of trombembolism. Long-term
      data from clinical trials have failed to demonstrate a cardioprotective effect
      and beneficial effects on serum lipid profiles. Arrhythmia secondary to tamoxifen
      is very rare.

PMID- 19844813
TI  - Determining the neurotransmitter concentration profile at active synapses.
AB  - Establishing the temporal and concentration profiles of neurotransmitters during
      synaptic release is an essential step towards understanding the basic properties
      of inter-neuronal communication in the central nervous system. A variety of
      ingenious attempts has been made to gain insights into this process, but the
      general inaccessibility of central synapses, intrinsic limitations of the
      techniques used, and natural variety of different synaptic environments have
      hindered a comprehensive description of this fundamental phenomenon. Here, we
      describe a number of experimental and theoretical findings that has been
      instrumental for advancing our knowledge of various features of neurotransmitter
      release, as well as newly developed tools that could overcome some limits of
      traditional pharmacological approaches and bring new impetus to the description
      of the complex mechanisms of synaptic transmission.

PMID- 19844814
TI  - FABP4: a novel candidate gene for polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder
      involving a number of genetic and environmental factors. Adipocyte-fatty acid
      binding protein (FABP4) is an adipokine regulating systemic insulin sensitivity,
      lipid and glucose metabolism. In humans serum FABP4 levels correlate
      significantly with features of PCOS. Previous researches showed strong evidences
      that FABP4 impacted the developing of PCOS possibly through its protein
      alteration or transcription regulation. Thus, the present study is the first
      attempt to identify the possible genetic role of FABP4 gene in the development of
      PCOS. METHODS: About 1000 bp of the promoter region and four exons of FABP4 gene
      of 178 PCOS patients and 171 healthy controls were directly sequenced. RESULTS:
      Three polymorphisms, rs16909225, rs3834363, and rs16909220, were identified, of
      which rs16909225 and rs16909220 were completely linked (r2 = 1) and not
      associated with the development of PCOS, while the -2-bp/-2-bp genotype of
      rs3834363 was significantly higher in PCOS than in the controls (chi2 = 7.39, df
      = 1, P = 0.007, OR = 1.80 95% CI: 1.18-2.75). CONCLUSION: The present study is
      the first to establish an association between FABP4 gene polymorphisms and the
      development of PCOS.

PMID- 19844816
TI  - Three-dimensional reconstruction and characterization of human external shapes
      from two-dimensional images using volumetric methods.
AB  - This work presents a volumetric approach to reconstruct and characterise 3D
      models of external anatomical structures from 2D images. Volumetric methods
      represent the final volume using a finite set of 3D geometric primitives, usually
      designed as voxels. Thus, from an image sequence acquired around the object to
      reconstruct, the images are calibrated and the 3D models of the referred object
      are built using different approaches of volumetric methods. The final goal is to
      analyse the accuracy of the obtained models when modifying some of the parameters
      of the considered volumetric methods, such as the type of voxel projection
      (rectangular or accurate), the way the consistency of the voxels is tested (only
      silhouettes or silhouettes and photo-consistency) and the initial size of the
      reconstructed volume.

PMID- 19844817
TI  - CAD/CAM bilateral ear prostheses construction for Treacher Collins syndrome
      patients using laser scanning and rapid prototyping.
AB  - Ear defects in patients affected by Treacher Collins syndrome necessitate the
      replacement of the existing anatomic residuals of the ears with custom-made
      prostheses. This paper describes a multidisciplinary protocol involving both
      medicine and computer-aided design/computer-aided manufacturing for manufacturing
      ear prostheses. Using innovative prototyping technologies together with
      conventional silicone processing procedures, a step-by-step procedure is
      presented. The complete workflow includes laser scanning of the defective regions
      of a patient's face, the use of 3D anatomic models from an ear digital library
      and rapid prototyping of both substructures for bar anchoring and moulds for
      silicone processing.

PMID- 19844818
TI  - Ugandan HIV/AIDS orphans in charge of their households speak out: a study of
      their health-related worries.
AB  - The number of children orphaned due to HIV/AIDS in sub-Saharan Africa was
      estimated in 2007 by UNAIDS at upwards of 12 million. In Uganda alone, 800,000 of
      the estimated 1.6 million orphans are said to be orphaned due to this cause.
      These children suffer life-long consequences from the loss of their parents. This
      study explores the situation of children living in child-headed households in
      Uganda's western Kabarole district. Through qualitative research, including in
      depth interviews with 20 child heads of households, the health concerns of these
      children are documented. The interview data were analysed using qualitative
      research techniques. The study reveals that the psychological and physical
      effects of orphanhood are magnified for those living in child-headed households.
      In particular, it highlights the fears of theft and abuse which are a constant
      source of anxiety for these children. It reports that illness episodes among
      younger siblings are also particularly worrisome for child heads of households.
      The article concludes with recommendations for addressing this urgent problem in
      sub-Saharan Africa.

PMID- 19844820
TI  - Saoussanabiloide, a novel antifungal alkaloid from Echiochilon fruticosum Desf.
      growing in Tunisia.
AB  - Bioactivity guided fractionation of Echiochilon fruticosum Desf. (Boraginaceae)
      butanolic extract biautography assay against fungi led to the isolation of a new
      bioactive alkaloid, named saoussanabiloide (1). Its structure was established on
      the basis of spectroscopic measurements, IR, MS and 2D NMR using COSY, HMQC and
      HMBC experiments. The strongest inhibitory effect of the butanolic extract, from
      fractions derived from the crude extract and saoussanabiloide (1), were observed
      against Fusarium oxysporum f. sp. niveum.

PMID- 19844819
TI  - HIV-associated deficits in action (verb) generation may reflect astrocytosis.
AB  - Commensurate with the hypothesized neural dissociation between verb and noun
      generation, research in HIV infection shows that, relative to noun fluency,
      action (verb) fluency is disproportionately impaired, more strongly related to
      executive dysfunction, and more sensitive to declines in everyday functioning.
      However, whether the neurobiological correlates of HIV-associated deficits in
      verb and noun generation are separable have not heretofore been investigated. The
      present study examined the biomarker correlates of action and noun fluency in 74
      participants with HIV infection. Biomarkers of viral burden, neuroaxonal damage,
      macrophage activation, neuroprotection, inflammation, and astrocytosis were
      measured in plasma and cerebrospinal fluid (CSF). Deficits in action, but not
      noun generation, were significantly associated with higher CSF levels of
      S100beta, a marker of astrocyte activation, even after controlling for
      antiretroviral therapy, current immune compromise, and general cognitive
      impairment. Concurrent validity for the frontal systems hypothesis of verb
      generation was provided by post hoc analyses demonstrating that S100beta was also
      associated with measures of executive functions, but not semantic memory or
      psychomotor speed. Overall, these findings suggest that HIV-associated impairment
      in action fluency, and executive dysfunction more generally, may reflect
      astrocytosis (i.e., elevated S100beta). Complementing the literature in HIV and
      other clinical populations with frontal systems involvement, these data also
      support the possible neurobiological dissociation of noun and verb generation.

PMID- 19844821
TI  - A new antioxidant flavonoid from the lianas of Gnetum macrostachyum.
AB  - A new flavonoid, named 5,7,2'-trihydroxy-5'-methoxyflavone (1), was isolated from
      the acetone extract of the lianas of Gnetum macrostachyum together with 5,7,4'
      trihydroxy-3'-methoxyflavanone (2) and seven known stilbenoids (3-7). The
      structure of the new compound was determined by interpretation of its spectral
      data and chemical transformation. The isolated compounds showed radical
      scavenging activity against DPPH with IC(50) values in the range of 0.21-19.90
      mM.

PMID- 19844822
TI  - Composition and anti-fungal activity of the essential oil from Cameroonian Vitex
      rivularis Gurke.
AB  - The chemical composition of the essential oils obtained by hydrodistillation from
      the aerial parts of two populations of Vitex rivularis (subgenus Vitex) collected
      during the flowering phase of the plants was investigated by gas chromatography
      and gas chromatography/mass spectroscopy. Sesquiterpene hydrocarbons were the
      main group in both samples, the main compound being germacrene D. This
      composition is markedly different from that of the other African species, with
      the exception of Vitex ferruginea subsp. amboniensis, which belongs to the same
      subgenus as V. rivularis. Minimal inhibitory concentrations (MIC) and minimal
      lethal concentrations (MLC) were used to evaluate the anti-fungal activity
      against yeasts and dermatophyte strains. The oils exhibited significant anti
      fungal activity against dermatophyte strains with MIC and MLC values ranging from
      0.16 to 0.64 microL mL(-1) and 0.32 to 2.5 microL mL(-1), respectively. For some
      strains, MIC values were similar to MLC values, indicating the fungicidal
      activity of the oils. Nevertheless, these oils showed low activity against
      Candida spp. strains.

PMID- 19844823
TI  - Synthesis and biological evaluation of pyridinebetaine A and B.
AB  - The synthesis of the marine natural products pyridinebetaine A and B is reported.
      The biological evaluation of pyridinebetaine A and B and several analogues as
      cytotoxic, antifungal and antiviral agents is also described. Unfortunately, none
      of the compounds tested showed relevant antifungal or cytotoxic activity. Only
      pyridinebetaine B reduced the Herpes simplex virus type 1 virus replication,
      though only weakly.

PMID- 19844825
TI  - Antioxidant activity of inflorescences, leaves and fruits of three Sorbus species
      in relation to their polyphenolic composition.
AB  - The antioxidant potential of 70% methanolic extracts from the inflorescences,
      leaves and fruits of Sorbus aucuparia, S. aria and S. intermedia was evaluated
      using three in vitro test systems (DPPH: 2,2-diphenyl-1-picryl hydrazyl; TEAC:
      trolox equivalent antioxidant capacity and FRAP: ferric reducing/antioxidant
      power). High activities found were expressed as micromoles trolox equivalents per
      gram dry weight and were in the range of 86.9-956.2 for the DPPH test, 65.3-577.2
      for the TEAC assay and 221.1-1915.2 for the FRAP method. Significant linear
      correlations (R(2) in the range of 0.75-0.98) between these values and the
      contents of total phenolics, total flavonoids, total proanthocyanidins and
      chlorogenic acid isomers showed that the listed phenolic compounds are
      determinants of the antioxidant capacity tested. As the superior activity and the
      highest phenolic levels (11.83% of total phenolics calculated as gallic acid
      equivalents, 4.35% of chlorogenic acid isomers, 5.01% of proanthocyanidins and
      1.28% of flavonoid aglycones) were found for S. aucuparia inflorescence, this
      plant material has the greatest potential as a source for natural health
      products.

PMID- 19844824
TI  - Cytotoxic and anticarcinogenic activity of the ent-kaurene diterpenoid,
      melissoidesin, from Isodon wightii (Bentham) H. Hara.
AB  - Isodon wightii is a common plant found in the Western Ghats of South India. The
      ent-kaurene diterpenoid melissoidesin, isolated from the leaves of I. wightii,
      showed significant cytotoxicity against lung cancer and neuroblastoma cell lines
      with IC(50) values of 6 and 4.2 microg mL(-1), respectively. The prevention of
      deoxyribose degradation activity of melissoidesin was significant and the IC(50)
      value was calculated to be 163.1 microg mL(-1). The anticarcinogenic activity of
      melissoidesin by comet assay showed significant DNA damage protecting activity in
      a dose-dependent manner.

PMID- 19844826
TI  - A furanocoumarin from Prangos uloptera roots, biological effects.
AB  - A known furanocoumarin, 8-geranyloxy psoralen, was isolated from n-hexane extract
      of Prangos uloptera roots by the TLC method. Its structure was determined by
      comparison of the spectral data with the literature. Cytotoxic effects of the
      isolated compound were determined by MTT and Tripan blue assays. The antioxidant
      and antimicrobial potential of the compound were evaluated by DPPH assay and agar
      dilution method, respectively. The MTT assay results showed that 8-geranyloxy
      psoralen reduced cell viability of Hela and Mc-Coy cell lines with IC(50) values
      of 0.792 and 0.835 mM, respectively. Based on the Tripan blue assay, the compound
      has cytotoxic effects, with an IC(50) value of 1.26 mM for Mc-Coy cell line. The
      compound exhibited weak antioxidant potential, with an RC(50) value of 0.262 mg
      mL(-1) and high antimicrobial effects against Staphylococcus epidermidis and
      Candida kefyr.

PMID- 19844827
TI  - Parthenium management by cultural filtrates of phytopathogenic fungi.
AB  - In the present study, herbicidal activity of culture filtrates of nine
      phytopathogenic fungi, namely, Alternaria alternata (Fr.) Keissl., Drechslera
      australiensis (Bugnicourt) Subramanian & Jain, Drechslera hawaiiensis (Curtis and
      Cooke) Shoemaker, Drechslera biseptata (Saccardo & Roumeguere) Richardson &
      Fraser., Drechslera rostrata (Drechsler) Ricardson & Fraser, Fusarium oxysporum
      (Massey) Synd. & Hans., Fusarium solani (Martius) Saccardo., Monilia stophila
      (Montagne) and Cladosporium sp. (Grey) de Hoff, was evaluated against parthenium
      weed (Parthenium hysterophorus L.). In laboratory bioassays, the effect of
      original (100%) as well as lower concentrations (75, 50 and 25%) of these
      cultural filtrates was studied on germination and early seedling growth of
      parthenium. Cultural filtrates of different concentrations of A. alternata,
      Cladosporium sp. and D. rostrata significantly suppressed the germination of
      parthenium seeds by 70-90, 13-73 and 27-50%, respectively. Cultural filtrates of
      these fungi also exhibited pronounced adverse effects on the seedling root and
      shoot growth. Among other fungal species, cultural filtrates of D. australiensis,
      D. hawaiiensis, F. oxysprium and F. solani significantly reduced the root and
      shoot length of parthenium seedlings. Foliar spray bioassay was performed using
      cultural filtrates of three fungal species, namely A. alternata, F. solani and D.
      rostrata. In this bioassay, three sprays of fungal cultural filtrates, with 4 day
      intervals each, were carried out on 1 and 2 week-old pot-grown seedlings of
      parthenium. Cultural filtrates of all the three fungal species markedly
      suppressed root and shoot growth of parthenium weed.

PMID- 19844828
TI  - Th1/Th2 cytokine production by clove-treated mice.
AB  - Although clove possesses several biological and therapeutic properties, its
      immunomodulatory action has not been fully investigated. The goal of this work
      was to investigate the effect of administration of the water extract of clove
      over a short-term to BALB/c mice on Th1 (IFN-gamma and IL-2) and Th2 (IL-4 and IL
      10) cytokine production. After treatment, spleen cells were aseptically removed
      and cells were stimulated with concanavalin A. Supernatants of cell cultures were
      used for cytokine determination by ELISA. The chemical composition of the extract
      was also carried out, revealing that eugenol(4-allyl-2-methoxyphenol) was the
      major component in our sample. Although the anti-inflammatory action of clove has
      been mentioned, our data showed that clove administration to mice did not
      influence the Th1/Th2 cytokine balance. Further studies dealing with cytokine
      expression and production will provide a better understanding of clove's
      immunomodulatory and anti-inflammatory actions, using different extract
      concentrations and different intake periods.

PMID- 19844829
TI  - Active compounds against tinea pedis dermatophytes from Ageratina pichinchensis
      var. bustamenta.
AB  - Secondary metabolites 5-acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-2,3
      dihydrobenzofurane (1), 5-acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-6
      methoxy-2,3-dihydrobenzofurane (2), espeletone (3), encecalinol (4), O
      methylencecalinol (5), encecalin (6), sonorol (7), taraxerol (8), (+)-beta
      eudesmol (9), and a mixture of beta-sitosterol and stigmasterol, were isolated
      from the aerial parts of Ageratina pichinchensis var. bustamenta. The
      antimicrobial activity of compounds 6, 8 and 9, together with derivatives 9a and
      9b against the most important dermatophytes responsible for tinea pedis
      infection, Trichophyton rubrum and T. mentagrophytes, and against Candida
      albicans and Aspergillus niger were determined, showing that the three natural
      products were active against both Trichophyton species. Ageratina pichinchensis
      var. bustamenta is used in folk medicine to treat skin infections and wounds, and
      this study confirms that the n-hexane extract contains metabolites which are
      responsible for these utilities.

PMID- 19844830
TI  - Feasibility and effectiveness of a brief meditation-based stress management
      intervention for patients diagnosed with or at risk for coronary heart disease: a
      pilot study.
AB  - Extensive research has led to the development of a psychobiological model of
      cardiovascular disease. This model suggests that psychological factors such as
      depression, anxiety, hostility, and stress may affect the development and
      progression of coronary heart disease (CHD). Recent studies have also
      demonstrated that meditation-based stress reduction programs are useful
      interventions for patients with various medical and psychological symptoms. The
      objective of this pilot study was to gather preliminary information regarding the
      feasibility of implementing a brief meditation-based stress management (MBSM)
      program for patients with CHD, and those at high risk for CHD, at a major
      metropolitan hospital that serves a predominately non-local patient population.
      The secondary aim of this study was to investigate the possibility that such an
      intervention might reduce depression, as well as perceived stress, anxiety, and
      hostility, while improving general health scores. The overall feasibility results
      indicate that this MBSM intervention was highly feasible with regard to both
      recruitment and retention of participants. In fact, 40% of patients requested
      further training. In addition, after completion of the 4-week intervention,
      participants reported significant reductions in depression and perceived stress.
      In conclusion, the present study demonstrated that the brief meditation-based
      stress management program was well-received by patients and can successfully be
      used as a supportive program for patients at risk or diagnosed with CHD.

PMID- 19844831
TI  - Knowing a donor and identifying as one: determinants of people's willingness for
      related and anonymous living donation in Australia.
AB  - Although living related donation (LRD) (living donation to a
      genetically/emotionally related recipient) is well established in Australia,
      living anonymous donation (LAD) to a stranger is rare. Given the increasing use
      of LAD overseas, Australia may likely follow suit. Understanding the determinants
      of people's willingness for LAD is essential but infrequently studied in
      Australia. Consequently, we compared the determinants of people's LRD and LAD
      willingness, and assessed whether these determinants differed according to type
      of living donation. We surveyed 487 health students about their LRD and LAD
      willingness, attitudes, identity, prior experience with blood and organ donation,
      deceased donation preference, and demographics. We used structural equation
      modelling (SEM) to identify the determinants of willingness for LRD and LAD and
      paired sample t-tests to examine differences in LRD and LAD attitudes, identity,
      and willingness. Mean differences in willingness (LRD 5.93, LAD 3.92), attitudes
      (LRD 6.43, LAD 5.53), and identity (LRD 5.69, LAD 3.58) were statistically
      significant. Revised SEM models provided a good fit to the data (LRD: chi(2) (41)
      = 67.67, p = 0.005, comparative fit index (CFI) = 0.96, RMSEA = 0.04; LAD: chi(2)
      (40) = 79.64, p < 0.001, CFI = 0.95, RMSEA = 0.05) and explained 45 and 54% of
      the variation in LRD and LAD willingness, respectively. Four common determinants
      of LRD and LAD willingness emerged: identity, attitude, past blood donation, and
      knowing a deceased donor. Religious affiliation and deceased donation preference
      predicted LAD willingness also. Identifying similarities and differences in these
      determinants can inform future efforts aimed at understanding people's LRD and
      LAD willingness and the evaluation of potential living donor motives. Notably,
      this study highlights the importance of people's identification as a living donor
      as a motive underlying their willingness to donate their organs while living.

PMID- 19844832
TI  - A comparison of physical activity-related social-cognitive factors between those
      with type 1 diabetes, type 2 diabetes and diabetes free adults.
AB  - Despite strong evidence supporting the benefits of physical activity in managing
      and preventing diabetes, the majority of Canadians living with or without
      diabetes are insufficiently active to achieve health benefits. The purpose of
      this study was to examine the difference in key physical activity-related,
      psychosocial constructs from major social-cognitive theories/models for
      individuals with type 1 diabetes (n = 695), type 2 diabetes (n = 1540) and those
      without diabetes (n = 829). The relatively similar scores reported for the social
      cognitive constructs between the groups suggest that theoretically driven,
      generic population-based strategies operationalizing key socio-cognitive
      constructs for promoting physical activity may have utility for the general and
      diabetes specific populations. However, both diabetes groups reported
      significantly lower (p < 0.001) response efficacy (benefits of physical activity)
      scores, and higher scores for cons of performing physical activity than the non
      diabetes group (p < 0.001). Further, the type 1 diabetes group had significantly
      higher (p < 0.05) physical activity cons scores than the other two study groups.
      The findings of this study may guide practitioners in designing population-based,
      physical activity programs that capitalize on generic strategies for the general
      and diabetes populations, and identify efforts as to where specific tailoring
      (e.g. emphasizing physical activity benefits) is needed for those living with
      diabetes.

PMID- 19844833
TI  - Physician well being and quality of patient care: an exploratory study of the
      missing link.
AB  - The goal of this article is to explore physicians' perceptions of their
      colleagues' awareness of the link between physician wellness and the quality of
      care they provide to their patients. In addition, we also examine potential
      factors that may be related to physicians' recognition or lack of recognition of
      this link. We rely on qualitative interview data from a sample of 42 physicians
      representing the spectrum of different medical specialties and work settings in a
      single health region in Western Canada. Our findings suggest that many physicians
      believe the link between physicians' well being and the quality of care they
      provide their patients is not necessarily at the forefront of most doctors'
      awareness as they practice medicine on a day-to-day basis. Our study participants
      identified a number of factors that may explain this finding and that reflect two
      broad themes: the culture of medicine and physicians' overwhelming workload. In
      regards to the culture of medicine, the physicians in our study reported how
      doctors view themselves as invincible caregivers first and foremost who must look
      after others before looking after themselves, who believe they do not need help
      from others and who are highly committed to their patients, careers and sense of
      professionalism. In regards to physicians' workloads, our study participants
      identified external pressures in the workplace in terms of how their busy
      schedules and the overwhelming nature of their work are significant deterrents
      that often prevent them from thinking about their own wellness. We discuss how
      the culture of medicine and physicians' workloads deter doctors from recognizing
      signs of unwellness and caring for themselves. We conclude that not only
      individual physicians, but also their peers, their patients, employing
      organizations and the health care system must appreciate and support physicians
      in their efforts to protect and maintain their personal well being.

PMID- 19844835
TI  - Psychological change after aesthetic plastic surgery: a prospective controlled
      outcome study.
AB  - Aesthetic plastic surgery has been long practiced for primarily psychological
      rather than physical benefit to patients. However, evaluation of the
      psychological impact of aesthetic plastic surgery has often been of limited
      methodological rigor in both study design and appropriate measurement. This study
      is intended to evaluate the psychological impact of aesthetic surgery on patients
      seeking such intervention in regard to concerns about breasts, nose or upper
      limbs using standardised psychometric instruments. Participants were recruited
      through the Plastic Surgery Unit (Patients) and general surgery, ENT surgery and
      Maxillo-facial surgery (Comparisons) at a UK General Hospital. Outcome measures
      included the Crown-Crisp Experiential Inventory anxiety scale, Beck Depression
      Inventory and Derriford Appearance Scale-24, a valid and reliable measure of
      distress and dysfunction in relation to self-consciousness of appearance. Data
      were collected pre-operatively (T1) and 3 months post-operatively (T2) for both
      groups. Longitudinal appearance adjustment for the plastic surgery group was also
      assessed at 12 months (T3). Both groups were less depressed and anxious post
      operatively. The improvement in anxiety was significantly greater in the plastic
      surgery group. Body site specific appearance distress was significantly improved
      for the plastics group only, and the level of improvement was related to the body
      site affected.

PMID- 19844834
TI  - A longitudinal analysis of humor coping and quality of life in systemic
      sclerosis.
AB  - A connection between humor and health outcomes is widely assumed but has been
      understudied, particularly in clinical populations. The use of humor as a coping
      mechanism has been suggested as a potential predictor of quality of life (QOL)
      outcomes in chronic disease. This study assessed the relationship between humor
      and physical/mental health variables in a longitudinal study of individuals with
      systemic sclerosis (SSc), a progressive rheumatic disease that can be fatal in
      severe cases. It was hypothesized that humor coping (HC) would be inversely
      associated with disease severity, pain, disability, and psychological distress.
      It was also hypothesized that after implementing the appropriate demographic and
      disease severity controls, HC would predict these outcomes both cross-sectionally
      and longitudinally. Ninety-three participants with SSc received clinical exams
      and completed self-report surveys. The exam and measures were repeated
      approximately 1 year later (n = 74). In bivariate correlational analysis, HC was
      found to be negatively associated with disease severity, pain, disability, and
      distress, as predicted. However, after controlling for covariates in hierarchical
      regression analysis, HC did not significantly predict any of the disease-related
      outcomes, either cross-sectionally or longitudinally. The HC did approach
      significance as a predictor of disability at Time 1, although the effect was
      weak. This study contributes to a growing body of evidence that HC may not be
      directly beneficial to QOL in chronic disease. Although the notion that HC could
      be an inexpensive and accessible point of intervention among the chronically ill
      is appealing, results suggest the relationship is associative and small at best,
      and do not provide evidence supporting the use of humor as a therapeutic
      strategy.

PMID- 19844836
TI  - Resilience in children of parents with mental illness: relations between mental
      health literacy, social connectedness and coping, and both adjustment and
      caregiving.
AB  - This study investigated the relationships between resilience factors (mental
      health literacy, social connectedness, coping strategies) frequently targeted in
      interventions, and both adjustment (depressive symptomatology, life satisfaction,
      prosocial behaviour, emotional/behavioural difficulties) and caregiving outcomes
      in children (12 - 17 years) of a parent with mental illness. Forty-four
      participants completed questionnaires. Correlations showed weak support for the
      predicted beneficial associations of mental health literacy with caregiving and
      adjustment, stronger support for the beneficial relationships between social
      connectedness and adjustment, and strong support for the adverse links of
      disengagement and involuntary coping strategies with adjustment and caregiving.
      Findings suggest that some resilience factors have a differential impact on
      adjustment and caregiving, and support the focus of interventions on modifying
      resilience factors.

PMID- 19844837
TI  - Attachment style and alliance in patients with diabetes and healthcare
      professionals.
AB  - Avoidant attachment has been found to impair attendance at appointments and
      treatment adherence of patients with diabetes, but the role of staff-patient
      relationships has not been explored. This study investigates whether attachment
      influences the quality of alliance between patients with diabetes and healthcare
      professionals. Patient avoidance was significantly associated with difficulties
      in therapeutic alliance. Further research is required to establish whether
      therapeutic alliance, underpinned by attachment, influences treatment adherence
      and to investigate ways of promoting collaboration.

PMID- 19844838
TI  - Workplace phobia--a first explorative study on its relation to established
      anxiety disorders, sick leave, and work-directed treatment.
AB  - Workplace phobia is defined as a phobic anxiety reaction with symptoms of panic
      occurring when thinking of or approaching the workplace. People suffering from
      workplace phobia regularly avoid confrontation with the workplace and are often
      on sick leave. The specific characteristics of workplace phobia are investigated
      empirically in comparison to established anxiety disorders. Two hundred thirty
      patients from an inpatient psychosomatic rehabilitation hospital were interviewed
      concerning workplace phobia and established anxiety disorders. Additionally, the
      patients filled in self-rating questionnaires on general and workplace phobic
      symptom load. Subjectively perceived degree of work load, sick leave, and therapy
      participation were assessed. Participants with workplace phobia reached
      significantly higher scores in workplace phobia self-rating than did participants
      with established anxiety disorders. A similar significant difference was not
      found concerning the general psychosomatic symptom load. Workplace phobics were
      more often on sick leave than patients with established anxiety disorders.
      Workplace phobia can occur as an alonestanding anxiety disorder. It has an own
      clinical value due to its specific consequences for work participation. Workplace
      phobia requires special therapeutic attention and treatment instead of purely
      'sick leave' certification.

PMID- 19844839
TI  - Validation of the SF-36 in Jamaicans with sickle-cell disease.
AB  - Quality-of-life (QOL) measurements are becoming a vital part of health outcome
      appraisal. Sickle-cell disease (SCD) places a substantial burden on those
      afflicted. No QOL measure has been validated for use in Jamaica. The SF-36
      version 2 was administered to two samples of patients with SCD: the 'Cohort' (n =
      233), and the 'Main' samples (n = 256). All patients were also administered the
      World Health Organization Quality of Life-Bref (WHOQOL-Bref), Flanagan's Quality
      of-Life Scale (QOLS), and the UCLA Loneliness Scale. All measures were found to
      be reliable with coefficient alphas' ranging from 0.70 to 0.93. The total SF-36
      score showed a strong positive correlation with the total WHOQOL-Bref (0.78) and
      a moderate one with the total QOLS score (0.57). The correlations of the total
      scores from the SF-36 scale with those from the Loneliness Scale were negative
      but moderate in size (-0.59). This study provides fair evidence for the
      concurrent, and some evidence for the discriminant, validity of the SF-36 in
      Jamaicans with SCD.

PMID- 19844840
TI  - World Health Organization quality of life instrument-brief and Short Form-36 in
      patients with coronary artery disease: do they measure similar quality of life
      concepts?
AB  - This study aimed to assess the validity and reliability of World Health
      Organization Quality of Life Instrument (WHOQOL)-brief and SF-36 in patients with
      coronary artery disease (CAD). Considering that depression is known to be
      associated with bad outcomes in CAD and it is highly associated with poor Quality
      of Life (QOL), we tested the correlation between WHOQOL and SF-36 and an
      instrument to screen depressive symptoms. It is a cross-sectional survey
      conducted in 103 patients with documented CAD. QOL was measured through WHOQOL
      brief and SF-36 and depressive symptoms were assessed by the Beck Depression
      Inventory (BDI). To evaluate convergent validity, the correlations between both
      QOL assessment instruments were examined; discriminant validity was assessed
      through BDI and QOL instruments correlations. Coefficient Cronbach's alpha was
      used to test reliability. Percentages of floor and ceiling effects were higher in
      SF-36 scores than the WHOQOL-brief ones. Although WHOQOL-brief showed a maximum
      of 1% of floor effect and 9% of ceiling effect, SF-36 presented 40 and 32%,
      respectively. Internal consistency reliability ranged from 0.65 to 0.85 for the
      WHOQOL-brief and 0.57 to 0.89 for the SF-36. Correlations between subscales of
      WHOQOL-brief and BDI ranged from -0.74 to -0.61 and correlations between
      subscales of SF-36 and BDI ranged from -0.68 to -0.26. SF-36 and WHOQOL-brief
      seem to be valid and consistent QOL measures in patients with CAD. Researchers
      should define the aims of their studies before choosing which instrument to use,
      because they appear to measure different constructs of QOL.

PMID- 19844842
TI  - The synchronization of plan activations and emotion-abstraction patterns in the
      psychotherapeutic process: a single-case study.
AB  - The question of whether the dynamic of interpersonal plans in the
      psychotherapeutic process is reflected in the emotion-abstraction (EA) patterns
      (relaxing, reflecting, experiencing, connecting) described by Mergenthaler (e.g.,
      2008) was examined in a single-case study. The activation of interpersonal plans
      was encoded in 10-s intervals by means of sequential plan analysis on the basis
      of video recordings. The EA patterns were identified in 2-min intervals on the
      basis of a transcript of the nine-session short-term therapy. The hypothesis that
      the dynamic complexity of plan activation time series of the patient increases
      during intensified phases of the EA pattern connecting was examined and
      confirmed. This can be considered an indicator for the occurrence of critical
      instabilities in the environment of order transitions in the direction of more
      strongly integrated states of processing.

PMID- 19844843
TI  - Psychotherapeutic process of cognitive-behavioral intervention in HIV-infected
      persons: results from a controlled, randomized prospective clinical trial.
AB  - The aim of this exploratory study was to examine the possible mechanisms of
      behavioral change in a cognitive-behavioral intervention supporting medication
      adherence in HIV-infected persons. A total of 60 persons currently under medical
      treatment were randomized to psychotherapy or usual care and were compared with a
      sociodemographically matched group of general psychotherapy clients. Outcome
      measures included therapy adherence using medication event-monitoring system
      psychotherapeutic processes and changes of experience and behavior. The general
      psychotherapy group was initially more distressed than HIV psychotherapy patients
      and reached higher levels of psychotherapeutic effect. In the HIV psychotherapy
      patients, a significant effect was found for maintaining adherence to medical
      treatment (Weber et al., 2004). These findings show that psychotherapy is a
      beneficial intervention for HIV-infected persons, and therapeutic alliance and
      activation of resources do not differ from a general psychotherapy treatment.
      Differential effects were detected for specific process variables, namely problem
      actuation.

PMID- 19844844
TI  - The influence of psychodynamically oriented therapists' attachment
      representations on outcome and alliance in inpatient psychotherapy [corrected].
AB  - The Adult Attachment Interview (AAI) was used to study 31 psychotherapists who
      treated 1,381 patients in intensive multimodal inpatient psychotherapy. AAI
      dimensional ratings of security versus insecurity and dismissiveness versus
      preoccupation were used to predict alliance and outcome via multilevel regression
      techniques (hierarchical linear modeling). There were no main effects of
      therapists' attachment dimensions. However, higher attachment security of the
      therapist was associated with both better alliance and outcome in more severely
      impaired patients. Implications of the findings as well as limitations of the
      study are discussed.

PMID- 19844846
TI  - Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual
      meeting. Part 1. 11-15 September 2009, San Francisco, CA, USA.
AB  - The Interscience Conference on Antimicrobial Agents and Chemotherapy held in San
      Francisco included topics covering new therapeutic developments for the treatment
      of infectious diseases. This conference report highlights selected presentations
      on a beta-cyclodextrin derivative for the treatment of Staphylococcus aureus
      infections, a type 3 secretion system inhibitor for the treatment of Pseudomonas
      aeruginosa infections, a small-molecule inhibitor of the fungal Hos2 HDAC, a TLR9
      agonist used as an adjuvant, a CMV vaccine, a glycopeptide-cephalosporin
      heterodimer antibiotic, a topical quinolone for the treatment of complicated skin
      and skin structure infections, a broad-spectrum glycylcycline antibiotic and an
      HCV RNA replication inhibitor. Investigational drugs discussed include IB-201
      (Innovative Biologics Inc), MBX-1641 (Microbiotix Inc), MGCD-290 (MethylGene
      Inc), agatolimod (Coley Pharmaceutical Group Inc/Pfizer Inc/GlaxoSmithKline
      plc/Merck & Co Inc/Dynavax Technologies Corp/Novartis AG/Emergent BioSolutions
      Inc), TD-1792 (Theravance Inc), ozenoxacin (Ferrer Internacional SA/Maruho Co
      Ltd/Toyama Chemical Co Ltd) and ATI-0810 (Arisyn Therapeutics Inc).

PMID- 19844845
TI  - Social approach to pain in laboratory mice.
AB  - It has been recently demonstrated that pain behavior in the mouse can be
      modulated by the presence of a conspecific, but what remains unclear is whether
      such pain behavior can serve the function of soliciting social approach. Using a
      novel social approach paradigm, we tested mice in various dyadic or triadic
      conditions, including "jailed" mice-some in pain via intraperitoneal injection of
      0.9% acetic acid-and test mice free to approach or avoid the jailed mice. We
      observed a sex-specific effect whereby female, but not male, test mice approached
      a familiar same-sex conspecific in pain more frequently than an unaffected
      familiar or unfamiliar, but affected, conspecific. Despite a substantial
      literature emphasizing oxytocin's role in affiliative and pair-bonding behavior,
      this effect was also observed in female mice lacking the oxytocin receptor,
      suggesting that pain-related social approach may not be mediated by oxytocin.
      Furthermore, we found that the frequency of contact by the test mouse was
      negatively correlated with the pain behavior of the jailed mouse, suggesting that
      proximity of a familiar unaffected conspecific may have analgesic properties.

PMID- 19844847
TI  - Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual
      meeting. Part 2. 12-15 September 2009, San Francisco, CA, USA.
AB  - The Interscience Conference on Antimicrobial Agents and Chemotherapy held in San
      Francisco included topics covering new therapeutic developments for the treatment
      of infectious diseases. This conference report highlights selected presentations
      on several antibiotics in development including a broad-spectrum penem beta
      lactam antibiotic, a novel siderophore monobactam, as well as other novel
      antibiotics. Investigational drugs discussed include sulopenem and sulopenem
      etzadroxil (both Pfizer Inc), BAL-30072 (Basilea Pharmaceutica International
      Ltd), TP-120 and TP-787 (both Tetraphase Pharmaceuticals Inc), NAI-107 (New Anti
      Infectives Consortium/NexThera Biosciences) and ABI-200 (AdRem Biotech/US
      Department of Agriculture).

PMID- 19844848
TI  - Biomarkers in Clinical Trials--SMi Conference. 23-24 September 2009, London, UK.
AB  - The Biomarkers in Clinical Trials conference, held in London, included topics
      covering new developments in the field of biomarkers. This conference report
      highlights selected presentations on the definition of biomarkers, the use of
      biomarkers to support decisions in drug development and to improve treatment
      outcomes, and the aims of the Biomarkers Consortium. A case study of the
      investigational drug selumetinib (AstraZeneca plc) is also discussed.

PMID- 19844849
TI  - European Society of Cardiology--2009 annual congress. 31 August - 2 September
      2009, Barcelona, Spain.
AB  - The European Society of Cardiology Annual Congress, held in Barcelona, included
      topics covering new therapeutic developments in the field of cardiovascular
      disease. This conference report highlights selected presentations on the
      development and progression of atherosclerosis, imaging techniques for treating
      atherosclerosis and clinical trials of treatments for cardiovascular disease.
      Investigational drugs discussed include ticagrelor (AstraZeneca AG).

PMID- 19844850
TI  - Drug Delivery--Select Biosciences Inaugural Summit. 2-4 September 2009, London,
      UK.
AB  - The Drug Delivery - Select Biosciences Inaugural Summit, held in London, included
      topics covering recent advances in delivery systems for the controlled release of
      small-molecule drugs and larger biologicals, particularly nucleic acids, peptides
      and proteins. This conference report highlights selected presentations on image
      guided drug delivery; the delivery of nucleic acids, peptoids, peptides and
      proteins; and formulation and solubility research. Technological approaches
      discussed include polymeric nanomedicines, nucleic acid-based therapeutics, the
      solid-dose injector Glide SDA, polyamino acid-based nanocarriers, polylactide
      glycolic acid microspheres, and enhanced biopharmaceutical products such as
      CriticalMix and CriticalSorb, PolyPEG, microspheres and cell-penetrating
      peptides.

PMID- 19844851
TI  - The British Pharmaceutical Conference 2009. 6-9 September 2009, Manchester, UK.
AB  - The British Pharmaceutical Conference 2009, held in Manchester, included topics
      covering new therapeutic and technological developments in the field of anti
      infectives. This conference report highlights selected presentations on anti
      infective drug discovery, treatment paradigms for bacterial infections, adaptive
      immunotherapy, point-of-care diagnostics, and the use of nanosensors for
      detecting drug-resistant bacteria.

PMID- 19844852
TI  - BirdFlu2009: Avian Influenza and Human Health. 9-10 September 2009, Oxford, UK.
AB  - The BirdFlu2009 meeting entitled Avian Influenza and Human Health, held in
      Oxford, included topics covering new developments in the control of seasonal,
      avian and swine influenza virus infection, with a focus on the human-animal
      interface. This conference report highlights selected presentations on sialidase
      therapy for influenza infection, the use of IVIgs to study antibody diversity and
      reactivity, detecting oseltamivir carboxylate in waste water, H5N1 infection in
      Egyptian children, preparedness for an influenza pandemic and an indirect
      sandwich ELISA to detect H5 avian influenza virus. Investigational drugs
      discussed include NEX-DAS-181 (NexBio Inc) and MVA-NP-M1 (The Edward Jenner
      Institute for Vaccine Research).

PMID- 19844853
TI  - Perspectives in Lung Cancer--Third Asian-pacific Conference. 11-12 September
      2009, Bangkok, Thailand.
AB  - The Third Asian-Pacific Conference on Perspectives in Lung Cancer held in Bangkok
      included topics covering new therapeutic developments in the field of lung
      cancer. This conference report highlights selected presentations on the
      management and maintenance of lung cancer from an Asian perspective.

PMID- 19844854
TI  - Americas Antibody Congress 2009. 21-23 September 2009, Washington DC, USA.
AB  - The Americas Antibody Congress 2009, held in Washington DC, included topics
      covering new state-of-the-art advances in antibody therapeutics. This conference
      report highlights selected presentations on enhanced antibody functionality,
      bispecific antibodies and antibody-drug conjugates. Technological approaches
      discussed include Potelligent technology from BioWa Inc, stability-engineered
      antibodies and BiTE antibodies.

PMID- 19844855
TI  - Recent Developments in Wound Management: intelligent biomaterials to novel
      antimicrobials. 24 September 2009, London, UK.
AB  - The Recent Developments in Wound Management conference, held in London, included
      topics covering new developments in the field of wound treatment, relating to
      infection management. This conference report highlights selected presentations on
      the prevalence of pathogenic microorganisms, and the development of anti
      infective biomaterials, antimicrobial biocides and novel types of antimicrobial
      agents.

PMID- 19844856
TI  - Bacterial adhesion--a source of alternate antibiotic targets.
AB  - The prevalence of antibiotic resistance among microorganisms that cause
      infectious diseases has resulted in the need to devise new strategies for the
      development of novel therapeutics. In an effort to thwart antibiotic resistance,
      novel therapeutics are being developed that target bacterial virulence factors as
      an alternative to traditional antibiotics, which target essential microbial
      processes, thereby promoting bacterial evolution and resulting in resistance.
      While many antivirulence targets exist, this feature review focuses on adhesion
      as an antivirulence target, using pili of uropathogenic Escherichia coli as a
      model system. The two strategies of drug development discussed in this review
      involve the inhibition of bacterial binding to the host tissue by the addition of
      exogenous sugars, and the disruption of chaperone-usher (CU) pilus assembly
      through the disruption of protein-protein interactions. However, because of the
      commonality of adhesion to infectious disease processes and CU pili to many
      pathogens, the two strategies are translatable to a multitude of organisms.

PMID- 19844857
TI  - The role of mitochondrial dysfunction and drug safety.
AB  - Mitochondria are the energy powerhouses of cells and are essential for cell
      survival. Evidence demonstrates that mitochondria are the off-targets of many
      drugs belonging to a diverse array of classes. This feature review discusses the
      mechanisms by which drugs impair mitochondrial function, and describes some of
      the high-throughput methods being used to screen for drug-induced mitochondrial
      impairment.

PMID- 19844858
TI  - Apricoxib, a COX-2 inhibitor for the potential treatment of pain and cancer.
AB  - Apricoxib (CS-706), a small-molecule, orally active, selective COX-2 inhibitor,
      is under development by Tragara Pharmaceuticals Inc as an analgesic and anti
      inflammatory agent, and also for its anticancer potential. The compound has
      desirable pharmacokinetic parameters, and has demonstrated good gastrointestinal
      tolerability and safety in preclinical studies and clinical trials. Phase IIa
      trial data indicated that apricoxib was a potent analgesic in the treatment of
      pain in postoperative dental surgery. At the time of publication, phase II trials
      assessing apricoxib in combination with anticancer drugs in patients with breast,
      lung and pancreatic cancer were ongoing. Evidence for the anticancer activity of
      oral apricoxib appears to be highly promising. However, the market success of
      apricoxib will depend mainly on long-term safety trials, which are needed to
      establish the cardiovascular safety of the drug when administered alone or in
      combination with other agents in cancer chemotherapy.

PMID- 19844859
TI  - Effect of ghrelin and thyrotropin-releasing hormone on prolactin secretion in
      normal women.
AB  - It is known that ghrelin stimulates the secretion of prolactin in women. The aim
      of this study was to examine the effect of exogenous thyrotropin-releasing
      hormone (TRH) on ghrelin-induced prolactin release. Ten healthy normally cycling
      women were studied in four menstrual cycles. The women were injected
      intravenously in late follicular phase (follicle size 16-17 mm) with a single
      dose of normal saline (cycle 1), ghrelin (1 microg/kg) (cycle 2), thyrotropin
      releasing hormone (200 microg) (cycle 3), and ghrelin plus thyrotropin-releasing
      hormone (cycle 4). Blood samples in relation to saline or drugs injection (time
      0) were taken at -15, 0, 15, 30, 45, 60, 75, 90, and 120 min. The prolactin and
      growth hormone responses were assessed. After ghrelin administration (cycles 2
      and 4), plasma ghrelin, serum prolactin, and growth hormone levels increased
      rapidly, peaking at 15-30 min (p<0.001). The injection of thyrotropin-releasing
      hormone (cycle 3) stimulated prolactin secretion markedly (p<0.001), but reduced
      growth hormone levels significantly (p<0.05). Ghrelin induced a smaller prolactin
      increase than thyrotropin-releasing hormone (p<0.05). The combination of ghrelin
      and thyrotropin-releasing hormone induced a similar increase in prolactin levels
      as with thyrotropin-releasing hormone alone. No changes in growth hormone and
      prolactin levels were seen after saline injection. These results demonstrate that
      the stimulating effect of ghrelin on prolactin secretion is not additive with
      that of thyrotropin-releasing hormone.

PMID- 19844860
TI  - Goji (Lycium barbarum and L. chinense): Phytochemistry, pharmacology and safety
      in the perspective of traditional uses and recent popularity.
AB  - Since the beginning of this century, Goji berries and juice are being sold as
      health food products in western countries and praised in advertisements and in
      the media for well-being and as an anti-aging remedy. The popularity of Goji
      products has rapidly grown over the last years thanks to efficient marketing
      strategies. Goji is a relatively new name given to Lycium barbarum and L.
      chinense, two close species with a long tradition of use as medicinal and food
      plants in East Asia, in particular in China. While only L. barbarum is officinal,
      the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both
      species are used in the folk medicine. We review here the constituents,
      pharmacology, safety, and uses of L. barbarum and L. chinense with consideration
      to the different parts of the plant. Investigations of the fruit have focused on
      proteoglycans, known as " Lycium barbarum polysaccharides", which showed
      antioxidative properties and some interesting pharmacological activities in the
      context of age related diseases such as atherosclerosis and diabetes. As to the
      root bark, several compounds have demonstrated a hepatoprotective action as well
      as inhibitory effects on the rennin/angiotensin system which may support the
      traditional use for the treatment of hypertension. While there are no signs of
      toxicity of this plant, two cases of possible interaction with warfarin point to
      a potential risk of drug interaction. In view of the available pharmacological
      data and the long tradition of use in the traditional Chinese medicine, L.
      barbarum and L. chinense certainly deserve further investigation. However,
      clinical evidences and rigorous procedures for quality control are indispensable
      before any recommendation of use can be made for Goji products.

PMID- 19844861
TI  - Sodium bisulfite improves rhizome yield and quality in Paris polyphylla.
AB  - Rhizomes of the perennial herb Paris polyphylla have been used in traditional
      Chinese medicine for hundreds of years. Agricultural production of the rhizomes
      requires 7-10 years, which is too long to meet the demand of the medicinal
      industry. Therefore, studies on improving the yield of the herb and shortening
      the culturing period are imperative. The present work aimed to investigate the
      effect of sodium bisulfite (NaHSO (3)) on rhizome yield and quality, as well as
      some related metabolic features of P. polyphylla. The rhizome yield was improved
      by NaHSO (3) treatment in long-term experiments conducted during 2006 and 2007,
      with 2 mM NaHSO (3) giving the highest yield. HPLC analysis revealed that NaHSO
      (3) treatment increased the total saponin content (49 %), including three
      pennogenin glycosides and two diosgenin glycosides. In a short-term experiment,
      NaHSO (3) treatment resulted in an enhanced net photosynthetic rate (Pn) for
      about 4 days without significant changes in the chlorophyll or carotenoid
      content. The total soluble sugars and sucrose contents in the leaves also
      significantly increased after 2 mM NaHSO (3) treatment, whereas the starch
      content changed only slightly. The activities of the enzymes involved in ammonium
      assimilation (glutamine synthetase [GS] and glutamate dehydrogenase [GDH]) were
      not significantly influenced. In a long-term experiment, chlorophylls and
      carotenoids were not significantly affected, and neither was the starch content
      in leaves, but the total soluble sugars and sucrose contents in leaves increased
      significantly. The NaHSO (3) treatment significantly increased GS and GDH
      activities. These results indicate that NaHSO (3) treatment improved the rhizome
      yield in P. polyphylla, not only through enhancement of Pn but also by improving
      carbohydrate accumulation and ammonium assimilation. The increased saponin
      content after NaHSO (3) treatment was indicative of high rhizome quality.

PMID- 19844862
TI  - Physicochemical stability and biological activity of Withania somnifera extract
      under real-time and accelerated storage conditions.
AB  - Stability testing at preformulation stages is a crucial part of drug development.
      We studied physicochemical stability and biological activity of Withania
      somnifera (ashwagandha) dried root aqueous extract during six months real-time
      and under accelerated storage conditions. The characteristic constituents of
      ashwagandha roots include withanolides such as withaferin A and withanolide A. We
      modified and validated the HPLC-DAD method for quantitative measurement of
      withanolides and fingerprint analysis. The results suggest a significant decline
      in withaferin A and withanolide A content under real and accelerated conditions.
      The HPLC fingerprint analysis showed significant changes in some peaks during
      real and accelerated storage (> 20 %). We also observed incidences of clump
      formation and moisture sensitivity (> 10 %) under real-time and accelerated
      storage conditions. These changes were concurrent with a significant decline in
      immunomodulatory activity (p < 0.01) during the third month of the accelerated
      storage. Thus, adequate control of temperature and humidity is important for WSE
      containing formulations. This study may help in proposing suitable guidance for
      storage conditions and shelf life of ashwagandha formulations.

PMID- 19844863
TI  - Acetogenin and prenylated flavonoids from Helminthostachys zeylanica with
      inhibitory activity on superoxide generation and elastase release by neutrophils.
AB  - One new acetogenin, 6-hydroxy-8-pentadecyloxocane-2,7-dione ( 1), and four new
      prenylated flavonoids, 4''a,5'',6'',7'',8'',8''a-hexahydro-5,3',4'-trihydroxy
      5'',5'',8''a-trimethyl-4 H-chromeno[2'',3'':7,6]flavone ( 2),
      4''a,5'',6'',7'',8'',8''a-hexahydro-5,3',4',-trihydroxy-5'',5'',8''a-trimethyl-4
      H-chromeno[2'',3'':7,8]flavone ( 3), 2-(3,4-dihydroxyphenyl)-6-((2,2-dimethyl-6
      methylenecyclohexyl)methyl)-5,7-dihydroxy-chroman-4-one ( 4), and 2-(3,4
      dihydroxy-2-[(2,6,6-trimethylcyclohex-2-enyl)methyl]phenyl)-3,5,7-trihydroxy-4 H
      chromen-4-one ( 5), together with six known compounds, were isolated and purified
      from the rhizomes of Helminthostachys zeylanica by column chromatography and high
      performance liquid chromatography (HPLC) via bioactivity-guided fractionation
      isolation. The structures of the new isolates were elucidated by spectroscopic
      methods. Compounds 1, 3, and 5 showed inhibitory activities on either superoxide
      anion generation or elastase release by human neutrophils in response to formyl-L
      methionyl-L-leucyl-L-phenylalanine/cytochalasin B (FMLP/CB).

PMID- 19844864
TI  - Identification of Lonicera japonica by PCR-RFLP and allele-specific diagnostic
      PCR based on sequences of internal transcribed spacer regions.
AB  - The flower buds of Lonicera japonica Thunb. are widely used in Chinese medicine
      for their anti-inflammatory prosperities. Some closely related species of L.
      japonica which have similar morphology but weaker biological activity are also
      used medicinally. The discrimination of L. japonica from its adulterants is
      currently limited to methods of morphology and chemical fingerprinting. The
      analysis of sequence variation in the nuclear ribosomal DNA (nrDNA) internal
      transcribed spacer (ITS) has recently become an effective method for
      identification of medicinal herbs. In the present study, we found that nrDNA ITS
      sequences differ significantly between L. japonica and the 4 tested adulterant
      species. We identified a distinctive site which can be digested by restriction
      endonuclease ECO52 I and designed a pair of allele-specific primers for
      diagnostic PCR on the nrDNA ITS2 region. These two techniques provide accurate,
      effective, and rapid approaches to distinguish L. japonica from closely related
      species.

PMID- 19844865
TI  - Successful isolation and PCR amplification of DNA from National Institute of
      Standards and Technology herbal dietary supplement standard reference material
      powders and extracts.
AB  - Twenty-four herbal dietary supplement powder and extract reference standards
      provided by the National Institute of Standards and Technology (NIST) were
      investigated using three different commercially available DNA extraction kits to
      evaluate DNA availability for downstream nucleotide-based applications. The
      material included samples of Camellia, Citrus, Ephedra, Ginkgo, Hypericum,
      Serenoa, And Vaccinium. Protocols from Qiagen, MoBio, and Phytopure were used to
      isolate and purify DNA from the NIST standards. The resulting DNA concentration
      was quantified using SYBR Green fluorometry. Each of the 24 samples yielded DNA,
      though the concentration of DNA from each approach was notably different. The
      Phytopure method consistently yielded more DNA. The average yield ratio was 22 :
      3 : 1 (ng/microL; Phytopure : Qiagen : MoBio). Amplification of the internal
      transcribed spacer II region using PCR was ultimately successful in 22 of the 24
      samples. Direct sequencing chromatograms of the amplified material suggested that
      most of the samples were comprised of mixtures. However, the sequencing
      chromatograms of 12 of the 24 samples were sufficient to confirm the identity of
      the target material. The successful extraction, amplification, and sequencing of
      DNA from these herbal dietary supplement extracts and powders supports a
      continued effort to explore nucleotide sequence-based tools for the
      authentication and identification of plants in dietary supplements.

PMID- 19844866
TI  - Cytotoxic activity and G1 cell cycle arrest of a Dienynone from Echinacea
      pallida.
AB  - In the present study, a further investigation of the cytotoxic activity of an
      acetylenic constituent of Echinacea pallida roots, namely, pentadeca-(8 Z,13 Z)
      dien-11-yn-2-one, was performed, revealing a concentration-dependent cytotoxicity
      on several human cancer cell lines, including leukemia (Jurkat and HL-60), breast
      carcinoma (MCF-7), and melanoma (MeWo) cells. As part of its mechanism of action,
      the ability of this constituent to arrest the cell cycle in the G1 phase was
      demonstrated on HL-60 cells. Furthermore, a stability test of the target compound
      over 72 h was carried out, indicating that the cytotoxic activity can be
      attributed mainly to the genuine, not oxidized, molecule.

PMID- 19844867
TI  - Two new peltogynoids from Acacia nilotica Delile with kinase inhibitory activity.
AB  - Two new peltogynoids, acanilol (1) and acanilol B (2), were isolated from the
      stem bark of Acacia nilotica (L.) Delile, together with the known triterpene
      lupenone. The structures of the new compounds were established on the basis of
      their spectral data, mainly UV, NMR, and mass spectrometry. The new compounds
      were tested as kinase inhibitors against CDK1, GSK3, CK1, and DYRK1A, and
      acanilol B was identified as a DYRK1A inhibitor, with an IC(50) of 19 microM.

PMID- 19844868
TI  - [Prevention and health promotion--what about health policy? Historical and
      present day perspectives].
AB  - Three "main public health revolutions" have been described in the history of
      public health -the fight against communicable diseases by means of hygiene and
      bacteriology, the struggle against risk factors by early diagnosis and behaviour
      modification and the vitalisation of health resources by health promotion. This
      does not say much about governmental or societal strategies and their successes.
      In this article the development of health policies is outlined from the end of
      the 18 (th) century until today. What kind of state-run or social
      responsibilities have been defined? Have health policies been supported,
      constrained or pursued by the state? Has state control restricted the right of
      personal freedom? Public health measures were often claimed by social reformers
      and only hesitantly adopted by state action. It was under the special conditions
      of National Socialism in Germany that the "Volksgesundheit" became a national
      objective, achieved by selection and enforced even against the will of the
      persons concerned. In the aftermath, personal freedom thus acquired a high
      priority in health policy debates. Meanwhile this view seems to be questioned.

PMID- 19844869
TI  - [German diagnosis related groups (G-DRG): results of sociomedical expertises in
      acute cerebrovascular diseases].
AB  - Acute cerebrovascular diseases are the most common cause for permanent disability
      and the most expensive diseases in industrialised countries. Therefore, all
      sociomedical DRG expertises (n=7 227, 94.15% initial expertises, 5.85% subsequent
      expertises) of the Medical Services of the German Statutory Sickness Insurance
      (MDK) Berlin-Brandenburg in the years 2005-2008 concerning correct G-DRG coding
      in acute cerebrovascular diseases were evaluated using descriptive statistics.
      Changes of major diagnostic category (MDC) were done in 4.35% of initial and in
      2.84% of subsequent expertises, G-DRG changes without MDC change in 10.41% of
      initial and 14.42% of subsequent expertises, changes of severity code within one
      G-DRG in 25.81% of initial and 24.82% of subsequent expertises. No change of cost
      weight was seen in 59.44% of initial and 57.92% of subsequent expertises. In
      1.29% of initial and 1.89% of subsequent expertises, the cost weight given by the
      hospital was lower than the cost weight determined by MDK. In 39.27% of initial
      and in 40.19% of subsequent expertises the cost weight given by the hospital was
      higher than the cost weight determined by MDK. Longitudinal comparisons of the
      years 2005-2008 showed an increase of changes of severity codes and of the cases
      with cost weight given by the hospital being higher than the cost weight
      determined by MDK. A decrease was seen in MDC changes, in G-DRG changes without
      MDC change and of cases with unchanged cost weights. The results point at
      learning effects considering the right coding as well as at the existence of
      further room for improvement concerning the quality of coding after hospital
      treatment of acute cerebrovascular diseases.

PMID- 19844873
TI  - [Update: diagnosis and therapy of tropical diseases -- part 2].

PMID- 19844874
TI  - Tissue reaction to implants of different metals: a study using guide wires in
      cannulated screws.
AB  - Cannulated screws, along with guide wires, are typically used for surgical
      fracture treatment in cancellous bone. Breakage or bending deformation of the
      guide wire is a clinical concern. Mechanically superior guide wires made of Co-Cr
      alloys such as MP35N and L605 may reduce the occurrence of mechanical failures
      when used in combination with conventional (316L stainless steel) cannulated
      screws. However the possibility of galvanic or crevice corrosion and adverse
      tissue reaction, exists when using dissimilar materials, particularly in the
      event that a guide wire breaks, and remains in situ. Therefore, we designed an
      experiment to determine the tissue reaction to such an in vivo environment.
      Implant devices were designed to replicate a clinical situation where dissimilar
      metals can form a galvanic couple. Histological and SEM analyses were used to
      evaluate tissue response and corrosion of the implants. In this experiment, no
      adverse in vivo effects were detected from the use of dissimilar materials in a
      model of a broken guide wire in a cannulated screw.

PMID- 19844875
TI  - [Frequent drug interactions in old age].

PMID- 19844877
TI  - [What is your diagnosis? Hyperkalemia in acute kidney failure in known chronic
      kidney failure].

PMID- 19844878
TI  - [Perioperative antiplatelet therapy of patients with coronary stents].
AB  - The most feared complication after coronary stent implantation is the acutely
      occurring stent thrombosis, which usually leads to a myocardial infarction with
      its relatively high mortality. Dual antiplatelet therapy with acetylsalicylic
      acid and clopidogrel is currently the standard therapy after coronary stent
      implantation to prevent a life-threatening stent thrombosis. Surgery appears to
      increase the risk of stent thrombosis, myocardial infarction, and death,
      particularly when patients undergo surgery early after stent implantation. The
      incidence of complications is further increased when dual-antiplatelet therapy is
      discontinued preoperatively. This article reviews the current data of
      perioperative problems in patients after percutaneous coronary intervention.

PMID- 19844879
TI  - [Basics of gerontopharmaceutic therapy and the therapy of agitation in old age].
AB  - The biggest problem of gerontopharmaceutic therapy is polypharmacy, because it
      potentiates side effects and malcompliance. Best practice today includes
      instruction of long time patients in medication self management, which includes
      regular use of detailed taken medication lists. In gerontopharmaceutic therapy
      the following substances should be avoided: anticholinergics, dopamin receptor
      stimulants, long acting oral antidiabetics, benzodiazepine (other then for
      substitution in low dose dependency, in anaesthesia or in palliative situations)
      and neuroleptics (other then for psychotic symptoms). In unspecific agitation
      with or without dementia the measure of first choice is adaption of the milieu,
      which may be supported by the prescription of a sedative non tricyclic
      antidepressive medication.

PMID- 19844880
TI  - [News in emergency medicine 2009].
AB  - The field of Emergency Care Medicine is a very dynamic part of the Medical
      Science. That is why there is a huge amount of publications on this topic every
      year. This article is my personal selection of recently published scientific work
      on pulmonary embolism, classification of circulatory shock, betablockers in acute
      decompensated heart failure, advanced cardiac life support, subarachnoid
      hemorrhage, inhalation therapy with ipratropium-bromide, community acquired
      pneumonia, diverticulosis, gout and pancreatitis. Last but not least there is a
      choice of prophylactic interventions, you might not yet be aware of. Some of the
      discussed publications may help you manage the next patient you'll encounter,
      when you're on call next time.

PMID- 19844881
TI  - [Comment with the (age-) psychiatric viewpoint].

PMID- 19844882
TI  - [Comment on the off-label use of neuroleptics in nursing homes].

PMID- 19844883
TI  - [Recognition and assessment of celiac disease in children and adults: summary of
      NICE guideline].

PMID- 19844884
TI  - [Cognitive impairment not due to dementia].
AB  - A 55 years old woman lived with the parents until they died. Recently, she
      refused to open her apartment for necessary repairs. An examination was possible
      only after police opened the apartment. She is in excellent physical health, has
      intact memory functions but reduced executive abilities. She has no delusion, but
      excessive fear from strangers as taught by her parents. The clinical impression
      of a debility is confirmed by enquiry at her relatives. The installation of a
      guardianship can give the necessary support for daily life.

PMID- 19844886
TI  - [Answers to questions on needlestick injuries from PRAXIS No. 20].

PMID- 19844887
TI  - [Physicians -- painting riddle].

PMID- 19844888
TI  - [Physicians -- Art column].

PMID- 19844889
TI  - Heterotypic cell-cell interaction on micropatterned surfaces.
AB  - PURPOSE: The aim of this paper was to study the influence of chemical and
      topographical signals on cell behavior and to obtain a heterotypic cell-cell
      interaction on microstructured domains. METHODS: The polysaccharide hyaluronic
      acid (Hyal) was photoimmobilized on glass surfaces in order to obtain a pattern
      with squares and rectangles of different dimensions and chemistry. The
      microstructured surfaces were characterized by scanning electron microscopy (SEM)
      and atomic force microscopy (AFM). The behavior of human coronary artery
      endothelial cells (HCAEC) and human tumoral dermal fibroblasts (C54) was
      investigated on these micropatterned surfaces by adhesion studies. Moreover
      heterotypic interaction among C54 and HCAEC adherent on patterned surfaces was
      evaluated by time-lapse video microscopy RESULTS: Surface analysis revealed the
      presence of a pattern consisting of alternating glass and Hyal microstructures
      whose dimensions decreased from the center to the edge of the sample. Neither
      HCAEC nor C54 adhered to the immobilized Hyal but both adapted their shape to the
      different sizes of the glass squares and rectangles. The number of adherent cells
      depended on the dimensions of both the glass domains and the nuclei of the cells.
      Co-cultured C54 on HCAEC patterned surfaces showed a heterotypic cell-cell
      interaction in the same chemical and topographic domain. CONCLUSIONS: A
      heterotypic cell-cell interaction occurred in the same chemical and topographic
      micro-domains but in narrow areas only. Moreover, the number of cells adhering to
      the glass domains and cell morphology depended on the dimensions of both adhesive
      areas and cell nuclei.

PMID- 19844890
TI  - Health-related quality of life in dialysis patients with HCV infection.
AB  - Measuring the impact of chronic kidney disease (CKD) treatment on patient quality
      of life has become increasingly recognized as an important outcome measure.
      Despite improvements in the treatment of chronic kidney disease, health-related
      quality of life (HRQOL) is lower than in the general population. HRQOL measures,
      particularly the Physical Component Summary (PCS), have predictive validity for
      risk of both mortality and hospitalization in dialysis populations. For every 10
      point lower PCS score, the relative risk (RR) of death increases by 29% (RR =
      1.29; 95% CI = 1.23 to 1.35; p < 0.001) and the risk of hospitalization increases
      by 15% (RR = 1.15; 95% CI = 1.11 to 1.19, p < 0.001), according to the Dialysis
      Outcomes and Practice Patterns Study (DOPPS). Hepatitis C virus (HCV) infection
      remains prevalent among dialysis patients with a recent meta-analysis showing
      that anti-HCV seropositive status was an independent and significant risk factor
      for death in patients on maintenance dialysis. Seven studies with 11,589 unique
      patients on maintenance dialysis were identified; the summary estimate for
      adjusted relative risk (aRR) (all-cause mortality) was 1.34 with a 95% confidence
      interval (CI) of 1.13-1.59. In non-uremic populations HCV diminishes HRQOL, and
      individuals with HCV scored lower than controls across all scales of the short
      form 36 (SF-36). Patients achieving sustained virological responses (SVR) scored
      higher across all scales versus patients without SVR, especially in the physical
      health domains. Whether the adverse influence of HCV on survival in dialysis
      population is related to the negative impact of HCV on HRQOL requires further
      research. Information on HRQOL indices in patients with HCV on maintenance
      dialysis is extremely limited but the available evidence shows that HCV infection
      impairs HRQOL, especially in mental aspects, among patients on maintenance
      hemodialysis.

PMID- 19844891
TI  - Ovine models for chronic heart failure.
AB  - PURPOSE: Testing and optimizing of surgical therapies for chronic heart failure
      (CHF) requires large animal models. CHF has been induced in several large animal
      species. Sheep have modest body mass increase and demonstrate docile behavior and
      are therefore a preferred species in research on surgical therapies for CHF
      METHODS: A literature search for existing ovine CHF models was performed, using
      search terms "sheep" and "heart failure". Relevant secondary references were
      traced. RESULTS: Rapid ventricular pacing produces rapid-onset CHFE Its severity
      ranges from moderate left ventricular failure to severe biventricular failure,
      depending on length and frequency of pacing. Its counterpart in human CHF is
      tachycardia-induced HF since it is reversible upon cessation of pacing.
      Myocardial damage models include CHF induced by cardiototoxic drugs and ischemia.
      Ischemia-based models include coronary microembolization, occlusion and
      ischemia/reperfusion models. The microembolization model is relevant to diabetic
      cardiomyopathy. Coronary occlusion models exhibit variable functional impairment,
      some with aneurysm formation, and some with mitral valve regurgitation, depending
      on occlusion localization. They are relevant to CHF following non-reperfused
      myocardial infarction. Coronary occlusion/reperfusion models are relevant to the
      occurrence of human aa despite coronary artery recanalization. Pressure overload
      of left and right ventricle is induced by aortic and pulmonary artery banding,
      respectively. Hypertrophy precedes CHF as in patients with valve stenosis and
      hypertension. Volume overload is induced by valve damage or shunt creation.
      Atrioventricular valve regurgitation is the most important clinical counterpart.
      CONCLUSION: Several ovine CHF models exist. Since they exhibit important cardiac
      pathology differences, the choice of model should be based on the specific
      experimental question.

PMID- 19844892
TI  - In vitro tests and modelization of bicarbonate kinetics and mass transfers during
      online hemodiafiltration.
AB  - This paper proposes an in vitro hemodiafiltration (HDF) model in which the
      patient is represented by a 2 L bag of fresh heparinized bovine blood circulated
      by a 4008H monitor through a 0.6 m2 hemodialyzer to investigate kinetics of
      bicarbonate (HCO,) during online post-dilution HDF. Five tests were carried out,
      with three ultrafiltration rates, zero (HD test), 30 and 50 ml/min. Blood gases,
      pH, HCO3, hematocrit and electrolytes were measured with an ABL 77 (Radiometer)
      blood gas analyzer, and HCO3- was simultaneously measured with a biochemistry
      analyzer. The variation over time of plasma HCO3- concentrations was also
      calculated using mass conservation and the model of Legallais et al (JMS 168,
      2000, 3-15). Agreement between theoretical and measured concentrations was good
      during the first 25 minutes of each test, corresponding to the time necessary to
      dialyze the blood. In hemodialysis (HD), there was an HCO3- mass transfer into
      blood through the membrane due to diffusion which vanished after 40 minutes,
      while in HDF tests, blood lost HCO3 due to ultrafiltration after 10 minutes. With
      reinjection, the net HCO3- mass flow rate to the "patient" decayed, from 1.8
      mmol/min at t = 0 to zero at the end of the test (t = 60 min), and was higher in
      HD than in HDF "Patient" dialysance, taking into account reinjection, was
      positive in all tests, and decayed from about 110 ml/ min to 40 m/min at the end
      of dialysis. These data confirmed that online HDF automatically corrects acidosis
      without creating alkalosis when HCO3- dialysate concentration is around 30
      mmol/L.

PMID- 19844893
TI  - Dialysis initiation and survival in patients with refractory congestive heart
      failure.
AB  - BACKGROUND: It has been reported that more than 30% of patients present with
      congestive heart failure at the initiation of renal replacement therapy (RRT). We
      followed up a cohort of patients with refractory congestive heart failure (RCHF)
      who started dialysis between 2005 and 2006 and conducted an observational cohort
      study in order to evaluate the clinical features at the time RRT was started, and
      the survival rate of patients with RCHF METHODS: Data were collected on 33 uremic
      subjects (24 male) with RCHF, referred by cardiologists, who started dialysis
      between 2005 and 2006 and were followed-up for 42 months. The following
      parameters were derived from clinical records: age, sex, history of ischemic
      heart disease (IHD), cerebrovascular disease (CVD), peripheral vascular disease
      (PVD), diabetes, smoking, hypertension, myeloma or malignancies, the cause for
      dialysis and procedure used to initiate treatment. RESULTS: RCHF was the cause of
      initial RRT in 15 patients in 2005 and in 18 the following year with an incidence
      of 27 out of 100 patients per year. Diabetes was diagnosed in 51% (n = 17) of
      cases. More than 80% of patients with RCHF had histories of hypertension and
      smoking. IHD, CVD and PVD were present in 66%, 30% and 54% of cases,
      respectively. Cancers were recorded in 36% of subjects. Fluid overload was the
      cause of urgent dialysis in 73% of cases; a central venous catheter (CVC) was
      placed in 75% of patients. Mean survival of patients with RCHF was 23 months.
      Eighteen patients died because of cardiovascular events after a mean follow-up of
      365 +/- 387 days; they had higher prevalence of a smoking history (100% vs. 73%,
      p = 0.02) and CVD (44% vs. 13%, p = 0.05) than the survivors. CONCLUSIONS: In
      uremic patients starting dialysis, RCHF appears to be a frequent condition,
      comorbidity is high and they require urgent treatment by CVC because of fluid
      overload. Since RCHF is time- and resource-consuming, nephrologists need to
      ameliorate its management.

PMID- 19844894
TI  - Functional evaluation of the endotics system, a new disposable self-propelled
      robotic colonoscope: in vitro tests and clinical trial.
AB  - OBJECTIVE: Currently, the best method for CRC screening is colonoscopy, which
      ideally (where possible) is performed under partial or deep sedation. This study
      aims to evaluate the efficacy of the Endotics System, a new robotic device
      composed of a workstation and a disposable probe, in performing accurate and well
      tolerated colonoscopies. This new system could also be considered a precursor of
      other innovating vectors for atraumatic locomotion through natural orifices such
      as the bowel. The flexible probe adapts its shape to the complex contours of the
      colon, thereby exerting low strenuous forces during its movement. These novel
      characteristics allow for a painless and safe colonoscopy, thus eliminating all
      major associated risks such as infection, cardiopulmonary complications and colon
      perforation. METHODS: An experimental study was devised to investigate stress
      pattern differences between traditional and robotic colonoscopy, in which 40
      enrolled patients underwent both robotic and standard colonoscopy within the same
      day. RESULTS: The stress pattern related to robotic colonoscopy was 90% lower
      than that of standard colonoscopy. Additionally, the robotic colonoscopy
      demonstrated a higher diagnostic accuracy, since, due to the lower insufflation
      rate, it was able to visualize small polyps and angiodysplasias not seen during
      the standard colonoscopy. All patients rated the robotic colonoscopy as virtually
      painless compared to the standard colonoscopy, ranking pain and discomfort as 0.9
      and 1.1 respectively, on a scale of O to 10, versus 6.9 and 6.8 respectively for
      the standard device. CONCLUSIONS: The new Endotics System demonstrates efficacy
      in the diagnosis of colonic pathologies using a procedure nearly completely
      devoid of pain. Therefore, this system can also be looked upon as the first step
      toward developing and implementing colonoscopy with atraumatic locomotion through
      the bowel while maintaining a high level of diagnostic accuracy;

PMID- 19844895
TI  - Synaptic organization in the adult Drosophila mushroom body calyx.
AB  - Insect mushroom bodies are critical for olfactory associative learning. We have
      carried out an extensive quantitative description of the synaptic organization of
      the calyx of adult Drosophila melanogaster, the main olfactory input region of
      the mushroom body. By using high-resolution confocal microscopy, electron
      microscopy-based three-dimensional reconstructions, and genetic labeling of the
      neuronal populations contributing to the calyx, we resolved the precise
      connections between large cholinergic boutons of antennal lobe projection neurons
      and the dendrites of Kenyon cells, the mushroom body intrinsic neurons.
      Throughout the calyx, these elements constitute synaptic complexes called
      microglomeruli. By single-cell labeling, we show that each Kenyon cell's claw
      like dendritic specialization is highly enriched in filamentous actin, suggesting
      that this might be a site of plastic reorganization. In fact, Lim kinase (LimK)
      overexpression in the Kenyon cells modifies the shape of the microglomeruli.
      Confocal and electron microscopy indicate that each Kenyon cell claw enwraps a
      single bouton of a projection neuron. Each bouton is contacted by a number of
      such claw-like specializations as well as profiles of gamma-aminobutyric acid
      positive neurons. The dendrites of distinct populations of Kenyon cells involved
      in different types of memory are partially segregated within the calyx and
      contribute to different subsets of microglomeruli. Our analysis suggests, though,
      that projection neuron boutons can contact more than one type of Kenyon cell.
      These findings represent an important basis for the functional analysis of the
      olfactory pathway, including the formation of associative olfactory memories.

PMID- 19844896
TI  - The reproducibility of ethnic differences in the proportional awake-sleep blood
      pressure decline among women.
AB  - A growing body of evidence indicates that African Americans (AA), on average,
      have a smaller proportional decline in blood pressure (BP) from waking to sleep
      than European Americans (EA), but this difference is largely based on
      correlational data from a single assessment day. The persistence of this
      difference over repeated sampling is not well established. The purpose of this
      study was to evaluate whether ethnic differences in the awake-sleep BP decline
      between AA and EA persisted over three monthly assessments. The subjects were 47
      AA (age = 39.7 +/- 8.7) and 92 EA (age = 37.4 +/- 9.2) normotensive women.
      Subjects had 24-h ambulatory BP monitoring done on midweek workdays at 1-month
      intervals for three consecutive months. The proportional decline in BP was
      calculated as follows: (average awake - average sleep)/average sleep. The
      persistence of ethnic differences was evaluated using repeated-measures ANCOVA
      and by examining Bland-Altman plots. The ANCOVA results revealed that overall,
      the proportional decline of AA women was less than that of EA women for both SBP
      (P < 0.038) and DBP (P < 0.083), consistent with previous research, and that
      there were also no significant ethnic differences by monthly assessment. Bland
      Altman plots revealed that overall and by ethnicity, the proportional decline in
      BP among individual subjects over the 3 months was also reproducible. These
      results suggest that the ethnic difference in awake-sleep BP between AA and EA
      women persists over time and that the awake-sleep decline in BP among
      individuals, whether AA or EA, is also reproducible.

PMID- 19844897
TI  - Maternal capital and the metabolic ghetto: An evolutionary perspective on the
      transgenerational basis of health inequalities.
AB  - There is particular interest in understanding socioeconomic and ethnic
      variability in health status. The developmental origins of disease hypothesis
      emphasize the importance of growth patterns across the life-course in relation to
      noncommunicable disease risk. The physiological components of cardiovascular
      risk, collectively termed the metabolic syndrome, derive in part from a disparity
      between the homeostatic "metabolic capacity" of vital organs and the "metabolic
      load" induced by large tissue masses, a rich diet and sedentary behavior. From an
      evolutionary perspective, the risk of such disparity is decreased by maternal
      physiology regulating offspring growth trajectory during gestation and lactation.
      Maternal capital, defined as phenotypic resources enabling investment in the
      offspring, allows effective buffering of the offspring from nutritional
      perturbations and represents the environmental niche initially occupied by the
      offspring. Offspring growth patterns are sensitive to the magnitude of maternal
      capital during early windows of plasticity. Offspring life-history strategy can
      then respond adaptively to further factors across the life-course, but only
      within the context of this initial maternal influence on growth. Maternal somatic
      capital is primarily gained or lost across generations, through variable rates of
      fetal and infant growth. I argue that the poor nutritional experience of
      populations subjected to colonialism resulted in a systematic loss of maternal
      capital, reflected in downward secular trends in stature. Accelerating the
      recovery of somatic capital within generations overloads metabolic capacity and
      exacerbates cardiovascular risk, reflected in increased disease rates in
      urbanizing and emigrant populations. Public health policies need to benefit
      metabolic capacity without exacerbating metabolic load.

PMID- 19844898
TI  - Boys live dangerously in the womb.
AB  - The growth of every human fetus is constrained by the limited capacity of the
      mother and placenta to deliver nutrients to it. At birth, boys tend to be longer
      than girls at any placental weight. Boy's placentas may therefore be more
      efficient than girls, but may have less reserve capacity. In the womb boys grow
      faster than girls and are therefore at greater risk of becoming undernourished.
      Fetal undernutrition leads to small size at birth and cardiovascular disorders,
      including hypertension, in later life. We studied 2003 men and women aged around
      62 years who were born in Helsinki, Finland, of whom 644 had hypertension: we
      examined their body and placental size at birth. In both sexes, hypertension was
      associated with low birth weight. In men, hypertension was also associated with a
      long minor diameter of the placental surface. The dangerous growth strategy of
      boys may be compounded by the costs of compensatory placental enlargement in late
      gestation. In women, hypertension was associated with a small placental area,
      which may reduce nutrient delivery to the fetus. In men, hypertension was linked
      to the mothers' socioeconomic status, an indicator of their diets: in women it
      was linked to the mothers' heights, an indicator of their protein metabolism.
      Boys' greater dependence on their mothers' diets may enable them to capitalize on
      an improving food supply, but it makes them vulnerable to food shortages. The
      ultimate manifestation of their dangerous strategies may be that men have higher
      blood pressures and shorter lives than women.

PMID- 19844899
TI  - Short but catching up: statural growth among native Amazonian Bolivian children.
AB  - The ubiquity and consequences of childhood growth stunting (<-2 SD in height-for
      age Z score, HAZ) in rural areas of low-income nations has galvanized research
      into the reversibility of stunting, but the shortage of panel data has hindered
      progress. Using panel data from a native Amazonian society of foragers-farmers in
      Bolivia (Tsimane'), we estimate rates of catch-up growth for stunted children.
      One hundred forty-six girls and 158 boys 2 < or = age < or = 7 were measured
      annually during 2002-2006. Annual Delta height in cm and in HAZ were regressed
      separately against baseline stunting and control variables related to attributes
      of the child, mother, household, and village. Children stunted at baseline had
      catch-up growth rates 0.11 SD/year higher than their nonstunted age and sex
      peers, with a higher rate among children farther from towns. The rate of catch up
      did not differ by the child's sex. A 10% rise in household income and an
      additional younger sibling lowered by 0.16 SD/year and 0.53 SD/year the rate of
      growth. Results were weaker when measuring Delta height in cm rather than in HAZ.
      Possible reasons for catch-up growth include (a) omitted variable bias, (b)
      parental reallocation of resources to redress growth faltering, particularly if
      parents perceive the benefits of redressing growth faltering for child school
      achievement, and (c) developmental plasticity during this period when growth
      rates are most rapid and linear growth trajectories have not yet canalized.

PMID- 19844900
TI  - Human birth seasonality and sunshine.
AB  - The environmental light intensity/photoperiod (ELI/PP) hypothesis proposes that
      the seasonality of human births is primarily associated with seasonal changes in
      ambient atmospheric luminosity or ELI. This study tests for the presence of
      increased ELI during the 1 or 2-month period preceding the conceptual month.
      Monthly birth data for Helsinki, Finland; Kiev, Ukraine; Hanoi, Vietnam; Matlab,
      Bangladesh; Nashville, Tennessee; Los Angeles, California; Dallas, Texas; Denver,
      Colorado and Pretoria, South Africa, are correlated (Pearsonian r) to
      corresponding monthly meteorological data. With the exception of Matlab, birth
      data are adjusted for conception date, 31-day months, leap years and monthly
      deviation from an annual mean. Meteorological data are adjusted for a 1-2-month
      exposure to ELI before conception. From these correlations, Helsinki r = 0.82,
      Kiev r = 0.80, Hanoi r = 0.93, Matlab r = 0.91, Nashville r = 0.84, Los Angeles r
      = 0.71, Dallas r = 0.86, Denver r = 0.53, and Pretoria r = -82. Weakness and
      strengths of the ELI/PP hypothesis are reviewed using the criteria developed by
      AB Hill. Substituting meteorological variables for ELI may be a weakness, whereas
      the specificity of ELI/PP predictions may be a strength. Increased periods of ELI
      precede increased periods of conceptions. Increased ELI may influence seasonality
      for chimpanzee, baboon, and humans. Atmospheric pollution may alter the onset of
      seasonality. Increased ELI may be the initial, but not the singular variable to
      affect seasonality.

PMID- 19844901
TI  - Stability of genetic influences on pulmonary function in a longitudinal study of
      octogenarian twins.
AB  - Using data from the first four waves of the OCTO-Twin study (twins 80 + years),
      the present study investigated the stability and change of genetic and
      environmental contributions to pulmonary function. Using a genetic simplex model,
      variance in peak expiratory flow (PEF) at each wave was decomposed into additive
      genetic and nonshared (specific) environmental factors. Additionally, this
      analysis distinguished the source of these influences, either from previous waves
      (transmissions) or from novel influences at each wave (innovations). At each time
      point (except wave 1), the genetic variance was due to genetic transmissions from
      prior time points. Conversely, the specific environmental variance in PEF at each
      time point was mainly due to environmental innovations. These results imply that
      genetic factors contribute to the stability of pulmonary function over time
      whereas environmental factors contribute to its change.

PMID- 19844902
TI  - Does second-to-fourth digit length ratio (2D:4D) predict age at menarche in
      women?
AB  - Prenatal steroid levels, estimated as the ratio of second-to-fourth digit length
      (2D:4D), have been related to reproductive success in women, but direct
      associations between 2D:4D and physiological measures of fertility remain rare. A
      recent study reported that lower, masculinized right hand 2D:4D was correlated
      with delayed age at menarche in women. We addressed this question by
      investigating whether 2D:4D was associated with recalled age at menarche in 282
      post-reproductive Finnish women, using Cox regression model that controlled for a
      woman's sibling composition, urban or rural residence and temporal trend in
      menarcheal age. We found no evidence that neither the 2D:4D of the right nor the
      left hand were related to a woman's age at menarche among these Finnish women.

PMID- 19844903
TI  - Childhood conditions and education as determinants of adult height and obesity
      among Greenland Inuit.
AB  - Height and obesity are risk factors for cardiovascular disease and other physical
      and mental health conditions. Their association with childhood socioeconomic
      position has been demonstrated in studies among European and a few third world
      populations. In a random sample of adult Greenland Inuit (N = 2302) we studied
      the association between childhood socioeconomic conditions and height as well as
      prevalence of obesity (BMI > or = 30) in a cross sectional design. In block
      recursive graphical independence models, height was associated with mother's
      place of birth, birth cohort, childhood residence, alcohol problems in childhood
      home, and education among both men and women. Obesity was associated with
      mother's place of birth (for men) and with alcohol problems (for women). In
      General Linear Models, men with an all rural background and no education beyond
      primary school measured on average 165.1 cm compared with 172.1 cm for men with
      an all urban background (P < 0.001); women measured 153.9 and 161.1 cm (P <
      0.001). Rural-urban differences in prevalence of obesity were not statistically
      significant. The height differences were considerably larger than between
      educational groups in European countries and of the same order of magnitude as
      those reported between men from the 17th century and men from 400 BC in the
      European and Mediterranean region. The rural-urban gradient in height follows the
      socioeconomic gradient and may negatively affect cardiovascular risk among the
      rural Greenlanders, while their physically active lifestyle and high consumption
      of n-3 fatty acids may counteract this.

PMID- 19844904
TI  - Discrimination, psychosocial stress, and health among Latin American immigrants
      in Oregon.
AB  - Chronic psychosocial stress related to discrimination has been shown to be
      associated with biological measures such as elevated systolic blood pressure
      (SBP), increased body fat, and higher fasting glucose levels. Few studies have
      examined these relationships in immigrant populations. The present study
      recruited a sample of 132 Oregon Latino immigrant adults to investigate the
      relationships between perceived discrimination and several health measures (blood
      pressure, body mass index [BMI], and fasting glucose). Results indicate that
      perceived discrimination stress predicted elevated SBP among men but not among
      women. Perceived discrimination was significantly higher among obese women than
      among women of normal BMI. The same pattern was not observed for men. Further, a
      strong trend relationship was detected: the higher women's reported
      discrimination stress, the higher their fasting glucose levels. Again, this
      pattern was not observed for men. These results suggest that chronic psychosocial
      stress plays an important role in disease risk among Latin American immigrants,
      and that male and female immigrants may have distinctive physiological responses.
      If confirmed, these findings may have important clinical and public health
      implications for chronic disease prevention among Latinos.

PMID- 19844908
TI  - Effect of surface properties on nanoparticle-cell interactions.
AB  - The interaction of nanomaterials with cells and lipid bilayers is critical in
      many applications such as phototherapy, imaging, and drug/gene delivery. These
      applications require a firm control over nanoparticle-cell interactions, which
      are mainly dictated by surface properties of nanoparticles. This critical Review
      presents an understanding of how synthetic and natural chemical moieties on the
      nanoparticle surface (in addition to nanoparticle shape and size) impact their
      interaction with lipid bilayers and cells. Challenges for undertaking a
      systematic study to elucidate nanoparticle-cell interactions are also discussed.

PMID- 19844910
TI  - Gene expression changes in blood as a putative biomarker for Huntington's
      disease.
AB  - Several studies demonstrated alterations of gene expression in blood in various
      neurological disorders including Huntington's disease (HD). Using microarray
      technology, a recent study identified a large number of significantly altered
      mRNAs in HD blood, from which a 12-gene set was selected as classifier for
      discriminating controls and HD patients. The aim of our study was to validate
      expression changes of these 12 genes in an independent cohort of HD patients and
      evaluate their sensitivity and specificity. Four different subject groups were
      included--patients with HD, Parkinson's disease (PD), acute ischemic stroke (AS)
      and healthy controls. Although the previous results were successfully validated,
      gene expression changes in HD blood partly overlapped with those observed in
      blood from PD and AS patients. Predictive value of the selected biomarker set for
      HD group was 78%, with 82% sensitivity and 53% specificity. Further gene
      expression analyses in longitudinal studies are needed to validate and refine
      possible transcriptomic blood biomarkers in HD.

PMID- 19844911
TI  - A food safety control low mass-range proteomics platform for the detection of
      illicit treatments in veal calves by MALDI-TOF-MS serum profiling.
AB  - Performance enhancing agents (PEAs) are illegally used in cattle and other meat
      producing species to increase food conversion and lean meat production. Due to
      the very short breeding cycle, veal calves represent the meat producing bovine
      category mostly subjected to illicit treatments. These chemical agents are
      difficult to detect by conventional analytical approaches due to the employment
      of synergistic formulations at very low dosage and given the use of
      uncharacterized novel compounds. Such a scenario has fostered a strong interest
      in the discovery of functional molecular biomarkers for the detection of growth
      promoting agents in meat producing species. A multivariate MALDI-TOF-MS
      proteomics platform has been developed using bovine serum samples. Analytical
      performances have been thoroughly evaluated in order to enable reproducible
      profiles from 10 microL sera samples. We propose univariate and multivariate
      discrimination models capable to identify calves undergoing illicit treatments.
      In particular, we found a strong discrimination power associated with a
      polypeptide fragment from beta2-glycoprotein-I. We provide a fundamental proof of
      concept in the potential application of MALDI-TOF-MS proteomics profiling in the
      food safety control.

PMID- 19844912
TI  - Barley as a green factory for the production of functional Flt3 ligand.
AB  - Biologically active recombinant human Flt3 ligand was expressed and isolated from
      transgenic barley seeds. Its expression is controlled by a tissue specific
      promoter that confines accumulation of the recombinant protein to the endosperm
      tissue of the seed. The recombinant Flt3 ligand variant expressed in the seeds
      contains an HQ-tag for affinity purification on immobilized metal ion affinity
      chromatography (IMAC) resin. The tagged protein was purified from seed extracts
      to near homogeneity using sequential chromatography on IMAC affinity resin and
      cation exchange resin. We also show that the recombinant Flt3 ligand protein
      undergoes posttranslational modifications: it is a glycoprotein containing alpha
      1,3-fucose and alpha-1,2-xylose. The HQ-tagged Flt3 ligand variant exhibits
      comparable biological activity to commercial Flt3 ligand. This is the first
      report showing expression and accumulation of recombinant human growth factor in
      barley seeds with a yield of active protein similar to a bacterial expression
      system. The present results demonstrate that plant molecular farming is a viable
      approach for the bioproduction of human-derived growth factors.

PMID- 19844913
TI  - Insect-symbiont systems: from complex relationships to biotechnological
      applications.
AB  - Microbial symbiosis is a ubiquitous aspect of life and was a major element in the
      ability of insects to explore several adverse environments. To date, the study of
      symbiosis in insects has been impaired by the unculturability of most symbionts.
      However, some molecular methods represent powerful tools to help understand
      insect-microorganism associations and to disclose new symbiont-host systems.
      Beyond playing an essential role in nutrition and development of the insects,
      symbionts can produce bioactive compounds that protect the host against adverse
      environmental conditions, predators and/or direct competitors. Since the search
      for natural bioactive products and new enzymes is a developing area,
      understanding the diversity and nature of symbiont-host relationships paves the
      way for the exploitation of new resources in biotechnology. Furthermore, genetic
      transformation of the symbionts with genes that code for compounds that are toxic
      for pathogenic and phytopathogenic agents is also a promising area of application
      of the insect-symbiont relationships. The search for new bioactive compounds, the
      use of symbionts for pest and disease control and the molecular strategies
      applied for these purposes are issues of particular interest for innovative
      biotechnological applications and are addressed in the present review.

PMID- 19844914
TI  - An integrated microdevice for high-performance short tandem repeat genotyping.
AB  - Short tandem repeat (STR) analysis provides genetic fingerprinting of
      individuals, and is considered as a powerful and indispensable technique for
      forensic human identification. However, the current state-of-the-art STR
      genotyping processes and instruments are labor intensive, expensive, time
      consuming, and lack portability. Micro-total-analysis systems or lab-on-a-chip
      platforms based on microfabrication technologies have the capability to
      miniaturize and integrate bioanalysis steps in a single format. Recent progress
      in microsystems has demonstrated their successful performance for the forensic
      STR typing with a reduced cost, high speed, and improved high throughput. The
      purpose of this review article is to highlight up-to-date work on advanced
      microdevices for high-throughput STR genotyping, and a portable integrated
      microsystem for on-site forensic DNA analysis.

PMID- 19844915
TI  - Industrial biotechnology: tools and applications.
AB  - Industrial biotechnology involves the use of enzymes and microorganisms to
      produce value-added chemicals from renewable sources. Because of its association
      with reduced energy consumption, greenhouse gas emissions, and waste generation,
      industrial biotechnology is a rapidly growing field. Here we highlight a variety
      of important tools for industrial biotechnology, including protein engineering,
      metabolic engineering, synthetic biology, systems biology, and downstream
      processing. In addition, we show how these tools have been successfully applied
      in several case studies, including the production of 1, 3-propanediol, lactic
      acid, and biofuels. It is expected that industrial biotechnology will be
      increasingly adopted by chemical, pharmaceutical, food, and agricultural
      industries.

PMID- 19844916
TI  - Biosynthesis of Sb2O3 nanoparticles: a low-cost green approach.
AB  - A low-cost green and reproducible microbe (Lactobacillus sp.)-mediated
      biosynthesis of Sb(2)O(3) nanoparticles is reported. The synthesis was performed
      at around room temperature. X-ray and transmission electron microscopy analyses
      were performed to ascertain the formation of Sb(2)O(3) nanoparticles. X-ray
      analysis indicated that Sb(2)O(3) nanoparticles had a face-centered cubic unit
      cell structure. Individual nanoparticles as well as a few aggregates of 3-12 nm
      were found. A possible mechanism for the synthesis of nano Sb(2)O(3) is proposed.

PMID- 19844917
TI  - Statistical aspects of design and validation of microtitre-plate-based linear and
      non-linear parallel in vitro bioassays.
AB  - Assay validation was performed using four consecutive experiments with the
      related statistical evaluation. A cell-based assay on microtitre plates measured
      repeatedly within 1 day and on consecutive days was chosen as the model. The
      following problems were addressed: (i) choosing an appropriate design on a plate
      to avoid heterogeneities, (ii) quantification of all sources of variability and
      (iii) selecting between linear and non-linear parallel line assays. A mixed model
      was used with the random factors: rows, columns and plates and fixed effect
      factors with either linear or non-linear parallel line models.

PMID- 19844918
TI  - Recent trends in non-viral vector-mediated gene delivery.
AB  - Nucleic acids-based next generation biopharmaceuticals (i.e., pDNA,
      oligonucleotides, short interfering RNA) are potential pioneering materials to
      cope with various incurable diseases. However, several biological barriers
      present a challenge for efficient gene delivery. On the other hand, developments
      in nanotechnology now offer numerous non-viral vectors that have been fabricated
      and found capable of transmitting the biopharmaceuticals into the cell and even
      into specific subcellular compartments like mitochondria. This overview
      illustrates cellular barriers and current status of non-viral gene vectors, i.e.,
      lipoplexes, liposomes, polyplexes, and nanoparticles, to relocate therapeutic DNA
      based nanomedicine into the target cell. Despite the awesome impact of physical
      methods (i.e., ultrasound, electroporation), chemical methods have been shown to
      accomplish high-level and safe transgene expression. Further comprehension of
      barriers and the mechanism of cellular uptake will facilitate development of
      nucleic acids-based nanotherapy for alleviation of various disorders.

PMID- 19844919
TI  - Chemical strategies for immobilization of oligonucleotides.
AB  - The development of oligonucleotide-based microarrays (biochips) is a major thrust
      area in the rapidly growing biotechnology industry, which encompasses a diverse
      range of research areas including genomics, proteomics, computational biology,
      and pharmaceuticals, among other activities. Microarray experiments have proved
      to be unique in offering cost-effective and efficient analysis at the genomic
      level. In the last few years, biochips have gained increasing acceptance in the
      study of genetic and cellular processes. As the increase in experimental
      throughput has posed many challenges to the research community, considerable
      progress has been made in the advancement of microarray technology. In this
      review, chemical strategies for immobilization of oligonucleotides have been
      highlighted with special emphasis on post-synthetic immobilization of
      oligonucleotides on glass surface. The major objective of this article is to make
      the researchers acquainted with some most recent advances in this area.

PMID- 19844920
TI  - Eating dystonia.

PMID- 19844922
TI  - Seladin-1 and testicular germ cell tumours: new insights into cisplatin
      responsiveness.
AB  - The molecular basis for the exquisite sensitivity of testicular germ cell tumours
      of adolescents and adults (TGCTs), ie seminomas and non-seminomatous germ cell
      tumours, to chemo/radiotherapy has not been fully clarified so far. It has been
      suggested that it may be dependent on factors involved in the regulation of
      apoptosis. Seladin-1 is a multi-functional protein involved in various biological
      processes, including apoptosis. The aim of our study was to assess the expression
      of seladin-1 in different histological types of TGCTs, known to have varying
      treatment sensitivity, in order to establish whether this protein may influence
      cisplatin responsiveness in vitro. Seladin-1 expression levels, both at the mRNA
      and at the protein level, were higher in the adjacent normal parenchyma than in
      the pathological counterparts. In tumoural tissues, the level of expression
      differed among TGCT histological types. The highest tumour-expression level was
      found in teratoma, whereas the lowest was detected in seminoma, corresponding to
      the different chemo/and radiosensitivities of these tumour types. In common with
      other cancers, in TGCT-derived cell lines seladin-1 showed anti-apoptotic
      properties through inhibition of caspase-3 activation. We confirmed our results
      using a non-seminomatous cell line model (NT2) before and after differentiation
      with retinoic acid. Significantly higher seladin-1 expression was observed in the
      differentiated derivatives (teratoma) and an inverse relationship was found
      between seladin-1 expression and the amount of cleaved caspase-3. Seladin-1
      silencing or overexpression in this cell line supports involvement of seladin-1
      in cisplatin responsiveness. Seladin-1 silencing was associated with greater
      cisplatin responsiveness demonstrated by decreased cell viability and increased
      expression of apoptotic markers. In contrast, overexpression of seladin-1 was
      associated with a higher survival rate and a clear anti-apoptotic effect. In
      conclusion, we have demonstrated for the first time an important role for seladin
      1 in the biology of TGCTs and provided new insights into cisplatin responsiveness
      of these tumours.

PMID- 19844923
TI  - Understanding, controlling and programming cooperativity in self-assembled
      polynuclear complexes in solution.
AB  - Deviations from statistical binding, that is cooperativity, in self-assembled
      polynuclear complexes partly result from intermetallic interactions DeltaE(M,M),
      whose magnitudes in solution depend on a balance between electrostatic repulsion
      and solvation energies. These two factors have been reconciled in a simple point
      charge model, which suggests severe and counter-intuitive deviations from
      predictions based solely on the Coulomb law when considering the variation of
      DeltaE(M,M) with metallic charge and intermetallic separation in linear
      polynuclear helicates. To demonstrate this intriguing behaviour, the ten
      microscopic interactions that define the thermodynamic formation constants of
      some twenty-nine homometallic and heterometallic polynuclear triple-stranded
      helicates obtained from the coordination of the segmental ligands L1-L11 with
      Zn(2+) (a spherical d-block cation) and Lu(3+) (a spherical 4f-block cation),
      have been extracted by using the site binding model. As predicted, but in
      contrast with the simplistic coulombic approach, the apparent intramolecular
      intermetallic interactions in solution are found to be i) more repulsive at long
      distance (DeltaE(1-4)(Lu,Lu)>DeltaE(1-2)(Lu,Lu)), ii) of larger magnitude when
      Zn2+ replaces Lu3+ (DeltaE(1-2)(Zn,Lu)>DeltaE(1-2)(Lu,Lu) and iii) attractive
      between two triply charged cations held at some specific distance (DeltaE(1
      3)(Lu,Lu)<0). The consequences of these trends are discussed for the design of
      polynuclear complexes in solution.

PMID- 19844921
TI  - Broadening the mission of an RNA enzyme.
AB  - The "RNA World" hypothesis suggests that life developed from RNA enzymes termed
      ribozymes, which carry out reactions without assistance from proteins.
      Ribonuclease (RNase) P is one ribozyme that appears to have adapted these origins
      to modern cellular life by adding protein to the RNA core in order to broaden the
      potential functions. This RNA-protein complex plays diverse roles in processing
      RNA, but its best-understood reaction is pre-tRNA maturation, resulting in mature
      5' ends of tRNAs. The core catalytic activity resides in the RNA subunit of
      almost all RNase P enzymes but broader substrate tolerance is required for
      recognizing not only the diverse sequences of tRNAs, but also additional cellular
      RNA substrates. This broader substrate tolerance is provided by the addition of
      protein to the RNA core and allows RNase P to selectively recognize different
      RNAs, and possibly ribonucleoprotein (RNP) substrates. Thus, increased protein
      content correlated with evolution from bacteria to eukaryotes has further
      enhanced substrate potential enabling the enzyme to function in a complex
      cellular environment.

PMID- 19844924
TI  - Oligothiophenes nano-organized on a cyclotetrasiloxane scaffold as a model of a
      silica-bound monolayer: evidence for intramolecular excimer formation.
AB  - Excimer formation in a new class of terthiophene-based fluorophores covalently
      bonded to a cyclotetrasiloxane scaffold has been demonstrated and the
      photophysical process ruling it has been investigated in detail and modeled
      theoretically. In contrast to the conventional systems in which long-living
      fluorophores such as pyrene are linked in the same molecule, an excimer is formed
      only when two terthiophene-based branches nano-organized on the same
      cyclotetrasiloxane scaffold are close enough together when excitation takes
      place. In such a case, excimer formation is extremely efficient, and the new
      bound excited states are quite stable.

PMID- 19844925
TI  - When VSEPR fails: experimental and theoretical investigations of the behavior of
      alkaline-earth-metal acetylides.
AB  - The synthesis, structural, and spectral characterization as well as a theoretical
      study of a family of alkaline-earth-metal acetylides provides insights into
      synthetic access and the structural and bonding characteristics of this group of
      highly reactive compounds. Based on our earlier communication that reported
      unusual geometry for a family of triphenylsilyl-substituted alkaline-earth-metal
      acetylides, we herein present our studies on an expanded family of target
      derivatives, providing experimental and theoretical data to offer new insights
      into the intensively debated theme of structural chemistry in heavy alkaline
      earth-metal chemistry.

PMID- 19844926
TI  - Geminal ionic liquids: a combined approach to investigate their three-dimensional
      organisation.
AB  - Different investigations, such as 1D and 2D NMR spectroscopy, resonance light
      scattering spectroscopy and molecular dynamics simulations, have been jointly
      used to achieve a deeper understanding of the degree of structural order in two
      geminal ionic liquids. In particular, 3,3'-di-n-butyl-1,1'-(1,3
      phenylenedimethylene)diimidazolium and 3,3'-di-n-butyl-1,1'-(1,4
      phenylenedimethylene)diimidazolium bis[bis(trifluoromethanesulfonyl)imide] have
      been studied. These geminal ionic liquids were chosen because of the presence of
      both a rigid phenylenedimethylene link between two imidazolium rings, which
      should give a high degree of order to the solvent system, and the different
      shapes of the two cations of the isomers, which could induce different properties
      and packing in the liquid state. Data collected here show that the two geminal
      ionic liquids are characterised by a different degree of structural order that
      induces, for example, a different sensitivity of the two solvent systems to
      temperature changes or to the presence of a co-solvent such as methanol.

PMID- 19844927
TI  - Light-driven charge separation in isoxazolidine-perylene bisimide dyads.
AB  - A series of arrays for light-driven charge separation is presented, in which
      perylene tetracarboxylic bisimide is the light-absorbing chromophore and electron
      acceptor, whereas isoxazolidines are colourless electron donors, the electron
      releasing properties of which are increased with respect to the amino group by
      means of the alpha-effect. Charge separation (CS) in toluene over a distance
      ranging from approximately 10 to approximately 16 A, with efficiencies of
      approximately 95 to approximately 50 % and CS lifetimes from 300 ps to 15 ns, are
      demonstrated. In dichloromethane the charge recombination reaction is faster than
      charge separation, preventing accumulation of the CS state. The effects of
      solvent polarity and molecular structure are discussed in the frame of current
      theories.

PMID- 19844928
TI  - A flexible approach to grandisine alkaloids: total synthesis of grandisines B, D,
      and F.
AB  - This article describes in detail the first total synthesis of grandisine
      alkaloids, grandisines B, D, and F, which show affinity for the human delta
      opioid receptor. The key steps in this synthesis are construction of the
      isoquinuclidinone moiety of 2 by intramolecular imine formation and the
      tetracyclic ring system of 4 by stereoselective ring closure of the enolate of
      amine 8 generated by 1,4-addition of ammonia to 9. Synthesis of key intermediate
      9 featured a highly stereoselective Bronsted acid mediated Morita-Baylis-Hillman
      (MBH) reaction via the N-acyl iminium ion.

PMID- 19844929
TI  - Role of environmental factors on the structure and spectroscopic response of 5'
      DNA-porphyrin conjugates caused by changes in the porphyrin-porphyrin
      interactions.
AB  - We have explored the utility, strength, and limitation of through-space exciton
      coupled circular dichroism in determination of the secondary structure of
      optically active chromophoric nanoarrays using the example of end-capped
      porphyrin- and metalloporphyrin-oligodeoxynucleotide conjugates. We put special
      emphasis on the explanation of the origin and significance of the distinctive
      multiple bands in the CD spectra (trisignate and tetrasignate CD bands). Such CD
      profiles are often observed in chiral aggregates or multichromophoric arrays but
      have never before been studied in detail. We found that variation of temperature
      and ionic strength has a profound effect on the geometry of the porphyrin-DNA
      conjugates and thus the nature of electronic interactions. At lower temperatures
      and in the absence of NaCl all three 5'-DNA-porphyrin conjugates display negative
      bisignate CD exciton couplets of variable intensity in the Soret region resulting
      from through-space interaction between the electric transition dipole moments of
      the two end-capped porphyrins. As the temperature is raised these exciton
      couplets are transformed into single positive bands originating from the
      porphyrin-single-strand DNA interactions. At higher ionic strengths and low
      temperatures, multisignate CD bands are observed in the porphyrin Soret region.
      These CD signature bands originate from a combination of intermolecular, end-to
      end porphyrin-porphyrin stacking between duplexes and porphyrin-DNA interactions.
      The intermolecular aggregation was confirmed by fluorescence and absorption
      spectroscopy and resonance light scattering. DeVoe theoretical CD calculations,
      in conjunction with molecular dynamics simulations and Monte Carlo conformational
      searches, were used to mimic the observed bisignate exciton-coupled CD spectra as
      well as multiple CD bands. Calculations correctly predicted the sign and shape of
      the experimentally observed CD spectra. These studies reveal that the exciton
      coupled circular dichroism is a very useful technique for the determination of
      the structure of optically active arrays.

PMID- 19844930
TI  - Nanoscale tungsten trioxide synthesized by in situ twin polymerization.

PMID- 19844931
TI  - Cortistatin A is a high-affinity ligand of protein kinases ROCK, CDK8, and CDK11.

PMID- 19844932
TI  - Energy transport along conjugated polymer chains with extended radiative
      lifetimes: a theoretical study.
AB  - The ability to improve exciton diffusion lengths is a key issue in optimizing
      many opto-electronic devices based on conjugated polymers. On the basis of
      quantum-chemical calculations, we investigate a strategy consisting of extending
      the radiative lifetime of energy carriers through incorporation along the polymer
      backbone of repeating units with forbidden optical transition. The results
      obtained for poly(p-phenylenebutadiyne), PPE, and poly(p-triphenylenebutadiyne),
      PTPE, show that the larger number of hops performed by the electronic excitations
      during their lifetime in PTPE is compensated by the smaller hopping length
      (associated with the reduced conjugation length), so that similar on-chain
      diffusion lengths are predicted in both polymers.

PMID- 19844933
TI  - Recombination of photogenerated lophyl radicals in imidazolium-based ionic
      liquids.
AB  - Laser flash photolysis is applied to study the recombination reaction of lophyl
      radicals in ionic liquids in comparison with dimethylsulfoxide as an example of a
      traditional organic solvent. The latter exhibits a similar micropolarity as the
      ionic liquids. The ionic liquids investigated are 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide (1), 1-hexyl-3-methylimidazolium
      hexafluorophosphate (2), and 1-butyl-3-methylimidazolium tetafluoroborate (3).
      The recombination of the photolytic generated lophyl radicals occur significantly
      faster in the ionic liquids than expected from their macroscopic viscosities and
      is a specific effect of these ionic liquids. On the other hand, this reaction can
      be compared with the macroscopic viscosity in the case of dimethylsulfoxide.
      Activation parameters obtained for lophyl radical recombination suggest
      different, anion-dependent mechanistic effects. Quantum chemical calculations
      based on density functional theory provide a deeper insight of the molecular
      properties of the lophyl radical and its precursor. Thus, excitation energies,
      spin densities, molar volumes, and partial charges are calculated. Calculations
      show a spread of spin density over the three carbon atoms of the imidazolyl
      moiety, while only low spin density is calculated for the nitrogens.

PMID- 19844934
TI  - Interaction of artemisinins with oxyhemoglobin Hb-FeII, Hb-FeII, carboxyHb-FeII,
      heme-FeII, and carboxyheme FeII: significance for mode of action and implications
      for therapy of cerebral malaria.
AB  - In line with the enhancement of antimalarial activities of the current clinical
      artemisinins against parasites cultured under CO, the artemisinins are unaffected
      in vitro by carboxyhemoglobin (CO-Hb-Fe(II)) or CO-heme-Fe(II), but are
      competitively decomposed by Hb-Fe(II) or heme-Fe(II). In the latter case, the
      heme studies are greatly facilitated by solubilization of the heme in aqueous
      medium by use of arginine. None of the Hb species has an appreciable effect on
      artemisone, or on other aminoartemisinins, and antimalarial activities are either
      less affected or remain essentially unchanged against parasites cultured under
      standard microaerophilic conditions or under CO. The findings not only indicate
      that artemisinins do not require Hb-Fe(II) or heme-Fe(II) for promotion of
      antimalarial activity, but are also important in relation to the therapy of
      severe/complicated or cerebral malaria.

PMID- 19844935
TI  - Perfluoro-tagged gold nanoparticles immobilized on fluorous silica gel: a
      reusable catalyst for the benign oxidation and oxidative esterification of
      alcohols.

PMID- 19844936
TI  - The next ten stories on antiviral drug discovery (part E): advents, advances, and
      adventures.
AB  - This review article presents the fifth part (part E) in the series of stories on
      antiviral drug discovery. The ten stories belonging to this fifth part are
      dealing with (i) aurintricarboxylic acid; (ii) alkenyldiarylmethanes; (iii) human
      immunodeficiency virus (HIV) integrase inhibitors; (iv) lens epithelium-derived
      growth factor as a potential target for HIV proviral DNA integration; (v) the
      status presens of neuraminidase inhibitors NAIs in the control of influenza virus
      infections; (vi) the status presens on respiratory syncytial virus inhibitors;
      (vii) tricyclic (1,N-2-ethenoguanine)-based acyclovir and ganciclovir
      derivatives; (viii) glycopeptide antibiotics as antivirals targeted at viral
      entry; (ix) the potential (off-label) use of cidofovir in the treatment of
      polyoma (JC and BK) virus infections; and (x) finally, thymidine phosphorylase as
      a target for both antiviral and anticancer agents.

PMID- 19844939
TI  - Noninvasive prenatal diagnosis of early onset primary dystonia I in maternal
      plasma.
AB  - OBJECTIVE: The genetic trait of a fetus may be determined early on in pregnancy
      using cell-free fetal DNA extracted from the plasma of pregnant women. The
      challenges for noninvasive diagnosis include the variable but still low amount of
      cell-free fetal DNA in the first trimester (57-761 gE/mL) and the competing high
      background of maternal DNA in the plasma ( approximately 90%). Prenatal detection
      of a paternally inherited dystonia 3 bp deletion mutation was undertaken using
      cell-free DNA (cfDNA) from the plasma of two at-risk pregnancies. The predicted
      fetal genotype was subsequently confirmed in each fetus. METHOD: Cell-free fetal
      DNA was extracted from the plasma of two pregnancies between 8 and 9 weeks'
      gestation as determined by fetal ultrasound scan. Analysis was by PCR
      amplification with size separation using polyacrylamide gel electrophoresis and
      detection by ethidium bromide staining. RESULTS: In both pregnancies the
      c.904_906delGAG DYT1 mutation was detected in the maternal plasma and then
      confirmed in the subsequent fetal tissue verifying that the fetus had inherited
      the paternal mutation. CONCLUSION: The detection of a paternally inherited DYT1
      mutation in maternal plasma was undertaken using simple, rapid, and inexpensive
      techniques with minimal risk of contamination. Further developments in the
      enrichment for fetal cfDNA will enhance the detection of point mutations in
      monogenic disorders.

PMID- 19844941
TI  - Placental growth hormone and growth hormone binding protein are first trimester
      maternal serum markers of Down syndrome.
AB  - BACKGROUND: Placental growth hormone (PGH) is synthesised by the placenta, and
      its function is modulated by growth hormone binding protein (GHBP). The potential
      of PGH and GHBP as maternal serum screening markers for Down syndrome (DS) was
      examined. MATERIALS AND METHODS: Maternal serum concentrations of PGH and GHBP
      were determined by ELISA in 74 DS and 261 control pregnancies in gestational week
      8(+0) to 13(+4). Log(10) MoM distributions of the markers were established. The
      performance of DS screening was estimated by Monte Carlo simulation. RESULTS: PGH
      log(10) MoM (SD) was decreased (p < 0.001) to -0.201 (0.373) and GHBP log(10) MoM
      to -0.116 (0.265) (p = 0.04), in DS pregnancies (n = 34) in week 8(+0) to 10(+0).
      In week 10(+1) to 13(+4), neither PGH (p = 0.16) nor GHBP (p = 0.13) was reduced
      in DS pregnancies. The detection rate (DR) for PGH in screening for DS in week
      8(+0) to 10(+0) was 39% for a false positive rate (FPR) of 5%; increasing to 72%
      in combination with PAPP-A + hCGbeta. PGH + GHBP in combination with PAPP-A +
      hCGbeta + nuchal translucency (NT) (CUB test) had a DR of 91% compared with 80%
      for the CUB test. CONCLUSION: PGH and GHBP are early first trimester maternal
      serum markers for DS [Correction made here after initial online publication].

PMID- 19844942
TI  - Placental protein 13 as a first trimester screening marker for aneuploidy.
AB  - OBJECTIVE: To determine whether Placental Protein 13 (PP13) could be an
      additional marker in first trimester screening for aneuploidies. METHODS: To
      evaluate differences in multiples of the gestation-specific normal median (MoMs),
      PP13 concentrations were measured in serum samples from Down syndrome, trisomy 18
      and 13 affected pregnancies and euploid singleton pregnancies (four for each case
      matched for duration of storage, maternal weight and age). RESULTS: The PP13 MoM
      in Down syndrome cases (n = 153) was 0.91 [not statistically significant from
      controls (n = 853); P = 0.06; Wilcoxon rank sum test, two-tail]. PP13 MoMs were
      decreased in trisomy 18 (n = 38-median MoM 0.64; P < 0.0001) and trisomy 13 cases
      (n = 23-median MoM 0.46; P < 0.0001). There was a slight upward trend in MoM
      values of the Down syndrome cases with gestational weeks. The PP13 MoM was
      significantly correlated with the pregnancy associated plasma protein-A MoM and
      the free beta-subunit of human chorion gonadotrophin (fbeta-hCG) MoM. CONCLUSION:
      PP13 does not seem to be a good marker for Down syndrome. PP13 MoMs are, however,
      significantly lower in trisomy 18 and 13 pregnancies. The addition of PP13 to the
      current screening test could be valuable for improving the discrimination of
      aneuploid from euploid pregnancies.

PMID- 19844943
TI  - NSAID switching and short-term gastrointestinal outcome rates after the
      withdrawal of rofecoxib.
AB  - OBJECTIVE: The consequences of the rofecoxib withdrawal on upper GI toxicity are
      largely unknown. We sought to estimate the effect of switching from selective Cox
      2 inhibitors to non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) on
      the incidence of upper GI adverse events following the withdrawal of rofecoxib on
      30 September 2004. METHODS: We identified a cohort of 33 045 patients with
      arthritis and chronic use of any selective Cox-2 inhibitor during the 6 months
      before the withdrawal of rofecoxib in claims data from several US health plans.
      We calculated monthly rates of hospitalization for upper GI adverse events or
      upper GI endoscopy for the 6 months before and 3 months after the switching and
      compared the time trends in outcomes. RESULTS: In the subgroup of 15 916 patients
      using rofecoxib immediately before its withdrawal, 2626 (17%) switched to
      nsNSAIDs without co-prescribing of a gastroprotective drug, 146 (1%) with a
      gastroprotective drug, and 5246 (33%) switched to either celecoxib or valdecoxib.
      Among those switching to nsNSAID without gastroprotection, time trends of upper
      GI hospitalization rates and endoscopies did not significantly increase compared
      with those switching to celecoxib or valdecoxib (+0.3 per 1000 per month; 95%CI 
      3.0 to 3.5). The visit rate for peptic ulcer disease (PUD) increased more in the
      group switching to nsNSAIDs without gastroprotection (+5.2 visits per 1000 per
      month; 1.2-9.2) compared with the group switching to another coxib. CONCLUSIONS:
      Short-term follow-up data suggest that the sudden shift from rofecoxib to
      nsNSAIDs without gastroprotection did not increase the rate of hospitalization
      for GI complications but increased outpatient visits for PUD.

PMID- 19844944
TI  - Selection and bias--two hostile brothers.
AB  - We consider the situation where in a first stage of a clinical trial several
      treatments are compared with a single control and the 'best' treatment(s) are
      selected in an interim analysis to be carried on to the second stage. We quantify
      the mean bias and mean square error of the conventional estimates after selection
      depending on the number of treatments and the selection time during the trial.
      The cases without or with reshuffling the planned sample size of the dropped
      treatments to the selected ones are investigated. The mean bias shows very
      different patterns depending on the selection rule and the unknown parameter
      values. We stress the fact that the quantification of the bias is possible only
      in designs with planned adaptivity where the design allows reacting to new
      evidence, but the decision rules are laid down in advance. Finally, we calculate
      the mean bias which arises in a simple but influential regulatory selection rule,
      to register a new medical therapy only when two pivotal trials have both proven
      an effect by a statistical test.

PMID- 19844945
TI  - Validation of diagnostic codes for outpatient-originating sudden cardiac death
      and ventricular arrhythmia in Medicaid and Medicare claims data.
AB  - PURPOSE: Sudden cardiac death (SD) and ventricular arrhythmias (VAs) caused by
      medications have arisen as an important public health concern in recent years.
      The validity of diagnostic codes in identifying SD/VA events originating in the
      ambulatory setting is not well known. This study examined the positive predictive
      value (PPV) of hospitalization and emergency department encounter diagnoses in
      identifying SD/VA events originating in the outpatient setting. METHODS: We
      selected random samples of hospitalizations and emergency department claims with
      principal or first-listed discharge diagnosis codes indicative of SD/VA in
      individuals contributing at least 6 months of baseline time within 1999-2002
      Medicaid and Medicare data from five large states. We then obtained and reviewed
      medical records corresponding to these events to serve as the reference standard.
      RESULTS: We identified 5239 inpatient and 29 135 emergency department events,
      randomly selected 100 of each, and obtained 119 medical records, 116 of which
      were for the requested courses of care. The PPVs for an outpatient-originating
      SD/VA precipitating hospitalization or emergency department treatment were 85.3%
      (95% confidence interval [CI] = 77.6-91.2) overall, 79.7% (95%CI = 68.3-88.4) for
      hospitalization claims, and 93.6% (95%CI = 82.5-98.7) for emergency department
      claims. CONCLUSIONS: First-listed SD/VA diagnostic codes identified in inpatient
      or emergency department encounters had very good agreement with clinical
      diagnoses and functioned well to identify outpatient-originating events.
      Researchers using such codes can be confident of the PPV when conducting studies
      of SD/VA originating in the outpatient setting.

PMID- 19844946
TI  - Missing data: discussion points from the PSI missing data expert group.
AB  - The Points to Consider Document on Missing Data was adopted by the Committee of
      Health and Medicinal Products (CHMP) in December 2001. In September 2007 the CHMP
      issued a recommendation to review the document, with particular emphasis on
      summarizing and critically appraising the pattern of drop-outs, explaining the
      role and limitations of the 'last observation carried forward' method and
      describing the CHMP's cautionary stance on the use of mixed models. In
      preparation for the release of the updated guidance document, statisticians in
      the Pharmaceutical Industry held a one-day expert group meeting in September
      2008. Topics that were debated included minimizing the extent of missing data and
      understanding the missing data mechanism, defining the principles for handling
      missing data and understanding the assumptions underlying different analysis
      methods. A clear message from the meeting was that at present, biostatisticians
      tend only to react to missing data. Limited pro-active planning is undertaken
      when designing clinical trials. Missing data mechanisms for a trial need to be
      considered during the planning phase and the impact on the objectives assessed.
      Another area for improvement is in the understanding of the pattern of missing
      data observed during a trial and thus the missing data mechanism via the plotting
      of data; for example, use of Kaplan-Meier curves looking at time to withdrawal.

PMID- 19844947
TI  - Where are the autism economists?

PMID- 19844948
TI  - The ligand-binding b' domain of human protein disulphide-isomerase mediates
      homodimerization.
AB  - Purified preparations of the recombinant b'x domain fragment of human protein
      disulphide isomerase (PDI), which are homogeneous by mass spectrometry and sodium
      dodecyl sulfate polyacrylamide gel electrophoresis, comprise more than one
      species when analyzed by ion-exchange chromatography and nondenaturing
      polyacrylamide gel electrophoresis. These species were resolved and shown to be
      monomer and dimer by analytical ultracentrifugation and analytical size-exclusion
      chromatography. Spectroscopic properties indicate that the monomeric species
      corresponds to the "capped" conformation observed in the x-ray structure of the
      I272A mutant of b'x (Nguyen, Wallis, Howard, Haapalainen, Salo, Saaranen, Sidhu,
      Wierenga, Freedman, Ruddock, and Williamson, J Mol Biol 2008;383:1144-1155) in
      which the x region binds to a hydrophobic patch on the surface of the b' domain;
      conversely, the dimeric species has an "open" or "uncapped" conformation in which
      the x region does not bind to this surface. The larger bb'x fragment of human PDI
      shows very similar behavior to b'x and can be resolved into a capped monomeric
      species and an uncapped dimer. Preparations of recombinant b' domain of human PDI
      and of the bb' domain pair are found exclusively as dimers. Full-length PDI is
      known to comprise a mixture of monomeric and dimeric species, whereas the
      isolated a, b, and a' domains of PDI are found exclusively as monomers. These
      results show that the b' domain of human PDI tends to form homodimers--both in
      isolation and in other contexts--and that this tendency is moderated by the
      adjacent x region, which can bind to a surface patch on the b' domain.

PMID- 19844949
TI  - Influence of the polymer-micelle interaction on micelle-substrate binding.
AB  - In an attempt to investigate how a nonionic polymer, hydroxypropyl
      methylcellulose (HPMC), interacts with a cationic surfactant,
      hexadecyltrimethylammonium bromide (CTAB), a dialysis method was employed for
      directly measuring the HPMC-CTAB interaction. The result showed that an
      interaction existed between CTAB and HPMC, and the higher the HPMC concentration
      the greater the fraction of CTAB bound. The shift in the UV spectra represents
      the change in the microenvironment. UV spectroscopy was employed to indicate the
      location of substrates, alpha-NA, IBA, and oil red O, in the CTAB micelles. The
      study of solubility as a function of CTAB concentration was the method used for
      determining the binding constants of the substrates. The addition of HPMC
      decreased the binding constants of the substrates to the micelles. It implied
      that the HPMC-CTAB interaction influenced the substrate binding regions. The IBA
      binding constant was also determined using a potentiometric titration method. The
      results agreed well between the two methods.

PMID- 19844950
TI  - Very rapid dissolution is not needed to guarantee bioequivalence for
      biopharmaceutics classification system (BCS) I drugs.
AB  - Currently, the EMEA, FDA, and WHO as regulatory authorities accept rapidly
      dissolving (>85% dissolved in 30 min) biopharmaceutics classification system
      (BCS) I drug products for biowaiver candidates. In the draft EMEA guideline the
      requirement has been set tighter, that is, the drug product should be very
      rapidly dissolving (>85% dissolved in 15 min) to be eligible for a biowaiver.
      Pharmacokinetic modeling of 32 BCS I drugs was performed to demonstrate that very
      rapid dissolution is not necessary to guarantee bioequivalence for them. Rapid
      dissolution and similar dissolution profiles are sufficient criteria for all BCS
      I drugs.

PMID- 19844951
TI  - Dissection of a beta-barrel motif leads to a functional dimer: the case of the
      intestinal fatty acid binding protein.
AB  - A lingering issue in the area of protein engineering is the optimal design of
      beta motifs. In this regard, the framework provided by intestinal fatty acid
      binding protein (IFABP) was successfully chosen to explore the consequences on
      structure and function of the redesign of natural motifs. A truncated form of
      IFABP (Delta 98 Delta) served to illustrate the nonintuitive notion that the
      integrity of the beta-barrel can indeed be compromised with no effect on the
      ability to attain a native-like fold. This is most likely the outcome of the key
      role played by the preservation of essential core residues. In the search for the
      minimal structural determinants of this fold, Delta 98 Delta offered room for
      further intervention. A dissection of this protein leads to a new abridged
      variant, Delta 78 Delta, containing 60% of the amino acids of IFABP.
      Spectroscopic analyses indicate that Delta 78 Delta retains substantial beta
      sheet content and preserves tertiary interactions, displaying cooperative
      unfolding and binding activity. Most strikingly, this construct adopts a
      remarkably stable dimeric structure in solution. This phenomenon takes advantage
      of the inherent structural plasticity of this motif, likely profitting from edge
      to-edge interactions between beta-sheets, whereas avoiding the most commonly
      occurring outcome represented by aggregation.

PMID- 19844953
TI  - DNA damage and oxidative stress in human liver cell L-02 caused by surface water
      extracts during drinking water treatment in a waterworks in China.
AB  - Because of the daily and life-long exposure to disinfection by-products formed
      during drinking water treatment, potential adverse human health risk of drinking
      water disinfection is of great concern. Toxicological studies have shown that
      drinking water treatment increases the genotoxicity of surface water. Drinking
      water treatment is comprised of different potabilization steps, which greatly
      influence the levels of genotoxic products in the surface water and thus may
      alter the toxicity and genotoxicity of surface water. The aim of the present
      study was to understand the influence of specific steps on toxicity and
      genotoxicity during the treatment of surface water in a water treatment plant
      using liquid chlorine as the disinfectant in China. An integrated approach of the
      comet and oxidative stress assays was used in the study, and the results showed
      that both the prechlorination and postchlorination steps increased DNA damage and
      oxidative stress caused by water extracts in human derived L-02 cells while the
      tube settling and filtration steps had the opposite effect. This research also
      highlighted the usefulness of an integrated approach of the comet and oxidative
      stress assays in evaluating the genotoxicity of surface water during drinking
      water treatment.

PMID- 19844952
TI  - Organization of the posterior parietal cortex in galagos: II. Ipsilateral
      cortical connections of physiologically identified zones within anterior
      sensorimotor region.
AB  - We studied cortical connections of functionally distinct movement zones of the
      posterior parietal cortex (PPC) in galagos identified by intracortical
      microstimulation with long stimulus trains ( approximately 500 msec). All these
      zones were in the anterior half of PPC, and each of them had a different pattern
      of connections with premotor (PM) and motor (M1) areas of the frontal lobe and
      with other areas of parietal and occipital cortex. The most rostral PPC zone has
      major connections with motor and visuomotor areas of frontal cortex as well as
      with somatosensory areas 3a and 1-2 and higher order somatosensory areas in the
      lateral sulcus. The dorsal part of anterior PPC region representing hand-to-mouth
      movements is connected mostly to the forelimb representation in PM, M1, 3a, 1-2,
      and somatosensory areas in the lateral sulcus and on the medial wall. The more
      posterior defensive and reaching zones have additional connections with
      nonprimary visual areas (V2, V3, DL, DM, MST). Ventral aggressive and defensive
      face zones have reciprocal connections with each other as well as connections
      with mostly face, but also forelimb representations of premotor areas and M1 as
      well as prefrontal cortex, FEF, and somatosensory areas in the lateral sulcus and
      areas on the medial surface of the hemisphere. Whereas the defensive face zone is
      additionally connected to nonprimary visual cortical areas, the aggressive face
      zone is not. These differences in connections are consistent with our functional
      parcellation of PPC based on intracortical long-train microstimulation, and they
      identify parts of cortical networks that mediate different motor behaviors.

PMID- 19844954
TI  - Effect of O6-chloroethylguanine DNA lesions on the kinetics and mechanism of
      micronucleus induction in vivo.
AB  - The aim of this work was to determine the kinetics of micronucleus production
      because of an increase in O(6)-chloroethyl guanine (O6-ChlEt-G) DNA lesions in
      murine bone marrow cells in vivo. We increased the frequency of O6-ChlEt-G
      lesions by pretreatment with an inhibitor of O(6)-methylguanine-DNA
      methyltransferase (MGMT), O(6)-benzylguanine (O6BG), and subsequent treatment
      with bis-chloroethylnitrosourea (BCNU). The kinetics of micronucleated
      polychromatic erythrocyte (MN-PCE) induction was established by scoring the
      frequency of MN-PCEs per 2000 PCEs in peripheral blood at 8-hr intervals from
      immediately prior to treatment to 72-hr post-treatment. We examined groups of
      five mice treated with (i) dimethylsulfoxide (DMSO), (ii) O6BG in DMSO, (iii)
      BCNU, or (iv) O6BG in DMSO plus BCNU. The data indicate that O6BG pretreatment
      causes: (i) ian increase in MN-PCEs induced by BCNU, (ii) a delay in the time of
      maximal MN-PCE induction produced by the different BCNU doses, and (iii) an
      increase in cytotoxicity. These data confirm that O6-ChlEt-G is a lesion involved
      in DNA break induction and in the subsequent production of micronuclei, and also
      that these lesions seem to be stoichiometrically reduced by MGMT. These data also
      show that induction of MN-PCEs by BCNU is delayed by pretreatment with O6BG for
      more than 6 hr, perhaps due to the time required for repair of crosslinks derived
      from O6-ChlEt-G and/or for DNA duplication, which is required for adduct
      transformation into crosslinks.

PMID- 19844955
TI  - Excretion characteristics of urinary 8-hydroxydeoxyguanosine after dietary
      exposure to polycyclic aromatic hydrocarbons.
AB  - Urinary 8-hydroxydeoxyguanosine (8-OHdG) is considered a noninvasive marker for
      oxidative stress and also a marker of carcinogenic potential for compounds such
      as polycyclic aromatic hydrocarbons (PAHs). Although human studies have
      investigated urinary 8-OHdG concentrations in PAH-exposed workers and the general
      population, the background level and excretion kinetics of urinary 8-OHdG in
      humans remain unclear. Two feeding experiments (consumption of barbecued meat of
      15 and 30 g/kg for Experiments 1 and 2, respectively) were conducted to examine
      the excretion characteristics of urinary 8-OHdG. All urine voided over 7 days was
      collected, but only first morning (approximately 8 A.M.) and last afternoon
      (approximately 5 P.M.) samples were analyzed for 8-OHdG. Mean background urinary
      8-OHdG concentration was 4.76 microg/g creatinine. Statistically significant
      increases (P < 0.05) in urinary 8-OHdG concentration were observed on the
      afternoon of the 3rd and 2nd days after barbecued meat consumption for
      Experiments 1 and 2, respectively. A pattern of diurnal fluctuation (P < 0.05) in
      8-OHdG excretion rate was evident, in that the excretion of 8-OHdG was faster
      during the night than during the day. Additionally, significant (P < 0.05) and
      strong (r > 0.6) correlations were found between urinary 8-OHdG measured 2-3 days
      after exposure to barbecued meat, and 1-hydroxypyrene (1-OHP) and 3-hydroxy
      benzo[a]pyrene (3-OHBaP) concentrations measured within a half day after such
      exposure. The current results demonstrate a lag in excretion of urinary 8-OHdG
      relative to 1-OHP and 3-PHBaP after dietary PAH exposure. These relationships
      highlight the importance of sampling time when assessing PAH-related DNA lesions
      through urinary 8-OHdG.

PMID- 19844956
TI  - Structural and functional characterization of a triple mutant form of S100A7
      defective for Jab1 binding.
AB  - S100A7 (psoriasin) is a calcium- and zinc-binding protein implicated in breast
      cancer. We have shown previously that S100A7 enhances survival mechanisms in
      breast cells through an interaction with c-jun activation domain binding protein
      1 (Jab1), and an engineered S100A7 triple mutant (Asp(56)Gly, Leu(78)Met, and
      Gln(88)Lys-S100A7(3)) ablates Jab1 binding. We extend these results to include
      defined breast cancer cell lines and demonstrate a disrupted S100A7(3)/Jab1
      phenotype is maintained. To establish the basis for the abrogated Jab1 binding,
      we have recombinantly produced S100A7(3), demonstrated that it retains the
      ability to form an exceptionally thermostable dimer, and solved the three
      dimensional crystal structure to 1.6 A. Despite being positioned at the dimer
      interface, the Leu(78)Met mutation is easily accommodated and contributes to a
      methionine-rich pocket formed by Met(12), Met(15), and Met(34). In addition to
      altering the surface charge, the Gln(88)Lys mutation results in a nearby
      rotameric shift in Tyr(85), leading to a substantially reorganized surface cavity
      and may influence zinc binding. The final mutation of Asp(56) to Gly results in
      the largest structural perturbation shortening helix IV by one full turn. It is
      noteworthy that position 56 lies in one of two divergent clusters between S100A7
      and the functionally distinct yet highly homologous S100A15. The structure of
      S100A7(3) provides a unique perspective from which to characterize the S100A7
      Jab1 interaction and better understand the distinct functions between S100A7, and
      it is closely related paralog S100A15.

PMID- 19844957
TI  - Colocolic intussusception in a patient with ulcerative colitis.

PMID- 19844959
TI  - Solid-state stability of spray-dried insulin powder for inhalation: chemical
      kinetics and structural relaxation modeling of Exubera above and below the glass
      transition temperature.
AB  - The effect of temperature on the chemical stability of an amorphous spray-dried
      insulin powder formulation (Exubera) was evaluated in the solid state at constant
      moisture content. The chemical stability of the powder was assessed using
      reversed-phase high-performance liquid chromatography (RP-HPLC) and high
      performance-size exclusion chromatography (HP-SEC). The major degradants in spray
      dried insulin produced during heat stressing were identified as A21
      desamidoinsulin (A21) and high molecular weight protein (HMWP). As expected, the
      rates of formation of A21 and HMWP were observed to increase with temperature. A
      stretched-time kinetic model (degradation rate is proportional to the square root
      of time) was applied to the degradant profiles above and below the glass
      transition temperature (T(g)) and apparent reaction rate constants were
      determined. Below T(g), isothermal enthalpy of relaxation measurements were used
      to assess the effect of temperature on molecular mobility. The formation of A21
      and HMWP was found to follow an Arrhenius temperature dependence above and below
      the T(g). Comparison of reaction rate constants to those estimated from
      structural relaxation experiments suggests that the reaction pathways to form A21
      and HMWP below the T(g) may be coupled with the molecular motions involved in
      structural relaxation.

PMID- 19844960
TI  - Decision making in depression: differences in decisional conflict between healthy
      and depressed individuals.
AB  - This study investigated differences in the emergence of decisional conflict in
      healthy and depressed participants. The two groups of interest were questioned
      about their experience of decisional conflict and ongoing thoughts and
      impressions during decision making. As predicted, depressed participants
      experienced more decisional conflict than healthy participants. Furthermore, the
      diverse processes hypothesis was supported: In healthy participants,
      preoccupation with the task was the only predictor of decisional conflict. In
      depressed participants, decisional conflict was predicted by a combination of
      depression-related processes (e.g., low self-efficacy, lack of concentration,
      rumination, etc.). This research reduces the gap between the relevance of the
      symptom of indecisiveness (e.g., for diagnostic purposes) and the lack of
      knowledge in this realm of psychopathology.

PMID- 19844961
TI  - Method development for direct detection of glycoproteins on aminophenylboronic
      acid functionalized self-assembled monolayers by matrix-assisted laser
      desorption/ionization mass spectrometry.

PMID- 19844962
TI  - Precursor ion scans for the targeted detection of stable-isotope-labeled
      peptides.
AB  - Stable isotope labels are routinely introduced into proteomes for quantification
      purposes. Full labeling of cells in varying biological states, followed by sample
      mixing, fractionation and intensive data acquisition, is used to obtain accurate
      large-scale quantification of total protein levels. However, biological processes
      often affect only a small group of proteins for a short time, resulting in
      changes that are difficult to detect against the total proteome background. An
      alternative approach could be the targeted analysis of the proteins synthesized
      in response to a given biological stimulus. Such proteins can be pulse-labeled
      with a stable isotope by metabolic incorporation of 'heavy' amino acids. In this
      study we investigated the specific detection and identification of labeled
      proteins using acquisition methods based on Precursor Ion Scans (PIS) on a triple
      quadrupole ion trap mass spectrometer. PIS-based methods were set to detect
      unique immonium ions originating from labeled peptides. Different labels and
      methods were tested in standard mixtures to optimize performance. We showed that,
      in comparison with an untargeted analysis on the same instrument, the approach
      allowed a several-fold increase in the specificity of detection of labeled
      proteins over unlabeled ones. The technique was applied to the identification of
      proteins secreted by human cells into growth media containing bovine serum
      proteins, allowing the preferential detection of labeled cellular proteins over
      unlabeled bovine ones. However, compared with untargeted acquisitions on two
      different instruments, the PIS-based strategy showed some limitations in
      sensitivity. We discuss possible perspectives of the technique.

PMID- 19844963
TI  - Use of ion mobility mass spectrometry and a collision cross-section algorithm to
      study an organometallic ruthenium anticancer complex and its adducts with a DNA
      oligonucleotide.
AB  - We report the development of an enhanced algorithm for the calculation of
      collision cross-sections in combination with Travelling-Wave ion mobility mass
      spectrometry technology and its optimisation and evaluation through the analysis
      of an organoruthenium anticancer complex [(eta6-biphenyl)Ru(II)(en)Cl]+.
      Excellent agreement was obtained between the experimentally determined and
      theoretically determined collision cross-sections of the complex and its major
      product ion formed via collision-induced dissociation. Collision cross-sections
      were also experimentally determined for adducts of this ruthenium complex with
      the single-stranded oligonucleotide hexamer d(CACGTG). Ion mobility tandem mass
      spectrometry measurements have allowed the binding sites for ruthenium on the
      oligonucleotide to be determined.

PMID- 19844964
TI  - Rapid drug detection in oral samples by porous silicon assisted laser
      desorption/ionization mass spectrometry.
AB  - The demand for analysis of oral fluid for illicit drugs has arisen with the
      increased adoption of roadside testing, particularly in countries where changes
      in legislation allow random roadside testing of drivers for the presence of a
      palette of illicit drugs such as methamphetamine (MA), 3,4
      methylenedioxymethamphetamine (MDMA) and Delta9-tetrahydrocannabinol (THC). Oral
      samples are currently tested for such drugs at the roadside using an immunoassay
      based commercial test kit. Positive roadside tests are sent for confirmatory
      laboratory analysis, traditionally by means of gas chromatography/mass
      spectrometry (GC/MS). We present here an alternative rapid analysis technique,
      porous silicon assisted laser desorption/ionization time-of-flight mass
      spectrometry (pSi LDI-MS), for the high-throughput analysis of oral fluids. This
      technique alleviates the need for sample derivatization, requires only sub
      microliter sample volumes and allows fast analysis (of the order of seconds). In
      this study, the application of the technique is demonstrated with real samples
      from actual roadside testing. The analysis of oral samples resulted in detection
      of MA and MDMA with no extraction and analysis of THC after ethyl acetate
      extraction. We propose that, subject to miniaturization of a suitable mass
      spectrometer, this technique is well suited to underpin the deployment of oral
      fluid testing in the clinic, workplace and on the roadside.

PMID- 19844965
TI  - Rapid simultaneous quantitative determination of different small pharmaceutical
      drugs using a conventional matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry system.
AB  - The present study establishes a simple, rapid and sensitive method for the
      simultaneous quantification of different small pharmaceutical drugs using a
      matrix-assisted laser desorption/ionization source (MALDI) coupled with a time-of
      flight (TOF) mass analyzer. Neither time-consuming sample preparation, nor
      special target plates, isotopically labelled internal standards or other extra
      equipment are necessary. A simple standard dried-droplet preparation with the
      common matrix alpha-cyano-4-hydroxycinnamic acid (CHCA) was used. The background
      signals of CHCA in the low-mass region did not pose the presumed problem, because
      the sensitivity, resolution and mass accuracy of a modern MALDI-TOF MS system is
      sufficient to overcome this difficulty. Four experiments were performed in order
      to verify the quantification method. First, ten different phenothiazines were
      quantified in the range of 5-2000 nM (1-880 ng/mL). A good precision (relative
      standard deviation (RSD) 4.4-9.3%), linearity (R2 >0.99) and accuracy (error 4.7
      11%) was obtained in all cases. Additionally, simultaneous quantification of
      these ten phenothiazines was carried out in human plasma without prior
      chromatographic separation in the range of 2-1750 ng/mL yielding good linearity,
      precision and accuracy (mean RSD 7.6%; R2 >0.99, mean error 8.0%). Accordingly, a
      quantitative analysis of ten chemically and pharmaceutically unrelated drugs was
      performed in the same way. A comparable linearity (R2 >0.99), precision (mean RSD
      7.6%) and accuracy (mean error 8.3%) was obtained in the range of 5-2000 nM.
      Finally, the prazosin content of a commercial tablet was directly determined
      without further purification steps.

PMID- 19844966
TI  - Peptide-binding specificity of the prosurfactant protein C Brichos domain
      analyzed by electrospray ionization mass spectrometry.
AB  - The C-terminal domain of lung surfactant protein C (CTC) precursor (proSP-C) is
      involved in folding of the transmembrane segment of proSP-C. CTC includes a
      Brichos domain with homologs in cancer- and dementia-associated proteins.
      Mutations in the Brichos domain cause misfolding of proSP-C and hence amyloid
      fibril formation in interstitial lung disease. Electrospray ionization mass
      spectrometry (ESI-MS) with collision-induced dissociation (CID) experiments was
      applied to study non-covalent interactions between human recombinant CTC or its
      Brichos domain, and SP-C analogs, homotripeptides and peptides designed to model
      amyloid fibril formation. The results show that the Brichos domain contains the
      peptide-binding function of CTC. In titration experiments, apparent dissociation
      constants (KD) were in the micromolar range where triple-valine showed the lowest
      KD and triple-tyrosine the highest. Non-hydrophobic peptides failed to form
      complexes with Brichos. CID revealed that complexes with aromatic peptide ligands
      are more stable in the gas phase than complexes with non-aromatic ligands. The
      Brichos domain was also shown to bind fibril-forming peptides containing
      aromatic/hydrophobic residues.

PMID- 19844967
TI  - Determination of K-Ar ages in milligram samples using an infrared laser for argon
      extraction.
AB  - The K-Ar dating method has been used for decades to decipher the ages of
      terrestrial and extraterrestrial minerals and rocks. The natural radioactive
      decay of a metal to a rare gas is an advantage that allows the determination of
      very small amounts of argon by mass spectrometry. Although the Ar-Ar method has
      superseded K-Ar, the latter is still used and it has room for improvement. One of
      these is the reduction of the analyzed sample mass, a desideratum of any current
      analytical technique. I report here our experience in K-Ar geochronology of
      milligram-sized samples using laser heating and melting for gas extraction. This
      modification of the classical K-Ar technique has not been, to my knowledge, used
      in any other laboratory in the world and deserves a detailed description of its
      advantages and limitations.

PMID- 19844968
TI  - Nicotine, acetanilide and urea multi-level 2H-, 13C- and 15N-abundance reference
      materials for continuous-flow isotope ratio mass spectrometry.
AB  - Accurate determinations of stable isotope ratios require a calibration using at
      least two reference materials with different isotopic compositions to anchor the
      isotopic scale and compensate for differences in machine slope. Ideally, the
      delta values of these reference materials should bracket the isotopic range of
      samples with unknown delta values. While the practice of analyzing two
      isotopically distinct reference materials is common for water (VSMOW-SLAP) and
      carbonates (NBS 19 and L-SVEC), the lack of widely available organic reference
      materials with distinct isotopic composition has hindered the practice when
      analyzing organic materials by elemental analysis/isotope ratio mass spectrometry
      (EA-IRMS). At present only L-glutamic acids USGS40 and USGS41 satisfy these
      requirements for delta13C and delta15N, with the limitation that L-glutamic acid
      is not suitable for analysis by gas chromatography (GC). We describe the
      development and quality testing of (i) four nicotine laboratory reference
      materials for on-line (i.e. continuous flow) hydrogen reductive gas
      chromatography-isotope ratio mass-spectrometry (GC-IRMS), (ii) five nicotines for
      oxidative C, N gas chromatography-combustion-isotope ratio mass-spectrometry (GC
      C-IRMS, or GC-IRMS), and (iii) also three acetanilide and three urea reference
      materials for on-line oxidative EA-IRMS for C and N. Isotopic off-line
      calibration against international stable isotope measurement standards at Indiana
      University adhered to the 'principle of identical treatment'. The new reference
      materials cover the following isotopic ranges: delta2H(nicotine) -162 to -45 per
      thousand, delta13C(nicotine) -30.05 to +7.72 per thousand, delta15N(nicotine) 
      6.03 to +33.62 per thousand; delta15N(acetanilide) +1.18 to +40.57 per thousand;
      delta13C(urea) -34.13 to +11.71 per thousand, delta15N(urea) +0.26 to +40.61 per
      thousand (recommended delta values refer to calibration with NBS 19, L-SVEC, IAEA
      N-1, and IAEA-N-2). Nicotines fill a gap as the first organic nitrogen stable
      isotope reference materials for GC-IRMS that are available with different
      delta15N values. Comparative delta13C and delta15N on-line EA-IRMS data from 14
      volunteering laboratories document the usefulness and reliability of acetanilides
      and ureas as EA-IRMS reference materials.

PMID- 19844969
TI  - Use of liquid chromatography/tandem mass spectrometric molecular fingerprinting
      for the rapid structural identification of pharmaceutical impurities.
AB  - Use of liquid chromatography/tandem mass spectrometric (LC/MS(n)) molecular
      fingerprinting is systematically demonstrated as a very effective tool for rapid
      structural elucidation of pharmaceutical impurities through a case study in which
      three isomers of betamethasone sodium phosphate (BSP) were rapidly identified as
      degradants formed due to the D-homoannular ring expansion of the steroid core
      structure of BSP in the solid state. The rapid structural elucidation of these
      degradants was achieved by matching or closely matching the UV profiles,
      molecular weights, and more importantly the fragmentation patterns obtained from
      the LC/MS(n) (n = 1 to 3) analysis of their enzyme-catalyzed hydrolytic products,
      respectively, with those of a D-homoannular isomer of betamethasone available in
      our LC/MS(n) molecular fingerprint database. This strategy of using LC/MS(n)
      molecular fingerprinting to obtain high-confidence structures of unknown species
      is then validated by structure verification through one- (1D) and two-dimensional
      (2D) nuclear magnetic resonance (NMR) experiments.

PMID- 19844970
TI  - Screening strategy for the rapid detection of in vitro generated glutathione
      conjugates using high-performance liquid chromatography and low-resolution mass
      spectrometry in combination with LightSight software for data processing.
AB  - The knowledge of drug metabolism in the early phases of the drug discovery
      process is vital for minimising compound failure at later stages. As chemically
      reactive metabolites may cause adverse drug reactions, it is generally accepted
      that avoiding formation of reactive metabolites increases the chances of success
      of a molecule. In order to generate this important information, a screening
      strategy for the rapid detection of in vitro generated reactive metabolites
      trapped by glutathione has been developed. The bioassay incorporated the use of
      native glutathione and its close analogue the glutathione ethyl ester. The
      generic conditions for detecting glutathione conjugates that undergo constant
      neutral loss of 129 Da were optimised using a glutathione-based test mix of four
      compounds. The final liquid chromatography/tandem mass spectrometry constant
      neutral loss method used low-resolution settings and a scanning window of 200
      amu. Data mining was rapidly and efficiently performed using LightSight software.
      Unambiguous identification of the glutathione conjugates was significantly
      facilitated by the analytical characteristics of the conjugate pairs formed with
      glutathione and glutathione ethyl ester, i.e. by chromatographic retention time
      and mass differences. The reliability and robustness of the screening strategy
      was tested using a number of compounds known to form reactive metabolites.
      Overall, the developed screening strategy provided comprehensive and reliable
      identification of glutathione conjugates and is well suited for rapid routine
      detection of trapped reactive metabolites. This new approach allowed the
      identification of a previously unreported diclofenac glutathione conjugate.

PMID- 19844971
TI  - Validation of deuterium and oxygen18 in urine and saliva samples from children
      using on-line continuous-flow isotope ratio mass spectrometry.
AB  - The doubly labelled water method is valuable for measuring energy expenditure in
      humans. It usually involves blood or urine sampling, which might be difficult in
      neonates and children with cerebral palsy or other disabilities. We therefore
      aimed to validate a method making use of saliva samples analyzed by automated
      thermal conversion elemental analyzer in combination with isotope ratio mass
      spectrometry (TC-EA/IRMS). The subjects received labelled water orally and urine
      and saliva samples were collected and analyzed. Deuterium as well as oxygen18 was
      measured in one single run using a peak jump method. Excellent linearity was
      found for measurement of enrichments of deuterium (R2 = 0.9999) and oxygen18 (R2
      = 0.9999). The intra-assay precision and the inter-assay precision of the
      measurement of two standards were good for both deuterium and oxygen18. The
      variation between urine and saliva samples was small (4.83% for deuterium and
      2.33% for oxygen18 n = 40). Saliva sampling is to be preferred, therefore, as it
      can be easily collected and is non-invasive. Moreover, its time of production is
      almost exactly known. The TC-EA/IRMS method is a good alternative to the more
      laborious off-line IRMS measurements.

PMID- 19844972
TI  - Compound-specific delta18O analyses of neutral sugars in soils using gas
      chromatography-pyrolysis-isotope ratio mass spectrometry: problems, possible
      solutions and a first application.
AB  - Although gas chromatography-pyrolysis-isotope ratio mass spectrometry (GC-Py
      IRMS) has allowed us to make online compound-specific delta18O measurements for
      about the last ten years, this technique has hardly been applied. We tested
      different pyrolysis reactor designs using standards (vanillin, ethylvanillin, a
      fatty acid methyl ester and alkanes) in order to optimize the GC-Py-IRMS delta18O
      measurements. The method was then applied to methylboronic acid (MBA) sugar
      derivatives (pentoses, 6-deoxyhexoses and hexoses). Plant- and microbial-derived
      monosaccharides were extracted hydrolytically from litter and topsoils before
      derivatization. The measured delta18O values of samples and co-analyzed reference
      material were first drift-corrected by use of regularly discharged pulses of CO
      reference gas. Secondly, they were corrected for the amount dependence of the
      delta18O values. Thirdly, the delta18O values were calibrated using the reference
      material (principle of 'Identical Treatment'), and, finally, a correction was
      applied by taking the hydrolytically introduced and water-exchangeable oxygen
      atoms into account. Our results suggest that the delta18O values of plant-derived
      monosaccharides in litter reflect the climatic conditions of the last year,
      whereas delta18O values of the respective topsoils reflect the averaged climate
      signal of the last decades or even centuries. This demonstrates the high
      potential of the method for palaeoclimate reconstructions.

PMID- 19844973
TI  - Quantum dots-electrospray ionization mass spectrometry: 3-mercaptopropanic acid
      capped CdS quantum dots as accelerating and enrichment probes for microwave
      tryptic digestion of proteins.

PMID- 19844974
TI  - Facile synthesis of 4-mercaptophenylboronic acid functionalized gold
      nanoparticles for selective enrichment of glycopeptides.
AB  - In the work, 4-mercaptophenylboronic acid (4-MPBA)-functionalized gold
      nanoparticles were synthesized via a facile approach. At first, gold
      nanoparticles (about 50 nm) were prepared by a simple and convenient hydrothermal
      method based on a polyol process. Then, gold nanoparticles were modified with 4
      MPBA by the well-known reaction of Au with the thiol groups. The MPBA
      functionalized gold nanoparticles were characterized by Fourier transform
      infrared spectra and UV/Vis adsorption spectra. Due to the fact that the boronic
      acid group on the surface of 4-MPBA-modified gold particles can form tight yet
      reversible covalent bonds with glycopeptides containing cis-1,2-diols groups, the
      MPBA-modified gold nanoparticles were successfully applied to selective
      enrichment of glycopeptides. Isolation and enrichment of glycopeptides in a
      standard protein (asialofetuin and horseradish peroxidase) digestion and a
      complex sample were performed using MPBA-modified gold nanoparticles, followed by
      matrix-assisted laser desorption/ionization quadruple ion trap time-of-flight
      (MALDI-QIT-TOF) mass spectrometric analysis. The experimental results
      demonstrated that MPBA-modified gold nanoparticles synthesized by the facile
      approach have the powerful potential for selective enrichment of glycopeptides,
      and can be an alternative tool in glycoproteomics.

PMID- 19844975
TI  - Eating-disordered behavior in Australian and Singaporean women: a comparative
      study.
AB  - OBJECTIVE AND METHOD: We used the Eating Disorder Examination Questionnaire (EDE
      Q) to compare the specific eating disorder psychopathology of young adult women
      in Australia (n = 339) and Singapore (n = 164). All participants completed a
      brief questionnaire that included the EDE-Q, basic socio-demographic information,
      and self-reported height and weight. RESULTS: Overall levels of eating disorder
      psychopathology, as measured by the EDE-Q global score, were very similar. There
      were also no differences between groups on the EDE-Q subscales. However, analysis
      at the item level indicated that Singaporean women were more fearful of losing
      control over their eating, more fearful of gaining weight or becoming fat, and
      more anxious at the prospect of regularly weighing themselves, than Australian
      women. Singaporean women were also more likely to report binge eating and
      laxative misuse, whereas excessive exercise was more common among Australian
      women. The findings were unaltered when between-group differences in body weight
      were statistically controlled. DISCUSSION: The findings provide further evidence
      that levels of eating disorder psychopathology in some Asian countries may be as
      high as, if not higher than, those of Western nations. Potentially important
      differences between different cultural groups may be obscured when the assessment
      of eating disorder psychopathology is confined to summary-type measures.

PMID- 19844976
TI  - Soluble ions more than particulate cobalt-alloy implant debris induce monocyte
      costimulatory molecule expression and release of proinflammatory cytokines
      critical to metal-induced lymphocyte reactivity.
AB  - Aseptic osteolysis has been associated with excessive immune reactivity to
      particulate implant debris; however, innate and adaptive immune mechanisms that
      underlie implant debris reactivity remain incompletely understood. Although
      particulate debris has been implicated as the major type of implant debris
      mediating macrophage-induced osteolysis, the degree to which metal ions affect a
      proinflammatory response (if at all) remains unknown. We hypothesized that both
      soluble and particulate metal implant debris will induce proinflammatory
      responses in human monocytes resulting in cytokine production and elevated
      expression of T cell costimulatory molecules, facilitating adaptive immune
      responses. We tested this hypothesis by characterizing the response of a human
      monocyte cell line (THP-1), isolated primary human monocytes and PBMCs challenged
      with Co-Cr-Mo alloy particles and soluble cobalt, chromium, molybdenum, and
      nickel ions. Our results indicate that soluble cobalt, nickel, and molybdenum can
      induce monocyte up-regulation of T cell costimulatory molecules (CD80, CD86, ICAM
      1) in human monocytes/macrophages. Furthermore, cobalt, molybdenum ions, and Co
      Cr-Mo alloy particles similarly induce elevated secretion of IL-1beta, TNFalpha,
      and IL-6. Antibody blockade of CD80 and CD86, crucial secondary molecules for
      adaptive responses, abrogated lymphocyte reactivity to metal challenge in metal
      reactive subjects. Also the addition of IL-1 receptor antagonist (IL-1ra), (which
      indirectly blocks pro-IL-1beta and thus IL-1beta release), significantly reduced
      lymphocyte reactivity in metal-reactive subjects. Thus, both soluble and
      particulate metal implant debris induce monocyte/macrophage proinflammatory
      responses that are metal and individual specific. This suggests metal-induced up
      regulation of costimulatory molecules and proinflammatory cytokine production is
      necessary to induce lymphocyte activation/proliferation to metal implant debris.

PMID- 19844977
TI  - Oligomerization of adenosin-5'-O-ylmethylphosphonate, an isopolar AMP analogue:
      evaluation of the route to short oligoadenylates.
AB  - In an attempt to prepare a library of short oligoadenylate analogues featuring
      both the enzyme-stable internucleotide linkage and the 5'-O-methylphosphonate
      moiety and thus obtain a pool of potential RNase L agonists/antagonists, we
      studied the spontaneous polycondensation of the adenosin-5'-O-ylmethylphosphonic
      acid (p(c)A), an isopolar AMP analogue, and its imidazolide derivatives employing
      N,N'-dicyclohexylcarbodiimide under nonaqueous conditions and uranyl ions under
      aqueous conditions, respectively. The RP LC-MS analyses of the reaction mixtures
      per se, and those obtained after the periodate treatment, along with analyses and
      separations by capillary zone electrophoresis, allowed us to characterize major
      linear and cyclic oligoadenylates obtained. The structure of selected compounds
      was supported, after their isolation, by NMR spectroscopy. Ab initio calculation
      of the model structures simulating the AMP-imidazolide and p(c)A-imidazolide
      offered the explanation why the latter compound exerted, in contrast to AMP
      imidazolide, a very low stability in aqueous solutions.

PMID- 19844979
TI  - Do osmoregulators have lower capacity of muscle water regulation than
      osmoconformers? A study on decapod crustaceans.
AB  - Decapod crustaceans occupy various aquatic habitats. In freshwater they are
      osmoregulators, while marine species are typically osmoconformers. Freshwater
      crustaceans are derived from marine ancestors. The hypothesis tested here was
      that osmoregulators, which can rely on salt transport by interface epithelia to
      prevent extracellular disturbance, would have a lower capacity of tissue water
      regulation when compared with osmoconformers. Four species of decapod crustaceans
      (the marine osmoconformer crab Hepatus pudibundus, and three osmoregulators of
      different habitats) have been exposed in vivo to a salinity challenge, for up to
      24 hr. Osmoregulators were: the estuarine shrimp Palaemon pandaliformis, the
      diadromous freshwater shrimp Macrobrachium acanthurus, and the hololimnetic red
      crab Dilocarcinus pagei. H. pudibundus displayed hemolymph dilution already after
      0.5 hr in 25 per thousand, reaching approximately 30% reduction in osmolality,
      but its muscle degree of hydration did not increase. To make the different in
      vivo salinity challenges directly comparable, the ratio between the maximum
      change in muscle hydration with respect to the control value measured for the
      species and the maximum change in hemolymph osmolality was calculated (x 1,000):
      H. pudibundus (25 per thousand, 8.1% kg H(2)O/mOsm x 10(3))>P. pandaliformis (2
      per thousand, 9.2)>M. acanthurus (30 per thousand, 12.6)>P. pandaliformis (35 per
      thousand, 16.7)>D. pagei (7 per thousand, 60.4). Muscle slices submitted in vitro
      to a 30% osmotic challenge confirmed in vivo results. Thus, the
      estuarine/freshwater osmoregulators displayed a lower capacity to hold muscle
      tissue water than the marine osmoconformer, despite undergoing narrower
      variations in hemolymph osmolality.

PMID- 19844978
TI  - Distribution and axonal projections of neurons coexpressing thyrotropin-releasing
      hormone and urocortin 3 in the rat brain.
AB  - Thyrotropin-releasing hormone (TRH) decreases food intake when administered
      intracerebroventricularly or into the ventromedial hypothalamus. However, it is
      unknown which population of TRH neurons exerts this anorexigenic function. In the
      rostral perifornical area, the pattern of TRH-expressing neurons is reminiscent
      of the distribution of neurons expressing urocortin3 (Ucn3) that also inhibits
      feeding when injected into the hypothalamic ventromedial nucleus (VMN). Since
      colocalization of TRH and Ucn3 may help to identify feeding-related TRH neurons,
      the putative coexpression of the two peptides was examined using fluorescent in
      situ hybridization combined with immunofluorescence. Almost all (95.5 +/- 0.2%)
      Ucn3-immunoreactive neurons in the perifornical area expressed pro-TRH mRNA,
      while 50.2 +/- 1.6% Ucn3 neurons were double-labeled in the bed nucleus of the
      stria terminalis (BNST). Only a few Ucn3/pro-TRH neurons were found outside these
      two areas. The distribution of axons containing both Ucn3 and TRH was examined by
      dual immunofluorescence. Ucn3/TRH fibers heavily innervated the VMN. In addition,
      high densities of double-labeled axons were observed in the lateral septal
      nucleus, posterior division of the BNST, medial amygdaloid nucleus,
      amygdalohippocampal area, and ventral hippocampus, forebrain areas associated
      with psychological stress and anxiety. We conclude that Ucn3 and TRH are
      coexpressed in a discrete, continuous population of neurons in the perifornical
      area and BNST, making Ucn3 a neurochemical marker to define a distinct subset of
      TRH neurons. The distribution of their axons suggests that Ucn3/TRH neurons may
      coordinate feeding and behavioral responses to stressful stimuli.

PMID- 19844980
TI  - Quantum-dots-based fluoroimmunoassay for the rapid and sensitive detection of
      avian influenza virus subtype H5N1.
AB  - The continuous spread of highly pathogenic avian influenza virus (AIV) subtype
      H5N1 is threatening the poultry industry and human health worldwide. Rapid and
      sensitive diagnostic methods are required for the H5N1 surveillance. In this
      study, the fluorescent (FL) probe of CdTe quantum dots (QDs) was designed using
      covalently linked rabbit anti-AIV H5N1 antibody. Based on these QD-antibody
      conjugates, a novel sandwich FL-linked immunosorbent assay (sFLISA) was developed
      for H5N1 viral antigen detection. The sFLISA allowed for H5N1 viral antigen
      determination in a linear range of 8.0 * 10(-3) to 5.1 * 10(-1)  MUg mL(-1) with
      the limit of detection (LOD) of 1.5 * 10(-4)  MUg mL(-1) . In comparison with
      virus isolation for 103 clinic samples, the sensitivity and specificity of sFLISA
      were found to be 93.6 and 91.1% respectively. The sFLISA supplied a novel
      approach to rapid and sensitive detection of AIV subtype H5N1 and showed great
      potential for biological applications in immunoassays.

PMID- 19844981
TI  - Photo-mechanical effect in luminescent polymeric materials.
AB  - The photomechanical effect was found for the first time in a polymer composition
      on the basis of polymethylmethacrylate with embedded molecules of the luminophor
      dibenzoylmethanate of boron difluoride incapable of undergoing photochemical
      isomerization, unlike other compounds. A thermal mechanism of photochemical
      displacement was suggested.

PMID- 19844982
TI  - Comprehensive two-dimensional gas chromatography-mass spectrometry analysis of
      volatile constituents in Thai vetiver root oils obtained by using different
      extraction methods.
AB  - INTRODUCTION: Vetiver root oil is known as one of the finest fixatives used in
      perfumery. This highly complex oil contains more than 200 components, which are
      mainly sesquiterpene hydrocarbons and their oxygenated derivatives. Since
      conventional GC-MS has limitation in terms of separation efficiency, the
      comprehensive two-dimensional GC-MS (GC x GC-MS) was proposed in this study as an
      alternative technique for the analysis of vetiver oil constituents. OBJECTIVE: To
      evaluate efficiency of the hyphenated GC x GC-MS technique in terms of separation
      power and sensitivity prior to identification and quantitation of the volatile
      constituents in a variety of vetiver root oil samples. METHODOLOGY. Dried roots
      of Vetiveria zizanioides were subjected to extraction using various conditions of
      four different methods; simultaneous steam distillation, supercritical fluid,
      microwave-assisted, and Soxhlet extraction. Volatile components in all vetiver
      root oil samples were separated and identified by GC-MS and GC x GC-MS. The
      relative contents of volatile constituents in each vetiver oil sample were
      calculated using the peak volume normalization method. RESULTS: Different
      techniques of extraction had diverse effects on yield, physical and chemical
      properties of the vetiver root oils obtained. Overall, 64 volatile constituents
      were identified by GC-MS. Among the 245 well-resolved individual components
      obtained by GC x GC-MS, the additional identification of 43 more volatiles was
      achieved. CONCLUSION: In comparison with GC-MS, GC x GC-MS showed greater ability
      to differentiate the quality of essential oils obtained from diverse extraction
      conditions in terms of their volatile compositions and contents.

PMID- 19844983
TI  - Burkitt lymphoma versus diffuse large B-cell lymphoma: a practical approach.
AB  - Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO)
      classification of lymphoid tumours as an 'aggressive B-cell non-Hodgkin's
      lymphoma', characterized by a high degree of proliferation of the malignant cells
      and deregulation of the c-MYC gene. The main diagnostic challenge in BL is to
      distinguish it from diffuse large B-cell lymphoma (DLBCL). While in children BL
      and DLBCL types probably do not differ clinically, and the differential diagnosis
      between BL and DLBCL may theoretically appear clear-cut, in adults daily practice
      shows the existence of cases that have morphological features, immunophenotypic
      and cytogenetics intermediate between DLBCL and BL, and cannot be classified with
      certainty in these categories. Distinguishing between BL and DLBCL is critical,
      as the two diseases require different management. This review summarizes the
      current practical approach, including the use of a large panel of antibodies, and
      cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL
      and the provisional category of 'B-cell lymphoma, unclassifiable, with features
      intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma', now
      listed in the updated WHO classification.

PMID- 19844984
TI  - Bite force and performance in the durophagous bonnethead shark, Sphyrna tiburo.
AB  - Bite force, a measure of performance, can be used to link anatomical form and
      function. Earlier studies have shown bite force to have a significant influence
      on dietary constraints and ontogenetic shifts in resource utilization. The
      bonnethead shark, Sphyrna tiburo, is a durophagous member of the family
      Sphyrnidae. Its diet in South Florida waters consists almost entirely of blue
      crabs, which are crushed or ingested whole. This abundant coastal predator's
      feeding mechanism is specialized for the consumption of hard prey, including a
      modified biting pattern and molariform teeth. The goals of this research were to
      (1) characterize the mechanical function of the feeding mechanism of S. tiburo
      through biomechanical modeling of biting and in vivo bite force measurements; (2)
      compare the bite force of S. tiburo with those of other fishes; and (3) identify
      functional constraints on prey capture by comparing the bite force of S. tiburo
      with the fracture properties of its primary prey item, blue crabs. Maximum
      theoretical bite force ranged from 25.7 N anteriorly to 107.9 N posteriorly. S.
      tiburo has the second lowest mass specific bite force for any fish studied to
      date, and its posterior mechanical advantage of 0.88 is lower than other
      durophagous chondrichthyans, indicating that this independent evolutionary
      acquisition of durophagy was not accompanied by the associated morphological
      changes found in other durophagous cartilaginous fishes. Blue crab fracture
      forces (30.0-490.0 N) range well above the maximum bite force of S. tiburo,
      suggesting that prey material properties functionally constrain dietary ecology
      to some degree.

PMID- 19844985
TI  - Expression of CD117 by proerythroblasts.

PMID- 19844986
TI  - Prodromal myeloproliferative neoplasms: the 2008 WHO classification.
AB  - The concept of prodromal chronic myeloproliferative neoplasms has been endorsed
      by the WHO classification implicating a stepwise evolution of disease. Histology
      of the bone marrow (BM) and borderline to mildly expressed clinical features play
      a pivotal role for diagnosing prefibrotic-early primary myelofibrosis. By
      lowering the platelet count for essential thrombocythemia and regarding BM
      morphology, early manifestations are tackled. Pre-polycythemic stages of
      polycythemia vera with a low hemoglobin level at onset are diagnosed by positive
      JAK2V617F mutation status, a low erythropoietin value, and characteristic BM
      features. The revised WHO classification incorporates hematological,
      morphological, and molecular-genetic parameters to generate a consensus-based
      working diagnosis.

PMID- 19844987
TI  - Erythrocytapheresis in the prevention of recurrent myocardial infarction in
      sickle cell disease.

PMID- 19844988
TI  - Management of hematological malignancies during pregnancy.
AB  - The management of hematological malignancies during pregnancy is a challenging
      endeavor, which not only requires technical skills and knowledge by the
      clinicians but also requires sound clinical judgment and compassion, keeping in
      mind the patient and family preferences and, ultimately, the wellbeing of the
      neonate. The incidence of hematological malignancies during pregnancy is rare,
      ranging from 1 in 1,000 to 1 in 10,000 deliveries, impeding the design and
      execution of large prospective studies. The purpose of this review is to evaluate
      the limited existing data and make useful suggestions in the management of acute
      and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, plasma cell myeloma,
      and other hematological malignancies, such as myelodysplastic syndromes and hairy
      cell leukemia, during pregnancy.

PMID- 19844989
TI  - Successful combination treatment of clofarabine, cytarabine, and gemtuzumab
      ozogamicin in adult refractory B-acute lymphoblastic leukemia.

PMID- 19844990
TI  - Identification of molecular targets associated with transformed diffuse large B
      cell lymphoma using highly purified tumor cells.
AB  - Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse
      large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified
      for predictive or early diagnosis. Gene expression analyses have identified genes
      changing on transformation but have failed to be reproducible in different
      studies, reflecting the heterogeneity within the tumor tissue and between tumor
      samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays
      were performed, using flow cytometry sorted tumor cells derived from FL and
      transformed DLBCL. To identify molecular targets associated with the
      transformation, subsequent immunohistochemistry (IHC) analyses of the
      corresponding proteins were performed. Using highly purified cells, this study
      identified 163 genes, which were significantly deregulated during the
      transformation in a majority of cases. Among the upregulated transcripts, 13
      genes were selected for validation using IHC, based on the availability of
      commercial antibodies, and galectin-3 and NEK2 proteins specifically identify
      DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells
      through cell sorting, thereby reducing the heterogeneity due to infiltrating
      cells, it was possible to identify distinct differences between tumor entities
      rather than variations due to cellular composition. Galectin-3 and NEK2 both
      identified a subgroup of DLBCL-tr, and the function of these protein markers also
      suggests a biological role in the transformation process.

PMID- 19844991
TI  - Gonadotropin-inhibitory hormone identification, cDNA cloning, and distribution in
      rhesus macaque brain.
AB  - Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that
      modulates the reproductive physiology of birds and mammals by inhibiting
      gonadotropin secretion from the anterior pituitary gland. GnIH can also directly
      inhibit reproductive behaviors, possibly via action within the brain.
      Identification of the distribution of GnIH neurons and fibers may provide us with
      clues to how the brain controls reproductive activities of the animal. Here, we
      characterized the location and connectivity of GnIH neurons in the rhesus macaque
      (Macaca mulatta) brain. We determined the macaque GnIH precursor mRNA, and
      further identified a mature GnIH peptide (SGRNMEVSLVRQVLNLPQRF-NH(2)) by mass
      spectrometry combined with immunoaffinity purification. The majority of GnIH
      precursor mRNA-positive and GnIH-immunoreactive (GnIH-ir) cell bodies were
      localized in the intermediate periventricular nucleus (IPe) in the hypothalamus,
      as determined by in situ hybridization and immunocytochemistry, respectively.
      Abundant GnIH-ir fibers were observed in the nucleus of the stria terminalis in
      the telencephalon; habenular nucleus, paraventricular nucleus of the thalamus,
      preoptic area, paraventricular nucleus of the hypothalamus, IPe, arcuate nucleus
      of hypothalamus, median eminence and dorsal hypothalamic area in the
      diencephalon; medial region of the superior colliculus, central gray substance of
      the midbrain and dorsal raphe nucleus in the midbrain; and parabrachial nucleus
      in the pons. GnIH-ir fibers were observed in close proximity to gonadotropin
      releasing hormone-I, dopamine, beta-endorphin, and gonadotropin-releasing hormone
      II neurons in the preoptic area, IPe, arcuate nucleus of hypothalamus, and
      central gray substance of midbrain, respectively. GnIH neurons might thus
      regulate several neural systems in addition to pituitary gonadotropin release.

PMID- 19844992
TI  - Localization of relaxin-3 in brain of Macaca fascicularis: identification of a
      nucleus incertus in primate.
AB  - Relaxin-3 (RLN3) is a highly conserved, ancestral member of the insulin/relaxin
      peptide family. RLN3 mRNA is highly expressed in rat, mouse, and human brain and
      molecular genetic and pharmacological studies suggest that RLN3 is the cognate
      ligand for the relaxin family peptide-3 receptor (RXFP3). The distribution of
      RLN3/RXFP3 networks has been determined in rat and mouse brain, but not in higher
      species. In this study we describe the distribution of RLN3 neurons in the brain
      of macaque (Macaca fascicularis) using in situ hybridization histochemistry and
      immunohistochemistry. RLN3 mRNA and high levels of RLN3-like immunoreactivity (
      LI) were observed in neurons within a ventromedial region of the central gray of
      the pons and medulla that appears to represent the primate analog of the nucleus
      incertus (NI) described in lower species. Nerve fibers and terminals containing
      RLN3-LI were observed throughout brain regions identical to those known to
      receive afferents from the NI in the rat, including the septum, hippocampus,
      entorhinal cortex, lateral, dorsomedial and ventromedial hypothalamus,
      supramammillary and interpeduncular nuclei, anterodorsal, paraventricular and
      reuniens thalamic nuclei, lateral habenula, central gray, and dorsal raphe,
      solitary tract, and ambiguus nuclei. Experimental studies in the rat strongly
      implicate a role of this neuropeptide-receptor system in arousal, feeding, and
      metabolism, learning and memory, and central responses to psychological
      stressors. These new anatomical findings support the proposition that the RLN3
      system is similarly involved in the integration and modulation of behavioral
      activation and arousal and responses to stress in nonhuman primates and humans.

PMID- 19844993
TI  - Two-dimensional crystals of carboxysome shell proteins recapitulate the hexagonal
      packing of three-dimensional crystals.
AB  - Bacterial microcompartments (BMCs) are large intracellular bodies that serve as
      simple organelles in many bacteria. They are proteinaceous structures composed of
      key enzymes encapsulated by a polyhedral protein shell. In previous studies, the
      organization of these large shells has been inferred from the conserved packing
      of the component shell proteins in two-dimensional (2D) layers within the context
      of three-dimensional (3D) crystals. Here, we show that well-ordered, 2D crystals
      of carboxysome shell proteins assemble spontaneously when His-tagged proteins
      bind to a monolayer of nickelated lipid molecules at an air-water interface. The
      molecular packing within the 2D crystals recapitulates the layered hexagonal
      sheets observed in 3D crystals. The results reinforce current models for the
      molecular design of BMC shells.

PMID- 19844994
TI  - The dual dopamine-glutamate phenotype of growing mesencephalic neurons regresses
      in mature rat brain.
AB  - Coexpression of tyrosine hydroxylase (TH) and vesicular glutamate transporter 2
      (VGLUT2) mRNAs in the ventral tegmental area (VTA) and colocalization of these
      proteins in axon terminals of the nucleus accumbens (nAcb) have recently been
      demonstrated in immature (15-day-old) rat. After neonatal 6-hydroxydopamine (6
      OHDA) lesion, the proportion of VTA neurons expressing both mRNAs and of nAcb
      terminals displaying the two proteins was enhanced. To determine the fate of this
      dual phenotype in adults, double in situ hybridization and dual immunolabeling
      for TH and VGLUT2 were performed in 90-day-old rats subjected or not to the
      neonatal 6-OHDA lesion. Very few neurons expressed both mRNAs in the VTA and
      substantia nigra (SN) of P90 rats, even after neonatal 6-OHDA. Dually
      immunolabeled terminals were no longer found in the nAcb of normal P90 rats and
      were exceedingly rare in the nAcb of 6-OHDA-lesioned rats, although they had
      represented 28% and 37% of all TH terminals at P15. Similarly, 17% of all TH
      terminals in normal neostriatum and 46% in the dopamine neoinnervation of SN in 6
      OHDA-lesioned rats were also immunoreactive for VGLUT2 at P15, but none at P90.
      In these three regions, all dually labeled terminals made synapse, in
      contradistinction to those immunolabeled for only TH or VGLUT2 at P15. These
      results suggest a regression of the VGLUT2 phenotype of dopamine neurons with
      age, following normal development, lesion, or sprouting after injury, and a role
      for glutamate in the establishment of synapses by these neurons.

PMID- 19844996
TI  - Expression profile of PTPIP51 in mouse brain.
AB  - This study demonstrates the expression of the novel protein protein tyrosine
      phophatase-interacting protein 51 (PTPIP51) in mammalian brain tissue. Serial
      sections of the whole adult mouse brain were analyzed for PTPIP51 protein and
      mRNA by immunohistochemistry, immunoblotting, RT-PCR, and in situ hybridization.
      Recent investigations by Yu et al. (2008) describe PTPIP51 as being capable of
      activating Raf-1, thereby modulating the MAPK pathway. The role of Raf-1, as well
      as of 14-3-3, in neurological disorders is well established. PTPIP51 expression
      was confined to neurons in the following structures: the piriform cortex and
      their connections to the anterior commissure, nucleus accumbens, paraventricular
      and supraoptical nuclei, neurohypophysis, superior colliculus, genu of facialis
      nerve, spinal trigeminal tract, inferior cerebellar peduncle, and cerebellum. In
      the cerebellum, a subpopulation of Purkinje cells and their dendrites was
      strongly PTPIP51 positive. Moreover, PTPIP51 was found to be colocalized with
      vasopressin and its transport protein neurophysin II in the neuroendocrine nuclei
      and their connections to the neurohypophysis. The data presented here suggest a
      role of PTPIP51 in neuronal homeostasis, axonal growth, and transport.

PMID- 19844997
TI  - Neuronal expression of Cd36, Cd44, and Cd83 antigen transcripts maps to distinct
      and specific murine brain circuits.
AB  - Cells recruited by the innate immune response rely on surface-expressed molecules
      in order to receive signals from the local environment and to perform
      phagocytosis, cell adhesion, and others processes linked to host defense.
      Hundreds of surface antigens designated through a cluster of differentiation (CD)
      number have been used to identify particular populations of leukocytes.
      Surprisingly, we verified that the genes that encode Cd36 and Cd83 are
      constitutively expressed in specific neuronal cells. For instance, Cd36 mRNA is
      expressed in some regions related to circuitry involved in pheromone responses
      and reproductive behavior. Cd44 expression, reanalyzed and detailed here, is
      associated with the laminar formation and midline thalamic nuclei in addition to
      striatum, extended amygdala, and a few hypothalamic, cortical, and hippocampal
      regions. A systemic immune challenge was able to increase Cd44 expression quickly
      in the area postrema and motor nucleus of the vagus but not in regions presenting
      expressive constitutive expression. In contrast to Cd36 and Cd44, Cd83 message
      was widely distributed from the olfactory bulb to the brain stem reticular
      formation, sparing the striatopallidum, olivary region, and cerebellum. Its
      pattern of expression nevertheless remained strongly associated with
      hypothalamic, thalamic, and hindbrain nuclei. Unlike the other transcripts, Cd83
      mRNA was rapidly modulated by restraint stress. Our results indicate that these
      molecules might play a role in specific neural circuits and present functions
      other than those attributed to leukocyte biology. The data also suggest that
      these surface proteins, or their associated mRNA, could be used to label neurons
      in specific circuits/regions.

PMID- 19844998
TI  - Optimal foraging on the roof of the world: Himalayan langurs and the classical
      prey model.
AB  - Optimal foraging theory has only been sporadically applied to nonhuman primates.
      The classical prey model, modified for patch choice, predicts a sliding
      "profitability threshold" for dropping patch types from the diet, preference for
      profitable foods, dietary niche breadth reduction as encounter rates increase,
      and that exploitation of a patch type is unrelated to its own abundance. We
      present results from a 1-year study testing these predictions with Himalayan
      langurs (Semnopithecus entellus) at Langtang National Park, Nepal. Behavioral
      data included continuous recording of feeding bouts and between-patch travel
      times. Encounter rates were estimated for 55 food types, which were analyzed for
      crude protein, lipid, free simple sugar, and fibers. Patch types were entered
      into the prey model algorithm for eight seasonal time periods and differing age
      sex classes and nutritional currencies. Although the model consistently
      underestimated diet breadth, the majority of nonpredicted patch types represented
      rare foods. Profitability was positively related to annual/seasonal dietary
      contribution by organic matter estimates, whereas time estimates provided weaker
      relationships. Patch types utilized did not decrease with increasing encounter
      rates involving profitable foods, although low-ranking foods available year-round
      were taken predominantly when high-ranking foods were scarce. High-ranking foods
      were taken in close relation to encounter rates, while low-ranking foods were
      not. The utilization of an energetic currency generally resulted in closest
      conformation to model predictions, and it performed best when assumptions were
      most closely approximated. These results suggest that even simple models from
      foraging theory can provide a useful framework for the study of primate feeding
      behavior.

PMID- 19844999
TI  - Synchrony between growth and reproductive patterns in human females: Early
      investment in growth among Pume foragers.
AB  - Life history is an important framework for understanding many aspects of ontogeny
      and reproduction relative to fitness outcomes. Because growth is a key influence
      on the timing of reproductive maturity and age at first birth is a critical
      demographic variable predicting lifetime fertility, it raises questions about the
      synchrony of growth and reproductive strategies. Among the Pume, a group of South
      American foragers, young women give birth to their first child on average at age
      15.5. Previous research showed that this early age at first birth maximizes
      surviving fertility under conditions of high infant mortality. In this study we
      evaluate Pume growth data to test the expectation that if early reproduction is
      advantageous, then girls should have a developmental trajectory that best
      prepares them for young childbearing. Analyses show that comparatively Pume girls
      invest in skeletal growth early, enter puberty having achieved a greater
      proportion of adult body size and grow at low velocities during adolescence. For
      early reproducers growing up in a food-limited environment, a precocious
      investment in growth is advantageous because juveniles have no chance of
      pregnancy and it occurs before the onset of the competing metabolic demands of
      final reproductive maturation and childbearing. Documenting growth patterns under
      preindustrial energetic and demographic conditions expands the range of
      developmental variation not otherwise captured by normative growth standards and
      contributes to research on human phenotypic plasticity in diverse environments.

PMID- 19845000
TI  - Nigrostriatal dysfunction in homozygous and heterozygous parkin gene carriers: an
      18F-dopa PET progression study.
AB  - Little is known about the rate of progression of striatal dysfunction in subjects
      with parkin-linked parkinsonism. Being a heterozygous parkin gene carrier may
      confer susceptibility to Parkinson's disease (PD). In a previous (18)F-dopa PET
      study, we reported that 69% of carriers of a single parkin mutation showed
      subclinical loss of putamen dopaminergic function. Using serial (18)F-dopa PET,
      the present longitudinal study addresses rates of progression of nigrostriatal
      dysfunction in both compound heterozygous (parkin-linked parkinsonism) and single
      heterozygous parkin gene carriers. Three symptomatic patients who were compound
      heterozygotes for parkin gene mutations and six asymptomatic heterozygous
      carriers were clinically assessed and had (18)F-dopa PET at baseline and again
      after 5 years. The patients with symptomatic parkin showed a mean 0.5% annual
      reduction in putamen (18)F-dopa uptake over 5 years while caudate (18)F-dopa
      uptake declined by a mean annual rate of 2 %. The asymptomatic heterozygote gene
      carriers showed a mean 0.56% annual reduction in putamen and 0.62 % annual
      reduction in caudate (18)F-dopa uptake. Neurological examination at both baseline
      and follow-up showed no evidence of parkinsonism. Loss of nigrostriatal
      dysfunction in parkin-linked parkinsonism occurs at a very slow rate compared to
      the 9-12% annual loss of putamen (18)F-dopa uptake reported for idiopathic PD.
      Although subclinical reductions of striatal (18)F-dopa uptake are common in
      carriers of a single parkin mutation their slow rate of progression suggests that
      few if any of these will develop clinical parkinsonism.

PMID- 19845001
TI  - Triple light chain antibodies: factors that influence its formation in cell
      culture.
AB  - THIOMABs are recombinant antibodies engineered with reactive cysteines, which can
      be covalently conjugated to drugs of interest to generate targeted therapeutics.
      During the analysis of THIOMABs secreted by stably transfected Chinese Hamster
      Ovary (CHO) cells, we discovered the existence of a new species--Triple Light
      Chain Antibody (3LC). This 3LC species is the product of a disulfide bond formed
      between an extra light chain and one of the engineered cysteines on the THIOMAB.
      We characterized the 3LC by size exclusion chromatography, mass spectrometry, and
      microchip electrophoresis. We also investigated the potential causes of 3LC
      formation during cell culture, focusing on the effects of free light chain (LC)
      polypeptide concentration, THIOMAB amino acid sequence, and glutathione (GSH)
      production. In studies covering 12 THIOMABs produced by 66 stable cell lines,
      increased free LC polypeptide expression--evaluated as the ratio of mRNA encoding
      for LC to the mRNA encoding for heavy chain (HC)--correlated with increased 3LC
      levels. The amino acid sequence of the THIOMAB molecule also impacted its
      susceptibility to 3LC formation: hydrophilic LC polypeptides showed elevated 3LC
      levels. Finally, increased GSH production--evaluated as the ratio of the cell
      specific production rate of GSH (q(GSH)) to the cell-specific production rate of
      THIOMAB (q(p))--corresponded to decreased 3LC levels. In time-lapse studies,
      changes in extracellular 3LC levels during cell culture corresponded to changes
      in mRNA LC/HC ratio and q(GSH)/q(p) ratio. In summary, we found that cell lines
      with low mRNA LC/HC ratio and high q(GSH)/q(p) ratio yielded the lowest levels of
      3LC. These findings provide us with factors to consider in selecting a cell line
      to produce THIOMABs with minimal levels of the 3LC impurity.

PMID- 19845002
TI  - A validated model of GAG deposition, cell distribution, and growth of tissue
      engineered cartilage cultured in a rotating bioreactor.
AB  - In this work a new phenomenological model of growth of cartilage tissue cultured
      in a rotating bioreactor is developed. It represents an advancement of a
      previously derived model of deposition of glycosaminoglycan (GAG) in engineered
      cartilage by (i) introduction of physiological mechanisms of proteoglycan
      accumulation in the extracellular matrix (ECM) as well as by correlating (ii)
      local cell densities and (iii) tissue growth to the ECM composition. In
      particular, previously established predictions and correlations of local oxygen
      concentrations and GAG synthesis rates are extended to distinguish cell secreted
      proteoglycan monomers free to diffuse in cell surroundings and outside from the
      engineered construct, from large aggrecan molecules, which are constrained within
      the ECM and practically immovable. The model includes kinetics of aggregation,
      that is, transformation of mobile GAG species into immobile aggregates as well as
      maintenance of the normal ECM composition after the physiological GAG
      concentration is reached by incorporation of a product inhibition term. The model
      also includes mechanisms of the temporal evolution of cell density distributions
      and tissue growth under in vitro conditions. After a short initial proliferation
      phase the total cell number in the construct remains constant, but the local cell
      distribution is leveled out by GAG accumulation and repulsion due to negative
      molecular charges. Furthermore, strong repulsive forces result in expansion of
      the local tissue elements observed macroscopically as tissue growth (i.e.,
      construct enlargement). The model is validated by comparison with experimental
      data of (i) GAG distribution and leakage, (ii) spatial-temporal distributions of
      cells, and (iii) tissue growth reported in previous works. Validation of the
      model predictive capability--against a selection of measured data that were not
      used to construct the model--suggests that the model successfully describes the
      interplay of several simultaneous processes carried out during in vitro cartilage
      tissue regeneration and indicates that this approach could also be attractive for
      application in other tissue engineering systems.

PMID- 19845003
TI  - Regioselective hydroxylation of daidzein using P450 (CYP105D7) from Streptomyces
      avermitilis MA4680.
AB  - Regiospecific 3'-hydroxylation reaction of daidzein was performed with CYP105D7
      from Streptomyces avermitilis MA4680 expressed in Escherichia coli. The apparent
      K(m) and k(cat) values of CYP105D7 for daidzein were 21.83 +/- 6.3 microM and
      15.01 +/- 0.6 min(-1) in the presence of 1 microM of CYP105D7, putidaredoxin
      (CamB) and putidaredoxin reductase (CamA), respectively. When CYP105D7 was
      expressed in S. avermitilis MA4680, its cytochrome P450 activity was confirmed by
      the CO-difference spectra at 450 nm using the whole cell extract. When the whole
      cell reaction for the 3'-hydroxylation reaction of daidzein was carried out with
      100 microM of daidzein in 100 mM of phosphate buffer (pH 7.5), the recombinant S.
      avermitilis grown in R2YE media overexpressing CYP105D7 and ferredoxin FdxH
      (SAV7470) showed a 3.6-fold higher conversion yield (24%) than the corresponding
      wild type cell (6.7%). In a 7 L (working volume 3 L) jar fermentor, the
      recombinants S. avermitilis grown in R2YE media produced 112.5 mg of 7,3',4'
      trihydroxyisoflavone (i.e., 29.5% conversion yield) from 381 mg of daidzein in 15
      h.

PMID- 19845004
TI  - The crystal structure of a TIR domain from Arabidopsis thaliana reveals a
      conserved helical region unique to plants.
AB  - Plants use a highly evolved immune system to exhibit defense response against
      microbial infections. The plant TIR domain, together with the nucleotide-binding
      (NB) domain and/or a LRR region, forms a type of molecule, named resistance (R)
      proteins, that interact with microbial effector proteins and elicit
      hypersensitive responses against infection. Here, we report the first crystal
      structure of a plant TIR domain from Arabidopsis thaliana (AtTIR) solved at a
      resolution of 2.0 A. The structure consists of five beta-strands forming a
      parallel beta-sheet at the core of the protein. The beta-strands are connected by
      a series of alpha-helices and the overall fold mimics closely that of other
      mammalian and bacterial TIR domains. However, the region of the alphaD-helix
      reveals significant differences when compared with other TIR structures,
      especially the alphaD3-helix that corresponds to an insertion only present in
      plant TIR domains. Available mutagenesis data suggest that several conserved and
      exposed residues in this region are involved in the plant TIR signaling function.

PMID- 19845005
TI  - An interdomain disulfide bridge links the NtA and first FS domain in agrin.
AB  - Agrin is a multidomain heparan sulfate proteoglycan involved in postsynaptic
      differentiation at the neuromuscular junction. Binding of agrin to synaptic basal
      lamina is mediated by the N-terminal agrin (NtA) domain. The NtA domain of agrin
      is followed by a tandem of nine follistatin-like (FS) domains forming a rod-like
      spacer to the laminin G-like domains of the molecule. Here we report that the
      most C-terminal cysteine residue of NtA (Cys123) forms an interdomain disulfide
      bond with the FOLN subdomain of the FS module. Remarkably, this single cysteine
      is flanked by Leu117 and Val124, which are two essential beta-branched amino
      acids forming the heterocomplex of NtA with the gamma 1 chain of laminin.
      Moreover, we show that this covalent linkage compensates for the seven amino acid
      residue splice insert at the very C-terminal helix H3 and causes a rigid
      interface between NtA and FS independent of the alternative mRNA splice event.
      These results suggest that the interdomain disulfide bond between the NtA and the
      first FS domain might be important for the proper folding of agrin.

PMID- 19845006
TI  - Giant somatosensory evoked potential in a patient with shaking TIA.

PMID- 19845007
TI  - Neurological symptoms in patients with biopsy proven celiac disease.
AB  - In celiac disease (CD), the gut is the typical manifestation site but atypical
      neurological presentations are thought to occur in 6 to 10% with cerebellar
      ataxia being the most frequent symptom. Most studies in this field are focused on
      patients under primary neurological care. To exclude such an observation bias,
      patients with biopsy proven celiac disease were screened for neurological
      disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age
      51 +/- 15 years, mean disease duration 8 +/- 11 years) were recruited through
      advertisements. All participants adhered to a gluten-free diet. Patients were
      interviewed following a standard questionnaire and examined clinically for
      neurological symptoms. Medical history revealed neurological disorders such as
      migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%),
      seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported
      of a history of psychiatric disease including depression, personality changes, or
      even psychosis. Physical examination yielded stance and gait problems in about
      one third of patients that could be attributed to afferent ataxia in 26%,
      vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features
      such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were
      infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle
      reflexes in 14%. Gait disturbances in CD do not only result from cerebellar
      ataxia but also from proprioceptive or vestibular impairment. Neurological
      problems may even develop despite strict adherence to a gluten-free diet.

PMID- 19845008
TI  - Unilateral periodic limb movements: is this a pointer for atypical presentation
      of corticobasal degeneration syndrome?--A case report.

PMID- 19845009
TI  - Opsoclonus myoclonus syndrome in the context of Salmonellosis.

PMID- 19845010
TI  - Paraneoplastic chorea associated with breast cancer.

PMID- 19845011
TI  - A validation exercise on the new consensus criteria for multiple system atrophy.
AB  - The revised (new) consensus clinical diagnostic criteria for multiple system
      atrophy (MSA) were published in 2008. To validate these criteria, we utilized the
      same cohort that we reported previously, which included 59 patients with a
      clinical diagnosis of MSA that was confirmed neuropathologically in 51 of them at
      the Queen Square Brain Bank for Neurological Disorders. At the first clinic
      visit, sensitivity with new consensus possible category was higher, and PPV
      marginally higher, than for clinical diagnosis and old consensus possible
      category. New consensus probable category showed marginally higher sensitivity
      than, and the same PPV as, old consensus probable category. At the last clinic
      visit, new consensus possible category had exactly the same sensitivity and only
      marginally higher PPV compared with old consensus possible category. New
      consensus probable category showed the same sensitivity and PPV as old consensus
      probable category. Our data indicate that in this case material the new consensus
      criteria for possible MSA could improve diagnostic accuracy at first neurological
      evaluation compared with the old consensus criteria. Prospective
      clinicopathological validation studies of the new consensus criteria,
      particularly incorporating in vivo structural and functional imaging results, are
      required to extend the current findings.

PMID- 19845012
TI  - Neck movement speed in cervical dystonia.
AB  - Clinical scales of patients with cervical dystonia do not rate neck movement
      velocity. We prospectively measured range of neck movements and movement
      velocities in 35 consecutive patients with cervical dystonia (CD) and 29 normal
      controls. Reduction of peak velocities in patients with CD was the most robust
      abnormality and was correlated to TWSTRS. Coupled movements out of attempted
      movement plane were increased in the patient group. Movement range was moderately
      though significantly reduced. We conclude that slowing of voluntary neck
      movements is a frequent and hitherto unrecognized feature in CD.

PMID- 19845013
TI  - Complex movement disorders in a sporadic Boucher-Neuhauser Syndrome: Phenotypic
      manifestations beyond the triad.

PMID- 19845014
TI  - Characterization of a biofilm membrane reactor and its prospects for fine
      chemical synthesis.
AB  - Biofilms are known to be robust biocatalysts. Conventionally, they have been
      mainly applied for wastewater treatment, however recent reports about their
      employment for chemical synthesis are increasingly attracting attention.
      Engineered Pseudomonas sp. strain VLB120 Delta C biofilm growing in a tubular
      membrane reactor was utilized for the continuous production of (S)-styrene oxide.
      A biofilm specific morphotype appeared in the effluent during cultivation,
      accounting for 60-80% of the total biofilm irrespective of inoculation conditions
      but with similar specific activities as the original morphotype. Mass transfer of
      the substrate styrene and the product styrene oxide was found to be dependent on
      the flow rate but was not limiting the epoxidation rate. Oxygen was identified as
      one of the main parameters influencing the biotransformation rate. Productivity
      was linearly dependent on the specific membrane area and on the tube wall
      thickness. On average volumetric productivities of 24 g L(aq) (-1) day(-1) with a
      maximum of 70 g L(aq) (-1) day(-1) and biomass concentrations of 45 g (BDW) L(aq)
      (-1) have been achieved over long continuous process periods (>or=50 days)
      without reactor downtimes.

PMID- 19845015
TI  - Expression of the diabetes-associated gene TCF7L2 in adult mouse brain.
AB  - Polymorphisms of the gene TCF7L2 (transcription factor 7-like 2) are strongly
      associated with the development and progression of type 2 diabetes. TCF7L2 is
      important in the development of peripheral organs such as adipocytes, pancreas,
      and the intestine. However, very little is known about its expression elsewhere.
      In this study we used in situ hybridization histochemistry to show that TCF7L2
      has a unique expression pattern in the mouse brain. TCF7L2 is expressed in two
      distinct populations. First, it is highly expressed in thalamic and tectal
      structures. Additionally, TCF7L2 mRNA is expressed at moderate to low levels in
      specific cells of the hypothalamus, preoptic nucleus, and circumventricular
      organs. Collectively, these patterns of expression suggest that TCF7L2 has
      distinct functions within the brain, with a general role in the development and
      maintenance of thalamic and midbrain neurons, and then a distinct role in
      autonomic homeostasis.

PMID- 19845016
TI  - Systematic engineering of phytochelatin synthesis and arsenic transport for
      enhanced arsenic accumulation in E. coli.
AB  - Phytochelatin (PC) is a naturally occurring peptide with high affinity towards
      arsenic (As). In this article, we demonstrated the systematic engineering of PC
      producing E. coli for As accumulation by addressing different bottlenecks in PC
      synthesis as well as As transport. Phytochelatin synthase from
      Schizosaccharomyces pombe (SpPCS) was expressed in E. coli resulting in 18 times
      higher As accumulation. PC production was further increased by co-expressing a
      feedback desensitized gamma-glutamylcysteine synthetase (GshI*), resulting in 30
      fold higher PC levels and additional 2-fold higher As accumulation. The
      significantly increased PC levels were exploited further by co-expressing an
      arsenic transporter GlpF, leading to an additional 1.5-fold higher As
      accumulation. These engineering steps were finally combined in an arsenic efflux
      deletion E. coli strain to achieve an arsenic accumulation level of 16.8
      micromol/g DCW, a 80-fold improvement when compared to a control strain not
      producing phytochelatins.

PMID- 19845017
TI  - Image segmentation and dynamic lineage analysis in single-cell fluorescence
      microscopy.
AB  - An increasingly common component of studies in synthetic and systems biology is
      analysis of dynamics of gene expression at the single-cell level, a context that
      is heavily dependent on the use of time-lapse movies. Extracting quantitative
      data on the single-cell temporal dynamics from such movies remains a major
      challenge. Here, we describe novel methods for automating key steps in the
      analysis of single-cell, fluorescent images-segmentation and lineage
      reconstruction-to recognize and track individual cells over time. The automated
      analysis iteratively combines a set of extended morphological methods for
      segmentation, and uses a neighborhood-based scoring method for frame-to-frame
      lineage linking. Our studies with bacteria, budding yeast and human cells,
      demonstrate the portability and usability of these methods, whether using phase,
      bright field or fluorescent images. These examples also demonstrate the utility
      of our integrated approach in facilitating analyses of engineered and natural
      cellular networks in diverse settings. The automated methods are implemented in
      freely available, open-source software.

PMID- 19845018
TI  - The importance of Foxp3 antibody and fixation/permeabilization buffer
      combinations in identifying CD4+CD25+Foxp3+ regulatory T cells.
AB  - Foxp3 is a key marker for CD4(+) regulatory T cells (T(regs)) and was used in
      developing a multiparameter flow cytometric panel to identify T(regs). Achieving
      reproducible staining and analysis first required optimization of Foxp3 staining.
      We present a comparative study of PCH101, 236A/E7, 3G3, 206D, 150D, and 259D/C7
      clones of anti-human-Foxp3 antibodies used in combination with five different
      fixation/permeabilization buffers. Staining for CD25, CD152, and CD127 was also
      compared between fixation/permeabilization treatments. Promising antibody/buffer
      combinations were tested in a panel of peripheral blood mononuclear cells from 10
      individuals, and then on fresh versus frozen cells from four individuals.
      Finally, different fluorochromes coupled to two representative antibodies were
      compared to optimize separation of Foxp3(+) from Foxp3(-) events. Foxp3 gates
      were set using two gating strategies based on CD127(+)CD25(-) "non-T(regs)" or
      based on isotype controls. For Foxp3 staining, the best conditions for
      fixation/permeabilization were obtained using the eBioscience Foxp3, Imgenex,
      BioLegend, and BD Foxp3 buffers. Comparing results from 10 subjects, 259D/C7,
      PCH101, 236A/E7, and 206D antibodies yielded statistically higher levels of Foxp3
      cells than those by 150D and 3G3 antibodies (mean = 6.9, 5.1, 4.7, and 3.7%
      compared with 1.7, and 0.3% of CD25(+)Foxp3(+) events within CD4(+) cells,
      respectively). Importantly, the "nonspecificity" of some antibodies observed with
      a Foxp3 gate based on isotype controls could be eliminated by setting the Foxp3
      gate on "non-T(regs)". Better separation of Foxp3(+) and Foxp3(-) populations was
      observed using the PCH101 clone coupled to Alexa647 compared with FITC or the
      259D/C7 clone coupled to PE compared with Alexa488 fluorochrome. Foxp3 staining
      can be highly variable and depends on the choice of antibody/buffer pair and the
      fluorochrome used. Selecting the correct population for setting the Foxp3 gate is
      critical to avoid including non-T(regs) in the Foxp3(+) gate. The experiments
      presented here will aid in optimization of flow cytometry staining panels to
      quantify T(reg) frequencies in humans.

PMID- 19845019
TI  - An efficient high-throughput flow cytometric method for estimating DNA ploidy
      level in plants.
AB  - We present an efficient high-throughput flow cytometric method that builds on
      previously published methods and permits rapid ploidy discrimination in plants.
      By using Brassica napus L. microspore-derived plants as an example, we describe
      how 192 leaf tissue samples may be processed and analyzed comfortably by one
      operator in 6 h from tissue sampling to ploidy determination. The technique
      involves placing young leaf samples in two 96-well racks, using a bead-beating
      procedure to release nuclei into a lysis solution, filtering the samples on 96
      well filter plates, staining with propidium iodide, and then rapidly estimating
      DNA ploidy using a plate loader on a BD FACS-Canto II flow cytometer. Throughout
      the sample preparation process, multichannel pipetting allows faster and less
      error-prone sample handling. In two 96-well plates of samples, the histogram
      peaks of DNA content from flow cytometry were wellresolved in 189 of 192 samples
      tested (98.4%), with CV values ranging from 2.98% to 6.20% with an average CV of
      4.35% (SD = 0.68%). This new method is useful in doubled haploid plant breeding
      programs where early discrimination of haploid and doubled haploid (i.e.,
      diploid) plantlets can confer significantly improved operational efficiencies. We
      discuss how this method could be further refined including adapting the method to
      robotic sample processing.

PMID- 19845020
TI  - Coaxial electrohydrodynamic spraying of plasmid DNA/polyethylenimine (PEI)
      polyplexes for enhanced nonviral gene delivery.
AB  - DNA/polyethylenimine (PEI) polyplexes are an important class of nonviral vectors.
      Although the conventional preparation method, bulk mixing, is straightforward,
      the formation of the DNA/PEI polyplexes is not well controlled. This work
      explores coaxial electrohydrodynamic spraying (EHDS) as a novel, alternative
      method to produce DNA/PEI polyplexes in a more controlled manner. Both pGFP/PEI
      and pSEAP/PEI polyplexes were produced by EHDS with a coaxial needle setup. The
      size of the polyplexes was determined using dynamic light scattering, and their
      ability to transfect NIH 3T3 cells was observed by using an inverted fluorescence
      microscope (pGFP) or quantified by measuring the activity level of alkaline
      phosphatase (pSEAP). At nitrogen to phosphate ratio (N/P) of 6.7, the polyplexes
      produced by coaxial EHDS had delivery efficiencies up to 2.6 times higher than
      those produced by bulk mixing. The N/P ratio and the structure of the EHDS used
      to make the polyplexes were crucial factors in determining the delivery
      efficiency.

PMID- 19845021
TI  - Discovering new cell populations.

PMID- 19845025
TI  - Technical note: Efficiency of total demineralization and ion-exchange column for
      DNA extraction from bone.
AB  - We investigated whether a combination of recently introduced methods, total
      demineralization and ion-exchange columns, would increase DNA recovery from old
      bone. Ten bone samples taken after a burial period of approximately 60 years were
      used in this study. Bone powder was digested using total or incomplete
      demineralization. DNA was extracted by the standard organic method. The DNA
      extract was purified with ion-exchange columns or QIAquick spin columns. The
      efficiency of different DNA extraction methods was compared in terms of DNA
      concentration, inhibitors generated by real-time PCR, and conventional STR typing
      results. The mean DNA concentration using the total demineralization method is
      approximately 3 times higher than that using the incomplete demineralization
      method. For DNA purification, the method using QIAquick spin columns appeared to
      yield approximately double the DNA than the method using ion-exchange columns.
      Furthermore, 2 out of 10 samples showed higher levels of inhibition with C(T)
      values of IPC > or =30 cycles when using only ion-exchange columns. In STR
      results, total demineralization yielded more locus profiles by 4.2 loci than
      incomplete demineralization, and QIAquick spin columns also yielded more locus
      profiles by 3.5 loci than ion-exchange columns. Total demineralization of bone
      powder significantly increased DNA yield and improved STR typing results.
      However, the use of ion-exchange columns was not efficient when compared with the
      method using QIAquick spin columns. It is suggested that the combination of total
      demineralization and QIAquick spin columns lead to greatly improved STR typing
      results.

PMID- 19845026
TI  - Plasma phenylalanine level in dopa-responsive dystonia.

PMID- 19845027
TI  - Estimation of adult skeletal age-at-death using the Sugeno fuzzy integral.
AB  - Age-at-death estimation of an individual skeleton is important to forensic and
      biological anthropologists for identification and demographic analysis, but it
      has been shown that the current aging methods are often unreliable because of
      skeletal variation and taphonomic factors. Multifactorial methods have been shown
      to produce better results when determining age-at-death than single indicator
      methods. However, multifactorial methods are difficult to apply to single or
      poorly preserved skeletons, and they rarely provide the investigator with
      information about the reliability of the estimate. The goal of this research is
      to examine the validity of the Sugeno fuzzy integral as a multifactorial method
      for modeling age-at-death of an individual skeleton. This approach is novel
      because it produces an informed decision of age-at-death utilizing multiple age
      indicators while also taking into consideration the accuracies of the methods and
      the condition of the bone being examined. Additionally, the Sugeno fuzzy integral
      does not require the use of a population and it qualitatively produces easily
      interpreted graphical results. Examples are presented applying three commonly
      used aging methods on a known-age skeletal sample from the Terry Anatomical
      Collection. This method produces results that are more accurate and with smaller
      intervals than single indicator methods.

PMID- 19845028
TI  - A survey of entodiniomorphid ciliates in chimpanzees and bonobos.
AB  - Intestinal entodiniomorphid ciliates are commonly diagnosed in the feces of wild
      apes of the genera Pan and Gorilla. Although some authors previously considered
      entodiniomorphid ciliates as possible pathogens, a symbiotic function within the
      intestinal ecosystem and their participation in fiber fermentation has been
      proposed. Previous studies have suggested that these ciliates gradually disappear
      under captive conditions. We studied entodiniomorphid ciliates in 23 captive
      groups of chimpanzees, three groups of captive bonobos and six populations of
      wild chimpanzees. Fecal samples were examined using Sheather's flotation and
      Merthiolate-Iodine-Formaldehyde Concentration (MIFC) methods. We quantified the
      number of ciliates per gram of feces. The MIFC method was more sensitive for
      ciliate detection than the flotation method. Ciliates of genus Troglodytella were
      detected in 13 groups of captive chimpanzees, two groups of bonobos and in all
      wild chimpanzee populations studied. The absence of entodiniomorphids in some
      captive groups might be because of the extensive administration of
      chemotherapeutics in the past or a side-effect of the causative or prophylactic
      administration of antiparasitic or antibiotic drugs. The infection intensities of
      ciliates in captive chimpanzees were higher than in wild ones. We suppose that
      the over-supply of starch, typical in captive primate diets, might induce an
      increase in the number of ciliates. In vitro studies on metabolism and
      biochemical activities of entodiniomorphids are needed to clarify their role in
      ape digestion.

PMID- 19845029
TI  - Cytopathologist-performed ultrasound-guided fine-needle aspiration of parathyroid
      lesions.
AB  - The gold standard to determine the cause of primary hyperparathyroidism (PHPT) is
      bilateral neck exploration. As most cases are caused by parathyroid adenoma,
      there is a movement toward preoperative localization of the abnormal gland by
      ultrasound and/or Tc(99)-sestamibi scan and minimally invasive parathyroidectomy.
      Nonpalpable thyroid nodules are common and cannot be differentiated from
      parathyroid lesions by imaging alone. This study examines cytopathologist
      performed ultrasound-guided fine-needle aspiration (UG-FNA) in diagnosis of
      parathyroid lesions. Between January 1, 2007 and December 31, 2008, seven
      patients with PHPT or other parathyroid lesions with one or more sonographically
      visible thyroid masses underwent cytopathologist-performed UG-FNA with immediate
      cytological evaluation (ICE). One mass was palpable and nine were nonpalpable.
      Three parathyroid adenomas, two benign colloid nodules, one papillary carcinoma,
      three parathyroid cysts, and one thyroid cyst were diagnosed. The nodules in
      three patients with parathyroid adenomas were identified as follicular
      lesion/neoplasm on ICE. Additional UG-FNA passes were made to obtain tissue for
      immunohistochemistry stains, which confirmed parathyroid origin. Two of these
      patients had a separate benign colloid nodule and one had a thyroid cyst
      diagnosed by UG-FNA. The PHPT patient with papillary carcinoma on UG-FNA had the
      malignancy confirmed at surgery and a sonographically occult parathyroid adenoma.
      The three patients with thyroid cysts identified by radiology were suspected of
      being parathyroid cysts on the basis of real-time sonographic features at the
      biopsy table. The clear cyst fluid obtained by UG-FNA had markedly elevated PTH.
      Cytopathologist-performed UG-FNA can distinguish between parathyroid and thyroid
      nodules in patients with suspected parathyroid lesions.

PMID- 19845030
TI  - Anal pap smear for high risk women.

PMID- 19845031
TI  - Cytoplasmic vacuoles can occur as an artifact in small cell carcinoma smears.

PMID- 19845032
TI  - Histiocytic sarcoma with interdigitating dendritic cell differentiation: a case
      report with fine needle aspiration cytology and review of literature.
AB  - A hybrid histiocytic sarcoma-interdigitating dendritic cell sarcoma was found in
      a small perinephric lymph node of an asymptomatic 80-year-old man, who presented
      a year ago with two small foci of lung metastasis found during routine chest X
      ray. Fine needle aspiration cytology demonstrated interconnecting long and thin
      cell processes radiating from dendrite-like neoplastic cells with oval,
      enlongated, reniform, and irregular nuclei with vesicular chromatin and distinct
      nucleoli. Histology showed spindled epitheliod and histiocytic cells with
      abundant, slightly eosinophilic cytoplasm with indistinct cell borders and
      forming fascicles in a vague storiform pattern with interspersed T-lymphocytes.
      Immunohistochemically, the neoplastic cells were strongly positive for
      histiocytic markers: CD163, CD68, lysozyme, and PU.1, as well as strongly
      positive for dendritic cell markers: S100 and fascin, but were negative for CD1a
      (Langerhans cell marker), CD21/CD35 (follicular dendritic cell markers), B-cell,
      and T cell markers. This case is compared to the four hybrid histiocytic
      dendritic sarcomas reported since 1983.

PMID- 19845033
TI  - Nephroblastoma is a success of paediatric oncologic therapy. How further can we
      go?: Results of a cyto-histologic correlation study.
AB  - Nephroblastoma is a success of paediatric oncologic therapy, yet, there are still
      some cases where favourable response to preoperative chemotherapy is not
      achieved. Fine needle biopsy has the role of diagnostic confirmation and,
      idyllically of predicting a response to preoperative chemotherapy. To advance in
      this aim, we retrieved a total of 14 nephroblastomas, (seven male patients and
      seven female with a mean age of 44.4 months), diagnosed in our department by fine
      needle biopsy and submitted afterward to chemotherapy and nephrectomy, in the
      last 10 years. Correlation between cytologic features, (morphology, cell death,
      and proliferation (Ki-67 labelling index), and post chemotherapy tumour
      evaluation was done. Cytologic pattern per se was not predictive of histologic
      tumour classification (P = 0.6061). We did not find any correlation between the
      percentage of necrosis and apoptosis (P = 0.682) in cytologic smears and
      histologic regressive changes but when both these two criteria coexisted in
      cytologic blastemal component of nephroblastomas, this fact seemed to lead to a
      favourable response of the tumour to chemotherapy. When evaluation of Ki-67
      labelling index was done in the blastematous component present in the smears,
      divergent results were obtained. The small number of cases prevented any firm
      conclusions. By summing up, our results support the idea that there are probably
      two types of blastema in nephroblastoma with different "suicide" potential and
      chemotherapeutic response. Further studies should be performed to stratify the
      influence of necrosis, apoptosis, and proliferation in chemosensivity of
      nephroblastomas.

PMID- 19845034
TI  - Pulmonary crystal-storing histiocytosis diagnosed by computed tomography-guided
      fine-needle aspiration.
AB  - Crystal-storing histiocytosis (CSH) is a rare process most often occurring in
      conjunction with an underlying hematopoietic neoplasm, usually multiple myeloma
      or low-grade B-cell lymphoma. We report the first case of pulmonary CSH diagnosed
      by fine-needle aspiration biopsy. A patient with a history of urothelial
      carcinoma developed a lung nodule, which was evaluated by fine-needle aspiration
      biopsy. Cytologic examination revealed macrophages with abundant cytoplasmic
      crystals diagnostic of CSH. Based on this cytologic interpretation, additional
      clinical laboratory evaluation was pursued and revealed a previously unknown
      monoclonal serum protein. CSH must be differentiated from other non-neoplastic
      and neoplastic lesions and when diagnosed, should trigger a search for an
      underlying lymphoproliferative disorder.

PMID- 19845035
TI  - A pilot study using nabilone for symptomatic treatment in Huntington's disease.
AB  - Pilot study of nabilone in Huntington's disease (HD). Double-blind, placebo
      controlled, cross-over study of nabilone versus placebo. Primary outcome, Unified
      Huntington's Disease Rating Scale (UHDRS) total motor score. Secondary measures:
      UHDRS subsections for chorea, cognition and behavior, and neuropsychiatric
      inventory (NPI). 44 randomized patients received either nabilone (1 or 2 mg)
      followed by placebo (n = 22), or placebo followed by nabilone (n = 22).
      Recruiting was straightforward. Nabilone safe and well tolerated, no psychotic
      episodes. Assessment of either dose of nabilone versus placebo showed a treatment
      difference of 0.86 (95% CI: -1.8 to 3.52) for total motor score; 1.68 (95% CI:
      0.44 to 2.92) for chorea; 3.57 (95% CI: -3.41 to 10.55) for UHDRS cognition; 4.01
      (95% CI: -0.11 to 8.13) for UHDRS behavior, and 6.43 (95% CI: 0.2 to 12.66) for
      the NPI. Larger longer RCT of nabilone in HD is feasible and warranted.

PMID- 19845036
TI  - Transient expression of human TorsinA enhances secretion of two functionally
      distinct proteins in cultured Chinese hamster ovary (CHO) cells.
AB  - Cultured mammalian cells, particularly Chinese hamster ovary (CHO) cells, are
      widely exploited as hosts for the production of recombinant proteins, but often
      yields are limiting. Such limitations may be due in part to the misfolding and
      subsequent degradation of the heterologous proteins. Consequently we have
      determined whether transiently co-expressing yeast and/or mammalian chaperones
      that act to disaggregate proteins, in CHO cell lines, improve the levels of
      either a cytoplasmic (Fluc) or secreted (Gluc) form of luciferase or an
      immunoglobulin IgG4 molecule. Over-expression of the yeast 'protein disaggregase'
      Hsp104 in a CHO cell line increased the levels of Fluc more significantly than
      for Gluc although levels were not further elevated by over-expression of the
      yeast or mammalian Hsp70/40 chaperones. Over-expression of TorsinA, a mammalian
      protein related in sequence to yeast Hsp104, but located in the ER, significantly
      increased the level of secreted Gluc from CHO cells by 2.5-fold and to a lesser
      extent the secreted levels of a recombinant IgG4 molecule. These observations
      indicate that the over-expression of yeast Hsp104 in mammalian cells can improve
      recombinant protein yield and that over-expression of TorsinA in the ER can
      promote secretion of heterologous proteins from mammalian cells.

PMID- 19845037
TI  - Treatment of insulin resistance with metformin in naive genotype 1 chronic
      hepatitis C patients receiving peginterferon alfa-2a plus ribavirin.
AB  - Insulin resistance affects sustained virological response (SVR) in chronic
      hepatitis C. To know whether adding metformin to standard antiviral treatment
      improves SVR, we conducted a prospective, multicentered, randomized, double
      blinded, placebo-controlled trial in 19 Spanish hospitals, including 123
      consecutive patients with genotype 1 chronic hepatitis C and insulin resistance.
      Patients were randomized to receive either metformin (arm A; n = 59) or placebo
      (arm B; n = 64) in addition to peginterferon alfa-2a (180 microg/week) and
      ribavirin (1000-1200 mg/day). The primary end point was SVR, and secondary
      endpoints were viral clearance at weeks 12, 24, and 48, and changes in the
      homeostasis model assessment (HOMA) index over the first 24 weeks. There were no
      differences between arms at baseline. In the intent-to-treat analysis, SVR was
      observed in 53% versus 42% in arm A and arm B, respectively (P = NS). In the
      subgroup analyses, SVR was higher in females (n = 54) receiving metformin: arm A,
      58% (15/26) versus 29% (8/28) arm B (P = 0.03). In the per protocol analysis
      (PPA; n = 101), SVR was 67% in arm A and 49% in arm B (P = 0.06). Viral decline
      during the first 12 weeks was greater in females receiving metformin: -4.88
      (1.18) versus -4.0 (1.44) (P = 0.021), whereas no differences were seen in males.
      The triple therapy was well tolerated, but diarrhea was more often seen in arm A
      (34% versus 11%; P < 0.05). CONCLUSION: Adding metformin to peginterferon and
      ribavirin was safe and improved insulin sensitivity. Although the study failed to
      show a statistically significant difference between arms, it did show an improved
      SVR in females.

PMID- 19845038
TI  - Determination of polyphenolics in extracts of Potentilla species by high
      performance thin-layer chromatography photodensitometry method.
AB  - INTRODUCTION: Separation of polyphenolics in different plant materials using high
      performance thin-layer chromatography (HPTLC) represents an effective method for
      their detection and quantification. OBJECTIVE: To develop a simple, specific,
      precise, sensitive and accurate method for the simultaneous quantification of
      tiliroside (TRS), methyl brevifolincarboxylate (MBR) and ellagic acid (EA) in a
      plant extract using the HPTLC-photodensitometry method. METHODOLOGY: Aerial parts
      of the selected Potentilla species, P. anserina, P. erecta, P. grandiflora and P.
      nepalensis var. 'Miss Willmott', were extracted with methanol. After solvent
      evaporation, the methanolic extracts were diluted with water and successively
      partitioned between chloroform and then diethyl ether. The diethyl ether extracts
      from each sample were used for quantification. The analyses were performed on
      HPTLC precoated silica gel 60F(254) plates with toluene-ethyl formate-formic acid
      (6 : 4 : 1 v/v/v) as the mobile phase (distance of 7.5 cm). Densitometric
      detections of TRS, MBR and EA were performed at 320, 287 and 280 nm,
      respectively. The amounts of these compounds were calculated using the regression
      equations of the calibration curves, which were linear within a range of 0.05-0.5
      microg/spot (R(2) = 0.9957) for TRS, 0.05-0.525 microg/spot (R(2) = 0.9965) for
      MBR and 0.0525-0.5 microg/spot (R(2) = 0.9998) for EA. RESULTS: The amounts of
      marker compounds measured by the method developed are expressed in mg/g of dry
      extracts. TRS ranged from 20.3 +/- 0.3 mg/g for P. erecta herbs to 197.7 +/- 2.9
      mg/g for P. grandiflora herbs; MBR ranged from 5.0 +/- 0.6 mg/g for P. erecta
      herbs to 68.5 +/- 3.4 mg/g for P. nepalensis flowers; and EA ranged from 24.0 +/-
      0.6 mg/g for P. erecta herbs to 216.2 +/- 3.2 mg/g for P. anserina leaves.
      CONCLUSION: The proposed method was found to be relatively simple, specific,
      precise, sensitive and accurate and may be used for the routine assay of
      simultaneous determination of TRS, MBR and EA in other extracts and
      phytomedicines containing Potentilla species.

PMID- 19845039
TI  - Optimised separation procedures for the simultaneous assay of three plant
      hormones in liquid biofertilisers.
AB  - INTRODUCTION: The overuse of petrochemical-based synthetic fertilisers has caused
      detrimental effects to soil, water supplies, foods and animal health. This, in
      addition to increased awareness of organic farming, has generated considerable
      interest in the evaluation of renewable biofertilisers. OBJECTIVE: The three
      objectives of the current research were: (1) to evaluate and optimise a solid
      phase extraction procedure for extraction of three plant hormones, IAA, GA(3) and
      ABA from two model biofertilisers produced from coconut shells and pineapple
      peels; (2) to develop an HPLC analysis procedure for the simultaneous separation
      and quantification of three plant hormones (IAA, GA(3) and ABA); and (3) to
      evaluate the changes in three plant hormones levels at four different
      fermentation time periods and varying number of general bacteria, lactic acid
      bacteria and yeast. RESULT: An optimised procedure for sample preparation,
      separation and simultaneous analysis of three plant hormones [indole-3-acetic
      acid (IAA), gibberellic acid (GA(3)) and abscisic acid (ABA)] produced in liquid
      biofertilisers was developed. This method involves sample cleanup using a Sep
      pack OasisMAX cartridge containing mixed-mode anion-exchange and reverse-phase
      sorbents that provided optimum recovery of 85.6, 91.9 and 94.3%, respectively,
      for the three hormones, IAA, GA(3), and ABA. Baseline separation of three
      hormones was achieved using mobile phase consisting of 1% acetic acid and
      acetonitrile (75:25, v/v) at pH 4.0. The amounts of hormones produced in liquid
      biofertilisers were influenced by fruit types, fermentation time and total number
      of general bacteria, lactic acid bacteria and yeasts. The quantities of three
      plant hormones produced during fermentation correlated well with the total number
      of microorganisms present in the liquid biofertilisers. CONCLUSION: A simple and
      rapid sample preparation procedure followed by RP-HPLC with UV detection was
      optimised and developed for simultaneous quantification and identification of
      three plant hormones namely, IAA, GA(3) and ABA in the liquid biofertilisers.
      This procedure allows quantification of the three plant hormones in their natural
      states without any prior derivatisation step. The results presented illustrate
      that the contents of the three plant hormones depended on the type of fruit
      wastes, fermentation time and the number of microorganisms found in liquid
      biofertilisers. This method can be extended to determine the quantity of three
      hormones in other matrices. This assay procedure will aid in the development of
      liquid biofertilisers, a valuable alternative fertilisers to promote plant
      growth. This process will help farmers to reduce production cost and pollution
      problems.

PMID- 19845040
TI  - Candida albicans: fundamental research on an opportunistic human pathogen.

PMID- 19845041
TI  - Quorum sensing and fungal-bacterial interactions in Candida albicans: a
      communicative network regulating microbial coexistence and virulence.
AB  - Microorganisms have evolved a complex signature of communication termed quorum
      sensing (QS), which is based on the exchange and sensing of low molecular- weight
      signal compounds. The ability to communicate within the microbial population
      gives the advantage to coordinate a groups behaviour leading to a higher fitness
      in the environment. The polymorphic fungus Candida albicans is an opportunistic
      human pathogen able to regulate virulence traits through the production of at
      least two QS signal molecules: farnesol and tyrosol. The ability to adopt
      multiple morphotypes and form biofilms on infected surfaces are the most
      important pathogenic characteristics regulated by QS and are of clinical
      relevance. In fact, traditional antimicrobial approaches are often ineffective
      towards these characteristics. Moreover, the intimate association between C.
      albicans and other pathogens, such as Pseudomonas aeruginosa, increases the
      complexity of the infection system. This review outlines the current knowledge on
      fungal QS and fungal-bacterial interactions emphasizing on C. albicans. Further
      investigations need to concentrate on the molecular mechanisms and the genetic
      regulation of these phenomena in order to identify putative novel therapeutic
      options.

PMID- 19845043
TI  - Remembering Bernett L. Johnson, Jr, MD.

PMID- 19845044
TI  - Primary lesions were   more 18F-FDG avid in patients with distant spread than in 
      those without extensive disease.

PMID- 19845042
TI  - Massive induction of innate immune response to Candida albicans in the kidney in
      a murine intravenous challenge model.
AB  - In the experimental Candida albicans intravenous challenge model, the kidney is
      one of the main organs involved in disease. In progressive infection, fungal
      burdens are found to increase over time, with rapid increases occurring from 24 h
      postinfection. Renal transcriptional responses were analyzed at this time in the
      kidneys of mice infected by either a virulent or an attenuated C. albicans
      strain, allowing comparison of host responses in progressive and nonprogressive
      infection. The results of this study demonstrate that both infections share a
      common transcriptional response, consisting of functions associated with the
      acute-phase reaction. In addition, challenge with the virulent strain led to a
      massively increased expression of cytokine genes, other innate response genes and
      genes suggestive of initiation of the adaptive immune response. This immune
      response to C. albicans infection, which occurs only in progressive infection,
      may contribute to development of sepsis and, ultimately, host death.

PMID- 19845045
TI  - [La voluntad pedagogica de Cajal, presidente de la Jae].
AB  - This article has two aims. On one hand, it tries to point out the role of the
      Santiago Ramon y Cajal in the establishment and development of the "Junta para
      Ampiacion de Estudios e Investigaciones Cientificas" (JAE). On the other hand, it
      links the leadership of Cajal in this Institution to his teaching authority of
      young scientifics. This pedagogical will was showed with various facts along his
      intellectual path. It is appropriate to underline among them his effort in
      spreading science, his enthusiasm and engagement in order to change the
      educational structures of Spanish Society and his 25 year long Presidency of JAE,
      from 1907 until 1932.

PMID- 19845046
TI  - [El Laboratorio Foster de la Residencia de Senoritas. Las relaciones de la JAE
      con el International Institute for Girls in Spain, y la formacion de las jovenes
      cientificas espanolas].
AB  - In the first third of the twentieth century, relations among American and Spanish
      university women began; particularly the relationship between the JAE and the
      International Institute for Girls in Spain had a positive influence in the
      education of women scientists in Spain. An interchange of students and teachers
      came out from this relationship, and Spanish women received scholarships to stay
      in American universities. The history of the Foster Laboratory and some
      biographical notes of her founder are included in the paper.

PMID- 19845047
TI  - [Los laboratorios de la Junta para Ampliacion de Estudios e Investigaciones
      Cientificas (J.A.E.) y la Residencia de Estudiantes (1912-1939)].
AB  - The policy of promoting fellowships abroad by the JAE for young scientist had an
      important complement in the foundation of a series of small scientific
      laboratories and research centres joined basically under the National Institute
      of Science and the Residencia de Estudiantes. The present article offers a
      general perspective of the activities developed by some of those laboratories,
      their main protagonists and research groups, particularly those related to
      biomedical research. The scientific task developed by the Instituto Cajal and the
      Natural Sciences Museum is not directly considered, since other contributions in
      this monographic issue regard those institutions. The process of creation of
      small teaching and research laboratories since 1912 is shown, and their
      participation in the university experimental teaching during the 1920s,
      especially regarding the Residencia de Estudiantes laboratories. Among them, the
      Laboratory of General Physiology lead by Juan Negrin. The significance of his
      physiological school is shown as well as the starting point of the scientific
      career of Severo Ochoa.

PMID- 19845048
TI  - [Neurocience in the Junta para Ampliacion de Estudios].
AB  - The development of the Neurociencias in the Spain at the first third of the 20th
      century had a strong histological and pathological component. The work of
      Santiago Ramon and Cajal and Luis Simarro was continued by some excellent
      disciples: Nicolas Achucarro, Gonzalo Rodriguez Lafora, Fernando de Castro, etc.
      Some of them had to make compatible diverse occupations, even the professional
      exercise of psychiatry, before obtaining a modest - but stable - position of
      investigation. In spite of some misalignments in the institutional development of
      the centers and the personal biographical ups and downs, the Junta para
      Ampliacion de Estudios was the great institution that fomented the international
      formation of the investigators and equipped to them with the means to develop its
      work.

PMID- 19845049
TI  - His and hers heart disease.  Mounting evidence makes a case for a gender-based
      approach to heart disease.

PMID- 19845050
TI  - Counting every step you take.  Walking is the simplest form of exercise, and
      using a pedometer is a good way to get yourself to do it.

PMID- 19845051
TI  - Whiplash.  The harm may occur just before the neck jerks back and forward.

PMID- 19845053
TI  - Taking aim at the deadliest cancer.

PMID- 19845052
TI  - By the way, doctor.  I've heard that you can treat diabetes by taking an extract
      from cinnamon.  I suspect this is snake oil, but is there anything to it?

PMID- 19845054
TI  - Protecting vision from diabetic retinopathy.

PMID- 19845055
TI  - Women and stroke: the gender gap.

PMID- 19845056
TI  - Eight steps to put sleep trouble to rest.

PMID- 19845057
TI  - Is there any benefit from taking a multivitamin?

PMID- 19845058
TI  - I prefer ibuprofen over acetaminophen for arthritis pain relief.  But now my
      doctor suggests I take a narcotic pain reliever.  Is this safe?

PMID- 19845059
TI  - Re: Facemask-circumaxillary sutural distraction in early treatment of Class III
      malocclusion.

PMID- 19845060
TI  - Of Atkins and men: deviations from clinical definitions of mental retardation in
      death penalty cases.
AB  - Under Atkins v. Virginia, the Eighth Amendment exempts from execution individuals
      who meet the clinical definitions of mental retardation set forth by the American
      Association on Intellectual and Developmental Disabilities and the American
      Psychiatric Association. Both define mental retardation as significantly
      subaverage intellectual functioning accompanied by significant limitations in
      adaptive functioning, originating before the age of 18. Since Atkins, most
      jurisdictions have adopted definitions of mental retardation that conform to
      those definitions. But some states, looking often to stereotypes of persons with
      mental retardation, apply exclusion criteria that deviate from and are more
      restrictive than the accepted scientific and clinical definitions. These state
      deviations have the effect of excluding from Atkins's reach some individuals who
      plainly fall within the class it protects. This article focuses on the cases of
      Roger Cherry, Jeffrey Williams, Michael Stallings, and others, who represent an
      ever-growing number of individuals inappropriately excluded from Atkins. Left
      unaddressed, the state deviations discussed herein permit what Atkins does not:
      the death-sentencing and execution of some capital defendants who have mental
      retardation.

PMID- 19845061
TI  - Short communication: ATP-dependent deoxyribonuclease activity in segregated cell
      types of Caulobacter crescentus.
AB  - Partially purified bacterial extracts were prepared from segregated stalked and
      swarmer bacteria of Caulobacter crescentus and assayed for ATP-dependent
      deoxyribonuclease activity. This activity was found to be very low in the swarmer
      bacteria compared with a pure population of stalked cells or an asynchronous
      population of C. crescentus.

PMID- 19845062
TI  - Illustrations of the anatomical wax model collection in the "La Specola" Zoology
      Museum, Florence.
AB  - Anatomical illustration has evolved through the centuries, first having artistic
      and educational purposes and later more strictly medical objectives. Between the
      eleventh and fifteenth centuries, the analytical model (representation of
      individual parts, organs and systems) gave way to the composite model
      (description of the human body as a whole). Between the seventeenth and
      eighteenth centuries, there was a reversal of tendency: initially the anatomist
      requested the help of artists, but later the artist asked anatomists to check the
      accuracy of his work. In this way, anatomical illustration reached a high level
      of precision. This period also saw the creation of the "La Specola" Zoology
      Museum's collection of anatomical wax models. Initiated in the eighteenth
      century, it also included a series of contemporary colour illustrations executed
      by various artists. Most of the illustrations concern human anatomy, while a
      small number deal with comparative anatomy. These illustrations, each accompanied
      by one or more explanatory sheets, were produced to help explain the
      corresponding wax models. The anatomical wax model collection has been well
      preserved through the centuries, maintaining its ancient splendour, and it is the
      object of continuing research and restoration interventions.

PMID- 19845063
TI  - The botanical activities of George Edward Post (1838-1909).
AB  - George Edward Post wrote the first flora of the Middle East in English. His other
      botanical activities are less familiar. In addition to the flora, this paper
      discusses his teaching, fieldwork, contribution to Bible dictionaries, relations
      with the Boissier Herbarium in Geneva, establishment of the herbarium, and
      letters. Those letters are used here for the first time. Post corresponded with
      botanical luminaries of his day including Autran, Baker, Balfour, Barbey,
      Boissier, Bornmuller, Carruthers, Denslow, Haussknecht, Hooker, Schweinfurth,
      Thistleton-Dyer, Torrey, and Winkler. His long-term relationship with the
      herbarium at Geneva is highlighted. In addition, some of the lesser understood
      aspects of his life including chaplaincy during the American Civil War, and
      missionary to Syria are discussed.

PMID- 19845064
TI  - Sahagun's "Florentine codex," a little known Aztecan natural history of the
      Valley of Mexico.
AB  - Franciscan missionary Fray Bernardino de Sahagun arrived in New Spain (Mexico) in
      1529 to proselytize Aztecs surviving the Conquest, begun by Hernan Cortes in
      1519. About 1558 he commenced his huge opus "Historia general de las cosas de
      Nueva Espana" completed in Latin-Nahuatl manuscript in 1569. The best surviving
      version, the "Florentine Codex," 1579 in Spanish-Nahuatl, is the basis for the
      editions published since 1829. The first English translation was issued in 13
      volumes between 1950 and 1982, and the first facsimile was published in 1979.
      Book 11, "Earthly things," is a comprehensive natural history of the Valley of
      Mexico based on pre-Cortesian Aztec knowledge. Sahagun's work, largely unknown
      among English-speaking biologists, is an untapped treasury of information about
      Aztecan natural history. It also establishes the Aztecs as the preeminent
      pioneering naturalists of North American, and Sahagun and his colleagues as their
      documentarians.

PMID- 19845065
TI  - Translational medicine: Application of research to clinical practice.

PMID- 19845066
TI  - Preconception health: The missing link in the MNCH continuum of care.

PMID- 19845067
TI  - Autism Speaks Global Autism Public Health Initiative: Bridging gaps in autism
      awareness, research, and services around the world.

PMID- 19845068
TI  - The March of Dimes Global Network for Maternal and Infant Health: Harnessing the
      power of experts in lower-income countries to improve the health of women,
      mothers, newborns and babies.

PMID- 19845069
TI  - New Centers for Disease Control and Prevention publication on good laboratory
      practices for molecular genetics testing.

PMID- 19845070
TI  - [The diffusion of the human evolution in Spain and the JAE (1907-1939)].
AB  - During the first decades of the 20th century important findings of hominids
      fossil remains were made, enlarging the knowledge on Human Evolution. This period
      runs parallel to the activity of the Junta para Ampliacion de Estudios e
      Investigaciones Cientificas (JAE), an institution that helped to spread the new
      paleontological facts in Spain by providing funds for further studies and
      research, by the foundation of the Comision de Investigaciones Paleontologicas y
      Prehistoricas (CIPP) and the promotion of publications on Human Paleontology.

PMID- 19845072
TI  - [La Junta para Ampliacion de Estudios and the development of Spanish psychology].
AB  - During the last decades of the XIXth century, there was an awakening of
      consciousness for the need of a Spanish cultural renovation, of which one of the
      aims was to create and develop a Spanish science, resembling the scientific
      models already established in more advanced countries. There was a desire of
      Europeanization. Since it was a global social objective, it was necessary to
      start from the educator's training. In this climate the Junta para Ampliacion de
      Estudios e Investigaciones Cientificas, appeared. The role that the Junta played
      in Spanish research and in the innovation in the Psychopedagogical field through
      the first third of the XXth century was extremely important. The Junta's policy
      of scholarship was one of its most substantial achievements, for it made possible
      that the country reached in a few decades (1907-1936) the European scientific and
      psychological level. The relations among Spanish teachers and the Institute J.J.
      Rousseau is to highlighted, as "Geneva School" was to influence deeply the
      further development of psychology in Spain.

PMID- 19845071
TI  - [Genetics and the Junta para Ampliacion de Estudios e Investigaciones
      Cientificas].
AB  - The aim of this paper is to show the essential paper developed by the Junta para
      Ampliacion de Estudios in the origin of the Spanish genetics, using for that the
      most relevant researchers of the time, and between them two women, Jimena
      Fernandez de la Vega and Kate Pariser.

PMID- 19845073
TI  - Calcium channel blockers: differences between subclasses.
AB  - Calcium channel blockers (CCBs) share a common mechanism of action. However, the
      manner in which they exert their pharmacological effects is different between
      subclasses. Dihydropyridine (DHP) CCBs tend to be more potent vasodilators than
      non-dihydropyridine (non-DHP) agents, whereas the latter have more marked
      negative inotropic effects. Both subclasses have a similar capacity to lower BP;
      however, non-DHPs appear to offer potential advantages in the management of
      patients with chronic kidney disease and diabetic nephropathy. Representatives of
      both classes are now available in fixed-dose combinations containing an ACE
      inhibitor, the benefits of which include effective 24-hour BP control, a reduced
      incidence of adverse effects, and improved adherence.

PMID- 19845074
TI  - Dual therapy in hypertensive patients with coronary artery disease: the role of
      calcium channel blockers and beta-blockers.
AB  - BACKGROUND: The majority of hypertensive patients require combination therapy to
      achieve BP goals. Guidelines recommend dual therapy in newly diagnosed patients
      with BP > 160/100mm Hg. Calcium channel blocker (CCB)/ACE inhibitor and beta
      blocker (beta-adrenoceptor antagonists)/diuretic combinations are among regimens
      considered effective for BP control. ACE inhibitors, beta-blockers, and CCBs are
      recommended for use in patients after myocardial infarction (MI). Statistical
      modeling from INVEST (INternational VErapamil-Trandolapril STudy), suggests an
      association between dual and triple therapy and decreased risk of primary outcome
      ([PO] first occurrence of death, nonfatal MI, or nonfatal stroke) in patients
      with hypertension and coronary artery disease (CAD). OBJECTIVE AND METHODS: This
      study explores the utility of dual antihypertensive therapy by reporting BP and
      cardiovascular outcomes for INVEST patients who predominantly received either a
      CCB/ACE inhibitor or a beta-blocker/ diuretic regimen. RESULTS: 1170 patients
      were selected for analysis. After 24 months of treatment, BP control (Joint
      National Committee on Prevention, Detection, Evaluation, and Treatment of High
      Blood Pressure VI criteria) was 82.1% and 82.6% in the verapamil sustained
      release (SR) + trandolapril (Ve + Tr) and atenolol + hydrochlorothiazide (At +
      HCTZ) groups, respectively (p = 0.86). In Ve + Tr compared to At + HCTZ patients,
      adjusted risk for PO (hazard ratio [HR] 0.63; 95% CI 0.37, 1.05; p = 0.07) and
      unadjusted risks for secondary outcomes including death (HR 0.70; 95% CI 0.40,
      1.25), total MI (HR 0.82; 95% CI 0.35, 1.90), total stroke (HR 0.81; 95% CI 0.25,
      2.65) and new diabetes (HR 0.88; 95% CI 0.55, 1.41) were not statistically
      different. CONCLUSION: This analysis shows that combination treatment with either
      Ve+ Tr or At +- HCTZ is effective in achieving BP control and produces similar
      outcomes in hypertensive patients with CAD.

PMID- 19845075
TI  - Automation in the transfusion service.
AB  - Several instruments are now available for full automation of serologic testing in
      the transfusion service. Selection of an instrument is based on the facility's
      needs for testing and its resources. Installation, validation, interfacing, and
      operations require new skill sets for most transfusion service personnel. The
      newer instruments are suitable for use in smaller transfusion services, where
      procedures may not have changed recently and installing new equipment is a
      rarity. It is difficult to compare turnaround times and the cost of operating the
      instrument because the number of specimens and specific tests per run and test
      optimization features of the instrument's software all can vary. Automated
      instruments have proved to be suitable for testing most, but not all, specimens
      submitted for testing. While automation reduces overall turnaround time, the
      quickest way to determine a patient's blood type remains the manual tube test.
      Autoverification of results and placing these instruments in an automation line
      in a core laboratory may lie in the future.

PMID- 19845076
TI  - Transfusion service disaster planning.
AB  - The Mayo Clinic, in Rochester, Minnesota, recently set forth a directive to
      develop a Mayo Emergency Incident Command System (MEICS) plan to respond to major
      disasters. The MEICS plan that was developed interfaces with national response
      plans to ensure effective communication and coordination between our institution
      and local, state, and federal agencies to establish a common language and
      communication structure. The MEICS plan addresses multiple aspects of dealing
      with resource needs during a crisis, including the need for blood and transfusion
      medicine services. The MEICS plan was developed to supplement our current local
      emergency preparedness procedures and provide a mechanism for responding to the
      escalating severity of an emergency to deal with situations of a magnitude that
      is outside the normal experience. A plan was developed to interface the existing
      Transfusion Medicine disaster plan standard operating procedures (SOP) with the
      institutional and Department of Laboratory Medicine (DLMP) MEICS plans. The first
      step in developing this interface was defining MEICS. Other major steps were
      defining the chain of command, developing a method for visually indicating who is
      "in charge," planning communication, defining the actions to be taken, assessing
      resource needs, developing flowcharts and updating SOPs, and developing a blood
      rationing team to deal with anticipated blood shortages. Several key features of
      the interface and updated disaster plan that were developed are calling trees for
      response personnel, plans for relocating leadership to alternative command
      centers, and action sheets to assist with resource assessment. The action sheets
      also provide documentation of key actions by response personnel.

PMID- 19845077
TI  - A moving experience: lessons learned from relocating a reference laboratory.

PMID- 19845078
TI  - Cryopreserving and deglycerolizing sickle cell trait red blood cell components
      using an automated cell-processing system.
AB  - RBC components with rare phenotypes are sometimes required for patients with
      sickle cell disease, and these rare components can often be found among donors
      with sickle cell trait. Cryopreserving RBC components from sickle cell trait
      donors requires a modified deglycerolization method to preserve the integrity of
      the RBCs. This study evaluated the feasibility of using an automated cell
      processing system to cryopreserve and deglycerolize sickle cell trait donor RBC
      components. CP2D/AS-3 RBC components were collected from three donors with sickle
      cell trait. Each component was processed with an automated cell-processing system
      (ACP 215, Haemonetics Corp., Braintree, MA) and cryopreserved within 6 days of
      collection. The components were stored at -65 degrees C or less for at least 2
      days and were deglycerolized using the automated cell-processing system's
      standard procedure. Before cryopreservation and after deglycerolization, several
      variables were measured. Deglycerolization resulted in recovery of 43.0, 76.5,
      and 67.5 percent of RBCs from the three sickle-cell-trait donor components
      compared with 80 percent or greater for all six control components. A small, dark
      red, jelly-like mass was noted in the bowl of the disposable set after
      deglycerolization of each of the three RBC sickle cell trait components. The
      osmolalities of all three sickle cell trait components were less than 400
      mOsm/kg, but only one of the three was acceptable for a 14-day outdate. Freezing
      and deglycerolization of sickle cell trait donor RBC components with the
      automated cell-processing system resulted in recovery of some RBCs, but a
      decrease in RBC recovery was problematic. Modifications of the procedure are
      needed for processing sickle cell trait donor RBC components.

PMID- 19845079
TI  - Overt immediate hemolytic transfusion reaction attributable to anti-Wr(a).
AB  - Wr(a) is a low-prevalence antigen. Anti-Wr(a) is a relatively common antibody
      present in approximately 1 in 100 healthy blood donors. Anti-Wr(a) is reported to
      cause different degrees of hemolysis in transfusion and in HDN, ranging from
      benign to severe. This report describes an acute overt hemolytic transfusion
      reaction in a patient whose serum contained anti-Wr(a) and who received a Wr(a+)
      RBC component.

PMID- 19845080
TI  - Group O red blood cells in massive transfusion--when to pull the switch?

PMID- 19845081
TI  - A precisely matched blood transfusion is like a carefully chosen fine wine.

PMID- 19845082
TI  - "Role of echocardiography in catheter intervention in congenital heart defects".
AB  - Echocardiography has evolved over last 3 decades from M-mode echocardiography,
      two-dimensional echocardiography, Dopplerimaging, three-dimensional
      echocardiography to intravascular /intracardiac echocardiography with its immense
      role in evaluation of a patient with congenital heart disease. The refinement in
      echocardiography imaging technique has made echocardiography as the main stay in
      diagnosis and decision making in patient with congenital heart defects (CHD). It
      is used fr defining anatomy, hemodyanamic assessment, guiding and immediate
      assessment of procedural results as well as detection of complication. In this
      review article, we are discussing the role of echocardiography
      (transthoracic/transesophageal) in catheter interventions in congenital heart
      defects.

PMID- 19845083
TI  - Coarctation of aorta--intervention from neonates to adult life.
AB  - Coarctation of aorta is typically a discrete narrowing of the thoracic aorta just
      distal to the left subclavian artery. Managmnet of Coarctation of aorta depends
      upon age, clinical presentation, type of coarctation, associated arch hypoplasia,
      and associated heart defects as ventricular septal defect. In this article we are
      discussing management of coarctation of aorta from neonatal period to adult.

PMID- 19845084
TI  - Catheter interventions in miscellaneous lesions in CHD: ruptured sinus of
      Valsalva, coronary arteriovenous fistulas, and pulmonary arteriovenous fistulas.
AB  - This article reviews the transcatheter interventions for ruptured sinus of
      Valsalva, coronary arteriovenous fistulas, and pulmonary arteriovenous fistulas.
      The current day indications, the required hardware, and divergent techniques are
      described at length. A detail account of published literature on transcatheter
      interventions of these lesions is given. We shall review in this article the
      catheter interventions for these rare miscellaneous lesions in congenital heart
      disease (CHD)-rupture of sinus of Valsalva, coronary arteriovenous (AV) fistulas,
      and pulmonary AV fistulas. The indication and recommendation for the
      transcatheter intervention, the necessary hardware and technique, and the review
      of published data in this regard will be dealt in details.

PMID- 19845085
TI  - Management of complications that arise during transcatheter closure of atrial
      septal defects and patent ductus arteriosus.

PMID- 19845086
TI  - Transcatheter closure of patent ductus arteriosus.

PMID- 19845087
TI  - Psychodynamics of eating disorder behavior in sexual abuse survivors.
AB  - The author reviews the psychodynamics of eating disorder behaviors in women with
      childhood sexual abuse histories, with a focus on anorexia, bingeing, purging,
      and overeating. The various defenses and behaviors interact with each other
      through numerous different feedback loops. The same behavior can have multiple
      defensive functions and the same defensive function can be served by different
      behaviors. None of the behaviors is specific to childhood sexual abuse, but the
      abuse history modifies the content, heightens the intensity of the feelings being
      defended against, and should be taken into account in the therapy. Several
      examples of therapeutic strategies are also provided.

PMID- 19845088
TI  - From submission to autonomy: approaching independent decision making. A single
      case study in a randomized, controlled study of long-term effects of dynamic
      psychotherapy.
AB  - In the First Experimental Study of Transference Interpretations (FEST), showing
      the best treatment effects from dynamic psychotherapy with transference
      interpretations, one subgroup was female patients who had difficult relationships
      with others (low quality of object relations). The aim of the present study was
      to explore further a highly successful therapy for this subgroup with a single
      case study in a randomized, controlled study of long-term effects of dynamic
      psychotherapy with a patient who was depressed and felt exploitable. Case
      formulation, transcription of sessions, and repeated applications of self-reports
      and observer-rated measures, both during and after therapy, are used. Detailed
      observer ratings of the therapist-patient interaction, using Structural Analysis
      of Social Behaviour (SASB) showed increasing patient autonomy and high positive
      complementarity throughout the therapy. The therapist's countertransference
      feelings were almost exclusively positive. These findings coincide well with the
      patient's sequential improvement: quick recovery from depression, increased
      insight, and followed by improved interpersonal functioning and less
      exploitability.

PMID- 19845089
TI  - Is a psychodynamic perspective relevant to the clinical management of obsessive
      compulsive disorder?
AB  - Obsessive-compulsive disorder (OCD) can be a severe and disabling condition with
      considerable variability in clinical presentation, course, and treatment
      response. Based upon demonstrated efficacy in clinical trials, selective
      serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) have
      become the treatments of choice for patients with OCD. By contrast, psychodynamic
      formulations and treatments are often considered irrelevant or contraindicated.
      In the present paper, the authors present five clinical cases of OCD where
      psychodynamic understanding and/or treatment was essential for optimizing
      outcome. The authors suggest that a careful psychosocial history and dynamic
      formulation can enrich understanding in patients with OCD and may sometimes point
      to alternative or supplementary treatments. Psychodynamic interventions may be
      considered for two subgroups of patients: those with late-onset OCD that
      coincides with interpersonal stressors, and those having borderline personality
      disorder, for whom specialized forms of treatment, such as dynamic deconstructive
      psychotherapy, may be indicated.

PMID- 19845090
TI  - "I can't let anything go:" A case study with psychological testing of a patient
      with pathologic hoarding.
AB  - Pathologic hoarding is a symptom generally recognized as related to obsessional
      dynamics (Gutheil, 1959). The hoarder cannot, without great anxiety, tolerate
      separation from or dispose of his possessions. Thus the hoarder accumulates vast
      amount of possessions, often in such amounts as to compromise freedom of movement
      in the residence. Popular in tabloid reportage, such news items portray persons
      found dead among floor-to-ceiling piles of old newspapers and similar detritus,
      while in actual clinical practice such dramatic cases are not common (Bryk, 2005;
      Duenwald, 2004). More importantly, such individuals are rarely available for
      psychological intervention or testing, both because of social isolation and
      injury or death caused by the hoarded materials. Additionally, a majority of the
      current literature regarding hoarding is linked with Obsessive Compulsive
      Disorder (OCD), though other major disorders have been noted. This report
      describes a particular individual with characteristic features of hoarding, which
      is explored through formal psychological testing.

PMID- 19845091
TI  - Trauma, exposure, and world reconstruction.
AB  - This article presents a reconceptualization of trauma in terms of the damage it
      inflicts on the patient's conception of his or her world. The article includes
      (1) an analysis of how this view renders the symptoms of posttraumatic stress
      disorder (PTSD) intelligible, (2) a demonstration of how it integrates research
      findings on who is most vulnerable to PTSD, (3) a critique of the currently
      dominant "reprocessing of maladaptive memory structures" accounts of how exposure
      therapy works, and (4) a reanalysis of how exposure therapies achieve their
      salutary results.

PMID- 19845092
TI  - More certification options could lead to more EHR adoption.

PMID- 19845093
TI  - Readers' perspectives. Readers' poll October 2009.

PMID- 19845094
TI  - Supporting clinical decisions in the physician's office.

PMID- 19845095
TI  - Getting help with coding.

PMID- 19845096
TI  - Avoiding 'alert fatigue'.

PMID- 19845097
TI  - Trial runners. A two-physician practice goes on a roll with its EHR, generating
      extra revenue from clinical trials.

PMID- 19845098
TI  - Study of interpolation method in diagnosis of carpal tunnel syndrome and
      comparison with midpalm antideromic sensory method.
AB  - Carpal tunnel syndrome (CTS) is the most common focal compression neuropathy.
      There are a significant number of different methods available to evaluate a
      patient for median nerve compromise at the carpal tunnel. One of them is
      interpolation method created by Dr E.B. Bodofski. In our study Sensitivity of
      interpolation method was 85.5%, Specificity was 85%, Positive predictive value
      was 94.6% and Negative predictive value was 65.4%. These results are lower than
      Dr Bodofski results. Also in our study sensitivity of midpalm antidromic sensory
      method was 95.1%, Specificity was 95%, Positive predictive value was 98.3% and
      Negative predictive value was 86.4%, these results are higher than results of
      interpolation method. These show interpolation method is a good method (with high
      sensitivity & specificity) for diagnosis of mild CTS, but it's sensitivity &
      specificity are lower than antideromic sensory stimulation method at wrist &
      midpalm.

PMID- 19845099
TI  - The classification and identification of human somatic and parasympathetic nerve
      fibres including urinary bladder afferents and efferents is preserved following
      spinal cord injury.
AB  - Single-fibre extracellular action potentials were recorded with 2 pairs of wire
      electrodes from lower human sacral nerve roots during surgery. The roots from
      which was recorded from were used for morphometry. Nerve fibre groups were
      identified by conduction velocity distribution histograms of single afferent and
      efferent fibres and partly by nerve fibre diameter distribution histograms. The
      values of group conduction velocity and group nerve fibre diameter measured in
      the paraplegics were very similar to those obtained from brain-dead humans and
      patients with no spinal cord injury. Thus the classification and identification
      of nerve fibre groups remained preserved following spinal cord injury. Upon
      retrograde bladder filling the urinary bladder stretch and tension receptor
      afferent activities were increased; on two occasions they even fired when the
      bladder was empty. Two reasons are brought forward for a too small storage volume
      of the urinary bladder in paraplegics: too high afferent activity of the bladder
      due to changed receptor field transduction mechanisms and too low compliance.
      SUMMARY: 1. Single nerve fibre action potentials (APs) of lower sacral nerve
      roots were recorded extracellularly with 2 pairs of wire electrodes during an
      operation for implanting an anterior root stimulator for bladder control in 9
      humans with a spinal cord injury and a dyssynergia of the urinary bladder. Roots
      that were not saved and that were used to record from were later used for
      morphometry. 2. Nerve fibre groups were identified by conduction velocity
      distribution histograms of single afferent and efferent fibres and partly by
      nerve fibre diameter distribution histograms, and correlation analysis was
      performed. Group conduction velocity values were obtained additionally from
      compound action potentials (CAPs) evoked by electrical stimulation of nerve roots
      and the urinary bladder. 3. The group conduction velocities and group nerve fibre
      diameters had the following pair-values at 35.5 degrees C: Spindle afferents: SP1
      (65 m/s / 13.1 microm), SP2 (51/12.1); touch afferents: T1 (47/11.1), T2
      (39/10.1), T3 (27/9.1), T4 (19/8.1); urinary bladder afferents: S1 (41 m/s / -),
      ST (35/-); alpha-motoneurons: alpha 13 (-/14.4), alpha 12 (65 m/s /13.1 microm),
      alpha 11 (60?/12.1)[FF], alpha 2 (51/10.3)[FR], alpha 3 (41/8.2)[S]; gamma
      motoneurons: gamma(beta) (27/7.1), gamma 1 (21/6.6), gamma 21 (16/5.8), gamma 22
      (14/5.1); preganglionic parasympathetic motoneurons: (10 m/s / 3.7 microm). 4.
      The values of group conduction velocity and group nerve fibre diameter measured
      in the paraplegics were very similar to those obtained earlier from brain-dead
      humans and patients with no spinal cord injury. Also, the axon number and the
      axon density of myelinated fibres of lower sacral nerve roots remain unchanged
      following spinal cord injury. Thus the classification and identification of nerve
      fibre groups remained preservedfollowing spinal cord injury. A direct comparison
      can thus be made of natural impulse patterns of afferent and efferent nerve
      fibres between paraplegics (pathologic) and brain-dead humans (supraspinal
      destroyed CNS, in many respects physiologic). 5. When changing the root
      temperature from 32 degrees C to 35.5 degrees C, the group conduction velocities
      changed in the following way in one case: SP2: 40 m/s (32 degrees C) to 50 m/s
      (35.5%), S1: 31.3 to 40, ST: 25 to 33.8, M: 12.5 to 13.8; alpha 2: 40 to 50,
      alpha 3: 33 to 40. The group conduction velocities showed different temperature
      dependence apart from SP2 fibres and alpha 2-motoneurons. 6. Upon retrograde
      bladder filling the urinary bladder stretch (S1) and tension receptor afferent
      (ST) activity levels were undulating and increased. As compared to activity
      levels detected in a brain-dead human, S1 (designates afferents, not cord
      segment) and ST afferents fired even when the bladder was empty, with an activity
      level similar to those observed in a brain-dead human with the bladder half
      filled. Two reasons are brought forward for an too small storage volume of the
      urinary bladder in paraplegics: too high afferent activity of the bladder due to
      changed receptor field signal transduction mechanisms and too low compliance. 7.
      With the newly developed 'coordination dynamics therapy', applied early after
      spinal cord injury, such complications of bladder functioning can be avoided; the
      bladder can causally be cured in severe spinal cord injury.

PMID- 19845100
TI  - EMLA cream for carpal tunnel syndrome: how it compares with steroid injection.
AB  - BACKGROUND: A standard treatment option for carpal tunnel syndrome (CTS) is local
      injection of anesthetic-corticosteroid. This clinical trial was designed to
      compare the safety and efficacy of daily application of the EMLA cream (lidocaine
      2.5% plus prilocaine 2.5%) with that of a single injection of methyl prednisolone
      acetate (Depo-Medrol) 40 mg. METHODS: In this randomized, parallel-group, open
      label, single-center, case-controlled, prospective study, 65 participants (70
      hands) aged 18-75 years with clinical & electrodiagnostic evidences of CTS were
      randomized to receive either the EMLA cream (n = 30 patients, 35 hands, group 1)
      or one injection of methylprednisolone acetate 40 mg at wrist (n = 35 patients,
      group 2). Outcome assessments included the visual analog scale and clinical
      assessment. RESULTS: After 4 weeks of treatment, patients in both groups reported
      significant changes (P < 0.001) in pain intensity. Both treatments were well
      tolerated, with treatment-related adverse events (AEs) reported in 2 patients in
      group 1 (5.7%) and 10 patients in group 2 (28.5%) No systemic treatment-related
      AEs were observed with the EMLA cream. CONCLUSION: EMLA cream was effective in
      reducing pain associated with CTS and well tolerated and it may offer patients
      with CTS an effective, noninvasive symptomatic treatment.

PMID- 19845101
TI  - Correlation between bite force and electromyographic activity in dentate and
      partially edentulous individuals.
AB  - Dental absence interferes in the physiological functioning of the masticatory
      system, promoting occlusal and functional alterations. The purpose of this study
      was to verify maximal bite force and maximal bite force correlated with
      electromyographic activity in 14 partially edentulous and 14 dentate individuals.
      Bite force in right and left molar and incisor regions were registered using a
      dynamometer with capacity of up to 1000N, adapted for oral conditions and at the
      same time electromyography was performed using Myosystem-Br1 with electrodes
      positioned on right and left masseter and temporalis muscles, and one reference
      electrode on the frontal bone. The highest value out of three recordings was
      considered the individual's maximal bite force. Statistical analysis of the bite
      force data was performed by means of t-test and Pearson's bivariate correlation
      test was used for the analysis between bite and electromyographic activity using
      SPSS 12.0 software. Dentate individuals showed greater maximal bite force in the
      three regions. Correlations between electromyographic activity and bite force in
      the dentate group obtained positive coefficients for every muscle in the right
      molar region, for the left temporalis in the left molar region, and for every
      muscle in the incisive region. For the partially edentulous group, only the left
      temporalis muscle presented a positive correlation in the right molar region,
      there was positive correlation for the right masseter and right and left
      temporalis in the left molar region, and, in the incisive region, every muscle
      presented negative correlation. These data evidence the strong influence of
      dental loss over the maximal bite force and small correlation between bite force
      and electromyographic activity.

PMID- 19845102
TI  - Abnormalities induced in reciprocal inhibition between orbicularis oculi and
      levator palpebrae following peripheral facial palsy.
AB  - Peripheral Facial palsy (PFP) is generally considered a benign condition with
      good recovery and no sequelae. Yet, a distortion in the gesture and abnormal
      blinking, as those typically found in blepharospasm, can potentially develop
      early on. Such abnormal movements seem to be related to remodelling mechanisms
      that take place in the process of recovery. We report 2 cases where such clinical
      features became evident following an idiopathic PFP, as a result of reciprocal
      inhibition of orbicularis oculi and levator palpebrae. Hence, the
      neurophysiological study revealed an increased frequency in the blinking, with
      bilateral trigeminal-facial facilitation and, most notably, a disturbance that
      only became evident when the eyes were maintained wide open. Interestingly, those
      features were not reproduced in other tasks where the blinking conditions had not
      been altered. Our findings suggest that sensory inputs (reflex afferent pathways)
      are involved in such abnormal movements. The insufficient eyelid closure
      (lagophthalmus) in the context of PFP is likely to account for the exaggerated
      corneal vulnerability, thus resulting in abnormal mechanisms of adaptation.

PMID- 19845103
TI  - Association between the electromyographic fatigue threshold and ventilatory
      threshold.
AB  - The objective of this study is to verify the coincidence between the occurrence
      of the electromyographic fatigue threshold (EMGth) and the ventilatory threshold
      (Vth) in an incremental test in the cyclosimulator, as well as to compare the
      calculation of the RMS from the EMG signal using different time windows. Thirteen
      male cyclists (73.7 +/- 12.4 kg and 174.3 +/- 6.2 cm) performed a ramp
      incremental test (TI) in a cyclosimulator until voluntary exhaustion. Before the
      start of each TI subjects had the active bipolar electrodes placed over the
      superficial muscles of the quadriceps femoris (QF) of the right leg: rectus
      femoris (RF), vastus medialis (VM) and vastus lateralis (VL). The paired
      student's t test, pearson's correlation coefficient and the analysis method
      described by Bland and Altman for the determination of the concordance level were
      used for statistical analysis. The significance level adopted was P < 0.05.
      Although no significant differences were found between Vth and the EMGth
      calculated from windows of 2, 5, 10, 30 and 60 seconds in the studied muscles, it
      is suggested that the EMGth values determined from the calculation of the RMS
      curve with windows of 5 and 10 seconds seem to be more appropriate for the
      calculation of the RMS curve and determination of EMGth from visual inspection.

PMID- 19845104
TI  - The efficiency of pedaling and the muscular recruitment are improved with
      increase of the cadence in cyclists and non-cyclists.
AB  - The objective of this study was to compare the efficiency of pedaling (EP) and
      the electromyographic activity (EMG) between cyclists and non-cyclists during
      cycling in different cadences. Using a cyclosimulator, 12 cyclists (26.5 +/- 4.5
      years; 68.2 +/- 10.5 kg; 175.6 +/- 8.2 cm) and 9 non-cyclists (25.1 +/- 4.3
      years; 72.6 +/- 9.8 kg; 174.6 +/- 6.2 cm), performed a maximum incremental test
      (ITmax), and subsequently, two constant load tests (Tconst) in different cadences
      (60 and 90 rpm) at the intensity of the electromyographic fatigue threshold
      (EMGth) determined in ITmax. Before the Tconst, the subjects performed a maximum
      isometric voluntary contraction (MIVC) for the normalization of the EMG data of
      Tconst. During Tconst, the EMG of the studied muscles was recorded, as well as
      the EP Although there was a trend of higher values in all occasions for the
      cyclists, there were no statistical differences in EP and the EMG when compared
      in a same cadence between groups. However, when the EMG is compared in different
      cadences in the same group, there was a significant increase (p < 0.05) in the
      muscles that work during the recovery phase with the increase in cadence, in both
      groups, being more evident in the cyclists. In conclusion, the hypothesis that
      cyclists had better technique than non-cyclists was not confirmed statistically.
      However, it was found that the increase in cadence improves the EP and the
      recruitment in both groups.

PMID- 19845105
TI  - Polyomavirus-associated nephropathy: critical issues in virological monitoring.
AB  - Polyomavirus-associated nephropathy is one of the most common viral complications
      in renal transplant recipients. Viral replication is the single common feature of
      all patients at risk of nephropathy. Therefore, screening for virus replication
      allows for the identification of patients at risk of developing nephropathy and
      permits earlier intervention, in particular a pre-emptive reduction of
      immunosuppression, with improvement of outcome. This paper describes the modes of
      virological monitoring and its role in the clinical management of renal
      transplant patients.

PMID- 19845106
TI  - Multicenter quality control study for human cytomegalovirus DNAemia
      quantification.
AB  - Standardized protocols and methods for virological monitoring are mandatory for
      the correct surveillance of human cytomegalovirus (HCMV) infection in
      transplanted patients receiving pre-emptive therapy. Fifteen Italian viral
      diagnostic laboratories belonging to different transplantation centers
      participated in the external Quality Control Programme for Molecular Diagnostics
      of HCMV-DNA by using two in-house and five commercial methods for HCMV-DNA
      quantification. The different methods shared 100% specificity, and sensitivity
      reached 100% when samples containing > 1,000 copies/ml were considered. The
      variability range was wide (about 2 log10) for samples containing a lower amount
      of HCMV-DNA (< 1,000 copies/ml), but it decreased with increasing concentrations
      of HCMV-DNA. For HCMV-DNA levels > or = 5,000 copies/ml, the different methods
      provided results within a +/- 0.5 log10 variability range, while the 80% range
      (range in which 80% of results obtained will fall) was within +/- 0.3 log10 or
      less. An acceptable level of variability was reached among different in-house and
      commercial methods for HCMV-DNA quantification in samples containing a clinically
      significant viral DNA amount. Based on these data, standardized cutoffs
      established for pre-emptive therapy in different transplantation centers should
      provide comparable clinical and virological results among centers.

PMID- 19845107
TI  - Beijing/W and major spoligotype families of Mycobacterium tuberculosis strains
      isolated from tuberculosis patients in Eastern Turkey.
AB  - The aim of this study was to determine the Beijing/W family and major
      phylogenetic clades of Mycobacterium tuberculosis strains of tuberculosis
      patients in a city with a tuberculosis incidence higher than the country average.
      A total of 220 M. tuberculosis strains isolated over a period of more than four
      years were typed by spoligotyping. Spoligotyping resulted in 64 different
      patterns, 38 (17.3%) of which were unique, and 26 were clusters including 182
      (82.7%) strains. The major shared types were ST 53 (n = 55, 25%), ST 41 (LAM7
      TUR; n = 19, 8.6%), and ST 284 (n = 15, 6.8%). The major clades observed ranked
      in the following order: ill-defined T superfamily (n = 112, 50.9%); Latino
      American-Mediterranean (LAM; n = 33, 15%); Haarlem (n = 24, 10.9%); and the S
      family (n = 9, 4.1%). Three strains were in the Beijing family. A high number of
      strains (33 strains) showed patterns that did not fall within any of the major
      clades described. M. tuberculosis strains in Malatya have both STs showing a
      widespread distribution over the world and those restricted to this city,
      confirming the highly diverse nature of tuberculosis. Our results suggest that
      the Beijing clade, which is more prevalent among the strains with MDR and
      isoniazid resistance, is currently not a problem in Eastern Turkey.

PMID- 19845108
TI  - Distribution of different carbapenem resistant clones of Acinetobacter baumannii
      in Tehran hospitals.
AB  - The MICs of imipenem, meropenem, piperacillin-tazobactam, cefotaxime, polymixin B
      and tigecycline against 80 isolates of Acintobacter baumanii from 6 hospitals
      were determined. A multiplex-PCR was used to detect the genes encoding
      carbapenemases. Field Inversion Gel Electrophoresis (FIGE) was then used to
      investigate the genetic relationships among the carbapenem-resistant isolates.
      Only 7 isolates were resistant to polymixin B and tigecycline (MIC = 16). All
      isolates were positive for at least 2 carbapenemase genes. At least 10 distinct
      clones were detected by FIGE. A dominant pattern designated as pulsotype A
      consisting of 23 isolates was detected from 4 hospitals. The majority of isolates
      in this pulsotype had a bla(OXA-51/23-like) and bla(OXA-51/24-like) carbapenemase
      genes and cultured from the patients at burns and ICU. The pan drug resistant
      isolates belonged to different FIGE patterns. Nosocomial infections with
      different clones of Acintobacter baumanii occur at Tehran hospitals. However,
      inter-hospital transmission with certain pulsotypes is likely.

PMID- 19845109
TI  - Pseudo-outbreak of Serratia marcescens in a tertiary care hospital.
AB  - The aim of this study was to describe a pseudo-outbreak due to Serratia
      marcescens associated with laboratory contamination, and also the epidemiologic
      and laboratory methods used to determine the source of contamination. An apparent
      increase in positive culture results for Serratia marcescens was observed in the
      Clinical Microbiology Laboratory of Kocaeli University Hospital between September
      and November 2007. An outbreak investigation including retrospective and
      prospective studies using chart review, environmental sampling and random
      arbitrary polymorphic DNA-polymerase chain reaction (RAPD-PCR) of randomly
      selected isolates were performed by the Infection Control Committee. Nine out of
      67 strains belonged to a real infection. S. marcescens was also isolated from
      saline solution in the specimen processing area of the laboratory. It was
      recognized that the technician has been using the same stock saline solution for
      processing specimens without changing the injector. RAPD patterns of the clinical
      isolates were identical to the pattern of saline strain. The contaminated saline
      solution was discarded, the technician was trained and no additional cases of
      suspected contamination have been observed. This pseudo-outbreak emphasize the
      importance of the observation of specimen processing procedures and the training
      of laboratory workers.

PMID- 19845110
TI  - Typing of Pseudomonas aeruginosa isolated from patients with VAP in an intensive
      care unit.
AB  - Aim of this study was to characterize isolates of Pseudomonas aeruginosa
      responsible for ventilator-associated pneumonia (VAP) in patients admitted to an
      ICU in order to evaluate a possible strain clonality. The study was performed
      from October 2004 to June 2005 in one Southern Italy ICU and 29 patients
      suspected of having VAP were enrolled. The etiology of VAP was established by
      quantitative cultures of endotracheal aspirations. Molecular characterization was
      carried out by PFGE. P. aeruginosa was responsible for 51% of all cases of VAP
      (15/29) and 12/15 strains were multi-drug resistant. High mortality (44.8%) was
      connected to this pathogen and evidence of strain clonality was found. The early
      identification of strain clonality and the application of infection control
      procedures are necessary to avoid the spread of pathogens such as P. aeruginosa
      involved in nosocomial infections.

PMID- 19845111
TI  - Determination of the expression of lymphocyte surface markers and cytokine levels
      in a mouse model of Plasmodium berghei.
AB  - This study aimed to determine the changes in lymphocyte surface markers and
      cytokine profiles during a malarial infection in a mouse model of malaria.
      Mononuclear cells obtained from the spleens of the mice infected with Plasmodium
      berghei (P. berghei) were stained with anti-mouse CD3, anti-mouse CD4, anti-mouse
      CD8, anti-mouse CD19, anti-mouse CD152, anti-mouse pan natural killer (NK), anti
      mouse CD80 monoclonal antibodies and expression of surface markers was evaluated
      by flow cytometry. In the serum samples of the mice, the levels of tumor necrosis
      factor alpha (TNF-alpha), interferon gamma (IFN-gamma), transforming growth
      factor-1beta (TGF-1beta), and interleukin (IL)-4, IL-10, and IL-12 cytokines were
      determined by ELISA method. The expressions of all the surface markers of
      lymphocyte evaluated were statistically significantly lower in the infected mice
      than in the healthy control mice (p < 0.05). However, except for the level of TGF
      1beta, the levels of all the other cytokines evaluated were statistically
      significantly higher in the infected group than in the control group (p < 0.001).
      No significant differences were determined between the TGF-1beta levels of the
      study and control groups (p > 0.05). In this study, T, B, and NK lymphocyte
      responses were inhibited and cytokine profiles changed in the course of malarial
      infection. Thus, interventions to increase the Th1 lymphocyte response may be
      beneficial in the prevention of malarial infection.

PMID- 19845112
TI  - Phages specific for mycobacterial lipoarabinomannan help serodiagnosis of
      tuberculosis.
AB  - This study evaluated the possibility to use six phages specific to the
      Mycobacterium tuberculosis lipoarabinomannan (LAM) as tools for tubercular
      serodiagnosis. We analysed sera samples from 30 subjects with active tuberculosis
      (TB+), 30 with latent tubercular infection (LTBI) and 60 healthy subjects as
      controls (K). Our data indicated a good antibody response of the TB+ and LTBI
      patients against the phage Ri(7)17; the optical density (OD) values obtained from
      sera patients was statistically significant when compared to the control samples.
      Our results confirm that phage display technology might be useful to develop new
      tools for diagnosis of tuberculosis.

PMID- 19845113
TI  - Human metapneumovirus infection in a cohort of young asymptomatic subjects.
AB  - Human metapneumovirus (HMPV) is a recently described cause of respiratory
      infection. The purpose of this study was to to further the available information
      on the circulation of HMPV among young asymptomatic subjects. The epidemiology of
      HMPV was examined in a cohort of 73 university students during a winter season by
      using polymerase chain reaction. HPMV was detected in 3/73 (4.1%) asymptomatic
      subjects. Phylogenetic analysis has shown that circulating viruses belonged to
      different HMPV sublineages. Our findings indicate that asymptomatic carriage of
      HMPV might be a neglected source of viral transmission in the community.

PMID- 19845115
TI  - Methicillin-resistant coagulase negative staphylococci isolated from horses.
AB  - A methicillin-resistant (MR) Staphylococcus epidermidis strain was isolated from
      a saddle horse affected by osteolysis. MR coagulase-negative staphylococci
      (MRCNS) were isolated from 11 of 14 (78.8%) horses housed in the same riding
      club. By typing of the SCCmec region, almost the strains displayed a non typeable
      (NT) pattern and possessed the ccr type 2. Altogether, the high prevalence of
      MRCNS and the detection of NT SCCmec types support the hypothesis that horses may
      represent a reservoir of MRCNS for humans and that equine MRCNS may act as
      potential source of resistance genes for other staphylococci.

PMID- 19845114
TI  - Detection of the microbial patterns in a cohort of infants admitted to neonatal
      intensive care.
AB  - Newborn babies admitted into the neonatal intensive care unit (NICU) often
      require many supportive invasive devices and frequently receive antimicrobial
      therapy. We investigated the microbial flora in NICU patients reporting the
      distribution of infections in different catheter sites. Results showed that 97%
      of samples were positive; in particular 11% were positive for two or more
      microbial agents. Coagulase negative Staphylococci were the most commonly
      isolated. The detection of Gram-negative bacteria and yeasts suggested that these
      microorganisms are also involved in infections of hospitalized infants. Finally,
      no correlation between a specific microbial agent and a particular catheter type
      was found.

PMID- 19845116
TI  - Acute respiratory distress syndrome associated with HHV-7 infection in an
      immunocompetent patient: a case report.
AB  - The association of human herpesvirus-7 with lung diseases is poorly known,
      although it has been suggested a role in causing interstitial pneumonia in non
      transplant patients and bronchiolitis-obliterans-organizing-pneumonia in lung
      transplant. No case of acute respiratory distress syndrome associated to human
      herpesvirus-7 has been reported, while only one case associated with human
      herpesvirus-6 has been described in an immunocompetent patient. This report
      describes the identification of human herpesvirus-7 reactivation in an
      immunocompetent patient with acute respiratory distress syndrome, as evidenced by
      the increasing viral load in bronchoalveolar lavage, polyneuropathy,
      histopathological findings, and tissue positivity. Human herpesvirus-7
      reactivation in this context could be a consequence of the tissue damage due to
      the underlying lung disease, rather than the cause, as suggested by the temporal
      profile of viral load on BAL.

PMID- 19845117
TI  - Streptococcus pneumoniae meningitis in a child vaccinated with pneumococcal
      heptavalent conjugate vaccine.
AB  - Pneumococcal meningitis is still today a life threatening disease among children
      under-5 worldwide. Although the heptavalent vaccine has demonstrated its ability
      to reduce the incidence of pneumococcal disease its efficacy is limited due to
      the restricted number of serotypes included. We report a case of a child with a
      Streptococcus pneumoniae meningitis despite the use of heptavalent conjugate
      vaccine.

PMID- 19845118
TI  - Unbalanced nutrition might change the clinical picture of endocrine diseases.

PMID- 19845119
TI  - Pharmacological and physiological growth hormone stimulation tests to predict
      successful GH therapy in children.
AB  - Although the current use of growth hormone (GH) stimulation tests (GHSTs) is
      still subject to debate, the tests are widely used to diagnose GH deficiency.
      This literature review evaluates primarily the sensitivity, specificity and
      reliability of GHSTs and secondarily their convenience. Single pharmacological
      tests typically address only a single pathway in the complex physiological
      regulation of GH secretion and are therefore characterized by lower sensitivity,
      specificity and reliability than combined pharmacological tests or physiological
      tests. In spite of the high levels of sensitivity, specificity and reliability,
      physiological tests require considerably more effort to perform, from the
      physician as well as from the child. Therefore, a need for an alternative,
      convenient, physiological GHST still remains. Oral ingestion of dietary protein
      is convenient in practice and may induce more physiological stimulation of GH
      secretion, hence may be a promising valuable addition to the existing GHSTs in GH
      deficiency.

PMID- 19845120
TI  - Insulin sensitivity in prepubertal Caucasian normal weight children.
AB  - BACKGROUND: Determining whether or not a child is insulin resistant is becoming a
      matter of fundamental interest even in childhood, as the incidence of metabolic
      complications of insulin resistance is rising. Thus reference values are needed.
      AIM: To set percentiles for HOMA-IR and WBISI in Caucasian normal weight
      prepubertal children. POPULATION: 238 normal weight prepubertal Caucasian
      children (126 males/112 females). METHODS: After physical examination including
      anthropometric measurements all children underwent an oral glucose tolerance test
      from which HOMA-IR and WBISI were calculated. RESULTS: HOMA-IR values above the
      95th percentile (2.03) and WBISI values below the 5th percentile (5.67) represent
      the cut-off values for the determination of insulin resistance. CONCLUSION: These
      reference values are useful to easily detect insulin resistance within the
      prepubertal Caucasian population representing a helpful tool for clinicians to
      target such children in order to improve insulin sensitivity.

PMID- 19845121
TI  - Prevalence of metabolic syndrome in schoolchildren and adolescents in Turkey: a
      population-based study.
AB  - AIM: To determine prevalence of the metabolic syndrome (MS) in the pediatric
      population. METHODS: We studied 2,491 schoolchildren randomly selected aged 10-19
      years using a multistage, stratified sampling design. Obese and overweight
      participants were called for further investigation (n = 456). Of these, 310
      participants underwent OGTT. MS was defined according to IDF, NCEP and modified
      WHO guidelines. RESULTS: The prevalence of obesity and overweight were 6.8% and
      11.5%, respectively. While MS was found in 2.3% of the total population according
      to IDF guidelines, its prevalence was increased among overweight and obese
      individuals. MS prevalence was similar by both IDF and NCEP definitions but
      higher according to WHO definition. Individuals with MS were consistent by both
      IDF and NCEP definitions (sensitivity = 100%, specificity = 99%, positive
      predictive value = 95.2%). IDF and WHO defined different individuals as having MS
      (sensitivity = 67.5%, specificity = 90%, positive predictive value = 67.5%).
      CONCLUSIONS: Although not as high as in developed countries, MS prevalence
      determined in schoolchildren and adolescents in Turkey warrants preventive
      measures. MS diagnosis in one of every three obese children shows that MS is an
      important public health problem in Turkey as well.

PMID- 19845122
TI  - Longitudinal pubertal growth according to age at pubertal growth spurt onset:
      data from a Spanish study including 458 children (223 boys and 235 girls).
AB  - BACKGROUND: Age at pubertal growth spurt (PGS) onset varies and is sex-dependent.
      We present anthropometric pubertal growth data for five 1-year interval age
      maturity groups: very early, early, intermediate, late and very late. METHODS:
      Longitudinal growth study of 458 healthy children (223 boys, 235 girls). Ages at
      PGS onset and at adult height attainment, total pubertal growth (TPG), and peak
      height velocity (PHV) were evaluated. PGS begins between the ages of 10 and 15 in
      boys and 8 and 13 in girls; children were allocated to the corresponding 1-year
      interval age maturity group. RESULTS: For each sex, the earlier the start of PGS
      onset, the higher were PHV and TPG gain. However, adult heights were similar
      among the five pubertal maturity groups. Height SDS values for mean values of the
      very early, early, late and very late maturity groups calculated according to
      data from the five pubertal maturity groups taken together as a single group
      differed from zero in both sexes, mainly during the pubertal years for the very
      early (> +1) and very late (> -1) maturers. These differences disappeared at
      adult height. CONCLUSIONS: Our data might contribute to better clinical
      evaluation of pubertal growth according to individual pubertal maturity tempo.

PMID- 19845123
TI  - Body composition of white and black Brazilian schoolchildren.
AB  - AIM: To evaluate body composition of black and white schoolchildren in Brazil.
      METHODS: The study included 1,443 children aged 6-11 years, both genders, black
      and white skin colors. The measures of weight, height, BMI, brachial perimeter,
      tricipital and subscapular skinfolds, lean and fat area of the arm were
      transformed into standard deviation scores (SDS). RESULTS: As to frequency of
      variables under -2 SDS, only arm perimeter and lean area of the arm in both white
      and black schoolchildren showed results over 7%, but tricipital and subscapular
      skinfolds, fat area of the arm, sum of skinfolds and fat percentage, in both skin
      colors, presented results close to zero. As to frequency of variables over +2
      SDS, only fat percentage presented results over 5% in both skin colors.
      CONCLUSION: The present study did not find important differences in body
      composition between black and white schoolchildren in this group of the Brazilian
      population.

PMID- 19845124
TI  - Growth factors, inflammatory cytokines and postnatal bone strength in preterm
      infants.
AB  - AIM: To assess the relationships between growth factors, inflammatory cytokines
      and postnatal bone development in preterm infants. METHODS: Fifty premature
      infants (24-32 weeks gestational age, mean birth weight: 1,024 +/- 50 g)
      participated in the study. Bone strength was determined weekly by quantitative
      ultrasound measurements of bone speed of sound (SOS). Blood serum measurements of
      growth factors included circulating IGF-I and GH binding protein. Measurements of
      circulating cytokines included the pro-inflammatory mediator interleukin (IL)-6,
      and the anti-inflammatory mediator IL-1 receptor antagonist. Samples were
      collected when the preterm infants were stabilized and prior to discharge.
      RESULTS: Despite a significant increase in body weight (from 1,024 +/- 50 to
      2,420 +/- 59 g, p < 0.001) and body length (from 35.4 +/- 0.6 to 44.6 +/- 0.4 cm,
      p < 0.001) there was a significant decrease in bone SOS during the follow-up
      period. There was a significant increase in growth factors and a decrease in
      inflammatory cytokines during the follow-up. Participants were divided into
      preterm infants who increased bone SOS (bone gainers, n = 16, from 2,867 +/- 38
      to 2,910 +/- 41 m/sec), or decreased bone SOS (bone losers, n = 34, from 2,967 +/
      33 to 2,818 +/- 28 m/sec) during follow-up. Baseline bone SOS was significantly
      lower in the bone gainers. Baseline circulating growth factors were higher and
      inflammatory cytokines lower in the bone gainers; however, only the difference in
      IL-6 reached statistical significance (6.4 +/- 1.6 versus 10.5 +/- 1.2 pg/ml, in
      bone gainers and losers, respectively; p < 0.05). CONCLUSIONS: Preterm infants
      with lower bone SOS at birth tend to 'catch-up' during early postnatal weeks.
      Increases in bone strength in preterm infants were associated with reduced
      inflammatory state as suggested by lower levels of circulating IL-6.

PMID- 19845125
TI  - Cinacalcet for hyperparathyroidism in pregnancy and puerperium.
AB  - The efficacy and safety of various modes of medical treatment for primary
      hyperparathyroidism (PHPT) in pregnancy is largely unknown. This report describes
      two cases of PHPT in pregnancy that were temporarily treated with the
      calcimimetic cinacalcet. The first case was diagnosed in the 31st week of
      pregnancy. The patient was asymptomatic and had an albumin-corrected total
      calcium level (Ca(corr)) of 3.24 mmol/l. As serum calcium was only mildly
      elevated it was decided to postpone surgery to the postpartum period. Cinacalcet
      was started immediately after delivery to prevent a postpartum surge in serum
      calcium. The second patient presented with hypertension and symptomatic
      hypercalcemia (Ca(corr) 3.96 mmol/l) in the 32nd week of pregnancy. Surgery was
      postponed because of suspected pheochromocytoma. Treatment with a combination of
      cinacalcet and calcitonin reduced serum Ca(corr) to 3.0 mmol/l. This report
      describes the monitoring of mother and child, and explores the pros and cons of
      the use of calcimimetics during pregnancy and puerperium.

PMID- 19845126
TI  - A case of premature thelarche with no central cause or genetic variants within
      the estrogen receptor signaling pathway.
AB  - BACKGROUND: Premature thelarche is defined as breast development before 8 years
      of age. This is most often caused by central hormone disregulation and is
      accompanied by concurrent bone maturation. However, we present a case of
      premature thelarche with concurrent bone maturation without central hormone
      disregulation. Genes within the estrogen signaling pathway were examined for
      genetic changes which might be responsible for the clinical phenotype. PATIENT
      REPORT: A girl presented with breast development from 18 months of age with
      undetectable serum estrogens, prepubertal serum gonadotropins, advanced growth
      and skeletal maturation, but no increase of uterine size, thus presenting a
      premature thelarche variant. Serum estrogens remained below detectable limits
      until she entered into an unremarkable puberty at 12.1 years of age. No
      abnormalities or SNPs were found in the genes tested. CONCLUSION: We describe a
      case of premature thelarche which cannot be attributed to a central cause of
      abnormal hormone levels or to alterations in genes suspected for this phenotype.
      We conclude that other yet to be identified factors are involved in this unique
      case of premature thelarche.

PMID- 19845127
TI  - Diagnosis of small bowel telangiectasia in Turner's syndrome using capsule
      endoscopy.

PMID- 19845128
TI  - Zolendronate in osteogenesis imperfecta.

PMID- 19845129
TI  - Compensation for the effect of soft tissue artefact on humeral axial rotation
      angle.
AB  - Soft tissue artefact (STA) is caused by the relative displacement of markers or
      sensors mounted on the skin surface with respect to the underlying bones, and is
      a major source of error in the kinematic measurement of human movement. In
      particular, the humeral axial rotation (HAR) is affected by STA. The aim of this
      study was to propose a method for compensating for STA and to validate its
      effectiveness. In the proposed method, the HAR angle was calculated by a second
      order regression using three independent variables converted from the Cardan
      angles of the shoulder joint. The calculated HAR angle (HAR-r) was compared with
      the angle calculated from the direction of the longitudinal axis of the forearm
      (HAR-f). Highly linear correlations were found between HAR-r and HAR-f when the
      elbow joint was flexed at 90 degrees. The elbow flexion/extension motion had
      little influence on the HAR-r, whereas HAR-f became unstable when the elbow joint
      approached its full extension. Because HAR-r effectively compensates for the STA
      and is independent of the elbow flexion/extension, the regression method is
      suitable for the movement analysis of the upper limbs.

PMID- 19845130
TI  - Elemental analysis of inorganic dusts in lung tissues of interstitial pneumonias.
AB  - People have the opportunity to inhale inorganic dusts under various environments.
      Inorganic dust exposures as a result of occupational exposure may induce or
      modulate pulmonary fibrosis. We analyzed the deposition of elements in lung
      tissues of patients with idiopathic pulmonary fibrosis (IPF) and compared element
      deposition with chronic hypersensitivity pneumonitis (chronic HP) and collagen
      vascular diseases (CVD). Thirty-five patients (18 men and 17 women with the mean
      age of 64.3) were studied, including 15 IPF, 8 chronic HP, 6 CVD, and 6 control
      patients. Four IPF patients have occupational dust exposures. Inorganic particles
      were counted by polarizing light microscopy and scanning electron microscopy.
      Energy dispersive X-ray spectroscopy was performed to analyze an elemental
      deposition. The number of birefringent particles was greater in IPF, even in IPF
      without occupational exposure, than in controls. The silicon (Si)/sulfur (S)
      ratio and aluminium (AI)/S ratio were increased in IPF independent of
      occupational exposure. A point elemental analysis showed that the major compound
      of the particles was aluminium-silicate in IPF. These results suggest that
      unrecognized dust exposures are relatively common in some IPF patients and
      aluminium-silicate could be associated with the disease process of IPF.

PMID- 19845131
TI  - In vitro study of reduction of stress transferred onto tissues around implants
      using a resilient material in maxillary implant overdentures.
AB  - The purpose of this in vitro study was to investigate the effect of hardness on
      the reduction of stress transferred to tissues around implants using a resilient
      material applied to the female parts of the ball attachment in maxillary implant
      overdentures. A cast chrome-cobalt framework was mounted onto a maxillary acrylic
      edentulous model, which contained two implants and four strain gauges attached to
      the implant. Ball abutments were screwed into the implant. One abutment was
      connected to a dedicated metal cap embedded in the housing, while the others were
      connected to resilient test materials with four different hardnesses. Loads were
      applied using a universal testing machine with a magnitude of 50 N. The sums of
      the absolute values recorded from the four strain gauges were used for stress
      evaluation. The measured strains were analyzed statistically using two-way ANOVA
      and multiple comparisons. A resilient material with hardness 90 exhibited strains
      that did not differ significantly from the control. In contrast, the other
      resilient materials showed significantly reduced strains under all conditions. In
      this limited study, application of resilient silicone materials with approximate
      hardness 80 to the female parts of ball attachments significantly reduced the
      stress on the tissues around the implant.

PMID- 19845132
TI  - Cortical activation during solid bolus swallowing.
AB  - Specific areas of cortical activity during solid bolus swallowing in humans are
      unknown. We tested the hypothesis that cortical representations of swallowing in
      humans may vary by bolus type. Twenty-one normal subjects swallowed three kinds
      of food: agar (solid), a capsule and water. We followed the same countdown method
      for identification of the cortical representations during swallowing performances
      as a previous study (Tanaka et al., 2006). Functional magnetic resonance imaging
      (fMRI) showed that the precentral gyrus, postcentral gyrus, medial temporal
      gyrus, superior temporal gyrus and cingulate gyrus were activated when swallowing
      an agar bolus (p<0.001). The subcortex was not activated. The cerebellum was
      activated only during capsule swallowing (P<0.001). Water bolus swallowing
      activations were similar to agar bolus swallowing. The cluster size of water
      swallowing was larger than the agar swallowing. We conclude that the cortical
      representations for swallowing are variable by food type.

PMID- 19845133
TI  - Periodontal masseteric reflex is changed by periodontal sensory modification
      during occlusal hypofunction in rats.
AB  - The purpose of this study was to investigate changes in the periodontal
      masseteric reflex (PMR) after experimentally induced occlusal hypofunction.
      Wistar rats were divided into control groups (CGs) and hypofunction groups (HGs).
      Rats in the HGs had their lower incisors cut down every other day for 6 weeks.
      Electrical stimulation was given to the periodontal ligaments of an upper incisor
      or the left trigeminal mesencephalic nucleus (MeV) in the CGs and HGs. Recordings
      of masseter motor unit responses were performed at 0, 1, 2, 4 and 6 weeks after
      hypofunction. Compared with the CGs, significant longer latencies in the PMR were
      found in the 4w- and 6w- HGs. After MeV stimulation, no significant difference in
      latency was found between HGs and CGs. After periodontal stimulation, the
      threshold value of masseteric motor-unit responses was higher in HGs than in CGs
      in 4and 6 weeks respectively. These results suggest that the PMR can be changed
      by periodontal sensory modification during occlusal hypofunction.

PMID- 19845134
TI  - The prevalence of co-morbid depression among employees with type 2 diabetes in a
      Japanese corporation: a descriptive study using an integrated health database.
AB  - OBJECTIVE: To determine the prevalence of comorbid depression among people with
      type 2 diabetes using the integrated health database. METHODS: A total of 6543
      people aged 18-65 years were selected from the employees of a Japanese
      corporation. Using the corporation's integrated health database, which consisted
      of medical claims data and a self-reported questionnaire from the fiscal year
      2000, this study was undertaken to identify the prevalence, the odds ratio and
      some related factors. RESULTS: The prevalence of co-morbid depression among
      people with type 2 diabetes was 2.6%. The crude odds ratio of co-morbid
      depression among those with type 2 diabetes was 2.20 (95% CI 0.88-5.50). After
      adjustment for covariates (gender, age, alcohol drinking, smoking, exercise, and
      dietary restriction), the odds ratio of co-morbid depression among those with
      type 2 diabetes was 2.33 (0.86-6.33). CONCLUSIONS: Using the integrated health
      database, it was suggested that patients with type 2 diabetes were more likely to
      suffer from depression and there was a relationship between depression and
      dietary restriction of portion control.

PMID- 19845135
TI  - Effects of occlusal loading on alveolar bone remodeling and changes in the
      distribution of neuropeptides after tooth replantation in rats.
AB  - Biomechanical and biochemical factors are involved in bone remodeling. Occlusal
      loading is a well-known mechanical modulator of alveolar bone remodeling.
      Neuropeptides, such as vasoactive intestinal peptide (VIP) and calcitonin
      generelated peptide (CGRP), have been described within the biochemical bone
      regulators. In this study, the influences of occlusal loading on the alveolar
      bone remodeling and the distribution of VIP- and CGRP-immunoreactive (IR) fibers
      were investigated 1, 3 and 5 days after tooth replantation in rats. At day 5,
      occlusal loading induced a significant increase (p<0.05) in osteoclast number and
      osteoblast surface compared to those in the nonoccluded group. VIP-IR fibers were
      observed beside osteoblastic layers and their distribution was significantly
      enhanced (p<0.05) at day 5 in the occluded group, compared to the non-occluded
      group. Although there was immunoreactivity for CGRP in the periodontal ligament
      and alveolar bone apically, CGRP-IR fibers were not detected above the furcation.
      These results suggest that, after tooth replantation in rats, occlusal loading
      induced an increase in osteoclast and osteoblast formation, and that VIP might
      play a functional role in osteoblasts.

PMID- 19845136
TI  - What factors are affecting physician payment by acute care hospitals in rural
      Japan?
AB  - The regional discrepancies of physician supply have been a growing concern in
      Japan. To find out how hospitals are responding in terms of physician payment (by
      monthly salaries and additional benefits), we conducted a survey of acute care
      hospitals in Yamagata, Japan. We asked about the salary and additional benefits
      of full-time physicians and the structural and functional characteristics of
      health care service provision. From these data we set out to assemble a model
      that can explain effectively the variability of physician payment in acute care
      hospitals within the prefecture. We found that physician payment was associated
      with variables such as type of management, staff employed per bed, full time
      doctors employed per bed and average length of stay. Hospital location was found
      to have a significant effect on payment. Variables expressing workload, like
      number of in-patients per doctor and number of surgical operations per doctor
      were inversely related. Our results suggest that hospitals may have adapted to
      physician preferences of workplace in terms of physician payment. To further
      address the problems of unbalanced geographic distribution of physicians in rural
      areas, work-sharing and educational and technical support schemes may also help.

PMID- 19845137
TI  - Evaluations of masticatory performance of complete denture wearers using color
      changeable chewing gum and other evaluating methods.
AB  - We have been investigating and developing a color-changeable chewing gum, that
      tends not to adhere to dentures. The aim of this study was to investigate the
      color change of the chewing gum comparing to other methods while evaluating post
      insertion changes of masticatory performance of complete denture wearers. Color
      changeable chewing gum, the peanuts sieve test, a patient satisfaction
      questionnaire and a food questionnaire were applied to 26 edentulous subjects.
      The subjects were tested on two occasions: with previous dentures, with new
      dentures when they had no symptoms after finishing denture adjustment. In
      comparison between the differences of previous and new dentures, significant
      correlations were found between the color change of the chewing gum and the
      scores of patient satisfaction questionnaires and food questionnaire. It was
      suggested that this chewing gum was useful for an objective masticatory
      evaluation of the denture wearers and could contribute to prosthetic treatments
      according to patients' satisfaction for dentures, which is clinically important
      information for both patients and dentists.

PMID- 19845138
TI  - Occlusal stimuli regulate interleukin-1 beta and FGF-2 expression in rat
      periodontal ligament.
AB  - While many studies reported the structural changes in the periodontal ligament
      (PDL) under hypofunctional conditions, the associations of cytokine growth
      factors are still unclear. They are known to take part in inflammation, and may
      affect the biological properties of hypofunctional tooth. To investigate the
      hypofunctional PDL and the recovery from this condition, we focused on
      interleukin-1 beta (IL-1beta) and basic fibroblast growth factor (FGF-2). Male
      Wistar rats were divided into occluded, non-occluded, and recovery groups. An
      anterior bite plate was used to eliminate the occlusal contact of molars in the
      non-occluded group, and was then removed for the recovery group. After occlusal
      stimuli were eliminated for 7 and 14 days, and after 3 and 7 days of recovery
      from 7 days in the hypofunctional condition, the PDLs of the lower first molars
      were investigated immunohistochemically. The lack of occlusal stimuli caused
      atrophic changes in the PDL with the upregulation of IL-1beta and decreased
      expression of FGF-2, while decreased IL-1beta and enhanced FGF-2 expression were
      observed in the recovery process. These results suggest that occlusal stimuli
      regulate IL-1beta and FGF-2 expression, and the nature of this regulation may
      differ from that in the healing process of an inflammatory reaction.

PMID- 19845139
TI  - Influence of estrogen cycle on temporomandibular joint synovial membrane in rat
      with deviated mandible.
AB  - Temporomandibular disorders (TMD) are known to be more prevalent and severe in
      women than in men, especially in those who are in their reproductive age. In
      those patients reproductive hormones may play a vital role in the host adaptive
      capacity of the temporomandibular joint (TMJ). In order to clarify the
      relationship between TMD prevalence and estrogen cycle, a mandible deviated
      animal model was carried out, and the expression of inducible nitric oxide
      synthase (iNOS), an essential enzyme in the pathogenesis of inflammatory
      arthritis, was investigated in the rat's synovial tissue. An appliance was
      attached to the rat's incisors to produce a lateral deviation of the mandible
      during the metestrus phase, and the animals were sacrificed in the proestrus and
      estrus phase, when the estrogen was at the highest and lowest level,
      respectively. Immunostaining was then performed for 2 consecutive estrous cycles
      to demonstrate iNOS expression in the synovial membrane of the TMJ. The
      immunoreactivity for iNOS was more intense in the synovial membrane on the
      contralateral side in the proestrus phase (estrogen peak phase). These
      observations suggest that iNOS expression in the synovial membrane with
      mandibular deviation may be exacerbated in the presence of estrogen.

PMID- 19845140
TI  - Effect of cigarette smoking on the development of murine chronic pigeon breeder's
      lung. The difference between a short-term and a long-term exposure.
AB  - Previous reports suggested that cigarette smoke had a protective effect of on the
      development of hypersensitivity pneumonitis (HP). However, smoking rate in
      chronic pigeon breeder's lung (PBL) seemed to be high in our clinical
      experiences. We developed a murine model of PBL by intranasal instillation with
      pigeon dropping extracts (PDE) for 4 weeks (short-term exposure) and 17 weeks
      (long-term exposure) to investigate the effect of cigarette smoke on disease
      processes. In this model, lung inflammation associated with the production of
      anti-PDE antibodies and antigen dependent lymphocyte proliferation was induced.
      Long-term exposure to PDE without cigarette smoking resulted in an increase in
      lung weight/body weight ratio, total cell number in bronchoalveolar lavage (BAL)
      fluid, and content of hydroxyproline in the lung compared to shortterm exposure.
      After a short-term exposure, cigarette smoke lessened the lymphocytosis in BAL
      fluid, and lymphocyte proliferation. On the other hand, after a long-term
      exposure cigarette smoke increased lung hydroxyproline. These results suggest
      that a short-term cigarette smoking attenuates lung inflammation, but a long-term
      cigarette smoking enhances lung inflammation with fibrosis.

PMID- 19845141
TI  - High glucose concentrations impair the activation of K+ channels and proteases in
      undifferentiated THP-1 monocytes.
AB  - Transient alkalization caused by activation of the BK(Ca) channels has been
      reported to be essential for the activation of proteolytic enzymes and bacterial
      killing in the leukocytic phagosomes. We investigated the effects of high glucose
      concentrations on these processes in THP-1 cells. While E. coli transiently
      raised the pH of the phagosomes in THP-1 monocytes, high glucose concentrations
      impaired the transient rise of pH in a dose-and time-dependent manner.
      Electrophysiological studies confirmed that the bacteria elicited a transient K+
      current, and that a high glucose concentration diminished the current. High
      glucose concentrations also inhibited the activation of cathepsin G in the THP-1
      cells. NS1619, a BK(Ca) channel opener, accentuated the transient alkalization
      induced by the bacteria, and reversed the inhibitory effect of high
      concentrations of glucose. However, electrophysiological study revealed that the
      membrane current differed from the BK(Ca) current. Our findings indicate that
      high glucose concentrations impair K+ channel activation and the subsequent
      activation of proteolytic enzymes in THP-1 monocytes. The precise identity of the
      K+ channel remains unclear, although it dose not appear to be the BK(Ca).
      Suppression of the transient alkalization and activation of proteases may be one
      of the mechanisms for bacterial killing by phagocytes in diabetic patients.

PMID- 19845142
TI  - The fundamental properties of Homer 1 in association with cardiac ryanodine
      receptor in mouse heart.
AB  - BACKGROUND: Homer, known as a scaffolding protein that regulates postsynapse
      signaling in neurons, has been poorly explored in cardiac research. We show the
      fundamental properties of Homer 1 in mouse heart in association with cardiac
      ryanodine receptor (RyR), a binding protein of Homer 1. METHODS AND RESULTS:
      Immunohistochemistry of adult mouse heart with Homer 1 antibody showed striated
      staining on Z-bands both in atria and ventricles. The interactions between Homer
      1 and RyR were confirmed by co-immunoprecipitation assays. Immunostaining of
      adult isolated cardiomyocytes showed partial co-localization of both proteins. In
      neonatal primary cultures, targeting of Homer 1 preceded that of RyR in their Z
      band arrangement. CONCLUSIONS: Homer 1 binds to RyR in adult mouse heart and
      precedes RyR in Z-band arrangement in the early postnatal period.

PMID- 19845143
TI  - TGF-beta and glutathione promote tissue repair in cigarette smoke induced injury.
AB  - We studied the effect of cigarette smoke extract (CSE) on a three-dimensional (3
      D) co-culture model with epithelial cells and mesenchymal cells to clarify how
      epithelial cells protect lung tissue from cigarette smoke in-vivo. Two types of
      gels were prepared. The one was the co-culture of human fetal lung fibroblasts
      (HFL-I) embedded in type-I collagen gel, with alveolar epithelial cells (A549)
      cultured covering the top of the gel. The other was HFL-I cells alone. After 48
      hours from CSE exposure, gel contraction, levels of fibronectin, transforming
      growth factor (TGF)-beta and GSH were assessed. CSE inhibited fibroblast-mediated
      gel contraction and this inhibition was lessened in co-culture associated with
      higher GSH concentration and TGF-beta1 level as compared to the level in HFL-I
      cells alone. CSE lowered fibronectin level to a lesser extent in co-culture as
      compared to the level in HFL-I cells alone. Exogenous TGF-beta1 restored the
      inhibition of gel contraction by CSE independent of GSH level. Cigarette smoke
      may interfere with 3-D co-culture gel contraction by diminishing GSH, fibronectin
      and TGF-beta1 action in the epithelial-mesenchymal interaction.

PMID- 19845144
TI  - The effects of various finishing materials on the gloss and the color change of
      indirect prosthetic resin composites.
AB  - The effect of different polishing materials on the surface texture and the color
      change of indirect prosthetic resin composite materials exposed to a staining
      agent was studied. Six different resin composites were polished using the same
      procedures and were measured for the gloss. After exposed to a coffee solution,
      the changes were measured on the color properties. The six different types of
      resin composites were further divided into four groups of eight specimens each
      for the different surface polishing procedure. The gloss was measured by a gloss
      meter (TC-108D, Tokyo-Densyoku, Tokyo, Japan) with an angle of 45 degrees and
      expressed in gloss units (GU). Before and after exposure to the staining agent,
      the color measurements of all specimens were recorded with a colorimeter (TC
      1800MKII, Tokyo-Densyoku, Tokyo, Japan) using CIE L* a* b*. All specimens were
      stored in the coffee solution for 5 weeks at 37 degrees C. Most of the resin
      composites showed the highest gloss and staining resistances when the fine
      silicone diamond polishing point was used. The results of this study suggested
      that there are differences in the gloss and the color changes depending on the
      filler type and the composition of the polishing materials.

PMID- 19845145
TI  - Impact of routine oral care on opportunistic pathogens in the institutionalized
      elderly.
AB  - Routine oral hygiene is important for the control of opportunistic pathogens in
      the oral cavity of institutionalized elderly individuals. We evaluated the
      effects of routine oral care on opportunistic pathogens at various time points
      after admission to a nursing home. Twenty-five elderly subjects living in the
      nursing home (mean age: 86.0 +/- 10.4 years) participated in the study.
      Caregivers and dental hygienists cleaned the teeth, dentures, tongue, and mucosa
      after each meal using both routine and professional oral care techniques.
      Opportunistic pathogens were collected from the teeth, tongue, and mucosal
      surfaces using a cotton swab; and the species of microbes were determined and the
      numbers were counted following cultivation on selective agar. Regular oral care
      including professional oral care was found to be effective for reducing
      infections by many kinds of opportunistic pathogens on the teeth surfaces and the
      oral environment without food residue during a long-term study (6 months).
      Further, this care after 1 month significantly reduced infections by
      opportunistic pathogens on mucosal surfaces in subjects without dentures;
      however, this was not observed in those with dentures. Our data shows the
      importance of regular oral care in cleaning hard and soft surfaces of the oral
      cavity improves the oral health of the institutionalized elderly.

PMID- 19845146
TI  - Pentazocine transport by square-wave AC iontophoresis with an adjusted duty
      cycle.
AB  - So far, pentazocine iontophoresis has never been studied, although pentazocine is
      widely used in pain management. The purpose of this study was to determine
      whether pentazocine transportation through a cellophane membrane could be
      enhanced using square-wave alternating current (AC) iontophoresis with an
      adjusted duty cycle and dependence on the voltage and the duty cycle. Voltages of
      10, 25 and 40 V with duty cycles of 50%, 51%, 52%, 53%, 54% and 55% were applied
      for 60 minutes at a high frequency of 1 MHz to diffusion cells on both sides of a
      cellophane membrane. The donor compartment was filled with a solution containing
      pentazocine. Square-wave AC iontophoresis with an adjusted duty cycle enhanced
      pentazocine transportation at higher voltages and duty cycles. These results
      suggested that the direct current (DC) component of the square-wave AC played an
      important role in enhancing pentazocine transportation despite changes in
      polarity at very high frequency of 1 MHz. The higher voltages and duty cycles
      induced a pH change. The practical electrical conditions that could be applied
      clinically were 25 V with a 54% duty cycle or 40 V with a 53% duty cycle.

PMID- 19845147
TI  - Immunohistochemical localization of phospholipase A2 in the guinea pig nasal
      mucosa.
AB  - OBJECTIVE: Phospholipase A2 (PLA2) is a key enzyme in arachidonic acid
      metabolism, which is involved in the maintenance of biological homeostasis and
      the onset of various diseases. The immunohistochemical localization of PLA2 in
      the nasal mucosa has not been reported, even though the presence of messenger RNA
      of PLA2 has been demonstrated in the human nasal brush sample. The present study
      was designed to determine the localization of PLA2s in the nasal cavity. METHODS:
      The immunohistochemichal localization of secretory PLA2 (sPLA2) and cytosolic
      PLA2 (cPLA2) in the nasal mucosa was studied using adult guinea pig. RESULTS:
      Both sPLA2 and cPLA2 were localized in the nasal gland as well as the respiratory
      epithelium, and not in the surrounding vascular endothelial cells, olfactory
      gland, olfactory epithelium or submucosal tissue. CONCLUSION: Our data provide
      the first convincing evidence that both sPLA2 and cPLA2 are significantly
      expressed in the nasal gland and the respiratory epithelium, and are suggested to
      regulate the function of the nasal mucosa, such as bactericidal, Na secretion,
      and allergic response.

PMID- 19845148
TI  - Safe patient transfer system with monitoring of location and vital signs.
AB  - In recent years, ubiquitous computing technologies have been applied in the field
      of medicine. Especially radio frequency identification (RFID) and small sensor
      networks could provide information about medical practices and patient status in
      order to prevent malpractices and improve the quality of medical care. As an
      example of this application, we developed a new system, named "a smart
      stretcher," which continuously monitors the patient's vital signs and detects
      apnea during transfer within a hospital. This system consists of a small air-mat
      type pressure sensor measuring both heart rate and respiration rate and a
      wireless network transmitting these vital data as well as patient ID to an
      alerting system to notify hospital staff of patient emergencies. Results of
      experiments in a clinical setting indicated that the system was reliable in
      continuous respiration monitoring and detection of apnea during patient transfer
      on the stretcher; however, detection of heartbeat rate was practically difficult
      because of the motion noises. Moreover patient ID and location were also
      correctly detected in real time. These results suggested the feasibility of our
      system for real clinical use.

PMID- 19845149
TI  - Overweight patients with severe sleep apnea experience deeper oxygen desaturation
      at apneic events.
AB  - We investigated differences in the depth of hypoxia produced by apneic events of
      the same duration (30 seconds) amongst patients with different degrees of OSAS
      according to their AIs (apnea indices). The relationship between apnea duration
      (seconds) and fall in oxygen saturation (%) was evaluated by means of a linear
      regression analysis. The fall induced by a 30-second apnea event was designated
      as the "oxygen desaturation value 30" (ODV30). We analyzed the polysomnographic
      recordings of 122 OSAS patients who showed significant correlations (p<0.01)
      between apnea duration and subsequent fall in oxygen saturation and calculated
      their respective ODV30. We evaluated the influence of AI and BMI on ODV30 by
      multi-comparison and found out that standardized partial regression coefficients
      of BMI and AI were 0.578 and 0.148, respectively (multi-regression analysis,
      SPSS). BMI was proved to be more influential on ODV30 than AI was. On the other
      hand, the ODV30 of mild, moderate and severe OSAS patients was 8.84 +/- 2.62%
      (Mean +/- S.D.), 8.25 +/- 2.45% and 10.59 +/- 3.32%, respectively. Our study
      shows that fall in oxygen saturation is particularly extensive in severe OSAS
      patients and that fall in oxygen saturation is deepened as obesity increases. We
      think ODV30 is a useful variable for evaluating OSAS.

PMID- 19845150
TI  - Inhibition of IkappaB kinase beta restrains oncogenic proliferation of pancreatic
      cancer cells.
AB  - PURPOSE: Pancreatic cancer is characterized by an extremely poor prognosis due to
      the aggressive disease course and lack of effective therapeutic intervention.
      IkappaB kinase (IKK), a central kinase for nuclear factor-kappaB (NF-kappaB)
      activation, is often constitutively activated in pancreatic cancer cells, playing
      a crucial role in the malignant phenotype and resistance to anti-cancer agents.
      This study explored how specific inhibition of IKKbeta suppresses oncogenic
      proliferation of pancreatic cancer cells. EXPERIMENTAL DESIGN: We employed two
      different approaches, RNA interference-mediated depletion of IKKbeta (IKKbetai)
      and use of a novel molecularly designed IKKbeta inhibitor IMD-0354 to investigate
      the effects on the in vitro and in vivo growth and apoptotic response of
      pancreatic cancer cells. RESULTS: IKKbetai and IMD-0354 efficiently suppressed
      constitutive NF-kappaB activity and the growth of pancreatic cancer cells in
      monolayer and soft agar. IMD-0354 induced Annexin V expression, a typical
      apoptotic cell response. Notably, daily administration of IMD-0354 significantly
      suppressed tumor growth in NOD/SCID/gamma c(null) (NOG) mice without any
      deleterious side effect. CONCLUSIONS: These results identify IKKbeta as an
      attractive molecular target for pancreatic cancer therapy.

PMID- 19845151
TI  - Age-related changes in oral mechanosensitivity of symptom-free subjects.
AB  - The purpose of this study was to determine the effect of aging on the tactile and
      pain sensitivity, and the factors influencing threshold change in the oral mucosa
      using Semmes-Weinstein Pressure Aesthesiometer. The touch and pain thresholds of
      81 healthy elderly (40 males and 41 females, 77 +/- 4.5 years) were compared with
      those of 58 young volunteers (27 males and 31 females, 27 +/- 2.5 years). We
      measured the pain thresholds, the touch thresholds, PCR score and amount of
      salivation. Semmes-Weinstein Pressure Aesthesiometer was applied to 9 points in
      the oral region and 4 points in the hands; the dorsum manus, the palma manus, the
      incisive papilla, the palatal mucosa, the buccal mucosa, the margin of the
      tongue, and the dorsum of the tongue. Elderly subjects showed significantly
      higher touch thresholds than those of young subjects in the dorsum manus, the
      palma manus, the buccal mucosa, the incisive papilla, the margin of the tongue,
      and the dorsum of the tongue (P < 0.05). The pain thresholds of elderly subjects
      were significantly lower than those of young subjects in the buccal mucosa and
      the palatal mucosa (P < 0.05). The touch threshold was not influenced by the
      smoking habit, denture and amount of salivation. The pain threshold was
      influenced by the denture on the palate.

PMID- 19845152
TI  - The axonal regeneration across a honeycomb collagen sponge applied to the
      transected spinal cord.
AB  - We developed a honeycomb-shaped lyophilized Type I atelocollagen (Honeycomb
      Collagen: HC) with different pore sizes, and the effectiveness of the honeycomb
      shape on nerve regeneration was examined. We analyzed neurite outgrowth of dorsal
      root ganglion (DRG) explants on HC, both in vitro and, with direct implantation
      of HC into the defects of adult rat spinal cords, in vivo. The neurites of DRGs
      on HC extended linearly through the pores. HC with a 400 microm-pore size
      enhanced neurite extension, and YIGSR laminin peptide coating to the HC extended
      more neurites than fibronectin coating. The HC scaffolds coated with YIGSR were
      implanted into 2 mm-defects of spinal cords at the level of T8-9. Four weeks
      after implantation, the implants had degraded and been replaced with self
      tissues, repairing the injured site. Neurofilament-positive fibers were observed
      in the implantation area and passed the borders between the HC and spinal cord
      stumps. Functionally, a motor-evoked potential was observed in the quadriceps
      femoris muscle 10 weeks after implantation. The electrophysiological examination
      showed reconstruction of axon tracts over the implant. This result indicates that
      our developed honeycomb shape is advantageous for host spinal cord compared to
      the random pored sponge shape, and that it promotes axonal regeneration after
      spinal cord injury.

PMID- 19845153
TI  - Comparison of the main occluding area between adults and adolescents.
AB  - It has become clear that foods crushing is performed in the circumscribed region
      between functional cusps, that is, at "the main occluding area". However, it is
      not established to evaluate this area objectively. The purpose of this study was
      to establish the positional evaluation of the main occluding area quantitatively
      and evaluate the positional change depending on the age with this method. The
      subjects were fifteen adults and ten adolescents who had no stomatognathic
      disorder. Temporary Stopping was used as test material in this study. In order to
      analyze the position of the main occluding area, the projected centroid
      coordinate of the test material was calculated and projected onto the reference
      axis. It was possible to quantitatively evaluate positional changes of the main
      occluding area depending on growth process. As a result, the main occluding areas
      of the adults were significantly posterior to those of the adolescents and tended
      to be more stable. There was a significant difference in the occlusal contant
      area between two groups. The occlusal contact area had great influence on the
      stability of the main occluding area. However, besides occlusal contact area,
      there might be other factors which stabilized the main occluding area.

PMID- 19845154
TI  - Effects of pore size and implant volume of porous hydroxyapatite/collagen
      (HAp/Col) on bone formation in a rabbit bone defect model.
AB  - A porous hydroxyapatite/collagen composite (HAp/Col) was developed that consists
      of hydroxyapatite nanocrystals and atelocollagen. In this study, cylindrical
      (diameter: 5 mm, height: 3 mm) porous HAp/Col implants with different pore sizes
      (diameter: 160 or 290 microm) were prepared, and the influences of pore size and
      implanted volume were evaluated using a rabbit bone defect model. In the implant
      groups, one or three (diameter: 5 mm, total height: 9 mm) implants were
      transplanted into bone holes created in the anteromedial site of the proximal
      tibiae, while a group without implantation was used as a control. Histological
      observation revealed that at two weeks after implantation, bone formation was
      initiated not only from the periosteum but in regions where the implants bordered
      on bone marrow. At four weeks, bone formation expanded from the marrow cavity
      side into the center of the implants, particularly in those implants with large
      pores. At twelve weeks, four implant groups showed repair of cortical defects and
      implant absorption, which was thought to be the result of natural bone remodeling
      mechanisms. The control group showed bone formation developed from the periosteum
      without bone induction in the marrow cavity, and at four weeks, the bone hole was
      almost healed. pQCT analysis revealed that the expansion rates of bone tissue
      were higher in the large-pore implant groups than in the small-pore groups. These
      data demonstrate the osteoconductivity of porous HAp/Col and the importance of
      its porous structure.

PMID- 19845155
TI  - Exogenous synovial stem cells adhere to defect of meniscus and differentiate into
      cartilage cells.
AB  - The meniscus is semilunar fibrocartilage, and its injury causes dysfunction of
      the knee. We previously reported a high chondrogenic potential of synovial
      mesenchymal stem cells (MSCs). Here, we examined whether intra-articular injected
      synovial MSCs adhered to the defect of the meniscus, survived there, and
      differentiated into cartilage cells. MSCs were isolated from the synovium of GFP
      rats. Cylindrical defects were created in the menisci in wild rats, and GFP
      positive synovial MSCs were injected into the knee. In the control group, 100
      microl of PBS was injected into the contralateral knee. The menisci were analyzed
      after day 1, weeks 2, 4, 8, and 12. One day after injecting of 10(7) GFP-positive
      synovial MSCs, the meniscal defect was filled with the cells. The GFP-positive
      synovial MSCs expressed type II collagen, exhibited representative
      characteristics of chondrocytes by electron microscopy at 8 weeks, and could
      still be observed at 12 weeks. The histological score improved within 12 weeks
      but there were no statistical difference between the two groups at each period in
      this model. GFP mRNA expressions were not observed in distant organs at day 1.
      After intra-articular injection, synovial MSCs attached to the meniscal defect
      and differentiated into cartilage cells.

PMID- 19845156
TI  - Gamma-delta T cell is essential for allergen-induced late asthmatic response in a
      murine model of asthma.
AB  - BACKGROUND: Gamma-delta (gamma-delta) T cells regulate immune responses at
      mucosal surfaces. Whether they can modify allergen-induced early (EAR) and late
      airway responses (LAR) is unknown. OBJECTIVE: We have tested the hypothesis that
      the gamma-delta T cells enhance allergen-induced airway responses in mice.
      METHODS: BALB/c wild-type (WT) mice and gamma-delta T cell-deficient (gamma-delta
      T-cell KO) mice were sensitized by intraperitoneal injection of ovalbumin (OVA)
      on days 1 and 15, immunized with 1% OVA aerosol on days 29-31, and challenged
      with 5% OVA or saline on day 33. Enhanced pause (Penh) was measured and BAL fluid
      was collected after challenge. Serum IgE was measured before challenge. The
      percentage of interleukin (IL)-4 and interferon (IFN)-gamma producing T cells in
      splenocytes from sensitized animals was determined by flow cytometry. RESULTS:
      Both EAR and LAR were observed in OVA-challenged WT mice. LAR but not EAR was
      inhibited in OVA-challenged gamma-delta T-cell KO mice. Gamma-delta T-cell KO
      mice showed less eosinophilia in BALF and serum OVA-specific IgE. In the
      sensitization period, the percentage of IFN-gamma producing alpha-beta T cell in
      gamma-delta T-cell KO mice was higher than that in WT mice. CONCLUSION: gamma
      delta T cells enhance LAR and airway inflammation but not EAR in this model of
      asthma.

PMID- 19845157
TI  - Co-overexpression of GDNF and GFRalpha1 induces neural differentiation in neural
      progenitor cells in comparison to bone marrow stromal cells.
AB  - Neural progenitor cells (NPCs) and bone marrow stromal cells (BMSCs), both of
      which can differentiate into neural phenotypes, are important candidates for
      transplantation therapy in the central nervous system (CNS). In most cases of
      BMSC transplantation, functional recovery is recognized even if few transplanted
      cells survive in the host tissue. A reason for this may be that transplanted
      cells produce neurotrophic factors (NFs), which enhance neuronal survival and
      neurite outgrowth after CNS injury. To provide additional insight into cell
      therapy, we investigated the types of NFs and receptors that are expressed in
      NPCs and BMSCs in vitro. Both cells expressed the mRNA of nerve growth factor
      (NGF), cilliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic
      factor (GDNF), and their receptors in the proliferative state. Real-time PCR
      analysis showed that mRNA expression of GDNF was relatively low in NPCs although
      its receptor was highly expressed. We thus tested if the overexpression of GDNF
      in NPCs affected neural differentiation without FGF-2. The overexpression of GDNF
      did not affect mRNA expression of beta-III tubulin and neuron specific enolase
      (NSE), but both GDNF and GFRalpha1 overexpression increased the expression of
      neuronal markers. These results suggest that augmentation of both GDNF and
      GFRalpha1 could have positive effects during neural tissue repair.

PMID- 19845158
TI  - The influence of occlusal stimuli on basic fibroblast growth factor expression in
      the periodontal healing of replanted teeth.
AB  - Occlusal stimuli and the periodontal healing of replanted teeth have been
      reported to be related. However, the mechanism for preventing dentoalveolar
      ankylosis remains unclear. Basic fibroblast growth factor (bFGF/FGF-2) is
      considered as a key factor in wound healing. The purpose of this study was to
      evaluate the relationship between occlusal stimuli, bFGF, and the periodontal
      healing after tooth replantation. Five-week-old male rats were divided into non
      occluded, occluded, and recovery groups. The right maxillary first molars were
      replanted in all groups, and the left maxillary first molars in the 2-week
      occluded group without replantation were served as nontreated. An anterior bite
      plate was attached to the maxillary and mandibular incisors to produce occlusal
      hypofunction in the non-occluded group and was then removed after 1 week in the
      recovery group. Histological observations were performed after 1 and 2 weeks of
      the experimental period. After 2 weeks, the non-occluded group had detectable
      ankylosis and obvious periodontal tissue stricture. Meanwhile, the occluded and
      recovery groups showed enlarged and thickened periodontia without ankylosis. The
      number of bFGF-positive cells in the occluded and recovery groups significantly
      increased as compared to in the non-occluded group. These results suggest that
      occlusal stimuli enhance the production of bFGF in the periodontal healing of
      replanted teeth and prevent dentoalveolar ankylosis.

PMID- 19845159
TI  - Effects of cryopreservation on bone marrow derived mesenchymal cells of a
      nonhuman primate.
AB  - Bone marrow stromal cells (MSCs) have multi-lineage differentiation capabilities
      and are focused on as a cell source for various cell therapies. To facilitate the
      availability of MSCs, cryopreservation technique is one of the critical factors
      for the cell therapies. In this study, effects of cryopreservation on
      capabilities of MSCs derived from a nonhuman primate were tested, aimed at a
      clinical application for tissue-engineered bone reconstruction. Effects of
      cryopreservation on the MSCs' adhesion rate, proliferation, and osteogenic
      differentiation in vitro were compared with non-cryopreserved MSCs. Bone
      formation capabilities were also tested using an extraskeletal bone induction
      model. The bone formation inducted by the combination of cryopreserved MSCs and
      an artificial bone scaffold was confirmed in all cases. The amount of bone
      formation at each case was irregular, but the results were suggested the
      possibility of cryopreserved MSCs on clinical use.

PMID- 19845160
TI  - Analyses of copy number and mRNA expression level of the alpha-synuclein gene in
      multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a sporadic neurodegenerative disease manifested
      clinically by progressive ataxia, parkinsonism, and autonomic dysfunction. Its
      cause is unknown, and there is no curative therapy. Alpha-synuclein is an
      important protein forming aggregations called glial cytoplasmic inclusions (GCIs)
      in oligodendroglia; these aggregations are considered important in MSA
      pathogenesis. Overexpression of the human alpha-synuclein gene in mice induces
      the formation of GCI-like aggregations in oligodendrocytes, leading mice to
      exhibit neurological signs similar to those in MSA patients. However, previous
      studies have excluded mutations within the coding region of the alpha-synuclein
      gene in MSA patients. To determine whether alteration in the expression level of
      the alpha-synuclein gene is associated with MSA pathogenesis, we used TaqMan
      quantitative PCR assay to analyze the alpha-synuclein gene copy number in
      patients' genomes. We also used quantitative RT-PCR and in situ hybridization to
      analyze alpha-synuclein mRNA expression in MSA patients' brain tissues. We found
      no alteration in the alpha-synuclein gene copy number in the patients' genomes (n
      = 50). Quantitative analysis for alpha-synuclein mRNA by the TaqMan method showed
      that alpha-synuclein mRNA levels were comparable between control (n = 3) and MSA
      (n = 3) cerebella. On in situ hybridization, the number of neurons with alpha
      synuclein mRNA expression was no greater in the cerebella of MSA patients (n = 3)
      than in the controls (n = 3). However, GCIs were seen in these MSA specimens on
      immunohistochemistry for alpha-synuclein. These results suggest that alpha
      synuclein gene expression is not the fundamental cause of MSA.

PMID- 19845161
TI  - Properties of human dentin surface after ArF excimer laser irradiation.
AB  - Recently, improvement of the properties of dentin surface using dental lasers to
      increase bonding strength has been anticipated in the field of adhesive
      dentistry. The objective of this study was to investigate changes in the surface
      properties of human dentin after ArF excimer laser irradiation at different
      irradiation times, pulse repetition rates and energy densities. The SEM images of
      the irradiated surfaces were observed, and the contact angle and the roughness of
      the irradiated surface were measured. As a result, SEM demonstrated that the
      dentin surface became irregular following ArF excimer laser irradiation. When the
      energy density increased, the irregularity became more minute and dentinal
      tubules were more easily identified. By contrast, such changes were not observed
      when the irradiation time and pulse repetition rate were changed. Moreover, as
      energy densities increased, the contact angle tended to decrease and the surface
      roughness tended to increase. These results suggested that the area of the
      irradiated surface and wettability increased after irradiation with the ArF
      excimer laser. Consequently, irradiation with ArF excimer lasers could improve
      the surface properties and be potentially useful for adhesive dentistry.

PMID- 19845162
TI  - Fibrous change of the infrapatellar fat pad due to strenuous running exercise and
      its treatment with intraarticular hyaluronan injection in a rat model.
AB  - The objective of the study was to determine whether strenuous running exercise
      produces a significant amount of fibrosis in the infrapatellar fat pad (IFP) of
      the knee and whether intraarticular injections of hyaluronan (HA) protect
      fibrosis in the IFP in a rat running model. Strenuous running exercise was
      performed on a rodent treadmill with 5% inclination using Wistar rats. After the
      exercise, hyaluronan was injected into the right knee joint once per week in the
      HA injection group. In the treatment control group of the left knee, no injection
      was done. Also, the running exercise group and the sedentary control group
      received no HA injection. The IFP was analyzed histologically and
      immunohistochemically after 1 week (5 km), 2 weeks (10 km), 3 weeks (15 km) and 6
      weeks (30 km). The inflammatory reaction in the IFP was not prominent at each
      running stage. A slightly, but significantly increased amount of inflammatory
      cell infiltration appeared during strenuous running. The amount of collagen
      fibers increased significantly at 30 km stage. Histological scores showed less
      fibrosis of the IFP in the HA injection group than in the control group at 30 km
      run. Strenuous running exercise may cause fibrosis in the IFP of runners.
      Intraarticular HA injection will inhibit arthrofibrosis of painful runners.

PMID- 19845163
TI  - Tensile strength of dentin after bleaching treatment.
AB  - The mechanical properties of dentin are changed after bleaching, although the
      effects of the bleaching conditions on the tensile strength of dentin have not
      been determined. In the current study, a tensile test of bovine dentin was
      conducted after bleaching and the effects of the bleaching conditions were
      investigated, including the number of bleaching times, the location where the
      bleaching agent was applied, and the kind of illumination. The weight of organic
      content in dentin before and after application of the agent was also measured.
      The results showed that the tensile strengths did not change after three times
      office bleaching procedure, and the location where the bleaching agent was
      applied, the kind of bleaching agent and the kind of illumination did not have
      influence on the tensile strength. On the other hand, organic component in dentin
      significantly decreased after application of the agent (p<0.05). Since the
      bleaching agent would potentially affect tensile strength with deterioration of
      collagen matrix, the frequency of bleaching treatment should be minimized in
      clinical use.

PMID- 19845164
TI  - UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in nuclei and
      rimmed vacuoles of muscle fibers in DMRV (distal myopathy with rimmed vacuoles).
AB  - BACKGROUND: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE)
      is a key molecule in the pathogenesis of distal myopathy with rimmed vacuoles
      (DMRV) and hereditary inclusion body myopathy (HIBM) and almost all such patients
      have some mutations in GNE. However, subcellular localization of GNE and the
      mechanism of muscular damage have not been clarified. METHODS: A rabbit
      polyclonal antibody for GNE was prepared. Immunohistochemistry was performed
      using anti-GNE and anti-nuclear protein antibodies. Western blotting with
      subcellular fractionated proteins was performed to determine subcellular
      localization of GNE. The sizes of myonuclei were quantified in muscle biopsies
      from patients with DMRV and amyotrophic lateral sclerosis (ALS). RESULTS: In DMRV
      muscles, immunohistochemistry identified GNE in sarcoplasm and specifically in
      myonuclei and rimmed vacuoles (RV). Nuclear proteins were also found in RVs.
      Immunohistochemistry showed colocalization of GNE and emerin in C2C12 cells.
      Western blotting revealed the presence of GNE in nuclear fractions of human
      embryonic kidney (HEK) 293T cells. The mean size of myonuclei of DMRV was
      significantly larger than that of ALS. CONCLUSION: GNE is present in myonuclei
      near nuclear membrane. Our results suggest that myonuclei are involved in RV
      formation in DMRV, and that mutant GNE in myonuclei seems to play some role in
      this process.

PMID- 19845165
TI  - Natural orifice translumenal endoscopic surgery: current status.

PMID- 19845166
TI  - The accuracy and role of cross-sectional imaging in the diagnosis of acute
      appendicitis.
AB  - Based on current literature review, most patients with suspected or possible
      appendicitis should undergo cross-sectional imaging. CT scanning is preferred in
      most patients; US is recommended in children or pregnant women. MRI is usually
      indicated in women or children with nondiagnostic US. Thin young men with classic
      history, laboratory studies, and examination are best managed with standard
      appendectomy without imaging. Most other patients should undergo cross-sectional
      imaging (i.e., CT scan).

PMID- 19845167
TI  - Management of pancreatic serous cystadenomas.
AB  - With more widespread use of imaging, cystic neoplasms of the pancreas are being
      diagnosed with increased frequency. Serous cystadenomas are the most common type
      of cystic neoplasm of the pancreas and have a natural history and malignant
      potential different than that of other cystic neoplasms. Although characteristic
      findings on imaging may be supportive, definitive diagnosis of these lesions
      often cannot be made by imaging alone. Endoscopic ultrasound with fine needle
      aspiration and cyst aspiration may facilitate the diagnosis, and after definitive
      diagnosis, patients with lesions that are small and asymptomatic may be followed
      with serial imaging. If definitive diagnosis cannot be made or if the patient is
      symptomatic, resection is warranted. In addition, large (> 4 cm) serous
      cystadenomas should be resected in appropriate surgical candidates given their
      propensity for growth and developing symptoms.

PMID- 19845168
TI  - Stem cells and the liver: clinical applications in transplantation.
AB  - ESLD affects millions of Americans, and HCV is a worldwide pandemic.
      Unfortunately, the ability to study liver disease and novel therapeutics
      experimentally in the laboratory is limited by an ongoing lack of small animal
      models. The development of rodents with livers chimeric for human hepatocytes may
      improve this situation. The authors' efforts currently use an immunodeficient or
      exogenously immunosuppressed animal with subsequent liver injury provided by
      chemical or surgical means. Cell transplantation with either human hepatocytes or
      human stem cells results in engraftment and subsequent "humanization" of an
      animal liver. Study of these animal models may lead to innovative approaches to
      the management of ESLD in both children and adults.

PMID- 19845169
TI  - Is intermittent vasculogenic claudication still a nonsurgical disease?

PMID- 19845170
TI  - Changes in operative case experience for general surgery residents: has the 80
      hour work week decreased residents' operative experience?

PMID- 19845171
TI  - Laparoscopic pancreatic resections.
AB  - The last decade has seen an increase in the application of minimally invasive
      surgical procedures to the management of pancreatic disease. Laparoscopic
      pancreatic surgery is an advanced laparoscopic procedure with a significant
      learning curve. It should be considered only by surgeons with extensive
      experience in open pancreatic surgery who possess advanced laparoscopic 'skills.
      Early reports suggest that laparoscopic pancreatic surgery can be accomplished
      with acceptable morbidity and mortality for the resection of small benign and low
      grade malignant lesions in the body and tail of the pancreas and for the internal
      drainage of pancreatic pseudocysts. Its role in the management of lesions in the
      head, neck, and uncinate process of the pancreas is yet to be determined.

PMID- 19845172
TI  - The role of perioperative hyperglycemia in postoperative infections.
AB  - In the past decade, convincing evidence has emerged that perioperative glycemic
      control in certain settings, especially cardiac surgery and the surgical ICU, can
      decrease morbidity and mortality. It remains unclear, however, if hypoglycemia is
      a cause of death or marker of patient acuity. It is clear, however, that the
      particular intensive glycemic control protocol matters because the rate of
      hypoglycemia varies across protocols and institutions. The best current evidence
      for tight control rests in the population of surgical patients needing more than
      5 days of critical care. Many questions still remain, such as the optimum blood
      sugar or the best protocol to implement glucose control, minimizing hypoglycemia.
      Further information will become available from the Normogylcemia in Intensive
      Care Evaluation and Survival Using Glucose Algorithm Regulation trial, currently
      enrolling patients in a prospective randomized trial to answer some of these
      outstanding questions. Maintaining euglycemia postoperatively is a simple and
      actionable step that could decrease the risk of postoperative infections and
      postoperative mortality.

PMID- 19845173
TI  - Can ileal pouch anal anastomosis be used in Crohn's disease?
AB  - Restorative proctocolectomy with IPAA is now accepted as the standard of care in
      most patients with a diagnosis of mucosal ulcerative or IndC requiring surgery.
      In patients with Crohn's colitis needing intervention, proctocolectomy with end
      ileostomy or subtotal colectomy with ileorectal anastomosis is still the
      treatment of choice. In the authors' institution they consider performing an
      ileal pouch for a diagnosis of Crohn's colitis requiring rectal resection
      provided there is no existing or previous evidence of perianal or small bowel CD.
      They only perform this in a well-motivated patient who understands the potential
      sequelae, including an increased incidence of adverse effects and reduced
      functional outcome, if they develop CD of the pouch. A significant amount of time
      must be allocated to the patient and their family when counseling them with
      regards to the potential surgical options and outcomes associated with each. The
      development of CD of the pouch is associated with a considerable pouch failure
      rate requiring pouch excision or indefinite ileostomy formation. It does not
      always herald disaster, however, and a large percentage of patients can be
      salvaged using a combination of medical and surgical therapy. In this patient
      group the maintenance of intestinal continuity and avoidance of an ostomy is
      often the most important factor in their perception toward quality of life. The
      search for a serologic or genetic marker that will predict disease outcome in
      this select patient group and thereby direct surgical decision making should
      continue. It is recommended that in the presence of Crohn's colitis the decision
      to perform an ileal pouch should only be made in a tertiary center under the care
      of gastroenterologists, histopathologists, and colorectal surgeons with
      experience in the management of these complex cases.

PMID- 19845174
TI  - Are airbags effective in decreasing trauma in auto accidents?
AB  - Multiple studies have addressed the effect of airbags on injury and mortality
      after motor vehicle collision with discrepant results (Table 1). Although large,
      population-based studies have minimized the protective effect of airbags, the
      most recent studies examining airbags have shown a decrease in injury and death,
      with the greatest protective effect seen when they are used in conjunction with
      seatbelts. Optimal restraint use is also associated with a decrease in infectious
      morbidity and hospital resource utilization. The widespread use of seatbelts and
      airbags will continue to save lives and decrease morbidity after motor vehicle
      collision.

PMID- 19845175
TI  - Posterior retroperitoneoscopic adrenalectomy.
AB  - PRA has become our preferred technique for resection of relatively small, benign
      adrenal masses and isolated metastases to the adrenal glands. PRA offers a
      direct, minimally invasive approach to the adrenal glands and avoids the need to
      enter the peritoneal cavity, deal with intraabdominal adhesions, and mobilize
      adjacent organs-steps necessary during anterior laparoscopic adrenalectomy. In
      addition, some patients tolerate retroperitoneal CO2 insufflation better than
      intraperitoneal CO2 insufflation from a hemodynamic and respiratory perspective.
      Finally, bilateral PRA can be performed without the need for patient
      repositioning. PRA requires the surgeon to become comfortable with the anatomy of
      the adrenal gland and surrounding structures from the posterior perspective. In
      addition, the surgeon must become adept at working in the retroperitoneal space,
      which is relatively restricted compared with the large cavity created by
      insufflation of the intraperitoneal space. However, in our experience, the
      learning curve can be overcome in a relatively short period, and the posterior
      approach is particularly advantageous in patients who have undergone prior open
      abdominal surgery or who are moderately obese. Proper patient positioning and
      trocar placement, high-pressure CO2 insufflation, and mobilization of the
      inferior aspect of the adrenal gland from the superior pole of the kidney before
      dividing its other attachments are critical technical details that greatly
      facilitate the procedure. In experienced hands, PRA is safe and is an ideal
      option for patients who are candidates for minimally invasive adrenalectomy.

PMID- 19845176
TI  - Laparoscopic liver surgery.
AB  - Great advances have occurred in the field of laparoscopic hepatic surgery. It is
      now clear that in experienced hands, the laparoscopic method of liver resection
      is as safe as an open procedure. The key phrase in this last sentence is "in
      experienced hands". The new devices that are available might make an
      inexperienced hepatic surgeon, well-trained in laparoscopic surgery, embark on
      hepatic resection without thorough knowledge of hepatic anatomy. The converse may
      also be true. As no criteria for credentialing of laparoscopic hepatic surgeons
      exist, the decision as to who is sufficiently trained to perform these procedures
      is left to individual hospital credentialing boards. While a certification
      procedure defined by leaders in this field and supported by surgical societies
      would be welcomed, the ability to achieve and enforce these guidelines appear to
      be more of a challenge. In addition, while most comparison studies in this area
      conclude by suggesting that a randomized, clinical trial would be needed to
      definitively arrive at an answer regarding the benefits of minimally invasive
      liver surgery compared with open surgery, it would likely be extremely difficult
      to accrue patients, given the data presented in articles regarding the success of
      laparoscopic hepatic resections. The authors conclude that an
      internationalregistry of all laparoscopic cases should b e established to insure
      patient safety and a mechanism for self-monitoring.

PMID- 19845177
TI  - Primary sclerosing cholangitis: the role of extrahepatic biliary resection.
AB  - PSC is an idiopathic chronic cholestatic disease of the liver that has a variable
      clinical course. Patients should be managed based on the degree of liver
      dysfunction, as well as the degree of biliary obstruction and symptoms.
      Endoscopic biliary dilations provides symptomatic and biochemical relief with
      minimal morbidity and mortality. Endoscopic procedures, however, result in
      shorter overall and transplant-free survival than resection and may not decrease
      the incidence of cholangiocarcinoma. Dominant strictures that fail endoscopic
      management may harbor an underlying cholangiocarcinoma and surgical therapy
      should not be delayed. While transplantation is the option of choice in PSC
      patients with cirrhosis, extrahepatic biliary resection including the bifureation
      is a good therapeutic option in noncirrhotic patients. Resection of the
      extrahepatic biliary tree with the hepatic duct bifurcation should be considered
      in patients with a dominant extrahepatic stricture and preserved liver function.
      In the appropriately selected patient, extrahepatic biliary resection affords
      patients with survival rates equivalent to that of transplantation. In fact,
      extrahepatic biliary resection can potentially significantly delay or avoid
      transplantation. Extrahepatic biliary resection is a good durable option for
      noncirrhotic patients with PSC and a dominant extrahepatic stricture.

PMID- 19845178
TI  - Preoperative versus postoperative adjuvant therapy for adenocarcinoma of the
      pancreas.
AB  - Because there have been no RCTs of preoperative and postoperative AT sequencing
      in the treatment of resectable and borderline resectable pancreatic cancer, it is
      impossible to assess their relative values with confidence. Three nonrandomized
      experiences of both treatment approaches from single institutions provide some
      assurance that preoperative AT is not inferior to postoperative AT. Phase II
      trials for both resectable and borderline resectable tumors suggest that longer
      median survival can be obtained by a policy of preoperative AT. We will watch the
      European RCT with great interest.

PMID- 19845180
TI  - Can unresectable colorectal cancer be cured?
AB  - A multimodality regimen that includes EBRT, chemotherapy, maximal surgical
      resection, and IORT, when used in patients with initially unresectable primary
      colon or rectal adenocarcinoma, is associated with excellent long-term local
      control, and a 5-year overall survival of 52%. Distant metastases account for
      most treatment failures, occurring in roughly 50%. Treatment-related morbidity is
      high, with a long-term complication rate that approaches 50%. These results
      suggest that selected patients with advanced unresectable disease benefit from an
      aggressive approach. Additional effort needs to focus on reducing the rate of
      systemic failure with more effective chemotherapy regimens and minimizing the
      frequency of long-term procedural complications.

PMID- 19845179
TI  - Reviews of liability claims against surgeons: what have they revealed?
AB  - Closed claims reviews are a robust source of severe surgical errors for study.
      Most errors are preventable. Most preventable technical errors and judgment
      errors occur during care provided by competent surgeons. Failure to operate
      within a proper scope-of-practice is the most common cause of incompetence.
      Patient factors and systems failures, including human factors, cause or
      profoundly contribute to the cause of most technical errors. Regardless of its
      cause or preventability, a technical error sets the stage for other errors in
      care that relate to systems' failures and surgeons' judgment failures. Failed
      judgment and poor decision-making are usually the result of cognitive errors
      caused by flawed behavioral practices instead of lack of knowledge. Systems of
      care and good behavioral practices are catalysts that maximize the power of
      knowledge and skill to achieve good outcomes. The uniform application of
      knowledge and skill in a favorable environment is as important as the possession
      of knowledge and skill. Identifying systems and behavioral causes of errors may
      help to define best practices and lead to safer patient care through improved
      systems of care and increased diligent attention to ordinary tasks that require
      more time than knowledge on the part of surgeons.

PMID- 19845181
TI  - The current management of choledochal cysts.
AB  - Choledochal cyst disease is uncommon. The presentation of the disease is being
      seen more commonly in the adult population than in the pediatric population,
      particularly in the West, making this a diagnosis a general surgeon should
      consider when evaluating a patient with biliary disease. The diagnosis of this
      disease has been greatly facilitated by improving technologies, particularly MRCP
      and interventional techniques of PTC. The consequences of not treating
      choledochal cysts can result in malignant transformation. When possible, complete
      surgical excision of the cyst is recommended and should be performed as early as
      possible to prevent complications and the progression of liver fibrosis. Long
      term follow-up is required for surveillance for late complications and for
      cancer, particularly in type IV and V choledochal cysts where complete excision
      is not possible.

PMID- 19845183
TI  - Impact of the false-negative sentinel lymph node biopsy in melanoma.

PMID- 19845182
TI  - What is the effect of age on pancreatic resection?
AB  - Both morbidity and mortality rates following pancreatic resection increase with
      advanced age. The reported mortality rates following pancreatic surgery arc
      underestimated in single-institution studies. There is a significant publication
      bias where only centers with good results report their outcomes. The population
      based data are critical to provide a more realistic view of mortality rates
      following pancreatic resection. It is essential in counseling elderly patients
      that they understand that mortality rates are increased, morbidity rates are
      increased, and the effect of complications often leads to a prolonged
      convalescence. They will have a longer length of stay and up to a 30% to 40%
      chance that they will not be able to go home but will need to recover in an
      extended care facility following hospital discharge. Although the morbidity and
      mortality rates are increased for elderly patients, they are well within the
      acceptable range for major abdominal surgery when performed at experienced
      centers. Patients also need to be aware that surgical resection is the only
      curative option for pancreatic cancer. In reasonable risk elderly patients the
      benefit of surgical resection does not decrease with age and these patients can
      experience long-term survival and good quality of life. Once patients over 80 get
      beyond the 2-year survival mark without cancer recurrence their survival
      parallels that of their age-matched counterparts. One should also keep in mind
      that the reported survival rates are mostly for pancreatic cancer, but patients
      with other periampullary cancers have improved long-term survival when compared
      with those with pancreatic cancer. Elderly patients also need to be aware of the
      fact that hospital volume and surgeon experience significantly impact outcomes.
      The mortality rates following surgery in the oldest patients, those over 80, are
      nearly twice as high at low-volume facilities compared with high-volume
      facilities. The overall mortality rate and the difference decrease with
      decreasing age. This likely represents improved processes of care at experienced
      centers and better ability to manage the complications of pancreatic surgery,
      which occur more commonly in elderly patients. It is important to educate both
      physicians and elderly patients about this difference. Currently, elderly
      patients are less likely to be resected at high-volume centers than younger
      patients. The reasons for this are unclear but include lack of awareness of the
      importance of hospital volume and surgeon experience and reluctance of patients
      in this age group to travel long distances from home for their care. When
      reviewing the data, one must be aware that these studies (both population-based
      and single-institution) are retrospective and subject to significant selection
      bias. The elderly patients undergoing resection were dearly carefully chosen.
      There is still nihilism, however, toward aggressive care in these patients, with
      fewer than 10% of patients over 80 with locoregional disease and no comorbidities
      being resected, whereas 40% of patients 66 to 70 in the same category are
      resected. These data provide an excellent foundation to guide informed decision
      making in the elderly population with pancreatic and periampullary cancer.
      Patients need to know that surgical resection offers the only hope for cure and
      that the benefit of surgical resection does not diminish with age. The diagnosis
      (pancreatic versus other periampullary cancers versus benign disease or
      premalignant lesions) needs to be taken into account to balance fully the risks
      and benefits. Older patients need to be aware of the increased morbidity,
      mortality, and prolonged convalescence they may experience. They also need to be
      advised to have their surgery done by experienced surgeons at experienced centers
      where these complications can be best managed. Further studies are needed to
      guide patient selection. The effect of patient comorbidities, cognitive status,
      preoperative functional status, and frailty need to be more formally assessed to
      select patients, maximize surgical resection in appropriate candidates, and
      improve short-term outcomes. Once better characterized, specialized geriatric
      pathways may optimize surgical resection rates, streamline care, and improve
      outcomes in this challenging population. Age alone, however, should not be a
      contraindication to pancreatic resection in elderly patients with pancreatic
      cancer.

PMID- 19845184
TI  - Adjuncts to liver surgery: is acute normovolemic hemodilution useful for major
      hepatic resections?
AB  - For patients undergoing major hepatic resection, acute normovolemic hemodilution
      is a safe technique that effectively reduces allogeneic red blood cell
      transfusions. In the recent prospective randomized controlled trial completed at
      MSKCC, there was no difference in the extent of resection, intraoperative blood
      loss, operative time, incidence and grade of complications, or length of hospital
      stay between patients who underwent ANH versus standardintraoperative management.
      Although ANH does reduce the rate o f allogeneic red blood cell transfusions in
      patients undergoing major hepatectomy, its benefit is particularly pronounced in
      patients who have significant operative blood loss (i.e., >800 mL). In these
      patients, the benefit of ANH extends also to the transfusion of FFP. Thus, ANH
      should be considered for routine use in patients undergoing major hepatectomy who
      have an expected considerable blood loss. However, given the relatively low
      transfusion rate overall, future efforts should be directed at preoperatively
      identifying patients most likely to benefit from ANH.

PMID- 19845185
TI  - Solid pseudopapillary neoplasms of the pancreas.
AB  - SPN is a rare neoplasm that affects mainly young women. Despite this feature, SPN
      have been seen in both genders, multiple races, and at a wide range of ages. The
      genetic mechanism behind the development of SPN is distinct from the more lethal
      ductal carcinoma of the pancreas. This difference is reflected in the favorable
      outcome for patients with SPN. Surgery is typically curative in patents with
      localized disease and possibly in patients with limited metastasis or local
      extension. No consensus exists on an effective systemic therapy. There are no
      reliable predictors for disease-specific mortality or recurrence in the minority
      of patients who develop aggressive disease.

PMID- 19845186
TI  - Should all distal pancreatectomies be performed laparoscopically?
AB  - Despite the relatively slow start of laparoscopic pancreatectomy relative to
      other laparoscopic resections, an increasing number of these procedures are being
      performed around the world. Operations that were once considered impossible to
      perform laparoscopically, such as pancreaticoduodenectomy and central
      pancreatectomy are gaining momentum. Technology continues to improve, as does
      surgical experience and prowess. There are both enough experience and data
      (though retrospective) to confirm that LDP with or without spleen preservation
      appears to be a safe treatment for benign or noninvasive lesions of the pancreas.
      Based on the fact that LDP can be performed with similar or shorter operative
      times, blood loss, complication rates, and length of hospital stay than ODP, it
      can be recommended as the treatment of choice for benign and noninvasive lesions
      in experienced hands when clinically indicated. It is very difficult to make
      clear recommendations with regard to laparoscopic resection of malignant
      pancreatic tumors due to the lack of conclusive data. As long as margins are
      negative and lymph node clearance is within accepted standards, LDP appears to
      have no untoward oncologic effects on outcome. Certainly more data, preferably in
      the manner of a randomized clinical trial, are needed before additional
      recommendations can be made. Potential benefits of laparoscopic resection for
      cancer include the ability to inspect the abdomen and abort the procedure with
      minimal damage if occult metastases are identified. This does not delay the onset
      of palliative chemotherapy, which would be the primary treatment in that
      circumstance. In fact, there is evidence to suggest that there is a greater
      likelihood of receiving systemic therapy if a laparotomy is avoided in patients
      who have radiologically occult metastases. Patients may also undergo palliative
      laparoscopic gastric and biliary bypass if indicated. Faster wound healing may
      also translate into a shorter waiting time before initiating adjuvant
      chemotherapy and/or radiation therapy. If the patient develops a wound infection,
      the infection should be more readily manageable with smaller incisions. Although
      not proven clinically relevant in humans, the reduction in perioperative stress
      associated with laparoscopic resection may translate to a cancer benefit for some
      patients. One report compared markers of systemic inflammatory response in 15
      subjects undergoing left pancreatectomy. Eight had hand-access laparoscopic
      procedures and the rest had standard open surgery. The subjects in the
      laparoscopic group had statistically lower C-reactive protein levels than the
      open group on postoperative days one (5.5 mg/dL versus 9.7 mg/dL, P = .006) and
      three (8.5 mg/dL versus 17.7 mg/dL, P = .003), suggesting that the laparoscopic
      approach to left pancreatectomy is associated with less inflammation. While this
      report is underpowered, it supports the notion that MIS cancer surgery may induce
      less of a systemic insult to the body than standard open cancer surgery. More
      work in this area is necessary before any firm conclusions can be drawn. An
      important issue to consider is that of training surgeons to perform these complex
      procedures laparoscopically. Not all pancreatectomies are amenable to the
      laparoscopic approach, even in the most skilled hands. As such, only a percentage
      of cases will be performed this way and expectations to educate surgeons
      adequately to perform advanced laparoscopic procedures can be unrealistic,
      resulting in more "on-the-job" training. Another aspect that draws some
      controversy is that of the totally laparoscopic procedure versus the hand-access
      approach. No laparoscopic instrument provides the tactile feedback possible to
      obtain with the hand. The HALS approach allows for this, and the opportunity to
      control bleeding during the procedure. HALS also provides a way to improve
      confidence during the learning-curve phase of these operations. Finally, it is
      important to remember that if the procedure is failing to progress
      laparoscopically, or if cancer surgery principles are likely to be violated, the
      surgeon (and the patient) must be willing to abort the laparoscopic approach and
      complete the operation using standard open technique. During the next few years
      we can expect to see more robust outcome data with laparoscopic pancreatectomy.
      The expectation is that more data will come to light demonstrating benefits of
      laparoscopic pancreatic resection as compared with open technique for selected
      patients. Several groups are considering randomized trials to look at these
      endpoints. Although more retrospective and prospectively maintained data will
      certainly be presented, it is less likely that randomized data specifically
      examining the question oflaparoscopic versus open pancreatectomy for cancer will
      mature, due to some of the limitations discussed above. Additional areas of
      discovery are in staple line reinforcement for left pancreatectomy and suturing
      technology for pancreatico-intestinal anastomosis. Robotic surgery may have a
      role in pancreatic surgery. Improving optics and visualization with flexible
      endoscopes with provide novel surgical views potentially improving the safety of
      laparoscopy. Another area in laparoscopic surgery that is gaining momentum is
      that of Natural Orifice Transluminal Endoscopic Surgery (NOTES). NOTES represents
      the "holy grail" of incisionless surgery. Can we enucleate a small tumor off the
      pancreatic body by passing an endoscope through the gastric (or colonic) wall,
      and bring the specimen out via the mouth or anus? Can we use this approach for
      formal left pancreatectomies? Pioneers have already developed a porcine model of
      left pancreatectomy. This technology must clear several hurdles before it is
      cancer ready; however, technology is moving at a rapid pace.

PMID- 19845187
TI  - Management of composite defects of the nose, cheek, eyelids and upper lip.
AB  - AIM: To assess the results of reconstruction of composite defects involving the
      nose which extend to involve the cheeks, eyelids or upper lip. STUDY DESIGN:
      Retrospective observational study. MATERIAL: Sixteen patients with defects of the
      nose extending to the adjoining cheek, upper lip or eyelid. METHOD: A combination
      of flaps and grafts were needed to reconstruct these defects so that the
      aesthetic subunits were replaced and joined at their junctions wherever possible.
      RESULTS: Where the defect required three or four flaps, there was some
      unpredictable cicatrisation at their junction that resulted in some asymmetry.
      This problem primarily occurred at the alar base, and was compounded if there was
      tissue loss of the premaxilla or maxilla. CONCLUSION: If a defect that involves
      the nose, cheek and upper lip is repaired with a combination of cheek
      advancement, nasolabial, paramedian forehead and/or septal flaps, there can be
      unpredictable cicatrisation at their junction, particularly at the alar base. In
      these circumstances, we recommend replacing the nasal and other defects with a
      slightly more generous amount of tissue than would be taken to repair a similar,
      but solitary, defect. It is important to replace any loss of the facial skeleton,
      in order to provide support for overlying flaps.

PMID- 19845188
TI  - Microlaryngoscopic and office-based injection of bevacizumab (Avastin) to enhance
      532-nm pulsed KTP laser treatment of glottal papillomatosis.
AB  - OBJECTIVES: Photoangiolytic lasers effectively treat glottal papillomatosis, but
      do not reliably prevent recurrence. Therefore, sublesional injections of the
      antiangiogenic agent bevacizumab (Avastin) were given to assess the effect on
      disease recurrence and phonatory function. METHODS: A retrospective investigation
      was done in a pilot group of 10 adult patients with bilateral glottal
      papillomatosis who had prior angiolytic laser treatment with established patterns
      of recurrence. The patients underwent 5 bevacizumab injections (5 to 10 mg) into
      the diseased vocal folds along with 532-nm pulsed KTP laser photoangiolysis
      treatments 4 to 6 weeks apart. Their disease resolution was compared to findings
      from prior laser treatment alone, and objective measures of vocal function
      (acoustic, aerodynamic, Voice-Related Quality of Life survey) were obtained.
      RESULTS: All 10 patients had a greater than 90% reduction in recurrence. Four of
      the 10 had resolution. Four of the 10 have limited recurrent or persistent
      disease, receive injections of bevacizumab at 8- to 12-week intervals, and have
      not required laser treatment. Two of the 10 have ongoing periodic office-based
      KTP laser treatment along with bevacizumab injections. No patient has required
      microlaryngeal surgery with general anesthesia, and all 10 have had substantial
      improvement in vocal function. CONCLUSIONS: This pilot investigation provides
      preliminary evidence that bevacizumab injections enhance photoangiolytic laser
      treatment of glottal papillomatosis while enhancing phonatory function. Coupling
      an antiangiogenesis agent with pulsed KTP laser photoangiolysis is conceptually
      promising, since the mechanisms of action are complementary.

PMID- 19845189
TI  - On the treatment and recurrence of papilloma of the larynx [1882].

PMID- 19845190
TI  - Beyond the state of the art in ethics consultation.

PMID- 19845191
TI  - Physician orders to supplement advance directives: rescuing patient autonomy.
AB  - To adapt Churchill's comment on democracy, "No one pretends that [POLSTs are]
      perfect..." but physicians' orders about life-sustaining treatments are a very
      important supplement to advance directives, especially for patients who are
      extremely or terminally ill, and most particularly for patients who require
      emergency treatment by first responders or by physicians who do not know them as
      persons. The standardized orders of limited options, however, are no substitute
      for a detailed treatment directive of a patient with a known illness, with
      predictable trajectories and complications. And, in this latter circumstance, a
      thoroughly informed proxy may also assist physicians in selecting appropriate
      treatment for patients who have lost decisional capacity and/or the ability to
      express it. I believe all patients should have an advance directive, preferably a
      combined proxy-treatment directive, and preferably one that has been thoroughly
      discussed with the attending physician and with the proxy, successor proxies, and
      preferably relatives and friends. Nurses, social workers, and chaplains may be
      very helpful to the patient in thinking through his or her preferences,
      especially if the severity of illness and the limited efficacy of interventions
      are such that the patient would wish to omit life-sustaining treatment or to
      discontinue it after a time-limited trial. Finally, because POLST is new or yet
      to be initiated in many areas of the country, it behooves all physicians to
      become knowledgeable of POLST and to initiate discussion of it with colleagues,
      patients, patients' proxies, and with relatives of patients. Even more recent is
      the combined advance directive/physician's orders to permit natural dying,
      actionable immediately for patients suffering severely and irremediably, but
      actionable at a future time if the patient progresses to advanced stages of
      dementia or other devastating brain disorders. In order to encourage physicians
      to initiate advance care planning with their patients, this quote from a patient
      shortly before his death from prostatic cancer might prove helpful: "Not every
      patient can be saved, but his illness can be eased by the way that the doctor
      responds to him. In learning to talk to his patients, the doctor may talk himself
      back into loving his work. He has little to lose and everything to gain by
      letting the sick man into his heart. If he does, they can share--as few others
      can--the wonder, terror, and exultation of being on the edge of being"

PMID- 19845192
TI  - Integrating ethics and patient safety: the role of clinical ethics consultants in
      quality improvement.

PMID- 19845193
TI  - When humor in the hospital is no laughing matter.

PMID- 19845194
TI  - Non-adherence to instructions to cancel a cycle in a patient overstimulated with
      gonadotropins in a planned intrauterine insemination cycle.

PMID- 19845195
TI  - Preventive ethics and subsequent care of patients self-administering ovarian
      stimulation for the management of infertility.

PMID- 19845196
TI  - Boldt v. Boldt.

PMID- 19845197
TI  - Where is the child? Circumcision and custody in Boldt v. Boldt.

PMID- 19845198
TI  - Boldt v. Boldt: A pediatric ethics perspective.
AB  - On balance, the potential harms and benefits of circumcision in an older child or
      adolescent are sufficiently closely aligned that parents should be permitted to
      make decisions about circumcision on behalf of their children. To make a case for
      prohibition, medical harms would have to be of such likelihood and magnitude that
      no reasonable potential benefit (social, religious, cultural, or medical) could
      justify doing it to a child. However, I would suggest that the following
      additional principles should apply: (1) Informed permission from parents is
      essential. Only about half of the parents considering neonatal circumcision are
      given any substantive information about the procedure. That practice is not
      acceptable for a procedure that is not medically essential and carries some risk
      of harm. A fully informed consent is essential, and must include a balanced
      discussion of potential harms and benefits of the procedure to the child. Parents
      should be given accurate and impartial information and allowed to make an
      informed decision regarding what is in the best interest of the child. (2)
      Consent of both parents should be required when the procedure is not medically
      required. It should not be performed in the face of parental disagreement. (3)
      Absent a significant medical indication, circumcision should not be performed on
      older children and adolescents in the face of dissent or less than enthusiastic
      assent. (4) Circumcision should be performed competently and safely by adequately
      trained providers.29 This should include infection-control measures, a sterile
      environment for the procedure, and no mouth-penis contact. (5) Analgesia is safe
      and effective. Adequate analgesia and post-operative pain control must be
      provided. In the case of Jimmy Boldt, I would suggest that without some
      compelling medical reason for performing a circumcision, the procedure should not
      be performed in the absence of agreement between his parents. The fact that
      Jimmy's father had sole custody does not eliminate the mother's ethical right and
      obligation to look after the welfare of her son. While the mother may not have
      legal decision-making authority, that legal determination does not appear to be
      related either to a lack of interest in her son's welfare or an inability to
      carry out that role. Jimmy is her son, and she has an interest in seeing his
      welfare protected. Whether or not she has legal rights, I would be very reluctant
      to perform an elective procedure for cultural or religious reasons without the
      permission of both parents and the unambiguous assent of Jimmy himself. Neither
      appears to be present in the case as it presented to the courts.

PMID- 19845199
TI  - Circumcision, conversion, and deciding for a minor: some Jewish perspectives.

PMID- 19845200
TI  - The diagnosis of dying.

PMID- 19845201
TI  - As prickly as a porcupine: reflections on a systems-based "experiential sculpting
      exercise".

PMID- 19845202
TI  - Surrogates have not been shown to make inaccurate substituted judgments.

PMID- 19845203
TI  - Legal briefing: medical futility and assisted suicide.

PMID- 19845204
TI  - UPDATE: summary of March changes from CMS hospital deeming application.

PMID- 19845205
TI  - UPDATE: revised scoring for all 2009 accreditation manuals.

PMID- 19845206
TI  - UPDATE: target analysis methodology for assessing hospital performance.

PMID- 19845207
TI  - UPDATE: comparing Joint Commission and CMS telemedicine requirements.

PMID- 19845208
TI  - APPROVED: an extension for extension surveys.

PMID- 19845209
TI  - ERRATA: all 2009 accreditation and certification manuals.

PMID- 19845210
TI  - Cognitive impairment and mortality--an issue worth remembering.
AB  - This edition of the Journal of Insurance Medicine contains its third article
      addressing the mortality implications of cognitive impairment. In 2007, Vecchione
      and Golus reported the mortality (over an average of 7 years) of a cohort of
      employer-sponsored, long-term care (LTC) insurance applicants comparing those who
      were declined for cognitive impairment with those approved. The results of their
      analysis demonstrated a significant difference in mortality between applicants
      with low Delayed Word Recall (DWR) scores (0-5) vs the group with DWR scores of 6
      10. One of the limitations of the Vecchione and Golus study was that its dataset
      consisted of a cohort of group LTC applicants potentially limiting its
      applicability to a population of individually underwritten life insurance
      applicants.

PMID- 19845211
TI  - Minding your p's and q's--and m's too.

PMID- 19845212
TI  - A simple method for computer-based survival curve measurement.
AB  - An easy-to-use method for generating tabular data from a survival curve is given.
      This technique measures a given survival curve in units of pixels, then converts
      the data to a table of cumulative survival (P) vs time utilizing software already
      present on most computer systems.

PMID- 19845213
TI  - Cognitive impairment and mortality in the Cardiovascular Health Study.
AB  - Cognitive impairment is associated with increased mortality, depending on the
      severity of impairment. We analyzed data from the Cardiovascular Health Study
      (CHS), using Cox proportional hazards regression models to quantify the effect of
      the impairment. After adjustment for age, sex, and medical risk factors, we found
      the resulting relative risks to range from 1.19 for mild impairment to 1.98 for
      severe.

PMID- 19845214
TI  - Relative survival in dilated cardiomyopathy: a stratification study of long-term
      outcome to evaluate life insurance cover.
AB  - OBJECTIVES: The aim of this study was to compare mortality of dilated
      cardiomyopathy (DCM) patients with the mortality in the background Italian
      population, taking into account demographic characteristics and clinical
      stratification of long-term outcome, ie, "reverse remodelling" within the first 2
      years of follow-up. BACKGROUND: DCM is a myocardial disease, characterized by
      left and/or right ventricular dilation and dysfunction and poor outcome. Evidence
      based treatment with ACE inhibitors, beta-blockers and, in the last decade,
      implantable cardioverter defibrillators have been demonstrated to improve
      significantly heart failure symptoms and prognosis. At present, DCM patients are
      unlikely to be accepted for life insurance. METHODS: A cohort of 577 DCM patients
      consecutively enrolled from 1988 to 2004 in the Heart Muscle Disease Registry of
      Trieste, Italy, was matched by sex, age and registry data entry with the
      mortality data of the Italian population. Relative survival has been estimated by
      means of Kaplan-Meier technique, and mortality ratios (MR) with corresponding 95%
      confidence intervals have been computed. RESULTS: DCM patients who showed a
      significant reverse remodelling within the first 2 years of treatment showed
      comparable survival with respect to the control population, and therefore could
      be taken into consideration for life insurance coverage, at least for a short or
      medium-term of years. CONCLUSIONS: The data illustrate that survival probability
      strongly depend on the individual treatment and evolution of the disease and
      could be easily measured within the first 2 years of follow-up. If this
      information is collected at the time of evaluation of an applicant for life
      cover, the insurance company could possibly improve its risk stratification.

PMID- 19845215
TI  - Use of carotid intima-media thickness in an insurance context.
AB  - Measurement of carotid intima-media thickness (CIMI) with B-mode ultrasound is a
      non invasive technique for identifying subclinical vascular disease and
      estimating risk of future cardiovascular disease (CVD), such as myocardial
      infarction (MI), stroke, and death from coronary heart disease (CHD). Although
      the optimal use of CIMT has not been determined, the prevailing opinion is that
      it improves clinical risk prediction beyond the benefits of using only the
      traditional cardiovascular risk factors. The reason is because CIMT can detect
      early subclinical disease, and thus it's both a risk factor and a marker of CVD
      risk. CIMT thus has the potential to increase the accuracy of risk
      classification. The problem from both a clinical and an insurance perspective is
      the absence of reliable data that relate CIMT measurements to CVD incidence
      rates.

PMID- 19845216
TI  - Statin induced myopathy.
AB  - Statin drugs are widely used to reduce the risk of initial and recurrent
      cardiovascular events. Overall, their safety and tolerability is well
      established. However, there can be toxic effects on skeletal muscle tissue, the
      so-called statin induced myopathy. Usually this involves only subjective symptoms
      of muscle aching and weakness with normal CK values, but rarely a more severe
      myositis can occur with marked elevations of the CK. Statins do have different
      pharmacologic properties, and often one statin can be substituted without
      complications for another statin that has caused a myopathy.

PMID- 19845217
TI  - How sweet it is: McArdle's disease case report and discussion.

PMID- 19845218
TI  - Flirtatious P waves dancing around the QRS complex.
AB  - Interpreting the rhythm of an ECG may occasionally be challenging. A systematic
      approach along with knowledge of arrhythmias will usually lead to a correct
      diagnosis. In this ECG case study, we are presented with a very abnormal ECG in
      which the rhythm is irregular and occasional P waves are missing.

PMID- 19845219
TI  - Myocardial bridging.
AB  - Myocardial bridging is a congenital anomaly of the left anterior descending
      coronary artery resulting in systolic compression by overlying myocardial tissue.

PMID- 19845220
TI  - Riding a photon.

PMID- 19845221
TI  - Current strategies for surgical management for conjunctival and corneal
      intraepithelial neoplasia.

PMID- 19845222
TI  - A clinical approach for evaluation of glaucoma patients.
AB  - Clinicians are confronted with a plethora of new machines, new software, and new
      applications of technology, all intended to help with glaucoma management. It is
      helpful to return to basic principles, to see how these advances fit into our
      assessment of the intraocular pressure, optic nerve, and visual fields.

PMID- 19845223
TI  - Limbal stem cell study in contact lens wearers.
AB  - The effect of soft contact lens on the limbal stem cells was assessed in 30
      contact lens wearers, 19 controls, and 17 cases known to cause limbal stem cell
      deficiency. Different results were seen as compared to controls in all the four
      quadrants, but more severe in cases known to cause limbal stem cell deficiency.

PMID- 19845224
TI  - Combined oral corticosteroid-methotrexate therapy in Eales' disease.
AB  - The efficacy of combined oral corticosteroid and low-dose oral methotrexate
      pulsed therapy in Eales' disease was evaluated prospectively, based on weighted
      visual morbidity scale for disease activity and visual acuity grading in 36
      consecutive cases. Oral corticosteroids in a weekly tapering dose for 4 weeks and
      12.5 mg methotrexate as a single oral dose, once per week for 12 weeks, were
      administered simultaneously. We concluded that this combined oral therapy is
      clinically effective with an acceptable safety profile.

PMID- 19845225
TI  - The conjunctival flora in vernal conjunctivitis patients.
AB  - We investigated conjunctival flora changes in vernal conjunctivitis (VC) (n = 30)
      patients compared to the normal eye (n = 30). Growth was observed in 86.6% of the
      vernal group, and 80% of the control group specimens. We believe that
      administering prophylactic treatment would be helpful in VC patients who are to
      have intraocular surgery to prevent postoperative endophthalmitis.

PMID- 19845226
TI  - Ability of different optical imaging devices to discriminate between healthy and
      glaucomatous eyes.
AB  - We compared the ability to discriminate between healthy and glaucomatous eyes of
      three optical imaging devices in 140 eyes from 140 subjects. No statistically
      significant differences were found among the AUCs of these parameters. However,
      AUCs were significantly higher in OCT and HRT parameters than most of GDx VCC
      ones. Thus, structural parameters assessed by the optical imaging devices are
      useful to discriminate glaucomatous damage, but showed no significant difference
      among the best parameters from HRT, OCT or GDx VCC.

PMID- 19845227
TI  - Angle closure glaucoma and lens subluxation secondary to eye rubbing in a patient
      with mycosis fungoides.
AB  - We report an unusual case of angle closure glaucoma in a patient with the skin
      lymphoma mycosis fungoides. Constant eye rubbing led to bilateral lens
      subluxation and uncontrolled intraocular pressure.

PMID- 19845228
TI  - A rare case of bilateral eyelid ulceration with mycosis fungoides.
AB  - Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is a
      low-grade lymphoma usually occurring after the age of 50 years. We present a case
      of a 60-year-old man with cutaneous manifestations of MF, who later developed
      bilateral eyelid ulceration. MF is a highly recalcitrant disease with a
      relentless course. Our patient highlights a delayed presentation in MF with
      bilateral upper lid ulcerative lesions, which responded well to systemic
      chemotherapy, commenced for a visceral indication.

PMID- 19845229
TI  - Silent sinus syndrome.
AB  - We present a case of silent sinus syndrome (SSS) who underwent unilateral
      surgical endoscopic maxillary meatotomy. Orbital floor reconstruction is delayed
      after follow up. Enophthalmos recovered 8 months after the surgery and radiologic
      findings improved. SSS is a clinical entity that should be kept in mind in the
      differential diagnosis of enophthalmos and can be treated successfully via
      endoscopic approach.

PMID- 19845230
TI  - Recurrent endogenous Candida.
AB  - We report a 61-year-old who developed candidemia following pancreatic tumor
      surgery, and presented with bilateral multifocal chorioretinitis and vitritis.
      Chorioretinal lesions regressed with fluconazole therapy. Pars plana vitrectomy
      was performed with resultant improved visual acuity, but vitritis recurred with
      the next chemotherapy session. With the cessation of chemotherapy, vitritis
      regressed without any systemic treatment.

PMID- 19845231
TI  - Bone mineral density in women using depot medroxyprogesterone acetate (DMPA) for
      at least 2 years compared to a control group: a cross sectional study.
AB  - OBJECTIVE: To compare the effect of long-term use of depot medroxyprogesterone
      acetate (DMPA) on bone mineral density (BMD) in Thai women compared to the
      control. MATERIAL AND METHOD: A cross sectional study was conducted on Thai women
      of reproductive age who used DMPA (50 subjects) for contraception for at least 2
      years and non-hormonal users (50 subjects). BMD was measured at the lumbar spine,
      femur and distal radius, and ulna. RESULTS: There was significantly lower BMD at
      the lumbar spines in the DMPA group but there was no significant difference in
      BMD between groups at the femur distal radius, and ulna. CONCLUSION: Long-term
      use of DMPA has a negative impact on lumbar spine BMD.

PMID- 19845232
TI  - Capillary blood glucose screening (Accu-Chek Advantage) for gestational diabetes.
AB  - OBJECTIVE: To determine optimal threshold of capillary blood glucose screening
      (Accu-Chek Advantage) for gestational diabetes. STUDY DESIGN: A cross-sectional
      analytical study. MATERIAL AND METHOD: Capillary and venous blood of pregnant
      women who attended the antenatal clinic at Trang Regional Hospital between August
      2007 and May 2008 were collected for glucose testing (by approach of American
      Diabetes Association's Fourth International Workshop-Conference on Gestational
      Diabetes) at one hour after taking 50 gm glucose. The glucose values of Accu
      Check Advantage were compared with the standard venous plasma glucose. The
      receiver operator characteristic (ROC) curve was created to determine the optimal
      threshold of the capillary blood test screening for gestational diabetes.
      RESULTS: A total of 816 pregnant women were enrolled in the present study. Their
      capillary blood glucose values and plasma glucose values were checked with the
      Accu-Chek Advantage and the central laboratory chemistry analyzer respectively.
      The good correlation between capillary blood glucose and plasma glucose values
      was found (correlation coefficient = 0.80, 95% CI 0.77-0.82). There was a
      significant difference in the average values of capillary blood and plasma blood
      (134.1 vs. 122.7 mg/dl, respectively). When the data were analyzed by ROC curve,
      the optimal level of capillary blood by Accu-Chek Advantage for performing a 100
      gm oral glucose tolerance test was 140 mg/dl (reference plasma glucose level of
      at least 140 mg/dl). The sensitivity specificity likelihood ratio for a positive
      test result and likelihood ratio for a negative test result were 93.8%, 83.6%,
      5.71 and 0.07, respectively. The potential advantages of capillary blood glucose
      screening are simple to use, cheap and convenient. CONCLUSION: Accu-Chek
      Advantage is suitable for screening gestational diabetes using the optimal
      threshold capillary glucose level of 140 mg/dl.

PMID- 19845233
TI  - Protection of radiocontrast induced nephropathy by vitamin E (alpha tocopherol):
      a randomized controlled pilot study.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) increases the likelihood of
      patient morbidity and mortality following coronary procedures. Contrast agents
      cause an acute deterioration in renal function via the generation of reactive
      oxygen species. The present study was designed to evaluate the administration of
      antioxidant vitamin E (alpha tocopherol) as a means of preventing CIN in these
      patients. MATERIAL AND METHOD: The authors conducted a prospective, double-blind,
      randomized and placebo-controlled trial in 103 patients with serum creatinine
      (SCr) levels > or = 1.2 mg/dL, baseline creatinine clearance levels < or = 60
      mL/min, and who had undergone coronary procedures. Alpha tocopherol (525 IU) or a
      placebo compound was administered orally at 48 hr, 24 hr, and in the morning
      prior to coronary procedures. RESULTS: CIN developed in 3 of 51 patients (5.88%)
      in the alpha tocopherol group and 12 of 52 patients (23.08%) in the placebo group
      (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.05 to 0.79; p = 0.02).
      The mean SCr increased significantly in the placebo group (from 1.67 +/- 0.53 to
      1.9 +/- 0.87 mg/dL, p = 0.02) but not in the alpha tocopherol group (from 1.62 +/
      0.44 to 1.64 +/- 0.59 mg/dL, p = 0.74). Patients with diabetes, anemia, or with
      contrast agent dosages greater than 120 ml exhibited significantly lower
      incidences of CIN development in the alpha tocopherol group than the placebo
      group (p < 0.05). CONCLUSION: Prophylactic oral administration of alpha
      tocopherol is capable of protecting against CIN in patients with chronic kidney
      disease undergoing elective coronary procedures.

PMID- 19845234
TI  - Autologous chondrocytes implantation with three-dimensional collagen scaffold.
AB  - OBJECTIVE: The authors report a patient with large traumatic knee cartilage
      defects treated with autologous chondrocytes implantation (ACI) in three
      dimensional collagen scaffold. MATERIAL AND METHOD: A patient with grade 3-4
      according to ICRS (International Cartilage Repair Society) Classification System
      was performed ACI with three-dimensional collagen scaffold. The two-stage
      procedure was performed First, the cartilage was arthroscopic harvested. The
      chondrocytes were isolated in the laboratory. Second, the chondrocytes were re
      implanted into the defects using three-dimensional collagen scaffold. The
      patients were clinically evaluated pre-operatively and post operatively and
      magnetic resonance imaging. The duration of follow-up was 12 months. RESULTS:
      There was no post operative complication. The clinical evaluations were
      excellent. The MRI showed the hyaline-like cartilage tissue formation at the
      defects. CONCLUSION: The autologous chondrocytes implantation with three
      dimensional collagen scaffold showed the excellent outcome. Long-term follow-up
      is required.

PMID- 19845235
TI  - The effectiveness and safety of intra-articular injection of sodium hyaluronate
      (500-730 kDa) in the treatment of patients with painful knee osteoarthritis.
AB  - BACKGROUND: Sodium Hyaluronate (500-730 kilodalton (kDa); Hyalgan) is recommended
      to administer intra-articularly once a week for 3-5 weeks in patients with
      osteoarthritis of the knee which its efficacy has been shown, from many clinical
      studies, to persist for at least 6 months. However only a few studies were done
      in Thai patients. OBJECTIVE: To assess the efficacy and safety of intra-articular
      Sodium Hyaluronate, administered once a week for four weeks (four injections) in
      Thai patients with painful Tibio-Femoral osteoarthritis of the knee over a six
      month period. MATERIAL AND METHOD: Thirty-one patients with painful knee
      osteoarthritis in grade I (32.3%) and grade II (67.7%) severity on Ahlback
      radiological criteria from Orthopedic Clinic in Bhumibol Adulyadej Hospital were
      included in this study. All patients were administered with 4-weekly injections
      of intra-articular Sodium Hyaluronate (500-730 kDa; Hyalgan; 20mg/2ml). Only
      paracetamol was permitted for escape analgesia. The efficacy parameters were the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain,
      stiffness and physical function, intake of paracetamol, and overall efficacy
      judgment by investigators and patients. The occurrence of adverse event was
      recorded at each visit. RESULTS: After the second injection of Sodium
      Hyaluronate, all WOMAC index revealed the significant improvement from baseline
      (p < 0.05). The WOMAC-VAS for pain at baseline, Day 14, 28, 84, and 168 were
      50.3, 33.3, 29.1, 23.1, and 21.4 mm respectively. At the end of study, most
      patients and investigators evaluated treatment efficacy as moderate to very
      effective. There was a decrease in paracetamol consumption from baseline until
      the last follow-up. Nine adverse events were recorded, which were transient
      events; most of them consisted of pain at injection site. No systemic or serious
      adverse event was reported. CONCLUSION: The results of this study showed the
      efficacy and safety of 4-weekly injections of Sodium Hyaluronate in the treatment
      of knee osteoarthritis in Thai patients over a six-month period.

PMID- 19845236
TI  - The relationship of anteroposterior, transepicondylar and posterior condylar axis
      of the femur: a Thai cadaveric study using digital measurement.
AB  - OBJECTIVE: To study the normal relationship of the anteroposterior (AP),
      transepicondylar (TE) and posterior condylar (PC) axis of cadaveric femoral bones
      using digital technology and special computer program. MATERIAL AND METHOD:
      Digital image of distal femur of 100 cadaveric bones of both sides and both sexes
      were taken using a special stand and clamp to ensure the same view and same
      distance from bone to camera. All still images were transferred into a specially
      developed computer program, then reference points were located by two observers,
      and were done twice at one week interval. The program reported the angle between
      AP-TE, AP-PC and TE-PC axes automatically. The data was then analyzed. RESULTS:
      The age of donor cadaveric bones ranged from 22 to 58 years (average 45.61 +/-
      7.73). The AP-TE, AP-PC and TE-PC angles were 92.43 +/- 2.07, 86.65 +/- 1.85 and
      5.79 +/- 1.26, respectively. The correlation coefficients of intra-observer
      reliability in observer 1 were 0.89, 0.87 and 0.91; in observer 2 were 0.92, 0.90
      and 0.87. The correlation coefficients of inter-observer reliability were 0.81,
      0.82 and 0.80. Limit agreement tests of AP-TE, AP-PC and TE-PC were 90.59%, 92.
      57% and 96.03%, in that order. CONCLUSION: Using digital technology, the normal
      relationship of AP, TE and PC axes of femur from cadaveric bone could be more
      accurately studied comparing with the previous studies performing measurement on
      plain film, CT scan or MRI using goniometer.

PMID- 19845237
TI  - Benefit of hydrocolloid SSD dressing in the outpatient management of partial
      thickness burns.
AB  - Silver sulfadiazine has been used as topical medication in the treatment of
      partial-thickness burns or secondary degree burns for many years. Pain during
      daily wound cleansing is the main problem. Urgotul SSD, a hydrocolloid dressing
      with silver sulfadiazine (SSD) has been reported to reduce infection and exhibit
      antimicrobial activity in burn wounds. The purpose of the present study was to
      compare the efficacy of Urgotul SSD and 1% silver sulfadiazine for treatment of
      partial thickness burn wounds. The authors reviewed 68 patients who had partial
      thickness burn wound less than 15% total body surface area (TBSA%) and were
      treated at Siriraj outpatient burn clinic during July 2005-December 2006. All
      patients were divided into two groups: Urgotul SSD treated group (34 patients)
      and 1% silver sulfadiazine treated group (34 patients). The two groups were
      compared by the demographic data including age, gender, % total body surface area
      (TBSA) burn, % TBSA deep burn, type of burn as well as percent of wound
      infection, total cost of wound dressing, pain medication, level of pain and time
      of wound healing. There were no differences in demographic data of age, % TBSA
      burn, % wound infection, total treatment cost of burn wound care (52 +/- 38 US$
      for Urgotul SSD versus 45 +/- 34 US$ for silver sulfadiazine treated group). Time
      of wound closure was significantly shorter in the Urgotul SSD treated group (10
      +/- 4 days in Urgotul SSD versus 12 +/- 6 in 1% silver sulfadiazine treated
      group) between both groups (p < 0.05). Average pain scores and pain medication in
      Urgotul SSD treated group was significantly lower than 1% silver sulfadiazine
      treated group (3 +/- 1 versus 6 +/- 2 and respectively, p < 0.05). All of the
      patients who developed wound infection responded well to targeted topical and
      oral antibiotic treatment. The authors conclude that Urgotul SSD has advantages
      of reducing pain symptom, pain medication requirement, increased patient
      convenience due to decreased time of follow-up at outpatient burn clinic,
      limiting the frequency of replacement of the dressing at comparable total cost
      and incidence of burn wound infection. The present study confirms the efficacy of
      Urgotul SSD in the treatment of partial thickness or secondary degree burn wound
      at the outpatient clinic.

PMID- 19845238
TI  - Spontaneous breathing trial with low pressure support protocol for weaning
      respirator in surgical ICU.
AB  - OBJECTIVE: Compare the effectiveness between spontaneous breathing trial with low
      pressure support protocol and liberal or non-protocol directed method. MATERIAL
      AND METHOD: The authors conducted a retrospective study involving 577 patients
      who were arranged and appropriate to weaning from mechanical ventilation on
      general surgical intensive care unit between July 1, 2004 to June 30, 2007. Two
      hundred and twenty two patients were weaned by their host surgeons or team
      (liberal group). Three hundred and fifty five patients underwent once daily
      spontaneous breathing trial with low-pressure support protocol. Patients assigned
      to this protocol had the pressure support level decreased to 5-7 cm of water for
      up to two hours each day. If signs of intolerance occurred, the process was
      restrained while patients who tolerated the two-hour trial without signs of
      distress were extubated. The authors collected demographic data, cause of ICU
      admission, APACHE II score at arranged time to weaning, weaning process time,
      ventilator day, and ICU length of stay. RESULTS: There was statistical difference
      between liberal and protocol in age (59.2 +/- 19.3 vs. 55.6 +/- 19.8; p = 0.03)
      but there was no statistical difference in gender (male 74.3 vs. 67.9%; p = 0.2)
      and APACHE II score at arranged time to wean (14.7 +/- 7.4 vs. 15.3 +/- 6.3; p =
      0.2). The median (inter-quartile) range duration of weaning process (29.5 (48)
      vs. 2.25 (2.9), p < 0.001), ventilator day (3 (4) vs. 2 (3), p < 0.001), and
      length of ICU stay (5 (5) vs. 3 (3), p < 0.001) were shorter in the protocol
      group than the liberal group. Multivariate linear regression model also revealed
      significantly less duration of weaning process in the protocol group than the
      liberal group in terms of weaning time (-63.6 (-74.7 to -2.6) hours), ventilator
      day (-3.0 (-3.7 to -2.2) days), and length of ICU stay (-2.9 days (-3.7 to -2.0);
      p < 0.001) (95% confidence interval). CONCLUSION: Spontaneous breathing trial
      with low-pressure support protocol for liberal from mechanical ventilator was
      effective to reduce weaning time, ventilator day, and length of ICU stay in
      general surgical intensive care units.

PMID- 19845239
TI  - Bilateral scrotal flap: pedicle and dimension of flap in cadaveric dissections.
AB  - Penile paraffinoma is not uncommon among Thai males. The definite treatment
      involves the complete removal of skin and subcutaneous tissue infiltrated by the
      foreign material and resurfacing in the penile shaft with skin graft or scrotal
      flap in severe cases. In the present study the authors undertook an anatomical
      investigation of external pudendal vessels and scrotal skin in 5 soft cadavers.
      The authors found that the anterior scrotal artery branching from the external
      pudendal artery at the point 2-2.7 cms. from midline at pubic symphysis level and
      running in the internal spermatic plane. Anterior scrotal artery supplied scrotal
      skin 62.5-100% (mean 75.9%) in anteroposterior dimension and 66-100% (mean 88%)
      in superoinferior dimension. The authors recommended that this flap must elevate
      deep to the internal spermatic plane, just close to tunica vaginalis and the
      dimension of flap should not be more than 62.5% in anteroposterior and 66% in
      superoinferior dimension.

PMID- 19845240
TI  - Effects of pregabalin on post operative morphine consumption and pain after
      abdominal hysterectomy with/without salphingo-oophorectomy: a randomized, double
      blind trial.
AB  - BACKGROUND: Achieving post operative pain management is difficult with the use of
      only opioids analgesia. Multimodal pain management is a method to improve post
      operative analgesia with minimal side effects. Pregabalin has an analgesic and
      opioids sparing effects in post operative analgesia. OBJECTIVE: The objective of
      the present study was to evaluate the effect of premedication with pregabalin 300
      mg compared with lorazepam 0.5 mg on post operative morphine consumption in women
      undergoing abdominal hysterectomy with/without salphingo-oophorectomy. MATERIAL
      AND METHOD: Eighty ASA I-III, aged 18-65 year patients undergoing elective
      abdominal hysterectomy with/without salphingo-oophorectomy were randomized to
      receive either lorazepam 0.5 mg or pregabalin 300 mg 1 hr before surgery.
      Anesthesia was induced with thiopental (3-5 mg/kg) and atracurium (0.6 mg/kg) and
      maintained with sevoflurane with a fresh gas flow of 2 L/min (50% N2O in O2) and
      morphine 0.1-0.2 mg/kg. All patients received patient-controlled analgesia with
      morphine with a 1 mg incremental dose, 5-min lockout interval, and 4-hr limit of
      40 mg post operative. Patients were studied at 0, 1, 4, 12 and 24 hours post
      operatively for verbal numerical rating scale (VNRS), morphine consumption,
      satisfaction score and side effects. RESULTS: The VNRS scores of the pregabalin
      group were significantly lower than the control group at 1, 4, 12 and 24 hours
      after surgery. The total morphine consumption at 24 hours post operatively of
      pregabalin group (7.11 +/- 5.57) was significantly lower than the control group
      (21.18 +/- 7.12) (p < 0.01). There were no differences between groups in
      somnolence and dizziness (p = 0.93) and nausea-vomiting (p = 0.11). The
      satisfaction score was higher in the pregabalin group. CONCLUSION: A 300 mg
      pregabalin administered 1 hr preoperatively before abdominal hysterectomy
      with/without salphingo-oophorectomy significantly reduced morphine consumption,
      VNRS pain score and improved satisfaction score at 24 hr post operatively without
      any significant differences in side effects. Pregabalin is an alternative
      combination to opioids as multimodal analgesia.

PMID- 19845241
TI  - Population pharmacokinetics of digoxin in Thai pediatric patients.
AB  - OBJECTIVE: To determine the digoxin population pharmacokinetic parameters and
      influence of various factors on pharmacokinetic parameters in Thai pediatric
      patients with heart disease. MATERIAL AND METHOD: The present study was an
      analytical cross-sectional study design and population pharmacokinetic modeling
      study. The data of 130 patients and 264 samples with an age range of 0.1-15.7
      years-old were collected during routine care. Blood samples were drawn at various
      times after administration. All patients received digoxin administration with a
      dose ranged of 1.7-13.6 microg/kg/day at Queen Sirikit Heart Center; Khon Kaen
      University, Thailand. Population pharmacokinetic modeling was developed from
      digoxin data by using NONMEM program (Version V) according to one-compartment of
      subroutine ADVAN2 TRANS2 model. RESULTS: Weight, age, height and the presence of
      congestive heart failure (CHF) were significant covariates on CL. Weight and the
      presence of CHF were significant covariates on Vd. The final population model of
      CL and Vd in pediatric patients were as follows: CL/F (L/h) for infant (0-1 year)
      = 0.322 * WT (kg); CL/F (L/h) for children (> 1 year) = (0.138 * WT(kg) + 0.0319
      * HT (cm) * 0.765CHF; and Vd/F (L) for all ages = 9.27 * WT (kg) * 1.75CHF. The
      interindividual variability of CL/F, Vd/F and intraindividual variability with
      proportional error model were 31.48, 35.56, and 41.7%, respectively. In the
      validation data set (57 samples), predictive performance in terms of bias (ME)
      and precision (RMSE) were -0.049 ng/mL (95% CI: -0.118-0.020) and 0.269 ng/mL
      (95% CI: 0.216-0.312), respectively. CONCLUSION: This simple final population
      model of Vd and CL can be used in clinical practice for estimating appropriate
      dosage regimen of loading dose and maintenance dose, respectively. Current
      weight, height, and presence of CHF should be taken into account when designing
      dosage regimen for individualized pediatric patients.

PMID- 19845242
TI  - Finite element analysis of bone around a dental implant supporting a crown with a
      premature contact.
AB  - OBJECTIVE: To investigate the influence of a premature contact caused by an
      implant-retained crown (IRC) on stress and strain distributions in bone
      surrounding the implant using the finite element method. MATERIAL AND METHOD: A
      3D finite element (FE) model of a section of a mandible with a single tooth
      dental implant, an IRC, and two adjacent teeth was created. Three rigid plates
      were used to represent the antagonist teeth. Modeling the antagonist teeth using
      the rigid plates removed the necessity to create FE models for the antagonist
      teeth, their periodontal ligament, and the maxilla. Moreover, this new approach
      also allowed the premature contact height to be easily varied by changing the
      positions of the rigid plates. In the present study, premature contact heights of
      0, 50, 100, 150, 200 and 250 microm were considered. The FE contact analysis was
      employed. All materials were assumed to be linear elastic and isotropic. RESULTS:
      The magnitudes of von Mises stresses in the bone change drastically when there
      was a premature contact. For example, the von Mises stress increased from 9.68
      MPa in the case with no premature contact to 49.92 MPa in the case with the
      premature contact height of 50 microm. In addition, the magnitude of the major
      principal strain in the marginal bone reached the pathologic overload of 4000
      microepsilon when the premature contact height was 100 microm or higher.
      CONCLUSION: The influence ofpremature contacts is very high and the premature
      contact height of an IRC over 100 microm should be avoided as much as possible to
      provide longevity of dental implants.

PMID- 19845243
TI  - Cadmium-exposed population in Mae Sot District, Tak Province: 2. Prevalence of
      renal dysfunction in the adults.
AB  - BACKGROUND: In 2004, 7,697 cadmium-exposed persons aged 15 years and older in Mae
      Sot District, Tak Province, Thailand, were screened for urinary cadmium levels
      and 554 cases (7.2%) had > or = 5 microg/g creatinine. OBJECTIVE: The present
      study reported the prevalence of renal dysfunction among those with high urinary
      cadmium (> or = 5 microg/g creatinine). MATERIAL AND METHOD: The study persons
      were interviewed and examined for detection of renal dysfunction. Venous blood
      and second morning urine were obtained from each subject for microscopic analysis
      and biochemistry measurements. RESULTS: Of the 527 examined persons, 14.2% had
      urinary beta2-microglobulin excretion between 300 and 999 microg/g creatinine,
      and 19.9% contained > or = 1,000 microg/g creatinine. About 21.1% had serum
      creatinine concentrations between 1.1 and 1.4 mg/dl and 4.2% contained > or = 1.5
      mg/dl. Low glomerular filtration rate (GFR < 60 ml/min/1.73 m2 body surface area)
      was present in 16.9% of the study persons. Of the persons surveyed, 75.3% had the
      fractional excretion of phosphate > 5% and 24.7% contained the fractional
      excretion of potassium > 10%. The overall prevalence rates of hypertension and
      urinary stones in the study population were 31.3% and 8.9%, respectively.
      Excretion of urinary beta2-microglobulin significantly increased with increasing
      urinary cadmium levels. Both increased serum creatinine and decreased GFR
      appeared to be associated with increasing urinary cadmium although the difference
      was not statistically significant. There were no significant associations between
      urinary cadmium levels and excretion of urinary protein, urinary calcium,
      hypertension, and urinary stones. CONCLUSION: Excessive exposure to cadmium might
      produce renal dysfunction among the present study population. Increased urinary
      excretion of beta2-microglobulin is a good indicator of renal tubular dysfunction
      among persons with excessive cadmium exposure.

PMID- 19845244
TI  - Prevalence and management of poststroke spasticity in Thai stroke patients: a
      multicenter study.
AB  - OBJECTIVES: To study the prevalence, associated factors and management of
      poststroke spasticity in two muscle groups namely elbow flexor and knee flexor.
      MATERIAL AND METHOD: The Thai stroke rehabilitation registry (TSRR) was conducted
      among 9 rehabilitation centers. All subjects received the conventional
      rehabilitation program until they reached their rehabilitation goals or discharge
      criteria. The Brunnstrom motor recovery stage, Barthel Index, Thai Mental State
      Examination, Modified Ashworth Scale (MAS), and WHOQOL-BREF-Thai (26 items)
      questionnaires were used to assess the motor recovery, functional disability,
      cognition, spasticity and quality of life on admission respectively. The
      management of spasticity was also recorded. RESULTS: There were 327 patients with
      a mean age of 62.2-years-old participating in the study. The prevalence of
      poststroke spasticity was 41.6%. Among these the prevalences of spasticity of
      both elbow and knee flexors was 31.2% and of either elbow or knee flexor were
      4.9% and 5.5% respectively. Spasticity with MAS grade 1 was found in the
      majority. The patients with spasticity had a significantly longer time to
      rehabilitation admission interval after the stroke (p = 0.049), had the
      Brunnstrom motor recovery stages of arm (p < 0.001), hand (p = 0.003) and leg (p
      < 0.001) significantly lower than the no spasticity group. The factor associated
      with spasticity was Brunnstrom motor recovery stage 2 and 3 of the arm with the
      odds ratio being 6.1 (95% CI = 2.5-14.9) and 3.5 respectively (95% CI = 1.3-9.2).
      Management of spasticity was demonstrated in 83 patients (25.4%). Therapeutic
      exercise, oral antispastic medication and assistive device were the first three
      managements frequently prescribed respectively. CONCLUSION: Spasticity was a
      common complication after stroke. Although the prevalence was quite high,
      spasticity with MAS grade 1 was found in the majority of cases. The associated
      factor was the Brunnstrom motor recovery stage of the arm. Therapeutic exercise
      was the mainstay of the management.

PMID- 19845245
TI  - National survey on smoking situation in Royal Thai Police.
AB  - OBJECTIVE: Study current smoking situation among Royal Thai Police officers
      nationwide. MATERIAL AND METHOD: 20,000 questionnaires about smoking behavior,
      amount of cigarettes smoked per day, and staging of smoking cessation were
      distributed between March and August 2008 to 1) the Office of the Top Management,
      2) every bureau nationwide, 3) every division of any police bureau, 4) six
      biggest police stations from every division, and 5) three subdivisions from every
      division in supporting bureau. The Police General Hospital, Police Education
      Bureau, Police Cadet Academy, Office of Inspector General, and Office of the
      Royal Court Security Police were excluded from this survey. RESULTS: Of all
      20,000 questionnaires distributed, 14,231 completed questionnaires were received
      during the five-month study period. Nationwide, 30.9% of Thai police smoke, 33.4%
      of male police officers smoke while only 3.3% of female police officers do. Among
      five groups classified by organizational structure, the Metropolitan Police
      Bureau has the highest smoking rate of 33.9%. Detective police smoking rate of
      40.3% is the highest among field of police work. Ten point one percent of the
      police officers who currently smoke are addicted to nicotine in the high level of
      20 or more cigarettes per day. However 60.4% of the police officers who currently
      smoke attempt to quit smoking at least once a year but fail and 84.7% of the
      entire police officers agree with the smoke-free workplace policy, which has
      already been implemented and 76.0% of the police officers who currency smoke
      agree with the 100% smoke-free police station policy. CONCLUSION: The smoking
      rate of Thai police is higher than the average smoking rate of Thai population.
      In order to decrease the smoking rate among Thai police, the 100% smoke-free
      police station policy should be implemented. This policy aims to counsel police
      officers who currently smoke about nicotine withdrawal symptoms in the short
      term, and to alter behavior and attitude about smoking in the long term.

PMID- 19845246
TI  - Factors related to missed appointment at psychiatric clinic in Songklanagarind
      Hospital.
AB  - OBJECTIVE: To determine the associated factors of missed appointments among
      psychiatric clients. MATERIAL AND METHOD: All medical records of the psychiatric
      patients in the year 2007, age more than 15-years-old, were reviewed
      retrospectively. The variables included age, occupation, disease/condition, type
      of medical welfare, distance from hospital, attending physician category, and
      number of visit scheduled and completed. RESULTS: Around one-fifth of 11, 753
      (2,423) (20.6%) were missed appointments. Types of therapist (psychiatric
      residents), non-welfare clients, and distance from the hospital of more than 50
      kilometers significantly (p < 0.01) increased the rate of missed appointment.
      CONCLUSION: The surveillance of the appointment system implied the visit/non
      visit rate, and adherence to the follow-up appointment, as well as had indirectly
      reflected the client's satisfaction, and barriers of medical services.

PMID- 19845247
TI  - Acute suppurative thyroiditis with thyrotoxicosis.
AB  - BACKGROUND: Acute suppurative thyroiditis (AST) is a rare condition in children,
      and most children with AST usually have normal thyroid function. OBJECTIVE: To
      report a case of thyrotoxicosis complicating AST in a child. CASE REPORT: A 6
      year-old boy with AST presented with the unusual clinical features of severe
      thyrotoxicosis. Two palpable masses were found to be of firm to hard consistency
      with tenderness without any acute inflammatory signs on the overlying skin of the
      thyroid gland. The diagnosis of AST was confirmed by ultrasonography and fine
      needle aspiration. Thyroid function tests were normal within a week after
      antibiotic treatment and surgical drainage. CONCLUSION: Transient thyrotoxicosis
      complicating AST is very rare in children. Awareness of this unusual complication
      is important to avoid inappropriate treatment of hyperthyroid disease.

PMID- 19845248
TI  - Delayed encephalopathy and cognitive sequelae after acute carbon monoxide
      poisoning: report of a case and review of the literature.
AB  - Serious delayed encephalopathy and cognitive sequelae following acute carbon
      monoxide intoxication constitutes a rare and a distinct entity. A case of delayed
      encephalopathy and cognitive sequelae after acute carbon monoxide poisoning is
      presented. The patient is a 50-year-old Thai female with a history of carbon
      monoxide poisoning during her vacation tour in Arizona in winter. She developed
      encephalopathy 4 weeks after recovery from the acute stage. Her MRI-brain found
      abnormal white matter change of cerebral hemispheres bilaterally and abnormal
      signal intensity at both putamens and caudate nuclei. She regained some
      improvement in her memory and other cognitive function after 4 weeks of treatment
      including hyperbaric oxygen therapy (HBOT).

PMID- 19845249
TI  - Laparoscopic extravesical ureteral reimplantation for iatrogenic distal ureteral
      stricture.
AB  - OBJECTIVE: The authors describe their experience with laparoscopic extravesical
      neoureterocystostomy for iatrogenic distal ureteral stricture using a
      transperitoneal intracorporeal freehand suturing technique. MATERIAL AND METHOD:
      Three patients with distal ureteral strictures underwent laparoscopic
      transperitoneal extravesical ureteral reimplantation. A 77-year-old male
      underwent a Lich-Gregoir antireflux ureteral reimplantation following
      complications arising from transurethral resection of the prostate, and two
      females, aged 28 and 34 years, underwent refluxing ureteral reimplantation with
      concurrent psoas hitch after gynecologic surgery. The authors reviewed patient
      records to assess peri- and postoperative outcomes following definitive
      laparoscopic management of stricture segments. RESULTS: All procedures were
      completed entirely using a laparoscopic approach. No intra- or post-operative
      complications were reported. Operative times ranged between 180-250 minutes and
      mean blood loss was 50-150 ml. The mean time to restarting oral intake was 12
      hours. Pathological evaluation confirmed benign lesions in each case and follow
      up imaging confirmed satisfactory functional results. CONCLUSION: Laparoscopic
      extravesical neoureterocystostomy for iatrogenic distal ureteral strictures is a
      safe and efficacious procedure. Larger cohorts and longer-term results are
      required before this technique is considered first-line therapy in this patient
      group.

PMID- 19845250
TI  - Paradoxical embolism in bilateral total knee arthroplasty: a case report.
AB  - Paradoxical embolism is defined as venous thrombosis causing systemic
      embolization through a right-to-left shunt. We, herein, report a case of
      bilateral total knee arthroplasty and developed paradoxical embolism caused by
      patent foramen ovale. A sixty-two-year-old female had a simultaneous, total knee
      arthroplasty for primary osteo-arthritis. A pulmonary emboli was suspected on the
      thirteenth post operative day. Two days later, acute arterial insufficiency at
      her leg was suspected. An embolectomy and intra-operative tranesophageal
      echocardiogram was performed. It showed patent foramen ovale (PFO) 2-3 mm. Five
      days after embolectomy, she developed infarction lesion at the right occipital
      area. The foramen ovale was closed with a closure device nineteen days later. The
      patient eventually could walk using a walker. She was discharged thirty-six days
      after the operation.

PMID- 19845252
TI  - [73-year-old patient with a constitutional syndrome and abdominal pain].

PMID- 19845251
TI  - Tetramethylenedisulfotetramine contaminated milk powder induced status
      epilepticus in two siblings and two dogs.
AB  - A cluster of patients with tetramethylenedisulfotetramine (TETS) intoxication was
      reported in Thailand. Two siblings, a-six-month-old boy and a-four-year-old girl,
      and their domestic dogs presented with status epilepticus within 10 minutes after
      ingesting milk prepared from the same tin container of milk powder. Although the
      cases showed normal neurodevelopment at one-year follow-up, physicians should be
      informed of this lethal neurotoxic agent, especially in an era of terroristic
      activity.

PMID- 19845253
TI  - [Cutaneous abscess].

PMID- 19845254
TI  - [Helicobacter pylori: some epydemiological questions in Latin America after
      twenty-five years].

PMID- 19845255
TI  - [Pablo Luis Mirizzi].

PMID- 19845256
TI  - [Prospective, double-blind study of topical phenylephrine treatment for nocturnal
      fecal incontinence in patients after ileoanal pouch construction].
AB  - PATIENTS: Fecal incontinence has been reported in 5.5% to 45% of patients after
      ileoanal pouch construction, predominantly at night. It has been shown that
      alpha1-adrenergic agonists as phenylephrine increase anal sphincter pressure in
      healthy volunteers and in patients with idiopathic fecal incontinence. The median
      duration of action of topical phenylephrine is seven hours. Carapeti et al have
      demonstrated its usefulness in patients after ileoanal pouch construction.
      OBJECTIVE: To demonstrate that the administration of a single dose of topical 10%
      phenylephrine at night is effective for the treatment of nocturnal anal
      incontinence in this group of patients. PATIENTS AND METHODS: We randomized 12
      patients in two groups. Group A (control) received a placebo cream and group B
      received a 10% phenylephrine cream. The study was prospective, randomized and
      double-blind. RESULTS: There were no significant differences between the two
      groups in age, follow-up time since the closure of ileostomy and pre-treatment
      and intra-treatment leaks. Control group had 7 episodes of incontinence pre
      treatment and 9 intra-treatment. Treated group had 3 and 5.4, respectively. (p =
      NS) No patient had side effects. CONCLUSIONS: Given the small number of patients
      included, we can not yet rule out that topical 10% phenylephrine is useful for
      the treatment of nocturnal fecal incontinence in patients after ileoanal pouch
      construction. It would be necessary to continue with studies, increasing the
      number of patients treated with this drug, in order to have a better evidence of
      its clinical utility.

PMID- 19845257
TI  - Chromogranin A as a biochemical marker for the management of neuroendocrine
      tumors: a multicenter study developed in Argentina.
AB  - Elevated circulating levels of chromogranin A (CgA) are found in the
      neuroendocrine tumors (NETs), but diagnostic usefulness of this marker is still
      debatable. To assess the role of CgA for the identification and follow up of
      gastroenteropancreatic neuroendocrine tumors (GEP-NET), a multicenter prospective
      longitudinal study has been carried out in Argentina. CgA was measured by RIA in
      119 histologically proven GEP-NET patients and in 39 healthy controls. A cutoff
      value of 2.8 nmol/L was established from a receiver-operating characteristic
      (ROC) curve, as discriminating between controls and patients with active disease
      (specificity 100% and sensitivity 92.3%). CgA levels were higher in functioning
      than in no functioning tumors (median 55 nmol/L vs 5 nmol/L, p < 0.05).
      Metastases were present in 83 patients and their CgA levels were significantly
      higher than levels in the 36 patients without metastases (median 44 nmol/L vs 64
      nmol/L, p < 0.0001). CgA levels are strongly correlated with tumor metastatic
      spread. Sensitivity differed between patients with localized disease (median 6
      nmol/L), extensive disease (median 22 nmol/L) and very extensive disease (median
      44 nmol/L) (p < 0.001). In conclusion, due to its high sensitivity and
      specificity, CgA is useful in a newly discovered GEP-NET especially when no
      abnormal hormone secretion can be demonstrated. CgA levels were significantly
      higher in functioning tumors than in non-functioning tumors and increased with
      metastatic spread. If serial evaluation of CgA levels is sufficient for the
      detection of tumor growth changes remains to be prospectively demonstrated.

PMID- 19845258
TI  - [Primary anal tuberculous fissure].
AB  - The anal tuberculous (TBC) fissure is infrequent. For this reason diagnosis is
      difficult. A case of a female adult patient with anal TBC fissure that consults
      for bleeding and perianal pain is presented. The perianal tuberculosis is a rare
      manifestation of the general disease. A routine biopsy must be performed, with
      the corresponding histopathologic study. A specific origin should be suspected
      when an anal chronic fissure, painful and bleeding, without response to the
      habitual treatment, is found. The primary TBC fissure can be cured with the
      administration of three drugs during 3 to 4 months.

PMID- 19845259
TI  - [Choledochal cyst IV A type with primary ductal stricture].
AB  - Type IV A choledochal cyst is a very uncommon disease, characterized by
      congenital cystic dilatation of the biliary tree extending to the intrahepatic
      biliary channels also. A case of a 19-year-old female with jaundice and abdominal
      pain is reported. The patient underwent a thorough clinical, laboratory and
      imaging examination. Computerized tomography and magnetic
      cholangiopancreatography revealed a 13.5 cm choledochal cyst with intrahepatic
      involvement. Excision of the extrahepatic part of cyst was combined with a Roux
      en-Y hepaticojejunostomy. A ductal stricture was discovered at the distal part of
      extrahepatic cyst. There were no perioperative and late complications in the
      follow-up.

PMID- 19845261
TI  - [Adverse effects of proton pump inhibitors].

PMID- 19845260
TI  - [Latin American contribution to the study of Helicobacter pylori].
AB  - We have reviewed Lilacs, PubMed and Google searching for original articles
      related to Helicobacter pylori published by Latin American investigators from
      2003 to 2008. Contributions in the following fields by countries are: Molecular
      biology: Brasil, Chile, Colombia, Peru y Venezuela. EPIDEMIOLOGY: Argentina,
      Brasil, Colombia, Cuba, Peru y Venezuela. DIAGNOSTIC METHODS: Argentina, Bolivia,
      Brasil, Chile, Costa Rica, Colombia, Mexico, Peru y Venezuela. Helicobacter
      pylori and gastroduodenal diseases: Brasil, Cuba, Peru y Venezuela. Helicobacter
      pylori and extra digestive diseases: Brasil, Colombia and Venezuela. Pediatrics:
      Brasil, Cuba y Venezuela. TREATMENT: Argentina, Brasil, Chile, Colombia, Costa
      Rica, Mexico, Peru y Venezuela.

PMID- 19845262
TI  - [Anastomotic leak following colorectal surgery: incidence, risk factors and
      treatment].
AB  - The aim of this study was to assess the incidence and identify the risk factors
      associated with colorectal anastomotic leakage. A further objective was to
      investigate the therapeutic choices. We reviewed the clinical files of 124
      patients who underwent mechanical end-to-end anastomosis after colorectal
      resection during the period 2000-2007. The mean age was 66.9 years and the
      male:female ratio was 1.2:1. Indications for surgery were malignant neoplasms in
      109 cases (87.9%) and benign disease in 15 cases (12.1%). The anastomosis was
      always performed in an elective setting in the framework of a procedure of one or
      more stages (87.9% and 7.3% respectively). A pelvic drain was positioned in a
      routine manner and no protective ileostomies were constructed. Among the various
      risk factors, co-morbidities, ASA risk and low anastomotic level were the most
      important we examined. Student's t-test, the Chi-square test and Fisher's test
      were used for comparative univariate analysis, with significant results for p <
      or = 0.05. The incidence of anastomotic leak was 10.5% (13/124), but only 4.8%
      (6/124) required a second operation or failed to heal with simple conservative
      therapy. The pelvic drain was always effective in allowing the early diagnosis of
      leakages and limiting the spread of peritoneal inflammation. Mortality was 1.6%
      (2/124) overall, but, if leakages alone were considered, it increased to 15.4%.
      Among the risk factors examined, only low anastomotic level was confirmed by
      statistical analysis. In conclusion, the study confirms low anastomotic level as
      a negative prognostic factor for the healing of colorectal anastomosis. The
      pelvic drain proved to be effective in allowing early diagnosis and conservative
      management of leakages.

PMID- 19845263
TI  - [Prognostic significance of the Mandard TRG classification after induction
      therapy in carcinoma of the oesophagus and cardia].
AB  - Mandard's tumor regression grade (TRG) is widely used to evaluate the
      pathological response to induction therapy with concurrent chemoradiotherapy in
      cancer of the oesophagus or gastro-oesophageal junction. The aim of this study
      was to evaluate the prognostic significance and clinical applicability of TRG.
      From 2000 to 2007, 108 patients with squamous cell carcinoma of the oesophagus
      (57 cases) or Siewert type I and II adenocarcinoma of the cardia (51 cases) were
      treated with induction chemoradiotherapy followed by surgery in the 1st Division
      of General Surgery of the University of Verona. The treatment was identical for
      all patients and consisted of cisplatin, 5 FU and docetaxel together with 50 Gy
      of concurrent radiotherapy. The treatment-induced response was evaluated by TRG.
      Fifty-one, 24, 17, 9 and 7 patients were classified, respectively, as TRG1, 2, 3
      4 and 5. Fifty-two patients died of the disease. Disease-related survival
      decreased with the increase in TRG class in node-negative patients (p < 0.001),
      while in N+ patients it was poor, irrespective of TRG class (p = 0.241). Mandard
      TRG is therefore useful for staging patients undergoing preoperative
      chemoradiotherapy, because it displays high prognostic significance. In our
      study, however, N was the main prognostic factor and for this reason it is
      mandatory to consider nodal status along with TRG. Moreover, among N negative
      patients, the prognosis of each different TRG class is statistically different
      and for this reason different TRG classes cannot be grouped together.

PMID- 19845264
TI  - [Laparoscopic splenectomy in haematological diseases: short- and medium-term
      results in thirty initial cases].
AB  - In 1991 Delaitre and Maignien described the first laparoscopic splenectomy, since
      when a rapid spread of this technique has been observed and the procedure has
      become the gold standard in the surgical management of benign and malignant
      haematological diseases. In the present study, the results of the first 30
      laparoscopic splenectomies performed at the Division of General Surgery of the S.
      Eugenio Hospital of Rome are reported. The operations were performed in patients
      with benign (27 cases) and malignant (3 cases) haematological diseases, treated
      in the Regional Haematological Centre of the same hospital. The procedures were
      carried out according to criteria corresponding to those recently described in
      the guidelines of the European Association for Endoscopic Surgery. As regards the
      results, two procedures (6.7%) were converted to open surgery. One postoperative
      haemorrhage was observed, requiring a laparoscopic reoperation for haemostasis.
      No other major local or general complications were observed. Mortality was nil.
      The mean postoperative hospital stay was 4.2 days (range: 4-8 days). Medium-term
      surgical and haematological results were excellent. Laparoscopic splenectomy is
      the surgical gold standard, but should be performed in advanced centres in close
      cooperation with a haematology centre. The procedure is indicated in all patients
      who are candidates for splenectomy, with the sole exception of those affected by
      portal hypertension or with general contraindications to laparoscopy. In advanced
      centres, better early and late results can be achieved, in addition to the well
      known benefits of the minimally invasive technique, particularly in aesthetic
      terms, which in younger patients affected by benign haematological pathologies
      are very important.

PMID- 19845265
TI  - [Emergency laparoscopic cholecystectomy in the treatment of acute cholecystitis:
      when and how?].
AB  - Optimal surgical timing and operative technique in the treatment of acute
      cholecystitis are of major importance and are still debatable issues. We report
      the results of our study on the timing of surgery in a consecutive series of 163
      patients treated in the emergency setting for acute cholecystitis over the period
      from 1998 to 2008. Early surgery and the partially downwards laparoscopic
      cholecystectomy technique provide a safe and effective way of treating these
      patients and preventing major complications. The mean time period between onset
      of symptoms and surgery was 69.2 hrs, with a median value of 53 hrs. The mean
      operative time was 63.9 min, with a conversion rate of 0.6% and a specific
      complication rate of 1.22%. The mean postoperative hospital stay was 3.2 days.
      The timing of surgery (measured in hours) and operative time (measured in
      minutes) were recorded and analysed to verify whether or not there was a
      statistically significant relationship between these two variables and establish
      the best timing for surgery. Our results show a linear relationship between
      operative time and the timing of surgery. Moreover, at the cut-off point of 57
      hrs, the later subgroup (over 57 hrs) had a two-fold increase in operative time
      compared to the earlier subgroup. At more than 60 hrs approximately from the
      onset of symptoms, the pathological changes in the surgical target begin, with
      increasing rapidity, to present a troublesome challenge to the surgeon, making
      laparoscopic cholecystectomy for acute cholecystitis more difficult and less safe
      than when performed earlier.

PMID- 19845266
TI  - [Surgical approach in the management of oesophageal tumours: considerations based
      on therapeutic results].
AB  - Over the last two decades, oesophageal cancers, although considered among the
      most malignant visceral tumours, have witnessed a gradual increase in survival
      rates at a distance after surgery. The aims of the study were to present the
      results of our surgical approach and, on this basis, to discuss a number of
      considerations regarding the type of intervention to be adopted. In a
      retrospective study we recruited 105 patients with oesophageal cancer treated
      with various types of oesophageal resection, with or without thoracotomy, in the
      Division of General Surgery of the Civic Hospital of Sondrio. The postoperative
      mortality rate was 12%, with 40.2% of non-lethal complications. The average
      overall survival, whether in patients R0 or not, was 31.2 months (range: 1-167),
      with actuarial survival rates of 63.2% at one year, 30.3% at three years and
      22.1% at five years. This was not significantly influenced by the type of surgery
      or by the location or histology of the cancer, while TNM stage, degree of
      parietal infiltration and the presence or absence of lymph-node metastases were
      significant factors. Although we limited the lymphadenectomy to "standard or
      extended two-field" operations, our overall survival at five years was similar to
      that of surgeons advocating much more extensive lymphadenectomy. In our case most
      of the relapses occurred at the systemic level and in the short term, on average
      after 12.7 months, meaning that micrometastases were probably already present at
      the time of intervention (82.4% of these patients, in fact, had stage N1
      cancers). We prefer cervical anastomosis owing to the possibility it affords of
      greater oesophageal resection and to its relative safety in case of dehiscence.
      We always perform a right cervicotomy, which allows us to avoid having to move
      the patient on the operating table and to have fewer injuries to the recurrent
      nerve.

PMID- 19845267
TI  - [Role of endoanal ultrasonography in reducing anal fistula recurrence].
AB  - The aim of surgical treatment of fistula-in-ano is to eradicate the suppurative
      process permanently without compromising faecal continence. The appearance of a
      recurrence of fistula-in-ano is often due to non-identification of the internal
      opening by the surgeon, and to the presence of complex fistulae. We evaluated the
      clinical course of 214 patients in a randomised. controlled trial with respect to
      the recurrence rate of anal fistula with or without preoperative endoanal
      ultrasonography. In this study we demonstrate that endoanal ultrasonography was
      the most accurate diagnostic modality for detecting internal opening and complex
      fistulae. Therefore, endoanal ultrasonography is reliable and useful in the
      preoperative assessment of anal fistula, and particularly for decreasing the
      recurrence rate of this disease.

PMID- 19845268
TI  - [Laparoscopic lavage and drainage in the surgical treatment of diverticular
      disease complicated by peritonitis].
AB  - The treatment of peritonitis complicating diverticular disease of the colon is
      yet to be universally regarded as established practice and major differences in
      management are to be noted in the various surgical institutions. In the emergency
      setting, the minimally invasive approach is used by few surgeons and the most
      frequent therapeutic options are sigmoid resection with primary anastomosis (with
      or without a diverting stoma) and Hartmann's procedure. The Authors report their
      preliminary experience (13 cases) with laparoscopic lavage and drainage without
      colonic resection in diverticulitis complicated by peritonitis and describe the
      technical details of the surgical procedure. They conduct a systematic review of
      the literature and, on the basis of their latest experience, compare the results
      of the traditional resective operations (resection with primary anastomosis and
      Hartmann's procedure) with those of laparoscopic conservative and non-resective
      treatment. Laparoscopic non-resective procedures reduce the frequency and
      severity of the surgical complications, as well as the hospital stay and costs of
      treatment. In conclusion, laparoscopic lavage and drainage can be used in the
      majority of patients, with excellent prospects of recovery, without disabling
      stomas, in a single operative stage.

PMID- 19845269
TI  - [Usefulness of plug test for the intraoperative staging of rectal mucosal
      prolapse].
AB  - Rectal mucosal prolapse is characterised by protrusion of the rectal mucosa alone
      in the anal lumen. To correctly establish the intraoperative stage of rectal
      mucosal prolapse the authors performed a test based on the intrarectal
      introduction of a large-sized hydrophilic plug, to be extracted later from the
      anal canal. A total of 40 patients with proctological symptoms and with a
      diagnosis of rectal mucosal prolapse were submitted, in the outpatient setting,
      to a minimally invasive test with a small plug and later, in the preoperative
      stage, in patients under anaesthesia, using a plug entirely inserted into the
      rectal lumen and extracted via the anus. The same procedure was performed after
      surgery to verify the results of the excision. In all cases the plug test used in
      the preoperative stage permitted the perfect surgical evaluation of the extent of
      the prolapse. The plug test revealed a mucosal prolapse occupying 25% of the anal
      circumference in 10 patients, up to 50% in 20 patients and more than 50% in 10
      patients. The first 30 patients were treated with the transfixed stitch
      technique, while for the others the Longo surgical technique was preferred. The
      plug test for the preoperative and postoperative evaluation of rectal mucosal
      prolapse is an effective tool for obtaining a more precise indication as to the
      optimal surgical intervention and for verifying the radicality of the surgical
      excision. The plug test, moreover, proved to be a minimally invasive and easily
      performed test for evaluating rectal mucosal prolapse.

PMID- 19845270
TI  - [Rectus sheath haematoma as an early complication of laparoscopic hemicolectomy:
      a case report and review of the literature].
AB  - We report a case of rectus sheath haematoma (RSH) in a patient undergoing
      laparoscopic right hemicolectomy and anticoagulant prophylaxis of a pulmonary
      thromboembolism (PTE) with low molecular weight heparin. This pathological
      condition is rare and could be a cause of misdiagnosis in patients with acute
      abdominal pain. It can be a serious complication in the course of anticoagulant
      therapy. A rapid, correct diagnosis may lead to better treatment which must be
      timely, aggressive and ultimately curative. Our patient, with acute onset and
      swift worsening of his general condition, benefited from an immediate surgical
      procedure, with ligature of the epigastric artery stumps and drainage of the
      haematoma.

PMID- 19845271
TI  - [Iatrogenic lesion of the hepatic artery in the course of pancreatic surgery].
AB  - The authors report a case of operative injury of the hepatic artery during a
      total spleno-pancreasectomy procedure for a mixed-type intraductal papillary
      mucinous neoplasm. During the preparation of the structures of the hepatic
      pedicle, a "true" hepatic artery was not identified, but only a small arterial
      vessel measuring about 2 mm in diameter, just in front of the portal vein,
      apparently emerging from the parenchyma of the pancreatic head. To obtain
      complete mobilisation of the duodeno-pancreatic block from the portal vein, it
      was necessary to cut this small arterial vessel. In the postoperative period, the
      patient developed extensive liver ischaemia, which was gradually resolved, but
      resulted in multiple stenosis of the intra- and extra-hepatic biliary tree. At
      follow-up at three years, the patient was in fairly good condition, with a
      permanent percutaneous biliary drainage, but with no clinical or radiological
      signs of local or distant disease. Although interruption of hepatic arterial flow
      is usually well tolerated, this is not always the case. It is important to
      predict in what circumstances complications are likely to occur. The main
      determinants that should guide the surgeon faced with this problem are whether
      the portal circulation is normal, whether structures carrying collateral blood
      supply have been interrupted, and whether some form of biliary reconstruction is
      needed.

PMID- 19845272
TI  - Biliary stent migration into the abdominal wall: a case report.
AB  - Biliary stent migration occurs in about 5% of patients. The most common
      complications secondary to stent migration are pancreatitis, small bowel
      perforation and peritonitis. We report the case of a patient presenting with an
      abdominal wall abscess secondary to migration of a biliary stent. Direct
      abdominal radiography, abdominal ultrasound and CT scan have proved very useful
      in the diagnosis, providing the correct localisation of the stent in the left
      rectus muscle of the abdominal wall that led to a surgical approach under local
      anaesthesia for the removal, and abscess formation surrounding the stent. The
      patient was discharged on the day after surgery. After reviewing the literature
      concerning this rare complication, the Authors conclude that closer monitoring of
      patients with biliary prostheses is needed to prevent the migration and the
      consequent serious complications.

PMID- 19845273
TI  - Cryptogenetic intestinal angiodysplasia and elderly aortic stenosis: Heyde's
      syndrome? A case report.
AB  - Gastrointestinal haemorrhage is extremely frequent, but in some cases the
      aetiology may remain unknown. Haemorrhage from the small bowel especially can
      create important diagnostic problems. We report the case of a patient admitted to
      hospital with intestinal bleeding in an ileal site in association with aortic
      stenosis. Enteric angiodysplasia is a frequent pathology in the surgery of the
      gastrointestinal tract. Recognizing bleeding lesions in the small intestine can
      be really difficult. Concerning the case reported here, the most probable
      diagnostic hypothesis is Heyde's syndrome, which is characterised by valvular
      aortic stenosis together with gastrointestinal bleeding due to cryptogenetic
      angiodysplasias. The choice to be made in the therapeutic management of
      angiodysplasia is still a debatable issue and should be suited to the patient's
      clinical state and the site and extent of the bleeding. In the literature the
      link between aortic valvular stenosis and intestinal angiodysplasia is unclear.
      The physiopathological relationship between the two entities is still mysterious.

PMID- 19845274
TI  - Leiomyosarcoma of the inferior vena cava: a case report and review of the
      literature.
AB  - Leiomyosarcoma of the inferior vena cava is a particularly rare tumour,
      originating from the smooth muscle of the vessel wall. The authors describe the
      case of a female patient admitted with a picture of anorexia and weight loss,
      accompanied by epi- and mesogastric pain. Preoperative examinations revealed the
      presence of a mass of considerable size originating from the inferior vena cava.
      The patient was submitted to surgery consisting in removal of the mass and of
      part of the wall of the vena cava. A review of the literature confirms the rarity
      of this tumour and demonstrates that optimal anatomical knowledge is absolutely
      indispensable for the management of this pathology.

PMID- 19845275
TI  - [Giant angiomyolipoma of the kidney not associated with tuberous sclerosis: a
      case report and review of the literature].
AB  - The authors describe a paradigmatic case of a large renal angiomyolipoma not
      associated with tuberous sclerosis. The lesion was discovered as an incidental
      finding during abdominal ultrasound for other pathology. Owing to the extent of
      the lesion and the appreciable risk of spontaneous rupture and bleeding, we opted
      for surgical treatment. The impossibility of dissecting the angiomyolipoma from
      the right kidney obliged us to perform a nephrectomy. The clinical interest of
      angiomyolipoma is in its rapid growth, the difficulty of distinguishing it from
      malignant lesions, the association with tuberous sclerosis, the presence of
      numerous aspecific symptoms and the difficulty of establishing the correct
      diagnosis and treatment strategy.

PMID- 19845277
TI  - Variations in the superficial palmar arch of the hand.
AB  - Variations in the pattern of the hand blood supply are frequently encountered.
      Awareness and identification of such variations is crucial during hand surgery.
      Thirty formaline fixed hands of male and female cadavers were dissected. All
      arteries contributing to the superficial palmar arch (SPA) of the hand were
      verified. In addition to the frequently encountered types of SPA, three very rare
      cases were described. In the first case, the superficial branch of the radial
      artery passed superficial to the thenar muscles with a diameter larger than that
      of the ulnar artery. In addition to the common palmar digital artery to the
      second web space, it gave the princeps pollicis and radialis indicis arteries. In
      the second case, the SPA was formed by the ulnar artery and was completed by a
      small branch from the deep branch of the radial artery. The palmar digital artery
      to the ulnar side of the fifth finger and the common palmar digital artery to the
      fourth web space arose from a common trunk. In the third case, incomplete SPA was
      formed by the median artery which only gave the princeps pollicis and radialis
      indicis arteries, while the ulnar artery supplied the rest of the hand except the
      ulnar side of the third finger and the second web space which were supplied by
      the deep palmar arch. Therefore, sound knowledge of the pattern of the blood
      supply of the hand by various techniques is crucial to avoid possible
      complications during hand surgery.

PMID- 19845276
TI  - Morphological and microvascular changes of the adrenal glands in streptozotocin
      induced long-term diabetic rats.
AB  - It has been known that diabetes mellitus is associated with hyperfunction of the
      adrenal gland. However, the structural changes of adrenal gland in diabetes have
      rarely been studied. The aims of this study were to investigate the morphological
      and microvascular alterations in streptozotocin (STZ)-induced long-term diabetic
      rats. Twelve male Sprague-Dawley rats were divided into diabetic (n=8) and
      control (n=4) groups. Each diabetic rat was induced by an intraperitoneal
      injection of STZ (60 mg/kg) in citrate buffer (pH 4.5). Control rats were
      intraperitoneally injected with the same amounts of the buffer. These animals
      were sacrificed at 20 weeks after the injections. The adrenal glands were
      processed for the morphological and microvascular studies by using conventional
      light microscopy (LM) and vascular corrosion cast technique combined with
      scanning electron microscopy (SEM), respectively. In the diabetic group, the
      cells in zona glomeruloza (ZG) became atrophied and the thickness of this zone
      was found to be less than that of the controls. In the zona fasciculata (ZF) and
      zona reticularis (ZR), the hypertrophic cells were investigated in both layers.
      The degenerated chromaffin and hypertrophic sympathetic ganglion cells in the
      adrenal medulla were observed. Also some degenerated ganglion cells were found.
      Additionally, lymphocyte infiltration, macrophages and amyloidosis were found in
      the adrenal medulla of long-term diabetic rats with renal failure. Under the SEM
      observation, the luminal diameters of capillaries in the diabetic group were
      dilated in all zones. In addition, these capillaries in the ZF and ZR were
      arranged in tortuous courses. This study demonstrates morphological and
      microvascular changes in the adrenal gland of diabetic rats which are in
      accordance with the hormonal changes reported by previous investigators.

PMID- 19845278
TI  - ANP and insulin presence in human foetal pancreas.
AB  - Aim of this work is to investigate the presence of Atrial natriuretic peptide
      (ANP) and insulin in human foetal pancreas from not diabetic and diabetic
      mothers. The data literature evidenced relationship between serum ANP and
      insulin. The our work carried out on sections immunostained for ANP and insulin
      showed positivity for ANP and insulin in beta-cells of pancreas from diabetic
      mothers, while positivity for insulin in beta-cells of foetuses from not diabetic
      mothers. Results indicate that the insulin presence stimulates the ANP synthesis
      in pancreas of human foetuses from diabetic mothers.

PMID- 19845279
TI  - Comparison of skeletal fibre types between somitic (trunk and limb) and
      presomitic (craniofacial) muscles.

PMID- 19845280
TI  - Ultrastructural features of the gastrointestinal tract in some freshwater teleost
      fish.

PMID- 19845281
TI  - [Steroid furostanol glycosides: a new class of natural adaptogenes (review)].
AB  - The present review summarizes experimental data revealed while studying the
      mechanism of the adaptogenic effect of furostanol glycosides (FG) extracted from
      Dioscorea deltoidea Wall cell culture under the conditions of biotic stress in
      tomato plants Lycopersicon esculenium Mill. induced by the gall nematode
      Meloidogyne incognita Kofoid et White. Comparison of changes in isoprene content
      (phytosterines, tomatin, and carotenoids) and in the rate of oxidative processes
      in the leaves and roots of intact and treated plants evidence that FG cause
      nonspecific defense reactions resulting in the formation of systemic acquired
      resistance. This formation is presented by the enhancement in photosynthetic
      apparatus pigment fund, pigments of the violaxanthin cycle in particular, by
      activation of processes related to POL, and by increase in peroxidase activity
      enzyme of antioxidant protection.

PMID- 19845282
TI  - [Thermoregulation of catalytic activity of enzymes polymeric derivatives].
AB  - Trypsin was immobilized on polymeric carriers with low critical solution
      temperature (LCST). Homopolymer of N,N-diethylacrylamide (DEAA), random
      copolymers of DEAA and acrylamide (AA), and block copolymers polyDEAA-polyAA were
      used as the carriers. It was shown that at a temperature above LCST all carriers
      have a conformation change and trypsin's polymeric derivatives precipitate. The
      maximal activity after phase transition keeps trypsin, immobilized on polyDEAA
      block in polyDEAA-polyAA block-copolymer.

PMID- 19845283
TI  - Immobilization of Alcaligenes faecalis penicillin G acylase on epoxy-type
      supports.
AB  - Alcaligenes faecalis penicillin G acylase has several desired features over other
      penicillin G acylases and its use in industry requires immobilization. In this
      work, two novel supports ZH-EP (epoxy-type) and ZH-HA (epoxy-amino type) were
      used to immobilize Alcaligenes faecalis penicillin G acylase (AfPGA) with
      Eupergit C as reference. The saturation of immobilized protein on ZH-EP (269
      mg/g, 116 h) and ZH-HA (296 mg/g, 15 h) was obtained more rapidly than Eupergit C
      (197 mg/g, 260 h). And the activity of immobilized AfPGA on ZH-EP (520 U/g) and
      ZH-HA (2200 U/g) was higher than that on Eupergit C (310 U/g). The properties of
      three immobilized enzymes were compared and no obvious difference was observed,
      which indicated that ZH-EP and ZH-HA were promised in industry.

PMID- 19845285
TI  - [The mechanism of action of reactivating factor from Luteococcus japonicus subsp.
      casei].
AB  - Reactivating factor (RF) from Luteococcus japonicus subsp. casei was shown to be
      constitutively synthesized and to act a by one-step mechanism, being activated
      independently from stress. Cell reactivation (reversion of a cell's ability to
      form macrocolonies) might be ensured by the membrane mechanism of RF action,
      which is proved with the dependence of antistress activity from the condition of
      the cytoplasmic membrane and with the form of concentration dependence. The
      incubation of UV-treated L. casei suspension with RF increased the number of
      cells with intact barrier membrane (1.6-1.8-fold increase compared to RF
      untreated cells) and the number of colony-forming cells. Cross defensive and
      reactivating RF effects on both L. casei and yeast Saccharomyces cerevisiae cells
      were described. Bacterial and yeast's RF compete for membrane receptors. Matrix
      Assisted Laser Desorption/Ionization time-of-flight (MALDI-TOF) spectrometry
      revealed that RF ofL. casei contained two major peptides of 5.8 and 7.6 kDa,
      while RF of S. cerevisiae was represented by a single peptide of 5.8 kDa. The
      presence of 5.8 kDa peptide in RF from bacteria and yeasts might ensure cross
      responses in these organisms.

PMID- 19845284
TI  - [The study of two alkaliphilic thermophile bacteria of the anoxybacillus genus as
      producers of extracellular proteinase].
AB  - Two strains of alkaliphilic thermophile bacteria of the genus Anoxybacillus from
      hydrothermal vents of Lake Baikal were detected and characterized. It was
      demonstrated that proteinases secreted by these bacteria had wide substrate
      specificity, hydrolyzed proteins and n-nitroanilide substrates, and showed
      maximal activity at pyroglutamyl-alanine-alanine-leucine n-nitroanilide
      hydrolysis. We determined maximal activity of the proteinases at alkaline pH
      values (10.0-10.5), the enzymes were thermostable and were characterized by a
      wide thermal optimum (55-70 degrees C). The results of inhibitor analysis and
      substrate specifity examination of extracellular enzymes demonstrated their
      belonging to the subtilisin-like serine proteinases.

PMID- 19845286
TI  - [Amine neuromediators, their precursors, and oxidation products in the culture of
      Escherichia coli K-12].
AB  - Growth dynamics of the synthesis of monoamine neuromediators serotonin,
      norepinephrine, and dopamine in Escherichia coli K-12 was investigated for the
      first time using high performance liquid chromatography with electrodetection.
      Maximum (micromolar) concentrations of these compounds were detected in E. coli
      cells during the early growth phases; their intracellular content decreases after
      the transition to late growth phases. E. coli biomass contains the substances
      DOPA and 5-hydroxytryptamine that serve in animal cells as neuromediator
      precursors and the products of their oxidative deamination. Presumably, the
      biosynthesis and degradation of monoamine neuromediators in bacterial cells
      involves enzyme systems analogous to those typical of animals. The culture fluid
      of E. coli contains micromolar concentrations of DOPA and nanomolar of serotonin,
      dopamine, and norepinephrine during the late growth phase. These concentrations
      are sufficient for animal/human receptors to bind them. This article deals with
      the potential biotechnological applications of the data obtained.

PMID- 19845287
TI  - [Metabolism characteristics of Chelativorans oligotrophicus by two-phase growth
      on the mixture of EDTA and glucose].
AB  - The obligate destructor of ethylene diamine tetraacetate--a culture of
      Chelativorans oligotrophicus LPM-4--did not grow on a medium with glucose, but it
      was good to use it under cultivation on a mixture with EDTA after considerable
      decrease of the EDTA concentration in the medium (two-phase growth). Strong
      inhibition of hexokinase and glucose 6-phosphate dehydrogenase in cell exracts 4
      mM EDTA was revealed. Using EDTA, cells accumulated polyphosphates whose rate
      decreased during glucose utilization phase. High activities of polyphosphate
      biosynthesis ferments (adenylat kinase and polyphosphate kinase) were
      distinguished during the first phase of the cultivation; considerable decrease of
      them and increase of polyphosphate glucokinase were found during the second phase
      of the cultivation. This points to the possible participating of polyphosphates
      in glucose metabolism as a supplementary energy source.

PMID- 19845288
TI  - [2-(14)C-Methylerythritol 2,4-cyclodiphosphate incorporation into bacterial and
      plant isoprenoids].
AB  - To work out a test system for studying the inhibition of isoprenoid biosynthesis
      through non-mevalonate pathway, the conversion of 2-(14)C-methylerythritol 2,4
      cyclodiphosphate (14C-MEC) into isoprenoids of three bacteria species and into
      plastids of 11 higher plant species was studied. The highest efficiency (up to
      63%) of the process was observed with chromoplasts from narcissus (Narcissus
      pseudonarcissus L.) and celandine (Chelidonium majus L.). Twenty five percent of
      added 14C-MEC was recovered in an isoprenoid fraction of red pepper (Capsicum
      annuum L.) chromoplasts. Thus, these three models can be used to test antibiotic
      inhibitors of isoprenoid biosynthesis.

PMID- 19845289
TI  - [Complex formation between trigliceropeptides pseudomonades and plant root
      exudates as a mechanism of action on phytopathogens].
AB  - The influence of plant exudates on the antifungal activity of Pseudomonas
      chlororaphis strains (BI 6, BI 51) and P. putida (BI 17) was investigated in
      model experiments. Using UV spectroscopy and polarimetry methods,
      triglyceropeptide metabolites from the Pseudomonas strain were shown to form
      intermolecular complexes with plant exudates such as carbohydrates, organic
      acids, and amino acids. The stoichiometric contents of metabolite-exudate
      complexes were evaluated.

PMID- 19845290
TI  - [Synergistic action of entomopathogenic hyphomycetes and the bacteria Bacillus
      thuringiensis ssp. morrisoni in the infection of Colorado potato beetle
      Leptinotarsa decemlineata].
AB  - A synchronous coinfection of the Colorado potato beetle Leptinotarsa decemlineata
      (Say) with the entomopathogenic bacteria Bacillus thuringiensis ssp. morrisoni
      Bonnifoi & de Barjak var. tenebrionis Krieg et al. and hyphomycete Metarhizium
      anisopliae (Metsch.) Sorokin or Beauveria bassiana (Bals.) Vuill leads to the
      rapid death of 95-100% of larvae. The bacteria arrest the nutrition of insects,
      while the fungal spores kill the weakened larvae. The synergistic effect of two
      pathogens is recorded at a relatively low hyphomycete titer (1-5 x 10(6)
      conidia/ml) and is evident in the mortality dynamics at all larval ages. These
      bacterial and fungal pathogens display no antagonism on artificial nutrient
      media. This microbial complex is highly efficient under natural conditions (80
      90% larval mortality rate and no plant defoliation).

PMID- 19845291
TI  - [Parameters of the succinate transport into Saccharomices cerevisiae cells after
      prolonged cold preincubation].
AB  - A nonconventional approach to the measurement of succinate transport through
      plasmalemma is proposed. It is based on the conditions in which the succinate
      oxidation rate is limited by transport through plasmalemma. Impermeable specific
      inhibitor of plasmalemma dicarboxylate transporter was employed as a tool to
      optimize conditions for the transport activity assay. For this purpose yeast
      culture was grown in synthetic medium under selected conditions. After aerobic
      preincubation of S. cerevisiae cells at 0 degree C (instead of incubation at 15
      degrees C), the rate of endogenous respiration decreased substantially and was
      stabilized during measurements at a level that was five times lower than
      oxidation rates in the presence of exogenous substrate. This approach allowed for
      the reproducible determination of K(M) for the dicarboxylate transporter (7.3 +/-
      2.1 mM) within a half-hour period. The advantages and drawbacks of this fast, but
      indirect, assay of slow substrates transport into the cell are compared with
      conventional methods.

PMID- 19845292
TI  - Construction of flocculent industrial yeast by the yeast flocculation gene FLO1.
AB  - The structure gene FLO1 from Saccharomyces cerevisiae W303-1A encoding a
      flocculation protein and the G418 resistance gene kanMX from plasmid pUG6 were
      amplified by PCR method. The expression vector pYX212 harboring FLO1 gene and
      kanMX gene was transformed into Angel yeast. The transformant Angel yeast F6 was
      obtained and showed strong and stable flocculation ability during 20 batches
      inoculation. And the flocculation ability of the transformant Angel yeast F6
      showed no difference in the medium with the initial pH ranging from 3.5 to 6.0.
      Noteworthily, the flocculation onset of the transformant strain was in the early
      stationary growth phase, not coincident with the glucose depletion in the
      cultural medium. And in the experiment the ethanol yield and other properties of
      the transformant Angel yeast F6 were similar to those of the wild-type strain,
      although its fermentation time was a little slower comparing with the wild-type
      strain. Those would be potential application for yeast cells to separate and
      recycle in the fuel ethanol industry.

PMID- 19845293
TI  - Carbon and nitrogen source effects on basidiomycetes exopolysaccharide
      production.
AB  - The capability to synthesize the extracellular polysaccharide (EPS) is widespread
      among eight mushroom species which accumulated 0.6-2.2 g/l of EPS in submerged
      cultivation. Glucose, maltose, and mannitol were the most appropriate carbon
      sources for biomass and EPS production. Organic nitrogen sources appeared to be
      the most suitable nitrogen sources for biomass and EPS accumulation. The
      cultivation process in shake flasks was successfully reproduced in a laboratory
      fermentor with enhanced EPS production. The highest yield of EPS (3.8-4.0 g/l)
      was achieved in cultivation of Agaricus nevoi and Inonotus levis.

PMID- 19845294
TI  - [Water-soluble endopolysaccharides from the fruiting bodies of Laetiporus
      sulphureus (Bull.: Fr.) Murr].
AB  - Endopolysaccharides represented by glucans, galactans, and glycoproteins were
      isolated from the fruiting bodies of the sulfur shelf (Laetiporus sulphureus
      (Bull.:Fr.) Murr), which were obtained by the natural-plantation method. The
      study of the major 56-kDa polysaccharide, laetiporan A, the content of which
      accounted for 0.28% of the fruiting body weight, showed that it is a beta-1,3
      glucan containing mannose, galactose, fucose, xylose, and rhamnose residues at
      position C-6. An antioxidant effect of laetiporan A was discovered.

PMID- 19845295
TI  - [The composition of volatile components of dry cepe and oyster mushroom].
AB  - The composition of aroma compounds in dry cepe mushroom (Boletis edulis Fr.) and
      oyster mushroom (Pleurotus ostreatus Fr.) was studied using capillary gas
      chromatography and chromatography-mass spectrometry. In dry cepe, 53 volatile
      compounds were identified, and in dry oyster mushroom 41 compounds were
      identified. Volatile organic substances with various functional groups formed the
      flavor of dry mushrooms. Unsaturated alcohols and ketones with eight carbon atoms
      were responsible for the mushroom notes of products. Their content in dry cepe
      was much higher than in dry oyster mushroom. The specific aroma of dry cepe was
      formed by the complex mixture of methional, substituted furans, pyrazines, and
      pyrroles. The content of these compounds was higher in dry cepe than in dry
      oyster mushroom. The content of aromatic and aliphatic aldehydes with six, nine,
      and ten carbon atoms was higher in dry oyster mushroom. The differences in the
      qualitative and quantitative composition of volatile compounds are responsible
      for more intensive and pleasant aroma of dry cepe in comparison to that of dry
      oyster mushroom.

PMID- 19845296
TI  - [The impact of melafen on the expression of chloroplastic chaperone protein
      HSP70B and photosynthetic pigments in cells of Chlamydomonas reinhardtii].
AB  - The effects of growth regulator of the new generation-melamine salt of
      bis(oxymethyl)phosphine acid (melafen)--on culture growth, pigment and protein
      content, and the induction of protective chloroplastic chaperone HSP70B in
      Chlamydomonas reinhardtii CW15 cells were studied. Melafen exhibited 10-30%
      growth inhibition at 10(-9)-10(-2)% concentration. At 10(-9)-10(-4)% of melafen
      electrophoretic concentration, the pattern of cellular proteins was similar to
      the control. The alterations in protein content of algae cells were detected only
      at 10(-2)% concentration. The content of chlorophyll and carotenoids in melafen
      treated cells was 17-40% lower than in the control. Melafen at 10(-9)-109-2)%
      concentration inhibited HSP70B induction by 39-43% compared to untreated cells.
      The potential mechanism of melafen effect might involve its influence on nuclear
      gene expression.

PMID- 19845297
TI  - [Stability of the rolC gene and its expression in 15-year-old cell cultures of
      Panax ginseng].
AB  - After 15 years of cultivation of Panax ginseng, transgenic cell cultures were
      shown to express rolC gene at a high level. We determined that the rolC gene
      underwent mutagenesis. In particular, from one to four nucleotides were changed
      for the whole gene sequence (540 bp). These substitutions were synonymous in half
      of the cases or resulted in the modification of single amino acids in the rolC
      encoded protein. With the example of beta-1,3-glucanases we showed that long
      cultivation and the observed changes in nucleotide sequences of the transgene did
      not inhibit the activating effect of rolC on enzymatic activity of beta-1,3
      glucanases.

PMID- 19845298
TI  - Been out of the box lately?

PMID- 19845300
TI  - The "tooth worm" conundrum continues. Micro-images of worm-like structures
      uncovered inside dissected molar.

PMID- 19845299
TI  - Dental sleep medicine: the "new porcelain veneer"?

PMID- 19845301
TI  - Forced eruption by fiber-reinforced composite.

PMID- 19845302
TI  - Treatment options for the edentulous mandible.

PMID- 19845303
TI  - Maximizing aesthetics in the deficient alveolar ridge.
AB  - This article has demonstrated a predictable and aesthetic method for replacing
      the lost bone prior to implant placement through the ramus block graft technique.

PMID- 19845304
TI  - Treating white spots: new caries infiltration technique.
AB  - My patients have appreciated receiving minimally invasive cosmetic enhancement
      without anesthesia, drilling, or more expensive restorations. Because caries
      infiltration prevents lesion progression, it prolongs the life of the tooth and
      provides a "simple" solution for patients who are known for poor compliance.
      Undoubtedly, this innovative material and technique will help many patients avoid
      many more rigorous and invasive restorative procedures.

PMID- 19845305
TI  - Modern endodontic access and dentin conservation, Part I.

PMID- 19845306
TI  - Combining modern materials to create a beautiful smile!

PMID- 19845307
TI  - Creating beautiful smile symmetry: tissue considerations.

PMID- 19845308
TI  - Subcision for lip and perioral scarring cosmesis: case report.

PMID- 19845309
TI  - An elastomeric impression material breakthrough.

PMID- 19845310
TI  - The life-changing power of a healthy mouth and smile.

PMID- 19845312
TI  - Polishing techniques for beauty and longevity.

PMID- 19845311
TI  - New single-arch sleep appliance therapy.

PMID- 19845313
TI  - 2009 fee and insurance code update.

PMID- 19845315
TI  - Effect of polyol on the structure of nonionic surfactant reverse micelles in
      glycerol monoisostearate/decane systems.
AB  - Using small-angle X-ray scattering (SAXS), effects of different polyols used as
      polar additives, glycerol (GC), ethylene glycol (EG), and 1,2-butanediol (1,2
      BD), on the structure of nonionic surfactant glycerol monoisostearate (iso
      C(18)G(1)) reverse micelles in decane have been investigated as a function of
      polyol concentration and temperature. The real space structural functions of the
      reverse micelles were obtained by generalized indirect Fourier transformation
      (GIFT) evaluation of the SAXS data, letting the form factor virtually model-free,
      and the results were complemented by conventional theoretical model fittings. The
      iso-C(18)G(1) forms spheroid type or slightly elongated prolate type micelles in
      n-decane. We have found that addition of these polyols causes two-dimensional (2
      D) growth of the reverse micelles in a similar manner to that induced by added
      water, both the maximum length and micellar cross-section diameter continuously
      increasing with polyol concentration. EG is most effective to increase the
      micellar size. 1,2-BD, which is apparently more hydrophobic than EG, has a
      weakest effect on the micellar growth. Unexpectedly, GC exhibits a less
      pronounced effect than EG despite its stronger hydrophilicity, which may be
      related to the similarity of the molecular structure to the surfactant glycerol
      moiety. The data demonstrate that different polarities of additives can be an
      additional tunable parameter for controlling the structure of the reverse
      micelles. The results well complement our recent findings that slightly different
      properties of solvent oils can provide a significant effect on the reverse
      micellar structures in glycerol-based surfactant systems.

PMID- 19845316
TI  - Particulate templates and ordered liquid bridge networks in evaporative
      lithography.
AB  - We investigate the properties of latex particle templates required to optimize
      the development of ordered liquid bridge networks in evaporative lithography.
      These networks are key precursors in the assembly of solutions of conducting
      nanoparticles into large, optically transparent, and conducting microwire
      networks on substrates (Vakarelski, I. U.; Chan, D. Y. C.; Nonoguchi, T.; Shinto,
      H.; Higashitani, K. Phys. Rev. Lett., 2009, 102, 058303). An appropriate
      combination of heat treatment and oxygen plasma etching of a close-packed latex
      particle monolayer is shown to create open-spaced particle templates which
      facilitates the formation of ordered fully connected liquid bridge networks that
      are critical to the formation of ordered microwire networks. Similar results can
      also be achieved if non-close-packed latex particle templates with square or
      honeycomb geometries are used. The present results have important implications
      for the development of the particulate templates to control the morphology of
      functional microwire networks by evaporative lithography.

PMID- 19845314
TI  - Molecular docking screens using comparative models of proteins.
AB  - Two orders of magnitude more protein sequences can be modeled by comparative
      modeling than have been determined by X-ray crystallography and NMR spectroscopy.
      Investigators have nevertheless been cautious about using comparative models for
      ligand discovery because of concerns about model errors. We suggest how to
      exploit comparative models for molecular screens, based on docking against a wide
      range of crystallographic structures and comparative models with known ligands.
      To account for the variation in the ligand-binding pocket as it binds different
      ligands, we calculate "consensus" enrichment by ranking each library compound by
      its best docking score against all available comparative models and/or modeling
      templates. For the majority of the targets, the consensus enrichment for multiple
      models was better than or comparable to that of the holo and apo X-ray
      structures. Even for single models, the models are significantly more enriching
      than the template structure if the template is paralogous and shares more than
      25% sequence identity with the target.

PMID- 19845317
TI  - Preparation of a stable trifluoroborate salt for the synthesis of 1-aryl-2,2
      difluoro-enolethers and/or 2,2-difluoro-1-aryl-ketones via palladium-mediated
      cross-coupling.
AB  - A bench-stable potassium trifluoroborate enol ether reagent has been prepared.
      This reagent is suitable for the incorporation of 2,2-difluoroenolethers into
      aryl and heteroaryl systems via palladium-mediated cross-coupling with suitable
      halide coupling partners.

PMID- 19845318
TI  - Reaction sequence and kinetics of uranium nitride decomposition.
AB  - The reaction mechanism and kinetics of the thermal decomposition of uranium
      dinitride/uranium sesquinitride to uranium mononitride under inert atmosphere at
      elevated temperature were studied. An increase in the lattice parameter of the
      UN(2)/alpha-U(2)N(3) phase was observed as the reaction temperature increased,
      corresponding to a continuous removal of nitrogen. Electron density calculations
      for these two compounds using XRD powder patterns of the samples utilizing charge
      flipping technique were performed for the first time to visualize the decrease in
      nitrogen level as a function of temperature. Complete decomposition of UN(2) into
      alpha-U(2)N(3) at 675 degrees C and the UN formation after a partial
      decomposition of alpha-U(2)N(3) at 975 degrees C were also identified in this
      study. The activation energy for the decomposition of the UN(2)/alpha-U(2)N(3)
      phase into UN, 423.8 +/- 0.3 kJ/mol (101.3 kcal/mol), was determined under an
      inert argon atmosphere and is reported here experimentally for the first time.

PMID- 19845319
TI  - Self-aggregation behavior of fluorescent carbazole-tailed imidazolium ionic
      liquids in aqueous solutions.
AB  - Three amphiphilic imidazolium ionic liquids (ILs), 1-[n-(N-carbazole)alkyl]-3
      methylimidazolium bromide [carbazoleC(n)mim]Br (n = 6, 10, and 12), that
      incorporate a fluorescent carbazole moiety at the terminal of the hydrocarbon
      chain, were designed and synthesized. Their surface activity, aggregation
      behavior, and thermodynamics of micelle formation in aqueous solutions were
      systematically investigated by surface tension, electrical conductivity, and (1)H
      NMR spectroscopy. The incorporation of bulky carbazole groups led to the loose
      arrangement of [carbazoleC(n)mim]Br molecules at the air-water interface. Both
      the enhanced hydrophobicity and the pi-pi interaction due to the incorporation of
      carbazole groups contributed to the lower critical micelle concentration (cmc)
      and higher micellar aggregation number, reflecting a strong capability of the
      designed carbazole-tailed imidazolium ILs for the formation of micelle. The
      analysis of (1)H NMR spectra revealed that the carbazole moieties may overlap
      with the middle methylenes of the alkyl chains. The amphiphilic carbazole-tailed
      imidazolium ILs demonstrated strong and stable fluorescence properties,
      indicating their potential application in the combined field of surface chemistry
      and photochemistry.

PMID- 19845320
TI  - Tg and rheological properties of triazine-based molecular glasses: incriminating
      evidence against hydrogen bonds.
AB  - Bis(mexylamino)triazines have been identified as a family of compounds showing an
      exceptional propensity to form glassy phases as opposed to crystals. The
      particularities of this family of compounds are their ability to self-assemble
      through hydrogen bonding in well-defined patterns to form supramolecular
      aggregates which pack poorly and the wide range of glass transition temperatures
      (T(g)) that can be attained through minor structural modifications.
      Representative bis(mexylamino)triazines were studied by rheology to establish
      correlations between their rheological properties and their molecular structure,
      and all compounds were found to behave in a similar fashion except for the
      temperature at which glass transition takes place. FTIR and NMR spectroscopy
      experiments were performed on the molecular glasses studied herein; comparisons
      between the viscosity, T(g), hydrogen bonding, and association constant (K(a)) in
      CDCl3 solution have revealed a relationship between the rheological properties,
      the T(g) of the molecular glasses, and the extent and strength of hydrogen
      bonding present in the material.

PMID- 19845321
TI  - Structural basis of pathway-dependent force profiles in stretched DNA.
AB  - Understanding the mechanical properties that determine the flexibility of DNA is
      important, as DNA must bend and/or stretch in order to function biologically.
      Recent single-molecule experiments have shown that above a certain loading rate
      double-stranded DNA is more stable when stretched from the 3' termini than when
      stretched from the 5' termini. Unfortunately these experiments cannot provide
      insight into the structural basis for this behavior. We have used molecular
      dynamics simulations combined with umbrella sampling to study the stability and
      structural changes of a 30 bp double-stranded DNA oligomer during stretching from
      either the 3' termini or the 5' termini. At extensions greater than 1.7x the 3'
      stretched structure is more stable than the 5' stretched structure due to
      retention of twice the number (80%) of native hydrogen bonds between base pairs
      and a higher degree of base stacking. This difference results from greater
      dissipation of the stretch force via conformational flexibility of the phosphate
      backbone when pulled from the 3' ends, whereas in the 5' stretch the force is
      borne more directly by the base pair hydrogen bonds leading to rupture. In
      addition, stretching from the 5' end produces a greater widening of the major
      groove that increases solvent exposure and hydrolysis of the base pair hydrogen
      bonds. These results demonstrate that 3' stretching and 5' stretching in DNA are
      fundamentally different processes.

PMID- 19845322
TI  - Further insights into the environmental effects on the computed hyperfine
      coupling constants of nitroxides in aqueous solution.
AB  - We investigated the main two factors influencing the mean hyperfine coupling
      constants of small nitroxide radicals in aqueous solution, i.e., the out-of-plane
      displacement of their nitrogen atom and the environmental effects (solvent
      effects), by means of the approach we previously developed and fine-tuned to
      study the solvation of the dimethyl nitroxide radical. Our methodology
      efficiently combines classical molecular dynamics based on a polarizable force
      field at the nanosecond scale and quantum mechanics/molecular mechanics (QM/MM)
      computations to account for the bulk instantaneous electrostatic environmental
      effect. Our method has been applied to five small nitroxides, namely methyl
      nitroxide, ethyl nitroxide, dimethyl nitroxide, di-tert-butyl nitroxide, and
      PROXYL. The theoretical nitrogen hyperfine coupling constant values for the five
      nitroxides in solution are in good agreement with experiment (difference of 0.3 G
      on average). Our approach showed that the solvent shift in nitroxide hyperfine
      coupling constants is almost constant whatever the nitroxide, and, particularly,
      whatever the nitroxide NO moiety's accessibility to the solvent. This result
      contrasts with earlier results derived from 10 ps scale trajectories based on Car
      Parrinello molecular dynamics approach. However, we show that if we consider on
      average these latter results, they are in agreement with our conclusion. We also
      present an attempt to identify the origin of this result by analyzing the solvent
      contributions in terms of effects of the nitroxide first hydration shell and of
      the bulk, and by investigating the relation between these two contributions and
      the solvent structure at the vicinity of the NO moiety.

PMID- 19845323
TI  - Spectroelectrochemical study of the [NiFe] hydrogenase from Desulfovibrio
      vulgaris Miyazaki F in solution and immobilized on biocompatible gold surfaces.
AB  - The catalytic cycle of the anaerobic [NiFe] hydrogenase from Desulfovibrio
      vulgaris Miyazaki F (DvMF) both in solution and immobilized on an Au electrode
      was studied by IR spectroscopic and electrochemical methods. IR
      spectroelectrochemistry in solution at different pH values allows the
      identification of the various redox-states of the active site and the
      determination of the midpoint potentials, as well as their acid-base equilibria.
      The spectroscopic characterization was based on the unique marker bands of the CN
      and CO stretching modes of the Ni-Fe center and served as reference for the
      surface-enhanced IR absorption (SEIRA) study of the immobilized enzyme. Using
      structural models of hydrogenases from DvMF and Desulfovibrio gigas , dipole
      moment calculations were carried out to guide the immobilization strategy. In
      view of the high dipole moment of about 1100 D pointing through the negatively
      charged area surrounding the distal [FeS] cluster, the Au electrode was coated by
      a self-assembled monolayer of amino-terminated mercaptanes which, due to the
      positively charged head groups, permit a durable electrostatic binding of the
      protein. SEIRA spectroscopy revealed a structurally and functionally intact
      active site as demonstrated by the reversible activation and inactivation under
      hydrogen and argon, respectively. Cyclic voltammetry on the immobilized enzyme
      demonstrate a reversible anaerobic inactivation upon changing the applied
      potential. The "switch" potential (E(switch)) associated with the reductive
      reactivation was determined to be -33 mV (vs normal hydrogen electrode). However,
      the catalytic current decreased on the time scale of hours during continuous
      cycling. SEIRA experiments demonstrate that the loss of catalytic activity is not
      due to protein desorption but is rather related to a slow degradation of the
      active site, possibly initiated by the attack of reactive species
      electrochemically generated from residual traces of oxygen in solution.

PMID- 19845324
TI  - Interpretation of light scattering and turbidity measurements in aggregated
      systems: effect of intra-cluster multiple-light scattering.
AB  - In this work we studied the effect of intracluster multiple-light scattering on
      the scattering properties of a population of fractal aggregates. To do so,
      experimental data of diffusion-limited aggregation for three polystyrene latexes
      with similar surface properties but different primary particle diameters (equal
      to 118, 420, and 810 nm) were obtained by static light scattering and by means of
      a spectrophotometer. In parallel, a population balance equation (PBE) model,
      which takes into account the effect of intracluster multiple-light scattering by
      solving the T-matrix and the mean-field version of T-matrix, was formulated and
      validated against time evolution of the root mean radius of gyration, <R(g)>, of
      the zero angle intensity of scattered light, I(0), and of the turbidity, tau. It
      was found that the mean-field version of the T-matrix theory is able to correctly
      predict the time evolution of all measured light scattering quantities for all
      sizes of primary particles without any adjustable parameter. The structure of the
      aggregates, characterized by fractal dimension, d(f), was independent of the
      primary particle size and equal to 1.7, which is in agreement with values found
      in literature. Since the mean-field version of the T-matrix theory used is rather
      complicated and requires advanced knowledge of cluster structure (i.e., the
      particle-particle correlation function), a simplified version of the light
      scattering model was proposed and tested. It was found that within the range of
      operating conditions investigated, the simplified version of the light scattering
      model was able to describe with reasonable accuracy the time evolution of all
      measured light scattering quantities of the cluster mass distribution (CMD) for
      all three sizes of primary particles and two values of the laser wavelength.

PMID- 19845325
TI  - Oxygen adsorption on beta-cristobalite polymorph: ab initio modeling and
      semiclassical time-dependent dynamics.
AB  - The adsorption dynamics of atomic oxygen on a model beta-cristobalite silica
      surface has been studied by combining ab initio electronic structure calculations
      with a molecular dynamics semiclassical approach. We have evaluated the
      interaction potential of atomic and molecular oxygen interacting with an active
      Si site of a model beta-cristobalite surface by performing DFT electronic
      structure calculations. As expected, O is strongly chemisorbed, E(b) = 5.57 eV,
      whereas molecular oxygen can be weakly adsorbed with a high-energy barrier to the
      adsorption state of approximately 2 eV. The binding energies calculated for
      silica clusters of different sizes have revealed the local nature of the O,O(2)
      silica interaction. Semiclassical collision dynamic calculations show that O is
      mainly adsorbed in single-bounce collisions, with a smaller probability for
      adsorption via a multicollision mechanism. The probability for
      adsorption/desorption (reflected) collisions at the three impact energies is
      small but not negligible at the higher energy considered in the trajectory
      calculations, about P(r) = 0.2 at E(kin) = 0.8 eV. The calculations give evidence
      of a complex multiphonon excitation-deexcitation mechanism underlying the
      dynamics of stable adsorption and inelastic reflection collisions.

PMID- 19845326
TI  - An efficient method for the preparation of oxo molybdenum salalen complexes and
      their unusual use as hydrosilylation catalysts.
AB  - A number of molybdenum(VI) dioxo salalen complexes were prepared from the
      reaction of Mo(CO)(6) and salen ligands containing bulky substituents, providing
      a novel and facile entry to Mo-salalen compounds. Two of the complexes were
      characterized by single-crystal X-ray diffraction. Reduction with organic
      phosphines or silanes afforded the monooxo molybdenum(IV) complexes, along with
      dinuclear molybdenum(V) species featuring a bridged oxo ligand (mu-O). One of the
      dinuclear complexes as well as a molybdenum(VI) dioxo salan complex was
      characterized structurally. All of the molybdenum compounds except the monooxo
      molybdenum(IV) were fully characterized by NMR, mass spectrometry, and elemental
      analyses. Investigations of acetophenone and 4-Ph-2-butanone reduction with
      PhSiH(3) showed that all of these molybdenum oxo complexes could serve as
      catalysts at reasonably low loading (1 mol % Mo) and approximately 110 degrees C.
      The time profiles and efficacy of catalysis varied depending on the precursor
      form of the catalyst, Mo(VI)(O)(2) vs (O)Mo(V)-O-Mo(V)(O) vs Mo(IV)(O). Solvent
      effects, radical scavenger probes, and other mechanistic considerations reveal
      that the monooxo molybdenum(IV) is the most likely active form of the catalyst.

PMID- 19845327
TI  - Water in the half shell: structure of water, focusing on angular structure and
      solvation.
AB  - Water is a highly polar molecule, consisting of a very electronegative atom,
      oxygen, bonded to two weakly electropositive hydrogen atoms with two lone pairs
      of electrons. These features give water remarkable physical properties, some of
      which are anomalous, such as its lower density in the solid phase compared with
      the liquid phase. Its ability to serve as both a hydrogen bond donor and hydrogen
      bond acceptor governs its role as a solvent, a role that is of central interest
      for biological chemists. In this Account, we focus on water's properties as a
      solvent. Water dissolves a vast range of solutes with solubilities that range
      over 10 orders of magnitude. Differences in solubility define the fundamental
      dichotomy between polar, or hydrophilic, solutes and apolar, or hydrophobic,
      solutes. This important distinction plays a large part in the structure,
      stability, and function of biological macromolecules. The strength of hydrogen
      bonding depends on the H-O...O H-bond angle, and the angular distribution is
      bimodal. Changes in the width and frequency of infrared spectral lines and in the
      heat capacity of the solution provide a measure of the changes in the strength
      and distribution of angles of the hydrogen bonds. Polar solutes and inorganic
      ions increase the population of bent hydrogen bonds at the expense of the more
      linear population, while apolar solutes or groups have the opposite effect. We
      examine how protein denaturants might alter the solvation behavior of water. Urea
      has very little effect on water's hydrogen bond network, while guanidinium ions
      promote more linear hydrogen bonds. These results point to fundamental
      differences in the protein denaturation mechanisms of these molecules. We also
      suggest a mechanism of action for antifreeze (or thermal hysteresis) proteins:
      ordering of water around the surface of these proteins prior to freezing appears
      to interfere with ice formation.

PMID- 19845328
TI  - Intermetallic communication in titanium(IV) ferrocenyldiketonates.
AB  - A tetradentate bis(ferrocenyldiketonate) ligand, Fc(2)BobH(2), is prepared via
      Claisen condensation of acetylferrocene and 2,2'-biphenyldiacetyl chloride, and
      is metalated with titanium(IV) isopropoxide to give (Fc(2)Bob)Ti(O(i)Pr)(2) in
      good yield. The isopropoxide groups are replaced with di(4-nitrophenyl)phosphate
      groups on treatment with the corresponding acid, and with chlorides on treatment
      with trimethylsilyl chloride. Metathesis with catechol leads to the bis(o
      hydroxyphenoxide) complex rather than the chelating catecholate complex.
      Hydrolysis selectively gives the mu-oxo trimer
      (Delta,Delta,Delta)/(Lambda,Lambda,Lambda)-{(Fc(2)Bob)Ti(mu-O)}(3). The solid
      state structures of the mu-oxo trimer and the bis(o-hydroxyphenoxide) complex
      show that the ferrocene substituents are oriented proximal to the biphenyl
      backbone rather than pointed out toward the exogenous groups. The complexes show
      dramatic changes in color depending on the bound anions, ranging from the red
      isopropoxide (lambda(max) = 489 nm) to the green bis(di(4-nitrophenyl)phosphate)
      (lambda(max) = 653 nm). The oxidation potentials of the ferrocenes show modest
      shifts based on the titanium environment, but the redox potentials of the two
      ferrocenes are never separated by more than 60 mV. These results and those of
      density-functional theory (DFT) calculations indicate that the titanium interacts
      principally with the lowest unoccupied molecular orbital (LUMO) of the
      ferrocenyldiketonate and very little with its highest occupied molecular orbital
      (HOMO).

PMID- 19845329
TI  - A multiconfigurational ab initio study of the zero-field splitting in the di- and
      trivalent hexaquo-chromium complexes.
AB  - A detailed analysis of the value of zero-field splitting for the di- and
      trivalent chromium hexaquo complexes is presented. The effect of the Jahn-Teller
      distortion was studied, for the case of the divalent complex, through the use of
      state-averaged CASSCF calculations, for the mapping of the potential energy
      surface along the e(g) normal modes. At the minima of the surface,
      multiconfigurational ab initio calculations (spectroscopy oriented configuration
      interaction, SORCI, and difference dedicated configuration interaction, DDCI)
      were used for the calculation of the D tensor and the analysis of the individual
      contributions to it. The final value calculated with the SORCI method (D = -2.45
      cm(-1)) for the divalent complex is in excellent agreement with the experimental
      estimate (D = -2.3 cm(-1)). The importance of inclusion of the direct spin-spin
      coupling contribution to D is pointed out ( approximately 16%). At the same time,
      contributions of the higher than the lowest (3)T(1g) triplets were found to be
      non-negligible as well ( approximately 11%). The accuracy of second-order
      perturbation theory for the calculation of SOC was investigated and found to be
      satisfactory. For comparison, DFT calculations were performed with hybrid (B3LYP)
      and nonhybrid (BP86) functionals and were found to be inferior to the wave
      function based ab initio methods.

PMID- 19845330
TI  - Transfer of large-area graphene films for high-performance transparent conductive
      electrodes.
AB  - Graphene, a two-dimensional monolayer of sp(2)-bonded carbon atoms, has been
      attracting great interest due to its unique transport properties. One of the
      promising applications of graphene is as a transparent conductive electrode owing
      to its high optical transmittance and conductivity. In this paper, we report on
      an improved transfer process of large-area graphene grown on Cu foils by chemical
      vapor deposition. The transferred graphene films have high electrical
      conductivity and high optical transmittance that make them suitable for
      transparent conductive electrode applications. The improved transfer processes
      will also be of great value for the fabrication of electronic devices such as
      field effect transistor and bilayer pseudospin field effect transistor devices.

PMID- 19845331
TI  - Screening in nanowires and nanocontacts: field emission, adhesion force, and
      contact resistance.
AB  - The explanations of several nanoscale phenomena such as the field enhancement
      factor in field emission, the large decay length of the adhesion force between a
      metallic tip and a surface, and the contact resistance in a nanowire break
      junction have been elusive. Here we develop an analytical theory of Thomas-Fermi
      screening in nanoscale structures. We demonstrate that nanoscale dimensions give
      rise to an effective screening length that depends on the geometry and physical
      boundary conditions. The above phenomena are shown to be manifestations of the
      effective screening length.

PMID- 19845332
TI  - 2-Phenoxypyridyl dinucleating ligands for assembly of diiron(II) complexes:
      efficient reactivity with O(2) to form (mu-Oxo)diiron(III) units.
AB  - A series of 2-phenoxypyridyl and 2-phenoxyimino ligands, H(2)L(R,R') [2,2'-(5,5'
      (1,2-phenylenebis(ethyne-2,1-diyl))bis(pyridine-5,2-diyl))diphenol, where R = H,
      Me, or t-Bu, and R' = H or Ph] and H(2)BIPS(Me,Ph) [(3,3'-(1E,1'E)-(3,3'
      sulfonylbis(3,1-phenylene)bis(azan-1-yl-1-ylidene))bis(methan-1-yl-1
      ylidene)bis(5-methylbiphenyl-2-ol)], were synthesized as platforms for nonheme
      diiron(II) protein model complexes. UV-vis spectrophotometric studies and
      preparative-scale reactions of L(R,R') or BIPS(Me,Ph), where L(R,R') and
      BIPS(Me,Ph) are the deprotonated forms of H(2)L(R,R') and H(2)BIPS(Me,Ph),
      respectively, with iron(II) revealed that the presence of sterically protective o
      phenol substituents is necessary to obtain discrete dinuclear species. The
      reaction of L(Me,Ph) with iron(II) in tetrahydrofuran (THF) afforded the doubly
      bridged compound [Fe(2)(L(Me,Ph))(2)(THF)(3)] (1), which was characterized in the
      solid state by X-ray crystallography. A large internal cavity in this complex
      facilitates its rapid reaction with dioxygen, even at -50 degrees C, to produce
      the thermodynamically stable [Fe(2)(mu-O)(L(Me,Ph))(2)] (2) species. Reaction of
      (18)O(2) instead of (16)O(2) with 1 led to a shift in the Fe-O-Fe vibrational
      frequency from 833 to 798 cm(-1), confirming the presence of the (mu
      oxo)diiron(III) core and molecular oxygen as the source of the bridging oxo
      group. The L(Me,Ph) ligand is robust toward oxidative decomposition and does not
      display any reversible redox activity.

PMID- 19845333
TI  - Multimodal, nanoscale, hyperspectral imaging demonstrated on heterostructures of
      quantum dots and DNA-wrapped single-wall carbon nanotubes.
AB  - A multimodality imaging technique integrating atomic force, polarized Raman, and
      fluorescence lifetime microscopies, together with 2D autocorrelation image
      analysis is applied to the study of a mesoscopic heterostructure of nanoscale
      materials. This approach enables simultaneous measurement of fluorescence
      emission and Raman shifts from a quantum dot (QD)-single-wall carbon nanotube
      (SWCNT) complex. Nanoscale physical and optoelectronic characteristics are
      observed including local QD concentrations, orientation-dependent polarization
      anisotropy of the SWCNT Raman intensities, and charge transfer from photoexcited
      QDs to covalently conjugated SWCNTs. Our measurement approach bridges the
      properties observed in bulk and single nanotube studies. This methodology
      provides fundamental understanding of the charge and energy transfer between
      nanoscale materials in an assembly.

PMID- 19845334
TI  - Quantification of membrane proteins using nonspecific protease digestions.
AB  - We present a mass spectrometry-based method for the identification and
      quantification of membrane proteins using the low-specificity protease Proteinase
      K, at very high pH, to digest proteins isolated by a modified SDS-PAGE protocol.
      The resulting peptides are modified with a fragmentation-directing isotope
      labeled tag. We apply the method to quantify differences in membrane protein
      expression of Bacillus subtilis grown in the presence or absence of glucose.

PMID- 19845335
TI  - CoS supersedes Pt as efficient electrocatalyst for triiodide reduction in dye
      sensitized solar cells.
AB  - We report an efficient nonplatinized flexible counter electrode for dye
      sensitized solar cells. In combination with a solvent-free ionic liquid
      electrolyte, we have demonstrated a approximately 6.5% cell with an amphiphilic
      ruthenium polypyridyl photosensitizer showing excellent stability measured under
      prolonged light soaking at 60 degrees C. Compared to the Pt deposited PEN film,
      the CoS deposited PEN film shows higher electrocatalytic activity for the
      reduction of triiodide. This is expected to have an important practical
      consequence on the production of flexible low-cost and lightweight thin film DSC
      devices based on the plastic matrix.

PMID- 19845336
TI  - Energy minimization of single-walled titanium oxide nanotubes.
AB  - Different crystal structures have been proposed as a basis for titanium oxide
      nanotubes. We have used atomistic simulation techniques to calculate the relative
      stability of nanotubes with these different crystal structures. Our approach is
      to use energy minimization, where the total interaction energy is calculated with
      interatomic potentials based on the Born model of solids. The results reveal
      nanotubes with the trititanate structure to be the most stable (at unit activity
      for water). Indeed, nanotubes with the trititanate structure were found to be
      thermodynamically more favorable than bulk trititanate for nanotube diameters
      greater than approximately 8 nm. However, the formation of cross-linking bonds
      between layers of the trititanate structure occurred frequently; this problem was
      eliminated by replacing two out of three Ti(4+) ions with Ti(3+) ions, although
      this resulted in a higher energy. Of the structures that do not contain hydrogen,
      chiral nanotubes made from (101) sheets of anatase are the lowest in energy,
      suggesting that this is the most likely structure for nanotubes synthesized at
      low water chemical potential. In general, the stability of the nanotubes
      increased as the nanotube diameter increased.

PMID- 19845337
TI  - Almost perfectly symmetric SWCNT-based CMOS devices and scaling.
AB  - Symmetric n- and p-type field-effect transistors (FETs) have been fabricated on
      the same undoped single-walled carbon nanotube (SWCNT). The polarity of the FET
      is defined by controlled injection of electrons (n-type, via Sc electrodes) or
      holes (p-type, via Pd electrodes) into the SWCNT, instead of via chemically
      doping the SWCNT. The SWCNT-based FETs with different channel lengths show a
      clear trend of performance improvement for channel length scaling. Taking full
      advantage of the perfect symmetric band structure of the semiconductor SWCNT, a
      perfect SWCNT-based CMOS inverter is demonstrated, which gives a voltage gain of
      over 160, and for the two adjacent n- and p-type FETs fabricated on the same
      SWCNT, high field mobility is realized simultaneously for electrons (3000
      cm(2)/V.s) and holes (3300 cm(2)/V.s).

PMID- 19845338
TI  - Lipophilic 2,5-disubstituted pyrroles from the marine sponge Mycale sp. inhibit
      mitochondrial respiration and HIF-1 activation.
AB  - The lipid extract of the marine sponge Mycale sp. inhibited the activation of
      hypoxia-inducible factor-1 (HIF-1) in a human breast tumor T47D cell-based
      reporter assay. Bioassay-guided isolation and structure elucidation yielded 18
      new lipophilic 2,5-disubstituted pyrroles and eight structurally related known
      compounds. The active compounds inhibited hypoxia-induced HIF activation with
      moderate potency (IC50 values <10 microM). Mechanistic studies revealed that the
      active compounds suppressed mitochondrial respiration by blocking NADH-ubiquinone
      oxidoreductase (complex I) at concentrations that inhibited HIF-1 activation.
      Under hypoxic conditions, reactive oxygen species produced by mitochondrial
      complex III are believed to act as a signal of cellular hypoxia that leads to HIF
      1alpha protein induction and activation. By inhibiting electron transport (or
      delivery) to complex III under hypoxic conditions, lipophilic Mycale pyrroles
      appear to disrupt mitochondrial ROS-regulated HIF-1 signaling.

PMID- 19845339
TI  - Formation of PbS nanowire pine trees driven by screw dislocations.
AB  - The basic characteristics of nanowire growth driven by screw dislocations were
      investigated by synthesizing hierarchical lead sulfide (PbS) nanowire "pine
      trees" using chemical vapor deposition of PbCl(2) and S precursors and
      systematically observing the effects of various growth parameters, such as
      hydrogen flow, temperature, pressure, and the growth substrates employed.
      Statistical surveys showed that the growth rate of the dislocation-driven trunk
      is about 6 mum/min and that of the vapor-liquid-solid (VLS) driven branch
      nanowire is about 1.2 mum/min under the typical reaction conditions at 600
      degrees C, 900 Torr, and a hydrogen flow rate of 1.5 sccm. The onset of hydrogen
      flow plus the presence of fresh silicon have been identified as the critical
      ingredients for generating PbS nanowire trees reproducibly. To explain the
      experimental findings in the context of classical crystal growth theory, the
      former is suggested to create a spike in supersaturation of the actual sulfur
      precursor H(2)S and initiate dislocations with screw components that then
      propagate anisotropically to form the PbS nanowire trunks. Maintaining suitable
      hydrogen flow provides a favorable low supersaturation that promotes dislocation
      driven trunk nanowire growth and enables the simultaneous VLS nanowire growth of
      branches. Furthermore, thermodynamic consideration and experiments showed that
      silicon fortuitously controls the supersaturation by reversibly reacting with
      H(2)S to form SiS(2) and that SiS(2) can also be a viable precursor for PbS
      nanowire growth. The key requirements of screw dislocation-driven nanowire growth
      are summarized. This study provides some general guidelines for further nanowire
      growth driven by screw dislocations.

PMID- 19845340
TI  - Apple (Malus domestica L. Borkh.) allergen Mal d 1: effect of cultivar,
      cultivation system, and storage conditions.
AB  - It has been reported on the basis of skin prick tests and gene expression studies
      that apple cultivars differ in their allergenic potential. Only a few studies
      have tried to measure the amount of the major apple allergen Mal d 1 so far. Mal
      d 1 belongs to the pathogenesis-related proteins, a family of proteins that are
      induced by pathogens and environmental stress. Due to cross-reactivity between
      Bet v 1 and proteins present in several plant-derived foods, birch pollen
      allergic patients develop food allergies, most frequently to apples. Mal d 1
      content was quantified in different apple cultivars, cultivated at the research
      stations Klein-Altendorf and Bavendorf, dependent on cultivation method and
      storage conditions by sandwich-ELISA. Apple cultivars differ considerably in
      their Mal d 1 content. A high variability in Mal d 1 content was determined
      within one cultivar and between the two locations for the same apple cultivar. In
      most cases organically cultivated fruit showed lower Mal d 1 content in
      comparison to fruit from integrated production. At harvest the detected
      concentration of Mal d 1 was low, but during storage the Mal d 1 content
      increased significantly.

PMID- 19845341
TI  - Various modes of void closure during dry sintering of close-packed nanoparticles.
AB  - Film formation from aqueous suspensions of polymer nanoparticles is an important
      process in many environmental friendly applications and particularly for
      waterborne coatings. This process occurs via three mains steps: concentration,
      sintering, and interdiffusion. During the sintering step, the particles in close
      packed morphology deform and the interstices between them close under Laplace
      pressure. This step is crucial in the film formation process since it is where
      the suspension turns into a uniform defect-free film. Most of the experimental
      and theoretical studies on sintering assume that the interstices close uniformly
      over the entire film. We use small-angle neutron scattering to probe void closure
      between polystyrene nanoparticles. We show that the voids close simultaneously
      and uniformly throughout the annealing process in large particles. For particles
      with a diameter smaller than 60 nm, we interpret the results to show that the
      interstices close heterogeneously at the nanoscopic level: in the beginning of
      annealing, some interstices close while others enlarge, and eventually they all
      vanish. The difference between the behavior of large and small particles is
      related to the high polydispersity of small particles compared to the larger
      ones.

PMID- 19845342
TI  - Imbibition in porous membranes of complex shape: quasi-stationary flow in thin
      rectangular segments.
AB  - The sustained liquid flow of a typical lateral flow assay can be mimicked by two
      dimensional shaped, thin porous membranes, specifically rectangular membranes
      appended to circular sectors. In designing these fan-shaped devices, we have been
      aided by analytical equations and finite-element simulations. We show both
      mathematically and experimentally how a continuous increase in unwetted pore
      volume causes a deviation from traditional imbibition, and leads to quasi
      stationary flow in the rectangular element. These results are both theoretically
      and practically important because they indicate how medical diagnostic test
      strips may be fabricated without incorporating an absorbent pad.

PMID- 19845343
TI  - Monodisperse cell-encapsulating peptide microgel beads for 3D cell culture.
AB  - This paper describes a method to produce monodisperse cell-encapsulating microgel
      beads composed of a self-assembling peptide gel for three-dimensional (3D) cell
      culture. We used a 3D microfluidic axisymmetric flow-focusing device with an
      external gelation method. The finely powdered salts were dispersed into a
      continuous phase, and the salts induced the gelation when in contact with the
      peptide solution. Over 93% of the cells survived after the encapsulation, and the
      cells migrated and grew within the gels. Applications of our cell-encapsulating
      beads include bead-based cell assays in drug testing and engineering tissue
      constructs.

PMID- 19845344
TI  - Dual labeling of metabolites for metabolome analysis (DLEMMA): A new approach for
      the identification and relative quantification of metabolites by means of dual
      isotope labeling and liquid chromatography-mass spectrometry.
AB  - Advanced metabolomics technologies are anticipated to permit the identification
      and quantification of metabolites at the whole-metabolome scale. Yet, most of the
      metabolites either remain unknown or cannot be identified unambiguously.
      Moreover, the present approaches suffer from inaccuracies in relative
      quantification because of sample preparation and matrix effects. Here we present
      Dual Labeling of Metabolites for Metabolome Analysis (DLEMMA) as a valuable tool,
      which with analogy to DNA array assays enables the identification and relative
      quantification of differential metabolites in a single sample. DLEMMA was
      demonstrated as an efficient method for reducing the number of possible chemical
      structures assigned that exhibit the same elemental composition. Its strength was
      exemplified by the discovery of 10 novel Tryptophan derivatives. Furthermore,
      employing DLEMMA by feeding two Phenylalanine-labeled precursors, we could detect
      differential metabolites between transgenic and control plants. The accuracy of
      relative quantification is also enhanced since DLEMMA provides identical matrixes
      for both samples, thus avoiding the effects of different complex biological
      matrixes on electrospray ionization. Hence, DLEMMA will complement and contribute
      to the advancement of metabolomics technologies and boost metabolic pathway
      discovery in diverse organisms.

PMID- 19845345
TI  - Analysis of phosphorylated peptides by double pseudoneutral loss extraction
      coupled with derivatization using N-(4-bromobenzoyl)aminoethanethiol.
AB  - The analysis of post-translational phosphorylation is a crucial step in
      understanding the mechanisms of many physiological events. Numerous approaches
      for the development of analytical methods aimed at the detection and
      quantification of phosphorylated proteins by mass spectrometry have been reported
      in the literature. In this paper, we report a new strategy for the identification
      of phosphorylated serine and threonine residues in phosphoproteins. This method
      consists of selective derivatization of phosphoproteins coupled with double
      pseudoneutral loss extraction after nanoLC/ESI-MS/MS analysis. First, we designed
      and synthesized a new derivatization reagent, N-(4-bromobenzoyl)aminoethanethiol,
      which can selectively react with alpha,beta-unsaturated ketones produced by beta
      elimination of a phosphoryl group from phosphorylated serine or threonine
      residues. The mass spectrum of the derivatized peptide shows a product ion with a
      characteristic isotopic pattern. After derivatization, fragment ions of peptides
      with phosphoserine or phosphothreonine have twin peaks with an intensity ratio of
      approximately 1:1 and a difference of two mass units, while product ions from
      peptides without phosphoserine or phosphothreonine have normal isotopic patterns.
      Therefore, the neutral loss of the derivatized residue in the product ion mass
      spectrum includes two difference losses caused by (79)Br and (81)Br. The
      extraction of the product scan mass spectrum with double pseudoneutral losses is
      very effective for identification of the derivatized peptides produced from
      phosphorylated peptides. The new strategy represents a useful tool for the
      analysis of phosphorylated serine and threonine residues in phosphorylated
      proteins.

PMID- 19845346
TI  - Dynamics of wetting revisited.
AB  - We present new spreading-drop data obtained over four orders of time and apply
      our new analysis tool G-Dyna to demonstrate the specific range over which the
      various models of dynamic wetting would seem to apply for our experimental
      system. We follow the contact angle and radius dynamics of four liquids on the
      smooth silica surface of silicon wafers or PET from the first milliseconds to
      several seconds. Analysis of the images allows us to make several hundred contact
      angle and droplet radius measurements with great accuracy. The G-Dyna software is
      then used to fit the data to the relevant theory (hydrodynamic, molecular-kinetic
      theory, Petrov and De Ruijter combined models, and Shikhmurzaev's formula). The
      distributions, correlations, and average values of the free parameters are
      analyzed and it is shown that for the systems studied even with very good data
      and a robust fitting procedure, it may be difficult to make reliable claims as to
      the model which best describes results for a given system. This conclusions also
      suggests that claims based on smaller data sets and less stringent fitting
      procedures should be treated with caution.

PMID- 19845347
TI  - Effect of temperature on high shear-induced gelation of charge-stabilized
      colloids without adding electrolytes.
AB  - We demonstrated previously (Wu, H.; Zaccone, A.; Tsoutsoura, A.; Lattuada, M.;
      Morbidelli, M. Langmuir 2009, 25, 4715) that, for a colloid stabilized by charges
      from both polymer chain-end groups and adsorbed sulfonate surfactants, when the
      surfactant surface density reaches a certain critical value, the shear-induced
      gelation becomes unachievable at room temperature, even at an extremely large
      Peclet number, Pe = 4.6 x 10(4). This is due to the presence of the short-range,
      repulsive hydration force generated by the adsorbed surfactant. In this work, we
      investigate how such hydration force affects the shear-induced gelation at higher
      temperatures, in the range between 303 and 338 K. It is found that a colloidal
      system, which does not gel at room temperature in a microchannel at a fixed Pe =
      3.7 x 10(4), does gel when temperature increases to a certain value. The critical
      initial particle volume fraction for the gelation to occur decreases as
      temperature increases. These results indicate that the effect of the hydration
      force on the gelation decreases as temperature increases. Moreover, we have
      observed that at the criticality only part of the primary particles is converted
      to the gel network and the effective particle volume fraction forming the gel
      network does not change significantly with temperature. The effective particle
      volume fraction is also independent of the surfactant surface coverage. Since the
      effective particle volume fraction corresponds to space filling requirement of a
      standing gel network, which is mainly related to the clusters structure, this
      result indicates that at a given shear rate the cluster structure does not change
      significantly with the surfactant surface coverage. On the other hand, since the
      cluster morphology is a strong function of the shear rate, we have observed that
      when the Peclet number is lowered from Pe = 3.7 x 10(4) to 1.7 x 10(4), the
      effective particle volume fraction reduces from 0.19 to 0.12 at 313 K.

PMID- 19845348
TI  - Degradation of anthocyanins and anthocyanidins in blueberry jams/stuffed fish.
AB  - This study examined the effects of cooking on the degradation of anthocyanins and
      anthocyanidins of blueberries (Vaccinium corymbosum L.) from cultivar Bluecrop.
      Fruits were used to prepare jams with different degrees Brix and stuffed fish. A
      systematic evaluation of the degradation of anthocyanins and anthocyanidins of
      blueberries was performed; for that purpose an HPLC/DAD method was used to
      determine anthocyanin profile and anthocyanidin contents in fresh and cooked
      blueberries and in jams. Ten anthocyanins were separated and monitored in
      methanolic extracts. Of the six common anthocyanidins, four were identified in
      the hydrolysates, namely, delphinidin, cyanidin, petunidin and malvidin.
      Percentage of degradation of anthocyanins and anthocyanidins in jams is highly
      dependent on degrees Brix: 64-76 degrees Brix led to 20-30% degradation, whereas
      80 degrees Brix resulted in degradation between 50 and 60%. Percentage of
      degradation of anthocyanins in whole blueberries cooked in stuffed fish ranged
      between 45 and 50%, however, for anthocyanidins, the percentage of degradation
      was significantly lower, between 12 and 30%, indicating that this cooking
      procedure can preserve anthocyanidin degradation.

PMID- 19845349
TI  - Changes in antioxidative capacity of saithe (Pollachius virens) and shrimp
      (Pandalus borealis) during in vitro digestion.
AB  - The health effects of seafood have primarily been linked to eicosapentaenoic acid
      (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). These omega-3 fatty acids
      are highly susceptible to oxidation. Peptides exhibiting antioxidative capacity
      (AOC) are encrypted in seafood muscle proteins. Such components may protect the
      fatty acids during digestion and uptake, as well as exhibit antioxidative effects
      in general. The oxygen radical absorbance capacity (ORAC) assay and the ferric
      reducing antioxidant power (FRAP) assay were used to study the changes in AOC of
      fish and shrimp muscle and their aqueous fractions, referred to as press juice
      (PJ), during a simulated in vitro gastrointestinal (GI) digestion. Blueberry
      (Vaccinium myrtillus), well-known for its AOC, was included for comparison.
      During digestion the AOC increased in all samples. After digestion the AOC of
      muscle of both autumn saithe and shrimp were higher (130-165 micromol/g), and
      winter saithe comparable (110 micromol/g) to digested blueberry when measured by
      ORAC. The AOC of PJ was low in general (5-20 micromol/g). When measured by FRAP,
      blueberry exhibited ten times the AOC of seafood muscle. Antioxidative compounds
      in seafood increased significantly during digestion, and may offer protection of
      other beneficial food components such as EPA and DHA.

PMID- 19845350
TI  - The optimization of extraction of antioxidants from apple pomace by pressurized
      liquids.
AB  - Pressurized liquid extraction (PLE) is a green extraction technique that can
      enhance extraction rates of bioactive compounds. PLE was used to extract
      antioxidants and polyphenols from industrially generated apple pomace at two
      different temperature ranges: 160 to 193 degrees C and 75 to 125 degrees C.
      Antioxidant activity (DPPH radical scavenging test), total phenol content and
      three individual polyphenol groups were determined. Response surface methodology
      was used to optimize the five response values. Maximum antioxidant activity was
      obtained at a temperature of 200 degrees C, but unwanted compounds such as
      hydroxymethylfurfural were formed. Therefore a lower temperature range between 75
      and 125 degrees C is recommended. Using this temperature range, a maximum
      antioxidant activity was determined at 60% ethanol and 102 degrees C. By using
      PLE the antioxidant activity was increased 2.4 times in comparison to traditional
      solid-liquid extraction, and the technique may be a promising alternative to
      conventional techniques for extracting antioxidants.

PMID- 19845351
TI  - Single-colloidal particle impedance spectroscopy: complete equivalent circuit
      analysis of polyelectrolyte microcapsules.
AB  - We present a high-speed microfluidic technique for characterizing the dielectric
      properties of individual polyelectrolyte microcapsules with different shell
      thicknesses using single-particle electrical impedance spectroscopy. Complete
      equivalent circuit analysis is developed to describe the electrical behavior of
      solid homogeneous microparticles and shelled microcapsules in suspension. The
      complete circuit model, which includes the resistance of the shell layer and the
      capacitance of the inner core, has been used to determine the permittivity and
      conductivity in the shell of single capsules. The PSpice circuit simulations,
      based on the developed complete circuit models, are used to analyze the
      experimental data. The relative permittivity of the polyelectrolyte capsule shell
      is determined to be 50, and the conductivities of the shells of six- and nine
      layer microcapsules are estimated to be 28 +/- 6 and 3.3 +/- 1.7 mS m(-1),
      respectively.

PMID- 19845352
TI  - Effect of season on the chemical composition and nutritional quality of the
      edible crab Cancer pagurus.
AB  - Cancer pagurus is most appreciated in southern Europe for its muscle and brown
      meat content. In Portugal, consumption occurs mostly in summer and at Christmas.
      In this study the seasonal nutritional quality of edible tissues of female and
      male C. pagurus was determined. Tissue composition was affected by season and
      sex. All tissues had a well-balanced essential amino acid composition. Muscle and
      gonads of females had n-3/n-6 ratios in the range of the usual recommended
      values, and all tissues had PUFA/SFA above the recommended level. Autumn was the
      season with the highest brown meat yield, total essential amino acids (muscle),
      taurine (all tissues), EPA (male gonads), and n-3/n-6 ratio (gonads). However, it
      was also the season with the highest fat content and cholesterol concentration in
      ovaries. Therefore, people with restricted diets should moderate the consumption
      of ovaries in autumn. The remaining tissues pose no risks with respect to their
      proximate chemical composition.

PMID- 19845353
TI  - Compound K induces apoptosis via CAMK-IV/AMPK pathways in HT-29 colon cancer
      cells.
AB  - Although compound K (CK), an intestinal metabolite of ginseng protopanaxadiol
      saponins, has been known to induce apoptosis in various cancer cells, association
      of AMP-activated protein kinase (AMPK) with apoptosis in HT-29 colon cancer cells
      remains unclear. We hypothesized that CK may exert an anticancer activity through
      modulating the AMPK pathway in HT-29 cells. CK-induced apoptosis was associated
      with the disruption of the mitochondrial membrane potential, release of
      apoptogenic factors (cytochrome c and apoptosis-inducing factor) from
      mitochondria, and cleavage of caspase-9, caspase-3, caspase-8, Bid, and PARP
      proteins. This apoptotic effect of CK on colon cancer cells was found to be
      initiated by AMPK activation, and AMPK was activated through phosphorylation by
      Ca2+/calmodulin-activated protein kinase-IV (CAMK-IV). Treatment of HT-29 cells
      with compound C (AMPK inhibitor) or siRNA for AMPK completely abolished the CK
      induced apoptosis. STO-609, CAMKs inhibitor, also attenuated CK-induced AMPK
      activation and apoptosis. In conclusion, the present study demonstrates that CK
      mediated cell death of HT-29 colon cancer cells is regulated by CAMK-IV/AMPK
      pathways, and these findings provide a molecular basis for the anticancer effect
      of CK.

PMID- 19845354
TI  - Interactions between wine volatile compounds and grape and wine matrix components
      influence aroma compound headspace partitioning.
AB  - A full-factorial design was used to assess the matrix effects of ethanol,
      glucose, glycerol, catechin, and proline on the volatile partitioning of 20
      volatile compounds considered to play a role in wine aroma. Analysis of variance
      showed that the two-way interactions of ethanol and glucose, ethanol and
      glycerol, and glycerol and catechin significantly influenced headspace
      partitioning of volatiles. Experiments were conducted to observe the effect of
      varied ethanol and glucose concentrations on headspace partitioning of a constant
      concentration of volatiles. Analysis of variance and linear regression analysis
      showed that the presence of glucose increased the concentration of volatiles in
      the headspace, whereas increasing ethanol concentration was negatively correlated
      with headspace partitioning of volatiles. A subsequent study assessed the effect
      of diluting white and red wines with water and ethanol. It was again observed
      that increased ethanol concentration significantly reduced the relative abundance
      of volatile compounds in the sample headspace. This study investigates some of
      the complex matrix interactions of the major components of grape and wine that
      influence volatile compound headspace partitioning. The magnitude of each matrix
      volatile interaction was ethanol > glucose > glycerol > catechin, whereas proline
      showed no apparent interaction. The results clearly identify that increasing
      ethanol concentrations significantly reduce the headspace concentration of
      volatile aroma compounds, which may contribute to explaining recent sensory
      research observations that indicate ethanol can suppress the fruit aroma
      attributes in wine.

PMID- 19845355
TI  - Structure determination of bisacetylenic oxylipins in carrots (Daucus carota L.)
      and enantioselective synthesis of falcarindiol.
AB  - Although bisacetylenic oxylipins have been demonstrated to exhibit diverse
      biological activities, the chemical structures of many representatives of this
      class of phytochemicals still remain elusive. As carrots play an important role
      in our daily diet and are known as a source of bisacetylenes, an extract made
      from Daucus carota L. was screened for bisacetylenic oxylipins, and, after
      isolation, their structures were determined by means of LC-MS and 1D/2D NMR
      spectroscopy. Besides the previously reported falcarinol, falcarindiol, and
      falcarindiol 3-acetate, nine additional bisacetylenes were identified, among
      which six derivatives are reported for the first time in literature and three
      compounds were previously not identified in carrots. To determine the absolute
      stereochemistry of falcarindiol in carrots, the (3R,8R)-, (3R,8S)-, (3S,8R)-, and
      (3S,8S)-stereoisomers of falcarindiol were synthesized according to a novel 10
      step total synthesis involving a Cadiot-Chodkiewicz cross-coupling reaction of
      (S)- and (R)-trimethylsilanyl-4-dodecen-1-yn-3-ol and (R)- and (S)-5-bromo-1
      penten-4-yn-3-ol, respectively. Comparative chiral HPLC analysis of the synthetic
      stereoisomers with the isolated phytochemical led to the unequivocal assignment
      of the (Z)-(3R,8S)-configuration for falcarindiol in carrot extracts from Daucus
      carota L.

PMID- 19845356
TI  - Heavy atom ferromagnets under pressure: structural changes and the magnetic
      response.
AB  - Application of physical pressure to a ferromagnetic bisdiselenazolyl radical
      leads to a decrease in pi-stack slippage. Initially, this leads to an increase in
      the ferromagnetic ordering temperature T(C), which reaches a maximum of 21 K near
      1 GPa. At higher pressures, as the pi-stacks become more nearly superimposed, the
      value of T(C) diminishes.

PMID- 19845357
TI  - ESI-MS, DFT, and synthetic studies on the H(2)-mediated coupling of acetylene:
      insertion of C=X bonds into rhodacyclopentadienes and Bronsted acid cocatalyzed
      hydrogenolysis of organorhodium intermediates.
AB  - The catalytic mechanism of the hydrogen-mediated coupling of acetylene to
      carbonyl compounds and imines has been examined using three techniques: (a) ESI
      MS and ESI-CAD-MS analyses, (b) computational modeling, and (c) experiments
      wherein putative reactive intermediates are diverted to alternate reaction
      products. ESI-MS analysis of reaction mixtures from the hydrogen-mediated
      reductive coupling of acetylene to alpha-ketoesters or N-benzenesulfonyl
      aldimines corroborate a catalytic mechanism involving C horizontal lineX (X = O,
      NSO(2)Ph) insertion into a cationic rhodacyclopentadiene obtained by way of
      acetylene oxidative dimerization with subsequent Bronsted acid cocatalyzed
      hydrogenolysis of the resulting oxa- or azarhodacycloheptadiene. Hydrogenation of
      1,6-diynes in the presence of alpha-ketoesters provides analogous coupling
      products. ESI mass spectrometric analysis again corroborates a catalytic
      mechanism involving carbonyl insertion into a cationic rhodacyclopentadiene. For
      all ESI-MS experiments, the structural assignments of ions are supported by
      multistage collisional activated dissociation (CAD) analyses. Further support for
      the proposed catalytic mechanism derives from experiments aimed at the
      interception of putative reactive intermediates and their diversion to alternate
      reaction products. For example, rhodium-catalyzed coupling of acetylene to an
      aldehyde in the absence of hydrogen or Bronsted acid cocatalyst provides the
      corresponding (Z)-butadienyl ketone, which arises from beta-hydride elimination
      of the proposed oxarhodacycloheptadiene intermediate, as corroborated by isotopic
      labeling. Additionally, the putative rhodacyclopentadiene intermediate obtained
      from the oxidative coupling of acetylene is diverted to the product of reductive
      [2 + 2 + 2] cycloaddition when N-p-toluenesulfonyl-dehydroalanine ethyl ester is
      used as the coupling partner. The mechanism of this transformation also is
      corroborated by isotopic labeling. Computer model studies based on density
      functional theory (DFT) support the proposed mechanism and identify Bronsted acid
      cocatalyst assisted hydrogenolysis to be the most difficult step. The collective
      studies provide new insight into the reactivity of cationic
      rhodacyclopentadienes, which should facilitate the design of related rhodium
      catalyzed C-C couplings.

PMID- 19845358
TI  - Electrospray ionization mass spectrometry of intrinsically cationized
      nanoparticles,
      [Au(144/146)(SC(11)H(22)N(CH(2)CH(3))(3)(+))(x)(S(CH(2))(5)CH(3))(y)](x+).
AB  - Electrospray ionization triple-quadrupole mass spectrometry of ca. 1.6 nm
      diameter thiolate-protected gold nanoparticles has been achieved at higher
      resolution than in previous reports. The results reveal the presence of
      nanoparticles with formulas Au(144)L(60) and Au(146)L(59), present in the sample
      as a mixture. The improved resolution is based on lowering m/z by exchanging
      multiple [-SC(11)H(22)N(CH(2)CH(3))(3)(+)] ligands into the original [
      S(CH(2))(5)CH(3)] ligand shell. The nanoparticles are thus intrinsically
      cationized and appear as a series of 10+ to 15+ mass spectral peaks. The assigned
      state of charge was confirmed by a collision-induced dissociation measurement.

PMID- 19845361
TI  - Deciphering low energy deactivation channels in adenine.
AB  - The radiationless decay paths of 9H-adenine in its lowest excited states (1)npi*,
      (1)L(b)((1)pipi*), and (1)L(a)((1)pipi*) and in dissociative (1)pisigma* states
      have been mapped in vacuo at the CASPT2//CASSCF resolution. The minimum energy
      path (MEP) of the (1)L(a) state, which shows the strongest absorption below 5 eV,
      is found to decrease monotonically along the puckering coordinate from the
      vertical excitation to a S(0)/(1)L(a) conical intersection (CI). The vertically
      excited (1)npi* and (1)L(b) states are found to relax to the respective minima
      and to require some energy to reach CIs with S(0). This picture suggests that
      (1)L(a) alone is responsible of both components of the ultrafast biexponential
      decay (with tau(1) < 0.1 ps and tau(2) < 1 ps) recently observed in time-resolved
      pump-probe resonant ionization and fluorescence spectroscopy, and that the
      (1)npi* and (1)L(b) states do not act as important intermediates in the (1)L(a)
      decay process. We find that the (1)L(a)-->(1)pisigma(N9H)* internal conversion
      can be followed by N(9)-H photocleavage, albeit with tiny quantum yield. The
      amino N(10)-H bond photocleavage is hindered by the high barrier encountered
      along the N(10)-H bond-breaking path in the (1)pisigma(N10H)* state.

PMID- 19845362
TI  - Different and more powerful, not just smaller, faster, cheaper.

PMID- 19845364
TI  - Molecular rotors and motors: recent advances and future challenges.
AB  - At the "Molecular Rotors and Motors" symposium of the Spring 2009 ACS National
      Meeting in Salt Lake City (March 22-26), a diverse mix of talks addressed many
      current issues in the field. Speakers described topics that varied from single
      molecule rotors and nanomachines to exquisite synthetic approaches toward
      building functional materials and mathematical and computational methods aimed at
      uncovering design opportunities and highlighting the fundamental limitations of
      molecular motors. While the realization of building useful nanomachines remains
      far off, a general consensus abounded that investigating biological systems and
      understanding the implications of the laws of thermodynamics and quantum
      mechanics for the behavior of nanostructures will help drive important advances
      in the quest for molecular machinery. Molecular rotors were demonstrated to have
      practical applications as probes for microviscosity, and many speakers presented
      experimental studies that indicated that highly directed translation and rotation
      of individual molecules, as well as interacting dipolar arrays, are just around
      the corner. While this Nano Focus is not intended to be a comprehensive review of
      the subject, it will focus on several key advances that were presented at the ACS
      meeting and highlight future challenges for the field of molecular rotors and
      motors.

PMID- 19845365
TI  - Nanofabrication beyond electronics.
AB  - This Nano Focus article reviews recent developments in nanofabrication based on
      invited talks given at the "Chemical Methods of Nanofabrication" symposium, which
      was organized by the authors and presented at the 237th ACS National Meeting and
      Exhibition as one of seven symposia within the meeting theme, "Nanoscience:
      Challenges for the Future". The three-day symposium included 25 experts from
      academia, national laboratories, and industry from around the world, to discuss
      current progress and future directions in nanofabrication. We highlight several
      of the key results discussed and future directions and challenges in this rapidly
      changing field.

PMID- 19845366
TI  - Quantum dot-block copolymer hybrids with improved properties and their
      application to quantum dot light-emitting devices.
AB  - To combine the optical properties of CdSe@ZnS quantum dots (QDs) with the
      electrical properties of semiconducting polymers, we prepared QD/polymer hybrids
      by grafting a block copolymer (BCP) containing thiol-anchoring moieties
      (poly(para-methyl triphenylamine-b-cysteamine acrylamide)) onto the surfaces of
      QDs through the ligand exchange procedure. The prepared QD/polymer hybrids
      possess improved processability such as enhanced solubility in various organic
      solvents as well as the film formation properties along with the improved
      colloidal stability derived from the grafted polymer shells. We also demonstrated
      light-emitting diodes based on QD/polymer hybrids, exhibiting the improved device
      performance (i.e., 3-fold increase in the external quantum efficiency) compared
      with the devices prepared by pristine (unmodified) QDs.

PMID- 19845368
TI  - Crystal structure of a cyclotetramer from a strained cyclic allene.
AB  - The low-temperature treatment of 1,1-dibromo-1a,9b-cyclopropa[l]phenanthrene (1)
      with butyllithium and copper(II) chloride in THF affords a dibenzoannellated
      1,2,4,6-cycloheptatetraene which undergoes a rare cyclotetramerization. The
      crystal structure of this "formal" 2 + 2 + 2 + 2 cyclotetramer (2) reveals a
      central eight-membered ring folded in a zigzag fashion with hydrogen atoms and
      exocyclic double bonds occupying axial positions. B3LYP/6-31+G** calculations
      indicate that the strained cyclic allene is significantly distorted and could be
      formed by ring expansion of a putative cyclopropylidene intermediate.

PMID- 19845367
TI  - Salt dependence of an alpha-helical peptide folding energy landscapes.
AB  - We used CD, UV resonance Raman spectroscopy, and molecular dynamics simulation to
      examine the impact of salts on the conformational equilibria and the Ramachandran
      Psi angle (un)folding Gibbs free energy landscape coordinate of a mainly
      polyalanine alpha-helical peptide, AP of sequence AAAAA(AAARA)(3)A. NaClO(4)
      stabilizes alpha-helical-like conformations more than does NaCl, which stabilizes
      more than Na(2)SO(4) at identical ionic strengths. This alpha-helix stabilization
      ordering is the reverse of the Hofmeister series of anions in their ability to
      disorder water hydrogen bonding. Much of the NaClO(4) alpha-helix stabilization
      results from ClO(4)(-) association with the AP terminal -NH(3)(+) groups and Arg
      side chains. ClO(4)(-) stabilizes 3(10)-helix conformations but destabilizes turn
      conformations. The decreased Cl(-) and SO(4)(2-) AP alpha-helix stabilization
      probably results from a decreased association with the Arg and terminal -NH(3)(+)
      groups. Cl(-) is expected to have a smaller binding affinity and thus stabilizes
      alpha-helical conformations intermediately between NaClO(4) and Na(2)SO(4).
      Electrostatic screening stabilizes pi-bulge conformations.

PMID- 19845369
TI  - Modular synthesis of heterobimetallic salen structures using metal templation.
AB  - A modular and general synthetic method is disclosed for nonsymmetrical
      heterobimetallic bis-salphen structures starting from a series of synthetically
      convenient monometalated triimine precursors. This methodology permits the
      introduction of various combinations of metal ions within the bis-salphen
      framework potentially useful in multifunctional materials.

PMID- 19845370
TI  - Mechanical probing of icelike water monolayers.
AB  - Direct measurements of the normal force interactions between a mica-tungsten
      contact pair at various humidity levels reveal the presence of repulsive forces
      at about 0.5 nm before intimate contact. Such repulsive interactions begin to
      appear above 20% RH and are fully developed in the range of 38-45% RH. Using the
      DMT model of contact, a reduced elastic modulus of approximately 6.7 GPa is
      extracted from these repulsive interactions and attributed to the presence of
      icelike water on mica at room temperature. The collapse of such structures was
      also inferred from the measurements.

PMID- 19845371
TI  - Quantitative structure-activity relationship modeling of rat acute toxicity by
      oral exposure.
AB  - Few quantitative structure-activity relationship (QSAR) studies have successfully
      modeled large, diverse rodent toxicity end points. In this study, a comprehensive
      data set of 7385 compounds with their most conservative lethal dose (LD(50))
      values has been compiled. A combinatorial QSAR approach has been employed to
      develop robust and predictive models of acute toxicity in rats caused by oral
      exposure to chemicals. To enable fair comparison between the predictive power of
      models generated in this study versus a commercial toxicity predictor, TOPKAT
      (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the
      entire data set was selected that included all 3472 compounds used in TOPKAT's
      training set. The remaining 3913 compounds, which were not present in the TOPKAT
      training set, were used as the external validation set. QSAR models of five
      different types were developed for the modeling set. The prediction accuracy for
      the external validation set was estimated by determination coefficient R(2) of
      linear regression between actual and predicted LD(50) values. The use of the
      applicability domain threshold implemented in most models generally improved the
      external prediction accuracy but expectedly led to the decrease in chemical space
      coverage; depending on the applicability domain threshold, R(2) ranged from 0.24
      to 0.70. Ultimately, several consensus models were developed by averaging the
      predicted LD(50) for every compound using all five models. The consensus models
      afforded higher prediction accuracy for the external validation data set with the
      higher coverage as compared to individual constituent models. The validated
      consensus LD(50) models developed in this study can be used as reliable
      computational predictors of in vivo acute toxicity.

PMID- 19845372
TI  - Metal-free reductive cleavage of C-O sigma-bonds in acyloin derivatives by an
      organic neutral super-electron-donor.
AB  - Neutral organic electron-donor 7, formally a pyridinylidene carbene dimer,
      effects reductive cleavage of C-O sigma-bonds in acyloin derivatives Ar(CO)CRR'OX
      (X = OAc, OPiv, OBz, OMs) and this represents the first cleavage of C-O sigma
      bonds by a neutral organic electron-donor. The methodology is applicable to a
      large array of substrates and the reduced counterparts were isolated in good to
      excellent yields. For certain substrates, donor 7 behaves as a base, effecting
      condensation reactions with some acetate ester derivatives of acyloins, leading
      to butenolides. The variation in reactivity among the different substrates was
      rationalized.

PMID- 19845373
TI  - Fabrication of hollow poly(lactic acid) microcapsules from microbubble templates.
AB  - Hollow microcapsules are expected to be integral components of drug delivery
      systems in medical and pharmaceutical applications. Among the methods studied,
      the bubble template method (Makuta et al. Mater. Lett. 2009, 63, 703-705) should
      easily fabricate uniform hollow microcapsules covered with biodegradable
      polymers. In this study, we clarified the two conditions required to fabricate
      uniform hollow microcapsules using the bubble template method: the stability of
      uniformly sized microbubbles in a liquid droplet and the release of hollow
      microcapsules from the droplet. Furthermore, our experiments evaluated the radius
      distributions of template microbubbles and fabricated hollow poly(lactic acid)
      microcapsules.

PMID- 19845374
TI  - Construction and charge-transfer complexation of adamantane-based macrocycles and
      a cage with aromatic ring moieties.
AB  - Adamantane-based macrocycles and a cage with aromatic ring moieties have been
      developed and structurally revealed by X-ray crystallographic analysis. The
      dimerized (1) and trimerized (2) macrocycles of binary molecules based on
      adamantane with acetylenic aromatic ring moieties were designed and effectively
      synthesized. Similarly, a cryptand-like macrobicyclic cage (3) was constructed
      from a trisubstituted adamantane derivative. Single-crystal X-ray analysis
      revealed that both cyclic compounds have nearly a rectangular shape with or
      without a solvent molecule in the cavity. The macrobicyclic cage has an inner
      space and accommodates a chloroform molecule via C-H...pi interactions.
      Macrocycles and cage encapsulate 1,3,5-trinitrobenzene (4) as an electron-poor
      guest in a one-to-one complex via charge-transfer interactions in a parallel
      fashion, and showed the formation of molecular networks such as columns, tubes,
      2D layers, and 3D networks composed of two different types through noncovalent
      interactions in the solid state.

PMID- 19845375
TI  - Design and evaluation of nonfluorous CO2-soluble oligomers and polymers.
AB  - Ab initio molecular modeling is used to design nonfluorous polymers that are
      potentially soluble in liquid CO2. We have used calculations to design three
      nonfluorous compounds meant to model the monomeric repeat units of polymers that
      exhibit multiple favorable binding sites for CO2. These compounds are methoxy
      isopropyl acetate, 2-methoxy ethoxy-propane, and 2-methoxy methoxy-propane. We
      have synthesized oligomers or polymers based on these small compounds and have
      tested their solubility in CO2. All three of these exhibit appreciable solubility
      in CO2. At 25 degrees C, oligo(3-acetoxy oxetane)6 is 5 wt % soluble at 25 MPa,
      the random copolymer (vinyl methoxymethyl ether30-co-vinyl acetate9) is 5 wt %
      soluble at 70 MPa and random copolymer (vinyl 1-methoxyethyl ether30-co-vinyl
      acetate9) is 3 wt % soluble at 120 MPa. These oligomers and polymers represent
      new additions to the very short list of nonfluorous CO2-soluble polymers.
      However, none of these are more soluble than poly(vinyl acetate), which exhibits
      the highest CO2 solubility of any known polymer containing only the elements C,
      H, and O.

PMID- 19845376
TI  - Photophysics of 1-aminonaphthalene: a theoretical and time-resolved experimental
      study.
AB  - The photophysics of 1-aminonaphthalene (1-napthylamine, AMN) has been
      investigated on the basis of a constructive experimental-theoretical interplay
      derived from time-resolved measurements and high-level quantum-chemical ab initio
      CASPT2//CASSCF calculations. Transient ionization signals at femtosecond
      resolution were collected for AMN cold isolated molecules following excitation
      from the vibrationless ground level to a number of vibrational states (within the
      pump resolution) in the lowest accessible excited state and further multiphoton
      ionization probing at 500, 800, and 1300 nm. Theory predicts two pipi* states,
      (1)L(b) and (1)L(a), as the lowest singlet electronic excitations, with adiabatic
      transitions from S(0) at 3.50 and 3.69 eV, respectively. Since the associated
      oscillator strength for the lowest transition is exceedingly small, the (1)L(b)
      state is not expected to become populated significantly and the (1)L(a) state
      appears as the main protagonist of the AMN photophysics. Though calculations
      foresee a surface crossing between (1)L(a) and the lower (1)L(b) states, no
      dynamical signature of it is observed in the time-dependent measurements. In the
      relaxation of (1)L(a), the radiant emission competes with the intersystem
      crossing and internal conversion channels. The rates of these mechanisms have
      been determined at different excitation energies. The internal conversion is
      mediated by a (1)L(a)/S(0) conical intersection located 0.7 eV above the (1)L(a)
      minimum. The relaxation of a higher-lying singlet excited state, observed above
      40 000 cm(-1) (4.96 eV) and calculated at 5.18 eV, has been also explored.

PMID- 19845377
TI  - A large-scale quantitative proteomic approach to identifying sulfur mustard
      induced protein phosphorylation cascades.
AB  - Sulfur mustard [SM, bis-(2-chloroethyl) sulfide] is a potent alkylating agent and
      chemical weapon. While there are no effective treatments for SM-induced injury,
      current research focuses on understanding the molecular changes upon SM exposure.
      Indeed, efforts that seek a more comprehensive analysis of proteins and post
      translational modifications are critical for understanding SM-induced toxicity on
      a more global scale. Furthermore, these studies can uncover proteins previously
      uncharacterized in SM-exposed cells, which in turn leads to potential targets for
      therapeutic intervention. Here, we apply a quantitative proteomic approach termed
      stable isotope-labeling with amino acids in cell culture combined with
      immobilized metal affinity chromatography to study the large-scale protein
      phosphorylation changes resulting from SM exposure in a human keratinocyte cell
      culture model. This resulted in the characterization of over 2300 nonredundant
      phosphorylation sites, many of which exhibit altered levels in response to SM.
      Our results point toward several proteins previously implicated in SM-induced
      toxicity as well as many additional proteins previously uncharacterized. Further
      de novo analysis of these phosphoproteins using interaction mapping software
      revealed both known and novel pathways that may serve as future therapeutic
      targets of SM exposure.

PMID- 19845378
TI  - DNA-based supramolecular artificial light harvesting complexes.
AB  - Solar radiation reaching this planet is distributed over a wide range of
      wavelengths, and efficient collection and conversion of solar energy requires
      light harvesting over multiple wavelengths. Yet, the design, synthesis, and
      testing of novel, efficient, inexpensive light harvesting complexes are lacking.
      Engineered protein-DNA complexes are used here to self-assemble donor and
      acceptor molecules into artificial light harvesting units with an association
      constant of 3.3 +/- 1.2 muM(-1). Excitation of the DNA-bound donors resulted in a
      540% increase in emission from the protein-bound acceptors, and the presence of
      one acceptor for each pair of donors was sufficient to quench approximately 50%
      of donor emission. Successful self-assembly of DNA-based light harvesting units
      is expected to facilitate economic/efficient conversion of solar energy, and
      model systems to achieve this goal are demonstrated here. We anticipate that
      success along these lines would facilitate more efficient approaches for solar
      energy capture.

PMID- 19845379
TI  - Deconvolution of complex NMR spectra in small molecules by multi frequency
      homonuclear decoupling (MDEC).
AB  - A new technique to deconvolute complex (1)H NMR spectra of small molecules has
      been developed that utilizes shape selective pulses to simultaneously decouple
      multiple protons. A limitation in the assignment of the relative configuration of
      small molecules is the ability to accurately obtain coupling constants. Other
      methods such as the E.COSY and the 2D J-resolved are available to obtain
      complicated coupling constants; the multiple homonuclear decoupling method (MDEC)
      described is a rapid and simple technique. Three examples of increasing spectral
      complexity, menthol, cholesteryl acetate and a C(16) fatty acid, demonstrate the
      utility of the technique. Increasing the experimental utility, the single pulse
      MDEC experiment can be incorporated in other 1D experiments, such as a 1D-TOCSY
      to solve specific problems.

PMID- 19845380
TI  - Synthesis and modeling of polysiloxane-based salt-in-polymer electrolytes with
      various additives.
AB  - The effect of both nanoparticles and low molecular weight borate esters on the
      ionic conductivity of cross-linked polysiloxanes was systematically investigated
      by means of measuring conductivity spectra in the impedance regime at
      temperatures between -30 and 90 degrees C. Salt-in-polymer electrolytes were
      prepared by dissolving lithium triflate (LiSO(3)CF(3)) in comblike polysiloxanes
      bearing one methyl and one oligoether side group per silicon. An amount of 10 mol
      % of the oligoether side groups exhibited a terminal allytrimethoxysilane serving
      as a cross-linker moiety (T(0.1)OPS). Thus prepared polymer electrolyte membranes
      were completely amorphous and mechanically stable with an optimum conductivity
      value of 5.7 x 10(-5) S x cm(-1) at 15 wt % of lithium triflate (LiSO(3)CF(3)) at
      room temperature (T(0.1)OPS + 15 wt % LiSO(3)CF(3)). Further investigations
      concerned the influence of additives, i.e., nanosized ceramic fillers (alpha
      Al(2)O(3) and SiO(2), up to 10 wt %) as well as two low molecular weight borate
      esters (tris(2-(2-methoxyethoxy)ethyl) borate (B2) and tris(2-(2-(2
      methoxyethoxy)ethoxy)ethyl) borate (B3)) with maximum concentrations of 40 wt %
      as referred to polysiloxane T(0.1)OPS. The addition of borate esters resulted in
      a considerable increase of the conductivity, while still maintaining the
      mechanical stability. Optimum conductivities of 3.7 x 10(-5) and 1.6 x 10(-4) S x
      cm(-1) were measured for B2 and B3, respectively, at room temperature. A fit of
      the temperature-dependent DC conductivity by the empirical Vogel-Tammann-Fulcher
      (VTF) equation showed that there was an increased number density of mobile charge
      carriers in the case of borate esters as additives. However, the shape of the
      conductivity spectra in the dispersive regime changed considerably in going from
      nanoparticles as additives to borate esters. A careful and consistent modeling of
      the conductivity spectra and of the temperature dependence of the DC conductivity
      was done within the framework of the MIGRATION concept. The result was that the
      addition of borate esters to the polymer host most probably increased both number
      density of mobile charge carriers as well as their mobility.

PMID- 19845381
TI  - Oxygen exchange in the selective oxidation of 2-butanol on oxygen precovered
      Au(111).
AB  - Direct evidence for C-O bond cleavage in the partial oxidation of 2-butanol on
      oxygen precovered Au(111) is provided using temperature programmed desorption
      (TPD) and molecular beam reactive scattering (MBRS) under ultrahigh vacuum (UHV)
      conditions. The oxygen precovered Au(111) surface can promote the partial
      oxidation of 2-butanol into 2-butanone with near 100% selectivity at low oxygen
      coverages, while 2-butanol adsorbs and desorbs molecularly on the clean Au(111)
      surface. Both C(2)H(5)C(16)OCH(3) and C(2)H(5)C(18)OCH(3) are observed in TPD
      after 2-butanol (C(2)H(5)CH(16)OHCH(3)) was dosed onto Au(111) precovered with
      (18)O(a). This oxygen exchange phenomenon serves as strong evidence for the C-O
      bond cleavage in 2-butanol partial oxidation to 2-butanone. Two surface
      intermediates are proposed for the selective oxidation of 2-butanol: 2-butoxide
      and eta(2)-aldehyde. As oxygen coverage increases, full oxidation is activated in
      addition to selective partial oxidation.

PMID- 19845382
TI  - The tellurophosphate K(4)P(8)Te(4): phase-change properties, exfoliation,
      photoluminescence in solution and nanospheres.
AB  - We describe the inorganic polymer K(4)P(8)Te(4) which is soluble, giving
      solutions that exhibit white emission upon 355 nm laser irradiation. An indirect
      band gap semiconductor (E(g) approximately 1.4 eV), K(4)P(8)Te(4) crystallizes in
      the space group P2(1)/m, with a = 6.946(1) A, b = 6.555(1) A, c = 9.955(2) A, and
      beta = 90.420(3) degrees at 173(2) K. The compound features infinite chains of
      [P(8)Te(4)(4-)] with covalent P-Te bonding and exhibits reversible crystal-glass
      phase-change behavior. When deposited from solution, the material forms highly
      crystalline K(4)P(8)Te(4) nanospheres. The thermal analysis, FT-IR, UV-vis
      diffuse reflectance, (31)P magic angle spinning solid-state NMR spectroscopy, and
      pair distribution function (PDF) analysis for the crystal and glass forms and ab
      initio electronic structure calculations by the screened-exchange local density
      function approximation are also reported. Speciation of K(4)P(8)Te(4) in solution
      studied with (31)P solution-state NMR spectroscopy, electrospray ionization mass
      spectrometry, and PDF analysis indicate exfoliation of [P(8)Te(4)(4-)] chains
      followed by rearrangement into molecular species.

PMID- 19845383
TI  - A nonmetal catalyst for molecular hydrogen activation with comparable catalytic
      hydrogenation capability to noble metal catalyst.
AB  - Fullerene can activate molecular hydrogen and is a novel nonmetal hydrogenation
      catalyst. The hydrogenation of aromatic nitro compounds to amino aromatics is
      achieved on this catalyst with high conversion and selectivity under 1
      atmospheric pressure of H(2) and light irradiation at room temperature or under
      conditions of 120-160 degrees C and 4-5 MPa H(2) pressure without light
      irradiation, which is comparable to the case with a noble metal catalyst.

PMID- 19845384
TI  - Thermal decomposition of gaseous ammonium nitrate at low pressure: kinetic
      modeling of product formation and heterogeneous decomposition of nitric acid.
AB  - The thermal decomposition of ammonium nitrate, NH(4)NO(3) (AN), in the gas phase
      has been studied at 423-56 K by pyrolysis/mass spectrometry under low-pressure
      conditions using a Saalfeld reactor coated with boric acid. The sublimation of
      NH(4)NO(3) at 423 K was proposed to produce equal amounts of NH(3) and HNO(3),
      followed by the decomposition reaction of HNO(3), HNO(3) + M --> OH + NO(2) + M
      (where M = third-body and reactor surface). The absolute yields of N(2), N(2)O,
      H(2)O, and NH(3), which can be unambiguously measured and quantitatively
      calibrated under a constant pressure at 5-6.2 torr He are kinetically modeled
      using the detailed [H,N,O]-mechanism established earlier for the simulation of
      NH(3)-NO(2) (Park, J.; Lin, M. C. Technologies and Combustion for a Clean
      Environment. Proc. 4th Int. Conf. 1997, 34-1, 1-5) and ADN decomposition
      reactions (Park, J.; Chakraborty, D.; Lin, M. C. Proc. Combust. Inst. 1998, 27,
      2351-2357). Since the homogeneous decomposition reaction of HNO(3) itself was
      found to be too slow to account for the consumption of reactants and the
      formation of products, we also introduced the heterogeneous decomposition of
      HNO(3) in our kinetic modeling. The heterogeneous decomposition rate of HNO(3),
      HNO(3) + (B(2)O(3)/SiO(2)) --> OH + NO(2) + (B(2)O(3)/SiO(2)), was determined by
      varying its rate to match the modeled result to the measured concentrations of
      NH(3) and H(2)O; the rate could be represented by k(2b) = 7.91 x 10(7) exp(-12
      600/T) s(-1), which appears to be consistent with those reported by Johnston and
      co-workers (Johnston, H. S.; Foering, L.; Tao, Y.-S.; Messerly, G. H. J. Am.
      Chem. Soc. 1951, 73, 2319-2321) for HNO(3) decomposition on glass reactors at
      higher temperatures. Notably, the concentration profiles of all species measured
      could be satisfactorily predicted by the existing [H,N,O]-mechanism with the
      heterogeneous initiation process.

PMID- 19845385
TI  - Acid dissociation constants of melamine derivatives from density functional
      theory calculations.
AB  - Melamine and its hydrolysis products (ammeline, ammelide, and cyanuric acid)
      recently attracted great attention as major food contaminants. Developing
      analytical tools to quantify them requires exact knowledge of their acid
      dissociation constants (pK(a) values). Herein, we calculated the pK(a) values of
      these melamine derivatives in water, using a density functional theory quantum
      mechanical method [B3LYP/6-311++G(d,p)] in combination with the Poisson-Boltzmann
      continuum solvation model. The excellent agreement of the calculated values with
      the experimental ones shows that our method can be used to predict such
      properties of other food contaminants.

PMID- 19845386
TI  - Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective
      activity.
AB  - DHEA analogues with modifications at positions C3 or C17 were synthesized and
      evaluated for neuroprotective activity against the neural-crest-derived PC12 cell
      model of serum deprivation-induced apoptosis. The most potent compounds were the
      spiro-epoxy derivatives 17beta-spiro[5-androstene-17,2'-oxiran]-3beta-ol (20),
      (20S)-3beta,21-dihydroxy-17beta,20-epoxy-5-pregnene (23), and (20R)-3beta,21
      dihydroxy-17alpha,20-epoxy-5-pregnene (27) with IC(50) values of 0.19 +/- 0.01,
      99.0 +/- 4.6, and 6.4 +/- 0.3 nM, respectively. Analogues 20, 23, and 27, up to
      the micromolar range of concentrations, were unable to activate estrogen receptor
      alpha and beta (ERalpha and ERbeta) or to interfere with ER-dependent gene
      expression significantly. In addition, they were unable to stimulate the growth
      of Ishikawa, MCF-7, and LNCaP cells. Our results suggest that the spiro
      epoxyneurosteroid derivatives 20, 23, and 27 may prove to be lead molecules for
      the synthesis of novel neuroprotective agents.

PMID- 19845387
TI  - 18F stilbenes and styrylpyridines for PET imaging of A beta plaques in
      Alzheimer's disease: a miniperspective.

PMID- 19845388
TI  - Characteristics of the iodide/triiodide redox mediator in dye-sensitized solar
      cells.
AB  - Dye-sensitized solar cells (DSCs) have gained widespread interest because of
      their potential for low-cost solar energy conversion. Currently, the certified
      record efficiency of these solar cells is 11.1%, and measurements of their
      durability and stability suggest lifetimes exceeding 10 years under operational
      conditions. The DSC is a photoelectrochemical system: a monolayer of sensitizing
      dye is adsorbed onto a mesoporous TiO(2) electrode, and the electrode is
      sandwiched together with a counter electrode. An electrolyte containing a redox
      couple fills the gap between the electrodes. The redox couple is a key component
      of the DSC. The reduced part of the couple regenerates the photo-oxidized dye.
      The formed oxidized species diffuses to the counter electrode, where it is
      reduced. The photovoltage of the device depends on the redox couple because it
      sets the electrochemical potential at the counter electrode. The redox couple
      also affects the electrochemical potential of the TiO(2) electrode through the
      recombination kinetics between electrons in TiO(2) and oxidized redox species.
      This Account focuses on the special properties of the iodide/triiodide (I(
      )/I(3)(-)) redox couple in dye-sensitized solar cells. It has been the preferred
      redox couple since the beginning of DSC development and still yields the most
      stable and efficient DSCs. Overall, the iodide/triiodide couple has good
      solubility, does not absorb too much light, has a suitable redox potential, and
      provides rapid dye regeneration. But what distinguishes I(-)/I(3)(-) from most
      redox mediators is the very slow recombination kinetics between electrons in
      TiO(2) and the oxidized part of the redox couple, triiodide. Certain dyes
      adsorbed at TiO(2) catalyze this recombination reaction, presumably by binding
      iodine or triiodide. The standard potential of the iodide/triiodide redox couple
      is 0.35 V (versus the normal hydrogen electrode, NHE), and the oxidation
      potential of the standard DSC-sensitizer (Ru(dcbpy)(2)(NCS)(2)) is 1.1 V. The
      driving force for reduction of oxidized dye is therefore as large as 0.75 V. This
      process leads to the largest internal potential loss in DSC devices. We expect
      that overall efficiencies above 15% might be achieved if half of this internal
      potential loss could be gained. The regeneration of oxidized dye with iodide
      leads to the formation of the diiodide radical (I(2)(-*)). The redox potential of
      the I(2)(-*)/I(-) couple must therefore be considered when determining the actual
      driving force for dye regeneration. The formed I(2)(-*) disproportionates to
      I(3)(-) and I(-), which leads to a large loss in potential energy.

PMID- 19845389
TI  - Nanowire biocompatibility in the brain--looking for a needle in a 3D stack.
AB  - We investigated the brain-tissue response to nanowire implantations in the rat
      striatum after 1, 6, and 12 weeks using immunohistochemistry. The nanowires could
      be visualized in the scar by confocal microscopy (through the scattered laser
      light). For the nanowire-implanted animals, there is a significant astrocyte
      response at week 1 compared to controls. The nanowires are phagocytized by ED1
      positive microglia, and some of them are degraded and/or transported away from
      the brain.

PMID- 19845390
TI  - Anomalous microbial transformations on the taxane ring of 10-DAB by a strain of
      the fungus Curvularia lunata: transbenzoylation, transacetylation, and opening of
      the oxetane ring.
AB  - The fermentation of 10-deacetylbaccatin III (10-DAB) (1) with Curvularia lunata
      afforded the taxane hemiacetals 2a and 3, characterized by extensive structural
      modification, including C-2 to C-1 transbenzoylation, oxidation of the C-2
      hydroxyl, formation of a C-9/C13 hemiacetal, epimerization at C-10, and migration
      of the endocyclic double bond to an exocyclic location. In compound 3, an acetate
      assisted opening of the oxetane ring was also observed.

PMID- 19845391
TI  - Meehanines L-W, spermidine alkaloidal glycosides from Meehania urticifolia.
AB  - Twelve new spermidine alkaloidal glycosides, meehanines L-W (1-12), were isolated
      from the whole plant Meehania urticifolia. The structures of these new compounds
      were elucidated on the basis of spectroscopic data analyses.

PMID- 19845392
TI  - Synthesis and antibacterial properties of (-)-nor-platencin.
AB  - An asymmetric Diels-Alder reaction between acrolein and 1-benzyloxymethyl-1,3
      cyclohexadiene affords a bicyclic aldehyde that was elaborated in 11 steps to nor
      platencin. nor-Platencin is 4-16 times less active than platencin against several
      resistant strains of Staphylococcus aureus, macrolide-resistant Enterococcus
      faecalis, and vancomycin-resistant Enterococcus faecium.

PMID- 19845393
TI  - Polymer brushes via surface-initiated controlled radical polymerization:
      synthesis, characterization, properties, and applications.

PMID- 19845394
TI  - Formation of pseudoisocyanine J-aggregates in poly(vinyl alcohol) fibers by
      electrospinning.
AB  - Submicrometer diameter, light emitting fibers of poly(vinyl alcohol) (PVA) doped
      with pseudoisocyanine (1,1'-diethyl-2,2'-cyanine bromide, PIC) dye were prepared
      by electrospinning. A horizontal setup was employed with a stationary collector
      consisting of two parallel-positioned metal strips separated by a void gap.
      Formation of uniaxially aligned and randomly deposited fibers in electrospun
      films was confirmed by microscopy. Photoluminescence (PL) spectroscopy is used to
      evaluate spectral properties of both types of fibers doped with PIC. While PIC
      molecules were individually dispersed in PVA solution, they assemble into J
      aggregates upon electrospinning when the weight fraction of PIC molecules is
      above 2.5 wt %. The formation of J-aggregates was observed in both randomly
      deposited and uniaxially aligned electrospun fibers. Moreover, the fibers aligned
      uniaxially showed a high degree of polarized emission
      (PLparallel/PLperpendicular=10), arising from the orientation of J-aggregates
      along the fiber axis. On the other hand, isotropic emission of J-aggregates was
      observed from the fibers deposited randomly. As a conclusion, electrospinning was
      found to be an efficient and a practical method to form highly oriented J
      aggregates dispersed into polymer fibers. To the best of our knowledge, it is the
      first time formation of J-aggregates (a bottom-up approach) and electrospinning
      (a top-down approach) is successfully combined.

PMID- 19845395
TI  - Pulse-front propagation and interaction during the growth of CdS nanoparticles in
      a gel.
AB  - We studied the spatiotemporal dynamics of a new system consisting of sulfide ions
      (outer electrolyte) diffusing into an organic gel (gelatin) containing
      mercaptoethanol-capped cadmium ions (inner electrolyte). The product, cadmium
      sulfide, exhibits a faint yellow transparent propagating front starting at the
      gel-outer electrolyte interface. When subjected to UV light, this system reveals
      fluorescing CdS nuclei localized spatially in a narrow region, called pulse, that
      leads the front and propagates down the tube. We show that the pulse consists of
      CdS nanoclusters of an average size of about 4 nm, whereas the trailing front
      consists of 6-8 nm cubic-phase CdS crystallites. The width of the pulse remains
      constant in time, t, at about 2 mm and independent of the outer concentration S0.
      It was found that the speed of the pulse fluctuates as the concentration of the
      capping agent is varied, with fastest pulses attained at a concentration of 40 mM
      for two different outer concentrations of sulfide ions. The origin of the yellow
      fluorescence of the pulse originates from emission from surface states. This
      dynamical system was then theoretically studied using a competitive particle
      growth model. The resulting evolution equations were solved numerically, and the
      results were compared to the experimental findings. It was shown that the model
      agrees in many aspects with the experiment. The densities of small particles and
      large particles rho were shown to evolve like a pulse and a front, respectively.
      The front was shown to extend "diffusively" as t1/2, as found experimentally. The
      distance traveled by the pulse xpeak was shown to increase with outer
      concentration S0 and obeys a concentration power law xpeak approximately S(0)1/4.
      The width w of the pulse also obeys a time power law w approximately ta with a
      crossover between early times (a=1/3) and intermediate times (a=0). This system
      would enable us to study the early time dynamics of Liesegang systems.

PMID- 19845396
TI  - Molecular dynamics simulations of the structure and thermodynamics of carrier
      assisted uranyl ion extraction.
AB  - We present molecular dynamics simulations of interfaces relevant to the selective
      chemical extraction of uranyl ions from aqueous solution. These molecular-level
      simulations model ion transfer in the PUREX process and in synthetic, selective
      membranes. We first present simulations of water/oil interfaces modified by
      incorporation of tributyl phosphate (TBP) into the oil phase (hexane). A range of
      concentrations is examined, from a single TBP molecule to values close to those
      utilized in the PUREX process. The TBP molecules exhibit strong interfacial
      activity, and the interface broadens relative to the water/oil case with
      increasing TBP concentrations. Additional structural features, including radial
      distribution functions and orientational distributions, are examined to elucidate
      the molecular ordering at the interface; the interface structure changes
      substantially with increasing TBP concentration. Finally, free-energy profiles
      are computed for (1) a single TBP molecule and a single uranyl nitrate complex
      [UO2(NO3)2] across the water/oil interface and (2) a UO2(NO3)2.TBP2 complex
      across both water/oil and water/(oil+TBP) interfaces. The UO2(NO3)2 complex is
      strongly repelled from the water/oil interface, while the UO2(NO3)2.TBP2 complex
      exhibits interfacial activity that decreases with increasing TBP concentration.
      The UO2(NO3)2.TBP2 complex displays a net free-energy driving force for
      partitioning into the oil phase that increases with increasing TBP concentration.

PMID- 19845397
TI  - Influence of peripheral groups on the physical and chemical behavior of cinchona
      alkaloids.
AB  - While cinchona alkaloids play a key role in many applications, from medicine to
      catalysis, there is not yet a complete understanding of the reasons for their
      unique chemical behavior. Past studies have identified the chiral pocket formed
      by the two main constituting moieties of the cinchona, the quinoline and
      quinuclidine rings, as the main factor determining their physiological and
      enatioselective reactivity. That explanation, however, does not account for the
      differences observed among similar cinchona alkaloids. Here we show that subtle
      changes in the position of the substituent groups outside the central chiral
      pocket explain the disparities observed in basic physicochemical properties
      between pairs of near-enantiomers (quinine vs quinidine, cinchonidine vs
      cinchonine) such as crystal structure, solubility, and adsorption equilibrium.
      Both energetic and entropic factors need to be considered to fully account for
      the trends observed.

PMID- 19845398
TI  - Design of nontoxic analogues of cathelicidin-derived bovine antimicrobial peptide
      BMAP-27: the role of leucine as well as phenylalanine zipper sequences in
      determining its toxicity.
AB  - BMAP-27 is a cathelicidin-derived bovine antimicrobial peptide, which shows
      moderate cytotoxicity and potent antibacterial activity against a wide variety of
      microorganisms. Despite a number of studies, very little is known about the amino
      acid sequences of this peptide that controls its antibacterial and cytotoxic
      activities. Small stretches of phenylalanine and leucine zipper sequences were
      identified at the N- and C-termini of the molecule, respectively. To understand
      the structural and functional roles of these sequence elements, we synthesized
      and characterized several analogues of BMAP-27 after substituting leucine or
      phenylalanine residue(s) at a and/or d positions of the leucine and phenylalanine
      zipper sequences, respectively, with alanine. BMAP-27 analogues exhibited
      significantly reduced cytotoxicity against the human red blood (hRBC) and murine
      3T3 cells as compared to that of the wild-type peptide. Interestingly, BMAP-27
      and its analogues exhibited comparable antibacterial activity against the
      selected Gram-positive and Gram-negative bacteria. Moreover, BMAP-27 and its
      analogues exhibited similar localization and assembly onto the selected bacteria
      and induced comparable permeability in these cells. However, only BMAP-27, not
      its analogues, assembled and bound strongly onto the hRBCs and permeabilized
      them. The results indicated that not only a leucine zipper but also a
      phenylalanine zipper sequence plays an important role in maintaining the assembly
      of BMAP-27 on the mammalian cells examined here and cytotoxic activity against
      them. To the best of our knowledge, this is the first report of the evaluation of
      structural and functional roles of a phenylalanine zipper sequence in a naturally
      occurring antimicrobial peptide.

PMID- 19845399
TI  - Nuclear magnetic resonance structural characterization of substrates bound to the
      alpha-2,6-sialyltransferase, ST6Gal-I.
AB  - The alpha-2,6-sialyltransferase (ST6Gal-I) is a key enzyme that regulates the
      distribution of sialic acid-containing molecules on mammalian cell surfaces.
      However, the fact that its native form is membrane-bound and glycosylated has
      made structural characterization by X-ray crystallography of this eukaryotic
      protein difficult. Its large size ( approximately 40 kDa for just the catalytic
      domain) also poses a challenge for complete structure determination by nuclear
      magnetic resonance (NMR). However, even without complete structure determination,
      there are NMR strategies that can return targeted information about select
      regions of the protein, including information about the active site as seen from
      the perspective of its bound ligands. Here, in a continuation of a previous
      study, a spin-labeled mimic of a glycan acceptor ligand is used to identify
      additional amino acids located in the protein active site. In addition, the spin
      labeled donor is used to characterize the relative placement of the two bound
      ligands. The ligand conformation and protein-ligand contact surfaces are studied
      by transferred nuclear Overhauser effects (trNOEs) and saturation transfer
      difference (STD) experiments. The data afforded by the methods mentioned above
      lead to a geometric model of the bound substrates that in many ways carries an
      imprint of the ST6Gal-I binding site.

PMID- 19845400
TI  - Cell secretome analysis using hollow fiber culture system leads to the discovery
      of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in
      Southeast Asia. Unfortunately, most NPC victims have had metastasis when first
      diagnosed due to its deep location and vague symptoms. To date, discovery of
      sensitive and specific biomarkers for improving detection of NPC remains a
      challenge. Our previous study established a strategy for cell secretome analysis
      using a hollow fiber culture (HFC) system combined with liquid chromatography
      mass spectrometry. Herein, the above platform was used to collect NPC secretome
      for the discovery of relevant clinical biomarkers. Among 66 identified proteins,
      chloride intracellular channel 1 (CLIC1) was sieved out for intended use as a
      potential NPC biomarker candidate. Approximately 75% of NPC tissue specimens
      showed positive CLIC1 staining by IHC. The plasma levels of CLIC1 in NPC patients
      (N = 70), as presented by sandwich ELISA, were significantly higher than those in
      the healthy controls (N = 74) (mean +/- SD, 16.38 +/- 26.53 vs 2.39 +/- 5.32
      microg/mL; p = 0.00005). Using a cutoff point of 2.58 microg/mL, CLIC1
      successfully discriminated NPC from the benign healthy control group with a
      sensitivity of 63% and a specificity of 77%. The area under the receiver
      operating characteristic curve was determined to be 0.74 (95% CI, 0.652-0.818).
      The statistical analysis of CLIC1 level in plasma shows that CLIC1 could be
      applied as a marker for early detection of NPC. This is the first report for the
      detection of CLIC1 as a plasma marker. Our results indicate that the analytical
      platform could provide a feasible strategy to profile tumor cell secretome for
      identifying cancer biomarkers, and CLIC1 may be a novel plasma tumor marker for
      NPC.

PMID- 19845401
TI  - Angiotensin AT1 receptor antagonism ameliorates murine retinal proteome changes
      induced by diabetes.
AB  - Diabetic retinopathy is the most common microvascular complication caused by
      diabetes mellitus and is a leading cause of vision loss among working-age adults
      in developed countries. Understanding the effects of diabetes on the retinal
      proteome may provide insights into factors and mechanisms responsible for this
      disease. We have performed a comprehensive proteomic analysis and comparison of
      retina from C57BL/6 mice with 2 months of streptozotocin-induced diabetes and age
      matched nondiabetic control mice. To explore the role of the angiotensin AT1
      receptor in the retinal proteome in diabetes, a subgroup of mice were treated
      with the AT1 antagonist candesartan. We identified 1792 proteins from retinal
      lysates, of which 65 proteins were differentially changed more than 2-fold in
      diabetic mice compared with nondiabetic mice. A majority (72%) of these protein
      changes were normalized by candesartan treatment. Most of the significantly
      changed proteins were associated with metabolism, oxidative phosphorylation, and
      apoptotic pathways. An analysis of the proteomics data revealed metabolic and
      apoptotic abnormalities in the retina from diabetic mice that were ameliorated
      with candesartan treatment. These results provide insight into the effects of
      diabetes on the retina and the role of the AT1 receptor in modulating this
      response.

PMID- 19845402
TI  - Two-dimensional difference gel electrophoresis (DiGE) analysis of plasmas from
      dengue fever patients.
AB  - Dengue fever is the world's most important arthropod-born viral disease affecting
      humans. To contribute to a better understanding of its pathogenesis, this study
      aims to identify proteins differentially expressed in plasmas from severe dengue
      fever patients relative to healthy donors. The use of 2-D Fluorescence Difference
      Gel Electrophoresis to analyze plasmas depleted of six high-abundance proteins
      (albumin, IgG, antitrypsin, IgA, transferrin and haptoglobin) allowed for the
      detection of 73 differentially expressed protein spots (n = 13, p < 0.01), of
      which 37 could be identified by mass spectrometry. These 37 spots comprised a
      total of 14 proteins, as follows: 7 had increased expression in plasmas from
      dengue fever patients (C1 inhibitor, alpha1-antichymotrypsin, vitamin D-binding
      protein, fibrinogen gamma-chain, alpha1-acid glycoprotein, apolipoprotein J and
      complement component C3c), while 7 others had decreased expression in the same
      samples (alpha-2 macroglobulin, prothrombin, histidine-rich glycoprotein,
      apolipoproteins A-IV and A-I, transthyretin and complement component C3b). The
      possible involvement of these proteins in the inflammatory process triggered by
      dengue virus infection and in the repair mechanisms of vascular damage occurring
      in this pathology is discussed in this study.

PMID- 19845403
TI  - Metabolic profiling of rat brain and cognitive behavioral tasks: potential
      complementary strategies in preclinical cognition enhancement research.
AB  - In this study, the correlation between the metabolic profiles of rats undergoing
      cognition enhancement drug therapy and their associated cognitive behavioral
      outcomes were investigated. Male Lister Hooded rats were administered either with
      donepezil, galantamine, or vehicle and subjected to Atlantis watermaze training
      and novel object recognition tests. An UPLC/MS/MS method was developed to profile
      21 neurologically related metabolites in the rat brains. Pharmacologically
      induced behavioral changes were compared subsequently with the metabolic
      fluctuations of neurologically related metabolites from multiple neurotransmitter
      pathways using multivariate and univariate statistical analyses. Significant
      improvements in cognitive behavioral outcomes were demonstrated in the rats
      administered with donepezil and galantamine using both AWM training (P < 0.05)
      and NOR (P < 0.05) tests as compared to those dosed with the vehicle. This
      corroborated with the significant elevation of eight prominent biomarkers after
      the cognitive enhancement therapy. An orthogonal partial least-squares
      discriminant analysis model generated using only the 8 metabolites identified as
      discriminating the drug-dosed rats from the vehicle-dosed rats gave a Q(2) =
      0.566, receiver operator characteristic (ROC) AUC = 1.000, using 7-fold cross
      validation. Our study suggests that metabolic profiling of rat brain is a
      potential complementary strategy to the cognitive behavioral tasks for
      characterizing neurobiological responses to cognition enhancement drug testing.

PMID- 19845404
TI  - Thermotropic phase behavior of trialkyl cyclohexanetriamides.
AB  - The thermotropic phase behavior of symmetric cyclohexanetriamides carrying
      various linear and branched alkyl chains was investigated using calorimetry,
      microscopy, solid-state NMR, dielectric relaxation spectroscopy, and X-ray
      scattering techniques. Cyclohexanetriamides carrying C(6) or longer linear alkyl
      chains formed columnar plastic phases with a pseudocentered rectangular lattice.
      Those with C(8) or longer alkyl chain also showed a nematic liquid crystalline
      phase. Cyclohexanetriamides carrying branched octyl chains displayed columnar
      phases with rectangular lattices, except for the triamide with the highly
      branched tetramethylbutyl group. The occurrence of less symmetrical columnar
      phases is ascribed to the mode of stacking of cyclohexanetriamides which leads to
      noncylindrical columns. Dielectric relaxation spectra also featured highly
      cooperative relaxation processes related to reorientation of the macrodipolar
      columns in the mesophase, showing the potential of these molecules as building
      blocks in responsive materials.

PMID- 19845405
TI  - Molecular dynamics of ethylene glycol dimethacrylate glass former: influence of
      different crystallization pathways.
AB  - The crystallization induced by different thermal treatments of a low molecular
      weight glass former, ethylene glycol dimethacrylate (EGDMA), was investigated by
      dielectric relaxation spectroscopy (DRS) and differential scanning calorimetry
      (DSC). The fully amorphous material, dielectrically characterized for the first
      time, exhibits three relaxation processes: the alpha-relaxation related to
      dynamic glass transition whose relaxation rate obeys a Vogel-Fulcher-Tamman-Hesse
      (VFTH) law and two secondary processes (beta and gamma) with Arrhenius
      temperature dependence. Therefore, the evaluation of distinct crystallization
      pathways driven by different thermal histories was accomplished by monitoring the
      mobility changes in the multiple dielectric relaxation processes. Besides
      isothermal cold-crystallization, nonisothermal crystallizations coming from both
      the melt and the glassy states were induced. While an amorphous fraction,
      characterized by a glass transition, remains subsequent to crystallization from
      the melt, no alpha-relaxation is detected after the material undergoes
      nonisothermal cold-crystallization. In the latter, the secondary relaxations
      persist with a new process that evolves at low frequencies, designated as alpha'
      that was also detected at advanced crystallization states under isothermal cold
      crystallization. Under the depletion of the alpha-relaxation, the beta-process
      when detected becomes better resolved keeping the same location prior to
      crystallization leading to a decoupled temperature dependence relative to the
      alpha-process.

PMID- 19845407
TI  - Properties of the diffuse double layer at high electrolyte concentrations.
AB  - The equations necessary to calculate the potential drop across the diffuse layer
      and its differential capacity are derived for 1:1 electrolytes on the basis of
      the Eigen and Wicke theory for concentrated electrolyte solutions. The results of
      this model are then compared with Monte Carlo data for more concentrated
      solutions and solutions with ions of large diameters. It is shown that the Eigen
      Wicke model is inadequate because it fails to consider the change in potential at
      a given ion due to its surrounding atmosphere.

PMID- 19845406
TI  - Langmuir monolayer study toward combined antileishmanian therapy involving
      amphotericin B and edelfosine.
AB  - In this work, the results of comparative studies on the effect of
      lysophospholipid analogue, edelfosine (ED), and its mixtures with the polyene
      antibiotic, amphotericin B (AmB), on model erythrocyte and parasite membranes are
      presented. Both compounds are known for their antileishmanian activity; however,
      the application of AmB is limited by its toxicity, while the treatment with alkyl
      lysophospholipids (edelfosine) is expensive in addition to its lower therapeutic
      activity as compared to the polyene. An additional problem is the emergence of
      resistance to both groups of drugs. The foregoing facts inspired the
      investigations toward combined amphotericin B/alkyl-lysophospholipid therapy. In
      this aspect, the effect of edelfosine on model erythrocyte versus parasite
      membrane has been verified by the incorporation of the drug into binary
      sterol/phospholipid monolayer of the proportion corresponding to the respective
      cellular membrane. Afterward, amphotericin B/edelfosine mixtures of various
      proportions (1:9; 1:1, and 9:1) have been added into sterol/phospholipid model
      membranes in the concentration of 1, 5, and 10%. The interactions between
      amphotericin B and edelfosine in mixed monolayers have also been investigated.
      The obtained results indicate that differences in the organization of erythrocyte
      versus parasite membranes are of great importance for selectivity of edelfosine
      toward the parasite membrane. The mixtures of drugs practically do not modify the
      properties of model erythrocyte membrane; however, their incorporation in the
      parasite membrane is thermodynamically unfavorable and causes membrane
      destabilization. The strongest differences in the influence of drug mixtures on
      erythrocyte versus parasite model membrane occur for 1% content of 1:9 and 1:1
      AmB/edelfosine mixture. Moreover, when edelfosine is combined with amphotericin
      B, a decrease in edelfosine concentration needed to induce a similar effect on
      parasite membranes as edelfosine alone does is observed. As a consequence of
      strong interactions between edelfosine and amphotericin B, the decrease of the
      activity of their mixtures on model membranes was found.

PMID- 19845408
TI  - Docking flexible peptide to flexible protein by molecular dynamics using two
      implicit-solvent models: an evaluation in protein kinase and phosphatase systems.
AB  - Reliable prediction of protein-ligand docking pose requires proper account of
      induced fit effects. Treating both the ligand and the protein as flexible
      molecules is still challenging because many degrees of freedom are involved.
      Peptides are one type of ligand that are particularly difficult to study because
      of their extreme flexibility. In this study, we tested a molecular dynamics-based
      simulated-annealing cycling protocol in docking peptides to four protein kinases
      and two phosphatases using two implicit-solvent models: a distance-dependent
      dielectric model (epsilon(r) = 4r) and a version of the Generalized Born model
      termed GBMV. We found that the simpler epsilon(r) = 4r model identified docking
      pose better than the more expensive GBMV model. In addition, rescoring structures
      obtained from one implicit-solvent model with the other identified good docking
      poses for all six systems studied. Including protein energy in scoring also
      improved results.

PMID- 19845409
TI  - Coarse-grained model for mechanosensitive ion channels.
AB  - In this work, a coarse-grained model for a kind of membrane protein, the
      mechanosensitive channel of small conductance (MscS), is proposed. The basic
      structure of the MscS is preserved when the protein is coarse-grained. For the
      coarse-grained model, the channels show two different states, namely the open and
      closed states, depending on the model parameters. Under the same membrane
      tension, the state of the ion channel is found to be critically determined by the
      protein structure, especially the length of the transmembrane alpha-helix. It is
      also found that for the protein with certain size, the gating transition occurs
      when the membrane tension is applied, resembling in a real mechanosensitive
      channel.

PMID- 19845410
TI  - Self-assembly of peptide-porphyrin complexes leads to pH-dependent excitonic
      coupling.
AB  - Using absorbance, fluorescence, resonance light scattering, and circular
      dichroism spectroscopy, we studied the self-assembly of the anionic meso-tetra(4
      sulfonatophenyl)porphine (TPPS(4)(2-/4-)) and a cationic 22-residue polypeptide.
      We found that three TPPS(4)(2-/4-) molecules bind to the peptide, which contains
      nine lysine residues in the primary sequence. In acidic solutions, when the
      peptide is in the random-coil conformation, TPPS(4)(2-) bound to the peptide
      forms excitonically coupled J-aggregates. In pH 7.6 solutions, when the peptide
      secondary structure is partially alpha-helical, the porphyrin-to-peptide binding
      constants are approximately the same as in acidic solutions (approximately 3 x
      10(6) M(-1)), but excitonic interactions between the porphyrins are
      insignificant. The binding of TPPS(4)(2-/4-) to lysine-containing peptides is
      cooperative and can be described by the Hill model. Our results show that
      porphyrin binding can be used to change the secondary structure of peptide-based
      biomaterials. In addition, binding to peptides could be used to optimize
      porphyrin intermolecular electronic interactions (exciton coupling), which is
      relevant for the design of light-harvesting antennas for artificial
      photosynthesis.

PMID- 19845411
TI  - The effect of preanalytical factors on stability of the proteome and selected
      metabolites in cerebrospinal fluid (CSF).
AB  - To standardize the use of cerebrospinal fluid (CSF) for biomarker research, a set
      of stability studies have been performed on porcine samples to investigate the
      influence of common sample handling procedures on proteins, peptides, metabolites
      and free amino acids. This study focuses at the effect on proteins and peptides,
      analyzed by applying label-free quantitation using microfluidics nanoscale liquid
      chromatography coupled with quadrupole time-of-flight mass spectrometry (chipLC
      MS) as well as matrix-assisted laser desorption ionization Fourier transform ion
      cyclotron resonance mass spectrometry (MALDI-FT-ICR-MS) and Orbitrap LC-MS/MS to
      trypsin-digested CSF samples. The factors assessed were a 30 or 120 min time
      delay at room temperature before storage at -80 degrees C after the collection of
      CSF in order to mimic potential delays in the clinic (delayed storage), storage
      at 4 degrees C after trypsin digestion to mimic the time that samples remain in
      the cooled autosampler of the analyzer, and repeated freeze-thaw cycles to mimic
      storage and handling procedures in the laboratory. The delayed storage factor was
      also analyzed by gas chromatography mass spectrometry (GC-MS) and liquid
      chromatography mass spectrometry (LC-MS) for changes of metabolites and free
      amino acids, respectively. Our results show that repeated freeze/thawing
      introduced changes in transthyretin peptide levels. The trypsin digested samples
      left at 4 degrees C in the autosampler showed a time-dependent decrease of peak
      areas for peptides from prostaglandin D-synthase and serotransferrin. Delayed
      storage of CSF led to changes in prostaglandin D-synthase derived peptides as
      well as to increased levels of certain amino acids and metabolites. The changes
      of metabolites, amino acids and proteins in the delayed storage study appear to
      be related to remaining white blood cells. Our recommendations are to centrifuge
      CSF samples immediately after collection to remove white blood cells, aliquot,
      and then snap-freeze the supernatant in liquid nitrogen for storage at -80
      degrees C. Preferably samples should not be left in the autosampler for more than
      24 h and freeze/thaw cycles should be avoided if at all possible.

PMID- 19845412
TI  - Aggressive behaviour in adults with intellectual disability: defining the role of
      drug treatment.
AB  - A complex form of aggression, commonly expanded as 'aggressive challenging
      behaviour', is reported in one in four adults with intellectual disability and is
      often treated with antipsychotics, mood stabilizers and antidepressants.
      Psychological treatments, including anger and behavioural management, person
      centred planning and manipulation of the environment (nidotherapy), have also
      been used when available but to a lesser extent. In this article, the evidence
      for efficacy for each intervention is examined, with data from randomized
      controlled trials given primacy. Very little evidence, based on limited data, can
      be found for the interventions of anger and behavioural management and also for
      the atypical antipsychotic drug, risperidone; the data available on these
      interventions come primarily from studies conducted in children in whom the
      behaviour is part of the autistic spectrum. Antipsychotic drugs, particularly the
      atypical group, have been the most commonly used interventions in recent years,
      but a recent independent randomized trial showed no benefits for either
      risperidone or haloperidol compared with placebo, with some evidence of a better
      response to placebo than either active drug in the reduction of aggression. In
      the light of this uncertainty, the clinician must return to the task of
      collecting a careful history and mental state examination, including awareness of
      the setting in which the behaviour is shown, which will help with diagnosis and
      appropriate intervention. The choice of intervention should not be a casual one
      and is not likely to be chosen well if the clinician relies only on standard
      guidelines. The paucity of randomized trial evidence is preventing progress in
      the treatment of persistent aggressive behaviour. On present evidence, the use of
      drug treatment should be much more sparing and reserved for those patients who
      are putting themselves and others at particular risk as a consequence of their
      behaviour; such treatment should be regarded as temporary and as adjunctive to
      other forms of management. There is an urgent need for larger, randomized studies
      of psychological interventions, which at present appear to have a higher benefit
      risk ratio than drug treatment but that also have a poor evidence base. More care
      should be taken to avoid the term 'aggressive challenging behaviour' being used
      as a portmanteau diagnostic pseudonym when it merely represents a diverse
      oppositional repertoire of many aetiologies.

PMID- 19845413
TI  - Of mice and men: bridging the translational disconnect in CNS drug discovery.
AB  - The tremendous advances in transgene animal technology, especially in the area of
      Alzheimer's disease, have not resulted in a significantly better success rate for
      drugs entering clinical development. Despite substantial increases in research
      and development budgets, the number of approved drugs in general has not
      increased, leading to the so-called innovation gap. While animal models have been
      very useful in documenting the possible pathological mechanisms in many CNS
      diseases, they are not very predictive in the area of drug development. This
      paper reports on a number of under-appreciated fundamental differences between
      animal models and human patients in the context of drug discovery with special
      emphasis on Alzheimer's disease and schizophrenia, such as different affinities
      of the same drug for human versus rodent target subtypes and the absence of many
      functional genotypes in animal models. I also offer a number of possible
      solutions to bridge the translational disconnect and improve the predictability
      of preclinical models, such as more emphasis on good-quality translational
      studies, more pre-competitive information sharing and the embracing of multi
      target pharmacology strategies. Re-engineering the process for drug discovery and
      development, in a similar way to other more successful industries, is another
      possible but disrupting solution to the growing innovation gap. This includes the
      development of hybrid computational models, based upon documented preclinical
      physiology and pharmacology, but populated and validated with clinical data from
      actual patients.

PMID- 19845414
TI  - Adjustment disorder: epidemiology, diagnosis and treatment.
AB  - Adjustment disorder was introduced into the psychiatric classification systems
      almost 30 years ago, although the concept was recognized for many years before
      that. In DSM-IV, six subtypes are described based on the predominant symptoms,
      but no further diagnostic criteria are offered to assist the clinician. These are
      common conditions, especially in primary care and in consultation liaison
      psychiatry, where the prevalence ranges from 11% to 18% and from 10% to 35%,
      respectively. Yet they are under-researched, possibly due to the failure of some
      of the common diagnostic tools to allow for the diagnosis of adjustment disorder.
      Among the tools that incorporate adjustment disorder, the concordance between the
      clinical and interview diagnosis is very poor, with the diagnosis being made more
      commonly in clinical practice than the diagnostic tools allow for. Adjustment
      disorder is found in all cultures and in all age groups. The presence of a causal
      stressor is essential before a diagnosis of adjustment disorder can be made,
      while the symptoms vary and include those that are found in other common
      psychiatric disorders. It is also important to distinguish adjustment disorder
      from normal reactions to stressful events. Adjustment disorders are difficult to
      distinguish from normal responses to life's stressors, while the distinction from
      major depression also poses a classificatory conundrum since both are
      conceptually different. Adjustment disorder is a diagnosis based on the
      longitudinal course of symptoms in the context of a stressor, while a diagnosis
      of major depression is a cross-sectional one based on symptom numbers. Treatments
      consist mainly of brief interventions, while pharmacotherapy is limited to the
      symptomatic management of anxiety or insomnia. There are no robust studies
      demonstrating benefits from antidepressants. However, the number of studies of
      either type of intervention is very limited.

PMID- 19845415
TI  - Cholinergic functioning in stimulant addiction: implications for medications
      development.
AB  - Acetylcholine, the first neurotransmitter discovered, participates in many CNS
      functions, including sensory and motor processing, sleep, nociception, mood,
      stress response, attention, arousal, memory, motivation and reward. These diverse
      cholinergic effects are mediated by nicotinic- and muscarinic-type cholinergic
      receptors (nAChR and mAChR, respectively). The goal of this review is to
      synthesize a growing literature that supports the potential role of acetylcholine
      as a treatment target for stimulant addiction. Acetylcholine interacts with the
      dopaminergic reward system in the ventral tegmental area, nucleus accumbens and
      prefrontal cortex. In the ventral tegmental area, both nAChR and mAChR stimulate
      the dopaminergic system. In the nucleus accumbens, cholinergic interneurons
      integrate cortical and subcortical information related to reward. In the
      prefrontal cortex, the cholinergic system contributes to the cognitive aspects of
      addiction. Preclinical studies support a facilitative role of nicotinic receptor
      agonists in the development of stimulant addiction. In contrast, nonselective
      muscarinic receptor agonists seem to have an inhibitory role. In human studies,
      acetylcholinesterase inhibitors, which increase synaptic acetylcholine levels,
      have shown promise for the treatment of stimulant addiction. Further studies
      testing the efficacy of cholinergic medications for stimulant addiction are
      warranted.

PMID- 19845416
TI  - Epidemiology and management of anxiety in patients with bipolar disorder.
AB  - Epidemiological and clinical studies have reported a high prevalence of anxiety
      symptoms in bipolar disorder, either in manic or depressive episodes, although
      these symptoms do not always meet criteria for a specific anxiety disorder. In
      addition to anxiety symptoms, bipolar disorder frequently presents with co-morbid
      axis I conditions, with anxiety disorders being the most common co-morbidity.
      Therefore, the objective of this article is to review clinical and
      epidemiological studies that have investigated the association between bipolar
      disorder and anxiety. Available data on the efficacy of treatments for bipolar
      disorder and co-morbid anxiety disorders are also reviewed. Existing guidelines
      do recognize that co-morbid anxiety has a negative impact on the course and
      outcome of bipolar disorder; however, there have been very few double-blind,
      controlled trials examining the treatment response of patients with bipolar
      disorder and co-occurring anxiety disorders. There is some positive evidence for
      quetiapine, olanzapine in combination with fluoxetine or lithium, and lamotrigine
      with lithium, and negative evidence for risperidone. Other therapies used for
      bipolar disorder, including several mood stabilizers, antidepressants, atypical
      antipsychotics and benzodiazepines, have been shown to reduce anxiety symptoms,
      but specific data for their effects in patients with anxiety symptoms co-morbid
      with bipolar disorder are not available. The co-occurrence of anxiety and bipolar
      disorder has implications for diagnosis, clinical outcome, treatment and
      prognosis. Careful screening for co-morbid anxiety symptoms and disorders is
      warranted when diagnosing and treating patients with bipolar disorder.

PMID- 19845418
TI  - Experience with intravenous levetiracetam in status epilepticus: a retrospective
      case series.
AB  - BACKGROUND: Status epilepticus is a medical emergency associated with significant
      morbidity and mortality. OBJECTIVE: To report our experience with the use of
      intravenous (IV) levetiracetam in patients with status epilepticus who had not
      responded to IV benzodiazepines. METHODS: A retrospective review of the clinical
      charts of patients with status epilepticus who were treated with IV levetiracetam
      from July 2007 to July 2008 in our department was performed. Data on
      demographics, epileptic syndrome, aetiology, treatment dosage and adverse effects
      were analysed. IV levetiracetam was administered over a period of 15-30 minutes;
      each 500 mg of levetiracetam was diluted in 100 mL of normal saline. RESULTS:
      Thirty-four patients (19 men and 15 women, 11-90 years old) with status
      epilepticus were treated with IV levetiracetam. Six patients (18%) had primarily
      generalized status epilepticus and 28 (82%) had focal status epilepticus. The
      aetiologies were: vascular (47%), cryptogenic (24%), tumours (12%), metabolic
      (12%) and brain anoxia (6%). The indications for administering IV levetiracetam
      were: no response to IV phenytoin and/or IV valproic acid (53% of patients) or to
      avoid adverse effects, contraindications or potential interactions (47% of
      patients). The median loading dose of IV levetiracetam was 1000 mg and the
      maintenance dosage ranged from 500 to 1500 mg/12 hours (median 1000 mg/12 hours).
      Status epilepticus stopped in a clear temporal relationship with IV levetiracetam
      in 71% of patients. IV levetiracetam was especially effective in older patients
      with vascular status epilepticus, while cryptogenic status epilepticus, primarily
      generalized status epilepticus, previous therapy with IV phenytoin and/or
      valproic acid and status epilepticus due to brain anoxia were associated with a
      poor response. There were no serious adverse events documented in the patients'
      charts. CONCLUSIONS: While waiting for large, controlled studies, our data
      suggest that IV levetiracetam might be an alternative for the treatment of status
      epilepticus, especially in elderly patients with vascular status epilepticus and
      concomitant medical conditions.

PMID- 19845419
TI  - Bending the curve: effective steps to address long-term healthcare spending
      growth.

PMID- 19845417
TI  - Visual field loss in patients with refractory partial epilepsy treated with
      vigabatrin: final results from an open-label, observational, multicentre study.
AB  - BACKGROUND: Use of the antiepileptic drug vigabatrin is associated with an
      elevated risk of visual field loss. OBJECTIVE: To determine the frequency of, and
      risk factors for, vigabatrin-attributed visual field loss (VAVFL) in the setting
      of a large-scale, multinational, prospective, observational study. STUDY DESIGN:
      A comparative, open-label, parallel-group, multicentre study. SETTING: Hospital
      outpatient clinics at 46 centres in five countries. PATIENTS: 734 patients with
      refractory partial epilepsy, divided into three groups and stratified by age (8
      12 years; >12 years) and exposure to vigabatrin. Group I comprised patients
      treated with vigabatrin for > or =6 months. Group II comprised patients
      previously treated with vigabatrin for > or =6 months who had withdrawn from the
      drug for > or =6 months. Group III comprised patients never treated with
      vigabatrin. Patients underwent perimetry at either 4- or 6-month intervals, for
      up to 36 months. Visual field outcome was evaluated masked to drug exposure.
      INTERVENTION: Perimetry. MAIN OUTCOME MEASURE: The visual field outcome at each
      of four analysis points: (i) at enrolment (i.e. baseline, all patients); (ii) for
      patients exhibiting a conclusive outcome at the initial visual field examination;
      (iii) for patients exhibiting at least one conclusive outcome to the visual field
      examinations; and (iv) at the last conclusive outcome to the visual field
      examinations. RESULTS: Of the 734 patients, 524 yielded one or more conclusive
      visual field examinations. For Group I, the frequency of VAVFL at the last
      conclusive examination was 10/38 (26.3%) for those aged 8-12 years and 65/150
      (43.3%) for those aged >12 years. For Group II, the respective frequencies were
      7/47 (14.9%) and 37/151 (24.5%). One case resembling VAVFL was present amongst
      the 186 patients in Group III at the last conclusive examination. The frequency
      of VAVFL in Groups I and II combined was 20.0% for those aged 8-12 years and
      33.9% for those aged >12 years. VAVFL was associated with duration of vigabatrin
      therapy (odds ratio [OR] up to 15.2; 95% CI 4.4, 51.7), mean daily dose of
      vigabatrin (OR up to 26.4; 95% CI 2.4, 291.7) and male gender (OR 2.51; 95% CI
      1.5, 4.1). VAVFL was more frequently detected with static than with kinetic
      perimetry (OR up to 0.43; 95% CI 0.24, 0.75). CONCLUSIONS: Since the probability
      of VAVFL is positively associated with treatment duration, careful assessment of
      the risk-benefit ratio of continuing treatment with vigabatrin is recommended in
      patients currently receiving this drug. All patients continuing to receive
      vigabatrin should undergo visual field examination at least every 6 months for
      the duration of treatment. We recommend two-level (three-zone), gradient-adapted,
      suprathreshold static perimetry of the peripheral field together with threshold
      perimetry of the central field out to 30 degrees from fixation. The frequency of
      ophthalmological and perimetric examinations should be increased in the presence
      of VAVFL.

PMID- 19845420
TI  - Impact of compliance with proton pump inhibitors on NSAID treatment.
AB  - OBJECTIVE: To assess the impact of patient compliance with proton pump inhibitor
      (PPI) therapy on nonsteroidal anti-inflammatory drug (NSAID) treatment duration
      and upper-gastrointestinal (GI) complications in patients with gastroesophageal
      reflux disease (GERD). STUDY DESIGN: Retrospective cohort study. METHODS: Study
      subjects were GERD patients receiving cotherapy with a PPI and a cyclooxygenase-2
      selective (COX-2-selective) or nonselective NSAID. Patients compliant and
      noncompliant with PPI therapy were compared on NSAID treatment duration and
      incidence of upper-GI events. Kaplan-Meier analysis and a multivariate Cox
      proportional hazards model were used to compare durations of NSAID treatment,
      controlling for baseline characteristics. The incidences of GI events were
      compared using incidence rate and Poisson regression models. The analyses were
      conducted separately for patients taking COX-2-selective NSAIDs and those taking
      nonselective NSAIDs. RESULTS: In both patient groups taking a COX-2-selective
      agent (n = 12,562; 70.9% compliant) and nonselective NSAID (n = 17,487; 69.9%
      compliant), mean NSAID treatment duration was significantly longer (84.0 days and
      20.8 days longer, respectively) in PPI-compliant patients than in noncompliant
      patients. Compliance with PPI therapy was associated with a greater reduction in
      the incidence of GI events than noncompliance in both patients taking a COX-2
      selective NSAID (6-fold vs 5-fold; P = .026) and patients taking a nonselective
      NSAID (8-fold vs 6-fold; P = .002). CONCLUSIONS: In GERD patients receiving
      NSAIDs, those who were compliant with PPI therapy had a longer NSAID treatment
      duration and better GI tolerability than those who were noncompliant.

PMID- 19845421
TI  - Statin adherence and mortality in patients enrolled in a secondary prevention
      program.
AB  - OBJECTIVES: To determine statin adherence rates in patients enrolled in a
      cardiovascular secondary disease prevention program and to evaluate the impact of
      adherence on subsequent clinical events. METHODS: Patients who had an incident
      cardiac event between January 1, 2000, and December 31, 2005, and began statin
      therapy within 90 days of that event were identified and followed until death, a
      recurrent nonfatal cardiac event, or December 31, 2006. Analysis was conducted in
      2007 and 2008. Adherence was calculated using proportion of days covered (PDC),
      which was dichotomized into overall PDC >80% and PDC <or=80%. Cox proportional
      hazards models were used to assess the association between PDC and time to death
      from any cause and/or recurrent nonfatal events. RESULTS: There were 2201
      patients in the study. The overall PDC was 75.4% over 3 years. The risk of any
      cause death was lower in patients with a PDC >80% compared with those with a PDC
      <or=80% (adjusted hazard ratio [HR] = 0.44; 95% confidence interval [CI] = 0.30,
      0.64). There was no difference between groups in nonfatal cardiac events.
      Patients with a PDC >80% had decreased risk of the combined outcome of death or
      nonfatal recurrent cardiac event compared with those with a PDC <or=80% (HR =
      0.75; 95% CI = 0.61, 0.93). CONCLUSION: Although our adherence rates were higher
      than those previously reported in the literature, statin nonadherence still is
      associated with higher mortality, demonstrating the need to continue to improve
      statin adherence in this population.

PMID- 19845422
TI  - VA pharmacy users: how they differ from other veterans.
AB  - OBJECTIVE: To compare users and nonusers of Veterans Affairs (VA) pharmacy
      services by age group. STUDY DESIGN: Cross-sectional. METHODS: We used data on
      sociodemographics, health status, and medical conditions from the Medical
      Expenditure Panel Survey (MEPS) to compare users and nonusers of VA pharmacies
      for medications. Data were pooled for 2003-2005 to ensure adequate sample sizes.
      Student t tests were used to compare the means for each variable, and all
      analyses were adjusted for the complex sample design of the MEPS. RESULTS: Among
      both nonelderly (18-64 years) and elderly (>or=65 years) veterans, a higher
      proportion who used VA pharmacy services versus those who did not use VA pharmacy
      services (1) were black (nonelderly: 17.7 % vs 7.4%, P <.001; elderly: 9.4% vs
      4.7%, P <.001); (2) had no alternative insurance (nonelderly: 27.2% vs 4.8%, P
      <.001; elderly: 36.3% vs 19.9%, P <.001); (3) had lower incomes (nonelderly:
      32.4% vs 11.5%, P <.001; elderly: 32.4% vs 25.4%, P = .01); (4) had less than a
      high school education (nonelderly: 13.0% vs 6.5%, P <.001; elderly: 27.5% vs
      17.6%, P <.001); (5) were disabled; and (6) reported poorer health. A higher
      percentage of nonelderly users reported a mental health condition (31.6% vs
      19.4%, P <.001). CONCLUSIONS: Veterans who use VA pharmacy services appear to be
      more ill than those who do not use VA pharmacy services. In addition, the VA
      appears to be a safety net for uninsured veterans who have mental health
      problems.

PMID- 19845423
TI  - Do patients continue to see physicians who are removed from a PPO network?
AB  - OBJECTIVES: To assess the extent to which excluding physicians from a preferred
      provider organization (PPO) network causes patients to discontinue using their
      services and whether the associated changes will result in greater demand for
      emergency department or inpatient care. STUDY DESIGN: Analysis of a natural
      experiment involving the narrowing of a PPO network operated by the Taft-Hartley
      Fund. The panel data analysis compared rates of patient discontinuation for
      excluded physicians before and after the change. The pre-post analysis used
      matched comparison groups for office visits, emergency department visits,
      inpatient admissions, and spending for affected patients. METHODS: Claims data
      analysis used generalized estimating equations and controlled for patient age,
      sex, health status, and hourly wage. Models examining utilization and spending
      for 6187 patients who remained with excluded physicians also used a propensity
      score-matched comparison group identified from among patients who had never seen
      an excluded physician. Differential response to physician exclusion according to
      age, health status, and hourly wage was also examined through interaction terms.
      RESULTS: The network narrowing reduced the odds of continuing to see an excluded
      physician (odds ratio, 0.18; P <.001). Patients who continued to see excluded
      physicians reduced their office visits by a mean of 0.9 visits per year, 0.8
      visits more than comparison patients (P <.001). There were no significant changes
      in emergency department visits or admissions for patients of excluded physicians
      compared with a matched cohort. CONCLUSIONS: Substantial copayment differentials
      may be an effective means of encouraging patients to change physicians. Where
      they are based on reliable information about provider quality and cost, tiered
      networks may improve value.

PMID- 19845425
TI  - The effect of certificate-of-need laws on hospital beds and healthcare
      expenditures: an empirical analysis.
AB  - OBJECTIVE: To estimate the effect of certificate-of-need legislation on hospital
      bed supply and healthcare expenditures. STUDY DESIGN: This study uses state data
      on several variables, including healthcare expenditures, hospital bed supply, and
      the existence of a certificate-of-need program, from 4 periods (1985, 1990, 1995,
      and 2000). METHODS: We estimate 2 multivariate regression equations. In the first
      equation, hospital bed supply is the dependent variable, and certificate of need
      is included as an independent variable. In the second equation, healthcare
      expenditures is the dependent variable, and hospital bed supply and certificate
      of need are included as independent variables. RESULTS: Certificate-of-need laws
      have reduced the number of hospital beds by about 10% and have reduced healthcare
      expenditures by almost 2%. Certificate-of-need programs did not have a direct
      effect on healthcare expenditures. CONCLUSION: Certificate-of-need programs have
      limited the growth in the supply of hospital beds, and this has led to a slight
      reduction in the growth of healthcare expenditures.

PMID- 19845424
TI  - Dental care coverage transitions.
AB  - OBJECTIVE: To examine dental insurance transition dynamics in the context of
      changing employment and retirement status. STUDY DESIGN: Data from the Health and
      Retirement Study (HRS) were analyzed for individuals 51 years and older between
      the 2004 and 2006 waves of the HRS. METHODS: The primary focus of the analysis is
      the relationship between retirement and transitions in dental care coverage. We
      calculate and present bivariate relationships between dental coverage and
      retirement status transitions over time and estimate a multivariable model of
      dental coverage controlling for retirement and other potentially confounding
      covariates. RESULTS: Older adults are likely to lose their dental coverage on
      entering retirement compared with those who remain in the labor force between
      waves of the HRS. While more than half of those persons in the youngest group (51
      64 years) were covered over this entire period, two-thirds of those in the oldest
      group (>or=75 years) were without coverage over the same period. We observe a
      high percentage of older persons flowing into and out of dental coverage over the
      period of our study, similar to flows into and out of poverty. CONCLUSIONS:
      Dental insurance is an important factor in the decision to seek dental care. Yet,
      no dental coverage is provided by Medicare, which provides medical insurance for
      almost all Americans 65 years and older. This loss of coverage could lead to
      distortions in the timing of when to seek care, ultimately leading to worse oral
      and overall health.

PMID- 19845426
TI  - Healthcare reform with a safety net: lessons from San Francisco.
AB  - Public hospital safety net systems face constant financial constraints, hindering
      their ability to provide adequate healthcare services. Many healthcare reform
      proposals would further weaken these systems by redirecting current safety net
      resources toward private insurance. Despite or perhaps because of this
      challenging environment, many successes in improving care for poor and vulnerable
      populations have been pioneered in safety net systems. San Francisco, California,
      is implementing several innovative programs to strengthen the financial viability
      of its healthcare safety net while also attempting to improve the access to and
      the quality of healthcare services.

PMID- 19845427
TI  - Delivering vaccines: a case study of the distribution system of Vaccines for
      Children.
AB  - OBJECTIVE: To evaluate the efficacy of the centralization by the Centers for
      Disease Control and Prevention of their pediatric vaccine distribution system.
      STUDY DESIGN: In March 2007, the Centers for Disease Control and Prevention began
      a pilot program to reform the Vaccines for Children (VFC) program. All California
      VFC providers were required to place vaccine orders under the centralized
      logistic system of the Vaccine Management Business Improvement Project (VMBIP).
      For this study, VFC ordering, use, and delivery data were collected from 2 large
      southern California healthcare providers that collectively served more than
      200,000 children. Data collection occurred between January 2005 and June 2008.
      METHODS: This case study measures the change in the mean VFC delivery times
      before and after the VMBIP. The data underwent simulation to estimate the number
      of days per year a provider would have zero VFC inventory before and after the
      VMBIP. RESULTS: After the VMBIP was implemented, delivery times increased from
      1.6 to 12.3 business days (P <.001). The probability that VFC deliveries took
      longer than 1 week increased from 7% before the VMBIP to 89% afterward. Our
      simulation demonstrates that for 7 of 11 vaccines investigated there was a
      statistically significant increase in the number of days a provider would be
      without VFC (P <.01). CONCLUSION: Although the VMBIP was implemented to save
      costs, this study finds that during the VMBIP's initial implementation timeline,
      providers experienced longer delivery delays and a higher probability of a VFC
      stockout.

PMID- 19845428
TI  - Office manager and nurse perspectives on facilitators of adult immunization.
AB  - OBJECTIVE: To assess which characteristics of primary care practices serving low-
      to middle-income white and minority patients relate to pneumococcal
      polysaccharide vaccine (PPV) and influenza vaccination rates. METHODS: In an
      intentional sample of 18 primary care practices, PPV and influenza vaccination
      rates were determined for a sample of 2289 patients >or=65 years old using
      medical record review. Office managers and lead nurses were surveyed about their
      office systems for providing adult immunizations, beliefs about PPV and influenza
      vaccines, and their own vaccination status. Hierarchical linear modeling (HLM)
      analyses were used to account for the clustered nature of the data. RESULTS:
      Sampled patients were most frequently female (61%) and white (83%), and averaged
      76 years of age. Weighted vaccination rates were 61.1% for PPV and 52.5% for
      influenza; rates varied by practice. Using HLM, with patient age and race entered
      as level 1 variables and office factors entered as level 2 variables, time
      allotted for an annual well visit was associated with a higher likelihood of
      influenza vaccination (odds ratio [OR] = 1.04; 95% confidence interval [CI] =
      1.02, 1.07; P = .003). Nurse influenza vaccination status was associated with a
      higher likelihood of PPV vaccination (OR = 3.81; 95% CI = 1.49, 9.78; P = .009).
      CONCLUSIONS: In addition to race and age, visit length and the nurses'
      vaccination status were associated with adult vaccination rates. Quality
      improvement initiatives for adult vaccination might include strengthening social
      influence of providers and/or ensuring that adequate time is scheduled for
      preventive care.

PMID- 19845429
TI  - Takashi Iyanagi: UGT1 gene complex: from Gunn rat to human.
AB  - UDP-glucuronosyltransferases (UGT) comprise a large gene superfamily that can be
      classified, based on the degree of amino-acid similarity between isoforms, into
      several gene families. Among these gene families, the UDP-glucuronosyltransferase
      family 1 (UGT1) gene is a unique gene complex organized to generate enzymes that
      share a common carboxyl terminal portion and are unique in the variable amino
      terminal region. Each variable exon I is preceded by a regulatory 5'-region and,
      in response to a specific signal, transcription processing splices mRNA from each
      unique exon 1 to the four common exons ( 2, 3, 4, and 5) to provide a template
      for synthesis of the individual isoforms. A novel clue to elucidate the gene
      structure of mammalian UGT1 was cDNA cloning of rat UGT1A6 from the
      hyperbilirubinemic Gunn rat by Professor Takashi Iyanagi Ph.D. The elucidation of
      the structure of the rat UGT1 gene complex has led to a greater understanding of
      the genetic basis of Crigler-Najjar and Gilbert's syndromes. Now, examination of
      the UGT1 gene structure in hyperbilirubinemic patients has revealed more than 100
      different genetic defects in Crigler-Najjar syndromes and one genetic alternation
      that accounts for the majority of Gilbert's syndrome cases. This review of a
      chapter in UGT history will focus on the extensive research of Iyanagi and
      coworkers with the rat UGT1 gene complex and advancing to the study of the human
      gene.

PMID- 19845430
TI  - Deactivation of anti-cancer drug letrozole to a carbinol metabolite by
      polymorphic cytochrome P450 2A6 in human liver microsomes.
AB  - Cytochromes P450 (P450) involved in letrozole metabolism were investigated. Among
      13 recombinant P450 forms examined, only P450 2A6 and 3A4 showed activities in
      transforming letrozole to its carbinol metabolite with small K(m) and high Vmax
      values yielding apparent Vmax/K(m) values of 0.48 and 0.24 nl min(-1) nmol(-1)
      P450, respectively. The metabolic activities of individual human liver microsomes
      showed a significant correlation with coumarin 7-hydroxylase activities (P450 2A6
      marker) at a letrozole concentration of 0.5 microM, while a good correlation was
      also seen with testosterone 6beta-hydroxylase activities (P450 3A4 marker) at 5
      microM substrate concentration with different inhibition by 8-methoxypsolaren.
      Significantly low carbinol-forming activities were seen in human liver microsomes
      from individuals possessing CYP2A6*4/*4 (whole CYP2A6 gene deletion) at a
      letrozole concentration of 0.5 microM. A Vmax/K(m) value measured for CYP2A6.7
      (amino acid substitution type) in human liver microsomes, in the presence of anti
      P450 3A4 antibodies, was approximately seven-fold smaller than that for CYP2A6.1
      (wild-type). These results demonstrate that P450 2A6 and 3A4 catalyse the
      conversion of letrozole to its carbinol metabolite in vitro at low and high
      concentrations of letrozole. Polymorphic variation of CYP2A6 is considered to be
      relevant to inter-subject variation in therapeutic exposure of letrozole.

PMID- 19845431
TI  - In vitro model for the prediction of clinical CYP3A4 induction using HepaRG
      cells.
AB  - It is important to predict CYP3A enzyme induction in the drug-discovery process
      to avoid adverse effects in clinical. In the present study, we constructed a
      method to correct the variability of in vitro CYP3A induction assays and thereby
      a method for the prediction of CYP3A induction in the clinical setting. Induction
      assays were performed in vitro using HepaRG cells and seven typical inducers. An
      index value was determined for enzyme induction, termed the relative factor (RF),
      from the ratio of the concentration of the inducers to the reference standards.
      Using RF as an index, variation among the assays was reduced. A good relationship
      was obtained between the ratio of the free plasma concentration at steady-state
      (C(ss,u)) to RF (expressed as C(ss,u)/RF) and the in vivo induction response.
      Using rifampicin as a reference standard, compounds with a C(ss,u)/RF value
      greater than 7.31 nmol l(-1) may induce CYP3A in vivo in humans.

PMID- 19845432
TI  - Metabolite screening of aromatic amine hair dyes using in vitro hepatic models.
AB  - Aromatic amines and heterocyclic amines are widely used ingredients in permanent
      hair dyes. However, little has been published on their potential for oxidation
      via hepatic cytochrome P450s. Therefore, the authors screened nine such compounds
      for their potential to undergo oxidative metabolism in human liver microsomes.
      Toluene-2,5-diamine (TDA), p-aminophenol, m-aminophenol, p-methylaminophenol,
      N,N'-bis(2-hydroxyethyl)-p-phenylenediamine, and 1-hydroxyethyl-4,5
      diaminopyrazole showed no evidence of oxidative metabolism. Oxidized metabolites
      of 4-amino-2-hydroxytoluene (AHT), 2-methyl-5- hydroxyethylaminophenol (MHEAP),
      and phenyl methyl pyrazolone (PMP) were detected, but there was no evidence of
      beta-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent covalent
      binding to microsomal protein, suggesting that these are not reactive
      metabolites. Metabolism of AHT, MHEAP, PMP, and TDA was further studied in human
      hepatocytes. All these compounds underwent conjugation, but no oxidative
      metabolites were found. The results suggest that none of the hair dye ingredients
      tested showed evidence of hepatic metabolism to potentially biologically reactive
      oxidized metabolites.

PMID- 19845433
TI  - Studies on induction of lamotrigine metabolism in transgenic UGT1 mice.
AB  - A transgenic 'knock-in' mouse model expressing a human UGT1 locus (Tg-UGT1) was
      recently developed and validated. Although these animals express mouse UGT1A
      proteins, UGT1A4 is a pseudo-gene in mice. Therefore, Tg-UGT1 mice serve as a
      'humanized' UGT1A4 animal model. Lamotrigine (LTG) is primarily metabolized to
      its N-glucuronide (LTGG) by hUGT1A4. This investigation aimed at examining the
      impact of pregnane X receptor (PXR), constitutive androstane receptor (CAR) and
      peroxisome proliferator-activated receptor (PPAR) activators on LTG
      glucuronidation in vivo and in vitro. Tg-UGT1 mice were administered the inducers
      phenobarbital (CAR), pregnenolone-16alpha-carbonitrile (PXR), WY-14643 (PPAR
      alpha), ciglitazone (PPAR-gamma), or L-165041 (PPAR-beta), once daily for 3 or 4
      days. Thereafter, LTG was administered orally and blood samples were collected
      over 24 h. LTG was measured in blood and formation of LTGG was measured in pooled
      microsomes made from the livers of treated animals. A three-fold increase in in
      vivo LTG clearance was seen after phenobarbital administration. In microsomes
      prepared from phenobarbital-treated Tg-UGT1 animals, 13-fold higher CL(int)
      (Vmax/K(m)) value was observed as compared with the untreated transgenic mice. A
      trend toward induction of catalytic activity in vitro and in vivo was also
      observed following pregnenolone-16alpha-carbonitrile and WY-14643 treatment. This
      study demonstrates the successful application of Tg-UGT1 mice as a novel tool to
      study the impact of induction and regulation on metabolism of UGT1A4 substrates.

PMID- 19845434
TI  - Comparison of mechanism-based inhibition of human cytochrome P450 2C19 by
      ticlopidine, clopidogrel, and prasugrel.
AB  - Mechanism-based inhibition of CYP2C19 in human liver microsomes by the
      thienopyridine antiplatelet agents clopidogrel, prasugrel and their thiolactone
      metabolites was investigated by determining the time- and concentration-dependent
      inhibition of the activity of S-mephenytoin 4'-hydroxylase as typical CYP2C19
      activity and compared with ticlopidine and its metabolite. Clopidogrel was shown
      to be a mechanism-based inhibitor of CYP2C19 with the inactivation kinetic
      parameters, k(inact) and K(I), equal to 0.0557 min(-1) and 14.3 microM,
      respectively, as well as ticlopidine (0.0739 min(-1) and 3.32 microM,
      respectively). The thiolactone metabolite of ticlopidine and clopidogrel
      inhibited CYP2C19 only in a concentration-dependent manner. In contrast, neither
      prasugrel nor its thiolactone metabolite inhibited CYP2C19 at concentrations up
      to 100 microM. The oxidation of the thiophene moiety of clopidogrel to form their
      respective thiolactones was found to be the critical reaction that produces the
      chemically reactive metabolites which cause the mechanism-based inhibition of
      CYP2C19. Estimation of in vivo drug-drug interaction using in vitro parameters
      predicted clinically observed data. For clopidogrel, there was no increase in the
      area under the curve (AUC) at its clinical dose level as predicted by the in
      vitro parameters, and for ticlopidine the prediction agreed with the clinically
      observed AUC increase. In conclusion, clopidogrel is potent mechanism-based
      inhibitors of CYP2C19 as well as ticlopidine, whereas prasugrel did not
      inactivate CYP2C19. Administration of prasugrel would not cause a clinically
      relevant interaction with CYP2C19.

PMID- 19845435
TI  - Effect of bifendate on the pharmacokinetics of talinolol in healthy subjects.
AB  - To evaluate the effect of bifendate on the pharmacokinetics of talinolol, 16
      unrelated male healthy subjects were selected for this study. After repeated oral
      administration of placebo or bifendate (three times daily for 14 days), the
      plasma concentration of talinolol was measured by high-performance liquid
      chromatography-electrospray mass spectrometry. This study was carried out in a
      randomized, single-blinded, placebo-controlled, crossover manner. After the
      treatment of bifendate, the area under the curve (AUC(0-infinity)) was decreased
      significantly by 11.2% (90% confidence interval (CI), 7.3-12.4%; p = 0.001), and
      the Cmax value of talinolol was decreased by approximately 9.7% (90% CI, 5.5
      11.4%; p = 0.001). The oral clearance of talinolol was increased significantly by
      13.1% (90% CI, 8.0-14.4%; p = 0.001). The results suggest that the treatment of
      bifendate can decrease the plasma concentration of talinolol in healthy subjects.

PMID- 19845437
TI  - Pharmacokinetics and anti-inflammatory pharmacodynamics of prednisolone in
      cynomolgus monkey.
AB  - The purpose was to investigate whether the pharmacokinetics and pharmacodynamics
      of prednisolone in the non-human primate was an appropriate surrogate for man.
      After single intravenous doses of 0.03, 0.3, and 3 mg kg(-1), prednisolone
      demonstrated a dose-dependent clearance and volume of distribution. When
      corrected for concentration-dependent protein binding, the free clearance was
      linear at the tested dose levels. The protein binding-corrected volume of
      distribution was similar across doses. The serum half-life was estimated as being
      between 2 and 4 h. Prednisolone exhibits near complete inhibition of the
      cytokines TNF-alpha, IL-1beta, IL-6 and IL-8 with very similar IC50 estimates
      from 0.09 to 0.16 microg ml(-1) (from 0.24 to 0.44 microM). The monkey
      demonstrated a similar pharmacokinetics-pharmacodynamics profile of prednisolone
      when compared with man (from the literature).

PMID- 19845436
TI  - Preclinical assessment of the absorption, distribution, metabolism and excretion
      of GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4
      (methylsulfonyl)benzamide), an orally bioavailable systemic Hedgehog signalling
      pathway inhibitor.
AB  - GDC-0449 (2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4
      (methylsulfonyl)benzamide) is a potent, selective Hedgehog (Hh) signalling
      pathway inhibitor being developed for the treatment of various cancers. The in
      vivo clearance of GDC-0449 was estimated to be 23.0, 4.65, 0.338, and 19.3 ml
      min(-1) kg(-1) in mouse, rat, dog and monkeys, respectively. The volume of
      distribution ranged from 0.490 in rats to 1.68 l kg(-1) in mice. Oral
      bioavailability ranged from 13% in monkeys to 53% in dogs. Predicted human
      clearance using allometry was 0.096-0.649 ml min(-1) kg(-1) and the predicted
      volume of distribution was 0.766 l kg(-1). Protein binding was extensive with an
      unbound fraction less than or equal to 6%, and the blood-to-plasma partition
      ratio ranged from 0.6 to 0.8 in all species tested. GDC-0449 was metabolically
      stable in mouse, rat, dog and human hepatocytes and had a more rapid turnover in
      monkey hepatocytes. Proposed metabolites from exploratory metabolite
      identification in vitro (rat, dog and human liver microsomes) and in vivo (dog
      and rat urine) include three primary oxidative metabolites (M1-M3) and three
      sequential glucuronides (M4-M6). Oxidative metabolites identified in microsomes
      M1 and M3 were formed primarily by P4503A4/5 (M1) and P4502C9 (M3). GDC-0449 was
      not a potent inhibitor of P4501A2, P4502B6, P4502D6, and P4503A4/5 with IC50
      estimates greater than 20 microM. K(i)'s estimated for P4502C8, P4502C9 and
      P4502C19 and were 6.0, 5.4 and 24 microM, respectively. An evaluation with Simcyp
      suggests that GDC-0449 has a low potential of inhibiting P4502C8 and P4502C9.
      Furthermore, GDC-0449 (15 microM) was not a potent P-glycoprotein/ABCB1 inhibitor
      in MDR1-MDCK cells. Overall, GDC-0449 has an attractive preclinical profile and
      is currently in Phase II clinical trials.

PMID- 19845438
TI  - Separate evaluation of intestinal and hepatic metabolism of three benzodiazepines
      in rats with cannulated portal and jugular veins: comparison with the profile in
      non-cannulated mice.
AB  - Pharmacokinetic analyses of three kinds of benzodiazepines--midazolam (MDZ),
      triazolam (TRZ) and alprezolam (APZ)--were performed in rats with cannulated
      portal and jugular veins. Each drug was administered to the double-cannulated
      rats, and pharmacokinetic data for the parent drugs and their 1'- and 4
      hydroxylated metabolites were compared with those obtained in non-cannulated
      mice. In bioavailability, the drugs ranked APZ >> TRZ = MDZ in rats, and APZ >
      TRZ >> MDZ in mice, with the values for MDZ remarkably different between rats and
      mice (19% in rats versus 2.3% in mice). In contrast, hepatic availability (Fh)
      was similar (APZ > TRZ > MDZ) in both species. Highly significant relationships
      were found between the ratio of the area under the plasma concentration-time
      curve (AUC) for the parent drugs in portal blood (AUC(por)) to that in systemic
      blood (AUC(sys)) and Fh in rats and mice. The double-cannulated rat is useful for
      estimating the hepatic availability of drug candidates by determining the AUC
      values for the parent drugs in portal and systemic blood samples.

PMID- 19845439
TI  - Call for contributions to the new Methods section in Platelets.

PMID- 19845440
TI  - Platelet reactivity and nonresponse to dual antiplatelet therapy: a review.
AB  - Clopidogrel is a second-generation thienopyridine that irreversibly inhibits the
      P2Y(12) adenosine diphosphate (ADP) receptor on platelets, preventing platelet
      aggregation. As early as 2003, researchers have observed inter-patient
      variability in response to clopidogrel, leading to a multitude of studies
      investigating the phenomenon of "clopidogrel resistance," due to the possible
      link between clopidogrel resistance and in-stent thrombosis. However, due to
      differences in study methodology and the lack of a clear definition, there is
      confusion about what it means and its clinical implications. Literature searches
      were performed using the Web of Science Database. Keywords used to search for
      relevant literature included clopidogrel resistance. While several studies have
      shown associations between high platelet reactivity and a high incidence of
      adverse outcomes, the optimal level of platelet inhibition is unknown. Regardless
      of the term used to describe high platelet reactivity after treatment, evidence
      shows that this leads to adverse clinical outcomes. Future goals for research
      should be aimed at developing a standard method of measuring platelet function
      and investigating determinants of high platelet reactivity. Alternative treatment
      options for patients with high platelet reactivity in the face of dual
      antiplatelet therapy are currently being investigated.

PMID- 19845441
TI  - Biodistribution of liposome/DNA systems after subcutaneous and intraperitoneal
      inoculation.
AB  - In this work, we analyzed protein interaction, cell toxicity, and biodistribution
      of liposome formulation for further possible applications as DNA vehicles in gene
      therapy protocols. In relation to protein interaction, cationic liposomes showed
      the lowest protein interaction, but this parameter was incremented with DNA
      association. On the other hand, noncharged liposomes presented high protein
      interaction, but DNA association decreased this parameter. Protein interaction of
      polymeric liposomes did not change with DNA association. Cell toxicity of these
      three liposome formulations was low, cell death became present at concentrations
      higher than 0.5 mg/mL, and these concentrations were higher than those usually
      used in transfection assays. In the case of noncharged and polymeric liposomes,
      toxicity increased upon interaction with serum proteins. DNA/liposome-mediated
      tissue distribution was analyzed in Balb-c female mice. Results indicated that
      noncharged liposomes were able to deliver DNA to liver after intraperitoneal
      (i.p.) inoculation, while polymeric liposomes were able to deliver DNA to kidney
      by using the same inoculation route. Cationic liposomes were able to deliver DNA
      to a wide range of tissues by the i.p. route (e.g., liver, intestine, kidney, and
      blood). After subcutaneous inoculation, only cationic liposomes were able to
      deliver DNA to blood, but not the other two formulations within the detection
      limits of the method.

PMID- 19845442
TI  - Rooting prebiotic chirality in spinomeric chemistry?
AB  - Spinomeric chemistry is a domain of physical chemistry that explores the role of
      spin-isomery in chemical reactivity. In large magnetic fields (B), chemical
      structures with three adjacent nuclear spins (such as H(2)(17)O, H(2)(33)S,
      NH(2), and and -(13)CH(2)-) form complex spinomers. Known departure from a 1:1
      ratio between various types of spinomers opens interesting research avenues in
      their potential role in asymmetric hydration processes. Recent time domain (1)H
      nuclear magnetic resonance (TD-(1)HNMR) findings revealed the existence of small,
      yet consistent, H(2)(17)O-controlled enantio-different proton exchange reactivity
      in sugars. The mechanisms behind this effect are unclear and may involve
      spinomer/enantiocenter (e.g., H(2)(17)O/*C) interactions or spinomer/spinomer
      (e.g., H(2)(17)O/-NH(2)) interactions. We developed an experimental model that
      allows for the verification and study of such effects. We used TD-(1)HNMR at
      0.589 T to study and compare proton exchange enantio-differences in asparagine
      (Asn) and mandelic acid in response to titration with H(2)(17)O at constant pH.
      Unlike Asn, mandelic acid has no complex spinomer group (such as -NH(2)) in its
      chiral center. We report finding enantio-differences regarding DeltapK and
      1/T(2)(0) correlated with H(2)(17)O, and linear changes in DeltaM(2) indicating
      differences in the affinity of enantiomers for H(2)(17)O surface hydration. These
      results stress the importance of H(2)(17)O-based spinomeric chemistry in chiral
      reactivity and open windows toward a novel interpretation of the origin of
      prebiotic chiral reactivity in the presence of moderately large B (such as on
      magnetic mineral surfaces or on satellites of gaseous giants), as well as toward
      abiotic isotopic fractionation of H(2)(17)O in the presence of chiral organic
      molecules.

PMID- 19845443
TI  - Characterization of organics, microorganisms, desert soils, and Mars-like soils
      by thermal volatilization coupled to mass spectrometry and their implications for
      the search for organics on Mars by Phoenix and future space missions.
AB  - A key goal for astrobiology is the search for evidence of life on Mars. Because
      liquid water is a fundamental environmental requirement for life, the recent set
      of missions to Mars have focused on a strategy known as "follow the water." Since
      life is made of organic molecules, a logical next step is "follow the organics."
      However, organics are expected to be present at very low levels on Mars, which
      would make their detection challenging. Viking was unable to detect organics at
      parts per billion (ppb), but the effective upper limit could be higher due to the
      low efficiency of the thermal volatilization (TV) step in releasing organics. Due
      to its ease of use, TV is still the method selected for current and future NASA
      and ESA missions. Here, we show that when organics are present in the soil at
      levels above 1500 parts per million (ppm), there are several characteristic
      organic fragments detected by TV-mass spectrometry; however, when the levels are
      below <150 ppm, TV oxidizes them, and no organic fragments are released. Instead,
      nitric oxide (NO) is produced and can be used to determine quantitatively the
      organic content if the C/N ratio is determined. Any atmospheric NO sorbed or
      mineral nitrogen (e.g., nitrates) present in the soil would release NO by TV at
      distinctive temperature regimes that would not overlap with the organic nitrogen
      source. Therefore, we suggest that monitoring NO provides the best chance for
      Phoenix and other future Mars missions to detect nitrogen-containing organics in
      the soil or ice.

PMID- 19845444
TI  - Survey on astrobiology research and teaching activities within the United
      kingdom.
AB  - While astrobiology is apparently growing steadily around the world, in terms of
      the number of researchers drawn into this interdisciplinary area and teaching
      courses provided for new students, there have been very few studies conducted to
      chart this expansion quantitatively. To address this deficiency, the Astrobiology
      Society of Britain (ASB) conducted a questionnaire survey of universities and
      research institutions nationwide to ascertain the current extent of astrobiology
      research and teaching in the UK. The aim was to provide compiled statistics and
      an information resource for those who seek research groups or courses of study,
      and to facilitate new interdisciplinary collaborations. The report here
      summarizes details gathered on 33 UK research groups, which involved 286
      researchers (from undergraduate project students to faculty members). The survey
      indicates that around 880 students are taking university-level courses, with
      significant elements of astrobiology included, every year in the UK. Data are
      also presented on the composition of astrobiology students by their original
      academic field, which show a significant dominance of physics and astronomy
      students. This survey represents the first published systematic national
      assessment of astrobiological academic activity and indicates that this emerging
      field has already achieved a strong degree of penetration into the UK academic
      community.

PMID- 19845445
TI  - Thermally altered Silurian cyanobacterial mats: a key to Earth's oldest fossils.
AB  - Diagenetic changes in thermally altered cyanobacterial mats from early Silurian
      black radiolarian cherts of southwestern Poland (Bardzkie Montains, Sudetes) have
      been studied. These early diagenetically silicified mats are composed of
      variously degraded remains of benthic microbes that resemble some modern
      chroococcalean and pleurocapsalean cyanobacteria. Two modes of degradational
      processes have been recognized in the studied mats: (i) early postmortem
      biodegradation and (ii) late diagenetic thermal or thermobaric degradation. The
      latter led to partial transformation of the fossilized organic remnants of
      cyanobacterial sheaths and capsules, which resulted in the formation of objects
      morphologically distant from the original microbiota but preserved features that
      allow for their identification as bona fide biogenic structures. Some of these
      thermally generated Silurian fossils are highly similar to the controversial
      microfossil-like carbonaceous structures described from the Early Archean Apex
      Chert of Australia. This similarity opens a promising way for credible
      recognition of remnants of cyanobacteria and similar microbiota in other
      thermally metamorphosed Archean sedimentary rocks.

PMID- 19845446
TI  - Planning considerations for a Mars Sample Receiving Facility: summary and
      interpretation of three design studies.
AB  - It has been widely understood for many years that an essential component of a
      Mars Sample Return mission is a Sample Receiving Facility (SRF). The purpose of
      such a facility would be to take delivery of the flight hardware that lands on
      Earth, open the spacecraft and extract the sample container and samples, and
      conduct an agreed-upon test protocol, while ensuring strict containment and
      contamination control of the samples while in the SRF. Any samples that are found
      to be non-hazardous (or are rendered non-hazardous by sterilization) would then
      be transferred to long-term curation. Although the general concept of an SRF is
      relatively straightforward, there has been considerable discussion about
      implementation planning. The Mars Exploration Program carried out an analysis of
      the attributes of an SRF to establish its scope, including minimum size and
      functionality, budgetary requirements (capital cost, operating costs, cost
      profile), and development schedule. The approach was to arrange for three
      independent design studies, each led by an architectural design firm, and compare
      the results. While there were many design elements in common identified by each
      study team, there were significant differences in the way human operators were to
      interact with the systems. In aggregate, the design studies provided insight into
      the attributes of a future SRF and the complex factors to consider for future
      programmatic planning.

PMID- 19845447
TI  - Rapid culture-independent microbial analysis aboard the International Space
      Station (ISS).
AB  - A new culture-independent system for microbial monitoring, called the Lab-On-a
      Chip Application Development Portable Test System (LOCAD-PTS), was operated
      aboard the International Space Station (ISS). LOCAD-PTS was launched to the ISS
      aboard Space Shuttle STS-116 on December 9, 2006, and has since been used by ISS
      crews to monitor endotoxin on cabin surfaces. Quantitative analysis was performed
      within 15 minutes, and sample return to Earth was not required. Endotoxin (a
      marker of Gram-negative bacteria) was distributed throughout the ISS, despite
      previous indications that mostbacteria on ISS surfaces were Gram-positive
      [corrected].Endotoxin was detected at 24 out of 42 surface areas tested and at
      every surface site where colony-forming units (cfu) were observed, even at levels
      of 4-120 bacterial cfu per 100 cm(2), which is below NASA in-flight requirements
      (<10,000 bacterial cfu per 100 cm(2)). Absent to low levels of endotoxin (<0.24
      to 1.0 EU per 100 cm(2); defined in endotoxin units, or EU) were found on 31
      surface areas, including on most panels in Node 1 and the US Lab. High to
      moderate levels (1.01 to 14.7 EU per 100 cm(2)) were found on 11 surface areas,
      including at exercise, hygiene, sleeping, and dining facilities. Endotoxin was
      absent from airlock surfaces, except the Extravehicular Hatch Handle (>3.78 EU
      per 100 cm(2)). Based upon data collected from the ISS so far, new culture
      independent requirements (defined in EU) are suggested, which are verifiable in
      flight with LOCAD-PTS yet high enough to avoid false alarms. The suggested
      requirements are intended to supplement current ISS requirements (defined in cfu)
      and would serve a dual purpose of safeguarding crew health (internal spacecraft
      surfaces <20 EU per 100 cm(2)) and monitoring forward contamination during
      Constellation missions (surfaces periodically exposed to the external
      environment, including the airlock and space suits, <0.24 EU per 100 cm(2)).

PMID- 19845448
TI  - Microbial dissolution of hematite and associated cellular fossilization by
      reduced iron phases: a study of ancient microbe-mineral surface interactions.
AB  - We report here on magnetite- and wustite-encrusted and geometrically oriented
      microbial-like structures (MLS) attached to the surfaces of hematite (alpha
      Fe(2)O(3)) crystals in a banded iron formation. Field emission scanning electron
      microscope (FE-SEM) and scanning electron microscope (SEM) imaging showed a 3-D
      network of MLS arranged in 1 microm x approximately 20 microm coccoidal-like
      chains (CLC) of various geometrical shapes: dichotomous and budding-like
      protrusions, parallel, intersecting, triangular, or sinusoidal. Individual
      spheroidal forms ( approximately 1 mum in diameter), some displaying what appears
      to be division, were also abundant. In addition to their size, morphology, and
      preferred orientations, a microbial origin of these chains and single spheroidal
      forms is inferred by the presence of material that resembles extracellular
      polymeric substances (EPS) extending from the base of the chains along the
      mineral surface: the attachment sites show circular dissolution pits of about 100
      nm diameter. Other thin structures protruding from the CLC are reminiscent of
      bacterial "nanowires." We were, however, unable to find any extant cells, organic
      carbon, or even recover DNA from the MLS, which suggests that they, if microbial,
      are possibly mineralogically replaced casts or mineral encrustations of cells. It
      is further speculated that, given the nature of the substrate upon which the
      forms are attached and their preferential orientations, it seems plausible that
      the "original cells" may have been Fe(III)-reducing bacteria that exploited
      structural imperfections in the crystal lattice. Importantly, the preservation of
      the ancient microbial shapes in mineral casts of magnetite, wustite, or both may
      be an overlooked means by which cellular features in the rock record are
      retained.

PMID- 19845449
TI  - Bacillus thuringiensis conjugation in simulated microgravity.
AB  - Spaceflight experiments have suggested a possible effect of microgravity on the
      plasmid transfer among strains of the Gram-positive Bacillus thuringiensis, as
      opposed to no effect recorded for Gram-negative conjugation. To investigate these
      potential effects in a more affordable experimental setup, three ground-based
      microgravity simulators were tested: the Rotating Wall Vessel (RWV), the Random
      Positioning Machine (RPM), and a superconducting magnet. The bacterial
      conjugative system consisted in biparental matings between two B. thuringiensis
      strains, where the transfer frequencies of the conjugative plasmid pAW63 and its
      ability to mobilize the nonconjugative plasmid pUB110 were assessed.
      Specifically, potential plasmid transfers in a 0 g position (simulated
      microgravity) were compared to those obtained under 1 g (normal gravity)
      condition in each device. Statistical analyses revealed no significant difference
      in the conjugative and mobilizable transfer frequencies between the three
      different simulated microgravitational conditions and our standard laboratory
      condition. These important ground-based observations emphasize the fact that,
      though no stimulation of plasmid transfer was observed, no inhibition was
      observed either. In the case of Gram-positive bacteria, this ability to exchange
      plasmids in weightlessness, as occurs under Earth's conditions, should be seen as
      particularly relevant in the scope of spread of antibiotic resistances and
      bacterial virulence.

PMID- 19845450
TI  - Taste masking of Etoricoxib by using ion-exchange resin.
AB  - The present study was carried out in order to mask the bitter taste of the
      Etoricoxib by complexation with cation-exchange resin, Indion 204. The drug resin
      complexes (DRC) were prepared by batch process and efficient drug loading was
      obtained by using inactivated form of resin in the drug-resin ratio 1:3.3 with 30
      min swelling time of resin in 25 mL of water with 5 min stirring time. Drug-resin
      complexes were characterized for dissolution studies and spectral studies. Drug
      release from drug-resin complex in salivary pH was insufficient to impart bitter
      taste. Volunteers rated the drug resin complex as tasteless and agreeable.

PMID- 19845451
TI  - The effects of pregnancy on the exacerbation and development of maternal allergic
      respiratory disease.
AB  - The T-helper 2 (T(H)2) bias associated with pregnancy may predispose the pregnant
      mother to the development or exacerbation of allergic disease. To determine the
      effects of pregnancy on pre-existing maternal sensitization, we sensitized BALB/c
      mice before breeding by two intratracheal aspiration (IA) exposures to the fungal
      allergen, Metarhizium anisopliae crude antigen (MACA). Some mice also received
      three IA exposures to MACA on gestational days 11, 15, and 19. After weaning, all
      mice were challenged IA with MACA before killing. To determine the effects of
      pregnancy on susceptibility to future sensitization, naive parous and nulliparous
      BALB/c mice were sensitized by three IA exposures to MACA or to Hank's buffered
      salt solution vehicle control. Pregnancy did not have a significant effect on
      individual inflammatory parameters (airway responsiveness to methacholine, total
      serum and bronchoalveolar lavage fluid (BALF) IgE, BALF total protein, lactate
      dehydrogenase activity, and total and differential cell counts) following
      allergen challenge in sensitized mice, regardless of post-breeding allergen
      exposure. In conclusion there was a weak inhibition of the overall response in
      mice exposed to allergen during pregnancy compared to identically treated
      nulliparous mice. In contrast, parous mice that did not encounter allergen post
      breeding tended to have exacerbated responses. Parity had no significant impact
      on future susceptibility to sensitization.

PMID- 19845452
TI  - Altered plasma albumin characteristics and lymphocyte populations in
      gastrointestinal cancer patients: detection using modified fluorescence
      responses.
AB  - The fluorescent probe ABM (an amino derivative of benzanthrone) developed at Riga
      Technical University (Riga, Latvia) was used to characterize the blood plasma
      albumin of cancer patients (46 gastrointestinal cancer patients--30 with
      colorectal cancer in Stages II-IV and 16 with gastric cancer in Stage III) and of
      healthy controls. The fluorescence intensity of ABM in the blood plasma decreased
      from the control mean value and showed specific differences in the patients
      before (i.e., 24 hr pre-) and after (i.e., 10 day post-) they underwent a
      medically indicated surgical treatment, i.e., a gastric resection or gastroectomy
      for patients in the gastric cancer group or a colorectal resection for patients
      in the colorectum cancer group. The significant decrease in the ABM fluorescence
      in the blood plasma could be explained, in part, by a diminished binding capacity
      of the albumin of these patients. In fact, before surgery, there was a strong
      reduction in binding constant (K(a)) value for the probe observed in the plasma
      samples from these patients as compared with the value obtained with the plasma
      of the healthy donors. The lymphocyte distribution among the subsets also
      differed between the groups. Surgical treatment affected several immunological
      parameters and appeared to elevate the functional status of lymphocytes.
      Interestingly, the ABM fluorescence in the blood plasma was also seen to
      correlate with select immunological parameters (CD4+:CD8+ ratios, levels of CD38+
      cells, etc.) both before and after the patients' operations. The results in the
      present study suggest that measures of ABM fluorescence intensity values for
      plasma albumin and/or especially of lymphocytes (as reflections of their
      functional activity) might be a useful tool in the evaluation of the immune
      status of gastrointestinal cancer patients.

PMID- 19845453
TI  - Effects of persistent CO(2) insufflation during different laparoscopic inguinal
      hernioplasty: a prospective, randomized, controlled study.
AB  - OBJECTIVE: The aims of this study were to investigate the effects of carbon
      dioxide (CO(2)) insufflation on hemodynamic and respiratory function during
      laparoscopic inguinal hernioplasty and to evaluate the safety of transabdominal
      preperitoneal hernia repair (TAPP) and extraperitoneal hernia repair (TEP).
      MATERIALS AND METHODS: Forty patients with inguinal hernia were admitted for
      laparoscopic inguinal hernia repair in our study. The patients were randomly
      assigned to undergo TAPP (TAPP group, n = 20) or TEP (TEP group, n = 20).
      Hemodynamic and respiratory parameters, including heart rate, blood pressure, end
      tidal CO(2) (EtCO(2)), and blood-gas parameters, were observed and compared
      between the two groups. RESULTS: There was no significant difference between the
      two groups in terms of sex, age, American Society of Anesthesiology degree, body
      mass index, type of hernia, operation time, hospital stay, and postoperative pain
      score. In both groups, 5 minutes into the operation, blood pressure, EtCO(2),
      PaCO(2), and HCO(3)(-) increased significantly, whereas heart rate and pH
      decreased significantly (P < 0.05). The above tendency became significant with
      the operation prolonged. All parameters recovered to normal levels at the end of
      surgery. No significant difference was found between the TAPP and TEP groups.
      CONCLUSIONS: Both TAPP and TEP procedures can result in CO(2) accumulation,
      acidosis, increased blood pressure, and decreased heart rate. But, these effects
      were transient and could be well controlled by appropriate treatments during the
      operation. The laparoscopic TAPP and TEP techniques are safe for patients by
      proper perioperative management.

PMID- 19845454
TI  - Evaluation of a technical skills training program in surgical residents.
AB  - BACKGROUND: In recent years, the interest for training programs to teach
      technical skills has enormously grown. The aim of this study was to evaluate the
      influence of surgical training on the technical skills of surgical residents.
      METHODS: Forty residents participated in a training program consisting of 1
      training day followed by 6 weeks of autonomous training. Participants were asked
      to rate their confidence with the open and laparoscopic knot-tying technique by a
      visual analog scale before and after the training day (post), and after the
      period of autonomous training (follow-up). Objective assessment was performed
      according to the Objective Structured Assessment of Technical Skills. RESULTS:
      Mean (+ or - standard deviation) baseline confidence of participants with the
      open technique was 68.2 + or - 14.5, increased post to 76.4 + or - 13.2 (P <
      0.001), and was 77.8 + or - 9.6 at follow-up (not significant). Mean objective
      score was post increased from 19.2 + or - 3.5 to 21.4 + or - 3.4 (P = 0.001) but
      decreased to 20.2 + or - 4.1 at follow-up. For the laparoscopic technique, mean
      confidence increased from 20.6 + or - 14.4 to 47.2 + or - 19.0 post, and 62.7 +
      or - 14.0 at follow-up (P < 0.001 for both). Mean objective score was post
      increased from 22.1 + or - 8.2 to 34.9 + or - 6.4 (P = 0.001), which did not
      change at follow-up (33.3 + or - 7.5). CONCLUSIONS: In this study, confidence in
      the open knot-tying technique first increased after the initial training day and
      then stabilized, whereas the objective level initially improved, but returned to
      baseline level at follow-up. Regarding the laparoscopic technique, a significant
      increase of confidence after both the training and after 6 weeks of follow-up was
      observed. Improvement of the objective level after the training day was
      maintained at follow-up.

PMID- 19845455
TI  - Left inferior quadrant oblique incision: a new access for hand-assisted device
      during laparoscopic low anterior resection of rectal cancer.
AB  - BACKGROUND: Although long-term results are not clear, laparoscopic resection of
      rectal cancer may be feasible, and the use of hand-assisted technique may ease
      the procedure. This article aims to describe the details of left inferior
      quadrant oblique incision (LIQOI) and to discuss the results of patients who
      underwent laparoscopic hand-assisted low anterior resection using LIQOI.
      MATERIALS AND METHODS: All rectal cancer patients who underwent a hand-assisted
      low anterior resection through a LIQOI at our department between November 2006
      and May 2008 were retrospectively evaluated. The details of the procedures were
      assessed. RESULTS AND DISCUSSION: At the time of laparoscopic rectal cancer
      surgery, LIQOI was used on 23 patients (13 males; 56.5%) with a mean age of 55.2;
      standard deviation was 12.8 years. Conversion to open surgery was necessitated in
      1 patient (4.4%), who was suspected to have a T4 tumor, and another case (4.4%)
      with a severe cardiac illness died 7 days after surgery. The right and left hands
      were used to help the mobilization of splenic flexure and rectum, respectively,
      after the insertion of the hand-assisted device through LIQOI. CONCLUSION: This
      incision may allow the uncomplicated mobilization of splenic flexure and rectum
      and thus ease the hand-assisted low anterior resection procedure.

PMID- 19845456
TI  - What is the best treatment for ureteropelvic junction obstruction? In response
      to: ureteropelvic junction obstruction: which is the best treatment today?

PMID- 19845457
TI  - Program evaluation.

PMID- 19845458
TI  - Child care research: issues, perspectives, and results.

PMID- 19845459
TI  - Eco-evolutionary dynamics of mutualists and exploiters.
AB  - With the growing recognition of exploiters as a prominent and enduring feature of
      many mutualisms, there is a need to understand the ecological and evolutionary
      dynamics of mutualisms in the context of exploitation. Here, we model coevolution
      between mutualist and exploiter birth rates, using an obligate pollinating seed
      parasite mutualism associated with a nonpollinating exploiter as a reference
      system. In this system, mutualist and exploiter larvae parasitize the host plant,
      competing for and consuming seeds. Evolution of the mutualist determines which
      exploiters can invade successfully. Subsequent coevolution with an exploiter has
      a strong, predictable influence on mutualist-exploiter coexistence, mutualist and
      exploiter phenotypes, and species abundances. Weak mutualist competition promotes
      "evolutionary purging" of the exploiter, while weak exploiter competition leads
      to "evolutionary suicide" of the system. When stable, long-term coexistence
      occurs, we identify two main "trait-abundance syndromes" that have three novel
      implications. (1) Persistent, highly parasitic exploiters can be favored by
      coevolution. (2) Even then, the density of coevolved mutualists can be high. (3)
      Low plant density results primarily from the evolution of mutualist, not
      exploiter, birth rate and density. To evaluate these predictions, studies are
      needed that identify and compare populations with and without exploiters and
      compare life-history traits of mutualists and exploiters.

PMID- 19845460
TI  - Uniaxial strain regulates morphogenesis, gene expression, and tissue strength in
      engineered skin.
AB  - Mechanical properties of engineered tissues should ideally match those of the
      tissues that are replaced. Engineered skin (ES) is often orders of magnitude
      weaker than normal skin, which can lead to damage during application and improper
      function after engraftment. Hypothetically, application of strain during culture
      of ES may lead to improved mechanical properties. ES comprised of electrospun
      collagen scaffolds, human dermal fibroblasts, and epidermal keratinocytes were
      fabricated and cultured at the air-liquid interface. ES was loaded in vitro into
      a strain apparatus, strained to 0% (restrained), 5%, 10%, 20%, or 40%, with
      unstrained ES as a control, and cultured for 10 days. ES cultured under 10% and
      20% strain were significantly stronger than unstrained controls. ES cultured
      under 20% strain showed upregulation of many genes encoding structural
      extracellular matrix proteins, including collagen type I alpha 1 and fibronectin
      1. Mechanical stimulation significantly increased epidermal cell proliferation
      and enhanced epidermal differentiation with 5%, 10%, and 20% strain. Improved
      strength in the 10% and 20% strain groups is likely a result of increased
      extracellular matrix production coupled with enhanced epidermal differentiation.
      These improvements to ES may facilitate surgical application, prevent damage
      during transplantation, and may result in improved functional outcomes after
      engraftment.

PMID- 19845462
TI  - Tissue engineering of the anterior cruciate ligament-sodium dodecyl sulfate
      acellularized and revitalized tendons are inferior to native tendons.
AB  - The acellularization of tendons using detergents (sodium dodecyl sulfate, Triton
      X, tri-nitro-butyl-phosphate) is a new source of scaffolds for tissue engineering
      in anterior cruciate ligament (ACL) repair. In vitro testing demonstrated that
      acellular tendon scaffolds are biocompatible and show good biomechanical
      properties, but in vivo confirmation of these results is not yet available.
      Therefore, the aim of this study was to see in vivo if an acellular allogenic
      construct colonized with autologous fibroblasts improves the quality of ACL
      reconstruction. ACL replacement was performed in 31 New Zealand White rabbits
      using a standardized model. Fifteen animals received autologous semitendinosus
      tendon, whereas 16 animals were treated with a tissue-engineered construct. This
      construct was made by acellularization of allogenic semitendinosus tendons using
      sodium dodecyl sulfate and subsequent in vitro colonization with autologous
      fibroblasts. Eight weeks postoperatively, macroscopic, biomechanical (ultimate
      load to failure, elongation, stiffness; n = 8/9), and histological (n = 5)
      examinations were performed. Biomechanical testing showed decreasing strength of
      the constructs at 8 weeks after implantation compared with the direct
      postsurgical strength. However, tissue-engineered constructs (F = 19.7 +/- 20.3
      N) were significantly weaker than autologous tendons (F = 61.2 +/- 31.2 N).
      Histologically, the autologous tendons showed signs of partial necrosis and
      tissue remodeling. The tissue-engineered constructs exhibited an inflammatory
      reaction and showed both repopulated and acellular regions. In conclusion, in
      vivo results were much more unfavorable than in vitro results had suggested.
      Further studies have to be performed to test if modifications of the
      acellularization process yield better results in vivo.

PMID- 19845461
TI  - Maintenance of human hepatocyte function in vitro by liver-derived extracellular
      matrix gels.
AB  - Tissue engineering and regenerative medicine (TE&RM) approaches to treating liver
      disease have the potential to provide temporary support with biohybrid-liver
      assist devices or long-term therapy by replacing the diseased liver with
      functional constructs. A rate-limiting step for TE&RM strategies has been the
      loss of hepatocyte-specific functions after hepatocytes are isolated from their
      highly specialized in vivo microenvironment and placed in in vitro culture
      systems. The identification of a biologic substrate that can maintain a
      functional hepatocyte differentiation profile during in vitro culture would
      advance potential TE&RM therapeutic strategies. The present study compared two
      different biologic substrates for their ability to support human hepatocyte
      function in vitro: porcine-liver-derived extracellular matrix (PLECM) or
      Matrigel. Because Matrigel has been shown to be the most useful matrix for
      static, traditional hepatocyte culture, we directly compared PLECM with Matrigel
      in each experiment. Albumin secretion, hepatic transport activity, and ammonia
      metabolism were used to determine hepatocyte function. Hepatocytes cultured
      between two layers of PLECM or Matrigel showed equally high levels of albumin
      expression and secretion, ammonia metabolism, and hepatic transporter expression
      and function. We conclude that like Matrigel, PLECM represents a favorable
      substrate for in vitro culture of human hepatocytes.

PMID- 19845463
TI  - The development and characterization of an organotypic tissue-engineered human
      esophageal mucosal model.
AB  - There is a demand for a reliable three-dimensional tissue-engineered model of the
      esophageal mucosa for use as an experimental platform for investigating
      esophageal epithelial biology and the pathogenesis of esophageal neoplasia and
      precursor lesions such as Barrett's metaplasia. A number of models have been
      described, but there has been little systematic assessment of the different
      approaches, making selection of a preferred platform difficult. This study
      assesses the properties of organotypic cultures using four different scaffolds
      (human esophageal matrix, porcine esophageal matrix, human dermal matrix, and
      collagen) and two different epithelial cell types (primary human esophageal
      squamous cells and the Het-1A esophageal squamous cell line). Human esophageal
      matrix and dermis did not give consistent results, but porcine esophageal matrix
      and collagen proved more reliable and were studied in greater detail. Both
      matrices supported the formation of a mature stratified epithelium that was
      similar to that of the normal human esophagus, demonstrated by Ki67, CK4, CK14,
      and involucrin staining. However, collagen showed reduced epithelial adherence,
      while fibroblast penetration into the porcine matrix was poor. Composite cultures
      using Het-1A cells formed a hyperproliferative epithelium with no evidence of
      differentiation. We propose human esophageal squamous cells seeded onto porcine
      esophageal matrix as the preferred model of the normal human esophagus.

PMID- 19845464
TI  - Engineering psychology in a changing world.

PMID- 19845466
TI  - Endothelial progenitor populations in differentiating embryonic stem cells. II.
      Drug selection and functional characterization.
AB  - Despite the enormous potential of embryonic stem cells (ESCs) for use in tissue
      engineering and cell therapies, clinical use of ESCs has been deterred by
      difficulties in obtaining desired cell populations without undifferentiated or
      other undesired cell phenotypes. Previously we demonstrated the time-dependent
      variation of endothelial specific promoter activities in differentiating mouse
      ESCs. Here, we evaluated the functional behavior of endothelial cells (ECs)
      selected using a drug resistance gene (Puro(R)) under the control of different EC
      promoters (Flk1, Tie1, and platelet endothelial cell adhesion molecule (PECAM),
      as well as vascular endothelial (VE)-cadherin). All four promoters tested yielded
      cells with EC-specific protein expression and acetylated low density lipoprotein,
      labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate
      (DiI-Ac-LDL) uptake after puromycin treatment. However, the percentage of
      puromycin-surviving cells varied depending on EC promoters, indicating different
      levels of promoter activity. Continuous selection of ECs in puromycin reduced the
      presence of smooth muscle cells or undifferentiated cells. Puro-selected cells
      under all the EC promoters were positive for capillary-like network formation in
      Matrigel. Prostacyclin secretion by ESC-derived ECs showed improvement with
      orbital shear stress exposure corresponding to 0-16 dynes/cm(2); however,
      prostacyclin levels were lower than those seen in immortalized mouse EC lines.
      Tissue plasminogen activator (tPA) secretion by Puro-selected cells was
      comparable to that seen in cell lines, but tPA secretion after shear stress
      exposure showed mixed results, with tPA increasing upon shear under PECAM and
      Tie1 promoters and tPA decreasing upon shear under Flk1 and VE-cadherin
      promoters.

PMID- 19845465
TI  - Passaged adult chondrocytes can form engineered cartilage with functional
      mechanical properties: a canine model.
AB  - It was hypothesized that previously optimized serum-free culture conditions for
      juvenile bovine chondrocytes could be adapted to generate engineered cartilage
      with physiologic mechanical properties in a preclinical, adult canine model.
      Primary or passaged (using growth factors) adult chondrocytes from three adult
      dogs were encapsulated in agarose, and cultured in serum-free media with
      transforming growth factor-beta3. After 28 days in culture, engineered cartilage
      formed by primary chondrocytes exhibited only small increases in
      glycosaminoglycan content. However, all passaged chondrocytes on day 28
      elaborated a cartilage matrix with compressive properties and glycosaminoglycan
      content in the range of native adult canine cartilage values. A preliminary
      biocompatibility study utilizing chondral and osteochondral constructs showed no
      gross or histological signs of rejection, with all implanted constructs showing
      excellent integration with surrounding cartilage and subchondral bone. This study
      demonstrates that adult canine chondrocytes can form a mechanically functional,
      biocompatible engineered cartilage tissue under optimized culture conditions. The
      encouraging findings of this work highlight the potential for tissue engineering
      strategies using adult chondrocytes in the clinical treatment of cartilage
      defects.

PMID- 19845467
TI  - Differential alteration of heat shock protein 90 in mice modifies glucocorticoid
      receptor function and susceptibility to trauma.
AB  - Heat shock protein 90 (Hsp90), encoded by the murine hsp84 and hsp86 genes in
      mice, is a pivotal regulator of glucocorticoid receptor (GR) function in the
      hypothalamus-pituitary-adrenal axis and affords stress protection. To explore the
      underlying molecular mechanisms of strain susceptibility to traumatic stress, we
      investigated the alteration by Hsp90 of the function of the glucocorticoid
      glucocorticoid receptor (GC-GR) pathway in attenuating stress responses in
      C57BL/6 and BALB/c mice using the whole-body blast injury (WBBI) model. We found
      that C57BL/6 mice had a lower WBBI-induced mortality, higher nuclear GR level,
      and higher glucocorticoid-response element (GRE) binding activity than BALB/c
      mice. This study is the first report identifying four genetic variations of the
      murine hsp84 gene: 226A>C, 996G>C, 1483G>C, and 2000G>T. These nucleotide changes
      occur in the functional domains associated with the nuclear/cytosolic
      translocation of GR, GR-Hsp90 interaction, ATP binding, and self-dimerization of
      Hsp90, respectively. Further, we used a specific Hsp90 inhibitor, geldanamycin
      (GA), to assess the role of Hsp90 in the discriminative traumatic response in
      C57BL/6 mice. Pretreatment with GA reduced nuclear GR levels and GRE binding
      activity, and enhanced WBBI-induced mortality. These findings suggest that Hsp90
      may underlie the strain-selective (C57BL/6 versus BALB/c) susceptibility to WBBI
      by mediating the nuclear translocation of GRs and GRE binding. Thus,
      pharmacological manipulation of Hsp90 may represent a therapeutic strategy to
      modify the function of the GC-GR pathway and traumatic stress response.

PMID- 19845468
TI  - PTEN and TRP53 independently suppress Nanog expression in spermatogonial stem
      cells.
AB  - Mammalian spermatogonial stem cells are a special type of adult stem cells
      because they can contribute to the next generation. Knockout studies have
      indicated a role for TRP53 and PTEN in insulating male germ cells from
      pluripotency, but the mechanism by which this is achieved is largely unknown. To
      get more insight in these processes, an RNAi experiment was performed on the
      mouse spermatogonial stem cell line GSDG1. Lipofectaminemediated transfection of
      siRNAs directed against Trp53 and Pten resulted in decreased expression levels as
      determined by quantitative RT-PCR and immunoblotting. The effects of knockdown
      were examined by determining the expression levels of genes that are involved in
      reprogramming and pluripotency of cells, specifically Nanog, Eras, c-Myc, Klf4,
      Oct4, and Sox2. Additionally, the effects of TRP53 or PTEN knockdown on Plzf and
      Ddx4 expression were measured, which are highly expressed in spermatogonial stem
      cells and differentiating male germ cells, respectively. The main finding of this
      study is that knockdown of Trp53 and Pten independently resulted in significantly
      higher expression levels of the pluripotency-associated gene Nanog, and we
      hypothesize that TRP53 and PTEN mediated repression is important for the
      insulation of male germ cells from pluripotency.

PMID- 19845469
TI  - Hydrogen sulfide: the third gasotransmitter in biology and medicine.
AB  - The last two decades have seen one of the greatest excitements and discoveries in
      science, gasotransmitters in biology and medicine. Leading the trend by nitric
      oxide and extending the trudge by carbon monoxide, here comes hydrogen sulfide
      (H(2)S) who builds up the momentum as the third gasotransmitter. Being produced
      by different cells and tissues in our body, H(2)S, alone or together with the
      other two gasotransmitters, regulates an array of physiological processes and
      plays important roles in the pathogenesis of various diseases from
      neurodegenerative diseases to diabetes or heart failure, to name a few. As a
      journal dedicated to serve the emergent and challenging field of H(2)S biology
      and medicine, Antioxidant and Redox Signaling assembles the most recent
      discoveries and most provoking ideas from leading scientists in H(2)S fields,
      which were communicated in the First International Conference of H(2)S in Biology
      and Medicine, and brings them to our readers in two Forum Issues. Through
      intellectual exchange and intelligent challenge with an open-mind approach, we
      can reasonably expect that sooner rather than later the exploration of metabolism
      and function of H(2)S will provide solutions for many of the biological mysteries
      of life and pave way for the arrival of many more gasotransmitters.

PMID- 19845470
TI  - Paying the price for late starts and early stops: racial and sex disparities in
      HIV-related mortality.

PMID- 19845471
TI  - Google trends: a web-based tool for real-time surveillance of disease outbreaks.
AB  - Google Flu Trends can detect regional outbreaks of influenza 7-10 days before
      conventional Centers for Disease Control and Prevention surveillance systems. We
      describe the Google Trends tool, explain how the data are processed, present
      examples, and discuss its strengths and limitations. Google Trends shows great
      promise as a timely, robust, and sensitive surveillance system. It is best used
      for surveillance of epidemics and diseases with high prevalences and is currently
      better suited to track disease activity in developed countries, because to be
      most effective, it requires large populations of Web search users. Spikes in
      search volume are currently hard to interpret but have the benefit of increasing
      vigilance. Google should work with public health care practitioners to develop
      specialized tools, using Google Flu Trends as a blueprint, to track infectious
      diseases. Suitable Web search query proxies for diseases need to be established
      for specialized tools or syndromic surveillance. This unique and innovative
      technology takes us one step closer to true real-time outbreak surveillance.

PMID- 19845472
TI  - Racial and sex disparities in life expectancy losses among HIV-infected persons
      in the united states: impact of risk behavior, late initiation, and early
      discontinuation of antiretroviral therapy.
AB  - BACKGROUND: Most persons with human immunodeficiency virus (HIV) infection in the
      United States present to care with advanced disease, and many patients
      discontinue therapy prematurely. We sought to evaluate sex and racial/ethnic
      disparities in life-years lost as a result of risk behavior, late presentation,
      and early discontinuation of HIV care, and we compared these survival losses for
      HIV-infected persons with losses attributable to high-risk behavior and HIV
      disease itself. METHODS: With use of a state-transition model of HIV disease, we
      simulated cohorts of HIV-infected persons and compared them with uninfected
      individuals who had similar demographic characteristics. We estimated non-HIV
      related mortality with use of risk-adjusted standardized mortality ratios, as
      well as years of life lost because of late presentation and early discontinuation
      of antiretroviral therapy (ART) for HIV infection. Data from the national HIV
      Research Network, stratified by sex and race/ethnicity, were used for estimating
      CD4+ cell counts at ART initiation. RESULTS: For HIV-uninfected persons in the
      United States who have risk profiles similar to those of individuals with HIV
      infection, the projected life expectancy, starting at 33 years of age, was 34.58
      years, compared with 42.91 years for the general US population. Those with HIV
      infection lost an additional 11.92 years of life if they received HIV care
      concordant with guidelines; late treatment initiation resulted in 2.60 additional
      years of life lost, whereas premature ART discontinuation led to 0.70 more years
      of life lost. Losses from late initiation and early discontinuation were greatest
      for Hispanic individuals (3.90 years). CONCLUSIONS: The high-risk profile of HIV
      infected persons, HIV infection itself, as well as late initiation and early
      discontinuation of care, all lead to substantial decreases in life expectancy.
      Survival disparities resulting from late initiation and early discontinuation of
      therapy are most pronounced for Hispanic HIV-infected men and women.
      Interventions focused on risk behaviors, as well as on earlier linkage to and
      better retention in care, will lead to improved survival for HIV-infected persons
      in the United States.

PMID- 19845474
TI  - Adenovirus DNA positivity in nasopharyngeal aspirate preceding hematopoietic stem
      cell transplantation: a very strong risk factor for adenovirus DNAemia in
      pediatric patients.
AB  - Human adenovirus (HAdV)-positive nasopharyngeal aspirate preceding hematopoietic
      stem cell transplantation was prospectively analyzed in 62 patients. By
      multivariate Cox proportional hazard models, HAdV-positive nasopharyngeal
      aspirate was the only predictor for HAdV DNAemia after hematopoietic stem cell
      transplantation (P < .001). HAdV DNAemia was a predictor for alloreactive
      disease. Early detection and intervention might help to prevent HAdV disease
      after hematopoietic stem cell transplantation.

PMID- 19845473
TI  - Trends in multidrug treatment failure and subsequent mortality among
      antiretroviral therapy-experienced patients with HIV infection in North America.
AB  - BACKGROUND: Although combination antiretroviral therapy continues to evolve, with
      potentially more effective options emerging each year, the ability of therapy to
      prevent multiple regimen failure and mortality in clinical practice remains
      poorly defined. METHODS: Sixteen cohorts representing over 60 sites contributed
      data on all individuals who initiated combination antiretroviral therapy. We
      identified those individuals who experienced virologic failure (defined as a
      human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified
      therapy, and subsequently had a second episode of virologic failure. Multivariate
      Cox regression was used to assess factors associated with time to second regimen
      failure and the time to death after the onset of second regimen failure. RESULTS:
      Of the 42,790 individuals who received therapy, 7159 experienced a second
      virologic failure. The risk of second virologic failure decreased from 1996 (56
      cases per 100 person-years) through 2005 (16 cases per 100 person-years; P <
      .001). The cumulative mortality after onset of second virologic failure was 26%
      at 5 years and decreased over time. A history of AIDS, a lower CD4(+) T cell
      count, and a higher plasma HIV RNA level were each independently associated with
      mortality. Similar trends were observed when analysis was limited to the subset
      of previously treatment-naive patients CONCLUSIONS: Although the rates of
      multiple regimen failure have decreased dramatically over the past decade,
      mortality rates for those who have experienced failure of at least 2 regimens
      have remained high. Plasma HIV RNA levels, CD4(+) T cell counts at time of
      treatment failure, and a history of AIDS remain independent risk factors for
      death, which emphasizes that these factors remain important targets for those in
      need of more-aggressive therapeutic interventions.

PMID- 19845475
TI  - When guidelines don't guide the physician.

PMID- 19845476
TI  - Dilemmas in the management of syphilis: a survey of infectious diseases experts.
AB  - We surveyed infectious diseases consultants to determine how they manage syphilis
      when there are insufficient data to guide management or when guidelines cannot be
      followed because of a lack of available definitive diagnostic tests. Most
      providers did not have access to dark-field microscopy. We found variation in
      management of syphilis, especially for patients with human immunodeficiency virus
      infection.

PMID- 19845477
TI  - Treatment with a toll-like receptor inhibitory GpG oligonucleotide delays and
      attenuates lupus nephritis in NZB/W mice.
AB  - Activation of the innate immune system by DNA containing hypomethylated CpG
      motifs has been implicated in the pathogenesis of systemic lupus erythematosus
      (SLE). Here, we examined the consequences of immunostimulatory CpG
      oligodeoxynucleotide (ODN) and inhibitory GpG-ODN treatment in the NZB x NZW F1
      (NZB/W) murine model of SLE. Beginning at 5 months of age, we administered CpG
      ODN or GpG-ODN at regular intervals to female NZB/W animals. We also determined
      the effects of ODN administration on NZB/W mouse lymphocyte function, and the
      specificity of ODN binding to Toll-like receptors (TLRs) other than TLR-9. While
      CpG-ODN treatment did not appear to have a major impact on disease severity, GpG
      ODN treatment significantly delayed the onset of proteinuria in NZB/W mice.
      Interestingly, short-term GpG-ODN treatment promoted Th2-type T and B cell
      responses, and inhibited B lymphocyte proliferation in vitro. On the other hand,
      extended GpG-ODN treatment did not result in sustained Th2 responses or
      significantly reduced renal disease. Moreover, the binding of CpG-ODN and GpG-ODN
      was not restricted to TLR-9 as both ODNs also interacted with TLR-3, TLR-7, and
      TLR-8. Taken together, the data indicate that the protective mechanism of GpG-ODN
      treatment in the NZB/W model of lupus nephritis involves modulating T cell
      cytokine profiles and B lymphocyte activation through the inhibition of several
      TLRs, including TLR-7 and TLR-9.

PMID- 19845478
TI  - Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem
      cells as modulators of diabetogenesis.
AB  - The increase of pro-inflammatory cytokines and oxidative stress leads to beta
      cell damage and promotes beta-cells apoptosis, in types I and II of diabetes
      mellitus. Therefore, blocking of pro-inflammatory cytokines should be an
      effective way for the treatment of diabetes mellitus. When IL-1 occupies its
      receptor, various pro-inflammatory events are initiated including the synthesis
      and releases of chemokines and these chemokines attract neutrophils, macrophages,
      and lymphocytes that cause tissue inflammation. IL-1Ra is a naturally occurring
      cytokine and is the inhibitor of IL-1. When IL-1Ra binds to the IL-1 receptor,
      binding of IL-1 is blocked by IL-1Ra and pro-inflammatory signal from IL-1
      receptor is stopped. There are mounting evidences to suggest that anti
      inflammatory IL-1Ra reduces the inflammatory effects of IL-1 and preserves cell
      function in both types of diabetes. Therefore, IL-1Ra maybe a new therapeutic
      agent for diabetes mellitus types I and II. Mesenchymal stem cells (MSCs) are
      self-renewable multipotent stromal cells that have immunomodulatory capacity.
      Recently, well characterized subpopulations of MSCs which express IL-1Ra have
      been described. IL-1Ra expressed by these MSCs effectively binds to IL-1 receptor
      and protects tissues from inflammation-induced injuries. It has been previously
      shown that bone marrow-derived MSC therapy could be considered for the treatment
      of diabetes mellitus type 1 and complications of diabetes mellitus. This review
      presents understanding of potential use of IL-1Ra and MSCs as modulators of
      diabetogenesis.

PMID- 19845480
TI  - Tissue-specific cross-reactivity of connexin32 antibodies: problems and solutions
      unique to the central nervous system.
AB  - Gap junction proteins are a highly homologous family of 21 connexins. Here, the
      authors describe a tissue-specific technical artifact complicating analysis of
      connexin32 protein expression in the central nervous system. The authors show
      that in brain, but not liver, eight commonly employed antibodies exhibit a higher
      affinity for a cross-reactive protein that masks the detection of connexin32.
      Cross-reactivity is evident in Western blot analyses when proteins are subjected
      to reducing/denaturing conditions but not immunoprecipitation or
      immunofluorescent applications. Through bioinformatic analyses, tested by sucrose
      gradient fractionation and immunoblotting of lysates from connexin null-mutant
      mice, the authors show that the cross-reactive protein is not found in the same
      cellular compartments as connexin32 and is likely not a member of the connexin
      family. These findings are presented with the intent of helping to reduce the
      amount of time laboratories currently expend in validating changes in connexin32
      expression in the central nervous system.

PMID- 19845481
TI  - Development of silk fibroin-based beads for immobilized cell fermentations.
AB  - Silk fibroin was evaluated as a new matrix for immobilized cell fermentation.
      Silk fibroin was extracted from Bombyx mori cocoon, purified, concentrated in
      polyethylene glycol solution and diluted to 3 wt% with distilled water. This
      fibroin solution was used to encapsulate sensitive cells of the probiotic strain,
      Bifidobacterium longum ATCC 15707. Polymer droplets produced with an encapsulator
      were collected in liquid nitrogen and lyophilized. A low overall survival of 0.2%
      was measured after lyophilization. Lyophilized beads were hardened for 24 h under
      vacuum with an atmosphere of 89% relative humidity. The inoculated beads were
      colonized in two successive batch fermentations. Structure of silk fibroin beads
      and colonization of cells were examined with scanning electron microscopy.
      Colonized beads were tested in continuous fermentations for cell production. A
      biomass productivity of 1.7 x 10(9) CFU ml(-1) h(-1) was achieved, which was
      limited by loss of bead structure. This instability might be due to bead
      degradation by proteolytic activity of cells and/or limited mechanical stability
      during continuous fermentation in the stirred tank reactor.

PMID- 19845484
TI  - Niosomes in sustained and targeted drug delivery: some recent advances.
AB  - Niosomes represent an emerging class of novel vesicular systems. They are
      composed of nonionic surfactants which are biodegradable and relatively nontoxic.
      They were developed as stable and inexpensive alternatives to liposomes. Since
      their early introduction to cosmetic industry their role has diversified to other
      application areas. They are now being ardently explored as potential carriers for
      sustained and targeted drug delivery. In addition to conventional, oral, and
      parenteral routes, they are amenable to be delivered by ocular, transdermal,
      vaginal, and inhalation routes. Delivery of biotechnological products including
      vaccine delivery with niosomes is also an interesting and promising research
      area. The introduction of provesicular approach in the form of proniosomes has
      further increased the relevance of these systems. More concerted research
      efforts, however, are still required to realize the full potential of these novel
      systems. This review considers the current status and explores the potential of
      niosomes in drug delivery with special attention to their role in drug targeting.
      Their methods of preparation, formulation aspects, advantages, limitations, and
      applications are also discussed.

PMID- 19845485
TI  - Diagnostic and therapeutic applications of iontophoresis.
AB  - Owing to the excellent barrier properties of the stratum corneum, transdermal
      delivery remains a challenge for a high number of molecules. Iontophoresis is a
      noninvasive technique which uses a low current to administer polar and charged
      species through the skin, thereby enlarging the range of drug candidates for
      transdermal administration. Unlike other techniques of transdermal delivery
      enhancement, iontophoresis acts on the molecule itself allowing a better control
      of the dose applied. The symmetry of the technique can be employed for controlled
      extraction, allowing a relation to be established between extracted flux and
      subdermal concentration. This opened the way for innovative applications, notably
      in the field of noninvasive monitoring of glucose and xenobiotics. Rather than
      being an extensive review of the literature, this article summarizes the basic
      rules governing iontophoretic transport, discusses advantages and limitations of
      the technique, and provides an overview of promising therapeutic applications.

PMID- 19845486
TI  - The effect of intracellular delivery of catalase and antisense oligonucleotides
      to NF-kappaB using albumin microcapsules in the endotoxic shock model.
AB  - Microencapsulated (MC) catalase has been shown to inhibit H(2)O(2) and tumor
      necrosis factor (TNF) in vitro after endotoxin stimulation. It is the purpose of
      this study to determine whether MC catalase improves pro-inflammatory cytokine
      inhibition and mortality in an endotoxic shock model in vivo. We also examined
      whether MC catalase and antisense oligonucleotides (ASO) to nuclear factor kappaB
      (NF-kappaB) together improved survival by inhibiting pro-inflammatory cytokines
      using different mechanisms. METHODS: Albumin microcapsules containing catalase
      and ASO to NF-kappaB were prepared 2-7 microm in size by using a Buchi spray
      dryer. Progressively increasing doses of MC catalase, MC ASO to NF-kappaB, and
      the combination were given to rats before the administration of Escherichia coli
      endotoxin. Results demonstrated 60% survival in rats given 15 mg/kg MC catalase,
      70% survival with 20 mg/kg MC ASO NF-kappaB, and 80% survival with the
      combination. TNF was inhibited by 53% in the MC catalase group 4 h after
      endotoxin administration, 43% in the ASO NF-kappaB group, and 78% in the
      combination group compared to controls. In conclusion, this study demonstrates
      the effectiveness of MC intracellular delivery of the naturally occurring
      antioxidant catalase in improving animal survival. The addition of ASO to NF
      kappaB improved both cytokine inhibition and animal survival in endotoxic shock.

PMID- 19845487
TI  - The effect of intracellular antioxidant delivery (catalase) on hydrogen peroxide
      and proinflammatory cytokine synthesis: a new therapeutic horizon.
AB  - Reactive oxygen species synthesized by endothelial cells may be responsible for
      cell damage and altered physiologic function. After endotoxin stimulation, free
      radicals including H(2)O(2) are produced. We have developed a method of
      intracellular drug delivery using albumin microcapsules. Catalase would be an
      excellent compound to alter H(2)O(2) production. However, the large molecular
      size of catalase limits cellular penetration. Endothelial cells have been
      previously shown to readily phagocytoze albumin microcapsules. METHODS: Catalase
      was added to an albumin solution to form a 10% solution of catalase. Microspheres
      from 2 to 7 microm in size were formed using a Bucchi spray dryer. Human
      endothelial cells were incubated with varying concentrations of microencapsulated
      catalase. The cells were then exposed to Escherichia coli endotoxin to determine
      if increased intracellular penetration of catalase would inhibit H(2)O(2),
      nitrate, and cytokine synthesis. RESULTS: There was a 7.2-fold increase in
      endothelial intracellular catalase after 48 h incubation. H(2)O(2) was inhibited
      by 72%, nitrate 96%, TNF 90%, IL1 21%, IL6 42%. CONCLUSIONS: These results
      demonstrate that inhibition of H(2)O(2) as a result of increased intracellular
      delivery of catalase inhibits proinflammatory cytokine synthesis after endotoxin
      exposure.

PMID- 19845488
TI  - Mild hyperthermia as a potential mechanism to locally enhance cell growth
      kinetics.
AB  - The effect of mild hyperthermia on growth kinetics of two human glioma and one
      mouse fibroblast cell line was evaluated over a 12 h (short-term) or 7 day (long
      term) period. All cell lines showed growth enhancement at 38 degrees C, although
      the effect in C3H 10T (1/2) mouse fibroblasts was more pronounced and had a more
      rapid onset than in U87MG or LN71 glioma cells. At 39 degrees C, growth of C3H
      10T (1/2) cells was slightly reduced and glioma cell lines similar to that of
      their respective 37 degrees C controls. At 40 degrees C, C3H 10T (1/2) cells
      showed a more rapid and dramatic growth reduction than glioma cell lines and
      accumulated in both G(0)/G(1) and G(2) checkpoint compartments. In contrast,
      U87MG cells accumulated only in G(2) and LN71 showed no checkpoint accumulation.
      The findings indicate that cell lines are differentially responsive to small
      temperature elevations. If similar differences exist between normal and diseased
      human tissues, local application of mild hyperthermia might offer a noninvasive
      and cost-effective method to achieve local enhancement of drugs that target
      proliferating tissue.

PMID- 19845489
TI  - Novel preparation of transdermal drug-delivery patches and functional wound
      healing materials.
AB  - The application of an electric field to a flowing medium can result in the
      formation of microscale and nanoscale structures suitable for drug delivery
      applications. We show that the design of the drug carrier can be varied and the
      release mechanism can be controlled by changing the physical state of the
      component containing the active agent. The structures formed include loaded
      micrometer-scale tubes and microcapsules and nanocapsules, which can also be
      utilized together to fabricate patches and wound healing materials. The aim of
      this study was to demonstrate novel processing of such patches and wound
      dressings. The processing used to generate these structures is carried out at the
      ambient temperature and is a versatile one-step operation suitable for a range of
      materials with low running costs and set-up costs without the degradation of the
      active drug component. The process can be multiplexed and requires no solvent
      extraction. It also offers pharmaceutical applications outside the remit of the
      potential uses presented.

PMID- 19845490
TI  - Treatment outcomes of sinonasal inverted papillomas according to surgical
      approaches.
AB  - CONCLUSIONS: The midfacial degloving approach is a favorable option for advanced
      sinonasal inverted papilloma with a fair recurrence rate, and can replace the
      lateral rhinotomy approach, which is considered too invasive for benign tumor due
      to its facial scar. OBJECTIVE: This study aimed to assess the treatment outcomes
      of advanced sinonasal inverted papillomas according to surgical approaches over a
      20-year period. MATERIAL AND METHODS: We retrospectively reviewed clinic,
      operative, radiologic, and pathologic records of patients with surgically treated
      sinonasal inverted papilloma, and compared recurrence rates of patients treated
      with the endoscopic approach, midfacial degloving approach, and lateral rhinotomy
      approach in each Krouse stage of inverted papilloma. RESULTS: A total of 114
      patients were diagnosed and treated surgically for the sinonasal inverted
      papilloma. The follow-up period ranged from 10 months to 12 years (mean 2.8
      years). The overall recurrence rate was 23.7% (27/114). Among the patients
      classified as Krouse stage III, 33.3% (9/27) of the endoscopic approach group,
      11.1% (2/18) of the midfacial degloving approach group, and 25.0% (2/8) of the
      lateral rhinotomy approach group had recurrences.

PMID- 19845491
TI  - Plasticity of tonotopic maps in humans: influence of hearing loss, hearing aids
      and cochlear implants.
AB  - CONCLUSION: This paper reviews psychoacoustical and electrophysiological evidence
      for reorganization of the human central auditory system in case of auditory
      deprivation and rehabilitation. OBJECTIVE: To investigate the plasticity of
      cortical tonotopic maps in cochlear-damaged subjects. METHODS: Frequency
      discrimination scores were analysed in subjects with high frequency hearing loss
      to test for potential perceptual correlates of auditory deprivation- and
      rehabilitation-induced plasticity. In cochlear implant patients, electrically
      evoked auditory cortical responses were obtained using EEG to study scalp
      potential maps. RESULTS: Perceptual changes in frequency discrimination were
      observed at the lesion-edge frequency of steeply sloping hearing loss. Although
      these results are not direct proof of cortical plasticity, no peripheral
      phenomenon has been found to explain them. The reversal of such auditory
      deprivation-induced plasticity, a phenomenon that may be termed rehabilitation
      plasticity, can be studied in hearing-impaired subjects fitted with a hearing
      aid. Cochlear implant subjects provide another interesting model for studying
      rehabilitation plasticity in that even profound to total deafness is made
      partially reversible by cochlear implantation. We found that the auditory cortex
      of deaf subjects with at least 3 months of cochlear implant experience is
      organized in a way similar to the tonotopy described in normal-hearing subjects.

PMID- 19845492
TI  - Screening for antenatal depression with the Edinburgh Depression Scale.
AB  - This study aimed to evaluate how precise the Edinburgh Depression Scale (EDS) is
      in screening for major depressive disorder (MDD) during different periods of
      pregnancy. A random sample of 230 pregnant women was interviewed in the first,
      second, and third trimesters of pregnancy using the EDS and not-patient version
      of the Structured Clinical Interview for DSM-III-R (SCID-NP). We evaluated test
      retest reliability of the EDS; area under the ROC curve (AUC), sensitivity,
      specificity, and positive predictive value (PPV) of the EDS against the SCID-NP
      diagnoses in the first, second, and third trimesters of pregnancy. Test-retest
      reliability of the EDS was 0.81 (p < 0.001). An optimal cutoff score of the EDS
      for screening current SCID-NP diagnosis of MDD was 12 and higher in the first
      trimester of pregnancy (AUC 0.94, sensitivity 92%, specificity 95%, and PPV 52%)
      and 11 and higher in the second and third trimesters of pregnancy (AUC 0.96 and
      0.90, respectively; sensitivity 100% and 88%, respectively; specificity 92% and
      92%, respectively; PPV 25% and 29%, respectively). The EPDS is a reliable
      instrument for repeated evaluations of depressive symptoms during pregnancy. It
      has a good sensitivity and specificity for detecting antenatal MDD with optimal
      cutoff of 11/12 or higher.

PMID- 19845493
TI  - Quality of life outcomes in pregnancy and postpartum complicated by hypertensive
      disorders, gestational diabetes, and preterm birth.
AB  - Health problems can develop during a pregnancy, turning it into a high risk. The
      aim of this study was to explore the influence of hypertensive disorders,
      gestational diabetes, and preterm birth as risk factors for health-related
      quality of life (HRQL) and depressive symptoms during late pregnancy and
      postpartum. A prospective, longitudinal study was performed with three
      assessments. Ninety women were recruited in the study including 29 controls. HRQL
      was measured using the WHO-QOL-BREF questionnaire. Depressive symptoms were
      assessed with the Edinburgh Postnatal Depression Scale (EPDS). Statistical
      analyses were performed using ANOVA and the chi-square test to explore HRQL and
      depressive symptoms between three pregnancy risk groups and controls. Women of
      the preterm group had statistically significant higher depression scores and
      lower HRQL scores on the physical domain during pregnancy than those without
      complications. Women with hypertensive disorders showed the second most
      depressive symptoms. Physical and global HRQL improved and depressive symptoms
      decreased significantly from late pregnancy and early postpartum period to late
      postpartum. Pregnant specific health problems, especially the risk for preterm
      delivery is associated with more depressive symptoms and decreased HRQL in
      pregnancy. Guidance and communication for these women is important. The
      counseling should be multi professional to reduce childbirth burdens.

PMID- 19845494
TI  - P2X7-mediated chemoprevention of epithelial cancers.
AB  - BACKGROUND: Anti-apoptotic mechanisms contribute to the development of cancer.
      The purinergic ligand-gated ion channel receptor P2X(7) system is an important
      pro-apoptosis modulator in epithelial cells, and augmentation of P2X(7)-mediated
      apoptosis has been proposed as a novel pharmacological modality for
      chemoprevention and treatment of epithelial cancers. OBJECTIVE: This review
      focuses on the progress towards clinical application of therapies that directly
      modulate P2X(7)-mediated apoptosis. This paper reviews and discusses P2X(7)
      mediated apoptosis in the context of prevention and growth-control of epithelial
      cancer cells, and summarizes recent data in the mouse skin model in vivo.
      METHODS: Data for this review were identified from the PubMed and MEDLINE
      databases. SUMMARY/CONCLUSIONS: The growing understanding of mechanisms of P2X(7)
      mediated apoptosis has generated a novel strategy for targeting directly and
      specifically skin neoplasia. The data link directly, for the first time,
      upregulation of apoptosis with cancer chemoprevention. Striking antitumor
      efficacy has been achieved in the rodent cancer model, and it is likely that the
      recently gained wealth of knowledge about the mechanisms of P2X(7)-control of
      apoptosis will eventually be translated into new clinical therapies for
      epithelial cancers.

PMID- 19845495
TI  - Assessment of survival in a 2-year comparative study of lanthanum carbonate
      versus standard therapy.
AB  - OBJECTIVE: Epidemiological data link elevated levels of serum phosphorus with
      increased mortality among patients with chronic kidney disease. Recent data also
      suggest improved survival with the use of dietary phosphate binders in patients
      on dialysis. However, few studies have comprehensively evaluated the survival
      benefit associated with different phosphate binders. A post-hoc survival analysis
      was undertaken of lanthanum carbonate (Fosrenol *) versus standard therapy.
      RESEARCH DESIGN AND METHODS: Patients on dialysis enrolled in a phase 3, 2-year,
      comparative safety study were randomized 1:1 to lanthanum carbonate or standard
      therapy to treat serum phosphorus to a target of < or =5.9 mg/dL (1.90 mmol/L).
      Patients (N = 1354) were followed up for survival status during, or after
      completion of or discontinuation from the study. MAIN OUTCOME MEASURES: Survival
      was measured by time from first dose of study medication to all-cause mortality
      or last contact. RESULTS: The distribution of follow-up time was similar in the
      lanthanum carbonate and standard therapy groups (mean 23.7 versus 23.9 months
      [median 27.0 versus 26.0 months], respectively). Serum phosphorus levels were
      similar across treatment groups, as patients were treated to target. At follow
      up, 19.9% (135/680) of patients treated with lanthanum carbonate had died versus
      23.3% (157/674) on standard therapy (log-rank p = 0.18). In the subgroup of
      patients aged >65 years (n = 336), 27.0% (44/163) of lanthanum-carbonate-treated
      patients had died compared with 39.3% (68/173) on standard therapy (log-rank p =
      0.04). CONCLUSION: In these survival analyses, overall mortality was similar in
      the lanthanum carbonate and standard therapy groups, but results suggest that
      there was a survival benefit associated with lanthanum carbonate treatment for
      patients aged >65 years, who are likely to carry the greatest burden of vascular
      calcification. These results were similar to those observed in the Dialysis
      Clinical Outcomes Revisited study, a prospective trial of sevelamer hydrochloride
      designed to assess survival.

PMID- 19845502
TI  - Anticancer activities and mechanisms of bisdioxopiperazine compounds probimane
      and MST-16.
AB  - Bisdioxopiperazine compounds, including ICRF-154 and razoxane (ICRF-159, Raz),
      are anticancer agents developed in the UK specifically targeting tumor
      metastases. Further two bisdioxopiperazine derivatives, probimane (Pro) and MST
      16, have been synthesized at the Shanghai Institute of Materia Medica, Chinese
      Academy of Sciences, PR China after 1980. Anticancer activities and mechanisms of
      Pro and MST-16 compared with Raz, especially for antiproliferative and
      antimetastatic effects in vivo and in vitro, have been systematically evaluated
      in this lab as well as by other authors in China. Novel molecular mechanisms
      especially relating to the inhibition of tumor metastasis between probimane and
      razoxane have been especially explored and explained, including pathways of
      inhibitions against calmodulin, sialic acid, lipoperoxidation, fibrinogen, cell
      movement and the cell-cycle arrest. The distributions and excretions of (14)[C]
      Pro in mice have been carefully monitored long before for explaining the
      relationship of pharmacological data between in vitro and in vivo evaluations.
      Pro is more soluble in water and more strongly active against tumors than Raz. In
      our point of view, Pro seems to inherit and retain most of the targets and
      pathways of other bisdioxopiperazine compounds currently in use and is
      cytotoxically more potent than the rest of bisdioxopiperazine compounds.
      Therefore, there is a great potential and significance for further
      investigations.

PMID- 19845503
TI  - Antitumor activities of interleukin-27 on melanoma.
AB  - The worldwide incidence of malignant melanoma has been steadily increasing, and
      it has become a major public health problem in many countries. Melanoma has been
      considered as a prototypical "immunogenic" tumor on the basis of clinical
      observations showing that primary lesions can spontaneously regress and that
      immunosuppressed individuals have an increased incidence of melanoma. Thus,
      various immunological therapies have been intensively conducted for the treatment
      of melanoma. Interleukin(IL)-27 is a IL-12-related heterodimeric cytokine
      composed of p28 and EBV-induced gene 3 subunits that are structurally related to
      the p35 and p40 subunits of IL-12, respectively. Recent studies reveal that IL-27
      exhibits not only potent antitumor immune activities via cytotoxic T lymphocytes
      or natural killer cells but also an antiangiogenic effect. We recently clarified
      that IL-27 possesses an antiproliferative activity on melanoma cells. This review
      summarizes anti-tumor responses induced by IL-27 and novel anti-melanoma
      activities of IL-27.

PMID- 19845504
TI  - Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes
      to tumour growth, invasion and metastasis.
AB  - mPGES-1 (microsomal prostaglandin E synthase-1) is a stimulus-inducible enzyme
      that functions downstream of COX (cyclo-oxygenase)-2 in the PGE2 (prostaglandin
      E2)-biosynthesis pathway. Although COX-2-derived PGE2 is known to play a role in
      the development of various tumours, the involvement of mPGES-1 in carcinogenesis
      has not yet been fully understood. In the present study, we used LLC (Lewis lung
      carcinoma) cells with mPGES-1 knockdown or overexpression, as well as mPGES-1
      deficient mice to examine the roles of cancer cell- and host-associated mPGES-1
      in the processes of tumorigenesis in vitro and in vivo. We found that siRNA
      (small interfering RNA) silencing of mPGES-1 in LLC cells decreased PGE2
      synthesis markedly, accompanied by reduced cell proliferation, attenuated
      Matrigel invasiveness and increased extracellular matrix adhesion. Conversely,
      mPGES-1-overexpressing LLC cells showed increased proliferating and invasive
      capacities. When implanted subcutaneously into wild-type mice, mPGES-1-silenced
      cells formed smaller xenograft tumours than did control cells. Furthermore, LLC
      tumours grafted subcutaneously into mPGES-1-knockout mice grew more slowly than
      did those grafted into littermate wild-type mice, with concomitant decreases in
      the density of microvascular networks, the expression of pro-angiogenic vascular
      endothelial growth factor, and the activity of matrix metalloproteinase-2. Lung
      metastasis of intravenously injected LLC cells was also significantly less
      obvious in mPGES-1-null mice than in wild-type mice. Thus our present approaches
      provide unequivocal evidence for critical roles of the mPGES-1-dependent PGE2
      biosynthetic pathway in both cancer cells and host microenvironments in tumour
      growth and metastasis.

PMID- 19845505
TI  - Targeting of inositol 1,4,5-trisphosphate receptor to the endoplasmic reticulum
      by its first transmembrane domain.
AB  - Targeting of IP3R (inositol 1,4,5-trisphosphate receptors) to membranes of the ER
      (endoplasmic reticulum) and their retention within ER or trafficking to other
      membranes underlies their ability to generate spatially organized Ca2+ signals. N
      terminal fragments of IP3R1 (type 1 IP3R) were tagged with enhanced green
      fluorescent protein, expressed in COS-7 cells and their distribution was
      determined by confocal microscopy and subcellular fractionation. Localization of
      IP3R1 in the ER requires translation of between 26 and 34 residues beyond the end
      of the first transmembrane domain (TMD1), a region that includes TMD2 (second
      transmembrane domain). Replacement of these post-TMD1 residues with unrelated
      sequences of similar length (24-36 residues) partially mimicked the native
      residues. We conclude that for IP3R approx. 30 residues after TMD1 must be
      translated to allow a signal sequence within TMD1 to be extruded from the
      ribosome and mediate co-translational targeting to the ER. Hydrophobic residues
      within TMD1 and TMD2 then ensure stable association with the ER membrane.

PMID- 19845506
TI  - Reversible bleb formation in mast cells stimulated with antigen is
      Ca2+/calmodulin-dependent and bleb size is regulated by ARF6.
AB  - Mast cells stimulated with antigen undergo extensive changes in their
      cytoskeleton. In the present study, we assess the impact of actin-modifying drugs
      and report that, in the presence of cytochalasin D, mast cells stop membrane
      ruffling, but instead bleb. Bleb formation is reversible following washout of
      cytochalasin D and occurs in an actin-polymerization-dependent manner. Bleb
      formation is inhibited by expression of constitutively active ezrin-T567D.
      Blebbing is also inhibited by blebbistatin, a myosin II inhibitor, implying
      myosin II activation in the process. We used a selection of inhibitors and
      observed that myosin II activation is dependent mainly on Ca2+-calmodulin, with
      only a small contribution from Rho kinase. The signalling pathways stimulated by
      antigen include PLC (phospholipase C) and PLD (phospholipase D). Bleb formation
      was dependent on activation of PLC, but not PLD. Primary alcohols, used
      previously as a means to reduce PLD-derived phosphatidic acid, were potent
      inhibitors of membrane blebbing, but a more selective inhibitor of PLD, FIPI (5
      fluoro-2-indolyl des-chlorohalopemide), was without effect. FIPI also did not
      inhibit membrane ruffling or degranulation of mast cells, indicating that
      inhibition by primary alcohols works through an unidentified mechanism rather
      than via diversion of PLD activity as assumed. We also examined the requirement
      for ARF6 (ADP-ribosylation factor 6) and observed that its expression led to an
      increase in bleb size and a further increase was observed with the dominant
      active mutant, ARF6-Q67L. Since ARF6-T27N had no effect on bleb size, we conclude
      that ARF6 needs to be active to regulate the size of the blebs.

PMID- 19845507
TI  - Identification of the key structural motifs involved in HspB8/HspB6-Bag3
      interaction.
AB  - The molecular chaperone HspB8 [Hsp (heat-shock protein) B8] is member of the B
      group of Hsps. These proteins bind to unfolded or misfolded proteins and protect
      them from aggregation. HspB8 has been reported to form a stable molecular complex
      with the chaperone cohort protein Bag3 (Bcl-2-associated athanogene 3). In the
      present study we identify the binding regions in HspB8 and Bag3 crucial for their
      interaction. We present evidence that HspB8 binds to Bag3 through the hydrophobic
      groove formed by its strands beta4 and beta8, a region previously known to be
      responsible for the formation and stability of higher-order oligomers of many
      sHsps (small Hsps). Moreover, we demonstrate that two conserved IPV (Ile-Pro-Val)
      motifs in Bag3 mediate its binding to HspB8 and that deletion of these motifs
      suppresses HspB8 chaperone activity towards mutant Htt43Q (huntingtin exon 1
      fragment with 43 CAG repeats). In addition, we show that Bag3 can bind to the
      molecular chaperone HspB6. The interaction between HspB6 and Bag3 requires the
      same regions that are involved in the HspB8-Bag3 association and HspB6-Bag3
      promotes clearance of aggregated Htt43Q. Our findings suggest that the co
      chaperone Bag3 might prevent the accumulation of denatured proteins by regulating
      sHsp activity and by targeting their substrate proteins for degradation.
      Interestingly, a mutation in one of Bag3 IPV motifs has recently been associated
      with the development of severe dominant childhood muscular dystrophy, suggesting
      a possible important physiological role for HspB-Bag3 complexes in this disease.

PMID- 19845508
TI  - Comparison of the cellular and biochemical properties of Plasmodium falciparum
      choline and ethanolamine kinases.
AB  - The proliferation of the malaria-causing parasite Plasmodium falciparum within
      the erythrocyte is concomitant with massive phosphatidylcholine and
      phosphatidylethanolamine biosynthesis. Based on pharmacological and genetic data,
      de novo biosynthesis pathways of both phospholipids appear to be essential for
      parasite survival. The present study characterizes PfCK (P. falciparum choline
      kinase) and PfEK (P. falciparum ethanolamine kinase), which catalyse the first
      enzymatic steps of these essential metabolic pathways. Recombinant PfCK and PfEK
      were expressed as His6-tagged fusion proteins from overexpressing Escherichia
      coli strains, then purified to homogeneity and characterized. Using murine
      polyclonal antibodies against recombinant kinases, PfCK and PfEK were shown to be
      localized within the parasite cytoplasm. Protein expression levels increased
      during erythrocytic development. PfCK and PfEK appeared to be specific to their
      respective substrates and followed Michaelis-Menten kinetics. The Km value of
      PfCK for choline was 135.3+/-15.5 microM. PfCK was also able to phosphorylate
      ethanolamine with a very low affinity. PfEK was found to be an ethanolamine
      specific kinase (Km=475.7+/-80.2 microM for ethanolamine). The quaternary
      ammonium compound hemicholinium-3 and an ethanolamine analogue, 2-amino-1
      butanol, selectively inhibited PfCK or PfEK. In contrast, the bis-thiazolium
      compound T3, which was designed as a choline analogue and is currently in
      clinical trials for antimalarial treatment, affected PfCK and PfEK activities
      similarly. Inhibition exerted by T3 was competitive for both PfCK and PfEK and
      correlated with the impairment of cellular phosphatidylcholine biosynthesis.
      Comparative analyses of sequences and structures for both kinase types gave
      insights into their specific inhibition profiles and into the dual capacity of T3
      to inhibit both PfCK and PfEK.

PMID- 19845510
TI  - Dining in with BCL-2: new guests at the autophagy table.
AB  - BCL-2 homologues are major regulators of apoptosis and, as such, play an active
      role in the survival of adult neurons following injury. In recent years, these
      proteins have also been associated with the regulation of autophagy, a catabolic
      process involved in the recycling of nutrients upon starvation. Basal levels of
      autophagy are also required to eliminate damaged proteins and organelles. This is
      illustrated by the accumulation of ubiquitin-positive aggregates in cells
      deficient in autophagy and, in the nervous system, this is associated with
      progressive cell loss and signs of neurodegeneration. Given the importance of
      both apoptosis and autophagy for neuronal survival in adult neurons,
      understanding how BCL-2 homologues co-ordinately regulate these processes will
      allow a better understanding of the cellular processes leading to
      neurodegeneration. In the present review, we will discuss the roles of BCL-2
      homologues in the regulation of apoptosis and autophagy, focussing on their
      impact on adult neurons.

PMID- 19845509
TI  - Tissue factor: beyond coagulation in the cardiovascular system.
AB  - TF (tissue factor) is the main trigger of the coagulation cascade; by binding
      Factor VIIa it activates Factor IX and Factor X, thereby resulting in fibrin
      formation. Various stimuli, such as cytokines, growth factors and biogenic
      amines, induce TF expression and activity in vascular cells. Downstream targets
      of these mediators include diverse signalling molecules such as MAPKs (mitogen
      activated protein kinases), PI3K (phosphoinositide 3-kinase) and PKC (protein
      kinase C). In addition, TF can be detected in the bloodstream, known as
      circulating or blood-borne TF. Many cardiovascular risk factors, such as
      hypertension, diabetes, dyslipidaemia and smoking, are associated with increased
      expression of TF. Furthermore, in patients presenting with acute coronary
      syndromes, elevated levels of circulating TF are found. Apart from its role in
      thrombosis, TF has pro-atherogenic properties, as it is involved in neointima
      formation by inducing vascular smooth muscle cell migration. As inhibition of TF
      action appears to be an attractive target for the treatment of cardiovascular
      disease, therapeutic strategies are under investigation to specifically interfere
      with the action of TF or, alternatively, promote the effects of TFPI (TF pathway
      inhibitor).

PMID- 19845511
TI  - [The efficacy of external counterpulsation depending on severity of coronary
      artery lesion].
AB  - The aim of our investigation was to assess the efficacy of enhanced external
      counterpulsation (EECP) in ischemic heart disease (IHD) patients depending on
      previous by-pass surgery. 30 IHD patients (pts) were treated with EECP using
      standard protocol (35 hours, 1 hour each procedure). All patients were divided
      into 2 groups. 1-st group (n=15) - pts after by-pass surgery, 2-nd group (n=15) -
      pts without previous coronary revascularisation. Pts were examined by ECG,
      echocardiography, bicycle test, radionuclide perfusion scintigraphy (SPECT)
      before and after EECP treatment. There was significant decreasing of perfusion
      defect severity for rest SPECT after EECP treatment (64.93+/-13.21 std and
      58.53+/-17.28 std, respectively, p<0.01) and decreasing of size of perfusion
      defects - 26.10+/-15.76% before and 22.63+/-18.54% after EECP (p<0.05). Size and
      severity of perfusion defects estimated by SPECT at stress conditions didn't
      change. After EECP treatment the decreasing of perfusion defect severity (p<0.01)
      was registered in both groups, the decreasing of size of perfusion (p<0.05) -
      only in the 1-st group. In the 1-st group decreasing of perfusion defect severity
      and size of perfusion was more intensive. The efficacy of EECP depends on
      previous coronary revascularization.

PMID- 19845512
TI  - [Results of three year observation of outpatients with clinical manifestations of
      atherothrombosis (analysis of Russian population of REACH registry)].

PMID- 19845513
TI  - [An experience of the use of a fixed atenolol amlodipine combination in real
      clinical practice: results of multicenter Russian study].
AB  - AIM: To assess clinical, hemodynamic efficacy and tolerability of a Fixed
      Atenolol Amlodipine Combination (FAAC) in patients with arterial 1-3 degree
      arterial hypertension as mono- or combination therapy. MATERIAL AND METHODS:
      Antihypertensive efficacy and tolerability of FAAC was investigated in open
      noncomparative study in 22 centers in 17 cities of Russia on 570 patients (246
      men, 324 women) aged 18-65 years (mean 55,53+8,55 years) with 1-3 degree arterial
      hypertension. Methods of control included office blood pressure (BP) measurement,
      24-hour BP monitoring, electrocardiography, control of biochemical parameters,
      assessment of efficacy and tolerability. RESULTS: Achivement of target BP level
      at the background of treatment was noted in 401 patients (70.35%) including 171
      (30%) patients on monotherapy with FAAC and 230 (40,35%) patients on combination
      therapy with FAAC and other antihypertensive drug. After 60 days of monotherapy
      with FAAC according to data of office measurements systolic BP (SBP) decreased
      from 161.90+/-14,51 to 129.96+/-8,76 mm Hg (p<0.01), diastolic BP (DBP) decreased
      from 97.61+/-7.45 to 80.04+/-6.44 mm Hg (<0.01). Significant lowering of heart
      rate from 79.25+/-9.78 to 65.24+/-7.35 bpm (p<0.01) was also noted. After use of
      combination of FAAC with other antihypertensive drugs according to data of office
      measurements SBP decreased from 168.24+/-16,78 to 129.77+/-9.55 mm Hg (p<0.01),
      DBP decreased from 99.66+/-10.03 to 81.36+/-6.51 mm Hg (<0.01). Heart rate
      decreased from 80.79+/-10.51 to 66.09+/-8.37 bpm (p<0.01). According to data of
      24-hour BP monitoring significant lowering of mean 24-hour, diurnal and nocturnal
      systolic and diastolic BP as well as of hypertensive burden were also noted. No
      statistically significant dynamics of laboratory parameters was registered during
      60 days of therapy with Tenochek. Tolerability was good in 94% of patients,
      adverse events with premature withdrawal of the drug took place in 1.4% of
      patients.

PMID- 19845514
TI  - [Prognostic value of plasma levels of N-terminal pro-brain natriuretic peptide
      and proinflammatory cytokines in patients with heart failure of ischemic
      etiology].
AB  - We included 63 patients with chronic heart failure of ischemic origin (32 with
      left ventricular ejection fraction less than 40%) into prospective study with
      average duration of follow-up 27+/-10 months. Relative risk of lethal outcome was
      significantly increased in patients with initial endsystolic left ventricular
      dimension >6.0 m, enddiastolic left ventricular dimension >7.0 m, left atrial
      dimension >5.0 cm, left ventricular ejection fraction <35%, hemoglobin level <120
      g/L, with disturbances of rhythm and conduction, and elevation of plasma levels
      of N-terminal pro-brain natriuretic peptide (NT-proBNP) >1000 mol/ml and
      interleukin-6 >20 g/ml. Relative risk of combined endpoint significantly
      increased at same values of echocardiographical parameters, plasma levels of NT
      proBNP >500 mol/ml and interleukin-6 >10 g/ml.

PMID- 19845515
TI  - [Holter monitoring in healthy children during first days of life].
AB  - Aim of the study was to determine dynamics of main parameters of heart rhythm in
      children during first days of life. Material and methods. We examined 30 healthy
      newborns (14 boys and 16 girls) aged 1-4 days (2,6+/-1,3 days). Criteria of
      inclusion were healthy mother, normal course of pregnancy and delivery,
      gestational age at birth 38-40 weeks, body mass at birth 3200-3600 g; Algar score
      8/9, no cardiovascular abnormalities at physical examination, informed consent of
      parents. On days 1-2 and 4 of life we carried out 12 lead ECG at rest and 24-hour
      Holter monitoring with assessment of heart rate (HR), arrhythmias, dynamics of QT
      interval, HR variability (HRV) using methods "Time Domain" and "deceleration
      (DC)/acceleration capacity (AC)". Results. Average 24-hour HR was 138+/-17
      beats/min, maximal pauses of sinus rhythm - 990 ms. Supraventricular
      extrasystoles (<10/24 hours) were registered in 35%, ventricular extrasystoles
      (<5/24 hours) in 15% of children. Values of HRV were as follows: N 442 (408-72)
      ms; SDNN 52 (43-75) ms; SDNNi 36 (35-61) ms; SDNNi24 (22-37) ms; SSD 14 (10-20)
      ms; NN50% 0,98(0-2,4)%. Analysis of D/ showed the following values: D = +3.43 +/-
      0.54 (2.16-4.14),=-3.65+/-0.65 (from - 2.13 to - 4.38). Analysis of interval QT
      values: average 24-hour QT (QTo) - 293+/-10 (278-308) ms, maximal - 342+/-38 (328
      360) ms; mean 24-hour QT 442+/-14 (428-470) ms; QT 204+/-11 (191-220) ms; QT -
      308+/-17(284-337) ms, sl Q/RR 0.37 (0.304-0.505); intercept QT/RR 126 (92.0
      151.0), correlation coefficient () QT/RR 0.65 (0.56-0.84). On day 4 compared with
      day 1 there were significantly higher values of correlation (r) QT/RR and lower
      values of sl QT/RR. Conclusions. During first days of life children can have
      supraventricular and ventricular extrasystoles (not more than 10 per 24 hours).
      First 24 hours of life are characterized by most pronounced signs of myocardial
      instability according to data of assessment of QT dynamics. HRV parameters of
      healthy newborns are characterized by high level of sympathetic activity,
      symmetry of deceleration capacity/acceleration capacity parameters.

PMID- 19845516
TI  - [Ser49gly polymorphism as predictor of development of hereditary sick sinus node
      syndrome].
AB  - We demonstrated for the first time on clinico-genetic material an association of
      hereditary sick sinus node syndrome (SSNS) with polymorphism of beta
      adrenorecetor gene. We found that heterozygous variant of Ser49gly of beta
      adrenoreceptor gene was significantly more often met in patients with SSNS and
      their healthy relatives than in subjects of control group. In the group of
      patients with SSNS contrary to control group we noted statistically significant
      preponderance of carriers of mutant Gly49 allele of.

PMID- 19845517
TI  - [Pathogenesis of myocardial hypoxia in patients with metabolic syndrome].
AB  - Aims of the study were to determine main pathophysiologic mechanisms of decreased
      exercise tolerance in patients with metabolic syndrome (MS); to prove the state
      of hypoxemia by ergospirometry in patients with MS; to reveal with the help of
      echocardiography lowering of functional activity of the myocardium in MS; to
      confirm by electron microscopic techniques the presence of perivascular and
      interstitial fibrosis and fatty infiltration of the myocardium in patients with
      MS. In the study we have observed 39 patients with MS and 12 healthy individuals.
      We have noted the decrease of peak oxygen consumption and carbon dioxide
      excretion during the ergospirometry at anaerobic threshold in patients with MS.
      Echocardiographic examination has proven the reduction of left ventricular
      ejection fraction and cardiac contractile performance. The electron microscopic
      techniques have shown diffuse-focal interstitial fibrosis, hypertrophy of
      myocardial cells and fatty infiltration of the myocardium.

PMID- 19845518
TI  - [Correction of metabolic disturbances in patients with stable effort angina and
      metabolic syndrome].

PMID- 19845519
TI  - [Symptomless ST-depression during stress test and risk of sudden cardiac death in
      middle aged men: population prospective study].

PMID- 19845520
TI  - [Normal values of temporal parameters of ECG in children according to results of
      clinico-epidemiological study ECG-screening of children and adolescents in
      Russian federation].
AB  - In order to obtain reliable information about time-domain ECG parameters in
      Russian children and to analyse their links with physiological changes the
      Project "ECG screening of children and adolescents of the Russian Federation" was
      carried out in 2003-2008. Time domain ECG parameters were studied in the
      representative sample of 5387 healthy individuals aged 0 to 18 years. In each age
      group, lower and upper limits of the norm for heart rate (HR), P wave, PQ and QRS
      intervals were defined as 2nd and 98th percentiles of their distribution. The
      equivalent limits of QT interval duration were defined as its 5th and 95th
      percentiles. Relationship between time domain parameters of pediatric ECG and HR
      was analyzed as well as relationship of these parameters with sex and age. The
      most important differences from prior pediatric studies completed 30 years ago
      were obtained for the heart rate limits. Among children aged 0 to 3, there was a
      tendency toward lowering of age-specific lower limits and elevation of age
      specific upper limits. At ages older than 3 years, there was a tendency toward
      lowering of both the upper and the lower limits of HR. The newly obtained 2nd
      percentiles of the heart rate were lower than the known lower limits in nearly
      all ages. This indicates the necessity for revision of criteria of bradicardia in
      children. The present study showed that 5th and 95th percentiles of QTc interval
      (Bazett's formula) varied between 340 ms and 465 ms and were not significantly
      dependent on children's age and only for ages under 13 also on sex. Results of
      the study allowed to build age-specific ranges of norm for the time domain ECG
      parameters presented in a tabular form.

PMID- 19845521
TI  - [Protective effect of mitochondrial antioxidant SkQl at cardiac ischemia and
      reperfusion].
AB  - Mitochondria are believed to be both main origin and target of oxidative stress
      in cells. In the present study we used novel mitochondria-targeted antioxidant
      SkQ1 using triphenylphosphonium cation as a driver. The substance was alimentary
      given to rats daily during 3 weeks in varying doses, from 0.5 to 250 mol/kg/day.
      The isolated hearts were perfused by standard procedure, the isovolumic left
      ventricular pressure was recorded. After stabilization period the hearts were
      subjected to 30-min total normothermic ischemia with subsequent 50-min
      reperfusion. Arrhythmic disorders at the onset of reperfusion were significantly
      less pronounced in SkQ1 groups 0.5 and 5 mol/kg, the arrhythmia index for first
      30-min was 1.3+/-0.3 and 1.8+/-0.6, respectively, vs. 5.7+/-1.3 in control
      experiments. By the end of reperfusion a significantly better recovery of heart
      rate was observed in SkQ1 groups 0.5 and 250 mol/kg and that of developed
      pressure - in SkQ1 group 0.5 mol/kg. As a result, a recovery of the double
      product of developed pressure and heart rate by the end of reperfusion was almost
      twice higher in groups SkQ1 0.5 and 250 mol/kg (55+/-5 and 58+/-8%,
      respectively), vs. the control (30+/-4%, p<0.05). Results suggest that the
      protective action of SkQ1 at postischemic reperfusion may be due to increased
      myocardial antioxidant status.

PMID- 19845522
TI  - [Dynamics of depressive disorders, endothelial dysfunction, and phagocytic
      activity of neutrophils in patients with chronic inflammation under influence of
      treatment with tianeptine].

PMID- 19845523
TI  - [Novel biomarkers: adiponectin in contemporary diagnosis of cardiovascular
      diseases].

PMID- 19845524
TI  - [Dabigatran versus Warfarin in patients with atrial fibrillation. Results of the
      RE-LY study].

PMID- 19845525
TI  - [Wolff--Parkinson--White syndrome: classification, clinical manifestations,
      diagnosis, and treatment].
AB  - Main etiological factors, mechanisms of arrhythmogenesis, and classification of
      Wolff-Parkinson-White (WPW) syndrome are presented and clinico
      electrocardiographical and electrophysiological peculiarities of atrioventricular
      reciprocal tachycardia in this syndrome are described. Main diagnostic measures,
      principles of their correct interpretation are specified and principles of
      tactical approach to management of patients are presented. Indications to
      electrophysiological investigation and radiofrequency catheter ablation, physical
      characteristics of radiofrequency action in regions of optimal mapping of
      supplementary atrioventricular junction are discussed. Data of analysis of
      efficacy of pharmacological and interventional approaches to the treatment of
      patients with WPW syndrome are also presented.

PMID- 19845526
TI  - [Thienopyridines in the treatment and prevention of cardiovascular diseases. Part
      II. Clinical pharmacology of clopidogrel].
AB  - In a series of articles the authors consider clinical pharmacology and experience
      of clinical application of blockers of platelet P2Y12 receptors, most well known
      representatives of which ticlopidine and clopidogrel according to chemical
      structure belong to thienopyridine derivatives. In the second communication we
      describe in detail clinical pharmacokinetics and pharmacodynamics of the most
      often used thienopyridine derivative - clopidogrel. We discuss results of
      randomized studies and clinical observations which have shown that
      pharmacokinetics of clopidogrel might vary substantially in dependence of
      polymorphisms of genes responsible for synthesis of P2Y12 receptors of platelets
      or cytochromic isoenzymes P-450 CYP of liver with participation of which
      formation of active metabolite of clopidogrel occurs. Contrary to practically
      healthy people in patients with various forms of ischemic heart disease (IHD)
      concomitant therapy, for instance some statins and calcium antagonists, can
      affect clopidogrel pharmacokinetics. Pharmacodynamics of clopidogrel in patients
      with IHD with acute coronary syndrome or diabetes mellitus or before percutaneous
      coronary interventions (PCI) also differs from that in healthy people, because in
      these patients hyperaggregation of platelets takes place initially and
      antiaggregatory action of clopidogrel is less expressed. In 10-30% of patients
      with IHD partial or complete resistance to antiaggregation action of clopidogrel
      is detected, which according to some observations is combined with elevated risk
      of thrombotic cardiac complications after PCI. Possible causes of resistance to
      clopidogrel and ways of its overcoming are discussed.

PMID- 19845527
TI  - Liver distribution of gammadelta-T-cells in patients with chronic hepatitis of
      different etiology.
AB  - The gammadelta T cells represent a minor unique T-cell subpopulation long been
      considered as innate-like immune cells. They are found in increased numbers in
      tissues from various inflammatory conditions. Their role in chronic hepatitis,
      however, is still discussed controversially. Fresh frozen tissues from 50
      patients (18 cases hepatitis B infection, 25 hepatitis C, three cases with co
      infection of hepatitis B and C and four patients with autoimmune hepatitis) were
      investigated. Immunohistochemistry with primary antibodies detecting alphabeta
      and gammadelta TCR was used to evaluate their incidence and distribution in the
      different histological structures of the liver. The inflammatory infiltrate in
      all cases of chronic hepatitis was dominated by alphabeta T cells and was mainly
      localized in the portal tracts with formation of an interface hepatitis
      (95.3%alphabeta T cells; 4.7%gammadelta T cells). There were neither significant
      differences between inflammatory infiltrate nor the amount or percentage of
      gammadelta T cells between hepatitis B, C or autoimmune hepatitis. No
      accumulation of gammadelta T cells could be observed in cases of chronic
      hepatitis of different etiologies. The immune-mediated phenomena in chronic
      hepatitis are dominated by alphabeta T cells. Thus, the adapted immune system is
      responsible for the inflammatory processes in chronic hepatitis.

PMID- 19845528
TI  - Comparative analysis of antibiotic resistance and phylogenetic group patterns in
      human and porcine urinary tract infectious Escherichia coli.
AB  - Urinary tract infections (UTIs) are one of the most common infectious diseases in
      humans and domestic animals such as pigs. The most frequent infectious agent in
      such infections is Escherichia coli. Virulence characteristics of E. coli UTI
      strains range from highly virulent pyelonephritis strains to relatively benign
      asymptomatic bacteriuria strains. Here we analyse a spectrum of porcine and human
      UTI E. coli strains with respect to their antibiotic resistance patterns and
      their phylogenetic groups, determined by multiplex PCR. The clonal profiles of
      the strains differed profoundly; whereas human strains predominantly belonged to
      clonal types B2 and D, these were not seen among the porcine strains, which all
      belonged to the E. coli clonal groups A and B1. Contrary to the human strains,
      the majority of the porcine strains were multidrug resistant. The distinct
      profiles of the porcine strains suggest selective pressure due to extensive
      antibiotic use.

PMID- 19845529
TI  - E1AF expression is associated with extra-prostatic growth and matrix
      metalloproteinase-7 expression in prostate cancer.
AB  - E1AF is associated with malignant aggressiveness via regulation of matrix
      metalloproteinases (MMPs), which play pivotal roles in invasion through the
      degradation of extracellular matrix of tissues surrounding tumors. However, the
      clinical significance of E1AF and MMPs in patients with prostate cancer is not
      fully understood. We reviewed 50 tissue samples from patients with T2-3N0M0
      prostate cancer who had undergone radical operation. Expression levels of E1AF,
      MMP-1, -3, -7, -9 and -14 were determined semiquantitatively by
      immunohistochemistry. The mean +/- SD percentage of E1AF-stained cancer cells was
      8.56 +/- 5.22, and it was significantly higher (p < 0.001) than the E1AF
      immunostaining index of normal cells (1.17 +/- 0.61). E1AF immunostaining index
      in pT3 (12.74 +/- 4.80) was significantly higher (p < 0.001) than that in pT2
      (5.78 +/- 3.31). Although E1AF expression correlated with that of MMP-7 and MMP-9
      (r = 0.47, p < 0.001 and r = 0.41, p = 0.004, respectively), multivariate
      analysis showed that E1AF correlated with only MMP-7 expression (OR = 5.81, 95%
      CI = 1.27-26.59, p = 0.023). Our results demonstrated that increased expression
      of E1AF is involved in tumor aggression of prostate cancer. This finding may be
      influenced by regulation of MMP-7. We speculate that E1AF is a possible target in
      treatment and prevention of tumor growth in prostate cancer.

PMID- 19845530
TI  - Kinetics and sensitivity of ELISA IgG pertussis antitoxin after infection and
      vaccination with Bordetella pertussis in young children.
AB  - Sera from 96 young children in a vaccine trial were analysed for kinetics of
      ELISA IgG anti-pertussis toxin (anti-PT) after a laboratory-verified pertussis
      infection. The antibody decay curves after infection were biphasic and similar in
      shape to those after vaccination. The change from a rapid to a slower decay after
      the peak occurred about 4-5 months from the first day of cough. In a group of
      children given a two- or a five-component acellular pertussis vaccine the
      proportion of sera above the tentative cut-off values for anti-PT of 20, 50 or
      100 EU/ml 12 months after onset of the infection were 19%, 0% and 0%
      respectively. Corresponding figures for a whole-cell or placebo vaccine group of
      infected children were significantly higher, 73%, 39% and 30%, i.e. the antibody
      decay after infection in young children depends on vaccination status as well as
      on the pertussis vaccine given. In a large group of non-infected children
      vaccinated with the same five-component acellular vaccine 13%, 0% and 0% had sera
      above 20, 50 and 100 EU/ml at 12 months after the third vaccine dose and all were
      below the minimum level of detection 2 years after vaccination. In conclusion,
      knowledge about anti-PT kinetics is essential for the interpretation of
      seroepidemiological data but hardly offers the possibility to establish valid cut
      off values for anti-PT in single sample serology. An option would be to identify
      a grey zone between the positive and negative ends of the distribution for follow
      up testing by a second serum.

PMID- 19845531
TI  - Serologic screening for celiac disease in children: a comparison between
      established assays and tests with deamidated gliadin-derived peptides plus
      conjugates for both IgA and IgG antibodies.
AB  - Selection of patients for diagnostic biopsy concerning celiac disease (CD) is
      mainly guided by the results with serological screening tests like anti-tissue
      transglutaminase (tTG), anti-endomysium (EmA) and anti-gliadin (AGA) IgA. New
      tests using deamidated gliadin-derived peptides (DGP) including both IgA and IgG
      antibodies have been developed, to cover the IgA-deficient sera. In addition, a
      combined IgA and IgG DGP test, with or without human erythrocyte-derived tTG,
      offers possible advantages. In order to explore the screening accuracy of the new
      combination tests sera from 167 children below 3 years of age were assayed.
      Biopsy had been taken in connection with serology in 32 of these children, 24
      with histopathological CD. The results with the DGP and the combined test were
      congruent with the IgA antibody tests for tTG, EmA and AGA, all identifying 21 of
      24 of the CD cases. Two of the CD patients were AGA-IgA positive only (2/24),
      while 2 of 24 sera were AGA-IgA negative but positive in all the other tests.
      These results raises the question whether the modifications of the gliadin
      antigen not only decrease false positivity but also give more false-negative
      results, a major drawback for a screening test for an important disease. Further
      studies have to be undertaken to explore this. Our results also stress that
      serologic screening of CD in children cannot be based on one test only.

PMID- 19845532
TI  - Staphylococcus aureus isolates from blood and anterior nares induce similar
      innate immune responses in endothelial cells.
AB  - To evaluate the possibility to distinguish virulent from non-virulent isolates,
      gene expression in human umbilical vein endothelial cells (HUVEC) induced by
      invasive and colonizing isolates of Staphylococcus aureus was compared. Gene
      expression in HUVEC was analyzed by microarray analysis after 4 h of infection
      with Staphylococcus aureus, isolated from healthy nasal carriers (n = 5) and from
      blood of septic patients (n = 5), to explore possible differences between the
      groups of bacteria in interaction with HUVEC. All isolates were spa-typed to
      disclose strain relatedness. Moreover, the isolates were characterized with DNA
      microarray to determine the presence of virulence genes and to investigate the
      potential genes of importance in HUVEC interaction. The expression of 41 genes
      was up-regulated, and four were down-regulated in HUVEC by all isolates. Most of
      the up-regulated genes encode cytokines, chemokines, interferon-induced proteins,
      proteins regulating apoptosis and cell proliferation. There was no difference in
      the gene expression pattern between HUVEC infected with invasive or colonizing
      isolates. Furthermore, there was no difference in the presence of bacterial
      virulence genes between the two groups. In conclusion, our data indicate that S.
      aureus isolates induce comparable expression patterns in HUVEC, irrespective of
      invasiveness or presence of virulence genes.

PMID- 19845533
TI  - Cyclooxygenase-2 expression and connection with tumor recurrence and
      histopathologic parameters in gastrointestinal stromal tumors.
AB  - Tissue cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin
      synthesis and has been shown to have roles in carcinogenesis and tumor
      progression. Evaluation of COX-2 overexpression in malignancies has been
      performed mostly on tumors of epithelial origin, and little is known about its
      presence in mesenchymal tumors, especially gastrointestinal stromal tumors
      (GIST). COX-2 has been reported to be widely expressed in GIST and has been
      suggested as a potential diagnostic marker. We evaluated the overexpression and
      roles of COX-2 in tumorigenesis in GIST with regard to its relation to prognostic
      parameters and tumor recurrence. We studied the presence of COX-2 expression
      immunohistochemically and its relation to clinicopathologic prognostic variables
      in 41 cases of GIST. COX-2 was overexpressed in 21 (51%) of 41 tumors. The extent
      of overexpression was greater in tumors that recurred after surgical resection.
      COX-2 overexpression was also higher in tumors with coagulative necrosis, high
      mitotic index and an infiltrative pattern of growth. The observation of greater
      COX-2 expression levels in GIST with unfavorable histopathologic variables is
      contrary to previous reports and consistent with the reported roles of COX-2 in
      carcinogenesis of epithelial malignancies.

PMID- 19845534
TI  - PlGF expression in pre-invasive and invasive lesions of uterine cervix is
      associated with angiogenesis and lymphangiogenesis.
AB  - Most vascular endothelial growth factors (VEGF) have been shown to be associated
      with lymphangiogenesis and angiogenesis in various cancers. However, whether
      placental growth factor (PlGF), a rarely mentioned VEGF member, is involved in
      the pathogenesis of uterine cervical lesions remains unclear. To address this
      issue, we examined the relationship between PlGF expression and clinicopathologic
      variables in patients with pre-invasive and invasive lesions of uterine cervix.
      Sixty-two cervical specimens were immunostained with PlGF polyclonal antibody to
      define PlGF expression, and monoclonal antibodies D2-40 and CD34 to evaluate the
      lymphatic vessel density (LVD) and blood vessel density (BVD) of the lesions.
      PlGF mRNA level was detected by RT-PCR in all lesions from fresh tissues. We
      found that the levels of PlGF protein and mRNA expression were related to
      clinical stages (p < 0.05), but not to other clinicopathologic variables. No
      significant difference in PlGF expression was observed between squamous carcinoma
      and adenocarcinoma. Increased LVD and BVD were all associated with advanced
      stages (p < 0.001). Although LVD was strongly correlated with BVD, only high LVD
      was associated with pelvic lymphatic metastasis. Moreover, the level of PlGF
      expression was associated with both BVD(r = 0.715, p < 0.001) and LVD(r = 0.321,
      p < 0.05). Together, our study suggests that PlGF may participate in both tumor
      associated angiogenesis and lymphangiogenesis of cervical carcinogenesis.

PMID- 19845535
TI  - Differential expression of hMLH1 in sporadic human colorectal cancer tumors and
      distant metastases.
AB  - Somatic defects in the mismatch repair system constitute an important pathway in
      colorectal carcinogenesis. We have examined the expression of mismatch repair
      proteins in sporadic stage IV colorectal tumors and their derived metastases.
      Sporadic tumors were further examined for differences in expression between the
      tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and
      hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver
      metastases. In cases with loss of mismatch repair protein expression, lymph node
      metastases were also examined. Clinicopathological parameters and Ki-67 staining
      indexes were evaluated and compared. Four tumors displayed a complete loss of
      hMLH1/hPMS2 expression at the transition zone; however, three of these expressed
      both proteins at the invasive front and in liver and lymph node metastases. A
      further four were predominantly hMLH1/hPMS2 negative at the transition zone, but
      with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone.
      All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver
      metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No
      significant difference in the proliferative index was observed for the
      hMLH1/hPMS2-compromised group. In stage IV tumors re-expression of hMLH1/hPMS2
      occurred, leading to different patterns of expression within the primary tumor
      and between tumor and metastases. This may have functional importance for the
      chemosensitivity of metastases compared to the primary tumor.

PMID- 19845536
TI  - Immune hierarchy among HIV-1 CD8+ T cell epitopes delivered by dendritic cells
      depends on MHC-I binding irrespective of mode of loading and immunization in HLA
      A*0201 mice.
AB  - Recent human immunodeficiency virus type 1 (HIV-1) vaccination strategies aim at
      targeting a broad range of cytotoxic T lymphocyte (CTL) epitopes from different
      HIV-1 proteins by immunization with multiple CTL epitopes simultaneously.
      However, this may establish an immune hierarchical response, where the immune
      system responds to only a small number of the epitopes administered. To evaluate
      the feasibility of such vaccine strategies, we used the human leukocyte antigen
      (HLA)-A*0201 transgenic (tg) HHD murine in vivo model and immunized with
      dendritic cells pulsed with seven HIV-1-derived HLA-A*0201 binding CTL epitopes.
      The seven peptides were simultaneously presented on the same dendritic cell (DC)
      or on separate DCs before immunization to one or different lymphoid compartments.
      Data from this study showed that the T-cell response, as measured by cytolytic
      activity and gamma-interferon (IFN-gamma)-producing CD8(+) T cells, mainly
      focused on two of seven administered epitopes. The magnitude of individual T-cell
      responses induced by immunization with multiple peptides correlated with their
      individual immunogenicity that depended on major histocompatibility class I
      binding and was not influenced by mode of loading or mode of immunization. These
      findings may have implications for the design of vaccines based on DCs when using
      multiple epitopes simultaneously.

PMID- 19845537
TI  - Real-time PCR detection of five prevalent bacteria causing acute meningitis.

PMID- 19845538
TI  - In vivo optical properties of melanocytic skin lesions: common nevi, dysplastic
      nevi and malignant melanoma.
AB  - We present an in vivo study of the optical properties of common nevi, dysplastic
      nevi and malignant melanoma skin lesions in human subjects. Reflectance spectra
      were measured on 1379 skin lesions, in the visible and near-infrared spectral
      regions, using a spectral imaging system, in a clinical setting. Analysis of the
      data using a reflectance model revealed differences between the optical
      properties of melanin present in nevi and melanoma lesions. These differences,
      which are in agreement with our previous observations on average reflectance
      spectra, may be potentially useful for the noninvasive characterization of
      pigmented skin lesions and the early diagnosis of melanoma.

PMID- 19845539
TI  - Bacteriorhodopsin O-state photocycle kinetics: a surfactant study.
AB  - The spectroscopy and dynamics of interaction between the O intermediate of
      bacteriorhodopsin (bR) and several surfactants (cetrimonium bromide [CTAB],
      sodium dodecyl sulfate [SDS] and diethylene glycol mono-n-hexyl ether [C6E2])
      were investigated using steady-state UV-VIS spectrometry, circular dichroism
      spectroscopy and time-resolved absorption techniques. The steady-state spectral
      results show that bR can retain its trimeric state without severe damage in the
      molar concentration ratio of C6E2/bR ranging up to 4000. Time-resolved
      observations indicate that the rise and decay rates and transient populations of
      the O state can be increased in the presence of nonionic surfactant C6E2;
      however, these studies indicate the opposite phenomenon in the presence of the
      ionic surfactants CTAB and SDS. The observed 40% enhancement in the transient
      population of the O intermediate state that results from treatment of C6E2 is
      proposed to result from an expanding bR structure, which leads to more effective
      proton pumping efficiency in the photosynthetic system of bR.

PMID- 19845540
TI  - Synchronous fluorescence spectroscopy for the detection and characterization of
      cervical cancers in vitro.
AB  - The objective of this study was to assess the diagnostic potential of synchronous
      fluorescence (SF) spectroscopy (SFS) technique for the detection and
      characterization of normal and different malignancy stages of moderately
      differentiated squamous cell carcinoma (MDSCC), poorly differentiated squamous
      cell carcinoma (PDSCC) cervical tissues. SF spectra were measured from 45
      biopsies from 30 patients in vitro. Characteristic, highly resolved peaks and
      significant spectral differences between normal and MDSCC, PDSCC cervical tissues
      were obtained. Nine potential ratios were calculated and used as input variables
      for a discriminant analysis across different groups. The potentiality of the SFS
      technique was estimated by two discriminant analyses. Discriminant analysis I
      performed across normal and abnormal (including MDSCC and PDSCC) cervical tissues
      classified as 100% both original and the cross-validated grouped cases. In
      discriminant analysis II performed across the three groups, normal, MDSCC and
      PDSCC, 100% of both original and the cross-validated grouped cases were correctly
      classified. Using the SFS technique, one can obtain all the key biochemical
      markers such as tryptophan, collagen, hemoglobin, reduced form of nicotinamide
      adenine dinucleotide and flavin adenine dinucleotide in a single scan and hence
      they can be targeted as tumor markers in the detection of normal from abnormal
      cervical tissues.

PMID- 19845541
TI  - Charge transfer in 1,8-naphthalimide: a combined theoretical and experimental
      approach.
AB  - Photophysics of 1,8-naphthalimide (NAPMD) in different solvents has been
      delineated in this paper. Theoretically calculated bond distance of N-H and C=O
      groups rule out any intramolecular proton transfer in the excited state.
      Concomitant increase in negative charge on O atom compared to N atom and dipole
      moment hints at possible intramolecular charge transfer. Progressive redshift
      with polarity of solvents in emission and absorption spectra also confirms the
      theoretical prediction. Weakening of N-H bond helps hydrogen abstraction and
      anion formation in water with decay time of 2.54 ns through intermolecular proton
      transfer. This was corroborated from the ground state photoexcitation of
      laboratory synthesized anion of NAPMD. Amide hydrolysis in higher pH and excess
      proton availability at low pH are responsible for anion emission quenching. A
      possible electron transfer diminishes phosphorescence at 77 K with changing pH.

PMID- 19845542
TI  - Impact of photodynamic treatment with meso-substituted porphyrin on the
      immunomodulatory capacity of white blood cell-containing red blood cell products.
AB  - After transfusion, the presence of contaminating white blood cells (WBC) in blood
      components may result in either deleterious or positive immunological responses.
      We have previously reported that photodynamic treatment (PDT) with meso
      substituted mono-phenyl-tri-(N-methyl-4-pyridyl)-porphyrin (Tri-P(4)) and red
      light can inactivate pathogens in red blood cell (RBC) products. The present
      study explored the effect of PDT on contaminating WBC in RBC products with
      varying hematocrit (Hct). After PDT, we evaluated adaptive and innate
      immunomodulation through allogeneic and mitogenic stimulation. PDT resulted in
      decreased T-cell proliferation which was more pronounced with lower Hct. Dark
      effect of porphyrin Tri-P(4) was remarkable on antigen-presenting cells affecting
      expression of co-stimulatory molecules CD80/CD86. Finally, cytokine profile after
      PDT revealed a mixed Th1/Th2 type response while surface antigen expression
      supported the development of alternatively activated macrophages (AAM phi or Type
      2 macrophages) instead of dendritic cells. In conclusion, PDT with Tri-P(4)
      altered proliferation, allo-stimulation, cell surface antigen expression and
      cytokine profiles of the cells. These results suggest that PDT may be potentially
      useful in preventing transfusion-associated graft-versus-host disease and
      alloimmunization. It seems worthwhile to further explore PDT-induced
      immunomodulation to optimize conditions which may result in allo-tolerance by AAM
      phi.

PMID- 19845543
TI  - Alterations in skin immune response throughout chronic UVB irradiation-skin
      cancer development and prevention by naproxen.
AB  - Skin exposure to UVB radiation has been reported to produce both a significant
      inflammatory response and marked immunosuppression. This work was aimed to
      evaluate whether the response of murine skin to an acute UVB dose was modified by
      pre-exposure to chronic UVB irradiation and by topical treatment with naproxen, a
      nonsteroidal anti-inflammatory drug. Moreover, the effect of naproxen on the
      incidence of UV-induced skin tumors was studied. Prostaglandin E(2) (PGE(2)) and
      tumor necrosis factor alpha (TNF-alpha) levels were increased 96 h post-UVB in
      acutely irradiated animals and both mediators were modified by topical naproxen
      application-PGE(2) was decreased while TNF-alpha was increased. Such inflammatory
      response was suppressed when mice were chronically irradiated. Naproxen
      application on chronically irradiated mice reduced the incidence of tumor
      lesions. Taken together, our data suggest that chronic UVB irradiation generates
      an immunosuppressive state that prevents skin cells from responding normally to
      an acute irradiation challenge, thus impairing the protective effect of TNF-alpha
      against skin tumor development. Furthermore, reduction in the incidence of tumor
      lesions by naproxen may be due to its ability to increase TNF-alpha levels as
      well as to decrease PGE(2).

PMID- 19845545
TI  - How does chronic sildenafil prevent vascular oxidative stress in insulin
      resistant rats?
AB  - INTRODUCTION: Insulin resistance features both endothelial dysfunction and
      increased oxidative stress. Both disorders are targeted by a chronic treatment
      with sildenafil. However, the mechanism of action by which chronic sildenafil
      exerts its effects on reactive oxygen species sources is still largely unknown.
      AIM: We therefore investigated how chronic sildenafil administration could impact
      vascular endothelial NO and superoxide release in a rat model of insulin
      resistance induced by fructose overload. METHODS: Adult male Wistar rats were fed
      a fructose-enriched diet (fructose-fed rats [FFR]) for 9 weeks. From weeks 6-8,
      sildenafil was administered subcutaneously twice daily (20 mg/kg), followed by a
      1-week washout. MAIN OUTCOME MEASURES: Vascular endothelial NO and superoxide
      release were monitored in vitro in thoracic aortic segments using oxidative
      fluorescence. Specific inhibitors were used to distinguish the respective role of
      the main superoxide-producing systems within the vascular wall (i.e.,
      mitochondrial respiratory chain and NADPH oxidases). The levels of expression of
      eNOS, Akt, and NADPH oxidase subunits were determined in the abdominal aorta.
      RESULTS: Chronic sildenafil administration corrected hyperglycemia,
      hyperinsulinemia, and hypertriglyceridemia in FFR. Moreover, after 9 weeks of
      diet, while global unstimulated aortic endothelial NO and superoxide release were
      unchanged in FFR, the relative contribution of the mitochondrial respiratory
      chain and NADPH oxidases was modified. Chronic sildenafil treatment, even after
      the 1-week washout period, was able to increase endothelial NO release
      independently of Akt-dependent phosphorylation by up-regulating eNOS expression,
      and restored the relative contribution of each superoxide-producing system
      examined, yielding endothelial superoxide release. Finally, in vitro incubation
      of aortic segments with sildenafil markedly decreased the endothelial aortic
      superoxide release. CONCLUSIONS: The present study showed that chronic sildenafil
      produced sustained vascular antioxidant effects in insulin-resistant rats by
      increasing NO release and regulating vascular superoxide release, supporting
      therefore further investigations using chronic sildenafil administration in
      preventing cardiovascular alterations associated with oxidative stress.

PMID- 19845544
TI  - Adenosine deaminase enzyme therapy prevents and reverses the heightened
      cavernosal relaxation in priapism.
AB  - INTRODUCTION: Priapism featured with painful prolonged penile erection is
      dangerous and commonly seen in sickle cell disease (SCD). The preventive
      approaches or effective treatment options for the disorder are limited because of
      poor understanding of its pathogenesis. Recent studies have revealed a novel role
      of excess adenosine in priapism caused by heightened cavernosal relaxation, and
      therefore present an intriguing mechanism-based therapeutic possibility. AIM: The
      aim of this study was to determine the therapeutic effects of adenosine deaminase
      (ADA) enzyme therapy to lower adenosine in priapism. METHODS: Both ADA-deficient
      mice and SCD transgenic (Tg) mice display priapism caused by excessive adenosine.
      Thus, we used these two distinct lines of mouse models of priapism as our
      investigative tools. Specifically, we treated both of these mice with different
      dosages of polyethylene glycol-modified ADA (PEG-ADA) to reduce adenosine levels
      in vivo. At the end points of the experiments, we evaluated the therapeutic
      effects of PEG-ADA treatment by measuring adenosine levels and monitoring the
      cavernosal relaxation. MAIN OUTCOME MEASURES: Adenosine levels in penile tissues
      were measured by high-performance liquid chromatography, and cavernosal
      relaxation was quantified by electrical field stimulation (EFS)-induced corporal
      cavernosal strip (CCS) assays. RESULTS: We found that lowering adenosine levels
      in penile tissues by PEG-ADA treatment from birth in ADA-deficient mice prevented
      the increased EFS-induced CCS relaxation associated with priapism. Intriguingly,
      in both ADA-deficient mice and SCD Tg mice with established priapism, we found
      that normalization of adenosine levels in penile tissues by PEG-ADA treatment
      relieved the heightened EFS-induced cavernosal relaxation in priapism.
      CONCLUSIONS: Our studies have identified that PEG-ADA is a novel, safe, and
      mechanism-based drug to prevent and correct excess adenosine-mediated increased
      cavernosal relaxation seen in two independent priapic animal models, and
      suggested its therapeutic possibility in men suffering from priapism.

PMID- 19845546
TI  - Prevalence of interstitial cystitis in vulvodynia patients detected by bladder
      potassium sensitivity.
AB  - INTRODUCTION: Intravesical potassium sensitivity has been reported in 82% of
      vulvodynia patients, suggesting the bladder generates their pain and indicating
      interstitial cystitis (IC)/painful bladder syndrome deserves greater attention in
      differential diagnosis of vulvodynia. AIMS: The aims of this study were to: (i)
      determine the prevalence of IC as detected by intravesical potassium sensitivity;
      and (ii) survey for urinary, pelvic pain, and sexually associated symptoms in
      patients with vulvodynia. METHODS: Consecutive patients with vulvodynia were
      surveyed for urinary and pelvic pain symptoms using the pelvic pain and
      urgency/frequency (PUF) questionnaire, and tested for abnormal epithelial
      permeability using the potassium sensitivity test (PST). Rates of positive PST
      were determined overall and by PUF score range, and were compared in patients
      with intermittent vs. constant vulvodynia symptoms. MAIN OUTCOME MEASURES:
      Results of intravesical PST. RESULTS: Of 122 vulvodynia patients, 102 (84%) had a
      positive PST and 97 (80%) had urologic symptoms. Of the 87 sexually active
      patients, 81 (93%) reported pain associated with sex. Patients with constant
      (72/87, 83%) vs. intermittent symptoms (30/35, 86%) had no significant difference
      in rates of positive PST. Mean PUF score was 13.2. PUF scores of 3-4 were
      associated with an 86% rate of positive PST; scores 5-9, 44%; 10-14, 84%; 15-19,
      87%; 20-24, 86%; and 25 and above, 100%. CONCLUSION: Most patients with
      vulvodynia have a positive PST and urgency/frequency, indicating pain of bladder
      origin (IC). IC deserves far greater consideration in the differential diagnosis
      of patients with vulvodynia. This represents a dramatic change for the
      gynecologic paradigm of vulvodynia, which in many cases appears to be referred
      pain from the urinary bladder.

PMID- 19845547
TI  - Inhalation device allows novel administration of apomorphine in men with erectile
      dysfunction-efficacy and safety findings.
AB  - INTRODUCTION: Erectile dysfunction (ED) treatment is greatly influenced by
      patient preference, and currently available oral therapies do not meet all
      patients' needs. New therapies and formulations are therefore being investigated.
      AIM: The aim of this article is to assess the clinical efficacy and safety of
      inhaled apomorphine, VR004, in men with mild to severe ED. MAIN OUTCOME MEASURES:
      Efficacy outcomes were the change in the proportion of positive responses to
      sexual encounter profile questions, International Index of Erectile Function
      (IIEF) scores and onset of therapeutic effect. Safety outcomes included a change
      in vital signs at an orthostatic challenge and adverse events (AEs). METHODS: Two
      consecutive, multicenter trials each comprised a 4-week no-treatment period and a
      12-week "at home" treatment period with regular clinic visits. Patients (N = 211
      and N = 389) were randomized to receive one of three set doses of VR004 (100-300
      microg) or matching placebo in each trial. VR004 was administered by a dry-powder
      inhaler at least once a week. RESULTS: Efficacy was generally dose dependent. The
      proportion of per-protocol patients maintaining an erection long enough for
      successful intercourse increased in all VR004 groups vs. placebo. IIEF scores
      were higher in the VR004 groups compared with placebo, and the majority of
      responders achieved an erection within 10 minutes of dosing. The safety profile
      of VR004 was generally similar to that of placebo, and AEs were mild or moderate
      in severity. The incidence of treatment-related AEs was dose dependent. Few
      patients (4%) withdrew because of treatment-related AEs, and the majority of
      these withdrawals occurred on the day of the stringent orthostatic challenge.
      CONCLUSIONS: The VR004 system administers low apomorphine doses that are well
      tolerated without compromising efficacy. This route of administration ensures a
      rapid onset of action and reproducible efficacy and safety profiles. Inhaled
      apomorphine is therefore a potential first-line treatment for ED.

PMID- 19845548
TI  - Sexuality during pregnancy.
AB  - INTRODUCTION: Sexuality is an important part of health and well-being. Sexual
      behavior modifies as pregnancy progresses, influenced by biological,
      psychological, and social factors. AIM: To evaluate changes in sexual perceptions
      and activities during pregnancy and to determine sexual dysfunctions in that
      period. MAIN OUTCOME MEASURES: Sexual perceptions (desire from the partner,
      feelings of attractiveness, and fear of sexual intercourse), sexual activities
      during pregnancy (sexual intercourse frequency, the most frequent sexual
      intercourse trimester, sexual activity during the birth week, type(s) of sexual
      intercourse, changes in sexual satisfaction and desire compared with the pre
      pregnancy period, and changes in sexual intercourse frequency during each
      trimester compared with the pre-pregnancy period), and sexual dysfunctions.
      METHODS: Puerperal women were asked to anonymously complete a self-administered
      and structured questionnaire at the day of discharge from hospital. RESULTS: One
      hundred and eighty-eight women, aged between 17 years and 40 years with a mean
      age of 28.9 years, were analyzed. The first trimester was considered the most
      frequent period of sexual intercourse (44.7%), followed by the second trimester
      (35.6%). Fifty-five percent reported a decrease of sexual activity during the
      third trimester. Fear of sexual intercourse was referred by 23.4% of the women
      questioned. Sexual satisfaction was unchanged in 48.4% of the subjects and
      decreased in 27.7% (P < 0.0001); sexual desire is reported to be unchanged in
      38.8% and decreased in 32.5% (P = 0.196) of the population. Vaginal, oral, anal
      sex, and masturbation were performed by 98.3%, 38.1%, 6.6%, and 20.4% of the
      women, respectively. CONCLUSIONS: We determined in our study that sexual
      satisfaction do not change in pregnancy compared with the pre-pregnancy patterns
      despite a decline of sexual activity during the third trimester. A discussion of
      expected changes in sexuality should be routinely done by the doctor in order to
      improve couples' perception of possible sexual modifications induced by
      pregnancy.

PMID- 19845549
TI  - Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a
      systematic review.
AB  - OBJECTIVES: The objective was to asses the efficacy of lipid emulsion as
      antidotal therapy outside the accepted setting of local anesthetic toxicity.
      METHODS: Literature was accessed through PubMed, OVID (1966-February 2009), and
      EMBASE (1947-February 2009) using the search terms "intravenous" AND ["fat
      emulsion" OR "lipid emulsion" OR "Intralipid"] AND ["toxicity" OR "resuscitation"
      OR "rescue" OR "arrest" OR "antidote"]. Additional author and conference
      publication searches were undertaken. Publications describing the use of lipid
      emulsion as antidotal treatment in animals or humans were included. RESULTS:
      Fourteen animal studies, one human study, and four case reports were identified.
      In animal models, intravenous lipid emulsion (ILE) has resulted in amelioration
      of toxicity associated with cyclic antidepressants, verapamil, propranolol, and
      thiopentone. Administration in human cases has resulted in successful
      resuscitation from combined bupropion/lamotrigine-induced cardiac arrest,
      reversal of sertraline/quetiapine-induced coma, and amelioration of verapamil-
      and beta blocker-induced shock. CONCLUSIONS: Management of overdose with highly
      lipophilic cardiotoxic medications should proceed in accord with established
      antidotal guidelines and early poisons center consultation. Data from animal
      experiments and human cases are limited, but suggestive that ILE may be helpful
      in potentially lethal cardiotoxicity or developed cardiac arrest attributable to
      such agents. Use of lipid emulsion as antidote remains a nascent field warranting
      further preclinical study and systematic reporting of human cases of use.

PMID- 19845550
TI  - Randomized clinical trial of propofol with and without alfentanil for deep
      procedural sedation in the emergency department.
AB  - OBJECTIVES: The objectives were to compare the efficacy, occurrence of adverse
      events, and recovery duration of propofol with and without alfentanil for use in
      procedural sedation in the emergency department (ED). METHODS: This was a
      randomized nonblinded prospective trial of adult patients undergoing procedural
      sedation for painful procedures in the ED. Patients with pain before the
      procedure were given intravenous (IV) morphine sulfate until their pain was
      adequately treated at least 20 minutes before starting the procedure. Patients
      received 1 mg/kg propofol either with or without a supplemental dose of 10 mug/kg
      alfentanil for deep procedural sedation. Doses, vital signs, nasal end-tidal
      CO(2) (ETCO(2)), pulse oximetry, and bispectral electroencephalographic (EEG)
      analysis scores were recorded. Subclinical respiratory depression was defined as
      a change in ETCO(2) of >10 mmHg, an oxygen saturation of <92% at any time, or an
      absent ETCO(2) waveform at any time. Clinical events related to respiratory
      depression were noted during the procedure, including the addition of or increase
      in the flow rate of supplemental oxygen, the use of a bag-valve mask apparatus,
      airway repositioning, or stimulation to induce breathing. After the procedure,
      patients were asked if they experienced pain during the procedure or had recall
      of the procedure. RESULTS: A total of 150 patients were enrolled; 146 underwent
      sedation and were included in the analysis. Seventy-four patients received
      propofol, and 71 received propofol with alfentanil. No clinically significant
      complications were noted. Subclinical respiratory depression was seen in 24/74
      patients in the propofol group and 30/71 patients in the propofol/alfentanil
      group (effect size = 9.8%, 95% CI = -5.8% to 25.5%). Clinical signs of
      respiratory depression included an increase in supplemental oxygen use in 25 of
      the 74 propofol patients and 31 of the 71 propofol/alfentanil patients (effect
      size 9.9%, 95% CI = -5.9% to 25.7%), the use of bag-valve mask apparatus in seven
      patients in the propofol group and 12 in the propofol/alfentanil group (effect
      size = 5.6%, 95% CI = -3.5% to 18.4%), airway repositioning in 13 propofol
      patients and 20 propofol/alfentanil patients (effect size = 10.6%, 95% CI = -3.0%
      to 24.2%), and stimulation to induce breathing in 11 propofol patients and 20
      propofol/alfentanil patients (effect size = 13.3%, 95% CI = 0.1% to 26.5%). The
      total time of the procedure was longer for the alfentanil/propofol group (median
      = 11 minutes, range = 5-22 minutes) than for the propofol group (median = 9
      minutes, range = 1 to 43 minutes; effect size = 1.93 minutes, 95% CI = 0.73 to
      2.58, p = 0.02). Pain during the procedure was reported by 10 of the 74 patients
      in the propofol group and 7 of the 71 patients in the propofol/alfentanil group
      (effect size = 4.5%, 95% CI = -6.8% to 14.1%). Recall of some part of the
      procedure was reported by 12 patients in the propofol group and 9 in the
      propofol/alfentanil group (effect size = 3.5%, 95% CI = -7.9% to 15.0%). All
      procedures were successfully completed. CONCLUSIONS: The use of supplemental
      alfentanil with propofol for procedural sedation did not result in a difference
      in reported pain or recall immediately after the procedure. There was an increase
      in the proportion of patients who required stimulation to induce respiration
      during the procedure in patients who received propofol with supplemental
      alfentanil. The addition of supplemental opioid to procedural sedation with
      propofol does not appear beneficial.

PMID- 19845551
TI  - Reliability and validity of the emergency severity index for pediatric triage.
AB  - OBJECTIVES: The Emergency Severity Index (ESI) triage algorithm is a five-level
      triage acuity tool used by emergency department (ED) triage nurses to rate
      patients from Level 1 (most acute) to Level 5 (least acute). ESI has established
      reliability and validity in an all-age population, but has not been well studied
      for pediatric triage. This study assessed the reliability and validity of the ESI
      for pediatric triage at five sites. METHODS: Interrater reliability was measured
      with weighted kappa for 40 written pediatric case scenarios and 100 actual
      patient triages at each of five research sites (independently rated by both a
      triage nurse and a research nurse). Validity was evaluated with a sample of 200
      patients per site. The ESI ratings were compared with outcomes, including
      hospital admission, resource consumption, and ED length of stay. RESULTS:
      Interrater reliability was 0.77 (95% confidence interval [CI] = 0.76 to 0.78) for
      the scenarios (n = 155 nurses) and 0.57 (95% CI = 0.52 to 0.62) for actual
      patients (n = 498 patients). Inconsistencies in triage were noted for the most
      acute and least acute patients, as well as those less than 1 year of age and
      those with medical (rather than trauma) chief complaints. For the validity cohort
      (n = 1,173 patients), outcomes differed by ESI level, including hospital
      admission, which went from 83% for Level 1 patients to 0% for Level 5 (chi
      square, p < 0.0001). Nurses from dedicated pediatric EDs were 31% less likely to
      undertriage patients than nurses in general EDs (odds ratio [OR] = 0.31, 95% CI =
      0.14 to 0.67). CONCLUSIONS: Reliability of the ESI for pediatric triage is
      moderate. The ESI provides a valid stratification of pediatric patients into five
      distinct groups. We found several areas in which nurses have difficulty triaging
      pediatric patients consistently. The study results are being used to develop
      pediatric-specific ESI educational materials to strengthen reliability and
      validity for pediatric triage.

PMID- 19845552
TI  - Intermethod reliability of real-time versus delayed videotaped evaluation of a
      high-fidelity medical simulation septic shock scenario.
AB  - OBJECTIVES: High-fidelity medical simulation (HFMS) is increasingly utilized in
      resident education and evaluation. No criterion standard of assessing performance
      currently exists. This study compared the intermethod reliability of real-time
      versus videotaped evaluation of HFMS participant performance. METHODS: Twenty
      five emergency medicine residents and one transitional resident participated in a
      septic shock HFMS scenario. Four evaluators assessed the performance of
      participants on technical (26-item yes/no completion) and nontechnical (seven
      item, five-point Likert scale assessment) scorecards. Two evaluators provided
      assessment in real time, and two provided delayed videotape review. After 13
      scenarios, evaluators crossed over and completed the scenarios in the opposite
      method. Real-time evaluations were completed immediately at the end of the
      simulation; videotape reviewers were allowed to review the scenarios with no time
      limit. Agreement between raters was tested using the intraclass correlation
      coefficient (ICC), with Cronbach's alpha used to measure consistency among items
      on the scores on the checklists. RESULTS: Bland-Altman plot analysis of both
      conditions revealed substantial agreement between the real-time and videotaped
      review scores by reviewers. The mean difference between the reviewers was 0.0
      (95% confidence interval [CI] = -3.7 to 3.6) on the technical evaluation and -1.6
      (95% CI = -11.4 to 8.2) on the nontechnical scorecard assessment. Comparison of
      evaluations for the videotape technical scorecard demonstrated a Cronbach's alpha
      of 0.914, with an ICC of 0.842 (95% CI = 0.679 to 0.926), and the real-time
      technical scorecard demonstrated a Cronbach's alpha of 0.899, with an ICC of
      0.817 (95% CI = 0.633 to 0.914), demonstrating excellent intermethod reliability.
      Comparison of evaluations for the videotape nontechnical scorecard demonstrated a
      Cronbach's alpha of 0.888, with an ICC of 0.798 (95% CI = 0.600 to 0.904), and
      the real-time nontechnical scorecard demonstrated a Cronbach's alpha of 0.833,
      with an ICC of 0.714 (95% CI = 0.457 to 0.861), demonstrating substantial
      interrater reliability. The raters were consistent in agreement on performance
      within each level of training, as the analysis of variance demonstrated no
      significant differences between the technical scorecard (p = 0.176) and
      nontechnical scorecard (p = 0.367). CONCLUSIONS: Real-time and videotaped-based
      evaluations of resident performance of both technical and nontechnical skills
      during an HFMS septic shock scenario provided equally reliable methods of
      assessment.

PMID- 19845553
TI  - Asymptomatic hypertension in the emergency department: a matter of critical
      public health importance.
AB  - Asymptomatic hypertension (HTN) is commonly encountered in the emergency
      department (ED), but in most circumstances little is done about it. While many
      factors may contribute to this, the failure to recognize asymptomatic HTN as a
      public health problem is particularly important. Given the established long-term
      consequences of elevated blood pressure (BP), a reconsideration of methods that
      could enhance surveillance and intervention in the ED is needed. In this article,
      we discuss the relevant epidemiology of asymptomatic HTN and present a novel
      approach using a modified version of the Haddon's matrix to systematically
      address the challenges that contribute to ineffective screening and suboptimal
      outcomes.

PMID- 19845554
TI  - Adolescent suicide risk screening in the emergency department.
AB  - OBJECTIVES: Many adolescents who die by suicide have never obtained mental health
      services. In response to this, the National Strategy for Suicide Prevention
      recommends screening for elevated suicide risk in emergency departments (EDs).
      This cross-sectional study was designed to examine 1) the concurrent validity and
      utility of an adolescent suicide risk screen for use in general medical EDs and
      2) the prevalence of positive screens for adolescent males and females using two
      different sets of screening criteria. METHODS: Participants were 298 adolescents
      seeking pediatric or psychiatric emergency services (50% male; 83% white, 16%
      black or African American, 5.4% Hispanic). The inclusion criterion was age 13 to
      17 years. Exclusion criteria were severe cognitive impairment, no parent or legal
      guardian present to provide consent, or abnormal vital signs. Parent or guardian
      consent and adolescent assent were obtained for 61% of consecutively eligible
      adolescents. Elevated risk was defined as 1) Suicidal Ideation Questionnaire
      Junior [SIQ-JR] score of > or =31 or suicide attempt in the past 3 months or 2)
      alcohol abuse plus depression (Alcohol Use Disorders Identification Test-3 [AUDIT
      3] score of > or =3, Reynolds Adolescent Depression Scale-2 [RADS-2] score of >
      or =76). The Beck Hopelessness Scale (BHS) and Problem Oriented Screening
      Instrument for Teenagers (POSIT) were used to ascertain concurrent validity.
      RESULTS: Sixteen percent (n = 48) of adolescents screened positive for elevated
      suicide risk. Within this group, 98% reported severe suicide ideation or a recent
      suicide attempt (46% attempt and ideation, 10% attempt only, 42% ideation only)
      and 27% reported alcohol abuse and depression. Nineteen percent of adolescents
      who screened positive presented for nonpsychiatric reasons. One-third of
      adolescents with positive screens were not receiving any mental health or
      substance use treatment. Demonstrating concurrent validity, the BHS scores of
      adolescents with positive screens and the POSIT scores of those with positive
      screens due to alcohol abuse and depression indicated substantial impairment. The
      addition of alcohol abuse with co-occurring depression as a positive screen
      criterion did not result in improved case identification. Among the subgroup
      screening positive due to depression plus alcohol abuse, all but one (>90%) also
      reported severe suicide ideation and/or a recent suicide attempt. This subgroup
      (approximately 17% of adolescents who screened positive) also reported
      significantly more impulsivity than other adolescents who screened positive.
      CONCLUSIONS: The suicide risk screen showed evidence of concurrent validity. It
      also demonstrated utility in identifying 1) adolescents at elevated risk for
      suicide who presented to the ED with unrelated medical concerns and 2) a subgroup
      of adolescents who may be at highly elevated risk for suicide due to the
      combination of depression, alcohol abuse, suicidality, and impulsivity.

PMID- 19845555
TI  - Validity of the Danish Prostate Symptom Score questionnaire in stroke.
AB  - OBJECTIVE: To determine the content and face validity of the Danish Prostate
      Symptom Score (DAN-PSS-1) questionnaire in stroke patients. MATERIALS AND
      METHODS: Content validity was judged among an expert panel in neuro-urology. The
      judgement was measured by the content validity index (CVI). Face validity was
      indicated in a clinical sample of 482 stroke patients in a hospital-based, cross
      sectional survey. RESULTS: I-CVI was rated >0.78 (range 0.94-1.00) for 75% of
      symptom and bother items corresponding to adequate content validity. The expert
      panel rated the entire DAN-PSS-1 questionnaire highly relevant (S-CVI = 1.00). No
      experts suggested items omitted or improved. The response rate was 84% and face
      validity had an acceptable level of completed response for each symptom items (96
      98%) and bother items (93-96%) indicating that all items were well interpreted.
      CONCLUSION: The DAN-PSS-1 questionnaire appears to be content and face valid for
      measuring lower urinary tract symptoms after stroke.

PMID- 19845556
TI  - Focal clinical and electroencephalographic features in patients with juvenile
      myoclonic epilepsy.
AB  - OBJECTIVE: To identify prevalence and factors associated with occurrence of focal
      clinical and electroencephalogram (EEG) abnormalities in patients with juvenile
      myoclonic epilepsy (JME). MATERIALS AND METHODS: Clinical asymmetries in the
      seizures and focal EEG abnormalities were analyzed in 266 patients with JME.
      RESULTS: All the patients had myoclonic jerks (MJ) and generalized tonic-clonic
      seizures (GTCS); 56 (21%) had absence seizures. Asymmetry in clinical seizures
      was reported in 45 (16.9%) and focal EEG abnormalities were noted in 92 (45.5%)
      patients. Amplitude asymmetry or focal onset of generalized discharges was noted
      in 41 (44.6%) and independent focal EEG abnormalities in 30 (32.6%) patients. A
      statistically significant association was seen with the presence of GTCS and MJ
      (P = 0.007), a family history of epilepsy (P = 0.001) and drug resistance (P =
      0.04) and the occurrence of focal EEG abnormalities. CONCLUSION: Patients with
      JME showed focal clinical and EEG features. These features should not be
      misinterpreted as indicative of partial epilepsy.

PMID- 19845557
TI  - Intersession repeatability of optical coherence tomography measures of retinal
      thickness in early age-related macular degeneration.
AB  - PURPOSE: To determine the intersession repeatability of Stratus optical coherence
      tomography (OCT) measures of retinal thickness in patients with age-related
      macular degeneration (AMD). METHODS: Measurement of retinal thickness was
      performed over four sessions over 12 weeks using a standardized OCT protocol with
      the fast macular thickness map in 67 non-treated eyes of 67 patients with AMD
      enrolled in a clinical trial. The intrapatient standard deviation (S(w) ) and 95%
      coefficient of repeatability (CR) (1.96*?2*S(w)), expressed in MUm and as a
      percentage of mean retinal thickness, were calculated to estimate intersession
      repeatability. RESULTS: The CR was 32 MUm for the average retinal thickness in
      the central 1 mm A1 subfield [95% confidence interval (CI) 31-33 MUm] and 53 MUm
      (95% CI 51-55 MUm) for the centre-point thickness (CPT). When expressed as a
      percentage, the CR was 15% (95% CI 14-16) for the central 1 mm A1 subfield and
      29% (95% CI 27-30) for the CPT measure. CONCLUSION: The average central 1 mm (A1)
      subfield retinal thickness measure shows good intersession repeatability in
      patients with stable, early AMD with poorer repeatability for the CPT measure.
      The results suggest that a change in Stratus OCT retinal thickness of more than
      32 MUm in the central A1 subfield is more indicative of true clinical change in
      these patients.

PMID- 19845558
TI  - The decline in visual acuity in elderly people with healthy eyes or eyes with
      early age-related maculopathy in two Scandinavian population samples.
AB  - PURPOSE: This study aimed to analyse the decline in visual acuity (VA) during
      normal ageing in two Scandinavian population samples of subjects aged >= 70 years
      and to study the age-specific decline in VA in eyes with early age-related
      maculopathy (ARM). METHODS: We carried out a cross-sectional analysis of data
      pertaining to VA in the better eye in one population sample from Oulu (OU),
      Finland (aged 70-82 years) and a second population sample from Gothenburg (GG),
      Sweden (aged 82 or 88 years). The change in VA with age was evaluated in healthy
      eyes (OU, n = 119; GG, n = 40) and in eyes with early ARM (OU-ARM, n = 22; GG
      ARM, n = 114) using linear regression or logistic regression. The results were
      compared with those of previous reports. RESULTS: Our population samples showed a
      significant decrease with age in VA in healthy eyes in subjects aged >= 44 years
      using both statistical models. Comparisons with previous reports demonstrated a
      homogeneity in the decline in VA with age. On average, 0.3 logMAR are lost from
      middle age up to 88 years, presumably as a result of physiological ageing. In
      early ARM, the rate of age-specific decline in VA more than doubled and the
      prevalence of VA < 0.5 markedly increased. CONCLUSIONS: Visual acuity in healthy
      eyes declines with age from middle age onwards. The decrease in VA possibly
      accelerates in subjects aged > 70 years, although no significant evidence for
      this was found. An age-specific decline in VA is shown in eyes with early ARM.
      These results are important for the evaluation of age-specific treatment results.

PMID- 19845560
TI  - Intraocular pressure in keratoconus.
AB  - PURPOSE: This study aimed to investigate intraocular pressure (IOP) measurements
      taken using the dynamic contour tonometer (DCT) and the non-contact tonometer
      (NCT) in subjects with keratoconus. METHODS: Intraocular pressure was measured in
      20 keratoconus subjects and 20 age-matched control subjects using the DCT and NCT
      instruments. Central and off-centre measures were taken with the DCT in order to
      highlight any systematic errors associated with corneal biomechanical factors.
      Measures of anterior and posterior corneal topography and thickness were also
      taken in each subject. RESULTS: No significant difference was found between the
      central and off-centre DCT IOP readings for the keratoconus subjects and age
      matched controls (p > 0.05). The average DCT IOP was 14.2 +/- 1.4 mmHg in the
      keratoconus subjects and 14.2 +/- 1.6 mmHg in the controls. However, the average
      NCT readings differed significantly (p < 0.001) between the keratoconus subjects
      (9.2 +/- 1.5 mmHg) and the controls (12.9 +/- 2.4 mmHg). Intraocular pressure
      measurements taken with the DCT showed no significant (p > 0.05) correlation with
      the severity of keratoconus as determined through measures of corneal topography
      and thickness. Equivalent IOP measurements taken with the NCT correlated
      significantly with certain measures of corneal curvature and thickness in the
      keratoconus population. The difference between DCT and NCT IOP was strongly
      correlated with measures of corneal topography and thickness, with differences
      increasing in more advanced keratoconus. CONCLUSIONS: The measurements obtained
      with the DCT do not appear to be dependent upon corneal factors, unlike those
      taken with the NCT. The presence or severity of keratoconus was not correlated
      with DCT IOP values.

PMID- 19845561
TI  - Detection of virulence factors in Serratia strains isolated from contact lens
      associated corneal ulcers.
AB  - PURPOSE: This paper reports on the microbiological findings pertaining to three
      Serratia isolates from soft contact lens-related corneal ulcers, which represent
      a complication of contact lens wear reported with increasing frequency. METHODS:
      Bacterial identification and antibiotic susceptibility testing were performed
      using the Vitek system. Serratia's ability to form biofilm, produce gelatinase,
      elastase and alkaline protease, and invade human corneal epithelial (HCE) cells
      was investigated. The isolates' susceptibility to the following disinfectants was
      tested: (a) ReNu MultiPlus((r)) , containing polyaminopropyl biguanide 0.0001%;
      (b) Opti-Free Express((r)) , containing polyquaternium-1 0.001% and
      myristamidopropyldimethylamine 0.0005%; (c) Opti-Free Replenish((r)) , containing
      polyquaternium-1 0.001% and myristamidopropyldimethylamine 0.0005%, and (d)
      Oxysept Comfort((r)) , a one-step 3% hydrogen peroxide-catalase system. RESULTS:
      Two Serratia marcescens and one Serratia liquefaciens were identified. All the
      strains were susceptible to aminoglycosides and fluoroquinolones. No isolate
      formed biofilm or significantly invaded HCE cells; all produced alkaline protease
      and gelatinase, but not elastase. Opti-Free Express((r)) and Opti-Free
      Replenish((r)) were active against S. liquefaciens, but failed to kill the S.
      marcescens isolates within the minimum recommended time (6 hours). ReNu
      MultiPlus((r)) needed 6 hours to kill one strain of S. marcescens, which is 2
      hours more than recommended. Conversely, Oxysept Comfort((r)) was always
      effective within the minimum recommended time (6 hours). CONCLUSIONS: The ability
      to produce alkaline protease and gelatinase may play a major role in the
      pathogenesis of contact lens-related Serratia keratitis. Several types of contact
      lens solutions may be ineffective in eradicating Serratia from contaminated
      contact lens cases within the minimum recommended time. Only exposure to Oxysept
      Comfort((r)) was always effective against Serratia in this study.

PMID- 19845562
TI  - Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE
      alleles with susceptibility to age-related macular degeneration in Hungarian
      patients.
AB  - PURPOSE: Recent studies strongly support the role of genetic factors in the
      aetiology of age-related macular degeneration (AMD). We investigated the
      frequency of Tyr402His polymorphism of the complement factor H (CFH) gene,
      Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and
      different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order
      to determine the disease risk conferred by these factors. METHODS: In a case
      control study, we performed clinical and molecular genetic examination of 105 AMD
      patients (48 patients in the early and 57 in the late subgroup) and 95 unrelated
      healthy controls. Detailed patient histories were recorded with the use of a
      questionnaire focusing on known risk factors for AMD. RESULTS: In the early AMD
      subgroup, homozygous CFH, LOC387715 or HTRA1 polymorphisms conferred a 4.9-fold
      (95% confidence interval [CI] 1.7-14.2), 7.4-fold (95% CI 2.1-26.2) or 10.1-fold
      (95% CI 2.5-40.8) risk of disease, respectively. In the late AMD subgroup,
      carriers of two CFH, LOC387715 or HTRA1 risk alleles were at 10.7-fold (95% CI
      3.7-31.0), 11.3-fold (95% CI 3.2-40.4) or 13.5-fold (95% CI 3.3-55.4) greater
      disease risk, respectively. Two CFH and one LOC387715 risk alleles in combination
      conferred a 15.0-fold (95% CI 3.2-71.0) increase in risk, whereas two LOC387715
      risk alleles combined with one CFH risk allele was associated with a 14.0-fold
      (95% CI 2.1-95.1) increased risk for late AMD. ApoE alleles neither increased
      disease risk nor proved to be protective. CONCLUSIONS: The CFH, LOC387715 and
      HTRA1 polymorphisms are strongly associated with the development of AMD in the
      Hungarian population. The association is particularly pronounced when homozygous
      risk alleles are present and in the late stages of the disease.

PMID- 19845563
TI  - Combined retinal and cerebral changes in a pre-eclamptic woman.

PMID- 19845564
TI  - Regression of choroidal metastasis secondary to breast carcinoma with adjuvant
      intravitreal injection of bevacizumab.

PMID- 19845565
TI  - Using diffusion MRI for measuring the temperature of cerebrospinal fluid within
      the lateral ventricles.
AB  - AIM: Hypothermia is often induced to reduce brain injury in newborns, following
      perinatal hypoxic-ischaemic events, and in adults following traumatic brain
      injury, stroke or cardiac arrest. We aimed to devise a method, based on diffusion
      weighted MRI, to measure non-invasively the temperature of the cerebrospinal
      fluid in the lateral ventricles. METHODS: The well-known temperature dependence
      of the water diffusion constant was used for the estimation of temperature. We
      carried out diffusion MRI measurements on a 3T Philips Achieva Scanner involving
      phantoms (filled with water or artificial cerebrospinal fluid while slowly
      cooling from 41 to 32 degrees C) and healthy adult volunteers. RESULTS: The
      estimated temperature of water phantoms followed that measured using a mercury
      thermometer, but the estimates for artificial cerebrospinal fluid were 1.04
      degrees C lower. After correcting for this systematic difference, the estimated
      temperature within the lateral ventricles of volunteers was 39.9 degrees C. Using
      diffusion directions less sensitive to cerebrospinal fluid flow, it was 37.7
      degrees C, which was in agreement with the literature. CONCLUSION: Although
      further improvements are needed, measuring the temperature within the lateral
      ventricles using diffusion MRI is a viable method that may be useful for clinical
      applications. We introduced the method, identified sources of error and offered
      remedies for each.

PMID- 19845566
TI  - Review article: the current management of acute liver failure.
AB  - BACKGROUND: Acute liver failure is a devastating clinical syndrome with a
      persistently high mortality rate despite critical care advances. Orthotopic liver
      transplantation (OLT) is a life-saving treatment in selected cases, but effective
      use of this limited resource requires accurate prognostication because of
      surgical risks and the requirement for subsequent life-long immunosuppression.
      AIM: To review the aetiology of acute liver failure, discuss the evidence behind
      critical care management strategies and examine potential treatment alternatives
      to OLT. METHODS: Literature review using Ovid, PubMed and recent conference
      abstracts. RESULTS: Paracetamol remains the most common aetiology of acute liver
      failure in developed countries, whereas acute viral aetiologies predominate
      elsewhere. Cerebral oedema is a major cause of death, and its prevention and
      prompt recognition are vital components of critical care support, which strives
      to provide multiorgan support and 'buy time' to permit either organ regeneration
      or psychological and physical assessment prior to acquisition of a donor organ.
      Artificial liver support systems do not improve mortality in acute liver failure,
      whilst most other interventions have limited evidence bases to support their use.
      CONCLUSION: Acute liver failure remains a truly challenging condition to manage,
      and requires early recognition and transfer of patients to specialist centres
      providing intensive, multidisciplinary input and, in some cases, OLT.

PMID- 19845567
TI  - Review article: somatostatin analogues in the treatment of gastroenteropancreatic
      neuroendocrine (carcinoid) tumours.
AB  - BACKGROUND: The discovery of somatostatin (SST) and the synthesis of a variety of
      analogues constituted a major therapeutic advance in the treatment of
      gastroenteropancreatic neuroendocrine (carcinoid) tumours (GEP-NETs). They
      currently provide the most efficient treatment to achieve symptomatic relief and
      have recently been demonstrated to inhibit tumour growth. AIM: To review 35 years
      of experience regarding the clinical application and efficacy of SST analogues.
      METHODS: The PubMed database (1972-2009) was searched using somatostatin as a
      search term with combinations of terms including 'treatment'; 'neuroendocrine';
      'carcinoid'; 'tumor'; 'octreotide'; 'lanreotide' and 'pasireotide'. RESULTS: In a
      review of 15 studies including 481 patients, the slow-release formulations
      Sandostatin LAR and Somatuline SR/Autogel achieved symptomatic relief in 74.2%
      (61.9-92.8%) and 67.5% (40.0-100%), biochemical response in 51.4% (31.5-100%) and
      39.0% (17.9-58%), and tumour response in 69.8% (47.0-87.5%) and 64.4% (48.0
      87.0%) respectively. Novel SST analogues like SOM230 (pasireotide) that exhibit
      pan SST receptor activity and analogues with high affinity to specific
      somatostatin receptor (sstr) subtypes may further advance the field, but efficacy
      studies are lacking. CONCLUSION: As more precise understanding of NET cell
      biology evolves and molecular biological tools advance, more accurate
      identification of individual tumours sstr profile will probably facilitate a more
      precise delineation of SST analogue treatment.

PMID- 19845568
TI  - Pancreatic cystic lesions: clinical predictors of malignancy in patients
      undergoing surgery.
AB  - BACKGROUND: Despite advances in cross-sectional imaging and the use of molecular
      markers, distinguishing between benign and malignant cysts remains a clinical
      challenge. AIMS: To identify both preoperative clinical and cyst characteristics
      at the time of EUS that predict malignancy. METHODS: A retrospective analysis was
      performed on consecutive patients with pancreatic cysts who underwent endoscopic
      ultrasound (EUS) and surgical resection from May 1996 to December 2007 at a
      tertiary centre. Clinical history, EUS characteristics, cytology, tumour markers
      and surgical histology were collected. Predictors of malignancy were determined
      by univariate and multivariate analysis using logistic regression. RESULTS: A
      total of 153 patients underwent a EUS and subsequent surgical intervention.Of the
      153 patients, 57 (37%) had a histological diagnosis of malignancy. On univariate
      analysis, older age (P < 0.001), male gender (P = 0.010), jaundice (P = 0.039),
      history of other malignancy (P = 0.036), associated mass in cyst (P = 0.004) and
      malignant cytology (P < 0.001) were found to be associated with malignancy.
      History of pancreatitis (P = 0.008) and endoscopist impression of pseudocyst (P =
      0.001) were found to be associated with benign cysts. Multivariate analysis found
      that only older age [Odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01
      1.08], male gender (OR, 2.26; 95% CI, 1.08-4.73) and malignant cytology (OR,
      6.60; 95% CI, 2.02-21.58) were independent predictors of malignancy. CONCLUSIONS:
      Older age, male gender and malignant cytology from EUS predict malignancy at
      surgical resection. These characteristics may be used to estimate the probability
      of malignancy in a cyst and aid in management.

PMID- 19845569
TI  - Sublingual immunotherapy: adherence based on timing and monitoring control
      visits.

PMID- 19845570
TI  - Development, validity and reliability of the food allergy independent measure
      (FAIM).
AB  - BACKGROUND: The Food Allergy Quality of Life Questionnaire-Child Form, -Teenager
      Form and -Adult Form (FAQLQ-CF, -TF and -AF) have recently been developed. To
      measure construct validity in the FAQLQs, a suitable independent measure was
      needed with which FAQLQ scores could be correlated. However, in food allergy, no
      appropriate independent measure existed, which could be used for this purpose.
      AIMS OF THE STUDY: The aim of this study was to describe the development of a
      Food Allergy Independent Measure Child-Form, -Teenager Form and -Adult Form (FAIM
      CF, -TF and -AF) and to assess their validity and reliability. METHODS: The FAIMs
      were developed using previously established methodology to capture the patients'
      expectation of outcome (EO). Face validity was determined by expert opinion. FAIM
      questions showing no correlation to any potential items in the FAQLQs were
      considered irrelevant and eliminated. To measure test-retest reliability, one
      hundred and one patients were included and completed the FAIM twice with a 10-14
      day interval. The intraclass correlation coefficient (ICC), Lin's concordance
      correlation coefficient (CCC) and Bland-Altman plots were used to assess test
      retest reliability. RESULTS: Six FAIM questions were developed and considered
      relevant for the FAIM-CF and -AF, and five questions were relevant for the FAIM
      TF. The FAIMs showed good reliability with ICCs and CCCs above 0.70 and with mean
      differences all close to zero. CONCLUSIONS: Food allergy independent measures
      were developed for children, adolescents and adults and were shown to be valid,
      relevant and reliable. This supports the suitability of the FAIMs for evaluating
      construct validity.

PMID- 19845571
TI  - Coagulation/fibrinolysis and inflammation markers are associated with disease
      activity in patients with chronic urticaria.
AB  - BACKGROUND: The evaluation of disease severity and activity of chronic urticaria
      (CU) is essential for the adequate treatment of patients. However, there is no
      reliable biomarker for such evaluations. Recently, markers of blood coagulation
      and fibrinolysis have been revealed to be elevated in severe cases of CU. In this
      article, we studied the coagulation/fibrinolysis and inflammation markers and
      their relationship to disease activity in patients with CU. METHODS: Plasma
      fibrin degradation products (FDP), d-dimer and serum C-reactive protein (CRP)
      were measured with the assessment of disease severity and skin reaction to
      autologous serum in 82 patients with CU and 37 patients with acute urticaria,
      idiopathic angioedema (AE) or inducible types of urticaria (IU). RESULTS: The
      levels of FDP in patients with CU were significantly higher than those in
      patients with IU, but no other differences in FDP, d-dimer and CRP were observed
      among patients with different types of urticaria. These markers of patients with
      CU were well correlated with each other and significantly associated with disease
      severity of CU, but not with skin reactions to autologous serum. In 37 patients
      with CU, levels of all these parameters reduced as their disease condition
      improved, while they increased when the disease became aggravated. Regarding FDP,
      this relationship was observed even if FDP concentrations were within normal
      range throughout the study. CONCLUSIONS: The measurement of plasma FDP, d-dimer
      and serum CRP may be useful for the assessment of disease activity of CU.

PMID- 19845572
TI  - Multicentre trial evaluating alveolar NO fraction as a marker of asthma control
      and severity.
AB  - BACKGROUND: Exhaled NO can be partitioned in its bronchial and alveolar sources,
      and the latter may increase in the presence of recent asthmatic symptoms and in
      refractory asthma. The aim of this multicentre prospective study was to assess
      whether alveolar NO fraction and FE(NO) could be associated with the level of
      asthma control and severity both at the time of measurement and in the subsequent
      3 months. METHODS: Asthma patients older than 10 years, nonsmokers, without
      recent exacerbation and under regular treatment, underwent exhaled NO measurement
      at multiple constant flows allowing its partition in alveolar (with correction
      for back-diffusion) and bronchial origins based on a two-compartment model of NO
      exchange; exhaled NO fraction at 50 ml/s (FE(NO,0.05)) was also recorded. On
      inclusion, severity was assessed using the four Global initiative for asthma
      (GINA) classes and control using Asthma Control Questionnaire (ACQ). Participants
      were followed-up for 12 weeks, control being assessed by short-ACQ on 1st, 4th,
      8th and 12th week. RESULTS: Two-hundred patients [107 children and 93 adults,
      median age (25th; 75th percentile) 16 years (12; 38)], 165 receiving inhaled
      corticosteroid, were included in five centres. The two-compartment model was
      valid in 175/200 patients (87.5%). Alveolar NO and FE(NO,0.05) did not correlate
      to control on inclusion or follow-up (either with ACQ /short-ACQ values or their
      changes), nor was influenced by severity classes. Alveolar NO negatively
      correlated to MEF(25-75%) (rho = -0.22, P < 0.01). CONCLUSION: Alveolar and
      exhaled NO fractions are not indexes of control or severity in asthmatic children
      and adults under treatment.

PMID- 19845573
TI  - A case-control study of vitamin D status and asthma in adults.

PMID- 19845574
TI  - Allergen provocation increases TH2-cytokines and FOXP3 expression in the
      asthmatic lung.
AB  - BACKGROUND: Allergic asthma is caused by allergen-specific IgE and T-helper cell
      (Th) type 2 responses towards airborne allergens. The objective of this study was
      to investigate local and systemic regulatory mechanisms in the early asthmatic
      response to bronchial allergen provocation. METHODS: Birch pollen-allergic
      patients with mild asthma (n = 13) and healthy nonallergic controls (n = 14) were
      subjected to bronchoalveolar lavage (BAL) and blood sampling. On patients BAL was
      performed twice: without preceding provocation ('before samples') and 24 h after
      bronchial provocation with birch pollen allergen. Lymphocytes in BAL and
      peripheral blood mononuclear cells (PBMCs) were phenotyped by multi-colour flow
      cytometry and cytokines measured by cytometric bead array. Proliferation and
      secreted cytokines were analysed in allergen-stimulated PBMCs, CD25(+) depleted
      PBMCs and PBMCs with IL-10 neutralizing antibodies. RESULTS: The numbers of
      CD69(+) and FOXP3(+) lymphocytes were higher in BAL after compared with before
      allergen provocation in asthmatic patients. Moreover, allergen provocation
      increased expression of FOXP3 in CD4(+)CD25(bright) cells. The cytokine profile
      in BAL fluid from asthmatics revealed higher levels of IL-5, compared with the
      controls, and an increase in IL-5, IL-6, IL-9 and IL-10 after allergen
      provocation. Pollen allergen stimulated PBMC cultures from asthmatic patients
      produced elevated levels of IL-5 and IL-13 compared with the controls, which were
      not affected by depletion of CD25(+) cells or IL-10 neutralization. CONCLUSION:
      Despite an increase in CD4(+)CD25(bright) cells expressing high levels of FOXP3
      in response to bronchial allergen provocation, asthmatic patients exhibit
      enhanced levels of Th2 cytokines in the lung, which may indicate an inability
      among infiltrating cells to suppress Th2 responses.

PMID- 19845575
TI  - Dietary patterns and adult asthma: population-based case-control study.
AB  - BACKGROUND: Epidemiological studies of diet and asthma have focused on relations
      with intakes of individual nutrients and foods and evidence has been conflicting.
      Few studies have examined associations with dietary patterns. METHODS: We carried
      out a population-based case-control study of asthma in adults aged between 16 and
      50 in South London, UK. Information about usual diet was obtained by food
      frequency questionnaire and we used principal components analysis to define five
      dietary patterns in controls. We used logistic and linear regression, controlling
      for confounders, to relate these patterns to asthma, asthma severity, rhinitis
      and chronic bronchitis in 599 cases and 854 controls. RESULTS: Overall, there was
      weak evidence that a 'vegetarian' dietary pattern was positively associated with
      asthma [adjusted odds ratio comparing top vs bottom quintile of pattern score
      1.43 (95% CI: 0.93-2.20), P trend 0.075], and a 'traditional' pattern (meat and
      vegetables) was negatively associated [OR 0.68 (0.45-1.03), P trend 0.071]. These
      associations were stronger amongst nonsupplement users (P trend 0.030 and 0.001,
      respectively), and the association with the 'vegetarian' pattern was stronger
      amongst whites (P trend 0.008). No associations were observed with asthma
      severity. A 'prudent' dietary pattern (wholemeal bread, fish and vegetables) was
      positively associated with chronic bronchitis [OR 2.61 (1.13-6.05), P trend
      0.025], especially amongst nonsupplement users (P trend 0.002). CONCLUSIONS:
      Overall there were no clear relations between dietary patterns and adult asthma;
      associations in nonsupplement users and whites require confirmation. The finding
      for chronic bronchitis was unexpected and also requires replication.

PMID- 19845576
TI  - Usefulness of basophil activation tests for the diagnosis of IgE-mediated allergy
      to quinolones.

PMID- 19845577
TI  - Thrombophilic factors do not predict outcomes in renal transplant recipients
      under prophylactic acetylsalicylic acid.
AB  - A cohort of recipients of renal transplant after 2000 (N=310) was prospectively
      screened on the day of transplantation and 1 month later for a panel of 11
      thrombophilic factors to assess their effect on posttransplant outcomes. All
      patients received prophylactic acetylsalicylic acid, started before
      transplantation. The rate of thromboembolic events or acute rejection episodes
      during the first posttransplant year (primary composite endpoint) was 16.7% among
      patients free of thrombophilic factor (N=60) and 17.2% in those with >or=1
      thrombophilic factor (N=250) (p>0.99). The incidence of the primary endpoint was
      similar among patients free of thrombophilic factors and those with >or=2
      (N=135), or >or=3 (N=53) factors (16.3% and 15.1% respectively; p=1) and in
      patients who remained thrombophilic at 1 month (15.7%; p=0.84). None of the
      individual thrombophilic factor present at the day of transplantation was
      associated with the primary endpoint. The incidence of cardiovascular events at 1
      year, serum creatinine at 1-year, 4-year actuarial graft and patient survival
      were not influenced by the presence of >or=1 thrombophilic factor at baseline
      (p=NS). In conclusion, the presence of thrombophilic factors does not influence
      thromboembolic events, acute rejection, graft or patient survival in patients
      transplanted after 2000 and receiving prophylactic acetylsalicylic acid.

PMID- 19845578
TI  - Predictors of new-onset diabetes after transplantation: the overlooked
      confounders.

PMID- 19845579
TI  - Mycophenolate mofetil versus azathioprine in organ transplantation.

PMID- 19845580
TI  - Racial and ethnic differences in mortality in children awaiting heart transplant
      in the United States.
AB  - Racial differences in outcomes are well known in children after heart transplant
      (HT) but not in children awaiting HT. We assessed racial and ethnic differences
      in wait-list mortality in children <18 years old listed for primary HT in the
      United States during 1999-2006 using multivariable Cox models. Of 3299 listed
      children, 58% were listed as white, 20% as black, 16% as Hispanic, 3% as Asian
      and 3% were defined as 'Other'. Mortality on the wait-list was 14%, 19%, 21%, 17%
      and 27% for white, black, Hispanic, Asian and Other children, respectively. Black
      (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3, 1.9), Hispanic (HR 1.5,
      CI 1.2, 1.9), Asian (HR, 2.0, CI 1.3, 3.3) and Other children (HR 2.3, CI 1.5,
      3.4) were all at higher risk of wait-list death compared to white children after
      controlling for age, listing status, cardiac diagnosis, hemodyamic support, renal
      function and blood group. After adjusting additionally for medical insurance and
      area household income, the risk remained higher for all minorities. We conclude
      that minority children listed for HT have significantly higher wait-list
      mortality compared to white children. Socioeconomic variables appear to explain a
      small fraction of this increased risk.

PMID- 19845581
TI  - Recurrent idiopathic membranous nephropathy: early diagnosis by protocol biopsies
      and treatment with anti-CD20 monoclonal antibodies.
AB  - Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared
      MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and
      in a current cohort diagnosed by protocol biopsies, we analyzed the progression
      of the disease and we assessed the effects of anti-CD20 antibodies (Rituximab) on
      recurrent MN. The incidence of recurrent MN was similar in the historical (53%)
      and the current cohorts (41%), although in the later the diagnosis was made
      earlier (median, 4[2-21] months vs. 83[6-149], p = 0.002) and the disease was
      clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the
      current cohort had progressive increases in proteinuria. Eight recipients were
      treated with Rituximab after their proteinuria increased from median, 211 mg/day
      (64-4898) at diagnosis to 4489 (898-13 855) (p = 0.038). Twelve months post
      Rituximab, 75% of patients had either partial (PR) or complete remission (CR).
      After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment
      biopsies showed resorption of electron dense immune deposits in 6/7 cases and
      were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis
      of subclinical recurrent MN, which is often progressive. Treatment of recurrent
      MN with Rituximab is promising and should be evaluated in a prospective
      randomized controlled trial.

PMID- 19845582
TI  - Long-term controlled normoglycemia in diabetic non-human primates after
      transplantation with hCD46 transgenic porcine islets.
AB  - Xenotransplantation of porcine islets into diabetic non-human primates is
      characterized by (i) an initial massive graft loss possibly due to the instant
      blood-mediated inflammatory reaction and (ii) the requirement of intensive,
      clinically unfriendly immunosuppressive therapy. We investigated whether the
      transgenic expression of a human complement-regulatory protein (hCD46) on porcine
      islets would improve the outcome of islet xenotransplantation in streptozotocin
      induced diabetic Cynomolgus monkeys. Immunosuppression consisted of
      thymoglobulin, anti-CD154 mAb for costimulation blockade, and mycophenolate
      mofetil. Following the transplantation of islets from wild-type pigs (n = 2) or
      from 1,3-galactosyltransferase gene-knockout pigs (n = 2), islets survived for a
      maximum of only 46 days, as evidenced by return to hyperglycemia and the need for
      exogenous insulin therapy. The transplantation of islets from hCD46 pigs resulted
      in graft survival and insulin-independent normoglycemia in four of five monkeys
      for the 3 months follow-up of the experiment. One normalized recipient, selected
      at random, was followed for >12 months. Inhibition of complement activation by
      the expression of hCD46 on the pig islets did not substantially reduce the
      initial loss of islet mass, rather was effective in limiting antibody-mediated
      rejection. This resulted in a reduced need for immunosuppression to preserve a
      sufficient islet mass to maintain normoglycemia long-term.

PMID- 19845583
TI  - Results of gal-knockout porcine thymokidney xenografts.
AB  - Clinical transplantation for the treatment of end-stage organ disease is limited
      by a shortage of donor organs. Successful xenotransplantation could immediately
      overcome this limitation. The development of homozygous alpha1,3
      galactosyltransferase knockout (GalT-KO) pigs removed hyperacute rejection as the
      major immunologic hurdle to xenotransplantation. Nevertheless, GalT-KO organs
      stimulate robust immunologic responses that are not prevented by
      immunosuppressive drugs. Murine studies show that recipient thymopoiesis in
      thymic xenografts induces xenotolerance. We transplanted life-supporting
      composite thymokidneys (composite thymus and kidneys) prepared in GalT-KO
      miniature swine to baboons in an attempt to induce tolerance in a preclinical
      xenotransplant model. Here, we report the results of seven xenogenic thymokidney
      transplants using a steroid-free immunosuppressive regimen that eliminated whole
      body irradiation in all but one recipient. The regimen resulted in average
      recipient survival of over 50 days. This was associated with donor-specific
      unresponsiveness in vitro and early baboon thymopoiesis in the porcine thymus
      tissue of these grafts, suggesting the development of T-cell tolerance. The
      kidney grafts had no signs of cellular infiltration or deposition of IgG, and no
      grafts were lost due to rejection. These results show that xenogeneic thymus
      transplantation can support early primate thymopoiesis, which in turn may induce
      T-cell tolerance to solid organ xenografts.

PMID- 19845584
TI  - Predictors of having a potential live donor: a prospective cohort study of kidney
      transplant candidates.
AB  - The barriers to live donor transplantation are poorly understood. We performed a
      prospective cohort study of individuals undergoing renal transplant evaluation.
      Participants completed a questionnaire that assessed clinical characteristics as
      well as knowledge and beliefs about transplantation. A participant satisfied the
      primary outcome if anyone contacted the transplant center to be considered as a
      live donor for that participant. The final cohort comprised 203 transplant
      candidates, among whom 80 (39.4%) had a potential donor contact the center and 19
      (9.4%) underwent live donor transplantation. In multivariable logistic
      regression, younger candidates (OR 1.65 per 10 fewer years, p < 0.01) and those
      with annual income >or=US$ 15 000 (OR 4.22, p = 0.03) were more likely to attract
      a potential live donor. Greater self-efficacy, a measure of the participant's
      belief in his or her ability to attract a donor, was a predictor of having a
      potential live donor contact the center (OR 2.73 per point, p < 0.01), while
      knowledge was not (p = 0.56). The lack of association between knowledge and
      having a potential donor suggests that more intensive education of transplant
      candidates will not increase live donor transplantation. On the other hand, self
      efficacy may be an important target in designing interventions to help candidates
      find live donors.

PMID- 19845585
TI  - Regulatory T-cell counter-regulation by innate immunity is a barrier to
      transplantation tolerance.
AB  - Innate immune signals foster adaptive immunity through activation of antigen
      presenting cells. Recent in vitro evidence suggests that innate signaling may
      also contribute to immunity by countering the effects of regulatory T cells (T
      regs), counter-regulation. We present in vivo evidence using a transgenic skin
      allograft model that the function of T-regs is lost in the setting of acute skin
      transplantation but remains intact when grafts were transplanted 1 month prior to
      allow surgery-induced inflammation to abate. Our findings identify T-reg counter
      regulation as a naturally occurring process that accompanies transplantation and
      an important barrier to T-reg-mediated tolerance. Our finding further highlights
      the central role of regulatory cell deactivation in the initiation of the immune
      response.

PMID- 19845587
TI  - Impact of Medicare coverage on disparities in access to simultaneous pancreas and
      kidney transplantation.
AB  - In the setting of disparities in access to simultaneous pancreas and kidney
      transplantation (SPKT), Medicare coverage for this procedure was initiated July
      1999. The impact of this change has not yet been studied. A national cohort of 22
      190 type 1 diabetic candidates aged 18-55 for kidney transplantation (KT) alone
      or SPKT was analyzed. Before Medicare coverage, 57% of Caucasian, 36% of African
      American and 38% of Hispanic type 1 diabetics were registered for SPKT versus KT
      alone. After Medicare coverage, these proportions increased to 68%, 45% and 43%,
      respectively. The overall increase in SPKT registration rate was 27% (95% CI 1.16
      1.38). As expected, the increase was more substantial in patients with Medicare
      primary insurance than those with private insurance (Relative Rate 1.18, 95% CI
      1.09-1.28). However, racial disparities were unaffected by this policy change
      (African American vs. Caucasian: 0.97, 95% CI 0.87-1.09; Hispanic vs. Caucasian:
      0.94, 95% CI 0.78-1.05). Even after Medicare coverage, African Americans and
      Hispanics had almost 30% lower SPKT registration rates than their Caucasian
      counterparts (95% CI 0.66-0.79 and 0.59-0.80, respectively). Medicare coverage
      for SPKT succeeded in increasing access for patients with Medicare, but did not
      affect the substantial racial disparities in access to this procedure.

PMID- 19845588
TI  - Positron emission tomography in clinical islet transplantation.
AB  - The fate of islets in clinical transplantation is unclear. To elude on this
      positron emission tomography combined with computed tomography (PET/CT) was
      performed for 60 min during islet transplantation in five patients receiving six
      transplants. A fraction of the islets (23%) were labeled with 18F
      fluorodeoxyglucose ([(18)F]FDG) and carefully mixed with unlabeled islets just
      prior to intraportal transplantation. The peak radioactivity concentration in the
      liver was found at 19 min after start of islet infusion and corresponded to only
      75% of what was expected, indicating that islets are lost during the
      transplantation procedure. No accumulation of radioactivity was found in the
      lungs. A nonphysiological peak of C-peptide was found in plasma during and
      immediately after transplantation in all subjects. Distribution in the liver was
      heterogeneous with wide variations in location and concentration. Islets found in
      areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32%
      of the graft in different subjects. No side effects attributed to the PET/CT
      procedure were found. Clinical outcome in all patients was comparable to that
      previously observed indicating that the [(18)F]FDG labeling procedure did not
      harm the islets. The technique has potential to be used to assess approaches to
      enhance islet survival and engraftment in clinical transplantation.

PMID- 19845589
TI  - Impaired insulin sensitivity as an underlying mechanism linking hepatitis C and
      posttransplant diabetes mellitus in kidney recipients.
AB  - Aim of this study was to investigate the mechanism/s associating hepatitis C
      virus (HCV) infection and posttransplant diabetes mellitus in kidney recipients.
      Twenty HCV-positive and 22 HCV-negative kidney recipients, 14 HCV-positive
      nontransplant patients and 24 HCV-negative nontransplant (healthy) subjects were
      analyzed. A 3-h intravenous glucose tolerance test was performed; peripheral
      insulin sensitivity was assessed by minimal modeling. Pancreatic insulin
      secretion, hepatic insulin uptake, pancreatic antibodies and proinflammatory
      cytokines in serum (tumor necrosis factor-alpha, intereukin-6, high-sensitive C
      reactive protein) were also assessed. HCV-positive recipients showed a
      significantly lower insulin sensitivity as compared to HCV-negative recipients
      (3.0 +/- 2.1 vs. 4.9 +/- 3.0 min(-1).microU.mL(- 1).10(4), p = 0.02), however,
      insulin secretion and hepatic insulin uptake were not significantly different.
      Pancreatic antibodies were negative in all. HCV status was an independent
      predictor of impaired insulin sensitivity (multivariate analysis, p = 0.008). The
      decrease of insulin sensitivity due to HCV was comparable for transplant and non
      transplant subjects. No significant correlation was found between any of the
      cytokines and insulin sensitivity. Our results suggest that impaired peripheral
      insulin sensitivity is associated with HCV infection irrespective of the
      transplant status, and is the most likely pathogenic mechanism involved in the
      development of type 2 diabetes mellitus associated with HCV infection.

PMID- 19845590
TI  - Breaking down donor-reactive T-cell activation to two steps.

PMID- 19845591
TI  - Detailed outcomes analyses are essential for optimizing kidney utilization
      strategies.

PMID- 19845592
TI  - Nitric oxide ventilation of rat lungs from non-heart-beating donors improves
      posttransplant function.
AB  - Lungs from non-heart-beating donors (NHBDs) would enhance the donor pool. Ex vivo
      perfusion and ventilation of NHBD lungs allows functional assessment and
      treatment. Ventilation of rat NHBD lungs with nitric oxide (NO) during ischemia,
      ex vivo perfusion and after transplant reduced ischemia-reperfusion injury (IRI)
      and improved lung function posttransplant. One hour after death, Sprague-Dawley
      rats were ventilated for another hour with either 60% O2 or 60% O2/40 ppm NO.
      Lungs were then flushed with 20-mL cold Perfadex, stored cold for 1 h, perfused
      in an ex vivo circuit with Steen solution and warmed to 37 degrees C, ventilated
      15 min, perfusion-cooled to 20 degrees C, then flushed with cold Perfadex and
      stored cold. The left lung was transplanted and ventilated separately. Recipients
      were sacrificed after 1 h. NO-ventilation was associated with significantly
      reduced wet:dry weight ratio in the ex vivo circuit, better oxygenation, reduced
      pulmonary vascular resistance, increased lung tissue levels of cGMP, maintained
      endothelial NOS eNOS, and reduced increases in tumor necrosis factor alpha (TNF
      alpha) and inducible nitric oxide synthase (iNOS). NO-ventilation had no effect
      on MAP kinases or NF-kappaB activation. NO administration to NHBDs before and
      after lung retrieval may improve function of lungs from NHBDs.

PMID- 19845593
TI  - Paradoxical functions of B7: CD28 costimulation in a MHC class II-mismatched
      cardiac transplant model.
AB  - Blockade of the B7: CD28 costimulatory pathway has emerged as a promising therapy
      to prevent allograft rejection. However, this pathway has also been demonstrated
      to be important for the generation and maintenance of regulatory T cells. In this
      study, we investigated the role of the B7: CD28 pathway in the 'bm12 into B6' MHC
      class II-mismatched vascularized cardiac transplant model of chronic rejection.
      Allograft rejection was remarkably accelerated in B6 background B7DKO and CD28KO
      recipients compared with B6 wild-type (WT) recipients. Allograft rejection was
      associated with a significantly enhanced Th1/Th2 alloreactivity and marked
      reduction in the ratio of regulatory T cells to CD4(+) effector/memory cells. We
      noted that administration of anti-B7-1 and anti-B7-2 mAb prior to transplantation
      also accelerated allograft rejection. Furthermore, depleting CD25(+) cells in B6
      WT recipients of bm12 hearts prior to transplant also precipitated rejection at a
      similar rate. Neither B7/CD28 deficiency nor CD25 depletion affected graft
      survival in single MHC class I-mismatched (bm1 into B6) recipients. This study
      highlights the paradoxical functions of B7: CD28 costimulation in a MHC class II
      mismatched model, in which the B7: CD28 pathway is demonstrated to be important
      in preventing rejection through the generation and maintenance of Tregs.

PMID- 19845594
TI  - The success of continued steroid avoidance after kidney transplantation in the
      US.
AB  - There has been a significant increase in the use of steroid avoidance regimens as
      initial treatment for kidney transplant recipients. Early results of the
      effectiveness of this strategy has been mixed with certain prospective trials
      indicating increased acute rejection but population-based studies indicating
      similar or better graft survival as compared to steroid maintenance. We conducted
      a retrospective study of national registry data to evaluate risk factors for
      discontinuation of steroid avoidance protocols based on patient characteristics
      and concomitant immunosuppression. We evaluated 84 647 solitary kidney transplant
      recipients in the US with at least 6 months graft survival including 24 218
      initially discharged without maintenance steroids. We utilized logistic models to
      assess risk factors for new initiation of steroids after initial steroid
      avoidance and survival models to describe graft survival for patients after
      return to steroids. The most prominent risk factors for new initiation of
      steroids after deceased donor kidney transplantation included African-American
      race (AOR = 1.32, p < 0.01), retransplants (AOR = 1.81, p < 0.01), highly
      sensitized recipients (AOR = 1.29, p < 0.01), recipients with Medicaid (AOR =
      1.85, p < 0.01), elevated HLA-MM (AOR = 1.26, p < 0.01) and older donor age (AOR
      = 1.19, p < 0.01). Concomitant medications were also significantly associated
      with the propensity to newly initiate steroids. Cumulatively the study suggests
      that both patient characteristics and concomitant medications are strongly
      associated with the success of steroid avoidance immunosuppressive regimens.

PMID- 19845595
TI  - Periostitis secondary to prolonged voriconazole therapy in lung transplant
      recipients.
AB  - We report five cases of possible drug-induced periostitis associated with long
      term use of voriconazole therapy after lung transplantation (LT). The diagnosis
      of periostitis was made by the documentation of bone pain, elevation of serum
      alkaline phosphatase and characteristic findings on radionuclide bone imaging in
      the absence of any identifiable rheumatologic disease. This periostitis appears
      similar to hypertrophic osteoarthopathy (HOA) but does not meet all criteria for
      HOA. In all patients, the symptoms resolved rapidly after discontinuation of
      voriconazole therapy. Awareness of this potential syndrome, which manifests as
      bone pain, elevated serum alkaline phosphatase and a bone scan suggestive of
      periostitis, is necessary in LT recipients on long-term voriconazole.

PMID- 19845596
TI  - The impact of c4d pattern and donor-specific antibody on graft survival in
      recipients requiring indication renal allograft biopsy.
AB  - We examined the pattern of PTC C4d by immunohistochemistry and DSA in 297 kidney
      recipients with indication biopsies, and evaluated their predictive value for
      graft survival. Median biopsy time was 5.1 months posttransplant. Patients were
      followed for 17.9 +/- 9.4 months postbiopsy. An 18.5% had focal and 15.2% had
      diffuse C4d, with comparable graft survival (adjusted graft failure HR: 2.3, p =
      0.001; HR:1.9, p < 0.02, respectively). 31.3% were DSA+, 19.5% class I and 22.9%
      class II DSA. Only those with class II DSA had worse outcome (adjusted HR:2.5, p
      = 0.001 for class II only; HR:2.7, p < 0.001 for class I/II DSA). Among patients
      with <10%C4d, 23.9% had DSA, compared to 68.9% with diffuse staining. For
      patients biopsied in first-year posttransplant presence of DSA, regardless of C4d
      positivity in biopsy, was a poor prognostic factor (adjusted graft failure HR:
      4.2, p < 0.02 for C4d-/DSA+; HR:4.9, p = 0.001 for C4d+/DSA+), unlike those
      biopsied later. We have shown that focal C4d had similar impact on graft survival
      as diffuse pattern. During the first-year posttransplant either class I or II
      DSA, and afterward only class II DSA were associated with worse graft survival.
      DSA was predictive of worse outcome regardless of C4d for patients biopsied in
      first year and only with C4d positivity afterward, supporting the importance of
      assessment of both DSA and C4d pattern in biopsy.

PMID- 19845597
TI  - KDIGO clinical practice guideline for the care of kidney transplant recipients.
AB  - The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice
      guideline on the monitoring, management, and treatment of kidney transplant
      recipients is intended to assist the practitioner caring for adults and children
      after kidney transplantation. The guideline development process followed an
      evidence-based approach, and management recommendations are based on systematic
      reviews of relevant treatment trials. Critical appraisal of the quality of the
      evidence and the strength of recommendations followed the Grades of
      Recommendation Assessment, Development, and Evaluation (GRADE) approach. The
      guideline makes recommendations for immunosuppression, graft monitoring, as well
      as prevention and treatment of infection, cardiovascular disease, malignancy, and
      other complications that are common in kidney transplant recipients, including
      hematological and bone disorders. Limitations of the evidence, especially on the
      lack of definitive clinical outcome trials, are discussed and suggestions are
      provided for future research.

PMID- 19845598
TI  - Genetic structure of Eurasian cattle (Bos taurus) based on microsatellites:
      clarification for their breed classification.
AB  - We pool three previously published data sets and present population genetic
      analyses of microsatellite variation in 48 Bos taurus cattle breeds from a wide
      range of geographical origins in Eurasia, mostly its northern territory. Bayesian
      model-based clustering reveals six distinct clusters: besides a single-population
      cluster of the Yakutian Cattle from Far Eastern Siberia and a cluster of breeds
      characteristic of an early origin, the other four major clusters largely
      correspond to previously defined morphological subgroups of Red Lowland, Lowland
      Black-Pied, Longhorned Dairy and North European Polled cattle breeds. The results
      highlighted past expansion events of the productive breeds such as Danish Red,
      Angeln, Holstein-Friesian and Ayrshire in northern and Eastern Europe. Based on
      genetic assignment of the breeds and the availability of breed information, we
      provide a preliminary classification of the five breeds that were to date
      undefined. Furthermore, in the analysis of molecular variance, despite some
      correspondence between geographical proximity and genetic similarity, the breed
      classification appears to be a better predictor of genetic structure in the
      cattle populations (the among-group variance component: breed classification,
      2.47%, P < 0.001; geographical division, 0.77%, P < 0.001).

PMID- 19845599
TI  - Variation in chicken populations may affect the enzymatic activity of lysozyme.
AB  - The chicken lysozyme gene encodes a hydrolase that has a key role in defence,
      especially in ovo. This gene was resequenced in global chicken populations [red,
      grey, Ceylon and green jungle fowl (JF)] and related bird species. Networks,
      summary statistics and tests of neutrality indicate that although there is
      extensive variation at the gene, little is present at coding sites, with the
      exception of one non-synonymous site. This segregating site and a further fixed
      non-synonymous change between red JF and domestic chicken populations are
      spatially close to the catalytic sites of the enzyme and so might affect its
      activity.

PMID- 19845600
TI  - Introduction to hypoxia and consequences: from molecule to malady.

PMID- 19845601
TI  - Regulation of vascularization by hypoxia-inducible factor 1.
AB  - Vascularization and vascular remodeling represent critical adaptive responses to
      tissue hypoxia that are mediated by hypoxia-inducible factor 1 (HIF-1). In
      patients with peripheral arterial disease, these responses are impaired by aging
      and diabetes, leading to critical limb ischemia and amputation. Intramuscular
      injection of an adenovirus encoding a constitutively active form of the HIF
      1alpha subunit (CA5) increases the recovery of blood flow following femoral
      artery ligation in a mouse model of age-dependent critical limb ischemia.
      Intradermal injection of a plasmid encoding CA5 promotes healing of cutaneous
      wounds in a mouse model of diabetes. In cancer, vascularization is required for
      tumors to grow beyond microscopic size, a process that involves HIF-1-dependent
      production of angiogenic growth factors. Daily treatment of prostate cancer
      xenograft-bearing mice with low-dose anthracycline (doxorubicin or daunorubicin)
      chemotherapy inhibits HIF-1 DNA-binding activity, HIF-1-dependent expression of
      angiogenic growth factors, mobilization of circulating angiogenic cells, and
      tumor vascularization, thereby arresting tumor growth.

PMID- 19845602
TI  - FIH-dependent asparaginyl hydroxylation of ankyrin repeat domain-containing
      proteins.
AB  - Studies on hypoxia-sensitive pathways have identified a series of Fe(II)
      dependent dioxygenases that regulate hypoxia-inducible factor (HIF) by prolyl and
      asparaginyl hydroxylation. The asparaginyl hydroxylase factor inhibiting HIF
      (FIH) targets a conserved asparaginyl residue in the C-terminal transactivation
      domain of HIF-alpha. This modification suppresses HIF transcriptional activity by
      inhibiting co-activator recruitment. Recent work has demonstrated that FIH
      targets an alternative class of substrate. Proteins containing a common
      interaction motif known as the ankyrin repeat domain (ARD) have been shown to be
      efficiently hydroxylated by FIH. This review aims to summarize what is currently
      known regarding ARD hydroxylation, including the kinetics and determinants of FIH
      mediated ARD hydroxylation, the structural and functional consequences of ARD
      hydroxylation, and the potential for cross-talk between ARD proteins and HIF
      signaling.

PMID- 19845603
TI  - From polyps to people: a highly familiar response to hypoxia.
AB  - Obligate aerobes, by definition, require oxygen in order to sustain life.
      Therefore, changes in environment or physiology that cause metabolic demand for
      oxygen to exceed supply (hypoxia) can be highly detrimental. Despite considerable
      variation in physiology and habitat between species, a majority of metazoa employ
      homologues of the hypoxia-inducible factor (HIF) transcription factors to adapt
      to oxygen deprivation. Studies in mammals, Drosophila and C. elegans have shown
      that regulation of HIF-alpha by prolyl hydroxylase (PHD)-mediated proteasomal
      degradation is conserved, as are a number of HIF target genes. More recently,
      analysis of coral and beetle HIFs has revealed that, unlike flies and worms, the
      C-terminal transactivation domain of HIF-alpha and its regulatory hydroxylase FIH
      1 are also preserved. The reasons for variable conservation of this system are
      unknown. However, discovery of the "intermediary" properties of the beetle HIF
      pathway may prove a useful tool to better define HIF signaling in both mammals
      and invertebrates.

PMID- 19845605
TI  - Survival in acute and severe low o environment: use of a genetic model system.
AB  - Hypoxia whether present during physiologic states (e.g., embryogenesis) or during
      pathologic states (e.g., obstructive sleep apnea and sickle cell anemia),
      challenges the vertebrate or invertebrate organism. Clearly, hypoxia can lead to
      sublethal cell injury or death and consequently organ or systemic injury and
      failure, depending on severity. We discovered that the adult Drosophila
      melanogaster is tolerant to a low O(2) environment, withstanding approximately 3
      4 hours of total O(2) deprivation or anoxia without showing any evidence of cell
      injury. This opened major avenues for us since the Drosophila has been used so
      effectively in so many relevant research areas. We investigated the changes in
      gene expression in D. melanogaster after severe (1% O(2)) intermittent or
      constant hypoxia treatment for 2.5 hours. Our microarray analysis has identified
      multiple gene families that are up- or downregulated in response to acute
      constant (CH) and intermittent hypoxia (IH). We observed that even for short-term
      the gene expression response to IH and CH varied not only in the number of genes
      but also type of gene families. Furthermore, by utilizing powerful Drosophila
      genetic tools we studied the role of single genes (up- or downregulated in
      arrays) in survival under either paradigm in adult flies. We observed significant
      increased adult survival (as compared to controls) of P-element lines for Hsp70
      and Hsp23 genes during CH and Mdr49 and l (2)08717 genes during IH. This suggests
      that the increased transcript levels as observed in array data after either
      paradigm play an important role under severe hypoxia. Indeed, we found for
      example that over-expressing Hsp70 in vivo in specific fly organs (such as heart)
      significantly increased adult survival during CH as compared to controls. These
      data provide further clues about the mechanisms by which intermittent and
      constant hypoxia lead to cell injury and morbidity or adaptation and survival.

PMID- 19845604
TI  - Maintaining Mammalian iron and oxygen homeostasis: sensors, regulation, and cross
      talk.
AB  - Though iron and oxygen are required to sustain essential biological processes, an
      excess of either can result in oxidative stress. Therefore, mammals tightly
      regulate cellular and systemic iron and oxygen homeostasis. At the cellular
      level, the hypoxia-inducible transcription factors (HIFs) are key mediators of
      oxygen homeostasis through their regulation of genes involved in anaerobic
      metabolism and oxygen delivery, among others. Iron regulatory proteins (IRPs)
      largely govern cellular iron homeostasis through their effects on the translation
      and stability of mRNAs involved in iron uptake, utilization, export, and storage.
      Here, we describe regulatory factors for each pathway that sense both iron and
      oxygen availability and coordinate the maintenance of mammalian iron and oxygen
      homeostasis at both the cellular and systemic levels.

PMID- 19845606
TI  - Mitochondria and hypoxic signaling: a new view.
AB  - Eukaryotic cells respond to low oxygen concentrations by upregulating hypoxic and
      downregulating aerobic nuclear genes (hypoxic signaling). Most of the oxygen
      regulated genes in yeast require the mitochondrial respiratory chain for their up
      or downregulation when cells experience hypoxia. Although it was shown
      previously that the mitochondrial respiratory chain is required for the
      upregulation of some hypoxic genes in both yeast and mammalian cells, its
      underlying role in this process has been unclear. Recently, we have reported that
      mitochondria produce nitric oxide (NO(*)) when oxygen becomes limiting. This
      NO(*) production is nitrite (NO(2) (-))-dependent, requires an electron donor,
      and is carried out by cytochrome c oxidase in a pH-dependent fashion. We call
      this activity Cco/NO(*) and incorporate it into a new model for hypoxic
      signaling. In addition, we have found that some of the NO(*) produced by
      Cco/NO(*) is released from cells, raising the possibility that mitochondrially
      generated NO(*) also functions in extracellular hypoxic signaling pathways.

PMID- 19845607
TI  - Pathophysiological Consequences of HIF Activation: HIF as a modulator of
      fibrosis.
AB  - Tissue fibrosis is associated with structural and functional changes that limit
      blood flow and oxygen availability. In the kidney, tubulointerstitial fibrosis,
      which leads to progressive destruction of renal tissue and irreversible loss of
      kidney function, is associated with reduced tissue oxygen levels and activation
      of hypoxia-inducible factor (HIF) signaling. Although cytoprotective in acute
      injury models, HIF-1 was found to promote fibrosis in an experimental model of
      chronic renal injury following unilateral ureteral obstruction. Pharmacological
      inhibition of lysyl oxidases phenocopied the effects of genetic HIF-1 ablation on
      cell motility in vitro and on fibrogenesis in vivo, suggesting that lysyl
      oxidases are important mediators of profibrotic HIF signaling. These findings
      support the notion that HIF-mediated cellular responses differ under conditions
      of acute and chronic oxygen deprivation. Under certain conditions, these
      responses may lead to further tissue destruction by promoting fibrogenesis.

PMID- 19845608
TI  - Mitochondrial metabolism and cancer.
AB  - Historically, it has been assumed that glycolytic metabolism, not mitochondrial
      metabolism, is essential for tumor cell proliferation. However, most tumor cells
      have functional mitochondria, and recent studies suggest that the citric acid
      cycle (TCA) cycle intermediates are precursors for synthesis of nucleotides,
      lipids, and amino acids. Here we review the accumulating evidence that
      mitochondrial metabolism plays an essential role in tumor cell proliferation.

PMID- 19845609
TI  - Molecular imaging: into in vivo interaction of HIF-1alpha and HIF-2alpha with
      ARNT.
AB  - Fluorescence resonance energy transfer (FRET) combined with confocal laser
      microscopy is a powerful tool to analyze protein-protein interaction in vivo. We
      have applied this combination to study the assembly of the hypoxia-inducible
      factor (HIF) complex in living cells under hypoxic conditions. In hypoxia, the
      basic helix-loop-helix/Period/ARNT/Single-minded (PAS) proteins HIF-1alpha and
      HIF-2alpha accumulate and are translocated into the nucleus. Here, HIF-1alpha and
      HIF-2alpha dimerize with HIF-1beta, also known as aryl hydrocarbon receptor
      nuclear translocator (ARNT), to form HIF-1/HIF-2 complexes, which control the
      expression of specific target genes. Therefore, a new Java-based analyzing
      program was developed at our institute to calculate the nanometer distance
      between alpha and beta subunits of the transcriptionally active HIF-1/-2 complex
      bound to DNA. Fusion proteins of HIF subunits and variants of green fluorescent
      proteins (cyan and yellow fluorescent proteins) were expressed in living cells
      and protein-protein interactions were imaged in vivo by means of FRET.

PMID- 19845610
TI  - Oxygen-sensitive potassium channels in chemoreceptor cell physiology: making a
      virtue of necessity.
AB  - The characterization of the molecular mechanisms involved in low-oxygen
      chemotransduction has been an active field of research since the first
      description of an oxygen-sensitive K(+) channel in rabbit carotid body (CB)
      chemoreceptor cells. As a result, a large number of components of the
      transduction cascade, from O(2) sensors to O(2)-sensitive ion channels, have been
      found. Although the endpoints of the process are analogous, the heterogeneity of
      the elements involved in the different chemoreceptor tissues precludes a unifying
      theory of hypoxic signaling, and it has been a source of controversy. However,
      when these molecular constituents of the hypoxic cascade are brought back to
      their physiological context, it becomes clear that the diversity of mechanisms is
      necessary to build up an integrated cellular response that demands the concerted
      action of several O(2) sensors and several effectors.

PMID- 19845611
TI  - Ion channel regulation by AMPK: the route of hypoxia-response coupling in
      thecarotid body and pulmonary artery.
AB  - Vital homeostatic mechanisms monitor O2 supply and adjust respiratory and
      circulatory function to meet demand. The pulmonary arteries and carotid bodies
      are key systems in this respect. Hypoxic pulmonary vasoconstriction (HPV) aids
      ventilation-perfusion matching in the lung by diverting blood flow from areas
      with an O2 deficit to those rich in O2, while a fall in arterial pO2 increases
      sensory afferent discharge from the carotid body to elicit corrective changes in
      breathing patterns. We discuss here the new concept that hypoxia, by inhibiting
      oxidative phosphorylation, activates AMP-activated protein kinase (AMPK) leading
      to consequent phosphorylation of target proteins, such as ion channels, which
      initiate pulmonary artery constriction and carotid body activation. Consistent
      with this view, AMPK knockout mice exhibit an impaired ventilatory response to
      hypoxia. Thus, AMPK may be sufficient and necessary for hypoxia-response coupling
      and may regulate O2 and thereby energy (ATP) supply at the whole body as well as
      the cellular level.

PMID- 19845612
TI  - Hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle
      cells.
AB  - Acute hypoxia induces pulmonary vasoconstriction and chronic hypoxia causes
      pulmonary vascular remodeling characterized by significant vascular medial
      hypertrophy. Electromechanical and pharmacomechanical mechanisms are involved in
      regulating pulmonary vasomotor tone, while changes in cytosolic Ca2+
      concentration ([Ca2+](cyt)) are an important signal in regulating contraction and
      proliferation of pulmonary artery smooth muscle cells (PASMC). Hypoxia-induced
      increases in [Ca2+](cyt) are, in part, mediated by selective inhibition of
      voltage-gated K+ (Kv) channels in PASMC. Kv1.5, encoded by the KCNA5 gene, is a
      Kv channel alpha subunit that forms functional homotetrameric and
      heterotetrameric Kv channels in PASMC. Activity of Kv channels contributes to the
      regulation of resting membrane potential. Overexpression of the human KCNA5 gene
      in rat PASMC and other cell types increases whole-cell Kv currents and causes
      membrane hyperpolarization. However, acute hypoxia only reduced Kv currents in
      KCNA5-transfected PASMC. These results provide compelling evidence that Kv1.5 is
      an important hypoxia-sensitive Kv channel in PASMC, contributing to regulation of
      membrane potential and intracellular Ca2+ homeostasis during hypoxia. This
      hypoxia-sensitive mechanism essential for inhibiting Kv1.5 channel activity is
      exclusively present in PASMC.

PMID- 19845613
TI  - Enzyme-linked oxygen sensing by potassium channels.
AB  - The ability of ion channels to respond to an acute perturbation in oxygen tension
      is a widespread phenomenon, which encompasses many of the major ion channel
      families. Integral to the ability of several ion channels to respond to acute
      hypoxic challenge is modulation by upstream enzymatic reactions, suggesting that
      many ion channels sense oxygen via enzyme-linked processes. Several enzyme-linked
      oxygen sensing systems have been proposed, including nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase-dependent production of hydrogen peroxide,
      hemoxygenase-dependent generation of carbon monoxide, adenosine monophosphate
      (AMP) kinase-dependent channel phosphorylation, and src-Lck protein tyrosine
      kinase, via a currently undetermined mechanism. Each of these enzymes has been
      shown to endow specific ion channels with the ability to respond to changes in
      oxygen, with hypoxia exclusively evoking channel inhibition. This article reviews
      these proposed mechanisms and presents new insights into how one system,
      hemeoxygenase-2, confers oxygen sensitivity to large conductance, voltage- and
      calcium-activated potassium channels.

PMID- 19845614
TI  - Oxygen sensing in the carotid body.
AB  - The carotid body (CB) is a neural crest-derived organ whose function is to elicit
      hyperventilation in response to hypoxemia. The CB contains clusters of neuron
      like glomus cells enveloped by glia-like sustentacular cells. CB responsiveness
      to acute hypoxia relies on the inhibition of O2-sensitive K+ channels in glomus
      cells, which leads to depolarization, Ca2+ entry and release of transmitters that
      activate afferent nerve fibers. The molecular mechanisms underlying K+ channel
      modulation by O2 tension are unknown. Putative hypoxia-sensing mechanisms can be
      studied in detail using genetically modified mice in conjunction with a thin
      carotid body slice preparation. We discuss here the role in CB oxygen sensing of
      the hypoxia-inducible factor 1alpha, the mitochondrial complex II subunit D, and
      heme oxygenase 2. In chronic hypoxia the CB grows with increase in glomus cell
      number. We identified CB stem cells of glial lineage, which can differentiate
      into functionally normal glomus cells.

PMID- 19845615
TI  - Regulation of oxygen sensitivity in adrenal chromaffin cells.
AB  - Adrenomedullary chromaffin cells (AMC) possess a direct hypoxia-sensing mechanism
      that promotes a vital catecholamine surge at birth. This mitochondria-dependent
      adaptive mechanism is suppressed postnatally as AMC acquire cholinergic
      innervation, and it is mediated by K+ channel inhibition, membrane
      depolarization, and voltage-gated Ca2+ entry. We hypothesized that nicotinic ACh
      receptor (AChR) activation might contribute to this postnatal loss of O2
      sensitivity. Following in utero nicotinic AChR activation, via maternal
      administration of nicotine bitartrate, hypoxic sensitivity was suppressed in
      neonatal AMC. Similarly, when neonatal AMC or immortalized chromaffin (MAH) cells
      were cultured for approximately 7 d with nicotine base (50 muM), hypoxic
      sensitivity was suppressed. This effect required alpha7 nAChR stimulation, and
      involved upregulation of K(ATP) channels, which are activated during hypoxia.
      Thus, nicotinic AChR activation may contribute to the suppression of hypoxic
      sensitivity in AMC, and this pathway could provide the basis for the loss of
      hypoxia tolerance in the offspring of smoking mothers.

PMID- 19845616
TI  - Oxidative DNA modifications in hypoxic signaling.
AB  - Hypoxia, a fundamental biological stimulus, uses reactive oxygen species (ROS) as
      second messengers. Surprising molecular targets of hypoxia-generated ROS are the
      specific bases within hypoxic response elements (HREs) of the vascular
      endothelial growth factor (VEGF) and other hypoxia-inducible genes. Oxidative
      modifications coincide with the onset of mRNA accumulation and are localized to
      transcriptionally active mononucleosomes. The oxidative base modifications are
      removed, and the base excision DNA repair pathway is likely involved since Ref
      1/Ape1, a transcriptional co-activator and DNA repair enzyme, is critical for
      transcription complex assembly. Mimicking the effect of hypoxia by introducing an
      abasic site in an oligonucleotide-based model of ROS-enhanced VEGF HRE sequence
      flexibility resulted in altered transcription factor binding and engendered more
      robust reporter gene expression. These observations suggest that controlled DNA
      "damage" and repair, mediated by ROS used as second messengers and by the base
      excision pathway of DNA repair, respectively, are important for hypoxia-induced
      transcriptional activation.

PMID- 19845617
TI  - The neuronal control of hypoxic ventilation: erythropoietin and sexual
      dimorphism.
AB  - Using mice, we demonstrated that when oxygen supply is lowered, erythropoietin
      (Epo), the main regulator of red blood cell production, modulates the ventilatory
      response by interacting with central (brainstem) and peripheral (carotid bodies)
      respiratory centers. We showed that enhanced Epo levels in the brainstem
      increased the hypoxic ventilatory response, and that intracerebroventricular
      injection of an Epo antagonist (soluble Epo receptor) abolished the ventilatory
      acclimatization to hypoxia. More recently, we have found that the impact of Epo
      on ventilation occurs in a sex-dependent manner. Keeping in mind that women are
      less susceptible to several respiratory sicknesses and syndromes than men, we
      suggest that Epo plays a key role in sexually-dimorphic hypoxic ventilation.
      Accordingly, we foresee that Epo has a potential therapeutic use as treatment for
      hypoxia-associated ventilatory diseases.

PMID- 19845618
TI  - Intermittent hypoxia-mediated plasticity of acute O2 sensing requires altered red
      ox regulation by HIF-1 and HIF-2.
AB  - This article provides a brief review of recent studies addressing the effects of
      chronic intermittent hypoxia (IH) on acute O2 sensing in carotid bodies (CBs) and
      adrenal medullary chromaffin cells (AMCs) and the underlying mechanisms. Chronic
      IH upregulates hypoxic sensing ability of CBs and AMCs in adults and neonates.
      The effects of IH were reversible in adult rats, whereas that of neonatal IH
      persist into adult life. Reactive oxygen species (ROS) mediate IH-induced changes
      in O2 sensing. Differential regulation of hypoxia-inducible factors 1 and 2 (HIF
      1 and 2) contribute to IH-evoked oxidative stress. HIF-1 activation by IH appears
      to be linked to increased pro-oxidant(s), whereas downregulation of HIF-2 by IH
      is coupled to transcriptional downregulation of antioxidant enzyme(s). Thus, the
      studies with chronic IH suggest novel, hitherto uncharacterized, roles for HIF-1
      and HIF-2 in regulating red-ox status leading to plasticity of O2 sensing in CBs
      and AMCs.

PMID- 19845619
TI  - Hypoxia and neurodegeneration.
AB  - Periods of chronic hypoxia, which can arise from numerous cardiorespiratory
      disorders, predispose individuals to the development of dementias, particularly
      Alzheimer's disease (AD). AD is characterized in part by the increased production
      of amyloid beta peptide (Abeta), which forms the extracellular plaques by which
      the disease can be identified post mortem. Numerous studies have now shown that
      hypoxia, even in vitro, can increase production of Abeta in different cell types.
      Evidence has been produced to indicate hypoxia alters both expression of the
      Abeta precursor, APP, and also the expression of the secretase enzymes, which
      cleave Abeta from APP. Other studies implicate reduced Abeta degradation as a
      possible means by which hypoxia increases Abeta levels. Such variability may be
      attributable to cell-specific responses to hypoxia. Further evidence indicates
      that some, but not all of the cellular adaptations to chronic hypoxia (including
      alteration of Ca(2+) homeostasis) require Abeta formation. However, other aspects
      of hypoxic remodeling of cell function appear to occur independently of this
      process. The molecular and cellular responses to hypoxia contribute to our
      understanding of the clinical association of hypoxia and increased incidence of
      AD. However, it remains to be determined whether inhibition of one or more of the
      effects of hypoxia may be of benefit in arresting the development of this
      neurodegenerative disease.

PMID- 19845620
TI  - The role of NF-kappaB in hypoxia-induced gene expression.
AB  - Hypoxia is a common physiologic and pathophysiologic stimulus that activates the
      expression of genes through oxygen-sensitive transcription factors including the
      hypoxia-inducible factor (HIF) and nuclear factor-kappaB (NF-kappaB). Hypoxia
      dependent gene expression can have important physiologic or pathophysiologic
      consequences for an organism, depending upon the cause of the hypoxic insult.
      Consequently, this pathway represents an attractive therapeutic target in a
      number of disease states. While the mechanism linking hypoxia to the activation
      of HIF has been extensively studied, our understanding of how hypoxia activates
      NF-kappaB is limited. Recent studies have demonstrated that similar oxygen
      sensing mechanisms are employed in conferring oxygen sensitivity to both HIF and
      NF-kappaB-dependent gene expression. Furthermore, there is an extensive degree of
      cross-talk occurring between NF-kappaB and HIF. Investigations into mechanisms of
      hypoxic activation of HIF and NF-kappaB and how these signaling pathways interact
      will uncover new therapeutic modalities in a diverse range of disease states
      where hypoxia is a feature of the microenvironment including cancer, vascular
      disease, and chronic inflammation.

PMID- 19845621
TI  - Role of hypoxia-inducible factors in epigenetic regulation via histone
      demethylases.
AB  - Eukaryotic chromatin is subject to multiple posttranslational histone
      modifications such as acetylation, methylation, phosphorylation, and
      ubiquitination. These various covalent modifications have been proposed to
      constitute a "histone code," playing important roles in the establishment of
      global chromatin environments, transcription, DNA repair, and DNA replication.
      Among these modifications, histone methylation specifies regulatory marks that
      delineate transcriptionally active and inactive chromatin. These histone methyl
      marks were considered irreversible; however, recent identification of site
      specific histone demethylases demonstrates that histone methylation is
      dynamically regulated, which may allow cells to rapidly change chromatin
      conformation to adapt to environmental stresses or intrinsic stimuli. Of major
      interest is the observation that these histone demethylase enzymes, which are in
      the Jumonji gene family, require oxygen to function and, in some cases, are
      induced by hypoxia in an HIFalpha-dependent manner. This provides a new mechanism
      for regulation of the response to hypoxia.

PMID- 19845624
TI  - A perspective on natural genetic engineering and natural genome editing.
      Introduction.

PMID- 19845622
TI  - An essential role of the HIF-1alpha-c-Myc axis in malignant progression.
AB  - Cancer is a disease of genomic aberration. The hypoxic microenvironment is
      believed to promote tumor progression via the induction of genetic instability.
      To understand how hypoxia drives tumor progression, we have shown recently that
      the hypoxia-inducible transcription factor, HIF-1alpha, is critical for
      transcriptional repression of DNA repair genes by a noncanonical mode of action
      referred to as the "HIF-1alpha-c-Myc axis." HIF-1alpha action via the HIF-1alpha
      c-Myc axis is independent of its DNA-binding and transactivation domains; instead
      it requires the PAS-B domain to displace the transcription activator c-Myc from
      the target gene promoter for gene repression. Owing to the functional compromise
      on DNA repair, tumor cells with activated HIF-1alpha-c-Myc axis display
      persistent DNA damage, genetic alterations, and malignant progression. However,
      apoptosis-proficient cells are resistant to such changes. These findings argue
      that the hypoxic microenvironment plays a critical role in driving genetic
      alterations especially in apoptosis-deficient cells for malignant progression.

PMID- 19845625
TI  - Revisiting the central dogma in the 21st century.
AB  - Since the elaboration of the central dogma of molecular biology, our
      understanding of cell function and genome action has benefited from many radical
      discoveries. The discoveries relate to interactive multimolecular execution of
      cell processes, the modular organization of macromolecules and genomes, the
      hierarchical operation of cellular control regimes, and the realization that
      genetic change fundamentally results from DNA biochemistry. These discoveries
      contradict atomistic pre-DNA ideas of genome organization and violate the central
      dogma at multiple points. In place of the earlier mechanistic understanding of
      genomics, molecular biology has led us to an informatic perspective on the role
      of the genome. The informatic viewpoint points towards the development of novel
      concepts about cellular cognition, molecular representations of physiological
      states, genome system architecture, and the algorithmic nature of genome
      expression and genome restructuring in evolution.

PMID- 19845626
TI  - Deconstructing the dogma: a new view of the evolution and genetic programming of
      complex organisms.
AB  - Since the birth of molecular biology it has been generally assumed that most
      genetic information is transacted by proteins, and that RNA plays an intermediary
      role. This led to the subsidiary assumption that the vast tracts of noncoding
      sequences in the genomes of higher organisms are largely nonfunctional, despite
      the fact that they are transcribed. These assumptions have since become articles
      of faith, but they are not necessarily correct. I propose an alternative
      evolutionary history whereby developmental and cognitive complexity has arisen by
      constructing sophisticated RNA-based regulatory networks that interact with
      generic effector complexes to control gene expression patterns and the epigenetic
      trajectories of differentiation and development. Environmental information can
      also be conveyed into this regulatory system via RNA editing, especially in the
      brain. Moreover, the observations that RNA-directed epigenetic changes can be
      inherited raises the intriguing question: has evolution learnt how to learn?

PMID- 19845627
TI  - On the origin of cells and viruses: primordial virus world scenario.
AB  - It is proposed that the precellular stage of biological evolution unraveled
      within networks of inorganic compartments that harbored a diverse mix of virus
      like genetic elements. This stage of evolution might makes up the Last Universal
      Cellular Ancestor (LUCA) that more appropriately could be denoted Last Universal
      Cellular Ancestral State (LUCAS). Such a scenario recapitulates the ideas of J.
      B. S. Haldane sketched in his classic 1928 essay. However, unlike in Haldane's
      day, considerable support for this scenario exits today: lack of homology between
      core DNA replication system components in archaea and bacteria, distinct membrane
      chemistries and enzymes of lipid biosynthesis in archaea and bacteria, spread of
      several viral hallmark genes among diverse groups of viruses, and the extant
      archaeal and bacterial chromosomes appear to be shaped by accretion of diverse,
      smaller replicons. Under the viral model of precellular evolution, the key
      components of cells originated as components of virus-like entities. The two
      surviving types of cellular life forms, archaea and bacteria, might have emerged
      from the LUCAS independently, along with, probably, numerous forms now extinct.

PMID- 19845628
TI  - The great billion-year war between ribosome- and capsid-encoding organisms (cells
      and viruses) as the major source of evolutionary novelties.
AB  - Our conceptions on the origin, nature, and role of viruses have been shaken
      recently by several independent lines of research. There are many reasons to
      believe now that viruses are more ancient than modern cells and have always been
      more abundant and diverse than their cellular targets. Viruses can be defined as
      capsid-encoding organisms that transform their "host" cell into a viral factory.
      If capsid-encoding organisms (viruses) and ribosome-encoding organisms (cells)
      are the major types of living entities on our planet, it seems logical to
      conclude that their conflict has been a major engine of biological evolution (in
      the framework of natural selection). In particular, many novelties first selected
      in the viral world might have been transferred to cells as a consequence of the
      continuous flow of viral genes into cellular genomes. We discuss recent
      observations and hypotheses suggesting that viruses have played a major role at
      different stages of biological evolution, such as the RNA to DNA transition, the
      origin of the eukaryotic nucleus, or, alternatively, the origin of unique
      features in multicellular macrobes.

PMID- 19845629
TI  - Learning from bacteria about natural information processing.
AB  - Under natural growth conditions, bacteria live in complex hierarchical
      communities. To conduct complex cooperative behaviors, bacteria utilize
      sophisticated communication to the extent that their chemical language includes
      semantic and even pragmatic aspects. I describe how complex colony forms
      (patterns) emerge through the communication-based interplay between individual
      bacteria and the colony. Individual cells assume newly co-generated traits and
      abilities that are not prestored in the genetic information of the cells, that
      is, not all the information required for efficient responses to all environmental
      conditions is stored. To solve newly encountered problems, they assess the
      problem via collective sensing, recall stored information of past experience, and
      then execute distributed information processing of the 10(9)-10(12) bacteria in
      the colony--transforming the colony into a "super-brain." I show illuminating
      examples of swarming intelligence of live bacteria in which they solve
      optimization problems that are beyond what human beings can solve. This will lead
      to a discussion about the special nature of bacterial computational principles
      compared to Turing algorithm computational principles, in particular about the
      role of distributed information processing.

PMID- 19845630
TI  - The viral eukaryogenesis hypothesis: a key role for viruses in the emergence of
      eukaryotes from a prokaryotic world environment.
AB  - Understanding how the gulf between prokaryotic and eukaryotic cellular design
      arose is a major challenge. The viral eukaryogenesis (VE) hypothesis addresses
      the challenge of eukaryotic origins by suggesting the first eukaryotic cell was a
      multimember consortium consisting of a viral ancestor of the nucleus, an archaeal
      ancestor of the eukaryotic cytoplasm, and a bacterial ancestor of the
      mitochondria. Using only prokaryotes and their viruses, and invoking selective
      pressures observed in modern organisms, the VE hypothesis can explain the origins
      of the eukaryotic cell, sex, and meiosis. In the VE hypothesis, a cell wall-less
      archaeon and an alpha-proteobacterium established a syntrophic relationship, and
      then a complex DNA virus permanently lysogenized the archaeal syntroph to produce
      a consortium of three organisms that evolved into the eukaryotic cell. The
      mechanisms by which the virus replicated, controlled its copy number, and
      segregated to daughter cells led to the evolution of the asexual mitotic
      replication cycle and the sexual meiotic replication cycle. The VE hypothesis
      conceptually unifies prokaryotic and eukaryotic sex into variants of a single
      process.

PMID- 19845631
TI  - Cell-cell channels, viruses, and evolution: via infection, parasitism, and
      symbiosis toward higher levels of biological complexity.
AB  - Between prokaryotic cells and eukaryotic cells there is dramatic difference in
      complexity which represents a problem for the current version of the cell theory,
      as well as for the current version of evolution theory. In the past few decades,
      the serial endosymbiotic theory of Lynn Margulis has been confirmed. This results
      in a radical departure from our understanding of living systems: the eukaryotic
      cell represents de facto"cells-within-cell." Higher order "cells-within-cell"
      situations are obvious at the eukaryotic cell level in the form of secondary and
      tertiary endosymbiosis, or in the male and female gametophytes of higher plants.
      The next challenge of the current version of the cell theory is represented by
      the fact that the multicellular fungi and plants are, in fact, supracellular
      assemblies as their cells are not physically separated from each other. Moreover,
      there are also examples of alliances and mergings between multicellular
      organisms. Infection, especially the viral one, but also bacterial and fungal
      infections, followed by symbiosis, is proposed to act as the major force that
      drives the biological evolution toward higher complexity.

PMID- 19845632
TI  - Impact of RNA virus infection on plant cell function and evolution.
AB  - Viruses are obligate symbionts that tightly interact with their hosts to complete
      their life cycle. Each infected cell is confronted with the accumulation of viral
      products and activities that have evolved to support the replication and spread
      of the virus in the context of host cell functions and defense responses. Tobacco
      mosaic virus encodes replicase proteins and coat protein, to replicate and
      protect the RNA genome, and a movement protein (MP) that binds viral RNA and
      manipulates the size exclusion limit of plasmodesmata to facilitate the spread of
      the viral genomic RNA (vRNA). The MP and replicase also interfere with the
      cellular RNA silencing machinery that influences plant gene expression and
      development. Moreover, virus-infected cells stimulate the production of a
      systemic signal ahead of the virus front that triggers genomic recombination
      leading to heritable genetic changes. Thus viruses can interact with their hosts
      through diverse molecular interactions. Given the high mutation rate of viruses,
      these interactions have implications for evolutionary processes and adaptations
      at the virus-host interface that may contribute to eukaryotic evolution.

PMID- 19845633
TI  - Hen or egg?: some thoughts on tunneling nanotubes.
AB  - Precise coordination of various cell types and tissues represents a substantial
      prerequisite for the development and maintenance of multicellular organisms.
      Therefore, eukaryotic cells have developed a variety of complex structures,
      including synapses or gap junctions. Recently, thin membranous channels, termed
      "tunnelling nanotubes," were discovered. Tunnelling nanotubes interconnect
      miscellaneous animal cells and are assumed to be involved in important
      physiological and pathological mechanisms, such as the intercellular spread of
      diverse pathogens. This phenomenon shows striking similarities to plant tissues,
      where cells are connected via membranous channels, called plasmodesmata. Emerging
      evidence suggests that the discovery of tunnelling nanotubes may enforce
      reconsideration of previous conceptions of intercellular communication,
      additionally providing novel perspectives concerning early evolution of
      multicellular life-forms.

PMID- 19845634
TI  - Evolution of genes and organisms: the tree/web of life in light of horizontal
      gene transfer.
AB  - Gene exchange necessitates expanding the model of the tree of life, impacts the
      notion of organismal and molecular most recent common ancestors, and provides
      examples of natural selection working at multiple levels. Gene exchange, whether
      by horizontal gene transfer (HGT), hybridization of species, or symbiosis,
      modifies the organismal tree of life into a web. Darwin suggested the tree of
      life was like a coral, where living surface branches were supported by masses of
      dead branches. In phylogenetic trees, organismal or molecular lineages coalesce
      back to a lucky universal ancestor whose descendents are found in current
      lineages and which coexisted with other, now-extinct lineages. HGT complicates
      the reconstruction of a universal ancestor; genes in a genome can have different
      evolutionary histories, and even infrequent gene transfer will cause different
      molecular lineages to coalesce to molecular ancestors that existed in different
      organismal lineages and at different times. HGT, as well as symbiosis, provides a
      mechanism for integrating and expanding the organizational level on which natural
      selection acts, contributing to selection at the group and community level.

PMID- 19845635
TI  - The natural genetic engineering of polydnaviruses.
AB  - The polydnaviruses represent an unusual example of a highly evolved symbiosis
      between some parasitic wasps, DNA containing particles or viruses, and
      lepidopteran larval hosts of the wasp. The viruses can no longer replicate
      independently, as genes that encode viral structural proteins are restricted to
      the wasp genome and are not encapsidated. Interestingly, the DNA that is
      encapsidated is more similar in terms of gene identity and gene density to
      eukaryotic genomes than viral genomes. We compare and relate this unusual example
      of natural genetic engineering to the well-known system of viral lysogeny. The
      similarities in the two systems may prove useful in understanding the replication
      strategy and genomic organization of polydnaviruses and provide some insight into
      how this unusual virus system may have evolved.

PMID- 19845637
TI  - Natural genetic engineering of hepatitis C virus NS5A for immune system
      counterattack.
AB  - The Hepatitis C virus nonstructural 5A (NS5A) protein is a hydrophilic
      phosphoprotein with diverse functions. The domain assignment of NS5A had been
      refined using a systematic in silico bioinformatics approach using DOMAC, the
      protein is divided into three domains and domain III is subdivided into two
      subdomains using ProDom and SSEP servers. The fold structure for domains II and
      III were predicted using the meta-server 3D-Jury. Scanning motif databases
      (SMART, BLOCKS, and PROSITE) gave new motifs. Two important motifs, the
      interleukins 1 and 8 interaction motifs, relating to NS5A function in inducing
      the interleukin 8 promoter, were discovered from the BLOCKS scan. Protein-protein
      interaction motifs were predicted as hot loops and disordered regions,
      corresponding to binding regions with the ds-protein kinase R, viral polymerase,
      and Src homology 3 signaling proteins binding motif. Other hot loops were
      predicted in the V3 region and in the single-stranded DNA-binding protein motif.
      The different mechanisms by which the NS5A protein leads to immune system
      signaling dysfunction points to the natural genetic engineering of this protein.

PMID- 19845636
TI  - Friendly viruses: the special relationship between endogenous retroviruses and
      their host.
AB  - Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and
      have coevolved with their hosts for millions of years. Some ERVs play a critical
      role in placental development, contribute to genome plasticity, and protect the
      host against infection of related pathogenic and exogenous retroviruses, thus
      some ERVs have been positively selected and maintained in the host genome. The
      sheep genome contains 27 endogenous retroviruses (enJSRVs) related to the
      pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a
      transmissible lung cancer in sheep. enJSRVs are able to protect their host
      against JSRV infection by blocking different steps of the viral replication
      cycle. In addition, enJSRVs are absolutely required for sheep placental
      development. Thus, enJSRVs-JSRV provides a unique and interesting model to study
      the symbiotic relationship and interplay between host ERVs and evolution. This
      review will provide some examples of the biological functions of ERVs. In
      particular, the role of ERVs in reproductive biology and in protecting the host
      against pathogenic retrovirus infections will be emphasized using enJSRVs/JSRV
      and the sheep as a model.

PMID- 19845638
TI  - The fragmented gene.
AB  - While once almost synonymous, there is an increasing gap between the expanding
      definition of what constitutes a gene and the conservative and narrowly defined
      terms code or coding, which for a long time, almost exclusively constituted the
      open reading frame. Much confusion results from this disparity, especially in
      light of the plethora of noncoding RNAs (more correctly termed "non-protein
      coding RNAs") that usually are encoded and transcribed by their own genes. A
      simple solution would be to adopt Ed Trifonov's less constrained definition of a
      code as any sequence pattern that can have a biological function. Such
      consideration favors not only a more complex view of the gene as an entity
      composed of many more or less conserved subgenic modules, but also a concept of
      modular evolution of genes and entire genomes.

PMID- 19845639
TI  - The source of self: genetic parasites and the origin of adaptive immunity.
AB  - Stable colonization of the host by viruses (genetic parasites) can alter the
      systems of host identity and provide immunity against related viruses. To attain
      the needed stability, some viruses of prokaryotes (P1 phage) use a strategy
      called an addiction module. The linked protective and destructive gene functions
      of an addiction module insures both virus persistence but will also destroy cells
      that interrupt this module and thereby prevent infection by competitors.
      Previously, I have generalized this concept to also include persistent and lytic
      states of virus infection, which can be considered as a virus addiction module.
      Such states often involve defective viruses. In this report, I examine the origin
      of the adaptive immune system from the perspective of a virus addiction module.
      The likely role of both endogenous and exogenous retroviruses, DNA viruses, and
      their defective elements is considered in the origin of all the basal components
      of adaptive immunity (T-cell receptor, RAG-mediated gene rearrangement, clonal
      lymphocyte proliferation, antigen surface presentation, apoptosis, and education
      of immune cells). It is concluded that colonization by viruses and their
      defectives provides a more coherent explanation for the origin of adaptive
      immunity.

PMID- 19845640
TI  - Cellular genes derived from Gypsy/Ty3 retrotransposons in mammalian genomes.
AB  - Gypsy/Ty3 retrotransposons, a group of long terminal repeat retrotransposons
      related to vertebrate retroviruses, are found in the genome of many fungi,
      plants, and animals. Although multiple families of such retroelements are present
      in fish, active Gypsy/Ty3 retrotransposons have all been eliminated from the
      lineage leading to mammals at least 180 million years ago. However, over 50
      cellular genes related to Gypsy/Ty3 retrotransposons have been identified in
      mammalian genomes, indicating recurrent "molecular domestication" of these
      elements by their host during evolution. Most retrotransposon-derived proteins
      are conserved in divergent mammalian species and show sequence similarity to Gag
      proteins, major structural proteins for retroelement particle formation. Among
      the proposed and demonstrated biological functions for gag-derived genes,
      placenta formation in the mouse requires two gag-derived genes from the same
      family. Some forms of epigenetic regulation of gag-related genes might derive
      from host genome defense mechanisms that repelled retrotransposon ancestors.
      Together, such observations support a major role for transposable elements as a
      source of new coding sequences allowing important genetic innovations during
      evolution.

PMID- 19845641
TI  - Noncoding RNAs: persistent viral agents as modular tools for cellular needs.
AB  - It appears that all the detailed steps of evolution stored in DNA that are read,
      transcribed, and translated in every developmental and growth process of each
      individual cell depend on RNA-mediated processes, in most cases interconnected
      with other RNAs and their associated protein complexes and functions in a strict
      hierarchy of temporal and spatial steps. Life could not function without the key
      agents of DNA replication, namely mRNA, tRNA, and rRNA. Not only rRNA, but also
      tRNA and the processing of the primary transcript into the pre-mRNA and the
      mature mRNA are clearly descended from retro-"elements" with obvious retroviral
      ancestry. They seem to be remnants of viral infection events that did not kill
      their host but transferred phenotypic competences to their host and changed both
      the genetic identity of the host organism and the identity of the former
      infectious viral swarms. In this respect, noncoding RNAs may represent a great
      variety of modular tools for cellular needs that are derived from persistent
      nonlytic viral settlers.

PMID- 19845643
TI  - Epigenetic regulation of Mammalian genomes by transposable elements.
AB  - Transposable element (TE) sequences make up a substantial fraction of mammalian
      genomes and exert a variety of regulatory influences on mammalian genes. We
      explore the contributions of TEs to the epigenetic mechanisms that regulate
      mammalian genomes, emphasizing nucleosome positioning and epigenetic histone
      modifications. A link between TEs and epigenetics rests on the fact that
      underlying genetic sequences partially mediate the nature and identity of
      epigenetic modifications. Here, we review the studies that have uncovered histone
      modifications that are targeted to mammalian TE sequences and propose a series of
      hypotheses regarding the potential epigenetic regulatory effects of mammalian
      TEs. We propose that mammalian TE sequences have specific nucleosome binding
      properties with regulatory implications for nearby genes, are involved in the
      phasing of nucleosomes, and recruit epigenetic modifications to function as
      enhancers; that epigenetic modifications at TE sequences affect the regulation of
      nearby genes; and that TEs serve as epigenetic boundary elements. It is hoped
      that these proposed scenarios may help to serve as a roadmap for future
      investigations into the epigenetic regulatory effects of mammalian TEs.

PMID- 19845642
TI  - APOBEC3 proteins inhibit LINE-1 retrotransposition in the absence of ORF1p
      binding.
AB  - Members of the apolipoprotein B mRNA editing complex polypeptide 1-like (APOBEC)
      family of enzymes exhibit inhibitory activity against a variety of exogenous and
      endogenous retroviruses including retrotransposons, such as long interspersed
      element 1 (LINE-1). Indeed, human APOBEC3A, APOBEC3B, and APOBEC3F inhibit
      retrotransposition of human LINE-1, mouse IAP and MusD retrotransposons. In our
      study, we examined whether the inhibitory effect of APOBEC3 proteins correlates
      with APOBEC3 ability to bind the LINE-1 ORF1 protein. We examined the
      interactions between the LINE-1 ORF1 protein and the most potent LINE-1
      retrotransposon inhibitors, human APOBEC3A and APOBEC3B, by immunofluorescence
      and immunoprecipitation. Although human APOBEC3A shows the highest inhibitory
      potency against LINE-1 retrotransposon, no direct interactions were identified
      either by immunofluorescence or by co-immunoprecipitation. APOBEC3B binds to LINE
      1 ORF1 protein, yet no co-localization was detected. We concluded that APOBEC3
      proteins interfere indirectly with the LINE-1 retrotransposition pathway,
      probably through interference with RNA targeting.

PMID- 19845644
TI  - Are there epigenetic controls in Trypanosoma cruzi?
AB  - RNA interference (RNAi) is defined as the mechanism through which double-stranded
      RNA (dsRNA) triggers degradation of homologous transcripts. Besides providing an
      invaluable tool to downregulate gene expression in a variety of organisms, it is
      now evident that RNAi acts beyond the cytoplasm and is involved in a variety of
      gene-silencing phenomena in the nucleus. In the present work we review the
      current status of the knowledge about RNAi in protozoan parasites that belong to
      the Trypanosoma genus and have medical relevance. While RNAi was first discovered
      in Trypanosoma brucei, it became evident that other members of the same genus of
      organisms, namely Trypanosoma cruzi, does not possess RNAi, probably due to the
      lack of Ago protein analogs in their genomes. We will discuss the genome
      organization of Trypanosoma cruzi and propose that the absence of both RNAi and
      gene promoters is symptomatic of alternative epigenetic controls in this parasite
      orchestrated by parasite-host interactions. Whereas in Trypanosoma brucei, RNAi
      and other epigenetic controls dictate alternative transcriptional programs
      critical for virulence.

PMID- 19845645
TI  - Conceptual and methodological biases in network models.
AB  - Many natural and biological phenomena can be depicted as networks. Theoretical
      and empirical analyses of networks have become prevalent. I discuss theoretical
      biases involved in the delineation of biological networks. The network
      perspective is shown to dissolve the distinction between regulatory architecture
      and regulatory state, consistent with the theoretical impossibility of
      distinguishing a priori between "program" and "data." The evolutionary
      significance of the dynamics of trans-generational and interorganism regulatory
      networks is explored and implications are presented for understanding the
      evolution of the biological categories development-heredity, plasticity
      evolvability, and epigenetic-genetic.

PMID- 19845646
TI  - No genetics without epigenetics? No biology without systems biology?
AB  - In this article, we propose to reflect on the meaning of complexity in relation
      to current biology, and in particular, in relation to current systems biological
      developments by considering them as confronting biology with the idea of a
      complex part-whole determination of living systems, that is contextual as well as
      stratified. We attempt to trace as clearly as possible the abstract core of the
      idea of parts and wholes that is at stake in this contextual determination. In
      doing so, we have found inspiration in Kant's view on living systems. We argue
      that Kant's transcendental viewpoint can be relevantly actualized and
      extrapolated as a relational account of living systems, and will explore its
      ramifications starting from a multilevel view of living systems.

PMID- 19845649
TI  - Review of non-convulsive status epilepticus and an illustrative case history
      manifesting as delirium.
AB  - Non-convulsive status epilepticus can result in significant morbidity and
      mortality. The condition can be difficult to recognise, and can mimic delirium
      due to other underlying pathologies. There are several clinical subtypes,
      although these can be difficult to distinguish by their clinical features alone.
      Electroencephalogram is the key diagnostic tool to making the diagnosis, but this
      investigation is a limited resource in many institutions. In this review, we
      present a case of non-convulsive status epilepticus, manifesting as delirium, and
      then proceed to a literature review on this important diagnosis.

PMID- 19845650
TI  - What makes a community age-friendly: A review of international literature.
AB  - This paper undertakes a comprehensive review of the growing international
      literature on age-friendly communities. It examines a range of approaches and
      identifies the key attributes associated with creating a sustainable environment
      for seniors. The authors critically evaluate emerging policy trends and models
      and suggest directions for future research attention. The discussion provides
      important information and insights for the development of ageing policy and
      planning in Australia.

PMID- 19845651
TI  - Management and organisational barriers in the acquisition of computer usage
      skills by mature age workers.
AB  - AIM: To investigate workplace cultures in the acquisition of computer usage
      skills by mature age workers. METHODS: Data were gathered through focus groups
      conducted at job network centres in the Greater Brisbane metropolitan region.
      Participants who took part were a mixture of workers and job-seekers. RESULTS:
      The results suggest that mature age workers can be exposed to inappropriate
      computer training practices and age-insensitive attitudes towards those with low
      base computer skills. CONCLUSIONS: There is a need for managers to be observant
      of ageist attitudes in the work place and to develop age-sensitive strategies to
      help mature age workers learn computer usage skills. Mature age workers also need
      to develop skills in ways which are practical and meaningful to their work.

PMID- 19845652
TI  - Physical activity of older Australians measured by pedometry.
AB  - AIM: To established population norms for pedometer determined step counts in
      older Australians. METHODS: A representative sample of 684 participants over the
      age of 55 years wore a pedometer for a week in Newcastle, Australia. RESULTS:
      Response rate was 32%. Median daily step count was 8605 in those aged 55-59 years
      declining to 3778 in those over 80 years old. The proportion who reached 8000
      steps per day was 62% in those 55-59 years and 12% in those over 80 years. Daily
      step counts were highest on Thursdays and Fridays and least on Sundays. Weekend
      days had on average 620 less steps than weekdays. After adjusting for age, there
      was a negative association of step count with body mass index >30, and with a
      history of arthritis but no significant association with other demographic
      variables. CONCLUSION: Pedometry is feasible in an elderly sample, and research
      involving pedometers must take days of the week into account.

PMID- 19845653
TI  - Medical masters: A pilot study of adaptive ageing in physicians.
AB  - AIM: To describe models of career and lifestyle options for ageing doctors that
      suggest adaptability to ageing and retirement. METHOD: Doctors aged 60 or older
      from Australia, Canada and the United States (n= 25) deemed to be ageing well by
      peers were administered a semistructured interview to obtain demographic and
      qualitative data regarding lifestyle, attitudes to ageing and retirement.
      RESULTS: Emergent themes included: (i) insights into the physical and
      psychological vicissitudes of ageing and the effects of such on practice; (ii)
      the need for adaptations in working hours and choice of work; (iii) the
      importance of long-term retirement planning; (iv) the usefulness of a
      transitional phase to ease into retirement; and (v) the need to cultivate a
      variety of medical and non-medical pursuits and relationships early in one's
      career. CONCLUSION: These insights might encourage doctors to engage in long-term
      occupational, familial, social and financial planning and provide potential
      models of adaptive ageing in doctors for further study.

PMID- 19845654
TI  - Four-item fall risk screening tool for subacute and residential aged care: The
      first step in fall prevention.
AB  - AIM: To report the reliability, accuracy and compliance of a brief fall risk
      screening tool in subacute and residential aged care. METHOD: A 9-item tool,
      developed by expert and literature review, was administered to 291 persons
      admitted to subacute and residential aged care at Peninsula Health (PH) Victoria,
      Australia. Items were analysed for their ability to predict falls and the four
      strongest incorporated into a screening tool. Reliability was assessed on six
      nurses. RESULTS: Most predictive items were recent falls (0.82), psychological
      status (0.55), medications (0.46) and cognition (0.41) chi(2) (4, n= 291) =
      89.89, P < 0.0001. The final 4-item tool (PH-FRAT) provides 80% accuracy
      (sensitivity(ER) 70.2%, specificity(ER) 68.8%) and high reliability (ICC = 0.79).
      The PH-FRAT is now used in 50 local subacute and residential facilities.
      CONCLUSION: The 4-item PH-FRAT is a popular, moderately predictive, reliable and
      brief method of screening fall risk in subacute and residential aged care.

PMID- 19845655
TI  - Future research on dementia relating to culturally and linguistically diverse
      communities.
AB  - About one in five older Australians were born overseas. However, there has been
      very little information published in Australia or internationally about dementia
      in persons from culturally and linguistically diverse (CALD) backgrounds. This
      limits our ability to plan for and provide evidence-based medical care, social
      care and aged care services to persons from CALD backgrounds. This paper
      describes challenges to conducting CALD dementia research; these include
      sampling, having valid instruments and costs. Nine key research recommendations
      in the areas of epidemiology, community knowledge, carers, service delivery,
      screening and assessment, medical management, residential aged care and minority
      CALD reached by consensus by an expert group are presented. The paper closes with
      some strategies to encourage CALD research. The material presented here will
      provide guidance for future research endeavours.

PMID- 19845656
TI  - Recruiting older adults to health research studies: A systematic review.
AB  - AIM: To provide a systematic review of papers comparing the effectiveness of
      different strategies to recruit older adults (aged 50 years and over) to
      participate in health research studies, to guide successful recruitment in future
      research. METHODS: Four major databases were searched for papers published
      between 1995 and 2008 with: target group aged 50 years or over; participants
      allocated to receive one of two or more recruitment strategies; and an outcome
      measure of response rate or enrolment in study. RESULTS: Twelve papers were
      included in the review. CONCLUSION: For postal questionnaires, recruitment
      strategies used with older adults had comparable outcomes to those used to
      recruit from the general population. For other types of studies, strategies
      involving face-to-face contact may be more effective than indirect methods, but
      this needs to be balanced against feasibility. Overall, little evidence on the
      topic exists and more rigorous investigation is necessary.

PMID- 19845657
TI  - Comprehensive geriatric assessment for the private hospital inpatient.

PMID- 19845658
TI  - Australian and New Zealand Society for Geriatric Medicine position statement no.
      14 guidelines for the management of older persons presenting to emergency
      departments 2008.

PMID- 19845659
TI  - Australian and New Zealand Society for Geriatric Medicine position statement no.
      15 discharge planning.

PMID- 19845664
TI  - FGFR3 and PIK3CA mutations in stucco keratosis and dermatosis papulosa nigra.
AB  - BACKGROUND: Stucco keratosis (STK) and dermatosis papulosa nigra (DPN) are
      referred to as variants of seborrhoeic keratosis. However, the genetic
      alterations involved in the pathogenesis of these benign tumours are unknown.
      OBJECTIVES: Because FGFR3 and PIK3CA mutations have been reported to be involved
      in the pathogenesis of seborrhoeic keratosis, we analysed whether these mutations
      are also present in STK and DPN. Methods A SNaPshot multiplex assay was used for
      analysis of 11 previously described FGFR3 hotspot mutations. PIK3CA mutations
      were analysed by a SNaPshot assay covering five PIK3CA hotspot mutations.
      RESULTS: Five STK and two DPN samples were analysed. Three of five STK samples
      revealed a PIK3CA mutation (E542K, E545K), but no FGFR3 mutation was found. In
      contrast, both DPN samples harboured an FGFR3 mutation (R248C, S249C) but no
      PIK3CA mutation. Control tissues available for three samples did not show PIK3CA
      or FGFR3 mutations, excluding germline mutations and indicating a strong genotype
      phenotype correlation between the mutation and the lesion. CONCLUSIONS: These
      results indicate that FGFR3 and PIK3CA mutations are involved in the pathogenesis
      of STK and DPN. The molecular genetic findings furthermore support the concept
      that both skin lesions are specific variants of seborrhoeic keratosis, sharing a
      common genetic background.

PMID- 19845665
TI  - Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl
      antibody.
AB  - BACKGROUND: To date, no series has analysed long-term outcome in patients with
      polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody. OBJECTIVES: The
      aims of the present study were: (i) to assess clinical features and long-term
      outcome, including organ complications, functional course and mortality rate, in
      patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate
      prevalence, characteristics and long-term outcome of interstitial lung disease
      (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody. METHODS: The
      medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl
      antibody were reviewed. RESULTS: Two patients (10%) achieved remission of PM/DM,
      whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short
      term recurrences (during tapering of therapy) occurred in nine patients and long
      term recurrences (after discontinuation of therapy) in three patients. Moreover,
      patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as
      follows: oesophageal involvement (n = 4) requiring enteral feeding in three
      cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two
      cases; three other patients had cancer. Interestingly, patients with PM/DM with
      anti-PM-Scl antibody often presented symptoms that are usually found in
      antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2;
      10%), Raynaud's phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and
      ILD (n = 12; 60%). In our cohort, the associated ILD often required combined
      therapy of steroids and immunosuppressive agents. CONCLUSIONS: Our series
      suggests that the presence of anti-PM-Scl antibody is not a good prognostic
      factor in patients with PM/DM, as there appears to be an association with lung
      and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with
      malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive
      patients with PM/DM often exhibit 'mechanic's hands', Raynaud's phenomenon and
      joint involvement. Our latter findings raise the possibility that the
      immunogenetic background influences the autoantibody status of these patients;
      HLA-DR3 has, in fact, been found in association with antisynthetase syndrome
      antibodies and with anti-PM-Scl antibodies.

PMID- 19845666
TI  - Clothing reduces the sun protection factor of sunscreens.
AB  - BACKGROUND: Individuals are recommended to wait for 20 min following sunscreen
      application before dressing. However, this is probably seldom done in daily life,
      and therefore we investigated how dressing earlier than 20 min after application
      affected the sun protection factor (SPF). OBJECTIVES: To determine the SPF of a
      sunscreen applied at different amounts at 4, 8 and 20 min before dressing.
      METHODS: An organic sunscreen was used on the backs of 22 healthy volunteers.
      Before SPF testing, participants wore a cotton T-shirt for 60 min after the test
      areas had been uncovered for 4, 8 or 20 min after sunscreen application. The SPF
      was also tested on unclothed skin. RESULTS: The median SPF was 11.7 (2 mg cm(
      2)), 5.7 (1 mg cm(-2)) and 3.3 (0.5 mg cm(-2)) for unclothed skin, and 8.1 (2 mg
      cm(-2)), 4.8 (1 mg cm(-2)) and 2.2 (0.5 mg cm(-2)) following an interval of 8 min
      before dressing. The SPF was similar for time intervals of 20 and 8 min when the
      amount was 1 mg cm(-2) (P = 0.48) and 2 mg cm(-2) (P = 0.56). For 0.5 mg cm(-2)
      there was no difference between skin clothed after 20 min and unclothed skin (P =
      0.19), nor between skin clothed after 4 min and after 8 min (P = 0.28).
      CONCLUSIONS: When sunscreens are applied at amounts of 1 and 2 mg cm(-2) the time
      between sunscreen application and dressing can be as little as 8 min. When less
      sunscreen is used the SPF is insensitive to the length of time between
      application and dressing.

PMID- 19845667
TI  - Reduction in the appearance of facial hyperpigmentation after use of moisturizers
      with a combination of topical niacinamide and N-acetyl glucosamine: results of a
      randomized, double-blind, vehicle-controlled trial.
AB  - BACKGROUND: Topical niacinamide and N-acetyl glucosamine (NAG) each individually
      inhibit epidermal pigmentation in cell culture. In small clinical studies,
      niacinamide-containing and NAG-containing formulations reduced the appearance of
      hyperpigmentation. OBJECTIVES: To assess the effect of a combination of
      niacinamide and NAG in a topical moisturizing formulation on irregular facial
      pigmentation, including specific detection of changes in colour features
      associated with melanin. METHODS: This was a 10-week, double-blind, vehicle
      controlled, full-face, parallel-group clinical study conducted in women aged 40
      60 years. After a 2-week washout period, subjects used a daily regimen of either
      a morning sun protection factor (SPF) 15 sunscreen moisturizing lotion and
      evening moisturizing cream each containing 4% niacinamide + 2% NAG (test
      formulation; n = 101) or the SPF 15 lotion and cream vehicles (vehicle control; n
      = 101). Product-induced changes in apparent pigmentation were assessed by
      capturing digital photographic images of the women after 0, 4, 6 and 8 weeks of
      product use and evaluating the images by algorithm-based computer image analysis
      for coloured spot area fraction, by expert visual grading, and by chromophore
      specific image analysis based on noncontact SIAscopy for melanin spot area
      fraction and melanin chromophore evenness. RESULTS: By all four measures, the
      niacinamide + NAG formulation regimen was significantly (P < 0.05) more effective
      than the vehicle control formulation regimen in reducing the detectable area of
      facial spots and the appearance of pigmentation. CONCLUSIONS: A formulation
      containing the combination of niacinamide + NAG reduced the appearance of
      irregular pigmentation including hypermelaninization, providing an effect beyond
      that achieved with SPF 15 sunscreen.

PMID- 19845668
TI  - FOXE1 is a target for aberrant methylation in cutaneous squamous cell carcinoma.
AB  - BACKGROUND: Several cancer-related genes are silenced by promoter
      hypermethylation in skin cancers. However, to date the somatic epigenetic events
      that occur in cutaneous squamous cell carcinoma (SCC) tumorigenesis have not been
      well defined. OBJECTIVES: To examine epigenetic abnormalities of FOXE1, a gene
      located on chromosome 9q22, a region frequently lost in SCC. METHODS: We
      investigated the methylation status of FOXE1 in 60 cases of cutaneous SCC by
      methylation-specific polymerase chain reaction, and comparatively examined mRNA
      and protein expression by real-time polymerase chain reaction and Western blot,
      respectively. RESULTS: We found a higher frequency of FOXE1 promoter
      hypermethylation in SCCs (55%), as compared with the adjacent uninvolved skin
      (12%) and blood control samples (9.5%). FOXE1 methylation was frequently seen in
      association with a complete absence of or downregulated gene expression.
      Treatment with the demethylating agent 5-Aza-2'-deoxycytidine resulted in
      profound reactivation of FOXE1 expression. CONCLUSIONS: These results indicate
      that FOXE1 is a crucial player in development of cutaneous SCC.

PMID- 19845669
TI  - Desensitization of endothelial P2Y1 receptors by PKC-dependent mechanisms in
      pressurized rat small mesenteric arteries.
AB  - BACKGROUND AND PURPOSE: Extracellular nucleotides play a crucial role in the
      regulation of vascular tone and blood flow. Stimulation of endothelial cell P2Y1
      receptors evokes concentration-dependent full dilatation of resistance arteries.
      However, this GPCR can desensitize upon prolonged exposure to the agonist. Our
      aim was to determine the extent and nature of P2Y1 desensitization in isolated
      and pressurized rat small mesenteric arteries. EXPERIMENTAL APPROACH: The non
      hydrolyzable selective P2Y1 agonist ADPbetaS (3 microM) was perfused through the
      lumen of arteries pressurized to 70 mmHg. Changes in arterial diameter and
      endothelial cell [Ca(2+)](i) were obtained in the presence and absence of
      inhibitors of protein kinase C (PKC). KEY RESULTS: ADPbetaS evoked rapid
      dilatation to the maximum arterial diameter but faded over time to a much-reduced
      plateau closer to 35% dilatation. This appeared to be due to desensitization of
      the P2Y1 receptor, as subsequent endothelium-dependent dilatation to
      acetylcholine (1 microM) remained unaffected. Luminal treatment with the PKC
      inhibitors BIS-I (1 microM) or BIS-VIII (1 microM) tended to augment
      concentration-dependent dilatation to ADPbetaS (0.1-3 microM) and prevented
      desensitization. Another PKC inhibitor, Go 6976 (1 microM), was less effective in
      preventing desensitization. Measurements of endothelial cell [Ca(2+)](i) in
      pressurized arteries confirmed the P2Y1 receptor but not M(3) muscarinic receptor
      desensitization. CONCLUSIONS AND IMPLICATIONS: These data demonstrate for the
      first time the involvement of PKC in the desensitization of endothelial P2Y1
      receptors in pressurized rat mesenteric arteries, which may have important
      implications in the control of blood flow by circulating nucleotides.

PMID- 19845671
TI  - Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive
      agents.
AB  - BACKGROUND AND PURPOSE: The transient receptor potential ankyrin receptor 1
      (TRPA1) is a cation channel, co-expressed with the pro-tussive transient receptor
      potential vanilloid type 1 (TRPV1) channel in primary sensory neurons. TRPA1 is
      activated by a series of irritant exogenous and endogenous alpha,beta-unsaturated
      aldehydes which seem to play a role in airway diseases. We investigated whether
      TRPA1 agonists provoke cough in guinea pigs and whether TRPA1 antagonists inhibit
      this response. EXPERIMENTAL APPROACH: Animals were placed in a Perspex box, and
      cough sounds were recorded and counted by observers unaware of the treatment
      used. KEY RESULTS: Inhalation of two selective TRPA1 agonists, allyl
      isothiocyanate and cinnamaldehyde, dose-dependently caused cough in control
      guinea pigs, but not in those with airway sensory nerves desensitized by
      capsaicin. Coughs elicited by TRPA1 agonists were reduced by non-selective
      (camphor and gentamicin) and selective (HC-030031) TRPA1 antagonists, whereas
      they were unaffected by the TRPV1 antagonist, capsazepine. Acrolein and
      crotonaldehyde, two alpha,beta-unsaturated aldehydes recently identified as TRPA1
      stimulants and contained in cigarette smoke, air pollution or produced
      endogenously by oxidative stress, caused a remarkable tussive effect, a response
      that was selectively inhibited by HC-030031. Part of the cough response induced
      by cigarette smoke inhalation was inhibited by HC-030031, suggesting the
      involvement of TRPA1. CONCLUSIONS AND IMPLICATIONS: A novel pro-tussive pathway
      involves the TRPA1 channel, expressed by capsaicin-sensitive airway sensory
      nerves and is activated by a series of exogenous (cigarette smoke) and endogenous
      irritants. These results suggest TRPA1 may be a novel target for anti-tussive
      medicines.

PMID- 19845670
TI  - Facilitation of central imidazoline I(1)-site/extracellular signal-regulated
      kinase/p38 mitogen-activated protein kinase signalling mediates the hypotensive
      effect of ethanol in rats with acute renal failure.
AB  - BACKGROUND AND PURPOSE: This study investigated the role of central sympathetic
      activity and related mitogen-activated protein kinase (MAPK) signalling in the
      cardiovascular effects of ethanol in a model of acute renal failure (ARF).
      EXPERIMENTAL APPROACH: The effects of pharmacological interventions that inhibit
      peripheral or central sympathetic activity or MAPK on the cardiovascular actions
      of ethanol in rats with ARF induced by glycerol were evaluated. KEY RESULTS:
      Glycerol (50%, 10 mL.kg(-1), i.m.) caused progressive increases and decreases in
      blood pressure (BP) and heart rate (HR) respectively. Subsequent i.v. ethanol
      (0.25 or 1 g.kg(-1)) elicited dose-related changes in BP (decreases) and HR
      (increases). These effects were replicated after intracisternal (i.c.)
      administration of ethanol. Blockade of nicotinic cholinoceptors (nAChR,
      hexamethonium, 20 mg.kg(-1)) or alpha(1)-adrenoceptors (prazosin, 1 mg.kg(-1))
      attenuated cardiovascular effects of ethanol. Ethanol hypotension was also
      attenuated after the centrally acting sympatholytic drug moxonidine (selective
      I(1)-site agonist, 100 microg.kg(-1) i.v.), but not guanabenz (selective alpha(2)
      receptor agonist, 30 microg.kg(-1), i.v.), suggesting involvement of central
      circuits of I(1) sites in ethanol-evoked hypotension. Selective blockade I(1)
      sites (efaroxan) but not alpha(2) (yohimbine) adrenoceptors abolished the
      hypotensive response to ethanol. Intracisternal administration of PD98059 or
      SB203580, inhibitors of extracellular signal-regulated kinase (ERK 1/2) and p38
      MAPK, respectively, reduced the hypotensive action of moxonidine or ethanol. When
      used simultaneously, the two MAPK inhibitors produced additive attenuation of
      ethanol hypotension. CONCLUSIONS AND IMPLICATIONS: Sympathoinhibitory pathways of
      central I(1)-sites and downstream ERK/p38 MAPK signalling were involved in the
      hypotensive action of ethanol in ARF.

PMID- 19845672
TI  - Subtype-selective targeting of voltage-gated sodium channels.
AB  - Voltage-gated sodium channels are key to the initiation and propagation of action
      potentials in electrically excitable cells. Molecular characterization has shown
      there to be nine functional members of the family, with a high degree of sequence
      homology between the channels. This homology translates into similar biophysical
      and pharmacological properties. Confidence in some of the channels as drug
      targets has been boosted by the discovery of human mutations in the genes
      encoding a number of them, which give rise to clinical conditions commensurate
      with the changes predicted from the altered channel biophysics. As a result, they
      have received much attention for their therapeutic potential. Sodium channels
      represent well-precedented drug targets as antidysrhythmics, anticonvulsants and
      local anaesthetics provide good clinical efficacy, driven through pharmacology at
      these channels. However, electrophysiological characterization of clinically
      useful compounds in recombinant expression systems shows them to be weak, with
      poor selectivity between channel types. This has led to the search for subtype
      selective modulators, which offer the promise of treatments with improved
      clinical efficacy and better toleration. Despite developments in high-throughput
      electrophysiology platforms, this has proven very challenging. Structural biology
      is beginning to offer us a greater understanding of the three-dimensional
      structure of voltage-gated ion channels, bringing with it the opportunity to do
      real structure-based drug design in the future. This discipline is still in its
      infancy, but developments with the expression and purification of prokaryotic
      sodium channels offer the promise of structure-based drug design in the not too
      distant future.

PMID- 19845673
TI  - Effects of 7,8-dihydro-8-oxo-deoxyguanosine on antigen challenge in ovalbumin
      sensitized mice may be mediated by suppression of Rac.
AB  - BACKGROUND AND PURPOSE: Earlier we reported that 7,8-dihydro-8-oxo-deoxyguanosine
      (8-oxo-dG), an oxidatively modified guanine nucleoside, exerted anti-inflammatory
      activity through inactivation of the GTP binding protein, Rac. In the present
      study, the effects of 8-oxo-dG were investigated on responses to antigen
      challenge in sensitized mice, as Rac is also involved at several steps of the
      immune process including antigen-induced release of mediators from mast cells.
      EXPERIMENTAL APPROACH: Mice were sensitized and challenged with ovalbumin without
      or with oral administration of 8-oxo-dG during the challenge. Effects of 8-oxo-dG
      were assessed by measuring lung function, cells and cytokines in broncho-alveolar
      lavage fluid (BALF) and serum levels of antigen-specific IgE. Rac activity in
      BALF cells was also measured. KEY RESULTS: 8-oxo-dG inhibited the increased
      airway resistance and decreased lung compliance of sensitized and challenged mice
      to the levels of non-sensitized control mice and lowered the increased leukocytes
      particularly, eosinophils, in BALF. Furthermore, 8-oxo-dG suppressed allergy
      associated immune responses, such as raised anti- ovalbumin IgE antibody in
      serum, increased expression of CD40 and CD40 ligand in lung, increased
      interleukin-4, -5, -13, interferon-gamma and tumour necrosis factor-alpha in BALF
      and mRNA levels of these cytokines in BALF cells, dose-dependently. The
      corresponding purine, 8-oxo-guanine, showed no effects in the same experiments.
      Finally, 8-oxo-dG, but not 8-oxo-guanine, inhibited the increased Rac activity in
      sensitized and challenged mice. CONCLUSION AND IMPLICATIONS: 8-Oxo-dG had anti
      allergic actions that might be mediated by Rac inactivation. This compound merits
      further evaluation of its therapeutic potential in allergic asthma.

PMID- 19845674
TI  - Effect of the CB(1) receptor antagonists rimonabant and AM251 on the firing rate
      of dorsal raphe nucleus neurons in rat brain slices.
AB  - BACKGROUND AND PURPOSE: Previous studies have suggested a regulation of 5
      hydroxytryptamine (5-HT) neurons by the endocannabinoid system. The aim of our
      work was to examine the effect of two CB(1) receptor antagonists, SR141716A
      (rimonabant, Sanofi-Synthelabo Recherche, Montpellier, France) and N-(piperidin-1
      yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      (AM251, Tocris Cookson, Bristol, UK), on the firing rate of dorsal raphe nucleus
      (DRN) neurons. EXPERIMENTAL APPROACH: Single-unit extracellular recordings were
      performed to study the effect of CB(1) receptor antagonists in slices of the DRN
      from rat brain. KEY RESULTS: Rimonabant (1 microM) and AM251 (1 microM) decreased
      the firing rate of about 50% of all the recorded DRN 5-HT cells. The
      GABA(A)receptor antagonist picrotoxin (20 microM) (Sigma) prevented and also
      reversed the inhibitory effect of rimonabant (1 microM) and AM251 (1 microM),
      suggesting that CB(1) receptors regulate 5-HT neurons through the GABAergic
      system. However, the CB(1)/CB(2) receptor agonist R-(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)-methyl]pyrrolol[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)
      methanone mesylate salt (10 microM) (WIN55212-2, Sigma, St. Louis, MO, USA)
      failed to change the firing activity of non-5-HT (presumably GABAergic) neurons
      in the DRN. The endocannabinoid N-(2-hydroxyethyl)-5Z,8Z,11Z,14Z
      eicosatetraenamide (anandamide, Tocris Cookson) (10 microM) also inhibited the
      firing activity of a number of 5-HT neurons, but this inhibition was not blocked
      by rimonabant (1 microM) or AM251 (1 microM), and the stable analogue R-(+) N-(2
      hydroxy-1methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (methanandamide, Tocris
      Cookson) (10 microM) did not mimic this effect. The selective CB(1) receptor
      agonist arachidonoyl-2-chloroethylamide (ACEA) (1 microM) only slightly increased
      the firing rate of DRN 5-HT cells. CONCLUSIONS AND IMPLICATIONS: These results
      suggest a tonic/constitutive regulation of DRN 5-HT neurons by the
      endocannabinoid system, which may occur through a CB(1) receptor-mediated
      inhibition of the GABAergic system. The inhibitory effect of anandamide may be
      mediated through a CB(1) receptor-independent mechanism.

PMID- 19845675
TI  - Role of channel activation in cognitive enhancement mediated by alpha7 nicotinic
      acetylcholine receptors.
AB  - BACKGROUND AND PURPOSE: Several agonists of the alpha7 nicotinic acetylcholine
      receptor (nAChR) have been developed for treatment of cognitive deficits.
      However, agonist efficacy in vivo is difficult to reconcile with rapid alpha7
      nAChR desensitization in vitro; and furthermore, the correlation between in vitro
      receptor efficacy and in vivo behavioural efficacy is not well delineated. The
      possibility that agonists of this receptor actually function in vivo as
      inhibitors via desensitization has not been finally resolved. EXPERIMENTAL
      APPROACH: Two structurally related alpha7 nAChR agonists were characterized and
      used to assess the degree of efficacy required in a behavioural paradigm. KEY
      RESULTS: NS6784 activated human and rat alpha7 nAChR with EC(50)s of 0.72 and
      0.88 microM, and apparent efficacies of 77 and 97% respectively. NS6740, in
      contrast, displayed little efficacy at alpha7 nAChR (<2% in oocytes, < or =8% in
      GH4C1 cells), although its agonist-like properties were revealed by adding a
      positive allosteric modulator of alpha7 nAChRs or using the slowly desensitizing
      alpha7V274T receptor. In mouse inhibitory avoidance (IA) memory retention, NS6784
      enhanced performance as did the 60% partial agonist A-582941. In contrast, NS6740
      did not enhance performance, but blocked effects of A-582941. CONCLUSIONS AND
      IMPLICATIONS: Collectively, these findings suggest that a degree of alpha7 nAChR
      agonist efficacy is required for behavioural effects in the IA paradigm, and that
      such behavioural efficacy is not due to alpha7 nAChR desensitization. Also, a
      partial agonist of very low efficacy for this receptor could be used as an
      inhibitor, in the absence of alpha7 nAChR antagonists with favourable CNS
      penetration.

PMID- 19845676
TI  - Hyperlipidaemia induced by a high-cholesterol diet leads to the deterioration of
      guanosine-3',5'-cyclic monophosphate/protein kinase G-dependent cardioprotection
      in rats.
AB  - BACKGROUND AND PURPOSE: Hyperlipidaemia interferes with cardioprotective
      mechanisms, but the cause of this phenomenon is largely unknown, although
      hyperlipidaemia impairs the cardioprotective NO-cGMP system. However, it is not
      known if natriuretic peptide-cGMP-protein kinase G (PKG) signalling is affected
      by hyperlipidaemia. Therefore, we investigated the cardioprotective efficacy of
      cGMP-elevating agents in hearts from normal and hyperlipidaemic rats.
      EXPERIMENTAL APPROACH: Male Wistar rats were rendered hyperlipidaemic by feeding
      with 2% cholesterol-enriched chow for 12 weeks. Hearts isolated from normal and
      hyperlipidaemic rats were perfused (Langendorff mode) and subjected to 30 min
      occlusion of the left main coronary artery, followed by 120 min reperfusion. 8-Br
      cGMP (CG, 10 nM), B-type natriuretic peptide-32 (BNP, 10 nM), S-nitroso-N-acetyl
      penicillamine (SNAP, 1 microM) were perfused from 10 min prior to coronary
      occlusion until the 15th min of reperfusion. Infarct size (% of ischaemic risk
      zone) was determined by triphenyltetrazolium staining. KEY RESULTS: Treatment
      with CG, SNAP or BNP decreased infarct size significantly in normal hearts from
      its control value of 41.6 +/- 2.9% to 15.5 +/- 2.4%, 23.3 +/- 3.0% and 25.3 +/-
      4.6%, respectively (P < 0.05). Protection by BNP was abolished by co-perfusion of
      PKG inhibitors KT5823 (600 nM) or Rp-8pCPT-PET-cGMPs (1 microM), confirming its
      PKG dependence. In hearts from hyperlipidaemic rats, CG, SNAP or BNP failed to
      decrease infarct size. Hyperlipidaemia did not alter basal myocardial PKG
      content, but decreased its activity as assessed by phosphorylation of cardiac
      troponin I. CONCLUSIONS AND IMPLICATIONS: This is the first demonstration that
      defects in the cardioprotective cGMP-PKG system could be a critical biochemical
      anomaly in hyperlipidaemia.

PMID- 19845677
TI  - Effect of tecarfarin, a novel vitamin K epoxide reductase inhibitor, on
      coagulation in beagle dogs.
AB  - BACKGROUND AND PURPOSE: Tecarfarin (ATI-5923) is a novel vitamin K epoxide
      reductase inhibitor that is metabolized by esterase (mainly human
      carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and
      humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The
      objective of this study was to test and compare the efficacy of tecarfarin with
      that of warfarin, when administered either intravenously or once a day orally, to
      produce stable anticoagulation in beagle dogs. EXPERIMENTAL APPROACH: Effects on
      coagulation were assessed by measuring the activity levels of Factor VII and
      Factor X and thromboplastin-induced coagulation times, reported as prothrombin
      time (PT). KEY RESULTS: Continuous intravenous infusions and oral administration
      of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor
      VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine
      plasma or subcutaneous vitamin K(1) treatment reversed the anticoagulant effects
      of orally administered tecarfarin. Consistent with the inhibitory effects of
      amiodarone on CYP2C9, co-administration of amiodarone significantly increased the
      anticoagulation effect of warfarin and plasma warfarin concentrations. In
      contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin
      or tecarfarin plasma concentrations in this model. CONCLUSIONS AND IMPLICATIONS:
      Overall, the data presented herein indicate that tecarfarin, via a vitamin K
      dependent mechanism, causes changes in key parameters of haemostasis in beagle
      dogs that are consistent with effective anticoagulation. Compared to warfarin it
      has a decreased potential to interact metabolically with drugs that inhibit
      CYP450 enzymes and, therefore, may offer an improved safety profile for patients.

PMID- 19845678
TI  - Haem oxygenase-1 induction protects against tumour necrosis factor alpha
      impairment of endothelial-dependent relaxation in rat isolated pulmonary artery.
AB  - BACKGROUND AND PURPOSE: Disturbances in pulmonary vascular reactivity are
      important components of inflammatory lung disease. Haem oxygenase-1 (HO-1) is an
      important homeostatic enzyme upregulated in inflammation. Here we have
      investigated the potentially protective effect of HO-1 against cytokine-induced
      impairment in pulmonary artery relaxation. EXPERIMENTAL APPROACH: Haem oxygenase
      1 protein levels were assessed by immunofluorescence. HO activity was assessed by
      conversion of haemin to bilirubin. Rings of rat isolated pulmonary artery in
      organ baths were used to measure relaxant responses to the endothelium-dependent
      agent ACh and the endothelium-independent agent sodium nitroprusside (SNP).
      Production of nitric oxide (NO) and reactive oxygen species (ROS) was assessed by
      confocal fluorescence microscopy and fluorescent probes. KEY RESULTS: Haem
      oxygenase-1 protein expression was strongly induced in pulmonary artery after 24
      h incubation with either haemin (5 microM) or curcumin (2 microM), accompanied by
      a significant increase in HO activity. Incubation with tumour necrosis factor
      alpha (TNFalpha, 1 ng.mL(-1), 2 h) significantly decreased relaxation of arterial
      rings to ACh, without affecting responses to SNP. Induction of HO-1 by curcumin
      or haemin protected against TNFalpha-induced hyporesponsiveness to ACh. The
      competitive HO inhibitor, tin protoporphyrin (20 microM), abolished the
      protective effect of haemin. HO-1 induction prevented a TNFalpha-induced increase
      in NO generation without affecting the TNFalpha-induced increase in ROS
      generation. HO-1 induction prevented the TNFalpha-induced decrease in ACh
      stimulated NO generation. CONCLUSIONS AND IMPLICATIONS: Induction of HO-1
      protected against TNFalpha impairment of endothelium-dependent relaxation in
      pulmonary artery, by a mechanism involving a reduction in inducible NO synthase
      derived NO production.

PMID- 19845679
TI  - Inhibition of nitric oxide-activated guanylyl cyclase by calmodulin antagonists.
AB  - BACKGROUND AND PURPOSE: Nitric oxide (NO) controls numerous physiological
      processes by activation of its receptor, guanylyl cyclase (sGC), leading to the
      accumulation of 3'-5' cyclic guanosine monophosphate (cGMP). Ca(2+)-calmodulin
      (CaM) regulates both NO synthesis by NO synthase and cGMP hydrolysis by
      phosphodiesterase-1. We report that, unexpectedly, the CaM antagonists,
      calmidazolium, phenoxybenzamine and trifluoperazine, also inhibited cGMP
      accumulation in cerebellar cells evoked by an exogenous NO donor, with IC(50)
      values of 11, 80 and 180 microM respectively. Here we sought to elucidate the
      underlying mechanism(s). EXPERIMENTAL APPROACH: We used cerebellar cell
      suspensions to determine the influence of CaM antagonists on all steps of the NO
      cGMP pathway. Homogenized tissue and purified enzyme were used to test effects of
      calmidazolium on sGC activity. KEY RESULTS: Inhibition of cGMP accumulation in
      the cells did not depend on changes in intracellular Ca(2+) concentration.
      Degradation of cGMP and inactivation of NO were both inhibited by the CaM
      antagonists, ruling out increased loss of cGMP or NO as explanations. Instead,
      calmidazolium directly inhibited purified sGC (IC(50)= 10 microM). The inhibition
      was not in competition with NO, nor did it arise from displacement of the haem
      moiety from sGC. Calmidazolium decreased enzyme V(max) and K(m), indicating that
      it acts in an uncompetitive manner. CONCLUSIONS AND IMPLICATIONS: The disruption
      of every stage of NO signal transduction by common CaM antagonists, unrelated to
      CaM antagonism, cautions against their utility as pharmacological tools. More
      positively, the compounds exemplify a novel class of sGC inhibitors that, with
      improved selectivity, may be therapeutically valuable.

PMID- 19845680
TI  - Beneficial effect of a hydrogen sulphide donor (sodium sulphide) in an ovine
      model of burn- and smoke-induced acute lung injury.
AB  - BACKGROUND AND PURPOSE: The present study investigated whether the
      pathophysiological changes induced by burn and smoke inhalation are modulated by
      parenteral administration of Na(2)S, a H(2)S donor. EXPERIMENTAL APPROACH: The
      study used a total of 16 chronically instrumented, adult female sheep. Na(2)S was
      administered 1 h post injury, as a bolus injection at a dose of 0.5 mg.kg(-1) and
      subsequently, as a continuous infusion at a rate of 0.2 mg.kg(-1).h(-1) for 24 h.
      Cardiopulmonary variables (mean arterial and pulmonary arterial blood pressure,
      cardiac output, ventricular stroke work index, vascular resistance) and arterial
      and mixed venous blood gases were measured. Lung wet-to-dry ratio and
      myeloperoxidase content and protein oxidation and nitration were also measured.
      In addition, lung inducible nitric oxide synthase expression and cytochrome c
      were measured in lung homogenates via Western blotting and enzyme-linked
      immunosorbent assay (elisa) respectively. KEY RESULTS: The H(2)S donor decreased
      mortality during the 96 h experimental period, improved pulmonary gas exchange
      and lowered further increase in inspiratory pressure and fluid accumulation
      associated with burn- and smoke-induced acute lung injury. Further, the H(2)S
      donor treatment reduced the presence of protein oxidation and 3-nitrotyrosine
      formation following burn and smoke inhalation injury. CONCLUSIONS AND
      IMPLICATIONS: Parenteral administration of the H(2)S donor ameliorated the
      pulmonary pathophysiological changes associated with burn- and smoke-induced
      acute lung injury. Based on the effect of H(2)S observed in this clinically
      relevant model of disease, we propose that treatment with H(2)S or its donors may
      represent a potential therapeutic strategy in managing patients with acute lung
      injury.

PMID- 19845681
TI  - Further pharmacological characterization of 5-HT(2C) receptor agonist-induced
      inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo.
AB  - BACKGROUND AND PURPOSE: Recent experiments using non-selective 5
      hydroxytryptamine (5-HT)(2C) receptor agonists including WAY 161503 suggested
      that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C)
      receptors, acting via neighbouring gamma-aminobutyric acid (GABA) neurones. The
      present study extended this pharmacological characterization by comparing the
      actions of WAY 161503 with the 5-HT(2C) receptor agonists, Ro 60-0275 and 1-(3
      chlorophenyl) piperazine (mCPP), as well as the non-selective 5-HT agonist
      lysergic acid diethylamide (LSD) and the 5-HT releasing agent 3,4
      methylenedioxymethamphetamine (MDMA). EXPERIMENTAL APPROACH: 5-HT neuronal
      activity was measured in the dorsal raphe nucleus (DRN) using extracellular
      recordings in anaesthetized rats. The activity of DRN GABA neurones was assessed
      using double-label immunohistochemical measurements of Fos and glutamate
      decarboxylase (GAD). KEY RESULTS: Ro 60-0175, like WAY 161503, inhibited 5-HT
      neurone firing, and the 5-HT(2C) antagonist SB 242084 reversed this effect. mCPP
      also inhibited 5-HT neurone firing ( approximately 60% neurones) in a SB 242084
      reversible manner. LSD inhibited 5-HT neurone firing; however, this effect was
      not altered by either SB 242084 or the 5-HT(2A/C) receptor antagonist ritanserin
      but was reversed by the 5-HT(1A) receptor antagonist WAY 100635. Similarly, MDMA
      inhibited 5-HT neurone firing in a manner reversible by WAY 100635, but not SB
      242084 or ritanserin. Finally, both Ro 60-0275 and mCPP, like WAY 161503,
      increased Fos expression in GAD-positive DRN neurones. CONCLUSIONS AND
      IMPLICATIONS: These data strengthen the hypothesis that midbrain 5-HT neurones
      are under the inhibitory control of 5-HT(2C) receptors, and suggest that the 5
      HT(2C) agonists Ro 60-0175, mCPP and WAY 161503, but not LSD or MDMA, are useful
      probes of the mechanism(s) involved.

PMID- 19845683
TI  - Mediators and receptors in the resolution of inflammation: drug targeting
      opportunities.
AB  - The active resolution of inflammation is recognized as offering new opportunities
      to generate novel anti-inflammatory agents. The emerging appreciation of the
      importance of active resolution in regulation of inflammation also creates an
      imperative to examine developing and existing agents for their potential to
      influence these pathways. This themed issue of the British Journal of
      Pharmacology contains papers that discuss the roles of annexin-1, lipoxins and
      related lipid products of fish oils as well as other mechanisms involved in
      active resolution and their receptor targets.

PMID- 19845682
TI  - NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels,
      enhances erectile responses in rats.
AB  - BACKGROUND AND PURPOSE: Large-conductance Ca(2+)-activated K(+) channels
      (BK(Ca)), located on the arterial and corporal smooth muscle, are potential
      targets for treatment of erectile dysfunction (ED). This study investigated
      whether NS11021 (1-(3,5-Bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1H-tetrazol-5
      yl)-phenyl]-thiourea), a novel opener of BK(Ca) channels, relaxes erectile tissue
      in vitro and enhances erectile responses in intact rats. The effects were
      compared with sildenafil, an inhibitor of phosphodiesterase type 5. EXPERIMENTAL
      APPROACH: Patch clamp was used to record whole cell current in rat isolated
      corpus cavernosum smooth muscle cells (SMCs) and human umbilical vein endothelial
      cells (HUVECs). Isometric tension was measured in intracavernous arterial rings
      and corpus cavernosum strips isolated from rats and men, and simultaneous
      measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension were
      performed in intracavernous arteries. Erectile response was measured in
      anaesthetized rats. KEY RESULTS: In patch clamp recordings, NS11021 increased
      currents sensitive to the selective BK(Ca) channel blocker, iberiotoxin (IbTX) in
      SMCs, but did not modulate K(+) current in HUVECs. NS11021 reduced [Ca(2+)](i)
      and tension in penile arteries. IbTX inhibited the vasorelaxation induced by
      NS11021 and sildenafil in human erectile tissue. NS11021 and sildenafil but not
      vehicle increased erectile responses in anaesthetized rats, an effect which was
      abolished after pretreatment with tetraethylammonium. CONCLUSIONS AND
      IMPLICATIONS: NS11021 leads to relaxation of both intracavernous arteries and
      corpus cavernosum strips primarily through opening of BK(Ca) channels. It is also
      effective in facilitating erectile responses in anaesthetized rats. These results
      suggest a potential for use of BK(Ca) openers in the treatment of ED.

PMID- 19845684
TI  - Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory
      therapeutics.
AB  - The appreciation that the inflammatory reaction does not 'spontaneously' finish,
      but rather that inflammatory resolution is an active phenomenon brought about by
      endogenous anti-inflammatory agonists opens multiple opportunities for a
      reassessment of the complexity of inflammation and its main mediators. This
      review dwells on one of these pathways, the one centred around the glucocorticoid
      regulated protein Annexin A1 and its G protein-coupled receptor. In recent years,
      much of the knowledge detailing the processes by which Annexin A1 expresses its
      anti-inflammatory role on innate immunity has been produced. Moreover, the
      generation of the Annexin A1 null mouse colony has provided important proof-of
      concept experiments demonstrating the inhibitory properties of this mediator in
      the context of inflammatory and/or tissue-injury models. Therefore, Annexin A1
      acts as a pivotal homeostatic mediator, where if absent, inflammation would
      overshoot and be prolonged. This new understanding scientific information could
      guide us onto the exploitation of the biological properties of Annexin A1 and its
      receptor to instigate novel drug discovery programmes for anti-inflammatory
      therapeutics. This line of research relies on the assumption that anti
      inflammatory drugs designed upon endogenous anti-inflammatory mediators would be
      burdened by a lower degree of secondary effects as these agonists would be
      mimicking specific pathways activated in our body for safe disposal of
      inflammation. We believe that the next few years will produce examples of such
      new drugs and the validity of this speculation could then be assessed.

PMID- 19845687
TI  - Lipid mediator interplay: resolvin D1 attenuates inflammation evoked by
      glutathione-conjugated lipid peroxidation products.
AB  - Non-enzymatic oxidation of cellular lipids, one of the characteristic features of
      inflammation, leads to formation of highly reactive and toxic alpha,beta
      unsaturated aldehydes, such as 4-hydroxy-trans-2-nonenal (HNE). Conjugation of
      HNE with reduced glutathione (GS-HNE) is widely believed to represent a form of
      detoxification. The study by Spite et al. in the current issue of the British
      Journal of Pharmacology shows that glutathiolation of HNE confers potent pro
      inflammatory properties on this alpha,beta-unsaturated aldehyde. They find that
      GS-HNE directly activates human neutrophil granulocytes in vitro and evokes
      peritonitis in mice. Pre-treatment with resolvin D1, which is derived from omega
      3 fatty acids, markedly attenuated the peritoneal leukocyte accumulation and
      production of prostaglandins and leukotrienes induced by GS-HNE. Their findings
      have profound implications for the analysis of inflammation in describing the
      generation of a novel class of pro-inflammatory mediators, through glutathione
      dependent metabolism of lipid-peroxidation products, and emphasize the
      therapeutic potential of resolvin D1 in inflammatory diseases.

PMID- 19845686
TI  - Proteases and antiproteases in chronic neutrophilic lung disease - relevance to
      drug discovery.
AB  - Chronic inflammatory lung diseases such as cystic fibrosis and emphysema are
      characterized by higher-than-normal levels of pulmonary proteases. While these
      enzymes play important roles such as bacterial killing, their dysregulated
      expression or activity can adversely impact on the inflammatory process. The
      existence of efficient endogenous control mechanisms that can dampen or halt this
      overexuberant protease activity in vivo is essential for the effective resolution
      of inflammatory lung disease. The function of pulmonary antiproteases is to
      fulfil this role. Interestingly, in addition to their antiprotease activity,
      protease inhibitors in the lung also often possess other intrinsic properties
      that contribute to microbial killing or termination of the inflammatory process.
      This review will outline important features of chronic inflammation that are
      regulated by pulmonary proteases and will describe the various mechanisms by
      which antiproteases attempt to counterbalance exaggerated protease-mediated
      inflammatory events. These proteases, antiproteases and their modifiers represent
      interesting targets for therapeutic intervention.

PMID- 19845688
TI  - Expression and role of Oct3/4, Nanog and Sox2 in regeneration of rat tracheal
      epithelium.
AB  - OBJECTIVES: To explore the role of Oct3/4, Nanog and Sox2 in regeneration of rat
      tracheal epithelium. MATERIALS AND METHODS: An ex vivo model of rat tracheal
      epithelial regeneration using 5-fluorouracil (5-FU) was developed, to induce
      injury. Expression levels of Oct3/4, Nanog and Sox2 were examined using Western
      blot analysis, RT-PCR or microscopically observed immunofluorescence, and cell
      morphological changes were observed using HE staining, during the recovery
      process. RESULTS: Oct3/4, Nanog and Sox2 were not detectable in normal tracheal
      epithelium. After treatment with 5-FU, the normally proliferating tracheal
      epithelium desquamated and only a few cells in G0 phase of the cell cycle were
      left on the basement membrane and Oct3/4, Nanog and Sox2 could be observed at
      this time. Thereafter, the number of Oct3/4-, Nanog- and Sox2-positive cells
      increased gradually. When the cells differentiated into ciliate cells, mucous
      cells or basal cells, and restored pseudostratified mucociliary epithelium, the
      number of Oct3/4-, Nanog- and Sox2-positive cells decreased and gradually
      disappeared. CONCLUSIONS: G0 phase cells with resistance to 5-FU damage expressed
      Oct3/4, Nanog and Sox2. This indicated that these cells were undifferentiated,
      but had the ability to terminally differentiate into downstream-type cells. They
      possessed stem cell properties. The results are consistent with Oct3/4, Nanog and
      Sox2-expressing cells being considered as tracheal stem cells.

PMID- 19845689
TI  - Heparin regulates colon cancer cell growth through p38 mitogen-activated protein
      kinase signalling.
AB  - OBJECTIVES: Heparin acts as an extracellular stimulus capable of activating major
      cell signalling pathways. Thus, we examined the putative mechanisms utilized by
      heparin to stimulate HT29, SW1116 and HCT116 colon cancer cell growth. MATERIALS
      AND METHODS: Possible participation of the mitogen-activated protein kinase
      (MAPK) cascade on heparin-induced HT29, SW1116 and HCT116 colon cancer cell
      growth was evaluated using specific MAPK cascade inhibitors, Western blot
      analysis, real-time quantitative PCR and FACS apoptosis analysis. RESULTS:
      Treatment with a highly specific p38 kinase inhibitor, SB203580, significantly
      (50-70%) inhibited heparin-induced colon cancer cell growth, demonstrating that
      p38 MAPK signalling is involved in their heparin-induced proliferative response.
      This was shown to be correlated with increased (up to 3-fold) phosphorylation of
      181/182 threonine/tyrosine residues on p38 MAP kinase. Furthermore, heparin
      inhibited cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and p53 tumour
      suppressor gene and protein expression up to 2-fold or 1.8-fold, respectively,
      and stimulated cyclin D1 expression up to 1.8-fold, in these cell lines through a
      p38-mediated mechanism. On the other hand, treatment with heparin did not appear
      to affect HT29, SW1116 and HCT116 cell levels of apoptosis. CONCLUSIONS: This
      study demonstrates that an extracellular glycosaminoglycan, heparin, finely
      modulates expression of genes crucial to cell cycle regulation through specific
      activation of p38 MAP kinase to stimulate colon cancer cell growth.

PMID- 19845690
TI  - CFTR mutations in cystic fibrosis patients from Murcia region (southeastern
      Spain): implications for genetic testing.

PMID- 19845685
TI  - Protease-activated receptors and prostaglandins in inflammatory lung disease.
AB  - Protease-activated receptors (PARs) are a novel family of G protein-coupled
      receptors. Signalling through PARs typically involves the cleavage of an
      extracellular region of the receptor by endogenous or exogenous proteases, which
      reveals a tethered ligand sequence capable of auto-activating the receptor. A
      considerable body of evidence has emerged over the past 20 years supporting a
      prominent role for PARs in a variety of human physiological and
      pathophysiological processes, and thus substantial attention has been directed
      towards developing drug-like molecules that activate or block PARs via non
      proteolytic pathways. PARs are widely expressed within the respiratory tract, and
      their activation appears to exert significant modulatory influences on the level
      of bronchomotor tone, as well as on the inflammatory processes associated with a
      range of respiratory tract disorders. Nevertheless, there is debate as to whether
      the principal response to PAR activation is an augmentation or attenuation of
      airways inflammation. In this context, an important action of PAR activators may
      be to promote the generation and release of prostanoids, such as prostglandin
      E(2), which have well-established anti-inflammatory effects in the lung. In this
      review, we primarily focus on the relationship between PARs, prostaglandins and
      inflammatory processes in the lung, and highlight their potential role in
      selected respiratory tract disorders, including pulmonary fibrosis, asthma and
      chronic obstructive pulmonary disease.

PMID- 19845692
TI  - Emergence of Crimean-Congo haemorrhagic fever in Greece.
AB  - In the summer of 2008, the first case of Crimean-Congo haemorrhagic fever (CCHF)
      was observed in Greece. The laboratory diagnosis was established using nested RT
      PCR and quantitative real-time RT-PCR. A high viral load and increased levels of
      cytokines were detected on the third day of illness and the patient died 7 days
      after the onset of symptoms. Nucleotide sequence analysis revealed that the Greek
      CCHF virus strain had high sequence identity with other Balkan CCHF virus
      strains.

PMID- 19845691
TI  - Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in
      NF1.
AB  - Noonan syndrome (NS) and neurofibromatosis type I (NF1) belong to a group of
      clinically related disorders that share a common pathogenesis, dysregulation of
      the RAS-MAPK pathway. NS is characterized by short stature, heart defect, pectus
      deformity and facial dysmorphism, whereas skin manifestations, skeletal defects,
      Lisch nodules and neurofibromas are characteristic of NF1. Both disorders display
      considerable clinical variability. Features of NS have been observed in
      individuals with NF1 -a condition known as neurofibromatosis-Noonan syndrome
      (NFNS). The major gene causing NFNS is NF1. Rarely, a mutation in PTPN11 in
      addition to an NF1 mutation is present. We present the clinical and molecular
      characterization of a family displaying features of both NS and NF1, with
      complete absence of neurofibromas. To investigate the etiology of the phenotype,
      mutational analysis of NF1 was conducted, revealing a novel missense mutation in
      exon 24, p.L1390F, affecting the GAP-domain. Additional RAS-MAPK pathway genes
      were examined, but no additional mutations were identified. We confirm that NF1
      mutations are involved in the etiology of NFNS. Furthermore, based on our results
      and previous studies we suggest that evaluation of the GAP-domain of NF1 should
      be prioritized in NFNS.

PMID- 19845693
TI  - Molecular epidemiology of the nasal colonization by methicillin-susceptible
      Staphylococcus aureus in Swiss children.
AB  - Nasal carriage of Staphylococcus aureus contributes to an increased risk of
      developing an infection with the same bacterial strain. Genetic regulatory
      elements and toxin-expressing genes are virulence factors associated with the
      pathogenic potential of S. aureus. We undertook an extensive molecular
      characterization of methicillin-susceptible S. aureus (MSSA) carried by children.
      MSSA were recovered from the nostrils of children. The presence of Panton
      Valentine leukocidin (PVL), exfoliatins A and B (exfoA and exfoB), and the toxic
      shock staphylococcal toxin (TSST-1) and agr group typing were determined by
      quantitative PCR. A multiple-locus variable-number of tandem repeat analysis
      (MLVA) assay was also performed for genotyping. Five hundred and seventy-two
      strains of MSSA were analysed. Overall, 30% were positive for toxin-expressing
      genes: 29% contained one toxin and 1.6% two toxins. The most commonly detected
      toxin gene was tst, which was present in 145 (25%) strains. The TSST-1 gene was
      significantly associated with the agr group 3 (OR 56.8, 95% CI 32.0-100.8). MLVA
      analysis revealed a large diversity of genetic content and no clonal relationship
      was demonstrated among the analysed MSSA strains. Multilocus sequence typing
      confirmed this observation of diversity and identified ST45 as a frequent
      colonizer. This broad diversity in MSSA carriage strains suggests a limited
      selection pressure in our geographical area.

PMID- 19845694
TI  - Epidemiology and clinical features of community-acquired, healthcare-associated
      and nosocomial bloodstream infections in tertiary-care and community hospitals.
AB  - Classification of bloodstream infections (BSIs) as community-acquired (CA),
      healthcare-associated (HCA) and hospital-acquired (HA) has been proposed. The
      epidemiology and clinical features of BSI according to that classification in
      tertiary-care (TH) and community (CH) hospitals were investigated in a
      prospective cohort of 821 BSI episodes from 15 hospitals (ten TH and five CH
      hospitals) in Andalucia, Spain. Eighteen percent were CA, 24% were HCA and 58%
      were HA. The incidence of CA and HCA BSI was higher in CH than in TH (CA: 3.9
      episodes per 1000 admissions vs. 2.2, p <0.01; HCA: 5.0 vs. 2.9, p <0.01),
      whereas the incidence of HA BSI was lower (7.7 vs. 8.7, p <0.01). In CA and HCA
      BSI, the respiratory tract was more frequently the source in CH than in TH (CA:
      30% vs. 15%; HCA: 20% vs. 9%, p <=0.03). In HCA BSI, chronic renal insufficiency
      and tunnelled catheters were less frequent in CH than in TH (11% vs. 26% and 7%
      vs. 19%, p <=0.03), although chronic ulcers were more frequent (22% vs. 8%, p
      0.008). BSIs as a result of methicillin-resistant Staphylococcus aureus or
      Pseudomonas aeruginosa were very rare in CA episodes, although extended-spectrum
      b-lactamase-producing Escherichia coli (ESBLEC) caused a similar proportion of
      all BSIs in CA, HCA and HA episodes. Multivariate analysis revealed no
      significant difference in mortality rates in CH and TH. HCA infections should be
      considered as a separate class of BSI in both TH and CH, although differences
      between hospitals must be considered. CA BSIs were not caused by multidrug
      resistant pathogens, except for ESBLEC.

PMID- 19845695
TI  - Do clinicians consider the results of the BinaxNOW Streptococcus pneumoniae
      urinary antigen test when adapting antibiotic regimens for pneumonia patients?
AB  - The BinaxNOW Streptococcus pneumoniae urinary antigen test is a rapid and
      reliable immunochromatographic test (ICT) for the identification of a
      pneumococcal aetiology of pneumonia. The aim of this study was to evaluate the
      attitude of clinicians in their everyday practice towards prescription of the ICT
      and the impact of its results on the adaptation of the antibiotic therapy when
      pneumonia is suspected. From October 2007 to March 2008, we prospectively
      evaluated 541 consecutive inpatients for whom the ICT was performed in our
      institution. Of the 541 patients evaluated, only 233 (43%) were suspected by the
      treating physicians to have a pneumonia, 58 of whom had a positive ICT result.
      Among these 58 patients, four (7%) and 26 (45%), respectively, were treated with
      amoxycillin monotherapy before and after the ICT result had been obtained (p <10(
      4)). Although a positive ICT result led to a rise in the proportion of patients
      treated with amoxycillin alone, a large number continued to be treated with
      broader-spectrum antibiotics. These results suggest that prescription monitoring
      of the ICT should be implemented along with encouragement to adhere more strictly
      to treatment guidelines.

PMID- 19845696
TI  - First report of molecular characterization of fluoroquinolone-resistant
      Mycobacterium tuberculosis isolates from a Tunisian hospital.
AB  - Fluoroquinolones are increasingly used for the treatment of infections caused by
      multidrug-resistant Mycobacterium tuberculosis. Our study was designed to
      determine the frequency of the emergence of ciprofloxacin-resistant isolates in a
      university hospital (Rabta University Hospital Tunis, Tunisia) and to
      characterize the mutations responsible for the resistance phenotype. A total of
      495 clinical M. tuberculosis isolates obtained from January 2005 to July 2008
      were investigated for their susceptibility to ciprofloxacin, using the standard
      proportion method, PCR and DNA sequencing. Four resistant isolates (0.8%) were
      identified. Among these, only two carried point mutations in gyrA leading to
      amino acid changes other than the phenotypically silent S95T substitution. No
      gyrB missense mutations were found in any of the clinical isolates. Although
      fluoroquinolone resistance is still rare in Tunisia, accurate surveillance is
      needed in order to control the possible emergence of resistance to
      fluoroquinolones, which are essential for the successful treatment of multidrug
      resistant tuberculosis.

PMID- 19845697
TI  - Osteoarticular tuberculosis in Tehran, Iran: a 2-year study.
AB  - Osteoarticular tuberculosis (TB) accounts for 1-5% of all TB cases and 10-18% of
      those with extrapulmonary infection. Diagnosis is difficult, because the lungs
      are rarely involved and there are no specific signs or symptoms. The purpose of
      this study was to assess the frequency and clinical and laboratory findings in
      osteoarticular TB in two referral hospitals in Tehran, Iran. The hospital dataset
      of patients admitted with osteoarticular TB during 2003-2005 was reviewed.
      Patients' demographic data, clinical presentation and radiological and
      pathological findings were analysed. Weight loss (50%), fever (36%) and night
      sweats (38.5%) were the most common constitutional symptoms. Knee, ankle, hip and
      shoulder joints were the most frequent sites for TB arthritis. In osteomyelitis,
      long and short bones were equally affected. In TB spondylitis, the lumbar (22.7%)
      and thoracic (50%) vertebrae were the most commonly involved sites. The most
      frequently reported complications were sphincter disorder (39.1%), paraplegia
      (28.9%) and kyphosis (19.3%). TB osteomyelitis must always be borne in mind in
      countries where TB has high prevalence.

PMID- 19845698
TI  - Voriconazole concentrations and outcome of invasive fungal infections.
AB  - Twenty-five patients with proven or probable invasive fungal infections (IFIs)
      who experienced two or more episodes of voriconazole therapeutic drug monitoring
      (TDM) at a tertiary referral hospital were reviewed to explore the association
      between serum trough concentrations and outcomes of IFI. Microbiological and/or
      clinical success, in addition to IFI-related mortality, was assessed. We
      performed two separate analyses, one based on the initial trough voriconazole
      concentration at steady state, and the other on the median trough voriconazole
      concentration (derived from repeated TDM episodes) for each patient. Large
      interpatient and intrapatient variability of trough plasma voriconazole
      concentrations was observed, with no correlation between dose and concentration
      (r = 0.065). Classification and regression tree analysis revealed an association
      between IFI-related mortality and initial trough voriconazole concentrations,
      with patients more likely to die when their initial steady-state concentration
      was <=0.35 mg/L (p 0.004; OR 11, 95% CI 2.9-41.2). Successful outcomes were more
      likely among patients with a median trough voriconazole concentration >2.2 mg/L
      (p 0.003; OR 2.7, 95% CI 1.4-5). Nineteen adverse events, with four severe
      events, were documented in 14 patients. Patients with severe adverse events had
      higher median voriconazole concentrations than the remaining cohort (2.38 mg/L
      vs. 1.30 mg/L; p <0.04). All adverse events resolved after cessation of
      voriconazole treatment. Our data suggest that voriconazole TDM is appropriate for
      all patients as soon as steady state is achieved. For non-responding patients
      with low trough concentrations, the association with IFI-related mortality
      indicates the need for dose adjustments to achieve and sustain voriconazole
      concentrations.

PMID- 19845699
TI  - Out-of-water: emerging, nontuberculous mycobacteria.

PMID- 19845700
TI  - Environmental sources of rapid growing nontuberculous mycobacteria causing
      disease in humans.
AB  - Nontuberculous mycobacteria are environmental, opportunistic pathogens whose role
      in human disease is increasingly recognized, especially regarding the rapid
      growing mycobacteria (RGM). RGM are recovered from various environmental sources,
      both natural and man-made. In water systems, RGM can survive by forming biofilms
      and by interactions with protozoa. The presence and species diversity of RGM in
      water is influenced by temperature, pH and the chemical quality of the water, as
      well as the availability of nutrients, although the exact correlations remain
      controversial. Despite their omnipresence in environmental sources, the actual
      transmission of RGM to humans, with subsequent clinical disease, has rarely been
      proven. However, outbreaks as a result of contaminated water sources have been
      reported, although accidental presence in clinical samples cannot always be
      excluded. In this setting, the presence of RGM does not necessarily indicate a
      causal relationship with clinical disease; accidental presence in clinical
      samples cannot always be excluded. Future studies should focus on the exact
      environmental sources of infection, aiming to examine possibilities for
      prevention of infections in patients at risk. Furthermore, studies should focus
      on the actual sites of the active replication of RGM; their presence may not
      indicate their natural habitat.

PMID- 19845701
TI  - Free-living amoebae, a training field for macrophage resistance of mycobacteria.
AB  - Mycobacterium species evolved from an environmental recent common ancestor by
      reductive evolution and lateral gene transfer. Strategies selected through
      evolution and developed by mycobacteria resulted in resistance to predation by
      environmental unicellular protists, including free-living amoebae. Indeed,
      mycobacteria are isolated from the same soil and water environments as are
      amoebae, and experimental models using Acanthamoeba spp. and Dictyostelium
      discoideum were exploited to analyse the mechanisms for intracellular survival.
      Most of these mechanisms have been further reproduced in macrophages for
      mycobacteria regarded as opportunistic and obligate pathogens. Amoebal cysts may
      protect intracellular mycobacteria against adverse conditions and may act as a
      vector for mycobacteria. The latter hypothesis warrants further environmental and
      clinical studies to better assess the role of free-living amoebae in the
      epidemiology of infections caused by mycobacteria.

PMID- 19845702
TI  - Clinical manifestations of nontuberculous mycobacteria infections.
AB  - The isolation of nontuberculous mycobacteria (NTM) from clinical specimens has
      become very frequent in the last years. Such organisms are typically
      environmental and poorly pathogenic for humans; they can, however, be responsible
      for opportunistic diseases in subjects presenting with various predisposing
      conditions. Pulmonary infections are responsible for the most frequent disease
      caused by NTM, although the relevance of mycobacterioses involving other parts of
      the body is increasing. The risk of disseminated infections characterizing
      immunocompromised patients is well known, and those numbers are steadily rising.
      The lymph nodes, cutis and soft tissues, as well as bone and joints, are also
      important targets of NTM infection. The problems concerning the assessment of the
      clinical significance of NTM, along with a consideration of the more frequent NTM
      pathologies, are the major objectives of this review.

PMID- 19845703
TI  - Mycobacterium mucogenicum group infections: a review.
AB  - It has become apparent that Mycobacterium mucogenicum isolates recovered from
      clinical samples are more diverse than was previously realized and include an
      increasing number of emerging pathogens, as depicted by multilocus sequence
      analysis. Most clinically significant cases of those organisms involved catheter
      related infections. They are susceptible to most antimicrobial agents, but like
      other rapidly growing mycobacteria, they are resistant to first-line
      antituberculous agents. A review of the cases of M. mucogenicum complex infection
      in the literature is addressed here, as well as two additional cases of the
      closely related species Mycobacterium aubagnense.

PMID- 19845704
TI  - Seasonal variation in Escherichia coli bloodstream infection: a population-based
      study.
AB  - Seasonal variation in the rates of infection with certain Gram-negative organisms
      has been previously examined in tertiary-care centres. We performed a population
      based investigation to evaluate the seasonal variation in Escherichia coli
      bloodstream infection (BSI). We identified 461 unique patients in Olmsted County,
      Minnesota, from 1 January 1998 to 31 December 2007, with E. coli BSI. Incidence
      rates (IR) and IR ratios were calculated using Rochester Epidemiology Project
      tools. Multivariable Poisson regression was used to examine the association
      between the IR of E. coli BSI and average temperature. The age- and gender
      adjusted IR of E. coli BSI per 100 000 person-years was 50.2 (95% CI 42.9-57.5)
      during the warmest 4 months (June through September) compared with 37.1 (95% CI
      32.7-41.5) during the remainder of the year, resulting in a 35% (95% CI 12-66%)
      increase in IR during the warmest 4 months. The average temperature was
      predictive of increasing IR of E. coli BSI (p 0.004); there was a 7% (95% CI 2
      12%) increase in the IR for each 10-degree Fahrenheit (c. 5.5 degrees C) increase
      in average temperature. To our knowledge, this is the first study to demonstrate
      seasonal variation in E. coli BSI, with a higher IR during the warmest 4 months
      than during the remainder of the year.

PMID- 19845705
TI  - Seasonal peaks in Escherichia coli infections: possible explanations and
      implications.
AB  - Escherichia coli is a common cause of infections in all populations and countries
      of the world, causing an enormous burden of disease. In this issue of Clinical
      Microbiology and Infection, Al-Hasan et al. describe seasonal peaks in the
      incidence of E. coli bloodstream infection (BSI) during the summer for a
      population of 125 000 in Minnesota, USA. We discuss the probability that similar
      seasonal peaks in the incidence of E. coli BSI occur in other populations and
      geographical regions. Second, we discuss possible underlying explanations for
      these findings in terms of seasonal changes in human behaviour and the effect of
      temperature on the ability of E. coli to survive in the environment. Finally, we
      discuss some of the possible implications of E. coli BSI being a seasonal
      illness. More specifically, we discuss how better understanding the reasons for
      seasonality may potentially help us to better understand the dominant routes by
      which human populations are exposed to clonal groups of E. coli associated with
      urinary tract infection.

PMID- 19845706
TI  - On cone-beam computed tomography artifacts induced by titanium implants.
AB  - OBJECTIVES: To briefly review the mathematical background of beam-hardening
      artifacts in cone-beam computed tomography (CBCT)-reconstruction and to
      investigate geometrical properties relevant for these reconstruction errors. By
      means of simulated and experimental results, beam-hardening effects caused by
      titanium implants are evaluated. MATERIALS AND METHODS: The geometrical and
      physical properties of the acquisition process of the projections used for 3D
      reconstruction are investigated and their effects on the CBCT images in the
      presence of titanium implants are derived. Beam-hardening effects are computed
      for a simplified polychromatic situation (three energy subsets of 80 and 110 kV)
      and compared with experimental results from a hard-plaster phantom containing two
      'implants' (pure titanium rods; 4 mm diameter) exposed in two CBCT machines.
      RESULTS: Massive absorption within a typical implant body (diameter: 4 mm) was
      computed for the low-energy subset of both energies (80 kV: 99.7%; 110 kV:
      90.9%), whereas the high-energy subsets are only marginally absorbed (80 kV:
      14.8%; 110 kV: 11.3%). Accordingly, phantom data revealed drastically reduced
      gray values in artifact-affected regions (3DAccuitomo: -46% to -51%) or (3DExam: 
      55%) plus increased noise (+67% vs. +73%), when compared with unaffected regions.
      CONCLUSIONS: Our theoretical and experimental results prove massive beam
      hardening artifacts for a typical implant diameter and typical energies of up-to
      date CBCT machines. Meaningful artifact reduction has to be based on more
      sophisticated mathematical modeling of the actual physical image acquisition
      process rather than on postprocessing of the erroneous results obtained from the
      rather crude reconstruction algorithms used presently.

PMID- 19845707
TI  - Histomorphometric comparison of maxillary pristine bone and composite bone graft
      biopsies obtained after sinus augmentation.
AB  - INTRODUCTION: Sinus grafting is a technique oriented to facilitate implant
      placement in posterior atrophic maxillae. Several modifications of the original
      technique and a wide variety of materials have been proposed; most of them
      associated with implant survival rates. However, the quality of the bone obtained
      after the application of certain grafting materials has not been fully elucidated
      yet. The aims of this multicenter study were to analyse histomorphometrical
      samples obtained 6 months after sinus grafting using a composite graft consisting
      of anorganic bovine bone (ABB)+ autologous bone (AB), and to compare these
      samples with maxillary pristine bone biopsies. MATERIAL AND METHODS: Ninety
      maxillary sinus augmentations were performed for delayed implant placement (N =
      90) in 45 consecutive patients (test group). Bone cores were harvested 6 months
      after grafting for histomorphometric and ultrastructural study. Control pristine
      bone biopsies were taken from the posterior maxilla of 10 patients (control).
      Bone radiographic changes were assessed up to 24 months after implant loading.
      RESULTS: The total mean values after analysis of test cores revealed a proportion
      of 46.08 + or - 16.6% of vital bone, 42.27 + or - 15.1% of non-mineralized
      connective tissue, and 37.02 + or - 25.1% of the remaining ABB particles.
      Significant bone remodeling activities were noticed in sinus grafting samples
      when compared with pristine bone. A statistically significant difference was
      observed in the number of osteoid lines between two groups, with higher values in
      the test one (15.1 + or - 11.48% vs. 2.5 + or - 2.2%, P = 0.0005).
      Ultrastructural study showed that vital trabecular bone was in intimal contact
      with ABB particles. Radiographic analysis revealed that the higher the proportion
      of remaining ABB, the lower the total vertical resorption of the graft.
      CONCLUSION: Sinus grafting constitutes an excellent model for the study of de
      novo bone formation patterns and graft consolidation, when a combination of
      different bone substitutes is applied. The combination of ABB+AB yields highly
      satisfactory outcomes from both a clinical and a histologic perspective.

PMID- 19845708
TI  - Functional aspects of treatment with implant-supported single crowns: a quality
      control study in subjects with tooth agenesis.
AB  - BACKGROUND: No comprehensive patient-centered and clinical evaluations of the
      functional effect of treatment with implant-supported single crowns (ISSC) have
      been reported previously. OBJECTIVE: To investigate whether and how treatment
      with ISSC affects masticatory function and Oral Health-Related Quality of Life
      (OHRQoL) in subjects with tooth agenesis. MATERIAL AND METHODS: In nine females
      and nine males (32 + or - 10 years) with agenesis treated with one to four ISSC
      (68% in the premolar region), the treatment effect and masticatory function were
      assessed. The evaluation was performed first after implant placement shortly
      before crown cementation, and again 1 month after cementation. It consisted of
      questionnaires [including Oral Health Impact Profile (OHIP-49)] and functional
      examination with plastic strips, the Dental Prescale Film and the Occluzer
      system, Xylitol color-changeable gum and slices of Granny Smith apple. RESULTS:
      The patients' satisfaction with treatment was high and they experienced a
      significant overall improvement in their OHRQoL (on average 13% reduction in the
      total OHIP scores). The cementation of the crowns was associated with a
      significant increase in the number of near occlusal tooth contacts, contact area,
      bite force, and masticatory ability and performance. Correspondingly, there was a
      significant, positive correlation between the number of tooth contacts and (1)
      occlusal contact area, (2) bite force, and (3) masticatory performance.
      CONCLUSION: Treatment with ISSCs in subjects with tooth agenesis significantly
      increased masticatory function subjectively and clinically as well as OHRQoL.
      However, as the functional parameters before replacement of the teeth
      corresponded to values in subjects with complete dentitions, the functional
      importance of the increase may be questioned.

PMID- 19845709
TI  - Oral health-related quality of life of 12- and 15-year-old Thai children:
      findings from a national survey.
AB  - OBJECTIVE: To assess the prevalence and characteristics of oral impacts on daily
      life, and the relationship between certain dental conditions and impacts
      attributed to them, in a nationally representative population of Thai school
      children aged 12 and 15 years. METHODS: A cross-sectional study on a
      representative sample of children in Sixth Thailand National Oral Health Survey.
      Sample included half the children aged 12- and 15-year-old selected in Bangkok
      and all participants in 8 of 16 provinces included in national survey. Children
      were individually interviewed using the Child-OIDP (12-year-old) and OIDP indices
      (15-year-old), and two questions for overall subjective assessments. RESULTS: A
      total of 1066 12-year-olds and 815 15-year-olds were interviewed. Some 85.2% of
      12-year-olds reported experiencing oral impacts during the past 3 months. Child
      OIDP scores ranged from 0 to 68.0 (mean = 7.83, SD = 7.8). Eating was the most
      commonly affected performance (64.4%), followed by cleaning teeth (51.7%) and
      maintaining emotional state (49.1%). Among 15-year-old children, 83.3% had oral
      impacts during the past 6 months. OIDP scores ranged from 0 to 39.5 (mean = 5.47,
      SD = 6.0). The three most commonly affected performances were eating (64.0%),
      cleaning teeth (55.3%) and maintaining emotional state (53.1%). Toothache and
      oral ulcers were the two most important perceived causes in 12-year-olds. Impacts
      from toothache were the most prevalent (39.2%) and had a condition-specific (CS)
      Child-OIDP score of 7.0, while oral ulcers affected 24.7% of children; mean CS
      score of 8.0. Among 15-year-olds, oral ulcers ranked first in terms of both
      prevalence (36.2%) and CS-score (6.0), followed by toothache (prevalence 33.9%
      and CS-score 5.0). For both age groups, problems with gums were of less concern.
      CONCLUSIONS: Oral impacts were common but not severe in Thai children and
      adolescents. For both age groups, impacts were mostly on eating performance;
      toothache and oral ulcers were the two important perceived causes reflecting
      needs for oral health promotion and treatment of dental caries and oral ulcers.

PMID- 19845710
TI  - Caries and background factors in Norwegian and immigrant 5-year-old children.
AB  - OBJECTIVES: The purpose of this study was to assess the caries status of 5-year
      olds in a low caries area, and study associations between dental caries and
      parent-related factors: parents' education, national origin, oral health
      behaviours and attitudes. METHODS: The material consisted of 523 children and was
      a stratified random sample. Clinical and radiographic examination was performed
      in 2007. Enamel and dentine caries were recorded at surface level. Parents filled
      in questionnaires regarding socioeconomic status, their own oral health
      behaviours and attitudes. RESULTS: Most participants (66%) had no caries
      experience and 16% had enamel caries only. Dentine caries experience was present
      in 18% of the children, and 5% had dentine caries experience in five or more
      teeth. Surfaces with enamel caries constituted half of all surfaces with caries
      experience. In multiple logistic regression, statistically significant risk
      indicators for the child having dentine caries experience at the age of five
      were: having one or both parents of non-western origin (OR = 4.8), both parents
      (OR = 3.0) or one parent (OR = 2.1) with low education, parental laxness about
      the child's tooth brushing (OR = 2.8), parents' brushing their own teeth less
      than twice a day (OR = 2.2) and having parents with frequent sugar intakes (OR =
      1.8). CONCLUSION: Caries prevalence in 5-year-olds was strongly associated with
      parent-related factors signifying that information on parents' socioeconomic
      status, dental behaviours and attitudes should be considered when planning dental
      services for young children. Our results suggest that the real high risk group is
      non-western children whose parents have low education.

PMID- 19845711
TI  - Socioeconomic factors in adolescents' oral health: are they mediated by oral
      hygiene behaviors or preventive interventions?
AB  - OBJECTIVES: To determine whether there is a socioeconomic status (SES) disparity
      in caries experience (i.e., DMFT) in an adolescent sample from Pennsylvania and
      to determine whether differences in oral hygiene behaviors and preventive
      interventions account for this disparity. METHODS: A cross-sectional clinical
      assessment was conducted on a representative sample of 9th grade and 11th grade
      students across Pennsylvania. These students also completed a brief questionnaire
      regarding their oral hygiene behaviors. From this group of students, a random
      subsample of 530 parents completed a questionnaire assessing SES, fluoride
      exposure, and recency of receipt of dental services. DMFT was examined at two
      thresholds of severity: simple prevalence (DMFT > 0) and severe caries (DMFT >
      3). RESULTS: Using structural equation modeling, we found that lower SES was
      associated with higher prevalence of DMFT and higher prevalence of severe caries.
      Although lower SES was associated with lower rates of brushing, less use of
      sealants, and less recent receipt of dental services, these oral health behaviors
      and preventive interventions did not account for the disparities in DMFT defined
      by SES. CONCLUSIONS: There is an SES gradient in caries experience in adolescents
      in Pennsylvania. Disparities in caries experience, however, cannot be accounted
      for by SES-associated differences in brushing, flossing, sealant use, fluoride
      exposure, or recency of use of dental services. To facilitate the design of
      preventive interventions, future research should determine the pathways through
      which SES-associated disparities occur.

PMID- 19845712
TI  - Applying Andersen's behavioural model to oral health: what are the contextual
      factors shaping perceived oral health outcomes?
AB  - OBJECTIVES: Andersen's revised behavioural model provides a framework for
      understanding the factors which influence utilization of health services and key
      health outcomes. To date, there have been few studies that have explicitly tested
      the model in relation to oral health. The aim of this study was to test the model
      and to examine the direct and mediated pathways between social, attitudinal and
      behavioural factors and perceived oral health outcomes. METHODS: The model was
      tested in a general population sample with data from the UK adult dental health
      survey (N = 3815) using the two-stage process of structural equation modelling.
      RESULTS: Structural equation modelling indicated support in line with the
      hypotheses within the model; enabling resources (oral health education advice,
      type of dental service, finding NHS treatment expensive, dental anxiety)
      predicted need (number of decayed or unsound teeth and perceived treatment need);
      enabling resources and need predicted personal health practices and use of
      services (frequency of toothbrushing, recent dental attendance, attendance
      orientation) which, in turn, predicted perceived oral health outcomes (oral
      health quality of life). Both enabling resources and need also predicted
      perceived oral health outcomes. The impact of predisposing factors (social class,
      qualifications, income) on need, personal health practices and use of services,
      and oral health outcomes was indirect; that is, mediated by intervening factors.
      In the final model, 26%, 37%, 49% and 21% of the variance was accounted for in
      enabling resources, treatment need, personal health practices and use of services
      and perceived oral health outcomes respectively. CONCLUSION: The results provide
      support for Andersen's behavioural model as applied to perceived oral health.
      Further conceptual development of the model is discussed.

PMID- 19845713
TI  - Adolescent toothbrushing and the home environment: sociodemographic factors,
      family relationships and mealtime routines and disorganisation.
AB  - OBJECTIVES: Previous studies have shown that sociodemographic factors are
      associated with adolescent toothbrushing. While there has been some investigation
      of parental modelling of oral health behaviour and the association between
      parental support and oral health, there has been no investigation of the home
      environment and its effect on oral health behaviour. The current study examines
      variables related to the family, including mealtime routines and family
      relationships to determine the best predictors of adolescent toothbrushing.
      METHODS: Data from the 2006 Health Behaviour in School-Aged Children Survey were
      modelled using logistic univariate and multivariable modelling with outcome
      variable twice-a-day toothbrushing. RESULTS: Higher family socioeconomic and
      affluence were significantly associated with greater odds of toothbrushing twice
      a day or more. Family structure was also significantly associated with girls'
      toothbrushing. However, under the multivariable model, eating breakfast was found
      to be the best predictor of twice-a-day toothbrushing among boys and girls. The
      next best predictor of boys' toothbrushing was eating family meals and of girls'
      toothbrushing, never going to bed hungry, followed by family affluence for both
      boys and girls. Under the multivariable model, family structure was no longer
      significantly associated with girls' toothbrushing. CONCLUSIONS: The study shows
      that the family and home environment should play a central role in the promotion
      of oral health, through mealtime routines, incorporating a fair parenting style
      and developing open and positive family relationships. Not only are these
      strongly associated with twice a day toothbrushing but, unlike sociodemographic
      factors, they may be relatively easy to adopt.

PMID- 19845714
TI  - Quantification of betel quid chewing and cigarette smoking in oral cancer
      patients.
AB  - BACKGROUND: Betel quid chewing and cigarette smoking are two of the risk factors
      for some dental diseases as well as oral cavity cancer in Taiwan. The aim of the
      study was to quantify these factors in oral cavity cancer patients and compare
      the prevalence of these factors in patients and the general population. METHODS:
      A questionnaire was designed to evaluate betel quid chewing, cigarette smoking
      and alcohol drinking in 254 patients, who had squamous cell carcinoma of the oral
      cavity, and had received surgical excision at the Changhua Christian Hospital in
      Taiwan between 2005 and 2008. The results were compared with those of population
      of Taiwan, based on a nation-wide survey with sample of 26 744 people. RESULTS:
      We found that more than 80% of the male patients were both betel quid chewers and
      smokers. Few women in the survey practiced betel quid chewing, cigarette smoking
      or alcohol drinking. Chewers and smokers usually started the habits in their 20s.
      On average, a chewer patient consumed 12 508 betel quid pieces per year, for 23.3
      years before the diagnosis of oral cavity cancer, making the total amount of
      betel quid consumed nearly 310 000 pieces; and a smoker patient consumed 469
      packs per year, for 28.5 years before diagnosis, making the total number of about
      14 000 packs. Patients with both habits had the age at diagnosis 4 years earlier
      than the smoker-only patients, 5 years earlier than the chewer-only patients, and
      6 years earlier than those with neither. CONCLUSIONS: On average, it took two
      decades of betel quid chewing and cigarette smoking before oral cavity cancer
      diagnosis, making the life-time consumption of these substances an astonishing
      amount. Betel quid chewing and cigarette smoking patients are more likely to be
      diagnosed with oral cavity cancer at a younger age than those who have just one
      habit or none. Patients that smoke more are not only more likely to be diagnosed
      at a younger age, but also at an advanced stage.

PMID- 19845715
TI  - What statistical method should be used to evaluate risk factors associated with
      dmfs index? Evidence from the National Pathfinder Survey of 4-year-old Italian
      children.
AB  - BACKGROUND: Traditional approaches to the analysis of dmfs/DMFS count data pose
      analytical challenges, considering the increasing proportion of zeroes in the
      distribution. The aim of this paper was to predict the probability of 'caries
      free' subjects and the dependence of dmfs index on the influence of childhood
      sociodemographic factors, through the application of regression models. METHODS:
      Data were gathered as part of the National Pathfinder Survey of 4-year-old
      Italian children. Clinical data on caries disease (dmfs) and childhood
      sociodemographic factors were collected. The predicted probability for Poisson,
      negative binomial and zero-inflated models (Poisson and negative binomial) were
      estimated using STATA commands for count outcomes. The outcome variable in the
      regression models was the severity of the disease (dmfs index), while
      statistically significant variables on bivariate analysis were considered as
      covariates. RESULTS: Out of 5538 children, 4344 (78.44%) had a dmfs = 0. The mean
      dmfs index was 1.36 (range: 0-104). The statistical significance of the
      dispersion parameter (O = 141.6, P < 0.0001) showed the inappropriateness of the
      Poisson model when compared with the negative binomial model. Vuong's test
      indicated that the zero-inflated models (ZIP and ZINB) fitted the data
      significantly better than the others (P < 0.001). A significative likelihood
      ratio statistic indicates that the ZINB regression model fitted better than ZIP
      model (P < 0.0001). The father's educational level was significant in both parts
      of the ZINB regression model (P < 0.05), implying that the degree of caries
      experience increases in children whose fathers have a low level of education,
      while the excess of caries-free children decreases. Moreover, the increase of
      coefficients in the zero-inflated part of ZINB regression model implies that the
      excess of caries-free subjects increases with the later age of tooth eruption.
      The observed underestimation of the frequencies of zero dmfs counts by the
      Poisson model is a common result when a dual-group process is not taken into
      account. CONCLUSIONS: These regression models provide a useful approach to
      handling count outcomes as dmfs/DMFS index in caries epidemiology.

PMID- 19845716
TI  - Controversies in dermatologic drug therapy.

PMID- 19845717
TI  - Topical antibiotics: therapeutic value or ecologic mischief?
AB  - Based on antibiotic prescribing data from 2003, dermatologists account annually
      for 8-9 million prescriptions for oral antibiotics, and 3-4 million prescriptions
      for topical antibiotics. Overall, much of the emphasis on concerns related to
      emergence of clinically significant antibiotic-resistant bacterial strains
      focuses on use of systemic antibiotics, however, topical antibiotic use may also
      have potential implications. The following article discusses the perspectives of
      the authors related to the potential therapeutic benefits and ecologic
      implications ("ecologic mischief") of topical antibiotic therapy for specific
      indications encountered in ambulatory dermatology practice.

PMID- 19845718
TI  - Controversies in the management of the cutaneous T cell lymphomas.
AB  - The primary cutaneous T cell lymphomas (CTCL) encompass all malignancies of the T
      cell where the skin is the primary organ of involvement. The diagnosis of a CTCL
      variant can be detoured by a number of obstacles including the slow evolution of
      the disease into a classic clinical and pathologic pattern. A realistic goal of
      early stage treatment is to reduce the likelihood of progression to a more
      advanced stage, not to achieve a cure. No studies have adequately compared the
      different systemic agents in patients with advanced CTCL so the clinician is left
      to act in the best interest of the patient with what evidence is available. When
      using the systemic agents, a "start low and go slow" strategy may offer patients
      several advantages. Dermatologists are uniquely trained to diagnose and to manage
      all but the most advanced stage patients with CTCL.

PMID- 19845720
TI  - Long-term efficacy of biologics in the treatment of psoriasis: what do we really
      know?
AB  - Psoriasis is a chronic inflammatory condition that often requires life-long
      treatment. Conventional therapies have not fully met the needs of psoriatic
      patients, because of limited efficacy, adverse effects with cumulative use, and
      patient inconvenience. In the past decade, biologic immunotherapies have become
      accepted treatments for psoriasis as a result of perceived efficacy and safety on
      the part of patients and practitioners. However, most data on these medications
      come from relatively limited short-term trials. In this review, we will focus on
      the available long-term data on the efficacy of the biologic agents. We will
      emphasize the strengths and weakness of the available data of the biologic agents
      that are Food and Drug Administration (FDA)-approved for the treatment of
      moderate to severe psoriasis (alefacept, efalizumab,* etanercept, infliximab, and
      adalimumab), with the inclusion of a newer agent currently under FDA evaluation
      (ustekinumab).

PMID- 19845721
TI  - Clinical risk management of Stevens-Johnson syndrome/toxic epidermal necrolysis
      spectrum.
AB  - Clinical risk management concedes that risk is inherent to all health-care
      processes. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are rare but potentially life-threatening reactions to medications. Risk
      management should be considered prior to starting, during, and after therapy.
      Prior to starting therapy, risks that need to be assessed include any specific
      patient groups that may be at greater risk for the development of SJS/TEN. Gene
      testing is in place for Chinese and Thai patients who are going to be exposed to
      carbamazepine. During therapy, it is important to recognize SJS/TEN as a possible
      adverse drug reaction. Diagnostic criteria have changed, and more data exist on
      drugs with an increased risk. Although there is no standardized treatment for all
      patients with SJS/TEN, options that have been used include cyclosporine,
      corticosteroids, and intravenous immunoglobulin. Standards of care are usually
      defined locally, but new treatments, such as amniotic membrane support for ocular
      damage, may need to be considered. Good communication skills are needed to allow
      practitioners to show empathy and to provide disclosure. Risk management after a
      reaction includes skills in acknowledging bad outcomes or error; freedom to say
      "sorry" as defined by "apology laws," and knowing the rights provided by "Quality
      Assurance Conferences," where the information discussed is protected. In other
      words, the patient is best supported after an event like SJS/TEN if the
      practitioner is knowledgeable about optimal care standards and their legal rights
      and obligations.

PMID- 19845719
TI  - Is there truly a risk of lymphoma from biologic therapies?
AB  - The treatment of psoriasis has undergone a revolution with the advent of biologic
      therapies, including infliximab, etanercept, adalimumab, efalizumab, and
      alefacept. Biologics are generally safe and well tolerated. However, there has
      been concern over the risk of lymphoma with use of these agents because of their
      immunosuppressive properties. This review summarizes the current evidence in
      regards to lymphoma risk with biologic therapy obtained from case reports and
      case series, observational studies, clinical trials, and meta-analyses. The
      majority of data for T-cell inhibitors comes from case reports and relatively
      small, short-term clinical trials. In addition to published case reports and case
      series, TNF-alpha inhibitors have also been studied extensively in large cohort
      studies and meta-analyses of clinical trials derived primarily from the
      rheumatoid arthritis population. Current data are neither sufficient to
      completely rule out an increased risk of lymphoma associated with biologics, nor
      to firmly establish a causal relationship between biologics and lymphoma. Short-
      to intermediate-term treatment with biologics (e.g., up to 4 years) appears to be
      very safe with respect to lymphoma risk, especially with TNF-alpha inhibitors in
      which their potential risks appear to be well defined. Continued vigilance is
      warranted; however, in the appropriate patient, the risk-to-benefit profile of
      psoriasis treatment with respect to lymphoma risk appears highly favorable.

PMID- 19845722
TI  - Should dermatologists prescribe hormonal contraceptives for acne?
AB  - ABSTRACT One of the primary factors contributing to the development of acne
      vulgaris is excess sebum. Sebaceous glands and sebum excretion are regulated, at
      least in part, by androgen hormones. Acne treatments that block this androgen
      effect include spironolactone and combination oral contraceptives (COC). Three
      COC are now FDA approved to treat moderate acne. Dermatologists must become
      experts at prescribing these hormonal contraceptives. Likewise, it is vital to be
      aware of contraindications to hormonal contraceptive therapy. Proper patient
      selection relies on an appropriate medical history and an assessment of blood
      pressure. A pelvic exam and/or Papanicolaou smear are not required prior to
      initiating therapy with a COC. It is important to counsel patients about
      potential adverse effects of COC pills and to establish appropriate expectations
      concerning acne improvement.

PMID- 19845723
TI  - Can short courses of systemic corticosteroids truly cause osteonecrosis?
AB  - One of the most feared complications of long-term corticosteroid therapy is
      osteonecrosis (avascular necrosis, aseptic necrosis). There is, no doubt, a
      causal role for systemic corticosteroids inducing osteonecrosis with such chronic
      therapy. The controversy involves whether short-term (<1 month) courses of
      systemic corticosteroids can truly induce osteonecrosis. This article presents
      both the biologic basis and statistical support for why such short-term courses
      of systemic corticosteroids rarely, if ever, truly induce osteonecrosis. Data
      from two very large populations (renal transplantation and systemic lupus
      erythematosus) with overall increased risk for osteonecrosis are carefully
      examined in view of the aforementioned controversy.

PMID- 19845724
TI  - Pressure recovery explains doppler overestimation of invasive pressure gradient
      across segmental vascular stenosis.
AB  - AIMS: This investigation sought to discern the accuracy of Doppler predictions of
      pressure drops in stenotic jets mimicking aortic coarctation (AC) across a broad
      spectrum of conditions, using an in vitro nonpulsatile flow model. METHODS AND
      RESULTS: The model allowed for different AC diameter and length, different
      cardiac output, and different diameter of the aorta distal to the AC. For each
      study condition, pressure drops across a model of AC were measured both
      noninvasively using the simplified Bernoulli equation (SBE) and invasively using
      the instantaneous actual pressure gradient. We observed a good correlation of SBE
      predicted and actual pressure gradients (slope = 0.929; r = 0.907, P < 0.0001)
      when AC diameter was small and the diameter of the aorta distal to the AC was
      large. However, we observed various degrees of overestimation by Doppler when
      mild AC was simulated (P = 0.0003), or when the diameter of the aorta distal to
      the coarctation was reduced (P < 0.0001). Increased AC length was associated with
      underestimation of actual pressure gradient by Doppler when AC diameter was
      small. Accounting for pressure recovery and viscous losses reduced the
      discrepancies between Doppler-predicted and actual pressure gradients in all
      study conditions (slope = 0.964; r = 0.989, P < 0.0001). CONCLUSIONS: Caution
      should be used in applying the SBE to the noninvasive assessment of AC severity.
      Significant segmental stenosis is associated with significant underestimation of
      the actual pressure gradient because of viscous losses. A substantial
      overestimation of the actual pressure drop due to a pressure recovery effect may
      occur in mild AC, especially when the distal aorta is not dilated.

PMID- 19845725
TI  - Understanding relationships among multiple ecosystem services.
AB  - Ecosystem management that attempts to maximize the production of one ecosystem
      service often results in substantial declines in the provision of other ecosystem
      services. For this reason, recent studies have called for increased attention to
      development of a theoretical understanding behind the relationships among
      ecosystem services. Here, we review the literature on ecosystem services and
      propose a typology of relationships between ecosystem services based on the role
      of drivers and the interactions between services. We use this typology to develop
      three propositions to help drive ecological science towards a better
      understanding of the relationships among multiple ecosystem services. Research
      which aims to understand the relationships among multiple ecosystem services and
      the mechanisms behind these relationships will improve our ability to sustainably
      manage landscapes to provide multiple ecosystem services.

PMID- 19845726
TI  - Coupled predator-prey oscillations in a chaotic food web.
AB  - Coupling of several predator-prey oscillations can generate intriguing patterns
      of synchronization and chaos. Theory predicts that prey species will fluctuate in
      phase if predator-prey cycles are coupled through generalist predators, whereas
      they will fluctuate in anti-phase if predator-prey cycles are coupled through
      competition between prey species. Here, we investigate predator-prey oscillations
      in a long-term experiment with a marine plankton community. Wavelet analysis of
      the species fluctuations reveals two predator-prey cycles that fluctuate largely
      in anti-phase. The phase angles point at strong competition between the
      phytoplankton species, but relatively little prey overlap among the zooplankton
      species. This food web architecture is consistent with the size structure of the
      plankton community, and generates highly dynamic food webs. Continued
      alternations in species dominance enable coexistence of the prey species through
      a non-equilibrium 'killing-the-winner' mechanism, as the system shifts back and
      forth between the two predator-prey cycles in a chaotic fashion.

PMID- 19845727
TI  - A general framework for neutral models of community dynamics.
AB  - Neutral models of community dynamics are a powerful tool for ecological research,
      but their applications are currently limited to unrealistically simple types of
      dynamics and ignore much of the complexity that characterize natural ecosystems.
      Here, we present a new analytical framework for neutral models that unifies
      existing models of neutral communities and extends the applicability of existing
      models to a much wider spectrum of ecological phenomena. The new framework
      extends the concept of neutrality to fitness equivalence and in spite of its
      simplicity explains a wide spectrum of empirical patterns of species diversity
      including positive, negative and unimodal productivity-diversity relationships;
      gradual and highly delayed declines in species diversity with habitat loss; and
      positive and negative responses of species diversity to habitat heterogeneity.
      Surprisingly, the abundance distribution in all of these cases is given by the
      dispersal limited multinomial (DLM), the abundance distribution in Hubbell's zero
      sum model, showing DLM's robustness and demonstrating that it cannot be used to
      infer the underlying community dynamics. These results support the hypothesis
      that ecological communities are regulated by a limited set of fundamental
      mechanisms much simpler than could be expected from their immense complexity.

PMID- 19845728
TI  - An examination of amphibian sensitivity to environmental contaminants: are
      amphibians poor canaries?
AB  - Nearly two decades ago, the global biodiversity crisis was catapulted to the
      front pages of newspapers with the recognition of worldwide amphibian declines.
      Amphibians earned their appellation, 'canaries in a coal mine', because of
      apparent high sensitivity to human-mediated environmental change. The most
      frequently cited causes for high susceptibility include permeable skin, a dual
      aquatic-terrestrial life cycle and a relatively rudimentary immune system. While
      some researchers have questioned the basis for the canary assertion, there has
      been no systematic evaluation of amphibian sensitivity to environmental
      challenges relative to other taxa. Here, we apply a database representing
      thousands of toxicity tests to compare the responses of amphibians relative to
      that of other taxonomic groups. The use of standardized methods combined with
      large numbers of identical challenges enables a particularly powerful test of
      relative effect size. Overall, we found that amphibians only exhibit moderate
      relative responses to water-borne toxins. Our findings imply that, as far as
      chemical contaminants are concerned, amphibians are not particularly sensitive
      and might more aptly be described as 'miners in a coal mine'. To the extent that
      amphibian declines have been mediated by chemical contaminants, our findings
      suggest that population losses and extinctions may have already occurred in a
      variety of taxa much more sensitive than amphibians.

PMID- 19845731
TI  - The ketogenic diet in treatment of two adults with prolonged nonconvulsive status
      epilepticus.
AB  - Prolonged status epilepticus (SE) can be refractory to conventional
      interventions, with high rates of subsequent morbidity and mortality. A high fat,
      low protein, low carbohydrate ketogenic diet (KD) has been used successfully to
      treat intractable epilepsy. However, its possible role in prolonged SE has not
      been well described. We report successful use of the KD in two adult patients
      with prolonged nonconvulsive SE (NCSE) refractory to multiple other
      interventions. Our observations suggest induction of ketosis may be a novel
      strategy to safely and effectively treat status in adults even after weeks to
      months of refractory seizures. Although there are few data regarding the use of
      the ketogenic diet in the treatment of adult epilepsy syndromes, it may be an
      option for the treatment of adults with refractory, prolonged SE.

PMID- 19845729
TI  - Innate but not adaptive immune responses contribute to behavioral seizures
      following viral infection.
AB  - PURPOSE: To examine the role of innate immunity in a novel viral infection
      induced seizure model. METHODS: C57BL/6 mice, mouse strains deficient in
      interleukin (IL)-1RI, IL-6, tumor necrosis factor (TNF)-RI, or myeloid
      differentiation primary response gene 88 (MyD88), or transgenic mice (OT-I) were
      infected with Theiler's murine encephalomyelitis virus (TMEV) or were mock
      infected. Mice were followed for acute seizures. Tissues were examined for neuron
      loss, the presence of virus (viral RNA and antigen), perivascular cuffs,
      macrophages/microglia, and gliosis, and mRNA expression of IL-1, TNF-alpha, and
      IL-6. RESULTS: IL-1 does not play a major role in seizures, as IL-1RI- and MyD88
      deficient mice displayed a comparable seizure frequency relative to controls. In
      contrast, TNF-alpha and IL-6 appear to be important in the development of
      seizures, as only 10% and 15% of TNF-RI- and IL-6-deficient mice, respectively,
      showed signs of seizure activity. TNF-alpha and IL-6 mRNA levels also increased
      in mice with seizures. Inflammation (perivascular cuffs, macrophages/microglia,
      and gliosis) was greater in mice with seizures. OT-I mice (virus persists) had a
      seizure rate that was comparable to controls (no viral persistence), thereby
      discounting a role for TMEV-specific T cells in seizures. DISCUSSION: We have
      implicated the innate immune response to viral infection, specifically TNF-alpha
      and IL-6, and concomitant inflammatory changes in the brain as contributing to
      the development of acute seizures. This model is a potential infection-driven
      model of mesial temporal lobe epilepsy with hippocampal sclerosis.

PMID- 19845730
TI  - Value of electrical stimulation and high frequency oscillations (80-500 Hz) in
      identifying epileptogenic areas during intracranial EEG recordings.
AB  - PURPOSE: Electrical stimulation (ES) is used during intracranial
      electroencephalography (EEG) investigations to delineate epileptogenic areas and
      seizure-onset zones (SOZs) by provoking afterdischarges (ADs) or patients'
      typical seizure. High frequency oscillations (HFOs--ripples, 80-250 Hz; fast
      ripples, 250-500 Hz) are linked to seizure onset. This study investigates whether
      interictal HFOs are more frequent in areas with a low threshold to provoke ADs or
      seizures. METHODS: Intracranial EEG studies were filtered at 500 Hz and sampled
      at 2,000 Hz. HFOs were visually identified. Twenty patients underwent ES, with
      gradually increasing currents. Results were interpreted as agreeing or
      disagreeing with the intracranial study (clinical-EEG seizure onset defined the
      SOZ). Current thresholds provoking an AD or seizure were correlated with the rate
      of HFOs of each channel. RESULTS: ES provoked a seizure in 12 and ADs in 19
      patients. Sixteen patients showed an ES response inside the SOZ, and 10 had
      additional areas with ADs. The response was more specific for mesiotemporal than
      for neocortical channels. HFO rates were negatively correlated with thresholds
      for ES responses; especially in neocortical regions; areas with low threshold and
      high HFO rate were colocalized even outside the SOZ. DISCUSSION: Areas showing
      epileptic HFOs colocalize with those reacting to ES. HFOs may represent a
      pathologic correlate of regions showing an ES response; both phenomena suggest a
      more widespread epileptogenicity.

PMID- 19845732
TI  - Factors contributing to depression in patients with epilepsy.
AB  - We investigated factors contributing to depression in patients with epilepsy.
      Data were collected from 150 adult patients. Beck Depression Inventory (BDI),
      Beck Anxiety Inventory, Daily Hassles Scale, Epilepsy Self-Efficacy Scale, Social
      Support Scale, Stress Coping Style Checklist, and Quality of Life in Epilepsy
      Inventory 31 (QOLIE-31) were used. The mean BDI score was 13.4 [standard
      deviation (SD) 9.0]. Abnormal BDI scores were recorded in 93 patients. Six
      significant predictors of BDI were identified in a stepwise linear regression
      analysis: level of stress (p < 0.001), social support (p = 0.037), anxiety (p =
      0.001), self-efficacy (p < 0.001), employment status (p = 0.021), and age (p =
      0.042). Stress accounted for 38.8% of the variance in BDI score, social support
      accounted for 6.8%, anxiety accounted for 3.9%, and the remaining three variables
      accounted for an additional 5.2% of the variance (total explained variance =
      54.7%).

PMID- 19845733
TI  - Sequential intrarectal diazepam and intravenous levetiracetam in treating acute
      repetitive and prolonged seizures.
AB  - In this retrospective study of institutionalized patients with mental
      retardation, we present the efficacy and safety of sequential treatment with
      intrarectal diazepam (IRD) gel (Diastat) and intravenous levetiracetam (IVL) in
      comparison with either treatment alone for acute repetitive or prolonged seizures
      (ARPS). We defined ARPS as >or=3 seizures of any type within 1 h or a single
      seizure of any type lasting >or=3 min. Eighty-eight ARPS episodes were treated in
      25 patients (14 female, age 21-72 years), with mainly symptomatic generalized
      epilepsy. There were no adverse events directly attributable to the
      administration of IRD or IVL. Seizure recurrence within 4 h of treatment, the
      primary outcome measure, was significantly lower after combined sequential IRD +
      IVL treatment (3 of 36) compared to IRD alone (6 of 24, p = 0.048) or IVL alone
      (10 of 28, p = 0.039). There was no statistically significant difference between
      the individual IRD and IVL treatments (p = 0.604). The estimated odds ratio (OR)
      indicated that the risk of seizure recurrence was higher after IRD or IVL
      monotherapy compared to combined IRD + IVL treatment. Subsequent emergency room
      (ER) transfers following seizure recurrence were least likely after IVL treatment
      (10%) compared to combined IRD + IVL (67%) or IRD (83%) treatment. These findings
      suggest that although IRD or IVL monotherapy is efficacious, the combination is
      superior in controlling ARPS in this special group of institutionalized patients.
      In addition, we speculate that a more reliable onset of action after IVL
      treatment results in rapid seizure control and fewer ER transfers, despite
      seizure recurrence.

PMID- 19845734
TI  - A population-based study of risk of epilepsy after hospitalization for traumatic
      brain injury.
AB  - PURPOSE: This study was undertaken to determine the risk of developing
      posttraumatic epilepsy (PTE) within 3 years after discharge among a population
      based sample of older adolescents and adults hospitalized with traumatic brain
      injury (TBI) in South Carolina. It also identifies characteristics related to
      development of PTE within this population. METHODS: A stratified random sample of
      persons aged 15 and older with TBI was selected from the South Carolina
      nonfederal hospital discharge dataset for four consecutive years. Medical records
      of recruits were reviewed, and they participated in up to three yearly follow-up
      telephone interviews. RESULTS: The cumulative incidence of PTE in the first 3
      years after discharge, after adjusting for loss to follow-up, was 4.4 per 100
      persons over 3 years for hospitalized mild TBI, 7.6 for moderate, and 13.6 for
      severe. Those with severe TBI, posttraumatic seizures prior to discharge, and a
      history of depression were most at risk for PTE. This higher risk group also
      included persons with three or more chronic medical conditions at discharge.
      DISCUSSION: These results raise the possibility that although some of the
      characteristics related to development of PTE are nonmodifiable, other factors,
      such as depression, might be altered with intervention. Further research into
      factors associated with developing PTE could lead to risk-reducing treatments.

PMID- 19845735
TI  - Adenosine A1 receptor blockage mediates theophylline-associated seizures.
AB  - Theophylline-associated seizures (TAS) often progress to prolonged or treatment
      resistant convulsions. Theophylline is a nonselective adenosine receptor
      antagonist. Adenosine is an endogenous anticonvulsant that can terminate
      seizures. Fever and young age have been reported to be risk factors for TAS. To
      elucidate the mechanism of TAS, we investigated the effect of theophylline and
      adenosine receptor ligands on hyperthermia-induced seizures in juvenile rats. The
      treatment dose of theophylline or control saline was injected intraperitoneally 1
      h before hyperthermia-induced seizures. The seizure threshold in the theophylline
      group was significantly lower and seizure duration was significantly longer than
      those in the control group. The addition of a selective adenosine A(1) receptor
      agonist and an adenosine kinase inhibitor completely counteracted the effects of
      theophylline. Moreover, a selective A(1) antagonist caused a significantly longer
      seizure duration compared with the control. These findings suggest that blockage
      of the adenosine A(1) receptor is the main cause of TAS.

PMID- 19845736
TI  - Severe and disabling constipation: an adverse effect of pregabalin.
AB  - The incidence of constipation as an adverse effect of pregabalin has previously
      been reported as low, with all cases described as either mild or moderate. From
      the experience of a tertiary referral epilepsy hospital center, we report several
      cases of severe and disabling constipation after initiating pregabalin, and
      resolving only on drug withdrawal. Of 80 consecutive patients, six (7.5%)
      developed significant constipation within 1-2 weeks of commencing pregabalin.
      Constipation was the most frequent adverse effect that required pregabalin to be
      withdrawn (6.3% of patients). The severity of symptoms was dose dependent.
      Pregabalin can cause marked constipation in some patients, and can lead to
      multiple unnecessary investigations and procedures if the clinician is not aware
      of this entirely reversible side effect.

PMID- 19845737
TI  - Proton MRS may predict AED response in patients with TLE.
AB  - PURPOSE: To compare relative N-acetylaspartate (NAA) measurements in temporal
      lobe epilepsy (TLE) patients with good response to the first trial of
      antiepileptic drugs (AEDs) (an important prognostic factor) to TLE patients who
      failed the first AED monotherapy and required further AED trials with monotherapy
      or polytherapy. METHODS: We studied 25 consecutive TLE patients who responded to
      first AED (responders) and 21 who did not (failure-group), as well as 27
      controls. Patients were seen regularly in our Epilepsy Service and underwent
      electroencephalography (EEG) investigation, high-resolution magnetic resonance
      imaging (MRI), and single-voxel proton MR spectroscopy. Voxels were tailored to
      the medial temporal region on each side and involved the anterior hippocampus.
      RESULTS: Analysis of variance (ANOVA) demonstrated significant variation of
      NAA/creatine (NAA/Cr) values in both hippocampi, ipsilateral and contralateral to
      the EEG focus (p < 0.001 and p = 0.021) across the groups. Pairwise post hoc
      comparisons showed reduced NAA/Cr in both hippocampi of failure-group compared to
      controls (p < 0.001) and compared to responders (p < 0.05), but not between the
      controls and responders. Individual analyses showed NAA/Cr ratios lower than 2
      SDs (standard deviations) below the mean of controls in 9 of 21 patients (42.8%)
      in the failure-group (6 with unilateral and 3 with bilateral reduction) but in
      none of the responders. DISCUSSION: These results indicate that patients with TLE
      who respond well to the first AED have significantly less evidence of neuronal
      and axonal damage/dysfunction compared to those who are refractory to the first
      AED trial.

PMID- 19845738
TI  - The usefulness of olfactory bulb kindling as a model for evaluation of
      antiepileptics.
AB  - PURPOSE: The present study was undertaken to clarify the behavioral and
      electroencephalographic characteristics of olfactory bulb (OB) kindling in rats,
      in comparison with those of amygdala (AMG) kindling. In addition, the usefulness
      of OB kindling as a model to evaluate antiepileptics was studied. METHODS:
      Bipolar electrical stimulation was applied to the OB or AMG every day until
      generalized seizure was achieved. Antiepileptics (carbamazepine, sodium
      valproate, zonisamide, clobazam, and topiramate), which are used for complex
      partial epilepsy or secondary generalized epilepsy in clinical practice, were
      orally administrated to kindled rats. RESULTS: The afterdischarge (AD) threshold
      of OB kindling is not different from that of AMG kindling. OB-kindled rats showed
      more rapid development of the seizure stage and AD duration than AMG-kindled
      rats; however, fully kindled AD duration did not differ between groups. In AMG
      kindled rats, AD on day 1 was localized only at the stimulation site, whereas in
      OB-kindled rats, AD on day 1 was observed at not only the stimulation site (OB)
      but also in the frontal cortex, hippocampus, and AMG. All five antiepileptics
      significantly inhibited both the seizure stage and AD duration in OB-kindled
      rats. In addition, carbamazepine, zonisamide, and topiramate were more effective
      in suppressing OB-kindled seizures. Zonisamide was not effective at any dose
      tested in AMG-kindled rats. DISCUSSION: OB kindling can be used as a new valuable
      model to evaluate antiepileptic drugs, with the advantage of its rapid
      development and the efficacy of antiepileptics.

PMID- 19845740
TI  - Cardiovascular risk factors and collateral artery formation.
AB  - Arterial lumen narrowing and vascular occlusion is the actual cause of morbidity
      and mortality in atherosclerotic disease. Collateral artery formation
      (arteriogenesis) refers to an active remodelling of non-functional vascular
      anastomoses to functional collateral arteries, capable to bypass the site of
      obstruction and preserve the tissue that is jeopardized by ischaemia. Hemodynamic
      forces such as shear stress and wall stress play a pivotal role in collateral
      artery formation, accompanied by the expression of various cytokines and invasion
      of circulating leucocytes. Arteriogenesis hence represents an important
      compensatory mechanism for atherosclerotic vessel occlusion. As arteriogenesis
      mostly occurs when lumen narrowing by atherosclerotic plaques takes place,
      presence of cardiovascular risk factors (e.g. hypertension, hypercholesterolaemia
      and diabetes) is highly likely. Risk factors for atherosclerotic disease affect
      collateral artery growth directly and indirectly by altering hemodynamic forces
      or influencing cellular function and proliferation. Adequate collateralization
      varies significantly among atherosclerotic patients, some profit from the
      presence of extensive collateral networks, whereas others do not. Cardiovascular
      risk factors could increase the risk of adverse cardiovascular events in certain
      patients because of the reduced protection through an alternative vascular
      network. Likewise, drugs primarily thought to control cardiovascular risk factors
      might contribute or counteract collateral artery growth. This review summarizes
      current knowledge on the influence of cardiovascular risk factors and the effects
      of cardiovascular medication on the development of collateral vessels in
      experimental and clinical studies.

PMID- 19845741
TI  - Significance of quantitative measurement of heparin-induced platelet antibodies.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic immune
      mediated adverse drug reaction. Antigen and platelet activation assays are used
      for detection of antibodies. Quantitative results from platelet factor 4 (PF4)
      dependent immunoassays may lead to inter-laboratory standardization of
      measurements. OBJECTIVES: The aim was to modify a PF4-dependent immunoassay to
      measure PF4/heparin antibodies quantitatively. METHODS: Over five consecutive
      years, 1070 samples from thrombocytopenic, heparin-treated patients were analyzed
      by a PF4/heparin ELISA and the heparin-induced platelet activation assay (HIPA).
      Results of ELISA assay were expressed as arbitrary units per liter (AU/L).
      RESULTS: Precision of ELISA at the concentration of 50 AU/L was 3.6%. Of 1070
      samples, 117 were positive for antibodies by ELISA and/or HIPA assay. The higher
      the antibody concentration was, the higher was the proportion of HIPA positive
      cases (>140 AU/L, 100%, n = 26; 100-140 AU/L, 55%, n = 20; 50-99 AU/L, 38%, n =
      29; 30-49 AU/L, 17%, n = 36). CONCLUSIONS: The measurement of anti-PF4/heparin
      antibody concentration is a new parameter that may improve the diagnosis of HIT.
      All samples with extremely strong antibody concentration were positive also by
      HIPA. For accuracy, antibody concentrations must be in the linear range of the
      assay and an international standard is needed.

PMID- 19845739
TI  - EEG spike activity precedes epilepsy after kainate-induced status epilepticus.
AB  - PURPOSE: Chronic epilepsy frequently develops after brain injury, but prediction
      of which individual patient will develop spontaneous recurrent seizures (i.e.,
      epilepsy) is not currently possible. Here, we use continuous radiotelemetric
      electroencephalography (EEG) and video monitoring along with automated computer
      detection of EEG spikes and seizures to test the hypothesis that EEG spikes
      precede and are correlated with subsequent spontaneous recurrent seizures.
      METHODS: The presence and pattern of EEG spikes was studied during long recording
      epochs between the end of status epilepticus (SE) induced by three different
      doses of kainate and the onset of chronic epilepsy. RESULTS: The presence of
      spikes, and later spike clusters, over several days after SE before the first
      spontaneous seizure, was consistently associated with the development of chronic
      epilepsy. The rate of development of epilepsy (i.e., increase in seizure
      frequency) was strongly correlated with the frequency of EEG spikes and the
      cumulative number of EEG spikes after SE. CONCLUSIONS: The temporal features of
      EEG spikes (i.e., their presence, frequency, and pattern [clusters]) when
      analyzed over prolonged periods, may be a predictive biomarker for the
      development of chronic epilepsy after brain injury. Future clinical trials using
      prolonged EEG recordings may reveal the diagnostic utility of EEG spikes as
      predictors of subsequent epilepsy in brain-injured humans.

PMID- 19845742
TI  - Severe paraneoplastic pemphigus in a patient with follicular lymphoma.

PMID- 19845743
TI  - Treatment practices in adults with chronic immune thrombocytopenia - a European
      perspective.
AB  - Immune thrombocytopenia (ITP) is characterised by platelet destruction and
      impaired production leading to isolated thrombocytopenia. The aim of this study,
      comprising a retrospective longitudinal cohort study complemented by a Delphi
      panel of 35 physicians, was to describe standard treatment practices and treating
      physician's perception and preferences for available treatment options in chronic
      ITP. The medical records of 610 patients were reviewed over 12 months. Mean age
      at the start of the observational period was 54.6 yr, median platelet count 77 x
      10(9)/L with 41% of patients having symptoms of ITP. Treated patients (61%)
      received an average of 2.7 medications either for ITP or ITP treatment-related
      side effects. An array of products was used, but the most frequent were
      corticosteroids. Delphi panel physicians (45%) indicated the main goals for
      treatment were to increase platelet levels to at least 30 x 10(9)/L to prevent
      bleeding or haemorrhage. The majority (89%) indicated that personal experience
      influenced treatment choice. Most (>80%) rated splenectomy and high-dose
      corticosteroids as the most effective but were concerned about side effects, and
      many (75%) would like access to interventions with improved efficacy and safety.
      The study highlights the need for updated evidence-based treatment guidelines to
      assist physicians in patient treatment decisions and to realise improvements in
      patient outcomes. It also identified perceived shortcomings of existing therapies
      and the need to establish an evidence base for newer interventions that could
      potentially make lasting response to treatment with fewer adverse effects an
      achievable goal.

PMID- 19845745
TI  - Free insulin-like growth factor (IGF)-1 and IGF-binding proteins-2 and -3 in
      serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients.
AB  - BACKGROUND: The insulin-like growth factor-1 (IGF-1) signaling system is
      regulated by many factors which interact in regulating the bioavailability of IGF
      I. In this context, little information is available on free IGF-1, the bioactive
      form of IGF-1, in amyotrophic lateral sclerosis (ALS). METHODS: We investigated
      the endogenous expression of IGF-1, and two related binding proteins (IGF-binding
      proteins, IGFBP-2 and BP-3) in serum and cerebrospinal fluid (CSF) of 54 sporadic
      ALS (sALS) patients. Twenty-five healthy individuals and 25 with other
      neurological diseases (OND) were used as controls. Total and free IGF-1, and
      IGFBP-3 levels were detected by immunoradiometric assay (IRMA); IGFBP-2 levels
      were determined by radioimmunoassay (RIA). RESULTS: Total and free IGF-1, IGFBP-2
      and BP-3 serum levels were not significantly different between patients and
      controls, although in sALS patients free IGF-1 was negatively correlated with ALS
      Functional Rating Scale-revised (ALS-FRS-R) score (r = -0.4; P = 0.046) and
      forced vital capacity (FVC) (r = -0.55; P < 0.04). In CSF, free IGF-1 was
      significantly increased in sALS patients compared with OND (P < 0.0001).
      CONCLUSIONS: Though in the serum we did not find significant differences amongst
      the three groups, IGF-1 bioavailability, represented by the free IGF-1 levels,
      correlated with disease severity. In the CSF, the significant increment of the
      free fraction of IGF-1 suggests an up-regulation of the IGF-1 system in the
      intrathecal compartment of sALS patients. Since IGF-1 is a trophic factor for
      different tissues, we speculate that high levels of the free IGF-1 in sALS might
      reflect a physiological defensive mechanism promoted in response to neural
      degeneration and/or muscle atrophy.

PMID- 19845746
TI  - Analysis of the GIGYF2 gene in familial and sporadic Parkinson disease in the
      Spanish population.
AB  - BACKGROUND AND PURPOSE: Linkage analysis in familial Parkinson's disease (PD)
      identified a locus in 2q36-37 (PARK11). Sequencing of GIGYF2 identified several
      variants only present amongst PD individuals. METHODS: We analyzed the presence
      of disease-associated GIGYF2 variants in familial and sporadic PD from Spanish
      origin by sequencing of 147 PD individuals. The entire GIGYF2 coding sequence was
      analyzed in 122 familial PD individuals and exons 2, 4, 8-11, 14 and 25-26 were
      sequenced in 25 sporadic PD to identify disease-associated variants. RESULTS: We
      found no variants associated with PD and failed to identify any of previously PD
      associated GIGYF2 variants in our sample. We identified four novel missense
      changes in GIGYF2. p.Met48Ile was found in a PD individual who also was a carrier
      of two PARKIN mutations. p.Q1244_Q1247del variant was present only in one PD
      individual but not found in 70 controls. However, its location in the highly
      polymorphic GIGYF2 glutamine/proline-rich region does not support a role in PD.
      Two variants (p.P1238insAGC and p.Q1249del) were present both in PD subjects and
      in controls. Additionally, the p.L1230_Q1237del variant, which was previously
      considered as a PD-associated change, was found in one control. CONCLUSION: Our
      findings suggest that GIGYF2 mutations are not a frequent cause of PD in the
      Spanish population, since we found no clearly segregating variants. We propose
      further analyses in PD subjects from different populations to define the role of
      GIGYF2. A clear pathogenic mutation in other gene at 2q36-37 in the PARK11-linked
      PD families would definitively disprove GIGYF2 as the responsible gene.

PMID- 19845747
TI  - Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results
      from the LADIS study.
AB  - BACKGROUND AND PURPOSE: White matter lesions (WMLs) caused by small vessel
      disease are common in elderly people and contribute to cognitive impairment.
      There are no established biochemical markers for WMLs. We aimed to study the
      relation between degree of WMLs rated on magnetic resonance imaging of the brain
      and cerebrospinal fluid (CSF) levels of structural biomarkers associated with
      Alzheimer's disease (AD) and subcortical vascular dementia. METHODS: Fifty-three
      non-demented elderly individuals with WMLs were subjected to lumbar puncture.
      Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs
      was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments
      of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total
      tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein
      (NFL), sulfatide and CSF/Serum-albumin ratio. RESULTS: Fifteen subjects had mild,
      23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between
      the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P <
      0.001). CSF sulfatide concentration displayed similar changes but less strongly.
      T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin
      ratio did not differ significantly between the groups. CONCLUSIONS: The
      association of increased CSF-NFL levels with increasing severity of WMLs in non
      demented subjects suggests that NFL is a marker for axonal damage in response to
      small vessel disease in the brain. This manifestation may be distinct from or
      earlier than the neurodegenerative process seen in AD, as reflected by the lack
      of association between WMLs and AD biomarkers.

PMID- 19845748
TI  - Another connection between essential tremor and Parkinson's disease?

PMID- 19845749
TI  - Growth hormone and ghrelin secretion are associated with clinical severity in
      Huntington's disease.
AB  - BACKGROUND AND PURPOSE: Huntington's disease (HD) is a fatal hereditary
      neurodegenerative disorder caused by an increased CAG repeat size in the
      huntingtin gene. Apart from neurological impairment, the disease is also
      accompanied by progressive weight loss, abnormalities in glucose homeostasis and
      a higher prevalence of diabetes mellitus, which may partly be caused by disturbed
      growth hormone (GH) and ghrelin secretion. Therefore, we aimed to perform a
      detailed analysis of GH and ghrelin secretion in HD patients in relation to
      clinical signs and symptoms. METHODS: In nine early-stage, medication-free HD
      patients and nine age-, gender- and body mass index-matched controls, we measured
      serum GH levels every 10 min for 24 h and assessed ghrelin response to food
      intake. Multi-parameter auto-deconvolution and approximate entropy analysis were
      applied to quantify basal, pulsatile, and total GH secretion rates as well as the
      regularity of GH secretion. RESULTS: We found no significant differences in GH
      and ghrelin secretion characteristics between HD patients and controls (total GH
      secretion: 137 +/- 36 vs. 181 +/- 43 mU/l/24 h, respectively; P = 0.439).
      However, in HD patients, both GH secretion and its irregularity as well as the
      degree of postprandial ghrelin suppression significantly increased with worsening
      motor and functional impairment (all P < 0.05). Moreover, postprandial ghrelin
      suppression also increased with decreasing body weight and higher CAG repeat
      number (both P < 0.05). CONCLUSIONS: These findings suggest changes in the
      regulation of GH and ghrelin secretion dynamics in early stage HD patients that
      could become more prominent in the later stages of the disease.

PMID- 19845751
TI  - Brain natriuretic peptide as a predictor of delayed atrial fibrillation after
      ischaemic stroke and transient ischaemic attack.
AB  - BACKGROUND AND PURPOSE: We investigated whether the brain natriuretic peptide
      (BNP) level can serve as a predictive biological marker of delayed atrial
      fibrillation (AF). METHODS: Two hundred and thirty seven consecutive patients
      admitted to our institution with acute ischaemic stroke or transient ischaemic
      attack (TIA) within 24 h of onset were enrolled. The patients were classified
      according to the presence or absence of AF upon admission [AF and sinus rhythm
      (SR) groups]. The SR group was subdivided based on the development of AF after
      admission (new- and non-AF groups). We compared the characteristics between the
      AF and SR groups, and between the new- and non-AF groups. The factors associated
      with new-AF were investigated by multivariate logistic regression analysis.
      RESULTS: Amongst the enrolled patients, 72 (30.4%) had AF upon admission (AF
      group), and 13 (5.5%) developed AF thereafter (new-AF group). The plasma BNP
      level was significantly higher in the AF, than in the SR group (401.7 vs. 92.1
      pg/ml, P < 0.001). Moreover, the plasma BNP level was significantly higher in the
      new-, than in the non-AF group (184.7 vs. 84.1 pg/ml, P < 0.001). The optimal
      cutoff BNP level required to distinguish new-, from non-AF groups was 85.0 pg/ml,
      and the sensitivity and specificity was 83.3% and 76.2%, respectively. On
      multivariate logistic regression analysis, plasma BNP level >85.0 pg/ml (odds
      ratio, 7.20; 95% confidence interval, 1.71 to 30.43, P = 0.007) was an
      independent factor associated with new-AF. CONCLUSION: High plasma BNP level
      should be a strong predictor of delayed AF after ischaemic stroke or TIA.

PMID- 19845752
TI  - Immune therapy for chronic inflammatory demyelinating polyneuropathy: from
      clinical trials to real-life.

PMID- 19845753
TI  - About the cutaneous targets of bexarotene in CTCL patients.
AB  - There are several approved therapies for cutaneous T-cell lymphoma (CTCL). The
      retinoids are one of the major biologic response modifiers used in CTCL,
      producing good response rates but few complete responses. Bexarotene has been
      demonstrated to act on malignant T-cells by inducing their apoptosis, but nothing
      is known about its role on keratinocytes and Langerhans cells.
      Immunohistochemical analysis using CD1a, HLA-DR, ICAM-1 (activation markers),
      CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene
      exposed cutaneous explants and skin biopsy specimens from patients treated with
      bexarotene. None of the studied markers was significantly modulated both on
      cutaneous explants and on skin biopsy specimens after treatment with bexarotene,
      compared to controls. Langerhans cells and keratinocytes do not appear to play a
      central role in the therapeutic control of CTCL by bexarotene therapy. The main
      bexarotene's target thus remains T-cells by inducing their apoptosis, a mechanism
      that is different from the other retinoids used in CTCL.

PMID- 19845754
TI  - Effect of honey and its major royal jelly protein 1 on cytokine and MMP-9 mRNA
      transcripts in human keratinocytes.
AB  - Honey has been used since ancient times as a remedy in wound healing. However,
      even though the results from randomized clinical trials document that honey
      accelerates wound healing, no study dealing with its influence on human skin
      cells (epidermal keratinocytes and dermal fibroblast) has been performed. We
      demonstrate that keratinocytes, which are known to be involved in wound healing,
      are responsible for elevated production of mediators including cytokines (TNF
      alpha, IL-1beta and TGF-beta) and matrix metalloproteinase-9 (MMP-9) after
      incubation with honey. Real-time PCR was performed for the quantification of mRNA
      level of selected cytokines and MMP-9. Furthermore, we show that the increased
      level of MMP-9 in the epidermis following incubation with honey leads to
      degradation of type IV collagen in the basement membrane. These data indisputably
      demonstrate that honey activates keratinocytes and support the findings that
      honey may accelerate wound healing process.

PMID- 19845755
TI  - Absence of modulation of CD4+CD25 regulatory T cells in CTCL patients treated
      with bexarotene.
AB  - Cutaneous T-cell lymphoma (CTCL) are a heterogeneous group of lymphoproliferative
      disorders, characterized by the infiltration of the epidermis by mature and
      activated malignant CD4+ T-lymphocytes. Retinoids such as retinoic acid and
      synthetic analogues have long been used alone or in combination with other
      therapies for CTCL. Bexarotene, the first synthetic highly selective RXR
      retinoid, was approved for the treatment of all stages of CTCL in patients
      refractory to at least one systemic therapy. Recently, six cases in which the
      initiation of bexarotene therapy for CTCL was associated with the progression of
      internal disease despite improvement of cutaneous signs and symptoms were
      reported. Moreover, it has been established that retinoids promote the generation
      of CD4+ Foxp3+ regulatory T cells, raising the question of an induction of
      regulatory T-cells by bexarotene. The aim of this work was to determine if
      bexarotene induces an increase of functional regulatory T cells which could play
      a role in the development of secondary extra-cutaneous lymphomas. Regulatory T
      cells were studied both in cutaneous biopsy specimens using an
      immunohistochemical analysis of CD4, CD25 and Foxp3 and in blood where proportion
      and functionality of circulating CD4+CD25(high) T-cells were determined. The
      study was performed in 10 patients [five patients with Sezary syndrome (SS) and
      five mycosis fungoides (MF)], treated for 6 months with bexarotene. Four healthy
      donors were used as controls for phenotypic and functional analysis on PBL. We
      found that the frequency of CD4+CD25(high) Treg cells was not significantly
      different before starting bexarotene and after 6 months of treatment in CTCL
      patients. However, we observed that the frequency of CD4+CD25(high) Treg cells
      before the beginning of the treatment was significantly increased compared to
      healthy donors. In addition, functional assays demonstrated that Foxp3 expressing
      CD4+CD25(high) T-cells were capable of suppressing autologous CD4 + CD25- T-cell
      proliferation. In the present work, we detected the presence of functional
      circulating CD4+CD25(high) Foxp3+ regulatory T-cells in CTCL patients, with an
      increased frequency compared to healthy donors. The treatment with bexarotene
      does not seem to affect the regulatory T-cell compartment.

PMID- 19845756
TI  - Probing tumor and peritumoral tissues in superficial and nodular basal cell
      carcinoma using polarized Raman microspectroscopy.
AB  - Basal cell carcinoma (BCC) can sometimes lead, through a possible invasion of the
      dermis and the subcutaneous tissue, to serious local damage to the patient.
      Several histological types of BCC are reported, among them, the superficial,
      nodular and infiltrative forms. This study reports the use of polarized Raman
      microspectroscopy on the nodular and superficial types to discriminate between
      healthy epidermis and tumor, and between normal and peritumoral stroma. This
      technique probes additional information than conventional Raman spectroscopy
      because it is sensitive to the molecular ordering of tissue components.
      Depolarization ratios and hierarchical cluster analysis demonstrate that
      polarized Raman microspectroscopy can better identify the tumor and the
      peritumoral dermis than conventional Raman microspectroscopy, and hence gives
      potential complementary data about their molecular characteristics (molecular
      composition, secondary structure of proteins, intra- and/or inter-molecular
      bonding). Our findings also show that although superficial and nodular types of
      BCC were analysed, clear differences between the spectra of peritumoral and
      normal dermis could be detected.

PMID- 19845757
TI  - Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma.
AB  - Nestin is an intermediate filament expressed in proliferating neural progenitor
      cells and has been considered as a stem cell marker. Nestin is also found in
      melanoma and we recently demonstrated that its expression in melanoma cell lines
      is regulated by the transcription factors SOX9 and SOX10, but not BRN2. In this
      study, the expression levels of nestin, BRN2, SOX9 and SOX10 were analysed in
      tissues of melanoma (n = 78) and melanocytic nevi (n = 26) by
      immunohistochemistry. All proteins were highly expressed in primary and
      metastatic melanomas and, apart from BRN2, showed much lower levels in
      melanocytic nevi. Significant coexpression of nestin with SOX9 and SOX10 was
      found in primary melanoma confirming our in vitro data. Correlation analysis with
      clinicopathological data revealed that nestin was significantly associated with
      presence of ulceration in primary tumors and SOX9 with more advanced stage of
      disease. Our data reveal that SOX9 and SOX10 are highly expressed in melanoma and
      seem to have a regulatory role in nestin expression. The association with
      ulceration and advanced-stage tumors, respectively, suggests that nestin and SOX9
      may be negative prognostic markers in melanoma.

PMID- 19845758
TI  - The NF-kappaB signalling pathway is involved in the LPS/IL-2-induced upregulation
      of FoxP3 expression in human CD4+CD25high regulatory T cells.
AB  - Regulatory T cells (Treg) have been found to be central for host defense
      regulation against microbial antigens, the prevention of allergic and autoimmune
      diseases and the suppression of effective tumor immune responses. However, the
      influence of the microenvironment and the mechanisms leading to their activation
      in the periphery still remain unclear. In vitro infection models revealed that
      survival and suppressive function of Treg is improved when they are confronted
      with lipopolysaccharide (LPS). Because LPS initiates signalling via the receptor
      Toll-like receptor 4 (TLR4) and the consequent activation of the transcription
      factor nuclear factor-kappaB (NF-kappaB), we investigated TLR4 expression and NF
      kappaB regulation in human Treg. We demonstrated that LPS in combination with IL
      2 induces human CD25(+)FoxP3(+) T cells in vitro. FoxP3 expression of purified
      natural Treg increased and suppressive capacity was markedly improved compared
      with unstimulated Treg upon stimulation with LPS/IL-2. Furthermore, blockade of
      the NF-kappaB pathway by a selective inhibitor of IkappaB kinase (IKK)beta
      abrogated the upregulation of FoxP3 expression. Taken together, our results
      suggest an important role of the NF-kappaB signalling pathway for the induction
      and modulation of suppressive function of natural Treg, if they are confronted
      with TLR4-stimulating agents such as Gram-negative bacteria.

PMID- 19845760
TI  - Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid
      nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin
      model.
AB  - An ex vivo porcine skin model was utilized to analyse the penetration of 5
      aminolevulinic acid (5-ALA) contained in a nanoemulsion-based formulation BF-200
      ALA (10% 5-ALA-hydrochloride) versus 16% aminolevulinate methyl ester
      hydrochloride in a commercially cream (MAL cream) by fluorescence microscopy of
      their common metabolite protoporphyrin IX (PpIX) after 3, 5, 8 and 12 h.
      Fluorescence signals of PpIX in pig skin treated with BF-200 ALA were stronger
      than those for MAL cream. At 8 and 12 h, the PpIX fluorescence signals were 4.8-
      and 5.0-fold higher than those measured after MAL cream application. Fluorescence
      signals of PpIX after application of BF-200 ALA were detected in deeper tissue
      layers of the epidermis than after application of MAL cream (97.2 +/- 5.7 microm
      for BF-200 ALA vs 42.0 +/- 4.2 microm for MAL cream). These data implicate that
      BF-200 ALA in photodynamic therapy might lead to a superior therapeutically
      effect of intraepidermal (in situ) squamous cell carcinomas.

PMID- 19845761
TI  - Lipidome of narrow-band ultraviolet B irradiated keratinocytes shows apoptotic
      hallmarks.
AB  - BACKGROUND: UV light triggers a variety of biological responses in irradiated
      keratinocytes that might be associated with global perturbation of their
      lipidome. However, lipids that are specifically affected and the exact molecular
      mechanisms involved remain poorly understood. OBJECTIVES: To characterize time
      dependent changes of the lipidome of cultured keratinocytes induced by narrow
      band ultraviolet B (NB-UVB) irradiation. METHODS: Immortalized human
      keratinocytes (HaCaT) were cultured under standard conditions, irradiated with NB
      UVB light (311 nm) at 400 and 800 mJ/cm(2) and collected 1, 2, 3, 6, 12 and 24 h
      later for lipid extraction. Lipid extracts were separated on silica plates in
      chloroform/ethanol/water/triethylamine (35:40:9:35) and in n-hexane/ethylacetate
      (5:1) followed by quantitative shotgun lipidomics analysis. RESULTS: Irradiation
      with 800 mJ/cm(2) of NB-UVB altered morphology and lipidome composition of HaCaT
      cells. Ceramide content increased two-fold 6- and 12-h postirradiation with 800
      mJ/cm(2), followed by threefold increase in triacylglycerols (TAGs) that peaked
      at 24 h. In addition, we observed marked increase of various phosphatidylcholine
      and phosphatidylethanolamine ethers, whereas phosphatidylcholine-species with
      short-chain fatty acid moieties decreased. The abundance of other lipid species
      was altered to lesser extent or remained unchanged. CONCLUSIONS: NB-UVB affected
      the cellular lipidome of keratinocytes in strictly apoptosis-specific manner.

PMID- 19845762
TI  - Complementary medicinal chemistry-driven strategies toward new antitrypanosomal
      and antileishmanial lead drug candidates.
AB  - Trypanosomiases and Leishmaniases are neglected tropical diseases that affect the
      less developed countries. For this reason, they did not and still do not have
      high visibility in Western societies. The name neglected diseases also refers to
      the fact that they often received little interest at the level of public
      investment, research and development. The drug discovery scenario, however, is
      changing dramatically. After a period in which different socioeconomic factors
      have prevented massive research efforts in this field, such efforts have
      increased considerably in the very recent years, with significant scientific
      advancements. In this context, we have embarked on a new drug discovery project
      devoted to identification of new small molecules for the treatment of
      trypanosomal and leishmanial diseases. Two complementary approaches have been
      pursued and are reported here. The first deals with a structure-based drug
      design, and a privileged structure-guided synthesis of quinazoline compounds able
      to modulate trypanothione reductase activity was accomplished. In the second, a
      combinatorial library, built on a natural product-based strategy, was
      synthesized. Using whole parasite assays, different quinones have been identified
      as promising lead compounds. A combination of both approaches to hopefully
      overcome some of the challenges of anti-trypanosomatid drug discovery has
      eventually been proposed.

PMID- 19845763
TI  - Antibiofilm activity of coral-associated bacteria against different clinical M
      serotypes of Streptococcus pyogenes.
AB  - Streptococcus pyogenes is the frequent cause of purulent infections in humans.
      Formation of a biofilm is one of the important aspects of its pathogenicity.
      Streptococcus pyogenes biofilm communities tend to exhibit significant tolerance
      to antimicrobial challenge during infections. Exploring novel targets against
      biofilm-forming pathogens is therefore an important alternative treatment
      measure. We attempted to screen marine bacteria, especially coral-associated
      bacteria (CAB), for antibiofilm activity against streptococcal biofilm formation.
      The bacterial biofilms were quantified by crystal violet staining. Of 43 CAB
      isolates, nine clearly demonstrated antibiofilm activity. At biofilm inhibitory
      concentrations (BIC), biofilm formation was reduced up to 80%, and sub-BIC (0.5
      and 0.25 BIC) significantly reduced biofilm formation by up to 60% and 40-60%,
      respectively. Extracts of Bacillus horikoshii (E6) displayed efficient
      antibiofilm activity. As quorum sensing (QS) and cell surface hydrophobicity
      (CSH) are crucial factors for biofilm formation in S. pyogenes, the CAB were
      further screened for QS inhibition properties and CSH reduction properties. This
      study reveals the antibiofilm and QS inhibition property of CAB.

PMID- 19845764
TI  - Microbial diversity and activity are increased by compost amendment of metal
      contaminated soil.
AB  - Unlike organic pollutants, heavy metals cannot be degraded and can constitute a
      persistent environmental hazard. Here, we investigated the success of different
      remediation strategies in promoting microbial diversity and function with depth
      in an acidic soil heavily contaminated with Cu, Pb and Zn. Remediation involved
      the incorporation of either a high- or a low-quality compost or inorganic
      fertilizer into the topsoil and monitoring of microbial activity and diversity
      with soil depth over a 4-month period. While changes in topsoil microbial
      activity were expected, the possible effects on the subsurface microbial
      community due to the downward movement of metals, nutrients and/or soluble
      organic matter have not been examined previously. The results showed that both
      compost additions, especially the low-quality compost, resulted in significantly
      increased bacterial and fungal diversity (as assessed by terminal restriction
      fragment length polymorphism) and activity compared with the inorganic and
      control treatments in the topsoil. Although phospholipid fatty acid profiling
      indicated that compost addition had promoted enhanced microbial diversity in the
      subsoil, no concomitant increase in subsoil microbial activity was observed,
      suggesting that amelioration of the heavy metals remained localized in the
      topsoil. We conclude that although composts can successfully immobilize heavy
      metals and promote ecosystem diversity/function, surface incorporation had little
      remedial effect below the surface layer over the course of our short-term trial.

PMID- 19845765
TI  - Disruption of cagA, the apoprotein gene of chromoprotein antibiotic C-1027,
      eliminates holo-antibiotic production, but not the cytotoxic chromophore.
AB  - C-1027 is a chromoprotein of the nine-membered enediyne antitumour antibiotic
      family, comprising apoprotein to stabilize and transport the enediyne
      chromophore. The disruption of apoprotein gene cagA within the C-1027
      biosynthetic gene cluster abolished C-1027 holo-antibiotic production detected by
      an antibacterial assay, as well as the expression of the apoprotein and C-1027
      chromophore extracted following protein precipitation of the culture supernatant.
      Complementation of the cagA-disrupted mutant AKO with the intact cagA gene
      restored C-1027 production, suggesting that cagA is indispensable for holo
      antibiotic production. Overexpression of cagA in the wild-type strain resulted in
      a significant increase in C-1027 production as expected. Surprisingly,
      electrospray ionization (ESI)-MS and ESI-MS/MS analyses suggested that the AKO
      mutant still produced the C-1027 enediyne chromophore [m/z=844 (M+H)(+)] and its
      aromatized product [m/z=846 (M+H)(+)]. Consistent with this, the results from
      gene expression analysis using real-time reverse transcriptase-PCR showed that
      transcripts of the positive regulator sgcR3 and the structural genes sgcA1,
      sgcC4, sgcD6 and sgcE were readily detected in the AKO mutant as well as in the
      wild-type and the complementation strain. These results provided, for the first
      time, evidence suggesting that the apoprotein of C-1027 is not essential in the
      self-resistance mechanism for the enediyne chromophore.

PMID- 19845766
TI  - Reduced elimination clearance of micafungin in rats with cholestatic
      hyperbilirubinemia.
AB  - We examined whether the pharmacokinetic disposition of micafungin (MCFG), an
      echinocandin class antifungal agent, is altered in hyperbilirubinemia using a rat
      model prepared by bile duct ligation (BDL). Serum bilirubin levels were increased
      depending upon the duration of BDL. The elimination rate constant and total body
      clearance (CL(tot)) of MCFG were reduced by 24% and 16%, respectively, after BDL
      for 1 h, but there was no significant change in the apparent volume of
      distribution at steady-state. The degree of reduction in the CL(tot) was much
      greater 7 days after BDL as compared with that 1 h after BDL (44% vs. 16%).
      However, the proportion of the biliary clearance in the CL(tot) was about 10%.
      This is similar to the extent of decrease in the CL(tot) by occlusion of the bile
      duct, demonstrating that decreased biliary excretion of MCFG makes only a minor
      contribution to its pharmacokinetic change. These findings suggest that the
      metabolic capacity of MCFG is markedly impaired in hepatic hypofunction secondary
      to hyperbilirubinemia, providing a fundamental explanation for the previous
      clinical report that there is a significant correlation between dose-adjusted
      plasma MCFG concentration and serum bilirubin levels.

PMID- 19845767
TI  - Anti-arthritic effect of scopoletin, a coumarin compound occurring in Erycibe
      obtusifolia Benth stems, is associated with decreased angiogenesis in synovium.
AB  - Scopoletin is the main constituent of coumarin found in the stems of Erycibe
      obtusifolia Benth, a traditional Chinese medicine used in the treatment of
      rheumatoid arthritis. We have previously demonstrated that scopoletin is able to
      decrease the serum level of uric acid in hyperuricemic mice induced by potassium
      oxonate, and attenuate croton oil-induced inflammation. In the present study, we
      evaluated the anti-arthritic effects of scopoletin in rat adjuvant-induced
      arthritis by assessing paw swelling, pathology, and synovial angiogenesis. It was
      found that scopoletin, injected intraperitoneally at doses of 50, 100 mg/kg,
      reduced both inoculated and non-inoculated paw swelling as well as articular
      index scores, and elevated the mean body weight of adjuvant-induced arthritic
      rats. Rats treated with higher dose of scopoletin showed a near-normal
      histological architecture of the joints and a reduced new blood vessel formation
      in the synovial tissues. Furthermore, scopoletin downregulated the overexpression
      of vascular endothelial growth factor, basic fibroblast growth factor and
      interleukin 6 in the synovial tissues of adjuvant-induced arthritic rats. In
      conclusion, scopoletin is capable of ameliorating clinical symptoms of rat
      adjuvant-induced arthritis, by reducing numbers of new blood vessels in the
      synovium and the production of important endogenous angiogenic inducers.
      Therefore, this compound may be a potential agent for angiogenesis-related
      diseases and could serve as a structural base for screening more potent synthetic
      analogs.

PMID- 19845768
TI  - Perception of risk of adverse drug reactions: a 3-year follow-up of a cohort of
      medical students.
AB  - Previous studies have pointed out the question of effective training and
      information to health professionals on pharmacovigilance. The lack of training is
      known to induce inadequate use of drugs and noncompliance of patients.
      Pharmacology teaching is performed in the third year of medical studies at the
      Toulouse Faculty of Medicine. The aim of the study was to investigate the
      perception of risk of adverse drug reactions (ADRs) by medical students at the
      end of the one year pharmacology course and two years later, after clinical
      training period. Sixty-seven students were interviewed in May 2005 and in October
      2007. Visual analogue scales were used to define a score of perceived risk of
      ADRs associated with each drug class (ranking from 0 to 10) before and after
      pharmacology training. The drug classes evaluated were antibiotics,
      anticoagulants, antidepressants, aspirin, contraceptive pill, corticosteroids,
      drugs for arterial hypertension, drugs for diabetes (other than insulin),
      hypnotics, hypocholesterolaemic drugs, nonsteroidal anti-inflammatory drugs
      (NSAIDs), postmenopausal hormone replacement therapy and tranquilisers. After
      pharmacology courses (May 2005), antidepressants were ranked as the most
      dangerous drugs by medical students [median score (25th-75th centiles): 7.7 (6.3
      8.6)], followed by anticoagulants [7.6 (6.6-8.4)] and hypnotics [7.4 (6.1-8.1)].
      Contraceptive pills was listed in the last position [median score [4.7 (2.2
      6.7)]. Two years later (October 2007), anticoagulants moved into the first
      position [8.3 (7.3-9.2)], followed by NSAIDs [6.9 (5.0-8.4)] and aspirin [6.8
      (5.8-8.4)]. Contraceptive pills remained in the last position. No change was
      observed for NSAIDs and aspirin, still ranked as dangerous drugs by medical
      students after clinical training. Values of perceived risk were significantly
      increased for anticoagulant (+9.2%, P < 0.01) and hypoglycemiant drugs (+27.7%, P
      < 0.0001). The perceived risk significantly decreased for hypocholesterolaemic (
      14.3%, P < 0.0001) and antidepressant drugs (-19.5%, P < 0.0001), but not for
      hypnotics. The study shows that the perception of risk of ADRs by medical
      students was modified after clinical training. They were still aware of
      potentially serious ADRs associated with anticoagulants, aspirin or NSAIDs, but
      they remained less cautious for drugs such as antidepressants. Additional
      pharmacology training at the end of medical studies will be useful.

PMID- 19845769
TI  - The antinociceptive effect and adverse drug reactions of oxycodone in human
      experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes.
AB  - The aim of this study was to search for a possible association between the
      variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and
      C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and
      adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to
      experimental pain including electrical stimulation and the cold pressor test were
      included. A118G: We found that the variant G allele was associated with reduced
      antinociceptive effect as measured by pain tolerance thresholds to single
      electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P =
      0.007). C3435T: The carriers of the variant T allele generally had less adverse
      drug reactions on oxycodone than the carriers of the wild-type genotype.
      G2677T/A: The carriers of the variant T allele had a better antinociceptive
      effect of oxycodone than the carriers of the wild-type genotype in the cold
      pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25%
      reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug
      reactions. The combined wild-type genotype 3435CC-2677GG was associated with less
      antinociceptive effect of oxycodone in the discomfort rating of the cold pressor
      test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions
      than the carriers of the variant alleles. We found a moderate association between
      less antinociceptive effect of oxycodone and the variant allele of A118G. There
      was strong association between less adverse drug reactions of oxycodone and the
      variant alleles of C3435T and G2677T/A.

PMID- 19845770
TI  - A unique domain in RANK is required for Gab2 and PLCgamma2 binding to establish
      osteoclastogenic signals.
AB  - TRAF6 is essential for osteoclastogenesis and for both RANK- and CD40-mediated
      activation of IKK and MAPKs. RANK, but not CD40, can promote osteoclastogenesis
      because only RANK induces NFATc1 activation through PLCgamma2-induced Ca(2+)
      oscillations together with the co-stimulatory signals emanating from immune
      receptors linked to ITAM-containing adaptors. These previous data suggest that
      RANK harbors a unique domain that functions in concert with the TRAF6-binding
      site in osteoclastogenesis. Here we identify such a domain, highly conserved
      domain in RANK (HCR), which is dispensable for the early phase of RANK and ITAM
      signaling but is essential for their late-phase signaling, including sustained
      activation of NF-kappaB and PLCgamma2 leading to NFATc1 activation. HCR recruits
      an adaptor protein, Gab2, which further associates with PLCgamma2 in the late
      phase. Formation of the HCR-mediated signaling complex could account for the
      sustained activation of NF-kappaB and PLCgamma2. The present study identifies HCR
      as a unique domain that plays a critical role in the long-term linkage between
      RANK and ITAM signals, providing a molecular basis for therapeutic strategies.

PMID- 19845771
TI  - Dmap1 plays an essential role in the maintenance of genome integrity through the
      DNA repair process.
AB  - Faithful control of cell cycle checkpoint and DNA repair contributes to prevent
      the cells from chromosomal instability and tumorigenesis. Dnmt1-associated
      protein 1 (Dmap1), a component of the NuA4 histone acetyltransferase complex, was
      originally identified as an interacting molecule with DNMT1 which co-localizes
      with PCNA at DNA replication foci. However, its role in cellular functions
      remains largely unknown. Here we show that Dmap1 knockdown in mouse embryonic
      fibroblasts (MEFs) lead to spontaneous double-strand breaks (DSBs), resulting in
      growth arrest because of p53-dependent cell cycle checkpoint activation. Deletion
      of both Dmap1 and p53 in MEFs synergized towards enhanced generation of DSBs,
      chromosomal abnormalities and tumor development in mice. Notably, we found that,
      on DNA damage, Dmap1 was recruited to the damaged sites to form complexes with
      gamma-H2AX and replication factors, including Pcna. Depletion of Dmap1 in MEFs
      abrogated the stable accumulation of Pcna at the DNA damaged sites. Furthermore,
      the re-introduction of Dmap1 mutants with a reduced capacity to bind Pcna failed
      to ameliorate the impaired DNA repair in Dmap1-depleted cells. These findings
      indicate that Dmap1 is required to involve Pcna in DNA repair. Together, Dmap1
      plays a crucial role in DNA repair, and is indispensable for the maintenance of
      chromosomal integrity.

PMID- 19845772
TI  - Cost of care of haemophilia with inhibitors.
AB  - In Western countries, the treatment of patients with inhibitors is presently the
      most challenging and serious issue in haemophilia management, direct costs of
      clotting factor concentrates accounting for >98% of the highest economic burden
      absorbed for the healthcare of patients in this setting. Being designed to
      address questions of resource allocation and effectiveness, decision models are
      the golden standard to reliably assess the overall economic implications of
      haemophilia with inhibitors in terms of mortality, bleeding-related morbidity,
      and severity of arthropathy. However, presently, most data analyses stem from
      retrospective short-term evaluations, that only allow for the analysis of direct
      health costs. In the setting of chronic diseases, the cost-utility analysis, that
      takes into account the beneficial effects of a given treatment/healthcare
      intervention in terms of health-related quality of life, is likely to be the most
      appropriate approach. To calculate net benefits, the quality adjusted life year,
      that significantly reflects such health gain, has to be compared with specific
      economic impacts. Differences in data sources, in medical practice and/or in
      healthcare systems and costs, imply that most current pharmacoeconomic analyses
      are confined to a narrow healthcare payer perspective. Long-term/lifetime
      prospective or observational studies, devoted to a careful definition of when to
      start a treatment; of regimens (dose and type of product) to employ, and of
      inhibitor population (children/adults, low-responding/high responding inhibitors)
      to study, are thus urgently needed to allow for newer insights, based on reliable
      data sources into resource allocation, effectiveness and cost-utility analysis in
      the treatment of haemophiliacs with inhibitors.

PMID- 19845773
TI  - How we treat: patients with haemophilia undergoing screening colonoscopy.

PMID- 19845774
TI  - A study of reported factor VIII use around the world.
AB  - The effect of replacement therapy has significantly improved the morbidity and
      mortality of people with haemophilia A in high income countries, a recent socio
      economic development as the availability of safe concentrates has been matched by
      a willingness for their provision through reimbursement. In the developing world,
      however, this state has not been achieved, primarily because of the low
      visibility of haemophilia coupled with its expense, leading to inadequate
      treatment with its sequelae of severe pain, joint deformities, arthropathy,
      disabilities, and even death in childhood or early adult life. The objective of
      this paper was to study the reported factor VIII (FVIII) use on a country-by
      country basis. Data on the reported FVIII use for 104 countries were obtained
      from the Marketing Research Bureau, Inc. and the World Federation of Hemophilia.
      The results show that FVIII use varies considerably among countries, even among
      the wealthiest of countries. The use of FVIII concentrate increases as economic
      capacity increases; in addition, consumption of FVIII has been increasing at a
      greater rate in high income countries. Given these trends, there probably will be
      a global increase in FVIII concentrates usage. Such information is critical for
      national healthcare agencies to determine realistic budget priorities in planning
      for an increased allocation of resources required to improve the treatment of
      patients with haemophilia A. This information is also important for
      pharmaceutical manufacturers to adequately plan for increased production of FVIII
      concentrates.

PMID- 19845775
TI  - A study of variations in the reported haemophilia A prevalence around the world.
AB  - The objectives of this paper were to study the reported haemophilia A prevalence
      (per 100 000 males) on a country-by-country basis and address the following: Does
      the reported prevalence of haemophilia A vary by national economies? We collected
      prevalence data for 106 countries from the World Federation of Hemophilia (WFH)
      annual global surveys and the literature. We found that the reported haemophilia
      A prevalence varied considerably among countries, even among the wealthiest of
      countries. The prevalence (per 100 000 males) for high income countries was 12.8
      +/- 6.0 (mean +/- SD) whereas it was 6.6 +/- 4.8 for the rest of the world.
      Within a country, there was a strong trend of increasing prevalence over time-
      the prevalence for Canada ranged from 10.2 in 1989 to 14.2 in 2008 (R = 0.94 and
      P < 0.001) and for the United Kingdom it ranged from 9.3 in 1974 to 21.6 in 2006
      (R = 0.94 and P < 0.001). Prevalence data reported from the WFH compared well
      with prevalence data from the literature. Patient registries generally provided
      the highest quality of prevalence data. The lack of accurate country-specific
      prevalence data has constrained planning efforts for the treatment and care of
      people with haemophilia A. With improved information, healthcare agencies can
      assess budgetary needs to develop better diagnostic and treatment facilities for
      affected patients and families and work to ensure adequate supplies of factor
      VIII concentrates for treatment. In addition, this information can help
      manufacturers plan the production of concentrates and prevent future shortages.

PMID- 19845776
TI  - Effect of glycoPEGylation on factor VIIa binding and internalization.
AB  - SUMMARY: Recombinant coagulation factor VIIa (rFVIIa), which is widely used for
      treatment of bleeding episodes in haemophilia patients with inhibitors, is
      cleared from the circulation relatively fast with a plasma half-life of 2-4 h.
      PEGylation is an established and clinically proven strategy for prolonging the
      circulatory life-time of bio-therapeutic proteins. The aim of this study was to
      investigate the effect of glycoPEGylation of rFVIIa on rFVIIa binding to its
      cellular receptors and its subsequent internalization. rFVIIa and glycoPEGylated
      rFVIIa were labeled with (125)I and the radio-iodinated proteins were used to
      monitor rFVIIa binding and uptake in endothelial cells and fibroblasts. FVIIa-TF
      activity at the cell surface was analyzed by a factor X activation assay.
      Modification of rFVIIa with PEG impaired rFVIIa binding to both endothelial cell
      protein C receptor and tissue factor (TF) on cell surfaces. The internalization
      of PEGylated rFVIIa in endothelial cells and fibroblasts was markedly lower
      compared to the internalization of rFVIIa in these cells. PEGylated rFVIIa was
      able to activate factor X on TF expressing cell surfaces at a rate similar to
      that of unmodified rFVIIa when the cells were not subjected to multiple washings
      to remove the free ligand. General effects such as steric hindrance or changes in
      electrostatic binding properties of the modified rFVIIa to its receptors are
      probably responsible for this impairment rather than a loss of specific
      recognition of the receptors, which could explain near normal activation of
      factor X by glycoPEGylated rFVIIa on TF expressing cells while its uptake is
      reduced.

PMID- 19845777
TI  - To circumcise or not to circumcise? Circumcision in patients with bleeding
      disorders.
AB  - SUMMARY: Circumcision is one of the most common procedures performed in male
      neonates, but few published reports have described circumcision in patients with
      bleeding disorders. The aim of this study was to analyse outcomes of circumcision
      among children evaluated at our institution to determine the extent of
      complications and to provide guidelines for circumcision management. We searched
      our patient database for records of children who were followed up at the Mayo
      Clinic Comprehensive Hemophilia Center from 2000 through 2007 and who had been
      circumcised. We retrospectively reviewed the medical records to document
      complications and determine management strategies in this patient population. Of
      55 children and young adults identified (median [range] age, 15 years [11 months
      to 21 years]), 48 patients were circumcised. Indications for circumcision were
      parental request (n = 45) and medical recommendation (n = 3). Twelve of 21
      patients with a known bleeding disorder at the time of circumcision received
      factor replacement before the procedure. Three of these 21 patients had bleeding
      complications. Of the other 27 patients, who were diagnosed later in life as
      having a bleeding disorder, 8 had bleeding complications. The overall incidence
      of bleeding after circumcision was 23% (11/48). The 23% overall incidence of
      bleeding complications in our patients with bleeding disorders is comparable to
      that reported for patients without a bleeding disorder (0.1-35%). Some of our
      patients had significant bleeding despite adequate factor replacement before and
      after the procedure. Parents and patients must be aware that bleeding risk is a
      possibility despite adequate factor replacement for hemostasis.

PMID- 19845778
TI  - Development and validation of a new questionnaire for the assessment of
      subjective physical performance in adult patients with haemophilia--the HEP-Test
      Q.
AB  - Specific research studies for the investigation of physical performance in
      haemophilic patients are rare. However, these instruments become increasingly
      more important to evaluate therapeutic treatments. Within the frame of the
      Haemophilia & Exercise Project (HEP), a new questionnaire, namely HEP-Test-Q, has
      been developed for the assessment of subjective physical performance in
      haemophilic adults. In this article, the development and validation of the HEP
      Test-Q is described. The development consisted of different phases including item
      collection, pilot testing and field testing. The preliminary version was pilot
      tested in 24 German HEP-participants. Following evaluation and preliminary
      psychometric analysis, the HEP-Test-Q was revised. The final version consists of
      25 items pertaining to the domains 'mobility', 'strength & coordination',
      'endurance' and 'body perception', which was administered to 43 German
      haemophilic patients (43.8 +/- 11.2 years). Psychometric analysis included
      reliability and validity testing. Convergent validity was tested correlating the
      HEP-Test-Q with SF-36, Haem-A-QoL, HAL and the Orthopaedic Joint Score.
      Discriminant validity tested different clinical subgroups. Patients accepted the
      questionnaire and found it easy to fill in. Psychometric testing revealed good
      values for reliability in terms of internal consistency (Cronbach's alpha = 0.96)
      and test-retest reliability (r = 0.90) as well as for convergent validity
      correlating highly with Haem-A-QoL, HAL and SF-36. Discriminant validity testing
      showed significant differences for age, hepatitis A and hepatitis B and the
      number of target joints. HEP-Test-Q is a short and well-accepted questionnaire,
      assessing subjective physical performance of haemophiliacs, which might be
      combined with objective assessments to reveal aspects, which cannot be measured
      objectively, such as body perception.

PMID- 19845779
TI  - Anatomical variations in the circle of Willis and migraine susceptibility: is
      there an association?

PMID- 19845780
TI  - Childhood maltreatment and migraine (part III). Association with comorbid pain
      conditions.
AB  - OBJECTIVE: To evaluate in a headache clinic population the relationship of
      childhood maltreatment on the prevalence of pain conditions comorbid with
      migraine. BACKGROUND: Childhood maltreatment is highly prevalent and has been
      frequently associated with recurrent headache. The relationship of maltreatment
      and pain has, however, been a subject of some debate. METHODS: Cross-sectional
      data on self-reported physician-diagnosed pain conditions were electronically
      collected from persons with migraine (diagnosed according to International
      Classification of Headache Disorders-2), seeking treatment in headache clinics at
      11 centers across the US and Canada. These included irritable bowel syndrome
      (IBS), chronic fatigue syndrome (CFS), fibromyalgia (FM), interstitial cystitis
      (IC), arthritis, endometriosis, and uterine fibroids. Other information included
      demographics, migraine characteristics (frequency, headache-related disability),
      remote and current depression (The Patient Health Questionnaire-9), and remote
      and current anxiety (The Beck Anxiety Inventory). Patients also completed the
      Childhood Trauma Questionnaire regarding sexual, emotional, and physical abuse,
      and emotional and physical neglect under the age of 18 years old. Statistical
      analyses accounted for the survey design and appropriate procedures in SAS such
      as surveymeans, surveyfreq, and surveylogistic were applied to the weighted data.
      RESULTS: A total of 1348 migraineurs (88% women) were included in this study
      (mean age 41 years). Based on physician diagnosis or validated criteria, 31% had
      IBS, 16% had CFS, and 10% had FM. Diagnosis of IC was reported by 6.5%, arthritis
      by 25%, and in women, endometriosis was reported by 15% and uterine fibroids by
      14%. At least 1 comorbid pain condition was reported by 61%, 2 conditions by 18%,
      and 3 or more by 13%. Childhood maltreatment was reported by 58% of the patients.
      Emotional abuse was associated with increased prevalence of IBS, CFS, arthritis,
      and physical neglect with arthritis. In women, physical abuse was associated with
      endometriosis and physical neglect with uterine fibroids. Emotional abuse, and
      physical abuse and neglect (P < .0001 for all) were also associated with
      increased total number of comorbid conditions. In ordinal logistic regression
      models, adjusted for sociodemographics and current depression (prevalence 28%)
      and anxiety (prevalence 56%), emotional abuse (odds ratios [OR] = 1.69, 95%
      confidence intervals [CI]: 1.224-2.33) and physical neglect (OR = 1.73, 95% CI:
      1.22-2.46) were independently associated with an increased number of pain
      conditions. The cohort of women, similarly, had associations of emotional abuse
      (OR = 1.94, 95% CI: 1.40-2.72) and physical neglect (OR = 1.90, 95% CI: 1.34
      2.68) with an increased number of pain comorbidities. CONCLUSION: The association
      of childhood maltreatment and pain was stronger in those reporting multiple pain
      conditions and multiple maltreatment types. This finding suggests that in
      migraineurs childhood maltreatment may be a risk factor for development of
      comorbid pain disorders.

PMID- 19845781
TI  - Childhood maltreatment and migraine (part II). Emotional abuse as a risk factor
      for headache chronification.
AB  - OBJECTIVES: To assess in a headache clinic population the relationship of
      childhood abuse and neglect with migraine characteristics, including type,
      frequency, disability, allodynia, and age of migraine onset. BACKGROUND:
      Childhood maltreatment is highly prevalent and has been associated with recurrent
      headache. Maltreatment is associated with many of the same risk factors for
      migraine chronification, including depression and anxiety, female sex, substance
      abuse, and obesity. METHODS: Electronic surveys were completed by patients
      seeking treatment in headache clinics at 11 centers across the United States and
      Canada. Physician-determined data for all participants included the primary
      headache diagnoses based on the International Classification of Headache
      Disorders-2 criteria, average monthly headache frequency, whether headaches
      transformed from episodic to chronic, and if headaches were continuous. Analysis
      includes all persons with migraine with aura, and migraine without aura.
      Questionnaire collected information on demographics, social history, age at onset
      of headaches, migraine-associated allodynic symptoms, headache-related disability
      (The Headache Impact Test-6), current depression (The Patient Health
      Questionnaire-9), and current anxiety (The Beck Anxiety Inventory). History and
      severity of childhood (<18 years) abuse (sexual, emotional, and physical) and
      neglect (emotional and physical) was gathered using the Childhood Trauma
      Questionnaire. RESULTS: A total of 1348 migraineurs (88% women) were included
      (mean age 41 years). Diagnosis of migraine with aura was recorded in 40% and
      chronic headache (>or=15 days/month) was reported by 34%. Transformation from
      episodic to chronic was reported by 26%. Prevalence of current depression was 28%
      and anxiety was 56%. Childhood maltreatment was reported as follows: physical
      abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and
      emotional neglect 38%. In univariate analyses, physical abuse and emotional abuse
      and neglect were significantly associated with chronic migraine and transformed
      migraine. Emotional abuse was also associated with continuous daily headache,
      severe headache-related disability, and migraine-associated allodynia. After
      adjusting for sociodemographic factors and current depression and anxiety, there
      remained an association between emotional abuse in childhood and both chronic
      (odds ratio [OR] = 1.77, 95% confidence intervals [CI]: 1.19-2.62) and
      transformed migraine (OR = 1.89, 95% CI: 1.25-2.85). Childhood emotional abuse
      was also associated with younger median age of headache onset (16 years vs 19
      years, P = .0002). CONCLUSION: Our findings suggest that physical abuse,
      emotional abuse, and emotional neglect may be risk factors for development of
      chronic headache, including transformed migraine. The association of maltreatment
      and headache frequency appears to be independent of depression and anxiety, which
      are related to both childhood abuse and chronic daily headache. The finding that
      emotional abuse was associated with an earlier age of migraine onset may have
      implications for the role of stress responses in migraine pathophysiology.

PMID- 19845782
TI  - Childhood maltreatment and migraine (part I). Prevalence and adult
      revictimization: a multicenter headache clinic survey.
AB  - OBJECTIVES: To examine the prevalence of childhood maltreatment and adult
      revictimization in migraineurs and the association with sociodemographic factors,
      depression and anxiety. BACKGROUND: Population and practice-based studies have
      demonstrated an association of childhood abuse and headache in adults, although
      further details on headache diagnoses, characteristics, and comorbid conditions
      are lacking. There are mounting data suggesting substantial impact of early
      maltreatment on adult physical and mental health. METHODS: Electronic surveys
      were completed by patients seeking treatment in 11 headache centers across the
      United States and Canada. Physicians determined the primary headache diagnoses
      based on the International Classification of Headache Disorders-2 criteria and
      average monthly headache frequency. Self-reported information on demographics
      (including body mass index), social history, and physician-diagnosed depression
      and anxiety was collected. The survey also included validated screening measures
      for current depression (Patient Health Questionnaire-9) and anxiety (The Beck
      Anxiety Inventory). History and severity of childhood (<18 years) abuse (sexual,
      emotional, and physical) and neglect (emotional and physical) was gathered using
      the Childhood Trauma Questionnaire. There were also queries regarding adult
      physical and sexual abuse, including age of occurrence. Analysis includes all
      persons with migraine with aura, and migraine without aura. RESULTS: A total of
      1348 migraineurs (88% women) were included (mean age 41 years). Diagnosis of
      migraine with aura was recorded in 40% and chronic headache (>or=15 days/month)
      was reported by 34%. The prevalence of childhood maltreatment types was as
      follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical
      neglect 22%, and emotional neglect 38%. Nine percent reported all 3 categories of
      childhood abuse (physical, sexual, and emotional) and 17% reported both physical
      and emotional neglect. Overlap between maltreatment types ranged between 40% and
      81%. Of those reporting childhood abuse, 43% reported abuse in adulthood, but
      infrequently (17%) over the age of 30 years. In logistic regression models
      adjusted for sociodemographic variables, current depression was associated with
      physical (P = .003), sexual (P = .007), and emotional abuse (P < .001), and
      physical and emotional neglect (P = .001 for both). Current anxiety was also
      associated with all childhood abuse and neglect categories (P < .001 for all). A
      graded relationship was observed between the number of childhood maltreatment
      types and remote or current depression and anxiety. In adjusted logistic
      regression analysis, migraineurs reporting 3 or more categories of childhood
      trauma were more likely to have received diagnoses of both depression and anxiety
      (odds ratios [OR] = 6.91, 95% confidence interval [CI]: 3.97-12.03), or either
      depression or anxiety (OR = 3.66, 95% CI: 2.28-5.88) as compared with those
      without childhood abuse or neglect. CONCLUSION: Reports of childhood
      maltreatment, especially emotional abuse and neglect, are prevalent in
      outpatients with migraine. There is extensive overlap of maltreatment types and a
      high rate of revictimization in adulthood. All types of childhood abuse and
      neglect are strongly associated with remote and current depression and anxiety,
      and the relationship strengthens with an increasing number of maltreatment types.

PMID- 19845783
TI  - Trigeminal neuralgia and dural arteriovenous fistula in an edentulous man.

PMID- 19845785
TI  - Single nucleotide polymorphisms of the serotonin transporter gene in migraine--an
      association study.
AB  - We report a case-control study with 251 unrelated migraine patients and 192
      unrelated healthy controls to evaluate an association between the polymorphisms
      of the 5-HT transporter (5-HTT) gene rs2066713 and rs1979572 and different
      migraine phenotypes. We found a genetic association for the A allele of rs1979572
      for migraine with aura (MA) especially in women as well as a significant lower
      prevalence for MA for carrier of the A allele of rs2066713 in women. These
      findings support previous results suggesting that the 5-HTT gene is involved in
      the polygenic etiology of MA. These data further suggest that women are more
      likely to be clinically affected by mutations in the 5-HTT gene than men.

PMID- 19845784
TI  - Migraine and obesity: epidemiology, mechanisms, and implications.
AB  - Adipose tissue is a dynamic neuroendocrine organ that is involved in multiple
      physiological and pathological processes, and when excessive, results in obesity.
      Clinical and population-based data suggest that migraine and chronic daily
      headache are associated with obesity, as estimated by anthropometric indices. In
      addition, translational and basic science research shows multiple areas of
      overlap between migraine pathophysiology and the central and peripheral pathways
      regulating feeding. Specifically, neurotransmittors such as serotonin, peptides
      such as orexin, and adipocytokines such as adiponectin and leptin have been
      suggested to have roles in both feeding and migraine. In this article, we first
      review the definition and ascertainment of obesity. This is followed by a review
      of the clinical and population-based studies evaluating the associations between
      obesity and chronic daily headache and migraine. We then discuss the central and
      peripheral pathways involved in the regulation of feeding, where it overlaps with
      migraine pathophysiology, and where future research may be headed in light of
      these data.

PMID- 19845786
TI  - SUNCT responsive to percutaneous balloon compression of the gasserian ganglion-
      10-year follow-up.
AB  - We report the case of a woman with short-lasting unilateral, neuralgiform
      headache attacks with conjunctival injection and tearing (SUNCT) whose severe
      headache attacks ceased after percutaneous balloon compression of the Gasserian
      ganglion. The patient remains pain free after 10-year follow-up. This may be the
      first literature report of SUNCT in Chile.

PMID- 19845787
TI  - Capillary endothelial Na(+), K(+), ATPase transporter homeostasis and a new
      theory for migraine pathophysiology.
AB  - BACKGROUND: Cerebrospinal fluid sodium concentration ([Na(+)](csf)) increases
      during migraine, but the cause of the increase is not known. OBJECTIVE: Analyze
      biochemical pathways that influence [Na(+)](csf) to identify mechanisms that are
      consistent with migraine. METHOD: We reviewed sodium physiology and biochemistry
      publications for links to migraine and pain. RESULTS: Increased capillary
      endothelial cell (CEC) Na(+), K(+), -ATPase transporter (NKAT) activity is
      probably the primary cause of increased [Na(+)](csf). Physiological fluctuations
      of all NKAT regulators in blood, many known to be involved in migraine, are
      monitored by receptors on the luminal wall of brain CECs; signals are then
      transduced to their abluminal NKATs that alter brain extracellular sodium
      ([Na(+)](e)) and potassium ([K(+)](e)). CONCLUSIONS: We propose a theoretical
      mechanism for aura and migraine when NKAT activity shifts outside normal limits:
      (1) CEC NKAT activity below a lower limit increases [K(+)](e), facilitates
      cortical spreading depression, and causes aura; (2) CEC NKAT activity above an
      upper limit elevates [Na(+)](e), increases neuronal excitability, and causes
      migraine; (3) migraine-without-aura may arise from CEC NKAT over-activity without
      requiring a prior decrease in activity and its consequent spreading depression;
      (4) migraine triggers disturb, and treatments improve, CEC NKAT homeostasis; (5)
      CEC NKAT-induced regulation of neural and vasomotor excitability coordinates
      vascular and neuronal activities, and includes occasional pathology from CEC NKAT
      induced apoptosis or cerebral infarction.

PMID- 19845788
TI  - Lack of efficacy of manual therapy in children and adolescents with suspected
      cervicogenic headache: results of a prospective, randomized, placebo-controlled,
      and blinded trial.
AB  - OBJECTIVE: Clinical trials concerning cervical spine manipulation and
      mobilization in children and adolescents with cervicogenic headache are lacking.
      METHODS: We performed a multicenter, prospective, randomized, placebo-controlled,
      and blinded trial in 52 children and adolescents (21 boys, 31 girls) aged 7-15.
      After prospective baseline documentation for 2 months patients were either
      assigned to placebo or true manipulation with another 2-month follow-up. Main
      outcome measures were defined as: percentage of days with headache, total
      duration of headache, days with school absence due to headache, consume of
      analgesics, intensity of headache. RESULTS: We did not find a significant
      difference comparing the groups with placebo and true manipulation with respect
      to the defined main outcome measures. CONCLUSIONS: We were not able to show an
      efficacy of cervical spine manipulation in 52 children and adolescents.

PMID- 19845789
TI  - Distribution of artemin and GFRalpha3 labeled nerve fibers in the dura mater of
      rat: artemin and GFRalpha3 in the dura.
AB  - OBJECTIVE: We examined the distribution of artemin and its receptor, glial cell
      line-derived neurotrophic factor family receptor alpha3 (GFRalpha3), in the dura
      mater of rats. BACKGROUND: Artemin, a member of the glial cell line-derived
      neurotrophic factor family, is a vasculature-derived growth factor shown to
      regulate migration of sympathetic neuroblasts and targeting of sympathetic
      innervation. The artemin receptor, GFRalpha3, is present in both sympathetic
      efferents and a subpopulation of nociceptive afferents. Recent evidence has shown
      that artemin may contribute to inflammatory hyperalgesia. The extent to which
      artemin is present in the dural vasculature and its relationship to GFRalpha3
      containing fibers have yet to be investigated. METHODS: We used retrograde
      labeling, double and triple labeling with immunohistochemistry on the dura mater
      and trigeminal ganglia of female Sprague-Dawley rats. RESULTS: Artemin-like
      immunoreactivity (-LI) was detected in the smooth muscle of dural vasculature.
      GFRalpha3-LI was present in nerve fibers that closely associated with tyrosine
      hydroxylase or calcitonin gene-related peptide (CGRP). CGRP-LI and transient
      receptor potential ion channel 1 (TRPV1)-LI were present in all GFRalpha3
      positive dural afferents, which constituted 22% of the total population of dural
      afferents. CONCLUSIONS: These anatomical results support the hypothesis that
      artemin contributes to dural afferent activity, and possibly migraine pain,
      through modulation of both primary afferent and sympathetic systems.

PMID- 19845790
TI  - Histological grading of invasive breast carcinoma--a simplification of existing
      methods in a large conservation series with long-term follow-up.
AB  - AIMS: To assess the validity of grading in the Edinburgh Breast Conservation
      Series; a consecutive cohort of 1812 early breast cancer patients treated by
      breast conservation and radiotherapy between 1981 and 1998 in a single specialist
      centre with > or =9 years' follow-up and full staging data. METHODS AND RESULTS:
      A single pathologist (J.St.J.T) graded 1650 cases using the Elston and Ellis
      method (EE) with particular reference to the component data: acinar
      differentiation, nuclear pleomorphism and mitotic counts. The original method was
      then compared with binary scoring of the same components and the relationship to
      prognosis reassessed. EE grades and individual grade components were prognostic
      (P < 0.0001) with 10-year cause-specific survival of 95.6%, 86.4% and 74.7% for
      EE grades 1, 2 and 3, respectively. A binary scoring of grade components produces
      four groups, splitting EE grade 2 tumours into two groups with different outcomes
      -10-year survival rates for the four revised grades were 96.0%, 89.0%, 79.7% and
      75.4%, respectively. CONCLUSIONS: Existing grading methodology is fully
      applicable in the narrower context of a conservation series but can be
      simplified. Subdivision of EE grade 2 into a true intermediate prognosis group
      and a second group with a worse prognosis also adds benefit.

PMID- 19845791
TI  - Quantitative measurement of venous invasion of colorectal cancer with
      metachronous liver metastasis.
AB  - AIMS: Many studies have proven the importance of venous invasion in colorectal
      cancer with synchronous liver metastasis. The aim was to clarify the relationship
      between venous invasion and metachronous liver metastasis, which is not fully
      understood. METHODS AND RESULTS: A histological study of venous invasion in
      colorectal carcinoma was performed using a total of 156 patients, of whom 52
      survived without recurrence for 5 years (Group A); 47 had metachronous liver
      metastasis (Group B), and 57 had synchronous liver metastasis (Group C). The
      number and the maximum area of venous invasion were estimated in each case per x
      40 field of cancerous lesions, which were divided into intramural and extramural
      lesions. A high incidence and high average number of foci of venous invasion
      appeared in Groups B and C. The average maximum areas of extramural venous
      invasion were much larger in Groups B and C than in Group A. CONCLUSIONS: The
      average number of foci of venous invasion by colorectal cancer with metachronous
      liver metastasis did not differ significantly from that with synchronous ones.
      Furthermore, invasion into extramural large veins appeared to be associated with
      liver metastasis.

PMID- 19845792
TI  - Nonconcordance between subclinical atherosclerosis and the calculated Framingham
      risk score in HIV-infected patients: relationships with serum markers of
      oxidation and inflammation.
AB  - OBJECTIVES: HIV-infected patients show an increased cardiovascular disease (CVD)
      risk resulting, essentially, from metabolic disturbances related to chronic
      infection and antiretroviral treatments. The aims of this study were: (1) to
      evaluate the agreement between the CVD risk estimated using the Framingham risk
      score (FRS) and the observed presence of subclinical atherosclerosis in HIV
      infected patients; (2) to investigate the relationships between CVD and plasma
      biomarkers of oxidation and inflammation. METHODS: Atherosclerosis was evaluated
      in 187 HIV-infected patients by measuring the carotid intima-media thickness
      (CIMT). CVD risk was estimated using the FRS. We also measured the circulating
      levels of interleukin-6, monocyte chemoattractant protein-1 (MCP-1) and oxidized
      low-density lipoprotein (LDL), and paraoxonase-1 activity and concentration.
      RESULTS: There was a weak, albeit statistically significant, agreement between
      FRS and CIMT (kappa=0.229, P<0.001). A high proportion of patients with an
      estimated low risk had subclinical atherosclerosis (n=66; 56.4%). In a
      multivariate analysis, the presence of subclinical atherosclerosis in this
      subgroup of patients was associated with age [odds ratio (OR) 1.285; 95%
      confidence interval (CI) 1.084-1.524; P=0.004], body mass index (OR 0.799; 95% CI
      0.642-0.994; P=0.044), MCP-1 (OR 1.027; 95% CI 1.004-1.050; P=0.020) and oxidized
      LDL (OR 1.026; 95% CI 1.001-1.051; P=0.041). CONCLUSION: FRS underestimated the
      presence of subclinical atherosclerosis in HIV-infected patients. The increased
      CVD risk was related, in part, to the chronic oxidative stress and inflammatory
      status associated with this patient population.

PMID- 19845793
TI  - Eosinophils infiltrate thyroids, but have no apparent role in induction or
      resolution of experimental autoimmune thyroiditis in interferon-gamma(-/-) mice.
AB  - Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse
      thyroglobulin (MTg)-sensitized splenocytes activated with MTg and interleukin
      (IL)-12. Our previous studies showed that, when used as donors and recipients,
      interferon (IFN)-gamma(-/-) and wild-type (WT) DBA/1 mice both develop severe G
      EAT. Thyroid lesions in IFN-gamma(-/-) mice have many eosinophils and few
      neutrophils, while those in WT mice have extensive neutrophil infiltration and
      few eosinophils. Thyroid lesions in IFN-gamma(-/-) mice consistently resolve by
      day 40-50, whereas those in WT mice have ongoing inflammation and fibrosis
      persisting for more than 60 days. To determine if the extensive infiltration of
      eosinophils in thyroids of IFN-gamma(-/-) mice contributes to thyroid damage
      and/or early resolution of G-EAT, anti-IL-5 was used to inhibit migration of
      eosinophils to thyroids. G-EAT severity was compared at day 20 and day 40-50 in
      IFN-gamma(-/-) recipients given anti-IL-5 or control immunoglobulin G (IgG).
      Thyroids of anti-IL-5-treated IFN-gamma(-/-) mice had few eosinophils and more
      neutrophils at day 20, but G-EAT severity scores were comparable to those of
      control IgG-treated mice at both day 20 and day 40-50. Expression of chemokine (C
      X-C motif) ligand 1 (CXCL1) mRNA was higher and that of chemokine (C-C motif)
      ligand 11 (CCL11) mRNA was lower in thyroids of anti-IL-5-treated IFN-gamma(-/-)
      mice. IL-5 neutralization did not influence mRNA expression of most cytokines in
      IFN-gamma(-/-) mice. Thus, inhibiting eosinophil migration to thyroids did not
      affect G-EAT severity or resolution in IFN-gamma(-/-) mice, suggesting that
      eosinophil infiltration of thyroids occurs as a consequence of IFN-gamma
      deficiency, but these cells have no apparent pathogenic role in G-EAT.

PMID- 19845794
TI  - Clonal relationships between thyroid-stimulating hormone receptor-stimulating
      antibodies illustrate the effect of hypermutation on antibody function.
AB  - Graves' disease is characterized by production of agonist antibodies to the
      thyroid-stimulating hormone receptor (TSHR), but knowledge of the genetic and
      somatic events leading to their aberrant production is limited. We describe the
      genetic analysis of two monoclonal antibodies (mAbs) with thyroid-stimulating
      activity (TSAb) obtained from a single mouse with experimental Graves' disease.
      The mAbs were class switched, but used the same rearrangement of immunoglobulin
      heavy chain, variable region (IGHV) and immunoglobulin light chain, variable
      region (IGLV) germline genes, implying a clonal relationship and derivation from
      a single precursor B-cell clone. The IGHV-region genes of the two mAbs underwent
      high degrees of somatic hypermutation by sharing numerous mutations before
      diverging, while the IGLV genes evolved separately. Interestingly, the mutations
      were present in both the complementarity-determining regions (CDRs) and the
      framework regions. The cloned IGHV and IGLV genes were confirmed to have TSAb
      properties in experiments in which they were expressed as recombinant Fabs
      (rFabs). In other experiments, we swapped the IGLV genes with IGHV genes by
      constructing chimeric rFabs and showed that the chimeras retained TSAb
      activities, confirming the close functional relatedness of the V-region genes.
      Importantly, the IGLV genes in chimeric rFabs had a dominant stimulatory effect
      at low concentrations, while the IGHV genes had a dominant effect at higher
      concentrations. Our findings demonstrate that, in experimentally immunized mice,
      multiple pathogenic antibodies to TSHR can arise from a single clone by a series
      of somatic mutations in the V-region genes and may give an insight into how such
      antibodies develop spontaneously in autoimmune Graves' disease.

PMID- 19845795
TI  - The self-antigen, thyroglobulin, induces antigen-experienced CD4+ T cells from
      healthy donors to proliferate and promote production of the regulatory cytokine,
      interleukin-10, by monocytes.
AB  - Thyroglobulin (TG), as autoantigen, induces in vitro proliferation of T and B
      cells from normal individuals, but the cytokine production differs from that in
      patients with autoimmune thyroid disease. Here, we investigate whether normal T
      cells responding to TG are naive, or have previously encountered TG in vivo,
      using their responses to classic primary and secondary antigens, keyhole limpet
      haemocyanin (KLH) and tetanus toxoid (TT), respectively, for comparison. While TG
      elicited T-cell proliferation kinetics typical of a secondary response, the
      cytokine profile was distinct from that for TT. Whereas TT induced pro
      inflammatory cytokines [interleukin-2 (IL-2)/interferon-gamma (IFN-gamma)/IL-4/IL
      5], TG evoked persistent release of the regulatory IL-10. Some donors, however,
      also responded with late IFN-gamma production, suggesting that the regulation by
      IL-10 could be overridden. Although monocytes were prime producers of IL-10 in
      the early TG response, a few IL-10-secreting CD4(+) T cells, primarily with
      CD45RO(+) memory phenotype, were also detected. Furthermore, T-cell depletion
      from the mononuclear cell preparation abrogated monocyte IL-10 production. Our
      findings indicate active peripheral tolerance towards TG in the normal
      population, with aberrant balance between pro- and anti-inflammatory cytokine
      responses for some donors. This observation has implications for autoantigen
      recognition in general, and provides a basis for investigating the dichotomy
      between physiological and pathological modes of auto-recognition.

PMID- 19845796
TI  - Migration of immature and mature B cells in the aged microenvironment.
AB  - Studies in aged mice show that the architecture of B-cell areas appears disrupted
      and that newly made B cells fail to incorporate into the spleen. These
      observations may reflect altered migration of immature and mature B cells. Using
      adoptive transfer, we tested the effect of the aged microenvironment and the
      intrinsic ability of donor B cells from aged mice to migrate to spleens of intact
      hosts. Spleens of aged recipients were deficient in attracting young or old donor
      immature B cells. In contrast, immature and mature B cells maintained an
      intrinsic ability to migrate to young recipient spleens, except that as the aged
      immature B cells matured, fewer appeared to enter the recirculating pool. CXCL13
      protein, which is necessary for the organization of B-cell compartments, was
      elevated with age and differences in CXCL13 distribution were apparent. In aged
      spleens, CXCL13 appeared less reticular, concentrated in patches throughout the
      follicles, and notably reduced in the MAdCAM-1(+) marginal reticular cells
      located at the follicular edge. Despite these differences, the migration of young
      donor follicular B cells into the spleens of old mice was not impacted; whereas,
      migration of young donor marginal zone B cells was reduced in aged recipients.
      Finally, the aged bone marrow microenvironment attracted more donor mature B
      cells than did the young marrow. Message for CXCL13 was not elevated in the
      marrow of aged mice. These results suggest that the aged splenic microenvironment
      affects the migration of immature B cells more than mature follicular B cells.

PMID- 19845797
TI  - Auxiliary role for D-alanylated wall teichoic acid in Toll-like receptor 2
      mediated survival of Staphylococcus aureus in macrophages.
AB  - We previously reported that Staphylococcus aureus avoids killing within
      macrophages by exploiting the action of Toll-like receptor 2 (TLR2), which leads
      to the c-Jun N-terminal kinase (JNK)-mediated inhibition of superoxide
      production. To search for bacterial components responsible for this event, a
      series of S. aureus mutants, in which the synthesis of the cell wall was
      interrupted, were screened for the level of JNK activation in macrophages. In
      addition to a mutant lacking the lipoproteins that have been suggested to act as
      a TLR2 ligand, two mutant strains were found to activate the phosphorylation of
      JNK to a lesser extent than the parental strain, and this defect was recovered by
      acquisition of the corresponding wild-type genes. Macrophages that had
      phagocytosed the mutant strains produced more superoxide than those engulfing the
      parental strain, and the mutant bacteria were more efficiently killed in
      macrophages than the parent. The genes mutated, dltA and tagO, encoded proteins
      involved in the synthesis of D-alanylated wall teichoic acid. Unlike a cell wall
      fraction rich in lipoproteins, D-alanine-bound wall teichoic acid purified from
      the parent strain by itself did not activate JNK phosphorylation in macrophages.
      These results suggest that the d-alanylated wall teichoic acid of S. aureus
      modulates the cell wall milieu for lipoproteins so that they effectively serve as
      a ligand for TLR2.

PMID- 19845799
TI  - Caffeine induces ram sperm hyperactivation independent of cAMP-dependent protein
      kinase.
AB  - We have previously shown that a cocktail-containing phosphodiesterase inhibitors
      (theophylline and caffeine), a phosphatase inhibitor (okadaic acid) and dibutyryl
      cAMP promoted specific protein tyrosine phosphorylation in ram spermatozoa during
      incubation in capacitating conditions. Here, we show, for the first time, that
      this cocktail induced a progressive time-dependent increase in the capacitated
      sperm subpopulation. The addition of either the analogue of adenosine, 2-chloro
      2'-deoxyadenosine (Cl-Ado) or caffeine provided a significant increase in the
      proportion of capacitated spermatozoa and total tyrosine phosphorylation.
      Computer-assisted semen analysis was used to identify hyperactivated spermatozoa
      by setting maximum threshold for linearity (< or =45%) and minimum for amplitude
      of lateral head displacement (> or =3.5 microm). Our results showed that ram
      spermatozoa can be capacitated in vitro without displaying hyperactivated
      movement. Among the above-mentioned compounds, only caffeine was able to induce
      hyperactivation that achieved the maximal response at 8 min of incubation, with a
      significant increase in hyperactivated spermatozoa of 44.4 +/- 5.6% related to
      control samples. Flow cytometry analyses showed that caffeine induced a
      significant increase in the content of calcium in viable spermatozoa during the
      time-course of incubation in capacitating conditions. BAPTA-AM, a cell-permeable
      calcium chelator, did not suppress the caffeine-dependent hyperactivation.
      Quantitative analysis revealed that the addition of caffeine or Cl-Ado accounted
      for an increase in intracellular cAMP level. However, this increase in cAMP does
      not seem to be responsible for the caffeine-induced hyperactivation because the
      cAMP-elevating agents (cocktail) did not promote hyperactivation either, although
      they greatly induced capacitation and protein tyrosine phosphorylation. The
      inhibition of PKA with H89 reduced both capacitation and protein tyrosine
      phosphorylation although hyperactivation increased. These results suggest that
      calcium from internal stores would be enough to initiate the hyperactivated
      movement, and that protein tyrosine phosphorylation implicated in ram sperm
      hyperactivation would be regulated by calcium rather than by PKA-dependent cAMP.

PMID- 19845798
TI  - Protease-activated receptor 2 signalling promotes dendritic cell antigen
      transport and T-cell activation in vivo.
AB  - Deficiency of protease-activated receptor-2 (PAR2) modulates inflammation in
      several models of inflammatory and autoimmune disease, although the underlying
      mechanism(s) are not understood. PAR2 is expressed on endothelial and immune
      cells, and is implicated in dendritic cell (DC) differentiation. We investigated
      in vivo the impact of PAR2 activation on DCs and T cells in PAR2 wild-type (WT)
      and knockout (KO) mice using a specific PAR2 agonist peptide (AP2). PAR2
      activation significantly increased the frequency of mature CD11c(high) DCs in
      draining lymph nodes 24 hr after AP2 administration. Furthermore, these DCs
      exhibited increased expression of major histocompatibility complex (MHC) class II
      and CD86. A significant increase in activated (CD44(+) CD62(-)) CD4(+) and CD8(+)
      T-cell frequencies was also observed in draining lymph nodes 48 hr after AP2
      injection. No detectable change in DC or T-cell activation profiles was observed
      in the spleen. The influence of PAR2 signalling on antigen transport to draining
      lymph nodes was assessed in the context of delayed-type hypersensitivity. PAR2 WT
      mice that were sensitized by skin-painting with fluorescein isothiocyanate (FITC)
      to induce delayed-type hypersensitivity possessed elevated proportion of FITC(+)
      DCs in draining lymph nodes 24 hr after FITC painting when compared with PAR2 KO
      mice (0.95% versus 0.47% of total lymph node cells). Collectively, these results
      demonstrate that PAR2 signalling promotes DC trafficking to the lymph nodes and
      subsequent T-cell activation, and thus provides an explanation for the pro
      inflammatory effect of PAR2 in animal models of inflammation.

PMID- 19845800
TI  - The predictive value of testicular ultrasound abnormalities for carcinoma in situ
      of the testis in men at risk for testicular cancer.
AB  - Testicular microlithiasis (TM) is sometimes observed during scrotal ultrasound
      examinations in men. It has been suggested that TM is more prevalent in testes of
      men at risk for testicular carcinoma in situ (CIS), the precursor cells of all
      testicular germ cell tumours (TGCT). We have performed a retrospective analysis
      of ultrasound images and additional clinical data of a selected cohort of men and
      have determined the risk factor of TM and other ultrasound abnormalities for
      testicular CIS. Between 2002 and 2007, 176 testicular biopsies were performed in
      men with abnormalities found on the scrotal ultrasound. TM was found in 76/176
      men (43.2%) and CIS was diagnosed in 20 of these men (26.3%). Here, we focused on
      the group of 76 men with TM to determine additional risk factors, besides TM, for
      CIS. In both groups, those with and without CIS, reproductive hormones, scrotal
      ultrasound images and patient history were compared. Predictive ultrasound
      findings for CIS were TM (sensitivity 100%, 95% CI: 0.8-1.0; specificity 64.1%,
      95% CI: 0.6-0.7; PPV 26.3%, 95% CI: 0.2-0.4) and within this group an
      inhomogeneous testicular parenchyma (OR 16.1, 95% CI 2.4-106.8; sensitivity
      75.0%, 95% CI: 0.5-0.9; specificity 79.0%, 95% CI: 0.7-0.9; PPV 50.0%, 95% CI:
      0.3-0.7). Other significantly ultrasound characteristics for CIS in this
      population with TM were clusters of TM (p = 0.02) and intra-testicular lesions (p
      = 0.01). Men with CIS were found to have significantly lower values of inhibin-B
      (p = 0.02). Clusters of TM, intra-testicular lesions and lower values of inhibin
      B were not significantly different in logistic regression analysis. TM on scrotal
      ultrasound of men with risk factors for TGCT and men with clinical signs of
      testicular maldevelopment has a high predictive value for CIS. However, the
      predictive value of an inhomogeneous testicular parenchyma, besides TM, for CIS
      is much higher.

PMID- 19845801
TI  - The delicate balance between male and female sex determining pathways: potential
      for disruption of early steps in sexual development.
AB  - Testes and ovaries develop from the same primordial structures, the genital
      ridges, in the mammalian foetus. Male development depends critically on the
      correct functioning of the Y-linked testis-determining gene, Sry. However, Sry is
      highly vulnerable to mutation, and so does not provide a very robust sex
      determining mechanism. Both in testes and in ovaries, proper gonadal development
      involves co-ordinated regulation of the bipotential fates of a number of
      different cell lineages, and is dependent on intercellular signalling mechanisms.
      If either the testicular or ovarian pathway stalls in the early stages,
      mechanisms operate to engage the alternative pathway. For these reasons, the
      early steps in mammalian sexual development are vulnerable to genetic and
      environmental perturbation, and represent possible points of action of endocrine
      disrupting compounds.

PMID- 19845802
TI  - Osteoporosis management: a perspective based on bisphosphonate data from
      randomised clinical trials and observational databases.
AB  - AIMS: The efficacy of treatments for osteoporosis can be evaluated using a
      variety of study designs. This article aims to comprehensively review the
      evidence for bisphosphonate anti-fracture efficacy in postmenopausal women,
      discussing the strengths and limitations associated with each study method.
      METHODS: Literature analysis included English-language publications reporting
      results of randomised controlled trials (RCTs), post hoc analyses, meta analyses
      and observational studies evaluating the efficacy of alendronate (ALN),
      ibandronate (IBN), risedronate (RIS) and zoledronate (ZOL), with an initial
      sample size > or = 100 patients, and follow-up data for at least 1 year. RESULTS:
      Primary and secondary analyses of RCT data suggest differences among
      bisphosphonates with regard to site-specific anti-fracture efficacy and onset of
      fracture risk reduction. While some observational studies indicate differences in
      clinical outcomes among these agents, others report similar effectiveness. ALN
      and RIS data demonstrate sustained fracture protection for up to 10 and 7 years
      of treatment respectively. The efficacy of IBN and ZOL has been evaluated for up
      to 3 and 5 years respectively. CONCLUSIONS: Understanding of the benefits of
      bisphosphonate treatment can be maximised by evaluating complementary data from
      RCTs and observational database studies. Fracture risk reduction with
      bisphosphonates is shown in RCTs and in real-world clinical settings.

PMID- 19845803
TI  - The differential diagnosis and management of asthma in the preschool-aged child.
AB  - PURPOSE: To discuss the diagnosis and management of asthma in preschool-aged
      children by nurse practitioners in primary care. DATA SOURCES: Selected research
      and clinical articles; 2007 National Asthma Education and Prevention Program
      Guidelines for the Diagnosis and Management of Asthma. CONCLUSIONS: Proper
      diagnosis leads to appropriate treatment of asthma in preschool-aged children,
      which facilitates asthma control. Well-controlled asthma results in fewer asthma
      exacerbations, fewer nighttime awakenings, and an increased ability to engage in
      normal childhood activities. IMPLICATIONS FOR PRACTICE: Advanced practice nurses
      are in the position to aid in the initial diagnosis of asthma in preschool-aged
      children through taking detailed medical histories, providing thorough physical
      examinations, and, if needed, initiating a therapeutic trial with an inhaled
      corticosteroid. Proper diagnosis and management of asthma is essential to reduce
      asthma complications, such as exacerbations leading to emergency department
      visits and hospitalizations.

PMID- 19845804
TI  - Risks and benefits of parent/child bed sharing.
AB  - PURPOSE: To recognize the concerns for and against parent/child bed-sharing (co
      sleeping) practices. DATA SOURCES: Review of the literature and the clinical
      experiences of the authors. CONCLUSIONS: The decision to bed share ultimately
      lies with the parent, but it is the responsibility of the nurse practitioner (NP)
      to discuss risks and benefits of parent preferences and to help families make a
      safe decision regarding the sleeping arrangement for their child. IMPLICATIONS
      FOR PRACTICE: If NPs know the benefits and risks regarding co-sleeping and bed
      sharing, they can better promote safe and culturally congruent family centered
      care.

PMID- 19845805
TI  - Emerging concepts in cardiovascular disease risk assessment: where do women fit
      in?
AB  - PURPOSE: To highlight the current limitations in the assessment of cardiovascular
      disease (CVD) risk for women. This article will offer the reader information on
      the current process for assessing CVD risk in women, the pitfalls associated with
      this current strategy, and the role of novel risk factors. DATA SOURCES:
      Extensive review of the medical literature in the area of women's cardiovascular
      health. CONCLUSIONS: The assessment of CVD risk for women is currently an
      evolving science. Limitations in the ability of the Framingham score to
      accurately estimate risk in women from diverse populations are increasingly
      recognized. Vastly different treatment goals between the genders for similar
      levels of risk factors have led to a re-evaluation of this strategy in women.
      While the Framingham score is still useful for guiding cholesterol treatment
      goals, the current preventive guidelines for women emphasize assessing a woman's
      risk throughout her lifetime. The future development of tools for improved risk
      stratification that incorporate novel risk factors may in fact improve our
      ability to appropriately risk stratify women to evidence-based therapies.
      IMPLICATIONS FOR PRACTICE: Utilizing the Framingham Risk Assessment Tool and
      further CVD risk stratification using novel markers such as high sensitivity C
      reactive protein, family history, and functional capacity may identify unique
      subsets of women at higher risk for CVD. Nurse practitioners can be instrumental
      in this assessment, education, and treatment of women at risk for CVD.

PMID- 19845806
TI  - Childhood and adolescent attention-deficit hyperactivity disorder: diagnosis,
      clinical practice guidelines, and social implications.
AB  - PURPOSE: To review the diagnostic criteria for attention-deficit hyperactivity
      disorder (ADHD), present an overview of the effects that ADHD has on family
      dynamics, school performance, and substance abuse, and provide an overview of the
      American Academy of Pediatrics (AAP) clinical practice and treatment guidelines.
      DATA SOURCES: An extensive health science literature review was carried out using
      PubMed and Cumulative Index to Nursing and Allied Health Literature. Other
      information was collected by searching reference lists of published reports.
      CONCLUSIONS: The diagnostic criteria and guidelines are important to make an
      accurate clinical assessment and manage a child with ADHD. Early diagnosis and
      treatment of ADHD decreases academic failure, family conflict, social isolation,
      substance abuse, and occupational adversity in later years for these children.
      IMPLICATIONS FOR PRACTICE: Often primary care nurse practitioners are the first
      healthcare provider a child with ADHD will see. Awareness of the diagnostic
      criteria and treatment for children with ADHD can assist with early
      identification and perhaps eliminate much impairment that accompanies this
      chronic disorder.

PMID- 19845807
TI  - Female sexual dysfunction: a primary care perspective.
AB  - PURPOSE: To discuss the incidence and prevalence of sexual dysfunction among
      women, some common etiologies, and patient-provider relationships that seem to
      inhibit successful resolution of female sexual dysfunction. DATA SOURCES: A
      selective review of the literature on female sexual dysfunction, and an overview
      of assessment tools that can be used to evaluate and monitor its treatment.
      CONCLUSION: Sexual dysfunction in women is a health issue often overlooked by
      medical personnel, but it is a topic of great importance to both the patient and
      her sexual partner(s). It has been well established that quality of sex, that is,
      satisfaction with one's sex life, is a major quality-of-life indicator. But
      specifically as concerns the female patient, the issue has been overlooked by
      much of the healthcare community, perhaps because the topic of female sexual
      dysfunction is multifaceted and complex in nature. IMPLICATIONS FOR PRACTICE:
      Clinicians have an obligation to develop self-awareness and clinical intuition to
      address the topic in the utmost professional manner.

PMID- 19845808
TI  - Getting to the heart of pleural effusions: a case study.
AB  - PURPOSE: To provide nurse practitioners (NPs) with an overview of the physiology,
      pathophysiology, clinical presentation, and comprehensive assessment, as well as
      the differential diagnosis process and initial management of patients with
      unilateral pleural effusions. DATA SOURCES: A review of the scientific literature
      was performed on pleural effusions, using Pub Med, Medline, and CINAHL. The case
      study of a patient with a pleural effusion related to heart failure is used to
      integrate this knowledge into clinical practice. CONCLUSIONS: Pleural effusions
      are common sequelae of numerous pathophysiological processes. IMPLICATIONS FOR
      PRACTICE: Knowledge of the underlying physiological and pathophysiological
      mechanisms enables the NP to obtain an accurate and comprehensive assessment,
      establishes a differential diagnosis, and provides the timely initial management
      necessary to optimize patient care outcomes.

PMID- 19845809
TI  - Level of autonomy of primary care nurse practitioners.
AB  - PURPOSE: The purpose of this descriptive study was to determine the level of
      autonomy of nurse practitioners (NPs) providing care to patients in a primary
      care setting. DATA SOURCES: Data were collected from 48 primary care NPs (PCNPs)
      who attended a state clinical conference. The Dempster Practice Behavior Scale
      (DPBS) was used to measure the autonomy of the NPs. CONCLUSIONS: The total mean
      score for the DPBS in this study was 127 (SD = 10.25), indicating a very high
      level of autonomy of the NPs. The Empowerment subscale had the lowest overall
      mean score, and the Valuation subscale had the highest. There was no
      statistically significant relationship between level of autonomy and age, years
      worked as an RN, and years worked as an NP. IMPLICATIONS FOR PRACTICE: This study
      provided evidence that PCNPs are highly autonomous professionals and continue to
      struggle with empowerment. NPs educationally prepared with a better knowledge of
      legal and political issues will be better suited to influence healthcare reform.
      NPs, as autonomous professionals, will be more likely to impact and shape future
      healthcare policy.

PMID- 19845810
TI  - Culturally tailored education to promote lifestyle change in Mexican Americans
      with type 2 diabetes.
AB  - PURPOSE: The purpose of this article is to report the results of a culturally
      tailored diabetes intervention for Mexican Americans on physical activity and to
      report the results of a focus group with intervention participants. DATA SOURCES:
      Seventeen Mexican American subjects with type 2 diabetes participated in the
      study. The study used a pretest/posttest control group design with 10 subjects in
      each group (N = 20). Outcome measures included the number of steps walked weekly,
      weight, and body mass index (BMI). Pedometers were used to measure the daily
      number of steps in the intervention group. A focus group provided data on
      participant satisfaction. CONCLUSIONS: Results suggest a positive effect of the
      intervention on physical activity level, weight, and sense of control over
      diabetes self-management. Intervention participants had a statistically
      significant increase in the number of steps walked per day and a statistically
      significant mean weight loss of five pounds. Focus group results indicate that
      participants were satisfied with the culturally tailored intervention and that
      they and their families benefited from the intervention. IMPLICATIONS FOR
      PRACTICE: A culturally tailored diabetes self-management program may result in
      improved outcomes for Mexican Americans with type 2 diabetes.

PMID- 19845811
TI  - Allometric functional response model: body masses constrain interaction
      strengths.
AB  - 1. Functional responses quantify the per capita consumption rates of predators
      depending on prey density. The parameters of these nonlinear interaction strength
      models were recently used as successful proxies for predicting population
      dynamics, food-web topology and stability. 2. This study addressed systematic
      effects of predator and prey body masses on the functional response parameters
      handling time, instantaneous search coefficient (attack coefficient) and a
      scaling exponent converting type II into type III functional responses. To fully
      explore the possible combinations of predator and prey body masses, we studied
      the functional responses of 13 predator species (ground beetles and wolf spiders)
      on one small and one large prey resulting in 26 functional responses. 3. We found
      (i) a power-law decrease of handling time with predator mass with an exponent of 
      0.94; (ii) an increase of handling time with prey mass (power-law with an
      exponent of 0.83, but only three prey sizes were included); (iii) a hump-shaped
      relationship between instantaneous search coefficients and predator-prey body
      mass ratios; and (iv) low scaling exponents for low predator-prey body mass
      ratios in contrast to high scaling exponents for high predator-prey body-mass
      ratios. 4. These scaling relationships suggest that nonlinear interaction
      strengths can be predicted by knowledge of predator and prey body masses. Our
      results imply that predators of intermediate size impose stronger per capita top
      down interaction strengths on a prey than smaller or larger predators. Moreover,
      the stability of population and food-web dynamics should increase with increasing
      body-mass ratios in consequence of increases in the scaling exponents. 5.
      Integrating these scaling relationships into population models will allow
      predicting energy fluxes, food-web structures and the distribution of interaction
      strengths across food web links based on knowledge of the species' body masses.

PMID- 19845812
TI  - Maternal investment and size-specific reproductive output in carcharhinid sharks.
AB  - 1. Life-history theory predicts that organisms will provide an optimal level of
      parental investment for offspring survival balanced against the effects on their
      own survival and future reproductive potential. 2. Optimal resource allocation
      models also predict an increase in reproductive output with age as expected
      future reproductive effort decreases. To date, maternal investment in sharks has
      received limited attention. 3. We found that neonatal dusky sharks (Carcharhinus
      obscurus) are not independent from maternal resource allocation at the point of
      parturition but instead are provisioned with energy reserves in the form of an
      enlarged liver that constitutes approximately 20% of total body mass. 4. Analysis
      of long-term archived data sets showed that a large proportion of this enlarged
      liver is utilized during the first weeks or months of life suggesting that the
      reported weight loss of newborn sharks signifies a natural orientation process
      and is not necessarily related to prey abundance and/or indicative of high
      mortality rates. 5. Interrogation of near-term pup mass in two carcharhinids, the
      dusky and spinner shark (Carcharhinus brevipinna), further revealed an increase
      in reproductive output with maternal size, with evidence for a moderate decline
      in the largest mothers. 6. For the dusky shark, there was a trade-off between
      increasing litter size and near-term pup mass in support of optimal offspring
      size theory. 7. For both the dusky and spinner shark, there was a linear increase
      in near-term pup mass with month, which may indicate variable parturition
      strategies and/or that carcharhinids are able to adjust the length of the
      gestation period. 8. The identification of optimal size-specific reproductive
      output has direct implications for improving the reproductive potential of
      exploited shark populations and for structuring future management strategies.

PMID- 19845813
TI  - Recurrent Torsade de Pointes during mild hypothermia therapy for a survivor of
      sudden cardiac arrest due to drug-induced long-QT syndrome.

PMID- 19845814
TI  - Identification of hemodynamically unstable arrhythmias using subcutaneous
      photoplethysmography.
AB  - INTRODUCTION: Determination of hemodynamic status is central to arrhythmia
      management in the inpatient setting. In contrast, therapy decisions in
      implantable cardioverter defibrillators (ICDs) are based exclusively on the
      arrhythmia's electrical signature. Hemodynamic sensing in ICDs would allow
      tailoring of therapy according to perfusion status. Subcutaneous
      photoplethysmography (PPG) is an attractive technology for this application
      because it responds to changes in arterial pressure and can be readily
      incorporated into the housing of implanted devices. This study evaluated the
      accuracy of PPG in identifying hemodynamically unstable simulated arrhythmias in
      an animal model. METHODS AND RESULTS: Rapid atrial and ventricular pacing was
      used to simulate arrhythmias in an acute preparation of 7 healthy dogs. Aortic
      pressure and subcutaneous PPG were simultaneously recorded. Simulated arrhythmias
      were defined as hemodynamically unstable if aortic pressure decreased by >or=15
      mmHg, marginally unstable if pressure decreased by 5-15 mmHg, and hemodynamically
      stable if pressure either increased or decreased by no more than 5 mmHg. An
      average of 56 arrhythmias were simulated in each animal. Changes in pressure and
      PPG output were highly correlated, with correlation coefficient of 0.7-0.9.
      Subcutaneous PPG identified hemodynamically unstable episodes with a sensitivity
      of 100% for 6 subjects and 80% for 1 subject. Specificity was more than 90% for 6
      subjects and was 50% for 1 subject. CONCLUSIONS: Subcutaneous PPG detects
      hemodynamically unstable simulated arrhythmias in an acute canine preparation. If
      successfully validated in humans, this technology may allow ICD therapy to be
      specifically tailored according to the hemodynamic status of the arrhythmia.

PMID- 19845815
TI  - Limited response to cardiac resynchronization therapy in patients with
      concomitant right ventricular dysfunction.
AB  - INTRODUCTION: Patients with left ventricular dysfunction (LVD) and LV
      dyssynchrony may respond to cardiac resynchronization therapy (CRT). However,
      right ventricular dysfunction (RVD) is a predictor of decreased survival in
      patients with LVD, and its influence on clinical response to CRT is unknown. The
      purpose of this study was to examine the effect of RVD on the clinical response
      to CRT. METHODS AND RESULTS: A retrospective cohort of consecutive patients who
      underwent implantation of a CRT implantable cardioverter-defibrillator (ICD) were
      included and deemed to have RVD based on a RV ejection fraction <0.40. A lack of
      response to CRT was defined as: death, heart transplantation, implantation of an
      LV assist device, absent improvement in NYHA functional class at 6 months or
      hospice care. Among 130 patients included (mean age 58 +/- 11 years, 68.5% male,
      87.7% Caucasian, 51.5% nonischemic cardiomyopathy), 77 (59.2%) had no response to
      CRT as defined above. Of the nonresponders, 43 (56%) had RVD and 34 (44%) did not
      have RVD (P = 0.02). After adjustment for age, race, gender, cardiomyopathy type,
      atrial fibrillation, serum sodium, and severe mitral regurgitation, RVD (adjusted
      OR = 0.34, 95%CI 0.14-0.82), female gender (adjusted OR = 0.36, 95%CI 0.14-0.95),
      and serum creatinine (adjusted OR = 0.25, 95%CI 0.09-0.71) were independently
      associated with decreased odds of response to CRT. There was a significant
      difference in survival of patients with and without RVD after CRT (log rank P =
      0.01). CONCLUSION: RVD represents a strong predictor of lack of clinical response
      to CRT in patients with CHF due to LVD and should be considered when prescribing
      CRT.

PMID- 19845816
TI  - Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel.
AB  - A prerequisite for a normal cardiac function is a proper generation and
      propagation of electrical impulses. Contraction of the heart is obtained through
      a delicate matched transmission of the electrical impulses. A pivotal element of
      the impulse propagation is the depolarizing sodium current, responsible for the
      initial depolarization of the cardiomyocytes. Recent research has shown that
      mutations in the SCN5A gene, encoding the cardiac sodium channel Nav1.5, are
      associated with both rare forms of ventricular arrhythmia, as well as the most
      frequent form of arrhythmia, atrial fibrillation (AF). In this comprehensive
      review, we describe the functional role of Nav1.5 and its associated proteins in
      propagation and depolarization both in a normal- and in a pathophysiological
      setting. Furthermore, several of the arrhythmogenic diseases, such as long-QT
      syndrome, Brugada syndrome, and AF, reported to be associated with mutations in
      SCN5A, are thoroughly described.

PMID- 19845817
TI  - Metabolic profiling reveals key metabolic features of renal cell carcinoma.
AB  - Recent evidence suggests that metabolic changes play a pivotal role in the
      biology of cancer and in particular renal cell carcinoma (RCC). Here, a global
      metabolite profiling approach was applied to characterize the metabolite pool of
      RCC and normal renal tissue. Advanced decision tree models were applied to
      characterize the metabolic signature of RCC and to explore features of
      metastasized tumours. The findings were validated in a second independent
      dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol
      phosphate metabolism determined the metabolic profile of RCC. alpha-tocopherol,
      hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate
      contributed most to the tumour/normal discrimination and all showed pronounced
      concentration changes in RCC. The identified metabolic profile was characterized
      by a low recognition error of only 5% for tumour versus normal samples. Data on
      metastasized tumours suggested a key role for metabolic pathways involving
      arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid
      cycle. These results illustrate the potential of mass spectroscopy based
      metabolomics in conjunction with sophisticated data analysis methods to uncover
      the metabolic phenotype of cancer. Differentially regulated metabolites, such as
      vitamin E compounds, hippuric acid and myoinositol, provide leads for the
      characterization of novel pathways in RCC.

PMID- 19845818
TI  - The normative development of emotion regulation strategy use in children and
      adolescents: a 2-year follow-up study.
AB  - BACKGROUND: Emotion regulation involves intrinsic and extrinsic processes
      responsible for managing one's emotions toward goal accomplishment. Research on
      emotion regulation has predominantly focused on early developmental periods and
      the majority of emotion regulation research examining the pre-adult years has
      lacked a comprehensive theoretical framework. The current study examined the use
      of two strategies of emotion regulation during childhood and adolescents, as
      conceptualised within Gross's (1998) process-oriented model. METHODS: To
      determine the use, norms and development of the Expressive Suppression and
      Cognitive Reappraisal strategies, the Emotion Regulation Questionnaire for
      Children and Adolescents (ERQ-CA) was administered to 1,128 participants aged
      between 9 and 15 years. Three data collection phases, each one year apart,
      enabled investigation of developmental patterns in the use of the two strategies.
      RESULTS: As predicted, Suppression use was found to be lower for older
      participants compared to their younger peers, and over time participants reported
      less use of this strategy. Older participants also scored lower on Reappraisal
      but stability over time was found. Also as expected, males reported more
      Suppression use compared to females. CONCLUSIONS: By documenting the development
      and norms for Cognitive Reappraisal and Expressive Suppression in a community
      sample of children and adolescents, the current study makes a significant
      contribution to our understanding of these two ER strategies during these
      developmental periods.

PMID- 19845819
TI  - Basic measures and systemic medical treatment of patients with toxic epidermal
      necrolysis.
AB  - BACKGROUND: With an incidence of 1.5-1.8/1 million inhabitants per year, toxic
      epidermal necrolysis is a rare but life threatening disease. It is almost always
      drug-induced and its lethality is pronounced with up to 50 %. Several therapeutic
      options are described in literature; however, there is still lack of a
      universally accepted and specific therapy of toxic epidermal necrolysis. METHODS:
      This survey considers 8 cases of toxic epidermal necrolysis diagnosed and treated
      in our clinic from 2003 to 2007. The epidermal sloughing was > 30 % of the body
      surface in each case. RESULTS: After immediately discontinuing the drug suspected
      of being responsible for toxic epidermal necrolysis, we treated with systemic
      corticosteroids in an initial dose of up to 1.5 mg/kg. Moreover, special emphasis
      was put on basic measures such as control of vital parameters. With this
      treatment we reached good results; none of the patients died. conclusions:
      Immediate beginning of therapy is essential for a successful treatment of toxic
      epidermal necrolysis. Besides systemic therapy with corticosteroids, certain
      basic measures such as isolation of patients at adequate room temperature to
      prevent hypothermia, strict control of circulation, temperature and laboratory
      parameters, daily smears of skin and mucous membranes and a diet rich in calories
      due to the catabolic metabolic status are very important for successful outcome.

PMID- 19845820
TI  - Successful treatment of cheilitis granulomatosa with intralesional injection of
      triamcinolone.

PMID- 19845821
TI  - Internet-supported gathering of treatment data and patient benefits in psoriasis.
AB  - BACKGROUND: Studies about health care of psoriasis patients in Germany are
      predominantly carried out in dermatological centres, which results in a certain
      selection bias. To collect data from other sources of patients, the German Centre
      of Health Services Research in Dermatology conducted a series of web-based
      studies. The extent of how data on health care on psoriasis gathered online vary
      from paper and pencil data is yet to be explored. OBJECTIVE: 1 To collect
      reliable treatment and benefit online data from psoriasis patients in Germany. 2
      To compare these with data gathered at dermatological centres. METHODS: On the
      'psoriasis-hilfe.de' web portal, psoriasis patients were asked to complete the
      online version of a questionnaire, which has already been used as a paper and
      pencil version in the national psoriasis study 'PsoHealth'. Subsequently,
      difference analyses were conducted between the two data sets. RESULTS: The PsoWeb
      sample (n = 1071) varies to a high extent from the PsoHealth sample (n = 2009)
      regarding the achievement of treatment goals and treatment satisfaction.
      Irrespective of age, sex and duration of disease, the online sample showed lower
      treatment satisfaction and fewer patient-defined benefits. CONCLUSION: The
      findings suggest that patients in the online sample are less satisfied with their
      health care, which also could have been their motive for participating online. It
      is important to gather data online because it increases the data pool and permits
      inclusion of people who are not incorporated in clinical settings. However,
      online data cannot directly replace data collected in clinics because they are
      also subject to selections.

PMID- 19845822
TI  - Treatment of scalp psoriasis with clobetasol-17 propionate 0.05% shampoo: a study
      on daily clinical practice.
AB  - BACKGROUND: Safety and clinical effectiveness of clobetasol-17 propionate 0.05%
      shampoo have been shown in patients with scalp psoriasis. AIM: First, to evaluate
      treatment satisfaction, user convenience safety and effectiveness of clobetasol
      17 propionate 0.05% shampoo treatment in daily clinical practice. Second, to
      identify subgroup variables that may predict treatment success or failure.
      METHODS: A total of 56 patients with scalp psoriasis were treated with short
      contact clobetasol-17 propionate 0.05% shampoo once daily for 4 weeks. Data on
      treatment satisfaction, user convenience, safety and effectiveness were assessed
      on a 7-point Likert scale using postal questionnaires. Subgroup analyses were
      performed to identify variables that may predict treatment outcome. RESULTS: A
      total of 41 patients returned both questionnaires (73%). Positive treatment
      satisfaction and user convenience were reported by 66% and 79% of patients
      respectively. Patient-rated indicators for disease severity improved by 39-46% (P
      < 0.05%). No major side-effects were reported. Subgroup analyses did not reveal
      any statistically significant patient variable that may predict treatment
      outcome. However, a tendency towards improved treatment satisfaction was observed
      in patients who had received fewer topical antipsoriatic treatments previously (P
      > 0.05). CONCLUSIONS: Short-contact treatment with clobetasol-17 propionate 0.05%
      shampoo has high user convenience and patient satisfaction rates. Moreover, the
      treatment is well-tolerated and efficacious from patients' perspective. Subgroup
      analyses did not reveal factors predicting treatment outcome, although treatment
      success tended to be more evident in patients who had received fewer treatments
      previously.

PMID- 19845823
TI  - Ascitic fluid infection in patients with hepatitis B virus-related liver
      cirrhosis: culture-negative neutrocytic ascites versus spontaneous bacterial
      peritonitis.
AB  - BACKGROUND AND AIM: Ascitic fluid infection (AFI) consists of culture-negative
      neutrocytic ascites (CNNA) and spontaneous bacterial peritonitis (SBP). The
      present study compared the clinical characteristics and prognosis of CNNA and SBP
      in hepatitis B virus (HBV)-related cirrhotic patients. METHODS: We analyzed 130
      consecutive patients hospitalized due to the first episode of AFI between January
      1998 and December 2007. RESULTS: The mean age of the patients was 52.3 years (88
      men, 42 women). Ninety-three patients (71.5%) had CNNA and 37 patients (28.5%)
      had SBP; 117 patients (90.0%) died after a median survival period of 6.4 months.
      Patients with CNNA and SBP survived for a median period of 6.9 months and 5.4
      months, respectively (P = 0.417). Patients with SBP showed higher in-hospital
      mortality than those with CNNA (16.2 vs 4.3%; P = 0.031). Binary logistic
      regression analysis showed that culture positivity of ascitic fluid (CNNA vs SBP)
      was the only independent predictor of in-hospital mortality (P = 0.042). In a Cox
      regression model for the 120 patients (92.3%) who survived the first episode of
      AFI, only the Child-Pugh score remained significant for survival (P = 0.007),
      whereas no association was observed for culture positivity of ascitic fluid (CNNA
      vs SBP) during the first episode of AFI (P = 0.752). CONCLUSIONS: Although in
      hospital mortality was higher in patients with SBP than CNNA, the clinical course
      of the two groups was similar after the first episode of AFI. Thus, liver
      transplantation should be considered, irrespective of culture positivity of
      ascitic fluid.

PMID- 19845824
TI  - Role of endoscopic ultrasound-guided fine-needle aspiration with flow cytometry
      to diagnose lymphoma: a single center experience.
AB  - BACKGROUND AND AIM: The use of endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) +/- flow cytometry (FC) for the diagnosis of suspected
      lymphoma remains controversial. We report our experience and diagnostic yield for
      EUS +/- FC for suspected lymphoma. METHODS: Databases were queried for those who
      underwent EUS-FNA +/- FC for suspected lymphoma. Hospital charts were reviewed to
      confirm the final cytological diagnosis, follow up and FC results if obtained.
      The final diagnosis was confirmed by the results of EUS-FNA +/- FC, other biopsy
      and/or follow up. RESULTS: In total, 54 patients underwent EUS-FNA of 72 lesions.
      The final diagnosis of lymphoma was made in 38 of the 54 (70%) patients, and 33
      of the 54 (61%) patients relied on EUS-FNA. Cytopathology in 41 patients using
      EUS-FNA + FC showed lymphoma in 24 patients, atypical lymphoid cells in six and
      reactive lymph node in 11. In 9 of the 24 with lymphoma by EUS + FC, the
      diagnosis was confirmed by another diagnostic modality, like surgery, bone marrow
      biopsy and computed tomography-guided biopsy. Of the six with atypical lymphoid
      cells, additional diagnostic methods confirmed lymphoma in three. The remaining
      13 of the 54 patients underwent EUS-FNA without FC due to insufficient sample (n
      = 5) or operator choice (n = 8). Cytopathology in these 13 patients without FC
      showed lymphoma (9), atypical lymphoid cells (3) and reactive node (1). The
      sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy of EUS-FNA for lymphoma in all 54 patients ranged from 80% to 87%,
      92% to 93%, 97%, 60% to 75% and 83% to 89%, respectively. CONCLUSIONS: EUS-FNA is
      sensitive and specific for the diagnosis of suspected lymphoma. Confirmatory or
      further testing should be performed when EUS-FNA with or without FC is
      indeterminate and or non-diagnostic.

PMID- 19845825
TI  - Vitamin D status and optimal supplementation in institutionalized adults with
      intellectual disability.
AB  - BACKGROUND: Adults with intellectual disability (ID) have several risk factors
      for osteoporosis. Feeding problems with consequent nutritive deficiencies, and
      lack of sunshine exposure may lead to vitamin D deficiency. The purpose of this
      study was to evaluate vitamin D status in adults with ID living in nursing homes
      and to compare two different means to administer vitamin D in adults with ID.
      METHODS: The study included 138 adults (95 males and 43 females) with ID living
      in nursing homes of Paajarvi Inter-Municipal Association. Clinical data on the
      etiology and severity of ID, other illnesses, medications, anthropometry and
      fractures during the preceding 5 years were collected from medical records. The
      participants were alternately allocated to receive vitamin D3 either per orally
      800 IU daily for 6 months (PO group, n = 72) or as a single intramuscular
      injection of 150 000 IU (IM group, n = 66). Blood samples were obtained at
      baseline and at 6 months for parameters of calcium homeostasis, including serum
      concentrations of 25-hydroxyvitamin D (S-25-OHD) and parathyroid hormone (P-PTH).
      RESULTS: At baseline, the mean S-25-OHD was low, 40 nmol/L in the PO group and 41
      nmol/L in the IM group. The low vitamin D levels were associated with secondary
      hyperparathyroidism in 17%. At 6 months the mean S-25-OHD was 82 nmol/L in the PO
      group (P < 0.001 for the difference from baseline) and 62 nmol/L in the IM group
      (P < 0.001). P-PTH decreased in both groups: from 51 ng/L to 33 ng/L in the PO
      group (P < 0.001) and from 54 ng/L to 34 ng/L in the IM group (P < 0.001). With
      daily dosing (800 IU/day) the recommended level (>80 nmol/L) was attained in 42%,
      but with intramuscular dose only in 12%. S-25-OHD was >100 nmol/L in 14
      participants in the PO group and in one participant in the IM group; these high
      values were associated with hypercalcemia in two and hyperphosphatemia in six
      participants. Participants with S-25-OHD >100 nmol/L at 6 months were lighter
      (51.9 kg vs. 67.5 kg, P = 0.002) and had smaller body mass index than
      participants with lower S-25-OHD (20.5 kg/m(2) and 24.4 kg/m(2), P = 0.017).
      CONCLUSIONS: Vitamin D insufficiency was common in adults with ID living in
      nursing homes. Both oral and intramuscular administrations of vitamin D3 improved
      vitamin D status without adverse effects. The treatment response at 6 months was
      better in the PO group. High-dose intramuscular vitamin D3 injections may be a
      convenient way to maintain sufficient vitamin D status in adults with ID but
      further studies are needed to establish the optimal dose and interval as well as
      subsequent potential health benefits in these patients. Based on this study,
      vitamin D supplementation with per oral 800 IU/day is recommended to all adults
      with ID living in nursing homes.

PMID- 19845826
TI  - Coping strategy use, personality, and adjustment of parents rearing children with
      developmental disabilities.
AB  - BACKGROUND: Parents rearing children with developmental disabilities encounter
      stressors that require coping and adaptation. In Glidden et al. 2006, the use of
      problem-focused coping strategies was more often associated with positive
      adjustment outcomes than was the use of emotion-focused coping strategies, and
      parental personality was shown to influence outcomes, with Neuroticism, in
      particular, associated with lower well-being. METHOD: In the current study we
      aimed to replicate these results for adjustment outcomes measured 6 years later.
      Sixty-eight married couples parenting at least one child with developmental
      disabilities completed measures of depression and subjective well-being, and the
      Transition Daily Rewards and Worries Questionnaire, an inventory that assesses
      parental reaction to children transitioning into adulthood. RESULTS: For both
      mothers and fathers, combinations of personality factors and coping strategies
      were able to significantly predict outcome variables measured 6 years later.
      Personality, however, was a better predictor for mothers, whereas coping
      strategies predicted more variance for fathers. Distancing, especially,
      demonstrated mother-father differences. CONCLUSIONS: For the most part, the
      current results demonstrated that the relations among personality, coping and
      parental outcomes were consistent and stable over the 6-year interval. In
      addition, although we found some differences between mothers and fathers, there
      were also many similarities in the frequency of use of different coping
      strategies, and in the direction of influence of personality and coping strategy
      on outcome variables.

PMID- 19845827
TI  - Hypoxia-inducible factor 1: a new hope to counteract neurodegeneration?
AB  - Neurodegenerative diseases, generally characterized by a progressive
      deterioration in the structure and function of the brain, represent one of the
      world's major unsolved health problems. Therefore, it is urgent to discover
      therapeutic targets for the design of effective strategies for the treatment of
      these diseases. Recent findings demonstrated that the induction of the hypoxia
      signaling pathway with the concomitant stabilization and transcriptional
      activation of the transcription factor hypoxia-inducible factor 1 (HIF-1) could
      mediate neuroprotective events. It has been shown that HIF-1 triggers the
      expression of genes involved in oxygen transport, glycolytic metabolism,
      angiogenesis, cell survival, apoptosis, and others processes that can interfere
      with cell survival. Here, we discuss the current knowledge pertaining to the
      regulation of HIF signaling pathway. The potential neuroprotective role of HIF-1
      induction in cerebral ischemic stroke and Alzheimer's, Parkinson's, and
      Huntington's diseases will be also discussed. The elucidation of the mechanisms
      involved in HIF-1-mediated neuroprotection could be important for the development
      of effective therapies to mitigate or prevent neurodegenerative diseases.

PMID- 19845828
TI  - Blood levels of kynurenines, interleukin-23 and soluble human leucocyte antigen-G
      at different stages of Huntington's disease.
AB  - There is substantial evidence that abnormal concentrations of oxidised tryptophan
      metabolites, produced via the kynurenine pathway, contribute to progressive
      neurodegeneration in Huntington's disease. We have now examined the blood levels
      of these metabolites in patients at different stages of Huntington's disease,
      assessed both in terms of clinical disease severity and numbers of CAG repeats.
      Close relatives of the patients were included in the study as well as unrelated
      healthy controls. Levels of lipid peroxidation products, the pro-inflammatory
      cytokine interleukin (IL)-23 and the soluble human leucocyte antigen-G (sHLA-G)
      were also measured. There were lower levels of tryptophan and a higher kynurenine
      : tryptophan ratio, indicating activation of indoleamine-2,3-dioxygenase, in the
      most severely affected group of patients, with increased levels of IL-23 and sHLA
      G. Marked correlations were noted between IL-23 and the patient severity group,
      anthranilic acid levels and the number of CAG repeats, and between anthranilic
      acid and IL-23, supporting our previous evidence of a relationship between
      anthranilic acid and inflammatory status. Tryptophan was negatively correlated
      with symptom severity and number of CAG repeats, and positively correlated with
      sHLA-G. The results support the proposal that tryptophan metabolism along the
      kynurenine pathway in Huntington's disease is related to the degree of genetic
      abnormality, to clinical disease severity and to aspects of immunopathogenesis.

PMID- 19845829
TI  - Inactivation of cytochrome c oxidase by mutant SOD1s in mouse motoneuronal NSC-34
      cells is independent from copper availability but is because of nitric oxide.
AB  - The copper-enzyme cytochrome c oxidase (Cytox) has been indicated as a primary
      molecular target of mutant copper, zinc superoxide dismutase (SOD1) in familial
      amyotrophic lateral sclerosis (fALS); however, the mechanism underlying its
      inactivation is still unclear. As the toxicity of mutant SOD1s could arise from
      their selective recruitment to mitochondria, it is conceivable that they might
      compete with Cytox for the mitochondrial copper pool causing Cytox inactivation.
      To investigate this issue, we used mouse motoneuronal neuroblastoma x spinal cord
      cell line-34, stably transfected for the inducible expression of low amounts of
      wild-type or mutant (G93A, H46R, and H80R) human SOD1s and compared the effects
      observed on Cytox with those obtained by copper depletion. We demonstrated that
      all mutants analyzed induced cell death and decreased the Cytox activity, but not
      the protein content of the Cytox subunit II, at difference with copper depletion
      that also affected subunit II protein. Copper supplementation did not counteract
      mutant hSOD1s toxicity. Otherwise, the treatment of neuroblastoma x spinal cord
      cell line-34 expressing G93A, H46R, or H80R hSOD1 mutants, and showing
      constitutive expression of iNOS and nNOS, with either a NO scavenger, or NOS
      inhibitors prevented the inhibition of Cytox activity and rescued cell viability.
      These results support the involvement of NO in mutant SOD1s-induced Cytox damage,
      and mitochondrial toxicity.

PMID- 19845830
TI  - Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption
      and accumulation of cholesteryl esters in the brain.
AB  - Cathepsin D (CTSD) deficiencies are fatal neurological diseases that in human
      infants and in sheep are characterized by extreme loss of neurons and myelin. To
      date, similar morphological evidence for myelin disruption in CTSD knockout mice
      has not been reported. Here, we show that CTSD deficiency leads to pronounced
      myelin changes in the murine brain: myelin-related proteolipid protein and myelin
      basic protein were both markedly reduced at postnatal day 24, and the amount of
      lipids characteristically high in myelin (e.g. plasmalogen-derived alkenyl chains
      and glycosphingolipid-derived 20- and 24-carbon acyl chains) were significantly
      lowered compared with controls. These changes were accompanied by ultrastructural
      alterations of myelin, including significant thinning of myelin sheaths.
      Furthermore, in CTSD knockout brains there was a pronounced accumulation of
      cholesteryl esters and abnormal levels of proteins related to cholesterol
      transport, with an increased content of apolipoprotein E and a reduced content of
      ATP-binding cassette transporter A1. These results provide evidence for
      dysmyelination and altered trafficking of cholesterol in brains of CTSD knockout
      mice, and warrant further studies on the role of lipid metabolism in the
      pathogenesis of CTSD deficiencies.

PMID- 19845831
TI  - ACh receptors link two signaling pathways to neuroprotection against glutamate
      induced excitotoxicity in isolated RGCs.
AB  - Previous studies have reported that activation of nicotinic acetylcholine (ACh)
      receptors (nAChRs) on cultured pig retinal ganglion cells (RGCs) has a
      neuroprotective effect against glutamate-induced excitotoxicity. However, the
      mechanism linking nAChRs to neuroprotection is unknown. Here, we tested the
      hypothesis that signaling cascades involving p38 mitogen-activated protein kinase
      (MAPK) and phosphatidylinositol 3-kinase (PI3K) --> Akt are involved in linking
      activation of nAChRs to neuroprotection in isolated pig RGCs. In ELISA studies,
      regulation of phosphorylated p38 MAPK and Akt were analyzed after inducing
      excitotoxicity or neuroprotection in the presence and absence of specific
      inhibitors for p38 MAPK and PI3K. ELISA results demonstrated that ACh
      significantly increased phosphorylated Akt and decreased p38 MAPK. Glutamate
      increased phosphorylated p38 MAPK but had no significant effect on phosphorylated
      Akt. Other ELISA studies using p38 MAPK and PI3K inhibitors also supported the
      hypothesis that ACh up-regulated Bcl-2 levels downstream from PI3K and Akt,
      whereas glutamate down-regulated Bcl-2 levels downstream from p38 MAPK. RGC
      survival was subsequently assessed by culturing RGCs in conditions to induce
      excitotoxicity or neuroprotection in the presence or absence of specific
      inhibitors of p38 MAPK or PI3K. The p38 MAPK inhibitor significantly decreased
      the number of RGCs that died by glutamate-induced excitotoxicity but had no
      effect on the number of cells that survived because of ACh-induced
      neuroprotection. PI3K inhibitors significantly decreased cell survival caused by
      ACh-induced neuroprotection but had no effect on cell death caused by glutamate
      induced excitotoxicity. These results demonstrate that glutamate mediates
      excitotoxicity through the p38 MAPK signaling pathway and that ACh provides
      neuroprotection by stimulating the PI3K --> Akt --> Bcl-2 signaling pathway and
      inhibiting the p38 MAPK --> Bcl-2 pathway.

PMID- 19845832
TI  - The TRPC6 channel activator hyperforin induces the release of zinc and calcium
      from mitochondria.
AB  - Hyperforin, an extract of the medicinal plant hypericum perforatum (also named St
      John's wort), possesses antidepressant properties. Recent data showed that it
      elevates the intracellular concentration of Ca(2+) by activating diacylglycerol
      sensitive C-class of transient receptor potential (TRPC6) channels without
      activating the other isoforms (TRPC1, TRPC3, TRPC4, TRPC5, and TRPC7). This study
      was undertaken to further characterize the cellular neuronal responses induced by
      hyperforin. Experiments conducted on cortical neurons in primary culture and
      loaded with fluorescent probes for Ca(2+) (Fluo-4) and Zn(2+) (FluoZin-3) showed
      that it not only controls the activity of plasma membrane channels but it also
      mobilizes these two cations from internal pools. Experiments conducted on
      isolated brain mitochondria indicated that hyperforin, like the inhibitor of
      oxidative phosphorylation, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone
      (FCCP), collapses the mitochondrial membrane potential. Furthermore, it promotes
      the release of Ca(2+) and Zn(2+) from these organelles via a ruthenium red
      sensitive transporter. In fact, hyperforin exerts complex actions on CNS neurons.
      This antidepressant not only triggers the entry of cations via plasma membrane
      TRPC6 channels but it displays protonophore-like properties. As hyperforin is now
      use to probe the functions of native TRPC6 channels, our data indicate that
      caution is required when interpreting results obtained with this antidepressant.

PMID- 19845833
TI  - Disease-toxicant screen reveals a neuroprotective interaction between
      Huntington's disease and manganese exposure.
AB  - Recognizing the similarities between Huntington's disease (HD) pathophysiology
      and the neurotoxicology of various metals, we hypothesized that they may exhibit
      disease-toxicant interactions revealing cellular pathways underlying
      neurodegeneration. Here, we utilize metals and the STHdh mouse striatal cell line
      model of HD to perform a gene-environment interaction screen. We report that
      striatal cells expressing mutant Huntingtin exhibit elevated sensitivity to
      cadmium toxicity and resistance to manganese toxicity. This neuroprotective gene
      environment interaction with manganese is highly specific, as it does not occur
      with iron, copper, zinc, cobalt, cadmium, lead, or nickel ions. Analysis of the
      Akt cell stress signaling pathway showed diminished activation with manganese
      exposure and elevated activation after cadmium exposure in the mutant cells.
      Direct examination of intracellular manganese levels found that mutant cells have
      a significant impairment in manganese accumulation. Furthermore, YAC128Q mice, a
      HD model, showed decreased total striatal manganese levels following manganese
      exposure relative to wild-type mice. Thus, this disease-toxicant interaction
      screen has revealed that expression of mutant Huntingtin results in heightened
      sensitivity to cadmium neurotoxicity and a selective impairment of manganese
      accumulation.

PMID- 19845834
TI  - Sex differences in the expression of sex steroid receptor mRNA in the quail
      brain.
AB  - In Japanese quail, males will readily exhibit the full sequence of male-typical
      sexual behaviors but females never show this response, even after ovariectomy and
      treatment with male-typical concentrations of exogenous testosterone.
      Testosterone aromatisation plays a key-limiting role in the activation of this
      behavior but the higher aromatase activity in the brain of males compared to
      females is not sufficient to explain the behavioural sex difference. The cellular
      and molecular bases of this prominent sex difference in the functional
      consequences of testosterone have not been identified so far. We hypothesised
      that the differential expression of sex steroid receptors in specific brain areas
      could mediate this behavioural sex difference. Therefore, using radioactive in
      situ hybridisation histochemistry, we quantified the expression of the mRNA
      coding for the androgen receptor (AR) and the oestrogen receptors (ER) of the
      alpha and beta subtypes. All three receptors were expressed in an anatomically
      discrete manner in various nuclei of the hypothalamus and limbic system and, at
      usually lower densities, in a few other brain areas. In both sexes, the intensity
      of the hybridisation signal for all steroid receptors was highest in the medial
      preoptic nucleus (POM), a major site of testosterone action that is related to
      the activation of male sexual behaviour. Although no sex difference in the
      optical density of the AR hybridisation signal could be found in POM, the area
      covered by AR mRNA was significantly larger in males than in females, indicating
      a higher overall degree of AR expression in this region in males. By contrast,
      females tended to have significantly higher levels of AR expression than males in
      the lateral septum. ERalpha was more densely expressed in females than males
      throughout the medial preoptic and hypothalamic areas (including the POM and the
      medio-basal hypothalamus), an area implicated in the control of female
      receptivity) and in the mesencephalic nucleus intercollicularis. ERbeta was more
      densely expressed in the medio-basal hypothalamus of females but a difference in
      the reverse direction (males > females) was observed in the nucleus taeniae of
      the amygdala. These data suggest that a differential expression of steroid
      receptors in specific brain areas could mediate at least certain aspects of the
      sex differences in behavioural responses to testosterone, although they do not
      appear to be sufficient to explain the complete lack of activation by
      testosterone of male-typical copulatory behaviour in females.

PMID- 19845836
TI  - Daily chewing gum exercise for stabilizing the vertical occlusion.
AB  - We investigated the effects of a chewing gum exercise program on occlusal
      conditions and evaluated compliance of subjects. Thirty-five healthy adult
      volunteers (26 males and nine females) were asked to chew gum for 10-15 min
      before or after three meals daily for four weeks. Occlusal conditions were
      recorded as occlusal parameters, such as occlusal contact area, occlusal contact
      force, and pressure using dental prescale films. These parameters were evaluated
      by an Occluzer before the exercise period commenced, after four weeks of
      exercise, and then one month after the end of the exercise period. These
      parameters were statistically compared using one-way ANOVA. We found that: (i)
      after four weeks of exercise, anterior and posterior occlusal contact areas and
      forces were significantly (P < 0.05) increased and the increments were
      significantly (P < 0.05) higher in the anterior occlusal contact area and force
      than in the posterior occlusal contact area and force, (ii) the anteroposterior
      ratio of occlusal contact area and force increased, but not markedly, (iii)
      increased parameters had significantly (P < 0.05) decreased within one month
      after the end of the four-week exercise period, (iv) most participants did not
      complain for discomfort or stress during the exercise. The chewing gum exercise
      program could increase occlusal contact area and force and also move the
      anteroposterior occlusal balance forward. Patient compliance with the exercise is
      likely high enough to keep them exercising.

PMID- 19845835
TI  - Possible involvement of microglia containing cyclooxygenase-1 in the accumulation
      of gonadotrophin-releasing hormone in the preoptic area in female rats.
AB  - Prostaglandins (PGs), especially PGE(2), are involved in the hypothalamic control
      of gonadotrophin-releasing hormone (GnRH) release, acting at least in part on the
      terminal of GnRH axons in the median eminence. The present study aimed: (i) to
      clarify the role of PG(s) in regulating GnRH cell function at the level of the
      perikarya in the preoptic area; (ii) to determine the cyclooxygenase (COX)
      isozyme responsible for producing PG(s) that regulates GnRH perikarya; and (iii)
      to identify cell types that contain the responsible COX isozyme in female rats. A
      surge of luteinising hormone (LH) secretion was induced by oestrogen and
      progesterone in ovariectomised rats. Treatment of the rat before the LH surge
      with indomethacin, a nonselective COX inhibitor, or NS-398, a selective COX-2
      inhibitor, did not interfere with the surge. However, treatment with indomethacin
      or flurbiprofen, a selective COX-1 inhibitor, significantly reduced the number of
      GnRH-immunoreactive cells in the preoptic area at the time of peak LH secretion
      during the surge. NS-398 did not affect the GnRH immunoreactivity. Double
      labelled immunofluorescent histochemistry revealed COX-1 immunoreactivity in the
      vicinity of, but not within, GnRH containing neurones in the preoptic area. COX-2
      immunoreactivity was not found in the same area. The COX-1 immunoreactivity was
      almost entirely localised in microglia in the preoptic area, but not in neurones
      or astrocytes. These results suggest that microglia in the preoptic area
      containing COX-1 are responsible for producing PG(s), which, in turn, facilitates
      the accumulation of GnRH during the gonadotrophin surge in female rats.

PMID- 19845837
TI  - Ursodeoxycholic acid's role in avoiding diversionary surgery in idiopathic
      fibrosing pancreatitis.
AB  - Obstructive jaundice in childhood is rare but a cause of great concern and
      warrants aggressive investigation into its aetiology. Idiopathic fibrosing
      pancreatitis (IFP) is a rare cause of this phenomenon and is presently a
      diagnosis of exclusion with lymphoma a main differential diagnosis. IFP appears
      to be a self limiting occurrence and as a result the previous gold standard of
      therapy of surgical diversion may ultimately be unnecessary. We describe
      ursodeoxycholic acid as a useful adjunct to treatment allowing more time for
      clinicians to evaluate the nature of the underlying disease process without
      hastily moving towards invasive surgery until clearly indicated.

PMID- 19845838
TI  - Epidemiology of major paediatric chest trauma.
AB  - AIM: Paediatric chest trauma is a marker of severe injury and a significant cause
      of morbidity and mortality. However, current trends in the Australian population
      are unknown. This study aims to outline the profile and management of major
      paediatric chest trauma in Victoria. METHODS: Prospectively collected data of
      patients from the Victorian State Trauma Registry from July 2001 to June 2007
      were retrospectively reviewed. Data on fatalities were obtained from the National
      Coroners Information System. Descriptive statistics were used to summarise the
      profiles of major trauma cases and coroners' cases. RESULTS: Overall, 204 cases
      with serious paediatric chest injuries were reported by the Victorian State
      Trauma Registry (n = 158) and National Coroners Information System (n = 46)
      (excluding overlapping cases) in 2001-2007. Paediatric chest trauma was more
      common in males. The Injury Severity Score ranged from 16 to 25 in most patients.
      Blunt trauma was responsible for 96% of cases, of which motor vehicle collisions
      accounted for 75%. Median hospitalisation was 9 days, and 64% of patients were
      admitted to intensive care. Common injuries included lung contusion (66%),
      haemo/pneumothorax (32%) and rib fracture (23%). Multiple organ injury occurred
      in 99% of cases, with head (62%) and abdominal (50%) injury common. Management
      was conservative, with only 11 cases (7%) treated surgically. The highest
      mortality was in the 10-15-year age group. In 52 (79%) fatalities, injury was
      transport related. CONCLUSION: Australian paediatric chest trauma trends are
      similar to international patterns. Serious injury requiring surgical intervention
      is rare. This limited exposure may lead to difficulty in maintaining surgical
      expertise in this highly specialised area.

PMID- 19845839
TI  - Socio-cultural perceptions of sudden infant death syndrome among migrant Indian
      mothers.
AB  - AIM: To explore socio-cultural influences on migrant mother decisions and beliefs
      regarding co-sleeping as a risk factor for sudden infant death syndrome (SIDS).
      METHODS: Semi-structured interviews with five Indian-born women in a socio
      economically disadvantaged suburb in the south-west of Sydney were conducted
      between September and December 2007. Transcripts were analysed using principles
      of discourse analysis. RESULTS: Discourse analysis revealed that SIDS-related
      decisions and beliefs about co-sleeping as a risk factor for SIDS are constructed
      amid competing discourses of motherhood and child health. Mothers are either
      actively or unconsciously deciding how they negotiate or resist dominant Western
      discourses of motherhood and child health to make 'the best' health-related
      decisions for their children. Participants resisted acknowledging child sleep
      practices recommended by health practitioners, particularly recommendations to
      put to sleep the baby in its own cot. This resistance was expressed by
      constructing messages as 'inapplicable' and 'inappropriate'. Co-sleeping was
      constructed as a highly valued practice for its physical and social benefits to
      the child, mother and family by facilitating child security, breastfeeding,
      bonding and family connectedness. CONCLUSION: This study illustrates how
      decisions and behaviour are shaped by socio-cultural influences embedded in
      discourses and context. It also shows that in-depth investigation through a
      social constructivist lens is particularly useful for investigating influences on
      knowledge acquisition, interpretation and implementation among migrant groups. A
      greater appreciation of the social meanings and ideologies attached to behaviours
      can help to ensure that the correct messages reach the correct populations, and
      that child health outcomes can be achieved and maintained both for overseas and
      Australian-born populations.

PMID- 19845840
TI  - Children in out-of-home care: does routine health screening improve outcomes?
AB  - AIM: Children in out-of-home care have high and frequently unidentified health
      needs. The Child Protection Unit at Sydney Children's Hospital offers
      comprehensive health screening to children in care. Recommendations for
      remediation are made, but follow-up in the clinic is not offered. Current
      research has failed to establish whether health screening results in health
      benefits for the children screened. The aim of this study was to assess the
      impact of the health screening clinic on children's health outcomes by tracking
      the first 100 children screened, determining how many of the health
      recommendations made for each child had been implemented and, if possible, what
      the health outcome had been. METHODS: Research questionnaires were sent to the
      Department of Social Services caseworkers of the first 100 children screened.
      RESULTS: Adherence to health recommendations was high; however, it was not
      possible to quantify the degree of health benefit to the children screened. A
      number of systemic problems were identified, which are likely to hinder the
      accessibility of health care for children in care. CONCLUSIONS: Comprehensive
      health screening of children in care is likely to benefit a child's health,
      although this could not be determined. Agencies responsible for placing children
      in care need systems in place to ensure better inter-agency collaboration between
      the health system and community services. This should help improve health
      outcomes.

PMID- 19845841
TI  - Influenza-related hospitalisations in children.
AB  - AIM: To describe the disease burden, clinical pattern and outcome of influenza
      related hospitalisations in children. METHODS: This is a retrospective study
      carried out in a regional hospital in Hong Kong. Children hospitalised with
      established diagnosis of influenza infection from January to June of 2005 were
      studied. Length of hospitalisation, demographic characteristics, symptoms,
      clinical diagnosis and complications of influenza infection were analysed.
      RESULTS: Influenza A infection accounted for 93.5% of these hospitalisations.
      Children less than 5 years of age comprised 70% of admission. Highest rate of
      admission occurred in May and April. One fourth of emergency admission during the
      study period and over 70% in the peak season was a result of influenza-related
      illness. Underlying medical disease was observed in 14.6% of children. Mean
      duration of hospitalisation was 3.0 days. Fever was the commonest presenting
      symptoms. Fever lasting for 7 days or more was observed in one-fifth of patients.
      Respiratory tract diseases (upper and lower) were the most frequent non
      neurological diagnosis. Febrile convulsion was the complication observed in 27.6%
      of admission. One patient died as a result of acute necrotising encephalopathy.
      CONCLUSION: Influenza contributed to heavy health-care burden. Mortality was rare
      but did occur. Hospitalisations occurred in both healthy children and those with
      underlying chronic illness. Young children played an important role in such
      hospitalisations. Means to prevent influenza-associated morbidity and mortality
      especially among young children are needed.

PMID- 19845842
TI  - The effects of birthweight and breastfeeding on asthma among children aged 1-5
      years.
AB  - AIM: Asthma is a major cause of morbidity and mortality among children and has
      steadily increased in prevalence. The combined effect of birthweight and
      breastfeeding on childhood asthma remains unclear. METHODS: In this study, we
      analysed a nationally representative sample of children aged 1-5 years from the
      National Health and Nutrition Examination Survey 1999-2002. Logistic regression
      was performed to examine the hypothesis whether birthweight and breastfeeding are
      independently associated with the prevalence of asthma after accounting for the
      complex sampling design. In addition, we sought to describe the relationship
      between birthweight and childhood asthma and to assess the potentially combined
      effect between birthweight and breastfeeding on asthma among children aged 1-5
      years after considering the possible effects of social and environmental factors.
      RESULTS: We found that birthweight (measured continuously) was inversely and
      linearly associated with the prevalence of childhood asthma (odds ratio (OR) =
      0.80 per 1 kg increase in birthweight, 95% confidence interval (CI): 0.65-0.98).
      Using a categorical variable, low birthweight (LBW) was positively associated
      with childhood asthma (OR = 1.28, 95% CI: 0.81-2.68). Furthermore, we detected an
      interaction between birthweight and breastfeeding on childhood asthma.
      Breastfeeding had a strong protective effect on asthma among children with high
      birthweight (OR = 0.14, 95% CI: 0.04-0.43) while it had no significant effect on
      asthma among children with normal birthweight or LBW. CONCLUSIONS: The mechanisms
      underlying these relationships remain uncertain and warrant further explanation.

PMID- 19845843
TI  - Familial Mediterranean fever gene mutations in the inner northern region of
      Turkey and genotype-phenotype correlation in children.
AB  - AIM: Familial Mediterranean fever (FMF) is an autosomal recessive disorder
      characterised by recurrent episodes of fever, polyserositis and rash. The aim of
      this study was to determine the most common mutations and clinical features, and
      their relationships. METHODS: The medical records of 78 patients were evaluated
      retrospectively. All of the patients had been diagnosed with FMF according to Tel
      Hashomer criteria between January 2005 and May 2008 in general paediatric clinics
      of the School of Medicine at Gaziosmanpasa University. Twelve mutations were
      detected in the 78 patients by polymerase chain reaction-enzyme-linked
      immunosorbent assay. The patients were classified into three groups according to
      allele status. RESULTS: The most prominent clinical symptoms were abdominal pain
      (95%), fever (90%), arthritis (33%) and pleuritis (31%). Seventeen different
      genotypes were identified. The mutations were homozygous in 25 (32%) patients,
      compound heterozygous in 28 (36%) patients and heterozygous in 22 (28%) patients.
      No mutation was detected in three (4%) patients. The most frequent mutations were
      M694V (55%), M680I (16%), E148Q (10%) and P369S (4%). The mean symptom severity
      score was highest in the homozygous group, and high levels of C-reactive protein
      were also detected in this group. CONCLUSIONS: In addition to clinical criteria,
      molecular studies for detecting disease-causing mutations are needed to establish
      the diagnosis of FMF. FMF patients who were homozygous for MEFV gene mutations
      had a higher symptom severity score and higher incidence of appendectomy. The
      broad spectrum of mutations may reflect intercultural interactions of ethnic
      groups in Anatolia. Nation-wide studies may help to determine the relationships
      among demographic, clinical and genetic features of FMF.

PMID- 19845844
TI  - Depressive tendency in children with growth hormone deficiency.
AB  - AIM: This study assessed changes in depressive tendency of children with growth
      hormone deficiency. METHODS: The 41 children with growth hormone deficiency were
      assessed using the Depression Self-Rating Scale for Children. A score of 16 or
      more indicated a depressive tendency. The first assessment was carried out before
      growth hormone treatment, and the second one was carried out at 6 months or
      longer after the beginning of growth hormone treatment. RESULTS: The Depression
      Self-Rating Scale for Children improved significantly from 9.7 +/- 6.1 points
      before treatment to 6.9 +/- 4.6 points after treatment (P= 0.0013). A depressive
      tendency was observed in six patients (15%) before growth hormone treatment, and
      in two patients (5%) after treatment. No significant relationship was observed
      between the decrease in the score and the length of the treatment. A significant
      improvement was observed for 6 of the 18 items in the Depression Self-Rating
      Scale for Children. CONCLUSION: A depressive tendency was relatively common in
      children with growth hormone deficiency, and the Depression Self-Rating Scale for
      Children was decreased after growth hormone treatment. These results suggest that
      growth hormone treatment may have positive effects on the psychosocial aspects in
      children with growth hormone deficiency.

PMID- 19845845
TI  - Rapid national survey of renal stones in New Zealand infants.
AB  - AIM: The aim of this study was to determine if there have been recent serious
      renal problems because of melamine among infants in New Zealand. METHODS: New
      Zealand paediatricians were surveyed in October 2008 using the New Zealand
      Paediatric Surveillance Unit network. RESULTS: Two cases of renal stones and none
      of unexplained renal failure in the previous 12 months were reported. Both cases
      of renal stones had an identifiable cause, and neither had features of melamine
      related stones. CONCLUSION: This survey confirmed the expectation that this was
      not a discernible problem of recent serious melamine-associated renal damage in
      New Zealand. The method did however prove to be an effective way of undertaking a
      rapid determination of a possible recent serious health problem among children.

PMID- 19845846
TI  - Sexual satisfaction in men with erectile dysfunction: correlates and potential
      predictors.
AB  - INTRODUCTION: Sexual satisfaction is an important treatment objective for men
      with erectile dysfunction (ED). AIMS: To evaluate potential associations between
      International Index of Erectile Function (IIEF) satisfaction at study endpoint
      and a range of baseline, on-treatment, and endpoint variables. METHODS: An
      exploratory analysis was conducted involving 3,935 subjects with ED randomized to
      on-demand tadalafil (N = 2,824) or placebo (N = 1,111) in randomized, controlled
      trials across 28 countries. Patients achieving scores > or =16 on IIEF questions
      7, 8, 13, and 14 at study endpoint were operationally defined as satisfied (vs.
      <16, not satisfied). Multivariate logistic regression and other analyses were
      conducted to ascertain correlates and potential predictors of improvements in the
      IIEF-erectile function domain (IIEF-EF). MAIN OUTCOME MEASURES: Satisfaction on
      the IIEF at study endpoint, on-treatment improvements in IIEF-EF, and endpoint
      sexual frequency. RESULTS: Patients who were satisfied with sexual function were
      on average younger and had less severe ED, a shorter history of the condition,
      and no history of vascular disorders, hypertension, or diabetes mellitus/insulin
      use at baseline (P < 0.01 vs. not satisfied for each). Satisfied patients were
      also more likely to experience a > or =4-point increase on the IIEF-EF domain on
      treatment (adjusted odds ratio [OR] = 22.4; 95% CI = 17.6-28.5; P < 0.0001) or
      IIEF-EF > or =26 at endpoint (adjusted OR = 41.0; 95% CI = 33.6-50.2; P <
      0.0001). Satisfaction emerged as a strong correlate of a > or =4-point increase
      in the IIEF-EF on treatment; however, as a correlate of endpoint sexual
      frequency, baseline sexual frequency was stronger than endpoint satisfaction.
      CONCLUSIONS: Satisfaction is associated with certain baseline, on-treatment, and
      endpoint variables in ED patients. Further studies are needed to confirm these
      preliminary findings and explore their meaning for female partners.

PMID- 19845847
TI  - Slow oscillations in human non-rapid eye movement sleep electroencephalogram:
      effects of increased sleep pressure.
AB  - Slow oscillations (< 1 Hz) in the non-rapid eye movement (NREM) sleep
      electroencephalogram (EEG) result from slow membrane potential fluctuations of
      cortical neurones, alternating between a depolarized up-state and a
      hyperpolarized down-state. They are thought to underlie the restorative function
      of sleep. We investigated the behaviour of slow oscillations in humans under
      increased sleep pressure to assess their contribution to sleep homeostasis. EEG
      recordings (C3A2) of baseline and recovery sleep after sleep deprivation (eight
      healthy males, mean age 23 years; 40 h of prolonged wakefulness) were analysed.
      Half-waves were defined as positive or negative deflections between consecutive
      zero crossings in the 0.5-2 Hz range of the band-pass filtered EEG. Increased
      sleep pressure resulted in a redistribution of half-waves between 0.5 and 2 Hz:
      the number of half-waves per minute was reduced below 0.9 Hz while it was
      increased above 1.2 Hz. EEG power was increased above 1 Hz. The increase in
      frequency was accompanied by increased slope of the half-waves and decreased
      number of multi-peak waves. In both baseline and recovery sleep, amplitude and
      slope were correlated highly over a broad frequency range and positive half-waves
      were characterized by a lower frequency than the negative ones, pointing to a
      longer duration of up- than down-states. We hypothesize that the higher frequency
      of slow oscillatory activity after prolonged wakefulness may relate to faster
      alternations between up- and down-states at the cellular level under increased
      sleep pressure. This study does not question slow-wave activity as a marker of
      sleep homeostasis, as the observed changes occurred within the same frequency
      range.

PMID- 19845848
TI  - Involvement of sympathetic function in the sleep-related change of gastric
      myoelectrical activity in rats.
AB  - The gastric myoelectrical activity (GMA) fluctuates across sleep-wake states as a
      result of modulation by the brain-gut axis. The role of the autonomic nervous
      system in this phenomenon, however, was not elucidated fully. Through
      simultaneous recording and subsequent continuous power spectral analysis of
      electroencephalogram, electromyogram, electrocardiogram and electrogastromyogram
      (EGMG) in 16 freely moving Wistar rats, the sleep-wake states of the animals were
      defined and indices of cardiac autonomic regulation and GMA were calculated. We
      found that both cardiac autonomic regulation and GMA fluctuated through sleep
      wake cycles. Correlation analysis further revealed significant correlations
      between EGMG power and each of the R-R interval, high-frequency power, low
      frequency power, very-low-frequency power, low-frequency power to high-frequency
      power ratio and normalized low-frequency power of heart rate variability with
      respect to their trend of change across different sleep-wake states. These
      results suggest that the sleep-wake-related change of GMA was related to
      sympathovagal balance. The sympathetic nerve may play a more important role in
      the central modulation of GMA than perceived previously.

PMID- 19845849
TI  - The effects of sleep deprivation in humans: topographical electroencephalogram
      changes in non-rapid eye movement (NREM) sleep versus REM sleep.
AB  - Studies on homeostatic aspects of sleep regulation have been focussed upon non
      rapid eye movement (NREM) sleep, and direct comparisons with regional changes in
      rapid eye movement (REM) sleep are sparse. To this end, evaluation of
      electroencephalogram (EEG) changes in recovery sleep after extended waking is the
      classical approach for increasing homeostatic need. Here, we studied a large
      sample of 40 healthy subjects, considering a full-scalp EEG topography during
      baseline (BSL) and recovery sleep following 40 h of wakefulness (REC). In NREM
      sleep, the statistical maps of REC versus BSL differences revealed significant
      fronto-central increases of power from 0.5 to 11 Hz and decreases from 13 to 15
      Hz. In REM sleep, REC versus BSL differences pointed to significant fronto
      central increases in the 0.5-7 Hz and decreases in the 8-11 Hz bands. Moreover,
      the 12-15 Hz band showed a fronto-parietal increase and that at 22-24 Hz
      exhibited a fronto-central decrease. Hence, the 1-7 Hz range showed significant
      increases in both NREM sleep and REM sleep, with similar topography. The parallel
      change of NREM sleep and REM sleep EEG power is related, as confirmed by a
      correlational analysis, indicating that the increase in frequency of 2-7 Hz
      possibly subtends a state-aspecific homeostatic response. On the contrary, sleep
      deprivation has opposite effects on alpha and sigma activity in both states. In
      particular, this analysis points to the presence of state-specific homeostatic
      mechanisms for NREM sleep, limited to <2 Hz frequencies. In conclusion, REM sleep
      and NREM sleep seem to share some homeostatic mechanisms in response to sleep
      deprivation, as indicated mainly by the similar direction and topography of
      changes in low-frequency activity.

PMID- 19845850
TI  - The effects of hepatitis C recurrence on health-related quality of life in liver
      transplant recipients.
AB  - Orthotopic liver transplantation (OLT) remains the definitive treatment for
      hepatitis C (HCV). Although HCV is the number one indication for OLT in the USA,
      health-related quality of life (HRQOL) scores are consistently lower for HCV
      patients when compared with all OLT indications. HCV is unique in that 95% of
      transplanted patients experience virological recurrence of HCV hepatitis. Despite
      few physical manifestations of disease at the time of HCV recurrence, patients
      report an impaired quality of life and functional status compared with OLT
      recipients without recurrence. Studies show that patient knowledge of the
      diagnosis of recurrent HCV alone can negatively impact HRQOL. This suggests that
      patients perceive themselves as unwell and have significant changes in their
      mental and physical health despite the absence of disease-related complications.
      Multiple studies show that patients with HCV recurrence report significantly
      higher scores for depression, anxiety and psychological distress. However, only a
      limited number of studies have investigated the influence of gender, HCV
      genotype, or HCV antiviral treatment on the HRQOL of OLT recipients with HCV
      recurrence. This review article describes what is currently known about the
      impact of recurrent HCV on HRQOL specifically after OLT. Understanding modifiable
      factors on HRQOL after HCV recurrence in OLT patients can greatly aid in
      tailoring multidimensional interventions to improve patient HRQOL.

PMID- 19845851
TI  - Rapamycin and CCI-779 inhibit the mammalian target of rapamycin signalling in
      hepatocellular carcinoma.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR), which phosphorylates p70S6K
      and 4EBP1 and activates the protein translation process, is upregulated in
      cancers and its activation may be involved in cancer development. AIMS: In this
      study, we investigated the tumour-suppressive effects of rapamycin and its new
      analogue CCI-779 on hepatocellular carcinoma (HCC). METHODS: Rapamycin and its
      new analogue CCI-779 were applied to treat HCC cells. Cell proliferation, cell
      cycle profile and tumorigenicity were analysed. RESULTS: In human HCCs, we
      observed frequent (67%, 37/55) overexpression of mTOR transcripts using real-time
      reverse transcriptase-polymerase chain reaction. Upon drug treatment, PLC/PRF/5
      showed the greatest reduction in cell proliferation using the colony formation
      assay, as compared with HepG2, Hep3B and HLE. Rapamycin was a more potent
      antiproliferative agent than CCI-779 in HCC cell lines. Proliferation assays by
      cell counting showed that the IC(50) value of rapamycin was lower than that of
      CCI-779 in PLC/PRF/5 cells. Furthermore, flow cytometric analysis showed that
      both drugs could arrest HCC cells in the G(1) phase but did not induce apoptosis
      of these cells, suggesting that these mTOR inhibitors are cytostatic rather than
      cytotoxic. Upon rapamycin and CCI-779 treatment, the phosphorylation level of
      mTOR and p70S6K in HCC cell lines was significantly reduced, indicating that both
      drugs can suppress mTOR activity in HCC cells. In addition, both drugs
      significantly inhibited the growth of xenografts of PLC/PRF/5 cells in nude mice.
      CONCLUSIONS: Our findings indicate that rapamycin and its clinical analogue CCI
      779 possess tumour-suppressive functions towards HCC cells.

PMID- 19845852
TI  - Hepatic resection for inflammatory hepatocellular adenomas: pathological
      identification of micronodules expressing inflammatory proteins.
AB  - BACKGROUND: Inflammatory hepatocellular adenoma (IHCA) defines a subgroup of
      hepatocellular adenomas characterized by the expression of members of the acute
      phase inflammatory response [(serum amyloid A protein (SAA) and C-reactive
      protein (CRP)]. IHCA are unique or multiple as defined by the presence of several
      nodule(s) larger than 10 mm using both imaging and macroscopic observation.
      Frequently, additional micronodules (<10 mm), previously undetected by imaging,
      can be observed in resected specimens. AIMS: To analyse micronodules in multiple
      (group 1, nine patients) and single (group 2, eight patients) IHCA cases,
      immunohistochemistry using SAA and CRP antibodies was performed on all nodules
      detected under macroscopic examination as well as on surrounding tissue with no
      visible nodules. RESULTS: Nodules of different sizes (>5 < or = 10 mm, > or = 1 <
      or = 5 mm) were found in group 1, whereas only rare nodules in the mm range were
      found in group 2. Micronodules shared the characteristics of large nodules, which
      justified surgery such as inflammatory infiltrates, abnormal arteries, sinusoidal
      dilatation or peliosis. However, the number of these characteristics was
      proportional to the size of the nodules. CONCLUSION: This study demonstrates that
      the real number of IHCA is greater than that predicted from imaging-based
      analyses. In addition, we show that patients with more than one nodule present a
      greater chance to display more and larger undetected micronodules than patients
      with a single nodule.

PMID- 19845853
TI  - A large liver tumour.

PMID- 19845854
TI  - ABCB11 gene mutations in Chinese children with progressive intrahepatic
      cholestasis and low gamma glutamyltransferase.
AB  - BACKGROUND: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a
      severe autosomal recessive liver disorder of childhood that can cause cholestasis
      and progress to end-stage liver disease. ABCB11 gene mutations causing PFIC2 have
      been reported in some population groups, but not in mainland Chinese. AIMS: To
      elucidate the existence of and characterize ABCB11 gene mutations in mainland
      Chinese with progressive intrahepatic cholestasis and low gamma
      glutamyltransferase (GGT). METHODS: Twenty-four children presenting with
      progressive intrahepatic cholestasis and low GGT were admitted to a tertiary
      paediatric hospital in eastern China from January 2004 to July 2007. All encoding
      exons and flanking areas of the ABCB11 gene were sequenced. Hepatic
      histopathology results were obtained by review of the medical record. RESULTS:
      Twelve novel mutations of ABCB11 gene were found in seven patients: three
      nonsense mutations, six missense mutations, two splicing mutations and one
      intronic mutation. Giant cell transformation of hepatocytes was demonstrated in
      all the four patients with ABCB11 mutations and four of 12 patients without
      mutations in coding sequences of ABCB11 gene who received liver needle biopsy.
      CONCLUSIONS: ABCB11 gene mutations play an important role in Chinese patients
      with progressive intrahepatic cholestasis and low GGT. The characteristics of
      ABCB11 gene mutations in Chinese are different from other population groups.
      Histological examination may be helpful in diagnosis of PFIC2.

PMID- 19845855
TI  - Clinical significance and expression of cyclin kinase subunits 1 and 2 in
      hepatocellular carcinoma.
AB  - BACKGROUND: The mammalian cyclin kinase subunit (Cks) family has two members,
      Cks1 and Cks2, which were identified based on the protein sequence homology to
      yeast Cks. Overexpression of Cks1 and Cks2 has been reported to be associated
      with high aggressiveness and a poor prognosis in various malignancies, including
      gastric, breast and prostate carcinomas. Yet, whether Cks1 and Cks2 are
      overexpressed in hepatocellular carcinoma (HCC) remains uncharacterized. AIMS: To
      investigate whether overexpression of the Cks family is clinically relevant to
      HCC, and whether expression patterns of Cks1 and Cks2 in HCC have diagnostic and
      prognostic value. METHODS: Real-time quantitative reverse transcriptase
      polymerase chain reaction, immunostaining and Western blot analyses were used to
      detect the expression of Cks1 and Cks2 at the mRNA and protein levels
      respectively. The associations between Cks1 and Cks2 expressions and clinical
      features, as well as the association between Cks1 or Cks2 and p27(kip1)
      expressions in HCC, were analysed. RESULTS: Expressions of Cks1 and Cks2 at both
      mRNA and protein levels were significantly higher in HCC than those in the
      adjacent noncancerous tissues (including chronic hepatitis and cirrhosis) and
      normal liver tissues. Overexpressions of Cks1 and Cks2 in HCC were closely
      associated with poor differentiation features. The expressions of both Cks1 and
      Cks2 were negatively associated with p27(kip1) at the protein level. CONCLUSIONS:
      Overexpression of Cks1 and Cks2 is associated with the aggressive tumour
      behaviours of HCC, and thus has diagnostic and prognostic value. Further efforts
      are needed to develop novel biomarkers for HCC based on CKs1 and Cks2
      expressions.

PMID- 19845856
TI  - Major histocompatibility complex variation at class II DQA locus in the brown
      hare (Lepus europaeus).
AB  - The major histocompatability complex (MHC) is a multigene family of receptors
      that bind and present antigenic peptides to T-cells. Genes of the MHC are
      characterized by an outstanding genetic polymorphism, which is considered to be
      maintained by positive selection. Sites involved in peptide binding form binding
      pockets (P) that are collectively termed the peptide-binding region (PBR). In
      this study, we examined the level of MHC genetic diversity within and among
      natural populations of brown hare (Lepus europaeus) from Europe and Anatolia
      choosing for analysis of the second exon of the DQA locus, one of the most
      polymorphic class II loci. We aimed at an integrated population genetic analysis
      of L. europeaus by (i) correlating MHC polymorphism to genetic variability and
      phylogenetic status estimated previously from maternally (mtDNA) and biparentally
      (allozymes, microsatellites) inherited loci; and (ii) comparing full-length exon
      amino acid polymorphism with functional polymorphism in the PBR and the binding
      pockets P1, P6 and P9. A substantial level of DQA exon 2 polymorphism was
      detected with two completely different set of alleles between the Anatolian and
      European populations. However, the phylogeny of full-length exon 2 Leeu-DQA
      alleles did not show a strong phylogeographic signal. The presence of balancing
      selection was supported by a statistically significant excess of nonsynonymous
      substitutions over synonymous in the PBR and a trans-species pattern of evolution
      detected after phylogenetic reconstruction. The differentiating patterns detected
      between genetic and functional polymorphism, i.e. the number and the distribution
      of pocket variants within and among populations, indicated a hierarchical action
      of selection pressures.

PMID- 19845857
TI  - Contrasting mtDNA diversity and population structure in a direct-developing
      marine gastropod and its trematode parasites.
AB  - The comparative genetic structure of hosts and their parasites has important
      implications for their coevolution, but has been investigated in relatively few
      systems. In this study, we analysed the genetic structure and diversity of the
      New Zealand intertidal snail Zeacumantus subcarinatus (n = 330) and two of its
      trematode parasites, Maritrema novaezealandensis (n = 269) and Philophthalmus sp.
      (n = 246), using cytochrome c oxidase subunit I gene (COI) sequences. Snails and
      trematodes were examined from 11 collection sites representing three regions on
      the South Island of New Zealand. Zeacumantus subcarinatus displayed low genetic
      diversity per geographic locality, strong genetic structure following an
      isolation by distance pattern, and low migration rates at the scale of the study.
      In contrast, M. novaezealandensis possessed high genetic diversity, genetic
      homogeneity among collection sites and high migration rates. Genetic diversity
      and migration rates were typically lower for Philophthalmus sp. compared to M.
      novaezealandensis and it displayed weak to moderate genetic structure. The
      observed patterns likely result from the limited dispersal ability of the direct
      developing snail and the utilization of bird definitive hosts by the trematodes.
      In addition, snails may occasionally experience long-distance dispersal.
      Discrepancies between trematode species may result from differences in their
      effective population sizes and/or life history traits.

PMID- 19845858
TI  - Genetic relatedness in groups of the humbug damselfish Dascyllus aruanus: small,
      similar-sized individuals may be close kin.
AB  - Kin selection plays an important role in the evolution of social behaviour in
      terrestrial systems. The extent to which kin selection influences the evolution
      of social behaviour in marine systems is largely unexplored. Generally, it is
      considered that kin selection is irrelevant in marine systems, because it is
      assumed that the dispersing larval phase of marine organisms will break up kin
      associations. Here, we challenge this assumption and investigate the opportunity
      for kin selection in a coral reef fish: the humbug damselfish Dascyllus aruanus.
      This fish lives in groups composed of a large male and a number of smaller
      females and nonbreeders. We use 10 polymorphic microsatellite loci to assess the
      relatedness of 265 individuals from 35 groups. The mean coefficient of
      relatedness among group members is 0.01 +/- 0.04, suggesting that individuals are
      not associated with close relatives. However, the distribution of pairwise
      relatedness of individuals within groups has an overabundance of positive values,
      and indicates that there might be 35 pairs of close relatives within groups.
      Further analyses reveal that close relatives likely are similar in size and small
      in size, suggesting that they might have recruited together. We conclude that it
      is possible for kin selection to operate in D. aruanus, but kin recognition will
      be a prerequisite for such selection. This study reveals that individuals can be
      associated with close relatives, and there is a hidden potential for kin
      selection, during certain parts of the life cycle of coral reef fishes.

PMID- 19845859
TI  - Do complex population histories drive higher estimates of substitution rate in
      phylogenetic reconstructions?
AB  - Our curiosity about biodiversity compels us to reconstruct the evolutionary past
      of species. Molecular evolutionary theory now allows parameterization of
      mathematically sophisticated and detailed models of DNA evolution, which have
      resulted in a wealth of phylogenetic histories. But reconstructing how species
      and population histories have played out is critically dependent on the
      assumptions we make, such as the clock-like accumulation of genetic differences
      over time and the rate of accumulation of such differences. An important
      stumbling block in the reconstruction of evolutionary history has been the
      discordance in estimates of substitution rate between phylogenetic and pedigree
      based studies. Ancient genetic data recovered directly from the past are
      intermediate in time scale between phylogenetics-based and pedigree-based
      calibrations of substitution rate. Recent analyses of such ancient genetic data
      suggest that substitution rates are closer to the higher, pedigree-based
      estimates. In this issue, Navascues & Emerson (2009) model genetic data from
      contemporary and ancient populations that deviate from a simple demographic
      history (including changes in population size and structure) using serial
      coalescent simulations. Furthermore, they show that when these data are used for
      calibration, we are likely to arrive at upwardly biased estimates of mutation
      rate.

PMID- 19845860
TI  - Evolution rampant: house mice on Madeira.
AB  - House mice are extra-ordinary animals -extra-ordinary in the literal sense of
      that word. They are pests - but also a valued laboratory animal. They are
      generalized rodents - and successful in habitats from tundra to tropics and from
      sea-level to high altitudes. They have differentiated into a perplexity of taxa,
      yet differ little in their general morphology. They were long scorned by
      ecologists as recently arrived commensals, but are increasingly illuminating
      evolutionary processes as new techniques are applied to their study. Local forms,
      once valued only by taxonomists, are proving ever more interesting as their
      genetics are probed. In 1992, Mathias & Mira described the apparently unexciting
      characteristics of mice living on the two main islands of the Madeira group, 600
      km west of continental Portugal. Then in 2000, Britton-Davidian et al. discovered
      that there were at least six chromosomal (Robertsonian) races on the main island.
      In the past decade, studies of molecular and mitochondrial genomes have shown an
      array of variables and posed questions about the origins and subsequent evolution
      of these island mice. In this issue of Molecular Ecology, Forster et al. report
      on the mtDNA haplotypes found on the island and in mainland Portugal, discuss the
      probable source of the island colonizers, and consider data which might give
      information about the timing of the colonizing event(s).

PMID- 19845861
TI  - Up against the edge: invasive species as testbeds for basic questions about
      evolution in heterogeneous environments.
AB  - Yogi Berra is often credited with having opined that 'prediction is very
      difficult, especially about the future'. There is no discipline for which this
      statement holds with more force than invasion biology, where it has been
      historically very challenging to predict the fate of introduced species
      (Williamson 2006). Some species after introduction quickly go extinct. Other
      relatively similar species may persist, but with little spread from their initial
      beachheads. Yet others can become aggressive invaders, with devastating
      consequences for native communities and ecosystems. This lack of predictability
      may of course sometimes reflect a simple lack of knowledge, both about key
      features of a species' basic biology, and about the environmental and community
      milieu in which invasion occurs (Williamson 2006). However, unpredictability may
      also arise from a fundamental fact about populations of living organisms - they
      almost always contain genetic variation, and so are not fixed entities responding
      to an environmental template, but instead labile in how they cope with the
      environment, over many spatial and temporal scales. Chance vicissitudes in the
      origination, maintenance and spatial organization of genetic variation could play
      a large role in generating the observed unpredictability in the fates of
      introduced species. The degree to which a particular introduced species becomes
      'invasive'- to the extent of coming to the attention of worried land managers,
      governmental officials and the public - may reflect in part its capacity for
      adaptive evolution across a wide range of environmental conditions.

PMID- 19845862
TI  - Cerebral mycosis: 7-year retrospective series in a tertiary center.
AB  - This study focuses on the epidemiology, clinical manifestations, risk factors,
      diagnosis and outcome of all cases of central nervous system (CNS) fungal
      infections in a tertiary center. Medical records of 18 patients of culture-proven
      CNS fungal infections were retrospectively reviewed from 2000 to 2007, including
      12 isolated from the cerebrospinal fluid (CSF) and seven from tissue biopsy.
      Patient demographic data included 10 males and eight females. The mean age was 55
      years (range: 24-89 years). All but one patient were immunocompromised. Fungal
      organisms isolated from CSF included: Cryptococcous neoformans (8 patients),
      Coccidioides immitis (3 patients), and Aspergillus versicolor (1 patient).
      Histopathology of seven biopsy cases revealed groups of pigmented golden-brown
      fungal forms in three cases; three cases showed septate fungi, two of which had
      melanin in their walls; and one case showed multiple round spherules. These cases
      on microbiological cultures grew Coccidioides immitis (1 patient), Aspergillus
      fumigatus (1 patient), Cladophialophora bantiana (2 patients), Fonsecaea
      monophora (1 patient) and Scedosporium apiospermum (2 patients). Five of the
      seven fungal organisms isolated from tissue biopsies were dematiaceous fungi.
      Twelve patients died after a period of a few weeks to months, two were lost to
      follow-up, and four are alive with severe neurological sequelae. CNS fungal
      infections in our cohort were more common in patients post-transplant and with
      hematologic malignancies. In our series, rare dematiaceous fungi are emerging
      agents for cerebral mycosis. The outcome of CNS fungal infections is poor despite
      vigorous antifungal therapy.

PMID- 19845863
TI  - Cytogenetic study of glioneuronal tumor with neuropil-like islands: a case
      report.
AB  - Glioneuronal tumor with neuropil-like islands (GTNI) is a recently recognized
      glioneuronal neoplasm but it was classified as an astrocytic tumor by the World
      Health Organization (WHO) in 2007. We performed a cytogenetic study in a case of
      GTNI arising in a 55-year-old man and analyzed its genetic alteration. It
      presented as a heterogeneously enhancing, multi-lobulating solid mass on MRI.
      Histopathologically, the tumor showed the biphasic feature of the predominating
      micronodular neuropil-like islands and the diffusely infiltrating glial
      component. In addition, the prominent blood vessels with perivascular
      hyalinization were observed. On cytogenetic study, loss of 4q, 5q, 11p and gain
      of 6p, 7, 8, 11q, 12p, 15q were found. The remaining tumor after subtotal
      resection progressed 7 months later, despite combined chemo- and radiotherapy.
      From the results, it seems that GTNI does not share pathologic or genetic
      features with conventional astrocytoma, suggesting a unique entity with
      aggressive behavior.

PMID- 19845864
TI  - Intraparenchymal myofibromatosis of the brain in an adult: report of an unusual
      case.
AB  - An unusual case of intraparenchymal myofibromatosis of the brain occurring in a
      29-year-old woman is described. Preoperative CT and MRI examinations revealed two
      well-circumscribed nodular masses localized in the wall of the left lateral
      ventricle and right temporal lobe, respectively. Both masses were completely
      resected, and the patient remains disease-free 2 years post-surgery.
      Histopathologically, the lesions were characterized by stratification. From outer
      to inner, there was a reactive glial component, lamellated well-differentiated
      muscle-like cells, densely compact collagen fibers and cellular tumor with
      nodular and hemangiopericytoma-like patterns, respectively. The myofibroblastic
      nature of this tumor was verified by immunohistochemical staining and
      ultrastructural analysis. Intraparenchymal myofibromatosis may be confused with,
      and should be distinguished from, meningioma, myopericytoma, solitary fibrous
      tumor, leiomyoma and inflammatory myofibroblastic tumor for accurate diagnosis
      and optimal treatment.

PMID- 19845865
TI  - Malignant solitary fibrous tumor arising from the pineal region: case study and
      literature review.
AB  - We report a case of malignant solitary fibrous tumor involving the pineal region
      in a 49-year-old woman. The patient presented with headache, slowly progressive
      weakness of the right lower extremities and upgaze palsy over the past year.
      Histologically, the tumor was composed of moderately hypercellular proliferated
      spindle cells with eosinophilic collagen bands. These cells were diffusely and
      strongly immunoreactive with CD34, CD99, and vimentin, but were negative with
      epithelial membrane antigen, S-100 protein, Bcl-2, smooth muscle actin,
      cytokeratin and glial fibrillary antigenic protein. MIB-1 labeling indices and
      mitosis rates were 7.3 +/- 1.8% and 5 per 10 high power fields, respectively.
      Ultrastructural examination revealed that the neoplastic cells had features of
      fibroblastic differentiation. Differential diagnoses included fibrous meningioma
      and hemangiopericytoma. The present case provides one unique example of a rare
      entity to the already diverse spectrum of the pineal region neoplasms encountered
      in neuropathology.

PMID- 19845866
TI  - Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and
      induces axonal regrowth of injured spinal cord.
AB  - It has been demonstrated that transplantation of bone marrow mesenchymal stem
      cells (BMSCs) improves recovery of injured spinal cord in animal models. However,
      the mechanism of how BMSCs promote repair of injured spinal cord remains under
      investigation. The present study investigated the neural differentiation of
      BMSCs, the lesion volume and axonal regrowth of injured spinal cord after
      transplantation. Seven days after spinal cord injury, 3 x 10(5) BMSCs or PBS
      (control) was delivered into the injury epicenter of the spinal cord. At 8 weeks
      after spinal cord injury, transplantation of BMSCs reduced the volume of cavity
      and increased spared white matter as compared to the control. BMSCs did not
      express the cell marker of neurons, astrocytes and oligodendrocytes in injured
      spinal cord. Transmission electron microscopic examination displayed an increase
      in the number of axons in BMSC rats. The effect of BMSCs on growth of neuronal
      process was further investigated by using a coculture system. The length and the
      number of neurites from spinal neurons significantly increased when they
      cocultured with BMSCs. PCR and immunochemical analysis showed that BMSCs
      expressed brain-derived neurotrophic factor (BDNF) and glia cell line-derived
      neurotrophic factor (GDNF). These findings demonstrate that transplantation of
      BMSCs reduces lesion volume and promotes axonal regrowth of injured spinal cord.

PMID- 19845867
TI  - Contribution of animal models to the understanding of the metabolic syndrome: a
      systematic overview.
AB  - The metabolic syndrome (MetS) is one of the most important challenges to public
      health and biomedical research. Animal models of MetS, such as leptin-deficient
      obese mice, obese spontaneously hypertensive rats, JCR: LA-cp rats and the
      Ossabaw and Gottingen minipigs, have contributed to our understanding of the
      pathophysiological basis and the development of novel therapies. For a complex
      disease syndrome, no animal model can be expected to serve all needs of research.
      Although each animal model has limitations and strengths, used together in a
      complementary fashion, they are essential for research on the MetS and for rapid
      progress in understanding the aetiology and pathogenesis towards a cure. The
      purpose of this review is to assess how current animal models contributed to our
      knowledge of the human MetS, and to systematically evaluate the strengths and
      weaknesses of the currently available 78 animal models from 11 species.

PMID- 19845868
TI  - Obesity and low-grade inflammation: a paediatric perspective.
AB  - Childhood obesity is a major public health problem. Low-grade inflammation, a
      hallmark characterizing adult obesity, may be a pivotal mechanism linking obesity
      to its numerous systemic complications, with adipose tissue depots secreting and
      producing inflammatory mediators and visceral fat displaying an increased
      inflammatory profile. While knowledge is relatively scarce regarding the
      importance of the adipose tissue inflammation process in children, identifying
      its contribution in childhood obesity and the associated influences of age, sex,
      weight status, growth, and adipose depot phenotypes are crucial for understanding
      physiopathology and implementing early intervention strategies. We review the
      latest research linking obesity and inflammation in childhood focusing on serum
      inflammatory markers and the effectiveness of lifestyle interventions in
      improving systemic inflammation. Generally, there are significant correlations
      between body mass index and increased c-reactive protein and decreased
      adiponectin levels in children; these levels tend to be improved in interventions
      resulting in approximately 5% weight loss, regardless of the type or length of
      intervention. There is a need for further research measuring other inflammatory
      mediators (e.g. tumour necrosis factor (TNF)-alpha, IL-6, IL-8) and histological
      studies examining immune cell infiltration in adipose tissue depots in obese
      children.

PMID- 19845869
TI  - Variegate porphyria in a 46-year-old patient taking sibutramine for weight loss.
AB  - The acute hepatic porphyrias can cause life-threatening attacks of neurovisceral
      symptoms that mimic other acute medical conditions. Variegate porphyria caused by
      mutations in the protoporphyrinogen oxidase (PPOX) gene is a latent disorder
      characterized by exacerbations induced by fasting, alcohol consumption or certain
      drugs. We describe the case of a 46-year-old female patient presenting with a
      first episode of symptomatic porphyria after 10 d of sibutramine treatment for
      weight loss. Genetic analysis showed a heterozygous R168H hot spot mutation in
      the PPOX gene. A putative effect of sibutramine on the hepatic haem biosynthetic
      pathway and reduced food intake have likely caused this exacerbation of a
      porphyria attack. Although this may be the first case report of this kind, the
      risk of acute porphyria should be considered in patients using pharmacotherapy
      for obesity.

PMID- 19845871
TI  - Non-alcoholic fatty liver disease from pathogenesis to management: an update.
AB  - Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease
      in the Western world, is tightly associated with obesity and metabolic syndrome.
      NAFLD entails an increased cardiometabolic and liver-related risk, the latter
      regarding almost exclusively non-alcoholic steatohepatitis (NASH), the
      progressive form of NAFLD. Pathogenetic models encompass altered hepatic lipid
      partitioning and adipokine action, increased oxidative stress, free fatty acid
      lipotoxicity. On this basis, lifestyle-, drug- or surgically induced weight loss,
      insulin sensitizers, antioxidants, lipid-lowering drugs have been evaluated in
      NAFLD/NASH. Most trials are small, of short duration, nonrandomized, without
      histological end points, thus limiting assessment of long-term safety and
      efficacy of proposed treatments. All NAFLD patients should be evaluated for their
      metabolic, cardiovascular and liver-related risk. Liver biopsy remains the gold
      standard for staging NAFLD, but non-invasive methods are under intense
      development. Weight loss through lifestyle intervention is the initial approach,
      because of established efficacy on NAFLD-associated cardiometabolic
      abnormalities, and to emerging benefits on necroinflammation and overall disease
      activity in NASH. Bariatric surgery warrants further evaluation before it can be
      routinely considered in morbidly obese NASH. Larger- and longer-duration
      randomized trials assessing safety and benefits of drugs on patient-oriented
      outcomes are needed before pharmacological treatment can be routinely recommended
      for NASH.

PMID- 19845870
TI  - Regulation of lipid metabolism by energy availability: a role for the central
      nervous system.
AB  - The central nervous system (CNS) is crucial in the regulation of energy
      homeostasis. Many neuroanatomical studies have shown that the white adipose
      tissue (WAT) is innervated by the sympathetic nervous system, which plays a
      critical role in adipocyte lipid metabolism. Therefore, there are currently
      numerous reports indicating that signals from the CNS control the amount of fat
      by modulating the storage or oxidation of fatty acids. Importantly, some CNS
      pathways regulate adipocyte metabolism independently of food intake, suggesting
      that some signals possess alternative mechanisms to regulate energy homeostasis.
      In this review, we mainly focus on how neuronal circuits within the hypothalamus,
      such as leptin- ghrelin-and resistin-responsive neurons, as well as
      melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on
      lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting
      the complicated interactions between peripheral signals and neuronal circuits
      regulating lipid metabolism might open new avenues for the development of new
      therapies preventing and treating obesity and its associated cardiometabolic
      sequelae.

PMID- 19845874
TI  - SKI knockdown inhibits human melanoma tumor growth in vivo.
AB  - The SKI protein represses the TGF-beta tumor suppressor pathway by associating
      with the Smad transcription factors. SKI is upregulated in human malignant
      melanoma tumors in a disease-progression manner and its overexpression promotes
      proliferation and migration of melanoma cells in vitro. The mechanisms by which
      SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here
      we show that human melanoma cells in which endogenous SKI expression was knocked
      down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed
      low mitotic rate and prominent apoptosis. These minute tumors exhibited critical
      signatures of active TGF-beta signaling including high levels of nuclear Smad3
      and p21(Waf-1), which are not found in the parental melanomas. To understand how
      SKI promotes tumor growth we used gain- and loss-of-function approaches and found
      that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI
      promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring
      phosphorylations of the Smad3 linker region in melanoma cells but not in normal
      human melanocytes. In this context, SKI is required for preventing TGF-beta
      mediated downregulation of the oncogenic protein c-MYC, and for inducing the
      plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis.
      Together, the results indicate that SKI exploits multiple regulatory levels of
      the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and
      apoptotic activities in spite of the likely presence of oncogenic mutations in
      melanoma tumors.

PMID- 19845878
TI  - The pentatricopeptide repeat protein OTP82 is required for RNA editing of plastid
      ndhB and ndhG transcripts.
AB  - Several hundred nucleus-encoded factors are required for regulating gene
      expression in plant organelles. Among them, the most numerous are the members of
      the pentatricopeptide repeat (PPR) protein family. We found that PPR protein
      OTP82 is essential for RNA editing of the ndhB-9 and ndhG-1 sites within
      transcripts encoding subunits of chloroplast NAD(P)H dehydrogenase. Despite the
      defects in RNA editing, otp82 did not show any phenotypes in NDH activity,
      stability or interaction with photosystem I, suggesting that the RNA editing
      events mediated by OTP82 are functionally silent even though they induce amino
      acid alterations. In agreement with this result, both sites are partially edited
      even in the wild type, implying the possibility that a single gene produces
      heterogeneous proteins that are functionally equivalent. Although only five
      nucleotides separate the ndhB-8 and ndhB-9 sites, the ndhB-8 site is normally
      edited in otp82 mutants, suggesting that both sites are recognized by different
      PPR proteins. OTP82 falls into the DYW subclass containing conserved C-terminal E
      and DYW motifs. As in CRR22 and CRR28, the DYW motif present in OTP82 is not
      essential for RNA editing in vivo.

PMID- 19845879
TI  - The 2-oxoglutarate/malate translocator mediates amino acid and storage protein
      biosynthesis in pea embryos.
AB  - Heterotrophic plastids of seeds perform many biosynthetic reactions.
      Understanding their function in crop plants is crucial for seed production.
      Physiological functions depend on the uptake of precursors by a range of
      different metabolite translocators. The 2-oxoglutarate/malate translocator gene
      (PsOMT), which is highly expressed during pea (Pisum sativum) embryo maturation,
      has an important role during seed storage. PsOMT functions have been studied by
      antisense repression in maturing pea embryos, and were found to reduce mRNA
      levels and transport rates of 2-oxoglutarate and malate by 50-70%. Combined
      metabolite and transcript profiling revealed that OMT repression affects the
      conversion of carbohydrates from sucrose into amino acids and proteins, decreases
      seed weight and delays maturation. OMT-repressed pea embryos have increased
      levels of organic acids, ammonia, and higher ratios of Asn : Asp and Gln : Glu.
      Decreased levels of most other amino acids indicate the reduced usage of organic
      acids and ammonia for amino acid biosynthesis in plastids, possibly caused by
      substrate limitation of the plastidial glutamine synthetase/glutamine-2
      oxoglutarate aminotransferase cycle. Expression of storage proteins is delayed,
      and mature seeds have reduced protein content. Downregulated gene expression of
      starch biosynthesis and plastidial glucose-6-phosphate transport in asOMT embryos
      reveals that decreased 2-oxoglutarate/malate transport capacity affects other
      pathways of central carbon metabolism. Gene expression analysis related to
      plastid physiology revealed that OMT repression delays differentiation of storage
      plastids, thereby maintaining gene expression associated with green chloroplasts.
      We conclude that OMT is important for protein-storing crop seeds, and is
      necessary for amino acid biosynthesis in pea seeds. In addition, carbon supply as
      mediated by OMT controls plastid differentiation during seed maturation.

PMID- 19845880
TI  - Sucrose non-fermenting kinase 1 (SnRK1) coordinates metabolic and hormonal
      signals during pea cotyledon growth and differentiation.
AB  - Seed development passes through developmental phases such as cell division,
      differentiation and maturation: each have specific metabolic demands. The
      ubiquitous sucrose non-fermenting-like kinase (SnRK1) coordinates and adjusts
      physiological and metabolic demands with growth. In protoplast assays sucrose
      deprivation and hormone supplementation, such as with auxin and abscisic acid
      (ABA), stimulate SnRK1-promoter activity. This indicates regulation by nutrients:
      hormonal crosstalk under conditions of nutrient demand and cell proliferation.
      SnRK1-repressed pea (Pisum sativum) embryos show lower cytokinin levels and
      deregulation of cotyledonary establishment and growth, together with
      downregulated gene expression related to cell proliferation, meristem maintenance
      and differentiation, leaf formation, and polarity. This suggests that at early
      stages of seed development SnRK1 regulates coordinated cotyledon emergence and
      growth via cytokinin-mediated auxin transport and/or distribution. Decreased ABA
      levels and reduced gene expression, involved in ABA-mediated seed maturation and
      response to sugars, indicate that SnRK1 is required for ABA synthesis and/or
      signal transduction at an early stage. Metabolic profiling of SnRK1-repressed
      embryos revealed lower levels of most organic and amino acids. In contrast,
      levels of sugars and glycolytic intermediates were higher or unchanged,
      indicating decreased carbon partitioning into subsequent pathways such as the
      tricarbonic acid cycle and amino acid biosynthesis. It is hypothesized that SnRK1
      mediates the responses to sugar signals required for early cotyledon
      establishment and patterning. As a result, later maturation and storage activity
      are strongly impaired. Changes observed in SnRK1-repressed pea seeds provide a
      framework for how SnRK1 communicates nutrient and hormonal signals from auxins,
      cytokinins and ABA to control metabolism and development.

PMID- 19845881
TI  - SlCCD7 controls strigolactone biosynthesis, shoot branching and mycorrhiza
      induced apocarotenoid formation in tomato.
AB  - The regulation of shoot branching is an essential determinant of plant
      architecture, integrating multiple external and internal signals. One of the
      signaling pathways regulating branching involves the MAX (more axillary branches)
      genes. Two of the genes within this pathway, MAX3/CCD7 and MAX4/CCD8, encode
      carotenoid cleavage enzymes involved in generating a branch-inhibiting hormone,
      recently identified as strigolactone. Here, we report the cloning of SlCCD7 from
      tomato. As in other species, SlCCD7 encodes an enzyme capable of cleaving cyclic
      and acyclic carotenoids. However, the SlCCD7 protein has 30 additional amino
      acids of unknown function at its C terminus. Tomato plants expressing a SlCCD7
      antisense construct display greatly increased branching. To reveal the underlying
      changes of this strong physiological phenotype, a metabolomic screen was
      conducted. With the exception of a reduction of stem amino acid content in the
      transgenic lines, no major changes were observed. In contrast, targeted analysis
      of the same plants revealed significantly decreased levels of strigolactone.
      There were no significant changes in root carotenoids, indicating that relatively
      little substrate is required to produce the bioactive strigolactones. The
      germination rate of Orobanche ramosa seeds was reduced by up to 90% on
      application of extract from the SlCCD7 antisense lines, compared with the wild
      type. Additionally, upon mycorrhizal colonization, C(13) cyclohexenone and C(14)
      mycorradicin apocarotenoid levels were greatly reduced in the roots of the
      antisense lines, implicating SlCCD7 in their biosynthesis. This work demonstrates
      the diverse roles of MAX3/CCD7 in strigolactone production, shoot branching,
      source-sink interactions and production of arbuscular mycorrhiza-induced
      apocarotenoids.

PMID- 19845882
TI  - Evaluation of prolactin receptor (PRLR) as candidate gene for male fertility in
      Hanoverian warmblood horses.
AB  - Stallion fertility has increasing importance as the artificial insemination is
      employed in horses more intensely. Molecular genetic markers may be useful tools
      to evaluate the stallion fertility before breeding. The prolactin receptor gene
      (PRLR) was chosen as a candidate for stallion fertility because of its influence
      on testicular and accessory sex gland function. Screening the equine PRLR gene
      for polymorphisms in Hanoverian stallions revealed two single nucleotide
      polymorphisms (SNPs). Association and haplotype analyses were performed in 162
      Hanoverian warmblood stallions for these intragenic SNPs using the least square
      means (LSM) of the pregnancy rate per oestrus for stallions and the paternal
      component and embryonic component of the breeding values (BV) of the pregnancy
      rate per oestrus. The two SNPs (BIEC2-589441, BIEC2-560860) showed significant
      associations using single marker and haplotype analysis with the embryonic and
      paternal component of BV and one SNP (BIEC2-560860) was also significantly
      associated with the LSM of the pregnancy rate per oestrus. This is the first
      report on an association of PRLR-associated genetic markers with fertility traits
      in stallions.

PMID- 19845883
TI  - Effect of early postpartum ovulation on fertility in dairy cows.
AB  - Our objectives were to determine the effects of early ovulation on fertility and
      uterine health of dairy cows. Four hundred and forty-five Holstein cows (185
      primiparous and 260 multiparous) from five herds were used. Blood samples were
      collected at 21, 35 and 49 days in milk (DIM) and cows were considered to be
      cyclic at 21 DIM (Cyc21) if serum progesterone (P4) concentration was above 1
      ng/ml, cyclic by 49 DIM (Cyc49) if P4 concentration was above 1 ng/ml at 35 or 49
      DIM, or not cyclic (NotCyc) if P4 concentration was below 1 ng/ml at all sample
      times. Endometrial cytology for diagnosis of subclinical endometritis was
      examined at 49 DIM in a subset of 414 cows. Cows in the group Cyc21 had increased
      hazard of insemination, for the first service, compared with cows in Cyc49
      [hazard ratio (HR) = 1.40; 95% CI = 1.10-1.79; p = 0.006] and NotCyc (HR = 2.07;
      95% CI = 1.52-2.82; p < 0.001). Cows in the Cyc49 group also had increased hazard
      of insemination compared with cows in the NotCyc group (HR = 1.47; 95% CI = 1.13
      1.93; p = 0.005). Median days to insemination were, respectively, 71, 76 and 96
      for cows in Cyc21, Cyc49 and NotCyc groups. Cows in Cyc21 had greater first
      service pregnancy per AI than Cyc49 [38.6 vs 28.1%; adjusted odds ratio (AOR) =
      1.67; 95% CI = 1.01-2.75; p = 0.04] and NotCyc (38.6 vs 23.6%; AOR = 2.08; 95% CI
      = 1.08-4.00; p = 0.03). Pregnancy per AI was similar in Cyc49 and NotCyc cows
      (28.1 vs 23.6%; AOR = 1.25; 95% CI = 0.70-2.24; p = 0.45). Cows in Cyc21 had
      increased hazard of pregnancy up to 300 DIM compared with Cyc49 (HR = 1.52; 95%
      CI = 1.17-1.96; p = 0.002) and NotCyc (HR = 1.98; 95% CI = 1.41-2.78; p < 0.001).
      Cows in Cyc49 tended to have increased hazard of pregnancy compared with NotCyc
      (HR = 1.31; 95% CI = 0.96-1.77; p = 0.09). Median days to pregnancy were,
      respectively, 103, 147 and 173 for cows in Cyc21, Cyc49 and NotCyc groups. Cows
      in the Cyc21 group had decreased prevalence of subclinical endometritis compared
      with cows in the NotCyc group (29.9 vs 43.7%; AOR = 0.53; 95% CI = 0.29-0.97; p =
      0.04); however, the prevalence did not differ from the Cyc49 group (29.9 vs
      39.1%; AOR = 0.68; 95% CI = 0.41-1.14; p = 0.15). Cyc49 cows had similar
      prevalence of subclinical endometritis compared with NotCyc cows (AOR = 0.77; 95%
      CI = 0.46-1.29; p = 0.32). Early postpartum ovulation was associated with
      improved uterine health and fertility.

PMID- 19845884
TI  - Culture of bovine embryos in polyester mesh sections: the effect of pore size and
      oxygen tension on in vitro development.
AB  - The purpose of this study was to assess the feasibility of polyester mesh culture
      for the in vitro production of bovine embryos, as polyester mesh is an
      alternative way for tracking individual embryos throughout culture using time
      lapse cinematography (TLC). Bovine embryos were isolated during in vitro culture
      using sections of three different polyethylene terephthalate (PET) mesh products.
      In vitro matured and fertilized bovine oocytes were cultured in the 217 * 217,
      230 * 230 or 238 * 238-MUm openings of PET mesh sections or in simple micro-drops
      (control) for 7 days under either 20% or 5% O(2) tensions. No difference in
      embryo developmental rates was found between the culture groups in terms of
      cleavage, blastocyst formation and blastocyst expansion irrespective of O(2)
      tension. In contrast, under 20% O(2) tension, blastocysts that developed in PET
      mesh with 217 * 217-MUm opening had significantly higher numbers of total and
      trophectoderm (TE) cells than control embryos; however, the numbers and
      proportions of inner cell mass (ICM) cells did not differ. Under 5% O(2) tension,
      no difference was found among the culture groups in the numbers of total, ICM and
      TE cells in embryos. All three PET mesh products investigated in this study were
      proven to be effective to prevent embryo movement. The results demonstrate that
      bovine embryos can be cultured in PET mesh sections without negative side-effects
      and suggest that embryo distance determined by the mesh affects embryo quality at
      atmospheric oxygen tension. Polyethylene terephthalate mesh with 217 * 217-MUm
      openings was found to be the most suitable for further application in TLC.

PMID- 19845885
TI  - Quality of care and service trajectories for people with intellectual
      disabilities: defining the aspects of quality from the client's perspective.
AB  - BACKGROUND: Care and service trajectories for people with intellectual
      disabilities (i.e. people with mental retardations) are routes within the
      healthcare delivery system that consist of all the steps that people with
      intellectual disabilities and their families have to take in order to realise the
      needed care and services. AIM: This article aims to identify the quality aspects
      of trajectories that are considered important by people with intellectual
      disabilities and their parents/relatives. In addition, it examines how these
      aspects are related to quality determinants mentioned in the literature on
      integrated care and to authoritative models for quality assessment of care and
      service delivery. METHODS: Quality aspects were collected during eight focus
      group discussions with people with intellectual disabilities or their
      parents/relatives. In addition, quality determinants of integrated care and
      authoritative models for quality assessment were selected by means of a thorough
      review of the literature. Finally, the quality aspects identified using focus
      groups were compared to the determinants and models found in the literature.
      RESULTS: The quality aspects presented by people with intellectual disabilities
      referred particularly to the immediate situation in receiving care and services,
      such as 'keeping appointments' and 'time and attention', whereas
      parents/relatives also referred to broader 'organisational issues', such as
      'access to support' and 'problems with placement'. The quality aspects, however,
      are minimally related to the quality determinants of integrated care, probably
      because clients and their parents/relatives find it difficult to have an overview
      of the coherence between the various actions that have to be performed, when
      going through the trajectories. In contrast, the quality aspects seem to fit into
      the domains of the authoritative models for quality assessment, probably because
      of the minimal focus of the models on long-term aspects in care and service
      delivery.

PMID- 19845886
TI  - The aspects school health nurses find important for successful health promotion.
AB  - BACKGROUND: The work of school health nurses has changed over time; today they
      focus on health promotion, i.e. encouraging and protecting pupils' health. AIM:
      The aim of this study was to explore school health nurses' conditions for health
      promotion work with pupils aged 13-15 years. METHODS: Eight school health nurses
      from eight different municipalities in Sweden were interviewed. Since the focus
      was on describing school health nurses' own experiences of their conditions for
      health promotion work, the research method used was based on Graneheim and
      Lundman's qualitative content analysis. RESULTS: The results showed that
      conditions for school health nurses' work with health promotion varied between
      the different municipalities. This had an influence on what they did and the
      extent to which they worked in this way. The school health nurses described three
      important aspects that were essential in order to enable successful health
      promotion work in schools: organisation, support and knowledge. Organisation: It
      was important to understand the role of school health nurses and the conditions
      for health promotion work. Without this, they could only work on an individual
      level. Support: A network of other professions, working in close collaboration
      for the health of the pupils, created an understanding of ill health and what
      could be done to promote health. Knowledge: Most school health nurses recognized
      a lack of general theories and methods, leading to different empirical working
      methods in the municipalities. CONCLUSION: In an organisation where the need for
      health promotion work was understood, and school health nurses had support and
      knowledge, health promotion could be performed not only on an individual- but
      also on a general level.

PMID- 19845887
TI  - Ethical dilemmas: a resource in public health nurses' everyday work?
AB  - The aim of this article is to discuss how ethical dilemmas can be a valuable
      resource in public health nurses' parent counselling practice. The discussion is
      based on findings from a study where ten Norwegian public health nurses'
      narratives about their parent counselling practices are analysed. The context
      includes intentions and manuals from a state parent counselling program. The
      study has been approved by Norwegian Social Science Data Services. The narratives
      provide insight into public health nurses' rationale behind choices of actions,
      different roles they identify with and the ethical dilemmas they encounter in
      their everyday work. The ethical dilemmas explicated in the narratives, are
      connected to expectations concerning the content of parent counselling, as well
      as the role of the participants in the counselling sessions. The focus on ethical
      dilemmas that arises through different role-expectations, explicates how public
      health nurses' counselling practices are characterized by a multiplicity of
      voices and discourses. This article shows how a multiple-voiced aspect allows
      public health nurses to change and adjust their practice to meet parents' wishes
      and needs, without being disloyal to what they perceive to be their public
      commission.

PMID- 19845888
TI  - Evidence that self-relevant motives and metaphoric framing interact to influence
      political and social attitudes.
AB  - We propose that metaphor is a mechanism by which motivational states in one
      conceptual domain can influence attitudes in a superficially unrelated domain.
      Two studies tested whether activating motives related to the self-concept
      influences attitudes toward social topics when the topics' metaphoric association
      to the motives is made salient through linguistic framing. In Study 1, heightened
      motivation to protect one's own body from contamination led to harsher attitudes
      toward immigrants entering the United States when the country was framed in body
      metaphoric, rather than literal, terms. In Study 2, a self-esteem threat led to
      more positive attitudes toward binge drinking of alcohol when drinking was
      metaphorically framed as physical self-destruction, compared with when it was
      framed literally or metaphorically as competitive other-destruction.

PMID- 19845889
TI  - Suppressing secrecy through metacognitive ease: cognitive fluency encourages self
      disclosure.
AB  - Understanding when people reveal unfavorable information about themselves is both
      practically and theoretically important. Existing research suggests that people
      tend not to adopt stable disclosure strategies, and consequently disclose too
      much information in some situations (e.g., embarrassing personal information on
      Facebook) and too little in other situations (e.g., risky sexual behavior to a
      physician during diagnosis of a possible sexually transmitted disease). We sought
      to identify a domain-general cue that predicts self-disclosure patterns. We found
      that metacognitive ease, or fluency, promoted greater disclosure, both in tightly
      controlled lab studies (Studies 1a, 1b, and 3) and in an ecologically valid on
      line field study (Study 4). Disfluency tended to prime thoughts and emotions
      associated with risk, which might be one reason why people who experience
      disfluency are less comfortable with self-disclosure (Studies 2 and 3). We
      conclude by discussing the implications of these results for theory and clinical
      practice.

PMID- 19845890
TI  - Construing collective concerns: increasing cooperation by broadening construals
      in social dilemmas.

PMID- 19845891
TI  - Ongoing victim suffering increases prejudice: the case of secondary anti
      semitism.
AB  - Some people have postulated that the perception of Jews' ongoing suffering from
      past atrocities can result in an increase in anti-Semitism. This postulated
      secondary anti-Semitism is compatible with a number of psychological theories,
      but until now there has been no empirical evidence in support of this notion. The
      present study provides the first evidence that ongoing suffering evokes an
      increase in prejudice against the victims. However, this effect became apparent
      only if respondents felt obliged to respond truthfully because of a bogus
      pipeline (BPL); without this constraint, the perception of ongoing victim
      suffering led to a socially desirable reduction in self-reported prejudice. The
      validity of the BPL manipulation was confirmed by the finding that it moderated
      the relation between explicit and implicit anti-Semitism, as measured with an
      affect misattribution procedure.

PMID- 19845892
TI  - In Memoriam: Jean Dausset (1916-2009).

PMID- 19845893
TI  - Plasma concentrations of TNF-alpha and its soluble receptors sTNFR1 and sTNFR2 in
      patients with coronary artery disease.
AB  - Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic
      myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell
      membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim
      of the study was to establish factors associated with plasma concentrations of
      TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since
      adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in
      genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase
      1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma
      concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167
      patients with CAD. Common factors significantly associated with higher TNF-alpha,
      sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher
      BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive
      pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also
      associated with the presence of heart failure (HF), lower ejection and shortening
      fraction, the presence of diabetes or metabolic syndrome, lower serum HDL
      cholesterol, and higher uric acid. In multivariate analysis the common
      independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR,
      lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were
      no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its
      receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2
      reflect the impairment of cardiac and renal function in patients with CAD.
      Metabolic syndrome and diabetes are associated with higher plasma concentrations
      of TNF-alpha and its receptors.

PMID- 19845894
TI  - High-resolution, high-throughput HLA genotyping by next-generation sequencing.
AB  - The human leukocyte antigen (HLA) class I and class II loci are the most
      polymorphic genes in the human genome. Hematopoietic stem cell transplantation
      requires allele-level HLA typing at multiple loci to select the best matched
      unrelated donors for recipient patients. In current methods for HLA typing, both
      alleles of a heterozygote are amplified and typed or sequenced simultaneously,
      often making it difficult to unambiguously determine the sequence of the two
      alleles. Next-generation sequencing methods clonally propagate in parallel
      millions of single DNA molecules, which are then also sequenced in parallel.
      Recently, the read lengths obtainable by one such next-generation sequencing
      method (454 Life Sciences, Inc.) have increased to >250 nucleotides. These clonal
      read lengths make possible setting the phase of the linked polymorphisms within
      an exon and thus the unambiguous determination of the sequence of each HLA
      allele. Here we demonstrate this capacity as well as show that the throughput of
      the system is sufficiently high to enable a complete, 7-locus HLA class I and II
      typing for 24 or 48 individual DNAs in a single GS FLX sequencing run. Highly
      multiplexed amplicon sequencing is facilitated by the use of sample-specific
      internal sequence tags (multiplex identification tags or MIDs) in the primers
      that allow pooling of samples yet maintain the ability to assign sequences to
      specific individuals. We have incorporated an HLA typing software application
      developed by Conexio Genomics (Freemantle, Australia) that assigns HLA genotypes
      for these 7 loci (HLA-A, -B, -C, DRB1, DQA1, DQB1, DPB1), as well as for DRB3,
      DRB4, and DRB5 from 454 sequence data. The potential of this HLA sequencing
      system to analyze chimeric mixtures is demonstrated here by the detection of a
      rare HLA-B allele in a mixture of two homozygous cell lines (1/100), as well as
      by the detection of the rare nontransmitted maternal allele present in the blood
      of a severe combined immunodeficiency disease syndrome (SCIDS) patient.

PMID- 19845895
TI  - Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and
      Hungarian populations.
AB  - Celiac disease is a chronic inflammation of the small intestine, arising in
      genetically predisposed individuals as a result of ingestion of dietary gluten.
      The only confirmed and functionally characterised genetic risk factors for celiac
      disease are the DQ2 or DQ8 heterodimers at the major histocompatibility complex
      (MHC) class II locus (CELIAC1). These genes are necessary but alone not
      sufficient for disease onset. Genome-wide linkage scans have suggested chromosome
      5q31-q33 (CELIAC2) as an important risk locus for celiac disease. This region has
      also been associated to other inflammatory disorders, although as yet, no clear
      gene associations have been found. In the current study, 11 celiac disease
      candidate loci were screened for genetic linkage in the Hungarian population. As
      the CELIAC2 locus showed the strongest evidence for linkage, this locus was
      selected for follow-up. Seventeen candidate genes were selected from the CELIAC2
      locus, and genotyped using 48 haplotype tagging single nucleotide polymorphisms
      (SNPs) in large Finnish and Hungarian family materials. A subset of these, 40
      tagging SNPs in 15 genes, were genotyped in an independent set of Finnish and
      Hungarian cases and controls. We confirmed linkage of this region with celiac
      disease and report strong linkage in both the Finnish and Hungarian populations.
      The association analysis showed modest associations throughout the whole region.
      These association findings were not replicated in the case-control datasets. Our
      study strongly supports the role of the CELIAC2 locus in celiac disease, but it
      also highlights the need for a more powerful study design in the region, to
      locate the true disease risk variants.

PMID- 19845896
TI  - Genetic polymorphisms and haplotype structures of HSPA5 gene in the Han
      population of Southern China.
AB  - The heat shock 70 kDa protein 5 (HSPA5) gene is known to be involved in stress
      associated diseases. In this study, the promoter, exons, 3' untranslated region
      (3'UTR), and subtotal introns of the HSPA5 gene were sequenced in a sub
      population of 161 healthy Han Chinese. Nine single-nucleotide polymorphisms
      (SNPs) including a new one (-86bp T > A from the estimated translation start
      site) were found and 15 haplotypes (frequencies > 1%) were inferred.
      Polymorphisms rs391957 and rs11355458 were completely linked in our population (r
      (2) = 1.00). Using this information, fellow scientists may be able to decrease
      the number of SNPs to be genotyped in future disease case-control studies.

PMID- 19845897
TI  - Five novel HLA-A alleles, HLA-A*030108, A*2491, A*2498, A*330303, A*3317 were
      identified by polymerase chain reaction sequence based typing.
AB  - Five HLA-A variant alleles HLA-A*030108, A*2491, A*2498, A*330303, A*3317 were
      identified in Chinese individuals.

PMID- 19845898
TI  - A novel allele, HLA-A*110203, was identified in a Chinese individual.
AB  - This allele is characterized by a nucleotide substitution (C>T) in exon 4 at
      position nt 672, codon 200 (ACC>ACT), no coding change.

PMID- 19845899
TI  - Identification of a novel HLA-A*680202 allele by sequence-based typing in an
      African American individual.
AB  - The new HLA-A*680202 differs from HLA-A*680201 by one synonymous nucleotide
      substitution at position 618 (ACG --> ACT).

PMID- 19845900
TI  - A novel HLA-B allele, B*4096 was identified by sequence-based typing in a Chinese
      individual.
AB  - A novel HLA-B allele, B*4096, has been identified in a Chinese individual by
      sequence-based typing, which has seven nucleotide changes from the closest
      matching allele B*40060101 resulting in five amino acid changes: 101Ser-->Asn;
      104Ser-->Thr; 105Leu-->Ala; 106Arg--> Leu and 107Gly-->Arg.

PMID- 19845901
TI  - A novel HLA-B*54 allele, B*5417, identified in a Northern Chinese Han individual.
AB  - The full-length sequence of HLA-B*5417 differs from HLA-B*5401 only by single
      nucleotide change at nt 709 where A-->C resulting in a amino acid substitution
      from Ile (ATC) to Val (GTC) at codon 213 in exon 4.

PMID- 19845902
TI  - A novel HLA-B allele: HLA-B*5419.
AB  - B*5419 differs from B*5401 by a single nucleotide substitution at codon 13 (TCC -
      > TTC).

PMID- 19845903
TI  - A frame shift due to a two-nucleotide deletion results in an HLA-B null allele,
      B*9549N.
AB  - This report describes the identification of a new human leukocyte antigen (HLA)
      class I null allele, B*9549N, resulting from a premature stop codon in exon 3.

PMID- 19845904
TI  - Identification of a novel HLA-Cw*070206 allele.
AB  - The novel HLA-Cw*070206 allele differs from the closest allele Cw*07020101 by
      single nucleotide change at genomic DNA nt 877 C>T (codon 143 ACC > ACT) in exon
      3.

PMID- 19845905
TI  - Cloning and sequencing analysis of a novel HLA-Cw*08 variant allele, Cw*0827.
AB  - The novel HLA-Cw*0827 variant allele differs from the closest allele Cw*0802 by
      five nucleotide changes.

PMID- 19845906
TI  - The predicted protein structures of the novel DRB1*0717 and DRB1*0701 are highly
      related.
AB  - This article describes the identification of the novel human leukocyte antigen
      (HLA) allele DRB1*07 7 that was detected in a potential stem-cell donor of
      Caucasian origin. Compared to DRB1*070101, the new allele is characterized by a
      nonsynonymous nucleotide exchange of C-->T at position 201 in exon 2 replacing
      Arg by Trp in codon 72. As this sequence variation has not been seen earlier in
      any other HLA-DRB allele, it is most probably the result of a point mutation.

PMID- 19845907
TI  - The novel HLA-G*01010302 allele differs from G*01010301 by a single nucleotide
      change in intron 5.
AB  - HLA-G*01010301 and G*01010302 differ by a single point mutation in intron 5.

PMID- 19845909
TI  - Identification of the HLA-Cw*0774 and DQB1*060105 alleles.
AB  - Cw*0774 differs from Cw*070201 by one nucleotide within the coding sequence of
      exons 2-4. DQB1*060105 differs from DQB1*060101 by one nucleotide within the
      coding sequence of exons 2-3.

PMID- 19845910
TI  - IL-21: roles in immunopathology and cancer therapy.
AB  - Cytokines are secreted signalling molecules with decisive effects on
      haematopoiesis, innate and adaptive immunity, and immunopathology. Interleukin
      (IL)-21 is a novel cytokine produced by activated CD4(+) T cells and natural
      killer T (NKT) cells. IL-21 is part of a family of cytokines which include IL-2, 
      4, -7, -9 and -15 that all share the common IL-2 receptor gamma chain (gamma(c))
      in their individual receptor complexes. IL-21 receptor (IL-21R) is widely
      expressed on both myeloid and lymphoid cell lineages and IL-21 actions include co
      stimulation of B cell differentiation and immunoglobulin (Ig) production, co
      mitogen of T cells, and stimulation of NK and CD8(+) T cell cytotoxic function.
      Initially, IL-21 was recognized for its anti-tumour effects in several
      preclinical tumour models, warranting its currently ongoing clinical development
      as a cancer immunotherapeutic. More recently, IL-21 has been associated with the
      development of a panel of autoimmune and inflammatory diseases, where
      neutralization of IL-21 has been suggested as a potential new therapy. In this
      review, we will cover the latest discoveries of IL-21 as a cancer therapy and its
      implications in immunopathologies.

PMID- 19845911
TI  - A high-throughput Taqman approach for the discrimination of HLA-E alleles.
AB  - An association between human leukocyte antigen (HLA) molecules and the incidence
      of various diseases has been recognized for years. Molecules of the HLA system
      also exert an important role on the clinical outcome after transplantation such
      as stem cell transplantation. The conventional HLA typing method is sequence
      based typing (SBT) which is reliable but laborious. The goal of this study was to
      develop a high-throughput Taqman assay to screen large panels for HLA-E alleles.
      Two functional HLA-E alleles, *0101 and *0103, have been identified. We set up
      the Taqman assay with genomic DNA as template to discriminate the three HLA-E
      genotypes: homozygous HLA-E*0101, heterozygous *0101, *0103 and homozygous *0103.
      This Taqman approach was validated by the comparison of results obtained with the
      typing results acquired by sequenced base typing (SBT). Additional screening of a
      large panel showed the pronounced discriminative capacity of the Taqman assay for
      HLA-E allele typing. The Taqman assay is a fast, reliable and consistent HLA-E
      allele typing method, especially useful to screen large panels.

PMID- 19845912
TI  - A novel HLA-Cw*0124 allele found in a Chinese Han patient from Southern China.
AB  - The sequence of novel HLA-Cw*0124 allele differs from Cw*0103 by one nucleotide
      change at nt 806 from C to A, resulting in an amino acid change at codon 245 from
      Ala to Glu.

PMID- 19845913
TI  - Interaction of functional FCER2 promoter polymorphism and phenotype-associated
      haplotypes.
AB  - Low-affinity IgE receptor gene (FCER2) rs3760687 polymorphism was found to be
      associated with differential binding affinity of transcription factors Sp1 and
      Sp3 leading to altered transcriptional activity. Haplotypic interaction of
      functional FCER2 polymorphisms (rs28364072, rs2228137 and rs3760687) might
      potentially provide a background for genotype-phenotype associations previously
      observed for some rather non-functional FCER2 variants.

PMID- 19845914
TI  - Three new HLA-B alleles determined by sequence-based typing: B*9551, B*5161 and
      B*5317.
AB  - Three new alleles with polymorphisms located in exons 2 and 3.

PMID- 19845915
TI  - Molecular variation at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci in full
      heritage American Indians in Arizona: private haplotypes and their evolution.
AB  - A sample of 492 full heritage, unrelated residents of the Gila River Indian
      Community (GRIC) of Arizona were characterized for their high-resolution DNA
      alleles at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci. Only five allelic
      categories are found at HLA-A, 10 at HLA-B, 8 at HLA-C and HLA-DR, and 4 at DQA1
      and DQB1. There is little evidence for population structure at the 6 loci. Two
      'private' alleles, B*5102 and B*4005, which are found nearly exclusively in
      American Indian populations in the desert southwest and northern Mexico, are
      likely new mutations after the first inhabitation of the area, the evolution of
      which are reflected in the contemporary distribution of their respective
      haplotypes. DRB1*1402 has the highest reported frequency of any specificity at
      the DRB1 locus, 0.7461, and serves as a sensitive probe for locating related east
      Asian populations. The haplotypes in this population also exhibit a highly
      restricted distribution and strong genetic disequilibria, which has important
      implications for matching solid organ and bone marrow allografts. It is shown
      that, when one considers HLA-A-B-DRB1 homozygotes as allograft donors for all
      full heritage members of the GRIC, 50% of the community would find a non
      mismatched organ within the homozygotes for the six most common haplotypes. This
      raises questions about transplantation policy and whether, in the presence of
      high-frequency private alleles and a restricted number of haplotypes, the full
      heritage American Indian community of the desert southwest should act as its own
      pool of donors for its affected members.

PMID- 19845916
TI  - Four-locus high-resolution HLA typing in a sample of Mexican Americans.
AB  - Mexicans are the most common minority population of the United States. From a
      sample of 553 bone marrow donor registrants of self-described Mexican ancestry,
      human leukocyte antigen (HLA) loci A, C, B and DRB1 were typed by high resolution
      sequence based typing (SBT) methods. A total of 47, 34, 76 and 46 distinct
      alleles at A, C, B and DRB1 respectively were identified, including 3 new
      alleles. The four-locus haplotype frequency distribution was extremely skewed
      with only 53.9% of 1106 chromosomes present with more than one estimated copy.
      Haplotypes of Native American origin were identified. These data form an initial
      basis for determining the requirements for an adequate donor pool for stem cell
      transplantation in this population.

PMID- 19845917
TI  - Full length sequence of the HLA-Cw*0361 allele identified in a Chinese Han
      potential bone marrow donor from Northern China.
AB  - HLA-Cw*0361 allele differs from Cw*030301 by one nucleotide substitution at nt
      566 from T to A, resulting in an amino acid change at codon 165 from Val to Glu.

PMID- 19845919
TI  - A conserved, lipid-mediated sorting mechanism of yeast Ist2 and mammalian STIM
      proteins to the peripheral ER.
AB  - Sorting of yeast Ist2 to the plasma membrane (PM) or the cortical endoplasmic
      reticulum (ER) requires a cortical sorting signal (CSS(Ist2)) that interacts with
      lipids including phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) at the PM.
      Here, we show that the expression of Ist2 in mammalian cells resulted in a
      peripheral patch-like localization without any detection of Ist2 at the cell
      surface. Attached to C-termini of mammalian integral membrane proteins, the
      CSS(Ist2) targeted these proteins to PM-associated domains of the ER and
      abolished trafficking via the classical secretory pathway. The interaction of
      integral membrane proteins with PI(4,5)P(2) at the PM created ER-PM contacts.
      This process is similar to the regulated coupling of ER domains to the PM via
      stromal interaction molecule (STIM) proteins during store-operated Ca(2+) entry
      (SOCE). The CSS(Ist2) and the C-terminus of the ER-located Ca(2+) sensor STIM2
      were sufficient to bind PI(4,5)P(2) and PI(3,4,5)P(3) at the PM, showing that an
      evolutionarily conserved mechanism is involved in the sorting of integral
      membrane proteins to PM-associated domains of the ER. Yeast Ist2 and STIM2 share
      a common basic and amphipathic signal at their extreme C-termini. STIM1 showed
      binding preference for liposomes containing PI(4,5)P(2), suggesting a specific
      contribution of lipids to the recruitment of ER domains to the PM during SOCE.

PMID- 19845920
TI  - The social reality of migrant men with tuberculosis in Kathmandu: implications
      for DOT in practice.
AB  - OBJECTIVE: To establish which of the many possible linkages between tuberculosis
      (TB), direct observation of treatment (DOTS), and the social reality of migrant
      workers in Kathmandu are the most relevant to the health outcomes and economic
      and social well-being of these populations, and which are amenable to possible
      interventions and high-yield policy changes. METHODS: Fourteen semi-structured in
      depth interviews were conducted through an interpreter with male migrant TB
      patients aged 18-50 years recruited from three DOTS clinics in the Kathmandu
      valley in May 2005. The interviews were coded using constant comparison and
      analysed using a grounded theory method. RESULTS: The economic burden of TB
      treatment is far greater than the financial reserve of migrants. Consequently
      remittances sent to families are reduced and migrants remain in debt long after
      treatment completion, tied to the treatment location paying off high interest
      loans. Forced to attend clinics far away from their home, and isolated by the
      stigma associated with TB, migrants are vulnerable without social support
      networks. Migrants find that daily clinic visits are incompatible with working
      schedules and important cultural festivals, which forces them into defaulting.
      CONCLUSION: The needs of migrant workers with TB living in Kathmandu are not
      being adequately met. Current service provision needs to be reviewed to build in
      greater flexibility and support for migrant men.

PMID- 19845918
TI  - Regulation of insulin secretion by phosphatidylinositol-4,5-bisphosphate.
AB  - The role of PIP(2) in pancreatic beta cell function was examined here using the
      beta cell line MIN6B1. Blocking PIP(2) with PH-PLC-GFP or PIP5KIgamma RNAi did
      not impact on glucose-stimulated secretion although susceptibility to apoptosis
      was increased. Over-expression of PIP5KIgamma improved cell survival and
      inhibited secretion with accumulation of endocytic vacuoles containing F-actin,
      PIP(2), transferrin receptor, caveolin 1, Arf6 and the insulin granule membrane
      protein phogrin but not insulin. Expression of constitutively active Arf6 Q67L
      also resulted in vacuole formation and inhibition of secretion, which was
      reversed by PH-PLC-GFP co-expression. PIP(2) co-localized with gelsolin and F
      actin, and gelsolin co-expression partially reversed the secretory defect of
      PIP5KIgamma-over-expressing cells. RhoA/ROCK inhibition increased actin
      depolymerization and secretion, which was prevented by over-expressing
      PIP5KIgamma, while blocking PIP(2) reduced constitutively active RhoA V14-induced
      F-actin polymerization. In conclusion, although PIP(2) plays a pro-survival role
      in MIN6B1 cells, excessive PIP(2) production because of PIP5KIgamma over
      expression inhibits secretion because of both a defective Arf6/PIP5KIgamma
      dependent endocytic recycling of secretory membrane and secretory membrane
      components such as phogrin and the RhoA/ROCK/PIP5KIgamma-dependent perturbation
      of F-actin cytoskeleton remodelling.

PMID- 19845923
TI  - Propofol and fentanyl infusions in dogs of various breeds undergoing surgery.
AB  - OBJECTIVE: To report the cardiovascular variables, anaesthetic effects and
      recovery quality of an anaesthesia technique using variable rate infusion
      propofol combined with constant rate infusion fentanyl in dogs undergoing
      elective surgery. Study design Prospective clinical trial. ANIMALS: A total of 27
      dogs, aged 2.7 +/- 2.65 years and weighing 24 +/- 11 kg. METHODS: Following
      intramuscular acepromazine (0.03 or 0.05 mg kg(-1)) and subcutaneous carprofen (4
      mg kg(-1)) pre-medication, anaesthesia was induced with propofol (4.0 +/- 0.5 mg
      kg(-1)) intravenously (IV). All dogs were ventilated with 100% oxygen to maintain
      normocapnia. Propofol was infused at 0.4 mg kg(-1) minute(-1) for 20 minutes and
      then at 0.3 mg kg(-1 )minute(-1). If mean arterial blood pressure (MAP) decreased
      below 70 mmHg, propofol infusion was reduced by 0.1 mg kg(-1) minute(-1). Five
      minutes after induction of anaesthesia, fentanyl was administered (2 microg kg(
      1)) IV followed by the infusion at 0.5 microg kg(-1) minute(-1) and atropine (40
      microg kg(-1)) IV. Heart rate, MAP, respiratory rate, tidal volume, end-tidal
      carbon dioxide, presence of reflexes, movements and recovery times and quality
      were recorded. RESULTS: Mean anaesthetic duration was 131 +/- 38.5 minutes. Mean
      heart rate peaked 10 minutes after atropine injection and gradually declined,
      reaching pre-anaesthetic values at 55 minutes. MAP easily was maintained above 70
      mmHg. Mean times to return of spontaneous ventilation, extubation, head lift and
      sternal recumbency were 21 +/- 10.1, 33 +/- 14.6, 43 +/- 19.7 and 65 +/- 23.4
      minutes, respectively. Recovery was smooth and quiet. The time to sternal
      recumbency was significantly correlated with the duration of anaesthesia and
      total dose of propofol; time to extubation was correlated to total dose of
      propofol. CONCLUSION AND CLINICAL RELEVANCE: Propofol and fentanyl infusions
      provided stable cardiovascular function and satisfactory conditions for surgery.
      Some modifications of infusion rates are required to improve the long-recovery
      times.

PMID- 19845921
TI  - Pneumonia among young infants in rural Southeast Asia (Bohol Island,
      Philippines).
AB  - OBJECTIVE: To develop a clinical algorithm that can be used to identify pneumonia
      deaths in young infants in developing countries and estimate the disease burden
      in this population. PATIENTS AND METHODS: Infants younger than 60 days
      hospitalized with signs of severe pneumonia who underwent clinical, microbiologic
      and radiological evaluation were the subjects. Stepwise logistic regression and
      subtractive iterative process were used to derive the algorithm. RESULTS: Three
      hundred and one infants had either clinical or radiographic pneumonia. The case
      fatality rate for 185 infants with radiographic pneumonia was 21%vs. 5% for
      clinical pneumonia. Age below 7 days was associated with an increased risk of
      dying. Among 7- to 59-day-old infants, poor feeding, cyanosis and absence of
      crackles were predictors of death from pneumonia. Using logistic regression, an
      algorithm consisting of any one of three clinical signs (cyanosis, poor feeding
      and abnormally sleepy) was developed in infants aged 7-59 days; 80% of deaths and
      50% of those with radiographic pneumonia have at least one of these signs. It
      performed better than both the WHO case management algorithm and the IMCI
      algorithm. CONCLUSION: Radiographic pneumonia is a common and serious infection
      among infants below 2 months old in the Philippines. Cyanosis, poor feeding and
      abnormal sleepiness are simple signs that can be used by health workers to
      identify seriously ill infants who are most likely to die from pneumonia.

PMID- 19845924
TI  - A comparison of the effects of two different doses of ketamine used for co
      induction of anaesthesia with a target-controlled infusion of propofol in dogs.
AB  - OBJECTIVE: To assess the cardiorespiratory and hypnotic-sparing effects of
      ketamine co-induction with target-controlled infusion of propofol in dogs. STUDY
      DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: Ninety healthy
      dogs (ASA grades I/II). Mean body mass 30.5 +/- SD 8.6 kg and mean age 4.2 +/-
      2.6 years. METHODS: All dogs received pre-anaesthetic medication with
      acepromazine (0.03 mg kg(-1)) and morphine (0.2 mg kg(-1)) administered
      intramuscularly 30 minutes prior to induction of anaesthesia. Heart rate and
      respiratory rate were recorded prior to pre-medication. Animals were allocated
      into three different groups: Group 1 (control) received 0.9% NaCl, group 2, 0.25
      mg kg(-1) ketamine and group 3, 0.5 mg kg(-1) ketamine, intravenously 1 minute
      prior to induction of anaesthesia, which was accomplished using a propofol target
      controlled infusion system. The target propofol concentration was gradually
      increased until endotracheal intubation was possible and the target concentration
      at intubation was recorded. Heart rate, respiratory rate and noninvasive blood
      pressure were recorded immediately prior to induction, at successful intubation
      and at 3 and 5 minutes post-intubation. The quality of induction was graded
      according to the amount of muscle twitching and paddling observed. Data were
      analysed using a combination of chi-squared tests, Fisher's exact tests, Kruskal
      Wallis, and anova with significance assumed at p < 0.05. RESULTS: There were no
      significant differences between groups in the blood propofol targets required to
      achieve endotracheal intubation, nor with respect to heart rate, noninvasive
      blood pressure or quality of induction. Compared with the other groups, the
      incidence of post-induction apnoea was significantly higher in group 3, but
      despite this dogs in this group had higher respiratory rates overall. CONCLUSIONS
      AND CLINICAL RELEVANCE: Under the conditions of this study, ketamine does not
      seem to be a useful agent for co-induction of anaesthesia with propofol in dogs.

PMID- 19845925
TI  - The effect of pre-anaesthetic fasting time and type of food on gastric content
      volume and acidity in dogs.
AB  - OBJECTIVE: To investigate the effect of pre-anaesthetic fasting time and variety
      of food on gastric content (GC) volume and pH in dogs. STUDY DESIGN: Randomized,
      cross-over, prospective experimental study. ANIMALS: Fifteen mongrel dogs (nine
      females and six males 1-4 years old, weighing 10-24.5 kg). METHODS: Each dog
      received the same seven treatments in random order: dry food 3 hours before
      anaesthesia (BA) (treatment 3D), canned food (half daily rate) 3 hours BA
      (treatment 3C), 0% fat cow milk 3 hours BA (treatment 3M), dry food 10 hours BA
      (treatment 10D), canned food 10 hours BA (treatment 10C), low fat canned food 10
      hours BA (treatment 10F) and low protein canned food 10 hours BA (treatment 10P).
      All animals were pre-medicated with propionyl promazine and anaesthesia was
      induced with thiopental sodium and maintained with halothane. GC was aspirated
      using an orogastric catheter and its volume and pH were measured. RESULTS:
      Treatment 10F had significantly lower GC pH than all the 3-hour treatments.
      Treatments 10D and 10P had significantly lower pH than treatments 3D and 3C.
      Treatment 3M had significantly lower pH than the other 3-hour treatments.
      Treatment 3D had significantly greater gastric volume than treatments 3M, 10C,
      10F and 10P. CONCLUSIONS AND CLINICAL RELEVANCE: Canned food at half the daily
      rate administered 3 hours before anaesthesia did not increase significantly the
      GC volume compared to the other types of food used. The GC pH was also high. This
      type of food fed 3 hours before induction of anaesthesia may be of benefit in
      reduction of the incidence of gastro-oesophageal reflux during anaesthesia in
      dogs.

PMID- 19845926
TI  - Gastro-oesophageal reflux during anaesthesia in the kitten: comparison between
      use of a laryngeal mask airway or an endotracheal tube.
AB  - OBJECTIVE: To compare the incidence of gastro-oesophageal reflux (GOR) during
      anaesthesia in the kitten when using a laryngeal mask airway (LMA) or an
      endotracheal tube (ET). STUDY DESIGN: Prospective randomized cross-over
      experimental study. ANIMALS: Forty Domestic Short Hair laboratory cats, 19
      females and 21 males, aged 12-15 weeks and weighing 0.57-1.73 kg (mean 1.13 +/-
      SD 0.26). METHODS: Kittens were anaesthetized twice, once using the LMA and once
      the ET. Following induction of anaesthesia with isoflurane in an anaesthetic
      chamber and intubation of the trachea with the ET or placement of the LMA, a pH
      electrode was introduced into the lower oesophagus. Monitoring of the oesophageal
      pH was performed for 45 minutes while anaesthesia was maintained with isoflurane.
      At the end of the experiment, gastric pH was measured. Kittens that had GOR
      during the experiment were treated with sucralfate, cisapride and ranitidine for
      15 days. Results Oesophageal pH was 6.51 +/- 0.76 and gastric pH was 1.54 +/-
      0.59. GOR was observed in nine kittens when the ET was used, and in 20 kittens
      when the LMA was used, the difference being significant (p = 0.013). The
      refluxate nearly always was acidic, being alkaline in only one kitten. Most of
      the GOR episodes occurred shortly after induction of anaesthesia and the
      oesophageal pH remained below 4.0 until the end of the experiment. No
      regurgitation was observed. CONCLUSIONS AND CLINICAL RELEVANCE: The use of the
      LMA is associated with an increased incidence of GOR during anaesthesia in the
      kitten, which is not detected by observation. That this may have occurred should
      be considered if the kitten demonstrates signs of oesophagitis in the
      postoperative period.

PMID- 19845927
TI  - Plasma lactate concentrations in free-ranging moose (Alces alces) immobilized
      with etorphine.
AB  - OBJECTIVE: To investigate plasma lactate concentrations of etorphine-immobilized
      moose in relation to environmental, temporal and physiological parameters. STUDY
      DESIGN: Prospective clinical study. ANIMALS: Fourteen female and five male moose
      (Alces alces), estimated age range 1-7 years. METHODS: The moose were darted from
      a helicopter with 7.5 mg etorphine per animal using projectile syringes and a
      dart gun. Once immobilized, the moose were approached, a venous blood sample was
      obtained and vital signs including pulse oximetry were recorded. Diprenorphine
      was administered to reverse the effects of etorphine. Timing of events, ambient
      temperature and snow depth were recorded. Blood samples were cooled and
      centrifuged before plasma was harvested and frozen. The plasma was thawed later
      and lactate analysed. Data were analysed using descriptive statistics and
      regression analysis. RESULTS: All animals recovered uneventfully and were alive
      12 weeks after immobilization. Mean +/- SD plasma lactate was found to be 9.2 +/-
      2.1 mmol L(-1). Plasma lactate concentrations were related positively to snow
      depth and negatively to time from induction of immobilization to blood sampling.
      The model that best described the variability in plasma lactate concentrations
      used induction time (time from firing the dart to the moose being immobilized).
      The second best model included induction time and snow depth. CONCLUSIONS AND
      CLINICAL RELEVANCE: Plasma lactate concentrations in these etorphine-immobilized
      moose were in the range reported for other immobilized wild ruminants. Decreasing
      induction time, which may be related to a more profound etorphine effect, and
      increasing snow depth possibly may increase plasma lactate concentrations in
      etorphine-immobilized moose.

PMID- 19845928
TI  - Tramadol improved the efficacy of ketamine-xylazine anaesthesia in young pigs.
AB  - OBJECTIVE: To evaluate the influence of premedication with tramadol on xylazine
      ketamine anaesthesia in young pigs. STUDY DESIGN: Prospective, randomized,
      blinded cross-over study. ANIMALS: Ten young Niger hybrid pigs: mean weight 6.1
      +/- 0.6 kg. METHODS: Pigs were anaesthetized twice. Xylazine (2.5 mg kg(-1)),
      ketamine (25 mg kg(-1)) and atropine (0.04 mg kg(-1)) were administered by
      intramuscular (IM) injection, 5 minutes after either tramadol (5 mg kg(-1)))
      (treatment XKT) or saline (treatment XKS). Time to loss of righting reflex
      (TLRR), duration of antinociception, duration of recumbency (DR) and recovery
      times (RCT) were recorded. Quality of induction of anaesthesia including ease of
      endotracheal intubation was assessed using a subjective ordinal rating score of 1
      (worst) to 4 (best). Heart, pulse and respiratory rates, arterial oxygen
      saturations and rectal temperatures were determined over 60 minutes.
      Antinociception was assessed by the pigs' response to artery forceps applied at
      the interdigital space. Data were compared with Student's t-test, Mann-Whitney's
      test or analysis of variance (anova) for repeated measures as appropriate and are
      presented as mean +/- standard deviation. RESULTS: The quality of anaesthetic
      induction was significantly better and duration of antinociception significantly
      longer (p < 0.05) in treatment XKT (3.1 +/- 0.7 score; 43.7 +/- 15.5 minutes)
      than in treatment XKS (2.8 +/- 0.6 score; 32.0 +/- 13.3 minutes). TLRR, DR and
      RCT did not differ significantly (p > 0.05) between treatment XKT (2.1 +/- 0.8,
      65.8 +/- 17.0 and 13.2 +/- 6.7 minutes) and treatment XKS (2.1 +/- 1.3, 58.0 +/-
      14.8 and 10.3 +/- 5.6 minutes). Physiological measurements did not differ between
      the treatments. CONCLUSION AND CLINICAL RELEVANCE: Tramadol improved the quality
      of anaesthetic induction and increased the duration of antinociception in
      xylazine-ketamine anaesthetized young pigs without increasing duration of
      anaesthesia, nor causing additional depression of the physiological parameters
      measured.

PMID- 19845929
TI  - Acute noncardiogenic pulmonary edema in an anesthetized Nubian goat kid.
AB  - OBSERVATIONS: A 1-month-old Nubian goat presented for sialocyst resection.
      Physical examination and bloodwork were unremarkable. While pre-oxygenating, the
      goat was sedated with midazolam and morphine (0.1 mg kg(-1) each) intravenously
      (IV). General anesthesia was induced 5 minutes later with 1.7 mg kg(-1) propofol.
      Sevoflurane was administered in oxygen without assisted ventilation via a cuffed
      orotracheal tube. Throughout the first 85 minutes of anesthesia, the goat was
      well-oxygenated (SpO(2), > or =97%), ventilating adequately (Pe'CO(2), 36-48
      mmHg), and had normal mean arterial blood pressure (MAP, 60-85 mmHg). Blood-gas
      values at 45 minutes were consistent with adequate ventilation on oxygen. At 75
      minutes, the goat moved in response to surgical stimulation, requiring additional
      propofol (0.4 mg kg(-1)). After 10 minutes, MAP dropped precipitously to 40 mmHg
      and frequent multiform premature ventricular contractions (PVCs) were observed.
      Crystalloids, hetastarch, and dopamine (5 mug kg(-1) minute(-1)) were
      administered to correct the hypotension. Arterial blood-gas analysis revealed
      that the goat had become hypoxemic (PaO(2), 50 mmHg). Intermittent positive
      pressure ventilation (IPPV) was initiated. Subsequent blood-gas analysis did not
      show significant improvement in PaO(2) (53 and 56 mmHg, respectively). Occasional
      PVCs were observed thereafter. Surgery ended, and sevoflurane and IPPV were
      discontinued. The goat was extubated within 7 minutes and received 100% oxygen by
      mask. Diffuse crackles were ausculted over both hemithoraces. Suspecting
      pulmonary edema, furosemide (1 mg kg(-1)) was administered IV. Radiographs taken
      immediately post-operatively revealed a severe, caudodorsal airspace (alveolar)
      pattern, confirming the diagnosis. Respiration improved considerably within an
      hour with nasal oxygen and two additional doses of furosemide. CONCLUSIONS: The
      goat developed acute, drug-induced, noncardiogenic pulmonary edema in response to
      the second dose of propofol.

PMID- 19845930
TI  - Pharmacokinetics of single-dose oral pregabalin administration in normal dogs.
AB  - OBJECTIVE: To describe the pharmacokinetics of pregabalin in normal dogs after a
      single oral dose. STUDY DESIGN: Prospective experiment. ANIMALS: Six adult
      Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6-5.6) years old
      (median and range) weighing 33.4 (26.8-42.1) kg. METHODS: After jugular vein
      catheterization, the dogs received a single oral dose of pregabalin (
      approximately 4 mg kg(-1)). Blood samples were collected at: 0 (before drug
      administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36
      hours after drug administration. Plasma pregabalin concentration was measured by
      HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables.
      RESULTS: No adverse effects were observed. The median (range) pharmacokinetic
      parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5-92.1)
      microg hour mL(-1); absorption half-life = 0.38 (0.25-1.11) hours; elimination
      half-life = 6.90 (6.21-7.40) hours; time over 2.8 microg mL(-1) (the presumed
      minimal effective concentration) = 11.11 (6.97-14.47) hours; maximal plasma
      concentration (C(max)) = 7.15 (4.6-7.9) microg mL(-1); time for C(max) to occur =
      1.5 (1.0-4.0) hours. Assuming an 8-hour dosing interval, predicted minimal,
      average, and maximal steady state plasma concentrations were 6.5 (4.8-8.1), 8.8
      (7.3-10.9), and 13.0 (8.8-15.2) microg mL(-1). The corresponding values assuming
      a 12-hour interval were 3.8 (2.4-4.8), 6.8 (4.9-7.9), and 10.1 (6.6-11.6) microg
      mL(-1). CONCLUSIONS AND CLINICAL RELEVANCE: Pregabalin 4 mg kg(-1) PO produces
      plasma concentrations within the extrapolated therapeutic range from humans for
      sufficient time to suggest that a twice daily dosing regime would be adequate.
      Further study of the drug's safety and efficacy for the treatment of neuropathic
      pain and seizures in dogs is warranted.

PMID- 19845931
TI  - Intravenous tramadol: effects, nociceptive properties, and pharmacokinetics in
      horses.
AB  - OBJECTIVE: To determine the optimal dose, serum concentrations and analgesic
      effects of intravenous (IV) tramadol in the horse. STUDY DESIGN: Two-phase
      blinded, randomized, prospective crossover trial. ANIMALS: Seven horses (median
      age 22.5 years and mean weight 565 kg). METHODS: Horses were treated every 20
      minutes with incremental doses of tramadol HCl (0.1-1.6 mg kg(-1)) or with
      saline. Heart rate, respiratory rate, step frequency, head height, and sweating,
      trembling, borborygmus and head nodding scores were recorded before and up to 6
      hours after treatment. In a second study, hoof withdrawal and skin twitch reflex
      latencies (HWRL and STRL) to a thermal stimulus were determined 5 and 30 minutes,
      and 1, 2, 4 and 6 hours after bolus IV tramadol (2.0 mg kg(-1)) or vehicle. Blood
      samples were taken to determine pharmacokinetics. RESULTS: Compared to saline,
      tramadol caused no change in heart rate, step frequency or sweating score.
      Respiratory rate, head height, and head nodding and trembling scores were
      transiently but significantly increased and borborygmus score was decreased by
      high doses of tramadol. Following cumulative IV administration of 3.1 mg kg(-1)
      and bolus IV administration of 2 mg kg(-1), the elimination half-life of tramadol
      was 1.91 +/- 0.33 and 2.1 +/- 0.9 hours, respectively. Baseline HWRL and STRL
      were 4.16 +/- 1.0 and 3.06 +/- 0.99 seconds, respectively, and were not
      significantly prolonged by tramadol. CONCLUSION AND CLINICAL RELEVANCE: IV
      tramadol at cumulative doses of up to 3.1 mg kg(-1) produced minimal transient
      side effects but 2.0 mg kg(-1) did not provide analgesia, as determined by
      response to a thermal nociceptive stimulus.

PMID- 19845932
TI  - Atipamezole changes the antinociceptive effects of butorphanol after medetomidine
      ketamine anaesthesia in rats.
AB  - OBJECTIVE: To investigate the effects of atipamezole administered before
      butorphanol, on tail-flick latency (TFL) and also following medetomidine-ketamine
      anaesthesia in rats. STUDY DESIGN: Prospective, randomized experimental study.
      ANIMALS: Thirty-four adult male Sprague-Dawley rats weighing 260-390 g. METHODS:
      TFL in 50 degrees C water was used to measure antinociception. In the first
      experiment, rats received saline (n = 5) or atipamezole (n = 5) followed by
      butorphanol treatments. In the second experiment, three groups of rats received
      saline (n = 8), atipamezole (n = 8) or atimpamezole (n = 8) followed by
      butorphanol 60 minutes after medetomidine-ketamine administration. RESULTS: In
      the first experiment, butorphanol significantly increased TFL compared to
      baseline. Atipamezole significantly decreased this effect. In the second
      experiment, TFL was significantly increased after recovery from medetomidine
      ketamine anaesthesia compared to baseline. This was almost completely blocked by
      atipamezole. Atipamezole with butorphanol after recovery from the anaesthesia
      significantly reduced TFL compared to saline but still significantly increased
      TFL compared to the baseline. CONCLUSION AND CLINICAL RELEVANCE: Atipamezole
      attenuated the analgesic effects of butorphanol. When postoperative atipamezole
      is used to hasten recovery from anaesthesia in rats, it may interfere with the
      postoperative analgesic effect of butorphanol.

PMID- 19845933
TI  - Use of wound soaker catheters for the administration of local anesthetic for post
      operative analgesia: 56 cases.
AB  - OBJECTIVE: To describe the administration of local anesthetic through wound
      soaker catheters for post-operative veterinary patients and to characterize
      complications. STUDY DESIGN: Retrospective study of hospital records. ANIMALS:
      Records of patients in which a wound soaker catheter was placed post-operatively
      between November 1, 2004 and July 1, 2006 at a veterinary teaching hospital.
      Records in which a limb amputation was performed between January 1, 2002 and
      August 1, 2007 and in which a wound soaker catheter was not placed were reviewed
      for historic control. RESULTS: A total of 56 cases were identified in which a
      wound soaker catheter was placed post-operatively including 52 dogs, 2 cats, and
      2 goats. Twenty canine cases were identified in which limb amputation was
      performed and no wound soaker catheter was placed. The majority of surgical
      procedures for which a wound soaker catheter was placed included thoracic limb
      amputation (46.4%) and pelvic limb amputation (35.7%). Wound soaker catheters
      remained in place for an average of 1.6 +/- 0.5 days. Feline and caprine patients
      received intermittent bupivacaine boluses every 6 hours. Canine patients received
      continuous lidocaine infusions. Complications included disconnection of the
      catheter from the infusion (7.7%), one seroma, and one suspected lidocaine
      neurotoxicity. Incisional infections were noted in 3/56 (5.3%) limb amputations
      with wound soaker catheters placed which was not higher than the incisional
      infection rate found in the historic control cases 3/20 (15%). CONCLUSION AND
      CLINICAL RELEVANCE: Use of the wound soaker catheter was a viable means of
      providing local analgesia in post-operative veterinary patients. Studies are
      needed to evaluate efficacy of pain management, and to further investigate
      techniques for catheter placement and maintenance which may help to optimize the
      analgesia achieved using this technique.

PMID- 19845934
TI  - What is your diagnosis? Peritoneal fluid from a dog with epistaxis. Plasma cell
      neoplasia with giant myeloma cells.

PMID- 19845935
TI  - Strategies for translating knowledge into practice.

PMID- 19845936
TI  - The relationship of bottle feeding and other sucking behaviors with speech
      disorder in Patagonian preschoolers.
AB  - BACKGROUND: Previous studies have shown that children's nonnutritive sucking
      habits may lead to delayed development of their oral anatomy and functioning.
      However, these findings were inconsistent. We investigated associations between
      use of bottles, pacifiers, and other sucking behaviors with speech disorders in
      children attending three preschools in Punta Arenas (Patagonia), Chile. METHODS:
      Information on infant feeding and sucking behaviors, age starting and stopping
      breast- and bottle-feeding, pacifier use, and other sucking behaviors, was
      collected from self-administered questionnaires completed by parents. Evaluation
      of speech problems was conducted at preschools with subsequent scoring by a
      licensed speech pathologist using age-normative standards. RESULTS: A total of
      128 three- to five-year olds were assessed, 46% girls and 54% boys. Children were
      breastfed for an average of 25.2 (SD 9.6) months and used a bottle 24.4 (SD 15.2)
      months. Fifty-three children (41.7%) had or currently used a pacifier for an
      average of 11.4 (SD 17.3) months; 23 children (18.3%) were reported to have
      sucked their fingers. Delayed use of a bottle until after 9 months appeared to be
      protective for subsequent speech disorders. There was less than a one-third lower
      relative odds of subsequent speech disorders for children with a delayed use of a
      bottle compared to children without a delayed use of a bottle (OR: 0.32, 95% CI:
      0.10-0.98). A three-fold increase in relative odds of speech disorder was found
      for finger-sucking behavior (OR: 2.99, 95% CI: 1.10-8.00) and for use of a
      pacifier for 3 or more years (OR: 3.42, 95% CI: 1.08-10.81). CONCLUSION: The
      results suggest extended use of sucking outside of breastfeeding may have
      detrimental effects on speech development in young children.

PMID- 19845937
TI  - Evaluation of an algorithm for estimating a patient's life threat risk from an
      ambulance call.
AB  - BACKGROUND: Utilizing a computer algorithm, information from calls to an
      ambulance service was used to calculate the risk of patients being in a life
      threatening condition (life threat risk), at the time of the call. If the
      estimated life threat risk was higher than 10%, the probability that a patient
      faced a risk of dying was recognized as very high and categorized as category A+.
      The present study aimed to review the accuracy of the algorithm. METHODS: Data
      collected for six months from the Yokohama new emergency system was used. In the
      system, emergency call workers interviewed ambulance callers to obtain
      information necessary to assess triage, which included consciousness level,
      breathing status, walking ability, position, and complexion. An emergency
      patient's life threat risk was then estimated by a computer algorithm applying
      logistic models. This study compared the estimated life threat risk occurring at
      the time of the emergency call to the patients' state or severity of condition,
      i.e. death confirmed at the scene by ambulance crews, resulted in death at
      emergency departments, life-threatening condition with occurrence of cardiac
      and/or pulmonary arrest (CPA), life-threatening condition without CPA, serious
      but not life-threatening condition, moderate condition, and mild condition. The
      sensitivity, specificity, predictive values, and likelihood ratios of the
      algorithm for categorizing A+ were calculated. RESULTS: The number of emergency
      dispatches over the six months was 73,992. Triage assessment was conducted for
      68,692 of these calls. The study targets account for 88.8% of patients who were
      involved in triage calls. There were 2,349 cases where the patient had died or
      had suffered CPA. The sensitivity, specificity, positive predictive value,
      negative predictive value, positive likelihood ratio and negative likelihood
      ratio of the algorithm at predicting cases that would result in a death or CPA
      were 80.2% (95% confidence interval: 78.6% - 81.8%), 96.0% (95.8% - 96.1%), 42.6%
      (41.1% - 44.0%), 99.2% (99.2% - 99.3%), 19.9 (18.8 - 21.1), and 0.21 (0.19 -
      0.22), respectively. CONCLUSION: A patient's life threat risk was quantitatively
      assessed at the moment of the emergency call with a moderate level of accuracy.

PMID- 19845938
TI  - Tissue doppler imaging can be useful to distinguish pathological from
      physiological left ventricular hypertrophy: a study in master athletes and mild
      hypertensive subjects.
AB  - BACKGROUND: Transthoracic echocardiography left ventricular wall thickness is
      often increased in master athletes and it results by intense physical training.
      Left Ventricular Hypertrophy can also be due to a constant pressure overload.
      Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes
      fails to distinguish physiological from pathological LVH.The aim of this study is
      to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating
      pathological from physiological LVH in the middle-aged population. METHODS: we
      selected a group of 80 master athletes, a group of 80 sedentary subjects with
      essential hypertension and an apparent normal diastolic function at standard PW
      Doppler analysis. The two groups were comparable for increased left ventricular
      wall thickness and mass index (134.4 +/- 19.7 vs 134.5 +/- 22.1 gr/m2; p > .05).
      Diastolic function indexes using the PW technique were in the normal range for
      both. RESULTS: Pulsed Wave TDI study of diastolic function immediately
      distinguished the two groups. While in master athletes the diastolic TDI-derived
      parameters remained within normal range (E' 9.4 +/- 3.1 cm/sec; E/E' 7.8 +/-
      2.1), in the hypertensive group these parameters were found to be constantly
      altered, with mean values and variation ranges always outside normal validated
      limits (E' 7.2 +/- 2.4 cm/sec; E/E' 10.6 +/- 3.2), and with E' and E/E'
      statistically different in the two groups (p < .001). CONCLUSION: Our study
      showed that the TDI technique can be an easy and validated method to assess
      diastolic function in differentiating normal from pseudonormal diastolic patterns
      and it can distinguish physiological from pathological LVH emphasizing the
      eligibility certification required by legal medical legislation as in Italy.

PMID- 19845939
TI  - Mitomycin C induces bystander killing in homogeneous and heterogeneous hepatoma
      cellular models.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers
      worldwide that is particularly refractory to chemotherapy. Several studies have
      proposed combination chemotherapy regimen for HCC treatment. However, these
      therapies are not effective in regressing tumor and prolonging survival of
      patient's suffering from HCC. Therefore, the development of more effective
      therapeutic tools and new strategies for the treatment of HCC are urgently
      needed. Over the last decade much attention has been focused on "bystander
      effect" as a possible therapeutic strategy for the treatment of certain human
      tumors. Interest in this therapeutic approach originated from numerous reports
      describing the radiation induced bystander effect. However, the knowledge about
      chemotherapy induced bystander effect is still limited. Hence, chemotherapy
      induced bystander phenomenon in hepatoma cells was explored by utilizing
      Mitomycin C (MMC). RESULTS: MMC induced bystander killing was observed only in
      hepatoma cells and it did not occur in cervical cancer cells. MMC induced
      bystander killing was transferable via medium. It occurred in co-cultured cells
      indicating the involvement of secreted as well as membrane bound factors. FasL
      and TRAIL were detected in the conditioned medium from treated cells. In medium
      transfer experiment, pre-treatment with EDTA (a broad range protease inhibitor)
      diminished MMC induced bystander killing. Following drug exposure, expression of
      Fas and TRAIL receptors increased and treatment with neutralizing antibodies
      against FasL and TRAIL inhibited bystander killing. CONCLUSION: Our results
      highlight the therapeutic importance of MMC in the treatment of HCC and implicate
      role of membrane bound and secreted forms of FasL and TRAIL in MMC induced
      bystander killing.

PMID- 19845940
TI  - Dietary composition modulates brain mass and solubilizable Abeta levels in a
      mouse model of aggressive Alzheimer's amyloid pathology.
AB  - OBJECTIVE: Alzheimer's disease (AD) is a progressive neurodegenerative disease of
      the central nervous system (CNS). Recently, an increased interest in the role
      diet plays in the pathology of AD has resulted in a focus on the detrimental
      effects of diets high in cholesterol and fat and the beneficial effects of
      caloric restriction. The current study examines how dietary composition modulates
      cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD.
      METHODS: From 4 wks until 18 wks of age, male and female TgCRND8 mice were
      maintained on one of four diets: (1) reference (regular) commercial chow; (2)
      high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal%
      carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30
      kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow
      (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were
      sacrificed, and brains studied for (a) wet weight; (b) solubilizable Abeta
      content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected
      hippocampal subregions. RESULTS: Animals receiving a high fat diet showed
      increased brain levels of solubilizable Abeta, although we detected no effect on
      plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate
      diet were 5% lower in weight than brains from all other mice. In an effort to
      identify regions that might link loss of brain mass to cognitive function, we
      studied neuronal density and volume in hippocampal subregions. Neuronal density
      and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in
      TgCRND8 mice receiving the high protein/low carbohydrate diet than in those
      receiving the regular chow. Neuronal density and volume were preserved in CA1 and
      in the dentate gyrus. INTERPRETATION: Dissociation of Abeta changes from brain
      mass changes raises the possibility that diet plays a role not only in modulating
      amyloidosis but also in modulating neuronal vulnerability. However, in the
      absence of a study of the effects of a high protein/low carbohydrate diet on
      nontransgenic mice, one cannot be certain how much, if any, of the loss of brain
      mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to
      an interaction between cerebral amyloidosis and diet. Given the recent evidence
      that certain factors favor the maintenance of cognitive function in the face of
      substantial structural neuropathology, we propose that there might also exist
      factors that sensitize brain neurons to some forms of neurotoxicity, including,
      perhaps, amyloid neurotoxicity. Identification of these factors could help
      reconcile the poor clinicopathological correlation between cognitive status and
      structural neuropathology, including amyloid pathology.

PMID- 19845941
TI  - Cytokeratin 8 ectoplasmic domain binds urokinase-type plasminogen activator to
      breast tumor cells and modulates their adhesion, growth and invasiveness.
AB  - BACKGROUND: Generation of plasmin is a characteristic of tumor cells, promoting
      the degradation of extracellular matrix, tumor progression and metastasis. The
      process is accelerated if plasminogen and plasminogen activator are bound to
      their cell surface receptors. RESULTS: In this study we show that the monoclonal
      antibody that recognizes an epitope on the cytokeratin 8 (CK8) ectoplasmic domain
      (anti-CK MAb) inhibits plasminogen activation mediated by urokinase-type
      plasminogen activator (uPA) in MCF-7 and MCF-10A neoT cells. The ectoplasmic
      domain of CK8 acts as a binding site for plasminogen, however, by using confocal
      microscopy, we demonstrated that it is also co-localized with uPA. CK8,
      therefore, function also as a receptor for uPA on the cell surface, and the
      presence of anti-CK MAb may prevent the binding of uPA to a designated CK8 motif.
      The consequent inhibition of plasmin generation resulted in changed cell
      morphology, enhanced cell adhesion to fibronectin, reduced invasion potential,
      and an enhanced G1/S transition. Moreover, surface plasmon resonance analysis
      showed that the synthetic dodecapeptide corresponding to the epitope sequence
      (VKIALEVEIATY), binds uPA in the nanomolar range. CONCLUSION: These novel
      findings suggest a model in which CK8, together with uPA, plasminogen and
      fibronectin, constitutes a signaling platform capable of modulating cell
      adhesion/growth-dependent signal transduction in breast tumor cells. Anti-CK MAb,
      which competes for the binding site for uPA, could be used as an agent to reduce
      the invasive potential of breast tumor cells.

PMID- 19845944
TI  - Retrospective analysis of 119 Chinese noninflammatory locally advanced breast
      cancer cases treated with intravenous combination of vinorelbine and epirubicin
      as a neoadjuvant chemotherapy: a median follow-up of 63.4 months.
AB  - BACKGROUND: This study is a retrospective evaluation of the efficacy of
      neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E)
      intravenous combination regimen and is aimed at identification of predictive
      markers for the long-term outcome in noninflammatory locally advanced breast
      cancer (NLABC). METHODS: One-hundred-and-nineteen patients with NLABC were
      identified from September 2001 to May 2006. Analysis was performed in March 2008,
      with a median follow-up of 63.4 months (range, 9-76 months). All patients were
      diagnosed with invasive breast cancer using 14 G core needle biopsy and treated
      with three cycles of VE before surgery. Local-regional radiotherapy was offered
      to all patients after the completion of chemotherapy followed by hormonal therapy
      according to hormone receptor status. Tissue sections cut from formalin-fixed
      paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues
      were stained for the presence of estrogen receptor (ER), progesterone receptor
      (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67).
      RESULTS: Patients characteristics were median age 52 years (range: 25-70 years);
      clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22)
      and stage IIIC (n = 9). All patients were evaluable for response: clinically
      complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained
      partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had
      progressive disease. Pathological complete response was found in 22 cases
      (18.5%). Seventy-five patients were alive with no recurrence after a median
      follow-up of 63.4 months, the 5-year rates for disease-free survival and overall
      survival were 58.7% and 71.3%, respectively, after the start of NC. On
      multivariate analysis, the independent variables associated with increased risk
      of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively),
      high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p =
      0.034, p = 0.027, respectively). A significantly increased risk of death was
      associated with lack of pre-ER expression (p = 0.002). Among patients with non
      pCR, those with a pathological response at the tumor site with special
      involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk
      of disease relapse and death (p < 0.001, p = 0.001, respectively). CONCLUSION:
      This study suggests the promising use of a VE regimen as NC for Chinese NLABC
      after a median follow-up of 63.4 months. Pathological response in the tumor site,
      pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important
      variables that predicted long-term outcome. Patients with pathological special
      involvement at the primary site after NC had the lowest survival rates.

PMID- 19845942
TI  - Distribution and determinants of patient satisfaction in oncology with a focus on
      health related quality of life.
AB  - BACKGROUND: Cancer patients usually undergo extensive and debilitating
      treatments, which make quality of life (QoL) and patient satisfaction important
      health care assessment measures. However, very few studies have evaluated the
      relationship between QoL and patient satisfaction in oncology. We investigated
      the clinical, demographic and QoL factors associated with patient satisfaction in
      a large heterogeneous sample of cancer patients. METHODS: A cohort of 538 cancer
      patients treated at Cancer Treatment Centers of America (CTCA) was assessed. A
      patient satisfaction questionnaire developed in-house by CTCA was used. It
      covered the following dimensions of patient satisfaction: hospital operations and
      services, physicians and staff, and patient endorsements for themselves and
      others. QoL was assessed using the European Organization for the Research and
      Treatment of Cancer Quality of Life Questionnaire (QLQ-C30). The clinical,
      demographic and QoL factors were evaluated for predictive significance using
      univariate and multivariate logistic regression. RESULTS: The mean age of our
      patient population was 54.1 years (SD = 10.5, range 17-86), with a slight
      preponderance of females (57.2%). Breast cancer (n = 124) and lung cancer (n =
      101) were the most frequent cancer types. 481 (89.4%) patients were "very
      satisfied" with their overall experience. Age and several QoL function and
      symptom scales were predictive of overall patient satisfaction upon univariate
      analysis. In the multivariate modeling, only those with a score above the median
      on the fatigue measure (i.e. worse fatigue) had reduced odds of 0.28 of being
      very satisfied (p = 0.03). CONCLUSION: Patient fatigue, as reported by the QoL
      fatigue scale, was an independent significant predictor of overall patient
      satisfaction. This finding argues for special attention and programs for cancer
      patients who report higher levels of fatigue given that fatigue is the most
      frequently reported symptom in cancer patients.

PMID- 19845945
TI  - Analysis of genomic signatures in prokaryotes using multinomial regression and
      hierarchical clustering.
AB  - BACKGROUND: Recently there has been an explosion in the availability of bacterial
      genomic sequences, making possible now an analysis of genomic signatures across
      more than 800 hundred different bacterial chromosomes, from a wide variety of
      environments.Using genomic signatures, we pair-wise compared 867 different
      genomic DNA sequences, taken from chromosomes and plasmids more than 100,000 base
      pairs in length. Hierarchical clustering was performed on the outcome of the
      comparisons before a multinomial regression model was fitted. The regression
      model included the cluster groups as the response variable with AT content,
      phyla, growth temperature, selective pressure, habitat, sequence size, oxygen
      requirement and pathogenicity as predictors. RESULTS: Many significant factors
      were associated with the genomic signature, most notably AT content. Phyla was
      also an important factor, although considerably less so than AT content. Small
      improvements to the regression model, although significant, were also obtained by
      factors such as sequence size, habitat, growth temperature, selective pressure
      measured as oligonucleotide usage variance, and oxygen requirement. CONCLUSION:
      The statistics obtained using hierarchical clustering and multinomial regression
      analysis indicate that the genomic signature is shaped by many factors, and this
      may explain the varying ability to classify prokaryotic organisms below genus
      level.

PMID- 19845946
TI  - A dosimetric comparison of four treatment planning methods for high grade glioma.
AB  - BACKGROUND: High grade gliomas (HGG) are typically treated with a combination of
      surgery, radiotherapy and chemotherapy. Three dimensional (3D) conformal
      radiotherapy treatment planning is still the main stay of treatment for these
      patients. New treatment planning methods suggest better dose distributions and
      organ sparing but their clinical benefit is unclear. The purpose of the current
      study was to compare normal tissue sparing and tumor coverage using four
      different radiotherapy planning methods in patients with high grade glioma.
      METHODS: Three dimensional conformal (3D), sequential boost IMRT, integrated
      boost (IB) IMRT and Tomotherapy (TOMO) treatment plans were generated for 20 high
      grade glioma patients. T1 and T2 MRI abnormalities were used to define GTV and
      CTV with 2 and 2.5 cm margins to define PTV1 and PTV2 respectively. RESULTS: The
      mean dose to PTV2 but not to PTV1 was less then 95% of the prescribed dose with
      IB and IMRT plans. The mean doses to the optic chiasm and the ipsilateral globe
      were highest with 3D plans and least with IB plans. The mean dose to the
      contralateral globe was highest with TOMO plans. The mean of the integral dose
      (ID) to the brain was least with the IB plan and was lower with IMRT compared to
      3D plans. The TOMO plans had the least mean D10 to the normal brain but higher
      mean D50 and D90 compared to IB and IMRT plans. The mean D10 and D50 but not D90
      were significantly lower with the IMRT plans compared to the 3D plans.
      CONCLUSION: No single treatment planning method was found to be superior to all
      others and a personalized approach is advised for planning and treating high
      grade glioma patients with radiotherapy. Integral dose did not reflect accurately
      the dose volume histogram (DVH) of the normal brain and may not be a good
      indicator of delayed radiation toxicity.

PMID- 19845947
TI  - Evaluation of psychological and physiological predictors of fatigue in patients
      with COPD.
AB  - BACKGROUND: Fatigue in COPD impairs functional status; however there are few
      studies examining mechanistic pathways of this symptom. The aims of this study
      are to compare fatigue between COPD patients and healthy age-matched subjects,
      and to identify predictors of fatigue in COPD. METHODS: Seventy four COPD
      patients, mean age 69.9 (49-87) yrs, mean (SD) % predicted FEV1 46.5 (20.0) % and
      FEV1/FVC ratio 0.45 (0.13) and 35 healthy subjects, mean age 67.1 (50-84) yrs
      completed the Multidimensional Fatigue Inventory (MFI 20). Patients' assessment
      included Depression (HADS), lung function, BMI, muscle strength, incremental
      shuttle walk test (ISWT), exercise oxygen saturation (SpO2), Borg breathlessness
      (CR-10) and exertion (RPE). Serum level of Interleukin 6 (IL-6) was recorded.
      Differences in MFI 20 between groups were examined and predictors of fatigue
      identified using logistic regression. RESULTS: Significant differences (p < 0.01)
      were found between the COPD and healthy subjects for all MFI 20 dimensions. There
      were significant differences when classified according to GOLD and dyspnoea
      stages for selected dimensions only. Predictors of General Fatigue were
      depression, muscle strength and end SpO2 (R2 = .62); of Physical Fatigue:
      depression, % predicted FEV1, ISWT and age (R2 = .57); Reduced Activity: %
      predicted FEV1, BMI and depression (R2 = .36); Reduced Motivation: RPE,
      depression and end SpO2 (R2 = .37) and Mental Fatigue: depression and end SpO2
      (R2 = .38). CONCLUSION: All dimensions of fatigue were higher in COPD than
      healthy aged subjects. Predictive factors differ according to the dimension of
      fatigue under investigation. COPD-RF is a multi component symptom requiring
      further consideration.

PMID- 19845948
TI  - "It depends on what you mean": a qualitative study of Swedish health
      professionals' views on health and health promotion.
AB  - BACKGROUND: The role of health services must be re-oriented towards health
      promotion to more effectively contribute to population health. One of the
      objectives of the Swedish public health policy is that health promotion and
      disease prevention should be an integral part of the health care system and an
      important component of all care and treatment. However, the uncertainty about
      what the concepts of health and health promotion mean poses a challenge for
      implementation. Depending on how these concepts are interpreted, the attitudes of
      health professionals toward health promoting practices will differ. Thus, a more
      in-depth understanding of health professionals' views can be a starting point for
      a discussion about the values and attitudes that influence the current health
      care system and about the barriers and possibilities for future development of a
      health promoting health service. METHODS: Seven focus group discussions (n = 34)
      were carried out with health professionals, from different health care settings,
      to understand how they communicate about health and health promotion. The data
      were analyzed using qualitative content analysis. RESULTS: The analysis of health
      professional's general understanding of the concept of health resulted in the
      category; a multi-facetted concept, whilst the category; a subjective assessment
      describes what health means to themselves. A third category; health is about
      life, the whole life. describes their understanding of health as an outcome of a
      multiplicity of contextually dependent determinants. The health professional's
      multiple ways of associating health promotion to disease prevention suggest a
      concept that is diffuse, elusive and difficult to apply in practice. Despite a
      shared view of health, the health professionals described their health promotion
      role very differently depending partly on how the concept of health promotion was
      interpreted. The analysis resulted in the development of three ideal types,
      labelled the demarcater, the integrater and the promoter describing different
      strategies for handling a health promotion role in practice CONCLUSION: The study
      suggests that different interpretations of what constitutes health promotion can
      lead to unnecessary misunderstandings and pose barriers to further development of
      a health promoting practice.

PMID- 19845949
TI  - Increased cardiac index due to terbutaline treatment aggravates capillary
      alveolar macromolecular leakage in oleic acid lung injury in dogs.
AB  - INTRODUCTION: We assessed the in vivo effects of terbutaline, a beta2-agonist
      assumed to reduce microvascular permeability in acute lung injury. METHODS: We
      used a recently developed broncho-alveolar lavage (BAL) technique to repeatedly
      measure (every 15 min. for 4 hours) the time-course of capillary-alveolar leakage
      of a macromolecule (fluorescein-labeled dextran) in 19 oleic acid (OA) lung
      injured dogs. BAL was performed in a closed lung sampling site, using a
      bronchoscope fitted with an inflatable cuff. Fluorescein-labeled Dextran (FITC
      D70) was continuously infused and its concentration measured in plasma and BAL
      fluid. A two-compartment model (blood and alveoli) was used to calculate KAB, the
      transport rate coefficient of FITC-D70 from blood to alveoli. KAB was estimated
      every 15 minutes over 4 hours. Terbutaline intra-venous perfusion was started 90
      min. after the onset of the injury and then continuously infused until the end of
      the experiment. RESULTS: In the non-treated injured group, the capillary-alveolar
      leakage of FITC-D70 reached a peak within 30 minutes after the OA injury.
      Thereafter the FITC-D70 leakage decreased gradually until the end of the
      experiment. Terbutaline infusion, started 90 min after injury, interrupted the
      recovery with an aggravation in FITC-D70 leakage. CONCLUSIONS: As cardiac index
      increased with terbutaline infusion, we speculate that terbutaline recruits leaky
      capillaries and increases FITC-D70 leakage after OA injury. These findings
      suggest that therapies inducing an increase in cardiac output and a decrease in
      pulmonary vascular resistances have the potential to heighten the early increase
      in protein transport from plasma to alveoli within the acutely injured lung.

PMID- 19845950
TI  - Persistent treatment with cholinesterase inhibitors and/or memantine slows
      clinical progression of Alzheimer disease.
AB  - INTRODUCTION: There are no empiric data to support guidelines for duration of
      therapy with antidementia drugs. This study examined whether persistent use of
      antidementia drugs slows clinical progression of Alzheimer disease (AD) assessed
      by repeated measures on serial tests of cognition and function. METHODS: Six
      hundred forty-one probable AD patients were followed prospectively at an academic
      center over 20 years. Cumulative drug exposure was expressed as a persistency
      index (PI) reflecting total years of drug use divided by total years of disease
      symptoms. Baseline and annual testing consisted of Mini-Mental State Examination
      (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog),
      Baylor Profound Mental Status Examination (BPMSE), Clinical Dementia Rating-Sum
      of Boxes (CDR-SB), Physical Self-Maintenance Scale (PSMS), and Instrumental
      Activities of Daily Living (IADL). Annual change in slope of neuropsychological
      and functional tests as predicted by follow-up time, PI, and the interaction of
      these two variables was evaluated. RESULTS: PI was associated with significantly
      slower rates of decline (with, without adjustment for covariates) on MMSE (P <
      0.0001), PSMS (P < 0.05), IADL (P < 0.0001), and CDR-SB (P < 0.001). There was an
      insignificant trend (P = 0.053) for the PI to be associated with slower rate of
      decline on BPMSE. The association of PI with ADAS-Cog followed a quadratic trend
      (P < 0.01). Analysis including both linear and quadratic terms suggests that PI
      slowed ADAS-Cog decline temporarily. The magnitude of the favorable effect of a
      rate change in PI was: MMSE 1 point per year, PSMS 0.4 points per year, IADL 1.4
      points per year, and CDR-SB 0.6 points per year. The change in mean test scores
      is additive over the follow-up period (3 +/- 1.94 years). CONCLUSIONS: Persistent
      drug treatment had a positive impact on AD progression assessed by multiple
      cognitive, functional, and global outcome measures. The magnitude of the
      treatment effect was clinically significant. Positive treatment effects were even
      found in those with advanced disease.

PMID- 19845951
TI  - Impact of 4.0% chlorhexidine cleansing of the umbilical cord on mortality and
      omphalitis among newborns of Sylhet, Bangladesh: design of a community-based
      cluster randomized trial.
AB  - BACKGROUND: The World Health Organization recommends dry cord care for newborns
      but this recommendation may not be optimal in low resource settings where most
      births take place in an unclean environment and infections account for up to half
      of neonatal deaths. A previous trial in Nepal indicated that umbilical cord
      cleansing with 4.0% chlorhexidine could substantially reduce mortality and
      omphalitis risk, but policy changes await additional community-based data.
      METHODS: The Projahnmo Chlorhexidine study was a three-year, cluster-randomized,
      community-based trial to assess the impact of three cord care regimens on
      neonatal mortality and omphalitis. Women were recruited mid-pregnancy, received a
      basic package of maternal and neonatal health promotion messages, and were
      followed to pregnancy outcome. Newborns were visited at home by local village
      based workers whose areas were randomized to either 1) single- or 2) 7-day cord
      cleansing with 4.0% chlorhexidine, or 3) promotion of dry cord care as
      recommended by WHO. All mothers received basic messages regarding hand-washing,
      clean cord cutting, and avoidance of harmful home-base applications to the cord.
      Death within 28 days and omphalitis were the primary outcomes; these were
      monitored directly through home visits by community health workers on days 1, 3,
      6, 9, 15, and 28 after birth. DISCUSSION: Due to report in early 2010, the
      Projahnmo Chlorhexidine Study examines the impact of multiple or single
      chlorhexidine cleansing of the cord on neonatal mortality and omphalitis among
      newborns of rural Sylhet District, Bangladesh. The results of this trial will be
      interpreted in conjunction with a similarly designed trial previously conducted
      in Nepal, and will have implications for policy guidelines for optimal cord care
      of newborns in low resource settings in Asia. TRIAL REGISTRATION:
      ClinicalTrials.gov (NCT00434408).

PMID- 19845952
TI  - HLA-Cw*04 allele associated with nevirapine-induced rash in HIV-infected Thai
      patients.
AB  - BACKGROUND: A high incidence of rash has been reported in HIV-1 patients who
      received the anti-retroviral drug nevirapine. In addition, several studies have
      suggested that polymorphisms of human leukocyte antigen (HLA) genes may play
      important roles in nevirapine-induced rash. The aim of the present study was to
      evaluate the effects of different HLA-C alleles on rash associated with
      nevirapine in patients who started highly active anti-retroviral therapy (HAART)
      containing nevirapine in Thailand. RESULTS: A case-control study was carried out
      involving HIV-1 patients under treatment at Bamrasnaradura Infectious Diseases
      Institute, Nonthaburi, Thailand between March 2007 and March 2008. The study
      included all HIV/AIDS patients being treated with nevirapine-containing regimens.
      The study population comprised 287 HIV/AIDS patients of whom 248 were nevirapine
      tolerant and 39 developed rash after nevirapine treatment. From the nevirapine
      tolerant patients, 60 were selected as the control group on the basis of age,
      sex, and therapy history matched for nevirapine-induced rash cases. We observed
      significantly more HLA-Cw*04 alleles in nevirapine-induced rash cases than in
      nevirapine-tolerant group, with frequencies of 20.51% and 7.50%, respectively (P
      = 0.009). There were no significant differences between the rash and tolerant
      groups for other HLA-C alleles except for HLA-Cw*03 (P = 0.015). CONCLUSION: This
      study suggests that HLA-Cw*04 is associated with rash in nevirapine treated
      Thais. Future screening of patients' HLA may reduce the number of nevirapine
      induced rash cases, and patients with alleles associated with nevirapine-induced
      rash should be started on anti-retroviral therapy without nevirapine.

PMID- 19845953
TI  - Arabidopsis gene co-expression network and its functional modules.
AB  - BACKGROUND: Biological networks characterize the interactions of biomolecules at
      a systems-level. One important property of biological networks is the modular
      structure, in which nodes are densely connected with each other, but between
      which there are only sparse connections. In this report, we attempted to find the
      relationship between the network topology and formation of modular structure by
      comparing gene co-expression networks with random networks. The organization of
      gene functional modules was also investigated. RESULTS: We constructed a genome
      wide Arabidopsis gene co-expression network (AGCN) by using 1094 microarrays. We
      then analyzed the topological properties of AGCN and partitioned the network into
      modules by using an efficient graph clustering algorithm. In the AGCN, 382 hub
      genes formed a clique, and they were densely connected only to a small subset of
      the network. At the module level, the network clustering results provide a
      systems-level understanding of the gene modules that coordinate multiple
      biological processes to carry out specific biological functions. For instance,
      the photosynthesis module in AGCN involves a very large number (> 1000) of genes
      which participate in various biological processes including photosynthesis,
      electron transport, pigment metabolism, chloroplast organization and biogenesis,
      cofactor metabolism, protein biosynthesis, and vitamin metabolism. The cell cycle
      module orchestrated the coordinated expression of hundreds of genes involved in
      cell cycle, DNA metabolism, and cytoskeleton organization and biogenesis. We also
      compared the AGCN constructed in this study with a graphical Gaussian model (GGM)
      based Arabidopsis gene network. The photosynthesis, protein biosynthesis, and
      cell cycle modules identified from the GGM network had much smaller module sizes
      compared with the modules found in the AGCN, respectively. CONCLUSION: This study
      reveals new insight into the topological properties of biological networks. The
      preferential hub-hub connections might be necessary for the formation of modular
      structure in gene co-expression networks. The study also reveals new insight into
      the organization of gene functional modules.

PMID- 19845954
TI  - Analysis of regulatory protease sequences identified through bioinformatic data
      mining of the Schistosoma mansoni genome.
AB  - BACKGROUND: New chemotherapeutic agents against Schistosoma mansoni, an
      etiological agent of human schistosomiasis, are a priority due to the emerging
      drug resistance and the inability of current drug treatments to prevent
      reinfection. Proteases have been under scrutiny as targets of immunological or
      chemotherapeutic anti-Schistosoma agents because of their vital role in many
      stages of the parasitic life cycle. Function has been established for only a
      handful of identified S. mansoni proteases, and the vast majority of these are
      the digestive proteases; very few of the conserved classes of regulatory
      proteases have been identified from Schistosoma species, despite their vital role
      in numerous cellular processes. To that end, we identified protease protein
      coding genes from the S. mansoni genome project and EST library. RESULTS: We
      identified 255 protease sequences from five catalytic classes using predicted
      proteins of the S. mansoni genome. The vast majority of these show significant
      similarity to proteins in KEGG and the Conserved Domain Database. Proteases
      include calpains, caspases, cytosolic and mitochondrial signal peptidases,
      proteases that interact with ubiquitin and ubiquitin-like molecules, and
      proteases that perform regulated intramembrane proteolysis. Comparative analysis
      of classes of important regulatory proteases find conserved active site domains,
      and where appropriate, signal peptides and transmembrane helices. Phylogenetic
      analysis provides support for inferring functional divergence among regulatory
      aspartic, cysteine, and serine proteases. CONCLUSION: Numerous proteases are
      identified for the first time in S. mansoni. We characterized important
      regulatory proteases and focus analysis on these proteases to complement the
      growing knowledge base of digestive proteases. This work provides a foundation
      for expanding knowledge of proteases in Schistosoma species and examining their
      diverse function and potential as targets for new chemotherapies.

PMID- 19845955
TI  - Aberrant STYK1 expression in ovarian cancer tissues and cell lines.
AB  - BACKGROUND: Overexpression of STYK1, a putative serine/threonine and tyrosine
      receptor protein kinase has been shown to confer tumorigenicity and metastatic
      potential to normal cells injected into nude mice. Mutation of a tyrosine residue
      in the catalytic STYK1 domain attenuates the tumorigenic potential of tumor cells
      in vivo, collectively, suggesting an oncogenic role for STYK1. METHODS: To
      investigate the role of STYK1 expression in ovarian cancer, a panel of normal,
      benign, and ovarian cancer tissues was evaluated for STYK1 immunoreactivity using
      STYK1 antibodies. In addition, mRNA levels were measured by reverse transcription
      PCR and real-time PCR of estrogen receptors, GPR30 and STYK1 following treatment
      of ovarian cell lines with estrogen or G1, a GPR30 agonist, as well as western
      analysis. RESULTS: Our data showed higher expression of STYK1 in cancer tissues
      versus normal or benign. Only normal or benign, and one cancer tissue were STYK1
      negative. Moreover, benign and ovarian cancer cell lines expressed STYK1 as
      determined by RT-PCR. Estradiol treatment of these cells resulted in up- and down
      regulation of STYK1 despite estrogen receptor status; whereas G-1, a GPR30
      specific agonist, increased STYK1 mRNA levels higher than that of estradiol.
      CONCLUSION: We conclude that STYK1 is expressed in ovarian cancer and is
      regulated by estrogen through a GPR30 hormone-signaling pathway, to the exclusion
      of estrogen receptor-alpha.

PMID- 19845956
TI  - One year mortality of patients treated with an emergency department based early
      goal directed therapy protocol for severe sepsis and septic shock: a before and
      after study.
AB  - INTRODUCTION: Early structured resuscitation of severe sepsis has been suggested
      to improve short term mortality; however, no previous study has examined the long
      term effect of this therapy. We sought to determine one year outcomes associated
      with implementation of early goal directed therapy (EGDT) in the emergency
      department (ED) care of sepsis. METHODS: We performed a longitudinal analysis of
      a prospective before and after study conducted at a large urban ED. Adult
      patients were enrolled if they had suspected infection, 2 or more systemic
      inflammatory response criteria, and either systolic blood pressure (SBP) <90 mmHg
      after a fluid bolus or lactate >4 mM. Exclusion criteria were: age <18 years, no
      aggressive care desired, or need for immediate surgery. Clinical and outcomes
      data were prospectively collected on consecutive eligible patients for 1 year
      before and 2 years after implementing EGDT. Patients in the pre-implementation
      phase received non-protocolized care at attending physician discretion. The
      primary outcome was mortality at one year. RESULTS: 285 subjects, 79 in the pre-
      and 206 in the post-implementation phases, were enrolled. Compared to pre
      implementation, post-implementation subjects had a significantly lower ED SBP (72
      vs. 85 mm Hg, P < 0.001) and higher sequential organ failure assessment score (7
      vs. 5, P = 0.0004). The primary outcome of 1 year mortality was observed in 39/79
      (49%) pre-implementation subjects and 77/206 (37%) post-implementation subjects
      (difference 12%; P = 0.04). CONCLUSIONS: Implementation of EGDT for the treatment
      of ED patients with severe sepsis and septic shock was associated with
      significantly lower mortality at one year.

PMID- 19845957
TI  - Dual effect of a single nucleotide polymorphism in the first intron of the
      porcine secreted phosphoprotein 1 gene: allele-specific binding of C/EBP beta and
      activation of aberrant splicing.
AB  - BACKGROUND: Secreted phosphoprotein 1 (SPP1 or Osteopontin, OPN) is a
      multifunctional matricellular glycoprotein involved in development and
      regeneration of skeletal muscle. Previously, we have demonstrated that porcine
      SPP1 shows breed-related differential mRNA expression during myogenesis. With the
      aim to identify putative contributing cis-regulatory DNA variation we resequenced
      the 5' upstream region of the gene in the respective breeds Pietrain and Duroc.
      We found two single nucleotide polymorphisms (SNP; [GenBank:M84121]: g.1804C>T
      and g.3836A>G). We focused our investigation on the SNP g.3836A>G, because in
      silico analysis and knowledge about the regulation of SPP1 suggested an effect of
      this SNP on a CCAAT/enhancer binding protein beta (C/EBPbeta) responsive
      transcriptional enhancer. RESULTS: Using electrophoretic mobility shift assay we
      demonstrated that, similar to human SPP1, the 3' terminal end of the first intron
      of porcine SPP1 harbors a C/EBPbeta binding site and showed that this binding
      site is negatively affected by the mutant G allele. Genotyping of 48 fetuses per
      breed revealed that the G allele segregated exclusively in Duroc fetuses with a
      frequency of 57 percent. Using real-time quantitative PCR we showed that,
      consistent with its negative effect on a transcriptional enhancer element, the G
      allele tends to decrease mRNA abundance of SPP1 in the fetal musculus longissimus
      dorsi (approximately 1.3 fold; P > or = 0.1). Moreover, we showed that the SNP
      g.3836A>G leads to ubiquitous aberrant splicing of the first intron by generating
      a de novo and activating a cryptic splice acceptor site. Aberrantly spliced
      transcripts comprise about half of the SPP1 messages expressed by the G allele.
      Both aberrant splice variants differ from the native transcript by insertions in
      the leader sequences which do not change the reading frame of SPP1. CONCLUSION:
      At the 3' terminal end of the first intron of the porcine SPP1 we identified a
      unique, dually functional SNP g.3836A>G. This SNP affects the function of the
      SPP1 gene at the DNA level by affecting a C/EBPbeta binding site and at the RNA
      level by activating aberrant splicing of the first intron, and thus represents an
      interesting DNA-marker to study phenotypic effects of SPP1 DNA-variation.

PMID- 19845958
TI  - Associations between dietary habits and body mass index with gut microbiota
      composition and fecal water genotoxicity: an observational study in African
      American and Caucasian American volunteers.
AB  - BACKGROUND: African Americans (AA) suffer from an increased incidence and
      mortality of colorectal cancer (CRC). Environmental exposures including dietary
      habits likely contribute to a high burden of CRC, however, data on the dietary
      habits of AA is sparse. Diet might change the composition and the activities of
      the intestinal microbiota, in turn affecting fecal genotoxicity/mutagenicity that
      is thought to be associated with carcinogenesis. METHODS: We assessed dietary
      habits by food frequency questionnaire and by food records in 52 AA and 46 CA
      residents of the Eastern Shore of MD. Fecal microbiota composition was determined
      using 16S rRNA based methods and fecal genotoxicity measured using the Comet
      assay. RESULTS: AA reported an increased intake of heterocyclic amines and a
      decreased dietary intake of vitamins including vitamin D (p<0.05) that correlated
      with differences in fecal microbiota composition but not fecal genotoxicity.
      Intake of dietary fiber, calcium, total fat and heterocyclic amines correlated
      with differences in microbiota composition. Total bacterial counts/g of stool and
      raw counts of Bacteroides were increased in AA. In contrast to a previous study,
      BMI was not associated with proportions of Bacteroides. CONCLUSION: Dietary
      habits of African Americans, including increased HCA intake and decreased vitamin
      D intake might at least partially contribute to CRC through modifications of gut
      microbiota composition that result in changes of the intestinal milieu.

PMID- 19845959
TI  - Novel immortalized human fetal liver cell line, cBAL111, has the potential to
      differentiate into functional hepatocytes.
AB  - BACKGROUND: A clonal cell line that combines both stable hepatic function and
      proliferation capacity is desirable for in vitro applications that depend on
      hepatic function, such as pharmacological or toxicological assays and
      bioartificial liver systems. Here we describe the generation and characterization
      of a clonal human cell line for in vitro hepatocyte applications. RESULTS: Cell
      clones derived from human fetal liver cells were immortalized by over-expression
      of telomerase reverse transcriptase. The resulting cell line, cBAL111, displayed
      hepatic functionality similar to the parental cells prior to immortalization, and
      did not grow in soft agar. Cell line cBAL111 expressed markers of immature
      hepatocytes, like glutathione S transferase and cytokeratin 19, as well as
      progenitor cell marker CD146 and was negative for lidocaine elimination. On the
      other hand, the cBAL111 cells produced urea, albumin and cytokeratin 18 and
      eliminated galactose. In contrast to hepatic cell lines NKNT-3 and HepG2, all
      hepatic functions were expressed in cBAL111, although there was considerable
      variation in their levels compared with primary mature hepatocytes. When
      transplanted in the spleen of immunodeficient mice, cBAL111 engrafted into the
      liver and partly differentiated into hepatocytes showing expression of human
      albumin and carbamoylphosphate synthetase without signs of cell fusion.
      CONCLUSION: This novel liver cell line has the potential to differentiate into
      mature hepatocytes to be used for in vitro hepatocyte applications.

PMID- 19845960
TI  - ParaHaplo: A program package for haplotype-based whole-genome association study
      using parallel computing.
AB  - BACKGROUND: Since more than a million single-nucleotide polymorphisms (SNPs) are
      analyzed in any given genome-wide association study (GWAS), performing multiple
      comparisons can be problematic. To cope with multiple-comparison problems in
      GWAS, haplotype-based algorithms were developed to correct for multiple
      comparisons at multiple SNP loci in linkage disequilibrium. A permutation test
      can also control problems inherent in multiple testing; however, both the
      calculation of exact probability and the execution of permutation tests are time
      consuming. Faster methods for calculating exact probabilities and executing
      permutation tests are required. METHODS: We developed a set of computer programs
      for the parallel computation of accurate P-values in haplotype-based GWAS. Our
      program, ParaHaplo, is intended for workstation clusters using the Intel Message
      Passing Interface (MPI). We compared the performance of our algorithm to that of
      the regular permutation test on JPT and CHB of HapMap. RESULTS: ParaHaplo can
      detect smaller differences between 2 populations than SNP-based GWAS. We also
      found that parallel-computing techniques made ParaHaplo 100-fold faster than a
      non-parallel version of the program. CONCLUSION: ParaHaplo is a useful tool in
      conducting haplotype-based GWAS. Since the data sizes of such projects continue
      to increase, the use of fast computations with parallel computing--such as that
      used in ParaHaplo--will become increasingly important. The executable binaries
      and program sources of ParaHaplo are available at the following address:
      http://sourceforge.jp/projects/parallelgwas/?_sl=1.

PMID- 19845961
TI  - Inter-rater reliability of the Foot Posture Index (FPI-6) in the assessment of
      the paediatric foot.
AB  - BACKGROUND: Reliability is an integral component of clinical assessment and
      necessary for establishing baseline data, monitoring treatment outcomes and
      providing robust research findings. In the podiatric literature traditional
      measures of foot assessment have been shown to be largely unreliable. The Foot
      Posture Index (FPI-6) is a clinical tool used in the assessment of foot and to
      date, there is limited research published which evaluates the reliability of this
      tool in children and adolescents. METHOD: Thirty participants aged 5 - 16 years
      were recruited for the research. Two raters independently recorded the FPI-6
      score for each participant. RESULTS: Almost perfect agreement between the two
      raters was identified following weighted kappa analysis (Kw = 0.86). CONCLUSION:
      The FPI-6 is a quick, simple and reliable clinical tool which has demonstrated
      excellent inter-rater reliability when used in the assessment of the paediatric
      foot.

PMID- 19845962
TI  - The impact of transportation infrastructure on bicycling injuries and crashes: a
      review of the literature.
AB  - BACKGROUND: Bicycling has the potential to improve fitness, diminish obesity, and
      reduce noise, air pollution, and greenhouse gases associated with travel.
      However, bicyclists incur a higher risk of injuries requiring hospitalization
      than motor vehicle occupants. Therefore, understanding ways of making bicycling
      safer and increasing rates of bicycling are important to improving population
      health. There is a growing body of research examining transportation
      infrastructure and the risk of injury to bicyclists. METHODS: We reviewed studies
      of the impact of transportation infrastructure on bicyclist safety. The results
      were tabulated within two categories of infrastructure, namely that at
      intersections (e.g. roundabouts, traffic lights) or between intersections on
      "straightaways" (e.g. bike lanes or paths). To assess safety, studies examining
      the following outcomes were included: injuries; injury severity; and crashes
      (collisions and/or falls). RESULTS: The literature to date on transportation
      infrastructure and cyclist safety is limited by the incomplete range of
      facilities studied and difficulties in controlling for exposure to risk. However,
      evidence from the 23 papers reviewed (eight that examined intersections and 15
      that examined straightaways) suggests that infrastructure influences injury and
      crash risk. Intersection studies focused mainly on roundabouts. They found that
      multi-lane roundabouts can significantly increase risk to bicyclists unless a
      separated cycle track is included in the design. Studies of straightaways grouped
      facilities into few categories, such that facilities with potentially different
      risks may have been classified within a single category. Results to date suggest
      that sidewalks and multi-use trails pose the highest risk, major roads are more
      hazardous than minor roads, and the presence of bicycle facilities (e.g. on-road
      bike routes, on-road marked bike lanes, and off-road bike paths) was associated
      with the lowest risk. CONCLUSION: Evidence is beginning to accumulate that
      purpose-built bicycle-specific facilities reduce crashes and injuries among
      cyclists, providing the basis for initial transportation engineering guidelines
      for cyclist safety. Street lighting, paved surfaces, and low-angled grades are
      additional factors that appear to improve cyclist safety. Future research
      examining a greater variety of infrastructure would allow development of more
      detailed guidelines.

PMID- 19845963
TI  - Potential impact of task-shifting on costs of antiretroviral therapy and
      physician supply in Uganda.
AB  - BACKGROUND: Lower-income countries face severe health worker shortages. Recent
      evidence suggests that this problem can be mitigated by task-shifting--delegation
      of aspects of health care to less specialized health workers. We estimated the
      potential impact of task-shifting on costs of antiretroviral therapy (ART) and
      physician supply in Uganda. The study was performed at the Infectious Diseases
      Institute (IDI) clinic, a large urban HIV clinic. METHODS: We built an aggregate
      cost-minimization model from societal and Ministry of Health (MOH) perspectives.
      We compared physician-intensive follow-up (PF), the standard of care, with two
      methods of task-shifting: nurse-intensive follow-up (NF) and pharmacy-worker
      intensive follow-up (PWF). We estimated personnel and patient time use using a
      time-motion survey. We obtained unit costs from IDI and the literature. We
      estimated physician personnel impact by calculating full time equivalent (FTE)
      physicians saved. We made national projections for Uganda. RESULTS: Annual mean
      costs of follow-up per patient were $59.88 (societal) and $31.68 (medical) for
      PF, $44.58 (societal) and $24.58 (medical) for NF and $18.66 (societal) and $10.5
      (medical) for PWF. Annual national societal ART follow-up expenditure was $5.92
      million using PF, $4.41 million using NF and $1.85 million using PWF, potentially
      saving $1.51 million annually by using NF and $4.07 million annually by using PWF
      instead of PF. Annual national MOH expenditure was $3.14 million for PF, $2.43
      million for NF and $1.04 for PWF, potentially saving $0.70 million by using NF
      and $2.10 million by using PWF instead of PF. Projected national physician
      personnel needs were 108 FTE doctors to implement PF and 18 FTE doctors to
      implement NF or PWF. Task-shifting from PF to NF or PWF would potentially save 90
      FTE physicians, 4.1% of the national physician workforce or 0.3 FTE physicians
      per 100,000 population. CONCLUSION: Task-shifting results in substantial cost and
      physician personnel savings in ART follow-up in Uganda and can contribute to
      mitigating the heath worker crisis.

PMID- 19845964
TI  - Chondroitin sulfate proteoglycans regulate the growth, differentiation and
      migration of multipotent neural precursor cells through the integrin signaling
      pathway.
AB  - BACKGROUND: Neural precursor cells (NPCs) are defined by their ability to
      proliferate, self-renew, and retain the potential to differentiate into neurons
      and glia. Deciphering the factors that regulate their behaviors will greatly aid
      in their use as potential therapeutic agents or targets. Chondroitin sulfate
      proteoglycans (CSPGs) are prominent components of the extracellular matrix (ECM)
      in the central nervous system (CNS) and are assumed to play important roles in
      controlling neuronal differentiation and development. RESULTS: In the present
      study, we demonstrated that CSPGs were constitutively expressed on the NPCs
      isolated from the E16 rat embryonic brain. When chondroitinase ABC was used to
      abolish the function of endogenous CSPGs on NPCs, it induced a series of
      biological responses including the proliferation, differentiation and migration
      of NPCs, indicating that CSPGs may play a critical role in NPC development and
      differentiation. Finally, we provided evidence suggesting that integrin signaling
      pathway may be involved in the effects of CSPGs on NPCs. CONCLUSION: The present
      study investigating the influence and mechanisms of CSPGs on the differentiation
      and migration of NPCs should help us to understand the basic biology of NPCs
      during CNS development and provide new insights into developing new strategies
      for the treatment of the neurological disorders in the CNS.

PMID- 19845965
TI  - Better mental health in children of Vietnamese refugees compared with their
      Norwegian peers--a matter of cultural difference?
AB  - BACKGROUND: There are conflicting results on whether immigrant children are at a
      heightened risk of mental health problems compared with native youth in the
      resettlement country. THE OBJECTIVE OF THE STUDY: To compare the mental health of
      94 Norwegian-born children from a community cohort of Vietnamese refugees, aged 4
      - 18 years, with that of a Norwegian community sample. METHODS: The SDQ was
      completed by two types of informants; the children's self-reports, and the
      parents' reports, for comparison with Norwegian data from the Health Profiles for
      Children and Youth in the Akershus study. RESULTS: The self-perceived mental
      health of second-generation Vietnamese in Norway was better than that of their
      Norwegian compatriots, as assessed by the SDQ. In the Norwegian-Vietnamese group,
      both children and parents reported a higher level of functioning. CONCLUSION:
      This surprising finding may result from the lower prevalence of mental distress
      in Norwegian-Vietnamese children compared with their Norwegian peers, or from
      biased reports and cultural differences in reporting emotional and behavioural
      problems. These findings may represent the positive results of the children's bi
      cultural competencies.

PMID- 19845966
TI  - Estimating average inpatient and outpatient costs and childhood pneumonia and
      diarrhoea treatment costs in an urban health centre in Zambia.
AB  - BACKGROUND: Millions of children die every year in developing countries, from
      preventable diseases such as pneumonia and diarrhoea, owing to low levels of
      investment in child health. Investment efforts are hampered by a general lack of
      adequate information that is necessary for priority setting in this sector. This
      paper measures the health system costs of providing inpatient and outpatient
      services, and also the costs associated with treating pneumonia and diarrhoea in
      under-five children at a health centre in Zambia. METHODS: Annual economic and
      financial cost data were collected in 2005-2006. Data were summarized in a
      Microsoft excel spreadsheet to obtain total department costs and average disease
      treatment costs. RESULTS: The total annual cost of operating the health centre
      was US$1,731,661 of which US$1 284 306 and US$447,355 were patient care and
      overhead departments costs, respectively. The average cost of providing out
      patient services was US$3 per visit, while the cost of in-patient treatment was
      US$18 per bed day. The cost of providing dental services was highest at US$20 per
      visit, and the cost of VCT services was lowest, with US$1 per visit. The cost per
      out-patient visit for under-five pneumonia was US$48, while the cost per bed day
      was US$215. The cost per outpatient visit attributed to under-five diarrhoea was
      US$26, and the cost per bed day was US$78. CONCLUSION: In the face of
      insufficient data, a cost analysis exercise is a difficult but feasible
      undertaking. The study findings are useful and applicable in similar settings,
      and can be used in cost effectiveness analyses of health interventions.

PMID- 19845967
TI  - Novel association of APC with intermediate filaments identified using a new
      versatile APC antibody.
AB  - BACKGROUND: As a key player in suppression of colon tumorigenesis, Adenomatous
      Polyposis Coli (APC) has been widely studied to determine its cellular functions.
      However, inconsistencies of commercially available APC antibodies have limited
      the exploration of APC function. APC is implicated in spindle formation by direct
      interactions with tubulin and microtubule-binding protein EB1. APC also interacts
      with the actin cytoskeleton to regulate cell polarity. Until now, interaction of
      APC with the third cytoskeletal element, intermediate filaments, has remained
      unexamined. RESULTS: We generated an APC antibody (APC-M2 pAb) raised against the
      15 amino acid repeat region, and verified its reliability in applications
      including immunoprecipitation, immunoblotting, and immunofluorescence in cultured
      cells and tissue. Utilizing this APC-M2 pAb, we immunoprecipitated endogenous APC
      and its binding proteins from colon epithelial cells expressing wild-type APC.
      Using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), we identified 42
      proteins in complex with APC, including beta-catenin and intermediate filament
      (IF) proteins lamin B1 and keratin 81. Association of lamin B1 with APC in
      cultured cells and human colonic tissue was verified by co-immunoprecipitation
      and colocalization. APC also colocalized with keratins and remained associated
      with IF proteins throughout a sequential extraction procedure. CONCLUSION: We
      introduce a versatile APC antibody that is useful for cell/tissue immunostaining,
      immunoblotting and immunoprecipitation. We also present evidence for interactions
      between APC and IFs, independent of actin filaments and microtubules. Our results
      suggest that APC associates with all three major components of the cytoskeleton,
      thus expanding potential roles for APC in the regulation of cytoskeletal
      integrity.

PMID- 19845968
TI  - Habitat stability and occurrences of malaria vector larvae in western Kenya
      highlands.
AB  - BACKGROUND: Although the occurrence of malaria vector larvae in the valleys of
      western Kenya highlands is well documented, knowledge of larval habitats in the
      uphill sites is lacking. Given that most inhabitants of the highlands actually
      dwell in the uphill regions, it is important to develop understanding of mosquito
      breeding habitat stability in these sites in order to determine their potential
      for larval control. METHODS: A total of 128 potential larval habitats were
      identified in hilltops and along the seasonal streams in the Sigalagala area of
      Kakamega district, western Kenya. Water availability in the habitats was followed
      up daily from August 3, 2006 to February 23, 2007. A habitat is defined as stable
      when it remains aquatic continuously for at least 12 d. Mosquito larvae were
      observed weekly. Frequencies of aquatic, stable and larvae positive habitats were
      compared between the hilltop and seasonal stream area using chi2-test. Factors
      affecting the presence/absence of Anopheles gambiae larvae in the highlands were
      determined using multiple logistic regression analysis. RESULTS: Topography
      significantly affected habitat availability and stability. The occurrence of
      aquatic habitats in the hilltop was more sporadic than in the stream area. The
      percentage of habitat occurrences that were classified as stable during the rainy
      season is 48.76% and 80.79% respectively for the hilltop and stream area.
      Corresponding frequencies of larvae positive habitats were 0% in the hilltop and
      5.91% in the stream area. After the rainy season, only 23.42% of habitat
      occurrences were stable and 0.01% larvae positive habitats were found in the
      hilltops, whereas 89.75% of occurrences remained stable in the stream area
      resulting in a frequency of 12.21% larvae positive habitats. The logistic
      regression analysis confirmed the association between habitat stability and
      larval occurrence and indicated that habitat surface area was negatively
      affecting the occurrence of An. gambiae larvae. While An. gambiae and An.
      funestus larvae occurred throughout the study period along the streams, a total
      of only 15 An. gambiae larvae were counted in the hilltops, and no An. funestus
      were found. Moreover, no larvae managed to develop into adults in the hilltops,
      and the density of adult An. gambiae was consistently low, averaging at 0.06
      females per house per survey. CONCLUSION: The occurrence of malaria vector larvae
      in the hilltop area was uncommon as a result of the low availability and high
      instability of habitats. To optimize the cost-effectiveness of malaria
      interventions in the western Kenya highlands, larval control should be focused
      primarily along the streams, as these are likely the only productive habitats at
      high altitude.

PMID- 19845969
TI  - Time course and dose response of alpha tocopherol on oxidative stress in
      haemodialysis patients.
AB  - BACKGROUND: Oxidative stress is associated with increased cardiovascular
      morbidity and mortality particularly in patients with end stage kidney disease.
      Although observational data from the general population has shown dietary
      antioxidant intake is associated with reduced cardiovascular morbidity and
      mortality, most clinical intervention trials have failed to support this
      relationship. This may be a consequence of not using an effective antioxidant
      dose and/or not investigating patients with elevated oxidative stress. The SPACE
      study, conducted in haemodialysis patients, reported that 800 IU/day of alpha
      tocopherol significantly reduced cardiovascular disease endpoints. A recent time
      course and dose response study conducted in hypercholesterolaemic patients that
      found 1600 IU/day of alpha tocopherol was an optimal dose. There is no such dose
      response data available for haemodialysis patients. Therefore the aim of this
      study is to investigate the effect of different doses of oral alpha tocopherol on
      oxidative stress in haemodialysis patients with elevated oxidative stress and the
      time taken to achieve this effect. METHODS: The study will consist of a time
      course followed by a dose response study. In the time course study 20
      haemodialysis patients with elevated oxidative stress will take either 1600
      IU/day natural (RRR) alpha tocopherol for 20 weeks or placebo. Blood will be
      collected every two weeks and analysed for a marker of oxidative stress (plasma
      F2-isoprostanes) and alpha tocopherol. The optimum time period to significantly
      decrease plasma F2-isoprostanes will be determined from this study. In the dose
      response study 60 patients will be randomised to receive either placebo, 100,
      200, 400, 800 or 1600 IU/day of natural (RRR) alpha tocopherol for a time period
      determined from the time course study. Blood will be collected at baseline and
      every two weeks and analysed for plasma F2-isoprostanes and alpha tocopherol. It
      is hypothesised that doses >/= 800 IU of vitamin E will be required to
      significantly decrease plasma F2-isoprostanes. DISCUSSION: This study will
      determine the time and dose required for alpha tocopherol to significantly
      decrease oxidative stress in haemodialysis patients. Data will be used to plan a
      large randomised controlled trial to assess the effects of alpha tocopherol on
      cardiovascular outcomes in haemodialysis patients. TRIAL REGISTRATION:
      ACTRN12609000608268.

PMID- 19845970
TI  - Amyloid-beta colocalizes with apolipoprotein B in absorptive cells of the small
      intestine.
AB  - BACKGROUND: Amyloid-beta is recognized as the major constituent of senile plaque
      found in subjects with Alzheimer's disease. However, there is increasing evidence
      that in a physiological context amyloid-beta may serve as regulating
      apolipoprotein, primarily of the triglyceride enriched lipoproteins. To consider
      this hypothesis further, this study utilized an in vivo immunological approach to
      explore in lipogenic tissue whether amyloid-beta colocalizes with nascent
      triglyceride-rich lipoproteins. RESULTS: In murine absorptive epithelial cells of
      the small intestine, amyloid-beta had remarkable colocalization with chylomicrons
      (Manders overlap coefficient = 0.73 +/- 0.03 (SEM)), the latter identified as
      immunoreactive apolipoprotein B. A diet enriched in saturated fats doubled the
      abundance of both amyloid-beta and apo B and increased the overlap coefficient of
      the two proteins (0.87 +/- 0.02). However, there was no evidence that abundance
      of the two proteins was interdependent within the enterocytes (Pearson's
      Coefficient < 0.02 +/- 0.03), or in plasma (Pearson's Coefficient < 0.01).
      CONCLUSION: The findings of this study are consistent with the possibility that
      amyloid-beta is secreted by enterocytes as an apolipoprotein component of
      chylomicrons. However, secretion of amyloid-beta appears to be independent of
      chylomicron biogenesis.

PMID- 19845971
TI  - Expression of endothelia and lymphocyte adhesion molecules in bronchus-associated
      lymphoid tissue (BALT) in adult human lung.
AB  - BACKGROUND: Bronchus-associated lymphoid tissue (BALT) is the secondary lymphoid
      tissue in bronchial mucosa and is involved in the development of bronchopulmonary
      immune responses. Although migration of lymphocytes from blood vessels into
      secondary lymphoid tissues is critical for the development of appropriate
      adaptive immunity, the endothelia and lymphocyte adhesion molecules that recruit
      specific subsets of lymphocytes into human BALT are not known. The aim of this
      study was to determine which adhesion molecules are expressed on lymphocytes and
      high endothelial venules (HEVs) in human BALT. METHODS: We immunostained frozen
      sections of BALT from lobectomy specimens from 17 patients with lung carcinoma
      with a panel of monoclonal antibodies to endothelia and lymphocyte adhesion
      molecules. RESULTS: Sections of BALT showed B cell follicles surrounded by T
      cells. Most BALT CD4+ T cells had a CD45RO+ memory phenotype. Almost all BALT B
      cells expressed alpha4 integrin and L-selectin. In contrast, 43% of BALT T cells
      expressed alpha4 integrin and 20% of BALT T cells expressed L-selectin. Almost
      all BALT lymphocytes expressed LFA-1. HEVs, which support the migration of
      lymphocytes from the bloodstream into secondary lymphoid tissues, were prominent
      in BALT. All HEVs expressed peripheral node addressin, most HEVs expressed
      vascular cell adhesion molecule-1, and no HEVs expressed mucosal addressin cell
      adhesion molecule-1. CONCLUSION: Human BALT expresses endothelia and lymphocyte
      adhesion molecules that may be important in recruiting naive and memory/effector
      lymphocytes to BALT during protective and pathologic bronchopulmonary immune
      responses.

PMID- 19845972
TI  - Genomic and epigenetic evidence for oxytocin receptor deficiency in autism.
AB  - BACKGROUND: Autism comprises a spectrum of behavioral and cognitive disturbances
      of childhood development and is known to be highly heritable. Although numerous
      approaches have been used to identify genes implicated in the development of
      autism, less than 10% of autism cases have been attributed to single gene
      disorders. METHODS: We describe the use of high-resolution genome-wide tilepath
      microarrays and comparative genomic hybridization to identify copy number
      variants within 119 probands from multiplex autism families. We next carried out
      DNA methylation analysis by bisulfite sequencing in a proband and his family,
      expanding this analysis to methylation analysis of peripheral blood and temporal
      cortex DNA of autism cases and matched controls from independent datasets. We
      also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex
      tissue by quantitative real-time polymerase chain reaction (PCR). RESULTS: Our
      analysis revealed a genomic deletion containing the oxytocin receptor gene, OXTR
      (MIM accession no.: 167055), previously implicated in autism, was present in an
      autism proband and his mother who exhibits symptoms of obsessive-compulsive
      disorder. The proband's affected sibling did not harbor this deletion but instead
      may exhibit epigenetic misregulation of this gene through aberrant gene silencing
      by DNA methylation. Further DNA methylation analysis of the CpG island known to
      regulate OXTR expression identified several CpG dinucleotides that show
      independent statistically significant increases in the DNA methylation status in
      the peripheral blood cells and temporal cortex in independent datasets of
      individuals with autism as compared to control samples. Associated with the
      increase in methylation of these CpG dinucleotides is our finding that OXTR mRNA
      showed decreased expression in the temporal cortex tissue of autism cases matched
      for age and sex compared to controls. CONCLUSION: Together, these data provide
      further evidence for the role of OXTR and the oxytocin signaling pathway in the
      etiology of autism and, for the first time, implicate the epigenetic regulation
      of OXTR in the development of the disorder.See the related commentary by Gurrieri
      and Neri: http://www.biomedcentral.com/1741-7015/7/63.

PMID- 19845973
TI  - Defective oxytocin function: a clue to understanding the cause of autism?
AB  - The autism spectrum disorders are a group of conditions with neurobehavioral
      impairment affecting approximately 0.6% of children. The clinical presentation is
      complex and the etiology is largely unknown, although a major role of genetic
      factors is widely accepted. A number of genetic studies led to the identification
      of genes and/or copy number variants whose alterations are associated with
      autism, but no specific factor has been found so far to be responsible for a
      substantial proportion of cases. Epigenetic modifications may also play a role,
      as demonstrated by the occurrence of autism in genetic conditions caused by
      mutations in imprinted genes or regions.The article by Gregory et al. published
      this month in BMC Medicine, reports on genomic and epigenetic alterations of
      OXTR, the gene encoding the receptor for oxytocin. The involvement of this gene
      was suggested by its deletion in an autistic patient. The subsequent analysis of
      a group of unrelated autistic subjects did not show an OXTR deletion, but rather
      hypermethylation of the gene promoter, with a reduced mRNA expression.These
      findings address two major points of the current debate on the etiology and
      pathogenesis of autism: the role of oxytocin, known to be involved in modeling
      human behavior, and the possible involvement of epigenetic mechanisms. The nature
      of this epigenetic dysregulation is unknown but, if proved to be true, might
      explain the failure to identify sequence alterations in a host of candidate
      genes. Practical implications of these findings may be forthcoming, however not
      before extension and validation on a larger scale have confirmed their value.See
      the associated research paper by Gregory et al: http://www.biomedcentral.com/1741
      7015/7/62.

PMID- 19845974
TI  - Cost-effectiveness of interventions based on physical exercise in the treatment
      of various diseases: a systematic literature review.
AB  - OBJECTIVES: The aim of this study was to review studies reporting cost
      effectiveness of exercise-based interventions in treatment of various diseases.
      METHODS: Systematic literature search using several databases. Abstracts
      initially screened independently by two authors, full-text articles again
      evaluated by two authors, who decided whether an article should be included.
      Included were scientifically valid articles describing controlled studies that
      included an exercise-based intervention in the treatment of an established
      medical condition, and also reported on the cost-effectiveness of the
      intervention, or its effect on the utilization of health services. Quality was
      assessed with an established approach. RESULTS: A total of 914 articles were
      identified, of them 151 were obtained for closer review. Sixty-five articles
      describing sixty-one studies were included. Most (82 percent) were randomized
      trials. Twenty-eight studies dealt with musculoskeletal disorders, fifteen with
      cardiology, four with rheumatic diseases, four with pulmonary diseases, three
      with urinary incontinence, and two with vascular disorders. There was one study
      each in the fields of oncology, chronic fatigue, endocrinology, psychiatry, and
      neurology. Exercise interventions in musculoskeletal disorders were deemed to be
      cost-effective in 54 percent, in cardiology in 60 percent, and in rheumatic
      diseases in 75 percent of the cases. There was some evidence that exercise might
      be cost-effective in intermittent claudication, breast cancer patients, diabetes,
      and schizophrenia. CONCLUSIONS: The number of studies assessing cost
      effectiveness of exercise interventions in various diseases is still limited. The
      results show large variation but suggest that some exercise interventions can be
      cost-effective. Most convincing evidence was found for rehabilitation of cardiac
      and back pain patients; however, even in these cases, the evidence was partly
      contradictory.

PMID- 19845975
TI  - The feasibility of harmonizing health technology assessments across
      jurisdictions: a case study of drug eluting stents.
AB  - OBJECTIVES: There is considerable interest in the potential for harmonizing
      health technology assessments (HTA) across jurisdictions. This study aims to
      consider four HTAs of drug eluting stents to determine the degree to which the
      methods adopted, evidence considered, and resulting recommendations diverge.
      METHODS: Four HTAs of drug eluting stents were selected for inclusion and
      evaluated using a framework developed to systematically capture information on
      the process adopted, the evidence considered and the recommendations of each HTA.
      RESULTS AND CONCLUSIONS: The findings suggest that, although there is a common
      core data set considered by most of the agencies, differences in the approach to
      HTA, heterogeneity of studies, and the limited relevance of research findings to
      local practice meant that the core data set had only limited influence on the
      resulting recommendations. Of the HTA agencies considered in the analysis, many
      sought to generate additional primary research from local settings to help inform
      the development of recommendations that were relevant to local practice. This
      raises questions about the extent to which HTA methods can be harmonized across
      jurisdictions.

PMID- 19845976
TI  - Ethics in Canadian health technology assessment: a descriptive review.
AB  - BACKGROUND: Despite the mandate to examine the medical, ethical, and economic
      implications of the development and use of health technology, health technology
      assessment (HTA) reports often emphasize the epidemiologic and economic aspects,
      and omit ethical considerations. This study examines both whether and how ethical
      issues are incorporated into HTA. OBJECTIVES: We aim to (i) review a set of
      Canadian HTA reports for ethics content, (ii) describe the strategies used to
      incorporate ethically relevant information into HTA, and (iii) determine the
      presence of implicit ethical issues in a sample of HTA reports. METHODS:
      Descriptive and qualitative content analysis of 608 HTA reports produced by six
      Canadian HTA agencies from January 1997 to December 2006. RESULTS: We found that
      (i) a minority (17 percent) of Canadian HTA reports addressed ethical issues,
      (ii) secondary research predominates while primary analysis is rare, (iii)
      implicit ethical issues are present in HTA reports that do not purport to address
      ethics. CONCLUSIONS: Canadian HTA reports rarely explicitly, and then only
      superficially, address ethics, though implicit ethical issues abound.

PMID- 19845977
TI  - Systematic review of economic evidence for the detection, diagnosis, treatment,
      and follow-up of colorectal cancer in the United Kingdom.
AB  - OBJECTIVES: The aim of this study was to examine the availability and consistency
      of economic evidence for the detection, diagnosis, treatment, and follow-up of
      colorectal cancer. METHODS: A systematic review of UK economic evaluations of
      colorectal cancer interventions was undertaken. Searches were undertaken across
      ten electronic databases. Studies were critically appraised through reference to
      a conceptual model of UK colorectal cancer services. RESULTS: Forty-seven studies
      met the inclusion criteria. There is a substantial economic evidence base
      surrounding population-level colorectal screening, surgical procedures, and
      cytotoxic therapies for the adjuvant and palliative treatment of colorectal
      cancer. There is limited evidence concerning the diagnosis of suspected
      colorectal cancer, curative treatments for metastatic disease and follow-up
      regimens for nonmetastatic disease. No studies were identified relating to the
      economics of radiotherapy, surveillance of increased-risk groups, end-of-life
      care, or the management of hereditary colorectal cancer. Where evidence is
      available, studies are subject to important differences concerning treatment
      options, decision criteria, and incongruent assumptions concerning the disease
      and its management. CONCLUSIONS: Across many aspects of the colorectal cancer
      service, current practice appears to have emerged without the consideration or
      support of economic evidence. There is a need to develop a common understanding
      how colorectal cancer models should be structured and implemented.

PMID- 19845978
TI  - Quality of trials reported as conference abstracts in China: how well are they
      reported?
AB  - OBJECTIVES: Clear, transparent, and sufficiently detailed abstracts of journal
      articles and conference abstracts are important because readers often base their
      assessment of a trial on such information. There are concerns over the
      reliability and quality of trials published only in the proceedings of scientific
      meetings. This study aims to assess the reporting quality of abstracts of
      randomized trials published in Chinese medical conference abstracts. METHODS:
      Conference abstracts reporting randomized trials included in the China National
      Knowledge Infrastructure (CNKI) in 2007 were identified. A revised checklist
      (based on the CONSORT extension for reporting randomized controlled trials in
      journal and conference abstracts) was used to assess the reporting quality of
      these conference abstracts. RESULTS: A total of 567 conference abstracts of
      randomized trials were identified. Some aspects were well reported, including 94
      percent of authors contact details, 83 percent of trial interventions and 78
      percent of control interventions, 62 percent of participant eligibility criteria,
      and 66 percent the number of participants randomized to each group. Other areas
      were very poorly reported: only 1 percent identified the study as randomized in
      the abstract title, 2 percent reported the trial design, and only 7 percent
      reported on blinding. No details of allocation concealment, trial registration,
      or funding were reported. CONCLUSION: The information given for trials in
      conference proceedings in China is very poor, especially in some aspects of
      methodological quality, trial registration, and funding source. The quality of
      conference abstracts for trials should be improved to further facilitate
      understanding of their conduct and validity.

PMID- 19845979
TI  - Economic evaluation of a minimal psychological intervention in chronically ill
      elderly patients with minor or mild to moderate depression: a randomized trial
      (the DELTA-study).
AB  - OBJECTIVES: Depression is associated with high healthcare utilization and related
      costs. Effective treatments might reduce the economic burden. The objective of
      this study was to establish the cost-utility of a minimal psychological
      intervention (MPI) aimed at reducing depression and improving quality of life in
      elderly persons with diabetes or chronic obstructive pulmonary disease and co
      occurring minor, mild, or moderate depression. METHODS: Trial-based cost-utility
      analysis was used to compare the MPI with usual care. Annual costs and quality
      adjusted life-years (QALYs) based on the Euroqol (EQ5D) and on depression-free
      days were calculated. RESULTS: Annual costs and effects were not significantly
      different for the MPI group and care as usual. Bootstrap analysis indicated a
      dominant intervention, with a probability of 63 percent that the MPI is less
      costly and more effective than usual care. CONCLUSIONS: The cost-effectiveness
      analysis does not support dissemination of the MPI in its current form. The
      economic evaluation study showed limited probability that MPI is cost-effective
      over usual care. Further adjustments to the MPI are needed to make the
      intervention suitable for dissemination in regular care. TRIAL REGISTRATION:
      isrctn.org, identifier: ISRCTN92331982.

PMID- 19845980
TI  - Costs and effects of using specialized breast technologists in prereading
      mammograms in a clinical patient population.
AB  - OBJECTIVES: The aim of this study was to assess the costs and effects of using
      specialized breast technologists in prereading mammograms to reduce the
      increasing workload of radiologists in daily clinical practice. Mammography is
      the most widely used imaging modality for early detection and diagnosis of breast
      cancer. METHODS: A total of 1389 mammograms of consecutive patients were
      evaluated by two technologists trained in mammogram interpretation. The costs and
      effects of four different experimental strategies of prereading mammograms by
      technologists were analyzed by decision analytic modeling and compared with the
      conventional strategy of standard evaluation by the radiologist on duty. RESULTS:
      Overall, the employment of technologists in this patient population resulted in a
      potential time saving up to 73 percent (1019/1389) for the radiologist. No
      additional false-negative imaging results were found as compared to the
      conventional strategy. The total diagnostic costs in the conventional strategy
      were determined at euro150,602. The experimental strategies resulted in cost
      savings up to 17.2 percent (range, euro122,494-euro139,781). CONCLUSIONS: The
      employment of technologists in prereading mammograms in a clinical patient
      population could be effective to reduce the workload of radiologists without
      jeopardizing the detection of malignancies. Furthermore, diagnostic costs can be
      reduced considerably.

PMID- 19845981
TI  - Developing medical device technologies from users' perspectives: a theoretical
      framework for involving users in the development process.
AB  - OBJECTIVES: The aim of this study was to suggest an acceptable and generic
      theoretical framework for involving various types of users in the medical device
      technology (MDT) development process (MDTDP). METHODS: The authors propose a
      theoretical framework suggesting different routes, methods and stages through
      which various types of medical device users can be involved in the MDTDP.
      RESULTS: The suggested framework comprises two streams of users' involvement in
      MDT development, that is, what might be called the end users' stream and the
      professional users' stream for involving these two groups respectively in the
      process of developing both simple and more complex and innovative medical devices
      from conceptualization through to the market deployment. This framework suggests
      various methods that can be used for users' involvement at different stages of
      the MDT lifecycle. To illustrate the application of the framework, several MDT
      development scenarios and device exemplars are presented. CONCLUSIONS:
      Development of medical devices from users' perspectives requires not only the
      involvement of healthcare professionals but also that of the ultimate end users,
      that is, patients, people with disabilities and/or special needs, and their
      caregivers. The evidence shows that such end users quickly discard devices that
      do not fulfill their personal expectations, even though both manufacturers and
      healthcare professionals may consider those end users' requirements met.
      Developers and manufacturers need to recognize this potent potential discrepancy
      between the parties involved, and involve end users and professional healthcare
      staff directly in the MDTDP. The framework, the authors contend, is a step
      forward in helping medical device manufacturers plan and make decisions about
      users' involvement at different stages of the MDTDP.

PMID- 19845982
TI  - How well do search filters perform in identifying economic evaluations in MEDLINE
      and EMBASE.
AB  - OBJECTIVES: Health technology assessment (HTA) agencies assessing the cost
      effectiveness of healthcare technologies seek evidence from economic evaluations.
      As well as searching economic evaluation databases, researchers often search
      MEDLINE and EMBASE, using search filters whose current performance is unclear. We
      assessed the performance of search filters in identifying economic evaluations
      from MEDLINE and EMBASE. METHODS: A gold standard of economic evaluations was
      compiled from National Health Service Economic Evaluation Database (NHS EED)
      records for 2000, 2003, and 2006. Corresponding records were retrieved in MEDLINE
      and EMBASE. Search filters were identified from the InterTASC Information
      Specialists' SubGroup Web site and from Canadian Agency for Drugs and
      Technologies in Health (CADTH) Information Services. The sensitivity and
      precision of search filters in retrieving gold standard records from MEDLINE and
      EMBASE were tested. RESULTS: A total of 2,070 full economic evaluations were
      identified from NHS EED. Of these, 1,955 records were available in Ovid MEDLINE
      and 1,873 were available in Ovid EMBASE. Thirteen MEDLINE and eight EMBASE
      filters were identified. NHS Quality Improvement Scotland (full and brief
      filters), the NHS EED and Royle and Waugh filters achieved over 0.99 sensitivity
      in MEDLINE. NHS Quality Improvement Scotland, CADTH, Royle and Waugh, and NHS EED
      filters achieved greater than 0.99 sensitivity in EMBASE. Filters demonstrated
      low precision. CONCLUSIONS: This research provided new performance data on search
      filters to identify economic evaluations in MEDLINE and EMBASE. It demonstrated
      that highly sensitive economic evaluation filters are available, but that
      precision is low, yielding perhaps 5 relevant records per 100 records scanned.

PMID- 19845983
TI  - Organizational and patient-related assessments in HTAs: state of the art.
AB  - OBJECTIVES: The use and implementation of health technologies do influence and
      are influenced by organizational structures and processes as well as patient's
      experiences and actions. The objective of this study is to discuss the content
      and managing of organizational and patient-related assessments in HTAs. METHODS:
      Quantitative and qualitative analysis were performed based on a review of
      organizational and patient-related assessments included in a random sample of
      fifty HTA reports. The reports were identified from INAHTA members' Web sites
      where homepages of HTA agencies where searched for full HTA reports, published in
      English or Scandinavian languages. RESULTS: HTA reports including organizational
      assessments mainly comprised issues related to process and structure, while
      issues such as control and evaluation of the technology were included less often.
      Cultural and environmental issues were included in a little over half of the
      reports. Reports including patient-related assessments mainly comprised
      psychological issues. Patients' perceptions of the technology's effect on their
      health, patient-information, and social and ethical issues were included less
      often. Few reports included implications for the patient's significant others.
      There was considerable variation in how comprehensive the issues were managed as
      there was in the methodological transparency of the HTA reports. CONCLUSIONS:
      There is room for improvement in the assessments of organizational and patient
      related issues. Absence of a description of the considerations made when
      determining the content and methods of the assessments limits the usefulness of
      an HTA. The reader is left uncertain of the relevance and validity of the
      organizational and patient-related assessments.

PMID- 19845984
TI  - Complementing the net benefit approach: a new framework for Bayesian cost
      effectiveness analysis.
AB  - OBJECTIVES: The aim of cost-effectiveness analysis is to maximize health benefits
      from a given budget, taking a societal perspective. Consequently, the comparison
      of alternative treatments or technologies is solely based on their expected
      effectiveness and cost. However, the expectation, or mean, poses important
      limitations as it might be a poor summary of the underlying distribution, for
      instance when the effectiveness is a categorical variable, or when the
      distributions of either effectiveness or cost present a high degree of asymmetry.
      Clinical variables often present these characteristics. METHODS: In this study,
      we present a framework for cost-effectiveness analysis based on the whole
      posterior distribution of effectiveness and cost. RESULTS: An application with
      real data is included to illustrate the analysis. Decision-making measures such
      as the incremental cost-effectiveness ratio, incremental net-benefit, and cost
      effectiveness acceptability curves, can also be defined under the new framework.
      CONCLUSIONS: This framework overcomes limitations of the mean and offers
      complementary information for the decision maker.

PMID- 19845985
TI  - Handling uncertainty in economic evaluations of patient level data: a review of
      the use of Bayesian methods to inform health technology assessments.
AB  - OBJECTIVES: Due to potential advantages (e.g., using all available evidence),
      Bayesian methods have been proposed to assist healthcare decision making. This
      review provides a detailed description of how Bayesian methods have been applied
      to economic evaluations of patient level data. The results serve both as a
      reference and as a means by which to examine the appropriate application of
      Bayesian methods to inform decision making. METHODS: MEDLINE, EMBASE, and
      Cochrane Economic Evaluation databases were searched to identify studies,
      published up to November 2007, meeting three inclusion criteria: (i) the study
      conducted an economic evaluation, (ii) sampling uncertainty was incorporated
      using Bayesian methods, (iii) the likelihood function was informed by patient
      level data from a single source. Data were collected on key study characteristics
      (e.g., prior distribution, likelihood function, presentation of uncertainty).
      RESULTS: The search identified 366 potentially relevant studies, from which 103
      studies underwent full-text review. Sixteen studies met the inclusion criteria.
      Half of the studies used uninformative priors; most studies incorporated the
      potential dependence between costs and effects, and presented cost-effectiveness
      acceptability curves. Results were sensitive to changes in the priors and
      likelihoods. CONCLUSIONS: Limited use of informative priors, among the included
      studies, gives policy makers little guidance on one of the main benefits of
      Bayesian methods, the ability to integrate all available evidence to capture the
      uncertainty inherent in decision making.

PMID- 19845986
TI  - Using information graphics in health technology assessment: toward a structured
      approach.
AB  - OBJECTIVES: This study investigates the use of information graphics to display
      the outputs of health technology assessment (HTA) in the United Kingdom and
      proposes a more structured approach founded in an analysis of the decision-making
      requirements of the key stakeholders. METHODS: A scoping review of HTA reports
      was conducted to investigate current practice in the use of information graphics
      in HTA literature. A classification framework using dimensions of report section,
      graphical type, and originating research center was devised and used for a full
      content analysis of the graphical figures in the fifty most recent reports
      produced for the UK National Health Service's HTA process. RESULTS: Our survey
      shows that graphical tools are used extensively in HTA reports although less
      frequently than tables. Use of information graphics varies widely between
      different report sections and tends to follow conventional lines with little
      evidence of variance from established practice. The largest variance was found
      between the quantities of graphics used by different research centers responsible
      for authoring the reports. CONCLUSIONS: HTA makes extensive use of graphics;
      however, there is little evidence of a systematic or standardized approach, or of
      much innovation. Significant potential exists to explore the application of
      information graphics in this field, but there are many research challenges. A
      contextually based, structured approach to the design of effective information
      graphics in HTA is proposed as a basis both to investigate the application of
      existing graphical tools in HTA, and to explore the considerable scope for
      innovation.

PMID- 19845987
TI  - Knowledge network for medical technology management in Mexico.
AB  - OBJECTIVES: The role of biomedical engineers (BMEs) has changed widely over the
      years, from managing a group of technicians to the planning of large
      installations and the management of medical technology countrywide. As the
      technology has advanced, the competence of BMEs has been challenged because it is
      no longer possible to be an expert in every component of the technology involved
      in running a hospital. Our approach has been to form a network of professionals
      that are experts in different fields related to medical technology, where work is
      coordinated to provide high quality services at the planning and execution stages
      of projects related to medical technology. METHODS: A study of the procedures
      involved in the procurement of medical technology has been carried out over the
      years. These experiences have been compared with several case studies where the
      approach to problem solving in this area has been multidisciplinary. Planning and
      execution phases of projects involving medical technology management have been
      identified. RESULTS: After several instances of collaboration among experts from
      different fields, a network for management of healthcare technology has been
      formed at our institution that incorporates the experience from different
      departments that were dealing separately with projects involving medical
      technology. CONCLUSIONS: This network has led us to propose this approach to
      solve medical technology management projects, where the strengths of each
      subgroup complement each other. This structure will lead to a more integrated
      approach to healthcare technology management and will ensure higher quality
      solutions.

PMID- 19845988
TI  - A content analysis of Health Technology Assessment programs in Latin America.
AB  - OBJECTIVES: Health Technology Assessment (HTA) is a relatively new concept in
      Latin America (LA). The objectives of this exploratory study were to identify HTA
      programs in LA, review HTA documents produced by those programs, and assess the
      extent to which HTA aims are being achieved. METHODS: An electronic search
      through two databases was performed to identify HTA programs in LA. A content
      analysis was performed on HTA documents (n = 236) produced by six programs
      between January 2000 and March 2007. Results were analyzed by comparing document
      content with the main goals of HTA. RESULTS: The number of HTA documents
      increased incrementally during the study period. The documents produced were
      mostly short HTA documents (82 percent) that assessed technologies such as drugs
      (31 percent), diagnostic and/or screening technologies (18 percent), or medical
      procedures (18 percent). Two-thirds (66 percent) of all HTA documents addressed
      issues related to clinical effectiveness and economic evaluations. Ethical,
      social, and/or legal issues were rarely addressed (<1 percent). The two groups
      most often targeted for dissemination of HTA information were third-party payers
      (55 percent) or government policy makers (41 percent). CONCLUSIONS: This study
      showed that while HTA programs in LA have attempted to address the main goals of
      HTA, they have done so through the production of short documents that focus on
      practical high-technology areas of importance to two specific target groups.
      Clinical and economic considerations still take precedence over ethical, social,
      and/or legal issues. Thus, an integrated conceptual framework in LA is wanting.

PMID- 19845989
TI  - Magnetic resonance imaging, knee arthroscopy, and clinical decision making: a
      descriptive study of five surgeons.
AB  - OBJECTIVES: A randomized controlled trial (RCT) showed magnetic resonance imaging
      for patients waiting for knee arthroscopy did not reduce the number of
      arthroscopies. Our study aimed to identify decisions made by orthopedic surgeons
      about whether patients on a waiting list should proceed to arthroscopy, and to
      describe surgeons' decisions. METHODS: Five surgeons were asked to Think Aloud
      (TA) as they made their decisions for twelve patients from the original RCT.
      Audiotapes of the decision making were transcribed for analysis. RESULTS: For
      five patients, surgeons agreed about proceeding with arthroscopy, although
      reasoning differed. In no cases did surgeons agree about not proceeding to
      arthroscopy. Agreement was more likely in patients with clinically diagnosed
      meniscal abnormality, and less likely in patients with osteoarthritis.
      CONCLUSIONS: Surgeons' decisions were influenced by patient wishes. For some
      patients, the decision to proceed with arthroscopy was based solely on clinical
      diagnosis; MRI may not be advantageous in these instances. Surgeons disagreed
      more often than they agreed about the decision to proceed with arthroscopy,
      particularly when OA was diagnosed. This has implications for decision making in
      the current NHS patient choice environment. Patients may choose a treatment
      provider from a list of available providers at time of original clinical
      assessment and diagnosis. The treating surgeon does not necessarily re-examine
      the patient until the day of surgery. Given the variation between surgeons about
      the merits of proceeding with arthroscopy, surgeons may end up in the invidious
      position of providing surgery to patients whom they do not believe will benefit
      from arthroscopy.

PMID- 19845990
TI  - Cost-effectiveness of prophylaxis against on-demand treatment in boys with severe
      hemophilia A in Iran.
AB  - OBJECTIVE: The aim of this study was to assess the incremental cost-effectiveness
      of on-demand versus prophylactic hemophilia therapy in Iran from a third-party
      payers' perspective. METHODS: A retrospective chart review of twenty-five type A
      hemophiliacs who were treated in three hemophilia treatment centers was
      conducted. The patients were boys 0-9 years old receiving one of two treatments:
      (i) prophylaxis with concentrate at clinic; (ii) concentrate at clinic as on
      demand. Fourteen boys received on-demand infusions for bleeding events, and
      eleven boys received infusions prophylaxis. Data were extracted from documents in
      the hemophilia treatment centers during a period of approximately 6 months.
      RESULTS: The patients receiving prophylactic treatment had fewer bleeding events
      each month (mean, 0.26 versus 2.74) but used more concentrate (225.31 versus
      87.20 units/kg per month). Average monthly cost per patient in the prophylaxis
      group was approximately 1.9 times higher than in the on-demand group. Compared
      with on-demand infusion, prophylaxis costs 3,201,656 Rials (euro213.45) per
      bleeding event prevented. CONCLUSION: Prophylactic care markedly reduces the
      number of bleeding episodes, but at considerable cost.

PMID- 19845991
TI  - Self-report versus care provider registration of healthcare utilization: impact
      on cost and cost-utility.
AB  - OBJECTIVES: This study aims to compare the impact of two different sources of
      resource use, self-report versus care provider registrations, on cost and cost
      utility. METHODS: Data were gathered for a cost-effectiveness study performed
      alongside a 2-year randomized controlled trial evaluating the effect of an
      INTERdisciplinary COMmunity-based management program (INTERCOM) for patients with
      chronic obstructive pulmonary disease (COPD). The program was offered by
      physiotherapists, dieticians and respiratory nurses. During the 2-year period,
      patients reported all resource use in a cost booklet. In addition, data on
      hospital admissions and outpatient visits, visits to the physiotherapist,
      dietician or respiratory nurse, diet nutrition, and outpatient medication were
      obtained from administrative records. The cost per quality-adjusted life-year
      (QALY) was calculated in two ways, using data from the cost booklet or
      registrations. RESULTS: In total, 175 patients were included in the study.
      Agreement between self-report and registrations was almost perfect for
      hospitalizations (rho = 0.93) and physiotherapist visits (rho = 0.86), but above
      0.55, moderate, for all other types of care. The total cost difference between
      the registrations and the cost booklet was 464 euros with the highest difference
      for hospitalizations 386 euro. Based on the cost booklet the cost difference
      between the treatment group and usual care was 2,444 euros (95 percent confidence
      interval [CI], -819 to 5,950), which resulted in a cost-utility of 29,100
      euro/QALY. For the registrations, the results were 2,498 euros (95 percent CI, 
      88 to 6,084) and 29,390 euro/QALY, respectively. CONCLUSIONS: This study showed
      that the use of self-reported data or data from registrations effected within
      group costs, but not between-group costs or the cost utility.

PMID- 19845992
TI  - Development of health technology assessment in Central Europe.

PMID- 19845993
TI  - Point-source outbreak of coccidioidomycosis in construction workers.
AB  - Coccidioidomycosis results from inhaling spores of the fungus Coccidioides spp.
      in soil or airborne dust in endemic areas. We investigated an outbreak of
      coccidioidomycosis in a 12-person civilian construction crew that excavated soil
      during an underground pipe installation on Camp Roberts Military Base, California
      in October 2007. Ten (83.3%) workers developed symptoms of coccidioidomycosis;
      eight (66.7%) had serologically confirmed disease, seven had abnormal chest
      radiographs, and one developed disseminated infection; none used respiratory
      protection. A diagnosis of coccidioidomycosis in an eleventh worker followed his
      exposure to the outbreak site in 2008. Although episodic clusters of infections
      have occurred at Camp Roberts, the general area is not associated with the high
      disease rates found in California's San Joaquin Valley. Measures to minimize
      exposure to airborne spores during soil-disrupting activities should be taken
      before work begins in any coccidioides-endemic area, including regions with only
      historic evidence of disease activity.

PMID- 19845994
TI  - Epidemiology and characterization of Staphylococcus epidermidis isolates from
      humans, raw bovine milk and a dairy plant.
AB  - Geographically related Staphylococcus epidermidis isolates from human patients
      (n=30), dairy farms (farmers and individual raw milk from cattle, n=36) and a
      dairy plant (n=55) were examined for epidemiological relatedness by pulsed-field
      gel electrophoresis and, using in vitro methods, for the ability to produce
      biofilm and antimicrobial resistance. Methicillin-resistant isolates (MRSE) were
      also identified and characterized. Isolates from farmers and dairy cattle were
      found to be genetically related, while isolates from human patients were highly
      diverse. Some dairy plant isolates (18.2%) were closely related to those from
      dairy farms. Biofilm production and resistance to antimicrobial agents were most
      typical for isolates from human patients, of which 76.7% were MRSE. Methicillin
      resistance was also widespread in farm-related isolates (61.1%). This study
      indicates the possible transmission of S. epidermidis between cattle and farmers.
      Dairy products were not proven to be an important source of either human
      infections or methicillin-resistant strains.

PMID- 19845995
TI  - The epidemiology of primary amoebic meningoencephalitis in the USA, 1962-2008.
AB  - Naegleria fowleri, a free-living, thermophilic amoeba ubiquitous in the
      environment, causes primary amoebic meningoencephalitis (PAM), a rare but nearly
      always fatal disease of the central nervous system. While case reports of PAM
      have been documented worldwide, very few individuals have been diagnosed with PAM
      despite the vast number of people who have contact with fresh water where N.
      fowleri may be present. In the USA, 111 PAM case-patients have been prospectively
      diagnosed, reported, and verified by state health officials since 1962.
      Consistent with the literature, case reports reveal that N. fowleri infections
      occur primarily in previously healthy young males exposed to warm recreational
      waters, especially lakes and ponds, in warm-weather locations during summer
      months. The annual number of PAM case reports varied, but does not appear to be
      increasing over time. Because PAM is a rare disease, it is challenging to
      understand the environmental and host-specific factors associated with infection
      in order to develop science-based, risk reduction messages for swimmers.

PMID- 19845996
TI  - Evaluation of interventions and vaccination strategies for low pathogenicity
      avian influenza: spatial and space-time analyses and quantification of the spread
      of infection.
AB  - In recent years the control of low pathogenicity avian influenza (LPAI) viruses
      of the H5 and H7 subtypes has increasingly become a concern. We evaluated the
      measures (stamping out, controlled marketing, emergency and preventive
      vaccination, farm density reduction and restocking in homogenous areas)
      implemented to control the LPAI epidemics that occurred in Italy between 2000 and
      2005, using a combination of spatial and space-time analyses and estimates of the
      basic reproduction ratio (R0). Clustering of infected farms decreased over the
      years, indicating the effectiveness of the control strategies implemented.
      Controlled marketing [relative risk (RR) 0.46, 95% confidence interval (CI) 0.27
      0.80], emergency (RR 0.47, 95% CI 0.39-0.57) and preventive vaccination (RR 0.19,
      95% CI 0.09-0.41) were the most effective measures, yet R0<1 was only for
      preventive vaccination. Our results are useful for identifying the most effective
      measures for reducing the risk of the spread of LPAI and optimizing the
      allocation of resources.

PMID- 19845997
TI  - Emergence and disappearance of W135 meningococcal disease.
AB  - W135 meningococcal disease was imported into Singapore in 2000 via Hajj pilgrims.
      Previous studies have showed sustained carriage of W135 with the potential for
      further transmission within communities. We therefore set out to determine
      whether W135 meningococcal disease would become endemic in Singapore after its
      introduction in 2000. Cases occurred until 2003, but no further cases have been
      reported since 2004.

PMID- 19845998
TI  - Temporal and farm-management-associated variation in the faecal-pat prevalence of
      Campylobacter jejuni in ruminants.
AB  - In a 2-year longitudinal study of adult animals on 15 dairy farms and four sheep
      farms in Lancashire, UK. C. jejuni was isolated from all farms, although not on
      every occasion. Faecal samples were collected and cultured using standard
      techniques for isolation of Campylobacter. Assignment to species was via PCR
      assays. Peak prevalence of C. jejuni in both cattle and sheep was observed during
      the summer and in cattle this apparent seasonality was associated with grazing
      pasture [odds ratio (OR) 2.14], while in sheep it was independent of grazing.
      Increased prevalence was associated with increased milk yield (OR 1.05) and herd
      size (OR 1.01) in dairy cattle, and with increased stocking density (OR 1.29) and
      pasture quality (OR 2.16) in sheep. There was considerable variation in
      prevalence between farms but no evidence of large-scale spatial variation. The
      association between C. jejuni prevalence and diet in dairy cattle deserves
      further investigation.

PMID- 19845999
TI  - [Beware the influence of artificial ventilation on monitoring with pulse
      indicator continuous cardiac output].

PMID- 19846000
TI  - [Non-invasive positive pressure ventilation in patients with acute hypoxemic
      respiratory failure: a prospective cohort study].
AB  - OBJECTIVE: To investigate the clinical effect of non-invasive positive pressure
      ventilation (NPPV) on acute hypoxemic respiratory failure (AHRF), and to look for
      predictors of failure of NPPV in patients with AHRF. METHODS: In the cohort
      study, the clinical data of patients with AHRF in respiratory intensive care unit
      (RICU) of Beijing Chaoyang Hospital from January 2004 to December 2007 were
      collected prospectively. Patients were divided into successful group and failure
      group according to outcome of NPPV. Basic clinical information, NPPV mode and
      duration, vital signs, arterial blood gas analysis, and oxygenation index
      (PaO(2)/FiO(2)) before and 2 hours, 24 hours after NPPV were analyzed and
      compared between two groups. RESULTS: (1)The NPPV successful rate in 59 cases was
      62.7% (37/59). (2)Compared with failure group, mean age, the ratio of patients in
      whom respiratory failure were induced by pulmonary infection were lower in
      successful group (both P<0.01). There was no difference in PaO(2)/FiO(2)between
      two groups before NPPV, but PaO(2)/FiO(2) in successful group was markedly higher
      than those of failure group after 2 hours and 24 hours of NPPV (P<0.05 and
      P<0.01), while heart rate (HR), respiratory rate (RR) were significantly lower
      (all P<0.01). (3)Logistic regression analysis identified age > or = 60 years
      [odds ratio (OR) 8.30, 95% confidence interval (CI) 2.49-27.60, P=0.002],
      pulmonary infection as underlying disease of respiratory failure (OR 6.19, 95%CI
      1.90-20.20, P=0.027), PaO(2)/FiO(2)<150 mm Hg (1 mm Hg=0.133 kPa) after 2 hours
      of NPPV (OR 3.65, 95%CI 1.20-11.04, P=0.044), HR>100 times/min after 24 hours of
      NPPV (OR 7.45, 95%CI 2.15-25.58, P=0.010), and RR>30 times/min after 24 hours of
      NPPV (OR 7.26, 95%CI 1.88-24.49, P=0.018) as risk factors independently
      associated with failure of NPPV. CONCLUSION: NPPV can be the first line treatment
      for severe AHRF patients without absolute contraindication, while patients of
      older age with pulmonary infection, the risk of failure of NPPV is higher. Lack
      of improvement in cardiorespiratory and oxygenation condition after a short
      period of NPPV is the predictor of NPPV failure.

PMID- 19846001
TI  - [Effect of positive end-expiratory pressure on the pressure gradient of venous
      return in hypovolemic patients under mechanical ventilation].
AB  - OBJECTIVE: To assess the effects of positive end-expiratory pressure (PEEP) on
      central venous pressure (CVP) and common iliac venous pressure (CIVP), and the
      difference between CVP and CIVP [D(c-i)VP] in hypovolemic patients under
      mechanical ventilation. METHODS: From May 2007 to May 2009, 30 acute hypovolemic
      adult patients undergoing mechanical ventilation in intensive care unit (ICU)
      were enrolled. The patients were randomly divided into three groups, and PEEP
      with 0, 5, 10 cm H(2)O (1 cm H(2)O=0.098 kPa) levels were used respectively. Ten
      mechanically ventilated patients with similar basic clinical conditions but
      normal blood volume were selected randomly as the control group. CVP, CIVP and
      D(c-i)VP were measured and recorded at each PEEP level in both groups. The
      patients' heart rate, mean artery pressure and respiratory pressure data were
      also collected. The correlation analysis was used to analyze relationship between
      CVP and CIVP and between the changes in venous pressure and the changes in
      respiratory pressure. RESULTS: (1)CVP increased significantly when PEEP level was
      elevated in the study group. When PEEP was 0, 5 and 10 cm H(2)O, the CVP was
      (1.3+/-0.9), (3.1+/-1.3) and (4.5+/-1.3) mm Hg, respectively (1 mm Hg=0.133 kPa,
      all P<0.01). Whereas, in the control group, the changes in CVP was small. At 0, 5
      and 10 cm H(2)O PEEP levels, CVP was (6.9+/-1.3), (7.2+/-1.2) and (8.0+/-1.5) mm
      Hg, respectively, but when CVP at PEEP0 and PEEP5 was compared with that of
      PEEP10, the difference was significant (P<0.01 and P<0.05). There was slight
      increase of CIVP in both groups when PEEP was elevated. D(c-i)VP was increased
      significantly in the study group compared with control group (all P<0.01). But
      the value was gradually decreased when with elevation of PEEP. When PEEP level
      was elevated from 0 to 10 cm H(2)O, D(c-i)VP value was lowered from (4.9+/-1.7)
      mm Hg to (2.8+/-1.4) mm Hg. No significant difference in D(c-i)VP was found in
      the control group. The D(c-i)VP values in the control group were equal or lower
      than 1.5 mm Hg at three PEEP levels. (2)No relationship was found between CVP and
      CIVP at each PEEP level in the study group (r(1)=0.236, r(2)=0.299, r(3)=0.262,
      all P>0.05), but there was a statistically significant correlation between CVP
      and CIVP in the control group (r(1)=0.485, r(2)=0.679, r(3)=0.748, all P<0.05).
      CONCLUSION: The findings suggest that it may not be appropriate to use CVP or
      CIVP to evaluate the patients' blood volume and effect of volume resuscitation in
      the hypovolemic patients undergoing mechanical ventilation in combination with
      PEEP.

PMID- 19846002
TI  - [A clinical observation of airway mucosal injury as a result of mechanical
      ventilation for different duration].
AB  - OBJECTIVE: To observe the pathological changes in exfoliated cells from lower
      respiratory tract mucosa in patients undergoing mechanical ventilation for
      various duration. METHODS: The secretion of lower respiratory tract was collected
      in 144 patients of cerebral vascular diseases undergoing invasive mechanical
      ventilation, and exfoliated cells were examined under microscope at different
      time points. According to specimen collection time they were divided into five
      groups: less than 8 hours (28 cases), 8-24 hours (46 cases), 24 hours-3 days (22
      cases), 3-7 days (20 cases), 7-28 days (14 cases), and over 28 days (14 cases).
      Then the injury to airway mucosa at different time of mechanical ventilation was
      determined. RESULTS: The mucosal injury of trachea and bronchial was worsened
      gradually with the prolongation of mechanical ventilation. Airway mucosa
      structure of less than 8-hour of mechanical ventilation was generally normal,
      while most cells after 8-24 hours and 24 hours-3 days of ventilation showed mild
      injury, and most cells from tracheal and bronchial mucosa showed severe injury
      after 3-7 days, 7-28 days and over 28 days of ventilation. Except the difference
      was not statistically significant between 7-28 days and over 28 days group
      (P>0.05), the differences between remaining groups were statistically significant
      (all P<0.05). The correlated coefficient between the duration of mechanical
      ventilation and airway mucosal injury was 0.781 (P<0.05), and the difference was
      statistically significant. CONCLUSION: There are linear correlation between
      length of mechanical ventilation and the airway mucosal cell injury; injuries
      emerges when the mechanical ventilation time exceeds 8 hours with the
      prolongation mechanical ventilation time, there is severe damage of airway mucosa
      when mechanical ventilation lasted more than 7 days, but there is no difference
      in extent of injury after 7 days.

PMID- 19846003
TI  - [Clinical analysis of value of different modes of respiratory support in the
      treatment of critical patients].
AB  - OBJECTIVE: To investigate the relationship between the successful results with
      different methods and time of initiation of respiratory support in critically ill
      patients. METHODS: The clinical data of 458 critical care patients were reviewed
      and analyzed. Among the patients, there were 47 cases of cardio-pulmonary
      resuscitation, 105 cases of acute airway obstruction, 156 cases of acute
      respiratory failure, and 150 cases of chronic respiratory failure. Intubation, or
      tracheostomy, or non-invasive positive pressure ventilation (NPPV) at different
      times and occasions were performed in the patients. RESULTS: One hundred and
      seventeen cases (25.5%) died during the respiratory support treatment, 49 cases
      gave up the treatment, and 292 patients (63.8%) were cured after mechanical
      ventilation. As the success rate was the lowest in patients who survived cardio
      pulmonary resuscitation (21.3%, 10/47), it was higher in acute respiratory
      failure (55.1%, 86/156), and the best result (82.8%, 87/105) was obtained in the
      acute airway obstruction group and patients with chronic respiratory failure
      (72.7%, 109/150). In the group of patients undergoing early respiratory support,
      the cure rate was 95.0% (57/60) in patients with invasive method, and 95.5%
      (21/22) in the NPPV group. The result was significantly different compared with
      that of later treatment group [81.7% (68/82) in invasive group, and 60.9% (2/29)
      in NPPV group, both P<0.01]. It demonstrated that the earlier the respiratory
      support was given the better results. If the respiratory support was delayed,
      cure rate was significantly reduced [65.6% (63/96) in invasive group and 48.1%
      (13/27) in NPPV group, both P<0.01]. The cure rate was no difference between
      different modes of respiratory support between early treatment groups, however,
      invasive respiratory support was much better than NPPV [44.4% (40/90) and 0
      (0/5)] when instituted in the late stages (all P<0.01). CONCLUSION: It is of
      prime importance to ensure optimal ventilation in the early stage of diseases,
      the difficulty and risk of establishment of a patent airway are main problems in
      the treatment of critically ill patients.

PMID- 19846004
TI  - [Study on the effect of control mode of pressure and volume on cardiac index and
      intrathoracic blood volume index in critically ill patients].
AB  - OBJECTIVE: To compare the effect of control mode of pressure and volume of
      mechanical ventilation on cardiac index (CI), intrathoracic blood volume index
      (ITBVI) in patients. METHODS: Twenty-four patients in whom mechanical ventilation
      and pulse indicator continuous cardiac output (PiCCO) monitoring were necessary
      were involved, and they were divided into normal heart function group (9 cases)
      and heart dysfunction group (15 cases) on the base of CI. Mechanical ventilation
      was used with the mode of bi-level positive airway passage (BIPAP), and the
      inspiratory pressure was maintained at the tidal volume (V(T)) of 6, 10, 15
      ml/kg. After the mechanical ventilation mode was changed to synchronized
      intermittent mandatory ventilation (SIMV) and maintained for 20 minutes,
      breathing mechanics and central venous pressure (CVP), CI, ITBVI were measured.
      RESULTS: In the normal heart function group, there were decrease in mean arterial
      pressure (MAP), CI and ITBVI, increase in heart rate (HR), mean airway pressure
      (Pmean) and intrinsic positive end expiratory pressure (PEEPi) in both modes of
      mechanical ventilation without significant difference (P values were 0.067,
      0.124, 0.348, 0.328, 0.110, 0.187, respectively). Systemic vascular resistance
      index (SVRI) was higher in the BIPAP group compared with SIMV group (P=0.030). In
      the heart dysfunction group, the CI and ITBVI were decreased in the SIMV mode,
      and CI was decreased significantly in the 10 ml/kg group (P<0.05). Pmean in BIPAP
      group was increased than that in SIMV group in all V(T) levels (P values were
      0.003, 0.000, 0.004, respectively). There was no significant difference in SVRI,
      HR, MAP and PEEPi in all groups. CONCLUSION: In the two mechanical ventilation
      modes, with an increase in V(T), CI and ITBVI may decrease. The Pmean is lower
      when BIPAP mode in used compared with SIMV, when V(T) is same. So mechanical
      ventilation and V(T) can influence the readings of CI and ITBVI when PiCCO
      monitoring is employed.

PMID- 19846005
TI  - [Effect of mitogen-activated protein kinase kinase 6-p38 alpha signal pathway on
      receptor for advanced glycation end-product expression in alveolar epithelial
      cells induced by mechanical stretch].
AB  - OBJECTIVE: To investigate the role of mitogen-activated protein kinase kinase 6
      (MKK6) p38 alpha in mechanical stretch induced receptor for advanced glycation
      end-product (RAGE) expression in alveolar epithelial cells (A549). METHODS:
      Recombinant plasmids were transfected into A549 cells with liposome DOTAP. A549
      cells transfected with p38 alpha (AF)/pGFP and MKK6b (E)/pGFP plasmids were taken
      as treated groups, while the groups that transfected with pcDNA3 plasmid and pGFP
      plasmid served as blank transfection group and control group, respectively. All
      the groups were then cultured in 6-well Bioflex cell culture plates and exposed
      to cyclic mechanical stretch at 20% elongation. The infection and expression of
      gene were assessed by Western blotting analysis. The activity of p38 kinase in
      A549 cells and the expression of RAGE protein and mRNA were observed. RESULTS:
      The transfection of MKK6b (E) led to a markedly increase in p38 kinase activity
      compared with control group. In contrast, the transfection of p38 alpha (AF)
      significantly inhibited p38 kinase activity. Compared with control group, stretch
      markedly increased RAGE protein and mRNA expression in MKK6b (E) transfected
      cells, while it markedly decreased RAGE expression in p38 alpha (AF) transfected
      cells. CONCLUSION: MKK6 p38 alpha signaling pathway regulates the expression of
      RAGE induced by mechanical stretch in A549 cells.

PMID- 19846006
TI  - [Influence of the venous catheter site on data of pulse indicator continuous
      cardiac output monitoring].
AB  - OBJECTIVE: To compare the use of subclavian vein catheter and femoral vein
      catheter, in monitoring pulse indicator continuous cardiac output (PiCCO)
      monitoring data cardiac index (CI), extravascular lung water index (EVLWI), and
      global end-diastolic volume index (GEDVI) with central venous injection of the
      bolus cold saline injection, in order to determine whether the femoral vein
      access, which is not typically used, could be used to obtain reliable data.
      METHODS: Thirteen patients in Beijing Hospital intensive care unit (ICU) were
      involved, from January 2007 to March 2009. Each patient was monitored with
      PiCCOplus device, after an injection of cold saline bolus via both femoral and
      subclavian venous catheter. Paired t-test and Bland-Altman analysis were used to
      compare CI, EVLWI and GEDVI values. RESULTS: Data of 39 measurements were
      collected. The bias between femoral injection and subclavian injection were CI
      (0.28+/-0.46) L x min(-1) x m(-2), EVLWI (1.05+/-1.89) ml/kg, GEDVI (195.2+/
      105.7) ml/m(2), and they were statistically significant (P values was 0.000 5,
      0.001 3, <0.0001, respectively). The Bland-Altman analysis showed an clinically
      overestimation of GEDVI after femoral injection (limit of concordance was -11.9,
      402.3), compared with that after subclavian injection. CONCLUSION: Measurements
      with a cold saline bolus via a femoral catheter, compared to those via a
      subclavian catheter, lead to overestimation of CI, EVLWI and GEDVI values, and a
      great bias of GEDVI should be taken into account in clinical work.

PMID- 19846007
TI  - [A study on the effect of recruitment maneuver imposed on extravascular lung
      water in patients with acute respiratory distress syndrome].
AB  - OBJECTIVE: To investigate the possible effects of recruitment maneuver (RM)
      imposing on extravascular lung water (EVLW) in patients with acute respiratory
      distress syndrome (ARDS). METHODS: Twenty patients with ARDS who were eligible
      for the study were randomized to two groups, one group of which received regular
      therapy+RM (RM group), and to the other group only regular therapy was given
      (control group). Mechanical ventilation of all the patients was performed on the
      principles of lung protective ventilation. RM was carried out in bi-level
      positive airway passage (BIPAP) mode, and repeated every 8 hours per day until on
      the 7th day or before weaning of mechanical ventilation. The treatment was same
      between the two groups except RM. Baseline data and the influencing factors of
      EVLW were all recorded, which included everyday EVLW, extravascular lung water
      index (EVLWI) after RM, respiratory mechanics, oxygenation parameters, central
      venous pressure (CVP), plasma colloid osmotic pressure (COP), dosage of
      corticosteroid and adrenergic drugs, 24-hour net fluid balance. RESULTS: EVLW and
      EVLWI in RM and control group showed a tendency of decrease with passage of time,
      but the difference between both groups had no statistical significance (all
      P>0.05). The comparisons between the influencing factors of the groups,
      consisting of CVP, COP, noradrenaline and hydrocortisone, had no significant
      difference either (all P>0.05). Dopamine dosage in RM group on the 4th day was
      smaller than that of control group (P<0.05). Net fluid balance in RM group on the
      7th day was negative, whereas it was positive in control group (P<0.05). Mean
      airway pressure [Pmean, RM group (18.8+/-3.2) cm H(2)O (1 cm H(2)O=0.098 kPa) vs.
      control group (16.6+/-3.9) cm H(2)O] and lung quasi-static compliance [Cstat, RM
      group (36.5+/-14.5) ml/cm H(2)O vs. control group (29.3+/-12.0) ml/cm H(2)O] in
      RM group were higher than those in control group (both P<0.05). Cstat on the 5th
      day was higher than that on the 2nd and 3rd day in RM group (both P<0.05). But
      oxygenation index (PaO(2)/FiO(2)) showed no distinct difference between the
      groups (all P>0.05). CONCLUSION: RM for the patients with ARDS can merely improve
      lung mechanics without obvious effect on EVLW. Neither of the influencing factors
      involved in the study has impact on emergence and clearance of EVLW.

PMID- 19846008
TI  - [Clinical effects of low-stretch ventilation on acute respiratory distress
      syndrome].
AB  - OBJECTIVE: To investigate the effectiveness of low-stretch as compared with low
      tidal-volume strategy in the treatment of acute respiratory distress syndrome
      (ARDS). METHODS: Eighty-five cases of ARDS patients were randomly divided into
      low-stretch group (42 cases) and low-tidal-volume group (43 cases). The former
      group of patient received pressure assist control mode with not higher than 35 cm
      H(2)O (1 cm H(2)O=0.098 kPa) of peak pressure or pressure support mode
      ventilation with not higher than 30 cm H(2)O of Pplateau, while in low-tidal
      volume group tidal volume of no more than 6 ml/kg of predicted body weight was
      given. The mortality rate within 28 days, the incidence of hypercapnia, the
      duration of using sedatives and neuromuscular blockade agents, the time of
      ventilation and the length of intensive care unit (ICU) stay were compared
      between two groups. According to the monitored expiratory tidal volume (V(T)e),
      the low-stretch group was divided into low-tidal-volume subgroup (V(T)e < or =6
      ml/kg, 11 cases) and non-low-tidal-volume subgroup (V(T)e >6 ml/kg, 31 cases).
      The mortality within 28 days and the incidence of hypercapnia were compared
      between two subgroups. RESULTS: There was no significant difference in the 28-day
      mortality rate between two groups (34.0% vs. 37.0%, P>0.05), but patients of low
      stretch group had lower incidence of hypercapnia than low-tidal-volume group
      (10.6% vs. 40.7%, P<0.05), and also the duration of using sedatives [(4.5+/-1.2)
      days vs. (8.7+/-2.3) days] and neuromuscular blockade agents [(8.4+/-2.1) days
      vs. (10.7+/-1.2) days], and the length of ventilation and ICU stay [(10.2+/-2.2)
      days vs. (13.7+/-3.1) days, all P<0.05] were less. Low tidal volume occurred in
      26.2% of low-stretch group, and the low-tidal-volume subgroup had higher 28-day
      mortality rate (40.8%) and incidence of hypercapnia (65.7%) than non-low-tidal
      volume subgroup (13.2% and 8.6%, both P<0.05). CONCLUSION: Compared with low
      tidal-volume strategy, low-stretch strategy can reduce the incidence of
      hypercapnia, the length of ventilation and ICU stay for ARDS patients, but have
      similar mortality rate. When low-stretch strategy is exercised, an inappropriate
      low tidal volume may be associated with poor outcome of ARDS.

PMID- 19846009
TI  - [Non-invasive positive pressure ventilation in patients with acute respiratory
      distress syndrome: a prospective cohort study].
AB  - OBJECTIVE: To investigate the efficiency of the application of non-invasive
      positive pressure ventilation (NPPV) as a first-line intervention in patients
      with acute respiratory distress syndrome (ARDS). METHODS: A prospective cohort
      study was designed to analyze the clinical data of patients with ARDS in
      respiratory intensive care unit (RICU) of Beijing Chaoyang Hospital admitted
      between January 2004 and December 2007. RESULTS: (1)31 patients, age (49+/-17)
      years, with acute physiology and chronic health evaluation II (APACHEII) score of
      14+/-8 and oxygenation index (PaO(2)/FiO(2) of (123+/-32) mm Hg (1 mm Hg=0.133
      kPa), were enrolled in the study. There were 23 males and 8 females. (2)The
      successful rate of NPPV was 74.2% (23/31) and it was significantly higher in
      patients without pulmonary infection than that in patients with pulmonary
      infection (100% vs. 60%, P=0.017). (3)In the successful group, heart rate (HR),
      respiratory rate (RR) and PaO(2)/FiO(2) were improved significantly at the time
      of 2 hours and 24 hours of NPPV compared with NPPV before (all P<0.01), while
      there was no significant improvement observed in the failure group. Furthermore,
      an increase in arterial partial pressure of carbon dioxide (PaCO(2)) was observed
      in the latter (P<0.05). No serious complications were seen in association with
      NPPV in all recruited patients. CONCLUSION: NPPV may be the first-line
      intervention for a selected group of ARDS patients, while invasive ventilation
      should be considered for those patients with high risk of NPPV failure as
      indicated by worsening of vital signs and arterial blood gas analysis after a
      short time of using NPPV, and also in cases where pulmonary infection is the
      underlying disease of ARDS.

PMID- 19846010
TI  - [Clinical experience of spontaneous breathing trial in weaning mechanical
      ventilation].
AB  - OBJECTIVE: To compare the spontaneous breathing trial (SBT) weaning mode with the
      classical weaning mode for extubation in patients undergoing mechanical
      ventilation. METHODS: Fifty-seven patients showing stabilized condition after
      mechanical ventilation, were divided into two groups. In 21 patients, admitted
      from June 2004 to December 2005, a gradual decrease in respiratory support as the
      mode of weaning of mechanical ventilation. In 36 patients, admitted from January
      2006 to March 2007, SBT weaning mode was adopted. The length of mechanical
      ventilation and stay in intensive care unit (ICU), ventilator-associated
      pneumonia (VAP) rate, retubing rate in 48 hours, ICU mortality were compared
      between two groups. RESULTS: The length of mechanical ventilation were (59.4+/
      37.1) hours and (111.4+/-59.8) hours (P=0.001), length of stay in ICU were (8.0+/
      5.5) days and (15.3+/-14.3) days (P=0.034), VAP rate was 16.7% and 38.0%
      (P=0.070), retubing rate in 48 hours were 19.4% and 5.0% (P=0.253), ICU mortality
      rate was 25.0% and 24.0% (P=0.920) in SBT group and control group, respectively.
      CONCLUSION: The SBT weaning mode shortens the time of mechanical ventilation and
      the ICU stay days. Both groups have the identical VAP rate, retubing rate in 48
      hours, and ICU mortality.

PMID- 19846012
TI  - [Comparison between percutaneous dilatational tracheostomy and surgical
      conventional tracheostomy in clinical practice].
AB  - OBJECTIVE: To discuss the difference between surgical conventional tracheostomy
      (SCT) and percutaneous dilatational tracheostomy (PDT). METHODS: Thirty cases
      with SCT and 30 cases with PDT were selected, in whom the operation time, amount
      of blood loss, size of operative incision, incision healing time, infection rate,
      incidence rate of subcutaneous emphysema, incidence of mediastinal emphysema,
      incidence rate of hypoxemia, and incidence rate of tracheo-esophageal fistula
      were observed. RESULTS: The operation time was significantly shortened [(12.75+/
      4.42) minutes vs. (29.60+/-8.14) minutes], blood loss was significantly decreased
      [(12.23+/-10.10) ml vs. (26.10+/-13.31) ml], size of operation incision was
      significantly shorter [(1.48+/-0.12) cm vs. (3.98+/-0.38) cm], incision healing
      time was significantly shorter [(2.0+/-1.0) days vs. (5.0+/-2.0) days] in PDT
      compared with SCT (all P<0.05). PDT had less subcutaneous emphysema, infection
      and mediastinal emphysema in PDT than those in SCT (all P<0.05). CONCLUSION: PDT
      is easier in performance, with less blood loss, shorter operation time, incision
      healing time and size of operation incision, lower infection rate, lower
      incidence of subcutaneous emphysema and mediastinal emphysema than SCT.

PMID- 19846014
TI  - [The design and use of a mobile intensive care unit ambulance].
AB  - OBJECTIVE: To improve the range of use and efficiency of first-aid in a disaster,
      a mobile intensive care unit (ICU) ambulance was designed and evaluated. METHODS:
      The data of disasters, accidental injury in astronauts, injuries occurred in
      conflicts in foreign nations were reviewed and analyzed, together with our
      clinical experience of first-aid, a mobile ICU in an ambulance was designed.
      RESULTS: Provided with automatic cardiopulmonary resuscitation apparatus and
      instruments for surgical life-saving operation, the mobile ICU ambulance could
      allow the occupants to perform effective rescue means during rush hour of urban
      traffic. The new model of ambulance was proved to be able to afford an increased
      rescue rate in disaster scenario. CONCLUSION: The disability rate and fatality of
      accidental injuries and local conflicts could be reduced significantly by the use
      of our mobile ICU ambulance.

PMID- 19846015
TI  - [Comparison of different modes of weaning mechanical ventilation].

PMID- 19846016
TI  - [Management of unilateral acute respiratory distress syndrome with mechanical
      ventilation].

PMID- 19846017
TI  - [The influence of early tracheostomy on the prognosis of lung infection after
      thoracic operation].

PMID- 19846018
TI  - [Clinical analysis of the effect of non-invasive mechanical ventilation in 519
      cases of respiratory failure].

PMID- 19846020
TI  - [Advances in the study of volume management monitoring indexes].

PMID- 19846021
TI  - [Emerging role of angiopoietin 2 in sepsis and acute lung injury/acute
      respiratory distress syndrome].

PMID- 19846022
TI  - Lapatinib for the treatment of HER2-overexpressing breast cancer.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical effectiveness and cost-effectiveness of lapatinib for the treatment of
      advanced or metastatic HER2-overexpressing breast cancer based upon a review of
      the manufacturer's submission to the National Institute for Health and Clinical
      Excellence (NICE) as part of the single technology appraisal (STA) process. The
      scope included women with advanced, metastatic or recurrent HER2-overexpressing
      breast cancer who have had previous therapy that includes trastuzumab. Outcomes
      were time to progression, progression-free survival, response rates, overall
      survival, health-related quality of life and adverse effects. The submission's
      evidence came from one randomised controlled trial (RCT) of reasonable
      methodological quality, although it was not powered to detect a statistically
      significant difference in mean overall survival. Median time to progression was
      longer in the lapatinib plus capecitabine arm than in the capecitabine
      monotherapy arm {27.1 [95% confidence interval (CI) 17.4 to 49.4] versus 18.6
      [95% CI 9.1 to 36.9] weeks; hazard ratio 0.57 [95% CI 0.43 to 0.77; p =
      0.00013]}. Median overall survival was very similar between the groups [67.7 (95%
      CI 58.9 to 91.6) versus 66.6 (95% CI 49.1 to 75.0) weeks; hazard ratio 0.78 (95%
      CI 0.55 to 1.12; p = 0.177)]. Median progression-free survival was statistically
      significantly longer in the lapatinib plus capecitabine group than in the
      capecitabine monotherapy group [27.1 (95% CI 24.1 to 36.9) versus 17.6 (95% CI
      13.3 to 20.1) weeks; hazard ratio 0.55 (95% CI 0.41 to 0.74); p = 0.000033]. The
      manufacturer's economic model to estimate progression-free and overall survival
      for patients with HER2-positive advanced/metastatic breast cancer who had
      relapsed following treatment with an anthracycline, a taxane and trastuzumab was
      appropriate for the disease area. The base-case incremental cost-effectiveness
      ratios (ICERs) for lapatinib plus capecitabine compared with capecitabine
      monotherapy or vinorelbine monotherapy were higher than would conventionally be
      considered cost-effective. When compared with trastuzumab-containing regimes,
      lapatinib plus capecitabine dominated. In sensitivity analyses the ICER for
      lapatinib plus capecitabine compared with capecitabine monotherapy or vinorelbine
      monotherapy was robust to variation in assumptions. In all sensitivity analyses
      the ICERs remained higher than would conventionally be considered cost-effective.
      ICERs for trastuzumab-containing regimes were particularly sensitive to
      assumptions over the frequency of treatment, which had a large effect on the cost
      effectiveness of lapatinib plus capecitabine. In conclusion, there was a general
      lack of evidence on the effectiveness of comparators included in the model and on
      key parameters such as dose adjustments and the model outputs need to be
      interpreted in the light of this uncertainty. At the time of writing, NICE were
      still considering the available evidence for this appraisal.

PMID- 19846023
TI  - Infliximab for the treatment of ulcerative colitis.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical effectiveness and cost-effectiveness of infliximab for moderately to
      severely active ulcerative colitis (UC) based upon a review of the manufacturer's
      submission to the National Institute for Health and Clinical Excellent (NICE) as
      part of the single technology appraisal (STA) process. The submission indicated
      that the efficacy of infliximab (5 mg/kg) had been demonstrated in terms of
      higher response rates and a sustained response in health-related quality of life.
      For the cost-effectiveness analysis, the manufacturer built a Markov model to
      compare infliximab with standard care. It estimated the incremental cost per
      quality-adjusted life-year (QALY) gained was between 25,044 pounds and 33,866
      pounds depending on the strategy used. The ERG report generally agreed with the
      evidence on effectiveness of infliximab for subacute exacerbations of UC.
      However, there were several areas of uncertainty, of which the interpretation of
      the importance of the quality of life changes in the subacute situation and the
      assessment of the adequacy of the evidence of effectiveness of infliximab in the
      acute hospital-based situation were considered pre-eminent by the ERG. This
      challenged the estimates of cost-effectiveness offered and suggested that there
      should be a separate assessment of infliximab for acute exacerbations of
      moderately to severely active UC. The summary of the NICE guidance issued in
      April 2008 as a result of the STA states that: infliximab is not recommended for
      the treatment of subacute manifestations of moderately to severely active UC.

PMID- 19846024
TI  - Rimonabant for the treatment of overweight and obese people.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical and cost-effectiveness of rimonabant for the treatment of obese or
      overweight patients based upon a review of the manufacturer's submission to the
      National Centre for Health and Clinical Excellence (NICE) as part of the single
      technology appraisal (STA) process. The submission's main evidence came from four
      randomised controlled trials. Rimonabant resulted in a significantly greater
      benefit than placebo for all primary weight loss outcomes. At 1 year, rimonabant
      had a statistically significant beneficial effect on systolic blood pressure,
      high-density lipoprotein cholesterol, triglycerides and fasting plasma glucose in
      diabetics and non-diabetics, and glycosylated haemoglobin in diabetics.
      Improvements were maintained over 2 years with rimonabant; withdrawal of
      rimonabant at 1 year resulted in a reduction in weight loss until there was no
      difference from placebo at 2 years. Psychiatric adverse events were experienced
      by 26% and 14% of rimonabant and placebo patients respectively; figures for
      symptoms of depression were 9% and 5% respectively. Pairwise comparisons of
      orlistat, sibutramine and rimonabant showed beneficial effects of rimonabant over
      orlistat and sibutramine for weight loss outcomes; however, response hurdles
      imposed on orlistat or sibutramine in clinical practice may not have been applied
      in the orlistat and sibutramine trials. The manufacturer's Markov cohort model
      evaluated rimonabant versus orlistat, sibutramine and diet and exercise alone for
      three base-case populations. The incremental cost-effectiveness ratio (ICER) of
      rimonabant varied from 10,534 pounds to 13,236 pounds per quality-adjusted life
      year (QALY) versus diet and exercise, to 8977 pounds to 12,138 pounds per QALY
      versus orlistat, to 1463 pounds to 3908 pounds per QALY versus sibutramine. In
      subgroup analysis there was a wider variation in the ICER estimates although none
      exceeded 20,000 pounds per QALY. The ICER of rimonabant remained under 20,000
      pounds per QALY in reanalyses by the manufacturer and the ERG, with the results
      sensitive to the source of health-related quality of life (HRQoL) benefits in the
      model. Four treatment strategies were modelled in comparisons of rimonabant
      versus diet and exercise alone and orlistat and sibutramine in which rimonabant
      was continued only in patients achieving 5% weight loss at 3, 6, 9 or 12 months.
      In pairwise comparisons rimonabant remained below a threshold of 30,000 pounds
      per QALY in 70% of the comparisons reported. The results were most sensitive to
      the decrement applied to depression and the costs of screening for depression. In
      conclusion, areas of uncertainty remain in relation to the clinical effectiveness
      and cost-effectiveness of rimonabant, for example lack of evidence on long-term
      outcomes and the effect of rimonabant on cardiovascular events, developing
      diabetes and mortality, and lack of data on the HRQoL benefits associated with
      rimonabant. The lack of response hurdles applied to sibutramine and orlistat
      means that the comparator strategies were not considered by the ERG to reflect
      their respective product licenses or current NHS use. The NICE guidance issued as
      a result of the STA states that rimonabant is recommended as an adjunct to diet
      and exercise for adults who are obese or overweight and who have had an
      inadequate response to, are intolerant of or are contraindicated to orlistat and
      sibutramine.

PMID- 19846025
TI  - Telbivudine for the treatment of chronic hepatitis B infection.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical effectiveness and cost-effectiveness of telbivudine for the treatment of
      chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's
      submission to the National Institute for Health and Clinical Excellence (NICE) as
      part of the single technology appraisal (STA) process. The submission's evidence
      came from one randomised controlled trial (RCT) (GLOBE) of reasonable
      methodological quality comparing telbivudine with lamivudine. One other RCT that
      appeared to meet the inclusion criteria was excluded from the submission. For the
      primary outcome of therapeutic response telbivudine was statistically superior to
      lamivudine at weeks 52 and 104 for hepatitis B e antigen (HBeAg)-positive
      patients, and at week 104 for HBeAg-negative patients. There were statistically
      significant differences in favour of telbivudine for some secondary outcomes at 2
      years including hepatitis B virus (HBV) DNA reduction, HBV DNA non-detectability
      and alanine aminotransferase normalisation though not for HBeAg-positive
      patients. In HBeAg-positive patients there was no significant difference between
      treatment groups for HBeAg loss or seroconversion at any time point. The
      incidence of adverse events was similar between treatments. Two RCTs comparing
      entecavir with lamivudine were included in the indirect comparison; however, this
      was poorly conducted and the results should be treated with caution. The
      manufacturer developed two economic models to determine the cost-effectiveness of
      telbivudine. Evidence on the efficacy of telbivudine and lamivudine was taken
      from the GLOBE trial; efficacy of adefovir was based on assumption. There was a
      lack of critical assessment and assurance of the quality of the data used to
      populate the models. The manufacturer concluded that telbivudine is a cost
      effective option compared with lamivudine using evidence from the viral load
      model [HBeAg-positive patients/HBeAg-negative patients: mean incremental cost
      19,087 pounds/49,003 pounds, mean quality-adjusted life-year (QALY) gain
      1.30/4.67, incremental cost-effectiveness ratio (ICER) 14,665 pounds/10,497
      pounds per QALY]. Resubmitted results after a request for clarification by the
      ERG gave less favourable ICERs (HBeAg-positive patients/HBeAg-negative patients:
      mean incremental cost 23,983 pounds/41,910 pounds, mean QALY gain 1.56/2.07, ICER
      15,377 pounds/20,256 pounds per QALY). The manufacturer concluded that
      telbivudine is a cost-effective option (on its own or followed by adefovir) for
      patients who have developed resistance to first-line telbivudine treatment;
      however, the presentation of the results was not ideal. In conclusion, although
      telbivudine was statistically superior to lamivudine for most antiviral outcomes,
      the difference was not clinically significant; in addition, the cost
      effectiveness evidence for telbivudine presented in the manufacturer's submission
      was limited. The NICE guidance issued as a result of the STA states that
      telbivudine is not recommended for the treatment of chronic hepatitis B and that
      people currently receiving telbivudine should have the option to continue therapy
      until they and their clinicians consider it appropriate to stop.

PMID- 19846026
TI  - Entecavir for the treatment of chronic hepatitis B infection.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical and cost-effectiveness of entecavir for the treatment of chronic
      hepatitis B (CHB) in adults based upon a review of the manufacturer's submission
      to the National Institute for Health and Clinical Excellence (NICE) as part of
      the single technology appraisal (STA) process. The submission's evidence came
      from five randomised controlled trials (RCTs), of good methodological quality and
      measuring a range of clinically relevant outcomes, comparing entecavir with
      lamivudine. After 1 year of treatment entecavir was statistically superior to
      lamivudine in terms of the proportion of patients achieving hepatitis B virus
      (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and
      histological improvement, but not in terms of the proportion of patients
      achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse
      or serious adverse events was similar for both treatments. The results of the
      manufacturer's mixed treatment comparison (MTC) model to compare entecavir with
      the comparator drugs in nucleoside-naive patients were considered to be uncertain
      because of concerns over its conduct and reporting. For the economic evaluation
      the manufacturer constructed two Markov state transition models, one in HBeAg
      positive and one in HBeAg-negative patients. The modelling approach was
      considered reasonable subject to some uncertainties and concerns over some of the
      structural assumptions. In HBeAg-positive patients the base-case incremental cost
      effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated
      interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life
      year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg
      negative patients the base-case ICERs for entecavir compared with lamivudine,
      pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and
      6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory
      patients entecavir dominated adefovir added to lamivudine. In one-way
      deterministic sensitivity analysis on all key input parameters for entecavir
      compared with lamivudine in nucleoside-naive patients, ICERs generally remained
      under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside
      naive HBeAg-positive patients the probability of the ICER for entecavir being
      below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine,
      pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive
      HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively.
      The manufacturer's lifetime treatment scenario for HBeAg-negative patients and
      the ERG's 20-year treatment scenario for HBeAg-positive patients increased the
      ICERs, particularly in the latter case. Amending the HBeAg-negative model so that
      patients with compensated cirrhosis would also receive lifetime treatment gave
      probabilities of entecavir being cost-effective at a willingness to pay of 20,000
      pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in
      August 2008 as a result of the STA states that entecavir is recommended as an
      option for the treatment of people with chronic HBeAg-positive or HBeAg-negative
      hepatitis B in whom antiviral treatment is indicated.

PMID- 19846027
TI  - Febuxostat for the treatment of hyperuricaemia in people with gout: a single
      technology appraisal.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical effectiveness and cost-effectiveness of febuxostat for the management of
      hyperuricaemia in patients with gout based upon a review of the manufacturer's
      submission to the National Institute for Health and Clinical Excellence (NICE) as
      part of the single technology appraisal (STA) process. The submission's evidence
      came from two randomised controlled trials comparing the efficacy and safety of
      febuxostat with allopurinol. The trials were of reasonable methodological quality
      and measured a clinically relevant range of outcomes. A pooled clinical efficacy
      analysis showed that a daily dose of 80 mg or 120 mg of febuxostat was
      significantly more effective than fixed-dose allopurinol (300/100 mg/day) at
      lowering serum uric acid (sUA) levels to therapeutic targets (< 6 mg/dl);
      however, a large percentage of febuxostat patients did not achieve the primary
      end point and the fixed-dose allopurinol regimen may have introduced bias. There
      were no differences between treatments in more clinically important outcomes such
      as gout flares and tophi resolution after 52 weeks of treatment. No subgroup
      analyses were conducted for patients with renal impairment, non-responders to
      allopurinol or patients with severe disease. Supplementary data from a 2-year
      open-label extension study were also provided, but were difficult to interpret
      and poorly reported. The incidence of adverse events was similar between
      treatments, although more febuxostat recipients discontinued treatment
      prematurely. A decision tree model was developed to determine the cost
      effectiveness of febuxostat. The scope was limited to the comparison of continual
      febuxostat treatment with continual allopurinol treatment. Switching between
      treatments or withdrawing treatment in patients whose sUA levels had not
      decreased was not permitted. The model predicted a cost-effectiveness of 16,324
      pounds [95% confidence interval (CI) 6281 pounds to 239,928 pounds] per quality
      adjusted life-year (QALY) gained for febuxostat compared with allopurinol after 2
      years of treatment. The incremental cost per QALY was below 20,000 pounds in 63%
      of the simulations undertaken. Changes in the time horizon did not materially
      affect the results. The ERG believes that the modelling structure employed was
      not appropriate to estimate the cost-effectiveness of febuxostat within a
      treatment algorithm. In addition, there were concerns about the methodology used
      for collecting data on key model inputs. Given these reservations the cost
      effectiveness of febuxostat could not be determined. The guidance issued by NICE
      in August 2008 as a result of the STA states that febuxostat is recommended as an
      option for the management of chronic hyperuricaemia in gout only for people who
      are intolerant of allopurinol or for whom allopurinol is contraindicated.

PMID- 19846028
TI  - Rivaroxaban for the prevention of venous thromboembolism: a single technology
      appraisal.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical effectiveness and cost-effectiveness of rivaroxaban for the prevention
      of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee
      replacement surgery based upon a review of the manufacturer's submission to the
      National Institute for Health and Clinical Excellence (NICE) as part of the
      single technology appraisal (STA) process. The submission's evidence came from
      four randomised controlled trials (RCTs) comparing rivaroxaban with enoxaparin
      [RECORD (Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous
      thrombosis and pulmonary embolism) 1-4] and three comparing dabigatran with
      enoxaparin [RE-NOVATE (the prevention of venous thromboembolism after total hip
      replacement trial), RE-MODEL (the prevention of venous thromboembolism after
      total knee replacement trial) and RE-MOBILIZE (the prevention of venous
      thromboembolism after total knee arthroplasty trial)]. The evidence from the four
      RECORD trials indicates that rivaroxaban had superior efficacy over enoxaparin
      after total hip replacement (THR) and total knee replacement (TKR). For the
      composite primary outcome of any deep vein thrombosis (DVT), non-fatal pulmonary
      embolism (PE) and death from all causes the relative risk reductions were 70-79%
      in THR and 31-49% in TKR. Rivaroxaban also had superior efficacy over enoxaparin
      for the secondary outcome major VTE. Rivaroxaban was not inferior to enoxaparin
      on the safety outcome of major bleeding. After the correction of some errors
      found by the ERG, the manufacturer's economic model represented a reasonable
      model of patients receiving prophylaxis for THR or TKR. In the base-case analyses
      rivaroxaban dominated both enoxaparin and dabigatran. The incremental costs saved
      and quality-adjusted life-years (QALYs) gained were small (below 200 pounds and
      0.005, respectively, per person). Analyses were conducted sampling from the
      distributions observed from the RCTs. When all parameters were sampled
      rivaroxaban dominated enoxaparin in all scenarios except for two, in which
      enoxaparin produced more QALYs than rivaroxaban and had an incremental cost per
      QALY gained of 5000 pounds and 8000 pounds respectively. Rivaroxaban dominated
      dabigatran when RECORD 1 and RECORD 2, individually or pooled, were compared with
      RE-NOVATE and when all four rivaroxaban RCTs pooled were compared with all three
      dabigatran RCTs. Dabigatran dominated rivaroxaban comparing RECORD 4 with RE
      MODEL and RE-MOBILIZE, and was more cost-effective than rivaroxaban comparing
      RECORD 3 (incremental cost per QALY gained of rivaroxaban compared with
      dabigatran of 123,000 pounds) or RECORD 3 and RECORD 4 pooled (incremental cost
      per QALY gained of dabigatran compared with rivaroxaban of 400 pounds) with RE
      MODEL and RE-MOBILIZE. In conclusion, the evidence indicates that rivaroxaban is
      not inferior to enoxaparin in terms of the primary and secondary outcomes. The
      submission presents a reasonable estimation of the cost-effectiveness of
      rivaroxaban compared with enoxaparin and dabigatran, although the uncertainty in
      the decision has been underestimated. The results are particularly sensitive to
      any assumed difference in the number of fatal PEs, but the ERG does not believe
      there is sufficient evidence to support a difference between interventions. The
      NICE guidance issued as a result of the STA states that: riveroxaban, within its
      marketing authorisation, is recommended as an option for the prevention of venous
      thromboembolism in adults having elective THR or elective TKB.

PMID- 19846029
TI  - Cetuximab for the treatment of recurrent and/or metastatic squamous cell
      carcinoma of the head and neck.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical effectiveness and cost-effectiveness of cetuximab for recurrent and/or
      metastatic squamous cell carcinoma of the head and neck (SCCHN) based upon a
      review of the manufacturer's submission to the National Institute for Health and
      Clinical Excellence (NICE) as part of the single technology appraisal (STA)
      process. The submission's evidence came from a single reasonably high-quality
      randomised controlled trial (RCT) [EXTREME (Erbitux in First-Line Treatment of
      Recurrent or Metastatic Head and Neck Cancer); n = 442] comparing cetuximab plus
      chemotherapy (CTX) with CTX alone. Cetuximab plus CTX had significant effects
      compared with CTX alone on the primary outcome of overall survival (10.1 versus
      7.4 months respectively) and the secondary outcomes of progression-free survival
      (PFS) (5.6 versus 3.3 months), best overall response to therapy (35.6% versus
      19.5%), disease control rate (81.1% versus 60%) and time-to-treatment failure
      (4.8 versus 3.0 months), but not on duration of response (5.6 months versus 4.7
      months). No safety issues with cetuximab arose beyond those already previously
      documented. The manufacturer developed a two-arm state-transition Markov model to
      evaluate the cost-effectiveness of cetuximab plus CTX versus CTX alone, using
      clinical data from the EXTREME trial. The ERG recalculated the base-case cost
      effectiveness results taking changes in parameters and assumptions into account.
      Subgroup and threshold analyses were also explored. The manufacturer reported an
      incremental cost-effectiveness ratio (ICER) of 121,367 pounds per quality
      adjusted life-year (QALY) gained and an incremental cost per life-year gained of
      92,226 pounds. Univariate sensitivity analysis showed that varying the cost of
      day-case infusion and the utility values in the stable/response health state of
      the cetuximab plus CTX arm had the greatest impact on the ICER. Probabilistic
      sensitivity analysis illustrated that cetuximab plus CTX is unlikely to be cost
      effective for patients with recurrent and/or metastatic SCCHN, even at what would
      usually be considered very high levels of willingness to pay for an additional
      QALY. With regard to the economic model the appropriateness and reliability of
      parametric survival projection beyond the duration of trial data could not be
      fully explored because of lack of information. The ERG also questioned the
      appropriateness of economic modelling in this STA as evidence is available only
      from a single RCT. In conclusion, the ERG considers that patients with metastatic
      SCCHN were not shown to receive a significant survival benefit from cetuximab
      plus CTX compared with CTX alone and that even setting a lower price for
      cetuximab would not strengthen the manufacturer's case for cost-effectiveness.

PMID- 19846031
TI  - Ustekinumab for the treatment of moderate to severe psoriasis.
AB  - This paper presents a summary of the evidence review group (ERG) report into the
      clinical effectiveness and cost-effectiveness of ustekinumab for the treatment of
      moderate to severe psoriasis based upon a review of the manufacturer's submission
      to the National Institute for Health and Clinical Excellence (NICE) as part of
      the single technology appraisal (STA) process. The submission's main evidence
      came from three randomised controlled trials (RCTs), of reasonable methodological
      quality and measuring a range of clinically relevant outcomes. Higher proportions
      of participants treated with ustekinumab (45 mg and 90 mg) than with placebo or
      etanercept achieved an improvement on the Psoriasis Area and Severity Index
      (PASI) of at least 75% (PASI 75) after 12 weeks. There were also statistically
      significant differences in favour of ustekinumab over placebo for PASI 50 and
      PASI 90 results, and for ustekinumab over etanercept for PASI 90 results. A
      weight-based subgroup dosing analysis for each trial was presented, but the
      methodology was poorly described and no statistical analysis to support the
      chosen weight threshold was presented. The manufacturer carried out a mixed
      treatment comparison (MTC); however, the appropriateness of some of the
      methodological aspects of the MTC is uncertain. The incidence of adverse events
      was similar between groups at 12 weeks and withdrawals due to adverse events were
      low and less frequent in the ustekinumab than in the placebo or etanercept
      groups; however, statistical comparisons were not reported. The manufacturer's
      economic model of treatments for psoriasis compared ustekinumab with other
      biological therapies. The model used a reasonable approach; however, it is not
      clear whether the clinical effectiveness estimates from the subgroup analysis,
      used in the base-case analysis, were methodologically appropriate. The base-case
      incremental cost-effectiveness ratio for ustekinumab versus supportive care was
      29,587 pounds per quality-adjusted life-year (QALY). In one-way sensitivity
      analysis the model was most sensitive to the number of hospital days associated
      with supportive care, the cost estimate for intermittent etanercept 25 mg and the
      utility scores used. In the ERG's scenario analysis the model was most sensitive
      to the price of ustekinumab 90 mg, the proportion of patients with baseline
      weight > 100 kg and the relative risk of intermittent versus continuous
      etanercept 25 mg. In the ERG's probabilistic sensitivity analysis ustekinumab had
      the highest probability of being cost-effective at conventional NICE thresholds,
      assuming the same price for the 45-mg and 90-mg doses; however, doubling the
      price of ustekinumab 90 mg resulted in ustekinumab no longer dominating the
      comparators. In conclusion, the clinical effectiveness and cost-effectiveness of
      ustekinumab in relation to other drugs in this class is uncertain. Provisional
      NICE guidance issued as a result of the STA states that ustekinumab is
      recommended as a treatment option for adults with plaque psoriasis when a number
      of criteria are met. Final guidance is anticipated in September 2009.

PMID- 19846032
TI  - Periprocedural management of anticoagulation and antiplatelet therapies in
      patients undergoing electrophysiologic procedures.
AB  - Electrophysiologic studies, radiofrequency ablation, and device implantations
      including pacemakers and defibrillators have become essential tools in the
      armamentarium of electrophysiologists. These procedures are being performed in
      patients with complex comorbidities, many of whom chronically take
      anticoagulation or antiplatelet agents. Careful management of anticoagulation
      before, during, and after electrophysiologic procedures including device
      implantations is critical to minimize bleeding and thrombotic complications and
      to optimize patient outcomes.

PMID- 19846033
TI  - Role of wearable and automatic external defibrillators in improving survival in
      patients at risk for sudden cardiac death.
AB  - Cardiac arrest is a vexing public health problem. Fortunately, implantable
      cardioverter-defibrillators (ICDs) have been proven to decrease overall mortality
      in several populations at high risk for cardiac arrest. However, it is still
      unclear how to treat patients who have an elevated risk of cardiac arrest but are
      not in one of the identified high-risk groups proven to benefit from an ICD. It
      also is uncertain how to manage high-risk patients who have an accepted
      indication for an ICD but are unable or unwilling to have an ICD. In these
      clinical situations, the wearable defibrillator and automatic external
      defibrillator are options that should be considered. Both devices have been shown
      in small series to be highly effective at restoring sinus rhythm in patients with
      a ventricular tachyarrhythmia. However, there is still a lack of large-scale
      trials proving that these devices should be employed routinely in specific high
      risk patient populations.

PMID- 19846034
TI  - Therapeutic implications of automatic home monitoring of implantable cardiac
      devices.
AB  - Electronic cardiac implants such as pacemakers, cardioverter-defibrillators, and
      cardiac resynchronization devices improve survival, as evidenced by recent trials
      for primary and secondary prevention and for cardiac resynchronization therapy.
      As with other forms of therapy, an important aspect of care is monitoring the
      patient's condition, response to therapy, and system function. However, practice
      has been inconsistent. Follow-up schedules vary-for example, from every 3 months
      to once a year-according to facility, physician preference, and availability of
      resources. Importantly, no surveillance occurs between follow-up visits. In
      contrast, implantable devices with remote monitoring capability provide a means
      for performing constant surveillance, with the ability to identify salient
      problems rapidly. Preliminary data from the TRUST (Lumos-T Safely Reduces Routine
      Office Device Follow Up) study demonstrate that this technology provides a means
      for efficient monitoring and an opportunity to enhance patient safety by early
      detection of patient and/or system problems. Remote monitoring likely will become
      incorporated into the standard of care in cardiac implantable electronic devices.

PMID- 19846035
TI  - New and emerging antiarrhythmic drugs for atrial fibrillation: what may become
      available to the clinician in the near future.
AB  - Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major
      cause of morbidity. In the past decade, there have been significant advances in
      the nonpharmacologic management of AF. However, despite these advances there
      continues to be a great need for antiarrhythmic drugs to suppress AF. Existing
      medications have moderate efficacy for AF termination and suppression and have
      significant associated side effects, limiting their use. The need for new
      therapies has spawned the growth of several exciting drugs at various stages of
      development for the medical management of AF. Some agents are derivatives of
      currently available compounds, whereas others have been newly developed to focus
      on novel ion current targets. Dronedarone is the first antiarrhythmic agent in a
      decade to be recommended for approval by the US Food and Drug Administration for
      the management of AF. It is expected to a have a dramatically improved side
      effect profile, which likely will be the key factor in its prominence in our
      armamentarium in the future; however, dronedarone appears to have only moderate
      efficacy. Other novel agents are in various stages of development. Vernakalant,
      an "atrial selective" compound, will be useful in the acute chemical
      cardioversion of AF but not atrial flutter. Although vernakalant is similar in
      efficacy to ibutilide, it carries a significantly reduced risk of torsades de
      pointes. Ranolazine, initially developed for treating chronic angina, has
      important effects on ion currents potentially useful in arrhythmia management.
      Clinical trials specifically studying AF suppression will need to be performed
      before the utility of ranolazine can be extended. It is hoped that as our
      understanding of the pathophysiology of AF improves, innovative targets for
      pharmacologic therapy will emerge. However, the challenge of proving efficacy and
      safety in large randomized controlled trials will remain for any promising new
      agent.

PMID- 19846036
TI  - Acute myocarditis in children: current concepts and management.
AB  - The spectrum of presentation of pediatric myocarditis ranges from minor flu-like
      illness with chest pain to acute cardiogenic shock in a previously healthy child.
      A major change in the diagnostic evaluation of myocarditis is a shift in focus
      away from endomyocardial biopsy and histologic confirmation toward cardiac MRI
      for noninvasive diagnosis and prognostication of acute myocarditis. Cardiac MRI
      may be particularly useful in pediatric patients, considering the risks
      associated with biopsy in children. Some of the MRI characteristics seen in
      pediatric patients with acute myocarditis also may serve as predictors of
      outcome. The approach to managing myocarditis varies according to the severity of
      presentation; it is primarily supportive while spontaneous recovery of cardiac
      function is awaited. For subacute heart failure, the mainstay of therapy is still
      supportive management with oral heart failure medications such as angiotensin
      converting enzyme inhibitors, beta-blockers, and diuretics. Acute myocarditis
      presenting with severe symptomatology, termed fulminant myocarditis, has a high
      recovery rate. Aggressive supportive care, including mechanical circulatory
      support, is indicated in fulminant myocarditis. With the increasing availability
      of and experience with paracorporeal pulsatile mechanical assist devices for
      children, more and more young patients are being bridged to transplantation or
      recovery. Despite promising results from several uncontrolled pediatric studies
      using immunosuppressive and/or immunomodulating therapy with intravenous gamma
      globulin, the translation of these results into a recommended, routine therapy
      for pediatric myocarditis has been complicated by the high rate of spontaneous
      improvement of myocarditis with supportive care and the lack of demonstrable
      benefit for such therapies in blinded, randomized, placebo-controlled trials in
      adult myocarditis. Further clinical studies are necessary to define the possible
      utility of immunosuppressive, immunomodulatory, and antiviral therapy. Heart
      transplantation remains the final therapeutic option for children with
      myocarditis and intractable severe heart failure.

PMID- 19846037
TI  - Current treatment of aortopulmonary window.
AB  - Aortopulmonary window is a rare abnormal congenital communication between the
      pulmonary artery and the ascending aorta with intact aortic and pulmonary valves.
      Because pulmonary hypertension and premature death are the natural history of the
      uncorrected left-to-right shunt physiology that occurs with aortopulmonary
      window, surgical correction, which is the gold standard of treatment, should be
      offered to patients at the time of diagnosis, before the development of lung
      injury and irreversible pulmonary hypertension.

PMID- 19846038
TI  - Ebstein malformation of the tricuspid valve: current concepts in management and
      outcomes.
AB  - Ebstein anomaly is a myopathy of the right ventricle that results in variable
      degrees of failure of delamination of the tricuspid valve leaflets from the
      underlying endocardium, leading to severe tricuspid valve regurgitation and some
      degree of right ventricular dysfunction. In neonates or infants who remain in
      congestive heart failure or profoundly cyanotic while receiving appropriate
      medical therapy, operation is required. Current strategies include biventricular
      or single-ventricle repair. In children and adults, medical management may be
      used, but most patients eventually require surgery. Tricuspid valve repair is
      preferred; we believe the cone repair is the most anatomic repair and is the
      operation of choice. Tricuspid valve replacement may be necessary in cases in
      which the valve is not repairable. A bidirectional cavopulmonary shunt is useful
      in patients with severe right ventricular dilatation and/or dysfunction.
      Transplantation rarely is necessary.

PMID- 19846039
TI  - Pharmaceutical management of decompensated heart failure syndrome in children:
      current state of the art and a new approach.
AB  - Prompt initiation of appropriate and intensive treatment in children with
      decompensated heart failure is crucial to avoid irreversible end-organ
      dysfunction. Initial management of these children includes transfer to the
      pediatric cardiac intensive care unit, basic hemodynamic monitoring, and
      establishment of intravenous access. Inotropic support should be instituted
      peripherally before obtaining central venous and arterial access. The team should
      be prepared for emergent intubation and initiation of mechanical circulatory
      support. Two experienced physicians should work together to obtain vascular
      access and manage sedation, airway control, and cardiovascular support. Acute
      heart failure syndrome in children may be related to cardiomyopathy, myocarditis,
      congenital heart disease, and acute rejection post heart transplantation. Each of
      these causes requires a different approach. Fulminant myocarditis may lead to
      severe morbidity and requires intensive support, although its outcome is
      considered to be good. Acute heart failure related to newly diagnosed dilated
      cardiomyopathy may represent end-stage heart failure; therefore, long-term
      mechanical circulatory support and heart transplantation may be considered to
      avoid other end-organ dysfunction. Hypertrophic cardiomyopathy may lead to acute
      decompensation due to 1) left ventricular outflow obstruction, 2) restrictive
      physiology leading to pulmonary hypertension, or 3) myocardial ischemia
      associated with coronary artery bridging. Decompensated heart failure associated
      with congenital heart disease usually represents end-stage heart failure and
      requires thorough evaluation for heart transplantation. Children with single
      ventricle physiology who develop decompensated heart failure after a Fontan
      procedure are not candidates for mechanical circulatory support and therefore may
      not survive to heart transplantation. Acute heart failure due to
      posttransplantation acute rejection requires aggressive antirejection treatment,
      which places these patients at significant risk for overwhelming opportunistic
      infections. In our opinion, mechanical circulatory support should be initiated
      early in children who present with end-stage heart failure associated with
      hemodynamic instability to avoid end-organ damage.

PMID- 19846040
TI  - Management of postoperative pediatric cardiac arrhythmias: current state of the
      art.
AB  - Postoperative arrhythmias in the pediatric population remain a significant source
      of morbidity and mortality despite advances in surgical techniques. Although our
      understanding of these arrhythmias has improved, the number of therapeutic
      options to treat them has not increased significantly in recent years. However,
      in the specific case of bradyarrhythmias, the use of pacemakers has reduced
      morbidity and mortality significantly. Additionally, various antiarrhythmic
      medications, in conjunction with physiologic maneuvers when necessary, have
      improved our ability to treat postoperative tachyarrhythmias. The prompt
      recognition and proper treatment of postoperative arrhythmias can reduce
      morbidity and mortality for these patients.

PMID- 19846042
TI  - Cognition Disturbances in Psychiatry: Neurobiology and Treatment (In memory of
      David de Wied), May 15-16, 2009, Catalina, Italy.

PMID- 19846041
TI  - Apoptosis induction in BEFV-infected Vero and MDBK cells through Src-dependent
      JNK activation regulates caspase-3 and mitochondria pathways.
AB  - Our previous report demonstrated that bovine ephemeral fever virus (BEFV)
      infected cultured cells could induce caspase-dependent apoptosis. This study aims
      to further elucidate how BEFV activates the caspase cascade in bovine cells. BEFV
      replicated and induced apoptosis in Vero and Madin-Darby bovine kidney (MDBK)
      cells, and a kinetic study showed a higher efficiency of replication and a
      greater apoptosis induction ability of BEFV in Vero cells. Src and c-Jun N
      terminal kinase (JNK) inhibitor, but not extracellular signal-regulated kinase
      (ERK) or p38 inhibitor, alleviated BEFV-mediated cytopathic effect and apoptosis.
      In BEFV-infected Vero and MDBK cells, BEFV directly induced Src tyrosine-418
      phosphorylation and JNK phosphorylation and kinase activity, which was inhibited
      specifically by SU6656 and SP600125, respectively. The caspase cascade and its
      downstream effectors, Poly (ADP-ribose) polymerase (PARP) and DFF45, were also
      activated simultaneously upon BEFV infection. In addition, cytochrome c, but not
      Smac/DIABLO, was released gradually from mitochondria after BEFV infection.
      SU6656 suppressed Src, JNK, and caspase-3 and -9 activation, as well as PARP and
      DFF45 cleavage; SP600125 reduced JNK and caspase-3 and -9 activation, as well as
      PARP and DFF45 cleavage. Taken together, these results strongly support the
      hypothesis that a Src-dependent JNK signaling pathway plays a key role in BEFV
      induced apoptosis. The molecular mechanism identified in our study may provide
      useful information for the treatment of BEFV.

PMID- 19846043
TI  - Polaprezinc, a zinc compound, is distributed to the lingual epithelium and
      increases its zinc concentration in zinc-deficient rats.
AB  - AIMS: To clarify the mechanism underlying the effect of polaprezinc on
      hypogeusia, we investigated the uptake of polaprezinc by the tongue in rats. MAIN
      METHODS: Rats were fed a zinc-sufficient (Zn(+)) or zinc-deficient (Zn(-)) diet.
      After 4weeks on the Zn(-) diet, polaprezinc (1, 3, or 10mg/kg) or [(65)Zn]
      polaprezinc (10mg/kg) was administered orally once a day. The zinc concentration
      or the (65)Zn radioactivity of the tongue was measured by inductively-coupled
      plasma mass spectrometry or gamma counting, respectively. In addition, the
      distribution of (65)Zn in the tongue was analyzed by microautoradiography and the
      proliferative activity of taste bud cells was measured from the uptake of 5-bromo
      2'-deoxyuridine. KEY FINDINGS: The zinc concentration of the lingual epithelium,
      but not the whole tongue, was markedly decreased in Zn(-) rats compared with
      Zn(+) rats. After administration of polaprezinc to Zn(-) rats at doses of 1, 3,
      and 10mg/kg, the zinc concentration in the lingual epithelium increased
      significantly from 85+/-4 to 105+/-7 (p<0.05), 120+/-3 (p<0.001), and 124+/-3
      (p<0.001) microg/g, respectively. After administration of [(65)Zn] polaprezinc,
      the (65)Zn radioactivity of the tongue and serum were higher in Zn(-) rats than
      in Zn(+) rats. (65)Zn was mainly detected in the epithelium on
      microautoradiograms of the tongue in Zn(-) rats. In addition, polaprezinc (3 and
      10mg/kg) improved the reduced proliferation of taste bud cells due to zinc
      deficiency. SIGNIFICANCE: Polaprezinc is distributed to the lingual epithelium
      and restores its zinc concentration in Zn(-) rats resulting in improvement of
      cellular functions, especially proliferation.

PMID- 19846044
TI  - Tolerance to ethanol sedation and withdrawal hyper-excitability is mediated via
      neuropeptide Y Y1 and Y5 receptors.
AB  - AIMS: Neuropeptide Y (NPY) is widely distributed throughout the brain and has
      been implicated in some of the actions of ethanol. The aim of the present study
      was to characterize the subtypes of NPY receptors in ethanol induced sedation,
      tolerance and withdrawal hyper-excitability. MAIN METHODS: The loss of righting
      reflex paradigm was used to record the sleep duration in mice. KEY FINDINGS: The
      acute administration of ethanol (3-4g per kg, i.p., 20%v/v) resulted in marked
      sedation. While prolonged ethanol consumption led to the development of
      tolerance, the mice showed hyper-excitability following ethanol withdrawal. Prior
      acute intracerebroventricular (i.c.v.) injection of NPY (5-20 ng per mouse) or
      NPY Y1 and Y5 receptors agonist [Leu(31), Pro(34)]-NPY (0.02-0.2 ng per mouse)
      potentiated ethanol induced sedation. On the other hand, administration of
      selective NPY Y1 receptor antagonist BIBP3226 (5 ng per mouse, i.c.v.) inhibited
      ethanol induced sedation. Chronic concomitant treatment of NPY (20 ng per mouse,
      i.c.v.) or [Leu(31), Pro(34)]-NPY (0.2 ng per mouse, i.c.v.) to ethanol-fed
      groups prevented the development of tolerance and attenuated withdrawal hyper
      excitability. Moreover, acute treatment of NPY (5 ng per mouse, i.c.v.) or
      [Leu(31), Pro(34)]-NPY (0.02 ng per mouse, i.c.v.) reversed the peak ethanol
      withdrawal hyper-excitability. SIGNIFICANCE: The results underscore a role for
      NPY Y1 and Y5 receptors in the ethanol induced sedation, tolerance and withdrawal
      hyper-excitability. We suggest that modulation of NPY Y1 and Y5 receptors may be
      a strategy to address the ethanol withdrawal conditions.

PMID- 19846045
TI  - Altered regulation of renal nitric oxide, atrial natriuretic peptide and
      cyclooxygenase systems in aldosterone escape in rats.
AB  - The present study was aimed to determine whether there is an altered role of
      local nitric oxide (NO), atrial natriuretic peptide (ANP) and cyclooxygenase
      (COX) systems in the kidney in association with the aldosterone escape. Male
      Sprague-Dawley rats were used. Aldosterone (200 microg/day) was infused through
      entire time course. The control group was kept on a low sodium diet (0.02
      mEq/day), and the experimental group was supplied with a higher sodium diet (2.
      /day). Four days after beginning the regimen, the kidneys were taken. The protein
      expression of NO synthase (NOS) and COX isoforms was determined by
      semiquantitative immunoblotting. The mRNA expression of components of ANP system
      was determined by real-time polymerase chain reaction. The activities of soluble
      and particulate guanylyl cyclases were determined by the amount of cGMP generated
      in responses to sodium nitroprusside and ANP, respectively. There developed
      aldosterone escape in the experimental group. Accordingly, the renal content and
      the urinary excretion of NO increased. The expression of nNOS was increased in
      the inner medulla. Neither the expression of eNOS nor that of iNOS was changed.
      The expression and the catalytic activity of soluble guanylyl cyclase remained
      unaltered. The mRNA expression of ANP was increased. Neither the expression of
      NPR-A or NPR-C nor the activity of particulate guanylyl cyclase was altered in
      the papilla. The protein expression of COX-2 was increased in the inner medulla,
      while that of COX-1 remained unchanged. In conclusion, the upregulation of nNOS,
      ANP, and COX-2 may be causally related with the aldosterone escape.

PMID- 19846046
TI  - Comparison of the performance of two mycobacteriophage D29-based protocols for
      fluoroquinolone susceptibility testing in Mycobacterium tuberculosis.
AB  - We tested a mycobacteriophage D29-based method for fluoroquinolone susceptibility
      assessment in clinical isolates of Mycobacteriumtuberculosis. The method was
      incapable of identifying susceptible strains as such, although a slightly
      different published protocol successfully identified resistant and susceptible
      strains. Thus, caution is necessary when choosing an "in-house" D29-based
      protocol for testing of drug resistance.

PMID- 19846047
TI  - Chronic psychosocial stress alters NPY system: different effects in rat and tree
      shrew.
AB  - The neuropeptide Y (NPY) system has been largely studied in relation to affective
      disorders, in particular for its role in the mechanisms regulating the
      pathophysiology of anxiety and depression and in the stress-related behaviours.
      Although NPY has been previously investigated in a variety of animal models of
      mood disorders, the receptor subtype mainly involved in the modulation of the
      stress response has not been identified. In the present study, the chronic
      psychosocial stress based on the resident-intruder protocol-an ethologically
      relevant paradigm known to induce behavioural and endocrine modifications which
      mimic depression-like symptoms-was used. Two different species were investigated:
      rat and tree shrew (Tupaia belangeri); the latter is regarded as an intermediate
      between insectivores and primates and it was chosen in this study for its
      pronounced territoriality. In these animals, the regulation of NPY and of Y(1),
      Y(2) and Y(5) receptors mRNA expression was evaluated after chronic stress and
      chronic antidepressant treatment by in situ hybridization in selected brain
      regions known to be involved in the pathophysiology of mood disorders. The
      animals were exposed to psychosocial stress for 35 days and concomitant daily
      fluoxetine treatment (10 mg/kg for rats and 15 mg/kg for tree shrews) after the
      first week of stress. The results confirmed a major role for hippocampal and
      hypothalamic NPY system in the pathophysiology of mood disorders. Although there
      were no evident differences between rat and tree shrew in the NPY system
      distribution, an opposite effect of chronic psychosocial stress was observed in
      the two species. Moreover, chronic antidepressant treatment was able to
      counteract the effects of stress and restored basal expression levels, suggesting
      the utility of these paradigms as preclinical models of stress-induced
      depression. Overall, although evident species differences were found in response
      to chronic psychosocial stress, the present study suggests a role for NPY
      receptors in the stress response and in the action of antidepressant drugs,
      providing further support for an involvement of this neuropeptidergic system in
      the pathophysiology of depression and anxiety.

PMID- 19846048
TI  - Effects of chronic oral acrylamide exposure on incremental repeated acquisition
      (learning) task performance in Fischer 344 rats.
AB  - Acrylamide (ACR) is a relatively potent neurotoxicant. The ingestion of
      carbohydrate-containing foods cooked at high temperature exposes humans to low
      levels of ACR virtually daily. At relatively high levels of exposure (i.e., sub
      chronic through chronic levels of exposure of >or=20mg/kg body weight/day), ACR
      has been shown in both rats and humans to produce a variety of effects on the
      nervous system. The possibility that chronic dietary exposure to ACR might
      produce brain toxicity which could impede the development of learning skills is a
      question of current concern. This research evaluated the effects of ACR on
      learning task performance in Fischer 344 rats exposed daily beginning prenatally
      and continuing throughout the lifespan. Dams were gavaged with ACR since
      implantation [gestation day (GD) 6] with 0, 0.1, 0.3, 1.0 or 5.0mg/kg/day through
      parturition. Gavaging continued at the same doses to pups through weaning on post
      natal day (PND) 22 after which dosing continued via their drinking water. One
      male and one female per litter (8-9 per treatment group) were tested. Using an
      incremental repeated acquisition (IRA) task to assess learning ability, ACR
      exposed Fischer 344 rats exhibited altered performance by 4 months of age. From
      approximately 1-8 months of age (through approximately PND 240), over 52 testing
      sessions, a significant treatment effect was found on percent task completed
      (PTC), with Tukey's post-hoc test (P<0.05) indicating a significantly lower PTC
      for the 5.0mg/kg/day group compared to controls. While there was no treatment
      effect on accuracy (P=0.53), a significant decrease in response rate was seen at
      5.0mg/kg/day, suggesting that the noted decrease in PTC was due to a decrease in
      rate of responding, not to an effect on accuracy of task solution. Previous
      findings in these same animals performing a progressive ratio task for the
      assessment of motivation, as well as a range of tests of motoric function,
      suggest that this decreased response rate could be due to subtle motoric effects,
      or possibly due to decreases in psychomotor speed, but is most likely due to
      motivational effects.

PMID- 19846049
TI  - Fluctuations in Rayleigh breakup induced by particulates.
AB  - A jet of liquid is intrinsically unstable to radial perturbations and will
      spontaneously break to form a series of droplets. This well known instability,
      the Rayleigh-Plateau instability, is controlled and used commercially in
      continuous inkjet printing. In this application it is important that fluctuations
      in drop velocity are minimised. However, the addition of particulates to the
      liquid is observed to strongly increase these fluctuations. The particulates are
      usually in the form of pigment particles of size O(100 nm) and at a concentration
      where they may hydrodynamically interact, particularly in the strong shear field
      within the nozzle (O(10(7) s(-1))). The boundary layer thickness within the
      nozzle is O(1 MUm) and therefore the particulate size is a significant fraction.
      We therefore expect that the particles are capable of perturbing the boundary
      layer and hence the jet. Measurement of jet breakup fluctuation leads to a
      description of particulates interacting within and with the shear field
      associated with the boundary layer at the nozzle wall.

PMID- 19846051
TI  - Vascularization in first-trimester chorionic villi in complicated and
      uncomplicated pregnancies.
AB  - OBJECTIVE: The purpose of this study was to investigate possible altered
      chorionic vascularization patterns that are seen already in the first trimester
      of pregnancies that are complicated by hypertensive disorders or intrauterine
      growth restriction (IUGR) in the third trimester of pregnancy. STUDY DESIGN:
      After chorionic villous sampling, surplus of villi were stored, and a selection
      was made of pregnancies that were complicated further by hypertensive disorders
      (n = 26), normotensive IUGR (n = 13), and matched control subjects (n = 60).
      Vascular parameters of these villi were analyzed with a video-image-analysis
      system. RESULTS: In pregnancies that are complicated by early-onset hypertensive
      disorders and IUGR, the mean distance of the peripheral vessels to the
      intervillous space and the total of the distances (central and peripheral) are
      significantly smaller, compared with control subjects (9.3% and 13.8% for
      hypertensive disorders and 12.2% and 16.1% for IUGR, respectively). CONCLUSION:
      Differences in vascularization patterns in the placenta already in the first
      trimester of pregnancies that are complicated later by hypertensive disorders or
      IUGR confirm the hypothesis of early changes by means of more vessels and more
      peripheral vessels that are located in chorionic villi.

PMID- 19846050
TI  - Implications of vitamin D deficiency in pregnancy and lactation.
AB  - Vitamin D is an essential fat soluble vitamin and a key modulator of calcium
      metabolism in children and adults. Because calcium demands increase in the third
      trimester of pregnancy, vitamin D status becomes crucial for maternal health,
      fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D
      deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%),
      despite the widespread use of prenatal vitamins, because these are inadequate to
      maintain normal vitamin D levels (>or=32 ng/mL). Adverse health outcomes such as
      preeclampsia, low birthweight, neonatal hypocalcemia, poor postnatal growth, bone
      fragility, and increased incidence of autoimmune diseases have been linked to low
      vitamin D levels during pregnancy and infancy. Studies are underway to establish
      the recommended daily doses of vitamin D in pregnant women. This review discusses
      vitamin D metabolism and the implications of vitamin D deficiency in pregnancy
      and lactation.

PMID- 19846052
TI  - Do multivitamin supplements modify the relationship between prenatal alcohol
      intake and miscarriage?
AB  - OBJECTIVE: To determine whether multivitamin supplements modify the relationship
      between alcohol consumption during pregnancy and the risk of miscarriage. STUDY
      DESIGN: We used data from a population-based cohort study of pregnant women
      (n=1061; response rate=39%). Participants were asked about their alcohol
      consumption and vitamin intake during pregnancy. RESULTS: Among multivitamin
      nonusers, women who drank alcohol during their pregnancy were more likely to have
      a miscarriage compared with women who abstained (adjusted hazard ratio, 1.67; 95%
      confidence interval, 1.04-2.69). However, among multivitamin users, there was no
      difference in the risk of miscarriage between alcohol consumers and abstainers.
      Results suggest the volume of alcohol as well as the timing of multivitamin
      supplementation may also be important. CONCLUSION: Our findings suggest that a
      woman of childbearing years might decrease her risk of miscarriage associated
      with alcohol intake by taking multivitamin supplements. However, our findings
      should be interpreted with caution and future research replicating these findings
      is necessary.

PMID- 19846053
TI  - Examining the effectiveness of an opt-in approach to prenatal human
      immunodeficiency virus screening.
AB  - OBJECTIVE: We sought to determine the prenatal human immunodeficiency virus (HIV)
      screening rate when using an opt-in policy and to find variables predictive of
      screening. STUDY DESIGN: This was a case-control study examining gravid women
      with a prenatal visit and a delivery at our hospital in 2005. Cases were defined
      as women who did not undergo HIV screening during the first or second prenatal
      visit. Our institution used an opt-in approach to HIV screening. RESULTS:
      Overall, 71% (291/412) of women underwent HIV screening at the first or second
      prenatal visit. Patient refusal was the most common reason for not being screened
      (15%; 62/412). Women who were < or = 25 years old, were unmarried, and received
      care from maternal-fetal medicine attendings or family practitioners were more
      likely to undergo HIV screening. CONCLUSION: With an opt-in approach, 29% of
      women were not screened for HIV during their early prenatal care. An opt-in
      policy also leads to screening rates that are provider dependent.

PMID- 19846054
TI  - Prediction of spontaneous preterm birth in asymptomatic twin pregnancies using
      the change in cervical length over time.
AB  - OBJECTIVE: We sought to evaluate the change in cervical length (CL) as a
      predictor of preterm birth in asymptomatic twin pregnancies. STUDY DESIGN: We
      studied a historical cohort of 121 twin pregnancies with CL testing between 18-24
      weeks who had a follow-up CL 2-6 weeks after the initial CL. RESULTS: A total of
      19 patients had their CL decrease by > or = 20% (shortened CL group) and 102
      patients' CL decreased by less, or not at all (stable CL group). The shortened CL
      group had a significantly higher rate of spontaneous preterm birth <28 weeks, <30
      weeks, <32 weeks, and <34 weeks. This remained true even when excluding patients
      with a short CL (< or = 25 mm) on the repeated CL. CONCLUSION: In twin
      pregnancies, a CL that decreases by 20% over 2 measurements is a significant
      predictor of very preterm birth, even in the setting of a normal CL. Serial CL
      measurements should be considered in twin pregnancies, starting <24 weeks.

PMID- 19846055
TI  - Outcome and complications of retropubic and transobturator midurethral slings
      translated into surgical therapeutic indices.
AB  - OBJECTIVE: We sought to determine and compare surgical therapeutic indices (STIs)
      of the retropubic tension-free vaginal tape (TVT) and 2 kinds of transobturator
      tape (TOT), Monarc (American Medical Systems, Minneapolis, MN), and tension-free
      vaginal tape obturator. STUDY DESIGN: This was a retrospective cohort study.
      Patients with predominant stress urinary incontinence who underwent retropubic
      (TVT, n = 257) or TOT (n = 180) procedures were included. STIs for both groups
      were calculated by dividing cure by complication rate at, respectively, 2 and 12
      months. RESULTS: Two months after surgery the STI was significantly higher after
      TOT whereas 12 months after surgery results of STIs were equal. The explanation
      is more durable cure rates and declining long-term side effects after TVT
      procedures. CONCLUSION: Both surgical approaches seem to have their own benefits.
      Based on the STI, the balance between cure rate and complications is on the short
      term in favor of TOT but on the long term similar for TOT and retropubic TVT.

PMID- 19846057
TI  - Appraisal of the selectivity index in a cohort of patients treated with laser
      surgery for twin-twin transfusion syndrome.
AB  - OBJECTIVE: The selectivity index (SI) has been proposed as a measure of technical
      success in laser surgery for twin-twin transfusion syndrome. Surgeries with an
      index >-0.25 have been considered highly selective. The purpose of this study was
      to evaluate the applicability of this index in our patient population. STUDY
      DESIGN: The SI was assessed in 314 consecutive laser surgeries and correlated
      with perinatal survival. RESULTS: A total of 310 patients (98.7%) underwent a
      completely selective procedure. The SI was 0.8 in the selective laser
      photocoagulation of communicating vessels group vs 0.3 in the nonselective laser
      photocoagulation of communicating vessels group (P = .001). In the selective
      group perinatal survival of at least 1 twin (92.6% vs 50%) and survival of the
      donor (75.4% vs 0%) was significantly better (P = .05). CONCLUSION: The SI as
      originally proposed is misleading and of limited use as it does not differentiate
      selective from nonselective procedures. We propose instead using a ratio of
      selective/nonselective procedures, and selectively coagulated/total number of
      coagulated vessels to appraise center-specific and patient-specific surgical
      performance of laser surgery for twin-twin transfusion syndrome.

PMID- 19846058
TI  - Reflections on the possible role of the methionine synthase reductase (MTRR) A66G
      polymorphism as a maternal risk factor for Down syndrome in Italy.

PMID- 19846059
TI  - Long-term outcome of idiopathic macular hole surgery.
AB  - PURPOSE: To evaluate the role of preoperative macular hole (MH) diameter,
      cataract surgery, and cystoid macular edema (CME) in the reopening of idiopathic
      macular hole (IMH) after initially successful surgery. DESIGN: Multicenter,
      retrospective, comparative case series. METHODS: One hundred and thirty patients
      (135 eyes) with stage 2, 3, or 4 IMH were included after successful IMH repair at
      Dijon University Hospital or Nancy University Hospital. The eyes were separated
      into 4 groups according to the lens status: group 1, vitrectomy in pseudophakic
      eyes; group 2, vitrectomy and cataract extraction as a combined procedure; group
      3, vitrectomy followed by cataract extraction; group 4, vitrectomy on eyes that
      remained phakic. All patients underwent a complete vitrectomy with retinal inner
      limiting membrane peeling and intraocular gas tamponade. The main outcome
      measures were IMH closure rate and best-corrected visual acuity. RESULTS: Mean
      duration of symptoms was 8.6 +/- 7.6 months. The follow-up was 37 +/- 8.6 months
      (range, 30 to 67 months). The mean preoperative IMH diameter was 454 +/- 191 mum.
      No MH reopened during the follow-up after the initial vitreous surgery. Seven
      cases of CME were observed (1 in groups 1 and 2; 5 in group 3), and cataract
      surgery was performed in the 53 patients in group 3 with a mean delay of 11.6
      months. CONCLUSIONS: Cataract extraction, CME, or preoperative MH diameter
      measured by optical coherence tomography were not identified as risk factors for
      IMH reopening.

PMID- 19846060
TI  - Ocular surface squamous neoplasia after corneal graft.
AB  - PURPOSE: To describe the clinical features and management of ocular surface
      squamous neoplasia (OSSN) after corneal graft. DESIGN: Retrospective case series
      of 4 patients. METHODS: Four eyes of 4 patients treated for OSSN after corneal
      graft in an institutional setting were included. All 4 patients were treated with
      topical chemotherapy and additionally 1 patient each was treated with excisional
      biopsy and photodynamic therapy. The main outcome measure was the recurrence of
      OSSN and the clarity of corneal graft after treatment. RESULTS: The mean time
      interval between corneal graft and diagnosis of OSSN was 36 months (range, 2 to
      73 months). All 4 eyes were on chronic treatment with topical steroids for a
      minimum duration of 2 months and 2 eyes had previous herpes keratitis.
      Misdiagnosis of graft rejection was found in 2 cases. The mean tumor basal
      diameter was 18 mm (range, 14- to 25-mm) and the tumor involved a mean of 76% of
      the corneal surface (range, 15% to 90%). Management was successful in all cases
      using topical mitomycin C (n = 1), topical interferon alpha2b (n = 4), and
      photodynamic therapy (n = 1). At mean follow-up of 20 months, tumor control was
      achieved in all cases and all 4 eyes showed chronic graft opacification with
      vascularization but no intraocular tumor. CONCLUSION: Corneal OSSN should be
      considered in patients using chronic topical steroids for corneal graft.
      Nonsurgical management with topical chemotherapy or photodynamic therapy can
      achieve tumor control.

PMID- 19846061
TI  - Two-year visual results for older Asian women treated with photodynamic therapy
      or bevacizumab for myopic choroidal neovascularization.
AB  - PURPOSE: To compare the long-term visual and anatomic outcome of treatment with
      photodynamic therapy (PDT) or intravitreal bevacizumab (IVB; Avastin; Genentech
      Inc, South San Francisco, California, USA) for choroidal neovascularization
      attributable to pathologic myopia (mCNV). DESIGN: An open-label, interventional
      case series. METHODS:  SETTING: Multi-institutional. PATIENTS: Thirty-one eyes of
      Japanese women who received either PDT or IVB for mCNV. Inclusion criteria were
      age 50 years or older, greatest linear dimension (GLD) 1200 to 3000 microm, and
      baseline best-corrected visual acuity (BCVA) 20/200 to 20/40. INTERVENTION
      PROCEDURES: Patients received either PDT or IVB (1 mg/40 microL) throughout the
      study, with re-treatment when necessary. MAIN OUTCOME MEASURES: BCVA and visual
      gain/loss at 3, 6, 12, 18, and 24 months after the initial treatment. RESULTS:
      Age, BCVA, location of CNV, refractive error, and symptom duration at baseline
      did not differ significantly between groups. BCVA was significantly improved at 3
      to 12 months (P < .05); however, the significance was lost at 18 and 24 months in
      the IVB group. The PDT group showed no significant improvement within the first
      year, and vision slowly worsened after 12 months, becoming significantly worse at
      18 and 24 months compared to baseline (P< .01). BCVA was significantly higher in
      the IVB group at 6 months (P< .05), and 12 months or further (P < .01). Visual
      gain was significantly greater in the IVB group at 6, 12, 18, and 24 months (P <
      .05 for 6, 18, and 24 months and P < .01 for 12 months). CONCLUSIONS: These
      findings indicate that the effects of PDT and IVB have a different time course,
      and that IVB provides a significantly better BCVA than PDT for mCNV over the long
      term.

PMID- 19846062
TI  - Uncoupling the D1-N-methyl-D-aspartate (NMDA) receptor complex promotes NMDA
      dependent long-term potentiation and working memory.
AB  - BACKGROUND: Although dopamine D1 receptors are involved in working memory, how D1
      receptors contribute to this process remains unclear. Numerous studies have shown
      that D1 receptors have extensive functional interaction with N-methyl-D-aspartate
      (NMDA) receptor. Our group previously demonstrated that D1 receptors were able to
      regulate NMDA receptor functions through direct protein-protein interactions
      involving the carboxyl terminals of D1 receptors and NMDA receptor NR1a and NR2A
      subunits respectively. In this study, we explored the effects of the D1-NR1
      interaction on NMDA receptor-dependent long-term potentiation (LTP) and working
      memory by using the TAT-conjugated interfering peptide (TAT-D1-t2). METHODS:
      Miniature excitatory postsynaptic currents are recorded in rat hippocampal
      primary cultures. Coimmunoprecipitation and calcium/calmodulin-dependent protein
      kinase II (CaMKII) activity are measured in hippocampal slices and hippocampal
      neurons under the specified experimental conditions, respectively. Working memory
      was assessed using a delayed match-to-place protocol in the Morris Water Maze
      following administration of the TAT-D1-t2 peptide. RESULTS: Electrophysiology
      experiments showed that activation of D1 receptor upregulates NMDA receptor
      mediated LTP in a CaMKII-dependent manner. Furthermore, D1 receptor agonist
      stimulation promotes the NR1-CaMKII coupling and enhances the CaMKII activity;
      and the D1 receptor-mediated effects can be blocked by the application of the TAT
      D1-t2 peptide. Interestingly, animals injected with TAT-D1-t2 peptide exhibited
      significantly impaired working memory. CONCLUSIONS: Our study showed a critical
      role of NMDA-D1 direct protein-protein interaction in NMDA receptor-mediated LTP
      and working memory and implicated the involvement of CaMKII in this process.

PMID- 19846064
TI  - Functional magnetic resonance imaging of inner speech in schizophrenia.
AB  - BACKGROUND: Auditory verbal hallucinations in schizophrenia have been linked to
      defective monitoring of one's own verbal thoughts. Previous studies have shown
      that patients with auditory verbal hallucinations show attenuated activation of
      brain regions involved with auditory processing during the monitoring of inner
      speech. However, there are no functional magnetic resonance imaging studies
      explicitly comparing the perception of external speech with internal speech in
      the same patients with schizophrenia. The present study investigated the
      functional neuroanatomy of inner and external speech in both patients with
      schizophrenia and healthy control subjects. METHODS: Fifteen patients with
      schizophrenia and 12 healthy control subjects were studied using functional
      magnetic resonance imaging while listening to sentences or imagining sentences.
      RESULTS: Significant interactions between group (control subjects vs. patients)
      and task (listening vs. inner speech) were seen for the left superior temporal
      gyrus, as well as regions within the cingulate gyrus. CONCLUSIONS: Attenuated
      deactivation of the left superior temporal gyrus in schizophrenia patients during
      the processing of inner speech may reflect deficits in the forward models
      subserving self-monitoring.

PMID- 19846063
TI  - Subgenual prefrontal cortex activity predicts individual differences in
      hypothalamic-pituitary-adrenal activity across different contexts.
AB  - BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) system activation is adaptive in
      response to stress, and HPA dysregulation occurs in stress-related
      psychopathology. It is important to understand the mechanisms that modulate HPA
      output, yet few studies have addressed the neural circuitry associated with HPA
      regulation in primates and humans. Using high-resolution F-18-fluorodeoxyglucose
      positron emission tomography (FDG-PET) in rhesus monkeys, we assessed the
      relation between individual differences in brain activity and HPA function across
      multiple contexts that varied in stressfulness. METHODS: Using a logical AND
      conjunctions analysis, we assessed cortisol and brain metabolic activity with FDG
      PET in 35 adolescent rhesus monkeys exposed to two threat and two home-cage
      conditions. To test the robustness of our findings, we used similar methods in an
      archival data set. In this data set, brain metabolic activity and cortisol were
      assessed in 17 adolescent male rhesus monkeys that were exposed to three stress
      related contexts. RESULTS: Results from the two studies revealed that subgenual
      prefrontal cortex (PFC) metabolism (Brodmann's area 25/24) consistently predicted
      individual differences in plasma cortisol concentrations regardless of the
      context in which brain activity and cortisol were assessed. CONCLUSIONS: These
      findings suggest that activation in subgenual PFC may be related to HPA output
      across a variety of contexts (including familiar settings and novel or
      threatening situations). Individuals prone to elevated subgenual PFC activity
      across multiple contexts may be individuals who consistently show heightened
      cortisol and may be at risk for stress-related HPA dysregulation.

PMID- 19846065
TI  - New findings on extinction of conditioned fear early in development: theoretical
      and clinical implications.
AB  - Research with adult animals suggests that extinction depends, at least partly, on
      new inhibitory learning that is specific to the context in which it is learned.
      However, several recent studies show that extinction processes are dissociated
      across development. The present article reviews research on the behavioral and
      neurobiological mechanisms underlying extinction in developing rats. To
      summarize, postweanling aged rats (i.e., 24-day-olds) display adult-like
      extinction in that they show renewal, reinstatement, spontaneous recovery, and
      compound summation of extinguished stimuli. However, preweanling aged rats (i.e.,
      17-day-olds) do not show any of those behavioral phenomena. Pharmacological
      studies also show that reducing N-methyl-D-aspartate, gamma-aminobutryic acid,
      and opioid neurotransmission impairs extinction in 24-day-old rats, but
      extinction in P17 rats is only affected by the blocking of opioid
      neurotransmission. Lastly, extinction in 24-day-old rats involves the amygdala
      and the ventromedial prefrontal cortex (vmPFC), which are critical brain areas in
      the neural circuitry of extinction in adult rats. Interestingly, extinction in 17
      day-old rats involves the amygdala but not the vmPFC. The existing models of
      extinction cannot account for these developmental differences. These findings
      showing that distinct processes mediate extinction at different stages of
      development may have significant clinical implications, which are discussed in
      this review.

PMID- 19846066
TI  - Cocaine-specific antibodies blunt the subjective effects of smoked cocaine in
      humans.
AB  - BACKGROUND: Rates of relapse among cocaine-dependent patients are high, and new
      treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine
      (TA-CD) produces selective anticocaine antibodies, yet the impact of these
      antibodies on cocaine's direct effects is unknown. The objective of this human
      laboratory study was to measure the relationship between antibody titers and the
      effects of smoked cocaine on ratings of intoxication, craving, and cardiovascular
      effects. METHODS: Ten cocaine-dependent men not seeking drug treatment spent 2
      nights per week for 13 weeks inpatient where the effects of cocaine (0 mg, 25 mg,
      50 mg) were determined before vaccination and at weekly intervals thereafter. Two
      doses of TA-CD (82 microg, n = 4; 360 microg, n = 6) were administered at weeks
      1, 3, 5, and 9. RESULTS: Peak plasma antibody levels, which were highly variable,
      significantly predicted cocaine's effects. Those individuals in the upper half of
      antibody production had an immediate (within 4 minutes of cocaine smoking) and
      robust (55%-81%) reduction in ratings of good drug effect and cocaine quality,
      while those in the lower half showed only a nonsignificant attenuation (6%-26%).
      Self-reported cocaine use while participants were outpatient tended to decrease
      as a function of antibody titer (p < .12). By contrast, higher antibody levels
      predicted significantly greater cocaine-induced tachycardia. CONCLUSIONS: The TA
      CD vaccine substantially decreased smoked cocaine's intoxicating effects in those
      generating sufficient antibody. These data support further testing of cocaine
      immunotherapy as a treatment for cocaine dependence.

PMID- 19846068
TI  - Remission of major depression under deep brain stimulation of the lateral
      habenula in a therapy-refractory patient.

PMID- 19846069
TI  - Macoma birmanica agglutinin recognizes glycoside clusters of beta-GlcNAc/Glc and
      alpha-Man.
AB  - Macoma birmanica agglutinin (MBA) that seems to play crucial roles in the innate
      immunity of marine bivalve, M. birmanica has been earlier defined as GlcNAc/Man
      specific. However, most complementary carbohydrate structures to its binding
      domain and ligand clustering in its recognition profile have not been
      established. In this study, the complete recognition profile of MBA was examined
      by enzyme-linked lectin-sorbent assay and inhibition assay. Among the
      monosaccharides tested, GlcNAc was more reactive followed by Man and Glc, others
      were non-reactive; revealing the importance of equatorial -NAc group at C-2, -OH
      group at C-4 and C-6, and pyranose conformation of hexose. Moreover, beta
      glycosides of GlcNAc and Glc were more potent whereas for Man it was alpha
      glycoside. MBA recognized both exposed and internal alpha-Man and beta-GlcNAc/Glc
      residues well with most linkages except (beta1-4). This binding pattern was
      further extended and confirmed by polyvalent glycoside clusters of GlcNAc(beta1
      2)Man(alpha1-, which was a better inhibitor than Man(alpha1-2/3/6)Man(alpha1- or
      Man(alpha1-3/6)Man(beta1- present in well-defined naturally occurring
      glycoproteins. This broad range specificity explains the importance of MBA as an
      important pattern recognition molecule that provides more realistic picture of
      carbohydrate-based immune response triggering.

PMID- 19846067
TI  - A genomewide association study of citalopram response in major depressive
      disorder.
AB  - BACKGROUND: Antidepressant response is likely influenced by genetic constitution,
      but the actual genes involved have yet to be determined. We have carried out a
      genomewide association study to determine whether common DNA variation influences
      antidepressant response. METHODS: Our sample is derived from Level 1 participants
      in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, all
      treated with citalopram. Association for the response phenotype included 883
      responders and 608 nonresponders. For the remission phenotype, 743 subjects that
      achieved remission were compared with 608 nonresponders. We used a subset of
      single nucleotide polymorphisms (SNPs; n = 430,198) from the Affymetrix 500K and
      5.0 Human SNP Arrays, and association analysis was carried out after correcting
      for population stratification. RESULTS: We identified three SNPs associated with
      response with p values less than 1 x 10(-5) near the UBE3C gene (rs6966038, p =
      4.65 x 10(-7)), another 100 kb away from BMP7 (rs6127921, p = 3.45 x 10(-6)), and
      a third that is intronic in the RORA gene (rs809736, p = 8.19 x 10(-6)). These
      same SNPs were also associated with remission. Thirty-nine additional SNPs are of
      interest with p values < or = .0001 for the response and remission phenotypes.
      CONCLUSIONS: Although the findings reported here do not meet a genomewide
      threshold for significance, the regions identified from this study provide
      targets for independent replication and novel pathways to investigate mechanisms
      of antidepressant response. This study was not placebo controlled, making it
      possible that we are also observing associations to nonspecific aspects of drug
      treatment of depression.

PMID- 19846070
TI  - Prescribed spatial prepositions influence how we think about time.
AB  - Prepositions combine with nouns flexibly when describing concrete locative
      relations (e.g. at/on/in the school) but are rigidly prescribed when paired with
      abstract concepts (e.g. at risk; on Wednesday; in trouble). In the former case
      they do linguistic work based on their discrete semantic qualities, and in the
      latter they appear to serve a primarily grammatical function. We used the
      abstract concept of time as a test case to see if specific grammatically
      prescribed prepositions retain semantic content. Using ambiguous questions
      designed to interrogate one's meaningful representation of temporal relations, we
      found that the semantics of prescribed prepositions modulate how we think about
      time. Although prescribed preposition use is unlikely to be based on a core
      representational organization shared between space and time, results demonstrate
      that the semantics of particular locative prepositions do constrain how we think
      about paired temporal concepts.

PMID- 19846071
TI  - Psychophysical thresholds of face visibility during infancy.
AB  - The ability to detect and focus on faces is a fundamental prerequisite for
      developing social skills. But how well can infants detect faces? Here, we address
      this question by studying the minimum duration at which faces must appear to
      trigger a behavioral response in infants. We used a preferential looking method
      in conjunction with masking and brief presentations (300 ms and below) to
      establish the temporal thresholds of visibility at different stages of
      development. We found that 5 and 10 month-old infants have remarkably similar
      visibility thresholds about three times higher than those of adults. By contrast,
      15 month-olds not only revealed adult-like thresholds, but also improved their
      performance through memory-based strategies. Our results imply that the
      development of face visibility follows a non-linear course and is determined by a
      radical improvement occurring between 10 and 15 months.

PMID- 19846072
TI  - Immediate truth--temporal contiguity between a cognitive problem and its solution
      determines experienced veracity of the solution.
AB  - A temporal contiguity hypothesis for the experience of veracity is tested which
      states that a solution candidate to a cognitive problem is more likely to be
      experienced as correct the faster it succeeds the problem. Experiment 1 varied
      the onset time of the appearance of proposed solutions to anagrams (50 ms vs. 150
      ms) and found for both correct and incorrect candidates that faster appearing
      solutions were more frequently judged as being correct, although participants
      were not aware of the difference in onset delay. Experiment 2 replicated this
      effect with mathematical equations, shorter onset latencies (0 ms vs. 50 ms), and
      a reversed sequence (presenting first the solution and then the problem).
      Experiment 3 showed that the probability of judging a word as the solution of a
      remote associate insight problem decreases linearly with increasing onset delay
      (50 ms, 150 ms, 300 ms). Possible neurobiological-cognitive explanations for this
      effect are proposed.

PMID- 19846073
TI  - Exogenous phasic alerting and spatial orienting in mild cognitive impairment
      compared to healthy ageing: Study outcome is related to target response.
AB  - Whether or not attentional mechanisms such as phasic alerting, spatial cueing and
      inhibition of return (IOR) remain intact in adults with Alzheimer's disease (AD)
      and mild cognitive impairment (MCI) remains a matter of debate. This is possibly
      the result of inter-study outcome variation caused by the adoption of different
      methodological components by different research groups. Here we investigated the
      influence of methodological factors upon study outcome, using a Posner-type
      exogenous cueing paradigm with amnestic MCI patients and healthy older controls.
      Specifically, we compared results when the required response involved target
      discrimination with results for a simple target detection response, using cue-to
      target intervals (CTIs) of 200msec and 800msec in each case and with the same
      participants completing all conditions. For both groups, the presence or absence
      of both alerting and spatial cue-related effects depended upon the combination of
      target response requirement and CTI. Moreover, differences between the groups
      were specific to certain task conditions. The MCI group showed the same alerting
      effects as healthy people with a discrimination response, but the alerting effect
      shown by controls with a 200msec CTI and target detection was absent in MCI.
      Patients and controls showed similar spatial cue validity effects at 200msec CTI,
      but group differences emerged at 800msec CTI: target discrimination evoked a
      validity effect in the MCI group only, while target detection evoked an IOR
      effect in the healthy group only. These data indicate that detection and
      discrimination responses may each activate different attentional mechanisms,
      which are themselves differentially vulnerable in MCI. Thus a seemingly arbitrary
      choice of response may directly influence whether attentional processing appears
      preserved or disrupted in MCI. Furthermore, these data provide further evidence
      in support of the existence of significant visual attention-related functional
      abnormalities in amnestic MCI.

PMID- 19846074
TI  - Letter position dysgraphia.
AB  - The article describes AE, a Hebrew-speaking individual with acquired dysgraphia,
      who makes mainly letter position errors in writing. His dysgraphia resulted from
      impairment in the graphemic buffer, but unlike previously studied patients, most
      of his errors related to the position of letters rather than to letter identity:
      80% of his errors were letter position errors in writing, and only 7% of his
      errors were letter omissions, substitutions, and additions. Letter position
      errors were the main error type across tasks (writing to dictation and written
      naming), across output modalities (writing and typing), and across stimuli, e.g.,
      migratable words (words in which letter migration forms another word), irregular
      words, and nonwords. Letter position errors occurred mainly in the middle letters
      of a word. AE's writing showed a significant length effect, and no lexicality,
      migratability, or frequency effects. His letter position deficit was manifested
      selectively in writing; he made no letter position errors in reading,
      demonstrating the dissociability of letter position encoding in reading and
      writing. These data support the existence of a letter order function in the
      graphemic buffer that is separate from the function responsible for activating
      letter identities.

PMID- 19846075
TI  - Practice Committee documents: an effort to improve practice.

PMID- 19846076
TI  - EUS-guided in vivo microdialysis of the pancreas: a novel technique with
      potential diagnostic and therapeutic application.
AB  - BACKGROUND: Microdialysis has been used in vivo to measure dynamic temporal
      variations in extracellular or interstitial concentrations of non-protein-bound
      substances that are unstable in the systemic circulation. OBJECTIVE: To evaluate
      the technical feasibility and possible complications of EUS-guided in vivo
      microdialysis of the pancreas. DESIGN AND INTERVENTION: Under the guidance of an
      echoendoscope inserted into the stomach of each dog, the pancreatic parenchyma
      was punctured by using a 19-gauge needle. A specially developed microdialysis
      probe threaded through the lumen of the 19-gauge needle was positioned in the
      pancreas. The probe was constantly perfused with saline solution at a flow rate
      of 1.0 microL/minute. SETTING: Experiments on 8 beagle dogs. MAIN OUTCOME
      MEASUREMENTS: The concentration of 5-fluorouracil (5-FU) in the microdialysate
      was measured at 10-minute intervals, once before and for 8 times after a single
      (20 mg/kg) bolus intravenous infusion of 5-FU. RESULTS: Following the
      administration of 5-FU, the concentration of 5-FU in all macrodialysate samples
      exceeded the cut-off value by more than 100-fold. The 5-FU levels in the
      microdialysate increased rapidly, peaked by 10 minutes (13.9 microg/mL), and
      gradually declined thereafter. No local bleeding or accumulation of fluid around
      the pancreas was observed. LIMITATION: Sampling was unsuccessful in 2 of the 8
      dogs because the probe broke while being inserted into the pancreatic parenchyma.
      CONCLUSION: EUS-guided pancreatic microdialysis is feasible and has multiple
      potential clinical/therapeutic applications, including monitoring
      pharmacokinetics focally and detecting novel biomarkers that are unstable or
      undetectable in the plasma.

PMID- 19846077
TI  - Imaging of subsquamous Barrett's epithelium with ultrahigh-resolution optical
      coherence tomography: a histologic correlation study.
AB  - BACKGROUND: Optical coherence tomography (OCT) is being developed as a
      potentially valuable method for high-resolution cross-sectional imaging of the
      esophageal mucosal and submucosal layers. One potential application of OCT
      imaging is to identify subsquamous Barrett's epithelium in patients who have
      undergone ablative therapy, which is not visible on standard endoscopic
      examination. However, histologic correlation confirming the ability of OCT to
      image subsquamous Barrett's epithelium has yet to be performed. DESIGN:
      Histologic correlation study. OBJECTIVE: To perform histologic correlation of
      ultrahigh-resolution optical coherence tomography (UHR-OCT) imaging for
      identification of subsquamous Barrett's epithelium. SETTING: Academic Medical
      Center (University of Washington, Seattle, WA). PATIENTS: Fourteen patients with
      pathologic biopsy specimens, proven to be high-grade dysplasia or adenocarcinoma
      underwent esophagectomy. INTERVENTIONS: UHR-OCT imaging was performed on ex vivo
      esophagectomy specimens immediately after resection. MAIN OUTCOME MEASUREMENTS:
      Correlation of UHR-OCT images with histologic images. RESULTS: Subsquamous
      Barrett's epithelium was clearly identified by using UHR-OCT images and was
      confirmed by corresponding histology. LIMITATIONS: Difficulty distinguishing some
      subsquamous Barrett's glands from blood vessels in ex vivo tissue (because of the
      lack of blood flow) in some cases. Imaging was performed with a bench-top system.
      CONCLUSIONS: Results from this study demonstrate that UHR-OCT imaging is capable
      of identifying subsquamous Barrett's epithelium.

PMID- 19846078
TI  - Loop-anchor purse-string versus endoscopic clips for gastric closure: a natural
      orifice transluminal endoscopic surgery comparison study using burst pressures.
AB  - BACKGROUND: The success of natural orifice surgery depends on a reliable, secure
      closure of the opening in the gut. Few tests of the integrity of these closures
      have been published. OBJECTIVE: To determine whether a gastrotomy can be closed
      safely and effectively from within the stomach by using looped T-anchors-a novel,
      endoscopically placed device. DESIGN: Head-to-head comparison trial of 2 closure
      methods in 9 explanted porcine stomachs. SETTING: Animal laboratory.
      INTERVENTION: Paired gastrotomies were made in porcine explants. One was closed
      by using endoscopic clips, and the other was closed by using modified T-anchors
      in a purse-string fashion. MAIN OUTCOME MEASUREMENTS: Gastric transmural pressure
      gradients at bursting of these closures were measured while the explanted
      stomachs were inflated with a high-pressure insufflator. RESULTS: The mean burst
      pressure of the looped T-anchors was 27.3 mm Hg, whereas that of the clip
      closures was 14 mm Hg. By using 10 mm Hg as a threshold for a "secure" closure, 7
      of 9 clip closures failed to meet the threshold value, whereas all 9 of the T
      anchor closures met or exceeded the threshold value (P = .0023, 2-tailed Fisher
      exact test). LIMITATION: Nonsurvival study. CONCLUSION: Looped T-anchors provide
      a secure gastric closure for natural orifice surgery and are superior to
      endoscopic clips for this purpose.

PMID- 19846079
TI  - Primary aortoduodenal fistula: a rare cause of upper GI bleeding.

PMID- 19846080
TI  - Radiological imaging of the GI tract after bariatric surgery.
AB  - BACKGROUND: Obesity is becoming epidemic in proportion and is leading to
      considerable morbidity and mortality in the community. Bariatric surgery offers
      one tested solution to sustained weight loss and comorbidity reduction. However,
      it is associated with a significant number of complications. OBJECTIVE: The
      objective of this article is to review the utility of radiological techniques in
      the diagnosis of surgical complications after bariatric surgery. DESIGN:
      Literature-based review and pictorial illustration in the use of imaging
      techniques in the diagnosis of complications after bariatric surgery.
      CONCLUSIONS: Radiology plays a critical role in the diagnosis of complications
      after bariatric surgery. Upper GI contrast study and CT are the most commonly
      used imaging modalities in this regard. They are complementary in their
      diagnostic abilities and should be used in concert for the complete evaluation of
      symptomatic patients. All other radiological imaging modalities are also used in
      the diagnosis of complications after bariatric surgery, but much less commonly.

PMID- 19846081
TI  - Autoimmune pancreatitis presenting with IgG4-positive multiple gastric polyps.

PMID- 19846082
TI  - Population-based prevalence estimates of history of colonoscopy or sigmoidoscopy:
      review and analysis of recent trends.
AB  - BACKGROUND: Lower GI endoscopy, such as colonoscopy or sigmoidoscopy, is thought
      to have a substantial impact on colorectal cancer incidence and mortality through
      detection and removal of precancerous lesions and early cancers. We aimed to
      review prevalence estimates of history of colonoscopy or sigmoidoscopy in the
      general population and to analyze recent trends. METHODS: A systematic review of
      the medical literature, including MEDLINE (1966 to August 2008) and EMBASE (1980
      to August 2008), was undertaken, supplemented by searches of the European Health
      Interview & Health Examination Surveys database and bibliographies. Detailed age
      specific and sex-specific prevalence estimates from the United States were
      obtained from the Behavioral Risk Factor Surveillance System surveys 2002, 2004,
      and 2006. RESULTS: The search yielded 55 studies that met our inclusion criteria.
      The majority of the reports (43) originated from the United States. Other
      countries of origin included Australia (2), Austria (2), Canada (5), France (1),
      Germany (1), and Greece (1). Estimates from the United States were generally
      increasing over time up to 56% (2006) for lifetime use of colonoscopy or
      sigmoidoscopy in people aged 50 years and older. Analysis of national survey data
      showed higher prevalences among men aged 55 years and older than for women of the
      same age. Prevalences were highest for people aged 70 to 79 years. CONCLUSION:
      Data from outside the United States were extremely limited. Prevalence estimates
      from the United States indicate that a considerable and increasing proportion of
      the population at risk has had at least 1 colonoscopy or sigmoidoscopy in their
      lives, although differences between age and sex groups persist. Prevalences of
      previous colonoscopy or sigmoidoscopy need to be taken into account in the
      interpretation of time trends in, and variation across, populations of colorectal
      cancer incidence and mortality.

PMID- 19846083
TI  - Crohn's disease of the esophagus with esophagobronchial fistula formation: a case
      report and review of the literature.

PMID- 19846084
TI  - Jejunal and ileal thickening caused by Taenia saginata diagnosed by double
      balloon endoscopy (with video).

PMID- 19846085
TI  - Laparoscopy-assisted ERCP: experience of a high-volume bariatric surgery center
      (with video).
AB  - BACKGROUND: Laparoscopy-assisted ERCP (LAERCP) allows the diagnosis and treatment
      of biliopancreatic conditions in patients with Roux-en-Y anatomy (RY). However,
      experience with this technique is limited. OBJECTIVES: To report on the
      experience with LAERCP in consecutive patients from a high-volume bariatric
      surgery center and to evaluate success rates of ERCP with the laparoscopy
      assisted approach. DESIGN: Retrospective case series. SETTING: High-volume
      bariatric surgery center. PATIENTS: Consecutive patients undergoing LAERCP
      between 2003 and 2009. INTERVENTION: LAERCP. OUTCOMES: Immediate/delayed
      complications, biliary/pancreatic duct cannulation, endoscopic/laparoscopic
      interventions, postprocedure hospital stay, procedure duration. RESULTS: Ten
      patients underwent LAERCP: 9 after Roux-en-Y gastric bypass (RYGB) and 1 after
      antrectomy with RY (9 female, 1 male; 9 white, 1 black). Indications for the
      procedure were choledocholithiasis (n=4), biliary stricture (n=3), and sphincter
      of Oddi dysfunction (n=3). Endoscopic access was obtained to the gastric remnant
      (n=9) or biliopancreatic limb (n=1). Biliary cannulation was successfully
      achieved in 9 of 10 patients, biliary sphincterotomy was performed in all,
      pancreatography in 3 of 3, and sphincter of Oddi manometry in 2. In 1 patient, a
      3F pancreatic duct stent was placed prophylactically. Mild post-ERCP pancreatitis
      developed in 2 patients, and 1 patient had a pneumothorax intraoperatively that
      was treated successfully. The mean duration of the procedure was 89 minutes
      (range 41-245), and the median postprocedure hospital stay was 2 days (mean 2.59,
      standard deviation 2.46). LIMITATIONS: Single-center, retrospective design.
      CONCLUSION: LAERCP is safe and successful for the diagnosis and therapy of
      biliopancreatic conditions in patients with RY. It additionally allows the
      diagnosis and treatment of internal hernias, a known complication of RYGB.

PMID- 19846086
TI  - Endoscopic glue injection for persistent biliary leakage.

PMID- 19846087
TI  - Diagnosis of pancreatic neoplasia with EUS and FNA: a report of accuracy.
AB  - BACKGROUND: EUS-guided FNA has the potential to provide diagnostic cytologic
      material from pancreatic lesions that are suspicious for malignancy. OBJECTIVE:
      To determine the operating characteristics of EUS-FNA in the diagnosis of
      pancreatic adenocarcinoma and pancreatic neuroendocrine neoplasms (PENs). DESIGN:
      Retrospective analysis of a prospectively maintained database. SETTING: Academic
      tertiary-care center. PATIENTS: This study involved 559 patients undergoing
      evaluation of pancreatic masses or diffuse pancreatic parenchymal abnormalities.
      MAIN OUTCOME MEASUREMENTS: Performance characteristics of EUS-FNA of pancreatic
      adenocarcinoma and PEN. RESULTS: From January 1997 to December 2005, 737 patients
      undergoing initial EUS-FNA evaluation for a pancreatic mass were identified. In
      the final analysis, 559 patients with 560 FNA-sampled lesions were included.
      Overall, 442 lesions were pancreatic adenocarcinoma, and 40 were PEN. The
      sensitivity of EUS-FNA in the diagnosis of pancreatic adenocarcinomas and PENs
      was 77% (95% CI, 72.8%-80.8%) and 68% (95% CI, 50.8%-80.9%), respectively, using
      strict cytologic criteria. Reclassification of atypical and suspicious cytologies
      as diagnostic of malignancy resulted in a sensitivity of 93%, (95% CI, 90.9%
      99.7%) in adenocarcinoma and 80% (95% CI, 63.9%-90.4%) in PEN. Tumor size, tumor
      location, and number of needle passes did not significantly influence diagnosis,
      but immediate cytologic evaluation was influential. LIMITATIONS: Retrospective
      analysis at a single center. CONCLUSIONS: In a large, well-controlled study, EUS
      FNA was found to be an accurate test (80%) for the detection of pancreatic
      adenocarcinoma by using aspiration cytology. The accuracy of the examination is
      significantly improved (94%) when atypical and suspicious samples are considered
      positive. Finally, only 2 to 3 FNA passes may be needed to achieve a good
      diagnostic yield.

PMID- 19846088
TI  - Where there is no anesthetist--increasing capacity for emergency obstetric care
      in rural India: an evaluation of a pilot program to train general doctors.
AB  - OBJECTIVE: The lack of anesthesia providers in rural public sector hospitals is a
      significant barrier to providing emergency obstetric care. In 2006, the state of
      Gujarat initiated the Life Saving Anesthetic Skills (LSAS) for Emergency
      Obstetric Care (EmOC) training program for medical offers (MOs). We evaluated the
      trained MOs' experience of the program, and identified factors leading to post
      training performance. METHODS: The sample was chosen to equally represent
      performing and nonperforming LSAS-trained MOs using purposive sampling
      qualitative interviews with trainees across Gujarat (n=14). Data on facility
      preparedness and monthly case load were also collected. RESULTS: Being posted
      with a specialist anesthesiologist and with a cooperative EmOC provider increased
      the likelihood that the MOs would provide anesthesia. MOs who did not provide
      anesthesia were more likely to have been posted with a nonperforming or
      uncooperative EmOC provider and were more likely to have low confidence in their
      ability to provide anesthesia. Facilities were found to be under prepared to
      tackle emergency obstetric procedures. CONCLUSION: Program managers should
      consider extending the duration of the program and placing more emphasis on
      practical training. Posting doctors with cooperative and performing EmOC
      providers will significantly improve the effectiveness of the program. A separate
      team of program managers who plan, monitor, and solve the problems reported by
      the trained MOs would further enhance the success of scaling up the training
      program.

PMID- 19846089
TI  - Using audits to reduce the incidence of uterine rupture in a Malawian district
      hospital.
AB  - OBJECTIVES: To improve obstetric care and reduce the incidence of uterine rupture
      through the use of audits. METHODS: Data were collected from medical records and
      from questioning women who sustained uterine rupture over a 12-month period in
      Thyolo District Hospital, Malawi. Audit sessions were performed every 2-3 weeks
      for the first 3 months with relevant members of the hospital staff, after which
      an extended audit was held with input from two external expert obstetricians.
      Cases were also audited by the principal investigator for delays in referral,
      diagnosis, and treatment. RESULTS: Thirty-five cases of uterine rupture were
      diagnosed at the facility during the study period. Sixteen ruptures were
      diagnosed during the first 3 months, an incidence of 19.2 per 1000 deliveries.
      Following audit and implementation of recommendations, the incidence of uterine
      rupture decreased by 68% (OR 0.32; 95% CI, 0.16-0.63) to 6.1 per 1000 deliveries
      over the next 9 months. The overall case fatality rate was 11.4%, and the
      perinatal mortality rate was 829 per 1000 live births. CONCLUSIONS: Audit is an
      inexpensive, appropriate, and effective intervention to improve the quality of
      facility-based maternal care and decrease the incidence of uterine rupture in low
      resource settings. Ensuring constructive self-criticism, continuous professional
      learning, and good participation by district health managers in audit sessions
      may be important requirements for their success.

PMID- 19846090
TI  - Saving mothers and newborns through an innovative partnership with private sector
      obstetricians: Chiranjeevi scheme of Gujarat, India.
AB  - OBJECTIVE: To document an innovative public-private partnership between the
      government of Gujarat, India and private obstetricians in rural areas that
      provides delivery care to the poor. METHODS: This is a descriptive analysis of
      the scheme and analysis of secondary data. We estimate the lives of mothers and
      newborns potentially saved because of the scheme. RESULTS: More than 800
      obstetricians have joined the scheme and more than 269000 poor women have
      delivered in private facilities in 2 years. We estimate that the percentage of
      institutional deliveries among poor women increased from 27% to 48% between April
      2007 and September 2008. In addition, there are fewer reported maternal and
      newborn deaths among the beneficiaries compared with the number of deaths
      expected in the absence of the scheme. CONCLUSIONS: This innovative program shows
      that, at least in some areas of India, it is possible to develop a large scale
      partnership with the private sector to provide skilled birth attendance and
      emergency obstetric care to poor women at a relatively low cost. This is one way
      of addressing the human resource deficit in the public sector in rural areas of
      low-income countries to achieve Millennium Development Goals 4 and 5. We also
      conclude that the skilled care thus provided can reduce maternal and neonatal
      mortality among the poor.

PMID- 19846091
TI  - Where there is no obstetrician--increasing capacity for emergency obstetric care
      in rural India: an evaluation of a pilot program to train general doctors.
AB  - BACKGROUND: Maternal mortality continues to be high in rural India. Chief among
      the reasons for this is a severe shortage of obstetricians to perform cesarean
      delivery and other skills required for emergency obstetric care (EmOC). In 2006,
      the Government of India and the Federation of Obstetric and Gynecological
      Societies of India (FOGSI) with technical assistance from Jhpiego, instituted a
      nationwide, 16-week comprehensive EmOC (CEmOC) training program for general
      medical officers (MOs). This program is based on an earlier pilot project (2004
      2006). OBJECTIVE: To evaluate the pilot project, and identify lessons learned to
      inform the nationwide scale-up. METHODS: The lead author (CE) visited trainees
      and their facilities to evaluate the project. Eight data collection tools were
      created, which included interviews with informants (program/government staff,
      regional/international experts, trainees and trainers), facility observation, and
      facility-based data collection of births and maternal/newborn deaths during the
      study period. RESULTS: More trainees performed each of the basic EmOC skills
      after the training than before. After training, 10 of 15 facilities to which
      trainees returned could provide all signal functions for basic EmOC whereas only
      2 could do so before. For comprehensive EmOC, 2 facilities with obstetricians
      were providing all functions before and 2 were doing so after, even though the
      specialists had left those facilities and services were being provided by CEmOC
      trainees. Barriers to providing, or continuing to provide, EmOC for some trainees
      included insufficient training for cesarean delivery, lack of anesthetists,
      equipment and infrastructure (operating theater, blood services, forceps/vacuum,
      manual vacuum aspiration syringes). CONCLUSION: Although MOs can be trained to
      provide CEmOC (including cesarean delivery), without proper selection of
      facilities and trainees, adequate training, and support, this strategy will not
      substantially improve the availability of comprehensive EmOC in India.
      RECOMMENDATIONS: To implement a successful nationwide scale-up, several steps
      should be taken. These include, selecting motivated trainees, implementing the
      training as it was designed, improving support for trainees, and ensuring
      appropriate staff and infrastructure for trainees at their facilities before they
      return from training.

PMID- 19846092
TI  - Early ambulation--consider working with physiotherapists. A comment on Cortes et
      al. (2009).

PMID- 19846093
TI  - [Surgical techniques of appendectomy for acute appendicitis].
AB  - Over the last 20 years, the treatment of acute appendicitis has been transformed
      by the development of the laparoscopic approach. And yet the net value of this
      approach continues to be debated. Laparoscopic appendectomy is associated with a
      lower complication rate and a shorter period of disability in the general
      population. While operative costs are higher, the global cost of laparoscopic
      appendectomy is lower than for open appendectomy. There is a somewhat higher rate
      of abdominal abscess for the laparoscopic route. Laparoscopic appendectomy shows
      clear advantages in obese patients and in those with gangrenous or ruptured
      appendicitis. The laparoscopic approach is contra-indicated during pregnancy due
      to a higher incidence of miscarriage. Treatment of the appendiceal stump by
      ligature decreases the expense associated with the use of a surgical stapler.
      When Meckel's diverticulum is encountered during appendectomy, it should be
      removed in all pediatric patients; in adults, Meckel's diverticulectomy in adults
      should be performed only for clear-cut pathology. Surgeons continue to innovate
      and refine appendectomy techniques but many questions remain to be answered.

PMID- 19846094
TI  - [Can acute appendicitis be treated by antibiotics and in what conditions?].
AB  - The current treatment for acute appendicitis is an appendectomy. Several studies
      have, however, assessed the efficacy of an antibiotic for treating acute
      appendicitis that is either uncomplicated or complicated by local peritonitis. A
      meta-analysis in 2007 that collected the results of 44 prospective studies showed
      that antibiotics were efficacious in 92.8% of cases of appendicitis complicated
      by local peritonitis, with percutaneous drainage of an abscess when necessary. No
      predictive factor for failure was identified. The failure of antibiotic treatment
      did not increase morbidity. Over time and on the whole, the recurrence rate was
      only 8.9%. The risk of cancer of the appendix (1.5%) nonetheless led to the
      recommendation of an interval appendectomy for adults. Four randomized controlled
      trials have compared antibiotic treatment with an appendectomy for the treatment
      of uncomplicated acute appendicitis. The efficacy of the antibiotic treatment
      ranged from 86 to 100% and the recurrence rate from 10.4 to 35%. These studies
      have had various methodological impediments; however, too few patients were
      included (40 and 80 patients), or only a clinical diagnosis was made before
      inclusion, or important protocol violations occurred, in particular for almost
      half the patient in the antibiotic therapy group in the 2009 study. These
      problems prevent us from relying on these authors' findings. Antibiotics have a
      role in the initial treatment of acute appendicitis complicated by local
      peritonitis. In uncomplicated acute appendicitis, the methodological inadequacy
      of the currently available randomized trials makes it impossible to reach a
      definitive conclusion about the efficacy of antibiotics.

PMID- 19846095
TI  - [The pediatric surgeon and acute appendicitis].
AB  - The management of acute appendicitis in the pediatric patient has undergone
      radical rethinking in recent years. It has been shown that simple uncomplicated
      acute appendicitis can be successfully managed with antibiotic therapy and may
      not even require interval appendectomy. Appendicitis complicated by perforation,
      abscess, or inflammatory phlegmon can be successfully treated by initial
      antibiotic therapy (with or without percutaneous drainage) and delayed interval
      appendectomy. While the laparoscopic approach has proved to be well-adapted to
      many other pediatric surgical procedures, its utility in the treatment of
      uncomplicated acute appendicitis remains open to debate; compared to standard
      open appendectomy, it offers only minimal advantages with regard to post
      operative care, length of hospital stay, and complications. Children can be
      managed either by general surgeons or pediatric surgeons depending on the
      organization of the emergency service; there may be a higher incidence of removal
      of a normal appendix in non-specialized services.

PMID- 19846096
TI  - [Ultrasound and CT imaging in the diagnosis of acute appendicitis].
AB  - The diagnosis of acute appendicitis is still made on the basis of clinical
      findings in the majority of cases. When the clinical picture is unclear,
      ultrasound examination is a simple and effective tool to confirm the diagnosis.
      When ultrasound is unsatisfactory due to patient habitus or otherwise fails to
      clarify clinical uncertainty, abdominopelvic CT scan yields excellent results in
      terms of both sensitivity and specificity. While recognizing these evidence-based
      results, the surgeon must remain pragmatic and realize that the quality of each
      exam depends on the quality of the examination and the experience of the
      radiologist.

PMID- 19846097
TI  - [Medical students in Paris during the Commune (March 28-May 28, 1871)].

PMID- 19846099
TI  - [Appendiceal tumors found at appendectomy].
AB  - There are three main histologic types of appendiceal tumor: adenoma,
      adenocarcinoma, and neuroendocrine tumor. Neuroendocrine tumors (carcinoids) are
      by far the most common and account for two-third of all appendiceal tumors.
      Adenomas and adenocarcinomas are both rare; they share two particularities: (a) a
      mucinous component is both frequent and predominant, (b) they have a tendency to
      intraperitoneal dissemination. Rupture of any mucinous tumor-whether spontaneous
      or occurring during surgery-may result in pseudomyxoma peritonei; treatment of
      this condition requires complete resection of all lesions followed by
      hyperthermic intraperitoneal chemotherapy. For unruptured appendiceal tumor, the
      appendix should be removed by a carcinologic right hemicolectomy if the tumor
      appears aggressive.

PMID- 19846100
TI  - [The usefulness of scores in the diagnosis of appendicitis].
AB  - The diagnosis of acute appendicitis relies largely on clinical experience; the
      performance of complementary tests is oftentimes unnecessary. We have created a
      score based on clinical and laboratory findings which can reliably categorize
      three zones of diagnostic probability : probable, doubtful, or improbable. Only
      the intermediate category requires complementary imaging. Alvarado first
      developed a scoring system based on operative findings and this has been modified
      and improved by others. In our experience, the scoring system of Francois has
      been most useful. This score is based on simple clinical data and findings such
      as age, sex, duration of symptoms, leucocytosis, palpable mass on rectal exam,
      and urinary symptoms. We have validated this score in a cohort of 202 patients
      presenting with right lower quadrant abdominal pain and found a sensitivity of
      94.7% and a negative predictive value of 97.4% for patients falling into the
      probable and improbable categories. Management of patients with either very high
      or very low scores can proceed more expeditiously and with less expense.
      Diagnostic imaging can be reserved for those patients with intermediate scores
      where the diagnosis is in doubt. We have established a clinical pathway in our
      emergency department based on this scoring system.

PMID- 19846101
TI  - Comparison of molecularly imprinted, mixed-mode and hydrophilic balance sorbents
      performance in the solid-phase extraction of amphetamine drugs from wastewater
      samples for liquid chromatography-tandem mass spectrometry determination.
AB  - Recent studies have shown that amphetamines and other drugs of abuse residues
      occur in wastewater. Consequently, several methods have been developed for their
      determination by solid-phase extraction (SPE) and liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). However, a major drawback of these methods is the
      lack of selectivity during SPE that results in reduced sensitivity, due to matrix
      effects, and in some cases in low precision and poor accuracy. In order to tackle
      this problem, three different SPE alternatives have been evaluated in this work
      for the determination of five amphetamines: common hydrophilic balance (Oasis
      HLB), mixed-mode (Oasis MCX) and molecularly imprinted polymers (MIPs) sorbents.
      Among them, Oasis HLB showed the worst performance, as three amphetamines (MDA,
      MDMA and MDEA) could not be determined because of interfering signals in the LC
      MS/MS chromatogram, and amphetamine recoveries could not be corrected by the use
      of the deuterated analogue internal standard. Oasis MCX permitted the
      determination of all target analytes, but with still strong signal suppression:
      ca. 70% signal drop with wastewater samples, which could in this case be
      corrected by the internal standards providing acceptable trueness (overall
      recoveries: 101-137%), precision (RSD: 2.0-12%) and limits of detection (LOD: 1.5
      4.4 ng/L). Alternatively, MIPs rendered cleaner extracts with less matrix effects
      (ca. 30% signal drop), and thus lower LODs (0.5-2.7 ng/L) and even better
      trueness (91-114% overall recovery) and precision (1.5-4.4%RSD). The final
      application of the method with MIP cartridges showed the presence of MDA and MDMA
      in the seven analysed wastewaters at the 4-20 ng/L level.

PMID- 19846102
TI  - New asymmetrical per-substituted cyclodextrins (2-O-methyl-3-O-ethyl- and 2-O
      ethyl-3-O-methyl-6-O-t-butyldimethylsilyl-beta-derivatives) as chiral selectors
      for enantioselective gas chromatography in the flavour and fragrance field.
AB  - Asymmetrically substituted 6(I-VII)-O-t-butyldimethylsilyl(TBDMS)-3(I-VII)-O
      ethyl-2(I-VII)-O-methyl-beta-cyclodextrin (MeEt-CD) and 6(I-VII)-O-TBDMS-2(I-VII)
      O-ethyl-3(I-VII)-O-methyl-beta-cyclodextrin (EtMe-CD) were synthesised to
      evaluate the role of the substitution pattern in positions 2 and 3 on the
      enantioselectivity, in particular in view of their application to routine
      analysis in fast enantioselective gas chromatography (Es-GC). The chromatographic
      properties and enantioselectivities of the new derivatives were tested by
      separating the enantiomers of a series of medium-to-high volatility racemates in
      the flavour and fragrance field, and compared to those of the corresponding
      symmetrically substituted 6(I-VII)-O-TBDMS-2(I-VII),3(I-VII)-O-methyl-beta-CD
      (MeMe-CD) and 6(I-VII)-O-TBDMS-2(I-VII),3(I-VII)-O-ethyl-beta-CD (EtEt-CD), and
      were then applied to analysis of real-world essential oil (e.o.) samples. A new
      synthetic process including the sonochemical approach to obtain synthetic
      reproducibility and significant yields of the per-substituted derivatives with
      acceptable reaction times was developed. The results show that asymmetrically
      substituted methyl/ethyl CDs compared to the methyl or ethyl symmetrical
      derivatives in general provide better enantioselectivity in terms of both
      enantiomer resolution and number of separated chiral compounds, and show how the
      substitution pattern in positions 2 and 3 of the CD ring can influence the
      separation. Moreover, these new CD derivatives with better enantioselectivity are
      also shown to be very useful in routine analysis for the exhaustive control of
      samples containing several chiral characterizing markers in a single run.

PMID- 19846103
TI  - Fast ion chromatography using short anion exchange columns.
AB  - A fast ion chromatographic system is described which uses shorter column lengths
      and compares various eluent profiles in order to maximise the performance without
      sacrificing the chromatographic resolution. Both isocratic and gradient elution
      profiles were considered to find the most efficient mode of separation. The
      separation and determination of seven target anions (chloride, chlorate, nitrate,
      chromate, sulfate, thiocyanate and perchlorate) was achieved using a short (4mm
      ID, 50mm long) column packed with Dionex AS20 high-capacity anion exchange
      material. A hydroxide eluent was used at an initial concentration of 25 mM (at a
      flow-rate of 1.0 mL/min) and two performance maxima were found. The maximum
      efficiency occurred at a normalised gradient ramp rate of 5mM/t(0), resulting in
      a peak capacity of 16, while the fastest separation (<3 min) occurred at a
      normalised ramp rate of 30 mM/t(0). The retention time, peak width and resolution
      using the different eluent profiles on varying column lengths is also compared.
      Further investigations in this study determined that the highest peak capacity
      separation under gradient conditions could be approximated using an isocratic
      separation. The advantage of using this novel approach to approximate the maximum
      efficiency separation removes the need for column re-equilibration that is
      required for gradient elution resulting in faster analyses and enhanced sample
      throughput, with benefits in particular for multidimensional chromatography.

PMID- 19846104
TI  - Unusual buffer action of free-standing nanoscopically confined water.
AB  - The acid-base properties of nanoscopic water confined in the black soap films
      (BSFs), which were prepared from aqueous solutions of sodium dodecylsulphate
      (SDS) with the dye neutral red (NR) as a pH probe, were investigated using a
      combination of UV-vis and FTIR spectroscopy. For the SDS micellar solutions at pH
      1.0-9.5 adjusted with HCl/NaOH solutions and at pH 9.4 with ammonium buffered
      solution, the aqueous core thicknesses in the corresponding BSFs ranged from 2.7
      to 6.2 nm, and the nanoscopically confined water exhibits unusual buffer action
      resistant not only to acidic/alkaline solutions but also to standard buffer
      solution. In the heavily water-depleted confined zones, it is most likely that
      charge pairs in proton-transfer reactions could not be formed effectively and
      proton transfer was prohibited in the absence of sufficient solvating ability.
      Theoretical analyzes indicated that the buffer action of the nanoscopic water
      originated from the confinement effect of two charged surfaces of the BSFs. These
      results might inspire deeper understanding and further studies of biobuffering,
      enzyme superactivity, acid-catalyzed reactions, and Nafion fuel cell membranes.

PMID- 19846105
TI  - Plasmonic photocatalytic system using silver chloride/silver nanostructures under
      visible light.
AB  - Plasmonic photocatalytic nanostructured system was investigated on silver
      chloride/silver nanoparticles under visible light. Silver chloride/silver
      nanoparticles were readily prepared using dispersing agent and light irradiation.
      The d-spacing analysis, high resolution-transmission electron microscopy, X-ray
      diffraction analysis and diffuse-reflectance spectroscopy demonstrated that
      silver nanoparticles were introduced on the surface of silver chloride
      nanoparticles and then silver chloride/silver nanostructured photocatalytic
      materials were successfully synthesized. The as-synthesized plasmonic
      photocatalysts exhibited the enhanced photocatalytic performance over nitrogen
      doped titania nanomaterials. The improved catalytic activity was originated from
      the enhanced adsorption for visible light, electron-hole separation, and the
      formation of chloride atoms in silver chloride/silver nanostructured materials.

PMID- 19846106
TI  - Low-molecular-weight gelators based on N(alpha)-acetyl-N(epsilon)-dodecyl-L
      lysine and their amphiphilic gelation properties.
AB  - A simple amphiphilic low-molecular-weight gelator based on L-lysine, N(alpha)
      acetyl-N(epsilon)-lauroyl-L-lysine (1), its alkali metal salts [Na (2) and K
      (3)], and two-component gelators [1 and 2 and 1 and 3] were synthesized. Compound
      1 had a good hydrogelation ability that formed a pure water gel at 2 g L(-1) (0.2
      wt.%) and a saline gel at 4 g L(-1) (0.4 wt.%). Two-component compounds were able
      to form hydrogels in aqueous solutions containing alkali metal and alkali earth
      metal ions in addition to pure water and saline. Although 1 formed organogels in
      a few organic solvents, two-component compounds also functioned as a good
      organogelator. The FT-IR study indicated that the driving forces for the
      formation of supramolecular gels were hydrogen-bonding and hydrophobic
      interactions. Furthermore, the thermal properties of the hydrogels are discussed.

PMID- 19846107
TI  - Phase behavior and rheology of oil-swollen micellar cubic phase and gel emulsions
      in nonionic surfactant systems.
AB  - We have studied the phase behavior and rheological property of the cubic phase
      and related gel emulsions in water/nonionic/dodecane systems. In the phase
      behavior study, it is pointed out that the formation of the discontinuous cubic
      phase (I(1)) is not common in all nonionic surfactant systems; however, a cubic
      phase (I(1)) with oil-swollen micelles or a cubic phase microemulsion is found in
      the water/C(16)EO(6)/dodecane system, which can solubilize large amount of oil.
      It was also observed that water/C(16)EO(6)/dodecane system forms stable gel
      emulsion. In the rheological study we have found an anomalous behavior of the
      I(1) phase in the water/C(12)EO(6)/dodecane and the water/C(16)EO(6)/dodecane
      systems. In the water/C(12)EO(6)/dodecane system, the viscoelastic nature of the
      I(1) phase has been observed, which is shifted to the elastic nature with the
      addition of dodecane, whereas, highly elastic nature was observed in the
      water/C(16)EO(6)/dodecane system. In both the cases shear-thinning behavior were
      seen. The elastic modulus, G' and complex viscosity, |eta*| of the I(1) phase
      increase with the dodecane concentration in the water/C(12)EO(6)/dodecane system,
      whereas, decreasing trend have been observed in the water/C(16)EO(6)/dodecane
      system. This anomalous behavior is suggested due to the nonspherical shape of
      micelles or polydispersity of the micelles in the water/C(16)EO(6)/dodecane
      system. The rheological behavior of the O/I(1) gel emulsion was also studied in
      both the systems.

PMID- 19846108
TI  - 12-Hydroxystearic acid lipid tubes under various experimental conditions.
AB  - There is a growing interest for constructing supramolecular hollow tubes from
      amphiphilic molecules. Aqueous solutions of the ethanolamine salt of 12
      hydroxystearic acid are known to form tubes of several tens of micrometers in
      length with a temperature-tunable diameter. However, the phase behavior of this
      system has not been fully studied. Herein, we report the variation of various
      physico-chemical parameters on the self-assembling properties of this system. The
      effects of the ionic strength, ethanol, doping with other lipids, pH,
      concentration, and the fatty acid/ethanolamine molar ratio R were investigated by
      both phase-contrast microscopy and DSC. We observed the formation of tubes in a
      wide range of parameters. For instance, the molar ratio R can be modified from
      2/3 to 5/2 without altering the formation of tubes. In some but not all cases,
      the tube diameter still varied with temperature. These findings show that tubes
      form under various experimental conditions. This should increase the interest in
      producing such self-assemblies from low-cost fatty acids.

PMID- 19846109
TI  - Ultrasonographic patterns of reproductive organs in infants fed soy formula:
      comparisons to infants fed breast milk and milk formula.
AB  - OBJECTIVE: To determine if differences exist in hormone-sensitive organ size
      between infants who were fed soy formula (SF), milk formula (MF), or breast milk
      (BF). STUDY DESIGN: Breast buds, uterus, ovaries, prostate, and testicular
      volumes were assessed by ultrasonography in 40 BF, 41 MF, and 39 SF infants at
      age 4 months. RESULTS: There were no significant feeding group effects in
      anthropometric or body composition. Among girls, there were no feeding group
      differences in breast bud or uterine volume. MF infants had greater (P < .05)
      mean ovarian volume and greater (P < .01) numbers of ovarian cysts per ovary than
      did BF infants. Among boys, there were no feeding group differences in prostate
      or breast bud volumes. Mean testicular volume did not differ between SF and MF
      boys, but both formula-fed groups had lower volumes than BF infants. CONCLUSIONS:
      Our data do not support major diet-related differences in reproductive organ size
      as measured by ultrasound in infants at age 4 months, although there is some
      evidence that ovarian development may be advanced in MF-fed infants and that
      testicular development may be slower in both MF and SF infants as compared with
      BF. There was no evidence that feeding SF exerts any estrogenic effects on
      reproductive organs studied.

PMID- 19846110
TI  - Cross-sectional analysis of health-related quality of life in pediatric liver
      transplant recipients.
AB  - OBJECTIVE: To investigate the distribution of health-related quality of life in
      pediatric liver transplant recipients compared with a normative population. STUDY
      DESIGN: This cross-sectional, multicenter study was conducted at select centers.
      Patients between 2 and 18 years of age, surviving liver transplantation by at
      least 12 months, were eligible. Parent/guardian fluency in English or Spanish was
      required. Children > or =8 years and parents of all children completed the age
      appropriate versions of the PedsQL 4.0 (Mapi Research Institute, Lyon, France).
      Scores were compared with a sample of healthy children (n = 3911) matched by age
      group, sex, and race/ethnicity and with a sample of pediatric patients with
      cancer receiving chemotherapy and/or radiation. RESULTS: Participants included
      65% (873/1339) of eligible patients. Mean age was 8.17 +/- 4.43 years, and 55%
      were female. The total and subscale scores of PedsQL 4.0 were lower than in
      healthy children (P < .001), with effect sizes for self-report ranging from -0.25
      for Emotional Functioning to -0.68 for School Functioning. Patients and their
      parents reported better physical functioning than patients with cancer but
      similar social and school functioning. Correlations between parent and self
      reports were in the moderate agreement range. CONCLUSIONS: Pediatric liver
      transplant recipients and their parents report lower health-related quality of
      life than control subjects with some domains equal to children receiving cancer
      therapy.

PMID- 19846111
TI  - Favorable outcome of juvenile dermatomyositis treated without systemic
      corticosteroids.
AB  - OBJECTIVE: To describe the course of patients with juvenile dermatomyositis (JDM)
      treated effectively without systemic corticosteroids. STUDY DESIGN: A
      retrospective study of 38 patients with JDM treated at a tertiary care children's
      hospital identified 8 patients who had never received corticosteroids. Disease
      presentation and course, pharmacologic, and ancillary treatments were recorded.
      RESULTS: Patients in the no corticosteroid group were followed for a median of
      2.8 years (range, 2.1 to 9.5 years). Treatment was primarily with intravenous
      immunoglobulin (IVIG) (75%) and methotrexate (50%), with favorable response in
      all. No serious treatment complications were observed; headaches were reported by
      3 patients receiving IVIG. Two patients had a myositis flare after discontinuing
      all medications for more than 1 year; complete resolution of symptoms was
      observed after either 1 or 2 further doses of IVIG. Two patients had calcinosis
      (at 1 and 9 years of disease); however, no patient had joint contractures, muscle
      atrophy, lipodystrophy, or functional limitations. CONCLUSIONS: Systemic
      corticosteroids can be avoided in a select group of patients with JDM.
      Alternative agents such as methotrexate and IVIG may be prescribed to effectively
      treat JDM and prevent complications.

PMID- 19846112
TI  - Increased auditory startle reflex in children with functional abdominal pain.
AB  - OBJECTIVE: To test the hypothesis that children with abdominal pain-related
      functional gastrointestinal disorders have a general hypersensitivity for sensory
      stimuli. STUDY DESIGN: Auditory startle reflexes were assessed in 20 children
      classified according to Rome III classifications of abdominal pain-related
      functional gastrointestinal disorders (13 irritable bowel syndrome [IBS], 7
      functional abdominal pain syndrome; mean age, 12.4 years; 15 girls) and 23
      control subjects (14 girls; mean age, 12.3 years) using a case-control design.
      The activity of 6 left-sided muscles and the sympathetic skin response were
      obtained by an electromyogram. We presented sudden loud noises to the subjects
      through headphones. RESULTS: Both the combined response of 6 muscles and the
      blink response proved to be significantly increased in patients with abdominal
      pain compared with control subjects. A significant increase of the sympathetic
      skin response was not found. Comorbid anxiety disorders (8 patients with
      abdominal pain) or Rome III subclassification did not significantly affect these
      results. CONCLUSIONS: This study demonstrates an objective hyperresponsivity to
      nongastrointestinal stimuli. Children with abdominal pain-related functional
      gastrointestinal disorders may have a generalized hypersensitivity of the central
      nervous system.

PMID- 19846113
TI  - Permanent pediatric diplomate awareness of and perspectives on maintenance of
      certification.
AB  - OBJECTIVE: Since diplomates of the American Board of Pediatrics with permanent
      certificates will not be required to participate in the Maintenance of
      Certification (MOC) program, we determined the perceptions of permanent
      certificate holders about MOC and their degree of interest in participation.
      STUDY DESIGN: We conducted a 12-item mail survey of 1693 diplomates with
      permanent certificates. Frequency distributions were calculated for all survey
      items. chi(2) statistics were used to explore associations between the variables.
      RESULTS: The response rate was 77.7%. Less than one-third of generalist
      respondents (28%, n = 122) and 13% of subspecialists (n = 63) agreed that they
      would be willing to participate in general pediatrics MOC (P < .0001). However,
      approximately half the subspecialists (48%, n = 221) agreed that they would be
      willing to participate in subspecialty MOC. Approximately three-fourths of
      generalists (79%, n = 354) and subspecialists (74%, n = 338) disagreed that MOC
      is necessary for keeping up-to-date in clinical pediatrics. Few respondents
      believed that parents understand the MOC program. CONCLUSION: A wide range of
      attitudes and perceptions about MOC exists among holders of permanent
      certificates. Concerns about the importance of MOC to parents and the usefulness
      of MOC participation in improving quality of care will need to be addressed.

PMID- 19846115
TI  - Microcirculation in preterm infants: profound effects of patent ductus
      arteriosus.
AB  - OBJECTIVES: To assess potential effects of a hemodynamically significant
      persistent ductus arteriosus (sPDA) in the skin microcirculation in preterm
      neonates. STUDY DESIGN: In 25 patients (<32 weeks of gestation; birth weight
      <1250 g) with sPDA (n = 13) or no significant PDA (non-sPDA; n = 12) functional
      vessel density and vessel diameters were investigated prospectively. Sidestream
      dark field imaging was performed in the skin of both arms from the third day of
      life until PDA closure or until day 7 or 8 for the non-sPDA group. RESULTS:
      Before PDA treatment, functional vessel density was significantly lower in the
      sPDA group compared with the non-sPDA group. In the sPDA group, there were
      significantly fewer large vessels (diameter >20 microm) and significantly more
      small vessels (diameter <10 microm). After successful PDA treatment, these
      differences disappeared. In both groups, functional vessel density differed
      significantly between the left and right arm, persisting even after successful
      treatment. Regression analysis showed an inverse linear correlation between the
      hemodynamic echocardiographic findings and functional vessel density (P <.005).
      CONCLUSION: sPDA causes major changes in the microcirculation of premature
      neonates; functional vessel density is reduced, with a shift in perfusion from
      larger toward smaller vessels. The redistribution of flow might be a compensatory
      mechanism to preserve physiologic metabolism.

PMID- 19846114
TI  - High-intensity training increases spontaneous physical activity in children: a
      randomized controlled study.
AB  - OBJECTIVE: To test the hypothesis that resistance training may increase
      spontaneous physical activity in children. STUDY DESIGN: Two junior ice hockey
      teams were randomly assigned to unchanged training schedules (team ZSC, 21 boys;
      mean age, 13.2 years) or to participate twice weekly in guided resistance
      training for 4 months (team GCK, 25 boys; mean age, 13.4 years). Spontaneous
      physical activity energy expenditure (SpAEE; 3-axial accelerometry for 7 days),
      muscle strength, and body composition (dual energy x-ray absorptiometry) were
      measured at 0, 4, and 12 months. RESULTS: Baseline measures did not differ in the
      groups, except for higher leg and trunk strength in team ZSC. In the intervention
      group compared with the control group, SpAEE significantly (P < or = .02)
      increased at 4 months (+25.5% versus 0%) and 12 months (+13.5% versus -9.5%). Leg
      and arm strength increased because of training intervention; all other variables
      were unchanged. None of these variables correlated with changes in SpAEE.
      CONCLUSION: In boys who play ice hockey, spontaneous physical activity is
      inducible with resistance training; this effect seems to be independent of
      changes in body composition and strength. If this was confirmed in unselected
      children, resistance training might be a new strategy for childhood obesity
      prevention programs.

PMID- 19846116
TI  - Long-term clinical significance of thyroid autoimmunity in children with celiac
      disease.
AB  - OBJECTIVE: To evaluate the long-term outcome of thyroid function and autoimmunity
      in a large series of children with celiac disease. STUDY DESIGN: This
      longitudinal, retrospective study (duration of follow-up, 8.9 +/- 4.0 years) was
      conducted at the Pediatric Department, University of Bologna, Italy. One hundred
      thirty-five consecutive patients diagnosed between June 1990 and December 2004
      and followed on a gluten-free diet were examined. Inclusion criteria were good
      dietary compliance and duration of follow-up for at least 3 years. RESULTS: Of
      101 patients who never showed positive antithyroid titers during the follow-up,
      86 remained euthyroid; 15 showed high thyroid-stimulating hormone values at
      diagnosis that normalized in 11 cases after 12 to 18 months of gluten withdrawal.
      Of 31 patients with persistently positive antibody titers, 23 (74%) remained
      consistently euthyroid during the follow-up and 8 (26%) had a subclinical
      hypothyroidism. The prevalence of cases with positive antibodies was similar in
      children with growth retardation or gastroenterological symptoms at diagnosis and
      different durations of gluten exposure. CONCLUSIONS: The presence of antithyroid
      antibodies in children with celiac disease has a low predictive value for the
      development of thyroid hypofunction during the indicated surveillance period.
      Longer follow-up is needed.

PMID- 19846117
TI  - Cardiovascular abnormalities, interventions, and long-term outcomes in infantile
      Williams syndrome.
AB  - OBJECTIVE: To determine the prevalence of cardiovascular abnormalities (CVA) and
      outcomes in patients with Williams syndrome presenting before 1 year of age.
      STUDY DESIGN: A retrospective review was undertaken of consecutive patients with
      WS at our institution from January 1, 1980, through December 31, 2007. WS was
      diagnosed by an experienced medical geneticist and/or by fluorescence in situ
      hybridization. CVA were diagnosed with the use of echocardiography, cardiac
      catheterization, or computerized tomographic angiography. Freedom from
      intervention was determined using Kaplan-Meier analysis. RESULTS: The study group
      was 129 patients with CVA. Age at presentation was 127 +/- 116 days, with follow
      up of 8.0 +/- 7.5 years (0 to 42 years). The most common lesions were peripheral
      pulmonary artery stenosis (62%) and supravalvar aortic stenosis (57%). Other CVA
      were common. CV interventions were performed in 29%, with 58% of those before 1
      year. Freedom from intervention was 85%, 73%, and 66% at 1, 5, and 25 years,
      respectively. Four patients died. CONCLUSIONS: CVA are the most common
      manifestations of infantile Williams syndrome and occur with greater frequency
      than previously reported. In those with CVA, interventions are common and usually
      occur by 5 years of age. Most of these patients do not require intervention on
      long-term follow-up, and overall mortality is low.

PMID- 19846118
TI  - Aberrant REST-mediated transcriptional regulation in major depressive disorder.
AB  - There is growing evidence that aberrant transcriptional regulation is one of the
      key components of the pathophysiology of mood disorders. The repressor element-1
      silencing transcription factor (REST) is a negative regulator of genes that
      contain the repressor element-1 (RE-1) binding site. REST has many target genes,
      including corticotropin releasing hormone (CRH), brain-derived neurotrophic
      factor, serotonin 1A receptor, which are suggested to be involved in the
      pathophysiology of depression and the action of antidepressants. However, a
      potential role for REST-mediated transcriptional regulation in mood disorders
      remains unclear. In this study, we examined the mRNA levels of REST and its known
      and putative target genes, using quantitative real-time PCR in peripheral blood
      cells of patients with major depressive and bipolar disorders in both a current
      depressive and a remissive state. We found reduced mRNA expression of REST and
      increased mRNA expression of CRH, adenylate cyclase 5, and the tumor necrosis
      factor superfamily, member 12-13 in patients with major depressive disorder in a
      current depressive state, but not in a remissive state. Altered expression of
      these mRNAs was not found in patients with bipolar disorder. Our results suggest
      that the aberrant REST-mediated transcriptional regulation of, at least, CRH,
      adenylate cyclase 5, and tumor necrosis factor superfamily, member 12-13, might
      be state-dependent and associated with the pathophysiology of major depression.

PMID- 19846119
TI  - Clinical manifestations, diagnostic criteria and therapy of Hashimoto's
      encephalopathy: report of two cases.
AB  - Hashimoto's encephalopathy (HE) is a rare, still not well understood, autoimmune
      disease with neurological and psychiatric manifestations. and elevated titers of
      antithyroid antibodies in serum and cerebrospinal fluid (CSF) as a hallmark of
      the disease. Patients are mostly women. Current diagnostic criteria include
      corticosteroide responsiveness, but it is the case in only 50% of patients with
      HE. In steroid non-responders other immunomodulatory therapies or plasmapheresis
      could be applied. Disease course can be acute, subacute, chronic or relapsing
      remitting. Two distinct forms emerged from the reported cases: a vasculitic type
      characterized by multiple relapsing-remitting stroke-like episodes and mild
      cognitive impairment and a diffuse progressive type characterized by dementia and
      psychiatric symptoms. Both forms may be accompanied by depressed level of
      consciousness (stupor or coma), tremor, seizures, or myoclonus. We present two
      patients with two distinct forms of HE who had different clinical manifestations
      and response to therapy.

PMID- 19846120
TI  - Combination of myotonic dystrophy and hereditary motor and sensory neuropathy.
AB  - Myotonic Dystrophy Type 1 (DM1) in combination with demyelinating neuropathy is
      very rare in literature. In this study, DM1 and demyelinating neuropathy were
      demonstrated clinically and electromyographically in a 43-year-old female patient
      from Turkey. In the patient an expanded CTG repeat in the Myotonic Dystrophy
      Protein Kinase (DMPK) gene was confirmed in combination with a duplication in the
      Charcot-Marie-Tooth Disease (CMT1A) gene. DM1 was also determined in her 25-year
      old son.

PMID- 19846121
TI  - Unifocalization of major aortopulmonary collateral arteries in pulmonary atresia
      with ventricular septal defect is essential to achieve excellent outcomes
      irrespective of native pulmonary artery morphology.
AB  - OBJECTIVE: Pulmonary atresia with ventricular septal defect and major
      aortopulmonary collateral arteries is a complex lesion with a high rate of
      natural attrition. We evaluated the outcomes of our strategy of unifocalization
      in the management of these patients. METHODS: From 1989 to 2008, 216 patients
      entered a pathway aiming for complete repair by unifocalizing major
      aortopulmonary arteries to a right ventricle-pulmonary artery conduit with
      ventricular septal defect closure. Where ventricular septation was not possible,
      definitive repair was considered to include pulmonary artery reconstruction and a
      right ventricle-pulmonary artery conduit or systemic shunt. Native pulmonary
      artery morphology was classified into confluent intrapericardial (n = 139),
      confluent intrapulmonary (n = 51), and nonconfluent intrapulmonary (n = 26).
      RESULTS: A total of 203 patients (85%) had definitive repair at a median age of
      2.0 years. There was no statistically significant difference in survival after
      complete repair among the 3 morphologic pulmonary artery groups (P = .18). A
      total of 132 patients (56%) had complete repair with ventricular septal defect
      closure, as a single procedure in 111 patients and a staged procedure in 21
      patients. Focalization of major aortopulmonary collateral arteries with proven
      long-term patency with the right ventricle was associated with a survival benefit
      compared with 14 patients in whom unifocalization was not possible and who had
      only systemic shunts. Overall survival was 89% at 3 years after definitive
      repair. During follow-up, 190 patients required 196 catheter reinterventions and
      60 surgical reinterventions. CONCLUSION: By using a strategy of unifocalization,
      intrapericardial pulmonary artery reconstruction, and right ventricle-pulmonary
      artery conduit, excellent long-term survival can be achieved in this group of
      patients even in the absence of native intrapericardial pulmonary arteries.

PMID- 19846123
TI  - The Ross-Yacoub procedure for aneurysmal autograft roots: a strategy to preserve
      autologous pulmonary valves.
AB  - OBJECTIVES: Autograft dilatation is leading to an increase in root reoperations
      late after the Ross procedure. A 14-year clinical experience was reviewed to
      define the feasibility and outcome of the autograft valve-sparing root
      reoperation. METHODS: One hundred twenty-six patients surviving an average of 7.4
      +/- 9.9 years after the Ross procedure underwent cross-sectional clinical and
      echocardiographic examination. Study end points were freedom from autograft
      dilatation (diameter >4 cm or 2.1 cm/m(2)), root reoperation, root replacement,
      and functional outcome after the valve-sparing reoperation. RESULTS: Thirty-one
      (25%) patients had dilatation, with 45% +/- 9% freedom at 14 years. In 14 (11%)
      patients an autograft aneurysm (>5.0 cm) was found: 12 had reoperations at 8.9 +/
      2.6 years after the Ross procedure. Risk factors for root reoperation at
      multivariate analysis were root technique (P = .01), root dilatation (P = .001),
      and follow-up duration (P = .06). Two patients had root replacement, and 10 (83%)
      had remodeling with valve preservation (8 Yacoub procedures and 2 sinotubular
      junction/ascending aorta procedures); all survived reoperation. Absence of severe
      autograft insufficiency (P = .04) and convergent-type aneurysm (P = .05) were
      associated with successful valve preservation. Fourteen-year freedom from root
      reoperation was 80% +/- 7%, and freedom from full root replacement was 97% +/-
      4%. At 3.2 +/- 1.5 years (range, 0.2-4.8 years) after root reoperation, all
      patients are in New York Heart Association class I and are medication free: 9 of
      10 patients have mild autograft valve insufficiency or less, and 1 required valve
      replacement 51 months after remodeling. One patient carried out 2 uncomplicated
      pregnancies 3 and 4 years after the Ross-Yacoub procedure. CONCLUSIONS: Root
      reoperation with pulmonary valve preservation is feasible in the majority of
      patients with autograft aneurysms, allowing for maintenance of normal quality of
      life. Referral of patients with a dilated root before the appearance of severe
      valve insufficiency increases the likelihood of pulmonary valve sparing.
      Functional behavior of remodeled autograft roots is rewarding; however, continued
      observation is warranted.

PMID- 19846124
TI  - Transcatheter aortic valve implantation for high-risk patients with severe aortic
      stenosis: A systematic review.
AB  - OBJECTIVES: The present systematic review objectively assessed the safety and
      clinical effectiveness of transcatheter aortic valve implantation for patients at
      high surgical risk with severe aortic stenosis. METHODS: Electronic searches were
      performed in 6 databases from January 2000 to March 2009. The end points included
      feasibility, safety, efficacy, and durability. Clinical effectiveness was
      synthesized through a narrative review with full tabulation of results of all
      included studies. RESULTS: The current evidence on transcatheter aortic valve
      implantation for aortic stenosis is limited to short-term observational studies.
      The overall procedural success rates ranged from 74% to 100%. The incidence of
      major adverse events included 30-day mortality (0%-25%), major ventricular
      tachyarrhythmia (0%-4%), myocardial infarction (0%-15%), cardiac tamponade (2%
      10%), stroke (0%-10%), conversion to surgery (0%-8%), moderate to major
      paravalvular leak (4%-35%), vascular complication (8%-17%), valve-in-valve
      procedure (2%-12%), and aortic dissection/perforation (0%-4%). The overall 30-day
      major adverse cardiovascular and cerebral events ranged from 3% to 35%. The mean
      aortic valve area ranged from 0.5 to 0.8 cm(2) before and 1.3 to 2.0 cm(2) after
      transcatheter aortic valve implantation. The mean pressure gradient ranged from
      34 to 58 mm Hg before and 3 to 12 mm Hg after transcatheter aortic valve
      implantation. There was no significant deterioration in echocardiography
      measurements during the assessment period. Death rate at 6 months postprocedure
      ranged from 18% to 48%. No studies had adequate follow-up to reliably evaluate
      long-term outcomes. CONCLUSIONS: The procedure has a potential for serious
      complications. Although short-term efficacy based on echocardiography
      measurements is good, there is little evidence on long-term outcomes. The use of
      transcatheter aortic valve implantation should be considered only within the
      boundaries of clinical trials.

PMID- 19846125
TI  - Simulation in coronary artery anastomosis early in cardiothoracic surgical
      residency training: the Boot Camp experience.
AB  - OBJECTIVE: We evaluated focused training in coronary artery anastomosis with a
      porcine heart model and portable task station. METHODS: At "Boot Camp," 33 first
      year cardiothoracic surgical residents participated in 4-hour coronary
      anastomosis sessions (6-7 attending surgeons per group of 8-9 residents). At
      beginning, midpoint, and session end, anastomosis components were assessed on a 3
      point rating scale (1 good, 2 average, 3 below average). Performances were video
      recorded and reviewed by 3 surgeons in a blinded fashion. Participants completed
      questionnaires at session end, with follow-up surveys at 6 months. RESULTS: Ten
      to 18 end-to-side anastomoses with porcine model and task station were performed.
      Initial assessments ranged from 2.11 +/- 0.58 (forceps use) to 2.44 +/- 0.48
      (needle angles). Midpoint scores ranged from 1.76 +/- 0.63 (forceps use) to 1.91
      +/- 0.49 (needle angles). Session end scores ranged from 1.29 +/- 0.45 (needle
      holder use) to 1.58 +/- 0.50 (needle transfer and suture management and tension;
      P < .001). Video recordings confirmed improved performance (interrater
      reliability >0.5). All respondents agreed that task station and porcine model
      were good methods of training. At 6 months, respondents noted that the
      anastomosis session provided a basis for training; however, only slightly more
      than half continued to practice outside the operating room. CONCLUSIONS: Four
      hour focused training with porcine model and task station resulted in improved
      ability to perform anastomoses. Boot Camp may be useful in preparing residents
      for coronary anastomosis in the clinical setting, but emphasis on simulation
      development and deliberate practice is necessary.

PMID- 19846126
TI  - Re: Peak retrograde flow: a novel predictor of persistent, progressive and new
      onset asymmetry in adolescent varicocele. K. A. Kozakowski, C. K. Gjertson, G. J.
      Decastro, S. Poon, A. Gasalberti and K. I. Glassberg. J Urol 2009; 181: 2717
      2723.

PMID- 19846128
TI  - Re: Presence of tumor necrosis is not a significant predictor of survival in
      clear cell renal cell carcinoma: higher prognostic accuracy of extent based
      rather than presence/absence classification. T. Klatte, J. W. Said, M. de
      Martino, J. Larochelle, B. Shuch, J. Y. Rao, G. V. Thomas, F. F. Kabbinavar, A.
      S. Belldegrun and A. J. Pantuck. J Urol 2009; 181: 1558-1564.

PMID- 19846129
TI  - Re: Benign prostatic obstruction and Parkinson's disease--should transurethral
      resection of the prostate be avoided? B. Roth, U. E. Studer, C. J. Fowler and T.
      M. Kessler. J Urol 2009; 181: 2209-2213.

PMID- 19846130
TI  - Obesity and benign prostatic hyperplasia: clinical connections, emerging
      etiological paradigms and future directions.
AB  - PURPOSE: Benign prostatic hyperplasia is a highly prevalent disease in older men
      with substantial adverse effects on public health. Classic etiological paradigms
      for benign prostatic hyperplasia focus on nonmodifiable risk factors. However,
      obesity also potentially promotes benign prostatic hyperplasia. MATERIALS AND
      METHODS: We performed a structured, comprehensive literature review to identify
      studies of obesity, benign prostatic hyperplasia, lower urinary tract symptoms
      and physical activity. RESULTS: A preponderance of published evidence suggests
      strong positive associations of obesity with benign prostatic hyperplasia and
      lower urinary tract symptoms. This evidence encompasses most established metrics
      of adiposity, including body mass index, waist circumference and waist-to-hip
      ratio, and falls under 3 general categories, including prostate volume, clinical
      benign prostatic hyperplasia and lower urinary tract symptoms. 1) Prior studies
      consistently showed that increased adiposity is positively associated with
      radiographically determined prostate volume and enlargement, suggesting that
      obesity promotes prostate growth. 2) Most studies revealed that obesity increases
      the risk of clinical benign prostatic hyperplasia by several measures, including
      the initiation of benign prostatic hyperplasia medical treatment, noncancer
      prostate surgery, physician diagnosed benign prostatic hyperplasia, histological
      diagnosis and urinary flow rate. 3) Prior studies demonstrated that obesity
      increases the risk of lower urinary tract symptoms, as measured by a validated
      questionnaire. Also, most studies showed that physical activity significantly
      decreases the risk of benign prostatic hyperplasia. CONCLUSIONS: Obesity markedly
      increases the risk of benign prostatic hyperplasia. Since physical activity
      decreases the risk of benign prostatic hyperplasia, these observations support
      the development of novel prevention strategies and treatment targeted toward
      adiposity, weight loss and lifestyle.

PMID- 19846131
TI  - Impact of diabetes and obesity on the prostate and urethra: implications to
      improved bladder dysfunction understanding and treatment.
AB  - PURPOSE: Alterations in bladder function are well documented in response to
      diabetes and obesity. Nonetheless, clinical manifestations of bladder dysfunction
      are diverse and the efficacy of available therapy is suboptimal. Since the
      bladder is only 1 component of the lower urinary tract, we explored existing
      evidence for the potential contribution(s) of other major lower urinary tract
      structures to diabetes and obesity related bladder dysfunction, namely the
      prostate and the urethra. MATERIALS AND METHODS: We performed a MEDLINE database
      search of the relevant literature. RESULTS: A relatively large literature exists
      on bladder dysfunction and the urethra. However, when additional search terms
      were added, such as prostate, diabetes and obesity, there was a dramatic decrease
      in the number of retrieved citations. These observations are consistent with the
      vanishingly small available literature on the impact of diabetes on prostatic
      biology and urethral function, and their potential impact on bladder
      physiology/dysfunction. The available literature documents significant
      alterations in prostatic biology and urethral function in the setting of diabetes
      and/or obesity. CONCLUSIONS: The observed diversity in diabetes and obesity
      related bladder dysfunction, and the variable efficacy of currently available
      treatments may be related at least in part to the differential impact of these
      disease states on the complex integration of bladder function with other
      structural components of the lower urinary tract, namely the urethra and the
      prostate. More comprehensive investigations of this system should lead to
      improved understanding of the mechanistic basis for the observed pathophysiology
      and identify novel treatment regimens.

PMID- 19846132
TI  - Urological complications of obesity and diabetes.

PMID- 19846133
TI  - Obesity and urinary incontinence: epidemiology and clinical research update.
AB  - PURPOSE: We reviewed the epidemiological literature on the association of obesity
      and urinary incontinence, and summarized clinical trial data on the effect of
      weight loss on urinary incontinence. MATERIALS AND METHODS: We systematically
      searched for published community based prevalence studies with bivariate or
      multivariate analysis of the association of urinary incontinence and
      overweight/obesity in women. Case series and randomized controlled trials of the
      effect of surgical, behavioral and pharmacological weight loss on urinary
      incontinence are summarized. RESULTS: Epidemiological studies showed that obesity
      is a strong independent risk factor for prevalent and incident urinary
      incontinence. There was a clear dose-response effect of weight on urinary
      incontinence with each 5-unit increase in body mass index associated with about a
      20% to 70% increase in the urinary incontinence risk, and the maximum effect of
      weight rarely exceeded an OR of greater than 4 to 5 on well controlled analyses.
      The odds of incident urinary incontinence during 5 to 10 years increased by
      approximately 30% to 60% for each 5-unit increase in body mass index. There may
      be a stronger association of increasing weight with prevalent and incident stress
      incontinence, including mixed incontinence, than with urge incontinence and
      overactive bladder syndrome. Weight loss studies indicated that surgical and
      nonsurgical weight loss led to significant improvements in urinary incontinence
      symptoms. CONCLUSIONS: Epidemiological studies document overweight and obesity as
      important risk factors for urinary incontinence. Weight loss by surgical and more
      conservative approaches is effective to decrease urinary incontinence symptoms
      and should be strongly considered a first line treatment in this patient
      population.

PMID- 19846134
TI  - Diabetes mellitus and urinary tract infection: epidemiology, pathogenesis and
      proposed studies in animal models.
AB  - PURPOSE: We reviewed the current state of knowledge about urinary tract infection
      in patients with diabetes from the clinical and basic science perspectives. We
      identified key knowledge gaps and areas for further research. MATERIALS AND
      METHODS: We performed a focused literature search on certain topics, including
      clinical studies related to etiology and pathophysiology of urinary tract
      infection in patients with diabetes, urinary tract infection studies in animal
      models of diabetes and basic science studies of the molecular mechanisms of
      urinary tract infection. RESULTS: Individuals with diabetes are at higher risk
      for urinary tract infection. Increased susceptibility in patients with diabetes
      is positively associated with increased duration and severity of diabetes.
      Clinical epidemiological data identifying mechanisms of increased urinary tract
      infection susceptibility in patients with diabetes are generally lacking and
      indicate only that urinary tract infections in women with and without diabetes
      are qualitatively similar in bacterial etiology and morbid sequelae. Existing
      animal models for diabetes have not been well characterized for urinary tract
      infection research. The increased incidence, prevalence and severity of urinary
      tract infection in patients with diabetes argue for aggressive antibacterial
      chemotherapy but novel therapies resulting from urinary tract infection research
      in nondiabetic animal models are still not available. CONCLUSIONS: Future
      clinical investigations of urinary tract infection in patients with diabetes
      should focus on how the disease differs from that in patients without diabetes,
      notably on the role of glycosuria and urinary tract infection risk. Basic science
      research priorities for urinary tract infection in patients with diabetes should
      emphasize further development of diabetic animal models for urinary tract
      infection research and clinical translation of known important virulence
      determinants into new therapies.

PMID- 19846135
TI  - Clinical research in diabetes and urinary incontinence: what we know and need to
      know.
AB  - PURPOSE: We discuss epidemiological and clinical trial research in women with
      urinary incontinence and diabetes, and provide directions for future research.
      MATERIALS AND METHODS: Published epidemiological and clinical trial literature
      examining diabetes and incontinence is presented. RESULTS: Multiple studies have
      now confirmed that the prevalence and incidence of incontinence is increased in
      women with type 2 diabetes. Emerging evidence also suggests higher incontinence
      rates in women with type 1 diabetes or prediabetes. Clinical trial research
      suggests that weight loss can decrease incontinence in women with prediabetes. An
      ongoing multicenter trial will examine the effects of weight loss on incontinence
      in women with type 2 diabetes. Limited trial data in those with type 1 diabetes
      suggest that intensive glycemic control does not appear to decrease the long-term
      risk of incontinence in women with type 1 diabetes. CONCLUSIONS: Future research
      is needed to identify the risk factors, mechanisms, and most effective treatment
      and prevention strategies to decrease urinary incontinence in women with type 1
      or 2 diabetes, or prediabetes. Physicians should be alert for urinary
      incontinence because it is often not reported and, therefore, it is under treated
      in women with diabetes and prediabetes.

PMID- 19846136
TI  - Diabetes, obesity and erectile dysfunction: field overview and research
      priorities.
AB  - PURPOSE: We provide an overview of basic, clinical and epidemiological research
      in the field of erectile dysfunction and important research priorities presented
      at the 2009 National Institute of Diabetes and Digestive and Kidney Diseases
      symposium on Urological Complications of Diabetes and Obesity. MATERIALS AND
      METHODS: Experts in molecular biology, physiology, pharmacology, clinical trials,
      epidemiology and urological surgery highlighted current knowledge on erectile
      dysfunction associated with diabetes mellitus and obesity. RESULTS: Predictable
      associations between erectile dysfunction, and poor diabetic control and
      modifiable risk factors, including body mass index, have not yet been translated
      into randomized trials in the United States. The relationship between erectile
      dysfunction and metabolic syndrome, and surrogate markers for erectile
      dysfunction requires further investigation. Basic research aimed at discovering
      disease mechanisms and therapeutic targets has focused on autonomic neuropathy,
      vascular dysfunction, smooth muscle contractile function and matrix. However,
      significant gaps exist in regard to the integration of molecular, cellular and
      functional data. Animal models of type 2 diabetes and obesity associated erectile
      dysfunction require investigation because most basic science studies have used
      rodent models of type 1 diabetes. CONCLUSIONS: Studies are needed to synthesize a
      systems biology understanding of erectile function/dysfunction, and characterize
      and disseminate rodent models of erectile dysfunction associated with type 2
      diabetes and obesity. Clinical studies are needed of promising intervention and
      prevention strategies. Leveraging existing and future cohort phenotypes, and
      biological samples is needed for risk factor analysis, biomarker discovery and
      genome wide association studies.

PMID- 19846137
TI  - Diabetic bladder dysfunction: current translational knowledge.
AB  - PURPOSE: Diabetes mellitus, a metabolic disorder caused by an absolute or
      relative deficiency of insulin, is a debilitating and costly disease with
      multiple serious complications. Lower urinary tract complications are among the
      most common complications of diabetes mellitus. The most common, bothersome lower
      urinary tract complication of diabetes mellitus is diabetic cystopathy or
      diabetic bladder dysfunction. We reviewed the current translational knowledge of
      diabetic bladder dysfunction. MATERIALS AND METHODS: We performed a search of the
      English literature through PubMed. The key words used were diabetes and bladder
      dysfunction or cystopathy. Our data and perspective are provided for
      consideration of the future direction of research. RESULTS: Despite traditional
      recognition of diabetic bladder dysfunction as a voiding problem characterized by
      poor emptying and overflow incontinence, recent clinical and experimental
      evidence indicate storage problems such as urgency and urge incontinence in
      diabetes mellitus cases. Recent experimental evidence from studies of diabetic
      bladder dysfunction in small animal models of diabetes mellitus show a temporal
      effect on diabetic bladder dysfunction. Early phase diabetes mellitus causes
      compensated bladder function and the late phase causes decompensated bladder
      function. The temporal theory could plausibly provide the scientific road map to
      correlate clinical and experimental findings, and identify the role of mechanisms
      such as polyuria, hyperglycemia, oxidative stress, autonomic neuropathy and
      decompensation of the bladder contractile apparatus in the creation of clinical
      and experimental manifestations of diabetic bladder dysfunction. CONCLUSIONS:
      Diabetic bladder dysfunction includes time dependent manifestations of storage
      and emptying problems. Identifying mechanistic pathways would lead to the
      identification of therapeutic intervention.

PMID- 19846138
TI  - Evening primrose oil supplementation increases citraturia and decreases other
      urinary risk factors for calcium oxalate urolithiasis.
AB  - PURPOSE: We investigated the effects of gamma-linolenic acid (an omega-6
      polyunsaturated fatty acid) in the form of evening primrose oil on calcium
      oxalate urinary stone risk factors in 2 ethnic groups. MATERIALS AND METHODS:
      Eight black and 8 white healthy male subjects ingested 1,000 mg evening primrose
      oil (Natrodale, Kuils River, South Africa) daily for 20 days while following a
      free diet. Arachidonic acid content was determined by a dietary questionnaire. On
      days 0, 10 and 20, and 4 days after protocol 24-hour urine samples were
      collected. Samples were analyzed using routine assays. RESULTS: Citraturia
      increased significantly in each group. Urinary oxalate showed a tendency to
      decrease in black subjects. Calciuria and the Tiselius risk index decreased
      significantly in each group. Carryover effects were observed. CONCLUSIONS: To our
      knowledge increased citraturia has not been previously reported for any essential
      fatty acid. We hypothesize that evening primrose oil inhibits lipogenesis,
      thereby decreasing citrate consumption. For the decrease in oxaluria we suggest
      that evening primrose oil alters membrane fatty acid composition, thereby
      inhibiting the modulation of protein kinases that lead to hyperoxaluria. In
      regard to decreased calciuria we suggest that evening primrose oil modulates
      delta-5 and/or delta-6-desaturase, thereby inhibiting the production of
      arachidonic acid and prostaglandin E2, which influence calciuria. The different
      response in the 2 groups with respect to oxaluria confirms previously reported
      differences in sensitivity toward supplemental ingestion. Data suggest that
      evening primrose oil supplementation should be investigated as a possible
      conservative treatment for calcium oxalate urolithiasis.

PMID- 19846139
TI  - Polymorphisms in tumor necrosis factor-A gene and prostate cancer risk in North
      Indian cohort.
AB  - PURPOSE: The proinflammatory cytokine tumor necrosis factor-alpha has an
      important role in the pathogenesis of prostate cancer. Single nucleotide
      polymorphisms in the promoter region of the TNF-A gene alter tumor necrosis
      factor-alpha transcription. Thus, we studied the association of 4 SNPs in the
      promoter region of TNF-A gene, including -1031T>C, -863C>A, -857 C>T and -308
      G>A, in a North Indian cohort of patients with prostate cancer. MATERIALS AND
      METHODS: The study involved 453 subjects. All 197 case and 256 control samples
      were genotyped for the 4 promoter polymorphisms in the TNF-A gene using allele
      specific polymerase chain reaction and polymerase chain reaction-restriction
      fragment length polymorphism. RESULTS: Results showed an increased risk of
      prostate cancer for the TNF-A -1031 CC genotype (OR 2.01, p = 0.03). No
      significant association was observed for the TNF-A -863 C>A, TNF-A -857 C>T or 
      308 G>A polymorphisms. Haplotype analysis revealed that TNF-A -1031C-863C-857T
      308G was significantly associated with prostate cancer risk (OR 2.22, p = 0.013).
      Moreover, the TNF-A -1031 C and -857 T alleles were associated with higher tumor
      grade and an increased risk of tumor progression and metastasis. CONCLUSIONS:
      These results show that TNF-A polymorphisms have an important role in prostate
      cancer pathogenesis. Results are in line with findings in other studies from the
      West and to our knowledge for the first time from India indicating the
      involvement of immune system genes in prostate cancer pathogenesis.

PMID- 19846140
TI  - Expression profile of the polycomb group protein enhancer of Zeste homologue 2
      and its prognostic relevance in renal cell carcinoma.
AB  - PURPOSE: EZH2 increases the proliferation rate and apoptosis resistance of renal
      cell carcinoma cell lines. To date its clinical impact on the outcome in patients
      with renal cell carcinoma is not known. To our knowledge this is the first study
      of the association of EZH2 expression with histopathological features and disease
      outcomes in a large cohort of patients who underwent surgery for renal cell
      carcinoma. MATERIALS AND METHODS: Real-time reverse transcriptase-polymerase
      chain reaction was done to quantify EZH2 expression in malignant and adjacent
      benign renal tissue from a cohort of 119 patients with clear cell renal cell
      carcinoma. Median followup was 51 months. Immunohistochemistry was performed in a
      subset of samples. The impact of EZH2 expression on clinicopathological tumor
      features and outcome was investigated. RESULTS: EZH2 was over expressed in renal
      cell carcinoma compared to adjacent benign renal parenchyma (median 57.02, range
      0 to 368.11 vs 0, range 0 to 280.87, p <0.001). Immunohistochemistry showed
      concordant results and revealed EZH2 protein predominantly located in the
      nucleus. EZH2 expression was not associated with histopathological tumor features
      and patient characteristics. High EZH2 levels predicted a lower disease
      recurrence rate on univariate and multivariate analysis (p = 0.047 and 0.037,
      respectively). CONCLUSIONS: These data support a role of EZH2 expression for
      renal cell carcinoma tumorigenesis rather than tumor progression. Contrary to
      previous EZH2 findings in cases of various human malignancies, high tumor EZH2
      levels appear to indicate less aggressive tumor phenotypes with a favorable
      prognosis in renal cell carcinoma cases. Our findings suggest that EZH2 provides
      not only a potential therapeutic target, but also a molecular parameter for
      outcome prediction in patients with renal cell carcinoma.

PMID- 19846141
TI  - Unilateral ureteral obstruction alters expression of acid-base transporters in
      rat kidney.
AB  - PURPOSE: Unilateral ureteral obstruction is a common clinical problem that is
      often associated with a urinary acidification defect caused by decreased net H(+)
      secretion and/or HCO(3)(-) reabsorption. To clarify the molecular mechanisms of
      these defects we examined expression levels of key acid-base transporters along
      the renal nephron segments and collecting duct. MATERIALS AND METHODS: Wistar
      rats (Mollegard Breeding Centre, Eiby, Denmark) underwent 24-hour unilateral
      ureteral obstruction, unilateral ureteral obstruction release followed for 4 days
      or unilateral ureteral obstruction release followed for 4 days plus experimental
      acidosis induced by NH(4)Cl oral administration. After sacrifice kidneys were
      processed for immunoblotting and immunohistochemistry. RESULTS: Semiquantitative
      immunoblotting revealed that unilateral ureteral obstruction caused significant
      mean +/- SE down-regulation of type 3 Na(+)/H(+) exchanger to 53% +/- 9%,
      electrogenic Na(+)/HCO(3)(-) cotransporter to 60% +/- 9%, type 1 bumetanide
      sensitive Na(+)-K(+)(NH(4)(+)) -2Cl(-) cotransporter to 64% +/- 7%,
      electroneutral Na(+)/HCO(3)(-) cotransporter to 43% +/- 4% and anion exchanger
      (pendrin) to 53% +/- 10% in the obstructed kidney, which was confirmed by
      immunohistochemistry. After release of unilateral ureteral obstruction down
      regulation of these transporters persisted together with marked down-regulation
      of H(+)-adenosine triphosphatase in the obstructed kidney. In rats with
      unilateral ureteral obstruction release followed for 4 days with experimental
      acidosis induced by NH(4)Cl oral administration plasma pH and HCO(3)(-) were
      dramatically decreased in response to NH(4)Cl for 2 days compared with those in
      sham operated rats with acid loading, indicating a defect in H(+) excretion and
      HCO(3)(-) reabsorption after obstruction release. Expression of these
      transporters did not change in the contralateral nonobstructed kidney of rats
      with unilateral ureteral obstruction and unilateral ureteral obstruction release
      followed for 4 days. CONCLUSIONS: The expression of renal acid-base transporters
      is markedly decreased in the obstructed kidney, which may be responsible for the
      contribution of impaired renal H(+) excretion and HCO(3)(-) reabsorption to the
      urinary acidification defect in response to unilateral ureteral obstruction.

PMID- 19846143
TI  - Animal models of diabetic uropathy.
AB  - PURPOSE: Diabetes mellitus is a group of debilitating and costly diseases with
      multiple serious complications. Lower urinary tract complications or diabetic
      uropathy are among the most common complications of diabetes mellitus, surpassing
      widely recognized complications such as neuropathy and nephropathy. Diabetic
      uropathy develops in individuals with types 1 and 2 diabetes, and little is known
      about the natural history of these common and troublesome complications. Animal
      models have the potential to reveal mechanisms and aid in the development of
      treatment strategies. MATERIALS AND METHODS: We present a review of available
      animal models of diabetes mellitus relative to their use in the study of diabetic
      uropathy. RESULTS: Large and small animal models of diabetes mellitus are
      available. While large animals such as dogs and swine may closely mirror the
      human disease in size and phenotype, the time between diabetic complication onset
      and development, and associated husbandry expenditures can make acquiring data on
      statistically valid sample sizes prohibitively expensive. In contrast, small
      animal models (rats and mice) have much lower expenditures for a larger number of
      animals and compressed observation time due to a shorter life span. Also, mice
      are readily manipulated genetically to facilitate the isolation of the effect of
      single genes (transgenic and knockout mice). Type 1 diabetes mellitus can be
      induced chemically with streptozotocin, which is selectively toxic to pancreatic
      beta cells. Type 2 diabetes mellitus models have been developed by selective
      breeding for hyperglycemia with or without associated obesity. Diabetic uropathy
      has been noted in several well characterized, predictable animal models of
      diabetes mellitus. CONCLUSIONS: Diabetic uropathy, including diabetic bladder
      dysfunction, has been more frequently studied in small animals with type I
      diabetes. The recent availability of transgenic models provides a new opportunity
      for further studies of diabetic uropathy in mouse models of types I and II
      diabetes mellitus.

PMID- 19846144
TI  - Diabetes and benign prostatic hyperplasia/lower urinary tract symptoms--what do
      we know?
AB  - PURPOSE: Benign prostatic hyperplasia and associated lower urinary tract symptoms
      are highly prevalent in older men and represent a substantial challenge to public
      health. Apart from the prevalence of benign prostatic hyperplasia increasing with
      age, little is understood regarding its etiology and natural history. Increasing
      evidence recently pointed toward relationships between diabetes and benign
      prostatic hyperplasia/lower urinary tract symptoms. We present an overview of the
      current understanding of clinical and epidemiological research on diabetes and
      benign prostatic hyperplasia/lower urinary tract symptoms, the hypothesized
      pathophysiological mechanisms linking the conditions and recommendations for
      future directions for research. MATERIALS AND METHODS: A structured,
      comprehensive literature review was done to identify studies of the relationships
      between benign prostatic hyperplasia and lower urinary tract symptoms, and
      diabetes in older men. RESULTS: A substantial proportion of the existing body of
      literature supports an association between diabetes and benign prostatic
      hyperplasia/lower urinary tract symptoms. However, failure to differentiate lower
      urinary tract symptoms from benign prostatic hyperplasia contributed to some of
      the confusing evidence in studies including more specific benign prostatic
      hyperplasia measurements. This could be due in part to the largely cross
      sectional analyses, the use of select or different study populations, limited
      sample sizes and inadequate control of potential confounders. CONCLUSIONS:
      Diabetes may substantially influence the risk of benign prostatic hyperplasia and
      lower urinary tract symptoms in older men. Further prospective, longitudinal
      analyses of the impact of diabetes and its etiological mechanisms on benign
      prostatic hyperplasia/lower urinary tract symptoms may identify novel
      interventions to prevent, diagnose and treat these highly prevalent conditions.

PMID- 19846145
TI  - Re: A comparative study of quality of life issues relating to open versus
      laparoscopic nephrectomy: a prospective pragmatic study. O. A. Harryman, K.
      Davenport, S. Keoghane, F. X. Keeley and A. G. Timoney. J Urol 2009; 181: 998
      1003.

PMID- 19846146
TI  - Nephrocalcinosis.

PMID- 19846147
TI  - Intrarenal artery delineation with ultra high resolution, flat panel based,
      volume computerized tomography: outer limits of spatial resolution.
AB  - PURPOSE: New methods of noninvasive high resolution imaging may improve the
      delineation of tumor microvessels and, thus, be of significant help in surgical
      planning and cost-effective monitoring of novel anti-angiogenic therapy. We
      determined the maximum delineation of intrarenal microvessels with a novel flat
      panel based volume computerized tomography system in an experimental setting.
      MATERIALS AND METHODS: We prospectively evaluated 13 porcine renal specimens for
      intrarenal vessel delineation using a prototype gantry based, flat panel, cone
      beam computerized tomography system. The gantry incorporates an array of a 40 x
      30 cm(2) CsI amorphous silicon flat panel detector consisting of a 2,048 x 1,536
      matrix. After catheterizing the renal artery with a 5Fr end hole catheter a
      contrast enhanced scan was performed using BaS as contrast medium at a dilution
      of 200 mg/ml. The diameter of all definable arterial branches was determined
      using a software tool based on Medical Imaging and Interaction Toolkit, allowing
      semi-automatic segmentation of the vessel tree. In step 1 the vessel tree is
      segmented by a 3-dimensional region growing algorithm. Following its medial axis
      the vessel tree is extracted and converted to a representation, including the
      diameter of the vessels. RESULTS: In each kidney an average +/- SD of 47,454 +/-
      22,382 arterial branches could be delineated. The diameter of the branches was
      0.029 (mean 0.032 +/- 0.0025) to 3.444 mm (mean 1.813 +/- 0.6139) with a median
      of 0.263 mm. Of visible intrarenal arteries 2.7% had a vessel diameter of 0.029
      mm. CONCLUSIONS: Flat panel based volume computerized tomography can visualize
      intrarenal microvessels down to a diameter of 0.03 mm. It may improve the
      assessment of renal microvessel architecture in healthy patients and in those
      with pathological conditions.

PMID- 19846148
TI  - Functional transient receptor potential vanilloid 1 is expressed in human
      urothelial cells.
AB  - PURPOSE: We investigated the expression and functional status of TRPV1 receptor
      in human urothelial cells. MATERIAL AND METHODS: Human urothelium was cultured
      and TRPV1 receptor expression was studied by immunocytochemistry and reverse
      transcriptase-polymerase chain reaction. The influence of inflammatory mediators
      on TRPV1 mRNA levels was also studied. Functional assays (cobalt uptake
      measurements and whole cell voltage clamp records) were used to study the
      response of urothelial cells to capsaicin, temperature, low pH and inflammatory
      mediators. Capsaicin induced adenosine triphosphate release from urothelial cells
      was assessed by bioluminescence. RESULTS: TRPV1 protein and mRNA were detected in
      human urothelial cells and mRNA more than tripled in the presence of inflammatory
      mediators. Nerve growth factor treatment alone did not affect TRPV1 mRNA
      expression. Capsaicin (100 nM and 1 microM) and heat (41C and 45C) evoked cobalt
      uptake and inflammatory mediators lowered the temperature threshold for TRPV1
      activation to 37C. Capsaicin (1 microM) induced TRPV1 desensitization to further
      applications of the agonist. In whole cell patch clamp experiments 1 microM
      capsaicin and a heat ramp from 37C to 50C caused inward currents. The same
      concentration of capsaicin induced the release of about 7 fmol adenosine
      triphosphate per mg. CONCLUSIONS: TRPV1 receptors expressed by human urothelial
      cells respond to capsaicin and thermal stimuli. Capsaicin evoked release of
      adenosine triphosphate suggests that human urothelial TRPV1 is involved in the
      afferent branch of the micturition reflex. Inflammatory mediators decrease the
      TRPV1 thermal threshold of activation to body temperature and increase its
      expression. This finding may be relevant for symptoms associated with cystitis.

PMID- 19846149
TI  - Effectiveness of doxazosin in treatment of distal ureteral stones in children.
AB  - PURPOSE: We evaluated the effectiveness of doxazosin in children with distal
      ureteral stones in terms of stone expulsion rates and time to expulsion.
      MATERIALS AND METHODS: A total of 39 patients 2 to 14 years old with lower
      ureteral stones smaller than 10 mm were enrolled and randomly divided into 2
      groups. Group 1 consisted of 20 controls receiving ibuprofen for pain and group 2
      consisted of 19 patients receiving doxazosin. Doxazosin dose was approximately
      0.03 mg/kg daily. All patients were evaluated with x-ray, ultrasound or spiral
      computerized tomography. Stone expulsion rates and time to expulsion between the
      groups were compared. Mean followup was 19 days. Effects of doxazosin were also
      evaluated by comparing subgroups with stones smaller than 5 mm and 5 to 10 mm.
      Results were also evaluated with special emphasis on gender and age. RESULTS:
      Expulsion was observed in 14 patients (70%) in group 1 and 16 (84%) in group 2 (p
      >0.05). Mean expulsion times for groups 1 and 2 were 6.1 and 5.9 days,
      respectively (p >0.05). Although fewer pain episodes were observed in the
      treatment group, this finding could not be evaluated objectively. None of the
      patients experienced any adverse effects. CONCLUSIONS: Administration of 0.03
      mg/kg doxazosin daily in children to treat distal ureteral stones up to 10 mm is
      not superior to analgesic alone. This result is not affected by gender, stone
      size or patient age. However, additional randomized controlled studies,
      especially including larger stone volumes, and different doses of doxazosin and
      other alpha-blockers, might highlight the usefulness of alpha-blockers for
      ureteral stones in children.

PMID- 19846152
TI  - Editorial comment.

PMID- 19846153
TI  - Editorial comment.

PMID- 19846154
TI  - Risk factors for nocturnal enuresis in school-age children.
AB  - PURPOSE: Although nocturnal enuresis is common in children, its etiology is
      multifactorial and not fully understood. We evaluated potential risk factors for
      presence and severity of nocturnal enuresis. MATERIALS AND METHODS: A validated,
      reproducible questionnaire was distributed to 8,230 school children in Sydney,
      Australia. Nocturnal enuresis was defined as any wetting in the previous month
      and categorized as mild (1 to 6 nights), moderate (7 or more nights but less than
      nightly) or severe (nightly). RESULTS: Parents of 2,856 children (mean +/- SD age
      7.3 +/- 1.3 years) completed the questionnaire (response rate 35%). Overall
      prevalence of nocturnal enuresis was 18.2%, with 12.3% of patients having mild,
      2.5% moderate and 3.6% severe enuresis. Multivariate analysis showed that daytime
      incontinence (OR 4.8, 95% CI 2.9 to 7.9), encopresis (OR 2.7, 95% CI 1.6 to 4.4),
      bladder dysfunction (OR 3.6, 95% CI 2.4 to 5.3) and male gender (OR 2.0, 95% CI
      1.3 to 3.1) were associated with severe nocturnal enuresis after adjustment for
      age. Emotional stressors (OR 2.3, 95% CI 1.2 to 4.2) and social concerns (OR 2.4,
      95% CI 1.2 to 4.5) were associated with moderate nocturnal enuresis only.
      CONCLUSIONS: Encopresis and daytime incontinence are significant modifiable risk
      factors for nocturnal enuresis. Expressed as population attributable risk, 23% of
      nocturnal enuresis is associated with encopresis and daytime incontinence.
      Psychosocial factors appear to contribute to moderate but not severe nocturnal
      enuresis.

PMID- 19846156
TI  - Re: Polymorphisms of the serotonin transporter gene and their relation to
      premature ejaculation in individuals from Iran. M. R. Safarinejad. J Urol 2009;
      181: 2656-2661.

PMID- 19846157
TI  - Extramammary Paget's disease of the penis and scrotum.

PMID- 19846158
TI  - Editorial comment.

PMID- 19846160
TI  - Editorial comment.

PMID- 19846161
TI  - Algorithm for comprehensive approach to hypospadias reoperation using 3
      techniques.
AB  - PURPOSE: We describe comprehensive hypospadias reoperation based on presence or
      absence of a supple urethral plate using the 3 surgical techniques of
      transurethral incised plate, 1-stage inlay graft and 2-stage buccal graft.
      MATERIALS AND METHODS: We reviewed prospective data from all reoperative
      hypospadias urethroplasties performed by one of us (WTS) between 2000 and 2008.
      Patient age, number of operations, indications for additional surgery, meatal
      location, reoperative surgical technique and outcomes were extracted. RESULTS: A
      total of 133 patients underwent reoperation by transurethral incised plate (69),
      1-stage inlay graft (16) or 2-stage buccal graft (48) urethroplasty. Mean number
      of prior failed repairs was 1.1, 1.9 and 4.3, respectively. Followup was
      available in 121 patients (91%), with 90 (74%) undergoing 1 successful
      reoperative urethroplasty. Complications occurred in 19%, 15% and 38% of
      patients, respectively, and most often consisted of fistulas or glans dehiscence.
      CONCLUSIONS: Hypospadias reoperation can be accomplished using these 3 techniques
      without skin flaps, a potential advantage given the relative paucity of skin
      after failed repair. Fistulas after transurethral incised plate urethroplasty
      correlate with barrier layers used, while glans dehiscence is more likely in 2
      stage buccal graft repairs when cheek rather than lip is used within the glans.

PMID- 19846162
TI  - Editorial comment.

PMID- 19846163
TI  - Comparison of semi-empirical and computer derived methods for estimating urinary
      saturation of calcium oxalate.
AB  - PURPOSE: Estimating calcium oxalate saturation in human urine is critical for
      nephrolithiasis clinical research and practice. The Joint Expert Speciation
      System (Mayhem Unit Trust and Council for Scientific and Industrial Research,
      Pretoria, South Africa) computer program has questioned the validity of the
      widely used EQUIL 2 program in estimating calcium oxalate urinary saturation. To
      attempt resolution the computer model based supersaturation index (by the Joint
      Expert Speciation System) and the relative saturation ratio (by EQUIL 2) were
      compared with the experimentally derived activity product ratio, that is the
      ratio of activity products before and after incubating urine with synthetic
      calcium oxalate. MATERIALS AND METHODS: To determine the experimental conditions
      required to attain calcium oxalate steady state solubility the filtrate
      concentration product of calcium and oxalate was determined after incubating 8
      urine samples with 2 to 15 mg/ml calcium oxalate for various intervals. In 20
      urine samples the activity product ratio of calcium oxalate was compared with the
      relative saturation ratio and the supersaturation index. RESULTS: Steady state
      solubility occurred after incubating 15 mg calcium oxalate per ml urine for 72
      hours. The mean +/- SD supersaturation index of 4.92 +/- 2.57 in the original
      urine samples closely approximated the activity product ratio of 5.08 +/- 3.10
      but the relative saturation ratio of 7.47 +/- 3.89 was significantly higher than
      the activity product ratio. The supersaturation index was recalculated after
      omitting soluble complexes recognized by the Joint Expert Speciation System but
      not by EQUIL 2, including Ca(2)H(2)(PO(4))(2) and (CaCitPO(4))(4-). The corrected
      supersaturation index was compared with the relative saturation ratio. After
      correction the supersaturation index increased to 7.28 +/- 3.81, which was not
      significantly different from the relative saturation ratio. CONCLUSIONS: The
      Joint Expert Speciation System is more accurate than EQUIL 2 to estimate calcium
      oxalate saturation, probably by accounting for Ca(2)H(2)(PO(4))(2),
      (CaCitPO(4))(4-), and other minor complexes of calcium and oxalate.

PMID- 19846164
TI  - Prospective study of transcutaneous parasacral electrical stimulation for
      overactive bladder in children: long-term results.
AB  - PURPOSE: We evaluated the long-term success of transcutaneous parasacral
      electrical stimulation for overactive bladder in children. MATERIALS AND METHODS:
      We prospectively evaluated children who underwent transcutaneous parasacral
      electrical stimulation for overactive bladder. All patients had symptoms of
      overactive bladder, bell curve in uroflowmetry and low post-void residual urine.
      The procedure was performed using a frequency of 10 Hz for 20-minute sessions 3
      times weekly for a maximum of 20 sessions. Initial and long-term (more than 6
      months) success rates were evaluated. RESULTS: Transcutaneous parasacral
      electrical stimulation was performed in 36 girls and 13 boys with a mean age of
      10.2 years (range 5 to 17). Mean followup was 35.3 months (range 6 to 80). Before
      treatment urgency, daytime incontinence and urinary tract infection were seen in
      100%, 88% and 71% of cases, respectively. Initial success (full response) was
      demonstrated in 79% of patients for urgency, 76% for incontinence and 77% for all
      symptoms. Continued success was seen in 84% of patients for urgency, 74% for
      daytime incontinence and 78% for all symptoms. If the 30 patients with at least 2
      years of followup were considered, treatment was successful in 73%. Recurrence of
      symptoms after a full response was seen in 10% of cases. Two of 33 patients (6%)
      with urinary tract infection before the procedure still had infection after
      treatment. CONCLUSIONS: Transcutaneous parasacral electrical stimulation is well
      tolerated, and demonstrates short and long-term effectiveness in treating
      overactive bladder in children. Symptoms eventually will recur in 10% of
      patients.

PMID- 19846165
TI  - Optimizing orthotopic bladder tumor implantation in a syngeneic mouse model.
AB  - PURPOSE: We established a reliable technique for orthotopically implanting
      bladder tumor cells in a syngeneic mouse model. MATERIALS AND METHODS: MBT-2
      murine bladder cancer cells were transurethrally implanted in the bladder of
      syngeneic C3H/He mice (Jackson Laboratory, Bar Harbor, Maine). Different chemical
      pretreatments were used before tumor implantation, including phosphate buffered
      saline (control), HCl, trypsin and poly-L-lysine. MBT-2 cells (1 x 10(6) or 2 x
      10(6)) were instilled into the intravesical space after chemical pretreatment.
      Tumor take and bladder tumor volume were determined by micro ultrasound. Bladders
      were harvested at the end of the study to measure bladder weight and for
      histopathological examination. RESULTS: Bladder pretreatment with HCl in 5
      preparations was discontinued due to significant adverse reactions, resulting in
      death in 1 mouse, and severe bladder inflammation and hematuria 3 days after
      pretreatment in 2. Pretreatment with phosphate buffered saline, trypsin and poly
      L-lysine in 6 animals each was tolerated well without significant adverse
      reactions or mortality. The tumor take rate in the control, trypsin and poly-L
      lysine pretreatment groups was 33%, 83% and 83%, respectively. The take rate was
      higher in mice instilled with 2 x 10(6) cells than in those with 1 x 10(6) cells
      (93% vs 73%, p <0.05). CONCLUSIONS: We report a reliable, feasible method of
      orthotopically implanting bladder tumor cells into a syngeneic mouse model. Poly
      L-lysine and trypsin are useful adjunctive pretreatment agents to improve bladder
      tumor uptake. This model may be suitable to evaluate treatment paradigms for
      bladder cancer.

PMID- 19846166
TI  - Temporal and spatial trends of total petroleum hydrocarbons in the seawater of
      Bohai Bay, China from 1996 to 2005.
AB  - The temporal and spatial distribution of total petroleum hydrocarbons (TPH) in
      the seawater of Tianjin Bohai Bay during 1996-2005 was investigated for the first
      time. TPH concentrations in 480 seawater samples collected from 16 stations
      during a 10-year span were quantified by ultra-violet fluorescence spectroscopy.
      Petroleum hydrocarbons were ubiquitous in the seawater, and their concentrations
      were highly variable, ranging from 23.7 to 508 microg L(-1). TPH concentrations
      in the seawater varied with seasons, showing a decreasing order of
      winter>spring>summer. Over the 10-year period, TPH at all stations steadily
      decreased. The highest values obtained were at stations near the port areas and
      Dagu outfall where shipping activities and land-based waste water discharges were
      the major sources of pollution. Our results provided the background information
      on the extent of TPH contamination in the seawater and highlighted the need to
      further control TPH pollution in Tianjin Bohai Bay.

PMID- 19846167
TI  - Protein nitration is associated with increased proteolysis in skeletal muscle of
      bile duct ligation-induced cirrhotic rats.
AB  - Cirrhosis is characterized by skeletal muscle wasting. In this study, the effects
      of nitric oxide production on skeletal muscle protein nitration and degradation
      in cirrhosis were investigated. Cirrhosis was induced by bile duct ligation (BDL)
      in Sprague-Dawley rats for 4 weeks. The BDL-induced cirrhotic rats and sham
      operated rats were then injected daily with either saline or N(G)-l-nitro
      arginine methyl ester (l-NAME) for 7 days from week 4 to week 5, after which
      nitrite/nitrate, glutathione reduction, as well as protein nitration,
      ubiquitination, and degradation were assessed in skeletal muscle. Elevated
      muscular nitrite/nitrate concentrations, protein nitration, total ubiquitin
      conjugates, and degradation fragments of myosin heavy chain as well as diminished
      glutathione reduction levels were observed in BDL-induced cirrhotic rats as
      compared with controls. Administration of l-NAME for 1 week led to reduction of
      nitrite/nitrate levels; protein nitration was also decreased in the skeletal
      muscle. In addition, ubiquitination of muscular proteins and degradation of
      myosin heavy chain were significantly diminished after treatment of l-NAME. In
      conclusion, nitrosative stress occurred in the skeletal muscle of BDL-induced
      cirrhotic rats and may lead to increased proteolysis of muscle-specific
      structural proteins.

PMID- 19846168
TI  - Serum leptin is associated with metabolic syndrome in obese and nonobese Korean
      populations.
AB  - Leptin is mainly secreted from adipose tissue and is known to be associated with
      cardiovascular diseases. However, there are not many studies on the association
      between serum leptin and metabolic syndrome. The objective of this study was to
      determine the association between serum leptin and metabolic syndrome among the
      Korean adult population. The study population consisted of 3,272 Koreans (men:
      1,915, women: 1,357) 30 to 84 years of age who had visited the Health Examination
      Center. Leptin levels were divided into quintiles and metabolic syndrome was
      defined by NCEP ATP III. The serum leptin levels increased as the number of
      components present for metabolic syndrome increased. Controlling for age,
      smoking, exercise, and LDL cholesterol, subjects with high leptin levels were
      more likely to have an elevated risk of metabolic syndrome than those with lower
      levels in both men and women. Subjects in the highest leptin quintile were found
      to have a higher risk of having metabolic syndrome than those in the lowest
      quintile (OR = 11.51 for men; OR = 4.65 for women). After further adjustment of
      the BMI, the risk of metabolic syndrome still increased slightly for men but not
      for women in increasing leptin categories. This association of leptin levels and
      metabolic syndrome did not change after stratification into obese and nonobese
      weight status. Serum leptin is associated with metabolic syndrome in Korean
      populations independent of body mass index. Thus, the reduction of circulating
      leptin may confer cardiovascular and metabolic protective effects regardless of
      weight status.

PMID- 19846169
TI  - Administration of physiologic levels of triiodothyronine increases leptin
      expression in calorie-restricted obese rats, but does not influence weight loss.
AB  - Obesity has become a major public health problem, most commonly treated via
      dietary restriction to promote weight loss. Although leptin and thyroid hormones
      are involved in the regulation of energy balance, the role of these hormones
      after the stabilization of weight loss remains unclear. This study was designed
      to analyze the effect of thyroid hormone on sustained weight loss and leptin gene
      expression in obese animals after a loss of 5% to 10% of body weight. Thirty-day
      old male Wistar rats were separated into 4 groups: control, obese, calorie
      restriction (CR), and calorie restriction with triiodothyronine administration
      (CRT). The obese group had increased weight and adiposity, leptin and insulin
      levels, and leptin gene expression. Dietary restriction in the CR group resulted
      in decreased body weight and adiposity, diminished leptin, and increased thyroid
      hormone receptor beta expression. The CRT group, submitted to dietary restriction
      with concomitant administration of a physiologic triiodothyronine dose, had
      thyroid hormone receptor beta expression at levels comparable with those observed
      in the control group and simultaneously increased leptin expression as compared
      with that in the CR group, suggesting that thyroid hormone modulates leptin
      expression under conditions of calorie restriction. Increased leptin expression
      in the CRT group did not result in increased circulating leptin or a
      statistically significant reduction in body weight during the treatment period.
      These data provide impetus for further study, as a longer treatment period may
      result in increased circulating leptin and, thus, further reduction in body
      weight during calorie restriction in an obesity model.

PMID- 19846170
TI  - Elevation of plasma retinol-binding protein 4 and reduction of plasma adiponectin
      in subjects with cerebral infarction.
AB  - The present study was undertaken to determine plasma retinol-binding protein 4
      (RBP4) and adiponectin levels in subjects with cerebral infarction. Fifty-eight
      subjects with cerebral infarction and 53 age- and sex-matched control subjects
      were enrolled. Plasma RBP4, adiponectin, and high-molecular-weight adiponectin
      were measured by the method of enzyme-linked immunosorbent assay. Plasma RBP4 was
      16.4 +/- 2.8 microg/mL in the subjects with cerebral infarction, a value
      significantly greater than that of 10.1 +/- 1.2 microg/mL in the controls (P =
      .044). Inversely, plasma adiponectin was significantly less in the subjects with
      cerebral infarction than the control subjects (8.1 +/- 0.8 vs 10.8 +/- 0.7
      microg/mL, P = .015). However, there was no difference in plasma high-molecular
      weight adiponectin between the 2 groups of subjects. In the control subjects,
      there were negative correlations between plasma RBP4 and adiponectin and between
      plasma RBP4 and high-molecular-weight adiponectin levels; and they totally
      disappeared in the subjects with cerebral infarction. The multiple regression
      analysis showed that adiponectin and hypertension were independent factors
      contributing to cerebral infarction (P < .001). These findings indicate that
      hypoadiponectinemia is concomitantly involved in the pathogenesis of
      atherosclerosis, and that an elevation of plasma RBP4 may be a useful marker for
      the development of atherosclerosis, in subjects with cerebral infarction.

PMID- 19846171
TI  - The association of tumor necrosis factor alpha receptor 2 and tumor necrosis
      factor alpha with insulin resistance and the influence of adipose tissue
      biomarkers in humans.
AB  - Tumor necrosis factor alpha (TNFalpha) is a proinflammatory adipokine
      hypothesized to link obesity with insulin resistance. Functional studies suggest
      that TNFalpha acts through pathways involving adipokines and fatty acids to
      induce insulin resistance. We tested the hypothesis that the association of
      measures of TNFalpha activity with insulin resistance is independent of obesity
      and adipose tissue biomarkers. We analyzed data from 2131 participants (without
      diabetes) of the Framingham Offspring Study examination 7. The outcome of
      interest was insulin resistance, measured using the homeostasis model assessment
      (HOMA-IR). Tumor necrosis factor alpha activity was measured by plasma tumor
      necrosis factor alpha receptor 2 (TNFr2) or TNFalpha; possible confounders
      included adipose tissue biomarkers (plasma adiponectin, resistin, and
      triglycerides). We used multivariable age- and sex-adjusted linear regression
      analyses to adjust for waist circumference and for biomarkers individually and
      simultaneously, and in biomarker-stratified (above and below median) models. We
      found that TNFr2 was positively associated with HOMA-IR (r = 0.21, P < .0001). In
      age- and sex-adjusted model, for each increase of 1 standard deviation of TNFr2
      (SD = 746 pg/mL), the log (HOMA-IR) value was increased by 0.11 units (P <
      .0001). Adjustment for waist circumference reduced the TNFr2 beta-coefficient (by
      about 45%), but the association between TNFr2 and HOMA-IR remained significant (P
      < .0001). Tumor necrosis factor alpha receptor 2 was still associated to HOMA-IR
      after adding adiponectin, resistin, and triglycerides (individually and
      simultaneously). We found similar associations with plasma levels of TNFalpha. We
      conclude that, in a representative community sample, measures of TNFalpha
      activity are associated with insulin resistance, even after accounting for
      central adiposity and other adipose tissue biomarkers.

PMID- 19846172
TI  - Variable phenotypic expression of chylomicron retention disease in a kindred
      carrying a mutation of the Sara2 gene.
AB  - Chylomicron retention disease is a recessive inherited disorder characterized by
      fat malabsorption and steatorrhea and is associated with failure to thrive in
      infancy. We describe a kindred carrying a mutation of Sara2 gene causing a
      chylomicron retention phenotype. The proband was a 5-month-old baby, born of
      consanguineous, apparently healthy parents from Morocco, with failure to thrive.
      There was a large quantity of fats in feces and malabsorption of fat-soluble
      vitamins. Intestinal biopsies showed a diffused enterocyte vacuolization with
      large cytosolic lipid droplets. Chylomicron retention disease or Anderson disease
      was hypothesized, and the Sara2 gene was analyzed by direct sequencing. Analysis
      of the Sara2 gene in the proband identified a 2-nucleotide homozygous deletion in
      exon 3 leading to a premature stop codon (c.75-76 del TG-L28fsX34). The father
      was heterozygous for the same mutation, whereas the proband's mother was
      homozygous, suggesting a variable phenotypic expression of the molecular defect.
      More studies are needed to understand the reasons of the phenotypic variability
      of the same molecular defect in the same family.

PMID- 19846173
TI  - Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a
      South Indian population.
AB  - Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone
      receptor of ligand-dependent transcription factor involved in adipogenesis and a
      molecular target of the insulin sensitizers thiazolidinediones. We addressed the
      question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the
      PPARG2 gene are associated with type 2 diabetes mellitus and its related traits
      in a South Indian population. The study subjects (1000 type 2 diabetes mellitus
      and 1000 normal-glucose-tolerant subjects) were chosen randomly from the Chennai
      Urban Rural Epidemiology Study, an ongoing population-based study in southern
      India. The variants were screened by single-stranded conformational variant,
      direct sequencing, and restriction fragment length polymorphism. Linkage
      disequilibrium was estimated from the estimates of haplotypic frequencies. The 
      1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated
      with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the
      presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter
      variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio,
      2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of
      12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes
      mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The
      3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His)
      haplotype was associated with a reduced risk of type 2 diabetes mellitus (P <
      .0001). Although our data indicate that the PPARG2 gene variants, independently,
      have no association with type 2 diabetes mellitus, the 2-loci genotype analysis
      involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have
      shown a significant association with type 2 diabetes mellitus in this South
      Indian population.

PMID- 19846174
TI  - Relationship between plasma uridine and urinary urea excretion.
AB  - To investigate whether the concentration of uridine in plasma is related to the
      urinary excretion of urea, 45 healthy male subjects with normouricemia and normal
      blood pressure were studied after providing informed consent. Immediately after
      collection of 24-hour urine, blood samples were drawn after an overnight fast
      except for water. The contents of ingested foods during the 24-hour urine
      collection period were described by the subjects and analyzed by a dietician.
      Simple regression analysis showed that plasma uridine was correlated with the
      urinary excretions of urea (R = 0.41, P < .01), uric acid (R = 0.36, P < .05),
      and uridine (R = 0.30, P < .05), as well as uric acid clearance (R = 0.35, P <
      .05) and purine intake (R = 0.30, P < .05). In contrast, multiple regression
      analysis showed a positive relationship only between plasma uridine and urinary
      excretion of urea. These results suggest that an increase in de novo pyrimidine
      synthesis leads to an increased concentration of uridine in plasma via nitrogen
      catabolism in healthy subjects with normouricemia and normal blood pressure.

PMID- 19846175
TI  - Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and
      raises serum free fatty acid levels in vivo.
AB  - Thyroid-stimulating hormone (TSH) stimulates adipocyte lipolysis, but signal
      transduction pathways activated by TSH for this response have not been directly
      studied. Using differentiated 3T3-L1 adipocytes as well as primary human
      adipocytes, we characterized the lipolytic action of TSH with dose-response and
      time-course studies, and compared it with isoproterenol. Thyroid-stimulating
      hormone stimulated phosphorylation of perilipin and hormone-sensitive lipase
      (HSL). Inhibition of protein kinase A with H89 blocked TSH-stimulated lipolysis
      as well as phosphorylation of perilipin and HSL. Thyroid-stimulating hormone
      stimulated lipolysis in vivo, as indicated by an elevation in serum free fatty
      acid (FFA) levels after recombinant human TSH administration to thyroidectomized
      patients (42% increase, n = 19, P < .05). For patients with a body mass index
      less than 30 kg/m(2), the TSH-induced increase in serum FFA levels was 53% (n =
      11, P < .05), whereas levels in patients with a body mass index of at least 30
      kg/m(2) (n = 8) did not change after TSH treatment. In summary, TSH stimulates
      lipolysis and phosphorylation of perilipin and HSL in a protein kinase A
      dependent manner in differentiated adipocytes in culture and raises serum FFA
      levels in vivo.

PMID- 19846177
TI  - Carotid intima-media thickness, dietary intake, and cardiovascular phenotypes in
      adolescents: relation to metabolic syndrome.
AB  - Little is known about the interrelationships between metabolic syndrome (MS),
      uric acid, and early carotid atherosclerosis with diet in adolescents. We
      investigated associations among diet, carotid intima-media thickness (cIMT), MS,
      uric acid, and other cardiovascular risk factors in adolescents. Two hundred
      forty-nine adolescents from 3 high schools in Central California-a predominately
      Hispanic (n = 119, 16.1 +/- 0.9 years old, 94% Hispanic), a mixed-ethnicity (n =
      94, 15.7 +/- 1.2 years old), and a Seventh-day Adventist (SDA) (n = 33, 17.0 +/-
      1.3 years old) high school-were assessed for cIMT, blood lipids, uric acid, blood
      glucose, systolic and diastolic blood pressure, body mass index (BMI), and
      dietary intake. Compared with SDA adolescents, the predominately Hispanic and
      mixed-ethnicity high school adolescents exhibited higher low-density lipoprotein
      and BMI percentile, whereas adolescents from the SDA and mixed-ethnicity high
      schools exhibited lower uric acid and fasting glucose levels than those from the
      Hispanic high school. After adjusting for age and sex, cIMT was only correlated
      with systolic blood pressure percentile (r = 0.16, P < .01). Controlling for age,
      levels of uric acid were correlated with BMI percentile (males: r = 0.59, P <
      .001; females: r = 0.24, P < .01), low-density lipoprotein (males: r = 0.40, P <
      .001; females: r = 0.20, P < .01), and total cholesterol in males (r = 0.38, P <
      .001). Despite no significant differences in the high school frequency of MS risk
      factors, 59% of adolescents had one or more MS risk factors. A relationship was
      noted between the number of MS risk factors and uric acid (P < .002). Most of the
      adolescents presented MS risk factors independent of ethnicity or a purportedly
      healthier lifestyle (SDA). Uric acid association with MS and its risk factors
      suggests its potentially heightened importance for the assessment of adolescent
      cardiovascular health.

PMID- 19846176
TI  - PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in
      Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor.
AB  - We have examined the association of 14 tagging single nucleotide polymorphisms
      (tagSNPs) in peroxisome proliferator activated receptor-gamma transcripts 1 and 2
      (PPARG1 and 2) and 5 tagSNPs in adiponectin (ADIPOQ) genes for their effect on
      type 2 diabetes mellitus (T2D) risk in Asian Indian Sikhs. A total of 554 T2D
      cases and 527 normoglycemic controls were examined for association with T2D and
      other subphenotypes of T2D. With the exception of a strong association of
      PPARG2/Pro12Ala with T2D (odds ratio, 0.13; 95% confidence interval, 0.03-0.56; P
      = .0007), no other tagSNP in the PPARG locus revealed any significant association
      with T2D in this population. Similarly, none of the tagSNPs in the ADIPOQ gene
      was associated with T2D susceptibility in single-site analysis. However,
      haplotype analysis provided strong evidence of association of these loci with
      T2D. Three-site haplotype analysis in the PPARG locus using the 2 marginally
      associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala
      (P/rs1801282) revealed a strong association of 1 "risk" (CGC) (P = .003,
      permutation P = .015) and 1 "protective" (CAC) (P = .001, permutation P = .005)
      haplotype associated with T2D. However, the major effect still appears to be
      driven by Pro12Ala, as the association of these haplotypes did not remain
      significant when analyzed conditional upon Pro12Ala (P = .262). In addition, 2
      site haplotype analysis in the ADIPOQ locus using only 2 marginally associated
      SNPs (AD/rs182052 and AD/rs7649121) revealed a significant protective association
      of the GA haplotype with T2D (P = .009, permutation P = .026). Multiple linear
      regression analysis also revealed significant association of an ADIPOQ variant
      (AD/rs12495941) with total body weight (P = .010), waist (P = .024), and hip (P =
      .021), although these associations were not significant after adjusting for
      multiple testing. Our new findings strongly suggest that the genetic variation in
      PPARG and ADIPOQ loci could contribute to the risk for the development of T2D in
      Indian Sikhs. Identification of causal SNPs in these important biological and
      positional candidate genes would help determine the true physiologic significance
      of these loci in T2D and obesity.

PMID- 19846178
TI  - Insulin sensitivity, metabolic flexibility, and serum adiponectin concentration
      in women with anorexia nervosa.
AB  - Anorexia nervosa (AN) is an eating disorder resulting in sustained low weight and
      marked decrease in fat mass. The lack of adipose tissue observed in
      lipodystrophies is accompanied by insulin resistance. It remains unclear if the
      same phenomenon would be present in AN. The objective of the study was to
      estimate insulin sensitivity, oxidative and nonoxidative glucose metabolism in
      insulin-stimulated conditions, metabolic flexibility, and serum adiponectin
      concentration in women with AN. We examined 21 women with AN and 24 healthy
      normal-weight female controls. Euglycemic hyperinsulinemic clamp, indirect
      calorimetry, and the measurement of serum adiponectin concentration were
      performed in all the subjects. We did not observe differences in insulin
      sensitivity, oxidative and nonoxidative glucose metabolism in insulin-stimulated
      conditions, and metabolic flexibility between AN and control subjects. Serum
      adiponectin was higher in AN women in comparison with control group (P = .002).
      Women with AN have normal insulin sensitivity because of the preserved response
      of glucose oxidation, nonoxidative glucose metabolism in response to insulin, and
      normal metabolic flexibility. High adiponectin concentration and normal insulin
      sensitivity in anorectic women suggest that in AN the adipocytes are still
      capable of functioning at the level that is sufficient to prevent the metabolic
      consequences.

PMID- 19846179
TI  - Interindividual variations in resting metabolic rate during weight loss in obese
      postmenopausal women A pilot study.
AB  - The objective of the study was to examine if decreases in resting metabolic rate
      (RMR) take place early in the weight loss process and if they remain throughout
      the duration of the weight loss intervention. Twenty obese postmenopausal women
      (61.8 +/- 5.9 years) participated in a 15-week weight loss program. After the
      fifth week, subjects were characterized as having an increased (>5%) or a
      decreased (<5%) RMR based on baseline values. Afterward, they were followed for
      an additional 10 weeks. Outcome measures were as follows: fat mass ([FM] total,
      trunk), lean body mass (total, trunk), RMR, resting heart rate (RHR), and
      physical activity level. After 5 weeks, significant decreases were observed for
      lean body mass, FM, and RHR (P < .05), whereas no overall changes in physical
      activity level and RMR were observed. However, on an individual basis, large
      variations in RMR were observed (ranging from -320 to +330 kcal/d). Analyses
      showed that subjects characterized as either having an increased or a decreased
      RMR after the fifth week maintained these adaptations at the end of intervention.
      Finally, subjects displaying a decreased RMR during weight loss had a
      significantly higher RMR and lower FM accumulations at baseline (total and trunk)
      compared with those with an increased RMR. Interindividual variations in RMR took
      place early in the weight loss process and were maintained over the duration of
      the weight loss program in our cohort of obese postmenopausal women. Baseline
      RMR, changes in RHR, and FM accumulations (total and trunk) seem to be important
      factors to consider when studying the effects of weight loss on RMR.

PMID- 19846180
TI  - Inhibitory effects of ursolic acid on hepatic polyol pathway and glucose
      production in streptozotocin-induced diabetic mice.
AB  - The effects of ursolic acid on the polyol pathway and glucose homeostasis-related
      metabolism were examined in the livers of streptozotocin (STZ)-induced diabetic
      mice fed a high-fat (37% calories from fat) diet for 4 weeks. Male mice were
      divided into nondiabetic, diabetic control, and diabetic-ursolic acid (0.05%
      wt/wt) groups. Diabetes was induced by the injection of STZ (200 mg/kg body
      weight, intraperitoneally). Although an ursolic acid supplement lowered the blood
      glucose level, it did not affect the plasma leptin and adiponectin levels. The
      present study shows that the blood glucose levels have a positive correlation
      with the hepatic sorbitol dehydrogenase activities (r = 0.39, P < .05). Ursolic
      acid significantly inhibited sorbitol dehydrogenase activity as well as aldose
      reductase activity in the liver. The supplementation of ursolic acid
      significantly increased glucokinase activity, while decreasing glucose-6
      phosphatase activity in the livers of STZ-induced diabetic mice. Ursolic acid
      significantly elevated the hepatic glycogen content compared with the diabetic
      control group. Supplementation with ursolic acid significantly lowered the plasma
      total cholesterol, free fatty acid, and triglyceride concentrations compared with
      the diabetic control group, whereas it normalized hepatic triglyceride
      concentration. A negative correlation was found between the hepatic triglyceride
      concentration and blood glucose levels (r = -0.50, P < .01) in regard to insulin
      dependent diabetic mice. The hepatic fatty acid synthase activity was
      significantly lower in the ursolic acid group than in the diabetic control group,
      whereas hepatic fatty acid beta-oxidation and carnitine palmitoyltransferase
      activities were significantly higher. These results indicate that ursolic acid
      may be beneficial in preventing diabetic complications by improving the polyol
      pathway as well as the lipid metabolism and that it can function as a potential
      modulator of hepatic glucose production, which is partly mediated by up
      regulating glucose utilization and glycogen storage and down-regulating
      glyconeogenesis in the liver.

PMID- 19846181
TI  - Effects of meal size and composition on incretin, alpha-cell, and beta-cell
      responses.
AB  - The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) regulate postprandial insulin release from the
      beta-cells. We investigated the effects of 3 standardized meals with different
      caloric and nutritional content in terms of postprandial glucose, insulin,
      glucagon, and incretin responses. In a randomized crossover study, 18 subjects
      with type 2 diabetes mellitus and 6 healthy volunteers underwent three 4-hour
      meal tolerance tests (small carbohydrate [CH]-rich meal, large CH-rich meal, and
      fat-rich meal). Non-model-based and model-based estimates of beta-cell function
      and incremental areas under the curve of glucose, insulin, C-peptide, glucagon,
      GLP-1, and GIP were calculated. Mixed models and Friedman tests were used to test
      for differences in meal responses. The large CH-rich meal and fat-rich meal
      resulted in a slightly larger insulin response as compared with the small CH-rich
      meal and led to a slightly shorter period of hyperglycemia, but only in healthy
      subjects. Model-based insulin secretion estimates did not show pronounced
      differences between meals. Both in healthy individuals and in those with
      diabetes, more CH resulted in higher GLP-1 release. In contrast with the other
      meals, GIP release was still rising 2 hours after the fat-rich meal. The initial
      glucagon response was stimulated by the large CH-rich meal, whereas the fat-rich
      meal induced a late glucagon response. Fat preferentially stimulates GIP
      secretion, whereas CH stimulates GLP-1 secretion. Differences in meal size and
      composition led to differences in insulin and incretin responses but not to
      differences in postprandial glucose levels of the well-controlled patients with
      diabetes.

PMID- 19846182
TI  - Obesity and diabetic hyperglycemia were associated with serum alanine
      aminotransferase activity in patients with hepatitis B infection.
AB  - Several studies have reported that obesity and diabetes are important risk
      factors for elevated blood aminotransferase activity in individuals with no
      underlying causes of liver disease. The aim of this study was to determine
      whether obesity and fasting glucose level were associated with hepatic
      dysfunction in patients with hepatitis B infection. A total of 934 patients with
      hepatitis B infection were enrolled, among whom increased alanine
      aminotransferase (ALT) activity (> or =40 IU/L) was observed in 25.1%. By
      univariate analysis, factors associated with increased ALT activity among
      patients with hepatitis B infection included body mass index (BMI), fasting blood
      glucose level, and blood triglyceride and high-density cholesterol levels. By
      multivariate logistic regression analysis, BMI and fasting blood glucose level
      were independent predictors of elevated ALT activity, with odds ratios of 1.73
      (95% confidence interval, 1.17-2.56) for subjects with a BMI greater than or
      equal to 25 kg/m2 and 1.88 (95% confidence interval, 1.06-3.33) for subjects with
      a fasting blood glucose greater than or equal to 126 mg/dL. Even in subjects with
      ALT activity within the reference range, ALT activity was found to be associated
      with BMI. In conclusion, a BMI greater than or equal to 25 kg/m2 and a fasting
      blood glucose level greater than or equal to 126 mg/dL were risk factors for
      increased ALT activity in subjects with hepatitis B infection, suggesting that
      obesity and diabetic fasting hyperglycemia may aggravate liver injury in this
      population.

PMID- 19846183
TI  - Ingestion of native and thermally oxidized polyunsaturated fats acutely increases
      circulating numbers of endothelial microparticles.
AB  - Circulating numbers of endothelial microparticles (EMP) are an index of
      endothelial injury and dysfunction; and microparticles positive to CD31 antibody
      increase acutely after cooked, fatty fast-food meals that are rich in saturated
      fatty acids (SAFA) and lipid oxidation products. The aim of this study was to
      determine the acute effect of meals rich in SAFA and native and thermally
      oxidized polyunsaturated vegetable oil on circulating numbers of EMP positive to
      CD144 antibody, a more specific marker of EMP. Twenty-two apparently healthy
      subjects received isocaloric meals rich in cream (CR), unheated sunflower oil, or
      heated sunflower oil in a randomized crossover study design. Circulating numbers
      of CD144-EMP and plasma lipids and Svedberg unit of flotation (S(f)) greater than
      400 triglyceride content were measured before and 1 and 3 hours after the meals.
      Triglycerides in the plasma S(f) greater than 400 fraction increased
      significantly (P < .001) after the meals, with a significantly (P < .05) larger
      increase after the CR meal. Plasma CD144-EMP increased significantly (20%, P <
      .05) after the unheated sunflower oil and heated sunflower oil meals and did not
      increase significantly (P = .55) after the CR meal. This response was
      significantly different among the meals (P = .002) when first-visit fasting
      plasma glucose was a covariate. In conclusion, these data suggest that ingestion
      of meals rich in n-6 polyunsaturated vegetable oil irrespective of whether it has
      been mildly thermally oxidized may acutely alter the state of the vascular
      endothelium, resulting in increased shedding of CD144-EMP. The physiologic
      implications of these findings remain to be determined.

PMID- 19846184
TI  - [Intermaxillary fixation: technique and benefit for piezosurgical sagittal split
      osteotomy].
AB  - INTRODUCTION: The aim of this study was to assess piezosurgical sagittal split
      osteotomy with peroperative inter maxillary fixation. MATERIAL AND METHOD: We
      studied 25 bimaxillary osteotomies, 50 sagittal split osteotomies performed with
      this technique. It included both maxillomandibular fixation during all the split
      osteotomy and performing split osteotomy in five steps. For each case, we noted
      the type of dysmorphia, the size of split osteotomy and the time required for
      surgery, along with common data such as sex, age, etc. The data was compared to
      results of a previous series of patients also operated with Piezosurgery but
      without peroperative maxillomandibular fixation. RESULTS: Using peroperative
      maxillomandibular fixation during piezosurgical bilateral sagittal osteotomy
      decreases the length of surgery by 33%, allows 9 times out of 10 for complete
      splitting, including the basilar edge, has no adverse effect especially on
      orthodontic material. DISCUSSION: Piezosurgery is a great progress for
      orthognatic surgery because of its precision and ability to preserve soft
      tissues. But it requires modification of the usual technique for mechanical
      section. Using peroperative inter maxillary fixation during ultrasonic splitting
      is a remarkably effective and easy technical modification.

PMID- 19846185
TI  - [Natalizumab (Tysabri) prescription practices of neurologists in southern
      France].
AB  - INTRODUCTION: Tysabri is indicated as single-drug disease-modifying therapy in
      patients with highly active relapsing remitting multiple sclerosis (RRMS).
      Potential risk for opportunistic infection and especially for progressive
      multifocal leucoencephalopathy has implied specific guidelines for use. The
      purpose of this study was to ascertain the prescription practices of neurologists
      in southern France and to learn more about how the drug is used in clinical
      practice compared with management guidelines stated in the product's
      characteristics and national recommendations. METHODS: We developed a
      questionnaire which was sent to all neurologists practicing in our region,
      whether they had multiple sclerosis patients or not. Questions regarded
      demographic data (geography, practice in hospital or private office), current
      knowledge on natalizumab (mechanism of action, indications), monitoring of
      treated patients (pre-therapeutic and therapeutic check-up), rescue decisions and
      overall experience with using natalizumab. RESULTS: Two hundred fifty
      neurologists, practicing in eight administrative districts in our region, were
      contacted. Demographic data showed that most of them were prescribing Tysabri.
      Patients treated with Tysabri were mostly followed in teaching hospitals (79%).
      Concerning knowledge about natalizumab, neurologists applied the recommended
      check-up (73%) but most of them preferred prescribing Tysabri as a second line of
      treatment after IFN failure (66%). Inefficacy was mainly evaluated on clinical
      parameters (one or two relapses under treatment with sequels or EDSS progression
      in each answer); MRI was only useful to confirm clinical conclusions, but for the
      neurologists, gadolinium enhancement was required to confirm lack of efficacy.
      DISCUSSION: Results tended to show that, in clinical practice, despite some
      deviation from national guidelines, the recommended precautions are applied for
      the use of Tysabri. Neurologists considered that Tysabri is other
      immunosuppressant drugs used in RRMS. Further medical information might be useful
      to improve compliance with all of the recommended indications and standard
      practices for patient follow-up. CONCLUSION: This survey enabled an assessment of
      current knowledge about Tysabri as a treatment for RRMS patients and to learn
      more about how it was used in real life practice during its first year of
      marketing in France.

PMID- 19846186
TI  - [Rupture of intracranial dermoid cyst with disseminated lipid droplets].
AB  - INTRODUCTION: Dermoid cysts are rare slow-growing benign tumors of the central
      nervous system generally diagnosed in the third to fifth decade. They are formed
      from inclusion of ectodermal elements during neural tube closure, and are mostly
      located along the cranial or spinal midline axis. They cause many non specific
      symptoms such as headache and seizures, and may spontaneously rupture spreading
      fatty droplets into the ventricles and subarachnoid spaces. Rupture of dermoid
      cysts causes sequelae which may vary from no symptoms to death. In general,
      subtotal surgical removal is required for ruptured dermoid cysts. CASE REPORTS:
      We report two cases of ruptured intracranial dermoid tumor with non-specific
      clinical presentations. The first rupture was asymptomatic and discovered on
      brain magnetic resonance imaging (MRI) performed for other purposes. The second
      case was identified on brain imaging performed because of daily headache. These
      dermoid cysts were not surgically treated. Surveillance was advised because of
      the spontaneously favourable outcome observed in both cases. CONCLUSION: Surgical
      removal is not the only treatment of ruptured dermoid cyst. Monitoring with brain
      MRI can be sufficient if the rupture has no severe clinical impact.

PMID- 19846187
TI  - [Botulinum neurotoxin].
AB  - Botulinum toxin is a multi-molecular complex comprised of a neuro-active moiety
      (i.e. botulinum neurotoxin) and several associated non-toxic proteins. The toxin
      dissociates rapidly at plasmatic pH, thereby releasing neurotoxin. Nerve
      terminals only take up the neurotoxin. In the peripheral nerve system, the
      neurotoxin mainly blocks acetylcholine release. When acting at the neuromuscular
      junctions, this results in paralysis of the muscle fibers. The duration of the
      neurotoxin action is mainly determined by the life-time of neurotoxin molecules
      inside the nerve terminals. Inhibition of cholinergic transmission induces rapid
      atrophy of the muscle fibres, and, sometimes, sprouting from poisoned nerve
      terminals. These effects, as well as the acetylcholine release blockade are
      entirely reversible. When injected in the periphery, a direct action of botulinum
      neurotoxin in the central nervous system remains unlikely despite its retrograde
      ascent demonstrated in animal models. However, indirect effects are numerous. The
      constituting proteins of the toxin complex can lead to immunisation against the
      non-toxic associated proteins and neurotoxin. Only the antibodies directed
      against neurotoxin are potentially neutralizing.

PMID- 19846188
TI  - Quantifying the relationship between HIV-1 susceptibility to CCR5 antagonists and
      virus affinity for antagonist-occupied co-receptor.
AB  - Previous studies have demonstrated that HIV-1 develops resistance to CCR5
      antagonists by gaining the ability to use drug-occupied co-receptor. However, the
      effects of CCR5 antagonists on the affinity of virus-co-receptor interactions
      have been difficult to quantify. We developed a pharmacological model for
      allosteric interaction at G-protein coupled receptors to analyze the effect of
      different CCR5 antagonists on infection by three laboratory adapted viruses with
      low, moderate and high susceptibility to the inhibitors. Infection data for these
      viruses fitted a model in which susceptibility to inhibition by CCR5 antagonists
      was directly related to fold reduction in virus affinity for CCR5. Dissociation
      constants for CCR5 antagonists calculated from the modeled data were consistent
      with values obtained by standard methods, suggesting that this approach can
      quantify pharmacologically relevant changes in co-receptor:ligand affinity in the
      context of infection of whole cells by authentic HIV-1 particles.

PMID- 19846189
TI  - A human coronavirus OC43 variant harboring persistence-associated mutations in
      the S glycoprotein differentially induces the unfolded protein response in human
      neurons as compared to wild-type virus.
AB  - We have reported that human respiratory coronavirus OC43 (HCoV-OC43) is
      neurotropic and neuroinvasive in humans and mice, and that neurons are the
      primary target of infection in mice, leading to neurodegenerative disabilities.
      We now report that an HCoV-OC43 mutant harboring two persistence-associated S
      glycoprotein point mutations (H183R and Y241H), induced a stronger unfolded
      protein response (UPR) and translation attenuation in infected human neurons.
      There was a major contribution of the IRE1/XBP1 pathway, followed by caspase-3
      activation and nuclear fragmentation, with no significant role of the ATF6 and
      eIF2-alpha/ATF4 pathways. Our results show the importance of discrete molecular
      viral S determinants in virus-neuronal cell interactions that lead to increased
      production of viral proteins and infectious particles, enhanced UPR activation,
      and increased cytotoxicity and cell death. As this mutant virus is more
      neurovirulent in mice, our results also suggest that two mutations in the S
      glycoprotein could eventually modulate viral neuropathogenesis.

PMID- 19846190
TI  - Fate of LCFA in the co-digestion of cow manure, food waste and discontinuous
      addition of oil.
AB  - Different concentrations of oily waste were added in a discontinuous mode and
      recurrently to anaerobic continuous stirred tank reactors fed with cow manure and
      food waste. Four continuous stirred tank reactors were run in parallel. A control
      reactor (R1) received no additional oil and R2, R3 and R4 received increasing
      concentrations of oil in two different experimental approaches. First, the lipids
      composition was forced to change suddenly, in three moments, without changing the
      total chemical oxygen demand (COD) fed to the reactors. The only long chain fatty
      acid (LCFA) detected onto the R1 solid matrix was palmitic acid (C16:0).
      Nevertheless in the solid matrix of R2, R3 and R4C16:0 and stearic acid were
      detected. For occasional increase in the oil concentration up to
      7.7gCOD(oil)/L(reactor) (55% Oil(COD)/Total(COD)) no statistical differences were
      detected between the reactors, in terms of methane production, effluent soluble
      COD, effluent volatile fatty acids and total and volatile solids removal.
      Therefore this experiment allowed to conclude that cow manure-food waste co
      digestion presents sufficient buffer capacity to endure solid-associated LCFA
      concentration up to 20-25gCOD-LCFA/kgTS. In a second experiment higher
      concentrations of oil were added, raising occasionally the concentration in the
      reactors to 9, 12, 15 and 18gCOD(oil)/L(reactor). All pulses had a positive
      effect in methane production, with the exception of the highest oil pulse
      concentration, that persistently impaired the reactor performance. This
      experiment demonstrates that threshold values for LCFA and C16:0 accumulation
      onto the solid matrix, of about 180-220gCOD-LCFA/kgTS and 120-150gCOD-C16:0/kgTS,
      should not be surpassed in order to prevent persistent reactor failure, as occurs
      in some full scale co-digestion plants.

PMID- 19846191
TI  - Synthesis, characterization, electrochemical studies and antitumor activity of
      some new chalcone analogues containing ferrocenyl pyrazole moiety.
AB  - A series of new alpha,beta-unsaturated conjugated ketones containing ferrocenyl
      pyrazole unit were synthesized and fully characterized by IR and NMR
      spectroscopy. Electrochemical characterization of subject compounds was performed
      by means of cyclic voltametry. The in vitro cytotoxic activity of all the
      synthesized compounds was studied against cervix adenocarcinoma HeLa, melanoma
      Fem-x and myelogenous leukemia K562 cell lines by the MTT method. Derivative 1l
      containing 3-pyridyl moiety exhibited a better cytotoxic activity in the cell
      growth inhibition of K562 cell lines in comparison with cisplatin as a reference
      compound.

PMID- 19846192
TI  - Biodegradation of fomesafen by strain Lysinibacillus sp. ZB-1 isolated from soil.
AB  - The fomesafen degrading bacterium ZB-1 was isolated from contaminated
      agricultural soil, and identified as Lysinibacillus sp. based on the comparative
      analysis of 16S rRNA gene. The strain could utilize fomesafen as the sole carbon
      source for growth, and the total degradation rate was 81.32% after 7 d of
      inoculation in mineral salts medium. Strain ZB-1 could also degrade other
      diphenyl ethers including lactofen and fluoroglycofen. The optimum temperature
      for fomesafen degradation by strain ZB-1 was 30 degrees C. The effect of
      fomesafen concentration on degradation was also examined. Cell-free extract of
      strain ZB-1 was able to degrade fomesafen and other diphenyl ethers. Metabolism
      of fomesafen was accompanied by a transient accumulation of a metabolite
      identified as [N-[4-{4-(trifluoromethyl)phenoxy}-2-methanamidephenyl]acetamide]
      using liquid chromatography-mass spectrometry, thus indicating a metabolic
      pathway involving reduction, acetylation of nitro groups and dechlorination. The
      inoculation of strain ZB-1 to soil treated with fomesafen resulted in a higher
      degradation rate than in noninoculated soil regardless of the soil sterilized or
      nonsterilized.

PMID- 19846193
TI  - Biomass fermentation to augment biological phosphorus removal.
AB  - A combination of a lab scale biological phosphorus removal sequencing batch
      reactor (called mother reactor) and a side-stream biomass fermenter was setup. It
      was found that when fermented biomass was recirculated back into the mother
      reactor as volatile fatty acid (VFA) supplement, the phosphate concentration in
      the effluent decreased from 6 in the control reactor to 4.5 mgL(-1) in the
      effluent from mother reactor. The addition of the fermentation effluent into the
      mother reactor increased the phosphate and ammonium loads and resulted in
      deterioration of nitrification. Phosphorus removal and nitrification improved
      when the fermented biomass was separated from the liquid phase using an up-flow
      system, followed by the addition of MgO to the supernatant to precipitate
      phosphate and ammonium. Phosphorus removal was further improved by delaying the
      time of VFA addition into mother reactor during the anaerobic period as soon as
      denitrification ceased. Biomass fermentation was found to generate 157 mg VFA-COD
      by fermenting 1g of biomass at a solids retention time of 5d. Acetate (78% of
      generated COD) and propionic acid (10%) were the major components of the produced
      VFA. It was concluded that biomass fermentation to augment a biological nutrient
      removal process can be effective if generated phosphate and ammonia are removed,
      e.g. through struvite precipitation.

PMID- 19846194
TI  - Screening of hydrophobic DNA adducts in flounder (Platichthys flesus) from the
      Baltic Sea.
AB  - Neoplasia and other histopathological lesions in flounder (Platichthys flesus)
      liver have been investigated in several European sea areas, including the Baltic
      Sea. Several studies have been able to link neoplasm epizootics in fish with the
      exposure to genotoxins such as polycyclic aromatic hydrocarbons (PAHs). The level
      of hydrophobic DNA adducts in tissue DNA reflects the exposure of the organism to
      PAHs. Using hydrophobic DNA adduct levels as biomarkers, possible PAH exposure
      was assessed in flounder from 10 different sites in the Baltic Sea, collected
      during the years 1995-1997. The results show that the overall levels of hepatic
      DNA adducts were low and, in general, the chromatograms appeared clean. The
      highest levels of DNA adducts were found at two sites in the southern Baltic Sea.
      There were no statistically significant differences in adduct levels between the
      sites. Our results indicate that flounder from studied off shore sites of the
      Baltic Sea had not been exposed to a greater extent to large polycyclic
      hydrophobic hydrocarbons in their environment.

PMID- 19846195
TI  - The inclusion of atmospheric particles into the bark suber of ash trees.
AB  - A slow deposition of atmospheric components occurs on tree barks. One part of
      them can be incorporated into bark tissues. This work demonstrates that mineral
      particles are present inside the suber tissue in four-year-old ash tree stems.
      Most of these particles are smaller than 2 microm. Scanning electronic microscope
      studies - using energy dispersive X-ray spectroscopy (SEM-EDX) - on stem cuttings
      show that they are located either inside the dead suber cells or between these
      cells. Numerous particles are composed of clay, quartz, feldspar or mica. Others,
      clearly of anthropogenic origin, are metallic fragments composed of Fe, Ni, Cr,
      Pb, etc. Spherical fly ashes were found, composed of Si, Al or Fe, and
      demonstrating an anthropogenic formation. Such particles were isolated and
      purified from suber ashes obtained at 550 degrees C, after aqueous and acidic
      treatments, and their composition was established through SEM-EDX. These results
      reinforce the idea that the suber of tree barks alone can be considered as
      archives for atmospheric deposition.

PMID- 19846196
TI  - Outdoor weathering and dissolution of TNT and Tritonal.
AB  - Low-order detonations of military munitions scatter cm-sized chunks of high
      explosives onto military range soils, where rainfall can dissolve and then
      transport the explosives to groundwater. We present 1 year of mass-loss data
      obtained from cm-sized chunks of the frequently used explosives TNT (2,4,6
      trinitrotoluene) and Tritonal (an 80:20 mixture of TNT and aluminum flakes)
      exposed outdoors to weather and dissolve under natural conditions. The explosive
      chunks rested on glass frits in individual funnels and all precipitation
      interacting with them was collected and analyzed. Mass balance data reveal that
      TNT in the water samples accounts for only about one-third of the TNT lost from
      the chunks. The creation of photo-transformation products on the solid chunks,
      and their subsequent dissolution or sublimation, probably accounts for the other
      two-thirds. Although these products cannot, as yet, be quantified they are
      intrinsic to the outdoor weathering and fate of TNT-based explosives. TNT in our
      water samples was not photo-transformed. Thus, we used the yearlong, dissolved
      mass time-series to validate a drop-impingement dissolution model for TNT. The
      model used measured rainfall and air temperature data as input, and the results
      agreed remarkably well with TNT dissolved-mass time-series measured for the year.
      This model can estimate annual TNT influx into range soils using annual rainfall
      and particle-size distributions. Nevertheless, large uncertainties remain in the
      numbers and sizes of TNT particles scattered on military ranges and the
      identities and fates of the photo-transformation products.

PMID- 19846197
TI  - Anaerobic biodegradation of organochlorine pesticides in contaminated soil -
      significance of temperature and availability.
AB  - Anaerobic biodegradation of the pesticides: gamma-hexachlorocyclohexane,
      methoxychlor, o,p'- and p,p'-DDT in field polluted soil was tested at 12, 22 and
      30 degrees C, using methanogenic granular sludge as inoculum. The contaminants
      were removed quite effectively at all temperatures and their removal rates
      increased 1.2-1.7 times with the increase in temperature. In most cases pesticide
      concentrations after an initial substantial decline remained almost constant
      until the end of experiment. These residual concentrations were also temperature
      dependent and they were 1.4-8.2 times higher at 12 degrees C than at 30 degrees
      C. DDT was degraded via DDD and accumulation of this metabolite was lower (19
      64%) than the corresponding amount of removed DDT, especially at higher
      temperatures. Further transformation of DDD was confirmed by formation of p,p'
      dichlorobenzophenone. Additional experiment demonstrated that removal was limited
      to readily desorbing fractions of pesticides, while their desorption-resistant
      fractions persisted in the soil. However, DDD metabolite was only partially
      removed despite its good desorbability.

PMID- 19846198
TI  - Environmental fate of the anthelmintic ivermectin in an aerobic sediment/water
      system.
AB  - This study investigated the long-term fate of (3)H-ivermectin and its metabolites
      in aerobic sediment/water systems. Total radioactivity in sediment and water was
      measured by Liquid Scintillation Counting and Radio-HPLC was used for
      determination of transformation products. The test system, containing a cooling
      and a water trap, showed excellent applicability for studying environmental fate
      of (3)H-labelled compounds. A complete mass balance was obtained over the whole
      duration with total recoveries ranging from 91.3% to 98.8%. In water, a DT(50)
      value of ivermectin of <6h and a DT(90)-value of 16.8 d were obtained. The DT(50)
      value of ivermectin in the entire system was 127 d. Maximum distribution
      coefficients were calculated to K(d)=160 L kg(-1) and K(oc)=3550 L kg(-1). The
      fraction of bound residues increased to a maximum percentage of 30.4% after 188
      d. In total about 31.3% of the initially applied ivermectin were transformed
      after 188 d. Two transformation products ivermectin monosaccharide and ivermectin
      aglycone, could be identified in samples from day 100 and 188, respectively.
      However, additional peaks which were observed in the radio-chromatograms indicate
      that several other transformation product are formed.

PMID- 19846199
TI  - Estimation of phosphorus content and dynamics during composting: use of near
      infrared spectroscopy.
AB  - The content and chemical forms of P in compost are essential variables for its
      proper management with an agricultural purpose, especially considering the
      increasing P over-fertilization in agrosystems. In this study, the estimation of
      P content and dynamics in different composting scenarios was developed using near
      infrared reflectance spectroscopy (NIRS) coupled with a statistical tool for
      calibration, a penalized signal regression. Samples were analyzed on total P and
      partitioned using NaOH-solution (31)P NMR spectroscopy quantifying pyrophosphate,
      orthophosphate, orthophosphate diesters, phospholipids, and orthophosphate
      monoesters pools. According to the results obtained, total P content (r(2)=0.99
      and root mean square error of cross-validation=0.53) and P forms can be estimated
      during composting using NIRS, as well as in the mature product, orthophosphate
      and orthophosphate monoesters being the most abundant P forms throughout the
      experiment. Penalized signal regression allows detecting the significant
      wavenumbers in each composting period, and also with the different P pools in the
      composting pile depending on time.

PMID- 19846200
TI  - A study on biochemical changes in the penaeid shrimp, Metapenaeus monoceros
      (Fabricius) following exposure to sublethal doses of organochlorine pesticide
      (endosulfan).
AB  - Endosulfan, a broad-spectrum non-systemic organochlorine (OC) pesticide is
      extensively used to control a wide variety of pests in agriculture, horticulture
      and public health programmes. Biochemical changes occurring in the metabolically
      active tissues of gills (GL), hepatopancreas (HP) and muscle (MU) of the penaeid
      shrimp, Metapenaeus monoceros (Fabricius) on exposure to two sublethal doses (40
      and 60 ng L(-1)) of endosulfan were studied for 23 days of exposure (DoE).
      Sublethal doses of endosulfan significantly (P<0.05) altered the levels of the
      total protein (TP), the total carbohydrates (TC), the glycogen (GLY), the total
      free sugars (TFS) and the total lipids (TL) in test shrimps. Concentrations of
      biochemical components significantly varied with the DoE but were dose
      independent (P<0.05). Percent decrease in all biochemical components increased
      with the progress of the DoE irrespective of the exposure concentrations. The
      order of percent decrease in the concentrations of the TP, TC, GLY, TL and TFS in
      different tissues at the end of 23 DoE was found to be MU>GL>HP, HP>GL>MU,
      MU>HP>GL, HP>MU>GL and MU>GL>HP, respectively. The results of the study revealed
      that sublethal doses of endosulfan significantly alters the proximate composition
      of major tissues, particularly the TP levels in the MU tissues thereby reducing
      the nutritive value of this economically important penaeid shrimp. Since M.
      monoceros exhibits significant biochemical changes on exposure to endosulfan,
      this species could possibly be used as biosensor of coastal marine and estuarine
      pollution by OCs.

PMID- 19846201
TI  - Effects of metals on feeding rate and digestive enzymes in Gammarus fossarum: an
      in situ experiment.
AB  - The feeding activity and afterward the assimilation of the products resulting of
      the food digestion, allow organisms to obtain energy useful for growth,
      maintenance and reproduction. These biological parameters may be studied to
      assess the impact of contaminants on the energy metabolism of organisms, which
      could induce potential effects at an individual level. The studied species was an
      amphipod Gammarus fossarum, which has a high ecological relevance since it is
      widespread in European streams and plays a major role in the breakdown of leaf
      litter. Thus some G. fossarum were transplanted in four sites of a river
      characterized by metal contamination (Amous River, France). The following
      parameters were studied: digestive enzymes activities (esterase, beta
      glucosidase, beta-galactosidase, amylase and endoglucanase), feeding rate, metal
      bioaccumulation and survival. Results showed a strong relationship between
      digestive enzymes activities, feeding rate and metal contents.

PMID- 19846202
TI  - Treatment of chloramphenicol-contaminated soil by microwave radiation.
AB  - This paper describes the microwave (MW) treatment of soil contaminated by
      chloramphenicol (CAP), using granular activated carbon (GAC) as MW absorbent. It
      was found that the addition of GAC effectively increased the temperature of soil.
      Large MW power and GAC dosage were beneficial for a completed decomposition of
      CAP. The effect of initial CAP concentration on decomposition was minute and a
      small scale of soil/GAC was disadvantageous. The degradation mechanism by MW
      radiation was also explored. The decomposition product of 4-nitrobenzoic acid
      after MW radiation was confirmed by LC-MS. The analysis by GC-MS and FTIR proved
      that parts of the decomposed fragment of CAP reacted with soil organic matters
      and formed compounds with larger molecular weight than CAP, but the concentration
      of each product was extremely low. It was suggested that MW radiation was an
      alternative technology for the treatment of antibiotics-contaminated soils.

PMID- 19846203
TI  - Occurrence and diurnal variation of polychlorinated biphenyls and polybrominated
      diphenyl ethers in the background atmosphere of Eastern Mediterranean.
AB  - During a two-week intensive field campaign conducted at a background location of
      the Eastern Mediterranean, consecutive 10-h air samples were collected under
      intense photochemical conditions and analyzed for polychlorinated biphenyls
      (PCBs) and polybrominated diphenyl ethers (PBDEs). The average gas-phase
      concentration of total PCBs and PBDEs was 73+/-29 and 3.9+/-2.1 pg m(-3),
      respectively. The study of Clausius-Clapeyron plots and air mass back
      trajectories assigned the origin of air masses as the factor largely controlling
      the variation of PCB and PBDE air concentrations in the study area. Using
      principal component analysis, discrete differences in PCBs homologue profiles
      were revealed between day and night samples and attributed to the daytime
      reaction with hydroxyl radicals. In contrast, PBDE homologue profiles did not
      show any characteristic day-to-night shifts that could be attributed to hydroxyl
      radical reaction or photolysis.

PMID- 19846204
TI  - The partition behavior of tributyltin and prediction of environmental fate,
      persistence and toxicity in aquatic environments.
AB  - Tributyltin (TBT) is one of the most toxic anthropogenic compounds introduced
      into the aquatic environment. It has a relatively high affinity for particulate
      matter, providing a direct and potentially persistence route of entry into
      benthic sediments. To understand TBT behavior, computational programs are an
      exceptionally helpful tool for modeling and prediction. EPISuite program was used
      for evaluation of the prediction data including fate, persistence and toxicity
      from the partition coefficient values. Without experimental data, the model is
      useful for prediction but is essentially a default model. A site specific
      assessment is possible by measuring the partition coefficients and entering the
      experimental values obtained into the model. This paper describes the results of
      a study undertaken to determine the partition coefficients and the effect of
      various parameters on such partition coefficients. The octanol-water partition
      coefficient (K(ow)) was determined by the OECD shake-flask method, with the
      logarithm values obtained ranging from 3.9 to 4.9 depending on salinity. The
      sediment-water partition coefficient (K(d)) was determined by ASTM method of
      generating Freundlich adsorption isotherms, the obtained values ranged from 88 to
      4909 L kg(-1) depending on sediment properties, salinity, pH, and temperature.
      The experimental partition coefficient K(ow) and K(oc) (calculated from K(d))
      were used as input data into the prediction program to provide accurate values
      for the natural samples in situ. The experimental prediction showed lower
      toxicity than the default model, but represent actual toxicity and accumulation
      at the natural site. Moreover, the environmental fate was significantly different
      when the experimental values and the default values were compared.

PMID- 19846205
TI  - In search of the main properties of phthalocyanines participating in toxicity
      against cyanobacteria.
AB  - Phthalocyanines are promising photosensitizers for use in various branches of
      science including nanotechnology. In the presence of visible light and diatomic
      oxygen, phthalocyanines can react to produce singlet oxygen (1O2*), which has
      known inhibitory effects on cellular growth and metabolic activity, although
      other mechanisms may be involved. The present work focuses on the properties of
      phthalocyanines (atom charge densities, singlet oxygen production, inhibition
      effects at various irradiances) contributing to toxicity against the
      cyanobacteria, Synechococcus nidulans. Our results indicate that positive charge
      densities at peripheral parts of substituents exhibit greater inhibitory effects
      against S. nidulans than the amount of singlet oxygen produced, potentially by
      binding to negatively charged membranes on the cell surface. The weak effect of
      1O2* was further demonstrated by a 10% increase in phthalocyanine toxicity (the
      maximal inhibition detected) when the irradiance increased 3-fold from 1200 to
      4000 lux.

PMID- 19846206
TI  - QSAR analysis on Spodoptera litura antifeedant activities for flavone
      derivatives.
AB  - We establish useful models that relate experimentally measured biological
      activities of compounds to their molecular structure. The pED(50) feeding
      inhibition on Spodoptera litura species exhibited by aurones, chromones, 3
      coumarones and flavones is analyzed in this work through the hypothesis
      encompassed in the Quantitative Structure-Activity Relationships (QSAR) Theory.
      This constitutes a first necessary computationally based step during the design
      of more bio-friendly repellents that could lead to insights for improving the
      insecticidal activities of the investigated compounds. After optimizing the
      molecular structure of each furane and pyrane benzoderivative with the
      semiempirical molecular orbitals method PM3, more than a thousand of
      constitutional, topological, geometrical and electronic descriptors are
      calculated and multiparametric linear regression models are established on the
      antifeedant potencies. The feature selection method employed in this study is the
      Replacement Method, which has proven to be successful in previous analyzes. We
      establish the QSAR both for the complete molecular set of compounds and also for
      each chemical class, so that acceptably describing the variation of the
      inhibitory activities from the knowledge of their structure and thus achieving
      useful predictive results. The main interest of developing trustful QSAR models
      is that these enable the prediction of compounds having no experimentally
      measured activities for any reason. Therefore, the structure-activity
      relationships are further employed for investigating the antifeedant activity on
      previously synthesized 2-,7-substituted benzopyranes, which do not pose any
      measured values on the biological expression. One of them, 2-(alpha-naphtyl)-4H-1
      benzopyran-4-one, results in a promising structure to be experimentally analyzed
      as it has predicted pED(50)=1.162.

PMID- 19846207
TI  - E-waste: an assessment of global production and environmental impacts.
AB  - E-waste comprises discarded electronic appliances, of which computers and mobile
      telephones are disproportionately abundant because of their short lifespan. The
      current global production of E-waste is estimated to be 20-25 million tonnes per
      year, with most E-waste being produced in Europe, the United States and
      Australasia. China, Eastern Europe and Latin America will become major E-waste
      producers in the next ten years. Miniaturisation and the development of more
      efficient cloud computing networks, where computing services are delivered over
      the internet from remote locations, may offset the increase in E-waste production
      from global economic growth and the development of pervasive new technologies. E
      waste contains valuable metals (Cu, platinum group) as well as potential
      environmental contaminants, especially Pb, Sb, Hg, Cd, Ni, polybrominated
      diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs). Burning E-waste
      may generate dioxins, furans, polycyclic aromatic hydrocarbons (PAHs),
      polyhalogenated aromatic hydrocarbons (PHAHs), and hydrogen chloride. The
      chemical composition of E-waste changes with the development of new technologies
      and pressure from environmental organisations on electronics companies to find
      alternatives to environmentally damaging materials. Most E-waste is disposed in
      landfills. Effective reprocessing technology, which recovers the valuable
      materials with minimal environmental impact, is expensive. Consequently, although
      illegal under the Basel Convention, rich countries export an unknown quantity of
      E-waste to poor countries, where recycling techniques include burning and
      dissolution in strong acids with few measures to protect human health and the
      environment. Such reprocessing initially results in extreme localised
      contamination followed by migration of the contaminants into receiving waters and
      food chains. E-waste workers suffer negative health effects through skin contact
      and inhalation, while the wider community are exposed to the contaminants through
      smoke, dust, drinking water and food. There is evidence that E-waste associated
      contaminants may be present in some agricultural or manufactured products for
      export.

PMID- 19846208
TI  - Changes in the non-protein thiol pool and production of dissolved gaseous mercury
      in the marine diatom Thalassiosira weissflogii under mercury exposure.
AB  - Two detoxification mechanisms working in the marine diatom Thalassiosira
      weissflogii to cope with mercury toxicity were investigated. Initially, the
      effect of mercury on the intracellular pool of non-protein thiols was studied in
      exponentially growing cultures exposed to sub-toxic HgCl(2) concentrations. T.
      weissflogii cells responded by synthesizing metal-binding peptides, named
      phytochelatins (PCs), besides increasing the intracellular pool of glutathione
      and gamma-glutamylcysteine (gamma-EC). Intracellular Hg and PC concentrations
      increased with the Hg concentration in the culture medium, exhibiting a distinct
      dose-response relationship. However, considerations of the PCs-SH:Hg molar ratio
      suggest that glutathione could also be involved in the intracellular mercury
      sequestration. The time course of the non-protein thiol pool and Hg intracellular
      concentration shows that PCs, glutathione and gamma-EC represent a rapid cellular
      response to mercury, although their role in Hg detoxification seems to lose
      importance at longer incubation times. The occurrence of a process of reduction
      of Hg(II) to Hg degrees and subsequent production of dissolved gaseous mercury
      (DGM) was also investigated at lower Hg concentrations, at which the PC synthesis
      doesn't seem to be involved. The significant (P<0.01) correlation between the
      cellular density in solution and the production of DGM suggests that this diatom
      is capable of directly producing DGM, both in light and dark conditions. This
      finding has been confirmed by the absence of DGM production in the culture media
      containing formaldehyde-killed cells. Finally, the relationship between these two
      different pathways of Hg detoxification is discussed.

PMID- 19846209
TI  - Emissions in the exhaust of fishing boats after adding viscous agents into fuel
      oils.
AB  - In order to avoid the illegal use of fishing boat fuel A (FBFA) by traveling
      diesel vehicles (TDVs) in Taiwan, alternatives that are easily distinguished from
      premium diesel fuel (PDF) were prepared to evaluate their suitability. Two new
      ingredients, pyrolysis fuel oil (PFO) and residue of desulfurization unit (RDS),
      were added into FBFA and formed PFO0.5 and RDS0.5, respectively. Along with FBFA,
      these three fuels were analyzed for their chemical and physical properties.
      Furthermore, they were used by three fishing boats with different sizes, output
      powers, and weights. The engine performances and pollutant emissions were
      examined and monitored. Experimental results show that there are significant
      differences in appearance between PDF and the two new blended fuels (PFO0.5 and
      RDS0.5), and thus misuse or illegal use of FBFA could be substantially reduced.
      The fuel consumption, which is negatively related to the heating value of fuels,
      is in order of FBFA<PFO0.5=RDS0.5. In contrast with using FBFA in the three
      fishing boats, using RDS0.5 resulted in a decrease in CO and NO(x) emissions,
      while the PM emission factors (g bhp(-1) h(-1) and g L(-1)-fuel) were reduced by
      approximately 36% and 33%, respectively. Owing to the higher total aromatic
      content in PFO0.5 and RDS0.5, total-PAH concentrations in the exhausts from the
      three fishing boats using PFO0.5 and RDS0.5 were slightly (1.2 and 1.1 times,
      respectively) higher than for those using FBFA. Nevertheless, the estimated total
      BaP(eq) from the three fishing boats using RDS0.5 was 27.5, 19.5, and 8.25% lower
      than those using FBFA. With using PFO0.5, they were totally different, at 23.5,
      2.79, and 2.58% higher. With regard to looking different to PDF, RDS0.5 is
      superior to PFO0.5, and is thus recommended as a better alternative to FBFA,
      particularly because it can help lower more emissions of CO, NO(x), PM and
      BaP(eq).

PMID- 19846210
TI  - The novel P2Y 12 antagonist AZD6140 rapidly and reversibly reduces platelet
      activation in diabetic rats.
AB  - INTRODUCTION: Excessive platelet activation fundamentally contributes to
      cardiovascular events and mortality in patients with diabetes mellitus.
      Functional resistance has been described for current antiplatelet therapies in
      broad populations that include patients with diabetes. We investigated acute and
      chronic effects of AZD6140, a reversible oral rapid-onset P2Y(12) antagonist, on
      platelet reactivity in diabetic rats. MATERIALS AND METHODS: Diabetes was induced
      by streptozotocin injection in male Wistar rats. After 4 weeks, AZD6140 was
      administered (5mg/kg by gavage) and achieved sufficient plasma levels within 30
      minutes. Platelet reactivity was determined by ADP-induced P-selectin expression,
      aggregation and adhesion on fibrinogen coated membranes under arterial flow
      conditions. RESULTS: At 0.5 hour, AZD6140 strongly reduced ADP-induced P-selectin
      surface expression, inhibited ADP-induced platelet aggregation, and significantly
      reduced platelet adhesion to fibrinogen under arterial flow conditions. Chronic
      treatment with AZD6140 (10mg/kg bid for 2 weeks, based on data obtained in the
      acute study) starting at day 14 reduced P-selectin surface expression on
      circulating platelets, indicating lower in vivo platelet activation. Platelet
      reactivity was improved 12 hours after the last dose, while basal platelet
      activity remained reduced. AZD6140 was rapidly absorbed in diabetic rats and
      inhibited platelet reactivity. Chronic treatment lowered in vivo platelet
      activation of circulating platelets. CONCLUSION: AZD6140 inhibits platelet
      reactivity in diabetic rats rapidly and reversibly. Markers of tonic platelet
      activation, which were increased in diabetic rats, were lowered to levels
      comparable to non-diabetic rats following chronic treatment with AZD6140.

PMID- 19846211
TI  - Should laparoscopy be included in the work-up of advanced ovarian cancer patients
      attempting interval debulking surgery?
AB  - OBJECTIVES: Primary: To investigate whether S-LPS could contribute to a better
      identification of patients to submit to IDS. Secondary: To identify the most
      appropriate level of laparoscopic index value (PIV) to identify inoperable
      patients in this subset of patients. METHODS: A prospective single-institutional
      study including patients with advanced ovarian/peritoneal cancer (FIGO stage IIIC
      IV) to be submitted to IDS after NACT. Patients have been considered eligible for
      surgical exploration in case of complete/partial radiological or serological
      response; stable disease if primary surgery had been performed in a different
      hospital; progressive radiological disease in the presence of serological
      response, young age, and good performance status (ECOG <1); and progressive
      serological disease with stable clinical and radiological disease. A laparoscopic
      assessment for each patient has been performed. RESULTS: Ninety-eight consecutive
      AOC patients submitted to NACT have been eligible for the study. With the
      addition of S-LPS to the RECIST criteria, a surgical exploration is performed in
      all patients and the percentage of explorative laparotomies drops to about 10%.
      The use of S-LPS after the GCIG criteria can reduce the risk of both explorative
      laparotomies from 30% to 13%, and inappropriate unexplorations from 18% to 0%.
      Moreover, at a PIV >4 the probability of optimally resecting the disease at
      laparotomy is equal to 0. CONCLUSIONS: Present data suggest that S-LPS can play a
      relevant role to discriminate patients with partially/stable disease or referred
      from other Institutions after NACT, which can be susceptible of successful IDS.

PMID- 19846213
TI  - Vaginal and neonatal skin cleansing with chlorhexidine.

PMID- 19846212
TI  - Chlorhexidine maternal-vaginal and neonate body wipes in sepsis and vertical
      transmission of pathogenic bacteria in South Africa: a randomised, controlled
      trial.
AB  - BACKGROUND: About 500,000 sepsis-related deaths per year arise in the first 3
      days of life. On the basis of results from non-randomised studies, use of vaginal
      chlorhexidine wipes during labour has been proposed as an intervention for the
      prevention of early-onset neonatal sepsis in developing countries. We therefore
      assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and
      vertical transmission of group B streptococcus. METHODS: In a trial in Soweto,
      South Africa, 8011 women (aged 12-51 years) were randomly assigned in a 1:1 ratio
      to chlorhexidine vaginal wipes or external genitalia water wipes during active
      labour, and their 8129 newborn babies were assigned to full-body (intervention
      group) or foot (control group) washes with chlorhexidine at birth, respectively.
      In a subset of mothers (n=5144), we gathered maternal lower vaginal swabs and
      neonatal skin swabs after delivery to assess colonisation with potentially
      pathogenic bacteria. Primary outcomes were neonatal sepsis in the first 3 days of
      life and vertical transmission of group B streptococcus. Analysis was by
      intention to treat. The trial is registered with ClinicalTrials.gov, number
      NCT00136370. FINDINGS: Rates of neonatal sepsis did not differ between the groups
      (chlorhexidine 141 [3%] of 4072 vs control 148 [4%] of 4057; p=0.6518). Rates of
      colonisation with group B streptococcus in newborn babies born to mothers in the
      chlorhexidine (217 [54%] of 401) and control groups (234 [55%] of 429] did not
      differ (efficacy -0.05%, 95% CI -9.5 to 7.9). INTERPRETATION: Because
      chlorhexidine intravaginal and neonatal wipes did not prevent neonatal sepsis or
      the vertical acquisition of potentially pathogenic bacteria among neonates, we
      need other interventions to reduce childhood mortality. FUNDING: US Agency for
      International Development, National Vaccine Program Office and Centers for
      Disease Control's Antimicrobial Resistance Working Group, and Bill & Melinda
      Gates Foundation.

PMID- 19846214
TI  - Remote influence of off-shore fish farm waste on Mediterranean seagrass
      (Posidonia oceanica) meadows.
AB  - The aim of this study was estimating the remote influence of waste dispersed from
      a large off-shore fish farm complex (6197 ton year(-1)) on the near-shore
      Posidonia oceanica meadow (26-27 m deep) located at a distance of 3 km.
      Measurements of isotopic nitrogen content in epiphytes and seagrass leaf tissues,
      epiphyte biomass, shoot size, herbivory pressure, shoot density and seagrass
      meadow cover, performed in this meadow (FA area) were compared with those
      obtained in an undisturbed control meadow (CA area) to evaluate: (1) the remote
      influence of waste and (2) the impact of such influence on seagrass condition. In
      addition, delta(15)N measurements in particulate organic matter of natural and
      anthropogenic origin were used in a single-isotope mixing model to elucidate the
      relative contributions of these sources to the isotopic N signal measured in
      epiphytes and leaf tissues. Total tissue N content was similar between meadow
      areas, but delta(15)N signatures were significantly higher in the FA area than in
      the CA area both in epiphytes and seagrass leaf tissues. Results from the mixing
      model, together with available information on local currents and previous
      studies, support the conclusion that the dispersion of farm wastes over large
      areas (spanning kilometres) are responsible for the elevated delta(15)N
      signatures found in the FA meadow area. Despite this, no changes in meadow
      structure were detected and only some changes at the level of seagrass community
      (epiphytes abundances and herbivores activity) could be interpreted at the light
      of nutrient-induced effects in the FA area. Results from this study indicate that
      concentrating aquaculture facilities in off-shore areas is a strategy not totally
      exempt of environmental risk on near-shore sensitive habitats such as seagrass
      meadows.

PMID- 19846215
TI  - An artificial extracellular matrix created by hepatocyte growth factor fused to
      IgG-Fc.
AB  - The design of artificial extracellular matrices (ECM) has attracted much
      attention in tissue engineering and regenerative medicine as well as in molecular
      biology research. A recombinant hepatocyte growth factor (HGF), fused to an
      immunoglobulin G (IgG) Fc region (abbreviated as AeHGF-Fc) was constructed and
      confirmed by Western blot assay. Almost similar amounts of HepG2 cells adhered to
      AeHGF-Fc-coated surface compared to collagen-coated one with large morphological
      changes. Immobilized AeHGF-Fc continuously activated Akt in HepG2 cells whereas
      Akt activation induced by soluble HGF rapidly decreased with time, indicating
      that immobilized AeHGF-Fc follows different signal transduction pathways compared
      to soluble HGF.

PMID- 19846216
TI  - Polyketal microparticles for therapeutic delivery to the lung.
AB  - Inflammation in the setting of interstitial lung disease (ILD) occurs in the
      distal alveolar spaces of the lung, which presents significant challenges for
      therapeutic delivery. The development of aerosolizable microparticles from non
      immunogenic polymers is needed to enable the clinical translation of numerous
      experimental therapeutics that require localization to the deep lung and repeated
      delivery for optimal efficacy. Polyketals (PK), a family of polymers, have
      several unique properties that make them ideal for lung delivery, specifically
      their hydrolysis into non-acidic, membrane-permeable compounds and their capacity
      to form microparticles with the aerodynamic properties needed for aerosolization.
      In this study, we tested the lung biocompatibility of microparticles created from
      a polyketal polymer, termed PK3, following intratracheal instillation in
      comparison to commonly used PLGA microparticles. We furthermore tested the
      initial efficacy of PK3 microparticles to encapsulate and effectively deliver
      active superoxide dismutase (SOD), a free radical scavenging enzyme, in a model
      of lung fibrosis. Our findings indicate that PK3 microparticles display no
      detectable level of alveolar or airway inflammation, whereas PLGA induced a small
      inflammatory response. Furthermore, SOD-loaded into PK3 microparticles maintained
      its activity upon release and, when delivered via PK3 microparticles, inhibited
      the extent of lung fibrosis.

PMID- 19846217
TI  - The characteristics and performance of a multifunctional nanoassembly system for
      the co-delivery of docetaxel and iSur-pDNA in a mouse hepatocellular carcinoma
      model.
AB  - Human hepatocellular carcinoma (HCC) is one of the most causes of cancer-related
      death and is well known because of resistant to chemotherapeutic drug. Co
      delivery of antitumor agent docetaxel and iSur-pDNA, a suppressor of metastatic
      and resistance-related protein survivin, was postulated to achieve
      synergistic/combined effect of antitumor drug and gene therapeutics. To valid
      this hypothesis, a folate-modified multifunctional nanoassembly (FNA) loading
      both docetaxel and iSur-pDNA was constructed and evaluated as a therapeutic
      approach for HCC. The FNAs were prepared with folate-modified lipid FA-PEG-DSPE
      as the target to tumor, protamine sulfate (PS) as the condenser to protect and
      enhance the nuclear transfer of iSur-pDNA, and DOPE-based lipid envelope as the
      carrier of doctaxel and PS/DNA complex to achieve their co-delivery and enhance
      internalization into hepatoma cells. FNAs showed the particle size about 200nm
      with encapsulation efficiency >90%. Blank nanoassemblies (BNAs) loading only
      reporter gene revealed higher transfection efficiency with neglectable
      cytotoxicity compared with Lipofectamine 2000, which could result from enhanced
      cellular uptake via ligand-receptor recognition and efficient nuclear delivery
      mediated by PS. Cytotoxicity of FNAs against hepatocellular carcinoma cell line
      BEL 7402 was much higher than either docetaxel or non-docetaxel FNAs (nFNAs)
      loading only iSur-pDNA, and was also superior to the combined treatment with free
      docetaxel and nFNAs. Better antitumor efficacy of FNAs with low systemic toxicity
      was also observed on mouse hepatocellular carcinoma xenograft model. These
      results suggested that co-delivery of docetaxel and iSur-pDNA with FNAs could be
      a safer and more efficient strategy for the treatment of locally advanced and
      metastatic HCC.

PMID- 19846218
TI  - Expression and regulation by PPARgamma of hCG alpha- and beta-subunits:
      comparison between villous and invasive extravillous trophoblastic cells.
AB  - During human placental development trophoblast follows two differentiation
      pathways: the extravillous (EVCT) and the villous cytotrophoblasts (VCT) that
      display different phenotypes and functions. It is well established that human
      chorionic gonadotropin hormone (hCG) is mainly secreted by the endocrine VCT
      (syncytiotrophoblast) into the maternal compartment and stimulates the formation
      of the syncytiotrophoblast (ST) in an autocrine manner. We recently reported that
      the invasive EVCT also produces hCG that promotes trophoblast invasion in vitro.
      Herein, we compared hCG gene expression in primary culture of villous and
      extravillous trophoblasts obtained from the same first trimester human chorionic
      villi and differentiated in vitro into ST and invasive EVCT, respectively. Total
      hCG, free alpha and free beta subunits were quantified in cell supernatants by
      immunometric assays and normalized to DNA content. alpha and beta transcript
      levels were quantified by Q-PCR and normalized to cytokeratin 7. We show that
      free alpha-, free beta-subunits and total hCG are differently expressed and
      secreted by the two trophoblast subtypes during their differentiation in vitro.
      We found an alpha/beta ratio 100 times lower in invasive EVCT in comparison to
      the ST suggesting that beta subunit may not be step limiting for hCG production
      in EVCT. Finally we investigated the regulation of hCG gene expression by
      PPARgamma, a nuclear receptor that controls trophoblast differentiation and
      invasion. Interestingly, activation of PPARgamma by the agonist rosiglitazone
      gave opposite results in the endocrine VCT and invasive EVCT: alpha and beta
      subunit transcript levels and protein secretions were up regulated in VCT,
      whereas they were down regulated in EVCT. Our results demonstrated that hCG gene
      expression is differentially regulated in the two trophoblast lineages during
      their in vitro differentiation and modulated in an opposite way by PPARgamma.

PMID- 19846219
TI  - Guest editorial for the special issue peptide receptors: focus on neuropeptides
      and kinins.

PMID- 19846220
TI  - Molecular basis of allergen cross-reactivity: non-specific lipid transfer
      proteins from wheat flour and peach fruit as models.
AB  - Peach non-specific lipid transfer protein (Pru p 3; nsLTP) has been characterized
      as the major food allergen in the adult Mediterranean population. Its wheat
      homologous protein, Tri a 14 has a relevant inhalant allergen in occupational
      baker's asthma. Different sensitization patterns to these allergens have been
      found in patients with this latter disorder. The objective of the present study
      was to characterize IgE epitopes of Tri a 14 and to compare them with those of
      Pru p 3 using three complementary strategies: the analysis of IgE-binding
      capacity of decapeptides bound to membrane, the identification of mimotopes using
      a phage display random peptide library, and the analysis of the surface
      electrostatic potential of both allergens. Thus, synthetic overlapping
      decapeptides, covering the Pru p 3 and Tri a 14 amino acid sequences, were used
      to identify sequential regions involved in recognition of IgE from baker's asthma
      patients sensitized to both nsLTPs. A phage display library was screened with
      total IgE from the same patients, and positive clones sequentially selected using
      the purified allergens, allowed to identify mimotopes (conformational epitopes)
      of Tri a 14 and Pru p 3. Both sequential regions and mimotopes were localized in
      the corresponding 3D molecular surface and their electrostatic properties were
      analyzed. Common sequential regions with strong IgE-binding capacity (residues 31
      40 and 71-80) were identified in Tri a 14 and Pru p 3, whereas regions Tri a
      14(51-60) and Pru p 3(11-20) were found specific of each allergen. A major
      conformational epitope (mimotope), L34H35N36R39S40S42D43G74V75L77P78Y79T80, which
      comprised the two common sequential epitopes, was located in Tri a 14, and a very
      similar one in Pru p 3. However, differences were detected on the surface
      electrostatic potential of both mimotopes: a first part (around residues 31-45)
      showed similar positive features in both allergens, whereas a second part (around
      residues 74-80) was markedly negative in Tri a 14 but neutral-positive in Pru p
      3. Tri a 14 and Pru p 3 have a similar conformational region involved in IgE
      binding, although their electrostatic features are different. Additionally,
      common and specific sequential IgE-binding regions were mapped in both allergens.
      These findings could be instrumental in understanding the cross-reactivity and
      specificity of sensitization to both homologous allergens.

PMID- 19846221
TI  - Brain morphology of patients with body dysmorphic disorder.
AB  - BACKGROUND: There has been dearth of investigations concerning morphometric
      magnetic resonance imaging (MRI) study of regional brain volumes in body
      dysmorphic disorder (BDD). So we performed a volumetric MRI study in patients
      with BDD focusing on the in vivo neuroanatomy of thalamus, caudate nucleus,
      anterior cingulate cortex, and orbito-frontal cortex (OFC) concurrently. METHODS:
      The whole brain, total gray and white matter volume, thalamus, caudate nucleus,
      anterior cingulate cortex, and OFC volumes were blindly measured in 12
      unmedicated male BDD patients not having any comorbidity and 12 male control
      subjects matched for age, and gender. RESULTS: The mean OFC and anterior
      cingulate volumes were significantly smaller than those of healthy controls. The
      mean white matter volume was larger than that of controls. There was a trend
      toward increased thalamic volume in patients compared with that of control
      subjects. Length of illness was inversely correlated with OFC volumes in the
      patient group both on the left and right sides. CONCLUSIONS: These findings may
      be interpreted as further evidence for the inclusion of BDD among a group of
      obsessive-compulsive spectrum disorders. Future research is necessary to confirm
      these preliminary findings, to extend them, and to clarify their significance
      with respect to the etiology and pathophysiology of BDD.

PMID- 19846222
TI  - Prevalence of habitual snoring and symptoms of sleep-disordered breathing in
      adolescents.
AB  - OBJECTIVE: Sleep-disordered breathing is an important public health problem in
      adolescents. The aim of this study was to investigate the prevalence and risk
      factors of habitual snoring and symptoms of sleep-disordered breathing in
      adolescents. METHODS: A cross-sectional study was conducted with children from
      primary schools and high schools that the ages ranged from 12 to 17 years. Data
      were collected by physical examination and questionnaires filled in by parents
      regarding sleep habits and possible risk factors of snoring. According to
      answers, children were classified into three groups: non-snorers, occasional
      snorers, and habitual snorers. RESULTS: The response rate was 79.2%; 1030 of 1300
      questionnaires were fully completed and analyzed. The prevalence of habitual
      snoring was 4.0%. Habitual snorers had significantly more nighttime symptoms
      including observed apneas, difficulty breathing, restless sleep and mouth
      breathing during sleep compared to occasional and non-snorers. Prevalence of
      habitual snoring was increased in children who had had tonsillar hypertrophy,
      allergic rhinitis, and maternal smoking. CONCLUSION: We found the prevalence of
      habitual snoring to be 4.0% in adolescents from the province of Manisa, Turkey
      which is low compared to previous studies. Habitual snoring is an important
      problem in adolescents and habitual snorers had significantly more nighttime
      symptoms of sleep-disordered breathing compared to non-snorers.

PMID- 19846223
TI  - Nickel dynamics in the lakewater metal biomonitor Chaoborus.
AB  - Nickel (Ni) is a widespread contaminant present at toxic concentrations in
      aquatic systems in the vicinity of some mining and smelting operations. However,
      its accumulation by aquatic animals has been little studied and there are few
      biomonitors for this metal. Recently, larvae of the aquatic insect Chaoborus were
      shown to be effective as biomonitors for Ni concentrations in lakewater. Since
      animals are more effective as biomonitors when we understand how they take up
      their contaminants (from water or from food) and the rate at which they exchange
      contaminants with their surroundings, we set out to measure these parameters for
      Chaoborus. To achieve these goals, we exposed the components of a laboratory food
      chain (green alga, cladoceran, Chaoborus) to realistic Ni concentrations. We
      found that the majority ( approximately 65%) of the Ni taken up by Chaoborus
      flavicans comes from lakewater, with the remainder coming from its planktonic
      prey (Daphnia magna). This result is consistent with the low mean efficiency
      (14%) with which C. flavicans assimilated Ni from its prey. To explain the low
      efficiency of Ni uptake from food we measured the subcellular distribution of Ni
      in prey, which predicted that the majority of the Ni in prey ( approximately 55%)
      was available for assimilation by the predator. This potential Ni uptake
      efficiency was only reached in animals that ingested few prey, likely because
      their gut passage time was longer than those ingesting many prey. We also
      measured Ni uptake and loss by C. flavicans exposed to Ni in water then used
      these data to parameterize a mechanistic bioaccumulation model that allowed us to
      describe Ni exchange between this insect and water. Lastly, we used these model
      constants, along with field measurements of Ni in 10 Canadian lakes, to predict
      Ni concentrations in field populations of Chaoborus. Model predictions
      overestimated Ni concentrations in field populations by a factor of 4. We suggest
      that uncertainties in the rate constant for Ni uptake from water and a lack of
      measured Ni concentrations in the prey eaten by Chaoborus larvae in the field
      could explain this difference.

PMID- 19846224
TI  - Adult age differences in the Color Stroop Test: a comparison between an Item-by
      item and a Blocked version.
AB  - The Color Stroop Test is consensually considered as a task to assess the
      efficiency of inhibitory mechanisms. If the Stroop interference effect is largely
      undisputed, it is also acknowledged that the size of this effect varies as a
      function of various task manipulations, such as the task format. The aim of the
      present study was to compare the size of adult age-related differences in
      inhibition as assessed by two different versions of the Color Stroop Test: a
      standard Blocked paper-and-pencil version and a computerized Item-by-item one.
      Results showed pronounced age-related differences in the interference effect in
      the Blocked version, but not in the Item-by-item one. These findings are
      discussed in terms of the characteristics of the tasks. The choice of the
      appropriate version with respect to clinical aims is also addressed.

PMID- 19846225
TI  - Knowledge and perceptions of dog-associated zoonoses: Brazos County, Texas, USA.
AB  - In order to assess the knowledge and perceptions of dog-associated zoonoses in
      Brazos County, Texas, random digit dialing was used to select 922 households for
      participation in a cross-sectional telephone survey. The interviews were
      completed during June 2008 and yielded a response rate of 55% (922/1691). Fifty
      six percent of the respondents who completed the questionnaire owned dogs. Eighty
      six percent of the respondents indicated they would report being bitten by a dog
      that they did not own. Five factors were shown to be significantly associated
      with such reporting. Those respondents who believed that rabies could be
      transmitted by bats were 5.5 times more likely (95% CI: 1.6, 18.6) to report a
      dog bite compared to people who did not hold this belief. Respondents who would
      seek emergency treatment if they believed they had been exposed to rabies were
      3.1 times more likely to report a bite (95% CI: 1.8, 5.4). Those who were over 60
      years of age were 2.3 times more likely (95% CI: 1.2, 4.4) to report being bitten
      when compared to respondents who were under the age of 60. Living inside the city
      limits also increased the chance that the respondent would report being bitten by
      a dog (OR 2.3, 95% CI: 1.4, 3.9). Females were 2.3 times more likely (95% CI:
      1.3, 3.7) to report being bitten than their male counterparts. Dog ownership did
      not have a significant impact on reporting. Only 85% of respondents stated that
      they would seek emergency treatment if they believed that they may have been
      exposed to rabies. In addition, only 59% of respondents were aware that exposure
      to rabies without treatment could lead to death. While 98% of respondents had
      heard of rabies and knew that it was possible to get it from a dog, only 54% of
      respondents knew that worms could be transmitted from dogs to people. This study
      demonstrated that many people surveyed lacked knowledge about dog-associated
      zoonotic diseases, which could seriously impact their health and the health of
      their families. It is important to find a method of getting information out to
      the public in order to correct this deficiency.

PMID- 19846226
TI  - Farm husbandry and badger behaviour: opportunities to manage badger to cattle
      transmission of Mycobacterium bovis?
AB  - Bovine tuberculosis (bTB) is a serious disease of cattle in the UK in terms of
      the economic impact on the farming industry. The disease has proven difficult to
      control in the cattle population and the Eurasian badger (Meles meles) is a
      source of infection. In recent years, there has been growing interest in the
      potential to employ farm husbandry and biosecurity practices to reduce bTB
      transmission risks. Here we review the potential routes of bTB transmission
      between badgers and cattle and explore the options for managing cattle and badger
      behaviour with a view to reducing the risks of inter-species transmission at
      pasture and within farm buildings. We discuss the relative merits of different
      cattle grazing regimes, habitat manipulations and badger latrine management in
      reducing the potential for badger-cattle contact at pasture. The physical
      exclusion of badgers from farm buildings is suggested as the simplest, and
      potentially most effective, method of reducing contact and opportunities for
      disease transmission between badgers and cattle. However, more research is
      required on the effectiveness, practicalities and costs of implementing such
      measures before specific guidance can be developed.

PMID- 19846227
TI  - Waiting-time targets in the healthcare sector: how long are we waiting?
AB  - Waiting-time targets are used by policy makers to monitor providers' performance.
      Such targets are based on the distribution of the patients on the list. We
      compare and link such distribution with the distribution of waiting time of
      patients treated, as opposed to on the list, which is a better measure of total
      disutility from waiting (although can only be calculated retrospectively). We
      show that the latter can be calculated from the former, and vice versa. We also
      show that, depending on how the hazard rate varies with time waited, the
      proportion of patients on the list waiting more than x periods can be higher or
      lower than the proportion of patients treated waiting more than x periods.
      However, empirically we find that the proportion of patients waiting on the list
      more than x months is smaller than our estimate of the proportion of patients
      treated waiting more than x months.

PMID- 19846228
TI  - Follow-on protein products: scientific issues, developments and challenges.
AB  - Scientific and regulatory issues around approval of follow-on protein products,
      referred to as biosimilars in Europe, have been a topic of great interest and
      debate recently. The central issue is our limited understanding of how the
      different quality attributes of a product have an impact on its safety and
      efficacy. Crucial gaps in our knowledge include a lack of standardization in the
      way in which data are collected, analyzed and reported, and limitations in the
      ability of non-clinical tools for predicting clinical safety and efficacy.
      Complexity of protein products with respect to the numerous quality attributes
      and complexity of the biotechnology processes and the raw materials add to the
      challenges. In this paper, recommendations are presented to help at least
      partially alleviate these challenges.

PMID- 19846229
TI  - ExacTrac X-ray 6 degree-of-freedom image-guidance for intracranial non-invasive
      stereotactic radiotherapy: comparison with kilo-voltage cone-beam CT.
AB  - BACKGROUND AND PURPOSE: To compare the residual setup errors measured with
      ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT)
      for a head phantom and patients receiving intracranial non-invasive fractionated
      stereotactic radiotherapy (SRT). MATERIALS AND METHODS: Setup data were collected
      on a Novalis Tx treatment unit for an anthropomorphic head phantom and 18
      patients with intracranial tumors. Initial corrections were determined and
      corrected with the ExacTrac system only, and then the residual setup error was
      determined by means of three different procedures. These procedures included
      registrations of ExacTrac X-ray images with the corresponding digitally
      reconstructed radiographs (DRRs) using the ExacTrac 6D fusion, and registrations
      of CBCT images with the planning CT using both online 3D fusion and offline 6D
      fusion. The difference in residual setup errors between ExacTrac system and CBCT
      was computed. The impact of rotations on the difference was evaluated. RESULTS: A
      modest difference in residual setup errors was found between ExacTrac system and
      CBCT. The root-mean-square (RMS) of the differences observed for translations was
      typically <0.5mm for phantom, and <1.5mm for patients, respectively. The RMS of
      the differences for rotation(s) was however <0.2 degree for phantom, and <1.0
      degree for patients, respectively. The impact of rotation on the setup difference
      was minor but not negligible. CONCLUSIONS: This study indicates that there is a
      general agreement between ExacTrac system and CBCT.

PMID- 19846230
TI  - New inverse planning technology for image-guided cervical cancer brachytherapy:
      description and evaluation within a clinical frame.
AB  - PURPOSE: To test the feasibility of a new inverse planning technology based on
      the Hybrid Inverse treatment Planning and Optimisation (HIPO) algorithm for image
      guided cervical cancer brachytherapy in comparison to conventional manual
      optimisation as applied in recent clinical practice based on long-term
      intracavitary cervical cancer brachytherapy experience. MATERIALS AND METHODS:
      The clinically applied treatment plans of 10 tandem/ring (T/R) and 10 cases with
      additional needles (T/R+N) planned with PLATO v14.3 were included. Standard
      loading patterns were manually optimised to reach an optimal coverage with 7 Gy
      per fraction to the High Risk CTV and to fulfil dose constraints for organs at
      risk. For each of these patients an inverse plan was retrospectively created with
      Oncentra GYN v0.9.14. Anatomy based automatic source activation was based on the
      topography of target and organs. The HIPO algorithm included individual gradient
      and modification restrictions for the T/R and needle dwell times to preserve the
      spatial high-dose distribution as known from the long-term clinical experience in
      the standard cervical cancer brachytherapy and with manual planning. RESULTS:
      HIPO could achieve a better target coverage (V100) for all T/R and 7 T/R+N
      patients. Changes in the shape of the overdose volume (V200/400) were limited.
      The D(2 cc) per fraction for bladder, rectum and sigmoid colon was on average
      lower by 0.2 Gy, 0.4 Gy, 0.2 Gy, respectively, for T/R patients and 0.6 Gy, 0.3
      Gy, 0.3 Gy for T/R+N patients (a decrease from 4.5 to 4 Gy per fraction means a
      total dose reduction of 5 Gy EQD2 for a 4-fraction schedule). In general the
      dwell times in the additional needles were lower compared to manual planning. The
      sparing factors were always better for HIPO plans. Additionally, in 7 T/R and 7
      T/R+N patients all three D(0.1 cc), D(1 cc) and D(2 cc) for vagina wall were
      lower and a smaller area of vagina was covered by the reference dose in HIPO
      plans. Overall loading times in the tandem, the ring and the needles, as well as
      dose distribution, were largely preserved with adaptations performed due to
      specific topographical variations, in particular in lateral and caudal
      directions. CONCLUSIONS: Inverse planning based on the HIPO algorithm can produce
      treatment plans for cervical cancer brachytherapy which are comparable to plans
      based on manual optimisation as applied in clinical practice. It is essential to
      take into account the spatial dose distribution in addition to the DVH-based
      constraints. The proposed inverse planning concept is feasible for improving the
      therapeutic ratio and limiting substantial high-dose regions around needles.

PMID- 19846231
TI  - Risk factors for voice quality after radiotherapy for early glottic cancer.
AB  - BACKGROUND AND PURPOSE: In the majority of patients irradiated for early glottic
      cancer an abnormal voice was reported. The purpose of the study was to determine
      the factors influencing voice quality after radiotherapy for T1 glottic cancer.
      METHODS: The voices of 75 male patients irradiated for T1 glottic carcinoma were
      assessed subjectively and objectively by acoustic analyses and aerodynamic
      measurements. The laryngeal function and morphology were evaluated by
      videolaryngostroboscopy. The data on smoking habits, the associated diseases
      influencing voice quality, the extent of the tumor, the type of biopsy, and the
      irradiation technique were collected from the medical records. The data on the
      factors influencing voice quality were compared for patients with a normal/near
      normal voice and those with a hoarse voice. RESULTS: Voice quality was at least
      slightly abnormal in 94.7% and 81.3% of patients, when assessed perceptively and
      objectively, respectively. Smoking after the completed treatment, more severe
      morphologic alterations of the vocal folds, dryness of the throat, incomplete
      closure of the vocal folds and functional voice disorders expressed as
      supraglottic activity adversely influenced the voice quality. A good correlation
      between the perceptive voice assessment and the acoustic analyses was
      established. CONCLUSIONS: After the successful irradiation for T1 glottic
      carcinoma, the great majority of the patients have at least a slightly hoarse
      voice. A better voice outcome could be achieved if radiotherapy was followed by
      the patient's cessation of smoking and the appropriate voice therapy.

PMID- 19846232
TI  - Motor perseveration during an "A not B" task in children with intellectual
      disabilities.
AB  - This study was designed to identify perseverative reaching tendencies in children
      with intellectual disabilities (ID), over a period of 1 year, by using a version
      of the Piagetian "A not B" task modified by Smith, Thelen, Titzer, and McLin
      (1999). Nine children (4.8 years old at the beginning of the study) with
      intellectual disabilities (ID) (eight with mild ID; one with moderate ID) were
      assessed every 3 months for approximately 1 year, totaling four assessments. The
      results indicate that in a majority of the cases perseveration was resilient, and
      that the visual system decoupled from the reaching, especially towards the later
      assessment periods at the end of the year. Across assessment periods variability
      seemed to increase in each trial (A1 through B2) for reached target. These
      individuals, vulnerable to distraction and attention and to short-term memory
      deficits, are easily locked into rigid modes of motor habits. They are
      susceptible to perseveration while performing simple task contexts that are
      typically designed for 10- to 12-month-old, normally-developing infants,
      therefore creating strong confinements to stable, rigid modes of elementary forms
      of behavior.

PMID- 19846233
TI  - Inhibition of spoilage mould conidia by acetic acid and sorbic acid involves
      different modes of action, requiring modification of the classical weak-acid
      theory.
AB  - Fungal spoilage of many foods is prevented by weak-acid preservatives such as
      sorbic acid or acetic acid. We show that sorbic and acetic acids do not both
      inhibit cells by lowering of internal pH alone and that the "classical weak-acid
      theory" must be revised. The "classical weak-acid theory" suggests that all
      lipophilic acids with identical pK(a) values are equally effective as
      preservatives, causing inhibition by diffusion of molecular acids into the cell,
      dissociation, and subsequent acidification of the cytoplasm. Using a number of
      spoilage fungi from different genera, we have shown that sorbic acid was far more
      toxic than acetic acid, and no correlation existed between resistance to acetic
      acid and resistance to sorbic acid. The molar ratio of minimum inhibitory
      concentrations (MICs) (acetic: sorbic) was 58 for Paecilomyces variotii and 14
      for Aspergillus phoenicis. Using flow cytometry on germinating conidia of
      Aspergillusniger, acetic acid at pH 4.0 caused an immediate decline in the mean
      cytoplasmic pH (pH(i)) falling from neutrality to approximately pH 4.7 at the MIC
      (80 mM). Sorbic acid also caused a rapid but far smaller drop in pH(i), at the
      MIC (4.5 mM); the pH remained above pH 6.3. Over 0-5 mM, a number of other weak
      acids caused a similar fall in cytoplasmic pH. It was concluded that while acetic
      acid inhibition of A. niger conidia was due to cytoplasmic acidification,
      inhibition by sorbic acid was not. A possible membrane-mediated mode of action of
      sorbic acid is discussed.

PMID- 19846234
TI  - Validity of real time ultrasound in the diagnosis of hepatic steatosis: a
      prospective study.
AB  - BACKGROUND/AIMS: Ultrasound is used to screen for hepatic steatosis, the most
      common liver disease in the United States. However, few studies have
      prospectively evaluated the accuracy of ultrasound to diagnose hepatic steatosis.
      Therefore, a double blinded prospective study was performed in consecutive
      patients undergoing liver biopsy to evaluate the accuracy of ultrasound to
      diagnose hepatic steatosis. METHODS: Real time ultrasound was performed just
      prior to the biopsy by a single investigator masked to the clinical diagnosis.
      The liver biopsy was reviewed by a pathologist masked to the clinical indication
      or sonographic findings. RESULTS: Of 73 consecutive patients studied,
      macrovesicular steatosis of any severity on biopsy was found in 46 (63%) and
      micro vesicular fat found in 51 (69.9%). The overall impression of the
      sonographer for the presence of macrovesicular hepatic steatosis of any degree
      had a sensitivity of 60.9% and a specificity of 100%. The sensitivity increased
      to 100% and the specificity to 90% when there was > or =20% of fat. The zonular
      distribution of the fat did not alter the diagnostic accuracy of ultrasound.
      Ultrasound had a poor yield in the diagnosis of microvesicular fat with an
      overall sensitivity of 43% and a specificity of 73%. The combination of increased
      echogenicity and portal vein blurring on ultrasound had the greatest sensitivity
      in the diagnosis of hepatic steatosis. CONCLUSION: Real time ultrasound using a
      combination of sonographic findings has a high specificity but underestimates the
      prevalence of hepatic steatosis when there is<20% fat.

PMID- 19846235
TI  - Scarcity and inequity of mental health research resources in low-and-middle
      income countries: a global survey.
AB  - OBJECTIVE: To map mental health research capacity and resources in low-and-middle
      income countries (LAMIC) for the years 1993-2003. METHOD: Mental health
      researchers from 114 LAMIC in three continents were identified through their
      publications in two databases (Medline and PsycInfo) and from local grey
      literature. A questionnaire was developed and sent to authors to elicit
      information about researchers' background, available resources and details of up
      to three recent projects. RESULTS: 4208 researchers from 83 countries were
      identified through 6340 mental health indexed-publications and 3598 publications
      from the grey literature. 912 researchers from 52 countries completed the
      questionnaires. Researchers and publications were concentrated in 10% of the
      countries. Respondents reported participation in 1847 projects, most of which
      were devoted to depression and anxiety disorders, substance misuse and psychoses.
      Epidemiologic studies, social, psychological and clinical research accounted for
      80% of all projects. Two-thirds of projects had received external funding, and
      less than one-third of them were conducted in collaboration with other countries.
      CONCLUSION: Mental health research capacity is scarce and unequally distributed
      in LAMIC. Global agencies for health research as well as LAMIC with higher
      concentrations of researchers and scientific output should play a more decisive
      role in strengthening the capacity of other LAMIC enhancing South-South
      partnerships and networks.

PMID- 19846236
TI  - Hadal trenches: the ecology of the deepest places on Earth.
AB  - Hadal trenches account for the deepest 45% of the oceanic depth range and host
      active and diverse biological communities. Advances in our understanding of hadal
      community structure and function have, until recently, relied on technologies
      that were unable to document ecological information. Renewed international
      interest in exploring the deepest marine environment on Earth provides impetus to
      re-evaluate hadal community ecology. We review the abiotic and biotic
      characteristics of trenches and offer a contemporary perspective of trench
      ecology. The application of existing, rather than the generation of novel,
      ecological theory offers the best prospect of understanding deep ocean ecology.

PMID- 19846237
TI  - JAAD online. Over-the-counter scar products for postsurgical patients:
      disparities between online advertised benefits and evidence regarding efficacy.
AB  - Surgical patients frequently read about over-the-counter (OTC) scar products
      online and ask physicians for advice about product use. We summarized the
      characteristics of the 20 best-selling scar products on the Web site
      drugstore.com and reviewed the medical literature for data supporting the
      efficacy of OTC scar products used on fresh postsurgical wounds. Products had an
      average price of $16.25 (range $9.49-$59.99) and an average of 9.2 ingredients
      (range 1-29). Silicone, vitamin E, and onion extract were common ingredients.
      Although weak evidence indicates that silicone gel dressings may improve
      postsurgical scar appearance, published evidence does not support postoperative
      use of most scar products. However, many products have multiple ingredients, and
      few clinical trials assess the ingredient combinations of specific products. The
      practical information about OTC scar products and published efficacy data found
      in this review may help physicians to counsel patients about postsurgical product
      use and counter unrealistic expectations gained from online advertisements.

PMID- 19846238
TI  - Application of Huisgen (3+2) cycloaddition reaction: synthesis of 1-(2,3
      dihydrobenzofuran-2-yl-methyl [1,2,3]-triazoles and their antitubercular
      evaluations.
AB  - 1,4-Disubstituted-1,2,3-triazoles (3-27) have been synthesized by [3+2]
      cycloaddition of different 2-(azidomethyl)-dihydronaptho(benzo)furans (2a, 2b, 2c
      and 2d) with different alkynes. All the compounds were screened for
      antitubercular activity against Mycobacterium tuberculosis H37Rv. Compounds 2a,
      7, 9, 12 and 14 exhibited antitubercular activities with MIC ranging from 12.5 to
      3.12 microg/ml.

PMID- 19846239
TI  - Application of desirability-based multi(bi)-objective optimization in the design
      of selective arylpiperazine derivates for the 5-HT1A serotonin receptor.
AB  - The multiobjective optimization technique based on the desirability estimation of
      several interrelated responses (MOOP-DESIRE) has been recently applied to
      quantitative structure-activity relationship (QSAR) studies. However, the
      advantage of applying this new methodology to the study of selectivity and
      affinity to competitive targets has been little explored. We used the MOOP-DESIRE
      methodology and a variation of this, to study the arylpiperazine derivates that
      could interact with 5-HT(1A) and 5-HT(2A), serotonin receptor subtypes with the
      objective of designing more selective molecules for the 5-HT(1A) receptor. We did
      show that the model results are in agreement with the available pharmacophore
      descriptions, guaranteeing an appropriate structural correlation and proving the
      methodology, as a useful tool for the important problem of selective drug design.

PMID- 19846240
TI  - Synthesis and antioxidant properties of some novel 5H-dibenz[b,f]azepine
      derivatives in different in vitro model systems.
AB  - A series of 5H-dibenz[b,f]azepine containing different aminophenols and
      substituted aminophenols were synthesized. 3-chloro-1-(5H-dibenz[b,f]azepine
      5yl)propan-1-one (2) was obtained by N-acylation of 5H-dibenz[b,f]azepine (1)
      with 3-chloro propionyl chloride. Further base condensation with different
      aminophenols and substituted aminophenols to produce series of 5H
      dibenz[b,f]azepine containing aminophenol and substituted aminophenol (2a-e). The
      structures of newly synthesized compounds were characterized by spectral and
      elemental analysis. Their antioxidant properties were evaluated by using several
      methods: scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical,
      inhibition of lipid peroxidation using beta-carotene linoleate system, inhibition
      of human low-density lipoprotein (LDL) oxidation and reducing power. Butylated
      Hydroxy Anisole (BHA) and Ascorbic acid (AA) were used as the reference
      antioxidant compounds and also the comparative study with the synthesized
      compounds was done. Under our experimental conditions, Compound (2) showed
      negligible activity over all the antioxidant assays but 5H-dibenz[b,f]azepine
      containing different aminophenols and substituted aminophenols (2a-e) showed good
      antioxidant activities over all the methods and compounds containing substituted
      aminophenols 2e and 2d showed predominant antioxidant activities among the
      synthesized analogues.

PMID- 19846241
TI  - [Diagnosis of iatrogenic diseases].

PMID- 19846242
TI  - [Adverse drug reactions and Alzheimer disease].

PMID- 19846243
TI  - Removal of a root from the maxillary sinus using functional endoscopic sinus
      surgery.

PMID- 19846244
TI  - Affect is central to patient safety: the horror stories of young anaesthetists.
AB  - This paper analyses talk produced by twenty-four newly qualified anaesthetists.
      Data were collected from round table discussions at the Young Fellows Conference
      of the Australia and New Zealand College of Anaesthetists 2006. The talk
      consisted to an important extent of narratives about experiences of horror. The
      paper isolates three themes: the normalization of horror, the functionalisation
      of horror for pedagogic purposes, and the problematization of horror. The last
      theme provides a springboard into our argument that confronting the affect
      invested in coping with medical-clinical failure is central to enabling young
      doctors, and clinicians generally, to address and resolve such adverse events. We
      conclude that the negotiation of affect through shared or 'dialogic' narrative is
      central to enabling doctors to deal with adverse events on a personal level, and
      to enabling them at a collective level to become attentive to threats to
      patients' safety.

PMID- 19846245
TI  - Exploring patient involvement in healthcare decision making across different
      education and functional health literacy groups.
AB  - Education and health literacy potentially limit a person's ability to be involved
      in decisions about their health. Few studies, however, have explored
      understandings and experiences of involvement in decision making among patients
      varying in education and health literacy. This paper reports on a qualitative
      interview study of 73 men and women living in Sydney, Australia, with varying
      education and functional health literacy levels. Participants were recruited from
      a community sample with lower educational attainment, plus an educated sample of
      University of Sydney alumni. The transcripts were analysed using the 'Framework'
      approach, a matrix-based method of thematic analysis. We found that participants
      with different education conceptualised their involvement in decision making in
      diverse ways. Participants with higher education appeared to conceive their
      involvement as sharing the responsibility with the doctor throughout the decision
      making process. This entailed verifying the credibility of the information and
      exploring options beyond those presented in the consultation. They also viewed
      themselves as helping others in their health decisions and acting as information
      resources. In contrast, participants with lower education appeared to conceive
      their involvement in terms of consenting to an option recommended by the doctor,
      and having responsibility for the ultimate decision, to agree or disagree with
      the recommendation. They also described how relatives and friends sought
      information on their behalf and played a key role in their decisions. Both
      education groups described how aspects of the patient-practitioner relationship
      (e.g. continuity, negotiation, trust) and the practitioner's interpersonal
      communication skills influenced their involvement. Health information served a
      variety of needs for all groups (e.g. supporting psychosocial, practical and
      decision support needs). These findings have practical implications for how to
      involve patients with different education and literacy levels in decision making,
      and highlight the important role of the patient-practitioner relationship in the
      process of decision making.

PMID- 19846246
TI  - Intergroup communication between hospital doctors: implications for quality of
      patient care.
AB  - Hospitals involve a complex socio-technical health system, where communication
      failures influence the quality of patient care. Research indicates the importance
      of social identity and intergroup relationships articulated through power,
      control, status and competition. This study focused on interspecialty
      communication among doctors for patients requiring the involvement of multiple
      specialist departments. The paper reports on an interview study in Australia,
      framed by social identity and communication accommodation theories of doctors'
      experiences of managing such patients, to explore the impact of communication.
      Interviews were undertaken with 45 doctors working in a large metropolitan
      hospital, and were analysed using Leximancer (text mining software) and
      interpretation of major themes. Findings indicated that intergroup conflict is a
      central influence on communication. Contested responsibilities emerged from a
      model of care driven by single-specialty ownership of the patient, with doctors
      allowed to evade responsibility for patients over whom they had no sense of
      ownership. Counter-accommodative communication, particularly involving
      interpersonal control, appeared as important for reinforcing social identity and
      winning conflicts. Strategies to resolve intergroup conflict must address
      structural issues generating an intergroup climate and evoke interpersonal
      salience to moderate their effect.

PMID- 19846247
TI  - Responses to intimate partner violence in Kakuma refugee camp: refugee
      interactions with agency systems.
AB  - Intimate partner violence (IPV) has been recognised as a significant problem
      amongst forcibly displaced communities, and great progress has been made by the
      United Nations High Commission for Refugees (UNHCR) in responding to IPV and
      other forms of sexual and gender based violence. However, they have not always
      effectively engaged refugee communities in these activities, with potentially
      negative consequences for the health and protection of women. This study was
      conducted in Kakuma refugee camp, north-west Kenya. Eighteen focus group
      discussions were conducted with 157 refugees from various nationalities,
      including Sudanese, Somali, Ethiopian, and Congolese. They focused on the nature
      and consequences of IPV in Kakuma. The aim of this paper is to explore how
      refugees in Kakuma talk about the ways that IPV is dealt with, focusing
      particularly on the ways that community responses are said to interact with
      formal response systems established by UNHCR and its implementing partners.
      Refugees talked about using a 'hierarchy of responses' to IPV, with only
      particularly serious or intransigent cases reaching UNHCR or its implementing
      agencies. Some male refugees described being mistrustful of agency responses,
      because agencies were believed to favour women and to prioritise protecting the
      woman at all costs, even if that means separating her from the family. Whilst
      community responses to IPV might often be appropriate and helpful, the findings
      of the current study suggest that in Kakuma they do not necessarily result in the
      protection of women. Yet women in Kakuma are reported to be reluctant to report
      their cases to UNHCR and its implementing agencies. A more effective protection
      response from UNHCR might involve closer co-operation with individuals and
      structures within the refugee communities to develop a co-ordinated response to
      IPV.

PMID- 19846248
TI  - Examining lateralized semantic access using pictures.
AB  - A divided visual field (DVF) experiment examined the semantic processing
      strategies employed by the cerebral hemispheres to determine if strategies
      observed with written word stimuli generalize to other media for communicating
      semantic information. We employed picture stimuli and vary the degree of semantic
      relatedness between the picture pairs. Participants made an on-line semantic
      relatedness judgment in response to sequentially presented pictures. We found
      that when pictures are presented to the right hemisphere responses are generally
      more accurate than the left hemisphere for semantic relatedness judgments for
      picture pairs. Furthermore, consistent with earlier DVF studies employing words,
      we conclude that the RH is better at accessing or maintaining access to
      information that has a weak or more remote semantic relationship. We also found
      evidence of faster access for pictures presented to the LH in the strongly
      related condition. Overall, these results are consistent with earlier DVF word
      studies that argue that the cerebral hemispheres each play an important and
      separable role during semantic retrieval.

PMID- 19846249
TI  - Conformation and thermostability of oligonucleotide d(GGTTGGTGTGGTTGG) containing
      thiophosphoryl internucleotide bonds at different positions.
AB  - The thrombin-binding aptamer d(GGTTGGTGTGGTTGG) (TBA) is an efficient tool for
      the inhibition of thrombin function. We have studied conformations and
      thermodynamic stability of a number of modified TBA oligonucleotides containing
      thiophosphoryl substitution at different internucleotide sites. Using circular
      dichroism such modifications were found not to disrupt the antiparallel
      intramolecular quadruplex specific for TBA. Nevertheless, the presence of a
      single thiophosphoryl bond between two G-quartet planes led to a significant
      decrease in the quadruplex thermostability. On the contrary, modifications in
      each of the loop regions either stabilized an aptamer structure or did not reduce
      its stability. According to the thrombin time test, the aptamer with thio
      modifications in both TT loops (LL11) exhibits the same antithrombin efficiency
      as the original TBA. This aptamer shows better stability against DNA nuclease
      compared to that of TBA. We conclude that such thio-modification patterns are
      very promising for the design of anticoagulation agents.

PMID- 19846250
TI  - Investigation on solar photocatalytic degradation of various dyes in the presence
      of Er(3+):YAlO(3)/ZnO-TiO(2) composite.
AB  - In this work, Er(3+):YAlO(3)/ZnO-TiO(2) and ZnO-TiO(2) composites were prepared
      by the ultrasonic dispersion and liquid boiling method. In succession, they were
      then characterized by X-ray diffraction (XRD) and scanning electron microscopy
      (SEM). Acid red B as a model dye compound was degraded under solar light
      irradiation to evaluate the photocatalytic activities of the Er(3+):YAlO(3)/ZnO
      TiO(2) and ZnO-TiO(2) composites. We found that the photocatalytic activity of
      ZnO-TiO(2) composite can be enhanced by adding an appropriate amount of
      Er(3+):YAlO(3). We reviewed influencing factors, such as Er(3+):YAlO(3) content,
      heat-treated temperature and heat-treated time on the photocatalytic activity of
      the Er(3+):YAlO(3)/ZnO-TiO(2) composites. In addition, the effects of solar light
      irradiation time, dye initial concentration, Er(3+):YAlO(3)/ZnO-TiO(2) amount and
      solution acidity on the photocatalytic degradation of acid red B dye in aqueous
      solution were investigated in detail. Simultaneously, the degradation and
      comparison of other dyes such as methyl orange (MO), rhodamine B (RM-B), azo
      fuchsine (AF), congo red (CG-R) and methyl blue (MB) were also reviewed. In
      addition, we attempted to explore both the principle of possible excitation of
      Er(3+):YAlO(3)/ZnO-TiO(2) under solar light irradiation and the mechanism of
      photocatalytic degradation.

PMID- 19846251
TI  - What is the optimal treatment strategy for T1 bladder tumors?

PMID- 19846252
TI  - NOx removal from vehicle emissions by functionality surface of asphalt road.
AB  - This paper reported the potential of heterogeneous photocatalysis as an advanced
      oxidation technology for NO(x) removal from vehicle emissions by using TiO(2) as
      a photocatalyst immobilized on the surface of asphalt road. Based on asphalt road
      material porous characteristic, we utilized permeability technology to make
      asphalt nano-TiO(2) to be environmental protection materials. And then using
      scanning electron microscope, we observed the penetrating effect of TiO(2). The
      effect of surface friction, humidity and light intensity on NO(x) removal had
      been systematically investigated by the use of TiO(2) immobilized on the surface
      of asphalt road as photocatalytic environmental protection materials. In
      addition, the decontaminating effect was tested by contrast test in TiO(2)
      spraying section with non-spraying section, while the productions were used in
      road environment. Results of experiment revealed that decontaminating rate of the
      productions ranged from 6% to 12% this kind of photochemical catalysis
      environmental protection material has good environment purification function.

PMID- 19846253
TI  - Platinum and rhodium associated with the leaves of Nerium oleander L.; analytical
      method using voltammetry; assessment of air quality in the Palermo (Italy) area.
AB  - A rapid accumulation of the catalytic active noble metals in the environmental
      and biological matrices was observed and concern arose about potential
      environmental and health risks. The development of reliable analytic methods to
      measure very low Pt and Rh concentrations is required. The main purpose of this
      work was to develop a reliable method for the determination of Pt and Rh in
      environmental matrices because of inherent difficulties in using conventional
      techniques used, in particular, the ICP-OES technique. A direct determination of
      Pt using ICP-MS, for instance, is problematic, due to interfering signals. In
      this work, differential pulse voltammetry (DPV/a) and adsorptive stripping
      voltammetry (AdSV) were used for the determination of Pt and Rh in Nerium
      oleander leaves. Pt and Rh concentrations were found in the ranges 0.33-25 and
      0.40-4.6 microg/kg d.w., respectively. We carried out linear regression analysis
      between total PAH concentrations in leaves of oleander and of Quercus ilex
      measured in previous researches and the data obtained in this work. The high
      correlation coefficients were obtained; which demonstrates that oleander leaves
      can be used to establish the presence and the distribution of pollutants in a
      chosen area.

PMID- 19846254
TI  - General review of flashing jet studies.
AB  - The major concern on the management of superheated liquids, in industrial
      environments, is the large potential hazards involved in cases of any accidental
      release. There is a possibility that a violent phase change could take place
      inside the fluid released generating a flashing jet. This violent phase change
      might produce catastrophic consequences, such as explosions, fires or toxic
      exposure, in the installations and in the surroundings. The knowledge and
      understanding of the mechanisms involved in those releases become an important
      issue in the prevention of these consequences and the minimization of their
      impact. This work presents a comprehensive review of information about flashing
      processes. The review begins with a description of the single phase jet followed
      by a description of the two-phase flashing jet. The concepts and implications of
      the thermodynamic and mechanical effects on the behaviour of the jets are
      considered at the beginning of the review. Following the review is devoted to the
      classification of the different study approaches used to understand flashing
      processes in the past, highlighting various critical parameters on the behaviour
      and the hazard consequences of flashing jets. The review also contains an
      extensive compilation of experimental, theoretical and numerical data relating to
      these phenomena, which includes information on the distinct characteristics of
      the jet, since type of jet, velocity distribution, expansion angle and mass phase
      change all require individual estimation.

PMID- 19846255
TI  - Do words hurt? Brain activation during the processing of pain-related words.
AB  - Previous studies suggested that areas of the pain matrix of the human brain are
      recruited by the processing of pain-related environmental cues such as pain
      related pictures or descriptors of pain. However, it is still sketchy whether
      those activations are specific to the pain-relevance of the stimuli or simply
      reflect a general effect of negative valence or increased arousal. The present
      study investigates the neural mechanisms underlying the processing of pain
      related, negative, positive, and neutral words. Pain-related words were matched
      to negative words regarding valence and arousal, and to positive words regarding
      arousal. Sixteen healthy subjects were scanned during two tasks, imagination and
      distraction, using functional MRI. When subjects were instructed to image a
      situation associated with the word presented (imagination task), we found
      increased activation within dorsolateral prefrontal cortex (DLPFC), inferior
      patietal gyri (IPG), and precuneus when processing pain-related words compared to
      other words. However, when attention was focused on a foreground task and words
      were presented in the background (distraction task), we found a decrease in
      activation within dorsal anterior cingulum (dACC) and a relative increase in
      activation within the subgenual ventral anterior cingulum (sACC) when processing
      pain related words compared to other words. Thus, activations to pain-related
      words are strongly modulated by the attention demands of the task. Most
      remarkably, the differences in processing pain-related words compared to non-pain
      related words are specific to the pain-relevance of the words and cannot simply
      be explained by their valence or arousal.

PMID- 19846256
TI  - Gold, coal and oil.
AB  - Jared Diamond has hypothesized that guns, germs and steel account for the fate of
      human societies. Here I propose an extension of Diamond's hypothesis and put it
      in other terms and dimensions: gold, coal and oil account not only for the fate
      of human societies but also for the fate of mankind through the bodily
      accumulation of anthropogenic arsenic, an invisible weapon of mass extinction and
      evolutionary change. The background is clear; arsenic species fulfill seven
      criteria for a weapon of mass extinction and evolutionary change: (i)
      bioavailability to all living organisms; (ii) imperceptibility; (iii) acute
      toxicity; (iv) bioaccumulation and chronic toxicity; (v) adverse impact on
      reproductive fitness and reproductive outcomes and early-age development and
      growth in a wide range of microbial, plant and animal species including man; (vi)
      widespread geographical distribution, mobility and ecological persistence on a
      centennial to millennial basis and (vii) availability in necessary and sufficient
      amounts to exert evolutionarily meaningful effects. The proof is becoming
      increasingly feasible as human exploitation of gold, coal and oil deposits cause
      sustainable rises of arsenic concentrations in the biosphere. Paradoxically,
      humans are among the least arsenic-resistant organisms because humans are long
      lived, encephalized and complex social metazoans. An arsenic accumulation model
      is presented here to describe how arsenic accumulates in the human body with
      increasing age and at different provisionally safe exposure levels. Arsenic
      accumulates in the human body even at daily exposure levels which are within the
      lowest possible WHO provisional tolerance limits, yielding bodily arsenic
      concentrations which are above WHO provisional limits. Ongoing consequences of
      global scale arsenic poisoning of mankind include age-specific rises in morbidity
      and mortality followed by adaptive changes. The potential rise of successful
      forms of inborn resistance to arsenic in humans will make it certain that a
      number of other hardly won, nicely balanced human-specific adaptednesses will
      decline. These include a decline of encephalization and life-span, and
      consequentially intelligence and longevity. These changes are likely to have far
      reaching impacts on biological and cultural evolution of mankind. The only
      efficient way of reducing chronic global exposure to arsenic and avoiding further
      human losses is the inactivation of important sources of anthropogenic arsenic
      such as hard rock mining and burning of fossil fuels.

PMID- 19846257
TI  - Evidence that oocyte quality in younger women with diminished oocyte reserve is
      superior to those of women of advanced reproductive age.
AB  - Evidence is provided supporting the hypothesis that the much improved prognosis
      for younger women with diminished oocyte reserve compared to women of advanced
      reproductive age is related to a difference in mechanism for oocyte depletion.
      For younger women the majority have had destruction of certain portions of their
      ovarian tissue but the remaining spared ovarian tissue has proportionately the
      same percentage of normal follicles as their age peers. The hypothesis continues
      that some factor that is responsible for earlier development of primary to antral
      follicles persists with the early conceptus and protects it from early programmed
      cell death. Thus by natural selection most women of advanced reproductive age
      have oocytes that fertilize normally and produce normal morphologic embryos, but
      lacking this apoptosis inhibiting factor dies very early between days 6 and 12
      from fertilization.

PMID- 19846258
TI  - Comment on "the matrix metalloproteinases as pharmacological target in
      osteoarthritis: statins may be of therapeutic benefit".

PMID- 19846259
TI  - Do monoamine-synthesizing cells constitute a complex network of oxygen sensors?
AB  - Oxygen represents an essential molecule for organisms. Because of this,
      sophisticated systems of sensors have evolved to monitor oxygenation of tissues.
      We propose that monoamine-synthesizing cells represent an important part of this
      system. It is well known that the carotid body, which contains chromaffin cells,
      serves as a chemical sensor of blood oxygenation. Similarly, the activity of
      adrenal medullary chromaffin cells is increased during hypoxia. Moreover, neurons
      located in the central nervous system containing catecholamines, serotonin, and
      histamine are also sensitive to hypoxia. On the basis of this common sensitivity
      of monoamine-synthesizing cells to changes in oxygenation we propose the
      hypothesis that these cells constitute a widely distributed network of sensors
      that monitor oxygen levels. The role of monoamine-synthesizing cells in
      monitoring tissue oxygen supply during both physiological and pathological
      conditions is also discussed.

PMID- 19846260
TI  - [Post-trauma uterine prolaps in infant. A case report].
AB  - We report on one case of genital prolaps that happened after an astride fell in a
      girl aged 7-year-old. The manual reducing of the cervix followed by putting a
      blown Foley catheter n(o) 8 intravaginally for 1 week has allowed good results.
      Post-trauma uterine prolaps in infant is a rare condition supposed to be due to
      connective tissue weakness. Conservative treatment should be as possible applied
      at this age.

PMID- 19846261
TI  - Pestiviruses: how to outmaneuver your hosts.
AB  - Heterogeneity is a hallmark that encompasses all aspects of pestiviruses,
      including the genetic properties, spectrum of hosts, disease signs and virulence.
      As an additional feature, pestiviruses are found world-wide, in both domesticated
      and wild animals, which indicates that these viruses are highly successful.
      Starting with the strategy by which pestiviruses persist in their host
      population, we discuss the role virulence and attenuation play in viral
      transmission and focus on the interaction of these viruses with their hosts'
      immune systems. The most unusual feature of pestiviruses is their ability to
      infect their hosts either transiently or persistently. Persistent infection, best
      known in cattle infected with bovine viral diarrhea virus, is characterized by
      immunotolerance to the infecting viral strain. This strategy of evading from the
      adaptive immune response is unique among persistent viral infections. It obviates
      antigenic variation, as used by lentiviruses, or hiding by latency, as seen in
      herpesviruses. In addition to establishing and maintaining immunotolerance,
      bovine viral diarrhea virus also evades innate immunity during persistent
      infection. Investigations in cultured cells showed that this virus fails to
      induce interferon type-I. Moreover, while being resistant to the action of
      interferon during persistent infection in its own host cells, bovine viral
      diarrhea virus does not interfere with interferon action against unrelated
      viruses infecting these cells. This novel finding of discrimination between
      "self" and "non-self" may contribute to the good health status seen in many
      persistently infected cattle. In evolutionary terms, not globally interfering
      with a crucial first line of antiviral defence of its persistently infected hosts
      may improve the chances for bovine viral diarrhea viruses to transmit to new
      hosts.

PMID- 19846262
TI  - Stability of cocaine in formalin solution and fixed tissues.
AB  - Embalming and formalin fixation are common, and yet they can create problems for
      the forensic scientist if a drug has been the cause of death and if the only
      available specimens to be analyzed are formalin-fixed tissues. Previous studies
      have demonstrated that during fixation xenobiotics are extracted into formalin
      according to tissue and fixing solution characteristics. In some cases formalin
      can react with the analyte resulting in the production of new chemical entities.
      Regarding cocaine and its metabolites, Cingolani et al. have reported that
      formalin-fixation extracts benzoylecgonine (BE) from tissues and that BE is
      stable in the fixing solution. However, the stability and kinetic properties of
      cocaine remain so far unexplored. Our data show that in buffered formalin (pH
      7.4) cocaine is hydrolyzed to BE in agreement with a pseudo first-order reaction
      kinetic (half-life time approximately 7 days), whereas in unbuffered formalin (pH
      approximately 3.5) it is relatively stable over a period of 30 days. The analysis
      of brain and liver samples at different fixation times indicates that during
      fixation an extraction process occurs for both analytes and that the extraction
      is more efficient in the liver than in the brain, probably because of a greater
      lipophilicity of the brain tissue. In conclusion, our study demonstrates that
      formalin-fixed tissues and their fixing solutions can be used for cocaine
      analysis only if a short time period has passed since the fixation beginning. The
      rapid extraction process of cocaine into formalin and the concomitant hydrolysis
      to BE occurring in buffered formalin may prevent the identification of cocaine in
      both tissues and formalin solution already at 15-30 days after fixation.
      Moreover, the unpredictable extraction rate of both analytes, along with the
      hydrolysis of cocaine into BE significantly affects tissue concentrations, thus
      complicating the interpretation of quantitative results.

PMID- 19846263
TI  - Quantification of hydrophilic ethoxylates in polysorbate surfactants using
      diffusion H1 NMR spectroscopy.
AB  - Polysorbate surfactants (commercially available as Tween) are widely used in
      pharmaceutical, cosmetic and food products. They are generally considered as
      esters of ethoxylated sorbitan with fatty acids. Diffusion H1 NMR spectroscopy on
      a solution of polysorbate 20 in D2O revealed that only one diffusion coefficient
      was found for the fatty acyl part. Using the Stokes-Einstein equation, it became
      obvious that this diffusion behavior was caused by micelles. On the other hand,
      two significantly different diffusion coefficients were found for the methylene
      groups of ethylene oxide (EO). This indicates the presence of two distinct EO
      containing species in solution. Since the slowest diffusing EO species has the
      same diffusion coefficient as the fatty acyl part, it corresponds to the micellar
      (i.e. fatty acyl bound) ethoxylates. The diffusion coefficient of the fastest
      diffusing EO species was a factor of four larger than that of the slowly
      diffusing species and was attributed to water-soluble non-esterified ethoxylates.
      A solution of polysorbate 20 in the presence of NaOD was prepared to investigate
      if hydrolysis of the sorbitan ester could be the reason for the occurence of
      these hydrophilic ethoxylates. It was found that alkaline hydrolysis does lead to
      an increasing fraction of non-esterified ethoxylates, but is not the cause of its
      presence in untreated polysorbate samples since these species were also found in
      solutions of polyethylene glycol oleyl ether (commercially available as Brij),
      which are not susceptible to hydrolysis. Fractionation of the EO species present
      in polysorbate 20 into an amphiphilic and a hydrophilic fraction was only partly
      obtained by activated carbon adsorption. On the other hand, sequential extraction
      of aqueous polysorbate solutions by ethyl acetate and chloroform enabled a nearly
      complete fractionation. H1 NMR spectroscopy proved to be very useful since it
      allows in situ determination of the global composition of a surfactant sample, as
      well as quantification of both the amphiphilic and hydrophilic ethoxylate
      fractions via diffusion measurements.

PMID- 19846264
TI  - Development and validation of a stability-indicating RP-HPLC method for assay of
      betamethasone and estimation of its related compounds.
AB  - Betamethasone (9alpha-fluoro-16beta-methylprednisolone) is one of the members of
      the corticosteriod family of active pharmaceutical ingredient (API), which is
      widely used as an anti-inflammatory agent and also as a starting material to
      manufacture various esters of betamethasone. A stability-indicating reverse-phase
      high performance liquid chromatography (RP-HPLC) method has been developed and
      validated which can separate and accurately quantitate low levels of 26
      betamethasone related compounds. The stability-indicating capability of the
      method was demonstrated through adequate separation of all potential
      betamethasone related compounds from betamethasone and also from each other that
      are present in aged and stress degraded betamethasone stability samples.
      Chromatographic separation of betamethasone and its related compounds was
      achieved by using a gradient elution at a flow rate of 1.0mL/min on a ACE 3 C18
      column (150mmx4.6mm, 3microm particle size, 100A pore size) at 40 degrees C.
      Mobile phase A of the gradient was 0.1% methanesulfonic acid in aqueous solution
      and mobile phase B was a mixture of tert-butanol and 1,4-dioxane (7:93, v/v). UV
      detection at 254nm was employed to monitor the analytes. For betamethasone 21
      aldehyde, the QL and DL were 0.02% and 0.01% respectively. For betamethasone and
      the rest of the betamethasone related compounds, the QL and DL were 0.05% and
      0.02%. The precision of betamethasone assay is 0.6% and the accuracy of
      betamethasone assay ranged from 98.1% to 99.9%.

PMID- 19846265
TI  - Evaluation of rapid diagnostic tests for malaria case management in Gabon.
AB  - A laboratory-confirmed diagnosis is the basis of malaria case management. Rapid
      diagnostic tests (RDTs) create new opportunities for improved care in endemic
      areas. Diagnostic performance of OptiMAL-IT and Acon was assessed in comparison
      with microscopy at 2 sites in Gabon. Between February 2008 and January 2009, 2125
      febrile children under 11 years old were diagnosed using microscopy and RDTs.
      Plasmodial infection was detected more frequently using Acon (27%) and OptiMAL-IT
      (27%) compared to microscopy (20%) (P < 0.01). Among the samples diagnosed
      positive by OptiMAL-IT, 78% were infected by Plasmodium falciparum, whereas 99%
      of positive blood smears were P. falciparum infections, 0.5% Plasmodium malariae,
      and 0.5% Plasmodium ovale. Both RDTs had similar sensitivity (Se) (94.0%; 95%
      confidence interval [CI], 92-96), which varied depending on the site. When
      parasite density was >100 p/microL, the Se of the 2 tests was >98% (95% CI, 96
      100). Likewise, the negative predictive values were high and comparable (>98%).
      Overtreatment with antimalarial drugs was 12%. These tests should be considered
      as a good alternative to microscopy, allowing not only an efficient and rapid
      diagnosis of malaria in primary health facilities but also to aid in promoting
      changes for antimalarial prescription behavior.

PMID- 19846266
TI  - Treatment of portal venous gas embolism with hyperbaric oxygen after accidental
      ingestion of hydrogen peroxide: a case report and review of the literature.
AB  - BACKGROUND: It is well known that hydrogen peroxide ingestion can cause gas
      embolism. OBJECTIVE: To report a case illustrating that the definitive, most
      effective treatment for gas embolism is hyperbaric oxygen therapy. CASE REPORT:
      We present a case of a woman who presented to the Emergency Department with acute
      abdominal pain after an accidental ingestion of concentrated hydrogen peroxide.
      Complete recovery from her symptoms occurred quickly with hyperbaric oxygen
      therapy. CONCLUSION: This is a case report of the successful use of hyperbaric
      oxygen therapy to treat portal venous gas embolism caused by hydrogen peroxide
      ingestion. Hyperbaric oxygen therapy can be considered for the treatment of
      symptomatic hydrogen peroxide ingestion.

PMID- 19846267
TI  - Do either corticosteroids or antiviral agents reduce the risk of long-term facial
      paresis in patients with new-onset Bell's palsy?
AB  - BACKGROUND: The cause of Bell's palsy remains uncertain, although accumulating
      evidence suggests a viral etiology. To date, treatment to minimize long-term
      deficits from this disorder typically includes anti-inflammatory or antiviral
      medication. CLINICAL QUESTION: Do corticosteroids or antiviral agents, either
      alone or in combination, reduce the risk of long-term facial paresis in patients
      with new-onset Bell's palsy? EVIDENCE REVIEW: Three multicenter, randomized,
      controlled trials enrolled over 1,500 adult patients with paroxysmal, unilateral
      paresis of cranial nerve VII and treated them with varying regimens and
      combinations of prednisolone, antiviral agents, and placebo, and evaluated
      complete recovery up to 12 months later. RESULTS: The two larger, most recent
      trials incorporated similar factorial designs to allow for comparisons between
      steroids, antivirals, both combined, and placebo, and assessed recovery using
      validated measures of facial nerve function. In the larger, blinded trial, the
      numbers needed to treat to achieve complete recovery for patients in the
      prednisolone and acyclovir groups at 9 months were 7.8 (95% confidence interval
      [CI] 5.9-13.7) and 18.7 (95% CI 9.5-infinity), respectively. The number needed to
      treat to achieve complete recovery for patients in the valacyclovir plus
      prednisolone group vs. the prednisolone alone group in the second trial was 14.8
      (95% CI 9.1-744.8). CONCLUSIONS: Current evidence suggests that prednisolone, an
      inexpensive and readily available medication, is effective for this common
      condition, but there was no statistically significant difference observed with
      acyclovir. Valacyclovir provides minimal added benefit to prednisolone alone.

PMID- 19846268
TI  - Neonatal scalp abscess: is it a benign disease?
AB  - BACKGROUND: Neonatal scalp abscesses are a rare but potentially very serious
      condition. OBJECTIVES: This report serves to demonstrate meningitis as a
      potential complication of neonatal scalp abscess. In addition, we review the
      current literature on the subject and comment on the most appropriate evaluation
      and treatment. CASE REPORT: We describe six cases of neonatal scalp abscesses
      with one complication of enterococcal meningitis. CONCLUSION: The emergency
      practitioner should recognize that a neonate with a scalp abscess needs to be
      evaluated for potential serious complications and treated empirically to cover
      for organisms of vaginal origin.

PMID- 19846269
TI  - Steroids for migraine headaches: a randomized double-blind, two-armed, placebo
      controlled trial.
AB  - BACKGROUND: Recurrence of migraine headache after treatment in the emergency
      department (ED) is common. Conflicting evidence exists regarding the utility of
      steroids in preventing migraine headache recurrence at 24-48 h. OBJECTIVE: To
      determine if steroids decrease the headache recurrence in patients treated for
      migraine headaches in the ED. METHODS: Double-blind placebo-controlled, two
      tailed randomized trial. Patients aged >17 years with a moderately severe
      migraine headache diagnosed by treating Emergency Physician were approached for
      participation. Enrollees received either dexamethasone (10 mg i.v.) if
      intravenous access was utilized or prednisone (40 mg by mouth * 2 days) if no
      intravenous access was obtained. Each medication was matched with an identical
      appearing placebo. Patients were contacted 24-72 h after the ED visit to assess
      headache recurrence. RESULTS: A total of 181 patients were enrolled. Eight were
      lost to follow-up, 6 in the dexamethasone group and 2 in the prednisone arm.
      Participants had a mean age of 37 years (+/-10 years), with 86% female. Eighty
      six percent met the International Headache Society Criteria for migraine
      headache. Of the 173 patients with completed follow-up, 20/91 (22%) (95%
      confidence interval [CI] 13.5-30.5) in the steroid arm and 26/82 (32%) (95% CI
      21.9-42.1) in the placebo arm had recurrent headaches (p = 0.21). CONCLUSION: We
      did not find a statistically significant decrease in headache recurrence in
      patients treated with steroids for migraine headaches.

PMID- 19846271
TI  - Internal mammary node metastasis in breast cancer: predictive models to determine
      status & management algorithms.
AB  - AIM: Internal mammary node (IMN) metastases are an important prognostic factor in
      breast cancer. However due to difficulty of access, most surgeons ignore these
      nodes, hence adjuvant treatment decisions may be compromised. Through
      mathematical modeling based on large datasets this study aims to estimate the
      current rate of IMN and sentinel node metastasis. METHODS: Models were created to
      estimate the current rate of axillary and IM sentinel node metastasis. Data from
      historical extended radical mastectomy series were analyzed to project
      contemporary rates of IMN metastasis. This information was coupled with derived
      models and contemporary datasets: a single-institution breast lymphoscintigraphy
      database (1992-2007) to establish lymphatic anatomy; and the Surveillance,
      Epidemiology and End-Results (SEER) registries in the US (2000-2003). RESULTS:
      Rates of IMN metastasis and positive sentinel nodes were estimated and models
      derived to assist with predicting IMN status in patients. If high definition
      peritumoral lymphatic mapping were available, the predicted rates of positive
      sentinel nodes in the axilla (AN) and internal mammary chain (IMN) would be
      equal. We predicted the overall rate of IMN metastasis is approximately 39% the
      rate of positive sentinel AN. CONCLUSION: Simplified models and algorithms can
      predict IMN status.

PMID- 19846270
TI  - Patient-provider communication and perspectives on smoking cessation and relapse
      in the oncology setting.
AB  - OBJECTIVE: To fill a gap in research by examining cancer patient-provider
      communication regarding tobacco use and patients' perspectives regarding their
      experiences with smoking cessation and relapse. METHODS: In-depth interviews were
      conducted with 20 lung and head and neck cancer patients and 11 health care
      providers. RESULTS: Qualitative analyses revealed that cancer patients express
      high levels of motivation to quit smoking; however, patients do not ask providers
      for assistance with quitting and maintaining abstinence and relapsed patients are
      reluctant to disclose smoking behavior due to stigma and guilt. Health care
      providers vary in the advice and type of assistance they supply, and their
      awareness and sensitivity to relapsed patients' feelings. Whereas providers
      emphasized long-term risks of continued smoking in their interactions with
      patients and recommendations for intervention content, patients expressed a
      preference for a balance between risks and benefits. CONCLUSION: Findings
      underscore the need for increased awareness, emphasis, and communication about
      the immediate risks of continued smoking and the benefits of continued abstinence
      specifically for cancer patients. PRACTICE IMPLICATIONS: Our findings demonstrate
      the potential to affect cancer outcomes by improved training in conducting
      smoking cessation and relapse-prevention interventions. Additional training could
      be given to health care providers to increase adherence to clinical practice
      guidelines (5 A's), to learn ways to enhance patients' motivation to maintain
      abstinence, and to deliver smoking messages in a non-threatening manner.

PMID- 19846272
TI  - Transient glycosuria during a urinary tract infection.

PMID- 19846273
TI  - Beta-adrenergic blockade and voice: a double-blind, placebo-controlled trial.
AB  - This study investigated the effects of laboratory-induced stress and beta
      adrenergic blockade on acoustic and aerodynamic voice measures. In a double
      blind, placebo-controlled trial, 12 participants, six males and six females,
      underwent cold pressor-induced sympathetic activation followed by placebo or
      treatment with 40 mg propranolol. Aerodynamic and acoustic parameters of voice
      were collected at baseline, during cold pressor and after treatment with
      propranolol or placebo. Fundamental frequency, jitter, shimmer, maximum airflow
      declination rate, voice onset time, speaking rate, and subglottal pressure were
      measured at baseline, during cold pressor-induced stress, and after treatment
      with propranolol or placebo. Cardiovascular measures served as indicators of
      sympathetic nervous system (SNS) activation by cold pressor and antagonism by
      propranolol, and were collected during all conditions. Cold pressor appeared to
      adequately agonize the SNS as indicated by significant increases in resting
      systolic and diastolic blood pressure and heart rate. Propranolol appeared to
      adequately antagonize the SNS for the participants. Jitter ratio demonstrated a
      statistically significant increase in the participants treated with propranolol.
      Speaking rate demonstrated a small but significant increase in the placebo
      control group during cold pressor. Gender differences were observed in a few
      measures. Cold pressor adequately agonized and propranolol adequately antagonized
      the SNS. No statistically significant differences across subjects were observed
      in the voice parameters during cold pressor-induced stress before treatment.
      Jitter ratio increased significantly during propranolol treatment and cold
      pressor. Speaking rate demonstrated a statistically significant increase during
      cold pressor in the placebo control group. Gender differences were observed, but
      were few.

PMID- 19846274
TI  - Level set fiber bundle segmentation using spherical harmonic coefficients.
AB  - Classifying brain white matter fibers into bundles is of growing interest in
      neuroscience. Quantification of diffusion characteristics inside a fiber bundle
      provides new insights for disease evolutions, therapy effects, and surgical
      interventions. In this paper, we present a novel method for segmenting fiber
      bundles using spherical harmonic coefficients (SHC) that describe diffusion
      signal obtained from High Angular Resolution Diffusion Imaging (HARDI) protocols.
      Based on SHC, we define a similarity measure and use it as a speed function term
      in level set framework. We show advantages of the proposed measure over
      similarity measures based on Diffusion Tensor Imaging (DTI) indices. Without any
      assumptions about diffusion model, we deal with diffusion signal instead of
      orientation distribution function (ODF) calculated using complicated mathematics,
      inaccurate simplifications, and time-consuming implementation. By applying the
      proposed algorithm on synthetic data, its superior accuracy and robustness in low
      SNR conditions are shown. Application of the proposed method on real HARDI MRI
      data also illustrates its superior performance, especially in heterogeneous
      diffusion areas with low traditional diffusion anisotropies.

PMID- 19846275
TI  - Autoimmunity in retinal degeneration: autoimmune retinopathy and age-related
      macular degeneration.
AB  - Autoantibody production is associated with a variety of ocular disorders,
      including autoimmune retinopathy (AIR) and age-related macular degeneration
      (AMD). A breakdown of immunologic tolerance (ocular immune privilege), including
      the blood-retinal barrier, anti-immune and anti-inflammatory proteins, and
      anterior chamber-associated immune deviation may play important roles in these
      disorders. Although the exact triggers for ocular autoimmunity are unknown,
      autoimmune targeting of retinal tissue is clearly associated with and may
      contribute to the pathogenesis of both AIR and AMD. Autoantibody production has
      long been associated with AIR, a collection of disorders that includes cancer
      associated retinopathy, melanoma-associated retinopathy and non-paraneoplastic
      autoimmune retinopathy. A growing body of evidence indicates that AMD
      pathogenesis, too, involves ocular inflammation and autoimmunity. Identification
      and quantification of autoantibodies produced in patients with AIR and AMD may
      assist with diagnosis, prognosis, and choice of treatments. Animal models that
      allow investigation of ocular autoimmunity will also be needed to better
      understand the disease processes and to develop novel therapies. In this review
      we discuss ocular immune privilege and potential mechanisms of autoimmunity in
      the eye. We describe how autoimmunity relates to the pathogenesis of AIR and AMD.
      We explain how the antigen microarray technique is used to detect autoantibodies
      in patient serum samples, and discuss how current animal models for AMD can be
      used to investigate autoimmune pathogenesis. Finally, we outline unanswered
      questions and exciting areas of future study related to autoimmune retinal
      degeneration.

PMID- 19846276
TI  - Emerging roles of TLR7 and TLR9 in murine SLE.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by B
      cell hyperactivity leading to the production of various autoantibodies and
      subsequent development of glomerulonephritis, i.e. lupus nephritis. Among the
      principal targets of autoantibodies produced in murine SLE are nucleic acid
      protein complexes, such as chromatin and ribonucleoproteins, and the envelope
      glycoprotein gp70 of endogenous retroviruses. The preferential production of
      these autoantibodies is apparently promoted by the presence of genetic
      abnormalities leading to defects in the elimination of apoptotic cells and to an
      enhanced expression of endogenous retroviruses. Moreover, recent studies revealed
      that the innate receptors TLR7 and TLR9 are critically involved in the activation
      of dendritic cells and autoreactive B cells through the recognition of endogenous
      DNA- or RNA-containing antigens and subsequent development of autoimmune
      responses against nuclear autoantigens. Furthermore, the regulation of autoimmune
      responses against endogenous retroviral gp70 by TLR7 suggested the implication of
      endogenous retroviruses in this autoimmune response. Clearly, further elucidation
      of the precise molecular role of TLR7 and TLR9 in the development of autoimmune
      responses will help to develop novel therapeutic strategies and targets for SLE.

PMID- 19846277
TI  - Serum inflammatory cytokines, complement components, and soluble interleukin 2
      receptor in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease
      characterized by selective destruction of the intrahepatic bile ducts and highly
      specific serum anti-mitochondrial autoantibodies (AMA). Several studies have
      attempted to determine the cytokine pattern characterizing PBC, yet no definitive
      data have been gathered. The present study was designed to evaluate pro
      inflammatory cytokines (IL-1beta, IL-6, TNFalpha), soluble IL-2 receptor (sIL-2R,
      e.g. soluble CD25), and complement components (C1q, C3, factor B, properdin)
      levels in sera from 84 patients with PBC and 41 controls. PBC was characterized
      by significantly higher levels of all pro-inflammatory cytokines when compared to
      controls; these included IL-1beta (433.3 +/- 13.2 vs. 316.6 +/- 14.7 pg/ml, P <
      0.001), IL-6 (701 +/- 17.4 vs. 158 +/- 22.5 pg/ml, P < 0.001), TNFalpha (3.38 +/-
      0.6 pg/ml vs. undetectable, P = 0.001), and sIL-2R (1527.1 +/- 106 vs. 566.4 +/-
      28.7 U/ml, P < 0.001). Similarly, all complement components were also
      significantly higher in PBC compared to control sera. In conclusion, PBC sera
      manifest higher levels of sIL-2R and complement components and this may reflect a
      perpetuated immune activation. As expected, we also report that all major pro
      inflammatory cytokine levels are enhanced in PBC. Further longitudinal analyses
      could demonstrate a correlation between these markers and disease stage or
      inflammatory activity, to predict histological staging, disease activity, and
      response to treatment.

PMID- 19846278
TI  - Biochemical risk factors for development of obesity in first-episode
      schizophrenia.
AB  - Obesity is a serious health issue for many patients with schizophrenia. There is
      a lack of predictors for and understanding of the development of obesity in the
      early phase of the illness. Therefore we investigated a set of routine
      biochemistry variables in blood as predictors of the development of obesity and
      weight gain over 5 years in an observational cohort study of patients with first
      episode schizophrenia (n=59). Twelve percent of the patients were obese at
      baseline and 37% were obese at the 5-year follow-up. The mean body mass index
      (BMI) change over 5 years was a 4.1 kg/m(2) increase (4.5 SD). Obesity was
      predicted by baseline hemoglobin levels (odds ratio per standard deviation
      [OR/SD] 3.3, 95% confidence interval [CI] 1.4 to 7.5), red blood cell count
      (OR/SD 2.6, 95% CI 1.2 to 5.5), hematocrit (OR/SD 2.8, 95% CI 1.3 to 5.9), gamma
      glutamyltransferase (OR/SD 2.8, 95% CI 1.2-6.3) and creatinine (OR/SD 3.1, 95% CI
      1.2 to 8.0). After adjustment for baseline BMI, the associations were attenuated
      for gamma-glutamyltransferase and creatinine. Low baseline BMI was associated
      with a greater BMI increase. The major conclusion is that easily available
      routine biochemistry markers can be useful in predicting the development of
      obesity in first-episode schizophrenia. The mechanisms underlying the observed
      associations are unknown, but the predictors identified in this study could
      signify dehydration or insulin resistance. These observations open a new window
      to future research on the mechanisms underlying the development of obesity in
      schizophrenia.

PMID- 19846279
TI  - Acetyl-coenzyme A carboxylase alpha gene variations may be associated with the
      direct effects of some antipsychotics on triglyceride levels.
AB  - Acetyl-coenzyme A carboxylase alpha (ACACA) single-nucleotide polymorphism (SNP)
      (rs2229416) was significantly associated with hypertriglyceridemia, during
      exploration of antipsychotic direct effects on lipids. Neuropeptide Y (NPY) gene
      (rs1468271) and ACACB gene (rs2241220) SNPs were significantly associated with
      severe hypercholesterolemia. In the same sample (173 patients on olanzapine,
      quetiapine, chlorpromazine or mirtazapine [increasing the risk of hyperlipidemia]
      and 184 controls taking other antipsychotics), three (rs1266175, rs12453407 and
      rs9906543) of eight additional ACACA SNPs were significantly associated with
      hypertriglyceridemia in those taking drugs of interest, but not in controls. Five
      other ACACA SNPs, three additional NPY SNPs, and seven additional ACACB SNPs were
      not significant.

PMID- 19846280
TI  - The relationship between prepulse inhibition and general psychopathology in
      patients with schizophrenia treated with long-acting risperidone.
AB  - Patients with schizophrenia exhibit impairments in prepulse inhibition (PPI) of
      the startle response. Available data suggest that atypical antipsychotics may be
      more effective than typical antipsychotics in improving PPI deficits in
      schizophrenia. However, previous studies have used between-subjects rather than
      longitudinal within-subjects designs to demonstrate superiority of particular
      atypical antipsychotics over typical antipsychotics in improving PPI in patients
      with schizophrenia. This longitudinal within-subjects test-retest study was
      designed to evaluate changes in PPI and clinical symptoms in patients with
      schizophrenia after switching from the conventional antipsychotic zuclopenthixol
      to long-acting injectable risperidone. PPI was measured in 45 chronic male
      patients with schizophrenia treated with zuclophentixol depot (session T1), and
      12 weeks after switching to long-acting injectable risperidone (session T2).
      Thirty-six healthy control subjects were also evaluated. Patients with
      schizophrenia showed a significant improvement in PPI after changing to long
      acting risperidone. Improvement of PPI deficits between T1 and T2 assessments
      correlated significantly with improvements in PANSS general psychopathology
      subscale scores. Our findings indicate that long-acting risperidone improves PPI
      deficits in subjects with chronic schizophrenia. These results also suggest that
      the PPI-restoring effect of risperidone may be related to improvement in symptoms
      other than positive and negative symptoms.

PMID- 19846281
TI  - The effects of lorazepam on extrastriatal dopamine D(2/3)-receptors-A double
      blind randomized placebo-controlled PET study.
AB  - Lorazepam is a widely used anxiolytic drug of the benzodiazepine class. The
      clinical actions of benzodiazepines are thought to be mediated via specific
      allosteric benzodiazepine binding sites and enhancement of GABAergic
      neurotransmission in the brain. However, the indirect effects of benzodiazepines
      on other neurotransmitter systems have not been extensively studied. Previous
      experimental evidence suggests that benzodiazepines inhibit striatal dopamine
      release by enhancing the GABAergic inhibitory effect on dopamine neurons whereas
      very little is known about cortical or thalamic gamma-amino-butyric (GABA)
      dopamine interactions during benzodiazepine administration. We explored the
      effects of lorazepam (a single 2.5 mg dose) on cortical and thalamic D(2/3)
      receptor binding using Positron-Emission Tomography (PET) and the high-affinity
      D(2/3)-receptor ligand [(11)C]FLB 457 in 12 healthy male volunteers. We used a
      randomized, double-blind and placebo-controlled study design. Dopamine D(2)/D(3)
      receptor binding potential was measured with the reference tissue method in
      several extrastriatal D(2)-receptor areas including frontal, parietal, temporal
      cortices and thalamus. The main subjective effect of lorazepam was sedation.
      Lorazepam induced a statistically significant decrease of D(2)/D(3) receptor
      BP(ND) in medial temporal and dorsolateral prefrontal cortex (DLPFC) that was
      also confirmed by a voxel-level analysis. The sedative effect of lorazepam was
      associated with a decrease in D(2)/D(3) receptor BP(ND) in the DLPFC. In
      conclusion, lorazepam decreased [(11)C]FLB 457 binding in frontal and temporal
      cortex, suggesting that cortical GABA-dopamine interaction may be involved in the
      central actions of lorazepam in healthy volunteers. The correlation between
      lorazepam-induced sedation and D(2)/D(3) receptor binding potential (BP) change
      further supports this hypothesis.

PMID- 19846282
TI  - Fabrication of nanomicelle with enhanced solubility and stability of camptothecin
      based on alpha,beta-poly[(N-carboxybutyl)-L-aspartamide]-camptothecin conjugate.
AB  - This research is aimed to develop a nanomicelle delivery system in order to
      enhance the solubility and stability of camptothecin (CPT) in aqueous media. In
      this case, alpha,beta-poly[(N-carboxybutyl)-L-aspartamide] (PBAsp)-CPT was
      conjugated by the esterification between PBAsp and 20-OH of CPT, and hence used
      to fabricate nanomicelles with a particle size between the pore size of blood
      capillary in normal tissue and that in tumor tissue. It was worthy of note that
      the drug-loaded system of PBAsp-CPT nanomicelle improved the solubility and
      stability of CPT in aqueous media. However, with an increase of the CPT loading
      in PBAsp-CPT, the solubility sharply decreased. Meanwhile, the sizes of PBAsp-CPT
      nanomicelles showed a tendency of increase. Moreover, the drug release of PBAsp
      CPT nanomicelles displayed a linear sustaining profile, and hence resulted in the
      essential decrease of cytotoxicity to L929 cell line. The assembled nanomicelles
      based on the PBAsp-CPT conjugates showed a great potential as polymer prodrug of
      tumor therapy, and the controlled nano-scale might achieve the passive tumor
      targeting.

PMID- 19846283
TI  - Tat peptide mediated cellular uptake of SiO2 submicron particles.
AB  - Internalization of nano- and microparticles into live cells correlates closely
      with their potential applications, functions, cytotoxicity and intracellular drug
      delivery. Particularly, delivery of a large variety of cargoes such as proteins,
      peptides, nucleic acids and small particles into cells could be enhanced by some
      ligands such as Tat peptide. In this work, the ability of Tat mediated cellular
      uptake was assessed. The Tat peptide was covalently immobilized to fluorescein
      tagged SiO2 particles (FITC-SiO2-NH2 particles) with a diameter of 200 nm. BCA
      protein assay determined that the grafting amount of the Tat peptide could be
      controlled within a range of 0-3.5 microg/mg SiO2 particles by the Tat feeding
      amount. Surface immobilization of the Tat peptide did not bring apparent changes
      on the surface morphology and charge property of the SiO2-NH2 particles. By
      contrast, the surface charge of both the FITC-SiO2-NH2 particles and the FITC
      SiO2-Tat particles was reversed from slight positive in Dulbecco's Modified
      Eagles Medium (DMEM) to slight negative in DMEM/fetal bovine serum, conveying
      adsorption of plasma proteins on the particles. Flow cytometry measurement showed
      that the FITC-SiO2-Tat particles were internalized by HepG2 cells with a
      significant faster rate and a higher number of particles than that of the FITC
      SiO2-NH2 particles. Moreover, internalization of the Tat peptide decorated
      particles was less influenced by the low temperature at 4 degrees C. The Tat
      decoration affected the subcellular distribution of the particles as well,
      resulting in localization of the particles in the cell nucleus. No obvious
      cytotoxicity was detected for both the FITC-SiO2-NH2 particles and the FITC-SiO2
      Tat particles.

PMID- 19846284
TI  - Candida rugosa lipase Lip1-polyethyleneglycol interaction and the relation with
      its partition in aqueous two-phase systems.
AB  - The interaction between a lipase from Candida rugosa (Lip1) and
      polyethyleneglycols of different molecular masses was studied using fluorescence
      and circular dichroism approaches in order to be applied to the analysis of the
      enzyme partition mechanism in aqueous two-phase systems of polyethyleneglycol
      potassium phosphate. The decrease of the partition coefficients with the
      polyethyleneglycol molecular mass showed that the enzyme partition is driven by
      the excluded volume effect and not by the enzyme-polymer interaction. The polymer
      did not affect the secondary and tertiary structure of the enzyme nor its
      biological activity. The lipase from Candida rugosa lyophilizate was partitioned
      in favour of the polyethyleneglycol rich phase; PEG 2000 being the system which
      showed the better enzyme recovery (78.26%) with a purification factor of 2.3.
      This method could be applied as a first step to isolate the enzyme from a culture
      medium with good recovery and without modifying the enzymatic capacity and the
      molecular structure.

PMID- 19846285
TI  - Surface plasmon resonance biosensor based on Au nanoparticle in titania sol-gel
      membrane.
AB  - A novel surface plasmon resonance (SPR) biosensor for the determination of human
      IgG was introduced. The biosensor was prepared with three layers of titania sol
      gel membrane by vapor deposition. The colloid Au nanoparticle (AuNP) was
      immobilized in the second layer of titania membrane and the AuNP coupled with
      rabbit anti-human IgG was encapsulated in the third layer. The AuNP in the second
      layer of titania membrane was proved to be effective in the sensitivity
      enhancement of SPR biosensor. The lowest concentration that could be detected
      obtained by the biosensor with AuNP is about eight times lower than that obtained
      without AuNP. In addition, the titania sol-gel is a porous homogeneous material
      that permits analytes to access the encapsulated biomolecule and can provide a
      controlled environment for the study of biomolecular recognition. The titania sol
      gel was also confirmed to be benefit for biomolecule to keep bioactivity, which
      could offer a good waterish microenvironment. As a result, the modified biosensor
      exhibits a satisfactory response for human IgG in the concentration range of 0.30
      40.00 microg mL(-1) and shows favorable bioactivity for a long time.

PMID- 19846286
TI  - Effect of omalizumab on peripheral blood eosinophilia in allergic asthma.
AB  - Eosinophilia is an established marker of asthma-related inflammation. We assessed
      the effect of omalizumab on peripheral blood eosinophil counts using a pooled
      analysis of data from five randomized, double-blind, placebo-controlled studies
      in patients with moderate-to-severe persistent allergic asthma receiving moderate
      to-high-dose inhaled corticosteroids (omalizumab, n=1136; placebo, n=1100).
      Relationships between omalizumab, peripheral blood eosinophils, serum free IgE
      concentrations and clinical outcomes were explored. Baseline mean eosinophil
      counts were similar in each treatment group. Post-treatment eosinophil counts
      were significantly reduced from baseline in the omalizumab group (p<0.0001) but
      were not significantly different in the placebo group. Greater reductions in
      eosinophil counts were observed in patients who had post-treatment free IgE
      levels <50ng/mL. Three studies included steroid-stable and steroid-reduction
      phases. At the end of each phase in these studies, a significantly greater
      reduction in eosinophil counts was achieved in the omalizumab group compared with
      the placebo group (p<0.0001). A consistent pattern of improved clinical
      outcomes/decreased eosinophils and worsened clinical outcomes/increased
      eosinophils was observed for both omalizumab and placebo treatment groups. The
      findings from our analysis of a large patient population are consistent with
      earlier reports of the inhibitory effect of omalizumab on eosinophils.

PMID- 19846287
TI  - Sister chromatid tension and the spindle assembly checkpoint.
AB  - The spindle assembly checkpoint (SAC) is a feedback control system that monitors
      the state of kinetochore/microtubule attachment during mitosis and halts cell
      cycle progression until all chromosomes are properly aligned at the metaphase
      plate. The state of chromosome-microtubule attachment is implicated as a crucial
      factor in the checkpoint response. On the contrary, lack of tension in the
      centromere-kinetochore region of sister chromatids has been shown to regulate a
      pathway of correction of undesired chromosome-microtubule connections, while the
      presence of tension is believed to promote the stabilization of attachments. We
      discuss how tension-sensitive phenomena, such as attachment correction and
      stabilization, relate to the SAC and we speculate on the existence of a single
      pathway linking error correction and SAC activation.

PMID- 19846288
TI  - Herding Hippos: regulating growth in flies and man.
AB  - Control of cell number requires the coordinate regulation of cell proliferation
      and cell death. Studies in both the fly and mouse have identified the Hippo
      kinase pathway as a key signaling pathway that controls cell proliferation and
      apoptosis. Several studies have implicated the Hippo pathway in a variety of
      cancers. Recent studies have also revealed a role for the Hippo pathway in the
      control of cell fate decisions during development. In this review, we will cover
      the current model of Hippo signaling in development. We will explore the
      differences between the Hippo pathway in invertebrates and mammals, and focus on
      recent advances in understanding how this conserved pathway is regulated.

PMID- 19846291
TI  - MicroRNAs in brain development and physiology.
AB  - The crucial role of microRNAs (miRNAs) in brain development is demonstrated by
      the dramatic apoptotic phenotypes of mouse mutants abolishing all miRNAs
      synthesis. Recent advances in Caenorhabditis elegans, Drosophila, zebrafish and
      mouse moved beyond this global understanding by targeting selected miRNAs. They
      indicate that single miRNAs successively modulate all steps of brain maturation,
      including patterning, neurogenesis, neuronal differentiation and subtype
      specification, and neuronal activity. In detail, they reveal an amazing
      functional complexity: specific miRNAs can either be used reiteratively, such as
      miR-9 in patterning, neurogenesis and differentiation, or concomitantly target
      different mRNAs in distinct cellular compartments, such as Pumilio or Limk1 that
      can be inhibited by miR-134 to control neuritogenesis or spine growth,
      respectively. Their regulation can be composite, either through multiple loci
      (miR-9) or in blocks of numerous miRNAs (miR-134). A major step remains to
      decipher their impact on brain function, in particular in the control of
      behaviour.

PMID- 19846290
TI  - Nuclear organization in the 3D space of the nucleus - cause or consequence?
AB  - Recent evidence suggests that dynamic three-dimensional genomic interactions in
      the nucleus exert critical roles in regulated gene expression. Here, we review a
      series of recent paradigm-shifting experiments that highlight the existence of
      specific gene networks within the self-organizing space of the nucleus. These
      gene networks, evidenced by long-range intrachromosomal and interchromosomal
      interactions, can be considered as the cause or consequence of regulatory
      biological programs. Changes in nuclear architecture are a hallmark of
      laminopathies and likely potentiate genome rearrangements critical for tumor
      progression, in addition to potential vital contribution of noncoding RNAs and
      DNA repeats. It is virtually certain that we will witness an ever-increasing rate
      of discoveries that uncover new roles of nuclear architecture in transcription,
      DNA damage/repair, aging, and disease.

PMID- 19846292
TI  - Effects of nutrients, pH and water potential on exopolysaccharides production by
      a fungal strain belonging to Ganoderma lucidum complex.
AB  - Exopolysaccharide (EPS) production by Ganoderma lucidum in response to different
      culture conditions was studied. Cellulose and glucose, in defined media, resulted
      in the more efficient enhancers of EPS production among the carbon sources
      tested. In natural media cultures containing glucose and malt extract exhibited a
      marked increase (up to 29-fold) respect to defined media. Subsequently, high malt
      extract and glucose concentrations were tested. G. lucidum produced two fractions
      of EPS, water-soluble and water-insoluble under these culture conditions. The
      maximum value (15 g L(-1)) was reached at 21 days in the medium containing 60 g
      L(-1) malt extract and 40 g L(-1) glucose. The incomplete utilization of reducing
      sugars by the fungus in these media suggested that not only did high malt extract
      and glucose concentrations play a role in EPS production but also the water
      activity might be involved. A factorial uniform experimental design to test the
      effect of malt extract, polyethylene glycol (PEG, as water activity depressor),
      and initial pH on specific EPS production was applied. G. lucidum showed to be a
      more efficient specific EPS (mg EPS per g mycelium) producer at pH 3.5 in
      cultures containing the highest PEG and malt extract concentrations.

PMID- 19846289
TI  - Role of secondary lymphoid tissues in primary and memory T-cell responses to a
      transplanted organ.
AB  - Secondary lymphoid tissues are the hub of adaptive immune responses wherein rare
      cognate lymphocytes encounter dendritic cells bearing antigen from peripheral
      tissues and differentiate into effector and memory cells that eliminate antigen.
      It is accepted that immune responses against microbial and tumor antigens are
      initiated within secondary lymphoid tissues. There is less agreement on whether
      the same principle applies to immune responses to a transplanted organ because an
      allograft expresses foreign major histocompatibility complex and contains donor
      antigen presenting cells that could activate T cells directly in situ leading to
      rejection. Recent studies confirm that although naive T cells can be primed
      within the allograft, their differentiation to effect rejection is dependent on
      secondary lymphoid tissues. Antigen-experienced memory T cells, unlike Naive T
      cells, function largely independent of secondary lymphoid tissues to cause
      allograft rejection. In an alloimmune response, secondary lymphoid tissues
      support not only immune activation but also immune regulation essential for
      allograft survival. Here, we will review recent findings and discuss the role of
      secondary lymphoid tissues in primary and memory alloimmune responses.

PMID- 19846293
TI  - Influence of apple cultivar and juice pasteurization on hard cider and eau-de-vie
      methanol content.
AB  - Apple eau-de-vie is a traditional alcoholic beverage produced in France by
      distillation of fermented apple juice (hard cider). The current research was
      undertaken to determine the methanol content of hard cider and apple eau-de-vie
      made from four apple cultivars grown in the Finger Lakes region of New York
      State. The methanol concentration of hard cider varied from 0.037% to
      approximately 0.091%, and the methanol content of apple eau-de-vie ranged from
      below 200 mg to more than 400 mg/100mL of 40% ethanol. The United States legal
      limit of methanol for fruit brandy is 0.35% by volume or 280 mg/100mL of 40%
      ethanol. Of the four apple cultivars examined, Crispin apples yielded
      significantly more methanol in hard cider and eau-de-vie than Empire, Jonagold or
      Pacific Rose apples. Pasteurization of Crispin apple juice prior to alcoholic
      fermentation significantly reduced the methanol content of hard cider and eau-de
      vie.

PMID- 19846294
TI  - Scale-up of diluted sulfuric acid hydrolysis for producing sugarcane bagasse
      hemicellulosic hydrolysate (SBHH).
AB  - Sugarcane bagasse was pretreated with diluted sulfuric acid to obtain sugarcane
      bagasse hemicellulosic hydrolysate (SBHH). Experiments were conducted in
      laboratory and semi-pilot reactors to optimize the xylose recovery and to reduce
      the generation of sugar degradation products, as furfural and 5
      hydroxymethylfurfural (HMF). The hydrolysis scale-up procedure was based on the H
      Factor, that combines temperature and residence time and employs the Arrhenius
      equation to model the sulfuric acid concentration (100 mg(acid)/g(dm)) and
      activation energy (109 kJ/mol). This procedure allowed the mathematical
      estimation of the results through simulation of the conditions prevailing in the
      reactors with different designs. The SBHH obtained from different reactors but
      under the same H-Factor of 5.45+/-0.15 reached similar xylose yield
      (approximately 74%) and low concentration of sugar degradation products, as
      furfural (0.082 g/L) and HMF (0.0071 g/L). Also, the highest lignin degradation
      products (phenolic compounds) were rho-coumarilic acid (0.15 g/L) followed by
      ferulic acid (0.12 g/L) and gallic acid (0.035 g/L). The highest concentration of
      ions referred to S (3433.6 mg/L), Fe (554.4 mg/L), K (103.9 mg/L). The H-Factor
      could be used without dramatically altering the xylose and HMF/furfural levels.
      Therefore, we could assume that H-Factor was directly useful in the scale-up of
      the hemicellulosic hydrolysate production.

PMID- 19846295
TI  - Protein tyrosine phosphatase 1B inhibitors isolated from Morus bombycis.
AB  - Bioassay-guided fractionation of the chloroform-soluble fraction of Morus
      bombycis, using an in vitro PTP1B inhibitory assay led to the identification of
      three 2-arylbenzofurans, albafuran A (1), mulberrofuran W (2) and mulberrofuran D
      (6), along with three chalcone-derived Diels-Alder products, kuwanon J (3),
      kuwanon R (4), and kuwanon V (5). Compounds 1-6 showed remarkable inhibitory
      activity against PTP1B with IC(50) values ranging from 2.7 to 13.8 microM.
      Inhibition kinetics were analyzed by Lineweaver-Burk plots, which suggested that
      compounds 1-6 inhibited PTP1B in a mixed-type manner. The present results
      indicate that the respective lipophilic and hydroxyl groups of 2-arylbenzofurans
      and chalcone-derived Diels-Alder products play an important role in inhibition of
      PTP1B.

PMID- 19846296
TI  - Factors affecting anti-inflammatory effect of chitooligosaccharides in
      lipopolysaccharides-induced RAW264.7 macrophage cells.
AB  - In this study, factors affecting anti-inflammatory effect of
      chitooligosaccharides (COSs) in lipopolysaccharides (LPS)-induced RAW264.7
      macrophage cells were investigated. The inhibition of NO secretion by COSs
      revealed that 90-COSs (90% N-deacetylation) significantly inhibited NO secretion
      than those of 50-COSs (50% N-deacetylation), and 90-HMWCOS (5000-10,000Da) in the
      90-COSs showed the highest inhibition activity. Furthermore, 90-HMWCOSs also
      found to inhibit LPS-stimulated production of PGE(2), TNF-alpha and IL-6, as well
      as the expression of iNOS, COX-2, TNF-alpha, and IL-6. These results suggested
      that 90-HMWCOS may have anti-inflammatory effect via down-regulation of
      transcriptional and translational expression levels of TNF-alpha, IL-6 and iNOS
      and COX-2.

PMID- 19846297
TI  - A new approach to the synthesis of polyunsaturated deuterated isoprostanes: total
      synthesis of d4-5-epi-8,12-iso-iPF3alpha-VI and d4-8,12-iso-iPF3alpha-VI.
AB  - The total and stereospecific synthesis of d(4)-5-epi-8,12-iso-iPF(3alpha)-VI 55
      and d(4)-8,12-iso-iPF(3alpha)-VI 64, EPA-derived all-syn-isoprostanes (iPs), has
      been accomplished. Because of issues related to volatility and yield with some of
      the primary deuterated synthons an improved synthesis is presented. These two
      deuterated analogs were used to discover and quantify the presence of the
      corresponding endogenous isoprostanes in human urine. These assays may serve as a
      valuable index of oxidative stress in population with omega-3 fatty acid enriched
      diets containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and
      may also be useful as an index of the severity of inflammatory diseases such as
      atherosclerosis and Alzheimer's disease.

PMID- 19846298
TI  - Evaluation of basic, heterocyclic ring systems as templates for use as potassium
      competitive acid blockers (pCABs).
AB  - A variety of basic, heterocyclic templates has been reported as potassium
      competitive, acid pump antagonists. Herein, we report a comparison of potencies
      of these templates and others to establish which offers the best start point for
      further systematic optimisation. Modifications were carried out to improve the
      developability profile of the more potent 1H-pyrrolo[2,3-c]pyridine template,
      affording molecules with improved overall in vitro characteristics versus the
      reported clinical candidate AR-H047108, and comparable to the clinically
      efficacious AZD-0865.

PMID- 19846299
TI  - Histamine H3 and H4 receptor affinity of branched 3-(1H-imidazol-4-yl)propyl N
      alkylcarbamates.
AB  - A series of imidazole-containing (non-)chiral carbamates were tested at human
      histamine H(3) receptor (H(3)R). All compounds displayed K(i) values below 100
      nM. A trend for a stereoselectivity at human H(3)R was observed for the chiral
      alpha-branched ligands. Selected compounds were also tested at human histamine
      H(4) receptor and showed moderate to weak affinities (118-1460 nM).

PMID- 19846300
TI  - Soluble polyphenols: synthesis and bioavailability of 3,4',5-tri(alpha-D-glucose
      3-O-succinyl) resveratrol.
AB  - We report the development of a chemical modification method of general
      applicability to polyphenols, which increases solubility to influence absorption.
      Glucosyl groups were added to the resveratrol kernel via a succinate linker,
      yielding 3,4',5-tri-(alpha-D-glucose-3-O-succinyl) resveratrol. The construct was
      only slowly hydrolyzed in acid and at pH 6.8, but it was destroyed by blood
      esterases in less than 1h. In rats its administration resulted in a blood
      concentration versus time curve shifted to longer times in comparison to
      resveratrol, a useful modulation of pharmacokinetics. The area-under-curve
      parameter and the metabolite mix were similar to those of resveratrol. The method
      may be advantageously employed to solubilize other polyphenols and to make them
      more palatable.

PMID- 19846301
TI  - Carbonic anhydrase inhibitors. Characterization and inhibition studies of the
      most active beta-carbonic anhydrase from Mycobacterium tuberculosis, Rv3588c.
AB  - The Rv3588c gene product of Mycobacterium tuberculosis, a beta-carbonic anhydrase
      (CA, EC 4.2.1.1) denominated here mtCA 2, shows the highest catalytic activity
      for CO(2) hydration (k(cat) of 9.8 x 10(5)s(-1), and k(cat)/K(m) of 9.3 x 10(7)M(
      1)s(-1)) among the three beta-CAs encoded in the genome of this pathogen. A
      series of sulfonamides/sulfamates was assayed for their interaction with mtCA 2,
      and some diazenylbenzenesulfonamides were synthesized from
      sulfanilamide/metanilamide by diazotization followed by coupling with amines or
      phenols. Several low nanomolar mtCA 2 inhibitors have been detected among which
      acetazolamide, ethoxzolamide and some 4-diazenylbenzenesulfonamides (K(I)s of 9
      59 nM). As the Rv3588c gene was shown to be essential to the growth of M.
      tuberculosis, inhibition of this enzyme may be relevant for the design of
      antituberculosis drugs possessing a novel mechanism of action.

PMID- 19846302
TI  - A facile synthesis and biological activity of novel
      tetrahydrobenzo[4',5']thieno[3',2':5,6]pyrido[4,3-d]pyrimidin-4(3H)-ones.
AB  - The synthesis and biological activity of 2-substituted-8,9,10,11
      tetrahydrobenzo[4',5']thieno[3',2':5,6] pyrido[4,3-d]pyrimidin-4(3H)-ones are
      described. Bioassay results indicated that these compounds have antifungal
      activity against Botrytis cinerea at a concentration of 50mg/L. In addition,
      compounds 5m and 5n were effective to both KB cells and their parent multidrug
      resistant KBv200 cells with the overexpression of ABCB1. For example, compound 5m
      showed the best inhibition against KB and KBv200 cells with IC(50) values of 17.4
      and 25.4 microM, respectively.

PMID- 19846303
TI  - Synthesis and biological evaluation of heterocyclic ring-substituted maslinic
      acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B.
AB  - A series of maslinic acid derivatives have been synthesized by introducing
      various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory
      effects on PTP1B, TCPTP and related PTPs are evaluated. Most of the compounds
      exhibited a dramatic increase in inhibitory potency and selectivity, the two most
      potent PTP1B inhibitors 20 (IC(50)=0.61 microM) and 29 (IC(50)=0.64 microM)
      showed about 10-fold more potent than lead compound maslinic acid. More
      importantly, 29 possesses the best selectivity of 6.9-fold for PTP1B over TCPTP.

PMID- 19846304
TI  - A plausible role of salivary copper in antimicrobial activity of histatin-5-
      metal binding and oxidative activity of its copper complex.
AB  - Histatin-5 (Hn5) is an antimicrobial salivary peptide of 24 amino acids. Two
      specific metal-binding sites were revealed with electronic, NMR, and EPR
      spectroscopy. The complex Cu(2)(II)-Hn5 effectively oxidizes catechol, exhibiting
      enzyme-like kinetics (k(cat)=0.011 and 0.060 s(-1) and k(cat)/K(m)=19 and 50 M(
      1)s(-1) without and with 12.8mM H(2)O(2), respectively). The significant
      oxidative activity may contribute to the biological activity of this antibiotic
      metallopeptide.

PMID- 19846306
TI  - The difficulty in confirming clinical diagnosis of myasthenia gravis in a
      seronegative patient: a possible neurophysiological approach.
AB  - In seronegative myasthenia gravis repetitive nerve stimulation and single-fibre
      EMG have a crucial diagnostic value but they may be negative, particularly in
      repetitive nerve stimulation studies. We report the case of a 43-year-old patient
      with generalized seronegative myasthenia gravis with negative 3 Hz repetitive
      nerve stimulation at Erb's point and voluntary single-fibre EMG in the
      orbicularis oculi. We also performed 6 and 12 Hz repetitive nerve stimulation at
      Erb and stimulated single-fibre EMG in the extensor digitorum communis and our
      findings were pathological. Our data suggest that, for individual patients with
      an atypical picture characterised by dissociation between a severe clinical
      pattern and no definite neurophysiological findings on conventional tests,
      repetitive nerve stimulation with a stimulation rate higher than 3 Hz and/or
      stimulated single-fibre EMG with an increasing stimulation rate may be helpful.

PMID- 19846305
TI  - Biaryl purine derivatives as potent antiproliferative agents: inhibitors of
      cyclin dependent kinases. Part I.
AB  - The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino
      group of the Cdk inhibitor roscovitine (2), maintained the potent Cdk inhibition
      demonstrated by roscovitine (2) as well as greatly improving the
      antiproliferative activity. A series of C-6 biarylmethylamino derivatives was
      prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions
      to provide compounds that displayed potent cytotoxic activity against tumor cell
      lines. In particular, derivative 21h demonstrated a >750-fold improvement in the
      growth inhibition of HeLa cells compared to roscovitine (2).

PMID- 19846307
TI  - Patient Registries and Trial Readiness in Myotonic Dystrophy--TREAT-NMD/Marigold
      International Workshop Report.

PMID- 19846308
TI  - Antisense oligonucleotide therapeutics for iron-sulphur cluster deficiency
      myopathy.
AB  - Iron-sulphur cluster deficiency myopathy is caused by a deep intronic mutation in
      ISCU resulting in inclusion of a cryptic exon in the mature mRNA. ISCU encodes
      the iron-sulphur cluster assembly protein IscU. Iron-sulphur clusters are
      essential for most basic redox transformations including the respiratory-chain
      function. Most patients are homozygous for the mutation with a phenotype
      characterized by a non-progressive myopathy with childhood onset of early
      fatigue, dyspnoea and palpitation on trivial exercise. A more severe phenotype
      with early onset of a slowly progressive severe muscle weakness, severe exercise
      intolerance and cardiomyopathy is caused by a missense mutation in compound with
      the intronic mutation. Treatment of cultured fibroblasts derived from three
      homozygous patients with an antisense phosphorodiamidate morpholino
      oligonucleotide for 48 h resulted in 100% restoration of the normal splicing
      pattern. The restoration was stable and after 21 days the correctly spliced mRNA
      still was the dominating RNA species.

PMID- 19846309
TI  - The PedsQL in pediatric patients with Spinal Muscular Atrophy: feasibility,
      reliability, and validity of the Pediatric Quality of Life Inventory Generic Core
      Scales and Neuromuscular Module.
AB  - For Phase II and III clinical trials in children with Spinal Muscular Atrophy
      (SMA), reliable and valid outcome measures are necessary. Since 2000, the
      American Spinal Muscular Atrophy Randomized Trials (AmSMART) group has
      established reliability and validity for measures of strength, lung function, and
      motor function in the population from age 2 years to 18 years. The PedsQL
      (Pediatric Quality of Life Inventory) Measurement Model was designed to integrate
      the relative merits of generic and disease-specific approaches, with disease
      specific modules. The PedsQL 3.0 Neuromuscular Module was designed to measure
      HRQOL dimensions specific to children ages 2-18 years with neuromuscular
      disorders, including SMA. One hundred seventy-six children with SMA and their
      parents completed the PedsQL 4.0 Generic Core Scales and PedsQL 3.0 Neuromuscular
      Module. The PedsQL demonstrated feasibility, reliability, and validity in the SMA
      population. Consistent with the conceptualization of disease-specific symptoms as
      causal indicators of generic HRQOL, the majority of intercorrelations among the
      Neuromuscular Module Scales and the Generic Core Scales were in the medium to
      large range, supporting construct validity. For the purposes of a clinical trial,
      the PedsQL Neuromuscular Module and Generic Core Scales provide an integrated
      measurement model with the advantages of both generic and condition-specific
      instruments.

PMID- 19846310
TI  - Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental
      conundrum.
AB  - While the presence of phosphoinositides in the nuclei of eukaryotes and the
      identity of the enzymes responsible for their metabolism have been known for some
      time, their functions in the nucleus are only now emerging. This is illustrated
      by the recent identification of effectors for nuclear phosphoinositides. Like the
      cytosolic phosphoinositide signaling pathway, nuclear phosphatidylinositol 4,5
      bisphosphate (PI4,5P(2)) is at the center of the pathway and acts both as a
      messenger and as a precursor for many additional messengers. Here, recent
      advances in the understanding of nuclear phosphoinositide signaling and its
      functions are reviewed with an emphasis on PI4,5P(2) and its role in gene
      expression. The compartmentalization of nuclear phosphoinositide phosphates
      (PIP(n)) remains a mystery, but emerging evidence suggests that phosphoinositides
      occupy several functionally distinct compartments.

PMID- 19846311
TI  - Detection of MCP-1 and IL-8 in the serum and cerebrospinal fluid of a child with
      Miller Fisher syndrome.
AB  - We describe an 11-year-old female patient who presented with a 7-day history of
      diplopia and difficulty walking. On examination she had ataxia, areflexia and
      ophthalmoplegia, and a diagnosis of Miller Fisher syndrome (MFS) was made after
      the exclusion of other conditions. Monocyte chemotactic protein-1 (MCP-1) and
      interleukin (IL)-8 chemokine levels in the cerebrospinal fluid (CSF) were
      significantly increased in the acute phase. We believe MFS in this patient was
      due to both peripheral nervous system dysfunction, and central nervous system
      (CNS) involvement. The cause of MFS in this patient was suggested by the
      localized chemokine production in the CSF. The high expression of MCP-1 and IL-8
      chemokines suggest that macrophages and T cells may stimulate inflammation of the
      CNS in MFS.

PMID- 19846313
TI  - Observing biological dynamics at atomic resolution using NMR.
AB  - Biological macromolecules are highly flexible and continually undergo
      conformational fluctuations on a broad spectrum of timescales. It has long been
      recognized that dynamics have an important role in the action of these molecules.
      However, the relationship between molecular function and motion is extremely
      challenging to delineate, because the conformational space available to
      macromolecules is vast and the relevant excursions can be infrequent and short
      lived. Recent advances in solution nuclear magnetic resonance (NMR) spectroscopy
      permit biomolecular dynamics to be observed with unprecedented detail.
      Applications of these new NMR techniques to the study of fundamental processes
      such as binding and catalysis have provided new insights into how living systems
      operate at an atomic level.

PMID- 19846312
TI  - Plasticity of telomere maintenance mechanisms in yeast.
AB  - Telomeres, the nucleoprotein structures located at linear eukaryotic chromosomal
      termini, are essential for chromosome stability and are maintained by the special
      reverse transcriptase named telomerase. In the Saccharomycotina subphylum of
      budding yeast, telomere repeat sequences and binding factors, as well as
      telomerase components, are exceptionally diverse and distinct from those found in
      other eukaryotes. In this survey, I report a comparative analysis of the domain
      structures of telomere and telomerase-related factors made possible by the recent
      sequencing of multiple yeast genomes. This analysis revealed both conserved and
      variable aspects of telomere maintenance. Based on these findings, I propose a
      plausible series of evolutionary events in budding yeast to account for its
      exceptional telomere structural divergence.

PMID- 19846314
TI  - Efficient microwave-assisted direct radiosynthesis of [(18)F]PR04.MZ and
      [(18)F]LBT999: selective dopamine transporter ligands for quantitative molecular
      imaging by means of PET.
AB  - PR04.MZ 8-(4-fluoro-but-2-ynyl)-3-p-tolyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic
      acid methyl ester (1) and LBT999 8-((E)-4-fluoro-but-2-enyl)-3b-p-tolyl-8-aza
      bicyclo[3.2.1]octane-2beta-carboxylic acid methyl ester (2) are selective
      dopamine reuptake inhibitors, derived from cocaine. Compounds 1 and 2 were
      labelled with fluorine-18 at their terminally fluorinated N-substituents
      employing microwave enhanced direct nucleophilic fluorination. K[(18)F]F(-)
      Kryptofix 222 cryptate, tetrabutyl ammonium [(18)F]fluoride and caesium
      [(18)F]fluoride were compared as fluoride sources under conventional and
      microwave enhanced conditions. Fluorination yields were remarkably increased
      under microwave irradiation for all three fluoride salts. Radiochemically pure
      (>98%) [(18)F]PR04.MZ (0.95-1.09GBq, 42-135GBq/micromol) was obtained within 34
      40min starting from 3.0GBq [(18)F]fluoride ion in 32-36% non-decay-corrected
      overall yield using K[(18)F]F(-)Kryptofix 222 cryptate in MeCN.

PMID- 19846315
TI  - Pretransplant pulmonary hypertension and long-term allograft right ventricular
      function.
AB  - BACKGROUND: Graft right ventricular (RV) function is compromised directly
      posttransplant, especially in heart transplantation (HTx) recipients with
      pretransplant pulmonary hypertension (PH). Graft RV size and systolic function,
      and the effect of the recipient's pulmonary haemodynamics on the graft
      extracellular matrix are not well characterised in the patients long-term after
      HTx. AIM: Comparison of RV size and systolic function in HTx recipients' long
      term posttransplant stratified by the presence of pretransplant PH. METHODS: HTx
      survivors >or=2 years posttransplant were divided into group I without
      pretransplant PH (pulmonary vascular resistance, PVR <2.5 Wood units, n=37) and
      group II with PH (PVR >or=2.5 Wood units, n=16). RV size and systolic function
      were measured using cardiac magnetic resonance imaging (CMR). The collagen
      content was assessed in septal endomyocardial biopsies obtained at HTx and at
      study inclusion. RESULTS: Mean posttransplant follow-up was 5.2+/-2.9 years
      (group I) and 4.9+/-2.2 years (group II) (p=0.70). PVR was 1.5+/-0.6 vs 4.1+/-1.7
      Wood units pretransplant (p<0.001), and 1.2+/-0.5 vs 1.3+/-0.5 Wood units at
      study inclusion (p=0.43). Allograft RV size and systolic function were similar in
      both groups (p always >or=0.07). Collagen content at transplantation and at
      follow-up were not different (p always >or=0.60). CONCLUSION: Posttransplant
      normalisation of pretransplant PH is associated with normal graft RV function
      long-term after HTx.

PMID- 19846317
TI  - Migration of an Amplatzer after patent ductus arteriosus closure.

PMID- 19846316
TI  - Sutureless rescue of a severely hypoplastic pulmonary artery.
AB  - The management of severely hypoplastic pulmonary arteries in the adolescent or
      adult with congenital heart disease is challenging. A patient with pulmonary
      atresia and ventricular septal defect (PA-VSD) presented with severe cyanosis due
      to a kinked and thrombosed right ventricle to pulmonary artery conduit.
      Retrograde wedge angiography showed a patent right and a diminutive left
      pulmonary artery deep in the lung hilus. Treatment options were limited and
      therefore a different strategy had to be considered to rescue the lung segments.
      This case report describes the novel use of a covered stent to successfully
      obtain a sutureless connection between a vascular graft and a diminutive
      pulmonary artery during a hybrid procedure.

PMID- 19846318
TI  - Geometric distortion of the mitral annulus by the thrombosed aneurysmal coronary
      sinus with ostium stenosis resulting in mitral regurgitation.

PMID- 19846319
TI  - A vaccine measured with a highly variable assay: rabies.
AB  - Manufacturers and regulators are challenged when evaluating stability of vaccines
      when potency is measured using a highly variable assay. Participants in the IABS
      Workshop on Stability Evaluation of Vaccines, a Life Cycle Approach, were offered
      a case study from a series of stability studies of a rabies vaccine, using the
      NIH potency assay. The case study was introduced with a scenario in which a new
      manufacturer was to formulate, lyophilize and fill the vaccine from bulk supplied
      by another manufacturer. The regulatory authority requested that data from the
      new manufacturer be supplied, to supplement that of the original producer.
      Participants were asked to answer a series of questions posed by the regulator,
      and critique the study design and data analysis according to principles described
      during the workshop.

PMID- 19846320
TI  - The role of tumor vascularity in predicting survival after yttrium-90
      radioembolization for liver metastases.
AB  - PURPOSE: It is unclear what role pretreatment tumor vascularity plays in
      determining outcomes after yttrium-90 radioembolization. A hypothesis was tested
      that radiographic vascularity of a tumor does not affect patient survival.
      MATERIALS AND METHODS: In this two-institution retrospective study, 137 patients
      with metastatic liver disease underwent (90)Y radioembolization. Primary sites
      were categorized as colon, neuroendocrine, and other. All patients underwent
      triphasic contrast-enhanced computed tomography (CT) or magnetic resonance
      imaging, as well as detailed hepatic angiography. Two board-certified
      interventional radiologists interpreted all images and evaluated them for the
      presence of enhancement. Median survival times, as well as 1- and 2-year survival
      rates, were compared between patients with hypervascular and hypovascular tumors
      on (i) cross-sectional imaging and (ii) angiography with use of the log-rank
      statistic (alpha = 0.05). RESULTS: On angiography, 108 patients had hypervascular
      tumors and 29 had hypovascular tumors. Median survival times for the two
      subgroups were 300 days and 261 days, respectively (P = .95). On CT, 24 patients
      had hypervascular tumors and 113 had hypovascular tumors. Median survival times
      for these subgroups were 306 days and 284 days, respectively (P = .67). Eighty
      four patients' tumors that were hypovascular on CT were hypervascular on
      angiography. There were no statistical differences in survival between patients
      with hypervascular and hypovascular tumors, regardless if vascularity was defined
      based on CT or angiography. CONCLUSIONS: Radiographic vascular appearance of
      liver tumors, regardless of imaging modality, does not affect survival after
      radioembolization. Therefore, hypovascular tumors should not be considered
      contraindicated for radioembolization.

PMID- 19846321
TI  - Nonocclusive "island" of stenosis after suture-mediated arteriotomy closure.

PMID- 19846322
TI  - Hyperhomocysteinaemia, low folate concentrations and methylene tetrahydrofolate
      reductase C677T mutation in acute mesenteric venous thrombosis.
AB  - OBJECTIVES: Acute mesenteric venous thrombosis (AMVT) was first reported by Fagge
      and was recognised as a distinct clinical entity by Warreen in 1935. However, its
      pathogenesis is still unclear. Elevated plasma levels of homocysteine (Hcy) are
      associated with an increased risk of deep vein thrombosis. This case-control
      study examines the potential association among hyperhomocysteinaemia (hyper-Hcy),
      low serum folate and vitamin B(12) levels and the common C677T mutation of the
      MTHFR gene in patients with AMVT. MATERIALS AND METHODS: Sixty-three patients
      with AMVT and 75 sex- and age-matched healthy controls were recruited, and their
      plasma Hcy, folate and vitamin B(12) levels were measured by high performance
      liquid chromatography (HPLC) and immunological assays. The polymorphism of MTHFR
      C677T was detected by PCR-RFLP. RESULTS: The mean plasma Hcy levels were
      significantly higher in patients with AVMT compared with controls (23.5 standard
      deviation (S.D.) 8.8 vs. 12.6+/-6.6micromoll(-1), P<0.01). The fasting Hcy
      correlated negatively with folate (AMVT: r=-0.42, P<0.01; CONTROL: r=-0.40,
      P<0.01). The frequency of homozygous (TT) genotype in MTHFR C677T mutation was
      significantly higher in patients with AMVT than that in control subjects (33% vs.
      17%; chi square (chi(2))=6.31, P<0.05; odds ratio (OR)=2.80; 95% confidence
      interval (CI): 1.25-6.25). Compared with the control subjects, the mean serum
      vitamin B(12) levels were lower in patients, but it was not statistically
      significant (365+/-88pmoll(-1) vs. 408+/-108pmoll(-1), P>0.05). CONCLUSIONS:
      Hyper-Hcy and low serum folate levels were associated with an increased risk of
      AMVT. The homozygous (TT) genotype of MTHFR gene mutation may be a crucial
      hereditary risk factor in the development of AMVT for a Chinese population.

PMID- 19846323
TI  - Behcet extracranial carotid aneurysms: is there still a role for ligation?
AB  - OBJECTIVES: Aneurysm formation in Behcet's disease (BD) rarely involves
      extracranial carotid arteries. We report our experience of the management of
      extracranial carotid artery aneurysms (ECAAs) in BD. MATERIALS AND METHODS: Data
      of patients with Behcet ECAAs presenting from 1997 to 2008 were retrospectively
      collected focusing on the different treatment modalities, the indications for
      each modality and the outcome. RESULTS: Twelve Behcet ECAAs were managed. Seven
      underwent ligation of the carotid artery, where the stump pressure exceeded 70
      mmHg. The remaining five patients underwent vascular reconstruction: either
      excision and reconstruction by an autogenous vein interposition graft (n=3),
      excision and end-to-end anastomosis (n=1), or direct suture of a small rent in
      the artery (n=1). There were no perioperative mortalities or major strokes. There
      was one recurrent laryngeal nerve injury and one hematoma. There was one aneurysm
      recurrence, which was managed by ligation and resulted in a minor stroke.
      CONCLUSION: Surgical repair in Behcet ECAAs should be performed with special
      precautions in order to prevent anastomotic pseudoaneurysm formation. Ligation
      can be performed when the anatomical and/or pathological circumstances are not
      favourable, provided that the stump pressure is adequate to maintain cerebral
      perfusion.

PMID- 19846324
TI  - The prognostic value of panoramic radiography of inferior alveolar nerve damage
      after mandibular third molar removal: retrospective study of 400 cases.
AB  - OBJECTIVE: The aim of the study was to estimate the accuracy of panoramic
      radiographic signs predicting inferior alveolar nerve (IAN) paresthesia after
      lower third molar removal. STUDY DESIGN: In a case-control study the sample was
      composed of 41 cases with postoperative IAN paresthesia and 359 control cases
      without it. The collected data included "classic" specific signs indicating a
      close spatial relationship between third molar root and inferior alveolar canal
      (IAC), root curvatures, and the extent of IAC-root tip overlap. Bivariate and
      multivariate logistic regression analyses were completed to estimate the
      association between radiographic findings and IAN paresthesia. RESULTS: The
      multivariate logistic analysis identified 3 signs significantly associated with
      IAN paresthesia (P < .001): interruption of the superior cortex of the canal
      wall, diversion of the canal, and darkening of the root. The sensitivities and
      specificities ranged from 14.6% to 68.3% and from 85.5% to 96.9%, respectively.
      The positive predictive values, calculated to factor a 1.1% prevalence of
      paresthesia, ranged from 3.6% to 10.9%, whereas the negative predictive values
      >99%. CONCLUSION: Panoramic radiography is an inadequate screening method for
      predicting IAN paresthesia after mandibular third molar removal.

PMID- 19846326
TI  - Evaluation of 18F-FDG PET/CT for diagnosing cervical nodal metastases in patients
      with oral cavity or oropharynx carcinoma.

PMID- 19846327
TI  - Effect of hyperbaric oxygen on demineralized bone matrix and biphasic calcium
      phosphate bone substitutes.
AB  - OBJECTIVES: The aim of this study was to assess the possible effect of hyperbaric
      oxygen (HBO) on the healing of critical-sized defects that were grafted with
      demineralized bone matrix (DBM) combined with Pluronic F127 (F127) to form a gel
      or putty, or a commercially available biphasic calcium phosphate (BCP), mixed
      either with blood or F127 to form a putty. STUDY DESIGN: Twenty New Zealand White
      rabbits were randomly divided into 2 groups of 10 animals each. Bilateral 15-mm
      calvarial defects were created in the parietal bones of each animal, resulting in
      40 critical-sized defects. Group I defects were grafted with either DBM putty or
      DBM gel. Group II defects were grafted with either BCP or BCP putty. Five animals
      from each group received HBO treatment (100% oxygen, at 2.4 ATA) for 90 minutes
      per day 5 days a week for 4 weeks. The other 5 animals in each group served as a
      normobaric (NBO) controls, breathing only room air. All animals were humanely
      killed at 6 weeks. The calvariae were removed and analyzed by micro computed
      tomography (mCT) and histomorphometry. RESULTS: mCT analysis indicated a higher
      bone mineral content (BMC, P < .05), bone volume fraction (BVF; P < .001), and
      bone mineral density (BMD; P < .001) of the defects grafted with BCP rather than
      DBM. Furthermore, the voxels that were counted as bone had a higher tissue
      mineral density (TMD) in the BCP- than in the DBM-filled defects (P < .001).
      Histologically complete bony union over the defects was observed in all
      specimens. Histomorphometric analysis showed that DBM-filled defects had more new
      bone (P < .007) and marrow (P < .001), and reduced fibrous tissue compared with
      the BCP defects (P < .001) under NBO conditions. HBO treatment reduced the amount
      of fibrous tissue in BCP filled defects (P < .05), approaching levels similar to
      that in matching DBM-filled defects. HBO also resulted in a small but significant
      increase in new bone in DBM-grafted defects (P < .05). CONCLUSION: Use of DBM or
      BCP promoted healing in these critical-sized defects. Hyperbaric oxygen therapy
      resulted in a slight increase in new bone in DBM-grafted defects and much larger
      reduction in fibrous tissue and matching increases in marrow in BCP-grafted
      defects, possibly through increased promotion of angiogenesis.

PMID- 19846328
TI  - Setting time and expansion in different soaking media of experimental accelerated
      calcium-silicate cements and ProRoot MTA.
AB  - OBJECTIVES: The setting time and the expansion in deionized water, phosphate
      buffered saline (PBS), 20% fetal bovine serum (FBS)/80% PBS or hexadecane oil of
      experimental accelerated calcium-silicate cements and ProRoot MTA were evaluated.
      STUDY DESIGN: Different compounds such as sodium fluoride, strontium chloride,
      hydroxyapatite, and tricalcium phosphate were separately added to a basic
      experimental calcium-silicate cement to test their effect on setting and
      expansion. The initial and final setting times were determined using appropriate
      Gilmore needles. A linear variable differential transformer (LVDT) device was
      used to test the restricted hygroscopic linear expansion over 180 minutes of
      cements immersed in different solutions. Results were statistically compared
      using a 2-way ANOVA test (cement type versus solution type). RESULTS: All
      experimental cements showed initial setting times between 28 and 45 minutes and
      final setting times between 52 and 80 minutes. MTA showed a final setting time of
      170 minutes. Final setting time of all experimental cements was faster than MTA.
      All cements showed slight (0.04%-0.77%) expansion in water, PBS, or FBS/PBS. Only
      fluoride-containing cement showed a significant expansion in water (6.68%) and in
      PBS (6.72%). The PBS/FBS contamination significantly reduced the expansion of
      fluoride-containing cement (2.98%) and MTA (0.07%). In contrast, cements showed a
      slight shrinkage when immersed in hexadecane, especially fluoride-containing
      cement. CONCLUSIONS: The study demonstrated that: (1) the setting time of calcium
      silicate cements may be effectively reduced; (2) the expansion is a water
      dependent mechanism owing to water uptake, because no expansion occurred in
      cements immersed in oil; (3) a correlation between setting time and expansion in
      water and PBS exists; (4) fluorine-containing cement showed a significant
      expansion in water and in PBS; (5) the immersion in FBS/PBS strongly reduced the
      expansion of MTA and fluoride-doped cement suggesting that fluid contamination
      (ie, blood) during surgical procedures may greatly affect the expansion of some
      calcium-silicate cements.

PMID- 19846329
TI  - Correlation study between distal caries in the mandibular second molar and the
      eruption status of the mandibular third molar in the Korean population.
AB  - OBJECTIVES: The purpose of this study was to analyze the correlation parameters
      between the distal caries of the mandibular second molars (M2Ms) and the eruption
      status of the mandibular third molars (M3Ms). STUDY DESIGN: The records of 786
      patients who had their M3Ms extracted from 2002 to 2007 at Samsung Medical Center
      were reviewed. The distal caries of M2Ms, age, gender, angulations, impaction
      degree, and distance between M2M and M3M were assessed. RESULTS: Among 883 M2Ms,
      152 had distal caries (17.2%, caries group). In the caries group, 79.6% of M3Ms
      exhibited mesial angulation between 40 degrees and 80 degrees and 82.2% of M3Ms
      exhibited an impaction level in which the most coronal aspect of the M3M was
      located superior to the occlusal surface of the M2M. The distance between M2M and
      M3M (between cemontoenamel junctions) was 7-9 mm for 57.2% of the caries group.
      CONCLUSIONS: The M3Ms under eruption status as described here could be considered
      for preventive extraction.

PMID- 19846330
TI  - NK cell lymphoblastic lymphoma in the masticator space: a case of non-Hodgkin
      lymphoma with challenging maxillofacial manifestation and immunophenotype.
AB  - Clinical and pathologic findings in extranodal non-Hodgkin lymphoma (NHL) often
      raise challenging problems in diagnosis. We demonstrate the first established
      case of lymphoma with precursor natural killer (NK) cell origin in the oral and
      maxillofacial region. An 81-year-old Japanese man had an enlarged facial mass
      mainly in the parotid region but hyposensitivity in the affected side of the
      mental and lingual region, and diagnostic imaging revealed the origin to be in
      the masticator space and indicated an advanced-stage lymphoma. The tumor cell
      immunophenotype was CD56(+)CD3(-)CD4(-), with no B-cell- or myeloid-associated
      markers. The genotype was of the germ-line configuration of T-cell receptor
      genes, and no association with Epstein-Barr virus was evident, leading to a
      diagnosis of NK-cell lymphoblastic lymphoma. This report discusses diagnostic
      challenges of NHL, including manifestation of numb chin syndrome as a clinical
      indicator and immunophenotyping of NK-cell-lineage neoplasms.

PMID- 19846331
TI  - Bovine viral diarrhoea virus: economic evaluation of outbreaks by modelling.

PMID- 19846332
TI  - A timeline for Parkinson's disease.
AB  - It is reasonably well established that prior to the motor phase of classical
      Parkinson's disease (PD) there is a prodromal period of several years duration.
      Once typical motor features appear, the disease continues up to 20 years
      depending on multiple variables. The clinical features of the prodromal and motor
      phases may be correlated with pathological changes in the central and autonomic
      nervous systems to allow a sequential plan of disease progression. We present a
      'best guess' for a typical individual presenting with PD in their sixties and
      speculate that the disease will last approximately 40 years from the earliest non
      motor features to death. Appreciation of this concept may allow better strategies
      for slowing or halting disease progression.

PMID- 19846333
TI  - Outsourcing neuroimaging data analysis Implications for scientific accountability
      and issues in the public interest.

PMID- 19846334
TI  - Cellular processes relying on sterol function in plants.
AB  - Sterols are lipophilic membrane components essential for diverse cellular
      functions. The plant sterol biosynthesis pathway has largely been defined by
      biochemical approaches. Sterol function has been investigated by the
      pharmacological and genetic manipulation of sterol biosynthesis. However,
      mechanisms by which sterols influence cellular processes and targets of sterol
      function remain largely unknown. During the last two years, new Arabidopsis
      sterol biosynthesis mutants have been characterized. Their analysis has revealed
      the contributions of known and alternative routes of sterol biosynthesis to
      various cellular processes. Subcellular localization and trafficking of a sterol
      binding protein have been investigated and first steps towards in vivo
      characterization of sterol-enriched membrane domains have been taken. Finally,
      mechanistic insight into the role of plant sterols during endocytosis and the
      establishment of cell polarity has been obtained.

PMID- 19846335
TI  - Conservation and divergence of centromere specification in yeast.
AB  - Centromeres are specialized structures on eukaryotic chromosomes that couple
      chromosome movements to spindle microtubule movements and allow accurate
      chromosome segregation during cell division. In spite of these vital functions,
      recent evidence strongly suggests that epigenetic regulation rather than the
      primary DNA sequence of the centromere plays a dominant role in the specification
      of centromeres. The key determinant of centromere identity is the centromere
      specific histone H3 variant CENP-A (also known as CenH3). This review highlights
      exciting new findings examining the mechanism of centromere specification in
      distinct yeast species, which provides insights into CENP-A nucleosome assembly
      and establishment of centromere identity.

PMID- 19846336
TI  - Persistent adenoviraemia in an infant following haematopoietic stem cell
      transplantation.

PMID- 19846337
TI  - Multifocal frequency-doubling pattern visual evoked responses to dichoptic
      stimulation.
AB  - OBJECTIVE: To examine the feasibility of a multifocal visual evoked potential
      (mfVEP) binocularly, using a variant of the multifocal frequency-doubling (FD)
      pattern-electroretinogram (MFP). METHODS: Stimuli were presented in both
      monocular and dichoptic conditions at eight visual field locations/eye. The
      incommensurate stimulus frequencies ranged from 15.45 to 21.51 Hz. Five stimulus
      conditions differing in spatial frequency and orientation were examined for three
      viewing conditions. The resulting 15 stimulus conditions were examined in 16
      normal subjects who repeated all conditions twice. RESULTS: Several significant
      independent effects were identified. Response amplitudes were reduced for
      dichoptic viewing (by 0.85 times, p<4 x 10(-11)); offset by increases in
      responses for between eye differences of one octave of spatial frequency: lower
      (1.15 times, 0.1 cpd); higher (1.29 times, 0.4 cpd), both p<1.8 x 10(-7). Crossed
      orientations produced significant effects upon response phase (p=0.023) but not
      amplitude (p=0.062). CONCLUSIONS: The results indicated that dichoptic evoked
      potentials using multifocal frequency-doubling illusion stimuli are practical.
      The use of crossed orientation, or differing spatial frequencies, in the two eyes
      reduced binocular interactions. SIGNIFICANCE: The results indicate a method
      wherein several spatial or temporal and frequencies per visual field region can
      be tested in reasonable time using a multifocal VEP using spatial frequency
      doubling stimuli.

PMID- 19846338
TI  - Sodium oxybate is an effective and safe treatment for narcolepsy.

PMID- 19846340
TI  - Opioid-receptor-heteromer-specific trafficking and pharmacology.
AB  - Homomerization and heteromerization of 7 transmembrane spanning (7TM)/G-protein
      coupled receptors (GPCRs) have been an important field of study. Whereas initial
      studies were performed in artificial cell systems, recent publications are
      shifting the focus to the in vivo relevance of heteromerization. This is
      especially apparent for the field of opioid receptors. Drugs have been identified
      that selectively target opioid heteromers of the delta-opioid receptor with the
      kappa and the mu-opioid receptors that influence nociception and ethanol
      consumption, respectively. In addition, in several cases, the specific
      physiological response produced by the heteromer may be directly attributed to a
      difference in receptor trafficking properties of the heteromers compared with
      their homomeric counterparts. This review attempts to highlight some of the
      latest developments with regard to opioid receptor heteromer trafficking and
      pharmacology.

PMID- 19846341
TI  - Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells.
AB  - Immunity in the newborn is characterized by minimal T helper (Th)1 function but
      an excess of Th2 activity. Since Th1 lymphocytes are important to counter
      microbes and Th2 cells favor allergies, the newborn faces susceptibility to
      microbial infections and allergic reactions. Delayed maturation of certain
      dendritic cells leads to limited interleukin (IL)-12 production during the
      neonatal period. The Th2 cytokine locus of neonatal CD4(+) T cells is poised
      epigenetically for rapid and robust production of IL-4 and IL-13. Together, these
      circumstances lead to efficient differentiation of Th2 cells and the expression
      of an IL-4Ralpha/IL-13Ralpha1 heteroreceptor on Th1 cells. Upon re-challenge, Th2
      cells rapidly produce IL-4 which utilizes the heteroreceptor to drive apoptosis
      of Th1 cells, thus yielding the Th2 bias of neonatal immunity.

PMID- 19846342
TI  - Strategies for targeted nonviral delivery of siRNAs in vivo.
AB  - Silencing specific gene expression by RNA interference (RNAi) has rapidly become
      a standard tool for the reverse genetic analysis of gene functions. It also has
      tremendous potential for managing diseases for which effective treatment is
      currently unavailable or suboptimal. However, the poor cellular uptake of
      synthetic small interfering RNAs (siRNAs) is a major impediment for their
      clinical use. Great progress has been made in recent years to overcome this
      barrier, and several methods have been described for the in vivo delivery of
      siRNA. Moreover, the latest advances have focused on achieving targeted siRNA
      delivery restricted to relevant tissues and cell types in vivo. These approaches
      are expected to reduce the dose requirement as well as minimize siRNA-induced
      toxicities, thereby advancing the field of siRNA therapy towards clinical use.

PMID- 19846343
TI  - Preprocedural concerns and anxiety assessment in patients undergoing coronary
      angiography and percutaneous coronary interventions.
AB  - BACKGROUND: Patients with anxiety prior to coronary angiography and percutaneous
      coronary intervention (PCI), may have negative physical and psychological
      consequences. AIM: To identify patients factors associated with anxiety and
      assess the validity of the Faces Anxiety Scale (FAS) in this sample. METHODS:
      Patients (n=159) were surveyed preprocedure using the Spielberger State Anxiety
      Inventory (SAI) and the FAS and asked to identify their major concern. RESULTS:
      The sample was aged an average 66.73 years (sd 10.12) and predominantly male
      (72%). Anxiety was low to moderate (SAI mean 36.44, sd 11.23; FAS median 2, range
      1-5). There was a moderate correlation between the SAI and the FAS (r=.521,
      p=or<.001), with the FAS having low sensitivity (27%) and high specificity (95%).
      Patients' most common concern (37%) was uncertainty about the outcome from the
      procedure. Predictors of higher anxiety were taking medication for anxiety or
      depression (beta=5.84), experiencing angina (beta=4.96) or having a major concern
      about the procedural outcome (beta=4.00). CONCLUSIONS: Many patients have
      moderate anxiety before coronary angiography and PCI; therefore, routine
      assessment and management of anxiety are justified. The FAS is not as useful as
      the SAI for this purpose.

PMID- 19846345
TI  - Ictal flatulence: seizure onset in the nondominant hemisphere.
AB  - We describe the case of a 45-year-old woman with frequent simple partial seizures
      consisting mainly of autonomic manifestations including flatulence. The ictal
      onset and interictal EEG epileptiform abnormalities were localized to the right
      frontotemporal region. This localization was supported by structural brain
      imaging showing recurrence of a right frontotemporal oligodendroglioma with
      involvement of the insula. We therefore suggest that ictal flatulence is one of
      several autonomic and gastrointestinal symptoms and signs that may be used
      clinically in lateralizing to the nondominant hemisphere.

PMID- 19846344
TI  - Influenza vaccine administration in rheumatoid arthritis patients under treatment
      with TNFalpha blockers: safety and immunogenicity.
AB  - Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under
      treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at
      least once with non-adjuvanted trivalent influenza vaccine during three
      consecutive influenza seasons. Antibodies toward A influenza antigens
      significantly increased and reached protective levels, still detectable 6 months
      after vaccination, both in RA patients and healthy controls. Response to B
      antigen instead was only observed from the second year for healthy controls and
      in the third year for patients. No significant difference in disease activity and
      anti-nuclear antibodies was observed as a consequence of vaccine administration,
      whereas T regulatory cells showed a significant increase 30 days after
      immunization in RA patients. This study confirms safety of influenza vaccine
      administration in RA patients treated with TNFalpha blockers. The cohort follow
      up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated
      vaccinations. Finally, protective antibody response was still observed 6 months
      after vaccination.

PMID- 19846347
TI  - Physical derivation of nomograms in permanent prostate brachytherapy.
AB  - PURPOSE: To demonstrate the physical origin of nomograms in permanent prostate
      brachytherapy, by using the correlation between fractional integral target dose
      (FITD) and target volume. METHODS AND MATERIALS: The integral dose (ID) E
      delivered by unit activity is given by the integration of 4pi r(2)D(r)/r(2)dr x
      1.44T(1/2) using the point source model from AAPM TG43. If A is the total
      activity implanted, then total ID will be AxE. Integral target dose are obtained
      by multiplying the prostate volume V with mean dose D(mean) by definition,
      assuming prostate gland has a unity density. The FITD the target receives is
      defined as FITD=D(mean)V/AE by energy conservation in the target volume. From
      this equation, the total activity needed to achieve given dose for a target of
      volume V is obtained. Results are compared with existing nomograms for (125)I and
      (103)Pd, and available clinical data for (131)Cs. RESULTS: Agreement within 10.0%
      for (125)I and (103)Pd compared with existing nomograms for gland sizes from 18
      to 80 cc is observed. For (131)Cs, the agreement is within 8.0% compared with
      available clinical data. CONCLUSIONS: It is shown that the correlation between
      the FITD and target volume can be used to obtain the total activity needed to
      achieve prescribed dose. This correlation is inherent rather than empirical. It
      suggests that the correlation between fraction of energy deposition in target and
      target volume is the underlying physical origin for nomograms used in permanent
      prostate brachytherapy.

PMID- 19846346
TI  - High-dose-rate surface brachytherapy to boost elongated, curvilinear incisional
      scars after extrapleural pneumonectomy for malignant pleural mesothelioma treated
      with adjuvant intensity-modulated radiation therapy.
AB  - PURPOSE: Providing adequate dosimetric coverage of elongated, curvilinear
      incisions during adjuvant intensity-modulated radiation therapy (IMRT) after
      extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) creates
      technical challenges. We explored high-dose-rate (HDR) surface brachytherapy to
      supplement dose to multiple curvilinear incisions. This modality circumvents the
      technical limitations of relying on multiple en face electron fields while
      minimizing dose to adjacent normal tissues. METHODS AND MATERIALS: A 59-year-old
      man presented with a left-sided, Stage III, T3N2M0, epithelioid MPM. After
      undergoing a left EPP, adjuvant IMRT was recommended to improve local control. An
      eight-field IMRT plan was designed to encompass the postoperative hemithorax.
      Incisional scars were lengthy and extended beyond the hemithoracic target volume.
      Both en face electron and surface HDR plans were prepared and evaluated based on
      dosimetric coverage of the incisional scars, dose to normal tissues, reliability
      of setup, and treatment delivery. RESULTS: HDR was preferred. The patient was
      planned and treated in the right lateral decubitus position. HDR source catheters
      were placed along the incisions atop 5-mm bolus. A composite plan including IMRT
      and brachytherapy dose contributions was produced. Boosts of incisional scars
      were performed in six fractions (three fractions per week) of 3 Gy prescribed to
      12 mm from the catheter. HDR brachytherapy was well tolerated. CONCLUSIONS:
      Surface HDR brachytherapy is a viable option for supplemental dose to incisional
      scars at risk of local recurrence after EPP for MPM. Advantages over electron
      beam therapy include avoidance of field abutments and feathering, less tissue
      bone interface dose uncertainty and reproducibility of treatment delivery.

PMID- 19846348
TI  - High-dose-rate brachytherapy in combination with conformal external beam
      radiotherapy in the treatment of prostate cancer.
AB  - PURPOSE: To report long-term outcomes for treatment of prostate cancer using dose
      escalation with high-dose-rate (HDR) brachytherapy and 3-dimensional conformal
      external beam radiotherapy (3DCRT), and compare them with outcomes for treatment
      of prostate cancer with 3DCRT alone at the same institution. METHODS AND
      MATERIALS: From 1998 to 2003, 587 patients were treated for clinically localized
      prostate cancer. Patients received either 3DCRT (median, 46Gy) with a single HDR
      brachytherapy implant (196 patients) delivering a fractionated dose of 18Gy
      (combined group) or 3DCRT (median, 70Gy; 387 patients; "3DCRT alone"). There were
      41.9% patients with intermediate-risk and 42.6% with high-risk disease. In all,
      441 patients (75.1%) received neoadjuvant and 116 patients (19.8%) received
      adjuvant androgen deprivation therapy. The American Society of Therapeutic
      Radiology and Oncology Phoenix definition for biochemical failure was used.
      RESULTS: The median followup was 5.5 years. The 5- and 7-year biochemical control
      (BC) rates were 82.5% and 80.3%, respectively, for the combined group and 81.3%
      and 71%, respectively, for 3DCRT alone; for overall survival, they were 91.9% and
      89.5% vs. 88.7% and 86.2%, respectively, whereas for cause-specific survival,
      they were 96.9% and 96.1% vs. 97.6% and 96.2%, respectively. Cox proportional
      hazard regression analysis for BC revealed that low Gleason grade, HDR
      brachytherapy combined with 3DCRT, and adjuvant androgen deprivation therapy were
      significant in predicting BC. Radiation Therapy Oncology Group Grade 3 late
      urinary and rectal morbidity rates were 7.1% and 0%, respectively. No Grade > or
      =4 reactions were detected. CONCLUSIONS: HDR brachytherapy combined with 3DCRT
      was associated with improved BC and minimal toxicity in patients with unfavorable
      prostate cancer compared with conventional 3DCRT.

PMID- 19846349
TI  - High-dose-rate afterloading intraluminal brachytherapy for advanced inoperable
      rectal carcinoma.
AB  - PURPOSE: High-dose-rate (HDR) intraluminal brachytherapy for advanced or
      inoperable tumors of the rectum has been used both palliatively and to dose
      escalate after chemoradiation for curative treatment. METHODS: Between 1993 and
      2007, 79 patients were treated with HDR afterloading brachytherapy for rectal
      cancer; 70 patients had adenocarcinoma of the rectum; and 9 patients had squamous
      cell carcinoma of the anal canal. Fifty-two patients had localized disease but
      were unfit for major surgery and received radiotherapy with radical intent.
      Twenty-seven patients with advanced or metastatic disease received palliative
      treatment. The median age was 82 years (range, 33-97). Radical treatment
      comprised either chemoradiation followed by intraluminal brachytherapy delivering
      12 Gy at 1 cm in two fractions or radical monotherapy delivering up to 36 Gy at 1
      cm in six fractions two to three times weekly. Palliative HDR brachytherapy
      schedules were predominantly 10 Gy at 1 cm single dose. RESULTS: Objective local
      tumor response was seen in 41 of 48 assessable patients (85%); of whom, 28
      patients (58%) had a complete response and 13 (27%) had a partial response. The
      most common symptom was rectal bleeding, which was controlled with a complete
      response rate of 63%. The median duration of the symptom response was 3 months
      (range, 1-73), and the median survival of the palliative patients was 6 months
      (range, 1 week-37 months). The median survival for patients treated with radical
      intent was 18.5 months (range, 2-119). Six patients reported late toxicity with
      three cases of rectal ulcer, two strictures, and one fistula. CONCLUSIONS:
      Intraluminal HDR brachytherapy is effective as local treatment in both the
      radical and palliative setting, with high tumor and symptom response rates, and
      acceptable late toxicity.

PMID- 19846350
TI  - Relationship between Day 0 dosimetric parameters and biochemical relapse-free
      survival in patients treated with transperineal permanent prostate interstitial
      brachytherapy with (125)I seeds.
AB  - OBJECTIVES: To determine the relationship between dosimetric parameters obtained
      on postimplantation Day 0 and biochemical relapse-free survival (bRFS) in
      patients treated with (125)I transperineal interstitial permanent prostate
      brachytherapy (TIPPB). METHODS: Two-hundred twenty men with low-risk (n=155,
      70.4%), low-volume intermediate-risk (n=63, 28.7%), or high-risk (n=2, 0.9%)
      prostate cancer were treated with TIPPB between December 2000 and June 2006.
      Seventy-four (33.6%) patients received short-term (3-6 months) androgen
      suppression therapy before TIPPB. The median followup for patients free of
      biochemical failure was of 37.9 months (range, 24.0-84.5 months). RESULTS: The
      receiver operating characteristic (ROC) analysis established a best-fit cutoff
      value for the quantifiers D(90) and V(100) of 147Gy and 92%, respectively. The
      Kaplan-Meier analysis of bRFS at the cutoff value of D(90)=147Gy using the ASTRO,
      nadir+2, and combined (ASTRO and nadir+2) definitions showed a trend toward
      statistical significance for the ASTRO (p=0.076) and nadir+2 (p=0.064)
      definitions and a statistically significant correlation for the combined
      definition (p=0.033). The corresponding 7-year bRFS for the D(90) >147Gy and
      D(90) </=147Gy subsets using the ASTRO, nadir+2, and combined definitions were
      96.5% vs. 89.7% (ASTRO, p=0.076); 93.7% vs. 70.5% (nadir+2, p=0.064); and 94.4
      vs. 75.5% (combined, p=0.033). The V(100) (%) cutoff value of 92% predicted by
      the ROC analysis was not significant. Among other cutoff values, only D(90)=140Gy
      (p=0.050) and D(90)=160Gy (p=0.098) showed a trend toward statistical
      significance when the nadir+2 and the ASTRO definitions were used. The rest of
      dosimetric, tumor, and patient parameters did not show statistical correlation
      with bRFS in the Kaplan-Meier analysis. CONCLUSIONS: The cutoff value of
      D(90)=147Gy obtained on postimplantation Day 0 showed a trend toward significant
      correlation with bRFS when the standard ASTRO and nadir+2 definitions were used
      and a weak but statistically significant correlation with bRFS as per the
      nonstandard combined definition in a series of patients with predominantly low
      risk disease (70.4%) treated at high radiation doses (median D(90)=152.9Gy,
      median V(100)=92.5%).

PMID- 19846351
TI  - Diabetes remission and reduced cardiovascular risk after gastric bypass in Asian
      Indians with body mass index <35 kg/m(2).
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) benefits patients with type 2
      diabetes mellitus (T2DM) and a body mass index (BMI) >35 kg/m(2); however, its
      effectiveness in patients with T2DM and a BMI <35 kg/m(2) is unclear. Asian
      Indians have a high risk of T2DM and cardiovascular disease at relatively low BMI
      levels. We examined the safety and efficacy of RYGB in Asian Indian patients with
      T2DM and a BMI of 22-35 kg/m(2) in a tertiary care medical center. METHODS: A
      total of 15 consecutive patients with T2DM and a BMI of 22-35 kg/m(2) underwent
      RYGB. The data were prospectively collected before surgery and at 1, 3, 6, and 9
      months postoperatively. RESULTS: Of the 15 patients, 8 were men and 7 were women
      (age 45.6 +/- 12 years). Their preoperative characteristics were BMI 28.9 +/- 4.0
      kg/m(2), body weight 78.7 +/- 12.5 kg, waist circumference 100.2 +/- 6.8 cm, and
      duration of T2DM 8.7 +/- 5.3 years. At baseline, 80% of subjects required
      insulin, and 20% controlled their T2DM with oral hypoglycemic medication. The BMI
      decreased postoperatively by 20%, from 28.9 +/- 4.0 kg/m(2) to 23.0 +/- 3.6
      kg/m(2) (P <.001). All antidiabetic medications were discontinued by 1 month
      after surgery in 80% of the subjects. At 3 months and thereafter, 100% were
      euglycemic and no longer required diabetes medication. The fasting blood glucose
      level decreased from 233 +/- 87 mg/dL to 89 +/- 12 mg/dL (P <.001), and the
      hemoglobin A1c decreased from 10.1% +/- 2.0% to 6.1% +/- 0.6% (P <.001). Their
      waist circumference, presence of dyslipidemia, and hypertension improved
      significantly. The predicted 10-year cardiovascular disease risk (calculated
      using the United Kingdom Prospective Diabetes Study equations) decreased
      substantially for fatal and nonfatal coronary heart disease and stroke. No
      mortality, major surgical morbidity, or excessive weight loss occurred.
      CONCLUSION: RYGB safely and effectively eliminated T2DM in Asian Indians with a
      BMI <35 kg/m(2). Larger, longer term studies are needed to confirm this benefit.

PMID- 19846352
TI  - Electrochemistry of norepinephrine on carbon-coated nickel magnetic nanoparticles
      modified electrode and analytical applications.
AB  - A carbon-coated nickel magnetic nanoparticles modified glassy carbon electrode (C
      Ni/GCE) was fabricated. The carbon-coated nickel magnetic nanoparticles were
      characterized with transmission electron microscopy (TEM). The electrochemical
      behaviors of norepinephrine (NE) were investigated on the modified electrode by
      cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The carbon
      coated nickel magnetic nanoparticles showed excellent electrocatalytic activity
      for the electrochemical redox of NE. NE exhibited two couples of well-defined
      redox peaks on C-Ni/GCE over the potential range from -0.4 to 0.8V in phosphate
      buffer solution (PBS) (pH=7.0). The redox mechanism for NE was proposed. DPV
      response of NE on the C-Ni/GCE showed that the catalytic oxidative peak current
      was linear with the square root concentration of NE in the range of 2.0 x 10(-7)
      to 8.0 x 10(-5)M, with a detection limit of 6.0 x 10(-8)M. The C-Ni/GCE showed
      good sensitivity, selectivity and stability for the determination of NE.

PMID- 19846353
TI  - A soluble RecN homologue provides means for biochemical and genetic analysis of
      DNA double-strand break repair in Escherichia coli.
AB  - RecN is a highly conserved, SMC-like protein in bacteria. It plays an important
      role in the repair of DNA double-strand breaks and is therefore a key factor in
      maintaining genome integrity. The insolubility of Escherichia coli RecN has
      limited efforts to unravel its function. We overcame this limitation by replacing
      the resident coding sequence with that of Haemophilus influenzae RecN. The
      heterologous construct expresses Haemophilus RecN from the SOS-inducible E. coli
      promoter. The hybrid gene is fully functional, promoting survival after I-SceI
      induced DNA breakage, gamma irradiation or exposure to mitomycin C as effectively
      as the native gene, indicating that the repair activity is conserved between
      these two species. H. influenzae RecN is quite soluble, even when expressed at
      high levels, and is readily purified. Its analysis by ionisation-mass
      spectrometry, gel filtration and glutaraldehyde crosslinking indicates that it is
      probably a dimer under physiological conditions, although a higher multimer
      cannot be excluded. The purified protein displays a weak ATPase activity that is
      essential for its DNA repair function in vivo. However, no DNA-binding activity
      was detected, which contrasts with RecN from Bacillus subtilis. RecN proteins
      from Aquifex aeolicus and Bacteriodes fragilis also proved soluble. Neither binds
      DNA, but the Aquifex RecN has weak ATPase activity. Our findings support studies
      indicating that RecN, and the SOS response in general, behave differently in E.
      coli and B. subtilis. The hybrid recN reported provides new opportunities to
      study the genetics and biochemistry of how RecN operates in E. coli.

PMID- 19846355
TI  - Efficacy of four different moxifloxacin-based triple therapies for first-line H.
      pylori treatment.
AB  - Moxifloxacin has been used in the first-line treatment of Helicobacter pylori
      infection. The optimal dosage and duration have not been assessed. AIM: To
      evaluate the effectiveness of moxifloxacin, amoxicillin and esomeprazole in four
      regimens, in previously untreated patients infected by H. pylori. METHODS AND
      PATIENTS: Patients were randomly assigned to: esomeprazole 20 mg b.i.d.,
      amoxicillin 1g b.i.d., and one of each of the four following dosages of
      moxifloxacin: moxifloxacin 400 mg b.i.d. for 10 days (EAM800x10), moxifloxacin
      400 mg b.i.d. for 7 days (EAM800x7), moxifloxacin 400 mg b.i.d. for 5 days
      (EAM800x5), moxifloxacin 400 mg o.i.d. for 10 days (EAM400x10). Eradication was
      assessed by the Urea Breath Test (UBT) 2 months following the end of therapy.
      RESULTS: Ninety-four, 102, 92 and 105 patients were recruited in EAM800x10,
      EAM800x7, EAM800x5, and EAM400x10 respectively. The eradication rate was for
      Intention-To-Treat (ITT) and Per Protocol (PP) analyses: EAM800x10 group ITT:
      90.4%, PP: 94.4%; EAM800x7 group ITT: 80.3%, PP: 86.3%; EAM800x5 group ITT:
      71.4%, PP: 75.2%; EAM400x10 group ITT: 80.0%, PP 84.8%. A statistically
      significant difference was reached between EAM800x10 vs. EAM800x7 (ITT and PP:
      P<0.05), and between EAM800x10 vs. EAM800x5 (ITT and PP: P<0.01) and vs.
      EAM400x10 (ITT: P<0.05; PP: P<0.04). Thirty patients treated unsuccessfully with
      EAM800x5 and EAM400x10 were re-treated with EAM800x10 with an eradication rate of
      86.7% (ITT) and 92.2% (PP). Nineteen patients with positive UBT after EAM800x10
      and EAM800x7 underwent a second-line rifabutin-based therapy with an eradication
      rate of 84.2% (ITT and PP). CONCLUSION: A triple therapy with 800 mg of
      moxifloxacin a day for 10 days is more effective than the same treatment for 5 or
      7 days and a treatment with 400mg of moxifloxacin a day for 10 days for the first
      line eradication of H. pylori infection. The high cost of moxifloxacin-based
      treatment however, may limit its wide use as first-line treatment of H. pylori
      infection.

PMID- 19846354
TI  - Immunotherapy in the landscape of new targeted treatments for non-small cell lung
      cancer.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death
      worldwide. Active immunotherapies and molecules targeting tyrosine kinase
      receptors both offer new avenues for the treatment of NSCLC. Furthermore, their
      combinations or their administration along with standard treatments enlarges the
      potential for clinical benefit. Moreover, the discovery of biomarkers predicting
      the response to these new therapies should allow a better selection of patients
      susceptible to optimally benefit from these treatments. In this paper, we review
      the most promising active immunotherapies, antibodies and small molecules in the
      context of NSCLC management, focusing on compounds in phase III clinical
      development.

PMID- 19846356
TI  - Development and psychometric evaluation of a quantitative measure of "fat talk".
AB  - Based on her anthropological research, Nichter (2000) concluded that it is
      normative for many American girls to engage in body self-disparagement in the
      form of "fat talk." The purpose of the present two studies was to develop a
      quantitative measure of fat talk. A series of 17 scenarios were created in which
      "Naomi" is talking with a female friend(s) and there is an expression of fat
      talk. College women respondents rated the frequency with which they would behave
      in a similar way as the women in each scenario. A nine-item one-factor scale was
      determined through principal components analysis and its scores yielded evidence
      of internal consistency reliability, test-retest reliability over a five-week
      time period, construct validity, discriminant validity, and incremental validity
      in that it predicted unique variance in body shame and eating disorder symptoms
      above and beyond other measures of self-objectification.

PMID- 19846357
TI  - Retained VAC therapy sponge as a complication of abdominoplasty.

PMID- 19846358
TI  - Decompression of the ulnar nerve and minimal medial epicondylectomy with a small
      incision for cubital tunnel syndrome: comparison with anterior subcutaneous
      transposition of the nerve.
AB  - The objective of this study is to compare the results of ulnar nerve
      decompression and minimal medial epicondylectomy with a small incision (group I)
      and anterior subcutaneous transposition of the ulnar nerve (group II) for cubital
      tunnel syndrome. METHODS: Out of 56 patients with cubital tunnel syndrome, 29
      were in group I and 27 were in group II. The mean age at the time of the
      operation was 48.9 years, and the mean follow-up period was 36.4 months.
      Preoperatively, the neuropathy was graded according to Dellon's criteria.
      RESULTS: There were no significant differences between the results of the two
      groups according to the modified Bishop's system at the last follow-up. However,
      four patients showed painful neuroma around the operation scar and one patient in
      group II had experienced acute deterioration of the symptoms after the procedure.
      CONCLUSIONS: Decompression and minimal medial epicondylectomy with a small
      incision seems to be more recommendable than anterior subcutaneous transposition
      of the ulnar nerve for cubital tunnel syndrome in terms of its simplicity and
      lesser invasiveness.

PMID- 19846359
TI  - The value of intermittent cervical traction in recent cervical radiculopathy.
AB  - OBJECTIVE: Our objective is to assess the effect of mechanical and manual
      intermittent cervical traction on pain, use of analgesics and disability during
      the recent cervical radiculopathy (CR). METHODS: We made a prospective randomized
      study including patients sent for rehabilitation between April 2005 and October
      2006. Thirty-nine patients were divided into three groups of 13 patients each. A
      group (A) treated by conventional rehabilitation with manual traction, a group
      (B) treated with conventional rehabilitation with intermittent mechanical
      traction and a third group (C) treated with conventional rehabilitation alone. We
      evaluated cervical pain, radicular pain, disability and the use of analgesics at
      baseline, at the end and at 1, 3 and 6 months after treatment. RESULTS: At the
      end of treatment improving of cervical pain, radicular pain and disability is
      significantly better in groups A and B compared to group C. The decrease in
      consumption of analgesics is comparable in the three groups. At 6 months
      improving of cervical and radicular pain and disability is still significant
      compared to baseline in both groups A and B. The gain in consumption of
      analgesics is significant in the three groups: A, B and C. CONCLUSION: Manual or
      mechanical cervical traction appears to be a major contribution in the
      rehabilitation of CR particularly if it is included in a multimodal approach of
      rehabilitation.

PMID- 19846360
TI  - Tobacco, alcohol and tea drinking as risk factors for esophageal cancer: A case
      control study from Mumbai, India.
AB  - Esophageal cancer is a relatively rare form of cancer, but some world areas have
      a markedly higher incidence than others: China, Iceland, India, Japan and United
      Kingdom, appear to have a higher incidence, as well as the region around the
      Caspian Sea. In India the incidence rates vary across the country. Despite higher
      incidence rate, there are only few studies from the Indian subcontinent. This
      study conducted at Tata Memorial hospital, Mumbai, India, included 442 cases of
      esophageal cancer and 1628 hospital controls. Data was collected on chewing,
      smoking, alcohol habits and dietary habits. The results indicated a moderate 1.1
      times excess risk for chewers of pan (betel-leaf) with tobacco, 1.8-fold excess
      risk for bidi smokers and 2-fold for cigarette smokers, and 1.8-fold excess risk
      for alcohol drinkers. There was a clear dose-response relationship in those with
      the habits. Among the beverages, tea drinking, common in India, showed a 4-fold
      excess risk for esophageal cancer. However fresh-fish showed a 20% reduction in
      risk for esophageal cancer. Besides several other risk factors, these may be
      studied in the Indian set-up which has a heterogeneous population with a varied
      life-style and dietary habits. This could give indicators for prevention.

PMID- 19846362
TI  - In vivo validation of a hybrid tracking system for navigation of an ultrathin
      bronchoscope within peripheral airways.
AB  - Transbronchial biopsy of peripheral lung nodules is hindered by the inability to
      access lesions endoluminally due to the large diameter of conventional
      bronchoscopes. An ultrathin scanning fiber bronchoscope has recently been
      developed to advance image-guided biopsy several branching generations deeper
      into the peripheral airways. However, navigating a potentially complex 3-D path
      to the region of interest presents a challenge to the bronchoscopist. An
      accompanying guidance system has also been developed to track the bronchoscope
      through the airways, and display its position and intended path on a virtual
      display. Intraoperative localization of the bronchoscope was achieved by
      combining electromagnetic tracking (EMT) and image-based tracking (IBT). An error
      state Kalman filter was used to model the disagreement between the two tracking
      sources. The positional tracking error was reduced from 14.22 and 14.92 mm by
      independent EMT and IBT, respectively, to 6.74 mm using the hybrid approach.
      Hybrid tracking of the scope orientation and respiratory motion compensation
      further improved tracking accuracy and stability, resulting in an average
      tracking error of 3.33 mm and 10.01 degrees.

PMID- 19846361
TI  - Multiclass real-time intent recognition of a powered lower limb prosthesis.
AB  - This paper describes a control architecture and intent recognition approach for
      the real-time supervisory control of a powered lower limb prosthesis. The
      approach infers user intent to stand, sit, or walk, by recognizing patterns in
      prosthesis sensor data in real time, without the need for instrumentation of the
      sound-side leg. Specifically, the intent recognizer utilizes time-based features
      extracted from frames of prosthesis signals, which are subsequently reduced to a
      lower dimensionality (for computational efficiency). These data are initially
      used to train intent models, which classify the patterns as standing, sitting, or
      walking. The trained models are subsequently used to infer the user's intent in
      real time. In addition to describing the generalized control approach, this paper
      describes the implementation of this approach on a single unilateral transfemoral
      amputee subject and demonstrates via experiments the effectiveness of the
      approach. In the real-time supervisory control experiments, the intent recognizer
      identified all 90 activity-mode transitions, switching the underlying middle
      level controllers without any perceivable delay by the user. The intent
      recognizer also identified six activity-mode transitions, which were not intended
      by the user. Due to the intentional overlapping functionality of the middle-level
      controllers, the incorrect classifications neither caused problems in
      functionality, nor were perceived by the user.

PMID- 19846363
TI  - Comparison study of three different image reconstruction algorithms for MAT-MI.
AB  - In this paper, we report a theoretical study on magnetoacoustic tomography with
      magnetic induction (MAT-MI). According to the description of signal generation
      mechanism using Green's function, the acoustic dipole model was proposed to
      describe acoustic source excited by the Lorentz force. Using Green's function,
      three kinds of reconstruction algorithms based on different models of acoustic
      source (potential energy, vectored acoustic pressure, and divergence of Lorenz
      force) are deduced and compared, and corresponding numerical simulations were
      conducted to compare these three kinds of reconstruction algorithms. The computer
      simulation results indicate that the potential energy method and vectored
      pressure method can directly reconstruct the Lorentz force distribution and give
      a more accurate reconstruction of electrical conductivity.

PMID- 19846364
TI  - Improved volumetric MR-HIFU ablation by robust binary feedback control.
AB  - Volumetric high-intensity focused ultrasound (HIFU) guided by multiplane magnetic
      resonance (MR) thermometry has been shown to be a safe and efficient method to
      thermally ablate large tissue volumes. However, the induced temperature rise and
      thermal lesions show significant variability, depending on exposure parameters,
      such as power and timing, as well as unknown tissue parameters. In this study, a
      simple and robust feedback-control method that relies on rapid MR thermometry to
      control the HIFU exposure during heating is introduced. The binary feedback
      algorithm adjusts the durations of the concentric ablation circles within the
      target volume to reach an optimal temperature. The efficacy of the binary
      feedback control was evaluated by performing 90 ablations in vivo and comparing
      the results with simulations. Feedback control of the sonications improved the
      reproducibility of the induced lesion size. The standard deviation of the
      diameter was reduced by factors of 1.9, 7.2, 5.0, and 3.4 for 4-, 8-, 12-, and 16
      mm lesions, respectively. Energy efficiency was also improved, as the binary
      feedback method required less energy to create the desired lesion. These results
      show that binary feedback improves the quality of volumetric ablation by
      consistently producing thermal lesions of expected size while reducing the
      required energy as well.

PMID- 19846365
TI  - Microbubble-size dependence of focused ultrasound-induced blood-brain barrier
      opening in mice in vivo.
AB  - The therapeutic efficacy of neurological agents is severely limited, because
      large compounds do not cross the blood-brain barrier (BBB). Focused ultrasound
      (FUS) sonication in the presence of microbubbles has been shown to temporarily
      open the BBB, allowing systemically administered agents into the brain. Until
      now, polydispersed microbubbles (1-10 microm in diameter) were used, and,
      therefore, the bubble sizes better suited for inducing the opening remain
      unknown. Here, the FUS-induced BBB opening dependence on microbubble size is
      investigated. Bubbles at 1-2 and 4-5 microm in diameter were separately size
      isolated using differential centrifugation before being systemically administered
      in mice (n = 28). The BBB opening pressure threshold was identified by varying
      the peak-rarefactional pressure amplitude. BBB opening was determined by
      fluorescence enhancement due to systemically administered, fluorescent-tagged, 3
      kDa dextran. The identified threshold fell between 0.30 and 0.46 MPa in the case
      of 1-2 microm bubbles and between 0.15 and 0.30 MPa in the 4-5 microm case. At
      every pressure studied, the fluorescence was greater with the 4-5 mum than with
      the 1-2 microm bubbles. At 0.61 MPa, in the 1-2 microm bubble case, the
      fluorescence amount and area were greater in the thalamus than in the
      hippocampus. In conclusion, it was determined that the FUS-induced BBB opening
      was dependent on both the size distribution in the injected microbubble volume
      and the brain region targeted.

PMID- 19846366
TI  - Detection of quality visualization of appendiceal orifices using local edge cross
      section profile features and near pause detection.
AB  - Colonoscopy is an endoscopic technique that allows a physician to inspect the
      inside of the human colon. The appearance of the appendiceal orifice during
      colonoscopy indicates a complete traversal of the colon, which is an important
      quality indicator of the colon examination. In this paper, we present two new
      algorithms. The first algorithm determines whether an image shows the clearly
      seen appendiceal orifice. This algorithm uses our new local features based on
      geometric shape, illumination difference, and intensity changes along the norm
      direction (cross section) of an edge. The second algorithm determines whether the
      video is an appendix video (the video showing at least 3 s of the appendiceal
      orifice inspection). Such a video indicates good visualization of the appendiceal
      orifice. This algorithm utilizes frame intensity histograms to detect a near
      camera pause during the apendiceal orifice inspection. We tested our algorithms
      on 23 videos captured from two types of endoscopy procedures. The average
      sensitivity and specificity for the detection of appendiceal orifice images with
      the often seen crescent appendiceal orifice shape are 96.86% and 90.47%,
      respectively. The average accuracy for the detection of appendix videos is
      91.30%.

PMID- 19846367
TI  - Analysis and modeling of snore source flow with its preliminary application to
      synthetic snore generation.
AB  - With the emerging use of snore properties for clinical purposes, there is a need
      to understand the characteristics of snore source flow (SF)-the acoustic source
      in snore production. This paper attempts to analyze and model both SF and its
      derivative (SFD), along with its preliminary application to the generation of
      synthetic snores. SFs and SFDs were extracted from natural snores via an
      iterative adaptive inverse filtering approach, and subsequently parameterized
      into various time- and amplitude-based parameters to quantify the oscillatory
      maneuvers of snore excitation source (ES). The SF and SFD waveforms were also,
      respectively, modeled using the first and second derivatives of the Gaussian
      probability density function. Subjective and objective measures, including paired
      comparison score and sum-of-squared error, were assessed to appraise the
      performance of SFD model in producing natural-sounding snores. Results
      consistently show that: 1) the shapes of SF pulse are different among snores and
      can be associated with the dynamic biomechanical properties (e.g., compliance and
      elasticity) of ES; 2) changes to the SF or SFD pulse shape can affect the snore
      properties, both acoustically and perceptually; and 3) the proposed SFD model can
      generate close-to-natural sounding snores. Further research in this area can
      potentially yield valuable benefits to snore-oriented applications.

PMID- 19846368
TI  - Across-frequency delays based on the cochlear traveling wave: enhanced speech
      presentation for cochlear implants.
AB  - Cochlear implants stimulate the auditory nerve with the outputs of a bank of
      narrow-band filters. We propose that cochlear implant users are better able to
      perceive speech when these frequency bands are desynchronized, as occurs in the
      normal cochlea. The first part of this study was a computational investigation of
      across-frequency delays on the stimulation patterns generated by the advanced
      combination encoder (ACE) sound-processing strategy. By offsetting frequency
      bands from each other, fewer stimuli were discarded from voiced speech by maxima
      selection. Background noise, however, was not affected in this way. The second
      part of this study was an assessment of speech perception with across-frequency
      delays in cochlear implant users with the ACE strategy. In the perception of
      sentences in noise, three subjects improved with delays, four showed no change
      and one was worse. For words in quiet, four subjects had improved word
      recognition and four showed no change. A significant group improvement ( P < 0.05
      ) was seen for speech in quiet. These results are encouraging for cochlear
      implant sound processing because across-frequency delays can be incorporated
      easily and efficiently into existing sound-processing strategies.

PMID- 19846369
TI  - Color graphs for automated cancer diagnosis and grading.
AB  - This paper reports a new structural method to mathematically represent and
      quantify a tissue for the purpose of automated and objective cancer diagnosis and
      grading. Unlike the previous structural methods, which quantify a tissue
      considering the spatial distributions of its cell nuclei, the proposed method
      relies on the use of distributions of multiple tissue components for the
      representation. To this end, it constructs a graph on multiple tissue components
      and colors its edges depending on the component types of their endpoints.
      Subsequently, it extracts a new set of structural features from these color
      graphs and uses these features in the classification of tissues. Working with the
      images of colon tissues, our experiments demonstrate that the color-graph
      approach leads to 82.65% test accuracy and that it significantly improves the
      performance of its counterparts.

PMID- 19846370
TI  - Bayesian approach to patient-tailored vectorcardiography.
AB  - For assessment of specific cardiac pathologies, vectorcardiography is generally
      considered superior with respect to electrocardiography. Existing
      vectorcardiography methods operate by calculating the vectorcardiogram (VCG) as a
      fixed linear combination of ECG signals. These methods, with the inverse Dower
      matrix method the current standard, are therefore not flexible with respect to
      different body compositions and geometries. Hence, they cannot be applied with
      accuracy on patients that do not conform to the fixed standard. Typical examples
      of such patients are obese patients or fetuses. For the latter category, when
      recording the fetal ECG from the maternal abdomen the distance of the fetal heart
      with respect to the electrodes is unknown. Consequently, also the signal
      attenuation/transformation per electrode is not known. In this paper, a Bayesian
      method is developed that estimates the VCG and, to some extent, also the signal
      attenuation in multichannel ECG recordings from either the adult 12-lead ECG or
      the maternal abdomen. This is done by determining for which VCG and signal
      attenuation the joint probability over both these variables is maximal given the
      observed ECG signals. The underlying joint probability distribution is determined
      by assuming the ECG signals to originate from scaled VCG projections and additive
      noise. With this method, a VCG, tailored to each specific patient, is determined.
      The method is compared to the inverse Dower matrix method by applying both
      methods on standard 12-lead ECG recordings and evaluating the performance in
      predicting ECG signals from the determined VCG. In addition, to model nonstandard
      patients, the 12-lead ECG signals are randomly scaled and, once more, the
      performance in predicting ECG signals from the VCG is compared between both
      methods. Finally, both methods are also compared on fetal ECG signals that are
      obtained from the maternal abdomen. For patients conforming to the standard, both
      methods perform similarly, with the developed method performing marginally
      better. For scaled ECG signals and fetal ECG signals, the developed method
      significantly outperforms the inverse Dower matrix method.

PMID- 19846371
TI  - A gain-scheduling model predictive controller for blood glucose control in type 1
      diabetes.
AB  - This paper presents a control strategy for blood glucose (BG) level regulation in
      type 1 diabetic patients. To design the controller, model-based predictive
      control scheme has been applied to a newly developed diabetic patient model. The
      controller is provided with a feedforward loop to improve meal compensation, a
      gain-scheduling scheme to account for different BG levels, and an asymmetric cost
      function to reduce hypoglycemic risk. A simulation environment that has been
      approved for testing of artificial pancreas control algorithms has been used to
      test the controller. The simulation results show a good controller performance in
      fasting conditions and meal disturbance rejection, and robustness against model
      patient mismatch and errors in meal estimation.

PMID- 19846372
TI  - Learning nonsparse kernels by self-organizing maps for structured data.
AB  - The development of neural network (NN) models able to encode structured input,
      and the more recent definition of kernels for structures, makes it possible to
      directly apply machine learning approaches to generic structured data. However,
      the effectiveness of a kernel can depend on its sparsity with respect to a
      specific data set. In fact, the accuracy of a kernel method typically reduces as
      the kernel sparsity increases. The sparsity problem is particularly common in
      structured domains involving discrete variables which may take on many different
      values. In this paper, we explore this issue on two well-known kernels for trees,
      and propose to face it by recurring to self-organizing maps (SOMs) for
      structures. Specifically, we show that a suitable combination of the two
      approaches, obtained by defining a new class of kernels based on the activation
      map of a SOM for structures, can be effective in avoiding the sparsity problem
      and results in a system that can be significantly more accurate for
      categorization tasks on structured data. The effectiveness of the proposed
      approach is demonstrated experimentally on two relatively large corpora of XML
      formatted data and a data set of user sessions extracted from website logs.

PMID- 19846373
TI  - Efficient stereoscopic ranging via stochastic sampling of match quality.
AB  - We present an efficient method that computes dense stereo correspondences by
      stochastically sampling match quality values. Nonexhaustive sampling facilitates
      the use of quality metrics that take unique values at noninteger disparities.
      Depth estimates are iteratively refined with a stochastic cooperative search by
      perturbing the estimates, sampling match quality, and reweighting and aggregating
      the perturbations. The approach gains significant efficiencies when applied to
      video, where initial estimates are seeded using information from the previous
      pair in a novel application of the Z-buffering algorithm. This significantly
      reduces the number of search iterations required. We present a quantitative
      accuracy evaluation wherein the proposed method outperforms a microcanonical
      annealing approach by Barnard and a cooperative approach by Zitnick and Kanade ,
      while using fewer match quality evaluations than either. The approach is shown to
      have more attractive memory usage and scaling than alternatives based on
      exhaustive sampling.

PMID- 19846374
TI  - Motion tuned spatio-temporal quality assessment of natural videos.
AB  - There has recently been a great deal of interest in the development of algorithms
      that objectively measure the integrity of video signals. Since video signals are
      being delivered to human end users in an increasingly wide array of applications
      and products, it is important that automatic methods of video quality assessment
      (VQA) be available that can assist in controlling the quality of video being
      delivered to this critical audience. Naturally, the quality of motion
      representation in videos plays an important role in the perception of video
      quality, yet existing VQA algorithms make little direct use of motion
      information, thus limiting their effectiveness. We seek to ameliorate this by
      developing a general, spatio-spectrally localized multiscale framework for
      evaluating dynamic video fidelity that integrates both spatial and temporal (and
      spatio-temporal) aspects of distortion assessment. Video quality is evaluated not
      only in space and time, but also in space-time, by evaluating motion quality
      along computed motion trajectories. Using this framework, we develop a full
      reference VQA algorithm for which we coin the term the MOtion-based Video
      Integrity Evaluation index, or MOVIE index. It is found that the MOVIE index
      delivers VQA scores that correlate quite closely with human subjective judgment,
      using the Video Quality Expert Group (VQEG) FRTV Phase 1 database as a test bed.
      Indeed, the MOVIE index is found to be quite competitive with, and even
      outperform, algorithms developed and submitted to the VQEG FRTV Phase 1 study, as
      well as more recent VQA algorithms tested on this database.

PMID- 19846375
TI  - A method for compact image representation using sparse matrix and tensor
      projections onto exemplar orthonormal bases.
AB  - We present a new method for compact representation of large image datasets. Our
      method is based on treating small patches from a 2-D image as matrices as opposed
      to the conventional vectorial representation, and encoding these patches as
      sparse projections onto a set of exemplar orthonormal bases, which are learned a
      priori from a training set. The end result is a low-error, highly compact
      image/patch representation that has significant theoretical merits and compares
      favorably with existing techniques (including JPEG) on experiments involving the
      compression of ORL and Yale face databases, as well as a database of
      miscellaneous natural images. In the context of learning multiple orthonormal
      bases, we show the easy tunability of our method to efficiently represent patches
      of different complexities. Furthermore, we show that our method is extensible in
      a theoretically sound manner to higher-order matrices ("tensors"). We demonstrate
      applications of this theory to compression of well-known color image datasets
      such as the GaTech and CMU-PIE face databases and show performance competitive
      with JPEG. Lastly, we also analyze the effect of image noise on the performance
      of our compression schemes.

PMID- 19846376
TI  - Credal semantics of bayesian transformations in terms of probability intervals.
AB  - In this paper, we propose a credal representation of the interval probability
      associated with a belief function (b.f.) and show how it relates to several
      classical Bayesian transformations of b.f.'s through the notion of ?focus? of a
      pair of simplices. While a b.f. corresponds to a polytope of probabilities
      consistent with it, the related interval probability is geometrically represented
      by a pair of upper and lower simplices. Starting from the interpretation of the
      pignistic function as the center of mass of the credal set of consistent
      probabilities, we prove that the relative belief of singletons, the relative
      plausibility of singletons, and the intersection probability can all be described
      as the foci of different pairs of simplices in the region of all probability
      measures. The formulation of frameworks similar to the transferable belief model
      for such Bayesian transformations appears then at hand.

PMID- 19846377
TI  - Efficient sensor selection for active information fusion.
AB  - In our previous paper, we formalized an active information fusion framework based
      on dynamic Bayesian networks to provide active information fusion. This paper
      focuses on a central issue of active information fusion, i.e., the efficient
      identification of a subset of sensors that are most decision relevant and cost
      effective. Determining the most informative and cost-effective sensors requires
      an evaluation of all the possible subsets of sensors, which is computationally
      intractable, particularly when information-theoretic criterion such as mutual
      information is used. To overcome this challenge, we propose a new quantitative
      measure for sensor synergy based on which a sensor synergy graph is constructed.
      Using the sensor synergy graph, we first introduce an alternative measure to
      multisensor mutual information for characterizing the sensor information gain. We
      then propose an approximated nonmyopic sensor selection method that can
      efficiently and near-optimally select a subset of sensors for active fusion. The
      simulation study demonstrates both the performance and the efficiency of the
      proposed sensor selection method.

PMID- 19846378
TI  - Nonconstrained sleep monitoring system and algorithms using air-mattress with
      balancing tube method.
AB  - We evaluated the performance of a bed-type sensor system using the air-mattress
      with balancing tube (AMBT) method to noninvasively monitor the signals of
      heartbeat, respiration, and events of snoring, sleep apnea and body movement of
      subject on the system. The proposed system consists of multiple cylindrical air
      cells, two sensor cells and 18 support cells, and the small physiological signals
      were measured by the changes in pressure difference between the sensor cells, and
      the dc component was removed by balancing tube that is connecting the sensor
      cells. Using newly developed AMBT method, heartbeat, respiration, snoring, and
      body movement signals were clearly measured. For the concept of a home healthcare
      system, two automatic processing algorithms were developed: one is to estimate
      the mean heart and respiration rates for every 30 s, and another one is to detect
      the snoring, sleep apnea, and body movement events from the measured signals. In
      the beat-to-beat heart rate and breath-by-breath respiration rate analyses, the
      correlation coefficients of the heart and respiration rates from the proposed
      AMBT method compared with reference methods, electrocardiogram, and respiration
      effort signal from piezoelectric belt, were 0.98 ( p << 0.01) and 0.96 ( p <<
      0.01), respectively. Sensitivity and positive predictive value (PPV) of the
      detection algorithm for snoring event were 93%, 96%, for sleep apnea event were
      93%, 88%, and for body movement event were 86%, 100%, respectively. These
      findings support that ABMT method provides an accurate and reliable means to
      monitor heartbeat, respiration activities and the sleep events during sleep.

PMID- 19846379
TI  - A wearable airbag to prevent fall injuries.
AB  - We have developed a wearable airbag that incorporates a fall-detection system
      that uses both acceleration and angular velocity signals to trigger inflation of
      the airbag. The fall-detection algorithm was devised using a thresholding
      technique with an accelerometer and gyro sensor. Sixteen subjects mimicked falls,
      and their acceleration waveforms were monitored. Then, we developed a fall
      detection algorithm that could detect signals 300 ms before the fall. This signal
      was used as a trigger to inflate the airbag to a capacity of 2.4 L. Although the
      proposed system can help to prevent fall-related injuries, further development is
      needed to miniaturize the inflation system.

PMID- 19846380
TI  - Energy-efficient low duty cycle MAC protocol for wireless body area networks.
AB  - This paper presents an energy-efficient medium access control protocol suitable
      for communication in a wireless body area network for remote monitoring of
      physiological signals such as EEG and ECG. The protocol takes advantage of the
      static nature of the body area network to implement the effective time-division
      multiple access (TDMA) strategy with very little amount of overhead and almost no
      idle listening (by static, we refer to the fixed topology of the network
      investigated). The main goal is to develop energy-efficient and reliable
      communication protocol to support streaming of large amount of data. TDMA
      synchronization problems are discussed and solutions are presented. Equations for
      duty cycle calculation are also derived for power consumption and battery life
      predictions. The power consumption model was also validated through measurements.
      Our results show that the protocol is energy efficient for streaming
      communication as well as sending short bursts of data, and thus can be used for
      different types of physiological signals with different sample rates. The
      protocol is implemented on the analog devices ADF7020 RF transceivers.

PMID- 19846381
TI  - Data mining of gene expression data by fuzzy and hybrid fuzzy methods.
AB  - Microarray studies and gene expression analysis have received tremendous
      attention over the last few years and provide many promising avenues toward the
      understanding of fundamental questions in biology and medicine. Data mining of
      these vasts amount of data is crucial in gaining this understanding. In this
      paper, we present a fuzzy rule-based classification system that allows for
      effective analysis of gene expression data. The applied classifier consists of a
      set of fuzzy if-then rules that enable accurate nonlinear classification of input
      patterns. We further present a hybrid fuzzy classification scheme in which a
      small number of fuzzy if-then rules are selected through means of a genetic
      algorithm, leading to a compact classifier for gene expression analysis.
      Extensive experimental results on various well-known gene expression datasets
      confirm the efficacy of our approaches.

PMID- 19846382
TI  - Monitoring motor fluctuations in patients with Parkinson's disease using wearable
      sensors.
AB  - This paper presents the results of a pilot study to assess the feasibility of
      using accelerometer data to estimate the severity of symptoms and motor
      complications in patients with Parkinson's disease. A support vector machine
      (SVM) classifier was implemented to estimate the severity of tremor, bradykinesia
      and dyskinesia from accelerometer data features. SVM-based estimates were
      compared with clinical scores derived via visual inspection of video recordings
      taken while patients performed a series of standardized motor tasks. The analysis
      of the video recordings was performed by clinicians trained in the use of scales
      for the assessment of the severity of Parkinsonian symptoms and motor
      complications. Results derived from the accelerometer time series were analyzed
      to assess the effect on the estimation of clinical scores of the duration of the
      window utilized to derive segments (to eventually compute data features) from the
      accelerometer data, the use of different SVM kernels and misclassification cost
      values, and the use of data features derived from different motor tasks. Results
      were also analyzed to assess which combinations of data features carried enough
      information to reliably assess the severity of symptoms and motor complications.
      Combinations of data features were compared taking into consideration the
      computational cost associated with estimating each data feature on the nodes of a
      body sensor network and the effect of using such data features on the reliability
      of SVM-based estimates of the severity of Parkinsonian symptoms and motor
      complications.

PMID- 19846383
TI  - Understanding and supporting lightweight communication in hospital work.
AB  - Informal communication is an essential resource in hospital work; it is used as a
      means to collaborate and coordinate the way in which work is performed, as well
      as to locate and gather the artifacts and human resources required for patient
      care. The need of physical proximity to establish and hold informal
      communications has motivated the development of tools that support remote
      informal interaction. However, this kind of technology has not been widely
      adopted in hospitals, where workers experience intense mobility. In this paper,
      we present the results of an observational study in a hospital aimed at
      understanding how local mobility changes the rules in the provision of support
      for informal communication, and how technology could improve this form of
      communication. We found that local mobility fosters opportunities for colocated
      communication; however, it faces some inconveniences related to the affordances
      of the physical environment. We address these issues through the design of SOLAR,
      a collaborative application that supports colocated interactions in hospital work
      through the implementation and integration of five services that form a ubicomp
      infrastructure. Additionally, we present a discussion about the perception of
      users related to the usefulness of this tool.

PMID- 19846384
TI  - Segmentation of regions of interest in mammograms in a topographic approach.
AB  - This paper presents a novel method for the segmentation of regions of interest in
      mammograms. The algorithm concurrently delineates the boundaries of the breast
      boundary, the pectoral muscle, as well as dense regions that include candidate
      masses. The resulting representation constitutes an analysis of the global
      structure of the object in the mammogram. We propose a topographic representation
      called the isocontour map, in which a salient region forms a dense quasi
      concentric pattern of contours. The topological and geometrical structure of the
      image is analyzed using an inclusion tree that is a hierarchical representation
      of the enclosure relationships between contours. The "saliency" of a region is
      measured topologically as the minimum nesting depth. Features at various scales
      are analyzed in multiscale isocontour maps, and we demonstrate that the
      multiscale scheme provides an efficient way of achieving better delineations.
      Experimental results demonstrate that the proposed method has potential as the
      basis for a prompting system in mammogram mass detection.

PMID- 19846385
TI  - In-ear vital signs monitoring using a novel microoptic reflective sensor.
AB  - Cardiovascular diseases are among the most common causes of death in industrial
      countries. In order to take preventive actions, it is of great interest, to both
      physicians and patients, to determine cardiovascular risk factors early. To
      address this problem, a wearable in-ear measuring system (IN-MONIT) for 24/7
      monitoring of vital parameters has been developed. The central component is a
      microoptic reflective sensor located inside the auditory canal. From the measured
      photoplethysmographic curves, heart activity and heart rate can be derived. In
      this paper, we describe the optoelectronic sensor concept and the autonomous
      design of the IN-MONIT measurement system. For the assessment of heart rate,
      different algorithms are introduced and the performance of the developed sensor
      system is evaluated in relation to conventional systems. In addition, the
      robustness to external artifacts is evaluated and artifact reduction strategies
      are considered.

PMID- 19846386
TI  - Universal haptic drive: a robot for arm and wrist rehabilitation.
AB  - In this paper we present a universal haptic drive (UHD), a device that enables
      rehabilitation of either arm ("ARM" mode) or wrist ("WRIST" mode) movement in two
      degrees-of-freedom. The mode of training depends on the selected mechanical
      configuration, which depends on locking/unlocking of a passive universal joint.
      Actuation of the device is accomplished by utilizing a series elastic actuation
      principle, which enables use of off-the-shelf mechanical and actuation
      components. A proportional force control scheme, needed for implementation of
      impedance control based movement training, was implemented. The device
      performance in terms of achievable lower and upper bound of viable impedance
      range was evaluated through adequately chosen sinusoidal movement in eight
      directions of a planar movement for the "ARM" mode and in eight directions of a
      combined wrist flexion/extension and forearm pronation/supination movement for
      the "WRIST" mode. Additionally, suitability of the universal haptic drive for
      movement training was tested in a series of training sessions conducted with a
      chronic stroke subject. The results have shown that reliable and repeatable
      performance can be achieved in both modes of operation for all tested directions.

PMID- 19846387
TI  - [Radiological digital imaging: a new tool for the patient medical file].
AB  - This paper will focus on the positive vs negative in-puts of new radiological
      imaging in the patient medical file.

PMID- 19846388
TI  - Increased jump height with an external focus due to enhanced lower extremity
      joint kinetics.
AB  - Individuals jump higher when they adopt an external focus of attention, relative
      to an internal focus or no focus of attention (G. Wulf, T. Zachry, C. Granados, &
      J. S. Dufek, 2007). In the present study, the authors determined the underlying
      cause of this effect. Participants performed a vertical jump-and-reach task for
      (a) an external focus condition (i.e., participants focused on the rungs of a
      Vertec [Perform Better, Cranston, RI] measurement device that they touched) and
      (b) an internal focus condition (i.e., participants focused on the finger with
      which they touched the rungs). Participants' jump height, center-of-mass
      displacement, jump impulse, and lower extremity joint moments were greater with
      an external focus compared with an internal focus. These results suggest that
      participants jump higher by producing greater forces when they adopt an external
      focus. This finding adds to evidence that an external focus facilitates the
      production of effective and efficient movement patterns.

PMID- 19846389
TI  - Changes in neurodevelopmental outcome at age eight in geographic cohorts of
      children born at 22-27 weeks' gestational age during the 1990s.
AB  - BACKGROUND: The survival rate for children born with gestational ages 22-27 weeks
      is increasing, and this may be associated with higher rates of disability. The
      aims of this study were to determine the outcomes at age eight for a regional
      cohort of children born at 22-27 weeks during 1997, and to compare their rates of
      disability with a cohort of the same gestational age born in 1991-1992. METHODS:
      Consecutive children with gestational ages in the range 22-27 weeks born in the
      state of Victoria, Australia, in 1997 and matched term controls were assessed at
      8 years. Outcomes included blindness, deafness, cerebral palsy (CP) and
      intellectual impairment and disabilities caused by these impairments. These
      outcomes were compared with a cohort of 22-27-week and term children born in 1991
      1992 in the same region. RESULTS: Follow-up rates for the 1997 cohort at 8 years
      of age were 95% (144/151) for 22-27 weeks survivors and 89% (173/195) for
      controls. Rates of disability were substantially higher in the preterm cohort
      than the controls. The 1997 and 1991-1992 preterm cohorts had similar rates of
      moderate or severe disability (19%), however the rate of mild impairment was
      greater in 1997 (40% vs 24%). Rates of disability were almost identical in
      control groups. Intellectual impairment and CP were the major reasons for the
      higher rates of disability. CONCLUSIONS: The high prevalence of adverse
      neurodevelopmental outcome in children born at 22-27 weeks compared with term
      controls at school age persists, and may even be increasing over time.

PMID- 19846390
TI  - Results of surgical treatment for renovascular hypertension in children: 30 year
      single centre experience.
AB  - BACKGROUND: We retrospectively reviewed the medical records of all patients who
      underwent surgery as part of the treatment of renovascular hypertension (RVH) at
      our centre between 1979 and 2008. Patients. Thirty-seven children (65% male) with
      a median age of 7.6 (0.4-17.9) years were identified with a median systolic blood
      pressure (SBP) of 140 (105-300) mm Hg prior to surgery. Bilateral renal artery
      stenosis and intra-renal disease were present in 19 (51%) patients, mid-aortic
      syndrome in 15 (40%), involvement of visceral arteries in eight out of 35 (23%)
      and coexisting cerebral disease in eight out of 30 (26%) investigated patients.
      RESULTS: Surgical procedures (n = 53) included (i) nephrectomy (18, of which two
      unplanned and two secondary due to technical failure), (ii) renovascular surgery
      on the renal arteries (28, of which 18 had autologous surgery and 10 synthetic
      grafts inserted for revascularisation) and (iii) aortic reconstruction with (6)
      and without (1) a synthetic graft. Post-operative complications were haemorrhage
      (5), septicaemia (5) and chylous ascites (1). There were no perioperative deaths;
      two children died during follow-up. The SBP post-surgery improved to a median
      value of 116 (range 90-160) mm Hg. Twelve months after surgery, 16 (43%) children
      had normal blood pressure without treatment, 15 (41%) normal or improved on one
      to four antihypertensive drugs and four (11%) unchanged; no data were available
      for two (5%) children. CONCLUSION: Surgery effectively treated the hypertension
      of 90% of our children, when performed in conjunction with medical therapy and
      interventional radiology. In spite of aggressive surgical treatment, RVH is
      sometimes a progressive disease.

PMID- 19846391
TI  - Improved survival of type 2 diabetic patients on renal replacement therapy in
      Finland.
AB  - BACKGROUND: Survival of type 2 diabetes mellitus patients on maintenance dialysis
      therapy is poor mainly due to cardiovascular events. The aim was to examine
      whether survival of type 2 diabetes patients on renal replacement therapy (RRT)
      in Finland has improved during 1995-2005. METHODS: Patients who entered RRT
      because of type 2 diabetes mellitus in 1995-99 (n = 314) and 2000-05 (n = 583)
      were identified within the Finnish Registry for Kidney Diseases. The two cohorts
      were followed up from start of RRT until death or end of follow-up on 31 December
      2006. Survival probabilities and probabilities of receiving a kidney transplant
      were calculated using Kaplan-Meier curves. Multivariate modelling was performed
      using Cox regression. RESULTS: Patients who entered RRT in 2000-05 had lower risk
      of dying than those who entered in 1995-99; hazard ratio (HR) was 0.76 (95% CI
      0.65-0.89) and 0.74 (95% CI 0.63-0.87) with adjustment for age and gender. The
      decreased risk of death was most obvious in age groups 55-64 (HR 0.67, 95% CI
      0.49-0.92) and 65-74 years (HR 0.69, 95% CI 0.56-0.87). Adjustment for albumin in
      addition to age and gender only slightly weakened the effect of study periods (HR
      0.83, 95% CI 0.69-1.01). The patients in 2000-05 were more obese, had lower total
      and LDL cholesterol and higher HDL cholesterol and albumin concentration in serum
      than patients in 1995-99. Patients' probability to receive a kidney transplant
      was low in both groups. CONCLUSIONS: Survival of type 2 diabetes patients on RRT
      improved during the time period 1995-2005 in Finland while the probability of
      receiving a kidney transplant remained low and unchanged.

PMID- 19846392
TI  - Influenza A(H1N1)v pandemic in the dialysis population: first wave results from
      an international survey.
AB  - BACKGROUND: After the first cases of influenza A(H1N1)v in Mexico and the USA
      became public, Fresenius Medical Care established a case-based reporting of cases
      for all of its dialysis clinics located in Europe, Middle East, Africa and Latin
      America. This paper aims to describe mortality rates of patients on dialysis and
      to assess the risk profiles. METHODS: The survey was developed in Lotus Notes
      with a secure browser-based form. The form was open to 602 Fresenius Medical Care
      clinics located in Europe, Middle East, Africa and Latin America. RESULTS: As of
      3 September 2009, 306 cases have been reported by 85 clinics located in
      Argentina, Chile, Brazil, UK and Spain. The mean age was 52.7 +/- 17.7 years. The
      majority of cases (70.6%) were from 20- to 44-year-old and 45- to 64-year-old
      subgroups. Moreover, 35.3% had no associated comorbidity, 20.3% had two and 4.6%
      three comorbidities, with heart disease being the most frequent. Fever was the
      most common symptom, present in 94.4% of the cases, followed by cough (78.8%) and
      muscle and joint pain (69.3%). Eighty-seven percent were treated with antiviral
      agents, the majority with oseltamivir. One hundred and three patients (34%) were
      admitted to hospital because of influenza. Pneumonia was reported for 69 cases,
      out of which 52 patients belonged to a high-risk group. Mortality rate of all the
      patients (confirmed, probable and suspected cases) was around 5%. CONCLUSION: End
      stage renal disease patients should be included in first ranks of the priority
      list for the influenza A (H1N1)v vaccine, as already advocated by some healthcare
      authorities.

PMID- 19846393
TI  - Pre-diabetes and arterial stiffness in uraemic patients.
AB  - BACKGROUND: In order to address factors of relevance for new onset diabetes
      mellitus and cardiovascular disease after kidney transplantation, we investigated
      the presence of pre-diabetes, arterial stiffness and endothelial dysfunction in
      patients with end-stage renal disease (ESRD) accepted for kidney transplantation.
      METHODS: Pre-diabetes and an insulin sensitivity index were estimated by an oral
      glucose tolerance test in 66 consecutive uraemic patients, without diabetes,
      being on the waiting list for the first renal transplantation. Mean age was 43 +/
      13 years. Duration of ESRD was 32 +/- 27 months. A control group consisted of 14
      healthy subjects. Arterial stiffness was measured by aorta pulse wave velocity
      (PWV) and aorta augmentation index (AIX). Endothelial function was evaluated by
      flow-mediated vasodilatation (FMD) and plasma concentrations of von Willebrand
      factor antigen (vWF). Mean arterial blood pressure (MAP) was measured in supine
      resting position. RESULTS: Twenty-seven uraemic patients (41%) had pre-diabetes
      (IFG+IGT), and 39 had normal glucose tolerance. The uraemic patients were more
      insulin resistant with lower insulin sensitivity index compared to healthy
      controls (6.1 +/- 3 vs. 15 +/- 7, P < 0.0001) but with no difference between
      patients with and without pre-diabetes. HbA1c and fasting plasma glucose was
      comparable in uraemic patients with and without pre-diabetes. PWV was higher in
      pre-diabetic compared to normoglycaemic uraemic patients (9.1 +/- 3 vs. 7.3 +/- 2
      m/s, P = 0.03) and healthy controls (9.1 +/- 3 vs. 6.7 +/- 1, P = 0.01), while
      AIX did not differ (24.9 +/- 13 vs. 23.2 +/- 12 vs. 17 +/- 16, P = NS). Presence
      of pre-diabetes was positively associated to PWV in a univariate analysis.
      Multivariable analysis revealed age and MAP as independent predictors of PWV in
      uraemic patients. FMD and vWF were impaired in uraemic patients compared to
      healthy controls (3 +/- 4 vs. 7 +/- 3, P = 0.007 and 1.8 +/- 0.7 vs. 0.96 +/- 0.3
      kIU/L, P = 0.0002, respectively) but with no difference between the two groups of
      uraemic patients. In conclusion, a high prevalence of pre-diabetes, impaired
      insulin resistance, increased arterial stiffness of aorta as well as impaired
      augmentation index and vasodilatation was demonstrated in uraemic patients prior
      to kidney transplantation. Increased arterial stiffness of aorta and augmentation
      index were independently associated with age and blood pressure.

PMID- 19846394
TI  - End-stage renal disease in patients with Fabry disease: natural history data from
      the Fabry Registry.
AB  - BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder caused by
      deficiency of alpha-galactosidase activity, is associated with progressive loss
      of kidney function. This study was undertaken to characterize Fabry disease among
      patients who reached end-stage renal disease. METHODS: Data from 2,712 patients
      in the Fabry Registry were analysed to identify clinical characteristics of
      patients who received renal replacement therapy (RRT) during the natural history
      period (i.e. prior to any enzyme replacement therapy). RESULTS: A total of 213
      patients [186 of 1,359 males (14%) and 27 of 1,353 females (2%)] received RRT at
      a median age of 38 years in both males and females. Males who received RRT were
      diagnosed at a median age of 35 years, compared to 23 years for non-RRT males.
      Sixty-one males and 10 females were not diagnosed with Fabry disease until after
      they had received RRT. Compared to other Fabry Registry patients, a higher
      percentage of RRT patients also experienced either a serious cardiovascular event
      or a stroke. Ninety-two of 186 males who had RRT (50%) experienced a cardiac
      event or stroke, compared to 230 of 1,173 non-RRT males (20%). Ten of 27 RRT
      females (37%) had experienced a cardiac event or stroke, compared to 226 of 1,326
      non-RRT females (17%). Patients who had RRT experienced cardiovascular events and
      strokes at earlier ages than did patients who had not received RRT, and most
      received RRT before having a cardiac event or stroke. CONCLUSIONS: While all
      Fabry patients are at risk of cardiovascular events and strokes, patients with
      Fabry nephropathy who develop kidney failure appear to have concurrent
      involvement of other major organ systems. It is important that Fabry patients are
      diagnosed early and that their renal function is monitored carefully.

PMID- 19846395
TI  - Renal phenotype of the cystinosis mouse model is dependent upon genetic
      background.
AB  - BACKGROUND: Cystinosis is caused by mutations in CTNS that encodes cystinosin,
      the lysosomal cystine transporter. The most severe and frequent form is
      characterized by a proximal tubulopathy that appears around 6 to 12 months of
      age. In the absence of treatment, end-stage renal disease is reached by 10 years.
      Ctns(-/-) mice of a mixed 129Sv x C57BL/6 genetic background show elevated renal
      cystine levels; however, proximal tubulopathy or end-stage renal disease is not
      observed. METHODS: As renal phenotype can be influenced by genetic background, we
      generated congenic C57BL/6 and FVB/N Ctns(-/-) mice and assayed renal lesions and
      function by histological and biochemical studies. RESULTS: C57BL/6 Ctns(-/-) mice
      showed significantly higher renal cystine levels than the FVB/N strain. Moreover,
      C57BL/6 mice presented with pronounced histological lesions of the proximal
      tubules as well as a tubulopathy and progressively developed chronic renal
      failure. In contrast, renal dysfunction was not observed in the FVB/N strain.
      CONCLUSIONS: Thus, the C57BL/6 strain represents the first Ctns(-/-) mouse model
      to show clear renal defects. In addition to highlighting the influence of genetic
      background on phenotype, the C57BL/6 Ctns(-/-) mice represent a useful model for
      further understanding cystinosin function in the kidney and, specifically, in the
      proximal tubules.

PMID- 19846397
TI  - Safety of "inert" additives or excipients in paediatric medicines.

PMID- 19846396
TI  - Antibody-mediated rejection following transplantation from an HLA-identical
      sibling.
AB  - Putative antibody-mediated rejection (AMR) in HLA-identical sibling
      transplantation has rarely been reported and occurred before routine calcineurin
      inhibitor use. A 29-year-old male developed allograft dysfunction following an
      HLA-identical renal transplant from his sibling. A pretransplant panel-reactive
      antibody (PRA) was elevated, pre-transplant crossmatch was negative and no donor
      specific antibody (DSA) was identified. Induction with alemtuzumab was followed
      by maintenance immunosuppression with corticosteroids, tacrolimus and
      mycophenolate. A biopsy for allograft dysfunction suggested AMR, but DSA could
      not be detected. Treatment for rejection was transiently successful. Undetectable
      minor histocompatibility antibodies may have contributed.

PMID- 19846398
TI  - Severe bilateral intracranial haemorrhage due to alloimmune thrombozytopenia in a
      premature infant.

PMID- 19846399
TI  - Potential hazards of the Neopuff: using appropriate gas flow.

PMID- 19846400
TI  - Incidence and treatment of severe retinopathy of prematurity.

PMID- 19846401
TI  - Sildenafil use in congenital diaphragmatic hernia.

PMID- 19846404
TI  - Nasal high-flow therapy delivers low level positive airway pressure.
AB  - BACKGROUND: The aim of this prospective study was to determine whether a level of
      positive airway pressure was generated in participants receiving nasal high flow
      (NHF) delivered by the Optiflow system (Fisher and Paykel Healthcare Ltd,
      Auckland, New Zealand) in a cardiothoracic and vascular intensive care unit
      (ICU). METHODS: Nasopharyngeal airway pressure was measured in 15 postoperative
      cardiac surgery adult patients who received both NHF and standard facemask
      therapy at a flow rate of 35 litre min(-1). Measurements were repeated in the
      open mouth and closed mouth positions. Mean airway pressure was determined by
      averaging the pressures at the peak of inspiration of each breath within a 1 min
      period, allowing the entire pressure profile of each breath to be included within
      the calculation. RESULTS: Low level positive pressure was demonstrated with NHF
      at 35 litre min(-1) with mouth closed when compared with a facemask. NHF
      generated a mean nasopharyngeal airway pressure of mean (SD) 2.7 (1.04) cm H(2)O
      with the mouth closed. Airway pressure was significantly higher when breathing
      with mouth closed compared with mouth open (P<or=0.0001). CONCLUSIONS: This study
      demonstrated that a low level of positive pressure was generated with NHF at 35
      litre min(-1) of gas flow. This is consistent with results obtained in healthy
      volunteers. Australian Clinical Trials Registry www.actr.org.au
      ACTRN012606000139572.

PMID- 19846406
TI  - Randomized crossover comparison between the i-gel and the LMA-Unique in
      anaesthetized, paralysed adults.
AB  - BACKGROUND: The i-gel differs from other supraglottic airway devices, in that it
      has a softer, non-inflatable cuff. This study was designed to compare the
      performance of the i-gel and the LMA-Unique (LMA-U) when used during anaesthesia
      in paralysed patients. METHODS: Both devices were studied in 39 anaesthetized,
      paralysed patients in a randomized crossover trial. The primary outcome was
      airway leak pressure. Secondary outcomes included time to insertion, the number
      of insertion and reposition attempts, leak volumes, and leak fractions. RESULTS:
      There was no significant difference between the airway leak pressures of the two
      devices [median (IQR) leak pressures 25 (22-30) vs 22 (20-28) cm H(2)O for the i
      gel and LMA-U, respectively; P=0.083, 95% CI of the mean difference -0.32 to 4.88
      cm H(2)O]. The median (IQR) insertion time for the i-gel was significantly less
      than for the LMA-U [12.2 (9.7-14.3) vs 15.2 (13.2-17.3) s; P=0.007]. All the LMA
      U devices and 38 of 39 i-gel airways were inserted at the first attempt. The
      number of manipulations required after insertion to achieve a clear airway was
      the same in both the groups (four in each). There were no statistically
      significant differences in leak volumes or leak fractions during controlled
      ventilation. CONCLUSIONS: We found no difference in leak pressures and success
      rate of first-time insertion between the i-gel and the LMA-U. Time to successful
      insertion was significantly shorter for the i-gel. We conclude that the i-gel
      provides a reasonable alternative to the LMA-U for controlled ventilation during
      anaesthesia.

PMID- 19846405
TI  - Recombinant activated factor VII for a patient with factor VII deficiency
      undergoing urgent intracerebral haematoma evacuation with underlying cavernous
      angioma.
AB  - Inherited factor VII (FVII) deficiency is a rare autosomal-recessive bleeding
      disorder. There are no clear guidelines regarding therapy in such patients when
      intracerebral surgery is performed. We report the use of recombinant activated
      FVII (rFVIIa) for the prophylaxis of bleeding in a female with FVII deficiency
      (8% of activity) undergoing urgent removal of a right fronto-rolandic
      intracerebral haematoma secondary to a bleeding from a cavernous angioma. To
      assist haemostasis during and after surgery, rFVIIa boluses were administered
      during the procedure and continued every 12 h during 3 days after operation to
      maintain a prothrombin time <15 s. Using this approach, no abnormal bleeding or
      thromboembolic complications were observed and rFVIIa appeared safe in this
      context.

PMID- 19846407
TI  - Repair of erosions occurs almost exclusively in damaged joints without swelling.
AB  - BACKGROUND: Negative radiographic change scores obtained under blinded time
      sequence conditions suggest that repair of joints may indeed occur. It is likely
      that, if repair truly exists, it would be preferentially seen in clinically
      inactive joints from patients treated with drugs with well-known structural
      efficacy. OBJECTIVE: To determine whether repair is associated with both the
      absence or improvement of swelling and with treatment. PATIENTS AND METHODS:
      Radiographs from patients of the TEMPO trial were scored twice by two readers
      according to the Sharp-van der Heijde score, blinded to both treatment and true
      time sequence. Single-joint change scores in erosions were coupled with single
      joint swelling scores obtained from clinical examination. Consistency of observed
      improvement across readers and repeat reads was described, and factors expected
      to increase the likelihood of occurrence of both worsening and improvement of
      erosion were tested by generalised estimating equations (GEE) modelling. RESULTS:
      In all of the four independent reads, the mean change in erosion score was
      statistically significantly negative only in the subgroup of joints with absent
      or improved swelling, when erosions were present at baseline. Multivariate
      analysis showed that worsening of the erosion score in a joint was significantly
      increased if that joint was already damaged at study entry, clinical swelling
      persisted and methotrexate was used instead of etanercept. Repair was associated
      with improvement of swelling and use of etanercept (p<or=0.007 for all
      associations). CONCLUSION: Repair of erosions almost exclusively occurs in joints
      with improvement or absence of swelling, in patients treated with etanercept.
      Progression is seen more frequently in joints with persistent swelling, in
      patients receiving methotrexate monotherapy, primarily if damage is already
      present.

PMID- 19846408
TI  - Anti-modified citrullinated vimentin (MCV) antibodies in patients with very early
      synovitis.

PMID- 19846409
TI  - The lymphatic system controls intestinal inflammation and inflammation-associated
      Colon Cancer through the chemokine decoy receptor D6.
AB  - BACKGROUND AND AIMS: Inflammatory CC chemokines have long been associated with
      cancer, but unequivocal evidence of a role in clinically relevant models of
      carcinogenesis is lacking. D6, a promiscuous decoy receptor that scavenges
      inflammatory CC chemokines, plays a non-redundant role in reducing the
      inflammatory response in various organs. As inflammation is a key player in the
      development of inflammatory bowel disease (IBD) and IBD-associated colorectal
      cancer, we investigated D6 expression in human colitis and colon cancer, and its
      role in experimental colitis and inflammation-associated colon cancer. RESULTS:
      In humans, D6 was mainly expressed by lymphatic vessels and leukocytes in the
      mucosa of individuals with IBD and colon cancer, as well as the mucosa of control
      individuals. Mice lacking expression of D6 were significantly more susceptible to
      experimental colitis than wild-type mice and failed to resolve colitis, with
      significantly higher levels of several pro-inflammatory chemokines. In bone
      marrow chimeric mice, the ability of D6 to regulate colitis was tracked to the
      stromal/lymphatic compartment, with no contribution of haemopoietic cells.
      Finally, after administration of the carcinogen azoxymethane, D6(-/-) mice showed
      increased susceptibility to colitis-associated cancer in the distal segment of
      the colon compared with wild-type mice. CONCLUSIONS: D6 expressed on lymphatic
      vessels plays a key role in the control of intestinal inflammation and the
      development of inflammation-associated colon cancer. Our results reveal a new
      unexpected role for the lymphatic system in the pathogenesis of IBD and
      intestinal cancer, and candidate chemokines as novel players in tumour promotion
      and progression.

PMID- 19846410
TI  - An interrater reliability study of a new 'zonal' classification for reporting the
      location of retinal haemorrhages in childhood for clinical, legal and research
      purposes.
AB  - BACKGROUND/AIMS: To develop and assess a zonal classification of the retina to
      facilitate description of the location of retinal haemorrhages in children.
      METHODS: A novel zonal classification of the retina was devised based on the
      anatomical landmarks of the optic disc and vascular arcades, by reviewing a large
      number of wide field digital retinal images drawn from our database of children
      with accidental and non-accidental head injury and other encepthalopathies. Four
      expert examiners then independently 'located' 142 retinal haemorrhages by zone,
      from 31 high quality photographs. RESULTS: Cohen's unweighted kappa scores for
      all possible pairs of the four raters (ie, six pairs) ranged from 0.86 to 0.92,
      that is 'almost perfect' agreement. Fleiss' kappa for agreement between multiple
      raters (four) and for multiple categories (three) was 0.8841, that is 'almost
      perfect' agreement. Cohen's unweighted kappa statistic for intrarater reliability
      gave an overall concordance that ranged from 'substantial' to 'perfect'
      agreement. CONCLUSION: This new retinal zone classification and the use of
      photographs and templates is a very reliable tool for reporting the location of
      retinal haemorrhages from multiple aetiologies in children, and may be useful for
      research and medico-legal reports.

PMID- 19846411
TI  - New observations concerning the nature of central retinal vein pulsation.
AB  - AIMS: Central retinal vein pulsation is affected by intracranial pressure (ICP),
      glaucoma and venous pathology. Its genesis is poorly understood with most models
      suggesting that intraocular pressure (IOP) fluctuation dominates the rhythm of
      venous pulsation; however, this has not been explored experimentally. This study
      planned to measure the timing of central retinal vein pulsation with respect to
      IOP pulse. METHODS: Video recording of the optic disc vessels and movement of
      Goldmann applanation mires while recording the cardiac cycle with a pulse
      oximeter probe was undertaken in 10 subjects from a general ophthalmic clinic.
      The timing of the variation in IOP and retinal vein diameter from the onset of
      the oximeter signal were expressed as a percentage of the cardiac cycle and also
      in degrees of the cycle. RESULTS: Minimum vein diameter occurred at a mean 40 ms
      (SD 47) after minimum IOP in 10 subjects with mean cardiac cycle length of 866 ms
      (SD 132), the delay representing 4% or 14 degrees (SD 5.1, 95% CI 0.3% to 8%) of
      the mean cardiac cycle. Maximum vein diameter occurred an average of 5 ms after
      maximum IOP (SD 57) representing 1% or 4 degrees (SD 6.9, 95% CI -4% to 6%) of
      the mean cardiac cycle. CONCLUSION: During venous pulsation, venous collapse
      occurred in time with ocular diastole and dilatation in time with systole. This
      is contrary to earlier conceptual understanding. The results suggest that the
      intracranial pulse pressure may be of equal importance to intraocular pulse
      pressure in producing venous pulsation.

PMID- 19846412
TI  - Indocyanine green angiography-guided laser photocoagulation combined with sub
      Tenon's capsule injection of triamcinolone acetonide for idiopathic macular
      telangiectasia.
AB  - AIMS Type 2 (perifoveal) telangiectasia often is refractory to treatment, because
      focal targets such as aneurysms are not detected by fluorescein angiography (FA)
      in these eyes. The authors evaluated the efficacy of indocyanine green
      angiography (IA)-guided laser photocoagulation and sub-Tenon's capsule injection
      of triamcinolone acetonide (STTA) for idiopathic macular telangiectasia. METHODS
      Seven eyes (seven patients; mean age, 72 years) were enrolled, five eyes with
      type 1 and two eyes with type 2. The mean follow-up was 10.6 months (range 7 to
      19). FA and IA were performed with the Heidelberg Retina Angiogram 2. Laser
      photocoagulation was applied to leaky vessels detected by late-phase IA
      (wavelength, 577 nm; power, 100-200 mW; spot size, 100-200 microm; and duration,
      0.2 s). STTA (20 mg) was injected after photocoagulation. The central macular
      thickness and macular volume were measured periodically by optical coherence
      tomography. The logarithm of the minimum angle of resolution (logMAR) visual
      acuity (VA) was measured. RESULTS IA identified leaky aneurysms or vessels. The
      final mean logMAR VA and the central macular thickness improved significantly
      from baseline (p=0.040, p=0.0002, respectively). The VA improved by 0.3 or more
      logMAR unit in two eyes (29%) and stabilised in five eyes (71%). No adverse
      effects were reported throughout follow-up. CONCLUSIONS IA can detect
      microangiopathy in eyes with idiopathic macular telangiectasia. IA-guided laser
      photocoagulation combined with STTA might be effective for treating types 1 and 2
      idiopathic macular telangiectasia. Further studies are needed to access the
      efficacy of IA-guided photocoagulation for treating type 2 telangiectasia.

PMID- 19846413
TI  - Air regurgitation in patients on continuous positive airway pressure (CPAP)
      therapy following dacrocystorhinostomy with or without Lester-Jones tube
      insertion.
AB  - AIM: To describe air regurgitation as a complication in patients on continuous
      positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA)
      following dacryocystorhinostomy (DCR) surgery with or without Lester-Jones tube
      (LJT) insertion. METHODS: A retrospective review of all patients with air
      regurgitation on CPAP therapy who previously underwent a DCR/LJT procedure.
      Patient demographics, lacrimal surgical history, CPAP therapy and outcome were
      recorded. RESULTS: Four male patients were identified. The mean age at
      presentation was 54 years. Two patients had an LJT inserted, and two patients had
      a DCR procedure, one was external, and one was endonasal. All four patients had
      resolution of their epiphora. Three patients had superficial epithelial
      keratopathy requiring lubricant therapy. All patients attempted using ointment to
      act as a barrier over the neo-ostium, which was unsuccessful. One patient had the
      LJT removed with resolution of the air regurgitation. Two patients changed their
      CPAP machines to variable, and three patients reduced the pressure of their CPAP
      therapy without any improvement. All three patients had persistence of air
      regurgitation at a mean follow-up of 18 months. CONCLUSIONS: Air regurgitation
      can occur following naso-lacrimal surgery in patients on CPAP therapy. Although
      this is an unusual complication, it should be discussed with the patient at the
      time of obtaining informed consent.

PMID- 19846414
TI  - Choroidal filling delay in choroidal neovascularisation due to pathological
      myopia.
AB  - AIM To assess the choroidal thickness and choroidal circulatory changes in eyes
      with myopic choroidal neovascularisation (mCNV). METHODS Retrospective,
      consecutive, observational case series. Forty-two consecutive eyes (17 eyes with
      newly diagnosed mCNV and 25 eyes without CNV) were included. Choroidal
      circulation was evaluated by indocyanine green angiography (ICGA), and choroidal
      thickness was measured by spectral-domain optical coherence tomography (SD-OCT).
      The factors associated with mCNV were evaluated. RESULTS Sixteen (94%) of 17 eyes
      with mCNV and six (24%) of 25 eyes without mCNV had well-defined hypofluorescence
      at the macular region on arterial phase ICGA, that is, a choroidal filling delay.
      Older age (p<0.001), the presence of a choroidal filling delay (p<0.001) and
      reduced choroidal thickness (p=0.003) were significantly associated with mCNV on
      univariate analysis. The most important of these three factors associated with
      mCNV, in order of importance, were the choroidal filling delay (OR=41.5, p<0.001)
      and choroidal thickness (per 1 microm, OR=0.97, p=0.01). Older age was
      significantly associated with both choroidal filling delay (per 1 year, OR=1.16,
      p<0.001) and choroidal thinning (regression coefficient=-1.22, p<0.001).
      CONCLUSIONS Significant choroidal changes were observed in eyes with mCNV.
      Ischaemia-induced growth factor expression caused by decreased choroidal
      perfusion may be related to the development of mCNV.

PMID- 19846415
TI  - Ocular firework trauma: a systematic review on incidence, severity, outcome and
      prevention.
AB  - AIM: To provide a systematic review on ocular firework trauma with emphasis on
      incidence and patient demographics, the extent of ocular trauma and visual
      function loss, and firework regulation effects on injury rates. METHODS: A
      literature search was performed using predetermined inclusion and exclusion
      criteria. Demographic characteristics of ocular firework casualties were obtained
      and incidence rates of sustained trauma and vision loss calculated. RESULTS:
      Twenty-six relevant articles were suitable for calculation of trauma incidence
      and patient demographics, of which 17 articles could be used for calculating
      trauma severity and vision loss. Victims were male (77%), young (82%) and often
      bystander (47%). Most of the trauma was mild and temporary. Penetrating eye
      trauma, globe contusions and burns accounted for 18.2%, with a 3.9% enucleation
      rate. Mean visual acuity was >10/20 in 56.8%, with severe vision loss (<10/200)
      in 16.4%. Countries using restrictive firework legislation show 87% less eye
      trauma (p<0.005). CONCLUSIONS: One in six ocular firework traumas show severe
      vision loss, mostly in young males. Bystanders are as frequently injured.
      Firework traumas are a preventable cause of severe ocular injury and blindness
      because countries using restrictive firework legislation have remarkable lower
      trauma incidence rates.

PMID- 19846416
TI  - Acute hemodynamic effects of recruitment maneuvers in patients with acute
      respiratory distress syndrome.
AB  - BACKGROUND: The recruitment maneuver (RM) in acute respiratory distress syndrome
      (ARDS) can cause hemodynamic derangement. We evaluated circulatory and cardiac
      changes during RMs. METHODS: We performed sustained inflation (SI) with a
      pressure of 40 cm H(2)O for 30 seconds as an RM on 22 patients with ARDS. Blood
      pressure (BP) and heart rate were recorded immediately before, every 10 seconds
      during, and 30 seconds after the RM. Ventricular dimensions were obtained
      simultaneously using M-mode echocardiography, and tissue Doppler imaging was
      performed on the left ventricular wall. RESULTS: Mean, systolic, and diastolic BP
      decreased at 20 and 30 seconds during 30-second RMs (mean BP: 92 +/- 12 at
      baseline to 83 +/- 18 mm Hg at the end of the RM, P < .05) and subsequently
      recovered. Heart rate decreased at 10 and 20 seconds during the RM, and tended to
      increase afterward. Both ventricular dimensions decreased significantly during
      the RM. The left ventricular ejection fraction and peak velocity of the left
      ventricle during systole remained stable. The fractional changes in mean BP and
      left ventricular end-diastolic dimension during the RMs were correlated
      significantly with each other (r(s) = 0.59). Static compliance of the respiratory
      system (Crs) was lower in patients with mean BP change > or =15% than in patients
      in whom the change was <15% (P < .05). CONCLUSIONS: A transient decrease in mean
      BP was observed during the RM, and its degree was correlated with the preload
      decrease, while cardiac contractility was maintained.

PMID- 19846417
TI  - A conjugated linoleic acid-enriched beef diet attenuates lipopolysaccharide
      induced inflammation in mice in part through PPARgamma-mediated suppression of
      toll-like receptor 4.
AB  - Conjugated linoleic acid (CLA) is a PUFA found in beef and dairy products that
      has immunoregulatory properties. The level of CLA in beef can be enhanced by
      feeding cattle fresh grass rather than concentrates. This study determined the
      effect of feeding a high-CLA beef diet on inflammation in an in vivo model of
      septic shock. Mice were fed a high-CLA beef (4.3% total fatty acid composition)
      or low-CLA beef diet (0.84% total fatty acid composition) for 6 wk.
      Lipopolysaccharide (LPS; 3 microg) or sterile PBS was injected i.v. and serum was
      harvested 6 h after injection. Serum interleukin (IL)-1beta, IL-12p70, IL-12p40,
      and interferon-gamma concentrations were significantly reduced in response to the
      LPS challenge in the high-CLA beef diet group. Bone marrow-derived dendritic
      cells (BMDC) from the high-CLA beef diet group had significantly less IL-12 and
      more IL-10 in response to ex vivo LPS stimulation. Furthermore, toll-like
      receptor 4 (TLR4) and CD14 protein and mRNA expression on BMDC was significantly
      attenuated in the high-CLA compared with the low-CLA beef diet group.
      Complimentary in vitro experiments to determine the specificity of the effect
      showed that synthetic cis9, trans11-CLA suppressed surface expression of CD14 and
      TLR4 on BMDC. Treatment with the PPARgamma inhibitor GW9662 partially reversed
      TLR4 expression in immature BMDC. The results of this study demonstrate that
      feeding a diet enriched in high-beef CLA exerts profound antiinflammatory effects
      in vivo within the context of LPS-induced sepsis. In addition, downregulation of
      BMDC TLR4 is mediated through induction of PPARgamma.

PMID- 19846418
TI  - Plaque type and composition as evaluated non-invasively by MSCT angiography and
      invasively by VH IVUS in relation to the degree of stenosis.
AB  - BACKGROUND: Imaging of coronary plaques has traditionally focused on evaluating
      degree of stenosis, as the risk for adverse cardiac events increases with
      stenosis severity. However, the relation between plaque composition and severity
      of stenosis remains largely unknown. OBJECTIVE: To assess plaque composition (non
      invasively by multislice computed tomography (MSCT) angiography and invasively by
      virtual histology intravascular ultrasound (VH IVUS)) in relation to degree of
      stenosis. METHODS: 78 patients underwent MSCT (identifying three plaque types;
      non-calcified, calcified, mixed) followed by invasive coronary angiography and VH
      IVUS. VH IVUS evaluated plaque burden, minimal lumen area and plaque composition
      (fibrotic, fibro-fatty, necrotic core, dense calcium) and plaques were classified
      as fibrocalcific, fibroatheroma, thin-capped fibroatheroma (TCFA), pathological
      intimal thickening. For each plaque, percentage stenosis was evaluated by
      quantitative coronary angiography. Significant stenosis was defined >50%
      stenosis. RESULTS: Overall, 43 plaques (19%) corresponded to significant
      stenosis. Of the 227 plaques analysed, 70 were non-calcified plaques (31%), 96
      mixed (42%) and 61 calcified (27%) on MSCT. Plaque types on MSCT were equally
      distributed among significant and non-significant stenoses. VH IVUS identified
      that plaques with significant stenosis had higher plaque burden (67% (11%) vs 53%
      (12%), p<0.05) and smaller minimal lumen area (4.6 (3.8-6.8) mm(2) vs 7.3 (5.4
      10.5) mm(2), p<0.05). Interestingly, no differences were observed in percentage
      fibrotic, fibro-fatty, necrotic core and dense calcium. Non-significant stenoses
      were more frequently classified as pathological intimal thickening (46 (25%) vs 3
      (7%), p<0.05), although TCFA (more vulnerable plaque) was distributed equally (p
      = 0.18). CONCLUSION: No evident association exists between the degree of stenosis
      and plaque composition or vulnerability, as evaluated non-invasively by MSCT and
      invasively by VH IVUS.

PMID- 19846419
TI  - Hypertension and adherence to physical activity programs--a sticky matter!

PMID- 19846420
TI  - Are there risk factors in alpine skiing? A controlled multicentre survey of 1278
      skiers.
AB  - OBJECTIVE: To analyse risk factors in alpine skiing. DESIGN: A controlled
      multicentre survey of injured and non-injured alpine skiers. SETTING: One
      tertiary and two secondary trauma centres in Bern, Switzerland. PATIENTS AND
      METHODS: All injured skiers admitted from November 2007 to April 2008 were
      analysed using a completed questionnaire incorporating 15 parameters. The same
      questionnaire was distributed to non-injured controls. Multiple logistic
      regression was performed. Patterns of combined risk factors were calculated by
      inference trees. A total of 782 patients and 496 controls were interviewed.
      RESULTS: Parameters that were significant for the patients were: high readiness
      for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p =
      0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes
      (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR
      59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to
      2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to
      0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07
      to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10
      to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and
      alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk
      were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and
      bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet;
      (3) warm-up >12 min and new skiing equipment. CONCLUSIONS: Low speed, high
      readiness for risk, new skiing equipment, old and powder snow, and drug
      consumption are significant risk factors when skiing. Future work should aim to
      identify more precisely specific groups at risk and develop recommendations--for
      example, a snow weather index at valley stations.

PMID- 19846421
TI  - The role of the sports and exercise medicine physician in the National Health
      Service: a questionnaire-based survey.
AB  - OBJECTIVES: To investigate the opinions of general practitioners, orthopaedic
      surgeons, rheumatologists, sport and exercise medicine (SEM) registrars and
      public health consultants on training, caseload, the most appropriate setting and
      the position of SEM within the National Health Service (NHS) in the UK. METHOD: A
      cross-sectional questionnaire-based survey investigated the opinions of the above
      professionals from three primary care trusts and associated hospitals in London
      and Birmingham. RESULTS: With a 50% response rate (n = 226), 93% (208/224) of
      participants felt that there was a role for SEM in the NHS. 56% (124/223) agreed
      that this role should be in both primary and secondary care. 64% (136/212) of
      participants felt that their practice would benefit from the input of a SEM
      physician and 95% (191/202) would consider referring patients to SEM services.
      74% (165/222) agreed that SEM should have a public health role, and 63% (140/222)
      believed that these responsibilities should be evenly balanced with the treatment
      of sports injuries. Despite the emphasis on public health work from SEM policy
      makers, none of the SEM registrars selected public health as an important
      training area. 31% (44/140) of participants felt that a lack of education in the
      medical profession regarding SEM represented the greatest hindrance to its
      development in the NHS. CONCLUSION: Several areas of agreement were demonstrated
      across the specialties, many of which matched the views of policy makers. This
      study involved participants from a range of cognate disciplines and was the first
      to investigate this issue since SEM was recognised as a specialty in 2005.

PMID- 19846422
TI  - Women's rugby league injury claims and costs in New Zealand.
AB  - AIM: There is scarce information on rugby league injuries in female players. This
      paper provides an overview of the epidemiology of women's rugby league injuries
      requiring medical treatment and associated costs in New Zealand. METHOD: New
      Zealand Accident Compensation Corporation injury data for the period 1999-2007
      were searched for rugby league injury cases occurring in females. Data were
      analysed by demographics, body region, nature/severity of injury, and medical
      procedure and costs. RESULTS: There were 320 moderate to serious injury claims
      recorded for females participating in rugby league activities over the study
      period. There was a mean (SD) of 37.9 (9.5) injury claims per year. The mean cost
      per year for the study period was $196 514 ($99,133) (L76,066 (L38,374)) with
      half of the injury claims occurring in New Zealand Maori. Concussion/brain
      injuries accounted for 3.8% of total female moderate to serious injury claims but
      accounted for 5.4% of female injury costs ($84,399 (L32,688)) with the highest
      mean cost per claim ($7033 (L2724)). The lower limb accounted for 65% of the
      total female injury claims and 58.7% of total injury costs ($922,296 (L356,968)).
      The mean cost per claim was higher for the lower limb ($4434 (L1714)) than the
      upper ($3331 (L1288)) limb. Clerks recorded 16.3% of the total injury claims,
      20.3% of total injury costs ($319,474 (L123,211)) and had the highest mean cost
      per claim ($6144 (L2370)). The 25-29 age group recorded 31.9% of injury claims
      and 33.8% of injury costs. The 35-39 age group recorded the highest mean cost per
      claim ($6200 (L2392)) but only 10.9% of total claims and 13.8% of total costs.
      DISCUSSION: When compared with other studies in rugby league injuries, it appears
      that females incur substantially fewer injuries (5.7%) than males (94.3%).
      Although no participation data by sex are available, it is likely that
      participation percentages are reflected in the injury percentages. The high
      frequency (65%) and cost proportion (58.7%) for lower limb injuries was higher in
      females than in male rugby league players (previously reported as 42.4% of the
      injury claims and 31.5% of the total injury claim costs for the lower limb).
      CONCLUSIONS: Injury prevention programmes for women's rugby league should focus
      on the 25-29 age group and address ways to prevent concussion and lower limb
      injuries.

PMID- 19846423
TI  - Physical fitness and indices of lifestyle-related diseases before and after
      interval walking training in middle-aged and older males and females.
AB  - HYPOTHESIS: Whether increasing peak aerobic capacity for walking (VO(2peak)) by
      interval walking training (IWT) is closely linked with decreasing the indices of
      lifestyle-related diseases (LSDs) in middle-aged and older people were examined.
      METHODS: For 4 months from April to September 2005 or 2006, 246 males and 580
      females (~65 years) performed IWT consisting of >=5 sets of fast walking at >=70%
      VO(2peak) for 3 min followed by slow walking at <=40% VO(2peak) for 3 min >=4
      days/week. Before and after IWT, we measured VO(2peak), body mass index (BMI),
      %body fat, arterial blood pressure, thigh muscle strength and blood parameters.
      We analysed 198 males and 468 females who had undergone all the measurements both
      before and after IWT. To examine the hypothesis, we divided the subjects equally
      into three groups according to their pretraining VO(2peak): low, middle and high
      groups for each sex. RESULTS: Before training, it was found that thigh muscle
      strength and blood high-density lipoprotein cholesterol concentration were lower,
      whereas body weight, BMI, %body fat, arterial blood pressure and blood glucose
      were higher in the low group than the high group (all, p<0.05). After training,
      although VO(2peak) and thigh muscle strength increased and body weight, BMI,
      %body fat, blood pressure and blood glucose concentration decreased in all groups
      (all, p<0.05), the changes were greatest in the low group for both sexes.
      CONCLUSION: VO(2peak) at baseline and changes in response to training were
      closely linked with indices of LSDs.

PMID- 19846424
TI  - Changes of mucosal immunity and antioxidation activity in elite male Taiwanese
      taekwondo athletes associated with intensive training and rapid weight loss.
AB  - OBJECTIVE: The aim of this study was to investigate the cumulative effects of
      prolonged, intensive training and rapid weight loss on immunological parameters
      and antioxidation activity of elite male Taiwanese taekwondo athletes. DESIGN: 16
      Elite male taekwondo athletes (mean age, 21.6 (1.3) years; mean height, 173.7
      (5.5) cm) volunteered to participate in this study. Beginning at 30 days before a
      national competition, saliva samples were obtained during a 7-week training, the
      competition and the postcompetition period. Levels of salivary IgA, cortisol,
      lactoferrin and free-radical scavenging activity were measured at 30-, 14-, 7-
      and 1-day precompetition and 1-, 7- and 19-day postcompetition. Body weight and
      body fat were also recorded. RESULTS: The mean body weight was notably decreased
      during the week immediately before the competition. Results reveal that the
      levels of salivary IgA were differentially regulated during the training,
      competition and recovery period, while the salivary cortisol and lactoferrin
      concentrations and free-radical scavenging activity were not appreciably affected
      during the training and the competition period. Furthermore, the results of an
      upper respiratory tract infection incidence indicate that following the decreases
      of mucosal immunity, the risk of acquiring infection was significantly increased.
      CONCLUSIONS: Our results demonstrated that mucosal immunity in elite male
      taekwondo athletes is modulated by exercise and rapid weight reduction during the
      training, competition and recovery period. Cumulative effects of prolonged
      intensive training and rapid weight reduction suppressed mucosal immunity.
      Furthermore, because of the "open window" of impaired immunity during the
      precompetition period, the incidence of upper respiratory tract infection was
      significantly increased after the competition.

PMID- 19846425
TI  - Controversies relating to preparticipation cardiovascular screening in young
      athletes: time for a realistic solution?

PMID- 19846426
TI  - Ten years of evidence to guide physiotherapy interventions: Physiotherapy
      Evidence Database (PEDro).

PMID- 19846427
TI  - Exercise and diet in weight management: updating what works.
AB  - The world is facing major problems associated with the rapid increase in levels
      of overweight and obesity. Solving this problem via appropriate modifications to
      exercise habits and/or diet appears easy, but in practice it is inordinately
      difficult and only a small percentage manage to maintain their weight loss over
      the long term. However, a number of strategies can be used to increase the
      chances of success. Medical doctors, dieticians and other allied health
      professionals are potentially well placed to provide guidance to those at risk of
      overweight/obesity. This review is aimed at supporting major initiatives
      targeting an increase in community physical activity to help reduce the
      prevalence of overweight/obesity, such as the "Change4Life" campaign in the UK
      (http://www.nhs.uk/change4life) and the "Exercise is Medicine" campaign in the
      USA (http://www.exerciseismedicine.org). By providing a concise summary of the
      evidence-based research that can be easily understood by a wide range of health
      professionals, this review hopes to provide a useful document that can be used to
      enhance preventive counselling by promoting appropriate changes in lifestyle that
      will ultimately increase levels of physical activity, as well as reduce levels of
      overweight/obesity and other associated chronic hypokinetic conditions.

PMID- 19846428
TI  - Exercise and heat stress: performance, fatigue and exhaustion--a hot topic.

PMID- 19846429
TI  - Genotype-phenotype correlations in L1 syndrome: a guide for genetic counselling
      and mutation analysis.
AB  - OBJECTIVES: To develop a comprehensive mutation analysis system with a high rate
      of detection, to develop a tool to predict the chance of detecting a mutation in
      the L1CAM gene, and to look for genotype-phenotype correlations in the X-linked
      recessive disorder, L1 syndrome. METHODS: DNA from 367 referred patients was
      analysed for mutations in the coding sequences of the gene. A subgroup of 100
      patients was also investigated for mutations in regulatory sequences and for
      large duplications. Clinical data for 106 patients were collected and used for
      statistical analysis. RESULTS: 68 different mutations were detected in 73
      patients. In patients with three or more clinical characteristics of L1 syndrome,
      the mutation detection rate was 66% compared with 16% in patients with fewer
      characteristics. The detection rate was 51% in families with more than one
      affected relative, and 18% in families with one affected male. A combination of
      these two factors resulted in an 85% detection rate (OR 10.4, 95% CI 3.6 to
      30.1). The type of mutation affects the severity of L1 syndrome. Children with a
      truncating mutation were more likely to die before the age of 3 than those with a
      missense mutation (52% vs 8%; p=0.02). CONCLUSIONS: We developed a comprehensive
      mutation detection system with a detection rate of almost 20% in unselected
      patients and up to 85% in a selected group. Using the patients' clinical
      characteristics and family history, clinicians can accurately predict the chance
      of finding a mutation. A genotype-phenotype correlation was confirmed. The
      occurrence of (maternal) germline mosaicism was proven.

PMID- 19846431
TI  - Cryoablation time-dependent dose-response effect at minimal temperatures (-80
      degrees C): an experimental study.
AB  - AIMS: To establish a temporal safety window for cryoablation at minimal
      temperatures and to assess the electrophysiological and histological changes as a
      function of the application duration. METHODS AND RESULTS: Twenty mini-pigs
      underwent AV nodal cryoablation at -80 degrees C without prior cryomapping. The
      duration of the cryoapplication following atrioventricular block (AVB) was
      randomized to 0, 10, 20, 40, or 60 s. Atrioventricular block was obtained in all
      animals after a median of 3 (1-8 interquartile range) applications. One week
      later, AV nodal conduction fully recovered in animals with application duration
      <10 s, whereas persistent AVB incidence increased as a function of time in
      animals with longer applications duration. Cryoablation application duration
      following AVB was the only independent predictor of persistent AVB (OR, 1.116;
      95% CI, 1.013-1.229; P = 0.026). There was no difference in lesion location or
      size between animals with vs. those without persistent AVB at 1 week. However,
      animals randomized to longer application duration demonstrated higher degree of
      cell destruction and fibrotic content. CONCLUSION: In this closed-chest pig
      model, there was a relation between cryoapplication duration following AVB at -80
      degrees C and recovery of conduction. A safety window of at least 10 s was
      observed in all cases.

PMID- 19846432
TI  - Radiation exposure to patients' skin during cardiac resynchronization therapy.
AB  - AIMS: The purpose of the current study is to evaluate the patients' entrance skin
      dose (ESD) during cardiac resynchronization therapy (CRT). METHODS AND RESULTS:
      Entrance skin doses were assessed during 16 CRT procedures. Seven of the 16
      patients were upgrade of conventional pacemaker to CRT. The patients wore jackets
      which had 100 radiosensitive indicators placed on the back during the procedures.
      After the procedure, the patients' ESDs were calculated from the colour
      difference of the indicators. Eleven of the 16 patients were implanted devices
      with a defibrillator, and three patients those without a defibrillator. In the
      other two, the procedures failed. The average total fluoroscopic time (TFT),
      total numbers of cine frames, and the maximum ESDs were 56.7 +/- 28.0 min, 674 +/
      342 frames, and 1.0 +/- 0.6 Gy, respectively. Of the 16 patients, six received
      ESDs exceeding 1 Gy, TFT, total number of cine frames, and the maximum ESD tended
      to decrease as the operator experience increased. CONCLUSION: The patients' ESDs
      during CRT procedures can exceed the thresholds for radiation skin injuries due
      to prolonged fluoroscopic times. Therefore, interventionalists should estimate
      the doses.

PMID- 19846433
TI  - Dppa2 knockdown-induced differentiation and repressed proliferation of mouse
      embryonic stem cells.
AB  - Developmental pluripotency-associated 2 (Dppa2) gene is one of the genes recently
      identified to be expressed specifically in pluripotent cells. To investigate the
      role of Dppa2 in mouse embryonic stem (ES) cells, we examined its expression
      during differentiation and performed knockdown of Dppa2 in mouse ES cells. Our
      results showed that the expression of Dppa2 decreased markedly in differentiated
      cells. Dppa2 knockdown induced the differentiation of mouse ES cells, as
      indicated by reduced alkaline phosphatase activity, slightly downregulated
      expression of the putative pluripotency marker genes Oct4 and Nanog and increased
      expression of early differentiation marker genes, such as Fst and Psx1. Moreover,
      reduced expression of Dppa2 also repressed cell proliferation activity as shown
      by the 5-bromo-2-deoxyuridine incorporation assay. Hence, Dppa2 might play a role
      in maintenance of the undifferentiated state and proliferation of ES cells.

PMID- 19846434
TI  - Site-directed mutation at residues near the catalytic site of histamine
      dehydrogenase from Nocardioides simplex and its effects on substrate inhibition.
AB  - Histamine dehydrogenase from Nocardioides simplex (nHmDH) is a homodimer
      containing one 6-S-cysteinyl FMN (CFMN) and one [4Fe-4S] cluster per monomer.
      nHmDH catalyses the oxidative deamination of histamine to ammonia and imidazole
      acetaldehyde, but histamine inhibits its catalytic activity at high
      concentrations. We mutated gene-encoded residues (Tyr180, Gly268 and Asp269) near
      CFMN to understand the biophysical meaning of the substrate inhibition. Three
      mutants Y180F, G268D/D269C and Y180F/G268D/D269C were expressed by considering
      the DNA sequence alignment of histamine dehydrogenase from Rhizobium sp. 4-9
      (rHmDH), which does not suffer from the substrate inhibition. The
      Y180F/G268D/D269C mutation to mimic rHmDH successfully suppressed the inhibition,
      although the catalytic activity decreased. The substrate inhibition was weakened
      by the Y180F mutation, but G268D/D269C was still susceptible to the inhibition.
      It was found that it also causes changes in the UV-vis absorption spectra of the
      substrate-reduced form and the redox potential of the enzymes. The
      characterization suggests that the thermodynamic preference of the semiquinone
      form of CFMN in the two-electron-reduced subunit of the enzyme is responsible for
      the substrate inhibition. However, destabilization of the semiquinone form leads
      to kinetic hindrance due to the uphill single electron transfer from the fully
      reduced CFMN to the [4Fe-4S] cluster.

PMID- 19846435
TI  - CRISPI: a CRISPR interactive database.
AB  - SUMMARY: The CRISPR genomic structures (Clustered Regularly Interspaced Short
      Palindromic Repeats) form a family of repeats that is largely present in archaea
      and frequent in bacteria. On the basis of a formal model of CRISPR using very few
      parameters, a systematic study of all their occurrences in all available genomes
      of Archaea and Bacteria has been carried out. This has resulted in a relational
      database, CRISPI, which also includes a complete repertory of associated CRISPR
      associated genes (CAS). A user-friendly web interface with many graphical tools
      and functions allows users to extract results, find CRISPR in personal sequences
      or calculate sequence similarity with spacers. AVAILABILITY: CRISPI free access
      at http://crispi.genouest.org CONTACT: croussea@irisa.fr; jnicolas@irisa.fr

PMID- 19846436
TI  - Reporting bias when using real data sets to analyze classification performance.
AB  - MOTIVATION: It is commonplace for authors to propose a new classification rule,
      either the operator construction part or feature selection, and demonstrate its
      performance on real data sets, which often come from high-dimensional studies,
      such as from gene-expression microarrays, with small samples. Owing to the
      variability in feature selection and error estimation, individual reported
      performances are highly imprecise. Hence, if only the best test results are
      reported, then these will be biased relative to the overall performance of the
      proposed procedure. RESULTS: This article characterizes reporting bias with
      several statistics and computes these statistics in a large simulation study
      using both modeled and real data. The results appear as curves giving the
      different reporting biases as functions of the number of samples tested when
      reporting only the best or second best performance. It does this for two
      classification rules, linear discriminant analysis (LDA) and 3-nearest-neighbor
      (3NN), and for filter and wrapper feature selection, t-test and sequential
      forward search. These were chosen on account of their well-studied properties and
      because they were amenable to the extremely large amount of processing required
      for the simulations. The results across all the experiments are consistent: there
      is generally large bias overriding what would be considered a significant
      performance differential, when reporting the best or second best performing data
      set. We conclude that there needs to be a database of data sets and that, for
      those studies depending on real data, results should be reported for all data
      sets in the database. AVAILABILITY: Companion web site at
      http://gsp.tamu.edu/Publications/supplementary/yousefi09a/

PMID- 19846437
TI  - Accurate confidence aware clustering of array CGH tumor profiles.
AB  - MOTIVATION: Chromosomal aberrations tend to be characteristic for given
      (sub)types of cancer. Such aberrations can be detected with array comparative
      genomic hybridization (aCGH). Clustering aCGH tumor profiles aids in identifying
      chromosomal regions of interest and provides useful diagnostic information on the
      cancer type. An important issue here is to what extent individual aCGH tumor
      profiles can be reliably assigned to clusters associated with a given cancer
      type. RESULTS: We introduce a novel evolutionary fuzzy clustering (EFC)
      algorithm, which is able to deal with overlapping clusterings. Our method
      assesses these overlaps by using cluster membership degrees, which we use here as
      a confidence measure for individual samples to be assigned to a given tumor type.
      We first demonstrate the usefulness of our method using a synthetic aCGH dataset
      and subsequently show that EFC outperforms existing methods on four real datasets
      of aCGH tumor profiles involving four different cancer types. We also show that
      in general best performance is obtained using 1- Pearson correlation coefficient
      as a distance measure and that extra preprocessing steps, such as segmentation
      and calling, lead to decreased clustering performance. AVAILABILITY: The source
      code of the program is available from http://ibi.vu.nl/programs/efcwww

PMID- 19846438
TI  - Targeted interrogation of copy number variation using SCIMMkit.
AB  - SUMMARY: Copy number variants (CNVs) contribute substantially to human genomic
      diversity, and development of accurate and efficient methods for CNV genotyping
      is a central problem in exploring human genotype-phenotype associations. SCIMMkit
      provides a robust, integrated implementation of three previously validated
      algorithms [SCIMM (SNP-Conditional Mixture Modeling), SCIMM-Search and SCOUT (SNP
      Conditional OUTlier detection)] for targeted interrogation of CNVs using Illumina
      Infinium II and GoldenGate SNP assays. SCIMMkit is applicable to standardized
      genome-wide SNP arrays and customized multiplexed SNP panels, providing economy,
      efficiency and flexibility in experimental design. AVAILABILITY: Source code and
      documentation are available for noncommercial use at
      http://droog.gs.washington.edu/scimmkit.

PMID- 19846439
TI  - G-compass: a web-based comparative genome browser between human and other
      vertebrate genomes.
AB  - SUMMARY: G-compass is designed for efficient comparative genome analysis between
      human and other vertebrate genomes. The current version of G-compass allows us to
      browse two corresponding genomic regions between human and another species in
      parallel. One-to-one evolutionarily conserved regions (i.e. orthologous regions)
      between species are highlighted along the genomes. Information such as locations
      of duplicated regions, copy number variations and mammalian ultra-conserved
      elements is also provided. These features of G-compass enable us to easily
      determine patterns of genomic rearrangements and changes in gene orders through
      evolutionary time. Since G-compass is a satellite database of H-InvDB, which is a
      comprehensive annotation resource for human genes and transcripts, users can
      easily refer to manually curated functional annotations and other abundant
      biological information for each human transcript. G-compass is expected to be a
      valuable tool for comparing human and model organisms and promoting the exchange
      of functional information. AVAILABILITY: G-compass is freely available at
      http://www.h-invitational.jp/g-compass/. CONTACT: t.imanishi@aist.go.jp

PMID- 19846440
TI  - Roll: a new algorithm for the detection of protein pockets and cavities with a
      rolling probe sphere.
AB  - MOTIVATION: Prediction of ligand binding sites of proteins is significant as it
      can provide insight into biological functions and reaction mechanisms of
      proteins. It is also a prerequisite for protein-ligand docking and an important
      step in structure-based drug design. RESULTS: We present a new algorithm, Roll,
      implemented in a program named POCASA, which can predict binding sites by
      detecting pockets and cavities of proteins with a rolling sphere. To evaluate the
      performance of POCASA, a test with the same data set as used in several existing
      methods was carried out. POCASA achieved a high success rate of 77%. In addition,
      the test results indicated that POCASA can predict good shapes of ligand binding
      sites. AVAILABILITY: A web version of POCASA is freely available at
      http://altair.sci.hokudai.ac.jp/g6/Research/POCASA_e.html.

PMID- 19846442
TI  - Bioresponsive nanosensors in medical imaging.
AB  - Superparamagnetic iron oxide nanoparticles have been established as sensitive
      probes for magnetic resonance imaging (MRI). While the majority of specific
      nanosensors are based on sterically stabilized iron oxide particles, the focus of
      this review is on the use of very small iron oxide particles (VSOPs) that are
      electrostatically stabilized by an anionic citrate acid shell. We used VSOPs to
      develop target-specific as well as protease-activatable nanosensors for molecular
      MRI.

PMID- 19846441
TI  - Perspective on post-menopausal osteoporosis: establishing an interdisciplinary
      understanding of the sequence of events from the molecular level to whole bone
      fractures.
AB  - Current drug treatments for post-menopausal osteoporosis cannot eliminate bone
      fractures, possibly because the mechanisms responsible for bone loss are not
      fully understood. Although research within various disciplines has significantly
      advanced the state of knowledge, fundamental findings are not widely understood
      between different disciplines. For that reason, this paper presents noteworthy
      experimental findings from discrete disciplines focusing on post-menopausal
      osteoporosis. These studies have established that, in addition to bone loss,
      significant changes in bone micro-architecture, tissue composition and micro
      damage occur. Cellular processes and molecular signalling pathways governing
      pathological bone resorption have been identified to a certain extent. Ongoing
      studies endeavour to determine how such changes are initiated at the onset of
      oestrogen deficiency. It emerges that, because of the discrete nature of previous
      research studies, the sequence of events that lead to bone fracture is not fully
      understood. In this paper, two sequences of multi-scale changes are proposed and
      the experimental challenges that need to be overcome to fully define this
      sequence are outlined. Future studies must comprehensively characterize the time
      sequence of molecular-, cellular- and tissue-level changes to attain a coherent
      understanding of the events that ultimately lead to bone fracture and inform the
      future development of treatments for post-menopausal osteoporosis.

PMID- 19846444
TI  - Pyoderma gangrenosum associated with chronic idiopathic myelofibrosis after
      coronary artery bypass graft surgery.
AB  - Pyoderma gangrenosum (PG) is an ulceronecrotizing dermatosis that can occur after
      minor trauma or surgery and is rare after cardiac surgery. We report a case of PG
      after coronary artery bypass grafting (CABG) in a patient with chronic idiopathic
      myelofibrosis (CIMF). Diagnosis was made with punch skin biopsy and he was
      treated with systemic steroids. His lesions showed remarkable improvement with
      this therapy. Cardiothoracic surgeons need to consider this diagnosis in all
      rapidly expanding postoperative lesions, especially those that do not improve
      with debridement or antibiotics or conservative wound care.

PMID- 19846443
TI  - Nanoparticle interaction with model lung surfactant monolayers.
AB  - One of the most important functions of the lung surfactant monolayer is to form
      the first line of defence against inhaled aerosols such as nanoparticles (NPs),
      which remains largely unexplored. We report here, for the first time, the
      interaction of polyorganosiloxane NPs (AmorSil20: 22 nm in diameter) with lipid
      monolayers characteristic of alveolar surfactant. To enable a better
      understanding, the current knowledge about an established model surface film that
      mimics the surface properties of the lung is reviewed and major results
      originating from our group are summarized. The pure lipid components
      dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol have been used
      to study the biophysical behaviour of their monolayer films spread at the air
      water interface in the presence of NPs. Film balance measurements combined with
      video-enhanced fluorescence microscopy have been used to investigate the
      formation of domain structures and the changes in the surface pattern induced by
      NPs. We are able to show that NPs are incorporated into lipid monolayers with a
      clear preference for defect structures at the fluid-crystalline interface leading
      to a considerable monolayer expansion and fluidization. NPs remain at the air
      water interface probably by coating themselves with lipids in a self-assembly
      process, thereby exhibiting hydrophobic surface properties. We also show that the
      domain structure in lipid layers containing surfactant protein C, which is
      potentially responsible for the proper functioning of surfactant material, is
      considerably affected by NPs.

PMID- 19846445
TI  - Endobronchial schwannoma presenting with bronchial obstruction.
AB  - Schwannomas are relatively uncommon, benign nerve sheath tumors. Thoracic
      schwannomas most often appear in the posterior mediastinum. Pulmonary schwannomas
      are exceedingly rare and can present a diagnostic challenge. We present a case of
      an endobronchial schwannoma presenting with bronchial obstruction and review the
      literature of this unusual entity.

PMID- 19846446
TI  - Do female ornaments indicate quality in eider ducks?
AB  - The fitness consequences of female ornamentation remain little studied and the
      results are often contradictory. Female ornamentation may be an artefact of a
      genetic correlation with male ornamentation, but this possibility can be
      disregarded if the ornament only occurs in females. Female-specific white wing
      bars in eiders (Somateria mollissima) have been suggested to indicate individual
      quality, and we studied size variation in this trait in relation to key fitness
      components and quality attributes. We found that clutch size, body condition,
      female age, hatching date and success were unrelated to female ornament size;
      ornament size was explained by its size in the previous year. In contrast, good
      body condition was associated with hatching success. These results suggest that
      the breadth of the white wing bars does not indicate individual quality in our
      study population.

PMID- 19846447
TI  - Inbreeding depression in adaptive plasticity under predation risk in a freshwater
      snail.
AB  - While much attention has been paid to the effects of inbreeding on fitness, this
      has mostly come from a genetic perspective. Consequently, the interaction between
      inbreeding and the environment is less well understood. To understand the effects
      of inbreeding in natural populations where environmental conditions are variable,
      we need to examine not only how the effects of inbreeding change among
      environments but also how inbreeding may affect the ability to respond to
      environmental conditions (i.e. phenotypic plasticity). We reared selfed and
      outcrossed hermaphroditic snails (Physa acuta) in the presence and absence of
      chemical cues from predatory crayfish and quantified expression of an inducible
      defence, an adaptively plastic response to predation risk. Overall, inbred snails
      exhibited reduced defences, but more importantly, inbreeding reduced the
      expression of predator-induced adaptive plasticity. Inbreeding depression in
      defensive morphology was 26 per cent and inbreeding depression in the plasticity
      of this trait was 48 per cent. Inbreeding depression in adaptive plasticity may
      be important to understanding the effects of inbreeding in nature.

PMID- 19846448
TI  - Phagocytic B cells in a reptile.
AB  - Evidence for a developmental relationship between B cells and macrophages has led
      to the hypothesis that B cells evolved from a phagocytic predecessor. The recent
      identification of phagocytic IgM+ cells in fishes and amphibians supports this
      hypothesis, but raises the question of when, evolutionarily, was phagocytic
      capacity lost in B cells? To address this, leucocytes were isolated from red
      eared sliders, Trachemys scripta, incubated with fluorescent beads and analysed
      using flow cytometry and confocal microscopy. Results indicate that red-eared
      slider B cells are able to ingest foreign particles and suggest that ectothermic
      vertebrates may use phagocytic B cells as part of a robust innate immune
      response.

PMID- 19846449
TI  - Repeatability of nest morphology in African weaver birds.
AB  - It is generally assumed that birds build nests according to a genetic 'template',
      little influenced by learning or memory. One way to confirm the role of genetics
      in nest building is to assess the repeatability of nest morphology with repeated
      nest attempts. Solitary weaver birds, which build multiple nests in a single
      breeding season, are a useful group with which to do this. Here we show that
      repeatability of nest morphology was low, but significant, in male Southern
      Masked weaver birds and not significant in the Village weavers. The larger bodied
      Village weavers built larger nests than did Southern Masked weavers, but body
      size did not explain variation in Southern Masked weaver nest dimensions. Nests
      built by the same male in both species got shorter and lighter as more nests were
      constructed. While these data demonstrate the potential for a genetic component
      of variation in nest building in solitary weavers, it is also clear that there
      remains plenty of scope in both of these species for experience to shape nest
      construction.

PMID- 19846450
TI  - Post-glacial redistribution and shifts in productivity of giant kelp forests.
AB  - Quaternary glacial-interglacial cycles create lasting biogeographic, demographic
      and genetic effects on ecosystems, yet the ecological effects of ice ages on
      benthic marine communities are unknown. We analysed long-term datasets to develop
      a niche-based model of southern Californian giant kelp (Macrocystis pyrifera)
      forest distribution as a function of oceanography and geomorphology, and
      synthesized palaeo-oceanographic records to show that late Quaternary climate
      change probably drove high millennial variability in the distribution and
      productivity of this foundation species. Our predictions suggest that kelp forest
      biomass increased up to threefold from the glacial maximum to the mid-Holocene,
      then rapidly declined by 40-70 per cent to present levels. The peak in kelp
      forest productivity would have coincided with the earliest coastal archaeological
      sites in the New World. Similar late Quaternary changes in kelp forest
      distribution and productivity probably occurred in coastal upwelling systems
      along active continental margins worldwide, which would have resulted in complex
      shifts in the relative productivity of terrestrial and marine components of
      coastal ecosystems.

PMID- 19846451
TI  - Urban noise and the cultural evolution of bird songs.
AB  - In urban environments, anthropogenic noise can interfere with animal
      communication. Here we study the influence of urban noise on the cultural
      evolution of bird songs. We studied three adjacent dialects of white-crowned
      sparrow songs over a 30-year time span. Urban noise, which is louder at low
      frequencies, increased during our study period and therefore should have created
      a selection pressure for songs with higher frequencies. We found that the minimum
      frequency of songs increased both within and between dialects during the 30-year
      time span. For example, the dialect with the highest minimum frequency is in the
      process of replacing another dialect that has lower frequency songs. Songs with
      the highest minimum frequency were favoured in this environment and should have
      the most effective transmission properties. We suggest that one mechanism that
      influences how dialects, and cultural traits in general, are selected and
      transmitted from one generation to the next is the dialect's ability to be
      effectively communicated in the local environment.

PMID- 19846452
TI  - Reelin and apolipoprotein E receptor 2 in the embryonic and mature brain: effects
      of an evolutionary change in the apoER2 gene.
AB  - In the mature cerebral cortex of higher vertebrates, neurons are arranged in
      layers, each layer containing neurons of the same functional class. The cortical
      layering pattern is laid down during development by migration of young post
      mitotic neurons along glial fibres to their correct positions in the cortical
      plate. The mechanics of whole-cell movement are well understood, but there is
      still uncertainty as to how a migrating neuron is instructed to leave its glial
      support when it reaches its destination. An intraneuronal signalling pathway
      initiated by reelin and containing apolipoprotein E receptor 2 (apoER2) is
      essential for normal cortical layering, and there is strong evidence that
      detachment of a migrating neuron is brought about by reelin-dependent
      downregulation of alpha3 integrin. But there remains the problem of how the
      reelin signal is switched on at a position in the cortex appropriate for each
      class of neuron. ApoER2 of placental mammals contains an amino acid sequence that
      is encoded in a separate exon in the apoER2 gene and is required for normal
      memory and spatial learning. The separate exon is not present in marsupials,
      birds or reptiles. The addition of this exon to the evolving apoER2 gene may have
      contributed to the success of placental mammals.

PMID- 19846453
TI  - A look into the invisible: ultraviolet-B sensitivity in an insect (Caliothrips
      phaseoli) revealed through a behavioural action spectrum.
AB  - Caliothrips phaseoli, a phytophagous insect, detects and responds to solar
      ultraviolet-B radiation (UV-B; lambda <or= 315 nm) under field conditions. A
      highly specific mechanism must be present in the thrips visual system in order to
      detect this narrow band of solar radiation, which is at least 30 times less
      abundant than the UV-A (315-400 nm), to which many insects are sensitive. We
      constructed an action spectrum of thrips responses to light by studying their
      behavioural reactions to monochromatic irradiation under confinement conditions.
      Thrips were maximally sensitive to wavelengths between 290 and 330 nm; human
      visible wavelengths (lambda >or= 400 nm) failed to elicit any response. All but
      six ommatidia of the thrips compound eye were highly fluorescent when exposed to
      UV-A of wavelengths longer than 330 nm. We hypothesized that the fluorescent
      compound acts as an internal filter, preventing radiation with lambda > 330 nm
      from reaching the photoreceptor cells. Calculations based on the putative filter
      transmittance and a visual pigment template of lambda(max) = 360 nm produced a
      sensitivity spectrum that was strikingly similar to the action spectrum of UV
      induced behavioural response. These results suggest that specific UV-B vision in
      thrips is achieved by a standard UV-A photoreceptor and a sharp cut-off internal
      filter that blocks longer UV wavelengths in the majority of the ommatidia.

PMID- 19846454
TI  - The increased risk of predation enhances cooperation.
AB  - Theory predicts that animals in adverse conditions can decrease individual risks
      and increase long-term benefits by cooperating with neighbours. However, some
      empirical studies suggest that animals often focus on short-term benefits, which
      can reduce the likelihood that they will cooperate with others. In this
      experimental study, we tested between these two alternatives by evaluating
      whether increased predation risk (as a correlate of environmental adversity)
      enhances or diminishes the occurrence of cooperation in mobbing, a common anti
      predator behaviour, among breeding pied flycatchers Ficedula hypoleuca. We tested
      whether birds would join their mobbing neighbours more often and harass a stuffed
      predator placed near their neighbours' nests more intensely in areas with a
      higher perceived risk of predation. Our results show that birds attended mobs
      initiated by their neighbours more often, approached the stuffed predator
      significantly more closely, and mobbed it at a higher intensity in areas where
      the perceived risk of predation was experimentally increased. In such high-risk
      areas, birds also were more often involved in between-pair cooperation. This
      study demonstrates the positive impact of predation risk on cooperation in
      breeding songbirds, which might help in explaining the emergence and evolution of
      cooperation.

PMID- 19846455
TI  - History-dependent properties of skeletal muscle myofibrils contracting along the
      ascending limb of the force-length relationship.
AB  - There is a history dependence of skeletal muscle contraction: stretching
      activated muscles induces a long-lasting force enhancement, while shortening
      activated muscles induces a long-lasting force depression. These history
      dependent properties cannot be explained by the current model of muscle
      contraction, and its mechanism is unknown. The purposes of this study were (i) to
      evaluate if force enhancement and force depression are present at short lengths
      (the ascending limb of the force-length (FL) relationship), (ii) to evaluate if
      the history-dependent properties are associated with sarcomere length (SL) non
      uniformity and (iii) to determine the effects of cross-bridge (de)activation on
      force depression. Rabbit psoas myofibrils were isolated and attached between two
      microneedles for force measurements. Images of the myofibrils were projected onto
      a linear photodiode array for measurements of SL. Myofibrils were activated by
      either Ca(2+) or MgADP; the latter induces cross-bridge attachment to actin
      independently of Ca(2+). Activated myofibrils were subjected to three stretches
      or shortenings (approx. 4% SL at approx. 0.07 microm s(-1) sarcomere(-1)) along
      the ascending limb of the FL relationship separated by periods (approx. 5 s) of
      isometric contraction. Force after stretch was higher than force after shortening
      at similar SLs. The differences in force could not be explained by SL non
      uniformity. The FL relationship produced by Ca(2+)- and MgADP-activated
      myofibrils were similar in stretch experiments, but after shortening MgADP
      activation produced forces that were higher than Ca(2+) activation. Since MgADP
      induces the formation of strongly bound cross-bridges, this result suggests that
      force depression following shortening is associated with cross-bridge
      deactivation.

PMID- 19846456
TI  - Stochastic evolutionary dynamics of direct reciprocity.
AB  - Evolutionary game theory is the study of frequency-dependent selection. The
      success of an individual depends on the frequencies of strategies that are used
      in the population. We propose a new model for studying evolutionary dynamics in
      games with a continuous strategy space. The population size is finite. All
      members of the population use the same strategy. A mutant strategy is chosen from
      some distribution over the strategy space. The fixation probability of the mutant
      strategy in the resident population is calculated. The new mutant takes over the
      population with this probability. In this case, the mutant becomes the new
      resident. Otherwise, the existing resident remains. Then, another mutant is
      generated. These dynamics lead to a stationary distribution over the entire
      strategy space. Our new approach generalizes classical adaptive dynamics in three
      ways: (i) the population size is finite; (ii) mutants can be drawn non-locally
      and (iii) the dynamics are stochastic. We explore reactive strategies in the
      repeated Prisoner's Dilemma. We perform 'knock-out experiments' to study how
      various strategies affect the evolution of cooperation. We find that 'tit-for
      tat' is a weak catalyst for the emergence of cooperation, while 'always
      cooperate' is a strong catalyst for the emergence of defection. Our analysis
      leads to a new understanding of the optimal level of forgiveness that is needed
      for the evolution of cooperation under direct reciprocity.

PMID- 19846457
TI  - Re-evaluating the costs and limits of adaptive phenotypic plasticity.
AB  - When the optimal phenotype differs among environments, adaptive phenotypic
      plasticity can evolve unless constraints impede such evolution. Costs and limits
      of plasticity have been proposed as important constraints on the evolution of
      plasticity, yet confusion exists over their distinction. We attempt to clarify
      these concepts by reviewing their categorization and measurement, highlighting
      how costs and limits are defined in different currencies (and may describe the
      same phenomenon). Conclusions from studies that measure the costs of plasticity
      have been equivocal, but we caution that these conclusions may be premature owing
      to a potentially common correlation between environment-specific trait values and
      the magnitude of trait plasticities (i.e. multi-collinearity) that results in
      imprecise and/or biased estimates of the costs. Meanwhile, our understanding of
      the limits of plasticity, and how they may be underlain by the costs of
      plasticity, is still in its infancy. Based on our re-evaluation of these
      constraints, we discuss areas for future research.

PMID- 19846458
TI  - Helping effort increases with relatedness in bell miners, but 'unrelated' helpers
      of both sexes still provide substantial care.
AB  - Indirect fitness benefits from kin selection can explain why non-breeding
      individuals help raise the young of relatives. However, the evolution of helping
      by non-relatives requires direct fitness benefits, for example via group
      augmentation. Here, we examine nest visit rates, load sizes and prey types
      delivered by breeding pairs and their helpers in the cooperatively breeding bell
      miner (Manorina melanophrys). In this system, males remain in their natal colony
      while young females typically disperse, and helpers of both sexes often assist at
      multiple nests concurrently. We found extremely clear evidence for the expected
      effect of genetic relatedness on individual helping effort per nest within
      colonies. This positive incremental effect of kinship was facultative-i.e.
      largely the result of within-individual variation in helping effort.
      Surprisingly, no sex differences were detectable in any aspect of helping, and
      even non-relatives provided substantial aid. Helpers and breeders of both sexes
      regulated their provisioning effort by responding visit-by-visit to changes in
      nestling begging. Helping behaviour in bell miners therefore appears consistent
      with adaptive cooperative investment in the brood, and kin-selected care by
      relatives. Similar investment by 'unrelated' helpers of both sexes argues against
      direct fitness benefits, but is perhaps explained by kin selection at the colony
      level.

PMID- 19846459
TI  - Costly major histocompatibility complex signals produced only by reproductively
      active males, but not females, must be validated by a 'maleness signal' in three
      spined sticklebacks.
AB  - Olfactory information about individual major histocompatibility complex (MHC)
      immune genotypes is important for mate choice in several species. For example,
      during the mate choice decisions of three-spined sticklebacks, females assess
      males on the basis of odour cues that convey information about their MHC
      diversity. Here, we show that an additional 'maleness' signal is needed to
      validate the MHC signal. Furthermore, using interaction between natural odour of
      sticklebacks and synthetic MHC-ligand peptides, we show that MHC signals are
      conditional on the reproductive state in males. By contrast, we find that gravid
      females do not produce such signals. Since MHC olfactory signals relevant to mate
      choice decisions are conditional upon gender and reproductive state, we suggest
      that their manufacture is likely to be costly to senders, and therefore,
      potentially conditional on the health/parasitization status of the sender. We
      hypothesize that shedding of peptide-MHC complexes compromises immune function,
      selecting against unconditional use of these signals.

PMID- 19846460
TI  - Lower limits of ornithischian dinosaur body size inferred from a new Upper
      Jurassic heterodontosaurid from North America.
AB  - The extremes of dinosaur body size have long fascinated scientists. The smallest
      (<1 m length) known dinosaurs are carnivorous saurischian theropods, and
      similarly diminutive herbivorous or omnivorous ornithischians (the other major
      group of dinosaurs) are unknown. We report a new ornithischian dinosaur,
      Fruitadens haagarorum, from the Late Jurassic of western North America that
      rivals the smallest theropods in size. The largest specimens of Fruitadens
      represent young adults in their fifth year of development and are estimated at
      just 65-75 cm in total body length and 0.5-0.75 kg body mass. They are thus the
      smallest known ornithischians. Fruitadens is a late-surviving member of the basal
      dinosaur clade Heterodontosauridae, and is the first member of this clade to be
      described from North America. The craniodental anatomy and diminutive body size
      of Fruitadens suggest that this taxon was an ecological generalist with an
      omnivorous diet, thus providing new insights into morphological and
      palaeoecological diversity within Dinosauria. Late-surviving (Late Jurassic and
      Early Cretaceous) heterodontosaurids are smaller and less ecologically
      specialized than Early (Late Triassic and Early Jurassic) heterodontosaurids, and
      this ecological generalization may account in part for the remarkable 100-million
      year-long longevity of the clade.

PMID- 19846461
TI  - Juvenile sparrows preferentially eavesdrop on adult song interactions.
AB  - Recent research has demonstrated that bird song learning is influenced by social
      factors, but so far has been unable to isolate the particular social variables
      central to the learning process. Here we test the hypothesis that eavesdropping
      on singing interactions of adults is a key social event in song learning by
      birds. In a field experiment, we compared the response of juvenile male song
      sparrows (Melospiza melodia) to simulated adult counter-singing versus simulated
      solo singing. We used radio telemetry to follow the movements of each focal bird
      and assess his response to each playback trial. Juveniles approached the playback
      speakers when exposed to simulated interactive singing of two song sparrows, but
      not when exposed to simulated solo singing of a single song sparrow, which in
      fact they treated similar to heterospecific singing. Although the young birds
      approached simulated counter-singing, neither did they approach closely, nor did
      they vocalize themselves, suggesting that the primary function of approach was to
      permit eavesdropping on these singing interactions. These results indicate that
      during the prime song-learning phase, juvenile song sparrows are attracted to
      singing interactions between adults but not to singing by a single bird and
      suggest that singing interactions may be particularly powerful song-tutoring
      events.

PMID- 19846462
TI  - An inducible morphological defence is a passive by-product of behaviour in a
      marine snail.
AB  - Many organisms have evolved inducible defences in response to spatial and
      temporal variability in predation risk. These defences are assumed to incur large
      costs to prey; however, few studies have investigated the mechanisms and costs
      underlying these adaptive responses. I examined the proximate cause of predator
      induced shell thickening in a marine snail (Nucella lamellosa) and tested whether
      induced thickening leads to an increase in structural strength. Results indicate
      that although predators (crabs) induce thicker shells, the response is a passive
      by-product of reduced feeding and somatic growth rather than an active
      physiological response to predation risk. Physical tests indicate that although
      the shells of predator-induced snails are significantly stronger, the increase in
      performance is no different than that of snails with limited access to food.
      Increased shell strength is attributable to an increase in the energetically
      inexpensive microstructural layer rather than to material property changes in the
      shell. This mechanism suggests that predator-induced shell defences may be
      neither energetically nor developmentally costly. Positive correlations between
      antipredator behaviour and morphological defences may explain commonly observed
      associations between growth reduction and defence production in other systems and
      could have implications for the evolutionary potential of these plastic traits.

PMID- 19846463
TI  - On the use of advanced numerical models for the evaluation of dosimetric
      parameters and the verification of exposure limits at workplaces.
AB  - With the next transposition of the 2004/40/EC Directive, employers will become
      responsible for the electromagnetic field level at the workplace. To make this
      task easier, the scientific community is compiling practical guidelines to be
      followed. This work aims at enriching such guidelines, especially for the
      dosimetric issues. More specifically, some critical aspects related to the
      application of numerical dosimetric techniques for the verification of the safety
      limit compliance have been highlighted. In particular, three different aspects
      have been considered: the dosimetric parameter dependence on the shape and the
      inner characterisation of the exposed subject as well as on the numerical
      algorithm used, and the correlation between reference limits and basic
      restriction. Results and discussions demonstrate how, even by using sophisticated
      numerical techniques, in some cases a complex interpretation of the result is
      mandatory.

PMID- 19846464
TI  - Oocyte peptides as paracrine tools for ovarian stimulation and oocyte maturation.
AB  - Recent studies report the production and isolation of a stable bioactive
      recombinant human bone morphogenetic protein 15 (rhBMP15) that is appropriately
      processed in HEK-293 cells and activates the SMAD 1/5/8 pathway in mouse
      granulosa cell cultures. Further, the purified rhBMP15 induces the expression of
      genes associated with cumulus expansion. Thanks to recent research, we have a
      greater understanding of the importance of the dialogue that occurs between the
      oocyte and the granulosa cell layer with regard to regulating folliculogenesis
      and the acquisition of oocyte developmental competence and maturation. BMP15 is
      one of the critical components of these intra-follicular communication pathways.
      The production of recombinant human BMP15 is important for understanding the
      biochemistry of this specific pathway and for also fully understanding its
      functional contributions to mediating oocyte development. The production of a
      stable recombinant human BMP15 is also important for use in experiments aimed at
      optimizing ovarian stimulation protocols and in vitro oocyte maturation methods.
      This is required to improve oocyte and embryonic developmental competence and
      increase our ability to effectively use in vitro methods for animal production
      and the treatment of human infertility.

PMID- 19846465
TI  - Prolyl 3-hydroxylase 1 and CRTAP are mutually stabilizing in the endoplasmic
      reticulum collagen prolyl 3-hydroxylation complex.
AB  - Null mutations in cartilage-associated protein (CRTAP) and prolyl 3-hydroxylase 1
      (P3H1/LEPRE1) cause types VII and VIII OI, respectively, two novel recessive
      forms of osteogenesis imperfecta (OI) with severe to lethal bone dysplasia and
      overmodification of the type I collagen helical region. CRTAP and P3H1 form a
      complex with cyclophilin B (CyPB) in the endoplasmic reticulum (ER) which 3
      hydroxylates the Pro986 residue of alpha1(I) and alpha1(II) collagen chains. We
      investigated the interaction of complex components in fibroblasts from types VII
      and VIII OI patients. Both CRTAP and P3H1 are absent or reduced on western blots
      and by immunofluorescence microscopy in cells containing null mutations in either
      gene. Levels of LEPRE1 or CRTAP transcripts, however, are normal in CRTAP- or
      LEPRE1-null cells, respectively. Stable transfection of a CRTAP or LEPRE1
      expression construct into cells with null mutations for the transfected cDNA
      restored both CRTAP and P3H1 protein levels. Normalization of collagen helical
      modification in transfected CRTAP-null cells demonstrated that the restored
      proteins functioned effectively as a complex. These data indicate that CRTAP and
      P3H1 are mutually stabilized in the collagen prolyl 3-hydroxylation complex. CyPB
      levels were unaffected by mutations in either CRTAP or LEPRE1. Proteasomal
      inhibitors partially rescue P3H1 protein in CRTAP-null cells. In LEPRE1-null
      cells, secretion of CRTAP is increased compared with control cells and accounts
      for 15-20% of the decreased CRTAP detected in cells. Thus, mutual stabilization
      of P3H1 and CRTAP in the ER collagen modification complex is an underlying
      mechanism for the overlapping phenotype of types VII and VIII OI.

PMID- 19846467
TI  - Primary cardiac lymphoma: B- and T-cell cases at a specialist UK centre.
AB  - BACKGROUND: Primary cardiac lymphoma is a very rare malignancy, which is
      typically of a non-Hodgkin's type, and involves only the heart and pericardium
      with no or minimal evidence of extracardiac involvement. In the past, they were
      frequently diagnosed at autopsy but modern imaging technology now permits early
      diagnosis and treatment which allows for improved prognosis. PATIENTS AND
      METHODS: This report describes the wide spectrum of clinical presentation,
      difficulty with correct clinical diagnosis, complications of treatment and
      pathologic findings of one of the largest series of primary cardiac lymphomas at
      a specialist UK centre. Our series comprised five males and one female with an
      age range of 10-81 years. RESULTS: Most cases involved at least two chambers with
      the ventricles being the most common site. Clinical presentation included
      arrhythmias, valve incompetence, cardiac failure, pericardial effusion, embolic
      stroke and sudden death. Our study, in contrast to other series, included both B-
      and T-cell lymphomas. CONCLUSIONS: All six cases illustrate the wide spectrum of
      clinical presentation of lymphomas presenting primarily in the heart and
      emphasise that histology of all mass lesions is essential. Other series are small
      like ours highlighting the rarity of these tumours in the heart with the emphasis
      on imaging, early diagnosis and treatment.

PMID- 19846468
TI  - A phase I study to determine the safety, tolerability and maximum tolerated dose
      of green-lipped mussel (Perna canaliculus) lipid extract, in patients with
      advanced prostate and breast cancer.
AB  - BACKGROUND: This was a phase I trial to determine the maximum tolerated dose
      (MTD) of a marine lipid extract from the New Zealand green-lipped mussel (Perna
      canaliculus), as an inhibitor of 5- and 12-lipo-oxygenase enzymes, in patients
      with advanced breast and prostate cancers. PATIENTS AND METHODS: This was an open
      labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel
      lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily
      schedule, orally. Patients remained on study until disease progression or
      unacceptable toxicity. RESULTS: From December 1999 to May 2003, 17 patients were
      enrolled. Fifteen of them were male with advanced prostate cancer and two were
      female with advanced breast cancer. The median age of the patients was 74 years
      (range 56-85 years). Sixteen patients were assessable for adverse events and dose
      limiting toxicity (DLT). Reason for withdrawal from the study included
      progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had
      evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no
      objective tumour responses noted. CONCLUSIONS: GLMLE appears to be a well
      tolerated compound in this setting. There appears to be no objective benefit.
      However, grade 3/4 hepatic toxicity noted in two patients is of concern and
      should be considered while evaluating patients taking GLMLE or while designing
      studies with this agent.

PMID- 19846466
TI  - Murine hippocampal neurons expressing Fmr1 gene premutations show early
      developmental deficits and late degeneration.
AB  - Premutation CGG repeat expansions (55-200 CGG repeats; preCGG) within the fragile
      X mental retardation 1 (FMR1) gene give rise to the neurodegenerative disorder,
      fragile X-associated tremor/ataxia syndrome (FXTAS), primary ovarian
      insufficiency and neurodevelopmental problems. Morphometric analysis of Map2B
      immunofluorescence reveals that neurons cultured from heterozygous female mice
      with preCGG repeats in defined medium display shorter dendritic lengths and fewer
      branches between 7 and 21 days in vitro compared with wild-type (WT) littermates.
      Although the numbers of synapsin and phalloidin puncta do not differ from WT,
      preCGG neurons possess larger puncta. PreCGG neurons display lower viability, and
      express elevated stress protein as they mature. PreCGG neurons have inherently
      different patterns of growth, dendritic complexity and synaptic architecture
      discernable early in the neuronal trajectory to maturation, and may reflect a
      cellular basis for the developmental component of the spectrum of clinical
      involvement in carriers of premutation alleles. The reduced viability of preCGG
      neurons is consistent with the mRNA toxicity and neurodegeneration associated
      with FXTAS.

PMID- 19846469
TI  - Polymorphonuclear leucocytes consume oxygen in sputum from chronic Pseudomonas
      aeruginosa pneumonia in cystic fibrosis.
AB  - BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is the most severe
      complication for patients with cystic fibrosis (CF). This infection is
      characterised by endobronchial mucoid biofilms surrounded by numerous
      polymorphonuclear leucocytes (PMNs). The mucoid phenotype offers protection
      against the PMNs, which are in general assumed to mount an active respiratory
      burst leading to lung tissue deterioration. An ongoing respiratory burst by the
      PMNs has, however, not been demonstrated previously in endobronchial secretions
      from chronically infected patients with CF. OBJECTIVE: Based on the accumulating
      evidence for depletion of molecular oxygen (O(2)) in the mucus in infected CF
      bronchi, it was hypothesised that the O(2) depletion in the mucus in infected CF
      bronchi may be accelerated by the respiratory burst of the PMNs due to the
      reduction of O(2) to the superoxide anion (O(-)(2)) by the phagocyte NADPH
      oxidase (Phox). METHODS: Methods were established to isolate the O(2) consumption
      by the respiratory burst from aerobic respiration in freshly expectorated sputum
      from chronically infected patients with CF. RESULTS: Inhibition of the Phox with
      diphenylene iodonium (DPI) delayed O(2) depletion, nearly abolished staining of
      O(-)(2)-producing PMNs with hydroethidine and inhibited the rapid luminol
      enhanced chemiluminescence in sputum. Furthermore, the total O(2) consumption was
      correlated to the concentration of PMNs in the sputum samples. CONCLUSION: The
      results demonstrate that CF sputum contains PMNs with an active consumption of
      O(2) for O(-)(2) production and suggest that the respiratory burst is ongoing and
      causes accelerated O(2) depletion due to formation of O(-)(2) in the lungs of
      chronically infected patients with CF.

PMID- 19846470
TI  - Spinogenesis and pruning from early visual onset to adulthood: an intracellular
      injection study of layer III pyramidal cells in the ventral visual cortical
      pathway of the macaque monkey.
AB  - Neocortical pyramidal cells are characterized by markedly different structure
      among cortical areas in the mature brain. In the ventral visual pathway of adult
      primates, pyramidal cells become increasingly more branched and more spinous with
      anterior progression through the primary (V1), second (V2), and fourth (V4)
      visual areas and cytoarchitectonic areas TEO and TE. It is not known how these
      regional specializations in neuron structure develop. Here, we report that the
      basal dendritic trees of layer III pyramidal cells in V1, V2, V4, TEO, and TE
      were characterized by unique growth profiles. Different numbers of spines were
      grown in the dendritic trees of cells among these cortical areas and then
      subsequently pruned. In V1, V2, and V4, more spines were pruned than grew
      resulting in a net decrease in the number of spines in the dendritic trees
      following the onset of visual experience. In TEO and TE, neurons grew more spines
      than they pruned from visual onset to adulthood. These data suggest that visual
      experience may influence neuronal maturation in different ways in different
      cortical areas.

PMID- 19846471
TI  - Effect of familial sinistrality on planum temporale surface and brain tissue
      asymmetries.
AB  - The impact of having left-handers (LHs) among one's close relatives, called
      familial sinistrality (FS), on neuroanatomical markers of left-hemisphere
      language specialization was studied in 274 normal adults, including 199 men and
      75 women, among whom 77 men and 27 women were positive for FS. Measurements of
      the surface of a phonological cortical area, the "planum temporale" (PT), and
      gray and white matter hemispheric volumes and asymmetries were made using brain
      magnetic resonance images. The size of the left PT of subjects with left-handed
      close relatives (FS+) was reduced by 10%, decreasing with the number of left
      handed relatives, and lowest when the subject's mother was left-handed. Such
      findings had no counterparts in the right hemisphere, and the subject's
      handedness and sex were found to have no significant effect or interaction with
      FS on the left PT size. The FS+ subjects also exhibited increased gray matter
      volume, reduced hemispheric gray matter leftward asymmetry, and, in LHs, reduced
      strength of hand preference. These results add to the increasing body of evidence
      suggesting multiple and somewhat independent mechanisms for the inheritance of
      hand and language lateralization.

PMID- 19846472
TI  - Neural correlates of the spatial and expectancy components of endogenous and
      stimulus-driven orienting of attention in the Posner task.
AB  - Voluntary orienting of visual attention is conventionally measured in tasks with
      predictive central cues followed by frequent valid targets at the cued location
      and by infrequent invalid targets at the uncued location. This implies that
      invalid targets entail both spatial reorienting of attention and breaching of the
      expected spatial congruency between cues and targets. Here, we used event-related
      functional magnetic resonance imaging (fMRI) to separate the neural correlates of
      the spatial and expectancy components of both endogenous orienting and stimulus
      driven reorienting of attention. We found that during endogenous orienting with
      predictive cues, there was a significant deactivation of the right Temporal
      Parietal Junction (TPJ). We also discovered that the lack of an equivalent
      deactivation with nonpredictive cues was matched to drop in attentional costs and
      preservation of attentional benefits. The right TPJ showed equivalent responses
      to invalid targets following predictive and nonpredictive cues. On the contrary,
      infrequent-unexpected invalid targets following predictive cues specifically
      activated the right Middle and Inferior Frontal Gyrus (MFG-IFG). Additional
      comparisons with spatially neutral trials demonstrated that, independently of cue
      predictiveness, valid targets activate the left TPJ, whereas invalid targets
      activate both the left and right TPJs. These findings show that the selective
      right TPJ activation that is found in the comparison between invalid and valid
      trials results from the reciprocal cancelling of the different activations that
      in the left TPJ are related to the processing of valid and invalid targets. We
      propose that left and right TPJs provide "matching and mismatching to attentional
      template" signals. These signals enable reorienting of attention and play a
      crucial role in the updating of the statistical contingency between cues and
      targets.

PMID- 19846473
TI  - Minnesota's Nursing Facility Performance-Based Incentive Payment Program: an
      innovative model for promoting care quality.
AB  - PURPOSE: Minnesota's Nursing Facility Performance-Based Incentive Payment Program
      (PIPP) supports provider-initiated projects aimed at improving care quality and
      efficiency. PIPP moves beyond conventional pay for performance. It seeks to
      promote implementation of evidence-based practices, encourage innovation and risk
      taking, foster collaboration and shared learning, and establish a solid case for
      investing in better quality from the perspective of the state, providers, and
      consumers. We explain PIPP rationale and design, describe projects and
      participating facilities, and present findings from interviews with project
      leaders. DESIGN AND METHODS: Provider-initiated projects lasting from 1 to 3
      years are selected through a competitive process and are funded for up to 5% of
      the daily operating per diem rate. Providers are at risk of losing up to 20% of
      their project funding if they fail to achieve targets on state nursing facility
      performance measures. RESULTS: Minnesota has made a major investment in the PIPP
      by supporting 45 individual or collaborative projects, representing approximately
      160 facilities and annual funding of approximately $18 million. Projects involve
      a wide range of interventions, such as fall reduction, wound prevention,
      exercise, improved continence, pain management, resident-centered care and
      culture change, and transitions to the community. IMPLICATIONS: The PIPP can
      serve as a model for other states seeking to promote nursing facility quality
      either in combination or in place of conventional pay-for-performance efforts.

PMID- 19846475
TI  - Provision of psychopharmacological services in nursing homes.
AB  - We examined the psychopharmacological services provided within 3 months of
      nursing home (NH) admission to a whole population of newly admitted Florida NH
      residents 65 years and older (N = 947) for a 1-year period via secondary analyses
      of selected variables from Medicaid and the Online Survey and Certification and
      Reporting System. Within 3 months of admission, 12% received
      nonpsychopharmacological mental health care. However, 71% of new residents
      received at least one psychoactive medication, and more than 15% were taking four
      or more psychoactive medications. Most of those being treated with psychoactive
      medication had not received psychopharmacological treatment 6 months prior to
      admission (64%) and had not received a psychiatric diagnosis 6 months preceding
      admission (71%). Blacks were less likely to receive medications than non-Hispanic
      Whites. Results expand on past research by identifying an increase in the amount
      of psychoactive medications prescribed to NH residents, a lack of prior
      psychiatric treatment and diagnoses for those currently receiving psychoactive
      medications, only limited provision of nonpsychopharmacological mental health
      care, and racial or ethnic differences in the use of medications by NHs.

PMID- 19846474
TI  - Does a typical contemplator exist? Three clusters of smokers in contemplation.
AB  - The aim of this study is to test whether subtypes exist among smokers in
      contemplation. Data from 194 adult smokers that participated in a randomized
      controlled trial testing the effectiveness of a computer-tailored smoking
      cessation program in Dutch general practices were used for secondary analysis.
      Cluster analysis was conducted based on baseline scores on pros and cons of
      quitting and self-efficacy to quit. Clusters were cross-sectionally compared for
      demographic variables and smoking characteristics with analyses of variance
      (ANOVA) and Chi-square tests. Logistic and multinomial regression analyses were
      used for longitudinal comparison for smoking behavior and stage of change at 6
      months follow-up. Three clusters were identified: Early, Progressing and
      Disengaged Contemplators. Clusters differed significantly on all clustering
      variables (P < 0.001). Disengaged smokers were significantly less addicted than
      Early Contemplators. Cluster membership was not predictive of outcome measures.
      No subtype was identified representing the Classic Contemplator, scoring high on
      both pros and cons of quitting and low on self-efficacy, as found in previous
      studies among US samples. The predictive validity of the clusters found was
      limited.

PMID- 19846476
TI  - Dominant and recessive inheritance patterns of diapause in the two-spotted spider
      mite Tetranychus urticae.
AB  - In this study, we investigated the diapause incidence in 3 geographic strains of
      the two-spotted spider mite Tetranychus urticae (Acari: Tetranychidae). Under
      diapause-inducing conditions of 12:12 light:dark at 15 degrees C, the diapause
      incidence was nearly 100% in a strain from northern Japan (Sapporo), whereas it
      was nearly 0% in 2 strains from southern Japan (Itoman and Takanabe). Reciprocal
      crosses clearly showed that the nondiapause phenotype is inherited in a
      completely dominant manner, and no maternal effect was detected. Backcrosses to
      the Itoman and Takanabe strains suggested that dominant nondiapause alleles
      control the nondiapause phenotype. To clarify the genetic basis of nondiapause in
      the northern population, we also established a nondiapausing variant ("selected
      nondiapause" abbreviated as snd) from the Sapporo strain. Crossing experiments
      revealed that a single recessive allele is responsible for the nondiapause
      phenotype. Thus, both dominant and recessive inheritance patterns of diapause
      were detected in the T. urticae populations studied here.

PMID- 19846477
TI  - Introduction: symposium on a regulated market in transplantable organs.

PMID- 19846478
TI  - Why should we compensate organ donors when we can continue to take organs for
      free? A response to some of my critics.
AB  - In Kidney for Sale by Owner: Human Organs, Transplantation, and the Market, I
      argued that the market is the most efficient and effective-and morally justified
      means of procuring and allocating human organs for transplantation. This special
      issue of The Journal of Medicine and Philosophy publishes several articles
      critical of this position and of my arguments mustered in its support. In this
      essay, I explore the core criticisms these authors raise against my conclusions.
      I argue that clinging to comfortable, but unfounded, notions that human body
      parts are not commodities, that the physician-patient relationship transcends
      commercial practices, and that medicine rises above market-place morality (where
      "market-place morality" is presented rhetorically as a criticism) leads to a real
      failure adequately to appreciate the complex reality of modern medicine. Denying
      the illicit moral intuitions that commodification of body parts is immoral or
      that it necessarily violates human dignity would benefit donors and recipients
      alike, while also reinforcing virtuous transplantation practice and policy.
      Honestly acknowledging the medical marketplace would shed light on what is often
      a hazy and shrouded policy setting. At stake is not solely the efficiency of
      procuring human organs for transplantation but also the recognition of the moral
      authority of persons over themselves.

PMID- 19846479
TI  - Autonomy, moral constraints, and markets in kidneys.
AB  - This article concerns the morality of establishing regulated kidney markets in an
      effort to reduce the chronic shortage of kidneys for transplant. The article
      tries to rebut the view, recently defended by James Taylor, that if we hold
      autonomy to be intrinsically valuable, then we should be in favor of such
      markets. The article then argues that, under current conditions, the buying and
      selling of organs in regulated markets would sometimes violate two Kantian
      principles that are seen as moral constraints. One principle forbids expressing
      disrespect for the dignity of humanity; the other forbids treating others merely
      as means. In light of the moral danger posed by regulated markets, the article
      advocates an alternative way of diminishing the current organ shortage, namely
      opt-out systems of cadaveric organ donation.

PMID- 19846480
TI  - Seizures in a 9 month old girl.

PMID- 19846483
TI  - Zona pellucida protein ZP2 is expressed in the oocyte of Japanese quail (Coturnix
      japonica).
AB  - The avian perivitelline layer (PL), a vestment homologous to the zona pellucida
      (ZP) of mammalian oocytes, is composed of at least three glycoproteins. Our
      previous studies have demonstrated that the matrix's components, ZP3 and ZPD, are
      synthesized in ovarian granulosa cells. Another component, ZP1, is synthesized in
      the liver and is transported to the ovary by blood circulation. In this study, we
      report the isolation of cDNA encoding quail ZP2 and its expression in the female
      bird. By RNase protection assay and in situ hybridization, we demonstrate that
      ZP2 transcripts are restricted to the oocytes of small white follicles (SWF). The
      expression level of ZP2 decreased dramatically during follicular development, and
      the highest expression was observed in the SWF. Western blot and
      immunohistochemical analyses using the specific antibody against ZP2 indicate
      that the 80 kDa protein is the authentic ZP2, and the immunoreactive ZP2 protein
      is also present in the oocytes. Moreover, ultrastructural analysis demonstrated
      that the immunoreactive ZP2 localizes to the zona radiata, the perivitelline
      space, and the oocyte cytoplasm in the SWF. By means of western blot analysis and
      immunofluorescence microscopy, we detected a possible interaction of the
      recombinant ZP2 with ZP3 and that this interaction might lead to the formation of
      amorphous structure on the cell surface. These results demonstrate for the first
      time that the avian ZP gene is expressed in the oocyte, and that the ZP2 protein
      in the oocyte might play a role for the PL formation in the immature follicles of
      the ovary.

PMID- 19846484
TI  - Differences in oocyte development and estradiol sensitivity among mouse strains.
AB  - Mouse oocytes develop in clusters of interconnected cells called germline cysts.
      Shortly after birth, the majority of cysts break apart and primordial follicles
      form, consisting of one oocyte surrounded by granulosa cells. Concurrently,
      oocyte number is reduced by two-thirds. Exposure of neonatal females to
      estrogenic compounds causes multiple oocyte follicles that are likely germline
      cysts that did not break down. Supporting this idea, estrogen disrupts cyst
      breakdown and may regulate normal oocyte development. Previously, the CD-1 strain
      was used to study cyst breakdown and oocyte survival, but it is unknown if there
      are differences in these processes in other mouse strains. It is also unknown if
      there are variations in estrogen sensitivity during oocyte development. Here, we
      examined neonatal oocyte development in FVB, C57BL/6, and F2 hybrid (Oct4-GFP)
      strains, and compared them with the CD-1 strain. We found variability in oocyte
      development among the four strains. We also investigated estrogen sensitivity
      differences, and found that C57BL/6 ovaries are more sensitive to estradiol than
      CD-1, FVB, or Oct4-GFP ovaries. Insight into differences in oocyte development
      will facilitate comparison of mice generated on different genetic backgrounds.
      Understanding variations in estrogen sensitivity will lead to better
      understanding of the risks of environmental estrogen exposure in humans.

PMID- 19846485
TI  - Effect of FSH on testicular morphology and spermatogenesis in gonadotrophin
      deficient hypogonadal mice lacking androgen receptors.
AB  - FSH and androgen act to stimulate and maintain spermatogenesis. FSH acts directly
      on the Sertoli cells to stimulate germ cell number and acts indirectly to
      increase androgen production by the Leydig cells. In order to differentiate
      between the direct effects of FSH on spermatogenesis and those mediated
      indirectly through androgen action, we have crossed hypogonadal (hpg) mice, which
      lack gonadotrophins, with mice lacking androgen receptors (AR) either
      ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO
      and hpg.SCARKO mice were treated with recombinant FSH for 7 days and testicular
      morphology and cell numbers were assessed. In untreated hpg and hpg.SCARKO mice,
      germ cell development was limited and did not progress beyond the pachytene
      stage. In hpg.ARKO mice, testes were smaller with fewer Sertoli cells and germ
      cells compared to hpg mice. Treatment with FSH had no effect on Sertoli cell
      number but significantly increased germ cell numbers in all groups. In hpg mice,
      FSH increased the numbers of spermatogonia and spermatocytes, and induced round
      spermatid formation. In hpg.SCARKO and hpg.ARKO mice, in contrast, only
      spermatogonial and spermatocyte numbers were increased with no formation of
      spermatids. Leydig cell numbers were increased by FSH in hpg and hpg.SCARKO mice
      but not in hpg.ARKO mice. Results show that in rodents 1) FSH acts to stimulate
      spermatogenesis through an increase in spermatogonial number and subsequent entry
      of these cells into meiosis, 2) FSH has no direct effect on the completion of
      meiosis and 3) FSH effects on Leydig cell number are mediated through
      interstitial ARs.

PMID- 19846486
TI  - Thighs and heart disease. Thighs and thresholds.

PMID- 19846487
TI  - Thighs and heart disease. Exercise, muscle mass, and insulin sensitivity.

PMID- 19846489
TI  - Equity and NHS reforms. What about independent sector treatment centres?

PMID- 19846490
TI  - Tom MacDonald replies to Marisa de Andrade.

PMID- 19846491
TI  - Capsule endoscopy. Technique has limitations.

PMID- 19846492
TI  - Prostate specific antigen. Prostate screening in France.

PMID- 19846493
TI  - SSRIs and congenital defects. Case registers in pregnancy?

PMID- 19846494
TI  - SSRIs and heart defects in neonates.

PMID- 19846495
TI  - Women should give informed consent before starting SSRIs.

PMID- 19846496
TI  - SSRIs and congenital defects. Spontaneous publishing and academic miscarriages
      (SPAM).

PMID- 19846497
TI  - Global agreement needed to prevent trafficking in organs, says UN and Council of
      Europe.

PMID- 19846501
TI  - Only 12% of Germans say they will have H1N1 vaccine after row blows up over
      safety of adjuvants.

PMID- 19846506
TI  - Record number of infants immunised but 24 million in poor nations not being
      reached, says report.

PMID- 19846508
TI  - 17-beta estradiol promotion of herpes simplex virus type 1 reactivation is
      estrogen receptor dependent.
AB  - Correlations between estrogen and herpes simplex virus (HSV) reactivation from
      latency have been suggested by numerous clinical reports, but causal associations
      are not well delineated. In a murine HSV-1 corneal infection model, we establish
      17-beta estradiol (17-betaE) treatment of latently infected ovariectomized mice
      induces viral reactivation, as demonstrated by increased viral load and increased
      immediate-early viral gene expression in the latently infected trigeminal ganglia
      (TG). Interestingly, the increased HSV reactivation occurred in the absence of
      inhibition of viral specific CD8(+) T-cell effector function. 17-betaE
      administration increased HSV reactivation in CD45(+) cell-depleted TG explant
      cultures, providing further support that leukocyte-independent effects on
      latently infected neurons were responsible for the increased reactivation. The
      drug-induced increases in HSV copy number were not recapitulated upon in vivo
      treatment of latently infected estrogen receptor alpha-deficient mice, evidence
      that HSV reactivation promoted by 17-betaE was estrogen receptor dependent. These
      findings provide additional framework for the emerging conceptualization of HSV
      latency as a dynamic process maintained by complex interactions among multiple
      cooperative and competing host, viral, and environmental forces. Additional
      research is needed to confirm whether pregnancy or hormonal contraceptives
      containing 17-betaE also promote HSV reactivation from latency in an estrogen
      receptor-dependent manner.

PMID- 19846507
TI  - Targeting the proteolytic processing of the viral glycoprotein precursor is a
      promising novel antiviral strategy against arenaviruses.
AB  - A crucial step in the arenavirus life cycle is the biosynthesis of the viral
      envelope glycoprotein (GP) responsible for virus attachment and entry. Processing
      of the GP precursor (GPC) by the cellular proprotein convertase site 1 protease
      (S1P), also known as subtilisin-kexin-isozyme 1 (SKI-1), is crucial for cell-to
      cell propagation of infection and production of infectious virus. Here, we sought
      to evaluate arenavirus GPC processing by S1P as a target for antiviral therapy
      using a recently developed peptide-based S1P inhibitor, decanoyl (dec)-RRLL
      chloromethylketone (CMK), and the prototypic arenavirus lymphocytic
      choriomeningitis virus (LCMV). To control for off-target effects of dec-RRLL-CMK,
      we employed arenavirus reverse genetics to introduce a furin recognition site
      into the GPC of LCMV. The rescued mutant virus grew to normal titers, and the
      processing of its GPC critically depended on cellular furin, but not S1P.
      Treatment with the S1P inhibitor dec-RRLL-CMK resulted in specific blocking of
      viral spread and virus production of LCMV. Combination of the protease inhibitor
      with ribavirin, currently used clinically for treatment of human arenavirus
      infections, resulted in additive drug effects. In cells deficient in S1P, the
      furin-dependent LCMV variant established persistent infection, whereas wild-type
      LCMV underwent extinction without the emergence of S1P-independent escape
      variants. Together, the potent antiviral activity of an inhibitor of S1P
      dependent GPC cleavage, the additive antiviral effect with ribavirin, and the low
      probability of emergence of S1P-independent viral escape variants make S1P
      mediated GPC processing by peptide-derived inhibitors a promising strategy for
      the development of novel antiarenaviral drugs.

PMID- 19846509
TI  - Interaction of the betapapillomavirus E2 tethering protein with mitotic
      chromosomes.
AB  - During persistent papillomavirus infection, the viral E2 protein tethers the
      viral genome to the host cell chromosomes, ensuring maintenance and segregation
      of the viral genome during cell division. However, E2 proteins from different
      papillomaviruses interact with distinct chromosomal regions and targets. The
      tethering mechanism has been best characterized for bovine papillomavirus type 1
      (BPV1), where the E2 protein tethers the viral genome to mitotic chromosomes in
      complex with the cellular bromodomain protein, Brd4. In contrast, the
      betapapillomavirus human papillomavirus type 8 (HPV8) E2 protein binds to the
      repeated ribosomal DNA genes that are found on the short arm of human acrocentric
      chromosomes. In this study, we show that a short 16-amino-acid peptide from the
      hinge region and the C-terminal DNA binding domain of HPV8 E2 are necessary and
      sufficient for interaction with mitotic chromosomes. This 16-amino-acid region
      contains an RXXS motif that is highly conserved among betapapillomaviruses, and
      both arginine 250 and serine 253 residues within this motif are required for
      mitotic chromosome binding. The HPV8 E2 proteins are highly phosphorylated, and
      serine 253 is a site of phosphorylation. The HPV8 E2 chromosome binding sequence
      also has sequence similarity with chromosome binding regions in the
      gammaherpesvirus EBNA and LANA tethering proteins.

PMID- 19846510
TI  - Associations between HLA class I alleles and escape mutations in the hepatitis B
      virus core gene in New Zealand-resident Tongans.
AB  - The full repertoire of hepatitis B virus (HBV) peptides that bind to the common
      HLA class I molecules found in areas with a high prevalence of chronic HBV
      infection has not been determined. This information may be useful for designing
      immunotherapies for chronic hepatitis B. We identified amino acid residues under
      positive selection pressure in the HBV core gene by phylogenetic analysis of
      cloned DNA sequences obtained from HBV DNA extracted from the sera of Tongan
      subjects with inactive, HBeAg-negative chronic HBV infections. The repertoires of
      positively selected sites in groups of subjects who were homozygous for either
      HLA-B*4001 (n = 10) or HLA-B*5602 (n = 7) were compared. We identified 13 amino
      acid sites under positive selection pressure. A significant association between
      an HLA class I allele and the presence of nonsynonymous mutations was found at
      five of these sites. HLA-B*4001 was associated with mutations at E77 (P = 0.05)
      and E113 (P = 0.002), and HLA-B*5602 was associated with mutations at S21 (P =
      0.02). In addition, amino acid mutations at V13 (P = 0.03) and E14 (P = 0.01)
      were more common in the seven subjects with an HLA-A*02 allele. In summary, we
      have developed an assay that can identify associations between HLA class I
      alleles and HBV core gene amino acids that mutate in response to selection
      pressure. This is consistent with published evidence that CD8(+) T cells have a
      role in suppressing viral replication in inactive, HBeAg-negative chronic HBV
      infection. This assay may be useful for identifying the clinically significant
      HBV peptides that bind to common HLA class I molecules.

PMID- 19846511
TI  - Human cytomegalovirus induces the interferon response via the DNA sensor ZBP1.
AB  - Human cytomegalovirus (HCMV) is a member of the betaherpesvirus family that,
      unlike other herpesviruses, triggers a strong innate immune response in infected
      cells that includes transcription of the beta interferon gene via activation of
      interferon regulatory factor 3 (IRF3). IRF3 activation requires signaling from
      pattern recognition receptors that is initiated by their interaction with
      specific pathogen-associated molecules. However, while IRF3-activating pathways
      are increasingly well characterized, the cellular molecules involved in HCMV
      mediated IRF3-dependent beta interferon transcription are virtually unknown. We
      undertook a systematic examination of new and established IRF3-terminal pathway
      components to identify those that are essential to HCMV-triggered IRF3
      activation. We show here that IRF3 activation induced by HCMV infection involves
      the newly identified protein STING but, in contrast to infections with other
      herpesviruses, occurs independently of the adaptor molecule IPS-1. We also show
      that the protein DDX3 contributes to HCMV-triggered expression of beta
      interferon. Moreover, we identify Z-DNA binding protein 1 (ZBP1) as being
      essential for IRF3 activation and interferon beta expression triggered by HCMV,
      as well as being sufficient to enhance HCMV-stimulated beta interferon
      transcription and secretion. ZBP1 transcription was also found to be induced
      following exposure to HCMV in a JAK/STAT-dependent manner, thus perhaps also
      contributing to a positive feedback signal. Finally, we show that constitutive
      overexpression of ZBP1 inhibits HCMV replication. ZBP1 was recently identified as
      a cytosolic pattern recognition receptor of double-stranded DNA, and thus, we
      propose a model for HCMV-mediated IRF3 activation that involves HCMV-associated
      DNA as the principal innate immune-activating pathogen-associated molecular
      pattern.

PMID- 19846512
TI  - Differential specificity and immunogenicity of adenovirus type 5 neutralizing
      antibodies elicited by natural infection or immunization.
AB  - A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant
      adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and
      was associated with increased risk of human immunodeficiency virus type 1 (HIV-1)
      infection. Preexisting immunity to Ad5 in humans could therefore affect both
      immunogenicity and vaccine efficacy. We hypothesized that vaccine-induced
      immunity is differentially affected, depending on whether subjects were exposed
      to Ad5 by natural infection or by vaccination. Serum samples from vaccine trial
      subjects receiving a DNA/rAd5 AIDS vaccine with or without prior immunity to Ad5
      were examined for the specificity of their Ad5 neutralizing antibodies and their
      effect on HIV-1 immune responses. Here, we report that rAd5 neutralizing
      antibodies were directed to different components of the virion, depending on
      whether they were elicited by natural infection or vaccination in HIV vaccine
      trial subjects. Neutralizing antibodies elicited by natural infection were
      directed largely to the Ad5 fiber, while exposure to rAd5 through vaccination
      elicited antibodies primarily to capsid proteins other than fiber. Notably,
      preexisting immunity to Ad5 fiber from natural infection significantly reduced
      the CD4 and CD8 cell responses to HIV Gag after DNA/rAd5 vaccination. The
      specificity of Ad5 neutralizing antibodies therefore differs depending on the
      route of exposure, and natural Ad5 infection compromises Ad5 vaccine-induced
      immunity to weak immunogens, such as HIV-1 Gag. These results have implications
      for future AIDS vaccine trials and the design of next-generation gene-based
      vaccine vectors.

PMID- 19846513
TI  - Hepatitis B virus requires intact caveolin-1 function for productive infection in
      HepaRG cells.
AB  - Investigation of the entry pathways of hepatitis B virus (HBV), a member of the
      family Hepadnaviridae, has been hampered by the lack of versatile in vitro
      infectivity models. Most concepts of hepadnaviral infection come from the more
      robust duck HBV system; however, whether the two viruses use the same mechanisms
      to invade target cells is still a matter of controversy. In this study, we
      investigate the role of an important plasma membrane component, caveolin-1 (Cav
      1), in HBV infection. Caveolins are the main structural components of caveolae,
      plasma membrane microdomains enriched in cholesterol and sphingolipids, which are
      involved in the endocytosis of numerous ligands and complex signaling pathways
      within the cell. We used the HepaRG cell line permissive for HBV infection to
      stably express dominant-negative Cav-1 and dynamin-2, a GTPase involved in
      vesicle formation at the plasma membrane and other organelles. The endocytic
      properties of the newly established cell lines, designated HepaRG(Cav-1),
      HepaRG(Cav-1Delta1-81), HepaRG(Dyn-2), and HepaRG(Dyn-2K44A), were validated
      using specific markers for different entry routes. The cells maintained their
      properties during cell culture, supported differentiation, and were permissive
      for HBV infection. The levels of both HBV transcripts and antigens were
      significantly decreased in cells expressing the mutant proteins, while viral
      replication was not directly affected. Chemical inhibitors that specifically
      inhibit clathrin-mediated endocytosis had no effect on HBV infection. We
      concluded that HBV requires a Cav-1-mediated entry pathway to initiate productive
      infection in HepaRG cells.

PMID- 19846514
TI  - Role of a putative gp41 dimerization domain in human immunodeficiency virus type
      1 membrane fusion.
AB  - The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell
      entails a series of conformational changes in the gp41 transmembrane glycoprotein
      that mediates the fusion of the viral and target cell membranes. A trimer-of
      hairpins structure formed by the association of two heptad repeat (HR) regions of
      the gp41 ectodomain has been implicated in a late step of the fusion pathway.
      Earlier native and intermediate states of the protein are postulated to mediate
      the antiviral activity of the fusion inhibitor enfuvirtide and of broadly
      neutralizing monoclonal antibodies (NAbs), but the details of these structures
      remain unknown. Here, we report the identification and crystal structure of a
      dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or
      C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil
      with two distinct C-terminal alpha-helical overhangs. This dimer structure is
      conferred largely by interactions within a central core that corresponds to the
      sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely
      impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure
      binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential
      intermediate conformation of gp41. These results should enhance our understanding
      of the molecular basis of the gp41 fusogenic structural transitions and thereby
      guide rational, structure-based efforts to design new fusion inhibitors and
      vaccine candidates intended to induce broadly neutralizing antibodies.

PMID- 19846515
TI  - Different tempo and anatomic location of dual-tropic and X4 virus emergence in a
      model of R5 simian-human immunodeficiency virus infection.
AB  - We previously reported coreceptor switch in rhesus macaques inoculated
      intravenously with R5 simian-human immunodeficiency virus SF162P3N
      (SHIV(SF162P3N)). Whether R5-to-X4 virus evolution occurs in mucosally infected
      animals and in which anatomic site the switch occurs, however, were not
      addressed. We herein report a change in coreceptor preference in macaques
      infected intrarectally with SHIV(SF162P3N). The switch occurred in infected
      animals with high levels of virus replication and undetectable antiviral antibody
      response and required sequence changes in the V3 loop of the gp120 envelope
      protein. X4 virus emergence was associated with an accelerated drop in peripheral
      CD4(+) T-cell count but followed rather than preceded the onset of CD4(+) T-cell
      loss. The conditions, genotypic requirements, and patterns of coreceptor switch
      in intrarectally infected animals were thus remarkably consistent with those
      found in macaques infected intravenously. They also overlapped with those
      reported for humans, suggestive of a common mechanism for coreceptor switch in
      the two hosts. Furthermore, two independent R5-to-X4 evolutionary pathways were
      identified in one infected animal, giving rise to dual-tropic and X4 viruses
      which differed in switch kinetics and tissue localization. The dual-tropic switch
      event predominated early, and the virus established infection in multiple tissues
      sites. In contrast, the switch to X4 virus occurred later, initiating and
      expanding mainly in peripheral lymph nodes. These findings help define R5
      SHIV(SF162P3N) infection of rhesus macaques as a model to study the mechanistic
      basis, dynamics, and sites of HIV-1 coreceptor switch.

PMID- 19846516
TI  - Human cytomegalovirus gene UL21a encodes a short-lived cytoplasmic protein and
      facilitates virus replication in fibroblasts.
AB  - The human cytomegalovirus (HCMV) gene UL21a was recently annotated by its
      conservation in chimpanzee cytomegalovirus. Two large-scale mutagenic analyses
      showed that mutations in overlapping UL21a/UL21 resulted in a severe defect of
      virus growth in fibroblasts. Here, we characterized UL21a and demonstrated its
      role in HCMV infection. We mapped a UL21a-specific transcript of approximately
      600 bp that was expressed with early kinetics. UL21a encoded pUL21a, a protein of
      approximately 15 kDa, which was unstable and localized predominantly to the
      cytoplasm during HCMV infection or when expressed alone. Interestingly, pUL21a
      was drastically stabilized in the presence of proteasome inhibitor MG132, but its
      instability was independent of a functional ubiquitin-mediated pathway,
      suggesting that pUL21a underwent proteasome-dependent, ubiquitin-independent
      degradation. A UL21a deletion virus was attenuated in primary human newborn
      foreskin fibroblasts (HFFs) and embryonic lung fibroblasts (MRC-5), whereas a
      marker-rescued virus and mutant viruses lacking the neighboring or overlapping
      genes UL20, UL21, or UL21.5-UL23 replicated at wild-type levels. The growth
      defect of UL21a-deficient virus in MRC-5 cells was more pronounced than that in
      HFFs. At a high multiplicity of infection, the UL21a deletion virus synthesized
      viral proteins with wild-type kinetics but had a two- to threefold defect in
      viral DNA replication. More importantly, although pUL21a was not detected in the
      virion, progeny virions produced by the mutant virus were approximately 10 times
      less infectious than wild-type virus, suggesting that UL21a is required for HCMV
      to establish efficient productive infection. We conclude that UL21a encodes a
      short-lived cytoplasmic protein and facilitates HCMV replication in fibroblasts.

PMID- 19846517
TI  - Mechanisms of protein kinase PKR-mediated amplification of beta interferon
      induction by C protein-deficient measles virus.
AB  - The measles virus P gene products V and C antagonize the host interferon (IFN)
      response, blocking both IFN signaling and production. Using Moraten vaccine
      strain-derived measles virus and isogenic mutants deficient for either V or C
      protein production (V(ko) and C(ko), respectively), we observed that the C(ko)
      virus was a potent inducer of IFN-beta, while induction by V(ko) virus was an
      order of magnitude lower than that by the C(ko) virus. The parental recombinant
      Moraten virus did not significantly induce IFN-beta. The enhanced IFN-inducing
      capacity of the C(ko) virus correlated with an enhanced activation of IFN
      regulatory factor 3 (IRF-3), NF-kappaB, and ATF-2 in C(ko)-infected compared to
      V(ko) or parental virus-infected cells. Furthermore, protein kinase PKR and
      mitochondrial adapter IPS-1 were required for maximal C(ko)-mediated IFN-beta
      induction, which correlated with the PKR-mediated enhancement of mitogen
      activated protein kinase and NF-kappaB activation. Our results reveal multiple
      consequences of C protein expression and document an important function for PKR
      as an enhancer of IFN-beta induction during measles virus infection.

PMID- 19846518
TI  - Effects of phosphorylation of herpes simplex virus 1 envelope glycoprotein B by
      Us3 kinase in vivo and in vitro.
AB  - We recently reported that the herpes simplex virus 1 (HSV-1) Us3 protein kinase
      phosphorylates threonine at position 887 (Thr-887) in the cytoplasmic tail of
      envelope glycoprotein B (gB) (A. Kato, J. Arii, I. Shiratori, H. Akashi, H.
      Arase, and Y. Kawaguchi, J. Virol. 83:250-261, 2009; T. Wisner, C. C. Wright, A.
      Kato, Y. Kawaguchi, F. Mou, J. D. Baines, R. J. Roller and D. C. Johnson, J.
      Virol. 83:3115-3126, 2009). In the studies reported here, we examined the
      effect(s) of this phosphorylation on viral replication and pathogenesis in vivo
      and present data showing that replacement of gB Thr-887 by alanine significantly
      reduced viral replication in the mouse cornea and development of herpes stroma
      keratitis and periocular skin disease in mice. The same effects have been
      reported for mice infected with a recombinant HSV-1 carrying a kinase-inactive
      mutant of Us3. These observations suggested that Us3 phosphorylation of gB Thr
      887 played a critical role in viral replication in vivo and in HSV-1
      pathogenesis. In addition, we generated a monoclonal antibody that specifically
      reacted with phosphorylated gB Thr-887 and used this antibody to show that Us3
      phosphorylation of gB Thr-887 regulated subcellular localization of gB,
      particularly on the cell surface of infected cells.

PMID- 19846519
TI  - The requirement for cellular transportin 3 (TNPO3 or TRN-SR2) during infection
      maps to human immunodeficiency virus type 1 capsid and not integrase.
AB  - Recent genome-wide screens have highlighted an important role for transportin 3
      in human immunodeficiency virus type 1 (HIV-1) infection and preintegration
      complex (PIC) nuclear import. Moreover, HIV-1 integrase interacted with
      recombinant transportin 3 protein under conditions whereby Moloney murine
      leukemia virus (MLV) integrase failed to do so, suggesting that integrase
      transportin 3 interactions might underscore active retroviral PIC nuclear import.
      Here we correlate infectivity defects in transportin 3 knockdown cells with in
      vitro protein binding affinities for an expanded set of retroviruses that include
      simian immunodeficiency virus (SIV), bovine immunodeficiency virus (BIV), equine
      infectious anemia virus (EIAV), feline immunodeficiency virus (FIV), and Rous
      sarcoma virus (RSV) to critically address the role of integrase-transportin 3
      interactions in viral infection. Lentiviruses, with the exception of FIV, display
      a requirement for transportin 3 in comparison to MLV and RSV, yielding an
      infection-based dependency ranking of SIV > HIV-1 > BIV and EIAV > MLV, RSV, and
      FIV. In vitro pulldown and surface plasmon resonance assays, in contrast, define
      a notably different integrase-transportin 3 binding hierarchy: FIV, HIV-1, and
      BIV > SIV and MLV > EIAV. Our results therefore fail to support a critical role
      for integrase binding in dictating transportin 3 dependency during retrovirus
      infection. In addition to integrase, capsid has been highlighted as a retroviral
      nuclear import determinant. Accordingly, MLV/HIV-1 chimera viruses pinpoint the
      genetic determinant of sensitization to transportin 3 knockdown to the HIV-1
      capsid protein. We therefore conclude that capsid, not integrase, is the dominant
      viral factor that dictates transportin 3 dependency during HIV-1 infection.

PMID- 19846520
TI  - Functional analysis of a cellular microRNA in insect host-ascovirus interaction.
AB  - MicroRNAs (miRNAs) have emerged as key regulators in many biological processes,
      from development to defense, at almost all organismal levels. Recently, their
      role has been highlighted in pathogen-host interactions. Emerging evidence from a
      variety of virus-host systems indicates that cellular as well as virally encoded
      miRNAs influence viral replication. Here, we report changes in expression levels
      of host miRNAs upon ascovirus infection in an insect cell line and investigated
      the role of a host miRNA, Hz-miR24, in the host-virus system. We found that Hz
      miR24 is differentially expressed following virus infection, with an increase in
      its expression levels late in infection. Experimental evidence demonstrated that
      Hz-miR24 downregulates ascoviral DNA-dependent RNA polymerase and its beta
      subunit transcript levels late in infection. The specific miRNA-target
      interactions were investigated and confirmed using the ectopic expression of Hz
      miR24 and a green fluorescent protein-based reporter system. Further, the
      expression of the target gene was substantially enhanced in cells transfected
      with a synthesized inhibitor of Hz-miR24. These findings suggest that ascoviruses
      manipulate host miRNAs that in turn regulate the expression of their genes at
      specific time points after infection. To our knowledge, this is the first
      cellular miRNA reported to interact with an insect virus.

PMID- 19846521
TI  - Pathogenesis of hepatitis C virus infection in Tupaia belangeri.
AB  - The lack of a small-animal model has hampered the analysis of hepatitis C virus
      (HCV) pathogenesis. The tupaia (Tupaia belangeri), a tree shrew, has shown
      susceptibility to HCV infection and has been considered a possible candidate for
      a small experimental model of HCV infection. However, a longitudinal analysis of
      HCV-infected tupaias has yet to be described. Here, we provide an analysis of HCV
      pathogenesis during the course of infection in tupaias over a 3-year period. The
      animals were inoculated with hepatitis C patient serum HCR6 or viral particles
      reconstituted from full-length cDNA. In either case, inoculation caused mild
      hepatitis and intermittent viremia during the acute phase of infection.
      Histological analysis of infected livers revealed that HCV caused chronic
      hepatitis that worsened in a time-dependent manner. Liver steatosis, cirrhotic
      nodules, and accompanying tumorigenesis were also detected. To examine whether
      infectious virus particles were produced in tupaia livers, naive animals were
      inoculated with sera from HCV-infected tupaias, which had been confirmed positive
      for HCV RNA. As a result, the recipient animals also displayed mild hepatitis and
      intermittent viremia. Quasispecies were also observed in the NS5A region,
      signaling phylogenic lineage from the original inoculating sequence. Taken
      together, these data suggest that the tupaia is a practical animal model for
      experimental studies of HCV infection.

PMID- 19846522
TI  - Both RIG-I and MDA5 RNA helicases contribute to the induction of alpha/beta
      interferon in measles virus-infected human cells.
AB  - Measles virus (MV), a member of the family Paramyxoviridae, is a nonsegmented
      negative-strand RNA virus. The RNA helicases retinoic acid-inducible gene I (RIG
      I) and melanoma differentiation-associated gene 5 (MDA5) are differentially
      involved in the detection of cytoplasmic viral RNAs and induction of alpha/beta
      interferon (IFN-alpha/beta). RIG-I is generally believed to play a major role in
      the recognition of paramyxoviruses, whereas many viruses of this family produce V
      proteins that can inhibit MDA5. To determine the individual roles of MDA5 and RIG
      I in IFN induction after MV infection, small interfering RNA-mediated knockdown
      of MDA5 or RIG-I was performed in the human epithelial cell line H358, which is
      susceptible to wild-type MV isolates. The production of IFN-beta mRNA in response
      to MV infection was greatly reduced in RIG-I knockdown clones compared to that in
      H358 cells, confirming the importance of RIG-I in the detection of MV. The IFN
      beta mRNA levels were also moderately reduced in MDA5 knockdown clones, even
      though these clones retained fully functional RIG-I. A V protein-deficient
      recombinant MV (MVDeltaV) induced higher amounts of IFN-beta mRNA at the early
      stage of infection in H358 cells compared to the parental virus. The reductions
      in the IFN-beta mRNA levels in RIG-I knockdown clones were less pronounced after
      infection with MVDeltaV than after infection with the parental virus. Taken
      together, the present results indicate that RIG-I and MDA5 both contribute to the
      recognition of MV and that the V protein promotes MV growth at least partly by
      inhibiting the MDA5-mediated IFN responses.

PMID- 19846523
TI  - Modulation of hepatitis C virus RNA abundance and the isoprenoid biosynthesis
      pathway by microRNA miR-122 involves distinct mechanisms.
AB  - MicroRNA 122 (miR-122) promotes hepatitis C virus (HCV) RNA abundance through a
      direct interaction with the viral RNA and stimulates the mevalonate pathway in
      the animal liver. We found that overexpression of miR-122 enhanced viral RNA
      accumulation without affecting genes in the mevalonate pathway, such as the 3
      hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene. However, inhibition
      of miR-122 decreased both HCV RNA and HMGCR RNA with little effects on the rates
      of HCV and HMGCR RNA synthesis. Loss of HCV RNA could not be restored by
      isoprenoid intermediate metabolites. Overall, these findings suggest that miR-122
      modulates viral RNA abundance independently of its effect on isoprenoid
      metabolism.

PMID- 19846524
TI  - The rubella virus capsid protein inhibits mitochondrial import.
AB  - The rubella virus (RV) capsid is an RNA-binding protein that functions in
      nucleocapsid assembly at the Golgi complex, the site of virus budding. In
      addition to its role in virus assembly, pools of capsid associate with
      mitochondria, a localization that is not consistent with virus assembly. Here we
      examined the interaction of capsid with mitochondria and showed that this viral
      protein inhibits the import and processing of mitochondrial precursor proteins in
      vitro. Moreover, RV-infected cells were found to contain lower intramitochondrial
      levels of matrix protein p32. In addition to inhibiting the translocation of
      substrates into mammalian mitochondria, capsid efficiently blocked import into
      yeast mitochondria, thereby suggesting that it acts by targeting a highly
      conserved component of the translocation apparatus. Finally, mutation of a
      cluster of five arginine residues in the amino terminus of capsid, though not
      interfering with its binding to mitochondria, abrogated its ability to block
      protein import into mitochondria. This is the first report of a viral protein
      that affects the import of proteins into mitochondria.

PMID- 19846525
TI  - Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible
      factor 1 alpha-mediated glycolytic adaptation.
AB  - Hepatitis C virus (HCV) infection induces a state of oxidative stress by
      affecting mitochondrial-respiratory-chain activity. By using cell lines inducibly
      expressing different HCV constructs, we showed previously that viral-protein
      expression leads to severe impairment of mitochondrial oxidative phosphorylation
      and to major reliance on nonoxidative glucose metabolism. However, the
      bioenergetic competence of the induced cells was not compromised, indicating an
      efficient prosurvival adaptive response. Here, we show that HCV protein
      expression activates hypoxia-inducible factor 1 (HIF-1) by normoxic stabilization
      of its alpha subunit. In consequence, expression of HIF-controlled genes,
      including those coding for glycolytic enzymes, was significantly upregulated.
      Similar expression of HIF-controlled genes was observed in cell lines inducibly
      expressing subgenomic HCV constructs encoding either structural or nonstructural
      viral proteins. Stabilization and transcriptional activation of HIF-1alpha was
      confirmed in Huh-7.5 cells harboring cell culture-derived infectious HCV and in
      liver biopsy specimens from patients with chronic hepatitis C. The HCV-related
      HIF-1alpha stabilization was insensitive to antioxidant treatment. Mimicking an
      impairment of mitochondrial oxidative phosphorylation by treatment of inducible
      cell lines with oligomycin resulted in stabilization of HIF-1alpha. Similar
      results were obtained by treatment with pyruvate, indicating that accumulation of
      intermediate metabolites is sufficient to stabilize HIF-1alpha. These
      observations provide new insights into the pathogenesis of chronic hepatitis C
      and, possibly, the HCV-related development of hepatocellular carcinoma.

PMID- 19846526
TI  - Murine hepatitis virus nonstructural protein 4 regulates virus-induced membrane
      modifications and replication complex function.
AB  - Positive-strand RNA viruses induce modifications of cytoplasmic membranes to form
      replication complexes. For coronaviruses, replicase nonstructural protein 4
      (nsp4) has been proposed to function in the formation and organization of
      replication complexes. Murine hepatitis virus (MHV) nsp4 is glycosylated at
      residues Asn176 (N176) and N237 during plasmid expression of nsp4 in cells. To
      test if MHV nsp4 residues N176 and N237 are glycosylated during virus replication
      and to determine the effects of N176 and N237 on nsp4 function and MHV
      replication, alanine substitutions of nsp4 N176, N237, or both were engineered
      into the MHV-A59 genome. The N176A, N237A, and N176A/N237A mutant viruses were
      viable, and N176 and N237 were glycosylated during infection of wild-type (wt)
      and mutant viruses. The nsp4 glycosylation mutants exhibited impaired virus
      growth and RNA synthesis, with the N237A and N176A/N237A mutant viruses
      demonstrating more profound defects in virus growth and RNA synthesis. Electron
      microscopic analysis of ultrastructure from infected cells demonstrated that the
      nsp4 mutants had aberrant morphology of virus-induced double-membrane vesicles
      (DMVs) compared to those infected with wt virus. The degree of altered DMV
      morphology directly correlated with the extent of impairment in viral RNA
      synthesis and virus growth of the nsp4 mutant viruses. The results indicate that
      nsp4 plays a critical role in the organization and stability of DMVs. The results
      also support the conclusion that the structure of DMVs is essential for efficient
      RNA synthesis and optimal replication of coronaviruses.

PMID- 19846527
TI  - Novel approach to the formulation of an Epstein-Barr virus antigen-based
      nasopharyngeal carcinoma vaccine.
AB  - Epstein-Barr virus (EBV) is associated with several malignant diseases including
      nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia.
      Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease
      is not uncommon. Therefore, there is a need for specific therapies that target
      the tumor through the recognition of EBV antigens. In NPC, latent membrane
      protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since
      they are typically expressed and T-cell determinants in each of these proteins
      have been defined. We have attempted to maximize the opportunity of incorporating
      every possible CD4 and CD8 determinant in a single formulation. We have achieved
      this by generating a scrambled protein incorporating random overlapping peptide
      sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication
      deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad
      SAVINE]). This report describes the construction of this Ad-SAVINE construct, its
      utility in generating LMP1 and LMP2 responses in healthy individuals as well as
      NPC patients, and its capacity to define new epitopes. This formulation could
      have a role in NPC immunotherapy for all ethnic groups since it has the potential
      to activate all possible CD4 and CD8 responses within EBNA1 and LMPs.

PMID- 19846528
TI  - Abrogation of the Brd4-positive transcription elongation factor B complex by
      papillomavirus E2 protein contributes to viral oncogene repression.
AB  - The cellular bromodomain protein Brd4 is a major interacting partner of the
      papillomavirus (PV) E2 protein. Interaction of E2 with Brd4 contributes to viral
      episome maintenance. The E2-Brd4 interaction also plays an important role in
      repressing viral oncogene expression from the integrated viral genome in human PV
      (HPV)-positive cancer cells. However, the underlying mechanism is not clearly
      understood. In host cells, Brd4 recruits positive transcription elongation factor
      b (P-TEFb) to stimulate RNA polymerase II phosphorylation during cellular and
      viral gene expression. P-TEFb associates with the C terminus of Brd4, which
      largely overlaps with the E2 binding site on Brd4. In this study, we demonstrate
      that E2 binding to Brd4 inhibits the interaction of endogenous Brd4 and P-TEFb. P
      TEFb is essential for viral oncogene E6/E7 transcription in both HeLa and CaSki
      cells that contain integrated HPV genomes. E2 binding to Brd4 abrogates the
      recruitment of P-TEFb to the integrated viral chromatin template, leading to
      inactivation of P-TEFb and repression of the viral oncogene E6/E7. Furthermore,
      dissociation of the Brd4-P-TEFb complex from the integrated viral chromatin
      template using a Brd4 bromodomain dominant-negative inhibitor also hampers HPV
      E6/E7 oncogene expression. Our data support that Brd4 recruitment of P-TEFb to
      the viral chromatin template is essential for viral oncogene expression.
      Abrogation of the interaction between P-TEFb and Brd4 thus provides a mechanism
      for E2-mediated repression of the viral oncogenes from the integrated viral
      genomes in cancer cells.

PMID- 19846529
TI  - Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads
      to induction of proinflammatory cytokines and SOCS1.
AB  - Ebola virus initially targets monocytes and macrophages, which can lead to the
      release of proinflammatory cytokines and chemokines. These inflammatory cytokines
      are thought to contribute to the development of circulatory shock seen in fatal
      Ebola virus infections. Here we report that host Toll-like receptor 4 (TLR4) is a
      sensor for Ebola virus glycoprotein (GP) on virus-like particles (VLPs) and that
      resultant TLR4 signaling pathways lead to the production of proinflammatory
      cytokines and suppressor of cytokine signaling 1 (SOCS1) in a human monocytic
      cell line and in HEK293-TLR4/MD2 cells stably expressing the TLR4/MD2 complex.
      Ebola virus GP was found to interact with TLR4 by immunoprecipitation/Western
      blot analyses, and Ebola virus GP on VLPs was able to stimulate expression of NF
      kappaB in a TLR4-dependent manner. Interestingly, we found that budding of Ebola
      virus VLPs was more pronounced in TLR4-stimulated cells than in unstimulated
      control cells. In sum, these findings identify the host innate immune protein
      TLR4 as a sensor for Ebola virus GP which may play an important role in the
      immunopathogenesis of Ebola virus infection.

PMID- 19846530
TI  - Andes virus recognition of human and Syrian hamster beta3 integrins is determined
      by an L33P substitution in the PSI domain.
AB  - Andes virus (ANDV) causes a fatal hantavirus pulmonary syndrome (HPS) in humans
      and Syrian hamsters. Human alpha(v)beta(3) integrins are receptors for several
      pathogenic hantaviruses, and the function of alpha(v)beta(3) integrins on
      endothelial cells suggests a role for alpha(v)beta(3) in hantavirus directed
      vascular permeability. We determined here that ANDV infection of human
      endothelial cells or Syrian hamster-derived BHK-21 cells was selectively
      inhibited by the high-affinity alpha(v)beta(3) integrin ligand vitronectin and by
      antibodies to alpha(v)beta(3) integrins. Further, antibodies to the beta(3)
      integrin PSI domain, as well as PSI domain polypeptides derived from human and
      Syrian hamster beta(3) subunits, but not murine or bovine beta(3), inhibited ANDV
      infection of both BHK-21 and human endothelial cells. These findings suggest that
      ANDV interacts with beta(3) subunits through PSI domain residues conserved in
      both Syrian hamster and human beta(3) integrins. Sequencing the Syrian hamster
      beta(3) integrin PSI domain revealed eight differences between Syrian hamster and
      human beta(3) integrins. Analysis of residues within the PSI domains of human,
      Syrian hamster, murine, and bovine beta(3) integrins identified unique proline
      substitutions at residues 32 and 33 of murine and bovine PSI domains that could
      determine ANDV recognition. Mutagenizing the human beta(3) PSI domain to contain
      the L33P substitution present in bovine beta(3) integrin abolished the ability of
      the PSI domain to inhibit ANDV infectivity. Conversely, mutagenizing either the
      bovine PSI domain, P33L, or the murine PSI domain, S32P, to the residue present
      human beta(3) permitted PSI mutants to inhibit ANDV infection. Similarly, CHO
      cells transfected with the full-length bovine beta(3) integrin containing the
      P33L mutation permitted infection by ANDV. These findings indicate that human and
      Syrian hamster alpha(v)beta(3) integrins are key receptors for ANDV and that
      specific residues within the beta(3) integrin PSI domain are required for ANDV
      infection. Since L33P is a naturally occurring human beta(3) polymorphism, these
      findings further suggest the importance of specific beta(3) integrin residues in
      hantavirus infection. These findings rationalize determining the role of beta(3)
      integrins in hantavirus pathogenesis in the Syrian hamster model.

PMID- 19846531
TI  - MKRN1 induces degradation of West Nile virus capsid protein by functioning as an
      E3 ligase.
AB  - West Nile virus capsid protein (WNVCp) displays pathogenic toxicity via the
      apoptotic pathway. However, a cellular mechanism protective against this toxic
      effect has not been observed so far. Here, we identified Makorin ring finger
      protein 1 (MKRN1) as a novel E3 ubiquitin ligase for WNVCp. The cytotoxic effects
      of WNVCp as well as its expression levels were inhibited in U2OS cells that
      stably expressed MKRN1. Immunoprecipitation analyses revealed an interaction
      between MKRN1 and WNVCp. Domain analysis indicated that the C terminus of MKRN1
      and the N terminus of WNVCp were required for the interaction. MKRN1 could induce
      WNVCp ubiquitination and degradation in a proteasome-dependent manner.
      Interestingly, the WNVCp mutant with amino acids 1 to 105 deleted WNVCp was
      degraded by MKRN1, whereas the mutant with amino acids 1 to 90 deleted was not.
      When three lysine sites at positions 101, 103, and 104 of WNVCp were replaced
      with alanine, MKRN1-mediated ubiquitination and degradation of the mutant were
      significantly inhibited, suggesting that these sites are required for the
      ubiquitination. Finally, U2OS cell lines stably expressing MKRN1 were resistant
      to cytotoxic effects of WNV. In contrast, cells depleted of MKRN1 were more
      susceptible to WNVCp cytotoxicity. Confirming this, overexpression of MKRN1
      significantly reduced, but depletion of MKRN1 increased, WNV proliferation in
      293T cells. Taken together, our results suggest that MKRN1 can protect cells from
      WNV by inducing WNVCp degradation.

PMID- 19846532
TI  - African swine fever virus polyprotein pp62 is essential for viral core
      development.
AB  - One of the most characteristic features of African swine fever virus gene
      expression is its use of two polyproteins, pp220 and pp62, to produce several
      structural proteins that account for approximately 32% of the total protein
      virion mass. Equimolecular amounts of these proteins are the major components of
      the core shell, a thick protein layer that lies beneath the inner envelope,
      surrounding the viral nucleoid. Polyprotein pp220, which is located immediately
      underneath the internal envelope, is essential for the encapsidation of the core
      of the viral particle. In its absence, the infection produces essentially
      coreless particles. In this study we analyzed, by means of an IPTG (isopropyl
      beta-d-thiogalactopyranoside)-inducible virus, the role of polyprotein pp62 in
      virus assembly. Polyprotein pp62 is indispensable for viral replication. The
      repression of polyprotein pp62 expression does not alter late gene expression or
      the proteolytic processing of the polyprotein pp220. However, it has a profound
      impact on the subcellular localization of polyprotein pp220. Electron microscopy
      studies revealed that polyprotein pp62 is necessary for the correct assembly and
      maturation of the core of the viral particle. Its repression leads to the
      appearance of a significant fraction of empty particles, to an increase in the
      number of immature-like particles, and to the accumulation of defective
      particles. Immunoelectron microscopy analysis showed a clear correlation between
      the amount of polyprotein pp62, the quantity of polyprotein pp220, and the state
      of development of the core, suggesting that the complete absence of polyprotein
      pp62 during morphogenesis would produce a homogenous population of empty
      particles.

PMID- 19846533
TI  - A forward genetic strategy reveals destabilizing mutations in the Ebolavirus
      glycoprotein that alter its protease dependence during cell entry.
AB  - Ebolavirus (EBOV) entry into cells requires proteolytic disassembly of the viral
      glycoprotein, GP. This proteolytic processing, unusually extensive for an
      enveloped virus entry protein, is mediated by cysteine cathepsins, a family of
      endosomal/lysosomal proteases. Previous work has shown that cleavage of GP by
      cathepsin B (CatB) is specifically required to generate a critical entry
      intermediate. The functions of this intermediate are not well understood. We used
      a forward genetic strategy to investigate this CatB-dependent step. Specifically,
      we generated a replication-competent recombinant vesicular stomatitis virus
      bearing EBOV GP as its sole entry glycoprotein and used it to select viral
      mutants resistant to a CatB inhibitor. We obtained mutations at six amino acid
      positions in GP that independently confer complete resistance. All of the
      mutations reside at or near the GP1-GP2 intersubunit interface in the membrane
      proximal base of the prefusion GP trimer. This region forms a part of the "clamp"
      that holds the fusion subunit GP2 in its metastable prefusion conformation.
      Biochemical studies suggest that most of the mutations confer CatB independence
      not by altering specific cleavage sites in GP but rather by inducing
      conformational rearrangements in the prefusion GP trimer that dramatically
      enhance its susceptibility to proteolysis. The remaining mutants did not show the
      preceding behavior, indicating the existence of multiple mechanisms for acquiring
      CatB independence during entry. Altogether, our findings suggest that CatB
      cleavage is required to facilitate the triggering of viral membrane fusion by
      destabilizing the prefusion conformation of EBOV GP.

PMID- 19846534
TI  - MDA5 and MAVS mediate type I interferon responses to coxsackie B virus.
AB  - Coxsackie B viruses (CVB) are enteroviruses that have been associated with a
      variety of human diseases, including myocarditis. In the present study, we found
      that MDA5 and its adaptor molecule MAVS are critical for type I interferon
      responses to CVB, since the absence of either MAVS or MDA5 leads to deficient
      type I interferon production and early mortality in mice infected with CVB.
      Pancreatic and hepatic necrosis were observed on histopathological examination of
      MAVS and MDA5 knockout mice infected with CVB. Inflammatory cytokine production
      in response to systemic CVB infection was independent of MAVS. Surprisingly,
      virus titers were not elevated in MAVS-deficient mice, despite significant
      reductions in type I interferon levels. These data highlight the importance of
      type I interferon in host defense and provide insight on the mechanisms of innate
      immune responses following coxsackievirus infection.

PMID- 19846535
TI  - Effect of killer immunoglobulin-like receptors in the response to combined
      treatment in patients with chronic hepatitis C virus infection.
AB  - Killer immunoglobulin-like receptors (KIRs) are related to the activation and
      inhibition of NK cells and may play an important role in the innate response
      against infection with viruses such as hepatitis C virus (HCV). We examined
      whether the different combinations of KIRs with their HLA class I ligands
      influenced the response to combined treatment (pegylated alpha interferon and
      ribavirin) of patients infected by HCV. A total of 186 consecutive patients
      diagnosed with chronic HCV infection were analyzed. Seventy-seven patients
      exhibited HCV RNA levels at 6 months posttreatment and were called nonresponders
      (NR), while 109 cleared viral RNA and were named sustained viral responders
      (SVR). Patients were typed for HLA-B, HLA-Cw, KIR genes, and HCV genotype. In our
      study, the frequency of the KIR2DL2 allele was significantly increased in NR (P <
      0.001; odds ratio [OR] = 1.95), as was the frequency of the KIR2DL2/KIR2DL2
      genotype (P < 0.005; OR = 2.52). In contrast, the frequencies of the KIR2DL3
      genotype (P < 0.001) and KIR2DL3/KIR2DL3 genotype (P < 0.05; OR = 0.54) were
      significantly increased in the SVR. Different combinations of KIR2DL2 and KIR2DL3
      alleles with their ligands were analyzed. The frequency of the KIR2DL2/KIR2DL2
      HLA-C1C2 genotype was significantly increased in the NR (P < 0.01; OR = 3.15).
      Additionally, we found a higher frequency of the KIR2DL3/KIR2DL3-HLA-C1C1
      genotype in the SVR group (P < 0.05; OR = 0.33). These results were not affected
      by the HCV genotype. In conclusion, patients who carried the KIR2DL2/KIR2DL2-HLA
      C1C2 genotype were less prone to respond to treatment. However, the
      KIR2DL3/KIR2DL3-HLA-C1C1 genotype clearly correlated with a satisfactory response
      to treatment, defined by the clearance of HCV RNA.

PMID- 19846536
TI  - Upstream stimulatory factor 2, a novel FoxA1-interacting protein, is involved in
      prostate-specific gene expression.
AB  - The forkhead protein A1 (FoxA1) is critical for the androgenic regulation of
      prostate-specific promoters. Prostate tissue rescued from FoxA1 knockout mice
      exhibits abnormal prostate development, typified by the absence of expression of
      differentiation markers and inability to engage in secretion. Chromatin
      immunoprecipitation and coimmunoprecipitation studies revealed that FoxA1 is one
      of the earliest transcription factors that binds to prostate-specific promoters,
      and that a direct protein-protein interaction occurs between FoxA1 and androgen
      receptor. Interestingly, evidence of the interaction of FoxA1 with other
      transcription factors is lacking. The upstream stimulatory factor 2 (USF2), an E
      box-binding transcription factor of the basic-helix-loop-helix-leucine-zipper
      family, binds to a consensus DNA sequence similar to FoxA1. Our in vitro and in
      vivo studies demonstrate the binding of USF2 to prostate-specific gene promoters
      including the probasin promoter, spermine-binding protein promoter, and prostate
      specific antigen core enhancer. Furthermore, we show a direct physical
      interaction between FoxA1 and USF2 through the use of immunoprecipitation and
      glutathione-S-transferase pull-down assays. This interaction is mediated via the
      forkhead DNA-binding domain of FoxA1 and the DNA-binding domain of USF2. In
      summary, these data indicate that USF2 is one of the components of the
      FoxA1/androgen receptor transcriptional protein complex that contributes to the
      expression of androgen-regulated and prostate-specific genes.

PMID- 19846537
TI  - Regulation of GPR54 signaling by GRK2 and {beta}-arrestin.
AB  - Kisspeptin and its receptor, GPR54, are major regulators of the hypothalamic
      pituitary-gonadal axis as well as regulators of human placentation and tumor
      metastases. GPR54 is a G(q/11)-coupled G protein-coupled receptor (GPCR), and
      activation by kisspeptin stimulates phosphatidy linositol 4, 5-biphosphate
      hydrolysis, Ca(2+) mobilization, arachidonic acid release, and ERK1/2 MAPK
      phosphorylation. Physiological evidence suggests that GPR54 undergoes agonist
      dependent desensitization, but underlying molecular mechanisms are unknown.
      Furthermore, very little has been reported on the early events that regulate
      GPR54 signaling. The lack of information in these important areas led to this
      study. Here we report for the first time on the role of GPCR serine/threonine
      kinase (GRK)2 and beta-arrestin in regulating GPR54 signaling in human embryonic
      kidney (HEK) 293 cells, a model cell system for studying the molecular regulation
      of GPCRs, and genetically modified MDA MB-231 cells, an invasive breast cancer
      cell line expressing about 75% less beta-arrestin-2 than the control cell line.
      Our study reveals that in HEK 293 cells, GPR54 is expressed both at the plasma
      membrane and intracellularly and also that plasma membrane expression is
      regulated by cytoplasmic tail sequences. We also demonstrate that GPR54 exhibits
      constitutive activity, internalization, and association with GRK2 and beta-
      arrestins-1 and 2 through sequences in the second intracellular loop and
      cytoplasmic tail of the receptor. We also show that GRK2 stimulates the
      desensitization of GPR54 in HEK 293 cells and that beta-arrestin-2 mediates GPR54
      activation of ERK1/2 in MDA-MB-231 cells. The significance of these findings in
      developing molecular-based therapies for treating certain endocrine-related
      disorders is discussed.

PMID- 19846538
TI  - Genomic priming of the antisecretory response to estrogen in rat distal colon
      throughout the estrous cycle.
AB  - The secretion of Cl(-) across distal colonic crypt cells provides the driving
      force for the movement of fluid into the luminal space. 17beta-Estradiol (E2)
      produces a rapid and sustained reduction in secretion in females, which is
      dependent on the novel protein kinase C delta (PKC delta) isozyme and PKA isoform
      I targeting of KCNQ1 channels. This sexual dimorphism in the E2 response is
      associated with a higher expression level of PKC delta in female compared with
      the male tissue. The present study revealed the antisecretory response is
      regulated throughout the female reproductive (estrous) cycle and is primed by
      genomic regulation of the kinases. E2 (1-10 nm) decreased cAMP-dependent
      secretion in colonic epithelia during the estrus, metestrus, and diestrus stages.
      A weak inhibition of secretion was demonstrated in the proestrus stage. The
      expression levels of PKC delta and PKA fluctuated throughout the estrous cycle
      and correlated with the potency of the antisecretory effect of E2. The expression
      of PKC delta and PKA were up-regulated by estrogen at a transcriptional level via
      a PKC delta-MAPK-cAMP response element-binding protein-regulated pathway
      indicating a genomic priming of the antisecretory response. PK Cdelta was
      activated by the membrane-impermeant E2-BSA, and this response was inhibited by
      the estrogen receptor antagonist ICI 182,780. The 66-kDa estrogen receptor-alpha
      isoform was present at the plasma membrane of female colonic crypt cells with a
      lower abundance found in male colonic crypts. The study demonstrates estrogen
      regulation of intestinal secretion both at a rapid and transcriptional level,
      demonstrating an interdependent relationship between both nongenomic and genomic
      hormone responses.

PMID- 19846539
TI  - Minireview: the SRC family of coactivators: an entree to understanding a subset
      of polygenic diseases?
AB  - In this perspective, we present the idea that SRC family coactivators are likely
      agents in human polygenic disease states based upon a number of interlocking
      aspects of their biology. We argue that their role as key integrators of
      environmental signals and their ability to regulate the expression of myriad
      downstream genes makes them likely candidates for strong positive evolutionary
      selection pressures. Based on the fact that they work as part of multiprotein
      coactivator complexes, we predict that individual coactivator alleles exist as
      weakly penetrant disease alleles, each contributing only a fraction of
      transcriptional activity to the whole coactivator complex. In this way,
      individual coactivator alleles are free to evolve in the absence of strong
      negative selection. Emerging genomic and proteomic approaches promise to advance
      the characterization of coactivator proteins and their physiological functions,
      allowing us to have a greater appreciation of their roles as master regulators at
      the nexus between genetics, reproduction, metabolism, cancer, other human
      diseases, and our environment.

PMID- 19846540
TI  - Osmotic stress regulates mineralocorticoid receptor expression in a novel
      aldosterone-sensitive cortical collecting duct cell line.
AB  - Aldosterone effects are mediated by the mineralocorticoid receptor (MR), a
      transcription factor highly expressed in the distal nephron. Given that MR
      expression level constitutes a key element controlling hormone responsiveness,
      there is much interest in elucidating the molecular mechanisms governing MR
      expression. To investigate whether hyper- or hypotonicity could affect MR
      abundance, we established by targeted oncogenesis a novel immortalized cortical
      collecting duct (CCD) cell line and examined the impact of osmotic stress on MR
      expression. KC3AC1 cells form domes, exhibit a high transepithelial resistance,
      express 11beta-hydroxysteroid dehydrogenase 2 and functional endogenous MR, which
      mediates aldosterone-stimulated Na(+) reabsorption through the epithelial sodium
      channel activation. MR expression is tightly regulated by osmotic stress.
      Hypertonic conditions induce expression of tonicity-responsive enhancer binding
      protein, an osmoregulatory transcription factor capable of binding tonicity
      responsive enhancer response elements located in MR regulatory sequences.
      Surprisingly, hypertonicity leads to a severe reduction in MR transcript and
      protein levels. This is accompanied by a concomitant tonicity-induced expression
      of Tis11b, a mRNA-destabilizing protein that, by binding to the AU-rich sequences
      of the 3'-untranslated region of MR mRNA, may favor hypertonicity-dependent
      degradation of labile MR transcripts. In sharp contrast, hypotonicity causes a
      strong increase in MR transcript and protein levels. Collectively, we demonstrate
      for the first time that optimal adaptation of CCD cells to changes in
      extracellular fluid composition is accompanied by drastic modification in MR
      abundance via transcriptional and posttranscriptional mechanisms. Osmotic stress
      regulated MR expression may represent an important molecular determinant for cell
      specific MR action, most notably in renal failure, hypertension, or
      mineralocorticoid resistance.

PMID- 19846541
TI  - Petunia hybrida CAROTENOID CLEAVAGE DIOXYGENASE7 is involved in the production of
      negative and positive branching signals in petunia.
AB  - One of the key factors that defines plant form is the regulation of when and
      where branches develop. The diversity of form observed in nature results, in
      part, from variation in the regulation of branching between species. Two
      CAROTENOID CLEAVAGE DIOXYGENASE (CCD) genes, CCD7 and CCD8, are required for the
      production of a branch-suppressing plant hormone. Here, we report that the
      decreased apical dominance3 (dad3) mutant of petunia (Petunia hybrida) results
      from the mutation of the PhCCD7 gene and has a less severe branching phenotype
      than mutation of PhCCD8 (dad1). An analysis of the expression of this gene in
      wild-type, mutant, and grafted petunia suggests that in petunia, CCD7 and CCD8
      are coordinately regulated. In contrast to observations in Arabidopsis
      (Arabidopsis thaliana), ccd7ccd8 double mutants in petunia show an additive
      phenotype. An analysis using dad3 or dad1 mutant scions grafted to wild-type
      rootstocks showed that when these plants produce adventitious mutant roots,
      branching is increased above that seen in plants where the mutant roots are
      removed. The results presented here indicate that mutation of either CCD7 or CCD8
      in petunia results in both the loss of an inhibitor of branching and an increase
      in a promoter of branching.

PMID- 19846542
TI  - Arabidopsis FAB1/PIKfyve proteins are essential for development of viable pollen.
AB  - Phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)] is a phospholipid that
      has a role in controlling membrane trafficking events in yeast and animal cells.
      The function of this lipid in plants is unknown, although its synthesis has been
      shown to be up-regulated upon osmotic stress in plant cells. PtdIns(3,5)P(2) is
      synthesized by the PIKfyve/Fab1 family of proteins, with two orthologs, FAB1A and
      FAB1B, being present in Arabidopsis (Arabidopsis thaliana). In this study, we
      attempt to address the role of this lipid by analyzing the phenotypes of plants
      mutated in FAB1A and FAB1B. It was not possible to generate plants homozygous for
      mutations in both genes, although single mutants were isolated. Both homozygous
      single mutant plant lines exhibited a leaf curl phenotype that was more marked in
      FAB1B mutants. Genetic transmission analysis revealed that failure to generate
      double mutant lines was entirely due to inviability of pollen carrying mutant
      alleles of both FAB1A and FAB1B. This pollen displayed severe defects in vacuolar
      reorganization following the first mitotic division of development. The presence
      of abnormally large vacuoles in pollen at the tricellular stage resulted in the
      collapse of the majority of grains carrying both mutant alleles. This
      demonstrates a crucial role for PtdIns(3,5)P(2) in modulating the dynamics of
      vacuolar rearrangement essential for successful pollen development. Taken
      together, our results are consistent with PtdIns(3,5)P(2) production being
      central to cellular responses to changes in osmotic conditions.

PMID- 19846543
TI  - Nutrient content not a primary issue in choosing to buy organic foods.

PMID- 19846544
TI  - Effect of a dietary intervention and n-3 fatty acid supplementation on measures
      of serum lipid and insulin sensitivity in persons with HIV.
AB  - BACKGROUND: Elevated serum triglyceride and low HDL-cholesterol concentrations
      have been reported in persons with HIV. OBJECTIVE: The effect of a dietary
      intervention plus n-3 (omega-3) fatty acid supplementation on serum triglycerides
      and markers of insulin sensitivity was investigated. DESIGN: Fifty-four persons
      with HIV and elevated serum triglycerides (>150 mg/dL) and/or abnormal
      Quantitative Insulin Sensitivity Check Index values (<0.35 but >0.30) were
      recruited for a dietary intervention in which total fat, type of fat, fiber, and
      glycemic load were controlled along with supplementation with n-3 fatty acids to
      achieve an intake of 6 g/d. The subjects were randomly assigned to an
      intervention or control group, and serum lipids, markers of insulin sensitivity,
      and serum phospholipid fatty acids were measured in both groups at baseline, 3
      wk, and 13 wk. RESULTS: Triglycerides in the intervention group decreased from a
      median of 180 mg/dL (interquartile range: 141, 396) to 114 mg/dL (interquartile
      range: 84, 169) from baseline to 3 wk, whereas they remained stable in the
      control group (P = 0.003). Serum phospholipid fatty acids indicated a decrease in
      de novo lipogenesis and a decrease in arachidonic acid (% nmol; P <or= 0.001) in
      the intervention group. At 3 wk, the insulin area under the curve decreased but
      not significantly. CONCLUSIONS: Diet and n-3 fatty acid supplementation
      dramatically reduced serum triglycerides, decreased arachidonic acid in the
      phospholipids fraction, and appeared to decrease the de novo lipogenesis
      associated with the metabolic syndrome in the intervention group.

PMID- 19846545
TI  - Effect of high-normal compared with low-normal arterial pH on protein balances in
      automated peritoneal dialysis patients.
AB  - BACKGROUND: Although the protein catabolic effects of metabolic acidosis are well
      established, it is unclear whether the entire reference range of arterial pH
      (7.37-7.44) is equivalent for protein balance. OBJECTIVE: We undertook this study
      to test the hypothesis that in patients undergoing automated peritoneal dialysis,
      an arterial pH of 7.43-7.45, as compared with a pH of 7.36-7.38, is associated
      with more-positive nitrogen balances. DESIGN: Eight stable subjects (5 men) aged
      43.1 +/- 15.3 y completed a randomized, crossover nitrogen balance study for
      >or=42 d. Arterial pH was varied by changing the daily doses of sodium
      citrate/citric acid and ammonium chloride. RESULTS: The subjects attained mean
      (+/-SD) arterial pH values of 7.37 +/- 0.01 and 7.44 +/- 0.02 during the low
      normal and high-normal pH phases, respectively. The higher arterial pH was
      associated with higher net nitrogen balances (3.22 +/- 1.37 compared with 2.29 +/
      2.18 g/d; P = 0.06), lower serum urea nitrogen (54.1 +/- 13.7 compared with 64.4
      +/- 20.2 mg/dL; P = 0.01), higher fasting leucine flux (P = 0.02), and increased
      fasting total-body protein synthesis (P = 0.01) and degradation (P = 0.02). In 7
      of 8 study subjects, nitrogen balances were more positive at the higher arterial
      pH (P = 0.004). There were no significant changes in anthropometric measurements,
      other biochemical measurements, and the mRNA content of selected proteins in
      skeletal muscle. CONCLUSION: This study suggests that in most stable automated
      peritoneal dialysis patients, a mean arterial pH of 7.44, as compared with 7.37,
      is associated with more-positive nitrogen balances. This trial was registered at
      clinical trials.gov as NCT00586131.

PMID- 19846546
TI  - Short-term sleep loss decreases physical activity under free-living conditions
      but does not increase food intake under time-deprived laboratory conditions in
      healthy men.
AB  - BACKGROUND: Short sleep duration is correlated with an increased risk of
      developing obesity and cardiovascular disease, but the mechanisms behind this
      relation are largely unknown. OBJECTIVE: We aimed to test the hypothesis that
      acute sleep loss decreases physical activity while increasing food intake,
      thereby shifting 2 crucial behavioral components of energy homeostasis toward
      weight gain. DESIGN: In 15 healthy, normal-weight men, spontaneous physical
      activity was registered by accelerometry during the entire experiment, and food
      intake as well as relevant hormones were assessed during a 15-h daytime period
      after 2 nights of regular sleep (bed time: 2245-0700) and after 2 nights of
      restricted sleep (bed time: 0245-0700). Experiments were performed in a crossover
      design. RESULTS: Sleep restriction significantly decreased physical activity
      during the daytime spent under free-living conditions after the first night of
      sleep manipulation (P = 0.008). Also, intensities of physical activity were
      shifted toward lower levels, with less time spent with intense activities (P =
      0.046). Total energy intake, feelings of hunger, and appetite as well as ghrelin
      and leptin concentrations during day 2 remained unaffected by acute sleep
      restriction. CONCLUSIONS: In contrast to our expectation, short-term sleep loss
      neither increased food intake nor affected concentrations of the hunger
      regulating hormones leptin and ghrelin. However, the observed decrease in daytime
      physical activity may point to another potentially important behavioral mechanism
      for the health-impairing influence of sleep loss.

PMID- 19846547
TI  - Methodologic flaws in selecting studies and comparing nutrient concentrations led
      Dangour et al to miss the emerging forest amid the trees.

PMID- 19846548
TI  - CLOCK genetic variation and metabolic syndrome risk: modulation by
      monounsaturated fatty acids.
AB  - BACKGROUND: Disruption of the circadian system may be causal for manifestations
      of the metabolic syndrome (MetS). OBJECTIVE: The objective was to study the
      associations of 5 CLOCK polymorphisms with MetS features by analyzing fatty acid
      (FA) composition from dietary and red blood cell (RBC) membrane sources. DESIGN:
      Participants (n = 1100) in the Genetics of Lipid Lowering Drugs and Diet Network
      (GOLDN) study were included. Dietary intake was estimated with a validated
      questionnaire. Anthropometric and biochemical measurements and genotypes were
      determined. Postprandial lipids and the FA composition of RBC membranes were
      analyzed. RESULTS: CLOCK single nucleotide polymorphisms were significantly
      associated with obesity and individual components of MetS. For single nucleotide
      polymorphism rs4580704, minor allele carriers had a 46% lower risk of
      hypertension than did noncarriers. The monounsaturated fatty acid (MUFA) content
      of RBC membranes, particularly oleic acid, changed according to CLOCK genetic
      variants (P < 0.05). We identified significant gene-diet interactions associated
      with MetS at the CLOCK locus. By dichotomizing MUFA intake, we found different
      effects across rs4580704 genotypes for glucose (P = 0.020) and insulin resistance
      (P = 0.026). The protective effect of the minor allele on insulin sensitivity was
      only present when MUFA intake was >13.2% of energy. We also found different
      effects across CLOCK 3111T-->C genotypes for saturated fatty acid intake (% of
      energy) (P = 0.017). The deleterious effect of gene variants on waist
      circumference was only found with high saturated fatty acid intakes (>11.8%).
      CONCLUSIONS: CLOCK polymorphisms interact with FAs to modulate MetS traits. The
      dietary source and membrane content of MUFAs are implicated in the relations
      between alterations in the circadian system and MetS.

PMID- 19846549
TI  - Identification of anabolic selective androgen receptor modulators with reduced
      activities in reproductive tissues and sebaceous glands.
AB  - Androgen replacement therapy is a promising strategy for the treatment of
      frailty; however, androgens pose risks for unwanted effects including
      virilization and hypertrophy of reproductive organs. Selective Androgen Receptor
      Modulators (SARMs) retain the anabolic properties of androgens in bone and muscle
      while having reduced effects in other tissues. We describe two structurally
      similar 4-aza-steroidal androgen receptor (AR) ligands, Cl-4AS-1, a full agonist,
      and TFM-4AS-1, which is a SARM. TFM-4AS-1 is a potent AR ligand (IC(50), 38 nm)
      that partially activates an AR-dependent MMTV promoter (55% of maximal response)
      while antagonizing the N-terminal/C-terminal interaction within AR that is
      required for full receptor activation. Microarray analyses of MDA-MB-453 cells
      show that whereas Cl-4AS-1 behaves like 5alpha-dihydrotestosterone (DHT), TFM-4AS
      1 acts as a gene-selective agonist, inducing some genes as effectively as DHT and
      others to a lesser extent or not at all. This gene-selective agonism manifests as
      tissue-selectivity: in ovariectomized rats, Cl-4AS-1 mimics DHT while TFM-4AS-1
      promotes the accrual of bone and muscle mass while having reduced effects on
      reproductive organs and sebaceous glands. Moreover, TFM-4AS-1 does not promote
      prostate growth and antagonizes DHT in seminal vesicles. To confirm that the
      biochemical properties of TFM-4AS-1 confer tissue selectivity, we identified a
      structurally unrelated compound, FTBU-1, with partial agonist activity coupled
      with antagonism of the N-terminal/C-terminal interaction and found that it also
      behaves as a SARM. TFM-4AS-1 and FTBU-1 represent two new classes of SARMs and
      will allow for comparative studies aimed at understanding the biophysical and
      physiological basis of tissue-selective effects of nuclear receptor ligands.

PMID- 19846550
TI  - Characterization of the key step for light-driven hydrogen evolution in green
      algae.
AB  - Under anaerobic conditions, several species of green algae perform a light
      dependent hydrogen production catalyzed by a special group of [FeFe] hydrogenases
      termed HydA. Although highly interesting for biotechnological applications, the
      direct connection between photosynthetic electron transport and hydrogenase
      activity is still a matter of speculation. By establishing an in vitro
      reconstitution system, we demonstrate that the photosynthetic ferredoxin (PetF)
      is essential for efficient electron transfer between photosystem I and HydA1. To
      investigate the electrostatic interaction process and electron transfer between
      PetF and HydA1, we performed site-directed mutagenesis. Kinetic analyses with
      several site-directed mutagenesis variants of HydA1 and PetF enabled us to
      localize the respective contact sites. These experiments in combination with in
      silico docking analyses indicate that electrostatic interactions between the
      conserved HydA1 residue Lys(396) and the C terminus of PetF as well as between
      the PetF residue Glu(122) and the N-terminal amino group of HydA1 play a major
      role in complex formation and electron transfer. Mapping of relevant HydA1 and
      PetF residues constitutes an important basis for manipulating the physiological
      photosynthetic electron flow in favor of light-driven H(2) production.

PMID- 19846551
TI  - Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation
      of c27 steroids.
AB  - Cyp125 (Rv3545c), a cytochrome P450, is encoded as part of the cholesterol
      degradation gene cluster conserved among members of the Mycobacterium
      tuberculosis complex. This enzyme has been implicated in mycobacterial
      pathogenesis, and a homologue initiates cholesterol catabolism in the soil
      actinomycete Rhodococcus jostii RHA1. In Mycobacterium bovis BCG, cyp125 was up
      regulated 7.1-fold with growth on cholesterol. A cyp125 deletion mutant of BCG
      did not grow on cholesterol and accumulated 4-cholesten-3-one when incubated in
      the presence of cholesterol. Wild-type BCG grew on this metabolite. By contrast,
      a parallel cyp125 deletion mutation of M. tuberculosis H37Rv did not affect
      growth on cholesterol. Purified Cyp125 from M. tuberculosis, heterologously
      produced in R. jostii RHA1, bound cholesterol and 4-cholesten-3-one with apparent
      dissociation constants of 0.20 +/- 0.02 microM and 0.27 +/- 0.05 microm,
      respectively. When reconstituted with KshB, the cognate reductase of the
      ketosteroid 9alpha-hydroxylase, Cyp125 catalyzed the hydroxylation of these
      steroids. MS and NMR analyses revealed that hydroxylation occurred at carbon 26
      of the steroid side chain, allowing unambiguous classification of Cyp125 as a
      steroid C26-hydroxylase. This study establishes the catalytic function of Cyp125
      and, in identifying an important difference in the catabolic potential of M.
      bovis and M. tuberculosis, suggests that Cyp125 may have an additional function
      in pathogenesis.

PMID- 19846552
TI  - The Structure of Mycobacterium tuberculosis CYP125: molecular basis for
      cholesterol binding in a P450 needed for host infection.
AB  - We report characterization and the crystal structure of the Mycobacterium
      tuberculosis cytochrome P450 CYP125, a P450 implicated in metabolism of host
      cholesterol and essential for establishing infection in mice. CYP125 is purified
      in a high spin form and undergoes both type I and II spectral shifts with various
      azole drugs. The 1.4-A structure of ligand-free CYP125 reveals a "letterbox"
      active site cavity of dimensions appropriate for entry of a polycyclic sterol. A
      mixture of hexa-coordinate and penta-coordinate states could be discerned, with
      water binding as the 6th heme-ligand linked to conformation of the I-helix
      Val(267) residue. Structures in complex with androstenedione and the
      antitubercular drug econazole reveal that binding of hydrophobic ligands occurs
      within the active site cavity. Due to the funnel shape of the active site near
      the heme, neither approaches the heme iron. A model of the cholesterol CYP125
      complex shows that the alkyl side chain extends toward the heme iron, predicting
      hydroxylation of cholesterol C27. The alkyl chain is in close contact to
      Val(267), suggesting a substrate binding-induced low- to high-spin transition
      coupled to reorientation of the latter residue. Reconstitution of CYP125 activity
      with a redox partner system revealed exclusively cholesterol 27-hydroxylation,
      consistent with structure and modeling. This activity may enable catabolism of
      host cholesterol or generation of immunomodulatory compounds that enable
      persistence in the host. This study reveals structural and catalytic properties
      of a potential M. tuberculosis drug target enzyme, and the likely mode by which
      the host-derived substrate is bound and hydroxylated.

PMID- 19846553
TI  - Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and
      survival of both osteoblasts and osteoclasts.
AB  - The anti-apoptotic molecule Bcl-2 inhibits apoptosis by preventing cytochrome c
      release from mitochondria. Although several studies have indicated the importance
      of Bcl-2 in maintaining skeletal integrity, the detailed cellular and molecular
      mechanisms remain elusive. Bcl-2(-/-) mice are growth-retarded and exhibit
      increased bone volume of the primary spongiosa, mainly due to the decreased
      number and dysfunction of osteoclasts. Osteoblast function is also impaired in
      Bcl-2(-/-) mice. Ex vivo studies on osteoblasts and osteoclasts showed that Bcl-2
      promoted the differentiation, activation, and survival of both cell types.
      Because Bcl-2(-/-) mice die before 6 weeks of age due to renal failure and cannot
      be compared with adult wild type mice, we generated Bcl-2(-/-)Bim(+/-) mice, in
      which a single Bim allele was inactivated, and compared them with their Bcl-2(+/
      )Bim(+/-) littermates. Loss of a single Bim allele restored normal osteoclast
      function in Bcl-2(-/-) mice but did not restore the impaired function of
      osteoblasts, and the mice exhibited osteopenia. These data demonstrate that Bcl-2
      promotes the differentiation, activity, and survival of both osteoblasts and
      osteoclasts. The balance between Bcl-2 and Bim regulates osteoclast apoptosis and
      function, whereas other pro-apoptotic members are important for osteoblasts.

PMID- 19846554
TI  - Non-proteolytic regulation of p53-mediated transcription through destabilization
      of the activator.promoter complex by the proteasomal ATPases.
AB  - It has been shown previously that sub-complexes of the 26 S proteasome can
      regulate gene expression via non-proteolytic mechanisms. One such mechanism is
      the disruption of activator.promoter complexes in an ATP-dependent fashion, which
      was discovered in the context of the yeast Gal4 system. This activity strongly
      inhibits Gal4-driven gene expression unless the activator is mono-ubiquitylated,
      which protects it from the ATPases. To address whether this paradigm is also
      applicable to medically important mammalian transcriptional activators we report
      here a study of the interaction of the proteasomal ATPases with p53. It is shown
      that p53 binds directly to the ATPases via its C-terminal tetramerization and
      regulatory domain and that p53.promoter complexes are indeed vulnerable to ATPase
      dependent disruption by the ATPase complex in vitro. Knockdown of one of the
      ATPases, Rpt6, in living cells results in increased occupancy of the p21(waf1)
      promoter by p53 and increased expression of the gene, consistent with the idea
      that the proteasomal ATPases negatively regulate p53 function in a non
      proteolytic fashion.

PMID- 19846555
TI  - Versatile loops in mycocypins inhibit three protease families.
AB  - Mycocypins, clitocypins and macrocypins, are cysteine protease inhibitors
      isolated from the mushrooms Clitocybe nebularis and Macrolepiota procera. Lack of
      sequence homology to other families of protease inhibitors suggested that
      mycocypins inhibit their target cysteine protease by a unique mechanism and that
      a novel fold may be found. The crystal structures of the complex of clitocypin
      with the papain-like cysteine protease cathepsin V and of macrocypin and
      clitocypin alone have revealed yet another motif of binding to papain like
      cysteine proteases, which in a yet unrevealed way occludes the catalytic residue.
      The binding is associated with a peptide-bond flip of glycine that occurs before
      or concurrently with the inhibitor docking. Mycocypins possess a beta-trefoil
      fold, the hallmark of Kunitz-type inhibitors. It is a tree-like structure with
      two loops in the root region, a stem comprising a six-stranded beta-barrel, and
      two layers of loops (6 + 3) in the crown region. The two loops that bind to
      cysteine cathepsins belong to the lower layer of the crown loops, whereas a
      single loop from the crown region can inhibit trypsin or asparaginyl
      endopeptidase, as demonstrated by site-directed mutagenesis. These loops present
      a versatile surface with the potential to bind to additional classes of
      proteases. When appropriately engineered, they could provide the basis for
      possible exploitation in crop protection.

PMID- 19846557
TI  - Regulation of homotypic cell-cell adhesion by branched N-glycosylation of N
      cadherin extracellular EC2 and EC3 domains.
AB  - The effects of altering N-cadherin N-glycosylation on several cadherin-mediated
      cellular behaviors were investigated using small interfering RNA and site
      directed mutagenesis. In HT1080 fibrosarcoma cells, small interfering RNA
      directed knockdown of N-acetylglucosaminyltransferase V (GnT-V), a
      glycosyltransferase up-regulated by oncogene signaling, caused decreased
      expression of N-linked beta(1,6)-branched glycans expressed on N-cadherin,
      resulting in enhanced N-cadherin-mediated cell-cell adhesion, but had no effect
      on N-cadherin expression on the cell surface. This effect on adhesion was
      accompanied by decreased cell migration and invasion, opposite of the effects
      observed when GnT-V was overexpressed in these cells (Guo, H. B., Lee, I., Kamar,
      M., and Pierce, M. (2003) J. Biol. Chem. 278, 52412-52424). A detailed study
      using site-directed mutagenesis demonstrated that three of the eight putative N
      glycosylation sites in the N-cadherin sequence showed N-glycan expression.
      Moreover, all three of these sites, located in the extracellular domains EC2 and
      EC3, were shown by leucoagglutinating phytohemagglutinin binding to express at
      least some beta(1,6)-branched glycans, products of GnT-V activity. Deletion of
      these sites had no effect on cadherin levels on the cell surface but led to
      increased stabilization of cell-cell contacts, cell-cell adhesion- mediated
      intracellular signaling, and reduced cell migration. We show for the first time
      that these deletions had little effect on formation of the N-cadherin-catenin
      complex but instead resulted in increased N-cadherin cis-dimerization. Branched N
      glycan expression at three sites in the EC2 and -3 domains regulates N-cadherin
      mediated cell-cell contact formation, outside-in signaling, and cell migration
      and is probably a significant contributor to the increase in the
      migratory/invasive phenotype of cancer cells that results when GnT-V activity is
      up-regulated by oncogene signaling.

PMID- 19846556
TI  - Multiple binding modes between HNF4alpha and the LXXLL motifs of PGC-1alpha lead
      to full activation.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) is a novel nuclear receptor that
      participates in a hierarchical network of transcription factors regulating the
      development and physiology of such vital organs as the liver, pancreas, and
      kidney. Among the various transcriptional coregulators with which HNF4alpha
      interacts, peroxisome proliferation-activated receptor gamma (PPARgamma)
      coactivator 1alpha (PGC-1alpha) represents a novel coactivator whose activation
      is unusually robust and whose binding mode appears to be distinct from that of
      canonical coactivators such as NCoA/SRC/p160 family members. To elucidate the
      potentially unique molecular mechanism of PGC-1alpha recruitment, we have
      determined the crystal structure of HNF4alpha in complex with a fragment of PGC
      1alpha containing all three of its LXXLL motifs. Despite the presence of all
      three LXXLL motifs available for interactions, only one is bound at the canonical
      binding site, with no additional contacts observed between the two proteins.
      However, a close inspection of the electron density map indicates that the bound
      LXXLL motif is not a selected one but an averaged structure of more than one
      LXXLL motif. Further biochemical and functional studies show that the individual
      LXXLL motifs can bind but drive only minimal transactivation. Only when more than
      one LXXLL motif is involved can significant transcriptional activity be measured,
      and full activation requires all three LXXLL motifs. These findings led us to
      propose a model wherein each LXXLL motif has an additive effect, and the multiple
      binding modes by HNF4alpha toward the LXXLL motifs of PGC-1alpha could account
      for the apparent robust activation by providing a flexible mechanism for
      combinatorial recruitment of additional coactivators and mediators.

PMID- 19846558
TI  - Identification of Isn1 and Sdt1 as glucose- and vitamin-regulated nicotinamide
      mononucleotide and nicotinic acid mononucleotide [corrected] 5'-nucleotidases
      responsible for production of nicotinamide riboside and nicotinic acid riboside.
AB  - Recently, we discovered that nicotinamide riboside and nicotinic acid riboside
      are biosynthetic precursors of NAD(+), which are utilized through two pathways
      consisting of distinct enzymes. In addition, we have shown that exogenously
      supplied nicotinamide riboside is imported into yeast cells by a dedicated
      transporter, and it extends replicative lifespan on high glucose medium. Here, we
      show that nicotinamide riboside and nicotinic acid riboside are authentic
      intracellular metabolites in yeast. Secreted nicotinamide riboside was detected
      with a biological assay, and intracellular levels of nicotinamide riboside,
      nicotinic acid riboside, and other NAD(+) metabolites were determined by a liquid
      chromatography-mass spectrometry method. A biochemical genomic screen indicated
      that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase
      activity in vitro. Metabolic profiling of knock-out mutants established that Isn1
      and Sdt1 are responsible for production of nicotinamide riboside and nicotinic
      acid riboside in cells. Isn1, initially classified as an IMP-specific 5'
      nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are
      additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1
      overexpression is growth-inhibitory to cells in a manner that depends on its
      active site and correlates with reduced cellular NAD(+). Expression of Isn1
      protein is positively regulated by the availability of nicotinic acid and
      glucose. These results reveal unanticipated and highly regulated steps in NAD(+)
      metabolism.

PMID- 19846559
TI  - Transcription elongation complex stability: the topological lock.
AB  - Transcription machinery from a variety of organisms shows striking mechanistic
      similarity. Both multi- and single subunit RNA polymerases have evolved an 8-10
      base pair RNA-DNA hybrid as a part of a stably transcribing elongation complex.
      Through characterization of halted complexes that can readily carry out
      homopolymeric slippage synthesis, this study reveals that T7 RNA polymerase
      elongation complexes containing only a 4-base pair hybrid can nevertheless be
      more stable than those with the normal 8-base pair hybrid. We propose that a key
      feature of this stability is the topological threading of RNA through the complex
      and/or around the DNA template strand. The data are consistent with forward
      translocation as a mechanism to allow unthreading of the topological lock, as can
      occur during programmed termination of transcription.

PMID- 19846560
TI  - Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI
      17 family, C-kinase-activated PP1 inhibitors.
AB  - The regulatory circuit controlling cellular protein phosphatase-1 (PP1), an
      abundant group of Ser/Thr phosphatases, involves phosphorylation of PP1-specific
      inhibitor proteins. Malfunctions of these inhibitor proteins have been linked to
      a variety of diseases, including cardiovascular disease and cancer. Upon
      phosphorylation at Thr(38), the 17-kDa PP1 inhibitor protein, CPI-17, selectively
      inhibits a specific form of PP1, myosin light chain phosphatase, which transduces
      multiple kinase signals into the phosphorylation of myosin II and other proteins.
      Here, the mechanisms underlying PP1 inhibition and the kinase/PP1 cross-talk
      mediated by CPI-17 and its related proteins, PHI, KEPI, and GBPI, are discussed.

PMID- 19846561
TI  - Crystal structure of family 14 polysaccharide lyase with pH-dependent modes of
      action.
AB  - The Chlorella virus enzyme vAL-1 (38 kDa), a member of polysaccharide lyase
      family 14, degrades the Chlorella cell wall by cleaving the glycoside bond of the
      glucuronate residue (GlcA) through a beta-elimination reaction. The enzyme
      consists of an N-terminal cell wall-attaching domain (11 kDa) and a C-terminal
      catalytic module (27 kDa). Here, we show the enzyme characteristics of vAL-1,
      especially its pH-dependent modes of action, and determine the structure of the
      catalytic module. vAL-1 also exhibited alginate lyase activity at alkaline pH,
      and truncation of the N-terminal domain increased the lyase activity by 50-fold
      at pH 7.0. The truncated form vAL-1(S) released di- to hexasaccharides from
      alginate at pH 7.0, whereas disaccharides were preferentially generated at pH
      10.0. This indicates that vAL-1(S) shows two pH-dependent modes of action: endo-
      and exotypes. The x-ray crystal structure of vAL-1(S) at 1.2 A resolution showed
      two antiparallel beta-sheets with a deep cleft showing a beta-jelly roll fold.
      The structure of GlcA-bound vAL-1(S) at pH 7.0 and 10.0 was determined: GlcA was
      found to be bound outside and inside the cleft at pH 7.0 and 10.0, respectively.
      This suggests that the electric charges at the active site greatly influence the
      binding mode of substrates and regulate endo/exo activity. Site-directed
      mutagenesis demonstrated that vAL-1(S) has a specific amino acid arrangement
      distinct from other alginate lyases crucial for catalysis. This is, to our
      knowledge, the first study in which the structure of a family 14 polysaccharide
      lyase with two different modes of action has been determined.

PMID- 19846562
TI  - Velocity estimates for signal propagation leading to systemic jasmonic acid
      accumulation in wounded Arabidopsis.
AB  - The wound response prohormone jasmonic acid (JA) accumulates rapidly in tissues
      both proximal and distal to injury sites in plants. Using quantitative liquid
      chromatography-mass spectrometry after flash freezing of tissues, we found that
      JA accumulated within 30 s of injury in wounded Arabidopsis leaves (p = 3.5 e(
      7)). JA augmentation distal to wounds was strongest in unwounded leaves with
      direct vascular connections to wounded leaves wherein JA levels increased
      significantly within 120 s of wounding (p = 0.00027). This gave conservative and
      statistically robust temporal boundaries for the average velocity of the long
      distance signal leading to distal JA accumulation in unwounded leaves of 3.4-4.5
      cm min(-1). Like JA, transcripts of the JA synthesis gene LIPOXYGENASE2 (LOX2)
      and the jasmonate response gene JAZ10.3 also accumulated to higher levels in
      directly interconnected leaves than in indirectly connected leaves. JA
      accumulation in a lox2-1 mutant plant was initiated rapidly after wounding then
      slowed progressively compared with the wild type (WT). Despite this, JAZ10.3
      expression in the two genotypes was similar. Free cyclopentenone jasmonate levels
      were similar in both resting WT and lox2-1. In contrast, bound cyclopentenone
      jasmonates (arabidopsides) were far lower in lox2-1 than in the WT. The major
      roles of LOX2 are to generate arabidopsides and the large levels of JA that
      accumulate proximal to the wound. LOX2 is not essential for some of the most
      rapid events elicited by wounding.

PMID- 19846564
TI  - Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum
      lipids among adults living near a chemical plant.
AB  - Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are compounds
      that do not occur in nature but have been widely used since World War II and
      persist indefinitely in the environment. They are present in the serum of
      Americans with median levels of 4 ng/mL and 21 ng/mL, respectively. PFOA has been
      positively associated with cholesterol in several studies of workers. A cross
      sectional study of lipids and PFOA and PFOS was conducted among 46,294 community
      residents aged 18 years or above, who drank water contaminated with PFOA from a
      chemical plant in West Virginia. The mean levels of serum PFOA and PFOS in 2005
      2006 were 80 ng/mL (median, 27 ng/mL) and 22 ng/mL (median, 20 ng/mL),
      respectively. All lipid outcomes except high density lipoprotein cholesterol
      showed significant increasing trends by increasing decile of either compound;
      high density lipoprotein cholesterol showed no association. The predicted
      increase in cholesterol from lowest to highest decile for either compound was 11
      12 mg/dL. The odds ratios for high cholesterol (>/=240 mg/dL), by increasing
      quartile of PFOA, were 1.00, 1.21 (95% confidence interval (CI): 1.12, 1.31),
      1.33 (95% CI: 1.23, 1.43), and 1.40 (95% CI: 1.29, 1.51) and were similar for
      PFOS quartiles. Because these data are cross-sectional, causal inference is
      limited. Nonetheless, the associations between these compounds and lipids raise
      concerns, given their common presence in the general population.

PMID- 19846563
TI  - Mutant N143P reveals how Na+ activates thrombin.
AB  - The molecular mechanism of thrombin activation by Na(+) remains elusive. Its
      kinetic formulation requires extension of the classical Botts-Morales theory for
      the action of a modifier on an enzyme to correctly account for the contribution
      of the E*, E, and E:Na(+) forms. The extended scheme establishes that analysis of
      k(cat) unequivocally identifies allosteric transduction of Na(+) binding into
      enhanced catalytic activity. The thrombin mutant N143P features no Na(+)
      dependent enhancement of k(cat) yet binds Na(+) with an affinity comparable to
      that of wild type. Crystal structures of the mutant in the presence and absence
      of Na(+) confirm that Pro(143) abrogates the important H-bond between the
      backbone N atom of residue 143 and the carbonyl O atom of Glu(192), which in turn
      controls the orientation of the Glu(192)-Gly(193) peptide bond and the correct
      architecture of the oxyanion hole. We conclude that Na(+) activates thrombin by
      securing the correct orientation of the Glu(192)-Gly(193) peptide bond, which is
      likely flipped in the absence of cation. Absolute conservation of the 143-192 H
      bond in trypsin-like proteases and the importance of the oxyanion hole in
      protease function suggest that this mechanism of Na(+) activation is present in
      all Na(+)-activated trypsin-like proteases.

PMID- 19846565
TI  - Genetic variation in the progesterone receptor and metabolism pathways and
      hormone therapy in relation to breast cancer risk.
AB  - The relevance of progesterone to breast carcinogenesis is highlighted by evidence
      indicating that use of combined estrogen-progesterone therapy (EPT) is more
      strongly related to breast cancer risk than is use of unopposed estrogen therapy.
      However, few investigators have assessed how genetic variation in progesterone
      related genes modifies the effect of EPT on risk. In an analysis combining data
      from 2 population-based case-control studies of postmenopausal breast cancer
      (1,296 cases and 1,055 controls) conducted in Washington State in 1997-1999 and
      2000-2004, the authors evaluated how 51 single nucleotide polymorphisms in 7
      progesterone-related genes (AKR1C1, AKR1C2, AKR1C3, CYP3A4, SRD5A1, SRD5A2, and
      PGR) influenced breast cancer risk. There was no appreciable association with
      breast cancer risk overall for any single nucleotide polymorphism. For rs2854482
      in AKR1C2, carrying 1 or 2 A alleles was associated with a 2.0-fold increased
      breast cancer risk in EPT users (95% confidence interval: 1.0, 4.0) but not in
      never users (P(heterogeneity) = 0.03). For rs12387 in AKR1C3, the presence of 1
      or 2 G alleles was associated with a 1.5-fold increased risk among EPT users (95%
      confidence interval: 1.1, 2.2) but not in never users (P(heterogeneity) = 0.02).
      Interpretation of these subgroup associations must await the results of similar
      studies conducted in other populations.

PMID- 19846567
TI  - Towards reducing disparities in disparities research.

PMID- 19846566
TI  - Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR)
      C677T polymorphism and colorectal cancer: a HuGE-GSEC review.
AB  - Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002,
      with a 50% mortality rate, making CRC the second most common cancer in adults.
      Certain racial/ethnic populations continue to experience a disproportionate
      burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate
      reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors
      performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a
      pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR
      polymorphism and CRC, with stratification by racial/ethnic population and
      behavioral risk factors. There were few studies on different racial/ethnic
      populations. The overall meta-analysis odds ratio for CRC for persons with the TT
      genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse
      association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and
      Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks.
      Similar results were observed for Asians, Latinos, and blacks in the pooled
      analysis. The inverse association between the MTHFR 677TT polymorphism and CRC
      was not significantly modified by smoking status or body mass index; however, it
      was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to
      be associated with a reduced risk of CRC, but this may not hold true for all
      populations.

PMID- 19846568
TI  - Correlates of multiple chronic disease behavioral risk factors in Canadian
      children and adolescents.
AB  - The authors assessed individual, social, and school correlates of multiple
      chronic disease behavioral risk factors (physical inactivity, sedentary behavior,
      tobacco smoking, alcohol drinking, and high body mass index) in a representative
      sample of Canadian youth aged 10-15 years (mean = 12.5 years) attending public
      schools. Cross-sectional data (n = 1,747) from cycle 4 (2000-2001) of the
      National Longitudinal Survey of Children and Youth were used. Ordinal regression
      models were constructed to investigate associations between selected covariates
      and multiple behavioral risk-factor levels (0/1, 2, 3, or 4/5 risk factors).
      Older age (odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.21, 3.13),
      caregiver smoking (OR = 1.49, 95% CI: 1.09, 2.03), reporting that most/all of
      one's peers smoked (OR = 7.31, 95% CI: 4.00, 13.35) or drank alcohol (OR = 3.77,
      95% CI: 2.18, 6.53), and living in a lone-parent family (OR = 1.94, 95% CI: 1.31,
      2.88) increased the likelihood of having multiple behavioral risk factors. Youth
      with high self-esteem (OR = 0.92, 95% CI: 0.85, 0.99) and youth from families
      with postsecondary education (OR = 0.58, 95% CI: 0.41, 0.82) were less likely to
      have a higher number of risk factors. Although several individual and social
      characteristics were associated with multiple behavioral risk factors, no school
      related correlates emerged. These variables should be considered when planning
      prevention programs.

PMID- 19846569
TI  - Major role for ACE-independent intrarenal ANG II formation in type II diabetes.
AB  - Combination therapy of angiotensin-converting enzyme (ACE) inhibition and AT(1)
      receptor blockade has been shown to provide greater renoprotection than ACE
      inhibitor alone in human diabetic nephropathy, suggesting that ACE-independent
      pathways for ANG II formation are of major significance in disease progression.
      Studies were performed to determine the magnitude of intrarenal ACE-independent
      formation of ANG II in type II diabetes. Although renal cortical ACE protein
      activity [2.1 +/- 0.8 vs. 9.2 +/- 2.1 arbitrary fluorescence units (AFU) x mg(-1)
      x min(-1)] and intensity of immunohistochemical staining were significantly
      reduced and ACE2 protein activity (16.7 +/- 3.2 vs. 7.2 +/- 2.4 AFU x mg(-1) x
      min(-1)) and intensity elevated, kidney ANG I (113 +/- 24 vs. 110 +/- 45 fmol/g)
      and ANG II (1,017 +/- 165 vs. 788 +/- 99 fmol/g) levels were not different
      between diabetic and control mice. Afferent arteriole vasoconstriction due to
      conversion of ANG I to ANG II was similar in magnitude in kidneys of diabetic (
      28 +/- 3% at 1 microM) and control (-23 +/- 3% at 1 microM) mice; a response
      completely inhibited by AT(1) receptor blockade. In control kidneys, afferent
      arteriole vasoconstriction produced by ANG I was significantly attenuated by ACE
      inhibition, but not by serine protease inhibition. In contrast, afferent
      arteriole vasoconstriction produced by intrarenal conversion of ANG I to ANG II
      was significantly attenuated by serine protease inhibition, but not by ACE
      inhibition in diabetic kidneys. In conclusion, there is a switch from ACE
      dependent to serine protease-dependent ANG II formation in the type II diabetic
      kidney. Pharmacological targeting of these serine protease-dependent pathways may
      provide further protection from diabetic renal vascular disease.

PMID- 19846570
TI  - Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and
      ACE inhibition.
AB  - Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development
      of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To
      determine if these effects are associated with changes in the mouse intrarenal
      renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE,
      angiotensin type 1 receptor (AT(1)R) mRNA (by quanitative RT-PCR) and protein [by
      Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male
      mice (9-12 wk old) were distributed as controls (n = 10), ANG II infused (ANG II
      = 8, 400 ng x kg(-1) x min(-1) for 12 days), ACEi only (ACEi = 10, lisinopril,
      100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with
      controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 +/- 0.13, P <
      0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 +/- 0.14, P <
      0.05). ACE protein (by WB) was increased by ANG II (1.21 +/- 0.08, P < 0.05), and
      it was reduced by ACEi alone (0.88 +/- 0.07, P < 0.05) or in combination with ANG
      II (0.80 +/- 0.07, P < 0.05). AT(1)R protein (by WB) was increased by ANG II
      (1.27 +/- 0.06, P < 0.05) and ACEi (1.17 +/- 0.06, P < 0.05) but not ANG II +
      ACEi [1.15 +/- 0.06, not significant (NS)]. Tubular renin protein (semiquantified
      by IHC) was increased by ANG II (1.49 +/- 0.23, P < 0.05) and ACEi (1.57 +/-
      0.15, P < 0.05), but not ANG II + ACEi (1.10 +/- 0.15, NS). No significant
      changes were observed in AGT, ACE, or AT(1)R mRNA. In summary, reduced responses
      of intrarenal tubular renin, ACE, and the AT(1)R protein to the stimulatory
      effects of chronic ANG II infusions, in the presence of ACEi, are associated with
      the effects of this treatment to ameliorate augmentations in blood pressure and
      intrarenal ANG II content during ANG II-induced hypertension.

PMID- 19846571
TI  - Noncanonical TGF-beta pathways, mTORC1 and Abl, in renal interstitial
      fibrogenesis.
AB  - Renal interstitial fibrosis is a major determinant of renal failure in the
      majority of chronic renal diseases. Transforming growth factor-beta (TGF-beta) is
      the single most important cytokine promoting renal fibrogenesis. Recent in vitro
      studies identified novel non-smad TGF-beta targets including p21-activated kinase
      2 (PAK2), the abelson nonreceptor tyrosine kinase (c-Abl), and the mammalian
      target of rapamycin (mTOR) that are activated by TGF-beta in mesenchymal cells,
      specifically in fibroblasts but less in epithelial cells. In the present studies,
      we show that non-smad effectors of TGF-beta including PAK2, c-Abl, Akt, tuberin
      (TSC2), and mTOR are activated in experimental unilateral obstructive nephropathy
      in rats. Treatment with c-Abl or mTOR inhibitors, imatinib mesylate and
      rapamycin, respectively, each blocks noncanonical (non-smad) TGF-beta pathways in
      the kidney in vivo and diminishes the number of interstitial fibroblasts and
      myofibroblasts as well as the interstitial accumulation of extracellular matrix
      proteins. These findings indicate that noncanonical TGF-beta pathways are
      activated during the early and rapid renal fibrogenesis of obstructive
      nephropathy. Moreover, the current findings suggest that combined inhibition of
      key regulators of these non-smad TGF-beta pathways even in dose-sparing protocols
      are effective treatments in renal fibrogenesis.

PMID- 19846572
TI  - Size and conformation of Ficoll as determined by size-exclusion chromatography
      followed by multiangle light scattering.
AB  - The characteristics of the glomerular filtration barrier (GFB) are challenging to
      measure, as macromolecular solutes in blood may be metabolized or transported by
      various cells in the kidney. Urinary solute concentrations generally reflect the
      cumulative influence of multiple transport processes rather than the intrinsic
      behavior of the GFB alone. Synthetic tracer molecules which are not secreted,
      absorbed, or modified by the kidney are useful tools. Ficoll, a globular polymer
      of epichlorohydrin and sucrose, is round, physiologically inert, and easily
      labeled, making it a nearly ideal glomerular probe. Fissell et al. reported
      filtration data suggesting that Ficoll was not as spherical as had been
      previously suggested (Fissell WH, Manley S, Dubnisheva A, Glass J, Magistrelli J,
      Eldridge AN, Fleischman AJ, Zydney AL, Roy S. Am J Physiol Renal Physiol 293:
      F1209-F1213, 2007). More recently, two investigators published comparisons of
      neutral and anionic Ficoll clearance that suggest Ficoll may undergo
      conformational changes when chemically derivatized (Asgeirsson D, Venturoli D,
      Rippe B, Rippe C. Am J Physiol Renal Physiol 291: F1083-F1089, 2006; Guimaraes
      MAM, Nikolovski J, Pratt LM, Greive K, Comper WD. Am J Physiol Renal Physiol 285:
      F1118-F1124, 2003). To investigate Ficoll's characteristics further, we examined
      two commercial preparations, Ficoll 70 and Ficoll 400, by size-exclusion
      chromatography using a differential refractive index detector combined with light
      scattering and viscosity detectors. A slope of 0.45 was obtained from the plot of
      the logarithm of molecular mass against the logarithm of root-mean square radius.
      The Mark-Houwink exponent values of 0.34 and 0.36 were calculated for Ficoll 70
      and Ficoll 400, respectively. These results suggest Ficoll's conformation in
      physiological saline solution is likely intermediate between a solid sphere and a
      well-solvated linear random coil. The measurements help explain our previous
      observations and guide interpretation of in vivo experiments.

PMID- 19846573
TI  - ERK5 activation enhances mesangial cell viability and collagen matrix
      accumulation in rat progressive glomerulonephritis.
AB  - The mitogen-activated protein kinase (MAPK) cascade plays an important role in
      the regulation of various cellular functions in glomerulonephritis (GN). Here, we
      investigated whether extracellular signal-regulated kinase 5 (ERK5), a member of
      the MAPK family, is involved in the pathogenesis of chronic mesangioproliferative
      GN, using a rat model induced by uninephrectomy and anti-Thy-1 antibody
      injection. Immunostaining of kidneys obtained at different time points revealed
      that phospho-ERK5 was weakly expressed in control glomeruli but dramatically
      increased in a typical mesangial pattern after 28 and 56 days of GN. A
      semiquantitative assessment indicated that glomerular phospho-ERK5 expression
      closely paralleled the accumulation of extracellular matrix (ECM), collagen type
      I, as well as glomerular expression of reactive oxygen species (ROS) and ANG II.
      On the other hand, phospho-ERK1/2 expression increased on day 7 during the phase
      of enhanced mesangial cell (MC) proliferation and decreased thereafter. H(2)O(2)
      and ANG II each induced ERK5 phosphorylation by cultured rat MCs. Costimulation
      with both H(2)O(2) and ANG II synergistically increased ERK5 phosphorylation in
      MCs. Cultured MCs transfected with ERK5-specific small interference RNA showed a
      significant decrease in H(2)O(2) or ANG II-induced cell viability and soluble
      collagen secretion compared with control cells. Treatment of GN rats with an ANG
      II type 1 receptor blocker resulted in significant decreases in phospho-ERK5
      expression and collagen accumulation accompanied by remarkable histological
      improvement. Taken together, these results suggest that MC ERK5 phosphorylation
      by ANG II or H(2)O(2) enhances cell viability and ECM accumulation in an
      experimental model of chronic GN.

PMID- 19846574
TI  - Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombin.
AB  - Thrombin is a multifunctional protease that plays a key role in hemostasis,
      thrombosis, and inflammation. Most thrombin inhibitors currently used as
      antithrombotic agents target thrombin's active site and inhibit all of its myriad
      of activities. Exosites 1 and 2 are distinct regions on the surface of thrombin
      that provide specificity to its proteolytic activity by mediating binding to
      substrates, receptors, and cofactors. Exosite 1 mediates binding and cleavage of
      fibrinogen, proteolytically activated receptors, and some coagulation factors,
      while exosite 2 mediates binding to heparin and to platelet receptor GPIb-IX-V.
      The crystal structures of two nucleic acid ligands bound to thrombin have been
      solved. Previously Padmanabhan and colleagues solved the structure of a DNA
      aptamer bound to exosite 1 and we reported the structure of an RNA aptamer bound
      to exosite 2 on thrombin. Based upon these structural studies we speculated that
      the two aptamers would not compete for binding to thrombin. We observe that
      simultaneously blocking both exosites with the aptamers leads to synergistic
      inhibition of thrombin-dependent platelet activation and procoagulant activity.
      This combination of exosite 1 and exosite 2 inhibitors may provide a particularly
      effective antithrombotic approach.

PMID- 19846575
TI  - A prospective open-label study of mycophenolate mofetil for the treatment of
      diffuse systemic sclerosis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil for the
      treatment of SSc. METHODS: We recruited 15 patients with dcSSc to take part in an
      open-label study using mycophenolate mofetil to treat their disease over a 12
      month period. The primary outcome measure was the modified Rodnan skin score
      (mRSS), whereas secondary outcomes included the Medsger severity score, pulmonary
      function studies, 2D echocardiograms and the Short Form Health Survey (SF)-36
      questionnaire. RESULTS: The mRSS significantly improved in those patients who
      tolerated the medication for >3 months (P < 0.0001), and there was a
      statistically significant improvement in the Medsger severity scores of the
      general (P = 0.05), peripheral vascular involvement (P = 0.05) and skin (P =
      0.0003) scores. The SF-36 scores improved (P = 0.05) and the pulmonary function
      studies showed a trend towards improvement, though not of statistical
      significance. The mean pulmonary artery pressure by 2D echocardiography did not
      change. CONCLUSIONS: In this prospective open-label study of mycophenolate
      mofetil for the treatment of dcSSc, we observed significant improvements in skin
      scores, peripheral vascular involvement and patient-perceived health status.
      Pulmonary function studies did not worsen as expected, but instead showed a trend
      towards improvement. Controlled trials are needed to further investigate this
      trend for improved pulmonary function studies.

PMID- 19846576
TI  - Trifascicular block and a raised Troponin 'T' in acute cholecystitis.

PMID- 19846577
TI  - Sick patient, normal tests.

PMID- 19846578
TI  - The long road of biopharmaceutical drug development: from inception to marketing.
AB  - The development of therapeutics is costly, time-consuming and has high attrition
      rates. Biopharmaceutical medications differ from traditional agents in their
      discovery, design, structure and formulation. Prior to marketing a drug must show
      efficacy and acceptable toxicity in both preclinical and clinical trials.
      Regulatory bodies have a pivotal role in the licensing, naming and marketing of
      an agent.

PMID- 19846579
TI  - An improved medical admissions risk system using multivariable fractional
      polynomial logistic regression modelling.
AB  - AIM: To develop and validate an in-hospital mortality risk prediction tool for
      unselected acutely ill medical patients using routinely collected physiological
      and laboratory data. DESIGN: Analysis of all emergency medical patients admitted
      to St James's Hospital (SJH), Dublin, between 1 January 2002 and 31 December
      2007. Validation using a dataset of acute medical admissions from Nenagh Hospital
      2000-04. METHODS: Using routinely collected vital signs and laboratory findings,
      a composite 5-day in-hospital mortality risk score, designated medical admissions
      risk system (MARS), was developed using an iterative approach involving logistic
      regression and multivariable fractional polynomials. Results are presented as
      area under receiver operating characteristics curves (AUROC) as well as Hosmer
      and Lemeshow goodness-of-fit statistics. RESULTS: A total of 10 712 and 3597
      unique patients were admitted to SJH and Nenagh Hospital, respectively. The final
      score included nine variables [age, heart rate, mean arterial pressure,
      respiratory rate, temperature, urea, potassium (K), haematocrit and white cell
      count]. The AUROC for 5-day in-hospital mortality was 0.93 [95% confidence
      interval (CI) 0.92-0.94] for the SJH cohort (Hosmer and Lemeshow test, P = 0.32)
      and 0.92 (95% CI 0.90-0.94) for the external Nenagh hospital validation cohort
      (Hosmer and Lemeshow test, P = 0.28). CONCLUSION: In-hospital mortality
      estimation using only routinely collected emergency department admission data is
      possible in unselected acute medical patients using the MARS system. Such a score
      applied to acute medical patients at the time of admission, could assist senior
      clinical decision makers in promptly and accurately focusing limited clinical
      resources. Further studies validating the impact of this model on clinical
      outcomes are warranted.

PMID- 19846580
TI  - Comparison of the substrate specificities and catalytic properties of the sister
      N-acetylglucosaminyltransferases, GnT-V and GnT-Vb (IX).
AB  - N-Acetylglucosaminlyltransferase-V (GnT-V) synthesizes GlcNAcbeta1,6Man branched
      N-glycans both in vitro and in vivo. A paralog, GnT-Vb (or GnT-IX), has also been
      shown to synthesize both GlcNAcbeta1,6Man branched N- and O-glycans. GnT-V is
      expressed in most human and rodent tissues while GnT-Vb expression is limited
      mainly to neural tissue and testes. It is of interest, therefore, to compare the
      catalytic properties and reaction kinetics of these sister enzymes. The results
      demonstrate that while GnT-V was fully active without exogenous cation and in the
      presence of EDTA, the activity of GnT-Vb was stimulated over 4-fold in the
      presence of 10 mM Mn(++). The pH optimum for GnT-V was in the range of 6.5-7.0,
      while that of GnT-Vb was 8.0. common for glycosyltransferases active in brain.
      Both enzymes transferred GlcNAcbeta1,6 to the Man residue of the GlcNAcbeta1,2Man
      moiety of glycan substrates, and both enzymes acted effectively on a synthetic
      GlcNAcbeta1,2Manalpha1,2Glc-O-octyl trisaccharide acceptor. Moreover, although
      both enzymes utilized an N-linked asialo-agalacto-biantennary glycan as an
      acceptor, GnT-Vb displayed an almost 2.5-fold higher apparent K(m) value compared
      to GnT-V. Conversely, GnT-Vb very efficiently glycosylated a synthetic
      glycopeptide, Ac-H(2)N-Val-Glu-Pro-(GlcNAcbeta1,2-Man-O-)Thr-Ala-Val-CO-Ac, while
      GnT-V showed relatively poor activity toward this O-Man-linked glycopeptide
      acceptor, with a K(m) value of 20-fold higher than that of GnT-Vb. When the N
      linked asialo-agalacto-biantennary glycan acceptor was utilized with GnT-Vb, the
      expected triantennary beta1,6-branched product was observed up to 8 h incubation.
      An additional product with two beta1,6-linked GlcNAc resides, however, was
      observed after prolonged (>8 h) incubation, consistent with an earlier report.
      This unusual tetraantennary product was observed with GnT-Vb only after
      substantial accumulation of the first triantennary product and not during the
      early stages of incubation.

PMID- 19846581
TI  - Brief report: mothers' long-term posttraumatic stress symptoms following a burn
      event of their child.
AB  - OBJECTIVE: This prospective longitudinal study examines the course of
      posttraumatic stress symptoms (PTSS) in mothers of children with burns between 1
      and 11 years after the burn event and the role of burn severity and feelings of
      guilt on this course. METHOD: Self-reported PTSS of 48 mothers were measured with
      the Impact of Event Scale. Guilt feelings were assessed during an in-depth
      interview 2 years after the burn event. Eleven years after the burn event,
      mothers marked their child's scars at the present time on a drawing. RESULTS:
      Over a period of 10 years, maternal PTSS decreased. Multiple regression analysis
      showed that the interaction between guilt and burn severity predicted the course
      of PTSS. CONCLUSIONS: Although PTSS substantially decreases through the years, a
      subset of mothers, in particular mothers who feel guilty about the burn event and
      whose children have more extensive permanent scarring seem at risk for longer
      term PTSS.

PMID- 19846583
TI  - Unilateral pedunculopontine stimulation improves falls in Parkinson's disease.
AB  - Postural instability and falls are a major source of disability in patients with
      advanced Parkinson's disease. These problems are currently not well addressed by
      either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery.
      The neuroanatomical substrates of posture and gait are poorly understood but a
      number of important observations suggest a major role for the pedunculopontine
      nucleus and adjacent areas in the brainstem. We conducted a double-blinded
      evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a
      pilot study in six advanced Parkinson's disease patients with significant gait
      and postural abnormalities. There was no significant difference in the double
      blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor
      scores after 3 or 12 months of continuous stimulation and no improvements in the
      Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In
      contrast, patients reported a significant reduction in falls in the on and off
      medication states both at 3 and 12 months after pedunculopontine nucleus deep
      brain stimulation as captured in the Unified Parkinson's Disease Rating Scale
      part II scores. Our results suggest that pedunculopontine nucleus deep-brain
      stimulation may be effective in preventing falls in patients with advanced
      Parkinson's disease but that further evaluation of this procedure is required.

PMID- 19846582
TI  - Clinical features of spinal and bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by
      a CAG repeat expansion in the androgen receptor gene. To characterize the natural
      history and define outcome measures for clinical trials, we assessed the clinical
      history, laboratory findings and muscle strength and function in 57 patients with
      genetically confirmed disease. We also administered self-assessment
      questionnaires for activities of daily living, quality of life and erectile
      function. We found an average delay of over 5 years from onset of weakness to
      diagnosis. Muscle strength and function correlated directly with serum
      testosterone levels and inversely with CAG repeat length, age and duration of
      weakness. Motor unit number estimation was decreased by about half compared to
      healthy controls. Sensory nerve action potentials were reduced in nearly all
      subjects. Quantitative muscle assessment and timed 2 min walk may be useful as
      meaningful indicators of disease status. The direct correlation of testosterone
      levels with muscle strength indicates that androgens may have a positive effect
      on muscle function in spinal and bulbar muscular atrophy patients, in addition to
      the toxic effects described in animal models.

PMID- 19846584
TI  - Introduction: gendering socio cultural alcohol and drug research.
AB  - AIM: The gender gap in alcohol consumption and alcohol-related harm still is
      considerable and largely unexplained. This paper introduces four studies
      performed in Sweden that explore factors influencing gender differences in levels
      of consumption, adverse consequences and treatment. METHOD: We summarize and
      discuss these four studies performed within the same cultural setting, which each
      analyse interaction with the gender. RESULTS: Two studies focus on the individual
      level addressing criminal behaviour, alcohol problems and mortality, and gender
      identity and alcohol problems in women taking psychiatric co-morbidity into
      account. Two studies focus on the institutional and cultural levels addressing
      the handling of alcohol-related problems in primary healthcare and the
      effectiveness of using cultural analysis in identifying gender concerns for
      women. CONCLUSION: Future studies need to focus more on these complex
      associations to secure that treatment settings provide both genders with fair and
      adequate treatment of high quality and that prevention activities will start to
      test measures that take gender into consideration.

PMID- 19846585
TI  - Does gender matter? A vignette study of general practitioners' management skills
      in handling patients with alcohol-related problems.
AB  - AIMS: The aims of this study were to analyse the perceptions of female and male
      primary care physicians (PCPs) of alcohol problems in male and female patients,
      their recommendations to reduce or abstain from alcohol, their referrals to
      treatment and their views of safe levels of drinking for male and female
      patients. These factors were related to the physicians' own alcohol consumption.
      METHODS: A slightly adjusted version of the WHO Collaborative Study Questionnaire
      for General Practitioners was posted to all PCPs (n = 132) in the district of
      Skaraborg, Sweden, of whom 68 PCPs responded. In the questionnaire, the PCPs'
      perceptions of two patient vignettes were analysed. RESULTS: Both the gender of
      the patients in the vignettes and of the PCPs influenced the advice and the
      referrals that the patients received: 83% of male excessive drinkers and 47% of
      female excessive drinkers were recommended to cut down on drinking. In 50% of
      cases, the male excessive drinker was not referred, compared with 25% for the
      female excessive drinker. This was statistically significant only for excessive
      drinkers. The odds ratio for referral to any treatment was 0.33 (CI = 0.12-0.93)
      for the male excessive drinker compared with the female excessive drinker. The
      male PCP referred the excessive drinker less often to any treatment than did the
      female PCP, odds ratio 0.26 (CI = 0.08-0.90). The upper limit of alcohol
      consumption before the PCPs would advise the patient to cut down was
      significantly higher for PCPs with the AUDIT-C score >or= 3. The limit was 146
      g/week for male patients and 103 g/week for female patients. Corresponding
      figures for PCP with the AUDIT-C score <or= 2 were 89 and 68 g/week. CONCLUSION:
      Male patients were less likely to be advised to stop drinking altogether than
      female patients and were less likely to be referred, according to this vignette
      study. Taking into account that male patients have a higher prevalence of alcohol
      problems, this may be of considerable importance for men's health outcomes.
      Implications of these findings are the need to increase awareness of male
      excessive drinking and that gendered perceptions might bias alcohol management
      recommendations.

PMID- 19846586
TI  - Lack of leadership confidence relates to problem drinking in women: gender
      identity, heavy episodic drinking and alcohol use disorders in Swedish women.
AB  - AIM: The aim of this study was to analyse in women the association between four
      dimensions of gender identity, heavy episodic drinking (HED) and alcohol use
      disorders (AUD), taking into account age, personality, psychiatric co-morbidity
      and level of education. METHODS: An initial screening of alcohol consumption was
      followed by a structured psychiatric interview in a sample of women drawn from
      the Gothenburg population and women attending primary care, maternity and
      hospital services (n = 930). Gender identity was assessed using the Masculinity
      Femininity Questionnaire (M/F-Q) (items grouped into four dimensions: leadership,
      caring, self-assertiveness and emotionality). The Karolinska Scale of Personality
      was administered. Clinical psychiatric diagnoses according to DSM were made in
      face-to-face interviews. HED was defined as consumption of at least 60 g of
      ethanol on a single day at least once a month. RESULTS: Women who scored low on
      the leadership dimension were twice as likely to have AUD [age-adjusted odds1.98
      (95% confidence interval 1.30-3.01)] compared to those with medium scores. These
      odds ratios were significant after adjustment for personality [2.21 (1.35-3.63)],
      psychiatric disorders [2.09 (1.25-3.47)] and level of education [1.95 (1.17
      3.26)]. Low scores on the leadership dimension were associated with HED [1.55
      (0.98-2.44)] after adjustment for age, personality, psychiatric disorders and
      level of education. High scores on leadership were not significantly associated
      with AUD or HED after these adjustments. The odds ratios for those who scored low
      on caring were non-significant throughout the analyses of associations with both
      AUD and HED. A similar pattern was found for the self-assertiveness dimension.
      Low emotionality was associated with decreased odds for AUD [0.42 (0.25-0.70)]
      and HED [0.66 (0.44-0.99)], and increased odds for AUD [2.14 (1.38-3.31)] and HED
      [2.33 (1.58-3.44)], after adjusting for age. These associations became non
      significant after adjustment for personality and remained so after psychiatric
      disorders and level of education were added to the models. CONCLUSION: Of the
      four gender identity dimensions, only low scores on leadership remained
      significantly associated with AUD and HED after adjustment for age and
      personality. Clinical work could focus on the development of leadership abilities
      in women scoring low on these items to improve the ability.

PMID- 19846587
TI  - Biomarkers for detecting thiamine deficiency--improving confidence and taking a
      comprehensive history are also important.

PMID- 19846588
TI  - Inhibition of delayed-type hypersensitivity by Cucurbitacin R through the curbing
      of lymphocyte proliferation and cytokine expression by means of nuclear factor AT
      translocation to the nucleus.
AB  - Cucurbitacin R is known to exhibit an anti-inflammatory effect in different
      experimental models of inflammation. In this article, we outline the effect of
      cucurbitacin R on T lymphocyte proliferation, cytokine production, and nuclear
      factor activation, as well as its influence on various experimental models of
      delayed-type hypersensitivity (DTH) in mice. Cucurbitacin R reduced the
      proliferation of phytohemagglutinin A-stimulated human T lymphocytes (IC(50), 18
      microM), modifying the cell cycle, as well as the production of cytokines
      [interleukin (IL)-2, IL-4, IL-10, and especially interferon-gamma] and the
      induction of the principal cyclins implicated in the cell cycle (A(1), B(1),
      D(2), and E). These effects are brought on by a novel, selective inhibition of
      nuclear factor AT (NFAT) by cucurbitacin R, with no concomitant effect on other
      transcription factors such as activator protein-1. In addition, we tested the in
      vivo effects of cucurbitacin R in three experimental models of DTH, as well as
      its effects on T lymphocyte proliferation, the cell cycle, cytokines, and
      cyclins. Although cucurbitacin R was found to reduce the inflammatory response
      brought on by both oxazolone and dinitrofluorobenzene, its activity was even more
      pronounced against sheep red blood cell-induced edema in mouse paws, with a clear
      reduction in the production of IL-1beta, IL-4, and tumor necrosis factor alpha in
      the inflamed paw. In conclusion, cucurbitacin R has the potential to be a new
      immunosuppressive agent with antiproliferative effects through the inhibition of
      the NFAT with anti-inflammatory activity in DTH reactions.

PMID- 19846589
TI  - Neurotransmitters and energy metabolites in amyloid-bearing APP(SWE)xPSEN1dE9
      Mouse Brain.
AB  - Alzheimer's disease is characterized by amyloid peptide formation and deposition,
      neurofibrillary tangles, synaptic loss and central cholinergic dysfunction,
      dysfunction of energy metabolism, and dementia; however, the interactions between
      these hallmarks remain poorly defined. We studied a well characterized mouse
      model of amyloid deposition, the doubly transgenic APP(SWE)xPSEN1dE9 mouse. At 10
      to 14 months of age, these mice had high levels of amyloid peptides (6.6 microg/g
      wet weight) and widespread amyloid plaques. Extracellular levels of acetylcholine
      (ACh) were determined by microdialysis in the hippocampus and were comparable
      with nontransgenic mice from the same colony. In the open field, both mouse
      strains responded with a 3-fold increase of hippocampal ACh release. Exploratory
      behavior of the transgenic mice appeared normal. Infusion of scopolamine evoked 5
      to 6-fold increases of ACh levels in both mouse strains. High-affinity choline
      uptake and cholinesterase activities were identical in both mouse lines.
      Extracellular levels of glucose and glycerol were similar in control and
      transgenic mice, whereas lactate levels were slightly (p = 0.06) and glutamate
      levels significantly (p = 0.02) lower in transgenic mice. Exploration caused
      increases of glucose and lactate, whereas infusion of scopolamine (1 microM)
      increased glucose but not lactate. Glutamate levels were increased by
      scopolamine, whereas glycerol remained constant under all the conditions. We
      conclude that amyloid peptide production and plaque deposition causes minor
      changes in cholinergic function and energy metabolites in transgenic mice in
      vivo. Amyloid peptide formation and/or deposition may not be sufficient for long
      term cholinergic or metabolic dysfunction.

PMID- 19846590
TI  - Lipoxin A(4) reduces lipopolysaccharide-induced inflammation in macrophages and
      intestinal epithelial cells through inhibition of nuclear factor-kappaB
      activation.
AB  - Lipoxins, which are bioactive lipids derived from omega-6 polyunsaturated fatty
      acids, play important roles in various biological functions. In this study, the
      anti-inflammatory effects of lipoxin A(4) (LXA4; 5S,6R,15S-trihydroxy-7,9,13
      trans-11-eicosatetraenoic acid) were investigated in in vitro cultured cell
      experiments and in vivo animal experiments. In mouse peritoneal macrophages and
      mouse macrophage cell line RAW264.7 cells, LXA4 reduced the lipopolysaccharide
      (LPS)-induced increase in the mRNA expression level of tumor necrosis factor
      (TNF)-alpha. LXA4 also reduced the LPS-induced nuclear translocation of nuclear
      factor-kappaB (NF-kappaB). In an LPS-induced acute inflammation mouse model, the
      injection of LXA4 at 5 microg/kg b.wt. led to down-regulation of the TNF-alpha
      level in serum and the TNF-alpha mRNA expression level in intestinal epithelial
      cells. Moreover, LXA4 reduced the LPS-caused phosphorylation of IkappaB kinases,
      IkappaB, and NF-kappaB, the degradation of IkappaB, and the nuclear translocation
      of NF-kappaB in intestinal epithelial cells. In a coculture system using RAW264.7
      cells and human colon carcinoma cell line Caco-2 cells, treatment with LXA4 to
      Caco-2 cells led to reduction of LPS-evoked TNF-alpha production in RAW264.7
      cells and interleukin-8 mRNA expression in Caco-2 cells. These results indicate
      that LXA4 exerts anti-inflammatory effects through inhibition of NF-kappaB
      activation, and, therefore, LXA4 may be useful as a therapeutic strategy against
      intestinal mucosa inflammation.

PMID- 19846591
TI  - Inflammation gender differences in heart disease patients.

PMID- 19846592
TI  - Environmental contributions to disparities in pregnancy outcomes.
AB  - One of the most persistent disparities in American health status is the
      pronounced difference in birth outcomes between non-Hispanic black and non
      Hispanic white women. Poor pregnancy outcomes have a substantial impact on
      mortality, morbidity, and health care costs. Increasing evidence indicates that
      environmental exposures are associated with poor birth outcomes. This paper
      reviews the latest research on how environmental exposures affect pregnancy
      outcomes and then discusses how these exposures may be embedded within a context
      of significant social and host factor stress. The analysis suggests that
      environmental, social, and host factors are cumulatively stressing non-Hispanic
      black women and that this cumulative stress may be a cause of the persistent
      disparities in pregnancy outcomes.

PMID- 19846593
TI  - REBASE--a database for DNA restriction and modification: enzymes, genes and
      genomes.
AB  - REBASE is a comprehensive database of information about restriction enzymes, DNA
      methyltransferases and related proteins involved in the biological process of
      restriction-modification (R-M). It contains fully referenced information about
      recognition and cleavage sites, isoschizomers, neoschizomers, commercial
      availability, methylation sensitivity, crystal and sequence data. Experimentally
      characterized homing endonucleases are also included. The fastest growing segment
      of REBASE contains the putative R-M systems found in the sequence databases.
      Comprehensive descriptions of the R-M content of all fully sequenced genomes are
      available including summary schematics. The contents of REBASE may be browsed
      from the web (http://rebase.neb.com) and selected compilations can be downloaded
      by ftp (ftp.neb.com). Additionally, monthly updates can be requested via email.

PMID- 19846594
TI  - Transcriptome profiling defines a novel regulon modulated by the LysR-type
      transcriptional regulator MexT in Pseudomonas aeruginosa.
AB  - The LysR-family regulator MexT modulates the expression of the MexEF-OprN efflux
      system in the human pathogen Pseudomonas aeruginosa. Recently, we demonstrated
      that MexT regulates certain virulence phenotypes, including the type-three
      secretion system and early attachment independent of its role in regulating MexEF
      OprN. In this study, transcriptome profiling was utilized to investigate the
      global nature of MexT regulation in P. aeruginosa PAO1 and an isogenic mexEF
      mutant. Twelve genes of unknown function were highly induced by overexpressing
      MexT independent of MexEF-OprN. A well-conserved DNA motif was identified in the
      upstream regulatory region of nine of these genes and upstream of mexE. Reporter
      fusion analysis demonstrated that the expression of the genes was significantly
      induced by MexT in P. aeruginosa and a heterogenous Escherichia coli strain and
      that the conserved sequence was required for this induction. The conserved DNA
      motif was further characterized as the MexT binding site by site-directed
      mutagenesis and electrophoretic mobility shift assays. Genes containing this
      conserved regulatory sequence were identified across other Pseudomonas species,
      and their expression was activated by MexT. Thus, a novel regulon directly
      modulated by MexT, that includes but is independent of mexEF-oprN, has been
      identified.

PMID- 19846595
TI  - Novel recognition motifs and biological functions of the RNA-binding protein HuD
      revealed by genome-wide identification of its targets.
AB  - HuD is a neuronal ELAV-like RNA-binding protein (RBP) involved in nervous system
      development, regeneration, and learning and memory. This protein stabilizes mRNAs
      by binding to AU-rich instability elements (AREs) in their 3' unstranslated
      regions (3' UTR). To isolate its in vivo targets, messenger ribonucleoprotein
      (mRNP) complexes containing HuD were first immunoprecipitated from brain extracts
      and directly bound mRNAs identified by subsequent GST-HuD pull downs and
      microarray assays. Using the 3' UTR sequences of the most enriched targets and
      the known sequence restrictions of the HuD ARE-binding site, we discovered three
      novel recognition motifs. Motifs 2 and 3 are U-rich whereas motif 1 is C-rich. In
      vitro binding assays indicated that HuD binds motif 3 with the highest affinity,
      followed by motifs 2 and 1, with less affinity. These motifs were found to be
      over-represented in brain mRNAs that are upregulated in HuD overexpressor mice,
      supporting the biological function of these sequences. Gene ontology analyses
      revealed that HuD targets are enriched in signaling pathways involved in neuronal
      differentiation and that many of these mRNAs encode other RBPs, translation
      factors and actin-binding proteins. These findings provide further insights into
      the post-transcriptional mechanisms by which HuD promotes neural development and
      synaptic plasticity.

PMID- 19846596
TI  - Selection of hyperfunctional siRNAs with improved potency and specificity.
AB  - One critical step in RNA interference (RNAi) experiments is to design small
      interfering RNAs (siRNAs) that can greatly reduce the expression of the target
      transcripts, but not of other unintended targets. Although various statistical
      and computational approaches have been attempted, this remains a challenge facing
      RNAi researchers. Here, we present a new experimentally validated method for
      siRNA design. By analyzing public siRNA data and focusing on hyperfunctional
      siRNAs, we identified a set of sequence features as potency selection criteria to
      build an siRNA design algorithm with support vector machines. Additional
      bioinformatics filters were also included in the algorithm to increase RNAi
      specificity by reducing potential sequence cross-hybridization or microRNA-like
      effects. Independent validation experiments were performed, which indicated that
      the newly designed siRNAs have significantly improved performance, and worked
      effectively even at low concentrations. Furthermore, our cell-based studies
      demonstrated that the siRNA off-target effects were significantly reduced when
      the siRNAs were delivered into cells at the 3 nM concentration compared to 30 nM.
      Thus, the capability of our new design program to select highly potent siRNAs
      also renders increased RNAi specificity because these siRNAs can be used at a
      much lower concentration. The siRNA design web server is available at
      http://www5.appliedbiosystems.com/tools/siDesign/.

PMID- 19846597
TI  - Increased risk of thyroid pathology in patients with thyroid hemiagenesis:
      results of a large cohort case-control study.
AB  - OBJECTIVE: Thyroid hemiagenesis (THA) is an anomaly resulting from the
      developmental failure of one thyroid lobe. Etiopathogenesis, clinical
      significance, and management of patients in whom THA is diagnosed are still a
      matter of debate. The aim of the study is to provide the first systematic
      analysis of a large cohort of subjects with THA. DESIGN: Forty patients with THA
      are described in comparison to a control group of 80 subjects with fully
      developed thyroid gland. METHODS: Serum concentrations of thyrotropin (TSH), free
      thyroxine (FT(4)), free triiodothyronine (FT(3)), and thyroid autoantibodies were
      measured. In 37 patients, thyroid ultrasonography and Tc-99m thyroid scintiscan
      were performed, followed by fine-needle aspiration biopsy if indicated. The
      remaining archival three cases were diagnosed with the use of I-131 scintiscan
      under basal conditions and after TSH stimulation. RESULTS: Patients with THA,
      while usually clinically euthyroid, presented with significantly higher levels of
      TSH and FT(3) as well as with higher FT(3)/FT(4) concentration in comparison to
      the control group. Furthermore, a higher incidence of associated functional,
      morphological, and autoimmune thyroid disorders in patients with THA was observed
      when compared to subjects with bilobate thyroid (P<0.05). CONCLUSIONS: Our
      results revealed that individuals with THA are more likely to develop thyroid
      pathology. The observed high incidence of associated pathologies is presumably
      due to long-lasting TSH overstimulation. Therefore, THA diagnosis should be
      followed by systematic observation and adequate levothyroxine treatment in
      patients with elevated TSH level.

PMID- 19846598
TI  - Predicting meiotic pathways in human fetal oogenesis.
AB  - Gene function prediction has proven valuable in formulating testable hypotheses.
      It is particularly useful for exploring biological processes that are
      experimentally intractable, such as meiotic initiation and progression in the
      human fetal ovary. In this study, we developed the first functional gene network
      for the human fetal ovary, HFOnet, by probabilistically integrating multiple
      genomic features using a naive Bayesian model. We demonstrated that this network
      could accurately recapture known functional connections between genes, as well as
      predict new connections. Our findings suggest that known meiosis-specific genes
      (i.e., with functions only in meiotic processes in the germ cells) make either no
      or a few functional connections but are highly clustered with neighbor genes. In
      contrast, known nonspecific meiotic genes (i.e., with functions in both meiotic
      and nonmeiotic processes in the germ cells and somatic cells) exhibit numerous
      connections but low clustering coefficients, indicating their role as central
      modulators of diverse pathways, including those in meiosis. We also predicted
      novel genes that may be involved in meiotic initiation and DNA repair. This
      global functional network provides a much-needed framework for exploring gene
      functions and pathway components in early human female meiosis that are difficult
      to tackle by traditional in vivo mammalian genetics.

PMID- 19846599
TI  - Osmotic stress induces oxidative cell damage to rhesus macaque spermatozoa.
AB  - Cryopreservation introduces extreme temperature and osmolality changes that
      impart lethal and sublethal effects on spermatozoa survival. Additionally,
      evidence indicates that the osmotic stress induced by cryopreservation causes
      oxidative stress to spermatozoa as well. Our objective was to determine the
      effect of reactive oxygen species (ROS) on rhesus macaque (Macaca mulatta) sperm
      function and to determine whether osmotic stress elicits the production of ROS.
      In the first experiment, the xanthine-xanthine oxidase (X-XO) system was used to
      generate the ROS superoxide anion (O(2)(-.)) and hydrogen peroxide (H(2)O(2)) in
      the presence or absence of the ROS scavengers superoxide dismutase and catalase,
      respectively. In the second experiment, osmotic stress was introduced by
      incubation of spermatozoa in a series of anisosmotic media ranging from 100 to
      1000 mOsmol/kg in the presence or absence of the antioxidant alpha-tocopherol.
      Treatment with the X-XO system resulted in a significant increase in the
      generation of O(2)(-.) and H(2)O(2) that was detectable using flow cytometry. The
      ROS generated by the X-XO system was dose dependent, and as the concentration of
      ROS increased, motility decreased and lipid peroxidation increased while no
      affect was observed on viability. Incubation of spermatozoa in anisosmotic media
      also resulted in an increase in O(2)(-.) generation and lipid peroxidation that
      was significantly decreased in the presence of the powerful antioxidant alpha
      tocopherol. These results clearly indicate that osmotic stress causes oxidative
      stress in rhesus macaque spermatozoa, which strongly supports the hypothesis that
      cryopreservation-induced osmotic stress may lead to oxidative cell damage.

PMID- 19846600
TI  - Defining the window of germline genesis in vitro from murine embryonic stem
      cells.
AB  - Bone morphogenetic protein (BMP) signaling is critical for germline establishment
      during mouse embryogenesis. To exploit its importance for induction of germline
      precursors in vitro, mouse embryonic stem cells (mESCs) were cultured as embryoid
      body (EB) aggregates with combinations of BMP2, BMP4, and BMP8B for 3-10 days. At
      Day 10 of culture, well-delineated clusters of POU5F1-positive (POU5F1+) cells
      were visible in BMP4-treated and BMP2-treated EBs; these were rarely detected in
      untreated and BMP8B-treated cultures. Quantitative mRNA analysis revealed that a
      significant elevation of markers associated with primordial germ cell development
      had occurred in the presence of BMP4 by Day 10, including late germline markers
      such as Ddx4 (Mvh). Reasoning that germline specification was established by Day
      10, we surveyed earlier time points for altered levels of germline marker mRNAs.
      A peak of early markers, Prdm1 (Blimp1), Ifitm3 (Fragilis), and Dppa3 (Stella),
      was measured in Day 3 to Day 4 EBs grown in BMP4, followed by a decrease at Day
      5. In contrast, other markers, Pou5f1, Nanog, Dazl, and Ddx4, progressively
      increased from Day 3 to Day 5. Transforming growth factor beta superfamily
      signaling components Acvr1 (ALK2), Smad1, and Smad5 remained relatively constant.
      Isolated POU5F1+ cells from BMP4-treated Day 5 EBs contained significantly
      elevated germline markers compared with POU5F1-negative cells, with a transcript
      profile differing from mESCs, verifying their unique identity. These results
      demonstrate that signaling by BMP2 and BMP4, but not BMP8B, enhances germline
      marker expression within EBs and identify Day 3 to Day 5 in EB differentiation as
      a window for specification of germ cells in vitro.

PMID- 19846601
TI  - Induction of dual specificity phosphatase 1 (DUSP1) by gonadotropin-releasing
      hormone (GnRH) and the role for gonadotropin subunit gene expression in mouse
      pituitary gonadotroph L beta T2 cells.
AB  - We examined the expression of dual specificity phosphatase 1 (DUSP1) by
      gonadotropin-releasing hormone (GnRH) stimulation and investigated the role of
      DUSP1 on gonadotropin gene expression using LbetaT2 gonadotroph cell line. DUSP1
      expression was markedly increased 60 min after GnRH stimulation, and mitogen
      activated protein kinase 3/1 (MAPK3/1) activation was gradually decreased after
      60 min. GnRH-induced MAPK3/1 activation was completely inhibited by U0126, a MEK
      inhibitor, whereas GnRH-induced DUSP1 expression was partially inhibited by
      U0126. GnRH-induced DUSP1 induction was inhibited by triptolide, a diterpenoid
      triepoxide. In contrast, this compound potentiated MAPK3/1 activation. U0126
      prevented GnRH-stimulated gonadotropin subunit promoter activation dose
      dependently, and 10 muM of U0126 reduced the effects of GnRH on the Lhb and Fshb
      promoters to 79.15% and 55.66%, respectively. GnRH-stimulated activation of Lhb
      and Fshb promoters as well as serum response factor (Srf) promoters were almost
      completely inhibited by triptolide, suggesting that this component had a
      nonspecific effect to the cells. Dusp1 siRNA reduced the expression of DUSP1 and
      augmented MAPK3/1 phosphorylation, but it did not increase of gonadotropin
      promoters. By overexpression of DUSP1, both GnRH-stimulated Lhb and Fshb
      promoters were significantly reduced. We have previously shown that insulin-like
      growth factor 1 (IGF1) increases MAPK3/1 but does not activate gonadotropin
      subunit promoters. IGF1 failed to induce DUSP1 expression. In addition, under
      pulsatile GnRH stimulation, DUSP1 expression was observed following high
      frequency GnRH pulses but not following low-frequency pulses. Our study
      demonstrated that DUSP1, induced by GnRH, functions not only as an MAPK3/1
      inactivating phosphatase but also as an important mediator in gonadotropin
      subunit gene expression regulation.

PMID- 19846602
TI  - Isolation, characterization, and culture of human spermatogonia.
AB  - This study was designed to isolate, characterize, and culture human
      spermatogonia. Using immunohistochemistry on tubule sections, we localized GPR125
      to the plasma membrane of a subset of the spermatogonia. Immunohistochemistry
      also showed that MAGEA4 was expressed in all spermatogonia (A(dark), A(pale), and
      type B) and possibly preleptotene spermatocytes. Notably, KIT was expressed in
      late spermatocytes and round spermatids, but apparently not in human
      spermatogonia. UCHL1 was found in the cytoplasm of spermatogonia, whereas POU5F1
      was not detected in any of the human germ cells. GFRA1 and ITGA6 were localized
      to the plasma membrane of the spermatogonia. Next, we isolated GPR125-positive
      spermatogonia from adult human testes using a two-step enzymatic digestion
      followed by magnetic-activated cell sorting. The isolated GPR125-positive cells
      coexpressed GPR125, ITGA6, THY1, and GFRA1, and they could be cultured for short
      periods of time and exhibited a marked increase in cell numbers as shown by a
      proliferation assay. Immunocytochemistry of putative stem cell genes after 2 wk
      in culture revealed that the cells were maintained in an undifferentiated state.
      MAPK1/3 phosphorylation was increased after 2 wk of culture of the GPR125
      positive spermatogonia compared to the freshly isolated cells. Taken together,
      these results indicate that human spermatogonia share some but not all phenotypes
      with spermatogonial stem cells (SSCs) and progenitors from other species. GPR125
      positive spermatogonia are phenotypically putative human SSCs and retain an
      undifferentiated status in vitro. This study provides novel insights into the
      molecular characteristics, isolation, and culture of human SSCs and/or
      progenitors and suggests that the MAPK1/3 pathway is involved in their
      proliferation.

PMID- 19846603
TI  - Genetic variation in pentraxin (PTX) 3 gene associates with PTX3 production and
      fertility in women.
AB  - Pentraxin 3 (PTX3) plays an important role in innate immune responses and in
      female fertility, as discovered with studies in mice. However, the role of PTX3
      in human fertility is unknown. Here, we report on a population-based study from a
      rural area of Upper East Ghana (n = 4346). We studied the association between the
      number of children given birth by women during their lifetime and ex vivo,
      lipopolysaccharide (LPS)-induced PTX3 production (n = 362). In addition, we
      studied the association of genetic variation in the PTX3 gene with PTX3
      production (n = 617) and with female fertility (n = 1999). We found that ex vivo
      LPS-induced PTX3 production was associated with fertility (P = 0.040).
      Furthermore, we identified genetic variants in the PTX3 gene that influence PTX3
      production, and also fertility. The strongest associations were observed for the
      rs6788044 single-nucleotide polymorphism (SNP). We found that carriers of this
      SNP had higher PTX3 production capacity (P = 0.003) and higher fertility (P =
      0.043). The results reported here provide the first evidence, based on protein
      production and analysis of polymorphisms, that the long pentraxin PTX3 plays a
      role in female fertility in humans.

PMID- 19846608
TI  - High-resolution nucleosome mapping reveals transcription-dependent promoter
      packaging.
AB  - Genome-wide mapping of nucleosomes has revealed a great deal about the
      relationships between chromatin structure and control of gene expression, and has
      led to mechanistic hypotheses regarding the rules by which chromatin structure is
      established. High-throughput sequencing has recently become the technology of
      choice for chromatin mapping studies, yet analysis of these experiments is still
      in its infancy. Here, we introduce a pipeline for analyzing deep sequencing maps
      of chromatin structure and apply it to data from S. cerevisiae. We analyze a
      digestion series where nucleosomes are isolated from under- and overdigested
      chromatin. We find that certain classes of nucleosomes are unusually susceptible
      or resistant to overdigestion, with promoter nucleosomes easily digested and mid
      coding region nucleosomes being quite stable. We find evidence for highly
      sensitive nucleosomes located within "nucleosome-free regions," suggesting that
      these regions are not always completely naked but instead are likely associated
      with easily digested nucleosomes. Finally, since RNA polymerase is the dominant
      energy-consuming machine that operates on the chromatin template, we analyze
      changes in chromatin structure when RNA polymerase is inactivated via a
      temperature-sensitive mutation. We find evidence that RNA polymerase plays a role
      in nucleosome eviction at promoters and is also responsible for retrograde shifts
      in nucleosomes during transcription. Loss of RNA polymerase results in a
      relaxation of chromatin structure to more closely match in vitro nucleosome
      positioning preferences. Together, these results provide analytical tools and
      experimental guidance for nucleosome mapping experiments, and help disentangle
      the interlinked processes of transcription and chromatin packaging.

PMID- 19846610
TI  - Evidence that corticotropin-releasing hormone modulates myometrial contractility
      during human pregnancy.
AB  - As human pregnancy advances, CRH increases exponentially and is hypothesized to
      trigger the transition from myometrial quiescence to active contractions at
      labor. Paradoxically, CRH stimulates cAMP production, suggesting it should cause
      relaxation. To evaluate CRH as a mediator of quiescence, the effect of CRH on
      contractions in preterm and term myometria with concurrent progesterone (P4) was
      determined. In late gestation, we hypothesized that high concentrations of CRH
      down-regulate agonist-activated-cAMP relaxatory pathways and that increased
      phosphodiesterase (PDE) activity induces heterologous down-regulation of agonist
      activated-cAMP pathways. CRH caused dose-dependent relaxation of spontaneously
      contracting myometrial strips of 31 +/- 8% (mean +/- sem; n = 12) and 35 +/- 20%
      (n = 3) in term and preterm samples, respectively. CRH with P4 pretreatment
      caused a 40 +/- 13% (n = 4) reduction in contractility, whereas in matched
      samples, CRH alone exerted a 26 +/- 6% (n = 4) reduction, with a shift of CRH
      dose-response curves (P < 0.01, ANOVA). Pretreatment of strips with 10(-7) m CRH
      did not attenuate relaxation induced by subsequent CRH (n = 3) or salbutamol
      (beta(2)-agonist) treatment (n = 9). PDE inhibition by rolipram showed a 2.2- and
      1.5-fold increase in maximal relaxation induced by CRH and salbutamol,
      respectively, with a shift of both dose-response curves (P < 0.05 and P < 0.01,
      ANOVA). In conclusion, CRH at physiological concentrations acts synergistically
      with P4 contributing to myometrial quiescence. P4 withdrawal may reduce CRH
      mediated relaxation. Our functional model does not support homologous or
      heterologous down-regulation of agonist-stimulated-cAMP pathways by high CRH
      concentrations. PDE inhibition potentiates CRH and salbutamol-induced relaxation.
      Up-regulation of PDEs, through chronic cAMP elevation by CRH, could provide a
      mechanism for down-regulation of agonist-stimulated-cAMP pathways at term.

PMID- 19846609
TI  - ProPhylER: a curated online resource for protein function and structure based on
      evolutionary constraint analyses.
AB  - ProPhylER (Protein Phylogeny and Evolutionary Rates) is a next-generation curated
      proteome resource that uses comparative sequence analysis to predict constraint
      and mutation impact for eukaryotic proteins. Its purpose is to inform any
      research program for which protein function and structure are relevant, by the
      predictive power of evolutionary constraint analyses. ProPhylER currently has
      nearly 9000 clusters of related proteins, including more than 200,000 sequences.
      It serves data via two interfaces. The "ProPhylER Interface" displays predictive
      analyses in sequence space; the "CrystalPainter" maps evolutionary constraints
      onto solved protein structures. Here we summarize ProPhylER's data content and
      analysis pipeline, demonstrate the use of ProPhylER's interfaces, and evaluate
      ProPhylER's unique regional analysis of evolutionary constraint. The high
      accuracy of ProPhylER's regional analysis complements the high resolution of its
      single-site analysis to effectively guide and inform structure-function
      investigations and predict the impact of polymorphisms.

PMID- 19846611
TI  - The spontaneous Ala147Thr amino acid substitution within the translocator protein
      influences pregnenolone production in lymphomonocytes of healthy individuals.
AB  - The de novo production of steroids and neurosteroids begins in mitochondria by
      the conversion of cholesterol to pregnenolone through cytochrome P450 side-chain
      cleavage (CYP11A1) enzymatic activity. The C-terminal amino acid domain of the
      translocator protein (TSPO) has been demonstrated to bind cholesterol, thereby
      determining its mitochondrial translocation. The goal of the present study was to
      investigate the effect of the Ala147Thr single-nucleotide polymorphism localized
      in this TSPO region on pregnenolone production in healthy volunteers.
      Pregnenolone production was evaluated in a peripheral cell model, represented by
      circulating lymphomonocytes. First, CYP11A1 expression, both at mRNA and protein
      level, was demonstrated. Pregnenolone production varied among genotype groups.
      Comparison of pregnenolone mean values revealed that Thr147 homozygous or
      heterozygous individuals had significantly lower pregnenolone levels compared
      with Ala147 homozygous individuals. These findings suggested a dominant effect of
      the minor allelic variant Thr147 to produce this first metabolite of the
      steroidogenesis pathway. Interestingly, Ala147 homozygous individuals exhibited
      significant higher levels of circulating cholesterol-rich low-density
      lipoproteins with respect to heterozygous individuals. In conclusion, our results
      demonstrate that the Ala147Thr spontaneous amino acid substitution within TSPO is
      able to affect pregnenolone production; this should encourage further studies to
      investigate its potential role in polygenic dyslipidemias.

PMID- 19846612
TI  - Effects of maternal dexamethasone treatment in early pregnancy on pituitary
      adrenal axis in fetal sheep.
AB  - Fetal exposure to elevated levels of bioactive glucocorticoids early in
      gestation, as in suspected cases of congenital adrenal hyperplasia, may result in
      adverse neurological events. Fetal hypothalamic-pituitary-adrenal development and
      function may be involved. We investigated immediate and long-term effects of
      maternal dexamethasone (DEX) administration early in pregnancy on fetal growth
      and pituitary-adrenal activity in sheep. Pregnant ewes carrying singleton fetuses
      (total n = 119) were randomized to control (2 ml saline/ewe) or DEX-treated
      groups (im injections of 0.14 mg/kg ewe weight . 12 h) at 40-41 d gestation (dG).
      At 50, 100, 125, and 140 dG, fetal plasma and tissues were collected. DEX-exposed
      fetuses were lighter than controls at 100 dG (P < 0.05) but not at any other
      times. Fetal plasma ACTH levels and pituitary POMC and PC-1 mRNA levels were
      similar between groups. Fetal plasma cortisol levels were significantly reduced
      after DEX exposure in both male and female fetuses at 50 dG (P < 0.05), were
      similar at 100 and 125 dG, but were significantly higher than controls at 140 dG.
      At 140 dG, there was increased adrenal P450C(17) and 3beta-HSD mRNA in female
      fetuses and reduced expression of ACTH-R mRNA in males. Fetal hepatic CBG mRNA
      levels mimicked plasma cortisol patterns. DEX exposure reduced CBG only in males
      at 50 dG (P < 0.05). Placental mRNA levels of 11beta-HSD2 were increased after
      DEX in males (P < 0.05). Therefore, in sheep, early DEX may alter the
      developmental trajectory of the fetal hypothalamic-pituitary-adrenal axis,
      directly increasing fetal adrenal activation but not anterior pituitary function.
      In females, this effect may be attributed, in part, to increased fetal adrenal
      steroidogenic activity.

PMID- 19846613
TI  - Does finger fat produce sex differences in second to fourth digit ratios?

PMID- 19846615
TI  - Influence of saccade efference copy on the spatiotemporal properties of
      remapping: a neural network study.
AB  - Remapping of gaze-centered target-position signals across saccades has been
      observed in the superior colliculus and several cortical areas. It is generally
      assumed that this remapping is driven by saccade-related signals. What is not
      known is how the different potential forms of this signal (i.e., visual,
      visuomotor, or motor) might influence this remapping. We trained a three-layer
      recurrent neural network to update target position (represented as a "hill" of
      activity in a gaze-centered topographic map) across saccades, using discrete time
      steps and backpropagation-through-time algorithm. Updating was driven by an
      efference copy of one of three saccade-related signals: a transient visual
      response to the saccade-target in two-dimensional (2-D) topographic coordinates
      (Vtop), a temporally extended motor burst in 2-D topographic coordinates (Mtop),
      or a 3-D eye velocity signal in brain stem coordinates (EV). The Vtop model
      produced presaccadic remapping in the output layer, with a "jumping hill" of
      activity and intrasaccadic suppression. The Mtop model also produced presaccadic
      remapping with a dispersed moving hill of activity that closely reproduced the
      quantitative results of Sommer and Wurtz. The EV model produced a coherent moving
      hill of activity but failed to produce presaccadic remapping. When eye velocity
      and a topographic (Vtop or Mtop) updater signal were used together, the remapping
      relied primarily on the topographic signal. An analysis of the hidden layer
      activity revealed that the transient remapping was highly dispersed across hidden
      layer units in both Vtop and Mtop models but tightly clustered in the EV model.
      These results show that the nature of the updater signal influences both the
      mechanism and final dynamics of remapping. Taken together with the currently
      known physiology, our simulations suggest that different brain areas might rely
      on different signals and mechanisms for updating that should be further
      distinguishable through currently available single- and multiunit recording
      paradigms.

PMID- 19846616
TI  - A prolongation of the postspike afterhyperpolarization following spike trains can
      partly explain the lower firing rates at derecruitment than those at recruitment.
AB  - The original motivation for this study was the observation in previous human
      experiments that the motor neuron firing frequency (recorded from the motor units
      in the EMG) was lower at derecruitment than that at recruitment, with slow
      linearly varying voluntary contractions. Are the lower firing rates at
      derecruitment correlated with a change in the postspike afterhyperpolarization
      (AHP) after preceding spike trains? This question was investigated by
      intracellular recordings from cat motor neurons in both unanesthetized and
      anesthetized preparations. The firing frequencies at recruitment and
      derecruitment were compared during slow triangular current injections mimicking
      the slow linearly varying voluntary contractions in humans. There was a lower
      frequency at derecruitment in almost all motor neurons (83 of 86 motor neurons;
      mean = 3.35 Hz). Thus intrinsic mechanisms play an important role for the lower
      frequencies at derecruitment. This was independent of whether the current
      injection had activated persistent inward current (PIC; plateau potentials,
      secondary range firing). It was found that a preceding spike train could prolong
      the AHP duration following a subsequent spike. The lower rate at derecruitment
      matches the prolongation of the AHP. However, a quantitative comparison between
      the lowest firing frequency and AHP duration for individual motor neurons reveal
      that the predicted lowest firing frequency does not match the absolute AHP
      duration; the lowest frequency is lower than that predicted from AHP duration in
      fast motoneurons and higher than expected in slow motoneurons. It is suggested
      that these deviations are explained by the presence of synaptic noise as well as
      recruitment of PICs below firing threshold. Thus synaptic noise may allow spike
      discharge even after the end of the AHP in "fast" motor neurons, whereas synaptic
      noise and PICs below spike threshold tend to give higher minimum firing
      frequencies in "slow" motor neurons than predicted from AHP duration.

PMID- 19846617
TI  - Sensory reweighting in targeted reaching: effects of conscious effort, error
      history, and target salience.
AB  - When both visual and proprioceptive information are available about the position
      of a part of the body, the brain weights and combines these sources to form a
      single estimate, often modeled by minimum variance integration. These weights are
      known to vary with different circumstances, but the type of information causing
      the brain to change weights (reweight) is unknown. Here we studied reweighting in
      the context of estimating the position of a hand for the purpose of reaching it
      with the other hand. Subjects reached to visual (V), proprioceptive (P), or
      combined (VP) targets in a virtual reality setup. We calculated weights for
      vision and proprioception by comparing endpoints on VP reaches with endpoints on
      P and V reaches. Endpoint visual feedback was manipulated to control completely
      for the error history seen by subjects. In different experiments, we manipulated
      target salience, conscious effort, or statistics of the visual error history to
      see if these cues could cause reweighting. Most subjects could reweight strongly
      by conscious effort. Changes in target salience reliably caused reweighting, but
      seen error history alone did not. We also found that experimental weights can be
      predicted by minimizing the variance of visual and proprioceptive estimates,
      supporting the idea that minimum variance integration is an important principle
      of sensorimotor processing.

PMID- 19846618
TI  - Motor outputs in a multitasking network: relative contributions of inputs and
      experience-dependent network states.
AB  - Network outputs elicited by a specific stimulus may differ radically depending on
      the momentary network state. One class of networks states-experience-dependent
      states-is known to operate in numerous networks, yet the fundamental question
      concerning the relative role that inputs and states play in determining the
      network outputs remains to be investigated in a behaviorally relevant manner.
      Because previous work indicated that in the isolated nervous system the motor
      outputs of the Aplysia feeding network are affected by experience-dependent
      states, we sought to establish the behavioral relevance of these outputs. We
      analyzed the phasing of firing of radula opening motoneurons (B44 and B48)
      relative to other previously characterized motoneurons. We found that the overall
      pattern of motoneuronal firing corresponds to the phasing of movements during
      feeding behavior, thus indicating a behavioral relevance of network outputs.
      Previous studies suggested that network inputs act to trigger a response rather
      than to shape its characteristics, with the latter function being fulfilled by
      network states. We show this is an oversimplification. In a rested state,
      different inputs elicited distinct responses, indicating that inputs not only
      trigger but also shape the responses. However, depending on the combination of
      inputs and states, responses were either dramatically altered by the network
      state or were indistinguishable from those observed in the rested state. We
      suggest that the relative contributions of inputs and states are dynamically
      regulated and, rather than being fixed, depend on the specifics of states and
      inputs.

PMID- 19846619
TI  - Slow spike frequency adaptation in neurons of the rat subthalamic nucleus.
AB  - Neurons of the subthalamic nucleus (STN) are very sensitive to applied currents,
      firing at 10-20/s during spontaneous activity, but increasing to peak firing
      rates of 200/s with applied currents <0.5 nA. They receive a powerful tonic
      excitatory input from neurons in the cerebral cortex, yet in vivo maintain an
      irregular firing rate only slightly higher than the autonomous firing rate seen
      in slices. Spike frequency adaptation acts to normalize background firing rate by
      removing slow trends in firing due to changes in average input. Subthalamic
      neurons have been previously described as showing little spike frequency
      adaptation, but this was based on tests using brief stimuli. We applied long
      duration depolarizing current steps to STN neurons in slices and observed a very
      strong spike frequency adaptation with a time constant of 20 s and that recovered
      at a similar rate. This adaptation could return firing to near-baseline levels
      during prolonged current pulses that transiently drove the cells at high rates.
      The current responsible for adaptation was studied in voltage clamp during and
      after high-frequency driving of the cell and was determined to be a slowly
      accumulating K(+) current. This current was independent of calcium or sodium
      entry and could be induced with long-duration voltage steps after blockade of
      action potentials. In addition to the adaptation current, driven firing produced
      slow inactivation of the persistent Na(+) current, which also contributed to the
      reduced excitability of STN cells during and after driven firing.

PMID- 19846620
TI  - A color-based visualization technique for multielectrode spike trains.
AB  - Multi electrode recordings of neuronal activity provide an overwhelming amount of
      data that is often difficult to analyze and interpret. Although various methods
      exist for treating multielectrode datasets quantitatively, there is a
      particularly prominent lack of techniques that enable a quick visual exploration
      of such datasets. Here, by using Kohonen self-organizing maps, we propose a
      simple technique that allows for the representation of multiple spike trains
      through a sequence of color-coded population activity vectors. When multiple
      color sequences are grouped according to a certain criterion, e.g., by
      stimulation condition or recording time, one can inspect an entire dataset
      visually and extract quickly information about the identity, stimulus-locking and
      temporal distribution of multi-neuron activity patterns. Color sequences can be
      computed on various time scales revealing different aspects of the temporal
      dynamics and can emphasize high-order correlation patterns that are not
      detectable with pairwise techniques. Furthermore, this technique is useful for
      determining the stability of neuronal responses during a recording session. Due
      to its simplicity and reliance on perceptual grouping, the method is useful for
      both quick on-line visualization of incoming data and for more detailed post hoc
      analyses.

PMID- 19846621
TI  - Functional coupling between motor and sensory nerves through contraction of
      sphincters in the pudendal area of the female cat.
AB  - The question of whether skin receptors might help in the perception of muscle
      contraction and body movement has not been settled. The present study gives
      direct evidence of skin receptor firing in close coincidence with the contraction
      of the vaginal and anal sphincters. The distal stump of the sectioned motor
      pudendal nerve was stimulated. Single shocks induced a wavelike increase in the
      lumen pressure of the distal vagina and the anal canal, as well as constriction
      of the vaginal introitus and the anus. The constriction pulls on and moves the
      surrounding skin, which was initially detected visually. In the present
      experiments, a thin strain gauge that pressed on the skin surface detected its
      displacement. Single shocks to the motor nerve induced a wave of skin movement
      with maximal amplitude at 5 mm from the anus and propagated with decrement beyond
      35 mm. The peripheral terminals of the sensory pudendal nerve and the posterior
      femoral nerve supply the skin that moves. Sensory axons from both nerves fired in
      response to both tactile stimulation and the skin movement produced by the
      constriction of the orifices (motor-sensory coupling). In cats with all nerves
      intact, a single shock to the sensory nerves induced reflex waves of skin
      movement and lumen pressure (sensory-motor coupling). Both couplings provide
      evidence for a feedforward action that might help to maintain the female posture
      during mating and to the perception of muscle contraction.

PMID- 19846622
TI  - Altered GABAA,slow inhibition and network oscillations in mice lacking the GABAA
      receptor beta3 subunit.
AB  - Phasic GABAergic inhibition in hippocampus and neocortex falls into two
      kinetically distinct categories, GABA(A,fast) and GABA(A,slow). In hippocampal
      area CA1, GABA(A,fast) is generally believed to underlie gamma oscillations,
      whereas the contribution of GABA(A,slow) to hippocampal rhythms has been
      speculative. Hypothesizing that GABA(A) receptors containing the beta(3) subunit
      contribute to GABA(A,slow) inhibition and that slow inhibitory synapses control
      excitability as well as contribute to network rhythms, we investigated the
      consequences of this subunit's absence on synaptic inhibition and network
      function. In pyramidal neurons of GABA(A) receptor beta(3) subunit-deficient
      (beta(3)(-/-)) mice, spontaneous GABA(A,slow) inhibitory postsynaptic currents
      (IPSCs) were much less frequent, and evoked GABA(A,slow) currents were much
      smaller than in wild-type mice. Fittingly, long-lasting recurrent inhibition of
      population spikes was less powerful in the mutant, indicating that receptors
      containing beta(3) subunits contribute substantially to GABA(A,slow) currents in
      pyramidal neurons. By contrast, slow inhibitory control of GABA(A,fast)-producing
      interneurons was unaffected in beta(3)(-/-) mice. In vivo hippocampal network
      activity was markedly different in the two genotypes. In beta(3)(-/-) mice,
      epileptiform activity was observed, and theta oscillations were weaker, slower,
      less regular and less well coordinated across laminae compared with wild-type
      mice, whereas gamma oscillations were weaker and faster. The amplitude modulation
      of gamma oscillations at theta frequency ("nesting") was preserved but was less
      well coordinated with theta oscillations. With the caveat that seizure-induced
      changes in inhibitory circuits might have contributed to the changes observed in
      the mutant animals, our results point to a strong contribution of beta(3)
      subunits to slow GABAergic inhibition onto pyramidal neurons but not onto
      GABA(A,fast) -producing interneurons and support different roles for these slow
      inhibitory synapses in the generation and coordination of hippocampal network
      rhythms.

PMID- 19846623
TI  - Slow excitation of cultured rat retinal ganglion cells by activating group I
      metabotropic glutamate receptors.
AB  - As in many CNS neurons, retinal ganglion cells (RGCs) receive fast synaptic
      activation through postsynaptic ionotropic receptors. However, the potential role
      of postsynaptic group I metabotropic glutamate receptors (mGluRs) in these
      neurons is unknown. In this study we first demonstrated that the selective group
      I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) increased intracellular
      calcium concentration in neurons within the ganglion cell layer of the rat
      retina. This prompted us to use an immunopanned-RGC and cortical astroglia
      coculture preparation to explore the effect of group I mGluR activation on the
      electrophysiological properties of cultured RGCs. Using perforated patch-clamp
      recordings in current-clamp configuration, we found that application of DHPG
      increased spontaneous spiking and depolarized the resting membrane potential of
      RGCs. This boosting effect was attributed to an increase in membrane resistance
      due to blockade of a background K(+) conductance. Further experiments showed that
      the group I mGluR-sensitive K(+) conductance was not blocked by 3 mM Cs(+), but
      was sensitive to acidification. Pharmacological studies indicated that the effect
      of DHPG on RGCs was mediated by the mGluR1 rather than the mGluR5 receptor
      subtype. Our results suggest a facilitatory role for group I mGluR activation in
      modulating RGC excitability in the mammalian inner retina.

PMID- 19846624
TI  - Enhancement of ITD coding within the initial stages of the auditory pathway.
AB  - Sensory systems use a variety of strategies to increase the signal-to-noise ratio
      in their inputs at the receptor level. However, important cues for sound
      localization are not present at the individual ears but are computed after inputs
      from the two ears converge within the brain, and we hypothesized that additional
      strategies to enhance the representation of these cues might be employed in the
      initial stages after binaural convergence. Specifically, we investigated the
      transformation that takes place between the first two stages of the gerbil
      auditory pathway that are sensitive to differences in the arrival time of a sound
      at the two ears (interaural time differences; ITDs): the medial superior olive
      (MSO), where ITD tuning originates, and the dorsal nucleus of the lateral
      lemniscus (DNLL), to which the MSO sends direct projections. We use a combined
      experimental and computational approach to demonstrate that the coding of ITDs is
      dramatically enhanced between these two stages, with the mutual information in
      the responses of single neurons increasing by a factor of 2. We also show that
      this enhancement is related to an increase in dynamic range for neurons with high
      preferred frequencies and a decrease in variability for neurons with low
      preferred frequencies. These results suggest that a major role of the initial
      stages of the ITD pathway may be to enhance the representation created at the
      site of coincidence detection and illustrate the potential of this pathway as a
      model system for the study of strategies for enhancing sensory representations in
      the mammalian brain.

PMID- 19846625
TI  - The subthalamic nucleus in primary dystonia: single-unit discharge
      characteristics.
AB  - Most models of dystonia pathophysiology predict alterations of activity in the
      basal ganglia thalamocortical motor circuit. The globus pallidus interna (GPi)
      shows bursting and oscillatory neuronal discharge in both human dystonia and in
      animal models, but it is not clear which intrinsic basal ganglia pathways are
      implicated in this abnormal output. The subthalamic nucleus (STN) receives
      prominent excitatory input directly from cortical areas implicated in dystonia
      pathogenesis and inhibitory input from the external globus pallidus. The goal of
      this study was to elucidate the role of the STN in dystonia by analyzing STN
      neuronal discharge in patients with idiopathic dystonia. Data were collected in
      awake patients undergoing microelectrode recording for implantation of STN deep
      brain stimulation electrodes. We recorded 62 STN neurons in 9 patients with
      primary dystonia. As a comparison group, we recorded 143 STN neurons in 20
      patients with Parkinson's disease (PD). Single-unit activity was discriminated
      off-line by principal component analysis and evaluated with respect to discharge
      rate, bursting, and oscillatory activity. The mean STN discharge rate in dystonia
      patients was 26.3 Hz (SD 13.6), which was lower than that in the PD patients
      (35.6 Hz, SD 15.2), but higher than published values for subjects without basal
      ganglia dysfunction. Oscillatory activity was found in both disorders, with a
      higher proportion of units oscillating in the beta range in PD. Bursting
      discharge was a prominent feature of both dystonia and PD, whereas sensory
      receptive fields were expanded in PD compared with dystonia. The STN firing
      characteristics, in conjunction with those previously published for GPi, suggest
      that bursting and oscillatory discharge in basal ganglia output may be
      transmitted via pathways involving the STN and provide a pathophysiologic
      rationale for STN as a surgical target in dystonia.

PMID- 19846626
TI  - Perception of auditory, visual, and egocentric spatial alignment adapts
      differently to changes in eye position.
AB  - Vision and audition represent the outside world in spatial synergy that is
      crucial for guiding natural activities. Input conveying eye-in-head position is
      needed to maintain spatial congruence because the eyes move in the head while the
      ears remain head-fixed. Recently, we reported that the human perception of
      auditory space shifts with changes in eye position. In this study, we examined
      whether this phenomenon is 1) dependent on a visual fixation reference, 2)
      selective for frequency bands (high-pass and low-pass noise) related to specific
      auditory spatial channels, 3) matched by a shift in the perceived straight-ahead
      (PSA), and 4) accompanied by a spatial shift for visual and/or bimodal (visual
      and auditory) targets. Subjects were tested in a dark echo-attenuated chamber
      with their heads fixed facing a cylindrical screen, behind which a mobile
      speaker/LED presented targets across the frontal field. Subjects fixated
      alternating reference spots (0, +/-20 degrees ) horizontally or vertically while
      either localizing targets or indicating PSA using a laser pointer. Results showed
      that the spatial shift induced by ocular eccentricity is 1) preserved for
      auditory targets without a visual fixation reference, 2) generalized for all
      frequency bands, and thus all auditory spatial channels, 3) paralleled by a shift
      in PSA, and 4) restricted to auditory space. Findings are consistent with a set
      point control strategy by which eye position governs multimodal spatial
      alignment. The phenomenon is robust for auditory space and egocentric perception,
      and highlights the importance of controlling for eye position in the examination
      of spatial perception and behavior.

PMID- 19846627
TI  - Evaluation of automated and manual commercial DNA extraction methods for recovery
      of Brucella DNA from suspensions and spiked swabs.
AB  - This study evaluated automated and manual commercial DNA extraction methods for
      their ability to recover DNA from Brucella species in phosphate-buffered saline
      (PBS) suspension and from spiked swab specimens. Six extraction methods,
      representing several of the methodologies which are commercially available for
      DNA extraction, as well as representing various throughput capacities, were
      evaluated: the MagNA Pure Compact and the MagNA Pure LC instruments, the IT 1-2-3
      DNA sample purification kit, the MasterPure Complete DNA and RNA purification
      kit, the QIAamp DNA blood mini kit, and the UltraClean microbial DNA isolation
      kit. These six extraction methods were performed upon three pathogenic Brucella
      species: B. abortus, B. melitensis, and B. suis. Viability testing of the DNA
      extracts indicated that all six extraction methods were efficient at inactivating
      virulent Brucella spp. Real-time PCR analysis using Brucella genus- and species
      specific TaqMan assays revealed that use of the MasterPure kit resulted in
      superior levels of detection from bacterial suspensions, while the MasterPure kit
      and MagNA Pure Compact performed equally well for extraction of spiked swab
      samples. This study demonstrated that DNA extraction methodologies differ in
      their ability to recover Brucella DNA from PBS bacterial suspensions and from
      swab specimens and, thus, that the extraction method used for a given type of
      sample matrix can influence the sensitivity of real-time PCR assays for Brucella.

PMID- 19846628
TI  - Delineation of a new species of the Borrelia burgdorferi Sensu Lato Complex,
      Borrelia americana sp. nov.
AB  - Analysis of borrelia isolates collected from ticks, birds, and rodents from the
      southeastern United States revealed the presence of well-established populations
      of Borrelia burgdorferi sensu stricto, Borrelia bissettii, Borrelia carolinensis,
      and Borrelia sp. nov. Multilocus sequence analysis of five genomic loci from
      seven samples representing Borrelia sp. nov. isolated from nymphal Ixodes minor
      collected in South Carolina showed their close relatedness to California strains
      known as genomospecies 1 and separation from any other known species of the B.
      burgdorferi sensu lato complex. One nucleotide difference in the size of the 5S
      23S intergenic spacer region, one substitution in 16S rRNA gene signature
      nucleotides, and silent nucleotide substitutions in sequences of the gene
      encoding flagellin and the gene p66 clearly separate Borrelia sp. nov. isolates
      from South Carolina into two subgroups. The sequences of isolates of each
      subgroup share the same restriction fragment length polymorphism patterns of the
      5S-23S intergenic spacer region and contain unique signature nucleotides in the
      16S rRNA gene. We propose that seven Borrelia sp. nov. isolates from South
      Carolina and two California isolates designated as genomospecies 1 comprise a
      single species, which we name Borrelia americana sp. nov. The currently
      recognized geographic distribution of B. americana is South Carolina and
      California. All strains are associated with Ixodes pacificus or Ixodes minor and
      their rodent and bird hosts.

PMID- 19846629
TI  - Incubation alone is adequate as a culturing technique for cardiac rhythm
      management devices.
AB  - There exist no standardized methods for culturing cardiac rhythm management
      devices. To identify the most optimal culturing method, we compared various
      techniques that comprise vortex, sonication, and incubation or combinations
      thereof. Incubation alone yielded bacterial colony counts similar to those of
      other culturing combinations and is the least labor-intensive.

PMID- 19846630
TI  - Diverse characteristics of the CagA gene of Helicobacter pylori strains collected
      from patients from southern vietnam with gastric cancer and peptic ulcer.
AB  - The pathogenesis of gastroduodenal diseases is related to the diversity of
      Helicobacter pylori strains. CagA-positive strains are more likely to cause
      gastric cancer than CagA-negative strains. Based on EPIYA (Glu-Pro-Ile-Tyr-Ala)
      motifs at the carboxyl terminus corresponding to phosphorylation sites, H. pylori
      CagA is divided into East Asian CagA and Western CagA. The former type prevails
      in East Asia and is more closely associated with gastric cancer. The present
      study used full sequences of the cagA gene and CagA protein of 22 H. pylori
      strains in gastric cancer and peptic ulcer patients from Southern Vietnam to make
      a comparison of genetic homology among Vietnamese strains and between them and
      other strains in East Asia. A phylogenetic tree was constructed based on full
      amino acid sequences of 22 Vietnamese strains in accordance with 54 references
      from around the world. The cagA gene was found in all Vietnamese H. pylori
      strains. Twenty-one of 22 (95.5%) strains belonged to the East Asian type and had
      similar characteristics of amino acid sequence at the carboxyl terminus to other
      strains from the East Asian region. From evidence of East Asian CagA and
      epidemiologic cancerous lesions in Vietnam, H. pylori-infected Vietnamese can be
      classified into a high-risk group for gastric cancer, but further studies on the
      interaction among environmental and virulence factors should be done. Finally,
      phylogenetic data support that there is a Japanese subtype in the Western CagA
      type.

PMID- 19846631
TI  - Improved performance of a rapid office-based stool test for detection of
      Helicobacter pylori in children before and after therapy.
AB  - A modified version of a rapid office based one-step monoclonal immunoassay for
      detection of Helicobacter pylori antigen in stool samples from children was
      evaluated against biopsy specimen-based methods and compared to a monoclonal
      enzyme immunoassay using the same antigen. Blinded stool samples from 185
      children (0.3 to 18.2 years) were investigated at the time of upper endoscopy
      prior to anti-H. pylori therapy; 62 children were H. pylori infected and 123
      noninfected according to predefined reference standards. Samples obtained 6 to 8
      weeks after anti-H. pylori therapy were available from 58 children (3.8 to 17.7
      years) and were compared to results of the [(13)C]urea breath test (14/58 were
      positive). The rapid stool tests were performed by two independent readers. Of
      243 rapid tests performed, 1 (0.4%) was invalid for technical reasons. Equivocal
      results (very weak line) were reported 16 times by reader 1 and 27 times by
      reader 2. When equivocal results were considered positive, the two observers
      agreed on 76 positive and 160 negative results and disagreed on 7 samples (2.9%).
      The sensitivity was 90.8% for reader 1 and 85.5% for reader 2, and the
      specificity was 91.0% and 93.4%, respectively. The monoclonal enzyme immunoassay
      revealed a sensitivity and specificity of 94.7% and 97.6%, respectively. The
      modified chromatographic immunoassay is a good alternative in settings or
      situations when the monoclonal enzyme immunoassay or the [(13)C]urea breath test
      are not available or feasible. In order to improve sensitivity, very weak lines
      should be considered positive test results.

PMID- 19846632
TI  - Outbreak of acute respiratory disease caused by Mycoplasma pneumoniae on board a
      deployed U.S. navy ship.
AB  - We identified 179 cases of acute respiratory illness including 50 cases of
      radiographically confirmed pneumonia over the course of 4 months on a deployed
      U.S. Navy vessel. Laboratory tests showed Mycoplasma pneumoniae to be the
      etiological agent. This report represents the first published description of a
      shipboard outbreak of this pathogen.

PMID- 19846633
TI  - Multicenter comparative evaluation of five commercial methods for toxoplasma DNA
      extraction from amniotic fluid.
AB  - Over the past few years, a number of new nucleic acid extraction methods and
      extraction platforms using chemistry combined with magnetic or silica particles
      have been developed, in combination with instruments to facilitate the extraction
      procedure. The objective of the present study was to investigate the suitability
      of these automated methods for the isolation of Toxoplasma gondii DNA from
      amniotic fluid (AF). Therefore, three automated procedures were compared to two
      commercialized manual extraction methods. The MagNA Pure Compact (Roche),
      BioRobot EZ1 (Qiagen), and easyMAG (bioMerieux) automated procedures were
      compared to two manual DNA extraction kits, the QIAamp DNA minikit (Qiagen) and
      the High Pure PCR template preparation kit (Roche). Evaluation was carried out
      with two specific Toxoplasma PCRs (targeting the 529-bp repeat element),
      inhibitor search PCRs, and human beta-globin PCRs. The samples each consisted of
      4 ml of AF with or without a calibrated Toxoplasma gondii RH strain suspension
      (0, 1, 2.5, 5, and 25 tachyzoites/ml). All PCR assays were laboratory-developed
      real-time PCR assays, using either TaqMan or fluorescent resonance energy
      transfer probes. A total of 1,178 PCRs were performed, including 978 Toxoplasma
      PCRs. The automated and manual methods were similar in sensitivity for DNA
      extraction from T. gondii at the highest concentration (25 Toxoplasma gondii
      cells/ml). However, our results showed that the DNA extraction procedures led to
      variable efficacy in isolating low concentrations of tachyzoites in AF samples
      (<5 Toxoplasma gondii cells/ml), a difference that might have repercussions since
      low parasite concentrations in AF exist and can lead to congenital toxoplasmosis.

PMID- 19846634
TI  - Multiplex PCR to diagnose bloodstream infections in patients admitted from the
      emergency department with sepsis.
AB  - Sepsis is caused by a heterogeneous group of infectious etiologies. Early
      diagnosis and the provision of appropriate antimicrobial therapy correlate with
      positive clinical outcomes. Current microbiological techniques are limited in
      their diagnostic capacities and timeliness. Multiplex PCR has the potential to
      rapidly identify bloodstream infections and fill this diagnostic gap. We
      identified patients from two large academic hospital emergency departments with
      suspected sepsis. The results of a multiplex PCR that could detect 25 bacterial
      and fungal pathogens were compared to those of blood culture. The results were
      analyzed with respect to the likelihood of infection, sepsis severity, the site
      of infection, and the effect of prior antibiotic therapy. We enrolled 306
      subjects with suspected sepsis. Of these, 43 were later determined not to have
      infectious etiologies. Of the remaining 263 subjects, 70% had sepsis, 16% had
      severe sepsis, and 14% had septic shock. The majority had a definite infection
      (41.5%) or a probable infection (30.7%). Blood culture and PCR performed
      similarly with samples from patients with clinically defined infections (areas
      under the receiver operating characteristic curves, 0.64 and 0.60, respectively).
      However, blood culture identified more cases of septicemia than PCR among
      patients with an identified infectious etiology (66 and 46, respectively; P =
      0.0004). The two tests performed similarly when the results were stratified by
      sepsis severity or infection site. Blood culture tended to detect infections more
      frequently among patients who had previously received antibiotics (P = 0.06).
      Conversely, PCR identified an additional 24 organisms that blood culture failed
      to detect. Real-time multiplex PCR has the potential to serve as an adjunct to
      conventional blood culture, adding diagnostic yield and shortening the time to
      pathogen identification.

PMID- 19846635
TI  - Comparison of PCR and culture for screening of vancomycin-resistant Enterococci:
      highly disparate results for vanA and vanB.
AB  - We compared PCR to conventional culture for the detection of vancomycin-resistant
      enterococci (VRE) in 30,835 rectal samples over a 3-year period. The positive and
      negative predictive values of vanB PCR were 1.42% and 99.9%, respectively. A
      positive vanB result by PCR is poorly predictive and necessitates culture for
      differentiation of VRE-positive and -negative individuals.

PMID- 19846636
TI  - Polymorphic exact tandem repeat A (PETRA): a newly defined lineage of
      mycobacterium tuberculosis in israel originating predominantly in Sub-Saharan
      Africa.
AB  - As part of the Israel National Program for Prevention and Control of
      Tuberculosis, the molecular epidemiology of new tuberculosis cases is monitored.
      Prospective screening showed that about 20% of all new cases of culture-positive
      tuberculosis (43 of 222) in Israel in the year 2008 were caused by certain
      Mycobacterium tuberculosis strains of the central Asian (CAS) spoligotype
      lineage. The identity and similarity of these strains by mycobacterial
      interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing
      form a lineage we call PETRA for polymorphic at locus ETR A. The name PETRA was
      given to 79 strains we have found since the year 2000, because the largest number
      of strains with MIRU-VNTR profiles identical other than at locus A formed three
      groups, including 5 of 10 strains that had deleted the ETR A region from their
      genomes. No PETRA strain was found to be multiple drug resistant (resistant to
      both isoniazid and rifampin [rifampicin]). Most patients (75% [58 of 77 patients
      of known origin]) infected with PETRA were of sub-Saharan African origins. The
      genotypes associated with the 79 PETRA lineage strains presented in this paper
      suggest that the PETRA lineage is a large, major contributor to new tuberculosis
      cases in Israel.

PMID- 19846637
TI  - Evaluation of a new commercial TaqMan PCR assay for direct detection of the
      clostridium difficile toxin B gene in clinical stool specimens.
AB  - The ProGastro Cd assay (Prodesse, Inc., Waukesha, WI) is a new commercial TaqMan
      PCR assay that detects tcdB. The ProGastro Cd assay was compared to the Wampole
      Clostridium difficile toxin B test (TOX-B test; TechLab, Blacksburg, VA), a cell
      culture cytotoxicity neutralization assay (CCCNA), and to anaerobic toxigenic
      bacterial culture, as the "gold standard," for 285 clinical stool specimens.
      Assays were independently performed according to manufacturers' directions. A 1.0
      ml sample was removed from the stool specimen, of which 20 microl was used for
      extraction on the NucliSENS easyMAG platform (bioMerieux, Inc., Durham, NC) for
      the Prodesse ProGastro Cd assay and 200 microl of the stool filtrate was used for
      the TOX-B CCCNA. Anaerobic toxigenic culture was done by heating an additional
      1.0 ml of the stool sample to 80 degrees C for 10 min before inoculation onto
      modified cycloserine, cefoxitin, and fructose agar with horse blood (Remel,
      Lenexa, KS) and into a prereduced chopped meat glucose broth (BBL, BD
      Diagnostics, Sparks, MD). The prevalence of toxin-producing strains of C.
      difficile was 15.7% (n = 44) as determined by anaerobic toxigenic culture. The
      sensitivity, specificity, and positive and negative predictive values of the
      Prodesse ProGastro Cd assay compared to the TOX-B test were 83.3%, 95.6%, 69.4%,
      and 98%, respectively. Compared to toxigenic culture, the sensitivity,
      specificity, and positive and negative predictive values of the Prodesse
      ProGastro Cd assay were 77.3%, 99.2%, 94.4%, and 95.9%, respectively, and those
      of the TOX-B test were 63.6%, 99.2%, 93.3%, and 93.6%, respectively. Although no
      statistical difference (Fisher's exact test) was detected (P = 0.242) between the
      sensitivities of the Prodesse ProGastro Cd assay and a standard CCCNA compared to
      anaerobic culture for the detection of toxigenic C. difficile, the Prodesse
      ProGastro Cd assay did detect more toxigenic C. difficile isolates than the
      CCCNA.

PMID- 19846638
TI  - Subtyping of emm1 group A Streptococci causing invasive infections in France.
AB  - By combining PCR amplification of toxin-encoding genes and sic gene sequencing,
      we distinguished 24 genotypes among 47 M/emm1 group A streptococci isolated from
      children and adults in France in 9 cases of infection comprising four clusters
      and 38 unrelated invasive infection cases used as controls.

PMID- 19846639
TI  - Changes in multidrug resistance of enteric bacteria following an intervention to
      reduce antimicrobial resistance in dairy calves.
AB  - An intervention study was conducted to determine whether discontinuing the
      feeding of milk replacer medicated with oxytetracycline and neomycin to preweaned
      calves reduced antimicrobial resistance in Salmonella, Campylobacter, and
      Escherichia coli bacteria. Results demonstrated that the intervention did reduce
      multidrug resistance in these bacteria but that other factors also influenced
      multidrug resistance.

PMID- 19846641
TI  - Serum (1-3)-beta-D-glucan as a tool for diagnosis of Pneumocystis jirovecii
      pneumonia in patients with human immunodeficiency virus infection or
      hematological malignancy.
AB  - (1-3)-Beta-D-Glucan (BG) reactivity was tested in serum samples from 28 patients
      with human immunodeficiency virus infection or a hematological malignancy and
      Pneumocystis jirovecii pneumonia (PCP) and 28 control patients. The sensitivity
      and specificity of BG detection with the Fungitell assay for PCP were 100 and
      96.4%, respectively, using a cutoff value of 100 pg/ml. Serum BG testing looks
      promising for the noninvasive diagnosis of PCP. Our data suggest that a higher
      cutoff value for the diagnosis of PCP than for the diagnosis of invasive
      aspergillosis or candidiasis could be used safely and will improve the
      specificity of the test.

PMID- 19846640
TI  - Negative correlation of distributions of Streptococcus cristatus and
      Porphyromonas gingivalis in subgingival plaque.
AB  - Porphyromonas gingivalis is one of the major causative agents of adult
      periodontitis. One of the features of this periodontal pathogen is its ability to
      attach to a variety of oral bacterial surfaces and to colonize subgingival dental
      plaque. We have shown that Streptococcus cristatus CC5A inhibits expression of
      fimA, a gene encoding the major protein subunit of long fimbriae in P.
      gingivalis; as a result, S. cristatus interrupts formation of P. gingivalis
      biofilms. Here we further demonstrate that the inhibitory activity of S.
      cristatus affects multiple strains of P. gingivalis and that optimal inhibitory
      activity correlates with levels of arginine deiminase expression in S. cristatus.
      More strikingly, the impact of S. cristatus on P. gingivalis colonization was
      revealed by comparing levels of P. gingivalis and S. cristatus in subgingival
      dental plaque. Spearman correlation analysis indicated a negative correlation
      between the distributions of S. cristatus and P. gingivalis (r = -0.57; P <
      0.05). These data suggest that some early colonizers of dental plaque, such as S.
      cristatus, may be beneficial to the host by antagonizing the colonization and
      accumulation of periodontal pathogens such as P. gingivalis.

PMID- 19846642
TI  - Pyrosequencing for rapid detection of Mycobacterium tuberculosis resistance to
      rifampin, isoniazid, and fluoroquinolones.
AB  - After isoniazid and rifampin (rifampicin), the next pivotal drug class in
      Mycobacterium tuberculosis treatment is the fluoroquinolone class. Mutations in
      resistance-determining regions (RDR) of the rpoB, katG, and gyrA genes occur with
      frequencies of 97%, 50%, and 85% among M. tuberculosis isolates resistant to
      rifampin, isoniazid, and fluoroquinolones, respectively. Sequences are highly
      conserved, and certain mutations correlate well with phenotypic resistance. We
      developed a pyrosequencing assay to determine M. tuberculosis genotypic
      resistance to rifampin, isoniazid, and fluoroquinolones. We characterized 102 M.
      tuberculosis clinical isolates from the Philippines for susceptibility to
      rifampin, isoniazid, and ofloxacin by using the conventional submerged-disk
      proportion method and validated our pyrosequencing assay using these isolates.
      DNA was extracted and amplified by using PCR primers directed toward the RDR of
      the rpoB, katG, and gyrA genes, and pyrosequencing was performed on the extracts.
      The M. tuberculosis H37Rv strain (ATCC 25618) was used as the reference strain.
      The sensitivities and specificities of pyrosequencing were 96.7% and 97.3%, 63.8%
      and 100%, and 70.0% and 100% for the detection of resistance to rifampin,
      isoniazid, and ofloxacin, respectively. Pyrosequencing is thus a rapid and
      accurate method for detecting M. tuberculosis resistance to these three drugs.

PMID- 19846644
TI  - Development and evaluation of one-step TaqMan real-time reverse transcription-PCR
      assays targeting nucleoprotein, matrix, and hemagglutinin genes of equine
      influenza virus.
AB  - The objective of this study was to develop and evaluate new TaqMan real-time
      reverse transcription-PCR (rRT-PCR) assays by the use of the minor groove binding
      probe to detect a wide range of equine influenza virus (EIV) strains comprising
      both subtypes of the virus (H3N8 and H7N7). A total of eight rRT-PCR assays were
      developed, targeting the nucleoprotein (NP), matrix (M), and hemagglutinin (HA)
      genes of the two EIV subtypes. None of the eight assays cross-reacted with any of
      the other known equine respiratory viruses. Three rRT-PCR assays (EqFlu NP, M,
      and HA3) which can detect strains of the H3N8 subtype were evaluated using nasal
      swabs received for routine diagnosis and swabs collected from experimentally
      inoculated horses. All three rRT-PCR assays have greater specificity and
      sensitivity than virus isolation by egg inoculation (93%, 89%, and 87%
      sensitivity for EqFlu NP, EqFlu M, and EqFlu HA3 assays, respectively). These
      assays had analytical sensitivities of >or=10 EIV RNA molecules. Comparison of
      the sensitivities of rRT-PCR assays targeting the NP and M genes of both subtypes
      with egg inoculation and the Directigen Flu A test clearly shows that molecular
      assays provide the highest sensitivity. The EqFlu HA7 assay targeting the H7 HA
      gene is highly specific for the H7N7 subtype of EIV. It should enable highly
      reliable surveillance for the H7N7 subtype, which is thought to be extinct or
      possibly still circulating at a very low level in nature. The assays that we
      developed provide a fast and reliable means of EIV diagnosis and subtype
      identification of EIV subtypes.

PMID- 19846643
TI  - Multicenter study of prevalence of nontuberculous mycobacteria in patients with
      cystic fibrosis in france.
AB  - We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM)
      involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with
      cystic fibrosis in France. The overall NTM prevalence (percentage of patients
      with at least one positive culture) was 6.6% (104/1,582 patients), with
      prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater
      Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and
      Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM,
      and the only ones associated with fulfillment of the American Thoracic Society
      bacteriological criteria for NTM lung disease. The "new" species, Mycobacterium
      bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates.
      MABSC species were isolated at all ages, with a prevalence peak between 11 and 15
      years of age (5.8%), while MAC species reached their highest prevalence value
      among patients over 25 years of age (2.2%).

PMID- 19846645
TI  - (CGG)4-based PCR as a novel tool for discrimination of uropathogenic Escherichia
      coli strains: comparison with enterobacterial repetitive intergenic consensus
      PCR.
AB  - Urinary tract infections are one of the most frequent bacterial diseases in
      humans, and Escherichia coli is most often the relevant pathogen. A specific
      pathotype of E. coli, known as uropathogenic E. coli (UPEC), often causes serious
      and difficult-to-treat infections of the urinary tract. We propose a new single
      tube screening tool that uses an (N)(6)(CGG)(4) primer to generate fingerprint
      profiles that allow rapid discrimination and epidemiology of this group of
      bacteria. We found 71 different CGG-PCR profiles among 127 E. coli strains, while
      enterobacterial repetitive intergenic consensus (ERIC)-PCR of the same group
      yielded only 28 profiles. Additionally, the (CGG)(4)-based PCR test turned out to
      be very effective for clustering UPEC strains exhibiting multiple virulence genes
      and usually belonging to the B2 phylogenetic group, and it separated these
      strains from E. coli strains lacking most of the UPEC-specific virulence factors.
      Since the reproducibility of the CGG-PCR screen is higher than that of ERIC-PCR,
      our test should be a valuable means of increasing the discriminatory power of
      current UPEC typing schemes.

PMID- 19846646
TI  - Evaluation of adult chronic Chagas' heart disease diagnosis by molecular and
      serological methods.
AB  - Chagas' disease caused by Trypanosoma cruzi is endemic in Latin America. T. cruzi
      presents heterogeneous populations and comprises two main genetic lineages, named
      T. cruzi I and T. cruzi II. Diagnosis in the chronic phase is based on
      conventional serological tests, including indirect immunofluorescence (IIF) and
      enzyme-linked immunosorbent assay (ELISA), and diagnosis in the acute phase based
      on parasitological methods, including hemoculture. The objective of this study
      was to evaluate the diagnostic procedures of Chagas' disease in adult patients in
      the chronic phase by using a PCR assay and conventional serological tests,
      including TESA-blot as the gold standard. Samples were obtained from 240 clinical
      chronic chagasic patients. The sensitivities, compared to that of TESA-blot, were
      70% for PCR using the kinetoplast region, 75% for PCR using the nuclear
      repetitive region, 99% for IIF, and 95% for ELISA. According to the serological
      tests results, we recommend that researchers assess the reliability and
      sensitivity of the commercial kit Chagatest ELISA recombinant, version 3.0
      (Chagatest Rec v3.0; Wiener Lab, Rosario, Argentina), due to the lack of
      sensitivity. Based on our analysis, we concluded that PCR cannot be validated as
      a conventional diagnostic technique for Chagas' disease. These data have been
      corroborated by low levels of concordance with serology test results. It is
      recommended that PCR be used only for alternative diagnostic support. Using the
      nuclear repetitive region of T. cruzi, PCR could also be applicable for
      monitoring patients receiving etiologic treatment.

PMID- 19846647
TI  - CD64 index provides simple and predictive testing for detection and monitoring of
      sepsis and bacterial infection in hospital patients.
AB  - The rapid diagnosis and management of bacterial infection are heavily dependent
      upon clinical assessment. Blood culture may take up to 2 days for results and may
      be suspect. Surface neutrophil CD64 expression has been shown to be upregulated
      in cases of bacterial infection. Recently, a standardized kit for the CD64 index
      was used in neonatal intensive care units, showing high sensitivity and
      specificity for bacterial infections. Our study was designed to confirm and
      extend these results to adult hospital patients and to determine the impact of
      this testing on a clinical laboratory's finances and staffing. CD64 indices were
      performed with peripheral blood drawn in tandem with blood cultures from 109
      patients over a 2-month period. We found that a CD64 index of <or=1.19 was
      predictive of "no growth" blood culture results. An index of >1.19 was predictive
      of an ultimate clinical and/or culture diagnosis of infection with a sensitivity
      and specificity of 94.6% and 88.7%, respectively. Positive and negative
      predictive values were 89.8% and 94%, respectively. The CD64 index was easily
      performed using our flow cytometer and staff, producing minimal alteration in
      clinical workflow. A 7-day-a-week testing schedule will result in some additional
      expense but will be more than offset by the expected cost savings. The CD64 index
      is a useful and inexpensive test for improving the diagnosis and management of
      hospital patients with bacterial infection. It can be readily performed by
      clinical laboratories and could result in considerable savings for the
      institution.

PMID- 19846649
TI  - Microbiological characteristics of community-associated Staphylococcus aureus
      causing uncomplicated bacteremia and infective endocarditis.
AB  - Staphylococcus aureus is an important cause of community-associated bacteremia
      (SAB) and infective endocarditis (IE). No significant differences in distribution
      or frequency of genes encoding virulence factors, including genes encoding
      adhesins, were found between isolates from the IE and SAB groups (12 IE and 10
      SAB patients).

PMID- 19846648
TI  - Clinical application of real-time PCR to screening critically ill and emergency
      care surgical patients for methicillin-resistant Staphylococcus aureus: a
      quantitative analytical study.
AB  - The clinical utility of real-time PCR screening assays for methicillin
      (methicillin)-resistant Staphylococcus aureus (MRSA) colonization is constrained
      by the predictive values of their results: as MRSA prevalence falls, the assay's
      positive predictive value (PPV) drops, and a rising proportion of positive PCR
      assays will not be confirmed by culture. We provide a quantitative analysis of
      universal PCR screening of critical care and emergency surgical patients using
      the BD GeneOhm MRSA PCR system, involving 3,294 assays over six months. A total
      of 248 PCR assays (7.7%) were positive; however, 88 failed to be confirmed by
      culture, giving a PPV of 65%. Multivariate analysis was performed to compare PCR
      positive culture-positive (P+C+) and PCR-positive culture-negative (P+C-) assays.
      P+C- results were positively associated with a history of methicillin-sensitive
      Staphylococcus aureus infection or colonization (odds ratio [OR], 3.15; 95%
      confidence interval [CI], 1.32 to 7.54) and high PCR thresholds of signal
      intensity, indicative of a low concentration of target DNA (OR, 1.19 per cycle;
      95% CI, 1.11 to 1.26). P+C- results were negatively associated with a history of
      MRSA infection or colonization (OR, 0.19; 95% CI, 0.09 to 0.42) and male sex (OR,
      0.40; 95% CI, 0.20 to 0.81). P+C+ patients were significantly more likely to have
      subsequent positive MRSA culture assays and microbiological evidence of clinical
      MRSA infection. The risk of subsequent MRSA infection in P+C- patients was not
      significantly different from that in case-matched PCR-negative controls. We
      conclude that, given the low PPV and poor correlation between a PCR-positive
      assay and the clinical outcome, it would be prudent to await culture confirmation
      before altering infection control measures on the basis of a positive PCR result.

PMID- 19846650
TI  - Multicenter comparison of two norovirus ORF2-based genotyping protocols.
AB  - Point source norovirus outbreaks can be difficult to track due to high background
      levels of the virus in the environment and the limited strain variation in some
      genotyping regions. However, rapid and accurate source identification can limit
      the spread of a foodborne outbreak and reduce the number of cases. Harmonization
      of genotyping assays is critical for enabling the rapid exchange of sequence data
      nationally and internationally. Several regions of the genome have been proposed
      for this purpose, but no consensus has been reached. In the present study, two
      standardized genotyping protocols (region C and region D) were evaluated by nine
      laboratories in Canada and the United States, using a coded panel of 96 fecal
      specimens representing 22 different norovirus genotypes. Overall, region C typing
      had a success rate of 78% compared to 52% for region D; however, region D
      provides greater nucleotide sequence diversity for identifying new GII.4 variant
      strains. Significant differences in the genotyping success rate were observed
      among the nine participating laboratories (10% to 100%) and among the different
      genotypes (6% to 100%). For several genogroup II strains, reduced region D
      amplification correlated directly with mismatches between primer sequences and
      the template. Based on overall performance, we recommend the region C protocol
      for routine genotyping of noroviruses, while the region D protocol may be useful
      for identifying new GII.4 variants. Standardized genotyping protocols will enable
      rapid exchange of outbreak and sequence data through electronic norovirus
      surveillance networks.

PMID- 19846651
TI  - Rhizomucor variabilis var. regularior and Hormographiella aspergillata infections
      in a leukemic bone marrow transplant recipient with refractory neutropenia.
AB  - Rhizomucor variabilis and Hormographiella aspergillata rarely cause human
      infections. This report details a fatal case of a 14-year-old female with
      leukemia posthematopoietic cell transplant and relapse with refractory
      pancytopenia. The patient first developed an R. variabilis var. regularior palate
      infection and later developed a cutaneous H. aspergillata infection while on
      posaconazole and caspofungin therapy.

PMID- 19846652
TI  - Improved selective isolation of Bordetella pertussis by use of modified
      cyclodextrin solid medium.
AB  - We have developed a modified cyclodextrin solid (MCS) medium using the selective
      antibiotic cefdinir. MCS medium exhibited higher sensitivity (95.6%; any culture
      positive sample as reference) and greater inhibition of nasopharyngeal flora than
      did Bordet-Gengou agar (65.2%, P = 0.009) or cyclodextrin solid medium (39.1%, P
      < 0.001).

PMID- 19846653
TI  - Presence of genes encoding the panton-valentine leukocidin exotoxin is not the
      primary determinant of outcome in patients with complicated skin and skin
      structure infections due to methicillin-resistant Staphylococcus aureus: results
      of a multinational trial.
AB  - The role of Panton-Valentine leukocidin (PVL) in determining the severity and
      outcome of complicated skin and skin structure infections (cSSSI) caused by
      methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) is controversial.
      We evaluated potential associations between clinical outcome and PVL status by
      using MRSA isolates from patients enrolled in two large, multinational phase
      three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS
      program). MRSA isolates from microbiologically evaluable patients were genotyped
      by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative
      virulence determinants. A single baseline pathogen of MRSA was isolated from 522
      microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of
      these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1%
      (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely
      than those with pvl-negative MRSA to be young, to be North American, and to
      present with major abscesses (P < 0.001 for each). Patients were significantly
      more likely to be cured if they were infected with pvl-positive MRSA than if they
      were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This
      observation remained statistically significant after adjustment for presence of
      abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study
      medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec
      type IV, and agr group II genes were also associated with clinical response (P <
      0.05). This contemporary, international study demonstrates that pvl was not the
      primary determinant of outcome in patients with MRSA cSSSI.

PMID- 19846654
TI  - Prevalence and genotypes of Helicobacter pylori in gastric biopsy specimens from
      patients with gastroduodenal pathologies in the Cukurova Region of Turkey.
AB  - The effects of Helicobacter pylori genotypes on clinical prognosis in the
      Cukurova region of Turkey were investigated by PCR. The prevalence of type I
      strains carrying the s1c allele, unlike in neighboring regions and countries, was
      found to be significantly higher in patients with gastritis and/or gastric ulcers
      (P = 0.001), and that of type I strains carrying the s1a allele was found to be
      significantly higher in patients with duodenal ulcers (P < 0.001). The cagA gene
      was strongly associated with the more virulent vacA genotypes (P < 0.001).

PMID- 19846655
TI  - Determination of Echinocandin MICs for Candida species in less than 8 hours:
      comparison of the rapid susceptibility assay with the Clinical and Laboratory
      Standards Institute's broth microdilution assay.
AB  - The echinocandins prevent fungal cell wall synthesis by inhibiting beta-1,3
      glucan synthesis, a significant glucose-consuming process. Previous studies
      suggested that echinocandin inhibitory activity is evident within 1 h of
      exposure. We hypothesized that a susceptibility assay based on glucose
      consumption may provide clinically useful MICs rapidly. The rapid susceptibility
      assay (RSA), which provides MICs in less than 8 h, was compared with the standard
      broth microdilution susceptibility assay (Clinical and Laboratory Standards
      Institute, document M27-A3, 2008) for 56 Candida species strains. Variables which
      are known to influence MICs determined by the M27-A3 method were also assessed
      for their effects on the RSA results. Excellent agreement (>90%) between the
      results of the RSA and M27-A3 methods was achieved for all three FDA-approved
      echinocandins (micafungin, caspofungin, and anidulafungin). Candida lusitaniae
      strains were responsible for most of the discordant results. Assay variables such
      as the test medium, the age of the inoculum culture, and the presence of human
      serum affected MIC results from the RSA and the M27-A3 method similarly. The RSA
      is equivalent to the standard M27-A3 method for determining echinocandin MICs for
      Candida species. The RSA provides MIC results in less than 8 h and can be applied
      to old and young yeast colonies. The assay could potentially provide clinically
      useful MICs on the same day that yeast growth from a specimen is first detected
      on solid medium.

PMID- 19846656
TI  - Heteroresistance to teicoplanin in Enterococcus faecium harboring the vanA gene.

PMID- 19846657
TI  - Small Cajal body-specific RNAs of Drosophila function in the absence of Cajal
      bodies.
AB  - During their biogenesis small nuclear RNAs (snRNAs) undergo multiple covalent
      modifications that require guide RNAs to direct methylase and pseudouridylase
      enzymes to the appropriate nucleotides. Because of their localization in the
      nuclear Cajal body (CB), these guide RNAs are known as small CB-specific RNAs
      (scaRNAs). Using a fluorescent primer extension technique, we mapped the modified
      nucleotides in Drosophila U1, U2, U4, and U5 snRNAs. By fluorescent in situ
      hybridization (FISH) we showed that seven Drosophila scaRNAs are concentrated in
      easily detectable CBs. We used two assays based on Xenopus oocyte nuclei to
      demonstrate that three of these Drosophila scaRNAs do, in fact, function as guide
      RNAs. In flies null for the CB marker protein coilin, CBs are absent and there
      are no localized FISH signals for the scaRNAs. Nevertheless, biochemical
      experiments show that scaRNAs are present at normal levels and snRNAs are
      properly modified. Our experiments demonstrate that several scaRNAs are
      concentrated as expected in the CBs of wild-type Drosophila, but they function
      equally well in the nucleoplasm of mutant flies that lack CBs. We propose that
      the snRNA modification machinery is not limited to CBs, but is dispersed
      throughout the nucleoplasm of cells in general.

PMID- 19846658
TI  - Bub3p facilitates spindle checkpoint silencing in fission yeast.
AB  - Although critical for spindle checkpoint signaling, the role kinetochores play in
      anaphase promoting complex (APC) inhibition remains unclear. Here we show that
      spindle checkpoint proteins are severely depleted from unattached kinetochores in
      fission yeast cells lacking Bub3p. Surprisingly, a robust mitotic arrest is
      maintained in the majority of bub3 Delta cells, yet they die, suggesting that
      Bub3p is essential for successful checkpoint recovery. During recovery, two
      defects are observed: (1) cells mis-segregate chromosomes and (2) anaphase onset
      is significantly delayed. We show that Bub3p is required to activate the APC upon
      inhibition of Aurora kinase activity in checkpoint-arrested cells, suggesting
      that Bub3p is required for efficient checkpoint silencing downstream of Aurora
      kinase. Together, these results suggest that spindle checkpoint signals can be
      amplified in the nucleoplasm, yet kinetochore localization of spindle checkpoint
      components is required for proper recovery from a spindle checkpoint-dependent
      arrest.

PMID- 19846659
TI  - Synthetic lethal genetic interactions that decrease somatic cell proliferation in
      Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer
      drug target.
AB  - Somatic mutations causing chromosome instability (CIN) in tumors can be exploited
      for selective killing of cancer cells by knockdown of second-site genes causing
      synthetic lethality. We tested and statistically validated synthetic lethal (SL)
      interactions between mutations in six Saccharomyces cerevisiae CIN genes
      orthologous to genes mutated in colon tumors and five additional CIN genes. To
      identify which SL interactions are conserved in higher organisms and represent
      potential chemotherapeutic targets, we developed an assay system in
      Caenorhabditis elegans to test genetic interactions causing synthetic
      proliferation defects in somatic cells. We made use of postembryonic RNA
      interference and the vulval cell lineage of C. elegans as a readout for somatic
      cell proliferation defects. We identified SL interactions between members of the
      cohesin complex and CTF4, RAD27, and components of the alternative RFC(CTF18)
      complex. The genetic interactions tested are highly conserved between S.
      cerevisiae and C. elegans and suggest that the alternative RFC components DCC1,
      CTF8, and CTF18 are ideal therapeutic targets because of their mild phenotype
      when knocked down singly in C. elegans. Furthermore, the C. elegans assay system
      will contribute to our knowledge of genetic interactions in a multicellular
      animal and is a powerful approach to identify new cancer therapeutic targets.

PMID- 19846660
TI  - Binding the atypical RA domain of Ste50p to the unfolded Opy2p cytoplasmic tail
      is essential for the high-osmolarity glycerol pathway.
AB  - Activation of the high-osmolarity glycerol (HOG) pathway for osmoregulation in
      the yeast Saccharomyces cerevisiae involves interaction of the adaptor Ste50p
      with the cytoplasmic tail of single-transmembrane protein Opy2p. We have
      determined the solution structure of the Ste50p-RA (Ras association) domain, and
      it shows an atypical RA fold lacking the beta1 and beta2 strands of the canonical
      motif. Although the core of the RA domain is fully functional in the pheromone
      response, an additional region is required for the HOG pathway activation. Two
      peptide motifs within the intrinsically disordered cytoplasmic tail of Opy2p
      defined by NMR spectroscopy physically interact with the Step50p-RA domain. These
      Opy2p-derived peptides bind overlapping regions of the Step50p-RA domain with
      similarly weak affinities, suggesting a multivalent interaction of these proteins
      as a crucial point of control of the HOG pathway. As well, overall selection of
      signaling pathways depends on functionally distinct regions of the Ste50p-RA
      domain, implicating this element in the control of global regulatory decisions.

PMID- 19846661
TI  - Bone morphogenetic protein-6 promotes cerebellar granule neurons survival by
      activation of the MEK/ERK/CREB pathway.
AB  - Bone morphogenetic proteins (BMPs) have been implicated in the generation and
      postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined
      the eventual role of BMPs on the survival of these neurons. Lack of
      depolarization causes CGC death by apoptosis in vivo, a phenomenon that is
      mimicked in vitro by deprivation of high potassium in cultured CGCs. We have
      found that BMP-6, but not BMP-7, is able to block low potassium-mediated
      apoptosis in CGCs. The neuroprotective effect of BMP-6 is not accompanied by an
      increase of Smad translocation to the nucleus, suggesting that the canonical
      pathway is not involved. By contrast, activation of the MEK/ERK/CREB pathway by
      BMP-6 is necessary for its neuroprotective effect, which involves inhibition of
      caspase activity and an increase in Bcl-2 protein levels. Other pathways involved
      in the regulation of CGC survival, such as the c-Jun terminal kinase and the
      phosphatidylinositol 3-kinase (PI3K)-Akt/PKB, were not affected by BMP-6.
      Moreover, failure of BMP-7 to activate the MEK/ERK/CREB pathway could explain its
      inability to protect CGCs from low potassium-mediated apoptosis. Thus, this study
      demonstrates that BMP-6 acting through the noncanonical MEK/ERK/CREB pathway
      plays a crucial role on CGC survival.

PMID- 19846662
TI  - MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2.
AB  - The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c
      myc expression and involved in control of tumorigenesis. Gastric cancer is one of
      the most frequent neoplasms and lethal malignancies worldwide. So far, the
      regulatory mechanism of its aggressiveness has not been clearly characterized.
      Here we studied roles of MBP-1 in gastric cancer progression. We found that cell
      proliferation was inhibited by MBP-1 overexpression in human stomach
      adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities
      of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1
      knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was
      suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by
      MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed
      epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on
      cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1
      suppressed tumor progression in SC-M1 cells were through inhibition of COX-2
      expression. MBP-1 also exerted a suppressive effect on tumor progression of other
      gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results
      suggest that MBP-1-suppressed COX-2 expression plays an important role in the
      inhibition of growth and progression of gastric cancer.

PMID- 19846663
TI  - Exploring the roles of diaphanous and enabled activity in shaping the balance
      between filopodia and lamellipodia.
AB  - During migration cell protrusions power cell extension and sample the
      environment. Different cells produce different protrusions, from keratocytes
      dominated by lamellipodia, to growth cones combining filopodia and lamellipodia,
      to dendritic spines. One key challenge is to determine how the toolkit of actin
      regulators are coordinated to generate these diverse protrusive arrays. Here we
      use Drosophila leading-edge (LE) cells to explore how Diaphanous (Dia)-related
      formins and Ena/VASP proteins cooperate in this process. We first dissect the Dia
      regulatory region, revealing novel roles for the GTPase-binding and FH3 domains
      in cortical localization, filopodial initiation, and lengthening. Second, we
      provide evidence that activating Dia mobilizes Ena from storage places near the
      LE to act at the LE. Further, Dia and Ena coIP and can recruit one another to new
      locations, suggesting cooperation is key to their mechanisms of action. Third, we
      directly explore the functional relationship between Dia and Ena, varying their
      levels and activity separately in the same cell type. Surprisingly, although each
      is sufficient to induce filopodia, together they induce lamellipodia. Our data
      suggest they work together in a complex and nonadditive way, with the ratio
      between active Dia and Ena being one factor that modulates the balance between
      filopodia and lamellipodia.

PMID- 19846664
TI  - Neuronal IP3 3-kinase is an F-actin-bundling protein: role in dendritic targeting
      and regulation of spine morphology.
AB  - The actin microstructure in dendritic spines is involved in synaptic plasticity.
      Inositol trisphosphate 3-kinase A (ITPKA) terminates Ins(1,4,5)P(3) signals
      emanating from spines and also binds filamentous actin (F-actin) through its
      amino terminal region (amino acids 1-66, N66). Here we investigated how ITPKA,
      independent of its kinase activity, regulates dendritic spine F-actin
      microstructure. We show that the N66 region of the protein mediates F-actin
      bundling. An N66 fusion protein bundled F-actin in vitro, and the bundling
      involved N66 dimerization. By mutagenesis we identified a point mutation in a
      predicted helical region that eliminated both F-actin binding and bundling,
      rendering the enzyme cytosolic. A fusion protein containing a minimal helical
      region (amino acids 9-52, N9-52) bound F-actin in vitro and in cells, but had
      lower affinity. In hippocampal neurons, GFP-tagged N66 expression was highly
      polarized, with targeting of the enzyme predominantly to spines. By contrast, N9
      52-GFP expression occurred in actin-rich structures in dendrites and growth
      cones. Expression of N66-GFP tripled the length of dendritic protrusions, induced
      longer dendritic spine necks, and induced polarized actin motility in time-lapse
      assays. These results suggest that, in addition to its ability to regulate
      intracellular Ca(2+) via Ins(1,4,5)P(3) metabolism, ITPKA regulates structural
      plasticity.

PMID- 19846665
TI  - Notch signaling and developmental cell-cycle arrest in Drosophila polar follicle
      cells.
AB  - Temporal and spatial regulation of cell division is critical for proper
      development of multicellular organisms. An important aspect of this regulation is
      cell-cycle arrest, which in many cell types is coupled with differentiated
      status. Here we report that the polar cells--a group of follicle cells
      differentiated early during Drosophila oogenesis--are arrested at G2 phase and
      can serve as a model cell type for investigation of developmental regulation of
      cell-cycle arrest. On examining the effects of String, a mitosis-promoting
      phosphatase Cdc25 homolog, and Notch signaling in polar cells, we found that
      misexpression of String can trigger mitosis in existing polar cells to induce
      extra polar cells. Normally, differentiation of the polar cells requires Notch
      signaling. We found that the Notch-induced extra polar cells arise through
      recruitment of the neighboring cells rather than promotion of proliferation, and
      they are also arrested at G2 phase. Notch signaling is probably involved in down
      regulating String in polar cells, thus inducing the G2 cell-cycle arrest.

PMID- 19846668
TI  - Calcium and phosphate compatibility in low-osmolarity parenteral nutrition
      admixtures intended for peripheral vein administration.
AB  - BACKGROUND: Precipitation of calcium (Ca) and phosphate (P) salts can lead to
      potentially lethal outcomes, especially in low-osmolarity parenteral nutrition
      (LO-PN) formulations. Three concentrations of amino acids (AA) and 2
      concentrations of calcium gluconate and sodium phosphate injections on the
      compatibility of Ca and P in LO-PN admixtures were studied. METHODS: Final AA
      concentrations of 1%, 2%, or 3% (n = 3) and 5% glucose (G) were prepared with
      either 2.5 or 5 mmol/L (5 or 10 mEq) of Ca (n = 2) and 15 or 30 mmol/L of P (n =
      2) for a total of 12 base (3 x 2 x 2) formulations. Triplicate bags of each were
      analyzed for subvisible micro-precipitates using the light obscuration (or
      extinction) method for particle counts per milliliter (PC) in the size range of
      1.8-50 mum at 7 time intervals over 48 hours stored at 30 degrees C +/- 0.2
      degrees C. Visual evaluation was performed using a high-intensity lamp against a
      black background for detection of macro-precipitates. The pH of all 36 admixtures
      was measured at 0 and 48 hours. Any precipitated material was isolated and
      characterized by polarized light microscopy and infrared spectroscopy. RESULTS:
      Of the 12 base LO-PN formulations tested, those containing 1% and 2% AA with 5
      mmol/L of Ca and 30 mmol/L of P showed significant increases in PC, and some
      resulted in visible dibasic calcium phosphate precipitation. Analyses of variance
      based on concentrations of AA, Ca, P, and time were highly significant
      independent variables for increases in the PC of potentially embolic particles,
      that is, sizes >5 mum (P < .0001). The lowest concentrations of Ca and P, 2.5 and
      15 mmol/L, respectively, had significantly lower PC (P < .05) for all sizes
      compared with the other Ca and P combinations. CONCLUSIONS: LO-PN admixtures (AA
      </= 3%; G = 5%) should not contain more than 2.5 mmol/L of Ca from calcium
      gluconate injection and no more than 15 mmol/L of P from potassium or sodium
      phosphates injection.

PMID- 19846667
TI  - Distinct roles for CARMIL isoforms in cell migration.
AB  - Molecular mechanisms for cell migration, especially how signaling and
      cytoskeletal systems are integrated, are not understood well. Here, we examined
      the role of CARMIL (capping protein, Arp2/3, and Myosin-I linker) family proteins
      in migrating cells. Vertebrates express three conserved genes for CARMIL, and we
      examined the functions of the two CARMIL genes expressed in migrating human
      cultured cells. Both isoforms, CARMIL1 and 2, were necessary for cell migration,
      but for different reasons. CARMIL1 localized to lamellipodia and macropinosomes,
      and loss of its function caused loss of lamellipodial actin, along with defects
      in protrusion, ruffling, and macropinocytosis. CARMIL1-knockdown cells showed
      loss of activation of Rac1, and CARMIL1 was biochemically associated with the GEF
      Trio. CARMIL2, in contrast, colocalized with vimentin intermediate filaments, and
      loss of its function caused a distinctive multipolar phenotype. Loss of CARMIL2
      also caused decreased levels of myosin-IIB, which may contribute to the polarity
      phenotype. Expression of one CARMIL isoform was not able to rescue the knockdown
      phenotypes of the other. Thus, the two isoforms are both important for cell
      migration, but they have distinct functions.

PMID- 19846669
TI  - Identification of a dominant endoplasmic reticulum-retention signal in yellow
      fever virus pre-membrane protein.
AB  - Yellow fever virus (YFV) encodes two envelope proteins, pre-membrane (prM) and
      envelope (E), that accumulate in the endoplasmic reticulum (ER). The C termini of
      prM and E form two antiparallel transmembrane alpha-helices that contain ER
      retention signals. To understand further the ER retention of the prME
      heterodimer, we characterized the subcellular localization of chimeric proteins
      made of a reporter protein fused to the transmembrane segments of YFV envelope
      proteins. We showed that at least three of the transmembrane segments of the prME
      heterodimer are ER-retention signals. Interestingly, increasing the length of
      these alpha-helices led to the export of the chimeric proteins out of the ER.
      Furthermore, adding a diacidic export signal at the C terminus of the first
      transmembrane segment of the E protein also induced export to the cell surface.
      However, adding this export signal at the C terminus of the first transmembrane
      segment of E in the context of prME did not change the subcellular localization
      of the prME heterodimer, suggesting the presence of a stronger ER-retention
      signal outside the first transmembrane segment of E. Importantly, the diacidic
      export motif added to the C terminus of the first transmembrane segment of the
      prM protein was not sufficient to export a chimeric protein out of the ER,
      indicating that this sequence is a dominant ER-retention signal. Together, these
      data indicate that a combination of several signals of different strengths
      contributes to the ER retention of the YFV envelope protein heterodimer.

PMID- 19846666
TI  - Mitochondrial reactive oxygen species mediate GPCR-induced TACE/ADAM17-dependent
      transforming growth factor-alpha shedding.
AB  - Epidermal growth factor receptor (EGFR) activation by GPCRs regulates many
      important biological processes. ADAM metalloprotease activity has been implicated
      as a key step in transactivation, yet the regulatory mechanisms are not fully
      understood. Here, we investigate the regulation of transforming growth factor
      alpha (TGF-alpha) shedding by reactive oxygen species (ROS) through the ATP
      dependent activation of the P2Y family of GPCRs. We report that ATP stimulates
      TGF-alpha proteolysis with concomitant EGFR activation and that this process
      requires TACE/ADAM17 activity in both murine fibroblasts and CHO cells. ATP
      induced TGF-alpha shedding required calcium and was independent of Src family
      kinases and PKC and MAPK signaling. Moreover, ATP-induced TGF-alpha shedding was
      completely inhibited by scavengers of ROS, whereas calcium-stimulated shedding
      was partially inhibited by ROS scavenging. Hydrogen peroxide restored TGF-alpha
      shedding after calcium chelation. Importantly, we also found that ATP-induced
      shedding was independent of the cytoplasmic NADPH oxidase complex. Instead,
      mitochondrial ROS production increased in response to ATP and mitochondrial
      oxidative complex activity was required to activate TACE-dependent shedding.
      These results reveal an essential role for mitochondrial ROS in regulating GPCR
      induced growth factor shedding.

PMID- 19846670
TI  - The early host innate immune response to duck hepatitis B virus infection.
AB  - The early phase after hepatitis B virus infection could play a crucial role in
      clearance and/or persistence of the virus, particularly in neonates. This work
      compared the early phase of duck hepatitis B virus infection in 1-day-old (D1)
      and 28-day-old (D28) ducks to determine whether differences in viral or host
      innate immune response can be related to the difference in outcome. In the first
      phase, almost immediately after inoculation, virus was taken up by components of
      the reticulo-endothelial systems, particularly liver-specific macrophages,
      Kupffer cells. Very early after infection, the induction of alpha interferon by
      infected hepatocytes occurred and was rapidly reinforced by recruitment of
      effector lymphocytes, which directly or indirectly caused apoptosis, eliminating
      infected hepatocytes, as was seen in mature birds. In addition, a lack of
      lymphocytic infiltration of the liver was found in D1 ducks, which supports the
      suggestion that the innate immune network is less effective in D1 ducks. Taken
      together, these results suggest that failure of the co-ordinated innate immune
      response rather than a defect in induced antiviral cell-mediated immunity may be
      the key factor which makes baby ducks vulnerable to persistence of hepadnavirus
      infection.

PMID- 19846671
TI  - The genome of cyprinid herpesvirus 3 encodes 40 proteins incorporated in mature
      virions.
AB  - Koi herpesvirus, also known as cyprinid herpesvirus 3 (CyHV-3), is the
      aetiological agent of an emerging and mortal disease in common and koi carp. CyHV
      3 virions present the characteristic morphology of other members of the order
      Herpesvirales, being composed of an envelope, a capsid containing the genome and
      a tegument. This study identified CyHV-3 structural proteins and the
      corresponding encoding genes using liquid chromatography tandem mass spectrometry
      based proteomic approaches. In addition, exponentially modified protein abundance
      index analyses were used to estimate the relative abundance of the identified
      proteins in CyHV-3 virions. These analyses resulted in the identification of 40
      structural proteins, which were classified based on bioinformatic analyses as
      capsid (three), envelope (13), tegument (two) and unclassified (22) structural
      proteins. Finally, a search for host proteins in purified CyHV-3 virions
      indicated the potential incorporation of up to 18 distinct cellular proteins. The
      identification of the proteins incorporated into CyHV-3 virions and determination
      of the viral genes encoding these proteins are key milestones for further
      fundamental and applied research on this virus.

PMID- 19846672
TI  - ISG15, a ubiquitin-like interferon-stimulated gene, promotes hepatitis C virus
      production in vitro: implications for chronic infection and response to
      treatment.
AB  - Upregulation of interferon (IFN)-stimulated genes (ISGs), including IFN
      stimulated gene 15 (ISG15) and other members of the ISG15 pathway, in pre
      treatment liver tissue of patients chronically infected with hepatitis C virus
      (HCV) is associated with subsequent treatment failure (pegylated IFN
      alpha/ribavirin). This study assessed the effect of ISG15 on HCV production in
      vitro. The levels of ISG15 and of its conjugation to target proteins (ISGylation)
      were increased by plasmid transfection, but ISGylation was inhibited by small
      interfering RNA directed against the E1 activating enzyme, Ube1L, in Huh7.5
      cells. Cells were infected with HCV FL-J6/JFH virus, and HCV RNA and viral titres
      were determined. Levels of both HCV RNA and virus increased when levels of ISG15
      and ISGylation were increased, and decreased when ISGylation was inhibited. The
      effects of ISGylation on HCV were independent of upstream IFN signalling: IFN
      alpha-induced ISG expression was not altered by Ube1L knockdown. Thus, although
      ISG15 has antiviral activity against most viruses, ISG15 promotes HCV production.
      HCV might exploit ISG15 as a host immune evasion mechanism, and this may in part
      explain how increased expression of ISGs, especially ISG15, correlates with
      subsequent IFN-based treatment failure.

PMID- 19846673
TI  - Hepatitis C virus NS5A protein interacts with beta-catenin and stimulates its
      transcriptional activity in a phosphoinositide-3 kinase-dependent fashion.
AB  - Hepatitis C virus (HCV) infection is increasingly associated with the development
      of hepatocellular carcinoma (HCC). HCV is not thought to be directly oncogenic
      but, by modulating a range of cellular functions, may predispose patients to the
      development of liver tumours. However, the molecular mechanisms by which HCV
      infection might contribute to HCC remain to be characterized. In this regard, we
      showed previously that the HCV NS5A protein bound to the p85 regulatory subunit
      of phosphoinositide-3 kinase (PI3K), thereby stimulating the activity of the p110
      catalytic subunit of the enzyme. One of the downstream consequences of this was
      the stabilization of the proto-oncogene, beta-catenin, with a concomitant
      stimulation of its transcriptional activity. Here, we further analyse the
      mechanism by which NS5A mediates activation of beta-catenin. Although our
      previous data were consistent with a role for the PI3K downstream effector
      kinases, Akt and glycogen synthase kinase-3beta, in NS5A-mediated activation of
      beta-catenin, we demonstrate here that it is in fact independent of both of these
      kinases. Truncation analysis revealed that both the N and C termini of NS5A are
      required for full activation of beta-catenin. Furthermore, we demonstrate that
      NS5A, either alone or in complex with p85, is able to bind directly to beta
      catenin; again both N and C termini contribute to this interaction. We propose
      that NS5A activates beta-catenin via a novel mechanism that involves a direct
      interaction between the two proteins and is augmented by PI3K activity. This may
      contribute to the association between chronic HCV infection and the development
      of HCC.

PMID- 19846674
TI  - Molecular epidemiology and genetic diversity of hepatitis B virus genotype E in
      an isolated Afro-Colombian community.
AB  - Hepatitis B virus (HBV) infection is a significant public health concern with 350
      million chronic carriers worldwide. Eight HBV genotypes (A-H) have been described
      so far. Genotype E (HBV/E) is widely distributed in West Africa and has rarely
      been found in other continents, except for a few cases in individuals with an
      African background. In this study, we characterized HBV genotypes in Quibdo,
      Colombia, by partial S/P gene sequencing, and found, for the first time, HBV/E
      circulating in nine Afro-Colombian patients who had no recent contact with
      Africa. The presence of HBV/E in this community as a monophyletic group suggests
      that it was a result of a recent introduction by some Afro-descendent contact or,
      alternatively, that the virus came with slaves brought to Colombia. By using
      sequences with sampling dates, we estimated the substitution rate to be about 3.2
      x 10(-4) substitutions per site per year, which resulted in a time to the most
      recent common ancestor (TMRCA) of 29 years. In parallel, we also estimated the
      TMRCA for HBV/E by using two previously estimated substitution rates (7.7 x 10(
      4) and 1.5 x 10(-5) substitutions per site per year). The TMRCA was around 35
      years under the higher rate and 1500 years under the slower rate. In sum, this
      work reports for the first time the presence of an exclusively African HBV
      genotype circulating in South America. We also discuss the time of the entry of
      this virus into America based on different substitution rates estimated for HBV.

PMID- 19846675
TI  - Viral host-range factor C7 or K1 is essential for modified vaccinia virus Ankara
      late gene expression in human and murine cells, irrespective of their capacity to
      inhibit protein kinase R-mediated phosphorylation of eukaryotic translation
      initiation factor 2alpha.
AB  - Vaccinia virus (VACV) infection induces phosphorylation of eukaryotic translation
      initiation factor 2alpha (eIF2alpha), which inhibits cellular and viral protein
      synthesis. In turn, VACV has evolved the capacity to antagonize this antiviral
      response by expressing the viral host-range proteins K3 and E3. This study
      revealed that the host-range genes K1L and C7L also prevent eIF2alpha
      phosphorylation in modified VACV Ankara (MVA) infection of several human and
      murine cell lines. Moreover, C7L-deleted MVA (MVA-DeltaC7L) lacked late gene
      expression, which could be rescued by the function of host-range factor K1 or C7.
      It was demonstrated that viral gene expression was blocked after viral DNA
      replication and that it was independent of apoptosis induction. Furthermore, it
      was found that eIF2alpha phosphorylation in MVA-DeltaC7L-infected cells is
      mediated by protein kinase R (PKR) as shown in murine embryonic fibroblasts
      lacking PKR function, and it was shown that this was not due to reduced E3L gene
      expression. The block of eIF2alpha phosphorylation by C7 could be complemented by
      K1 in cells infected with MVA-DeltaC7L encoding a reinserted K1L gene (MVA
      DeltaC7L-K1L). Importantly, these data illustrated that eIF2alpha phosphorylation
      by PKR is not responsible for the block of late viral gene expression. This
      suggests that other mechanisms targeted by C7 and K1 are essential for completing
      the MVA gene expression cycle and probably also for VACV replication in a diverse
      set of cell types.

PMID- 19846676
TI  - Characterization of a rare natural intertypic type 2/type 3 penta-recombinant
      vaccine-derived poliovirus isolated from a child with acute flaccid paralysis.
AB  - A type 2 vaccine-derived poliovirus (VDPV) (strain CHN1025), with a 1.1 %
      (10/903) difference from Sabin strain in the VP1 coding region, was isolated from
      a child with poliomyelitis caused by a poliovirus variant infection. The patient
      was from Shandong Province of China and developed acute flaccid paralysis in
      1997. The child was infected with a rare and complicated penta-recombinant
      poliovirus with the uncommon genomic recombinant organization S2/S3/S1/S3/S1/S3.
      At least five successive rounds of recombination occurred in the VP1 capsid
      coding region and in the 2C, 3C (twice) and 3D(pol) non-capsid coding regions,
      respectively, during virus evolution. Strain CHN1025 had most of the
      characteristics of the type 2 vaccine strain; it had Sabin-specific epitopes,
      suggesting that the virus was antigenically indistinguishable from the Sabin 2
      reference strain. Typical mutations in the 5'-untranslated region and VP1
      associated with reversion to neurovirulence for Sabin 2 poliovirus were found,
      and the virus showed moderate neurovirulence in transgenic mice. A few nucleotide
      substitutions were located in the donor sequences, and two donor sequences
      contained no nucleotide substitutions, suggesting that these sequences were
      relatively new. The appearance of these mutations within approximately 192 days
      of at least five successive rounds of recombination events derived from a single
      ancestral infection illustrates the rapid emergence of new recombinants among
      VDPVs. This is the first report on the isolation of a type 2/type 3 poliovirus
      capsid recombinant with one of the five crossover sites located in the VP1 coding
      region.

PMID- 19846677
TI  - Parvovirus PARV4 visualization and detection.
AB  - The parvovirus PARV4 is the most recently described member of the family
      Parvoviridae that has a human host. To investigate the prevalence of PARV4 in
      blood, a quantitative TaqMan PCR was developed and plasma, sera or whole blood
      from a variety of population groups were examined. Eight samples were positive
      for PARV4, one at high copy number. The high-titre-positive plasma had an
      approximate viral load of 5 x 10(8) genome equivalents ml(-1). Two human sera,
      identified as PARV4 antibody-positive by indirect immunofluorescence, were used
      in immune electron microscopy to try to visualize native PARV4 within the high
      titre human plasma. PARV4 particles were observed using one of these two sera. To
      our knowledge, this is the first time that native PARV4 has been visualized.

PMID- 19846678
TI  - Differential binding patterns to host cells associated with particles of several
      human alphapapillomavirus types.
AB  - The focus of this research was to compare the binding profiles of human
      papillomavirus (HPV) 11, 16, 18 and 45 virus-like particles (VLPs) to HaCaT cells
      and to the extracellular matrix (ECM) secreted by these cells. All four HPV types
      tested bind to a component(s) of the ECM. HPV11 VLP binding is blocked when the
      ECM is pretreated with an anti-laminin 5 (LN5) polyclonal antibody. A series of
      treatments utilizing heparins and heparinase revealed that HPV18 VLPs are
      dependent on heparan sulfates (HS) for binding to cells and ECM. HPV16 and HPV45
      VLPs are dependent on HS for binding to HaCaT cells and dependent on both HS and
      LN5 for binding to ECM. These studies emphasize the need to study the binding
      characteristics of different HPV types before applying universal binding
      principles to all papillomaviruses.

PMID- 19846679
TI  - Immunologic paradox in the diagnosis of tuberculous meningitis.
AB  - We report a patient with microbiologically documented tuberculous meningitis
      showing that the therapeutic paradox, a therapy-induced switch to a neutrophil
      predominant situation in the differential cell counts of cerebrospinal fluid
      specimens, had a correlation with an immunologic paradox, an increased
      Mycobacterium tuberculosis-specific gamma interferon-producing T-cell response.

PMID- 19846680
TI  - Experimental infection of reindeer with cervid herpesvirus 2.
AB  - Cervid herpesvirus 2 (CvHV2) has been isolated from reindeer (Rangifer tarandus
      tarandus), and serological data indicate that in reindeer this virus is endemic
      in Fennoscandia, Alaska, Canada, and Greenland. CvHV2 has been described as a
      cause of subclinical genital infections in reindeer, but little information on
      primary infections exists. In this study, six seronegative and presumably
      pregnant reindeer were allocated to one of two groups. Two animals were
      inoculated with CvHV2 intratracheally, and two animals intravaginally, with one
      control animal in each group receiving sterile water. Mild hyperthermia and
      serous discharges from the vagina and nose were observed. No abortions were
      recorded, but one calf died shortly after birth. Inoculated animals seroconverted
      and had neutralizing antibodies after days 7 to 10 postinfection. CvHV2 was
      detected by PCR in nasal and vaginal swabs from animals in both groups but could
      be isolated only from nasal swabs in the respiratory group and from vaginal swabs
      in the genital group. CvHV2 was detected by PCR in various organs and tissues
      postmortem. In control animals, the virus could not be isolated in spite of PCR
      positive nasal and vaginal swab samples and some degree of positive
      immunostaining. One of the animals that were inoculated intratracheally developed
      a hemorrhagic, necrotizing bronchopneumonia, which was CvHV2 positive by PCR and
      immunohistochemistry. We conclude that CvHV2 can cause systemic infection, that
      both genital and respiratory inoculations can lead to virus shedding, and that
      the virus can infect the fetus in utero.

PMID- 19846682
TI  - The effects of school garden experiences on middle school-aged students'
      knowledge, attitudes, and behaviors associated with vegetable consumption.
AB  - This study describes the effects of garden-based education on children's
      vegetable consumption. As part of a pre-post panel study, 236 students complete
      the Garden Vegetable Frequency Questionnaire and 161 complete a taste test.
      Results indicate that school gardening may affect children's vegetable
      consumption, including improved recognition of, attitudes toward, preferences
      for, and willingness to taste vegetables. Gardening also increases the variety of
      vegetables eaten. Future research should explore whether effects persist over
      time and if and how changes in children's behavior affect the behavior of their
      caregivers. Implications of study findings for policy and practice are discussed.
      Suggestions for applying results to future health promotions are provided.

PMID- 19846681
TI  - Monocyte-derived interleukin-10 depresses the Bordetella pertussis- specific
      gamma interferon response in vaccinated infants.
AB  - Antigen-specific gamma interferon (IFN-gamma) has been demonstrated to
      participate in protection against Bordetella pertussis infection. Circulating
      mononuclear cells from B. pertussis-infected and from pertussis-vaccinated
      infants secrete high amounts of IFN-gamma after in vitro stimulation by B.
      pertussis antigens, but with a large variation in the secreted IFN-gamma levels
      between individuals. We show here that the inhibition of the specific IFN-gamma
      response can be at least partially attributed to IL-10 secretion by monocytes.
      This IL-10 secretion was not associated with polymorphisms at positions -1082, 
      819, and -592 of the IL-10 gene promoter, suggesting that other genetic or
      environmental factors affect IL-10 expression and secretion.

PMID- 19846683
TI  - The effect of multisensory stimulation on persons residing in an extended care
      facility.
AB  - BACKGROUND: Non-pharmacological interventions, such as multisensory stimulation
      environments (MSSE), have demonstrated the ability to reduce inappropriate
      behavior among individuals with Alzheimer's disease. METHODS: In this study, we
      compared the incidences of problematic behavior among individuals with
      Alzheimer's disease residing in a long-term care facility who were and were not
      exposed to an MSSE. Retrospective data were obtained using the Psychotic Behavior
      Assessment Record (PBAR), mandated by Medicare to be used when antipsychotic
      medications are administered. Psychotic Behavior Assessment Record data were
      collected using the first and sixth month of admission for residents after
      appropriate consent was secured. RESULTS: Documented disruptive behavior included
      pacing, exit-seeking activities, hitting, yelling, and aggressive talking. The
      use of the MSSE resulted in a decrease in the number of incidences of disruptive
      behavior, but not the behaviors present. CONCLUSION: The use of MSSE, as a non
      pharmacological intervention, demonstrates the ability to decrease the number of
      incidences of disruptive or problematic behavior. The use of these interventions,
      where feasible, should be considered prior to the use of pharmacological methods.

PMID- 19846684
TI  - The power of Mom in communicating health.

PMID- 19846685
TI  - Social marketing and health communication: from people to places.

PMID- 19846686
TI  - The effect of less-lethal weapons on injuries in police use-of-force events.
AB  - OBJECTIVES: We investigated the effect of the use of less-lethal weapons,
      conductive energy devices (CEDs), and oleoresin capsicum (OC) spray on the
      prevalence and incidence of injuries to police officers and civilians in
      encounters involving the use of force. METHODS: We analyzed data from 12 police
      departments that documented injuries to officers and civilians in 24,380 cases.
      We examined monthly injury rates for 2 police departments before and after their
      adoption of CEDs. RESULTS: Odds of injury to civilians and officers were
      significantly lower when police used CED weapons, after control for differences
      in case attributes and departmental policies restricting use of these weapons.
      Monthly incidence of injury in 2 police departments declined significantly, by
      25% to 62%, after adoption of CED devices. CONCLUSIONS: Injuries sustained during
      police use-of-force events affect thousands of police officers and civilians in
      the United States each year. Incidence of these injuries can be reduced
      dramatically when law enforcement agencies responsibly employ less-lethal weapons
      in lieu of physical force.

PMID- 19846687
TI  - Risk of alcohol-impaired driving recidivism among first offenders and multiple
      offenders.
AB  - OBJECTIVES: We sought to determine the statewide impact of having prior alcohol
      impaired driving violations of any type on the rate of first occurrence or
      recidivism among drivers with 0, 1, 2, or 3 or more prior violations in Maryland.
      METHODS: We analyzed more than 100 million driver records from 1973 to 2004 and
      classified all Maryland drivers into 4 groups: those with 0, 1, 2, or 3 or more
      prior violations. The violation rates for approximately 21 million drivers in
      these 4 groups were compared for the study period 1999 to 2004. RESULTS: On
      average, there were 3.4, 24.3, 35.9, and 50.8 violations per 1000 drivers a year
      among those with 0, 1, 2, or 3 or more priors, respectively. The relative risks
      for men compared with women among these groups of drivers were 3.8, 1.2, 1.0, and
      1.0, respectively. CONCLUSIONS: The recidivism rate among first offenders more
      closely resembles that of second offenders than of nonoffenders. Men and women
      are at equal risk of recidivating once they have had a first violation
      documented. Any alcohol-impaired driving violation, not just convictions, is a
      marker for future recidivism.

PMID- 19846688
TI  - Changes in skin tanning attitudes. Fashion articles and advertisements in the
      early 20th century.
AB  - Historical reviews suggest that tanning first became fashionable in the 1920s or
      1930s. To quantitatively and qualitatively examine changes in tanning attitudes
      portrayed in the popular women's press during the early 20th century, we reviewed
      summer issues of Vogue and Harper's Bazaar for the years 1920, 1927, 1928, and
      1929. We examined these issues for articles and advertisements promoting skin
      tanning or skin bleaching and protection. We found that articles and
      advertisements promoting the fashionable aspects of tanned skin were more
      numerous in 1928 and 1929 than in 1927 and 1920, whereas those promoting pale
      skin (by bleaching or protection) were less numerous. These findings demonstrate
      a clear shift in attitudes toward tanned skin during this period.

PMID- 19846689
TI  - Race and unhealthy behaviors: chronic stress, the HPA axis, and physical and
      mental health disparities over the life course.
AB  - OBJECTIVES: We sought to determine whether unhealthy behaviors play a stress
      buffering role in observed racial disparities in physical and mental health.
      METHODS: We conducted logistic regressions by race on data from the first 2 waves
      of the Americans' Changing Lives Survey to determine whether unhealthy behaviors
      had buffering effects on the relationship between major stressors and chronic
      health conditions, and on the relationship between major stressors and meeting
      the criteria for major depression. RESULTS: Among Whites, unhealthy behaviors
      strengthened the relationship between stressors and meeting major-depression
      criteria. Among Blacks, however, the relationship between stressors and meeting
      major-depression criteria was stronger among those who had not engaged in
      unhealthy behaviors than among those who had. Among both race groups there was a
      positive association between stressors and chronic health conditions. Among
      Blacks there was an additional positive association between number of unhealthy
      behaviors and number of chronic conditions. CONCLUSIONS: Those who live in
      chronically stressful environments often cope with stressors by engaging in
      unhealthy behaviors that may have protective mental-health effects. However, such
      unhealthy behaviors can combine with negative environmental conditions to
      eventually contribute to morbidity and mortality disparities among social groups.

PMID- 19846690
TI  - Socioeconomic status and body mass index among Hispanic children of immigrants
      and children of natives.
AB  - OBJECTIVES: We examined how Hispanic parents' income and education, combined with
      their nativity status, influenced the body mass index (BMI) of their children,
      compared with non-Hispanic White children and their parents. METHODS: We used
      data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-99
      to estimate linear growth curve models of children's initial BMI in kindergarten
      and change in BMI through fifth grade. Socioeconomic status was measured by
      logged household income and parental educational attainment (less than high
      school, high school graduate, some college, college graduate or higher). RESULTS:
      Parental education was negatively associated with children's BMI (baseline and
      growth) for non-Hispanic White children. Among Hispanic children, the association
      of parental education with growth in BMI was negative but much weaker. The weak
      effect of parental education was not explained by the presence of immigrants in
      the Hispanic population. Income was strongly negatively associated with
      children's BMI in kindergarten among children of Hispanic and White natives, but
      positively associated among Hispanic immigrant families. CONCLUSIONS: The
      positive income-BMI association among Hispanic immigrant children might reflect
      cultural differences that immigrant parents carry with them from their countries
      of origin.

PMID- 19846691
TI  - Zonal chondrocyte subpopulations reacquire zone-specific characteristics during
      in vitro redifferentiation.
AB  - BACKGROUND: If chondrocytes from the superficial, middle, and deep zones of
      articular cartilage could maintain or regain their characteristic properties
      during in vitro culture, it would be feasible to create constructs comprising
      these distinctive zones. HYPOTHESIS: Zone-specific characteristics of zonal cell
      populations will disappear during 2-dimensional expansion but will reappear after
      3-dimensional redifferentiation, independent of the culture technique used
      (alginate beads versus pellet culture). STUDY DESIGN: Controlled laboratory
      study. METHODS: Equine articular chondrocytes from the 3 zones were expanded in
      monolayer culture (8 donors) and subsequently redifferentiated in pellet and
      alginate bead cultures for up to 4 weeks. Glycosaminoglycans and DNA were
      quantified, along with immunohistochemical assessment of the expression of
      various zonal markers, including cartilage oligomeric protein (marking cells from
      the deeper zones) and clusterin (specifically expressed by superficial
      chondrocytes). RESULTS: Cell yield varied between zones, but proliferation rates
      did not show significant differences. Expression of all evaluated zonal markers
      was lost during expansion. Compared to the alginate bead cultures, pellet
      cultures showed a higher amount of glycosaminoglycans produced per DNA after
      redifferentiation. In contrast to cells in pellet cultures, cells in alginate
      beads regained zonal differences, as evidenced by zone-specific reappearance of
      cartilage oligomeric protein and clusterin, as well as significantly higher
      glycosaminoglycans production by cells from the deep zone compared to the
      superficial zone. CONCLUSION: Chondrocytes isolated from the 3 zones of equine
      cartilage can restore their zone-specific matrix expression when cultured in
      alginate after in vitro expansion. CLINICAL RELEVANCE: Appreciation of the zonal
      differences can lead to important advances in cartilage tissue engineering.
      Findings support the use of hydrogels such as alginate for engineering zonal
      cartilage constructs.

PMID- 19846692
TI  - Shallow medial tibial plateau and steep medial and lateral tibial slopes: new
      risk factors for anterior cruciate ligament injuries.
AB  - BACKGROUND: The geometry of the tibial plateau has been largely ignored as a
      source of possible risk factors for anterior cruciate ligament injury.
      Discovering the anterior cruciate ligament injury risk factors associated with
      the tibial plateau may lead to delineation of the existing sex-based disparity in
      anterior cruciate ligament injuries and help develop strategies for the
      prevention of anterior cruciate ligament injuries regardless of gender.
      HYPOTHESIS: Individuals with a shallower medial tibial depth of concavity, while
      having increased posteriorly directed slope of their tibial plateau, are at
      increased risk of suffering an anterior cruciate ligament injury compared with
      those with decreased posterior slope and increased medial tibial depth.
      Furthermore, these relationships are different between men and women. STUDY
      DESIGN: Case-control study (prevalence); Level of evidence, 3. METHODS: The
      medial, lateral, and coronal tibial plateau slopes as well as the medial tibial
      depth of concavity in 55 uninjured controls (33 women and 22 men) and 49 anterior
      cruciate ligament-injured cases (27 women and 22 men) were measured using
      magnetic resonance images. First, a preliminary t test was performed to establish
      any existing differences between groups. Next, a logistic regression model was
      developed to determine the probability of anterior cruciate ligament injury in an
      individual based on the measured covariates. RESULTS: The female anterior
      cruciate ligament-injured cases had increased lateral tibial slope (P = .03) and
      shallower medial tibial depth (P = .0003) compared with the uninjured controls,
      while male cases had increased lateral and medial tibial slope (P = .02) and
      shallower medial tibial depth (P = .0004) compared with controls. The logistic
      regression analysis and odds ratio estimates showed that medial tibial depth is
      an important risk factor (odds ratio = 3.03 per 1 mm decrease in its value),
      followed by lateral tibial slope (odds ratio = 1.17 per 1 degrees increase in its
      value) in all participants. The medial tibial slope (odds ratio = 1.18 per 1
      degrees increase in its value) was a risk factor only in men. CONCLUSION: A
      combination of increased posterior-directed tibial plateau slope and shallow
      medial tibial plateau depth could be a major risk factor in anterior cruciate
      ligament injury susceptibility regardless of gender. Different injury risk models
      may be needed for men and women as other key risk factors are identified.

PMID- 19846693
TI  - Effect of accelerated weightbearing after matrix-associated autologous
      chondrocyte implantation on the femoral condyle on radiographic and clinical
      outcome after 2 years: a prospective, randomized controlled pilot study.
AB  - BACKGROUND: There is no consensus about the optimal time for weightbearing
      activities after matrix-associated autologous chondrocyte implantation (MACI) of
      the femoral condyle. HYPOTHESIS: A comprehensive protocol after MACI on the
      femoral condyle with accelerated weightbearing leads to a better functional and
      radiographic outcome compared with the same comprehensive protocol with delayed
      weightbearing. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.
      METHODS: Thirty-one patients (22 male, 9 female) after MACI on the femoral
      condyle were randomly assigned to the accelerated weightbearing group (group A)
      or the delayed weightbearing group (group B). Aside from increase and time of
      full weightbearing, both groups adhered to the same rehabilitation protocol and
      exercises. Patients were assessed preoperatively and at 4, 12, 24, 52, and 104
      weeks after surgery. Clinical evaluation was performed by determining the
      subjective form of the International Knee Documentation Committee (IKDC), the
      Tegner activity scale, and the Knee Injury and Osteoarthritis Outcome Score
      (KOOS). Radiological outcome was evaluated by the MOCART score and the size and
      amount of bone marrow edema and effusion. RESULTS: In both groups, there were no
      differences with regard to the clinical outcome. For the radiological outcome,
      group A showed a higher prevalence of bone marrow edema after 6 months without
      correlation to the clinical outcome (P = .06-.1). However, after 104 weeks, there
      were no differences in the radiological outcome between group A and group B.
      CONCLUSION: A rehabilitation protocol with accelerated weightbearing leads to
      good clinical and functional outcome after 2 years without jeopardizing the
      healing graft.

PMID- 19846694
TI  - Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte
      implantation results in better clinical outcome at 36 months in a randomized
      trial compared to microfracture.
AB  - BACKGROUND: Damaged articular cartilage has limited capacity for self-repair.
      Autologous chondrocyte implantation using a characterized cell therapy product
      results in significantly better early structural repair as compared with
      microfracture in patients with symptomatic joint surface defects of the femoral
      condyles of the knee. PURPOSE: To evaluate clinical outcome at 36 months after
      characterized chondrocyte implantation (CCI) versus microfracture (MF). STUDY
      DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients aged
      18 to 50 years with single International Cartilage Repair Society (ICRS) grade
      III/IV symptomatic cartilage defects of the femoral condyles were randomized to
      CCI (n = 57) or MF (n = 61). Clinical outcome was measured over 36 months by the
      Knee injury and Osteoarthritis Outcome Score (KOOS). Serial magnetic resonance
      imaging (MRI) scans were scored using the Magnetic resonance Observation of
      Cartilage Repair Tissue (MOCART) system and 9 additional items. Gene expression
      profile scores associated with ectopic cartilage formation were determined by RT
      PCR. RESULTS: Baseline mean overall KOOS (+/-SE) was comparable between the CCI
      and MF groups (56.30 +/- 1.91 vs 59.46 +/- 1.98, respectively). Mean improvement
      (+/-SE) from baseline to 36 months in overall KOOS was greater in the CCI group
      than the MF group (21.25 +/- 3.60 vs 15.83 +/- 3.48, respectively), while in a
      mixed linear model analysis with time as a categorical variable, significant
      differences favoring CCI were shown in overall KOOS (P = .048) and the subdomains
      of Pain (P = .044) and QoL (P = .036). More CCI- than MF-treated patients were
      treatment responders (83% vs 62%, respectively). In patients with symptom onset
      of <2 years, the mean improvement (+/-SE) from baseline to 36 months in overall
      KOOS was greater with CCI than MF (24.98 +/- 4.34 vs 16.50 +/- 3.99,
      respectively) and even greater in patients with symptom onset of <3 years (26.08
      +/- 4.10 vs 17.09 +/- 3.77, respectively). Characterized chondrocyte implantation
      patients with high (> or =2) versus low (<2) gene profile scores showed greater
      improvement from baseline in mean overall KOOS (+/-SE) at 36 months (28.91 +/-
      5.69 vs 18.18 +/- 5.08, respectively). Subchondral bone reaction significantly
      worsened over time with MF compared with CCI (P <.05). CONCLUSION: Characterized
      chondrocyte implantation for the treatment of articular cartilage defects of the
      femoral condyles of the knee results in significantly better clinical outcome at
      36 months in a randomized trial compared with MF. Time to treatment and
      chondrocyte quality were shown to affect outcome.

PMID- 19846695
TI  - EphB maintains dendritic spine morphology through focal adhesion kinase.

PMID- 19846696
TI  - The necessity of NKCC1: loss of the chloride cotransporter in a knock-out model
      and potential compensatory mechanisms.

PMID- 19846697
TI  - Nonlinear integration of visual and haltere inputs in fly neck motor neurons.
AB  - Animals use information from multiple sensory organs to generate appropriate
      behavior. Exactly how these different sensory inputs are fused at the motor
      system is not well understood. Here we study how fly neck motor neurons integrate
      information from two well characterized sensory systems: visual information from
      the compound eye and gyroscopic information from the mechanosensory halteres.
      Extracellular recordings reveal that a subpopulation of neck motor neurons
      display "gating-like" behavior: they do not fire action potentials in response to
      visual stimuli alone but will do so if the halteres are coactivated.
      Intracellular recordings show that these motor neurons receive small, sustained
      subthreshold visual inputs in addition to larger inputs that are phase locked to
      haltere movements. Our results suggest that the nonlinear gating-like effect
      results from summation of these two inputs with the action potential threshold
      providing the nonlinearity. As a result of this summation, the sustained visual
      depolarization is transformed into a temporally structured train of action
      potentials synchronized to the haltere beating movements. This simple mechanism
      efficiently fuses two different sensory signals and may also explain the context
      dependent effects of visual inputs on fly behavior.

PMID- 19846698
TI  - T-type calcium channel inhibition underlies the analgesic effects of the
      endogenous lipoamino acids.
AB  - Lipoamino acids are anandamide-related endogenous molecules that induce analgesia
      via unresolved mechanisms. Here, we provide evidence that the T-type/Cav3 calcium
      channels are important pharmacological targets underlying their physiological
      effects. Various lipoamino acids, including N-arachidonoyl glycine (NAGly),
      reversibly inhibited Cav3.1, Cav3.2, and Cav3.3 currents, with potent effects on
      Cav3.2 [EC(50) approximately 200 nm for N-arachidonoyl 3-OH-gamma-aminobutyric
      acid (NAGABA-OH)]. This inhibition involved a large shift in the Cav3.2 steady
      state inactivation and persisted during fatty acid amide hydrolase (FAAH)
      inhibition as well as in cell-free outside-out patch. In contrast, lipoamino
      acids had weak effects on high-voltage-activated (HVA) Cav1.2 and Cav2.2 calcium
      currents, on Nav1.7 and Nav1.8 sodium currents, and on anandamide-sensitive TRPV1
      and TASK1 currents. Accordingly, lipoamino acids strongly inhibited native Cav3.2
      currents in sensory neurons with small effects on sodium and HVA calcium
      currents. In addition, we demonstrate here that lipoamino acids NAGly and NAGABA
      OH produced a strong thermal analgesia and that these effects (but not those of
      morphine) were abolished in Cav3.2 knock-out mice. Collectively, our data
      revealed lipoamino acids as a family of endogenous T-type channel inhibitors,
      suggesting that these ligands can modulate multiple cell functions via this newly
      evidenced regulation.

PMID- 19846699
TI  - Functional recovery after lesion of a central pattern generator.
AB  - In cases of neuronal injury when regeneration is restricted, functional recovery
      can occur through reorganization of the remaining neural circuitry. We found an
      example of such recovery in the central pattern generator (CPG) for the escape
      swim of the mollusc Tritonia diomedea. The CPG neurons are bilaterally
      represented and each neuron projects an axon through one of two pedal
      commissures. Cutting the posterior pedal commissure [pedal nerve 6 (PdN6)] in the
      animal or in the isolated brain caused a deficit in the swim behavior and in the
      fictive motor pattern, respectively, each of which recovered over the course of
      20 h. Locally blocking spiking activity in PdN6 with sodium-free saline and/or
      tetrodotoxin disrupted the motor pattern in a reversible manner. Maintained
      blockade of PdN6 led to a functional recovery of the swim motor pattern similar
      to that observed in response to cutting the commissure. Among the CPG neurons,
      cerebral neuron 2 (C2) makes functional connection onto the ventral swim
      interneuron-B (VSI) in both pedal ganglia. Cutting or blocking PdN6 eliminated C2
      evoked excitation of VSI in the pedal ganglion distal to the lesion. Associated
      with the recovery of the swim motor pattern, the synaptic action of C2 onto VSI
      in the proximal pedal ganglion changed from being predominantly inhibitory to
      being predominantly excitatory. These results show that the Tritonia swim CPG
      undergoes adaptive plasticity in response to the loss of critical synaptic
      connections; reversal of synaptic action in the CPG may be at least partially
      responsible for this functional recovery.

PMID- 19846700
TI  - Grafting neural precursor cells promotes functional recovery in an SCA1 mouse
      model.
AB  - The B05 transgenic SCA1 mice, expressing human ataxin-1 with an expanded
      polyglutamine tract in cerebellar Purkinje cells (PCs), recapitulate many
      pathological and behavioral characteristics of the neurodegenerative disease
      spinocerebellar ataxia type 1 (SCA1), including progressive ataxia and PC loss.
      We transplanted neural precursor cells (NPCs) derived from the subventricular
      zone of GFP-expressing adult mice into the cerebellar white matter of SCA1 mice
      when they showed absent (5 weeks), initial (13 weeks), and significant (24 weeks)
      PC loss. Only in mice with significant cell loss, grafted NPCs migrated into the
      cerebellar cortex. These animals showed improved motor skills compared with sham
      treated controls. No grafted cell adopted the morphological and
      immunohistochemical characteristics of PCs, but the cerebellar cortex in NPC
      grafted SCA1 mice had a significantly thicker molecular layer and more surviving
      PCs. Perforated patch-clamp recordings revealed a normalization of the PC basal
      membrane potential, which was abnormally depolarized in sham-treated animals. No
      significant increase in levels of several neurotrophic factors was observed,
      suggesting, along with morphological observation, that the neuroprotective effect
      of grafted NPCs was mediated by direct contact with the host PCs. We postulate
      that a similar neuroprotective effect of NPCs may be applicable to other
      cerebellar degenerative diseases.

PMID- 19846702
TI  - Spatiotemporal distortions of visual perception at the time of saccades.
AB  - Both space and time are grossly distorted during saccades. Here we show that the
      two distortions are strongly linked, and that both could be a consequence of the
      transient remapping mechanisms that affect visual neurons perisaccadically. We
      measured perisaccadic spatial and temporal distortions simultaneously by asking
      subjects to report both the perceived spatial location of a perisaccadic vertical
      bar (relative to a remembered ruler), and its perceived timing (relative to two
      sounds straddling the bar). During fixation and well before or after saccades,
      bars were localized veridically in space and in time. In different epochs of the
      perisaccadic interval, temporal perception was subject to different biases. At
      about the time of the saccadic onset, bars were temporally mislocalized 50-100 ms
      later than their actual presentation and spatially mislocalized toward the
      saccadic target. Importantly, the magnitude of the temporal distortions co-varied
      with the spatial localization bias and the two phenomena had similar dynamics.
      Within a brief period about 50 ms before saccadic onset, stimuli were perceived
      with shorter latencies than at other delays relative to saccadic onset,
      suggesting that the perceived passage of time transiently inverted its direction.
      Based on this result we could predict the inversion of perceived temporal order
      for two briefly flashed visual stimuli. We developed a model that simulates the
      perisaccadic transient change of neuronal receptive fields predicting well the
      reported temporal distortions. The key aspects of the model are the dynamics of
      the "remapped" activity and the use of decoder operators that are optimal during
      fixation, but are not updated perisaccadically.

PMID- 19846701
TI  - Visual impairment in the absence of dystroglycan.
AB  - Ocular involvement in muscular dystrophy ranges from structural defects to
      abnormal electroretinograms. While the mechanisms underlying the abnormal retinal
      physiology in patients are not understood, it is thought that alpha-dystroglycan
      extracellular interactions are critical for normal visual function. Here we show
      that beta-dystroglycan anchors dystrophin and the inward rectifying K(+) channel
      Kir4.1 at glial endfeet and that disruption of dystrophin and potassium channel
      clustering in dystroglycan mutant mice is associated with an attenuation of the
      electroretinogram b-wave. Glial-specific inactivation of dystroglycan or deletion
      of the cytoplasmic domain of beta-dystroglycan was sufficient to attenuate the
      electroretinogram b-wave. Unexpectedly, deletion of the beta-dystroglycan
      cytoplasmic domain did not disrupt the laminar structure of the retina. In
      contrast to the role of alpha-dystroglycan extracellular interactions during
      early development of the CNS, beta-dystroglycan intracellular interactions are
      important for visual function but not the laminar development of the retina.

PMID- 19846703
TI  - Resolving response, decision, and strategic control: evidence for a functional
      topography in dorsomedial prefrontal cortex.
AB  - The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of
      cognitive control and decision making. Here, we provide evidence for an anterior
      to-posterior topography within the DMPFC using tasks that evoke three distinct
      forms of control demands--response, decision, and strategic--each of which could
      be mapped onto independent behavioral data. Specifically, we identify three
      spatially distinct regions within the DMPFC: a posterior region associated with
      control demands evoked by multiple incompatible responses, a middle region
      associated with control demands evoked by the relative desirability of decision
      options, and an anterior region that predicts control demands related to
      deviations from an individual's preferred decision-making strategy. These results
      provide new insight into the functional organization of DMPFC and suggest how
      recent controversies about its role in complex decision making and response
      mapping can be reconciled.

PMID- 19846705
TI  - Embedding multiple trajectories in simulated recurrent neural networks in a self
      organizing manner.
AB  - Complex neural dynamics produced by the recurrent architecture of neocortical
      circuits is critical to the cortex's computational power. However, the synaptic
      learning rules underlying the creation of stable propagation and reproducible
      neural trajectories within recurrent networks are not understood. Here, we
      examined synaptic learning rules with the goal of creating recurrent networks in
      which evoked activity would: (1) propagate throughout the entire network in
      response to a brief stimulus while avoiding runaway excitation; (2) exhibit
      spatially and temporally sparse dynamics; and (3) incorporate multiple neural
      trajectories, i.e., different input patterns should elicit distinct trajectories.
      We established that an unsupervised learning rule, termed presynaptic-dependent
      scaling (PSD), can achieve the proposed network dynamics. To quantify the
      structure of the trained networks, we developed a recurrence index, which
      revealed that presynaptic-dependent scaling generated a functionally feedforward
      network when training with a single stimulus. However, training the network with
      multiple input patterns established that: (1) multiple non-overlapping stable
      trajectories can be embedded in the network; and (2) the structure of the network
      became progressively more complex (recurrent) as the number of training patterns
      increased. In addition, we determined that PSD and spike-timing-dependent
      plasticity operating in parallel improved the ability of the network to
      incorporate multiple and less variable trajectories, but also shortened the
      duration of the neural trajectory. Together, these results establish one of the
      first learning rules that can embed multiple trajectories, each of which recruits
      all neurons, within recurrent neural networks in a self-organizing manner.

PMID- 19846704
TI  - Neural correlates of consonance, dissonance, and the hierarchy of musical pitch
      in the human brainstem.
AB  - Consonant and dissonant pitch relationships in music provide the foundation of
      melody and harmony, the building blocks of Western tonal music. We hypothesized
      that phase-locked neural activity within the brainstem may preserve information
      relevant to these important perceptual attributes of music. To this end, we
      measured brainstem frequency-following responses (FFRs) from nonmusicians in
      response to the dichotic presentation of nine musical intervals that varied in
      their degree of consonance and dissonance. Neural pitch salience was computed for
      each response using temporally based autocorrelation and harmonic pitch sieve
      analyses. Brainstem responses to consonant intervals were more robust and yielded
      stronger pitch salience than those to dissonant intervals. In addition, the
      ordering of neural pitch salience across musical intervals followed the
      hierarchical arrangement of pitch stipulated by Western music theory. Finally,
      pitch salience derived from neural data showed high correspondence with
      behavioral consonance judgments (r = 0.81). These results suggest that brainstem
      neural mechanisms mediating pitch processing show preferential encoding of
      consonant musical relationships and, furthermore, preserve the hierarchical pitch
      relationships found in music, even for individuals without formal musical
      training. We infer that the basic pitch relationships governing music may be
      rooted in low-level sensory processing and that an encoding scheme that favors
      consonant pitch relationships may be one reason why such intervals are preferred
      behaviorally.

PMID- 19846706
TI  - Exaggerated response of a vasopressin-enhanced green fluorescent protein
      transgene to nociceptive stimulation in the rat.
AB  - Nociceptive stimulation elicits neuroendocrine responses such as arginine
      vasopressin (AVP) release as well as activation of the hypothalamo-pituitary
      adrenal axis. We have generated novel transgenic rats expressing an AVP-enhanced
      green fluorescent protein (eGFP) fusion gene, and we examined the effects of
      nociceptive stimulation on transgene expression in the hypothalamus after
      subcutaneous injection of saline or formalin into the bilateral hindpaws in these
      rats. We have assessed (1) AVP levels in plasma and the changes of eGFP mRNA and
      AVP heteronuclear RNA (hnRNA) in the supraoptic nucleus (SON) and the
      paraventricular nucleus (PVN) using in situ hybridization histochemistry, (2)
      gene expression changes in distinct magnocellular and parvocellular divisions of
      the PVN, (3) eGFP fluorescence in the SON, the PVN, the median eminence (ME), and
      the posterior pituitary gland (PP). Plasma AVP levels were significantly
      increased 15 min after formalin injection. In the same time period, the AVP hnRNA
      levels in the PVN were increased, especially in the parvocellular division of the
      PVN in formalin-injected rats. In the same region, eGFP mRNA levels after
      formalin injection were also significantly increased to a much greater extent
      than those of AVP hnRNA. The eGFP fluorescence in the SON, the PVN, the ME, and
      the PP was markedly increased in formalin-injected rats and especially increased
      in the parvocellular divisions of the PVN. Together, our results demonstrate
      robust and rapid changes in the expression of the AVP-eGFP transgene in the rat
      hypothalamus after acute nociceptive stimulation.

PMID- 19846707
TI  - Muscle contractions guide rohon-beard peripheral sensory axons.
AB  - Multiple molecular cues guide neuronal axons to their targets during development.
      Previous studies in vitro have shown that mechanical stimulation also can affect
      axon growth; however, whether mechanical force contributes to axon guidance in
      vivo is unknown. We investigated the role of muscle contractions in the guidance
      of zebrafish peripheral Rohon-Beard (RB) sensory axons in vivo. We analyzed
      several mutants that affect muscle contraction through different molecular
      pathways, including a new mutant allele of the titin a (pik) gene, mutants that
      affect the hedgehog signaling pathway, and a nicotinic acetylcholine receptor
      mutant. We found RB axon defects in these mutants, the severity of which appeared
      to correlate with the extent of muscle contraction loss. These axons extend
      between the muscle and skin and normally have ventral trajectories and repel each
      other on contact. RB peripheral axons in muscle mutants extend longitudinally
      instead of ventrally, and the axons fail to repel one another on contact. In
      addition, we showed that limiting muscle movements by embedding embryos in
      agarose caused similar defects in peripheral RB axon guidance. This work suggests
      that the mechanical forces generated by muscle contractions are necessary for
      proper sensory axon pathfinding in vivo.

PMID- 19846709
TI  - Relationship between neural responses and visual grouping in the monkey parietal
      cortex.
AB  - Visual grouping through the binding of multiple discrete elements is an important
      component of object perception, and neurological studies have shown that the
      posterior parietal cortex plays a vital role in that process. To study the neural
      mechanisms underlying visual grouping, we recorded neuronal activity from the
      lateral bank of the intraparietal sulcus (L-IPS) of monkeys while they performed
      a task that required them to discriminate among rapidly presented visual patterns
      composed of five black or white dots arranged in a cross. The monkeys had to
      detect the patterns in which dots with the same contrast were arranged either
      horizontally or vertically (target). Visual grouping was necessary for detection
      of the target, and we surmised that if L-IPS neurons are involved in visual
      grouping, they may selectively respond to the grouped objects. In addition, we
      manipulated the monkeys' attention to the grouping of the elements. We found that
      many L-IPS neurons showed selectivity for the orientation of the target stimuli,
      and that selectivity was enhanced by the top-down attention. Moreover, the
      selectivity correlated with behavioral performance. These results provide the
      first physiological evidence that L-IPS neurons make a crucial contribution to
      visual grouping by combining visual and attentional signals so as to bind
      discrete visual elements together.

PMID- 19846708
TI  - Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of
      substantia gelatinosa neurons.
AB  - The Mas-related G-protein-coupled receptor D (Mrgprd) marks a distinct subset of
      sensory neurons that transmit polymodal nociceptive information from the skin
      epidermis to the substantia gelatinosa (SG, lamina II) of the spinal cord.
      Moreover, Mrgprd-expressing (Mrgprd(+)) neurons are required for the full
      expression of mechanical but not thermal nociception. While such anatomical and
      functional specificity suggests Mrgprd(+) neurons might synapse with specific
      postsynaptic targets in the SG, precisely how Mrgprd(+) neurons interface with
      spinal circuits is currently unknown. To study circuit connectivity, we
      genetically targeted the light-activated ion channel Channelrhodopsin-2-Venus
      (ChR2-Venus) to the Mrgprd locus. In these knock-in mice, ChR2-Venus was
      localized to nonpeptidergic Mrgprd(+) neurons and axons, while peptidergic
      CGRP(+) neurons were not significantly labeled. Dissociated Mrgprd(+) DRG neurons
      from mice expressing one or two copies of ChR2-Venus could be activated in vitro
      as evidenced by light-evoked currents and action potentials. In addition,
      illumination of Mrgprd-ChR2-Venus(+) axon terminals in spinal cord slices evoked
      EPSCs in half of all SG neurons. Within this subset, Mrgprd(+) neurons were
      monosynaptically connected to most known classes of SG neurons, including radial,
      tonic central, transient central, vertical, and antenna cells. This cellular
      diversity ruled out the possibility that Mrgprd(+) neurons innervate a dedicated
      class of SG neuron. Our findings set broad constraints on the types of spinal
      neurons that process afferent input from Mrgprd(+) polymodal nociceptors.

PMID- 19846711
TI  - Single-trial phase precession in the hippocampus.
AB  - During the crossing of the place field of a pyramidal cell in the rat
      hippocampus, the firing phase of the cell decreases with respect to the local
      theta rhythm. This phase precession is usually studied on the basis of data in
      which many place field traversals are pooled together. Here we study properties
      of phase precession in single trials. We found that single-trial and pooled-trial
      phase precession were different with respect to phase-position correlation, phase
      time correlation, and phase range. Whereas pooled-trial phase precession may span
      360 degrees , the most frequent single-trial phase range was only approximately
      180 degrees. In pooled trials, the correlation between phase and position (r = 
      0.58) was stronger than the correlation between phase and time (r = -0.27),
      whereas in single trials these correlations (r = -0.61 for both) were not
      significantly different. Next, we demonstrated that phase precession exhibited a
      large trial-to-trial variability. Overall, only a small fraction of the trial-to
      trial variability in measures of phase precession (e.g., slope or offset) could
      be explained by other single-trial properties (such as running speed or firing
      rate), whereas the larger part of the variability remains to be explained.
      Finally, we found that surrogate single trials, created by randomly drawing
      spikes from the pooled data, are not equivalent to experimental single trials:
      pooling over trials therefore changes basic measures of phase precession. These
      findings indicate that single trials may be better suited for encoding temporally
      structured events than is suggested by the pooled data.

PMID- 19846710
TI  - Endocannabinoid-dependent homeostatic regulation of inhibitory synapses by
      miniature excitatory synaptic activities.
AB  - Homeostatic regulation of synaptic strength in response to persistent changes of
      neuronal activity plays an important role in maintaining the overall level of
      circuit activity within a normal range. Absence of miniature EPSCs (mEPSCs) for a
      few hours is known to cause upregulation of excitatory synaptic strength,
      suggesting that mEPSCs contribute to the maintenance of excitatory synaptic
      functions. In the present study, we found that the absence of mEPSCs for 1-3 h
      also resulted in homeostatic suppression of presynaptic functions of inhibitory
      synapses in acute cortical slices from juvenile rats, as suggested by the reduced
      frequency (but not amplitude) of miniature IPSCs (mIPSCs) as well as the reduced
      amplitude of IPSCs. This homeostatic regulation depended on endocannabinoid (eCB)
      signaling, because blockade of either the activation of cannabinoid type-1
      receptors (CB1Rs) or the synthesis of its endogenous ligand 2
      arachidonoylglycerol (2-AG) abolished the suppression of inhibitory synapses
      caused by the absence of mEPSCs. Blockade of group I metabotropic glutamate
      receptors (mGluR-I) also abolished the suppression of inhibitory synapses,
      consistent with the mGluR-I requirement for eCB synthesis and release in cortical
      synapses. Furthermore, this homeostatic regulation also required eukaryotic
      elongation factor-2 (eEF2)-dependent protein synthesis, but not gene
      transcription. Activation of eEF2 alone was sufficient to suppress the mIPSC
      frequency, an effect abolished by inhibiting CB1Rs. Thus, mEPSCs contribute to
      the maintenance of inhibitory synaptic function and the absence of mEPSCs results
      in presynaptic suppression of inhibitory synapses via protein synthesis-dependent
      elevation of eCB signaling.

PMID- 19846713
TI  - The differential role of motor cortex in stretch reflex modulation induced by
      changes in environmental mechanics and verbal instruction.
AB  - The motor cortex assumes an increasingly important role in higher mammals
      relative to that in lower mammals. This is true to such an extent that the human
      motor cortex is deeply involved in reflex regulation and it is common to speak of
      "transcortical reflex loops." Such loops appear to add flexibility to the human
      stretch reflex, once considered to be immutable, allowing it to adapt across a
      range of functional tasks. However, the purpose of this adaptation remains
      unclear. A common proposal is that stretch reflexes contribute to the regulation
      of limb stability; increased reflex sensitivity during tasks performed in
      unstable environments supports this hypothesis. Alternatively, before movement
      onset, stretch reflexes can assist an imposed stretch, opposite to what would be
      expected from a stabilizing response. Here we show that stretch reflex modulation
      in tasks that require changes in limb stability is mediated by motor cortical
      pathways, and that these differ from pathways contributing to reflex modulation
      that depend on how the subject is instructed to react to an imposed perturbation.
      By timing muscle stretches such that the modulated portion of the reflex occurred
      within a cortical silent period induced by transcranial magnetic stimulation, we
      abolished the increase in reflex sensitivity observed when individuals stabilized
      arm posture within a compliant environment. Conversely, reflex modulation caused
      by altered task instruction was unaffected by cortical silence. These results
      demonstrate that task-dependent changes in reflex function can be mediated
      through multiple neural pathways and that these pathways have task-specific
      roles.

PMID- 19846712
TI  - Disruption of the axon initial segment cytoskeleton is a new mechanism for
      neuronal injury.
AB  - Many factors contribute to nervous system dysfunction and failure to regenerate
      after injury or disease. Here, we describe a previously unrecognized mechanism
      for nervous system injury. We show that neuronal injury causes rapid,
      irreversible, and preferential proteolysis of the axon initial segment (AIS)
      cytoskeleton independently of cell death or axon degeneration, leading to loss of
      both ion channel clusters and neuronal polarity. Furthermore, we show this is
      caused by proteolysis of the AIS cytoskeletal proteins ankyrinG and betaIV
      spectrin by the calcium-dependent cysteine protease calpain. Importantly, calpain
      inhibition is sufficient to preserve the molecular organization of the AIS both
      in vitro and in vivo. We conclude that loss of AIS ion channel clusters and
      neuronal polarity are important contributors to neuronal dysfunction after
      injury, and that strategies to facilitate recovery must preserve or repair the
      AIS cytoskeleton.

PMID- 19846714
TI  - Protein kinase C mediates the synergistic interaction between agonists acting at
      alpha2-adrenergic and delta-opioid receptors in spinal cord.
AB  - Coactivation of spinal alpha(2)-adrenergic receptors (ARs) and opioid receptors
      produces antinociceptive synergy. Antinociceptive synergy between intrathecally
      administered alpha(2)AR and opioid agonists is well documented, but the mechanism
      underlying this synergy remains unclear. The delta-opioid receptor (DOP) and the
      alpha(2A)ARs are coexpressed on the terminals of primary afferent fibers in the
      spinal cord where they may mediate this phenomenon. We evaluated the ability of
      the DOP-selective agonist deltorphin II (DELT), the alpha(2)AR agonist clonidine
      (CLON) or their combination to inhibit calcitonin gene-related peptide (CGRP)
      release from spinal cord slices. We then examined the possible underlying
      signaling mechanisms involved through coadministration of inhibitors of
      phospholipase C (PLC), protein kinase C (PKC) or protein kinase A (PKA).
      Potassium-evoked depolarization of spinal cord slices caused concentration
      dependent release of CGRP. Coadministration of DELT and CLON inhibited the
      release of CGRP in a synergistic manner as confirmed statistically by
      isobolograpic analysis. Synergy was dependent on the activation of PLC and PKC,
      but not PKA, whereas the effect of agonist administration alone was only
      dependent on PLC. The importance of these findings was confirmed in vivo, using a
      thermal nociceptive test, demonstrating the PKC dependence of CLON-DELT
      antinociceptive synergy in mice. That inhibition of CGRP release by the
      combination was maintained in the presence of tetrodotoxin in spinal cord slices
      suggests that synergy does not rely on interneuronal signaling and may occur
      within single subcellular compartments. The present study reveals a novel
      signaling pathway underlying the synergistic analgesic interaction between DOP
      and alpha(2)AR agonists in the spinal cord.

PMID- 19846716
TI  - Nitric oxide potentiation of locomotor activity in the spinal cord of the
      lamprey.
AB  - To understand the intrinsic operation of spinal networks generating locomotion,
      we need to not only characterize the constituent neurons and their connectivity,
      but also determine the role of intrinsic modulation in shaping the final motor
      output. We have focused on the effects of nitric oxide (NO) on the locomotor
      frequency and the underlying synaptic mechanisms in the lamprey spinal cord. To
      identify the source of NO, we used NADPH-diaphorase histochemistry and nNOS
      immunocytochemistry. Gray matter and sensory neurons were positively labeled
      using both methods. Preparations preincubated with NO synthase inhibitors
      displayed slower locomotor frequency that increased upon washout of the
      inhibitors, suggesting that NO is an endogenous neuromodulator in the spinal
      cord. Application of NO donors increased the locomotor frequency that was blocked
      by an NO scavenger and partially reduced by an inhibitor of sGC. To analyze the
      synaptic modulation underlying the NO-induced increase of the locomotor frequency
      we performed intracellular recordings from motoneurons and interneurons. The NO
      induced increase in locomotor frequency was associated with a decrease in the
      midcycle inhibition and an increase in on-cycle excitation. To determine the site
      of action of NO, we examined the effect of NO donors on miniature PSCs. NO
      increased both the frequency and amplitude of mEPSCs while it only decreased the
      frequency of mIPSCs, suggesting the increased excitation is mediated by both
      presynaptic and postsynaptic mechanisms, while the decrease in inhibition
      involves only presynaptic mechanisms. Our results demonstrate a significant role
      of NO in adult vertebrate motor control which, via modulation of both excitatory
      and inhibitory transmission, increases the locomotor burst frequency.

PMID- 19846715
TI  - Prostaglandin E2-induced masculinization of brain and behavior requires protein
      kinase A, AMPA/kainate, and metabotropic glutamate receptor signaling.
AB  - Prostaglandin E(2) (PGE(2)) mediates the masculinization of adult sex behavior in
      rats in response to the surge in serum testosterone at approximately birth.
      Measures of behavioral masculinization correlate with a twofold increase in
      spinophilin protein and the density of dendritic spines in the medial preoptic
      area (POA). Of the four receptors for PGE(2), EP(2) and EP(4) are required for
      the masculinization of behavior by PGE(2). EP(2) and EP(4) couple to G(s)
      proteins, activating protein kinase A (PKA). By using H89 (N-[2-(p-bromo
      cinnamylamino)-ethyl]-5-isoquinoline-sulfon-amide 2HCl) and Ht31, disruptors of
      PKA signaling, we have determined that PKA signaling is required for the
      masculinization of behavior by PGE(2). Glutamatergic signaling often mediates
      PGE(2) signaling; therefore, we tested whether inhibition of AMPA/kainate and
      metabotropic glutamate receptor (mGluR) signaling prevents PGE(2)-induced
      behavioral masculinization and whether activation of glutamate receptors mimics
      PGE(2). Females treated neonatally with NBQX (2,3-dihydroxy-6-nitro-7-sulfonyl
      benzo[f]quinoxaline) plus LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1
      yl]-3-(xanth-9-yl) propanoic acid] combined (AMPA/kainate and mGluR inhibitors,
      respectively) before PGE(2) did not exhibit as many mounts or intromission-like
      behaviors or initiate these behaviors as quickly as animals treated with PGE(2)
      alone. Animals neonatally treated with kainate, (+/-)-1-amino-1,3
      cyclopentanedicarboxylic acid (ACPD) (type I mGluR agonist), or the two combined
      mounted as frequently and initiated mounting behavior as quickly as those given
      PGE(2). Ht31 does not prevent the masculinization of behavior by ACPD plus
      kainate cotreatment; rather, the coadministration of NBQX plus LY341495 prevents
      the forskolin-induced formation of POA dendritic spine-like processes. We
      conclude that PKA, AMPA/kainate, and metabotropic glutamate receptor signaling
      are necessary for the effects of PGE(2), that each receptor individually suffices
      to organize behavior, and that PKA is upstream of the glutamate receptors.

PMID- 19846718
TI  - Predicting the unpredictable: weighted averaging of past stimulus timing
      facilitates ocular pursuit of randomly timed stimuli.
AB  - In motor control, prediction of future events is vital for overcoming sensory
      motor processing delays and facilitating rapid and accurate responses in a
      dynamic environment. In human ocular pursuit this is so pervasive that prediction
      of future target motion cannot easily be eliminated by randomizing stimulus
      parameters. We investigated the prediction of temporally randomized events during
      pursuit of alternating constant-velocity (ramp) stimuli in which the timing of
      direction changes varied unpredictably over a given range. Responses were not
      reactive; instead, smooth eye velocity began to decelerate in anticipation of
      each target reversal. In the first experiment, using a continuous-motion
      stimulus, we found that the time at which this occurred was relatively constant
      regardless of ramp duration, but increased as mean ramp duration of the range
      increased. Regression analysis revealed a quantitative association between
      deceleration timing and the previous two or three ramp durations in a trial,
      suggesting that recent stimulus history was used to create a running average of
      anticipatory timing. In the second experiment, we used discrete motion stimuli,
      with intervening periods of fixation, which allowed both target velocity and
      reversal timing to be varied, thereby decoupling ramp duration and displacement.
      This enabled us to confirm that the timing of anticipatory deceleration was based
      on the history of timing, rather than displacement, within the stimulus. We
      conclude that this strategy is used to minimize error amid temporal uncertainty,
      while simultaneously overcoming inherent delays in visuomotor processing.

PMID- 19846717
TI  - The TC10-Exo70 complex is essential for membrane expansion and axonal
      specification in developing neurons.
AB  - Axonal elongation is one of the hallmarks of neuronal polarization. This
      phenomenon requires axonal membrane growth by exocytosis of plasmalemmal
      precursor vesicles (PPVs) at the nerve growth cone, a process regulated by IGF-1
      activation of the PI3K (phosphatidylinositol-3 kinase) pathway. Few details are
      known, however, about the targeting mechanisms for PPVs. Here, we show, in
      cultured hippocampal pyramidal neurons and growth cones isolated from fetal rat
      brain, that IGF-1 activates the GTP-binding protein TC10, which triggers
      translocation to the plasma membrane of the exocyst component exo70 in the distal
      axon and growth cone. We also show that TC10 and exo70 function are necessary for
      addition of new membrane and, thus, axon elongation stimulated by IGF-1.
      Moreover, expression silencing of either TC10 or exo70 inhibit the establishment
      of neuronal polarity by hindering the insertion of IGF-1 receptor in one of the
      undifferentiated neurites. We conclude that, in hippocampal pyramidal neurons in
      culture, (1) membrane expansion at the axonal growth cone is regulated by IGF-1
      via a cascade involving TC10 and the exocyst complex, (2) TC10 and exo70 are
      essential for the polarized externalization of IGF-1 receptor, and (3) this
      process is necessary for axon specification.

PMID- 19846719
TI  - F-BAR proteins of the syndapin family shape the plasma membrane and are crucial
      for neuromorphogenesis.
AB  - Coordinated functions of the actin cytoskeleton and microtubules, which require
      careful control in time and space, are indispensable for the drastic alterations
      of neuronal morphology during neuromorphogenesis and neuronal network formation.
      Actin filament formation driven by the Arp2/3 complex and its activator neural
      Wiskott-Aldrich syndrome protein (N-WASP) is important for proper axon
      development. The underlying molecular mechanisms for targeting to and specific
      activation of N-WASP at the neuronal plasma membrane, however, have thus far
      remained elusive. We show that syndapin I is critical for proper
      neuromorphogenesis and hereby uses N-WASP as a cytoskeletal effector. Upon N-WASP
      binding, syndapins release N-WASP autoinhibition. Syndapins hereby cooperate with
      Cdc42 and phosphatidyl-inositol-(4,5)-bisphosphate. Syndapins furthermore
      specifically bind to phosphatidylserine-containing membranes via their extended F
      BAR domain. Dissecting the syndapin functions actin nucleation and direct
      membrane binding in vivo, we demonstrate that both functions are physiologically
      relevant and required. Constitutive plasma membrane-targeting experiments in vivo
      indicate that specifically actin nucleation at the cell cortex is triggered by
      syndapins. Consistent with syndapins steering N-WASP as downstream effector for
      cortical actin nucleation, syndapin-induced neuronal arborization is N-WASP and
      Cdc42 dependent. The functions of syndapin-N-WASP complexes in neuromorphogenesis
      were revealed by loss-of-function studies. Knockdown of syndapin I leads to
      impaired axon development and especially phenocopies the aberrant axon branching
      observed upon N-WASP and Arp2/3 complex deficiency. In contrast, proper length
      control involves another N-WASP-binding protein, Abp1. Our data thus reveal that
      syndapin I is crucial for neuromorphogenesis and that different N-WASP activators
      ensure fine control of N-WASP activity and have distinct functions during
      neuronal network formation.

PMID- 19846720
TI  - In vivo role of a potassium channel-binding protein in regulating neuronal
      excitability and behavior.
AB  - Molecular details of ion channel interactions with modulatory subunits have been
      investigated widely in transfected cells, but the physiological roles of ion
      channel modulatory protein complexes in native neurons remain largely unexplored.
      The Drosophila large-conductance calcium-activated potassium channel (dSlo) binds
      to and is modulated by its binding partner Slob. We have constructed flies in
      which Slob expression is manipulated by P-element mutagenesis, or by transgenic
      expression of Slob protein or Slob-RNAi. In vivo recordings of both macroscopic
      and single dSlo channel currents in identified neurosecretory neurons in the pars
      intercerebralis (PI) region of the Drosophila brain reveal that whole-cell
      potassium current and properties of single dSlo channels are modulated by Slob
      expression level. Furthermore, Slob genotype influences action potential duration
      in vivo. This unprecedented combination of current-clamp, macroscopic-current,
      and single-channel recordings from neurons in brains of living flies defines a
      critical role for an ion channel modulatory protein complex in the control of
      neuronal excitability. We show further that Slob-null flies exhibit significantly
      longer lifespan than controls under conditions of complete food deprivation.
      Crosses with deficiency lines demonstrate that this enhanced resistance to
      starvation-induced death maps close to the slob locus. Together, these results
      indicate that Slob may serve a novel regulatory function in feeding behavior,
      possibly by influencing the excitability of the PI neurons.

PMID- 19846721
TI  - Task-dependent activations of human auditory cortex during pitch discrimination
      and pitch memory tasks.
AB  - The functional organization of auditory cortex (AC) is still poorly understood.
      Previous studies suggest segregation of auditory processing streams for spatial
      and nonspatial information located in the posterior and anterior AC, respectively
      (Rauschecker and Tian, 2000; Arnott et al., 2004; Lomber and Malhotra, 2008).
      Furthermore, previous studies have shown that active listening tasks strongly
      modulate AC activations (Petkov et al., 2004; Fritz et al., 2005; Polley et al.,
      2006). However, the task dependence of AC activations has not been systematically
      investigated. In the present study, we applied high-resolution functional
      magnetic resonance imaging of the AC and adjacent areas to compare activations
      during pitch discrimination and n-back pitch memory tasks that were varied
      parametrically in difficulty. We found that anterior AC activations were
      increased during discrimination but not during memory tasks, while activations in
      the inferior parietal lobule posterior to the AC were enhanced during memory
      tasks but not during discrimination. We also found that wide areas of the
      anterior AC and anterior insula were strongly deactivated during the pitch memory
      tasks. While these results are consistent with the proposition that the anterior
      and posterior AC belong to functionally separate auditory processing streams, our
      results show that this division is present also between tasks using spatially
      invariant sounds. Together, our results indicate that activations of human AC are
      strongly dependent on the characteristics of the behavioral task.

PMID- 19846722
TI  - The time course of dopamine transmission in the ventral tegmental area.
AB  - Synaptic transmission mediated by G-protein coupled receptors (GPCR) is not
      generally thought to be point-to-point. To determine the extent over which
      dopamine signals in the midbrain, the present study examined the concentration
      and time course of dopamine that underlies a D(2)-receptor IPSC (D(2)-IPSC) in
      the ventral tegmental area. Extracellular dopamine was measured electrochemically
      while simultaneously recording D(2)-IPSCs. The presence of dopamine was brief
      relative to the IPSC, suggesting that G-protein dependent potassium channel
      activation determined the IPSC time course. The activation kinetics of D(2)
      receptor-dependent potassium current was studied using outside-out patch
      recordings with rapid application of dopamine. Dopamine applied at a minimum
      concentration of 10 mum for a maximum of 100 ms mimicked the IPSC. Higher
      concentrations applied for as little as 5 ms did not change the kinetics of the
      current. The results indicate that both the intrinsic kinetics of G-protein
      coupled receptor signaling and a rapidly rising high concentration of dopamine
      determine the time course of the IPSC. Thus, dopamine transmission in the
      midbrain is more localized then previously proposed.

PMID- 19846723
TI  - Kv7/KCNQ channels control action potential phasing of pyramidal neurons during
      hippocampal gamma oscillations in vitro.
AB  - While the synaptic mechanisms involved in the generation of in vitro network
      oscillations have been widely studied, little is known about the importance of
      voltage-gated currents during such activity. Here we study the role of the M
      current (I(M)) in the modulation of network oscillations in the gamma-frequency
      range (20-80 Hz). Kv7/KCNQ subunits, the molecular correlates of I(M), are
      abundantly expressed in CA1 and CA3 pyramidal neurons, and I(M) is an important
      modulator of pyramidal neuron firing. Using hippocampal slices, we recorded field
      activity and pyramidal neuron action potential timing during kainate-induced
      gamma oscillations. Application of the specific I(M) blocker XE991 causes a
      significant reduction of gamma oscillation amplitude with no significant change
      in oscillation frequency. Concomitant CA3 pyramidal neuron recordings show a
      significant increase in action potential frequency during ongoing gamma
      oscillations after the application of XE991. This increase is associated with a
      significant loss of periodicity of pyramidal neuron action potentials relative to
      the phase of the gamma oscillations. Using dynamic clamp, we show that I(M) acts
      to improve the periodicity of action potential timing and to decrease action
      potential frequency. We further validate these results in a compartmental model
      of a pyramidal neuron. Our work suggests that I(M) modulates gamma oscillations
      by regulating the phasing of action potential firing in pyramidal neurons.

PMID- 19846724
TI  - Ventral striatal neurons encode the value of the chosen action in rats deciding
      between differently delayed or sized rewards.
AB  - The ventral striatum (VS) is thought to serve as a gateway whereby associative
      information from the amygdala and prefrontal regions can influence motor output
      to guide behavior. If VS mediates this "limbic-motor" interface, then one might
      expect neural correlates in VS to reflect this information. Specifically, neural
      activity should reflect the integration of motivational value with subsequent
      behavior. To test this prediction, we recorded from single units in VS while rats
      performed a choice task in which different odor cues indicated that reward was
      available on the left or on the right. The value of reward associated with a left
      or rightward movement was manipulated in separate blocks of trials by either
      varying the delay preceding reward delivery or by changing reward size. Rats'
      behavior was influenced by the value of the expected reward and the response
      required to obtain it, and activity in the majority of cue-responsive VS neurons
      reflected the integration of these two variables. Unlike similar cue-evoked
      activity reported previously in dopamine neurons, these correlates were only
      observed if the directional response was subsequently executed. Furthermore,
      activity was correlated with the speed at which the rats' executed the response.
      These results are consistent with the notion that VS serves to integrate
      information about the value of an expected reward with motor output during
      decision making.

PMID- 19846725
TI  - Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in
      nociceptive processing.
AB  - Peripheral tissue injury is associated with changes in protein expression in
      sensory neurons that may contribute to abnormal nociceptive processing. We used
      cultured dorsal root ganglion (DRG) neurons as a model of axotomized neurons to
      investigate early changes in protein expression after nerve injury. Comparing
      protein levels immediately after DRG dissociation and 24 h later by proteomic
      differential expression analysis, we found a substantial increase in the levels
      of the neurotrophin-inducible protein VGF (nonacronymic), a putative neuropeptide
      precursor. In a rodent model of nerve injury, VGF levels were increased within 24
      h in both injured and uninjured DRG neurons, and the increase persisted for at
      least 7 d. VGF was also upregulated 24 h after hindpaw inflammation. To determine
      whether peptides derived from proteolytic processing of VGF participate in
      nociceptive signaling, we examined the spinal effects of AQEE-30 and LQEQ-19,
      potential proteolytic products shown previously to be bioactive. Each peptide
      evoked dose-dependent thermal hyperalgesia that required activation of the
      mitogen-activated protein kinase p38. In addition, LQEQ-19 induced p38
      phosphorylation in spinal microglia when injected intrathecally and in the BV-2
      microglial cell line when applied in vitro. In summary, our results demonstrate
      rapid upregulation of VGF in sensory neurons after nerve injury and inflammation
      and activation of microglial p38 by VGF peptides. Therefore, VGF peptides
      released from sensory neurons may participate in activation of spinal microglia
      after peripheral tissue injury.

PMID- 19846726
TI  - The development of the thalamic motor learning area is regulated by Fgf8
      expression.
AB  - Habenular nuclei play a key role in the control of motor and cognitive behavior,
      processing emotion, motivation, and reward values in the brain. Thus, analysis of
      the molecular and cellular mechanisms underlying the development and evolution of
      this region will contribute to a better understanding of brain function. The Fgf8
      gene is expressed in the dorsal midline of the diencephalon, close to the area in
      which the habenular region will develop. Given that Fgf8 is an important
      morphogenetic signal, we decided to investigate the role of Fgf8 signaling in
      diencephalic development. To this end, we analyzed the effects of altered Fgf8
      expression in the mouse embryo, using molecular and cellular markers. Decreasing
      Fgf8 activity in the diencephalon was found to be associated with dosage
      dependent alterations in the epithalamus: the habenular region and pineal gland
      are reduced or lacking in Fgf8 hypomorphic mice. Actually, our findings indicate
      that Fgf8 may be the master gene for these diencephalic domains, acting as an
      inductive and morphogenetic regulator. Therefore, the emergence of the habenular
      region in vertebrates could be understood in terms of a phylogenetic territorial
      addition caused by de novo expression of Fgf8 in the diencephalic alar plate.
      This region specializes to permit the development of adaptive control of the
      motor function in the vertebrate brain.

PMID- 19846727
TI  - Evidence against AMPA receptor-lacking glutamatergic synapses in the superficial
      dorsal horn of the rat spinal cord.
AB  - Pure NMDA receptor (NMDAr)-mediated EPSCs, thought to correspond to "silent"
      glutamatergic synapses that lack AMPA receptors (AMPArs), have been observed in
      superficial spinal dorsal horn of neonatal but not adult rats. Recent anatomical
      studies suggest that AMPArs are present at virtually all glutamatergic synapses
      in this region in adults. We used antigen retrieval to examine colocalization of
      AMPArs and PSD-95 (a marker for glutamatergic synapses) in laminae I-II of
      neonatal and adult rats. We found a high degree of colocalization in all cases,
      which suggests that AMPArs are present in the great majority of glutamatergic
      synapses even in neonatal animals. We therefore reexamined evidence for silent
      synapses by performing blind whole-cell recordings from superficial dorsal horn
      neurons in slices from neonatal or adult rats, with focal stimulation to activate
      glutamatergic synapses. On some occasions in both neonatal (10 of 109, 9%) and
      adult (9 of 77, 12%) slices, NMDAr-mediated EPSCs were observed when the holding
      potential was raised to +50 mV at a stimulus strength that had failed to evoke
      AMPAr-mediated EPSCs. However, in all cases tested, AMPAr-mediated EPSCs were
      then observed when the cell was returned to -70 mV; this and other properties of
      the EPSCs suggest that they do not represent genuine silent synapses. When
      compared with previous findings, our results indicate that the appearance of
      silent synapses depends on experimental protocol. This suggests that pure NMDAr
      mediated EPSCs seen in previous studies do not correspond to AMPAr-lacking
      synapses but result from another mechanism, for example, loss of labile AMPArs
      from recently formed synapses.

PMID- 19846728
TI  - Distributed and antagonistic contributions of ongoing activity fluctuations to
      auditory stimulus detection.
AB  - Recent studies have shown that ongoing activity fluctuations influence trial-by
      trial perception of identical stimuli. Some brain systems seem to bias toward
      better perceptual performance and others toward worse. We tested whether these
      observations generalize to another as of yet unassessed sensory modality,
      audition, and a nonspatial but memory-dependent paradigm. In a sparse event
      related functional magnetic resonance imaging design, we investigated detection
      of auditory near-threshold stimuli as a function of prestimulus baseline activity
      in early auditory cortex as well as several distributed networks that were
      defined on the basis of resting state functional connectivity. In accord with
      previous studies, hits were associated with higher prestimulus activity in
      related early sensory cortex as well as in a system comprising anterior insula,
      anterior cingulate, and thalamus, which other studies have related to processing
      salience and maintaining task set. In contrast to previous studies, however,
      higher prestimulus activity in the so-called dorsal attention system of frontal
      and parietal cortex biased toward misses, whereas higher activity in the so
      called default mode network that includes posterior cingulate and precuneus
      biased toward hits. These results contradict a simple dichotomic view on the
      function of these two latter brain systems where higher ongoing activity in the
      dorsal attention network would facilitate perceptual performance, and higher
      activity in the default mode network would deteriorate perceptual performance.
      Instead, we show that the way in which ongoing activity fluctuations impact on
      perception depends on the specific sensory (i.e., nonspatial) and cognitive
      (i.e., mnemonic) context that is relevant.

PMID- 19846729
TI  - Mental training enhances attentional stability: neural and behavioral evidence.
AB  - The capacity to stabilize the content of attention over time varies among
      individuals, and its impairment is a hallmark of several mental illnesses.
      Impairments in sustained attention in patients with attention disorders have been
      associated with increased trial-to-trial variability in reaction time and event
      related potential deficits during attention tasks. At present, it is unclear
      whether the ability to sustain attention and its underlying brain circuitry are
      transformable through training. Here, we show, with dichotic listening task
      performance and electroencephalography, that training attention, as cultivated by
      meditation, can improve the ability to sustain attention. Three months of
      intensive meditation training reduced variability in attentional processing of
      target tones, as indicated by both enhanced theta-band phase consistency of
      oscillatory neural responses over anterior brain areas and reduced reaction time
      variability. Furthermore, those individuals who showed the greatest increase in
      neural response consistency showed the largest decrease in behavioral response
      variability. Notably, we also observed reduced variability in neural processing,
      in particular in low-frequency bands, regardless of whether the deviant tone was
      attended or unattended. Focused attention meditation may thus affect both
      distracter and target processing, perhaps by enhancing entrainment of neuronal
      oscillations to sensory input rhythms, a mechanism important for controlling the
      content of attention. These novel findings highlight the mechanisms underlying
      focused attention meditation and support the notion that mental training can
      significantly affect attention and brain function.

PMID- 19846730
TI  - Left ventricular diastolic function in type 2 diabetes mellitus: prevalence and
      association with myocardial and vascular disease.
AB  - BACKGROUND: Although type 2 diabetes mellitus is a risk factor for developing
      congestive heart failure, the mechanism leading to heart failure is unclear. We
      examined the prevalence of left ventricular (LV) systolic and diastolic
      dysfunction in patients with type 2 diabetes mellitus in relation to vascular
      function and myocardial perfusion. METHODS AND RESULTS: A prospective
      observational study of 305 patients with type 2 diabetes mellitus (diabetes
      duration, 4.5+/-5.3 years) referred consecutively to a diabetes clinic were
      screened for LV systolic and diastolic function by echocardiography. Vascular
      function was estimated using noninvasive estimation of pulse pressure, carotid
      arterial compliance, total arterial compliance, and valvulo-arterial impedance.
      The prevalences of LV diastolic dysfunction and left atrial (LA) volume index >32
      mL/m(2) were 40% and 32%, respectively. The prevalence of myocardial ischemia on
      myocardial perfusion scintigraphy was more frequent in patients with grade 2
      diastolic dysfunction and LA volume index >32 mL/m(2) compared with those having
      normal or grade 1 diastolic dysfunction (P=0.002) or LA volume index < or =32
      mL/m(2) (P<0.001), respectively. Predictors of grade 2 diastolic dysfunction and
      LA dilation were summed stress score on myocardial perfusion scintigraphy, total
      arterial compliance, and valvulo-arterial impedance, whereas pulse pressure and
      carotid arterial compliance were not, after adjusting for age, sex, and diabetes
      duration. On multivariable modeling, summed stress score (P<0.001) and valvulo
      arterial impedance (P=0.027) remained predictors of grade 2 diastolic
      dysfunction, and only summed stress score (P<0.001) was a predictor of LA
      dilation. CONCLUSIONS: Abnormal LV filling is closely associated with abnormal
      myocardial perfusion on myocardial perfusion scintigraphy, whereas the
      association of LV filling with vascular function is less prominent.

PMID- 19846731
TI  - Mitochondrial function and insulin resistance in overweight and normal-weight
      children.
AB  - BACKGROUND: Obesity has become an epidemic in children, associated with an
      increase in insulin resistance and metabolic dysfunction. Mitochondrial function
      is known to be an important determinant of glucose metabolism in adults. However,
      little is known about the relationship between mitochondrial function and
      obesity, insulin resistance, energy expenditure, and pubertal development in
      children. METHODS: Seventy-four participants, 37 overweight (> or = 85th
      percentile body mass index for age and sex) and 37 normal-weight (< 85th
      percentile) without personal or family history of diabetes mellitus were
      enrolled. Subjects were evaluated with an oral glucose tolerance test, metabolic
      markers, resting energy expenditure, Tanner staging, and (31)P magnetic resonance
      spectroscopy of skeletal muscle for mitochondrial function. RESULTS: Overweight
      and normal-weight children showed no difference in muscle ATP synthesis
      [phosphocreatine (PCr) recovery after exercise] (32.4 +/- 2.3 vs. 34.1 +/- 2.1, P
      = 0.58). However, insulin-resistant children had significantly prolonged PCr
      recovery when compared with insulin-sensitive children, by homeostasis model
      assessment for insulin resistance quartile (ANOVA, P = 0.04). Similarly, insulin
      resistant overweight children had PCr recovery that was prolonged compared with
      insulin-sensitive overweight children (P = 0.01). PCr recovery was negatively
      correlated with resting energy expenditure in multivariate modeling (P = 0.03).
      Mitochondrial function worsened during mid-puberty in association with insulin
      resistance. CONCLUSION: Reduced skeletal muscle mitochondrial oxidative
      phosphorylation, assessed by PCr recovery, is associated with insulin resistance
      and an altered metabolic phenotype in children. Normal mitochondrial function may
      be associated with a healthier metabolic phenotype in overweight children.
      Further studies are needed to investigate the long-term physiological
      consequences and potential treatment strategies targeting children with reduced
      mitochondrial function.

PMID- 19846732
TI  - A prospective study of abdominal obesity and coronary artery calcium progression
      in older adults.
AB  - OBJECTIVE: Little is known about obesity measurements and coronary artery calcium
      (CAC) progression in older adults. We examined the sex-specific association
      between measures of body size and fat distribution with CAC progression. SUBJECTS
      AND METHODS: Participants were 156 men and 182 women (mean age 67 yr) without
      known heart disease who had electron-beam computed tomography for CAC at baseline
      and again 4.5 yr later. Obesity assessments were weight, height, body mass index,
      waist and hip circumference, waist to hip ratio, waist to height ratio, sc and
      visceral adipose tissue (SAT, VAT), and SAT to VAT ratio based on abdominal
      electron-beam computed tomography. CAC progression was defined as categorical
      (square root increased on total CAC volume score > or = 2.5 mm(3)) and continuous
      variables. RESULTS: During the follow-up, 55% of men and 38.5% of women had CAC
      progression. Increased waist to hip ratio (> or = 0.9 for men, > or = 0.85 for
      women) and waist to height ratio (> or = 0.55 for men, > or = 0.54 for women)
      were positively and independently associated with CAC progression [median
      (interquartile range)] [60.8 (145) vs. 10.8 (56) mm(3), P = 0.002 and 50 (153)
      vs. 22(84) mm(3), P = 0.03, respectively]. In women but not men, an increased
      waist circumference (> 88 cm) independently predicted CAC progression (odds ratio
      3.0 95% confidence interval 1.03-8.0, P = 0.04), whereas VAT to SAT ratio
      predicted CAC progression in men but not women (odds ratio 2.8 95% confidence
      interval 1.01-7.8, P = 0.04). CONCLUSION: In this study of older adults without
      known heart disease, abdominal obesity was an independent predictor of CAC
      progression. These results point to the importance of using clinical measurements
      of abdominal obesity to identify individuals at increased risk for
      atherosclerosis.

PMID- 19846733
TI  - Serum insulin-like growth factor-I concentration is associated with leukocyte
      telomere length in a population-based cohort of elderly men.
AB  - CONTEXT: Both leukocyte telomere length and IGF-I are associated with the aging
      process. A previous in vitro study suggested that IGF-I may modulate telomerase
      activity in white blood cells, but little is known whether these two systems
      interact in vivo. PATIENTS AND METHODS: Leukocyte telomere length was determined
      using a quantitative PCR assay in 2744 elderly men (mean age 75.5 yr, range 69-81
      yr) included in the population-based Osteoporotic Fractures in Men-Sweden study.
      Serum IGF-I concentration was measured using RIA. RESULTS: Subjects with a
      leukocyte telomere length in the lowest tertile group had lower serum IGF-I
      concentration than subjects in the two tertile groups with longer telomere
      lengths (P = 0.005). Logistic regression analyses showed that a higher serum IGF
      I concentration was associated with a significantly reduced risk of having a
      leukocyte telomere length in the lowest tertile group and also after adjustment
      for multiple covariates (P < 0.01). Multivariate linear regression analyses
      demonstrated that tertile of leukocyte telomere length was positively, whereas
      age was negatively, associated with serum IGF-I concentration in elderly men.
      CONCLUSIONS: In this large population-based, cross-sectional study, leukocyte
      telomere length was positively associated with serum IGF-I concentration in
      elderly men. The mechanisms underlying the association between serum IGF-I
      concentration and leukocyte telomere length remain to be determined.

PMID- 19846734
TI  - Comparison of combined bupropion and naltrexone therapy for obesity with
      monotherapy and placebo.
AB  - CONTEXT: The efficacy of current centrally acting obesity pharmacotherapies is
      limited by compensatory mechanisms that mitigate weight loss. OBJECTIVE: Our
      objective was to determine whether opioid receptor antagonism (naltrexone) plus
      pro-opiomelanocortin activation (bupropion) causes greater weight loss than
      placebo or monotherapy. DESIGN/SETTING: A randomized, placebo- and monotherapy
      controlled, double-blind, dose-finding trial was conducted from August 2005 to
      December 2006 in seven U.S. outpatient clinics. PARTICIPANTS: A total of 419
      patients with uncomplicated obesity participated. INTERVENTIONS: Interventions
      included 24 wk of sustained-release bupropion (400 mg/d), immediate-release
      naltrexone (48 mg/d), placebo, and three combination therapy
      [naltrexone/bupropion (NB)] groups consisting of immediate-release naltrexone,
      16, 32, or 48 mg/d, plus sustained-release bupropion (400 mg/d) with a 24-wk
      extension. A minimal diet and exercise component was also included. MAIN OUTCOME
      MEASURES: Percent weight change from baseline at wk 24 in the intent-to-treat
      population for NB48 vs. placebo and monotherapy was assessed. Other measurements
      included body mass index, waist circumference, fasting lipids, glycemic
      variables, safety, and tolerability. RESULTS: At wk 24, placebo-subtracted weight
      loss was -4.62% [95% confidence interval (CI) -6.24 to -2.99; P < 0.001] for
      NB16, -4.65% (95% CI -6.20 to -3.09; P < 0.001) for NB32, and -3.53% (95% CI 
      5.15 to -1.90; P < 0.001) for NB48. Weight loss was statistically significant vs.
      monotherapy for all three NB combinations with the exception of NB48 vs.
      bupropion. Weight loss with NB continued after wk 24. The most common treatment
      emergent adverse event was mild transient nausea. CONCLUSIONS: NB caused gradual
      sustained weight loss over 48 wk; NB32 and NB16 demonstrated greater weight loss
      in the intent-to-treat population due to lower attrition rates. Further study is
      needed to demonstrate long-term efficacy and safety of NB.

PMID- 19846735
TI  - Prenatal determinants of uterine volume and ovarian reserve in adolescence.
AB  - CONTEXT: Adequate uterine volume and ovarian reserve are essential for
      reproductive health. Antenatal events such as restricted fetal growth and
      maternal tobacco smoking are hypothesized to impact on reproductive function in
      later life, although not studied in a large prospective normal pregnancy
      population to date. OBJECTIVE: The objective of the study was to determine the
      relationship between intrauterine growth, birth weight, and maternal tobacco
      smoking on uterine volume and ovarian reserve in adolescence. DESIGN AND SETTING:
      This was a prospective study in which half the cohort underwent intensive
      ultrasound monitoring in utero. PARTICIPANTS: Intrauterine growth was measured
      using ultrasound at 18, 24, 28, and 34/36 wk gestation (n = 115 girls). Maternal
      smoking data were prospectively collected at 18 and 34/36 wk from the whole
      cohort. Uterine (n = 229) and early follicular ovarian volume and antral follicle
      count (n = 225) were measured using transabdominal ultrasound (n = 230). Ovarian
      reserve was estimated using early follicular phase anti-Mullerian hormone,
      inhibin B, and FSH (n = 213). MAIN OUTCOME MEASURES: The relationship between
      maternal tobacco smoking, intrauterine growth trajectories, and markers of
      ovarian reserve and uterine size in adolescence was measured. RESULTS: Linear
      regression showed that daughters of mothers who smoked had a significantly
      smaller uterus compared with nonsmokers (P = 0.019). No significant relationship
      between maternal tobacco smoking and ovarian volume (P = 0.164) or markers of
      ovarian reserve (antral follicle count, plasma FSH, anti-Mullerian hormone, and
      inhibin B) in adolescence was determined. CONCLUSIONS: Our findings indicate that
      maternal smoking, but not variations in fetal growth, may lead to a reduction in
      uterine volume and does not appear to impact ovarian reserve.

PMID- 19846736
TI  - Waist circumference, atherogenic lipoproteins, and vascular smooth muscle
      biomarkers in children.
AB  - OBJECTIVE: Large waist circumference (WC) is associated with cardiovascular
      disease and type 2 diabetes. The present study determined differences in
      lipoprotein particle size and subclass concentration and markers of vascular
      smooth muscle function in children using WC percentile cutoffs. RESEARCH DESIGN
      AND METHODS: Participants were 182 children (87 black, 92 female) aged 8-<18 yr.
      Each participant had a measurement of WC and a fasting blood draw for the
      measurement of lipoprotein particle concentration and size and circulating
      biomarkers of endothelial function. Participants were divided into age-, sex-,
      and ethnicity-specific WC percentiles of below 75th, 75th to 90th, and at least
      90th percentiles, and differences in lipoproteins and vascular smooth muscle
      markers were compared among groups. RESULTS: Children in the 90th percentile or
      higher for WC had significantly smaller low-density lipoprotein and high-density
      lipoprotein size than children with WC below this percentile. For lipoprotein
      concentration, small low-density lipoprotein and large very low density
      lipoprotein and chylomicrons were lower, and large high density lipoprotein
      concentrations were higher in children whose WC was below the 75th percentile
      compared with those with WC in the 90th percentile or higher. Concentrations of
      the vascular smooth muscle biomarkers, intercellular adhesion molecule-1, and E
      selectin were significantly higher in children with WC in the 90th percentile or
      higher than in children below the 75th percentile. CONCLUSION: Youths with WC in
      the 90th percentile or higher have an atherogenic lipoprotein profile with
      increased concentrations of biomarkers of vascular smooth muscle dysfunction.
      Given that atherosclerosis begins in childhood, such evidence suggests that these
      children should be targeted for interventions to reduce adiposity at an early
      age.

PMID- 19846737
TI  - Association of serum TSH with high body mass differs between smokers and never
      smokers.
AB  - CONTEXT: Recent studies have suggested that the association of low thyroid
      function with high body mass is restricted to nonsmokers. OBJECTIVE: The aim was
      to study the association of thyroid function with body mass separately for
      smokers and never-smokers. DESIGN AND SETTING: We conducted a cross-sectional,
      population-based study. SUBJECTS: We studied 27,097 individuals older than 40 yr
      of age who were without previously known thyroid disease. MAIN OUTCOME MEASURES:
      We measured mean body mass index (BMI) and odds ratio for obesity (BMI > or =
      30.0 kg/m(2)) according to categories of thyroid function, in women and men, and
      separately for current smokers and never-smokers. We also studied the association
      with BMI within the reference range of TSH (0.50-3.5 mU/liter). RESULTS: TSH
      within the reference range was positively associated with BMI (P for trend < or =
      0.001 in all groups) and with the prevalence of obesity (P for trend < 0.005 in
      all groups). Among women, the association did not differ between current smokers
      and never-smokers, but in men the association was stronger for current smokers.
      Hypothyroid function was associated with higher BMI and higher prevalence of
      obesity in women (subclinical and overt hypothyroidism) and men (subclinical
      hypothyroidism), both in current smokers and in never-smokers. CONCLUSION: The
      association of low thyroid function with high body mass was as least as strong in
      current smokers as in never-smokers, and our results clearly show that the
      association is not limited to nonsmokers, as previously suggested.

PMID- 19846738
TI  - Effects of endogenous growth differentiation factor 9 on activin A-induced
      inhibin B production in human granulosa-lutein cells.
AB  - BACKGROUND: We recently reported on the effects of exogenous growth
      differentiation factor 9 (GDF9) in enhancing activin A-induced inhibin beta(B)
      subunit mRNA and inhibin B levels in human granulosa-lutein (hGL) cells by
      modulating key components of the activin signaling pathway. We undertook the
      following study to characterize the role of endogenous GDF9 in this regard.
      METHODS: We compared inhibin subunit (alpha, beta(A), and beta(B)) mRNA and
      inhibin B levels and activation of activin receptors (ACVRs) and Smad signaling
      pathway in hGL cells obtained from women undergoing in vitro fertilization and
      cultured with and without activin A treatment after GDF9-targeting small
      interfering RNA transfection. GDF9, inhibin subunits, ACVR2B/1B and Smad2/3/4/7
      mRNA and/or protein levels, Smad phosphorylation, and inhibin B were assessed
      with RT-PCR, immunoblotting, and ELISA. Data were analyzed by ANOVA followed by
      Tukey's test. RESULTS: GDF9 was detected as mRNA and protein in hGL cells and
      protein in follicular fluid from all 11 patients tested. Reduced endogenous GDF9
      expression after targeting small interfering RNA transfection was associated with
      decreased ACVR2B/1B and Smad2/3/4 but increased inhibitory Smad7 mRNA and protein
      levels and, consequently, reduced activin A-induced beta(B)-subunit mRNA and
      inhibin B levels. CONCLUSIONS: We report here for the first time autocrine roles
      for endogenous GDF9 in hGL cells in enhancing activin A-induced beta(B)-subunit
      mRNA and inhibin B levels via key components of the activin signaling pathway.
      However, the relative contributions of GDF9 in granulosa cells vs. oocyte as
      autocrine/paracrine regulators of beta(B)-subunit and inhibin B production in
      normal and abnormal human ovarian functions remain to be determined.

PMID- 19846739
TI  - The role of insulin-like growth factor (IGF) binding protein-2 in the insulin
      mediated decrease in IGF-I bioactivity.
AB  - CONTEXT: Insulin interacts with the GH-IGF system by a reciprocal regulation of
      IGF-binding proteins (IGFBP) and GH, which in turn regulate insulin sensitivity
      via bioactive IGF-I. This network is linked to metabolic syndrome and
      cardiovascular diseases. OBJECTIVE: We evaluated the effect of glucose and
      insulin on IGFBP-1-4, particularly IGFBP-2, in the regulation of bioactive IGF-I
      and its relation to insulin resistance. SETTING: The study was conducted at an
      endocrinology center. RESEARCH DESIGN AND METHODS: Twenty-four healthy subjects
      (12 men; aged 21-72 yr; body mass index 25.9 +/- 0.9 kg/m(2)) and 19 subjects
      with impaired glucose tolerance (IGT; eight men; aged 26-71 yr; body mass index
      28.9 +/- 1.2 kg/m(2)) were prospectively studied using oral glucose tolerance
      test and hyperinsulinemic euglycemic clamp. RESULTS: During the clamp, insulin
      decreased IGF-I bioactivity in both IGT subjects and controls (-16.2 +/- 2.8 and 
      13.9 +/- 3.3%, respectively; P < 0.01). In addition, insulin increased IGFBP-2
      and GH and decreased IGFBP-1 and -4 but did not alter total IGF-I, IGF-II, or
      IGFBP-3 levels. During the oral glucose tolerance test, GH and IGFBP-1 were
      markedly suppressed. Subjects with IGT showed more pronounced insulin resistance
      and lower GH, IGFBP-1, and IGFBP-2 levels (P < 0.05). In multiple regression
      analysis, IGFBP-2 was an independent predictor of insulin sensitivity (beta =
      0.36, P < 0.05) and IGF-I bioactivity (beta = -0.5, P < 0.05). CONCLUSIONS: Our
      data indicate that insulin acutely decreases IGF-I bioactivity through
      differential modulation of IGFBPs. Furthermore, IGFBP-2 plays a central role in
      the insulin-IGF system cross talk and is closely linked to insulin resistance,
      thereby providing a further explanation for its association with the metabolic
      syndrome.

PMID- 19846740
TI  - Criteria for polycystic ovarian morphology in polycystic ovary syndrome as a
      function of age.
AB  - CONCEPT: Ovaries meeting criteria for polycystic ovary morphology during peak
      reproductive years may no longer meet the criteria with age. OBJECTIVE: Ovarian
      volume and follicle number decrease with age in women with polycystic ovary
      syndrome (PCOS), permitting age-dependent criteria for PCOM. DESIGN AND SETTING:
      We conducted longitudinal (7-15 year interval) and cross-sectional studies to
      examine polycystic ovarian morphology over time at an outpatient clinic and
      pathology laboratory in a tertiary care hospital. PATIENTS: Subjects included
      those with PCOS defined by the National Institutes of Health criteria (n = 11 and
      483 for longitudinal and cross-sectional, respectively) and control women with
      regular menstrual cycles and no hyperandrogenism (n = 15 and 367), age 18-64 yr.
      INTERVENTIONS: Subjects underwent an ovarian ultrasound by a single observer.
      MAIN OUTCOME MEASURES: Ovarian volume and follicle number were measured and
      ultrasound findings confirmed by a pathologist in a subset (n = 9). RESULTS:
      Ovarian volume (15.2 +/- 7.4 vs. 7.1 +/- 3.7 ml; P < 0.01) and follicle number
      (12.8 +/- 3.2 vs. 8.1 +/- 3.9; P < 0.05) decreased longitudinally in PCOS and
      control women (volume 11.6 +/- 4.4 vs. 5.4 +/- 2.2 ml and follicle number 8.3 +/-
      1.9 vs. 6.3 +/- 1.8; both P < 0.005). Using cross-sectional data, log ovarian
      volume and follicle number decreased in both groups, but the decrease in log
      ovarian volume was less pronounced in women with PCOS than in controls (P <
      0.01). A combination of age, log ovarian volume, follicle number, and
      testosterone distinguished PCOS subjects from controls with a receiver operator
      characteristic curve area of 0.90. CONCLUSIONS: Ovarian volume and follicle
      number decrease with age in women with PCOS and controls necessitating age-based
      criteria to define polycystic ovarian morphology. It is possible to use these
      criteria to distinguish PCOS in women over age 40 yr.

PMID- 19846741
TI  - Circulating and adipose tissue gene expression of zinc-alpha2-glycoprotein in
      obesity: its relationship with adipokine and lipolytic gene markers in
      subcutaneous and visceral fat.
AB  - CONTEXT: Zinc-alpha2-glycoprotein (ZAG) is a soluble protein similar to the class
      I major histocompatibility complex heavy chain, which has been implicated in
      lipid catabolism. We hypothesized that ZAG mRNA expression in adipose tissue may
      be linked with lipolytic and adipokine gene expression and have a close
      relationship with clinical phenotype. OBJECTIVES: The objective of the study was
      to analyze ZAG gene expression in human adipose tissue from lean and obese
      subjects. ZAG circulating plasma levels and its relationship with cardiometabolic
      risk factors were also studied. DESIGN: Seventy-three Caucasian (43 male and 30
      female) subjects were included. Plasma and adipose tissue [sc (SAT) and visceral
      (VAT)] from the same patient were studied. mRNA of PPARgamma, hormone-sensitive
      lipase (HSL), adipose triglyceride lipase, adiponectin, omentin, visfatin, and
      ZAG were quantified. Plasma concentrations of ZAG were determined with ELISA.
      RESULTS: ZAG plasma levels showed a negative correlation with insulin (r = -0.39;
      P = 0.008) and the homeostasis model assessment for insulin resistance index (r =
      -0.36; P = 0.016). No differences in ZAG circulating levels according to body
      mass index classification were observed. ZAG expression in SAT was significantly
      reduced in overweight and obese individuals compared with lean subjects (P <
      0.001 and P = 0.007, respectively). ZAG mRNA expression in both SAT and VAT
      depots were negatively correlated with many clinical and metabolic cardiovascular
      risk factors. After multiple linear regression analysis, SAT ZAG was mainly
      predicted by adiponectin mRNA expression (B = 0.993; P < 0.0001) and plasma
      triglyceride levels (B = -0.565; P = 0.006). VAT ZAG expression was predicted by
      adiponectin expression (B = 0.449; P < 0.0001), and HSL VAT expression (B =
      0.180; P = 0.023). CONCLUSIONS: The present study provides evidence of a role of
      ZAG gene in adipose tissue metabolism, with a close association with adiponectin
      gene expression in sc and visceral fat.

PMID- 19846743
TI  - Androgen replacement therapy in Turner syndrome: a pilot study.
AB  - CONTEXT: Women with Turner syndrome (TS) have reduced levels of androgens due to
      ovarian failure. HYPOTHESES: Morbidity associated with TS, such as bone
      fragility, metabolic changes, obesity, neurocognitive profile, and sexual
      problems may partly relate to androgen insufficiency and improve on androgen
      replacement therapy (ART). OBJECTIVES: The objective of the study was to
      determine the effect of androgens on morbidity in TS. DESIGN: Fourteen TS women
      (aged 17-27 yr) participated in a randomized, double-blind, placebo-controlled
      crossover pilot. The study was conducted in a hospital outpatient clinic between
      December 2001 and July 2004. INTERVENTION: TS patients were on estrogen/progestin
      replacement therapy. Subjects received oral 1.5 mg methyl testosterone (ART) or
      placebo for 1 yr and the alternative for another year. MAIN OUTCOME MEASURES: The
      study compared body composition as a primary outcome, and physiology,
      biochemistry, visceral fat, cognition, and quality of life (QOL) as secondary
      outcomes. RESULTS: ART as compared with placebo reduced total cholesterol,
      triglycerides, and high-density lipoprotein cholesterol. It improved bone mineral
      density, increased lean body mass, and decreased fat mass. ART improved
      attention, reaction time, and verbal memory and had no effect on executive
      functions and spatial cognition. Patients reported improved QOL, including
      general health, coping with stress, and sexual desire. CONCLUSIONS: Androgen
      insufficiency plays a role in TS-impaired body composition, neurocognition, and
      QOL, and these aspects improve with ART, which was safe and effective when given
      for 1 yr.

PMID- 19846742
TI  - Higher serum testosterone concentration in older women is associated with insulin
      resistance, metabolic syndrome, and cardiovascular disease.
AB  - CONTEXT: Early postmenopausal women with higher testosterone (T) levels have
      increased insulin resistance (IR) and cardiovascular risk factors, but whether
      this translates into increased cardiovascular disease later in life is unknown.
      OBJECTIVE: The objective of the study was to determine whether higher T levels
      are associated with IR, the metabolic syndrome (MetSyn), and coronary heart
      disease (CHD) in elderly women. DESIGN: Total T and free T by equilibrium
      dialysis were measured using ultrasensitive assays in 344 women aged 65-98 yr
      enrolled in the Cardiovascular Health Study. Cross-sectional analyses were
      performed to examine the associations between total and free T and IR, MetSyn,
      and CHD. RESULTS: There was a stepwise increase in the homeostasis model
      assessment of insulin resistance with increasing total (P = 0.0.003) and free T
      (P = 0.02) level and a corresponding decrease in Quantitative Insulin Sensitivity
      Check Index (P < 0.001 and P = 0.002, respectively). In adjusted models, higher
      levels of both total and free T were strongly associated with abdominal obesity
      and high fasting glucose, the two MetSyn components most strongly linked to IR.
      After adjustment, women in the top quartile of total T levels had a 3-fold
      greater odds of MetSyn (odds ratio 3.15, 95% confidence interval 1.57-6.35) than
      those in the bottom quartile and a 3-fold greater odds of CHD (odds ratio 2.95,
      95% confidence interval 1.2-7.3) than those in second quartile, whereas free T
      was not significantly associated with MetSyn or CHD. CONCLUSIONS: Higher levels
      of T are associated with IR, MetSyn, and CHD in elderly women. Whether T is a
      marker or mediator of cardiovascular disease in this population merits further
      investigation.

PMID- 19846745
TI  - Editorial Focus: Using phenotypic plasticity: focus on "Identification of renal
      transporters involved in sulfate excretion in marine teleost fish".

PMID- 19846744
TI  - Neonatal exendin-4 treatment reduces oxidative stress and prevents hepatic
      insulin resistance in intrauterine growth-retarded rats.
AB  - Intrauterine growth retardation (IUGR) has been linked to the development of type
      2 diabetes in adulthood. We have developed an IUGR model in the rat whereby the
      animals develop diabetes later in life. Previous studies demonstrate that
      administration of the long-acting glucagon-like-peptide-1 agonist, exendin-4,
      during the neonatal period prevents the development of diabetes in IUGR rats.
      IUGR animals exhibit hepatic insulin resistance early in life (prior to the onset
      of hyperglycemia), characterized by blunted suppression of hepatic glucose
      production (HGP) in response to insulin. Basal HGP is also significantly higher
      in IUGR rats. We hypothesized that neonatal administration of exendin-4 would
      prevent the development of hepatic insulin resistance. IUGR and control rats were
      given exendin-4 on days 1-6 of life. Hyperinsulinemic-euglycemic clamp studies
      showed that Ex-4 significantly reduced basal HGP by 20% and normalized insulin
      suppression of HGP in IUGR rats. While Ex-4 decreased body weight and fat content
      in both Control and IUGR animals, these differences were only statistically
      significant in Controls. Exendin-4 prevented development of oxidative stress in
      liver and reversed insulin-signaling defects in vivo, thereby preventing the
      development of hepatic insulin resistance. Defects in glucose disposal and
      suppression of hepatic glucose production in response to insulin were reversed.
      Similar results were obtained in isolated Ex-4-treated neonatal hepatocytes.
      These results indicate that exposure to exendin-4 in the newborn period reverses
      the adverse consequences of fetal programming and prevents the development of
      hepatic insulin resistance.

PMID- 19846747
TI  - Heterogeneous activity level of jaw-closing and -opening muscles and its
      association with arousal levels during sleep in the guinea pig.
AB  - Exaggerated jaw motor activities during sleep are associated with muscle symptoms
      in the jaw-closing rather than the jaw-opening muscles. The intrinsic activity of
      antagonistic jaw muscles during sleep remains unknown. This study aims to assess
      the balance of muscle activity between masseter (MA) and digastric (DG) muscles
      during sleep in guinea pigs. Electroencephalogram (EEG), electroocculogram, and
      electromyograms (EMGs) of dorsal neck, MA, and DG muscles were recorded with
      video during sleep-wake cycles. These variables were quantified for each 10-s
      epoch. The magnitude of muscle activity during sleep in relation to mean EMG
      activity of total wakefulness was up to three times higher for MA muscle than for
      DG muscle for nonrapid eye movement (NREM) and rapid-eye-movement (REM) sleep.
      Although the activity level of the two jaw muscles fluctuated during sleep, the
      ratio of activity level for each epoch was not proportional. Epochs with a high
      activity level for each muscle were associated with a decrease in deltaEEG power
      and/or an increase in heart rate in NREM sleep. However, this association with
      heart rate and activity levels was not observed in REM sleep. These results
      suggest that in guinea pigs, the magnitude of muscle activity for antagonistic
      jaw muscles is heterogeneously modulated during sleep, characterized by a high
      activity level in the jaw-closing muscle. Fluctuations in the activity are
      influenced by transient arousal levels in NREM sleep but, in REM sleep, the
      distinct controls may contribute to the fluctuation. The above intrinsic
      characteristics could underlie the exaggeration of jaw motor activities during
      sleep (e.g., sleep bruxism).

PMID- 19846746
TI  - Blood pressure and renal blow flow responses in heme oxygenase-2 knockout mice.
AB  - Heme oxygenase (HO) is the enzyme responsible for the breakdown of heme
      generating carbon monoxide (CO) and biliverdin in this process. HO-2 is the
      constitutively expressed isoform in most tissues, such as the kidney and
      vasculature. CO generated by HO is believed to be an important vasodilator in the
      renal circulation along with another gas, nitric oxide (NO). To determine the
      importance of HO-2 in the regulation of blood pressure and renal blood flow
      (RBF), we treated HO-2 knockout (KO) mice chronically with either ANG II or N(G)
      nitroarginine methyl ester (l-NAME). Basal blood pressures were not different
      between wild-type (WT), heterozygous (HET), or KO mice and averaged 113 +/- 3 vs.
      115 +/- 2 vs. 116 +/- 2 mmHg. Similar increases in blood pressure to chronic ANG
      II as well as l-NAME treatment were observed in all groups with blood pressures
      increasing an average of 30 mmHg in response to ANG II and 15 mmHg in response to
      l-NAME. Basal RBFs were not different between the groups averaging 6.0 +/- 0.5 (n
      = 6) vs. 4.8 +/- 0.6 (n = 10) vs. 5.8 +/- 0.7 (n = 6) ml*min(-1)*g(-1) kidney
      weight in WT, HET, and KO mice. HO-2 KO and HET mice exhibited an attenuated
      decrease in RBF in response to acute administration of ANG II, while no
      differences were observed with l-NAME. Our data indicate that blood pressure and
      RBF responses to increased ANG II or inhibition of nitric oxide are not
      significantly enhanced in HO-2 KO mice.

PMID- 19846748
TI  - Mechanisms of inhibition of T-type calcium current in the reticular thalamic
      neurons by 1-octanol: implication of the protein kinase C pathway.
AB  - Recent studies indicate that T-type calcium channels (T-channels) in the thalamus
      are cellular targets for general anesthetics. Here, we recorded T-currents and
      underlying low-threshold calcium spikes from neurons of nucleus reticularis
      thalami (nRT) in brain slices from young rats and investigated the mechanisms of
      their modulation by an anesthetic alcohol, 1-octanol. We found that 1-octanol
      inhibited native T-currents at subanesthetic concentrations with an IC(50) of
      approximately 4 muM. In contrast, 1-octanol was up to 30-fold less potent in
      inhibiting recombinant Ca(V)3.3 T-channels heterologously expressed in human
      embryonic kidney cells. Inhibition of both native and recombinant T-currents was
      accompanied by a hyperpolarizing shift in steady-state inactivation, indicating
      that 1-octanol stabilized inactive states of the channel. To explore the
      mechanisms underlying higher 1-octanol potency in inhibiting native nRT T
      currents, we tested the effect of the protein kinase C (PKC) activator phorbol 12
      myristate 13-acetate (PMA) and PKC inhibitors. We found that PMA caused a modest
      increase of T-current, whereas the inactive PMA analog 4alpha-PMA failed to
      affect T-current in nRT neurons. In contrast, 12-(2-cyanoethyl)-6,7,12,13
      tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Go 6976), an
      inhibitor of calcium-dependent PKC, decreased baseline T-current amplitude in nRT
      cells and abolished the effects of subsequently applied 1-octanol. The effects of
      1-octanol were also abolished by chelation of intracellular calcium ions with 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Taken together, these
      results suggest that inhibition of calcium-dependent PKC signaling is a possible
      molecular substrate for modulation of T-channels in nRT neurons by 1-octanol.

PMID- 19846749
TI  - An epilepsy-related region in the GABA(A) receptor mediates long-distance effects
      on GABA and benzodiazepine binding sites.
AB  - The GABA(A) receptor mutation gamma(2)R43Q causes absence epilepsy in humans.
      Homology modeling suggests that gamma(2)Arg43, gamma(2)Glu178, and beta(2)Arg117
      participate in a salt-bridge network linking the gamma(2) and beta(2) subunits.
      Here we show that several mutations at these locations exert similar long
      distance effects on other intersubunit interfaces involved in GABA and
      benzodiazepine binding. These mutations alter GABA-evoked receptor kinetics by
      slowing deactivation, enhancing desensitization, or both. Kinetic modeling and
      nonstationary noise analysis for gamma(2)R43Q reveal that these effects are due
      to slowed GABA unbinding and slowed recovery from desensitization. Both
      gamma(2)R43Q and beta(2)R117K also speed diazepam dissociation from the
      receptor's benzodiazepine binding interface, as assayed by the rate of decay of
      diazepam-induced potentiation of GABA-evoked currents. These data demonstrate
      that gamma(2)Arg43 and beta(2)Arg117 similarly regulate the stability of both the
      GABA and benzodiazepine binding sites at the distant beta/alpha and alpha/gamma
      intersubunit interfaces, respectively. A simple explanation for these results is
      that gamma(2)Arg43 and beta(2)Arg117 participate in interactions between the
      gamma(2) and beta(2) subunits, disruptions of which alter the neighboring
      intersubunit binding sites in a similar fashion. In addition, gamma(2)Arg43 and
      gamma(2)Glu178 regulate desensitization, probably mediated within the
      transmembrane domains near the pore. Therefore, mutations at the gamma/beta
      intersubunit interface have specific long-distance effects that are propagated
      widely throughout the GABA(A) receptor protein.

PMID- 19846751
TI  - Functional analysis and theoretical modeling of ferroportin reveals clustering of
      mutations according to phenotype.
AB  - Ferroportin disease is a heterogeneous iron release disorder resulting from
      mutations in the ferroportin gene. Ferroportin protein is a multitransmembrane
      domain iron transporter, responsible for iron export from cells, which, in turn,
      is regulated by the peptide hormone hepcidin. Mutations in the ferroportin gene
      may affect either regulation of the protein's transporter function or the ability
      of hepcidin to regulate iron efflux. We have used a combination of functional
      analysis of epitope-tagged ferroportin variants coupled with theoretical modeling
      to dissect the relationship between ferroportin mutations and their cognate
      phenotypes. Myc epitope-tagged human ferroportin expression constructs were
      transfected into Caco-2 intestinal cells and protein localization analyzed by
      immunofluorescence microscopy and colocalization with organelle markers. The
      effect of mutations on iron efflux was assessed by costaining with anti-ferritin
      antibodies and immunoblotting to quantitate cellular expression of ferritin and
      transferrin receptor 1. Wild-type ferroportin localized mainly to the cell
      surface and intracellular structures. All ferroportin disease-causing mutations
      studied had no effect on localization at the cell surface. N144H, N144T, and
      S338R mutant ferroportin retained the ability to transport iron. In contrast,
      A77D, V162Delta, and L170F mutants were iron transport defective. Surface
      staining experiments showed that both ends of the protein were located inside the
      cell. These data were used as the basis for theoretical modeling of the
      ferroportin molecule. The model predicted phenotypic clustering of mutations with
      gain-of-function variants associated with a hypothetical channel through the axis
      of ferroportin. Conversely, loss-of-function variants were located at the
      membrane/cytoplasm interface.

PMID- 19846750
TI  - Role of TRPC1 channel in skeletal muscle function.
AB  - Skeletal muscle contraction is reputed not to depend on extracellular Ca2+.
      Indeed, stricto sensu, excitation-contraction coupling does not necessitate entry
      of Ca2+. However, we previously observed that, during sustained activity
      (repeated contractions), entry of Ca2+ is needed to maintain force production. In
      the present study, we evaluated the possible involvement of the canonical
      transient receptor potential (TRPC)1 ion channel in this entry of Ca2+ and
      investigated its possible role in muscle function. Patch-clamp experiments reveal
      the presence of a small-conductance channel (13 pS) that is completely lost in
      adult fibers from TRPC1(-/-) mice. The influx of Ca2+ through TRPC1 channels
      represents a minor part of the entry of Ca(2+) into muscle fibers at rest, and
      the activity of the channel is not store dependent. The lack of TRPC1 does not
      affect intracellular Ca2+ concentration ([Ca2+](i)) transients reached during a
      single isometric contraction. However, the involvement of TRPC1-related Ca2+
      entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1(-/-)
      mice stimulated repeatedly progressively display lower [Ca2+](i) transients than
      those observed in TRPC1(+/+) fibers, and they also present an accentuated
      progressive loss of force. Interestingly, muscles from TRPC1(-/-) mice display a
      smaller fiber cross-sectional area, generate less force per cross-sectional area,
      and contain less myofibrillar proteins than their controls. They do not present
      other signs of myopathy. In agreement with in vitro experiments, TRPC1(-/-) mice
      present an important decrease of endurance of physical activity. We conclude that
      TRPC1 ion channels modulate the entry of Ca(2+) during repeated contractions and
      help muscles to maintain their force during sustained repeated contractions.

PMID- 19846752
TI  - Angiotensin II enhances hyperpolarization-activated currents in rat aortic
      baroreceptor neurons: involvement of superoxide.
AB  - As an endogenous physiologically active peptide, angiotensin (ANG) II plays an
      important role in the maintenance of blood pressure. In the arterial baroreceptor
      reflex (a pivotal regulator of blood pressure), aortic baroreceptor (AB) neurons
      located in the nodose ganglia (NG) are a primary afferent limb of the baroreflex.
      Hyperpolarization-activated currents (I(h)) in the AB neurons contribute to the
      excitability of the AB neurons. Therefore, the present study was to measure the
      modulating effect of ANG II on the I(h) in the primary AB neurons isolated from
      rats. Data from immunofluorescent and Western blot analyses showed that protein
      of AT(1) and AT(2) receptors was expressed in the nodose neurons. In the whole
      cell patch-clamp recording, ANG II concentration dependently enhanced the I(h)
      density in the AB neurons (100 nM ANG II-induced 53.8 +/- 3.8% increase for A
      type AB neurons and 30.4 +/- 7.7% increase for C-type AB neurons at test pulse 
      140 mV, P < 0.05). ANG II also decreased membrane excitability in the AB neurons.
      AT(1) receptor antagonist (1 muM losartan) but not AT(2) receptor antagonist (1
      muM PD-123,319) totally abolished the effect of ANG II on the I(h) and neuronal
      excitability. In addition, NADPH oxidase inhibitor (100 muM apocynin) and
      superoxide scavenger (1 mM tempol) also significantly blunted the ANG II-induced
      increase of the I(h) and decrease of the membrane excitability in the AB neurons.
      Furthermore, losartan, apocynin, or tempol significantly attenuated the
      superoxide overproduction in the NG tissues induced by ANG II. These results
      suggest that ANG II-NADPH oxidase-superoxide signaling can activate the I(h) and
      subsequently decrease the membrane excitability of rat AB neurons.

PMID- 19846753
TI  - Febrile-range temperature modifies cytokine gene expression in LPS-stimulated
      macrophages by differentially modifying NF-{kappa}B recruitment to cytokine gene
      promoters.
AB  - We previously showed that exposure to febrile-range temperatures (FRT, 39.5-40
      degrees C) reduces LPS-induced TNF-alpha expression, in part through the direct
      interaction of heat shock factor-1 (HSF1) with the TNF-alpha gene promoter.
      However, it is not known whether exposure to FRT also modifies more proximal LPS
      induced signaling events. Using HSF1-null mice, we confirmed that HSF1 is
      required for FRT-induced repression of TNF-alpha in vitro by LPS-stimulated bone
      marrow-derived macrophages and in vivo in mice challenged intratracheally with
      LPS. Exposing LPS-stimulated RAW 264.7 mouse macrophages to FRT reduced TNF-alpha
      expression while increasing IL-1beta expression despite the two genes sharing a
      common myeloid differentiation protein-88 (MyD88)-dependent pathway. Global
      activation of the three LPS-induced signaling intermediates that lead to cytokine
      gene expression, ERK and p38 MAPKs and NF-kappaB, was not affected by exposing
      RAW 264.7 cells to FRT as assessed by ERK and p38 phosphorylation and NF-kappaB
      in vitro DNA-binding activity and activation of a NF-kappaB-dependent synthetic
      promoter. However, chromatin immunoprecipitation (ChIP) analysis demonstrated
      that exposure to FRT reduced LPS-induced recruitment of NF-kappaB p65 to the TNF
      alpha promoter while simultaneously increasing its recruitment to the IL-1beta
      promoter. These data suggest that FRT exerts its effects on cytokine gene
      expression in a gene-specific manner through distal effects on promoter
      activation rather than proximal receptor activation and signal transduction.

PMID- 19846754
TI  - TGF-beta suppresses the upregulation of MMP-2 by vascular smooth muscle cells in
      response to PDGF-BB.
AB  - During platelet-derived growth factor (PDGF)-BB-mediated recruitment to
      neovascular sprouts, vascular smooth muscle cells (VSMCs) dedifferentiate from a
      contractile to a migratory phenotype. This involves the downregulation of
      contractile markers such as smooth muscle (SM) alpha-actin and the upregulation
      of promigration genes such as matrix metalloproteinase (MMP)-2. The regulation of
      MMP-2 in response to PDGF-BB is complex and involves both stimulatory and
      inhibitory signaling pathways, resulting in a significant delay in upregulation.
      Here, we provide evidence that the delay in MMP-2 upregulation may be due to the
      autocrine expression and activation of transforming growth factor (TGF)-beta,
      which is known to promote the contractile phenotype in VSMCs. Whereas PDGF-BB
      could induce the loss of stress fibers and focal adhesions, TGF-beta was able to
      block or reverse this transition to a noncontractile state. TGF-beta did not,
      however, suppress early signaling events stimulated by PDGF-BB. Over time, though
      PDGF-BB induced increased TGF-beta1 levels, it suppressed TGF-beta2 and TGF-beta3
      expression, leading to a net decrease in the total TGF-beta pool, resulting in
      the upregulation of MMP-2. Together, these findings indicate that MMP-2
      expression is suppressed by a threshold level of active TGF-beta, which in turn
      promotes a contractile VSMC phenotype that prevents the upregulation of MMP-2.

PMID- 19846756
TI  - Deregulation of apoptotic volume decrease and ionic movements in multidrug
      resistant tumor cells: role of chloride channels.
AB  - Changes in cell volume and ion gradients across the plasma membrane play a
      pivotal role in the initiation of apoptosis. Here we explore the kinetics of
      apoptotic volume decrease (AVD) and ion content dynamics in wild-type (WT) and
      multidrug-resistant (MDR) Ehrlich ascites tumor cells (EATC). In WT EATC,
      induction of apoptosis with cisplatin (5 muM) leads to three distinctive AVD
      stages: an early AVD(1) (4-12 h), associated with a 30% cell water loss; a
      transition stage AVD(T) ( approximately 12 to 32 h), where cell volume is partly
      recovered; and a secondary AVD(2) (past 32 h), where cell volume was further
      reduced. AVD(1) and AVD(2) were coupled to net loss of Cl(-), K(+), Na(+), and
      amino acids (ninhydrin-positive substances), whereas during AVD(T), Na(+) and Cl(
      ) were accumulated. MDR EATC was resistant to cisplatin, showing increased
      viability and less caspase 3 activation. Compared with WT EATC, MDR EATC
      underwent a less pronounced AVD(1,) an augmented AVD(T), and a delay in induction
      of AVD(2). Changes in AVD were associated with inhibition of Cl(-) loss during
      AVD(1), augmented NaCl uptake during AVD(T), and a delay of Cl(-) loss during
      AVD(2). Application of the anion channel inhibitor NS3728 inhibited AVD and
      completely abolished the differences in AVD, ionic movements, and caspase 3
      activation between WT and MDR EATC. Finally, the maximal capacity of volume
      regulated anion channel was found to be strongly repressed in MDR EATC. Together,
      these data suggest that impairment of AVD, primarily via modulation of NaCl
      movements, contribute to protection against apoptosis in MDR EATC.

PMID- 19846757
TI  - Polyploidy impairs human aortic endothelial cell function and is prevented by
      nicotinamide phosphoribosyltransferase.
AB  - Polyploid endothelial cells are found in aged and atherosclerotic arteries.
      However, whether increased chromosome content has an impact on endothelial cell
      function is unknown. We show here that human aortic endothelial cells become
      tetraploid as they approach replicative senescence. Furthermore, accumulation of
      tetraploid endothelial cells was accelerated during growth in high glucose.
      Interestingly, induction of polyploidy was completely prevented by modest
      overexpression of the NAD+ regenerating enzyme, nicotinamide
      phosphoribosyltransferase (Nampt). To determine the impact of polyploidy on
      endothelial cell function, independent of replicative senescence, we induced
      tetraploidy using the spindle poison, nocodazole. Global gene expression analyses
      of tetraploid endothelial cells revealed a dysfunctional phenotype characterized
      by a cell cycle arrest profile (decreased CCNE2/A2, RBL1, BUB1B; increased
      CDKN1A) and increased expression of genes involved in inflammation (IL32,
      TNFRSF21/10C, PTGS1) and extracellular matrix remodeling (COL5A1, FN1, MMP10/14).
      The protection from polyploidy conferred by Nampt was not associated with
      enhanced poly(ADP-ribose) polymerase-1 or sirtuin (SIRT) 2 activity, but with
      increased SIRT1 activity, which reduced cellular reactive oxygen species and the
      associated oxidative stress stimulus for the induction of polyploidy. We conclude
      that human aortic endothelial cells are prone to chromosome duplication that, in
      and of itself, can induce characteristics of endothelial dysfunction. Moreover,
      the emergence of polyploid endothelial cells during replicative aging and glucose
      overload can be prevented by optimizing the Nampt-SIRT1 axis.

PMID- 19846755
TI  - Elevated Ca2+ sparklet activity during acute hyperglycemia and diabetes in
      cerebral arterial smooth muscle cells.
AB  - Ca(+) sparklets are subcellular Ca(2+) signals produced by the opening of L-type
      Ca(2+) channels (LTCCs). In cerebral arterial myocytes, Ca(2+) sparklet activity
      varies regionally, resulting in low and high activity, "persistent" Ca(2+)
      sparklet sites. Although increased Ca(2+) influx via LTCCs in arterial myocytes
      has been implicated in the chain of events contributing to vascular dysfunction
      during acute hyperglycemia and diabetes, the mechanisms underlying these
      pathological changes remain unclear. Here, we tested the hypothesis that
      increased Ca(2+) sparklet activity contributes to higher Ca(2+) influx in
      cerebral artery smooth muscle during acute hyperglycemia and in an animal model
      of non-insulin-dependent, type 2 diabetes: the dB/dB mouse. Consistent with this
      hypothesis, acute elevation of extracellular glucose from 10 to 20 mM increased
      the density of low activity and persistent Ca(2+) sparklet sites as well as the
      amplitude of LTCC currents in wild-type cerebral arterial myocytes. Furthermore,
      Ca(2+) sparklet activity and LTCC currents were higher in dB/dB than in control
      myocytes. We found that activation of PKA contributed to higher Ca(2+) sparklet
      activity during hyperglycemia and diabetes. In addition, we found that the
      interaction between PKA and the scaffolding protein A-kinase anchoring protein
      was critical for the activation of persistent Ca(2+) sparklets by PKA in cerebral
      arterial myocytes after hyperglycemia. Accordingly, PKA inhibition equalized
      Ca(2+) sparklet activity between dB/dB and wild-type cells. These findings
      suggest that hyperglycemia increases Ca(2+) influx by increasing Ca(2+) sparklet
      activity via a PKA-dependent pathway in cerebral arterial myocytes and
      contributes to vascular dysfunction during diabetes.

PMID- 19846758
TI  - Transporters beyond transport. Focus on "Deregulation of apoptotic volume
      decrease and ionic movements in multidrug-resistant tumor cells: role of chloride
      channels".

PMID- 19846759
TI  - Long-term therapeutic and orthotic effects of a foot drop stimulator on walking
      performance in progressive and nonprogressive neurological disorders.
AB  - BACKGROUND: Stimulators applying functional electrical stimulation (FES) to the
      common peroneal nerve improve walking with a foot drop, which occurs in several
      disorders. OBJECTIVE: To compare the orthotic and therapeutic effects of a foot
      drop stimulator on walking performance of subjects with chronic nonprogressive
      (eg, stroke) and progressive (eg, multiple sclerosis) disorders. METHODS:
      Subjects with nonprogressive (41) and progressive (32) conditions used a foot
      drop stimulator for 3 to 12 months while walking in the community. Walking speed
      was measured with a 10-m test and a 4-minute figure-8 test; physiological cost
      index (PCI) and device usage were also measured. The subjects were tested with
      FES on and off (orthotic effect) before and after (therapeutic effect) stimulator
      use. RESULTS: After 3 months of FES use, the nonprogressive and progressive
      groups had a similar, significant orthotic effect (5.0% and 5.7%, respectively, P
      < .003; percentage change in mean values) and therapeutic effect with FES off
      (17.8% and 9.1%, respectively, P < .005) on figure-8 walking speed. Overall, PCI
      showed a decreasing trend (P = .031). The therapeutic effect on figure-8 speed
      diverged later between both groups to 28.0% (P < .001) and 7.9% at 11 months. The
      combined therapeutic plus orthotic effect on figure-8 speed at 11 months was,
      respectively, 37.8% (P < .001) and 13.1% (P = .012); PCI decreased 18.2% (P =
      .038) and 6.5%, respectively. CONCLUSIONS: Subjects with progressive and
      nonprogressive disorders had an orthotic benefit from FES up to 11 months. The
      therapeutic effect increased for 11 months in nonprogressive disorders but only
      for 3 months in progressive disorders. The combined effect remained significant
      and clinically relevant.

PMID- 19846760
TI  - Mapping of multiple susceptibility variants within the MHC region for 7 immune
      mediated diseases.
AB  - The human MHC represents the strongest susceptibility locus for autoimmune
      diseases. However, the identification of the true predisposing gene(s) has been
      handicapped by the strong linkage disequilibrium across the region. Furthermore,
      most studies to date have been limited to the examination of a subset of the HLA
      and non-HLA genes with a marker density and sample size insufficient for mapping
      all independent association signals. We genotyped a panel of 1,472 SNPs to
      capture the common genomic variation across the 3.44 megabase (Mb) classic MHC
      region in 10,576 DNA samples derived from patients with systemic lupus
      erythematosus, Crohn's disease, ulcerative colitis, rheumatoid arthritis,
      myasthenia gravis, selective IgA deficiency, multiple sclerosis, and appropriate
      control samples. We identified the primary association signals for each disease
      and performed conditional regression to identify independent secondary signals.
      The data demonstrate that MHC associations with autoimmune diseases result from
      complex, multilocus effects that span the entire region.

PMID- 19846761
TI  - 26G endo-siRNAs regulate spermatogenic and zygotic gene expression in
      Caenorhabditis elegans.
AB  - Endogenous small interfering RNAs (endo-siRNAs) regulate diverse gene expression
      programs in eukaryotes by either binding and cleaving mRNA targets or mediating
      heterochromatin formation; however, the mechanisms of endo-siRNA biogenesis,
      sorting, and target regulation remain poorly understood. Here we report the
      identification and function of a specific class of germline-generated endo-siRNAs
      in Caenorhabditis elegans that are 26 nt in length and contain a guanine at the
      first nucleotide position (i.e., 26G RNAs). 26G RNAs regulate gene expression
      during spermatogenesis and zygotic development, and their biogenesis requires the
      ERI-1 exonuclease and the RRF-3 RNA-dependent RNA polymerase (RdRP). Remarkably,
      we identified two nonoverlapping subclasses of 26G RNAs that sort into specific
      RNA-induced silencing complexes (RISCs) and differentially regulate distinct mRNA
      targets. Class I 26G RNAs target genes are expressed during spermatogenesis,
      whereas class II 26G RNAs are maternally inherited and silence gene expression
      during zygotic development. These findings implicate a class of endo-siRNAs in
      the global regulation of transcriptional programs required for fertility and
      development.

PMID- 19846762
TI  - T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and
      Tgfbeta2 expression and endocardial cushion formation.
AB  - During early heart development, Tbx2 gene expression is initiated in the cardiac
      crescent and then becomes restricted to the outflow tract and the
      atrioventricular region. We identified a Tbx2 regulatory region, enriched in
      multiple Smad sites, sufficient to reproduce Tbx2 expression patterns overlapping
      Bmp2 and Bmp4 gene activity in the heart. The role of Tbx2 in cardiogenesis was
      analyzed by using Cre-LoxP activated Tbx2 transgenic misexpression in chamber
      myocardium. Ventricular Tbx2 misexpression exhibited an abnormally narrow chamber
      lumen owing to the expansion of Hyaluronan synthase 2 expression in the ECM or
      cardiac jelly and the appearance of the endocardial cushions (ECs). Excessive
      Tbx2 also induced Tgfbeta2, which coincided with the outgrowth epithelial
      mesenchymal transformed cells in ventricular and atrial tissues modifying
      cardiomyocyte identity from chamber type to non-chamber type. Tbx2, a central
      intermediary of Bmp-Smad signaling, has a central part in directing Has2 and
      Tgfbeta2 expression, facilitating EC formation.

PMID- 19846763
TI  - A role for the ventral premotor cortex beyond performance monitoring.
AB  - Depending on the circumstances, decision making requires either comparing current
      sensory information with that showed recently or with that recovered from long
      term memory (LTM). In both cases, to learn from past decisions and adapt future
      ones, memories and outcomes have to be available after the report of a decision.
      The ventral premotor cortex (PMv) is a good candidate for integrating memory
      traces and outcomes because it is involved in working-memory, decision-making,
      and encoding the outcomes. To test this hypothesis we recorded the extracellular
      unit activity while monkeys performed 2 variants of a visual discrimination task.
      In one task, the decision was based on the comparison of the orientation of a
      current stimulus with that of another stimulus recently shown. In the other task,
      the monkeys had to compare the current orientation of the stimulus with the
      correct one retrieved from LTM. Here, we report that when the task required
      retrieval of the stimulus and its use in the following trials, the neurons
      continue encoding this internal representation together with the outcomes after
      the monkey has emitted the motor response. However, this codification did not
      occur when the stimulus was shown recently and updated every trial. These results
      suggest that the PMv activity represents the information needed to evaluate the
      consequences of a decision. We interpret these results as evidence that the PMv
      plays a role in evaluating the outcomes that can serve to learn and thus adapt
      future decision to environmental demands.

PMID- 19846764
TI  - An aspartate and a water molecule mediate efficient acid-base catalysis in a
      tailored antibody pocket.
AB  - Design of catalysts featuring multiple functional groups is a desirable, yet
      formidable goal. Antibody 13G5, which accelerates the cleavage of unactivated
      benzisoxazoles, is one of few artificial enzymes that harness an acid and a base
      to achieve efficient proton transfer. X-ray structures of the Fab-hapten
      complexes of wild-type 13G5 and active-site variants now afford detailed insights
      into its mechanism. The parent antibody preorganizes Asp(H35) and Glu(L34) to
      abstract a proton from substrate and to orient a water molecule for leaving group
      stabilization, respectively. Remodeling the environment of the hydrogen bond
      donor with a compensatory network of ordered waters, as seen in the Glu(L34) to
      alanine mutant, leads to an impressive 10(9)-fold rate acceleration over the
      nonenzymatic reaction with acetate, illustrating the utility of buried water
      molecules in bifunctional catalysis. Generalization of these design principles
      may aid in creation of catalysts for other important chemical transformations.

PMID- 19846765
TI  - Resolving the evolution of extant and extinct ruminants with high-throughput
      phylogenomics.
AB  - The Pecorans (higher ruminants) are believed to have rapidly speciated in the Mid
      Eocene, resulting in five distinct extant families: Antilocapridae, Giraffidae,
      Moschidae, Cervidae, and Bovidae. Due to the rapid radiation, the Pecoran
      phylogeny has proven difficult to resolve, and 11 of the 15 possible rooted
      phylogenies describing ancestral relationships among the Antilocapridae,
      Giraffidae, Cervidae, and Bovidae have each been argued as representations of the
      true phylogeny. Here we demonstrate that a genome-wide single nucleotide
      polymorphism (SNP) genotyping platform designed for one species can be used to
      genotype ancient DNA from an extinct species and DNA from species diverged up to
      29 million years ago and that the produced genotypes can be used to resolve the
      phylogeny for this rapidly radiated infraorder. We used a high-throughput assay
      with 54,693 SNP loci developed for Bos taurus taurus to rapidly genotype 678
      individuals representing 61 Pecoran species. We produced a highly resolved
      phylogeny for this diverse group based upon 40,843 genome-wide SNP, which is five
      times as many informative characters as have previously been analyzed. We also
      establish a method to amplify and screen genomic information from extinct
      species, and place Bison priscus within the Bovidae. The quality of genotype
      calls and the placement of samples within a well-supported phylogeny may provide
      an important test for validating the fidelity and integrity of ancient samples.
      Finally, we constructed a phylogenomic network to accurately describe the
      relationships between 48 cattle breeds and facilitate inferences concerning the
      history of domestication and breed formation.

PMID- 19846766
TI  - Quantitative proteomic analysis of single pancreatic islets.
AB  - Technological developments make mass spectrometry (MS)-based proteomics a central
      pillar of biochemical research. MS has been very successful in cell culture
      systems, where sample amounts are not limiting. To extend its capabilities to
      extremely small, physiologically distinct cell types isolated from tissue, we
      developed a high sensitivity chromatographic system that measures nanogram
      protein mixtures for 8 h with very high resolution. This technology is based on
      splitting gradient effluents into a capture capillary and provides an inherent
      technical replicate. In a single analysis, this allowed us to characterize kidney
      glomeruli isolated by laser capture microdissection to a depth of more than 2,400
      proteins. From pooled pancreatic islets of Langerhans, another type of
      "miniorgan," we obtained an in-depth proteome of 6,873 proteins, many of them
      involved in diabetes. We quantitatively compared the proteome of single islets,
      containing 2,000-4,000 cells, treated with high or low glucose levels, and
      covered most of the characteristic functions of beta cells. Our ultrasensitive
      analysis recapitulated known hyperglycemic changes but we also find components up
      regulated such as the mitochondrial stress regulator Park7. Direct proteomic
      analysis of functionally distinct cellular structures opens up perspectives in
      physiology and pathology.

PMID- 19846767
TI  - In ovo application of antagomiRs indicates a role for miR-196 in patterning the
      chick axial skeleton through Hox gene regulation.
AB  - Patterning of the vertebrate axial skeleton requires precise spatial and temporal
      control of Hox gene expression during embryonic development. MicroRNAs (miRNAs)
      are recently described modulators of gene activity, and members of the miR-196
      and miR-10 families have been shown to target several Hox genes in vivo. Testing
      miRNA function in mice is complicated by potential redundancy between family
      members. To circumvent this, we have developed protocols for introducing modified
      antisense oligonucleotides (antagomiRs) in ovo during chick development. Using
      this approach, we identify a layer of regulatory control provided by the miR-196
      family in defining the boundary of Hox gene expression along the anterior
      posterior (A-P) embryonic axis. Following knockdown of miR-196, we observe a
      homeotic transformation of the last cervical vertebrae toward a thoracic
      identity. This phenotypic alteration is, in part, due to an anterior expansion of
      Hoxb8 gene expression and consolidates the in vivo relevance of post
      transcriptional Hox gene regulation provided by miRNAs in the complex hierarchies
      governing axial pattering.

PMID- 19846768
TI  - Paper-supported 3D cell culture for tissue-based bioassays.
AB  - Fundamental investigations of human biology, and the development of therapeutics,
      commonly rely on 2D cell-culture systems that do not accurately recapitulate the
      structure, function, or physiology of living tissues. Systems for 3D cultures
      exist but do not replicate the spatial distributions of oxygen, metabolites, and
      signaling molecules found in tissues. Microfabrication can create architecturally
      complex scaffolds for 3D cell cultures that circumvent some of these limitations;
      unfortunately, these approaches require instrumentation not commonly available in
      biology laboratories. Here we report that stacking and destacking layers of paper
      impregnated with suspensions of cells in extracellular matrix hydrogel makes it
      possible to control oxygen and nutrient gradients in 3D and to analyze molecular
      and genetic responses. Stacking assembles the "tissue", whereas destacking
      disassembles it, and allows its analysis. Breast cancer cells cultured within
      stacks of layered paper recapitulate behaviors observed both in 3D tumor
      spheroids in vitro and in tumors in vivo: Proliferating cells in the stacks
      localize in an outer layer a few hundreds of microns thick, and growth-arrested,
      apoptotic, and necrotic cells concentrate in the hypoxic core where hypoxia
      sensitive genes are overexpressed. Altering gas permeability at the ends of
      stacks controlled the gradient in the concentration of the O(2) and was
      sufficient by itself to determine the distribution of viable cells in 3D. Cell
      cultures in stacked, paper-supported gels offer a uniquely flexible approach to
      study cell responses to 3D molecular gradients and to mimic tissue- and organ
      level functions.

PMID- 19846769
TI  - A hydroxycinnamoyltransferase responsible for synthesizing suberin aromatics in
      Arabidopsis.
AB  - Suberin, a polyester polymer in the cell wall of terrestrial plants, controls the
      transport of water and nutrients and protects plant from pathogenic infections
      and environmental stresses. Structurally, suberin consists of aliphatic and
      aromatic domains; p-hydroxycinnamates, such as ferulate, p-coumarate, and/or
      sinapate, are the major phenolic constituents of the latter. By analyzing the
      "wall-bound" phenolics of mutant lines of Arabidopsis deficient in a family of
      acyl-CoA dependent acyltransferase (BAHD) genes, we discovered that the formation
      of aromatic suberin in Arabidopsis, primarily in seed and root tissues, depends
      on a member of the BAHD superfamily of enzymes encoded by At5g41040. This enzyme
      exhibits an omega-hydroxyacid hydroxycinnamoyltransferase activity with an in
      vitro kinetic preference for feruloyl-CoA and 16-hydroxypalmitic acid. Knocking
      down or knocking out the At5g41040 gene in Arabidopsis reduces specifically the
      quantity of ferulate in suberin, but does not affect the accumulation of p
      coumarate or sinapate. The loss of the suberin phenolic differentially affects
      the aliphatic monomer loads and alters the permeability and sensitivity of seeds
      and roots to salt stress. This highlights the importance of suberin aromatics in
      the polymer's function.

PMID- 19846770
TI  - Five-month-old infants' identification of the sources of vocalizations.
AB  - Humans speak, monkeys grunt, and ducks quack. How do we come to know which
      vocalizations animals produce? Here we explore this question by asking whether
      young infants expect humans, but not other animals, to produce speech, and
      further, whether infants have similarly restricted expectations about the sources
      of vocalizations produced by other species. Five-month-old infants matched
      speech, but not human nonspeech vocalizations, specifically to humans, looking
      longer at static human faces when human speech was played than when either rhesus
      monkey or duck calls were played. They also matched monkey calls to monkey faces,
      looking longer at static rhesus monkey faces when rhesus monkey calls were played
      than when either human speech or duck calls were played. However, infants failed
      to match duck vocalizations to duck faces, even though infants likely have more
      experience with ducks than monkeys. Results show that by 5 months of age, human
      infants generate expectations about the sources of some vocalizations, mapping
      human faces to speech and rhesus faces to rhesus calls. Infants' matching
      capacity does not appear to be based on a simple associative mechanism or
      restricted to their specific experiences. We discuss these findings in terms of
      how infants may achieve such competence, as well as its specificity and relevance
      to acquiring language.

PMID- 19846772
TI  - Lack of association of three primary open-angle glaucoma-susceptible loci with
      primary glaucomas in an Indian population.

PMID- 19846771
TI  - Elevated CO2 suppresses specific Drosophila innate immune responses and
      resistance to bacterial infection.
AB  - Elevated CO(2) levels (hypercapnia) frequently occur in patients with obstructive
      pulmonary diseases and are associated with increased mortality. However, the
      effects of hypercapnia on non-neuronal tissues and the mechanisms that mediate
      these effects are largely unknown. Here, we develop Drosophila as a genetically
      tractable model for defining non-neuronal CO(2) responses and response pathways.
      We show that hypercapnia significantly impairs embryonic morphogenesis, egg
      laying, and egg hatching even in mutants lacking the Gr63a neuronal CO(2) sensor.
      Consistent with previous reports that hypercapnic acidosis can suppress mammalian
      NF-kappaB-regulated innate immune genes, we find that in adult flies and the
      phagocytic immune-responsive S2* cell line, hypercapnia suppresses induction of
      specific antimicrobial peptides that are regulated by Relish, a conserved Rel/NF
      kappaB family member. Correspondingly, modest hypercapnia (7-13%) increases
      mortality of flies inoculated with E. faecalis, A. tumefaciens, or S. aureus.
      During E. faecalis and A. tumefaciens infection, increased bacterial loads were
      observed, indicating that hypercapnia can decrease host resistance. Hypercapnic
      immune suppression is not mediated by acidosis, the olfactory CO(2) receptor
      Gr63a, or by nitric oxide signaling. Further, hypercapnia does not induce
      responses characteristic of hypoxia, oxidative stress, or heat shock. Finally,
      proteolysis of the Relish IkappaB-like domain is unaffected by hypercapnia,
      indicating that immunosuppression acts downstream of, or in parallel to, Relish
      proteolytic activation. Our results suggest that hypercapnic immune suppression
      is mediated by a conserved response pathway, and illustrate a mechanism by which
      hypercapnia could contribute to worse outcomes of patients with advanced lung
      disease, who frequently suffer from both hypercapnia and respiratory infections.

PMID- 19846773
TI  - Profile of Steve Kay.

PMID- 19846774
TI  - Shape transition during nest digging in ants.
AB  - Nest building in social insects is among the collective processes that show
      highly conservative features such as basic modules (chambers and galleries) or
      homeostatic properties. Although ant nests share common characteristics, they
      exhibit a high structural variability, of which morphogenesis and underlying
      mechanisms remain largely unknown. We conducted two-dimensional nest-digging
      experiments under homogeneous laboratory conditions to investigate the shape
      diversity that emerges only from digging dynamics and without the influence of
      any environmental heterogeneity. These experiments revealed that, during the
      excavation, a morphological transition occurs because the primary circular cavity
      evolves into a ramified structure through a branching process. Such a transition
      is observed, whatever the number of ants involved, but occurs more frequently for
      a larger number of workers. A stochastic model highlights the central role of
      density effects in shape transition. These results indicate that nest digging
      shares similar properties with various physical, chemical, and biological
      systems. Moreover, our model of morphogenesis provides an explanatory framework
      for shape transitions in decentralized growing structures in group-living
      animals.

PMID- 19846775
TI  - Microsomal prostaglandin E synthase 1 determines tumor growth in vivo of prostate
      and lung cancer cells.
AB  - There is strong evidence for a role of prostaglandin E(2) (PGE(2)) in cancer cell
      proliferation and tumor development. In PGE(2) biosynthesis, cyclooxygenases (COX
      1/COX-2) convert arachidonic acid to PGH(2), which can be isomerized to PGE(2) by
      microsomal PGE-synthase-1 (MPGES-1). The human prostate cancer cell line DU145
      expressed high amounts of MPGES-1 in a constitutive manner. MPGES-1 expression
      also was detectable in human prostate cancer tissues, where it appeared more
      abundant compared with benign hyperplasia. By using shRNA, we established stable
      and practically complete knockdown of MPGES-1, both in DU145 cells with high
      constitutive expression and in the non-small cell lung cancer cell line A549,
      where MPGES-1 is inducible. For microsomes prepared from knockdown clones,
      conversion of PGH(2) to PGE(2) was reduced by 85-90%. This resulted in clear
      phenotypic changes: MPGES-1 knockdown conferred decreased clonogenic capacity and
      slower growth of xenograft tumors (with disintegrated tissue structure) in nude
      mice. For DU145 cells, MPGES-1 knockdown gave increased apoptosis in response to
      genotoxic stress (adriamycin), which could be rescued by exogenous PGE(2). The
      results suggest that MPGES-1 is an alternative therapeutic target in cancer cells
      expressing this enzyme.

PMID- 19846776
TI  - PTEN dosage is essential for neurofibroma development and malignant
      transformation.
AB  - Patients with neurofibromatosis type 1 (NF1) carry approximately a 10% lifetime
      risk of developing a malignant peripheral nerve sheath tumor (MPNST). Although
      the molecular mechanisms underlying NF1 to MPNST malignant transformation remain
      unclear, alterations of both the RAS/RAF/MAPK and PI3K/AKT/mTOR signaling
      pathways have been implicated. In a series of genetically engineered murine
      models, we perturbed RAS/RAF/MAPK or/and PTEN/PI3K/AKT pathway, individually or
      simultaneously, via conditional activation of K-ras oncogene or deletion of Nf1
      or Pten tumor suppressor genes. Only K-Ras activation in combination with a
      single Pten allele deletion led to 100% penetrable development of NF lesions and
      subsequent progression to MPNST. Importantly, loss or decrease in PTEN expression
      was found in all murine MPNSTs and a majority of human NF1-associated MPNST
      lesions, suggesting that PTEN dosage and its controlled signaling pathways are
      critical for transformation of NFs to MPNST. Using noninvasive in vivo PET-CT
      imaging, we demonstrated that FDG can be used to identify the malignant
      transformation in both murine and human MPNSTs. Our data suggest that combined
      inhibition of RAS/RAF/MAPK and PTEN/PI3K/AKT pathways may be beneficial for
      patients with MPNST.

PMID- 19846777
TI  - A transcription switch toggled by noncoding RNAs.

PMID- 19846778
TI  - Ultrafast photochemistry of methyl hydroperoxide on ice particles.
AB  - Simulations show that photodissociation of methyl hydroperoxide, CH(3)OOH, on
      water clusters produces a surprisingly wide range of products on a subpicosecond
      time scale, pointing to the possibility of complex photodegradation pathways for
      organic peroxides on aerosols and water droplets. Dynamics are computed at
      several excitation energies at 50 K using a semiempirical PM3 potential surface.
      CH(3)OOH is found to prefer the exterior of the cluster, with the CH(3)O group
      sticking out and the OH group immersed within the cluster. At atmospherically
      relevant photodissociation wavelengths the OH and CH(3)O photofragments remain at
      the surface of the cluster or embedded within it. However, none of the 25
      completed trajectories carried out at the atmospherically relevant
      photodissociation energies led to recombination of OH and CH(3)O to form
      CH(3)OOH. Within the limited statistics of the available trajectories the
      predicted yield for the recombination is zero. Instead, various reactions
      involving the initial fragments and water promptly form a wide range of stable
      molecular products such as CH(2)O, H(2)O, H(2), CO, CH(3)OH, and H(2)O(2).

PMID- 19846779
TI  - Structural basis for the high Ca2+ affinity of the ubiquitous SERCA2b Ca2+ pump.
AB  - Sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) Ca(2+) transporters pump
      cytosolic Ca(2+) into the endoplasmic reticulum, maintaining a Ca(2+) gradient
      that controls vital cell functions ranging from proliferation to death. To meet
      the physiological demand of the cell, SERCA activity is regulated by adjusting
      the affinity for Ca(2+) ions. Of all SERCA isoforms, the housekeeping SERCA2b
      isoform displays the highest Ca(2+) affinity because of a unique C-terminal
      extension (2b-tail). Here, an extensive structure-function analysis of SERCA2b
      mutants and SERCA1a2b chimera revealed how the 2b-tail controls Ca(2+) affinity.
      Its transmembrane (TM) segment (TM11) and luminal extension functionally
      cooperate and interact with TM7/TM10 and luminal loops of SERCA2b, respectively.
      This stabilizes the Ca(2+)-bound E1 conformation and alters Ca(2+)-transport
      kinetics, which provides the rationale for the higher apparent Ca(2+) affinity.
      Based on our NMR structure of TM11 and guided by mutagenesis results, a
      structural model was developed for SERCA2b that supports the proposed 2b-tail
      mechanism and is reminiscent of the interaction between the alpha- and beta
      subunits of Na(+),K(+)-ATPase. The 2b-tail interaction site may represent a novel
      target to increase the Ca(2+) affinity of malfunctioning SERCA2a in the failing
      heart to improve contractility.

PMID- 19846780
TI  - Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition.
AB  - The Esx secretion pathway is conserved across Gram-positive bacteria. Esx-1, the
      best-characterized system, is required for virulence of Mycobacterium
      tuberculosis, although its precise function during infection remains unclear. Esx
      3, a paralogous system present in all mycobacterial species, is required for
      growth in vitro. Here, we demonstrate that mycobacteria lacking Esx-3 are
      defective in acquiring iron. To compete for the limited iron available in the
      host and the environment, these organisms use mycobactin, high-affinity iron
      binding molecules. In the absence of Esx-3, mycobacteria synthesize mycobactin
      but are unable to use the bound iron and are impaired severely for growth during
      macrophage infection. Mycobacteria thus require a specialized secretion system
      for acquiring iron from siderophores.

PMID- 19846781
TI  - Role of band 3 in regulating metabolic flux of red blood cells.
AB  - Deoxygenation elevates glycolytic flux and lowers pentose phosphate pathway (PPP)
      activity in mammalian erythrocytes. The membrane anion transport protein (band 3
      or AE1) is thought to facilitate this process by binding glycolytic enzymes (GEs)
      and inhibiting their activity in an oxygen-dependent manner. However, this
      regulatory mechanism has not been demonstrated under physiological conditions. In
      this study, we introduce a (1)H-(13)C NMR technique for measuring metabolic
      fluxes in intact cells. The role of band 3 in mediating the
      oxygenated/deoxygenated metabolic transition was examined by treating cells with
      pervanadate, a reagent that prevents the GE-band 3 complex from forming. We
      report that pervanadate suppresses oxygen-dependent changes in glycolytic and PPP
      fluxes. Moreover, these metabolic alterations were not attributable to modulation
      of bisphosphoglycerate mutase, direct inhibition of GEs by pervanadate, or
      oxidation, which are the major side effects of pervanadate treatment. These data
      provide direct evidence supporting the role of band 3 in mediating oxygen
      regulated metabolic transitions.

PMID- 19846782
TI  - Peeling back the mystery of DNA overstretching.

PMID- 19846783
TI  - Interrogating functional integration between injected pluripotent stem cell
      derived cells and surrogate cardiac tissue.
AB  - Myocardial infarction resulting in irreversible loss of cardiomyocytes (CMs)
      remains a leading cause of heart failure. Although cell transplantation has
      modestly improved cardiac function, major challenges including increasing cell
      survival, engraftment, and functional integration with host tissue, remain.
      Embryonic stem cells (ESCs), which can be differentiated into cardiac progenitors
      (CPs) and CMs, represent a candidate cell source for cardiac cell therapy.
      However, it is not known what specific cell type or condition is the most
      appropriate for transplantation. This problem is exasperated by the lack of
      efficient and predictive strategies to screen the large numbers of parameters
      that may impact cell transplantation. We used a cardiac tissue model, engineered
      heart tissue (EHT), and quantitative molecular and electrophysiological analyses,
      to test transplantation conditions and specific cell populations for their
      potential to functionally integrate with the host tissue. In this study, we
      validated our analytical platform using contractile mouse neonatal CMs (nCMs) and
      noncontractile cardiac fibroblasts (cFBs), and screened for the integration
      potential of ESC-derived CMs and CPs (ESC-CMs and -CPs). Consistent with previous
      in vivo studies, cFB injection interfered with electrical signal propagation,
      whereas injected nCMs improved tissue function. Purified bioreactor-generated ESC
      CMs exhibited a diminished capacity for electrophysiological integration; a
      result correlated with lower (compared with nCMs) connexin 43 expression. ESC
      CPs, however, appeared able to appropriately mature and integrate into EHT,
      enhancing the amplitude of tissue contraction. Our results support the use of EHT
      as a model system to accelerate development of cardiac cell therapy strategies.

PMID- 19846784
TI  - Downregulating the sucrose transporter VpSUT1 in Verbascum phoeniceum does not
      inhibit phloem loading.
AB  - Sucrose is loaded into the phloem in the minor veins of leaves before export. Two
      active, species-specific loading mechanisms have been proposed. One involves
      transporter-mediated sucrose transfer from the apoplast into the sieve element
      companion cell complex, so-called apoplastic loading. In the putative second
      mechanism, sucrose follows an entirely symplastic pathway, and the solute
      concentration is elevated by the synthesis of raffinose and stachyose in the
      phloem, not by transporter activity. Several sucrose-transporting plants have
      been shown to be apoplastic loaders by downregulating sucrose transporter 1
      (SUT1), leading to accumulation of sugars and leaf chlorosis. In this study we
      compared the effect of downregulating SUT1 in Nicotiana tabacum, a sucrose
      transporter, and Verbascum phoeniceum, a species that transports raffinose and
      stachyose. To test the effectiveness of RNAi downregulation, we measured SUT1
      mRNA levels and sucrose-H(+) symport in leaf discs. Mild NtSUT1 downregulation in
      N. tabacum resulted in the pronounced phenotype associated with loading
      inhibition. In contrast, no such phenotype developed when VpSUT1 was
      downregulated in V. phoeniceum, leaving minimal sucrose transport activity. Only
      those plants with the most severe VpSUT1 downregulation accumulated more
      carbohydrate than usual and these plants were normal by other criteria: growth
      rate, photosynthesis, and ability to clear starch during the night. The results
      provide direct evidence that the mechanism of phloem loading in V. phoeniceum
      does not require active sucrose uptake from the apoplast and strongly supports
      the conclusion that the loading pathway is symplastic in this species.

PMID- 19846785
TI  - Bothnia dystrophy is caused by domino-like rearrangements in cellular
      retinaldehyde-binding protein mutant R234W.
AB  - Cellular retinaldehyde-binding protein (CRALBP) is essential for mammalian vision
      by routing 11-cis-retinoids for the conversion of photobleached opsin molecules
      into photosensitive visual pigments. The arginine-to-tryptophan missense mutation
      in position 234 (R234W) in the human gene RLBP1 encoding CRALBP compromises
      visual pigment regeneration and is associated with Bothnia dystrophy. Here we
      report the crystal structures of both wild-type human CRALBP and of its mutant
      R234W as binary complexes complemented with the endogenous ligand 11-cis-retinal,
      at 3.0 and 1.7 A resolution, respectively. Our structural model of wild-type
      CRALBP locates R234 to a positively charged cleft at a distance of 15 A from the
      hydrophobic core sequestering 11-cis-retinal. The R234W structural model reveals
      burial of W234 and loss of dianion-binding interactions within the cleft with
      physiological implications for membrane docking. The burial of W234 is
      accompanied by a cascade of side-chain flips that effect the intrusion of the
      side-chain of I238 into the ligand-binding cavity. As consequence of the
      intrusion, R234W displays 5-fold increased resistance to light-induced
      photoisomerization relative to wild-type CRALBP, indicating tighter binding to 11
      cis-retinal. Overall, our results reveal an unanticipated domino-like structural
      transition causing Bothnia-type retinal dystrophy by the impaired release of 11
      cis-retinal from R234W.

PMID- 19846786
TI  - T-tubule disorganization and defective excitation-contraction coupling in muscle
      fibers lacking myotubularin lipid phosphatase.
AB  - Skeletal muscle contraction is triggered by the excitation-contraction (E-C)
      coupling machinery residing at the triad, a membrane structure formed by the
      juxtaposition of T-tubules and sarcoplasmic reticulum (SR) cisternae. The
      formation and maintenance of this structure is key for muscle function but is not
      well characterized. We have investigated the mechanisms leading to X-linked
      myotubular myopathy (XLMTM), a severe congenital disorder due to loss of function
      mutations in the MTM1 gene, encoding myotubularin, a phosphoinositide phosphatase
      thought to have a role in plasma membrane homeostasis and endocytosis. Using a
      mouse model of the disease, we report that Mtm1-deficient muscle fibers have a
      decreased number of triads and abnormal longitudinally oriented T-tubules. In
      addition, SR Ca(2+) release elicited by voltage-clamp depolarizations is strongly
      depressed in myotubularin-deficient muscle fibers, with myoplasmic Ca(2+) removal
      and SR Ca(2+) content essentially unaffected. At the molecular level, Mtm1
      deficient myofibers exhibit a 3-fold reduction in type 1 ryanodine receptor
      (RyR1) protein level. These data reveal a critical role of myotubularin in the
      proper organization and function of the E-C coupling machinery and strongly
      suggest that defective RyR1-mediated SR Ca(2+) release is responsible for the
      failure of muscle function in myotubular myopathy.

PMID- 19846787
TI  - Role of cortical tension in bleb growth.
AB  - Blebs are spherical membrane protrusions often observed during cell migration,
      cell spreading, cytokinesis, and apoptosis, both in cultured cells and in vivo.
      Bleb expansion is thought to be driven by the contractile actomyosin cortex,
      which generates hydrostatic pressure in the cytoplasm and can thus drive
      herniations of the plasma membrane. However, the role of cortical tension in bleb
      formation has not been directly tested, and despite the importance of blebbing,
      little is known about the mechanisms of bleb growth. In order to explore the link
      between cortical tension and bleb expansion, we induced bleb formation on cells
      with different tensions. Blebs were nucleated in a controlled manner by laser
      ablation of the cortex, mimicking endogenous bleb nucleation. Cortical tension
      was modified by treatments affecting the level of myosin activity or proteins
      regulating actin turnover. We show that there is a critical tension below which
      blebs cannot expand. Above this threshold, the maximal size of a bleb strongly
      depends on tension, and this dependence can be fitted with a model of the cortex
      as an active elastic material. Together, our observations and model allow us to
      relate bleb shape parameters to the underlying cellular mechanics and provide
      insights as to how bleb formation can be biochemically regulated during cell
      motility.

PMID- 19846788
TI  - An early productive ocean unfit for aerobics.

PMID- 19846790
TI  - Size, shape, and the thermal niche of endotherms.
AB  - A key challenge in ecology is to define species' niches on the basis of
      functional traits. Size and shape are important determinants of a species' niche
      but their causal role is often difficult to interpret. For endotherms, size and
      shape define the thermal niche through their interaction with core temperature,
      insulation, and environmental conditions, determining the thermoneutral zone
      (TNZ) where energy and water costs are minimized. Laboratory measures of
      metabolic rate used to describe TNZs cannot be generalized to infer the capacity
      for terrestrial animals to find their TNZ in complex natural environments. Here,
      we derive an analytical model of the thermal niche of an ellipsoid furred
      endotherm that accurately predicts field and laboratory data. We use the model to
      illustrate the relative importance of size and shape on the location of the TNZ
      under different environmental conditions. The interaction between body shape and
      posture strongly influences the location of the TNZ and the expected scaling of
      metabolic rate with size at constant temperature. We demonstrate that the latter
      relationship has a slope of approximately (1/2) rather than the commonly expected
      surface area/volume scaling of (2/3). We show how such functional traits models
      can be integrated with spatial environmental datasets to calculate null
      expectations for body size clines from a thermal perspective, aiding mechanistic
      interpretation of empirical clines such as Bergmann's Rule. The combination of
      spatially explicit data with biophysical models of heat exchange provides a
      powerful means for studying the thermal niches of endotherms across climatic
      gradients.

PMID- 19846789
TI  - Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX
      770.
AB  - Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the gene
      encoding the CF transmembrane conductance regulator (CFTR), a protein kinase A
      (PKA)-activated epithelial anion channel involved in salt and fluid transport in
      multiple organs, including the lung. Most CF mutations either reduce the number
      of CFTR channels at the cell surface (e.g., synthesis or processing mutations) or
      impair channel function (e.g., gating or conductance mutations) or both. There
      are currently no approved therapies that target CFTR. Here we describe the in
      vitro pharmacology of VX-770, an orally bioavailable CFTR potentiator in clinical
      development for the treatment of CF. In recombinant cells VX-770 increased CFTR
      channel open probability (P(o)) in both the F508del processing mutation and the
      G551D gating mutation. VX-770 also increased Cl(-) secretion in cultured human CF
      bronchial epithelia (HBE) carrying the G551D gating mutation on one allele and
      the F508del processing mutation on the other allele by approximately 10-fold, to
      approximately 50% of that observed in HBE isolated from individuals without CF.
      Furthermore, VX-770 reduced excessive Na(+) and fluid absorption to prevent
      dehydration of the apical surface and increased cilia beating in these epithelial
      cultures. These results support the hypothesis that pharmacological agents that
      restore or increase CFTR function can rescue epithelial cell function in human CF
      airway.

PMID- 19846791
TI  - Insights into the reactivation of cobalamin-dependent methionine synthase.
AB  - Cobalamin-dependent methionine synthase (MetH) is a modular protein that
      catalyzes the transfer of a methyl group from methyltetrahydrofolate to
      homocysteine to produce methionine and tetrahydrofolate. The cobalamin cofactor,
      which serves as both acceptor and donor of the methyl group, is oxidized once
      every approximately 2,000 catalytic cycles and must be reactivated by the uptake
      of an electron from reduced flavodoxin and a methyl group from S-adenosyl-L
      methionine (AdoMet). Previous structures of a C-terminal fragment of MetH
      (MetH(CT)) revealed a reactivation conformation that juxtaposes the cobalamin-
      and AdoMet-binding domains. Here we describe 2 structures of a disulfide
      stabilized MetH(CT) ((s-s)MetH(CT)) that offer further insight into the
      reactivation of MetH. The structure of (s-s)MetH(CT) with cob(II)alamin and S
      adenosyl-L-homocysteine represents the enzyme in the reactivation step preceding
      electron transfer from flavodoxin. The structure supports earlier suggestions
      that the enzyme acts to lower the reduction potential of the Co(II)/Co(I) couple
      by elongating the bond between the cobalt and its upper axial water ligand,
      effectively making the cobalt 4-coordinate, and illuminates the role of Tyr-1139
      in the stabilization of this 4-coordinate state. The structure of (s-s)MetH(CT)
      with aquocobalamin may represent a transient state at the end of reactivation as
      the newly remethylated 5-coordinate methylcobalamin returns to the 6-coordinate
      state, triggering the rearrangement to a catalytic conformation.

PMID- 19846792
TI  - X-ray structure of Pur-alpha reveals a Whirly-like fold and an unusual nucleic
      acid binding surface.
AB  - The PUR protein family is a distinct and highly conserved class that is
      characterized by its sequence-specific RNA- and DNA-binding. Its best-studied
      family member, Pur-alpha, acts as a transcriptional regulator, as host factor for
      viral replication, and as cofactor for mRNP localization in dendrites. Pur-alpha
      deficient mice show severe neurologic defects and die after birth. Nucleic-acid
      binding by Pur-alpha is mediated by its central core region, for which no
      structural information is available. We determined the x-ray structure of
      residues 40 to 185 from Drosophila melanogaster Pur-alpha, which constitutes a
      major part of the core region. We found that this region contains two almost
      identical structural motifs, termed "PUR repeats," which interact with each other
      to form a PUR domain. DNA- and RNA-binding studies confirmed that PUR domains are
      indeed functional nucleic-acid binding domains. Database analysis show that PUR
      domains share a fold with the Whirly class of nucleic-acid binding proteins.
      Structural analysis combined with mutational studies suggest that a PUR domain
      binds nucleic acids through two independent surface regions involving concave
      beta-sheets. Structure-based sequence alignment revealed that the core region
      harbors a third PUR repeat at its C terminus. Subsequent characterization by
      small-angle x-ray scattering (SAXS) and size-exclusion chromatography indicated
      that PUR repeat III mediates dimerization of Pur-alpha. Surface envelopes
      calculated from SAXS data show that the Pur-alpha dimer consisting of repeats I
      to III is arranged in a Z-like shape. This unexpected domain organization of the
      entire core domain of Pur-alpha has direct implications for ssDNA/ssRNA and dsDNA
      binding.

PMID- 19846793
TI  - Glycemia and its relationship to outcomes in the metformin in gestational
      diabetes trial.
AB  - OBJECTIVE: To determine how glucose control in women with GDM treated with
      metformin and/or insulin influenced pregnancy outcomes. RESEARCH DESIGN AND
      METHODS: Women randomly assigned to metformin or insulin treatment in the
      Metformin in Gestational Diabetes (MiG) trial had baseline glucose tolerance test
      (OGTT) results and A1C documented, together with all capillary glucose
      measurements during treatment. In the 724 women who had glucose data for
      analysis, tertiles of baseline glucose values and A1C and of mean capillary
      glucose values during treatment were calculated. The relationships between
      maternal factors, glucose values, and outcomes (including a composite of neonatal
      complications, preeclampsia, and large-for-gestational-age [LGA] and small-for
      gestational-age infants) were examined with bivariable and multivariate models.
      RESULTS: Baseline OGTT did not predict outcomes, but A1C predicted LGA infants (P
      = 0.003). During treatment, fasting capillary glucose predicted neonatal
      complications (P < 0.001) and postprandial glucose predicted preeclampsia (P =
      0.016) and LGA infants (P = 0.001). Obesity did not influence outcomes, and there
      was no interaction between glycemic control, randomized treatment, or maternal
      BMI in predicting outcomes. The lowest risk of complications was seen when
      fasting capillary glucose was <4.9 mmol/l (mean +/- SD 4.6 +/- 0.3 mmol/l)
      compared with 4.9-5.3 mmol/l or higher and when 2-h postprandial glucose was 5.9
      6.4 mmol/l (6.2 +/- 0.2 mmol/l) or lower. CONCLUSIONS: Glucose control in women
      with gestational diabetes mellitus treated with metformin and/or insulin is
      strongly related to outcomes. Obesity is not related to outcomes in this group.
      Targets for fasting and postprandial capillary glucose may need to be lower than
      currently recommended.

PMID- 19846794
TI  - Glycated albumin and glycated hemoglobin are influenced differently by endogenous
      insulin secretion in patients with type 2 diabetes.
AB  - OBJECTIVE: Glycated albumin (GA) relative to A1C is a useful marker of short-term
      glycemic control. We investigated whether endogenous insulin secretion in type 2
      diabetes has different effects on GA and A1C levels. RESEARCH DESIGN AND METHODS:
      A1C, GA, and GA-to-A1C ratio were compared in 202 type 2 diabetic patients by
      type of treatment. Effect of beta-cell function determined by homeostasis model
      assessment (HOMA-%beta) on GA-to-A1C ratio was examined. In addition, GA-to-A1C
      ratio was compared between type 2 diabetic patients and 16 patients with type 1
      diabetes. RESULTS: In type 2 diabetic patients, GA-to-A1C ratio was significantly
      higher in those treated with insulin than in those treated with diet or oral
      hypoglycemic agents. HOMA-%beta showed a significant inverse correlation with GA
      to-A1C ratio. This ratio was higher in type 1 diabetic patients than in type 2
      diabetic patients. CONCLUSIONS: In diabetic patients with decreased insulin
      secretion, serum GA levels are higher relative to A1C.

PMID- 19846795
TI  - Breast-feeding modulates the influence of the peroxisome proliferator-activated
      receptor-gamma (PPARG2) Pro12Ala polymorphism on adiposity in adolescents: The
      Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional
      study.
AB  - OBJECTIVE: The peroxisome proliferator-activated receptor-gamma2 (PPARG2)
      Pro12Ala polymorphism has been associated with a higher BMI and a lower risk of
      type 2 diabetes in adulthood. The association between adiposity and PPARG
      variants can be influenced by environmental factors such as early growth, dietary
      fat, and (as recently shown) breast-feeding. The objectives of this study were to
      assess 1) the influence of the PPARG2 Pro12Ala polymorphism on adiposity markers
      in adolescents and 2) a possible modulating effect of breast-feeding on these
      associations. RESEARCH DESIGN AND METHODS: Data on breast-feeding duration, BMI,
      and genotypes for the Pro12Ala polymorphism were available for 945 adolescents
      (mean age 14.7 years). The breast-feeding duration was obtained from parental
      records. We measured weight, height, waist circumference, and six skinfold
      thicknesses. RESULTS: No significant associations between the Pro12Ala
      polymorphism and any of the above-mentioned anthropometric parameters were found.
      There were significant interactions between the PPARG2 Pro12Ala polymorphism and
      breast-feeding with regard to adiposity measurements (all adjusted P < 0.05).
      Indeed, in children who had not been breast-fed, Ala12 allele carriers had higher
      adiposity parameters (e.g., Delta BMI +1.88 kg/m(2), adjusted for age, sex, and
      center, P = 0.007) than Pro12Pro adolescents. In contrast, in breast-fed
      subjects, there was no significant difference between Ala12 allele carriers and
      Pro12Pro children in terms of adiposity measurements, whatever the duration of
      breast-feeding. CONCLUSIONS: Breast-feeding appears to counter the deleterious
      effect of the PPARG2 Pro12Ala polymorphism on anthropometric parameters in
      adolescents.

PMID- 19846796
TI  - Closed-loop insulin delivery using a subcutaneous glucose sensor and
      intraperitoneal insulin delivery: feasibility study testing a new model for the
      artificial pancreas.
AB  - OBJECTIVE: Attempts to build an artificial pancreas by using subcutaneous insulin
      delivery from a portable pump guided by an subcutaneous glucose sensor have
      encountered delays and variability of insulin absorption. We tested closed-loop
      intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous
      glucose sensor via a proportional-integral-derivative (PID) algorithm. RESEARCH
      DESIGN AND METHODS: Two-day closed-loop therapy (except for a 15-min pre-meal
      manual bolus) was compared with a 1-day control phase with intraperitoneal open
      loop insulin delivery, according to randomized order, in a hospital setting in
      eight type 1 diabetic patients treated by implanted pumps. The percentage of time
      spent with blood glucose in the 4.4-6.6 mmol/l range was the primary end point.
      RESULTS During the closed-loop phases, the mean +/- SEM percentage of time spent
      with blood glucose in the 4.4-6.6 mmol/l range was significantly higher (39.1 +/-
      4.5 vs. 27.7 +/- 6.2%, P = 0.05), and overall dispersion of blood glucose values
      was reduced among patients. Better closed-loop glucose control came from the time
      periods excluding the two early postprandial hours with a higher percentage of
      time in the 4.4-6.6 mmol/l range (46.3 +/- 5.3 vs. 28.6 +/- 7.4, P = 0.025) and
      lower mean blood glucose levels (6.9 +/- 0.3 vs. 7.9 +/- 0.6 mmol/l, P = 0.036).
      Time spent with blood glucose <3.3 mmol/l was low and similar for both
      investigational phases. CONCLUSIONS: Our results demonstrate the feasibility of
      intraperitoneal insulin delivery for an artificial beta-cell and support the need
      for further study. Moreover, according to a semiautomated mode, the features of
      the pre-meal bolus in terms of timing and amount warrant further research.

PMID- 19846797
TI  - Association of metformin, elevated homocysteine, and methylmalonic acid levels
      and clinically worsened diabetic peripheral neuropathy.
AB  - OBJECTIVE: The severity of peripheral neuropathy in diabetic patients varies for
      unclear reasons. Long-term use of metformin is associated with malabsorption of
      vitamin B(12) (cobalamin [Cbl]) and elevated homocysteine (Hcy) and methylmalonic
      acid (MMA) levels, which may have deleterious effects on peripheral nerves. The
      intent of this study was to clarify the relationship among metformin exposure,
      levels of Cbl, Hcy, and MMA, and severity of peripheral neuropathy in diabetic
      patients. We hypothesized that metformin exposure would be associated with lower
      Cbl levels, elevated Hcy and MMA levels, and more severe peripheral neuropathy.
      RESEARCH DESIGN AND METHODS: This was a prospective case-control study of
      patients with type 2 diabetes and concurrent symptomatic peripheral neuropathy,
      comparing those who had received >6 months of metformin therapy (n = 59) with
      those without metformin exposure (n = 63). Comparisons were made using clinical
      (Toronto Clinical Scoring System and Neuropathy Impairment Score), laboratory
      (serum Cbl, fasting Hcy, and fasting MMA), and electrophysiological measures
      (nerve conduction studies). RESULTS: Metformin-treated patients had depressed Cbl
      levels and elevated fasting MMA and Hcy levels. Clinical and electrophysiological
      measures identified more severe peripheral neuropathy in these patients; the
      cumulative metformin dose correlated strongly with these clinical and
      paraclinical group differences. CONCLUSIONS: Metformin exposure may be an
      iatrogenic cause for exacerbation of peripheral neuropathy in patients with type
      2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should
      be considered upon initiation of, as well as during, metformin therapy to detect
      potential secondary causes of worsening peripheral neuropathy.

PMID- 19846798
TI  - Effects of long-term fenofibrate treatment on markers of renal function in type 2
      diabetes: the FIELD Helsinki substudy.
AB  - OBJECTIVE: Although fenofibrate was associated with less progression of
      albuminuria in the Fenofibrate Intervention and Event Lowering in Diabetes
      (FIELD) study, it is unknown if it has any effect on renal function. We explored
      if there were changes in commonly available markers of renal function during
      fenofibrate treatment in the FIELD Helsinki cohort excluding statin users.
      RESEARCH DESIGN AND METHODS: One hundred and seventy subjects with type 2
      diabetes were randomly assigned to micronized fenofibrate (200 mg/day) or placebo
      for 5 years. In this substudy, we measured several markers of albumin excretion
      and renal function. RESULTS: After intensified treatment, blood pressure and
      fasting glucose decreased in both groups while A1C remained at 7.2%. Plasma
      creatinine increased with fenofibrate while urine creatinine remained comparable
      between the groups, resulting in significant decreases in both creatinine
      clearance and estimated glomerular filtration rate (eGFR) by the Modification of
      Diet in Renal Disease (MDRD)-4 and Cockroft-Gault equations in the fenofibrate
      group. Cystatin C increased during fenofibrate treatment. Urinary albumin-to
      creatinine ratio and diurnal urine protein remained unchanged, whereas overnight
      urinary albumin excretion rate showed minor decreases in both groups.
      CONCLUSIONS: We report concomitant decreases in creatinine clearance and eGFR by
      fenofibrate. These changes complicate the clinical surveillance during
      fenofibrate treatment. We could not demonstrate the beneficial effects of
      fenofibrate on albumin excretion. A novel finding is the increase of cystatin C
      in type 2 diabetic patients during fenofibrate treatment. The clinical relevance
      of the changes needs to be assessed in a long-term outcome study of renal
      function.

PMID- 19846799
TI  - Associations of serum concentrations of 25-hydroxyvitamin D and parathyroid
      hormone with surrogate markers of insulin resistance among U.S. adults without
      physician-diagnosed diabetes: NHANES, 2003-2006.
AB  - OBJECTIVE: To examine whether concentrations of serum 25-hydroxyvitamin D
      (25[OH]D) and parathyroid hormone (PTH) are associated with surrogate markers of
      insulin resistance (IR) in U.S. adults without physician-diagnosed diabetes.
      RESEARCH DESIGN AND METHODS: Cross-sectional data (n = 3,206) from the National
      Health and Nutrition Examination Survey (NHANES) 2003-2006 were analyzed.
      RESULTS: The age-adjusted prevalence of hyperinsulinemia, high homeostasis model
      assessment-IR, high GHb, and fasting and 2-h hyperglycemia decreased linearly
      across quintiles of 25(OH)D but increased linearly across quintiles of PTH
      (except for a quadratic trend for fasting hyperglycemia). After extensive
      adjustment for potential confounders, the relationships between 25(OH)D and the
      markers of IR and 2-h hyperglycemia persisted. Only hyperinsulinemia was
      positively associated with PTH (P < 0.05). CONCLUSIONS: Among U.S. adults without
      physician-diagnosed diabetes, low concentrations of serum 25(OH)D were associated
      with markers of IR. The role of PTH in IR deserves further investigation.

PMID- 19846800
TI  - Microalbuminuria, preeclampsia, and preterm delivery in pregnant women with type
      1 diabetes: results from a nationwide Danish study.
AB  - OBJECTIVE: To study the association between microalbuminuria and development of
      preeclampsia and preterm delivery in pregnant women with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: This was a population-based prospective study in 846
      normoalbuminuric or microalbuminuric women with type 1 diabetes without
      antihypertensive treatment in early pregnancy. Data were collected prospectively
      by one to three caregivers in each center and reported to a central registry.
      RESULTS: The prevalence of microalbuminuria in the first trimester was 10%,
      median diabetes duration was 11 years, and third-trimester A1C was 6.6%. The
      frequencies of preeclampsia and preterm delivery before 34 weeks in the
      microalbuminuric group were 40 and 13%, both significantly higher than those in
      the normoalbuminuric group (12 and 6%, respectively, P < 0.001). After
      adjustments for possible confounders, significant predictors for development of
      preeclampsia were microalbuminuria (odds ratio 4.0 [95% CI]), nulliparity (3.1
      [1.9-5.1]), and third-trimester A1C (1.3 [1.1-1.5] per 1% increase). Delivery
      before 34 weeks was associated with early microalbuminuria in univariate
      analyses, but in multivariate analyses A1C was the only significant predictor of
      this outcome. Preeclampsia was associated with a threefold higher risk of
      delivery before 34 weeks. CONCLUSIONS: The presence of microalbuminuria in early
      pregnancy is associated with a fourfold increased risk of developing
      preeclampsia. A1C values during pregnancy are highly predictive of both
      preeclampsia and preterm delivery. Future research with antihypertensive
      treatment in normotensive, microalbuminuric pregnant women to prevent
      preeclampsia is proposed.

PMID- 19846801
TI  - Insulin causes hyperthermia by direct inhibition of warm-sensitive neurons.
AB  - OBJECTIVE: Temperature and nutrient homeostasis are two interdependent components
      of energy balance regulated by distinct sets of hypothalamic neurons. The
      objective is to examine the role of the metabolic signal insulin in the control
      of core body temperature (CBT). RESEARCH DESIGN AND METHODS: The effect of
      preoptic area administration of insulin on CBT in mice was measured by
      radiotelemetry and respiratory exchange ratio. In vivo 2-[(18)F]fluoro-2
      deoxyglucose uptake into brown adipose tissue (BAT) was measured in rats after
      insulin treatment by positron emission tomography combined with X-ray computed
      tomography imaging. Insulin receptor-positive neurons were identified by
      retrograde tracing from the raphe pallidus. Insulin was locally applied on
      hypothalamic slices to determine the direct effects of insulin on intrinsically
      warm-sensitive neurons by inducing hyperpolarization and reducing firing rates.
      RESULTS: Injection of insulin into the preoptic area of the hypothalamus induced
      a specific and dose-dependent elevation of CBT mediated by stimulation of BAT
      thermogenesis as shown by imaging and respiratory ratio measurements. Retrograde
      tracing indicates that insulin receptor-expressing warm-sensitive neurons
      activate BAT through projection via the raphe pallidus. Insulin applied on
      hypothalamic slices acted directly on intrinsically warm-sensitive neurons by
      inducing hyperpolarization and reducing firing rates. The hyperthermic effects of
      insulin were blocked by pretreatment with antibodies to insulin or with a
      phosphatidylinositol 3-kinase inhibitor. CONCLUSIONS: Our findings demonstrate
      that insulin can directly modulate hypothalamic neurons that regulate
      thermogenesis and CBT and indicate that insulin plays an important role in
      coupling metabolism and thermoregulation at the level of anterior hypothalamus.

PMID- 19846802
TI  - Adipocyte turnover: relevance to human adipose tissue morphology.
AB  - OBJECTIVE: Adipose tissue may contain few large adipocytes (hypertrophy) or many
      small adipocytes (hyperplasia). We investigated factors of putative importance
      for adipose tissue morphology. RESEARCH DESIGN AND METHODS: Subcutaneous
      adipocyte size and total fat mass were compared in 764 subjects with BMI 18-60
      kg/m(2). A morphology value was defined as the difference between the measured
      adipocyte volume and the expected volume given by a curved-line fit for a given
      body fat mass and was related to insulin values. In 35 subjects, in vivo
      adipocyte turnover was measured by exploiting incorporation of atmospheric (14)C
      into DNA. RESULTS: Occurrence of hyperplasia (negative morphology value) or
      hypertrophy (positive morphology value) was independent of sex and body weight
      but correlated with fasting plasma insulin levels and insulin sensitivity,
      independent of adipocyte volume (beta-coefficient = 0.3, P < 0.0001). Total
      adipocyte number and morphology were negatively related (r = -0.66); i.e., the
      total adipocyte number was greatest in pronounced hyperplasia and smallest in
      pronounced hypertrophy. The absolute number of new adipocytes generated each year
      was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual
      values for adipocyte generation and morphology were strongly related (r = 0.7, P
      < 0.001). The relative death rate (approximately 10% per year) or mean age of
      adipocytes (approximately 10 years) was not correlated with morphology.
      CONCLUSIONS: Adipose tissue morphology correlates with insulin measures and is
      linked to the total adipocyte number independently of sex and body fat level. Low
      generation rates of adipocytes associate with adipose tissue hypertrophy, whereas
      high generation rates associate with adipose hyperplasia.

PMID- 19846803
TI  - Chronic maternal dietary chromium restriction modulates visceral adiposity:
      probable underlying mechanisms.
AB  - OBJECTIVE: We demonstrated previously that chronic maternal micronutrient
      restriction altered the body composition in rat offspring and may predispose
      offspring to adult-onset diseases. Chromium (Cr) regulates glucose and fat
      metabolism. The objective of this study is to determine the long-term effects of
      maternal Cr restriction on adipose tissue development and function in a rat
      model. RESEARCH DESIGN AND METHODS: Female weanling WNIN rats received, ad
      libitum, a control diet or the same with 65% restriction of Cr (CrR) for 3 months
      and mated with control males. Some pregnant CrR mothers were rehabilitated from
      conception or parturition and their pups weaned to control diet. Whereas some CrR
      offspring were weaned to control diet, others continued on CrR diet. Various
      parameters were monitored in the offspring at three monthly intervals up to 15-18
      months of age. RESULTS: Maternal Cr restriction significantly increased body
      weight and fat percentage, especially the central adiposity in both male and
      female offspring. Further, the expression of leptin and 11 beta-hydroxysteroid
      dehydrogenase 1 genes were significantly increased in CrR offspring of both the
      sexes. Adipocytokine levels were altered in plasma and adipose tissue;
      circulating triglyceride and FFA levels were increased, albeit in female
      offspring only. Rehabilitation regimes did not correct body adiposity but
      restored the circulating levels of lipids and adipocytokines. CONCLUSIONS:
      Chronic maternal Cr restriction increased body adiposity probably due to
      increased stress and altered lipid metabolism in WNIN rat offspring, which may
      predispose them to obesity and associated diseases in later life.

PMID- 19846804
TI  - Thyroid cytology comes to Bethesda.

PMID- 19846805
TI  - The Bethesda System For Reporting Thyroid Cytopathology.
AB  - To address terminology and other issues related to thyroid fine-needle aspiration
      (FNA), the National Cancer Institute (NCI) hosted the NCI Thyroid FNA State of
      the Science Conference. The conclusions regarding terminology and morphologic
      criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form
      the framework for The Bethesda System for Reporting Thyroid Cytopathology
      (TBSRTC). For clarity of communication, TBSRTC recommends that each report begin
      with 1 of 6 general diagnostic categories. The project participants hope that the
      adoption of this flexible framework will facilitate communication among
      cytopathologists, endocrinologists, surgeons, radiologists, and other health care
      providers; facilitate cytologic-histologic correlation for thyroid diseases;
      facilitate research into the epidemiology, molecular biology, pathology, and
      diagnosis of thyroid diseases; and allow easy and reliable sharing of data from
      different laboratories for national and international collaborative studies.

PMID- 19846806
TI  - Epidemiology and susceptibilities of methicillin-resistant Staphylococcus aureus
      in Northeastern Ohio.
AB  - A retrospective survey was performed on all staphylococcal infections diagnosed
      by the Ashtabula County Medical Center (Ashtabula, OH) during 2006 and 2007. Of
      the 1,612 Staphylococcus aureus isolates evaluated for their antibiotic
      resistances, 947 were methicillin-resistant S aureus (MRSA). In 2007, MRSA
      infections reached 589 cases per 100,000 inhabitants, a 77% increase compared
      with 2006. The increase in MRSA infections was noticeable among youth (6-25 years
      old), middle-aged people (45-50 years old), and elderly people (86-90 years old).
      MRSA infections increased among inpatients by 58%, among outpatients by 43%, and
      among nursing home residents by 183%. More than 66% of MRSA infections were found
      among healthy people in the community with no apparent risk factors. More than
      88.7% of the infections belong to only 9 profiles of antibiotic resistance
      indiscriminately distributed among inpatients, outpatients, and nursing home
      residents. This report sheds further light on the rapid spread of MRSA across
      Northeastern Ohio, stressing the need for better education in preventive measures
      and infection control at the level of community and health care settings.

PMID- 19846807
TI  - Is the QuantiFERON-TB blood assay a good replacement for the tuberculin skin test
      in tuberculosis screening? a pilot study at Berkshire Medical Center.
AB  - The QuantiFERON-TB Gold In-Tube method (QFT-GIT; Cellestis, Carnegie, Australia)
      is a recently US Food and Drug Administration-approved interferon-gamma release
      assay (IGRA) for the detection of tuberculosis infection, which has been screened
      for by the tuberculin skin test (TST) for nearly a century. We report a pilot
      study comparing the QFT-GIT and TST results for screening health care workers
      (HCWs) at Berkshire Medical Center (BMC; Pittsfield, MA), the second hospital in
      Massachusetts to use QFT-GIT. For the study, 40 BMC HCWs, 20 TST+ and 20 TST-,
      were screened with the QFT-GIT test. All 20 TST- subjects were also QFT-GIT-,
      while only 10 of 20 TST+ subjects were QFT-GIT+. The overall agreement between
      the QFT-GIT and TST results was 75% (kappa = 0.5; 95% confidence interval, 0.268
      0.732). The suboptimal agreement was partially due to a higher specificity of QFT
      GIT. Confounding factors (eg, bacille Calmette-Guerin vaccination status and
      birthplace) are discussed, and literature regarding IGRAs and their comparison
      with TST is reviewed.

PMID- 19846808
TI  - Relative quantity of cerebrospinal fluid herpes simplex virus DNA in adult cases
      of encephalitis and meningitis.
AB  - Herpes simplex virus (HSV) remains an important cause of meningitis and
      encephalitis in adults, and polymerase chain reaction (PCR)-based tests are the
      "gold standard" for diagnosis. The objective of this study was to assess
      differences in semiquantitative PCR values, based on the crossing threshold (Ct)
      value for cases of HSV meningitis and encephalitis. A retrospective chart review
      was performed for 29 patients with a documented diagnosis of HSV meningitis or
      encephalitis during the course of 5 years from a large urban academic hospital.
      Demographic information, cerebrospinal fluid (CSF) laboratory findings, and PCR
      data were obtained for each patient. There was no statistically significant
      difference in the Ct values in patients with meningitis or encephalitis. In
      addition, no differences were found in CSF chemistry and hematology parameters.
      There is a broad range in relative concentrations of HSV DNA in the CSF in cases
      of meningitis and encephalitis.

PMID- 19846809
TI  - Aberrant underexpression of CD81 in precursor B-cell acute lymphoblastic
      leukemia: utility in detection of minimal residual disease by flow cytometry.
AB  - We studied CD81 expression by flow cytometry (FC) on benign precursor B cells
      (hematogones) and leukemic blasts in precursor B-cell acute lymphoblastic
      leukemia (pre-B-ALL) and established its usefulness in minimal residual disease
      (MRD) assays. Hematogones showed uniformly bright CD81 expression. In 98 pre-B
      ALLs at diagnosis or overt relapse, 80 (82%) showed aberrantly decreased CD81
      intensity. We used hematogones in 139 MRD- specimens to set a lower threshold for
      normal CD81 expression. In 133 specimens positive for residual pre-B-ALL, 87.2%
      showed increased CD81-dim immature B cells (>10%) and/or a discrete cluster of
      CD81-dim cells in a background of hematogones. Only 1 of 139 MRD- specimens
      showed more than 10% CD81-dim cells. Decreased CD81 expression was maintained in
      91% of aberrant cases analyzed before and after chemotherapy. Decreased CD81
      expression is a sensitive and specific marker for residual pre-B-ALL, even in a
      background of hematogones, making CD81 a useful addition to a panel for MRD
      detection by FC.

PMID- 19846810
TI  - Immunophenotypic variations in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) expresses pan-B-cell antigens and is usually CD5+/CD10
      /CD23-/FMC7+. In this study, we evaluated 52 patients with confirmed diagnoses of
      MCL and identified variant immunophenotypes in 21 patients (19/48 classical and
      2/4 variant MCLs), including CD5- in 6 (12%) of 52, CD10+ in 4 (8%) of 50, CD23+
      in 10 (21%) of 48, and FMC7- in 4 (11%) of 37 cases. Three cases showed
      variations in 2 antigens, including CD5-/CD23+, CD10+/FMC7-, and CD23+/FMC7-;
      they were all classical MCLs. One blastoid variant MCL was CD23+, and one was
      FMC7-. Evaluation for proliferation index by immunohistochemical analysis for Ki
      67 demonstrated no significant difference between MCLs with variant
      immunophenotypes and MCLs with typical immunophenotypes. The high proliferation
      index (>60%) was exclusively seen in the blastoid and pleomorphic variants. Our
      results indicate that immunophenotypic variations are common in MCL, and
      recognizing the variability is important for accurate subclassification of B-cell
      lymphoma.

PMID- 19846811
TI  - Lymphocyte-depleted thymic remnants: a potential diagnostic pitfall in the
      evaluation of central neck dissections.
AB  - The head and neck region is a frequent site for potentially confusing incidental
      benign findings not related to the primary pathologic process and having no
      impact on patient prognosis. Several lesions are thymic in origin. We report 3
      cases of lymphocyte-poor thymic remnants identified in central cervical (level
      VI) lymph node dissections for unrelated benign and malignant pathology. In each,
      the rests were nearly completely composed of bland epithelial cells with rare
      admixed lymphocytes. These cells were immunophenotypically similar to thymic
      epithelial cells, although they differed in the paucity of associated thymic
      lymphocytes and lack of Hassall corpuscles. Lymphocyte-depleted thymic remnants
      in the central cervical compartment are not well described in the literature. It
      is important to be aware of these and other benign inclusions to avoid making
      incorrect diagnoses of malignancy.

PMID- 19846812
TI  - Clinical performance of JAK2 V617F mutation detection assays in a molecular
      diagnostics laboratory: evaluation of screening and quantitation methods.
AB  - The presence of the JAK2 V617F mutation is now part of clinical diagnostic
      algorithms, and JAK2 status is routinely assessed when BCR/ABL- chronic
      myeloproliferative neoplasms (MPNs) are suspected. The aim of this study was to
      evaluate performance of 3 screening and 1 quantitative method for JAK2 V617F
      detection. For the study, 43 samples (27 bone marrow aspirates and 16 peripheral
      blood samples) were selected. The screening assays were the JAK2 Activating
      Mutation Assay (InVivoScribe, San Diego, CA), JAK2 MutaScreen kit (Ipsogen,
      Luminy Biotech, Marseille, France), and a home-brew melting curve analysis
      method. Ipsogen's JAK2 MutaQuant assay was used for quantification of mutant and
      wild-type alleles. The limit of detection was 1% for the kit-based screening
      methods and 10% for the melting curve method. The JAK2 MutaQuant assay
      demonstrated analytic sensitivity of 0.01%. All 4 methods detected cases of
      BCR/ABL- MPNs and gave negative results with BCR/ABL+ chronic myelogenous
      leukemia, multiple myeloma, myelodysplastic syndrome, and normal cases.

PMID- 19846813
TI  - T-cell receptor gene rearrangement and CD30 immunoreactivity in traumatic
      ulcerative granuloma with stromal eosinophilia of the oral cavity.
AB  - Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is an ulcerative
      lesion of the oral mucosa with unknown pathogenesis. A few recent case reports
      have demonstrated molecular evidence of T-cell clonality in TUGSE and CD30
      immunoreactivity in the large atypical mononuclear cells, raising the possibility
      that a TUGSE subset may represent the oral counterpart of primary cutaneous CD30+
      T-cell lymphoproliferative disorders. We examined the immunoreactivity for CD30
      and T-cell receptor (TCR) gamma gene rearrangement in 37 TUGSE cases. Clonal TCR
      gene rearrangements were demonstrated in 7 (24%) of 29 cases with amplifiable
      DNA, and the morphologic features and CD30 immunoreactivity of these cases did
      not differ from those with polyclonal TCR gene rearrangements. Clinical follow-up
      was available for 5 of 7 TUGSE cases with clonal TCR gene rearrangement for an
      average period of 1.75 years after the initial biopsy or excision, and there was
      no evidence of local recurrence or development of systemic T-cell
      lymphoproliferative disorder. Without morphologic and/or clinical evidence of
      lymphoma, T-cell clonality and/or CD30 positivity in these lesions is not
      indicative of malignancy and should be interpreted with caution.

PMID- 19846814
TI  - Flow cytometric immunophenotyping and minimal residual disease analysis in
      multiple myeloma.
AB  - Presence of normal plasma cells (PCs), hemodilution of bone marrow aspirate, and
      changes in the immunophenotype are important considerations in minimal residual
      disease (MRD) assessment in multiple myeloma (MM). We evaluated 124 subjects-107
      with MM, 11 with Hodgkin lymphoma, and 6 allogeneic stem cell transplantation
      donors-for the immunophenotype of neoplastic, reactive, and normal PCs
      respectively. Of the patients with MM, 36 were evaluated for MRD and 23 for a
      change in immunophenotype after chemotherapy. The immunophenotype of normal and
      reactive PCs was similar and differed from that of neoplastic PCs with respect to
      CD19, CD45, CD56, CD52, CD20, and CD117. At least 2 antigens were aberrantly
      expressed in all cases and 3 in 90.7% of MM cases. A change in the immunoprofile
      of PCs was observed in 18 (78%) of 23 cases. By using flow cytometry, we detected
      MRD in all samples, and a neoplastic PC index (percentage of neoplastic PCs/total
      bone marrow PCs) of less than 30 could differentiate immunofixation (IFx)- from
      IFx+ samples (complete and partial responders, respectively).

PMID- 19846815
TI  - Significant CD5 expression on normal stage 3 hematogones and mature B Lymphocytes
      in bone marrow.
AB  - B-cell maturation from hematogones to mature B cells in bone marrow exhibits a
      consistent, complex spectrum of sequential antigen expression. CD5 expression,
      however, has not been characterized. We studied the dynamics of CD5 expression on
      developing B cells by 4-color flow cytometry in 32 patients, aged 9 months to 63
      years, with hematogone hyperplasia (>3.5% of total events). The mean percentage
      of hematogones was 8.1%. We demonstrate consistent CD5 expression on normal,
      polytypic B cells in a continuum, predominantly at later stages of maturation,
      specifically on stage 3 hematogones and mature B cells. Awareness of this normal
      pattern of CD5 expression on B-cell subsets has implications in the analysis of
      minimal residual disease of CD5+ B-lineage non-Hodgkin lymphomas.

PMID- 19846816
TI  - Fine-needle aspiration biopsy of chondromyxoid fibroma: an investigation of four
      cases.
AB  - We describe the cytologic features of chondromyxoid fibroma in fine-needle
      aspiration biopsy specimens in 4 patients. We analyzed rapid Romanowsky- and
      Papanicolaou-stained slides with a respect to overall cellularity, the presence
      of hypercellular chondromyxoid fragments (HCFs), nuclear atypia, cytoplasmic
      features, and the presence of giant cells. The most consistent and diagnostically
      useful feature was the presence of HCFs, which were present in all 4 cases. Mild
      to moderate nuclear atypia was additionally present in all 4 cases. Most cases
      were hypocellular (3/4). Giant cells were present in 2 cases, with 1 case
      exhibiting a hypercellular smear with numerous giant cells. All 4 cases were
      confirmed in subsequent histologic biopsy material. Strict attention to clinical,
      radiographic, and cytologic features, especially the presence of HCFs, can aid in
      the specific diagnosis of chondromyxoid fibroma on FNAB.

PMID- 19846817
TI  - Time trends in fungal infections as a cause of death in hematopoietic stem cell
      transplant recipients: an autopsy study.
AB  - Infectious complications remain an important cause of death in hematopoietic stem
      cell transplant (HSCT) recipients. We undertook a 20-year (1988-2007)
      retrospective review of all autopsies performed on HSCT recipients in our
      institution, with emphasis on infections, especially fungal infections, as the
      cause of death. Of the 2,943 autopsies performed in our institution from 1988 to
      2007, 395 (13.4%) involved HSCT recipients (117 pediatric; 278 adult). Of the
      patients, 298 had received allogeneic, 46 autologous, 41 umbilical cord blood,
      and 3 autologous plus allogeneic types, and 7 were unknown HSCT types. The most
      common causes of death were pulmonary complications, occurring in 247 (62.5%) of
      395 cases. In 178 cases (45.1%), microorganisms (viral, bacterial, and/or fungal)
      were documented at autopsy in one or more organs and contributed to the cause of
      death. Fungal infections were found in 23.5% of cases, but their frequency as a
      cause of death decreased throughout this study, from 30.3% in the 1988-1992
      period to 10.9% in the 2003-2007 period.

PMID- 19846818
TI  - Evaluation of cell surface expression of phosphatidylserine in ovarian carcinoma
      effusions using the annexin-V/7-AAD assay: clinical relevance and comparison with
      other apoptosis parameters.
AB  - Phosphatidylserine cell surface exposure during apoptosis can be detected by its
      binding to the protein annexin-V. We investigated annexin-V expression in 76
      ovarian carcinoma effusions using flow cytometry. Results were analyzed for
      association with clinicopathologic parameters and survival. Annexin-V expression
      was additionally compared with the previously studied apoptotic markers cleaved
      caspase-3, cleaved caspase-8, and deoxyuridine triphosphate (dUTP) incorporation
      into DNA fragments. Annexin-V was expressed in all specimens and was more
      frequently detected compared with cleaved caspases and dUTP incorporation (P <
      .001). Annexin-V expression was higher in grade 3 vs grades 1 and 2 tumors (P =
      .014). A higher percentage of annexin-V-expressing cells in postchemotherapy
      specimens was associated with poor overall (P = .005) and progression-free (P =
      .013) survival. We present the first evidence of annexin-V expression in ovarian
      carcinoma effusions. The higher annexin-V expression compared with other
      apoptosis parameters and its association with high-grade disease and poor
      survival in postchemotherapy patients suggest a role in cell survival rather than
      apoptosis in effusions.

PMID- 19846819
TI  - Should pathologists send all or only selected slides for patient-requested
      interlaboratory second opinion?
AB  - For interlaboratory second opinions requested by patients or clinicians, whether
      all or selected slides should be sent is unknown. We compared the disagreement
      rate for requested second opinions for 4 years of sending selected slides with
      the rate for 1 year of sending all slides. Disagreements were identified in 81
      (13.6%) of 596 cases (468 selected slides, 128 all slides). The disagreement rate
      was less when sending selected slides (n = 58 [12%]) vs all slides (n = 23 [18%];
      P = .03). Only 5 cases were identified with disagreement related to whether all
      or selected slides were sent (selected slides, 1 case [slide of interest
      inadvertently not chosen]; all slides, 4 cases; P = .03). When all slides were
      sent (disagreement in number of positive nodes, 2 cases; failure of second
      laboratory to identify microinvasive ductal carcinoma when present in 1 of 10
      core biopsy slides, and ductal carcinoma in situ [DCIS] adjacent to invasive
      ductal carcinoma when DCIS present on only 1 of 5 slides [2/81 (2%)], 1 case
      each). Sending all slides is associated with a higher disagreement rate than
      sending only selected slides, but this disagreement comes from correcting and
      introducing error.

PMID- 19846820
TI  - The Becton Dickinson FocalPoint GS Imaging System: clinical trials demonstrate
      significantly improved sensitivity for the detection of important cervical
      lesions.
AB  - Location-guided screening in cervical cytology offers a potentially significant
      advance over routine manual screening. A prospective, 2-armed, masked clinical
      trial of the BD FocalPoint GS Imaging System using SurePath slides (BD
      Diagnostics-TriPath, Burlington, NC) compared routine manual screening and
      quality control rescreening with computer-assisted, field-of-view screening and
      device-directed quality control rescreening. The results obtained in the 2 arms
      were compared with adjudicated reference diagnoses for each slide. Sensitivity,
      specificity, and negative predictive value were calculated for the detection of
      atypical squamous cells of undetermined significance and greater (ASC-US+), low
      grade squamous intraepithelial lesion and greater (LSIL+), and high-grade
      squamous intraepithelial lesion and greater (HSIL+) groups. We evaluated 12,313
      slides. The detection sensitivities for HSIL+ were increased by 19.6% (P < .0001)
      and for LSIL+ were increased by 9.8% (P < .0001) in the computer-assisted arm,
      with small statistically significant decreases in specificity. For ASC-US+
      sensitivity and specificity, the study arms were not statistically different. Use
      of this system might be expected to improve accuracy for clinically important
      entities without increasing equivocal case detection.

PMID- 19846822
TI  - Accuracy of urine cytology and the significance of an atypical category.
AB  - The "atypical urothelial cell" cytologic category is nonstandardized. We
      subclassify atypical cases to "atypical, favor a reactive process" or "atypical,
      unclear if reactive or neoplastic." We evaluated the predictive significance of
      atypical cases by looking at their histologic follow-up. Among the 1,114 patients
      and 3,261 specimens included, 282 specimens had histologic follow-up. An atypical
      diagnosis did not carry a significant increased risk of urothelial neoplasia
      compared with the benign category. Although an "atypical unclear" diagnosis
      carried a higher rate of detection of high-grade cancer on follow-up biopsy in
      comparison with "atypical reactive" or "negative" diagnoses (26/58 [45%] vs 15/52
      [29%] and 16/103 [15.5%], respectively), this difference was not statistically
      significant. These results suggest that dividing atypical cases into 2 categories
      based on the level of cytologic suspicion of cancer does not add clinically
      relevant information within the atypical category. They also raise the question
      of the significance of the atypical category altogether.

PMID- 19846821
TI  - p16(INK4a) expression analysis as an ancillary tool for cytologic diagnosis of
      urothelial carcinoma.
AB  - We immunochemically studied p16(INK4a) expression in 116 urine cytologic samples
      and compared results with 190 histologic samples. The cytologic samples were
      classified into 4 groups: 1, mild cellular atypia; 2, moderate cellular atypia;
      3, severe cellular atypia; and 4, malignancy. Overexpression of p16(INK4a) was
      detected in none of 32 cases in group 1, 8 (16%) of 50 cases in group 2, 5 (42%)
      of 12 cases in group 3, and 11 (50%) of 22 cases in group 4. In addition, by
      histologic analysis, p16(INK4a) overexpression was not detected in nonneoplastic
      urothelium, except for a few cases of reactive atypia, but it was detected in
      about 50% of urothelial carcinomas. In particular, a high incidence (16/20 [80%])
      of p16(INK4a) overexpression in high-grade carcinomas was noted in cytologic
      samples. Immunocytologic analysis of p16(INK4a) expression in cytologic samples
      is a useful ancillary tool for detection of urothelial carcinoma with
      infiltrating potential.

PMID- 19846823
TI  - Embolization of hydrophilic catheter coating to the lungs: report of a case
      mimicking granulomatous vasculitis.
AB  - Hydrophilic coatings are used on intravascular devices to facilitate ease of
      manipulation and to minimize complications such as thrombosis during a procedure
      and vasospasm after a procedure. We report a case of embolization of hydrophilic
      coating of a central venous catheter to the lung that resulted in cavitary lung
      nodules in a 34-year-old woman. The microscopic features of this unusual
      complication warrant emphasis so that pathologists will not overlook the embolic
      foreign material and make a faulty diagnosis of noniatrogenic granulomatous
      vasculitis.

PMID- 19846825
TI  - Assessment of platelet function in whole blood by multiple electrode
      aggregometry: transport of samples using a pneumatic tube system.

PMID- 19846826
TI  - Measuring of ESR with test 1 is more useful than the Westergren method in
      rheumatoid arthritis.

PMID- 19846827
TI  - On the meaning of the erythrocyte sedimentation rate.

PMID- 19846828
TI  - Age, Alzheimer disease, and brain structure.
AB  - BACKGROUND: Lack of clear understanding remains on the overlapping atrophy
      patterns of aging and early Alzheimer disease (AD) pathology in gray matter (GM)
      of the brain in vivo. OBJECTIVE: To evaluate the independent and overlapping
      patterns of GM atrophy in normal aging and AD. METHODS: A total of 169
      cognitively normal subjects and 33 persons with probable AD enrolled in the
      longitudinal Cardiovascular Health Study-Cognition Study underwent 3-dimensional
      volumetric MRI scans. Controls remained cognitively normal for at least 5 years
      after their MRI scans and the probable AD subjects were relatively early in their
      clinical course with an average modified Mini-Mental State Examination score of
      76/100. The scans were analyzed using voxel-based morphometry adjusting for total
      intracranial volume, gender, education, and race. RESULTS: With older age, GM
      volume was lower in the sensorimotor and heteromodal association areas in
      frontal, temporal, occipital, and parietal lobes, as well as in the cerebellum
      (false discovery rate p = 0.05). Additional atrophy was observed in the posterior
      hippocampus, thalamus, and middle cingulate gyrus. By contrast, atrophy was seen
      in subjects with AD in the anterior hippocampal/parahippocampal regions and the
      precuneus. Normal aging and AD overlapped in the hippocampal body and the
      entorhinal cortex. CONCLUSION: Brain atrophy with aging was observed in
      supratentorial and infratentorial areas, as well in primary motor, sensory, and
      heteromodal association regions. Age and Alzheimer disease exert independent gray
      matter atrophy patterns but these effects overlapped substantially in the
      hippocampus and entorhinal cortex.

PMID- 19846829
TI  - Early-onset stroke and cerebrovascular disease in adult survivors of childhood
      cancer.

PMID- 19846831
TI  - Exploring white matter microstructure: new insights from diffusion tensor
      imaging.

PMID- 19846830
TI  - Regional pattern of white matter microstructural changes in normal aging, MCI,
      and AD.
AB  - OBJECTIVE: To cross-sectionally compare the regional white matter fractional
      anisotropy (FA) of cognitively normal (CN) older individuals and patients with
      mild cognitive impairment (MCI) and Alzheimer disease (AD), separately focusing
      on the normal-appearing white matter (NAWM) and white matter hyperintensities
      (WMH), and to test the independent effects of presumed degenerative and vascular
      process on FA differences. METHODS: Forty-seven patients with AD, 73 patients
      with MCI, and 95 CN subjects received diffusion tensor imaging and vascular risk
      evaluation. To properly control normal regional variability of FA, we divided
      cerebral white matter into 4 strata as measured from a series of young healthy
      individuals (H1 = highest; H2 = intermediate high; H3 = intermediate low; H4 =
      lowest anisotropy stratum). RESULTS: For overall cerebral white matter, patients
      with AD had significantly lower FA than CN individuals or patients with MCI in
      the regions with higher baseline anisotropy (H1, H2, and H3), corresponding to
      long corticocortical association fibers, but not in H4, which mostly includes
      heterogeneously oriented fibers. Vascular risk showed significant independent
      effects on FA in all strata except H1, which corresponds to the genu and splenium
      of the corpus callosum. Similar results were found within NAWM. FA in WMH was
      significantly lower than NAWM across all strata but was not associated with
      diagnosis or vascular risk. CONCLUSIONS: Both vascular and Alzheimer disease
      degenerative process contribute to microstructural injury of cerebral white
      matter across the spectrum of cognitive ability and have different region
      specific injury patterns.

PMID- 19846832
TI  - Directed aggressive behavior in frontal lobe epilepsy: a video-EEG and ictal
      spect case study.

PMID- 19846833
TI  - Red meets white: do microbleeds link hemorrhagic and ischemic cerebrovascular
      disease?

PMID- 19846834
TI  - Tyrosine sulfation of leukocyte adhesion molecules and chemokine receptors
      promotes atherosclerosis.

PMID- 19846835
TI  - Dimorphisms in the membrane-spanning domain of EPCR impact systemic coagulation.

PMID- 19846836
TI  - The discovery of cellular immunity in the atherosclerotic plaque.
AB  - It is now generally accepted that atherosclerosis is an inflammatory/immune
      disease triggered by LDL accumulation in the artery wall. When discovering T
      cells and the molecular components of a cellular immune response, we proposed
      that atherosclerosis is an inflammatory process with an autoimmune component.
      This notion was met with general skepticism but has gained support from
      experimental and clinical studies. Here we describe some of the early studies
      that helped developing this concept.

PMID- 19846839
TI  - Physicians' views of the Massachusetts Health Care Reform Law--a poll.

PMID- 19846837
TI  - The molecular mechanisms of HDL and associated vesicular trafficking mechanisms
      to mediate cellular lipid homeostasis.
AB  - HDL functions mainly as a cholesterol scavenger, facilitating transport of
      cholesterol to the liver for conversion to bile acids and secretion into the bile
      for elimination or recycling in the enterohepatic bile acid cycle. Because of its
      major function in cholesterol clearance, HDL is in general considered to be
      atheroprotective. From cell cholesterol can be removed by efflux especially to
      apoA-I and HDL as extracellular acceptors which transport the cholesterol to the
      liver for excretion. This process is called reverse cholesterol transport. In
      this context the ATP binding cassette transporter protein ABCA1 facilitates
      cellular cholesterol and phospholipid release to apoA-I-containing HDL
      precursors. In addition ABCA1 plays a role in vesicular lipid transport
      mechanisms required for HDL particle formation. In general to maintain
      intracellular lipid homeostasis, sterols and associated lipids move between
      cellular compartments by vesicular and nonvesicular pathways. However,
      cholesterol sorting on vesicle formation is poorly understood. This review
      summarizes the current knowledge of the molecular mechanisms of HDL and
      associated vesicular trafficking mechanisms to mediate cellular lipid
      homeostasis.

PMID- 19846840
TI  - Reform and the health care workforce--current capacity, future demand.

PMID- 19846841
TI  - Lost in transmission--FDA drug information that never reaches clinicians.

PMID- 19846842
TI  - Doctors, patients, and the need for health care reform.

PMID- 19846843
TI  - Massachusetts health care reform--near-universal coverage at what cost?

PMID- 19846845
TI  - Images in clinical medicine. Thoracic kidney.

PMID- 19846844
TI  - A novel influenza A (H1N1) vaccine in various age groups.
AB  - BACKGROUND: There is an urgent need for a vaccine that is effective against the
      2009 pandemic influenza A (H1N1) virus. METHODS: A split-virus, inactivated
      candidate vaccine against the 2009 H1N1 virus was manufactured, and we evaluated
      its safety and immunogenicity in a randomized clinical trial. Subjects were
      between 3 and 77 years of age, stratified into four age groups. The immunization
      schedule consisted of two vaccinations, 21 days apart. Subjects were injected
      with placebo or with vaccine, with or without alum adjuvant, at doses of 7.5
      microg, 15 microg, or 30 microg. Serologic analysis was performed at baseline and
      on days 21 and 35. RESULTS: A total of 2200 subjects received one dose, and 2103
      (95.6%) received the second dose, of vaccine or placebo. No severe adverse side
      effects associated with the vaccine were noted. In the nonadjuvanted-vaccine
      groups, injection-site or systemic reactions, most mild in nature, were noted in
      5.5 to 15.9% of subjects. Among the subjects receiving 15 microg of nonadjuvanted
      vaccine, a hemagglutination-inhibition titer of 1:40 or more was achieved by day
      21 in 74.5% of subjects between 3 and 11 years of age, 97.1% of subjects between
      12 and 17 years, 97.1% of subjects between 18 and 60 years, and 79.1% of subjects
      61 years of age or older; by day 35, the titer had been achieved in 98.1%, 100%,
      97.1%, and 93.3% of subjects, respectively. The proportion with a titer of 1:40
      or more was generally highest among the subjects receiving 30 microg of vaccine,
      with or without adjuvant. Vaccine without adjuvant was associated with fewer
      local reactions and greater immune responses than was vaccine with adjuvant.
      CONCLUSIONS: These data suggest that a single dose of 15 microg of hemagglutinin
      antigen without alum adjuvant induces a typically protective immune response in
      the majority of subjects between 12 and 60 years of age. Lesser immune responses
      were seen after a single dose of vaccine in younger and older subjects.
      (ClinicalTrials.gov number, NCT00975572).

PMID- 19846846
TI  - Group Health Cooperative--one coverage-and-delivery model for accountable care.

PMID- 19846847
TI  - When diseases disappear--the case of familial dysautonomia.

PMID- 19846848
TI  - Intensity of continuous renal-replacement therapy in critically ill patients.
AB  - BACKGROUND: The optimal intensity of continuous renal-replacement therapy remains
      unclear. We conducted a multicenter, randomized trial to compare the effect of
      this therapy, delivered at two different levels of intensity, on 90-day mortality
      among critically ill patients with acute kidney injury. METHODS: We randomly
      assigned critically ill adults with acute kidney injury to continuous renal
      replacement therapy in the form of postdilution continuous venovenous
      hemodiafiltration with an effluent flow of either 40 ml per kilogram of body
      weight per hour (higher intensity) or 25 ml per kilogram per hour (lower
      intensity). The primary outcome measure was death within 90 days after
      randomization. RESULTS: Of the 1508 enrolled patients, 747 were randomly assigned
      to higher-intensity therapy, and 761 to lower-intensity therapy with continuous
      venovenous hemodiafiltration. Data on primary outcomes were available for 1464
      patients (97.1%): 721 in the higher-intensity group and 743 in the lower
      intensity group. The two study groups had similar baseline characteristics and
      received the study treatment for an average of 6.3 and 5.9 days, respectively
      (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher
      intensity group and 332 deaths in the lower-intensity group, for a mortality of
      44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to
      1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of
      399), as compared with 4.4% of survivors in the lower-intensity group (18 of
      411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI,
      0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity
      group than in the lower-intensity group (65% vs. 54%, P<0.001). CONCLUSIONS: In
      critically ill patients with acute kidney injury, treatment with higher-intensity
      continuous renal-replacement therapy did not reduce mortality at 90 days.
      (ClinicalTrials.gov number, NCT00221013.)

PMID- 19846849
TI  - Strict blood-pressure control and progression of renal failure in children.
AB  - BACKGROUND: Although inhibition of the renin-angiotensin system delays the
      progression of renal failure in adults with chronic kidney disease, the blood
      pressure target for optimal renal protection is controversial. We assessed the
      long-term renoprotective effect of intensified blood-pressure control among
      children who were receiving a fixed high dose of an angiotensin-converting-enzyme
      (ACE) inhibitor. METHODS: After a 6-month run-in period, 385 children, 3 to 18
      years of age, with chronic kidney disease (glomerular filtration rate of 15 to 80
      ml per minute per 1.73 m(2) of body-surface area) received ramipril at a dose of
      6 mg per square meter of body-surface area per day. Patients were randomly
      assigned to intensified blood-pressure control (with a target 24-hour mean
      arterial pressure below the 50th percentile) or conventional blood-pressure
      control (mean arterial pressure in the 50th to 95th percentile), achieved by the
      addition of antihypertensive therapy that does not target the renin-angiotensin
      system; patients were followed for 5 years. The primary end point was the time to
      a decline of 50% in the glomerular filtration rate or progression to end-stage
      renal disease. Secondary end points included changes in blood pressure,
      glomerular filtration rate, and urinary protein excretion. RESULTS: A total of
      29.9% of the patients in the group that received intensified blood-pressure
      control reached the primary end point, as assessed by means of a Kaplan-Meier
      analysis, as compared with 41.7% in the group that received conventional blood
      pressure control (hazard ratio, 0.65; confidence interval, 0.44 to 0.94; P=0.02).
      The two groups did not differ significantly with respect to the type or incidence
      of adverse events or the cumulative rates of withdrawal from the study (28.0% vs.
      26.5%). Proteinuria gradually rebounded during ongoing ACE inhibition after an
      initial 50% decrease, despite persistently good blood-pressure control.
      Achievement of blood-pressure targets and a decrease in proteinuria were
      significant independent predictors of delayed progression of renal disease.
      CONCLUSIONS: Intensified blood-pressure control, with target 24-hour blood
      pressure levels in the low range of normal, confers a substantial benefit with
      respect to renal function among children with chronic kidney disease.
      Reappearance of proteinuria after initial successful pharmacologic blood-pressure
      control is common among children who are receiving long-term ACE inhibition.
      (ClinicalTrials.gov number, NCT00221845.)

PMID- 19846851
TI  - Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma.
AB  - BACKGROUND: Preoperative cisplatin alone may be as effective as cisplatin plus
      doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer
      sectors of the liver that is associated with an alpha-fetoprotein level of >100
      ng per milliliter). METHODS: Children with standard-risk hepatoblastoma who were
      younger than 16 years of age were eligible for inclusion in the study. After they
      received one cycle of cisplatin (80 mg per square meter of body-surface area per
      24 hours), we randomly assigned patients to receive cisplatin (every 14 days) or
      cisplatin plus doxorubicin administered in three preoperative cycles and two
      postoperative cycles. The primary outcome was the rate of complete resection, and
      the trial was powered to test the noninferiority of cisplatin alone (<10%
      difference in the rate of complete resection). RESULTS: Between June 1998 and
      December 2006, 126 patients were randomly assigned to receive cisplatin and 129
      were randomly assigned to receive cisplatin plus doxorubicin. The rate of
      complete resection was 95% in the cisplatin-alone group and 93% in the cisplatin
      doxorubicin group in the intention-to-treat analysis (difference, 1.4%; 95%
      confidence interval [CI], -4.1 to 7.0); these rates were 99% and 95%,
      respectively, in the per-protocol analysis. Three-year event-free survival and
      overall survival were, respectively, 83% (95% CI, 77 to 90) and 95% (95% CI, 91
      to 99) in the cisplatin group, and 85% (95% CI, 79 to 92) and 93% (95% CI, 88 to
      98) in the cisplatin-doxorubicin group (median follow-up, 46 months). Acute grade
      3 or 4 adverse events were more frequent with combination therapy (74.4% vs.
      20.6%). CONCLUSIONS: As compared with cisplatin plus doxorubicin, cisplatin
      monotherapy achieved similar rates of complete resection and survival among
      children with standard-risk hepatoblastoma. Doxorubicin can be safely omitted
      from the treatment of standard-risk hepatoblastoma. (ClinicalTrials.gov number,
      NCT00003912.)

PMID- 19846850
TI  - Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.
AB  - BACKGROUND: Recent studies indicate an increased frequency of mutations in the
      gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's
      disease, among patients with Parkinson's disease. We aimed to ascertain the
      frequency of GBA mutations in an ethnically diverse group of patients with
      Parkinson's disease. METHODS: Sixteen centers participated in our international,
      collaborative study: five from the Americas, six from Europe, two from Israel,
      and three from Asia. Each center genotyped a standard DNA panel to permit
      comparison of the genotyping results across centers. Genotypes and phenotypic
      data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews)
      and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic
      regression models and the Mantel-Haenszel procedure used to estimate odds ratios
      across centers. RESULTS: All 16 centers could detect two GBA mutations, L444P and
      N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of
      patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either
      mutation was found in 3% of patients and less than 1% of controls. GBA was fully
      sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified
      in 7%, showing that limited mutation screening can miss half the mutant alleles.
      The odds ratio for any GBA mutation in patients versus controls was 5.43 across
      centers. As compared with patients who did not carry a GBA mutation, those with a
      GBA mutation presented earlier with the disease, were more likely to have
      affected relatives, and were more likely to have atypical clinical
      manifestations. CONCLUSIONS: Data collected from 16 centers demonstrate that
      there is a strong association between GBA mutations and Parkinson's disease.

PMID- 19846852
TI  - X-linked thrombophilia with a mutant factor IX (factor IX Padua).
AB  - We report a case of juvenile thrombophilia associated with a substitution of
      leucine for arginine at position 338 (R338L) in the factor IX gene (factor IX
      R338L). The level of the mutant factor IX protein in plasma was normal, but the
      clotting activity of factor IX from the proband was approximately eight times the
      normal level. In vitro, recombinant factor IX-R338L had a specific activity that
      was 5 to 10 times as high as that in the recombinant wild-type factor IX. The
      R338 substitution causes a gain-of-function mutation, resulting in factor IX that
      is hyperfunctional.

PMID- 19846853
TI  - Atypical hemolytic-uremic syndrome.

PMID- 19846854
TI  - Images in clinical medicine. Bronchial obstruction after pneumonectomy.

PMID- 19846855
TI  - Case records of the Massachusetts General Hospital. Case 33-2009. A 35-year-old
      woman with fever, abdominal pain, and hypotension after cesarean section.

PMID- 19846856
TI  - Renal support in acute kidney injury--how much is enough?

PMID- 19846857
TI  - Blood-pressure control and delay in progression of kidney disease in children.

PMID- 19846858
TI  - The index lesion and the origin of prostate cancer.

PMID- 19846859
TI  - Inhibition of poly(ADP-ribose) polymerase in BRCA mutation carriers.

PMID- 19846860
TI  - In-hospital cardiopulmonary resuscitation.

PMID- 19846861
TI  - Pay for performance and quality of care in England.

PMID- 19846862
TI  - FOXP3 forkhead domain mutation and regulatory T cells in the IPEX syndrome.

PMID- 19846863
TI  - Psoriasis.

PMID- 19846864
TI  - Use of ribavirin to treat influenza.

PMID- 19846866
TI  - A homolog of formyl peptide receptor-like 1 (FPRL1) inhibitor from Staphylococcus
      aureus (FPRL1 inhibitory protein) that inhibits FPRL1 and FPR.
AB  - The members of the formyl peptide receptor (FPR) family are involved in the
      sensing of chemoattractant substances, including bacteria-derived N-formylated
      peptides and host-derived peptides and proteins. We have recently described two
      chemoattractant receptor inhibitors from Staphylococcus aureus. Chemotaxis
      inhibitory protein of S. aureus (CHIPS) blocks the formyl peptide receptor (FPR)
      and the receptor for complement C5a (C5aR), while FPR-like 1 (FPRL1) inhibitory
      protein (FLIPr) blocks the FPRL1. Here, we describe another staphylococcal
      chemoattractant-inhibiting protein with 73% overall homology to FLIPr and
      identical first 25 aa, which we termed FLIPr-like. This protein inhibits
      neutrophil calcium mobilization and chemotaxis induced by the FPRL1-ligand MMK-1
      and FPR-ligand fMLP. While its FPRL1-inhibitory activity lies in the comparable
      nanomolar range of FLIPr, its antagonism of the FPR is approximately 100-fold
      more potent than that of FLIPr and comparable to that of CHIPS. The second N
      terminal phenylalanine was required for its inhibition of the FPR, but it was
      dispensable for the FPRL1. Furthermore, the deletion of the first seven amino
      acids reduced its antagonism of the FPRL1, and the exchange of the first six
      amino acids with that of CHIPS-conferred receptor specificity. Finally, studies
      with cells transfected with several chemoattractant receptors confirmed that
      FLIPr-like specifically binds to the FPR and FPRL1. In conclusion, the newly
      described excreted protein from S. aureus, FLIPr-like, is a potent inhibitor of
      the FPR- and FPRL1-mediated neutrophil responses and may be used to selectively
      modulate these chemoattractant receptors.

PMID- 19846865
TI  - Targeting a mimotope vaccine to activating Fcgamma receptors empowers dendritic
      cells to prime specific CD8+ T cell responses in tumor-bearing mice.
AB  - A major challenge for inducing antitumor immune responses with native or modified
      tumor/self-Ags in tumor-bearing hosts relates to achieving efficient uptake and
      processing by dendritic cells (DCs) to activate immune effector cells and limit
      the generation of regulatory T cell activity. We analyzed the ability of
      therapeutic DC vaccines expressing a CD166 cross-reactive mimotope of the GD2
      ganglioside, 47-LDA, to selectively expand adoptively transferred, tumor-specific
      T cells in NXS2 neuroblastoma tumor-bearing syngeneic mice. Before the adoptive
      cell transfer and DC vaccination, the tumor-bearing mice were lymphodepleted by
      nonmyeloablative total body irradiation or a myeloablative regimen that required
      bone marrow transplantation. The 47-LDA mimotope was presented to DCs either as a
      linear polypeptide in conjunction with universal Th epitopes or as a fusion
      protein with the murine IgG2a Fc fragment (47-LDA-Fcgamma2a) to deliver the
      antigenic cassette to the activating Fcgamma receptors. We demonstrate that
      immunization of adoptively transferred T cells in tumor-bearing mice with the 47
      LDA mimotope expressed in the context of the activating Fc fusion protein induced
      higher levels of antitumor immune responses and protection than the 47-LDA
      polypeptide-DC vaccine. The antitumor efficacy of the therapeutic 47-LDA
      Fcgamma2a-DC vaccine was comparable to that achieved by a virotherapy-associated
      cancer vaccine using a recombinant oncolytic vaccinia virus expressing the 47-LDA
      Fcgamma2a fusion protein. The latter treatment, however, did not require total
      body irradiation or adoptive cell transfer and resulted in induction of antitumor
      immune responses in the setting of established tolerance, paving the way for
      testing novel anticancer treatment strategies.

PMID- 19846867
TI  - Resistance to vaccinia virus is less dependent on TNF under conditions of
      heterologous immunity.
AB  - TNF has been shown to be important for controlling many pathogens. Here, we
      directly demonstrate using wild-type TNF(-/-) and TNFR1(-/-) mice that TNF does
      play a role in protection against vaccinia virus (VV) infection in naive mice.
      Since VV replication is also partially controlled in lymphocytic choriomeningitis
      virus (LCMV)-immune C57BL/6J mice through the process of heterologous immunity,
      we questioned whether TNF was required in mediating this protection. VV-infected
      LCMV-immune mice that were TNF-deficient as a consequence of genetic deletion or
      receptor blockade demonstrated normal recruitment and selective expansion of
      cross-reactive LCMV-specific memory CD8 T cells and controlled VV infection
      similar to LCMV-immune mice having TNF function. This indicates that neither TNF
      nor lymphotoxin, which uses the same receptor, was required in mediating
      protective heterologous immunity against VV. Indeed, prior immunity to LCMV made
      the role of TNF in protection against VV infection much less important, even
      under conditions of lethal dose inoculum. Thus, heterologous immunity may help
      explain why treatment of patients with anti-TNF compounds is reasonably well
      tolerated with relatively few infectious complications.

PMID- 19846868
TI  - Activated CD4+ T cells dramatically enhance chemotherapeutic tumor responses in
      vitro and in vivo.
AB  - Chemoimmunotherapy has been widely studied in melanoma, with various degrees of
      success. One of the most common approaches is the so-called biochemotherapy,
      which is associated with increased toxicities, but without overall survival
      benefit. Another conventional strategy is the use of chemotherapy as an
      immunomodulator to enhance the effect of cancer vaccines or adoptive cell
      transfer therapy. Based on this approach, recent studies using chemotherapy to
      prepare the host before the infusion of ex vivo-activated, melanoma Ag-specific
      tumor-infiltrating lymphocytes and high dose IL-2 resulted in an impressive
      response rate. However, the development of immunotherapy for the treatment of a
      broad range of cancer type is still lacking. In this study, we report the
      development of a simple yet universal approach termed "chemocentric
      chemoimmunotherapy" that has potential application in the treatment of all cancer
      types. This technique uses nonspecifically activated CD4(+) T cells as a
      chemosensitizer before the administration of chemotherapy. Dramatic enhancement
      of the cytotoxic effect of chemotherapeutic drugs, either active or nonactive as
      single agents, was observed both in in vitro and in vivo human tumor xenograft
      models. Soluble factors secreted from activated CD4(+) T cells, likely acting on
      the tumor and its microenvironment, were responsible for the observed effect.
      Although IFN-gamma played a major role in the therapeutic outcome, it was
      consistently found to be inferior to the use of activated CD4(+) T cells in tumor
      chemosensitization. Our model may provide a plausible mechanism to facilitate
      further understanding, design and development of improved chemoimmunotherapy in
      the treatment of cancer.

PMID- 19846869
TI  - Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces
      histamine content.
AB  - Mast cells are immune effector cells that are involved in allergies and
      inflammation through the release of mediators such as histamine, PGs, and
      cytokines. Uncoupling protein 2 (UCP2) is a mitochondrial protein that inhibits
      insulin secretion from beta cells, possibly through down-regulation of reactive
      oxygen species production. We hypothesized that UCP2 could also regulate mast
      cell activation. In this study, we show that mouse bone marrow mast cells (BMMCs)
      and human leukemic LAD2 mast cells express UCP2. BMMCs from Ucp2(-/-) mice
      exhibited greater histamine release, whereas overexpression of UCP2 in LAD2 cells
      reduced histamine release after both allergic and nonallergic triggers. Ucp2(-/-)
      BMMCs also had elevated histamine content and histidine decarboxylase expression.
      Histamine content was reduced by overexpression of UCP2 or treatment with the
      mitochondrial-targeted superoxide dismutase-mimetic (TBAP) tetrakis(4-benzoic
      acid) porphyrin manganese(III). Furthermore, Ucp2(-/-) BMMCs also had greater
      production of both IL-6 and PGD(2) as well as ERK phosphorylation, which is known
      to regulate PG synthesis. Intradermal administration of substance P, an activator
      of skin mast cells, and challenge with DNP-human serum albumin after passive
      sensitization induced significantly greater vascular permeability in the skin of
      Ucp2(-/-) mice in vivo. Our results suggest that UCP2 can regulate mast cell
      activation.

PMID- 19846870
TI  - Expansion of functionally skewed CD56-negative NK cells in chronic hepatitis C
      virus infection: correlation with outcome of pegylated IFN-alpha and ribavirin
      treatment.
AB  - NK cells are important innate immune effector cells, normally characterized as
      CD56(+)CD3(-) lymphocytes. In this study, we report that CD56(-)CD16(+) NK cells
      expand in many patients with chronic hepatitis C virus infection. These CD56(-)
      NK cells were functionally impaired with respect to cytokine production upon
      target cell recognition, in comparison to CD56(dim) and CD56(bright) NK cell
      subsets. In particular, CD56(-) NK cells were strikingly defective in their
      polyfunctional response as measured by the coexpression of MIP-1beta, IFN-gamma,
      TNF-alpha, and CD107a degranulation. The ability of these cells to mediate three
      or four of these functions was poor; expression of MIP-1beta alone dominated
      their response. CD56(-) NK cells retained expression of receptors such as the
      natural cytotoxicity receptors and NKG2D, whereas the expression of CD57 and
      perforin was lower when compared with CD56(dim) NK cells. Interestingly,
      pretreatment levels of CD56(-) NK cells correlated with the outcome of pegylated
      IFN-alpha and ribavirin treatment. In patients with CD56(-) NK cells in the range
      of healthy subjects, 80% reached a sustained virological response to treatment,
      whereas only 25% of patients with levels clearly above those in healthy subjects
      experienced a sustained virological response. Thus, chronic hepatitis C virus
      infection is associated with an expansion of CD56(-) NK cells functionally skewed
      toward MIP-1beta production only. Furthermore, high levels of these cells reveal
      a disturbance in innate cellular immunity that is associated with an impaired
      ability to respond to antiviral treatment with IFN-alpha and ribavirin.

PMID- 19846871
TI  - The natural cytotoxicity receptor NKp46 is dispensable for IL-22-mediated innate
      intestinal immune defense against Citrobacter rodentium.
AB  - Natural cytotoxicity receptors (including NKp30, NKp44, and NKp46 in humans and
      NKp46 in mice) are type I transmembrane proteins that signal NK cell activation
      via ITAM-containing adapter proteins in response to stress- and pathogen-induced
      ligands. Although murine NKp46 expression (encoded by Ncr1) was thought to be
      predominantly restricted to NK cells, the identification of distinct intestinal
      NKp46(+) cell subsets that express the transcription factor Rorc and produce IL
      22 suggests a broader function for NKp46 that could involve intestinal
      homeostasis and immune defense. Using mice carrying a GFP-modified Ncr1 allele,
      we found normal numbers of gut CD3(-)GFP(+) cells with a similar cell surface
      phenotype and subset distribution in the absence of Ncr1. Splenic and intestinal
      CD3(-)NKp46(+) cell subsets showed distinct patterns of cytokine secretion (IFN
      gamma, IL-22) following activation via NK1.1, NKp46, IL-12 plus IL-18, or IL-23.
      However, IL-22 production was sharply restricted to intestinal CD3(-)GFP(+) cells
      with the CD127(+)NK1.1(-) phenotype and could be induced in an Ncr1-independent
      fashion. Because NKp46 ligands can trigger immune activation in the context of
      infectious pathogens, we assessed the response of wild-type and Ncr-1-deficient
      Rag2(-/-) mice to the enteric pathogen Citrobacter rodentium. No differences in
      the survival or clinical score were observed in C. rodentium-infected Rag2(-/-)
      mice lacking Ncr1, indicating that NKp46 plays a redundant role in the
      differentiation of intestinal IL-22(+) cells that mediate innate defense against
      this pathogen. Our results provide further evidence for functional heterogeneity
      in intestinal NKp46(+) cells that contrast with splenic NK cells.

PMID- 19846872
TI  - Apurinic/apyrimidinic endonuclease 1 is a key modulator of keratinocyte
      inflammatory responses.
AB  - Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1) functions in both DNA
      repair and redox signaling, making it an attractive emerging therapeutic target.
      However, the role of APE1 in cutaneous inflammatory responses is largely unknown.
      In this study, we report that APE1 is a key upstream regulator in TLR2-dependent
      keratinocyte inflammatory responses. We found that nuclear expression of APE1 in
      epidermal layers was markedly up-regulated in psoriatic skin. APE1 was essential
      for the transcriptional activation and nuclear translocation of hypoxia-inducible
      factor-1alpha and NF-kappaB, both of which are crucial for inflammatory signaling
      in keratinocytes. Moreover, APE1 played a crucial role in the expression of TLR2
      mediated inflammatory mediators, including TNF-alpha, CXCL8, and LL-37, in HaCaT
      cells and human primary keratinocytes. Silencing of APE1 attenuated cyclin
      D1/cyclin-dependent kinase 4 expression and phosphorylation of ERK1/2 and Akt,
      thereby affecting keratinocyte proliferation. Importantly, TLR2-induced
      generation of reactive oxygen species contributed to the nuclear translocation
      and expression of APE1, suggesting an autoregulatory circuit in which the
      subcellular localization of APE1 is associated with the production of APE1 per se
      through reactive oxygen species-dependent signaling. Taken together, these
      findings establish a role for APE1 as a master regulator of TLR2-dependent
      inflammatory responses in human keratinocytes.

PMID- 19846874
TI  - Nonhemopoietic cell TLR4 signaling is critical in causing early
      lipopolysaccharide-induced ileus.
AB  - Endotoxin-mediated ileus is poorly understood. Our objective was to
      mechanistically investigate the role of cell-specific TLR4 expression/signaling
      in causing gastrointestinal dysmotility. TLR4 chimeras and CSF-1-dependent
      macrophage-deficient mice were subjected to i.p. ultrapure (UP)-LPS (5 mg/kg). At
      6 h, gastric emptying and gastrointestinal transit assessed in vivo motility, and
      jejunal circular muscle contractility was measured in vitro. Muscularis
      infiltration of neutrophils and monocytes were counted, and intestinal muscularis
      inflammatory mediators were quantified by quantitative PCR. Demonstrating TLR4
      dependency, UP-LPS-induced gastric stasis and ileus of TLR4(WT) mice were absent
      in mutant TLR4(LPS-d) mice. Unexpectedly, engraftment of TLR4-mutant bone marrow
      into TLR4-competent mice (bmTLR4(LPS-d)/TLR4(WT)) exhibited a significant transit
      delay to UP-LPS similar to bmTLR4(WT)/TLR4(WT) mice. CSF-1(-/-) mice were not
      protected from ileus. Contrary, UP-LPS-treated bmTLR4(WT)/TLR4(LPS-d) and
      bmTLR4(LPS-d)/TLR4(LPS-d) mice had normal transit. No leukocytic infiltration was
      detected at 6 h. Spontaneous jejunal contractions were markedly suppressed in UP
      LPS-treated TLR4-competent mice, but bethanechol-stimulated contractions were not
      altered by UP-LPS in any group. UP-LPS-induced inflammatory mRNAs in a TLR4
      dependent manner, but TLR4 mRNA itself was not significantly altered. In chimera
      mice, UP-LPS induction of IL-1beta and IL-10 were hemopoietic dependent, and GM
      CSF was nonhemopoietic dependent, whereas IL-6 and inducible NO synthase were
      derived from both cell types. Hemopoietic and nonhemopoietic cells contribute to
      TLR4-sensitive muscularis inflammatory signaling, but nonhemopoietic TLR4
      signaling plays an exclusive primary role in causing functional UP-LPS-induced
      gastric stasis and ileus. Direct LPS suppression of spontaneous contractility
      participates in mediating early TLR4-transduced dysmotility.

PMID- 19846873
TI  - Both TRIF- and MyD88-dependent signaling contribute to host defense against
      pulmonary Klebsiella infection.
AB  - Klebsiella pneumoniae causes extensive lung damage. TLR signaling involves
      adaptors TRIF and MyD88. However, the relative contribution of TRIF and MyD88
      signaling in host defense against pulmonary K. pneumoniae infection has not been
      elucidated. Therefore, we investigated the role of TRIF and MyD88 in K.
      pneumoniae pneumonia. TRIF(-/-) mice infected with K. pneumoniae showed impaired
      survival and reduced bacterial clearance, neutrophil influx, histopathologic
      evidence of inflammation, and TNF-alpha, IL-6, KC, MIP-2, but not LIX, expression
      in the lungs. In addition, K. pneumoniae-induced late NF-kappaB activation and
      phosphorylation of MAPKs was attenuated in the lungs of TRIF(-/-) mice. However,
      MyD88(-/-) mice infected with K. pneumoniae showed a much more remarkable
      phenotype, including impaired survival and reduced bacterial clearance,
      histopathology, and TNF-alpha, IL-6, KC, MIP-2, and LIX expression with almost no
      neutrophil influx in the lungs. In MyD88(-/-) mice, K. pneumoniae-induced early
      NF-kappaB and MAPK activation in the lungs was also reduced. Furthermore, the
      role of MyD88 is dominant over TRIF because TRIF/MyD88 double knockout mice
      displayed a more pronounced phenotype than TRIF(-/-) mice. Moreover, human
      alveolar macrophages pretreated with MyD88 blocking peptide showed attenuated TNF
      alpha, IL-6, and IL-8 expression. Also, C57BL/6 mice pretreated with MyD88
      blocking peptide exhibited attenuation in K. pneumoniae-induced neutrophil influx
      and enhanced bacterial burden in the lungs and dissemination. Overall, this
      investigation provides new insights into the TRIF and MyD88 signaling triggered
      by pulmonary K. pneumoniae infection in the lungs and demonstrate the therapeutic
      potential of MyD88 in reducing excessive neutrophil influx in human disease
      during Gram-negative bacterial pneumonia.

PMID- 19846875
TI  - Activation of the cholinergic anti-inflammatory system by nicotine attenuates
      neuroinflammation via suppression of Th1 and Th17 responses.
AB  - The alpha7 nicotinic acetylcholine receptor (nAChR) was recently described as an
      anti-inflammatory target in both macrophages and T cells. Its expression by
      immune cells may explain the epidemiological data claiming a negative link
      between cigarette smoking and several inflammatory diseases. In this study, we
      determined the immunological effects of alpha7 nAChR activation by nicotine. Our
      results indicate that the alpha7 nAChR is expressed on the surface of CD4(+) T
      cells and that this expression is up-regulated upon immune activation. Nicotine
      reduced T cell proliferation in response to an encephalitogenic Ag, as well as
      the production of Th1 (TNF-alpha and IFN-gamma) and Th17 cytokines (IL-17, IL
      17F, IL-21, and IL-22). IL-4 production was increased in the same setting.
      Attenuation of the Th1 and Th17 lineages was accompanied by reduced T-bet (50%)
      and increased GATA-3 (350%) expression. Overall, nicotine induced a shift to the
      Th2 lineage. However, alpha7(-/-)-derived T cells were unaffected by nicotine.
      Furthermore, nicotine reduced NF-kappaB-mediated transcription as measured by IL
      2 and IkappaB transcription. In vivo, administration of nicotine (2 mg/kg s.c.)
      suppressed the severity of CD4(+) T cell-mediated disease experimental autoimmune
      encephalomyelitis. alpha7(-/-) mice were refractory to nicotine treatment,
      although disease severity in those animals was reduced, due to impairment in Ag
      presentation. Accordingly, CD4(+) and CD11b(+) cells infiltration into the CNS,
      demyelination, and axonal loss were reduced. Our data implicate a role for the
      alpha7 nAChR in immune modulation and suggest that alpha7 nAChR agonists may be
      effective in the treatment of inflammatory disorders.

PMID- 19846876
TI  - Adoptive transfer of T lymphocytes sensitized against the prion protein
      attenuates prion invasion in scrapie-infected mice.
AB  - There is to date no effective way of preventing or curing neurodegenerative
      diseases such as Alzheimer disease or transmissible spongiform encephalopathies.
      The idea of treating those conditions by immunological approaches has
      progressively emerged over the last ten years. Encouraging results have been
      reported in Alzheimer disease and in peripheral forms of mouse prion diseases
      following passive injection of Abs or active immunization against the peptides or
      proteins presumably at the origin of those disorders. Still, major difficulties
      persist due to some characteristics of those conditions such as slow evolution,
      brain location, uncertainties regarding precise pathogenic pathways, and, above
      all, the fact that the target Ag is self, meaning that it is poorly immunogenic
      and potentially harmful if tolerance was transgressed. To analyze some of those
      difficulties, we are developing adoptive cell transfer approaches. In this study,
      lymphocytes sensitized against the prion protein in nontolerant Prnp(-/-) mice
      were transferred into histocompatible wild-type recipients which were partly or
      totally devoid of their own lymphocytes. Under such conditions, we found that the
      engrafted T lymphocytes resisted peripheral tolerance, remained reactive for
      several months against epitopes of the prion protein, and significantly
      attenuated the progression of prions in secondary lymphoid organs with subsequent
      delay in the evolution of the neurological disease. Interestingly, those
      protective T lymphocytes secreted lymphokines and migrated more readily into the
      host CNS but did not appear to be engaged in cooperation with host B cells for Ab
      production.

PMID- 19846877
TI  - Immunomodulatory activity of oenothein B isolated from Epilobium angustifolium.
AB  - Epilobium angustifolium has been traditionally used to treat of a number of
      diseases; however, not much is known regarding its effect on innate immune cells.
      In this study, we report that extracts of E. angustifolium activated functional
      responses in neutrophils and monocyte/macrophages. Activity-guided fractionation,
      followed by mass spectroscopy and NMR analysis, resulted in the identification of
      oenothein B as the primary component responsible for phagocyte activation.
      Oenothein B, a dimeric hydrolysable tannin, dose-dependently induced a number of
      phagocyte functions in vitro, including intracellular Ca(2+) flux, production of
      reactive oxygen species, chemotaxis, NF-kappaB activation, and proinflammatory
      cytokine production. Furthermore, oenothein B was active in vivo, inducing
      keratinocyte chemoattractant production and neutrophil recruitment to the
      peritoneum after intraperitoneal administration. Biological activity required the
      full oenothein B structure, as substructures of oenothein B (pyrocatechol, gallic
      acid, pyrogallol, 3,4-dihydroxybenzoic acid) were all inactive. The ability of
      oenothein B to modulate phagocyte functions in vitro and in vivo suggests that
      this compound is responsible for at least part of the therapeutic properties of
      E. angustifolium extracts.

PMID- 19846878
TI  - Adenosine blocks IFN-gamma-induced phosphorylation of STAT1 on serine 727 to
      reduce macrophage activation.
AB  - Macrophages are activated by IFN-gamma, a proinflammatory and proatherogenic
      cytokine that mediates its downstream effects primarily through STAT1. IFN-gamma
      signaling induces phosphorylation of two STAT1 residues: Tyr(701) (Y701), which
      facilitates dimerization, nuclear translocation, and DNA binding; and Ser(727)
      (S727), which enables maximal STAT1 transcription activity. Immunosuppressive
      molecules such as adenosine in the cellular microenvironment can reduce
      macrophage inflammatory and atherogenic functions through receptor-mediated
      signaling pathways. We hypothesized that adenosine achieves these protective
      effects by interrupting IFN-gamma signaling in activated macrophages. This
      investigation demonstrates that adding adenosine to IFN-gamma-stimulated murine
      RAW 264.7 and human THP-1 macrophages results in unique modulation of STAT1
      serine and tyrosine phosphorylation events. We show that adenosine inhibits IFN
      gamma-induced STAT1 S727 phosphorylation by >30% and phosphoserine-mediated
      transcriptional activity by 58% but has no effect on phosphorylation of Y701 or
      receptor-associated JAK tyrosine kinases. Inhibition of the adenosine A(3)
      receptor with a subtype-specific antagonist (MRS 1191 in RAW 264.7 cells and MRS
      1220 in THP-1 cells) reverses this adenosine suppressive effect on STAT1
      phosphoserine status by 25-50%. Further, RAW 264.7 A(3) receptor stimulation with
      Cl-IB-MECA reduces IFN-gamma-induced STAT1 transcriptional activity by 45% and
      STAT1-dependent gene expression by up to 80%. These data suggest that A(3)
      receptor signaling is key to adenosine-mediated STAT1 modulation and anti
      inflammatory action in IFN-gamma-activated mouse and human macrophages. Because
      STAT1 plays a key role in IFN-gamma-induced inflammation and foam cell
      transformation, a better understanding of the mechanisms underlying STAT1
      deactivation by adenosine may improve preventative and therapeutic approaches to
      vascular disease.

PMID- 19846879
TI  - Nodavirus infection of sea bass (Dicentrarchus labrax) induces up-regulation of
      galectin-1 expression with potential anti-inflammatory activity.
AB  - Sea bass nervous necrosis virus is the causative agent of viral nervous necrosis,
      a disease responsible of high economic losses in larval and juvenile stages of
      cultured sea bass (Dicentrarchus labrax). To identify genes potentially involved
      in antiviral immune defense, gene expression profiles in response to nodavirus
      infection were investigated in sea bass head kidney using the suppression
      subtractive hybridization (SSH) technique. A total of 8.7% of the expressed
      sequence tags found in the SSH library showed significant similarities with
      immune genes, of which a prototype galectin (Sbgalectin-1), two C-type lectins
      (SbCLA and SbCLB) from groups II and VII, respectively, and a short pentraxin
      (Sbpentraxin) were selected for further characterization. Results of SSH were
      validated by in vivo up-regulation of expression of Sbgalectin-1, SbCLA, and
      SbCLB in response to nodavirus infection. To examine the potential role(s) of
      Sbgalectin-1 in response to nodavirus infection in further detail, the
      recombinant protein (rSbgalectin-1) was produced, and selected functional assays
      were conducted. A dose-dependent decrease of respiratory burst was observed in
      sea bass head kidney leukocytes after incubation with increasing concentrations
      of rSbgalectin-1. A decrease in IL-1beta, TNF-alpha, and Mx expression was
      observed in the brain of sea bass simultaneously injected with nodavirus and
      rSbgalectin-1 compared with those infected with nodavirus alone. Moreover, the
      protein was detected in the brain from infected fish, which is the main target of
      the virus. These results suggest a potential anti-inflammatory, protective role
      of Sbgalectin-1 during viral infection.

PMID- 19846880
TI  - Enterobacter sakazakii targets DC-SIGN to induce immunosuppressive responses in
      dendritic cells by modulating MAPKs.
AB  - Enterobacter sakazakii (ES) is an emerging pathogen that causes meningitis and
      necrotizing enterocolitis in infants. Dendritic cells (DCs) are professional
      phagocytic cells that play an essential role in host defense against invading
      pathogens; however, the interaction of ES with DCs is not known. In this study,
      we demonstrate that ES targets DC-specific ICAM nonintegrin (DC-SIGN) to survive
      in myeloid DCs for which outer membrane protein A (OmpA) expression in ES is
      critical, although it is not required for uptake. In addition, DC-SIGN expression
      was sufficient to cause a significant invasion by ES in HeLa cells and intestinal
      epithelial cells, which are normally not invaded by ES. OmpA(+) ES prevented the
      maturation of DCs by triggering the production of high levels of IL-10 and TGF
      beta and by suppressing the activation of MAPKs. Pretreatment of DCs with Abs to
      IL-10 and TGF-beta or of bacteria with anti-OmpA Abs significantly enhanced the
      maturation markers on DCs. Furthermore, DCs pretreated with various inhibitors of
      MAPKs prohibited the increased production of proinflammatory cytokines stimulated
      by LPS or OmpA(-) ES. LPS pretreatment followed by OmpA(+) ES infection of DCs
      failed to induce maturation of DCs, indicating that OmpA(+) ES renders the cells
      in immunosuppressive state to external stimuli. Similarly, OmpA(+) ES-infected
      DCs failed to present Ag to T cells as indicated by the inability of T cells to
      proliferate in MLR. We conclude that ES interacts with DC-SIGN to subvert the
      host immune responses by disarming MAPK pathway in DCs.

PMID- 19846881
TI  - Epigenetic regulation of TLR4 gene expression in intestinal epithelial cells for
      the maintenance of intestinal homeostasis.
AB  - Intestinal epithelial cells (IECs) are continuously exposed to large numbers of
      commensal bacteria but are relatively insensitive to them, thereby averting an
      excessive inflammatory reaction. In this study, we show that the low
      responsiveness of human IEC lines to LPS was mainly brought about by a down
      regulation of TLR4 gene transcription. Additionally, the presence of an IEC
      specific repressor element in the 5' region of the TLR4 gene and binding of a NF
      to the element was shown. The transcription factor ZNF160, which was expressed
      more abundantly in a LPS-low responder IEC line than in a LPS-high responder IEC
      line, repressed TLR4 gene transcription. ZNF160 is known to interact with the
      scaffold protein KAP1 via its N terminus to recruit histone deacetylase. Histone
      deacetylation, as well as DNA methylation, at the 5' region of the TLR4 gene was
      significantly higher in LPS-low responder IEC lines than in a monocyte line or a
      LPS-high responder IEC line. It was demonstrated that TLR4 gene transcription was
      repressed by these epigenetic regulations, which were, at least in part,
      dependent on ZNF160. Down-regulaton of TLR4 gene expression by these mechanisms
      in IECs possibly contributes to the maintainance of homeostasis in the intestinal
      commensal system.

PMID- 19846882
TI  - Induction of cross-priming of naive CD8+ T lymphocytes by recombinant bacillus
      Calmette-Guerin that secretes heat shock protein 70-major membrane protein-II
      fusion protein.
AB  - Because Mycobacterium bovis bacillus Calmette-Guerin (BCG) unconvincingly
      activates human naive CD8(+) T cells, a rBCG (BCG-70M) that secretes a fusion
      protein comprising BCG-derived heat shock protein (HSP)70 and Mycobacterium
      leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of
      M. leprae, was newly constructed to potentiate the ability of activating naive
      CD8(+) T cells through dendritic cells (DC). BCG-70M secreted HSP70-MMP-II fusion
      protein in vitro, which stimulated DC to produce IL-12p70 through TLR2. BCG-70M
      infected DC activated not only memory and naive CD8(+) T cells, but also CD4(+) T
      cells of both types to produce IFN-gamma. The activation of these naive T cells
      by BCG-70M was dependent on the MHC and CD86 molecules on BCG-70M-infected DC,
      and was significantly inhibited by pretreatment of DC with chloroquine. Both
      brefeldin A and lactacystin significantly inhibited the activation of naive
      CD8(+) T cells by BCG-70M through DC. Thus, the CD8(+) T cell activation may be
      induced by cross-presentation of Ags through a TAP- and proteosome-dependent
      cytosolic pathway. When naive CD8(+) T cells were stimulated by BCG-70M-infected
      DC in the presence of naive CD4(+) T cells, CD62L(low)CD8(+) T cells and perforin
      producing CD8(+) T cells were efficiently produced. MMP-II-reactive CD4(+) and
      CD8(+) memory T cells were efficiently produced in C57BL/6 mice by infection with
      BCG-70M. These results indicate that BCG-70M activated DC, CD4(+) T cells, and
      CD8(+) T cells, and the combination of HSP70 and MMP-II may be useful for
      inducing better T cell activation.

PMID- 19846883
TI  - Cysteinyl-leukotriene receptor type 1 expression and function is down-regulated
      during monocyte-derived dendritic cell maturation with zymosan: involvement of IL
      10 and prostaglandins.
AB  - TLRs sense microbial products and initiate adaptive immune responses by
      activating dendritic cells (DCs). DCs have been shown to produce leukotrienes
      and, conversely, leukotrienes are known to modulate several DC functions. In this
      study, we examined the modulation of expression and function of cysteinyl
      leukotriene receptor type 1 (CysLT1) on human monocyte-derived DCs during their
      differentiation and subsequent maturation with zymosan, a TLR2 agonist.
      Maturation of DCs with zymosan reduced CysLT1 mRNA levels and protein expression
      in a time-dependent fashion and was associated with a diminution of functional
      responsiveness to leukotriene D(4) as assessed by intracellular calcium
      mobilization, CCL2 and CCL3 production, and chemotaxis. The effect of zymosan was
      mediated by both TLR2 and dectin-1 activation. Zymosan also induced a rapid
      expression of cyclooxygenase-2 and the production of PGE(2) and IL-10. Addition
      of an anti-IL-10 neutralizing Ab or inhibitors of cyclooxygenase greatly reduced
      the ability of zymosan to down-regulate CysLT1 expression. Down-regulation of
      CysLT1 expression by zymosan could be reproduced by a combination of IL-10 and
      PGE(2), and was dependent on MAPK activation. Taken together, our findings
      indicate that zymosan down-regulates CysLT1 expression in DCs with consequently
      reduced functional responsiveness of the cells to leukotriene D(4) stimulation.
      This effect is partially dependent on an endogenous production of PGs and IL-10
      by DCs.

PMID- 19846884
TI  - Novel role of Pin1 induction in type II collagen-mediated rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic
      inflammation in joints and subsequent destruction of cartilage and bone.
      Inflammatory mediators such as PGs and proinflammatory cytokines contribute to RA
      progress. Pin1, a peptidyl prolyl isomerase, plays important pathophysiological
      roles in several diseases, including cancer and neurodegeneration. We found that
      both Pin1 and cyclooxygenase-2 (COX-2) were highly expressed in ankle tissues of
      type II collagen-induced RA mice. HTB-94 cells overexpressing Pin1 and primary
      cultured human chondrocytes showed increased basal expression of proinflammatory
      proteins (COX-2, inducible NO synthase, TNF-alpha, and IL-1beta). Site-directed
      mutagenesis revealed that Pin1-mediated transcriptional activation of COX-2 was
      coordinately regulated by NF-kappaB, CREB, and C/EBP. Gel shift, reporter gene,
      and Western blot analyses confirmed that NF-kappaB, CREB, and C/EBP were
      consistently activated in chondrocytes overexpressing Pin1. Treatment of RA mice
      with juglone, a chemical inhibitor of Pin1, significantly reduced RA progress and
      COX-2 expression in the ankle tissues. Moreover, juglone dose dependently
      decreased the basal COX-2 expression in primary cultured chondrocytes from RA
      patients. These results demonstrate that Pin1 induction during RA progress
      stimulates proinflammatory protein expression by activating NF-kappaB, CREB, and
      C/EBP, and suggest that Pin1 is a potential therapeutic target of RA.

PMID- 19846885
TI  - Externally triggered egress is the major fate of Toxoplasma gondii during acute
      infection.
AB  - The apicomplexan parasite Toxoplasma gondii expands during acute infection via a
      cycle of invasion, intracellular replication, and lytic egress. Physiological
      regulation has not yet been demonstrated for either invasion or egress. We now
      report that, in contrast to cell culture systems, in which egress occurs only
      after five or more parasite divisions (2-3 days), intracellular residence is
      strikingly abbreviated in inflammatory cells in vivo, and early egress (after
      zero to two divisions) is the dominant parasite fate in acutely infected mice.
      Adoptive transfer experiments demonstrate rapid, reciprocal, kinetically uniform
      parasite transfer between donor and recipient compartments, with a t(1/2) of
      approximately 3 h. Inflammatory macrophages are major participants in this cycle
      of lytic egress and reinfection, which drives rapid macrophage turnover.
      Inflammatory triggering cells, principally macrophages, elicit egress in infected
      target macrophages, a process we term externally triggered egress (ETE). The
      mechanism of ETE does not require reactive oxygen or nitrogen species, the
      mitochondrial permeability transition pore, or a variety of signal transduction
      mediators, but is dependent on intracellular calcium and is highly sensitive to
      SB203580, an inhibitor of p38 MAPK as well as a related parasite-encoded kinase.
      SB203580 both inhibited the initiation of ETE and altered the progression of
      egress. Parasites recently completing a cycle of egress and reinfection were
      preferentially restricted in vivo, supporting a model in which ETE may favor host
      defense by a process of haven disruption. ETE represents a novel example of
      interaction between a parasite infectious cycle and host microenvironment.

PMID- 19846886
TI  - An in vitro model of differentiation of memory B cells into plasmablasts and
      plasma cells including detailed phenotypic and molecular characterization.
AB  - Human plasma cells (PCs) and their precursors play an essential role in humoral
      immune response but are rare and difficult to harvest. We report the generation
      of human syndecan-1(+) and immunoglobulin secreting PCs starting from memory B
      cells in a 3-step and 10-day (D) culture, including a 6-fold cell amplification.
      We report the detailed phenotypic and Affymetrix gene expression profiles of
      these in vitro PCs as well as of intermediate cells (activated B cells and
      plasmablasts) compared with memory B cells and bone marrow PCs, which is
      accessible through an open web ATLAS (http://amazonia.transcriptome.eu/). We show
      this B cell-to-PC differentiation to involve IRF4 and AICDA expressions in D4
      activated B cells, decrease of PAX5 and BCL6 expressions, and increase in PRDM1
      and XBP1 expressions in D7 plasmablasts and D10 PCs. It involves down-regulation
      of genes controlled by Pax5 and induction of genes controlled by Blimp-1 and XBP1
      (unfold protein response). The detailed phenotype of D10 PCs resembles that of
      peripheral blood PCs detected after immunization of healthy donors. This in vitro
      model will facilitate further studies in PC biology. It will likewise be helpful
      to study PC dyscrasias, including multiple myeloma.

PMID- 19846887
TI  - The mouse mutation "thrombocytopenia and cardiomyopathy" (trac) disrupts Abcg5: a
      spontaneous single gene model for human hereditary
      phytosterolemia/sitosterolemia.
AB  - The spontaneous mouse mutation "thrombocytopenia and cardiomyopathy" (trac)
      causes macrothrombocytopenia, prolonged bleeding times, anemia, leukopenia,
      infertility, cardiomyopathy, and shortened life span. Homozygotes show a 20-fold
      decrease in platelet numbers and a 3-fold increase in platelet size with
      structural alterations and functional impairments in activation and aggregation.
      Megakaryocytes in trac/trac mice are present in increased numbers, have poorly
      developed demarcation membrane systems, and have decreased polyploidy. The
      thrombocytopenia is not intrinsic to defects at the level of hematopoietic
      progenitor cells but is associated with a microenvironmental abnormality. The
      trac mutation maps to mouse chromosome 17, syntenic with human chromosome 2p21
      22. A G to A mutation in exon 10 of the adenosine triphosphate (ATP)-binding
      cassette subfamily G, member 5 (Abcg5) gene, alters a tryptophan codon (UGG) to a
      premature stop codon (UAG). Crosses with mice doubly transgenic for the human
      ABCG5 and ABCG8 genes rescued platelet counts and volumes. ABCG5 and ABCG8 form a
      functional complex that limits dietary phytosterol accumulation. Phytosterolemia
      in trac/trac mice confirmed a functional defect in the ABCG5/ABCG8 transport
      system. The trac mutation provides a new clinically significant animal model for
      human phytosterolemia and provides a new means for studying the role of
      phytosterols in hematologic diseases and testing therapeutic interventions.

PMID- 19846888
TI  - Identification of microRNA expression patterns and definition of a microRNA/mRNA
      regulatory network in distinct molecular groups of multiple myeloma.
AB  - To date, little evidence of miRNA expression/deregulation in multiple myeloma has
      been reported. To characterize miRNA in the context of the major multiple myeloma
      molecular types, we generated miRNA expression profiles of highly purified
      malignant plasma cells from 40 primary tumors. Furthermore, transcriptional
      profiles, available for all patients, were used to investigate the occurrence of
      miRNA/predicted target mRNA pair anticorrelations, and the miRNA and genome-wide
      DNA data were integrated in a subset of patients to evaluate the influence of
      allelic imbalances on miRNA expression. Differential miRNA expression patterns
      were identified, which were mainly associated with the major IGH translocations;
      particularly, t(4;14) patients showed specific overexpression of let-7e, miR-125a
      5p, and miR-99b belonging to a cluster at 19q13.33. The occurrence of other
      lesions (ie, 1q gain, 13q and 17p deletions, and hyperdiploidy) was slightly
      characterized by specific miRNA signatures. Furthermore, the occurrence of
      several allelic imbalances or loss of heterozygosity was found significantly
      associated with the altered expression of miRNAs located in the involved regions,
      such as let-7b at 22q13.31 or miR-140-3p at 16q22. Finally, the integrative
      analysis based on computational target prediction and miRNA/mRNA profiling
      defined a network of putative functional miRNA-target regulatory relations
      supported by expression data.

PMID- 19846889
TI  - International consensus report on the investigation and management of primary
      immune thrombocytopenia.
AB  - Previously published guidelines for the diagnosis and management of primary
      immune thrombocytopenia (ITP) require updating largely due to the introduction of
      new classes of therapeutic agents, and a greater understanding of the disease
      pathophysiology. However, treatment-related decisions still remain principally
      dependent on clinical expertise or patient preference rather than high-quality
      clinical trial evidence. This consensus document aims to report on new data and
      provide consensus-based recommendations relating to diagnosis and treatment of
      ITP in adults, in children, and during pregnancy. The inclusion of summary tables
      within this document, supported by information tables in the online appendices,
      is intended to aid in clinical decision making.

PMID- 19846890
TI  - Astaxanthin reduces oxidative stress, but not aortic damage in atherosclerotic
      rabbits.
AB  - We evaluated whether carotenoid astaxanthin (ASX) could prevent oxidative and
      atherosclerotic damage in rabbits. Rabbits received regular chow (control) or an
      atherogenic diet (1% cholesterol) alone or supplemented with 50, 100, and 500 mg%
      ASX for 60 days (n = 5-9 per group). The atherogenic diet increased the serum
      cholesterol levels and the ratio of the intima/media area in the aortic arch.
      These changes were not prevented by ASX. Atherosclerotic rabbits showed increased
      aortic lipid peroxidation and nonprotein thiol group (NPSH) levels along with
      inhibition of glutathione peroxidase (GSH-Px). All ASX doses attenuated lipid
      peroxidation and the increase in NPSH but not the inhibition of GSH-Px. Aortic
      superoxide dismutase (SOD), catalase (CAT), and thioredoxin reductase (TrxR)
      activities were enhanced in atherosclerotic rabbits. Although all ASX doses
      prevented the increase in SOD activity, only 100 and 500 mg% ASX prevented the
      increase in CAT activity. Furthermore, these same doses partially prevented the
      increase in TrxR activity, while 50 mg% ASX completely prevented the effects of
      the atherogenic diet on this enzyme. However, ASX did not attenuate the
      hypercholesterolemia or the atherosclerotic lesions caused by the atherogenic
      diet at any of the doses evaluated. Our results indicate that although ASX did
      not prevent hypercholesterolemia or atherosclerotic lesions, it could play a
      beneficial role by preventing lipid peroxidation and changes in antioxidant
      enzyme activities.

PMID- 19846891
TI  - Contribution of different triggers to the gastric accommodation reflex in humans.
AB  - Accommodation of the stomach consists of a vagally mediated relaxation of the
      proximal stomach, providing the meal with a reservoir. Our aim was to study
      whether, similar to other vagally mediated processes, the accommodation reflex is
      also determined by cephalic, oropharyngeal, gastric, and intestinal phases.
      Eleven healthy subjects underwent in randomized order five gastric barostat
      studies and two satiety drinking tests. In all studies, isobaric tone
      measurements (at minimal distending pressure + 2 mmHg) were performed 20 min
      before and 20 min after a nutrient stimulus. The stimuli included only visual and
      olfactory exposure to a meal (cephalic stimulation), taking liquid nutrient in
      the mouth without swallowing (sham feeding), ingestion of a 200-ml 300-kcal
      nutrient meal with blocked outflow to the pylorus (gastric retention), and meal
      infusion through a nasointestinal tube (duodenal instillation), or normal
      ingestion (control). During satiety testing, subjects ingested liquid nutrient at
      a fixed rate of 15 ml/min until maximum satiety, with an inflated or deflated
      intrapyloric balloon assembly. Progressively bigger gastric relaxatory responses
      were seen with cephalic stimulation (18 +/- 19 ml), sham feeding (54 +/- 21 ml),
      gastric retention (95 +/- 47), duodenal instillation (144 +/- 33), and control
      (232 +/- 33 ml). The amount of nutrient ingested at maximum satiety was
      significantly lower with an inflated intrapyloric balloon (1,223 +/- 103 vs.
      1,392 +/- 124 ml, P < 0.05). The accommodation reflex in humans lacks a cephalic
      phase, but it can be activated from the oropharynx, the stomach, and the
      duodenum. Blocking passage to the duodenum significantly decreases the amplitude
      of the accommodation reflex and induces early satiety.

PMID- 19846893
TI  - The ethics of sham invasive intervention trials.

PMID- 19846894
TI  - Recommendations for safety planning, data collection, evaluation and reporting
      during drug, biologic and vaccine development: a report of the safety planning,
      evaluation, and reporting team.
AB  - BACKGROUND: The Safety Planning, Evaluation and Reporting Team (SPERT) was formed
      in 2006 by the Pharmaceutical Research and Manufacturers of America. PURPOSE:
      SPERT's goal was to propose a pharmaceutical industry standard for safety
      planning, data collection, evaluation, and reporting, beginning with planning
      first-in-human studies and continuing through the planning of the post-product
      approval period. METHODS: SPERT's recommendations are based on our review of
      relevant literature and on consensus reached in our discussions. RESULTS: An
      important recommendation is that sponsors create a Program Safety Analysis Plan
      early in development. We also give recommendations for the planning of repeated,
      cumulative meta-analyses of the safety data obtained from the studies conducted
      within the development program. These include clear definitions of adverse events
      of special interest and standardization of many aspects of data collection and
      study design. We describe a 3-tier system for signal detection and analysis of
      adverse events and highlight proposals for reducing "false positive" safety
      findings. We recommend that sponsors review the aggregated safety data on a
      regular and ongoing basis throughout the development program, rather than waiting
      until the time of submission. LIMITATIONS: We recognize that there may be other
      valid approaches. CONCLUSIONS: The proactive approach we advocate has the
      potential to benefit patients and health care providers by providing more
      comprehensive safety information at the time of new product marketing and beyond.

PMID- 19846892
TI  - A review of the molecular mechanisms of chemically induced neoplasia in rat and
      mouse models in National Toxicology Program bioassays and their relevance to
      human cancer.
AB  - Tumor response in the B6C3F1 mouse, F344 rat, and other animal models following
      exposure to various compounds provides evidence that people exposed to these or
      similar compounds may be at risk for developing cancer. Although tumors in
      rodents and humans are often morphologically similar, underlying mechanisms of
      tumorigenesis are often unknown and may be different between the species.
      Therefore, the relevance of an animal tumor response to human health would be
      better determined if the molecular pathogenesis were understood. The underlying
      molecular mechanisms leading to carcinogenesis are complex and involve multiple
      genetic and epigenetic events and other factors. To address the molecular
      pathogenesis of environmental carcinogens, the authors examine rodent tumors
      (e.g., lung, colon, mammary gland, skin, brain, mesothelioma) for alterations in
      cancer genes and epigenetic events that are associated with human cancer.
      National Toxicology Program (NTP) studies have identified several genetic
      alterations in chemically induced rodent neoplasms that are important in human
      cancer. Identification of such alterations in rodent models of chemical
      carcinogenesis caused by exposure to environmental contaminants, occupational
      chemicals, and other compounds lends further support that they are of potential
      human health risk. These studies also emphasize the importance of molecular
      evaluation of chemically induced rodent tumors for providing greater public
      health significance for NTP evaluated compounds.

PMID- 19846895
TI  - Comment on paper by Crowe et al.

PMID- 19846896
TI  - On the importance of heterogeneity in meta-analysis.

PMID- 19846898
TI  - Prospective randomized single-blinded trial of endoscopic stenting for chronic
      pancreatitis.

PMID- 19846903
TI  - Apoptosis induced by capsaicin and resveratrol in colon carcinoma cells requires
      nitric oxide production and caspase activation.
AB  - Although many studies have focused on anticarcinogenic properties of capsaicin
      and resveratrol, molecular mechanisms by which they selectively induce apoptosis
      are incompletely characterized. We examined the role of nitric oxide (NO) and
      influence of p53 status during apoptosis induced by these agents in two isogenic
      HCT116 human colon carcinomas, wild-type p53 (p53-WT) and complete knockout of
      p53 (p53-null) cells. Capsaicin and resveratrol, alone or in combination,
      inhibited cell growth and promoted apoptosis by the elevation of NO; combined
      treatment in p53-WT cells was most effective. Increased NO production after
      treatment uniformly stimulated p53 and Bax expression through Mdm2 down
      regulation in p53-WT cells, whereas all were unaffected in p53-null cells. Both
      cell types underwent a reduction in the levels of anti-apoptotic Bcl-2 protein,
      cytochrome c loss from mitochondria and activation of caspase 9 together with
      caspase 3, independently of p53 status. Concomitantly, we observed DR4, Fas(CD95)
      and caspase 8 activation, suggesting that these compounds activate both the
      mitochondrial and death receptor pathways working together to induce apoptosis.
      These findings provide insight into the mechanism of apoptotic action of
      capsaicin and resveratrol based on p53 status and indicate manipulation of NO may
      offer exciting opportunities to improve the effectiveness of colon cancer
      treatment.

PMID- 19846904
TI  - p53-Mediated down-regulation of the human DNA repair gene O6-methylguanine-DNA
      methyltransferase (MGMT) via interaction with Sp1 transcription factor.
AB  - O(6)-Methylguanine-DNA methyltransferase (MGMT), a ubiquitous DNA repair protein,
      reverses mutagenic and cytotoxic effects of O(6)-alkylguanine in DNA induced by
      chemotherapeutic N-alkyl N-nitrosourea and procarbazine type drugs by
      dealkylating the adduct. MGMT expression is down-regulated by wild-type p53
      (WTp53) in human tumor cells. Here we report that p53 sequesters the Sp1
      transcription factor to prevent its binding to the cognate cis elements in the
      MGMT promoter and thus inhibits MGMT expression. Sp1 overexpression abrogated the
      inhibitory effect of p53 on the MGMT promoter activity in a dose-dependent
      manner. Stable interaction of Sp1 with WTp53 was observed in HCT116 cells.
      Moreover, WTp53 overexpression reduced the binding of the nuclear extract to the
      Sp1 consensus sequence, even though recombinant p53 alone did not bind to the
      same sequence. Taken together, these results suggest that sequestration of Sp1
      could be one of the mechanisms by which p53 negatively regulates MGMT expression,
      thus enhancing sensitivity of tumor cells to O(6)-alkylguanine generating drugs.

PMID- 19846905
TI  - STX140 and STX641 cause apoptosis via the intrinsic mitochondrial pathway and
      down-regulate survivin and XIAP expression in ovarian and prostate cancer cells.
AB  - Many anticancer drugs target microtubules and induce apoptosis. However, improved
      microtubule-targeting drugs, such as STX140 and STX641, are being developed.
      These compounds induce cell cycle arrest and apoptosis in a variety of tumour
      cells. The mechanisms that induce apoptosis and the key mediators involved are
      elucidated in this study. Results demonstrate that STX140 and STX641 depolarise
      mitochondrial bioenergetics and activate caspase 3/7 in A2780, LNCaP and MCF-7
      cancer cells. Furthermore, both compounds cause a significant reduction in the
      expression of survivin and XIAP. This work details the temporal organisation of
      apoptosis induced by two microtubule disruptors and highlights the role that the
      down-regulation of survivin and XIAP may play in this process.

PMID- 19846906
TI  - Role of MGMT in tumor development, progression, diagnosis, treatment and
      prognosis.
AB  - O(6)-Methylguanine-DNA-methyltransferase (MGMT) is a unique protein, which both
      repairs O(6)-alkylguanine lesions stoichiometrically without a multi-enzymatic
      pathway and self-inactivates. It has recently been linked to the therapeutic
      success of alkylating agent chemotherapy, specifically temozolomide treatment.
      This drug affects the MGMT pathway to induce cell death in tumor tissue. Low
      levels of functional MGMT have been correlated with success of treatment, while
      high levels bring about failure of therapy. Expression of MGMT protein varies in
      normal and tumoral tissue. Furthermore, its epigenetic silencing due to promoter
      methylation has been linked to its lack of expression in many types of tumor,
      including gliomas. Great enthusiasm surrounds the utility of this protein in
      cancer treatment. Not only has there been success in manipulating MGMT levels to
      enhance alkylating agent therapy, but studies also suggest a possible role of
      MGMT in protecting hematopoietic cells from the myelosuppressive effects of high
      dose chemotherapy. Innovative research into this protein will no doubt be
      rewarding. This review presents a summary of what is known about this unique
      protein, including its structure, function in its pathway, polymorphisms,
      expression in normal and tumoral tissue, relation to alkylating agent therapy,
      and possible future applications.

PMID- 19846907
TI  - Cyclin-mediated G1 arrest by celecoxib differs in low-versus high-grade bladder
      cancer.
AB  - BACKGROUND: Celecoxib and other non-steroidal anti-inflammatory drugs (NSAIDs)
      are being evaluated in the prevention of bladder and other cancers. Here we
      investigate molecular effects of celecoxib independent of cyclooxygenase (COX)-2
      expression levels in urothelial carcinoma of the bladder. MATERIALS AND METHODS:
      Low-grade RT-4 and high-grade UM-UC-3 bladder cancer cells were treated with 0-50
      muM celecoxib. Growth, cell cycle and apoptosis were measured by crystal violet
      elution and flow cytometry. Western analysis was performed for COX-2, Rb, cyclin
      B1/D1, and phospho-cyclin B1/D1. COX-2 induction was achieved with phorbol ester.
      RESULTS: Celecoxib inhibited growth of RT-4 and UM-UC-3, with G(1) cell cycle
      arrest and altered cyclin B1/D1 expression in RT-4, whereas Rb up-regulation
      occurred in UM-UC-3. Apoptosis occurred in both cell lines. CONCLUSION: Celecoxib
      induces G(1) cell cycle arrest in low- and high-grade bladder cancer by different
      pathways. This heterogeneous molecular response supports combination approaches
      to prevention and treatment.

PMID- 19846908
TI  - In vivo imaging of human colorectal cancer using radiolabeled analogs of the
      uroguanylin peptide hormone.
AB  - BACKGROUND: Uroguanylin is an endogenous peptide agonist that binds to the
      guanylate cyclase C receptor (GC-C). GC-C is overexpressed in human colorectal
      cancer (CRC), and exposure of GC-C-expressing cells to GC-C agonists results in
      cell cycle arrest and/or apoptosis, highlighting the therapeutic potential of
      such compounds. This study describes the first use of radiolabeled uroguanylin
      analogs for in vivo detection of CRC. MATERIALS AND METHODS: The peptides
      uroguanylin and E(3)-uroguanylin were N-terminally labeled with the DOTA
      chelating group via NHS ester activation and characterized by RP-HPLC, ESI-MS,
      and GC-C receptor binding assays. The purified conjugates were radiolabeled with
      In-111 and used for in vivo biodistribution and SPECT imaging studies. In vivo
      experiments were carried out using SCID mice bearing T84 human colorectal cancer
      tumor xenografts. RESULTS: Alteration of the position 3 aspartate residue to
      glutamate resulted in increased affinity for GC-C, with IC(50) values of 5.0+/
      0.3 and 9.6+/-2.9 nM for E(3)-uroguanylin and DOTA-E(3)-uroguanylin,
      respectively. In vivo, (111)In-DOTA-E(3)-uroguanylin demonstrated tumor uptake of
      1.17+/-0.23 and 0.61+/-0.07% ID/g at 1 and 4 h post injection, respectively. The
      specificity of tumor localization was demonstrated by coinjection of 3 mg/kg
      unlabeled E(3)-uroguanylin, which reduced tumor uptake by 69%. Uptake in kidney,
      however, was dramatically higher for the uroguanylin peptides than for previously
      characterized radiolabeled E. coli heat-stable enterotoxin (STh) analogs
      targeting GC-C, and was also inhibited by coinjection of unlabeled peptide in a
      fashion not previously observed. CONCLUSION: Use of uroguanylin-targeting vectors
      for in vivo imaging of colorectal cancers expressing GC-C resulted in tumor
      uptake that paralleled that of higher affinity heat-stable enterotoxin peptides,
      but also resulted in increased kidney uptake in vivo.

PMID- 19846909
TI  - The expression and function of IGFBP-3 in normal and malignant breast tissue.
AB  - The mitogenic and anti-apoptotic effects of insulin-like growth factor-I (IGF-I)
      are regulated by a family of insulin-like growth factor binding proteins
      (IGFBPs), particularly IGFBP-3. Little is known about the IGF-independent role of
      IGFBP-3 in breast cancer and the mechanisms regulating its production. The
      expression of IGFBP-3 in paired malignant and adjacent normal (n=53), and healthy
      normal (n=17) breast tissue samples was investigated using RT-PCR,
      immunohistochemistry and ELISA. We compared IGFBP-3 expression with other members
      of the IGF-I axis, other known tumorigenic genes and clinicopathological
      parameters. We also developed a novel tissue explant system using fresh normal
      and malignant breast tissue, with which we examined the in vitro effects of IGFBP
      3 alone and in combination with known apoptotic agent, doxorubicin (n=6), on
      tissue viability and apoptosis. We demonstrated a high level of expression of
      IGFBP-3 mRNA in all samples. 96% of samples also expressed IGFBP-3 protein. No
      significant correlation was seen between IGFBP-3 expression and other
      clinicopathological parameters. The in vitro tissue explant system demonstrated
      that IGFBP-3 had little effect by itself on apoptosis. However, when used in
      combination with doxorubicin, increased apoptosis was seen in tumours. In
      contrast, less apoptosis was seen in normal tissue suggesting a protective
      effect. These divergent effects suggest a potential novel chemotherapeutic
      approach in the treatment of breast cancer. These findings suggest that IGFBP-3
      may play a role in tumorigenesis, and that IGFBP-3 levels could be used in the
      future in cancer risk assessment/prevention or as markers of response to cancer
      treatments.

PMID- 19846910
TI  - Potent inhibition of tubulin polymerisation and proliferation of paclitaxel
      resistant 1A9PTX22 human ovarian cancer cells by albendazole.
AB  - BACKGROUND: Resistance to paclitaxel (PTX) is a major concern in treating ovarian
      cancer. Thus, agents effective in taxane-resistant tumours are highly sought. It
      has recently been shown that albendazole (ABZ) is a potent inhibitor of cell
      proliferation, angiogenesis and tumour growth. This study was designed to examine
      the efficacy of ABZ in PTX-resistant human ovarian cancer 1A9PTX22 cells.
      MATERIALS AND METHODS: Using both the parent PTX-sensitive 1A9 and PTX-resistant
      sub-line 1A9PTX22 cells, the effects of both drugs on cell proliferation, tubulin
      polymerisation and microtubule distribution across the cell was investigated.
      RESULTS: Comparison of the inhibitory concentration to achieve 50% cell death
      (IC(50)) revealed that, unlike PTX, ABZ is highly efficacious in inhibiting
      proliferation of 1A9PTX22 cells. The finding that ABZ but not PTX is highly
      effective in disrupting tubulin polymerisation in these cells confirmed
      involvement of the tubulin pathway. CONCLUSION: Data from this study suggest that
      ABZ is effective in suppressing growth of PTX-resistant ovarian tumour cells.

PMID- 19846911
TI  - Xanthohumol activates the proapoptotic arm of the unfolded protein response in
      chronic lymphocytic leukemia.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is an incurable disease with a
      natural history of increasing resistance to chemotherapy. A novel approach to
      overcome chemotherapy resistance may be targeting the endoplasmic reticulum (ER).
      PATIENTS AND METHODS: The involvement of the unfolded protein response (UPR) in
      the cell killing effect of xanthohumol (X) was examined in 18 patient samples.
      RESULTS: X-induced apoptosis of CLL cells was accompanied by the induction of
      glucose-regulated protein of 78 kDa (GRP78) and heat-shock protein of 70 kDa
      (Hsp70) protein levels and by sustained phosphorylation of the eukaryotic
      translation initiation factor 2 (eIF2alpha), suggesting the involvement of the ER
      stress transducer, the double-stranded RNA-activated protein kinase (PKR)-like ER
      kinase (PERK). The X-box-binding protein 1 (XBP1) mRNA was spliced but no clear
      activation of activating transcription factor 6 (ATF6) was observed. The
      proapoptotic outcome was further demonstrated by the up-regulation of
      CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), down-regulation
      of myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2), cleavage of
      poly-(ADP)-ribose polymerase (PARP) and processing of caspase-3, -4 and -9.
      Furthermore, X showed proteasome inhibitory activity. CONCLUSION: X stimulates
      the proapoptotic arm of the UPR in ex vivo CLL cells, suggesting that ER stress
      may play an important role during X-induced apoptosis.

PMID- 19846912
TI  - Artemisinin-transferrin conjugate retards growth of breast tumors in the rat.
AB  - BACKGROUND: Artemisinin is a compound isolated from the wormwood Artemisia annua
      L. It reacts with iron and forms cytotoxic free radicals. It is selectively more
      toxic to cancer than normal cells because cancer cells contain significantly more
      intracellular free iron. Previously, we found that covalently tagging artemisinin
      to transferrin enhanced the selectivity and toxicity of artemisinin toward cancer
      cells in vitro. In the present research, artemisinin-transferrin conjugate was
      tested in a rat breast cancer model. MATERIALS AND METHODS: Breast tumors were
      induced in rats by subcutaneous implantation of rat MTLn3 breast cancer cells.
      Once tumors were formed, daily intravenous injections of artemisinin-transferrin
      conjugate were administered. RESULTS: The conjugate significantly retarded the
      growth rate of breast tumors in the rat. No significant side effect was observed
      in the rats during treatment. CONCLUSION: Artemisinin-transferrin conjugate could
      be developed into a potent therapeutic agent for cancer in humans.

PMID- 19846913
TI  - Exogenous expression of caspase-14 induces tumor suppression in human salivary
      cancer cells by inhibiting tumor vascularization.
AB  - BACKGROUND: Current therapeutic approaches to salivary gland cancer are often
      associated with severe disfigurement and loss of glandular function, which are
      traumatic to the patients. Exploration of novel treatment approaches, such as
      gene therapy, is needed. MATERIALS AND METHODS: The human salivary gland cancer
      cell line HSG was transiently transfected with full length human caspase-14 cDNA.
      Photomicroscopy, BrdU assay, cell counting, MTT assay, and TUNEL assay were
      applied. To determine the tumorigenicity, tumor volume, tumor pathology and
      vascularization were analyzed in vivo. RESULTS: Cell growth and viability were
      inhibited significantly by transient caspase-14 expression. Caspase-14 expression
      resulted in a significant reduction of tumorigenicity. Importantly, a significant
      decrease in tumor blood vessel formation was observed. CONCLUSION: Salivary gland
      cancer cells underwent growth inhibition, cell death, and reduced tumorigenicity
      in vivo when exogenous caspase-14 was expressed, which could be due, in part, to
      an inhibitory effect of caspase-14 on tumor vascularization.

PMID- 19846914
TI  - Down-regulation of 20-HETE synthesis and signaling inhibits renal adenocarcinoma
      cell proliferation and tumor growth.
AB  - BACKGROUND: We examined the ability of inhibitors of the synthesis or actions of
      20-HETE, metabolite of arachidonic acid, to inhibit proliferation of human renal
      carcinoma cell lines. MATERIALS AND METHODS: 786-O and 769-P cells were exposed
      to either 10 microM HET0016 (selective inhibitor of 20-HETE synthesis), 10 microM
      WIT002 (20-HETE antagonist), or vehicle. Subsequently, we assessed the effect of
      WIT002 on tumor growth in vivo using an ectopic mouse model of clear-cell renal
      carcinoma. RESULTS: Addition of HET0016 and WIT002 inhibited the proliferation of
      786-O and 769-P human renal cell carcinoma lines. HET0016 and WIT002 had little
      effect on the proliferation of primary cultures of normal human proximal tubule
      epithelial cells. WIT002 (10 mg/kg, s.c.) administered daily to athymic nude mice
      implanted subcutaneously with 786-O cells reduced the growth of the tumors by 84
      % compared to vehicle (p<0.001). CONCLUSION: 20-HETE is required for
      proliferation of human renal epithelial cancer.

PMID- 19846916
TI  - Telomeres and telomerase in sarcomas.
AB  - Telomeres of human tumor cells have two types of telomere maintenance mechanisms
      by telomerase activation and alternative lengthening of telomeres (ALT). Although
      over 80% of all carcinomas rely on telomerase activity to maintain stable
      telomere length, many types of sarcoma elongate telomeres consistent with ALT in
      the absence of telomerase activity. Recently, the presence of telomerase activity
      and ALT in several sarcomas was examined extensively, and recent studies indicate
      a positive correlation between the telomere maintenance mechanism and tumor
      aggressiveness in several sarcoma types. We reviewed both the activation of
      telomere maintenance in a variety of common bone and soft tissue sarcoma
      subtypes, and the consequences of telomere maintenance mechanisms with respect to
      the clinical characteristics.

PMID- 19846915
TI  - Tetraidothyroacetic acid (tetrac) and tetrac nanoparticles inhibit growth of
      human renal cell carcinoma xenografts.
AB  - Renal cell carcinoma is the most lethal of the common urologic malignancies, with
      no available effective therapeutics. Tetrac (tetraiodothyroacetic acid) is a
      deaminated analogue of L-thyroxine (T(4)) that blocks the pro-angiogenesis
      actions of T(4) and 3, 5, 3'-triiodo-L-thyronine as well as other growth factors
      at the cell surface receptor for thyroid hormone on integrin alphavbeta3. Since
      this integrin is expressed on cancer cells and also on endothelial and vascular
      smooth cells, the possibility exists that Tetrac may act on both cell types to
      block the proliferative effects of thyroid hormone on tumor growth and tumor
      related angiogenesis. To test this hypothesis, we determined the effect of Tetrac
      on tumor cell proliferation and on related angiogenesis of human renal cell
      carcinoma (RCC). We used two models: tumor cell implants in the chick
      chorioallantoic membrane (CAM) system and xenografts in nude mice. To determine
      the relative contribution of the nuclear versus the plasma membrane action of
      Tetrac, we compared the effects of unmodified Tetrac to Tetrac covalently linked
      to poly (lactide-co-glycolide) as a nanoparticle (Tetrac NP) that acts
      exclusively at the cell surface through the integrin receptor. In the CAM model,
      Tetrac and Tetrac NP (both at 1 microg/CAM) arrested tumor-related angiogenesis
      and tumor growth. In the mouse xenograft model, Tetrac and Tetrac NP promptly
      reduced tumor volume (p<0.01) when administered daily for up to 20 days. Animal
      weight gain was comparable in the control and treatment groups. Overall, the
      findings presented here provide evidence for the anti-angiogenic, and anti-tumor
      actions of Tetrac and Tetrac NP and suggest their potential utility in the
      treatment of renal cell carcinoma.

PMID- 19846917
TI  - The effect of MAPK inhibitors on arsenic trioxide-treated Calu-6 lung cells in
      relation to cell death, ROS and GSH levels.
AB  - Arsenic trioxide (ATO) can regulate many biological functions such as apoptosis
      and differentiation. We recently demonstrated that ATO-induced apoptosis in Calu
      6 lung cancer cells is correlated with glutathione (GSH) content. Here, the
      effects of ATO and/or mitogen-activated protein kinase (MAPK) inhibitors on Calu
      6 cells were investigated in relation to cell growth, cell death, reactive oxygen
      species (ROS) and GSH levels. Treatment with ATO inhibited the growth of the Calu
      6 cells at 72 hours. ATO induced apoptosis, which was accompanied by the loss of
      mitochondrial membrane potential (MMP; DeltaPsi(m)). While general nonspecific
      ROS decreased in the ATO-treated Calu-6 cells, the intracellular superoxide anion
      (O(2)(-)) level including mitochondrial O(2)(-) increased. ATO also induced GSH
      depletion in the Calu-6 cells. The treatment with MAP kinase kinase (MEK), c-Jun
      N-terminal kinase (JNK) and p38 inhibitors intensified the cell growth
      inhibition, cell death, MMP (DeltaPsi(m)) loss, and GSH depletion in the ATO
      treated Calu-6 cells. In addition, the JNK and p38 inhibitors significantly
      increased the ROS levels including O(2)(-) in the ATO-treated Calu-6 cells. In
      conclusion, all the MAPK inhibitors slightly intensify cell death in the ATO
      treated Calu-6 cells and the changes of ROS and GSH brought about by ATO and/or
      MAPK inhibitor treatment partially influence cell growth and death in Calu-6
      cells.

PMID- 19846918
TI  - Antitumor efficacy and molecular mechanism of TLK58747, a novel DNA-alkylating
      prodrug.
AB  - BACKGROUND: DNA-damaging agents are widely used for the treatment of human
      malignancies. Agents containing the multifunctional alkylating moiety tetrakis(2
      chloroethyl)phosphorodiamidic acid are currently under development as cancer
      therapeutics. MATERIALS AND METHODS: TLK58747, a phophorodiamidate-based prodrug,
      was tested in vivo for antitumor efficacy and safety. The in vitro responses of
      tumor cells to TLK58747 were examined by cytotoxicity assays, cell cycle
      analysis, immunoblots and microscopy. RESULTS: TLK58747 was efficacious in
      xenograft models of human breast, pancreas, and prostate cancer, as well as in
      leukemia and glioma. It caused less bone marrow suppression in rats than did
      cyclophosphamide. In vitro, TLK58747 inhibited the growth of a wide variety of
      cancer cells and activated the DNA damage-response pathway, leading to G(2)/M
      cell cycle arrest and subsequent premature senescence or apoptosis. CONCLUSION:
      TLK58747 is a promising new alkylating agent with broad antitumor activity and
      superior safety that warrants further development.

PMID- 19846919
TI  - Inhibitory effect of cordycepin on hematogenic metastasis of B16-F1 mouse
      melanoma cells accelerated by adenosine-5'-diphosphate.
AB  - Platelet aggregation induced by cancer cells is an indispensable step for
      hematogenic metastasis. In these studies, we investigated whether platelet
      aggregation accelerates hematogenic metastasis of cancer cells in mice and the
      effect of cordycepin (3'-deoxyadenosine), a component of Cordyceps sinensis, on
      hematogenic metastasis accelerated by adenosine-5'-diphosphate (ADP). ADP
      significantly increased the number of metastatic lung nodules in mice injected
      intravenously with B16-F1 mouse melanoma cells (B16-F1 cells) in a dose-dependent
      manner and cordycepin significantly reduced the number of metastatic nodules of
      B16-F1 cells formed in the lung accelerated by ADP injected simultaneously with
      B16-F1 cells. These results suggest that ADP accelerated hematogenic metastasis
      and cordycepin has an inhibitory effect on hematogenic metastasis of B16-F1
      melanoma cells via blocking of ADP-induced platelet aggregation in vivo.

PMID- 19846920
TI  - Expression of M-CSF and CSF-1R is correlated with histological grade in soft
      tissue tumors.
AB  - BACKGROUND: Macrophage colony stimulating factor (M-CSF) binds to colony
      stimulating factor-1 receptor (CSF-1R) and thereby stimulates the proliferation,
      differentiation and behaviour of monocytes, macrophages and their bone marrow
      progenitors. Previous studies have suggested that high expression of these
      markers is correlated with poor prognosis. MATERIALS AND METHODS: M-CSF, CSF-1R
      and CD68 protein expression was examined by immunohistochemistry in paraffin
      embedded sections of soft tissue tumor specimens from 46 patients. The proportion
      of positive cells and the expression intensity of M-CSF, CSF-1R and CD68 in both
      the tumor cell areas and the adjacent stromal areas were correlated to the
      histological grade. RESULTS: In the high grade tumors M-CSF and CSF-1R were more
      highly expressed than in the low grade tumors. This was seen in both the tumor
      cell areas and the adjacent stromal areas. No differences in CD68 expression
      between the high and low grade tumors were found either in the tumor cell areas
      or the stromal areas. CONCLUSION: The expression of M-CSF and CSF-1R in tumor
      cell areas and adjacent stromal areas correlate with the histological grade of
      soft tissue tumors.

PMID- 19846921
TI  - Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres
      for cancer therapy.
AB  - BACKGROUND: Among the potent anticancer agents, curcumin has been found to be
      very efficacious against many different types of cancer cells. However, the major
      disadvantage associated with the use of curcumin is its low systemic
      bioavailability when administered orally due to its poor aqueous solubility. Our
      present work investigated the efficiency of encapsulation of curcumin in poly
      (lactic-coglycolic acid) (PLGA) nanospheres using solid/oil/water emulsion
      solvent evaporation method. MATERIALS AND METHODS: The nanospheres were
      formulated and then characterized for percent yield, encapsulation efficiency,
      surface morphology, particle size, drug distribution studies, drug polymer
      interaction studies and in vitro drug release profiles. RESULTS: Our studies
      showed the successful formation of smooth and spherical curcumin-loaded PLGA
      nanospheres, with an encapsulation efficiency of 90.88+/-0.14%. The particle size
      distribution showed a range of 35 nm to 100 nm, with the mean particle size being
      45 nm. Evaluation of these curcumin-loaded nanospheres was carried out in
      prostate cancer cell lines. Results showed robust intracellular uptake of the
      nanospheres in the cells. Cell viability studies revealed that the curcumin
      loaded nanospheres were able to exert a more pronounced effect on the cancer
      cells as compared to free curcumin. CONCLUSION: Our studies achieved successful
      formulation of curcumin loaded PLGA nanospheres, thus indicating that
      nanoparticle-based formulation of curcumin has high potential as an adjuvant
      therapy for clinical application in prostate cancer.

PMID- 19846922
TI  - Infiltration by macrophages and lymphocytes in transplantable mouse sarcoma after
      irradiation with high-intensity focused ultrasound.
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) therapy offers great promise
      for the treatment of cancer. The histological changes, including the antitumor
      immunological response, after HIFU treatment was examined in soft tissue sarcoma.
      MATERIALS AND METHODS: Sarcoma 180 cells were injected subcutaneously in mice.
      Approximately 2 weeks after the injection, the tumor was irradiated by a single
      shot of HIFU. The tumor diameter was measured and the survival rate was observed
      after treatment. The tumors were resected, and stained with TUNEL stain, tartrate
      resistant acid phosphatase (TRAP) stain to detect tumor-associated macrophages,
      and immunohistochemical stains for CD4 and CD8. RESULTS: The tumor size in the
      HIFU group was significantly smaller than the control and survival rate was
      significantly higher. The numbers of TUNEL-, TRAP-, CD4- and CD8-positive cells
      infiltrating the tumor were significantly higher in the HIFU group. CONCLUSION:
      HIFU, even when administered as a single shot, induces apoptosis of tumor cells
      and intratumoral infiltration of macrophages and lymphocytes.

PMID- 19846923
TI  - c-FLIP gene silencing eliminates tumor cells in breast cancer xenografts without
      affecting stromal cells.
AB  - Cellular FLICE-like inhibitory protein (c-FLIP) is an inhibitor of death receptor
      mediated apoptosis and exerts its anti-apoptotic function by blocking the
      activation of caspase-8. We recently showed that the siRNA-mediated knockdown of
      c-FLIP in MCF-7 breast cancer cells growing in vitro triggered apoptosis. The aim
      of this study was to determine if the in vivo knockdown of c-FLIP in MCF-7 breast
      cancer xenografts affected tumor viability. Immunohistochemical detection of c
      FLIP in the tumor sections revealed that the knockdown of c-FLIP eliminated the
      neoplastic cells within the breast cancer xenografts without affecting the normal
      stromal and fibroblastic cells. These results indicate that c-FLIP is required
      for breast cancer growth and is a relevant therapeutic target for the treatment
      of breast cancer.

PMID- 19846924
TI  - The expression of MT1 melatonin receptor and Ki-67 antigen in melanoma malignum.
AB  - BACKGROUND: Melatonin, the principal hormone produced by the pineal gland,
      manifests strong potency of inhibiting growth of dermal melanoma cells both under
      in vitro and in vivo conditions. Although the mechanism of the phenomenon has not
      been fully clarified yet, melatonin receptors seem to play a key role in the
      inhibition. In humans, two main types of high affinity membrane melatonin
      receptors have been identified, including MT1 (Mel1a) and MT2 (Mel1b) receptors,
      and their expression increases efficacy of the oncostatic melatonin activity. The
      principal aim of this study involved determination of location and intensity of
      expression of MT1 melatonin receptors and of Ki-67 proliferation-associated
      antigen in dermal melanoma using an immunohistochemical technique and an
      examination of their reciprocal correlation and their relationship with clinical
      advancement of the tumour, i.e. with its depth of infiltration. PATIENTS AND
      METHODS: Immunohistochemical studies were conducted on the material of 48 cases
      of dermal melanoma, including 38 primary tumours and 10 metastatic lymph nodes,
      fixed in formalin and embedded in paraffin. RESULTS: In all the examined cases,
      positive immunohistochemical reactions were obtained with antibodies to MT1 and
      Ki-67. Expression of MT1 receptor was more pronounced in primary tumours than in
      lymph nodes (p<0.05). Depth of tumour infiltration demonstrated a moderate
      positive correlation with the intensity of MT1 expression (r=0.45; p<0.05) and a
      strongly positive correlation with the expression of Ki-67 antigen (r=0.79;
      p<0.05). Moreover, both in primary tumours and in metastatic lymph nodes, a weak
      correlation was detected between the expression of MT1 receptor and expression of
      Ki-67 antigen. CONCLUSION: Confirmation of positive correlation between the
      expression of MT1 receptor and depth of melanoma infiltration may point to future
      use of MT1 as a prognostic index for such tumours.

PMID- 19846925
TI  - Association of genetic polymorphisms of EXO1 gene with risk of breast cancer in
      Taiwan.
AB  - The aim of the present study was to evaluate the association between the
      polymorphisms of the EXO1 gene and the risk of breast cancer in central Taiwan.
      PATIENTS AND METHODS: In this hospital-based study, the association of EXO1
      A1419G (rs3754093), C908G (rs10802996), A238G (rs1776177), C498T (rs1635517),
      K589E (rs1047840), G670E (rs1776148), C723R (rs1635498), L757P (rs9350) and
      C3114T (rs851797) polymorphisms with breast cancer risk in a central Taiwanese
      population was investigated. In total, 1,272 patients with breast cancer and
      1,272 age- and gender-matched healthy controls recruited from the China Medical
      University Hospital were genotyped. RESULTS: A significantly different
      distribution was found in the frequency of the EXO1 K589E genotype, but not the
      other genotypes, between the breast cancer and control groups. The A allele EXO1
      K589E conferred a significantly (p=0.000025) increased risk of breast cancer. As
      for the rest of the polymorphisms, there was no difference in distribution
      between the breast cancer and control groups. CONCLUSION: Our results provide
      evidence that the A allele of EXO1 K589E may be associated with the development
      of breast cancer and may be a useful biomarker for breast cancer detection and
      primary prevention.

PMID- 19846926
TI  - Significant association of XPD codon 312 single nucleotide polymorphism with
      bladder cancer susceptibility in Taiwan.
AB  - BACKGROUND: The DNA repair gene xeroderma pigmentosum group D (XPD), an important
      caretaker of the overall genome stability, is thought to play a major role in the
      development of human malignancy. Polymorphic variants of XPD, at codon 312
      (rs1799793), 751 (rs13181) and promoter-114 (rs3810366), were chosen to be
      studied for their association with bladder cancer susceptibility in a central
      Taiwanese population. PATIENTS AND METHODS: In this hospital-based case-control
      study, bladder cancer patients (308) and age- and gender-matched healthy controls
      (308) were recruited and their genotypes were analyzed by a polymerase chain
      reaction-based restriction fragment length polymorphism (PCR-RFLP) method.
      RESULTS: A significant difference in the frequency of the XPD codon 312 genotype,
      but not the XPD codon 751 or promoter-114 genotypes, was found between the
      bladder cancer and control groups. Those who had G/A or A/A at XPD codon 312
      showed a 1.85-fold (95% confidence interval=1.34-2.56) increased risk of bladder
      cancer compared to those with G/G. As for XPD codon 312 and promoter-114, there
      was no difference in distribution between the bladder cancer and control groups.
      CONCLUSION: The heterozygous and homozygous A allele of the XPD codon 312 may be
      responsible for bladder carcinogenesis and useful in the early detection and
      prediction of bladder cancer.

PMID- 19846927
TI  - Clusterin overexpression and relapse-free survival in breast cancer.
AB  - BACKGROUND: The prognostic significance of the antiapoptotic protein secretory
      clusterin overexpression in breast cancer is unclear. PATIENTS AND METHODS:
      Secretory clusterin expression was explained in three hundred and fifty-two
      patients with breast cancer by immunohistochemistry. Clusterin overexpression was
      tested for correlation with overall survival (OS) and relapse-free survival
      (RFS). RESULTS: The overall frequency of clusterin overexpression was 52% (178
      out of 342) in breast cancer; 44% for in situ carcinomas and 53% for invasive
      cancer. Among fifty-six patients with tumor recurrence, clusterin overexpression
      was found in 74% (14 out of 19) in breast cancer <T2 stage and 51% (19 out of 37)
      in >or=T2 stage breast cancer. The Kaplan-Meier analysis revealed that clusterin
      overexpression was a prognostic factor for RFS in breast cancer <T2 stage (mean
      RFS, 79.8 vs. 73.5 months, p=0.044). CONCLUSION: Our results suggest that
      clusterin overexpression might be a predictive factor for recurrence in <T2 stage
      breast cancer.

PMID- 19846928
TI  - PTP4A3 expression increases strongly in lymph node metastases from colorectal
      carcinoma.
AB  - BACKGROUND: Numerous studies have proven that protein tyrosine phosphatase type
      IV A member 3 (PTP4A3) plays a significant role in local lymph node metastasis
      from colorectal carcinoma. The aim of the current study was to assess PTP4A3
      expression in colorectal carcinomas and lymph nodes in correlation with chosen
      anatomoclinical parameters. PATIENTS AND METHODS: Forty-nine patients were
      analyzed with respect to age, tumor location, pTN stage and local lymph node
      involvement. The level of PTP4A3 expression was determined immunohistochemically
      using mouse monoclonal anti- PTP4A3 antibody (monoclonal antibody 3B6, anti-human
      PTP4A3 from Attogen Biomedical Research, USA). RESULTS: Positive reaction for
      PTP4A3 in the main tumor mass was observed in 9/49 (18.4%) cases, whereas in
      metastatic lymph nodes in 22/24 (91.6%) cases. Statistical analysis showed no
      correlation of PTP4A3 expression in the main tumor mass with such clinical
      parameters as age, location, histological type or lymph node involvement.
      Moreover the expression of PTP4A3 in the main tumor mass was not associated with
      the expression of this protein in lymph node metastases. However, there was a
      statistically significant correlation between lymph node involvement and PTP4A3
      expression in lymph node metastases. CONCLUSION: The role of the PTP4A3 has not
      yet been fully elucidated. Our finding indicate PTP4A3 is strongly expressed in
      colorectal carcinoma metastases of the lymph nodes although the significance of
      this is unclear.

PMID- 19846929
TI  - The effect of a novel botanical agent TBS-101 on invasive prostate cancer in
      animal models.
AB  - BACKGROUND: Traditional Botanical Supplement-101 (TBS-101) is a newly developed
      proprietary botanical agent containing seven standardized botanical extracts,
      including: Panax ginseng, cranberry, green tea, grape skin, grape seed, Ganoderma
      lucidum and chamomile. Each of the components has been consumed either in the
      regular diet or as natural supplement. When used as a single agent, each of these
      seven botanicals has been implicated in chemoprevention and therapy in various
      types of cancer. The anticancer effect of TBS-101, with the specific combination
      of these anti-cancer botanicals for the treatment of prostate cancer (PCa), has
      not been tested. MATERIALS AND METHODS: The IC(50) and the effect of TBS-101 on
      the proliferation and apoptosis of PC-3 cells were determined. Tumor xenograft
      mice were generated by subcutaneously implanting PC-3 cells into mice and tumors
      were allowed to grow to different sizes before starting the treatment. The
      effects of TBS-101 on tumor growth were assessed by measuring tumor size and by
      histological, pathological and immunohistochemical analyses. A basic toxicity
      study was performed to test the tolerance of the mice to high doses of TBS-101.
      RESULTS: Treatment of the PC-3 cells with TBS-101 resulted in a dose-dependent
      inhibition of cell growth, with an IC(50) of 1.4 microg/ml. A concomitant
      induction of apoptosis in PC-3 cells treated with TBS-101 was also observed. Upon
      the treatment with TBS-101, all three groups of mice bearing moderate or large
      tumors showed significant inhibition of tumor growth and invasion. In contrast,
      control mice treated with vehicle alone had significant tumor growth and lymph
      node metastasis. In the basic toxicity studies, high doses of TBS-101 exerted no
      toxicity in healthy or tumor-bearing mice. CONCLUSION: The natural botanical
      agent TBS-101 has a good safety profile and significant anticancer activities in
      hormone-refractory PC-3 cells and large aggressive PC-3 tumors in a xenograft
      mouse model and has great potential for the treatment of aggressive prostate
      cancer.

PMID- 19846930
TI  - Effects of 5-FU on DNA synthesis and cytotoxicity of human lymphocytes induced by
      IL-2, TGF-beta3 and PGE2.
AB  - BACKGROUND: Low 5-fluorouracil (5-FU) concentrations cause a significant increase
      in DNA synthesis in mitogen-activated human lymphocytes. MATERIALS AND METHODS:
      We explored 2.5 microM 5-FU-induced DNA synthesis by testing 5-FU activity in
      hypoxanthine-aminopterin-thymidine (HAT)-containing medium, and its effect on
      thymidylate synthase (TS) activity and CD25 expression in interleukin (IL)-2
      activated human peripheral blood mononuclear cells (PBMCs) and the combined
      effects with prostaglandin E(2) (PGE(2)) and transforming growth factor (TGF)
      beta3. RESULTS: The co-stimulatory effect of 2.5 microM 5-FU on DNA synthesis was
      abrogated in HAT-cultured medium. 5-FU substantially reduced TS activity by 50%
      in IL-2-activated PBMCs. 5-FU combined with TGF-beta3 and PGE(2) did not alter
      their inhibitory effects on IL-2-activated natural killer cell cytotoxicity, but
      substantially affected increased DNA synthesis of cells cultured in IL-2 and co
      cultured with 10 ng/ml TGF-beta3 and 10 microM PGE(2). CONCLUSION: Low 5-FU
      concentrations increase DNA synthesis in lymphocytes and exert a co-stimulatory
      activity on TGF-beta3 and PGE(2) modulation of IL-2-activated lymphocytes.

PMID- 19846931
TI  - Cisplatin and oxaliplatin cytotoxic effects in sensitive and cisplatin-resistant
      human cervical tumor cells: time and mode of application dependency.
AB  - BACKGROUND: Time-dependence of cisplatin (CDDP) and oxaliplatin (L-OHP) cytotoxic
      effects in A431 and A431/Pt cells (sensitive and CDDP-resistant human cervical
      tumor cells) were investigated. MATERIALS AND METHODS: The drug application modes
      were pulse (12.5, 25 or 50 microM up to 72 h) and pulse-plus-chase (50 microM for
      2, 4 or 6 h, followed by washing and 72 h-incubation in drug-free medium).
      RESULTS: In the A431 cells, the pulse drug application showed time-effect curves
      with two plateaux; the inhibitory activity of CDDP was higher than that of L-OHP.
      The same growth-inhibition fraction was reached by L-OHP in a longer time than
      CDDP. In the A431/Pt cells, the curve shapes for both drugs were similar in both
      application modes and had the same general characteristics, noted in the parental
      cell line. CDDP appeared less active than L-OHP. CONCLUSION: Different
      cytotoxicity curves of Pt-drugs could be dictated by the presence of the bulky
      diaminocyclohexane (DACH) ligand, affecting the kinetics of Pt-DNA binding;
      mismatch repair (MSH2) protein is involved in the resistance.

PMID- 19846932
TI  - CDK10 is not a target for aberrant DNA methylation in breast cancer.
AB  - BACKGROUND: Loss of cyclin-dependent kinase (CDK) 10 expression may be an
      important mechanism of tamoxifen resistance and the 5' CpG island associated with
      the CDK10 gene has been suggested to be a target for aberrant methylation in
      breast cancer. PATIENTS AND METHODS: The methylation status of CDK10, RASSF1A
      (Ras association domain family 1A) and DAL-1 (differentially expressed in
      adenocarcinoma of the lung) was determined by means of methylation-specific PCR
      (MSP) in the formalin-fixed, paraffin-embedded (FFPE) surgical specimens of 96
      breast carcinoma patients. Reverse transcription kinetic PCR (RT-kPCR) was used
      for assessment of the expression of CDK10. RESULTS: The unmethylated form of
      CDK10, RASSF1A and DAL-1 was detected in all the samples analyzed. Methylation of
      the CDK10 5' region was not found in any of the 96 breast cancer samples. RASSF1A
      methylation was detected in 75 out of 96 (78%) and DAL-1 in 9 out of 15 (60%)
      breast cancer samples, respectively. Consistent with the methylation results, the
      expression of CDK10 was detected in all 96 samples. CONCLUSION: CDK10 is not a
      target for aberrant DNA methylation in breast cancer.

PMID- 19846933
TI  - Frequent CDH3 demethylation in advanced gastric carcinoma.
AB  - BACKGROUND: We recently found that CDH3 was frequently demethylated in advanced
      colorectal carcinomas. This prompted us to examine the demethylation status of
      the CDH3 gene in gastric carcinomas. MATERIALS AND METHODS: The demethylation
      status of the CDH3 gene was examined in primary tumors derived from 36 patients
      with gastric carcinoma using a quantitative methylation-specific PCR (qMSP) and
      was evaluated the correlation between the demethylation status and the
      clinicopathological findings. RESULTS: Demethylation of the CDH3 gene was
      detected in 25 out of the 36 (69%) primary gastric carcinomas, suggesting that
      the aberrant demethylation of CDH3 is a frequent event in gastric carcinomas.
      Demethylation of CDH3 was significantly associated with increasing TNM stage
      (p=0.0261). Moreover, a trend was shown toward infiltration beyond the serosa
      being associated with demethylation of CDH3 (p=0.0733). CONCLUSION: CDH3 was
      frequently demethylated in advanced gastric carcinomas.

PMID- 19846934
TI  - Decreased plasma ghrelin levels in patients with advanced cancer and weight loss
      in comparison to healthy individuals.
AB  - BACKGROUND: Ghrelin is a growth hormone-releasing acylated peptide found to be an
      appetite stimulant and low levels of it are detected in cachexia. The aim of the
      present study was to investigate the plasma ghrelin levels in cancer patients
      with a low performance status and weight loss and compare them with those of
      healthy individuals without weight loss. PATIENTS AND METHODS: Thirty patients
      (median age 65 years) with different malignancies, mainly pancreatic and gastric,
      and 27 healthy individuals (median age 62 years) were examined. The gender of
      both groups was well balanced. Plasma ghrelin was measured by a radioimmunoassay
      kit that uses a polyclonal antibody which recognizes the C-terminal of ghrelin.
      RESULTS: There was a statistically significant difference in the plasma ghrelin
      levels of the patients vs. the controls, with the patients having much lower
      levels (p<0.001). CONCLUSION: The notable reduction of ghrelin levels might be
      due to the severity and progression of the disease.

PMID- 19846935
TI  - Down-regulation of Tip60 gene as a potential marker for the malignancy of
      colorectal cancer.
AB  - BACKGROUND: Recently, it was shown that the loss of human Tip60 leads to an
      accumulation of double-strand DNA breaks and is linked to a growing number of
      cancer types. PATIENTS AND METHODS: Tip60 expression levels were in examined in
      38 colorectal cancer samples using a quantitative real-time polymerase chain
      reaction. Subsequently, clinicopathological data were correlated with the Tip60
      expression score. RESULTS: A down-regulation of the Tip60 gene was observed 5 out
      of 38 (13%) specimens of primary colorectal cancer. Tip60 down-regulation showed
      significant correlation with larger tumor size (p=0.0005), poorly differentiated
      type (p=0.0394), peritoneal dissemination (p=0.0053), distant metastasis
      (p=0.0394), and higher stage of TNM classification (p=0.0226). CONCLUSION: These
      results suggested that Tip60 was more frequently down-regulated in advanced
      colorectal carcinoma.

PMID- 19846936
TI  - Glutathione modulation reverses the growth-promoting effect of growth factors,
      improving the 5-fluorouracil antitumour response in WiDr colon cancer cells.
AB  - BACKGROUND: A common cause of treatment failure in colorectal cancer is
      chemoresistance, which may be related to the redox state of cancer cells and the
      tumour microenvironment, where growth factors (GFs) play an important role.
      Glutathione (GSH), a key regulator of the redox balance, is involved in GF
      signalling systems and may also protect against drug-induced cellular injury.
      MATERIALS AND METHODS: The effect of GSH modulation on 5-fluorouracil (5-FU)
      activity on the WiDr colon cancer cell line was studied. Cell proliferation and
      GSH content were assessed. Cells were exposed to the GSH modulators, L-buthionine
      SR-sulfoximine (BSO) or L 2 oxothiazolidine-4-carboxylate (OTZ), before treatment
      with 5-FU in the presence of hepatocyte growth factor (HGF), vascular endothelial
      growth factor (VEGF) or epidermal growth factor (EGF). RESULTS: Exposure to GFs
      significantly increased GSH levels and induced a pro-tumour effect. During the
      first 48 h of incubation, VEGF and EGF induced a near 30% reduction in 5-FU
      antitumour activity, while exposure to HGF abrogated the drug-induced growth
      inhibition. Treatment with OTZ and BSO abrogated the growth-promoting effects of
      GFs. Moreover, the addition of either of the GSH modulators to 5-FU produced an
      increase of nearly 40% in the 5-FU activity in the case of HGF or VEGF, and a 25%
      increase in the case of EGF. CONCLUSION: GSH manipulation could yield a
      therapeutic gain for chemotherapy with 5-FU in the presence of GFs.

PMID- 19846937
TI  - Transition of cleaved Notch1 and gene expression changes in myeloblastic leukemia
      cells stimulated with notch ligands.
AB  - BACKGROUND: Notch activation by ligand stimulation regulates the growth of acute
      myeloid leukemia (AML) cells. However, the molecular mechanisms underlying this
      have not been fully elucidated. MATERIALS AND METHODS: Two AML cell lines, THP-1
      and TMD7, and three Notch ligands, Jagged1, Dll1 and Dll4, were used. The effects
      of the ligands on cell growth, cleavage of Notch1, and the expression of various
      genes were examined by cell culture, immunoblotting, and quantitative RT-PCR,
      respectively. RESULTS: Ligand stimulation suppressed the growth of the THP-1
      cells but promoted that of the TMD7 cells. Immunoblots showed two cleaved Notch1
      bands, which became intense with different peak time from the start of
      stimulation. Ligand stimulation changed the expression levels of various genes
      related to cell proliferation. Some genes changed in opposite directions in the
      two cell lines. The three ligands had similar effects on gene expression.
      CONCLUSION: The time course for Notch1 cleavage following ligand stimulation and
      the effects of stimulation on gene expression are shown.

PMID- 19846938
TI  - 3-Dimensional microarray analysis of estrogen signal-related genes in breast
      cancer tissues.
AB  - BACKGROUND: Expression analysis of estrogen response genes (ERGs) may help to
      predict the effectiveness of endocrine therapies in breast cancer patients. We
      produced a custom-made, 3-dimensional microarray system (3DMS), using previously
      identified ERGs, and analyzed expression of ERGs on breast cancer tissues.
      MATERIALS AND METHODS: aRNA was synthesized from 27 breast cancer tumors. The
      aRNAs were applied to the infrastructure of a 3DMS with spotted cDNA probes to 36
      ERGs. Data were analyzed by cluster analysis. RESULTS: All 27 specimens were
      classified clearly into one of two clusters based on whether the ERGs were up or
      down regulated. These groups correlated with high expression of ER (P<0.05) and
      Her2 (P<0.05). In some cases, ERG expressions were low even though the tumor was
      ER positive. CONCLUSION: 3DMS may be useful for accurately predicting prognosis
      and whether endocrine therapies targeting the ER would be effective in an
      individual breast cancer patient.

PMID- 19846939
TI  - BCL-2, BAX and P53 expression profiles in endometrial carcinoma as studied by
      real-time PCR and immunohistochemistry.
AB  - BACKGROUND: Apoptotic genes regulate apoptosis by the action of their pro- and
      antiapoptotic products. Among the most important proteins are p53 and Bcl-x
      family proteins. PATIENTS AND METHODS: The differential expression of these
      apoptotic genes were analyzed in relation to clinicopathological criteria in
      women with endometrial carcinoma. Thirty-three fresh tissues and 191 paraffin
      embedded tissues were analyzed by real-time PCR for bcl-2/bax ratio and
      immunohistochemistry for p53, bcl-2 and bax proteins. RESULTS: Bcl-2/bax ratio
      tended to increase in grade 3 samples compared to grade 1 tumors. Mutated p53 was
      frequently observed in serous-papillary endometrial carcinomas (p=0.018). Low
      (<10%) and moderate (10-50%) expression of mutated p53 was observed in tumors
      with high expression of bax protein (>0.7). CONCLUSION: The Bcl-2/bax ratio is
      increased in grade 3 tumors. Bax protein shows a strong tendency for expression
      in the third group of clinical staging (stage IIb, III and IV). Poorly
      differentiated tumors highly expressed mutated p53.

PMID- 19846940
TI  - Evaluation of the cytotoxic and genotoxic effects of orthodontic bonding
      adhesives upon human gingival papillae through immunohistochemical expression of
      p53, p63 and p16.
AB  - BACKGROUND: Numerous in vitro studies have shown that composite materials,
      commonly used for restorations in conservative dentistry, and in orthodontics to
      anchor brackets to the tooth enamel, have cytotoxic and genotoxic effects. The
      study determined expression of p53, p63 and p16, biomarkers useful for predicting
      potential genotoxicity. PATIENTS AND METHODS: p53, p63 and p16 expression was
      determined immunohistochemically in the gingival papillae of 99 patients (69
      banded orthodontically for at least one year, brackets bonded to teeth with
      filled flowable composite resin, 30 without orthodontic banding as controls). The
      papillae samples were removed surgically and examined to evaluate morphological
      and biological alterations. RESULTS: In no case were morphological alterations
      visible by microscopy out of the 69 banded patients; four (5.80%) were positive
      for p53 and two for p63 expression in the basal and suprabasal layers (2.90%).
      One patient was positive for p16 (1.45%). No control case was positive for any of
      the biomarkers (0.00%). CONCLUSION: The significance of p53, p63 and p16
      positivity, and whether these proteins may serve as biomarkers to predict the
      risk of developing oral lesions (dysplasia, oral cancer) is still unclear.
      Although details of the mechanisms leading to cell death, genotoxicity and cell
      cycle delay are not fully understood, resin monomers may alter cell function in
      the oral cavity.

PMID- 19846941
TI  - Evaluation of cucurbitane-type triterpenoids from Momordica balsamina on P
      glycoprotein (ABCB1) by flow cytometry and real-time fluorometry.
AB  - BACKGROUND: Cancer cells become refractory to chemotherapy as a consequence of
      their overexpressing ABC transporters that extrude not only the therapeutic agent
      but other unrelated compounds such as chemotoxins and biocides before they can
      reach their intended targets. A compound that can inhibit the activity of these
      transporters may find use as an adjunct to chemotherapy that had been rendered
      ineffective. MATERIALS AND METHODS: Four curcubitane-type triterpenes isolated
      from Momordica balsamina Linn. (Cucurbitaceae), a plant from Mozambique were
      evaluated for their inhibition of the ABC transporter P-glycoprotein coded by the
      human ABCB1 gene transfected into mouse lymphoma cells. The evaluation was
      conducted by flow cytometry using rhodamine 123 and real-time fluorometry
      assessing accumulation of ethidium bromide (EB) on a real-time basis. RESULTS:
      Among the compounds isolated, the most active was 7-methoxycucurbita-5,24-diene
      3beta,23(R)-diol, which inhibited the efflux of ethidium bromide (EB) and
      rhodamine 123 from the ABCB1-transfected mouse lymphoma cell. CONCLUSION: Real
      time fluorometry replicated the flow cytometric results with significant
      advantages for the evaluation of efflux pump inhibitors. The substitution of side
      groups on the cucurbitane skeleton appears to be significant in the inhibition of
      ABCB1 activity.

PMID- 19846942
TI  - Doxycycline induces apoptosis in PANC-1 pancreatic cancer cells.
AB  - BACKGROUND: Tetracyclines such as doxycycline are reported to possess cytotoxic
      activity against mammalian tumor cells, but the mechanism of their effects on
      cell proliferation remains unclear. MATERIALS AND METHODS: The antitumor effect
      of doxycycline was investigated in human pancreatic cancer cell line, PANC-1. We
      also investigated the effect of doxycycline on expression of a potent
      proangiogenic factor, interleukin (IL)-8. RESULTS: In excess of 20 microg/ml,
      cytotoxic effects of doxycycline were accompanied by G(1)-S cell cycle arrest and
      DNA fragmentation in PANC-1 cells. Doxycycline consistently activated
      transcription of p53, p21 and Fas/FasL-cascade-related genes, while reducing the
      expression of Bcl-xL and Mcl-1. Doxycycline (5 microg/ml) below the cytotoxic
      level suppressed endogenous and paclitaxel-induced IL-8 expression. In the mouse
      xenograft model, doxycycline treatment was shown to suppress tumor growth by 80%.
      CONCLUSION: These data suggest that doxycycline exerts its antitumor effect by
      activating proapoptotic genes, inhibiting IL-8 expression, and suppressing
      antiapoptotic genes.

PMID- 19846943
TI  - Molecular imaging application of radioiodinated anti-EGFR human Fab to EGFR
      overexpressing tumor xenografts.
AB  - BACKGROUND: Suitable diagnostics could identify patients who might benefit from
      targeted therapies. Molecular imaging is a promising method estimating the
      expression of specific molecules in vivo, and the goal of this study was to
      evaluate a radioiodinated anti-epidermal growth factor receptor (EGFR) human Fab
      as a molecular imaging agent for diagnosis. MATERIALS AND METHODS: Three human
      tumor cell lines representing tumors with different levels of EGFR expression
      were selected and their corresponding xenografts produced. (125)I was conjugated
      to a human anti-EGFR Fab that recognizes the native extracellular domain of EGFR
      evidenced by immunoprecipitation (IP) and fluorescence-activated cell sorting
      (FACS) assays. Single-photon-emission computed tomography (SPECT) imaging of
      (125)I-Fab being administered to nude mice bearing xenografts were obtained, and
      further analyzed by region of interest (ROI) assay. RESULTS: The (125)I-Fab was
      achieved successfully without losing its immunoreactivity. The scintigrams as
      well as ROI assay showed that (125)I-Fab was able to clearly quantitatively
      distinguish the different expression levels of EGFR in vivo. CONCLUSION: (125)I
      Fab is a potential molecular imaging agent for clinical diagnosis of EGFR
      overexpressing tumors.

PMID- 19846944
TI  - MG-63 osteoblast-like cells enhance the osteoprotegerin expression of PC-3
      prostate cancer cells.
AB  - BACKGROUND: Osteoprotegerin (OPG) expression participates in the pathophysiology
      of osteoblastic metastasis in prostate cancer. MATERIALS AND METHODS: We
      investigated whether the expression of OPG of PC-3 prostate cancer cells grown in
      3-D collagen gels is stimulated by co-culture with MG-63 osteoblast-like cells.
      The expression of Runx2 (Cbfa1) and OPG were assessed by reverse transcription
      polymerase chain reaction and Western blot analysis. RESULTS: OPG and Runx2 were
      expressed in both PC-3 and MG-63 cells. OPG expression was remarkably enhanced in
      PC-3 cells grown in co-culture with MG-63 cells in a time-dependent manner. Runx2
      expression of PC-3 cells was not altered by their co-culture with MG-63 cells.
      OPG expression of PC-3 cells was altered neither by insulin-like growth factor I
      (IGF-1), transforming growth factor beta1 (TGFbeta1), interleukin 6 (IL-6) nor by
      dexamethasone and zoledronic acid exogenously added to PC-3 cells. CONCLUSION:
      The enhancement of the OPG expression in PC-3 cells by MG-63 cells is not
      mediated by IGF-1, IL-6 and TGFbeta1.

PMID- 19846945
TI  - HER2 status on persistent disseminated tumor cells after adjuvant therapy may
      differ from initial HER2 status on primary tumor.
AB  - BACKGROUND: Persistence of disseminated tumor cells (DTCs) is observed in 10 to
      15% of breast cancer patients and is associated with poor prognosis. These
      patients might benefit from secondary adjuvant targeted therapy. The aim of this
      study was to assess HER2 status of persistent DTCs to determine whether the use
      of HER2-targeted agents might be a therapeutic option in patients with tumor cell
      persistence. PATIENTS AND METHODS: Bone marrow was obtained from 85 primary
      breast cancer patients intraoperatively and after completion of systemic
      treatment (median follow-up of 13 months; range: 6-30 months). Immunofluorescence
      double staining was used for identification of cytokeratin-positive, HER2
      positive cells. RESULTS: A total of 31 out of 85 (36%) patients had DTCs
      preoperatively. Out of 85 (16%) patients, 14 were DTC positive after completion
      of surgery and adjuvant cytotoxic therapy. Five of these patients had HER2
      positive DTCs, however, the corresponding tumor was HER2 positive in only one
      case. The remaining nine patients with HER2-negative DTCs had HER2-negative
      primary tumors. CONCLUSION: HER2-positive DTCs can be detected in patients with
      HER2-negative tumors, even after adjuvant therapy. Such patients may benefit from
      (secondary) HER2-targeted therapy in an adjuvant setting.

PMID- 19846947
TI  - Expression of L1 cell adhesion molecule is a significant prognostic factor in pT3
      stage gastric cancer.
AB  - BACKGROUND: L1, a 200-220 kDa transmembrane glycoprotein of the immunoglobulin
      superfamily, has been shown to affect prognosis of various types of cancer and
      was shown to enhance peritoneal metastasis in ovarian cancer in vivo. PATIENTS
      AND METHODS: Immunostaining with anti-L1 antibody was performed with 72
      surgically resected pT3-stage gastric cancer specimens. Correlation of
      immunoreactivity with clinicopathological variables was evaluated and survival
      curves were compared between L1-positive and negative cases. RESULTS: L1 was
      detected in 15 specimens (21%), more often among the intestinal-type cancer. No
      correlation was observed between L1 expression and presence of free cancer cells
      in the peritoneal cavity or development of peritoneal carcinomatosis during the
      follow-up. Nevertheless, prognosis of patients with L1-positive cancer was
      significantly inferior (p=0.024), particularly among the diffuse-type cancer
      cases. CONCLUSION: L1 was associated with poor outcome in gastric carcinoma.
      However, its association with the formation of peritoneal metastases or the
      presence of free cancer cells in the abdominal cavity was not observed. Further
      study to identify the role of L1 in gastric cancer progression and metastasis is
      warranted.

PMID- 19846946
TI  - Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by
      combinations of the phytochemicals EGCG, genistein and quercetin.
AB  - Prostate cancer (CaP) is a significant cause of death in American men. While men
      residing in Asia show a lower incidence of hormone-refractory prostate cancer
      (HRPC) compared to Caucasian males, Asian men who move to and live in the United
      States and adopt a western lifestyle have HRPC rates indistinguishable from
      Caucasian males. These findings suggest that Asian diets contain ingredients that
      might protect against the development of HRPC. The identity and mechanisms of
      such HRPC protective agents remain to be elucidated. An Asian diet may confer
      protection against HRPC owing to functional synergy between bioactive dietary
      agents, thus broadening the chemopreventive index, with increased distinct
      anticancer properties and decreased untoward effects. Here, whether or not a
      combination of epigallocatechin gallate (EGCG), genistein and quercetin,
      phytochemicals present in a traditional Asian diet, might exert synergy in
      controlling proliferation and gene expression was investigated in CWR22Rv1 CaP
      cells, an in vitro model mimicking CaP transition from AD (androgen dependence)
      to HRPC. Cell proliferation was inhibited approximately 40%, approximately 15%
      and approximately 20%, respectively by 2.5 microM EGCG, genistein and quercetin
      used alone. The co-administration of 2.5 microM of these phytochemicals
      suppressed proliferation synergistically in the CWR22Rv1 cells maintained in RPMI
      1640 supplemented with 10% fetal bovine serum, but not in the cells maintained as
      serum-free cultures. Synergy in the expression of androgen receptor, tumor
      suppressor p53 and detoxification enzyme quinone reductase type 1, denoted NQO1,
      was also observed for the combined phytochemicals. These results demonstrate the
      feasibility of developing a diet-based combinatorial approach for CaP prevention
      and treatment and raise the possibility that serum added to culture medium might
      affect uptake, bioavailability and biological efficacy of dietary phytochemicals.

PMID- 19846948
TI  - 192R allele of paraoxanase 1 (PON1) gene as a new marker for susceptibility to
      bladder cancer.
AB  - BACKGROUND: The human body has a number of endogenous free-radical scavenging
      systems. Paraoxonase1 (PON1) is one of the enzymes involved in such systems. The
      purpose of this study was to investigate the relationship between bladder cancer
      and the polymorphism of PON1 which results in Q/R substitution at codon 192. This
      is the first report of this polymorphism in bladder cancer. PATIENTS AND METHODS:
      Seventy-six bladder cancer patients and 135 healthy controls took part in the
      study. DNA from paraffin-embedded tissues for patients and from blood cells for
      controls was extracted. The distribution of PON1(192) polymorphism was determined
      by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism
      (RFLP) techniques. RESULTS: There was significant difference in PON1 genotype
      frequencies (patients/controls QQ: 8/37, QR: 53/84, RR: 15/14, p=0.007) between
      the control and bladder cancer patients. Moreover, in patients there was
      significant association of the RR genotype of PON1 with invasive growth pattern
      (p=0.027), perineural invasion (p=0.016), distant metastasis (p<0.001), radical
      cystectomy (p=0.016) and death (p=0.005). CONCLUSION: In patients, the QQ
      genotype was statistically less frequent, while the RR genotype frequency was
      somewhat less than in controls. QQ type PON1 enzyme activity might be protective
      for bladder carcinogenesis. These findings support that genotypical differences
      of PON1 might contribute to prognosis and pathogenesis of bladder cancer.
      Arylamines are well-known bladder carcinogens, especially after a sulfate or an
      acetate esterification and PON1 has arylesterase activity. We hypothesize that
      arylesterase activity of PON1 would help the formation of free-radical type
      arylamine derivates on the bladder epithelial surface, so that secondary
      metabolites of paraoxon or related chemicals and biotransformed intermediates of
      arylamines might be involved in formation of bladder carcinoma.

PMID- 19846949
TI  - Mutations of LKB1 gene in pancreatic ductal adenocarcinomas induced by N
      nitrosobis(2-oxopropyl)amine in hamsters.
AB  - To evaluate an involvement of LKB1 gene alteration during pancreatic
      carcinogenesis, mutations in the LKB1 gene in hamster pancreatic duct
      adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) were
      investigated. Female Syrian golden hamsters received 30 mg/kg of BOP followed by
      repeated exposure to an augmentation pressure regimen consisting of a choline
      deficient diet combined with DL-ethionine then L-methionine and a further
      administration of 20 mg/kg BOP. A total of 10 PDAs obtained 10 weeks after
      beginning the experiment were examined for mutations using reverse transcription
      (RT)-polymerase chain reaction (PCR)-single-strand conformation polymorphism
      (SSCP) analysis. Mutations were detected in 3 out of the 10 PDAs (30.0%).
      Sequence analysis revealed the identity of these mutations to be a CCC to CCT
      (Pro to Pro) transition at codon 221, a CCG to CAG (Pro to Gln) transversion at
      codon 324 and a GAC to GGC (Asp to Gly) transition at codon 343. The LKB1 gene
      may be involved in the development of PDAs induced by BOP in hamsters.

PMID- 19846950
TI  - In vivo model of pseudomyxoma peritonei for novel candidate drug discovery.
AB  - Pseudomyxoma peritonei (PMP) is a clinical condition characterized by diffuse
      intraabdominal spread of mucinous tumor implants that form on peritoneal
      surfaces. To complement the efficacy of cytoreductive surgery, an effective
      cytotoxic drug is required as an intraperitoneal agent for microscopic
      cytoreduction locoregionally. To develop a model for drug discovery, human
      pseudomyxoma peritonei tumor implants consisting of a mixture of mucin and
      epithelial cells were injected into the peritoneal cavity of CBH/rnu/rnu rats. A
      fixed quantity of tumor (2 ml) was implanted in each of the 9 male rats. Over 90
      days, all rats developed PMP indicating that this in vivo animal model may become
      useful platform in a drug discovery program to allow drug efficacy testing
      against human PMP.

PMID- 19846951
TI  - Expression and mutational status of PDGFR in thymic tumours.
AB  - BACKGROUND: There is an ongoing search for new therapeutic targets in invasive
      non-resectable thymic tumours because of the low response rates in current
      chemotherapeutic treatment modalities. In this study, the possibility that
      platelet-derived growth factor receptor A (PDGFRA) and/ or PDGFRB may represent
      potential therapeutic targets in epithelial tumours of the thymus was
      investigated. PATIENTS AND METHODS: Tissue samples were obtained by thymectomy
      from 36 different patients with epithelial tumours of the thymus (26 thymomas
      types A, AB, B1-3 and 10 thymic carcinomas). Normal thymi from three young
      children were used as controls. The PDGFRA and PDGFRB protein expressions as well
      as the mutational statuses of exons 12, 14 and 18 of the PDGFRA gene were
      analyzed. RESULTS: All the subtypes of thymomas and the thymic carcinomas showed
      staining for PDGFRA, but no mutations in the known mutational hotspots were
      identified. Only about one third of the tumours stained for PDGFRB. PDGFRA and
      PDGFRB protein staining were slightly positively correlated. CONCLUSION: PDGFRA
      may represent a potential therapeutic target in thymic tumours.

PMID- 19846952
TI  - Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3,
      apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous
      carcinoma cancer cells.
AB  - Many phytochemicals have been recognized to have potential chemopreventive or
      chemotherapeutic efficacy in cancer treatment. In this study, we hypothesized
      that berberine would have anticancer activities in SCC-4 human tongue cancer
      cells. Results indicated that berberine reduced the viability of SCC-4 cells,
      which was initiated by the generation of reactive oxygen species, via an increase
      in cytosolic Ca(2+). Berberine-induced apoptosis was associated with a reduction
      of the mitochondrial membrane potential associated with changes in the Bax/Bcl-2
      ratio, release of cytochrome c from mitochondria and activation of down stream
      caspase-3. Real-time PCR showed that berberine stimulated gene expression of
      caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G. The present
      study demonstrated that berberine-mediated apoptosis of SCC-4 cells is regulated
      by ROS, mitochondria, caspase-3-dependent and mitochondria-dependent pathways,
      suggesting that berberine may be considered for future studies as a promising
      therapeutic candidate for human tongue cancer.

PMID- 19846953
TI  - Rapid induction of P-glycoprotein mRNA and protein expression by cytarabine in HL
      60 cells.
AB  - BACKGROUND: Overexpression of P-glycoprotein (P-gp), breast cancer resistance
      protein (BCRP) and glutathione-S-transferase pi (GSTpi) is associated with drug
      resistance in acute myeloid leukemia (AML). The short-term effects of drug
      exposure on their expression levels were investigated. MATERIALS AND METHODS: HL
      60 cells and drug-resistant sublines were cultured with or without daunorubicin
      (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P
      gp, BCRP and GSTpi were determined. RESULTS: After exposure to Ara-C, P-gp mRNA
      rapidly increased in all the cell lines. P-gp protein was detected in the
      sensitive cells after 8 h exposure to Ara-C. GSTpi mRNA increased in the
      resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR
      revealed rapidly increased P-gp and GSTpi mRNA in the resistant cells.
      CONCLUSION: Ara-C rapidly increases P-gp mRNA and protein expression in sensitive
      and resistant cells, and GSTpi mRNA in resistant cells, in vitro. This may be of
      clinical importance during AML induction chemotherapy.

PMID- 19846954
TI  - Estimation of relationship between descriptors and cytotoxicity of newly
      synthesized 1,2,3,4-tetrahydroisoquinoline derivatives.
AB  - We recently demonstrated that the cytotoxicity of nineteen 1,2,3,4
      tetrahydroisoquinoline derivatives depends on the molecular size (surface area,
      volume, width measured at 3-dimensional configuration), but not on most of the
      other electronic factors (Ishihara et al., Anticancer Res 29: 2265-2272, 2009).
      However, the information regarding cytotoxicity and molecular size in these
      compounds is limited. Here, a quantitative structure-activity relationship (QSAR)
      analysis using nineteen newly synthesized 1,2,3,4-tetrahydroisoquinoline
      derivatives was carried out. A semiempirical molecular-orbital method (CAChe 4.9,
      PM5) was applied to delineate the relationship between the cytotoxicity
      (evaluated by 50% cytotoxic concentration, CC(50)) of the nineteen derivatives
      (TD1-19) against human promyelocytic leukemia HL-60 and human oral squamous cell
      carcinoma (HSC-2, HSC-3, HSC-4) cell lines and sixteen chemical descriptors
      determined by CONFLEX/PM5 method or the molecular weight. There was some
      correlation between the CC(50) and the dipole moment for HSC-4 cells
      (r(2)=0.273), between the CC and log P for HL-60 and HSC-3 cells (r(2) 50 =0.191
      0.212), and between the CC(50) and distance of C-R(2) (at three dimensional
      configuration) (r(2)=0.394) and molecular weight (r(2)=0.292) for HL-60 cells. On
      the other hand, there was little or no correlation between the CC(50) and other
      descriptors. The present study demonstrated the dependency of the cytotoxicity of
      1,2,3,4-tetrahydroisoquinoline derivatives on hydrophobicity and distance between
      C-R(2) in the 3-dimensional configuration. These descriptors obtained from the
      CONFLEX/PM5 method may be utilized as a tool to analyze the biological effect of
      1,2,3,4-tetrahydroisoquinolines.

PMID- 19846955
TI  - Phase I/II study of PHY906/capecitabine in advanced hepatocellular carcinoma.
AB  - PHY906 is a Chinese medicine formula with claims for the treatment of severe
      gastrointestinal distress. PHY906 enhanced the therapeutic index of various
      chemotherapeutic agents in human hepatocellular carcinoma xenografts.
      Accordingly, here a phase I/II clinical study was conducted with the combination
      of capecitabine in patients with advanced, unresectable hepatocellular carcinoma.
      More than 60% of patients had either stable disease or better after two treatment
      cycles. Median overall survival was 9.2 months. Asian patients had a higher
      median overall survival (16.5 months) than non-Asian patients (6.2 months,
      p=0.03). Patients' quality of life did not deteriorate significantly during
      treatment. This finding supported further investigation of PHY906 as an adjuvant
      therapy of capecitabine in a larger hepatocellular cancer population.

PMID- 19846956
TI  - Reconstruction using a frozen bone method for osteosarcoma of the talus. A case
      report and review of the literature.
AB  - A case of osteosarcoma of the talus is reported. Osteosarcoma of the talus is
      very rare. The patient is alive and she has been continuously disease free for
      five years after surgery. This is the first case of osteosarcoma of the talus
      with reconstruction using a frozen bone method, an autograft containing tumor
      treated with liquid nitrogen. This is a rare case report of osteosarcoma of the
      talus without extrainvasion of the talus.

PMID- 19846957
TI  - Clinicopathological significance of Sip1-associated epithelial mesenchymal
      transition in non-small cell lung cancer progression.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) is a key event in cancer
      progression. The expression of EMT-related factors in non-small cell lung cancer
      (NSCLC) and their impact on clinicopathological variables was examined. PATIENTS
      AND METHODS: A total of 137 NSCLC patients who underwent surgical resections were
      investigated. The expression of Twist, Snail, smad-interacting protein 1 (Sip1),
      E-cadherin, N-cadherin, vimentin and beta-catenin was detected by
      immunohistochemical analyses. RESULTS: The expression of Sip1 was associated with
      the reduced expression of E-cadherin (p=0.04) and the positive expression of N
      cadherin (p=0.04). There was no association between the expression of Twist nor
      Snail and the epithelial or mesenchymal markers. The expression of Sip1
      correlated with advanced T status (p=0.01), tumor diameter (p=0.01) and advanced
      stage (p=0.01). Furthermore, the expression of Sip1 was associated with poor
      postoperative overall survival (p=0.02). CONCLUSION: The expression of Sip1 is
      significantly associated with tumor growth and poor prognoses in NSCLC and EMT
      might be activated via Sip1 expression and result in accelerated tumor growth and
      poor survival in NSCLC.

PMID- 19846958
TI  - Cancer nanotargeted radiopharmaceuticals for tumor imaging and therapy.
AB  - Cancer is the second leading cause of death in the world. Radiolabeled
      nanocarriers or nanoparticles can be designed and used for cancer diagnostic and
      therapeutic purposes when tagged with appropriate radionuclides. Current progress
      in nanotechnology and nanomedicine has exploited the possibility of designing
      tumor-targeted nanocarriers able to deliver radionuclide payloads in a selective
      manner to improve the efficacy and safety of cancer imaging and therapy. The
      major nanocarriers include liposomes, dendrimers, quantum dots, iron oxide and
      carbon nanotubes. In addition, the combining of tumor specific multifunctional
      and multimodality nanocarriers will hopefully achieve earlier tumor detection and
      better tumor treatment. Several radiolabeled multifunctional and multimodality
      nanoparticles have been effectively demonstrated in detecting and treating cancer
      in animal models. However, further preclinical and clinical efficacy and toxicity
      studies are required to translate these advanced technologies to the health care
      of cancer patients. The aim of this article is to provide a brief overview of
      current status of applications, advantages and up-to-date research and
      development of nanotargeted radiopharmaceuticals in cancer imaging and therapy.

PMID- 19846959
TI  - Methylene blue dye, an accurate dye for sentinel lymph node identification in
      early breast cancer.
AB  - PURPOSE: The aim of this prospective study was to analyze the safety of methylene
      blue dye (MBD) and compare its efficacy with that of isotopic mapping for
      sentinel lymph node (SLN) identification in breast cancer. PATIENTS AND METHODS:
      The SLN procedure, involving isotopic mapping and MBD (subareolar
      intraparenchymal injections of 2 mL, 10 mg/mL), was performed on 100 patients
      with early breast cancer. RESULTS: The procedure was safe with a success rate of
      99%; SLNs were, respectively, found in 65% by MBD, in 73% by lymphoscintigraphy
      and in 94% by gamma-probe. Out of 40 metastatic SLNs, 37 were "hot" and 32
      stained. Digital examination allowed the detection of 2 additional metastatic
      LNs. CONCLUSION: MBD is safe and combination mapping associated with digital
      examination is the superior method. Modification of the procedure, favouring
      injections of dilute MBD (4 mL, 1.25 mg/mL) increases MBD efficiency (90%) and
      maintains low rates of complications.

PMID- 19846960
TI  - High-dose octreotide acetate for management of gastroenteropancreatic
      neuroendocrine tumors.
AB  - BACKGROUND: Long-acting sandostatin (S-LAR; octreotide acetate) is well tolerated
      and effective for symptom control and possibly disease control in
      gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We undertook a
      retrospective analysis to study the efficacy and tolerability of higher doses
      (more than 20-30 mg/month) of S-LAR in GEP-NETs. PATIENTS AND METHODS: With IRB
      approval, charts of all patients with GEP-NET who received S-LAR between June
      2002 to September 2007 at Roswell Park Cancer Institute were reviewed and their
      data analyzed. RESULTS: Fifty-four patients with GEP-NET received S-LAR; thirty
      required dose escalation. Patients received a median of 5 doses of S-LAR at
      conventional dose followed by up-titration of the dose for symptom control (20)
      and radiological progression (17). Median high dose of S-LAR was 40 mg (range: 40
      90 mg) with a median of 8.5 high doses received. No treatment related toxicities
      were seen. The estimated 1-year survival for patients on conventional dose alone
      was 0.77 (95% CI of 0.50 to 0.91) and those on high-dose was 0.88 (95% CI of 0.68
      to 0.96) (p=0.4777) while median time to any other intervention was 2.9 months
      versus 17.7 months (p=0.12). CONCLUSION: Dose escalation of S-LAR is well
      tolerated and may provide longer disease control.

PMID- 19846961
TI  - Determinants of homocysteine levels in colorectal and breast cancer patients.
AB  - BACKGROUND: Homocysteinemia has been associated with oncogenic risk. This study
      was designed to investigate the homocysteine (Hcy) genotype/phenotype
      interactions together with the inflammatory and nutritional status of cancer
      patients. PATIENTS AND METHODS: The Hcy levels were analyzed in 47 cancer
      patients in association with methylenetetrahydrofolate reductase (MTHFR)
      polymorphisms, folate and inflammatory markers. RESULTS: The MTHFR C677T and
      A1298C genotype distributions did not differ from those predicted by the Hardy
      Weinberg distribution. Conversely, the Hcy levels were higher in the cancer
      patients (p=0.04), who were also characterized by low-grade inflammation. The Hcy
      levels correlated with the interleukin-6 (IL-6) (p=0.001), tumor necrosis factor
      alpha (TNF-alpha) (p=0.042) and folate (p<0.0001) levels of the patients.
      Multivariate analysis showed that TNF-alpha (p=0.014) and folate (p=0.019) were
      independent predictors of elevated Hcy levels in the cancer patients. CONCLUSION:
      The MTHFR polymorphisms do not significantly contribute to tHcy (total Hcy)
      levels in cancer patients, and cancer-related inflammation may be associated with
      elevated tHcy levels, possibly involving a TNF-alpha mediated pathway.

PMID- 19846962
TI  - Hepatic arterial infusion for unresectable colorectal liver metastases combined
      or not with systemic chemotherapy.
AB  - BACKGROUND: The hypothesis was tested that systemic chemotherapy might contribute
      to improving overall survival (OS) of patients with unresectable colorectal liver
      metastases treated with hepatic arterial infusion (HAI). PATIENTS AND METHODS: We
      considered 153 consecutive patients retrospectively divided into group A (n=72)
      treated with HAI alone (floxuridine [FUDR] + leucovorin [LV]), and group B (n=81)
      treated with HAI combined with systemic chemotherapy (5-fluorouracil [5FU] + LV).
      RESULTS: No significant difference in OS was observed between the two groups.
      Median OS was better in patients with <50% of liver involvement (21.3 vs. 13.2
      months; p<0.0001) and in responders vs. non-responders (24.4 vs. 13.4 months;
      p<0.0001). The combination of low tumor load with good tumor response to HAI was
      the only variable retained on multivariate survival analysis, associated with a
      better clinical outcome (median OS: 34.2 months). CONCLUSION: Our study does not
      support the use of FUDR-based HAI combined or not with 5FU-based systemic
      chemotherapy as the first-line therapeutic approach to unresectable colorectal
      cancer liver metastases. The identification of responsive patients would improve
      the therapeutic index of this HAI regimen.

PMID- 19846963
TI  - "Glassy" cells in Barrett's mucosa.
AB  - BACKGROUND: In 1991 we detected glandular cells with "glassy" cytoplasm (GCs) in
      human gastric mucosa having intestinal metaplasia (IM). GCs were subsequently
      found in the gastric mucosa of baboons. MATERIALS AND METHODS: The frequency of
      GCs (defined as glandular cells with a homogeneously pale, eosinophilic cytoplasm
      having a ground-glass appearance) was assessed in 403 human esophageal biopsies
      with columnar-lined esophagus. GCs may be in one gland or in a group of glands in
      metaplastic mucosa. RESULTS: Out of the 403 esophageal biopsies, 176 had cardiac
      glands with or without oxyntic cells (glandular metaplasia type 1 and 2,
      respectively) and the remaining 227 cases additionally had goblet cells (that is
      IM), glandular metaplasia type 3 (namely, Barrett's mucosa). Four out of the 403
      cases (0.99%) had glands with GCs; all four cases were recorded among the 227
      cases having glandular metaplasia type 3. Thus, GCs were detected in 1.8% of the
      cases with Barrett's mucosa. CONCLUSION: Previous studies showed that GCs were
      present in the gastric mucosa of specimens harbouring a gastric carcinoma. The
      present study showed that GCs are also present in Barrett's mucosa, a lesion
      often preceding epithelial dysplasia and carcinoma. The association between GCs
      and Barrett's mucosa deserves further investigation.

PMID- 19846964
TI  - Conservative management of low-grade endometrial stromal sarcoma followed by
      pregnancy and severe recurrence.
AB  - BACKGROUND: Since low-grade endometrial stromal sarcoma (LGESS) has the most
      favourable prognosis in comparison to other sarcomas, fertility-sparing surgery
      in young women has been reported in rare cases. However, such tumours almost
      always show positive sex steroid receptors and their evolution in the hormonal
      milieu of pregnancy remains unpredictable. CASE REPORT: We report the case of a
      34-year-old woman treated conservatively for LGESS who conceived rapidly after
      hysteroscopic resection of the tumour. In the post partum period, pelvic pain
      motivated a laparoscopic exploration which revealed severe peritoneal recurrence.
      CONCLUSION: This case report highlights the possible dramatic evolution of LGESS
      after pregnancy and suggests that definitive surgery should not be postponed but
      performed as soon as the diagnosis of ESS has been made.

PMID- 19846965
TI  - Relationships of P53 and Bak with EPO and EPOR in human colorectal cancer.
AB  - BACKGROUND: EPO (erythropoietin) counteracts p53-dependent apoptosis. EPO, which
      acts via its receptor EPOR, protects cells and inhibits apoptosis in normal cells
      and some cancer tissues by severe down-regulation of Bak. We aimed to investigate
      the relationship between p53 and Bak expression and EPO and EPOR in human
      colorectal carcinomas. MATERIALS AND METHODS: The expression of p53 was compared
      with Bak, EPO and EPOR in 96 colorectal carcinomas by means of
      immunohistochemistry. RESULTS: Purely nuclear p53 was significantly higher
      expressed in the moderately differentiated cancers in comparison with the poorly
      differentiated ones (p=0.007). P53 expression did not correlate with cytoplasmic
      markers: Bak, EPO and EPOR, but EPO and EPOR were significantly associated with
      Bak expression (p<0.001, r=0.524 and p<0.001, r=0.455, respectively). p53
      expression was not associated with disease-free survival during the 3 years and 9
      months long follow-up. CONCLUSION: A complete disruption of association between
      p53 and Bak could impair of p53-dependent apoptotic pathway that involves Bak.
      The relationship of Bak with EPO and EPOR is evidence of their co-expression
      suggesting competition between EPO mediated cell survival and Bak associated
      apoptosis in colorectal carcinomas.

PMID- 19846966
TI  - S100A8 and S100A9 expression is a crucial factor for dedifferentiation in thyroid
      carcinoma.
AB  - BACKGROUND: S100A8 plays a role in various functions of myeloid cells by forming
      a heterocomplex with S100A9. S100A8 and S100A9 are also known to be overexpressed
      in certain species of carcinomas. MATERIALS AND METHODS: In this study, the
      protein expression of S100A8 as well as that of S100A9 was investigated in
      thyroid tumors. RESULTS: All of the undifferentiated carcinomas were
      immunopositive for S100A8 and S100A9 and overlap between staining patterns of
      both proteins was observed. In poorly differentiated carcinomas, all the cases
      were negative for S100A8, while slight immunopositivity of S100A9 was seen in 2
      cases. Papillary carcinoma, follicular carcinoma, follicular adenoma and
      medullary carcinoma and normal follicules were negative for both proteins.
      CONCLUSION: S100A8 plays an important role in dedifferentiation of thyroid
      carcinoma possibly by forming a complex with S100A9.

PMID- 19846967
TI  - Survivin expression as a strong indicator of recurrence in urothelial bladder
      cancer. Predictive value of nuclear versus cytoplasmic staining.
AB  - BACKGROUND: Since its discovery in 1997, survivin has garnered significant
      interest due to its putative role as an inhibitor of apoptosis. Few studies have
      investigated the immunohistochemical status of survivin in urothelial bladder
      carcinoma. The subcellular localization of survivin (nuclear, cytoplasmic) and
      its differential predictive value is a parameter that previous studies have
      almost ignored. The aim of this study was to investigate the expression pattern
      of survivin in order to determine its potential prognostic significance.
      MATERIALS AND METHODS: Archival tumor tissue from 80 patients with urothelial
      carcinoma were analysed by immunohistochemistry. RESULTS: Nuclear and cytoplasmic
      positive scores of 61.25% (49/80) and 22.5% (18/80), respectively were found.
      Nuclear positive staining correlated strongly with increased grade (p=0.001),
      stage (p=0.039) and the probability of tumor recurrence (p=0.029). No
      relationship was found between the cytoplasmic survivin level and the
      clinicopathological parameters. Nuclear expression was identified as a
      significant independent predictor of relapse-free survival (p=0.016). CONCLUSION:
      Nuclear expression of survivin reflects an adverse disease outcome.

PMID- 19846968
TI  - Association between XRCC1 polymorphisms and head and neck cancer in a Hungarian
      population.
AB  - BACKGROUND: Head and neck cancer is a significant current health problem in
      Hungary because the mortality of this cancer has increased by 387% in the last
      thirty-two years. Because of the important role of the XRCC1 gene in DNA repair,
      we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of
      XRCC1 on the clinical outcome of head and neck cancer. PATIENTS AND METHODS: A
      polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP)
      method was used. A total of 108 samples were taken from intraoperatively removed
      formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched
      cancer-free control group was used to compare the frequency of polymorph
      variants. RESULTS: No significant difference was found between patients and
      controls in repect of the investigated polymorphisms. A significant difference
      was found between the patients with different XRCC1 194 polymorph status in
      clinical stage SIII. The survival proportion of patients with the Arg194Arg
      genotype was significantly lower than of those with the Arg194Trp genotype.
      CONCLUSION: The complex analysis of these factors may provide the basis for
      personal risk assessment and an opportunity for individualised therapy.

PMID- 19846969
TI  - Diverse prognostic roles of Akt isoforms, PTEN and PI3K in tumor epithelial cells
      and stromal compartment in non-small cell lung cancer.
AB  - AIM: By tissue microarray methodology, the expression of altered Akt isoforms,
      PTEN and PI3K and their prognostic significance in 335 non-small cell lung cancer
      (NSCLC) tumors were investigated. PATIENTS AND METHODS: Tumor tissue was sampled
      and immunohistochemically quantified in 335 tumors from stage I to IIIA NSCLC
      patients both from tumor epithelial cells and surrounding stromal tissue in
      resected specimens. Correlations were made with clinicopathological variables. In
      addition, the expression of these markers was compared to 20 lung tissue cores
      from patients without any history of malignancy. RESULTS: A significantly higher
      PTEN expression was observed in control tissue when compared with tumor
      (p=0.001). There was a significantly negative correlation between PI3K expression
      in control versus tumor tissue (p=0.001, r=-0.2). In univariate analyses, high
      tumor epithelial cell expression of non-phosphorylated Akt2 (p=0.014) was a
      positive prognostic indicator for disease-specific survival (DSS), while high
      tumor epithelial cell expression of p-Akt Thr(308) (p=0.045) was a negative
      prognosticator. High stromal expression of total Akt3 (p=0.0008) and total PI3K
      (p=0.0003) correlated with a good prognosis. In the multivariate analysis, tumor
      epithelial cell expression of p-Akt Thr(308) (p=0.0009) and Akt2 (p=0.004) and
      the stromal cell expression of Akt3 (p=0.0008) and PI3K (p=0.012) were
      independent prognostic factors for DSS. CONCLUSION: High expression of non
      phosphorylated Akt2 and low expression of p-Akt Thr(308) in tumor epithelial
      cells are independent predictors of improved survival in patients with primary
      NSCLC. In stromal cells, high expression of total Akt3 and total PI3K are both
      favourable independent prognostic indicators.

PMID- 19846970
TI  - Circulating tumor cells in metastatic breast cancer: timing of blood extraction
      for analysis.
AB  - PURPOSE: Circulating tumor cells (CTCs) can be detected in the peripheral blood
      of around 50% of patients with metastatic breast cancer. Their numbers are an
      independent predictor of the patient's progression-free survival (PFS) and of
      overall survival (OS). However, to date, none of the studies carried out with the
      most commonly used system of CTC determination (the CellSearch System, approved
      by the US Food and Drug Administration) has examined the intra-patient variation
      in CTC numbers, a variation that could impact on prognosis assessment.
      EXPERIMENTAL DESIGN: To evaluate possible circadian variations in the number of
      CTCs in patients with breast cancer a pilot study was conducted in which these
      cells were quantified 12 h apart (at 8:00 a.m. and 8:00 p.m. of the same day) in
      a cohort of hospitalized patients with metastatic breast cancer. RESULTS: Out of
      the 58 patients included in the study, 51 were evaluable. No statistically
      significant differences between day-time and night-time CTC numbers were observed
      (p=0.8427, Wilcoxon matched pair test). Only two of the patients were classified
      in different prognostic categories in the morning and night determinations (5 or
      more CTCs=poor prognosis group; <5 CTCs=good prognosis group). The prognostic
      classification of the remaining 49 patients was the same at 8:00 a.m. and 8:00
      p.m. CONCLUSION: The number of peripheral blood CTCs in metastatic breast cancer
      patients is not significantly different at 8:00 a.m. from that at 8:00 p.m. and,
      as such, indicates a lack of circadian rhythm with respect to CTC numbers in
      these patients.

PMID- 19846971
TI  - Single-institution outcome of high-dose interleukin-2 (HD IL-2) therapy for
      metastatic melanoma and analysis of favorable response in brain metastases.
AB  - BACKGROUND: High-dose interleukin-2 (HD IL-2) is known to produce durable
      responses in metastatic melanoma. The purpose of this study was to evaluate the
      response of metastatic melanoma to treatment with HD IL-2. PATIENTS AND METHODS:
      A retrospective analysis was performed on all adult patients with stage IV
      melanoma treated with HD IL-2 from January 2000 to October 2008 at the University
      of Minnesota. HD IL-2 was given intravenously every 8 hours at 600,000 IU/kg for
      a maximum of 14 doses per course. RESULTS: Fifteen patients with metastatic
      melanoma had been treated with HD IL-2. There were 4 patients exhibiting some
      response, with 1 complete response (CR), 1 partial response (PR), 1 mixed
      response (MR) and 2 stable disease (SD). Average time to disease progression
      (TTDP) was 5.67 months. Two patients had complete resolution of brain lesions
      after HD IL-2 therapy. One of these patients experienced CR and is disease free
      34 months after stopping therapy. The other patient experienced MR and is
      currently alive with disease, but without recurrence of brain lesions. Twelve out
      of the 15 patients received 2 courses of therapy. Common grade (G) 3 and 4
      adverse events included: hyperbilirubinemia (G 3=26.67%), hypotension (G 3=6.67%,
      G 4=6.67%), peripheral edema (G 3=26.67%), and pulmonary edema (G 3=13.33%).
      CONCLUSION: We propose further evaluation of HD IL-2 in patients with brain
      metastases because this patient population is typically considered ineligible for
      HD IL-2 therapy.

PMID- 19846972
TI  - Pegylated liposomal doxorubicin and carboplatin in late-relapsing ovarian cancer:
      a GINECO group phase II trial.
AB  - BACKGROUND: The GINECO group previously demonstrated that pegylated liposomal
      doxorubicin (PLD)-carboplatin combination was an effective and well-tolerated
      treatment for advanced ovarian cancer (AOC) patients in late relapse. The purpose
      of the present analysis was to confirm these results in a prospective cohort of
      late-relapsing AOC patients. PATIENTS AND METHODS: Eighty-one consecutive
      patients received PLD 30 mg/m(2), followed by carboplatin (area under the curve)
      5 mg min/ml, every 28 days for 6 courses or until progression. RESULTS: The
      objective response (OR) rate was 65.4%. The median progression-free survival
      (PFS) and overall survival (OS) were 13.6 months and 38.9 months, respectively.
      Haematological toxicities were more common than non-haematological toxicities.
      Non-hematologic adverse reactions were moderate and grade 3 palmar-plantar
      erythrodysesthesia was limited to one patient. No cardiotoxicity was observed and
      no toxic death occurred. CONCLUSION: These data support the clinical efficacy and
      tolerability of PLD in combination with carboplatin as second-line therapy for
      AOC patients in late relapse.

PMID- 19846973
TI  - Altered p53 and pRb expression is predictive of response to BCG treatment in T1G3
      bladder cancer.
AB  - BACKGROUND: The aim of this study was to determine the prognostic value of p53
      and retinoblastoma protein (pRb) expression in patients with stage T1 grade 3
      (T1G3) bladder cancer (BC) treated by transurethral resection of bladder tumour
      (TURBT) and intravesical instillations of bacillus Calmette-Guerin (BCG).
      MATERIALS AND METHODS: p53 and pRb expression were independently recorded within
      a homogeneous series of 27 patients. Fisher exact test and the log-rank test were
      carried out, along with Kaplan-Meier survival analysis. RESULTS: Sixteen tumours
      showed altered p53 expression, while 14 showed altered pRb expression. Overall, 7
      tumours showed normal expression of both markers, 10 altered expression of one of
      the two markers, and 10 altered expression of both markers. Only altered pRb
      expression was an independent predictor of both recurrence (p=0.037) and
      progression (p=0.018); altered expression of both markers was a strong predictor
      (p=0.001) of progression. CONCLUSION: This is the first study demonstrating that
      altered p53 and pRb expression are predictive of T1G3 BC response to BCG
      treatment. These findings provide grounds for inclusion and prospective
      validation of these markers in the decision-making process for treating BC.

PMID- 19846974
TI  - Clinical outcome of tailored adjuvant postoperative chemoradiotherapy in IB FIGO
      stage cervical cancer.
AB  - AIM: The aim of the present report is to review a mono-institutional experience
      of postoperative radiotherapy in selected patients with cervical cancer. PATIENTS
      AND METHODS: Between 1999 and 2008, fifty-one patients with high-risk stage IB
      cervical cancer underwent tailored adjuvant postoperative radiotherapy;
      concurrent chemoradiotherapy was administered to patients presenting a high risk
      of recurrence. The median follow-up was 58 months. RESULTS: All patients were in
      complete remission at first follow-up assessment. Ten patients were subject to
      recurrences between 7 and 54 months after treatment. The 2-year and 5-year
      disease-free survival rates were 88.1% and 74.9%, respectively; 2-year and 5-year
      overall survival rates of the whole group were 91.8% and 82.0%, respectively.
      Only one case of grade 4 and four cases of grade 3 side effects were reported.
      CONCLUSION: Tailored adjuvant postoperative chemoradiotherapy is able to obtain a
      satisfactory clinical outcome in patients with high-risk early-stage IB cervical
      cancer.

PMID- 19846975
TI  - Induction chemotherapy with docetaxel, 5-FU and CDDP (DFP) for advanced gastric
      cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility and efficacy of
      modified triplet chemotherapy with docetaxel, 5-fluorouracil and cisplatin as
      induction chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS:
      Treatment-naive patients with AGC were eligible. The regimen consisted of 350
      mg/m(2)/day 5-FU by continuous infusion on days 1 to 5, 10 mg/m(2)/day CDDP
      intravenously on days 1 to 5, and docetaxel at 60 mg/m(2)/day intravenously on
      day 1. After 2 cycles (each cycle consisted of 4 weeks), surgical resection was
      attempted, 2-4 weeks after the completion of the regimen. RESULTS: Eighteen
      patients were enrolled. Adverse events included grade 3 anorexia and nausea in
      16.7% and 11.1% and grade 4 leukocytopenia and neutropenia in 5.6% and 27.8%,
      respectively. The overall response rate was 44.4%. Surgery was conducted in 15
      patients. The 1- and 3-year survival rates were 75.6% and 51.1%, respectively.
      CONCLUSION: The modified triplet combination therapy is effective and well
      tolerated by patients with AGC.

PMID- 19846976
TI  - Treatment after the failure of gefitinib in patients with advanced or recurrent
      non-small cell lung cancer.
AB  - BACKGROUND: The optimal treatment for patients with progressive non-small cell
      lung cancer who initially show a good response to gefitinib is unclear. PATIENTS
      AND METHODS: This study retrospectively analyzed 60 consecutive patients who
      experienced treatment failure after achieving disease control with gefitinib and
      thereafter underwent post initial gefitinib treatment either with or without
      continuing gefitinib. RESULTS: Continuing gefitinib was independently associated
      with a good survival based on multivariate analyses (hazard ratio (HR)=0.51; 95%
      confidence interval (CI)=0.26-0.98; p=0.0426), and performance status at the
      failure of gefitinib (0.05; 0.02-0.17; p<0.0001). The adjusted HR of continuing
      gefitinib based on Cox regression analysis and a propensity score of 0.61 (95%
      CI, 0.41-0.92) indicated an association between a prolonged survival and the
      continuation of gefitinib. CONCLUSION: In addition to post gefitinib treatment,
      continuing the administration of gefitinib should be considered in patients who
      previously achieved disease control with gefitinib, even after a failure of
      gefitinib.

PMID- 19846977
TI  - A throbbing pain in the head: trastuzumab-induced migraine.
AB  - Trastuzumab, an epidermal growth factor receptor inhibitor, is used in the
      treatment of both early-stage and metastatic breast cancer. In general it is well
      tolerated, with a flu-like syndrome occurring frequently a few hours after
      administration, including symptoms such as fever, sweating, skin rash, nausea and
      headache. A migraineous headache however has never been described as an adverse
      event. Here we present a patient in whom a strong relationship between
      trastuzumab infusion and a migraineous headache syndrome was present, without
      evidence of metastatic disease. Treatment with corticosteroids for the infusion
      related complaints resulted in significant pain relief.

PMID- 19846978
TI  - Elevated malondialdehyde correlates with the extent of primary tumor and predicts
      poor prognosis of oropharyngeal cancer.
AB  - The aim of the study was to investigate the relationship between plasma levels of
      malondialdehyde (MDA), a routinely used marker of oxidative stress, and squamous
      cell carcinoma of the oral cavity and oropharynx (OSCC). The prospective cohort
      study comprised a total of 67 patients who underwent surgery for OSCC. MDA was
      assessed using high performance liquid chromatography. The MDA levels in the
      pooled T1-2 patients were lower than in the patients with T3-4 tumors. A negative
      correlation of MDA and tumor grade was shown. Seventeen patients who manifested
      recurrence during the 49.6 months follow-up had significantly increased MDA
      compared to those staying in complete remission. Kaplan-Meier analysis revealed
      that the median disease-free interval and overall survival in the group with MDA
      > median was 19.3 and 22.5 months respectively, in contrast to 31.5 and 31.6
      months respectively, in patients with MDA < or = median. The prognostic value and
      low cost of MDA measurement could make it a versatile and useful prognostic tool
      for the identification of OSCC patients with a high risk of recurrence.

PMID- 19846979
TI  - An open-label dose-escalation study of BIBF 1120 in patients with relapsed or
      refractory multiple myeloma.
AB  - BACKGROUND: To determine the maximum tolerated dose (MTD) and dose-limiting
      toxicities (DLTs) of BIBF 1120, a triple angiokinase inhibitor administered once
      daily in patients with advanced multiple myeloma. PATIENTS AND METHODS: This
      Phase I study included 17 patients. Planned dose escalations of BIBF 1120 were
      100, 200, 250 and 300 mg. Safety and pharmacokinetic (PK) assessments were
      performed. RESULTS: Two DLTs (200 and 250 mg) occurred due to increased gamma
      glutamyltransferase levels (CTC grade 3). The 250 mg dose was well tolerated; no
      dose escalation beyond 250 mg was made. The most common adverse events included
      diarrhoea, nausea and vomiting. No detectable deviation from dose linear PKs was
      observed. Regarding tumour control, two patients had stable disease for > or = 4
      months. CONCLUSION: BIBF 1120 was safe and well tolerated up to 250 mg/day. The
      MTD was not reached.

PMID- 19846980
TI  - Serum levels of CA15-3, KL-6 and BCA225 are positively correlated with each other
      in the general population.
AB  - BACKGROUND: Carbohydrate antigen 15-3 (CA15-3), Kerbs von den Lungen (KL-6) and
      breast cancer antigen 225 (BCA225) are widely used tumor markers for breast and
      lung cancer respectively. PATIENTS AND METHODS: We analyzed 460 Japanese
      volunteers for 99 items on blood examination including 27 serum tumor markers.
      Correlations between 27 tumor markers and the other items were statistically
      analyzed. RESULTS: Positive correlations were identified between CA15-3 vs. KL-6,
      CA15-3 vs. BCA225, and KL-6 vs. BCA225, with correlation coefficients of 0.84,
      0.86, and 0.79, respectively. CONCLUSION: This is the first report to show a
      positive correlation among these markers in the general population. All of these
      are recognized as belonging to the mucin family, and this might be the reason for
      the positive correlation.

PMID- 19846981
TI  - Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided versus
      empirical chemotherapy in unresectable non-small cell lung cancer.
AB  - BACKGROUND: We retrospectively compared adenosine triphosphate-based chemotherapy
      response assay (ATP-CRA)-guided and empirical chemotherapies for unresectable non
      small cell lung cancer (NSCLC) in this case-control study. PATIENTS AND METHODS:
      Unresectable NSCLC patients receiving ATP-CRA-guided platinum-based doublets as
      first-line therapy were enrolled as cases (n=27; 14 platinum-sensitive and 13
      platinum-resistant patients). Performance status, stage, and chemotherapeutic
      regimen-matched patients receiving empirical chemotherapy were selected from the
      retrospective database as controls (n=93) in a case to control ratio of
      approximately 1:3. RESULTS: Response rate and survival (progression-free;
      overall) in both groups were not significantly different. However, the platinum
      sensitive subgroup by ATP-CRA showed a higher response rate than the empirical
      group (71 versus 38%; p=0.023) with a trend toward longer progression-free
      survival (8.7 versus 4.8 months for platinum-sensitive versus empirical; p=0.223)
      and overall survival (not reached versus 12.6 months for platinum-sensitive
      versus empirical for p=0.134). CONCLUSION: ATP-CRA may be helpful in selecting
      platinum-responsive patients in unresectable NSCLC. We consider that nonplatinum
      doublets in platinum-resistant patients by ATP-CRA may be a more adapted approach
      than platinum-based doublets in future clinical trials.

PMID- 19846982
TI  - Comparison between 99mTc-sestamibi scintimammography and X-ray mammography in the
      characterization of clusters of microcalcifications: a prospective long-term
      study.
AB  - BACKGROUND: The early diagnosis of non-palpable breast cancer is the object of
      recent developments in the imaging procedures employed for screening purposes. In
      some patients, the presence of microcalcifications (MC) is the only indication of
      tumor. Although X-ray mammography (MRx) has high sensitivity in detecting MC, its
      specificity is however too low for diagnostic purposes. The aim of this study was
      to compare (99m)Tc-sestamibi scintimammography (SMM) and MRx in the differential
      diagnosis between benign and malignant clusters of MC and to assess the possible
      incremental value of SMM on specificity. PATIENTS AND METHODS: A total of 283
      consecutive women (mean age 53+/-8 years) with MC identified on X-ray mammograms
      underwent SMM. Scintigraphic images were acquired 10 minutes after the i.v.
      injection of (99m)Tc-sestamibi (740 MBq). Planar images of both breasts were
      simultaneously obtained in the lateral prone position and in the anterior and
      oblique projections using a dual head camera. Sixty-nine women underwent surgery,
      whereas the remaining 214 patients had completely negative follow-up for 5 years
      (a 5-year follow-up period is considered the "gold standard" for diagnosing
      benign lesions). RESULTS: Histology demonstrated 32/69 primary breast carcinomas
      (prevalence of disease: 11% of all the 283 patients) and 37/69 benign lesions.
      The receiver operating characteristic (ROC) statistical technique was employed to
      compare the diagnostic value of Mrx alone to that of combined MRx and SMM. The
      detected difference between the areas under the MRx ROC curve (area=0.72,
      standard error 0.052) and the MRX and SMM ROC curve (area=0.86, standard error
      0.039) was statistically significant (p<0.01). Moreover, the combination of MRx
      and SMM provided a significant improvement of the negative predictive value
      (NPV=98%) for MC with low-suspicion of malignancy at MRx. CONCLUSION: SMM can be
      considered as a complementary tool in the pre-operative work-up of patients with
      breast lesions. Furthermore, the high negative predictive value of this
      technique, makes it especially valuable in the perspective of reducing the number
      of negative breast biopsies or unnecessary surgical interventions.

PMID- 19846983
TI  - Hypofractionated stereotactic radiotherapy and radiosurgery for the treatment of
      patients with radioresistant brain metastases.
AB  - AIM: To evaluate the efficacy of different radiotherapy treatment modalities in
      radioresistant brain metastasis. PATIENTS AND METHODS: A retrospective analysis
      was conducted on 78 patients with brain metastases from melanoma, sarcoma, or
      renal cell carcinoma primary tumours who underwent radiosurgery (20 Gy) and/or
      hypofractionated stereotactic radiotherapy (6x4 Gy or 7x4 Gy) with or without
      whole-brain radiotherapy at our Center. RESULTS: The actuarial median survival
      times for melanoma, renal cell carcinoma and sarcoma were 23, 22 and 7 months
      respectively, with a significant correlation to recursive partitioning analysis
      class. DISCUSSION: Our results show that these treatments were effective both in
      symptom palliation and in improving survival, suggesting that although outcomes
      generally remained poor in this study population, it is possible and important to
      control intracranial brain metastases.

PMID- 19846984
TI  - RANTES promoter genotype and gastric cancer risk in a Japanese population.
AB  - BACKGROUND: A complex interaction of genetic and environmental factors is
      relevant in gastric carcinogenesis. Previous studies reported that the expression
      of RANTES is enhanced in Helicobacter pylori-infected gastric mucosa. Elevated
      serum level of RANTES in gastric cancer patients was also reported. We aimed to
      clarify the effect of RANTES promoter polymorphism on the risk of gastric cancer
      (GC) in a Japanese population. MATERIALS AND METHODS: A total of 191 GC and 335
      non-cancer patients including H. pylori-positive gastritis (n=180) and H. pylori-
      negative healthy stomach (n=155) were genotyped for polymorphisms at -28 C/G in
      the RANTES gene promoter region. RESULTS: RANTES promoter genotype distributions
      were not significantly different among GC, overall non-cancer patients, healthy
      stomach and gastritis. In the comparison of genotype frequency between GC and
      healthy stomach, only a weak correlation was found between -28G/G genotype and GC
      in individuals more than 70 years of age (odds ratio (OR)=7.65, 95% confidence
      interval (CI)=0.78-75.0, p=0.07), with advanced stage (OR=6.58, 95% CI=0.72
      59.77, p=0.07), lymph node metastasis (OR=7.20, 95% CI=0.79-65.46, p=0.06) and
      peritoneal dissemination (OR=10.93, 95% CI=0.96-124.64, p=0.07). CONCLUSION: The
      effect of -28 C/G polymorphism in the RANTES gene promoter on GC development may
      not to be very strong. The role of RANTES promoter polymorphism in gastric
      carcinogenesis needs further evaluation.

PMID- 19846985
TI  - The efficacy of endoscopic submucosal dissection compared with modified
      endoscopic aspiration mucosectomy by assessing the short-term therapeutic results
      for differentiated mucosal gastric cancer.
AB  - BACKGROUND: We developed a modified method of endoscopic aspiration mucosectomy
      (m-EAM) which includes the pre-cutting of the peripheral mucosa before
      aspiration, and which has been employed in this department since 1998. An
      endoscopic submucosal dissection (ESD), which enables the resection of a larger
      area of the lesion using newly-developed surgical devices, has also been employed
      here since March 2003. This study was performed to investigate the efficacy of
      ESD at the present time by assessing the short-term therapeutic results for the
      procedure in patients with a preoperative diagnosis of early-stage differentiated
      gastric mucosal cancer, by tumor diameter, as well as by comparing these results
      with those obtained previously with m-EAM. PATIENTS AND METHODS: The study
      included 110 patients with a preoperative diagnosis of early-stage differentiated
      gastric mucosal cancer (57 underwent m-EAM and 53 received ESD). A comparison was
      made between these two groups regarding the short-term therapeutic response (en
      bloc resection rate, curability, complications, and days of postoperative
      hospitalization) by the tumor diameter. RESULTS: The en bloc resection rate was
      significantly higher for patients with a tumor measuring 21 mm or larger who
      underwent ESD in comparison to that for those with a similar tumor size who
      underwent m-EAM (p<0.05). Complications were reported significantly more
      frequently in patients treated with ESD for a tumor measuring 11 mm or larger
      (p<0.05) in comparison those treated with m-EAM. There was no significant
      difference between the two groups with regard to the curability and the days of
      postoperative hospitalization. CONCLUSION: This study confirmed the efficacy of
      the ESD procedure which enables surgeons to perform a more reliable en bloc tumor
      resection.

PMID- 19846986
TI  - A phase II study of cisplatin and temozolomide in heavily pre-treated patients
      with temozolomide-refractory high-grade malignant glioma.
AB  - BACKGROUND: There is pre-clinical evidence of synergism between cisplatin and
      temozolomide due to higher inhibition of O(6)-alkyl-guanine-alkyltransferase
      (AGAT), an enzyme involved in the mismatch repair system and in the mechanisms of
      drug resistance to alkylating agents. PATIENTS AND METHODS: Heavily pre-treated
      patients with temozolomide-refractory high-grade malignant glioma received
      cisplatin at a dose of 75 mg/m(2) on day 1 and temozolomide at a dose of 150
      mg/m(2) on days 1 to 5 every 21 days until progression or major toxicity.
      RESULTS: Twenty-four patients were enrolled and a total of 96 cycles were
      delivered (median for each patient=4). Toxicity was manageable and mostly grade 1
      2: haematological, gastroenterological (nausea and vomiting) and fatigue. In
      patients with glioblastoma, an overall response rate of 29.4% was achieved, with
      no complete response, and with a disease control rate (responses plus
      stabilizations) of 64.7%. The median time to progression was 3.8 months (95%
      confidence interval 2.4-6.8), progression-free survival at 6 months was 28% and
      overall survival was 7.0 months (95% confidence interval 4.8-11.0). CONCLUSION:
      The combination of temozolomide and cisplatin is safe and moderately effective in
      the treatment of heavily pre-treated patients with relapsed high-grade glioma
      refractory to single-agent temozolomide.

PMID- 19846987
TI  - The follow-up of patients with non-muscle-invasive bladder cancer by urine
      cytology, abdominal ultrasound and urine CYFRA 21-1: a pilot study.
AB  - AIM: This study aimed to evaluate the accuracy of urine cytology, bladder
      ultrasound (US), urine cytokeratin 19 fragment assay (CYFRA 21-1) and the
      combination of these noninvasive modalities in the detection of recurrent bladder
      cancer. PATIENTS AND METHODS: In a total of 154 patients that were followed with
      cystoscopy after endoscopic resection of non-muscle-invasive bladder cancer, we
      performed and analyzed results of 311 observations that included cytology, CYFRA
      21-1, US. The urine concentration of CYFRA 21-1 was measured by an
      immunoradiometric assay. RESULTS: Cystoscopy and biopsy revealed recurrent
      bladder tumors in 21 patients. Most of the tumors (77%) were less than 10 mm in
      their largest diameter. Urine cytology, US and urine CYFRA 21-1 resulted in
      overall sensitivity of 19.1, 52.4 and 71.4% and specificity of 96.6, 99.7 and
      68.6%, respectively. Each of these methods used alone yielded false-negative
      results in patients harboring tumors at high risk of progression. The combination
      of all three methods had sensitivity and specificity of 90.5 and 67.2%,
      respectively. All three tests were negative in 197 of 311 observations (63.3%),
      missing only 2 low-risk tumors. CONCLUSION: The combined use of US, urinary CYFRA
      21-1 and cytology appears to be an effective, noninvasive approach for the
      detection of recurrent bladder tumors.

PMID- 19846988
TI  - Psychosocial outcomes in long-term survivors of high-grade osteosarcoma: a
      Japanese single-center experience.
AB  - AIM: The psychosocial outcomes in long-term survivors of osteosarcoma were
      investigated. PATIENTS AND METHODS: A questionnaire concerning the psychosocial
      status was completed by 30 long-term survivors of osteosarcoma. The family APGAR
      was employed for the evaluation of family function, social support questionnaire
      (SSQ) for social support, impact of event scale-revised (IES-R) for posttraumatic
      stress symptoms (PTSS), and posttraumatic growth inventory (PTGI) for
      posttraumatic growth (PTG). RESULTS: The family APGAR and SSQ scores were
      comparable to those of controls. The IES-R score was low, showing a low incidence
      of PTSS. The PTGI score was high, revealing marked PTG. On multiple regression
      analysis regarding the IES-R as a dependent variable, the family APGAR was
      associated with the IES-R. On multiple regression analysis regarding the PTGI as
      a dependent variable, the age at diagnosis, state of the affected limb and SSQ
      were associated with the PTGI. CONCLUSION: The incidence of PTSS was low, and PTG
      was marked in the long-term survivors of osteosarcoma. A high age at onset and
      amputation of the affected limb were associated with PTG. Support of the family
      function reduces PTSS, and the strengthening of social support facilitates PTG.

PMID- 19846989
TI  - Further studies on the frequency of colorectal cancer in Crohn's colitis: an 11
      year survey in the Northwest Stockholm County.
AB  - BACKGROUND: The frequency of colorectal carcinomas (CRC) evolving in patients
      with Crohn's colitis (CC) was assessed at the Danderyds University Hospital
      (DUH), one of two large hospitals in Northwest Stockholm County (NWSC). PATIENTS
      AND METHODS: A total of 121 patients with Crohn's disease (CD) were treated at
      this hospital between 1996 and 2006. All sections from colectomy specimens having
      CC and carcinoma were reviewed. RESULTS: Of the 121 patients with CD, 79.4%
      (96/121) had CC. Of the 96 patients with CC, 6.3% (n=6) developed a CRC between
      1996 and 2006. DISCUSSION: Recent studies at the other large hospital in NWSC
      showed that during the same period (1996-2006) 7.4% (n=21) of the 282 patients
      with CC, developed a CRC. During this 11-year period, 7.1% (n=27) of the 378
      patients with CC seen at the two hospitals that treat the vast majority of
      patients with CD in NWSC developed a CRC. By comparison, only 0.29% or 5,566
      patients (age-adjusted) out of the 1,900,000 inhabitants in the entire Stockholm
      County developed a CRC during the same period. These results, obtained at a
      comparative time-interval in the County, substantiate several recent meta
      analysis and population-based studies on the high cancer risk in patients with
      Crohn disease.

PMID- 19846990
TI  - Carboplatin-pemetrexed adjuvant chemotherapy in resected non-small cell lung
      cancer (NSCLC): a phase II study.
AB  - BACKGROUND: The aim of this study was to determine the progression-free survival
      (PFS) and toxicity associated with adjuvant administration of carboplatin and
      pemetrexed for completely resected patients with stage IB, II and IIIA non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-five eligible NSCLC
      patients received surgical resection for pathological stage IB, II or IIIA
      followed by postoperative adjuvant chemotherapy with carboplatin AUC5 and
      pemetrexed administered on days 1 and 14 on a 28-day cycle. Recombinant human
      granulocyte colony-stimulating factor (rhG-CF) was given prophylactically.
      RESULTS: The mean time to disease progression of patients was 26 months.
      Toxicities were generally mild to moderate and entirely manageable. CONCLUSION:
      The administration of carboplatin and pemetrexed is a safe, well-tolerated and
      convenient regimen in the adjuvant setting of completely resected NSCLC, with
      efficacy similar to that reported in other regimens but less toxicity.

PMID- 19846991
TI  - Prognostic value of serum tumor antigen CA19-9 after curative resection of
      colorectal cancer.
AB  - BACKGROUND: CA19-9 was evaluated as a prognostic marker for colorectal cancer and
      whether it could be helpful in addition to surveillance using CEA was also
      tested. MATERIALS AND METHODS: Serum CA19-9 levels were measured preoperatively
      in 1109 patients and monitored at 3-month intervals for the first 2 years
      postoperatively, and at 6-month intervals thereafter in 700 patients. RESULTS:
      Preoperative high CA19-9 was independent prognostic factor for recurrence. Among
      patients with recurrence, 21.4% had a high postoperative CA19-9. High
      postoperative CA 19-9 levels were more likely in patients with high preoperative
      levels. Postoperative CA19-9 increased more in patients with a peritoneal
      recurrence than in those with liver metastasis (p=0.002). Among patients with
      recurrence, CA19-9 increased in 7.8% of the patients with a normal follow-up CEA.
      CONCLUSION: Postoperative CA19-9 was more frequently elevated when peritoneal
      recurrence occurred. Data on CA19-9 levels provided 7.8% of additional
      information in predicting recurrence in this study.

PMID- 19846992
TI  - Retrospective study of venous thromboembolic and intracerebral hemorrhagic events
      in glioblastoma patients.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a common complication in glioblastoma
      (GB) patients. PATIENTS AND METHODS: A retrospective medical record review
      identified 294 GB patients with VTE or ICH; 146 patients with sufficient
      treatment records were included. Treatment approaches for GB patients who
      developed VTE were also reported. RESULTS: Of 146 patients, 41 (28%) developed
      VTE and 3 (2%) developed ICH. Seven (17%) of the 41 VTE patients developed
      recurrent VTE. Practice patterns for VTE treatment varied widely. Patient
      demographics were not significantly associated with VTE development. CONCLUSION:
      Despite a low incidence of ICH, even with anticoagulation therapy, physicians are
      reluctant to administer anticoagulants to GB patients with VTE. The optimum
      treatment for GB patients with VTE has not been established; however, the
      benefits of anticoagulation therapy may outweigh the risks of ICH. A prospective
      clinical trial to evaluate the potential benefits for deep venous thrombosis
      prophylaxis in GB patients is warranted.

PMID- 19846994
TI  - Should children with inherited metabolic disorders receive varicella vaccination?
AB  - The aim was to determine the rate of varicella infection and complications in
      children with disorders of intermediary metabolism (IEM) between the ages of 1
      and 16 years attending our national metabolic referral centre. Of 126 children
      identified, a response was received from 122. A history of previous varicella
      infection was identified in 64 cases (53%) and of varicella vaccination in 5
      (4%). Fifty-three (43%) patients apparently did not have a history of clinical
      varicella infection. Of the 64 children with a history of varicella infection,
      five required hospitalisation for complications, including life-threatening
      lactic acidosis in one patient with mitochondrial disease and metabolic
      decompensation in four patients. In conclusion, varicella infection may cause an
      increased risk of metabolic decompensation in patients with IEMs. We propose that
      a trial of varicella vaccination be considered for this cohort of patients with
      monitoring of its safety and efficacy.

PMID- 19846995
TI  - Child protection medical assessments: why do we do them?
AB  - INTRODUCTION: Child protection guidelines highlight the importance of medical
      assessments for children suspected of having been abused. AIM: To identify how
      medical assessments might contribute to a diagnosis of child abuse and to the
      immediate outcome for the child. METHOD: Review of all notes pertaining to
      medical assessments between January 2002 and March 2006. RESULTS: There were 4549
      child protection referrals during this period, of which 848 (19%) proceeded to a
      medical examination. 742 (88%) case notes were reviewed. Of the medical
      examinations, 383 (52%) were for alleged physical abuse, 267 (36%) for sexual
      abuse and 20 (3%) for neglect. 258 (67%) of the physical abuse cases were
      considered to have diagnostic or supportive findings as compared to 61 (23%) of
      the sexual abuse cases (chi2=146.31, p<0.001). In diagnostic or supportive
      examinations or where other potentially abusive concerns were identified, 366
      (73%) proceeded to further multi-agency investigation and 190 (41%) to case
      conference. 131 (69%) of these resulted in the registration of the child on the
      child protection register. Other health concerns were identified in 121 (31%) of
      physical and 168 (63%) of sexual abuse cases. CONCLUSION: In this case series,
      465 (63%) out of 742 examinations showed signs diagnostic or supportive of
      alleged abuse or highlighted other abusive concerns. This endorses the view that
      medical examination is an important component in the assessment of child abuse as
      it provides information to support or refute an allegation and helps to identify
      the health and welfare needs of vulnerable children.

PMID- 19846996
TI  - Editors should not be propagandists.

PMID- 19846997
TI  - Treatment for cryopyrin-associated periodic syndrome.

PMID- 19846998
TI  - Increase in childhood type 1 diabetes in Europe.

PMID- 19846999
TI  - Prolonged breast feeding reduces later cardiovascular risk.

PMID- 19847000
TI  - Opsoclonus myoclonus: a non-epileptic movement disorder that may present as
      status epilepticus.
AB  - We describe two cases of a non-epileptic florid movement disorder presenting as
      status epilepticus. Both patients presented with florid jerking of the limbs and
      eyes. Convulsive status epilepticus related to presumed meningitis or
      encephalitis was suspected in both cases. The patients received treatment for
      seizures, without resolution of the abnormal movements, resulting ultimately in
      anaesthetic, intubation and ventilation. EEGs showed no epileptic discharges. The
      diagnosis was opsoclonus myoclonus syndrome in both. One patient was treated with
      adrenocorticotropic hormone (40 IU/day), the other with prednisolone (4
      mg/kg/day) with rapid resolution of symptoms. Neither patient had an underlying
      neoplasm or infectious agent identified. To date, neither patient has suffered a
      relapse of symptoms nor does either show any sign of developmental delay. These
      cases show that the movements in opsoclonus myoclonus syndrome can be
      sufficiently florid to mimic convulsive status epilepticus. Video footage of both
      patients at the time of diagnosis is presented online.

PMID- 19847001
TI  - Low back pain: do not forget the sacroiliac joint!

PMID- 19847002
TI  - Question 1. Efficacy of vagal nerve stimulation in children with medically
      intractable epilepsy.

PMID- 19847003
TI  - Towards evidence based medicine for paediatricians.

PMID- 19847004
TI  - Question 2. Should an infant who is breastfeeding poorly and has a tongue tie
      undergo a tongue tie division?

PMID- 19847005
TI  - Question 3. Does the clinical finding of ear wax exclude the finding of otitis
      media?

PMID- 19847006
TI  - Decline of hospital admissions for MMR vaccinations in children with egg allergy.

PMID- 19847007
TI  - An audit of urine culture results in well infants attending a prolonged jaundice
      clinic.

PMID- 19847009
TI  - George Frederic Still.

PMID- 19847011
TI  - Three-year-old outcomes of a brief universal parenting intervention to prevent
      behaviour problems: randomised controlled trial.
AB  - OBJECTIVE: To determine whether a structured programme of parent anticipatory
      guidance 'Toddlers Without Tears,' delivered in universal primary care, can
      prevent preschool child behaviour problems. DESIGN: Cluster randomised controlled
      trial. SETTING/PARTICIPANTS: 40 primary care nursing centres (clusters) in
      metropolitan Melbourne, Australia. 733 English-speaking mothers of 6- to 7-month
      old infants consecutively recruited from well-child appointments; 589 (80%)
      retained at age 3 years. INTERVENTION: Parenting programme from age 8 to 15
      months, with two group sessions co-led by well-child providers and a parenting
      expert. The programme addressed normal behaviour development and offered
      strategies to increase desired and reduce unwanted behaviour. While 93% of
      intervention parents received at least some of the programme, only 49% completed
      all components. Control Usual primary care. MAIN OUTCOME MEASURES: Maternal
      report of child externalising behaviour (Child Behaviour Checklist), parenting
      (Parent Behaviour Checklist) and maternal mental health (Depression Anxiety
      Stress Scales) when children were aged 3 years. RESULTS: Behaviour scores in the
      intervention and control groups were similar (mean (SD)) 11.4 (7.1) versus 12.4
      (7.6); adjusted mean difference -0.8, 95% CI -2.2 to 0.6, p=0.26). On the
      parenting subscale scores, intervention parents reported fewer unreasonable
      expectations of child development (37.3 (10.9) vs 39.9 (10.2), adjusted mean
      difference -3.1, 95% CI -4.9 to -1.4, p=0.001). The mean scores for harsh/abusive
      and nurturing parenting, and maternal mental health, were similar between the two
      groups. CONCLUSIONS: A brief universal parenting programme in primary care is
      insufficient to prevent development of preschool externalising problems. A new
      population trial targeting more intensive prevention to distressed parents with
      toddler behaviour problems is now under way, aiming to prevent externalising and
      internalising problems before school entry. TRIAL REGISTRATION NUMBER:
      ISRCTN77531789.

PMID- 19847012
TI  - Thioredoxin-interacting protein (Txnip) is a feedback regulator of S
      nitrosylation.
AB  - Nitric oxide exerts a plethora of biological effects via protein S-nitrosylation,
      a redox-based reaction that converts a protein Cys thiol to a S-nitrosothiol.
      However, although the regulation of protein S-nitrosylation has been the subject
      of extensive study, much less is known about the systems governing protein
      denitrosylation. Most recently, thioredoxin/thioredoxin reductases were shown to
      mediate both basal and stimulus-coupled protein denitrosylation. We now
      demonstrate that protein denitrosylation by thioredoxin is regulated dynamically
      by thioredoxin-interacting protein (Txnip), a thioredoxin inhibitor. Endogenously
      synthesized nitric oxide represses Txnip, thereby facilitating thioredoxin
      mediated denitrosylation. Autoregulation of denitrosylation thus allows cells to
      survive nitrosative stress. Our findings reveal that denitrosylation of proteins
      is dynamically regulated, establish a physiological role for thioredoxin in
      protection from nitrosative stress, and suggest new approaches to manipulate
      cellular S-nitrosylation.

PMID- 19847014
TI  - Liver allograft pathology: approach to interpretation of needle biopsies with
      clinicopathological correlation.
AB  - The spectrum of diseases encountered in post-transplant liver pathology biopsies
      is broad. In this review, these have been divided as belonging to one of three
      categories: (1) new-onset/de novo post-transplant abnormalities (early and late),
      (2) rejection, and (3) recurrence of original disease. The clinical and
      pathological features of the entities making up each category, with the relevant
      differential diagnosis and overlaps between and within these groups, are
      discussed and illustrated. Recurrent or de novo neoplasms make up a fourth
      category not included in this review. Early new-onset conditions are mostly
      related to surgical complications, donor factors and ischaemia to the graft.
      These include reperfusion/preservation injury, lipopeliosis, small-for-size
      syndrome, biliary sludge syndrome and hepatic artery thrombosis. The various
      forms of rejection (cellular, chronic, antibody-mediated, and late atypical
      rejection) are detailed. Most chronic liver diseases can and do recur in the
      graft. They may display features that overlap with de novo conditions (eg,
      primary sclerosing cholangitis versus chronic rejection). As with most cases of
      allograft biopsy interpretation, accurate diagnosis rests with careful
      correlation of histological features with clinical, imaging and laboratory
      findings, and often comparison with previous sequential and follow-up biopsies.
      Late-onset new diseases include biliary strictures, idiopathic chronic hepatitis
      and de novo autoimmune hepatitis, among others. This review provides a practical
      approach to the interpretation of these challenging biopsies. Selected difficult
      scenarios or conundrums are identified and discussed in the relevant sections.

PMID- 19847015
TI  - Radiochromic leuco dye micelle hydrogels: II. Low diffusion rate leuco crystal
      violet gel.
AB  - Radiation-sensitive hydrogels offer the capability of verifying intricate dose
      distributions in three-dimensional (3D) space conveniently in a single
      measurement with sub-millimetre spatial resolution. In this study, a new
      radiochromic hydrogel called leuco crystal violet (LCV) micelle gel is
      introduced. Upon irradiation, LCV converts to crystal violet (CV(+)). Triton X
      100 micelles are used to provide the required hybrid-interfacing environment to
      dissolve LCV. The diffusion coefficient of the LCV gel has been measured to be
      0.036 +/- 0.001 mm(2) h(-1), which is a factor of 25 times less than the standard
      radiochromic ferrous xylenol-orange (FX) gel; LCV gels without Triton X-100
      micelles have a diffusion coefficient of 0.33 +/- 0.02 mm(2) h(-1). The LCV gel
      formulation contains: 1 mM LCV, 25 mM trichloroacetic acid, 4 mM Triton X-100 and
      4% w/w gelatin. The primary innovative feature of this 3D hydrogel is that the
      radiation-induced CV(+) dye is more soluble in the Triton X-100 micelles than in
      the surrounding water which consequently leads to more stable post-irradiation
      dose distributions. A dosimetric characterization revealed that the dose response
      is reproducible to within 1% over three separate batches, independent of energy,
      dose rate and dose fractionation but is affected by the temperature (
      approximately 4% per degree C) during irradiation. LCV micelle gels scanned
      optically with a yellow light source are a promising system for 3D dose
      verification. They may prove to be, especially, useful for scanning large volume
      dosimeters (i.e. 20 cm) since they are easily manufactured, transparent and near
      colourless prior to irradiation.

PMID- 19847013
TI  - Regulation by glutathionylation of isocitrate lyase from Chlamydomonas
      reinhardtii.
AB  - Post-translational modification of protein cysteine residues is emerging as an
      important regulatory and signaling mechanism. We have identified numerous
      putative targets of redox regulation in the unicellular green alga Chlamydomonas
      reinhardtii. One enzyme, isocitrate lyase (ICL), was identified both as a
      putative thioredoxin target and as an S-thiolated protein in vivo. ICL is a key
      enzyme of the glyoxylate cycle that allows growth on acetate as a sole source of
      carbon. The aim of the present study was to clarify the molecular mechanism of
      the redox regulation of Chlamydomonas ICL using a combination of biochemical and
      biophysical methods. The results clearly show that purified C. reinhardtii ICL
      can be inactivated by glutathionylation and reactivated by glutaredoxin, whereas
      thioredoxin does not appear to regulate ICL activity, and no inter- or
      intramolecular disulfide bond could be formed under any of the conditions tested.
      Glutathionylation of the protein was investigated by mass spectrometry analysis,
      Western blotting, and site-directed mutagenesis. The enzyme was found to be
      protected from irreversible oxidative inactivation by glutathionylation of its
      catalytic Cys(178), whereas a second residue, Cys(247), becomes artifactually
      glutathionylated after prolonged incubation with GSSG. The possible functional
      significance of this post-translational modification of ICL in Chlamydomonas and
      other organisms is discussed.

PMID- 19847016
TI  - Radiochromic leuco dye micelle hydrogels: I. Initial investigation.
AB  - This investigation reports the use of surfactants and colorless leuco
      triarylmethane dyes to form a new class of radiochromic micelle hydrogels for
      three-dimensional (3D) water-equivalent dosimetry. Gelatin gel samples with
      several surfactants and leuco dyes were prepared and evaluated for optical
      transparency, dose sensitivity and diffusion rates. The addition of Triton X-100,
      a non-ionic surfactant, at levels exceeding the critical micelle concentration
      provides a transparent hydrogel in which the water insoluble leuco Malachite
      Green (LMG) can dissolve. During irradiation, the LMG dye precursor converts to
      Malachite Green (MG(+)). The most sensitive reported LMG gel formulation contains
      0.3 mM LMG leuco dye, 16 mM trichloroacetic acid, 7 mM Triton X-100 and 4% w/w
      gelatin. A diffusion coefficient of 0.14 mm(2) h(-1) was determined for MG(+) in
      this gel by fitting the time-dependent degradation of the transmission profile
      after irradiating half of the sample. The diffusion rate was three times lower
      than the standard radiochromic ferrous xylenol-orange (FX) gel. The primary
      feature of this 3D hydrogel is that it introduces transparent, radiochromic,
      micelle hydrogels. The radiochromic response to dose is instantaneous and images
      are stable for several hours. A dosimetric characterization revealed that the
      dose response is reproducible to within 10% over five separate batches and
      independent of both energy and dose rate. Uniform pre-irradiation of samples to 5
      Gy provided a subsequent near linear response to greater than 110 Gy. LMG gels
      when read with a fast optical CT scanner can provide full 3D dose distributions
      in less than 30 min post-irradiation. LMG micelle gels scanned with a 633 nm
      light source are a promising system for quantitative water- or tissue-equivalent
      3D dose verification in the 5-100 Gy dose range. These gels are useful for the
      scanning of larger volume dosimeters (i.e. >15 cm diameter) since they are easily
      prepared with inexpensive ingredients, are transparent and have a low initial
      optical absorbance prior to irradiation. In this gel, only one colored molecular
      species is produced. This results in a linear relation between the concentration
      of the colored dye product and optical absorption independent of the sampled
      wavelength.

PMID- 19847017
TI  - An alternative method for noise analysis using pixel variance as part of quality
      control procedures on digital mammography systems.
AB  - According to the European Guidelines for quality assured breast cancer screening
      and diagnosis, noise analysis is one of the measurements that needs to be
      performed as part of quality control procedures on digital mammography systems.
      However, the method recommended in the European Guidelines does not discriminate
      sufficiently between systems with and without additional noise besides quantum
      noise. This paper attempts to give an alternative and relatively simple method
      for noise analysis which can divide noise into electronic noise, structured noise
      and quantum noise. Quantum noise needs to be the dominant noise source in
      clinical images for optimal performance of a digital mammography system, and
      therefore the amount of electronic and structured noise should be minimal. For
      several digital mammography systems, the noise was separated into components
      based on the measured pixel value, standard deviation (SD) of the image and the
      detector entrance dose. The results showed that differences between systems
      exist. Our findings confirm that the proposed method is able to discriminate
      systems based on their noise performance and is able to detect possible quality
      problems. Therefore, we suggest to replace the current method for noise analysis
      as described in the European Guidelines by the alternative method described in
      this paper.

PMID- 19847018
TI  - Cerenkov radiation imaging as a method for quantitative measurements of beta
      particles in a microfluidic chip.
AB  - It has been observed that microfluidic chips used for synthesizing (18)F-labeled
      compounds demonstrate visible light emission without nearby scintillators or
      fluorescent materials. The origin of the light was investigated and found to be
      consistent with the emission characteristics from Cerenkov radiation. Since (18)F
      decays through the emission of high-energy positrons, the energy threshold for
      beta particles, i.e. electrons or positrons, to generate Cerenkov radiation was
      calculated for water and polydimethylsiloxane (PDMS), the most commonly used
      polymer-based material for microfluidic chips. Beta particles emitted from (18)F
      have a continuous energy spectrum, with a maximum energy that exceeds this energy
      threshold for both water and PDMS. In addition, the spectral characteristics of
      the emitted light from (18)F in distilled water were also measured, yielding a
      broad distribution from 300 nm to 700 nm, with higher intensity at shorter
      wavelengths. A photograph of the (18)F solution showed a bluish-white light
      emitted from the solution, further suggesting Cerenkov radiation. In this study,
      the feasibility of using this Cerenkov light emission as a method for
      quantitative measurements of the radioactivity within the microfluidic chip in
      situ was evaluated. A detector previously developed for imaging microfluidic
      platforms was used. The detector consisted of a charge-coupled device (CCD)
      optically coupled to a lens. The system spatial resolution, minimum detectable
      activity and dynamic range were evaluated. In addition, the calibration of a
      Cerenkov signal versus activity concentration in the microfluidic chip was
      determined. This novel method of Cerenkov radiation measurements will provide
      researchers with a simple yet robust quantitative imaging tool for microfluidic
      applications utilizing beta particles.

PMID- 19847019
TI  - Device variability and circuit redundancy in signal processing based on
      nanoswitches.
AB  - Signal processing based on molecular switches whose conductance can be tuned by
      an external stimulus between two (on and off) states has been proposed recently
      (Cervera et al 2008 J. Appl. Phys. 104 084317). The basic building block is a
      metal nanoparticle linked to two electrodes by an organic ligand and a
      nanoswitch. The net charge delivered by this nanostructure exhibits a sharp
      resonance when the alternating potential applied between the electrodes has the
      same frequency as the periodic variation between the on and off conductance
      states induced on the nanoswitch. This resonance can be used to process an
      external signal by selectively extracting the weight of the different harmonics.
      However, because of the fabrication process at the nanoscale, the nanostructures
      will show a significant variability in the physical characteristics. By using a
      phenomenological model that includes this variability, the stochastic nature of
      electron transference, and the thermal noise, we demonstrate that reliable signal
      processing can still be achieved by adapting the number of nanoswitches per bit
      of information (circuit redundancy) to the nanostructure tolerance (device
      variability). Extensive kinetic Monte Carlo simulations show that a moderate
      level of redundancy can compensate for significant nanostructure variability.
      This result gives support to the concept of ensembles of redundant switches as
      reliable components for signal processing at the nanoscale.

PMID- 19847020
TI  - Inverted hemispherical mask colloidal lithography.
AB  - This paper presents a cost-effective nanofabrication method for forming large
      area and high coverage two-dimensional metal nanostructures on flat and curved
      surfaces. This method starts with a periodic array of hemispherical dimples on
      polystyrene (PS) film prepared by colloidal lithography with a sacrificial layer
      of polyacrylic acid (PAA) underneath. After the removal of PAA in water solution,
      the PS layer is turned over and attached to the substrate to be patterned. An
      inverted hemispherical mask is formed after oxygen plasma etching. As the holes
      at the bottom are much larger than those on the surface, the mask is especially
      suitable for a standard lift-off process. Based on this mask, metal nano-disk and
      pair-disk arrays, as well as two-dimensional nanostructures on a curved surface,
      have been fabricated. Optical measurement shows that a surface plasmon resonance
      exists in a periodic disk array. This method is valuable for the fabrication of a
      magnifying metamaterial hyperlens in order to eliminate the limitation of optical
      diffraction.

PMID- 19847021
TI  - Nanolayer biofilm coated on magnetic nanoparticles by using a dielectric barrier
      discharge glow plasma fluidized bed for immobilizing an antimicrobial peptide.
AB  - Using the monomer of acrylic acid and the novel technique of using a dielectric
      barrier discharge glow plasma fluidized bed (GPFB), a nanolayer biofilm of
      polyacrylic acid (PAA) was uniformly coated on the surface of magnetic nickel
      nanoparticles (NPs). Transmission electron microscopy, Fourier transform infrared
      spectroscopy, and x-ray photoelectron spectroscopy, etc, were used to
      characterize the modified NPs. The thickness of the biofilm was about 2 nm when
      the NPs were treated using the GPFB once, and the discharging conditions affected
      the density of the carboxyl group obviously. The PAA acting as an adhesion layer
      was used to immobilize the antimicrobial peptide LL-37, to kill the bacteria of
      Escherichia coli (E. coli), and the results indicated that the modified nickel
      NPs immobilizing a certain concentration of LL-37 could kill the bacteria
      effectively.

PMID- 19847022
TI  - One-pot green synthesis of biocompatible arginine-stabilized magnetic
      nanoparticles.
AB  - A green one-step approach has been developed for the synthesis of amino
      functionalized magnetite nanoparticles. The synthesis was accomplished by simply
      mixing FeCl2 with arginine under ambient conditions. It was found that the
      Fe2+/arginine molar ratio, reaction duration and temperature greatly influence
      the size, morphology and composition of magnetic nanoparticles. The arginine
      stabilized magnetic nanoparticles were characterized by transmission electron
      microscopy, x-ray diffraction, x-ray photoelectron spectroscopy,
      thermogravimetric analysis, and Fourier transform infrared spectroscopy
      techniques. The results show that the prepared nanoparticles are spherically
      shaped with a nearly uniform size distribution and pure magnetite phase. The
      presence of arginine on the magnetic nanoparticle surface has been confirmed and
      the amount of surface arginine varies with the Fe2+/arginine molar ratio. The
      surface amine densities are calculated to be 5.60 and 7.84 micromol mg(-1) for
      magnetic nanoparticles prepared at 1:1 and 1:2 Fe2+/arginine molar ratio,
      respectively. The as-synthesized nanoparticles show superparamagnetic behavior at
      room temperature and good solubility in water. In addition, using a similar
      synthesis procedure, we have been able to synthesize superparamagnetic manganese
      and cobalt ferrite nanoparticles.

PMID- 19847023
TI  - Increased short circuit current in organic photovoltaic using high-surface area
      electrode based on ZnO nanowires decorated with CdTe quantum dots.
AB  - A photosensitized high-surface area transparent electrode has been employed to
      increase the short circuit current of a photovoltaic device with a blend of
      poly(3-hexylthiophene) (P3HT) and (6,6)-phenyl C61 butyric acid methyl ester
      (PCBM) as the active layer. This is achieved by directly growing ZnO nanowires on
      indium tin oxide (ITO) film via a physical vapor method. The nanowire surface is
      then decorated with CdTe quantum dots by pulsed electron-beam deposition (PED).
      The nanowires alone provided a 20-fold increase in the short circuit current
      under visible light illumination. This was further increased by a factor of
      approximately 1.5 by the photosensitization effect of CdTe, which has an optical
      absorption of up to 820 nm.

PMID- 19847024
TI  - Self-limited self-perfection by liquefaction for sub-20 nm trench/line
      fabrication.
AB  - We proposed and demonstrated a new approach to pressed self-perfection by
      liquefaction (P-SPEL), where a layer of SiO2 is used as a stopper on one sidewall
      of gratings, to self-limit the final trench width in P-SPEL to a preset stopper
      layer thickness, allowing a precise control of the final trench width without the
      need to control any pressing parameters such as pressure, temperature and the gap
      between the pressing plate and the substrate. We achieved 20 nm wide trenches
      from a 90 nm original width, reducing the original trench by 450%. We also
      observed improvement in the trench width uniformity. Using the fabricated resist
      trenches as templates, 20 nm metal lines were achieved by lift-off.

PMID- 19847025
TI  - A GaAs nanowire/P3HT hybrid photovoltaic device.
AB  - Hybrid solar cells with an energy conversion efficiency of 1.04% were fabricated
      by spin-coating poly(3-hexylthiophene) (P3HT) polymer onto vertically aligned n
      type GaAs nanowire arrays synthesized by molecular beam epitaxy. Experimental
      parameters such as the P3HT solvent mixing ratio of chlorobenzene to
      dichlorobenzene and nanowire surface etching were studied with a view to
      improving the energy conversion efficiency.

PMID- 19847026
TI  - Observation of plasmonic dipolar anti-bonding mode in silver nanoring structures.
AB  - We report on a clear experimental observation of the plasmonic dipolar anti
      bonding resonance in silver nanorings. The data can be explained effectively by
      the plasmon hybridization model, which is confirmed by the numerical calculations
      of the electromagnetic field and surface charge distribution profiles. The
      experimental demonstration of the plasmon hybridization model indicates its
      usefulness as a valuable tool to understand, design and predict optical
      properties of metallic nanostructures.

PMID- 19847027
TI  - Cosserat curve model for superelasticity of helices.
AB  - Superelasticity behavior of helices has been the focus of recent research in
      micro-/nano-engineering, while the traditional Kirchhoff rod model restricts
      itself in the bending and torsion conditions. With the aid of the concept of a
      Cosserat curve, a novel theoretical basis has been established for statics and
      dynamics of helices with essential extension and shear, which is able to
      quantitatively analyze the superelastic mechanical properties. Except for a good
      agreement with the experimental observation, numerical solutions have shown that
      we cannot only predict two important properties of the superelasticity
      characteristics: the breaking force and the stretch of the coil wire under the
      axial loading, but also precisely describe and explain the Hooke's constant and
      torque in the entire stretching and breaking processes. The present work has
      provided useful information for the future experimental investigation on
      superelasticity as well as its application in meta-/quantum devices.

PMID- 19847028
TI  - Friction-induced nanofabrication on monocrystalline silicon.
AB  - Fabrication of nanostructures has become a major concern as the scaling of device
      dimensions continues. In this paper, a friction-induced nanofabrication method is
      proposed to fabricate protrusive nanostructures on silicon. Without applying any
      voltage, the nanofabrication is completed by sliding an AFM diamond tip on a
      sample surface under a given normal load. Nanostructured patterns, such as linear
      nanostructures, nanodots or nanowords, can be fabricated on the target surface.
      The height of these nanostructures increases rapidly at first and then levels off
      with the increasing normal load or number of scratching cycles. TEM analyses
      suggest that the friction-induced hillock is composed of silicon oxide, amorphous
      silicon and deformed silicon structures. Compared to the tribochemical reaction,
      the amorphization and crystal defects induced by the mechanical interaction may
      have played a dominating role in the formation of the hillocks. Similar to other
      proximal probe methods, the proposed method enables fabrication at specified
      locations and facilitates measuring the dimensions of nanostructures with high
      precision. It is highlighted that the fabrication can also be realized on
      electrical insulators or oxide surfaces, such as quartz and glass. Therefore, the
      friction-induced method points out a new route in fabricating nanostructures on
      demand.

PMID- 19847029
TI  - Solution-processed flexible ZnO transparent thin-film transistors with a polymer
      gate dielectric fabricated by microwave heating.
AB  - We report the development of solution-processed zinc oxide (ZnO) transparent thin
      film transistors (TFTs) with a poly(2-hydroxyethyl methacrylate) (PHEMA) gate
      dielectric on a plastic substrate. The ZnO nanorod film active layer, prepared by
      microwave heating, showed a highly uniform and densely packed array of large
      crystal size (58 nm) in the [002] direction of ZnO nanorods on the plasma-treated
      PHEMA. The flexible ZnO TFTs with the plasma-treated PHEMA gate dielectric
      exhibited an electron mobility of 1.1 cm(2) V(-1) s(-1), which was higher by a
      factor of approximately 8.5 than that of ZnO TFTs based on the bare PHEMA gate
      dielectric.

PMID- 19847030
TI  - Synthesis of SnO2-ZnO core-shell nanofibers via a novel two-step process and
      their gas sensing properties.
AB  - SnO2-ZnO core-shell nanofibers were synthesized via a novel two-step process.
      First, SnO2 nanofibers were synthesized by electrospinning. In sequence, ZnO
      shell layers were deposited using atomic layer deposition on the electrospinning
      synthesized SnO2 nanofibers. To demonstrate the practical applications of the
      synthesized core-shell nanofibers, we investigated their sensing properties to O2
      and NO2. The high sensitivity and dynamic repeatability observed in these sensors
      reveal that the core-shell nanofibers are promising as sensitive and reliable
      chemical sensors.

PMID- 19847031
TI  - Temperature-induced restructuring of self-assembled PtPd nanoparticle
      superlattices.
AB  - PtPd nanoparticle superlattices were prepared at room temperature and
      investigated for their restructuring at elevated temperatures. The PtPd
      nanoparticles were spherical with a diameter of 3.5 +/- 0.3 nm and were capped
      with surfactants of oleic acids and oleylamine. Images of the nanoparticle
      superlattices were taken using a transmission electron microscope. Analysis of
      the images with fast Fourier transform (FFT) revealed whether the superlattices
      were crystalline or amorphous. It was found that the critical temperature that
      induced a phase transition of PtPd superlattices from a crystalline state to an
      amorphous state falls in the range of 100-110 degrees C. Meanwhile, heat-induced
      restructuring transformed less-ordered superlattices into better-ordered ones,
      similar to annealing. It was especially pronounced for 3D superlattices, which
      also showed well-defined grain boundaries after restructuring.

PMID- 19847032
TI  - The formation of vertically aligned biaxial tungsten nanorods using a novel
      shadowing growth technique.
AB  - Biaxially textured tungsten nanorods (A15 crystal structure) have been grown by
      oblique angle DC magnetron sputtering using a novel rotation mode called 'two
      step rotation'. In this mode, the substrate is given a fast rotation through 180
      degrees at 90 rpm and this is followed by a rest period of 30 s. These nanorods
      are vertically aligned and have a [100] texture normal to the substrate along
      with preferential in-plane texture as shown by x-ray pole figure analysis. In
      contrast, the tungsten nanorods obtained without substrate rotation are slanted
      at an angle of approximately 45 degrees and have a [100] texture tilted 16
      degrees with respect to the substrate normal. The flux is incident from two
      diametrically opposite points on the sample at an oblique angle, averaging out
      the growth into vertical columns that retain the in-plane texture. Scanning
      electron microscopy shows that the tungsten nanorods have a mixture of {211} and
      {421} crystal habits; these planes are both minimum surface energy planes for a
      cubic A15 crystal structure.

PMID- 19847033
TI  - Ideal strength on clusters from first principles: the Ti(13) case.
AB  - The mechanical behavior of a Ti(13) cluster, based on total energy mechanical
      quantum calculations is studied. The cluster geometry has been optimized and good
      agreement with previous reports has been found. Axial strain is applied along one
      of the principal axes and the changes on the energetic and vibrational properties
      of the system are followed. To characterize the cluster stability as a function
      of strain, vibrational frequencies and total energy have been calculated, to
      obtain the cluster maximum load tolerance for compression (C) and tensile (T). If
      the maximum load is defined through a vibrational instability, it happens to be
      two and half, and three times larger than when the maximum total energy is
      considered (C and T respectively). As a result of the induced strain along of the
      C(5) symmetry element, the cluster changes its point group symmetry from I(h) to
      D(5d), with an energy difference of 1.17 eV (for compression) and 0.33 eV (for
      tension) with respect to the ground state geometry. The electronic changes are
      also characterized, as function of the strain, by following the modifications of
      the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular
      orbital (LUMO) and changes on the total atomic population.

PMID- 19847034
TI  - A method of fabricating highly transparent and conductive interpenetrated carbon
      nanotube-parylene networks.
AB  - We report a method of fabrication of free standing and ultra-thin carbon nanotube
      parylene-C interpenetrating networks. The network is highly transparent, highly
      flexible, and more conductive than transparent nanotube/polymer composites.
      Scanning electron microscope imaging reveals that the interpenetrated networks
      are dense and pinhole free compared to bare nanotube networks. We found that
      parylene-C coats along carbon nanotubes and links them together, increasing both
      the mechanical robustness of the film, and the electrical stability under UV
      radiation. This method is universal for fabricating interpenetrating networks of
      other nanoscale materials such as nanowires and nanofibers.

PMID- 19847035
TI  - Quantum tunneling in nanomagnetic systems with different uniaxial anisotropy
      order.
AB  - A study of macroscopic quantum tunneling (MQT) of the magnetic moment in systems
      with quadratic and higher order uniaxial anisotropy and Zeeman interaction is
      presented. By using the instanton technique, under the giant spin approximation,
      the escape rate or probability per unit of time Gamma that the system undergoes a
      transition between coherent or metastable states is calculated. Using an
      effective particle potential we also determine the escape temperature T(e)(T),
      which marks the transition from quantum tunneling to thermal activation. A
      discussion is presented about the different models and the behavior of the
      magnetic system under the tunneling regime.

PMID- 19847036
TI  - Dramatic property enhancement in polyetherimide using low-cost commercially
      functionalized multi-walled carbon nanotubes via a facile solution processing
      method.
AB  - Polyetherimide (PEI) has excellent mechanical and thermal properties, and
      exceptional fire resistance. Developing even broader multi-functionality in
      PEI/carbon nanotube (CNT) composites for industrial applications is an alluring
      but challenging goal, due to processing difficulties related to the high pressure
      and temperature needed to achieve effective flow for this polymer, and costly and
      complex treatments of the CNTs. Here we report the fabrication of PEI
      nanocomposite films using low-cost commercially functionalized multi-walled
      carbon nanotubes (MWNTs), and a simple and innovative process, achieving
      exceptional properties with only 0.5 wt% of MWNTs, including an increase in
      electrical conductivity of 12 orders of magnitude, accompanied by an
      unprecedented increase of 86 degrees C in thermal decomposition temperature
      (higher service temperature). Field emission scanning electron microscopy
      revealed a high degree of uniform dispersion among the MWNTs, superb polymer-MWNT
      interaction and formation of a spatially homogeneous nanotube network within the
      matrix. The enhancement in these properties suggests great potential use for this
      developed processing approach and the resulting nanocomposites for multi
      functional coating or interfacing materials in aerospace and electronic
      industries.

PMID- 19847037
TI  - Stable Nafion-functionalized graphene dispersions for transparent conducting
      films.
AB  - Nafion was used for the first time to aid in preparing stable graphene
      dispersions in mixed water/ethanol (1:1) solvents via the reduction of graphite
      oxide using hydrazine. The dispersion was characterized by ultraviolet-visible
      (UV-vis) spectra, transmission electron microscopy, zeta potential analysis, etc.
      It was found that for Nafion-to-graphene ratios higher than 5:1, graphene
      solutions with concentrations up to 1 mg ml(-1) and stabilities of over three
      months were obtained. It was proposed that the Nafion adsorbed onto the graphene
      by the hydrophobic interaction of its fluoro-backbones with the graphene layer
      and imparted stability by an electrosteric mechanism. Furthermore, transparent
      and conductive films were prepared using these highly stable Nafion-stabilized
      graphene dispersions. The prepared Nafion-graphene films possess smooth and
      homogeneous surfaces and the sheet resistance was as low as 30 kOmega/sq for a
      transmittance of 80% at 550 nm, which was much lower than for other graphene
      films obtained by chemical reduction. X-ray photoelectron spectroscopy and Raman
      spectroscopy confirmed the p-doping of the graphene by Nafion. It was expected
      that this p-doping effect, as well as the high dispersing ability of Nafion for
      graphene and the connection of the sp(2) domains by residual Nafion combined to
      produce good properties of the Nafion-graphene films.

PMID- 19847038
TI  - Dewetting of copper nanolayers on silica in oxygen: towards preparation of copper
      meso/nanowires by self-organization.
AB  - The present study has examined the thermal behavior of copper on silicon oxide to
      clarify the diffusion of copper on dielectrics in an oxygen environment. Films of
      copper-deposited silicon oxide were prepared on silicon wafers and then annealed
      in oxygen. Self-organization of copper occurred to form line structures of
      multiple strips in a specific oxygen pressure range. The line orientation of the
      produced structures was related to the line defects formed from termination of
      stacking faults and dislocations at the wafer surface. The line density was
      determined by the oxygen pressure used. The results underline a possibility of
      synthesizing copper meso/nanowires on dielectrics via self-organization.

PMID- 19847039
TI  - Alzheimer's disease. Introduction.

PMID- 19847040
TI  - Structural neuroimaging in the detection and prognosis of pre-clinical and early
      AD.
AB  - Current research supports the strong potential of structural MRI profiles, even
      within cross-sectional designs, as a promising method for the discrimination of
      Alzheimer's Disease (AD) from normal controls and for the prediction of Mild
      Cognitive Impairment (MCI) progression and conversion to AD. Findings suggest
      that measures of structural change in mesial and lateral temporal, cingulate,
      parietal and midfrontal areas may facilitate the assessment of a treatment's
      ability to halt the progressive structural loss that accompanies clinical decline
      in MCI. The performance of prediction is likely to continue to improve with the
      incorporation of measures from other neuroimaging modalities, clinical
      assessments, and neuromedical biomarkers, as the regional profile of individuals
      at risk for progression is refined.

PMID- 19847041
TI  - A comparative analysis of structural brain MRI in the diagnosis of Alzheimer's
      disease.
AB  - Dementia is a debilitating and life-altering disease which leads to both memory
      impairment and decline of normal executive functioning. While causes of dementia
      are numerous and varied, the leading cause among patients 60 years and older is
      Alzheimer's disease. The gold standard for Alzheimer's diagnosis remains
      histological identification of amyloid plaques and neurofibrillary tangles within
      the medial temporal lobe, more specifically the entorhinal cortex and
      hippocampus. Although no definitive cure for Alzheimer's disease currently
      exists, there are treatments targeted at preserving cognition and memory while
      delaying continued loss of function. Alzheimer's disease exists along a spectrum
      of cognitive decline and is often preceded by Mild Cognitive Impairment (MCI).
      Patients with MCI demonstrate memory loss and cognitive impairment while still
      continuing normal activities of daily living, and are considered to be at
      increased risk for developing Alzheimer's Dementia. Identifying patients with
      prodromal states of Alzheimer's dementia such as MCI may allow initiation of
      appropriate treatment planning and delay of cognitive decline. Therefore, the
      need for a non-invasive early biomarker for the detection of Alzheimer's disease
      has never been greater. Multiple neuroimaging methods utilizing visual rating
      scales, volumetric measurements, and automated methods have been developed to
      identify, quantify, and track anatomic sequelae of Alzheimer's Disease.

PMID- 19847042
TI  - Fully-automated volumetric MRI with normative ranges: translation to clinical
      practice.
AB  - Neurodegenerative disorders, such as Alzheimer's disease (AD), are associated
      with characteristic patterns of neuropathological spread in the brain. Disease
      progression is usually accompanied by regional atrophy that can be detected
      noninvasively using structural magnetic resonance imaging (MRI). A wealth of data
      has demonstrated the value of quantitative measurements of regional atrophy in
      AD, suggesting that volumetric MRI (vMRI) may be a useful clinical tool. vMRI
      provides biological evidence of neurodegenerative disease in patients with
      cognitive impairment. However, several hurdles impede implementation of vMRI in
      clinical practice. These include a lack of standardized MRI acquisition
      protocols, spatial distortions in MRI data, labor-intensive vMRI methods
      susceptible to interoperator variability, a lack of normative ranges for volume
      measures, and difficulty integrating vMRI in clinical workflow. Advances in vMRI
      have resulted from multi-institutional studies of brain imaging, such as the
      Alzheimer's Disease Neuroimaging Initiative (ADNI), and help address these
      challenges. New, fully-automated measures of brain structure volumes coupled with
      large, multi-center studies using standardized MRI protocols now allow the
      development of age-adjusted normative ranges for vMRI. Such advances are critical
      for providing physicians a framework for assessing the pattern and degree of
      regional atrophy in a patient's brain and applying vMRI in clinical practice.

PMID- 19847043
TI  - Cognitive phenotypes, brain morphometry and the detection of cognitive decline in
      preclinical AD.
AB  - Identifying a preclinical phase of Alzheimer's Disease (PCAD) that is distinct
      from cognitive changes in healthy aging continues to be a major research focus.
      Combining neuropsychological and neuroimaging methodologies should improve our
      ability to differentiate healthy from pathological aging, although studies that
      utilize both methods often result in equivocal findings, possibly due to
      variability in cognitive test performance that may be capturing distinct
      phenotypes. One method of capturing this cognitive variability is to utilize
      contrasting neuropsychological tests to identify subgroups representative of
      distinct cognitive phenotypes, and determine whether differences in brain
      morphometry support these classifications. We review several approaches to
      defining cognitive subgroups, and we consider the possibility that cognitive
      asymmetry might provide one means of identifying both functional and structural
      changes associated with aging and dementia.

PMID- 19847044
TI  - Diffusion tensor imaging in Alzheimer's disease and mild cognitive impairment.
AB  - Structural magnetic resonance imaging (MRI) studies of Alzheimer's disease and
      mild cognitive impairment (MCI) have focused on the hippocampus and entorhinal
      cortex; gray matter structures in the medial temporal lobe. Few studies have
      investigated the integrity of white matter in patients with AD or MCI. Diffusion
      tensor imaging (DTI) is a MRI technique that allows for the interrogation of the
      microstructural integrity of white matter. Based on increases in translational
      diffusion (mean diffusivity: MD) and decreases directional diffusion (fractional
      anisotropy: FA) damage to white matter can be assessed. Studies have identified
      regions of increased MD and decreased FA in patients with AD and MCI in all lobes
      of the brain, as well as medial temporal lobe structures including the
      hippocampus, entorhinal cortex and parahippocampal white matter. The pattern of
      white matter integrity disruption tends to follow an anterior to posterior
      gradient with greater damage noted in posterior regions in AD and MCI. Recent
      studies have exploited inter-voxel directional similarities to develop models of
      white matter pathways, and have used these models to assess the integrity of
      inter-cerebral connections. Particular focus has been applied to the
      parahippocampal white matter (including the perforant path) and the posterior
      cingulum. Although many studies have found DTI indicators of impaired white
      matter in AD and MCI, other studies have failed to detect any differences in MD
      or FA between the groups, demonstrating the need for large replicative studies.
      DTI is an evolving technique and advances in its application ought to provide new
      insights into AD and MCI.

PMID- 19847045
TI  - Changes in parahippocampal white matter integrity in amnestic mild cognitive
      impairment: a diffusion tensor imaging study.
AB  - In the present study, changes in the parahippocampal white matter (PWM), in the
      region that includes the perforant path, were investigated, in vivo, in 14
      individuals with amnestic mild cognitive impairment (aMCI) compared to 14 elderly
      controls with no cognitive impairment (NCI). For this purpose, (1) volumetry; (2)
      diffusion tensor imaging (DTI) derived measures of mean diffusivity (MD) and
      fractional anisotropy (FA); and (3) tractography were used. In addition,
      regression models were utilized to examine the association of PWM measurements
      with memory decline. The results from this study confirm previous findings in our
      laboratory and others, showing that compared to controls, individuals with aMCI
      have PWM volume loss. In addition to volume reduction, participants with aMCI
      demonstrated a significant increase in MD, but no difference in FA, both in the
      PWM region and in fibers modeled to pass through the PWM region. Further, the DTI
      metric of MD was associated with declarative memory performance, suggesting it
      may be a sensitive marker for memory dysfunction. These results indicate that
      there is general tissue loss and degradation (decreased volume; increased MD) in
      individuals with aMCI compared to older people with normal cognitive function.
      However, the microstructural organization of remaining fibers, as determined by
      measures of anisotropic diffusion, is not significantly different from that of
      controls.

PMID- 19847047
TI  - Functional MRI assessment of task-induced deactivation of the default mode
      network in Alzheimer's disease and at-risk older individuals.
AB  - Alzheimer's disease (AD) is the most common form of dementia in old age, and is
      characterized by prominent impairment of episodic memory. Recent functional
      imaging studies in AD have demonstrated alterations in a distributed network of
      brain regions supporting memory function, including regions of the default mode
      network. Previous positron emission tomography studies of older individuals at
      risk for AD have revealed hypometabolism of association cortical regions similar
      to the metabolic abnormalities seen in AD patients. In recent functional magnetic
      resonance imaging (fMRI) studies of AD, corresponding brain default mode regions
      have also been found to demonstrate an abnormal fMRI task-induced deactivation
      response pattern. That is, the relative decreases in fMRI signal normally
      observed in the default mode regions in healthy subjects performing a cognitive
      task are not seen in AD patients, or may even be reversed to a paradoxical
      activation response. Our recent studies have revealed alterations in the pattern
      of deactivation also in elderly individuals at risk for AD by virtue of their
      APOE e4 genotype, or evidence of mild cognitive impairment (MCI). In agreement
      with recent reports from other groups, these studies demonstrate that the pattern
      of fMRI task-induced deactivation is progressively disrupted along the continuum
      from normal aging to MCI and to clinical AD and more impaired in e4 carriers
      compared to non-carriers. These findings will be discussed in the context of
      current literature regarding functional imaging of the default network in AD and
      at-risk populations.

PMID- 19847046
TI  - Large-scale functional brain network abnormalities in Alzheimer's disease:
      insights from functional neuroimaging.
AB  - Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer's
      disease (AD) have begun to reveal abnormalities in large-scale memory and
      cognitive brain networks. Since the medial temporal lobe (MTL) memory system is a
      site of very early pathology in AD, a number of studies have focused on this
      region of the brain. Yet it is clear that other regions of the large-scale
      episodic memory network are affected early in the disease as well, and fMRI has
      begun to illuminate functional abnormalities in frontal, temporal, and parietal
      cortices as well in MCI and AD. Besides predictable hypoactivation of brain
      regions as they accrue pathology and undergo atrophy, there are also areas of
      hyperactivation in brain memory and cognitive circuits, possibly representing
      attempted compensatory activity. Recent fMRI data in MCI and AD are beginning to
      reveal relationships between abnormalities of functional activity in the MTL
      memory system and in functionally connected brain regions, such as the precuneus.
      Additional work with "resting state" fMRI data is illuminating functional
      anatomic brain circuits and their disruption by disease. As this work continues
      to mature, it will likely contribute to our understanding of fundamental memory
      processes in the human brain and how these are perturbed in memory disorders. We
      hope these insights will translate into the incorporation of measures of task
      related brain function into diagnostic assessment or therapeutic monitoring,
      which will hopefully one day be useful for demonstrating beneficial effects of
      treatments being tested in clinical trials.

PMID- 19847048
TI  - Pinpointing synaptic loss caused by Alzheimer's disease with fMRI.
AB  - During its earliest stage, before cell loss and independent of amyloid plaques
      and neurofibrillary tangles, Alzheimer's disease (AD) causes synaptic loss
      affecting the basal functional properties of neurons. In principle, synaptic loss
      can be detected by measuring AD-induced changes in basal function, or by
      measuring stimulus-evoked responses on top of basal changes. Functional magnetic
      resonance imaging (fMRI) is sensitive to both basal changes and evoked-responses,
      and there are therefore two experimental approaches in which fMRI can be used to
      pinpoint synaptic loss in AD. In this review, we will compare and contrast both
      approaches for pinpointing when and where synaptic loss in AD begins and for
      monitoring therapeutic efficacy.

PMID- 19847049
TI  - Diagnosis of Alzheimer's disease with [18F]PET in mild and asymptomatic stages.
AB  - With longer life expectancy, dementia based on the age-related Alzheimers'
      disease (AD) has turned into one of the most prevalent disorders of older age,
      representing a serious medical and socio-economic issue. There has been growing
      interest in early diagnosis of this disease, particularly regarding the
      initiation of new treatment strategies ahead of the onset of irreversible
      neuronal damage. It is accepted that the pathologic changes underlying AD appear
      in the brain years to decades before the symptomatic stages. Consequently,
      clinical measures of cognitive impairment, as used for definition of dementia,
      will not allow early diagnosis of AD-pathology in the mild or asymptomatic
      stages. Thus, a need for complementary sensitive biomarkers is apparent. Brain
      imaging markers are among the most promising candidates for this diagnostic
      challenge. Particularly, [18F]FDG PET as a marker of regional neuronal function
      has been demonstrated to represent a most sensitive and specific method for early
      identification of AD-pathology and thus for prediction of dementia of the
      Alzheimer type (DAT), even in the mild and asymptomatic stages. Currently,
      systematic data of comparable quality are hardly available for any other imaging
      procedure. The purpose of this article is to describe the typical findings of
      [18F]FDG PET in different stages of AD and to demonstrate its value for early and
      reliable diagnosis of Alzheimer's disease, particularly ahead of the stage of
      dementia of the Alzheimer's type.

PMID- 19847051
TI  - Applications of neuroimaging to disease-modification trials in Alzheimer's
      disease.
AB  - Critical to development of new therapies for Alzheimer's disease (AD) is the
      ability to detect clinical or pathological change over time. Clinical outcome
      measures typically used in therapeutic trials have unfortunately proven to be
      relatively variable and somewhat insensitive to change in this slowly progressive
      disease. For this reason, development of surrogate biomarkers that identify
      significant disease-associated brain changes are necessary to expedite treatment
      development in AD. Since AD pathology is present in the brain many years prior to
      clinical manifestation, ideally we want to develop biomarkers of disease that
      identify abnormal brain structure or function even prior to cognitive decline.
      Magnetic resonance imaging, fluorodeoxyglucose positron emission tomography, new
      amyloid imaging techniques, and spinal fluid markers of AD all have great
      potential to provide surrogate endpoint measures for AD pathology. The
      Alzheimer's disease neuroimaging initiative (ADNI) was developed for the distinct
      purpose of evaluating surrogate biomarkers for drug development in AD. Recent
      evidence from ADNI demonstrates that imaging may provide more sensitive, and
      earlier, measures of disease progression than traditional clinical measures for
      powering clinical drug trials in Alzheimer's disease. This review discusses
      recently presented data from the ADNI dataset, and the importance of imaging in
      the future of drug development in AD.

PMID- 19847052
TI  - Principles of ethical authorship for publication in Clinical Hemorheology and
      Microcirculation.

PMID- 19847053
TI  - Wavelet analysis of Laser Doppler Flux time series of tumor and inflammatory
      associated neoangiogenesis. Differences in rhythmical behavior.
AB  - We use continuous wavelet analysis (WA) of Laser Doppler Flux (LDF) time series
      measured in basal cell carcinomas (BCC) and plaque psoriasis (PP) in order to
      investigate the rhythmical behavior of blood flow in tumor or inflammatory
      associated neoangiogenesis.A total of 68 patients with primary BCCs and 40
      patients with PP were included in the study. LDF time series were separated in
      four scaling levels corresponding to the influences of sympathetic activity
      (SL1), myogenic activity in the vessel wall (SL2), respiration (SL3) and heart
      beat (SL4).In BCC, SL1 decreased compared to healthy skin. In all other scaling
      levels, we found a statistically significant increase of the SLs compared to
      healthy skin. These increases were not found in PP.Rhythmical behavior of blood
      flow in malignant tumors is totally different from that in regions with
      inflammation. In BCCs, thermoregulatory processes, ascribed to sympathetic
      activity, decrease statistically significant. In contrast, inflammatory processes
      in PP do not substantially change sympathetic activity. WA of tumor perfusion
      could open a new noninvasive monitor system for controlling tumor therapy.

PMID- 19847050
TI  - Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo.
AB  - Amyloid imaging represents a major advance in neuroscience, enabling the
      detection and quantification of pathologic protein aggregations in the brain. In
      this review we survey current amyloid imaging techniques, focusing on positron
      emission tomography (PET) with (11)carbon-labelled Pittsburgh Compound-B ((11)C
      PIB), the most extensively studied and best validated tracer. PIB binds
      specifically to fibrillar beta-amyloid (Abeta) deposits, and is a sensitive
      marker for Abeta pathology in cognitively normal older individuals and patients
      with mild cognitive impairment (MCI) and Alzheimer's disease (AD). PIB-PET
      provides us with a powerful tool to examine in vivo the relationship between
      amyloid deposition, clinical symptoms, and structural and functional brain
      changes in the continuum between normal aging and AD. Amyloid imaging studies
      support a model in which amyloid deposition is an early event on the path to
      dementia, beginning insidiously in cognitively normal individuals, and
      accompanied by subtle cognitive decline and functional and structural brain
      changes suggestive of incipient AD. As patients progress to dementia, clinical
      decline and neurodegeneration accelerate and proceed independently of amyloid
      accumulation. In the future, amyloid imaging is likely to supplement clinical
      evaluation in selecting patients for anti-amyloid therapies, while MRI and FDG
      PET may be more appropriate markers of clinical progression.

PMID- 19847054
TI  - Left ventricular geometry and rheological properties of erythrocytes in patients
      at cardiovascular disease risk.
AB  - The relationship between erythrocyte deformability and aggregability with left
      ventricular mass index has been examined in patients diagnosed with at least one
      cardiovascular risk factor but without ongoing coronary heart disease. The group
      consisted of 66 individuals, 30 men and 36 women, of the average age 57.7 years.
      For each patient, deformability and aggregability of red blood cells (RBCs) as
      well as end-diastolic left ventricle diameter (LVD), interventricular septum
      thickness (IVST) and posterior wall thickness (PWT) were measured. On the basis
      of the echocardiographical parameters and anthropometric data, left ventricular
      mass index (LVMI) was calculated. The analysis revealed statistically significant
      correlation between the LVMI and erythrocyte deformability and aggregability: the
      LVMI increases with decreasing deformability and is higher in patients with
      higher aggregability. This finding indicates that the worsening of RBC
      rheological properties is one of the main factors contributing to alterations of
      cardiac geometry through the increase of peripheral resistance which, in turn,
      significantly augments the heart afterload. Given that left ventricular
      hypertrophy (LVH) is a predictor of cardiovascular morbidity and mortality, the
      association between hemorheological parameters and left ventricular geometry may
      be important in clinical practice.

PMID- 19847055
TI  - The effect of carotid stenting on rheological parameters, free radical production
      and platelet aggregation.
AB  - INTRODUCTION: Carotid artery stenting has become a possible treatment of
      significant carotid stenosis. The risk of stent occlusion and restenosis might be
      increased by abnormal rheological conditions amplified platelet aggregation and
      free radical production during the operation. AIMS: The aim of our study was to
      assess the changes in hemorheological parameters, platelet aggregation, and
      catalase activity after endovascular treatment of carotid stenosis. METHODS: 18
      patients (11 men, ages 68 +/- 9 years and 7 women, ages 62 +/- 8 years) suffering
      from significant carotid stenosis and treated with carotid endovascular
      intervention were examined. Alteration in hemorheological parameters as well as
      epinephrine-, ADP-, and collagen-induced platelet aggregation were evaluated.
      Antioxidant reserve was characterized by the determination of catalase activity.
      The measurements were carried out directly before and after the procedure and 1,
      2, 5 days and 1 month following the intervention. Preceding the operation the
      patients were administered a maximum dose (300 mg) of clopidogrel. RESULTS:
      Hematocrit, plasma fibrinogen concentration (PFC) and whole blood-, and plasma
      viscosity values (WBV and PV) significantly decreased immediately after stenting
      (p<0.001). By the fifth day following the intervention the PFC, WBV, PV, red
      blood cell (RBC) aggregation and ADP-induced platelet aggregation significantly
      increased (p<0.0001) compared to values measured postprocedurally. At 1 month
      follow-up these parameters, except whole blood viscosity, decreased significantly
      compared to measurements made on the 5th day. On the other hand, catalase
      activity showed significant elevation by the end of the first month. CONCLUSION:
      Hemorheological parameters and platelet aggregation showed specific changes
      following carotid stenting. Abnormal changes of the rheological conditions and
      increasing platelet activation are the most pronounced in the first week
      following stenting, which may lead to early stent occlusion. Oxidative stress
      production returned to baseline levels only by the end of the first month.

PMID- 19847056
TI  - Impaired red cell deformability in iron deficient subjects.
AB  - Iron deficiency is a systemic disorder, which affects a variety of different cell
      types and is one of the most frequent diseases throughout the world. The
      influence of iron deficiency upon erythrocyte deformability is controversial and
      could be a consequence of membrane peroxidation damage or cross linking of
      membrane proteins. The aim of this study was to determine the overall elasticity
      (the deformability of the entire cell is evaluated) of iron deficient red blood
      cells (RBC) using laser optical tweezers. In this study, the laser trapped the
      cell and the elasticity was then analyzed measuring cell deformation at six
      different drag velocities. Twenty-five RBCs from 11 healthy blood donors
      (controls) and 7 patients with iron deficiency anemia were analyzed. Iron
      deficiency subjects were classified into 3 groups based on Hb concentration for
      statistical analysis (group I: Hb = 7.0-7.9; group II: 8.0-10.2 and group III:
      7.0-10.2 g/dl). The results showed an increased rigidity in the iron deficiency
      of deficient red blood cells when compared to normal control blood cells, and,
      this impaired deformability seems to be correlated to the hemoglobin
      concentration. In conclusion, the results obtained by optical tweezers showed
      that iron deficiency affects the elasticity of whole RBC.

PMID- 19847057
TI  - Lipid peroxidation and total antioxidant status in unprofessional athletes before
      and after a cardiopulmonary test.
AB  - We examined lipid peroxidation, expressed as thiobarbituric acid-reactive
      substances (TBARS) and total antioxidant status (TAS) before and after a
      cardiopulmonary test, in 20 sedentary controls and in 62 unprofessional male
      athletes subdivided into 3 subgroups. The first included subjects who practised
      endurance sports (14 cyclists and 9 endurance swimmers), the second subjects who
      practised mixed sports (6 basket players, 6 judoists, 8 water polo players) and
      the third group subjects who practised power sports (3 sprint runners, 4
      weightlifters, 12 sprint swimmers). In the whole group of athletes an increase in
      TBARS and a decrease in TAS were present at baseline. Subdividing the whole group
      into three subgroups we observed an increase in TBARS in all and a decrease in
      TAS only in the endurance and mixed athletes. After the test, TBARS showed a more
      significant increase in controls compared to the whole group and each subgroup of
      athletes, while TAS increased only in the whole group and in those who practised
      mixed sports. In conclusion, at baseline in athletes the oxidative status shows a
      different behaviour compared to controls, while after the test the antioxidant
      protection is more marked and it may be related to an increase of antioxidant
      systems.

PMID- 19847058
TI  - Quantification of the erythrocyte deformability using atomic force microscopy:
      correlation study of the erythrocyte deformability with atomic force microscopy
      and hemorheology.
AB  - Atomic force microscope (AFM) is a powerful and prospective tool in the studies
      of the cellular deformability within a single cell. However, the reliability of
      using AFM in estimating the cellular average deformability was suspected.
      Hemorheology, one of common clinical examinations, can assess the deformability
      of erythrocytes. In order to validate the reliability in estimating the cellular
      deformability with AFM, the correlation was studied between the stiffness of the
      erythrocyte membrane with AFM and the deformation index with the hemorheology
      test. Blood samples were taken from 5 diabetes mellitus patients and 5 healthy
      non-obese people. The erythrocyte deformability was detected by AFM and the
      hemorheology test, respectively. Excellent correlation (r=0.907, p=0.000<0.01)
      was found between the average erythrocyte stiffness with AFM and the deformation
      index obtained from the hemorheology test. Besides, it was found that the average
      stiffness and the deformation index of diabetes mellitus patients were
      significantly higher than those of healthy non-obese people (p=0.007 and
      p=0.003). The result was consistent with the impairment of erythrocytes form
      diabetes mellitus patients. Therefore, it is the first time that the
      quantification relation of the erythrocyte deformability was investigated with
      AFM and the hemorheology test, and the feasible and reliable were validated that
      AFM is used to investigate the mechanical properties of different living cells
      qualitatively and quantitatively.

PMID- 19847059
TI  - Elastase, myeloperoxidase, nitric oxide metabolites and oxidative status in
      subjects with clinical stable chronic renal failure on conservative treatment.
AB  - We evaluated, in a group of 41 CRF undialyzed subjects (29 men and 12 women, mean
      age 64.1 +/- 11.3 years), some parameters that reflect leukocyte activation
      (elastase, myeloperoxidase - MPO), plasma NO metabolites (NO(x)) and the
      oxidative status (lipid peroxidation expressed as thiobarbituric acid-reactive
      substances (TBARS) and total antioxidant status (TAS). Elastase was determined,
      on plasma separated from fasting venous blood, as elastase/alpha1-proteinase
      inhibitor complex. MPO was evaluated employing the Myeloperoxidase ELISA kit. The
      NO production was evaluated by a micromethod. The oxidation of polyunsaturated
      fatty acids was evaluated in plasma by detection of the thiobarbituric acid
      reactive substances (TBARS). Total antioxidant status was measured by
      spectrophotometry. We found a significant increase of elastase, TBARS and NO(x),
      without any significant variation of MPO and TAS. In this group of CRF subjects,
      no statistical correlation was found between these examined parameters,
      creatinine level, creatinine clearance, leukocyte count and hemoglobin level.
      These findings need to be underlined if we consider that chronic renal failure is
      an inflammatory condition and this research furtherly supports literature data
      regarding the role of activated leukocytes in the development of the vascular
      complications. These observations explain why the examination of leukocyte count
      and function could become a tool to verify the clinical outcome in these
      patients.

PMID- 19847060
TI  - Species-specific effects of anticoagulants on red blood cell deformability.

PMID- 19847061
TI  - Aspirin resistance in healthy volunteers.

PMID- 19847062
TI  - Determination of erythrocyte flow velocity by dynamic grey scale measurement
      using off-line image analysis.

PMID- 19847063
TI  - Prostaglandin application improves macro- and microcirculation after aorto-hepato
      mesenteric bypass in chronic mesenteric ischemia.

PMID- 19847064
TI  - Cognitive plasticity and training: key issues at the intersection of behavioral
      and neurophysiological research.

PMID- 19847065
TI  - Cognitive training and plasticity: theoretical perspective and methodological
      consequences.
AB  - PURPOSE: To provide an overview of cognitive plasticity concepts and findings
      from a lifespan developmental perspective. METHODS: After an evaluation of the
      general concept of cognitive plasticity, the most important approaches to study
      behavioral and brain plasticity are reviewed. This includes intervention studies,
      experimental approaches, cognitive trainings, the study of facilitating factors
      for strategy learning and strategy use, practice, and person-environment
      interactions. Transfer and durability of training-induced plasticity is
      discussed. RESULTS: The review indicates that methodological and conceptual
      advances are needed to improve the match between levels of behavioral and brain
      plasticity targeted in current developmental research and study designs.
      CONCLUSIONS: The results suggest that the emphasis of plasticity studies on
      treatment effectiveness needs to be complemented by a strong commitment to the
      grounding of the intervention in a conceptual framework.

PMID- 19847067
TI  - Training of the executive component of working memory: subcortical areas mediate
      transfer effects.
AB  - PURPOSE: Several recent studies show that training can improve working memory
      (WM) performance. In this review, many issues related to WM training, such as
      neural basis, transfer effects, and age-related changes are addressed. METHOD: We
      focus on our own studies investigating training on tasks taxing the executive
      updating function and discuss our findings in relation to results from other
      studies investigating training of the executive component of WM. RESULTS: The
      review confirms positive behavioral effects of training on working memory. The
      most common neural pattern following training is fronto-parietal activity
      decreases. Increases in sub-cortical areas are also frequently reported after
      training, and we suggest that such increases indicate changes in the underlying
      skill following training. Transfer effects are in general difficult to
      demonstrate. Some studies show that older adults increase their performance after
      WM training. However, transfer effects are small or nonexistent in old age.
      CONCLUSIONS: The main finding in this review is that sub-cortical areas seem to
      have a critical role in mediating transfer effects to untrained tasks after at
      least some forms of working memory training (such as updating).

PMID- 19847068
TI  - Measuring compensation and its plasticity across the lifespan.
AB  - PURPOSE: The present paper integrates two important aspects when studying
      compensation: (1) the knowledge about specific compensational mechanisms and (2)
      the consideration of lifelong changes in these mechanisms (i.e., plasticity of
      compensation). Hence, the paper addresses the questions (a) which neural networks
      are supporting successful cognitive performance across development, (b) what are
      the associated compensational mechanisms and (c) are these compensational
      mechanisms plastic across the lifespan. METHODS: To answer these questions, we
      suggest to integrate behavioural and neuroimaging methods and present specific
      methods and their advantages and disadvantages. RESULTS: We will illustrate the
      relevance of this integration by presenting data using ERPs and (s)LORETA to
      study compensational processes across the lifespan in a higher order cognitive
      function, i.e., delayed intentional behaviour. A higher activation in old adults
      or adolescents in successful trials compared to young adults is considered
      compensatory as specialized cortical regions are selectively recruited in
      response to task demands. CONCLUSIONS: Findings show that whereas the performance
      outcome might be the same across age groups, underlying processes and activations
      might be fundamentally different. We conclude with a discussion about specific
      implications of this integrative approach when studying the adaptive potentials
      and limits of human cognition.

PMID- 19847066
TI  - Neuroplasticity and cognitive aging: the scaffolding theory of aging and
      cognition.
AB  - A recent proposal called the Scaffolding Theory of Cognitive Aging (STAC)
      postulates that functional changes with aging are part of a lifespan process of
      compensatory cognitive scaffolding that is an attempt to alleviate the cognitive
      declines associated with aging. Indeed, behavioral studies have shown that aging
      is associated with both decline as well as preservation of selective cognitive
      abilities. Similarly, neuroimaging studies have revealed selective changes in the
      aging brain that reflect neural decline as well as compensatory neural
      recruitment. While aging is associated with reductions in cortical thickness,
      white-matter integrity, dopaminergic activity, and functional engagement in
      posterior brain regions such as the hippocampus and occipital areas, there are
      compensatory increases in frontal functional engagement that correlate with
      better behavioral performance in older adults. In this review, we discuss these
      age-related behavioral and brain findings that support the STAC model of
      cognitive scaffolding and additionally integrate the findings on neuroplasticity
      as a compensatory response in the aging brain. As such, we also examine the
      impact of external experiences in facilitating neuroplasticity in older adults.
      Finally, having laid the foundation for STAC, we briefly describe a proposed
      intervention trial (The Synapse Program) designed to evaluate the behavioral and
      neural impact of engagement in lifestyle activities that facilitates successful
      cognitive scaffolding using a controlled experiment where older adult
      participants are randomly assigned to different conditions of engagement.

PMID- 19847069
TI  - Cognitive plasticity in adulthood and old age: gauging the generality of
      cognitive intervention effects.
AB  - Interventions enabling aging individuals to fulfill their plastic potential
      promise to postpone, attenuate, or even reverse the adverse effects of senescent
      brain changes on cognitive abilities and everyday competence in old age. Based on
      an overview of the concept of plasticity in lifespan development, we selectively
      review evidence from cognitive intervention studies and conclude that most of
      them have failed to observe generalizable performance improvements, as documented
      by the small size and scope of positive transfer to untrained tasks. We further
      note that generally accepted criteria for defining transfer distance are lacking,
      rendering the relevant evidence difficult to interpret. Hence, we propose a
      taxonomy of transfer distance based on the structure of human intellectual
      abilities.

PMID- 19847070
TI  - Far transfer in cognitive training of older adults.
AB  - PURPOSE: This article reviews the literature on far transfer effects in training
      of older adults. METHODS: Adapting a taxonomy of transfer developed by Barnett
      and Ceci (2002), to rehabilitation or enhancement of existing cognitive skills;
      results of studies assessing transfer effects from training of memory, reasoning,
      UFOV, dual task performance, and complex training are classified. RESULTS:
      Comparisons of the transfer outcomes of both strategy training and extended
      practice approaches suggest that far transfer has been observed. CONCLUSIONS:
      Outcomes for strategy studies training memory have had less success than extended
      practice studies in obtaining far transfer. Reasons for this are discussed, as
      are suggestions for improved assessment of transfer outcomes.

PMID- 19847071
TI  - Can we change brain functioning with cognition-focused interventions in
      Alzheimer's disease? The role of functional neuroimaging.
AB  - PURPOSE: This review considers the application of functional magnetic resonance
      imaging (fMRI) to identify treatment effects and brain plasticity in cognition
      focused interventions aimed at people with Alzheimer's disease (AD). At present
      there is little evidence available that bears directly on this question.
      Associative memory function is affected in the early stages of AD and also
      deteriorates disproportionately in comparison to other types of memory in healthy
      ageing. METHODS: We review paradigms from the literature on face-name learning in
      fMRI in three groups (AD, mild cognitive impairment, and healthy ageing) with the
      aim of developing a paradigm to measure treatment effects and functional
      plasticity following cognitive intervention. RESULTS: Previous studies have
      commonly selected participants with high levels of education, and have generally
      used challenging tasks, with considerable variations in level of task performance
      across studies. The findings of the review indicate that there is a need a simple
      face-name learning paradigm that can be used with people with AD, and which can
      be applied either as a single assessment tool to compare various subject groups
      or as an outcome tool to assess functional changes following a period of
      cognitive intervention. CONCLUSIONS: We make recommendations for such a paradigm
      and discuss pilot data showing the successful application of our paradigm in an
      individual with MCI.

PMID- 19847072
TI  - Mesulam's frontal lobe mystery re-examined.
AB  - PURPOSE: Mesulam's (1986) mystery is that some patients with frontal lobe damage
      may show no cognitive impairment according to traditional office-based assessment
      procedures, yet nevertheless show marked cognitive handicap in everyday life.
      Mesulam suggested that "the office setting may introduce sufficient external
      structure to suppress some of these behavioral tendencies" (p. 322). We ask if it
      is indeed the office setting that is the problem, or whether it is that
      traditional assessments do not measure the full range of cognitive functions
      supported by prefrontal cortex. METHOD: Neuropsychological case series study and
      review. RESULTS: Traditional methods for assessing cognitive deficits following
      frontal lobe damage typically do not measure the full range of deficits that can
      occur. In particular, rostral prefrontal cortex supports functions which are not
      routinely assessed yet are crucial to competent everyday life performance. These
      include meta-memory functions (e.g. context and source memory), complex
      behavioural co-ordination (e.g. prospective memory and multitasking), and
      mentalizing. CONCLUSIONS: New clinical assessment procedures are required
      urgently. These could be based, in principle, both on recent experimental
      findings from cognitive neuroscience, and observation of behaviour outside office
      settings. These procedures could then be administered in an office setting.

PMID- 19847073
TI  - Memory training effects in old age as markers of plasticity: a meta-analysis.
AB  - In most studies on plasticity using behavioural data, cognitive plasticity has
      been studied in the context of short-term interventions such as memory training.
      In order to systematically review the literature on memory training and summarize
      its effects for old healthy people and people with mild cognitive impairment on
      multiple functional domains, we conducted a meta-analysis of all published
      randomized controlled trials (RCT) between 1970 and 2007. Overall, 24 studies
      examining memory training effects in healthy and in mildly cognitively impaired
      old adults were identified and included in the analysis. Only memory trainings
      (e.g. memory skills training, imagery, method of loci) with cognitive outcome
      measures, duration of intervention with up to one year with at least a baseline
      and a post-intervention assessment reported, were included. Results demonstrate
      significant training effects for paired associate learning and immediate and
      delayed recall in healthy old adults and for immediate recall in mildly
      cognitively impaired old adults. However, training effects were no larger than
      those found for active control conditions. Our results suggest that evidence on
      the effectiveness and specificity of training interventions is scarce. We discuss
      limitations of existing knowledge about the efficacy of memory training
      interventions and implications for future research to improve knowledge regarding
      effective cognitive interventions.

PMID- 19847074
TI  - The plastic human brain.
AB  - PURPOSE: In this review I summarize and discuss reported findings of structural
      and functional plasticity in the intact human brain. METHODS: The main focus is
      placed on research that uses musicians as a model to study brain plasticity. I
      summarize therefore mostly studies dealing with musicians or with the effect of
      music practice. In the first section, structural plasticity is described on the
      basis of modern neuroanatomical studies using magnetic resonance imaging (MRI)
      techniques. In the second part, emphasis is given to studies reporting functional
      plasticity on the basis of changed neurophysiological activation patterns. These
      studies are discussed in the context of two approaches employed to study
      plasticity in the human brain: the cross-sectional and longitudinal approaches.
      RESULTS: The reviewed studies altogether indicate that experience can shape brain
      anatomy and brain physiology. Brain plasticity as demonstrated here is related to
      changed grey and white mater densities (and volumes) but also to changed
      activation patterns in the brain areas involved in controlling the expertise
      task. CONCLUSIONS: Taken together, all studies support the view that the human
      brain is much more plastic than had been anticipated 20 years ago.

PMID- 19847075
TI  - Flexible and adaptive socio-emotional problem solving in adult development and
      aging.
AB  - PURPOSE: Despite decline in basic cognitive mechanisms, aging adults may also
      possess abilities that allow them to function quite effectively, particularly
      when cognition is examined in a socio-emotional context. In this article, I
      highlight the importance of the functional dynamics or the ability to effectively
      adapt to the demands and opportunities that individuals are confronted with on an
      everyday basis. METHODS: This overview takes into consideration how life
      experiences, social interactions, beliefs, and emotions influence motivational
      goals for processing information in daily life. I present an integrative
      representation of my empirical work and theorizing on the impact of socio
      emotional contextual factors in older adulthood by identifying developmental
      mechanisms and contexts that determine when older adults' everyday problem
      solving and emotion regulation is optimal or adaptive and when it is not.
      RESULTS: Older adults display flexibility in problem solving and emotion
      regulation strategy use as well as a decrease in the amount of resources
      necessary to maintain or regain emotional well-being, while performing well at
      other tasks. CONCLUSIONS: We suggest that growing older has the adaptive
      potential to effectively solve problems, regulate emotions, and reduce the
      cognitive costs of emotion regulation, further corroborating findings of a
      positive and flexible developmental trajectory for emotional control with
      increasing age.

PMID- 19847076
TI  - Cognition and equilibrium regulation in development and aging.
AB  - PURPOSE: Changes in emotion-cognition relationships in later life comprise a
      pattern of both vulnerabilities and strengths. To integrate this pattern of
      diversity, I propose a neo-Piagetian extension of the concepts of equilibrium and
      disequilibrium processes to the relationship beyond cognition to encompass
      emotional activation and arousal, and beyond youth to the full life span.
      CONTENT: Beginning with a simple, Cannon-type equilibrium based on the response
      to increasing deviation from ideal end states of correcting through tension
      reduction, a more complex model is outlined that additionally uses tension
      amplification aimed at enlargement of the range over which stability is
      maintained, i.e., permits processes of developmental progression. Parallel to
      cognitive development, emotional development is described as the emergence of
      more complex cognitive-affective structures out of original automatic,
      biologically based ones. In that process, tension thresholds are raised, and the
      functional range over which equilibrium can be maintained is widened, as higher
      order representations become part of the regulatory network. These progressive
      movements provide well automated emotion regulation whose effectiveness increases
      well into middle and late life. CONCLUSIONS: In contrast to development, aging is
      ultimately characterized by a lowering of tension thresholds similar to
      developmental regression. However, as in the purely intellectual realm, that
      process is offset by the previous automatization and crystallization of cognitive
      affective schemas becomes evident only as a result of increasing constraints on
      fluid capacities, as in advancing age and/or high load of cognitive effort and/or
      emotional activation.

PMID- 19847077
TI  - Is adaptive neuronal plasticity an epiphenomenon of the BOLD-signal?
AB  - PURPOSE: This paper will examine different neurocognitive theories which conclude
      that the brain is able to restore or redress lost or damaged processing systems
      by reorganising remaining neuronal resources. METHOD: The blood oxygenation level
      dependent or BOLD-signal is the most frequently used method for imaging brain
      activity in healthy, young adults, children, the elderly, or subjects with a
      neurodegenerative condition. The BOLD-signal reflects the balance between oxygen
      metabolism and vascular blood supply. The effect of neuronal discharge activity
      and neuronal recruitment on oxygen metabolism and vascular blood supply will be
      described. RESULT: Maturation, senescence or degenerative illness alter the
      balance of oxygen metabolism and vascular blood supply on a regional level. This
      changes the ability to detect brain activity using the BOLD-signal and accounts
      for the activation pattern observed in the young, the old and the ill.
      CONCLUSIONS: The change in activation pattern observed in the young, the old and
      the ill is not the result of a compensatory mechanism but the result of a
      disparity in the neuronal process which can not be compensated for.

PMID- 19847078
TI  - A prospective, randomized clinical trial comparing bipolar plasma kinetic
      resection of the prostate versus conventional monopolar transurethral resection
      of the prostate in the treatment of benign prostatic hyperplasia.
AB  - BACKGROUND AND OBJECTIVE: For treatment of benign prostatic hyperplasia (BPH),
      Plasma Kinetic loop Resection of the Prostate (PKRP) is an alternative to
      conventional monopolar transurethral resection of prostate (TURP). We compared
      outcomes with the two treatments in a randomized trial. PATIENTS AND METHODS:
      Over a one-year period, we randomly assigned patients with an indication for
      surgery for BPH and who met inclusion criteria to treatment with either PKRP or
      TURP. We measured prostate volume by transrectal ultrasound, relief of bladder
      outlet obstruction, operative time, decline in serum sodium and hemoglobin,
      weight of resected prostatic chips, duration of catheterization and hospital
      stay. Patients were evaluated one month after discharge for obstructive symptoms.
      Complications were also recorded. RESULTS: Of 102 patients enrolled, 51 underwent
      PKRP and 51 underwent TURP. Relief of obstructive symptoms and mean operative
      time showed no statistically significant difference. The PKRP group had a smaller
      decline in hemoglobin than the TURP group (0.6 g/dL vs 1.8 g/dL, P=.01), a lower
      reduction in serum sodium levels (1.03 mmol/L vs 5.01 mmol/L, P=.01), a shorter
      catheterization time (37.2 hours versus 57.7 hours, P=.03) and a shorter hospital
      stay (1.5 days versus 2.6 days, P=.02). One patient in the bipolar PKRP group
      needed recatheterization versus four patients in the TURP group. CONCLUSION: PKRP
      reduces morbidity with an outcome similar to conventional monopolar TURP in the
      treatment of BPH.

PMID- 19847079
TI  - Infective endocarditis at a hospital in Saudi Arabia: epidemiology, bacterial
      pathogens and outcome.
AB  - BACKGROUND AND OBJECTIVE: Data on infective endocarditis prevalence, epidemiology
      and etiology from Saudi Arabia and the Gulf region are sparse. We undertook this
      study to describe the pattern and the causative agents of endocarditis at a
      hospital in Saudi Arabia. METHODS: We conducted a retrospective analysis of all
      reported endocarditis cases at the Dhahran Health Center from January 1995 to
      December 2008. RESULTS: Of the 83 cases of endocarditis, 54 (65%) were definite
      endocarditis and the remaining 29 (35%) were possible endocarditis based on the
      Duke criteria. Patients with definite endocarditis included 39 males and 15
      females (ratio of 2.6:1) with a mean age (SD) of 59.7 (18.2) years. Of the
      definite endocarditis cases, native valve endocarditis occurred in 44 (81.5%)
      cases of and prosthetic valve endocarditis was observed in 10 (18.5%). The most
      commonly involved valves were mitral (n=24; 44.4%) and aortic (n=20; 39.2%). The
      most common organisms were S aureus (n=23; 42.6%), Enterococcus faecalis (n=12;
      22.2%) and viridans streptococci (n=9; 16.7%). Surgical intervention was required
      in 17 (31.4%) cases and the in-hospital mortality rate was 29.4% (n=15). Of all
      the patients, 3 (5.5%) had embolic stroke as a complication. CONCLUSION: Native
      valve endocarditis is the predominant type of endocarditis. The patients were
      older adults and the most common organisms were S aureus, E faecalis and viridans
      streptococci.

PMID- 19847080
TI  - Performance of body mass index in predicting diabetes and hypertension in the
      Eastern Province of Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Body mass index (BMI) is the most widely used measure
      to define obesity and predict its complications, such as diabetes and
      hypertension, but its accuracy and usefulness in Saudi subjects is unknown. This
      study aimed to assess the validity of standard BMI cut-point values in the Saudi
      population. SUBJECTS AND METHODS: 197 681 adults participated in a cross
      sectional study to detect diabetes and hypertension in the Saudi Eastern province
      in 2004/2005, with blood pressure, fasting blood sugar, height and weight
      measurements taken. Sensitivities, specificities, areas under the curves,
      predictive values, likelihood ratios, false positive, false negatives and total
      misclassification ratios were calculated for various BMI values determined from
      receiver operating characteristic (ROC) curves. The significance of the
      association between risk factors and BMI was assessed using regression analysis.
      RESULTS: For the definition of overweight, ROC curve analysis suggested optimal
      BMI cut-offs of 28.50 to 29.50 in men and 30.50 to 31.50 in women, but the levels
      of sensitivity and specificity were too low to be of clinical value and the
      overall misclassification was unacceptably high across all the selected BMI
      values (>0.80). The relationship between BMI and the presence of diabetes and/or
      hypertension was not improved when a BMI of 25 was used. Using regression
      analyses, the odds ratios for hypertension and/or diabetes increased
      significantly from BMI values as low as 21-23 with no improvement in the
      diagnostic performance of BMI at these cutoffs. CONCLUSION: In Saudi population,
      there is an increased risk of diabetes and hypertension relative to BMI, starting
      at a BMI as low as 21 but overall there is no cutoff BMI level with high
      predictive value for the development of these chronic diseases, including the WHO
      definition of obesity at BMI of 30.

PMID- 19847081
TI  - Inferior vena caval filters: 5 years of experience in a tertiary care center.
AB  - BACKGROUND AND OBJECTIVES: Interruption of the Inferior Vena Cava (IVC) is
      recommended in certain cases to prevent Pulmonary Embolism (PE). Reported data on
      the efficacy and rate of complications vary considerably. PATIENTS AND METHODS:
      We conducted a retrospective analysis of patients who had a temporary or
      permanent IVC filter inserted at our institution during the past 5 years.
      RESULTS: Seventy-seven of 225 patients (34%) with Venous Thrombosis (VT) had an
      IVC filter inserted. Deep vein thrombosis and PE were the most common causes for
      anticoagulation. Bleeding was the reason for IVC filter insertion in 48 (62%).
      The only complication found was the breaking of a temporary filter during removal
      related to the procedure. However, 3 patients (out of 10) had a recurrence of VT
      after prolonged discontinuation of anticoagulation. CONCLUSIONS: Our criteria for
      indication of IVC filter insertion are in line with current standard of care. The
      immediate and delayed complications caused by IVC filter insertion was low.
      Active bleeding was the most common indication for filter insertion, whereas
      inherited thrombophilia was relatively common.

PMID- 19847082
TI  - Renal biopsy in patients with type 2 diabetes mellitus: indications and nature of
      the lesions.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of non diabetic renal disease (NDRD)
      among patients with type 2 diabetes mellitus varies widely depending on the
      selection criteria and the populations being studied. The aim of this study was
      to evaluate the renal biopsies performed on type 2 diabetic patients for
      suspicion of NDRD and to correlate the pathological with the clinical and
      laboratory findings. SUBJECTS AND METHODS: We selected and reviewed biopsies
      performed on type 2 diabetics for clinically suspected NDRD from January 2006 to
      December 2008 at a single hospital. Clinical and laboratory data were analyzed in
      relation to the histopathology findings. Patients were grouped into either group
      I with isolated DGS or group II with NDRD on top of DGS. RESULTS: Thirty-one
      biopsies were performed on type 2 diabetic patients; Seventeen patients (54.8%)
      were males. Mean age was 50.68 (11.29) years. The mean duration of diabetes was
      9.33 (3.6) years. Renal biopsy showed that among the studied group 14 patients
      (45.2%) showed NDRD on top of DGS. Crescentic glomerulonephritis was the
      commonest finding seen in 3 cases (21.4% of group II cases) followed by acute
      tubulointerstitial nephritis and hypertensive changes each was seen in 2 cases
      (14.4%). Other findings included IgA nephropathy, primary focal segmental
      glomerulosclerosis, rhabdomyolysis, membranoproliferative glomerulonephritis each
      of them was seen in one case (7.1%). Group I had a significantly higher level of
      proteinuria 4.97 (2.08) gm/24 hrs urine than group II 2.72 (1.09) gm/24 hrs urine
      (P=.003). There was no significant difference between the two groups in age,
      duration of diabetes, gender, presence of hypertension, hematuria, serum
      creatinine or glomerular filtration rate. CONCLUSION: The present study showed
      that crescentic glomerulonephritis is the commonest NDRD among diabetic patients.
      A higher level of proteinuria was reported among those with NDRD superimposed on
      DGS. So, Renal biopsy should be performed in diabetics when the clinical scenario
      is atypical.

PMID- 19847083
TI  - Clinical characteristics and computed tomography findings in Arab patients
      diagnosed with pulmonary sarcoidosis.
AB  - BACKGROUND AND OBJECTIVE: Sarcoidosis is prevalent worldwide with significant
      heterogeneity across different ethnic groups. We aimed To describe the clinical
      characteristics and computed tomography findings among Arab patients with
      pulmonary sarcoidosis. METHODS: A retrospective study of patient demographics,
      symptoms, co-morbid illness, sarcoidosis stage, treatment, pulmonary function and
      CT results. RESULTS: Of 104 patients, most (77%) were 40 years of age or older at
      diagnosis, and females in this category (40 years ) significantly outnumbered
      male patients (69/104 (66.3%) vs. 35/104 (33.7%), P=.003). The most common
      complaints were dyspnea (76%), cough (72.1%) and weight loss (32.7%). The
      majority of patients displayed impairment in lung function parameters at
      presentation. However, significant impairment in forced vital capacity,
      percentage predicted (FVC%) ( CONCLUSION: At presentation, clinical
      manifestations of sarcoidosis among this sample of Arab patients were similar to
      reports from other nations. Further studies are needed to explore the effects of
      race and ethnicity on disease severity in the Middle East.

PMID- 19847084
TI  - Management of end-stage heart failure: a perspective on the Arab Gulf states.
AB  - The ever expanding epidemic of end-stage heart failure represents one of the
      greatest challenges of modern cardiovascular medicine. With medical treatments
      hampered by significant limitations, physicians caring for patients with advanced
      heart disease have turned to cardiac transplantation and durable mechanical
      circulatory assist devices as definitive therapies. These advanced therapeutic
      modalities are not widely available outside the United States and Europe, but
      nevertheless offer enormous potential for patients in the Arab Gulf suffering
      from end-stage heart failure. This review will discuss the management of end
      stage heart failure in the Gulf States, with an emphasis on therapies best
      utilized within a framework of regional cooperation and coordination.

PMID- 19847085
TI  - The prevalence and diagnostic performance of anti-cyclic citrullinated peptide
      antibody in rheumatoid arthritis: the predictive and discriminative ability of
      serum antibody level in recognizing rheumatoid arthritis.
AB  - BACKGROUND AND OBJECTIVES: The utility of anticyclic citrullinated peptide (anti
      CCP) antibody in the diagnosis of rheumatoid arthritis (RA) varies across
      different studies. We determined the diagnostic performance and predictive
      ability of anti-CCP for RA. METHODS: We studied 201 patients with RA and compared
      them with 208 non-RA patients as controls. RA patients included in the study
      fulfilled the American College of Rheumatology revised criteria and patients with
      other diseases as well as those with undifferentiated arthritis (UIA) were used
      as controls. Anti-CCP was measured by enzyme-linked immunosorbent assay (ELISA)
      and rheumatoid factor (RF) by the agglutination method. The optimal cutoff value
      and diagnostic accuracy were determined using receiver operating characteristics
      (ROC) curve and area under the curve (AUC).The sensitivity and specificity were
      determined by comparison of RA patients with non-RA controls. RESULTS: The anti
      CCP test was positive in 164 patients with RA for a sensitivity of 81.6%,
      specificity of 87.5%, and overall accuracy of 84.6%. The respective values for RF
      were 75.6%, 86.5% and 84.4%. The anti-CCP test discriminated RA from non-RA
      patients with high accuracy (AUC=0.889 [0.017] 95% CI, 0.856-0.952, P=.001), and
      predicted progression of UIA to RA with moderate accuracy (AUC=0.733 [0.069], 95%
      CI 0.60-0.87, P<.006) at a sensitivity of 75% and a specificity of 68.1%. Among
      60 UIA patients, in 16 (26.7%) who differentiated to RA, the mean (standard
      deviation) for anti-CPP was significantly higher than in 24 (40%) patients who
      progressed to non-RA (134.8 [172] vs 46 [86] U/mL, P<.01). CONCLUSION: These
      findings indicate that anti-CCP yields higher sensitivity and overall accuracy,
      but slightly greater specificity than RF for diagnosis of RA. Anti-CCP
      positivity, particularly a higher level of serum antibody in patients with UIA,
      may be a predictor of subsequent RA.

PMID- 19847086
TI  - Diffuse idiopathic hyperplasia of the sternocleidomastoid muscle in a child.
AB  - Unilateral diffuse or localized enlargement of the sternocleidomastoid muscle
      (SCM) is an event commonly seen in infancy, and is popularly known as
      'sternocleidomastoid tumor'. The condition, which usually spontaneously resolves
      with or without physiotherapy, is due to a hematoma following a difficult labor.
      The muscle regains its elasticity and complete function. In some infants it
      resolves with fibromatous changes in the muscle leading to shortening, fibrosis
      and finally culminating in torticollis. We describe a case of idiopathic diffuse
      enlargement of unilateral SCM in a 12-year-old child without any functional
      compromise or torticollis. The histopathological and clinical characteristics
      differentiating it from more commonly described sternocleidomastoid tumor or
      fibromatosis coli are described. We believe this is the first case report of
      idiopathic hyperplasia of SCM.

PMID- 19847087
TI  - Hepatic vasculitis mimicking liver abscesses in a patient with systemic lupus
      erythematosus.
AB  - Clinical and radiological liver diseases are uncommon in patients with systemic
      lupus erythematosus (SLE). We report a 29-year-old female with SLE who presented
      with right upper quadrant abdominal pain, thrombocytopenia, elevated liver
      enzymes and multiple hypodense lesions in the liver on a computed tomography (CT)
      study that mimicked multiple liver abscesses. A liver biopsy showed mild chronic
      inflammation. Culture results were negative. With steroid therapy the patient
      improved clinically, the platelet count returned to the normal range and the
      multiple liver lesions disappeared radiologicaly. This patient represents a rare
      case of SLE that had hepatic vasculitis mimicking multiple liver abscesses.

PMID- 19847088
TI  - Lymphoepithelioma-like carcinoma of the urinary bladder: report of a rare case.
AB  - Lymphoepithelioma-like carcinoma (LELC) is a rare malignant neoplasm in the
      urinary bladder, which can histologically mimic lymphoma, poorly differentiated
      invasive transitional cell carcinoma or poorly differentiated squamous cell
      carcinoma with a lymphoplasmacytic background. A urinary bladder tumor was
      identified in a 65-year-old man suffering from hematuria for several weeks.
      Transurethral biopsy revealed an undifferentiated tumor with prominent
      lymphocytes and plasma cell infiltration. Immunohistochemical evaluation showed
      positive staining for cytokeratin and epithelial membrane antigen. Subsequent
      radical cystectomy showed pure LELC. We present the case to highlight the
      significance of recognizing this unusual bladder tumor and discuss the important
      differential diagnosis, treatment options and prognosis.

PMID- 19847089
TI  - Poland-Mobius syndrome in an infant girl.
AB  - Mobius syndrome is a rare condition of unclear origin, characterized by a
      unilateral or bilateral congenital facial weakness with impairment of ocular
      abduction, which is frequently associated with limb anomalies . Poland described
      a condition in which there was unilateral absence of pectoralis major muscle and
      ipsilateral syndactyly. The combination of Poland-Mobius syndrome is rare, with
      an estimated prevalence 1:500 000. We describe a case of Poland-Mobius syndrome
      in association with congenital bilateral vocal fold immobility. To our knowldge,
      this is the first report of such an association between Poland-Mobius syndrome
      and congenital bilateral vocal fold immobility.

PMID- 19847090
TI  - Uncommon osseous involvement in multisystemic sarcoidosis.

PMID- 19847092
TI  - Management of food allergy in Japan "food allergy management guideline 2008
      (revision from 2005)" and "guidelines for the treatment of allergic diseases in
      schools".
AB  - In 2005, the "Food Allergy Management Guideline 2005" was published. In order to
      encompass food allergy from infancy to adulthood, the project committee included
      not only pediatricians, but also internists, dermatologists, and
      otolaryngologists. After the release of the guideline, oral food challenge tests
      were approved as a medical examination on hospital admission by the national
      health insurance system in 2006, and the tests at outpatient clinics were also
      approved in 2008. As clearly stated in the guideline, it is essential for general
      practitioners to refer food allergy patients to specialists to receive accurate
      diagnosis. A specialist is needed because the oral food challenge test, which is
      sometimes required for accurate diagnosis, carries the potential risk of
      developing an adverse reaction. In 2008, the "Food Allergy Management Guideline
      2008" was revised to update recent advances, such as the appropriate conditions
      needed to perform oral food challenge tests and probability curves for hen's egg
      and cow's milk developed in Japan. In the same year, "The Guidelines for the
      Treatment of Allergic Diseases in Schools" was published by the Japanese Society
      of School Health. In addition to the guideline, "School Life Management
      Certificate (for Allergic Diseases) " was developed in order to allow the
      verification of the diagnosis and encourage the discussion of countermeasures by
      parents/guardians and school teachers for students requiring special care. It is
      hoped that this review article will be useful for doctors treating food allergy
      and that the quality of life of food allergy patients and their parents will be
      improved.

PMID- 19847091
TI  - Growth parameters and calcium homeostasis in cystic fibrosis patients with CFTR
      I1234V mutation.

PMID- 19847093
TI  - Diagnosis of food allergy based on oral food challenge test.
AB  - Diagnosis of food allergy should be based on the observation of allergic symptoms
      after intake of the suspected food. The oral food challenge test (OFC) is the
      most reliable clinical procedure for diagnosing food allergy. The OFC is also
      applied for the diagnosis of tolerance of food allergy. The Japanese Society of
      Pediatric Allergy and Clinical Immunology issued the 'Japanese Pediatric
      Guideline for Oral Food Challenge Test in Food Allergy 2009' in April 2009, to
      provide information on a safe and standardized method for administering the OFC.
      This review focuses on the clinical applications and procedure for the OFC, based
      on the Japanese OFC guideline.

PMID- 19847094
TI  - Food allergy: review, classification and diagnosis.
AB  - Food allergies, defined as an immune response to food proteins, affect as many as
      8% of young children and 2% of adults in westernized countries, and their
      prevalence appears to be rising like all allergic diseases. In addition to well
      recognized urticaria and anaphylaxis triggered by IgE antibody-mediated immune
      responses, there is an increasing recognition of cell-mediated disorders such as
      eosinophilic esophagitis and food protein-induced enterocolitis. New knowledge is
      being developed on the pathogenesis of both IgE and non-IgE mediated disease.
      Currently, management of food allergies consists of educating the patient to
      avoid ingesting the responsible allergen and initiating therapy if ingestion
      occurs. However, novel strategies are being studied, including sublingual/oral
      immunotherapy and others with a hope for future.

PMID- 19847095
TI  - Oral allergy syndrome.
AB  - Oral allergy syndrome (OAS) is defined as the symptoms of IgE-mediated immediate
      allergy localized in the oral mucosa, and the characteristics depend on the
      lability of the antigen. Another term used for this syndrome is pollen-food
      allergy (PFS); the patient is sensitized with pollen via the airways and exhibits
      an allergic reaction to food antigen with a structural similarity to the pollen
      (class 2 food allergy). In addition to PFS, latex-fruit syndrome is also well
      known as the disease exhibiting OAS. In treating the condition, it must be noted
      that most but not all symptoms of PFS are those of OAS. In many cases, antigens
      become edible by heating, but some are resistant to heating. Also, since the
      exacerbation of atopic dermatitis is occasionally observed after the intake of
      cooked antigens in asymptomatic individuals, careful inquiry of the history is
      important in designing the treatment. Immunotherapy against the cross-reacting
      pollen has also been attempted in PFS.

PMID- 19847096
TI  - Food-dependent exercise-induced anaphylaxis -importance of omega-5 gliadin and
      HMW-glutenin as causative antigens for wheat-dependent exercise-induced
      anaphylaxis-.
AB  - Food-dependent exercise-induced anaphylaxis (FDEIA) is a special form of food
      allergy where a food-intake alone does not induce any symptoms. However, allergic
      symptoms are elicited when triggering factors such as exercise or aspirin-intake
      are added after ingestion of the causative food. The most frequent causative
      foodstuff in Japan is wheat. The triggering factors, both exercise and aspirin
      intake, facilitate allergen absorption from the gastrointestinal tract, resulting
      in allergic symptoms in the patients with wheat-dependent exercise-induced
      anaphylaxis (WDEIA). Analysis using purified wheat proteins revealed that
      approximately 80% of the patients with WDEIA have IgE reacting to omega-5 gliadin
      and the remaining of the patients to high molecular weight glutenin (HMW
      glutenin). Simultaneous measurement of specific IgE to omega-5 gliadin and HMW
      glutenin was found to be highly useful in diagnosing WDEIA compared with the
      routine diagnostic system for wheat.

PMID- 19847097
TI  - Ozone and nitric oxide interaction in Arabidopsis thaliana: a role for ethylene?
AB  - Nitric oxide (NO) is involved together with reactive oxygen species (ROS) in the
      activation of various stress responses in plants. However, the biochemical
      mechanisms by which ROS and NO participate, and the potential interaction between
      these molecules are still unclear. Ozone (O(3)) can be used as a tool to elicit
      ROS-activated stress responses and to activate cell death in plant leaves. We
      have recently shown that O(3) induced a rapid accumulation of NO in Arabidopsis
      leaves and at late time points NO production coincided with the formation of
      hypersensitive response like lesions. Experiments using O(3) and the NO-donor SNP
      alone or in combination indicated that both molecules are capable of activating a
      large set of stress related genes. In combined treatment, NO attenuated O(3)
      induction of salicylic acid (SA) biosynthetic and signaling genes, and reduced SA
      accumulation. In addition, NO can elevate the levels of ethylene in several
      mutants. Thus, NO is a modifier of ROS signaling.

PMID- 19847098
TI  - Identification of cytoskeleton-associated genes expressed during Arabidopsis
      syncytial endosperm development.
AB  - During the early stages of Arabidopsis seed development, the endosperm is
      syncytial and proliferates rapidly through multiple rounds of mitosis in the
      absence of cytokinesis and cell wall formation. This stage of endosperm
      development is important in determining seed viability and size. To identify
      genes involved in syncytial endosperm development, we analyzed the endosperm
      transcriptome, obtained using laser capture microdissection of developing seeds
      at four days after pollination. Our results support the idea that similar sets of
      genes are required for conventional somatic mitosis with cytokinesis and
      syncytial proliferation. Furthermore, we identify cytoskeleton associated genes
      that may act to facilitate syncytial development thereby providing an important
      resource for further characterization of the processes involved in syncytial
      endosperm development.

PMID- 19847099
TI  - Loss of autumn colors under domestication: a byproduct of selection for fruit
      flavor?
AB  - According to the coevolution hypothesis the red autumn leaves of certain tree
      species are a warning signal towards insects that lay their eggs on the trees. A
      recent study has shown that red leaves are common in wild varieties of apple
      (Malus pumila) but not in cultivated varieties. This suggests that autumn colors
      have been lost during domestication due to relaxed selection against insects. The
      few varieties with red leaves have small fruits, similar to their wild ancestors,
      which shows that they have been under less effective artificial selection. As
      expected by the coevolution hypothesis these red varieties are very susceptible
      to an insectborne disease, fire blight. Here I report further data on the loss of
      autumn colors under domestication. Since red leaf color is correlated with red
      fruit flesh color, if red fruit flesh has more astringent taste it is possible
      that loss of autumn colors is not only due to relaxed selection against insect,
      but also to direct artificial selection against astringent taste. However even
      varieties with yellow flesh turn out to have astringent taste. Moreover, while
      red fruit flesh is common in cultivated varieties with red leaves, it is very
      rare in wild varieties. It is unclear, therefore, whether loss of autumn color
      under domestication was a byproduct of artificial selection against red fruit
      flesh.

PMID- 19847101
TI  - Maize black Mexican sweet suspension cultured cells are a convenient tool for
      studying aquaporin activity and regulation.
AB  - Aquaporins (AQPs) are channel proteins that facilitate and regulate the
      permeation of water across biological membranes. Black Mexican sweet suspension
      cultured cells are a convenient model for studying the regulation of maize AQP
      expression and activity. Among other advantages, a single cell system allows the
      contribution of plasma membrane AQPs (PIPs, plasma membrane intrinsic proteins)
      to the membrane water permeability coefficient (P(f)) to be determined using
      biophysical measurement methods, such as the cell pressure probe or protoplast
      swelling assay. We generated a transgenic cell culture line expressing a tagged
      version of ZmPIP2;6 and used this material to demonstrate that the ZmPIP2;6 and
      ZmPIP2;1 isoforms physically interact. This kind of interaction could be an
      additional mechanism for regulating membrane water permeability by acting on the
      activity and/or trafficking of PIP hetero-oligomers.

PMID- 19847100
TI  - Calcium regulation in endosymbiotic organelles of plants.
AB  - In plant cells calcium-dependent signaling pathways are involved in a large array
      of biological processes in response to hormones, biotic/abiotic stress signals
      and a variety of developmental cues. This is generally achieved through binding
      of calcium to diverse calcium-sensing proteins, which subsequently control
      downstream events by activating or inhibiting biochemical reactions. Regulation
      by calcium is considered as a eukaryotic trait and has not been described for
      prokaryotes. Nevertheless, there is increasing evidence indicating that
      organelles of prokaryotic origin, such as chloroplasts and mitochondria, are
      integrated into the calcium-signaling network of the cell. An important
      transducer of calcium in these organelles appears to be calmodulin. In this
      review we want to give an overview over present data showing that endosymbiotic
      organelles harbour calcium-dependent biological processes with a focus on
      calmodulin-regulation.

PMID- 19847102
TI  - Floral organ size control: interplay between organ identity, developmental
      compartments and compensation mechanisms.
AB  - Growth of lateral organs is a complex mechanism that starts with formation of
      lateral primordia. Basal developmental programs like polarity, organ identity and
      environmental cues influence the final organ size achieved via coordinated cell
      division and expansion. Recent evidence shows that the precise balance between
      these two processes, known as compensation mechanisms, seems to be influenced by
      the identity of the organ. Furthermore, studies of mutants affected in floral
      organ size suggest the existence of developmental compartments within different
      floral whorls that show distinct compensation behaviors.

PMID- 19847103
TI  - Amino acid changes during sunflower infection by the necrotrophic fungus B.
      cinerea.
AB  - Metabolic changes that occur in host tissues during a necrotrophic plant/fungal
      interaction have been poorly investigated. Whereas carbon metabolism
      reprogramming and photosynthesis disturbances have been studied, data on plant
      amino acids stores during infection are scarce. Here we report an analysis of
      sunflower cotyledon amino acid content during infection with the necrotrophic
      fungus Botrytis cinerea, by using (13)C-NMR spectroscopy. A rapid disappearance
      of plant amino acids was observed, most probably due to fungal assimilation. In
      order to explore amino acid changes due to host reaction, we investigated the
      amino acid content in healthy and invaded region of infected leaves. During the
      course of infection, glutamate store was affected at distance in the non invaded
      region. Glutamate depletion was correlated to an enhanced sunflower glutamate
      dehydrogenase (GDH) transcription level in the area invaded by pathogen. Our data
      suggest that glutamate could be transferred to the invaded region to supply
      nitrogen. Such a strategy could delay cell death, and consequently disturb fungal
      progression in plant tissues.

PMID- 19847104
TI  - Role of auxin-responsive genes in biotic stress responses.
AB  - Although the phytohormone auxin has been implicated primarily in developmental
      processes, some recent studies suggest its involvement in stress/defense
      responses as well. Recently, we identified auxin-responsive genes and reported
      their comprehensive transcript profiling during various stages of development and
      abiotic stress responses in crop plant rice. The analysis revealed tissue
      specific and overlapping expression profiles of auxin-responsive genes during
      various stages of reproductive development. In addition, a large number of auxin
      responsive genes were also found to be differentially expressed under various
      abiotic stress conditions. Here, we further analyze the expression profiles of
      auxin-responsive genes during various biotic stress conditions. Several auxin
      responsive genes showed response to biotic stress as well. Our analysis provides
      evidence for role of auxin in plant defense responses and suggests cross-talk
      between auxin, abiotic stress and biotic stress signaling pathways.

PMID- 19847105
TI  - Nectar chemistry is tailored for both attraction of mutualists and protection
      from exploiters.
AB  - Plants produce nectar to attract pollinators in the case of floral nectar (FN)
      and defenders in the case of extrafloral nectar (EFN). Whereas nectars must
      function in the context of plant-animal mutualisms, their chemical composition
      makes them also attractive for non-mutualistic, exploiting organisms: nectar
      robbers and nectar-infesting microorganisms. We reviewed the chemical composition
      of both FNs and EFNs and found that nectar composition appears tailored to fulfil
      these ambivalent roles. Carbohydrates and amino acids usually function in the
      attraction of mutualists and appear adapted to the physiological needs of the
      respective mutualists. Volatiles are a further group of compounds that serves in
      the attractive function of nectars. By contrast, secondary compounds such as
      alkaloids and phenols serve the protection from nectar robbers, and most nectar
      proteins that have been characterised to date protect FN and EFN from microbial
      infestation. Nectar components serve both in attraction and the protection of
      nectar.

PMID- 19847106
TI  - Genetic analysis of ethylene regulation of legume nodulation.
AB  - The gaseous hormone ethylene has multiple roles in plant development and
      responses to external cues. Among these is the regulation of "Rhizobium"-induced
      nodulation in legumes. Extensive descriptive literature exists, but has been
      expanded to allow more mechanistic analysis through the application of genetics.
      Both mutants and transgenics displaying ethylene insensitivity have now been
      described, suggesting an intimate interplay of ethylene response, plant
      development and nodulation.

PMID- 19847107
TI  - Role of glucose in spatial distribution of auxin regulated genes.
AB  - Plants have the ability to adjust its physiology and metabolism to the changes of
      nutrient availability in the environment. Since a number of common responses are
      regulated by sugar and auxin, the obvious question arises is whether sugar and
      auxin act interdependently to bring about changes in plant morphology. In the
      February issue of the PLoS ONE, we presented detailed investigation of glucose
      and auxin signaling interaction in controlling root growth and development in
      Arabidopsis thaliana seedlings. Further analysis of tissue specific regulation of
      glucose auxin signaling interaction may provide some insight as to how these two
      signaling molecules interact to control the morphogenic changes during seedling
      development.

PMID- 19847108
TI  - Induced plant volatiles allow sensitive monitoring of plant health status in
      greenhouses.
AB  - A novel approach to support the inspection of greenhouse crops is based on the
      measurement of volatile organic compounds emitted by unhealthy plants. This
      approach has attracted some serious interest over the last decade. In pursuit of
      this interest, we performed several experiments at the laboratory-scale to
      pinpoint marker volatiles that can be used to indicate certain health problems.
      In addition to these laboratory experiments, pilot and model studies were
      performed in order to verify the validity of these marker volatiles under real
      world conditions. This paper provides an overview of results and gives an outlook
      on the use of plant volatiles for plant health monitoring.

PMID- 19847109
TI  - Potential sources of nitrogen in an ant-garden tank-bromeliad.
AB  - Epiphytic plants in general and bromeliads in particular live in a water and
      nutrient-stressed environment often limited in nitrogen. Thus, these plants have
      developed different ways to survive in such an environment. We focused on Aechmea
      mertensii (Bromeliaceae), which is both a tank-bromeliad and an ant-garden (AG)
      epiphyte initiated by either the ants Camponotus femoratus or Pachycondyla
      goeldii. By combining a study of plant morphology and physiology associated with
      aquatic insect biology, we demonstrate that the ant species influences the leaf
      structure of the bromeliad, the structure of the aquatic community in its tank,
      and nutrient assimilation by the leaves. Based on nitrogen and nitrogen stable
      isotope measurements of the A. mertensii leaves, the leaf litter inside of the
      tank and the root-embedded carton nest, we discuss the potential sources of
      available nitrogen for the plant based on the ant partner. We demonstrate the
      existence of a complex ant-plant interaction that subsequently affects the
      biodiversity of a broader range of organisms that are themselves likely to
      influence nutrient assimilation by the A. mertensii leaves in a kind of plant
      invertebrate-plant feedback loop.

PMID- 19847110
TI  - Unripe red fruits may be aposematic.
AB  - The unripe fruits of certain species are red. Some of these species disperse
      their seeds by wind (Nerium oleander, Anabasis articulata), others by adhering to
      animals with their spines (Emex spinosa) or prickles (Hedysarum spinosissimum).
      Certainly neither type uses red coloration as advertisement to attract the seed
      dispersing agents. Fleshy-fruited species (Rhamnus alaternus, Rubus sanguineus
      and Pistacia sp.), which disperse their seeds via frugivores, change fruit color
      from green to red while still unripe and then to black or dark blue upon
      ripening. The red color does not seem to function primarily in dispersal (unless
      red fruits form advertisement flags when there are already black ripe fruits on
      the plant) because the red unripe fruits of these species are poisonous, spiny,
      or unpalatable. The unripe red fruits of Nerium oleander are very poisonous,
      those of Rhamnus alaternus and Anabasis articulata are moderately poisonous,
      those of Rubus sanguineus are very sour, those of Pistacia sp. contain
      unpalatable resin and those of Emex spinosa and Hedysarum spinosissimum are
      prickly. We propose that these unripe red fruits are aposematic, protecting them
      from herbivory before seed maturation.

PMID- 19847111
TI  - Rapid accumulation of NO regulates ABA catabolism and seed dormancy during
      imbibition in Arabidopsis.
AB  - Nitric oxide's (NO) involvement in breaking seed dormancy has been demonstrated
      in previous research but its action mechanism remains to be clarified. We
      observed that a rapid accumulation of NO induces an equally rapid decrease of
      abscisic acid (ABA) that is required for the NO's action in Arabidopsis. In
      addition, the NO-induced ABA decrease correlates with the regulation of CYP707A2
      transcription and the (+)-abscisic acid 8'-hydroxylase (encoded by CYP707A2)
      protein expression. By analyzing cyp707a1, cyp707a2 and cyp707a3 mutants, we
      found that CYP707A2 plays a major role in ABA catabolism during the first stage
      of imbibition. Fluorescent images demonstrate that NO is released rapidly in the
      early hours at the endosperm layer during imbibition. Evidently such response
      precedes the enhancement of ABA catabolism which is required for subsequent seed
      germination.

PMID- 19847112
TI  - Intracellular Ca2+ stores could participate to abscisic acid-induced
      depolarization and stomatal closure in Arabidopsis thaliana.
AB  - In Arabidopsis thaliana cell suspension, abscisic acid (ABA) induces changes in
      cytosolic calcium concentration ([Ca(2+)](cyt)) which are the trigger for ABA
      induced plasma membrane anion current activation, H(+)-ATPase inhibition, and
      subsequent plasma membrane depolarization. In the present study, we took
      advantage of this model to analyze the implication of intracellular Ca(2+) stores
      in ABA signal transduction through electrophysiological current measurements,
      cytosolic Ca(2+) activity measurements with the apoaequorin Ca(2+) reporter
      protein and external pH measurement. Intracellular Ca(2+) stores involvement was
      determined by using specific inhibitors of CICR channels: the cADP
      ribose/ryanodine receptor (Br-cADPR and dantrolene) and of the inositol
      trisphosphate receptor (U73122). In addition experiments were performed on
      epidermal strips of A. thaliana leaves to monitor stomatal closure in response to
      ABA in presence of the same pharmacology. Our data provide evidence that
      ryanodine receptor and inositol trisphosphate receptor could be involved in ABA
      induced (1) Ca(2+) release in the cytosol, (2) anion channel activation and H(+)
      ATPase inhibition leading to plasma membrane depolarization and (3) stomatal
      closure. Intracellular Ca(2+) release could thus contribute to the control of
      early events in the ABA signal transduction pathway in A. thaliana.

PMID- 19847113
TI  - Circadian oscillation of starch branching enzyme gene expression in the sorghum
      endosperm.
AB  - Expression of the three SBE genes, encoding starch branching enzymes, in the
      sorghum endosperm exhibited a diurnal rhythm during a 24-h cycle. Remarkably, the
      oscillation in SBE expression was maintained in cultured spikes after a 48-h dark
      treatment, also when fed a continuous solution of sucrose or abscisic acid. Our
      findings suggest that the rhythmicity in SBE expression in the endosperm is
      independent of cues from the photosynthetic source and that the oscillator
      resides within the endosperm itself.

PMID- 19847114
TI  - Reverse genetics and transient gene expression in fleshy fruits: overcoming plant
      stable transformation.
AB  - Fast methods to validate relevant candidate genes associated to fruit ripening
      are needed specially to associate gene function to the overwhelming amount of
      leads provided by genomic projects. In tomato, the use of Fruit VIGS in a
      Del/Ros1 background as described in the Plant Physiology by Orzaez et al. 2009,
      overcomes the difficulties associated to low efficiency VIGS in tomato and
      increases the reliability and throughput of this fast reverse genetic assay. The
      advantages of this transient assay system are discussed here for the case of gene
      functions associated to fruit ripening and quality traits. The possibility of
      using other reporters or even the development of transient overexpression assays
      in the fruit is also discussed.

PMID- 19847115
TI  - Zinc transport mediated by barley ZIP proteins are induced by low pH.
AB  - It is estimated that nearly 50% of the world's population is at risk of zinc (Zn)
      deficiency. The challenge is therefore to increase the Zn content in edible plant
      parts in order to improve the nutritional value of staple foods. We recently
      reported the identification and characterization of three barley genes encoding
      zinc transport proteins belonging to the ZIP protein family. These proteins are
      believed to be involved in cellular uptake of Zn(2+). In this addendum, the
      Zn(2+) transport capacity of ZIP proteins isolated from barley roots was
      investigated in response to various pH levels. We show that a lowering of pH
      induces a better growth at low Zn(2+) concentrations of yeast cells expressing
      ZIP proteins. However, no significant change in transport capacity (V(max)) could
      be observed for HvIRT1, whereas lowering of pH from 5.5 to 4.2 increased the
      V(max) value with 64% for HvZIP5. These results indicate that proton activity has
      an important role in regulating the Zn(2+) transport capacity of Zn(2+) specific
      ZIP transport proteins. This information will increase the understanding of ZIP
      proteins and facilitate engineering of genotypes able to grow efficiently on
      marginal soils.

PMID- 19847116
TI  - Analysis of the arabidopsis dry2/sqe1-5 mutant suggests a role for sterols in
      signaling.
AB  - Sterols play multi-faceted roles in all eukaryotes. In plants, there are mounting
      evidences pointing to sterols, other than BRs, can act as signaling molecules.
      The Arabidopsis dry2/sqe1-5 mutant has multiple developmental defects caused by a
      point mutation in the SQE1 gene that generates a hypomorphic allele. SQE1 encodes
      a squalene epoxidase, which converts squalene into 2,3-oxidosqualene the
      precursor of plant sterols. Genetic, molecular and biochemical analyses suggest
      that dry2/sqe1-5 defective phenotypes cannot be simply explained by a depletion
      of bulk sterols but rather by altered ROS. It remains to be elucidated whether
      the altered ROS production of the mutant is caused by membrane composition, which
      in turn affect the lipid rafts composition and/or an altered signaling.

PMID- 19847117
TI  - Biomechanics of climbing palms and how they climb.
AB  - Climbing plants have fascinated botanists since the pioneering works of Darwin
      and his contemporaries in the 19(th) century. Diverse plants have evolved
      different ways of climbing and a wide range of attachment devices and stem
      biomechanics to cope with the particular physical demands of life as a climber.
      We investigated the biomechanics of attachment in a range of climbing palms,
      including true rattans from Southeast Asia and the genus Desmoncus from South
      America. We found that hook strength and orientation is coordinated with rachis
      geometry and rigidity. These findings support the notion of a ratchet-type
      attachment mechanism and partly explain why these spiny plants are so catchy and
      efficient at attaching to supports.

PMID- 19847118
TI  - Oxidation of hydroxylamines to NO by plant cells.
AB  - At least theoretically, plants may synthesize nitric oxide (NO) either by
      reduction of N in higher oxidations states, or by oxidation of more reduced N
      compounds. The well established reductive pathway uses nitrite as a substrate,
      produced by cytosolic nitrate reductase. The only oxidative pathway described so
      far comprises nitric oxide synthase (NOS)-like activity, where guanidino-N from L
      arginine is oxidized to NO. In our previous paper we have demonstrated yet
      another form of oxidative NO formation, whereby hydroxylamine (HA), but also the
      AOX-inhibitor salicylhydroxamate (SHAM) is oxidized to NO by tobacco suspension
      cells. Oxidation of HA to NO was also demonstrated in vitro by using ROS
      producing enzymes. Apparently superoxide radicals and/or hydrogen peroxide served
      as oxidants. Another unexpected observation pointed to a special role for
      superoxide dismutase in oxidative NO formation.

PMID- 19847119
TI  - Role of PP2C-mediated ABA signaling in the moss Physcomitrella patens.
AB  - Plant hormone abscisic acid (ABA) is found in a wide range of land plants, from
      mosses to angiosperms. However, our knowledge concerning the function of ABA is
      limited to some angiosperm plant species. We have shown that the basal land plant
      Physcomitrella patens and the model plant Arabidopsis thaliana share a conserved
      abscisic acid (ABA) signaling pathway mediated through ABI1-related type 2C
      protein phosphatases (PP2Cs). Ectopic expression of Arabidopsis abi1-1, a
      dominant allele of ABI1 that functions as a negative regulator of ABA signaling,
      or targeted disruption of Physcomitrella ABI1-related gene (PpABI1A) resulted in
      altered ABA sensitivity and abiotic stress tolerance of Physcomitrella, as
      demonstrated by osmostress and freezing stress. Moreover, transgenic
      Physcomitrella overexpressing abi1-1 showed altered morphogenesis. These
      transgenic plants had longer stem lengths compared to the wild type, and
      continuous growth of archegonia (female organ) with few sporophytes under non
      stress conditions. Our results suggest that PP2C-mediated ABA signaling is
      involved in both the abiotic stress responses and developmental regulation of
      Physcomitrella.

PMID- 19847120
TI  - Novel aspects of COP9 signalosome functions revealed through analysis of
      hypomorphic csn mutants.
AB  - The COP9 signalosome (CSN) is a conserved eukaryotic protein complex implicated
      in the regulation of cullin-RING type E3 ubiquitin ligases by cleaving the small
      peptide RUB/Nedd8 from cullins. However, detailed analysis of CSN physiological
      functions in Arabidopsis has been hampered by the early seedling-lethality of csn
      null mutants. We and others have now identified a number of viable hypomorphic
      csn mutants which start to reveal novel CSN-dependent activities in adult
      Arabidopsis plants. Here, we present a detailed comparative analysis of the csn5a
      1 and csn2-5 mutants as a mean to improve understanding of CSN functions in plant
      cells. Our observations point to CSN-independent activities of CSN5 and suggest a
      role of the CSN in cytoskeleton assembly/organization.

PMID- 19847121
TI  - A possible mechanism for the apocynin-induced nitric oxide accumulation in
      plants.
AB  - Nitric oxide (NO) is a small, ubiquitous bioactive molecule, postulated as a
      broad spectrum anti-stress compound. The NADPH oxidase inhibitor apocynin induces
      the accumulation of endogenous NO in leaves of maize seedlings through a nitric
      oxide synthase (NOS)-like activity, and confers an augmented tolerance to UV-B
      induced oxidative damage. Here we propose a mechanism for the apocynin-induced NO
      increase in plants. NOS catalyzes the oxidation of arginine to citrulline and NO.
      It is suggested that apocynin inhibits arginase, the enzyme that hydrolyzes L
      arginine to urea and L-ornithine, increasing the arginine availability for
      arginine-dependent NO synthesis. Superoxide (O(2)(-)) is a strong NO scavenger
      due to its high reactivity with NO to give peroxynitrite (ONOO(-)). Superoxide is
      mainly produced by plant NADPH oxidase (pNOX). Inhibition of pNOX by apocynin at
      relatively high NO concentration, could reduces the formation of O(2)(-) and
      ONOO(-), increasing the availability of a huge amount of NO. We consider apocynin
      as a very attractive compound for studying NO-regulated processes in plants since
      it can replace the use of NO donors and overcome the subsequent technical
      problems.

PMID- 19847122
TI  - Auxin perception and polar auxin transport are not always a prerequisite for
      differential growth.
AB  - Using time-lapse photography, we studied the response kinetics of low light
      intensity-induced upward leaf-movement, called hyponastic growth, in Arabidopsis
      thaliana. This response is one of the traits of shade avoidance and directs plant
      organs to more favorable light conditions. Based on mutant- and pharmacological
      data we demonstrated that among other factors, functional auxin perception and
      polar auxin transport (PAT) are required for the amplitude of hyponastic growth
      and for maintenance of the high leaf angle, upon low light treatment. Here, we
      present additional data suggesting that auxin and PAT antagonize the hyponastic
      growth response induced by ethylene treatment. We conclude that ethylene- and low
      light-induced hyponastic growth occurs at least partly via separate signaling
      routes, despite their strong similarities in response kinetics.

PMID- 19847123
TI  - Constraints on plant signals and rewards to multiple mutualists?
AB  - Many plants invest substantial resources in signaling to and rewarding two kinds
      of 'interguild' mutualists, pollinators and seed dispersers. The signals and
      rewards are expressed via traits of flowers and fruits. Pollinators and seed
      dispersers could act in synergistic or antagonistic ways to influence selection
      on these traits. Here, we address the issue of whether plant species might be
      constrained in signaling to and rewarding multiple mutualists that provide
      different types of benefits to plants. Specifically, does investment in one type
      of mutualist limit investment in another? We examined the correlation between
      flower size and fruit size for 472 plant species spanning three regional floras.
      Our analyses made the assumption that structure size is related to plant
      investment in signals and/or rewards. We expect that a constraint due to
      interguild mutualisms would be evidenced by a negative correlation between flower
      and fruit size. Instead, we found significantly positive relationships between
      flower size and fruit size in all three regional floras. These relationships
      remained robust after correcting for plant evolutionary history using
      phylogenetically independent contrasts. These patterns may reflect synergies in
      selection by pollinators and seed dispersers, genetically-based or resource-based
      constraints on investment in reproductive tissues, and/or an underlying trade-off
      in structure size versus number.

PMID- 19847124
TI  - The ER body, a new organelle in Arabidopsis thaliana, requires NAI2 for its
      formation and accumulates specific beta-glucosidases.
AB  - Plants develop various ER-derived structures with specific functions. The ER body
      found in Arabidopsis thaliana is a spindle-shaped structure. ER bodies accumulate
      in epidermal cells in seedlings or are induced by wounding. The molecular
      mechanisms underlying the formation of the ER body remained obscure. We isolated
      an ER body-deficient mutant in Arabidopsis seedlings, which we termed nai2. The
      NAI2 gene encodes a member of a unique protein family. NAI2 localizes to the ER
      body and the downregulation of NAI2 elongates ER bodies and reduces their number.
      ER bodies specifically accumulate high levels of PYK10/BGLU23, which is a beta
      glucosidase that bears an ER retention signal. Additionally, in the nai2 mutant,
      PYK10 protein is diffuse throughout the ER and the PYK10 protein level is
      reduced. These observations indicate that NAI2 is a key factor for the formation
      of ER bodies and for the accumulation of PYK10 in the ER bodies of Arabidopsis.
      We also found that BGLU18, which encodes another beta-glucosidase with an ER
      retention signal, is induced at the site of wounding. Immunocytochemical analysis
      revealed that the BGLU18 protein is exclusively localized in ER bodies formed
      directly at the wounding site of cotyledons. These results suggest that BGLU18 is
      a component of the ER body in wounded leaves of Arabidopsis.

PMID- 19847126
TI  - The Rehabilitation Medicine Scientist Training Program: impact and lessons
      learned.
AB  - Physician scientists are seen as important in healthcare research. However, the
      number of physician scientists and their success in obtaining National Institutes
      of Health funding have been declining for many years. The shortage of physician
      scientists in Physical Medicine and Rehabilitation is particularly severe and can
      be attributed to many of the same factors that affect physician scientists in
      general, as well as to the lack of well-developed models for research training.
      In 1995, the Rehabilitation Medicine Scientist Training Program was funded by a
      K12 grant from the National Center for Medical Rehabilitation Research, as one
      strategy for increasing the number of research-productive physiatrists. The
      Rehabilitation Medicine Scientist Training Program's structure was revised in
      2001 to improve the level of preparation of incoming trainees and to provide a
      stronger central mentorship support network. We describe the original and revised
      structure of the Rehabilitation Medicine Scientist Training Program and review
      subjective and objective data on the productivity of the trainees who have
      completed the program. These data suggest that Rehabilitation Medicine Scientist
      Training Program trainees are, in general, successful in obtaining and
      maintaining academic faculty positions and that the productivity of the cohort
      trained after the revision, in particular, shows impressive growth after about 3
      yrs of training.

PMID- 19847128
TI  - Self-reported anabolic-androgenic steroids use and musculoskeletal injuries:
      findings from the center for the study of retired athletes health survey of
      retired NFL players.
AB  - OBJECTIVE: The relationship between musculoskeletal injuries and anabolic
      androgenic steroids is not well understood. The purpose of our study was to
      investigate the association between self-reported anabolic-androgenic steroids
      use and the prevalence of musculoskeletal injuries in a unique group of retired
      professional football players. DESIGN: A general health questionnaire was
      completed by 2552 retired professional football players. Survey data were
      collected between May 2001 and April 2003. Results of self-reported
      musculoskeletal injuries were compared with the use of anabolic-androgenic
      steroids using frequency distributions and chi2 analyses. RESULTS: Of the retired
      players, 9.1% reported using anabolic-androgenic steroids during their
      professional career. A total of 16.3% of all offensive line and 14.8% of all
      defensive line players reported using anabolic-androgenic steroids. Self-reported
      anabolic-androgenic steroids use was significantly associated (P < 0.05) with the
      following self-reported, medically diagnosed, joint and cartilaginous injuries in
      comparison with the nonanabolic-androgenic steroids users: disc herniations, knee
      ligamentous/meniscal injury, elbow injuries, neck stinger/burner, spine injury,
      and foot/toe/ankle injuries. There was no association between anabolic-androgenic
      steroids use and reported muscle/tendon injuries. CONCLUSIONS: Our findings
      demonstrate that an association may exist between anabolic-androgenic steroids
      use and the prevalence of reported musculoskeletal injury sustained during a
      professional football career, particularly ligamentous/joint-related injuries.
      There may also be an associated predisposition to selected types of injuries in
      anabolic-androgenic steroids users.

PMID- 19847127
TI  - Weight, rather than obesity distribution, explains peak external knee adduction
      moment during level gait.
AB  - OBJECTIVE: To determine whether a lower-body obesity pattern increases estimated
      forces on the medial compartment of the knee joint. DESIGN: Cross-sectional
      clinical biomechanical study. RESULTS: Nineteen normal weight (body mass index,
      22.8 +/- 1.8 kg/m2), 20 centrally obese (body mass index, 35.0 +/- 4.0 kg/m2 and
      waist-hip ratio >or=0.85 for women; >or=0.95 for men), and 20 lower-body obese
      (body mass index, 36.4 +/- 5.4 kg/m2) adults aged 37-55 yrs and without knee pain
      were recruited. There were no intergroup differences for age. Weight did not
      differ between obese groups, but thigh girth differed between groups (P <
      0.0001). In univariate analysis, both obesity group and thigh girth were
      significantly related to peak external knee adduction moment in mid-stance phase.
      However, in multivariate analysis after adjusting for weight, no statistically
      significant differences persisted using either obesity distribution or thigh
      girth as predictors. Weight was a significant predictor of external knee
      adduction moment, explaining 33% (P < 0.0001) of variance in external knee
      adduction moment for level gait. CONCLUSIONS: These data do not support a
      significant difference in knee medial compartment loading based on obesity
      distribution, but do support greater torque with higher weight. This suggests
      that the mechanism of obesity increasing risk for knee osteoarthritis may not be
      related to obesity distribution.

PMID- 19847129
TI  - The effect of body mass index and hip abductor brace use on inpatient
      rehabilitation outcomes after total hip arthroplasty.
AB  - OBJECTIVE: To determine the effect of body mass index and hip abductor brace use
      on inpatient rehabilitation outcomes after total hip replacement. DESIGN: This
      was a retrospective, comparative study of natural course of rehabilitation care
      in 15 inpatient rehabilitation facilities. Patients with total hip replacement (n
      = 1947) and inpatient rehabilitation were stratified into four body mass index
      groups: nonobese (body mass index <25 kg/m2), overweight (25-29.9 kg/m2),
      moderately obese (30-40 kg/m2), severely obese (body mass index >or=40 kg/m2),
      and further stratified by hip abductor brace (brace, no brace). The proportions
      of patients in each group who used hip abductor braces ranged from 14.5%-17.5%.
      The main outcomes were length of stay, functional independence measure scores,
      facility-related charges, and discharge destination. RESULTS: Length of stay was
      0.8-1.3 days longer in the body mass index <25 kg/m2 group compared with the
      remaining body mass index groups (P < 0.05). Average improvement in total and
      motor functional independence measure scores ranged 53%-58% and 74%-83% across
      groups (both P < 0.001). Total rehabilitation charges were highest in the <25
      kg/m2 body mass index group ($15,125 vs. $13,608-14,622; P < 0.0001). Hip brace
      use was associated with an average of $697 excess therapy/pharmacy charges during
      the rehabilitation stay, but no differences in other outcomes. CONCLUSIONS:
      Severe obesity and abductor brace use do not impair rehabilitation functional
      gains or discharge home, but is related with excess rehabilitation costs. Hip
      abduction braces do not seem necessary during rehabilitation, particularly for
      obese patients.

PMID- 19847130
TI  - The relationship between frontal plane gait variability and ankle range of motion
      in middle-aged and older persons with neuropathy.
AB  - OBJECTIVE: To explore the relationship between frontal plane ankle range of
      motion (ROM) and frontal plane control during gait, as determined by step-width
      variability and step-width range, among middle-aged and older persons with
      peripheral neuropathy (PN). DESIGN: Observational study of 39 adults (mean age +/
      standard deviation = 64.7 +/- 9.5 yrs) with PN. Demographic and clinical data,
      including measures of ankle ROM and PN severity, and spatiotemporal gait measures
      were obtained. Correlation and multivariate analyses were used to identify
      relationships between measures of ankle ROM and frontal plane gait variability.
      RESULTS: Significant negative correlations were identified between frontal plane
      ankle ROM (inversion + eversion), and step-width variability (r = -0.344; P =
      0.032) and step-width range (r = -0.386, P = 0.015). Multivariate analyses showed
      that the relationship between ankle ROM and step-width variability weakened in
      the presence of PN severity, with ROM and PN severity both demonstrating trends
      toward independent associations with step-width variability (P = 0.086 and 0.083,
      respectively; adjusted r2 = 0.145). However, ankle ROM demonstrated a stronger
      association with step-width range than did PN severity (P = 0.043 and 0.098,
      respectively; adjusted r2 = 0.169). CONCLUSIONS: Increased frontal plane ankle
      ROM is associated with decreased variability in frontal plane foot placement
      during gait among middle-aged and older persons with PN, a population at high
      risk for falls.

PMID- 19847132
TI  - Patients with chronic whiplash-associated disorders: relationship between
      clinical and psychological factors and functional health status.
AB  - OBJECTIVES: To examine the relative contribution of cervical impairments and
      psychosocial factors to perceived disability among people with chronic whiplash
      associated disorders. DESIGN: A total of 86 patients with chronic whiplash
      associated disorders participated in this observational, cross-sectional study.
      All patients were presented to outpatient physical therapy clinics. All patients
      completed the neck disability index. Depression, anxiety, and catastrophizing
      were measured with the Hospital Anxiety and Depression scale and the pain coping
      and cognition list, respectively. Cervical function was assessed by measuring the
      active range of motion. Stepwise and hierarchical regression analysis was used to
      estimate the contribution of cervical impairment and psychosocial functions to
      the variance in neck disability. RESULTS: Depressive symptomatology and
      catastrophizing explained 61% of the variance in neck disability index scores.
      Catastrophizing explained 57% of the variance in neck disability index scores and
      15% of the variance in the sum scores of active cervical rotations. CONCLUSIONS:
      Catastrophizing explained the variance in both perceived neck disability and, to
      a lesser extent, active range of cervical motion, which suggests that pain
      related catastrophizing plays an important role in the physical complaints of
      patients with chronic whiplash-associated disorders when referred to a physical
      therapist.

PMID- 19847131
TI  - Multisite trial on efficacy of constraint-induced movement therapy in children
      with hemiplegia: study design and methodology.
AB  - OBJECTIVE: In the past decades, several treatment approaches have been used to
      improve upper limb function in hemiplegic cerebral palsy. Only recently has
      constraint-induced movement therapy emerged as a treatment approach for children
      with hemiplegic cerebral palsy with the aim of reversing the behavioral
      suppression of movement in the affected upper limb. To date, evidence on this
      treatment has been very poor and limited, because all currently available trials
      reveal methodological limitations and a need for additional research to support
      the application of this treatment technique. This article presents the
      methodological choices, design, and main characteristics of an ongoing controlled
      clinical trial on the effectiveness and safety of constraint-induced movement
      therapy combined with an intensive rehabilitation program and compared with two
      comparison groups: one treated with an intensive rehabilitation program and the
      other with standard treatment. METHODS: Twenty-one rehabilitation sites are
      currently recruiting patients with hemiplegic cerebral palsy, aged between 2 and
      8 yrs, who have never undergone constraint therapy. Primary outcome measures
      include two major domains: upper limb motor ability (Quality of Upper Extremity
      Skills Test) and hand function assessment evaluating both grip function and
      spontaneous use of the affected side (Besta scale). Secondary outcome measures
      concern overall function, behavior, compliance, and satisfaction with treatment
      program of both child and family. Patients' follow-up is of 12 mos after
      treatment. RESULTS: Research in children has always been neglected in comparison
      with adults, because of ethical reasons regarding the use of children for
      experimental purposes. The consequence has been the utilization of treatment and
      assessment tools and techniques that have not always been tested in pediatric
      patients or evidence is very scarce. CONCLUSION: Discussing and working on
      pediatric research methods represents an urgent need in rehabilitation research.

PMID- 19847134
TI  - Brain mass incidentally noticed after minor head injury.

PMID- 19847135
TI  - Does stenting for atherosclerotic renovascular disease improve blood pressure and
      kidney function better than medical treatment?

PMID- 19847136
TI  - The effect of dialysis membrane type on plasma concentrations of pentosidine, a
      marker of carbonyl stress, in hemodialyzed patients.
AB  - INTRODUCTION: Advanced glycation end products (AGEs), which accumulate in plasma
      of hemodialyzed patients, participate in the development of complications
      associated with hemodialysis (HD). Carbonyl stress plays an essential role in the
      formation of AGEs, including pentosidine. OBJECTIVES: The aim of the study was to
      assess the effect of various low-flux dialysis membranes on plasma concentrations
      of total (P(tot)) and free (P(free)) pentosidine. PATIENTS AND METHODS: We
      examined 56 adult patients (aged 50 +/-13 years) on chronic HD. Plasma
      pentosidine concentrations were measured with high-performance liquid
      chromatography with fluorescence detection. Plasma proteins were subjected to
      acid hydrolysis or precipitation with trichloroacetic acid before measurement of
      P(tot) and P(free), respectively. RESULTS: Significantly lower concentrations of
      P(tot) were observed in patients dialyzed with polysulfone than non-polysulfone
      membranes before the HD session (22.0 +/-11.9 vs 34.4 +/-12.5 pmol/mg protein,
      respectively, p = 0.0008) and after the HD session (22.5 +/-12.9 vs 32.9 +/-12.0
      pmol/mg protein, p = 0.004). Moreover, there was a strong inverse correlation
      between the percentage of HD sessions performed with polysulfone membranes during
      the last 3 months and P(tot) concentration before HD (Rs = -0.44, p = 0.0011) and
      after HD (Rs = -0.45, p = 0.00073). CONCLUSIONS: The results suggest that
      polysulfone membranes reduce carbonyl stress more effectively than modified or
      unmodified cellulose membranes in patients on chronic HD. Determination of plasma
      pentosidine in hemodialyzed patients may help in comparing the physicochemical
      and biological properties of dialysis membranes. It may also contribute to the
      development of optimal strategies for renal replacement therapy.

PMID- 19847137
TI  - Glycemic profile and effectiveness and safety of insulin therapy in septic
      patients: is the blood glucose level sufficient?
AB  - INTRODUCTION: Hyperglycemia in sepsis is managed by intensive insulin therapy,
      which can cause hypoglycemia. OBJECTIVES: The aim of the study was to evaluate
      the glycemic profile as well as safety and effectiveness of a nurse-controlled
      insulin therapy protocol in patients with severe sepsis and septic shock.
      PATIENTS AND METHODS: The study included 16 septic patients who died
      (nonsurvivors) and 61 septic patients who survived. Glycemia was measured every 4
      h, and the dose of insulin infusion was adjusted to maintain glycemia of 4.4
      mmol/l to 8.3 mmol/l. We analyzed glycemia levels and daily variations, insulin
      dose, episodes of hypo- and hyperglycemia. RESULTS: Nonsurvivors and survivors
      had similar mean glycemia levels (7.38 vs. 7.08 mmol/l; p = 0.20) and insulin
      requirements (median [Me] = 26.9 vs. 23.9 units/d; p = 0.22; Me = 1.7 vs. 1.4
      units/h; p = 0.25). Daily glycemia variation (Me = 4.81 vs. 3.03 mmol/l; p
      <0.001), episodes of hypoglycemia (18.8% vs. 3.3%; p = 0.02), spontaneous severe
      hypoglycemia (12.5% vs. 0%; p = 0.006) and hyperglycemia (75.0% vs. 45.9%; p =
      0.04) were higher and more frequent in nonsurvivors. Three of 5393 blood samples
      (0.05%) met severe insulin-induced hypoglycemia criteria, and 74.4% of samples
      met the recommended range of 4.4-8.3 mmol/l. CONCLUSIONS: Patients who died
      experienced more episodes of hyperglycemia, spontaneous hypoglycemia and greater
      variation in the daily glycemia level. Daily glycemia variation is more reliable
      than a mean glycemic level in evaluating glucose homeostasis in septic patients.
      Few episodes of severe insulin-induced hypoglycemia occurred while using the
      nurse-controlled insulin therapy protocol.

PMID- 19847138
TI  - Metalloproteinases MMP-9, MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 in
      peripheral transbronchial lung biopsies of patients with sarcoidosis.
AB  - INTRODUCTION: The imbalance between metalloproteinases (MMPs) and their tissue
      inhibitors TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a
      granulomatous inflammatory disease which may lead to lung fibrosis. OBJECTIVES:
      The aim of the study was to verify whether the expression of MMP-9, MMP-2, TIMP
      1, and TIMP-2 in peripheral lung biopsies of patients with sarcoidosis correlate
      with lung function tests, radiological pattern, and bronchoalveolar lavage (BAL)
      cells. We compared the expression of MMPs and TIMPs between patients with sarcoid
      positive vs. - negative biopsy and fibrosing vs. non-fibrosing high-resolution
      computed tomography (HRCT)pattern. PATIENTS AND METHODS: We examined patients
      with histologically proven stage II and III sarcoidosis (n = 17).
      Immunohistochemistry with antibodies against the studied molecules was performed
      in the lung and bronchial tissue specimens obtained from transbronchial lung
      biopsies. The radiological pattern was evaluated based on HRCT. The total cell
      number and percentage of cells were calculated in the BAL samples. RESULTS: MMPs
      and TIMPs were present in the cells of sarcoid granuloma, and were more prevalent
      in the parenchyma than in the bronchi. We found no correlation between MMP-9, MMP
      2, TIMP-1, TIMP-2 and HRCT pattern or BAL cells. There were inverse associations
      between MMP-9 and FEV1 (% predicted), and also between MMP-2 and maximal
      expiratory flow 25-75% (L and % predicted) in patients with sarcoidosis diagnosed
      by transbronchial lung biopsy. There were no differences in the measured
      parameters between patients with and without fibrotic changes and between those
      with negative vs. positive lung biopsy results. CONCLUSIONS: Our study provides
      an indirect evidence for a potential involvement of MMPs/TIMPs in the sarcoid
      inflammation of the distal airways.

PMID- 19847139
TI  - Evidence for tissue factor expression in aortic valves in patients with aortic
      stenosis.
AB  - INTRODUCTION: The role of blood coagulation in the pathogenesis of aortic
      stenosis (AS) is unknown. Recently, tissue factor (TF) expression in stenotic
      aortic valves has been reported in animal model. OBJECTIVES: The aim of the study
      was to investigate TF expression in valve leaflets obtained from AS patients and
      to determine its associations with circulating coagulation markers and
      echocardiographic variables. PATIENTS AND METHODS: We studied 20 patients (10
      men, 10 women) with dominant AS (age 62.9 +/-9.6, years, mean gradient 43.62 +/
      14.62 mmHg), and 20 well-matched patients with dominant aortic insufficiency (AI)
      undergoing elective aortic valve replacement. Immunofluorescence was measured on
      decalcified leaflets using antibodies against human TF and macrophages.
      Prothrombin fragment 1+2 (F1+2) and circulating TF were determined in plasma
      prior to surgery. RESULTS: AS valves were characterized by an increased (all, p
      <0.001) percentage of TF-positive (24.6%) and macrophage-containing (27.3%) areas
      detected mainly on the aortic side of the leaflets, compared with AI valves (6.3%
      and 7.4%, respectively). Patients with AS had elevated F1+2 (262.1 +/-27.8
      pmol/l, p <0.001) and plasma TF (median 131.8, interquartile range [91.42-310.56]
      pg/ml, p = 0.018) compared with AI subjects (136.1 +/-11.9 pmol/l, 65.38 [49.51
      87.81] pg/ml, respectively). Percentage of TF-positive areas correlated with
      plasma TF (r = 0.68, p <0.0001), but not with F1+2. Maximum transvalvular
      gradient >75 mmHg, but not the aortic valve area, showed associations with
      percentage of TF-positive areas (r = 0.88, p = 0.0039). CONCLUSIONS: This study
      is the first full-length report demonstrating the presence of TF associated with
      macrophage infiltration in human aortic valve leaflets in AS patients.

PMID- 19847140
TI  - Should we prescribe blood pressure lowering drugs to every patient with advanced
      chronic kidney disease? A comment on two recent meta-analyses.
AB  - Antihypertensive treatment is an essential, life-prolonging measure in primary
      hypertension. It prevents apoplexy, myocardial infarction, and hypertensive
      kidney failure. Chronic kidney failure is associated with hypertension and an
      accelerated form of arteriosclerosis. Demise from cardiovascular affliction is a
      leading cause of death in renal patients (chronic renal failure stages II-IV,
      renal failure requiring dialysis, renal transplantation). What, then, is the role
      of antihypertensive treatment in such patients, and, specifically, what is
      achieved by renin-angiotensin-aldosterone (RAA) system modifying agents? Two meta
      analyses have recently investigated these issues. An article in The Lancet
      evaluated eight studies on dialysis patients (n = 1679). It concluded that
      antihypertensives are beneficial in reducing cardiovascular morbidity and
      mortality. However, we criticize these conclusions and show that the data are not
      convincingly in favor of antihypertensive treatment. A meta-analysis in the
      American Heart Journal assessed the role of antihypertensive agents and RAA
      system modifying drugs in 45,758 patients (from 25 studies), who were in stages I
      III of renal failure, i.e., not (yet) requiring dialysis. The authors claim that
      angiotensin- -converting enzyme inhibitors/angiotensin receptor blockers
      (ACEI/ARB) significantly reduced cardiovascular outcomes. However, our analysis
      of the data is not consistent with their conclusions. It showed that the results
      were quite mixed, that the authors may have overemphasized the positive results,
      and that considering all the results, it should be concluded that
      antihypertensive treatments, including those with ACEI/ARB, may not be superior
      to placebo (sic!) in renal patients. Rather than doing meta-analyses, larger
      primary studies are needed to reveal the real role of antihypertensive treatments
      in renal patients.

PMID- 19847141
TI  - Do alpha-reductase inhibitors prevent prostate cancer? 2008 practice guideline
      from the American society of clinical oncology and American urological
      association.
AB  - As new guidelines on the use of 5-alpha-reductase inhibitors (5-ARIs) for
      prostate cancer chemoprevention produced by the American Society of Clinical
      Oncology (ASCO) and American Urological Association (AUA) have recently been
      published, the use of 5-ARIs is becoming of increasing interest. We analyzed the
      current evidence to support the use of 5-ARIs in the prevention of prostate
      cancer. We therefore compared the new guidelines of the ASCO and AUA with the
      current data concerning the use of 5-ARIs in the prevention of prostate cancer.
      At present, there is still an open debate going on whether or not it is advisable
      to incorporate the use of 5-ARIs as chemopreventive agents in daily practice.

PMID- 19847142
TI  - Seasonal and pandemic influenza vaccines for the elderly and other risk groups: a
      review of available data.
AB  - Human seasonal influenza is a large burden of morbidity and mortality for
      societies, affecting mainly elderly people and those with underlying chronic
      medical conditions. Annual vaccination of older adults and other risk groups is
      the most effective measure for reducing morbidity and mortality associated with
      infection. A 2008 survey showed 40-fold differences between the vaccination
      coverage in various European Union countries in individuals aged >or=65 years,
      ranging from less that 2% to more than 80% in the 2006-2007 season, with Poland
      belonging to the countries with low influenza vaccination coverage. Annual
      monitoring of the vaccination coverage is crucial for achieving and maintaining
      high uptake levels. The need to pay for the vaccine out of pocket is a strong
      factor discouraging vaccination, and there is evidence that reimbursing costs of
      influenza vaccination influences vaccination coverage. Although annual influenza
      immunization of healthcare workers is an important method of preventing the
      nosocomial transmission of influenza and decreasing the exposure of vulnerable
      patients, worldwide influenza vaccination rates among healthcare personnel are
      unacceptably low, rarely exceeding 40%. It is important to keep high vaccination
      coverage among elderly nursing-home residents. More research is needed to clearly
      establish the effect of dose sparing strategies of influenza vaccination, e.g.,
      via intradermal immunization, on the immune response in elderly recipients.
      Finally, due to the emergence of the pandemic influenza A (H1N1) 2009 virus and
      the development of vaccines directed towards it, the upcoming influenza season
      2009-2010 will pose a particular challenge to influenza vaccination programs, and
      will require careful planning.

PMID- 19847143
TI  - How to diagnose and treat work-related asthma: key messages for clinical practice
      from the American college of chest physicians consensus statement.
AB  - Work-related asthma is common among adult asthmatics, either asthma initially
      caused by work (occupational asthma) or pre-existing asthma worsened by work
      factors (work-exacerbated asthma). Appropriate management depends on both correct
      diagnosis and on recognition of etiology. Following a systematic literature
      review, the American College of Chest Physicians enpaneled a group of experts
      that reviewed this material, extended the literature review, and developed a
      "Consensus Statement on the Diagnosis, and Management of Work-Related Asthma",
      published in 2008. This article addresses the main practical aspects of that
      Consensus Statement, including clinical clues to diagnosis of work-related asthma
      from the medical history, exposure assessment, targeted diagnostic tests, and
      directed patient management. The range and importance of preventive measures are
      also addressed.

PMID- 19847144
TI  - Should we target HDL cholesterol level in lowering cardiovascular risk?
AB  - In prospective observational studies and retrospective case control studies
      performed throughout the world, low serum levels of high-density lipoprotein
      cholesterol (HDL-C) are consistently associated with increased risk for all forms
      of atherosclerotic disease and its clinical sequelae, including myocardial
      infarction, stroke, and sudden death. In contrast, high serum levels of this
      lipoprotein are associated with reduced risk for these outcomes. The metabolism
      of high-density lipoproteins (HDLs) is complex, and a very large number of
      genetic polymorphisms influence the serum level of HDL particles in any given
      individual. A significant question in cardiovascular medicine is whether or not
      prospectively raising HDL in patients at risk is associated with significant
      reductions in cardiovascular events and rates of atherosclerotic disease
      progression. A recent comprehensive meta-analysis that incorporated the results
      of 108 prospective clinical trials suggests that the answer to this question is
      "no" with currently available lipid modifying therapies. However, a number of
      individual clinical trials and other meta-analyses suggest that, in fact, raising
      HDL does beneficially impact risk for cardiovascular events and slows progression
      or even reverses atherosclerosis. HDL appears to antagonize atherogenesis and
      drive a number of vasculoprotective phenomena. It has antioxidative, anti
      proliferative, anti-thrombotic, and anti-inflammatory properties and potentiates
      reverse cholesterol transport. Under some conditions, the proteosome of HDL can
      change, rendering it pro-inflammatory and pro-oxidative. This paper explores many
      of the key questions surrounding HDL-C and why probing its efficacy may not be
      entirely amenable to a meta-analysis. Numerous drugs are in development which
      have the capacity to raise HDL-C dramatically. It is hoped that these agents will
      be able to provide us with a more definitive answer about the clinical efficacy
      of raising HDL-C, and what specific approaches will be necessary in patients with
      specific genetic and metabolic backgrounds in both the primary and secondary
      prevention settings.

PMID- 19847145
TI  - Taurine bromamine: a new therapeutic option in inflammatory skin diseases.
AB  - Acne vulgaris is a multifactorial inflammatory skin disease. One of the
      pathogenic factors in acne is Propionibacterium acnes (P. acnes). Traditional
      treatment of acne lesions involves topical application of antibiotics with anti
      bacterial and anti-inflammatory properties. However, a failure of this therapy is
      widely associated with emergence of resistant bacteria. Therefore, a search for
      alternative topical anti-acne drugs is necessary. Taurine bromamine (TauBr), the
      physiological product of hypobromous acid reaction with taurine, shows
      antioxidant, anti-inflammatory, and anti-bacterial properties. Importantly, P.
      acnes, a potential pathogenic agent for acne vulgaris, is extremely sensitive to
      TauBr. In addition, TauBr inhibits the generation of H(2)O(2) by activated
      neutrophils, which seems to be crucial for reducing the number and severity of
      inflammatory acne lesions. All these data strongly support the concept of using
      TauBr for topical anti-acne therapy. In our pilot clinical study, we have
      compared the efficacy of TauBr cream with clindamycin gel, one of the most common
      topical agents used in the treatment of acne. After 6 weeks, both treatments
      produced comparable, beneficial results. More than 90% of patients improved
      clinically with similar reductions in a number of acne lesions (approximately
      65%). Therefore, the results from clinical studies are consistent with previous
      in vitro data and strongly suggest that TauBr could be considered a new
      therapeutic option in inflammatory acne.

PMID- 19847146
TI  - Idiopathic retroperitoneal fibrosis: case report.
AB  - A 45-year-old woman was admitted to the hospital because of abdominal pain,
      fever, and weight loss. Laboratory tests performed on admission revealed raised
      inflammatory markers. Ultrasonography of the abdomen showed dilatation of the
      pyelocalyceal system of the left kidney, while computed tomography showed
      retroperitoneal concentric periaortic mass extending to common iliac arteries and
      entrapping the left ureter. We established the diagnosis of idiopathic
      retroperitoneal fibrosis (RPF). JJ catheter was placed in the left ureter, and
      treatment with corticosteroids and azathioprine was started. Follow-up
      examinations showed a gradual improvement, namely a progressive remission of the
      retroperitoneal mass and normalization of both erythrocyte sedimentation rate and
      C-reactive protein concentration. Case reports, including our paper, and small
      case series showed azathioprine to be particularly effective in the treatment of
      RPF.

PMID- 19847147
TI  - Relapsing polychondritis: case report and literature review.
AB  - Relapsing polychondritis (RP) is a rare connective tissue disease which affects
      cartilaginous tissues of the nose, earlobes, respiratory tract, and joints, as
      well as proteoglycan-rich tissues including the media of the arteries, the
      conjunctiva and sclera of the eye. The disease is most common in patients aged 40
      60 years. It may for a long time cause unspecific signs (fever, malaise), which
      may cause a significant delay in establishing the diagnosis and initiating the
      ppropriate treatment. The mean time from symptom onset to diagnosis is 2.9 years.
      Steroids are the mainstay of therapy, but methotrexate and dapsone may also be
      beneficial in some patients. A case of RP presenting with fever, anemia, fatigue,
      arthritis, conjunctivitis, and auricular deformation is described. There were
      signs and symptoms suggestive of an infectious disease but no infection had been
      found, and despite tentative administration of antibiotics, the patient's
      condition steadily deteriorated. Eventually, the diagnosis was established based
      on McAdam's criteria. After intiating steroid therapy, the patient's condition
      improved significantly. We discuss the diagnostic criteria and treatment of this
      rare disease.

PMID- 19847148
TI  - Introduction and transmission of 2009 pandemic influenza A (H1N1) Virus--Kenya,
      June-July 2009.
AB  - In April 2009, in the United States, the first cases of 2009 pandemic influenza A
      (H1N1) virus infection were reported. On June 11, the World Health Organization
      (WHO) declared an influenza pandemic because of widespread transmission
      worldwide. As of September 13, all six WHO regions had reported approximately
      296,471 cases of pandemic H1N1, including 3,486 deaths. On June 29, the first
      case of pandemic H1N1 was confirmed in Kenya. At that time, only four other
      countries in sub-Saharan Africa had reported cases, and secondary transmission
      had not been documented in the region. Surveillance activities in Kenya detected
      four separate introductions of the virus into the country. The introductions
      provided an opportunity to study transmission of the virus (including calculation
      of secondary household attack rates) in a virus-naive population that had not yet
      initiated the use of antiviral drugs. This report describes the four
      introductions and the accompanying analysis. The overall rate of secondary
      household transmission of laboratory-confirmed pandemic H1N1 was 26% (range: 7%
      33%), which is comparable to secondary household attack rates reported for
      laboratory-confirmed seasonal influenza virus infection. However, additional and
      more rigorous studies are needed to better understand the secondary attack rates
      associated with the current pandemic.

PMID- 19847149
TI  - Reduction in rotavirus after vaccine introduction--United States, 2000-2009.
AB  - Worldwide, rotavirus is the leading cause of severe acute diarrhea in children
      aged <5 years. In the United States, before introduction of a live, oral
      pentavalent rotavirus vaccine (RV5) in 2006, rotavirus caused an estimated 20 to
      60 deaths, 55,000 to 70,000 hospitalizations, 205,000 to 272,000 emergency
      department visits, and 410,000 outpatient visits annually. Before 2000, rotavirus
      had a predictable winter-spring seasonality and geographic pattern in the United
      States, with activity beginning in the West census region during December
      January, extending across the country, and ending in the Northeast region during
      May-June. A similar but less pronounced trend was observed during 2000-2006. To
      characterize trends and compare the 2007-08 and 2008-09 rotavirus seasons with
      the prevaccine period 2000-2006, CDC analyzed data from the National Respiratory
      and Enteric Viruses Surveillance System (NREVSS). The results indicated that the
      2007-08 and 2008-09 seasons were both shorter and later than the median during
      2000-2006. The 2008-09 season had 15% more positive rotavirus test results than
      the 2007-08 season, but the number of positive test results during each season
      was substantially lower than the median observed during 2000-2006. Continued
      surveillance is needed to characterize the effect of routine childhood rotavirus
      vaccination on rotavirus disease in U.S. children.

PMID- 19847150
TI  - Progress toward poliomyelitis eradication--Nigeria, January 2008-July 2009.
AB  - Although wild poliovirus (WPV) cases in Nigeria decreased from 1,129 in 2006 to
      285 in 2007, Nigeria had the world's highest polio burden in 2008, with 798 (48%)
      of 1,651 WPV cases reported globally, including 721 (74%) of 976 WPV type 1
      (WPV1) cases. This report provides an update on progress toward polio eradication
      in Nigeria during 2008-2009 and activities planned to interrupt transmission.
      During 2008-2009, Nigeria was the source for WPV1 transmission to 11 countries
      and WPV type 3 (WPV3) transmission to four countries. In addition, transmission
      of circulating type 2 vaccine-derived poliovirus (cVDPV2) has been ongoing since
      2005. WPV1 cases decreased 87%, from 574 during January-July 2008 to 73 for the
      same period in 2009. However, WPV3 cases rose approximately six-fold, from 51
      during January-July 2008 to 303 during the same period in 2009, partly because of
      the increased emphasis on controlling WPV1. The decline in the proportion of
      children who have never received oral poliovirus vaccine (OPV) in the highest-
      incidence northern states, from 31% in 2006 to 11% in the first half of 2009
      indicates progress toward eradication. During 2008-2009, activities to accelerate
      polio eradication included use of mobile teams to vaccinate children not at home
      during supplemental immunization activities (SIAs), and efforts to increase
      political oversight and the engagement of community leaders. Sustained support of
      traditional, religious, and political leaders and improved implementation of SIAs
      will be needed to interrupt WPV and cVDPV2 transmission.

PMID- 19847151
TI  - Electrospinning fibrous polymer scaffolds for tissue engineering and cell
      culture.
AB  - As the field of tissue engineering evolves, there is a tremendous demand to
      produce more suitable materials and processing techniques in order to address the
      requirements (e.g., mechanics and vascularity) of more intricate organs and
      tissues. Electrospinning is a popular technique to create fibrous scaffolds that
      mimic the architecture and size scale of the native extracellular matrix. These
      fibrous scaffolds are also useful as cell culture substrates since the fibers can
      be used to direct cellular behavior, including stem cell differentiation (see
      extensive reviews by Mauck et al. and Sill et al. for more information). In this
      article, we describe the general process of electrospinning polymers and as an
      example, electrospin a reactive hyaluronic acid capable of crosslinking with
      light exposure (see Ifkovits et al. for a review on photocrosslinkable
      materials). We also introduce further processing capabilities such as
      photopatterning and multi-polymer scaffold formation. Photopatterning can be used
      to create scaffolds with channels and multi-scale porosity to increase cellular
      infiltration and tissue distribution. Multi-polymer scaffolds are useful to
      better tune the properties (mechanics and degradation) of a scaffold, including
      tailored porosity for cellular infiltration. Furthermore, these techniques can be
      extended to include a wide array of polymers and reactive macromers to create
      complex scaffolds that provide the cues necessary for the development of
      successful tissue engineered constructs.

PMID- 19847152
TI  - Asymmetrical dimethylarginine is associated with renal and cardiovascular
      outcomes and all-cause mortality in renal transplant recipients.
AB  - Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with
      endothelial dysfunction and predict the progression to dialysis and death in
      patients with chronic kidney disease. The effects of these increased ADMA levels
      in renal transplant recipients, however, are unknown. We used the data from
      ALERT, a randomized, double-blind, placebo-controlled study of the effect of
      fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant
      recipients with stable graft function on enrollment. Patients who were initially
      randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open
      label fluvastatin in a 2-year extension of the original study. After adjustment
      for baseline values for established factors in this post hoc analysis, ADMA was
      found to be a significant risk factor for graft failure or doubling of serum
      creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61),
      cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio
      4.87). In this trial extension, the number of end points increased with
      increasing quartiles of plasma ADMA levels. All end points were significantly
      increased in the fourth compared to the first quartile. Our study shows that
      elevated plasma levels of ADMA are associated with increased morbidity,
      mortality, and the deterioration of graft function in renal transplant
      recipients.

PMID- 19847154
TI  - In patients with type 1 diabetes and new-onset microalbuminuria the development
      of advanced chronic kidney disease may not require progression to proteinuria.
AB  - We sought to study new-onset microalbuminuria, its progression, and the decline
      of renal function in patients with type 1 diabetes. Using a cohort of 109
      patients who developed new-onset microalbuminuria in the first 4 years following
      enrollment in the 1st Joslin Kidney Study, we simultaneously tracked the change
      in their renal function and urinary albumin excretion. Of these, 79 patients were
      followed for an average of 12 years after microalbuminuria onset, wherein their
      glomerular filtration rate was estimated by the Modification of Diet in Renal
      Disease Study formula and compared with their microalbuminuria and proteinuria.
      The concordance between these outcomes was weak. Only 12 of the 23 patients who
      progressed to advanced (stage 3-5) chronic kidney disease developed proteinuria,
      which, in general, did not precede but accompanied the progression to advanced
      chronic kidney disease. The remaining 11 patients who developed advanced disease
      had persistent microalbuminuria or returned to normal albuminuria. Thus, we found
      that one-third of patients with type 1 diabetes developed advanced chronic kidney
      disease relatively soon after the onset of microalbuminuria and this was not
      conditional on the presence of proteinuria. Contrary to the existing concept of
      early nephropathy in type 1 diabetes, less emphasis should be placed on the
      mechanisms of progression to proteinuria and more placed on mechanisms initiating
      and promoting the early decline of renal function that eventually progresses to
      advanced chronic kidney disease.

PMID- 19847155
TI  - Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria
      in a large population cohort.
AB  - Urinary albumin excretion is a powerful predictor of progressive cardiovascular
      and renal disease. In rats and humans, administration of a synthetic vasopressin
      analogue, 1-desamino-8-D-arginine-vasopressin, increases urinary albumin
      excretion; however, it is unknown if endogenous vasopressin levels influence
      albumin excretion. To determine this we measured copeptin, a marker of endogenous
      vasopressin levels, and its association with urinary albumin excretion in 7593
      patients in the PREVEND study, a prospective population based, observational
      cohort. Urinary albumin excretion was measured in two consecutive 24-h urine
      samples by nephelometry while copeptin was measured by an immunoassay. Median
      copeptin concentrations were significantly higher in males than females and high
      levels were associated with significantly lower 24-h urine volumes of high
      osmolarity. With increasing quintiles of copeptin levels, the percentage of
      microalbuminuric subjects increased from 13 to 25 for males and from 8 to15 for
      females. This association was independent of age and other potential confounders;
      however, we found an interaction between age and copeptin in their association
      with urinary albumin excretion. Our study shows that plasma copeptin levels are
      associated with microalbuminuria, consistent with the hypothesis that vasopressin
      is involved in urinary albumin excretion. If future studies show that this
      association is causal, then drinking more water or pharmacological intervention
      to decrease plasma vasopressin may have beneficial effects on the kidney,
      especially in the elderly.

PMID- 19847153
TI  - The enigmatic parietal epithelial cell is finally getting noticed: a review.
AB  - Although the normal glomerulus comprises four resident cell types, least is known
      about the parietal epithelial cells (PECs). This comprehensive review addresses
      the cellular origin of PECs, discusses the normal structure and protein makeup of
      PECs, describes PEC function, and defines the responses to injury in disease and
      how these events lead to clinical events. The data show that PECs have unique
      properties and that new functions are being recognized such as their role in
      differentiating into podocytes during disease.

PMID- 19847156
TI  - KDIGO clinical practice guideline for the care of kidney transplant recipients: a
      summary.
AB  - The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice
      guideline on the monitoring, management, and treatment of kidney transplant
      recipients is intended to assist the practitioner caring for adults and children
      after kidney transplantation. The guideline development process followed an
      evidence-based approach, and management recommendations are based on systematic
      reviews of relevant treatment trials. Critical appraisal of the quality of the
      evidence and the strength of recommendations followed the Grades of
      Recommendation Assessment, Development, and Evaluation (GRADE) approach. The
      guideline makes recommendations for immunosuppression and graft monitoring, as
      well as prevention and treatment of infection, cardiovascular disease,
      malignancy, and other complications that are common in kidney transplant
      recipients, including hematological and bone disorders. Limitations of the
      evidence, especially the lack of definitive clinical outcome trials, are
      discussed and suggestions are provided for future research. This summary includes
      a brief description of methodology and the complete guideline recommendations but
      does not include the rationale and references for each recommendation, which are
      published elsewhere.

PMID- 19847157
TI  - Optimizing iohexol plasma disappearance curves to measure the glomerular
      filtration rate in children with chronic kidney disease.
AB  - Measuring the glomerular filtration rate (GFR) by iohexol plasma disappearance in
      children requires optimization of duration and sampling times since shortening
      the study may overestimate GFR. To determine these parameters, we analyzed
      iohexol plasma disappearance curves using multiple sampling points in each of 27
      children in the Chronic Kidney Disease in Children (CKiD) study. The GFR measured
      after 5 h was comparable to that after 6 h, but shortening to 4 h resulted in a
      significant 3% overestimation of GFR. We also sought to reduce the number of
      blood samples to determine GFR. This was done by adapting the Brochner-Mortensen
      equations to derive the relationship between a single-compartment two-sample
      (slow GFR model) disappearance curve and that from a double exponential analysis
      (two-compartment four-sample model) in the first clinic visit of 489 children.
      Using polynomial regression methods, we developed coefficients to accurately
      measure GFR from a single-compartment model. These coefficients were employed to
      recalculate the GFR and compare these to values measured with the two-compartment
      four-sample model in 361 of these children in their second clinic visit. There
      was excellent correlation (r=0.999) and no bias or change in between-individuals'
      dispersion. Hence, the GFR can be accurately measured in children with chronic
      kidney disease using the slow component of the iohexol plasma disappearance
      curve, provided the duration of study is at least 5 h.

PMID- 19847158
TI  - Linking an insect enzyme to hypertension: angiotensin II-epoxide hydrolase
      interactions.
AB  - Derived from arachidonic acid, epoxyeicosatrienoic acids function as
      antihypertensive and antihypertrophic mediators in the cardiovascular system.
      Epoxyeicosatrienoic acids are generated by soluble epoxide hydrolase, an enzyme
      hydrolyzing the epoxide moiety of juvenile hormones in insects, and are
      endothelium-derived hyperpolarizing factors that induce vessel dilation for
      cardioprotection. Pharmacological inhibition and genetic ablation of soluble
      epoxide hydrolase increases the level of epoxyeicosatrienoic acids. Recent
      findings suggest that the level of soluble epoxide hydrolase in the heart and
      endothelium is upregulated by angiotensin II in vitro in cultured cardiomyocytes
      and vascular endothelial cells and in vivo in rodent models. Treatment with
      soluble epoxide hydrolase-selective inhibitors in angiotensin II-infused
      hypertensive rats increases the level of epoxyeicosatrienoic acids, with
      attendant decrease in systolic blood pressure. Shear stress, the physiological
      stimulation of vessel dilation, downregulates soluble epoxide hydrolase and hence
      increases epoxyeicosatrienoic acid level in endothelial cells. Because of the
      close association of the angiotensin II/soluble epoxide
      hydrolase/epoxyeicosatrienoic acid system and blood pressure regulation,
      pharmacological inhibition of soluble epoxide hydrolase would be a useful
      approach to prevent and treat angiotensin II-induced cardiac hypertrophy and
      hypertension, as well as vascular impairments.

PMID- 19847159
TI  - Sex differences in social interaction in rats: role of the immediate-early gene
      zif268.
AB  - Given both the high prevalence of anxiety disorders in women and the fact that
      little is known about the mechanisms of gender differences in anxiety, our
      primary aim in this study was to investigate the neurobiological mechanisms
      underlying sex differences in social anxiety-like behavior in rats. Through the
      use of zif268 antisense oligodeoxynucleotides (zif ASO), we induced a temporary
      downregulation of zif268 expression in the medial prefrontal cortex of male and
      female rats and found that zif268 ASO male rats show more social anxiety-like
      behaviors when compared with control male rats in the social interaction test. In
      fact, zif268 ASO males displayed social anxiety-like behaviors, which were
      similar to control females, thus downregulation of zif268 expression in the mPFC
      of male rats eliminated sex differences previously found in the social anxiety
      like behavior tests. Interestingly, zif268 ASO in female rats had no effect on
      their social interaction. Our novel findings have led us to ascertain that
      sexually dimorphic zif268 expression in the mPFC is a key molecular factor in
      mediating sex-specific anxiety-like behavior in the social interaction test.

PMID- 19847160
TI  - Serotonergic and noradrenergic modulation of emotion processing by single dose
      antidepressants.
AB  - Serotonergic and noradrenergic pathways are the main targets of antidepressants.
      Their differential effects on emotion processing-related brain activation are,
      however, to be further characterized. We aimed at elucidating the neural sites of
      action of an acute differential serotonergic and noradrenergic influence on an
      emotion-processing task, which was earlier shown to be associated with
      depressiveness. In a single-blind pseudo-randomized crossover study, 21 healthy
      subjects (16 subjects finally included in the analysis) participated to ingest a
      single dose at three time points of either 40 mg citalopram, a selective
      serotonin-reuptake inhibitor, 8 mg reboxetine, a selective noradrenaline-reuptake
      inhibitor, or placebo 2-3 h before functional magnetic resonance imaging (fMRI).
      During fMRI, subjects performed a task comprising the anticipation and perception
      of pictures of either 'known' (positive, negative, neutral) or 'unknown' valence
      (randomly 50% positive or negative). In direct comparison with citalopram and
      with placebo, reboxetine increased brain activity in the medial thalamus.
      Citalopram modulated certain prefrontal and insular areas more prominently. Other
      frontal and parieto-occipital areas were modulated by both drugs. In conclusion,
      the functional network involved in emotional information processing could be
      modulated by the acute application of selective noradrenergic and serotonergic
      drugs revealing a noradrenergic effect in thalamic and frontal areas, and a
      prefrontal and insular focus of serotonergic modulation. These findings could
      have implications for future selection criteria concerning personalized
      antidepressant medication in depression.

PMID- 19847161
TI  - Dissociable control of impulsivity in rats by dopamine d2/3 receptors in the core
      and shell subregions of the nucleus accumbens.
AB  - Previous research has identified the nucleus accumbens (NAcb) as an important
      brain region underlying inter-individual variation in impulsive behavior. Such
      variation has been linked to decreased dopamine (DA) D2/3 receptor availability
      in the ventral striatum of rats exhibiting spontaneously high levels of
      impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual
      attention. This study investigated the involvement of DA D2/3 receptors in the
      NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the
      effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial
      agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats
      selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride
      increased significantly the level of impulsivity when infused into the NAcbS, but
      decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intra
      NAcb microinfusions of aripiprazole did not affect impulsivity. Systemic
      administration of nafadotride had no effect on impulsive behavior but increased
      the number of omissions and correct response latencies, whereas systemic
      injections of aripiprazole decreased impulsive and perseverative behavior, and
      increased the number of omissions and correct response latencies. These findings
      indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the
      NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and
      treatment of clinical disorders of behavioral control, including attention
      deficit hyperactivity disorder and drug addiction.

PMID- 19847163
TI  - Clinical trial simulations in pediatric patients using realistic covariates:
      application to teduglutide, a glucagon-like peptide-2 analog in neonates and
      infants with short-bowel syndrome.
AB  - Teduglutide, a synthetic glucagon-like peptide-2 (GLP-2) analog with activity
      relating to the regeneration, maintenance, and repair of the intestinal
      epithelium, is currently being evaluated for the treatment of short-bowel
      syndrome (SBS), Crohn's disease, and other gastrointestinal disorders. On the
      basis of promising results from teduglutide studies in adults with SBS and from
      studies in neonatal and juvenile animal models, a pediatric multiple-dose phase I
      clinical study was designed to determine the safety, efficacy, and
      pharmacokinetics of teduglutide in pediatric patients with SBS who have undergone
      resection for necrotizing enterocolitis, malrotation, or intestinal atresia. This
      report details the application of clinical trial simulations coupled with a novel
      approach using generalized additive modeling for location, scale, and shape
      (GAMLSS) that facilitates the simulation of demographic covariates specific to
      the targeted patient populations. The goal was to optimize phase I dosing
      strategies and the likelihood of achieving target exposure and therapeutic
      effect.

PMID- 19847162
TI  - Low doses of 17alpha-estradiol and 17beta-estradiol facilitate, whereas higher
      doses of estrone and 17alpha- and 17beta-estradiol impair, contextual fear
      conditioning in adult female rats.
AB  - Estrogens are known to exert significant structural and functional effects in the
      hippocampus of adult rodents. In particular, 17beta-estradiol can improve,
      impair, or have no effect on hippocampus-dependent learning and memory depending
      on dose and time of administration. The effects of other forms of estrogen, such
      as estrone and 17alpha-estradiol, on hippocampus-dependent learning have not been
      as thoroughly investigated. Therefore, the purpose of this study was to
      investigate the effects of 17beta-estradiol, estrone, and 17alpha-estradiol at
      three different doses on two different tasks: hippocampus-dependent contextual
      fear conditioning and hippocampus-independent cued fear conditioning. Adult
      ovariectomized female rats were injected with one of the estrogens at one of the
      three doses 30 mins before conditioning to assess the rapid effects of these
      estrogens on acquisition. Twenty-four hours later memory for the context was
      examined and 1 h later memory for the cue (tone) was assessed. Levels of
      synaptophysin were examined in the dorsal hippocampus of rats to identify a
      potential synaptic correlate of hormonal effects on contextual fear conditioning.
      Low 17beta-estradiol and 17alpha-estradiol enhanced, whereas high 17beta
      estradiol and 17alpha-estradiol impaired, contextual fear conditioning. Only the
      middle dose of estrone severely impaired contextual fear conditioning. Estrogens
      did not alter performance in the hippocampus-independent cued task. Synaptophysin
      expression was increased by estrone (at a middle and high dose) and 17beta
      estradiol (at a middle dose) in the CA3 region of the hippocampus and was not
      correlated with cognition. The results of this study indicate that estradiol can
      positively or negatively influence hippocampus-dependent learning and memory,
      whereas estrone impairs hippocampus-dependent learning and memory in a dose
      dependent manner. These results have important therapeutic implications, as
      estrone, a main component of a widely used hormone replacement therapy, was shown
      to have either a negative effect or no effect on learning and memory. It may be
      possible to use 17alpha-estradiol and lower doses of estrogens as potential
      alternatives in hormone replacement therapies.

PMID- 19847164
TI  - Mutation load and rapid adaptation favour outcrossing over self-fertilization.
AB  - The tendency of organisms to reproduce by cross-fertilization despite numerous
      disadvantages relative to self-fertilization is one of the oldest puzzles in
      evolutionary biology. For many species, the primary obstacle to the evolution of
      outcrossing is the cost of production of males, individuals that do not directly
      contribute offspring and thus diminish the long-term reproductive output of a
      lineage. Self-fertilizing ('selfing') organisms do not incur the cost of males
      and therefore should possess at least a twofold numerical advantage over most
      outcrossing organisms. Two competing explanations for the widespread prevalence
      of outcrossing in nature despite this inherent disadvantage are the avoidance of
      inbreeding depression generated by selfing and the ability of outcrossing
      populations to adapt more rapidly to environmental change. Here we show that
      outcrossing is favoured in populations of Caenorhabditis elegans subject to
      experimental evolution both under conditions of increased mutation rate and
      during adaptation to a novel environment. In general, fitness increased with
      increasing rates of outcrossing. Thus, each of the standard explanations for the
      maintenance of outcrossing are correct, and it is likely that outcrossing is the
      predominant mode of reproduction in most species because it is favoured under
      ecological conditions that are ubiquitous in natural environments.

PMID- 19847165
TI  - Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma.
AB  - NF-kappaB transcription factors function as crucial regulators of inflammatory
      and immune responses as well as of cell survival. They have also been implicated
      in cellular transformation and tumorigenesis. However, despite extensive
      biochemical characterization of NF-kappaB signalling during the past twenty
      years, the requirement for NF-kappaB in tumour development in vivo, particularly
      in solid tumours, is not completely understood. Here we show that the NF-kappaB
      pathway is required for the development of tumours in a mouse model of lung
      adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of
      oncogenic Kras(G12D) resulted in NF-kappaB activation in primary mouse embryonic
      fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and
      lacking p53, p53 restoration led to NF-kappaB inhibition. Furthermore, the
      inhibition of NF-kappaB signalling induced apoptosis in p53-null lung cancer cell
      lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour
      initiation or after tumour progression, resulted in significantly reduced tumour
      development. Together, these results indicate a critical function for NF-kappaB
      signalling in lung tumour development and, further, that this requirement depends
      on p53 status. These findings also provide support for the development of NF
      kappaB inhibitory drugs as targeted therapies for the treatment of patients with
      defined mutations in Kras and p53.

PMID- 19847168
TI  - Glowing worms elucidate neuronal signaling.

PMID- 19847166
TI  - Systematic RNA interference reveals that oncogenic KRAS-driven cancers require
      TBK1.
AB  - The proto-oncogene KRAS is mutated in a wide array of human cancers, most of
      which are aggressive and respond poorly to standard therapies. Although the
      identification of specific oncogenes has led to the development of clinically
      effective, molecularly targeted therapies in some cases, KRAS has remained
      refractory to this approach. A complementary strategy for targeting KRAS is to
      identify gene products that, when inhibited, result in cell death only in the
      presence of an oncogenic allele. Here we have used systematic RNA interference to
      detect synthetic lethal partners of oncogenic KRAS and found that the non
      canonical IkappaB kinase TBK1 was selectively essential in cells that contain
      mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer
      cell lines that depend on oncogenic KRAS expression. In these cells, TBK1
      activated NF-kappaB anti-apoptotic signals involving c-Rel and BCL-XL (also known
      as BCL2L1) that were essential for survival, providing mechanistic insights into
      this synthetic lethal interaction. These observations indicate that TBK1 and NF
      kappaB signalling are essential in KRAS mutant tumours, and establish a general
      approach for the rational identification of co-dependent pathways in cancer.

PMID- 19847169
TI  - Estrogen helps make mice male.

PMID- 19847172
TI  - Categorizing insufficient pain alleviation. Gap between D and E.

PMID- 19847173
TI  - Categorizing insufficient pain alleviation.

PMID- 19847174
TI  - Categorizing insufficient pain alleviation. Show me the regulation.

PMID- 19847175
TI  - Categorizing insufficient pain alleviation. To 'E' or not to 'E'.

PMID- 19847176
TI  - Categorizing insufficient pain alleviation. A word from OLAW and USDA.

PMID- 19847177
TI  - Exercise enclosures for guinea pigs.
AB  - Exercise and exploration are important to the health and happiness of guinea
      pigs. Laboratory housing does not always provide the space necessary for such
      opportunities. This article presents an inexpensive, versatile option for an
      enclosed exercise area for the laboratory guinea pig.

PMID- 19847179
TI  - The susceptibility of three strains of Chinese minipigs to diet-induced type 2
      diabetes mellitus.
AB  - Researchers have extensively used animal models to study diabetes mellitus. In
      this study, the authors determined the susceptibility of three strains of Chinese
      minipigs to diet-induced type 2 diabetes mellitus. For 8 months, the researchers
      fed Nongda control minipigs (n=4) a normal diet and fed Bama, Wuzhishan and
      Nongda minipigs (n=6 per group) a high-sucrose, high-fat diet. They measured the
      minipigs' body weights, fasting serum glucose concentrations and insulin
      concentrations each month. Every 2 months, they measured serum triglyceride,
      cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density
      lipoprotein cholesterol (LDL-C) levels and carried out intravenous glucose
      tolerance tests (IVGTTs). The Bama and Wuzhishan minipigs were relatively
      susceptible to diabetes induced by the high-sucrose, high-fat diet, though
      susceptibility differed among individual animals in the same strain. On the other
      hand, Nongda minipigs were relatively resistant to diet-induced diabetes. These
      results provide a foundation for diabetes-related genetic analyses in minipigs
      with high and low susceptibility to diet-induced type 2 diabetes.

PMID- 19847180
TI  - Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin
      dependent diabetes mellitus.
AB  - Yellow KK mice carrying the 'yellow obese' gene Ay are a well established
      polygenic model for human non-insulin dependent diabetes mellitus. These animals
      develop marked adiposity and decreased glucose tolerance relative to their
      control littermates, KK mice. The authors monitored glucose tolerance in KK-Ay
      mice over time and observed a significant (P<or=0.05) age-dependent improvement
      (13.3% by 175 d of age and 36.4% by 212 d of age, relative to 85 d of age).
      During the same time period, body weight and food and water consumption were
      relatively constant. The authors also measured plasma levels of endocrine
      hormones that are important in diabetes. Levels of insulin were approximately 8
      times higher and levels of amylin 3 times higher in 220-d-old KK-Ay mice than in
      180-d-old mice, whereas levels of glucagon-like peptide 1, glucagon and leptin
      remained relatively constant. These findings suggest that KK-Ay mice undergo an
      age-dependent improvement of glucose tolerance when maintained on a normal diet
      for 25 weeks or longer, due in part to increases in plasma levels of insulin and
      amylin.

PMID- 19847181
TI  - Simulating the fine-branch arboreal niche and exercising mice to elicit above
      branch quadrupedal grasping and climbing.
AB  - The fine-branch niche is a natural setting found among the slender vines and
      terminal branches of shrubs and tree canopies. In this study, the authors
      designed two simulations of this setting for laboratory mice. Their main goal was
      to model phenotypic plasticity in a small, clawed mammal, in order to better
      understand the effect of a thin-branch arboreal setting on musculoskeletal growth
      and behavior of these animals. The authors exposed mice to the smaller climbing
      setting for limited amounts of time (e.g., 30 min) and used the larger setting to
      permanently house another group of mice. Mice in both the limited and continuous
      climbing groups succeeded at quadrupedal climbing among a complex of thin branch
      segments. This led the authors to postulate that similarly sized pre-primates
      that lacked the unique features of today's primates could potentially have
      exploited this niche. The mice housed in the continuous model remained healthy
      and showed no signs of aggression, leading the authors to suggest that animal
      care personnel could use similar models as forms of enrichment for laboratory
      mice.

PMID- 19847182
TI  - An automated feeding and behavior monitoring system for rodents.
AB  - To develop pharmaceutical treatments for obesity and diabetes, researchers carry
      out food intake studies and more in-depth assessments of the feeding behavior in
      rodents. To facilitate such studies, the authors designed and developed a rodent
      behavior monitoring system that simultaneously measures food intake, water
      consumption and motor activity. When tested, their Automated Water Food Activity
      System (AWFAS) substantially increased throughput for routine rat food intake
      studies and also improved user ergonomics and safety. The authors describe their
      system and suggest that others could design similar systems or adapt certain
      features of the AWFAS to fit existing rodent caging systems.

PMID- 19847184
TI  - Comparison of one-side and bilateral intracavernosal papaverine injection on a
      Doppler study of the penis.
AB  - Intracavernosal injection of a vasodilating agent, followed by color Doppler
      ultrasonography of the penis, is used to diagnose vascular impotence. The
      vasodilating agent is usually injected into one of the corpora cavernosa and the
      peak systolic velocity (PSV) of the cavernosal arteries is measured on both
      sides, presuming that the connection between the two cavernosal bodies will
      distribute the drug uniformly on both sides and will consequently affect the
      cavernosal arteries and sinusoids equally. According to our experience, the PSV
      of the injection side is higher than that of the contralateral side. This
      difference could affect the results of the evaluation. In this study, our
      objective was to compare the results of both-side injections with those of one
      side injection. A total number of 60 patients with a normal Doppler study of the
      penis were enrolled in the study and were randomly divided into three groups. In
      the first and second group, 60 mg papaverine was injected into the right and left
      corpus cavernosa each. In the third group, half of the dose was injected into
      each side. The mean maximum PSV was measured and compared in each group. The mean
      maximum PSV in the group with the right-side injection was 47.7+/-10.8 and 40.3+/
      9.2 on the right and left side, respectively. The mean maximum PSV in the group
      with the left side injection was 44.4+/-7.1 and 51.4+/-7.1 on the right and the
      left side, respectively. The mean maximum PSV in the group with bilateral
      injection was 47+/-9.9 on the right side and 46.7+/-10.7 on the left side. In the
      first two groups, there was significant difference between the mean maximum PSV
      of the right and left cavernosal arteries, but in the third group, there was no
      significant difference between the mean maximum PSV of both side cavernosal
      arteries. Injecting papaverine in only one corpus cavernosum, despite a perfect
      postinjection manipulation of the penis, will affect the sinusoids and cavernosal
      artery at the same side of the injection more than the contralateral side. This
      results in a higher increase in the blood flow and PSV on that side and results
      in an artifactual difference between the velocity of the right and left side,
      which could ultimately exaggerate or mask the actual difference between the two
      sides. Dividing the total dose of the vasodilating agent and injecting half of
      the dose into each corpus cavernosum separately prevents artifactual difference
      between blood flow and velocity on the right and left side.

PMID- 19847185
TI  - Seven-month developmental outcomes of very low birth weight infants enrolled in a
      randomized controlled trial of delayed versus immediate cord clamping.
AB  - OBJECTIVE: The results from our previous trial revealed that infants with delayed
      cord clamping (DCC) had significantly lesser intraventricular hemorrhage (IVH)
      and late-onset sepsis (LOS) than infants with immediate cord clamping (ICC). A
      priori, we hypothesized that infants with DCC would have better motor function by
      7 months corrected age. STUDY DESIGN: Infants between 24 and 31 weeks were
      randomized to ICC or DCC and follow-up evaluation was completed at 7 months
      corrected age. RESULT: We found no differences in the Bayley Scales of Infant
      Development (BSID) scores between the DCC and ICC groups. However, a regression
      model of effects of DCC on motor scores controlling for gestational age, IVH,
      bronchopulmonary dysplasia, sepsis and male gender suggested higher motor scores
      of male infants with DCC. CONCLUSION: DCC at birth seems to be protective of very
      low birth weight male infants against motor disability at 7 months corrected age.

PMID- 19847186
TI  - Therapeutic hypothermia on neonatal transport: 4-year experience in a single
      NICU.
AB  - OBJECTIVE: Therapeutic hypothermia instituted within 6 h of birth has been shown
      to improve neurodevelopmental outcomes in term newborns with moderate-to-severe
      hypoxic-ischemic encephalopathy (HIE). The majority of infants who would benefit
      from cooling are born at centers that do not offer the therapy, and adding the
      time for transport will result in delays in therapy, that may lead to suboptimal
      or no neuroprotection for some patients. Our objective was to evaluate the effect
      of our center's experience with therapeutic hypothermia on neonatal transport.
      STUDY DESIGN: Retrospective review of all cases of therapeutic hypothermia at a
      single neonatal intensive care unit from 2005 to 2009. RESULT: Of 50 infants with
      HIE treated with hypothermia, 40 were outborn and 35 were cooled on transport.
      The majority of patients were passively cooled by the referring clinicians, then
      actively cooled by our transport team. Overcooling to <32 degrees C occurred in
      34% of patients, but there were no significant differences in admission vital
      signs or laboratory values between overcooled and appropriately cooled infants.
      The average time after birth of initiation of passive cooling was 1.4 h and
      active cooling was 2.7 h compared with the time of admission to our unit of 5.9
      h. CONCLUSION: We discuss the important aspects of our program, including the
      education of referring and receiving clinicians and avoidance of overcooling.

PMID- 19847187
TI  - Regulated on activation, normal T cell expressed and secreted and tumor necrosis
      factor-alpha in septic neonates.
AB  - OBJECTIVE: Measuring serum tumour necrosis factor-alpha (TNF-alpha) and Regulated
      upon Activation Normal T cell Expressed and Secreated (RANTES) in neonatal sepsis
      and determining whether early and late onset sepsis were associated with
      differences in their concentrations. STUDY DESIGN: In 15 neonates showing
      clinical signs of early- or late-onset infection, serum TNF-alpha and RANTES were
      determined at first suspicion of sepsis and before starting antibiotics. Fifteen
      healthy neonates were included as controls. RESULTS: Serum TNF-alpha white blood
      cells and C-reactive protein (CRP) were significantly higher, whereas RANTES was
      significantly lower in the septic group compared with the non-septic group. There
      was no significant difference in RANTES or TNF-alpha levels between infants
      having early or late-onset sepsis. Similar to term neonates, premature neonates,
      responded to infection with increased TNF-alpha and decreased RANTES, with no
      statistical differences between both groups. CONCLUSION: In this study TNF-alpha
      is the best diagnostic test of neonatal sepsis, followed by CRP, when evaluated
      at first suspicion of sepsis.

PMID- 19847188
TI  - Nasal intermittent positive pressure ventilation in the newborn: review of
      literature and evidence-based guidelines.
AB  - Various modes of nasal continuous positive airway pressure have been well
      established as a means of providing non-invasive respiratory support in the
      neonate. Recent reports suggest that nasal intermittent positive pressure
      ventilation may offer a better alternative, as a mode of non-invasive
      ventilation. This article will critically review the literature and provide some
      practical guidelines of the use of this technique in neonates.

PMID- 19847189
TI  - Improving parent satisfaction: an intervention to increase neonatal parent
      provider communication.
AB  - OBJECTIVE: The objective of the study was to assess whether a targeted
      intervention improved the satisfaction of neonatal parents with primary medical
      provider communication. STUDY DESIGN: The study design was a survey assessment of
      parents in a neonatal intensive care unit regarding their satisfaction with
      physician and nurse practitioner communication. Serial cohorts were surveyed
      before and after an intervention, including educating providers about family
      communication, distributing contact cards to families and showing a poster of
      providers in the unit. RESULT: More subjects in the post-intervention cohort
      (n=33) were satisfied (95%) with provider communication than in the pre
      intervention cohort (n=50, 74%; P<0.01). Parents who reported talking with a
      provider in the previous 7 days were more satisfied than parents who did not
      (P<0.001). After the intervention, fewer families (36 versus 65%) reported a
      desire for more frequent provider contact (P<0.01). CONCLUSION: A targeted
      intervention improved parent satisfaction with provider communication. Improving
      the quality and quantity of parent-provider communication increased parent
      satisfaction with communication with their baby's medical providers.

PMID- 19847191
TI  - Pemphigus vulgaris in White Europeans is linked with HLA Class II allele HLA
      DRB1*1454 but not DRB1*1401.

PMID- 19847190
TI  - KIT as a therapeutic target in melanoma.
AB  - Recently, genetic alterations activating the receptor tyrosine kinase KIT have
      been shown in some types of melanoma. KIT mutations can be successfully targeted
      by approved drugs in other cancers. Emerging evidence suggests that melanomas
      with KIT activation may also respond to KIT inhibitors that are already in
      clinical use. If confirmed in ongoing clinical trials, this experience would
      underscore the importance of recognizing the biological diversity among
      melanomas, representing a first decisive step toward the individualized and
      mechanism-based treatment of melanoma.

PMID- 19847192
TI  - ERK involvement in resistance to apoptosis in keratinocytes with mutant keratin.
AB  - The consequences of cell stress induced by misfolded proteins are an important
      contributor to many human diseases. One such disease is epidermolysis bullosa
      simplex (EBS), caused by mutations in the structural proteins (keratins K5 or
      K14) of the proliferative compartment of the epidermis (basal keratinocyte
      layer), leading to cell fragility and blistering. In severe EBS, the mutation is
      associated with aggregates of nonfilamentous keratin protein, and cell lines
      carrying such mutations show a constitutively activated stress response. Analysis
      of the cellular mechanisms leading to cell breakdown on physical stress may point
      the way to mutation-independent therapeutic approaches to these incurable genetic
      disorders. We therefore subjected EBS cell lines, immortalized from patients with
      EBS, to an oscillating mechanical stress in assays designed to mimic the physical
      trauma that leads to cell breakdown in vivo. These experiments show that
      mechanical stress activates extracellular signal-regulated kinase (ERK) signaling
      in these cells, and that the keratin mutant cells also show a resistance to
      apoptosis following mechanical stress that is reversed by inhibiting ERK. The
      consequences of constitutive expression of large amounts of defective structural
      protein in a tissue cell must be properly understood for the development of safe
      and effective therapies for these disorders.

PMID- 19847194
TI  - Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human
      neural progenitor cells.
AB  - Alternative splicing of pre-mRNA increases proteomic diversity, a crucial
      mechanism in defining tissue identity. We demonstrate differentially spliced
      interleukin (IL)-7 in distinct anatomic areas in the adult, in developing human
      brains and in normal human neuronal progenitor (NHNP) cells. IL-7c (c, the
      canonical form spanning all six exons) or its variants IL-7 delta 5, delta 4 or
      delta 4/5 were cloned and expressed as recombinant proteins. IL-7 and splice
      variants were able to shift the differentiation of NHNP cells as compared with
      the diluent control (P<0.01) defined by anti-beta (III)-tubulin and glial
      fibrillary acidic protein expression, with different degrees (IL-7c>delta 4/5>IL
      7 delta 5); IL-7 delta 4 exhibited a significantly weaker potency.
      Differentiation was confirmed by transcriptome analysis of IL-7c-stimulated
      neural NHNP cells, resulting in 58 differentially expressed genes; some of these
      are involved in neural differentiation, for example, the developmentally
      regulated transcription factor kruppel-like factor 12, musashi 2, a translational
      regulator of cell fate or the sonic hedgehog receptor patch 1. This suggests that
      IL-7 influences neural development at a molecular level by participating in human
      brain architecture through glia cell formation: a paradigm that alternative
      splicing in cytokines, for example, for IL-7, has a physiological role in human
      organ development and progenitor cell differentiation.

PMID- 19847193
TI  - European population substructure correlates with systemic lupus erythematosus
      endophenotypes in North Americans of European descent.
AB  - Previous work has demonstrated that Northern and Southern European ancestries are
      associated with specific systemic lupus erythematosus (SLE) manifestations. In
      this study, 1855 SLE cases of European descent were genotyped for 4965 single
      nucleotide polymorphisms and principal components analysis of genotype
      information was used to define population substructure. The first principal
      component (PC1) distinguished Northern from Southern European ancestry, PC2
      differentiated Eastern from Western European ancestry and PC3 delineated
      Ashkenazi Jewish ancestry. Compared with Northern European ancestry, Southern
      European ancestry was associated with autoantibody production (odds ratio
      (OR)=1.40, 95% confidence interval (CI) 1.07-1.83) and renal involvement (OR
      1.41, 95% CI 1.06-1.87), and was protective for discoid rash (OR=0.51, 95% CI
      0.32-0.82) and photosensitivity (OR=0.74, 95% CI 0.56-0.97). Both serositis
      (OR=1.46, 95% CI 1.12-1.89) and autoantibody production (OR=1.38, 95% CI 1.06
      1.80) were associated with Western compared to Eastern European ancestry.
      Ashkenazi Jewish ancestry was protective against neurologic manifestations of SLE
      (OR=0.62, 95% CI 0.40-0.94). Homogeneous clusters of cases defined by multiple
      PCs demonstrated stronger phenotypic associations. Genetic ancestry may
      contribute to the development of SLE endophenotypes and should be accounted for
      in genetic studies of disease characteristics.

PMID- 19847195
TI  - The effects of the PPAR-gamma agonist pioglitazone on plasma concentrations of
      circulating vasoactive factors in type II diabetes mellitus.

PMID- 19847196
TI  - The expression levels of the pro-apoptotic XAF-1 gene modulate the cytotoxic
      response to Nutlin-3 in B chronic lymphocytic leukemia.

PMID- 19847197
TI  - Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic
      leukemia.
AB  - RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase
      family that functions as a regulator of thymocyte development and T-cell receptor
      signaling by facilitating localization of zeta-chain-associated protein kinase 70
      (ZAP70) to the immunological synapse. Here we investigated the function of RhoH
      in the B-cell lineage. B-cell receptor (BCR) signaling was intact in Rhoh(-/-)
      mice. Because RhoH interacts with ZAP70, which is a prognostic factor in B-cell
      chronic lymphocytic leukemia (CLL), we analyzed the mRNA levels of RhoH in
      primary human CLL cells and showed a 2.3-fold higher RhoH expression compared
      with normal B cells. RhoH expression in CLL positively correlated with the
      protein levels of ZAP70. Deletion of Rhoh in a murine model of CLL (Emu-TCL1(Tg)
      mice) significantly delayed the accumulation of CD5(+)IgM(+) leukemic cells in
      peripheral blood and the leukemic burden in the peritoneal cavity, bone marrow
      and spleen of Rhoh(-/-) mice compared with their Rhoh(+/+) counterparts.
      Phosphorylation of AKT and ERK in response to BCR stimulation was notably
      decreased in Emu-TCL1(Tg);Rhoh(-/-) splenocytes. These data suggest that RhoH has
      a function in the progression of CLL in a murine model and show RhoH expression
      is altered in human primary CLL samples.

PMID- 19847198
TI  - The JAK2 46/1 haplotype confers susceptibility to essential thrombocythemia
      regardless of JAK2V617F mutational status-clinical correlates in a study of 226
      consecutive patients.
AB  - The germline JAK2 haplotype 46/1, tagged by the 'C' allele of single-nucleotide
      polymorphism (SNP) rs12343867 (C/T), has been associated with JAK2V617F (VF)
      positive myeloproliferative neoplasms. SNP rs12343867 was genotyped using bone
      marrow DNA in 226 consecutive patients with essential thrombocythemia (ET) with
      concomitant analysis of VF allele burden. The incidence of the 46/1-linked C
      allele was significantly higher in ET (genotype: CC 15%, CT 52%, TT 33%; C-allele
      frequency: 41%) than in population controls (P<0.01). Genotype distributions were
      similar among VF-positive/VF-negative patients (genotype: CC 18/11%, CT 52/53%,
      TT 30/36%; C-allele: 44/38%; P=0.29). Haplotype 46/1 frequency was remarkably
      similar when comparing VF-negative patients to those with <10% VF allele burden,
      but significantly higher in the presence of >10% VF allele burden (genotype: CC
      11/13/38%, CT 53/56/38%, TT 36/31/24%; C-allele frequency: 38/41/57%; P<0.01).
      The clinical features of 46/1-positive and -negative ET were indistinguishable,
      including blood counts, rate of thrombosis/disease transformation and survival.
      We conclude that JAK2 haplotype 46/1 confers susceptibility to developing ET
      independent of VF mutational status and does not seem to further affect the
      clinical phenotype or prognosis.

PMID- 19847199
TI  - JAK2 germline genetic variation affects disease susceptibility in primary
      myelofibrosis regardless of V617F mutational status: nullizygosity for the JAK2
      46/1 haplotype is associated with inferior survival.
AB  - A common JAK2 germline haplotype (46/1) has been associated with JAK2V617F (VF)
      positive myeloproliferative neoplasms. The rs12343867 SNP (C/T) tags this
      haplotype. A total of 130 patients (77 VF-positive) with primary myelofibrosis
      (PMF) were analyzed for this informative SNP, using bone marrow-derived DNA. The
      observed 46/1 C allele frequencies in VF-positive (50%) and VF-negative (36%)
      patients were both significantly higher than expected in population controls
      (P<0.01). Genotype distributions in VF-positive/VF-negative patients were CC
      31%/9%, CT 38%/53% and TT 31%/38% (P=0.01). CC genotype/C-allele frequencies in
      patients with <20% VF mutation burden (12%/37%) were similar (P=0.95) to those
      seen in VF-negative patients (9%/36%), but were significantly lower (P<0.01) than
      those seen in the presence of >50% mutation burden ( approximately 67%/71%). The
      rs12343867 genotype did not correlate with the International Prognostic Scoring
      System (IPSS) score or karyotype. Unexpectedly, the TT genotype was associated
      with shortened survival (P<0.01), which was not accounted for by IPSS score or VF
      allele burden. We conclude that JAK2 germline genetic variation affects disease
      susceptibility, and possibly survival, in PMF, regardless of VF mutational
      status. Allelic distortion from acquired uniparental disomy contributes to the
      appearance of a more pronounced effect on disease susceptibility in VF-positive
      patients, when studying clonally affected tissue.

PMID- 19847200
TI  - Influence of NPM1 and FLT3-ITD status on outcome in relapsed/refractory AML
      patients receiving salvage therapy including gemtuzumab ozogamicin.

PMID- 19847201
TI  - Aberrant telomere structure is characteristic of resistant chronic lymphocytic
      leukaemia cells.

PMID- 19847202
TI  - Wilms tumor 1 (WT1) gene mutations in pediatric T-cell malignancies.

PMID- 19847203
TI  - Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants
      in eliciting antigen-specific immunity in vivo.
AB  - A hurdle facing DNA vaccine development is the ability to generate strong immune
      responses systemically and at local immune sites. We report a novel systemically
      administered DNA vaccination strategy using intramuscular codelivery of CCL27 or
      CCL28, which elicited elevated peripheral IFN-gamma and antigen-specific IgG
      while driving antigen-specific T-cell secretion of cytokine and antibody
      production in the gut-associated lymphoid tissue and lung. This strategy resulted
      in induction of long-lived antibody responses that neutralized influenza A/PR8/34
      and protected mice from morbidity and mortality associated with a lethal
      intranasal viral challenge. This is the first example of the use of CCL27 and
      CCL28 chemokines as adjuvants to influence a DNA vaccine strategy, suggesting
      further examination of this approach for manipulation of vaccine-induced immunity
      impacting both quality and phenotype of responses.

PMID- 19847204
TI  - Mechanisms controlling titer and expression of bidirectional lentiviral and
      gammaretroviral vectors.
AB  - Bidirectional lentiviral vectors mediate expression of two or more cDNAs from a
      single internal promoter. In this study, we examined mechanisms that control
      titer and expression properties of this vector system. To address whether the
      bidirectional design depends on lentiviral (LV) backbone components, especially
      the Rev/Rev responsive element (RRE) system, we constructed similar expression
      cassettes for LV and gammaretroviral (GV) vectors. Bidirectional expression
      levels could be adjusted by the use of different internal promoters. Furthermore,
      removal of the constitutive RNA transport element of Mason-Pfizer monkey virus,
      used in first generation bidirectional LV vectors, improved gene expression.
      Titers of bidirectional vectors were approximately 10-fold reduced in comparison
      to unidirectional vectors, independent of the Rev/RRE interaction. We reasoned
      that titer reductions were due to the formation of interfering double-stranded
      RNA in packaging cells. Indeed, cotransfection of Nodamuravirus B2 protein, an
      RNA interference suppressor, increased bidirectional vector titers at least
      fivefold. We validated the potential of high titer bidirectional vectors by
      coexpressing a fluorescent marker with O(6)-methylguanine-DNA methyltransferase
      from integrating, or with Cre recombinase from integrating and non-integrating GV
      and LV backbones. This allowed for the tracking of chemoprotected and recombined
      cells by fluorescence marker expression.

PMID- 19847206
TI  - Integrase-defective lentiviral vectors: progress and applications.
AB  - Lentiviral vectors (LVs) offer the advantages of a large packaging capacity,
      broad cell tropism or specific cell-type targeting through pseudotyping, and long
      term expression from integrated gene cassettes. However, transgene integration
      carries a risk of disrupting gene expression through insertional mutagenesis and
      may not be required for all applications. A non-integrating LV may be beneficial
      in cases in which transient gene expression is desired. Several recent
      publications outline the development and initial biological characterization of
      such vectors. Here, we discuss the potential applications and new directions for
      the development of integration-defective LVs.

PMID- 19847205
TI  - Effect of nuclear localization and hydrodynamic delivery-induced cell division on
      phiC31 integrase activity.
AB  - Phage phiC31 integrase is a recombinase that can be expressed in mammalian cells
      to integrate plasmids carrying an attB sequence into the genome at specific
      pseudo attP locations. We show by immunofluoresence that wild-type phiC31
      integrase is cytoplasmic and that addition of the SV40 nuclear localization
      signal (NLS) localized phiC31 integrase to the nucleus. Unexpectedly, the NLS
      depressed integration efficiency in HeLa cells and provided no benefit when used
      to integrate the human Factor IX (hFIX) gene into mouse liver. As breakdown of
      the nuclear membrane during mitosis could allow cytoplasmic integrase access to
      the chromosomes, we analyzed whether cell division was required for integration
      into liver cells in vivo. Hepatocytes were labeled with iododeoxyuridine to mark
      cells that underwent DNA replication during the week after hydrodynamic
      injection. Hydrodynamic delivery led to DNA replication in one-third of
      hepatocytes. Approximately three out of four cells having phiC31 integrase
      mediated stable hFIX expression did not undergo replication, indicating that cell
      division was not required for integrase function in liver. Therefore, although
      the bulk of phiC31 integrase protein seems to be cytoplasmic in mammalian cells,
      integration can still occur in the nucleus, even without cell division.

PMID- 19847207
TI  - Global ecological patterns in uncultured Archaea.
AB  - We have applied a global analytical approach to uncultured Archaea that for the
      first time reveals well-defined community patterns along broad environmental
      gradients and habitat types. Phylogenetic patterns and the environmental factors
      governing the creation and maintenance of these patterns were analyzed for c.
      2000 archaeal 16S rRNA gene sequences from 67 globally distributed studies. The
      sequences were dereplicated at 97% identity, grouped into seven habitat types,
      and analyzed with both Unifrac (to explore shared phylogenetic history) and
      multivariate regression tree (that considers the relative abundance of the
      lineages or taxa) approaches. Both phylogenetic and taxon-based approaches showed
      salinity and not temperature as one of the principal driving forces at the global
      scale. Hydrothermal vents and planktonic freshwater habitats emerged as the
      largest reservoirs of archaeal diversity and consequently are promising
      environments for the discovery of new archaeal lineages. Conversely, soils were
      more phylogenetically clustered and archaeal diversity was the result of a high
      number of closely related phylotypes rather than different lineages. Applying the
      ecological concept of 'indicator species', we detected up to 13 indicator
      archaeal lineages for the seven habitats prospected. Some of these lineages (that
      is, hypersaline MSBL1, marine sediment FCG1 and freshwater plSA1), for which
      ecological importance has remained unseen to date, deserve further attention as
      they represent potential key archaeal groups in terms of distribution and
      ecological processes. Hydrothermal vents held the highest number of indicator
      lineages, suggesting it would be the earliest habitat colonized by Archaea.
      Overall, our approach provided ecological support for the often arbitrary
      nomenclature within uncultured Archaea, as well as phylogeographical clues on key
      ecological and evolutionary aspects of archaeal biology.

PMID- 19847209
TI  - Silk production from tarantula feet questioned.
AB  - As with all spiders, tarantulas spin silk from specialized structures in the
      abdomen called spinnerets, which are key features unique to the group. Recently
      Gorb et al. reported that the zebra tarantula Aphonopelma seemanni also secretes
      silk from its feet, which might improve its ability to climb on vertical
      surfaces. Here we show that when the spinnerets are experimentally sealed, the
      zebra tarantula cannot secrete silk or similar threads, disagreeing with previous
      reports by Gorb et al.. Additional evidence also disagrees with leg secretion of
      silk.

PMID- 19847214
TI  - Climate of compromise.

PMID- 19847215
TI  - Russia's grand plan.

PMID- 19847222
TI  - Journal club. An oceanographer marvels at the good timing of shrimp.

PMID- 19847228
TI  - Time running out for climate talks.

PMID- 19847229
TI  - Hwang verdict imminent.

PMID- 19847230
TI  - High hopes for Russia's nanotech firms.

PMID- 19847231
TI  - Hazy goals hold up conservation.

PMID- 19847232
TI  - Europe's Galileo project gains ground.

PMID- 19847234
TI  - Fossil primate challenges Ida's place.

PMID- 19847236
TI  - Transgenic aubergines put on ice.

PMID- 19847237
TI  - Climate: When the ice melts.

PMID- 19847238
TI  - Climate: Counting carbon in the Amazon.

PMID- 19847239
TI  - Sharing: guidelines go one step forwards, two steps back.

PMID- 19847240
TI  - Sharing: public databases combat mistrust and secrecy.

PMID- 19847241
TI  - UK red tape as sticky as the US version for would-be students.

PMID- 19847242
TI  - Sharing: project will make climate data freely available to all.

PMID- 19847243
TI  - India pushes for common responsibility.

PMID- 19847244
TI  - China expects leadership from rich nations.

PMID- 19847245
TI  - Copenhagen needs a strong lead negotiator.

PMID- 19847247
TI  - Q&A: The science of persuasion. Interview by Sanjay Khanna.

PMID- 19847249
TI  - Q&A: Architect of a sustainable future. Interview by John Whitfield.

PMID- 19847250
TI  - Chemical physics: Molecular conformations fielded.

PMID- 19847251
TI  - Solar system: Saturn's colossal ring.

PMID- 19847252
TI  - Climate change: Early survival of Antarctic ice.

PMID- 19847253
TI  - Ecology: Kelp in postglacial time.

PMID- 19847254
TI  - Molecular biology: Slip sliding on DNA.

PMID- 19847256
TI  - Biochemistry: Enzyme's black box cracked open.

PMID- 19847257
TI  - Microscopy: Light from the dark.

PMID- 19847258
TI  - The DNA-damage response in human biology and disease.
AB  - The prime objective for every life form is to deliver its genetic material,
      intact and unchanged, to the next generation. This must be achieved despite
      constant assaults by endogenous and environmental agents on the DNA. To counter
      this threat, life has evolved several systems to detect DNA damage, signal its
      presence and mediate its repair. Such responses, which have an impact on a wide
      range of cellular events, are biologically significant because they prevent
      diverse human diseases. Our improving understanding of DNA-damage responses is
      providing new avenues for disease management.

PMID- 19847260
TI  - Information causality as a physical principle.
AB  - Quantum physics has remarkable distinguishing characteristics. For example, it
      gives only probabilistic predictions (non-determinism) and does not allow copying
      of unknown states (no-cloning). Quantum correlations may be stronger than any
      classical ones, but information cannot be transmitted faster than light (no
      signalling). However, these features do not uniquely define quantum physics. A
      broad class of theories exist that share such traits and allow even stronger
      (than quantum) correlations. Here we introduce the principle of 'information
      causality' and show that it is respected by classical and quantum physics but
      violated by all no-signalling theories with stronger than (the strongest) quantum
      correlations. The principle relates to the amount of information that an observer
      (Bob) can gain about a data set belonging to another observer (Alice), the
      contents of which are completely unknown to him. Using all his local resources
      (which may be correlated with her resources) and allowing classical communication
      from her, the amount of information that Bob can recover is bounded by the
      information volume (m) of the communication. Namely, if Alice communicates m bits
      to Bob, the total information obtainable by Bob cannot be greater than m. For m =
      0, information causality reduces to the standard no-signalling principle.
      However, no-signalling theories with maximally strong correlations would allow
      Bob access to all the data in any m-bit subset of the whole data set held by
      Alice. If only one bit is sent by Alice (m = 1), this is tantamount to Bob's
      being able to access the value of any single bit of Alice's data (but not all of
      them). Information causality may therefore help to distinguish physical theories
      from non-physical ones. We suggest that information causality-a generalization of
      the no-signalling condition-might be one of the foundational properties of
      nature.

PMID- 19847259
TI  - Pten in stromal fibroblasts suppresses mammary epithelial tumours.
AB  - The tumour stroma is believed to contribute to some of the most malignant
      characteristics of epithelial tumours. However, signalling between stromal and
      tumour cells is complex and remains poorly understood. Here we show that the
      genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands
      accelerated the initiation, progression and malignant transformation of mammary
      epithelial tumours. This was associated with the massive remodelling of the
      extracellular matrix (ECM), innate immune cell infiltration and increased
      angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression,
      phosphorylation (T72) and recruitment of Ets2 to target promoters known to be
      involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted
      tumours ameliorated disruption of the tumour microenvironment and was sufficient
      to decrease tumour growth and progression. Global gene expression profiling of
      mammary stromal cells identified a Pten-specific signature that was highly
      represented in the tumour stroma of patients with breast cancer. These findings
      identify the Pten-Ets2 axis as a critical stroma-specific signalling pathway that
      suppresses mammary epithelial tumours.

PMID- 19847261
TI  - Imaging chromophores with undetectable fluorescence by stimulated emission
      microscopy.
AB  - Fluorescence, that is, spontaneous emission, is generally more sensitive than
      absorption measurement, and is widely used in optical imaging. However, many
      chromophores, such as haemoglobin and cytochromes, absorb but have undetectable
      fluorescence because the spontaneous emission is dominated by their fast non
      radiative decay. Yet the detection of their absorption is difficult under a
      microscope. Here we use stimulated emission, which competes effectively with the
      nonradiative decay, to make the chromophores detectable, and report a new
      contrast mechanism for optical microscopy. In a pump-probe experiment, on
      photoexcitation by a pump pulse, the sample is stimulated down to the ground
      state by a time-delayed probe pulse, the intensity of which is concurrently
      increased. We extract the miniscule intensity increase with shot-noise-limited
      sensitivity by using a lock-in amplifier and intensity modulation of the pump
      beam at a high megahertz frequency. The signal is generated only at the laser
      foci owing to the nonlinear dependence on the input intensities, providing
      intrinsic three-dimensional optical sectioning capability. In contrast,
      conventional one-beam absorption measurement exhibits low sensitivity, lack of
      three-dimensional sectioning capability, and complication by linear scattering of
      heterogeneous samples. We demonstrate a variety of applications of stimulated
      emission microscopy, such as visualizing chromoproteins, non-fluorescent variants
      of the green fluorescent protein, monitoring lacZ gene expression with a
      chromogenic reporter, mapping transdermal drug distributions without histological
      sectioning, and label-free microvascular imaging based on endogenous contrast of
      haemoglobin. For all these applications, sensitivity is orders of magnitude
      higher than for spontaneous emission or absorption contrast, permitting
      nonfluorescent reporters for molecular imaging.

PMID- 19847262
TI  - Trench-parallel anisotropy produced by serpentine deformation in the hydrated
      mantle wedge.
AB  - Seismic anisotropy is a powerful tool for detecting the geometry and style of
      deformation in the Earth's interior, as it primarily reflects the deformation
      induced preferred orientation of anisotropic crystals. Although seismic
      anisotropy in the upper mantle is generally attributed to the crystal-preferred
      orientation of olivine, the strong trench-parallel anisotropy (delay time of one
      to two seconds) observed in several subduction systems is difficult to explain in
      terms of olivine anisotropy, even if the entire mantle wedge were to act as an
      anisotropic source. Here we show that the crystal-preferred orientation of
      serpentine, the main hydrous mineral in the upper mantle, can produce the strong
      trench-parallel seismic anisotropy observed in subduction systems. High-pressure
      deformation experiments reveal that the serpentine c-axis tends to rotate to an
      orientation normal to the shear plane during deformation; consequently, seismic
      velocity propagating normal to the shear plane (plate interface) is much slower
      than that in other directions. The seismic anisotropy estimated for deformed
      serpentine aggregates is an order of magnitude greater than that for olivine, and
      therefore the alignment of serpentine in the hydrated mantle wedge results in a
      strong trench-parallel seismic anisotropy in the case of a steeply subducting
      slab. This hypothesis is also consistent with the presence of a hydrous phase in
      the mantle wedge, as inferred from anomalously low seismic-wave velocities.

PMID- 19847263
TI  - Convergent evolution of anthropoid-like adaptations in Eocene adapiform primates.
AB  - Adapiform or 'adapoid' primates first appear in the fossil record in the earliest
      Eocene epoch ( approximately 55 million years (Myr) ago), and were common
      components of Palaeogene primate communities in Europe, Asia and North America.
      Adapiforms are commonly referred to as the 'lemur-like' primates of the Eocene
      epoch, and recent phylogenetic analyses have placed adapiforms as stem members of
      Strepsirrhini, a primate suborder whose crown clade includes lemurs, lorises and
      galagos. An alternative view is that adapiforms are stem anthropoids. This debate
      has recently been rekindled by the description of a largely complete skeleton of
      the adapiform Darwinius, from the middle Eocene of Europe, which has been widely
      publicised as an important 'link' in the early evolution of Anthropoidea. Here we
      describe the complete dentition and jaw of a large-bodied adapiform (Afradapis
      gen. nov.) from the earliest late Eocene of Egypt ( approximately 37 Myr ago)
      that exhibits a striking series of derived dental and gnathic features that also
      occur in younger anthropoid primates-notably the earliest catarrhine ancestors of
      Old World monkeys and apes. Phylogenetic analysis of 360 morphological features
      scored across 117 living and extinct primates (including all candidate stem
      anthropoids) does not place adapiforms as haplorhines (that is, members of a
      Tarsius-Anthropoidea clade) or as stem anthropoids, but rather as sister taxa of
      crown Strepsirrhini; Afradapis and Darwinius are placed in a geographically
      widespread clade of caenopithecine adapiforms that left no known descendants. The
      specialized morphological features that these adapiforms share with anthropoids
      are therefore most parsimoniously interpreted as evolutionary convergences. As
      the largest non-anthropoid primate ever documented in Afro-Arabia, Afradapis
      nevertheless provides surprising new evidence for prosimian diversity in the
      Eocene of Africa, and raises the possibility that ecological competition between
      adapiforms and higher primates might have played an important role during the
      early evolution of stem and crown Anthropoidea in Afro-Arabia.

PMID- 19847264
TI  - Sleep deprivation impairs cAMP signalling in the hippocampus.
AB  - Millions of people regularly obtain insufficient sleep. Given the effect of sleep
      deprivation on our lives, understanding the cellular and molecular pathways
      affected by sleep deprivation is clearly of social and clinical importance. One
      of the major effects of sleep deprivation on the brain is to produce memory
      deficits in learning models that are dependent on the hippocampus. Here we have
      identified a molecular mechanism by which brief sleep deprivation alters
      hippocampal function. Sleep deprivation selectively impaired 3', 5'-cyclic AMP
      (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity in the
      mouse hippocampus, reduced cAMP signalling, and increased activity and protein
      levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of
      mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced
      deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent
      memory. These findings demonstrate that brief sleep deprivation disrupts
      hippocampal function by interfering with cAMP signalling through increased PDE4
      activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic
      approach to counteract the cognitive effects of sleep deprivation.

PMID- 19847265
TI  - The postsynaptic function of type II cochlear afferents.
AB  - The mammalian cochlea is innervated by two classes of sensory neurons. Type I
      neurons make up 90-95% of the cochlear nerve and contact single inner hair cells
      to provide acoustic analysis as we know it. In contrast, the far less numerous
      type II neurons arborize extensively among outer hair cells (OHCs) and supporting
      cells. Their scarcity and smaller calibre axons have made them the subject of
      much speculation, but little experimental progress for the past 50 years. Here we
      record from type II fibres near their terminal arbors under OHCs to show that
      they receive excitatory glutamatergic synaptic input. The type II peripheral
      arbor conducts action potentials, but the small and infrequent glutamatergic
      excitation indicates a requirement for strong acoustic stimulation. Furthermore,
      we show that type II neurons are excited by ATP. Exogenous ATP depolarized type
      II neurons, both directly and by evoking glutamatergic synaptic input. These
      results prove that type II neurons function as cochlear afferents, and can be
      modulated by ATP. The lesser magnitude of synaptic drive dictates a fundamentally
      different role in auditory signalling from that of type I afferents.

PMID- 19847266
TI  - Unexpected consequences of a sudden and massive transposon amplification on rice
      gene expression.
AB  - High-copy-number transposable elements comprise the majority of eukaryotic
      genomes where they are major contributors to gene and genome evolution. However,
      it remains unclear how a host genome can survive a rapid burst of hundreds or
      thousands of insertions because such bursts are exceedingly rare in nature and
      therefore difficult to observe in real time. In a previous study we reported that
      in a few rice strains the DNA transposon mPing was increasing its copy number by
      approximately 40 per plant per generation. Here we exploit the completely
      sequenced rice genome to determine 1,664 insertion sites using high-throughput
      sequencing of 24 individual rice plants and assess the impact of insertion on the
      expression of 710 genes by comparative microarray analysis. We find that the vast
      majority of transposable element insertions either upregulate or have no
      detectable effect on gene transcription. This modest impact reflects a surprising
      avoidance of exon insertions by mPing and a preference for insertion into 5'
      flanking sequences of genes. Furthermore, we document the generation of new
      regulatory networks by a subset of mPing insertions that render adjacent genes
      stress inducible. As such, this study provides evidence for models first proposed
      previously for the involvement of transposable elements and other repetitive
      sequences in genome restructuring and gene regulation.

PMID- 19847267
TI  - A transposon-induced epigenetic change leads to sex determination in melon.
AB  - Sex determination in plants leads to the development of unisexual flowers from an
      originally bisexual floral meristem. This mechanism results in the enhancement of
      outcrossing and promotes genetic variability, the consequences of which are
      advantageous to the evolution of a species. In melon, sexual forms are controlled
      by identity of the alleles at the andromonoecious (a) and gynoecious (g) loci. We
      previously showed that the a gene encodes an ethylene biosynthesis enzyme, CmACS
      7, that represses stamen development in female flowers. Here we show that the
      transition from male to female flowers in gynoecious lines results from
      epigenetic changes in the promoter of a transcription factor, CmWIP1. This
      natural and heritable epigenetic change resulted from the insertion of a
      transposon, which is required for initiation and maintenance of the spreading of
      DNA methylation to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel
      abortion, resulting in the development of unisexual male flowers. Moreover, we
      show that CmWIP1 indirectly represses the expression of the andromonoecious gene,
      CmACS-7, to allow stamen development. Together our data indicate a model in which
      CmACS-7 and CmWIP1 interact to control the development of male, female and
      hermaphrodite flowers in melon.

PMID- 19847268
TI  - Structural basis for biosynthetic programming of fungal aromatic polyketide
      cyclization.
AB  - Polyketides are a class of natural products with diverse structures and
      biological activities. The structural variability of aromatic products of fungal
      nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs)
      results from regiospecific cyclizations of reactive poly-beta-keto intermediates.
      How poly-beta-keto species are synthesized and stabilized, how their chain
      lengths are determined, and, in particular, how specific cyclization patterns are
      controlled have been largely inaccessible and functionally unknown until
      recently. A product template (PT) domain is responsible for controlling specific
      aldol cyclization and aromatization of these mature polyketide precursors, but
      the mechanistic basis is unknown. Here we present the 1.8 A crystal structure and
      mutational studies of a dissected PT monodomain from PksA, the NR-PKS that
      initiates the biosynthesis of the potent hepatocarcinogen aflatoxin B(1) in
      Aspergillus parasiticus. Despite having minimal sequence similarity to known
      enzymes, the structure displays a distinct 'double hot dog' (DHD) fold. Co
      crystal structures with palmitate or a bicyclic substrate mimic illustrate that
      PT can bind both linear and bicyclic polyketides. Docking and mutagenesis studies
      reveal residues important for substrate binding and catalysis, and identify a
      phosphopantetheine localization channel and a deep two-part interior binding
      pocket and reaction chamber. Sequence similarity and extensive conservation of
      active site residues in PT domains suggest that the mechanistic insights gleaned
      from these studies will prove general for this class of IPKSs, and lay a
      foundation for defining the molecular rules controlling NR-PKS cyclization
      specificity.

PMID- 19847270
TI  - Neural circuits: Putting neurons on the map.

PMID- 19847269
TI  - Structural basis for translational fidelity ensured by transfer RNA lysidine
      synthetase.
AB  - Maturation of precursor transfer RNA (pre-tRNA) includes excision of the 5'
      leader and 3' trailer sequences, removal of introns and addition of the CCA
      terminus. Nucleotide modifications are incorporated at different stages of tRNA
      processing, after the RNA molecule adopts the proper conformation. In bacteria,
      tRNA(Ile2) lysidine synthetase (TilS) modifies cytidine into lysidine (L; 2-lysyl
      cytidine) at the first anticodon of tRNA(Ile2) (refs 4-9). This modification
      switches tRNA(Ile2) from a methionine-specific to an isoleucine-specific tRNA.
      However, the aminoacylation of tRNA(Ile2) by methionyl-tRNA synthetase (MetRS),
      before the modification by TilS, might lead to the misincorporation of methionine
      in response to isoleucine codons. The mechanism used by bacteria to avoid this
      pitfall is unknown. Here we show that the TilS enzyme specifically recognizes and
      modifies tRNA(Ile2) in its precursor form, thereby avoiding translation errors.
      We identified the lysidine modification in pre-tRNA(Ile2) isolated from RNase-E
      deficient Escherichia coli and did not detect mature tRNA(Ile2) lacking this
      modification. Our kinetic analyses revealed that TilS can modify both types of
      RNA molecule with comparable efficiencies. X-ray crystallography and mutational
      analyses revealed that TilS specifically recognizes the entire L-shape structure
      in pre-tRNA(Ile2) through extensive interactions coupled with sequential domain
      movements. Our results demonstrate how TilS prevents the recognition of
      tRNA(Ile2) by MetRS and achieves high specificity for its substrate. These two
      key points form the basis for maintaining the fidelity of isoleucine codon
      translation in bacteria. Our findings also provide a rationale for the necessity
      of incorporating specific modifications at the precursor level during tRNA
      biogenesis.

PMID- 19847273
TI  - Jean B Dausset, 19 October 1916-6 June 2009.

PMID- 19847276
TI  - Using the computed tomography in comparison to the orthogonal radiography based
      treatment planning in high dose rate (HDR) brachytherapy in cervical uteri cancer
      patients; a single institution feasibility study.
AB  - INTRODUCTION: Brachytherapy is an integral part in the treatment of cervical
      uteri cancer patients. Orthogonal treatment planning is the standard mode of
      calculation based on reference points. Introduction of the innovative 3-D
      computer based treatment planning allows accurate calculation based on volumetric
      information as regards the target volume and organs at risk (OAR). Also provide
      dose volume histogram (DVH) for proper estimation of the dose in relation to the
      volume. AIM: To correlate and compare the information obtained from the two
      approaches for high dose rate brachytherapy of cervical uteri cancer; the
      orthogonal conventional method and the computerized tomography (CT) three
      dimensions (3D) based calculation method in relation to the target and organ at
      risk (OAR). METHODS: From 6 patients of cervical uteri cancer, 21 applications
      with orthogonal planning using the Brachy Vision treatment planning system
      version 7.3.10 were performed. In 10 applications; comparison between orthogonal
      and CT based planning was done. In orthogonal planning; the dose to point A,
      rectum and bladder were defined according to the American Brachytherapy Society
      (ABS) recommendation. From the CT based planning the target volume and dose
      volume histogram lpar;DVH) were calculated for the clinical target volume (CTV),
      rectum and bladder. From these two sets, information was obtained and compared
      and mean values were derived. RESULTS: For dose prescription at point A, an
      average of 63.5% of CTV received the prescribed dose. The mean ICRU dose to the
      bladder point is 2.9 Gy+/-1.2 SD (Standard Deviation) and 17% of the bladder
      volume derived from CT was encompassed by 2.9 Gy isodose line. The mean ICRU dose
      at the rectum point is 3.4 Gy+/-1.2 SD and 21% of the rectum volume from CT was
      encompassed by 3.4 Gy isodose line. The maximum dose to the rectum and the
      bladder derived from the CT and compared to the maximal dose at ICRU is 1.7 and
      2.8 times higher than the orthogonal reference points; with the corresponding p
      value of (p=0.53 and p=0.005) for the rectum and the bladder respectively.
      CONCLUSIONS: CT based treatment planning for HDR brachytherapy of cervical uteri
      cancer is reliable and more accurate in definition and calculation of the dose to
      the target as well as the critical organs. It allows dose calculation based on
      the actual volume rather than points or bony landmarks.

PMID- 19847277
TI  - Prospective phase II study of brachytherapy boost as a component of neo-adjuvant
      chemotherapy and external beam radiation therapy in locally advanced rectal
      cancer.
AB  - PURPOSE: The aim of the current study is to assess the response rate and toxicity
      profile in patients with locally advanced rectal cancer using brachytherapy (BT)
      boost following external beam radiotherapy (EBRT), concomitant with chemotherapy
      as a component of the neoadjuvant treatment. PATIENTS AND METHODS: This is a
      prospective phase II study of neoadjuvant chemo-radiation therapy for patients
      with locally advanced rectal cancer who presented to the department of radiation
      oncology, King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia.
      Seventeen patients had been included in the study. Radiation therapy was given
      as: phase I, 45 Gy/25 fractions/5 weeks of EBRT, followed by brachytherapy boost
      (within one week after the end of EBRT) using high dose rate iridium 192 (Ir192)
      aiming at 800 cGy given in 2 fractions (each 400 cGy) separated by 1 week. All
      patients received the same concomitant chemotherapy in the form of Capecitabine
      and Oxaliplatin. The clinical and pathological response rates, together with the
      toxicity profile were assessed. RESULTS: Seventeen patients had been studied; the
      majority (14; 82%) were males, while 3 only (18%) were females, their mean age
      was 57.4 years. All patients had low anterior resection (LAR). The clinical
      response rate, assessed by digital rectal examination+/-endoscopy examination 4
      weeks after the end of EBRT and BT, revealed that complete clinical response
      (cCR) was noted in 3 patients (18%), clinical partial response (cPR) in 14
      patients (82%); while the pathological response rate was: complete pathological
      response (pCR) in 8 patients (47%), pathological partial response (pPR) in 9
      patients (53%). The toxicity profile showed that grade III radiation proctitis
      was seen in one patient (6%), grade III dermatitis in 2 (12%), while no patients
      developed grade III cystitis. For chemotherapy toxicities, three patients (18%)
      developed grade III nausea and/or vomiting, 2 (12%) developed grade III diarrhea.
      CONCLUSION: The use of high dose rate brachytherapy as a boost in the neoadjuvant
      chemotherapy and radiation therapy setting in locally advanced rectal cancer is
      an acceptable modality with an appreciable clinical and pathological response
      rates as well as an acceptable toxicity profile.

PMID- 19847278
TI  - Evaluation of bone marrow in 143 lymphomas: the relative frequency and pattern of
      involvement, secondary myelopathies, pitfalls and diagnostic validity.
AB  - The aim of the present study is to assess the frequency of bone marrow (BM)
      involvement by both bone marrow aspirate and biopsy (BMA and BMB, respectively)
      procedures in established cases of lymphomas at initial presentation, and to
      study the relative frequency of marrow disease in relation to lymphoma types,
      patterns of infiltration and the 2ry associated changes, as well as the
      diagnostic challenges. Moreover, the diagnostic validity of BMA is tested taking
      the results of the BMB as the true test results, in order to determine the role
      of each procedure in the diagnostic approach of marrow infiltration. PATIENTS AND
      METHOD: This is a retrospective study carried out on 143 nonconsecutive Egyptian
      patients with lymphomas obtained from a private series during the years 2005 to
      2008. Criteria of inclusion included the availability of full medical records and
      material (medical and pathological), patient consent, nodal disease with no
      therapy prior to BM sampling, except in 7 patients who had another 2nd BMB
      following therapy. BMA and BMB were performed as part of the routine workup for
      diagnosis and staging of lymphoma. The patients had a male to female sex ratio of
      2.6:1 and a wide age range from 4 to 74 years. RESULTS: In the present series, 64
      cases out of the 143 lymphoma patients studied (44.8%) had a BM disease.
      Involvement was mostly bilateral (80%). Patients older than 40 years showed
      higher incidence of bone marrow involvement. There was complete concordance
      (100%) between both diagnostic procedures in the detection of 76 marrow disease
      free lymphoma patients. BMA showed no false positive results and a low rate of
      deference that makes of it an ideal screening test. Three deferred smears of CLL
      for BMB diagnosis were all positive for involvement. However, in a total number
      of 64 BMB positive patients, aspirates could only identify lymphoma involvement
      in 42 lymphoma patients and missed 22 patients with a BM disease, with an overall
      sensitivity rate of 65.6%. BMB had a high diagnostic viability and is an easily
      applied reproducible procedure for diagnosis of BM involvement based on a more
      detailed informative analysis of both architectural and individual
      cytomorphologic changes. CONCLUSION: The relatively high level of BM involvement
      in Egyptian lymphoma patients was directly proportional to high-risk factors. The
      diagnostic validity of BMB is higher than that of BMA. However, BMA serves as a
      good positive test in screening lymphomas for marrow disease. A negative BMA does
      not exclude involvement. Thus, smears should be taken as a complimentary
      procedure.

PMID- 19847279
TI  - Palliative spleen irradiation: can we standardize its technique?
AB  - PURPOSE: To explore the pattern of practice of palliative splenic irradiation
      (PSI) at the National Cancer Institute (NCI), Cairo University. PATIENTS AND
      METHODS: The medical records of patients referred for PSI during the time period
      from 1990 to 2005 were retrospectively reviewed. We compared the three most
      common planning techniques (two parallel opposing, single direct field, anterior
      and lateral fields). RESULTS: Eighteen patients who received PSI were identified.
      Thirteen patients were diagnosed as CML and 5 as CLL. The mean age of the
      patients was 44 (+/-16) years and the majority were men (60%). Spleen enlargement
      was documented in all cases. The single direct anterior field was the most
      commonly used technique. The dose per fraction ranged from 25 cGy to 100 cGy. The
      total dose ranged from 125 cGy to 1200 cGy and the median was 200 cGy (mean 327
      cGy). There was no significant difference between CML and CLL patients regarding
      the dose level. Three out of 5 CLL patients and only one out of 13 CML patients
      received re-irradiation. All patients showed subjective improvement regarding
      pain and swelling. There was a significant increase in the hemoglobin level and a
      significant decrease in the WBC count. The single direct field shows variations
      in the dose from 56 to 102%; however, it is the simplest and the best regarding
      the dose to the surrounding normal tissues especially the kidney and the liver.
      CONCLUSION: PSI has a significant palliative benefit. Although the most widely
      accepted technique is the 2 parallel opposing anterior-posterior fields, single
      anterior field is also considered as a suitable option. Higher doses are needed
      for CLL patients compared to CML patients.

PMID- 19847280
TI  - Galectin-3 immunostaining in cytological and histopathological diagnosis of
      thyroid lesions.
AB  - BACKGROUND: Galectin-3 is a human lectin linked to malignant transformation in
      different organs including thyroid gland. We aimed to evaluate the diagnostic
      role of galectin-3 in differentiating benign from malignant thyroid lesions in
      cytological and histological samples. MATERIAL AND METHODS: This study included a
      total of 79 cases; 19 multinodular goiter (MNG), 19 follicular adenoma (FA), 13
      follicular carcinoma (FTC) and 28 papillary carcinoma (PTC). Galectin-3
      immunostaining was applied on histological sections from all the cases
      (retrospective analysis) as well as for the available preoperative FNAC (28
      cases) (prospective analysis). RESULTS: Retrospective analysis: The positivity
      percentage of galectin-3 was 10.5%, 92.3%, 93% for nonmalignant, FTC and PTC
      respectively. According to H score, glaectin-3 immunostaining was significantly
      lowered in FA) 1+/-2.8 as compared to papillary (158.5+/-88.6) and follicular
      carcinoma (150+/-83.9) (p>0.0001). However, there was no statistically
      significant difference between FTC and PTC (p=0.56) or between classic and
      follicular variants of PTC (p=0.51). Sensitivity, specificity, positive and
      negative predictive values for galectin-3 staining were 93%, 89.5%, 90.5% and 92%
      respectively. Prospective analysis: There were five benign, six malignant and 17
      indeterminate cytology cases. Galectin-3 immunostaining was able to detect the
      benign nature of 11/17 indeterminate cytology. Combination of standard
      cytological evaluation with galectin-3 immunostaining markedly improved
      sensitivity (71% versus 85%), specificity (75% versus 94%), positive predictive
      value (83% versus 92%) negative predictive value (60% versus 87.5%) and
      diagnostic accuracy (72% versus 90%). CONCLUSION: We suggest Galectin-3 as a
      supplementary immunostaining in histological diagnosis of difficult thyroid
      follicular lesions and in preoperative evaluation of indeterminate thyroid
      cytology to avoid unnecessary aggressive surgical interference in benign lesions.

PMID- 19847281
TI  - Evaluation of some biochemical markers as prognostic factors in malignant
      lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) is one of the most important malignant diseases
      worldwide. Cytokines may contribute to the clinical and histopathological
      alterations of the disease, while CD44, the lymphocyte homing receptor, is a
      putative determinant of lymphoma dissemination. To assess their value in NHL, the
      levels of TNF-alpha, IL-2 and sCD44 were measured in patients with different
      stages of NHL and the relation between these levels and tumor burden, presence of
      B symptoms and other prognostic criteria of the disease was evaluated. Fifty-two
      patients with NHL before administration of treatment as well as 20 age- and
      gender-matched controls were enrolled in this study. Clinical and laboratory
      assessment was done for the studied patients and the levels of TNF-alpha, IL-2
      and sCD44 were estimated by enzyme immunoassay. Laboratory assessment included
      measurement of Creactive protein (CRP), lactate dehydrogenase (LDH) and albumin.
      LDH and CRP levels were more significantly higher, while albumin level was
      significantly lower among patients with stage IV as compared to that of patients
      with stages I/II or III. The levels of TNF-alpha, IL-2 and sCD44 were
      significantly higher in NHL patients than in controls. The levels of both TNF
      alpha and IL-2 were positively correlated with LDH and CRP and negatively
      correlated with albumin. However, TNF-alpha, but not IL-2, was negatively
      correlated with hemoglobin (HB). The level of sCD44 was negatively correlated
      with both albumin and HB and positively correlated with CRP. There were
      significant positive correlation between the levels of TNF-alpha, IL-2 and sCD44.
      There was a significant association between the levels of both TNF-alpha and
      sCD44 and the presence of B symptoms. In conclusion, the occurrence of B symptoms
      in NHL may be attributed, at least in part, to high level of TNF-alpha. The
      increased levels of TNF-alpha IL-2 and sCD44 are associated with high tumor
      burden and poor prognostic criteria and it is suggest that they can be used as
      prognostic markers in NHL.

PMID- 19847282
TI  - Liposomal daunorubicin (Daunoxome) and polyethylated glycol conjugated
      asparaginase (PEG-ASPA) in children with relapsed and refractory acute
      lymphoblastic leukemia treated on compassionate basis.
AB  - BACKGROUND: Daunoxome (DNX) is an encapsulated form of daunorubicin in liposomal
      vesicles with suggested better pharmacokinetics, pharmacodynamics and lesser
      cardio toxicity than the free form. Polyethyl glycol asparaginase (PEG-ASPA), a
      modified form of L-asparaginase, has better activity and lesser immunogenicity
      than its native molecule. AIM: To evaluate on a compassionate basis, the
      combination of Daunoxome and PEG-ASPA, as regard to efficacy and toxicity, as a
      salvage treatment in refractory/relapsed childhood ALL. METHODS: The combination
      of these 2 drugs were used in 9 multiple relapsed or refractory ALL children on
      the basis of: DNX weekly 100 mg/m2 D1, 8, 15. PEG-ASPA single, 2500IU/m2 dose
      D15. Vinca alkaloids and corticosteroids were associated. RESULTS: Median
      hospital stay was 4 days (0-55). COMPLICATIONS: Neutropenia grade IV n=4, grade
      III infection n=6, grade II cardiac toxicity n=1, grade III allergy, grade III
      hemostasis disorders, thrombosis, n=1 respectively. All patients achieved
      complete remission (CR) except one who died from disease progression. 8 patients
      were subjected to hematopoietic stem cell transplantatation (HSCT). Two patients
      of them are alive and well, 4 died from transplant related causes and 2 from
      disease progression. CONCLUSION: Salvage treatment containing DNX and PEG-ASPA,
      of small sample childhood ALL with very advanced disease, is feasible as regard
      toxicity and response rate allowing to HSCT and possible cure.

PMID- 19847283
TI  - Intra-operative diagnosis of breast mass-lesions: comparison of the validity of
      touch smear preparation and frozen section techniques.
AB  - BACKGROUND: A reliable intra-operative pathological diagnosis is a mandatory
      before proper surgery of breast cancer. So far, The Frozen Section Technique (FS)
      is the standard technique with a relatively high level of validity. However, when
      the special facilities of FS are unavailable, Touch Smears Preparation technique
      (TSP) could be alternatively adopted. OBJECTIVE: Our objective is to compare the
      validity of TSP in the intraoperative diagnosis of breast mass lesions, with that
      of FS technique. An additional aim is to determine the special advantages of both
      techniques. PATIENTS AND METHODS: The study was conducted on 130 breast mass
      lesions, obtained from operable cases, requesting intra-operative diagnosis at
      the Pathology Department at the National Cancer Institute (NCI), Cairo
      University, during the years 2004-2007. The specimens were subjected to the two
      diagnostic techniques, namely: FS and TSP. Then both were examined separately, by
      two different observers. The results were expressed as: positive for malignancy,
      negative for malignancy or deferred diagnosis. The validity of each FS and TSP is
      tested by using the validity statistical formulas and then results of both were
      compared. Paraffin section was the golden standard for the true diagnosis.
      RESULTS: The accuracy of FS was found to be higher than TSP (100%). Thus, a
      sensitivity of 100% and a specificity of 100%. Whereas, TSP had a sensitivity of
      92.99%, a specificity of 93.33% and an overall accuracy of 92.5%. TSP had also a
      negative predictive value of 80% and the positive predictive value was 97.65%.
      The rate of deferred diagnosis was lower in FS (1.5%) than TSP (6.2%).
      CONCLUSIONS: The study concluded that The FS is much superior to TSP in intra
      operative the diagnosis of breast mass. However, when the special FS equipment is
      lacking, TSP could be a reliable alternative provided that an experienced
      cytopathologist is available. Analysis of predictive value rates revealed that a
      positive cytological report is more reliable than a negative one. Moreover, TSP
      could also be an adjuvant to FS.

PMID- 19847284
TI  - The role of surgical management in pediatric germ cell tumors (GCTs), NCI case
      series.
AB  - PURPOSE: To review the experience of a tertiary referral center in pediatric germ
      cell tumors (GCTs) in the last 8 years and to investigate the impact of surgery
      and site of disease on prognosis. PATIENTS AND METHODS: We retrospectively
      analyzed the cases of pediatric germ cell tumors at National Cancer Institute
      over an 8 years period. Data concerning diagnosis, surgery and medical decisions
      were reviewed and analyzed for all patients. A total of 34 children with (GCTS)
      were found, with a mean age, at presentation, of 6.7 years and a follow-up period
      ranging from 3-52 months. One patient with benign GCT was excluded during
      analysis of the results. RESULTS: Among the 34 patients, there were 14 males and
      20 females with mean age of 6.7 years (range: 9 months-15 years), with male to
      female ratio 1:1.4. All patients were symptomatic at presentation, most commonly
      with abdominal swelling (18 patients; 52.9%). Anatomic distribution of GCTs
      according to sex organ involvement was either gonadal in 21 patients (61.8%) or
      extragonadal in 13 patients (38.2%). All patients had surgery either in the form
      of curative resection or biopsy after formal exploration and evidence of
      irresectability. No significant surgical morbidity or mortality were encountered
      in our patients. Yolk sac tumor and malignant teratoma were the commonest
      histologic subtypes in our series. Metastatic disease was encountered in nine out
      of 33 patients (27.2%). Adjuvant chemotherapy was administered in 28 out of 33
      patients (84.8%), following surgery, including all patients with extragonadal
      disease. Our patients were followed-up to 52 months. Twenty-two patients (66.7%)
      had no recurrence while two patients (6.1%) died from disease. Pelvic
      extragonadal site was the worst site regarding resectability. Complete surgical
      resection showed better disease free survival, while those with irresectable
      disease had comparable overall survival while none could be rendered disease free
      with chemotherapy. CONCLUSION: The initial surgical approach to malignant GCTs at
      all sites should be complete resection when possible; the morbidity of extensive
      surgical resection should be weighed carefully against the good tumor control
      with chemotherapy. Surgical staging does not preclude preservation of fertility,
      which should always be considered in this young age. The site of primary disease
      plays a role in the prognosis of pediatric germ cell tumors with the extragonadal
      pelvic tumors being the worst regarding resectability. Good tumor response can be
      achieved with surgery and chemotherapy even for advanced stage and metastatic
      disease.

PMID- 19847285
TI  - Gastrointestinal stromal tumors (GIST) of the stomach: retrospective experience
      with surgical resection at the National Cancer Institute.
AB  - BACKGROUND: Gastric GISTs account for more than half of all gastrointestinal
      stromal tumors and represent less than 5% of all gastric tumors. The peak age for
      harboring GIST of the stomach is around 60 years and a slight male preponderance
      is reported. These tumors are identified by expression of CD117 or CD34 antigen.
      Symptoms at presentation usually include bleeding, abdominal pain or abdominal
      mass. Endoscopically, they typically appear as a submucosal mass with or without
      ulceration and on CT scans an extragastric mass is usually seen. Complete
      surgical resection provides the only chance for cure, with only 1-2 cm free
      margins needed. However, local recurrence and/or metastases supervene in almost
      half the patients treated with surgery alone, even when no gross residual is
      left. Thereby imatinib mesylate was advocated as an adjuvant to surgery, which
      appears to have improved disease-free and overall survival. AIM OF THE WORK: The
      aim of this work was to assess clinico-pathological features of gastrointestinal
      stromal tumors (GIST) of the stomach and to appraise the results of treatment by
      surgery in patients treated at the National Cancer Institute (NCI) of Cairo
      between January 2002 and December 2007. PATIENTS AND METHODS: Nineteen patients
      with histologically and immuno-histochemically proven GIST of the stomach were
      treated by surgery at the NCI during the 6-year study period. Preoperative
      assessment included detailed history, clinical examination, full laboratory
      tests, endoscopy, abdominal ultrasound and CT. General medical assessment
      included chest X-ray, ECG and echocardiography. RESULTS: The patients' age ranged
      from 26 to 77 years with a median of 51 years. Obvious male/female preponderance
      was noticed (68.4% to 31.6%). Tumors were located at the upper 1/3 in 42.1%, at
      the middle 1/3 in 31.6% and at the lower 1/3 in 26.3%. The most common clinical
      presentation was related to bleeding (hematemesis, melena or anaemia) and was
      seen in 63.2%. No tumors were labeled as very low or low risk while there were
      52.6% intermediate risk and 47.4% high risk. Wedge resection was carried out in
      15.8%, partial gastrectomy in 37.8%, total gastrectomy in 5.2%, extended gastric
      resection in 21.1% and only biopsy in 5.2%. Lymphadenectomy was carried out in
      5/19 patients to reveal negative lymph nodes in all five. Complications occurred
      in 73.7% of patients and only 1 case of early postoperative mortality was
      recorded. Two patients were lost to follow-up. The remaining 16 patients were
      followed-up for a period ranging from 6-34 months with a mean of 19.5+/-5.6
      months and they were all alive by the end of the study, 10 were free of disease
      and 6 showed disease recurrence. CONCLUSION: Gastric GIST can present with vague
      and non specific clinical picture. Therefore, thorough clinical and radiological
      evaluation and preoperative endoscopy and biopsy are essential to reach the
      diagnosis and to assess the risk for metastasis. The clinical outcome of these
      tumors is influenced by completeness of tumor extirpation while avoiding tumor
      rupture, and by the tumor malignant potential. Accordingly for tumors with
      adverse factors, multimodal therapy with adjuvant imatinib or one of its
      successors should be considered in order to improve overall and disease-free
      survival.

PMID- 19847286
TI  - Microvascular radial forearm fasciocutaneous free flap for palatomaxillary
      reconstruction following malignant tumor resection.
AB  - PURPOSE: The aim of this study is to report on the patient's quality of life and
      outcomes after reconstruction of palatomaxillary defects by microvascular radial
      forearm fasciocutaneous free flap (RFFF) and dental obturator. MATERIAL AND
      METHODS: During the period between 2005-2007, 10 patients who had palato
      maxillary defects were immediately reconstructed using RFFF to restore
      physiologic oronasal separation. All patients were treated for malignant tumors
      of hard palate or maxilla and all had preservation of orbital floor. Vascular
      anastomoses were done with the facial vessels in the neck. All the patients
      underwent a lateral thigh split-thickness skin graft for closure of the donor
      site. Outcome measurements included post-operative assessment of flap survival
      and healing, speech, swallowing and diet evaluation and quality of life. Dental
      rehabilitation was done 3 months postoperatively for all patients. RESULTS: Flap
      survival was successful in all cases. In the first 2 weeks post operatively, 80%
      of patients had very good swallowing, speech and diet ability in the form of soft
      chewable foods and by the end of 6 months, all patients had very good swallowing
      and speech function and were able to eat all types of foods. Dental
      rehabilitation with obturator was easily applied and the presence of the flap did
      not interfere with its application. The technique improved chewing ability and
      cosmosis. Complications included, small oronasal fistula in 2 patients (20%) who
      required secondary sutures and delayed wound healing of donor site in one
      patient. CONCLUSION: RFFF for soft tissue reconstruction after maxillectomy is a
      reliable technique that provides a definitive physiologic separation between oral
      and nasal cavity. This allows very early improvement of speech and swallowing
      without being totally dependent on obturator. Dental rehabilitation to improve
      chewing and cosmoses can be done easily with minimal home care. Subsequently, the
      quality of life is markedly improved.

PMID- 19847287
TI  - Effects of Salts of the Hofmeister Series on the Hydrogen Bond Network of Water.
AB  - The effect of salts on water behavior has been a topic of interest for many
      years; however, some recent reports have suggested that ions do not influence the
      hydrogen bonding behavior of water. Using an effective two-state hydrogen bonding
      model to interpret the temperature excursion infrared response of the O-H stretch
      of aqueous salt solutions, we show a strong correlation between salt effects on
      water hydrogen bonding and the Hofmeister order. These data clearly show that
      salts do have a measurable impact on the equilibrium hydrogen bonding behavior of
      water and support models which explain Hofmeister effects on the basis of solute
      charge density.

PMID- 19847288
TI  - Antigenic diversity, transmission mechanisms, and the evolution of pathogens.
AB  - Pathogens have evolved diverse strategies to maximize their transmission fitness.
      Here we investigate these strategies for directly transmitted pathogens using
      mathematical models of disease pathogenesis and transmission, modeling fitness as
      a function of within- and between-host pathogen dynamics. The within-host model
      includes realistic constraints on pathogen replication via resource depletion and
      cross-immunity between pathogen strains. We find three distinct types of
      infection emerge as maxima in the fitness landscape, each characterized by
      particular within-host dynamics, host population contact network structure, and
      transmission mode. These three infection types are associated with distinct non
      overlapping ranges of levels of antigenic diversity, and well-defined patterns of
      within-host dynamics and between-host transmissibility. Fitness, quantified by
      the basic reproduction number, also falls within distinct ranges for each
      infection type. Every type is optimal for certain contact structures over a range
      of contact rates. Sexually transmitted infections and childhood diseases are
      identified as exemplar types for low and high contact rates, respectively. This
      work generates a plausible mechanistic hypothesis for the observed tradeoff
      between pathogen transmissibility and antigenic diversity, and shows how
      different classes of pathogens arise evolutionarily as fitness optima for
      different contact network structures and host contact rates.

PMID- 19847289
TI  - Soluble CD36 ectodomain binds negatively charged diacylglycerol ligands and acts
      as a co-receptor for TLR2.
AB  - BACKGROUND: Cluster of differentiation 36 (CD36) is a transmembrane glycoprotein
      involved in many biological processes, such as platelet biology, angiogenesis and
      in the aetiopathology of atherosclerosis and cardiovascular diseases. Toll-like
      receptors (TLRs) are one of the most important receptors of the innate immune
      system. Their main function is the recognition of conserved structure of
      microorganisms. This recognition triggers signaling pathways that activate
      transcription of cytokines and co-stimulatory molecules which participate in the
      generation of an immune response against microbes. In particular, TLR2 has been
      shown to recognize a broad range of ligands. Recently, we showed that CD36 serves
      as a co-receptor for TLR2 and enhances recognition of specific diacylglycerides
      derived from bacteria. METHODOLOGY/ PRINCIPAL FINDINGS: Here, we investigate the
      mechanism by which CD36 contributes to ligand recognition and activation of TLR2
      signaling pathway. We show that the ectodomain of murine CD36 (mCD36ED) directly
      interacts with negatively charged diacylglycerol ligands, which explains the
      specificity and selectivity of CD36 as a TLR2 co-receptor. We also show that
      mCD36ED amplifies the pro-inflammatory response to lipoteichoic acid in
      macrophages of wild-type mice and restores the pro-inflammatory response of
      macrophages from mice deficient in CD36 (oblivious), but not from mice deficient
      in cluster of differentiation 14 (CD14) (heedless). CONCLUSION/ SIGNIFICANCE:
      These data indicate that the CD36 ectodomain is the only relevant domain for
      activation of TLR2 signaling pathway and that CD36 and CD14 have a non-redundant
      role for loading ligands onto TLR2 in the plasma-membrane. The pro-inflammatory
      role of soluble CD36 can be relevant in the activation of the immune response
      against pathogens, as well as in the progression of chronic diseases. Therefore,
      an increased level of soluble forms of CD36, which has been reported to be
      increased in type II diabetic patients, could accelerate atherosclerosis by
      increasing the pro-inflammatory response to diacylglycerol ligands.

PMID- 19847290
TI  - Angiogenesis in differentiated placental multipotent mesenchymal stromal cells is
      dependent on integrin alpha5beta1.
AB  - Human placental multipotent mesenchymal stromal cells (hPMSCs) can be isolated
      from term placenta, but their angiogenic ability and the regulatory pathways
      involved are not known. hPMSCs were shown to express integrins alpha(v),
      alpha(4), alpha(5), beta(1), beta(3), and beta(5) and could be induced to
      differentiate into cells expressing endothelial markers. Increases in cell
      surface integrins alpha(5) and beta(1), but not alpha(4), alpha(v)beta(3), or
      alpha(v)beta(5), accompanied endothelial differentiation. Vascular endothelial
      growth factor-A augmented the effect of fibronectin in enhancing adhesion and
      migration of differentiated hPMSC through integrin alpha(5)beta(1), but not
      alpha(v)beta(3) or alpha(v)beta(5). Formation of capillary-like structures in
      vitro from differentiated cells was inhibited by pre-treatment with function
      blocking antibodies to integrins alpha(5) and beta(1). When hPMSCs were seeded
      onto chick chorioallantoic membranes (CAM), human von Willebrand factor-positive
      cells were observed to engraft in the chick endothelium. CAMs transplanted with
      differentiated hPMSCs had a greater number of vessels containing human cells and
      more incorporated cells per vessel compared to CAMs transplanted with
      undifferentiated hPMSCs, and overall angiogenesis was enhanced more by the
      differentiated cells. Function-blocking antibodies to integrins alpha(5) and
      beta(1) inhibited angiogenesis in the CAM assay. These results suggest that
      differentiated hPMSCs may contribute to blood vessel formation, and this activity
      depends on integrin alpha(5)beta(1).

PMID- 19847291
TI  - Eicosanoid release is increased by membrane destabilization and CFTR inhibition
      in Calu-3 cells.
AB  - The antiinflammatory protein annexin-1 (ANXA1) and the adaptor S100A10 (p11),
      inhibit cytosolic phospholipase A2 (cPLA2alpha) by direct interaction. Since the
      latter is responsible for the cleavage of arachidonic acid at membrane
      phospholipids, all three proteins modulate eicosanoid production. We have
      previously shown the association of ANXA1 expression with that of CFTR, the
      multifactorial protein mutated in cystic fibrosis. This could in part account for
      the abnormal inflammatory status characteristic of this disease. We postulated
      that CFTR participates in the regulation of eicosanoid release by direct
      interaction with a complex containing ANXA1, p11 and cPLA2alpha. We first
      analyzed by plasmon surface resonance the in vitro binding of CFTR to the three
      proteins. A significant interaction between p11 and the NBD1 domain of CFTR was
      found. We observed in Calu-3 cells a rapid and partial redistribution of all four
      proteins in detergent resistant membranes (DRM) induced by TNF-alpha. This was
      concomitant with increased IL-8 synthesis and cPLA2alpha activation, ultimately
      resulting in eicosanoid (PGE2 and LTB4) overproduction. DRM destabilizing agent
      methyl-beta-cyclodextrin induced further cPLA2alpha activation and eicosanoid
      release, but inhibited IL-8 synthesis. We tested in parallel the effect of short
      exposure of cells to CFTR inhibitors Inh172 and Gly-101. Both inhibitors induced
      a rapid increase in eicosanoid production. Longer exposure to Inh172 did not
      increase further eicosanoid release, but inhibited TNF-alpha-induced
      relocalization to DRM. These results show that (i) CFTR may form a complex with
      cPLA2alpha and ANXA1 via interaction with p11, (ii) CFTR inhibition and DRM
      disruption induce eicosanoid synthesis, and (iii) suggest that the putative
      cPLA2/ANXA1/p11/CFTR complex may participate in the modulation of the TNF-alpha
      induced production of eicosanoids, pointing to the importance of membrane
      composition and CFTR function in the regulation of inflammation mediator
      synthesis.

PMID- 19847292
TI  - p53 Amino-terminus region (1-125) stabilizes and restores heat denatured p53 wild
      phenotype.
AB  - BACKGROUND: The intrinsically disordered N-ter domain (NTD) of p53 encompasses
      approximately hundred amino acids that contain a transactivation domain (1-73)
      and a proline-rich domain (64-92) and is responsible for transactivation function
      and apoptosis. It also possesses an auto-inhibitory function as its removal
      results in remarkable reduction in dissociation of p53 from DNA. PRINCIPAL
      FINDINGS/METHODOLOGY: In this report, we have discovered that p53-NTD spanning
      amino acid residues 1-125 (NTD125) interacted with WT p53 and stabilized its wild
      type conformation under physiological and elevated temperatures, both in vitro
      and in cellular systems. NTD125 prevented irreversible thermal aggregation of
      heat denatured p53, enhanced p21-5'-DBS binding and further restored DBS binding
      activity of heat-denatured p53, in vitro, in a dose-dependent manner. In vivo
      ELISA and immunoprecipitation analysis of NTD125-transfected cells revealed that
      NTD125 shifted equilibrium from p53 mutant to wild type under heat stress
      conditions. Further, NTD125 initiated nuclear translocation of cytoplasmic p53 in
      transcriptionally active state in order to activate p53 downstream genes such as
      p21, Bax, PUMA, Noxa and SUMO. CONCLUSION/SIGNIFICANCE: Here, we showed that a
      novel chaperone-like activity resides in p53-N-ter region. This study might have
      significance in understanding the role of p53-NTD in p53 stabilization,
      conformational activation and apoptosis under heat-stress conditions.

PMID- 19847293
TI  - Accurate strand-specific quantification of viral RNA.
AB  - The presence of full-length complements of viral genomic RNA is a hallmark of RNA
      virus replication within an infected cell. As such, methods for detecting and
      measuring specific strands of viral RNA in infected cells and tissues are
      important in the study of RNA viruses. Strand-specific quantitative real-time PCR
      (ssqPCR) assays are increasingly being used for this purpose, but the accuracy of
      these assays depends on the assumption that the amount of cDNA measured during
      the quantitative PCR (qPCR) step accurately reflects amounts of a specific viral
      RNA strand present in the RT reaction. To specifically test this assumption, we
      developed multiple ssqPCR assays for the positive-strand RNA virus o'nyong-nyong
      (ONNV) that were based upon the most prevalent ssqPCR assay design types in the
      literature. We then compared various parameters of the ONNV-specific assays. We
      found that an assay employing standard unmodified virus-specific primers failed
      to discern the difference between cDNAs generated from virus specific primers and
      those generated through false priming. Further, we were unable to accurately
      measure levels of ONNV (-) strand RNA with this assay when higher levels of cDNA
      generated from the (+) strand were present. Taken together, these results suggest
      that assays of this type do not accurately quantify levels of the anti-genomic
      strand present during RNA virus infectious cycles. However, an assay permitting
      the use of a tag-specific primer was able to distinguish cDNAs transcribed from
      ONNV (-) strand RNA from other cDNAs present, thus allowing accurate
      quantification of the anti-genomic strand. We also report the sensitivities of
      two different detection strategies and chemistries, SYBR(R) Green and DNA
      hydrolysis probes, used with our tagged ONNV-specific ssqPCR assays. Finally, we
      describe development, design and validation of ssqPCR assays for chikungunya
      virus (CHIKV), the recent cause of large outbreaks of disease in the Indian Ocean
      region.

PMID- 19847294
TI  - Experimental infection of a North American raptor, American Kestrel (Falco
      sparverius), with highly pathogenic avian influenza virus (H5N1).
AB  - Several species of wild raptors have been found in Eurasia infected with highly
      pathogenic avian influenza virus (HPAIV) subtype H5N1. Should HPAIV (H5N1) reach
      North America in migratory birds, species of raptors are at risk not only from
      environmental exposure, but also from consuming infected birds and carcasses. In
      this study we used American kestrels as a representative species of a North
      American raptor to examine the effects of HPAIV (H5N1) infection in terms of dose
      response, viral shedding, pathology, and survival. Our data showed that kestrels
      are highly susceptible to HPAIV (H5N1). All birds typically died or were
      euthanized due to severe neurologic disease within 4-5 days of inoculation and
      shed significant amounts of virus both orally and cloacally, regardless of dose
      administered. The most consistent microscopic lesions were necrosis in the brain
      and pancreas. This is the first experimental study of HPAIV infection in a North
      American raptor and highlights the potential risks to birds of prey if HPAIV
      (H5N1) is introduced into North America.

PMID- 19847295
TI  - Parallel explicit and implicit control of reaching.
AB  - BACKGROUND: Human movement can be guided automatically (implicit control) or
      attentively (explicit control). Explicit control may be engaged when learning a
      new movement, while implicit control enables simultaneous execution of multiple
      actions. Explicit and implicit control can often be assigned arbitrarily: we can
      simultaneously drive a car and tune the radio, seamlessly allocating implicit or
      explicit control to either action. This flexibility suggests that sensorimotor
      signals, including those that encode spatially overlapping perception and
      behavior, can be accurately segregated to explicit and implicit control
      processes. METHODOLOGY/PRINCIPAL FINDINGS: We tested human subjects' ability to
      segregate sensorimotor signals to parallel control processes by requiring dual
      (explicit and implicit) control of the same reaching movement and testing for
      interference between these processes. Healthy control subjects were able to
      engage dual explicit and implicit motor control without degradation of
      performance compared to explicit or implicit control alone. We then asked whether
      segregation of explicit and implicit motor control can be selectively disrupted
      by studying dual-control performance in subjects with no clinically manifest
      neurologic deficits in the presymptomatic stage of Huntington's disease (HD).
      These subjects performed successfully under either explicit or implicit control
      alone, but were impaired in the dual-control condition. CONCLUSION/SIGNIFICANCE:
      The human nervous system can exert dual control on a single action, and is
      therefore able to accurately segregate sensorimotor signals to explicit and
      implicit control. The impairment observed in the presymptomatic stage of HD
      points to a possible crucial contribution of the striatum to the segregation of
      sensorimotor signals to multiple control processes.

PMID- 19847297
TI  - Comparing artificial neural networks, general linear models and support vector
      machines in building predictive models for small interfering RNAs.
AB  - BACKGROUND: Exogenous short interfering RNAs (siRNAs) induce a gene knockdown
      effect in cells by interacting with naturally occurring RNA processing machinery.
      However not all siRNAs induce this effect equally. Several heterogeneous kinds of
      machine learning techniques and feature sets have been applied to modeling siRNAs
      and their abilities to induce knockdown. There is some growing agreement to which
      techniques produce maximally predictive models and yet there is little consensus
      for methods to compare among predictive models. Also, there are few comparative
      studies that address what the effect of choosing learning technique, feature set
      or cross validation approach has on finding and discriminating among predictive
      models. PRINCIPAL FINDINGS: Three learning techniques were used to develop
      predictive models for effective siRNA sequences including Artificial Neural
      Networks (ANNs), General Linear Models (GLMs) and Support Vector Machines (SVMs).
      Five feature mapping methods were also used to generate models of siRNA
      activities. The 2 factors of learning technique and feature mapping were
      evaluated by complete 3x5 factorial ANOVA. Overall, both learning techniques and
      feature mapping contributed significantly to the observed variance in predictive
      models, but to differing degrees for precision and accuracy as well as across
      different kinds and levels of model cross-validation. CONCLUSIONS: The methods
      presented here provide a robust statistical framework to compare among models
      developed under distinct learning techniques and feature sets for siRNAs. Further
      comparisons among current or future modeling approaches should apply these or
      other suitable statistically equivalent methods to critically evaluate the
      performance of proposed models. ANN and GLM techniques tend to be more sensitive
      to the inclusion of noisy features, but the SVM technique is more robust under
      large numbers of features for measures of model precision and accuracy. Features
      found to result in maximally predictive models are not consistent across learning
      techniques, suggesting care should be taken in the interpretation of feature
      relevance. In the models developed here, there are statistically differentiable
      combinations of learning techniques and feature mapping methods where the SVM
      technique under a specific combination of features significantly outperforms all
      the best combinations of features within the ANN and GLM techniques.

PMID- 19847296
TI  - Deep sequencing of the small RNAs derived from two symptomatic variants of a
      chloroplastic viroid: implications for their genesis and for pathogenesis.
AB  - Northern-blot hybridization and low-scale sequencing have revealed that plants
      infected by viroids, non-protein-coding RNA replicons, accumulate 21-24 nt viroid
      derived small RNAs (vd-sRNAs) similar to the small interfering RNAs, the
      hallmarks of RNA silencing. These results strongly support that viroids are
      elicitors and targets of the RNA silencing machinery of their hosts. Low-scale
      sequencing, however, retrieves partial datasets and may lead to biased
      interpretations. To overcome this restraint we have examined by deep sequencing
      (Solexa-Illumina) and computational approaches the vd-sRNAs accumulating in GF
      305 peach seedlings infected by two molecular variants of Peach latent mosaic
      viroid (PLMVd) inciting peach calico (albinism) and peach mosaic. Our results
      show in both samples multiple PLMVd-sRNAs, with prevalent 21-nt (+) and (-) RNAs
      presenting a biased distribution of their 5' nucleotide, and adopting a hotspot
      profile along the genomic (+) and (-) RNAs. Dicer-like 4 and 2 (DCL4 and DCL2,
      respectively), which act hierarchically in antiviral defense, likely also mediate
      the genesis of the 21- and 22-nt PLMVd-sRNAs. More specifically, because PLMVd
      replicates in plastids wherein RNA silencing has not been reported, DCL4 and DCL2
      should dice the PLMVd genomic RNAs during their cytoplasmic movement or the PLMVd
      dsRNAs generated by a cytoplasmic RNA-dependent RNA polymerase (RDR), like RDR6,
      acting in concert with DCL4 processing. Furthermore, given that vd-sRNAs derived
      from the 12-14-nt insertion containing the pathogenicity determinant of peach
      calico are underrepresented, it is unlikely that symptoms may result from the
      accidental targeting of host mRNAs by vd-sRNAs from this determinant guiding the
      RNA silencing machinery.

PMID- 19847298
TI  - The ADMR receptor mediates the effects of adrenomedullin on pancreatic cancer
      cells and on cells of the tumor microenvironment.
AB  - BACKGROUND: Adrenomedullin (AM) is highly expressed in pancreatic cancer and
      stimulates pancreatic cancer cells leading to increased tumor growth and
      metastasis. The current study examines the role of specific AM receptors on tumor
      and cells resembling the tumor microenvironment (human pancreatic stellate--HPSC,
      human umbilical vein-- HUVEC and mouse lung endothelial cells--MLEC). METHODS AND
      FINDINGS: AM receptors ADMR and CRLR were present in HPSC, HUVEC and MLECs while
      PDAC cells possessed only ADMR receptors as assessed by RT-PCR and western
      blotting. All cell lines expressed and secreted AM as indicated by ELISA. The
      growth of each of the cell lines was stimulated by exogenous AM and inhibited by
      the antagonist AMA. AM also stimulated in vitro angiogenesis assessed by polygon
      formation of endothelial cell lines. SiRNA-mediated silencing of ADMR, but not
      CRLR, reduced basal growth of all cells examined and reduced polygon formation of
      endothelial cells in vitro. Orthotopic tumors developed with shADMR bearing
      cancer cells had dramatically reduced primary tumor volume (>90%) and lung and
      liver metastasis compared to shControl bearing cells. To validate ADMR as a
      potential therapeutic target, in vivo studies were conducted using neutral
      nanoliposomes to systemically deliver human siRNA to ADMR to silence human cancer
      cells and mouse siRNA to ADMR to silence mouse tumor stromal cells. Systemic
      silencing of both human and mouse ADMR had no obvious adverse effects but
      strongly reduced tumor development. CONCLUSION: ADMR mediates the stimulatory
      effects of AM on cancer cells and on endothelial and stellate cells within the
      tumor microenvironment. These data support the further development of ADMR as a
      useful target treatment of pancreatic cancer.

PMID- 19847299
TI  - Accounting for redundancy when integrating gene interaction databases.
AB  - During the last years gene interaction networks are increasingly being used for
      the assessment and interpretation of biological measurements. Knowledge of the
      interaction partners of an unknown protein allows scientists to understand the
      complex relationships between genetic products, helps to reveal unknown
      biological functions and pathways, and get a more detailed picture of an
      organism's complexity. Being able to measure all protein interactions under all
      relevant conditions is virtually impossible. Hence, computational methods
      integrating different datasets for predicting gene interactions are needed.
      However, when integrating different sources one has to account for the fact that
      some parts of the information may be redundant, which may lead to an
      overestimation of the true likelihood of an interaction. Our method integrates
      information derived from three different databases (Bioverse, HiMAP and STRING)
      for predicting human gene interactions. A Bayesian approach was implemented in
      order to integrate the different data sources on a common quantitative scale. An
      important assumption of the Bayesian integration is independence of the input
      data (features). Our study shows that the conditional dependency cannot be
      ignored when combining gene interaction databases that rely on partially
      overlapping input data. In addition, we show how the correlation structure
      between the databases can be detected and we propose a linear model to correct
      for this bias. Benchmarking the results against two independent reference data
      sets shows that the integrated model outperforms the individual datasets. Our
      method provides an intuitive strategy for weighting the different features while
      accounting for their conditional dependencies.

PMID- 19847300
TI  - Fast and flexible selection with a single switch.
AB  - Selection methods that require only a single-switch input, such as a button click
      or blink, are potentially useful for individuals with motor impairments, mobile
      technology users, and individuals wishing to transmit information securely. We
      present a single-switch selection method, "Nomon," that is general and efficient.
      Existing single-switch selection methods require selectable options to be
      arranged in ways that limit potential applications. By contrast, traditional
      operating systems, web browsers, and free-form applications (such as drawing)
      place options at arbitrary points on the screen. Nomon, however, has the
      flexibility to select any point on a screen. Nomon adapts automatically to an
      individual's clicking ability; it allows a person who clicks precisely to make a
      selection quickly and allows a person who clicks imprecisely more time to make a
      selection without error. Nomon reaps gains in information rate by allowing the
      specification of beliefs (priors) about option selection probabilities and by
      avoiding tree-based selection schemes in favor of direct (posterior) inference.
      We have developed both a Nomon-based writing application and a drawing
      application. To evaluate Nomon's performance, we compared the writing application
      with a popular existing method for single-switch writing (row-column scanning).
      Novice users wrote 35% faster with the Nomon interface than with the scanning
      interface. An experienced user (author TB, with 10 hours practice) wrote at
      speeds of 9.3 words per minute with Nomon, using 1.2 clicks per character and
      making no errors in the final text.

PMID- 19847301
TI  - Bright field microscopy as an alternative to whole cell fluorescence in automated
      analysis of macrophage images.
AB  - BACKGROUND: Fluorescence microscopy is the standard tool for detection and
      analysis of cellular phenomena. This technique, however, has a number of
      drawbacks such as the limited number of available fluorescent channels in
      microscopes, overlapping excitation and emission spectra of the stains, and
      phototoxicity. METHODOLOGY: We here present and validate a method to
      automatically detect cell population outlines directly from bright field images.
      By imaging samples with several focus levels forming a bright field -stack, and
      by measuring the intensity variations of this stack over the -dimension, we
      construct a new two dimensional projection image of increased contrast. With
      additional information for locations of each cell, such as stained nuclei, this
      bright field projection image can be used instead of whole cell fluorescence to
      locate borders of individual cells, separating touching cells, and enabling
      single cell analysis. Using the popular CellProfiler freeware cell image analysis
      software mainly targeted for fluorescence microscopy, we validate our method by
      automatically segmenting low contrast and rather complex shaped murine macrophage
      cells. SIGNIFICANCE: The proposed approach frees up a fluorescence channel, which
      can be used for subcellular studies. It also facilitates cell shape measurement
      in experiments where whole cell fluorescent staining is either not available, or
      is dependent on a particular experimental condition. We show that whole cell area
      detection results using our projected bright field images match closely to the
      standard approach where cell areas are localized using fluorescence, and conclude
      that the high contrast bright field projection image can directly replace one
      fluorescent channel in whole cell quantification. Matlab code for calculating the
      projections can be downloaded from the supplementary site:
      http://sites.google.com/site/brightfieldorstaining.

PMID- 19847302
TI  - A new paradigm for MAPK: structural interactions of hERK1 with mitochondria in
      HeLa cells.
AB  - Extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) are members of the
      MAPK family and participate in the transduction of stimuli in cellular responses.
      Their long-term actions are accomplished by promoting the expression of specific
      genes whereas faster responses are achieved by direct phosphorylation of
      downstream effectors located throughout the cell. In this study we determined
      that hERK1 translocates to the mitochondria of HeLa cells upon a proliferative
      stimulus. In the mitochondrial environment, hERK1 physically associates with (i)
      at least 5 mitochondrial proteins with functions related to transport (i.e.
      VDAC1), signalling, and metabolism; (ii) histones H2A and H4; and (iii) other
      cytosolic proteins. This work indicates for the first time the presence of
      diverse ERK-complexes in mitochondria and thus provides a new perspective for
      assessing the functions of ERK1 in the regulation of cellular signalling and
      trafficking in HeLa cells.

PMID- 19847303
TI  - Anemia of inflammation is related to cognitive impairment among children in
      Leyte, the Philippines.
AB  - BACKGROUND: Many studies have addressed the relationship between iron deficiency
      anemia (IDA) and cognitive impairment, but none have evaluated the role of non
      iron deficiency anemia (NIDA). One of the main causes of NIDA in developing
      countries is AI, largely due to infectious diseases, whereby iron is shunted away
      from bio-available forms to storage forms, making it less accessible for use by
      host tissues. The objective of this study was to determine the effect of NIDA,
      due largely to AI in this context, on cognitive function after adjustment for
      potential confounders. METHODOLOGY: This cross-sectional study was conducted in
      Leyte, The Philippines among 322 children ages 7-18 years. Blood samples were
      collected and analyzed at the time of cognition testing. Three stool samples were
      collected and evaluated by the Kato Katz method for quantitative assessment for
      Schistosoma japonicum and geo-helminth infection. Socio-economic status (SES) was
      evaluated by survey. Linear regression models were used to quantify the adjusted
      relationship between performance in different cognitive domains and both IDA and
      NIDA. PRINCIPAL FINDINGS: After adjusting for age, sex, SES and nutritional
      status, children in the NIDA had lower scores on the PNIT (P = <0.05) and the
      WRAML memory domain (P<0.05) compared to children in the non-anemic group.
      Children in the IDA had lower performance on the PNIT compared to the non-anemic
      group after controlling for potential confounders (P<0.05). CONCLUSIONS: NIDA,
      predominantly due to AI in this context, was related to lower performance on two
      tests of cognitive function. This is likely due to decreased delivery of iron to
      host tissues in this context, including the CNS.

PMID- 19847304
TI  - Assessment of metabolome annotation quality: a method for evaluating the false
      discovery rate of elemental composition searches.
AB  - BACKGROUND: In metabolomics researches using mass spectrometry (MS), systematic
      searching of high-resolution mass data against compound databases is often the
      first step of metabolite annotation to determine elemental compositions
      possessing similar theoretical mass numbers. However, incorrect hits derived from
      errors in mass analyses will be included in the results of elemental composition
      searches. To assess the quality of peak annotation information, a novel
      methodology for false discovery rates (FDR) evaluation is presented in this
      study. Based on the FDR analyses, several aspects of an elemental composition
      search, including setting a threshold, estimating FDR, and the types of elemental
      composition databases most reliable for searching are discussed.
      METHODOLOGY/PRINCIPAL FINDINGS: The FDR can be determined from one measured value
      (i.e., the hit rate for search queries) and four parameters determined by Monte
      Carlo simulation. The results indicate that relatively high FDR values (30-50%)
      were obtained when searching time-of-flight (TOF)/MS data using the KNApSAcK and
      KEGG databases. In addition, searches against large all-in-one databases (e.g.,
      PubChem) always produced unacceptable results (FDR >70%). The estimated FDRs
      suggest that the quality of search results can be improved not only by performing
      more accurate mass analysis but also by modifying the properties of the compound
      database. A theoretical analysis indicates that FDR could be improved by using
      compound database with smaller but higher completeness entries.
      CONCLUSIONS/SIGNIFICANCE: High accuracy mass analysis, such as Fourier transform
      (FT)-MS, is needed for reliable annotation (FDR <10%). In addition, a small,
      customized compound database is preferable for high-quality annotation of
      metabolome data.

PMID- 19847305
TI  - Variation at GRN 3'-UTR rs5848 is not associated with a risk of frontotemporal
      lobar degeneration in Dutch population.
AB  - BACKGROUND: A single nucleotide polymorphism (rs5848) located in the 3'-
      untranslated region of GRN has recently been associated with a risk of
      frontotemporal lobar degeneration (FTLD) in North American population
      particularly in pathologically confirmed cases with neural inclusions
      immunoreactive for ubiquitin and TAR DNA-binding protein 43 (TDP-43), but
      negative for tau and alpha-synuclein (FTLD-TDP). METHODOLOGY/PRINCIPAL FINDINGS:
      In an effort to replicate these results in a different population, rs5848 was
      genotyped in 256 FTLD cases and 1695 controls from the Netherlands. Single SNP
      gender-adjusted logistic regression analysis revealed no significant association
      between variation at rs5848 and FTLD. Fisher's exact test, failed to find any
      significant association between rs5848 and a subset of 23 pathology confirmed
      FTLD-TDP cases. CONCLUSIONS/SIGNIFICANCE: The evidence presented here suggests
      that variation at rs5848 does not contribute to the etiology of FTLD in the Dutch
      population.

PMID- 19847306
TI  - Single nucleotide polymorphism analysis of European archaeological M. leprae DNA.
AB  - BACKGROUND: Leprosy was common in Europe eight to twelve centuries ago but
      molecular confirmation of this has been lacking. We have extracted M. leprae
      ancient DNA (aDNA) from medieval bones and single nucleotide polymorphism (SNP)
      typed the DNA, this provides insight into the pattern of leprosy transmission in
      Europe and may assist in the understanding of M. leprae evolution. METHODS AND
      FINDINGS: Skeletons have been exhumed from 3 European countries (the United
      Kingdom, Denmark and Croatia) and are dated around the medieval period (476 to
      1350 A.D.). we tested for the presence of 3 previously identified single
      nucleotide polymorphisms (SNPs) in 10 aDNA extractions. M. leprae aDNA was
      extracted from 6 of the 10 bone samples. SNP analysis of these 6 extractions were
      compared to previously analysed European SNP data using the same PCR assays and
      were found to be the same. Testing for the presence of SNPs in M. leprae DNA
      extracted from ancient bone samples is a novel approach to analysing European M.
      leprae DNA and the findings concur with the previously published data that
      European M. leprae strains fall in to one group (SNP group 3). CONCLUSIONS: These
      findings support the suggestion that the M. leprae genome is extremely stable and
      show that archaeological M. leprae DNA can be analysed to gain detailed
      information about the genotypic make-up of European leprosy, which may assist in
      the understanding of leprosy transmission worldwide.

PMID- 19847307
TI  - Metabolomic profiling in LRRK2-related Parkinson's disease.
AB  - BACKGROUND: Mutations in LRRK2 gene represent the most common known genetic cause
      of Parkinson's disease (PD). METHODOLOGY/PRINCIPAL FINDINGS: We used metabolomic
      profiling to identify biomarkers that are associated with idiopathic and LRRK2
      PD. We compared plasma metabolomic profiles of patients with PD due to the G2019S
      LRRK2 mutation, to asymptomatic family members of these patients either with or
      without G2019S LRRK2 mutations, and to patients with idiopathic PD, as well as
      non-related control subjects. We found that metabolomic profiles of both
      idiopathic PD and LRRK2 PD subjects were clearly separated from controls. LRRK2
      PD patients had metabolomic profiles distinguishable from those with idiopathic
      PD, and the profiles could predict whether the PD was secondary to LRRK2
      mutations or idiopathic. Metabolomic profiles of LRRK2 PD patients were well
      separated from their family members, but there was a slight overlap between
      family members with and without LRRK2 mutations. Both LRRK2 and idiopathic PD
      patients showed significantly reduced uric acid levels. We also found a
      significant decrease in levels of hypoxanthine and in the ratios of major
      metabolites of the purine pathway in plasma of PD patients.
      CONCLUSIONS/SIGNIFICANCE: These findings show that LRRK2 patients with the G2019S
      mutation have unique metabolomic profiles that distinguish them from patients
      with idiopathic PD. Furthermore, asymptomatic LRRK2 carriers can be separated
      from gene negative family members, which raises the possibility that metabolomic
      profiles could be useful in predicting which LRRK2 carriers will eventually
      develop PD. The results also suggest that there are aberrations in the purine
      pathway in PD which may occur upstream from uric acid.

PMID- 19847308
TI  - Hypoxia transiently sequesters mps1 and polo to collagenase-sensitive filaments
      in Drosophila prometaphase oocytes.
AB  - BACKGROUND: The protein kinases Mps1 and Polo, which are required for proper cell
      cycle regulation in meiosis and mitosis, localize to numerous ooplasmic filaments
      during prometaphase in Drosophila oocytes. These filaments first appear
      throughout the oocyte at the end of prophase and are disassembled after egg
      activation. METHODOLOGY/PRINCIPAL FINDINGS: We showed here that Mps1 and Polo
      proteins undergo dynamic and reversible localization to static ooplasmic
      filaments as part of an oocyte-specific response to hypoxia. The observation that
      Mps1- and Polo-associated filaments reappear in the same locations through
      multiple cycles of oxygen deprivation demonstrates that underlying structural
      components of the filaments must still be present during normoxic conditions.
      Using immuno-electron microscopy, we observed triple-helical binding of Mps1 to
      numerous electron-dense filaments, with the gold label wrapped around the outside
      of the filaments like a garland. In addition, we showed that in live oocytes the
      relocalization of Mps1 and Polo to filaments is sensitive to injection of
      collagenase, suggesting that the structural components of the filaments are
      composed of collagen-like fibrils. However, the collagen-like genes we have been
      able to test so far (vkg and CG42453) did not appear to be associated with the
      filaments, demonstrating that the collagenase-sensitive component of the
      filaments is one of a number of other Drosophila proteins bearing a collagenase
      cleavage site. Finally, as hypoxia is known to cause Mps1 protein to accumulate
      at kinetochores in syncytial embryos, we also show that GFP-Polo accumulates at
      both kinetochores and centrosomes in hypoxic syncytial embryos.
      CONCLUSIONS/SIGNIFICANCE: These findings identify both a novel cellular structure
      (the ooplasmic filaments) as well as a new localization pattern for Mps1 and Polo
      and demonstrate that hypoxia affects Polo localization in Drosophila.

PMID- 19847309
TI  - Heritability and demographic analyses in the large isolated population of Val
      Borbera suggest advantages in mapping complex traits genes.
AB  - BACKGROUND: Isolated populations are a useful resource for mapping complex traits
      due to shared stable environment, reduced genetic complexity and extended Linkage
      Disequilibrium (LD) compared to the general population. Here we describe a large
      genetic isolate from the North West Apennines, the mountain range that runs
      through Italy from the North West Alps to the South. METHODOLOGY/PRINCIPAL
      FINDINGS: The study involved 1,803 people living in 7 villages of the upper
      Borbera Valley. For this large population cohort, data from genealogy
      reconstruction, medical questionnaires, blood, anthropometric and bone status QUS
      parameters were evaluated. Demographic and epidemiological analyses indicated a
      substantial genetic component contributing to each trait variation as well as
      overlapping genetic determinants and family clustering for some traits.
      CONCLUSIONS/SIGNIFICANCE: The data provide evidence for significant heritability
      of medical relevant traits that will be important in mapping quantitative traits.
      We suggest that this population isolate is suitable to identify rare variants
      associated with complex phenotypes that may be difficult to study in larger but
      more heterogeneous populations.

PMID- 19847310
TI  - An eight-gene blood expression profile predicts the response to infliximab in
      rheumatoid arthritis.
AB  - BACKGROUND: TNF alpha blockade agents like infliximab are actually the treatment
      of choice for those rheumatoid arthritis (RA) patients who fail standard therapy.
      However, a considerable percentage of anti-TNF alpha treated patients do not show
      a significant clinical response. Given that new therapies for treatment of RA
      have been recently approved, there is a pressing need to find a system that
      reliably predicts treatment response. We hypothesized that the analysis of whole
      blood gene expression profiles of RA patients could be used to build a robust
      predictor to infliximab therapy. METHODS AND FINDINGS: We performed microarray
      gene expression analysis on whole blood RNA samples from RA patients starting
      infliximab therapy (n = 44). The clinical response to infliximab was determined
      at week 14 using the EULAR criteria. Blood cell populations were determined using
      flow cytometry at baseline, week 2 and week 14 of treatment. Using complete cross
      validation and repeated random sampling we identified a robust 8-gene predictor
      model (96.6% Leave One Out prediction accuracy, P = 0.0001). Applying this model
      to an independent validation set of RA patients, we estimated an 85.7% prediction
      accuracy (75-100%, 95% CI). In parallel, we also observed a significantly higher
      number of CD4+CD25+ cells (i.e. regulatory T cells) in the responder group
      compared to the non responder group at baseline (P = 0.0009). CONCLUSIONS: The
      present 8-gene model obtained from whole blood expression efficiently predicts
      response to infliximab in RA patients. The application of the present system in
      the clinical setting could assist the clinician in the selection of the optimal
      treatment strategy in RA.

PMID- 19847311
TI  - Avoiding negative outcomes: tracking the mechanisms of avoidance learning in
      humans during fear conditioning.
AB  - Previous research across species has shown that the amygdala is critical for
      learning about aversive outcomes, while the striatum is involved in reward
      related processing. Less is known, however, about the role of the amygdala and
      the striatum in learning how to exert control over emotions and avoid negative
      outcomes. One potential mechanism for active avoidance of stressful situations is
      postulated to involve amygdala-striatal interactions. The goal of this study was
      to investigate the physiological and neural correlates underlying avoidance
      learning in humans. Specifically, we used a classical conditioning paradigm where
      three different conditioned stimuli (CS) were presented. One stimulus predicted
      the delivery of a shock upon stimulus offset (CS+), while another predicted no
      negative consequences (CS-). A third conditioned cue also predicted delivery of a
      shock, but participants were instructed that upon seeing this stimulus, they
      could avoid the shock if they chose the correct action (AV+). After successful
      learning, participants could then easily terminate the shock during subsequent
      stimulus presentations (AV-). Physiological responses (as measured by skin
      conductance responses) confirmed a main effect of conditioning, particularly
      showing higher arousal responses during pre (AV+) compared to post (AV-) learning
      of an avoidance response. Consistent with animal models, amygdala-striatal
      interactions were observed to underlie the acquisition of an avoidance response.
      These results support a mechanism of active coping with conditioned fear that
      allows for the control over emotional responses such as fears that can become
      maladaptive and influence our decision-making.

PMID- 19847312
TI  - SGC--structural biology and human health: a new approach to publishing structural
      biology results.

PMID- 19847313
TI  - Memory suppression is an active process that improves over childhood.
AB  - We all have memories that we prefer not to think about. The ability to suppress
      retrieval of unwanted memories has been documented in behavioral and neuroimaging
      research using the Think/No-Think (TNT) paradigm with adults. Attempts to stop
      memory retrieval are associated with increased activation of lateral prefrontal
      cortex (PFC) and concomitant reduced activation in medial temporal lobe (MTL)
      structures. However, the extent to which children have the ability to actively
      suppress their memories is unknown. This study investigated memory suppression in
      middle childhood using the TNT paradigm. Forty children aged 8-12 and 30 young
      adults were instructed either to remember (Think) or suppress (No-Think) the
      memory of the second word of previously studied word-pairs, when presented with
      the first member as a reminder. They then performed two different cued recall
      tasks, testing their memory for the second word in each pair after the TNT phase
      using the same first studied word within the pair as a cue (intra-list cue) and
      also an independent cue (extra-list cue). Children exhibited age-related
      improvements in memory suppression from age 8 to 12 in both memory tests, against
      a backdrop of overall improvements in declarative memory over this age range.
      These findings suggest that memory suppression is an active process that develops
      during late childhood, likely due to an age-related refinement in the ability to
      engage PFC to down-regulate activity in areas involved in episodic retrieval.

PMID- 19847314
TI  - Bio-swarm-pipeline: a light-weight, extensible batch processing system for
      efficient biomedical data processing.
AB  - A streamlined scientific workflow system that can track the details of the data
      processing history is critical for the efficient handling of fundamental routines
      used in scientific research. In the scientific workflow research community, the
      information that describes the details of data processing history is referred to
      as "provenance" which plays an important role in most of the existing workflow
      management systems. Despite its importance, however, provenance modeling and
      management is still a relatively new area in the scientific workflow research
      community. The proper scope, representation, granularity and implementation of a
      provenance model can vary from domain to domain and pose a number of challenges
      for an efficient pipeline design. This paper provides a case study on structured
      provenance modeling and management problems in the neuroimaging domain by
      introducing the Bio-Swarm-Pipeline. This new model, which is evaluated in the
      paper through real world scenarios, systematically addresses the provenance
      scope, representation, granularity, and implementation issues related to the
      neuroimaging domain. Although this model stems from applications in neuroimaging,
      the system can potentially be adapted to a wide range of bio-medical application
      scenarios.

PMID- 19847316
TI  - Ric-8A, a Galpha protein guanine nucleotide exchange factor potentiates taste
      receptor signaling.
AB  - Taste receptors for sweet, bitter and umami tastants are G-protein-coupled
      receptors (GPCRs). While much effort has been devoted to understanding G-protein
      receptor interactions and identifying the components of the signalling cascade
      downstream of these receptors, at the level of the G-protein the modulation of
      receptor signal transduction remains relatively unexplored. In this regard a
      taste-specific regulator of G-protein signaling (RGS), RGS21, has recently been
      identified. To study whether guanine nucleotide exchange factors (GEFs) are
      involved in the transduction of the signal downstream of the taste GPCRs we
      investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their
      interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins
      were initially identified as potent GEFs for a range of Galpha subunits and Ric
      8B has recently been shown to amplify olfactory signal transduction. We find that
      both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and
      that most of these cells contain IP3R-3 a marker for sweet, umami and bitter
      taste receptor cells. Ric-8A interacts with Galpha-gustducin and Galphai2 through
      which it amplifies the signal transduction of hTas2R16, a receptor for bitter
      compounds. Overall, these findings are consistent with a role for Ric-8 in
      mammalian taste signal transduction.

PMID- 19847317
TI  - Hyaluronan-based Glycoclusters as Probes for Chemical Glycobiology.
AB  - A strategy is described for the synthesis of beta-(1,3)-GlcA-GlcNAc dimeric and
      tetrameric glycoclusters through the conjugation of disaccharide groups onto a
      diaminodiamide aromatic scaffold by reductive amination.

PMID- 19847318
TI  - Distributed Computation of the knn Graph for Large High-Dimensional Point Sets.
AB  - High-dimensional problems arising from robot motion planning, biology, data
      mining, and geographic information systems often require the computation of k
      nearest neighbor (knn) graphs. The knn graph of a data set is obtained by
      connecting each point to its k closest points. As the research in the above
      mentioned fields progressively addresses problems of unprecedented complexity,
      the demand for computing knn graphs based on arbitrary distance metrics and large
      high-dimensional data sets increases, exceeding resources available to a single
      machine. In this work we efficiently distribute the computation of knn graphs for
      clusters of processors with message passing. Extensions to our distributed
      framework include the computation of graphs based on other proximity queries,
      such as approximate knn or range queries. Our experiments show nearly linear
      speedup with over one hundred processors and indicate that similar speedup can be
      obtained with several hundred processors.

PMID- 19847319
TI  - Safety and efficacy of undenatured type II collagen in the treatment of
      osteoarthritis of the knee: a clinical trial.
AB  - Previous studies have shown that undenatured type II collagen (UC-II) is
      effective in the treatment of rheumatoid arthritis, and preliminary human and
      animal trials have shown it to be effective in treating osteoarthritis (OA). The
      present clinical trial evaluated the safety and efficacy of UC-II as compared to
      a combination of glucosamine and chondroitin (G+C) in the treatment of OA of the
      knee. The results indicate that UC-II treatment was more efficacious resulting in
      a significant reduction in all assessments from the baseline at 90 days; whereas,
      this effect was not observed in G+C treatment group. Specifically, although both
      treatments reduced the Western Ontario McMaster Osteoarthritis Index (WOMAC)
      score, treatment with UC-II reduced the WOMAC score by 33% as compared to 14% in
      G+C treated group after 90 days. Similar results were obtained for visual analog
      scale (VAS) scores. Although both the treatments reduced the VAS score, UC-II
      treatment decreased VAS score by 40% after 90 days as compared to 15.4% in G+C
      treated group. The Lequesne's functional index was used to determine the effect
      of different treatments on pain during daily activities. Treatment with UC-II
      reduced Lequesne's functional index score by 20% as compared to 6% in G+C treated
      group at the end of 90-day treatment. Thus, UC-II treated subjects showed
      significant enhancement in daily activities suggesting an improvement in their
      quality of life.

PMID- 19847320
TI  - An apoA-I mimetic peptide facilitates off-loading cholesterol from HDL to liver
      cells through scavenger receptor BI.
AB  - Apolipoprotein A-I (apoA-I) mimetic peptides have been pursued as new therapeutic
      agents for the treatment of atherosclerosis, yet their precise mechanism
      responsible for atheroprotection remains unclear. Like apoA-I itself, most of
      these peptides are capable of stimulating cholesterol efflux from macrophages or
      foam cells, and some of them stimulate lecithin cholesterol acyltransferase
      (LCAT) activity in the reverse cholesterol transport (RCT) pathway. However, the
      ability of mimetic peptides to deliver cholesterol into hepatocytes (off
      loading), the last step of the RCT pathway, has not been demonstrated. In this
      study, we compared a mimetic peptide D-4F to purified apoA-I, to address the role
      that mimetics play during the off-loading process. Both D-4F and apoA-I formed
      spherical nano-particles when reconstituted with cholesteryl ester and
      phospholipids. Compared to apoA-I, D-4F particles were 20 times more efficient in
      off-loading cholesterol to HepG2 hepatocytes with an apparent K(t) (transport) of
      0.74 mug/mL. Furthermore, D-4F also facilitated cholesteryl ester offloading from
      HDL particles into HepG2 cells when it was pre-incubated with these HDL
      particles. Using an inducible HEK293 cell line, we demonstrated that these nano
      particles were able to be taken up through SR-BI, a HDL selective receptor.
      Cholesterol uptake by HepG2 cells was completely blocked by a neutralizing
      monoclonal antibody against SR-BI, demonstrating that D-4F particles, similar to
      HDL, specifically off-loaded cholesterol through SR-BI. Overall our data provides
      evidence that D-4F is capable of mimicking apoA-I to form HDL-like particles, and
      off-loads cholesterol for catabolism and excretion, thus completing RCT.

PMID- 19847322
TI  - Karyology of eight species of bats (Mammalia: Chiroptera) from Hainan Island,
      China.
AB  - Karyotypes and chromosomal data are presented for eight bat species representing
      two families (Rhinolophidae and Vespertilionidae) from Hainan Island, China. The
      species investigated were Rhinolophus lepidus (2n = 62, FN = 60), R. pusillus (2n
      = 62, FN = 60), R. affinis (2n = 62, FN = 60), R. sinicus (2n = 36, FN = 60),
      Myotis horsfieldi (2n = 44, FN = 52), Pipistrellus abramus (2n = 26, FN = 44),
      Miniopterus australis (2n = 46, FN = 50) and M. schreibersii (2n = 46, FN = 50).
      The karyotype of Rhinolophus lepidus is reported for the first time.

PMID- 19847321
TI  - Clinical diagnosis for discogenic low back pain.
AB  - Discogenic lower back pain (DLBP) is the most common type of chronic lower back
      pain (LBP), accounting for 39% of cases, compared to 30% of cases due to disc
      herniation, and even lower prevalence rates for other causes, such as
      zygapophysial joint pain. Only a small proportion (approximately 20%) of LBP
      cases can be attributed with reasonable certainty to a pathologic or anatomical
      entity. Thus, diagnosing the cause of LBP represents the biggest challenge for
      doctors in this field. In this review, we summarize the process of obtaining a
      clinical diagnosis of DLBP and discuss the potential for serum-based diagnosis in
      the near future. The use of serum biomarkers to diagnose DLBP is likely to
      increase the ease of diagnosis as well as produce more accurate and reproducible
      results.

PMID- 19847323
TI  - The role of the murine motor cortex in action duration and order.
AB  - This study examined the contributions of the primary and secondary motor cortices
      (M1 and M2) to action differentiation and sequencing in mice. In Experiment 1,
      mice with excitotoxic lesions of M1 and M2 and sham controls learned to emit
      lever presses exceeding a criterion duration to earn food rewards. Duration
      differentiation obeys Weber's law - i.e. the spread of the distribution is
      proportional to the average duration. M1 or M2 lesions did not affect
      differentiation of press durations. Experiment 2 studied the effects of the same
      lesions on the learning of a simple sequence consisting of two lever presses, one
      distal, and the other proximal, to the reward. M2 lesions impaired the
      acquisition and reversal of this sequence. M1 lesions, by contrast, had no effect
      on acquisition but impaired sequence reversal. Moreover, duration of the first
      press in a sequence was on average twice as long as that of the second press,
      though this ratio was not affected by motor cortex lesions. Together these
      results offer a first glimpse into the cortical substrates of instrumental
      differentiation in mice.

PMID- 19847324
TI  - Manipulating executive function with transcranial direct current stimulation.

PMID- 19847325
TI  - Glutathione reductase activity correlates with concentration of extracellular
      matrix degradation products in synovial fluid from patients with joint diseases.
AB  - The mechanisms underlying cartilage matrix degradation in joint diseases is not
      fully understood but reactive oxygen species are implicated as main causative
      factors. Comparative studies of glutathione reductase (GR) activity in synovial
      fluid from patients with rheumatoid arthritis (RA), reactive arthritis (ReA) and
      osteoarthritis (OA) as well as correlations between GR activity and concentration
      of the major cartilage components in synovial fluid are presented in this study.
      We found significantly higher activity of GR in RA (about three-fold) and ReA
      (about two-fold) than in OA. In RA and ReA patients, GR activity in synovial
      fluid correlates negatively with the concentrations of collagen and degradation
      products of sulfated glycosaminoglycans. In OA patients the activity of GR was
      significantly lower than in RA and ReA, which positively correlated with the
      concentration of collagen and showed a tendency for positive correlation with the
      degradation products of sulfated glycosaminoglycans. Our results suggest that in
      RA and ReA patients increased activity of GR does not prevent the increased
      degradation of collagen and proteoglycans by ROS.

PMID- 19847335
TI  - Recent applications of intramolecular Diels-Alder reactions to natural product
      synthesis.
AB  - This tutorial review presents some recent examples of intramolecular Diels-Alder
      (IMDA) reactions as key complexity-generating steps in the total synthesis of
      structurally intricate natural products. The opportunities afforded by
      transannular (TADA) versions of the IMDA reaction in complex molecule assembly
      are also highlighted. The review is aimed at a wide audience, ranging from
      advanced undergraduates to seasoned practitioners of total synthesis; since this
      is an educational overview, only selected highlights from the period 2000-2009
      are presented, along with chosen references to other, more comprehensive,
      reviews.

PMID- 19847336
TI  - The art of total synthesis through cascade reactions.
AB  - The growing importance of cascade reactions reflects and imparts advances in the
      state of the art of organic synthesis and underscores the desire of synthetic
      chemists to achieve higher levels of elegance and efficiency. Besides their
      esthetic appeal, cascade processes offer economical and environmentally friendly
      means for generating molecular complexity. Because of their many advantages,
      these reactions have found numerous applications in the synthesis of complex
      molecules, both natural and designed. In this tutorial review, we highlight the
      design and execution of cascade reactions within the context of total synthesis
      as demonstrated with selected examples from these laboratories.

PMID- 19847337
TI  - The economies of synthesis.
AB  - In this tutorial review the economies of synthesis are analysed from both
      detailed and macroscopic perspectives, using case-studies from complex molecule
      synthesis. Atom, step, and redox economy are more than philosophical constructs,
      but rather guidelines, which enable the synthetic chemist to design and execute
      an efficient synthesis. Students entering the field of synthesis might find this
      tutorial helpful for understanding the subtle differences between these economic
      principles and also see real-world situations where such principles are put into
      practice.

PMID- 19847338
TI  - Bond formations by intermolecular and intramolecular trappings of acylketenes and
      their applications in natural product synthesis.
AB  - The reactive intermediates known as acylketenes exhibit a rich chemistry and have
      been extensively utilized for many types of inter- and intramolecular bond
      forming reactions within the field of organic synthesis. Characteristic reactions
      of acylketenes include cycloadditions, carbon-carbon bond-forming reactions, and
      nucleophilic capture with alcohols or amines to give beta-keto acid derivatives.
      In particular, the intramolecular capture of acylketene intermediates with
      pendant nucleophiles represents a powerful method for forming both medium-sized
      rings and macrocycles, often in high yield. This tutorial review examines the
      history, generation, and reactivity of acylketenes with a special focus on their
      applications in the synthesis of natural products.

PMID- 19847339
TI  - Biogenetically inspired syntheses of alkaloid natural products.
AB  - Since the synthesis of tropinone in the early 20th century, generations of
      chemists have looked to nature for inspiration in developing elegant syntheses of
      natural products. Analyzing molecules in their native context greatly enriches
      the chemist's understanding of nature's solution to the rapid generation of
      molecular complexity. In this tutorial review, we examine select examples from
      the alkaloid literature to highlight ways in which the close interplay of
      chemistry and biology have resulted in the development of elaborate biosynthetic
      hypotheses as well as strikingly beautiful syntheses. In addition, we present a
      case study on this topic through the lens of our total synthesis of (+)-11,11'
      dideoxyverticillin A.

PMID- 19847340
TI  - Heterocycles from cyclopropanes: applications in natural product synthesis.
AB  - The construction of heterocyclic compounds from activated cyclopropane
      derivatives offers an alternative strategy for the preparation of molecules that
      may be of interest from a structural or biological standpoint. Several newly
      developed methods provide access to densely functionalized heterocycles in a
      manner that can be considered useful for both diversity- and target-oriented
      synthetic approaches. This tutorial review focuses on the latter, describing
      recent developments and applications of cyclopropane ring-expansion reactions in
      natural product synthesis.

PMID- 19847341
TI  - Application of donor/acceptor-carbenoids to the synthesis of natural products.
AB  - The metal catalyzed reactions of diazo compounds have been broadly used in
      organic synthesis. The resulting metal-carbenoid intermediates are capable of
      undergoing a range of unconventional reactions, and due to their high energy,
      they are ideal for initiating cascade sequences leading to the rapid generation
      of structural complexity. This tutorial review will give an overview of the most
      versatile reactions of donor/acceptor carbenoids, an exciting class of
      intermediates capable of highly selective reactions. This will include
      cyclopropanation, [4 + 3] cycloaddition, and C-H functionalization methodologies.
      The application of this chemistry to the synthesis of a range of natural products
      will be described.

PMID- 19847342
TI  - Domino reactions of rhodium(II) carbenoids for alkaloid synthesis.
AB  - In this tutorial review, the rhodium(II)-catalyzed domino reactions of alpha
      diazo carbonyl compounds are summarized. The article will emphasize some of the
      more recent synthetic applications of the rhodium carbenoid
      cyclization/cycloaddition domino cascade for alkaloid synthesis. The many
      structurally diverse and highly successful examples of both oxa and azapolycyclic
      ring formation cited in this tutorial review clearly demonstrate that the domino
      cyclization/cycloaddition cascade of metallo carbenoids has evolved as an
      important strategy for the synthesis of nitrogen containing natural products.

PMID- 19847343
TI  - Aromatic compounds as synthons for 1,3-dicarbonyl derivatives.
AB  - This tutorial review covers the applications of aromatic compounds such as
      anisole derivatives as synthetic equivalents (synthons) for 1,3-dicarbonyl
      compounds. The aromatic nucleus is first converted under reductive Birch
      conditions to the corresponding 1,4-cyclohexadiene compound which is then
      subjected to ozonolysis. The reductive work-up of the ozonides generates the 1,3
      dicarbonyl compounds. The usefulness of this reaction sequence is demonstrated in
      several syntheses of complex molecules. A new access to 1,3-dicarbonyl compounds
      by an alternative approach utilising a cobalt-catalysed Diels-Alder reaction or a
      1,4-hydrovinylation reaction to generate the needed 1,4-diene derivatives is
      briefly discussed.

PMID- 19847344
TI  - Pericyclic domino reactions: concise approaches to natural carbocyclic
      frameworks.
AB  - This tutorial review highlights new research in the area of pericyclic domino
      reactions. It is directed towards chemists interested in cascading reactions and
      the total synthesis of natural products. Concise approaches to natural frameworks
      are described, as well as the application of domino reactions in the context of
      target-oriented synthesis and total synthesis.

PMID- 19847345
TI  - Enantioselective catalysis and complexity generation from allenoates.
AB  - Lewis base catalysis of reactions with allenoates using phosphine and amine
      nucleophiles has emerged as a key platform for the generation of molecular
      complexity. Investigations in this area have established a range of suitable
      coupling partners for allenoates, including electron-deficient olefins, imines,
      and aldehydes. This tutorial review will describe these methodologies, with a
      special emphasis on recent work regarding asymmetric reactions using chiral Lewis
      base catalysts.

PMID- 19847346
TI  - Applications of biotransformations and biocatalysis to complexity generation in
      organic synthesis.
AB  - This tutorial review provides a survey of syntheses in which an enzymatic step
      contributed to generating downstream molecular complexity in the target. The
      first part provides a guide to the types of enzymatic transformations suitable
      for incorporation into synthetic schemes. The principles of symmetry, especially
      the concept of "latent symmetry", which are often used to simplify
      enantiodivergent design of targets, are discussed next. The examples are
      discussed in the order of a degree of experimental difficulty associated with the
      execution of a particular biological technique. Lipase resolutions and
      desymmetrizations are discussed first followed by more advanced protocols
      involving oxidoreductase enzymes and ending with examples of syntheses that
      employ pathway engineering and directed evolution of proteins. Future prospects
      of biocatalytic methods as means of efficient preparation of target compounds are
      indicated. The authors hope that the review will serve to convince those
      synthetic chemists reluctant to use biological methods to include enzymatic
      procedures in their design.

PMID- 19847347
TI  - [3,3]-Sigmatropic rearrangements: recent applications in the total synthesis of
      natural products.
AB  - Among the fundamental chemical transformations in organic synthesis, the [3,3]
      sigmatropic rearrangement occupies a unique position as a powerful, reliable, and
      well-defined method for the stereoselective construction of carbon-carbon or
      carbon-heteroatom bonds. While many other reactions can unite two subunits and
      create a new bond, the strengths of sigmatropic rearrangements derive from their
      ability to enable structural reorganization with unmatched build-up of
      complexity. Recent applications that illustrate [3,3]-sigmatropic processes as a
      key concept in the synthesis of complex natural products are described in this
      tutorial review, covering literature from about 2001 through early 2009.

PMID- 19847348
TI  - Multi-component cycloaddition approaches in the catalytic asymmetric synthesis of
      alkaloid targets.
AB  - Cycloaddition reactions are attractive strategies for the rapid formation of
      molecular complexity in organic synthesis, as multiple bonds are formed in a
      single process. To this end, several research groups have been actively involved
      in the development of catalytic methods to activate readily accessible pi
      components to achieve cycloadditions. However, the use of C-N pi-components for
      the formation of heterocycles by these processes is less well developed. It has
      been previously demonstrated that the combination of different isocyanates with
      two alkynes yields pyridones of several types by metal-catalyzed [2 + 2 + 2]
      cycloadditions. The potential of this chemistry has been extended to alkenes as C
      C pi-components, allowing the formation of sp(3)-stereocenters. In this tutorial
      review directed towards [n + 2 + 2] cycloadditions of heterocumulenes, alkynes
      and alkenes, the recent advances in the catalytic asymmetric synthesis of
      indolizidine, quinolizidine and azocine skeletons are discussed.

PMID- 19847349
TI  - Synthetic approaches to the bicyclo[2.2.2]diazaoctane ring system common to the
      paraherquamides, stephacidins and related prenylated indole alkaloids.
AB  - The bicyclo[2.2.2]diazaoctane ring system is common to a number of highly
      biologically active secondary metabolites isolated from numerous species of
      fungi. In this tutorial review, we describe the varied synthetic approaches that
      have been employed to construct this ring system in the course of recent total
      synthesis endeavors, and this review should be of interest to synthetic organic
      chemists and natural product chemists. Detailed herein are a number of synthetic
      disconnections including intramolecular S(N)2' cyclizations, biomimetic Diels
      Alder reactions, radical cyclizations, and cationic cascade reactions.

PMID- 19847350
TI  - The development of endo-selective epoxide-opening cascades in water.
AB  - This tutorial review traces the development of endo-regioselective epoxide
      opening reactions in water. Templated, water-promoted epoxide-opening cyclization
      reactions can offer rapid access to subunits of the ladder polyethers, a
      fascinating and complex family of natural products. This review may be of
      interest to those curious about the ladder polyethers and their hypothesized
      biogenesis, about organic reactions in water, and about the development and
      application of cascade reactions in organic synthesis.

PMID- 19847352
TI  - Gold and platinum catalysis--a convenient tool for generating molecular
      complexity.
AB  - This critical review intends to familiarize the reader with the essence of pi
      acid catalysis, in particular with reactions or reaction cascades effected by
      gold and platinum complexes. Even though materialized in apparently different
      reactivity modes, such noble metal catalyzed processes can be easily rationalized
      on the basis of a uniform mechanistic scheme that is outlined in detail. The
      resulting increase in molecular complexity is illustrated by selected natural
      product total syntheses and the formation of various intricate non-natural
      compounds (106 references).

PMID- 19847351
TI  - Total synthesis of chiral biaryl natural products by asymmetric biaryl coupling.
AB  - This tutorial review highlights the use of catalytic asymmetric 2-naphthol
      couplings in total synthesis. The types of chirality, chiral biaryl natural
      products, prior approaches to chiral biaryl natural products, and other catalytic
      asymmetric biaryl couplings are outlined. The three main categories of chiral
      catalysts for 2-naphthol coupling (Cu, V, Fe) are described with discussion of
      their limitations and advantages. Applications of the copper catalyzed couplings
      in biomimetic syntheses are discussed including nigerone, hypocrellin, calphostin
      D, phleichrome, and cercosporin.

PMID- 19847353
TI  - Rapid formation of complexity in the total synthesis of natural products enabled
      by oxabicyclo[2.2.1]heptene building blocks.
AB  - This critical review showcases examples of rapid formation of complexity in total
      syntheses starting from 7-oxabicyclo[2.2.1]hept-5-ene derivatives. An overview of
      methods allowing synthetic access to these building blocks is provided and their
      application in recently developed synthetic transformations to structurally
      complex systems is illustrated. In addition, the facile access to a novel
      oxabicyclo[2.2.1]heptene derived building block is presented which significantly
      enlarges the possibilities of previously known chemical transformations and is
      highlighted in the enantioselective route to the core of the banyaside and
      suomilide natural products (107 references).

PMID- 19847354
TI  - Transition metal-catalyzed C-H activation reactions: diastereoselectivity and
      enantioselectivity.
AB  - This critical review discusses historical and contemporary research in the field
      of transition metal-catalyzed carbon-hydrogen (C-H) bond activation through the
      lens of stereoselectivity. Research concerning both diastereoselectivity and
      enantioselectivity in C-H activation processes is examined, and the application
      of concepts in this area for the development of novel carbon-carbon and carbon
      heteroatom bond-forming reactions is described. Throughout this review, an
      emphasis is placed on reactions that are (or may soon become) relevant in the
      realm of organic synthesis (221 references).

PMID- 19847357
TI  - [DNA damage in lymphocytes after irradiation with 211At and 188Re].
AB  - AIM: Ionising radiation produces many types of DNA lesions of different
      complexity. High linear energy transfer (LET) types of radiation are biological
      more effective than low LET radiation. In the present work we applied the single
      cell gel electrophoreses (comet assay) to study the induction of initial DNA
      damage, efficiency of repair and residual DNA damage in lymphocytes after
      treatment with 211At and 188Re. METHODS: Peripheral blood mononuclear cells
      (PBMC) were isolated from heparinized blood of healthy donors and irradiated with
      211At and 188Re at different doses. The comet assay was performed under alkaline
      and neutral conditions in order to detect the initial DNA damage and its repair.
      The measure of damage was % tail DNA (percentage of DNA in the tail). RESULTS:
      After treatment of cells with 188Re the initial DNA damage (% tail DNA) detected
      with the alkaline comet assay was higher than the damage measured for 211At. The
      neutral comet assay estimated higher tail intensities for 211At in contrast to
      188Re. Compared with the complete repair (10%) after irradiation with 188Re, the
      radiotoxicity of alpha particles indicated reduced rejoining of DNA strand breaks
      (60-80% residual damage). Rejoining of DNA damage measured by the neutral comet
      method detected about 70% unrepaired strand breaks for 211At and 188Re.
      CONCLUSIONS: There are major differences between the repair of strand breaks
      caused by 188Re and 211At detected by the alkaline comet assay. The DNA-damage
      induced by the high LET Emitter 211At remains nearly unrepaired detected by both
      alkaline and neutral comet assay. Represented data following irradiation of
      lymphocytes with alpha and beta particles demonstrated higher biological
      effectiveness of 211At by factors of 2.0-2.5.

PMID- 19847358
TI  - How to choose PET-CT or CT in the diagnosis and staging of lung cancer. Practical
      experience in China.
AB  - How to use CT and PET-CT rationally to raise diagnosis, staging and prognostic
      assessment of lung cancer to a higher level at the best cost-effect ratio is a
      subject that Chinese clinicians and radiologists should face conscientiously. We
      review the rational application of CT and PET-CT in four aspects of lung cancer,
      including screening and detection, morphologic evaluation, haemodynamic or
      metabolic feature evaluation, and follow-up, staging and prognostic evaluation.
      As PET-CT is only available in class III-A hospitals today, CT is the most
      popular equipment in China. PET-CT is more valuable only in cases where CT
      presentation of lung cancer is atypical or difficult to determine, or in cases
      where the diagnosis of lung cancer has been initially confirmed, for which
      clinical staging and decision concerning on therapeutic regimens are needed. We
      also recommend the current strategies of CT and PET-CT managing of SPN in China.

PMID- 19847359
TI  - [The brain mechanism of memory encoding and retrieval: a review on the fMRI
      studies].
AB  - Memory encoding and memory retrieval are two important processes of the memory.
      The main results of studies on the neural basis of the memory encoding and memory
      retrieval by functional magnetic resonance image (fMRI) technique were summarized
      in this review. The neural basis of memory encoding and retrieval phases varies
      with different materials, memory types, and age stages. It means that the neural
      networks of these memory activities are separate. The functional locations of the
      activated brain areas during memory encoding and during memory retrieval phases
      are overlapped with distinction. The activated brain areas of memory encoding
      mainly locate in the prefrontal lobe, the temporal lobe, the parietal lobe, the
      anterior hippocampus, the thalamus, and the basal ganglia (including the striatum
      and the marginal division of the striatum). The activated brain areas of memory
      retrieval mainly locate in the prefrontal lobe, the temporal lobe, the entorhinal
      cortex, the perirhinal cortex, the posterior hippocampus, the thalamus, and the
      basal ganglia. The anterior hippocampus is mainly activated during the encoding
      phase, whereas posterior hippocampus is mainly activated during the retrieval
      phase. The intensity of the activated cerebral cortex regions during the encoding
      phase is stronger than that during the retrieval phase, whereas the opposite
      activated pattern is found in the subcortical structures, mainly the basal
      ganglia and thalamus, during the two phases. It seems that the stimulation might
      activate certain cerebral cortex areas during the memory encoding phase, then the
      information is transported to the subcortical structures and comes back to the
      cerebral cortex to complete the memory retrieval phase. The encoding and
      retrieval phases of the memory are supposed to be accomplished by a neural
      circuit among the cerebral cortex, basal ganglia, thalamus and cerebral cortex,
      rather than the cerebral cortex only.

PMID- 19847360
TI  - Mediating roles of the vanilloid receptor TRPV1 in activation of rat primary
      afferent nociceptive neurons by formaldehyde.
AB  - The formalin test is a commonly used animal model of acute and tonic pain.
      However, the molecular targets of formaldehyde (FA, the main ingredient of the
      formalin solution) on primary nociceptor cells remain controversial. In this
      report, the effects of FA on electrophysiologically-identified primary nociceptor
      cells were evaluated in vitro and the roles of the vanilloid receptor TRPV1 in FA
      produced activation of primary nociceptors were also examined at both cellular
      and behavioral levels. Of 92 acutely dissociated dorsal root ganglion (DRG) cells
      recorded by current patch-clamp technique, 34% were discharged by FA application
      with the mean onset latencies of the first action potential (AP) being (367.34+/
      32.96) s. All the FA-sensitive cells were identified as nociceptor cells by their
      distinguishable features of AP including longer duration, existence of a hump (a
      shoulder or inflection) on the repolarizing phase, and longer after
      hyperpolarization of APs. Co-application of capsazepine (CPZ), a competitive
      antagonist of TRPV1 receptors, could block FA-evoked firing with partial
      inhibition on the membrane depolarization of all cells tested. Of another 160
      cells examined by confocal calcium imaging, 32% were shown to respond to FA with
      an intracellular Ca(2+) rise. Of 51 FA-sensitive cells, 67% were suppressed by
      CPZ, suggesting partial involvement of TRPV1 in mediation of the FA-evoked
      intracellular Ca(2+) rise. Under voltage-clamp mode, 41% of DRG cells were evoked
      to give rise to inward current with the remaining 59% being unchanged. In
      separate experiments on the other 56 FA-sensitive cells, concentration-dependent
      increase in the FA-evoked current amplitude was demonstrated. In comparison with
      controls, the FA-evoked inward current could be significantly suppressed by CPZ
      that was further enhanced by HC-030031, a TRPA1 selective antagonist. Finally,
      local effects of CPZ were confirmed in the formalin test and it was shown that
      the formalin-induced paw flinches were strongly suppressed by CPZ in phase 1 but
      with phase 2 being significantly suppressed only during 25-55 min. It is
      therefore concluded that FA can directly activate a subpopulation of primary
      nociceptor cells and the FA-induced AP discharges are likely to contribute mainly
      to phase 1, but not phase 2 of the formalin-induced nociception. The activation
      of primary nociceptor cells by FA is likely to be mediated, at least in part,
      through TRPV1 and/or TRPA1 receptors.

PMID- 19847361
TI  - Impaired neural coordination in hippocampus of diabetic rat.
AB  - In vitro electrical neurophysiological and behavioural studies have shown that
      diabetes mellitus negatively affects hippocampal function. In this study, by
      using in vivo extracellular recording, the spontaneous neural activity was
      obtained from hippocampus of anaesthetized rats in both streptozotocin-induced
      diabetes group and normal control group. Temporal relationship between neuronal
      firing and slow oscillation (1-4 Hz) of local field potentials (LFPs) in
      hippocampus was analyzed using coherence and phase locking measurement. Lower
      coherence value (0.617+/-0.028) was observed in diabetic rats than that in
      control rats (0.730+/-0.024) (P=0.005). Furthermore, phase-locking measurement
      using von Mises fitting parameterized by a concentration parameter kappa showed a
      lower degree (kappa= 0.347+/-0.113) of temporal coordination between neuronal
      spiking and slow oscillation of LFPs in the hippocampus of diabetic rats than
      that of normal ones (kappa= 1.174+/-0.134) (P<0.001). Both approaches
      demonstrated that diabetes can indeed impair the temporal coordination between
      neuronal spiking and slow oscillation of population activity in hippocampus. This
      observed neural coordination impairment may serve as a network level mechanism
      for diabetes-induced memory deterioration.

PMID- 19847362
TI  - [The expression of proto-oncogene c-erbB2 and its role in the initiation of
      primordial follicle growth in rat ovary].
AB  - Little is known about the factors that control the initiation of growth of
      primordial follicles. The objective of the present study was to investigate the
      effect of c-erbB2 on the onset of primordial follicle development, and whether c
      erbB2 mediates the effect of epidermal growth factor (EGF) in this process. We
      synthesized three pairs of siRNAs targeting the c-erbB2 mRNA and transferred them
      into the newborn rat ovary cultured in vitro with Metafectene. After siRNAs
      transfection, the efficiency of siRNAs was tested by examining c-erbB2 mRNA and
      protein levels. The level of c-erbB2 mRNA was reduced by 49.6%, 46.7% and 82.6%
      respectively after transfecting siRNA1, siRNA2 and siRNA3, and the level of ErbB2
      protein also reduced remarkably after siRNA3 transfection. c-erbB2 siRNA3
      significantly inhibited the primordial follicle initiation and development; EGF
      augmented primordial follicles formation, but the effect was abolished by c-erbB2
      siRNA3. All of these results suggest that c-erbB2 plays an important role in
      primordial follicle development and folliculogenesis initiation, and mediates the
      effect of EGF on primordial follicle development.

PMID- 19847363
TI  - Progesterone promotes propagation and viability of mouse embryonic stem cells.
AB  - It has been known that estrogen-17beta stimulates proliferation of mouse
      embryonic stem (mES) cells. To explore the function of another steroid hormone
      progesterone, we used MTT method and BrdU incorporation assay to obtain growth
      curves, clone forming assay to detect the propagation and viability of individual
      mES cells, Western blot to test the expression of ES cell marker gene Oct-4,
      fluorescence activated cell sorter (FACS) to test cell cycle, and real-time PCR
      to detect the expressions of cyclins, cyclin-dependent kinases and proto
      oncogenes. The results showed that progesterone promoted proliferation of mES
      cells. The number of clones was more in progesterone-treated group than that in
      the control group. The expression of pluripotency-associated transcriptional
      factor Oct-4 changed little after progesterone treatment as shown by Western
      blot, indicating that most of mES cells were in undifferentiated state. The
      results of FACS proved that progesterone promoted DNA synthesis in mES cells. The
      proportion of mES cells in S+G(2)/M phase was higher in progesterone-treated
      group than that in the control group. Cyclins and cyclin-dependent kinases, as
      well as proto-oncogenes (c-myc, c-fos) were up-regulated when cells were treated
      with progesterone. The results obtained indicate that progesterone promotes
      propagation and viability of mES cells. The up-regulation of cell cycle-related
      factors might contribute to the function of progesterone.

PMID- 19847364
TI  - [Role of MAPK and PKC signaling pathways in the regulation of c-erbB2 in the
      primordial follicles onset].
AB  - Our previous studies showed that the proto-oncogene c-erbB2 played an important
      role in primordial follicles growth. The present study was conducted to
      investigate the role of MAPK and PKC signaling pathways in the primordial
      follicle onset in neonatal rats, and the relationship between c-erbB2 and
      MAPK/PKC signaling pathways. Ovaries collected from 2-day-old Sprague-Dawley rats
      were cultured in the Waymouth culture system in vitro. Ovaries were transfected
      with c-erbB2 siRNA, or treated with PD98059 (50 mumol/L) or Calphostin (0.5
      mumol/L) in the culture medium. RT-PCR was performed to measure the expression of
      c-erbB2 mRNA, and Western blot analysis was performed to measure the expression
      of ErbB2, MAPK and PKC protein after the neonatal rat ovaries were cultured for 8
      d. The quantities of every-stage follicles of ovaries cultured for 8 d were
      obtained in histological section stained with hematoxylin eosin. The results
      showed that c-erbB2 siRNA reduced the levels of c-erbB2 mRNA (P<0.01) and the
      levels of ErbB2, MAPK and PKC protein (P<0.01) significantly. But the levels of c
      erbB2 mRNA and ErbB2 protein exhibited no change (P>0.05) in the ovaries cultured
      with PD98059 or Calphostin. After the ovaries were transfected with c-erbB2 siRNA
      or cultured with PD98059 or Calphostin for 8 d, the quantities of primary
      follicles and second follicles were lower than those in the control group (P<0.05
      or P<0.01), but the quantity of the primordial follicles was higher than that in
      the control group (P<0.01). These results suggest that proto-oncogene c-erbB2
      promotes the initiation of primordial follicle growth through the MAPK and PKC
      signal transduction, and c-erbB2 is possibly the upstream of PKC and MAPK
      signaling pathway in the regulation of primordial follicle onset.

PMID- 19847365
TI  - [Effects of parabolic flight on redox status in SH-SY5Y cells].
AB  - Space flight is known to produce a number of neurological disturbances. The
      etiology is unknown, but it may involve increased oxidative stress. A line of
      experimental evidence indicates that space flight may disrupt antioxidant defense
      system and result in increased oxidative stress. In vitro studies found that
      abundant of NO was produced in rat pheochromocytoma (PC12) cells, SHSY5Y
      neuroblastoma cells, and protein nitration was increased in PC12 cells within a
      simulated microgravity rotating wall bioreactor high aspect ratio vessel system
      or clinostat system. In the present study, we observed the change of redox status
      in SH-SY5Y cells after parabolic flight, and studied the effects of key redox
      molecule, thioredoxin (TRX), during the altered gravity. SH-SY5Y cells were
      divided into four groups: control cells, control cells transfected with TRX,
      flight cells and flight cells transfected with TRX. The expression levels of 3
      nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), TRX and thioredoxin
      reductase (TRXR) were observed by immunocytochemical method. It was shown that
      after parabolic flight, the staining of 3-NT and TRX were enhanced, while the
      expression level of TRXR was down-regulated compared with control. As for flight
      cells transfected with TRX, the staining of 3-NT and iNOS were weakened compared
      with flight cells. These results obtained suggest that altered gravity may
      increase protein nitration, down-regulate TRXR and elicit oxidative stress in SH
      SY5Y cells, while TRX transfection could partly protect cells against oxidative
      stress induced by parabolic flight.

PMID- 19847366
TI  - [The neuroregulatory effect of cerebellar fastigial nucleus stimulation on
      gastric ischemia-reperfusion injury in rats].
AB  - In the present study, rat model of gastric ischemia-reperfusion (GI-R) injury was
      established by clamping the celiac artery for 30 min followed by 1 h of
      reperfusion. Subsequently, the regulatory effect of electrical stimulation of
      cerebellar fastigial nucleus (FN) on GI-R injury and its neural mechanisms were
      investigated in Sprague-Dawley rats. The results are as follows. Electrical
      stimulation of the cerebellar FN not only obviously attenuated the GI-R injury in
      an intensity-dependent manner, but also decreased the apoptosis rate of gastric
      mucosal cells. Chemical lesion of FN eliminated the protective effect of
      electrical stimulation of FN on GI-R injury. Electrical stimulation of cerebellar
      FN decreased both the frequency and amplitude of the discharges of greater
      splanchnic nerve, but it could not change the discharge of greater splanchnic
      nerve following the lesion of the lateral hypothalamic area (LHA). After
      bilateral section of the greater splanchnic nerves, electrical stimulation of the
      FN also attenuated the GI-R injury. Chemical lesion of the LHA reversed the
      protective effect of electrical stimulation of FN on GI-R injury. Electrical
      stimulation of FN increased the activity of superoxide dismutase (SOD), but
      decreased the content of malondialdehyde (MDA) in gastric mucosa under GI-R.
      These results indicate that the cerebellar FN may regulate GI-R injury.
      Therefore, the cerebellar FN is an important brain site protecting the stomach
      against GI-R. The LHA and greater splanchnic nerves participate in the regulatory
      effects of cerebellar FN stimulation on GI-R injury. In addition, antioxidation
      may also be involved in the protection mechanism of cerebellar FN stimulation.

PMID- 19847367
TI  - [Developmental regulation of long term potentiation at layer II/III to II/III
      synapses of rat visual cortex].
AB  - In the present research, patch-clamp whole-cell recording was used to study the
      developmental changes of the internal horizontal synaptic plasticity in layer
      II/III of rats' primary visual cortices. Pairing stimulation was used to induce
      long term potentiation (LTP) of neurons in layer II/III from layer II/III and
      layer IV. The data indicate that: (1) Responses of layer II/III neurons can be
      evoked independently at II/III-II/III and IV-II/III synapses by horizontal and
      vertical stimulations; (2) LTP can be induced from neurons in the layer II/III by
      horizontal tetanic stimulation at II/III-II/III synapses till postnatal day12
      (P12, before eyes open); (3) Meanwhile, only short term potentiation (STP) at IV
      II/III synapses can be induced by horizontal tetanic stimulation before eyes
      open; (4) After P12, a robust LTP at IV-II/III synapses can be induced by
      horizontal tetanic stimulation; (5) At P14, when vertical and horizontal tetanic
      stimulations were given to the same neuron, the LTP at IV-II/III synapses was
      weaker than that induced by vertical stimulation alone, suggesting that vertical
      synaptic modification was negatively regulated by horizontal inputs when two
      direction synaptic inputs were presented at the same time; (6) Spontaneous
      responses of AMPA receptors (AMPARs) in the layer II/III neuron of rats' primary
      visual cortices are regulated by the development. The frequency of AMPARs
      mediated postsynaptic currents was at a low level before eyes open, increased
      sharply at P12-P14, and slightly decreased after P18. And the amplitude of
      spontaneous AMPARs currents slowly decreased after P12. The results demonstrated
      that both the strength of horizontal synaptic modification and the effects of
      horizontal inputs on the vertical synaptic connection are regulated by the
      development. II/III-II/III synaptic communication has dual effects on the IV
      II/III synapses, which may be involved in a competitive machinery of neural
      circuitry maturation and the formation of visual function columns.

PMID- 19847368
TI  - [Selectivity for the rate of frequency-modulated sweeps and its affecting factors
      in the inferior collicular neurons of mouse].
AB  - Both animal communication sounds and human speech contain frequency-modulated
      (FM) sweeps. Although the selectivity for the rate of FM sweeps in neurons has
      been found in many kinds of animals at different levels of the central auditory
      structures, the underlying neural mechanism is still not clear. Using
      extracellular single unit recording techniques, we examined the selectivity for
      the rate of FM sweeps in the inferior colliculus (IC) neurons of the Kunming
      mouse (Mus musculus, Km) in the free-field stimulation conditions and determined
      its affecting factors. Totally, 102 neurons were recorded successfully, among
      which 42 neurons (41.2%) displayed a duration tuning pattern under pure tone (PT)
      stimulus. The percentages of short-pass, band-pass, and long-pass neurons were
      22.6% (23/10), 8.8% (9/102), 9.8% (10/102), respectively. The other 60 neurons
      (58.8%) did not show any duration tuning features. Under FM stimulus, the
      majority of duration tuning neurons (78.6%, 33/42) showed the selectivity for the
      rate of FM sweeps. For these neurons, the type of rate selectivity was determined
      by the duration tuning features, but it was not related to the modulation range
      (MR) of FM. In a small fraction of duration tuning neurons (21.4%, 9/42), the
      rate selectivity was correlated with the MR, but uncorrelated with the duration
      tuning features. On the other hand, more than half of the non-duration tuning
      neurons (53.3%, 32/60) exhibited the rate selectivity under FM stimulus, and
      almost all of them (31/32) showed fast-rate selectivity. Nevertheless, there were
      8 neurons (in 32) displaying the same best rate at different MR, indicating that
      they were real rate-selective neurons. Our results indicate that the selectivity
      for the rate of FM sweeps is co-determined by duration tuning features and sweep
      bandwidth. Only a few of inferior colliculus neurons belong to real rate
      selectivity neurons in the mouse.

PMID- 19847369
TI  - [Effect of apelin on hypoxic pulmonary hypertension in rats: role of the NO
      pathway].
AB  - To investigate the effectiveness and mechanism of apelin against pulmonary
      hypertension and pulmonary vascular remodeling induced by hypoxia in rats, 24
      male Sprague-Dawley rats were randomly divided into normal control (NC) group, 4
      week hypoxia (HH) group and 4-week hypoxia with apelin (HA) group (each n=8). The
      rats of hypoxic group were placed in an isobaric hypoxic chamber, in which O2 and
      CO2 content was maintained at 9%-11% and <3%, respectively, for 4 weeks (8 h/d, 6
      d/week). [pGlu]apelin-13 (10 nmol/kg per day, 28 d) was administered
      subcutaneously by osmotic mini-pump before hypoxia treatment in HA group. L
      arginine (L-Arg) uptake of pulmonary artery was assay by [3H]-L-Arg, while nitric
      oxide synthase (NOS) activity of pulmonary tissue, and nitrate/nitrite (NO2(
      )/NO3(-)) concentrations in pulmonary tissue and plasma were detected by
      colorimetric technique and nitrate reductase method, respectively. The results
      showed that mean pulmonary arterial pressure, the ratio value of right ventricle
      weight to left ventricle plus septum weight, the relative medial thickness, and
      the relative medial area of pulmonary arterioles were higher in HH group than
      those in NC group (all P<0.01), while these indices were lower in HA group than
      those in HH group (P<0.05 or P<0.01). Compared with those in HH group, the uptake
      of 0.5, 5 and 10 nmol/L [3H]-L-Arg in pulmonary artery in HA group increased by
      121.4% (P<0.01), 85.0% (P<0.05) and 61.5% (P<0.05), respectively; cNOS activity
      of pulmonary tissue increased by 74.3%, while iNOS activity decreased by 25.0%
      (all P<0.01); and NO2(-)/NO3(-) concentrations in pulmonary tissue and plasma
      increased by 97.6% and 48.0% (all P<0.05), respectively. Taken together, our
      results suggest that apelin has a prophylactic effect against hypoxic pulmonary
      hypertension in rats, and that the mechanism of this effect is possibly
      associated with activation of the L-Arg/NOS /NO pathway.

PMID- 19847370
TI  - [Ca(2+)-dependent potassium channels play important roles in regulatory volume
      decrease in human nasopharyngeal carcinoma cells].
AB  - It has been shown that cell volume regulation mechanisms play important roles in
      various cell functions. We demonstrated previously that volume-activated chloride
      channels were involved in cell volume regulation. The present study aimed to
      clarify the roles of various types of potassium channels in regulatory volume
      decrease (RVD) induced by hypotonic challenges in human nasopharyngeal carcinoma
      cells (CNE-2Z cells). The whole-cell patch clamp technique was used to record
      hypotonic challenge-induced potassium currents. During current recordings, cells
      were held at 0 mV and stepped to +/-46 and +/-92 mV, repeatedly. The cell volume
      was computed from cell diameters. The changes of cell volume were monitored and
      analyzed by the time-lapse imaging technique. The results showed that the
      exposure to 160 mOsm/L hypotonic solution caused the cells to swell by (144.5+/
      4.2)%, activated a potassium current (59.2 pA/pF+/-13.3 pA/pF at 92 mV), and
      induced RVD. Cell volume was recovered from hypotonic challenge-induced swelling
      by (48.9+/-4.6)% after 20 min. The potassium current (at 92 mV) and RVD were
      inhibited by the calcium-dependent potassium channel blocker, clotrimazole (100
      mumol/L), by (98.5+/-2.8)% and (89.3+/-4.9)%, respectively. Depletion of
      extracellular calcium prevented the activation of the hypotonic challenge-induced
      potassium current and inhibited the process of RVD. The voltage-gated potassium
      channel blocker, 4-AP (5 mmol/L), partially inhibited the hypotonic challenge
      activated potassium currents by (66.6+/-5.3)% (at 92 mV). These results suggest
      that the Ca(2+)-dependent potassium channel is the main component of volume
      activated potassium channels and plays an important role in volume regulation of
      CNE-2Z cells. The voltage-gated potassium channels may also contribute in part to
      the formation of the volume-activated potassium current.

PMID- 19847371
TI  - [Biological characteristics of hematopoietic progenitor cells at different stages
      of hematopoietic development].
AB  - The aim of the present paper is to better understand the mechanism of
      hematopoietic development through studying the biological characteristics of
      hematopoietic progenitor cells at different stages of development. Firstly, the c
      kit expression levels of the mononuclear cells from murine embryonic aorta-gonad
      mesonephros (AGM) region at embryonic day (E)10.5 and E11.5, fetal liver (FL) at
      E12.5, E14.5, E16.5, E18 and bone marrow (BM) were assayed with fluorescence
      activated cell sorting (FACS). Secondly, hematopoietic progenitor cells derived
      from AGM at E10.5, FL at E14.5 and BM were isolated by using c-kit microbeads.
      Isolated c-kit(+) population cells from AGM, FL and BM were then co-cultured with
      E14.5 FL-derived stromal cells in transwell co-culture system in vitro. After 3,
      7, 10 days of co-culture, numerous floating cells were generated. The floating
      cells generated in transwell inserts were collected for FACS cell count,
      migration activity detection and colony forming unit (CFU) formation assay. The
      results showed that the c-kit was highly expressed in E10.5 AGM, with the
      percentage of c-kit(+) cells declining during AGM development. c-kit expression
      was highly expressed again in E12.5 FL, declining along with the progressive
      development of the FL region. Co-cultured with FL-derived stromal cells, E10.5
      AGM-derived c-kit(+) cells produced the highest number of hematopoietic cells,
      while BM-derived c-kit(+) cells produced the lowest number of hematopoietic
      cells. Compared with E10.5 AGM-derived c-kit(+) cells, E14.5 FL- and BM- derived
      c-kit(+) cells inclined to differentiate after 7 to 10 days of culture in vitro.
      E10.5 AGM and E14.5 FL-derived c-kit(+) cells exhibited a higher migration
      activity than BM-derived c-kit(+) cells. Moreover, E10.5 AGM-derived c-kit(+)
      cells showed a higher ability to form mixed colony-forming unit (CFU-Mix) colony.
      In conclusion, compared with FL- and BM-derived c-kit(+) cells, E10.5 AGM-derived
      c-kit(+) hematopoietic progenitor cells exhibit better proliferation, migration
      potential, and have a higher ability to maintain the undifferentiation state in
      vitro, providing an insight into their clinical manipulation.

PMID- 19847372
TI  - [Ameliorative effects of exogenous sulfur dioxide on lipopolysaccharide-induced
      acute lung injury in rats].
AB  - To investigate the influence of sulfur dioxide (SO2) on lipopolysaccharide (LPS)
      induced acute lung injury (ALI), we examined the influence of exogenous SO2 on
      pulmonary tissue inflammatory response. A rat model of ALI induced by intravenous
      (IV) injection of LPS was developed. Male Sprague-Dawley (SD) rats were divided
      into four groups randomly: control group, LPS group, LPS plus SO2 group (IV
      injection of 0.5 mL Na2SO3/NaHSO3 10 min before LPS administration) and SO2 group
      (only given Na2SO3/NaHSO3). Animals were sacrificed 6 h after agent
      administration. Lung weight/body weight ratio (LW/BW) was measured and
      calculated. Morphological changes of lung tissues were observed. The number of
      polymorphonuclear neutrophil (PMN) in the bronchoalveolar lavage fluid (BALF),
      intercellular adhesion factor-1 (ICAM-1) expression in the lung tissue and IL-1,
      IL-6 and IL-10 levels in the serum were tested. The results showed that, compared
      to control rats, the LPS-treated rats had severe injuries of lung tissues and an
      increased LW/BW, increased index of quantitative assessment (IQA) score,
      increased PMN number in the BALF, increased ICAM-1 expression in the lung tissue
      and increased IL-1, IL-6 and IL-10 levels in the serum 6 h after LPS injection.
      Administration of the SO2 donor, Na2SO/3NaHSO3, into LPS-treated rats reduced the
      LW/BW, PMN number and ICAM-1 expression, and alleviated the degree of ALI
      (measured by the IQA score). In addition, Na2SO3/NaHSO3 decreased IL-1 and IL-6
      levels, but increased IL-10 level in the serum. There were no significant
      differences in the above indexes between SO2-treated rats and control rats. These
      results suggest that exogenous SO2 could inhibit the pulmonary tissue
      inflammatory response in rats with LPS-induced ALI.

PMID- 19847373
TI  - Racism, mental illness and social support in the UK.
AB  - PURPOSE: The difference in risk of mental illness in UK ethnic minorities may be
      related to a balance between specific risk factors such as racial discrimination
      and mediating factors such as social support. We investigated whether social
      support from friends or relatives reduces the cross-sectional association between
      perceived racism and the risk of mental illness in an ethnic minority group.
      METHODS: We conducted secondary analyses of nationally representative community
      samples of five UK ethnic minority groups (EMPIRIC dataset; n = 4,281) using
      multiple regression techniques. RESULTS: We found that the associations between
      perceived racism, common mental disorder and potentially psychotic symptoms were
      mainly independent of social support as measured by the number of close persons
      and their proximity to the individual. CONCLUSION: Social support when measured
      in this way does not mediate the associations between perceived racism and mental
      ill health in this population-based sample.

PMID- 19847374
TI  - Effect of household processing on fenazaquin residues in okra fruits.
AB  - Fenazaquin (4-[[4 (1,1-dimethylethyl) phenyl] ethoxy]quinazoline) is a new
      acaricide of the quinazoline class. Residue levels of fenazaquin were determined
      in unprocessed and processed okra fruits to evaluate the effect of different
      processes (washing, boiling and washing followed by boiling) in reduction of
      residues of this pesticide in okra. The study was carried out on okra crop
      (Variety, Varsha Uphar) in research farm of Chaudhary Charan Singh Haryana
      Agricultural University, Hisar with application of fenazaquin (Magister 10 EC) @
      125 ga.i./ha (Single Dose, T(1)) and 250 g a.i./ha (Double Dose, T(2)). Samples
      of okra fruits were collected on 0, 3, 7, 15 days after treatment and at harvest
      (30 days). Residues were estimated by gas chromatograph equipped with capillary
      column and nitrogen phosphorus detector. Residues reached below maximum residue
      limit of 0.01 mg/kg at harvest. The residues dissipated with half-life period of
      3.13 days at lower dose and 4.43 days at higher dose. Processing is shown to be
      very effective in reducing the levels of fenazaquin residues in okra fruits.
      Maximum reduction (60-61%) was observed by washing + boiling followed by
      boiling/cooking (38-40%) and then by washing (31-32%).

PMID- 19847375
TI  - Does prolonged warfarin exposure potentiate coronary calcification in humans?
      Results of the warfarin and coronary calcification study.
AB  - Warfarin has been shown to accelerate vascular calcification in experimental
      animals, and possibly humans, through inhibition of the vitamin K-dependent
      protein matrix gla protein, a potent inhibitor of tissue calcification. We
      performed a cross-sectional analysis of the extent of coronary artery
      calcification (CAC) in patients without coronary heart disease, currently taking
      or referred for warfarin therapy. The primary end point was severity of CAC
      measured by electron beam computed tomography attributed to duration of warfarin
      use, after adjustment for cardiovascular risk factors. Seventy patients (46 men,
      mean age 68 +/- 13 years) were enrolled from three groups of warfarin use
      duration: (1) <6 months (n = 31, mean duration 1 +/- 1 months), (2) 6-24 months
      (n = 11), and (3) >24 months (n = 28, mean 67 +/- 40 months). Overall, the mean
      total CAC score (Agatston) was 293 +/- 560: group 1 (175 +/- 285), group 2 (289
      +/- 382), and group 3 (426 +/- 789). In univariate analysis, there was a
      nonsignificant trend to increased CAC with increasing warfarin exposure (P =
      0.18). Bivariate analysis revealed no correlation between warfarin duration and
      CAC score (r = 0.075, P = 0.537). Linear regression for the independent variable
      coronary calcium score controlling for warfarin treatment duration and intensity
      (duration of warfarin use months x mean INR), Framingham risk score, and
      creatinine clearance showed that only the Framingham risk score was associated
      with CAC (P = 0.001). Among patients without known coronary heart disease,
      duration of warfarin exposure was not associated with extent of coronary
      calcification.

PMID- 19847377
TI  - A passion for research.
AB  - During my postdoctoral training in Severo Ochoa's laboratory, I determined the
      direction of reading of the genetic message and I discovered two proteins in
      Escherichia coli involved in the initiation of protein synthesis. After my return
      to Spain, I have been working with the Bacillus subtilis phage varphi29. We
      discovered a protein covalently linked to the 5' DNA ends that is the primer for
      the initiation of varphi29 DNA replication. We also found that the phage-encoded
      DNA polymerase has unique properties such as processivity and strand displacement
      activity. These properties, in addition to its high fidelity, have made the
      varphi29 DNA polymerase the ideal enzyme for DNA amplification, both for rolling
      circle and whole-genome amplification. I am happy to say that the work carried
      out in my laboratory has been possible thanks to many brilliant students and
      collaborators, most of whom have become high quality independent scientists.

PMID- 19847376
TI  - The biceps brachii muscle and its distal insertion: observations of surgical and
      evolutionary relevance.
AB  - BACKGROUND: A sound understanding of the anatomy of the biceps brachii and
      possible anatomical variants is necessary to manage distal biceps injury. The
      present study was performed to define the anatomy of the biceps brachii with
      particular focus on the conformation of the distal biceps tendon, and its
      relationship of the two heads of the biceps brachii. METHODS: Twenty cadaver
      specimens were dissected and both qualitative and quantitative observations were
      made of a series of features relating to the biceps muscle and its tendon.
      RESULTS AND CONCLUSION: The investigation revealed anatomical variations
      including supernumerary heads (20%) and 'fusion' of the muscle proximal to tendon
      formation and a spiralling arrangement of the tendon in its approach to the
      radial tuberosity. The data from the present study was reviewed in the context of
      previous studies on the anatomy of this muscle and speculation on the
      evolutionary basis of the variations and their clinical implications are
      discussed.

PMID- 19847378
TI  - Migration of reticulated hyaluronic acid implant [SK-GEL] following deep
      sclerectomy.
AB  - A new complication after deep sclerectomy with implant is presented as a case
      report. A 42-year-old male with uncontrolled primary open-angle glaucoma
      underwent nonpenetrating deep sclerectomy (NPDS) with an SK-GEL implant in his
      left eye. Two months after surgery the implant was noted to migrate into the
      subconjunctival space. Seven months later the implant was stable in the new
      position without complication. Implant migration into the subconjunctival space
      is a possible complication of NPDS.

PMID- 19847379
TI  - [Obituary for Professor Dr. med Wolfgang Stoll : 23.09.1947-08.08.2009].

PMID- 19847380
TI  - [An unusual case of carotid arrosion bleeding].
AB  - Carotid bleeding is one of the most severe complications in ear, nose and throat
      (ENT) surgery. It is a rare complication in patients with cancer of the head and
      neck after radiochemotherapy. We report the case of a 65-year-old man who
      suffered from cancer of the tonsils (pT2pN1M0) and was treated in 1987 with
      surgery and local chemotherapy. Since then he reported recurrent bleeding in the
      left cervical region especially during physical exertion. The patient was re
      operated and during surgery the tip of a catheter was found in the external
      carotid artery, obviously a remnant from a catheter for intra-arterial
      chemotherapy. The tip was removed, the defect closed and covered with a
      pectoralis major muscle flap.

PMID- 19847381
TI  - [Surgical treatment of the multiple trauma patient. Responsibility from site of
      the accident up to rehabilitation].

PMID- 19847382
TI  - Gene cloning, expression, and characterization of a family 51 alpha-L
      arabinofuranosidase from Streptomyces sp. S9.
AB  - An alpha-L-arabinofuranosidase gene, abf51S9, was cloned from Streptomyces sp. S9
      and successfully expressed in Escherichia coli BL21 (DE3). The full-length gene
      consisted of 1,506 bp and encoded 501 amino acids with a calculated mass of 55.2
      kDa. The deduced amino acid sequence was highly homologous with the alpha-L
      arabinofuranosidases belonging to family 51 of the glycoside hydrolases. The
      recombinant protein was purified to electrophoretic homogeneity by Ni-NTA
      affinity chromatography and subsequently characterized. The optimal pH and
      temperature for the recombinant enzyme were 6.0 and 60 approximately 65 degrees
      C, respectively. The enzyme showed a broad pH range of stability, retaining over
      75% of the maximum activity at pH 5.0 to 11.0. The specific activity, K (m), and
      V (max) with p-nitrophenyl-alpha-L-arabinofuranoside as substrate were 60.0 U mg(
      1), 1.45 mM, and 221 mumol min(-1) mg(-1), respectively. Abf51S9 showed a mild
      but significant synergistic effect in combination with xylanase on the
      degradation of oat-spelt xylan and soluble wheat arabinoxylan substrates with a
      1.19- and 1.21-fold increase in the amount of reducing sugar released,
      respectively. These favorable properties make Abf51S9 a good candidate in various
      industrial applications.

PMID- 19847383
TI  - Identification of Saccharomyces cerevisiae genes involved in the resistance to
      phenolic fermentation inhibitors.
AB  - Saccharomyces cerevisiae was exposed to inhibitory concentrations of the three
      phenolic phenylpropanoids: coniferyl aldehyde, ferulic acid, and isoeugenol.
      Deoxyribonucleic acid microarray analysis was employed as one approach to
      generate a set of candidate genes for deletion mutant analysis to determine the
      potential contribution of the corresponding gene products to the resistance
      against toxic concentrations of phenolic fermentation inhibitors. Three S.
      cerevisiae deletion mutants with increased sensitivity to coniferyl aldehyde were
      identified: yap1Delta, atr1Delta, and flr1Delta. The rate of reduction of
      coniferyl aldehyde to coniferyl alcohol decreased sixfold when the gene encoding
      the transcriptional activator Yap1p was deleted, and threefold when the Yap1p
      controlled genes encoding Atr1p and Flr1p were deleted. Growth, glucose
      consumption, and ethanol formation progressed after a lag phase during which
      coniferyl aldehyde reduction and coniferyl alcohol formation occurred. The
      results link ATR1, FLR1, and YAP1 by their ability to confer resistance to
      coniferyl aldehyde and show that deletion of any of these three genes impairs the
      ability of S. cerevisiae to withstand coniferyl aldehyde and detoxify it by
      reduction. Furthermore, the results suggest that overexpression of ATR1, FLR1,
      and YAP1 is of interest for the construction of novel yeast strains with improved
      resistance against inhibitors in lignocellulose hydrolysates.

PMID- 19847384
TI  - [Ultrasound diagnostics of renal blood vessels and transplant kidney].
AB  - Ultrasound is usually the first imaging technique used in clinical practice for
      the visualization of renal blood vessels, especially when there is suspicion of
      renal artery stenosis. Apart from B-mode ultrasound, colour Doppler ultrasound,
      pulsed-wave Doppler are used as well as contrast-enhanced ultrasound, which is
      being used more and more as a routine technique. Ultrasound is important in
      nephrology for the detection of renal artery stenosis and the resistance indices
      from pulse-wave Doppler are also helpful in acute renal failure. Nevertheless
      resistance indices should be used carefully and always by being aware of the
      pitfalls of this parameter.Another field of application for ultrasound is imaging
      of renal blood vessel damage as a result of trauma or iatrogenic damage caused
      during a biopsy. In this setting contrast-enhanced ultrasound appears to be a
      suitable and highly sensitive tool for the detection of active bleeding and for
      visualizing the extent and dynamics of expansion of a hematoma.Ultrasonography is
      frequently used in the field of kidney transplants for the diagnostics of
      drainage obstructions, perfusion disturbances, transplant arterial stenoses and
      lymphoceles. Furthermore, ultrasound is exceptionally well suited for follow-up
      observation after diagnostic or therapeutic measures (e.g. biopsy and placement
      or removal of DJ catheters).

PMID- 19847385
TI  - [Palliative systemic therapy of castration-resistant prostate cancer: current
      developments].
AB  - Androgen withdrawal or surgical castration remains the standard therapy for
      advanced prostate cancer disease. Even for castration-resistant prostate cancer
      the therapeutic option of docetaxel-based chemotherapy is well studied and
      defined. Facing disease progression after docetaxel-based therapy there are
      multiple options to continue therapy but the evidence level is rather poor. In
      the last few years targeted therapy and immunomodulation have been the focus of
      clinical trials. The presented manuscript intends to provide an overview of
      classical cytostatic agents, endothelin inhibitors, immunotherapy, modified
      hormone therapy, multikinase inhibitors and radionuclide approaches which are
      currently under investigation for implementation in the clinical setting.

PMID- 19847386
TI  - Identification and mapping of molecular markers linked to the tuberculate fruit
      gene in the cucumber (Cucumis sativus L.).
AB  - Warty fruit is one of the highly valuable external quality traits related to the
      market values of cucumber. Genetic analysis has shown that a single dominant
      gene, Tu (Tuberculate fruit), determines the warty fruit trait in the cucumber
      plant. An F(2) population (247 individuals) from the cross of S06 x S52 was used
      for the mapping of the Tu/tu locus. By combining bulked segregant analysis with
      the sequence-related amplified polymorphism (SRAP) and simple sequence repeat
      (SSR) markers, 15 markers (9 SRAPs and 6 SSRs) linked to the Tu/tu locus were
      identified. Of nine SRAP markers, three closely linked to the Tu/tu locus were
      successfully converted into sequence characterized amplified region (SCAR)
      markers. The Tu/tu locus was mapped between the co-dominant SSR marker SSR16203
      and the SCAR marker C_SC933, at a genetic distance of 1.4 and 5.9 cM,
      respectively. Then the linked SSR markers in the study were used as anchor loci
      to locate the Tu/tu locus on cucumber chromosome 5. Moreover, the validity
      analysis of the C_SC69 and C_SC24 markers was performed with 62 cucumber lines of
      diverse origins, showing that the two SCAR markers can be used for marker
      assisted selection (MAS) of the warty fruit trait in cucumber breeding. The
      information provided in this study will facilitate the map-based cloning of the
      Tu/tu gene.

PMID- 19847387
TI  - QTLs for the elongation of axile and lateral roots of maize in response to low
      water potential.
AB  - Changes in root architecture and the maintenance of root growth in drying soil
      are key traits for the adaptation of maize (Zea mays L.) to drought environments.
      The goal of this study was to map quantitative trait loci (QTLs) for root growth
      and its response to dehydration in a population of 208 recombinant inbred lines
      from the International Maize and Wheat Improvement Center (CIMMYT). The parents,
      Ac7643 and Ac7729/TZSRW, are known to be drought-tolerant and drought-sensitive,
      respectively. Roots were grown in pouches under well-watered conditions or at low
      water potential induced by the osmolyte polyethylene glycol (PEG 8000). Axile
      root length (L (Ax)) increased linearly, while lateral root length (L (Lat))
      increased exponentially over time. Thirteen QTLs were identified for six seedling
      traits: elongation rates of axile roots (ER(Ax)), the rate constant of lateral
      root elongation (k (Lat)), the final respective lengths (L (Ax) and L (Lat)), and
      the ratios k (Lat)/ER(Ax) and L (Lat)/L (Ax.) While QTLs for lateral root traits
      were constitutively expressed, most QTLs for axile root traits responded to water
      stress. For axile roots, common QTLs existed for ER(Ax) and L (Ax). Quantitative
      trait loci for the elongation rates of axile roots responded more clearly to
      water stress compared to root length. Two major QTLs were detected: a QTL for
      general vigor in bin 2.02, affecting most of the traits, and a QTL for the
      constitutive increase in k (Lat) and k (Lat)/ER(Ax) in bins 6.04-6.05. The latter
      co-located with a major QTL for the anthesis-silking interval (ASI) reported in
      published field experiments, suggesting an involvement of root morphology in
      drought tolerance. Rapid seedling tests are feasible for elucidating the genetic
      response of root growth to low water potential. Some loci may even have
      pleiotropic effects on yield-related traits under drought stress.

PMID- 19847388
TI  - Rdr3, a novel locus conferring black spot disease resistance in tetraploid rose:
      genetic analysis, LRR profiling, and SCAR marker development.
AB  - Black spot disease of rose, incited by the fungus Diplocarpon rosae, is found
      worldwide and is the most important disease of garden roses. A gene-for-gene
      interaction in this pathosystem is evidenced by the presence of pathogenic races
      of D. rosae and the previous discovery of a dominant resistance allele at the
      Rdr1 locus in the diploid Rosa multiflora. The objective of the present study was
      to genetically analyze resistances to North American black spot races 3, 8, and 9
      previously reported in tetraploid roses. Resistance to North American races 3 and
      8 segregated 1:1 in multiple F(1) populations, indicating that both are conferred
      by dominant alleles at single loci and are present in simplex (Rrrr)
      configuration. Gene pyramiding was demonstrated by combining both resistances
      into single genotypes. Resistance to race 9 was partial and segregated in a
      quantitative fashion. Analysis of these populations with microsatellite markers
      previously developed for Rdr1 revealed that the gene conferring race 3 resistance
      resides within the same R gene cluster as Rdr1. Race 8 resistance segregated
      independently and is, therefore, a novel locus for black spot resistance in rose
      which we have named Rdr3. NBS and LRR profiling were used in a bulked segregant
      analysis to identify a marker 9.1 cM from Rdr3, which was converted to a SCAR
      marker form for marker-assisted breeding.

PMID- 19847389
TI  - A universal core genetic map for rice.
AB  - To facilitate the creation of easily comparable, low-resolution genetic maps with
      evenly distributed markers in rice (Oryza sativa L.), we conceived of and
      developed a Universal Core Genetic Map (UCGM). With this aim, we derived a set of
      165 anchors, representing clusters of three microsatellite or simple sequence
      repeat (SSR) markers arranged into non-recombining groups. Each anchor consists
      of at least three, closely linked SSRs, located within a distance below the
      genetic resolution provided by common, segregating populations (<500
      individuals). We chose anchors that were evenly distributed across the rice
      chromosomes, with spacing between 2 and 3.5 Mbp (except in the telomeric regions,
      where spacing was 1.5 Mbp). Anchor selection was performed using in silico tools
      and data: the O. sativa cv. Nipponbare rice genome sequence, the CHARM tool,
      information from the Gramene database and the OrygenesDB database. Sixteen AA
      genome accessions of the Oryza genus were used to evaluate polymorphisms for the
      selected markers, including accessions from O. sativa, O. glaberrima, O. barthii,
      O. rufipogon, O. glumaepatula and O. meridionalis. High levels of polymorphism
      were found for the tested O. sativa x O. glaberrima or O. sativa x wild rice
      combinations. We developed Paddy Map, a simple database that is helpful in
      selecting optimal sets of polymorphic SSRs for any cross that involves the
      previously mentioned species. Validation of the UCGM was done by using it to
      develop three interspecific genetic maps and by comparing genetic SSR locations
      with their physical positions on the rice pseudomolecules. In this study, we
      demonstrate that the UCGM is a useful tool for the rice genetics and breeding
      community, especially in strategies based on interspecific hybridisation.

PMID- 19847390
TI  - Optimum allocation of resources for QTL detection using a nested association
      mapping strategy in maize.
AB  - In quantitative trait locus (QTL) mapping studies, it is mandatory that the
      available financial resources are spent in such a way that the power for
      detection of QTL is maximized. The objective of this study was to optimize for
      three different fixed budgets the power of QTL detection 1 - beta* in recombinant
      inbred line (RIL) populations derived from a nested design by varying (1) the
      genetic complexity of the trait, (2) the costs for developing, genotyping, and
      phenotyping RILs, (3) the total number of RILs, and (4) the number of
      environments and replications per environment used for phenotyping. Our computer
      simulations were based on empirical data of 653 single nucleotide polymorphism
      markers of 26 diverse maize inbred lines which were selected on the basis of 100
      simple sequence repeat markers out of a worldwide sample of 260 maize inbreds to
      capture the maximum genetic diversity. For the standard scenario of costs, the
      optimum number of test environments (E (opt)) ranged across the examined total
      budgets from 7 to 19 in the scenarios with 25 QTL. In comparison, the E (opt)
      values observed for the scenarios with 50 and 100 QTL were slightly higher. Our
      finding of differences in 1 - beta* estimates between experiments with optimally
      and sub-optimally allocated resources illustrated the potential to improve the
      power for QTL detection without increasing the total resources necessary for a
      QTL mapping experiment. Furthermore, the results of our study indicated that also
      in studies using the latest genomics tools to dissect quantitative traits, it is
      required to evaluate the individuals of the mapping population in a high number
      of environments with a high number of replications per environment.

PMID- 19847391
TI  - Vrn-D4 is a vernalization gene located on the centromeric region of chromosome 5D
      in hexaploid wheat.
AB  - Natural variation in wheat requirement of long exposures to cold temperatures to
      accelerate flowering (vernalization) is mainly controlled by the Vrn-1, Vrn-2,
      Vrn-3, and Vrn-4 loci. The first three loci have been well characterized, but
      limited information is available for Vrn-4. So far, natural variation for Vrn-4
      has been detected only in the D genome (Vrn-D4), and genetic stocks for this gene
      are available in Triple Dirk (TDF, hereafter). We detected heterogeneity in the
      Vrn-1 alleles present in different TDF stocks, which may explain inconsistencies
      among previous studies. A correct TDF seed stock from Japan carrying recessive
      vrn-A1, vrn-B1, and vrn-D1 alleles was crossed with three different winter
      cultivars to generate F(2) mapping populations. Most of the variation in
      flowering time in these three populations was controlled by a single locus, Vrn
      D4, which was mapped within a 1.8 cM interval flanked by markers Xcfd78 and
      Xbarc205 in the centromeric region of chromosome 5D. A factorial ANOVA for
      heading time using Vrn-D4 alleles and vernalization as factors showed a
      significant interaction (P < 0.0001), which confirmed that the Vrn-D4 effect on
      flowering time is modulated by vernalization. Comparison of the different Triple
      Dirk stocks revealed that Vrn-B1, Vrn-D1, and Vrn-D4 all have a small residual
      response to vernalization, but Vrn-D4 differs from the other two in its response
      to short vernalization periods. The precise mapping and characterization of Vrn
      D4 presented here represent a first step toward the positional cloning of this
      gene.

PMID- 19847392
TI  - Genetic association analysis of LARS2 with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: LARS2 has been previously identified as a potential type 2
      diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant
      (minor allele frequency [MAF] 3.0%). However, this association did not achieve
      genome-wide levels of significance. The aim of this study was to establish the
      true contribution of this variant and common variants in LARS2 (MAF > 5%) to type
      2 diabetes risk. METHODS: We combined genome-wide association data (n = 10,128)
      from the DIAGRAM consortium with independent data derived from a tagging single
      nucleotide polymorphism (SNP) approach in Dutch individuals (n = 999) and took
      forward two SNPs of interest to replication in up to 11,163 Dutch participants
      (rs17637703 and rs952621). In addition, because inspection of genome-wide
      association study data identified a cluster of low-frequency variants with
      evidence of type 2 diabetes association, we attempted replication of rs9825041 (a
      proxy for this group) and the previously identified H324Q variant in up to 35,715
      participants of European descent. RESULTS: No association between the common SNPs
      in LARS2 and type 2 diabetes was found. Our replication studies for the two low
      frequency variants, rs9825041 and H324Q, failed to confirm an association with
      type 2 diabetes in Dutch, Scandinavian and UK samples (OR 1.03 [95% CI 0.95
      1.12], p = 0.45, n = 31,962 and OR 0.99 [0.90-1.08], p = 0.78, n = 35,715
      respectively). CONCLUSIONS/INTERPRETATION: In this study, the largest study
      examining the role of sequence variants in LARS2 in type 2 diabetes
      susceptibility, we found no evidence to support previous data indicating a role
      in type 2 diabetes susceptibility.

PMID- 19847393
TI  - Cell division autoantigen 1 plays a profibrotic role by modulating downstream
      signalling of TGF-beta in a murine diabetic model of atherosclerosis.
AB  - AIMS/HYPOTHESIS: Excess accumulation of vascular extracellular matrix (ECM) is an
      important pathological process in cardiovascular diseases including diabetes
      associated atherosclerosis. We explored how a recently identified molecule, cell
      division autoantigen 1 (CDA1), influences the profibrotic TGF-beta pathway
      leading to vascular ECM accumulation. METHODS: Expression levels of genes
      encoding for CDA1, TGF-beta and connective tissue growth factor (CTGF) were
      examined in aorta from Apoe(-/-) mice with or without diabetes. We used
      retroviral and adenoviral constructs to knockdown or overexpress Tspyl2, the gene
      encoding CDA1, in mouse vascular smooth muscle cells (VSMCs) with or without TGF
      beta treatment in order to demonstrate the role of CDA1 in TGF-beta signalling.
      RESULTS: In vivo studies indicated that the mRNA levels of CDA1-encoding gene
      Tspyl2 and protein levels of CDA1 were elevated in the aorta of diabetic Apoe(-/
      ) mice, accompanied by increased levels of Tgf-beta (also known as Tgfb1), Ctgf
      and ECM accumulation. In vitro studies in vascular cells showed that TGF-beta
      treatment rapidly increased CDA1 protein levels, which then amplified TGF-beta
      signalling leading to upregulation of ECM genes. Knockdown of CDA1-encoding gene
      Tspyl2 to reduce cellular CDA1 level markedly attenuated TGF-beta-stimulated MAD
      homologue 3 (drosophila; SMAD3) phosphorylation and transcriptional activities.
      CDA1 overproduction increased and Tspyl2 knockdown decreased expression of TGF
      beta receptor type I, TbetarI (also known as Tgfbr1), but not TGF-beta receptor
      type II, TbetarII (also known as Tgfbr2), providing a mechanism for CDA1's action
      in modulating TGF-beta signalling. Knockdown of CDA1-encoding gene Tspyl2 also
      blocked the profibrotic effect of TGF-beta in VSMCs. CONCLUSIONS/INTERPRETATION:
      CDA1 plays an important role in vascular ECM accumulation by amplifying TGF-beta
      signalling. This is critical for the profibrotic effect of TGF-beta in the
      vasculature. CDA1 is therefore a potential target for attenuating vascular ECM
      accumulation caused by enhanced TGF-beta action, as seen in diabetic
      atherosclerosis.

PMID- 19847394
TI  - Diabetes regulates mitochondrial biogenesis and fission in mouse neurons.
AB  - AIMS/HYPOTHESIS: Normal mitochondrial activity is a critical component of
      neuronal metabolism and function. Disruption of mitochondrial activity by altered
      mitochondrial fission and fusion is the root cause of both neurodegenerative
      disorders and Charcot-Marie-Tooth type 2A inherited neuropathy. This study
      addressed the role of mitochondrial fission in the pathogenesis of diabetic
      neuropathy. METHODS: Mitochondrial biogenesis and fission were assayed in both in
      vivo and in vitro models of diabetic neuropathy. Gene, protein, mitochondrial DNA
      and ultrastructural analyses were used to assess mitochondrial biogenesis and
      fission. RESULTS: There was greater mitochondrial biogenesis in dorsal root
      ganglion neurons from diabetic compared with non-diabetic mice. An essential step
      in mitochondrial biogenesis is mitochondrial fission, regulated by the
      mitochondrial fission protein dynamin-related protein 1 (DRP1). Evaluation of
      diabetic neurons in vivo indicated small, fragmented mitochondria, suggesting
      increased fission. In vitro studies revealed that short-term hyperglycaemic
      exposure increased levels of DRP1 protein. The influence of hyperglycaemia
      mediated mitochondrial fission on cell viability was evaluated by knockdown of
      Drp1 (also known as Dnm1l). Knockdown of Drp1 resulted in decreased
      susceptibility to hyperglycaemic damage. CONCLUSIONS/INTERPRETATION: We propose
      that: (1) mitochondria undergo biogenesis in response to hyperglycaemia, but the
      increased biogenesis is insufficient to accommodate the metabolic load; (2)
      hyperglycaemia causes an excess of mitochondrial fission, creating small, damaged
      mitochondria; and (3) reduction of aberrant mitochondrial fission increases
      neuronal survival and indicates an important role for the fission-fusion
      equilibrium in the pathogenesis of diabetic neuropathy.

PMID- 19847395
TI  - Relationship between fractional pancreatic beta cell area and fasting plasma
      glucose concentration in monkeys.
AB  - AIMS/HYPOTHESIS: We sought to establish the relationship between fasting plasma
      glucose concentrations and pancreatic fractional beta cell area in adult
      cynomolgus monkeys (Macaca fascicularis). METHODS: Fasting plasma glucose and
      pancreatic fractional beta cell area were measured in 18 control and 17
      streptozotocin-treated adult primates (17.0 +/- 1.2 vs 15.4 +/- 1.2 years old).
      RESULTS: Fasting plasma glucose was increased (12.0 +/- 2.0 vs 3.4 +/- 0.1
      mmol/l, p < 0.01) and fractional beta cell area was decreased (0.62 +/- 0.13% vs
      2.49 +/- 0.35%, p < 0.01) in streptozotocin-treated monkeys. The relationship
      between fasting plasma glucose and pancreatic fractional beta cell area was
      described by a wide range of beta cell areas in controls. In streptozotocin
      treated monkeys there was an inflection of fasting blood glucose at approximately
      50% of the mean beta cell area in controls with a steep increase in blood glucose
      for each further decrement in beta cell area. CONCLUSIONS/INTERPRETATION: In
      adult non-human primates a decrement in fractional beta cell area of
      approximately 50% or more leads to loss of glycaemic control.

PMID- 19847396
TI  - Moderate hypothermia with intracranial pressure monitoring as a therapeutic
      paradigm for the management of acute liver failure: a systematic review.
AB  - OBJECTIVE: To systematically review the literature and present data on the safety
      and efficacy of induced moderate hypothermia combined with ICP monitoring in
      critically ill patients with acute liver failure. DESIGN: We conducted a
      retrospective observational search of MEDLINE database using both OVID and PubMed
      with the following MeSH terms, "Hypothermia, Induced," "Brain Edema,"
      "Intracranial Hypertension" (ICH), "Liver failure, Acute" and "Liver Failure,
      Fulminant." We limited our search to case series involving at least three human
      subjects and all other clinical trials. Baseline ICP, cerebral perfusion pressure
      (CPP) and cerebral blood flow (CBF) as well as the response of these variables to
      hypothermia were recorded when available. Additional clinical and demographic
      data were also recorded. RESULTS: Five case series were identified. Pre-existing
      coagulopathy from liver failure was reversed by various modalities in all studies
      prior to insertion of ICP monitors. Induction of moderate hypothermia combined
      with ICP monitoring consistently improved ICP, CPP and CBF in four trials; one
      trial demonstrated the feasibility and effectiveness of moderate induced
      hypothermia as part of a protocolized strategy for the management of ICH.
      CONCLUSIONS: Limited data exist concerning the safety and efficacy of moderate
      hypothermia and ICP monitoring for the treatment of ICH in acute liver failure.
      The available evidence shows that induction of moderate hypothermia in this
      clinical setting is feasible and possibly efficacious. Well-designed prospective
      clinical trials are warranted in this challenging context, given the potential of
      providing a bridge to liver transplantation or even clinical recovery.

PMID- 19847397
TI  - F-18-fluorodeoxyglucose positron emission tomography combined with CT in
      critically ill patients with suspected infection.
AB  - PURPOSE: To assess the value of F-18-fluorodeoxyglucose positron emission
      tomography (FDG-PET) combined with CT in critically ill patients suspected of
      having an infection. METHODS: FDG-PET CT scans requested for evaluation of a
      suspected infection or inflammatory process in critically ill, mechanically
      ventilated patients were analyzed (blinded for the final clinical diagnosis) and
      compared with clinical follow-up. RESULTS: Thirty-five FDG-PET/CT scans performed
      in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month
      72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three
      FDG-PET/CT scans were considered false positive, in one case leading to
      additional diagnostic procedures (specificity 79%). Additionally, 11 true
      negatives were found (sensitivity 100%), leading to an overall accuracy of 91%.
      CONCLUSIONS: FDG-PET/CT scanning is of additional value in the evaluation of
      suspected infection in critically ill patients in whom conventional diagnostics
      did not lead to a diagnosis. Apart from the high accuracy, in this study it
      appeared that, in addition to conventional diagnostic techniques that were
      routinely performed, a normal FDG-PET/CT ruled out important infections requiring
      prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly
      metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is
      not suited to detect infections in these tissues.

PMID- 19847398
TI  - Incidence and prognosis of dysnatremias present on ICU admission.
AB  - PURPOSE: Dysnatremias are common in patients admitted to the intensive care unit
      (ICU). Whether the presence of disorders of sodium balance on ICU admission is
      independently associated with excess mortality is unknown. We hypothesized that
      dysnatremias at the time of ICU admission are independent risk factors for
      increased mortality in critically ill patients. METHODS: We conducted a
      retrospective study in 77 medical, surgical, and mixed ICUs in Austria, with a
      database of 151,486 adults admitted consecutively over a period of 10 years (1998
      2007). RESULTS: Most patients (114,170, 75.4%) had normal sodium levels (135 < or
      = Na < or = 145 mmol/L) on ICU admission. The frequencies of borderline (130 < or
      = Na < 135 mmol/L), mild (125 < or = Na < 130 mmol/L), and severe hyponatremia
      (Na < 125 mmol/L) were 13.8%, 2.7%, and 1.2%, respectively. The frequencies of
      borderline (145 < Na < or = 150 mmol/L), mild (150 < Na < or = 155 mmol/L), and
      severe hypernatremia (Na > 155 mmol/L) were 5.1%, 1.2%, and 0.6%, respectively.
      All types and grades of dysnatremia were associated with increased raw and risk
      adjusted hospital mortality ratios. Multiple logistic regression analysis showed
      an independent mortality risk rising with increasing severity of both
      hyponatremia and hypernatremia. Odds ratios and 95% confidence interval (CI) for
      borderline, mild, and severe hyponatremia were 1.32 (1.25-1.39), 1.89 (1.71
      2.09), and 1.81 (1.56-2.10), respectively. Odds ratios and 95% CI for borderline,
      mild, and severe hypernatremia were 1.48 (1.36-1.61), 2.32 (1.98-2.73), and 3.64
      (2.88-4.61), respectively. CONCLUSIONS: Our results suggest that both hypo- and
      hypernatremia present on admission to the ICU are independent risk factors for
      poor prognosis.

PMID- 19847399
TI  - The bispectral index and suppression ratio are very early predictors of
      neurological outcome during therapeutic hypothermia after cardiac arrest.
AB  - PURPOSE: To evaluate the bispectral index (BIS) and suppression ratio (SR) as
      very early predictors of neurological outcome during therapeutic hypothermia
      after cardiac arrest. METHODS: Demographic data, BIS1, and SR1 were recorded from
      97 patients after the first dose of neuromuscular blockade, with outcomes
      blinded, and compared to the discharge Cerebral Performance Category (CPC).
      Receiver-operator characteristic curves and a multiple logistic regression model
      were constructed to predict good (CPC 1-2, GO) and poor (CPC 3-5, PO)
      neurological outcomes. RESULTS: Fourteen patients were excluded from the final
      analysis; 33 of the remaining 83 patients (40%) were classified as GO. The BIS1
      was higher in patients with GO (37 [28-40] vs. 7 [3-15], p < 0.001). BIS1 < 22
      predicted PO with a likelihood ratio (LR) of 14.2 and an area under the curve
      (AUC) of 0.91 (95% CI 0.85-0.98, p < 0.001). SR1 > or =48 predicted PO with a LR
      of 12.7 and an AUC of 0.90 (95% CI 0.83-0.98, p < 0.001). Both BIS1 (DeltaAUC
      0.16, p = 0.006) and SR1 (DeltaAUC 0.16, p = 0.005) predicted outcomes better
      than the time to return of spontaneous circulation. CONCLUSIONS: In our single
      center cohort utilizing moderate sedation, the bispectral index and suppression
      ratio recorded after the first dose of intermittent neuromuscular blockade were
      accurate and very early predictors of neurological outcome during therapeutic
      hypothermia after cardiac arrest.

PMID- 19847400
TI  - The influence of the airway driving pressure on pulsed pressure variation as a
      predictor of fluid responsiveness.
AB  - OBJECTIVE: Assessing pulse pressure variation (PPV) to predict fluid
      responsiveness in mechanically ventilated patients with tidal volume (VT) and the
      impact of VT and airway driving pressure (P(plat) - PEEP) on the ability of PPV
      for predicting fluid responsiveness. DESIGN: Prospective interventional study.
      SETTING: ICU of a university hospital. PATIENTS: Fifty-seven mechanically
      ventilated and sedated patients with acute circulatory failure requiring cardiac
      output (CO) measurement. INTERVENTION: Fluid challenge was given in patients with
      signs of hypoperfusion (oliguria <0.5 ml kg(-1) h(-1), attempt to decrease
      vasopressor infusion rate). Fluid responsiveness was defined as an increase in
      the stroke index (SI) >or=15%. Receiver-operating characteristic (ROC) curves
      were generated for PPV and central venous pressure (CVP). RESULTS: The stroke
      index was increased >or=15% in 41 patients (71%). At baseline, CVP was lower and
      PPV was higher in responders. The areas under the ROC curves of PPV and CVP were
      0.77 (95% CI 0.65-0.90) and 0.76 (95% CI 0.64-0.89), respectively (P = 0.93). The
      best cutoff values of PPV and CVP were 7% and 9 mmHg, respectively. In 30 out of
      41 responders, PPV was <13%. Using a polytomic logistic regression (P(plat)-
      PEEP) was the sole independent factor associated with a PPV value <13% in
      responders. In these responders, (P(plat)--PEEP) was <or=20 cmH(2)O. CONCLUSION:
      In patients mechanically ventilated with low VT, PPV values <13% do not rule out
      fluid responsiveness, especially when (P(plat)--PEEP) is <or=20 cmH(2)O.

PMID- 19847401
TI  - Simultaneous bilateral anterior cruciate ligament reconstruction: a safe option.
AB  - When patients present with bilateral anterior cruciate ligament (ACL) deficiency
      and require reconstruction in both knees, a single setting or staged approach can
      be adopted. Although single-setting reconstruction has been described, there are
      no published case series that describe simultaneous bilateral ACL reconstruction.
      We report a case series of eight patients who underwent simultaneous bilateral
      ACL reconstruction. We used two-camera stack systems to allow for truly
      simultaneous bilateral surgery by two surgical teams. At 2 weeks, all patients
      were independent in mobility. There was no difference in pivot shift, Lysholm and
      Tegner scores at 1 year when compared to published outcomes for unilateral ACL
      reconstruction. The median duration of follow-up was 28 months (range 12-50
      months). Based on these small numbers, our results demonstrate that simultaneous
      bilateral ACL reconstruction is a safe and clinically effective option when using
      either hamstring or patella tendon graft.

PMID- 19847402
TI  - A computerized analysis of femoral condyle radii in ACL intact  and contralateral
      ACL reconstructed knees using 3D CT.
AB  - The bony geometry of the distal femoral condyles may have a significant influence
      on knee joint kinematics. The aim of this study was to analyze the relationship
      between the size of the medial and lateral femoral condyles in different planes.
      Seventy-four three dimensional (3D) CT reconstructions of 37 patients with ACL
      intact and contralateral ACL reconstructed knees were used and the data were
      imported into a graphical software program. The radii of the medial and lateral
      femoral condyles were analyzed in the sagittal, coronal, and axial planes by
      digitally reconstructed circular arcs along the bony condylar profiles marked
      with multiple digital surface points. Intra- and interobserver testing was
      performed. In the intact knees the average sagittal radius of the distal medial
      and lateral femoral condyles was similar. There was a significant difference
      between the radii of the distal medial femoral condyles compared to lateral
      femoral condyles in the coronal plane (22.4 vs. 27.8 mm, P < 0.001) as well as
      between the radii of the medial femoral condyles in the axial plane in 90 knee
      flexion compared to the lateral femoral condyles (21.3 vs. 18.3 mm, P < 0.001).
      The average radius of the medial femoral condyles was significantly smaller in
      extension compared to 90 of flexion (21.2 vs. 22.4 mm, P = 0.05) and the average
      radius of the lateral femoral condyles was significantly larger in extension
      compared to 90 of flexion (27.8 vs. 18.3 mm, P < 0.001). The 37 ACL reconstructed
      knees demonstrated similar radii in all three planes when compared to the intact
      knees without any significant difference. The described method of assessing the
      architecture of the distal femoral condyles is non-invasive, reproducible, and
      provides reliable geometric parameters necessary for the 3D reconstruction of the
      femoral geometry in vivo. The radii of the FC were similar in the sagittal planes
      but demonstrate a significant asymmetry in the axial and coronal planes. The
      average radius of the lateral femoral condyles was significantly larger in
      extension whereas the radius of the medial femoral condyles was significantly
      larger in flexion. We did not find any significant difference in the shape of the
      femoral condyles in ACL intact and contralateral ACL reconstructed knees
      indicating that the geometry of the femoral condyles might not influence the
      injury mechanism of ACL rupture. The asymmetry between the femoral condyles may
      be considered when designing new anatomical femoral components in knee
      arthroplasty.

PMID- 19847403
TI  - How to avoid the risk of intraoperative cartilage damage   in anatomic four
      tunnel double bundle anterior cruciate   ligament reconstruction.
AB  - Double bundle (DB) anterior cruciate ligament (ACL) reconstruction is technically
      demanding. In order to create four anatomical anteromedial (AM) and
      posterolateral (PL) bone tunnels many surgeons adopt new ways of tibial and
      femoral bone tunnel drilling. From surgical experience, these technical changes
      might increase the risk for intraoperative pitfalls. An intraoperative articular
      cartilage damage to the medial femoral condyle or the medial tibial plateau could
      be disastrous for the patient. It may be caused by an insufficient anteromedial
      portal technique for femoral AM and PL bone tunnel drilling or flat tibial AM or
      PL bone tunnel reaming. Potential pitfalls may be avoided by small modifications
      to the surgical technique. In this present technical note, a sequence of surgical
      steps are described, which may help to avoid articular cartilage damage to the
      medial femoral condyle and medial tibial plateau in anatomical four tunnel DB ACL
      reconstruction.

PMID- 19847404
TI  - Comparison of two minimally invasive implantation instrument-sets for total knee
      arthroplasty.
AB  - Several choices of instrument systems are available for minimally invasive
      surgical approaches. There are reports that one alternative, the quadriceps
      sparing, side-cutting instrumentation, results in diminished implantation
      accuracy. A total of 108 patients were randomized to undergo TKA either using
      side-cutting implant instrumentation (Group A) or anterior-posterior mini
      incision instrumentation (Group B). All TKAs were operated on with a minimal
      invasive, mini-midvastus surgical approach. 50% of the TKAs were performed with
      computer-assistance in each cohort. The radiographic parameters, clinical
      outcomes and knee scores were evaluated preoperatively and 3 months
      postoperative. In Group B, we found significantly higher accuracy for the
      mechanical axis of the limb (range +/-3 degrees: Group A 54% versus Group B 89%,
      p = <0.001), medial proximal tibial angle (range +/-3 degrees: Group A 85% versus
      Group B 98%, p = <0.027) and tibial slope (range +/-3 degrees: Group A 59% versus
      Group B 85%, p = <0.007). The application of the navigation system could only
      significantly reduce outliers (accuracy >3 degrees) in Group B. Clinical outcomes
      and knee scores were similar in both groups and were not influenced by computer
      assistance. Using the anterior-posterior, mini-incision instruments for minimally
      invasive TKA will lead to higher implantation accuracy when compared to the
      quadriceps sparing side-cutting instrumentation. The navigation technique could
      not compensate for shortcomings of the side-cutting instrumentation. The clinical
      relevance of this study is that the quadriceps sparing side-cutting
      instrumentation should not be used for TKA because of unacceptable reduced
      implantation accuracy.

PMID- 19847406
TI  - GC-MS analysis of low-molecular-weight dicarboxylic acids in atmospheric aerosol:
      comparison between silylation and esterification derivatization procedures.
AB  - This paper describes methods for the determination of low-molecular-weight (LMW)
      dicarboxylic acids in atmospheric aerosols as important chemical tracers for
      source apportionment of aerosol organics and for studying atmospheric processes
      leading to secondary organic aerosol formation. The two derivatization procedures
      most widely used in GC analysis of dicarboxylic acids were compared:
      esterification using BF(3)/alcohol reagent and silylation using N,O
      bis(trimethylsilyl)-trifluoroacetamide (BSTFA). The advantages and drawbacks of
      the two methods are investigated and compared in terms of (1) precision and
      accuracy of the results and (2) sensitivity and detection limit of the procedure.
      The comparative investigation was performed on standard solutions containing
      target C(3)-C(9) dicarboxylic acids and on experimental particulate matter (PM)
      samples. Attention was focused on low-volume sampling devices that collect small
      amounts of sample for organic speciation. The results show that, overall, both
      the techniques appear suitable for the analysis of LMW dicarboxylic acids in
      atmospheric aerosols since they provide low detection limits (< or = 4 ng m(-3))
      and satisfactory reproducibility (RSD% < or = 15%). Between them, BSTFA should be
      the reagent of choice under the most limiting conditions of PM filters collected
      by low-volume air samplers: It provides determination of all the target C(3)-C(9)
      dicarboxylic acids with lower detection limits (< or = 2 ng m(-3)) and higher
      reproducibility (RSD% < or = 10%).

PMID- 19847405
TI  - Effects of mGluR1 antagonism in the dorsal hippocampus on drug context-induced
      reinstatement of cocaine-seeking behavior in rats.
AB  - RATIONALE: The functional integrity of the dorsal hippocampus (DH) is necessary
      for drug context-induced reinstatement of cocaine seeking. However, the
      neuropharmacological mechanisms of this phenomenon are poorly understood.
      OBJECTIVES: Given the known significance of group I metabotropic glutamate
      receptors (mGluRs), including the mGluR1 subtype, in drug-induced behaviors, the
      present study was designed to evaluate the contribution of mGluR1s in the DH to
      drug context-induced reinstatement of extinguished cocaine-seeking behavior.
      METHODS: Sprague-Dawley rats were trained to lever press for unsignaled cocaine
      infusions in a distinct environmental context (cocaine-paired context) followed
      by extinction training in a distinctly different environmental context
      (extinction context). Using a counterbalanced partial within-subjects testing
      design, rats were re-exposed to the cocaine-paired context or the extinction
      context while cocaine-seeking behavior (nonreinforced active lever pressing) was
      assessed. Prior to each test session, rats received bilateral microinfusions of
      the highly potent mGluR1-selective antagonist JNJ16259685 (0.6, 30, or 120 pg/0.5
      microl per hemisphere) or vehicle into the DH or the overlying somatosensory
      cortex trunk region (SStr; anatomical control). RESULTS: Intra-DH, but not intra
      SStr, JNJ16259685 infusions dose dependently attenuated drug context-induced
      reinstatement of cocaine seeking relative to vehicle treatment, without
      attenuating instrumental behavior in the extinction context, general motor
      activity, or food-reinforced instrumental behavior in control experiments.
      CONCLUSIONS: Stimulation of mGluR1s in the DH is necessary for incentive
      motivational and/or memory processes that contribute to drug context-induced
      cocaine-seeking behavior. These findings indicate that the mGluR1 is an
      interesting target from an addiction treatment perspective.

PMID- 19847407
TI  - How and when auditory action effects impair motor performance.
AB  - Music performance is characterized by complex cross-modal interactions, offering
      a remarkable window into training-induced long-term plasticity and multimodal
      integration processes. Previous research with pianists has shown that playing a
      musical score is affected by the concurrent presentation of musical tones. We
      investigated the nature of this audio-motor coupling by evaluating how congruent
      and incongruent cross-modal auditory cues affect motor performance at different
      time intervals. We found facilitation if a congruent sound preceded motor
      planning with a large Stimulus Onset Asynchrony (SOA -300 and -200 ms), whereas
      we observed interference when an incongruent sound was presented with shorter
      SOAs (-200, -100 and 0 ms). Interference and facilitation, instead of developing
      through time as opposite effects of the same mechanism, showed dissociable time
      courses suggesting their derivation from distinct processes. It seems that the
      motor preparation induced by the auditory cue has different consequences on motor
      performance according to the congruency with the future motor state the system is
      planning and the degree of asynchrony between the motor act and the sound
      presentation. The temporal dissociation we found contributes to the understanding
      of how perception meets action in the context of audio-motor integration.

PMID- 19847408
TI  - The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics
      and pharmacodynamics of glipizide in Chinese subjects.
AB  - OBJECTIVE: To study the effects of CYP2C9 and CYP2C19 genetic polymorphisms on
      the pharmacokinetics and pharmacodynamics of glipizide. METHODS: Eighteen healthy
      male subjects were divided into three groups according to their genotypes: group
      I, CYP2C9*1/*1 and CYP2C19 extensive metabolizers (EMs); group II, CYP2C9*1/*1
      and CYP2C19 poor metabolizers (PMs); and group III, CYP2C9*1/*3 and CYP2C19 EMs.
      After a single dose of a 5-mg glipizide tablet, plasma concentrations of
      glipizide for a 36-h period were determined. Meanwhile, plasma glucose levels and
      plasma insulin levels were determined from 0 to 4 h after dosing. RESULTS: The
      area under the plasma concentration-time curve (AUC(0-infinity)) was 2.0-fold
      higher and the oral clearance was 51.1% lower in group III than in group I. The
      change in fasting insulin level within 1 h (DeltaAUEC(insulin0-1h)) in group III
      was 3.8-fold higher than that in group I. The glipizide parameters in group II
      exhibited similar tendencies to those in group III. CONCLUSIONS: These results
      suggest that CYP2C9 polymorphism significantly influences the pharmacokinetics
      and pharmacodynamics of glipizide, which needs to be considered in clinical
      practice. CYP2C19 polymorphism exhibits a tendency to influence the effects of
      glipizide, to a certain extent similarly to CYP2C9 polymorphism.

PMID- 19847411
TI  - Gymnastics injuries and imaging in children.
AB  - Injuries of children participating in gymnastics are seen less often than in more
      popular sports. Patterns of injury are predictable based upon sex, age and level
      of intensity of training and competition. More injuries are seen in girls than in
      boys, and the great majority of early adolescents who compete have wrist pain.
      Some otherwise quiescent congenital spine anomalies may be uncovered by the
      stress of gymnastics maneuvers and present with low back pain. In addition to
      diagnosis of injuries, imaging can be used to guide analgesic and anti
      inflammatory therapy in some injured athletes. Parents whose children wish to
      participate in gymnastics should understand that fewer injuries occur in the
      child enjoying recreational gymnastics than in competing gymnasts. More
      gymnastics injuries are found in very competitive athletes training at higher
      levels.

PMID- 19847409
TI  - Detection of changes in cerebrospinal fluid space in idiopathic normal pressure
      hydrocephalus using voxel-based morphometry.
AB  - INTRODUCTION: We attempted to detect alterations in the cerebrospinal fluid (CSF)
      space in patients with idiopathic normal pressure hydrocephalus (iNPH) using
      voxel-based morphometry (VBM). METHODS: We obtained sagittal volume images of the
      entire head by three-dimensional T1-weighted magnetic resonance imaging and
      compared the regional distribution of CSF in 12 patients with iNPH, 14 patients
      with Alzheimer's disease (AD), and 17 healthy individuals using VBM with
      automatically extracted CSF objects. RESULTS: VBM demonstrated significant
      widening at the lateral ventricles and Sylvian fissures and narrowing of the CSF
      space at the high convexity/midline areas in iNPH patients, compared to the AD
      patients and healthy controls (p < 0.05, after correction with a false-discovery
      rate). In addition, the ratio of the CSF volume in the lateral ventricle/Sylvian
      fissure area to that in the high convexity/midline area in iNPH patients (3.9 +/-
      1.2) was remarkably greater than that in AD patients (1.2 +/- 0.3) and controls
      (0.9 +/- 0.3; one-way ANOVA, p < 0.001; post hoc Tukey's test, p < 0.001); we
      could discriminate iNPH patients from those in the other two groups without any
      overlap, when using a cutoff level of 1.9. CONCLUSION: VBM using CSF objects can
      be used to delineate the characteristic alteration of the CSF space in iNPH
      patients, which has been evaluated by visual interpretation.

PMID- 19847412
TI  - Introduction to the minisymposium on sports imaging in children.

PMID- 19847413
TI  - MR imaging of overuse injuries in the skeletally immature gymnast: spectrum of
      soft-tissue and osseous lesions in the hand and wrist.
AB  - BACKGROUND: In the pediatric gymnast, stress-related physeal injuries have been
      well described with characteristic imaging findings. However, a spectrum of
      overuse injuries, some rarely reported in the literature, can be encountered in
      the gymnast's hand and wrist. OBJECTIVE: To demonstrate the MR appearance of a
      spectrum of overuse injuries in the skeletally immature wrist and hand of
      pediatric gymnasts. MATERIALS AND METHODS: A total of 125 MR exams of the hand
      and wrist in skeletally immature children were performed at our institution
      during a 2-year period. Clinical histories were reviewed for gymnastics
      participation. MR studies of that subpopulation were reviewed and abnormalities
      tabulated. RESULTS: Of the MR studies reviewed, ten gymnasts were identified, all
      girls age 12-16 years (mean age 14.2 years) who presented with wrist or hand
      pain. Three of these children had bilateral MR exams. Abnormalities included
      chronic physeal injuries in three children. Two girls exhibited focal lunate
      osteochondral defects. Triangular fibrocartilage tears were present in three
      girls, one of whom had a scapholunate ligament tear. Two girls manifested
      metacarpal head flattening and necrosis. CONCLUSION: A variety of soft-tissue and
      osseous lesions can be encountered in the skeletally immature gymnast.
      Familiarity with these stress-related injuries is important for accurate
      diagnosis.

PMID- 19847414
TI  - Neonatal diagnosis of congenital pseudarthrosis of the clavicle.

PMID- 19847415
TI  - Parenchymal and pleural abnormalities in children with and without pulmonary
      embolism at MDCT pulmonary angiography.
AB  - BACKGROUND: Prior studies in adults suggest that a wedge-shaped peripheral
      consolidation may be predictive of pulmonary embolism (PE). In contrast, a
      previous study in children provided no evidence of an association between this
      finding and PE, but it was limited by a small sample size and was not
      specifically designed to answer this question. OBJECTIVE: To compare the
      frequencies of parenchymal and pleural abnormalities in children with and without
      PE at multidetector computed tomographic pulmonary angiography (CTPA). MATERIALS
      AND METHODS: The study population included 22 consecutive pediatric patients (11
      males, 11 females; mean age 13.2 +/- 5.8 years; range 4 months to 18 years) with
      PE diagnosed by CTPA from July 2004 to January 2009 and identified using our
      hospital database. The comparison group included 22 randomly selected pediatric
      patients (10 males, 12 females; mean age 15.2 +/- 3.3 years; range 5.6 to 18
      years) who underwent CTPA studies without evidence of PE during the same study
      period. All CTPA studies were reviewed by consensus by two pediatric radiologists
      for the presence of parenchymal and pleural abnormalities including: wedge-shaped
      peripheral consolidation, other forms of consolidation, atelectasis, linear
      opacity, ground-glass opacity, mosaic attenuation pattern, nodule, mass, focal
      patchy increased attenuation, and pleural effusion. Differences in frequencies of
      parenchymal and pleural abnormalities between the two groups were analyzed by
      logistic regression to determine odds ratios for association with PE. The two
      groups were also compared with respect to risk factors for PE. RESULTS: Wedge
      shaped peripheral consolidation was seen in eight children (36%) with PE and in
      two children (9%) without PE [odds ratio = 5.7, 95% confidence interval (CI): 1.2
      to 30, p = 0.03]. There were no significant differences in the frequency of other
      findings between the groups (all p-values > 0.10). Prior history of neoplasm was
      the only independent risk factor significantly associated with the presence of PE
      (p = 0.006). CONCLUSION: Wedge-shaped peripheral consolidation is significantly
      associated with PE on CTPA studies of children. The identification of a wedge
      shaped peripheral consolidation in children should alert radiologists to
      carefully evaluate for concurrent PE.

PMID- 19847416
TI  - Soccer injuries in children.
AB  - Soccer is the most popular sport in the world, with FIFA recognising more than
      265 million amateur players. Despite the fact that soccer is a contact sport, it
      is perceived to be relatively safe to play, a factor that has contributed to its
      status as the fastest growing team sport in the USA. Acute and minor injuries
      predominate in the statistics, with contusions and abrasions being the most
      commonly recorded. As would be expected, the majority of soccer injuries are to
      the lower limbs, with serious truncal and spinal trauma being rare. This article
      examines the type and anatomic location of injuries sustained by children and
      adolescents who play soccer, and the main mechanisms whereby such injuries occur.
      The risk factors underpinning injury occurrence are considered, along with injury
      avoidance tactics.

PMID- 19847417
TI  - Vesicovaginal reflux: recognition and diagnosis using ultrasound.
AB  - BACKGROUND: Vaginal reflux is a functional voiding disorder seen in prepubertal
      girls without anatomical or neurological abnormality. When not associated with
      urinary tract infections (UTI), asymptomatic bacteriuria, post-void dribbling or
      daytime enuresis it may be considered a normal finding. OBJECTIVE: To review the
      radiographic features of vesicovaginal reflux based on multiple imaging
      modalities. MATERIALS AND METHODS: Three girls aged 11, 13 and 5 years were
      referred for pelvic US for daytime incontinence, post-void dribbling, frequency
      and urgency. One girl also had recurrent UTIs treated with antibiotics and was
      investigated for vesicoureteric reflux with US and voiding cystourethrogram
      (VCUG). All three were examined with MRI. RESULTS: Imaging appearance common to
      all three girls was a fluid-filled mass posterior to the bladder that disappeared
      after voiding. A previous VCUG in one girl had shown contrast medium refluxing
      into the vagina which disappeared after bladder emptying. Pelvic MRI confirmed
      the findings in all three girls. CONCLUSION: US examination of a distended
      bladder followed by a post-void study easily provides the correct diagnosis of
      vesicovaginal reflux by identifying the vagina as the fluid-filled mass.
      Treatment involves behavioural modifications. Though well known to urologists,
      this may be a perplexing pathology for the inexperienced trainee radiologist.

PMID- 19847418
TI  - 1H-MRS for the diagnosis of acute disseminated encephalomyelitis: insight into
      the acute-disease stage.
AB  - BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a demyelinating
      disorder of the central nervous system (CNS). Differentiating ADEM from other
      inflammatory disorders, such as multiple sclerosis, is not always conclusive
      using conventional MRI. OBJECTIVE: To evaluate longitudinal magnetic resonance
      spectroscopy (MRS) changes that distinguish ADEM from other inflammatory
      disorders. MATERIALS AND METHODS: MRI/MRS scans were performed in seven patients
      with ADEM during the acute and chronic phases of the disease. RESULTS: Partial
      recovery was detected between the acute and chronic phases in choline/creatine
      ratio. Major elevation of lipids and reduction in myo-inositol/creatine ratio was
      detected in all patients during the acute phase, followed by a reduction in
      lipids peak and elevation above normal in myo-inositol/creatine ratio during the
      chronic phase. CONCLUSION: Consistent and unique MRS changes in metabolite ratios
      between the acute and chronic presentations of the disease were found. To the
      best of our knowledge, these patterns have not been described in other
      inflammatory disorders and might assist in the early diagnosis of ADEM.

PMID- 19847421
TI  - Structural and dynamic properties of juxta-membrane segments of caveolin-1 and
      caveolin-2 at the membrane interface.
AB  - Caveolins (cav1-3) are essential membrane proteins found in caveolae. The
      caveolin scaffolding domain of cav-1 includes a short sequence containing a CRAC
      motif (V94TKYWFYR101) at its C-terminal end. To investigate the role of this
      motif in the caveolin-membrane interaction at the atomic level, we performed a
      detailed structural and dynamics characterization of a cav-1(V94-L102)
      nonapeptide encompassing this motif and including the first residue of cav-1
      hydrophobic domain (L102), in dodecylmaltoside (DM) or dodecylphosphocholine
      (DPC) micelles, as membrane mimics. Cav-1(V94-L102) partitioned better in DPC and
      in DM/anionic lipid micelles than in DM micelles, as shown by fluorescence
      titration and CD. NMR data revealed that this peptide folded as an amphipathic
      helix located in the polar head group region of DPC micelles. The two tyrosine
      side-chains, flanked by arginine and lysine residues, are situated on one face of
      this helix, whereas the phenylalanine and tryptophan side-chains are located on
      the opposite face. Fluorescence studies showed significant Trp subnanosecond
      rotations, the presence of several rotamers, and a heterogeneous location within
      the water/micelle interface. NMR studies of the shorter cav-1(V94-R101) peptide
      and of the homologous sequence of cav-2(I79SKYVMYKF87) allowed the description of
      the effect of L102 and of the amino acid variations occurring in cav-2 on the
      structure and localization in DPC micelles. Based on the topological model of
      caveolins, our results suggest that the cav-1 and cav-2 nonapeptides studied form
      interfacial alpha-helix membrane anchors in which the K/RhhhYK/Rh motif, also
      found in cav-3, may play a significant role.

PMID- 19847422
TI  - Characterisation of hexane-degrading microorganisms in a biofilter by stable
      isotope-based fatty acid analysis, FISH and cultivation.
AB  - The hexane-degrading bacterial community of a biofilter was characterised by a
      combination of stable isotope-based phospholipid fatty acid analyses,
      fluorescence in situ hybridisation and cultivation. About 70 bacterial strains
      were isolated from a full-scale biofilter used for treatment of hexane containing
      waste gas of an oil mill. The isolation approach led to 16 bacterial groups,
      which were identified as members of the Alpha-, Beta- and Gammaproteobacteria,
      Actinobacteria and Firmicutes. Three groups showed good growth on hexane as the
      sole source of carbon. These groups were allocated to the genera Gordonia and
      Sphingomonas and to the Nevskia-branch of the Gammaproteobacteria. Actively
      degrading populations in the filter material were characterised by incubation of
      filter material samples with deuterated hexane and subsequent phospholipid fatty
      acid analysis. Significant labelling of the fatty acids 16:1 cis10, 18:1 cis9 and
      18:0 10methyl affiliated the hexane-degrading activity of the biofilter with the
      isolates of the genus Gordonia. In vitro growth on hexane and in situ labelling
      of characteristic fatty acids confirmed the central role of these organisms in
      the hexane degradation within the full-scale biofilter.

PMID- 19847423
TI  - Spaceflight and modeled microgravity effects on microbial growth and virulence.
AB  - For unsuspecting bacteria, the difference between life and death depends upon
      efficient and specific responses to various stressors. Facing a much larger
      world, microbes are invariably challenged with ever-changing environments where
      temperature, pH, chemicals, and nutrients are in a constant state of flux. Only
      those that are able to rapidly reprogram themselves and express subsets of genes
      needed to overcome the stress will survive and outcompete neighboring microbes.
      Recently, low shear stress, emulating microgravity (MG) experienced in space, has
      been characterized in a number of microorganisms including fungi and prokaryotes
      ranging from harmless surrogate organisms to bona fide pathogens. Interestingly,
      MG appears to induce a plethora of effects ranging from enhanced pathogenicity in
      several Gram-negative enterics to enhanced biofilm formation. Furthermore, MG
      exposed bacteria appeared better able to handle subsequent stressors including:
      osmolarity, pH, temperature, and antimicrobial challenge while yeast exhibited
      aberrant budding post-MG-exposure. This review will focus on MG-induced
      alterations of virulence in various microbes with the emphasis placed on
      bacteria.

PMID- 19847424
TI  - Multimer technologies for detection and adoptive transfer of antigen-specific T
      cells.
AB  - Identification and purification of antigen-specific T cells without altering
      their functional status are of high scientific and clinical interest. Staining
      with major histocompatibility complex (MHC)-peptide multimers constitutes a very
      powerful method to study antigen-specific T-cell subpopulations, allowing their
      direct visualization and quantification. MHC-peptide multimers, such as dimers,
      tetramers, pentamers, streptamers, dextramers and octamers have been used to
      evaluate the frequency of CD8(+) T cells, specific for tumor/leukemia-associated
      antigens as well as for viral antigens, e.g., CMVpp65 and EBV-EBNA. Moreover, MHC
      peptide multimers have been used for rapid and efficient ex vivo isolation and
      expansion of T cells. A recent development in the field of MHC-peptide multimers
      led to the purification of CD8(+) T cells specific for leukemia antigens. This
      might help to select leukemia-specific donor lymphocyte infusions (DLIs), thus
      allowing dissection of the noxious graft-versus-host disease (GvHD) from
      beneficial anti-viral and even anti-leukemic effects. This review covers
      different types of MHC-peptide multimers and their applications, as well as the
      impact that multimers might have on further development of DLIs.

PMID- 19847425
TI  - Phase II study of fixed dose rate gemcitabine as radiosensitizer for newly
      diagnosed glioblastoma multiforme.
AB  - PURPOSE: In order to evaluate the activity of gemcitabine as radiosensitizer for
      newly diagnosed glioblastoma multiforme (GBM), a prospective single-center phase
      II study was conducted. METHODS: Eligible patients were required to have
      histologically proven GBM with evaluable and/or measurable disease after surgery.
      They were treated by standard cranial irradiation plus concomitant fixed dose
      rate gemcitabine given intravenously at 175 mg/m(2) weekly for 6 weeks. After
      chemo-radiotherapy, irrespective of tumor response, patients went on to receive
      oral temozolomide at 150-200 mg/m(2) for 5 days every 28 days. RESULTS: Twenty
      three patients were enrolled. Median age was 57 years (range 43-72) and median
      Karnofsky performance status was 90 (range 70-100). Seventeen patients had
      received subtotal resection of the tumor, while six patients had biopsied-only
      tumors. Four patients responded to treatment (17.5%) with additional 14 (61%)
      experiencing stable disease for an overall disease control rate of 78.5%. Median
      progression-free and overall survival were 6.8 and 10.1 months, respectively. The
      concomitant radiotherapy-gemcitabine combination was well tolerated and severe
      adverse events were rare, consisting of grade 3 neutropenia and
      hypertransaminasemia in two cases each. Twenty patients were assessable for
      methylguanine methyltransferase (MGMT) promoter methylation, 11 of which were
      found methylated. In the methylated and unmethylated cohorts, disease control was
      obtained in 10/11 patients (91%) and 7/9 patients (77.5%), respectively.
      CONCLUSIONS: Concomitant radiotherapy-gemcitabine is active and well tolerated in
      newly diagnosed glioblastoma multiforme. Activity is observed both in tumors with
      methylated and unmethylated MGMT promoter.

PMID- 19847427
TI  - Development of antisynthetase syndrome in a patient with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) and antisynthetase syndrome (ASS) are distinct clinical
      syndromes, and their co-occurrence is rarely encountered. The authors report the
      case of a 56-year-old female patient with RA of 3 years duration who suddenly
      developed ASS, and include a review of the literature. The patient was diagnosed
      with ASS based on; positivity for anti-histidyl-tRNA synthetase (Jo-1) antibody,
      interstitial lung disease, polyarthritis, and mechanic's hands. High-dose
      corticosteroid and pulse intravenous cyclophosphamide were used to control the
      ASS. This case demonstrates that ASS should be considered during clinical
      presentations due to its potential overlap with RA.

PMID- 19847428
TI  - Angiotensin converting enzyme DD genotype is associated with development of
      rheumatic heart disease in Egyptian children.
AB  - Angiotensin converting enzyme (ACE) gene polymorphism was previously studied in
      some cardiovascular diseases. There are only few studies which investigated this
      polymorphism in patients with rheumatic heart disease (RHD). The results of these
      investigations are inconsistent. Furthermore, gene polymorphism distribution is
      different in various ethnic populations. We conducted this study to demonstrate
      this gene polymorphism in Egyptian children with RHD. Leukocytes DNA was
      extracted from 139 patients with RHD and 79 healthy control children. After
      amplification by the PCR, the products were separated by electrophoresis in 6%
      polyacrylamide gel and visualized after ethidium bromide staining with UV light.
      The PCR product is a 190-bp fragment in the absence of the insertion (D allele)
      and a 490-bp fragment in the presence of the insertion (I allele). Gene
      polymorphism was as follows: DD gene when lane contains only 190-bp fragment, II
      gene when lane contains only 490-bp fragment and ID gene when lane contains both
      fragments. We found that gene polymorphism in both control and patients groups
      followed the following order of distribution from highest to lowest: ID, II, DD
      gene. The frequency in control group was 49.4, 36.7, and 13.9%, respectively. In
      patients groups, the gene frequency was 42.5, 30.9, and 26.6%, respectively. DD
      gene frequency differs significantly between the two groups. We concluded that
      patients with RHD have a higher ACE-DD genotype than normal control. ACE-DD
      genotype may be a risk factor for RHD in Egyptian children.

PMID- 19847429
TI  - Lupus or tuberculosis: which comes first?

PMID- 19847430
TI  - Synovial tissue rank ligand expression and radiographic progression in rheumatoid
      arthritis: observations from a proof-of-concept randomized clinical trial of
      cytokine blockade.
AB  - The objective of the study was to evaluate synovial tissue receptor activator of
      nuclear factor-kappabeta ligand (RANKL) and osteoprotegerin (OPG) as biomarkers
      of disease activity, progressive joint damage, and therapeutic response, during
      cytokine blockade in rheumatoid arthritis (RA). Patients with active RA entered a
      randomized open-label 12-month study of anakinra 100 mg/day, administered as
      monotherapy or in combination with pegsunercept 800 MUg/kg twice weekly.
      Arthroscopic synovial tissue biopsies were obtained at baseline, at 4 weeks and
      at the final time point. Following immunohistochemical staining, RANKL and OPG
      expression was quantified using digital image analysis. Radiographic damage was
      evaluated using the van der Heijde modification of the Sharp scoring system.
      Twenty-two patients were randomized. Baseline expression of RANKL, but not OPG,
      correlated significantly with baseline CRP levels (r = 0.61, P < 0.01). While a
      significant reduction in OPG expression following treatment was observed in
      clinical responders at the final time point (P < 0.05 vs. baseline), RANKL levels
      did not change, and the RANKL:OPG ratio remained unaltered, even at the highest
      levels of clinical response. When potential predictors of radiographic outcome
      were evaluated, baseline RANKL expression correlated with erosive progression at
      1 year (r = 0.71, P < 0.01). Distinct, though related, pathophysiologic processes
      mediate joint inflammation and destruction in RA. Elevated synovial tissue RANKL
      expression is associated with progressive joint erosion, and may be independent
      of the clinical response to targeted therapy. The potential therapeutic
      importance of modulating RANKL in RA is highlighted, if radiographic arrest is to
      be achieved.

PMID- 19847431
TI  - Mannose binding lectin levels are not related to radiographic damage in
      ankylosing spondylitis.
AB  - In the current study we aimed to investigate the effect of MBL deficiency in
      radiographic damage of the spine in a large group of AS patients. One hundred and
      ninety-one AS patients and 85 healthy controls were studied. Disease activity,
      radiological scores, and demographic features were recorded. MBL levels were
      measured with standard ELISA kits. Results showed that median MBL levels in AS
      and healthy controls were 2,530 (range 0-5,861) ng/ml and 3,415 (0-7,950) ng/ml,
      respectively (p = 0.1). MBL deficiency (<500 ng/ml) was comparable in both groups
      (%21.5 in AS, % 17.6; p = 0.5). Disease activity, clinical picture, and therapies
      were not associated with MBL levels. Both BASRI and mSASSS scores were found
      similar in AS patients with or without MBL deficiency [BASRI: MBL < 500 ng/ml:
      6(2-12), MBL >or= 500 ng/ml: 6(2-12); p = 0.75], [mSASSS: MBL < 500 ng/ml: 3(0
      72), MBL >or= 500 ng/ml: 5(0-72); p = 0.81]. We conclude that MBL deficiency
      prevalence is not increased in AS patients and it is not a cause of a severe
      radiographic damage.

PMID- 19847433
TI  - Coexistent pyoderma gangrenosum and tibialis anterior myositis as presenting
      manifestations of Crohn's disease: case report and review of the literature.
AB  - Crohn's disease (CD) is a well defined inflammatory bowel disease. Patients
      primarily present with abdominal pain and diarrhea, however, extra-intestinal
      manifestations due to musculoskeletal and cutaneous involvement are seen in a
      varying range of patients. In this communication we describe a young woman who
      presented with a severe inflammatory illness that consequently developed into
      pyoderma gangrenosum, anterior tibialis myositis and arthritis that were all
      antecedent to the intestinal involvement. The patient favorably responded to
      infliximab with concomitant azathioprine therapy.

PMID- 19847432
TI  - The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and
      IL-17/IL-6 secretion in rheumatoid arthritis patients.
AB  - Objective of the study is to assess the effects of adalimumab and MTX therapy on
      peripheral Th17 cells and IL-17/IL-6 secretion in RA patients. Twenty active RA
      patients were treated with oral MTX 15 mg per week (MTX group, n = 10), or
      hypodermal adalimumab 40 or 80 mg every other week (ADA group, n = 10).
      Peripheral blood samples were taken for laboratory evaluation at week 0 and week
      12 of treatment, including flowcytometric detection of peripheral CD4(+) IL-17(+)
      cells, RT-PCR detection of mRNA expressions of IL-17, RORc and FoxP3, and ELISA
      determination of serum IL-17 and IL-6. Ten age and sex marched healthy volunteers
      were included as normal controls. Results showed that (1) DAS28 in both groups
      improved at week 12 compared to week 0 (3.9 +/- 1.3 vs. 6.4 +/- 1.4 and 3.2 +/-
      0.9 vs. 5.2 +/- 0.9, respectively). (2) The percentage and MFI of peripheral
      CD4(+) IL-17(+) cells in RA patients were significantly higher comparing to
      normal controls (1.64 +/- 0.97% vs. 0.75 +/- 0.20%, p < 0.01; and 29.8 +/- 9.7
      vs. 19.8 +/- 4.6, p < 0.05, respectively), and positively correlated with ESR and
      DAS28. Peripheral Th17 cells and serum IL-6 in RA patients decreased after
      treatment (from 1.60 +/- 0.78% to 1.28 +/- 0.41%, and from 17.15 +/- 14.53 pg/ml
      to 6.97 +/- 5.51 pg/ml, p < 0.05, respectively). Peripheral FoxP3 mRNA expression
      in active RA patients was significantly lower comparing to normal controls, and
      negatively correlated with ESR. Baseline Th17 percentage of RA patients
      negatively correlated with DAS28 improvement after treatment. In conclusion,
      adalimumab and MTX treatment down regulates peripheral Th17 cells and serum IL-6
      level in RA patients. Baseline Th17 level negatively predicts the effect of
      adalimumb/MTX treatment.

PMID- 19847434
TI  - Multiple symptoms of higher brain dysfunction caused by Marchiafava-Bignami
      disease in a patient with dermatomyositis.
AB  - A 65-year-old woman with dermatomyositis (DM) was admitted because of
      disorientation, mental dysfunction, and disturbance of consciousness. Prior to
      admission, she suffered from septic and hypovolemic shock. There was no evidence
      of active DM on physical examination and laboratory tests. Cerebrospinal fluid
      examination revealed no signs of meningitis. Because of clinical symptoms and
      findings on magnetic resonance images, such as the lesion in the splenium of the
      corpus callosum that was a low-intensity area on T1-weighted images and a high
      intensity on T2-weighted images; she was diagnosed as Marchiafava-Bignami disease
      (MBD). She received a combination of vitamin B, vitamin E, vitamin C, and
      nicotinic acid. Her symptoms improved gradually, and she was discharged at 1.5
      months after admission. There has been no report of a case of DM with MBD. This
      report may provide useful data with regard to the mechanisms of central nervous
      system (CNS) disorders in patients with DM.

PMID- 19847435
TI  - Microscopic polyangitis complicating double carcinoma of the stomach and
      duodenum: improvement after the resection of these carcinomas.
AB  - A 74-year-old woman developed fever, numbness of legs and glomerulonephritis.
      Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase (MPO-ANCA)
      were positive in her serum, and she presented with acute renal failure. She was
      also simultaneously diagnosed as having both gastric and duodenal cancers.
      Complete resection of both cancers and renal biopsy was performed. Some glomeruli
      showed cellular crescentic changes, while submucosal necrotizing vasculitis of
      small vessels was noted adjacent to the gastric cancer. A diagnosis of
      microscopic polyangitis was made. After the operation, the patient's fever, renal
      failure and microscopic hematuria improved and obvious reductions in her serum
      soluble receptors of interleukin 2 values and MPO-ANCA titer were observed
      without any further treatment. However, the patient's proteinuria, cylinduria,
      and elevated C-reactive protein persisted; these findings eventually resolved
      after treatment with 30 mg of prednisolone daily. An immunohistochemical analysis
      showed that CD8 T lymphocytes had infiltrated both the carcinomas and the renal
      lesions. Our case suggests that CD8 T cells induced as part of an immune response
      against carcinoma may play a pathologic role in ANCA-positive paraneoplastic
      syndrome.

PMID- 19847436
TI  - Comparative study on circulating endothelial progenitor cells in systemic lupus
      erythematosus patients at active stage.
AB  - Circulating endothelial progenitor cells (CEPCs) play an important role in the
      process of atherosclerosis. Most previous studies on CEPC in systemic lupus
      erythematosus (SLE) patients were on their number and some functions and the
      results were not consistent. No studies on their anti-inflammatory function and
      integrated status were reported. The purpose of this study was to determine the
      number, function (including anti-inflammatory function), and the integrated
      status of CEPCs in active SLE patients. The study was performed in 35 active SLE
      patients (28 females, 7 males) and 35 age-and gender-matched healthy controls.
      CEPC number was determined by Fluorescence-Activated Cell Sorting. Proliferation
      capacity of CEPC was assessed by PCNA staining. Adhesion capacity of CEPC to
      fibronectin and adhesion capacity of THP1 cell to CEPC were determined by cell
      adhesion assay. Migratory capacity of CEPC was measured by transwell chamber
      assay and the potential to form tubes on Matrigel of CEPC was determined by in
      vivo tube formation on Matrigel test. The expression of inducible nitric oxide
      synthase (iNOS) and interleukin-6 (IL-6) assessed by quantitative PCR as well as
      the expression of intercellular adhesion molecule-1 (ICAM-1) and phosphorylated
      Akt (p-Akt) assessed by western-blotting were used to evaluate the anti
      inflammatory function and cell status of CEPCs. The number of CEPC in SLE
      patients was not different from that in control (p > 0.05). Proliferation
      capacity of CEPC was decreased in active SLE patients (p = 0.027). Adhesion
      capacity of CEPC to fibronectin was decreased (p = 0.04) in SLE patients and
      adhesion capacity of THP1 cell to CEPC was increased in SLE patients (p < 0.001).
      Migratory activity was reduced in patient CEPCs (p < 0.001). Capacity of CEPCs to
      form tube on Matrigel was decreased in SLE patients (p < 0.001). Expression of
      iNOS and IL-6 (p < 0.001, p = 0.006, respectively) and ICAM-1 were increased in
      CEPC of SLE patients and expression of p-Akt was decreased in CEPC of SLE
      patients. Our data show that CEPC number in active SLE patients was not
      significantly different from healthy controls, but their functions were partly
      impaired, including proliferation, adhesion, migration, and tube formation. Bad
      cell status and increased susceptibility to inflammatory process of CEPCs in
      active SLE were also observed in our study.

PMID- 19847437
TI  - Genetic and epigenetic instability of amplification-prone sequences of a novel B
      chromosome induced by tissue culture in Plantago lagopus L.
AB  - Gene amplification is prevalent in many eukaryotes and has been found linked to
      various phenomena such as ontogenesis, carcinogenesis, in vitro culturing,
      neoplasia and drug resistance. Earlier, we reported a novel B chromosome in
      Plantago lagopus L., which was found to have arisen as a result of massive
      amplification of 5S rDNA. In addition, the chromosome is also composed of 45S
      rDNA and transposable elements. While the importance of gene amplification cannot
      be underestimated, its mechanism of origin is still unclear. Therefore, the aim
      of the present study was to determine whether amplification can be reactivated in
      the novel B chromosome. For this purpose, in vitro culture was used as stress.
      Three modes of tissue culture, i.e., direct, indirect and somatic embryogenesis
      were used for raising in vitro cultures. The variations due to genetic and
      epigenetic mechanisms were assessed in regenerants using molecular techniques,
      namely, PCR-RFLP, SSAP and MSAP. The retrotransposon-based molecular markers were
      applied to detect the polymorphism within transposable elements of in vitro
      regenerated and mother plants. We detected the variations that may be due to
      genetic changes either because of element recombination or activation of
      transposable elements which can lead to increase in the copy number. MSAP
      analysis revealed the differences in the DNA methylation pattern of the
      regenerants derived from novel chromosome bearing mother plants. Some regenerated
      plants were associated with increase and decrease in DNA methylation of both
      internal and external cytosine of the CCGG sequence.

PMID- 19847438
TI  - Laparoscopic dismembered pyeloplasty: technique and results in 105 patients.
AB  - PURPOSE: To evaluate the postoperative and functional results of the laparoscopic
      dismembered pyeloplasty (LDP). PATIENTS AND METHODS: Between May 2000 and April
      2008, we performed in our department 105 LDP. All patients presented an
      ureteropelvic junction obstruction with dilatation of renal calyx system with an
      enlarged renal pelvis. Demographic data (age, gender), perioperative and
      postoperative parameters, including operating time, estimated blood loss,
      complications, length of hospital stay, functional outcome were collected and
      evaluated. RESULTS: The mean operative time for LDP was 150 min (range 120-180
      min) and the mean estimated blood loss was negligible in all patients. The mean
      hospital stay was 4 days (4-8). No conversion to open surgery occurred. In the
      follow-up, we noted a successful rate in 96.2% of the patients. CONCLUSION:
      Laparoscopic dismembered pyeloplasty, if performed by expert surgeons in high
      volume centres, presents results that are comparable with open surgery, with a
      lower surgical trauma for the patients.

PMID- 19847439
TI  - Radical cystectomy in the elderly patient: a contemporary comparison of
      perioperative complications in a single institution series.
AB  - PURPOSE: To report on our recent experience with peri- and postoperative
      morbidity of radical cystectomy in patients 75 years and older compared to
      younger patients. PATIENTS AND METHODS: Medical records of 326 consecutive
      patients undergoing radical cystectomy from May 2004 through April 2008 were
      reviewed. RESULTS: Eighty-five of 326 patients (26%) were > or =75 years (75-95)
      old. ASA score was equal 3 or greater in 51% of patients > or =75 years and 32%
      of patients <75 years. Ileal conduit was performed in 83% of patients > or =75,
      16% received an ileal neobladder compared to 46 and 51%, respectively, in
      patients <75. A total of 33 patients (39%) in the older patient group received
      blood transfusions intraoperatively compared to 76 patients (32%) in the younger
      age group. In 6 patients > or =75 years (7.1%) and 17 patients <75 (7.1%) open
      surgical revision was necessary, perioperative complication rate was 22 and 21%,
      respectively. The most common complications were wound dehiscence (5.9 vs. 7.5%),
      infections (4.7 vs. 4.6%), and pulmonary embolism (3.5 vs. 2.1%). Perioperative
      mortality was 1.2% (1 patient) in the elderly versus 0.4% (1 patient) in the
      younger age group. CONCLUSION: Our data show that radical cystectomy can be
      offered to the elderly patient with acceptable morbidity. Because of higher
      comorbidity rate in the elderly, therapeutic decision for radical cystectomy in
      elderly patients should be made carefully and individually. Nevertheless our
      results demonstrate that age itself is not a main criterion which has to be
      considered strongly in decision making for radical cystectomy.

PMID- 19847440
TI  - Physiological, behavioral, and ecological aspects of migration  in reptiles.
AB  - Seasonal movements between foraging, breeding, and overwintering sites occur in a
      wide variety of reptile species. Terrestrial snakes, lizards, and turtles migrate
      short distances (?20 km) between seasonal habitats, whereas fully aquatic marine
      turtles migrate hundreds to thousands of kilometers between foraging and breeding
      areas. The purpose of this article is to summarize aspects of migratory
      physiology and behavior in reptiles, particularly with regards to energetics and
      sensory mechanisms for navigation and orientation. We discuss the influence of
      aerobic scope, endurance, and cost of transport on migratory capacity, the
      effects of temperature and circulating hormones on activity and behavior, and
      mechanisms of detecting and transducing environmental cues to successfully
      navigate and orient toward a goal during migration. Topics worthy of further
      research are highlighted in the text, and we conclude with a discussion of how
      information on migration patterns of reptiles may be used to manage and conserve
      threatened populations.

PMID- 19847441
TI  - Recurrent obstructive hydrocephalus in a 4-month-old infant.
AB  - INTRODUCTION: Transient, recurrent or permanent causes of hydrocephalus in
      children are usually due to tumours, cerebral bleeding or colloid cysts and
      complications of infectious meningitis or secondary to poisoning. Recurrent,
      obstructive hydrocephalus is very rare. CASE REPORT: We report a 4-month-old boy
      who suffered at least three different episodes of obstructive hydrocephalus
      presumably caused by intermittent valvular blockage of the normal aqueduct
      cerebrospinal flow as indirectly demonstrated by serial standard and dynamic
      brain imaging studies. In addition, he had congenital left hydronephrosis
      secondary to congenital ureteropelvic junction stenosis. The child underwent an
      endoscopic third ventriculostomy with only transient post-surgical complications
      (i.e. central diabetes insipidus). DISCUSSION: The neurological symptoms rapidly
      improved after surgery, and the child is currently doing well with normal
      psychomotor development.

PMID- 19847443
TI  - The 22nd International Symposium on Paediatric Surgical Research.

PMID- 19847442
TI  - Oral insulin stimulates intestinal epithelial cell turnover in correlation with
      insulin-receptor expression along the villus-crypt axis in a rat model of short
      bowel syndrome.
AB  - PURPOSE: It has been reported that oral insulin (OI) has a trophic effect on
      intestinal mucosa. In the present study, we evaluated the effect of OI on
      enterocyte turnover and correlated it with insulin-receptor expression along the
      villus-crypt axis in a rat model of short bowel syndrome (SBS). METHODS: Male
      rats were divided into three groups: Sham rats underwent bowel transection, SBS
      rats underwent a 75% bowel resection, and SBS-OI rats underwent bowel resection
      and were treated with OI given in drinking water (1 U/ml) from the fourth
      postoperative day. Parameters of intestinal adaptation, enterocyte proliferation
      and apoptosis were determined on day 15. Real-time PCR was used to determine the
      level of insulin receptor-beta (IRB) mRNA. Insulin-receptor expression along the
      villus-crypt axis (villus tips, lateral villi and crypts) was assessed by
      immunohistochemistry. The effect of OI on cell turnover for each compartment was
      evaluated in correlation with the receptor expression. Statistical analysis was
      performed using the one-way ANOVA test, with P < 0.05 considered statistically
      significant. RESULTS: Treatment with OI resulted in a significant increase in all
      parameters of intestinal adaptation. Insulin-receptor expression in crypts
      significantly increased in SBS rats (vs. Sham rats) and was accompanied by a
      significant increase in enterocyte proliferation following OI administration. A
      significant increase in insulin-receptor expression at the tip of the villous and
      in the lateral villous in SBS rats (vs. Sham) was accompanied by decreased cell
      apoptosis in these compartments following treatment with OI. CONCLUSIONS: In a
      rat model of SBS, OI enhances enterocyte turnover and stimulates intestinal
      adaptation. The stimulating effect of insulin on enterocyte turnover correlates
      with insulin-receptor expression along the villus-crypt axis.

PMID- 19847444
TI  - Carbon dioxide modifies the morphology and function of mesothelial cells and
      facilitates transepithelial neuroblastoma cell migration.
AB  - BACKGROUND: The response of mesothelial cells to surgical trauma and bacterial
      contamination is poorly defined. We have recently shown that CO(2)
      pneumoperitoneum increases systemic metastasis of neuroblastoma cells in a murine
      model. Thus, we hypothesized that CO(2) alters the morphology and function of
      mesothelial cells and facilitates transmesothelial tumor cell migration.
      MATERIALS AND METHODS: Murine mesothelial cells were exposed to 100% CO(2) and 5%
      CO(2) as control. Scanning electron microscopy (SEM) investigations, as well as
      LPS-induced granulocyte-colony stimulating factor (G-CSF) production and
      mitochondrial activity (MTT assay) were measured. Transmesothelial migration of
      neuroblastoma cells (Neuro2a) was determined using a transwell chamber system.
      RESULTS: CO(2) incubation was associated with a significant destruction of the
      microvillar formation in SEM. Migration studies showed that the barrier function
      of the mesothelial monolayer decreased. A significantly increased migration of
      neuroblastoma cells was identified after 100% CO(2) exposure (P < 0.05). Although
      the conversion of MTT as an indicator of mitochondrial activity was only slightly
      and not significantly reduced after CO(2) incubation, the release of G-CSF
      induced by LPS was completely blocked during the incubation with 100% CO(2) (P <
      0.05). The capacity of G-CSF release recovered after the incubation. CONCLUSION:
      We observed that peritoneal mesothelial cells lose their typical cell morphology
      by CO(2) incubation, which is accompanied by facilitated migration of
      neuroblastoma cells. Moreover, the synthesis of immunological factors is blocked,
      but this effect is not long lasting. These mechanisms may explain an increased
      metastasis rate of neuroblastoma cells after CO(2) pneumoperitoneum, which was
      recently observed in a murine model.

PMID- 19847445
TI  - Microsatellite instability screening should be done for right-sided colon cancer
      patients less than 60 years of age.
AB  - BACKGROUND AND AIMS: Microsatellite analysis is a screening tool used for the
      identification of Lynch syndrome. We evaluated the occurrence of high-frequency
      microsatellite instability (MSI-H) in 160 patients with colorectal cancer < or
      =60 years old to determine if these individuals should be routinely tested for
      microsatellite instability. MATERIALS AND METHODS: From January 2004 and December
      2006, we tested specimens of colorectal cancer from 160 patients under 60 years
      of age for microsatellite instability. The relationships between
      clinicopathological parameters and MSI-H status were analyzed. RESULTS: MSI-H
      occurred in 11.3% (18/160) of the tumors assayed, and colorectal tumors with MSI
      H status were located predominantly to the right side (56%, P < 0.001) and had a
      lower pathological stage (72%, P = 0.011). Of the 18 MSI-H tumors, six displayed
      characteristic MSI histology. Furthermore, of the 18 MSI-H tumors, instability in
      BAT-26 was 100%, BAT-25 was 94%, D17S250 was 72%, D2S123 was 68%, and D5S346 was
      68%. Of the patients with MSI-H tumors, 55.6% were more than 50 years of age, and
      about 70% of MSI-H tumors did not display characteristic MSI histology.
      Importantly, up to 40% of the MSI-H patients in this study would have been
      overlooked using the revised Bethesda guidelines. The revised Bethesda
      guidelines, broadened to include patients with right-sided colon cancer, could
      have identified 94% of the MSI-H tumors in this study. CONCLUSIONS: Colorectal
      cancers with MSI-H were predominantly located on the right side and had an early
      pathological stage. The results of this study suggest that microsatellite
      instability test should be used for all patients under 60 years of age with right
      sided colon cancer.

PMID- 19847446
TI  - [Effector function plasticity of T helper lymphocytes].
AB  - T helper (Th) cells are grouped into functionally different subsets (considered
      hitherto distinct and stable) according to their cytokine production. However, a
      number of recent findings show a much higher degree of Th cell plasticity and
      interconvertibility than previously assumed. Therefore, Th effector functions
      might be subject to therapeutic modulation even in late stages of
      immunopathological diseases.

PMID- 19847448
TI  - GFAP, Ki67 and IDH1: perhaps the golden triad of glioma immunohistochemistry.

PMID- 19847449
TI  - Bilateral humerus fracture in a neonate after cesarean delivery.
AB  - Humerus fractures in neonates are rare, but can occur during cesarean section and
      bilateral humerus fracture has not been reported yet. This case represents a
      newborn delivered by cesarean section for breech presentation which resulted in
      bilateral humerus fracture.

PMID- 19847450
TI  - Derivations that enable the testing of fetal urine production as a method of
      fetal surveillance.
AB  - PURPOSE: To calculate the measurement error of the hourly fetal urine production
      rate (HFUPR) and evaluate the implication of different methods for measuring the
      HFUPR, i.e. ellipsoid versus sum-of-cylinders method. METHODS: The calculation
      was based on sonographic documentation of the increased bladder volumes during
      the filling phase, the bladder volume measurement error and the number and time
      points of bladder image capture. RESULTS: The probability of a false pathological
      reading was excluded (0%) with the sum-of-cylinders method for gestational ages
      of >=30 weeks. With the ellipsoid method, the risk was higher. The maximum
      changes which could be exclusively explained by measurement error were four to
      five times greater with the ellipsoid method compared with the sum-of-cylinders
      method. CONCLUSIONS: The present paper illustrates a careful evaluation of the
      HFUPR measurement error and the implications of using different ultrasound
      methods for bladder volume estimations.

PMID- 19847451
TI  - Specific secretory phase endometrial leukocytes of women with two and more
      consecutive idiopathic abortions are not significantly different from healthy
      controls.
AB  - OBJECTIVE: To analyze concentrations of endometrial leukocytes in patients with
      idiopathic-repeated abortions. MATERIALS AND METHODS: Biopsies of exactly dated
      secretory endometrium in 25 patients with idiopathic-repeated abortions and 10
      control patients without a history of miscarriage were compared with respect to
      the concentrations of T-helper cells (CD4), cytotoxic T-cells (CD8), B-cells
      (CD19) and uterine natural killer cells (CD56) by immunohistochemistry and RNase
      protection assays. RESULTS: All examined cells were detectable within secretory
      endometrium. No statistically significant differences of the examined immune-cell
      concentrations were seen between the control group and the repeated miscarriage
      group by either test. CONCLUSION: This study suggests that the concentrations of
      specific endometrial leukocytes in a non-pregnant cycle are not associated with
      repeated pregnancy loss. Thus, the hypothesis of an altered endometrial immunity
      in patients with repeated miscarriages, symbolized by persistently differing
      local immune-cell concentrations, has to be questioned.

PMID- 19847447
TI  - Oligodendrocytes: biology and pathology.
AB  - Oligodendrocytes are the myelinating cells of the central nervous system (CNS).
      They are the end product of a cell lineage which has to undergo a complex and
      precisely timed program of proliferation, migration, differentiation, and
      myelination to finally produce the insulating sheath of axons. Due to this
      complex differentiation program, and due to their unique metabolism/physiology,
      oligodendrocytes count among the most vulnerable cells of the CNS. In this
      review, we first describe the different steps eventually culminating in the
      formation of mature oligodendrocytes and myelin sheaths, as they were revealed by
      studies in rodents. We will then show differences and similarities of human
      oligodendrocyte development. Finally, we will lay out the different pathways
      leading to oligodendrocyte and myelin loss in human CNS diseases, and we will
      reveal the different principles leading to the restoration of myelin sheaths or
      to a failure to do so.

PMID- 19847452
TI  - Evaluation of pelvic posterior exenteration in the management of advanced-stage
      ovarian cancer.
AB  - PURPOSE: The main aim of this study was to show the interest of pelvic posterior
      exenteration to obtain complete resection of the tumor in case of invasion of the
      rectum by contiguity in advanced-stage ovarian cancer. The secondary aim was to
      determine the morbidity of this surgery. METHODS: It is a multicentric,
      retrospective study of a series of 41 patients, who underwent posterior
      pelvectomy for advanced-stage ovarian cancer, over a period of 18 years, from
      July 1989 to July 2007. RESULTS: The surgery resulted in macroscopically complete
      resection in 19 patients (46.34%), a residual tumor <2 cm in 19 patients (46.34%)
      and >2 cm in 3 patients (7.32%). In 34 patients (34/41), digestive continuity
      with satisfactory anal sphincter function was restored immediately or in the
      short term. The mean delay to the start of complementary treatment was 36 days.
      Median overall survival was 33 months. CONCLUSION: The main aim of surgery for
      ovarian peritoneal carcinomatosis is to obtain a complete resection. In the case
      of direct invasion of the rectum by contiguity, when there is no cleavage plane
      between the uterus and the rectum, pelvic posterior exenteration is an effective
      method to achieve this objective. Morbidity is relatively high, but acceptable
      given the poor prognosis of this disease, the improved survival after surgery,
      and improvements in post-operative quality of life and functions.

PMID- 19847453
TI  - Delayed-interval delivery of an in vitro-fertilized triplet pregnancy with
      premature rupture of membranes in the second trimester.
AB  - BACKGROUND: The incidence of multiple pregnancies is increasing with the
      availability of assisted reproductive techniques. Preterm labor and preterm
      rupture of membranes are major complications in such pregnancies. Preterm
      delivery of the first fetus is often followed by delivery of the remaining
      fetuses. However, conservative management in such circumstances might allow for
      fetal lung maturity in the remaining fetuses. CASE: We present a case of
      conservative management of an in vitro-fertilized triplet pregnancy with early
      loss of the leading triplet. A 33-year-old woman in the 21st week of a triplet
      pregnancy delivered her one of the fetuses, 4 days after the preterm rupture of
      membranes. To save the surviving fetuses, ligation of the umbilical cord at the
      cervical level was performed. Patient received antibiotics, tocolytics and
      corticosteroids after then. The second and the third fetuses were successfully
      delivered by cesarean section in the 28th week of pregnancy, 43 days after the
      first fetus was born. CONCLUSION: We can improve the life expectancy of the
      retained fetuses by conservative management using tocolytics, antenatal steroids
      to stimulate lung maturation and antibiotics following the delivery of the first
      fetus.

PMID- 19847454
TI  - A reappraisal of three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR), and five
      marker (ER/Vim/CEA/PR/p16INK4a) panels in the diagnostic distinction between
      primary endocervical and endometrial adenocarcinomas in a tissue microarray
      study.
AB  - BACKGROUND: The choice of appropriate therapeutic plans for primary endocervical
      adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) depend on the tumor's
      site of origin. The purpose of this study was to compare the performances of the
      commonly used three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR) and five
      marker (ER/Vim/CEA/PR/p16INK4a) panels in distinguishing between primary ECA and
      EMA. METHODS: A tissue microarray was constructed using paraffin-embedded,
      formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21
      EMA. Utilizing the avidin-biotin (ABC) technique, tissue array sections were
      immunostained with five commercially available antibodies (ER, Vim, CEA, PR and
      p16INK4a) to evaluate the performances of their respective three-, four- and five
      marker panels in distinguishing between primary ECA and EMA. RESULTS: ER, PR and
      Vim were more likely to be expressed in EMA, while CEA and p16INK4a were
      frequently expressed in ECA. The three-marker (ER/Vim/CEA) panel exhibits the
      most favorable performance in the distinction between these two gynecologic
      malignancies (ECA vs. EMA). CONCLUSION: According to our data, when
      histomorphological and clinical doubt exists as to the primary site of origin, we
      recommend that the conventional three-marker (ER/Vim/CEA) panel is sufficient,
      appropriate and useful in distinguishing between primary ECA and EMA, instead of
      the four-marker (ER/Vim/CEA/PR) and five-marker (ER/Vim/CEA/PR/p16INK4a) panels.
      Ancillary PR and p16INK4a add no supplementary value to the performance of the
      conventional three-marker (ER/Vim/CEA) panel.

PMID- 19847455
TI  - Effects of extracochlear gacyclidine perfusion on tinnitus in humans: a case
      series.
AB  - Gacyclidine, a non-competitive NMDA receptor antagonist, is a phencyclidine
      derivative with neuroprotective properties. It has been previously safely
      administered intravenously to acute traumatic brain-injured patients. Experiments
      in guinea pigs have shown that local administration of gacyclidine to the cochlea
      can suppress salicylate-induced tinnitus. Thus, we thought that patients with
      therapy-resistant sensorineural tinnitus might benefit from a local therapy with
      gacyclidine. As a compassionate treatment, we administered aqueous gacyclidine
      solution via a Durect RWmuCath(TM) into the round window niche in six patients
      with unilateral deafness associated with tinnitus. The response of each patient
      to the drug treatment was given a numerical value by the use of a visual analogue
      scale (VAS) on a scale of 0-10 for tinnitus intensity, where 0 represented no
      tinnitus and 10 represented unbearable tinnitus-intensity or -annoyance
      (subjective). After constant perfusion of gacyclidine for 40-63 h, four out of
      six patients experienced a temporary relief from their tinnitus. No serious side
      effects were recorded in any of the cases. Gacyclidine might present a potent
      drug for the suppression of sensorineural tinnitus in humans and therefore should
      be considered for future double-blinded, placebo-controlled clinical trials. For
      lasting effective treatment, controlled intracochlear and long-term delivery of
      the drug seems to be necessary. Further studies investigating the toxicological
      effects of gacyclidine intracochlear perfusion as well as different dosages and
      therapy durations are under way to ensure the safety of the drug for long-term
      human use and warrant clinical trials.

PMID- 19847457
TI  - Central corneal thickness and retinal vein occlusions: the Beijing Eye Study.

PMID- 19847458
TI  - Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells.
AB  - Controlled invasion of the uterine wall by the trophoblast cells is pivotal for
      the successful pregnancy, and various kinds of protease are involved in this
      process. Serine protease prostasin has been shown to participate in the
      proteolytic activation of epithelial sodium channel as well as cleavage of
      epidermal growth factor receptor extracellular domain in human epithelial cells.
      Its physiological significance in human placentation has been suggested but not
      validated. In the present study, we found that prostasin was expressed at a
      relatively high level in human placenta trophoblasts in early pregnant weeks. In
      the in vitro cultured human choriocarcinomal JEG-3 cells, treatment with
      functional antibody against prostasin led to promotion in cell invasion
      capability, as well as increase in the production of MMP-2, MMP-26, TIMP-1, and
      TIMP-4. Our data indicated that this serine protease may function as an invasion
      suppressor in human trophoblast, participating in the invasion-restrictive
      regulation of trophoblasts to avoid their over-penetration into the uterine wall.

PMID- 19847459
TI  - PCR-based subtyping of Blastocystis isolates from symptomatic and asymptomatic
      individuals in a major hospital in Ankara, Turkey.
AB  - The stool samples obtained from 94 patients with gastrointestinal symptoms and
      109 asymptomatic individuals, who checked in due to other reasons, admitted at a
      major hospital in Ankara, Turkey were examined with native Lugol's iodine,
      trichrome, and Kinyoun's acid-fast stainings for parasitology examinations and
      with in vitro culture method for detection of Blastocystis. In a total of 203
      stool samples tested, native Lugol's iodine and trichrome stainings could detect
      12 (5.9%) and 20 (9.9%) positive samples for Blastocystis, respectively.
      Conversely, culture method could detect 66 (32.5%) positive samples, and this
      method was more sensitive compared to the both microscopic examinations (p <
      0.001). Among 66 positive samples for Blastocystis, 27 were from symptomatic
      patients and 39 were from asymptomatic group. Subtypes (STs) were determined by
      PCR using seven different sequence-tagged site primers. ST3 was the most dominant
      in both symptomatic and asymptomatic groups and followed by ST1 or ST2. There
      were mixed infections with STs 1 and 2 or STs 1 and 3 in nine isolates. There was
      no statistical significance of the distribution of Blastocystis sp. subtypes
      between symptomatic and asymptomatic individuals (p > 0.05).

PMID- 19847461
TI  - Design of a new rotating drum bioreactor operated at atmospheric pressure on the
      bioremediation of a polluted soil.
AB  - This paper reports the effect of the operation and design characteristics of
      rotating drum bioreactors (RDBs) aerated by natural convection and applied to the
      treatment of a soil highly polluted with weathered total petroleum hydrocarbons
      (TPH) (55,000 +/- 2,600 mg/kg). The parameters studied were length to diameter
      ratio (L/D), rotating speed (N) and lifter type. The highest TPH removal (59.6 +/
      0.7%) was obtained with the RDB of the lowest L/D ratio (1.5). Removals
      diminished by 27, 36 and 56%, with a ratio increment of 2.1, 3.1 and 5.1,
      respectively. Increment of the N, at an optimal value and lifter change from
      straight to helicoidal showed an improvement on the TPH removal of 20 and 30%,
      respectively. According to these results, slurry surface renewal through the
      variation of the N and the change of slurry flow was able to improve TPH removal
      in RDBs operated by natural convection.

PMID- 19847460
TI  - Genetic variants in the RELN gene are associated with otosclerosis in multiple
      European populations.
AB  - Otosclerosis is a common form of hearing loss characterized by abnormal bone
      remodeling in the otic capsule. It is considered a complex disease caused by both
      genetic and environmental factors. In a previous study, we identified a region on
      chr7q22.1 located in the RELN gene that is associated with otosclerosis in
      Belgian-Dutch and French populations. Evidence for allelic heterogeneity was
      found in this chromosomal region in the form of two independent signals. To
      confirm this finding, we have completed a replication study that includes four
      additional populations from Europe (1,141 total samples). Several SNPs in this
      region replicated in these populations separately. While the power to detect
      significant association in each population is small, when all four populations
      are combined, six of seven SNPs replicate and show an effect in the same
      direction as in the previous populations. We also confirmed the presence of
      allelic heterogeneity in this region. These data further implicate RELN in the
      pathogenesis of otosclerosis. Functional research is warranted to determine the
      pathways through which RELN acts in the pathogenesis of otosclerosis.

PMID- 19847462
TI  - Inter- and intrapatients comparison of WHO grade II glioma kinetics before and
      after surgical resection.
AB  - Grade II gliomas grow slowly and linearly (at rates about 4 mm/year) before
      undergoing anaplastic transformation. In order to analyze how surgery may affect
      radiological grade II glioma kinetics, we restrospectively reviewed our national
      database searching for patients operated on for a supratentorial grade II glioma
      between 1997 and 2007. We selected patients with at least two postoperative MRI
      with a minimal delay of 6 months. For each patient, postoperative residues were
      segmented on successive MRIs. Velocities of diameter expansion were estimated by
      linear regression of mean diameter evolution for each patient. Fifty-four
      patients fulfilled inclusion criteria. Median postoperative follow-up was 1.6
      years with, on average, 3.4 MRI examinations per patient. Postoperative growth
      rates of mean diameter were normally distributed, around a mean value of 4.3
      mm/year (SD = 3.2 mm/year). Statistical analysis showed no difference between
      this distribution and the distribution of preoperative growth rates in a previous
      series of 143 grade II gliomas. For a subset of 23 patients, delay between first
      MRI and surgery made it possible to estimate also preoperative growth rates.
      Intrapatient comparison revealed that growth rates were grossly unchanged for 80%
      of cases. In summary, inter- and intrapatient comparison of pre- and
      postoperative growth rates proves that surgery does not change grade II glioma
      dynamics, thus, acting as a cytoreduction.

PMID- 19847464
TI  - Soft Dynamics simulation. 2. Elastic spheres undergoing a T(1) process in a
      viscous fluid.
AB  - Robust empirical constitutive laws for granular materials in air or in a viscous
      fluid have been expressed in terms of timescales based on the dynamics of a
      single particle. However, some behaviours such as viscosity bifurcation or shear
      localization, observed also in foams, emulsions, and block copolymer cubic
      phases, seem to involve other micro-timescales which may be related to the
      dynamics of local particle reorganizations. In the present work, we consider a
      T(1) process as an example of a rearrangement. Using the Soft Dynamics simulation
      method introduced in the first paper of this series, we describe theoretically
      and numerically the motion of four elastic spheres in a viscous fluid.
      Hydrodynamic interactions are described at the level of lubrication (Poiseuille
      squeezing and Couette shear flow) and the elastic deflection of the particle
      surface is modeled as Hertzian. The duration of the simulated T(1) process can
      vary substantially as a consequence of minute changes in the initial separations,
      consistently with predictions. For the first time, a collective behaviour is thus
      found to depend on a parameter other than the typical volume fraction of
      particles.

PMID- 19847463
TI  - Allosteric modulation by benzodiazepines of GABA-gated chloride channels of an
      identified insect motor neurone.
AB  - The actions of benzodiazepines were studied on the responses to GABA of the fast
      coxal depressor (D(f)) motor neurone of the cockroach, Periplaneta americana. Ro5
      4864, diazepam and clonazepam were investigated. Responses to GABA receptors were
      enhanced by both Ro5-4864 and diazepam, whereas clonazepam, a potent-positive
      allosteric modulator of human GABA(A) receptors, was ineffective on the native
      insect GABA receptors of the D(f) motor neurone. Thus, clear pharmacological
      differences exist between insect and mammalian native GABA-gated chloride
      channels with respect to the actions of benzodiazepines. The results enhance our
      understanding of invertebrate GABA-gated chloride channels which have recently
      proved important in (a) comparative studies aimed at identifying human allosteric
      drug-binding sites and (b) understanding the actions of compounds used to control
      ectoparasites and insect crop pests.

PMID- 19847465
TI  - Overstretching of a 30 bp DNA duplex studied with steered molecular dynamics
      simulation: effects of structural defects on structure and force-extension
      relation.
AB  - Single-molecule experiments on polymeric DNA show that the molecule can be
      overstretched at nearly constant force by about 70% beyond its relaxed contour
      length. In this publication we use steered molecular dynamics (MD) simulation to
      study the effect of structural defects on force-extension curves and structures
      at high elongation in a 30 base pair duplex pulled by its torsionally
      unconstrained 5' -5' ends. The defect-free duplex shows a plateau in the force
      extension curve at 120 pN in which large segments with inclined and paired bases
      ("S-DNA") near both ends of the duplex coexist with a central B-type segment
      separated from the former by small denaturation bubbles. In the presence of a
      base mismatch or a nick, force-extension curves are very similar to the ones of
      the defect-free duplex. For the duplex with a base mismatch, S-type segments with
      highly inclined base pairs are not observed; rather, the overstretched duplex
      consists of B-type segments separated by denaturation bubbles. The nicked duplex
      evolves, via a two-step transition, into a two-domain structure characterized by
      a large S-type segment coexisting with several short S-type segments which are
      separated by short denaturation bubbles. Our results suggest that in the presence
      of nicks the force-extension curve of highly elongated duplex DNA might reflect
      locally highly inhomogeneous stretching.

PMID- 19847466
TI  - Differential expression of lipid metabolism related genes in porcine muscle
      tissue leading to different intramuscular fat deposition.
AB  - Intramuscular fat (IMF) content affects meat quality and varies in different pig
      breeds. However, the underlying mechanisms of different IMF depositions in
      different genetic backgrounds of pigs have not been fully elucidated as yet.
      Lipid metabolism theoretically contributes to the variation of IMF content. The
      expression levels of genes and proteins as well as enzyme activities implicated
      in muscle lipid metabolism were investigated, which included lipogenetic genes
      (SREBP-1c and FAS), fatty acid transporting genes (H-FABP and A-FABP), fatty acid
      oxidative gene (CPT-1B) and lipolytic genes (ATGL and HSL) as well as the
      desaturated fatty acid gene (SCD). Longissimus muscle samples were collected from
      fatty Wujin pigs and lean Landrace pigs. Results showed that the average daily
      gain of Wujin pigs was lower than that of Landrace pigs. Wujin pigs had greater
      adipocyte diameter, IMF content and PUFA percentage than that of Landrace pigs.
      Compared with Landrace pigs, Wujin pigs exhibited higher expression levels, both
      in mRNA and protein, of FAS, SREBP-1c, SCD, A-FABP and H-FABP genes and lower
      expression levels of CPT-1B, HSL and ATGL genes. Overall, Wujin pigs possessed
      higher mRNA abundance, protein expression or enzyme activities of anabolism,
      fatty acid transportation and desaturation, and lower catabolism. Therefore, the
      mechanism of higher IMF content in fatty pigs may be due to the higher capacity
      of lipogenesis and fatty acid transportation and the lower capacity of lipolysis.

PMID- 19847467
TI  - Acetaldehyde as an underestimated risk factor for cancer development: role of
      genetics in ethanol metabolism.
AB  - Chronic ethanol consumption is a strong risk factor for the development of
      certain types of cancer including those of the upper aerodigestive tract, the
      liver, the large intestine and the female breast. Multiple mechanisms are
      involved in alcohol-mediated carcinogenesis. Among those the action of
      acetaldehyde (AA), the first metabolite of ethanol oxidation is of particular
      interest. AA is toxic, mutagenic and carcinogenic in animal experiments. AA binds
      to DNA and forms carcinogenic adducts. Direct evidence of the role of AA in
      alcohol-associated carcinogenesis derived from genetic linkage studies in
      alcoholics. Polymorphisms or mutations of genes coding for AA generation or
      detoxifying enzymes resulting in elevated AA concentrations are associated with
      increased cancer risk. Approximately 40% of Japanese, Koreans or Chinese carry
      the AA dehydrogenase 2*2 (ALDH2*2) allele in its heterozygous form. This allele
      codes for an ALDH2 enzyme with little activity leading to high AA concentrations
      after the consumption of even small amounts of alcohol. When individuals with
      this allele consume ethanol chronically, a significant increased risk for upper
      alimentary tract and colorectal cancer is noted. In Caucasians, alcohol
      dehydrogenase 1C*1 (ADH1C*1) allele encodes for an ADH isoenzyme which produces
      2.5 times more AA than the corresponding allele ADH1C*2. In studies with moderate
      to high alcohol intake, ADH1C*1 allele frequency and rate of homozygosity was
      found to be significantly associated with an increased risk for cancer of the
      upper aerodigestive tract, the liver, the colon and the female breast. These
      studies underline the important role of acetaldehyde in ethanol-mediated
      carcinogenesis.

PMID- 19847468
TI  - Serum levels of brain-derived neurotrophic factor correlate with motor impairment
      in Parkinson's disease.
AB  - The brain-derived neurotrophic factor (BDNF) is a potent inhibitor of apoptosis
      mediated cell death and neurotoxin-induced degeneration of dopaminergic neurons.
      There is a growing body of evidence implicating BDNF in the pathogenesis of
      Parkinson's disease (PD), suggesting it may eventually be used in the development
      of neuroprotective therapies for PD. The serum BDNF of 47 PD patients and of 23
      control subjects was assessed, and serum BNDF levels were significantly decreased
      in PD patients when compared with controls (p = 0.046). Interestingly enough,
      BDNF correlated positively with a longer time span of the disease, as well as
      with the severity of the PD symptoms and with more advanced stages of the
      disease. Additionally, higher BDNF levels also correlated with poor balance as
      assessed by the Berg Balance Scale, more time spent at the Timed Up & Go Test,
      reduced speed of gait and shorter distance walked during the Six-Minute Walk
      Test. Our results corroborate the literature regarding the involvement of BDNF in
      PD. We hypothesize that lower BDNF levels in early stages of the disease may be
      associated with pathogenic mechanisms of PD. The increase of BDNF levels with the
      progression of the disease may be a compensatory mechanism in more advanced
      stages of PD.

PMID- 19847469
TI  - An exploration of ocular fixation in Parkinson's disease, multiple system atrophy
      and progressive supranuclear palsy.
AB  - Since the basal ganglia are thought to have a role in controlling ocular fixation
      it is expected that patients with parkinsonian conditions would show impaired
      performance in fixation tasks. Our study examines ocular fixation in patients
      with a range of parkinsonian conditions (Idiopathic Parkinson's Disease, Multiple
      System Atrophy and Progressive Supranuclear Palsy). Eye movements were recorded
      from 44 patients and 50 age matched control subjects during ocular fixation both
      with and without a visible target. The data for each patient were then
      characterised in terms of fixation periods and saccadic intrusions (SI). Patient
      groups exhibited larger and more frequent SI as well as greater displacement from
      the fixation target. Patients with Progressive Supranuclear Palsy exhibit larger
      SI than control subjects when fixation targets are visible, this difference is
      reversed in the absence of a fixation target. Patients with Multiple System
      Atrophy show increased frequency of SI both with and without a visible target.
      Our findings show that ocular fixation is impaired in patients with parkinsonian
      conditions and may prove useful as part of an oculomotor profile to aid with the
      differentiation of parkinsonian conditions.

PMID- 19847471
TI  - Research on the origin of life. Introduction.

PMID- 19847470
TI  - Effects of tryptophan and 5-hydroxytryptophan on the hepatic cell membrane
      rigidity due to oxidative stress.
AB  - The ability of several indoleamines to scavenge free radicals is well documented.
      Our aim was to evaluate the ability of 0.01-3 mM tryptophan (Trp) and 0.1-5 mM 5
      hydroxytryptophan (5-OH-Trp) to protect hepatic cell membranes against 0.1 mM
      FeCl(3) plus 0.1 mM ascorbic acid-induced lipid peroxidation and increases in
      membrane rigidity. Membrane fluidity was evaluated using fluorescence
      spectroscopy. Lipid and protein oxidation were estimated by quantifying
      malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) concentrations and carbonyl
      group content, respectively. Exposure to FeCl(3) plus ascorbic acid increased
      hepatic cell membrane rigidity, MDA + 4-HDA and carbonyl content. The presence of
      5-OH-Trp, but not Trp, attenuated these changes. In the absence of oxidative
      stress, neither indoleamine modified fluidity, MDA + 4-HDA or carbonylation.
      These results suggest that C5 hydroxylation determines the ability of Trp to
      preserve membrane fluidity in the presence of oxidative stress.

PMID- 19847473
TI  - Reconstruction of an isolated left subclavian artery in a patient with a right
      aortic arch and tetralogy of Fallot.
AB  - An isolated left subclavian artery (ILSA) is very rarely seen in patients with a
      right aortic arch. This report describes the case of a 2-year-old boy who
      underwent ILSA reconstruction during repair of the associated tetralogy of Fallot
      to prevent future subclavian steal syndrome after surgery.

PMID- 19847472
TI  - Effect of parathion-methyl on Amazonian fish and freshwater invertebrates: a
      comparison of sensitivity with temperate data.
AB  - Parathion-methyl is an organophosphorous insecticide that is widely used in
      agricultural production sites in the Amazon. The use of this pesticide might pose
      a potential risk for the biodiversity and abundance of fish and invertebrate
      species inhabiting aquatic ecosystems adjacent to the agricultural fields. Due to
      a lack of toxicity data for Amazonian species, safe environmental concentrations
      used to predict the ecological risks of parathion-methyl in the Amazon are based
      on tests performed with temperate species, although it is unknown whether the
      sensitivity of temperate species is representative for those of Amazonian endemic
      species. To address this issue, the acute toxic effect (LC(50)-96 h) of parathion
      methyl was assessed on seven fish and five freshwater invertebrate species
      endemic to the Amazon. These data were used to compare their pesticide
      sensitivity with toxicity data for temperate species collected from the
      literature. The interspecies sensitivity was compared using the Species
      Sensitivity Distribution (SSD) concept. The results of this study suggest that
      Amazonian species are no more, or less, sensitive to parathion-methyl than their
      temperate counterparts, with LC(50) values ranging from 2900 to 7270 microg/L for
      fish and from 0.3 to 319 microg/L for freshwater arthropods. Consequently, this
      evaluation supports the initial use of toxicity data of temperate fish and
      freshwater invertebrate species for assessing the effects of parathion-methyl on
      Amazonian freshwater ecosystems.

PMID- 19847474
TI  - Late rupture of the aorta after interventional treatment of a recoarctation.

PMID- 19847475
TI  - Are biological effects of desert shrubs more important than physical effects on
      soil microorganisms?
AB  - Vegetation cover plays a major role in providing organic matter and in acting as
      a physical barrier, with both together contributing to the formation of "fertile
      islands," which play an active role in prolonging biological activity in desert
      ecosystems. By undertaking this study, a longterm research, we designed an
      experiment to separate the two components-the physical and biotic parts of the
      perennial plants-and to identify the factor that contributes the most to the
      ecosystem. The study site was located in the northern Negev Desert, Israel, where
      50 Hammada scoparia shrubs and 50 artificial plants were randomly marked. Soil
      samples were collected monthly over 3 years of research at three locations: under
      the canopy of H. scoparia shrubs, in the vicinity of the artificial plants, and
      between the shrubs (control). The contribution to microbial activity was measured
      by evaluation of the microbial community functions in soil. The functional
      aspects of the microbial community that were measured were CO2 evolution,
      microbial biomass, microbial functional diversity, and the physiological profile
      of the community. The results of this study are presented in two ways: (1)
      according to the three locations/treatments; and (2) according to the
      phenological situation of the vegetation (annual and perennial plants) in the
      research field: the growing phase, the drying process, and the absence of annual
      plants. The only parameters that were found to affect microbial activity were the
      contribution of the organic matter of perennial shrubs and the growth of
      vegetation (annual and perennial) during the growing seasons. The physical
      component was found to have no effect on soil microbial functional diversity,
      which elucidates the important contribution of the desert shrub in enhancing
      biological multiplicity and activity.

PMID- 19847477
TI  - Experience of 1000 cases on subfascial breast augmentation.
AB  - BACKGROUND: Throughout the years the female breast has been manipulated through
      aesthetic and reconstructive surgery. Since the 18th century there have been
      reports of techniques that have tried to increase the volume of the mammary
      gland. This article demonstrates a technique for increasing the volume of the
      mammary gland by dissection of the fascia of the pectoralis major muscle. This
      technique provides long-term results due to the optimized dynamics between the
      soft tissue and the implant. The subfascial technique is paramount to the
      subglandular method because primarily it offers better palpable firmness in the
      periareolar area, a significant decrease in the step effect produced by an
      excessive projection of the breast, a favorable gravitational pull of the breast,
      and a considerable reduction in the incidence of capsular contractures. The
      movement of the implant, postsurgical pain, and bleeding caused by the incision
      of the pectoralis muscle diminish with this technique. Because of the fascia's
      tendency to be preserved, this procedure has the advantage of being able to be
      applied where previous surgery has been performed; this concedes the subfascial
      technique a more versatile angle. METHODS: In the last 10 years 1000 patients
      were subjected to subfascial breast augmentation with soft-gel cohesive textured
      implants. An inframammary incision was used in 95% of the patients and the
      periareolar incision in 5%. RESULTS: The patient does not suffer from immediate
      postsurgical pain. Recovery time and the ability to start daily activities is
      briefer than after the submuscular procedure. A better projection is obtained
      without the need to use a bigger implant to get the same result because there is
      no pressure on top of the implant as in the submuscular technique. CONCLUSION:
      The subfascial procedure offers a high-grade result for the short and long term
      and has fewer disadvantages than the submuscular or subglandular technique.
      Likewise, there are fewer immediate postoperative symptoms and patients have a
      much better and less painful recovery. The morbidity in these patients is less
      than with the subglandular and submuscular methods.

PMID- 19847476
TI  - Microbial community structure, pigment composition, and nitrogen source of red
      snow in Antarctica.
AB  - "Red snow" refers to red-colored snow, caused by bloom of cold-adapted
      phototrophs, so-called snow algae. The red snow found in Langhovde, Antarctica,
      was investigated from several viewpoints. Various sizes of rounded red cells were
      observed in the red snow samples under microscopy. Pigment analysis demonstrated
      accumulation of astaxanthin in the red snow. Community structure of
      microorganisms was analyzed by culture-independent methods. In the analyses of
      small subunit rRNA genes, several species of green algae, fungus, and various
      phylotypes of bacteria were detected. The detected bacteria were closely related
      to psychrophilic or psychrotolerant heterotrophic strains, or sequences detected
      from low-temperature environments. As predominant lineage of bacteria, members of
      the genus Hymenobacter were consistently detected from samples obtained in two
      different years. Nitrogen isotopic compositions analysis indicated that the red
      snow was significantly 15N-enriched. Based on an estimation of trophic level, it
      was suggested that primary nitrogen sources of the red snow were supplied from
      fecal pellet of seabirds including a marine top predator of Antarctica.

PMID- 19847478
TI  - Evaluating participatory modeling: developing a framework for cross-case
      analysis.
AB  - Participatory modeling is increasingly recognized as an effective way to assist
      collective decision-making processes in the domain of natural resource
      management. This article introduces a framework for evaluating projects that have
      adopted a participatory modeling approach. This evaluation framework--known as
      the "Protocol of Canberra"--was developed through a collaboration between French
      and Australian researchers engaged in participatory modeling and evaluation
      research. The framework seeks to assess the extent to which different
      participatory modeling initiatives not only modify perceptions among and
      interactions between participants, but also contribute to collective decision
      making. The article discusses the development of the framework and its
      application to three case-studies, two from Australia and one from the Pacific
      Island of the Republic of Kiribati. The article concludes with some comments for
      future use of the framework in a range of participatory modeling contexts.

PMID- 19847479
TI  - Assessing China's ecological restoration programs: what's been done and what
      remains to be done?
AB  - This article surveys the recent literature that has assessed China's ecological
      restoration programs, including the Sloping Land Conversion Program (SLCP) and
      the Natural Forest Protection Program (NFPP). Our presumption is that the
      performance of these programs should be determined by their effectiveness of
      implementation and significance of impact. Implementation effectiveness can be
      measured with such indicators as land area converted or conserved, and survival
      and stocking rates of restored vegetation, while impact significance can be
      gauged by the induced changes in ecosystem functionality and stability (erosion
      control, biodiversity protection, etc.) and socioeconomic conditions. Coupling
      this matrix with an exhaustive search of the publications, we find that: (1) the
      implementation effectiveness has not been examined as extensively as the impact
      significance; (2) efforts to assess the impact significance have concentrated on
      the SLCP, particularly its socioeconomic effects: growth of income, alternative
      industry, and employment, and likelihood of re-conversion; and (3) most of the
      socioeconomic studies are based on rural household surveys and discrete choice
      and difference in differences models. While much has been learned from previous
      studies, a lot more needs to be done in improving our understanding of the
      program execution and impacts. Future work should pay more attention to the NFPP
      and other programs, and the environmental impacts and the implementation
      effectiveness of all of them. To these ends, analysts must gather more field data
      regarding the evolving ecosystem conditions and socioeconomic information of
      higher aggregation, and conduct their research across scales and disciplines,
      with better application of geospatial technology and more effective modeling.

PMID- 19847480
TI  - Survey of emergency and surgical capacity in the conflict-affected regions of Sri
      Lanka.
AB  - BACKGROUND: Three decades of internal conflict in the North and East of Sri Lanka
      have taken a toll on the health care system in that area. METHODS: We proposed to
      quantify the current status of capacity to deliver emergency, anesthesia, and
      surgical interventions in the conflict affected areas of Sri Lanka. The World
      Health Organization (WHO) Tool for Situational Analysis to Assess Emergency and
      Essential Surgical Care (EESC) was used to evaluate 47 health facilities.
      RESULTS: Although most have trained health care providers capable of basic
      procedures, infrastructure and supplies were severely lacking. CONCLUSION: These
      data can be used as a basis for the recovery and rebuilding of EESC capacity in
      conflict-affected areas of Sri Lanka.

PMID- 19847481
TI  - Liver hydatid cyst with transdiaphragmatic rupture and lung hydatid cyst ruptured
      into bronchi and pleural space.
AB  - The aim of this case study is to present effectiveness of percutaneous drainage
      as a treatment option of ruptured lung and liver hydatid cysts. A 65-year-old
      male patient was admitted with complicated liver and lung hydatid cysts. A liver
      hydatid cyst had ruptured transdiaphragmatically, and a lung hydatid cyst had
      ruptured both into bronchi and pleural space. The patient could not undergo
      surgery because of decreased respiratory function. Both cysts were drained
      percutaneously using oral albendazole. Povidone-iodine was used to treat the
      liver cyst after closure of the diaphragmatic rupture. The drainage was
      considered successful, and the patient had no recurrence of signs and symptoms.
      Clinical, laboratory, and radiologic recovery was observed during 2.5 months of
      catheterization. The patient was asymptomatic after catheter drainage. No
      recurrence was detected during 86 months of follow-up. For inoperable patients
      with ruptured liver and lung hydatid cysts, percutaneous drainage with oral
      albendazole is an alternative treatment option to surgery. The percutaneous
      approach can be life-saving in such cases.

PMID- 19847482
TI  - MDCT versus MRI assessment of tumor response after transarterial
      chemoembolization for the treatment of hepatocellular carcinoma.
AB  - The purpose of this study was to compare the ability of multidetector computed
      tomography (MDCT) and magnetic resonance imaging (MRI) to evaluate treatment
      results after transarterial chemoembolization (TACE), with a special focus on the
      influence of Lipiodol on calculation of tumor necrosis according to EASL
      criteria. A total of 115 nodules in 20 patients (17 males, 3 females; 69.5 +/-
      9.35 years) with biopsy-proven hepatocellular carcinoma were treated with TACE.
      Embolization was performed using a doxorubicin-Lipiodol emulsion (group I) or DC
      Beads loaded with doxorubicin (group II). Follow-up included triphasic contrast
      enhanced 64-row MDCT (collimation, 0.625 mm; slice, 3 mm; contrast bolus, 120 ml
      iomeprol; delay by bolus trigger) and contrast-enhanced MRI (T1 native, T2
      native; five dynamic contrast-enhanced phases; 0.1 mmol/kg body weight gadolinium
      DTPA; slice thickness, 4 mm). Residual tumor and the extent of tumor necrosis
      were evaluated according to EASL. Contrast enhancement within tumor lesions was
      suspected to represent vital tumor. In the Lipiodol-based TACE protocol, MDCT
      underestimated residual viable tumor compared to MRI, due to Lipiodol artifacts
      (23.2% vs 47.7% after first, 11.9% vs 31.2% after second, and 11.4% vs 23.7%
      after third TACE; p = 0.0014, p < 0.001, and p < 0.001, respectively). In
      contrast to MDCT, MRI was completely free of any artifacts caused by Lipiodol. In
      the DC Bead-based Lipiodol-free TACE protocol, MRI and CT showed similar residual
      tumor and rating of treatment results (46.4% vs 41.2%, 31.9 vs 26.8%, and 26.0%
      vs 25.6%; n.s.). In conclusion, MRI is superior to MDCT for detection of viable
      tumor residuals after Lipiodol-based TACE. Since viable tumor tissue is
      superimposed by Lipiodol artifacts in MDCT, MRI is mandatory for reliable
      decision-making during follow-up after Lipiodol-based TACE protocols.

PMID- 19847483
TI  - Acinetobacter sp. Ud-4 efficiently degrades both edible and mineral oils:
      isolation and characterization.
AB  - A novel Acinetobacter strain, Ud-4, possessing a strong capacity to degrade
      edible, lubricating, and heavy oil was isolated from seawater in a fishing port
      located in Toyama, Japan. It was identified by morphological and physiological
      analyses and 16S rDNA sequencing. This strain could utilize five types of edible
      oils (canola oil, olive oil, sesame oil, soybean oil, and lard), lubricating oil,
      and C-heavy oil as the sole carbon source for growth in M9 medium. The strain
      grew well and heavily degraded edible oils in Luria-Bertani medium during a 7-day
      culture at 25 degrees C; it also degraded all kinds of oils in artificial
      seawater medium for marine bacteria. Furthermore, this strain was capable of
      degrading almost all C10-C25 n-alkanes in C-heavy oil during a 4-week culture.
      Oligonucleotide primers specific to two catabolic genes involved in the
      degradation of n-alkanes (Acinetobacter sp. alkM) and triglyceride (Acinetobacter
      sp. lipA) allowed amplification of these genes in strain Ud-4. To our knowledge,
      this is the first report on the isolation of a bacterium that can efficiently
      degrade both edible and mineral oils.

PMID- 19847484
TI  - Expression and purification of an antimicrobial peptide, bovine lactoferricin
      derivative LfcinB-W10 in Escherichia coli.
AB  - Antimicrobial peptides (AMPs) are extremely attractive candidate for therapeutic
      agents due to their wide spectrum of antimicrobial activity and action mechanism
      different from antibiotics. In this study, a method using genetic engineering for
      obtaining an antimicrobial peptide, bovine lactoferricin derivative peptide
      LfcinB-W10, has been developed. According to the coden usage of Escherichia coli,
      a gene encoding the peptide was synthesized and a recombinant vector of E. coli
      expression pGEX-EN-LFW was constructed. The LfcinB-W10 peptide fused with
      glutathione S-transferase (GST) was successfully expressed and about 20 mg fusion
      protein with 90% purity was obtained from 1 l culture. The recombinant LfcinB-W10
      (rLfcinB-W10) was released from fusion protein by the enterokinase digestion, and
      about the LfcinB-W10 yield reached 300 mug per 1 l culture. The purified rLfcinB
      W10 was found to have growth inhibition activity against Staphylococcus aureus
      (S. aureus) ATCC25923.

PMID- 19847486
TI  - Gender effects on airway closure in head and neck cancer patients.
AB  - Age, gender, and bolus effects on the duration of laryngeal closure, the onset of
      laryngeal closure in relation to the first cricopharyngeal opening, and the
      duration of cricopharyngeal opening in head and neck cancer patients have not
      been well documented. Thirty-three head and neck cancer patients (middle-aged
      women and men, and older women and men) were evaluated with videofluoroscopy
      before and 3 months after their cancer treatment. At 3 months post-treatment, the
      mean duration of laryngeal closure was longer for women than for men at 1-, 5-,
      and 10-ml bolus volumes. The duration of laryngeal closure at 3 months post
      treatment and the duration of cricopharyngeal opening at both pretreatment and 3
      months post-treatment increased as liquid bolus volume increased. Gender effects
      were observed in the duration of laryngeal closure during swallow. Bolus effects
      were observed in the duration of laryngeal closure and cricopharyngeal opening.

PMID- 19847564
TI  - The national cancer data base: past, present, and future.

PMID- 19847485
TI  - Helicobacter pylori: bacterial factors and the role of cytokines in the immune
      response.
AB  - Helicobacter pylori is a gram-negative micro-aerophilic bacterium that is widely
      distributed geographically and causes chronic gastritis, peptic ulcers, gastric
      adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Bacterial
      virulence factors play an important role, since the virulent strains are more
      aggressive and increase the risk of developing severe clinical manifestations; in
      addition, other determinant factors are the nutritional state and the immune
      response of the host. Studies on humans, non-human primates, and rodents have
      reported that regulating proteins of the Th1 phenotype predominate in the immune
      response to the bacterial infection. The cytokines produced by this phenotype,
      are not very effective in eradicating the microorganism and furthermore,
      contribute to gastro-duodenal pathogenesis. Gastric inflammation in patients
      infected with H. pylori has been characterized by increased production of IL-1,
      IL-6, IL-12, IL-18, TNF-alpha, and IFN-gamma. Many prophylactic and therapeutic
      strategies have been researched using experimental animals. The utilization and
      effectiveness of vaccination on humans requires more study.

PMID- 19847565
TI  - Resection margin and recurrence-free survival after liver resection of colorectal
      metastases.
AB  - BACKGROUND: Optimal margin width is uncertain because of conflicting results from
      recent studies using overall survival as the end-point. After recurrence, re
      resection and aggressive chemotherapy heavily affect survival time; the potential
      confounding effect of such factors has not been investigated. Use of recurrence
      free survival (RFS) may overcome this limitation. The aim of this study is to
      evaluate the impact of width of resection margin on RFS and site of recurrence
      after hepatic resection for colorectal metastases (CRM). METHODS: From a
      prospectively maintained institutional database (1/1999-12/2007) we identified
      314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed
      pathologic analysis of the surgical margin and complete follow-up imaging studies
      documenting disease status and site of recurrence, which was categorized as:
      resection margin (M(arg)), other intra-hepatic ((other)IH), lung (L) or other
      extra-hepatic ((other)EH). Recurrence-free estimation was the survival end-point.
      RESULTS: Median follow-up was 56.5 months. Two hundred and fifteen patients
      (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection
      margin was associated with an increased risk of M(arg) recurrence (P < 0.001).
      The presence of >or=2 metastases was the only factor increasing the risk of
      positive margins (P < 0.05). The width of the negative resection margin (>or=1 cm
      versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P =
      0.6). Node status of the primary tumour, and size and number of CRM were
      independent predictors of RFS. CONCLUSIONS: Tumour biology and not the width of
      the negative resection margin affect RFS.

PMID- 19847566
TI  - What is an adequate margin for breast-conserving surgery? Surgeon attitudes and
      correlates.
AB  - BACKGROUND: Re-excision is common in breast-conserving surgery (BCS), partly due
      to lack of consensus on margin definitions. A population-based surgeon sample was
      used to determine current attitudes toward margin width and identify
      characteristics associated with margin choice. METHODS: Breast cancer patients
      treated from 2005 to 2007 were identified from Los Angeles and Detroit
      Surveillance, Epidemiology, and End Results (SEER) registries. Pathology reports
      were used to identify their surgeons, who were surveyed (n = 418). Response rate
      was 74.6% (n = 312). Mean surgeon age was 51.9 years, 17.8% were female, and mean
      number of years in practice was 18.5. RESULTS: Wide variation in margin selection
      was noted among surgeons, and did not differ for invasive cancer and ductal
      carcinoma in situ (DCIS). In a scenario of T1 invasive cancer, 11% of surgeons
      endorsed margins of tumor not touching ink (TNTI), 42% of 1-2 mm, 28% of > or =5
      mm, and 19% >1 cm as precluding need for re-excision before radiotherapy. On
      multivariate analysis, having 50% or more of practice devoted to breast cancer
      independently predicted smaller margin choice (p = 0.03). For a patient with a
      1.4-cm grade 2 estrogen receptor (ER)-positive DCIS without radiotherapy (RT)
      planned, 3% of surgeons chose TNTI, 12% 1-2 mm, 25% > or =5 mm, and 61% >1 cm as
      sufficient without re-excision. In the scenario of DCIS without RT, breast
      specialization independently predicted larger margin choice (p = 0.03). Gender
      and years in practice were not predictive of margin choice. CONCLUSIONS: Wide
      variation in BCS margin definition exists. Variation is similar for invasive
      cancer and DCIS with RT, with more specialized surgeons choosing smaller margins.
      In DCIS without RT, more specialized surgeons favored larger margins. A
      standardized margin definition may significantly affect re-excision rates.

PMID- 19847567
TI  - Positive peritoneal washing cytology in multiple cavities can predict poor
      prognosis of advanced gastric cancer patients.
AB  - BACKGROUND: Positive peritoneal washing cytology (PWC) has been reported to be a
      poor prognostic factor for gastric cancer. Japanese gastric cancer
      classifications recommend PWC in Douglas' pouch for advanced gastric cancer.
      However, the sensitivity of PWC is relatively low. The goal of this study was to
      investigate whether PWC in multiple cavities increases its sensitivity to predict
      prognosis. METHODS: Between January 1996 and December 2006, a series of 992
      patients with gastric cancer underwent D2 gastrectomy with intraoperative PWC. Of
      the 992 patients, 62 patients had positive PWC. PWC was conducted in four
      cavities (left subphrenic cavity, right subhepatic cavity, Douglas' pouch, and
      inside the omental bursa). The 62 patients were retrospectively analyzed for
      their background and survival. RESULTS: Eleven (17.7%) patients had negative PWC
      in Douglas' pouch but were positive in the other cavities. The 62 patients were
      classified into two groups according to the number of positive PWC cavities: 20
      patients with one or two and 42 patients with three or four positive PWC
      cavities. No significant difference in clinicopathological features was observed
      between these two groups. However, the overall and progression-free survival
      rates of patients with one or two positive PWC cavities were significantly higher
      than those for patients with three or more positive PWC cavities. CONCLUSION: PWC
      in multiple cavities was more sensitive than only in one cavity. The number of
      positive cavities may indicate the grade of tumor spread in the peritoneum and
      predict the prognosis of patients with positive PWC.

PMID- 19847568
TI  - Chordoma of the mobile spine and sacrum: a retrospective analysis of a series of
      patients surgically treated at two referral centers.
AB  - BACKGROUND: Chordoma is a rare tumor, and its natural history is still not well
      known. MATERIALS AND METHODS: All patients affected by localized chordoma
      surgically treated at Istituto Ortopedico Rizzoli, Bologna, and Istituto
      Nazionale Tumori, Milan, Italy, between 1980 and 2008 were reviewed. Local
      recurrence, distant metastasis, and overall survival (OS) were analyzed both from
      time of diagnosis and from time of local recurrence/distant metastasis. A
      multivariable analysis to identify independent prognostic factors was carried
      out. RESULTS: A total of 138 consecutive patients were identified (sacrum 78%,
      lumbar spine 15%, cervical-dorsal spine 7%). Of these, 130 underwent surgical
      resection. Median follow-up was 142 months. The 5- and 10-year OS, local relapse
      free survival (LRFS), and distant relapse-free survival (DRFS) were,
      respectively, 78% and 54%, 52% and 33%, and 86% and 72%. Size was an independent
      prognostic factor for OS (P value < .001), LRFS (P value: .038), and DRFS (P
      value: .004), while surgical margins independently predicted LRFS (P value: .003)
      with a trend for OS. The 5- and 10-year OS, LRFS, and DRFS after the first local
      relapse were 50% and 26%, 47% and 31%, and 64% and 61%. The size of the
      recurrence and quality of surgical margins did not influence postrelapse OS. The
      5-year OS after the second local relapse was 19%. 22% of patients developed
      distant metastases with a 5-year post-metastases OS of 33%. CONCLUSIONS: Tumor
      size and surgical margins affected outcome only on initial presentation. However,
      wide surgery was feasible in a minority of cases. Most patients died of local
      regional disease even when metastases occurred. Indeed, long-term prognosis was
      such that disease-free survival at 10 years was only 26%.

PMID- 19847569
TI  - Local excision after preoperative chemoradiation results in an equivalent outcome
      to total mesorectal excision in selected patients with T3 rectal cancer.
AB  - BACKGROUND: We previously reported 26 patients who underwent preoperative
      chemoradiotherapy (CXRT) for T3 rectal cancer and were subsequently offered full
      thickness local excision (LE) as an alternative to total mesorectal excision
      (TME). At nearly 4 years' follow-up, no difference in outcome was observed. This
      study compares outcomes in a larger cohort of patients and reevaluates the
      original 26 patients after longer follow-up. METHODS: Retrospective review was
      performed of patients who underwent preoperative CXRT (radiation doses of 45,
      50.4, or 52.5 Gy with concurrent 5-fluorouracil-based chemotherapy) followed by
      surgery for T3 rectal cancer. Forty-seven patients underwent LE (Kraske [n = 6]
      or transanal excision [n = 41]). 473 patients underwent TME (abdominoperineal
      resection [n = 141] or low anterior resection [n = 332]). Local recurrence,
      disease-free survival (DFS), disease-specific survival, and overall survival (OS)
      rates were compared. RESULTS: Median follow-up was 63 months for the LE group and
      59 months for the TME group. Twenty-three LE patients (49%) had a complete
      response to CXRT, 17 (36%) had microscopic residual disease, and 7 (15%) had
      gross residual disease, compared with 108 (23%), 89 (19%), and 276 (58%) TME
      patients, respectively. There was no significant difference between the 10-year
      actuarial local recurrence rate for the LE group versus the TME group (10.6% and
      7.6%, respectively; P = .52), and no significant difference in DFS, disease
      specific survival, or OS rates between groups. CONCLUSIONS: In selected patients
      who demonstrate an excellent response to preoperative CXRT for T3 rectal cancer,
      full-thickness LE offers comparable local control, DFS, and OS to that achieved
      with proctectomy and TME.

PMID- 19847570
TI  - Total proctocolectomy with ileoanal J-pouch reconstruction utilizing the hand
      assisted laparoscopic approach.
AB  - This manuscript describes our technique for a minimally invasive ileoanal J-pouch
      procedure utilizing hand-assisted laparoscopy. We detail several important
      maneuvers that may be helpful to the surgeon faced with the challenge of a
      difficult laparoscopic pouch.

PMID- 19847571
TI  - Psychiatric factors and weight loss patterns following gastric bypass surgery in
      a veteran population.
AB  - BACKGROUND: Although pre-surgical psychological evaluations are commonly
      administered to patients considered for weight loss surgeries, the value of these
      evaluations for predicting weight loss success has been questioned. In this
      study, we addressed this issue by examining patient's total number of psychiatric
      indicators rather than individual psychological factors as predictors of weight
      loss/weight regain. METHODS: Sixty adult veterans completed gastric bypass
      surgery or laparoscopic gastric banding after completing a multidisciplinary
      evaluation for surgical clearance, including a psychological assessment. Patients
      were subsequently followed for 24 month to examine changes in weight, body mass
      index, and risk of weight regain. RESULTS: Nearly three fourths of the sample
      carried either a single (40.0%) or multiple psychiatric diagnoses (33.4%). Nearly
      half (47.5%) of the sample ceased losing weight after 1 year, with 29.5%
      regaining weight after this point. Neither psychiatric nor biomedical factors
      effectively predicted 1-year weight loss totals; however, we observed a
      significant linear relationship between the number of psychiatric factors and
      post-1-year weight changes (r = 0.33, p = 0.01). After adjusting for demographic
      and biomedical factors, patients with two or more psychiatric diagnoses were
      found to be significantly more likely to experience weight loss cessation or
      weight regain after 1-year (OR = 6.4, 95% CI = 1.3-12.4) relative to those with
      zero or one psychiatric diagnosis. CONCLUSIONS: Assessing mental health factors
      in terms of the total number of psychiatric conditions improved the prediction of
      weight loss surgery outcomes in this veteran sample. An expanded model for
      understanding how psychological factors may affect weight loss surgery may
      improve the utility of pre-bariatric psychological assessments.

PMID- 19847572
TI  - Impact of laparoscopic sleeve gastrectomy on iron indices: 1 year follow-up.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been recently introduced as
      a stand-alone, restrictive bariatric surgery. Theoretically, LSG attenuates
      micronutrients deficiencies and associated complications that typically observed
      following malabsorptive procedures. The aim of this study was to assess iron
      indices and the 1-year incidence of iron deficiency in patients undergoing LSG.
      METHODS: This was a prospective, cohort study; patients who underwent LSG from
      June 2007 to April 2008 at our institution were screened for inclusion.
      Preoperative hemoglobin and iron indices including serum iron, transferrin
      saturation, ferritin, and soluble transferrin receptor were compared to their
      levels at 6 and 12 months after surgery. Similarly, vitamin B12 and red blood
      cell (RBC) folate were analyzed as secondary end points. Weight parameters and C
      reactive protein (CRP) levels were compared before surgery and 1 year
      postoperatively. RESULTS: A total of 61 patients were included in the study. One
      year after surgery, there was a significant decrease in the mean body mass index
      from 47.5 +/- 9.6 to 30.5 +/- 6.5 (P < 0.001). The incidence of iron deficiency
      was 4.9% at both follow-up time points. Anemia was evident in 4.9% of patients 1
      year postoperatively. Significant decrease in the means of the natural logarithm
      of vitamin B12 and RBC folate were observed as early as 6 months after surgery (P
      = 0.014; P < 0.005, respectively). The decrease in mean CRP level 12 months
      postoperatively was statistically significant compared to its preoperative value
      (P < 0.0001). CONCLUSION: LSG is an effective procedure for the treatment of
      morbid obesity and its associated inflammatory state. One year after surgery,
      development of iron deficiency was insignificant.

PMID- 19847573
TI  - Roux-en-Y gastric bypass in an adolescent patient with Bardet-Biedl syndrome, a
      monogenic obesity disorder.
AB  - Bardet-Biedl syndrome (BBS) is a rare genetic disorder characterized by a wide
      range of phenotypic variability and associated with the development of life
      threatening obesity. Birth weight tends to be normal, but rapid weight gain
      begins after the first year, probably due to polyphagia rather than abnormalities
      in energy metabolism. A morbidly obese 16-year-old male patient with BBS was
      referred to our institution, after nonsurgical methods of weight control had
      failed, for surgical treatment of his obesity. His preoperative body mass index
      (BMI) was 52.28 kg/m(2) (height, 1.84 m; weight, 177 kg) and was above the 99th
      centile for age and gender. The patient underwent laparoscopic Roux-en-Y gastric
      bypass (RYGBP). The postoperative period was uneventful. Three and a half years
      after the operation, the patient's weight has decreased to 118 kg (BMI, 34.85
      kg/m(2)), while significant improvement in his hypertension, hyperuricemia, and
      mobility has been noted. In our BBS patient, RYGBP proved to be safe and
      effective; nevertheless, longer follow-up is required to evaluate the weight loss
      durability and to assess the lasting beneficial effect of surgical intervention
      on genetically determined co-morbidities.

PMID- 19847574
TI  - Vitamin A deficiency (VAD) after a duodenal switch procedure: a case report.
AB  - Vitamin A deficiency (VAD) after bariatric surgery is a well-documented
      complication. Clinical signs of VAD deficiency are significant if the vitamin A
      level is below 100 mug/L (4 mumol/L). Main symptom of VAD is nyctalopia. It has
      been described in several reports after malabsorptive bariatric procedures. We
      report a 52-year-old man with VAD complained of night blindness and optic
      neuropathy after undergoing a duodenal switch procedure. The case illustrates the
      necessity of lifelong vitamin supplementation after malabsorptive bariatric
      operations.

PMID- 19847575
TI  - Laparoscopic gastric banding without visible scar: a short series with
      intraumbilical SILS.
AB  - Single-incision laparoscopic surgery has been developed with the aims of further
      reducing the invasiveness of traditional laparoscopy. The technique of lap-band
      placement from a single intraumbilical incision is described. Three patients
      underwent a single-incision laparoscopic surgery gastric banding (SILS-GB) for
      morbid obesity from May to September 2008. All interventions were uneventful and
      patients were discharged on first postoperative day, after an upper
      gastrointestinal series. SILS-GB is virtually scarless intervention and may be
      performed as a day-surgery procedure for the treatment of morbid obesity.

PMID- 19847576
TI  - Midgut malrotation encountered during laparoscopic roux-en-y gastric bypass.
AB  - Unexpected midgut malrotation (MM) was encountered during laparoscopic Roux-en-Y
      gastric bypass for obesity. This procedure, being performed for the first time
      within our trust, was completed nonetheless without any postoperative
      complications. MM is a rare condition in adults, with a comprehensive literature
      review finding a paucity of reports of MM during bariatric procedures.

PMID- 19847577
TI  - Efficacy of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis.
AB  - PURPOSE: This study aimed to investigate the efficacy of ursodeoxycholic acid
      (UDCA) for Japanese patients with autoimmune hepatitis (AIH). METHODS: One
      hundred forty-seven patients were investigated. RESULTS: As initial treatment, 25
      patients received UDCA (300-600 mg/day) monotherapy (UDCA group), 40 received a
      combination of prednisolone (PSL) (>=20 mg/day) and UDCA (combination group), 68
      received PSL monotherapy (PSL group), and 14 received other treatments. During
      the follow-up, in the UDCA group, PSL was added to 8 of 12 patients failing to
      achieve the normalization of serum transaminase levels with UDCA monotherapy.
      Cumulative incidence of the normalization of serum transaminase levels was 64% in
      the UDCA group, 95% in the combination group, and 94% in the PSL group (log-rank
      test, P = 0.0001). UDCA group required longest periods until the normalization of
      serum transaminase levels. Eleven patients, who achieved persistent normalization
      of serum transaminase levels with UDCA monotherapy, did not reach liver failure
      or develop hepatocellular carcinoma for 49.7 (range = 13.4-137.3) months.
      Meanwhile, during the taper of PSL, doses of PSL at the initial relapse were
      lower in patients treated with PSL and UDCA than in those treated with PSL
      monotherapy, and initial relapse occurred earlier in patients treated with PSL
      monotherapy. CONCLUSIONS: UDCA monotherapy is effective for some Japanese AIH
      patients; however, UDCA monotherapy for patients with either high-grade
      inflammatory activity or poor residual capacity of liver function is not
      recommended because they may reach liver failure before achievement of remission.
      Meanwhile, additional use of UDCA during the taper of corticosteroids may be
      effective for the prevention of early relapse.

PMID- 19847578
TI  - Femoral revision hip arthroplasty: a comparison of two stem designs.
AB  - For various reasons the tapered, fluted, modular titanium (TFMT) stem has become
      our component of choice over cylindrical, nonmodular cobalt chrome (CNCC)
      components for THA revision. We therefore asked whether the TFMT femoral
      components better achieved three important goals of revision arthroplasty than
      CNCC stems: (1) improving quality of life; (2) avoiding complications; and (3)
      preserving or restoring femoral bone stock. We compared patients undergoing
      femoral component revision hip arthroplasty with either a CNCC (N = 105)
      component or a TFMT (N = 95) component to determine if the increased use of TFMT
      components is justified. We retrospectively reviewed all patients undergoing
      revision total hip arthroplasty between January 2000 and March 2006. All eligible
      patients completed outcome questionnaires (WOMAC, SF-12, Oxford-12, UCLA Activity
      Score, and Satisfaction Scores). Radiographs were evaluated for loosening and
      preservation or restoration of the proximal femur host bone. The TFMT and CNCC
      cohorts were comparable with respect to age, gender, diagnosis, and
      comorbidities. The TFMT cohort had worse preoperative bone defects (65% Paprosky
      3B and 4). The TFMT cohort had higher outcome scores (WOMAC pain, WOMAC
      stiffness, Oxford-12, and Satisfaction), fewer intraoperative fractures, and
      better restoration of the proximal femur host bone. Our data suggest the TFMT
      stem provided improved clinical outcomes (improved quality of life, decreased
      complications, and preservation of bone stock) than the CNCC stem. LEVEL OF
      EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19847579
TI  - Papers presented at the annual meetings of the Knee Society: editorial comment.

PMID- 19847581
TI  - The role of polyethylene design on postoperative TKA flexion: an analysis of 1534
      cases.
AB  - The range of motion after TKA depends on many patient, surgical technique, and
      implant factors. Recently, high-flexion designs have been introduced as a means
      of ensuring or gaining flexion after TKA. We therefore evaluated factors
      affecting postoperative flexion to determine whether implant design influences
      longterm flexion. We prospectively collected data on patients receiving a primary
      Genesis II total knee replacement with a minimum of 1-year followup (mean, 5.4
      years; range, 1-13 years). We recorded pre- and postoperative outcome measures,
      patient demographics, and implant design (cruciate retaining [CR, n = 160],
      posterior stabilized [PS, n = 1177], high-flex posterior stabilized [HF-PS, n =
      197]). Backward stepwise linear regression modeling identified the following
      factors affecting postoperative flexion: preoperative flexion, gender, body mass
      index, and implant design. Independent of gender, body mass index, and
      preoperative flexion, patients who received a HF-PS and PS design implant had a
      mean of 8 degrees and 5 degrees more flexion, respectively, than those who
      received a CR implant. Patients with low flexion preoperatively (<100 degrees)
      were more likely to gain flexion, whereas those with high flexion preoperatively
      (>120 degrees) were most likely to maintain or lose flexion postoperatively.
      Controlling for implant design, patients with high flexion preoperatively (>120
      degrees) were more likely to gain flexion with the HF-PS design implant (HF-PS =
      32.0%; PS = 15.1%; CR = 4.5%). LEVEL OF EVIDENCE: Level II, prognostic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 19847582
TI  - Correction and prevention of deformity in type II tibialis posterior dysfunction.
AB  - Cobb described a method of reconstruction in Johnson and Strom Type II tibialis
      posterior dysfunction (TPD) using a split tibialis anterior musculotendinous
      graft. We assessed patient function and satisfaction after a modified Cobb
      reconstruction in a group of patients with a narrow spectrum of dysfunction,
      examined a modification of the Johnson and Strom classification to emphasize
      severity of deformity, and assessed the ability of the technique to prevent
      subsequent fixed deformity. We prospectively followed 32 patients managed by this
      technique and a translational os calcis osteotomy with early flexible deformity
      after failed conservative treatment. There were 28 women and four men with
      unilateral disease. The average followup was 5.1 years. Staging was confirmed
      clinically and with imaging. The modified surgery involved a bone tunnel in the
      navicular rather than the medial cuneiform with plaster for 8 weeks followed by
      orthotics and physiotherapy. All of the osteotomies healed and 29 of the 32
      patients could perform a single heel rise test at 12 months. The mean
      postoperative American Orthopaedic Foot and Ankle Society hindfoot score was 89.
      One patient had a superficial wound infection and one a temporary dysesthesia of
      the medial plantar nerve; both resolved. The observations suggest the technique
      is a comparable method of treating early Johnson and Strom Type II TPD. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19847583
TI  - Posterior displacement of the tibia increases in deep flexion of the knee.
AB  - BACKGROUND: Deep knee flexion is important to proper function for some activities
      and in some cultures, although there are large posterior forces during high knee
      flexion. Most of what we know about posterior restraint and stability, however,
      has not been determined from deep flexion and without distinguishing motion in
      the medial and lateral compartments. QUESTIONS/PURPOSES: We therefore evaluated
      (1) the difference in posterior displacement between the medial and lateral
      compartments at a commonly used flexion angle of 90 degrees ; (2) that of deeply
      flexed knees at 135 degrees ; and (3) the difference in kinematics in the medial
      and lateral compartments. We analyzed posterior stability in 21 normal knees
      using interventional open magnetic resonance imaging (MRI) system. RESULTS: When
      manual posterior stress was applied, the posterior displacements of the tibia
      were 0.6 mm/2.1 mm (medial/lateral) at 90 degrees and 0.6 mm/3.6 mm at 135
      degrees . The posterior aspect of the femoral medial condyle moved 7.5 mm
      anteriorly with knee flexion, whereas the lateral condyle moved 1.3 mm
      anteriorly. The contact point of the lateral compartment moved 9.2 mm posteriorly
      with knee flexion, whereas the contact point of the medial compartment moved 2.3
      mm anteriorly. CONCLUSIONS: Posterior displacement was larger in the lateral
      compartment at both flexion angles with manual posterior stress. As the knees
      flexed from 90 degrees to 135 degrees , posterior displacement became larger in
      the lateral compartment. CLINICAL RELEVANCE: Cruciate-retaining total knee
      arthroplasty (TKA) or posterior cruciate ligament (PCL) reconstruction surgery
      should aim to achieve stability on the medial side and a few millimeters of
      laxity at the lateral side at 90 degrees flexion with increasing laxity only on
      the lateral side in deep flexion.

PMID- 19847584
TI  - What distinguishes weight-loss maintainers from the treatment-seeking obese?
      Analysis of environmental, behavioral, and psychosocial variables in diverse
      populations.
AB  - BACKGROUND: Understanding the factors that influence successful weight control is
      critical for developing interventions. PURPOSE: The purpose of the study was to
      provide a comprehensive understanding of the role of psychosocial, environmental,
      and behavioral variables in distinguishing weight-loss maintainers (WLM) from
      treatment-seeking obese (TSO). METHODS: WLM (n = 167) had lost > or =10% of their
      maximum body weight, had kept the weight off for > or =5 years, and were now of
      normal weight. TSO-1 and TSO-2 had a history of dieting and body mass index > or
      =25. TSO-1 was predominantly Caucasian; TSO-2 was predominantly African-American.
      Bayesian model averaging was used to identify the variables that distinguished
      WLM from TSO-1 and TSO-2. RESULTS: The variables that most consistently
      discriminated WLM from TSO were more physical activity (ORs = 3.95 and 2.85),
      more dietary restraint (ORs = 1.63 and 1.41), and less dietary disinhibition (ORs
      = 0.69 and 0.83). Environmental variables, including the availability of physical
      activity equipment, TVs, and high-fat foods in the home, also distinguished WLM
      from TSO. CONCLUSIONS: Obesity treatment should focus on increasing conscious
      control over eating, engaging in physical activity, and reducing disinhibition.
      Changes in the home environment may help facilitate these behavioral changes.

PMID- 19847587
TI  - Cerebral cortical gene expression in acutely anemic rats: a microarray analysis.
AB  - PURPOSE: Hemodilution in perioperative patients has been associated with
      neurological morbidity and increased mortality by undefined mechanisms. This
      study assesses whether hemodilutional anemia up-regulated inflammatory cerebral
      gene expression (microarray) to help define the mechanism. METHODS: Hemodilution
      was performed in anesthetized rats by exchanging 50% of the estimated blood
      volume (30 mL kg(-1)) with pentastarch. Two groups of control animals were
      utilized, i.e., a non-anesthetized control (Normal Control) and an anesthetized
      control group (Anesthesia Control). Blood pressure, hemoglobin concentration, and
      arterial blood gas analysis were performed before and after hemodilution.
      Cerebral cortex was harvested from isoflurane-anesthetized rats (n = 6) after 6
      and 24 hr of recovery and was used to perform complimentary DNA (cDNA) microarray
      analyses. Pro-inflammatory chemokine and cytokine protein levels were also
      measured. RESULTS: Microarray analysis demonstrated up-regulation of 72 and 27
      genes (6 and 24 hr, respectively) in anemic cerebral cortex. These genes were
      involved in a number of biological functions, including (1) inflammatory
      responses; (2) angiogenesis; (3) vascular homeostasis; (4) cellular biology; and
      (5) apoptosis. Chemokine ribonucleic acid (RNA) expression (CXCL-1, -10, and -11)
      was highest in anemic brain tissue (P < 0.0125 for each). Protein measurements
      demonstrated a significant increase in interleukin-6, tumor necrosis factor
      alpha, and monocyte chemoattractant protein-1 (P < 0.05 for each). CONCLUSION:
      This study utilizes microarray technology to elucidate changes in cerebral
      cortical gene expression in response to acute hemodilution. These findings
      demonstrate an increase in pro-inflammatory chemokines (RNA, protein) and
      cytokines (protein). An improved understanding of the inflammatory response to
      anemia may help to minimize associated morbidity and mortality.

PMID- 19847585
TI  - Synaptic inhibition, excitation, and plasticity in neurons of the cerebellar
      nuclei.
AB  - Neurons of the cerebellar nuclei generate the non-vestibular output of the
      cerebellum. Like other neurons, they integrate excitatory and inhibitory synaptic
      inputs and filter them through their intrinsic properties to produce patterns of
      action potential output. The synaptic and intrinsic features of cerebellar
      nuclear cells are unusual in several respects, however: these neurons receive an
      overwhelming amount of basal and driven inhibition from Purkinje neurons, but are
      also spontaneously active, producing action potentials even without excitation.
      Moreover, not only is spiking by nuclear cells sensitive to the amount of
      inhibition, but the strength of inhibition is also sensitive to the amount of
      spiking, through multiple forms of long-term plasticity. Here, we review the
      properties of synaptic excitation and inhibition, their short-term plasticity,
      and their influence on action potential firing of cerebellar nuclear neurons, as
      well as the interactions among excitation, inhibition, and spiking that produce
      long-term changes in synaptic strength. The data provide evidence that electrical
      and synaptic signaling in the cerebellar circuit is both plastic and resilient:
      the strength of IPSPs and EPSPs readily changes as the activity of cerebellar
      nuclear cells is modified. Notably, however, many of the identified forms of
      plasticity have an apparently homeostatic effect, responding to perturbations of
      input by restoring cerebellar output toward pre-perturbation values. Such forms
      of self-regulation appear consistent with the role of cerebellar output in
      coordinating movements. In contrast, other forms of plasticity in nuclear cells,
      including a long-term potentiation of excitatory postsynaptic currents (EPSCs)
      and excitation-driven increases in intrinsic excitability, are non-homeostatic,
      and instead appear suited to bring the circuit to a new set point. Interestingly,
      the combinations of inhibitory and excitatory stimuli that potentiate EPSCs
      resemble patterns of activity predicted to occur during eyelid conditioning,
      suggesting that this form long-term potentiation, perhaps amplified by intrinsic
      plasticity, may represent a cellular mechanism that is engaged during cerebellar
      learning.

PMID- 19847588
TI  - Innovations in anesthesia education: the development and implementation of a
      resident rotation for advanced airway management.
AB  - PURPOSE: This article incorporates the following objectives: to review the
      current evidence regarding the occurrence and management of difficult airways, to
      outline the role for alternative technology in the management of the difficult
      airway, to provide a rationale for structured airway rotations in anesthesia
      residency training, to discuss the barriers to establishing the rotations, to
      outline issues that must be considered and resolved to enhance these rotations,
      and to share the experience we have gained over the last decade of offering an
      airway rotation in the Department of Anesthesiology at the University of Ottawa.
      PRINCIPAL FINDINGS: The incidence of difficult laryngoscopy and intubation has
      not changed in recent times. Persistent attempts at direct laryngoscopy are
      associated with low success rates and patient complications. The early use of
      alternative devices improves the likelihood of success in airway management and
      reduces the potential for patient injury. Alternative airway management devices
      are increasingly available to Canadian anesthesiologists, and there is an
      expectation that anesthesiologists will possess the necessary skills to safely
      manage the difficult airway with these alternative devices. CONCLUSIONS:
      Anesthesia training programs must provide residents with the skill sets necessary
      for safe independent practice in airway management. The changes in the scope and
      reality of residency training have exposed limitations in the traditional
      mentoring model of residency training; consequently, many programs have responded
      by offering sub-specialty rotations. In particular, advanced airway management
      rotations are being offered increasingly to residents in the Canadian training
      programs. Considerations and strategies to develop and implement a structured
      airway management program during anesthesia residency are discussed.

PMID- 19847589
TI  - Always consider left ventricular outflow tract obstruction in hemodynamically
      unstable patients.

PMID- 19847590
TI  - Adult onset Still's disease diagnosed concomitantly with occult papillary thyroid
      cancer: paraneoplastic manifestation or coincidence?
AB  - Adult onset Still's disease (AOSD) is an inflammatory disease of unknown
      etiology, characterized by spiking fever, evanescent salmon pink maculopapular
      rash, arthritis, and leukocytosis with neutrophilia. Malignant lymphoma is one of
      the most important differential diagnoses of AOSD. AOSD has been reported as one
      of paraneoplastic syndromes associated with breast cancer. We report a rare case
      of occult papillary thyroid cancer (PTC) diagnosed coincidently with AOSD. A 32
      year-old woman was diagnosed with AOSD according to the diagnostic criteria of
      Yamaguchi as follows: leukocytosis with neutrophilia, high fever with 39 degrees
      C and above, arthralgia/arthritis, sore throat, liver dysfunctions, and
      lymphadenopathy. Excisional biopsy of cervical lymph node showed metastatic
      papillary carcinoma, and immunohistochemical staining for thyroglobulin and
      thyroid transcription factor-1 was strongly positive. There was no evidence of
      focal lesion in the thyroid glands. To our knowledge, this is the first report of
      adult onset Still's disease diagnosed concomitantly with occult PTC.

PMID- 19847591
TI  - Early experience of a fall and fracture prevention clinic at Mayo General
      Hospital.
AB  - BACKGROUND: Falls in the elderly are a significant public health problem.
      Previous studies have shown that most falls are multifactorial and an efficacious
      way of reducing the risk of falling is provided by a falls clinic. AIMS: A falls
      clinic runs every 2 weeks at Mayo General Hospital; we report on the activity of
      this clinic during its first year. METHODS: We performed a chart review and
      collected the following data. Thirty-seven patients attended the clinic. All
      patients were seen by a physiotherapist, occupational therapist, physician and
      pharmacist. Six patients had a further fall within a 12-month period; 2 of these
      suffered a further fracture. No patients were readmitted to hospital.
      CONCLUSIONS: The results show a reduction in fall occurrence from previously
      reported rates in this at-risk population. We find the falls clinic a convenient
      and effective method of managing elderly people who are at increased risk of
      falling.

PMID- 19847592
TI  - Periprosthetic fractures may be more likely in cementless femoral stems with
      sharp edges.
AB  - BACKGROUND: Many contour designs have been developed to improve the femoral stem
      in cementless total hip arthroplasty. AIMS: To assess the initial interfacial
      micromotion and stress distribution. METHODS: The prosthesis-bone interfacial
      micromotions and stress distributions of four commonly used femoral stems were
      assessed by finite element simulation: Alloclassic, Ribbed Anatomic, VerSys, and
      Secur-Fit. The proximal interfacial micromotions and stress distributions were
      calculated under the loading conditions of stair climbing. Three-dimensional
      micromotions were calculated in three proximal sections distal to the osteotomy
      level with 400 mm between each section. Medial, anterior, lateral and posterior
      points in each section were selected for calculations. RESULTS: The micromotions
      were <100 microm at all the selected points. Significant stress was detected
      along the sharp corners and ribs of the Alloclassic and Ribbed Anatomic stems,
      respectively. CONCLUSIONS: Significant stresses are associated with the stems
      with sharp edges.

PMID- 19847594
TI  - Abstracts of Laser Florence 2009, 23th International Congress Laser Medicine &
      IALMS Courses and the 3rd Biannual Congress of the International Photo Therapy
      Association. November 6-7, 2009. Florence, Italy.

PMID- 19847593
TI  - Minimally-invasive total hip arthroplasty will improve early postoperative
      outcomes: a prospective, randomized, controlled trial.
AB  - BACKGROUND: The rehabilitation of patients for total hip arthroplasty is
      unsatisfactory, especially the prolonged rehabilitation. AIMS: To explore
      indications and key points of anterolateral minimally-invasive total hip
      arthroplasty. METHODS: 110 patients admitted for unilateral total hip
      arthroplasty were randomly selected for surgery with either anterolateral
      minimally-invasive incision or standard posterolateral incision. Demographic
      data, perioperative index and postoperative function index were recorded and
      statistically analyzed. RESULTS: No significant difference was detected in
      operation time, abduction angle, anteversion angle, stem alignment and stem
      fixation. The incision length, blood loss, perioperative transfusion and 100-mm
      VAS score at the first 24 h in minimally-invasive group were significantly lower.
      The Harris hip score and Barthel index were significantly higher in minimally
      invasive group at 3 months' follow-up, but not significantly different 3 years
      after operation. CONCLUSIONS: There are fewer traumas, fewer blood losses and
      more rapid recovery in this approach.

PMID- 19847595
TI  - Optical coherence tomographic evaluation of the outer retinal architecture in
      Oguchi disease.
AB  - BACKGROUND: To report the changes in the optical coherence tomography (OCT)
      images of the outer retinal layers after prolonged dark adaptation in a patient
      with Oguchi disease. CASE: A 75-year-old woman showed the typical golden-yellow
      fundus reflex of Oguchi disease, and the coloration returned to normal after
      prolonged dark adaptation. Fourier domain OCT (FD-OCT) was performed on the
      patient's left eye before and after prolonged dark adaptation. OBSERVATIONS:
      Before dark adaptation, the FD-OCT images at the fovea had three identifiable
      reflection bands, namely, the external limiting membrane (ELM), the border
      between the photoreceptor inner and outer segments (IS/OS line), and the retinal
      pigment epithelium (RPE)/Bruch band. The paramacular area had only the ELM and
      RPE/Bruch bands. After 4 h of dark adaptation, the IS/OS line was also detected
      in the paramacular area. CONCLUSIONS: The absence of the IS/OS line in the
      extramacular regions in the partly dark adapted condition was most likely due to
      a defect in the rod photoreceptors of this area. The emergence of the IS/OS line
      after prolonged dark adaptation suggests that microarchitectural changes occur in
      the photoreceptors and that the changes may be correlated with the improvement of
      rod function.

PMID- 19847596
TI  - Congenital rotated macula with good vision and binocular function.
AB  - BACKGROUND: Two patients presented with congenital rotated macula with good
      vision and binocular function. CASES: Two patients had retinal folds with an
      extremely rotated macula OD as the result of peripheral fibrous proliferation on
      the retina. Each macula was substantially rotated to the nasal border of the
      disc. OBSERVATIONS: A 3-year-old girl (case 1) with best-corrected visual acuity
      (VA) of 0.5 OD and 1.0 OS was treated for amblyopia, after which she successfully
      achieved 1.0 bilaterally as well as good stereopsis of 120 seconds of arc
      measured with the TNO test. A 6-year-old girl (case 2) obtained a VA of 0.7 OD
      and 1.0 OS, and her stereopsis was of 240 seconds of arc. CONCLUSIONS: Good VA
      and stereopsis may be achieved by adaptation in the brain and an extremely large
      fusional potential at an early infantile age or a gradual shift of the macula.
      Appropriate treatment of amblyopia should be performed in patients with rotated
      macula if the macula appears normal.

PMID- 19847597
TI  - Ishihara test in 3- to 6-year-old children.
AB  - PURPOSE: To investigate the efficacy of a modified Ishihara color test in
      preschoolers. METHODS: The Ishihara test was performed to screen 115 children 3
      to 6 years of age for color vision deficiency. Children who could not read
      numbers were instructed to trace the shapes of the numbers and of colored winding
      lines on the test plates using a cotton-tipped applicator. The ability of the
      children to understand and complete the test was investigated. RESULTS: The
      Ishihara test was satisfactorily taken by 96.5% of the 115 children. Two 3-year
      olds and two 4-year-olds did not understand the test. Thirty-five percent of the
      3-year-olds could not read numbers but successfully used the tracing method.
      Three of the 51 boys and none of the 64 girls were considered color deficient.
      CONCLUSION: The modified Ishihara test was successfully performed by children
      aged 3 to 6.

PMID- 19847598
TI  - Aspheric laser in situ keratomileusis for the correction of myopia using the
      technolas 217z100: comparison of outcomes versus results from the conventional
      technique.
AB  - PURPOSE: To compare postoperative outcomes of a new aspheric laser in situ
      keratomileusis (LASIK) system, which applies an index for corneal asphericity (Q
      value), with outcomes of the conventional LASIK procedure. METHODS: Twenty-eight
      eyes of 15 consecutive patients (mean age, 36.4 +/- 5.8 years) underwent aspheric
      LASIK (As-LASIK group), and 33 eyes of 18 consecutive patients (mean age, 32.9 +/
      8.3 years) underwent conventional LASIK (Con-LASIK group) at Sanno Hospital
      (Tokyo, Japan). Both procedures were performed with a Moria LSK-One microkeratome
      and a Bausch and Lomb Technolas 217-z100 excimer laser. Preoperative mean
      spherical equivalent refraction values were -5.13 +/- 1.23 diopters (D) and -5.63
      +/- 0.88 D in the As-LASIK and Con-LASIK groups, respectively. Higher order
      aberrations were measured and contrast sensitivity was assessed at 3 months after
      the procedure, and these, along with safety, efficacy, and predictability, were
      compared between the two procedures. RESULTS: Conventional LASIK significantly
      increased higher order aberrations and reduced contrast sensitivity, whereas As
      LASIK did not increase spherical-like aberrations or alter contrast sensitivity.
      CONCLUSIONS: Aspheric LASIK may be a better laser technique than Con-LASIK, with
      less postoperative increase in spherical-like aberrations and better control over
      contrast sensitivity.

PMID- 19847599
TI  - Efficacy of substance P and insulin-like growth factor-1 peptides for preventing
      postsurgical superficial punctate keratopathy in diabetic patients.
AB  - PURPOSE: The efficacy of eyedrops containing peptides based on substance P (FGLM
      amide) and insulinlike growth factor-1 (SSSR) for prevention of superficial
      punctate keratopathy (SPK) after cataract surgery in individuals with type 2
      diabetes was examined. METHODS: Twenty-nine patients (29 eyes) with diabetes were
      enrolled in a double-masked, prospective, randomized, placebo-controlled clinical
      study. They were randomly assigned to one of two groups that received eyedrops
      containing either FGLM-amide and SSSR (n = 14) or phosphate-buffered saline (n =
      15) four times a day for 14 days starting 1 day after phacoemulsification. SPK
      scores (area, density, and combined area and density) were determined before as
      well as 1, 3, 7, and 14 days after surgery as main outcome measures. RESULTS: SPK
      scores did not differ between the two groups before surgery or before initiation
      of treatment. At day 2 after treatment initiation, all SPK scores were
      significantly lower in the FGLM-amide/SSSR group than in the control group. The
      density score was also significantly lower in the former group at day 7 after
      surgery. All scores returned to preoperative levels by day 14 after surgery in
      both groups. CONCLUSIONS: Eyedrops containing FGLM-amide and SSSR were effective
      for the prevention of SPK after cataract surgery in diabetic patients.

PMID- 19847600
TI  - A multicenter study on the health-related quality of life of cataract patients:
      baseline data.
AB  - PURPOSE: This study examines the impact of cataracts on health-related quality of
      life (HR-QOL) and health events in the older population. METHODS: The study
      population consisted of 439 unoperated cataract patients aged 60 years or older
      who visited any of the facilities affiliated with the Cataract Survey Group of
      the National Hospital Organization of Japan, which has been conducting a
      prospective multicenter cohort study on cataract patients. HR-QOL of the patients
      was assessed using the Japanese version of Visual Function Questionnaire-25 (VFQ
      25) and the 8-Item Short-Form Health Survey (SF-8). The health condition and
      health events of the patients were also investigated. RESULTS: The average age of
      the 439 patients enrolled (126 men and 313 women) was 73.0 +/- 7.1 years. There
      were 323 patients with comorbidities (73.6%), 81 of whom (23.7%) felt it was hard
      to visit the hospital owing to their visual impairment. In the previous year, 74
      patients (16.9%) had experienced a fall and 14 (3.2%) had been in a traffic
      accident. Of those, 43.2% and 8.3% respectively answered that the falls and the
      accident could have been triggered by their visual impairment. When the patients
      were classified according to visual acuity, most of the VFQ-25 subscale scores
      declined significantly with decreasing visual acuity, whereas the SF-8 scores
      showed no significant change. CONCLUSIONS: The participants of this study were
      patients with unoperated cataract, and thus the decline of HR-QOL was modest. The
      survey of health events, however, revealed that the visual constraint has a
      certain impact on the daily lives of the older population.

PMID- 19847601
TI  - Relationship between central corneal thickness and visual field defect in open
      angle glaucoma.
AB  - PURPOSE: To explore the relationship between central corneal thickness (CCT) and
      visual field defect in open-angle glaucoma (OAG). METHODS: In this cross
      sectional study, we tested 344 eyes in 344 eligible patients, including 233 with
      normal-tension glaucoma (NTG) and 111 with primary open-angle glaucoma (POAG).
      The association among variables, especially that between visual field defect and
      CCT, was probed by multivariate regression in eyes with NTG or POAG, and in all
      eyes. All eyes were divided into early, moderate, or severe visual field defect
      groups according to Anderson's classification. Statistical analysis was performed
      for all cases, and for the three CCT groups. RESULTS: Multivariate regression
      analysis revealed an association between CCT and visual field defect in eyes with
      NTG but not in eyes with POAG or in all eyes. The eyes with early visual field
      defect had greater CCT than did those with severe visual field defect (533.2
      versus 519.0 microm). The eyes with greater CCT had better visual field indices
      than did those with thinner CCT (-6.91 versus -9.17 dB). CONCLUSIONS: Central
      corneal thickness is a factor associated with the status of the visual field
      defect: a greater CCT is associated with a better visual field index. Other
      factors such as the glaucoma subtype play a role in the effect of CCT on visual
      field defect.

PMID- 19847602
TI  - Glaucoma diagnostic performance of humphrey matrix and standard automated
      perimetry.
AB  - PURPOSE: To evaluate and compare the performance of Humphrey Matrix perimetry
      (Matrix) and standard automated perimetry (SAP) for glaucoma discrimination.
      METHODS: Forty-seven healthy and 68 glaucomatous subjects were included in this
      study. Glaucoma was defined as having a glaucomatous optic disc and a nerve fiber
      indicator (NFI) GDx VCC scanning laser polarimetry score of >40. Glaucomatous
      subjects were classified into two groups, early (40 < NFI < or = 50) and moderate
      to advanced (NFI > 50). The number of clusters on Matrix and SAP pattern
      deviation maps were estimated and scored. Areas under the receiver operating
      characteristic curves (AUCs) of the cluster scores were calculated for early and
      moderate to advanced stages of glaucoma and compared between Matrix and SAP.
      RESULTS: Among 68 glaucomatous subjects, 24 eyes were classified as having early
      and 44 eyes as having moderate to advanced glaucoma. The overall AUC of the
      Matrix cluster score was comparable to that of SAP (0.857, 0.881, P = 0.538). The
      AUC of the cluster score did not reveal statistically significant differences
      between Matrix and SAP for either early or moderate to advanced stages of
      glaucoma (P = 0.831, 0.237). CONCLUSION: Both Matrix and SAP showed good
      diagnostic performance with glaucoma defined as structural loss. Matrix and SAP
      data showed similar discrimination capability for different stages of glaucoma
      determined by cluster analysis.

PMID- 19847603
TI  - Prophylactic vitrectomy for acute retinal necrosis.
AB  - PURPOSE: To evaluate the efficacy of prophylactic vitrectomy for acute retinal
      necrosis. METHODS: The clinical charts of 17 patients (18 eyes) with acute
      retinal necrosis and no retinal break or rhegmatogenous retinal detachment (RRD)
      were retrospectively analyzed for the efficacy of prophylactic vitrectomy. The
      retinal necrotic lesions at the initial presentation were classified into three
      groups according to the lesion site as described by Holland: zone 1 (posterior
      pole; n = 3), zone 2 (midperiphery; n = 12), and zone 3 (periphery; n = 3). All
      patients were treated with intravenous antiviral therapy. Three zone 1 eyes and
      eight zone 2 eyes underwent prophylactic vitrectomy. Four zone 2 eyes and three
      zone 3 eyes did not receive prophylactic vitrectomy. RESULTS: All zone 1 eyes
      developed RRD despite prophylactic vitrectomy. Among the 12 zone 2 eyes, eight of
      the eyes that underwent prophylactic vitrectomy did not develop RRD, whereas
      three of the four zone 2 eyes without prophylactic vitrectomy developed RRD. All
      zone 3 eyes were cured with only antiviral medication. CONCLUSIONS: Prophylactic
      vitrectomy is effective in preventing the development of RRD in eyes where
      necrotic lesions do not extend beyond the midperiphery (zone 2).

PMID- 19847604
TI  - Seroprevalence of Bartonella henselae in patients with uveitis and healthy
      individuals in Tokyo.
AB  - PURPOSE: To compare the seroprevalence of Bartonella henselae, a pathogen of cat
      scratch disease, in patients with uveitis and in healthy individuals. METHODS:
      Serum samples were collected from 197 consecutive patients with various entities
      of uveitis at Tokyo Medical and Dental University Hospital, and from 83 healthy
      age- and sex-matched volunteers. Anti-Bartonella IgG and IgM antibodies were
      examined by indirect immunofluorescent antibody. RESULTS: Serum antibodies to B.
      henselae were positive in 39 of 197 (19.8%) patients with uveitis, and in 21 of
      83 (25.3%) of the healthy volunteers. There was no statistical difference in the
      seroprevalence between the two groups. The overall seroprevalence of B. henselae
      was 60 of 280 (21.4%). CONCLUSIONS: The seroprevalence of B. henselae was similar
      in both patients with uveitis and in healthy volunteers in Tokyo, Japan. These
      data indicate that a significant number of healthy individuals are asymptomatic
      carriers of B. henselae, which should be kept in mind when a diagnosis of cat
      scratch disease is made.

PMID- 19847605
TI  - Sectoral thinning of the retina after branch retinal artery occlusion.
AB  - PURPOSE: We studied the temporal aspects of retinal thickness in eyes with branch
      retinal artery occlusion (BRAO) to demonstrate the retinal thinning process
      subsequent to the acute stage of the disease. METHODS: We studied the retinal
      thickness map obtained with optical coherence tomography (OCT) in nine eyes of
      nine patients with BRAO. Central foveal thickness and average retinal thickness
      in the superior or inferior sectors of the inner macula (IM) and outer macula
      (OM) were measured several times after the onset of BRAO. RESULTS: All follow-up
      data combined from the eyes with the occluded branch artery on the same vertical
      side showed a common pattern of decrease in the retinal thickness in the affected
      superior or inferior sectors of the IM and OM, which was described by an
      exponential decay curve, whereas few changes were seen in central foveal
      thickness. The fitting of the reducing retinal thickness curves to an exponential
      decay curve led to the final estimated thickness in the affected sectors of 60%
      that of the control. CONCLUSION: The initially thickened retina in the vertical
      sectors of the macula in eyes with BRAO decreases exponentially to a final
      thickness of 60% of that the normal retina.

PMID- 19847606
TI  - Expression of inhibin alpha by stromal cells of retinal angiomas excised from a
      patient with von Hippel-Lindau disease.
AB  - BACKGROUND: To report the results of immunohistochemical analyses of a retinal
      angioma obtained from a patient with von Hippel-Lindau (VHL) disease. CASE: A 13
      year-old girl with VHL disease presented with bilateral retinal angiomas and
      decreased vision in the right eye. Although transpupillary thermotherapy was
      performed to treat the angiomas, the tractional and exudative retinal detachment
      progressed OD, requiring vitreous surgery. Intraoperatively, a large retinal
      angioma was excised together with the surrounding retina to aid in reattaching
      the retina. The excised tissue was prepared for standard histopathology and
      immunohistochemistry. OBSERVATIONS: Histological examination showed that the
      excised tissue was made up of highly vascularized cells, and the retina was
      gliotic. The stromal cells had intracytoplasmic vacuoles and were located between
      the numerous vessels. These findings are identical to those of a
      hemangioblastoma. The stromal cells stained positively for vascular endothelial
      growth factor and neuron specific enolase, and weakly for glial fibrillary acidic
      protein. Some of the stromal cells stained positively for inhibin alpha. Isolated
      erythropoietin-positive cells, indicative of developmentally arrested
      angioblasts, were observed among the endothelial cells. CONCLUSIONS: The results
      indicate that stromal cells in retinal angiomas are neuroectodermal in origin
      with immunohistochemical features, for example, inhibin alpha, similar to
      cerebellar hemangioblastomas and renal cell carcinomas associated with VHL
      disease.

PMID- 19847607
TI  - Comparative outcomes of pars plana vitrectomy in acute postoperative
      endophthalmitis with 25-gauge and 20-gauge techniques.
AB  - PURPOSE: To evaluate the safety and outcomes of 25-gauge pars plana vitrectomy
      (PPV) in the treatment of postoperative endophthalmitis and compare it with 20
      gauge PPV. METHODS: The medical records of all patients diagnosed with acute
      endophthalmitis following cataract surgery who underwent PPV between December
      2000 and December 2007 were reviewed. Main outcome measures included final visual
      acuity (VA), additional interventions, and both intraoperative and postoperative
      complications. RESULTS: Records of 70 eyes of 70 patients with a condition
      diagnosed as postoperative endophthalmitis were evaluated. Fifty-eight eyes
      underwent 20-gauge PPV (group 1), and 12 eyes underwent 25-gauge PPV (group 2).
      Mean follow-up time for group 1 was 9.6 +/- 8.8 months, and for group 2, 7.9 +/-
      12.7 months (P = 0.57). Median VA at presentation was hand motion in both groups.
      The differences between the two groups in frequencies of visual outcome levels of
      20/800 and 20/100 were significant in favor of group 2 (20/800, P = 0.006;
      20/100, P = 0.01). In group 2, fewer additional interventions were required, and
      postoperative complications tended to be less frequent. CONCLUSIONS: Twenty-five
      gauge PPV seems to be safe and effective in the management of postoperative
      endophthalmitis. This sutureless technique may have some advantages over 20-gauge
      surgery, but controlled studies are needed to confirm the results.

PMID- 19847608
TI  - Effect of combined treatment with sub-Tenon injection of triamcinolone acetonide
      and photodynamic therapy in Japanese patients with age-related macular
      degeneration.
AB  - PURPOSE: To evaluate the benefit of the combination of a single sub-Tenon
      injection of triamcinolone acetonide (STTA) with photodynamic therapy (PDT) for
      the treatment of age-related macular degeneration (AMD) in Japanese patients.
      METHODS: The medical records of 111 eyes of 111 patients were reviewed
      retrospectively. Forty-five eyes underwent combined treatment with STTA and PDT,
      and 66 eyes underwent PDT alone. Time to vision loss, defined as a change of 0.3
      or more logarithm of minimum angle of resolution (logMAR) units, and time to
      retreatment were evaluated using the Kaplan-Meier survival analyses. Cox
      regression models were used to estimate the hazard ratios for those end points to
      investigate clinical risk characteristics. RESULTS: Patients who underwent
      combined STTA with PDT had a significantly lower risk of retreatment than did
      those who underwent PDT alone (hazard ratio, 0.59; 95% confidence interval, 0.36
      0.99). This beneficial association was found only in patients without polypoidal
      choroidal vasculopathy (PCV) lesions. However, combined treatment with STTA and
      PDT had no beneficial effect in reducing visual loss when compared with treatment
      with PDT alone. CONCLUSION: Combined treatment with STTA and PDT had a beneficial
      effect in reducing retreatment of AMD in Japanese patients. Those who had PCV
      lesions did not benefit from this additional treatment.

PMID- 19847609
TI  - Intraocular pressure elevation following triamcinolone acetonide administration
      as related to administration routes.
AB  - PURPOSE: To evaluate the incidence and risk factors of intraocular pressure (IOP)
      elevation following triamcinolone acetonide (TA) administration. METHODS: In this
      retrospective observational case series, patients (224 eyes of 202 patients) with
      diffuse diabetic macular edema (66 eyes), branch retinal vein occlusion (39
      eyes), central retinal vein occlusion (25 eyes), exudative age-related macular
      degeneration (49 eyes), myopic choroidal neovascularization (10 eyes), uveitis
      (30 eyes), or other conditions (5 eyes) were administered an intravitreal or
      posterior sub-Tenon capsule injection, or both, of TA. Sub-Tenon capsule
      injection was performed on 106 eyes (STTA group). Intravitreal injection was
      performed on 118 eyes (IVTA group), of which 85 eyes underwent simultaneous
      intravitreal and sub-Tenon capsule injections. Mean follow-up after TA
      administration was 15.9 +/- 10.4 (range, 3-39) months. The sub-Tenon capsule
      injection and intravitreal injection of TA were compared with respect to the
      frequency of IOP elevation and the time between TA administration and the initial
      IOP elevation, and the possible risk factors responsible for IOP elevation were
      identified. RESULTS: There was no significant difference in frequency of IOP > 21
      mmHg between the STTA group and the IVTA group (P = 0.0588). There was, however,
      a significant difference in the frequency of IOP > 30 mmHg between the two groups
      (P = 0.0004). In the IVTA group, more patients needed antiglaucoma medication
      than in the STTA group (P = 0.0052). The incidence rate of IOP elevation within 1
      week after TA administration in the IVTA group was significantly higher than in
      the STTA group (P = 0.0154). Risk factors for IOP elevation included higher
      baseline IOP (P < 0.0001), younger patients (P = 0.0095), and simultaneous
      administration of sub-Tenon capsule and intravitreal injections (P = 0.0228).
      CONCLUSIONS: Careful follow-up of IOP is required after TA injections.

PMID- 19847610
TI  - Endothelial damage of a donor cornea depending on the donor insertion method
      during Descemet-stripping automated endothelial keratoplasty in porcine eyes.
AB  - PURPOSE: To compare endothelial damage of the donor cornea in relation to the
      method of inserting the donor cornea into the recipient anterior chamber during
      Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: Fifteen
      enucleated pig eyes were used. The donor corneoscleral buttons were mounted in an
      artificial anterior chamber. The anterior lamella was excised using a
      microkeratome and punched using a trephine. The following methods were employed
      to insert the donor cornea into the recipient anterior chamber: (1) The donor was
      folded over, grasped using forceps, and inserted ("taco" technique). (2) The
      forceps were inserted and the edge of the donor was grasped and dragged into the
      chamber. (3) A loop was made at the edge of the donor by suturing with nylon. A
      hook was inserted to drag the donor by the loop into the chamber. After
      insertion, the incision on the recipient eye was extended, and the donor cornea
      was removed for examination. After vital staining, the samples were examined
      under a light microscope and a scanning electron microscope. RESULTS: With the
      taco technique, endothelial damage (17.9%) was observed in areas where the
      forceps held the donor. In the drag technique using forceps, endothelial damage
      (17.3%) was observed where the forceps made contact and in the folds in this
      area. In the drag technique using a suture, endothelial damage (18.8%) was
      observed in the area of the needle puncture and in folds in this area.
      CONCLUSION: The amount of endothelial damage did not differ significantly among
      the three different methods of donor insertion during DSAEK in this animal model,
      but each method exhibited a different endothelial damage pattern.

PMID- 19847611
TI  - Effect of 5-S-GAD on UV-B-induced cataracts in rats.
AB  - PURPOSE: 5-S-Glutathionyl-N-beta-alanyl-3,4-dihydroxyphenylalanine (5-S-GAD) is a
      novel antibacterial substance purified from Sarcophaga peregrina (flesh fly) that
      has both a radical scavenging activity and antioxidative activity. This is a
      report of an investigation of the effect of 5-S-GAD (eyedrops) on UVB-induced
      cataracts in rats. METHODS: Brown Norway male rats (n = 32; 7 weeks old) were
      treated with either 5-S-GAD 0.1%, 5-SGAD 1%, astaxanthin (AST) 0.1% suspension
      eyedrops or the vehicle alone (the solution without 5-S-GAD) three times a day
      (three doses at 5-min intervals each time). The treatment was scheduled 2 days
      before UV-B exposure and 2 days after UV-B exposure. Exposure to 100-200 mJ/cm(2)
      UV-B was performed once a week between drug treatments for 9 consecutive weeks,
      with a total dose of 1200 mJ/cm(2) UV-B. Ocular penetration of 5-S-GAD was
      analyzed using high-pressure liquid chromatography (HPLC). Cataract formation was
      documented by an anterior eye segment analysis system once a week under
      mydriasis. The light-scattering intensity (LSI) of the anterior superficial
      cortex region was measured. RESULTS: In the eighth to ninth week after the start
      of UV-B exposure, the LSI of anterior subcapsular lenses of 5-S-GAD-treated
      groups, as detected by HPLC, was significantly lower (P < 0.05) than that of the
      control, whereas no such difference was found in the AST-treated group.
      CONCLUSION: 5-S-GAD eyedrop application may delay the progression of UV-B-induced
      cataract in rats.

PMID- 19847612
TI  - Temperature-dependent ultrastructural changes in the cone interphotoreceptor
      matrix.
AB  - PURPOSE: To determine the temperature-dependent ultrastructural changes of the
      cone matrix sheath, a possible critical factor in the adhesive strength binding
      photoreceptors and pigment epithelial cells. METHODS: Aqueous-insoluble
      interphotoreceptor matrix (IPM) was extracted by soaking fresh bovine retinas in
      acidic HEPES-buffered solution followed by treatment with 1% Triton X-100 to
      remove cone membrane fragments. The IPM preparations were then incubated in the
      same buffer solution at either 34 degrees C, 37 degrees C, or 40 degrees C for 60
      min. After labeling with peanut agglutinin, the samples were prepared for
      electron microscopy. RESULTS: The cone matrix sheath, specifically stained with
      peanut agglutinin, was markedly condensed at 34 degrees C. It became more
      dispersed and composed of granular elements at 37 degrees C. At 40 degrees C, the
      matrix appeared as a network of fine filamentous structures. CONCLUSIONS: These
      findings suggest changing temperatures can alter the molecular organization of
      the IPM and thus influence its retinal adhesion.

PMID- 19847613
TI  - A case of oculodentodigital dysplasia syndrome with novel GJA1 gene mutation.
AB  - PURPOSE: To report a case of oculodentodigital dysplasia syndrome (ODDD) with a
      heterozygous mutation in GJA1 (connexin 43) gene. METHODS: A 9-year-old girl
      visited our hospital complaining of visual disturbances. The patient had
      microphthalmia, a small nose with hypoplastic alae nasi, and syndactyly. Visual
      acuity with prescribed glasses improved to 0.5 (1.2) OU 2 months after the first
      visit. She was satisfied with the new glasses and the improvement in visual
      acuity. Genomic DNA was extracted from leukocytes of the patient's peripheral
      blood in accordance with standard procedures, after obtaining parental informed
      consent. We amplified GJA1 exon 2 from her genomic DNA by the PCR method, and
      sequenced the product using the dye terminator method. RESULTS: S5C (c. 13A > T),
      a novel mutation in exon 2 of GJA1, was found in the patient. The parents had no
      mutation of GJAI, nor was there any sign of abnormality in other family members.
      No similar mutation could be found in the 50 genotyped normal subjects in the
      control group. CONCLUSIONS: A novel GJA1 mutation was detected in a Japanese ODDD
      patient. Glaucoma complications associated with ODDD have already been reported.
      Careful long-term monitoring and treatment are also necessary.

PMID- 19847614
TI  - A case of nodular fasciitis in the upper eyelid.

PMID- 19847615
TI  - Two cases of varicella zoster virus keratitis with atypical extensive
      pseudodendrites.

PMID- 19847616
TI  - Current characteristics of infectious keratitis at a tertiary referral center in
      South Korea.

PMID- 19847617
TI  - A case of necrotizing sclerokeratitis and endophthalmitis caused by Beauveria
      bassiana.

PMID- 19847618
TI  - Late appearance of an intracameral ophthalmic ointment globule after uneventful
      phacoemulsification.

PMID- 19847619
TI  - Bilateral multifocal retinal pigment epithelial detachments associated with
      abnormal multifocal electroretinograms.

PMID- 19847620
TI  - Predominant loss of rod-mediated electroretinogram response in a case of acute
      annular outer retinopathy.

PMID- 19847621
TI  - Bilateral optic disc macroaneurysm associated with acquired vascular loop.

PMID- 19847623
TI  - The invasiveness of five medulloblastoma cell lines in collagen gels.
AB  - Local recurrence continues to limit survival in medulloblastoma patients, largely
      related to the persistence of invasive cells at the site of tumour resection and
      leptomeningeal dissemination. Given the relative dearth of understanding of
      causative mechanisms behind the invasiveness of medulloblastomas, and a general
      lack of validated in vitro models with which to study them, our objectives were
      (1) to obtain quantitative data on the invasiveness of five distinct
      medulloblastoma cell lines within a 3-dimensional in vitro collagen-based model;
      and (2) to characterize some of the mechanisms behind invasion, specifically
      striving to identify proteolytic processes that occur as medulloblastoma cells
      disrupt and thereby invade the normal tissue surrounding them, and specific
      inhibitors of these proteolytic enzymes. Five different medulloblastoma cell
      lines (UW228-1, 2 and 3; Daoy, and Madsen) were implanted onto a 3-dimensional,
      type I collagen gel assay to assess tumour invasion distance and mean doubling
      time over 5 days. Proteolytic activity was assessed against collagen types I and
      IV by measuring the degradation of 3H-collagen I and IV to products soluble in
      100% w/v trichloroacetic acid; and general (neutral) proteolytic activity
      evaluated by measuring the degradation of 3H-albumin. In other experiments, cells
      were pre-exposed to a variety of protease inhibitors, including inhibitors of
      metalloproteinases and cysteine, serine and aspartic proteases, and then plated
      to identify any inhibition of invasion. Inter-group differences in mean invasion
      distance were assessed by means of Student's t-tests for non-paired subjects,
      with P < 0.05 set as the threshold for statistical significance. For the
      inhibitor studies, an inhibition index, called the inhibitory concentration 50,
      IC-50, was calculated by performing a regression analysis for each inhibitor
      tested over a range of concentrations, for each cell line. Within hours of
      implantation, individual cells readily detached from the surface of the cell
      aggregates and invaded the collagen matrix, to distances of up to 1,200 mum and
      at rates of up to 300-mum per day; the UW228-1 cell line clearly was less
      invasive than the other four cell lines. Proteolytic activity was identified
      against collagen type I, but not against collagen type IV or albumin; but there
      was no apparent correlation between invasion distance and either cell doubling
      time or the amount of collagen type I proteolytic activity. Both
      metalloproteinase inhibitors suppressed tumour invasion, as did one of two
      cysteine protease inhibitors; but there was no tumour suppression with either
      serine or aspartic protease inhibition. MMP-1 and 2, and TIMP-1 and 2 all were
      detectable by Western blot analysis. Medulloblastoma cell invasiveness within the
      3-dimensional model used here appears to depend upon a combination of
      metalloproteinase and cysteine protease activity, a finding that may suggest
      areas for potential future clinical investigation and therapy.

PMID- 19847624
TI  - Hospital-based costs associated with venous thromboembolism prophylaxis regimens.
AB  - Clinically and economically, venous thromboembolic (VTE) disease represents a
      significant burden to the US healthcare system. This analysis compares the total
      direct medical costs associated with VTE prophylaxis with enoxaparin and
      unfractionated heparin (UFH). Hospital discharge and billing records were
      extracted from the Premier Perspective database (January 2002-December 2006). The
      primary outcome was the total direct medical costs for discharges that were at
      risk of VTE and received enoxaparin or UFH. A total of 894,364 discharge records
      met the study inclusion criteria, of which 39.4% received enoxaparin and 60.6%
      received UFH. After adjustment for pre-defined covariates, mean total direct
      medical costs per discharge for the UFH group were $6,443, $1,080 more than those
      for the enoxaparin group ($5,363; P < .0001). In conclusion, enoxaparin
      prophylaxis is a cost-saving therapy, when compared with UFH, for the prevention
      of VTE in patients with a diverse range of medical conditions conferring VTE
      risk.

PMID- 19847625
TI  - Heat denatured/aggregated albumin-based biomaterial: effects  of preparation
      parameters on biodegradability and mechanical  properties.
AB  - Albumin-based biomaterials prepared using heat-aggregation or cross-linking
      agents have been used in various biomedical applications such as solder materials
      for laser-assisted tissue welding, anti-bacterial coatings and drug carriers. In
      this study, solid albumin-based materials were prepared via heat aggregation of
      albumin solution. The study aimed to determine the influences of the preparation
      parameters such as albumin concentration in solution, solution pH and
      temperature, on the mechanical properties as well as the biodegradation rate of
      heat-aggregated albumin-based materials. The results demonstrated that the
      materials prepared from the albumin solution with the pH of 8.5 had the highest
      mechanical strength. Augmenting the albumin concentration in solution led to an
      increase in mechanical strength, and the materials prepared from the solution
      with isoelectric albumin pH (pH 4.8) possessed the lowest biodegradation rate and
      those prepared at pH 12 showed the highest biodegradation rate.

PMID- 19847626
TI  - Inhalable antibiotic delivery using a dry powder co-delivering recombinant
      deoxyribonuclease and ciprofloxacin for treatment of cystic fibrosis.
AB  - PURPOSE: To achieve efficient antibiotic delivery to the cystic fibrosis (CF)
      airway using a single inhalable powder co-encapsulating a mucolytic and an
      antibiotic. METHODS: Inhalable dry powders containing deoxyribonuclease and/or
      ciprofloxacin (DNase, Cipro, and DNase/Cipro powders) were produced by spray
      drying with dipalmitylphosphatidylcholine, albumin, and lactose as excipients,
      and their antibacterial effects were evaluated using the artificial sputum model.
      RESULTS: All powders showed mass median aerodynamic diameters below 5 microm.
      Both drugs were loaded in the dry powders without loss in quantity and activity.
      Dry powders containing DNase significantly decreased the storage modulus of the
      artificial sputum medium in less than 30 min. When applied to artificial sputum
      laden with Pseudomonas aeruginosa, Cipro/DNase powder showed better antibacterial
      activity than Cipro powder. The higher activity of the Cipro/DNase powder is
      attributable to the mucolytic activity of DNase, which promotes penetration of
      the dry powder into the artificial sputum and efficient dissolution and diffusion
      of ciprofloxacin. CONCLUSIONS: Inhalational delivery of antibiotics to the CF
      airway can be optimized when the sputum barrier is concomitantly addressed. Co
      delivery of antibiotics and DNase using an inhalable particle system may be a
      promising strategy for local antipseudomonal therapy in the CF airway.

PMID- 19847627
TI  - Physiologically-based PK/PD modelling of therapeutic macromolecules.
AB  - Therapeutic proteins are a diverse class of drugs consisting of naturally
      occurring or modified proteins, and due to their size and physico-chemical
      properties, they can pose challenges for the pharmacokinetic and pharmacodynamic
      studies. Physiologically-based pharmacokinetics (PBPK) modelling has been
      effective for early in silico prediction of pharmacokinetic properties of new
      drugs. The aim of the present workshop was to discuss the feasibility of PBPK
      modelling of macromolecules. The classical PBPK approach was discussed with a
      presentation of the successful example of PBPK modelling of cyclosporine A. PBPK
      model was performed with transport of the cyclosporine across cell membranes,
      affinity to plasma proteins and active membrane transporters included to describe
      drug transport between physiological compartments. For macromolecules, complex
      PBPK modelling or permeability-limited and/or target-mediated distribution was
      discussed. It was generally agreed that PBPK modelling was feasible and
      desirable. The role of the lymphatic system should be considered when absorption
      after extravascular administration is modelled. Target-mediated drug disposition
      was regarded as an important feature for generation of PK models. Complex PK
      models may not be necessary when a limited number of organs are affected. More
      mechanistic PK/PD models will be relevant when adverse events/toxicity are
      included in the PK/PD modelling.

PMID- 19847628
TI  - Assessing drug distribution in tissues expressing P-glycoprotein using
      physiologically based pharmacokinetic modeling: identification of important model
      parameters through global sensitivity analysis.
AB  - The structural complexity of a PBPK model is usually accompanied with significant
      uncertainty in estimating its input parameters. In the last decade, the global
      sensitivity analysis, which accounts for the variability of all model input
      parameters simultaneously as well as their correlations, has gained a wide
      attention as a powerful probing technique to identify and control biological
      model uncertainties. However, the current sensitivity analysis techniques used in
      PBPK modeling often neglect the correlation between these input parameters. We
      introduce a new strategy in the PBPK modeling field to investigate how the
      uncertainty and variability of correlated input parameters influence the outcomes
      of the drug distribution process based on a model we recently developed to
      explain and predict drug distribution in tissues expressing P-glycoprotein (P
      gp). As direct results, we will also identify the most important input parameters
      having the largest contribution to the variability and uncertainty of model
      outcomes. We combined multivariate random sampling with a ranking procedure.
      Monte-Carlo simulations were performed on the PBPK model with eighteen model
      input parameters. Log-normal distributions were assumed for these parameters
      according to literature and their reported correlations were also included. A
      multivariate sensitivity analysis was then performed to identify the input
      parameters with the greatest influence on model predictions. The partial rank
      correlation coefficients (PRCC) were calculated to establish the input-output
      relationships. A moderate variability of predicted C(last) and C(max) was
      observed in liver, heart and brain tissues in the presence or absence of P-gp
      activity. The major statistical difference in model outcomes of the predicted
      median values has been obtained in brain tissue. PRCC calculation confirmed the
      importance for a better quantitative characterisation of input parameters related
      to the passive diffusion and active transport of the unbound drug through the
      blood-tissue membrane in heart and brain. This approach has also identified as
      important input parameters those related to the drug metabolism for the
      prediction of model outcomes in liver and plasma. The proposed Monte-Carlo/PRCC
      approach was aimed to address the effect of input parameters correlation in a
      PBPK model. It allowed the identification of important input parameters that
      require additional attention in research for strengthening the physiological
      knowledge of drug distribution in mammalian tissues expressing P-gp, thereby
      reducing the uncertainty of model predictions.

PMID- 19847629
TI  - Non-compartmental estimation of pharmacokinetic parameters in serial sampling
      designs.
AB  - Pharmacokinetic studies are commonly analyzed using a two-stage approach where
      the first stage involves estimation of pharmacokinetic parameters for each
      subject separately and the second stage uses the individual parameter estimates
      for statistical inference. This two-stage approach is not applicable in sparse
      sampling situations where only one sample is available per subject. Nonlinear
      models are often applied to analyze pharmacokinetic data assessed in such serial
      sampling designs. Modelling approaches are suitable provided that the form of the
      true model is known, which is rarely the case in early stages of drug
      development. This paper presents an alternative approach to estimate
      pharmacokinetic parameters based on non-compartmental and asymptotic theories in
      the case of serial sampling when a drug is given as an intravenous bolus. The
      statistical properties of estimators of the pharmacokinetic parameters are
      investigated and evaluated using Monte Carlo simulations.

PMID- 19847630
TI  - Satisfaction with dental case management among people living with HIV/AIDS.
AB  - We evaluated access to and satisfaction with dental services for people living
      with HIV/AIDS receiving services from a dental case manager (DCM). People living
      with HIV/AIDS who had received dental services at two Community Dental Centers on
      Cape Cod, Massachusetts were eligible to participate in a mailed, anonymous
      return, Dental Satisfaction Survey (N = 160). Overall, respondents were satisfied
      with the dental care they had received. Most patients (58%) were new to the
      practice and were more likely to report that they had not been seen by a dental
      provider for more than 12 months (OR 3.0, P = 0.044). The majority of respondents
      reported that they heard about the clinic from local agencies. Of respondents
      recognizing they had a DCM, almost all answered that their DCM had helped them
      receive the care they needed. Respondents who agreed that they sometimes avoided
      going to the dentist due to pain were significantly more likely to report that
      they had a dental case manager than patients who disagreed (OR 3.42, P = 0.027).
      When patients were asked how their DCM had helped them, themes identified
      included: assisting with access to dental care, conducting a needs assessment,
      and providing comfort. People living with HIV/AIDS often have unmet needs
      regarding dental care. The addition of the DCM to the dental facility appears to
      facilitate access to dental care for those connected to medical care through
      community outreach/partnerships and provides some respondents with an identified
      dental advocate.

PMID- 19847631
TI  - Minding the immunization gap: family characteristics associated with completion
      rates in rural Ethiopia.
AB  - To examine risk factors for lack of immunization, we tested the impact of
      maternal, paternal, and household variables on child immunization status in
      children >or =1 year in a rural area of Ethiopia. Data collected by face-to-face
      interview on maternal, paternal, household and child variables from cross
      sectional random sample community-based study on health and well-being in rural
      Ethiopia was used to test hypotheses on immunization status of children (n =
      924). Bivariate and multivariate logistic regression models were used for two
      immunization outcomes: record of at least one vaccination, and record of DPT3,
      indicating completion of the DPT series. Complete data were available for 924
      children > or =1 year of which 79% had at least one vaccination. Of those, 64%
      had DPT3/Polio3; below recommended coverage level. Children were more likely to
      be vaccinated if the mother reported antenatal care (ANC), and less likely to be
      vaccinated if the mother had a history of stillbirth, and no opinion of health
      center. Children were more likely to have DPT3 if: mother had > or =1 year of
      education, mother reported ANC, or older paternal age. Children were less likely
      to have DPT3 in households with food insecurity and no maternal opinion of health
      center. The study had three findings with implications for immunization
      programming: (1) Mothers completing the recommended ANC visits is strongly
      associated with receiving at least one vaccination and with completing a
      vaccination series; (2) Maternal education is associated with a completed
      vaccination series; (3) Paternal characteristics may affect vaccination series
      completion.

PMID- 19847634
TI  - Morbidity and mortality risk among the "forgotten few": why are girls in the
      justice system in such poor health?
AB  - The present study assessed the physical health of a population of girls sentenced
      to custody in a large US State via medical examinations and clinical assessments
      in adolescence and young adulthood. Findings indicated that injuries, obesity,
      and sexually transmitted diseases were the norm, with over 50% of the population
      meeting criteria for each of these health problems. A dose-response relationship
      was documented between childhood victimization and injuries and injury risk in
      adolescence and self-harm, HIV risk, physical health symptoms, and
      hospitalizations in young adulthood. The relationship between childhood
      victimization and poor adult physical health was fully mediated by health-risk
      behaviors in adolescence. Clinical and policy implications of the high mortality
      and morbidity risk among female juvenile offenders are discussed.

PMID- 19847633
TI  - Purification and mass spectrometric characterization of Sesbania aculeata
      (Dhaincha) stem lectin.
AB  - A glucose specific lectin (STA) was isolated from Sesbania aculeata stem by using
      Sephadex G-50 affinity column chromatography. The lectin is a glycoprotein having
      29 kDa subunit molecular weight. Two dimensional gel electrophoresis analysis
      revealed that the lectin existed in two isomeric forms with varied carbohydrate
      content as analyzed by high performance anion exchange chromatography-pulsed
      amperometric detector (HPAEC-PAD). Matrix-assisted laser desorption ionization
      time of flight (MALDI-TOF) and N-terminal sequence (LDSLSFTYNNFE) analysis of
      this lectin showed 95% homology with stem lectin SL-I (accession no. AJ585523)
      from peanut plant. The nucleotide sequence of the lectin (STA) was submitted to
      the gene bank (accession no. EU263636).

PMID- 19847636
TI  - Reactions to self-sampling for ano-rectal sexually transmitted infections among
      men who have sex with men: a qualitative study.
AB  - Little is known about men's potential motivations and barriers associated with
      specific sexually transmitted infections (STI) testing methods. In this study, we
      examined experiences of self-sampling for ano-rectal STI among men who have sex
      with men (MSM) in a midwestern community in the U.S. A total of 75 MSM were
      recruited from community venues throughout Indianapolis, Indiana. Participants
      completed semi-structured interviews, were asked to obtain ano-rectal self-sample
      in a private restroom, and were asked open-ended questions about their
      experiences with ano-rectal self-sampling for STI. Participants included 35
      White, 27 Black, and 13 Latino MSM who ranged in age from 18 to 57 years.
      Regardless of sexual practices, most participants who obtained an ano-rectal self
      sample (68/75) reported that the sampling procedure was relatively painless and
      physically easy. However, regardless of previous receptive anal sex, participants
      also expressed concerns about the nature of the test (i.e., inserting something
      into their rectum), which required increased levels of privacy and cleanliness
      compared to collection of urine samples. Self-sampling proved to be a feasible
      and acceptable method of collecting ano-rectal STI specimens among MSM. Increased
      testing for ano-rectal STI among MSM may require addressing the location of
      sampling and testing sites, existing negative perceptions of ano-rectal self
      sampling, and the measures in place to promote privacy and cleanliness.

PMID- 19847635
TI  - Alternative time representation in dopamine models.
AB  - Dopaminergic neuron activity has been modeled during learning and appetitive
      behavior, most commonly using the temporal-difference (TD) algorithm. However, a
      proper representation of elapsed time and of the exact task is usually required
      for the model to work. Most models use timing elements such as delay-line
      representations of time that are not biologically realistic for intervals in the
      range of seconds. The interval-timing literature provides several alternatives.
      One of them is that timing could emerge from general network dynamics, instead of
      coming from a dedicated circuit. Here, we present a general rate-based learning
      model based on long short-term memory (LSTM) networks that learns a time
      representation when needed. Using a naive network learning its environment in
      conjunction with TD, we reproduce dopamine activity in appetitive trace
      conditioning with a constant CS-US interval, including probe trials with
      unexpected delays. The proposed model learns a representation of the environment
      dynamics in an adaptive biologically plausible framework, without recourse to
      delay lines or other special-purpose circuits. Instead, the model predicts that
      the task-dependent representation of time is learned by experience, is encoded in
      ramp-like changes in single-neuron activity distributed across small neural
      networks, and reflects a temporal integration mechanism resulting from the
      inherent dynamics of recurrent loops within the network. The model also
      reproduces the known finding that trace conditioning is more difficult than delay
      conditioning and that the learned representation of the task can be highly
      dependent on the types of trials experienced during training. Finally, it
      suggests that the phasic dopaminergic signal could facilitate learning in the
      cortex.

PMID- 19847638
TI  - Risk of reincarceration among prisoners with co-occurring severe mental illness
      and substance use disorders.
AB  - This study examined whether the presence of a comorbid substance use disorder
      increased the risk of criminal recidivism and reincarceration in prison inmates
      with a severe mental illness. Our analyses of more than 61,000 Texas prison
      inmates showed that those with a co-occurring psychiatric and substance use
      disorder exhibited a substantially higher risk of multiple incarcerations over a
      6-year period compared to inmates with psychiatric disorders alone or substance
      use disorders alone. Further research is needed to identify the factors
      associated with criminal recidivism among released prisoners with co-occurring
      disorders.

PMID- 19847637
TI  - Acculturation, coping styles, and health risk behaviors among HIV positive
      Latinas.
AB  - This study examined the relationships among acculturation, coping styles,
      substance use, sexual risk behavior, and medication non-adherence among 219
      Latinas living with HIV/AIDS in Los Angeles, CA. Coping styles were hypothesized
      to mediate the link between acculturation and health risk behaviors for HIV
      positive Latinas. Structural equation modeling revealed that greater
      acculturation was related to less positive coping and more negative coping. In
      turn, negative coping was associated with more health risk behaviors and more non
      adherence. Positive coping was associated with less substance use as reflected in
      use of cigarettes and alcohol and less non-adherence. Coping styles mediated the
      relationship between acculturation and health risk behaviors. Findings echo
      previous works examining the Hispanic Health Paradox wherein more acculturated
      Latinos exhibit increased risk behavior and maladaptive coping styles. HIV/AIDS
      interventions need to be mindful of cultural differences within Hispanic
      populations and be tailored to address these differences.

PMID- 19847639
TI  - Quantitative decision-making in preimplantation genetic (aneuploidy) screening
      (PGS).
AB  - PURPOSE: To analyze using hypergeometric probability statistics the impact of
      performing preimplantation genetic screening (PGS) on a cohort of day 3 cleavage
      stage embryos. METHODS: Statistical mathematical modeling. RESULTS: We find the
      benefit of performing PGS is highly dependent on the number of day 3 embryos
      available for biopsy. Additional hidden variables that determine the outcome of
      PGS are the rates of aneuploidy and mosaicism, and the probability of a
      chromosomally mosaic embryo to test "normal". If PGS is performed, our analysis
      shows that many combinations of the number of biopsiable embryos, and the rates
      of aneuploidy and mosaicism results in a marginal benefit from the intervention.
      Other combinations are detrimental if PGS is actually undertaken. Finally,
      increases in PGS error rates lead to a rapid loss in the ability of PGS to
      provide useful discriminatory information. CONCLUSION: We set out the statistical
      framework to determine the limits of PGS when a specific number of day 3
      preimplantation embryos are available for biopsy. In general, PGS cannot be
      recommended a priori for a specific clinical situation due to the statistical
      uncertainties associated with the different hidden variable quantitative
      parameters considered important to the clinical outcome.

PMID- 19847640
TI  - In vitro fertilisation (IVF) with donor eggs in post-menopausal women: are there
      differences in pregnancy outcomes in women with premature ovarian failure (POF)
      compared with women with physiological age-related menopause?
AB  - PURPOSE: This study assessed pregnancy rates and obstetric outcomes in women with
      premature ovarian failure (Group A) with post-menopausal women > or =40 years
      (Group B) who had IVF +/- ICSI using donor eggs. METHODS: This was a
      retrospective analysis of 54 recipients with either premature ovarian failure or
      physiological menopause undergoing oocyte donation between 2000 and 2007 at
      Monash IVF. RESULTS: The average number of stimulated cycles required for a woman
      in group A and B to deliver a baby was 1.75 and 1.4 respectively. Both groups had
      high cumulative pregnancy rates; however, there was a statistically significant
      difference with regards to rates of complications. CONCLUSION: Oocyte donation in
      both premature ovarian failure and physiological menopause is highly successful
      and cumulative pregnancy rate is an important statistic which can be used to
      inform women seeking this technique. High rates of complications, in conjunction
      with individual risk-factor analysis needs to be considered when counselling post
      menopausal women about oocyte donation.

PMID- 19847641
TI  - Evaluating the interplay between spirituality, personality and stress.
AB  - Spirituality and the big five personality traits may be risk or protective
      factors for coping with stress. We hypothesized young adults who reported higher
      spirituality ratings would demonstrate lower sympathetic nervous system arousal
      and better emotional coping when exposed to a laboratory stressor compared to
      those who rated themselves lower in spirituality. We also compared spirituality
      groups on trait anger, neuroticism, conscientiousness, extraversion,
      agreeableness and openness to experience. Eighty participants completed trait
      state anger, personality and spirituality questionnaires and were grouped into
      low, average and high spirituality. Participants' physiological responses were
      monitored before and during a stressful event. Significant differences were found
      between low, average and high spirituality groups' respiration rate and emotional
      response to the stressor. Significant differences were also found between
      spirituality groups in extraversion, agreeableness, conscientiousness, trait
      anger and neuroticism. Females reported higher levels of spirituality and
      conscientiousness than males.

PMID- 19847642
TI  - Alcohol consumption and breast tumor mitochondrial DNA mutations.
AB  - Mitochondrial DNA (mtDNA) mutations are frequent in breast tumors, but the
      etiology of these mutations is unknown. We hypothesized that these mutations are
      associated with exposures that affect oxidative stress such as alcohol
      metabolism. Using archived tumor blocks from incident breast cancer cases in a
      case control study, the Western New York Exposures and Breast Cancer (WEB) study,
      analysis of mtDNA mutations was conducted on 128 breast cancer cases selected
      based on extremes of alcohol intake. Temporal temperature gradient gel
      electrophoresis (TTGE) was used to screen the entire mtDNA genome and sequencing
      was completed for all TTGE positive samples. Case-case comparisons were completed
      using unconditional logistic regression to determine the relative prevalence of
      the mutations by exposures including alcohol consumption, manganese superoxide
      dismutase (MnSOD) genotype, nutrient intake related to oxidative stress and
      established breast cancer risk factors. Somatic mtDNA mutations were found in 60
      of the 128 tumors examined. There were no differences in the prevalence of mtDNA
      mutations by alcohol consumption, MnSOD genotype or dietary intake. The
      likelihood of mtDNA mutations was reduced among those with a positive family
      history for breast cancer (OR = 0.33, CI = 0.12-0.92), among postmenopausal women
      who used hormone replacement therapy (OR = 0.46, CI = 0.19-1.08, P = 0.08) and
      was increased for ER negative tumors (OR = 2.05, CI = 0.95-4.43, P = 0.07).
      Consistent with previous studies, we found that mtDNA mutations are a frequent
      occurrence in breast tumors. An understanding of the etiology of mtDNA mutations
      may provide insight into breast carcinogenesis.

PMID- 19847643
TI  - Coffee and tea intake and risk of breast cancer.
AB  - Known risk factors account for about 10-15% of breast cancer incidence suggesting
      that lifestyle exposures are crucial in its etiology. Previous epidemiological
      studies on the association between coffee and tea consumption and breast cancer
      risk have been inconsistent. We investigated the association of coffee and tea
      consumption with the risk of breast cancer among women in EPIC-NL cohort, a
      population-based prospective cohort in Netherlands with 27,323 participants.
      Exposure was measured by a validated food frequency questionnaire, and the
      outcome was verified by direct linkage with the Netherlands Cancer Registry. A
      total of 681 invasive primary breast cancers were diagnosed in 9.6 years of
      follow-up. Coffee intake increased the risk of breast cancer by more than twofold
      as compared to non-consumers (HR; 2.25, 95% CI; 1.30-3.90). This association did
      not hold after multivariate adjustment which resulted in a HR of 1.17, 95% CI;
      0.65-2.12. After adjustment to breast cancer risk factors and lifestyle, no
      association was observed between intake of coffee or tea and risk of breast
      cancer across all categories of intake. These results were also not altered by
      body mass index (BMI). Coffee and tea consumption does not seem to be related to
      the risk of breast cancer in women.

PMID- 19847644
TI  - Menin, a product of the MENI gene, binds to estrogen receptor to enhance its
      activity in breast cancer cells: possibility of a novel predictive factor for
      tamoxifen resistance.
AB  - Multiple coactivator and corepressor complexes play an important role in
      endocrine processes and breast cancer; in particular, estrogen and estrogen
      receptor-alpha (ERalpha) promote the proliferation of breast cancer cells. Menin
      is a tumor suppressor encoded by Men1 that is mutated in the human-inherited
      tumor syndrome multiple endocrine neoplasia type 1 (MEN1); it also serves as a
      critical link in the recruitment of nuclear receptor-mediated transcription.
      Here, we show that menin expressed in breast cancer cell line MCF-7 is
      colocalized with ERalpha and functions as a direct coactivator of ER-mediated
      transcription in breast cancer cells. In MCF-7 cells, coexpression of menin and
      estrogen-response element-luciferase induced the activity of the latter in a
      hormone-dependent manner. Cells knocked down for ERalpha exhibited impaired ERE
      luciferase activity induced by menin. Mammalian two-hybrid assay and GST pull
      down assays indicated that menin could interact with the AF-2 domain of ERalpha.
      These results indicate that menin is a direct activator of ERalpha function.
      Tamoxifen inhibited the binding of menin to AF-2 in mammalian two-hybrid assay,
      but in menin-overexpressing clones, tamoxifen suppressed ERE-luciferase activity
      only to the levels of nontreated wild-type MCF-7. In a clinical study with 65 ER
      positive breast cancer samples-all of which had been treated with tamoxifen for 2
      5 years as adjuvant therapies--menin-positive tumors had a worse outcome than
      menin-negative ones. These indicated that menin can function as a transcriptional
      regulator of ERalpha and is a possible predictive factor for tamoxifen
      resistance.

PMID- 19847645
TI  - Clinical problems in community mental health care for patients with severe
      borderline personality disorder.
AB  - The objective of this research was to assess the problems that professionals
      perceive in the community mental health care for patients with severe borderline
      personality disorder that do not fit into specialized therapy. A group of
      national experts (n = 8) participated in a four-phase Delphi-procedure to
      identify and prioritize the problems. A total of 36 problems reflecting five
      categories was found: patient-related, professional-related, interaction-related,
      social system-related, and mental health care-related. Problems with attachment
      and dependency and social issues were important patient problems while a lack of
      skills was an important professional problem. Support from the patient's social
      system and the mental health system were identified as limited, which resulted in
      both the patient and the professional feeling isolated. Patient, professional,
      and organisational characteristics of community care differ substantially from
      those of specialized care. The field is thus in need of a more tailored approach
      that takes these differences into account.

PMID- 19847646
TI  - Treatment outcome in patients receiving assertive community treatment.
AB  - In an observational study of severely mentally ill patients treated in assertive
      community treatment (ACT) teams, we investigated how treatment outcome was
      associated with demographic factors, clinical factors, and motivation for
      treatment. To determine psychosocial outcome, patients were routinely assessed
      using the Health of the Nation Outcome Scales (HoNOS). Trends over time were
      analyzed using a mixed model with repeated measures. The HoNOS total score was
      modeled as a function of treatment duration and patient-dependent covariates.
      Data comprised 637 assessments of 139 patients; mean duration of follow-up was
      27.4 months (SD = 5.4). Substance abuse, higher age, problems with motivation,
      and lower educational level were associated with higher HoNOS total scores (i.e.,
      worse outcome). To improve treatment outcome, we recommend better implementation
      of ACT, and also the implementation of additional programs targeting subgroups
      which seem to benefit less from ACT.

PMID- 19847647
TI  - Parents' conceptualization of adolescents' mental health problems: who adopts a
      psychiatric perspective and does it make a difference?
AB  - How parents give meaning to the problems of adolescents diagnosed with mental
      disorders and receiving treatment is likely related to important outcomes
      including parental well-being and commitment to treatment, as well as their own
      behaviors and reactions to their child. The aim of this cross-sectional, mixed
      method study of 70 parents of adolescents receiving wraparound mental health
      services is to examine: (1) how parents conceptualize their child's MH problems;
      (2) factors related to parents' conceptualization of youths' problems using
      medical model terms; and (3) associations between parents' problem
      conceptualization and their emotional or coping responses to their child having
      psychiatric problem(s). Content analysis indicated that 54.3% of parents
      definitively conceptualized adolescents' problems using psychiatric terms, 37.1%
      reported uncertainty about the nature of their child's problems, and 8.6% gave
      alternative, non-psychiatric explanations for their child's problems. We found
      significant relationships between parents' problem conceptualization and their
      attitudes and experience with MH treatment, demographics, as well as with
      adolescents' clinical characteristics. Parents who conceptualized problems using
      psychiatric terminology were more likely to express sadness and pessimism
      relative to other parents, though there were no differences in expressions of
      worry, guilt, pragmatism and optimism by problem conceptualization.

PMID- 19847648
TI  - University-community mental health center collaboration: encouraging the
      dissemination of empirically-based treatment and practice.
AB  - Community Mental Health Centers (CMHC) are valuable resources for urban youth and
      families across the nation. Community demands for high volumes of clinical
      service, however, often render these agencies without ability to fully evaluate
      provided services or conduct rigorous research with their target populations.
      This report asserts the importance of establishing effective collaborations
      between research-oriented universities and CMHCs in an effort to bridge the gap
      between empirically-based treatments and "real world" clinical practice.
      Furthermore, this report explains the establishment of a mutually informative and
      beneficial university-CMHC collaboration between the Disruptive Behavior Clinic
      at the University of Illinois-Chicago and the Community Mental Health Council
      (CMHC) on an evidence-based outpatient family therapy protocol for urban youth
      with behavior problems. Values and guidelines to facilitate evidence-based
      practice for fellow academic institutions are asserted. University-CMHC
      collaboration is an effective way to bring empirically-based practice to the
      "real world," front-line practice settings of community-based agencies that serve
      urban youth. Further research with regard to the maintenance and sustainability
      of these collaborations is suggested.

PMID- 19847649
TI  - The effects of a fat- and sugar-enriched diet and chronic stress on nonalcoholic
      fatty liver disease in male Wistar rats.
AB  - PURPOSE: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is still
      under debate. The aim of this study was to investigate the effects of a long-term
      fat- and sugar-enriched diet (FSED) and chronic stress (CS) on NAFLD. METHODS:
      Male Wistar rats were fed on either a standard diet or a FSED and given CS, a
      random electric foot shock (2 hr/morning and afternoon per day), or not for 12
      weeks. After the experimental period, epididymal adipose tissue weight, sign of
      visceral obesity (VO), and hepatic index (HI) were measured. At sacrifice blood
      samples and liver were obtained. Histology of the liver was blindly determined by
      a pathologist. RESULTS: Histopathologically, moderate to severe steatosis,
      ballooning hepatocytes, and portal or lobules inflammation were observed in the
      FSED+CS group. However, mild to moderate steatosis with a few portal inflammation
      in the FSED group and mild steatosis or not with a few portal inflammation in the
      CS group were found correspondingly. In addition, more severe blood-fat disorder,
      high HI, fatty metabolic dysfunction, oxidative stress, high expressions of C
      reactive protein mRNA and low expressions of peroxisome proliferator-activated
      receptor alpha mRNA in the liver were also revealed in the FSED+CS group. But,
      the degree of VO was not different between the FSED and FSED+CS groups.
      CONCLUSION: The observations strongly suggest that chronic stress can aggravate
      fat- and sugar-enriched diet-induced NAFLD from steatosis to steatohepatitis in
      male Wistar rats, although VO is not changed.

PMID- 19847650
TI  - Purified micronized flavonoid fraction ameliorates the injury of spleen and ileum
      secondary to hepatic ischemia-reperfusion in rats.
AB  - BACKGROUND: Flavonoids have been subjected to considerable investigations due to
      their antioxidant and anti-inflammatory properties. Yet the effects of flavonoids
      on the ileum and spleen against hepatic ischemia-reperfusion injury have so far
      not been addressed. AIMS: We aimed to investigate whether micronized purified
      flavonoid fraction (MPFF) protects the ileum and spleen against hepatic ischemia
      reperfusion injury. METHODS: Rats were subjected to hepatic ischemia by clamping
      the hilar area of the rats for 60 min, followed by 60 min of reperfusion. Rats in
      the treatment group were treated with MPFF (80 mg/kg/day) by gavage for 3 days
      before surgery, 30 min prior to ischemia and just before the reperfusion. After
      the reperfusion period, all rats were sacrificed. Ileal and splenic tissues were
      taken for histological evaluation and determination of the total antioxidant
      capacity (TAC), catalase, total oxidant status (TOS), oxidative stress index
      (OSI) and myeloperoxidase (MPO) levels. RESULTS: TAC levels in the splenic tissue
      and intestinal tissue were significantly higher in the treatment group than in
      the control group (P < 0.01 for both). TOS, OSI, and MPO in splenic tissue (P <
      0.01, P < 0.05, and P < 0.05, respectively) and intestinal tissue (P < 0.01, P <
      0.01, and P < 0.001, respectively) were significantly lower in the treatment
      group than in the control group. Histological tissue damage of intestinal tissue
      was milder in the treatment group than in the control group. CONCLUSION: The
      results of this study indicated that MPFF pretreatment significantly limited the
      injury to the small intestine and spleen induced by hepatic ischemia-reperfusion
      in rats.

PMID- 19847651
TI  - An integrated computational and experimental model of nitric oxide-red blood cell
      interactions.
AB  - In blood vessels, nitric oxide homeostasis is maintained by its formation by
      endothelial nitric oxide synthase and its consumption in smooth muscle cells and
      in vascular lumen by red blood cell (RBC) encapsulated hemoglobin (Hb). Free
      hemoglobin has a very high reaction rate (k(Hb-NO) approximately 10(7) M(-1) s(
      1)) with NO as compared to RBC-Hb. Mechanisms of reduced NO uptake by RBC-Hb has
      been extensively studied in recent years. A critical factor in the investigation
      of NO-RBC interactions is delivery of NO. Common NO delivery methods include use
      of NO donors and bolus saturated NO solutions, which delivers NO homogeneously
      and only in the vicinity of bolus, respectively. In this study, we developed a
      flow system that uses gaseous delivery of NO through a polymeric semi-permeable
      membrane to obtain precise and uniform NO concentrations for NO-RBC interactions.
      We conducted experiments using the flow system to study the effect of NO
      concentrations, hematocrit and RBC suspension flow rates on NO-RBC interactions.
      We developed a computational model to simulate NO transport and to estimate the
      reaction rate constant for NO-RBC interaction in the flow system. Our results
      showed that NO consumption of RBCs (i) increased linearly with an increase in
      available NO, and (ii) decreased with increase in RBCs suspension flow rate. We
      estimated the reaction rate constant for NO-RBC interactions to be 0.2 x 10(5) M(
      1) s(-1) which is approximately 1250-fold lower than NO consumption by free
      hemoglobin and approximately 2.5-20 fold slower than reported NO-RBC reaction
      rate.

PMID- 19847653
TI  - Hypopituitarism due to sports related head trauma and the effects of growth
      hormone replacement in retired amateur boxers.
AB  - Traumatic brain injury (TBI) has been recently recognized as a leading cause of
      pituitary dysfunction. Current data clearly demonstrated that sports related head
      trauma due to boxing, kickboxing, and soccer might results in pituitary hormone
      deficiencies, isolated growth hormone (GH) deficiency in particular. In the
      present report physiologic dose GH replacement therapy (GHRT) was performed in
      two GH deficient retired amateur boxers for the first time. The boxers received
      recombinant GH for 6 months. After 6 months of GHRT there were substantial
      improvements, but not complete normalization, in the body composition parameters,
      lipid profiles and quality of life scores in both boxers. These preliminary
      results suggest that GHRT may have beneficial effects in retired boxers with
      severe isolated GH deficiency due to sports related head trauma. But more data
      with higher number of boxers and longer GHRT duration are warranted.

PMID- 19847655
TI  - The mariner Mos1 transposase produced in tobacco is active in vitro.
AB  - The mariner-like transposon Mos1 is used for insertional mutagenesis and
      transgenesis in different animals (insects, nematodes), but has never been used
      in plants. In this paper, the transposition activity of Mos1 was tested in
      Nicotiana tabacum, but no transposition event was detected. In an attempt to
      understand the absence of in planta transposition, Mos1 transposase (MOS1) was
      produced and purified from transgenic tobacco (HMNtMOS1). HMNtMOS1 was able to
      perform all transposition reaction steps in vitro: binding to ITR, excision and
      integration of the same pseudo-transposon used in in planta transposition assays.
      The in vitro transposition reaction was not inhibited by tobacco nuclear
      proteins, and did not depend on the temperature used for plant growth. Several
      hypotheses are proposed that could explain the inhibition of HMNtMOS1 activity in
      planta.

PMID- 19847656
TI  - Does physical activity modify the risk of obesity for type 2 diabetes: a review
      of epidemiological data.
AB  - Obesity and physical inactivity are both risk factors for type 2 diabetes. Since
      they are strongly associated, it has been suggested that they might interact. In
      this study, we summarized the evidence on this interaction by conducting a
      systematic review. Two types of interaction have been discerned, statistical and
      biological interaction, which could give different results. Therefore, we
      calculated both types of interaction for the studies in our review. Cohort
      studies, published between 1999 and 2008, that investigated the effects of
      obesity and physical activity on the risk of type 2 diabetes were included. We
      calculated both biological and statistical interaction in these studies. Eight
      studies were included of which five were suitable to calculate interaction. All
      studies showed positive biological interaction, meaning that the joint effect was
      more than the sum of the individual effects. However, there was inconsistent
      statistical interaction; in some studies the joint effect was more than the
      product of the individual effects, in other studies it was less. The results show
      that obesity and physical inactivity interact on an additive scale. This means
      that prevention of either obesity or physical inactivity, not only reduces the
      risk of diabetes by taking away the independent effect of this factor, but also
      by preventing the cases that were caused by the interaction between both factors.
      Furthermore, this review clearly showed that results can differ depending on what
      method is used to assess interaction.

PMID- 19847654
TI  - Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and
      synthetic cannabimimetics: focus on G-protein-coupled receptors and transient
      receptor potential channels.
AB  - The molecular mechanism of action of Delta(9)-tetrahydrocannabinol (THC), the
      psychotropic constituent of Cannabis, has been a puzzle during the three decades
      separating its characterization, in 1964, and the cloning, in the 1990s, of
      cannabinoid CB1 and CB2 receptors. However, while these latter proteins do
      mediate most of the pharmacological actions of THC, they do not seem to act as
      receptors for other plant cannabinoids (phytocannabinoids), nor are they the
      unique targets of the endogenous lipids that were originally identified in
      animals as agonists of CB1 and CB2 receptors, and named endocannabinoids. Over
      the last decade, several potential alternative receptors for phytocannabinoids,
      endocannabinoids, and even synthetic cannabimimetics, have been proposed, often
      based uniquely on pharmacological evidence obtained in vitro. In particular, the
      endocannabinoid anandamide, and the other most abundant Cannabis constituent,
      cannabidiol, seem to be the most "promiscuous" of these compounds. In this
      article, we review the latest data on the non-CB1, non-CB2 receptors suggested so
      far for endocannabinoids and plant or synthetic cannabinoids, and lay special
      emphasis on uncharacterized or orphan G-protein-coupled receptors as well as on
      transient receptor potential channels.

PMID- 19847657
TI  - Conserved expression of the PRELI domain containing 2 gene (Prelid2) during mid
      later-gestation mouse embryogenesis.
AB  - Prelid2, which belongs to the PRELI domain containing family, is identified as a
      conserved evolution gene. The expression and regulation during embryonic
      development of the prelid2 gene is unknown. In this study, we investigated the
      prelid2 gene expression and regulation using mouse embryos model, by in situ
      hybridization analysis, RT-PCR and bisulfite sequencing. In situ hybridization
      analysis showed that prelid2 gene expression were found in midbrain, spinal cord,
      optic eminence, otic vesicle and tail at E9.5 and E10.5 embryos, in forebrain,
      hindbrain, heart, lung, liver and kidney at E13.5 and E15.5 embryos. Real-time
      quantitative RT-PCR results verified the expression pattern in the four major
      mouse organs, brain, heart, lung, and liver during organs differentiation and
      formation. Bisulfite sequencing illustrated the consistent result of expression
      and its unmethylation status in the genomic promoter region at E12.5, E18.5, and
      new born. Thus, the prelid2 gene is a widely-spread, persistently expressed and
      unmethylated gene in mouse embryonic development. Our results suggest that the
      PRELI domain containing 2 gene is involved in mouse embryonic development.

PMID- 19847658
TI  - Mortality from malignant diseases-update of the Baltimore union poultry cohort.
AB  - We previously studied mortality up to 1989 in 2,639 members of a local union who
      had ever worked in poultry slaughtering and processing plants, because they were
      exposed to oncogenic viruses present in poultry. In this report, cancer mortality
      was updated to the year 2003 for 2,580 of the 2,639 subjects who worked
      exclusively in poultry plants. Mortality in poultry workers was compared with
      that in the US general population through the estimation of proportional
      mortality and standardized mortality ratios separately for each race/sex group
      and for the whole cohort. Compared to the US general population, an excess of
      cancers of the buccal and nasal cavities and pharynx (base of the tongue, palate
      and other unspecified mouth, tonsil and oropharynx, nasal cavity/middle
      ear/accessory sinus), esophagus, recto-sigmoid/rectum/anus, liver and
      intrabiliary system, myelofibrosis, lymphoid leukemia and multiple myeloma was
      observed in particular subgroups or in the entire poultry cohort. We hypothesize
      that oncogenic viruses present in poultry, and exposure to fumes, are candidates
      for an etiologic role to explain the excess occurrence of at least some of these
      cancers in the poultry workers. Larger studies which can control for confounding
      factors are urgently needed to determine the significance of these findings.

PMID- 19847659
TI  - Determinants of inequalities in cervical cancer stage at diagnosis and survival
      in New Zealand.
AB  - OBJECTIVE: The aim of this study is to assess whether ethnic inequalities in
      cervical cancer mortality are due to differences in survival independent of stage
      and age at diagnosis, and to assess the contribution of screening to stage at
      diagnosis. METHODS: Demographic data and cervical screening history were
      collected for 402 women with histologically proven primary invasive cervical
      cancer, diagnosed in New Zealand between 1 January 2000 and 30 September 2002.
      Date of death was available for women who died up to 30 September 2004. RESULTS:
      A Cox proportional hazard model showed that, after adjusting for age, the Maori
      mortality rate was 1.80 times (95% CI 1.07-3.04) that of non-Maori. This reduced
      to 1.25 (95% CI 0.74-2.11) when stage at diagnosis was also adjusted for. Among
      determinants of late stage at diagnosis, older age and being Maori significantly
      increased the risk, while screening was protective. CONCLUSIONS: These results
      indicate that later stage at diagnosis is the main determinant of Maori women's
      higher mortality from cervical cancer. Improving cervical screening among Maori
      women would reduce stage at diagnosis and therefore ethnic inequalities in
      mortality.

PMID- 19847660
TI  - Predicting bioavailability and bioaccumulation of arsenic by freshwater clam
      Corbicula fluminea using valve daily activity.
AB  - There are many bioindicators. However, it remains largely unknown which metal
      bioindicator systems will give the reasonable detection ranges of bioavailable
      metals in the aquatic ecosystem. Various experimental data make the demonstration
      of biomonitoring processes challenging. Ingested inorganic arsenic is strongly
      associated with a wide spectrum of adverse health outcomes. Freshwater clam
      Corbicula fluminea, one of the most commonly used freshwater biomomitoring
      organisms, presents daily activity in valve movement and demonstrates biotic
      uptake potential to accumulate arsenic. Here, a systematical way was provided to
      dynamically link valve daily activity in C. fluminea and arsenic bioavailability
      and toxicokinetics to predict affinity at arsenic-binding site in gills and
      arsenic body burden. Using computational ecotoxicology methods, a valve daily
      rhythm model can be tuned mathematically to the responsive ranges of valve daily
      activity system in response to varied bioavailable arsenic concentration. The
      patterned response then can be used to predict the site-specific bioavailable
      arsenic concentration at the specific measuring time window. This approach can
      yield predictive data of results from toxicity studies of specific bioindicators
      that can assist in prediction of risk for aquatic animals and humans.

PMID- 19847661
TI  - Use of microbial activity measurements for monitoring RBC biofilms.
AB  - Fixed biomass technologies, such as rotating biological contactors or biodiscs,
      have been applied for wastewater depuration both in large and medium-small-sized
      agglomerations. Biofilm's composition and microorganism activity are essential
      parameters for the successful operation and control of these systems. Biofilm's
      thickness and total dry weight have been widely used for biofilm's
      characterization but, actually, are not sufficient to describe biofilm activity.
      In fact, biofilm's activity is not proportional to the quantity of fixed biomass,
      but increases with the thickness of biofilm up to a determined level called the
      "active thickness". Above this level, the diffusion of nutrients through the film
      becomes a limiting factor. A stable, thin, and active biofilm thus offers
      numerous advantages in water and wastewater treatment. Different parameters have
      been used to evaluate biofilm's activity. The specific oxygen uptake rate, INT
      dehydrogenase activity, and the ratio active/total cells have been applied for
      that purpose. These methods are not only simple and rapid but also sensitive,
      precise, and representative. The results obtained confirm the potential of the
      microbial activity measurements studied for an accurate biofilm's
      characterization and biomass activity estimation in fundamental research and for
      the practical operation and control of fixed biomass depuration systems.

PMID- 19847662
TI  - Age, sex and spatial dependent variations in heavy metals levels in the Glaucous
      Gulls (Larus hyperboreus) from the Bjornoya and Jan Mayen, Arctic.
AB  - Heavy metals (Cd, Cu, Fe, Mn and Zn) concentrations were determined in different
      tissues (muscle, kidney, liver, brain, gonads, heart and feathers) of Glaucous
      Gulls (Larus hyperboreus) from Bjornoya and Jan Mayen. The age and spatial
      dependent variations in heavy metals were quantified and interpreted in view of
      the three chemometric techniques, i.e. non-parametric Mann-Whitney U test,
      redundancy gradient analysis and detrended correspondence analysis. The Glaucous
      Gulls from Bjornoya contained significantly higher (p < 0.05) levels of Cd, Cu
      and Zn than those inhabited Jan Mayen. Adult birds were characterized by greater
      (p < 0.01) concentration of muscle, hepatic and renal heavy metals in comparison
      to chicks. Insignificantly higher slope constant Zn/Cd for the liver than for the
      kidney may reflect insignificant Cd exposure. Estimate of transfer factor (TF)
      allows us to assess variations in heavy metal concentrations during the
      individual development of Glaucous Gulls. It may be stated that there is a
      distinct increase of bioaccumulation of all the studied metals during subsequent
      stages of the bird life.

PMID- 19847663
TI  - Total metal levels in crayfish Astacus leptodactylus (Eschscholtz, 1823), and
      surface sediments in Lake Terkos, Turkey.
AB  - The aim of this study was to determine the total metal accumulation (aluminium,
      copper, manganese, lead, cadmium and iron) in different organs and eggs of
      Astacus leptodactylus (Eschscholtz, 1823) and sediments total metal contents
      (aluminium, copper, manganese, lead, cadmium, iron, zinc, chromium, nickel) in
      Lake Terkos. Water and sediment samples were collected from two stations at two
      different depths (1 and 2 m) of Lake Terkos in May 2008. Crayfish samples were
      collected by trammel net at the same region. Primary hydrographic conditions,
      such as temperature (13.6-19.4 degrees C), salinity (0.27-0.34 per thousand),
      dissolved oxygen (7.04-12.30 mg l(-1)) and pH (7.42-8.51), were recorded for each
      sampling point. Moreover, the total organic carbon (1.65-5.44%) and the total
      calcium carbonate contents (19.44-41.16%) of sediment samples were determined.
      According to the Turkish Food Codex (J Zool 26:283-288, 2002), the maximum
      allowable Pb and Cd levels in crayfish are 0.5 mg/kg wet weight. Accordingly, the
      Pb and Cd levels determined in A. leptodactylus samples are below this limit.
      However, when compared with the acceptable metal limits defined by WHO,
      Australian National Health and Medical Research Council and Ministry of
      Agriculture in United Kingdom (UK), it is clear that the Cu level is at the limit
      and the Cd results exceed the limit. When the metal contents in sediment samples
      from Lake Terkos are examined, it is seen that the Al, Fe, Mn, Ni and Cu contents
      are lower while Zn, Cr, Cd and Pb contents are higher than the crustal average
      values. The high values draw attention to the land-based domestic and industrial
      inputs. Lake Terkos sediments have high enrichment factors (EF) of Zn, Cr, Cd and
      Pb metals which corroborate this result. The low EFs of Fe, Ni and Cu are due to
      the natural (terrigeneous) inputs. Additionally, there is no Al, Fe, Ni and Cu
      metal enrichment in these lake sediments because of the low contamination factor
      (CF) values. However, it is moderately contaminated by Zn, Cr and Pb, and heavily
      contaminated by Cd.

PMID- 19847664
TI  - Improving statistical distinctness in assessing trophic levels: the development
      of simulated normal distributions.
AB  - The statistical distinctness in assessing differences of the trophic status
      between sampling sites was investigated in the present study. Nutrient
      (phosphate, nitrate, nitrite, ammonia) and phytoplankton (chlorophyll, cell
      number) variables from nine sampling stations were used for the validation of the
      statistical procedures. Raw data, transformed data, and simulated data derived on
      normalized nutrient-phytoplankton frequency distribution were tested. The Kruskal
      Wallis (KW) nonparametric statistical procedure was also applied on the raw data
      as well as the analysis of variance on transformed and simulated data. In all
      cases, pairwise comparisons for each parameter between stations were performed.
      The results showed that maximum distinctness between sampling sites for all the
      six variables was attained using the simulated data. The KW method showed the
      poorest discrimination between stations. The methodology of producing and using
      simulated data is described step by step, and the advantages in cases of unequal
      sampling design or small sample size are discussed.

PMID- 19847665
TI  - Regulation of the seasonal population patterns of Helicoverpa armigera moths by
      Bt cotton planting.
AB  - Transgenic cotton expressing the Bacillus thuringiensis (Bt) Cry1Ac toxin has
      been commercially cultivated in China since 1997, and by 2000 Bt cotton had
      almost completely replaced non-transgenic cotton cultivars. To evaluate the
      impact of Bt cotton planting on the seasonal population patterns of cotton
      bollworm, Helicoverpa armigera, the dynamics of H. armigera moths were monitored
      with light traps from four locations (Xiajin, Linqing and Dingtao of Shandong
      Province; Guantao of Hebei Province) in high Bt density region and five locations
      (Anci and Xinji of Hebei Province; Dancheng and Fengqiu of Henan Province; Gaomi
      of Shandong Province) in low Bt density region from 1996 to 2008. A negative
      correlation was found between moth densities of H. armigera and the planting
      years of Bt cotton in both high and low Bt density areas. These data indicate
      that the moth population density of H. armigera was reduced with the introduction
      of Bt cotton in northern China. Three generations of moths occurred between early
      June and late September in the cotton regions. Interestingly, second-generation
      moths decreased and seemed to vanish in recent years in high Bt density region,
      but this tendency was not found in low Bt density region. The data suggest that
      the planting of Bt cotton in high Bt density region was effective in controlling
      the population density of second-generation moths. Furthermore, the seasonal
      change of moth patterns associated with Bt cotton planting may regulate the
      regional occurrence and population development of this migratory insect.

PMID- 19847666
TI  - Consumption of pasteurized human lysozyme transgenic goats' milk alters serum
      metabolite profile in young pigs.
AB  - Nutrition, bacterial composition of the gastrointestinal tract, and general
      health status can all influence the metabolic profile of an organism. We
      previously demonstrated that feeding pasteurized transgenic goats' milk
      expressing human lysozyme (hLZ) can positively impact intestinal morphology and
      modulate intestinal microbiota composition in young pigs. The objective of this
      study was to further examine the effect of consuming hLZ-containing milk on young
      pigs by profiling serum metabolites. Pigs were placed into two groups and fed a
      diet of solid food and either control (non-transgenic) goats' milk or milk from
      hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the
      feeding period and global metabolite profiling was performed. For a total of 225
      metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels
      of 18 known and 4 unknown metabolites differed significantly between the two
      groups with the direction of change in 13 of the 18 known metabolites being
      almost entirely congruent with improved health status, particularly in terms of
      the gastrointestinal tract health and immune response, with the effects of the
      other five being neutral or unknown. These results further support our hypothesis
      that consumption of hLZ-containing milk is beneficial to health.

PMID- 19847667
TI  - Predictors of ventricular arrhythmias in patients with mitral valve prolapse.
AB  - Arrhythmias have been reported to occur frequently in symptomatic patients with
      mitral valve prolapse (MVP). The mechanisms causing ventricular arrhythmias in
      patients with MVP have not been fully investigated. The purpose of this study was
      to determine the clinical, echocardiographic and heart rate variability
      parameters, and plasma concentrations of electrolytes and inflammatory markers in
      predicting ventricular arrhythmias in patients with MVP. A total of 58
      consecutive patients with MVP were included in this study. We performed
      electrocardiography, echocardiography, holter analysis, routine biochemical tests
      including plasma concentrations of electrolytes and inflammatory markers, and
      evaluated the clinical characteristics. Ventricular arrhythmia defined as
      occurrence of any of the followings: ventricular premature contractions (VPCs),
      VPC couplets, and ventricular tachycardia documented by holter analysis,
      continuous monitoring or by electrocardiography. Twenty patients (34%) had
      ventricular arrhythmias, and 38 (66%) patients had no ventricular arrhythmias.
      Seventeen patients had VPC, 2 patients had VPC couplets and 1 patient had
      ventricular tachycardia. Univariable predictors of ventricular arrhythmias
      included isovolumetric relaxation time and the occurrence of moderate to severe
      mitral regurgitation. Multivariable logistic regression analysis showed that
      occurrence of moderate to severe mitral regurgitation was the only independent
      predictor of ventricular arrhythmias (relative risk: 8.42, 95% confidence
      interval: 1.49-47.64, p = 0.01). Present study showed that the only independent
      predictor of ventricular arrhythmias in patients with MVP is the occurrence of
      moderate to severe mitral regurgitation.

PMID- 19847668
TI  - Urban pigeons (Columba livia) as a potential source of pathogenic yeasts: a focus
      on antifungal susceptibility of Cryptococcus strains in Northeast Brazil.
AB  - To investigate pigeons as a potential source of pathogenic yeast species, 47
      samples of pigeon droppings and 322 samples from pigeon cloacae were evaluated.
      The samples were also collected from trees located near the pigeon habitats, in
      the city of Fortaleza, Ceara, Northeast Brazil. In addition, we evaluated the in
      vitro antifungal susceptibility of these environmental Cryptococcus strains to
      amphotericin B, azoles and caspofungin. C. neoformans var. neoformans (n = 10),
      C. laurentii (n = 3), Candida spp. (n = 14), Rhodotorula mucilaginosa (n = 6) and
      Trichosporon sp. (n = 3) were isolated from pigeon droppings. In contrast, only
      Candida spp. (n = 4), Trichosporon sp. (n = 3) and R. mucilaginosa (n = 2) were
      recovered from cloacae specimens. Only Candida glabrata (n = 1) was recovered
      from plant samples. Azole resistance was detected in only one environmental
      strain of Cryptococcus, which was resistant to itraconazole (MIC = 1 microg/ml).
      As expected, all Cryptococcus strains were resistant to caspofungin. In summary,
      the present study confirms that urban pigeons are a potential source of
      Cryptococcus spp. and other pathogenic yeasts. Additionally, antifungal
      resistance was observed in one environmental strain of Cryptococcus neoformans
      var. neoformans in Northeast Brazil.

PMID- 19847669
TI  - Aldose reductase is a potent regulator of TGF-beta1 induced expression of
      fibronectin in human mesangial cells.
AB  - Glomerulosclerosis is considered to be the final pathway leading to the
      progressive loss of renal function in several kidney diseases, transforming
      growth factor beta1 (TGF-beta1) plays a critical role in glomerulosclerosis.
      However, the mechanisms of TGF-beta1 stimulating glomerulosclerosis remain poorly
      understood. Here we report that TGF-beta1-induced expression of fibronectin (FN)
      depends on the activity of aldose reductase (AR) in human mesangial cells
      (HMCs).The results show that TGF-beta1 increased the expression of FN, which
      attenuated by pharmacological inhibition of AR or knockdown of the enzyme by
      small interfering RNA (siRNA). MAPKs (ERK, JNK and p38) signalling pathways were
      activated in HMCs after stimulated by TGF-beta1, inhibition of AR blunted the
      activation ERK, p38 and JNK signalling pathways. These changes were associated
      with decreased TGF-beta1-induced expression of FN. These results indicate that AR
      is a potent regulator of TGF-beta1 induced expression of FN in human mesangial
      cells: it suggests that inhibition of this enzyme may be useful to prevented
      extracellular matrix (ECM) deposition in glomerulosclerosis.

PMID- 19847670
TI  - Does urinary incontinence affect quality of life of Greek women less severely? A
      cross-sectional study in two Mediterranean settings.
AB  - OBJECTIVE: Numerous studies have identified a reduced health-related quality of
      life (QoL) in patients with urinary incontinence (UI). The aim of this study was
      to assess and compare QoL in women with UI in the island of Crete, Greece, and in
      Turkey. METHODS: Incontinent women from two community-based primary health care
      (PHC) groups (Greece and Turkey) and one outpatient clinic-based group were
      studied. RESULTS: A total of 231 (24.7%) women out of 932 women from the PHC
      group in Greece and Turkey reported UI whereas another 38 incontinent women
      visited the secondary care outpatient clinic. Mean Incontinence Quality of Life
      questionnaire (I-QoL) total score of women visiting PHC centers was 73.8 (SD =
      23.5). There was significant difference among the three groups regarding I-QoL
      total and subscale scores, with women from the Greek community-based group having
      the highest score (mean = 81.8, SD = 20.7, P < 0.001). Impaired QoL was
      significantly associated with severity (P < 0.001), incontinence type (P =
      0.026), seeking secondary care, and Turkey as sample setting (P < 0.001).
      CONCLUSION: Urinary incontinence is a frequent problem for women visiting PHC
      centers, affecting negatively their quality of life. Besides incontinence
      severity, Turkey as place of residence emerged as another essential predictor of
      impaired quality of life, suggesting that other social and cultural factors may
      also play an important role.

PMID- 19847671
TI  - Climate change, responsibility, and justice.
AB  - In this paper I make the following claims. In order to see anthropogenic climate
      change as clearly involving moral wrongs and global injustices, we will have to
      revise some central concepts in these domains. Moreover, climate change threatens
      another value ("respect for nature") that cannot easily be taken up by concerns
      of global justice or moral responsibility.

PMID- 19847672
TI  - Risk and responsibility in a manufactured world.
AB  - Recent criticisms of traditional understandings of risk, responsibility and the
      division of labour between science and politics build on the idea of the co
      produced character of the natural and social orders, making a case for less
      ambitious and more inclusive policy processes, where questions of values and
      goals may be addressed together with questions of facts and means, causal
      liabilities and principled responsibilities. Within the neo-liberal political
      economy, however, the contingency of the world is depicted as a source of
      unprecedented opportunities for human craftsmanship, rather than of possibly
      unmanageable surprises. Gene technologies offer a vantage point for reflecting on
      the consequences of the drift from discovery to invention as a master frame in
      the appraisal of human intermingling with the world. Biotech patenting
      regulations carve out a sovereign agency which, by crafting nature, also crafts
      the distinction between the manufactured and non-manufactured world. Difficulties
      in ascribing responsibility stem as a consequence. It is likely that politics and
      economy can be democratized and responsibilities rearranged not by
      'democratizing' knowledge production, but rather the reverse.

PMID- 19847673
TI  - Endothelin-1 as a neuropeptide: neurotransmitter or neurovascular effects?
AB  - Endothelin-1 (ET-1) is an endothelium-derived peptide that also possesses potent
      mitogenic activity. There is also a suggestion the ET-1 is a neuropeptide, based
      mainly on its histological identification in both the central and peripheral
      nervous system in a number of species, including man. A neuropeptide role for ET
      1 is supported by studies showing a variety of effects caused following its
      administration into different regions of the brain and by application to
      peripheral nerves. In addition there are studies proposing that ET-1 is
      implicated in a number of neural circuits where its transmitter affects range
      from a role in pain and temperature control to its action on the hypothalamo
      neurosecretory system. While the effect of ET-1 on nerve tissue is beyond doubt,
      its action on nerve blood flow is often ignored. Here, we review data generated
      in a number of species and using a variety of experimental models. Studies range
      from those showing the distribution of ET-1 and its receptors in nerve tissue to
      those describing numerous neurally-mediated effects of ET-1.

PMID- 19847674
TI  - Functional variants of glucokinase regulatory protein and apolipoprotein A5 genes
      in ischemic stroke.
AB  - Both the natural variants of the apolipoprotein A5 (APOA5) and the glucokinase
      regulatory protein gene (GCKR) have been shown to associate with increased
      fasting triglyceride levels. Here, we investigated the possible association of
      the functional variants of these two genes with non-fasting triglyceride levels
      and their susceptibility nature in ischemic stroke. A total of 513 stroke
      patients and 172 healthy controls were genotyped. All the APOA5 variants (T
      1131C, IVS3 + G476A, C56G, and T1259C) were associated with increased
      triglyceride levels in all stroke patients and controls; except for T1259C, they
      all conferred risk for the disease. No such association was found for the
      examined GCKR rs1260326 (C1337T) variant. Furthermore, we examined the effects of
      specific combinations of the GCKR rs1260326 and APOA5 polymorphisms. Our findings
      confirmed the previous results regarding the association of APOA5 variants with
      triglyceride-level increase and stroke susceptibility of these alleles. By
      contrast, we could not detect any association of the studied GCKR allele with
      triglyceride levels or with the susceptibility of stroke in the same cohort of
      patients. In addition, the effect of APOA5 did not change significantly when
      specific combinations of the two genes were present.

PMID- 19847675
TI  - Brain tissue oxygenation in children diagnosed with brain death.
AB  - BACKGROUND: Diagnosing brain death in children is challenging. Guidelines
      recommend using confirmatory testing to provide ancillary information to support
      the diagnosis. Brain tissue oxygenation (PbtO(2)) is being increasingly used in
      the adult neurocritical care for continuous monitoring of the adequacy of brain
      oxygenation; however, data in pediatrics is limited. Evidence from adult studies
      suggests that persistent PbtO(2) of 0 mmHg is associated with brain death, but
      this relationship has not yet been demonstrated in children; therefore, we
      examined our experience with PbtO(2) monitoring and brain death in children with
      acute neurological pathology. METHODS: We retrospectively reviewed patient
      records from a prospectively maintained database of 85 children who were
      ventilated for coma due to acute neurological injury and who received
      intracerebral monitoring. RESULTS: We identified five children who had suffered
      brain death while being monitored. PbtO(2) had decreased to 0 mmHg in all five
      children at the time of brain death diagnosis. In contrast, PbtO(2) in patients,
      who did not develop brain death, never decreased to 0 mmHg. We review the
      benefits and drawbacks of using brain tissue oxygenation as ancillary information
      in diagnosing brain death in children. CONCLUSIONS: Preliminary data from this
      study suggest that PbtO(2) decreases to 0 mmHg when brain death occurs in
      children. Further study is needed to determine the limitations, and the
      sensitivity and specificity of this finding in a larger group of children.

PMID- 19847676
TI  - Atypical acute hemorrhagic leukoencephalitis (Hurst's disease) presenting with
      focal hemorrhagic brainstem lesion.
AB  - BACKGROUND: Acute hemorrhagic leukoencephalitis (AHL; Hurst's disease) is a rare,
      severe, inflammatory CNS disease that is typically diffuse, multifocal and
      associated with petechial hemorrhage. The objective of this study is to report
      the clinical, radiologic, and pathologic findings in a fatal AHL case with focal
      brainstem involvement and gross hemorrhage. METHODS: Patient evaluation in a
      tertiary neurointensive care unit with serial brain magnetic resonance imaging
      (MRI) and neuropathological examination on autopsy were performed. RESULTS: The
      patient presented with mild, then rapidly worsening, brainstem impairment to a
      locked-in syndrome. Brain MRI demonstrated an isolated gadolinium enhancing
      brainstem lesion that enlarged dramatically over weeks and was associated with
      gross hemorrhage and necrosis. The patient died despite aggressive treatment with
      intravenous corticosteroids and plasma exchange. Autopsy demonstrated the
      isolated severe necrotic lesion consistent with AHL. CONCLUSIONS: AHL may present
      as a solitary brainstem lesion with gross hemorrhage and should be considered in
      patients with isolated enhancing brainstem lesions. AHL may be fatal even despite
      early, aggressive immunomodulatory therapy.

PMID- 19847677
TI  - Acute granulomatous acanthamoeba encephalitis in an immunocompetent patient.
AB  - BACKGROUND: Acanthamoeba sp. are known to cause fatal granulomatous Acanthamoeba
      encephalitis (GAE) in immunocompromised patients. METHODS: The case of a 17 year
      old immunocompetent patient with acute purulent meningoencephalitis is reported.
      RESULTS: After substantial improvement of cerebrospinal fluid under conventional
      antimicrobial treatment the patient was suffering several relapses. The causative
      agent was identified as Acanthamoeba lenticulata T5 which entered the CNS through
      a bone dehiscence of ethmoidal cells. Due to severe vasospasm the patient
      developed multiple strokes, which led to marked neurologic sequels. CONCLUSIONS:
      This case report demonstrates successful treatment of usually lethal GAE in an
      immunocompetent patient with high dose meropenem, linezolid, moxifloxacin and
      fluconazole followed by a partially adapted antimicrobial combination therapy.

PMID- 19847678
TI  - Intracranial tumor lysis and cerebral edema after administration of intrathecal
      methotrexate: a case report and discussion.
AB  - Methotrexate is a common agent used in the management of hematological
      malignancies, but is often associated with the development of diverse central
      nervous system adverse events, such as seizures. We present a case of seizures
      after intrathecal administration of methotrexate, during the management of
      diffuse large B-cell lymphoma. There was complete resolution of the CNS lesions
      after chemotherapy along with the interval development of diffuse cerebral edema.
      We hypothesize that tumor lysis is the underlying mechanism of this untoward
      event, resulting in the corresponding clinical presentation.

PMID- 19847679
TI  - The effect of peripheral blood values on prognosis of patients with locally
      advanced gastric cancer before treatment.
AB  - We aimed to investigate the prognostic significance of neutrophil, lymphocyte,
      platelet, mean platelet value (MPV), platelet-lymphocyte ratio (PLR) and
      neutrophil-lymphocyte ratio (NLR) in patients with locally advanced gastric
      cancer (LAGC). One hundred sixty-eight patients with LAGC who had been followed
      up between 2004 and 2008 were included in present study. The results of
      hematological (platelet, lymphocyte, neutrophil and MPV) and biochemical (uric
      acid and LDH) parameters were evaluated before treatment. NLR was divided into
      two groups as <2.56 and >=2.57 and PLR was also divided into two groups as <=160
      and >160. Platelet counts and lymphocyte counts were also divided into two
      groups; <=300.000/mm3 and >300.000/mm3, and <1,500/mm3 and >=1,500/mm3,
      respectively. Results were evaluated with Kaplan-Meier and Long-rank tests. The
      mean age of patients at diagnosis was 60.1+/-12.1 and 114 of patients (67.8%)
      were male. For 168 patients, 48 months overall survival (OS) rate was 45.2% and
      the median OS was 39 months (range 33-44). In patients whose PLR was less than
      160 (n=54), the median OS was 45 months (range 38-52) and also for cases whose
      PRL was greater than 160 (n=114), the median OS was 27 months (range 22-32)
      (p=0.006). While for fifty patients whose lymphocyte counts were less than 1,500,
      the median OS was 27 months (range 21-33), in cases with high lymphocyte counts
      (>=1,500) (n=118), it was 41 months (range 35-48) (p=0.03). The median OS was 41
      (range 34-48) and 30 (range 23-37) months in two platelets groups, respectively
      (p=0.24). However, in the patients whose NLR was less than 2.56 (n=107), median
      OS was better than with cases whose NLR was greater than or equal to 2.56 (42 vs.
      27 months). Routine peripheral blood counts may be useful prognostic factor for
      evaluating the accuracy of risk stratification in patients with radically
      resected gastric cancer Our results need to be confirmed by study including
      larger sample size in future.

PMID- 19847681
TI  - Requirements for ethics approvals.

PMID- 19847680
TI  - Thrombotic microangiopathy following docetaxel and trastuzumab chemotherapy: a
      case report.
AB  - Thrombotic microangiopathy is a rare haematological emergency which encompasses
      the conditions of haemolytic uraemic syndrome (HUS) and thrombotic
      thrombocytopenic purpura (TTP). It is an unusual but recognised complication of
      chemotherapy. It has not previously been described in conjunction with docetaxel
      or trastuzumab therapy. We report a 47-year-old patient with localised breast
      cancer who developed thrombotic microangiopathy (HUS/TTP) acutely following
      concurrent neoadjuvant therapy with trastuzumab and docetaxel. We demonstrate
      from our case that mild confusion occurring on a background of mild anaemia and
      thrombocytopenia may sometimes be the only clue to the diagnosis. Clinicians
      should be aware of the possibility of thrombotic microangiopathy associated with
      trastuzumab and docetaxel therapy, as early intervention can improve clinical
      outcome.

PMID- 19847682
TI  - Effect of cold-water immersion duration on body temperature and muscle function.
AB  - This study compared the effect of 5, 10 and 20 min of cold-water (14 degrees C)
      immersion on rectal and muscle temperature and neuromuscular function. Twelve
      cyclists performed four cycling time-to-exhaustion trials in hot conditions (40
      degrees C and 40%rh), followed 25 min later by cold-water immersion for 5, 10 or
      20 min or 20 min in room temperature (24 degrees C; control). Rectal temperature
      was measured continuously, and muscle temperature was measured before,
      immediately after and 45 min after the time-to-exhaustion-test, as well as before
      and after water immersion. Sixty-second maximal voluntary isometric torque and
      isokinetic torque of the knee extensors were measured before, immediately after
      and 55 min after time-to-exhaustion-test. A greater rate of decrease in rectal
      temperature was observed in all water immersion conditions 45-80 min after time
      to-exhaustion-test compared with control. Compared with control, muscle
      temperature 45 min after time-to-exhaustion-test was lower for all water
      immersion conditions; however, muscle temperature was lower for the 10- and 20
      min conditions compared with 5 min. Isometric torque measured 55 min after time
      to-exhaustion-test was lower for all conditions. Isokinetic torque was lower for
      all conditions immediately and 55-min post-time-to-exhaustion-test. Of the
      durations measured, 5 min of cold-water immersion appeared as the most
      appropriate duration for reducing rectal temperature but limiting decreases in
      muscle temperature.

PMID- 19847683
TI  - The influence of parenting practices and parental presence on children's and
      adolescents' pre-competitive anxiety.
AB  - We examined parental influence on athletes' pre-competitive anxiety. The effect
      of parental presence during competition was studied as was the role of parenting
      practices. Data were collected from a sample of 341 athletes (201 basketball
      players and 140 tennis players) before an official competition. Analysis of
      variance indicated that the presence of both parents was associated with higher
      pre-competitive anxiety for all participants, except male tennis players. The
      absence of both parents did not result in less anxiety. A second analysis of
      variance revealed that females tennis players at provincial and national level
      perceived greater parental pressure than most other participants. Canonical
      correlation analysis showed a positive relationship between pre-competitive
      anxiety and parenting practices for tennis players, but not for basketball
      players. Directive behaviours and pressure were positively associated with pre
      competitive anxiety for all tennis players, whereas praise and understanding was
      negatively related to anxiety for female tennis players only.

PMID- 19847684
TI  - Factors associated with physical activity referral completion and health
      outcomes.
AB  - Participant socio-demographic characteristics and referral reason were
      investigated in relation to completion and health outcomes in a Primary Care
      Physical Activity Referral Scheme using a prospective population-based
      longitudinal design. Participants (n = 1735) were recruited over a 2-year period.
      A three-stage binary logistic regression analysis identified the factors
      associated with the outcomes of completion (model 1), body mass reduction (model
      2) and blood pressure reduction (model 3). Participant's age, gender, ethnicity,
      occupation and referral reason were the independent variables for model 1, with
      the variables of completion added in model 2 and completion and body mass
      reduction added in model 3. Logistic regression analysis revealed that increasing
      age is associated with the likelihood of completion (Odds Ratio, OR = 1.019;
      Confidence Interval, CI = 1.008-1.030; P = 0.001). Participants with a pulmonary
      condition are less likely to complete (OR = 0.546; CI = 0.346-0.860; P < 0.01)
      compared to those referred for cardiovascular conditions. For ethnicity, in
      comparison to the white category, patients in the mixed category are
      significantly more likely to achieve a reduction in body mass (OR = 3.991; CI =
      1.191-13.373; P < 0.05). Those who complete are more likely to achieve a
      reduction in body mass (OR = 3.541; CI = 2.721-4.608; P < 0.001). When compared
      to the unemployed category, the skilled manual category had an increased
      likelihood of achieving a reduction in blood pressure (OR = 1.875; CI = 1.044
      3.227; P < 0.05). Participants who completed also demonstrated an increased
      likelihood of a reduction in blood pressure (OR = 1.680; CI = 1.250-2.003; P <
      0.001). Furthermore, those participants who achieved a reduction in body mass had
      an increased likelihood of achieving a reduction in blood pressure (OR = 1.292;
      CI = 1.008-1.641; P < 0.05). Completion is associated with health outcomes of
      reduced body mass and blood pressure.

PMID- 19847685
TI  - Body composition of English Premier League soccer players: influence of playing
      position, international status, and ethnicity.
AB  - Body composition is a key consideration in the physical make-up of professional
      soccer players. The aims of the present study were to determine whether the body
      composition of professional soccer players varied according to playing position,
      international status or ethnicity, and to establish which variables best
      distinguished the soccer players from a reference group. Body composition was
      assessed using dual-energy X-ray absorptiometry in 64 male professional soccer
      players. Measured variables included bone mineral density and the relative
      amounts of lean and fat mass. Data were analysed using analysis of variance and
      stepwise discriminant function. The soccer players recorded better values than a
      reference group (n = 24) for all body composition compartments. Percent lean mass
      and bone mineral density were the variables best able to identify the soccer
      players (95.5% correctly classified). Differences in body composition were
      evident between goalkeepers and outfield players, but not between outfield
      playing positions. No differences were found on the basis of international
      status. The non-Caucasian players demonstrated significantly lower percent body
      fat (9.2 +/- 2.0%) than the Caucasian players (10.7 +/- 1.8%). It was concluded
      that body composition is important for elite soccer players, but that homogeneity
      between players at top professional clubs results in little variation between
      individuals.

PMID- 19847686
TI  - Differences in body composition and risk of lifestyle-related diseases between
      young and older male rowers and sedentary controls.
AB  - The aim of this cross-sectional study was to compare body composition and risk
      factors of lifestyle-related diseases between young and older male rowers and
      sedentary controls. Healthy males aged 19-73 years participated in the study, and
      were divided into four groups: 26 young rowers, 24 senior rowers, 23 young
      sedentary controls, and 22 senior sedentary controls. Total and regional lean
      soft tissue, fat mass, and bone mineral density were measured using dual-energy X
      ray absorptiometry. The HDL-cholesterol of senior rowers (67.4 +/- 13.4 mg . dl(
      1)) was significantly (P < 0.05) higher than that of senior sedentary controls
      (59.2 +/- 11.9 mg . dl(-1)), while HDL-cholesterol was similar in senior rowers
      and young rowers (66.1 +/- 10.8 mg . dl(-1)). Arm, leg, and trunk lean soft
      tissue mass were significantly higher in senior rowers (5.6 +/- 0.6 kg, 18.2 +/-
      1.8 kg, and 27.3 +/- 3.2 kg respectively) than in senior sedentary controls (5.1
      +/- 0.4 kg, 16.3 +/- 1.4 kg, and 24.6 +/- 1.7 kg respectively; P < 0.05). Bone
      mineral density was also significantly higher in senior rowers than in senior
      sedentary controls (ribs, lumbar spine, and pelvic segments; P < 0.05). We
      conclude that age-related increases in the risk of lifestyle-related diseases,
      such as osteoporosis and sarcopenia, are attenuated in male rowers. These results
      suggest that regular rowing exercise may have a positive influence in the
      prevention of lifestyle-related diseases in older Japanese people.

PMID- 19847687
TI  - Is there an influence of relative age on participation in non-physical sports
      activities? The example of shooting sports.
AB  - The aims of this study were to test for the presence of a relative age effect
      among male (n = 119,715) and female (n = 12,823) members of the shooting sports
      federation, and to determine whether any such effect has an impact on dropout
      from the sport. For the boys and girls, the results show a uniform distribution
      of dropout. A relative age effect was not found for the girls, showing that in
      female shooting sports there is no such effect. For the males, a significant
      statistical relative age effect was not detected in the 18-20 and 13-14 year
      categories. However, a relative age effect was found among adults and the 11-12
      and under 11 year categories. A significant "inverse" relative age effect was
      found for the 15-17 year group. Further qualitative research is needed to clarify
      which factors contribute to this asymmetric distribution of birth dates in French
      male shooting sports.

PMID- 19847688
TI  - Analysis of elite swimmers' activity during an instrumented protocol.
AB  - The aim of this study was to examine swimmers' activity-technical device coupling
      during an experimental protocol (MAD-system). The study was conducted within a
      course-of-action theoretical and methodological framework. Two types of data were
      collected: (a) video recordings and (b) verbalizations during post-protocol
      interviews. The data were processed in two steps: (a) reconstruction of each
      swimmer's course of action and (b) comparison of the courses of action. Analysis
      from the actors' point of view allowed a description of swimmer-technical device
      coupling. The results showed that the technical device modified the athletes'
      range of perceptions and repertoire of actions. They also indicated that changes
      in coupling between the swimmers and the MAD-system were linked to utilization
      constraints: the swimmers' experiences were transformed in the same speed
      intervals, suggesting that this was an essential situational constraint to
      swimmer-technical device coupling. This study highlights how a technical device
      and the conditions of its use changed athletes' activity and suggests that it is
      important to develop activity-centred design in sport.

PMID- 19847689
TI  - Telic dominance influences affective response to a heavy-intensity 10-min
      treadmill running session.
AB  - In this paper, we examine the hypothesis that telic dominance is one of the
      psychological variables that may influence the exercise-affect relationship
      according to the dual-mode model of exercise and affect (Ekkekakis, 2003). Thirty
      three participants with high or low telic dominance rated their affect at 3-min
      intervals as they ran on a treadmill while the speed was adjusted to maintain
      their respiratory exchange ratio at a target value of 1.00 +/- 0.02 for a period
      of 10 min. Compared with baseline scores (which were not statistically different
      between the two groups), the mean decline in pleasure at the end of the run was
      twofold greater in participants with high telic dominance. This was observed
      after having controlled for individual differences in aerobic fitness (as
      measured by [Vdot]O(2max)). We also detected an earlier onset of decreases in
      pleasure in high telic dominant participants. Our data extend the burgeoning
      research on variables influencing one's ability to continue exercising at an
      imposed intensity that can produce pain or discomfort (i.e. tolerance of exercise
      intensity). Additionally, results from this study support continued promotion of
      tailor-made prescriptions for maximizing positive affective outcomes during
      exercise, which ultimately may lead to increased adherence to an exercise
      programme.

PMID- 19847690
TI  - Fatigue in a simulated cross-country skiing sprint competition.
AB  - The aim of this study was to assess fatigue during a simulated cross-country
      skiing sprint competition based on skating technique. Sixteen male skiers
      performed a 30-m maximal skiing speed test and four 850-m heats with roller skies
      on a tartan track, separated by 20 min recovery between heats. Physiological
      variables (heart rate, blood lactate concentration, oxygen consumption), skiing
      velocity, and electromyography (EMG) were recorded at the beginning of the heats
      and at the end of each 200-m lap during the heats. Maximal skiing velocity and
      EMG were measured in the speed test before the simulation. No differences were
      observed in skiing velocity, EMG or metabolic variables between the heats. The
      end (820-850 m) velocities and sum-iEMG of the triceps brachii and vastus
      lateralis in the four heats were significantly lower than the skiing velocity and
      sum-iEMG in the speed test. A significant correlation was observed between mean
      oxygen consumption and the change in skiing velocity over the four heats. Each
      single heat induced considerable neuromuscular fatigue, but recovery between the
      heats was long enough to prevent accumulation of fatigue. The results suggest
      that the skiers with a high aerobic power were less fatigued throughout the
      simulation.

PMID- 19847691
TI  - Swimming intensity during triathlon: a review of current research and strategies
      to enhance race performance.
AB  - The swim section of Sprint- and Olympic-distance triathlon race formats is
      integral to the success of subsequent cycle and running disciplines, and to
      overall race performance. The current body of swimming-based triathlon research
      suggests that the energy used, and the positioning gained among competitors
      during the swim, is important in determining the success of an athlete's race,
      especially professional athletes in draft-legal settings. Furthermore, by
      swimming at a reduced intensity, it has been shown that the performance of the
      subsequent disciplines may be enhanced. However, reductions in energy output can
      be obtained without compromising swimming speed. This review highlights the
      importance of swimming intensity during a triathlon and how it impacts on the
      ensuing cycle and run. Furthermore, consideration is given to current methods
      used to manipulate swimming performance.

PMID- 19847692
TI  - Load, stress, and recovery in adolescent rugby union players during a competitive
      season.
AB  - Despite increased professionalization of adolescent sport and improved
      articulation to elite adult participation, the impact of sports such as rugby
      union among adolescents is under-explored. This study describes psychological
      stress-recovery responses relative to training loads in 106 male adolescent rugby
      union players. The results showed that players with the highest training and
      physical activity volumes during the season demonstrated more favourable recovery
      stress states than moderate- and low-volume groups. Stress and under-recovery did
      not increase with increases in weekly volume when assessed across a season. When
      assessed more acutely during intensive competition phases, stress and under
      recovery increased with increases in participation demands. Despite better
      psychological stress and recovery profiles of more elite, higher-load players,
      not all participants demonstrated favourable capacities to deal with stress and
      recovery processes. Seven participants were in at least two of three categories
      of highest volume, highest stress, and poorest recovery. Even in the absence of a
      full understanding of the impact of high-volume, high-stress, poor-recovery
      participation among adolescent athletes, these markers may be precursors for more
      deleterious outcomes such as injury, performance decrements, and overtraining.
      Findings support the efficacy of serially monitoring young athletes.

PMID- 19847693
TI  - Activity profiles and physical demands of elite women's water polo match play.
AB  - The aim of this study was to quantify the movement patterns of contemporary elite
      women's water polo match play. Thirty-three player matches (centre, n = 15 and
      perimeter, n = 18) were analysed using video-based time-motion analysis.
      Frequency and duration of individual movements and distance swum were assessed.
      Mean match time and playing time were 69:48 +/- 04.30 min:s and 33:14 +/- 14:40
      min:s, respectively. Players performed 330 +/- 158 discrete movements per match,
      representing a change in movement every 6.2 s. There were 54 +/- 25 high
      intensity activities per match, or one every 38.4 s. These findings characterise
      women's water polo as a high-intensity intermittent sport. Total distance swum
      per match was 699.3 +/- 296.8 m. Positional differences showed a predominance of
      wrestling in centre players (4:13 vs. 1:53 min:s; P < 0.001) and sprint swimming
      in perimeter players (2:09 vs. 0:52 min:s; P < 0.001). Players performed 6.7 +/-
      3.5 repeated high-intensity activity bouts per match, suggesting that this facet
      of play is important in water polo. Overall, exercise intensity decreased as a
      match progressed, suggesting the likelihood of fatigue during the latter stages.
      These findings provide important information for the planning and monitoring of
      training in women's water polo.

PMID- 19847694
TI  - Toxis/hazardous substances and environmental engineering.

PMID- 19847695
TI  - Critical factors in chemical characterization for the evaluation of
      decontamination in solids using advanced oxidation.
AB  - Advanced oxidation technologies (AOT) have been applied to the treatment of
      numerous organic pollutants embedded in solid matrices (e.g., soil, sediments,
      sludge, etc.). Given potentially strong matrix-analyte interactions in solids,
      chemical characterization of both the target contaminants and their oxidation
      products is critical for the evaluation of any decontamination method. The
      success of AOT applications has been evaluated either directly (based on the
      removal of original contaminants, extent of mineralization, and/or formation of
      by-products), or indirectly, e.g., based on toxicity or chemical oxygen demand.
      Since indirect methods do not provide comprehensive understanding of the
      pollutants' fate, direct analytical approaches are covered in this review while
      focusing on sample preparation and detailed chromatographic characterization,
      assessing the strengths and weaknesses of these methods. The significance of
      sample preparation, in particular extraction, is discussed with respect to the
      nature of matrix-analyte interactions, as those may also affect the selection of
      the remediation method. The ultimate goal of this review is the presentation of
      methods employed to achieve mass balance closure, which is essential to ensure
      the full understanding of degradation pathways.

PMID- 19847696
TI  - Factors affecting microwave-enhanced advanced oxidation process for sewage sludge
      treatment.
AB  - The microwave-enhanced advanced oxidation process (MW/H(2)O(2)-AOP) was applied
      to sewage sludge for nutrient solubilization and solids' disintegration. Four
      factors, temperature, hydrogen peroxide dosage, mixing, and solids concentration
      were chosen for a screening experiment, and were ranked according to their
      significance of influence on the process. In general, temperature and hydrogen
      peroxide dosage are the two significant factors affecting the process, while
      mixing is the least significant factor. Temperature was the most significant
      factor for the release of orthophosphate, and hydrogen peroxide dosage was most
      important in ammonia release. Solids disintegration, in terms of soluble chemical
      oxygen demand (SCOD), was largely dependent on temperature and hydrogen peroxide
      dosage. For volatile fatty acids (VFA) release, mixing was the most significant
      factor. At higher temperatures with mixing, more VFA was released into the
      headspace, resulting in less VFA retained in the solution. The best results of
      solids' disintegration and nutrient release were obtained at 120 degrees C, and
      0.80 g H(2)O(2)/g dry sludge.

PMID- 19847697
TI  - Oxidation of PAHs in a simplified system using peroxy-acid and glass beads:
      Identification of oxidizing species.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are organic contaminants of concern due
      to their ubiquity, persistence in the natural environment and adverse health
      effects. Numerous studies have looked into the removal and treatment of these
      contaminants, with mixed results. High molecular weight PAHs have been
      particularly problematic due to their hydrophobicity and high affinity for
      organics, resulting in mass transfer limitations for even the fastest advanced
      oxidation processes (AOPs). The peroxy-acid process has been used to successfully
      treat PAH contaminated matrices. Experiments were conducted on benzo[a]pyrene
      contaminated glass beads in order to elucidate the reaction mechanisms
      responsible for the effectiveness of this process. For the first time peracetic
      acid (PAA) was identified as the important oxidant in this reaction. Different
      v/v/v ratios of hydrogen peroxide/acetic acid/DI water were studied which
      illustrated the importance of reaction ratio on oxidant concentration and rate of
      formation. Approximately 60% degradation of benzo[a]pyrene was achieved in 24
      hours with 1.7% PAA. Observations of the reaction kinetics suggest that the slow
      desorption/dissolution of benzo[a]pyrene limits the efficiency of the peroxy-acid
      process. Modifications of the reaction setup supported this observation as
      treatment efficiencies increased with reactive surface area, and an increase in
      system agitation. These limitations were also overcome by increasing the
      concentration of PAA delivered to the contaminated matrix. Greater than 80%
      degradation of benzo[a]pyrene was achieved in 24 hours with approximately 9.2%
      PAA.

PMID- 19847698
TI  - Oxidative degradation of 2,4,6-trichlorophenol and pentachlorophenol in
      contaminated soil suspensions using a supramolecular catalyst of 5,10,15,20
      tetrakis (p-hydroxyphenyl)porphine-iron(III) bound to humic acid via formaldehyde
      polycondensation.
AB  - A supramolecular catalyst consisting of 5,10,15,20-tetrakis(p
      hydroxyphenyl)porphine-iron(III) (FeTPP(OH)(4)) bound to humic acid (HA) was
      synthesized via formaldehyde polycondensation. The catalytic system, which
      included the synthesized catalyst (resol) and an oxygen donor (KHSO(5)), was
      applied to the oxidative degradation of 2,4,6-trichlorophenol (TrCP) and
      pentachlorophenol (PCP) in contaminated soil suspensions. The optimal conditions
      (catalyst, KHSO(5) and substrate concentrations) were investigated. In both
      FeTPP(OH)(4) and resol catalytic systems, more than 95% of TrCP (100 microM) and
      PCP (25 microM) degraded at pH 4, [catalyst] 20 microM and [KHSO(5)] 1 mM. When
      initial concentrations of TrCP and PCP were increased to [TrCP](0) 200 micro M
      and [PCP](0) 50 micro M, the percent degradation of the CPs and the levels of
      dechlorination in the resol catalytic system were significantly greater than the
      values obtained using the FeTPP(OH)(4) system. These results show that the
      synthesized resol catalyst effectively enhances oxidative degradation of TrCP and
      PCP in contaminated soil suspensions. The resol catalysts adsorbed to
      contaminated soils were at levels that were significantly greater than those of
      FeTPP(OH)(4). Therefore, the enhanced degradation of CPs by resol catalysts can
      be attributed to the interactions between adsorbed CPs on the soil surface and
      the catalytic center of the resol catalysts.

PMID- 19847699
TI  - Effect of sorption on contaminant oxidation in activated persulfate systems.
AB  - Sorption of hydrophobic contaminants to soils and subsurface solids is a
      significant limitation for the in situ chemical oxidation (ISCO) remediation of
      contaminated sites. A recently developed ISCO reagent, activated persulfate, was
      investigated for its potential to provide enhanced treatment of sorbed
      contaminants, a phenomenon that has previously been observed in catalyzed
      H(2)O(2) propagations (CHP; modified Fenton's reagent). Perchloroethylene (PCE)
      and hexachlorocyclopentadiene (HCCP) were sorbed to diatomaceous earth and
      treated with CHP, iron (II)-citrate-activated persulfate, and base-activated
      persulfate. Gas-purge desorption was used to measure the maximum natural rate of
      desorption of the compounds. Enhanced treatment of both sorbed probe compounds
      was observed in CHP reactions, with PCE and HCCP destruction occurring more
      rapidly than their respective rates of gas-purge desorption. However, probe
      compound loss in both formulations of activated persulfate was equal or less than
      the rates of gas-purge desorption, indicating that enhanced treatment of the
      sorbed contaminants did not occur in the persulfate reactions. Activated
      persulfate treatment is likely ineffective for hydrophobic compounds that are
      sorbed to soils and subsurface solids, and is probably more effective for
      compounds that are not limited by desorption.

PMID- 19847700
TI  - Influence of operational parameters on electro-Fenton degradation of organic
      pollutants from soil.
AB  - The combination of the Fenton's reagent with electrochemistry (the electro-Fenton
      process) represents an efficient method for wastewater treatment. This study
      describes the use of this process to clean soil or clay contaminated by organic
      compounds. Model soil of kaolinite clay polluted with the dye Lissamine Green B
      (LGB) was used to evaluate the capability of the electro-Fenton process. The
      effects of operating parameters such as electrode material and dye concentration
      were investigated. Operating in an electrochemical cell under optimized
      conditions while using electrodes of graphite, a constant potential difference of
      5 V, pH 3, 0.2 mM FeSO(4). 7H(2)O, and electrolyte 0.1 M Na(2)SO(4), around 80%
      of the LGB dye on kaolinite clay was decolorized after 3 hours with an electric
      power consumption around 0.15 W h g(-1). Furthermore, the efficiency of this
      process for the remediation of a real soil polluted with phenanthrene, a typical
      polycyclic aromatic hydrocarbon, has been demonstrated.

PMID- 19847701
TI  - Effect of H(2)SO(4) and HCl in the anode purging solution for the electrokinetic
      Fenton remediation of soil contaminated with phenanthrene.
AB  - The Electrokinetic-Fenton (EK-Fenton) process is a powerful technology to
      remediate organic-contaminated soil. The behavior of salts and acids introduced
      for the pH control has significant influence on the H(2)O(2) stabilization and
      destruction of organic contaminants. In this study, the effects of the type and
      concentration of acids, which were introduced at the anode, were investigated for
      the treatment of clayey soil contaminated with phenanthrene. In experiments with
      H(2)SO(4) as the anode solution, H(2)O(2) concentration in the anode reservoir
      decreased due to reaction between reduced species of sulfate and H(2)O(2), as
      time elapsed. By contrast, HCl as an electrolyte in the anode reservoir did not
      decrease the H(2)O(2) concentration in the anode reservoir. The reaction between
      the reduced species of sulfate and H(2)O(2) hindered the stabilization of
      H(2)O(2) in the soil and anode reservoir. In experiments with HCl for pH control,
      Cl(.), and Cl(2)(. -), which could be generated with mineral catalyzed Fenton
      like reaction, did not significantly hinder H(2)O(2) stabilization. H(2)O(2)
      transportation with electro-osmotic flow and mineral catalyzed Fenton-like
      reaction on the soil surface resulted in the simultaneous transport and
      degradation of phenanthrene, which are dependent of the advancement rate of the
      acid front and electro-osmotic flow toward the cathode according to HCl and
      H(2)SO(4) concentrations in the anode purging solution.

PMID- 19847702
TI  - Chemical degradation of PCB in the contaminated soils slurry: direct Fenton
      oxidation and desorption combined with the photo-Fenton process.
AB  - This paper reports the results of the direct treatment of PCBs sorbed to solid
      particles (glass beads and sand) employing the Fenton process. The results
      obtained with contaminated sandy soils show 98% removal of the original PCB
      structure and 82% dechlorination, all within a reaction time of 72 hours. The
      degree of removal was observed to be dependent on the level of congener
      chlorination. The optimized conditions were: 5% H(2)O(2); 100 ppm Fe(3+); sandy
      soil mass/volume of oxidizing solution ratio (m/V) of 1/3 g/mL, vigorous
      agitation and dispensed with the need for heat. Results obtained by applying an
      integrated desorption treatment followed by photo-Fenton oxidation to sandy soils
      contaminated with PCBs are also present in this paper. Desorption of PCBs with
      surfactant solutions took place to an extent of around 90% (92.2% with K
      perfluoroalkyl sulfonate, FT800, and 87% with Lineal Alkyl benzene Sulfonate,
      LAS), while photo-Fenton oxidation at 254 nm achieved degradation percentages
      close to 100% in 30 minutes for PCBs in solution, both with FT800 (98%) and LAS
      (97%) surfactants.

PMID- 19847703
TI  - Evaluation of a novel semi-solid Fenton process: case study on a kinetic model of
      o-nitroaniline degradation in hazardous solid waste.
AB  - A 'semi-solid' Fenton process (SSFP), in which the Fenton process (FP) takes
      place in a matrix with a low liquid-to-solid ratio (</= 5:1), was conducted on
      the degradation of o-nitroaniline (ONA) in hazardous solid waste. Based on the
      assumption of a first order reaction between ONA and the hydroxyl radical (.OH),
      an SSFP kinetic model was developed to accurately describe the kinetics of ONA
      degradation and to quantitatively investigate the effect of operating conditions.
      Half-life prediction model was also proposed and compared with the half-life
      calculated from pseudo first order equation to prove the effect of operating
      conditions. It showed that the degradation of ONA proceeded rapidly at pH 3.5.
      The kinetic rate constant, k, for ONA degradation increased with the initial
      ferrous ion concentration, but decreased with the liquid-to-solid ratio. With
      respect to the lowest residual ONA concentration, the optimal ferrous ion
      concentration and liquid-to-solid ratio were 0.062 mol/kg dry weight and 1.8,
      respectively.

PMID- 19847704
TI  - Remediation of Cu-contaminated soil using chelant and EAOP.
AB  - An electrochemical advanced oxidation process (EAOP) was used for treatment of
      the washing solution obtained during leaching of Cu (364 +/- 2 mg kg(-1))
      contaminated soil, with chelant S,S isomer of ethylenediamine disuccinate ([S,S]
      EDDS). In the EAOP (constant current density 40 mA cm(-2)), a boron-doped diamond
      anode was used for the generation of hydroxyl radicals and oxidative
      decomposition of [S,S]-EDDS-metal complexes in the washing solution. The released
      Cu was mostly electro-deposited on the stainless-steel cathode. Three consecutive
      additions of 5 mmol kg(-1) [S,S]-EDDS removed 46% of the Cu from the soil, mostly
      from carbonate and oxide soil fractions (87 and 99% Cu reduction). The soil Cu
      oral availability in the simulated stomach and intestinal phases (in vitro
      physiologically based extraction test) was reduced by 5.5 and 4.6-times. Cu plant
      availability (in vitro diethylenetriamine pentaacetate test) was reduced by 3.6
      times. The discharge solution was clear, almost colorless, with pH 8.4, 0.45 mg
      L(-1) Cu and 0.01 mM EDDS.

PMID- 19847705
TI  - Perfluoroalkyl sulfonic and carboxylic acids: a critical review of
      physicochemical properties, levels and patterns in waters and wastewaters, and
      treatment methods.
AB  - Perfluorinated acids (PFAs) are an emerging class of environmental contaminants
      present in various environmental and biological matrices. Two major PFA
      subclasses are the perfluorinated sulfonic acids (PFSAs) and carboxylic acids
      (PFCAs). The physicochemical properties and partitioning behavior for the linear
      PFA members are poorly understood and widely debated. Even less is known about
      the numerous branched congeners with varying perfluoroalkyl chain lengths,
      leading to confounding issues around attempts to constrain the properties of
      PFAs. Current computational methods are not adequate for reliable multimedia
      modeling efforts and risk assessments. These compounds are widely present in
      surface, ground, marine, and drinking waters at concentrations that vary from pg
      L(-1) to microg L(-1). Concentration gradients of up to several orders of
      magnitude are observed in all types of aquatic systems and reflect proximity to
      known industrial sources concentrated near populated regions. Some wastewaters
      contain PFAs at mg L(-1) to low g L(-1) levels, or up to 10 orders of magnitude
      higher than present in more pristine receiving waters. With the exception of
      trifluoroacetic acid, which is thought to have both significant natural and
      anthropogenic sources, all PFSAs and PFCAs are believed to arise from human
      activities. Filtration and sorption technologies offer the most promising
      existing removal methods for PFAs in aqueous waste streams, although sonochemical
      approaches hold promise. Additional studies need to be conducted to better define
      opportunities from evaporative, extractive, thermal, advanced oxidative, direct
      and catalyzed photochemical, reductive, and biodegradation methods. Most PFA
      treatment methods exhibit slow kinetic profiles, hindering their direct
      application in conventional low hydraulic residence time systems.

PMID- 19847706
TI  - A blood lead benchmark for assessing risks from childhood lead exposure.
AB  - Lead exposure is an insidious problem, causing subtle effects in children at low
      exposure levels where clinical signs are not apparent. Although a target blood
      lead concentration (Pb(B)) of ten micrograms per deciliter (10 microg/dL) has
      been used as the basis for environmental decision-making in California for nearly
      two decades, recent epidemiologic evidence suggests a relationship between
      cognitive deficits and Pb(B) at concentrations < 10 microg/dL. Based on a
      published meta-analysis of children's IQ scores and their blood lead
      concentrations, we developed a new blood lead benchmark: an incremental increase
      in blood lead concentration (DeltaPb(B)) of 1 microg/dL, an increase that we
      estimate could decrease the IQ score in an average school child in California by
      up to one point. Although there is no evidence to date for a threshold for the
      neurobehavioral effects of lead, a one-point IQ decrement was chosen to represent
      a de minimus change. To safeguard the intellectual potential of all children,
      additional efforts to reduce or eliminate multiple-source exposures to lead are
      warranted.

PMID- 19847707
TI  - Degradation of chlorinated butenes and butadienes in granular iron columns.
AB  - Manufacturing facilities for production of chlorobutyl rubber have the potential
      to release a mixture of at least 5 chlorinated butenes and butadienes including
      trans-1,4-dichlorobutene-2 (1,4-DCB-2), 3,4-dichlorobutene-1 (3,4-DCB-1), 2,3,4
      trichlorobutene-1 (TCB), 2-chlorobutadiene-1,3 (chloroprene) and 2,3
      dichlorobutadiene-1,3 (DCBD) into groundwater environment. To evaluate the
      potential of using granular iron in the remediation of the above contaminants, a
      series of column experiments were conducted. Degradation of all 5 compounds
      followed pseudo-first-order kinetics. The three chlorinated butenes degraded much
      faster (surface area normalized half-lives, t(1/2)', ranged from 1.6 to 5.2 min
      m2/mL) than the 2 chlorinated butadienes (t(1/2)' ranged from 102 to 197 min
      m2/mL). All contaminants fully dechlorinated by granular iron to 1,3-butadiene as
      a common reaction intermediate that then degraded to a mixture of relatively non
      harmful end products consisting of 1-butene, cis-2-butene, trans-2-butene and n
      butane. Based on the kinetic data, product distributions, and chlorine mass
      balances, reaction pathways for these compounds are proposed. For the chlorinated
      butenes, 3,4-DCB-1 and TCB, undergo reductive beta-elimination reactions
      resulting in 1,3-butadiene and chloroprene intermediates. Dechlorination of 1,4
      DCB-2 to 1,3-butadiene occurs through a reductive elimination similar to
      reductive beta-elimination. For dechlorination of the two chlorinated butadienes,
      chloroprene and DCBD, dechlorination occurs through a hydrogenolysis pathway. The
      common non-chlorinated intermediate, 1,3-butadiene, undergoes catalytic
      hydrogenation resulting in a mixture of butane isomers and n-butane. The results
      suggest that granular iron is an effective material for treatment of groundwater
      contaminated with these compounds.

PMID- 19847708
TI  - A principal components analysis of the factors effecting personal exposure to air
      pollution in urban commuters in Dublin, Ireland.
AB  - Principal component analysis was used to examine air pollution personal exposure
      data of four urban commuter transport modes for their interrelationships between
      pollutants and relationships with traffic and meteorological data. Air quality
      samples of PM2.5 and VOCs were recorded during peak traffic congestion for the
      car, bus, cyclist and pedestrian between January 2005 and June 2006 on a busy
      route in Dublin, Ireland. In total, 200 personal exposure samples were recorded
      each comprising 17 variables describing the personal exposure concentrations,
      meteorological conditions and traffic conditions. The data reduction technique,
      principal component analysis (PCA), was used to create weighted linear
      combinations of the data and these were subsequently examined for
      interrelationships between the many variables recorded. The results of the PCA
      found that personal exposure concentrations in non-motorised forms of transport
      were influenced to a higher degree by wind speed, whereas personal exposure
      concentrations in motorised forms of transport were influenced to a higher degree
      by traffic congestion. The findings of the investigation show that the most
      effective mechanisms of personal exposure reduction differ between motorised and
      non-motorised modes of commuter transport.

PMID- 19847709
TI  - Indoor air quality in university classrooms and relative environment in terms of
      mass concentrations of particulate matter.
AB  - The mass concentrations of coarse (PM10) and fine (PM2.5) particulate matter were
      measured in different classrooms and relevant indoors areas of Democritus
      University, School of Engineering, Xanthi, with portable aerosol monitoring
      equipment. Two sampling campaigns were conducted in different seasons. The
      results indicated that the average concentrations in classrooms ranged from 32
      188 microg/m3 and 25-151 microg/m3 for PM10 and PM2.5, respectively.
      Concentration levels above 300 microg/m3 were usually recorded, while the
      PM2.5/PM10 ratio was about 0.8. As expected, PM10 and PM2.5 average
      concentrations were significantly higher in the open-access meeting place of
      common use, indicating the significance of student trespassing and occasional
      smoking in the deterioration of indoors air quality.

PMID- 19847710
TI  - Solventless sampling of phthalate esters.
AB  - An environmentally friendly method to passively sample six phthalate esters in
      water has been devised. The sampling device consists of a semi-permeable
      membrane, which the analytes diffuse through and are collected onto Tenax TA. The
      Tenax TA was then thermally desorbed with a helium stream into a gas
      chromatograph-mass spectrometer (GC-MS) after the sampling period. Samplers were
      exposed to water samples for known periods of time at known concentrations to
      create time-weighted average (TWA) plots. For all six phthalates the resulting
      TWA plots had linear correlations, allowing for the determination of permeation
      constants for the phthalates. The lag time for each phthalate was also determined
      using this method. An advantage of this method is that no solvents are used. The
      analytes are removed from the Tenax TA using thermal desorption rather than
      liquid extraction.

PMID- 19847711
TI  - Occurrence and distribution of polycyclic aromatic hydrocarbons in the Egyptian
      aquatic environment.
AB  - Persistent organic pollutants (POPs) such as polycyclic aromatic hydrocarbons
      (PAHs) are of great concern due to their persistence, bioaccumulation and toxic
      effects. In this study, water samples were collected during 2007-2008 from two
      catchment areas that represent two different models of the aquatic environment in
      Egypt (Rosetta branch as fresh water and El-Moheet drain as untreated/treated
      waste water). The distribution of 16 PAHs included in the US Environmental
      Protection Agency's (EPA) priority pollutant list was analyzed by gas
      chromatography/mass spectrometry (GC/MS). Total PAH concentrations varied from
      242 to 732 ng/L in fresh water from the Rosetta branch with a mean value of 408
      ng/L; and for waste water the concentrations were in the range 894 to 1979 ng/L
      with a mean value of 1476 ng/L. The PAH profiles were dominated by low molecular
      weight PAHs (two- and three-ring components) in all collected water samples. The
      origin of PAHs in both waste water and fresh water in these study areas may be
      from oil or sewage contamination. The total PAHs concentrations of untreated
      waste water decreased along the treatment process by about 30% at the Zenein
      waste water treatment plant. The levels of PAHs in waste water are relatively
      high, although lower than locations with known problems.

PMID- 19847712
TI  - Variation, correlation, and toxicity of phenolic endocrine-disrupting compounds
      in surface water.
AB  - This study investigated the variation in toxicity of phenolic endocrine
      disrupting compounds (EDCs) and determined the correlation between their
      concentrations. All twenty-four samples acquired from a polluted river contained
      five phenolic EDCs. The EDC nonylphenol (NP) concentration was found to be the
      highest (4.26 +/- 2.74 microg/L) in the river water. In addition the
      concentrations of nonylphenol diethoxylate, (NP2EO), octylphenol (OP),
      nonylphenol monoethoxylate (NP1EO), and bisphenol A (BPA) were 1.58 +/- 1.37
      microg/L; 2.90 +/- 2.77 microg/L; 2.89 +/- 2.15 microg/L; and 2.25 +/- 0.96
      microg/L, respectively. Concentrations of NP, NP1EO, and OP were significantly
      greater in the daytime than in the nighttime samples. Furthermore, concentrations
      of NP, NP1EO, and NP2EO showed a strong correlation due to similar parent
      compounds while BPA and OP did not. NP1EO had the highest risk to aquatic
      organisms (hazard quotient, HQ = 26.3) and BPA the lowest (HQ = 2.24).The
      accumulative HQ sum (hazard index, HI) was 81.3 within all the samples. The HI
      was 110.3 in the daytime samples. This was 97% higher than in the nighttime HI
      (56.3), which suggested daytime anthropogenic discharges were an important source
      of toxicity to aquatic organisms.

PMID- 19847713
TI  - Corrosion control in water supply systems: effect of pH, alkalinity, and
      orthophosphate on lead and copper leaching from brass plumbing.
AB  - This study explored the potential of lead and copper leaching from brass plumbing
      in the Auckland region of New Zealand. A five-month field investigation, at six
      representative locations, indicated that Auckland's water can be characterized as
      soft and potentially corrosive, having low alkalinity and hardness levels and a
      moderately alkaline pH. More than 90% of the unflushed samples contained lead
      above the maximum acceptable value (MAV) of 10 microg/L (New Zealand Standards).
      In contrast, the copper level of unflushed samples remained consistently below
      the corresponding MAV of 2 mg/L. Flushing however reduced sharply metal
      concentrations, with lead values well below the MAV limit. Generally, metal
      leaching patterns showed a limited degree of correlation with the variations in
      temperature, dissolved oxygen and free chlorine residual at all sampling
      locations. Furthermore, a series of bench-scale experiments was conducted to
      evaluate the effectiveness of pH and alkalinity adjustment, as well as
      orthophosphate addition as corrosion control tools regarding lead and copper
      dissolution. Results demonstrated that lead and copper leaching was predominant
      during the first 24 hr of stagnation, but reached an equilibrium state
      afterwards. Since the soluble fraction of both metals was small (12% for lead,
      29% for copper), it is apparent that the non-soluble compounds play a predominant
      role in the dissolution process. The degree of leaching however was largely
      affected by the variations in pH and alkalinity. At pH around neutrality, an
      increase in alkalinity promoted metal dissolution, while at pH 9.0 the effect of
      alkalinity on leaching was marginal. Lastly, addition of orthophosphate as a
      corrosion inhibitor was more effective at pH 7.5 or higher, resulting in
      approximately 70% reduction in both lead and copper concentrations.

PMID- 19847714
TI  - Irrigation with treated wastewater: effects on soil, lettuce (Lactuca sativa L.)
      crop and dynamics of microorganisms.
AB  - The aim of this study was to evaluate the applicability of treated wastewater for
      horticultural crops, assess the effects of continuous use of treated water on
      soil and crops, and analyse the physical, chemical and biological effects of
      irrigation with recycled water. Two lettuce plots watered with drinking water and
      treated wastewater were monitored over a three year period. Nutrients, heavy
      metal and the dynamics of pathogen and indicator microorganism content in soil
      and foliar tissues were analysed. Wastewater irrigation had a high influence on
      soil parameters: organic matter, N, P, Ca, Al, Fe, Pb and Zn. Indicator and
      pathogenic microorganisms were detected in soil and plants grown in the
      wastewater-irrigated plot, and persisted in the soil for 27 days during the study
      under humid conditions. N, P, Pb and Al content were significantly higher in
      plant tissues of wastewater-irrigated plots than in the control after 3 years of
      irrigation. Harvest was significantly higher in the wastewater-irrigated plot.
      Wastewater can be a resource for agricultural irrigation. In any case, the
      possible heavy metal accumulation in soils and presence of pathogenic organisms
      require careful management of this alternative resource: use of a drip irrigation
      system, previous wastewater disinfection and a limited irrigation period are
      recommended.

PMID- 19847715
TI  - Electrothermal atomic absorption spectrometric determination of cadmium and lead
      in traces in aquatic systems following flotation by two chromium(III) collectors.
AB  - A fast flotation method for determination of cadmium and lead in aquatic systems
      by two chromium(III) collectors is described. The first collector is a colloid
      precipitate of hydrated chromium(III) oxide, Cr2O3 x xH2O, while the second is a
      bulk chromium(III) pentamethylenedithiocarbamate, Cr(PMDTC)3. Cadmium and lead
      present in water are incorporated into the collector mass at pH 7.5 by addition
      of 20 mg of Cr(III) and 0.4 mmol of pentamethyleneammonium
      pentamethylenedithiocarbamate, PMA-PMDTC, to 0.5 L water sample. A solid
      precipitate was separated from the processed water system by air bubbles. After
      dissolving with strong acid, the solution is tested by electrothermal atomic
      absorption spectrometry (ETAAS). The limit of detection for Cd by flotation/ETAAS
      method is 0.002 microg L(-1), while for Pb is 0.04 microg L(-1). The precision of
      the method is expressed as relative standard deviations ranging of 5.0% for Cd
      (concentration range from 0.1 to 0.5 microg L(-1)) and 4.25% for Pb
      (concentration range from 0.5 to 5 microg L(-1)). The characteristic mass (mass
      that gives an integrated absorbance of 0.0044 s) of 1.06 pg for Cd and 16.7 pg
      for Pb were obtained. The method was validated by the standard additions and by
      its application to the reference materials (Surface water-SPS-SW-1, River Thames
      Water-LGC-6019).

PMID- 19847716
TI  - The bulk composition and leaching properties of electroplating sludge
      prior/following the solidification/stabilization by calcium oxide.
AB  - Eighteen samples of electroplating sludge were taken from three vertical profiles
      of waste storage pond of the zinc plating facility. Dry matter and organic matter
      content, pH value, bulk concentrations and leachate composition were determined.
      A sludge sample with the highest zinc value in the leachate was treated with
      calcium oxide (10% to 70%) and the obtained solidificate was repeatedly tested.
      There were found significant variations of all measured parameters among the
      profiles of untreated waste. Dry matter content varied from 125 to 455 mgg(-1),
      organic matter varied from 94.3 to 293.9 mgg(-1), and pH value varied from 3.42
      to 5.90 (mean 4.34). Iron content ranged from 38.4 to 191.4 mgg(-1) (mean 136
      mgg(-1); RSD 0.25), while zinc ranged from 10.9 to 58.2 mgg(-1) (mean 33.4 mgg(
      1); RSD 0.38). According to its DIN38414-S4 leachate composition, this material
      was not suitable for landfilling of inert waste since zinc and nickel mean values
      were 10 and 1.5 times higher, respectively, and maximum values 27 and 2.5 times
      higher, respectively, compared to the upper permissible limit. Maximum values of
      Cr(VI), Fe, Ni, Cu, and Zn in the DIN38414-S4 leachate were 0.183 mgL(-1), 34.085
      mgL(-1), 1.052 mgL(-1), 0.829 mgL(-1) and 107.475 mgL(-1)L, respectively.
      Following the solidification/stabilization procedure with CaO (sample/CaO =
      90/10), concentrations of Cr(VI), Fe, Cu and Zn were reduced 92, 44, 66 and 57
      times, respectively, compared to the untreated sample. The addition of 50% of CaO
      into the sludge reduced zinc and nickel concentrations 79 and 45 times,
      respectively, in the DIN38414-S4 leachate of the solidified waste compared to the
      original sludge, thereby converting an hazardous waste into the inert material
      suitable for landfilling or reuse in the construction processes.

PMID- 19847717
TI  - Performance of COD removal from oxide chemical mechanical polishing wastewater
      using iron electrocoagulation.
AB  - This study investigated the feasibility of chemical oxygen demand (COD) abatement
      from oxide chemical mechanical polishing (oxide-CMP) wastewater. The process
      variables, including applied voltage, electrolyte concentration and temperature,
      were evaluated in terms of COD removal efficiency. In addition, the effects of
      applied voltage, supporting electrolyte, and temperature on electric energy
      consumption were evaluated. Under the optimum balance of variables, satisfactory
      COD removal efficiency and relatively low energy consumption were achieved. The
      optimum electrolyte concentration, applied voltage, and temperature were found to
      be 200 mg/L NaCl, 20 V, and 25 degrees C, respectively. Under these conditions,
      the COD concentration in oxide-CMP wastewater decreased by more than 90%,
      resulting a final wastewater COD concentration that was below the Taiwan
      discharge standard (100 mg/L). Since the processed wastewater quality exceeded
      the direct discharge standard, the effluent could be considered for reuse. COD
      removal rates obtained during the electrocoagulation process can be described
      using a pseudo-kinetic model. The present study results show that the kinetic
      data fit the pseudo first-order kinetic model well. Finally, the morphology and
      composition of the sludge produced were characterized using scanning electron
      microscopy (SEM) and energy dispersion spectra (EDS).

PMID- 19847718
TI  - Effect of temperature over start-up of a groundwater-denitrifying submerged
      filter inoculated with psychrotolerant bacteria.
AB  - Inoculation of a submerged filter was carried out using three bacterial strains
      previously selected on the basis of their psychrotolerance and high denitrifying
      activity with the aim of apply selective inoculation to a submerged filter system
      for the denitrification of groundwater. Laboratory-scale assays were carried out
      at 5, 10 20 and 30 degrees C. Surface scanning microscopy was used to evaluate
      the capacity of each inoculant to colonise the support. In all cases a biofilm in
      the initial stages of development was observed, with abundant connection material
      and cells in division. Increase in temperature had a negative effect on
      colonisation evolution, motivated by the use of psychrotolerant bacteria. Each
      inoculant presented a different colonisation optimum, but always at temperatures
      under 20 degrees C. To monitor system setup, concentrations of total nitrogen,
      nitrate and nitrite after treatment were measured. In most cases, the
      stabilisation phase was observed to be longer at lower temperatures,
      independently of the inoculant employed. However, at 5 degrees C, only one of the
      inoculants reached steady-state phase with total nitrogen elimination. In all the
      assays, an accumulation of nitrite was observed during stabilisation phase. At
      lower temperatures, maximum concentrations of nitrite were greater and were
      reached after longer operation times. Use of selective inoculants was shown to
      promote subsequent development of a stable biofilm achieving efficient
      elimination of nitrate from the influent. This occurs regardless of the inoculant
      employed, except at a temperature of 5 degrees C, at which the type of inoculant
      conditions system setup. However, colonisation capacity of the inoculant at low
      temperatures is not a determining factor.

PMID- 19847719
TI  - Development and optimization of a culture medium for L-lactic acid production by
      Rhizopus oryzae using crude protein from dairy manure as a nitrogen source.
AB  - Experiments were conducted using the crude protein in fresh dairy manure as the
      nitrogen source in the culture media for Rhizopus oryzae to produce L-lactic
      acid. Two uniform design experiments were carried out with one for optimizing
      seed culture while the other for best percent L-lactic acid production. Multiple
      linear regression and ANOVA analyses were employed to determine the most
      significant media components. Data from the first uniform design U6 (6(2)x 3), in
      which the experimental factors involved included nitrogen concentration (crude
      protein), spore concentration, and treatment duration, showed that the levels of
      these components in the optimal condition for the seed culture medium were 2.1
      g/L nitrogen, 16 hour culture time, and 10(5) spore concentration. The biomass
      weight in the seed medium developed in this study reached 1.32 g/L, which was
      48.3% higher than that of the control. The combination of culture time and
      nitrogen concentration was found to be most significant in influencing the
      biomass yield. In the second uniform design experiment, flask culture with five
      factors (glucose, nitrogen from dairy manure, ZnSO4, KH2PO4, and MgSO4) at eight
      levels was examined using the uniform design table U8 (8(5)) with the content of
      L-lactic acid as the evaluating response Y. The results showed that ZnSO4 had the
      most influence on L-lactic acid yield, followed by nitrogen and KH2PO4. The
      optimum culture medium in terms of lactic acid production consisted of 240 g/L
      glucose, 1.26 g/L crude protein, 1.05 g/L KH2PO4, and 0.25 g/L MnSO4, which could
      achieve a yield of 59.57% (7.1% higher than the control).

PMID- 19847720
TI  - [Psychosomatic rehabilitation: quo vadis?].
AB  - According to the latest research its effectiveness can be considered as proven.
      By now there are many evaluation studies that document the psychosomatic
      rehabilitation process itself as well as long-term results. In the wake of
      procedural optimization in medical rehabilitation, however, potential for further
      development has also been stated, in particular given an increasing number of
      psychosomatic patients and their heterogeneous disease patterns. Hence, an
      increasing number of studies has been carried out over the last ten years which
      had been aimed at achieving a match between patients' needs and rehabilitation
      offers (therapy, patient-education). This survey gives an overview of recent
      studies on the effectiveness of psychosomatic rehabilitation and discusses new
      concepts for further optimization.

PMID- 19847721
TI  - [Stance toward psychosomatic rehabilitation: development of a patient
      questionnaire].
AB  - BACKGROUND: The transition from home to psychosomatic rehabilitation is
      problematic for many patients. They show little treatment motivation because of
      insufficient information and fear of stigmatization. Pre-treatment seeks to
      reduce these problems. The patient-questionnaire for stance toward psychosomatic
      rehabilitation was developed and tested for performance criteria. METHODS: A
      German statutory pension insurance scheme sample of psychosomatic rehabilitation
      patients (n=317) were recruited for testing psychosometric attributes and were
      questioned before and after pre-treatment. To determine whether the questionnaire
      can show clinically relevant changes, 124 patients with pre-information were
      compared with 88 patients without intervention. Additionally, clinically relevant
      changes for patients without knowledge of psychosomatic rehabilitation (n=70)
      were analyzed. RESULTS AND CONCLUSIONS: Factor analysis shows a three factor
      solution with ten items. The discriminatory power was good. High reliability was
      found for two factors and lower reliability for one factor. The patient
      questionnaire for stance toward psychosomatic rehabilitation contains three
      scales: "knowledge", "confidence", and "motivation", and can be characterized as
      a reliable and economic instrument. After pre-treatment a general improvement was
      observed regarding patients' stance toward psychosomatic rehabilitation. The
      analyses result in significantly higher mean for patients with pre-treatment.
      Patients without previous information showed less "confidence" and "motivation".
      Pre-treatment can have a positive impact on the stance toward psychosomatic
      rehabilitation.

PMID- 19847722
TI  - [Can quality of life in psychotherapy be measured with clinician-ratings? A
      comparison of patient- and clinician-ratings using the SF-8].
AB  - OBJECTIVE: Quality of life is a major criterion of the outcome of
      psychotherapeutic interventions. The concept of quality of life emphasizes
      patient self-ratings. However, they can be burdensome or inappropriate in some
      cases. Therefore we have compared self-ratings and clinician-ratings of quality
      of life. METHODS: Self- and clinician-ratings of the SF-8 (1-week recall version)
      were measured from consecutive samples of 1 812 inpatients from eleven
      psychotherapeutic clinics at admission and at discharge six weeks later. A
      physical summary score (PSS) and a mental summary score (MSS) were calculated.
      Pearson product-moment correlations were used. RESULTS: Self- and clinician
      ratings of the PSS correlate r=0.48 at admission and r=0.58 at discharge, of the
      MSS r=0.46 and r=0.51, respectively. Concerning single items we find the highest
      correlation for item 4 (bodily pain: r=0.53 and r=0.55), the lowest for item 6
      (social functioning: r=0.26 and r=0.30). Change scores of the PSS correlate
      r=0.20, of the MSS r=0.32. Correlations differ between diagnostic groups:
      Correlations are low for patients with either schizophrenia (F2), depressive
      episode (F32) or personality disorder (F60-62), comparatively higher for patients
      with dysthymia. Comparing correlations across the 11 clinics reveals substantial
      differences, for the MSS ranging from r=0.38 to r=0.58 at admission and r=0.27 to
      r=0.68 at discharge. CONCLUSION: Patient self-ratings of quality of life as a
      psychotherapeutic outcome measure using the SF-8 Health Survey could not be
      substituted by clinician-ratings, they should be used as complements.

PMID- 19847723
TI  - [Measuring positive behaviour and experience in inpatients with mental disorders-
      the Hamburg Self-Care Questionnaire (HamSCQ)].
AB  - OBJECTIVES: Treatments of patients with chronic mental disorders are increasingly
      focusing on salutogenetic aims to support human health and well-being. Up to now,
      standardized instruments to evaluate these treatment goals are still missing. We
      present results of analyses of the psychometric properties of the Hamburg Self
      Care Questionnaire (HamSCQ). Besides reliability we are focusing on different
      aspects of validity: factor structure, concurrent validity, and sensitivity to
      change. METHODS: A total sample of 7 478 inpatients with mental disorders from
      four different psychotherapeutic clinics participated in the study. Patients
      completed self-rating questionnaires at admission and discharge: Besides the
      HamSCQ we used the Symptom Checklist SCL-14, the Short Form SF-8, the CES-D
      depression scale, the Inventory of Interpersonal Problems IIP-25 and the AVEM.
      RESULTS: The two-dimensional structure of the HamSCQ with the two subscales
      PACING and POSITIVE EXPERIENCE could be replicated by means of both principal
      component and confirmatory factor analysis. The two scales correlate with r=0.56.
      Both scales show a high internal consistency (alpha >or=0.90), they correlate
      with the selected measures of concurrent validity (except the AVEM scales) with
      medium (Pacing) or high (Positive Experience) effect sizes, and their mean scores
      differ significantly from admission to discharge with large effect sizes.
      CONCLUSIONS: The HamSCQ proves to be a reliable questionnaire, which is also
      sensitive to change. The two-dimensional factor structure could be replicated,
      and some aspects of concurrent validity could be demonstrated, but concerning
      criterion validity further research is still necessary. Thus we recommend the use
      of the HamSCQ for inpatients with mental disorders treated in
      psychotherapeutic/rehabilitative clinics.

PMID- 19847724
TI  - [Psychosomatic rehabilitation: effects of pre-treatment counselling under the
      statutory pension insurance scheme].
AB  - BACKGROUND: Currently, little is known about the influence of pre-treatment in
      rehabilitation outcomes of patients with psychosomatic symptoms. This study
      examines whether there are differences in therapy motivation and impairment
      between patients with and those without pre-treatment measures. Additionally, the
      outcome for patients with prior knowledge of psychosomatic rehabilitation is
      analyzed. METHODS: As part of a randomized controlled pre-post design the
      Patients' questionnaire of therapy motivation (PAREMO) and the Brief Symptom
      Inventory (BSI) were distributed to 166 patients in psychosomatic rehabilitation.
      The selection of patients with prior knowledge of psychosomatic rehabilitation
      was made according to the scale "knowledge" of the patients' questionnaire.
      Changes were tested by analysis of variance at two treatment points. RESULTS:
      Although there were positive effects of rehabilitation, no interaction was found
      between measurement points and groups. The analyses of patients without prior
      knowledge of psychosomatic rehabilitation showed different outcomes for males and
      females. Higher rehabilitation outcomes for females than for males were found on
      the BSI scales "somatisation", "phobic anxiety", and "psychoticism". CONCLUSIONS:
      The findings show that pre-treatment facilitates the patients' approach to
      psychosomatic rehabilitation. Apart from receiving information patients should be
      motivated more strongly and their confidence in psychosomatic rehabilitation
      strengthened.

PMID- 19847725
TI  - [Patients with chronic low back pain: the impact of psychosocial features].
AB  - BACKGROUND: Chronic low back pain (CLBP) is often associated with clinical and
      subclinical levels of psychological problems. A higher stage of chronicity is
      associated with an increase in co-existing psychological disorders. Previous
      programmes of inpatient orthopaedic rehabilitation reveal little evidence of
      sustained rehabilitation effects, a finding which may be attributable to the
      absence of specific psychological treatment during the programme. PURPOSE: Does
      cognitive-behavioural depression management training in patients with CLBP and
      depressive symptoms improve the inpatient orthopaedic rehabilitation success
      depending on the stage of chronicity? METHOD: Effects of the new programme on
      psychological well-being (ADS depressive symptoms, HADS anxiety, SCL somatization
      and mental health of the SF-12) were investigated in n=75 patients with first and
      second stage of chronicity immediately after, six months after and 24 months
      after rehabilitation and were compared to standard rehabilitation without
      management of depressive symptoms. RESULTS: All patients benefited from both
      treatments immediately after rehabilitation. However, six months after
      rehabilitation only patients of the intervention group showed significant
      beneficial effects with regard to depressive symptoms and mental health. The
      lowered depressive symptoms remained stable up to the 24-month follow-up
      assessment. Anxiety in the second stage of chronicity was reduced up to the 6
      month follow-up and in the first stage up to the 24-month follow-up. CONCLUSIONS:
      The new programme with a cognitive-behavioural depression management training
      revealed beneficial effects on mental health in the mid-term and on depressive
      symptoms in the long-term. However, the effects need to be further improved by
      after-care programmes.

PMID- 19847726
TI  - [Fibromyalgia: influence of depressive symptoms on the outcome after
      rehabilitation].
AB  - BACKGROUND: For the therapy of fibromyalgia a multimodal therapy with patient
      education is recommended. It integrates pain management and stress management as
      well as cognitive restructuring. It will be examined whether depressiveness has
      an influence on rehabilitation outcome immediately after inpatient
      rehabilitation. METHODS: Various questionnaires, i. e. the Hospital Anxiety and
      Depression Scale (HADS-D), German Pain Questionnaire (DSF), Cognitive,
      Behavioural Coping and Psychological Strains Through Chronic Pain questionnaire
      (FESV), German version of the Pain Anxiety Symptom Scale (PASS-D) and the Patient
      questionnaire IRES-24, were distributed to 102 fibromyalgia patients in the
      framework of a pre post design. The scores of patients with and without
      depressiveness (HADS-D cut-off >or=11) were compared by analysis of variance at
      two treatment points. RESULTS AND CONCLUSIONS: Immediately after therapy, a
      general improvement was found regarding depressiveness and pain (strong effect
      size) as well as regarding pain-related anxiety (medium effect sizes). Only
      "countertraded activity" of coping with pain did not show any improvement. The
      "rehabilitation status" improved significantly whereas, in contrast, the
      "physical health" aspect did not improve. A significant increase was found on the
      "pain" scale. Additionally, depressive symptoms had a strong impact on the
      aspects "physical health", "subjective health" and on "rehabilitation status". In
      particular, patients with fibromyalgia and depressiveness showed poorer outcomes
      regarding these aspects than patients with fibromyalgia without depressiveness. A
      multimodal therapy with patient education can have a positive impact on the
      outcome of rehabilitation.

PMID- 19847727
TI  - [Fibromyalgia: influence of depressive symptoms in coping with pain].
AB  - BACKGROUND: The aim of this study was to investigate how depressiveness affects
      coping of patients with fibromyalgia. It was assumed that depressiveness has an
      influence on coping, self-efficacy und motivation for therapy. METHODS: A total
      of 251 patients with fibromyalgia. The investigation started at the outset of
      their stay in the clinic, and both patients with and without depressiveness (HADS
      D cut-off >or=11) were examined. To investigate the differences, multivariate
      variance models were used for cognitive and behavioural coping, self-efficacy and
      motivation for therapy. Data were collected using the Hospital Anxiety and
      Depression Scale (HADS-D), German pain questionnaire (DSF), Questionnaire for
      assessment of level of coping with pain (FESV) and the German version of the Pain
      stages of change questionnaires (FF-STABS). RESULTS AND CONCLUSIONS: Comparison
      of the groups shows significantly lower means for the fibromyalgia patients with
      depressive symptoms concerning "perceived self-competence", "cognitive
      restructuring", and "countertraded activity". The same results can be observed
      for "self-efficacy". Analysis of the motivation for therapy in the "carefreeness"
      scale shows significantly higher means in the fibromyalgia patients with
      depressive symptoms. In the "maintenance" scale, however, lower means are
      observed in this patient group. As fibromyalgia patients with depressive symptoms
      show greater strain on account of their psychosomatic symptoms, depressive
      symptoms should be dealt with during treatment.

PMID- 19847728
TI  - [Are harassment victims a special group of patients in psychosomatic
      rehabilitation?].
AB  - BACKGROUND: Between 50 and 90% of patients in psychosomatic rehabilitation are
      affected by occupational problems and misdirected stress. The patients often find
      themselves in a vicious circle in which occupational problems lead to the
      development of mental illnesses before a background of lacking compensation
      possibilities and positive resources. Besides, mobbing can be understood as a
      special form of occupational stress, whereas in former studies, no differences in
      the magnitude of mental strain were discovered in comparison with rehabilitants
      who were in a psychosomatic remedial treatment. PURPOSE: Patients who are in
      psychosomatic remedial treatment and are norm-aberrantly limited in their
      occupational efficiency and patients who are affected by mobbing in the job show
      a higher psychosocial strain than other patients in treatment whose occupational
      efficiency is not limited. Do mobbing victims more frequently receive a
      recommendation that measures to strengthen their working life participation be
      considered? METHOD: A total of 189 patients were handed out a questionnaire at
      the beginning of their remedial treatment comprised of questions regarding their
      mobbing experiences, the IRES-3, the SCL-27, the Fatigue-Scale, the Incongruity
      questionnaire and the VDS-scale. The sample was split up into a group whose
      occupational efficiency was limited, a group affected by mobbing, and a group who
      had no efficiency limitations. RESULTS: 72.6% were clearly limited in their
      occupational efficiency. 27.4% felt neither affected in their occupational
      efficiency nor due to mobbing. 21% of the sample as a whole were affected by
      mobbing. Patients limited in their occupational efficiency differed neither from
      patients whose efficiency was unlimited, nor from those who were affected by
      mobbing. On the other hand, mobbing victims differed in all symptom scales
      evaluated from patients who had no occupational efficiency limitations. Also the
      scales on personality styles were substantially increased compared to this group.
      With mobbing victims it was recommended more often that the possibilities for
      working life participation measures should be checked. CONCLUSIONS: Patients in
      psychosomatic rehabilitation are strongly affected by occupational limitations
      and have a huge need for counselling and support. Therapy concepts should pick up
      the occupational problems at hand in a differentiated manner, with job-oriented
      linked-up rehabilitation being recommended. The increased mental strain of
      mobbing victims must always be borne in mind.

PMID- 19847729
TI  - [Scientific expert group RehaFutur].

PMID- 19847730
TI  - [Quality management: protocols for reporting in-hospital emergencies. Comparison
      of two methods].
AB  - BACKGROUND AND OBJECTIVE: 10-20% of hospitalized patients experience adverse
      events, becoming clinically relevant in emergency situations (ES). Many studies
      have confirmed deficits in both organizational and professional aspects of care
      when responding to acute illness. These may result in a worsening outcome. A
      detailed reporting of acute intervention is necessary to make possible the
      detailed analysis of such situations and thus optimize the management of ES. It
      was the aim oft this study to compare the precision achieved in documenting ES
      using an in-hospital emergency protocol (IHEP), specifically developed for
      documentation of ES, with that using a standard anesthesia protocol (SAP), to
      prove which format would reflect the facts of the ES in better detail. METHODS:
      All IHEP documented in hospital emergencies between 2005 and 2007 were
      retrospectively analysed in order to compare them with ES documented by SAP
      during the same period of time. RESULTS: 200 protocols (52 IHEP and 146 SAP were
      included. Due to a lack of adequate structuring the conventional anesthesia
      protocols reported most details of ES in plain text. In comparison IHEP
      documentation allowed a more detailed, precise and complete documentation of ES.
      CONCLUSION: IHEP, designed according to the well known DIVI out-of-hospital
      emergency protocol, seems to be superior to using an SAP. Using IHEP is
      practicable and results in well documented data of ES, both medical and legal
      aspects of documentation are regarded. Retrospective analysis to improve ES
      performance is quite feasible when using HIP.

PMID- 19847731
TI  - [Acute renal failure associated with malignant hypertension].
AB  - HISTORY AND CLINICAL FINDINGS: A 37-year-old woman was referred to the
      interdisciplinary emergency room with a high blood pressure and headaches. She
      complained about nausea and vomiting. She has been treated for hypertension for
      approximately 9 years in an outpatient clinic. INVESTIGATIONS: The patient's
      blood pressure was elevated up to 248/132 mm Hg. Emergency laboratory test
      revealed high blood creatinine (19,29 mg/dl) and blood urea nitrogen (365 mg/dl)
      along with the decreased haemoglobin concentration and normal thrombocytes.
      Urinalysis showed a mild hematuria and proteinuria. The CT-scan and sonography of
      the abdomen showed no relevant renal artery stenosis or any relevant intestinal
      organ damages. TREATMENT AND COURSE: An immediate antihypertensive medication was
      started in the emergency room, which resulted in a gradual decrease of blood
      pressure. Due to hypertension-induced acute renal failure, a hemodialytic
      treatment was initiated. After several sessions of hemodialysis, the levels of
      blood urea nitrogen and creatinine gradually decreased but remained elevated. The
      patient was included into the renal transplantation program due to the anuric
      renal failure. CONCLUSIONS: Acute renal failure associated with very high blood
      pressure and retinal bleedings is characteristics of malignant hypertension
      resulting frequently from pre-existing essential hypertension. In addition,
      uremia is a major cause of mortality in malignant hypertension. Excessive
      arterial pressure leads to endothelial damage of arterioles and capillaries. The
      ischemic collapse of glomerula promotes further irreversible renal injury, and
      eventually leads to a long-term hemodialysis or renal transplantation.

PMID- 19847732
TI  - [56-year-old patient with leg paresis, pulmonary infiltrates, and eosinophilia-
      Case 08/2009].
AB  - HISTORY AND ADMISSION FINDINGS: A 56-year-old woman presented with progressive
      dyspnea and polyneuropathia. Medical history revealed a bronchial asthma and
      hypertension. She was in a reduced general condition and had to be admitted to
      the intensive care unit for mechanical ventilation the same day. INVESTIGATIONS:
      The computed tomography of the chest revealed distinct pulmonary infiltrates.
      Laboratory findings showed significantly elevated inflammatory markers as well as
      an eosinophilia in the differential blood count and the bronchial lavage.
      Diagnostics for infections were all negative as were antinuclear and anti
      neutrophil cytoplasmatic antibodies (ANCAs). DIAGNOSIS, TREATMENT AND COURSE: An
      ANCA negative Churg Strauss Syndrome (CSS) was diagnosed in accordance with
      extravascular and blood eosinophilia, pulmonary infiltrates and the neurological
      symptoms. Aggressive therapy with high dose glucocorticosteroids and
      cyclophosphamide (CYC) pulses was initiated. The patient improved rapidly and was
      extubated 6 days after the initiation of treatment. After 6 cycles of CYC with
      750 mg/m2 and a maintenance treatment with azathioprine and 5mg prednisolone the
      patient is still in complete remission 2,5 years after the diagnosis. CONCLUSION:
      The CSS belongs to the ANCA-associated vasculitides. The patient described here
      presented with all the characteristic organ involvements of CSS and a fulminate
      worsening. The fast diagnosis and aggressive therapy which was started only hours
      after admission to the intensive care unit induced a long lasting remission.

PMID- 19847733
TI  - [68-year-old patient with syncope caused by climbing stairs].

PMID- 19847734
TI  - [Rare differential diagnosis of acute kidney injury--Case 09/2009].
AB  - HISTORY AND ADMISSION FINDINGS: A 44-year-old male and his 40-year-old wife, both
      previously in good health, were admitted for abdominal pain, diarrhea, vomiting,
      severe headache, and oliguria after ingestion of wild mushrooms two weeks
      earlier. Physical examination revealed costo-vertebral-angular tenderness in the
      husband and abdominal tenderness in both patients. INVESTIGATIONS: Laboratory
      showed acute renal injury with markedly increased serum concentrations of
      creatine and urea. On abdominal ultrasound, the kidneys were slightly increased
      in size with echogenic parenchyma and prominent medullary pyramids. Signs of an
      immunological or infectious etiology were missing. Histological investigation of
      the renal biopsy showed acute interstitial nephritis with marked tubular damage
      in both cases. DIAGNOSIS, TREATMENT AND COURSE: History and histological findings
      were consistent with Orellanus syndrome following ingestion of mushrooms of the
      Cortinarius species. In both patients, haemodialysis was initiated. In the
      husband, dialysis was discontinued on day 8 and a follow-up visit after one month
      revealed stage 5 chronic kidney disease. In the wife, continuation of
      haemodialysis in an ambulatory setting required implantation of a temporary
      vascular catheter. CONCLUSIONS: In cases of acute renal injury of unknown origin,
      ingestion of mushrooms of the Cortinarius species should be included in the
      differential diagnoses. In particular, initial gastrointestinal complaints may
      point to this rare differential diagnosis.

PMID- 19847735
TI  - [Elevated pancreatic enzymes without evident pancreatic disease].

PMID- 19847736
TI  - [Oncolytic virus therapy using vesicular stomatitis virus].

PMID- 19847737
TI  - [Management of tricuspid valve disease].

PMID- 19847738
TI  - [Information from foreign patients. Decision of the German Supreme Court from May
      8, 2008].

PMID- 19847739
TI  - [Dissociative identity disorder or schizophrenia?].
AB  - We present a case of dissociative identity disorder in which Schneiderian first
      rank symptoms were present besides of various states of consciousness. Thus the
      diagnosis of schizophrenia had to be considered. Formally, the symptoms met ICD
      10 criteria for schizophrenia. However, taking into account the lack of formal
      thought disorder and of negative symptoms as well as a typical history of severe
      and prolonged traumatisation, we did not diagnose a co-morbid schizophrenic
      disorder. There is good evidence for the existence of psychotic symptoms among
      patients with dissociative disorders. However, in clinical practice this
      differential diagnosis is rarely considered.

PMID- 19847740
TI  - Inter- and intraobserver reliability of predefined diagnostic levels in high
      resolution sonography of the carpal tunnel syndrome - a validation study on
      healthy volunteers.
AB  - PURPOSE: High-resolution ultrasound is becoming increasingly important in the
      diagnosis of carpal tunnel syndrome (CTS). Most studies define cut-off values of
      the cross-sectional area (CSA) of the median nerve in different locations. The
      individual range of nerve swelling, the size of the nerve, and its CSA are not
      addressed. The aim of the study is to define the intra- and interobserver
      reliability of diagnostic ultrasound using two different cross-sectional areas of
      the median nerve at the carpal tunnel in predefined locations. MATERIALS AND
      METHODS: Two observers using high-resolution ultrasound examined 50 wrists of
      healthy volunteers independently. The CSA of the median nerve was measured at the
      entrance of the carpal tunnel and 2 cm proximal to the palmar wrist crease. The
      height and width of the carpal tunnel were determined using anatomical landmarks.
      The intra- and interobserver reliability was determined using Cronbach's alpha.
      RESULTS: Depending on the observer, the mean width of the carpal tunnel ranged
      from 3.37 to 3.43 cm with the height ranging from 1.18 and 1.19 cm. The CSA of
      the nerve was measured with values of 8.43 and 9.05 mm (2) on the pisiform level
      and 9.37 and 9.68 mm (2) on the proximal level. Cronbach's alpha ranged from
      0.754 to 0.940 for the interobserver reliability and from 0.924 to 0.996 for the
      intraobserver reliability. CONCLUSION: To use high-resolution ultrasound for the
      diagnosis of carpal tunnel syndrome, the reproducibility of this method has to be
      evaluated. Our study confirms examiner-independent reproducibility of two
      predefined diagnostic cross-sectional areas resulting in good alpha values.

PMID- 19847741
TI  - True aneurysm of the antecubital vein.

PMID- 19847742
TI  - Ligustilide suppresses the biological properties of Danggui Buxue Tang: a Chinese
      herbal decoction composed of radix astragali and radix angelica sinensis.
AB  - Danggui Buxue Tang (DBT), a herbal decoction composed of Radix Astragali (RA) and
      Radix Angelica sinensis (RAS), has been used for treating menopausal irregularity
      in women for more than 800 years in China. According to the old tradition, RAS
      had to be processed with yellow wine before DBT preparation, which markedly
      reduced the amount of ligustilide in RAS and DBT, as well as enhanced the
      bioactivities of DBT. Here, we hypothesized that ligustilide would be an
      ingredient that possessed suppressive effects on DBT's functions. In the presence
      of ligustilide, the amount of astragaloside IV, calycosin, formononetin, and
      total polysaccharides extracted from RA were decreased. An increase of
      ligustilide caused a decrease of DBT's osteogenic activity in stimulating
      proliferation and differentiation of cultured bone cells. In addition, in the
      presence of a high level of ligustilide, DBT caused a side effect inducing the
      proliferation of breast MCF-7 cells. The current results strongly suggest that
      ligustilide is a negative regulator that hinders DBT to achieve its biological
      efficacy, which supports the traditional practice of preparing DBT using the
      ethanol-treated RAS.

PMID- 19847743
TI  - Chemical constituents from the rhizome of Acorus calamus L.
AB  - Three new sesquiterpenes, 1 beta,7 alpha(H)-cadinane-4 alpha,6 alpha,10 alpha
      triol (1), 1 alpha,5 beta-guaiane-10 alpha-O-ethyl-4 beta,6 beta-diol (2), and 6
      beta,7 beta(H)-cadinane-1 alpha,4 alpha, 10 alpha-triol ( 3), together with 25
      known ones, were isolated from the rhizome of Acorus calamus L. Their chemical
      structures were established on the basis of interpretation of spectroscopic data
      and comparison with those of the related known compounds.

PMID- 19847744
TI  - Development of a fast and convenient method for the isolation of triterpene
      saponins from Actaea racemosa by high-speed countercurrent chromatography coupled
      with evaporative light scattering detection.
AB  - In the present work, a fast and simple method for the separation and purification
      of triterpene saponins from Actaea racemosa was successfully established.
      Accelerated solvent extraction was used for defatting and extracting of the
      subaerial parts, giving a triterpene enriched crude extract. Size exclusion
      chromatography was used to separate actein and 23-epi-26-deoxyactein from other
      triterpenoids, which were collected in a third fraction. This most complex third
      fraction was applied to high-speed countercurrent chromatography, a well
      established technique for the separation of saponins. Separation parameters were
      first optimized on an analytical level, using a hyphenated HSCCC-ELSD setup,
      before the system was scaled up to preparative size. The resulting two-phase
      solvent system, consisting of N-hexane-acetone-ethyl acetate-2-propanol-ethanol
      water (3.5 : 1 : 2 : 1 : 0.5 : 2, v/v/v/v/v/v), enabled the isolation of 23-O
      acetylshengmanol-3-O- beta-D-xylopyranoside (17.4 mg), cimiracemoside D (19.5
      mg), 25-O-acetylcimigenol-3-O-beta-D-xylopyranoside (7.1 mg) and the aglycone
      cimigenol (5.9 mg). Purity of the isolated substances was 96.8 %, 96.2 %, 97.9 %,
      and 98.4 %, respectively. The same method was suitable for the purification of
      actein and 23-epi-26-deoxyactein, with purities of 97.0 % and 98.3 %.

PMID- 19847745
TI  - Antibacterial compounds from mushrooms II: lanostane triterpenoids and an
      ergostane steroid with activity against Bacillus cereus isolated from Fomitopsis
      pinicola.
AB  - Anti- Bacillus cereus bioassay-guided fractionation of a crude extract of the
      American mushroom, Fomitopsis pinicola, was performed using thin-layer
      chromatography, Sephadex LH-20 column chromatography, and preparative-scale HPLC.
      Five lanostane triterpenoids (1-5) and one ergostane steroid (6) were isolated
      and identified. Compound 1 is a new lanostane triterpenoid, and its structure was
      determined using 1D and 2D NMR experiments, HR-MS, and physical data. Each of the
      purified compounds (1-6) was tested for antibacterial activity against B. cereus
      using standard MIC assays. Compounds 1-6 had MIC values of 32, 16, 32, 32, 128,
      and 64 microg/mL, respectively.

PMID- 19847746
TI  - Decompressive hemicraniectomy for space-occupying cerebral infarction.
AB  - The development of a space-occupying hemispheric infarction occurs in a subset of
      patients with ischaemic cerebrovascular stroke. It is a life-threatening
      condition with a high mortality rate of up to 80% with medical therapy alone.
      Previous retrospective and uncontrolled case series have suggested that
      decompressive hemicraniectomy can significantly reduce mortality to 20-30%
      compared to conservative treatment. This evidence has now been confirmed by the
      data of prospective randomised studies. The data also indicate that the reduction
      of mortality is not accompanied by an increase in the number of completely
      disabled patients. However, the number of disabled patients depending on the
      assistance of others increases significantly, and the patients and their
      caregivers need to be comprehensively informed about the long-term consequences
      prior to surgery. Furthermore, questions concerning the optimal time point for
      decompression and the upper age limit at which patients still benefit from
      surgery remain unanswered. Thus the indication for surgery is to a great extent
      still dependent on the individual situation of the patient and the experience of
      the treating physicians. This review covers the indications, the surgical
      technique, the prognostic factors and the clinical outcome with this procedure
      based on the data of retrospective series and the results of the recently
      published prospective randomised trials.

PMID- 19847747
TI  - Reanimation of the paralyzed face.

PMID- 19847749
TI  - Utilizing dynamic rods with dynamic screws in the surgical treatment of chronic
      instability: a prospective clinical study.
AB  - AIM: In this study, we examined the results of utilizing the agile posterior
      dynamic stabilization system with dynamic transpedicular screws in our patients.
      MATERIAL AND METHODS: Posterior dynamic instrumentation with agile rods and
      dynamic transpedicular screws was employed in 15 (seven male and eight female)
      patients (mean age = 42, ranging from 30 to 53). The average follow-up duration
      was 19 months (ranging from 12 to 25). The primary purpose for the surgery was
      degenerative disc disease. For subjective evaluation, patients underwent a
      physical examination utilizing the Oswestry disability index (ODI) and visual
      analogue scale (VAS). Radiographic parameters, including the angle of lumbar
      lordosis (LL), angle of segmental lordosis (alpha) and intervertebral space
      (IVS), were also evaluated. Both subjective patient evaluations and radiographic
      parameters were assessed at the 3rd and 12th postoperative months. RESULTS:
      Significant postoperative improvements were observed in the ODI and VAS
      measurements (P < 0.05). There were no significant differences in the LL, alpha
      and IVS parameters. One patient experienced a broken screw. CONCLUSION: We
      obtained good clinical results by utilizing dynamic rods with dynamic
      transpedicular screws.

PMID- 19847748
TI  - [Purple glove syndrome - a case report].
AB  - The purple glove syndrome (PGS) is a soft tissue injury after peripheral
      intravenous phenytoin administration or oral overdosage. The incidence of PGS is
      described with 0-6%. Typical symptoms are purple discoloration, oedema, pain, and
      a decrease of range of motion. In severe cases PGS may lead to abscess, skin loss
      and compartment syndrome. The established treatment of PGS is immediate
      interruption of phenytoin injections, splinting, elevation, and close
      observation. In cases of severe complications (e. g., compartment syndrome),
      surgical intervention is necessary. The case of a 40-year-old female patient is
      reported who was transferred to our department 4 days after intravenous phenytoin
      administration and who underwent successful surgical revision.

PMID- 19847750
TI  - Risk factors for low back pain and its relation with pain related disability and
      depression in a Turkish sample.
AB  - AIM: To investigate the relation of depression and pain-related disability
      associated with Low Back Pain (LBP). MATERIAL AND METHODS: The Quebec Back Pain
      Disability Scale, Visual Analogue Scale (VAS) and Zung Depression Scale were sent
      to 3800 randomly select adults in Kayseri, Turkey. The demographic
      characteristics of the participants (Socioeconomic status, age etc) and low back
      pain (frequency, intensity, duration) features together with pain-related factors
      were investigated in responding participants. The participants who had self
      reported LBP during the study period were accepted as the study group. RESULTS:
      807 (37.1%) of the participants reported that they had low back pain at the time
      of interview. The study group had a score of 52.91+/-24.20 mm for VAS, 52.30+/
      10.67 for the Zung Depression Scale and 24.53+/-17.22 for the Quebec Back Pain
      Disability Scale. Age, female gender, smoking ( > 20 cigarettes per day), low
      socioeconomical status and living in a rural habitat were found to be associated
      with low back pain. Depression (P= 0.017) and disability (P= 0.002) were found to
      be independent risk factors for VAS. CONCLUSION: Determination of the frequency
      and intensity of low back pain and related factors is needed for the prevention
      and management of pain. Mood disorders and self reported restriction in daily
      activities should be screened in patients with low back pain.

PMID- 19847751
TI  - Acute subdural hematomas caused by ruptured aneurysms: experience from a single
      Turkish center.
AB  - AIM: Although an aneurysmal rupture typically presents on computed tomography
      (CT) imaging as only a subarachnoid hemorrhage (SAH), it may be associated with
      spontaneous (nontraumatic) subdural hemorrhage (sSDH). The purpose of this paper
      is to discuss the clinical and radiological characteristics, as well as a
      potentially dangerous situation in the diagnosis and the management of this life
      threatening condition. MATERIAL AND METHODS: The Department of Neurosurgery at
      Inonu University (Turgut Ozal Medical Center) (TOMC) maintains a prospective
      database of all patients treated for intracranial aneurysms since 1999. Using
      this database, we obtained patients with ruptured aneurysms who presented with
      sSDH on CT imaging. RESULTS: 687 patients with radiographically documented
      ruptured aneurysms were admitted from January 2000 through January 2009. Of
      these, eleven patients presented with sSDH. The incidence of aneurysmal rupture
      with sSDH is 1.6 % in our series. CONCLUSION: Acute sSDH on cranial CT should be
      considered for an urgent workup of a ruptured aneurysm, even in the absence or
      presence of SAH finding. CT angiography has advantages over cerebral digital
      substraction angiography (DSA) and may be a reasonable alternative to latter
      modality in the diagnosis, triage, and treatment planning in patients with sSDH.

PMID- 19847752
TI  - Spontaneous primary intraventricular hemorrhage in adults: clinical data,
      etiology and outcome.
AB  - AIM: Primary intraventricular hemorrhage (PIVH), bleeding in the ventricular
      system without a recognizable parenchymal component, is a rare neurological
      disorder. The purpose of this study was to identify clinical features, risk
      factors, etiology and outcome of patients with PIVH. MATERIAL AND METHODS: We
      retrospectively reviewed the clinical data, complementary examinations, outcome
      and computed tomography (CT) IVH score of 24 patients in our hospital from 2004
      to 2008. We identified 24 patients with the inclusion criteria of non-traumatic
      PIVH. Their mean age was 60.6+/-17.4 years (range 38-79). Fourteen patients were
      male and 10 were female. RESULTS: The major symptoms included headache (n=24),
      loss of consciousness (n=6), confusion and disorientation (n=14), nausea/vomiting
      (n=10). Angiography revealed vascular malformations in five patients (21%). Other
      possible causative factors were hypertension in 12 patients (50%) and clotting
      disorder in one. The aetiology remained unknown in six patients. Most PIVH
      patients had associated hydrocephalus (58%) and 37% of the patients required
      ventricular drainage. In-hospital mortality was high (41%) and a FOUR score
      <or=10, GCS <or=8 and early hydrocephalus were independent predictors of
      mortality. CONCLUSION: Hypertension is the most common associated risk factor for
      PIVH followed by vascular malformation. Spontaneous resorption and rebleeding may
      be seen. The neurological status of the patients and an early developing
      hydrocephalus are the most important risk factors.

PMID- 19847753
TI  - Bilateral C1-C2 claw for atlantoaxial instability.
AB  - OBJECTIVE: Atlantoaxial stability can be achieved by laminar hook systems via
      posterior approach. This technique is much more safer than using screws. We
      presented our experience with the C1-C2 claw procedure. METHODS AND MATERIAL:
      Seven patients with atlantoaxial instability were operated by using C1 and C2
      hooks, rods and transverse connector at Neurosurgery Clinic of Istanbul
      University Cerrahpasa Medical Faculty between the years 2005 and 2008. RESULTS:
      Satisfactory stabilization was achieved in all patients. Operative complication
      or instrumentation failure was not observed. CONCLUSIONS: C1-C2 claw is a safe
      technique and adequate stabilization is achieved with the use of a transverse
      connector.

PMID- 19847754
TI  - The variations of the anterior choroidal artery: an intraoperative study.
AB  - AIM: Increasing use of surgical magnification for operations in the territory of
      the anterior choroidal artery (AChA) has created a need for detailed knowledge of
      their anatomical variations. The aim of the present study is to examine the
      anatomical variations of the AChAin patients operated via pterional approach.
      MATERIAL AND METHODS: The origin and branching pattern of AChAs were observed
      intraoperatively in 130 patients who were operated via a pterional approach at
      our center. RESULTS: AChAs arose from the internal carotid artery (ICA) and
      distal to the posterior communicating artery (PCoA) at a ratio of 70%, from just
      distal to the original point of the PCoA in 20%, and from just proximal to the
      ICA bifurcation in 10% of the patients. In 95 cases, AChAs arose from the
      inferolateral aspect of the ICA in the posterolateral aspect in 27 and from its
      lateral part in 8 cases. AChAs were found as a single branch at the origins from
      ICA in 110 patients, as double in 17 cases and as triple in 3 patients.
      CONCLUSION: Recognition of anatomical variations and microvascular relationships
      of AChA will allow neurosurgeons to construct a better and safer microdissection
      plan, to save time and can prevent postoperative neurological deficits.

PMID- 19847755
TI  - Analysis of serum pro-inflammatory cytokine levels after rat spinal cord
      ischemia/reperfusion injury and correlation with tissue damage.
AB  - AIM: A rat model of spinal cord ischemia/reperfusion was conducted and the serum
      cytokine levels and histopathological changes were assessed. MATERIAL AND
      METHODS: Twenty-four male Sprague-Dawley rats were assigned into four
      experimental groups. Group-A (the sham operated rats) and group-B (the spinal
      ischemia/reperfusion group) were sacrificed at 24 hours postoperatively while
      group-C (the sham operated rats) and group-D (the spinal ischemia/reperfusion
      group) were sacrificed at 48 hours. Histopathological changes in the spinal cords
      and serum cytokine levels were analysed. RESULTS: All three proinflammatory
      cytokine levels reached significantly higher levels compared to the sham operated
      groups in both the 24-hour and 48-hour spinal cord ischemia/reperfusion groups.
      CONCLUSION: Inflammation is a plausible pathway in spinal cord
      ishemia/reperfusion injury. However clinical treatment of the damage does not
      currently include antiinflammatory therapy. The results of our study supported
      the hypothesis that inflammatory responses could play a possible role in the
      ischemia/reperfusion injury of the spinal cord. Characterization of the role of
      inflammation in the etiopathogenesis of ischemia/reperfusion injury to the spinal
      cord is important to facilitate the development of novel therapeutic approaches
      for prevention and/or treatment of this severe condition.

PMID- 19847756
TI  - The effect of nitrogen mustard on the rat brain and the therapeutic value of
      proanthocyanidin.
AB  - AIM: Nitrogen Mustard (NM) is an alkylating agent that damages cellular nuclear
      DNA after penetrating tissue. This results in cytostatic, mutagenic and cytotoxic
      effects. We used the electron microscope to investigate the effect of NM gas
      administered through the dermal and respiratory routes to rats on the brain
      cortex and also tried to show whether the antioxidant Proanthocyanidin (PC) could
      decrease this effect. MATERIAL AND METHODS: A total of 32 rats were randomized
      into four groups: Group I: Control group, Group II: PC group, Group III: NM
      group, Group IV: NM + PC group. The rats were sacrificed 3 days after NM gas
      exposure. A segment of the cortical tissue was prepared for electron microscopy.
      RESULTS: We used the electron microscope for cellular analysis of NM on cortical
      neural cells. These investigations revealed degeneration of the cortical neural
      cell nuclei together with oedema and axonal degeneration in the subcortical
      neural tissue. The group receiving antioxidants was found to have less oedema and
      degeneration. CONCLUSION: These findings imply that structural changes induced by
      mustard gas can be prevented and restored by proanthocyanidin treatment.

PMID- 19847757
TI  - The preventive effect of mexiletine on cerebral ischemic injury following
      experimental middle cerebral artery occlusion.
AB  - AIM: Previous studies demonstrated that mexiletine has some important features in
      the prevention of ischemic brain injury such as sodium and calcium canal blockage
      and free radical occurrence. Our aim was to investigate the effects of mexiletine
      on ischemic brain injury. MATERIAL AND METHODS: Experiments were performed on 30
      adult male Sprague- Dawley rats (285-425 g). Left middle cerebral artery
      occlusion following microcraniectomy and simultaneous bilateral carotid artery
      occlusion were performed. Three different treatments were included in this study:
      (a) "naive" control group (no drug applied; n = 10); (b) "sham surgery" control
      group (only saline was applied; n = 10); and a (c) "treatment group (n = 10)
      where mexiletine was applied. After 24 h from ischemic insult, all rats were
      decapitated and prepared for immunocytochemical and histopathological analyses.
      Cerebral infarct volumes were calculated and compared using ANOVA and a Post- Hoc
      Bonferroni test in each group statistically. RESULTS: The results showed
      statistically significant differences between the treatment (81.98 +/- 12.58
      mm?), control (121.57 +/- 11.41 mm?) and sham (116.08 +/- 12.36 mm?) groups (p <
      0,0001), respectively. CONCLUSION: Mexiletine should be considered as an
      alternative medication for prevention and treatment of ischemic brain injury due
      to its multipotent effects.

PMID- 19847758
TI  - The effects of intravenous cilostazol and nimodipine on cerebral vasospasm after
      subarachnoid hemorrhage in an experimental rabbit model.
AB  - AIM: Our aim in this study was to investigate the efficacy of intravenous
      administration of cilostazol and compare these effects with intravenous usage of
      nimodipine in subarachnoid hemorrhage model. MATERIAL AND METHODS: Twenty-five
      male New Zealand White rabbits were assigned randomly to 1 of 5 groups. Animals
      in group 1 (n=5) served as controls, group 2 (n=5) was the SAH-only group, group
      3 (n=5) was treated with intravenous 10 mg/kg cilostazol, group 4 (n=5) was
      treated with 0.05 mg/kg intravenous nimodipine, and group 5 (n=5) served as the
      vehicle group and treated with a mixture of dimethyl sulfoxide and phosphate
      buffer solution. Basilar arteries were removed from the brain stems and analyzed.
      The vessels were measured using computer-assisted morphometry (SPOT for Windows
      Version 4.1). Statistical comparisons were performed using the Kruskall-Wallis
      and Mann-Whitney U tests. RESULTS: Basilar artery wall thicknesses in group 3 and
      4 were smaller than the group 2 and this was statistically significant at p <
      0.05. The mean arterial cross-sectional areas in group 3 and 4 were higher than
      group 2 and this was also statistically significant at p < 0.05. CONCLUSION: Our
      results demonstrate that intravenous administration of both cilostazol and
      nimodipine significantly attenuates cerebral vasospasm after SAH.

PMID- 19847759
TI  - Effect of a chloride channel inhibitor, 5-nitro-2- (3-phenylpropylamino)
      benzoate, on endothelin-1 induced vasoconstriction in rabbit basilar artery.
AB  - AIM: Endothelin-1 (ET-1) has been implicated in the pathophysiology of cerebral
      vasospasm. Chloride (Cl-) channels exist in vascular smooth muscle and activation
      of these channels leads to depolarization and contraction. The aim of the present
      study was to test the effect of 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB),
      a Cl- channel antagonist, on the ET-1-induced cerebral vasospasm in rabbit
      basilar artery and thus investigate the contribution of Cl- channels. MATERIAL
      AND METHODS: Thirty rabbits were divided into five groups and received intra
      arterial injection of isotonic saline (Group I, n=6), ET-1 (group II, n=6), ET-1
      plus NPPB (Group III, n=6), dimethylsulfate (DMSO4) (Group IV, n = 6) and NPPB
      (Group V, n=6). Pre and post injection basilar artery diameters were measured in
      each group and transmission electron microscopic investigations on basilar
      arteries were performed. RESULTS: The mean pre-injection and post-injection
      vessel diameters were 0.8833 mm and 0.7000 mm in ET-1 group, 0.6833 mm and 0.8500
      mm in ET-1 + NPPB group. NPPB administered prior to ET-1 injection, prevented the
      ET-1-induced vasoconstriction. Additionally, NPPB prevents the ET-1 induced
      changes in vessel wall and neurons in the brain stem. CONCLUSION: The results of
      this study add further insights to our armamentarium against cerebral vasospasm.

PMID- 19847760
TI  - Effect of cepea extract-heparin and allantoin mixture on epidural fibrosis in a
      rat hemilaminectomy model.
AB  - AIM: Epidural fibrosis following a laminectomy procedure is a serious problem
      that results in failed back surgery syndrome. Aserious number of manuscripts have
      explained its possible mechanism and results but no effective preventive surgical
      technique or treatment is currently present. MATERIAL AND METHODS: We used a rat
      hemilaminectomy model at lumbar fourth level. In the treatment group (n:10), the
      hemilaminectomy sites were filled with cepea extract-allantoin and heparin
      mixture as sterile cream form. In the second group, the same surgical procedure
      was performed and the site was filled with physiological saline. All animals were
      terminated after 6 weeks and laminectomy sites removed en-bloc. Epidural fibrosis
      was evaluated and compared using semi-quantitative histopathological scoring
      scales. RESULTS: In the physiological saline group, the fibrosis score was 10.3
      points and 90% of the subjects had acute inflammatory reaction, 80% chronic
      inflammatory reaction and 100% showed bone destruction and reparation process. In
      the cepea extract group, these values were fibrosis score 4.2 points, 0% acute
      inflammatory reaction, 33.3% chronic inflammatory reaction and 10% bone
      destruction and reparation process, respectively. CONCLUSION: This study showed
      that aloe cepea extract-allantoin and heparin mixture diminished epidural
      scarring formation effectively with decreased scores of acute and chronic
      inflammation, compared to the physiological saline solution group.

PMID- 19847761
TI  - Effect of smoking on rat basilar artery: correlation with inducible nitric oxide
      synthase and endothelin converting enzyme-1.
AB  - AIM: Smoking is an extremely important risk factor for subarachnoid hemorrhage
      and seems to increase rupture risk of unruptured aneurysms by accelerating their
      growth rate. The aim of the study was to investigate the effect of smoking on the
      luminal diameter with wall thicknesses of rat basilar arteries and to detect
      alterations of inducible nitric oxide synthase and endothelin-converting enzyme 
      1 in the endothelial cells. MATERIAL AND METHODS: Rats were divided into two
      groups. The level of middle pons slices were embedded in paraffin before they
      were stained with hematoxylin and eosin. Rabbit anti-human inducible nitric oxide
      synthase and endothelin converting enzyme-1 antibodies were used. RESULTS:
      Significant decrease of the vessel luminal diameter and increase of the vessel
      wall thickness were found in chronic smokers in our study. There was a linear and
      significant (p= 0,023, r =0,704) correlation between thickness of the wall and
      endothelin converting enzyme-1 immune reaction. Correlation was not found with
      inducible nitric oxide synthase (p > 0.05). CONCLUSION: This study on the
      comparison of vessel luminal diameter and vessel wall thickness with inducible
      nitric oxide synthase and endothelin converting enzyme-1 immune reactions
      revealed that the main effect of smoking on the vessel wall is associated with
      endothelin converting enzyme-1.

PMID- 19847762
TI  - Spinal dysraphisms of the cervicothoracic region in childhood.
AB  - PURPOSE: Spinal dysraphisms are the most common congenital anomalies of the CNS.
      Spinal dysraphism (SD) of cervical and upper thoracic region are rare,
      demonstrating distinct clinical and structural configurations compared to lumbar
      counterparts. METHODS: In Haydarpasa Numune Hospital, a total of 7 cases (3 male
      and 4 female) ranging between 20 days to 9 years of age with cervicothoracic SD
      were operated on between 2002 and 2008. The sacs were located in the cervical and
      thoracic region in 4 and 3 of the cases, respectively. The associated anomalies
      were diagnosed in 3 cases, including SCM type 2, Chiari type 2, hyrocephalus and
      hydromyelia. All cases underwent surgical treatment that involves excision of the
      sac and intradural exploration providing untethering of the spinal cord.
      Postoperative follow up of these patients was uneventful and neither neurological
      deficits nor complications were observed. CONCLUSION: Cervicothoracic SD has more
      favorable outcome in respect to neurological, orthopaedic and urologic problems
      compared to lumbar counterparts. In order to prevent forthcoming neurological
      deterioration, surgical treatment consisting of intradural exploration of the
      lesion, untethering of the spinal cord and excision of potential adhesions should
      be performed in the early period.

PMID- 19847763
TI  - Neuroproctective effects of ischemic tolerance (preconditioning) and
      postconditioning.
AB  - Elucidation of the endogenous cell survival pathways involved in ischemic
      tolerance (preconditioning) and postconditioning has significant clinical
      implications for preventing neuronal damage in susceptible patients. Ischemic
      tolerance is a phenomenon in which the brain protects itself against future
      injury by adapting to low doses of noxious insults. Ischemic postconditioning is
      defined as brief periods of reperfusion alternating with re-occlusion applied
      during the very early minutes of reperfusion that mechanically alters the
      hydrodynamics of reperfusion. Similar pathways and molecules play a role in pre
      and postconditioning but their roles and timing are different in each
      conditioning. Understanding the neuroprotective effects of mechanisms underlying
      conditioning has been elusive, but NMDA receptor activation, nitric oxide,
      inflammatory cytokines, and suppression of the innate immune system appear to
      have a role. Reactive oxygen species and classical ligand stimuli play a role in
      postconditioning with KATP channels and protein kinase C pathways acting as
      mediators.

PMID- 19847764
TI  - Vertebral artery insult at the transverse foramina by gun shot wounds: report of
      two cases.
AB  - The vertebral artery (VA) is well protected through its course at the cervical
      transverse foramina and penetrating injuries of VA are mostly caused by gun shot
      wounds. The mechanism of injury in these wounds is described as the kinetic
      energy transferred by the bullet, which always depends on its mass and speed.
      Thus, the size of the pellet is the most important factor for the tissue damage,
      shock waves and direct injury. Civilian gun shot wounds are generally caused by
      low velocity firearms, In this report, we described two cases with cervical
      gunshot wound characterized with transverse foramina damage and VA insult. The
      first patient was assaulted by bullet that resulted in vertebral artery
      occlusion, whereas a smaller pellet was found in the second one and arterial flow
      was not influenced on the site of the damaged transverse foramina. Successful
      management of these injuries should include careful analysis of the bullet
      characteristics that is directly related to the intensity of damage.

PMID- 19847765
TI  - Gliosarcoma with chondroblastic osteosarcomatous differentation: report of two
      case with clinicopathologic and immunohistochemical features.
AB  - Gliosarcoma is a rare tumor of the central nervous system characterized by a
      biphasic histological pattern. Our objective is to describe clinical,
      morphological and immunohistochemical features of two cases of gliosarcoma with
      chondroblastic osteosarcomatous differentiation and to discuss its pathogenetic
      mechanisms. CASE 1: A 52- year-old male patient underwent parietal craniotomy due
      to anaplastic ependymoma. The case had radiotherapy and chemotherapy
      postoperatively. After the first operation, additional resections were performed
      for tumor because of recurrences at the fourth, seventh and tenth months. The
      patient died after the last tumor resection. Histopathologic examination of the
      postmortem biopsy revealed neoplasm displaying a biphasic morphologic pattern
      including both gliomatous and sarcomatous components. CASE 2: The case was a 69
      year-old male patient with a right frontal lobe mass histologically diagnosed as
      gliosarcoma displaying sarcomatous and glial components. Immunohistochemical
      features were similar to those of the first case in general, but diffuse nuclear
      reaction with p53 protein was detected in both components. We report two cases
      with an extremely rare histopathological diagnosis of "gliosarcoma with features
      of chondroblastic osteosarcoma".

PMID- 19847766
TI  - Giant cell reparative granuloma of the axis.
AB  - Giant cell reparative granuloma (GCRG) is a rare, benign fibroosseous lesion. It
      typically arises in the mandible and maxilla, and less frequently in the skull
      bones. We report a case of GCRG of the axis, which is the first to be reported in
      the literature. A 35-year-old man was admitted to our clinic with the complaint
      of pain at his neck. There was no neurological deficit. CT and MRI showed a
      lesion destructing the body of the axis. Biopsy specimens were taken through the
      transoral-transpharyngeal route. Histopathological diagnosis was GCRG. The lesion
      was removed subtotally by the same route. We filled the tumor cavity with a bone
      graft and the patient was discharged with a halo brace without any neurological
      deficits. The follow-up CT revealed one year after the surgery showed sclerosis
      at the tumor site. The etiopathogenesis of GCRG is still controversial and the
      differential diagnosis, especially from giant cell tumor of bone is quite
      difficult. The treatment of choice for these lesions is complete surgical
      removal. Some authors recommend radiotherapy if total removal fails.

PMID- 19847767
TI  - Combined anterior and posterior approach for sacral/retroperitoneal hydatid cyst
      disease: case report.
AB  - Achieving complete resolution of spinal hydatid cyst disease is quite challenging
      when bone is involved. Many authors reported the poor outcome of posterior
      decompression and laminectomy for intraosseous spinal hydatid disease. In an
      attempt to avoid a similar poor outcome, hydatid cysts were reached via both
      anterior and posterior surgical approaches in our patient. A 73-year-old man
      presented with complaints of low back and right leg pain. Symptoms or signs of
      systemic hydatid cyst disease were absent. MRI demonstrated a cystic lesion in
      the presacral/retroperitoneal region, involving the body of the sacrum and sacral
      canal. Computed tomography images showed enlargement of the sacral foraminae. The
      multiseptated cysts and their contents were isodense with cerebrospinal fluid.
      The cysts were removed via an anterior extraperitoneal approach, using a
      paramedian vertical incision, and then were also approached posteriorly via
      bilateral S1 hemilaminectomy. No neurological deficits occurred following
      surgery. The patient's symptoms completely disappeared after this combination of
      aggressive surgery and antihelminthic therapy. The application of both anterior
      and posterior approaches to intraosseous sacral hydatid cysts may be preferred
      when faced with hydatid disease in this location.

PMID- 19847768
TI  - Glioblastoma multiforme mimicking arteriovenous malformation.
AB  - Glioblastoma multiforme is the most common intracranial neoplasm of all primary
      central nervous system tumors. Glial tumors can present in different forms.
      Intracranial hemorrhage may occur in all central nervous system tumors to a
      varying degree and extent and may even be massive. A 58-year-old man presented
      with intraparenchymal hemorrhage manifesting as severe headache and vomiting.
      Cranial computed tomographic scans revealed a right posterior temporoparietal
      intraparenchymal hemorrhage. Cerebral angiography revealed a 3 x 2 cm right
      inferior parietal arteriovenous malformation. The patient underwent surgical
      treatment with a diagnosis of arteriovenous malformation. Postoperatively, the
      histological diagnosis was glioblastoma. Glioblastoma may mimic an arteriovenous
      malformation. Close follow-up of such patients is essential.

PMID- 19847769
TI  - Cervical screw missing secondary to delayed esophageal fistula: case report.
AB  - Although anterior surgical approaches to the cervical spine have become popular
      and safe in recent years, they also have some complications. We present a case of
      loss of an anterior cervical plate screw by the natural tracts. The patient was a
      47- year-old woman who was operated on for cervical spondylotic myelopathy at
      another institution. Surgical interference included two levels of anterior
      discectomy, iliac graft placement and fixation using plate and screws. Two years
      later, plate dislocation and partial migration of the upper screws were observed.
      After 7 years the patient complained of dysphagia and she accepted removal of the
      osteosynthesis. Radiographical examination showed that one of the upper screws
      was missing and two lower screws were broken. Esophageal perforation was found
      during the surgery and repaired. Further progress was favourable. Complications
      associated with esophageal perforation may range from massive infection and death
      to spontaneous recovery. Erosion of the esophageal wall due to extruded bulky
      constructs may lead to a persistent fistula, abscess or septic diffusion.
      Spontaneous perforation of the esophagus and screw loss via the gastrointestinal
      tract make this case interesting..

PMID- 19847770
TI  - Coarctation of the aorta in adults: preoperative evaluation with multidetector CT
      angiography.
AB  - PURPOSE: To evaluate the reliability of 16-slice multidetector computed
      tomographic (MDCT) angiography for the preoperative morphologic assessment of
      coarctation of the aorta in adults. MATERIALS AND METHODS: Twenty-four adult
      patients with clinical suspicion of coarctation of the aorta who underwent both
      Doppler echocardiography and MDCT angiography were included in this study. The
      sensitivities of diagnosis were assessed comparing MDCT and Doppler
      echocardiography with surgical results. RESULTS: The overall sensitivity of three
      dimensional MDCT for diagnosis of the coarctation of the aorta was 100%, which
      was higher than that of Doppler echocardiography (91%). The overall sensitivity
      of MDCT for the assessment of cardiac defects was 82%, which was lower than that
      of Doppler echocardiography (100%). CONCLUSION: MDCT angiography with multiplanar
      and three-dimensional techniques should be the method of choice for preoperative
      morphologic assessment of coarctation of the aorta in adult patients.

PMID- 19847771
TI  - Congenital cystic eye with multiple dermal appendages and intracranial congenital
      anomalies.
AB  - Congenital cystic eye (anophthalmia with cyst) is an extremely rare anomaly
      discovered at birth with few reported cases in the literature, resulting from
      partial or complete failure during invagination of the primary optic vesicle
      during fetal development. Herein we present the radiographic, ultrasound, and
      magnetic resonance imaging findings of a unique case of congenital cystic eye
      associated with dermal appendages and advanced intracranial congenital anomalies
      in a 3-month-old boy.

PMID- 19847772
TI  - MRI of recurrent isolated cerebral Whipple's disease.
AB  - Whipple's disease is a rare systemic bacterial infection, characterized
      predominantly by gastrointestinal symptoms. Neurological symptoms are frequent in
      the course of the disease; however, a purely neurological presentation is
      uncommon. Diagnosis is confirmed with biopsy and polymerase chain reaction
      studies. Magnetic resonance imaging (MRI) findings vary, most commonly showing
      increased signal intensity on T2-weighted images. Contrast-enhanced images and
      diffusion- weighted imaging are useful to demonstrate meningeal enhancement and
      any accompanying infarcts. Brain biopsy is often performed, and MRI is crucial to
      guide the biopsy. Cerebral Whipple's disease is a long-lasting infection
      requiring long-term follow-up of these patients. MRI should be performed to
      detect any potential recurrence. We present a case of recurrent isolated cerebral
      Whipple's disease in a 68-year-old man with atypical presentation and MRI
      findings.

PMID- 19847773
TI  - MRI of omphalopagus conjoined twins with a Dandy-Walker malformation: prenatal
      true FISP and HASTE sequences.
AB  - Conjoined twins are an extremely rare congenital malformation without any known
      genetic predisposition. Omphalopagus twins are the second most common variety of
      conjoined twins and usually are joined at the umbilicus. We present omphalopagus
      conjoined twins demonstrated with true FISP (fast imaging with steady-state
      procession) and HASTE (half- Fourier acquisition single-shot turbo spin-echo)
      magnetic resonance imaging (MRI) sequences, which showed Dandy- Walker
      malformation in one of the pair. To our knowledge, this is the first case of
      conjoined twins with this malformation, which was diagnosed with ultrafast MRI.

PMID- 19847774
TI  - Post-partum testosterone administration does not reverse the effects of perinatal
      exposure to cadmium on rat offspring development.
AB  - This study investigated the effects of perinatal cadmium exposure on physical and
      reflexologic development of pup rats. It was examined if the immediate postpartum
      testosterone administration was able to reverse the toxic effects of the metal.
      Forty Wistar pregnant rats were divided into three groups: control and 10 and 20
      mg kg(-1) per day of cadmium chloride. These dams were treated from gestational
      days 18 to 21, and until the 7th lactation day. Immediately after birth, half of
      the offspring from the experimental and control groups received 50 microL of
      testosterone 0.2% i.p. The maternal body weight gain, food and water consumption
      were measured during the treatment period. In pups, the body weight, body length,
      physical landmarks, reflex development and the general activity were assessed.
      Results showed that: only 20 mg kg(-1) cadmium induced maternal toxicity; pup
      body weight and body weight gain were reduced in all experimental groups; only
      the cadmium-exposed offspring not treated with testosterone treatment showed a
      reduction in body length and body length gain; cadmium highest dose reduced the
      anogenital index in pups and delayed physical and reflexes development; and
      cadmium effects on the offspring, except in body length gain, were not reversed
      by testosterone. The results indicate that perinatal maternal exposure to cadmium
      promoted changes in the development of male rat offspring, reprogramming the
      pup's development. Testosterone administration was not able to reverse the
      cadmium effects, even on those parameters more directly related to the androgenic
      system as the testis descent and anogenital distance delays.

PMID- 19847776
TI  - Backbone dynamics of TFE-induced native-like fold of region 4 of Escherichia coli
      RNA polymerase sigma70 subunit.
AB  - Folding of a recombinant protein rECsigma(70) (4) comprising domain 4 of E. coli
      RNA polymerase sigma(70) subunit, upon addition of 2,2,2-trifluoroethanol (TFE)
      to its aqueous solution, was monitored by heteronuclear NMR spectroscopy. The TFE
      induced migration of resonance signals in a series of (15)N-HSQC spectra
      displayed sequence-dependent heterogeneity. A common trend of uniform upfield
      shift in both (1)H and (15)N dimensions, indicative of generation of helical
      structures, breaks down for some residues almost cooperatively at 10-15% TFE
      (v/v), pointing to the buildup of non-helical regions separating the initially
      induced helices. The preferences of residues to assume either helical or non
      helical conformation are correlated with the location in the sequence rather than
      with their type. CSI descriptors and (15)N relaxation data obtained for the
      protein at 10% TFE allowed characterization of the stability of the pre-folded
      state of rECsigma(70) (4). By all the criteria applied, three highly populated
      alpha-helical regions separated by much more flexible residues forming a loop and
      a turn in the DNA-binding HLHTH motif were identified. The location of the
      secondary structure elements along the protein sequence coincides with those
      found in homologous proteins, and with the helix nucleation regions determined in
      unfolded rECsigma(70) (4) at low pH. The bimodal distribution of the (15)N
      relaxation parameters enabled identification of residues forming a framework of
      the folded protein strictly corresponding to the HLHTH motif, bracketed by
      unfolded terminal regions. Thus, in respect to rECsigma(70) (4) in aqueous
      solution TFE acts not only as a strong helix inducer, but also as a folding
      agent.

PMID- 19847775
TI  - Metals in human placenta: focus on the effects of cadmium on steroid hormones and
      leptin.
AB  - Cadmium and other metallic ions can act as metalloestrogens and endocrine
      disruptors of reproductive tissues and fetal development in mammals, including
      humans. The detrimental effects occur with respect to the synthesis of both
      steroid and polypeptide hormones in the placenta. Leptin is produced by the
      trophoblast and may regulate fetal organogenesis and development. In human term
      placentas, concentrations of toxic metals and their effects on steroidogenesis
      were assessed in healthy parturients (109 non-smokers and 99 smokers) in relation
      to tobacco smoking. Trace elements (cadmium, lead, iron, zinc and copper) were
      analyzed in placentas using atomic absorption spectroscopy, and steroid hormones
      (progesterone and estradiol) were assayed in placental samples by an enzyme
      immunometric method. Cadmium concentrations were doubled in placentas of smokers
      as compared with non-smokers, and placental lead and zinc concentrations
      increased significantly. Placental concentrations of iron, copper, progesterone
      and estradiol did not differ. In addition, human trophoblast cells were co
      cultured with 0, 5, 10 or 20 microm CdCl(2) for 96 h and leptin mRNA assessed by
      quantitative polymerase chain reaction. Leptin mRNA declined dose-responsively as
      a result of CdCl(2) exposure. Collectively, the results confirm that human
      placental tissue offers a unique opportunity to biomonitor cadmium exposure in
      both the maternal and the internal fetal environments. In addition, the results
      strongly suggest that cadmium may cause a decline in placental leptin synthesis,
      as we have previously shown for placental progesterone production. This may
      constitute further evidence of the endocrine-disrupting effects of cadmium, as a
      constituent of tobacco smoke, on reproduction in women.

PMID- 19847777
TI  - A novel and efficient tool for locating and characterizing protein cavities and
      binding sites.
AB  - Systematic investigation of a protein and its binding site characteristics are
      crucial for designing small molecules that modulate protein functions. However,
      fundamental uncertainties in binding site interactions and insufficient knowledge
      of the properties of even well-defined binding pockets can make it difficult to
      design optimal drugs. Herein, we report the development and implementation of a
      cavity detection algorithm built with HINT toolkit functions that we are naming
      Vectorial Identification of Cavity Extents (VICE). This very efficient algorithm
      is based on geometric criteria applied to simple integer grid maps. In testing,
      we carried out a systematic investigation on a very diverse data set of proteins
      and protein-protein/protein-polynucleotide complexes for locating and
      characterizing the indentations, cavities, pockets, grooves, channels, and
      surface regions. Additionally, we evaluated a curated data set of unbound
      proteins for which a ligand-bound protein structures are also known; here the
      VICE algorithm located the actual ligand in the largest cavity in 83% of the
      cases and in one of the three largest in 90% of the cases. An interactive front
      end provides a quick and simple procedure for locating, displaying and
      manipulating cavities in these structures. Information describing the cavity,
      including its volume and surface area metrics, and lists of atoms, residues,
      and/or chains lining the binding pocket, can be easily obtained and analyzed. For
      example, the relative cross-sectional surface area (to total surface area) of
      cavity openings in well-enclosed cavities is 0.06 +/- 0.04 and in surface clefts
      or crevices is 0.25 +/- 0.09. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

PMID- 19847778
TI  - Supported liquid extraction in combination with LC-MS/MS for high-throughput
      quantitative analysis of hydrocortisone in mouse serum.
AB  - A high-throughput LC-MS/MS bioanalytical method was developed and validated for
      the determination of hydrocortisone in mouse serum via supported liquid
      extraction (SLE) in a 96-well plate format. Although sample extracts from SLE
      result in similar matrix effects compared with conventional liquid-liquid
      extraction (LLE), greater analyte extraction recovery and much higher analysis
      throughput for the quantitative analysis of hydrocortisone in mouse serum were
      obtained. The current LC-MS/MS method was validated for a concentration range of
      2.00-2000 ng/mL for hydrocortisone using a 0.100 mL volume of mouse serum. The
      intra- and inter-day precision and accuracy of the quality control samples at
      low, medium and high concentration levels showed < or =12.9% CV and -3.4-6.2%
      bias for the analyte in mouse serum.

PMID- 19847779
TI  - An optimum strategy for solution chemistry using semiempirical molecular orbital
      method: importance of description of charge distribution.
AB  - For the purpose to execute direct dynamics calculation in solution chemistry, we
      propose an optimum strategy for solution chemistry using semiempirical molecular
      orbital (MO) method with neglect of diatomic differential overlap (NDDO)
      approximation with specific solution reaction parameters (SSRP), i.e., the NDDO
      SSRP method. In this strategy, the empirical parameters of the semi-empirical MO
      method were optimized individually for target molecule or ion by reference to the
      ab initio MO calculation data for many configurations on the potential energy
      surface near the reaction path. For demonstration, the NDDO-SSRP method was
      applied to two molecules and two ions (OH(-), H(2)O, NH(3), NH(4)(+)) at their
      equilibrium states in aqueous solution, respectively. Accordingly, it was
      verified that both the potential energy surface and the charge distribution of
      these solutes in aqueous solution are dramatically improved to reproduce
      themselves accurately at ab initio MO calculation level. In conclusion, it is
      expected that the NDDO-SSRP method should become quite useful for dynamic and
      statistical applications to chemical reaction systems in solution.

PMID- 19847780
TI  - Efficient nonbonded interactions for molecular dynamics on a graphics processing
      unit.
AB  - We describe an algorithm for computing nonbonded interactions with cutoffs on a
      graphics processing unit. We have incorporated it into OpenMM, a library for
      performing molecular simulations on high-performance computer architectures. We
      benchmark it on a variety of systems including boxes of water molecules, proteins
      in explicit solvent, a lipid bilayer, and proteins with implicit solvent. The
      results demonstrate that its performance scales linearly with the number of atoms
      over a wide range of system sizes, while being significantly faster than other
      published algorithms.

PMID- 19847781
TI  - In silico prediction and screening of gamma-secretase inhibitors by molecular
      descriptors and machine learning methods.
AB  - Gamma-secretase inhibitors have been explored for the prevention and treatment of
      Alzheimer's disease (AD). Methods for prediction and screening of gamma-secretase
      inhibitors are highly desired for facilitating the design of novel therapeutic
      agents against AD, especially when incomplete knowledge about the mechanism and
      three-dimensional structure of gamma-secretase. We explored two machine learning
      methods, support vector machine (SVM) and random forest (RF), to develop models
      for predicting gamma-secretase inhibitors of diverse structures. Quantitative
      analysis of the receiver operating characteristic (ROC) curve was performed to
      further examine and optimize the models. Especially, the Youden index (YI) was
      initially introduced into the ROC curve of RF so as to obtain an optimal
      threshold of probability for prediction. The developed models were validated by
      an external testing set with the prediction accuracies of SVM and RF 96.48 and
      98.83% for gamma-secretase inhibitors and 98.18 and 99.27% for noninhibitors,
      respectively. The different feature selection methods were used to extract the
      physicochemical features most relevant to gamma-secretase inhibition. To the best
      of our knowledge, the RF model developed in this work is the first model with a
      broad applicability domain, based on which the virtual screening of gamma
      secretase inhibitors against the ZINC database was performed, resulting in 368
      potential hit candidates.

PMID- 19847782
TI  - Temperature dependence of structure and dynamics of the hydrated Ca2+ ion
      according to ab initio quantum mechanical charge field and classical molecular
      dynamics.
AB  - Simulations using ab initio quantum mechanical charge field molecular dynamics
      (QMCF MD) and classical molecular dynamics using two-body and three-body
      potentials were performed to investigate the hydration of the Ca(2+) ion at
      different temperatures. Results from the simulations demonstrate significant
      effects of temperature on solution dynamics and the corresponding composition and
      structure of hydrated Ca(2+). Substantial increase in ligand exchange events was
      observed in going from 273.15 K to 368.15 K, resulting in a redistribution of
      coordination numbers to lower values. The effect of temperature is also visible
      in a red-shift of the ion-oxygen stretching frequencies, reflecting weakened
      ligand binding. Even the moderate increase from ambient to body temperature leads
      to significant changes in the properties of Ca(2+) in aqueous environment.

PMID- 19847783
TI  - Multicanonical ab inito QM/MM molecular dynamics simulation of a peptide in an
      aqueous environment.
AB  - We developed a multicanonical ab initio QM/MM molecular dynamics simulation
      method to enhance conformational sampling of biomolecules in an aqueous
      environment. We applied this method to an alanine dipeptide immersed in a sphere
      of explicit water molecules. The peptide and the water molecules were treated by
      the QM method at the HF/3-21G level and by the MM method, respectively. The van
      der Waals interactions between the peptide and the water molecules were
      calculated at the MM level, while the electrostatic interaction terms between
      them were incorporated into the QM Hamiltonian to account for the effect of the
      solvent on the electronic structure of the peptide. The simulation was performed
      for 1 ns, and a free-energy map was calculated with respect to the peptide
      conformation. All the conformations (C(5), P(II), C(7eq), and alpha(R)) that have
      been experimentally suggested to exist in solution formed basins on the free
      energy surface. Analysis of the water distribution revealed that the alpha(R)
      conformation was stabilized by the interaction between the large electric dipole
      moments of this peptide conformation and the water electric dipole moments,
      whereas the P(II) conformation was stabilized by the formation of characteristic
      hydrogen bonds with the water molecules.

PMID- 19847784
TI  - Theoretical study on HBO+ and HOB+ cations using multiconfiguration second-order
      perturbation theory.
AB  - The HBO(+) and HOB(+) cations have been reinvestigated using the CASSCF and
      CASPT2 methods in conjunction with the contracted atomic natural orbital (ANO)
      basis sets. The geometries of all stationary points in the potential energy
      surfaces were optimized at the CASSCF/ANO and CASPT2/ANO levels. The ground and
      the first excited states of HBO(+) are predicted to be X(2)Pi and A(2)Sigma(+)
      states, respectively. It was predicted that the ground state of HOB(+) is
      X(2)Sigma(+) state. The A(2)Pi state of HOB(+) has unique imaginary frequency. A
      bending local minimum M1 was found for the first time along the 1(2)A'' potential
      energy surface and the A(2)Pi state of HOB(+) should be the transition state of
      the isomerization reactions for M1<--> M1. The CASPT2/ANO potential energy curves
      (PECs) of isomerization reactions were calculated as functions of the HBO bond
      angle. Many of the CASSCF and CASPT2 calculated results were different from the
      previously published QCISD(T) results.

PMID- 19847785
TI  - A compound QM/MM procedure: comparative performance on a pyruvate formate-lyase
      model system.
AB  - We present an ONIOM(G3:MM) method as an example of a technique capable of
      producing chemical accuracy in the quantum mechanical (QM) treatment with a
      molecular mechanical description context. By applying the method to small model
      systems, in which we are also able to calculate the pure QM G3-type results, it
      is possible to establish the reliability of the method as it applies to
      evaluating reaction mechanisms. By choosing small model systems that are relevant
      to the substrate mechanism of pyruvate formate-lyase, we are also able to discuss
      the inhibitory effect of oxamate and the relevance of an alternative H
      abstraction mechanism in that context.

PMID- 19847786
TI  - Associative recognition and the hippocampus: differential effects of hippocampal
      lesions on object-place, object-context and object-place-context memory.
AB  - The hippocampus is thought to be required for the associative recognition of
      objects together with the spatial or temporal contexts in which they occur.
      However, recent data showing that rats with fornix lesions perform as well as
      controls in an object-place task, while being impaired on an object-place-context
      task (Eacott and Norman (2004) J Neurosci 24:1948-1953), suggest that not all
      forms of context-dependent associative recognition depend on the integrity of the
      hippocampus. To examine the role of the hippocampus in context-dependent
      recognition directly, the present study tested the effects of large, selective,
      bilateral hippocampus lesions in rats on performance of a series of spontaneous
      recognition memory tasks: object recognition, object-place recognition, object
      context recognition and object-place-context recognition. Consistent with the
      effects of fornix lesions, animals with hippocampus lesions were impaired only on
      the object-place-context task. These data confirm that not all forms of context
      dependent associative recognition are mediated by the hippocampus. Subsequent
      experiments suggested that the object-place task does not require an allocentric
      representation of space, which could account for the lack of impairment following
      hippocampus lesions. Importantly, as the object-place-context task has similar
      spatial requirements, the selective deficit in object-place-context recognition
      suggests that this task requires hippocampus-dependent neural processes distinct
      from those required for allocentric spatial memory, or for object memory, object
      place memory or object-context memory. Two possibilities are that object, place,
      and context information converge only in the hippocampus, or that recognition of
      integrated object-place-context information requires a hippocampus-dependent mode
      of retrieval, such as recollection.

PMID- 19847788
TI  - BAK1 gene variation and abdominal aortic aneurysms-variants are likely due to
      sequencing of a processed gene on chromosome 20.

PMID- 19847787
TI  - Protective effect of rosmarinic acid on V79 cells evaluated by the micronucleus
      and comet assays.
AB  - Rosmarinic acid (RA) is a naturally occurring phenolic compound, which
      contributes to the beneficial and health-promoting effects of herbs, spices and
      medicinal plants. RA has shown several biological activities, such as
      hepatoprotective, anti-inflammatory, antiangiogenic, antitumor, antidepressant,
      antineurodegenerative, HIV-1 inhibitory and antioxidant effects. The aim of this
      study was to investigate the ability of RA to prevent chemically induced
      chromosome breakage or loss and primary DNA damage using the micronucleus and
      comet assays with V79 cells, respectively. The chemotherapeutic agent doxorubicin
      (DXR; 0.5 microg ml(-1)) was used as the DNA-damaging agent. The cultures were
      treated with different concentrations of RA (0.28, 0.56 and 1.12 mm) alone or in
      combination with DXR. The results showed that RA exerted no genotoxic effect, but
      significantly reduced the frequency of micronuclei and the extent of DNA damage
      induced by DXR at the three concentrations tested. The antioxidant activity of RA
      might be involved in the reduction of DXR-induced DNA damage observed in the
      present study.

PMID- 19847789
TI  - Common pathological mutations in PQBP1 induce nonsense-mediated mRNA decay and
      enhance exclusion of the mutant exon.
AB  - The polyglutamine binding protein 1 (PQBP1) gene plays an important role in X
      linked mental retardation (XLMR). Nine of the thirteen PQBP1 mutations known to
      date affect the AG hexamer in exon 4 and cause frameshifts introducing premature
      termination codons (PTCs). However, the phenotype in this group of patients is
      variable. To investigate the pathology of these PQBP1 mutations, we evaluated
      their consequences on mRNA and protein expression. RT-PCRs revealed mutation
      specific reduction of PQBP1 mRNAs carrying the PTCs that can be partially
      restored by blocking translation, thus indicating a role for the nonsense
      mediated mRNA decay pathway. In addition, these mutations resulted in altered
      levels of PQBP1 transcripts that skipped exon 4, probably as a result of altering
      important splicing motifs via nonsense-associated altered splicing (NAS). This
      hypothesis is supported by transfection experiments using wild-type and mutant
      PQBP1 minigenes. Moreover, we show that a truncated PQBP1 protein is indeed
      present in the patients. Remarkably, patients with insertion/deletion mutations
      in the AG hexamer express significantly increased levels of a PQBP1 isoform,
      which is very likely encoded by the transcripts without exon 4, confirming the
      findings at the mRNA level. Our study provides significant insight into the early
      events contributing to the pathogenesis of the PQBP1 related XLMR disease.

PMID- 19847791
TI  - ADAMTS13 mutations and polymorphisms in congenital thrombotic thrombocytopenic
      purpura.
AB  - Congenital thrombotic thrombocytopenic purpura (TTP) (also known as Upshaw
      Schulman syndrome, USS) is a rare, life-threatening disease characterized by
      thrombocytopenia and microangiopathic hemolytic anemia, associated with the
      deficiency of the von Willebrand factor-cleaving protease (ADAMTS13) due to
      mutations in the corresponding gene. The spectrum of clinical phenotype in
      congenital TTP is wide, encompassing neonatal-onset disease and adult-onset
      disease, forms with a single disease episode and chronic-relapsing forms. We
      review ADAMTS13 gene variants associated with inherited ADAMTS13 deficiency and
      congenital TTP. To date, 76 mutations of ADAMTS13 are reported in the literature.
      Missense mutations, which constitute nearly 60% of ADAMTS13 mutations,
      preferentially localize in the 5'-half of the gene encoding the N-terminal half
      of the protein, where the domains that are indispensable for ADAMTS13 catalytic
      function are situated. In vitro expression studies in cell cultures have shown
      that defects in protein secretion and catalytic activity are the main mechanisms
      responsible for the deficiency of ADAMTS13 in congenital TTP patients. Even if
      data from the literature suggest the existence of genotype-phenotype
      correlations, a clear relationship between the type and the effect of ADAMTS13
      genetic defects with disease manifestations remains to be established.

PMID- 19847790
TI  - Allelic imbalance (AI) identifies novel tissue-specific cis-regulatory variation
      for human UGT2B15.
AB  - Allelic imbalance (AI) is a powerful tool to identify cis-regulatory variation
      for gene expression. UGT2B15 is an important enzyme involved in the metabolism of
      multiple endobiotics and xenobiotics. In this study, we measured the relative
      expression of two alleles at this gene by using SNP rs1902023:G>T. An excess of
      the G over the T allele was consistently observed in liver (P<0.001), but not in
      breast (P=0.06) samples, suggesting that SNPs in strong linkage disequilibrium
      with G253T regulate UGT2B15 expression in liver. Seven such SNPs were identified
      by resequencing the promoter and exon 1, which define two distinct haplotypes.
      Reporter gene assays confirmed that one haplotype displayed approximately 20%
      higher promoter activity compared to the other major haplotype in liver HepG2
      (P<0.001), but not in breast MCF-7 (P=0.540) cells. Reporter gene assays with
      additional constructs pointed to rs34010522:G>T and rs35513228:C>T as the cis
      regulatory variants; both SNPs were also evaluated in LNCaP and Caco-2 cells. By
      ChIP, we showed that the transcription factor Nrf2 binds to the region spanning
      rs34010522:G>T in all four cell lines. Our results provide a good example for how
      AI can be used to identify cis-regulatory variation and gain insights into the
      tissue specific regulation of gene expression.

PMID- 19847792
TI  - A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS)
      causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie
      Haas type polysyndactyly and preaxial polydactyly (PPD) with or without
      triphalangeal thumb.
AB  - Werner mesomelic syndrome (WMS) is an autosomal dominant disorder with unknown
      molecular etiology characterized by hypo- or aplasia of the tibiae in addition to
      the preaxial polydactyly (PPD) of the hands and feet and/or five-fingered hand
      with absence of thumbs. We show that point mutations of a specific nucleotide
      within the sonic hedgehog (SHH) regulatory region (ZRS) cause WMS. In a
      previously unpublished WMS family, we identified the causative G>A transition at
      position 404 of the ZRS, and in six affected family members of a second WMS
      family we found a 404G>C mutation of the ZRS. The 404G>A ZRS mutation is known as
      the "Cuban mutation" of PPD type II (PPD2). Interestingly, the index patient of
      that family had tibial hypoplasia as well. These data provide the first evidence
      that WMS is caused by a specific ZRS mutation, which leads to strong ectopic SHH
      expression. In contrast, we show that complete duplications of the ZRS region
      lead to type Haas polysyndactyly or triphalangeal thumb-polysyndactyly syndrome,
      but do not affect lower limb development. We suggest the term "ZRS-associated
      syndromes" and a clinical subclassification for the continuum of limb
      malformations caused by different molecular alterations of the ZRS.

PMID- 19847793
TI  - Clinically reported heterozygous mutations in the PINK1 kinase domain exert a
      gene dosage effect.
AB  - Mutations in the gene encoding phosphatase and tensin homolog (PTEN)-induced
      kinase 1 (PINK1) have been associated with the loss of dopaminergic neurons
      characteristic of familial and sporadic Parkinson disease. We developed an in
      vitro system of stable human dopaminergic neuronal cell lines coexpressing an
      equivalent copy of normal and mutant PINK1 to simulate "heterozygous" and
      "homozygous" states in patients. Mutants in the N-terminus, C-terminus, and
      kinase domain were generated and cloned into a two-gene mammalian expression
      vector to generate stable mammalian expression cell lines producing an equivalent
      copy number of wild-type/mutant PINK1. The cell lines were subjected to oxidative
      stress and the rate of apoptosis and change in mitochondrial membrane potential
      (DeltaPsi(m)) were assessed. Cell lines expressing kinase and C-terminus mutants
      exhibited a greater rate of apoptosis and decrease in DeltaPsi(m), and increased
      time-dependent cell loss when subjected to oxidative stress compared to the wild
      type. Cell lines expressing two copies of kinase mutants exhibited a greater
      apoptosis rate and DeltaPsi(m) decrease than those expressing one copy of the
      mutant. In time-dependent experiments, there was a significant difference between
      "homozygous," "heterozygous," and wild-type cell lines, with decreasing cell
      survival in cell lines expressing mutant copies of PINK1 compared to the wild
      type. We provided the first experimental evidence that clinically reported PINK1
      heterozygous mutations exert a gene dosage effect, suggesting that
      haploinsufficiency of PINK1 is the most likely mechanism that increased the
      susceptibility to dopaminergic cellular loss.

PMID- 19847794
TI  - Proteomic analysis of novel Cry1Ac binding proteins in Helicoverpa armigera
      (Hubner).
AB  - Aminopeptidase N (APN) and cadherin-like proteins have been previously identified
      as Cry1Ac-binding proteins in Helicoverpa armigera (Hubner). In this study, a
      proteomic approach was used to identify novel Cry1Ac-binding proteins in H.
      armigera. Brush border membrane vesicles (BBMV) of H. armigera were extracted and
      separated by two-dimensional gel electrophoresis (2-DE). Cry1Ac-binding proteins
      were detected using antisera against Cry1Ac. Peptide mass fingerprinting (PMF)
      was used to identify Cry1Ac-binding proteins. In total, four proteins were
      identified as candidate Cry1Ac-binding proteins in H. armigera: vacuolar ATP
      synthase (V-ATPase) subunit B, actin, heat shock cognate protein (HSCP), and a
      novel protein.

PMID- 19847795
TI  - Meta-analysis of genome-wide association studies: no efficiency gain in using
      individual participant data.
AB  - To identify genetic variants with modest effects on complex human diseases, a
      growing number of networks or consortia are created for sharing data from
      multiple genome-wide association studies on the same disease or related
      disorders. A central question in this enterprise is whether to obtain summary
      results or individual participant data from relevant studies. We show
      theoretically and numerically that meta-analysis of summary results is
      statistically as efficient as joint analysis of individual participant data
      (provided that both analyses are performed properly under the same modeling
      assumptions). We illustrate this equivalence with case-control data from the
      Finland-United States Investigation of NIDDM Genetics (FUSION) study. Collating
      only summary results will increase the number and representativeness of available
      studies, simplify data collection and analysis, reduce resource utilization, and
      accelerate discovery.

PMID- 19847797
TI  - Biophotonics and Regenerative Medicine--ideal partners for research in the 21(st)
      Century.

PMID- 19847796
TI  - Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in
      German and Italian familial breast cancer cases.
AB  - Recently, the SNPs rs11614913 in hsa-mir-196a2 and rs3746444 in hsa-mir-499 were
      reported to be associated with increased breast cancer risk, and the SNP
      rs2910164 in hsa-mir-146a was shown to have an effect on age of breast cancer
      diagnosis. In order to further investigate the effect of these SNPs, we genotyped
      a total of 1894 breast cancer cases negative for disease-causing mutations or
      unclassified variants in BRCA1 and BRCA2, and 2760 controls from Germany and
      Italy. We compared the genotype and allele frequencies of rs2910164, rs11614913
      and rs3746444 in cases versus controls of the German and Italian series, and of
      the two series combined; we also investigated the effect of the three SNPs on age
      at breast cancer diagnosis. None of the performed analyses showed statistically
      significant results. In conclusion, our data suggested lack of association
      between SNPs rs2910164, rs11614913 and rs3746444 and breast cancer risk, or age
      at breast cancer onset.

PMID- 19847800
TI  - In vivo imaging of hematopoietic stem cells and their microenvironment.
AB  - In this review we provide a description of the basic concepts and paradigms
      currently constituting the foundations of adult stem cell biology, and discuss
      the role that live imaging techniques have in the development of the field. We
      focus on live imaging of hematopoietic stem cells (HSCs) as the basic biology and
      clinical applications of HSCs have historically been at the forefront of the stem
      cell field, and HSC are the first mammalian tissue stem cells to be visualized in
      vivo using advanced light microscopy techniques. We outline the current technical
      challenges that remain to be overcome before stem cells and their niche can be
      more fully characterized using the live imaging technology.

PMID- 19847801
TI  - In vivo optical monitoring of tissue pathologies and diseases with vibrational
      contrast.
AB  - Studies of tissue remodeling require in vivo imaging techniques that are as
      minimally invasive as possible to avoid microenvironment perturbations. To this
      end, spontaneous Raman techniques have been used but low signals have limited
      their application mostly to point spectroscopy measurements. Novel Raman-based
      techniques such as coherent and stimulated Raman scattering can overcome this
      limitation. This manuscript discusses imaging and spectroscopy applications with
      Raman-based contrast for in vivo tissue monitoring, and how these can be combined
      into spectral imaging.

PMID- 19847802
TI  - Regulation of stemness and stem cell niche of mesenchymal stem cells:
      implications in tumorigenesis and metastasis.
AB  - Human mesenchymal stem cells (MSCs) derived from adult tissues have been
      considered a candidate cell type for cell-based tissue engineering and
      regenerative medicine. These multipotent cells have the ability to differentiate
      along several mesenchymal lineages and possibly along non-mesenchymal lineages.
      MSCs possess considerable immunosuppressive properties that can influence the
      surrounding tissue positively during regeneration, but perhaps negatively towards
      the pathogenesis of cancer and metastasis. The balance between the naive stem
      state and differentiation is highly dependent on the stem cell niche.
      Identification of stem cell niche components has helped to elucidate the
      mechanisms of stem cell maintenance and differentiation. Ultimately, the fate of
      stem cells is dictated by their microenvironment. In this review, we describe the
      identification and characterization of bone marrow-derived MSCs, the properties
      of the bone marrow stem cell niche, and the possibility and likelihood of MSC
      involvement in cancer progression and metastasis.

PMID- 19847803
TI  - The role of Runx1/AML1 and Evi-1 in the regulation of hematopoietic stem cells.
AB  - Lineage-specific transcription factors must be precisely regulated during stem
      cell self-renewal and lineage commitment decisions. The role of specific
      transcription factors in hematopoietic stem cell (HSC) fate decisions has derived
      largely from genetic strategies, primarily gene-targeting and transgenic or
      retroviral overexpression experiments. From the previous experimental results,
      several transcription factors have been found to play critical roles in HSC
      physiology. Among them, we focus two transcription factors, Runx1/AML1 and Evi-1,
      in this review. During embryogenesis, both Runx1 and Evi-1 are essential for HSCs
      whereas in the adult, Runx1 and Evi-1 regulate HSCs negatively and positively,
      respectively.

PMID- 19847805
TI  - Separation of inorganic and small organic anions by CE using phosphonium-based
      mono- and dicationic reagents.
AB  - The separation of relatively small, fast-migrating anions by CE is not possible
      under standard conditions with cathodic EOF of relatively high velocity.
      Therefore, separation approaches for these analytes usually include suppression
      or reversal of the EOF using various cationic additives to the BGE or covalent
      coating of the capillary walls. In this study, novel phosphonium-based mono- and
      dicationic reagents (originally synthesized as ionic liquids) were evaluated as
      additives to the BGE for the separation of inorganic and small organic anions.
      The effects of these reagents on the EOF and their interactions with anionic
      analytes were compared. The effects of the additive's structure and concentration
      as well as the separation buffer pH have been studied. Propane-1,3
      bis(tripropylphosphonium) fluoride proved to be the most effective additive, as
      it suppressed the EOF in the system and enabled remarkable manipulation of
      separation selectivity. A method for fast, reliable, and efficient separation of
      six inorganic and seven organic anions within 7 min time was developed using
      propane-1,3-bis(tripropylphosphonium) fluoride as an additive to the separation
      buffer.

PMID- 19847804
TI  - Sterility testing by CE: a comparison of online preconcentration approaches in
      capillaries with greater internal diameters.
AB  - Detection of microbial contamination is of critical importance in the medical and
      the food industry. Rapid tests for the absence or presence of viable
      microorganisms are in urgent demand. CE is a modern analytical technique that can
      be adapted for rapid screening of microbial contamination. However, the small
      dimensions of capillaries allow the introduction of only a small fraction of the
      sample, which can be problematic when examining large samples. In this article,
      we examine the possibilities of introducing larger sample volumes using
      capillaries with greater id together with different stacking techniques. The use
      of 0.32 mm id capillary and the injection of 60% of the capillary volume led to
      approximately 120-fold improvement of the injected sample volume over the
      classical injection 5% of a 0.10-mm id capillary. The setup we described opens
      new possibilities in sterility testing using CE.

PMID- 19847806
TI  - Thrombin stimulates RPE cell proliferation by promoting c-Fos-mediated cyclin D1
      expression.
AB  - The retinal pigment epithelium (RPE) plays an essential role in the maintenance
      and normal functioning of the neural retina. Alterations in RPE function are
      involved in several ocular pathologies involving the breakdown of the blood
      retina barrier (BRB), which exposes RPE to serum components, thrombin among them.
      Our previous work has shown that thrombin stimulates the proliferation of RPE
      cells. We here analyzed the molecular pathways leading to this outcome, in order
      to support thrombin involvement in proliferative vitreoretinopathy (PVR), a major
      cause of retinal surgery failure. We demonstrated that thrombin activation of PAR
      1 promotes cyclin D1 expression at the transcriptional level by stimulating c-Fos
      expression, mediated by PI3K, MAPK ERK1/2, and conventional PKC activity. Our
      results show that ERK activation is necessary but not sufficient for the
      induction of cyclin D1 expression and proliferation, since the inhibition of PI3K
      or cPKC prevents this outcome. Analysis of thrombin-activated PAR-1 downstream
      effectors demonstrated that c-Fos expression by the sustained activation of ERK
      and c-fos transcription triggers the expression and nuclear translocation of
      cyclin D1, a key regulator of cell cycle G1/S phase progression leading to
      proliferation. Evidence here provided contributes to the understanding of the
      mechanisms involved in proliferative eye diseases and enhances the possibility of
      controlling pathologies such as proliferative PVR, which eventually lead to
      blindness.

PMID- 19847807
TI  - Molecular mechanism underlying muscle mass retention in hibernating bats: role of
      periodic arousal.
AB  - Hibernators like bats show only marginal muscle atrophy during prolonged
      hibernation. The current study was designed to test the hypothesis that
      hibernators use periodic arousal to increase protein anabolism that compensates
      for the continuous muscle proteolysis during disuse. To test this hypothesis, we
      investigated the effects of 3-month hibernation (HB) and 7-day post-arousal
      torpor (TP) followed by re-arousal (RA) on signaling activities in the pectoral
      muscles of summer-active (SA) and dormant Murina leucogaster bats. The bats did
      not lose muscle mass relative to body mass during the HB or TP-to-RA period. For
      the first 30-min following arousal, the peak amplitude and frequency of
      electromyographic spikes increased 3.1- and 1.4-fold, respectively, indicating
      massive myofiber recruitment and elevated motor signaling during shivering.
      Immunoblot analyses of whole-tissue lysates revealed several principal outcomes:
      (1) for the 3-month HB, the phosphorylation levels of Akt1 (p-Akt1) and p-mTOR
      decreased significantly compared to SA bats, but p-FoxO1 levels remained
      unaltered; (2) for the TP-to-RA period, p-Akt1 and p-FoxO1 varied little, while p
      mTOR showed biphasic oscillation; (3) proteolytic signals (i.e., atrogin-1,
      MuRF1, Skp2 and calpain-1) remained constant during the HB and TP-to-RA period.
      These results suggest that the resistive properties of torpid bat muscle against
      atrophy might be attained primarily by relatively constant proteolysis in
      combination with oscillatory anabolic activity (e.g., p-mTOR) corresponding to
      the frequency of arousals occurring throughout hibernation.

PMID- 19847808
TI  - A locus on chromosome 8 controlling tumor regionality-a new type of tumor
      diversity in the mouse lung.
AB  - Regional specificity of lung tumor formation has rarely been studied in mouse or
      human. By using crosses of strains semi-congenic for lung cancer susceptibility
      locus Sluc20, we have analyzed the genetic influences of Sluc20 and 5 other loci
      on tumor regionality in the mouse lung. We have mapped Sluc20 to a 27.92-MB
      proximal region of chromosome 8 and found that it controls the number and load of
      only those tumors that surround or are directly adjacent to the bronchi or
      bronchioli (peribronchial tumors). These tumors lie outside the bronchial
      basement membrane and tend to reach a larger size than the tumors at other
      locations in the lung. Similar to tumors of alveolar lineage at other locations,
      peribronchial tumors stain with SP-C but not CC10 antibody. The effects of Sluc20
      alleles are additive because the number of peribronchial tumors in heterozygotes
      is intermediate. These findings show that tumor regionality in the mouse lung,
      which represents a novel level of lung tumor heterogeneity, is under specific
      genetic control. The identification of genes controlling lung tumor regionality
      will provide novel insights into the biology of lung tumors and potentially
      improve the possibilities of individualized prognosis and treatment in human lung
      cancer.

PMID- 19847809
TI  - Letter in response to "Identifying Lynch syndrome" by de la Chapelle et al.

PMID- 19847810
TI  - Frequent promoter hypermethylation of Wnt pathway inhibitor genes in malignant
      astrocytic gliomas.
AB  - Aberrant activation of wingless (Wnt) signaling is involved in the pathogenesis
      of various cancers. Recent studies suggested a role of Wnt signaling in gliomas,
      the most common primary brain tumors. We investigated 70 gliomas of different
      malignancy grades for promoter hypermethylation in 8 genes encoding members of
      the secreted frizzled-related protein (SFRP1, SFRP2, SFRP4, SFRP5), dickkopf
      (DKK1, DKK3) and naked (NKD1, NKD2) families of Wnt pathway inhibitors. All
      tumors were additionally analyzed for mutations in exon 3 of the beta-catenin
      gene (CTNNB1). While none of the tumors carried CTNNB1 mutations, we found
      frequent promoter hypermethylation of Wnt pathway inhibitor genes, with at least
      one of these genes being hypermethylated in 6 of 16 diffuse astrocytomas (38%), 4
      of 14 anaplastic astrocytomas (29%), 7 of 10 secondary glioblastomas (70%) and 23
      of 30 primary glioblastomas (77%). Glioblastomas often demonstrated
      hypermethylation of 2 or more analyzed genes. Hypermethylation of SFRP1, SFRP2
      and NKD2 each occurred in more than 40% of the primary glioblastomas, while DKK1
      hypermethylation was found in 50% of secondary glioblastomas. Treatment of SFRP1
      , SFRP5-, DKK1-, DKK3-, NKD1- and NKD2-hypermethylated U87-MG glioblastoma cells
      with 5-aza-2'-deoxycytidine and trichostatin A resulted in increased expression
      of each gene. Furthermore, SFRP1-hypermethylated gliomas showed significantly
      lower expression of the respective transcripts when compared with unmethylated
      tumors. Taken together, our results suggest an important role of epigenetic
      silencing of Wnt pathway inhibitor genes in astrocytic gliomas, in particular, in
      glioblastomas, with distinct patterns of hypermethylated genes distinguishing
      primary from secondary glioblastomas.

PMID- 19847811
TI  - The role of the intravascular microenvironment in spontaneous metastasis
      development.
AB  - Metastasis is primarily responsible for the morbidity and mortality of cancer.
      Improved therapeutic outcomes and prognosis depend on improved understanding of
      mechanisms regulating the establishment of early metastasis. In this study, use
      of green fluorescent protein (GFP)-expressing PC-3 orthotopic model of human
      prostate cancer and two complementary fluorescence in vivo imaging systems
      (Olympus OV100 and VisEn FMT) allowed for the first time real-time
      characterization of cancer cell-endothelium interactions during spontaneous
      metastatic colonization of the liver and lung in live mice. We observed that
      prior to the detection of extra-vascular metastases, GFP-expressing PC-3 cancer
      cells resided initially inside the blood vessels of the liver and the lung, where
      they proliferated and expressed Ki-67 and exhibited matrix metalloprotenases
      (MMP) activity. Thus, the intravascular cancer cells produced their own
      microenvironment, where they could continue to proliferate. Extravasation
      occurred earlier in the lung than in the liver. Our results demonstrate that the
      intravascular microenvironment is a critical staging area for the development of
      metastasis that later can invade the parenchyma. Intravascular tumor cells may
      represent a therapeutic target to inhibit the development of extravascular
      metastases. Therefore, this imageable model of intravascular metastasis may be
      used for evaluation of novel anti-metastatic agents.

PMID- 19847812
TI  - Expression and prognostic significance of iNOS in uveal melanoma.
AB  - Uveal melanoma (UM) is the most common primary intraocular tumor in adults.
      Disease metastasis occurs in half of the patients and is uniformly fatal despite
      systemic therapy. Inducible nitric oxide synthase (iNOS) is associated with
      disease progression in various malignancies including cutaneous melanoma. In this
      retrospective cohort, we examined the prognostic value of iNOS in UM by
      performing immunohistochemistry on paraffin-embedded sections of primary tumors
      (90 patients) and matched primary and metastatic hepatic tumors (19 patients)
      with complete histopathological and clinical data. We show that iNOS is expressed
      in UM (57% of the patients) and high iNOS levels significantly (p = 0.04; hazard
      ratio (HR) = 2.3) predict disease-specific survival (DSS) as assessed by Kaplan
      Meier analysis and univariate Cox's proportional hazards regression model.
      Furthermore, high iNOS expression in the UM primary tissue was significantly
      associated with metastatic disease and vice versa. Expression of iNOS in hepatic
      metastases significantly (p = 0.02) predicted a shortened survival as assessed by
      Kaplan-Meier analysis. However, iNOS did not appear to be a significant (p =
      0.16; HR = 1.9) factor in the multivariate Cox's regression analysis performed
      together with the clinical parameters tumor diameter, tumor cell type, and tumor
      location in which only tumor diameter predicted DSS. In conclusion, iNOS predicts
      DSS in UM and may play a role in disease progression but it is not an independent
      prognostic factor.

PMID- 19847813
TI  - Complementary use of fluorescence and magnetic resonance imaging of metastatic
      esophageal cancer in a novel orthotopic mouse model.
AB  - We describe the development of an aggressive orthotopic metastatic model of
      esophageal cancer, which is visualized in real time with combined magnetic
      resonance imaging (MRI) and fluorescence imaging. The aim of the study was to
      describe the development of a novel model of metastatic tumor disease of
      esophageal carcinoma and use this model to evaluate fluorescence and MRI in early
      detection of local and metastatic disease. The human esophageal adenocarcinoma
      cell line PT1590 was stably transfected with green fluorescent protein (GFP).
      Nude mice were orthotopically implanted with PT1590-GFP cells. Orthotopic tumor
      growth as well as metastatic spread was examined by fluorescence imaging and high
      resolution MRI at defined intervals after orthotopic implantation. Highly
      aggressive novel fluorescent cell lines were isolated from metastatic tissues and
      put into culture. After implantation of these cells, 100% of the animals
      developed orthotopic primary tumors. In 83% of animals, metastatic spread to
      liver, lung and lymph nodes was observed. Primary tumor growth could be
      visualized with fluorescence imaging and with MRI with high correlation between
      the 2 methods. Fluorescence imaging allows fast, sensitive, and economical
      imaging of the primary and metastatic tumor without anesthesia. With MRI,
      anatomical structures are visualized more precisely and tumors can be more
      accurately localized to specific organs. This model should prove highly useful to
      understand esophageal carcinoma and to identify novel therapeutics for this
      treatment-resistant disease.

PMID- 19847816
TI  - The fight for evolution: acceptance through pragmatism?: Evolution is framed as a
      belief, so scientists must bring it down to Earth and into the realms of public
      relevance.

PMID- 19847817
TI  - Women's narratives on experiences of work ability and functioning in
      fibromyalgia.
AB  - BACKGROUND: Fibromyalgia is a significant health problem for women of working
      age. However, little is known about the long-term effects of fibromyalgia in
      everyday life or on work ability. METHODS: A narrative interview study was
      conducted to explore the experiences of work ability and functioning of patients
      with a long history of fibromyalgia. Twenty women, aged 34-65 years, were
      purposively chosen for the interviews, to reach a wide range of patients with
      different social and professional backgrounds. RESULTS: Four types of experience
      concerning work ability were identified in the narratives: confusion, coping with
      fluctuating symptoms, being 'in between' and being over the edge of exhaustion.
      Severe pain and fatigue symptoms, combined with a demanding life situation and
      ageing, seemed to lead to substantial decrease in work ability and functioning
      over the long term. In the narratives, vocational rehabilitation or adjustments
      to work tasks were rarely seen or were started too late to be effective.
      CONCLUSIONS: Exploring the life stories of women with fibromyalgia can reveal the
      perceived causes and consequences of fibromyalgia related to work ability or
      disability, which can be utilized in developing client-centred rehabilitation
      approaches and effective interventions to support work ability and avoid
      premature retirement in fibromyalgia patients.

PMID- 19847818
TI  - Flower symmetry evolution: towards understanding the abominable mystery of
      angiosperm radiation.
AB  - Flower symmetry is considered a morphological novelty that contributed
      significantly to the rapid radiation of the angiosperms, which already puzzled
      Charles Darwin and prompted him to name this phenomenon an 'abominable mystery'.
      In 2009, the bicentenary of Darwin's birth and the 150th anniversary of the
      publication of his seminal work, 'On the Origin of Species', this question can
      now be more satisfactorily readdressed. Understanding the molecular control of
      monosymmetry formation in the model species Antirrhinum opened the path for
      comparative studies with non-model species revealing modifications of this trait.
      TCP transcription factors, named after TEOSINTE BRANCHED 1 in maize, CYCLOIDEA in
      snapdragon and PCF in rice, control flower monosymmetry development and
      contributed to establishing this trait several times independently in higher
      angiosperms. The joint advances in evolutionary and developmental plant research,
      combined in the novel research field named Evo/Devo, aim at elucidating the
      molecular mechanisms and strategies to unravel the mystery of how this diversity
      has been generated.

PMID- 19847819
TI  - Early steps in plastid evolution: current ideas and controversies.
AB  - Some nuclear-encoded proteins are imported into higher plant plastids via the
      endomembrane (EM) system. Compared with multi-protein Toc and Tic translocons
      required for most plastid protein import, the relatively uncomplicated nature of
      EM trafficking led to suggestions that it was the original transport mechanism
      for nuclear-encoded endosymbiont proteins, and critical for the early stages of
      plastid evolution. Its apparent simplicity disappears, however, when EM transport
      is considered in light of selective constraints likely encountered during the
      conversion of stable endosymbionts into fully integrated organelles. From this
      perspective it is more parsimonious to presume the early evolution of post
      translational protein import via simpler, ancestral forms of modern Toc and Tic
      plastid translocons, with EM trafficking arising later to accommodate
      glycosylation and/or protein targeting to multiple cellular locations. This
      hypothesis is supported by both empirical and comparative data, and is consistent
      with the relative paucity of EM-based transport to modern primary plastids.

PMID- 19847820
TI  - Reply to "Humans as second orangutans: sense or nonsense?".

PMID- 19847822
TI  - One-pot mechanosynthesis with three levels of molecular self-assembly:
      coordination bonds, hydrogen bonds and host-guest inclusion.
AB  - Liquid-assisted grinding (LAG) was used to combine three levels of molecular self
      assembly into a one-pot mechanochemical approach for the construction of metal
      organic materials. The approach was applied for the construction of three adducts
      of cobalt(II) dibenzoylmethanate with isonicotinamide, nicotinamide and
      imidazole, to screen for their inclusion compounds. The one-pot process consists
      of: i) The coordination-driven binding of addends to the equatorially-protected
      metal ion, resulting in "wheel-and-axle"-shaped complexes; ii) self-assembly of
      resulting complexes by way of hydrogen-bonded synthons to form metal-organic
      inclusion hosts; iii) in situ inclusion of the grinding liquid in the resulting
      host. This approach provided quantitatively and within 20 min the known inclusion
      compounds of the bis(isonicotinamide) adduct in a single synthetic step. Changing
      the liquid phase in LAG was used to explore the inclusion behaviour of new wheel
      and-axle adducts with nicotinamide and imidazole, revealing several inclusion
      compounds, as well as two polymorphs, of the bis(nicotinamide) host. Preliminary
      results suggest that one-pot LAG is superior to solution synthesis in screening
      for metal-organic inclusion compounds. The difference between the methods is
      rationalised in terms of reactant solubility and solvent competition. In contrast
      to the nicotinamide adduct, the bis(imidazole) adduct did not form inclusion
      compounds. The difference in the inclusion properties of the two adducts is
      rationalised by structural information gathered by single crystal and powder X
      ray diffraction.

PMID- 19847824
TI  - Auto-tandem catalysis: a single catalyst activating mechanistically distinct
      reactions in a single reactor.
AB  - Domino reactions have received great attention as efficient synthetic
      methodologies for the construction of structurally complex molecules from simple
      materials in a single operation. Catalysts in domino reactions have also been
      well studied. In these reactions, a catalyst activates the substrate(s) only
      once, and the structure of the product is delineated at that time. Recently, the
      new concept of "tandem catalysis" in domino reactions, in which catalyst(s)
      sequentially activate more than two mechanistically distinct reactions, has been
      proposed. Tandem catalysis is categorized into three subclasses: orthogonal-,
      auto-, and assisted-tandem catalyses. Auto-tandem catalysis is defined as a
      process in which one catalyst promotes more than two fundamentally different
      reactions in a single reactor. An overview of recent and significant achievements
      in auto-tandem catalysis is presented in this paper.

PMID- 19847823
TI  - Microwave-assisted functionalization of carbon nanostructures in ionic liquids.
AB  - The effect of microwave (MW) irradiation and ionic liquids (IL) on the
      cycloaddition of azomethine ylides to [60]fullerene has been investigated by
      screening the reaction protocol with regard to the IL medium composition, the
      applied MW power, and the simultaneous cooling of the system. [60]Fullerene
      conversion up to 98 % is achieved in 2-10 min, by using a 1:3 mixture of the IL 1
      methyl-3-n-octyl imidazolium tetrafluoroborate ([omim]BF(4)) and o
      dichlorobenzene, and an applied power as low as 12 W. The mono- versus poly
      addition selectivity to [60]fullerene can be tuned as a function of fullerene
      concentration. The reaction scope includes aliphatic, aromatic, and fluorous
      tagged (FT) derivatives. MW irradiation of IL-structured bucky gels is
      instrumental for the functionalization of single-walled carbon nanotubes (SWNTs),
      yielding group coverages of up to one functional group per 60 carbon atoms of the
      SWNT network. An improved performance is obtained in low viscosity bucky gels, in
      the order [bmim]BF(4)> [omim]BF(4)> [hvim]TF(2)N (bmim=1-methyl-3-n-butyl
      imidazolium; hvim=1-vinyl-3-n-hexadecyl imidazolium). With this protocol, the
      introduction of fluorous-tagged pyrrolidine moieties onto the SWNT surface (1/108
      functional coverage) yields novel FT-CNS (carbon nanostructures) with high
      affinity for fluorinated phases.

PMID- 19847826
TI  - pH-Modulated Watson-Crick duplex-quadruplex equilibria of guanine-rich and
      cytosine-rich DNA sequences 140 base pairs upstream of the c-kit transcription
      initiation site.
AB  - Guanine-rich regions of DNA are sequences capable of forming G-quadruplex
      structures. The formation of a G-quadruplex structure in a region 140 base pairs
      (bp) upstream of the c-kit transcription initiation site was recently proposed
      (Fernando et al., Biochemistry, 2006, 45, 7854). In the present study, the acid
      base equilibria and the thermally induced unfolding of the structures formed by a
      guanine-rich region and by its complementary cytosine-rich strand in c-kit were
      studied by means of circular dichroism and molecular absorption spectroscopies.
      In addition, competition between the Watson-Crick duplex and the isolated
      structures was studied as a function of pH value and temperature. Multivariate
      data analysis methods based on both hard and soft modeling were used to allow
      accurate quantification of the various acid-base species present in the mixtures.
      Results showed that the G-quadruplex and i-motif coexist with the Watson-Crick
      duplex over the pH range from 3.0 to 6.5, approximately, under the experimental
      conditions tested in this study. At pH 7.0, the duplex is practically the only
      species present.

PMID- 19847825
TI  - Hydroxycinnamic acids as DNA-cleaving agents in the presence of Cu(II) ions:
      mechanism, structure-activity relationship, and biological implications.
AB  - The effectiveness of hydroxycinnamic acids (HCAs), that is, caffeic acid (CaA),
      chlorogenic acid (ChA), sinapic acid (SA), ferulic acid (FA), 3-hydroxycinnamic
      acid (3-HCA), and 4-hydroxycinnamic acid (4-HCA), as pBR322 plasmid DNA-cleaving
      agents in the presence of Cu(II) ions was investigated. Compounds bearing o
      hydroxy or 3,5-dimethoxy groups on phenolic rings (CaA, SA, and ChA) were
      remarkably more effective at causing DNA damage than the compounds bearing no
      such groups; furthermore, CaA was the most active among the HCAs examined. The
      involvement of reactive oxygen species (ROS) and Cu(I) ions in the DNA damage was
      affirmed by the inhibition of the DNA breakage by using specific scavengers of
      ROS and a Cu(I) chelator. The interaction between CaA and Cu(II) ions and the
      influence of ethylenediaminetetraacetic acid (EDTA), the solvent, and pH value on
      the interaction were also studied to help elucidate the detailed prooxidant
      mechanism by using UV/Vis spectroscopic analysis. On the basis of these
      observations, it is proposed that it is the CaA phenolate anion, instead of the
      parent molecule, that chelates with the Cu(II) ion as a bidentate ligand, hence
      facilitating the intramolecular electron transfer to form the corresponding CaA
      semiquinone radical intermediate. The latter undergoes a second electron transfer
      with oxygen to form the corresponding o-quinone and a superoxide, which play a
      pivotal role in the DNA damage. The intermediacy of the semiquinone radical was
      supported by isolation of its dimer from the Cu(II)-mediated oxidation products.
      Intriguingly, CaA was also the most cytotoxic compound among the HCAs toward
      human promyelocytic leukemia (HL-60) cell proliferation. Addition of exogenous
      Cu(II) ions resulted in an effect dichotomy on cell viability depending on the
      concentration of CaA; that is, low concentrations of CaA enhanced the cell
      viability and, conversely, high concentrations of CaA almost completely inhibited
      the cell proliferation. On the other hand, when superoxide dismutase was added
      before, the two stimulation effects of exogenous Cu(II) ions were significantly
      ameliorated, thus clearly indicating that the oxidative-stress level regulates
      cell proliferation and death. These findings provide direct evidence for the
      antioxidant/prooxidant mechanism of cancer chemoprevention.

PMID- 19847827
TI  - A periodic mesoporous organosilica-based donor-acceptor system for photocatalytic
      hydrogen evolution.
AB  - A new solid-sate donor-acceptor system based on periodic mesoporous organosilica
      (PMO) has been constructed. Viologen (Vio) was covalently attached to the
      framework of a biphenyl (Bp)-bridged PMO. The diffuse reflectance spectrum showed
      the formation of charge-transfer (CT) complexes of Bp in the framework with Vio
      in the mesochannels. The transient absorption spectra upon excitation of the CT
      complexes displayed two absorption bands due to radical cations of Bp and Vio
      species, which indicated electron transfer from Bp to Vio. The absorption bands
      slowly decayed with a half-decay period of approximately 10 mus but maintained
      the spectral shape, thereby suggesting persistent charge separation followed by
      recombination. To utilize the charge separation for photocatalysis, Vio-Bp-PMO
      was loaded with platinum and its photocatalytic performance was tested. The
      catalyst successfully evolved hydrogen with excitation of the CT complexes in the
      presence of a sacrificial agent. In contrast, reference catalysts without either
      Bp-PMO or Vio gave no or little hydrogen generation, respectively. In addition, a
      homogeneous solution system of Bp molecules, methylviologen, and colloidal
      platinum also evolved no hydrogen, possibly due to a weaker electron-donating
      feature of molecular Bp than that of densely packed Bp in Bp-PMO. These results
      indicated that densely packed Bp and Vio are essential for hydrogen evolution in
      this system and demonstrated the potential of PMO as the basis for donor-acceptor
      systems suitable for photocatalysis.

PMID- 19847828
TI  - Nickel-catalyzed cross-coupling of alkyl zinc halides for the formation of
      C(sp(2))-C(sp(3)) bonds: scope and mechanism.
AB  - Optimal conditions for a general Ni-catalysed Negishi cross-coupling of alkyl
      zinc halides with aryl, heteroaryl and alkenyl halides have been determined.
      These conditions allow the reaction to take place smoothly, with low catalyst
      loading, and in the presence of a wide variety of functional groups to afford
      products in good yields at room temperature. DFT studies on the mechanism support
      the occurrence of a catalytic cycle involving transmetalation of the alkyl zinc
      halide to Ni(I) followed by oxidative addition of the haloarene and C-C reductive
      elimination.

PMID- 19847829
TI  - From byproducts to efficient fluorophores: a route to the synthesis of
      fluorubines.
AB  - The reaction of bis(imidoyl) chlorides of oxalic acid with monoalkyl hydrazines
      leads to substituted Delta(2)-1,2-diazetines, which are versatile building blocks
      for ring-transformation reactions. One remarkable product originating from side
      reactions featured by a strong orange/red fluorescence was confirmed as a novel
      fluorubine derivative. In continuing our studies to substituted oligoazaacenes,
      we developed several synthetic entries to build up novel fluorubine derivatives,
      in which particularly aminobridged bis(quinoxaline)s are the key products for
      cationic hexaazapentacenes. We would like to discuss the possible formation
      pathways of these fluorubine derivatives, which exhibit interesting photophysical
      and chemical properties. The structures of all new derivatives were confirmed by
      common analytical methods (NMR spectroscopy, CV, UV/Vis, mass spectrometry,
      elemental analysis, and X-ray structural analysis) and will be discussed on
      selected examples in more detail.

PMID- 19847830
TI  - Observing second-order nonlinear optical properties by symmetry breaking in
      centrosymmetric furan-containing oligoaryl cyclophandienes.
AB  - Centrosymmetric furan-containing cyclophandienes 3 and 4, synthesized by our
      furan annulation protocol, have been shown to exhibit extraordinarily large
      Stokes shifts and second-order nonlinear optical beta values. The beta values for
      3 and 4 measured at 1.32 mum are 208 and 530x10(-30) esu, respectively. The beta
      values of 3 and 4 are similar to those of respective cyclophenes 1 a and 7 in
      which strong hyperpoarizable interactions between two twisted pi-systems
      (oligoaryl and bridging double bond) might take place. Symmetry breaking due to
      the resonance contribution (cf. 2) and the unique structural features of 3 and 4
      has been used to account for this unusual photophysical behavior.

PMID- 19847831
TI  - Conformationally unambiguous spin labeling for distance measurements.

PMID- 19847832
TI  - Pentacene-based polycyclic aromatic hydrocarbon dyads with cofacial solid-state
      pi-stacking.

PMID- 19847833
TI  - Shape-persistent binuclear cyclometalated platinum(II) luminophores: pushing pi
      mediated excimeric fluid emissions into the NIR region and ion-induced
      perturbations.

PMID- 19847834
TI  - Three-dimensional nanostructured substrates toward efficient capture of
      circulating tumor cells.

PMID- 19847835
TI  - Chemically controlled conductivity: torsion-angle dependence in a single-molecule
      biphenyldithiol junction.

PMID- 19847836
TI  - Super high threshold percolative ferroelectric/ferrimagnetic composite ceramics
      with outstanding permittivity and initial permeability.

PMID- 19847837
TI  - Highly selective oxidation of organosilanes to silanols with hydrogen peroxide
      catalyzed by a lacunary polyoxotungstate.

PMID- 19847838
TI  - Layer-by-layer platform technology for small-molecule delivery.

PMID- 19847839
TI  - Enantioselective one-pot organocatalytic Michael addition/gold-catalyzed tandem
      acetalization/cyclization.

PMID- 19847840
TI  - From branched networks of actin filaments to bundles.
AB  - Cross-linking proteins can mediate the emergence of rigid bundles from a dense
      branched network of actin filaments. To enable their binding, the filaments must
      first bend towards each other. We derive an explicit criterion for the onset of
      bundling, in terms of the initial length of filaments L, their spacing b, and
      cross-linker concentration f, reflecting the balance between bending and binding
      energies. Our model system contains actin, the branching complex Arp2/3 and the
      bundling protein fascin. In the first distinct stage, during which only actin and
      Arp2/3 are active, an entangled aster-like mesh of actin filaments is formed.
      Tens of seconds later, when filaments at the aster periphery are long and barely
      branched, a sharp transition takes place into a star-like structure, marking the
      onset of bundling. Now fascin and actin govern bundle growth; Arp2/3 plays no
      role. Using kinetic Monte Carlo simulations we calculate the temporal evolution
      of b and L, and predict the onset of bundling as a function of f. Our predictions
      are in good qualitative agreement with several new experiments that are reported
      herein and demonstrate how f controls the aster-star transition and bundle
      length. We also present two models for aster growth corresponding to different
      experimental realizations. The first treats filament and bundle association as an
      irreversible sequence of elongation-association steps. The second, applicable for
      low f, treats bundling as a reversible self-assembly process, where the optimal
      bundle size is dictated by the balance between surface and bending energies.
      Finally, we discuss the relevance of our conclusions for the lamellipodium to
      filopodia transition in living cells, noting that bundles are more likely
      nucleated by "tip complex" cross-linkers (e.g. mDia2 or Ena/VASP), whereas fascin
      is mainly involved in bundle maintenance.

PMID- 19847841
TI  - Molecular mechanism of the hydration of Candida antarctica lipase B in the gas
      phase: Water adsorption isotherms and molecular dynamics simulations.
AB  - Hydration is a major determinant of activity and selectivity of enzymes in
      organic solvents or in gas phase. The molecular mechanism of the hydration of
      Candida antarctica lipase B (CALB) and its dependence on the thermodynamic
      activity of water (a(w)) was studied by molecular dynamics simulations and
      compared to experimentally determined water sorption isotherms. Hydration
      occurred in two phases. At low water activity, single water molecules bound to
      specific water binding sites at the protein surface. As the water activity
      increased, water networks gradually developed. The number of protein-bound water
      molecules increased linearly with a(w), until at a(w)=0.5 a spanning water
      network was formed consisting of 311 water molecules, which covered the
      hydrophilic surface of CALB, with the exception of the hydrophobic substrate
      binding site. At higher water activity, the thickness of the hydration shell
      increased up to 10 A close to a(w)=1. Above a limit of 1600 protein-bound water
      molecules the hydration shell becomes unstable and the formation of pure water
      droplets occurs in these oversaturated simulation conditions. While the structure
      and the overall flexibility of CALB was independent of the hydration state, the
      flexibility of individual loops was sensitive to hydration: some loops, such as
      those part of the substrate-binding site, became more flexible, while other parts
      of the protein became more rigid upon hydration. However, the molecular mechanism
      of how flexibility is related to activity and selectivity is still elusive.

PMID- 19847842
TI  - Increased enantioselectivity by engineering bottleneck mutants in an esterase
      from Pseudomonas fluorescens.
AB  - Four hydrophobic and bulky amino acid residues (F126, F144, F159, and I225) were
      identified to form a bottleneck guarding the entrance to the active site of an
      esterase from Pseudomonas fluorescens (PFE I). Hence, a range of nonpolar amino
      acids were introduced into PFE I to broaden the substrate range and to increase
      enantioselectivity while preserving the hydrophobicity of the tunnel. First,
      single variants were created and then the most enantioselective ones were
      combined to find cooperative effects. This resulted in several mutants, which
      showed substantially enhanced enantioselectivity; for instance, in the kinetic
      resolution of 1-phenyl-1-propyl acetate, with which the wild type only showed
      E=1.2, two mutants gave E>46. For 1-phenyl-1-ethyl acetate enantioselectivity
      increased from approximately 50 to >100 for all mutants studied. Furthermore,
      higher conversions could be found at shorter reaction times; this indicates that
      the mutations not only enhanced selectivity, but that also the entrance into the
      active site was indeed facilitated by these mutations. The experimental results
      could be explained by computer modeling.

PMID- 19847843
TI  - Theoretical investigation on the effect of different nitrogen donors on
      intramolecular Se...N interactions.
AB  - The effect of different donor nitrogen atoms on the strength and nature of
      intramolecular Se...N interactions is evaluated for organoselenium compounds
      having N,N-dimethylaminomethyl (dime), oxazoline (oxa) and pyridyl (py)
      substituents. Quantum chemical calculations on three series of compounds [2
      (dime)C(6)H(4)SeX (1 a-g), 2-(oxa)C(6)H(4)SeX (2 a-g), 2-(py)C(6)H(4)SeX (3 a-g);
      X=Cl, Br, OH, CN, SPh, SePh, CH(3)] at the B3LYP/6-31G(d) level show that the
      stability of different conformers depends on the strength of intramolecular
      nonbonded Se...N interactions. Natural bond orbital (NBO), NBO deletion and atoms
      in molecules (AIM) analyses suggest that the nature of the Se...N interaction is
      predominantly covalent and involves nN-->sigma*(Se--X) orbital interaction. In
      the three series of compounds, the strength of the Se...N interaction decreases
      in the order 3>2>1 for a particular X, and it decreases in the order Cl>Br>OH>SPh
      approximately CN approximately SePh>CH(3) for all the three series 1-3. However,
      further analyses suggest that the differences in strength of Se...N interaction
      in 1-3 is predominantly determined by the distance between the Se and N atoms,
      which in turn is an outcome of specific structures of 1, 2 and 3, and the nature
      of the donor nitrogen atoms involved has very little effect on the strength of
      Se...N interaction. It is also observed that Se...N interaction becomes stronger
      in polar solvents such as CHCl(3), as indicated by the shorter r(Se...N) and
      higher E(Se...N) values in CHCl(3) compared to those observed in the gas phase.

PMID- 19847844
TI  - Coupled modulated bilayers: a phenomenological model.
AB  - We propose a model addressing the coupling mechanism between two spatially
      modulated monolayers. We obtain the mean-field phase diagrams of coupled bilayers
      when the two monolayers have the same preferred modulation wavelength. Various
      combinations of the monolayer modulated phases are obtained and their relative
      stability is calculated. Due to the coupling, a spatial modulation in one of the
      monolayers induces a similar periodic structure in the second one. We have also
      performed numerical simulations for the case when the two monolayers have
      different modulation wavelengths. Complex patterns may arise from the frustration
      between the two incommensurate but annealed structures.

PMID- 19847845
TI  - [6,7]-heterocycle-fused 14-hydroxymorphinan derivatives: design, synthesis, and
      opioid receptor activity.
AB  - A series of new 14-hydroxymorphinan analogues with a thiazole or imidazo[2,1
      b]thiazole fragment as the heterocyclic function fused to ring C were designed
      and synthesized. These compounds can be viewed as the result of a direct
      modification at ring C of the 14-hydroxymorphinan scaffold. Among these
      compounds, three were identified as having potent binding affinity (approximately
      1 nM) at both kappa and mu receptors, and acting as agonists at kappa and partial
      agonists or antagonists at mu receptors. In view of the promising results from
      studies on compounds with mixed kappa and mu receptor activities, these new
      compounds warrant further investigation.

PMID- 19847846
TI  - Synthesis, inhibition potency, binding mode, and antiprotozoal activities of
      fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated
      diaryl sulfide scaffolds.
AB  - Trypanothione reductase (TR) is a flavoenzyme unique to trypanosomatid parasites
      and a target for lead discovery programs. Various inhibitor scaffolds have
      emerged in the past, exhibiting moderate affinity for the parasite enzyme. Herein
      we show that the combination of two structural motifs of known TR inhibitors -
      diaryl sulfides and mepacrine - enables the simultaneous addressing of two
      hydrophobic patches in the active site. The binding efficacy of these conjugates
      is enhanced over that of the respective parent inhibitors. They show K(ic) values
      for the parasite enzyme down to 0.9+/-0.1 microm and exhibit high selectivity for
      TR over human glutathione reductase (GR). Despite their considerable molecular
      mass and in some cases permanent positive charges, in vitro studies revealed
      IC(50) values in the low micromolar to sub-micromolar range against Trypanosoma
      brucei rhodesiense and Trypanosoma cruzi, as well as the malaria parasite
      Plasmodium falciparum, which lack trypanothione metabolism. The inhibitors
      exhibit strong fluorescence due to their aminoacridine moiety. This feature
      allows visualization of the drugs in the parasite where high accumulation was
      observed by fluorescence microscopy even after short exposure times.

PMID- 19847849
TI  - Re: Meta-analysis of defunctioning stomas in low anterior resection for rectal
      cancer.

PMID- 19847851
TI  - Re: Non-heart-beating organ donation.

PMID- 19847853
TI  - Re: Measurement of anal cushions in idiopathic faecal incontinence.

PMID- 19847855
TI  - Re: Long-term outcome of endovascular abdominal aortic aneurysm repair.

PMID- 19847857
TI  - Re: Meta-analysis of randomized controlled trials comparing open and laparoscopic
      ventral and incisional hernia repair with mesh.

PMID- 19847859
TI  - Re: Leucocyte depletion of perioperative blood transfusion does not affect long
      term survival and recurrence in patients with gastrointestinal cancer.

PMID- 19847860
TI  - Systematic review and meta-analysis of enteral nutrition formulations in acute
      pancreatitis.
AB  - BACKGROUND: Although the benefits of enteral nutrition in acute pancreatitis are
      well established, the optimal composition of enteral feeding is largely unknown.
      The aim of the study was to compare the tolerance and safety of enteral nutrition
      formulations in patients with acute pancreatitis. METHODS: Electronic databases
      (Scopus, MEDLINE, Cochrane Controlled Clinical Trials Register) and the
      proceedings of major pancreatology conferences were searched. RESULTS: Twenty
      randomized controlled trials, including 1070 patients, met the inclusion
      criteria. None of the following was associated with a significant difference in
      feeding intolerance: the use of (semi)elemental versus polymeric formulation
      (relative risk (RR) 0.62 (95 per cent confidence interval (c.i.) 0.10 to 3.97); P
      = 0.611); supplementation of enteral nutrition with probiotics (RR 0.69 (95 per
      cent c.i. 0.43 to 1.09); P = 0.110); or immunonutrition (RR 1.60 (95 per cent
      c.i. 0.31 to 8.29); P = 0.583). The risk of infectious complications and death
      did not differ significantly in any of the comparisons. CONCLUSION: The use of
      polymeric, compared with (semi)elemental, formulation does not lead to a
      significantly higher risk of feeding intolerance, infectious complications or
      death in patients with acute pancreatitis. Neither the supplementation of enteral
      nutrition with probiotics nor the use of immunonutrition significantly improves
      the clinical outcomes.

PMID- 19847861
TI  - Pathogenesis of primary varicose veins.
AB  - BACKGROUND: Valvular incompetence and reflux are common features of primary
      varicose veins, and have long been thought to be their cause. Recent evidence,
      however, suggests that changes in the vein wall may precede valvular dysfunction.
      METHODS: A literature search was performed using PubMed and Ovid using the
      keywords 'varicose vein wall changes', 'pathogenesis', 'aetiology' and 'valvular
      dysfunction'. Articles discussing the pathophysiology of complications of
      varicose veins, such as ulceration, recurrence, thrombophlebitis and
      lipodermatosclerosis, were excluded. RESULTS AND CONCLUSION: Positive family
      history, age, sex and pregnancy are important risk factors for varicose vein
      formation. Areas of intimal hyperplasia and smooth muscle cell proliferation are
      often noted in varicose veins, although regions of atrophy are also present. The
      total elastin content in varicose as opposed to non-varicose veins is reduced;
      changes in overall collagen content are uncertain. Matrix metalloproteinases
      (MMPs), including MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9, and tissue inhibitor of
      metalloproteinase (TIMP) 1 and TIMP-3 are upregulated in varicose veins.
      Activation of the endothelium stimulates the recruitment of leucocytes and the
      release of growth factors, leading to smooth muscle cell proliferation and
      migration. Dysregulated apoptosis has also been demonstrated in varicose veins.
      An understanding of the pathophysiology of varicose veins is important in the
      identification of potential therapeutic targets and treatment strategies.

PMID- 19847862
TI  - Varicose veins today.

PMID- 19847863
TI  - Medium-term results of ultrasound-guided foam sclerotherapy for small saphenous
      varicose veins.
AB  - BACKGROUND: The results of surgery for small saphenous varicose vein (SSV)
      varicosities may be suboptimal in terms of recurrence and complications. The role
      of minimally invasive alternatives remains incompletely defined. The aim was to
      review the medium-term outcomes of ultrasound-guided foam sclerotherapy (UGFS)
      for SSV. METHODS: Eighty-six patients (92 legs) undergoing UGFS for SSV were
      assessed before, and 1, 6 and 12 months after treatment. Outcome measures were
      occlusion of, and abolition of reflux in, the SSV (technical success), absence of
      visible varicose veins (clinical success) and improvement in disease-specific
      health-related quality of life (HRQL) following treatment (Aberdeen Varicose Vein
      Symptom Severity Score (AVSS)). RESULTS: The technical and clinical success rates
      at 12 months were 91 and 93 per cent respectively; only three patients required a
      second treatment. After treatment of isolated SSV varicosities there was a
      significant improvement in AVSS, from a median of 19.0 (interquartile range 13.4
      26.8) before treatment to 10.2 (4.0-18.3) and 9.7 (3.5-19.1) at 6 and 12 months
      respectively. The only complication was a popliteal vein thrombosis that required
      anticoagulation. CONCLUSION: UGFS was an effective treatment for SSV, with
      abolition of reflux and visible varicose veins, and improvement in HRQL for at
      least 12 months.

PMID- 19847864
TI  - Recovery after ultrasound-guided foam sclerotherapy compared with conventional
      surgery for varicose veins.
AB  - BACKGROUND: The advantages of minimally invasive alternatives such as ultrasound
      guided foam sclerotherapy (UGFS) over conventional surgery for the treatment of
      varicose veins include lower morbidity and faster recovery times. The aim was to
      compare morbidity, analgesia use, and time to return to driving and work
      following UGFS with those reported after conventional surgery for varicose veins.
      METHODS: Patients who had UGFS or surgery for varicose veins were sent a
      questionnaire 4 weeks after treatment. RESULTS: A total of 332 (84.9 per cent) of
      391 patients who had UGFS and 53 (56 per cent) of 94 who had surgery returned a
      questionnaire. The groups were similar in terms of age, sex, and the proportion
      who had treatment of bilateral or recurrent veins. Patients who had surgery were
      more likely to have significant bruising (44 versus 7.2 per cent; P < 0.001) and
      pain (17 versus 5.5 per cent; P = 0.001). After UGFS, 43.2 per cent of patients
      returned to work within 24 h compared with none who had surgery (P < 0.001).
      Patients who had UGFS were more likely to return to driving within 4 days (P =
      0.014). CONCLUSION: UGFS was associated with less pain and analgesia requirement,
      time off work and quicker return to driving.

PMID- 19847865
TI  - Randomized clinical trial of the effect of glucocorticoids on peritoneal
      inflammation and postoperative recovery after colectomy.
AB  - BACKGROUND: Recent data have suggested a relationship between postoperative
      fatigue and the peritoneal cytokine response after surgery. The aim of this study
      was to test the hypothesis that preoperative administration of glucocorticoids
      before surgery would decrease fatigue and enhance recovery, by reducing the
      peritoneal production of cytokines. METHODS: In a double-blind randomized
      controlled study, patients undergoing elective, open colonic resection were
      administered 8 mg dexamethasone or normal saline. Patients were treated within an
      enhanced recovery after surgery programme. Primary outcomes were cytokine levels
      in peritoneal drain fluid and fatigue as measured by the Identity-Consequence
      Fatigue Scale (ICFS). RESULTS: Baseline parameters were similar for 29 patients
      in the dexamethasone group and 31 in the placebo group. Patients who received
      dexamethasone had lower ICFS scores on days 3 and 7. Dexamethasone was associated
      with significantly lower peritoneal fluid interleukin (IL) 6 and IL-13
      concentrations on day 1, and these correlated with changes in the ICFS score.
      There was no significant increase in adverse events in the dexamethasone group.
      CONCLUSION: Preoperative administration of dexamethasone resulted in a
      significant reduction in early postoperative fatigue, associated with an
      attenuated early peritoneal cytokine response. Peritoneal production of cytokines
      may therefore be important in postoperative recovery. REGISTRATION NUMBER:
      ACTRN12607000066482 (http://www.anzctr.org.au/).

PMID- 19847866
TI  - Hospital volume influences the choice of operation for thyroid cancer.
AB  - BACKGROUND: Many authors advocate total or near-total thyroidectomy for thyroid
      carcinoma. This study examined the relationship between hospital volume of
      thyroidectomies and choice of bilateral thyroidectomy for thyroid carcinoma.
      METHODS: Data were extracted from the administrative databases of all hospital
      discharge abstracts in the Rhone-Alpes area of France. The study population
      included inpatient stays from 1999 to 2004 with a diagnosis of thyroid disease
      (benign or malignant) and a procedural code for thyroid surgery. Multivariable
      logistic regression analyses were performed to determine factors associated with
      the extent of surgery (unilateral versus bilateral) for thyroid carcinoma.
      RESULTS: A total of 20 140 thyroidectomies were identified, including 4006
      procedures for cancer. Compared with hospitals performing a high volume of
      procedures for all thyroid diseases (at least 100 annually), the risk of a
      unilateral procedure for thyroid cancer increased by 2.46 (95 per cent confidence
      interval 1.63 to 3.71) in low-volume hospitals (fewer than ten operations per
      year) and by 1.56 (1.27 to 1.92) in medium-volume centres (ten to 99 per year).
      CONCLUSION: There is a significant relationship between hospital volume and the
      decision to perform bilateral surgery for thyroid carcinoma. Thyroid cancer
      surgery should be performed by experienced surgical teams in high-volume centres.

PMID- 19847867
TI  - Circumferential resection margin as a prognostic factor in rectal cancer.
AB  - BACKGROUND: This study examined the prognostic impact of the circumferential
      resection margin (CRM) in patients with rectal cancer treated by total mesorectal
      excision (TME) with or without radiotherapy. METHODS: A national population-based
      rectal cancer registry included 3196 patients with known CRM status between 1993
      and 2004. Some 90.5 per cent of the patients had surgery alone and 9.5 per cent
      had preoperative radiotherapy. Patients who did not have TME, those in whom the
      CRM was not measured, patients with intraoperative bowel or tumour perforation
      and those who received postoperative radiotherapy were excluded. RESULTS: Five
      year local recurrence, distant metastasis and overall survival rates were 23.7,
      43.9 and 44.5 per cent respectively for patients with a CRM of 0-2 mm, compared
      with 8.9, 21.7 and 66.7 per cent respectively for those with wider margins. A CRM
      of 2 mm or less had an impact on the prognosis of T2 and T3 tumours located 6-15
      cm above the anal verge, but not on lower tumours. CRM also had a prognostic
      impact on the three endpoints in patients who received preoperative radiotherapy,
      but with less precision. CONCLUSION: A CRM of 2 mm or less confers a poorer
      prognosis and patients should be considered for neoadjuvant treatment.

PMID- 19847868
TI  - Long-term surveillance with computed tomography after endovascular aneurysm
      repair may not be justified.
AB  - BACKGROUND: There is a common perception that a large number of secondary
      interventions are needed following endovascular aortic aneurysm repair. METHODS:
      Prospective data were collected for a cohort of 417 consecutive elective patients
      undergoing infrarenal aortic endograft repair between April 2000 and May 2008.
      The rate of secondary interventions, associated morbidity and need for
      reintervention following surveillance imaging were analysed. RESULTS: The male :
      female ratio was 11 : 1, median age 76 (range 40-93) years and median aneurysm
      diameter 6.1 (5.3-11) cm. The overall 30-day mortality rate was 1.7 per cent
      (seven of 417). Secondary interventions were performed in 31 patients (7.4 per
      cent), of which six (1.4 per cent) were detected by surveillance. Endoleaks
      requiring reintervention occurred in 12 patients (2.9 per cent; ten type I and
      two type III endoleaks). Limb ischaemia secondary to graft occlusion occurred in
      17 patients (4.1 per cent); extra-anatomical bypass was needed in 15 patients
      (3.6 per cent) and the remaining two had an amputation. Graft explantation
      following late infection was required in two patients (0.5 per cent). CONCLUSION:
      Endoluminal repair of infrarenal aortic aneurysms can be performed with a low
      reintervention rate. The value of prolonged surveillance seems limited and
      current surveillance protocols may require revision.

PMID- 19847869
TI  - Preoperative localization of sentinel lymph nodes using intradermal microbubbles
      and contrast-enhanced ultrasonography in patients with breast cancer.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard procedure for
      axillary staging in early breast cancer. Lymphatic imaging after intraparenchymal
      microbubble injection has been reported in animal models. The aim of this study
      was to identify and localize SLNs before surgery by contrast-enhanced
      ultrasonography after intradermal injection of microbubbles in patients with
      breast cancer. METHODS: Fifty-four consecutive, consenting patients with primary
      breast cancer were recruited. Patients received a periareolar intradermal
      injection of microbubble contrast agent. Breast lymphatics were visualized by
      ultrasonography and followed to identify putative axillary SLNs. A guidewire was
      deployed to localize the SLN. The next day, patients underwent standard tumour
      excision and SLN biopsy. RESULTS: SLNs were identified and guidewires inserted in
      48 patients. In these patients operative findings confirmed that the wired lymph
      nodes were SLNs. The sensitivity of SLN detection, compared with radioisotope and
      blue dye, was 89 per cent. Five patients were found to have metastases in SLNs.
      In these patients the SLNs were identified correctly and localized before surgery
      with guidewires. CONCLUSION: SLNs may be identified and localized before surgery
      using contrast-enhanced ultrasonography after injection of microbubbles.

PMID- 19847870
TI  - Haemoglobin A1c as a predictor of postoperative hyperglycaemia and complications
      after major colorectal surgery.
AB  - BACKGROUND: Hyperglycaemia following major surgery increases morbidity, but may
      be improved by use of enhanced-recovery protocols. It is not known whether
      preoperative haemoglobin (Hb) A1c could predict hyperglycaemia and/or adverse
      outcome after colorectal surgery. METHODS: Some 120 patients without known
      diabetes underwent major colorectal surgery within an enhanced-recovery protocol.
      HbA1c was measured at admission and 4 weeks after surgery. All patients received
      an oral diet beginning 4 h after operation. Plasma glucose was monitored five
      times daily. Patients were stratified according to preoperative levels of HbA1c
      (within normal range of 4.5-6.0 per cent, or higher). RESULTS: Thirty-one
      patients (25.8 per cent) had a preoperative HbA1c level over 6.0 per cent. These
      had higher mean(s.d.) postoperative glucose (9.3(1.5) versus 8.0(1.5) mmol/l; P <
      0.001) and C-reactive protein (137(65) versus 101(52) mg/l; P = 0.008) levels
      than patients with a normal HbA1c level. Postoperative complications were more
      common in patients with a high HbA1c level (odds ratio 2.9 (95 per cent
      confidence interval 1.1 to 7.9)). CONCLUSION: Postoperative hyperglycaemia is
      common among patients with no history of diabetes, even within an enhanced
      recovery protocol. Preoperative measurement of HbA1c may identify patients at
      higher risk of poor glycaemic control and postoperative complications.

PMID- 19847871
TI  - Long-term weight change after oesophageal cancer surgery.
AB  - BACKGROUND: Malnutrition is common after oesophageal cancer surgery. This study
      investigated weight changes and the risk of malnutrition among long-term
      survivors. METHODS: A nationwide cohort study was conducted in Sweden in 2001
      2004, with follow-up to 2008. Weight was assessed before oesophagectomy, after 6
      months and at 3 years. Logistic regression was performed with adjustment for
      confounders. Odds ratios (ORs) for postoperative weight loss of at least 15 per
      cent were estimated. RESULTS: Some 203 patients survived at least 3 years after
      oesophagectomy. Continuous weight loss occurred for up to 3 years. Women and men
      had a similar risk of malnutrition after 3 years (OR 0.85 (95 per cent confidence
      interval 0.24 to 2.98)). In overweight patients (preoperative body mass index at
      least 25 kg/m(2)) the risk of malnutrition was increased almost fivefold at 6
      months (OR 4.90 (2.27 to 10.59)) and 3 years (OR 4.60 (1.80 to 11.78)). There was
      no difference in weight loss at 6 months between survivors and those who died
      between 6 months and 3 years after surgery (OR 1.11 (0.64 to 1.94)). CONCLUSION:
      Weight loss can be long lasting after oesophagectomy; overweight patients are at
      particularly increased risk of malnutrition.

PMID- 19847872
TI  - Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal
      adhesion in an experimental model.
AB  - BACKGROUND: Postoperative intra-abdominal adhesion is associated with high
      morbidity and mortality. Smad7, a protein that occupies a strategic position in
      fibrogenesis, inhibits the transforming growth factor (TGF) beta/Smad signalling
      pathway. In this study the therapeutic potential of exogenous Smad7 in preventing
      fibrogenesis in postoperative intra-abdominal adhesion was investigated. METHODS:
      Intra-abdominal adhesion was induced in a rodent model by peritoneal abrasion.
      Smad7 was delivered into the peritoneal cavity by a non-viral ultrasound
      microbubble-mediated naked gene transfection system. The effect of Smad7
      transgene on adhesion formation was studied by measuring changes in TGF-beta,
      fibrogenic factors, alpha-SMA and Smad2/3 activation in the anterior abdominal
      wall. RESULTS: Four weeks after surgical abrasion, all rats developed significant
      peritoneal adhesion with enhanced TGF-beta expression, increased levels of
      extracellular matrix components and activated myofibroblasts, accompanied by
      decreased Smad7 expression and increased Smad2/3 activation. In rats treated with
      the Smad7 transgene, the incidence and severity of peritoneal adhesion were
      significantly reduced, with biochemical downregulation of fibrogenic factors and
      inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance
      imaging revealed a significant reduction in adhesion areas from day 14 onwards.
      CONCLUSION: Ultrasound-microbubble-mediated gene transfection provides timely
      targeted gene delivery for the treatment of postoperative peritoneal adhesions.

PMID- 19847873
TI  - Sentinel lymph node biopsy in breast cancer guided by indocyanine green
      fluorescence.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy with radioisotope and blue dye has
      been used successfully for axillary staging in breast cancer. This study
      evaluated the feasibility of fluorescence detection of SLNs with indocyanine
      green (ICG) for lymphatic mapping and SLN biopsy. METHODS: Thirty women with
      breast cancer had a periareolar injection of ICG for fluorescence detection of
      SLN using a near-infrared camera. Twenty also received (99m)Tc-labelled sulphur
      radiocolloid for SLN scintigraphy. All patients underwent axillary lymph node
      dissection. Detection rate and sensitivity of both methods were the study
      endpoints. RESULTS: Visualization of lymphatic vessels by fluorescence detection
      depended on the dose of ICG. ICG imaging identified SLNs in 29 of 30 women
      (detection rate 97 per cent). Nineteen of 21 patients had metastatic SLN
      involvement (sensitivity 90 per cent) with false-negative results in two. Among
      the 20 patients who had both methods, ICG fluorescence and radiocolloid
      identified SLNs in 20 and 17 patients respectively. Metastatic lymph nodes were
      diagnosed in 12 and ten of 13 patients (sensitivity 92 and 77 per cent). False
      negative rates were 8 and 23 per cent respectively. CONCLUSION: ICG fluorescence
      allowed transcutaneous imaging of lymphatic vessels and SLN detection, thus
      combining the advantages of radioisotope and blue dye methods.

PMID- 19847874
TI  - Genetic and environmental influences on the risk of acute appendicitis in twins.
AB  - BACKGROUND: Acute appendicitis is common but the aetiology is unclear. This study
      examined the heritability of acute appendicitis. METHODS: The study included twin
      pairs with known zygosity born between 1959 and 1985. Individuals with acute
      appendicitis were found by record linkage with the Swedish Inpatient Register.
      Comparing monodizygotic and dizygotic twins, the similarity and relative
      proportions of phenotypic variance resulting from genetic and environmental
      factors were analysed. Risks of acute appendicitis explained by heritability and
      environmental effects were estimated. RESULTS: Some 3441 monozygotic and 2429
      dizygotic twins were identified. Almost no genetic effects were found in males (8
      (95 per cent confidence interval 0 to 50) per cent), but shared (31 (0 to 49) per
      cent) and non-shared (61 (47 to 74) per cent) environmental factors accounted for
      this risk. In females, the heritability was estimated as 20 (0 to 36) per cent
      and the remaining variation was due to non-shared environmental factors (80 (64
      to 98) per cent). For the sexes combined, genetic effects accounted for 30 (5 to
      40) per cent and non-shared environmental effects for 70 (60 to 81) per cent of
      the risk. CONCLUSION: Acute appendicitis has a complex aetiology with sex
      differences in heritability and environmental factors.

PMID- 19847876
TI  - Damage control in burn surgery.

PMID- 19847875
TI  - Stage-for-stage comparison of definitive chemoradiotherapy, surgery alone and
      neoadjuvant chemotherapy for oesophageal carcinoma.
AB  - BACKGROUND: Definitive chemoradiotherapy (dCRT) has been proposed as an
      alternative therapy for selected patients with oesophageal cancer. The aim of
      this study was to determine the outcomes of dCRT, surgery alone, and neoadjuvant
      chemotherapy followed by surgery (CS) in patients with oesophageal cancer.
      METHODS: Consecutive patients diagnosed with oesophageal cancer and managed by a
      multidisciplinary team were staged by computed tomography and endoluminal
      ultrasonography. Those deemed unsuitable for surgery on the grounds of
      performance status, bulky local disease or personal choice received dCRT. The
      primary outcome measure was overall survival measured from date of diagnosis.
      RESULTS: Of 417 patients, 173 received dCRT, 126 underwent surgery alone and 118
      received CS. The incidence of grade III/IV toxicity after dCRT and CS was 39.3
      and 60.2 per cent respectively. Operative morbidity rates were 42.9 and 44.4 per
      cent after surgery alone and CS respectively. Thirty-day mortality rates were
      zero, 7.9 and 0.8 per cent after dCRT, surgery alone and CS respectively. Overall
      2-year survival rates were 44.3, 56.2 and 42.4 per cent (P = 0.422). CONCLUSION:
      These findings support the need for a randomized trial of dCRT versus CS for
      resectable oesophageal cancer.

PMID- 19847877
TI  - Abdominosacral resection for locally advanced and recurrent rectal cancer.
AB  - BACKGROUND: The results of resection of locally advanced and recurrent rectal
      cancers, including sacral resection, were analysed critically. METHODS: Between
      1987 and 2007, 353 patients with locally advanced or recurrent rectal cancer, all
      treated in a tertiary referral centre, were identified from a prospective
      database. Twenty-five patients (eight primary and 17 recurrent tumours) underwent
      en bloc sacral resection. RESULTS: A mid-sacral resection was carried out in 12
      patients (level S3) and a low sacral resection in 13 (level S4/S5). Nineteen
      patients had an R0, four an R1 and two an R2 resection. There was no
      postoperative mortality. Median follow-up was 32 months. Incomplete resection had
      an independent negative influence on local control (5-year local recurrence rate
      42 versus 0 per cent in those with and without incomplete resection; P < 0.001).
      The 5-year overall survival rate was 30 per cent. Five patients with recurrent
      tumour had pathological invasion into the sacral bone and none survived beyond 1
      year. CONCLUSION: Abdominosacral resection can be performed in patients with
      locally advanced and recurrent rectal cancer. Patients who cannot undergo a
      complete resection or have clear evidence of cortical invasion have a poor
      prognosis.

PMID- 19847878
TI  - Incidence of and potential risk factors for gallstone disease in a general
      population sample.
AB  - BACKGROUND: Several epidemiological studies have been published, but there are
      few reports on relations between gallstone incidence, symptomatology and risk
      factors. METHODS: Of 621 randomly selected individuals aged 35-85 years in a
      general population who had been screened previously with ultrasonography and
      found to have no gallbladder stones, 503 (81.0 per cent) were re-examined after a
      minimum interval of 5 years. At baseline and re-examination, heredity for
      gallstone disease was explored and body mass index, digestive symptoms including
      abdominal pain, quality of life, alcohol and smoking habits, use of non-steroidal
      anti-inflammatory drugs and oestrogen, parity and blood lipid levels were
      recorded. RESULTS: Forty-two (8.3 per cent) of the 503 subjects developed stones.
      Subjects were followed for a total of 3025.8 person-years, yielding an incidence
      for newly developed gallstones of 1.39 per 100 person-years. A positive
      association for gallstone development was found only for length of follow-up and
      plasma low-density lipoprotein-cholesterol levels at baseline. Weekly alcohol
      consumption was inversely related to gallstone development. CONCLUSION: The
      incidence of gallstones in this population was 1.39 per 100 person-years.
      Gallstone development was related to length of follow-up and LDL-cholesterol
      levels, and inversely related to alcohol consumption.

PMID- 19847879
TI  - Cost-effectiveness and quality-of-life analysis of physician-staffed helicopter
      emergency medical services.
AB  - BACKGROUND: The long-term health outcomes and costs of helicopter emergency
      medical services (HEMS) assistance remain uncertain. The aim of this study was to
      investigate the cost-effectiveness of HEMS assistance compared with emergency
      medical services (EMS). METHODS: A prospective cohort study was performed at a
      level I trauma centre. Quality-of-life measurements were obtained at 2 years
      after trauma, using the EuroQol-Five Dimensions (EQ-5D) as generic measure to
      determine health status. Health outcomes and costs were combined into costs per
      quality-adjusted life year (QALY). RESULTS: The study population receiving HEMS
      assistance was more severely injured than that receiving EMS assistance only.
      Over the 4-year study interval, HEMS assistance saved a total of 29 additional
      lives. No statistically significant differences in quality of life were found
      between assistance with HEMS or with EMS. Two years after trauma the mean EQ-5D
      utility score was 0.70 versus 0.71 respectively. The incremental cost
      effectiveness ratio for HEMS versus EMS was 28,327 Euro per QALY. The sensitivity
      analysis showed a cost-effectiveness ratio between 16,000 and 62,000 Euro.
      CONCLUSION: In the Netherlands, the costs of HEMS assistance per QALY remain
      below the acceptance threshold. HEMS should therefore be considered as cost
      effective.

PMID- 19847880
TI  - Quality of life after surgical reduction for severe primary lymphoedema of the
      limbs and genitalia.
AB  - BACKGROUND: The aim was to assess the quality of life (QoL) of patients who had
      surgery for primary lymphoedema. METHODS: A QoL questionnaire was administered to
      patients who had surgery between 1981 and 2003 (retrospective group) and between
      2003 and 2006 (prospective group). RESULTS: The response rate was 70.3 per cent
      (109 of 155 patients): 88 patients had limb reduction (78, retrospective; ten,
      prospective) and 21 had genital reduction (13, retrospective; eight,
      prospective). Forty-nine patients (63 per cent) who had limb reduction studied
      retrospectively reported satisfaction with the procedure and most of these would
      opt for surgery again. In the prospectively studied group, nine of ten patients
      reported improved limbs, and seven would opt for surgery again. Nineteen of 21
      patients who had genital reduction would choose to have surgery again if needed
      (11 of the retrospectively assessed group and all of the prospective group).
      Patients' perception that surgery was worthwhile was greater in both of the
      prospectively assessed groups (P = 0.013). CONCLUSION: Surgery for severe
      lymphoedema improved QoL at early assessment. This, however, may not be
      sustained. Genital reduction appeared to provide greater benefit than limb
      reduction.

PMID- 19847881
TI  - Measuring change in professionalism attitudes during the gross anatomy course.
AB  - By design or default, anatomy educators are often responsible for introducing
      students to medical professionalism. Although much has been said about the role
      of anatomical education, there are no published reports suggesting how to measure
      change. This study investigated what professionalism attitudes, if any, change
      during a gross anatomy course. Additionally, the influence of four dichotomous
      variables related to student identity and preparation for medical school were
      analyzed for their effect on professionalism attitudes. A cross-sectional time
      one (T1; beginning of the course), time-two (T2; end of the course) study using
      the Penn State College of Medicine Survey of Professionalism was conducted. A
      multivariate analysis of variance identified the main effects and interaction
      effects of categorical variables. A Mann Whitney U test verified significant
      differences. This study found a reprioritization of professionalism attitudes in
      favor of altruism (P = 0.04 with a Cohen's d = 0.26) at T2. Female students (P =
      0.03, Cohen's d = 0.38) and students from a science background (P = 0.04, Cohen's
      d = 0.36) changed the most in favor of altruism. Interestingly, though several
      factors correlated with dissimilarities in professionalism values at T1, gender
      was the only factor to show a significant difference in professionalism attitudes
      at T2. This cohort of students reported a statistically significant increase in
      altruism and no significant decreases in other professionalism attitudes
      concurrent with the gross anatomy course.

PMID- 19847882
TI  - A case of luteinizing thecoma with sclerosing peritonitis: revisiting a link with
      anti-epileptic drugs.
AB  - Luteinizing thecoma with sclerosing peritonitis (LTSP) is a rare ovarian tumor of
      unclear etiology and pathogenesis. The diagnostic entity was proposed in 1994,
      but a number of earlier reports described possible cases, and some suggested an
      association with anti-epileptic drugs (AEDs). In presenting a new case we review
      the literature of previous cases to evaluate the possibility of such a link. When
      cases in reproductively immature patients are considered, evidence for an
      association between LTSP and AEDs is strongly suggested despite the rarity of the
      condition.

PMID- 19847883
TI  - Evaluation of a dry format reagent alternative for CD4 T-cell enumeration for the
      FACSCount system: a report on a Moroccan-Canadian study.
AB  - BACKGROUND: Efforts to improve alternative CD4 T-cell counting methods are
      critical to accelerate the implementation of HIV antiretroviral therapy in
      resources limited regions. Substituting liquid format reagents to eliminate cold
      chain transportation and refrigerated storage with dry format reagents
      contributes to higher efficiency supply management solution especially for
      laboratories at remote locations. ReaMetrix has developed dry format reagent kits
      compatible with the FACSCount system, a dedicated flow cytometer for T-cell
      subset enumeration widely used in resource limited settings. A dual site
      collaborative study was designed to compare T-cell subsets using both the new dry
      format ReaMetrix reagent and the original BD Biosciences liquid reagents. METHOD:
      A total of 167 HIV positive samples prepared with Rea T Count (ReaMetrix) and
      FACSCount (BD Biosciences) reagents were analyzed using FACSCount Systems. To
      compare both methods, Bland-Altman, Pollock, Scott % similarity and correlation
      coefficient statistical analysis was applied. Immuno-Trol served as an assay
      processing control and quality indicator of interlaboratory and intralaboratory
      variation. RESULTS: The mean bias and limits of agreement for CD4 T-cell
      measurements between Rea T Count and FACSCount reagents were -16 cells/microl (
      4.6%) and -74 to +43, respectively. The correlation obtained was 0.988 with a
      similarity of 97.9%. Between laboratory variation data was very good with %CV
      below 10%. CONCLUSION: The introduction of dry reagents permits the elimination
      of cold-chain transportation and the on-site refrigerated storage without
      compromise to assay quality. The substitution of dry reagents facilitates easier
      supply management practice that will assure wider access to quality HIV
      treatment.

PMID- 19847884
TI  - Central nervous system relapse of acute promyelocytic leukemia.

PMID- 19847885
TI  - Vector fragmentation: characterizing vector integrity in transfected clones by
      Southern blotting.
AB  - The Chinese Hamster Ovary production cell line development process using
      methotrexate (MTX) amplification is well studied and commonly used for
      biopharmaceutical processes. However, successful MTX amplification varies from
      clone to clone and suggested reasons include vector fragmentation during the
      transfection process and genomic rearrangement of the Chinese Hamster Ovary
      chromosomes. Here, we elucidated the vector integration patterns of 40
      transfected single-cell clones by Southern blotting and showed that vector
      fragmentation occurs at a significant level in our experiment. This concurs with
      MTX amplification studies implying that single-cell cloning is necessary to
      ensure a successful amplification process. Truncations at the ends of the
      integrated vectors were also observed, whereas gross DNA insertions were not
      detected in our data. This suggests that end deletions are common, whereas
      insertion events are rare in animal cells.

PMID- 19847886
TI  - Growth inhibition of dinoflagellate algae in shake flasks: not due to shear this
      time!
AB  - Large scale algae cultures present interesting challenges in that they exhibit
      characteristics of typical bacterial and animal cell cultures. One current
      commercial food additive, docosahexaenoic acid (DHA), is produced using the
      dinoflagellate algae, Crypthecodinium cohnii. Like animal cell culture, the
      perceived sensitivity of algae culture to hydrodynamic forces has potentially
      limited the agitation and aeration applied to these systems. However, the high
      density cultivation of C. cohnii required for an economically feasible process
      inevitably results in high oxygen demand. In this study, we demonstrated what
      first appeared to be a problem with shear sensitivity in shake flasks is most
      probably a mass transfer limitation. We subsequently demonstrated the limit of
      chronic and rapid energy dissipation rate, EDR, that C. cohnii cells can
      experience. This limit was determined using a microfluidic device connected in a
      recirculation loop to a stirred tank bioreactor, which has been previously used
      to repeatedly expose animal cells to high levels of EDR. Inhibition of cell
      growth was observed when C. cohnii cells were subjected to an EDR of 5.9 x 10(6)
      W/m(3) with an average frequency of 0.2/min or more. This level of EDR is
      sufficiently high that C. cohnii can withstand typically encountered hydrodynamic
      forces in bioprocesses. This result suggests that at least one dinoflagellate
      algae, C. cohnii, is quite robust with respect to hydrodynamic forces and the
      scale-up of process using this type of algae should be more concerned with
      providing sufficient gas transfer given the relatively high oxygen demand.

PMID- 19847887
TI  - Gossypium arboreum GHSP26 enhances drought tolerance in Gossypium hirsutum.
AB  - Heat-shock proteins (HSP) are molecular chaperones for protein molecules. These
      proteins play an important role in protein-protein interactions such as, folding
      and assisting in the establishment of proper protein conformation and prevention
      of unwanted protein aggregation. A small HSP gene GHSP26 present in Gossypium
      arboreum responds to dehydration. In the present study, an attempt was made to
      overcome the problem of drought stress in cotton. A cDNA of GHSP26 was isolated
      from G. arboreum, cloned in plant expression vector, pCAMBIA-1301 driven by the
      cauliflower mosaic virus 35S promoter and introduced into Gossypium hirsutum. The
      integration and expression studies of putative transgenic plants were performed
      through GUS assay; PCR from genomic DNA, and quantitative real-time PCR analysis.
      Transgenic cotton plants showed an enhanced drought tolerance, suggesting that
      GHSP26 may play a role in plant responsiveness to drought.

PMID- 19847888
TI  - Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13
      without affecting expressions of types I and III collagen in tendon cells.
AB  - Nonsteroidal antiinflammatory drugs are widely used to treat sports-related
      tendon injuries or tendinopathy. This study was designed to investigate the
      effect of ibuprofen on expressions of types I and III collagen, as well as
      collagen-degrading enzymes including matrix metalloproteinase (MMP)-1, -2, -8, 
      9, and -13. Rat Achilles tendon cells were treated with ibuprofen and then
      underwent MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]
      assay. Reverse transcription-polymerase chain reaction was used to evaluate mRNA
      expressions of types I and III collagen, MMP-1, -2, -8, -9, and -13. Protein
      expressions of types I and III collagen, MMP-1, -8, and -13 were determined by
      Western blot analysis. Gelatin zymography was used to evaluate the enzymatic
      activities of MMP-2 and MMP-9. The results revealed that ibuprofen upregulated
      expressions of MMP-1, -8, -9, and -13, both at mRNA and protein levels. There was
      no effect of ibuprofen on mRNA and protein expressions of types I and III
      collagen. Gelatin zymography revealed that the enzymatic activity of MMP-9 was
      upregulated after ibuprofen treatment. In conclusion, ibuprofen upregulates the
      expressions of collagenases including MMP-1, -8, -9, and -13 without affecting
      the expressions of types I and III collagen. These findings suggest a molecular
      mechanism potentially accounting for the inhibition of tendon healing by
      ibuprofen.

PMID- 19847889
TI  - SUZ12 is a candidate target of the non-canonical WNT pathway in the progression
      of chronic myeloid leukemia.
AB  - Polycomb proteins form multiprotein complexes that repress target genes by
      chromatin remodeling. In this work, we report that the SUZ12 polycomb gene is
      over-expressed in bone marrow samples of patients at the blastic phase of chronic
      myeloid leukemia. We also found a direct interaction between polycomb group genes
      and the WNT signaling pathway in chronic myeloid leukemia transformation.
      Electrophoretic mobility shift assay (EMSA), Chromatin immunoprecipitation assay
      (ChIP), and mass spectrometry assays identified noncanonical WNT pathway members,
      such as WNT5A and WNT11, bound to the SUZ12 promoter. Immunohistochemistry and
      immunofluorescence with WNT5A and WNT11 antibodies confirmed nuclear
      localization. Knockdown of WNTs 1, 5A, and 11 with RNAi approaches showed that
      WNT members are capable of activating SUZ12 transcription with varying promoter
      affinities. Finally, we suggest that SUZ12 is blocking cellular differentiation,
      as SUZ12 knockdown release differentiation programs in chronic myeloid blastic
      phase (CML-BP) transformed cell line.

PMID- 19847890
TI  - Genome-wide scan identifies a copy number variable region at 3q26 that regulates
      PPM1L in APC mutation-negative familial colorectal cancer patients.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited form of
      colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli
      (APC) gene. However, APC mutations are not detected in 10-50% of FAP patients. We
      searched for a new cancer gene by performing genome-wide genotyping on members of
      an APC mutation-negative FAP variant family and ethnicity-matched healthy
      controls. No common copy number change was found in all affected members using
      the unaffected members and healthy controls as baseline. A 111 kb copy number
      variable (CNV) region at 3q26.1 was shown to have copy number loss in all eight
      polyps compared to matched lymphocytes of two affected members. A common region
      of loss in all polyps, which are precursors to CRC, is likely to harbor disease
      causing gene in accordance to Knudsen's "two-hit" hypothesis. There is, however,
      no gene within the deleted region. A 2-Mb scan of the genomic region encompassing
      the deleted region identified PPM1L, coding for a novel serine-threonine
      phosphatase in the TGF-beta and BMP signaling pathways. Real-time PCR analyses
      indicate that the 3'UTR of PPM1L transcript was down-regulated more than two
      folds in all six polyps and tumors compared to matched mucosa of the affected
      member. This down-regulation was not observed in APC mutation-positive FAP
      patients. Our results suggest that the CNV region at 3q26 harbors an element that
      regulates the expression of an upstream candidate tumor suppressor, PPM1L, thus
      providing a novel mechanism for colorectal tumorigenesis in APC mutation-negative
      familial CRC patients.

PMID- 19847891
TI  - Hereditary gastrointestinal stromal tumors sharing the KIT Exon 17 germline
      mutation p.Asp820Tyr develop through different cytogenetic progression pathways.
AB  - Hereditary gastrointestinal stromal tumor (GIST) syndrome is a rare autosomal
      dominant genetic disorder originated by germline mutations in the KIT or PDGFRA
      genes. We report the third family with hereditary predisposition to GIST due to
      the KIT Exon 17 germline mutation p.Asp820Tyr and characterize the cytogenetic
      progression pathways followed by different GIST sharing the same primary genetic
      event, using a combination of chromosome banding, comparative genomic
      hybridization (CGH), and fluorescence in situ hybridization (FISH) analyses. The
      missense mutation p.Asp820Tyr was detected in the proband's rectal and gastric
      GIST, as well as in his aunt's GIST epiplon metastasis. The mutation p.Asp820Tyr
      was subsequently also found in the proband's peripheral blood DNA, as well as in
      that of 4 of 10 relatives thus far analyzed. CGH analysis revealed loss of 14q
      and 15q in the proband's gastric lesion, whereas FISH analysis of the proband's
      rectal GIST did not detect loss of 14q and 15q, but instead loss of 4q and 22q
      and gain of 20q, indicating that the two tumors were independent GIST. Chromosome
      banding and CGH analyses of the aunt's GIST epiplon metastasis revealed multiple
      cytogenetic alterations, including 1p loss, but none in common with the two
      proband's GIST. We conclude that, although the patients share the same KIT Exon
      17 germline mutation, the multiple GIST analyzed followed different pathogenetic
      progression pathways, each of which did not significantly differ from what has
      been described in sporadic GIST.

PMID- 19847894
TI  - Modeling Parkinson's disease.

PMID- 19847896
TI  - Professional exposure to pesticides and Parkinson disease.
AB  - OBJECTIVE: We studied the relation between Parkinson disease (PD) and
      professional exposure to pesticides in a community-based case-control study
      conducted in a population characterized by a high prevalence of exposure. Our
      objective was to investigate the role of specific pesticide families and to
      perform dose-effect analyses. METHODS: PD cases (n = 224) from the Mutualite
      Sociale Agricole (France) were matched to 557 controls free of PD affiliated with
      the same health insurance. Pesticide exposure was assessed using a 2-phase
      procedure, including a case-by-case expert evaluation. Analyses of the relation
      between PD and professional exposure to pesticides were first performed overall
      and by broad category (insecticides, fungicides, herbicides). Analyses of 29
      pesticide families defined based on a chemical classification were restricted to
      men. Multiple imputation was used to impute missing values of pesticide families.
      Data were analyzed using conditional logistic regression, both using a complete
      case and an imputed dataset. RESULTS: We found a positive association between PD
      and overall professional pesticide use (odds ratio [OR] = 1.8, 95% confidence
      interval [CI] = 1.1-3.1), with a dose-effect relation for the number of years of
      use (p = 0.01). In men, insecticides were associated with PD (OR = 2.2, 95% CI =
      1.1-4.3), in particular organochlorine insecticides (OR = 2.4, 95% CI = 1.2-5.0).
      These associations were stronger in men with older onset PD than in those with
      younger onset PD, and were characterized by a dose-effect relation in the former
      group. INTERPRETATION: Our results support an association between PD and
      professional pesticide exposure, and show that some pesticides (ie,
      organochlorine insecticides) may be more particularly involved.

PMID- 19847895
TI  - Ventricular dilation: association with gait and cognition.
AB  - OBJECTIVE: Normal pressure hydrocephalus is characterized by gait impairment,
      cognitive impairment, and urinary incontinence, and is associated with
      disproportionate ventricular dilation. Here we report the distribution of
      ventricular volume relative to sulcal cerebrospinal fluid (CSF) volume, and the
      association of increasing ventricular volume relative to sulcal CSF volume with a
      cluster of gait impairment, cognitive impairment, and urinary incontinence in a
      stroke-free cohort of elderly persons from the general population. METHODS: Data
      are based on 858 persons (35.4% men; age range, 66-92 years) who participated in
      the Age, Gene/Environment Susceptibility-Reykjavik Study. Gait was evaluated with
      an assessment of gait speed. Composite scores representing speed of processing,
      memory, and executive function were constructed from a neuropsychological
      battery. Bladder function was assessed with a questionnaire. Magnetic resonance
      brain imaging was followed by semiautomated segmentation of intracranial CSF
      volume. White matter hyperintensity (WMH) volume was assessed with a
      semiquantitative scale. For the analysis of ventricular dilation relative to the
      sulcal spaces, ventricular volume was divided by sulcal CSF volume (VV/SV).
      RESULTS: Disproportion between ventricular and sulcal CSF volume, defined as the
      highest quartile of the VV/SV z score, was associated with gait impairment (odds
      ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3) and cognitive impairment
      (OR, 1.8; 95% CI, 1.1-3.0). We did not find an association between the VV/SV z
      score and bladder dysfunction. INTERPRETATION: The prevalence and severity of
      gait impairment and cognitive impairment increases with ventricular dilation in
      persons without stroke from the general population, independent of WMH volume.

PMID- 19847897
TI  - Cerebrospinal fluid of brain trauma patients inhibits in vitro neuronal network
      function via NMDA receptors.
AB  - Neurological diseases frequently induce pathological changes of cerebrospinal
      fluid (CSF) that might secondarily influence brain activity, as the CSF-brain
      barrier is partially permeable. However, functional effects of CSF on neuronal
      network activity have not been specified to date. Here, we report that CSF
      specimens from patients with reduced Glasgow Coma Scale values caused by severe
      traumatic brain injury suppress synchronous activity of in vitro-generated
      neuronal networks in comparison with controls. We present evidence that
      underlying mechanisms include increased N-methyl-D-aspartate receptor activity
      mediated by a CSF fraction containing elevated amino acid concentrations. These
      proof-of-principle data suggest that determining effects of CSF specimens on
      neuronal network activity might be of diagnostic value.

PMID- 19847898
TI  - Periodontitis and incidence of cerebrovascular disease in men.
AB  - OBJECTIVE: To identify associations between periodontitis and incidence of
      cerebrovascular disease. METHODS: We analyzed data of 1,137 dentate men in the
      Veterans Affairs Normative Aging and Dental Longitudinal Study who were followed
      with triennial medical/dental exams for up to 34 years (mean, 24 years). We
      evaluated incidence of cerebrovascular events consistent with stroke or transient
      ischemic attack in relation to mean radiographic alveolar bone loss (a measure of
      periodontitis history) and cumulative periodontal probing depth (a measure of
      current periodontal inflammation). Cox proportional hazards models were fit
      controlling for age, baseline socioeconomic status, and time-varying effects of
      established cardiovascular risk factors. RESULTS: Eighty incident cases of
      cerebrovascular disease occurred from 27,506 person-years. Periodontal bone loss
      was significantly associated with an increased hazard rate (HR) of
      cerebrovascular disease (HR, 3.52; 95% confidence interval [CI], 1.59-7.81
      comparing highest to lowest bone loss category; p for trend, <0.001). There was a
      stronger effect among men aged <65 years (HR, 5.81; 95% CI, 1.63-20.7) as
      compared with men aged > or =65 years (HR, 2.39; 95% CI, 0.91-6.25). Periodontal
      probing depth was not associated with a significantly increased rate of
      cerebrovascular disease in the combined or age-stratified analyses.
      INTERPRETATION: These results support an association between history of
      periodontitis-but not current periodontal inflammation-and incidence of
      cerebrovascular disease in men, independent of established cardiovascular risk
      factors, particularly among men aged <65 years.

PMID- 19847899
TI  - Real-life impact of early interferon beta therapy in relapsing multiple
      sclerosis.
AB  - OBJECTIVE: Recent findings support greater efficacy of early vs. delayed
      interferon beta (IFNbeta) treatment in patients with a first clinical event
      suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of
      early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess
      the optimal time to initiate IFNbeta treatment with regard to the greatest
      benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated
      RRMS patients was prospectively followed for up to 7 years in 15 Italian MS
      Centers. A Cox proportional hazards regression model adjusted for propensity
      score (PS) quintiles was used to assess differences between groups of patients
      with early vs. delayed IFNbeta treatment on risk of reaching a 1-point
      progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS
      4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were
      calculated according to different times of treatment initiation (within 1 year up
      to within 5 years from disease onset). A sensitivity analysis was performed to
      assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for
      the three PS quintiles-adjusted models were obtained by a cutoff of treatment
      initiation within 1 year from disease onset. Early treatment significantly
      reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95%
      CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36
      0.90; p = 0.015). Sensitivity analysis showed the bound of significance for
      unmeasured confounders. INTERPRETATION: Greater benefits on disability
      progression may be obtained by an early IFNbeta treatment in RRMS.

PMID- 19847900
TI  - CCL21 overexpressed on lymphatic vessels drives thymic hyperplasia in myasthenia.
AB  - OBJECTIVE: Myasthenia gravis (MG), a neuromuscular disease mediated by anti
      acetylcholine receptor (AChR) autoantibodies, is associated with thymic
      hyperplasia characterized by ectopic germinal centers that contain pathogenic
      antibody-producing B cells. Our thymic transcriptome study demonstrated increased
      expression of CCL21, a recruiter of immune cells. Accordingly, we are
      investigating its implication in MG pathogenesis. METHODS: The expression of
      CCL21 and its CCR7 receptor was analyzed by enzyme-linked immunosorbent assay and
      fluorescence-activated cell sorting, respectively. Chemotaxis of T and B cells to
      CCL21 was measured by transwell assay. The nature of the thymic cells
      overexpressing CCL21 was investigated by immunochemistry and laser-capture
      microdissection combined with real-time PCR. RESULTS: We demonstrate that CCL21
      is overexpressed specifically in hyperplastic MG thymuses, whereas there is no
      variation in CCR7 levels on blood cells. We show that although CCL21 attracts
      both human T and B cells, it acts more strongly on naive B cells. CCL21
      overexpression is normalized in corticoid-treated MG patients, suggesting that
      targeting this chemokine could represent a new selective treatment, decreasing
      the abnormal peripheral lymphocyte recruitment. Moreover, we locate protein and
      messenger RNA overexpression of CCL21 to specific endothelial vessels.
      Investigation of the nature of these vessels demonstrated different angiogenic
      processes in MG thymuses: high endothelial venule angiogenesis and
      lymphangiogenesis. Unexpectedly, CCL21 overexpression originates from afferent
      lymphatic endothelial vessels. INTERPRETATION: We postulate that thymic
      overexpression of CCL21 on specialized lymphatic vessels results in abnormal
      peripheral lymphocyte recruitment, bringing naive B cells in contact with the
      inflammatory environment characteristic of MG thymuses, where they can be
      sensitized against AChR.

PMID- 19847901
TI  - SCARB2 mutations in progressive myoclonus epilepsy (PME) without renal failure.
AB  - OBJECTIVE: Mutations in SCARB2 were recently described as causing action
      myoclonus renal failure syndrome (AMRF). We hypothesized that mutations in SCARB2
      might account for unsolved cases of progressive myoclonus epilepsy (PME) without
      renal impairment, especially those resembling Unverricht-Lundborg disease (ULD).
      Additionally, we searched for mutations in the PRICKLE1 gene, newly recognized as
      a cause of PME mimicking ULD. METHODS: We reviewed cases of PME referred for
      diagnosis over two decades in which a molecular diagnosis had not been reached.
      Patients were classified according to age of onset, clinical pattern, and
      associated neurological signs into "ULD-like" and "not ULD-like." After exclusion
      of mutations in cystatin B (CSTB), DNA was examined for sequence variation in
      SCARB2 and PRICKLE1. RESULTS: Of 71 cases evaluated, 41 were "ULD-like" and five
      had SCARB2 mutations. None of 30 "not ULD-like" cases were positive. The five
      patients with SCARB2 mutations had onset between 14 and 26 years of age, with no
      evidence of renal failure during 5.5 to 15 years of follow-up; four were followed
      until death. One living patient had slight proteinuria. A subset of 25 cases were
      sequenced for PRICKLE1 and no mutations were found. INTERPRETATION: Mutations in
      SCARB2 are an important cause of hitherto unsolved cases of PME resembling ULD at
      onset. SCARB2 should be evaluated even in the absence of renal involvement. Onset
      is in teenage or young adult life. Molecular diagnosis is important for
      counseling the patient and family, particularly as the prognosis is worse than
      classical ULD.

PMID- 19847902
TI  - The graphemic/motor frontal area Exner's area revisited.
AB  - OBJECTIVE: In 1881, Exner first described a "graphic motor image center" in the
      middle frontal gyrus. Current psycholinguistic models of handwriting involve the
      conversion of abstract, orthographic representations into motor representations
      before a sequence of appropriate hand movements is produced. Direct cortical
      stimulation and functional magnetic resonance imaging (fMRI) were used to study
      the human frontal areas involved in writing. METHODS: Cortical electrical
      stimulation mapping was used intraoperatively in 12 patients during the removal
      of brain tumors to identify the areas involved in oral language (sentence reading
      and naming) and writing, and to spare them during surgery. The fMRI activation
      experiment involved 12 right-handed and 12 left-handed healthy volunteers using
      word dictation (without visual control) and 2 control tasks. RESULTS: Direct
      cortical electrical stimulation of restricted areas rostral to the primary motor
      hand area (Brodmann area [BA] 6) impaired handwriting in 6 patients, without
      disturbing hand movements or oral language tasks. In 6 other patients,
      stimulation of lower frontal regions showed deficits combining handwriting with
      other language tasks. fMRI also revealed selective activation during word
      handwriting in left versus right BA6 depending on handedness. This area was
      anatomically matched to those areas that affected handwriting on electrical
      stimulation. INTERPRETATION: An area in middle frontal gyrus (BA6) that we have
      termed the graphemic/motor frontal area supports bridging between orthography and
      motor programs specific to handwriting.

PMID- 19847903
TI  - Loss of hypocretin (orexin) neurons with traumatic brain injury.
AB  - Chronic, daytime sleepiness is a major, disabling symptom for many patients with
      traumatic brain injury (TBI), but thus far, its etiology is not well understood.
      Extensive loss of the hypothalamic neurons that produce the wake-promoting
      neuropeptide hypocretin (orexin) causes the severe sleepiness of narcolepsy, and
      partial loss of these cells may contribute to the sleepiness of Parkinson disease
      and other disorders. We have found that the number of hypocretin neurons is
      significantly reduced in patients with severe TBI. This observation highlights
      the often overlooked hypothalamic injury in TBI and provides new insights into
      the causes of chronic sleepiness in patients with TBI.

PMID- 19847905
TI  - Traumatic brain injury: a glimpse of order among the chaos?

PMID- 19847904
TI  - Androgenic suppression of spreading depression in familial hemiplegic migraine
      type 1 mutant mice.
AB  - Familial hemiplegic migraine type 1 (FHM1), a severe migraine with aura variant,
      is caused by mutations in the CACNA1A gene. Mutant mice carrying the FHM1 R192Q
      mutation exhibit increased propensity for cortical spreading depression (CSD), a
      propagating wave of neuroglial depolarization implicated in migraine aura. The
      CSD phenotype is stronger in female R192Q mutants and diminishes after
      ovariectomy. Here, we show that orchiectomy reciprocally increases CSD
      susceptibility in R192Q mutant mice. Chronic testosterone replacement restores
      CSD susceptibility by an androgen receptor-dependent mechanism. Hence, androgens
      modulate genetically-enhanced CSD susceptibility and may provide a novel
      prophylactic target for migraine.

PMID- 19847906
TI  - NerveCenter: media focus on 'miracle cure' for cerebral palsy pits science vs.
      hype.

PMID- 19847907
TI  - Bleak prospects for primary progressive multiple sclerosis therapy: downs and
      downs, but a glimmer of hope.

PMID- 19847909
TI  - Neuroradiological diagnosis of idiopathic normal-pressure hydrocephalus: the
      search for the Holy Grail.

PMID- 19847910
TI  - Calcium/calmodulin-dependent serine protein kinase and mental retardation.
AB  - Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane
      associated guanylate kinase protein family. The members of this protein family
      function as multiple domain adaptor proteins originally identified at cell
      junctions and synapses. Insertional mutations or targeted disruption of the CASK
      gene in mice results in neonatal lethality, indicating an important role for CASK
      in development. Recently, several reports have also indicated that mutations in
      the human CASK gene result in X-linked malformations of the brain and mental
      retardation. At the molecular level, many studies indicate that CASK is critical
      for synapse formation at both presynaptic and postsynaptic junctions, and in the
      regulation of gene expression. The known molecular functions of CASK explain, at
      least partially, mental retardation and brain developmental defects in patients.
      In this review, recent findings about CASK are summarized and discussed.

PMID- 19847908
TI  - Rituximab in patients with primary progressive multiple sclerosis: results of a
      randomized double-blind placebo-controlled multicenter trial.
AB  - OBJECTIVE: Rituximab, a monoclonal antibody selectively depleting CD20+ B cells,
      has demonstrated efficacy in reducing disease activity in relapsing-remitting
      multiple sclerosis (MS). We evaluated rituximab in adults with primary
      progressive MS (PPMS) through 96 weeks and safety through 122 weeks. METHODS:
      Using 2:1 randomization, 439 PPMS patients received two 1,000 mg intravenous
      rituximab or placebo infusions every 24 weeks, through 96 weeks (4 courses). The
      primary endpoint was time to confirmed disease progression (CDP), a prespecified
      increase in Expanded Disability Status Scale sustained for 12 weeks. Secondary
      endpoints were change from baseline to week 96 in T2 lesion volume and total
      brain volume on magnetic resonance imaging scans. RESULTS: Differences in time to
      CDP between rituximab and placebo did not reach significance (96-week rates:
      38.5% placebo, 30.2% rituximab; p = 0.14). From baseline to week 96, rituximab
      patients had less (p < 0.001) increase in T2 lesion volume; brain volume change
      was similar (p = 0.62) to placebo. Subgroup analysis showed time to CDP was
      delayed in rituximab-treated patients aged <51 years (hazard ratio [HR] = 0.52; p
      = 0.010), those with gadolinium-enhancing lesions (HR = 0.41; p = 0.007), and
      those aged <51 years with gadolinium-enhancing lesions (HR = 0.33; p = 0.009)
      compared with placebo. Adverse events were comparable between groups; 16.1% of
      rituximab and 13.6% of placebo patients reported serious events. Serious
      infections occurred in 4.5% of rituximab and <1.0% of placebo patients. Infusion
      related events, predominantly mild to moderate, were more common with rituximab
      during the first course, and decreased to rates comparable to placebo on
      successive courses. INTERPRETATION: Although time to CDP between groups was not
      significant, overall subgroup analyses suggest selective B-cell depletion may
      affect disease progression in younger patients, particularly those with
      inflammatory lesions.

PMID- 19847911
TI  - Historical perspective: neurological advances from studies of war injuries and
      illnesses.
AB  - Early in the 20th century during the Russo-Japanese War and World War I (WWI),
      some of the most important, lasting contributions to clinical neurology were
      descriptive clinical studies, especially those concerning war-related peripheral
      nerve disorders (eg, Hoffmann-Tinel sign, Guillain-Barre-Strohl syndrome [GBS])
      and occipital bullet wounds (eg, the retinal projection on the cortex by Inouye
      and later by Holmes and Lister, and the functional partitioning of visual
      processes in the occipital cortex by Riddoch), but there were also other
      important descriptive studies concerning war-related aphasia, cerebellar
      injuries, and spinal cord injuries (eg, cerebellar injuries by Holmes, and
      autonomic dysreflexia by Head and Riddoch). Later progress, during and shortly
      after World War II (WWII), included major progress in understanding the
      pathophysiology of traumatic brain injuries by Denny-Brown, Russell, and
      Holbourn, pioneering accident injury studies by Cairns and Holbourn, promulgation
      of helmets to prevent motorcycle injuries by Cairns, development of comprehensive
      multidisciplinary neurorehabilitation by Rusk, and development of spinal cord
      injury care by Munro, Guttman, and Bors. These studies and developments were
      possible only because of the large number of cases that allowed individual
      physicians the opportunity to collect, collate, and synthesize observations of
      numerous cases in a short span of time. Such studies also required dedicated,
      disciplined, and knowledgeable investigators who made the most out of their
      opportunities to systematically assess large numbers of seriously ill and injured
      soldiers under stressful and often overtly dangerous situations.

PMID- 19847912
TI  - Dopamine D2 receptor knockout mice develop features of Parkinson disease.
AB  - OBJECTIVE: This study questions whether increased dopamine (DA) turnover in
      nigral neurons leads to formation of Lewy bodies (LBs), the characteristic alpha
      synuclein-containing cytoplasmic inclusion of Parkinson disease (PD). METHODS:
      Mice with targeted deletion of the dopamine D(2) receptor gene (D(2)R[-/-]) have
      higher striatal and nigral dopamine turnover and elevated oxidative stress. These
      mice were examined for evidence of histological, biochemical, and gene expression
      changes consistent with a synucleinopathy. RESULTS: LB-like cytoplasmic
      inclusions containing alpha-synuclein and ubiquitin were present in substantia
      nigra pars compacta (SNpc) neurons of older D(2)R(-/-) mice, and were also
      occasionally seen in aged wild-type mice. These inclusions displaced the nucleus
      of affected cells and were eosinophilic. Diffuse cytosolic alpha-synuclein
      immunoreactivity in SNpc neurons increased with age in both wild-type and D(2)R(
      /-) mice, most likely because of redistribution of alpha-synuclein from striatal
      terminals to SNpc cell bodies. Gene and protein expression studies indicated
      endoplasmic reticulum (ER) stress and changes in trafficking and autophagic
      pathways in D(2)R(-/-) SNpc. These changes were accompanied by a loss of DA
      terminals in the dorsal striatum, although there was no evidence of progressive
      cell death in the SNpc. INTERPRETATION: Increased sprouting and DA turnover, as
      observed in PD and D(2)R(-/-) mice, augments LB-like inclusions and axonal
      degeneration of dopaminergic neurons. These changes are associated with ER stress
      and autophagy.

PMID- 19847915
TI  - Slow formation of aggregation-resistant beta-sheet folding intermediates.
AB  - Protein folding has been studied extensively for decades, yet our ability to
      predict how proteins reach their native state from a mechanistic perspective is
      still rudimentary at best, limiting our understanding of folding-related
      processes in vivo and our ability to manipulate proteins in vitro. Here, we
      investigate the in vitro refolding mechanism of a large beta-helix protein,
      pertactin, which has an extended, elongated shape. At 55 kDa, this single domain,
      all-beta-sheet protein allows detailed analysis of the formation of beta-sheet
      structure in larger proteins. Using a combination of fluorescence and far-UV
      circular dichroism spectroscopy, we show that the pertactin beta-helix refolds
      remarkably slowly, with multiexponential kinetics. Surprisingly, despite the slow
      refolding rates, large size, and beta-sheet-rich topology, pertactin refolding is
      reversible and not complicated by off-pathway aggregation. The slow pertactin
      refolding rate is not limited by proline isomerization, and 30% of secondary
      structure formation occurs within the rate-limiting step. Furthermore, site
      specific labeling experiments indicate that the beta-helix refolds in a multistep
      but concerted process involving the entire protein, rather than via initial
      formation of the stable core substructure observed in equilibrium titrations.
      Hence pertactin provides a valuable system for studying the refolding properties
      of larger, beta-sheet-rich proteins, and raises intriguing questions regarding
      the prevention of aggregation during the prolonged population of partially
      folded, beta-sheet-rich refolding intermediates. Proteins 2010. (c) 2009 Wiley
      Liss, Inc.

PMID- 19847916
TI  - Retraction: Open and closed conformations reveal induced fit movements in
      butyrate kinase 2 activation. J. Diao, Y. D. Ma, and M. S. Hasson.
AB  - The following article from Proteins: Structure, Function, and Bioinformatics,
      "Open and closed conformations reveal induced fit movements in butyrate kinase 2
      activation," by Jiasheng Diao, Yunglin D. Ma, and Miriam S. Hasson, published
      online on 21 October 2010 in Wiley Online Library (onlinelibrary.wiley.com), has
      been retracted by agreement between the journal Editor in Chief, Bertrand Garcia
      Moreno, and Wiley Periodicals. The retraction has been agreed because it was
      established by internal investigation performed by Purdue University that the
      authors of this article are not the owners of the data and have no right to
      publication.

PMID- 19847913
TI  - Characterization of intrinsically disordered proteins with electrospray
      ionization mass spectrometry: conformational heterogeneity of alpha-synuclein.
AB  - Conformational heterogeneity of alpha-synuclein was studied with electrospray
      ionization mass spectrometry by analyzing protein ion charge state distributions,
      where the extent of multiple charging reflects compactness of the protein
      conformations in solution. Although alpha-synuclein lacks a single well-defined
      structure under physiological conditions, it was found to sample four distinct
      conformational states, ranging from a highly structured one to a random coil. The
      compact highly structured state of alpha-synuclein is present across the entire
      range of conditions tested (pH ranging from 2.5 to 10, alcohol content from 0% to
      60%), but is particularly abundant in acidic solutions. The only other protein
      state populated in acidic solutions is a partially folded intermediate state
      lacking stable tertiary structure. Another, more compact intermediate state is
      induced by significant amounts of ethanol used as a co-solvent and appears to
      represent a partially folded conformation with high beta-sheet content. Protein
      dimerization is observed throughout the entire range of conditions tested,
      although only acidic solutions favor formation of highly structured dimers of
      alpha-synuclein. These dimers are likely to present the earliest stages in
      protein aggregation leading to globular oligomers and, subsequently,
      protofibrils.

PMID- 19847914
TI  - Mechanism of formation of the C-terminal beta-hairpin of the B3 domain of the
      immunoglobulin binding protein G from Streptococcus. III. Dynamics of long-range
      hydrophobic interactions.
AB  - A 20-residue peptide, IG(42-61), derived from the C-terminal beta-hairpin of the
      B3 domain of the immunoglobulin binding protein G from Streptoccocus was studied
      using circular dichroism, nuclear magnetic resonance (NMR) spectroscopy at
      various temperatures and by differential scanning calorimetry (DSC). Unlike other
      related peptides studied so far, this peptide displays two heat capacity peaks in
      DSC measurements (at a scanning rate of 1.5 deg/min at a peptide concentration of
      0.07 mM), which suggests a three-state folding/unfolding process. The results
      from DSC and NMR measurements suggest the formation of a dynamic network of
      hydrophobic interactions stabilizing the structure, which resembles a beta
      hairpin shape over a wide range of temperatures (283-313 K). Our results show
      that IG (42-61) possesses a well-organized three-dimensional structure stabilized
      by long-range hydrophobic interactions (Tyr50 ... Phe57 and Trp48 ... Val59) at T
      = 283 K and (Trp48 ... Val59) at 305 and 313 K. The mechanism of beta-hairpin
      folding and unfolding, as well as the influence of peptide length on its
      conformational properties, are also discussed.

PMID- 19847917
TI  - Molecular mechanism of allosteric communication in the human PPARalpha-RXRalpha
      heterodimer.
AB  - The peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear
      receptor (NR) that forms a heterodimeric transcription factor complex with the
      retinoid X receptor alpha (RXRalpha). The phenomenon that the heterodimer can be
      activated by both PPARalpha and RXRalpha ligands, while both ligands have a
      synergistic effect on its activity suggests that there is an allosteric
      communication within the heterodimer. In this study, the molecular mechanism of
      this allosteric signaling was studied by molecular dynamics (MD) simulations and
      some of the residues involved in this communication were tested experimentally.
      Multiple MD simulations were done for the PPARalpha-RXRalpha heterodimer ligand
      binding domains (LBDs) without ligands, with agonistic ligand bound to RXRalpha
      or PPARalpha, and ligand bound to both receptors. Fluctuation calculations and
      structural clustering analysis of the heterodimer MD simulations showed that
      ligand binding to RXRalpha decreases fluctuations of large parts of PPARalpha,
      most notably helices 3 and 4 at the coactivator binding site, which presumably
      stabilizes the coactivator binding to heterodimer complex. The dynamics of helix
      8-9 loop and helix 10/11 located at the heterodimeric interface were affected by
      RXRalpha ligand binding, suggesting that these parts of the dimer are involved in
      allosteric communication. Experimental data complemented this view by showing
      that a large set of residues at the heterodimerization surface has a role in the
      communication. These results provided evidence that RXRalpha ligand binding
      induced stabilization of PPARalpha coactivator binding site has a role in the
      permissive and synergistic activation of the PPARalpha-RXRalpha heterodimer.
      Proteins 2010. (c) 2009 Wiley-Liss, Inc.

PMID- 19847918
TI  - Echocardiographic identification of ventricular septal rupture caused by acute
      stent thrombosis.
AB  - Coronary stenting is an increasingly common procedure. Complications are rare.
      However, when they do occur, they often require urgent invasive treatment.
      Investigations that are critical for establishing a diagnosis as well as such
      guide treatment as a detailed assessment of myocardial morphology and function
      using transthoracic echocardiography may be overlooked in the haste to treat the
      patient. We present a case report of subacute drug-eluting stent thrombosis in
      which a meticulous echocardiographic examination allowed the identification of a
      ventricular septal rupture, which ultimately modified treatment.

PMID- 19847920
TI  - Structure of hyperthermophilic endocellulase from Pyrococcus horikoshii.

PMID- 19847921
TI  - Holo-BtuF stabilizes the open conformation of the vitamin B12 ABC transporter
      BtuCD.
AB  - While there is evidence that other ABC transporters can tell between empty and
      loaded substrate binding protein, reconstitution experiments suggest otherwise
      for the Escherichia coli vitamin B12 importer BtuCD-F. Here, we address the
      question of BtuCD-F substrate sensitivity in a combined protein-protein docking
      and molecular dynamics simulation approach. Starting from the BtuCD and holo-BtuF
      crystal structures, we model two holo-BtuCD-F docking complexes differing by a
      180 degrees orientation of BtuF. One of these is similar to the apo-BtuCD-F
      crystal structure. Both docking complexes were embedded in a lipid/water
      environment to investigate their dynamics and BtuCD's conformational response to
      the presence and absence of BtuF, vitamin B12, and Mg-ATP in a series of 28
      independent MD simulations. We find holo-BtuF stabilizing the open conformation
      of BtuCD, whereas the transporter begins to close again when BtuF or vitamin B12
      is removed-suggesting BtuCD-F is capable of substrate sensitivity. We identified
      BtuC transmembrane helices 3 and 5, the L-loops and the adjacent helices
      comprised of BtuC residues 170-180 as hotspots of conformational change. We
      propose the latter to act as substrate sensors. BtuF-Trp44 appears to act as a
      lid on the vitamin B12 binding cleft in BtuF X-ray structures and protrudes into
      the BtuCD transport channel in one of our simulations, which might represent an
      initial step in vitamin B12 uptake. On an average, we observe subunit motions
      where the nucleotide binding domains approach each other while the transmembrane
      domains display an opening trend toward the periplasm.

PMID- 19847922
TI  - Solid-state NMR and simulation studies of equinatoxin II N-terminus interaction
      with lipid bilayers.
AB  - The interaction with model membranes of a peptide, EqtII(1-32), corresponding to
      the N-terminal region of the pore-forming toxin equinatoxin II (EqtII) has been
      studied using solid-state NMR and molecular dynamics (MD) simulations. The
      distances between specifically labeled nuclei in [(19)F-para]Phe16-[1-(13)C]Leu19
      and [(19)F-para]Phe16-[(15)N]Leu23 analogs of EqtII(1-32) measured by REDOR in
      lyophilized peptide were in agreement with published crystal and solution
      structures. However, in both DMPC and mixed DMPC:SM membrane environments,
      significant changes in the distances between the labeled amino acid pairs were
      observed, suggesting changes in helical content around the experimentally studied
      region, 16-23, in the presence of bilayers. (19)F-(31)P REDOR experiments
      indicated that the aromatic ring of Phe16 is in contact with lipid headgroups in
      both membrane environments. For the DMPC:SM mixed bilayers, a closer interaction
      between Phe16 side chains and lipid headgroups was observed, but an increase in
      distances was observed for both labeled amino acid pairs compared with those
      measured for EqtII(1-32) in pure DMPC bilayers. The observed differences between
      DMPC and DMPC:SM bilayers may be due to the greater affinity of EqtII for the
      latter. MD simulations of EqtII(1-32) in water, on a pure DMPC bilayer, and on a
      mixed DMPC:SM bilayer indicate significant peptide secondary structural
      differences in the different environments, with the DMPC-bound peptide adopting
      helical formations at residues 16-24, whereas the DMPC:SM-bound peptide exhibits
      a longer helical stretch, which may contribute to its enhanced activity against
      PC:SM compared with pure PC bilayers. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

PMID- 19847923
TI  - Ecdysteroid receptor (EcR) is associated with microtubules and with mitochondria
      in the cytoplasm of prothoracic gland cells of Rhodnius prolixus (Hemiptera).
AB  - We have shown previously that EcR in larval Rhodnius is present in the cytoplasm
      of various cell types and undergoes daily cycling in abundance in the cytoplasm
      (Vafopoulou and Steel, 2006. Cell Tissue Res 323:443-455). It is unknown which
      organelles are associated with EcR. Here, we report that cytoplasmic EcR in
      prothoracic gland cells is associated with both microtubules and mitochondria,
      and discuss the implications for both nuclear and non-genomic actions of EcR. EcR
      was localized immunohistochemically using several antibodies to EcR of Manduca
      and Drosophila and a confocal laser scanning microscope. Double labels were made
      to visualize EcR and (1) microtubules (using an antibody to tyrosylated alpha
      tubulin) and (2) mitochondria (using a fluorescent MitoTracker probe), both after
      stabilization of microtubules with taxol. EcR co-localized with both tubulin and
      mitochondria. All the different EcR antibodies produced similar co-localization
      patterns. EcR was seen in the perinuclear aggregation of mitochondria, indicating
      that mitochondria are targets of ecdysone, which could influence mitochondrial
      gene transcription. EcR was also distributed throughout the microtubule network.
      Co-localization of EcR with tubulin or mitochondria was maintained after
      depolymerization of microtubules with colchicine. Treatment with taxol resulted
      in accumulation of EcR in the cytoplasm and simultaneous depletion of EcR from
      the nucleus, suggesting that microtubules may be involved in targeted
      intracellular transport of EcR to the nucleus (genomic action) or may play a role
      in rapid ecdysone signal transduction in the extranuclear compartment, i.e., in
      non-genomic actions of ecdysone. These findings align EcR more closely with
      steroid hormone receptors in vertebrates.

PMID- 19847926
TI  - I think I have hemorrhoids. How can I get rid of them?

PMID- 19847925
TI  - By the way, doctor. Recently, my dog bit me on the hand. When I showed up at my
      doctor's office several days later, he told me I had waited too long. Should I
      have gone to the doctor sooner?

PMID- 19847927
TI  - A mutation that creates a pseudoexon in SOD1 causes  familial ALS.

PMID- 19847924
TI  - Detecting rare variants for complex traits using family and unrelated data.
AB  - Large genome-wide association studies (GWAS) have been performed to detect common
      genetic variants involved in common diseases, but most of the variants found this
      way account for only a small portion of the trait variance. Furthermore,
      candidate gene-based resequencing suggests that many rare genetic variants
      contribute to the trait variance of common diseases. Here we propose two designs,
      sibpair and unrelated-case designs, to detect rare genetic variants in either a
      candidate gene-based or genome-wide association analysis. First we show that we
      can detect and classify together rare risk haplotypes using a relatively small
      sample with either of these designs, and then have increased power to test
      association in a larger case-control sample. This method can also be applied to
      resequencing data. Next we apply the method to the Wellcome Trust Case Control
      Consortium (WTCCC) coronary artery disease (CAD) and hypertension (HT) data, the
      latter being the only trait for which no genome-wide association evidence was
      reported in the original WTCCC study, and identify one interesting gene
      associated with HT and four associated with CAD at a genome-wide significance
      level of 5%. These results suggest that searching for rare genetic variants is
      feasible and can be fruitful in current GWAS, candidate gene studies or
      resequencing studies.

PMID- 19847928
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847929
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847930
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847931
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847933
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847932
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847934
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847935
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847936
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847937
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847938
TI  - Commentaries on viewpoint: pick your Poiseuille: normalizing the shear stimulus
      in studies of flow-mediated dilation.

PMID- 19847939
TI  - Will standardization of brachial artery shear stimulus make fmd ready for
      clinical "prime-time"?

PMID- 19847940
TI  - Shear rate may normalize the hyperemic flow response to the ischemic stimulus.

PMID- 19847941
TI  - [Measurement of publication performance].

PMID- 19847942
TI  - Natural disasters highlight gaps in preparedness.

PMID- 19847945
TI  - Aspects of human disease. 36. Cushing's disease.

PMID- 19847943
TI  - Recent advances in the assessment of myocardial viability.

PMID- 19847946
TI  - Calcium channel blockers: monotherapy and dual therapy considerations in the
      treatment of hypertension.
AB  - The papers in this supplement speak to several of the issues pertinent to
      contemporary therapy with CCBs. The article by Dr Weir thoughtfully describes
      important pharmacokinetic and pharmacodynamic features of CCBs. In so doing he
      establishes the basis for combination CCB and ACE inhibitor therapy. Dr Frishman
      provides a scholarly description of the cardiovascular effects of CCBs and
      further elaborates on the distinctiveness of the various CCB subclasses. Finally,
      Dr Bakris et al. provides data from INVEST (INternational VErapamil-Trandolapril
      STudy), which shows the particular utility of a CCB and ACE inhibitor combination
      in bringing elderly hypertensive patients with CAD to goal BP when monotherapy

PMID- 19847947
TI  - Calcium channel blockers: their pharmacologic and therapeutic role in
      hypertension.
AB  - The prevalence of hypertension is increasing steadily in the US, particularly
      among African Americans. It is now clear that a large proportion of patients are
      inadequately controlled, with many patients requiring at least two agents to
      achieve their target BP. Calcium channel blockers (CCBs), comprising two
      subclasses--dihydropyridines and nondihydropyridines--have been for many years
      one of the mainstays of hypertension therapy. However, the use of CCBs as
      monotherapy has recently been overshadowed by the introduction of newer classes
      of agents such as angiotensin receptor blockers. Examining the pharmacologic and
      clinical effects of CCBs in essential hypertension and among specific patient
      groups (e.g. African Americans, patients with renal disease) paves the way for
      understanding why these agents are currently enjoying a resurgence in popularity
      as the basis for several fixed-dose combination regimens that promise to improve
      BP control and reduce the risk of cardiovascular events.

PMID- 19847948
TI  - Molecular mechanisms of acid exposure in Barrett's esophagus.
AB  - Esophageal adenocarcinoma is one of the most deadly gastrointestinal tumors.
      Gastroesophageal reflux has been established as a major risk factor for
      esophageal adenocarcinoma and Barrett's esophagus, the condition in which the
      normal squamous cells of the esophagus are replaced by metaplastic, specialized
      intestinal cells that are predisposed to malignancy. Data from ex vivo and in
      vitro model systems suggests that acid exposure has pro-proliferative and anti
      apoptotic effects which may facilitate neoplastic progression of Barrett's
      esophagus. Such data have led some authorities to propose complete elimination of
      gastric acid production as a chemopreventive strategy for Barrett's patients.
      However, it is not clear whether the effects of acid exposure on proliferation
      and apoptosis are a direct result of the acid exposure itself, or whether they
      result indirectly from the effects of acid on inducing esophageal inflammation.
      Such distinction may help in optimizing the level of gastric acid suppression for
      the prevention of cancer in Barrett's esophagus. This report describes the
      molecular mechanisms whereby acid exposure directly and indirectly, through
      inducing inflammation, may contribute to the neoplastic progression of Barrett's
      esophagus and the potential role for acid suppression as a chemopreventive
      strategy in patients with Barrett's esophagus.

PMID- 19847949
TI  - Characteristic of milk whey culture with Propionibacterium freudenreichii ET-3
      and its application to the inflammatory bowel disease therapy.
AB  - After the screening of microorganism culture, the culture of Propionibacterium
      freudenreichii ET-3 in the milk whey (milk whey culture) was found to stimulate
      the growth of our own Bifidobacteria in the colon but not the growth of other
      microorganisms. One of the active substances was identified as 1,4-dihydroxy-2
      naphthoic acid (DHNA).In healthy volunteers, the ingestion containing milk whey
      culture significantly increased the population of Bifidobacteria to total fecal
      bacterium. In the TNBS-induced colitis model of rats, milk whey culture
      significantly accelerated the healing of the colitis in a dose-dependent manner.
      It has been reported that DHNA inhibited the lymphocyte infiltration through
      reduction of MAdCAM-1 in DSS colitis model of mice and that the ingestion of milk
      whey culture was effective in the treatment of ulcerative colitis in human pilot
      study. These findings suggest that milk whey culture is a useful prebiotic for
      the therapy of inflammatory bowel disease.

PMID- 19847950
TI  - Effects of repetitive deformation on intestinal epithelial cells.
AB  - The intestinal mucosa is subject to a variety of physical forces in a complex
      manner during normal gut function and in disease. Intestinal mucosal atrophy
      during some disease states is a troubling phenomenon that is only partially
      explained by nutritional parameters. Increasing evidence suggests the possibility
      that repetitive deformation engendered by peristalsis, villous motility, and
      interaction with luminal chyme may be trophic for the gut mucosa in normal
      function, but that the intestinal epithelial response to repetitive deformation
      may be altered by inflammatory or other states in which plasma or tissue
      fibronectin levels are increased.

PMID- 19847951
TI  - Interaction of VEGF to gastric low grade MALT lymphoma by Helicobacter heilmannii
      infection in C57/BL/6 mice.
AB  - Helicobacter heilmannii (Hh) has been clinically reported to have some relation
      to gastric low grade MALT lymphoma. Recently, we have formed the gastric MALT
      lymphoma in C57BL/6 mice. MATERIALS AND METHODS: C57BL/6 mice infected with Hh
      from cynomolgus monkey for more than 6 months were used. The macroscopic,
      immunohistochemical and electron microscopic observation was performed RESULTS:
      MALT lymphoma was formed in almost 100% of the infected mice. Increased VEGF-A
      and Flt-3 immunoreactivity was recognized. CONCLUSION: Hh was shown to be related
      to the formation of MALT lymphoma and VEGF is suggested to play a role in this
      lymphoma.

PMID- 19847952
TI  - The effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)
      propanoate], and naproxen on key pathogenic steps in NSAID-enteropathy in the
      rat.
AB  - BACKGROUND: The pathogenesis of NSAID-induced enteropathy may involve dual
      inhibition of the cyclooxygenase (1 and 2) and a topical effect with sequential
      increased intestinal permeability, development of inflammation and ulcers. It has
      been suggested that nitric-oxide donating drugs cause significantly less
      gastrointestinal injury by counteracting for NSAID-induced reductions in blood
      flow. AIMS: To compare the effects of AZD3582 [4-(nitroxy)butyl-(2S)-2-(6-methoxy
      2-naphthyl) propanoate], and naproxen on key pathogenic steps in NSAID
      enteropathy in the rat. METHODS: Single doses of AZD3582, naproxen (dose range 10
      300 micromol/kg) or vehicle were given to male Sprague Dawley rats. Intestinal
      permeability (51CrEDTA) and intestinal inflammation (granulocyte marker protein)
      was quantitated and ulcer counts made. RESULTS: Intestinal permeability (all
      doses) and inflammation (highest dose of the drugs) increased significantly from
      control levels following naproxen and AZD3582 and there was no significant
      difference between the drugs. Median ulcer counts were, however, significantly (p
      < 0.01) lower with AZD3582 (4 +/- 2) than with naproxen (17 +/- 4). CONCLUSIONS:
      Naproxen and AZD3582 are equally associated with increased small intestinal
      permeability and inflammation, which is the consequence of their topical effect.
      The reduced small bowel ulcer counts with AZD3582 accords with the suggestion
      that vascular factors are the main driving force for NSAID-induced ulcer
      formation.

PMID- 19847953
TI  - Association of polymorphism of TLR4 and CD14 genes with gastroduodenal diseases
      in Japan.
AB  - BACKGROUND: Host genetic factors may play a key role in determining the long-term
      outcome of the Helicobacter pylori infection. Toll like receptor 4(TLR4) and CD14
      mediated recognition of lipo-polysaccharide (LPS) is required for efficient
      recognition of Gram-negative bacterial infections. AIMS: We investigated the
      effects of common polymorphisms of TLR4 Asp299Gly, Thr399Ile and CD14 promoter 
      C159T on the risk of gastric cancer including its subtypes and clinicopathologic
      features. We also investigated the effects of these polymorphisms on histologic
      degree of H. pylori induced gastritis. SUBJECTS: The study was performed in 149
      gastric cancer (GC) cases [mean age 64.0 +/- 12.4, M:F = 109:40] and 94 patients
      without evidence of GC (mean age 64.1 +/- 12.3, M:F = 65:25, Peptic ulcer
      diseases = 43.6%, gastritis = 56.4%) as the control group. METHODS: TLR4
      Asp299Gly, Thr399Ile and CD14 promoter -C159T were determined by PCR-RFLP in all
      the patients. Gastritis scores of non-cancerous gastric mucosa were assessed
      according to the updated Sydney system in H. pylori-positive subjects (n = 174).
      RESULTS: The frequencies of CD14-260 TT and T carrier were significantly lower in
      patents with intestinal type gastric cancer than in controls (OR = 0.31;95% CI =
      0.12-0.78, OR = 0.38; 95% CI = 0.18-0.81, respectively) Compared with patients
      older than 61 years, the atrophy score in antrum was significantly lower in TT
      and CT patients. TLR4 Asp299Gly, Thr399Ile were not detected in all the patients.
      CONCLUSION: Our data suggest that CD14 promoter-159TT and T carrier were
      associated with lower risk of developing gastric mucosal atrophy in H. pylori
      infected patients more than 61 years of age, and these genotypes may reduce the
      risk of intestinal type gastric cancer and TLR4 Asp299Gly, Thr399Ile are very
      rare in the Japanese population.

PMID- 19847954
TI  - Endoscopic submucosal dissection using sodium hyaluronate, a new technique for en
      bloc resection of a large superficial tumor in the colon.
AB  - En bloc resection of superficial tumors in the colon is challenging but
      beneficial for the precise diagnosis and treatment. We have been using a novel
      technique of endoscopic submucosal dissection with a viscous substance, sodium
      hyaluronate, and a needle knife in combination with a small-caliber-tip
      transparent hood and succeeded in the endoscopic en bloc resection of large
      superficial tumors in the colon. We endoscopically treated superficial tumors
      larger than 20mm in diameter of the colon in 166 patients between June 1998 and
      March 2005. All the lesions were successfully resected endoscopically and en bloc
      resection was achieved in 77% of them. Even large superficial tumors in the colon
      can be resected in one piece by using this technique.

PMID- 19847955
TI  - Roles of cyclooxygenase-2 and prostaglandin E receptors in gastric mucosal
      defense in Helicobacter pylori-infected mice.
AB  - BACKGROUND/AIM: Helicobacter pylori (H. pylori) induces cyclooxygenase-2 (COX-2)
      expression. The aim of this study was to assess the roles of COX-2 and PGE2
      receptors (EPs) in gastric defense in H. pylori-infected mice. METHODS: Gastric
      lesions were induced by oral administration of 0.15N HCl in 60% ethanol
      (HCl/EtOH) to mice infected with H. pylori, and macroscopically evaluated 30 min
      later. Mice were administered NS-398 (COX-2 selective inhibitor) concomitantly
      with selective EP agonists 4 hours before HCl/EtOH challenge. RESULTS: H. pylori
      infection prevented the gastric damage induced by HCl/ EtOH, and this protective
      effect was abolished by NS-398. Selective agonists of EP1, EP2, and EP4, but not
      the EP3 agonist, reversed the inhibitory effect of NS-398 on prevention of damage
      by H. pylori infection. The EP4 agonist and EP2/EP4 agonists inhibited the
      increase in TNF-alpha mRNA expression and neutrophilic infiltration caused by NS
      398, respectively. CONCLUSION: COX-2-derived PGE2 may play an important role in
      resistance to HCl/EtOH damage in H. pylori-infected mice by activating EP1, EP2,
      and EP4.

PMID- 19847956
TI  - Spatial and functional relationship of GGAs and AP-1 in Drosophila and HeLa
      cells.
AB  - The GGAs [Golgi-localised, gamma-ear containing, ARF (ADP ribosylation factor)
      binding proteins] and the AP-1 (adaptor protein-1) complex are both adaptors for
      clathrin-mediated intracellular trafficking, but their relationship to each other
      is unclear. We have used two complementary systems, HeLa cells and Drosophila
      Dmel2 cells, to investigate GGA and AP-1 function. Immunoelectron microscopy of
      endogenous AP-1 and GGA in Dmel2 cells shows that they are predominantly
      associated with distinct clathrin-coated structures. Depletion of either GGA or
      AP-1 by RNAi does not affect the incorporation of the other adaptor into clathrin
      coated vesicles (CCVs), and the cargo protein GFP-LERP (green fluorescent protein
      lysosomal enzyme receptor protein) is lost from CCVs only when both adaptors are
      depleted. Similar results were obtained using HeLa cells treated with siRNA to
      deplete all three GGAs simultaneously. AP-1 was still incorporated into CCVs
      after GGA depletion and vice versa, and both needed to be depleted for a robust
      inhibition of receptor-mediated sorting of lysosomal hydrolases. In contrast,
      downregulation of major histocompatibility complex (MHC) class I by HIV-1 Nef,
      which requires AP-1, was not affected by a triple GGA knockdown. Thus, our
      results indicate that the two adaptors can function independently of each other.

PMID- 19847957
TI  - 100 years of biochemistry and molecular biology. The decade-long pursuit of a
      reconstituted yeast transcription system: the work of Roger D. Kornberg.

PMID- 19847958
TI  - Tax cuts for organs?

PMID- 19847959
TI  - Hippocrates and informed consent.

PMID- 19847961
TI  - President's Column. The butterfly effect and dentistry.

PMID- 19847960
TI  - Editorial. Collective efforts to combat early childhood caries.

PMID- 19847962
TI  - JCDA interview. Microbiologist in the world of dentistry. Interview by Natalie
      Ouellette.

PMID- 19847963
TI  - Let us be glad about change.

PMID- 19847964
TI  - [Travels and memory: the sciences in Spain before and after the Civil War].
AB  - This essay revisits the influence of the Junta para Ampliacion de Estudios (JAE),
      the effect in the trajectory of the Consejo Superior de Investigaciones
      Cientificas of JAE grants and scholarships policy for Spanish young graduates to
      study abroad. It proposes grantee's travel as a source of knowledge and its
      practices. It develops the argument that institutional memory, as that of ideas,
      is not blurred by either a civil war or a dictatorship, repressive as it was. It
      also suggests genealogy of scientific practices and training during the 20th
      century in Spain.

PMID- 19847965
TI  - [Networks in science: the "JAE" in the exile].
AB  - Junta para Ampliacion de Estudios created different academic centers and
      laboratories in Spain. In this way, JAE helped to create an intellectual network.
      These centers not only blessed interchanges, debates and the modernization of
      Spanish science and culture, but also contributed to establish a platform that
      worked as a bridge in the aftermath of the Spanish Civil War. This network made
      possible for republican scientists and intellectuals, to find new positions
      abroad, when the time for exile came.

PMID- 19847966
TI  - ["If a woman has a big head": physiognomy and feminine nature in an Assyro
      Babylonian text].
AB  - In Mesopotamia, the human body was understood as an object for divination, that
      is, a system of signs, which carried messages about the individual, and whose
      meaning had to be decoded by means of observation and interpretation. Taking the
      physiognomic series "Summa sinnistu qaqqada rabat" ("If a woman has a big head")
      as the main source of my article, I analyse, on the one hand, the processes that
      take part in the promotion of a particular perception of women based on a
      specific reading of the female body. On the other hand, I deal with the elements
      that characterize this female perception, basically, the image of the ideal woman
      centred on motherhood, and, in close relation to this, the dangers that threaten
      women's life during pregnancy.

PMID- 19847967
TI  - Bug breakfast in the bulletin: syphilis.

PMID- 19847968
TI  - Factsheet: boils and skin infections.

PMID- 19847969
TI  - Abstracts of the 2nd International Meeting on Minimal Residual Cancer, September
      19-22, 1998, Berlin, Germany.

PMID- 19847970
TI  - Efficient cobalt(II) phthalocyanine-catalyzed reduction of flavones with sodium
      borohydride.
AB  - Efficient and facile reductions of flavones with sodium borohydride (NaBH4)
      catalyzed by cobalt(II) phthalocyanines afford cis-flavan-4-ols in 89-97% yields.

PMID- 19847971
TI  - [Women, bodies, and Hebrew medieval medical literature].
AB  - This essay explores different views on the female body articulated within Hebrew
      medieval texts on women's health care. It also investigates whether texts also
      integrate women's own perceptions of their bodies, and of their needs and care. I
      have analysed how this genre of Hebrew literature understood two key issues in
      the construction of sexed bodies: menstruation and cosmetics.

PMID- 19847972
TI  - [Medical discourse, the cornerstone of the gender relations in contemporary
      times].
AB  - The concept of gender establishes not only a distinction between biological sex
      (natural data and the object of biological and medical knowledge) and social sex
      (constructed within and by power relations). As a category of analysis, it also
      allows us to research the area of tension which governs the mutual construction
      of both. This construction inevitably pervades language and its capacity to
      establish categories of thought in cultures. This paper will demonstrate how the
      conceptual and linguistic category of "woman" is one of the areas where this
      mutual construction may be found in the 19th century.

PMID- 19847973
TI  - [Diagnostic categories and gender: two examples in contemporary Spanish medicine,
      chlorosis and neurasthenia (1877-1936)].
AB  - Chlorosis and Neurasthenia are two classical examples of pathological
      dissociations and the difficulties involved in approaching their diagnosis using
      scientific-naturalistic criteria. In the realm of those difficulties, the study
      examines the androcentric viewpoint and the ideological perspective of
      Contemporary Spanish Medicine when addressing the feminine nature and women's
      pathologies. Moreover, based on the similarities with present-day pain and
      fatigue syndromes, the study underlines the need to review the clinical approach
      to these illnesses by attempting to overcome the existing biomedical limitations.

PMID- 19847974
TI  - Hospital strategies to engage physicians in quality improvement.
AB  - In the last decade, growing evidence that the quality of U.S. health care is
      uneven at best has prompted greater attention to quality improvement, especially
      in the nation's hospitals. While physicians are integral to hospital quality
      improvement efforts, focusing physicians on these activities is challenging
      because of competing time and reimbursement pressures. To overcome these
      challenges, hospitals need to employ a variety of strategies, according to a
      Center for Studying Health System Change (HSC) study of four communities-
      Detroit, Memphis, Minneapolis-St. Paul and Seattle. Hospital strategies include
      employing physicians; using credible data to identify areas that need
      improvement; providing visible support through hospital leadership; identifying
      and nurturing physician champions to help engage physician peers; and
      communicating the importance of physicians' contributions. While hospitals are
      making gains in patient care quality, considerably more progress likely could be
      made through greater alignment of hospitals and physicians working together on
      quality improvement.

PMID- 19847975
TI  - Financing American Indian health care: impacts and options for improving access
      and quality.
AB  - (1) Indian Health Service (HIS) per patient funding is less than half of national
      per capita health spending, and declined further between 2003 and 2006. (2) Under
      funding of the IHS system has led to explicit rationing of services to American
      Indian and Alaska Native patients, with many specialized services provided only
      for "life or limb threatening" conditions. (3) IHS patients report experiencing
      access barriers and rate the quality of care process substantially lower than do
      Medicaid beneficiaries, but most indicate they prefer to use IHS for their health
      care. (4) Options to increase the funding for American Indian and Alaska Native
      health care exist, but would impose higher costs on federal and state budgets and
      are unlikely to be feasible in the current economic environment. However, IHS
      might be able to make certain organizational changes that would increase
      efficiency and its ability to extend existing funding to cover more services.

PMID- 19847976
TI  - Proceedings and abstracts of the 12th International Magnesium Symposium, 22-25
      September 2009, Iasi, Romania.

PMID- 19847977
TI  - Proceedings of the International Ion Chromatography Symposium, September 21-24,
      2008, Portland, Oregon, USA.

PMID- 19847978
TI  - From surgeon-apothecary to statesman: Sun Yat-sen at the Hong Kong College of
      Medicine.
AB  - Despite being of peasant stock from a small village on the southern coast of
      China, Sun Yat-sen (1866-1925), the founder and first provisional president of
      the Republic of China, was exposed to Western education early in life. Educated
      first in Hawaii and then in the British Crown Colony of Hong Kong, he was
      influenced by Christianity, democracy and liberalism. It was the years of his
      tertiary education at the Hong Kong College of Medicine that moulded his ultimate
      destiny as the healer of a nation. This article examines the importance of this
      medical college and its two stalwarts, Sir Patrick Manson and Sir James Cantlie,
      in the transformation that shaped China's modern history.

PMID- 19847979
TI  - The Greenock medical martyrs of 1864-65.
AB  - In the nineteenth century it was not uncommon for doctors to die from infectious
      diseases, but the death of five young physicians in Greenock--one third of the
      medical profession in a medium-sized Scottish town--from epidemic typhus, during
      four consecutive months in 1864-65, was an unusual event. This paper describes
      the lives and backgrounds of these five doctors, whose deaths in the line of duty
      earned them the description 'medical martyrs'.

PMID- 19847980
TI  - The history of ergot of rye (Claviceps purpurea) I: from antiquity to 1900.
AB  - This article outlines the history of ergot of rye up to 1900. Ergot is a fungal
      disease that affects many grasses but is particularly damaging to rye. It occurs
      as the result of an infection by the parasitic organism Claviceps purpurea, which
      produces characteristic black spurs on the grass. When incorporated into grain,
      the ergot fungus can cause severe outbreaks of poisoning in humans called
      ergotism. There are two main clinical forms of toxicity, gangrenous and
      convulsive, where coma and death often supervene: the death rate for ergotism has
      been reported to be between 10 and 20 per cent in major outbreaks. Historical
      accounts note that ergot could accelerate labour, stop postpartum haemorrhage and
      inhibit lactation. At the end of the nineteenth century ergot was still regarded
      as a 'glorious chemical mess', but help would arrive in the early 1900s and the
      complex jigsaw would be solved.

PMID- 19847981
TI  - Was Maria de' Medici a diabetic patient?
AB  - Queen Maria de' Medici (1573-1642) died in a miserable, marasmic state.
      Infections, gangrene, weight loss, fatigue and respiratory problems suggest a
      progressive decompensation of a previously existing Type 2 diabetes. The lack of
      biochemical data, however, permits only circumstantial evidence of this
      hypothesis. The author proposes that the queen developed subclinical diabetes
      after the age of 45, when she became obese due to excessive eating and lack of
      exercise. With a clear familial predisposition, she could have become insulin
      resistant and chronically hyperglycaemic. The presence of an internal deviation
      of the left eye, visible on several late portraits, suggests a mononeuropathy of
      cranial nerve VI. Repeated skin infections and gangrene of the lower limbs during
      the last month of her life complete the clinical diagnosis. Hyperglycaemic
      ketosis with Kussmaul respiration without adequate treatment may have caused her
      death.

PMID- 19847982
TI  - Bonded reverse phase ion exchange columns for the liquid chromatographic
      separations of neutral and ionic organic compounds.
AB  - Octadecylsilane was chemically bonded in situ on cation and anion exchange
      packings. The columns were tested for the liquid chromatographic separations of
      neutral and charged organic solutes which included nucleotides, polynuclear
      aromatic hydrocarbons, amines, carboxylic acids, and organometallic compounds.
      While some separations were effected predominantly by either the ion exchange
      sites or the reverse phase moieties, most separations appeared to be the combined
      effects of both stationary phases. The reverse phase partitioning, apparently
      induced by the solvophobic interaction, can make the elution volume and order of
      a charged solute significantly different from that found in a conventional ion
      exchange column. The mixed mode of ion exchange and reverse phase solvophobic
      interactions are illustrated.

PMID- 19847983
TI  - Entropy dominated high performance liquid chromatographic separations of
      polynuclear aromatic hydrocarbons. Temperature as a separation parameter.
AB  - The effect of temperature variations on the thermodynamic distribution behaviour
      in a silica C18/aqueous acetonitrile chromatographic system of polynuclear
      aromatic hydrocarbons is discussed. Evaluated enthalpy and calculated entropy
      change values are presented. The elution sequences of some polynuclear aromatic
      hydrocarbons are reversed by temperature variations, which ascribed to domination
      by entropy effects.

PMID- 19847984
TI  - Investigation of the system: tri-n-butyl phosphate-n-tetradecane by gas-liquid
      chromatography.
AB  - The interaction of tri-n-butyl phosphate (TBP) with various solutes has been
      investigated by gas-liquid chromatography (GLC). In the case of benzene and
      chloroalkane solutes, the formation of 1:1 complexes has been assumed. The
      nonlinear behaviour of partition coefficients of the solutes with high TBP
      concentration in an inert solvent (n-tetradecane) has been explained in terms of
      the dimerization of TBP. Infinite dilution activity coefficients of the solutes
      and the corresponding excess partial molar functions have also been determined
      between 25.00 and 50.00 degrees C in increments of 5 degrees C.

PMID- 19847985
TI  - An exploration of experimental parameters in the analysis of epoxy resin by
      reverse phase liquid chromatography.
AB  - Reverse phase liquid chromatographic methods have been developed for the quality
      control of epoxy resin formulations. The results show that different formulations
      require different instrumental parameters for optimun separation and detection.
      Operating parameters required for the analysis of complex mixtures of epoxy
      resins, which include curing agents and diluents, are described in this paper.
      Parameters found to be critical are column temperature, solvent flow rate and
      gradient, and detector wavelength. Microprocessor parameters required to obtain
      reproducible data are also discussed.

PMID- 19847986
TI  - Determination of aliphatic and aromatic aldehydes in polluted airs as their 2,4
      dinitrophenylhydrazones by high performance liquid chromatography.
AB  - A reversed-phase high performance liquid chromatography system with a LiChrosorb
      RP-18 column and acetonitrile-water mobile phase has been applied to the
      determination of C1-C6 aliphatic and aromatic aldehydes in polluted airs such as
      urban air, industrial emission, auto exhaust, and tobacco smoke. The aldehydes in
      a sample were allowed to react with 2,4-dinitrophenylhydrazine to form 2,4
      dinitrophenylhydrazone derivatives. The derivatives were extracted with
      chloroform and concentrated. The residue in acetonitrile was analyzed by high
      performance liquid chromatography. The derivatives of C1-C6 aliphatic aldehydes
      could be separated from the derivatives of the same molecular weight ketones, and
      aromatic aldehydes such as benzaldehyde, and isomers of tolualdehydes could be
      separated without effects of aliphatic carbonyl compounds. The aldehydes in the
      low ppm or ppb levels in air samples could be determined with good accuracy.

PMID- 19847987
TI  - Studies on thermal degradation of aromatic polyesters by pyrolysis-gas
      chromatography.
AB  - Thermal degradation of aromatic polyesters (see text for formula) (m = 2, 3, 4,
      5, and 6) was studied by pyrolysis/gas chromatography using a Curie-point
      pyrolyzer directly attached to a gas chromatograph with a thermally stable polar
      separation column (Thermon-1000) to cover a wide range of the degradation
      products. The characteristic peaks appearing on the pyrograms were identified
      using a mass spectrometer with a chemical ionization source which was also
      directly attached to the gas chromatograph. On the basis of the observed
      pyrograms, the common degradation mechanisms of the aromatic polyesters were
      discussed.

PMID- 19847988
TI  - An improved method of determining vapor-liquid equilibria for dilute organics in
      aqueous solution.
AB  - Chromatographic quantitative analyses of aqueous samples containing dilute
      concentrations of organic solutes are frequently confounded by sorption
      phenomena, particularly for vapor samples and aged syringes. A novel apparatus
      was developed for overcoming this problem; it utilizes continual circulation of
      gas through a thermostated syringe for sampling, followed by a needleless
      injection into the chromatograph. Precision and reproducibility well under 0.5%
      can be obtained in this way. This method was applied to a determination of the
      solubility of isopentyl acetate in water (2600 ppm) by following the equilibrium
      vapor response for increasing liquid concentrations. It was also used to
      determine equilibrium partition coefficients for C1-C5 n-acetates between air and
      water, over a range of temperatures from 25 to 40 degrees C.

PMID- 19847989
TI  - A capillary gas chromatographic inlet for the analysis of trace concentrations of
      compounds.
AB  - An important consideration in glass capillary column gas chromatography is the
      choice of the best sample inlet system for either splitting or splitless
      injection. This paper describes a simple direct glass-lined inlet, and describes
      its advantages over conventional split and splitless injection systems for trace
      component analysis. Several analyses are described which illustrate the
      superiority of the new direct inlet for these applications. The design of the new
      direct inlet system is such that column efficiency is not impaired and is
      equivalent to that of split injections.

PMID- 19847990
TI  - Ageing of columns of homogeneous mixed stationary phases in gas chromatography.
AB  - Chromatographic columns of homogeneous mixed phase prepared with squalane and
      polyethylene glycol 1540 have been subjected to an ageing process of about 1700
      hours at 100 degrees C followed by a similar period of time at 120 degrees C.
      Little change is observed at the lower temperature, while at 120 degrees C, a
      selective loss of the most volatile component of the mixture seems to occur,
      producing changes in the values of the retention indices obtained.

PMID- 19847991
TI  - Variation of retention volume with molecular weight of polyethylene glycol and
      with carbon number of n-alkanols.
AB  - Analysis of McReynolds' data for n-alkanols on polyethylene glycols of various
      molecular weights shows a continuous variation in retention properties up to
      molecular weights greater than 6000 and probably greater than 20,000. It is
      concluded that polyethylene glycol used as a "standard" stationary phase should
      have either very high or closely controlled molecular weight. The relation
      between log Vg and carbon number of the alkanol is nonlinear at C4 and below with
      negative deviations around 10% for C2 and C3 and a positive deviation of 25% for
      C1.

PMID- 19847992
TI  - Separation of conformational isomers of bouvardin by high-pressure liquid
      chromatography.
AB  - Bouvardin, a bicyclic hexapeptide, was found to exhibit a solvent-dependent
      conformational distribution. HPLC was utilized to separate the two different
      conformers whose distribution ratio was dependent on the solvent of injection.

PMID- 19847993
TI  - HPLC cassettes--a new modular separation system with high flexibility.
AB  - A new HPLC system is described wherein the column is used in the form of a
      cassette. The system includes a novel, problem-free column connection technique
      (needle seal). The column is not fitted with the usual single inlet and single
      outlet, but with a system of four combined inlets/outlets. These features provide
      on the one hand simple operation (e.g., rapid column exchange--no tools needed)
      and increased performance (e.g., no loss of separating power in the ancillary
      equipment), and on the other hand, a high degree of flexibility (e.g., convenient
      column backflush, improved sample splitting, simple eluate splitting, elegant
      post-column derivatization, and easy column switching).

PMID- 19847994
TI  - Technical note: a method for the preparation of glass multicapillary columns.

PMID- 19848018
TI  - [Dominique Larrey in Spain (1808-1809)].

PMID- 19848019
TI  - [How will the professional education reform of hospital personnel be received?].

PMID- 19848020
TI  - [Obtaining a nursing aide diploma by validation of acquired experience, current
      scene].

PMID- 19848021
TI  - [LMD, validation of acquired experience and the re-engineering of diplomas,
      differences and similarities].

PMID- 19848022
TI  - [Validation of acquired experience in operating room nursing, an opportunity?].

PMID- 19848023
TI  - Picture to parameters of information: journey on echo highway.

PMID- 19848025
TI  - Prime time use of tissue Doppler echocardiography: what have we gained?
AB  - In daily practice, Tissue Doppler Echocardiography (TDI) is used to estimate left
      ventricular filling pressures, categorize diastolic dysfunction, identify
      patients with heart failure (HF) with normal ejection fraction, differentiate
      constrictive pericarditis from restrictive cardiomyopathy, to prognosticate acute
      coronary syndrome, valvular heart disease syndrome of HF etc, correlate exercise
      capacity and symptoms, differentiate physiological versus pathological
      hypertrophy, assessment of intraventricular dyssynchrony, regional and global
      systolic and diastolic properties, detection of right ventricular function and
      possible carriers of genetic cardiomyopathies like Fabry's disease and
      hypertrophic cardiomyopathy, etc. Its role in adding incremental value to stress
      echocardiography, subclinical dysfunction evaluation, cardiac transplant
      rejection, cardiotoxicity of anti-cancer drugs, predicting occurrence and
      reversion of atrial fibrillation, predicting aortic catastrophies etc, although
      very encouraging has not found many users. It was intuitively considered
      invaluable in detecting subclinical myocarditis, acute rheumatic fever, Chaga's
      disease and localization of atrioventricular accessory pathways with manifest
      conduction, but could not find prime time readiness. In a similar manner, tissue
      velocity derived deformation parameters have not found prime time use, despite
      making great inroads into the mysteries of muscle mechanics. Part of the problem
      lies in their emphasis on unidirectional information of a structure which is
      essentially multidimensional. The other problems have been angle-dependency and
      low signal-to-noise ratio in deformation imaging which has restricted its use to
      highly experienced operators rather than more democratic use. Validation studies
      did indicate its great potential. TDI-derived imaging paved the way for non
      Doppler multidimensional deformation imaging which is slowly gaining ground.

PMID- 19848024
TI  - Three-dimensional echocardiography--state-of-the-art.

PMID- 19848026
TI  - Assessment of myocardial viability with contrast echocardiography.

PMID- 19848027
TI  - Contrast echocardiography for left ventricular opacification.
AB  - Intravenous contrast agents are clinically useful for objective assessment of
      left ventricular (LV) regional and global function in patients with sub-optimal
      echocardiography images. Recent concerns over the safety of second generation
      microbubble contrast agents have now been largely abated with the emergence of
      robust clinical data supporting its safety and clinical utility. With proper
      technique and use of available imaging modalities, contrast can help eliminate
      technically difficult examinations. This review highlights the concepts and
      techniques for intravenous contrast for LV opacification, clinical utility,
      relative merit in assessing structural and functional abnormalities of the left
      ventricle and the evolving applications in assessing two-dimensional (2D) LV
      intracavitary flow sequence during phases of cardiac cycle. Integration of a
      variety of imaging techniques including 3D echocardiography and newer
      applications such as echo particle imaging velocimetry promise to improve
      diagnostic application of intravenous contrast for defining new markers for
      cardiac function.

PMID- 19848028
TI  - Cardiac deformation imaging by echocardiography: fundamentals, applications, and
      new horizons.

PMID- 19848029
TI  - Reimbursement cuts, payment delays threaten ED bottom lines.
AB  - The best way to limit the damage to your department from arbitrary insurance
      reimbursement reductions and delays is to be proactive. Learn all you can about
      the appeals process and be on guard for subtle signs that the insurer's payment
      procedures may have changed without any formal announcement. * When negotiating a
      contract, be sure to have a billing and coding expert accompany you. * Regularly
      compare your volume statistics with your revenues to spot sudden substantial
      discrepancies. * If you suspect a change in reimbursement procedures, conduct a
      random audit of at least 100 charts.

PMID- 19848030
TI  - Palliative program yields triage changes in the ED.
AB  - Ensuring a smooth transition when your hospital adds a palliative care program
      can help improve throughput in your department while enhancing patient care and
      flow throughout for the facility. Here are some key steps for you to take: *
      Develop and/or obtain from the palliative care department a set of triage
      triggers for palliative care admission and palliative care consults. *
      Communicate the triggers to your staff. Post the triggers prominently, and
      publicly recognize physicians who are using them on a regular basis. * Make sure
      ancillary department staff such as social workers and chaplains are available for
      lengthy consultations with family members.

PMID- 19848031
TI  - Pharmacist in ED slashes medication errors by 50%.
AB  - Adding a pharmacist to your ED staff can improve cost efficiency, reduce the time
      it takes to have drugs available for patients, and aid in compliance with
      accreditation standards for medication review. * Standardized treatment for
      common diseases and conditions helps ensure that drugs will be readily available
      at all times. * On-staff pharmacist will review medications prospectively and
      retrospectively, helping your department comply with requirements from The Joint
      Commission. * Pharmacist's recommendations on product standardization will enable
      you to consolidate your drug supplies.

PMID- 19848032
TI  - ED's 'Pals' help put focus back on patients.
AB  - If your department's new electronic medical record is slowing down your patient
      flow and hindering staff communication, provide your physicians with interns from
      a local nursing school to handle the electronic charting and other documentation.
      Your ED will benefit from: * improved patient satisfaction scores, reduced left
      without-being-seen (LWBS) rates, and faster throughput; * improved communication
      between physicians and nurses; * a steady supply of future nurses who are well
      versed in ED practices and the preferences of staff physicians.

PMID- 19848033
TI  - ED uses 'Virtual ICU' to improve patient care.
AB  - The use of remote monitoring and patient consultation can ease the caseload
      burden of your staff, improve the flow of resuscitative therapies, and help
      relieve the pressure on other departments in the hospital. * You can use
      technology and additional off-site staff to monitor progress of sepsis care,
      glucose control, and blood pressures. * Off-site intensivists also can serve as
      back-up by responding to staff requests to review steps they have taken in
      patient care. * Patients who otherwise would have been admitted into the
      intensive care unit may be resuscitated and discharged directly from the ED.

PMID- 19848034
TI  - 'Plain talk' is best when dealing with disasters.
AB  - Communicating in a clear manner with local agencies during a disaster is critical
      to making sure your department gets what it wants, when it wants it. Here are
      some tips to ensure smoother communication: * Tell the agency exactly what you
      need for the short term - for example, six to 12 hours. * When describing your
      situation, include details about how it is affecting the ability of your
      department to function properly. * Participate in tabletop exercises and other
      emergency management drills so you can begin to establish an understanding with
      the people to whom you will talk.

PMID- 19848035
TI  - [Paracelsus--why is his work interpreted so diversely?].
AB  - Few historical figures have been as diversely interpreted as the 16th century
      Swiss physician Paracelsus. Celebrated by some as the founder of modern medicine,
      accused by others as an obstacle to the development of medical science. The aim
      of this essay is partly to provide a description of the life and work of
      Paracelsus. The main focus however, lies at deepening the understanding of the
      different interpretations of Paracelsus, and to deliver a reasonable answer as to
      how they might have evolved. A categorisation of the commentators on Paracelsus
      into three different groups is made. The individual arguments for each of these
      groups of commentators are described and to some extent also categorised.
      Finally, four models of explanation are introduced in an attempt to answer why
      Paracelsus has become so diversely interpreted by the historians of medicine.

PMID- 19848037
TI  - [Medicine on mission: The international health reform of Seventh-Day Adventists
      and their health care facilities in Sweden].
AB  - The international non-conformist denomination, Seventh-day Adventists, have since
      their foundation in 1863, had a distinctive health care model for their members.
      The life-style has included vegetarian diet, abstinence from alcohol, tobacco and
      other drugs and the observance of a day of rest once a week. The health policy
      has striven to care for God's creation in the hope of resurrection at the Day of
      Judgment and to reform the conventional medical practice. The Adventists have
      pursued an extensive international health care system--from the start based on
      dietary and physical treatment methods, such as hydrotherapy, massage and
      physiotherapy--in line with the Christian mission. Health care establishments
      have been inaugurated around the world as a vehicle for enabling the Christian
      health care message to reach the upper classes. With Adventist and Doctor, John
      Harvey Kellogg's Battle Creek Sanatorium in Michigan as both inspirational source
      and educational institution, the health care mission--including a vegetarian
      health food industry, following in the footsteps of cornflakes--spread to the
      Nordic countries by the turn of the century, 1900. Skodsborgs Badesanatorium near
      Copenhagen became the model institution for several health care establishments in
      Sweden during the 1900's, such as Hultafors Sanatorium. The American-Nordic link
      has manifested itself through co-publication of papers, exchange of health care
      personnel and reporting to the central Adventist church. The American non
      conformist domain as well as a private sphere of activity, aiming mainly from the
      outset at society's upper classes, has encountered certain difficulties in
      maintaining this distinction in Sweden's officially increasing secularised
      society, and in relation to a state health insurance and a publicly financed
      health care system. With the passing of time, the socioeconomic composition of
      patients at Hultafors became more heterogeneous, and conventional medical
      procedures were increasingly incorporated into the array of treatment resources.
      The successful enterprises--as they had been for a considerable time--could not,
      at the end of the 20th century, continue to be self financing or fulfil the
      missionary objectives among the upper classes. The institutionalised health care
      apparatus came to an end around the turn of the century, which also included the
      sale of health associated food product companies. The Seventh-day Adventist's
      combination of medicine and religion with Christian missionary aims have indeed,
      not only steered health care models and institutions worldwide, but also which
      target groups to mainly turn to, the specific treatment philosophy, desirable
      working environment and which medical technologies to use. Furthermore, the
      Adventist's health reform and care of the sick provide an example for how
      different medical cultures influence each other and develop in relation to one
      another in a pluralistic medical market. The developments are not merely a
      reflection of the medical, scientific and technical advancements, but also of the
      medical market's structure, financing and (inter)national connections, of
      religion, culture and not least of all, patients' options and their choices.

PMID- 19848036
TI  - [Per Henrik Ling and his impact on gymnastics].
AB  - Per Henrik Ling (1676-1839) is one of the most wellknown Swedes of all times. He
      studied different subjects and became a fencing-master. After studies of the
      antique Greece and, above all, after being informed of the German physical
      functional training, he created the Swedish gymnastics, in part according to
      antique model. In 1813 he founded the Gymnastic Central Institute in Stockholm
      with the obligation to educate gymnastic teachers for military and school needs.
      He was a versatile person, lively, sensitive, original and choleric with intense
      manners, excellent judgement and an extraordinary pedagogic capability.
      Therefore, a great deal of attention was paid to his work. However, he was also
      called eccentric, overstrung, touchy and stubborn. Ling had a high work capacity,
      but it deteriorated little by little during his last two decades. Obviously, the
      cause was his lingering joint pains (rheumatoid arthritis?), which impeded his
      physical activities, but above all his fatal lung tuberculosis. His reports on
      gymnastic subjects are remarcably few. Ling was also a prolific author of pure
      literature. He was appointed professor in 1825, fellow of the Swedish Medical
      Society in 1831 and member of the Swedish Academy in 1835. The gymnastics had
      four categories: pedagogic, military, medical and aesthetic. All movements should
      be performed correctly under a leader's direction. Free standing exercises in
      group were introduced and they were advantageous pedagogically as well as
      practically over the earlier predominant training. The medical gymnastics played
      an important, later even dominant, role in Ling's daily work but he could
      interest only a few physicians in his sphere. After Ling's death the medical
      gymnastics was exposed to a strong and entitled critique and little by little it
      became modernized. Also his pedagogic gymnastics was scrutinized and successively
      modified, and it can still be traced in some modern programs of physical
      training.

PMID- 19848038
TI  - Beyond a safety breakthrough. Interview by Haydn Bush.

PMID- 19848039
TI  - Rules for O.R. reps.

PMID- 19848040
TI  - Pricing forecast: cloudy.

PMID- 19848041
TI  - Cohesive effort cuts infections.

PMID- 19848042
TI  - The costs of confidentiality.

PMID- 19848043
TI  - Troubleshooting sterilization.

PMID- 19848044
TI  - Leverage SPD quality improvements by following the IOM's six aims.

PMID- 19848045
TI  - Liraglutide in type 2 diabetes: from pharmacological development to clinical
      practice.
AB  - The novel drug class of GLP-1 analogues is extremely promising, since existing
      evidence suggests they can address many of the unmet needs of diabetes treatment,
      i.e., long-term efficacy, low risk of hypoglycemia, cardiovascular protection,
      weight loss, long-term safety and tolerability. Besides the already available
      exenatide, liraglutide is expected to arrive soon on the market. It is a human
      GLP-1 analogue with high homology (97%) to native hormone. A comprehensive phase
      III evaluation consisting of six randomized clinical trials--the "Liraglutide
      Effect and Action Diabetes (LEAD) program"--was recently completed, involving
      6500 people seen in 600 sites in 41 countries worldwide. Aim of the LEAD program
      was to evaluate efficacy and safety of liraglutide as monotherapy and in
      combination with commonly used antidiabetic drugs. In all studies, once-daily
      liraglutide was well tolerated, significantly improved metabolic control, and
      reduced body weight, with low rates of hypoglycemia. Transient nausea was the
      most common side effects. Additional beneficial effects ofliraglutide on beta
      cell function, systolic blood pressure, and cardiovascular risk were also
      documented. If these encouraging results will be confirmed by long-term studies,
      liraglutide will acquire a prominent role among the main therapeutic options not
      only as add-on treatments in case of secondary failure, but also as an early
      strategy to reduce the burden of diabetes and its complications.

PMID- 19848046
TI  - Airway clearance therapy in cystic fibrosis patients.
AB  - Cystic fibrosis (CF) is the most common life-shortening inherited disease
      affecting Caucasian people. In CF, the major feature of lung disease is the
      retention of mucus due to impaired clearance of abnormally viscous airway
      secretions. Airway clearance techniques (ACTs) may significantly improve
      mucociliary clearance and gas exchange, thereby being of clinical benefit in
      reducing pulmonary complications in CF patients. ACTs include conventional chest
      physiotherapy, active cycle of breathing techniques, autogenic drainage, positive
      expiratory pressure and high-frequency chest compression. In order to suit the
      needs of patients, families and care-givers, ACTs need to be individually and
      continuously adapted.

PMID- 19848047
TI  - Sedentary lifestyle in active children admitted to a summer sport school.
AB  - Aim of this study was to investigate the sedentary patterns of school-aged active
      children admitted to a summer sport school. One hundred-twelve children aged 9-11
      years were interviewed through a questionnaire about sedentary behaviours and
      nutrition habits. Seventy-one per cent of children reported they watch TV seven
      days a week, girls less than boys (84 +/- 45 minutes vs. 110 +/- 75 minutes) (t =
      2.056; p = 0.042). The habit of TV viewing during meals was widespread (38%
      breakfast, 31% lunch, 62% dinner, 18% every meal). The prevalence of overweight
      or obesity (58.5%) was significantly higher among boys watching TV at dinner
      compared to the boys viewing TV only in the afternoon (35%) (chi2 = 4.976; p =
      0.026). Fifty-seven per cent of children (65% boys) were accustomed to nibble
      snacks during TV viewing, and this habit was widespread in overweight or obese
      boys (chi2 = 4.546; p = 0.033). The dietary patterns of children watching TV
      include more snack foods and fewer fruits than the dietary patterns of the same
      children exercising (chi2 = 4.199 p = 0.040). Also in active children the habit
      to watch television is widespread and, in spite of the tendency to physical
      activity, 46% of them were overweight or obese; in fact the time spent looking at
      a TV may be associated to overweight/obesity and this relationship could be
      explained by the amount of high-density foods consumption during inactivity.
      Playing video games, read a book and listening to music are sedentary lifestyle
      patterns but these seem not to represent a risk factor for an increased BMI.

PMID- 19848048
TI  - Adiponectin, IL-10 and metabolic syndrome in obese children and adolescents.
AB  - The metabolic syndrome (MetS) is a common basis for the development of
      atherogenic cardiovascular disease. Adiponectin has been demonstrated to be
      insulin-sensitizing and an anti-atherogenic factor and is considered a key
      ofMetS. It was suggested that IL-10 may be involved in the inflammatory network
      of MetS in relation to adiponectin. We examined the relationship between
      adiponectin, IL-10 and MetS in pediatric obese patients. MetS components were
      assessed in 70 severely obese and 30 non-obese children and adolescents. Serum
      levels of adiponectin and IL-10 were measured in these subjects. Serum
      adiponectin levels were significantly lower (p < 0.001) and levels of IL-10 were
      significantly higher (p = 0.012) in obese subjects. MetS was present in 35.71% of
      obese patients. Patients with MetS showed a borderline significant decrease in
      serum adiponectin levels and significantly increased IL-10 levels when compared
      to those without MetS (p = 0.051 and p = 0.031, respectively); the differences in
      adiponectin and IL-10 values were controlled to the effect of BMI. No correlation
      between adiponectin and IL-10 levels was found. Our obese children showed
      hypoadiponectin and hyper-IL10 values. MetS was not associated with low IL-10. We
      probably observe a first phase of the complex mechanism implicated in the
      development of the MetS in children.

PMID- 19848049
TI  - A pilot study of nalbuphine versus tramadol administered through continuous
      intravenous infusion for postoperative pain control in children.
AB  - Nalbuphine and tramadol are potent analgesic drugs. Our aim was to preliminarily
      assess and compare the efficacy and safety of nalbuphine and tramadol for
      postoperative analgesia in children. In a double-blind design, 24 ASA 1-3
      children aged 1 to 10 years undergoing a scheduled surgical procedure were
      randomly allocated to receive either an intravenous bolus dose of nalbuphine 100
      microg/kg immediately before the end of surgery followed by an infusion of 0.2
      microg/kg/min for 72 hrs., or an intravenous bolus dose of tramadol 1000
      microg/kg followed by an infusion of 2.0 microg/kg/min for 72 hrs. Postoperative
      pain control and drug-related adverse events were recorded. Three children who
      received nalbuphine required an extra bolus dose within the 12 hrs. of post
      surgery versus one child in the tramadol group. A similar number of patients in
      both groups required an increment in the infusion rate within the 72 post-surgery
      hours. Sedation was observed in 2 children in the nalbuphine group and in 1 child
      in the tramadol group. Four children presented vomiting with tramadol and two
      with nalbuphine. Cardiovascular parameters remained within the normal ranges in
      both groups. In conclusion, the bolus/infusion regimen of tramadol evaluated in
      this study appears to have better postoperative analgesic efficacy than the
      bolus/infusion regimen of nalbuphine. These preliminary results require further
      confirmation by studies with a sample size enough to clearly identify differences
      in their efficacy as well as in the rate of adverse events secondary to the
      administration of each of them.

PMID- 19848050
TI  - Beneficial effect of camel milk in diabetic nephropathy.
AB  - Diabetic nephropathy is originally microvascular in nature and is widely
      considered an important complication of diabetes. The present study was carried
      out to determine the efficacy of camel milk in controlling diabetic nephropathy.
      Twenty-four type-1 diabetic patients were randomly recruited from the outpatient
      diabetic clinic in PBM Hospital, Bikaner, India. All subjects gave their written
      consent before participation in the study. Patients with any acute metabolic
      complications were not included in the study. Eligible patients entered a run-in
      period of 1 month in which they were oriented to achieve the best possible
      glycemic control through standardized diet, standardized exercise regimen and
      insulin administration. During this period frequent monitoring of blood sugar was
      performed to maintain euglycemia. At the end of the run-in period, a base line
      evaluation was performed, then these patients were given camel milk in addition
      with usual care for six months. Urine microalbumin and blood sugar was measured
      twice a week before breakfast and dinner. There was a significant improvement in
      the microalbuminuria (119.48 +/- 1.68 to 22.52 +/- 2.68; p < 0.001) after
      receiving camel milk for 6 months. A significant reduction in the mean dose of
      insulin for obtaining glycemic control was achieved (41.61 +/- 3.08 to 28.32 +/-
      2.66; p < 0.01). This study was performed to observe the role of camel milk in
      controlling microalbuminuria levels in type-1 diabetic patients. It was observed
      that after adding camel milk to the usual regimen an improvement in
      microalbuminuria was reached (119.48 +/- 1.68 to 22.52 +/- 2.68; p < 0.001). This
      may be due to good glycemic control or to the direct effect of camel milk. The
      mechanism behind this effect is still unknown.

PMID- 19848051
TI  - Serum oxidative stress parameters of women with hypothyroidism.
AB  - In order to study the effects of hypothyroidism on parameters of oxidative stress
      in woman, we determined the values of thiobarbituric acid reactive substances
      (TBARS), Nitric Oxide (NO) and Paraoxonase (PON-1) using phenylacetate as
      substrates in serum. Women in fertile age were separated into three groups: a-
      euthyroidism (ET) control group, b- overt hypothyroidism (OHT) and c- subclinical
      hypothyroidism (SHT). TBARS concentration and the PON-1 activity as aryl esterase
      activity did not show differences between OHT, SHT and ET woman. The
      concentration of NO increased in OHT compared to ET. The SHT and ET NO values
      were not significantly different, but the NO level was higher in the serum of OHT
      compared to SHT. The OHT selectively increased the NO levels but did not modify
      the parameters of oxidative stress in the serum of fertile-age women.

PMID- 19848052
TI  - Gait analysis in patients undergoing ACL reconstruction according to Kenneth
      Jones' technique.
AB  - The anterior cruciate ligament is essential for knee stability, and its injury,
      both acute and in the case of chronic knee instability, promotes meniscal
      degenerative alterations, as well as the onset and progression of gonarthrosis.
      In this retrospective study, young adults engaged in nonprofessional sportive
      activities undergoing ACL reconstruction by the Kenneth-Jones technique were
      assessed clinically and with gait analysis, to detect any deficits persisting
      even after rehabilitation at a follow- up of approximately 6 months. Eight
      patients who had undergone elective ligament reconstruction by Kenneth-Jones were
      assessed between the 5th and 7th month postsurgery with clinical-anamnestic
      investigation, including the Hughston Clinic subjective knee questionnaire and by
      gait analysis with the EL.I.Te. system. Gait analysis showed a reduction of ACL
      protection mechanisms during initial stance; furthermore, the operated limb
      globally exhibited greater difficulty in muscle recruitment. Residual deficits in
      muscle recruitment, exposing the reconstructed ligament to possible injuries,
      persist after a rehabilitation program and after resuming ofpre-surgery
      activities, thus adjustment of the rehabilitative program on the basis of these
      findings is recommended.

PMID- 19848053
TI  - Aortic valve replacement with right thoracotomy in a patient with sternal
      metastasis from renal carcinoma.
AB  - We present a clinical case of severe aortic stenosis in a 73-year-old patient
      symptomatic for dispnoea class NYHA III-IV. At the physical examination the
      patient presented a single sternal metastasis of renal carcinoma involving the
      sternum. Oncological stability prompted us to perform aortic valve replacement.
      In order to avoid median sternotomy and its complications due to the presence of
      sternal metastasis we successfully performed aortic valve replacement through a
      right minithoracotomy.

PMID- 19848054
TI  - Superselective cannulation of coronary sinus branch with telescopic system during
      left ventricular lead placement.
AB  - We present a case of a 55-year-old man with idiopathic dilated cardiomyopathy,
      ejection fraction (EF) of 27%, left bundle branch block with QRS duration of 160
      ms, NYHA class III, and optimal medical therapy for at least 6 months who was
      referred to our division for cardiac resynchronization therapy (CRT) using a
      biventricular pacing device. During the operation, the coronary sinus branch
      cannulation failed using classical angioplasty guide wire techniques. The pacing
      lead was successfully implanted into the posterior target vein using a telescopic
      dual-catheter system.

PMID- 19848055
TI  - Quantum dot: magic nanoparticle for imaging, detection and targeting.
AB  - Quantum dots (QDs) are one of the nanoparticles that use in Imaging, Detection
      and Targeting. Quantum dots are nanometer-size luminescent semiconductor crystals
      and have unique chemical and physical properties due to their size and their
      highly compact structure. They emit different wavelengths over a broad range of
      the light spectrum from visible to infrared, depending on their size and chemical
      composi tion. Eventual use of quantum dots to dramatically improve clinical
      diagnostic tests for the early detection of cancer. The use of quantum dots
      heralds a revolution in biological imaging. The current and widely used organic
      fluorophores have two shortcomings associated with their fluorescence. Signals
      from the labeled molecules can be obscured by cell autofluorescence, occurring in
      the visible spectrum and by photobleaching which seriously limits observation
      time. Colloidal quantum dots are bright, photostable fluorophores of a few
      nanometers in diameter. Because their size approximates that of individual
      biomolecules, water-solubl quantum dot complex have been used to target and image
      tumor cells. Despite their advantages the best materials for quantum dots;
      cadmium sulfide, CdS and cadmium selenide, CdSe can be highly toxic. While
      enhancing the biocompatibility of this nanoparticle various encapsulation
      techniques have also aided in their water-dispersibility and functionalization.
      QDs were introduced to cell biology as alternative fluorescent probes in recent
      years. Traditional fluorophores, e.g. organic dyes and fluorescent proteins are
      limited by thei narrow absorption range, broad emission spectra and short
      fluorescent lifetime.

PMID- 19848056
TI  - A consensus document on the role of breakfast in the attainment and maintenance
      of health and wellness.

PMID- 19848057
TI  - The World Health Organization's surgical safety checklist.

PMID- 19848058
TI  - Laparoscopic subtotal cholecystectomy: initial experience with laparoscopic
      management of difficult cholecystitis.
AB  - AIM: Laparoscopic cholecystectomy (LC) is now accepted as the 'gold standard'
      procedure for cholecystectomy. However, a significant proportion of patients with
      complicated cholecystitis are still converted to 'open' to complete the
      procedure. Laparoscopic subtotal cholecystectomy (LSC) is an option, which is
      still too infrequently used. METHODS: A single surgeon in our NHS trust has
      performed 1150 LCs since September 1999. The procedure was converted to LSC in 52
      cases (4.52%) due to complicated cholecystitis. The data were collected and
      prospectively analysed for any morbidity or complications in the peri-operative
      period. RESULTS: At the initial presentation, 21 patients (40.38%) were diagnosed
      with recurrent biliary colic, 24 patients (46.15%) had acute cholecystitis, 6
      patients (11.53%) had jaundice, and 1 patient (1.92%) had peritonitis due to
      gallbladder (GB) perforation. Twenty-six cases (50%) were performed as
      emergencies, i.e. within one week of symptoms, and 26 (50%) were planned for
      surgery within four weeks after symptoms started. The cystic duct or Hartmann's
      pouch stump was closed using endo-loop application in 34 (65.38%), intracorporeal
      suturing of stump of Hartmann's pouch in 13 (25%), and closure of cystic duct
      opening in the Hartmann's pouch by purse-string suturing in 5 cases (9.62%).
      CONCLUSION: LSC is a safe option in treating gallstone disease when inflammation
      or fibrosis precludes conventional dissection of Calot's triangle. LSC can
      clearly help reduce morbidity associated with open laparotomy.

PMID- 19848059
TI  - What proportion of basic surgical trainees continue in a surgical career? A
      survey of the factors which are important in influencing career decisions.
AB  - INTRODUCTION: Since the launch of Modernising Medical Careers, trainees are
      selected for a run-through training programme in a single surgical specialty. The
      surgical training bodies are currently considering the recommendations of the
      Tooke report as they review the policy for selection into surgical training in
      the UK. There is little information available on the factors involved in career
      choices amongst surgical trainees and this study aimed to address this issue.
      METHOD: Trainees appointed to the Basic Surgical Training Programmes in the west
      and south-east of Scotland (1996-2006) were contacted by email and invited to
      participate in an online survey. RESULTS: Of 467 trainees identified, valid email
      addresses were available for 299 of which 191 (64%) responded to the survey. One
      hundred and forty-nine (78%) trainees were still working in surgery but 38 (20%)
      had moved to a non-surgical specialty and 4 (2%) had left the medical profession.
      Of those who had obtained a NTN at the time of the survey (n = 138), 62 (45%) had
      a NTN in the specialty they chose at the start of the BST but 34 (25%) had
      changed to a different surgical specialty and 42 (30%) had left surgery
      altogether. For those still working in surgery, enjoyment of the specialty was
      the most important factor affecting career choice. Achieving an acceptable
      work/life balance was the most significant factor influencing trainees who left
      surgery. CONCLUSION: The majority of trainees recruited to surgery at an early
      stage change specialty or leave surgery altogether. Both social and professional
      factors are important in career choices. The findings of this study support a
      period of core surgical training to provide flexibility prior to further training
      in a surgical specialty.

PMID- 19848060
TI  - Two week rule referral for patients with colorectal cancer below the age of 50;
      are we being ageist?
AB  - OBJECTIVES: The TWR system was introduced in July 2000. The purpose of this study
      was to investigate whether patients below the age of 50 years with colorectal
      cancer (CRC) are experiencing delays in treatment. METHODS: The CRC database was
      searched for all newly diagnosed colorectal cancers between January 2001 and
      December 2005 in patients who were aged less than 50 years. RESULTS: There were
      911 patients with CRC during the study period. Of these, 41 patients (4.5%) were
      aged under 50. Thirty-eight case notes were retrieved and reviewed; the median
      age was 47 years. Fourteen (37%) presented as an emergency, 9 (24%) via the TWR,
      8 (21%) were non-TWR referrals to outpatients and the remainder were referred via
      miscellaneous routes. The median time from referral to initial consultation was
      11 days (range 8-14 days) in the TWR group, 24 days (range 14-135 days) in the
      surgical outpatients group and 44 days (range 11-93 days) in the miscellaneous
      (direct endoscopy, in-hospital physician's referral) group. The median time from
      referral to initiation of treatment was 51 days (range 15-116 days) in the TWR
      group, 103 days (range 43-174 days) in the outpatient group and 96 days (range 27
      270 days) in the miscellaneous group. Excluding age as a factor, 73% of the non
      TWR referrals met the TWR criteria. CONCLUSION: Patients with symptoms of CRC
      below the age of 50 years may face referral and diagnostic delay if not referred
      via the TWR system; many of these would be eligible if age was not a deciding
      factor.

PMID- 19848061
TI  - Obesity management--an opportunity for cancer prevention.
AB  - There is increasing evidence of an association between obesity and the
      development, morbidity and mortality of cancers of the colorectum, (post
      menopausal) breast, endometrium, kidney, pancreas and oesophagus. In addition to
      obesity per se, waist circumference is now emerging as a clear indicator of
      disease risk. Weight gain during adult life also appears to increase risk for
      breast and colon cancers. Major causative factors which are influenced by excess
      energy storage include hormones involved in metabolic control (insulin and
      leptin), cell growth (IGF-I and IGF-binding proteins) and reproduction (steroids
      and leptin). In addition, raised oestrogens are likely to contribute to the
      greater risk of breast and endometrial cancers. In cancer survivors, there are
      also strong indications that being overweight increases the risk for recurrence
      and reduces the likelihood of survival. Whilst there are no robust data testing
      the effect of weight loss on recurrence, current guidance highlights that normal
      weight, overweight and obese patients should avoid weight gain and that a modest
      weight loss of 5-10% is likely to have significant health benefits. Two studies
      have now reported long-term effects of obesity surgery on cancer risk (in
      addition to reducing metabolic disorders and type 2 diabetes). It is becoming
      increasingly clear that multi-disciplinary groups (including surgeons) are needed
      to identify, monitor and evaluate programmes for both obesity prevention and
      management.

PMID- 19848062
TI  - Adequate surgery for papillary thyroid cancer.
AB  - Papillary thyroid cancer (PTC) is the most common type of thyroid cancer,
      occurring in about 80% of cases. Treatment consists ofsurgery, selective adjuvant
      radioiodine ablation, thyroid stimulating hormone suppression and surveillance.
      The extent of thyroidectomy and the extent of lymphadenectomy are controversial.
      Total or near-total thyroidectomy is recommended for the treatment of PTC, except
      those with papillary microcarcinoma (PTC < 1 cm) found incidentally after a
      thyroid lobectomy. This allows for treatment of possible multifocality (up to 8o%
      of cases), facilitates the use of radioiodine for remnant ablation and increases
      the sensitivity of thyroglobulin levels for surveillance, with complication rates
      comparable to lobectomy when done by experienced endocrine surgeons. A recent
      large database study supports this recommendation for PTCs > or = 1 cm; the
      optimal treatment of PTCs < 1 cm is still debatable, though many surgeons will
      perform total or near-total thyroidectomy for the reasons listed above.
      Contemporary series report lymph node metastases in up to 64% of patients, though
      their clinical significance is unclear. Reports are conflicting with respect to
      the impact of cervical nodal metastases on recurrence rates and survival, which
      are also affected by other patient, tumour and treatment-related factors.
      Therapeutic lymph node dissection is indicated for biopsy-proven nodal
      metastases. Prophylactic lateral neck lymphadenectomy is not recommended by
      experts in Europe and the USA. Prophylactic central neck lymphadenectomy is
      controversial, and may be advocated in selected patients while balancing the
      risks of the procedure.

PMID- 19848063
TI  - Graves' ophthalmopathy: the case for thyroid surgery.
AB  - Graves' disease is the most common cause of hyperthyroidism and is frequently
      complicated by ophthalmopathy, which can be a debilitating component of the
      disease, resulting in impaired quality of life. The management of Graves' disease
      aims to restore the patient to a euthyroid state and minimise the extent of
      extrathyroidal manifestations such as ophthalmopathy. Management options include
      medical therapy, radioactive iodine (RAI) and surgical intervention in the form
      of thyroid resection. Graves' ophthalmopathy (GO) is often resistant to or even
      aggravated by medical therapy and RAI, both of which have unpredictable relapse
      rates. The extent of thyroidectomy in the management of benign thyroid disease
      remains controversial. Total thyroidectomy is being increasingly favoured as the
      procedure of choice for treatment of benign thyroid disease. Recent study has
      indicated that it can be performed with minimal complications at a rate
      comparable to the less radical subtotal thyroidectomy. The predictable outcome
      and lack ofdisease recurrence make it an attractive option for benign conditions
      such as Graves' disease. In addition, there is increasing evidence that total
      thyroidectomy may have a beneficial effect, inducing an improvement in eye signs
      and symptoms in cases of GO. This review discusses the indications for surgical
      intervention in Graves' disease, with specific focus on the extent of resection
      and the relative merits of subtotal and total thyroidectomy in patients with GO.

PMID- 19848065
TI  - The role of the health services in the prevention of alcohol-related facial
      injury.
AB  - This paper outlines the preventive health strategic measures that are currently
      in place and it endeavours to consider how improvements can be made to our
      national preventive strategy with the goal of reducing alcohol-related facial
      injuries. It is based on a review of the literature sourced through PubMed, Ovid
      Medline and the Cochrane database. The main findings are that increased funding,
      legislative amendment and media involvement are key to improving the work of the
      health services in their struggle to limit the ever increasing alcohol-related
      incidents that are experienced by society today.

PMID- 19848064
TI  - High mobility group A: a novel biomarker and therapeutic target in pancreatic
      adenocarcinoma.
AB  - High mobility group A1 (HMGA1) proteins are architectural transcriptional factors
      that are over-expressed in a wide range of human malignancies. Recently published
      evidence suggests HMGA1 is a promising candidate biomarker and therapeutic target
      in pancreatic cancer. This review summarises data implicating HMGA1 as an
      important mediator of progression in human cancer and in pancreatic cancer.

PMID- 19848066
TI  - Vacuum assisted closure therapy in the treatment of mesh infection after hernia
      repair.
AB  - BACKGROUND: Mesh related infection after prosthetic abdominal wall hernia repair
      is a difficult clinical problem, particularly in an era of evolving microbial
      resistance. Commonly advocated treatment for such infection involves complete
      mesh excision which usually leaves a complicated weak wound. We report the use
      ofVAC therapy for mesh infections that allows mesh preservation leaving a sound
      wound. METHODS: From june 2002 to January 2007, four patients with mesh related
      infection after abdominal wall hernia repair were treated with VAC therapy.
      Patients' notes were reviewed to gather clinical details. RESULTS: Mesh infection
      was evident after a variable period (day three to eight years) following hernia
      repair. Of the four patients, one had infection with methicillin resistant
      Staphylococcus aureus (MRSA), while the bacteriological cultures from two
      confirmed Staphylococcus aureus in one and a mixture of Pseudomonas and
      enterococcus species in the other. One patient failed to show significant
      bacterial growth on pus swab culture, having had prior broad-spectrum antibiotic
      treatment for mesh infection. Three patients had complete mesh preservation and
      one had partial mesh excision. All patients were treated with VAC therapy,
      following the drainage of their operation sites, until the visible mesh was
      covered with granulation (one to seven weeks). No patient had a recurrent hernia
      after complete wound healing. CONCLUSION: VAC therapy allows salvage of infected
      exposed mesh by promoting granulation through the mesh. Judicious use of VAC
      therapy may prevent the need of mesh excision and its wound related
      complications.

PMID- 19848067
TI  - Re: A complication of intra-gastric balloon therapy.

PMID- 19848068
TI  - Molecular characterization of chicken infectious anemia virus circulating in
      Argentina during 2007.
AB  - Chicken infectious anemia virus (CAV) is a worldwide-distributed infectious agent
      that affects commercial poultry. Although this agent was first detected in
      Argentina in 1994, no further studies on CAV in this country were reported after
      that. The recent increased occurrence of clinical cases of immunosuppression that
      could be caused by CAV has prompted this study. Our results confirmed that CAV is
      still circulating in commercial flocks in Argentina. Phylogenetic analysis
      focusing on the VP1 nucleotide sequence showed that all Argentinean isolates
      grouped together in a cluster, sharing a high similarity (> 97%) with genotype B
      reference strains. However, Argentinean isolates were distantly related to other
      strains commonly used for vaccination in this country, such as Del-Ros and Cux-1.
      Sequence analysis of predicted VP1 peptides showed that most of the Argentinean
      isolates have a glutamine residue at positions 139 and 144, suggesting that these
      isolates might have a reduced spread in cell culture compared with Cux-1. In
      addition, a particular amino acid substitution at position 290 is present in all
      studied Argentinean isolates, as well as in several VP1 sequences from Malaysia,
      Australia, and Japan isolates. Our results indicate that it is possible to typify
      CAV strains by comparison of VPI nucleotide sequences alone because the same tree
      topology was obtained when using the whole genome sequence. The molecular
      analysis of native strains sheds light into the epidemiology of CAV in
      Argentinean flocks. In addition, this analysis could be considered in future
      control strategies focused not only on breeders but on broilers and layer flocks.

PMID- 19848069
TI  - Selection for increased nitric oxide production does not increase resistance to
      Marek's disease in a primary broiler breeder line.
AB  - Two primary broiler breeder lines, A and B, were examined for their potential to
      produce nitric oxide (NO) after stimulating splenocytes from 20-day-old embryos
      with lipopolysaccharide and interferon-gamma. Significant differences were found
      between lines A and B. Overall, line A had a higher response than line B, but
      line A also had a large degree of variation between individual sire families.
      Selection for high and low responders within line A resulted in the segregation
      of high- and low-responder sire families. Offspring from sire families selected
      for high and low NO responses and from a nonselected control group from line A
      were challenged with RB-1B Marek's disease (MD) virus to determine whether these
      differences could be used to select for improved resistance to MD. Virus
      isolation rates at 6 and 10 days postinfection were not significantly different,
      but unexpectedly, the MD incidence in the high-responder group was significantly
      higher than in the other two groups.

PMID- 19848070
TI  - Full genome sequences of two reticuloendotheliosis viruses contaminating
      commercial vaccines.
AB  - Reticuloendotheliosis virus (REV) fragments are a common contaminant in some
      commercial vaccines such as fowl poxvirus (FPV) and Marek's disease virus.
      However, only those strains integrating or containing a near-intact REV provirus
      are more likely to cause problems in the field. We confirm here, by PCR assays
      and animal experiments, that vaccines against FPV and herpes virus of turkeys
      were contaminated with full genome sequences of REV. Further, we determined the
      complete proviral sequence of two REV isolates from contaminated vaccines. Two
      REV isolates (REV-99 and REV-06) present in the vaccines were both replication
      competent, and their proviral genome was 8286 nucleotides in length with two
      identical long terminal repeats (LTR). The complete genome in these two REV
      isolates shared 99.8% identity to APC-566 and fowl poxvirus REV proviral inserts
      (FPV-REV). REV-99 and REV-06 LTR showed over 99% identity to chicken syncytial
      virus (CSV), but an identity of only 75.8% and 78.0%, respectively, to SNV.
      Alignments with other available REV gag, pol, and env sequences revealed high
      similarity at the nucleotide level. The results further indicated that the
      prototype CSV may be the most-important REV contaminant in the commercial
      vaccines, and distinct genotypes of REVs may cocirculate in chicken flocks of
      China at the present time.

PMID- 19848071
TI  - Identification and characterization of two distinct bursal B-cell subpopulations
      following infectious bursal disease virus infection of White Leghorn chickens.
AB  - Infectious bursal disease virus (IBDV) is an immunosuppressive virus which
      primarily infects IgM B-cells in the bursa of Fabricius. Flow cytometric analysis
      was used to phenotype B-cell populations in the bursa and spleen following IBDV
      infection. In the bursa, two IgM B-cell subpopulations, designated as A and B,
      were identified based on cell size and granularity. While both subpopulations
      differentially expressed IgM and Bu-1b surface markers, both groups displayed
      major histocompatibility complex class II surface antigens at equal levels.
      Following IBDV challenge of nonvaccinated birds, the B subpopulation was
      significantly reduced between 7 and 21 days postchallenge compared to either
      nonchallenged birds or vaccinated-challenged birds. However, the reduction of
      subpopulation B in the bursa, following IBDV exposure, did not reduce the levels
      of total serum IgA, IgG, and IgM, nor did it affect IgG and IgA B-cells in the
      spleen. Phenotypic analysis of the subpopulations identified differential
      expression of Lewis(x), IgM, Bu-1b, and MUI78 surface antigens between the
      subpopulations. Overall, these are the first studies to identify two distinct IgM
      B-cell subpopulations in the chicken bursa, and the first to describe the
      decrease in the IgM B-cell population relative to IgA and IgG B-cells following
      IBDV infection.

PMID- 19848072
TI  - Detection and molecular characterization of gene 3 and 5 of turkey coronavirus
      from turkeys with severe enteritis in Brazil.
AB  - Turkey coronavirus (TCoV) is a causative agent associated with poult enteritis
      and mortality syndrome (PEMS) in turkeys worldwide. The disease is an acute,
      highly contagious enteric disease that is characterized by depression, anorexia,
      diarrhea, and high mortality in commercial turkey flocks. The presence of TCoV in
      12 intestinal-content samples, from turkey flocks aged between 10 and 104 days
      and exhibiting severe enteritis, was monitored during the period of 2004 to 2006.
      TCoV detection was accomplished by a reverse transcriptase-polymerase chain
      reaction (RT-PCR) through amplification of the 3' UTR region, followed by
      amplification of genes 3 and 5. Molecular characterization of the viruses was
      done through amplification of genes 3 and 5 and showed evidence of genetic
      similarity between them, although they differed from sequences of other TCoVs
      described in the literature. In relation to gene 3, samples showed a greater
      relationship with chicken infectious bronchitis virus (IBV), while gene 5 showed
      greater identity with pheasant coronavirus (PhCoV). Our results suggest that the
      strategy of amplification of the 3' UTR region, followed by sequencing of genes 3
      and 5, has proven to be an effective means of detecting TCoV in intestinal
      contents.

PMID- 19848073
TI  - Identification and characterization of a duck enteritis virus US3-like gene.
AB  - Duck enteritis virus (DEV) causes substantial losses on duck farms; however, its
      molecular biology is poorly understood. Here, an open reading frame of a US3-like
      gene of DEV was identified from a DEV genomic library. Its existence was
      confirmed by cloning from DEV-infected duck embryo fibroblasts (DEFs) and DNA
      sequencing. The US3-like gene was then subcloned into a prokaryotic protein
      expression vector and expressed as a six-histidine-tagged fusion protein in
      Escherichia coli. The protein was purified and inoculated into rabbits for
      antiserum production. A primary antibody specific to the gene was successfully
      generated and used to detect the US3-like protein in DEV-infected duck cells. In
      vivo expression of the US3-like protein in DEV-infected DEFs was demonstrated
      with indirect immunofluorescence assay and regular fluorescence microscopy,
      whereas uninfected DEFs did not show any specific fluorescent staining.
      Furthermore, indirect immunofluorescence assay and confocal microscopy were used
      to study the time course and subcellular localization of the protein expression.
      The protein was found to be expressed as early as 2 hr postinfection, and its
      expression was increased by time at 4, 8, 12, and 24 hr postinfection. The
      protein was found to be localized mostly around the perinuclear area and in the
      cytosol, and also in the nucleus at later time points. In addition, a US3 protein
      phylogenetic tree was constructed and showed that the evolutionary relationship
      of DEV is close to the genus Mardivirus. In short, the DEV US3-like gene and its
      in vivo protein expression were found for the first time, and DEV classification
      and the gene's functions were suggested.

PMID- 19848074
TI  - Persistent infection of turkeys with an avirulent strain of turkey hemorrhagic
      enteritis virus.
AB  - The Virginia avirulent strain (VAS) of turkey hemorrhagic enteritis virus (THEV),
      which is commonly used in live vaccines for commercial turkeys, was studied to
      determine characteristics of infection. It has been observed that turkeys
      infected with the VAS maintain protective antibody levels in excess of 20 wk
      postvaccination. It is theorized that this immune response is modulated by either
      a persistent or latent infection. A series of studies have been undertaken to
      determine changes in virus location and serology over time. A trial was also
      conducted to evaluate the effect of corticosteroid administration on viral
      recrudescence, and an attempt was made to isolate live virus from tissues of
      birds 10 wk postinfection (pi). Antibody titers were determined by enzyme-linked
      immunosorbent assay, and PCR was used to detect viral DNA. Histopathology was
      performed on formalin-fixed paraffinized tissues. Viral DNA was detected in
      various tissues through 15 wk pi in the presence of high antibody titers. Viral
      DNA was detected at 3-5 days pi in the spleens of susceptible turkeys inoculated
      with tissues collected from infected birds at 10 wk pi. It is unknown whether the
      viral DNA is associated with live virus or rather is the result of persistent
      maintenance of the viral genome within lymphoid/macrophage target cells. Future
      studies will test for viral RNA in order to confirm the presence of replicating
      THEV. Regardless of the actual status of the THEV DNA detected at 10-15 wk pi, it
      is clear that THEV does not cause a simple acute infection. The characteristics
      of THEV infection are identical to the nonlytic persistent infections seen in
      human adenoviruses, and therefore THEV may serve as a model for the study of
      virus-cell interactions mediating persistence.

PMID- 19848075
TI  - Toward the development of a plant-based vaccine against reovirus.
AB  - Transgenic lines of Arabidopsis thaliana producing recombinant TC protein were
      developed. The S1 gene encoding sigmaC protein of an avian reovirus (ARV) was
      amplified by reverse-transcription PCR (RT-PCR). The amplified product was cloned
      into a plant-expression vector, pE1857, with a strong promoter for expression.
      The resulting construct with the BAR gene cassette for bialaphos selection was
      designated rpE-sigmaC and was introduced into Agrobacterium tumefaciens by
      electroporation. Agrobacterium containing the rpE-sigmaC constructs that
      transform A. thaliana and transgenic plants were selected using bialaphos
      selection. The presence of S1 transcript in plants and their relative level of
      expression were determined by real time RT-PCR. Western blot analysis further
      confirmed the presence of sigmaC protein in the plants. Transgenic lines with
      high levels of sigmaC protein were selected for immunization experiments using
      specific-pathogen free chickens. Recombinant sigmaC protein produced in plants
      induced a variety of immunoglobulin G (IgG) antibody responses in chickens.
      Recombinant protein administered either subcutaneously or orally in birds showed
      significant protection against challenge. Results suggested that the recombinant
      sigmaC protein produced in plants has the potential for large-scale vaccination
      against ARV in commercial poultry.

PMID- 19848076
TI  - Efficacy of autogenous killed vaccine of Avibacterium paragallinarum.
AB  - The efficacy of killed vaccine of Avibacterium paragallinarum with mineral oil
      adjuvant and aluminum hydroxide gel adjuvant was tested for antibody titers and
      protection. The autogenous vaccines at a concentration of 10(10) colony-forming
      units (CFU)/ml were administered to 5-wk-old male layers by subcutaneous
      injection in the neck twice at a 3-wk interval. Each chicken was challenged with
      10(8) CFU/ml in 400 microl of an homologous isolate of A. paragallinarum serotype
      A, IR1, at 4 wk after the second vaccination via the nasal route. Sera were
      collected and the antibodies were tested by the hemagglutination inhibition test.
      The results revealed that the autogenous mineral oil adjuvant vaccine provided
      the antibody titer significantly faster than the other groups (P < 0.05). The
      average antibody titers of the group vaccinated with autogenous mineral oil
      adjuvant vaccine were higher than those of the group vaccinated with autogenous
      aluminum hydroxide gel adjuvant vaccine. The protective ability of vaccines was
      assessed by infraorbital sinus swab after 5 days postchallenge. The autogenous
      vaccines prepared with mineral oil adjuvant and aluminum hydroxide gel adjuvant
      protected all the chickens after challenge. No bacteria were isolated from the
      infraorbital sinuses of chickens in either autogenous vaccine group with either
      high or low antibody titers. The commercial vaccines prepared from mineral oil or
      aluminum hydroxide gel adjuvant revealed some protection. This is in contrast to
      the unvaccinated control group, in which facial edema and serous nasal discharge
      was found, and bacteria could be isolated from all chickens in the group.

PMID- 19848077
TI  - Establishment of an aerosol-based Marek's disease virus infection model.
AB  - Marek's disease virus (MDV), which is the causative agent of Marek's disease
      (MD), is shed by infected chickens and transmitted to other chickens through the
      respiratory route. Experimental reproduction of MD has been commonly done either
      by intra-abdominal inoculation of cell-associated MDV or by exposure to MDV
      infected 'seeder' chickens. The former method does not mimic the natural route of
      MDV infection, whereas the latter method suffers from lack of uniformity in the
      timing and amount of virus transmission from seeder chickens to susceptible
      birds. The aim of the present study was to establish an infection model of MDV
      that mimics the natural route of infection. Here we report that when chickens
      were exposed for 20 min to aerosols (particle size 1.91 microm) of cell-free MDV
      suspensions containing 1280 plaque-forming units/ml, which were generated using a
      nebulizer, pathological and clinical signs of MD were observed in 95%-100% of the
      aerosol-exposed chickens by 21 days post-infection (dpi). Chickens that were
      exposed to aerosols and sampled at 1, 2, 3, 10, and 21 dpi showed MDV replication
      as early as 1 dpi in lungs as well as in other tissues such as spleen and bursa
      of Fabricius. This infection model will facilitate the studies directed to
      elucidate MDV-host interaction at the site of virus entry.

PMID- 19848078
TI  - Application of aluminum hydroxide for an in ovo live Newcastle disease vaccine.
AB  - Newcastle disease (ND) is a major threat to poultry, but the outbreak of the
      disease is well controlled by the vaccination. Recently, in ovo administration
      technology has been realized as a safe, efficacious, and convenient method for
      chicken vaccination. However, no in ovo administration has been applied for ND or
      other live vaccines that are highly pathogenic against chicken embryos. We found
      that an attenuated Newcastle disease virus (NDV) was applicable for an in ovo
      vaccination by adsorbing the virus to aluminum hydroxide (AH). Pathogenicity to
      chicken embryos of the AH-adsorbed NDV could be decreased compared with the
      administration of the virus alone. Namely, in ovo administration of the AH
      adsorbed attenuated NDV resulted in improved hatchability and survival rate and
      better antibody responses of protection-level immunity compared with the
      administration of NDV alone. However, further improvements in hatchability and
      survival rate are necessary for practical application. From these results, in ovo
      vaccination with the AH-adsorbed attenuated NDV was revealed to be safe and
      immunogenic to chicken embryos. The use of AH-adsorbed attenuated live viruses
      might be applicable for in ovo vaccinations against not only ND but also other
      avian infectious diseases.

PMID- 19848079
TI  - Induction of CXC chemokine messenger-RNA expression in chicken oviduct epithelial
      cells by Salmonella enterica serovar enteritidis via the type three secretion
      system-1.
AB  - The messenger-RNA (mRNA) expression of selected cytokines and chemokines in
      primary chicken oviduct epithelial cells (COEC) was determined following in vitro
      infections with wild-type or type three secretion system (T3SS)-mutant Salmonella
      enterica serovar Enteritidis (SE) strains. All SE strains examined in this study
      elicited the expression of proinflammatory immune mediators including inducible
      nitric oxide synthase (iNOS), CXCLi1 (K60), CXCLi2 (IL-8), CCLi3 (K203), and
      CCLi4 (MIP-1beta). SE also triggered the expression of an anti-inflammatory
      cytokine, IL-10, but repressed TGF-beta3 transcription. Both T3SS-1 (sipA and
      sipB) and T3SS-2 (pipB and ssaV) mutants showed reduced capacity, compared to the
      wild-type SE, to stimulate iNOS mRNA expression in COEC. T3SS-1 (sipA and sipB)
      mutants were significantly impaired in their ability to induce the expression of
      CXCLi1 and CXCLi2. T3SS-2 mutants displayed a wild-type phenotype in terms of
      modulating the expression of chemokines and cytokines in COEC. The expression of
      iNOS, but not CXC chemokines, correlated with the number of intracellular
      bacteria in COEC. Genetic complementation of the sipA mutation restored a wild
      type phenotype. Thus, SE induction of CXCLi1 and CXCLi2 was sipA-dependent. These
      results provide enhanced insights into the complex interplay between local host
      innate immune system and bacterial virulence factors.

PMID- 19848080
TI  - Sensitivity of isolates of Eimeria from turkey flocks to the anticoccidial drugs
      amprolium, clopidol, diclazuril, and monensin.
AB  - The sensitivity of field isolates of turkey coccidia from the United States to
      the anticoccidial drugs amprolium, clopidol, diclazuril, and monensin was
      investigated. Clopidol and diclazuril were the most effective, followed by
      monensin and amprolium. Thirty-one isolates were classified as resistant to
      amprolium, 23 resistant to monensin, 10 resistant to diclazuril, and 6 resistant
      to clopidol. Six isolates were partially resistant to monensin, 10 partially
      resistant to clopidol, and 11 partially resistant to diclazuril. Four isolates
      were sensitive to monensin, 12 sensitive to diclazuril, and 17 sensitive to
      clopidol.

PMID- 19848082
TI  - Effect of dosage and vaccination route on transmission of a live attenuated
      Mycoplasma gallisepticum vaccine: a broiler model.
AB  - Mycoplasma gallisepticum (MG) is an economically significant pathogen of poultry
      species. Among the table egg sector of the poultry industry, live attenuated
      strains of MG are commonly used to limit production losses associated with MG
      induced disease. These vaccines, however, may be problematic to broiler- and
      turkey-related industries because of associated virulence; therefore, an
      understanding of the transmissibility of the live MG vaccines is of particular
      importance. In the present study, a broiler model addresses the effect of vaccine
      application route and dosage on the transmission of the MG vaccine FVAX-MG to
      commingled unvaccinated subjects for 7 wk postvaccination. Vaccinations occurred
      at 2 wk of age via eyedrop or spray application at 1 x (4 x 10(6) colony-forming
      units [cfu]), 10(-3) x (4 x 10(3) cfu), or 10(-6) x (4 cfu) of the manufacturer's
      recommended dosage, and subsequent transmission to unvaccinated subjects was
      measured. The serologic response to MG antigen and the presence of MG DNA
      indicated FVAX-MG transmission only within the 1 x FVAX-MG eyedrop treatment.
      Among no other treatment was transmission of FVAX-MG detected. The results of the
      present study demonstrate that the dosage and vaccination route may have direct
      implications on subsequent transmission of FVAX-MG.

PMID- 19848081
TI  - Immunization of broiler chickens against Clostridium perfringens-induced necrotic
      enteritis using purified recombinant immunogenic proteins.
AB  - This study identified and assessed secreted proteins of Clostridium perfringens
      additional to those previously described for their ability to protect broiler
      chickens against necrotic enteritis (NE). Secreted proteins of virulent and
      avirulent C. perfringens were electrophoretically separated and reacted with
      serum of chickens immune to NE. Three immunoreactive protein bands unique to the
      virulent C. perfringens were identified by mass spectrometry as the toxin C.
      perfringens large cytotoxin (TpeL), endo-beta-N-acetylglucosaminidase (Naglu),
      and phosphoglyceromutase (Pgm). The genes encoding Naglu and Pgm proteins were
      cloned, and their gene products were purified as histidine-tagged recombinant
      proteins from Escherichia coli and used in immunizing chickens. Immunized and
      nonimmunized control broiler chickens were then challenged with two different
      strains (CP1, CP4) of C. perfringens and assessed for the development of NE. Of
      the two immunogens, Pgm immunization showed significant protection of broiler
      chickens against experimental NE, although protection reduced as challenge
      severity increased. However, birds immunized with Naglu were protected from
      challenge only with strain CP4. Birds immunized with these proteins had antigen
      specific antibodies when tested in an enzyme-linked immunosorbent assay. In
      conclusion, this study demonstrated the partial efficacy of additional secreted
      proteins in immunity of broiler chickens to NE. The study also showed that there
      may be differences in the protective ability of immunogens depending on the
      infecting C. perfringens strain.

PMID- 19848083
TI  - Cross-protection between West Nile and Japanese encephalitis viruses in red
      winged blackbirds (Agelaius phoeniceus).
AB  - Similar to West Nile virus (WNV), Japanese encephalitis virus (JEV) has a history
      of intercontinental spread, and birds are important for the maintenance and
      transmission of both of these closely related viruses. We examined viremic and
      serologic responses of blackbirds (Agelaius phoeniceus), with and without
      immunity to WNV, following experimental inoculation with two strains of JEV.
      Japanese encephalitis (JE) viremia was detected in only one of 16 (6.3%) WNV
      immune birds, while all 16 nonimmune birds had detectable JE viremia. Two weeks
      after JEV inoculation, all birds without pre-existing WNV immunity had clearly
      distinguishable anti-JEV antibodies, while in all birds with pre-existing WNV
      immunity, antibodies to WNV and JEV were either indistinguishable or the anti-WNV
      antibody titers were significantly higher. As WNV is endemic throughout much of
      North America, WNV immunity among birds may dampen transmission while
      complicating the serologic diagnosis of JEV, should this pathogen be introduced
      to North America.

PMID- 19848084
TI  - Characterization of new variants of avian infectious bronchitis virus in Tunisia.
AB  - Three infectious bronchitis virus (IBV) strains, isolated from suspected Tunisian
      broiler flocks, were characterized as variant viruses using genotyping and
      serotyping techniques. They were compared with commonly used vaccine strains,
      including 793/B, D274, and Massachusetts types. Reverse transcription-PCR
      restriction fragment length polymorphism, nucleotide sequencing, and GenBank
      BLAST database analyses of the hypervariable region of the S1 subunit of the
      virus spike gene showed that the three isolates, designated TN20/00, TN200/01,
      and TN335/01, share from 64% to 82% homologies between each other but are very
      different from the H120 strain, the only infectious bronchitis vaccine used in
      Tunisia. In addition, they showed from 57% to 78% similarities with the European
      genotypes, including D274 and 793/B. Phylogenetic data allowed classification of
      the three Tunisian isolates as new genotypes placed inside the same genetic group
      as the CR88121 and D274 genotypes but very distant from the Massachusetts
      genotype. Cross-virus neutralization tests confirmed the genotyping results and
      showed that both TN200/01 and TN335/01 isolates are serologically related,
      whereas the TN20/00 is closer to TN335/01 than to TN200/01. Moreover, all three
      Tunisian isolates are closely related to the European variant serotypes,
      including the CR88121 and the D274 strains, but none is serologically related to
      the H120 vaccine strain. These data demonstrated, for the first time in Tunisia,
      the cocirculation of IBV variant serotypes along with the Massachusetts type,
      causing severe clinical diseases and high economic losses to the poultry
      industry.

PMID- 19848085
TI  - Apoptosis induced by duck reovirus p10.8 protein in primary duck embryonated
      fibroblast and Vero E6 cells.
AB  - Muscovy duck reovirus (MDRV) is an important poultry pathogen that causes high
      morbidity and mortality in ducklings. The mechanisms by which viruses kill
      susceptible cells, and ultimately produce diseases, in Muscovy duck remain poorly
      understood. In this study, we focused on the biologic functions of the MDRV p10.8
      protein in vitro. The p10.8 protein is a small protein of MDRV that is encoded by
      the first open reading frame of the S4 segment. In our study, the p10.8-encoding
      gene was individually cloned and expressed in bacterial and eukaryotic cells. The
      p10.8 protein had no potential transmembrane domain; it shared no sequence
      similarity to other known fusion-associated small transmembrane proteins encoded
      by the avian reovirus, Nelson Bay virus or baboon reovirus; and it did not show
      any syncytium formation activity. The p10.8 protein induced apoptosis when
      expressed by itself in transfected primary Muscovy duck embryonic fibroblasts or
      in Vero E6 cells. Four assays were used to analyze the apoptosis induced by
      p10.8: DNA ladder formation; terminal deoxynucleotidyl transferase dUTP nick end
      labeling; enzyme-linked immunosorbent assay detection of cytoplasmic histone
      associated DNA fragments; and nuclear staining with propidium iodide. Two
      deletion products, p10.8delta1 (1-63aa; amino acid position) and p10.8delta2 (64
      96aa), were constructed. Deletion analysis suggests that p10.8delta1 (1-63aa) is
      important in mediating p10.8-induced apoptosis because its deletion abolishes
      induction of apoptosis.

PMID- 19848086
TI  - Evaluation of PCR and DNA sequencing for direct detection of Clostridium
      perfringens in the intestinal tract of broilers.
AB  - The aim of this investigation was to determine the presence of the opportunistic
      pathogen Clostridium perfringens by PCR and DNA sequencing, without previous
      cultivation. This methodology was then used to investigate how C. perfringens was
      affected by different preventive measures, such as ionophores and feed additives,
      for necrotic enteritis in broilers chickens. DNA was extracted from the
      intestinal content or intestinal tissue by DNA extraction kits. Detection limits
      for 16S rRNA, alpha-toxin, and cpb2 PCR gene targets were approximately 1 x
      10(3), 5 x 10(4), and 1 x 10(6) cells per g of intestinal content or tissue,
      respectively, as determined with samples spiked with C. perfringens. The method
      was evaluated with samples from single conventional broilers or from pools of six
      birds of experimentally reared broilers. Conventional chickens, raised with
      salinomycin in their feed, showed reduced numbers of C. perfringens-positive
      samples (P < 0.05) for all three PCR tests. With respect to cpb2, a tendency to
      detect more samples as positive for C. perfringens was observed with increasing
      age. The addition of sodium butyrate and lactic acid in the feed for experimental
      birds had a minor effect (P < 0.10) on positive samples, as detected with the 16S
      rRNA PCR. For experimental birds fed whole wheat, only three out of six pools of
      six birds allowed detection of C. perfringens by the 16S rRNA PCR, compared to
      five for the untreated controls or the Avilamycin- or prebiotic-treated birds.
      All 16S rRNA partial gene sequences obtained were identical and were 99.5%
      similar to the rrnB gene of the type strain of C. perfringens. Two types of the
      partial cpb2 gene sequence were detected with a similarity of 93%. One type was
      translated into protein, whereas a stop codon was found in the other type. Both
      types were located in the "atypical" phylogenetic group of the cpb2 gene
      sequences. The PCR test, based on extraction of DNA from intestinal content,
      provided rapid screening of poultry for C. perfringens without the need to have
      access to facilities in order to immediately cultivate and identify bacteria at
      the location of sampling. Further work is suggested to determine the relationship
      between the degree of necrotic enteritis, the actual level of C. perfringens in
      the animal, and the detection achieved by PCR.

PMID- 19848087
TI  - Molecular characterization of Brazilian infectious bursal disease virus isolated
      from 1997 to 2005.
AB  - This retrospective study concerned 41 infectious bursal disease virus (IBDV)
      isolates obtained from Brazilian broiler and layers flocks by reverse
      transcription-polymerase chain reaction. Twenty-five of them were identified as
      very virulent (vv) by restriction enzyme analysis and by further nucleotide and
      phylogenetic analysis. All of them had the typical amino acid residues, and all
      clustered in a phylogenetic tree with the vvIBDV strains. Four amino acid
      substitutions, at positions D213N, G254D, S317R, and D323E, were common to 3 vv
      isolates, Br/03/DB, Br/03/CK, and Br/04/CR, and differed from other vv isolates
      and strains. These isolates came from the same locale, but were collected in
      different years, indicating that the vvIBDVs circulating on Brazilian farms are
      undergoing slight but continuous exchanges.

PMID- 19848088
TI  - Serologic evidence of avian influenza (H4N6) exposure in a wild-caught raccoon.
AB  - Growing concerns about avian influenza, and its effect on agriculture and human
      health, have highlighted the need to understand the role of wildlife in
      maintaining and spreading the virus. We surveyed the wildlife inhabiting a
      poultry farm with recent H3N6 and H4N6 avian influenza virus exposure in
      Pennsylvania, U.S.A. One raccoon (Procyon lotor) tested positive for H4N6
      antibodies. This is the first recorded incident of avian influenza exposure in a
      wild raccoon. We suggest that raccoons may play a role in the transmission of
      avian influenza viruses and in compromising biosecurity efforts at poultry
      operations.

PMID- 19848089
TI  - Declining mortality in American crow (Corvus brachyrhynchos) following natural
      West Nile virus infection.
AB  - The American crow (Corvus brachyrhynchos) is known to suffer 100% mortality from
      infection with the New York 1999 strain of West Nile virus (WNV). Following the
      initial detection of WNV in North America in 1999, we measured prevalence of WNV
      reactive antibodies ("seroprevalence") in free-ranging American and fish crows
      (Corvus ossifragus) of central New Jersey after each transmission season through
      2005. In 2002, seroprevalence in American crow juveniles increased to 14% from
      the 5% of the previous year, potentially indicating increased survival in this
      species. Using the annual seroprevalence measurements and the number of human
      West Nile neuroinvasive disease cases as a surrogate for WNV transmission
      intensity, we developed a model to estimate the annual WNV-associated mortality
      rates among both of these crow species. Our model supports the hypothesis that
      mortality is changing over time; the WNV-associated mortality rate declined over
      time by 1.5% for American crow and by 1.1% for fish crow. The probability that
      the trend in mortality was negative was 90% for the American crow and 60% for the
      fish crow.

PMID- 19848090
TI  - Serotyping of Avibacterium paragallinarum isolates from Peru.
AB  - This study appears to represent the first serotyping study of 24 isolates of
      Avibacterium paragallinarum obtained from different regions of Peru during 1998
      2008. All isolates were characterized as beta-nicotinamide adenine dinucleotide
      dependent. According to the Page scheme, modified by Blackall, it was found that
      eight isolates were classified as serogroup A, seven isolates as serogroup B, and
      five isolates as serogroup C, while four isolates could not be serotyped. Further
      serotyping, following the same scheme but using rabbit antiserum raised against
      Argentinean strains of the three serogroups, allowed allocation of these four
      unclassified isolates to serogroup B. These results suggest that some of the
      Peruvian B isolates appear to be similar to the previously described variant B
      isolates from Argentina. Therefore, inactivated vaccines used in Peru should
      include the three recognized serogroups (A, B, and C), with the addition of at
      least one of these variant B isolates. Cross-protection trials are needed to
      compare the protection conferred by vaccines containing traditional B serovar
      strains to the protection by experimental vaccines containing variant B serovar
      isolates from Peru.

PMID- 19848091
TI  - Characterization of atherosclerosis by histochemical and immunohistochemical
      methods in African grey parrots (Psittacus erithacus) and Amazon parrots (Amazona
      spp.).
AB  - The aim of the study was to characterize atherosclerotic changes in African grey
      parrots (Psittacus erithacus) and Amazon parrots (Amazona spp.) by histochemical
      and immunohistochemical methods. Samples of the aorta ascendens and trunci
      brachiocephalici from 62 African grey parrots and 35 Amazon parrots were stained
      by hematoxylin and eosin and Elastica van Gieson for grading of atherosclerosis
      in these birds. Four different stages were differentiated. The incidence of
      atherosclerosis in the examined parrots was 91.9% in African grey parrots and
      91.4% in Amazon parrots. To evaluate the pathogenesis in birds,
      immunohistochemical methods were performed to demonstrate lymphocytes,
      macrophages, smooth muscle cells, and chondroitin sulfate. According to the
      missing lymphocytes and macrophages and the absence of invasion and proliferation
      of smooth muscle cells in each atherosclerotic stage, "response-to-injury
      hypothesis" seems inapplicable in parrots. Additionally, we found alterations of
      vitally important organs (heart, lungs) significantly correlated with
      atherosclerosis of the aorta ascendens.

PMID- 19848092
TI  - Atoxoplasmosis in canary fledglings: severe lymphocytic enteritis with
      preferential parasitism of B lymphocytes.
AB  - All fledgling canaries (Serinum canarius) in a small private aviary died from
      atoxoplasmosis during a single breeding season. The birds were clinically normal
      when removed from their parents at 2 mo of age, but by 3 mo of age all had died
      following an illness characterized by progressive lethargy, anorexia, and
      debilitation. Cachexia, splenomegaly, and pale foci in the liver were evident at
      necropsy. Microscopically, there was striking infiltration of the intestinal
      lamina propria by mononuclear cells that contained intracytoplasmic protozoa.
      Protozoa were also observed in mononuclear cells in splenic and hepatic sinusoids
      and in vascular or perivascular spaces of other organs, but were much less
      numerous. Ultrastructural features of infected enteric mononuclear cells were
      suggestive of lymphocytes, and the majority of parasitized cells in paraffin
      sections of intestine were positive for CD-79 antigen, consistent with B
      lymphocytes. CD-3 staining was minimal, suggesting little or no T-cell infection.
      The following year, after egg-laying was completed, adults were treated with
      sulfadimethoxine, and no further fledgling losses occurred.

PMID- 19848093
TI  - [Evaluation of the effectiveness of occupational safety and health inspections of
      construction sites in the Piedmont region from 2001 to 2005].
AB  - OBJECTIVES: To assess the effectiveness of safety inspections in the construction
      industry in Piedmont in terms of exposure to risk and injuries. METHODS: We
      conducted a retrospective analysis of the surveillance activities carried out in
      Piedmont between 2001 and 2005: to this purpose, we used a logical framework and
      we identified indicators to evaluate the process and its impact on exposure and
      injuries. RESULTS:  PROCESS: fixed standards involving the number of safety
      inspections and the type of constructions under control were respected; there was
      always sufficient diversity among the public works under control, although local
      health units used different working methods. Impact on exposure and injuries:
      injury rates in the construction industry in Piedmont showed a decreasing trend
      and systematically lower values compared to national rates. Injury rates in the
      "roads and railways" sector showed an increasing trend owing to the great number
      of public works under construction. In this case, the effect of preventive
      measures seems less noticeable, but this mainly depends on methodological limits,
      such as mismatch between numerator and denominator, difficulties in estimating
      the number of workers actually present on the sites, underreporting of minor
      events. CONCLUSIONS: Despite the limitations of a retrospective analysis, the
      Piedmont safety inspection programme for the construction industry showed
      coherence with the objectives and had a positive impact on injury rates.

PMID- 19848094
TI  - [A multidisciplinary preventive intervention in a large Italian hospital].
AB  - BACKGROUND: A multidisciplinary intervention is necessary to tackle the
      occupational risk of low back disorders in manual handling ofpatients and to
      evaluate the effectiveness. METHODS: An intervention was carried out which
      included risk assessment, testing and purchasing of patient handling devices,
      training programmes, health surveillance and collection of quantitative and
      qualitative outcomes to evaluate effectiveness, in a before-after design.
      RESULTS: The intervention was effective in reducing exposures, increasing
      knowledge and skills in patient-handling techniques, decreasing low back pain
      prevalence and injuries related to patient handling; absenteeism seemed to show a
      decreasing trend. CONCLUSIONS: The multidisciplinary approach was useful in the
      overall management of low back pain in health care workers performing patient
      handling.

PMID- 19848095
TI  - [Low back pain among video-terminal workers: ergonomic postural interventions].
AB  - BACKGROUND: Several studies report a high prevalence of low back pain (LBP) among
      video-terminal (VDT) workers. Targeted ergonomic interventions can help reduce
      the burden. OBJECTIVES: We investigated the long-term efficacy of an ergonomic
      postural intervention to address LBP among VDT workers. STUDY DESIGN: Non
      randomized, crossover trial. POPULATION AND SETTING: Four hundred employees
      working in the administrative offices of the two main buildings of the town hall
      ofForli who used VDTs for at least 20 hours a week; we randomly selected 100
      participants from each building. INTERVENTION: Ergonomic adjustment of the VDT
      workstation design. OUTCOME MEASURES: Changes in prevalence of LBP and work
      related posture. RESULTS: The ergonomic adjustment of the workstation improved
      work-related posture and reduced LBP in VDT operators who benefited from the
      intervention. CONCLUSIONS: A personalized ergonomic prevention intervention can
      improve work-related posture and LBP for VDT workers.

PMID- 19848096
TI  - [Noise-induced hearing loss: are health service surveillance programs always
      effective?].
AB  - OBJECTIVES: To evaluate noise-induced hearing loss in a group of workers at a
      steel engineering works over a 20 year period (1979-1999). METHODS: A total of
      2431 audiometric tests were performed in 708 workers (in 1979, 1984, 1989, 1994
      and 1999). Audiometric tests were classified so that hearing loss could be
      assessed over time. Additionally, personal noise exposure was measured for each
      worker (average, 85 dB(A) in tests carried out in 1992, 1996 and 1999). RESULTS:
      Over 5 years of noise exposure, mean cumulative incidence of noise-induced
      hearing loss was 8,2%. Over 10 years ofexposure (1979-89 or 1984-94 or 1989-99),
      the mean incidence was 15,3%. This percentage increased to 22,9% and 25,7% when
      the exposure lasted 15 or 20 years respectively. CONCLUSIONS: The considerable
      incidence of noise-induced hearing loss within the wide group of steel workers
      examined greatly exceeds the expected incidence related to the occupational
      exposure limits. The Evidence Based Occupational Medicine suggests that our
      health surveillance was not effective enough.

PMID- 19848097
TI  - [Experience of prevention activities in local health units. Assaults and
      musculoskeletal disorders].
AB  - BACKGROUND: Assaults against health care workers and musculoskeletal disorders
      are two significant issues for occupational health physicians. Training (the most
      common form of proposed intervention) by itself is not effective in reducing
      adverse effects. CASE REPORT: Two field studies are reported. The first
      experience targeted physical violence against nursing assistants in a long-term
      psychiatric care unit. The basic programme included architectural,
      organizational, educational, and clinical efforts and led to a significant
      reduction in aggressive behaviour by patients. The second experience, concerning
      prevention of musculoskeletal disorders in hospital workers, was based upon
      participatory ergonomic, educational, and rehabilitation measures. After the
      intervention, the prevalence of musculoskeletal symptoms decreased moderately,
      but significantly. Increased fitness for work was observed in workers.
      CONCLUSION: Multi-level and multi-purpose prevention programmes can be effective
      in reducing occupational health problems among health care workers.

PMID- 19848099
TI  - [Workplace health promotion interventions: ongoing projects and evaluation of
      their effectiveness].
AB  - BACKGROUND: The Italian law of January 2005 that banned smoking in enclosed
      public places, also banned smoking in the workplace. RESULTS: This law led to the
      elimination of exposure to passive smoking for non-smokers, more smokers who gave
      up smoking, and a fall in the number of cigarettes smoked per day among smokers.
      Enforcement of the ban needs to be strengthened in discotheques and at the
      workplace and in outdoor smoking premises. In covered outdoor areas set up for
      smokers in winter, passive smoking exposure is high. DISCUSSION: A Cochrane
      review conducted in 2005 on workplace smoking bans did not conclude that bans
      helped employees to quit, while another review found that totally smoke-free
      workplaces are associated with a 3.8% reduction in smoking prevalence, and 3.1
      fewer cigarettes smoked per person per day. CONCLUSIONS: Workplaces are ideal
      settings for health promotion, since it is feasible to organize individual
      interventions, such as counselling, combined with environmental measures (e.g.,
      smoking bans) in order to support behavioural changes in employees. It is
      difficult to evaluate these complex interventions using standard evaluation
      methods such as cluster randomized controlled trials. We describe two workplace
      interventions conducted in Tuscany based on methods described by Sorensen.

PMID- 19848100
TI  - [Workplace health promotion: evaluation of evidence of efficacy and
      methodological recommendations].
AB  - BACKGROUND: During the period 2004-2007 five Italian regions in cooperation with
      the Universities of Pavia and Perugia and the Italian Cochrane Centre carried out
      a research project on health promotion programmes. OBJECTIVES: Evaluation of
      efficacy of health education programmes developed by the Local Health Units from
      2000 to 2004. RESULTS: Analysis of 69 of health promotion programmes and 23
      Cochrane reviews led to establishing recommendations for health operators; at the
      workplace the efficacious actions were: to encourage consumption of healthy food
      (also via automatic distributors of fruit and vegetable snacks) and physical
      activity, guarantee observance of the smoking ban and/or offer assistance to quit
      smoking. CONCLUSION: Health promotion projects involve the use of public
      resources so it is necessary that the potential impact and efficacy be evaluated
      in the planning process. In particular, it is advisable to examine the data in
      the literature and assign preference to projects that have proved efficacious.

PMID- 19848098
TI  - [Feasibility of a screening programme for lung cancer among workers previously
      heavily exposed to asbestos].
AB  - BACKGROUND: We evaluated the feasibility and costs of a screening programme with
      spiral CT for the early diagnosis of lung cancer among workers previously heavily
      exposed to asbestos. METHODS: We invited 2000 workers, 1165 (58%) of whom
      accepted. Women and individuals with incomplete information were excluded; 1119
      subjects (mean age, 57 years) entered the main analysis. Subjects with non
      calcified lung nodules and/or dubious pleural plagues (No=338) entered a post
      screening diagnostic protocol based on radiological follow-up. RESULTS: Twenty
      five biopsies were performed (13 pulmonary, 9 pleural, 3 combined) revealed 5
      cases of lung cancer (including 1 in stage IA). The positive predictive value of
      the screening test was low (31%) despite its known high sensitivity (100%) and
      specificity (99%). Incidence of lung cancer was similar to that registered among
      male residents of the Veneto Region aged 55 to 59 years. The cost of the
      programme was Euro 1,000 per screened subject and Euro 245,000 per diagnosis
      (total cost, Euro 1,181,310). The total radiation dose administered to healthy
      subjects was about 1,100 mSv (220 mSv per lung cancer diagnosis). CONCLUSIONS:
      This screening programme was ineffective due to the low participation rate, the
      small number of diagnoses, low predictive value, and high costs.

PMID- 19848101
TI  - [Inequalities in protection and promotion of workers' health].
AB  - BACKGROUND: Occupational risks contribute to health inequalities, combined with
      psychosocial, behavioural, and environmental risk factors. Job Strain is a well
      known risk factor for cardio-vascular and psychiatric diseases. Furthermore,
      stressful conditions at work promote unhealthy life styles. Among workers, sex
      (female), young age and migration are all causes of health inequalities.
      CONCLUSIONS: Although evidence on the effectiveness of workplace interventions
      for addressing inequalities is limited, equity audits to support decisions need
      to be implemented in conjunction with workability and health promotion
      programmes, and simultaneously with measures of an environmental and social
      nature.

PMID- 19848102
TI  - [Role of a surveillance system developed by the Viareggio Local Health Unit in
      injury prevention].
AB  - BACKGROUND: Statistics on occupational injuries published by INVAIL (National
      Insurance Institute for Occupational Accidents and Diseases) are not useful to
      plan appropriate preventive actions in local manufacturing sectors. METHODS: The
      injury surveillance system, developed by Viareggio Local Health Unit, collects
      data on all occupational injuries that occurred in the Versilia area, by
      enterprise, worksite and manufacturing sector. Enterprises operating in
      particular sectors (e.g. shipyards, construction) are classified differently than
      in the national injury surveillance system. After trend analysis and
      interpretation of injury data, the main results are available both in electronic
      and paper format. RESULTS AND CONCLUSIONS: Surveillance data are used by the
      Local Health Unit to promote and formulate specific preventive actions, such as:
      research and development of safer tools, promotion and control of safer use of
      specific tools, promotion and enforcement of good practices, control programmes
      in high risk manufacturing sectors and jobs.

PMID- 19848103
TI  - [Workplace accident investigations carried out by local occupational health and
      safety units].
AB  - BACKGROUND: Workplace accident investigations place a heavy, time-consuming load
      on Italian Occupational Health and Safety Units of the National Health Service.
      Such investigations entail preventative measures, legal proceedings and likely
      penalties for enterprises. Staff shortages induce Units to reduce investigations
      in order to implement other preventive goals. METHODS AND RESULTS: This paper
      reports the actions that the Veneto Region performed to achieve a uni form
      treatment by all Units (inter-unit comparison and a new set of guidelines). We
      also describe a "short questionnaire-based investigation" aimed at encouraging
      enterprises to make preventive efforts, thereby enabling our staff to manage more
      events. CONCLUSIONS: We suggest and discuss effectiveness indicators for both
      practices.

PMID- 19848104
TI  - [A simplified occupational health and safety management system designed for small
      enterprises. Initial validation results].
AB  - BACKGROUND: Occupational Health and Safety Management Systems (OHSMS) are known
      to be effective in improving safety at work. Unfortunately they are often too
      resource-heavy for small businesses. OBJECTIVES: The aim of this project was to
      develop and test a simplified model of OHSMS suitable for small enterprises.
      METHODS: The model consists of 7 procedures and various operating forms and check
      lists, that guide the enterprise in managing safety at work. The model was tested
      in 15 volunteer enterprises. RESULTS: In most of the enterprises two audits
      showed increased awareness and participation of workers; better definition and
      formalisation of respon sibilities in 8 firms; election of Union Safety
      Representatives in over one quarter of the enterprises; improvement of safety
      equipment. The study also helped identify areas where the model could be improved
      by simplification of unnecessarily complex and redundant procedures.

PMID- 19848105
TI  - [Tuberculosis risk assessment in Italian healthcare centres].
AB  - BACKGROUND: Tuberculosis transmission is a significant hazard in healthcare
      settings. METHODS: Risk factors suggested by CDC guidelines in 1994, which were
      adopted by the Italian Ministry of Health, were assessed in 29 centres via
      questionnaires in 2005. RESULTS: Few centers were equipped with negative
      pressure, respiratory isolation rooms. Half of the centres had high or ongoing
      risk. CONCLUSIONS: The hazard is underestimated mostly because of a high number
      of initially undiagnosed TB patients.

PMID- 19848106
TI  - [Effectiveness of preventive measures for workplace health and safety in
      Lombardia region during the period 2007-2008].
AB  - BACKGROUND: The Lombardy Region has managed workplace safety prevention projects
      via evaluation of efficacy indicators since 1998 but is only now measuring the
      effectiveness of heir application. For the 3-year period 2008-2010 Regional Law
      8/2007 made it mandatory for all injury prevention departments to assess
      effectiveness. A study carried out by the International Labour Organization
      concluded that investigations carried out to identify the causes and the
      responsibilities of work accidents or occupational diseases are extremely
      effective in improving the sureveillance and prevention system. METHODS: The
      ratio between the number of cases in which it was possible to identify an
      individual who could be charged with penal responsibilities and the number of
      investigated cases were taken as an efficacy indicator ofHealth Service
      investigation procedures. RESULTS AND DISCUSSION: Analysis revealed that in only
      29% of the 5008 industrial injuries, investigated and in 16% of the 2370
      occupational diseases assessed was it possible to identify penal
      responsibilities. These percentages appear too low and a revision of the
      investigation protocol is therefore necessary mainly as regards priority criteria
      for the selection of cases to be investigated.

PMID- 19848107
TI  - Thomas Eakins and his medical clinics.

PMID- 19848108
TI  - Moving android: on social robots and body-in-interaction.
AB  - Social robotics studies embodied technologies designed for social interaction.
      This paper examines the implied idea of embodiment using as data a sequence in
      which practitioners of social robotics are involved in designing a robot's
      movement. The moments of learning and work in the laboratory enact the social
      body as material, dynamic, and multiparty: the body-in-interaction. In describing
      subject-object reconfigurations, the paper explores how the well-known ideas of
      extending the body with instruments can be applied to a technology designed to
      function as our surrogate.

PMID- 19848109
TI  - Drug evaluation and the permissive principle: continuities and contradictions
      between standards and practices in antidepressant regulation.
AB  - Pharmaceuticals are not permitted on to the market unless they are granted
      regulatory approval. The regulatory process is, therefore, crucial in whether or
      not a drug is widely prescribed. Regulatory agencies have developed standards of
      performance that pharmaceuticals are supposed to meet before entering the market.
      Regulation of technologies is often discussed by reference to the precautionary
      principle. In contrast, this paper develops the concept of the 'permissive
      principle' as a way of understanding the departure of regulators' practices from
      standards of drug efficacy to which regulatory agencies themselves subscribe. By
      taking a case study of antidepressant regulation in the UK and the USA, the
      mechanisms of permissive regulatory practices are examined. An STS methodology of
      both spatial (international) and temporal comparisons of regulatory practices
      with regulatory standards is employed to identify the nature and extent of the
      permissive regulation. It is found that the permissive principle was adopted by
      drug regulators in the UK and the USA, but more so by the former than the latter.
      Evidently, permissive regulation, which favours the commercial interests of the
      drug manufacturer, but is contrary to the interests of patients, may penetrate to
      the heart of regulatory science. On the other hand, permissive regulation of
      specific drugs should not be regarded as an inevitable result of marketing
      strategies and concomitant networks deployed by powerful pharmaceutical
      companies, because the extent of permissive regulation may vary according to the
      intra-institutional normative commitments of regulators to uphold their technical
      standards against the commercial interests of the manufacturer. Likely
      sociological factors that can account for such permissive regulatory practices
      are 'corporate bias', secrecy and excessive regulatory trust in the
      pharmaceutical industry in the UK, political expediency and ideological capture
      in the USA, combined in both countries with some regulatory deference to the
      clinical autonomy of the psychiatry profession.

PMID- 19848110
TI  - Active compounds and atoms of society: plants, bodies, minds and cultures in the
      work of Kenyan ethnobotanical knowledge.
AB  - This paper examines a sequence of investigations in parasitology, botany,
      pharmacology, psychometrics and ethnopsychology focused on Kenyan village
      children's knowledge of medicinal herbs. We follow this work of making and
      ordering of knowledge, showing that the different disciplinary perspectives on
      bodies, medicines, knowledges, children and cultures produced by this research
      all sought the foundation of knowledge in reference to objective reality, and
      that they aimed to make the world known in the specific form of distinct and
      comparable entities with individual properties and capacities. Based on
      subsequent ethnographic observations of healing in the same village, we outline a
      different, contrasting modality of knowing, which places ontology above
      epistemology. Medicinal knowledge and its transformational capacity are here not
      located within entities but between them; not in objective reality but in
      effects; 'to know' means 'to come together' with the implication of having an
      effect on one another. We use this ethnographic sketch of a different form of
      knowing as a foil against which to contrast the imaginary that had shaped our
      previous research. Beyond the stark contrast between herbal village healing and
      pharmacological laboratory analysis, we expand our argument by moving from
      natural science to social science, from studies of plants and substances to those
      of humans, minds and cultures; from laboratories to ethno-psychological tests,
      cultural models, and eventually econometrics. We suggest that by reiterating a
      particular scientific imaginary, remaking humans (and non-human beings) as known
      things, a specific notion of man and a related political economy of knowledge is
      naturalized. Looking back at our involvement with this sequence of research, we
      realize that, contrary to our intentions, our inclusion as 'social scientists'
      into a multidisciplinary scientific project may have exacerbated rather than
      mitigated its potentially problematic effects.

PMID- 19848111
TI  - "The physician's hand": trends in the evolution of the apothecary and his art
      across Europe (1500-1700).
AB  - This article surveys the place of the apothecary in the Italian and wider
      European social and professional context of the sixteenth and seventeenth
      centuries. In contrast to localized studies, a comparison across Europe can serve
      to measure the general pace and lines of development. The type of goods the
      apothecary sold will be analyzed, as well as the professional evolution of the
      apothecary and the competition offered by rival groups. Here, the apothecary
      shall be placed somewhere between merchants and medics, but his relationship with
      the civic authorities and the traditional guild structure shall also be
      elucidated. We shall see how changing circumstances, economic shifts and new
      therapeutic technologies affected the apothecary and his place in the world. For
      the Italian apothecary, trends only pointed to his eclipse, as northern European
      pharmaceutical texts, manufacture of medicinal goods and precepts of "the new
      science" came to the fore.

PMID- 19848112
TI  - The dispensary movement, apothecaries and the supply of medicines 1696 to 1949.

PMID- 19848113
TI  - A tribute to Jacques Buffle: founding father of dynamic metal speciation
      analysis.

PMID- 19848114
TI  - Discontinued pajama flame retardant detected in baby products and house dust.

PMID- 19848115
TI  - Algae: fuel of the future?

PMID- 19848116
TI  - Peruvian gold rush threatens health and the environment.

PMID- 19848117
TI  - Jacques Buffle: complex insight and environmental solutions.

PMID- 19848118
TI  - Chemodynamics and bioavailability in natural waters.

PMID- 19848119
TI  - Chemodynamics of aquatic metal complexes: from small ligands to colloids.
AB  - Recent progress in understanding the formation/dissociation kinetics of aquatic
      metal complexes with complexants in different size ranges is evaluated and put in
      perspective, with suggestions for further studies. The elementary steps in the
      Eigen mechanism, i.e., diffusion and dehydration of the metal ion, are reviewed
      and further developed. The (de)protonation of both the ligand and the
      coordinating metal ion is reconsidered in terms of the consequences for
      dehydration rates and stabilities of the various outer-sphere complexes. In the
      nanoparticulate size range, special attention is given to the case of fulvic
      ligands, for which the impact of electrostatic interactions is especially large.
      In complexation with colloidal ligands (hard, soft, and combination thereof) the
      diffusive transport of metal ions is generally a slower step than in the case of
      complexation with small ligands in a homogeneous solution. The ensuing
      consequences for the chemodynamics of colloidal complexes are discussed in detail
      and placed in a generic framework, encompassing the complete range of ligand
      sizes.

PMID- 19848120
TI  - Effective affinity distribution for the binding of metal ions to a generic fulvic
      acid in natural waters.
AB  - The effective distribution of affinities (Conditional Affinity Spectrum, CAS)
      seen by a metal ion binding to a humic substance under natural water conditions
      is derived and discussed within the NICA-Donnan model. Analytical expressions for
      the average affinity of these distributions in general multi-ion mixtures are
      reported here for the first time. These expressions enable a simple evaluation of
      the effect of all interfering cations on the affinity distribution of a given
      one. We illustrate this methodology by plotting the affinity spectra of a generic
      fulvic acid for 14 different cations in the presence of major inorganic ions and
      trace metals at pH and concentration values representative of a river water. The
      distribution of occupied sites and their average affinity at the typical
      freshwater conditions are also reported for each ion. The CAS allows usto
      distinguish three groups of cations: (a) Al, H, Pb, Hg, and Cr, which are
      preferentially bound to the phenolic sites of the fulvic ligand; (b) Ca, Mg, Cd,
      Fe(II), and Mn, which display a greater effective affinity for carboxylic sites,
      in contrast to what would be expected from their individual complexation
      parameters; and (c) Fe(III), Cu, Zn, and Ni, for which phenolic and carboxylic
      distributions are overlapped.

PMID- 19848121
TI  - Metal complexation by humic substances in seawater.
AB  - We determined the complex stability of copper, zinc, cobalt and aluminum with
      humic acid (HA) and fulvic acid (FA) in pH 8 seawater. The method is based on
      metal competition against iron, for which the complex stability with humic
      substances (HS) in seawater had been calibrated previously against EDTA. The
      conditional stability constants, log K'(Mn+HS) values, were found to decrease in
      the order of Cu > Zn > Co and Fe > Al. The complex stability of the HA species
      was greater than the FA species, but all determined complex stabilities are
      sufficiently high for significant complexation of the examined metals by HS in
      seawater. Data modeling shows a good data fit over the entire titrations for Cu
      and Co and for low levels of Zn. A second site on the HS appears to bind higher
      levels of Zn. The Al data suggest that Fe is exchanged for Al at a ratio
      different from 1:1. The data suggests that HS may be an important ligand for
      these metals in seawater.

PMID- 19848122
TI  - Effects of fulvic and humic acids on arsenate adsorption to goethite: experiments
      and modeling.
AB  - Data for interactions between arsenate (AsO4(3-) and fulvic acids (FA) or humic
      acids (HA) at the surface of goethite are presented (pH 3-7, ionic strength 2 mM
      and 10 mM). Adsorption of FA and HA leads to desorption of arsenate and a
      correspondingly strong increase of arsenic concentration in solution. Adsorption
      of both FA and HA is mutually decreased by the competition with arsenate. The
      competition between FA and arsenate is much stronger than that between HA and
      arsenate. Using an advanced model, the LCD model (Ligand and Charge
      Distribution), arsenate adsorption to goethite in the presence of both adsorbed
      FA and HA can be predicted reasonably well. The stronger effects of FA on
      arsenate adsorption are caused, according to the model, by its spatial location
      which is closer to the oxide surface, and as a consequence, the electrostatic
      interactions between adsorbed FA particles and arsenate ions are much stronger
      than those for HA particles. The results show that site and electrostatic
      competition are the major mechanisms explaining the effects of natural organic
      matter on the arsenic speciation, whereas other possible mechanisms, such as a
      chemical reduction of arsenate to arsenite and formation of ternary organic
      arsenic complexes, are of minor significance.

PMID- 19848123
TI  - Sorption to humic acids enhances polycyclic aromatic hydrocarbon biodegradation.
AB  - The hypothesis that humic acids (HA) can act as carriers of polycyclic aromatic
      hydrocarbon (PAH) compounds and provide bacteria with PAH fluxes beyond those
      obtained by diffusion of the water-dissolved fraction of these poorly soluble
      chemicals was tested. Controlled degradation experiments using microcrystalline
      phenanthrene and Sphingomonas sp. LH162 were performed without HA and in the
      presence of two HA concentrations. In the absence of HA, phenanthrene was
      steadily present at the maximum dissolved concentration, indicating that the
      phenanthrene dissolution flux compensated for the consumption. This was confirmed
      by dissolution experiments where phenanthrene dissolved roughly an order of
      magnitude faster than it was consumed in the degradation experiments.
      Interestingly, the presence of HA further increased the rates of phenanthrene
      degradation by factors up to 4.8 in an HA concentration-dependent manner. This
      can only be interpreted by an HA-mediated transport of phenanthrene to the cells,
      supplementing diffusive uptake from the freely dissolved phase. It is proposed
      that HA-sorbed phenanthrene is released directly to the cells upon their
      interaction with HA aggregates, increasing the total phenanthrene flux and also
      degradation.

PMID- 19848124
TI  - Dissolved organic matter enhances transport of PAHs to aquatic organisms.
AB  - In this study, the uptake of pyrene and benzo[b]fluoranthene by an aquatic worm
      (Lumbriculus variegatus) and a poly(dimethylsiloxane) coated glass fiber was
      studied at different humic acid concentrations. The accumulation of pyrene was
      not affected by the presence of the humic matrix. However, the accumulation rate
      of benzo[b]fluoranthene increased a factor of 3 for the fiber and a factor of 4
      when 55 mg L(-1) dissolved organic carbon was added in the form of humic acid.
      The difference between the two chemicals can be explained by the higher affinity
      of benzo[b]fluoranthene for the dissolved humic material. A comparison of modeled
      transport enhancement of benzo[b]fluoranthene by humic acid and the experimental
      results suggested that the benzo[b]fluoranthene complexed with the humic phase
      was not completely labile.

PMID- 19848126
TI  - Multimetal interactions between Cd, Cu, Ni, Pb, and Zn uptake from water in the
      zebrafish Danio rerio.
AB  - The uptake of essential (Cu, Ni, and Zn) and nonessential (Cd and Pb) metals in
      the gills and whole body of zebrafish exposed to a mixture of trace elements at
      environmentally relevant concentrations was investigated using a stable isotope
      technique. Negative and positive interactions as well as nonlinear responses were
      observed. The Cd and Pb uptake processes were influenced the most by other
      metals. The uptake of Cd was inhibited by Cu, Pb, and Zn and enhanced in the
      presence of Ni at concentrations above 0.1 microM. Pb uptake rates were
      consistently increasing in the presence of Cd, Ni, and Zn in both gills and the
      whole body, except in one case of decreased whole body Pb uptake in the presence
      of Cd. The addition of Cu resulted in more complex nonlinear variations in Pb
      uptake rates. The addition of Pb, in turn, facilitated Cu uptake with a more
      pronounced effect in the gills, while Zn had a stimulating effect on the whole
      body level. Uptake of Ni continuously decreased with the addition of Zn, and some
      decline in whole body Ni accumulation was observed in the presence of Cd. In
      contrast Cu increased the Ni uptake rates in both gills and the whole body. The
      results demonstrate the complexity of the uptake processes occurring in media
      containing a mixture of metals at environmentally relevant concentrations. These
      interactions may be of key significance in understanding and predicting metal
      uptake, accumulation, and toxicity in multimetal exposure scenarios.

PMID- 19848125
TI  - Role of the siderophore azotobactin in the bacterial acquisition of nitrogenase
      metal cofactors.
AB  - Fixation of dinitrogen by soil bacteria is catalyzed by the enzyme nitrogenase
      which requires iron, molybdenum, and/or vanadium as metal cofactors. Under
      conditions of iron deficiency, the ubiquitous N2-fixing bacterium Azotobacter
      vinelandii produces azotobactin, a fluorescent pyoverdine-like compound which
      serves as a siderophore. Azotobatin's hydroxamate, catechol, and alpha-hydroxy
      acid moieties endow it with a very high affinity for Fe(III), and the Fe complex
      is taken up by the bacterium. Here we show that azotobactin also serves for the
      uptake of Mo and V. Azotobactin forms strong complexes with molybdate and
      vanadate and the complexes are taken up by regulated transport systems. The
      kinetics of complexation of molybdate and vanadate by azotobactin are faster than
      the complexation of Fe(III), which is either precipitated or bound to strong
      complexing agents. As a result of this kinetic advantage, the Mo and V complexes
      of azotobactin form despite the higher affinity of the compound for Fe, which is
      present in large excess in the environment. The results obtained here for
      azotobactin and previous data for the bis- and tris-catechols produced by A.
      vinelandii show that those "siderophores" are really "metallophores" that promote
      the bacterial acquisition of Mo and V in addition to Fe.

PMID- 19848127
TI  - In situ speciation measurements of trace metals in headwater streams.
AB  - Concentrations of Al, Fe, Mn, Ni, Cu, Cd, Pb, and Zn were measured using DGT
      (diffusive gradients in thin-films) devices deployed in situ in 34 headwater
      streams in Northern England. Mean values of filtered samples analyzed by ICP-MS
      (inductively coupled plasma mass spectrometry) were used, along with DOC
      (dissolved organic carbon), pH and major ions, to calculate the distribution of
      metal species using the speciation code WHAM. DGT-measured concentrations,
      [Me]DGT, of Zn and Cd were generally similar to concentrations in filtered
      samples, [Me]filt. For the other metals, [Me]DGT was similar to or lower than
      [Me]filt. Calculation of the maximum dynamic metal from the speciation predicted
      using WHAM showed that most of the lower values of [Cu]DGT could be attributed to
      the dominance of Cu-fulvic acid complexes, which diffuse more slowly than simple
      inorganic species. Similar calculations for Al, Pb, and Mn were consistent with
      appreciable proportions of these metals being present as colloids that are not
      simple complexes with humic substances. Differences between WHAM predictions and
      the measured [Ni]DGT indicated that WHAM used with the default binding parameters
      underestimates Ni binding to natural organic matter. Plots of [Me]DGT versus the
      ratio of bound metal to DOC provided slight evidence of heterogeneous binding of
      Pb and Cu, while results for Mn, Cd, and Zn were consistent with weak binding and
      complete lability.

PMID- 19848128
TI  - In situ monitoring of the diurnal cycling of dynamic metal species in a stream
      under contrasting photobenthic biofilm activity and hydrological conditions.
AB  - The diurnal evolution of the dynamic fraction, i.e., the potentially bioavailable
      fraction, of Cd, Cu, and Pb in a small river impacted by mining and smelting
      waste was studied in situ, under contrasting biofilm activity and hydrological
      conditions, using an automated voltammetric analyzer. The in situ, near real-time
      measurements revealed persistent dynamic metal species diurnal cycles. These
      cycles were affected mainly by the biochemical conditions rather than
      hydrological conditions. The data obtained from the in situ measurements, coupled
      with complementary laboratory analyses, revealed that various processes control
      the diurnal dynamic metal species cycles in the studied site; the trends of the
      diurnal cycles of the dynamic metal species can be different from those observed
      for the dissolved metal species measured in filtered samples. Moreover, the
      dynamic fraction of a given cationic metal can show diurnal cycles with opposite
      trends depending on the environmental conditions. All these findings highlight
      the interest and importance of automated, continuous measurements of specific
      relevant environmental metal fractions, compared to punctual weekly or monthly
      traditional sampling strategies of total dissolved metal analysis, to allow more
      appropriate water quality control and reliable assessment of metal
      ecotoxicological impact.

PMID- 19848129
TI  - Phototrophic biofilm activity and dynamics of diurnal Cd cycling in a freshwater
      stream.
AB  - Diel cycles of dissolved cationic metal concentrations commonly occur in
      freshwater streams in apparent response to coincident cycles in water quality
      parameters (pH, O2, temperature). Hourly sampling of the Cd-contaminated Riou
      Mort (France) revealed large diel cycles in "total" dissolved Cd (232-357 nM; <
      0.45 microm) and "truly" dissolved Cd (56-297 nM; < 0.02 microm) which were
      strongly correlated with changes in water pH. Using measured fluxes, a dissolved
      O2 model was constructed that indicated that benthic metabolic activities,
      respiration and photosynthesis, were responsible for the diel O2 (and thus, CO2
      and pH) variation in the stream. However, microsensor measurements also showed
      that the pH changes occurred at the biofilm interface earlier than in the bulk
      water column. This difference in timing was reflected in the Cd dynamics, where
      pH-controlled sorption effects caused Cd partitioning from the truly dissolved
      pool onto the biofilm in the morning, and from the truly dissolved pool onto
      large colloids (0.02-0.45 microm) later in the day. Because this process causes
      large changes in the bioavailable Cd fraction, it has significant implications
      for Cd toxicity in freshwater streams. This study demonstrates the profound
      control of benthic microbiological processes on the cycling of heavy metals in
      aquatic systems.

PMID- 19848130
TI  - Zero-valent sulfur and metal speciation in sediment porewaters of freshwater
      lakes.
AB  - We measured the aqueous solubility of rhombic sulfur and used this information to
      incorporate, in speciation codes, the thermodynamic constants reported in the
      literature for the formation of polysulfide complexes. Using the values of pH and
      total concentrations of dissolved zerovalent sulfur, sulfide, humic substances,
      trace metals (Ag, Cd, Cu, Hg, methylmercury, Pb, Zn) and major ions measured in
      anoxic porewaters of nine oligotrophic Canadian lakes as input to these
      speciation codes, we show that the porewaters of these lakes are undersaturated
      or close to saturation with respect to rhombic sulfur and that sulfide and
      polysulfide ligands play a dominant role in controlling metal speciation in
      freshwater anoxic environments when they are present at micromolar levels. The
      study also highlights the need for further research on the formation constants of
      metal complexes with sulfide and polysulfides.

PMID- 19848131
TI  - Organo-iodine formation in soils and aquifer sediments at ambient concentrations.
AB  - One of the key risk drivers at radioactive waste disposal facilities is
      radioiodine, especially 129I. As iodine mobility varies greatly with iodine
      speciation, experiments with 129I-contaminated aquifer sediments from the
      Savannah River Site located in Aiken, SC, were carried out to test iodine
      interactions with soils and aquifer sediments. Using tracer 125I- and stable 127I
      additions, it was shown that such interactions were highly dependent on I-
      concentrations added to sediment suspensions, contact time with the sediment, and
      organic carbon (OC) content, resulting in an empirical particle-water partition
      coefficient (Kd) that was an inverse power function of the added I-
      concentration. However, Kd values of organically bound 127I were 3 orders of
      magnitude higher than those determined after 1-2 weeks of tracer equilibration,
      approaching those of OC. Under ambient conditions, organo-iodine (OI) was a major
      fraction (67%) of the total iodine in the dissolved phase and by implication of
      the particulate phase. As the total concentration of amended I- increased, the
      fraction of detectable dissolved OI decreased. This trend, attributed to OC
      becoming the limiting factor in the aquifer sediment explains why at elevated I
      concentrations OI is often not detected.

PMID- 19848132
TI  - Modeling the adsorption and coagulation of fulvic acids on colloids by Brownian
      dynamics simulations.
AB  - Humic substances (HS) play an important role in the reactivity and transport of
      colloids in natural environments. In particular, the presence of fulvic acids
      (FA) in natural waters modifies the interactions between inorganic particles and
      biopolymers and makes difficult to predict their stability with regard to
      aggregation processes. In this study, Brownian dynamics (BD) modeling is applied
      to quantify the interactions between negatively charged FA and (i) a positively
      charged inorganic particle and (ii) a rigid neutral polysaccharide in aqueous
      solutions. Hematite and schizophyllan are respectively used as model colloids.
      Modeling the adsorption of FA at the hematite particle surface and on the
      polysaccharide is based on van der Waals attractive forces and electrostatic
      interactions. Possible applications of the model, however, are not restricted to
      this system and any interaction potential or colloidal particle can be
      considered. The competition between FA adsorption and FA homocoagulation in
      solution is studied as function of the solution ionic strength. Results show
      that, under the conditions used, the amount of adsorbed FA is largely controlled
      by the solution ionic strength. At low ionic strength the amount of adsorbed FA
      is limited by the electrostatic repulsion between FA at the colloid surfaces and
      FA monolayers are formed. By increasing the ionic strength the number of adsorbed
      FA is found to increase. At a sufficiently large ionic strength, however, FA
      coagulation in solution may strongly compete with FA adsorption at the hematite
      and polysaccharide surfaces. FA aggregates then adsorb at the colloid surfaces to
      form extended and porous structures. Results also suggest that FA adsorption and
      structure of the adsorbed layers are mainly driven by the complex interplay
      between electrostatic attractive and repulsive interactions.

PMID- 19848133
TI  - Relating colloidal stability of fullerene (C60) nanoparticles to nanoparticle
      charge and electrokinetic properties.
AB  - The stability and aggregation kinetics of two different suspensions of fullerene
      (C60) nanoparticles and their relation to nanoparticle charge (electrokinetic)
      properties were investigated. The two synthesis methods employed--a solvent
      exchange method involving sonication of fullerene initially dissolved in toluene
      and prolonged stirring of bulk fullerene in water--produce negatively charged
      fullerene nanoparticles. With an increase in electrolyte (KCl) concentration, the
      electrophoretic mobilities of both fullerene nanoparticles became less negative,
      while the corresponding aggregation rates increased until maximum rates were
      reached at their respective critical coagulation concentrations. This behavior is
      consistent with the classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory for
      the stability of charged colloidal particles. The nanoparticles prepared by
      prolonged stirring of bulk fullerene in water were much more stable than those
      prepared by sonication in toluene, as evident from their significantly higher
      critical coagulation concentration (166 and 40 mM KCl, respectively). A
      comparison of the aggregation kinetics with predictions based on DLVO theory
      yielded the same Hamaker constant (8.5 x 10(-21) J) for both fullerene
      nanoparticles, indicating that they have the same material composition. Further
      investigation shows that both fullerene nanoparticles are more negatively charged
      and stable at higher pH conditions, suggesting that dissociation of surface
      functional groups contributes to surface charge for both nanoparticles. This
      hypothesis is further supported by oxidation which occurs on the surface of bulk
      fullerene that has been exposed to water over a prolonged period of time, as
      detected through X-ray photoelectron spectroscopy (XPS). However, since both
      nanoparticles remain negatively charged at pH 2, it is likely that there are
      other contributing factors to the surface charge of fullerene nanoparticles.

PMID- 19848134
TI  - Characterizing manufactured nanoparticles in the environment: multimethod
      determination of particle sizes.
AB  - Sizes of stabilized (24 h) nanoparticle suspensions were determined using several
      state-of-the-art analytical techniques (transmission electron microscopy; atomic
      force microscopy; dynamic light scattering; fluorescence correlation
      spectroscopy; nanoparticle tracking analysis; flow field flow fractionation).
      Theoretical and analytical considerations were evaluated, results were compared,
      and the advantages and limitations of the techniques were discussed. No "ideal"
      technique was found for characterizing manufactured nanoparticles in an
      environmental context as each technique had its own advantages and limitations.

PMID- 19848135
TI  - Silver nanoparticle impact on bacterial growth: effect of pH, concentration, and
      organic matter.
AB  - Silver nanoparticles (Ag NPs) are widely used as antibacterial agents. This
      antibacterial property carries with it a potential environmental risk once these
      NPs are discharged into the environment. This study investigated the impact on
      Pseudomonas fluorescens over a 24 h exposure of well characterized Ag NPs at pH
      values of 6-9, in the presence and absence of Suwannee River humic acids (SRHA).
      Ag NPs were characterized by size, aggregation, morphology, dissolution, and
      surface properties under all conditions. Solubility was low (less than 2%) for
      all Ag NP concentrations (2-2000 ppb) and under all conditions was less than 40
      ppb (0.38 microM). SRHA caused a partial disaggregation of Ag NP aggregates by
      nanoscale film formation, with individual NPs stabilized by charge and
      entropically driven steric effects. Dissolved Ag reduced bacterial growth
      entirely at 2000 ppb (19 microM) under all conditions and adversely affected
      growth at 200 ppb (1.9 microM) under some conditions, indicating some toxicity.
      The Ag NPs showed similar toxicity at 2000 ppb (19 microM) in the absence of SRHA
      and at pH 9 only i.e. SRHA mitigated bactericidal action. Solubility and
      interactions with SRHA indicate that there was a specific nanoparticle effect
      which could not be explained by the effect of dissolved Ag.

PMID- 19848136
TI  - Accumulation of cadmium in periphyton under various freshwater speciation
      conditions.
AB  - The relationship between cadmium speciation and accumulation in periphyton was
      examined at environmentally relevant Cd concentrations under natural freshwater
      conditions. Periphyton was exposed in artificial recirculating channels
      containing natural freshwater to two Cd concentrations (20 and 40 nM), for which
      speciation was modified by the addition of a synthetic organic ligand
      (nitrilotriacetate, NTA). Labile metal concentrations were measured with the
      technique of diffusion gradient in thin-films (DGT) and major Cd species were
      estimated by modeling. Total and intracellular Cd content in periphyton increased
      within both Cd exposure concentrations with NTA additions and were related to an
      increase in DGT-labile Cd, which was caused by the competition of NTA with
      probably colloidal species. Bioaccumulation was thus not controlled by the free
      Cd concentrations, as predicted by the free ion activity model, but by the
      diffusion of labile Cd-NTA complexes, which constituted a large fraction of DGT
      labile Cd. These findings confirm the importance of labile species for Cd
      accumulation in periphyton under freshwater conditions, as predicted by models
      considering diffusion and uptake kinetics.

PMID- 19848137
TI  - Greenhouse gas emissions from global cities.
AB  - The world's population is now over 50% urban, and cities make an important
      contribution to national greenhouse gas (GHG) emissions. Many cities are
      developing strategies to reduce their emissions. Here we ask how and why
      emissions differ between cities. Our study often global cities shows how a
      balance of geophysical factors (climate, access to resources, and gateway status)
      and technical factors (power generation, urban design, and waste processing)
      determine the GHGs attributable to cities. Within the overall trends, however,
      there are differences between cities with more or less public transit while
      personal income also impacts heating and industrial fuel use. By including
      upstream emissions from fuels, GHG emissions attributable to cities exceed those
      from direct end use by upto 25%. Our findings should help foster intercity
      learning on reducing GHG emissions.

PMID- 19848138
TI  - Life-cycle energy demand and global warming potential of computational logic.
AB  - Computational logic, in the form of semiconductor chips of the complementary
      metal oxide semiconductor (CMOS) transistor structure, is used in personal
      computers, wireless devices, IT network infrastructure, and nearly all modem
      electronics. This study provides a life-cycle energy analysis for CMOS chips over
      7 technology generations with the purpose of comparing energy demand and global
      warming potential (GWP) impacts of the life-cycle stages, examining trends in
      these impacts over time and evaluating their sensitivity to data uncertainty and
      changes in production metrics such as yield. A hybrid life-cycle assessment (LCA)
      model is used. While life-cycle energy and GWP of emissions have increased on the
      basis of a wafer or die, these impacts have been reducing per unit of
      computational power. Sensitivity analysis of the model shows that impacts have
      the highest relative sensitivity to wafer yield, line yield, and die size and
      largest absolute sensitivity to the use-phase power demand of the chip.

PMID- 19848139
TI  - Seasonal and daily source apportionment of polycyclic aromatic hydrocarbon
      concentrations in PM10 in a semirural European area.
AB  - Polycyclic aromatic hydrocarbons (PAH) were analyzed from ambient air particulate
      matter (PM10) that was collected near Lago Maggiore (Lombardy) in Northern Italy
      from August 2008 to January 2009. Highest individual PAH concentrations ranged
      from 0.05 ng/m3 during mid-days in summer to about 6 ng/m3 duringthe nights of
      the coldest period. A multivariate experimental regression model for the
      estimation of PAH concentrations was used to apportion the identified local
      sources of PAHs. This model included specific markers (i.e., levoglucosan for
      wood combustion and hopanes for traffic emission) and meteorological parameters
      (i.e., ambient air temperature and atmospheric mixing layer heights). In autumn
      and winter, wood combustion on a daily average contributed from 30 to 70% to the
      PAHs in ambient air PM10. In this period, the contribution of the wood combustion
      was less than 30% during mid-day, increasing sometimes to more than 80% during
      the night In the samples taken during the summer period, traffic contribution to
      PAH concentrations was about 30%, while wood combustion was insignificant.

PMID- 19848140
TI  - Perfluoroalkyl contaminants in window film: indoor/outdoor, urban/rural, and
      winter/summer contamination and assessment of carpet as a possible source.
AB  - Window film concentrations of ionic perfluoroalkyl contaminants (PFCs) were
      determined indoors and outdoors at urban, suburban, and rural sites in or near
      Toronto, Ontario, Canada, to identify locations of relatively elevated
      concentrations and the nature of potential sources. The role of carpet
      installation and floor wax application as possible sources was also evaluated by
      sampling indoor window films at five sites before and after new carpet
      installations, at one site before and after a floor wax application, and at two
      carpet stores. Low concentrations were found in all outdoor window films, with
      comparable relative proportions of individual PFCs among sites, suggesting
      similar sources to the outdoor environment and rapid air mixing. PFCs in indoor
      window film were up to 20-fold greater than outdoor, providing some evidence that
      a significant proportion of PFCs originate from the indoor environment, although
      precipitation wash-off of outdoor window film may be confounding these results.
      For both indoor and outdoor film, PFC concentrations generally changed between
      the summer and winter but the chemical profiles were similar between seasons.
      Concentrations of PFCs in window films increased one month post carpet
      installation at three of the five sites, suggesting that some of the carpets may
      have been a source to the indoor environment. Indoor window films from two carpet
      stores (sigmaPFC = 16 and 7 pg/cm2) contained higher concentrations than the
      other indoor locations (sigmaPFC = < MDL to 4.3 pg/cm2), which may reflect the
      carpets stored within these buildings. The use of window film allowed collection
      of a wide range of samples and the results can be used to focus the efforts of
      more traditional air sampling campaigns.

PMID- 19848141
TI  - Assessment of land use impact on water-related ecosystem services capturing the
      integrated terrestrial-aquatic system.
AB  - Although the importance of green (evaporative) water flows in delivering
      ecosystem services has been recognized, most operational impact assessment
      methods still focus only on blue water flows. In this paper, we present a new
      model to evaluate the effect of land use occupation and transformation on water
      quantity. Conceptually based on the supply of ecosystem services by terrestrial
      and aquatic ecosystems, the model is developed for, but not limited to, land use
      impact assessment in life cycle assessment (LCA) and requires a minimum amount of
      input data. Impact is minimal when evapotranspiration is equal to that of the
      potential natural vegetation, and maximal when evapotranspiration is zero or when
      it exceeds a threshold value derived from the concept of environmental water
      requirement. Three refinements to the model, requiring more input data, are
      proposed. The first refinement considers a minimal impact over a certain range
      based on the boundary evapotranspiration of the potential natural vegetation. In
      the second refinement the effects of evaporation and transpiration are accounted
      for separately, and in the third refinement a more correct estimate of
      evaporation from a fully sealed surface is incorporated. The simplicity and user
      friendliness of the proposed impact assessment method are illustrated with two
      examples.

PMID- 19848143
TI  - Effects of streambed morphology and biofilm growth on the transient storage of
      solutes.
AB  - Microbial biofilms are the prime site of nutrient and contaminant removal in
      streams. It is therefore essential to understand how biofilms affect hydrodynamic
      exchange, solute transport, and retention in systems where geomorphology end
      induced hydrodynamics shape their growth and structure. We experimented with
      large-scale streamside flumes with streambed landscapes constructed from graded
      bedforms of constant height and wavelength. Each flume had a different bedform
      height and was covered with a layer of gravel as substratum for benthic microbial
      biofilms. Biofilms developed different biomass and physical structures in
      response to the hydrodynamic conditions induced by the streambed morphology. Step
      injections of conservative tracers were performed at different biofilm growth
      stages. The experimental breakthrough curves were analyzed with the STIR model,
      using a residence time approach to characterize the retention effects associated
      with biofilms. The retained mass of the solute increased with biofilm biomass and
      the biofilm-associated retention was furthermore related to bedform height. We
      tentatively relate this behavior to biofilm structural differentiation induced by
      bed morphology, which highlights the strong linkage between geomorphology,
      hydrodynamics, and biofilms in natural streams and provide important clues for
      stream restoration.

PMID- 19848142
TI  - Isotopic variability of mercury in ore, mine-waste calcine, and leachates of mine
      waste calcine from areas mined for mercury.
AB  - The isotopic composition of mercury (Hg) was determined in cinnabar ore, mine
      waste calcine (retorted ore), and leachates obtained from water leaching
      experiments of calcine from two large Hg mining districts in the U.S. This study
      is the first to report significant mass-dependent Hg isotopic fractionation
      between cinnabar ore and resultant calcine. Data indicate that delta202Hg values
      relative to NIST 3133 of calcine (up to 1.52 per thousand) in the Terlingua
      district, Texas, are as much as 3.24 per thousand heavier than cinnabar (-1.72
      per thousand) prior to retorting. In addition, delta202Hg values obtained from
      leachates of Terlingua district calcines are isotopically similar to, or as much
      as 1.17 per thousand heavier than associated calcines, most likely due to
      leaching of soluble, byproduct Hg compounds formed during ore retorting that are
      a minor component in the calcines. As a result of the large fractionation found
      between cinnabar and calcine, and because calcine is the dominant source of Hg
      contamination from the mines studied, delta202Hg values of calcine may be more
      environmentally important in these mined areas than the primary cinnabar ore.
      Measurement of the Hg isotopic composition of calcine is necessary when using Hg
      isotopes for tracing Hg sources from areas mined for Hg, especially mine water
      runoff.

PMID- 19848144
TI  - Effect-directed analysis of contaminated sediments with partition-based dosing
      using green algae cell multiplication inhibition.
AB  - Effect-directed analysis (EDA) has been frequently and successfully used to
      identify key toxicants in sediment extracts. However, by disregarding
      bioavailability this approach may lead to a biased prioritisation of fractions
      and toxicants with respect to hazards and risks. To overcome this problem the
      present EDA of sediment components from the Bilina river (Most Czech Republic),
      that inhibit growth of the green algae Scenedesmus vacuolatus, applies a novel
      partition-based dosing technique to prioritize and identify major toxic fractions
      and compounds in comparison to conventional solvent dosing. The novel dosing
      technique is based on partitioning from loaded silicone rods to the aqueous phase
      similar to partition processes that determine exposure in native sediment-water
      systems. In the present study the application of partition-based dosing had a big
      influence suggesting polar compounds such as triclosan as key toxicants while
      polycyclic aromatic hydrocarbon (PAH) fractions did not exhibit significant
      effects. In contrast, conventional dosing prioritized mainly PAHs in agreement
      with previous studies. For both approaches individual toxicants could be
      confirmed quantitatively based on the index of confirmation quality (ICQ), which
      compares the effect of fractions and artificial mixtures of identified and
      quantified toxicants over the full range of effect levels.

PMID- 19848145
TI  - Polybrominated dibenzo-p-dioxins/ dibenzofurans and polybrominated diphenyl
      ethers in soil, vegetation, workshop-floor dust, and electronic shredder residue
      from an electronic waste recycling facility and in soils from a chemical
      industrial complex in eastern China.
AB  - The formation and release of polybrominated dibenzo-p-dioxins and dibenzofurans
      (PBDD/Fs) from the incineration of electronic wastes (e-waste) that contain
      brominated flame retardants (BFRs) are a concern. However, studies on the
      determination of PBDD/Fs in environmental samples collected from e-waste
      recycling facilities are scarce. In this study, 11 2,3,7,8-substituted PBDD/Fs
      and 10 polybrominated diphenyl ether (PBDE) congeners were determined in
      electronic shredder waste, workshop-floor dust soil, and leaves (of plants on the
      grounds of the facility) from a large-scale e-waste recycling facility and in
      surface soil from a chemical-industrial complex (comprising a coke-oven plant, a
      coal-fired power plant, and a chlor-alkali plant) as well as agricultural areas
      in eastern China. Total PBDD/F concentrations in environmental samples were in
      the range of 113-818 pg/g dry wt (dw) for leaves, 392-18500 pg/g dw for
      electronic shredder residues, 716-800000 pg/g dw for soil samples, and 89600-pg/g
      dw for workshop-floor dust from the e-waste recycling facility and in a range
      from nondetect (ND) to 427 pg/g dw in soil from the chemical-industrial complex.
      The highest mean concentrations of total PBDD/Fs were found in soil samples and
      workshop-floor dust from the e-waste recycling facility. The dioxin-like toxic
      equivalent (measured as TEQ) concentrations of PBDD/Fs were greater than the TEQs
      of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) reported in our
      previous study for the same set of samples. The concentrations of PBDFs were
      several orders of magnitude higher than the concentrations of PBDDs in samples
      from the e-waste facility or from soil from the chemical-industrial complex. A
      significant correlation was found between the concentrations of sigmaPBDD/Fs and
      sigmaPBDEs (r = 0.769, p < 0.01) and between sigmaPBDD/Fs and the previously
      reported sigmaPCDD/F concentrations (r = 0.805, p < 0.01). The estimated daily
      human intakes of TEQs contributed by PBDD/Fs via soil/dust ingestion and dermal
      exposures in e-waste recycling facilities were higher than the intakes of TEQs
      contributed by PCDD/ Fs, calculated in our previous study.

PMID- 19848146
TI  - Detection of S(IV) species in aerosol particles using XANES spectroscopy.
AB  - X-ray absorption near-edge structure spectroscopy (XANES) has been applied to the
      determination and quantification of S(IV) species in aerosol samples collected at
      Qingdao in northeastern China. The XANES spectra showed that sulfite was found
      only in particles with larger diameters (mineral aerosols) collected in August
      2001. Two oxidation treatments suggested that calcium sulfite (hannebachite) was
      the main S(IV) species in aerosols. No S(IV) species, however, were found at the
      surface of the aerosols as shown by surface-sensitive conversion electron/He ion
      yield XANES. The presence of hannebachite in the interior of aerosols
      demonstrates the importance of heterogeneous oxidation of SO2 (adsorption of SO2
      at the surface of mineral aerosols such as calcite with subsequent oxidation).
      The fact that this process is supported from XANES analysis for natural samples
      is important because sulfite formed by the adsorption of SO2 has only been
      detected in laboratory studies so far. The contribution of heterogeneous
      oxidation to the total rate of SO2 oxidation is not clear at present. However,
      this study suggests that the adsorption of SO2 on mineral aerosols without
      oxidation can reduce the oxidation of SO2 in the atmosphere, especially in the
      presence of calcite.

PMID- 19848147
TI  - Dissolved inorganic carbon export across the soil/stream interface and its fate
      in a boreal headwater stream.
AB  - The aim of this investigation was to determine the lateral exportof dissolved
      inorganic carbon (DIC) from soils of a Swedish boreal forest to a first order
      stream and to estimate the partitioning of this DIC into CO2 evasion from the
      stream surface and the DIC pool exported down through the catchment by
      streamwater. The groundwater entering the stream was supersaturated with CO2 with
      values as high as 17 times equilibrium with the atmosphere. Up to 90% of the
      estimated daily soil DIC export to the stream was emitted to the atmosphere as
      CO2 within 200 m of the water entering the stream. The annual DIC export from the
      soil to the stream was estimated to be 3.2 (+/- 0.1) g C m(-2) yr(-1) (normalized
      to catchment size). Ninety percent of the variation in soil DIC export could be
      explained by the variation in groundwater discharge and the DIC concentrations
      per se, were of minor importance. A significant correlation (R(l) = 0.74, P <
      0.01) between soil DIC export and CO2 emission from the stream surface suggests
      that emission dynamics were primarily driven by the export of terrestrial DIC and
      that in-stream processes were less important. Our results reveal that current
      budget estimates of lateral DIC export from soils to aquatic conduits need to be
      revised because they do not account for conditions prevailing in headwater
      streams. Any quantification of lateral stream C export and CO2 emissions from
      freshwater systems must include headwater streams as well as the lower parts of
      the aquatic conduit.

PMID- 19848148
TI  - Sorption of Buckminsterfullerene (C60) to saturated soils.
AB  - With the increasing use of C60 in many industrial and commercial sectors, it is
      likely that it will eventually appear in the environment however, its
      environmental fate and transport is still largely unknown. The extent to which
      C60 partitions to soil will contribute to its environmental fate and
      bioavailability. Because C60 is extremely hydrophobic, in this study the
      distribution between soil and mixtures of ethanol (EOH) and water were measured
      at ethanol mole fractions ranging from X(EOH) = 1.0-0.4 for two soils. By
      measuring K(p) at X(EOH) = 1.0 for a series of soils that ranged in organic
      carbon and clay mineral content, possible mineral contribution to the overall
      partition process was found for some of the soils. After correcting for any
      mineral contribution to sorption, the organic carbon normalized partition
      coefficient, K(oc), at each value of X(EDH) was calculated from the measured K(p)
      values. Through a classical thermodynamic relationship, the K(oc) values
      determined at X(EOH) = 1.0-0.4 were extrapolated to estimate the pure water
      (i.e., X(EOH) = 0) K(oc) value of 10(7.1) (L/kg). Accounting for any dissolved
      organic matter (DOM) in any pure water-soil mixtures may lower this estimate by
      over a factor of 2, placing this estimate in good agreement with C60's octanol
      water partition coefficient, K(ow) (= 10(6.7)).

PMID- 19848149
TI  - Impact of higher alginate expression on deposition of Pseudomonas aeruginosa in
      radial stagnation point flow and reverse osmosis systems.
AB  - Extracellular polymeric substances (EPS) have major impact on biofouling of
      reverse osmosis (RO) membranes. On one hand, EPS can reduce membrane permeability
      and on the other, EPS production by the primary colonizers may influence their
      deposition and attachment rate and subsequently affect the biofouling propensity
      of the membrane. The role of bacterial exopolysaccharides in bacterial deposition
      followed by the biofouling potential of an RO membrane was evaluated using an
      alginate overproducing (mucoid) Pseudomonas aeruginosa. The mucoid P. aeruginosa
      PAOmucA22 was compared with its isogenic nonmucoid prototypic parent PAO1
      microscopically in a radial stagnation point flow (RSPF) system for their
      bacterial deposition characteristics. Then, biofouling potential of PAO1 and
      PAOmucA22 was determined in a crossflow rectangular plate-and-frame membrane
      cell, in which the strains were cultivated on a thin-film composite, polyamide,
      flat RO membrane coupon (LFC-1) under laminar flow conditions. In the RSPF
      system, the observed deposition rate of the mucoid strain was between 5- and 10
      fold lower than of the wild type using either synthetic wastewater medium (with
      ionic strength of 14.7 mM and pH 7.4) or 15 mM KCl solution (pH of 6.2). The
      slower deposition rate of the mucoid strain is explained by 5- to 25-fold
      increased hydrophilicity of the mucoid strain as compared to the isogenic wild
      type, PAO1. Corroborating with these results, a significant delay in the onset of
      biofouling of the RO membrane was observed when the mucoid strain was used as the
      membrane colonizer, in which the observed time for the induced permeate flux
      decline was delayed (ca. 2-fold). In conclusion, the lower initial cell
      attachment of the mucoid strain decelerated biofouling of the RO membrane.
      Bacterial deposition and attachment is a critical step in biofilm formation and
      governed by intimate interactions between outer membrane proteins of the bacteria
      and the surface. Shielding these interactions by a hydrated and hydrophilic
      alginate capsule is shown to dramatically lessen the biofouling potential of the
      membrane colonizers.

PMID- 19848150
TI  - XANES evidence for oxidation of Cr(III) to Cr(VI) by Mn-oxides in a lateritic
      regolith developed on serpentinized ultramafic rocks of New Caledonia.
AB  - Although several laboratory studies showed that Mn-oxides are capable of
      oxidizing Cr(II) to Cr(VI), very few have reported evidence for such a reaction
      in natural systems. This study presents new evidence for this redox reaction
      between Cr(III) and Mn-oxides in a lateritic regolith developed on ultramafic
      rocks in New Caledonia. The studied lateritic regolith presents several units
      with contrasting amounts of major (Fe, Al, Si, and Mg) and trace (Mn, Cr, Ni, Co)
      elements, which are related to varying mineralogical compositions. Bulk XANES
      analyses show the occurrence of Cr(VI) (up to 20 wt % of total chromium) in the
      unit of the regolith which is also enriched in Mn (up to 21.7 wt % MnO), whereas
      almost no Cr(VI) is detected elsewhere. X-ray powder diffraction indicates that
      the large amounts of Mn in this unit of the regolith are due to the occurrence of
      Mn-oxides (identified as a mixture of asbolane, lithiophorite and birnessite) and
      Mn K-edge XANES data indicate that Mn occurs mainly as Mn(IV) in this unit,
      although small amounts of Mn(III) could also be detected. These results strongly
      suggest a direct role of the Mn-oxides on the occurrence of Cr(VI) through a
      redox reaction between Cr(III) and Mn(IV) and/or Mn(III). Owing to the much
      larger toxicity and solubility of Cr(VI), such a co-occurrence of Cr and Mn
      oxides in these soils could then represent an important risk for the environment.
      However, the significant amounts of Cr(VI) released after reacting the samples
      from the studied sequence with a 0.1 M (NH)4H2PO4 solution, designed to remove
      tightly sorbed chromate species, suggest that Cr(VI) mainly occurs as sorption
      complexes. This hypothesis is reinforced by spatially resolved XANES analyses,
      which show that Cr(VI) is associated with both Mn- and Fe-oxides, and especially
      at the boundary between these two mineral species. Such a distribution of Cr(VI)
      suggests a possible readsorption of Cr(VI) onto surrounding Fe-oxyhydroxides
      (mainly goethite) after oxidation by the Mn(IV)-oxides. These results, added to
      leaching tests with a 0.01 M CaCl2 solution indicative of low exchangeability of
      Cr in the investigated samples, suggest that secondary sorption reactions onto Fe
      oxides might significantly decrease the environmental impact of the oxidation of
      Cr(III) to Cr(VI) by Mn-oxides.

PMID- 19848151
TI  - Incorporation of oxidized uranium into Fe (hydr)oxides during Fe(II) catalyzed
      remineralization.
AB  - The form of solid phase U after Fe(II) induced anaerobic remineralization of
      ferrihydrite in the presence of aqueous and absorbed U(VI) was investigated under
      both abiotic batch and biotic flow conditions. Experiments were conducted with
      synthetic ground waters containing 0.168 mM U(VI), 3.8 mM carbonate, and 3.0 mM
      Ca2+. In spite of the high solubility of U(VI) under these conditions,
      appreciable removal of U(VI) from solution was observed in both the abiotic and
      biotic systems. The majority of the removed U was determined to be substituted as
      oxidized U (U(VI) or U(V)) into the octahedral position of the goethite and
      magnetite formed during ferrihydrite remineralization. It is estimated that
      between 3 and 6% of octahedral Fe(III) centers in the new Fe minerals were
      occupied by U. This site specific substitution is distinct from the nonspecific U
      coprecipitation processes in which uranyl compounds, e.g., uranyl hydroxide or
      carbonate, are entrapped within newly formed Fe oxides. The prevalence of site
      specific U incorporation under both abiotic and biotic conditions and the fact
      that the produced solids were shown to be resistant to both extraction (30 mM
      KHCO3) and oxidation (air for 5 days) suggest the potential importance of
      sequestration in Fe oxides as a stable and immobile form of U in the environment.

PMID- 19848152
TI  - Using X-ray microscopy and Hg L3 XANES to study Hg binding in the rhizosphere of
      Spartina cordgrass.
AB  - San Francisco Bay has been contaminated historically by mercury from mine
      tailings as well as contemporary industrial sources. Native Spartina foliosa and
      non-native S. alterniflora-hybrid cordgrasses are dominant florae within the SF
      Bay estuary environment. Understanding mercury uptake and transformations in
      these plants will help to characterize the significance of their roles in mercury
      biogeochemical cycling in the estuarine environment. Methylated mercury can be
      biomagnified up the food web, resulting in levels in sport fish up to 1 million
      times greater than in surrounding waters and resulting in advisories to limit
      fish intake. Understanding the uptake and methylation of mercury in the plant
      rhizosphere can yield insight into ways to manage mercury contamination. The
      transmission X-ray microscope on beamline 6-2 at the Stanford Synchrotron
      Radiation Lightsource (SSRL) was used to obtain absorption contrast images and 3D
      tomography of Spartina foliosa roots that were exposed to 1 ppm Hg (as HgCl2)
      hydroponically for 1 week. Absorption contrast images of micrometer-sized roots
      from S. foliosa revealed dark particles, and dark channels within the root, due
      to Hg absorption. 3D tomography showed that the particles are on the root
      surface, and slices from the tomographic reconstruction revealed that the
      particles are hollow, consistent with microorganisms with a thin layer of Hg on
      the surface. Hg L3 XANES of ground-up plant roots and Hg L3 micro-XANES from
      microprobe analysis of micrometer-sized roots (60-120 microm in size) revealed
      three main types of speciation in both Spartina species: Hg-S ligation in a form
      similar to Hg(II) cysteine, Hg-S bonding as in cinnabar and metacinnabar, and
      methylmercury-carboxyl bonding in a form similar to methylmercury acetate. These
      results are interpreted within the context of obtaining a "snapshot" of mercury
      methylation in progress.

PMID- 19848153
TI  - Magnetic enzyme carrier for effective biofouling control in the membrane
      bioreactor based on enzymatic quorum quenching.
AB  - Quorum quenching, enzymatic quenching of bacterial quorum sensing, has recently
      proven its potential as a novel approach of biofouling control in the membrane
      bioreactor (MBR) for advanced wastewater treatment. However, the short catalytic
      lifetime and difficulty in recovering free enzyme hamper the successful
      application of the quorum quenching technique in the MBR under a long-term
      continuous operation. In this study, a magnetic enzyme carrier (MEC) was prepared
      by immobilizing the quorum quenching enzyme (acylase) on magnetic particles to
      overcome the technical limitations of free enzyme. The MEC showed no activity
      decrease under both continuous shaking for 14 days and 29 iterative cycles of
      reuse. Furthermore, the comparison of the MEC with free enzyme in a batch type
      MBR showed that the MEC efficiently alleviated the membrane biofouling and showed
      a great advantage over free enzyme in terms of recycled use and stability in
      mixed liquor. When the MEC was applied to the lab scale MBR in a continuous
      operation, it also enhanced the membrane permeability to a large extent compared
      with a conventional MBR with no enzyme.

PMID- 19848154
TI  - Escherichia coli inactivation by water-soluble, ozonated C60 derivative: kinetics
      and mechanisms.
AB  - Antibacterial and bactericidal effects of a C60 derivative prepared via excess
      ozonation of C60 aggregates in water were investigated using Escherichia coli as
      a representative microorganism. Ozonated C60 up to 10 mg/L did not cause
      significant growth inhibition nor inactivation of E. coli in the absence of
      either oxygen or light. However, it readily inactivated E. coli in the presence
      of both oxygen and light at much faster rate than parent C60 aggregates,
      suggesting involvement of photochemical generation of reactive oxygen species
      (ROS). Among ROS, hydroxyl radical was found as a primary agent for the cell
      inactivation. Little surface protein release and concurrent intercellular enzyme
      degradation during the course of E. coli inactivation, along with visual evidence
      obtained from transmission electron microscopic analysis, collectively indicated
      that the mechanism of E. coli inactivation by ozonated C60 involves efficient
      penetration of ozonated C60 into E. coli and subsequent photochemical production
      of hydroxyl radical within the cell cytoplasm. These findings suggest that
      oxidative transformation of C60 can lead to increased toxicity in addition to
      increased water solubility and reduced size, warranting further studies on other
      potential chemical derivatization possible in natural and engineered environments
      for an accurate assessment of environmental impact of this class of materials.

PMID- 19848155
TI  - Thermodynamic properties of autunite, uranyl hydrogen phosphate, and uranyl
      orthophosphate from solubility and calorimetric measurements.
AB  - In this study, we use solubility and drop-solution calorimetry measurements to
      determine the thermodynamic properties of the uranyl phosphate phases autunite,
      uranyl hydrogen phosphate, and uranyl orthophosphate. Conducting the solubility
      measurements from both supersaturated and undersaturated conditions and under
      different pH conditions rigorously demonstrates attainment of equilibrium and
      yields well-constrained solubility product values. We use the solubility data and
      the calorimetry data, respectively, to calculate standard-state Gibbs free
      energies of formation and standard-state enthalpies of formation for these uranyl
      phosphate phases. Combining these results allows us also to calculate the
      standard-state entropy of formation for each mineral phase. The results from this
      study are part of a combined effort to develop reliable and internally consistent
      thermodynamic data for environmentally relevant uranyl minerals. Data such as
      these are required to optimize and quantitatively assess the effect of phosphate
      amendment remediation technologies for uranium contaminated systems.

PMID- 19848156
TI  - Surface complexation of carboxylate adheres Cryptosporidium parvum oocysts to the
      hematite-water interface.
AB  - The interaction of viable Cryptosporidium parvum oocysts at the hematite (alpha
      Fe2O3)-water interface was examined over a wide range in solution chemistry using
      in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR)
      spectroscopy. Spectra for hematite-sorbed oocysts showed distinct changes in
      carboxylate group vibrations relative to spectra obtained in the absence of
      hematite, indicative of direct chemical bonding between carboxylate groups and Fe
      metal centers of the hematite surface. The data also indicate that complexation
      modes vary with solution chemistry. InNaCl solution, oocysts are bound to
      hematite via monodentate and binuclear bidentate complexes. The former
      predominates at low pH, whereas the latter becomes increasingly prevalent with
      increasing pH. In a CaCl2 solution, only binuclear bidentate complexes are
      observed. When solution pH is above the point of zero net proton charge (PZNPC)
      of hematite, oocyst surface carboxylate groups are bound to the mineral surface
      via outer-sphere complexes in both electrolyte solutions.

PMID- 19848157
TI  - Cadmium(II) speciation in complex aquatic systems: a study with ferrihydrite,
      bacteria, and an organic ligand.
AB  - Understanding the chemical interactions that occur in complex natural systems is
      fundamental to their management In this work the distribution of cadmium in the
      presence of phthalic acid (H2Lp), ferrihydrite, and bacteria cells (Comamonas
      spp., heat killed) was measured and modeled for systems with incrementally
      increasing complexity. In binary systems, cadmium adsorption onto bacteria or
      ferrihydrite was accurately predicted using the nonelectrostatic four site model
      (NFSM) and the diffuse layer model (DLM), respectively. Phthalic acid (0.6 mM)
      enhanced Cd2+ adsorption onto ferrihydrite (due to surface ternary complex
      formation) butinhibited Cd2 adsorption onto bacteria to the same extent as
      predicted by Cd-phthalate solution complex formation constants, implying no
      significant surface ternary interaction occurred in this system. In Cd
      ferrihydrite-bacteria systems, Cd2+ adsorption was up to 10% lower than that
      predicted by additive adsorption onto the pure phases which suggests that an
      interaction between ferrihydrite and the bacteria is occupying or masking
      adsorption sites. By adding a generic reaction to the model for the interaction
      between ferrihydrite and the bacteria, the adsorption of Cd2+ onto Comamonas spp.
      ferrihydrite was accurately predicted and Cd2+ distribution and speciation in
      systems containing ferrihydrite, Comamonas spp., and H2Lp could be predicted.

PMID- 19848158
TI  - Photochemistry of atmospheric dust: ozone decomposition on illuminated titanium
      dioxide.
AB  - The ozone decomposition onto mineral surfaces prepared with traces of solid TiO2
      in a matrix of SiO2 in order to mimic mineral dust particles has been
      investigated using a coated-wall flow-tube system at room temperature and
      atmospheric pressure. The ozone uptake coefficients were measured both under dark
      conditions and irradiation using near UV-light. While uptake in the dark was
      negligible, a large photoenhanced ozone uptake was observed. For TiO2/SiO2
      mixtures under irradiation, the uptake coefficients increased with increasing
      TiO2 mass fraction (from 1 to 3 wt %), and the corresponding uptake coefficient
      based on the geometric surfaces ranged from 3 x 10(-6) to 3 x 10(-5). The uptake
      kinetics was also observed to increase with decreasing ozone concentration
      between 290 and 50 ppbv. Relative humidity influenced the ozone uptake on the
      film, and a reduced ozone loss was observed for relative humidity above 30%. The
      experimental results suggest that under atmospherically relevant conditions the
      photochemistry of dust can represent an important sink of ozone inside the dust
      plume.

PMID- 19848159
TI  - Perfluorinated carboxylates and sulfonates and precursor compounds in herring
      gull eggs from colonies spanning the Laurentian Great Lakes of North America.
AB  - Environmentally important perfluorinated carboxylates and sulfonates, as well as
      per- and polyfluorinated precursor compounds including several sulfonamides,
      telomer acids, and alcohols were determined in individual herring gull (Larus
      argentatus) eggs collected (in 2007) from 15 colonies located at Canadian and
      some American sites across the Laurentian Great Lakes of North America. The
      pattern of perfluorosulfonates (PFSAs; C6, C8, C10 chain lengths) was dominated
      by PFOS (> 90% of sigmaPFSA concentration) regardless of collection location.
      Concentrations of sigmaPFSA were significantly (p < 0.03) higher in eggs from
      Middle Island (western Lake Erie; 507 +/- 47 ng/g ww), Toronto Harbour (484 +/-
      49 ng/g ww), and Strachan Island (486 +/- 59 ng/g ww) (Lake Ontario) compared to
      eggs from colonies on Lakes Superior, Michigan, and Huron. Perfluorocarboxylic
      acids (PFCAs) ranging in chain length from C8 to C15 were detected in the eggs,
      with PFUnA and PFTrA being the dominant compounds. PFOA and PFNA were more
      abundant in the sigmaPFCA in eggs from Lake Superior and Michigan colonies, and
      PFUnA and longer chain PFCAs were more abundant in the sigmaPFCA in eggs from
      Lake Erie and Ontario colonies. In contrast to sigmaPFSA, the highest
      concentrations of sigmaPFCA were found in eggs from Double Island, Lake Huron
      (113 +/- 12 ng/g ww) followed by eggs from colonies on Lakes Erie and Ontario.
      Among the PFOS or PFCA precursor compounds assessed (6:2, 8:2, and 10:2
      fluorotelomer alcohols and acids and PFOSA), none were detectable in eggs from
      any sampling location. The exception was PFOSA (average concentration < 1 ng/g
      ww), which suggests that PFOS in the gulls and subsequently in their eggs may be
      due, in part, to biotransformation of PFOSA to PFOS in the gull and/or in their
      diet and food web. The accumulation of PFSA and PFCA from mainly aquatic dietary
      sources was suggested, and were highly lake- and/ or colony-dependent especially
      showing a northwest and southeast spatial trend and with higher concentrations in
      eggs from colonies in close proximity to highly urbanized and industrialized
      sites in Lakes Erie and Ontario.

PMID- 19848160
TI  - Assessing coastal plumes in a region of multiple discharges: the U.S.-Mexico
      border.
AB  - The San Diego/Tijuana border region has several environmental challenges with
      regard to assessing water quality impacts resulting from local coastal ocean
      discharges for which transport is not hindered by political boundaries. While an
      understanding of the fate and transport of these discharged plumes has a broad
      audience, the spatial and temporal scales of the physical processes present
      numerous challenges in conducting assessment with any fidelity. To address these
      needs, a data-driven model of the transport of both shoreline and offshore
      discharges is developed and operated in a hindcast mode for a four-year period to
      analyze regional connectivity between the discharges and the receiving of waters
      and the coastline. The plume exposure hindcast model is driven by surface current
      data generated by a network of high-frequency radars. Observations provided by
      both boat-based CTD measurements and fixed oceanographic moorings are used with
      the Roberts-Snyder-Baumgartner model to predict the plume rise height. The
      surface transport model outputs are compared with shoreline samples of fecal
      indicator bacteria (FIB), and the skill of the model to assess low water quality
      is evaluated using receiver operating characteristic (ROC) analysis.

PMID- 19848161
TI  - Aerobic biodegradation of chlorinated ethenes in a fractured bedrock aquifer:
      quantitative assessment by compound-specific isotope analysis (CSIA) and reactive
      transport modeling.
AB  - A model-based analysis of concentration and isotope data was carried out to
      assess natural attenuation of chlorinated ethenes in an aerobic fractured bedrock
      aquifer. Tetrachloroethene (PCE) concentrations decreased downgradient of the
      source, but constant delta13C signatures indicated the absence of PCE
      degradation. In contrast, geochemical and isotopic data demonstrated degradation
      of trichloroethene (TCE) and cis-1,2-dichloroethene (DCE) under the prevailing
      oxic conditions. Numerical modeling was employed to simulate isotopic enrichment
      of chlorinated ethenes and to evaluate alternative degradation pathway scenarios.
      Existing field information on groundwater flow, solute transport, geochemistry,
      and delta13C signatures of the chlorinated ethenes was integrated via reactive
      transport simulations. The results provided strong evidence for the occurrence of
      aerobic TCE and DCE degradation. The chlorinated ethene concentrations together
      with stable carbon isotope data allowed us to reliably constrain the assessment
      of the extent of biodegradation at the site and plume simulations quantitatively
      linked aerobic biodegradation with isotope signatures in the field. Our
      investigation provides the first quantitative assessment of aerobic
      biodegradation of chlorinated ethenes in a fractured rock aquifer based on
      compound specific stable isotope measurements and reactive transport modeling.

PMID- 19848162
TI  - Modeling the effect of surface heterogeneity in equilibrium of heavy metal ion
      biosorption by using the ion exchange model.
AB  - This paper is focused on the theoretical modeling of the heavy metal ions
      biosorption process. The origin of the commonly observed, so-called
      "heterogeneity effects" has been explained. Two popular models were considered
      for that purpose: the adsorption model and the ion exchange model. The
      Condensation Approximation method has been used to develop the model describing
      the influence of surface heterogeneity on biosorption equilibria. As this model
      has been derived by accepting the ion exchange processes on the biosorbent
      surface, the obtained expressions are able to also take into account the pH
      effect. The mentioned "heterogeneity effects" may be treated as the result of (i)
      the existence of the continuous function expressing the binding site
      heterogeneity, (ii) the existence of a few different kinds of binding sites,
      having different values of ion exchange constant; (iii) stoichiometry of the ion
      exchange reaction occurring on the biosorbent surface. The latter case is
      responsible for the so-called "apparent" heterogeneity, when the adsorption model
      and the ion exchange model offer equally good fits of data but the degree of the
      surface heterogeneity estimated in this way might be different.

PMID- 19848163
TI  - Chemical tracers of particulate emissions from commercial shipping.
AB  - Despite the increase of commercial shipping around the world, data are yet
      relatively scarce on the contribution of these emissions to ambient air
      particulates. One of the reasons is the complexity in the detection and
      estimation of shipping contributions to ambient particulates in harbor and urban
      environments, given the similarity with tracers of other combustion sources. This
      study aimed to identify specific tracers of shipping emissions in a Mediterranean
      city with an important harbor (Melilla, Spain). Results showed that for 24 h PM10
      and PM2.5 samples, valid tracers of commercial shipping emissions were ratios of
      V/Ni = 4-5 and V/EC < 2, whereas V/EC > 8 excluded the influence of shipping
      emissions. Other ratios (V/ S, La/Ce, Zn/Ni, Pb/Zn, OC/EC) and tracers (Pb, Zn)
      were also tested but did not correlate with this source. Due to the changing
      composition of diesel fuels, tracers in the Mediterranean Sea may not be
      representative in other regions of the world and vice versa. The contribution of
      shipping emissions to ambient particulate matter (PM) urban background levels was
      quantified by positive matrix factorization (PMF), resulting in 2% and 4% of mean
      annual PM10 levels (0.8 microg/m3 primary particles and 1.7 microg/m3 secondary
      particles, with 20% uncertainty) and 14% of mean annual PM2.5 levels (2.6
      microg/m3).

PMID- 19848164
TI  - Application of a bioassay using DR-EcoScreen cells to the determination of
      dioxins in ambient air: a comparative study with HRGC-HRMS analysis.
AB  - There is a strong need for the development of relatively rapid and low-cost
      bioassays for the determination of dioxins (polychlorinated dibenzo-p-dioxins,
      dibenzofurans, and dioxin-like polychlorinated biphenyls) in environmental and
      food samples. In this study, we applied a bioassay system using highly sensitive
      DR-EcoScreen cells (DR-cell assay) to the determination of low levels of dioxins
      in ambient air samples. The dioxins from 80 ambient air samples were extracted,
      purified by cleanup procedure, and applied to both DR-cell assay and high
      resolution gas chromatography/high-resolution mass spectrometry (HRGC-HRMS)
      analysis. Interestingly, the toxic equivalents (TEQ) values obtained from the DR
      cell assay were closely correlated with those from the HRGC-HRMS analysis (r2 =
      0.957). Although the cell-based TEQ values were relatively (3.66-fold) higher
      than the TEQ values from the HRGC-HRMS analysis, this discrepancy was thought to
      be due to the difference between the toxic equivalency factor (TEF) and the
      relative potency (DR-REP) determined for individual dioxins. Therefore, we
      multiplied the TEQ values from the DR-cell assay by a conversion coefficient
      (0.273, the reciprocal of 3.66) and could approximate the values from the HRGC
      HRMS analysis. These results clearly suggest at the DR-cell assay might be a
      promising method for the rapid and low-cost screening of dioxins in ambient air
      samples.

PMID- 19848165
TI  - Development and first results of an aircraft-based, high time resolution
      technique for gaseous elemental and reactive (oxidized) gaseous mercury.
AB  - We developed a high time resolution (2.5 min) aircraft instrument for gaseous
      elemental mercury (GEM) and reactive gaseous mercury (RGM). The system measures
      RGM with complementary denuder and difference techniques, which can be compared
      to check for consistency. In laboratory tests, the agreement of the two
      techniques was 15% (+/- 13%). In five test flights, RGM was generally below the
      detection limit of the difference technique (0.08-0.16 ng/m3) except for values
      of 200-500 pg/m3 in airmasses between 600-700 mb (Flight 1) and 850-550 mb (Right
      4), which is consistent with previous observations of RGM at Mt Bachelor. There
      was a linear correlation between the denuder and difference techniques in each
      flight (range of slopes, 0.27-1.24) and across all flights (slope = 0.37, p < 1e
      6). The correlation is evidence that the difference technique is able to measure
      RGM in real time, although RGM appears to not be fully captured or recovered by
      the denuder. The only factor common to all RGM enhancements was the low aerosol
      scattering coefficient (< 2 M/m). Particulate mercury was below the detection
      limit (27 pg/m3) for all samples. The mean GEM and total mercury (THg) profiles
      are in the middle of the range of other published profiles. The THg profile
      showed no gradient to 5.5 km (p = 0.12, r2 = 0.009).

PMID- 19848167
TI  - Photoelectrocatalytic removal of bromate using Ti/TiO2 coated as a photocathode.
AB  - These studies represent the rare use of a TiO2 material as a photocathode and the
      first application of photoelectrocatalysis for BrO3- removal.
      Photoelectrocatalytic reduction of BrO3- to Br- can reach 70% at neutral pH under
      an applied potential of -0.20 V versus SCE (saturated calomel electrode) after 75
      min on the irradiated nanoporous thin-film TiO2-coated working electrode, which
      presented a flat band potential of -0.0274 V versus SCE. Regardless of the
      potential applied in these experiments, no BrO3- removal was observed in the
      counter electrode compartment or during electrolysis or photocatalysis,
      confirming that reduction of BrO3- to Br requires the combination of a negative
      potential (ideally near -0.20 V) and ultraviolet irradiation of the Ti/TiO2
      electrode. The process was selective for BrO3- removal in that this process did
      not significantly reduce levels of Ca2+ and Mg2+ in drinking waters.

PMID- 19848166
TI  - Detection of organophosphate flame retardants in furniture foam and U.S. house
      dust.
AB  - Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted
      in the increased use of alternate flame retardant chemicals to meet flammability
      standards. However, it has been difficult to determine which chemical
      formulations are currently being used in high volumes to meet flammability
      standards since the use of flame retardant formulations in consumer products is
      not transparent (i.e., not provided to customers). To investigate chemicals being
      used as replacements for PentaBDE in polyurethane foam, we analyzed foam samples
      from 26 different pieces of furniture purchased in the United States primarily
      between 2003 and 2009. Samples included foam from couches, chairs, mattress pads,
      pillows, and, in one case, foam from a sound-proofing system of a laboratory
      grade dust sieve, and were analyzed using gas chromatography mass spectrometry.
      Fifteen of the foam samples contained the flame retardanttris(1,3-dichloro-2
      propyl) phosphate (TDCPP; 1-5% by weight), four samples contained tris(1-chloro-2
      propyl) phosphate (TCPP; 0.5 -22% by weight), one sample contained brominated
      chemicals found in a new flame retardant mixture called Firemaster 550 (4.2% by
      weight), and one foam sample collected from a futon likely purchased prior to
      2004 contained PentaBDE (0.5% by weight). Due to the high frequency of detection
      of the chlorinated phosphate compounds in furniture foam,we analyzed extracts
      from 50 house dust samples collected between 2002 and 2007 in the Boston, MA area
      for TDCPP, TCPP, and another high volume use organophosphate-based flame
      retardant used in foam, triphenylphosphate (TPP). Detection frequencies for TDCPP
      and TPP in the dust samples were > 96% and were log normally distributed, similar
      to observations for PBDEs. TCPP was positively detected in dust in only 24% of
      the samples, but detection was significantly limited by a coelution problem. The
      geometric mean concentrations for TCPP, TDCPP, and TPP in house dust were 570,
      1890, and 7360 ng/g, respectively, and maximum values detected in dust were 5490,
      56,080 and 1,798,000 ng/g, respectively. These data suggest that levels of these
      organophosphate flame retardants are comparable, or in some cases greater than,
      levels of PBDEs in house dust. The high prevalence of these chemicals in foam and
      the high concentrations measured in dust (as high as 1.8 mg/g) warrant further
      studies to evaluate potential health effects from dust exposure, particularly for
      children.

PMID- 19848168
TI  - In vivo biotransformation of 3,3',4,4'-tetrachlorobiphenyl by whole plants
      poplars and switchgrass.
AB  - Polychlorinated biphenyls (PCBs) are widely distributed persistent organic
      pollutants. In vitro research has shown that plant cell cultures might transform
      lower chlorinated congeners to hydroxylated PCBs, but there are few studies on in
      vivo metabolism of PCBs by intact whole plants. In this research, poplar plants
      (Populus deltoides x nigra, DN34) and switchgrass (Panicum vigratum, Alamo) were
      hydroponically exposed to 3,3',4,4'-tetrachlorobiphenyl (CB77). Metabolism in
      plants occurred rapidly, and metabolites were detected after only a 24 h
      exposure. Rearrangement of chlorine atoms and dechlorination of CB77 by plants
      was unexpectedly observed. In addition, poplars were able to hydroxylate CB77 and
      the metabolite 6-hydroxy-3,3,4,4'-tetrachlorobiphenyl 6-OH-CB77) was identified
      and quantified. Hybrid poplar was able to hydroxylate CB77, but switchgrass was
      not, suggesting that enzymatic transformations are plant specific. Sulfur
      containing metabolites (from the action of sulfotransferases) were investigated
      in this study, but they were not detected in either poplar or switchgrass.

PMID- 19848169
TI  - Catalytic role of palladium and relative reactivity of substituted chlorines
      during adsorption and treatment of PCBs on reactive activated carbon.
AB  - The adsorption-mediated dechlorination of polychlorinated biphenyls (PCBs) is a
      unique feature of reactive activated carbon (RAC). Here, we address the RAC
      system, containing a tunable amount of Fe as a primary electron donor coupled
      with Pd as an electrochemical catalyst to potentially respond to the
      characteristic of contaminated sites, effectively traps and treats various PCB
      congeners. A dramatic increase in RAC reactivity with Pd doping at as low as
      0.01% suggests its critical role for accelerating hydrodechlorination of PCBs.
      Characteristic adsorption and dechlorination behavior and ensuing decomposition
      pathways of 13 selected PCB congeners are discussed with their surface
      interactions with RAC. Important findings include (i) inherent dechlorination
      susceptibility of chlorines in para > meta > ortho position, regardless of
      independent or competitive conditions as well as substrate effects, (ii)
      favorable reduction of more toxic coplanar PCB congeners, (iii) preferential
      electrophilic attack to chlorines in a less substituted phenyl ring and an
      isolated chlorine, regardless of the steric or inductive effect as a dominant
      limiting factor for the dechlorination of ortho or meta PCBs, respectively, (iv)
      prominent dechlorination inhibition for higher ortho congeners but negligible
      inhibition for higher meta congeners, and (v) eventual complete dechlorination of
      higher PCB congeners to biphenyl.

PMID- 19848170
TI  - Sequestering uranium and technetium through co-precipitation with aluminum in a
      contaminated acidic environment.
AB  - This research evaluated a method of controlled base addition for immobilizing
      uranium (U) and technetium (Tc) through coprecipitation with aluminum (Al) and
      other metal ions which coexist in a highly contaminated acidic environment. The
      batch and column experiments indicate that the addition of strong base (NaOH)
      provided a rapid yet effective means of sequestering U, Tc, and toxic metal ions
      such as nickel (Ni2+) and cobalt (Co2+) in the sediment and groundwater. Greater
      than 94% of soluble U (as UO2(2+)) and > 83% of Tc (as TcO4-) can be immobilized
      at pH above 4.5 by co-precipitation with Al-oxyhydroxides. The presence of
      sediment minerals appeared to facilitate co-precipitation of these contaminants
      at lower pH values than those in the absence of sediments. The immobilized U and
      Tc were found to be stable against dissolution in Ca(NO3)2 solution (up to 50 mM)
      because of the formation of strong surface complexes between U or Tc and Al
      oxyhydroxides. This research concludes that as long as a relatively high pH (> 5)
      and a low carbonate concentration are maintained, both U and Tc can be
      effectively immobilized under given site-specific conditions.

PMID- 19848171
TI  - Effect of fly ash on catalytic removal of gaseous dioxins over V2O5-WO3 catalyst
      of a sinter plant.
AB  - A PCDD/F(polychlorinated dibenzo-p-dioxin and dibenzofuran)-containing gas stream
      generating system was developed to investigate the efficiency and effectiveness
      of V2O5-WO3 catalyst for PCDD/F destruction. Catalytic decomposition of PCDD/Fs
      (simulated gas streams) was evaluated with lab-scale pelletized and plate-type
      catalyst based on V2O5-WO3/TiO2 at controlled temperature, space velocity, and
      inlet PCDD/F concentration. Due to the lower porosity of the pelletized catalyst
      PCDD/F destruction efficiencies reach 72.9-83.2% for different levels of inlet
      PCDD/F concentrations (1.08-3.04 ng-TEQ/Nm3) of the gas stream (space velocity:
      5000 h(-1)). As the surface area is increased from 287 m2/m3 (plate-type A) to
      550 m2/m3 (plate-type B), the PCDD/F destruction achieved with plate-type
      catalyst increases from 76.0% to 85.3% at 320 degrees C (space velocity: 5000 h(
      1)). In addition, the results of pilot-scale experiment (real flue gases of a
      sinter plant) indicate that relatively lower PCDD/F destruction efficiencies
      (62.1-65.7%) were achieved with the plate-type B catalyst as the solid-phase
      PCDD/F and fly ash passed through the reactor (space velocity: 5000 h(-1)).
      Overall, the lab-scale and pilot-scale experiments indicate that PCDD/F
      destructions achieved with pelletized and plate-type catalysts strongly depend on
      the operating temperature of the catalyst. The results also indicate that the
      presence of fly ash the lowers PCDD/F destruction due to significant PCDD/F
      formation via de novo synthesis at 320 degrees C.

PMID- 19848172
TI  - Evaluating aggregation of gold nanoparticles and humic substances using
      fluorescence spectroscopy.
AB  - The fate and transport of diagnostic gold nanoparticles in surface waters would
      significantly depend on their interactions with humic substances, which are
      ubiquitously found in natural aquatic systems. The current study employs UV
      visible absorbance and fluorescence spectroscopy to investigate the interactions
      of commercial humic acid (HA) with gold nanoparticles having a core size of 5 nm
      and coated with two different stabilizers, beta-D-glucose and citrate. Humic
      substances (HS) are fluorescent in nature, providing a unique probe of nanometer
      scale morphological changes for interactions between these natural
      polyelectrolytes and water-soluble gold nanoparticles. Quenching of fluorescence
      intensity was observed with beta-D-glucose-coated gold nanoparticles, whereas an
      enhancement effect was noticed with the citrate-coated particles when mixed with
      HA having concentrations of 2 and 8 ppm (surface waters typically may contain
      approximately 10 ppm HS). Examining the quenching and enhancement of fluorescence
      provides insight into the structural changes taking place at the coated gold
      nanoparticle-HA interface. The quenching behavior suggested ligand exchange due
      to nanometer-scale contact between the HA and beta-D-glucose-coated gold
      nanoparticles, whereas the enhancement effect with citrate particles would
      indicate overcoating, leading to increased transfer distances for fluorescence
      resonance energy transfer.

PMID- 19848173
TI  - Origin of hydroxylated brominated diphenyl ethers: natural compounds or man-made
      flame retardants?
AB  - Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants.
      The structurally related hydroxylated PBDEs (OH-PBDEs) and methoxylated PBDEs
      (MeO-PBDEs) occur in precipitation, surface water, wildlife, and humans. The
      formation of OH-PBDEs in wildlife and humans is of considerable concern due to
      their greater toxicities relative to PBDEs and MeO-PBDEs. Research to date
      suggests that OH-PBDEs are formed by hydroxylation of PBDEs, and MeO-PBDEs are
      then formed by methylation of the OH-PBDEs. Here we show significant metabolic
      production of OH-PBDEs from MeO-PBDEs while hydroxylation of synthetic PBDEs to
      OH-PBDEs was negligible. Concentrations of PBDEs, OH-PBDEs, and MeO-PBDEs were
      analyzed in tuna, albatross, and polar bears collected from marine environments
      worldwide, and we found a closer relationship between OH-PBDEs and MeO-PBDEs than
      had been previously reported. Furthermore, for the first time the metabolic
      relationships between PBDEs, OH-PBDEs, and MeO-PBDEs were elucidated in vitro
      using rainbow trout, chicken, and rat microsomes. We propose the production of OH
      PBDEs from naturally occurring MeO-PBDEs as a previously unidentified mechanism
      that could be an important contributor for the occurrence of OH-PBDEs found in
      wildlife from remote areas. Our results suggest that risk assessment paradigms
      for PBDEs and their metabolites need reevaluation and that human exposure to MeO
      PBDEs that occur naturally in marine organisms should be considered.

PMID- 19848174
TI  - Perinatal exposure to perchlorate. thiocyanate, and nitrate in New Jersey mothers
      and newborns.
AB  - Perchlorate is a commonly occurring environmental toxicant that may be
      transported across the placental barrier by the sodium-iodide symporter (NIS),
      possibly resulting in both increased perchlorate exposure and decreased iodide
      uptake by the fetus. Therefore, we measured levels of three physiologically
      relevant NIS-inhibitors (perchlorate, nitrate, and thiocyanate) and iodide in
      maternal and fetal fluids collected during cesarean-section surgeries on 150 U.S.
      women. Geometric means of perchlorate, thiocyanate, and nitrate levels in
      maternal urine (2.90, 947, and 47900 microg/L, respectively) were similar to
      previously published results, while urinary iodide levels (1420 microg/L) were
      significantly higher (p < 0.0001), likely because of prevalent prenatal vitamin
      use in the study population (74%). Thiocyanate levels were higher in the maternal
      serum, cord serum, and amniotic fluid of smokers compared to women with
      environmental tobacco smoke exposure and nonsmokers (p-values of 0.0006, 0.0011,
      and 0.0026, respectively). Perchlorate was detected in most samples: urine
      (100%), maternal serum (94%), cord serum (67%), and amniotic fluid (97%).
      Maternal urinary perchlorate levels were positively correlated with perchlorate
      levels in amniotic fluid (r = 0.57), indicating that maternal urine perchlorate
      is an effective biomarker of fetal perchlorate exposure. Maternal serum
      perchlorate was generally higher than cord serum perchlorate (median ratio 2.4:1
      for paired samples), and maternal urine perchlorate was always higher than fetal
      amniotic fluid perchlorate levels (mean ratio 22:1); conversely, iodide levels
      were typically higher in fetal fluids compared to maternal fluids. We found no
      evidence of either disproportionate perchlorate accumulation or lack of iodide in
      the fetal compartment. In this panel of healthy infants, we found no association
      between cord blood levels of these anions and newborn weight length, and head
      circumference.

PMID- 19848175
TI  - Lipid peroxidation induced by expandable clay minerals.
AB  - Small-sized environmental particles such as 2:1 phyllosilicates induce oxidative
      stress, a primary indicator of cell damage and toxicity. Herein, potential
      hazards of clay particle uptake are addressed. This paper reports that the
      content and distribution of structural Fe influence the ability of expandable
      clay minerals to induce lipid peroxidation (LP), a major indicator of oxidative
      stress, in biological matrices. Three smectite clays, hectorite (SHCa-1) and two
      nontronites (NAu-1) and (NAu-2) containing varying total content and coordination
      environment of structural Fe, were selected. Screening and monitoring of LP was
      conducted using a thiobarbituric acid reactive substances (TBARS) assay. The
      higher content of TBARS in nontronites than that in SHCa-1 suspensions was
      explained because structural Fe contributes to LP. The observed lack of
      correlation between TBARS content and the extent of Fe dissolution indicated that
      the formation of TBARS is surface controlled. Results showing a high TBARS
      content in SHCa-1 but not in nontronite supematant solutions was explained
      because the former contains distinct, soluble chemical component(s) that could
      (i) induce LP by its (their) own right and (ii) whose chemical affinity for
      organic ligands used as inhibitors is weak. Clays serve as stronger inductors
      than 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) but are much weaker
      than FeSO4. The outcome of this work shows that LP is clay surface-controlled and
      dependent on clay structural composition.

PMID- 19848176
TI  - Fungicide risk assessment for aquatic ecosystems: importance of interspecific
      variation, toxic mode of action, and exposure regime.
AB  - The risk assessment of fungicides in Europe uses information from ecotoxicity
      studies performed on vertebrates, invertebrates, and primary producers, but not
      nontarget fungi. But which toxicity data should be used to assess risk and how
      important are modes of action and exposure regimes? A data set was compiled
      comprising acute single-species toxicity data for 42 fungicides, semifield data
      for 12 fungicides, and covering seven toxic modes of action and different
      exposure regimes. Most fungicides were general biocides and data from all
      taxonomic groups were used to construct species sensitivity distributions (SSDs)
      and assess risk. The derived lower-limit HC5 values and HCl values were always
      protective of adverse ecological effects in semifield studies and HC5 values were
      protective for at least 3 of the fungicides. Expanding the analysis to include
      insecticides and herbicides, the following threshold values, derived from SSDs
      based on the most sensitive taxonomic group, are proposed to protect against
      adverse ecological effects from pesticide exposure: (i) the HC5 can be used for
      short-term exposures; (ii) the HC5 divided by 1.5 can be used for medium-term
      exposures; (iii) either the HCl or the HC5 divided by 3 can be used for long-term
      exposures.

PMID- 19848177
TI  - Carbon sequestration potential of extensive green roofs.
AB  - Two studies were conducted with the objective of quantifying the carbon storage
      potential of extensive green roofs. The first was performed on eight roofs in
      Michigan and four roofs in Maryland, ranging from 1 to 6 years in age. All 12
      green roofs were composed primarily of Sedum species, and substrate depths ranged
      from 2.5 to 12.7 cm. Aboveground plant material was harvested in the fall of
      2006. On average, these roofs stored 162 g C x m(-2) in aboveground biomass. The
      second study was conducted on a roof in East Lansing, MI. Twenty plots were
      established on 21 April 2007 with a substrate depth of 6.0 cm. In addition to a
      substrate only control, the other plots were sown with a single species of Sedum
      (S. acre, S. album, S. kamtshaticum, or S. spurium). Species and substrate depth
      represent typical extensive green roofs in the United States. Plant material and
      substrate were harvested seven times across two growing seasons. Results at the
      end of the second year showed that aboveground plant material storage varied by
      species, ranging from 64 g C x m(-2) (S. acre) to 239 g C x m(-2) (S. album),
      with an average of 168 g C x m(-2). Belowground biomass ranged from 37 g C x m(
      2) (S. acre) to 185 g C x m(-2) (S. kamtschaticum) and averaged 107 g C x m(-2).
      Substrate carbon content averaged 913 g C x m(-2), with no species effect, which
      represents a sequestration rate of 100 g C x m(-2) over the 2 years of this
      study. The entire extensive green roof system sequestered 375 g C x m(-2) in
      above- and belowground biomass and substrate organic matter.

PMID- 19848178
TI  - Effects of substrate diffusion and anode potential on kinetic parameters for
      anode-respiring bacteria.
AB  - The substrate-utilization rate of anode-respiring bacteria (ARB) directly
      correlates to the current density, one of the main factors in a microbial
      electrolysis/fuel cell. This study first evaluates the effects of donor-substrate
      diffusion and anode potential on the estimation of the half-maximum-rate
      concentration (K(s)) and the maximum specific substrate-utilization rate (q(max))
      of a mixed culture biofilm in a microbial electrolysis cell oxidizing acetate.
      The intrinsic K(s) value is 119 g COD/m3, substrate diffusion has a significant
      impact on K(s) estimation, and the effect of the anode potential on K(s) is
      small. The intrinsic q(max) value is 22.3 g COD/g VS-d for an assumed biomass
      density of 50,000 g VS/m3 (q(max)X(f) = 1120 kg COD/m3-d). The maximum specific
      growth rate (micro(max)) is 3.2/d which is substantially faster than for acetate
      utilizing methanogens and homoacetogens. Although the anode potential affects
      q(max), substrate diffusion has a negligible effect. The measured half-saturation
      anode potential (E(KA)) is very negative, -0.448 V (vs Ag/AgCl), and this low
      value minimizes anode-potential limitation on the current density and the
      substrate-utilization rate. Thus, the ARB selected in our biofilm anode were
      relatively fast growers able to take advantage of their low E(KA) value (-0.448
      V).

PMID- 19848179
TI  - Model for cradle-to-gate life cycle assessment of clinker production.
AB  - A model for input- and technology-dependent cradle-to-gate life cycle assessments
      (LCA)was constructed to quantify emissions and resource consumption of various
      clinker production options. The model was compiled using data of more than 100
      clinker production lines and complemented with literature data and best judgment
      from experts. It can be applied by the cement industry for the selection of
      alternative fuels and raw materials (AFR) and by authorities for decision-support
      regarding the permission of waste co-processing in cement kilns. In the field of
      sustainable construction, the model can be used to compare clinker production
      options. Two case studies are presented. First, co-processing of four different
      types of waste is analyzed at a modern precalciner kiln system. Second, clinker
      production is compared between five kiln systems. Results show that the use of
      waste (tires, prepared industrial waste, dried sewage sludge, blast furnace slag)
      led to reduced greenhouse gas emissions, decreased resource consumption, and
      mostly to reduced aggregated environmental impacts. Regarding the different kiln
      systems, the environmental impact generally increased with decreasing energy
      efficiency.

PMID- 19848180
TI  - Comment on "Halogenated contaminants in farmed salmon, trout, tilapia, pangasius,
      and shrimp".

PMID- 19848181
TI  - Comment on "Atmospheric particulate matter pollution during the 2008 Beijing
      Olympics".

PMID- 19848182
TI  - Comment on "Atmospheric particulate matter pollution during the 2008 Beijing
      Olympics".

PMID- 19848183
TI  - Bringing abundance into environmental politics: Constructing a Zionist network of
      water abundance, immigration, and colonization.
AB  - For more than five decades, resource scarcity has been the lead story in debates
      over environmental politics. More importantly, and whenever environmental
      politics implies conflict, resource scarcity is constructed as the culprit.
      Abundance of resources, if at all visited in the literature, holds less
      importance. Resource abundance is seen, at best, as the other side of scarcity-
      maybe the successful conclusion of multiple interventions that may turn scarcity
      into abundance. This paper reinstates abundance as a politico-environmental
      category in its own right. Rather than relegating abundance to a second-order
      environmental actor that matters only on occasion, this paper foregrounds it as a
      crucial element in modern environmental politics. On the substantive level, and
      using insights from science and technology studies, especially a slightly
      modified actor-network framework, I describe the emergence and consolidation of a
      Zionist network of abundance, immigration, and colonization in Palestine between
      1918 and 1948. The essential argument here is that water abundance was
      constructed as fact, and became a political rallying point around which a techno
      political network emerged that included a great number of elements. To name just
      a few, the following were enrolled in the service of such a network: geologists,
      geophysicists, Zionist settlement experts, Zionist organizations, political and
      technical categories of all sorts, Palestinians as the negated others,
      Palestinian revolts in search of political rights, the British Mandate
      authorities, the hydrological system of Palestine, and the absorptive capacity of
      Palestine, among others. The point was to successfully articulate these disparate
      elements into a network that seeks opening Palestine for Jewish immigration,
      redefining Palestinian geography and history through Judeo-Christian Biblical
      narratives, and, in the process, de-legitimizing political Palestinian presence
      in historic Palestine.

PMID- 19848184
TI  - Pharmacovigilance and post-black market surveillance.
AB  - Pharmacovigilance can be defined as a set of practices aiming at the detection,
      understanding and assessment of risks related to the use of drugs in a
      population, and the prevention of consequential adverse effects. In a narrower
      sense, the term refers exclusively to postmarket surveillance. This paper briefly
      outlines how pharmacovigilance has come to play a central role in the regulation
      of novel pharmaceuticals. However, the focus of the text is on mechanisms
      emerging in an experimental drug scene that aim at dealing with the risks posed
      by 'designer drugs' newly introduced to the black market. This discussion of
      pharmacovigilance and 'post-black market surveillance' is situated in the broader
      context of the more recent dissemination of vigilance as a key element of
      government in a world too complex for legal and disciplinary measures alone.

PMID- 19848185
TI  - Ethanol versus gasoline: the contestation and closure of a socio-technical system
      in the USA.
AB  - A variety of forces aligned at the turn of the last century to make ethyl alcohol
      -what is today known as ethanol--inefficient and uneconomical as a fuel
      alternative. Rather than a case of inevitable technological unfolding, the
      transition from King Coal to Big Oil was a sociologically contingent event. As a
      controversy study, this paper seeks to avoid the reductionist tendencies of past
      historical analyses of fuel. The author also seeks to redress a fundamental gap
      within the STS literature on the subject of automobile/fuel socio-technical
      systems, where the story of ethyl alcohol remains conspicuously absent. Among
      studies that examine how/why the automobile became locked in, little is said
      about ethyl alcohol, even though, as this paper details, it remained part of the
      fuel landscape well into the 20th century. The paper begins with an overview of
      the landscape developments of fuel during the later decades of the 19th century.
      Attention then turns to examining the various factors that went into shaping the
      automobile/fuel socio-technical system within the US during the first half of the
      20th century.

PMID- 19848186
TI  - The ambiguities of disciplinary professionalization: The state and cultural
      dynamics of Canadian inter-war anthropology.
AB  - The professionalization of Canadian anthropology in the first half of the
      twentieth century was tied closely to the matrix of the federal state, first
      though the Anthropology Division of the Geological Survey of Canada and then the
      National Museum. State anthropologists occupied an ambiguous professional status
      as both civil servants and anthropologists committed to the methodological and
      disciplinary imperatives of modern social science but bounded and guided by the
      operation of the civil service. Their position within the state served to both
      advance disciplinary development but also compromised disciplinary autonomy. To
      address the boundaries the state imposed on its support for anthropology, state
      anthropologists cultivated cultural, intellectual, and commercially-oriented
      networks that served to sustain new developments in their field, particularly in
      folklore. This essay examines these dynamics and suggests that anthropology's
      disciplinary development did not create a disjuncture between professionalized
      scholarship and civil society.

PMID- 19848187
TI  - [Defense of the nation contrary to prosperity of the discipline: military
      engagement and institutionalization of psychology in Canada].
AB  - This article contributes to our knowledge about the rise of the social and human
      sciences through an examination of military uses of psychology in Canada and this
      field sensibility to external demand. The national crisis caused by World War II
      and the Cold War were perceived by psychologists as sizeable opportunities to
      promote psychological expertise outside academe and to strengthen the social
      authority of their discipline and profession. By the way of military patronage
      and psychological contribution to National defense, psychological expertise then
      gained new symbolic and material resources. Does it mean that this field
      exogeneity undermine its disciplinary practices or knowledge production? It is
      said that this is an empirical question that bears no univocal answers.

PMID- 19848188
TI  - [Elementary, my dear Watson!].

PMID- 19848189
TI  - [Bioproduction of pharmaceutical proteins: review and perspectives].
AB  - The increase in importance of the biopharmaceutical market generates enormous
      needs in production of therapeutic molecules. The world capacities of production,
      mainly therapeutic proteins, impossible to obtain by chemical synthesis, are at
      present insufficient. Besides the economic aspects in set, play, the question of
      the technologies used to produce these molecules is important: the tried(felt)
      technologies (bacteria, yeasts, cells of mammals), used for a long time rather
      widely remain expensive, or see their limited field of application; the
      innovative technologies (avian cells, animal and plant transgenic, among others),
      as for them, again have to show their ability.

PMID- 19848190
TI  - [Scientific horizon and industrial stake in the biosynthesis of nucleic acids].
AB  - Nucleic acids offer an ample structural and functional plasticity enabling their
      industrial production and chemical diversification for therapeutic purposes as
      well as the establishment in vivo and in vitro of informational processes that
      did not spontaneously occur during evolution.

PMID- 19848192
TI  - "If there is nothing beyond the organic..." Heredity and culture at the
      boundaries of anthropology in the work of Alfred L. Kroeber.

PMID- 19848191
TI  - [Embryonic stem cells in pharmacology].
AB  - Because of their self-renewal and pluripotency properties, human embryonic stem
      cells (hES) receive a marked attention from scientists and clinicians for
      regenerative medicine. The most recent application of hES cells may however
      reside in their use as a tool in drug development. The currently available
      cellular models for preclinical testing consist in primary and immortalized cells
      that display limitations in terms of available amount and likeliness to their in
      vivo counterparts, respectively. hES cells have the potential to revolutionize
      drug discovery by providing a physiological model for any human cell type in the
      desired amount for the earliest steps of drug development, notably for
      pharmacological, metabolic and toxicity evaluation. This new generation of model
      may contribute to reduce, refine or replace animal testing and decrease drug
      attrition.

PMID- 19848193
TI  - [Constructing climate. From classical climatology to modern climate research].
AB  - Both climate researchers and historians of climate science have conceived climate
      as a stable and well defined category. This article argues that such a conception
      is flawed. In the course of the 19th and 20th century the very concept of climate
      changed considerably. Scientists came up with different definitions and concepts
      of climate, which implied different understandings, interests, and research
      approaches. Understanding climate shifted from a timeless, spatial concept at the
      end of the 19th century to a spaceless, temporal concept at the end of the 20th.
      Climatologists in the 19th and early 20th centuries considered climate as a set
      of atmospheric characteristics associated with specific places or regions. In
      this context, while the weather was subject to change, climate remained largely
      stable. Of particular interest was the impact of climate on human beings and the
      environment. In modern climate research at the close of the 20th century, the
      concept of climate lost its temporal stability. Instead, climate change has
      become a core feature of the understanding of climate and a focus of research
      interests. Climate has also lost its immediate association with specific
      geographical places and become global. The interest is now focused on the impact
      of human beings on climate. The paper attempts to investigate these conceptual
      shifts and their origins and impacts in order to provide a more comprehensive
      perspective on the history of climate research.

PMID- 19848194
TI  - [Clinical application of polypill and the research and development of Chinese
      patent medicine].

PMID- 19848195
TI  - [Clinical study on effect of qingxuan tiaoya recipe in treating menopausal women
      with hypertension].
AB  - OBJECTIVE: To investigate the effect and mechanism of Qingxuan Tiaoya Recipe
      (QXTYR) on depressing blood pressure in menopausal women with hypertension.
      METHODS: Patients were randomly assigned to two groups, the 44 patients in the
      test group were administered with perindopril tablet and QXTYR granule, while the
      43 in the control group were administered with the same program, but a simulator
      of QXTYR was used to replace for the real one. The treatment course for them all
      was 2 months. Before and after treatment, the ambulatory blood pressure (ABMP),
      heart rate, related clinical symptoms, blood lipids, serum estradiol (E2), high
      sensitivity C-reactive protein ( Hs-CRP), homocysteine (HCY) and angiotensin II
      (Ang II) were measured. RESULTS: The treatment in the test group showed an effect
      better than that in the control group in terms of reducing blood pressure
      variability and night-time blood pressure decrease rate (P <0.05), with the total
      effective rate and markedly effective rate in lowering blood pressure superior to
      the control group (P<0.05), alleviating symptoms as headache, soreness and
      weakness of the waist and knees, and insomnia (P <0.05), and decreasing levels of
      heart rate, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C),
      Hs-CRP and Ang II (P <0.05), The plasma level of endogenous E2 was elevated after
      treatment in the test group (P< 0.05), but showed no statistical difference in
      the control group. CONCLUSIONS: QXTYR shows favorable effect in depressing blood
      pressure of menopausal women with hypertension, it can reduce blood pressure
      variability, improve the symptoms of the menopause syndrome, blood lipid
      metabolism and plasma levels of Hs-CRP, E2, and Ang II in patients, suggesting
      that its mechanism may be related to the functional regulation of sympathetic
      vagus nerve and neuro-endocrine-immune system, and also the inhibition on the
      circulatory renin-angiotensin-aldosterone system activity.

PMID- 19848196
TI  - [Efficacy of shenfu injection as adjuvant therapy in treating patients of
      ischemic cardiomyopathy with heart insufficiency].
AB  - OBJECTIVE: To evaluate the clinical efficacy of Shenfu Injection (SFI), as a
      adjuvant therapy, in treating patients of ischemic cardiomyopathy with heart
      insufficiency (ICP-HI). METHODS: One hundred patients of ICP-HF were equally
      randomized into two groups, the SFI group and the control group. All received the
      conventional treatment, but to patients in the SFI group SFI was given
      additionally via intravenous injection, 60 mL once a day, 10 days each month, the
      treatment course was 6 months. Changes of cardial functional grading, 6-min
      walking distance, echocardiographic indices, plasma N terminal pro-brain
      natriuretic peptide (pro-BNP) level were observed before and after treatment, and
      the occurrence of major adverse cardiovascular events (MACE) and mortality in
      patients were observed as well. RESULTS: As compared with the conventional
      treatment alone, additional application of SFI showed a more significant efficacy
      in improving NYHA functional grade and 6-min walking distance, reducing the
      diameters of left ventricular at end diastole and systole, increasing left
      ventricular ejection fraction, and decreasing plasma N terminal pro-BNP level (P
      <0.05). The occurrence of MACE and the mortality in the SFI group were
      significantly lower than those in the control group respectively (P <0.05).
      CONCLUSIONS: Based on the conventional treatment, the adjuvant therapy of SFI
      could improve the cardiac function, improve the quality of life, ameliorate
      ventricular reconstruction, and decrease the occurrence of cardiovascular events
      in patients of ICP-HI.

PMID- 19848197
TI  - [Influence of apolipoprotein E gene polymorphism on the lipid regulation by
      xuezhikang capsule].
AB  - OBJECTIVE: To explore the influence of apolipoprotein E (ApoE) gene polymorphism
      on the lipid metabolism regulatory effect of Xuezhikang Capsule (XZKC). METHODS:
      ApoE polymorphism of 74 patients with hyperlipidemia was detected by gene
      sequencing method, and their plasma levels of total cholesterol (TC),
      triglyceride (TG), high- and low-density lipoprotein cholesterol (HDL-C and LDL
      C) were determined before and after they received a 6-week treatment of XZKC, for
      analyzing the relationship between ApoE gene polymorphism and the changes of
      various blood lipids associated indices. RESULTS: The effect of XZKC on reducing
      TG in the epsilon2 allele (E2/E2 and E2/E3 genotypes) was higher than that in the
      E3/E3 genotypes and epsilon4 allele (E3/E4 and E4/E4 genotypes), while on
      increasing HDL-C, it showed more effect in the epsilon4 allele (E3/E4 and E4/E4
      genotypes) than that in the epsilon2 allele (E2/E2 and E2/E3 genotypes) and E3/E3
      genotypes. CONCLUSION: Patients' ApoE gene polymorphism could influence the lipid
      regulatory effect of XZKC, embodying mainly by raising HDL-C and reducing TG in
      patients with different ApoE genotypes to different extents.

PMID- 19848198
TI  - [Effect of danhong injection on platelet activation and inflammatory factors in
      patients of acute coronary syndrome after intervention therapy].
AB  - OBJECTIVE: To explore the effect of Danhong Injection (DHI) on platelet
      activation and inflammatory factors in patients of acute coronary syndrome (ACS)
      after intervention therapy. METHODS: One hundred ACS patients were randomly
      assigned to the DHI group and the control group equally. Both were treated with
      the conventional treatment, including aspirin, clopidogrel, beta-receptor
      blocker, angiotensin converting enzyme inhibitor, etc. for 2 weeks after
      percutaneous coronary intervention (PCI), and to the patients in the DHI group,
      intravenous dripping of DHI was given simultaneously. Fasting venous blood of
      patients were collected before PCI and on the next morning of PCI to determine
      the platelet activation indices, expression of CD62p and receptor complex of
      glucose protein (GP) II b/III a by flow cytometry; plasma fibrinogen C (FIB-C) by
      scattering turbidimetry, and serum high-sensitivity C-reactive protein (hs-CRP)
      with emulsoid immuno-enhancing turbidimetric test kit. The outcomes were compared
      with those determined in 40 healthy persons for control. RESULTS: Serum levels of
      CD62p, GP II b/III a, FIB-C and hs-CRP in ACS patients were significantly higher
      than those in the healthy control (all P<0.01), and those were significantly
      higher after PCI than before PCI (P <0.05 or P<0.01). After being treated for 2
      weeks, the 4 platelet activation indices were lowered to different extent in both
      groups, but the lowering in the DHI group was more significant than that in the
      control group (P<0.05). CONCLUSION: DHI can inhibit the platelet activation and
      inflammatory reaction in ACS patients after PCI.

PMID- 19848199
TI  - [Effect of buxu huayu qutan decoction on anti-oxidative capacity in aged patients
      with stable angina pectoris of coronary heart disease].
AB  - OBJECTIVE: To investigate the acting mechanism of Buxu Huayu Qutan Decoction
      (BHQD) for impacting the anti-oxidative capacity in aged patients with stable
      angina pectoris of coronary heart disease (AP-CHD). METHODS: Forty patients of AP
      CHD, Chinese medicine diagnosed as Xiong-bi, were equally assigned to the
      treatment group and the control group. Superoxide dismutase (SOD) activity and
      lipid peroxide (LPO) contents in blood, and mRNA expression of manganese
      containing superoxide dismutase (MnSOD) in peripheral mononuclear cells were
      determined before and after treatment by biochemical and molecular biologic
      techniques. RESULTS: No significant change of plasma SOD and LPO was found in the
      control group after treatment (P >0.05), while the plasma SOD activity increased
      and LPO content lowered in the treatment group significantly (P<0.01). Moreover,
      mRNA expression of MnSOD in the treatment group after treatment was obviously
      higher than that in the control group (P <0.01). CONCLUSIONS: The acting
      mechanism of BHQD for AP-CHD treatment might partially due to its effects in
      inducing gene expression of MnSOD in mononuclear cells, enhancing SOD activity,
      decreasing LPO content, maintaining oxidation/antioxidation equilibrium in
      myocardial cells, blocking the chain reaction of lipid peroxidation, intervening
      the production and enhancing the scavenging of oxygen free radicals.

PMID- 19848200
TI  - [A retrospective study on type 2 diabetes mellitus treated with integrated
      Chinese and Western medicine].
AB  - OBJECTIVE: To compare the therapeutic efficacy and cost-efficacy of different
      treatment methods for treatment of type 2 diabetes mellitus (T2DM). METHODS:
      Based on the electronic inpatient clinical information systems, clinical
      materials of T2DM patients were collected and assigned according to the
      therapeutic method used, to the groups of Western medicinal (WM) treatment (A),
      WM combined Chinese drug injection treatment (B) and the WM combined Chinese
      decoction or patent drugs treatment (C). Depending on the data of symptom scores,
      blood sugar and blood lipids, etc., the efficacy of different treatments were
      analyzed in terms of improving symptoms, elevating the quality of life (QOL),
      controlling blood sugar, reducing dosage of insulin used and diminishing economic
      expense, with the enumeration data analyzed by chi2 test and the measurement data
      by ANOVA. RESULTS: Treatment C showed a better efficacy than the other two in
      improving symptoms, elevating QOL, controlling blood sugar, reducing dose of
      insulin used and lightening the financial burden (P < 0.05). CONCLUSION:
      Selective use of Chinese drugs depending on syndrome differentiation is
      recommended during combined application of Chinese and Western medicine; and the
      Chinese medicine injection is not advised as the first scheme for treatment of
      T2DM.

PMID- 19848201
TI  - [Effect of shenmai injection on patients suffering from malnutrition-inflammation
      complex syndrome during the maintenance hemodialysis].
AB  - OBJECTIVE: To investigate the effect of Shenmai Injection (SMI) on patients
      undergoing maintenance hemodialysis (MHD) suffered from malnutrition-inflammation
      complex syndrome (MICS). METHODS: Forty patients undergoing MHD were randomly
      allocated into two groups, the SMI group and the control group, 20 in each group.
      They were treated for three months. Blood levels of albumin (Alb), high
      sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6) and interleukin
      1beta (IL-1beta) as well as stomatologic parameters were measured before and
      after treatment. Meantime, the modified subjective global analysis of nutrition
      (SGAN) was used to assess patients' nutritional status, and the quantitative
      scoring system was adopted to get the malnutrition score (MS). RESULTS: In the
      SMI group after treatment, levels of MS, hs-CRP, IL-6 and IL-1beta were lowered,
      levels of Alb, body weight, and SSF were increased significantly (P <0.05 or P
      <0.01); as compared with those in the control group, MS, hs-CRP and IL-6 were
      lower, while SSF and Alb were higher (P<0.05 or P< 0.01). Levels of IL-6 and IL
      1beta, either in the SMI group or in the control group, were all higher than
      normal range (P<0.05). Correlation analysis showed significant correlation
      presented between MS value with levels of Alb (P<0.01) and IL-6 (P <0.05), also
      between IL-6 and Alb (P<0.05). CONCLUSION: SMI can reduce the blood levels of hs
      CRP, IL-6 and IL-1beta in patients undergoing MHD, improve their nutritional
      indices, suggesting that it could alleviate the MICS in these patients.

PMID- 19848202
TI  - [Effect of puerarin on liver injury in KKAy mice with type 2 diabetes mellitus].
AB  - OBJECTIVE: To study the possible pathogenic mechanism of liver injury in type 2
      diabetes mellitus (T2DM) and the intervening effect of puerarin on it. METHODS:
      Mice with T2DM (KKAy) were randomly divided into two groups, the model group and
      the puerarin group. And the C57BL/J mice of the same age were set up as normal
      controls. They were sacrificed at 28 weeks old for observing serum fasting blood
      glucose (FBG), triglyceride (TG), total cholesterol (TC), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) by automatic
      biochemistry; liver cell apoptosis by flow cytometry; pathomorphology by electron
      microscope; and mRNA expressions of bcl-2 and bax genes by RT-PCR; as well as the
      activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na(+)
      K(+)-ATPase; and content of malondialdehyde (MDA) in liver tissue by
      spectrophotometer. RESULTS: In KKAy mice, blood levels of FBG, TG, TC, ALT, AST
      and liver cell apoptosis rate were higher; the bax mRNA expression was higher and
      bcl-2 mRNA was lower markedly; the activities of SOD, GSH-Px, Na(+)-K(+)-ATPase
      in liver tissue were lower, and MDA content was higher than those in the normal
      control significantly (all P <0.01). Besides, mitochondria swelling and damage
      were found in liver tissue. While in the puerarin group after treatment, all the
      above-mentioned changes were alleviated to some extent. CONCLUSIONS: Obvious
      liver injury emerges in KKAy mice. Puerarin shows a protective effect on the T2DM
      caused oxidative damage by way of up-regulating bcl-2 to inhibit oxidative
      stress, and improving the energy metabolic dysfunction in liver of mice.

PMID- 19848203
TI  - [Effect of total alkaloids of Rubus alceaefolius poiron on gene expressions of
      CYP2E1 and CYP3A1 in rats with acute liver injury].
AB  - OBJECTIVE: To explore the effects of total alkaloids of Rubus alceaefolius Poiron
      (RAP) on gene expressions of drug-metabolic enzymes, CYP2E1 and CYP3A1 in liver.
      METHODS: Sixty SD rats were randomly divided into six groups (10 rats in each),
      the blank control group, the model control group, the bifendate group and the
      three RAP treated groups treated respectively with low-, middle- and high-dose of
      RAP. The model of acute hepatic injury was established with intra-peritoneal
      injection of carbon tetrachloride. Serum levels of alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST), and severity of hepatic tissue injury were
      measured, and the mRNA expressions of CYP2E1 and CYP3A1 in liver tissue were
      detected by RT-PCR. RESULTS: As compared with the model group, serum levels of
      ALT and AST were significantly lower in the high- and middle-dose ARP group (P
      <0.01), but in the low-dose group, only ALT was significantly lower (P<0.01); the
      severity of liver injury was milder in the RAP groups (P<0.01); and both CYP2E1
      and CYP3A1 mRNA expressions in liver were significantly lower in the bifendate
      and all RAP treated groups (P<0.01 or P<0.05). CONCLUSION: RAP could
      significantly reduce the ALT and AST levels, protect liver cells from injury, and
      inhibit the mRNA expressions of CYP2E1 and CYP3A1 in liver tissue.

PMID- 19848204
TI  - [Feature of airway inflammation in asthmatic rats complicated with chronic
      obstructive pulmonary disease and effect of Chinese herbs for reinforcing Shen
      and supplementing qi on it].
AB  - OBJECTIVE: To observe the airway inflammatory change in asthmatic rats
      complicated with chronic obstructive pulmonary disease (COPD) and to assess the
      intervention effects of Chinese herbs for reinforcing Shen and supplementing qi
      (CH) on it. METHODS: Eighty-four Norway rats were randomized into 7 groups, the
      normal control group (A), the COPD model group (B), the asthma model group (C),
      the combined COPD and the asthma model group (D), and the three CH treated groups
      (E, F and G, combined model rats administered by low-, moderate- and high- dose
      CH, respectively), 12 rats in each group. Changes of symptoms, pathologic changes
      of the lung tissue, airway reactivity, and serum levels of interleukin-4,
      interleukin-6, interleukin-8 (IL-4, IL-6, and IL-8) and interferon-gamma (IFN
      gamma) in rats were observed. RESULTS: Symptoms were alleviated in the three CH
      treated groups. Similar pathological features were shown in group B and D,
      showing inflammatory cell, mainly lymphocyte, infiltration in bronchial and lung
      tissues, with cilia denudation, partial alveolar wall rupture, alveolar cavity
      expansion, and accompanied with evident eosinophilic infiltration. These
      inflammatory exudation in group E-G was alleviated, while in group C, it
      developed showing a trend similar to that in group D. Airway resistance raised
      along with the concentration of Mch used. In group D, the serum level of IL-4 was
      higher than that in group B, and level of INF-gamma was lower than that in group
      A, B and C (all P <0.05). CH showed a lowering effect on serum levels of IL-4 and
      -8, and a dose-dependent rising effect on IFN-gamma. CONCLUSIONS: IL- 4
      significantly increased and INF-gamma decreased in rat model of combined COPD and
      asthma, its mechanism is similar to that of Th1/Th2 imbalance in asthma. Chinese
      herbs for reinforcing Shen and supplementing qi could improve the symptoms and
      inhibit the airway inflammation in the combined COPD and asthma model rats, its
      mechanism might be related with the alleviation of TH1/TH2 imbalance.

PMID- 19848205
TI  - [Effect of jieze no. 1 gel on vaginal levels of lactobacillus, glycogen and
      lactoferrin in mice].
AB  - OBJECTIVE: To evaluate the effect of Jieze No. 1 Gel (JZ1) on the inner
      environment of vagina through observing its influences on vaginal levels of
      lactobacillus, glycogen and lactoferrin in mice. METHODS: One hundred female
      Kunming mice were randomized into 5 groups, the blank control (BC) group, the
      blank gel (BG) group, and the three JZ1 treated groups. They were treated via
      vagina with saline, matrix gel, high (2 mg/microL), middle (1 mg/microL) and low
      (0.5 mg/microL) dose JZ1 respectively in volume of 20 microL, 72 h after being
      subcutaneously injected with physiological estradiol benzoate (E2) 2 microg. The
      24 h and 72 h living lactobacillus in vaginal lavage fluid cultures were counted,
      the content of glycogen and the expression of lactoferrin in vaginal tissue were
      measured. RESULTS: No significant difference was found between the BC group and
      the three JZ1 treated groups in terms of lactobacillus-CFU, glycogen content and
      lactoferrin expression, and these indices detected at 24 h were not different to
      those detected at 72 h in the groups treated with various doses of JZ1
      respectively (P > 0.05). CONCLUSION: Once application of JZ1 shows no effect on
      levels of lactobacillus, glycogen, and lactoferrin expression in the vagina of
      mice.

PMID- 19848206
TI  - [Effect of compound Chinese sour taste herbs on advanced glycation end products
      content and gene expression of their receptors in aorta of rats with type 2
      diabetes mellitus].
AB  - OBJECTIVE: To investigate the possible mechanism of compound Chinese sour taste
      herbs (CS) in preventing and ameliorating diabetic macroangiopathy by analyzing
      the effects of CS on the deposition of advanced glycation end products (AGEs) and
      gene expression of receptor for advanced glycation end products (RAGE) in the
      aorta tissue of rats with type 2 diabetes mellitus (T2DM). METHODS: Rat model of
      T2DM was established by peritoneal injection of streptozotocin (STZ) and high
      caloric diet feeding. Experimental SD rats were divided into the normal group,
      the model group, the aminoguanidine (AG) group, and the CS group. At the end of
      the 8th and 12th week, the fasting blood glucose (FBG) was measured by glucose
      oxidase method; content of AGEs and collagen in aorta detected by fluorescent
      method and gene expression of RAGE in aorta determined by Real-time PCR method.
      RESULTS: FBG, AGEs and collagen contents and RAGE expression in aorta of model
      rats were all higher than those in the normal control group (P <0.05), while all
      these indices were lower in the CS group than in the model group (P<0.05).
      CONCLUSION: CS could realize the goal for preventing and ameliorating diabetic
      macroangiopathy by way of suppressing the production of AGEs and down-regulating
      the gene expression of RAGE in aorta of T2DM rats.

PMID- 19848207
TI  - [Effect of wujia bugu recipe on intestinal calcium absorption in rats under
      simulated weightlessness manner].
AB  - OBJECTIVE: To investigate the intervention effect of Wujia Bugu Recipe (WBR,
      consisting of Radix Rehmanniae Praeparata, Radix Achyranthis bidentate, Radix
      Astragali, Radix Angelicae sinensis, acetolytic substance of Concha Ostreae) on
      the intestinal absorption of exogenous calcium in rats under simulated
      Weightlessness manner. METHODS: Twenty-one male Wistar rats were randomly divided
      into 3 groups, the blank group, the model group, and the tested group treated
      with WBR via gastric perfusion. Simulated weightlessness manner was formed by
      tail suspending after rats' entry into an one-week adaptation stage. And a
      definite dose of 41Ca tracer was given to each rat by gastric administration on
      the 11th day of the weightless stage. Their 72 h feces were collected for
      measuring ratio of 41Ca/40Ca by accelerator mass spectrometry (AMS), the total
      calcium in feces was determined by inductively coupled plasma-atomic emission
      spectroscopy (ICP-AES), the 41Ca feces content (FC) and intestinal absorption
      amount (AA), and then the calcium intestinal absorption ratio (AR) were analyzed
      and calculated. RESULTS: 41Ca/40Ca ratio and 41Ca FC were higher, 41Ca AA and AR
      were lower in the model group than those in the blank group, the differences
      between groups were significant (P <0.01); while in the tested group, the
      differences of all above-mentioned indices with those in the blank group were
      insignificant, although the 41Ca/40Ca ratio showed somewhat increased, yet the
      increment was less than that in the model group (P <0.05). CONCLUSION: Simulated
      weightlessness could lead to decrease of intestinal calcium absorption, which
      could be improved to some extent by Chinese herbal medicine.

PMID- 19848208
TI  - [Effect of bushen tongmai recipe on insulin resistance and ovulation dysfunction
      in PCOS rats accompanied with insulin resistance].
AB  - OBJECTIVE: To establish a rat model of polycystic ovarian syndrome accompanied
      with insulin resistance (PCOS-IR), and to observe the effects of Bushen Tongmai
      Recipe (BSTMR) on insulin resistance and ovulation dysfunction in the model.
      METHODS: Sodium prasterone sulfate at the daily dose of 9 mg/100 g was
      subcutaneously injected to female SD rats, 23-day old, for 20 days, and fed with
      high-fat forage for 80 days to establish the rat model of PCOS-IR. The model rats
      were randomized into the model group and the treated group administered with
      BSTMR. Besides, a group consisted of 15 healthy rats was set up as a normal
      control. Ovarian histological changes and ovulation condition in rats were
      examined with hematoxylin and eosin (HE) staining; fasting blood glucose (FBG)
      was determined by glucose oxidase method; serum levels of fasting insulin (FINS),
      serum testosterone (T), estradiol (E2), progesterone (P), follicle stimulating
      hormone (FSH) and luteotrophic hormone (LH) were detected by radioimmunoassay
      (RIA). RESULTS: Compared with the normal group, in the model group, the mean
      number of corpus luteum, ovulation rate, FSH level and insulin sensitive index
      (ISI) were lower significantly (P <0.01), and levels of FBG, FINS, T, E2 and LH
      were higher (P<0.05, P <0.01). Compared with the model group, in the treated
      group, the mean number of corpus luteum, ovulation rate, levels of FSH and ISI
      were higher, and levels of FINS, T and E, were lower (all P <0.01). CONCLUSION:
      Rat model of PCOS-IR could be established by sodium prasterone sulfate and high
      fat forage, and the insulin resistance and ovulation dysfunction in the model
      rats could be improved by BSTMR.

PMID- 19848209
TI  - [Effect of sanqidan granule in treating patients of type 2 diabetes mellitus
      complicated with hypertension].
AB  - OBJECTIVE: To evaluate the effect of treatment for tonifying qi, nourishing yin,
      activating blood circulation and removing stasis on insulin resistance (IR) in
      patients of type 2 diabetes mellitus (T2DM) complicated with hypertension.
      METHODS: Forty-five patients of T2DM with hypertension enrolled from authors'
      special clinics were equally randomized into two groups: the test group (20
      patients) and the control group (25 patients). Both groups received orally
      hypoglycemic drugs, such as glipizide sustained-release tablets, pioglitazone,
      and metformin, and antihypertensive drug as nifedipine sustained-release tablets
      as well. Additionally, Sanqidan Granules (SQD), a Chinese patent medicine was
      given to the test group. The course of treatment lasted for 8 weeks. The clinical
      efficacy of Chinese medicine syndromes, blood pressure, T2DM related indices and
      blood lipids in the two groups were observed. RESULTS: The effect in improving
      Chinese medicine syndromes in the test group was better than that in the control
      group significantly (P <0.05). After treatment, all the indices were examined,
      except FINS and TG were improved in the test group, showing significant
      difference as compared with those before treatment; while in the control group,
      significant difference was only shown in terms of fasting blood glucose (FBG),
      HbA1 c, systolic blood pressure (SBP) and HDL-C (P <0.01). Comparison between
      groups showed that the effect in the former was better than that in the latter
      group in terms of decreasing FBG, HbA1c, SBP and increasing of HDL-C (P <0.05),
      while a downward trend of ISI in the test group was shown but with no statistical
      significance (P = 0.230). CONCLUSIONS: SQD can relieve the clinical symptoms in
      patients of syndrome of qi-yin deficiency and inner blockage of blood stasis,
      increase the insulin sensitivity and reduce the IR in patients, so as to decrease
      their FBG, blood pressure and HbAlc. It also can increase HDL-C level, and lower
      TC and LDL-C levels, which is beneficial to anti-atherosclerosis.

PMID- 19848210
TI  - [Clinical observation of Flos magnoliae volatile oil nano-liposome nasal drops in
      treating pediatric allergic rhinitis].
AB  - OBJECTIVE: To observe the clinical efficacy of Flos Magnoliae volatile oil nano
      liposome nasal drops (FMO) in treating pediatric allergic rhinitis (PAR).
      METHODS: Adopting parallel controlled method, the 191 patients with PAR were
      randomized into two groups. The observation group was treated with FMO, and the
      control group with Cetirizine. The clinical efficacy, main symptoms, signs,
      syndromes scores of Chinese medicine, and peripheral eosinophil (EOS) count were
      observed after 3-week treatment. RESULTS: In the observation group, the total
      effective rate was 94.84%, which was higher than that in the control group
      (78.72%); the effective rate on alleviating main symptoms (sneezing, nasal
      obstruction), signs (nasal mucosa edema, pallor) and the EOS count were
      significantly lowered, all were better than those in the control group (P <0.05).
      CONCLUSION: FMO has some positive effects on PAR, it might be realized by
      lowering the peripheral EOS.

PMID- 19848212
TI  - [Application of patient-reported outcomes in clinical research on therapeutic
      efficacy].
AB  - Along with the transition of the socio-bio-psycho-medical mode, important change
      emerges in the program and criterion of clinical assessment, and the patient
      reported outcomes (PROs) has been stressed increasingly. The concept of PROs and
      its current state of research are introduced in this paper. The authors
      considered that the PROs researching mode, which takes the symptomatic effect
      evaluation as the main criterion, could be used as reference for the clinical
      efficacy assessment of Chinese medicine to create a scale evaluating system with
      Chinese medicine characteristics, for making its more objective and quantitative.
      It should contribute to the modernization and internationalization of Chinese
      medicine extensively.

PMID- 19848211
TI  - [Clinical observation of effect of jiawei yupingfeng mixture for prevention and
      treatment of 100 children with repeated respiratory tract infection].
AB  - OBJECTIVE: To investigate the effect of Jiawei Yupingfeng Mixture (YPF) on
      repeated respiratory tract infection (RRTI) and its impacts on T-cell subsets,
      immunoglobulin and erythrocyte immune. METHODS: Two hundred children with RRTI
      were assigned equally to two groups, the test group treated with YPF and the
      control group treated by transfer factor. The clinical efficacy, and the changes
      of T-cell subsets, immunoglobulin and erythrocyte immune before and after
      treatment were observed in 31 patients randomly selected from each group.
      RESULTS: After treatment, the frequency of attacking was reduced and the course
      of attacking was shortened significantly in the test group as compared with
      before treatment and also with the control group (P < 0.01); IgG and IgA levels
      were improved in both groups, but the improvement was more significant in the
      test group (P<0.01, P<0.05); T-cell subsets indices, including CD3(+), CD4(+),
      CD8(+) and CD4(+)/CD8(+) ratio, all improved in the test group significantly (P
      <0.01), while in the control group, significant improvement only showed in rising
      of CD3(+) and CD4(+) (P <0.05, P <0.01), comparison between groups showed
      significant difference in terms of CD3(+), CD4(+) and CD8(+); in the control
      group, levels of C3b, RFER and RFIR were changed significantly (P<0.05, P<0.01),
      but the improvement of ICR was insignificant, while in the test group, the above
      indices were significant improved as compared with after treatment of the control
      group (P <0.01). CONCLUSION: YPF plays a preventive and therapeutic role in
      children with RRTI by way of regulating the cellular and humoral immune.

PMID- 19848213
TI  - [Sub-health and the "treatment of pro-disease" in Chinese medicine].
AB  - The relationship between sub-health and " pro-disease" in Chinese medicine was
      clarified through analyzing the background of sub-health coming forth and its
      connotation, as well as the multiple meaning of "pro-disease" in Chinese
      medicine. The authors offered, thereupon, their clews and methods for treatment
      of "pro-disease" and intervention on sub-health.

PMID- 19848214
TI  - [Exploration into the cultural problems of Chinese medicine in English
      translation concerning foreign affairs ].

PMID- 19848215
TI  - [Progress of the application of Chinese medicine in the hemodialysis treatment].

PMID- 19848216
TI  - Fleck, anatomical drawings and early modern history.
AB  - In 2003, the historian of medicine Michael Stolberg, contested the argument-
      developed by Thomas Laqueur and Londa Schiebinger--that in the XVIII century,
      anatomists shifted from a one-sex to a two-sexes model. Laqueur and Schiebinger
      linked the new focus on anatomical differences between the sexes to the rise of
      egalitarian aspirations during the Enlightenment, and a consecutive need to
      ground male domination in invariable "laws of nature". Stolberg claimed that the
      shift to the two sexes model occurred in the early modern period, and was mainly
      motivated by developments within medicine. This article examines the 2003 debate
      on the origin of "two sexes" model in the light of a 1939 controversy that
      opposed the historian of medicine Tadeusz Bilikiewicz, who advocated a focus on a
      "spirit" of an earlier epoch, and the pioneer of sociology of science Ludwik
      Fleck, who promoted the study of the "thought styles" of specific scientific
      communities.

PMID- 19848217
TI  - Exoteric knowledge and esoteric knowledge. Ludwik Fleck, pedigrees and the
      visualization of pathological heredity.
AB  - In Genesis and Development of a Scientific Fact, Ludwik Fleck uses the concept of
      an "ideogram" to designate the representation of a thought style through an
      image, which condenses its features in graphic properties. Pedigrees are such
      ideograms used by scientists and health professionals on the one hand, patients
      and lay persons on the other hand. Building on Fleck's analysis of the
      relationships between esoteric circles and exoteric circles, this paper traces
      the transformation and uses of pedigrees in 20th century medicine. It suggests
      that pedigrees in eugenics, clinical medicine, human genetics, and molecular
      genetics have presented distinct and relatively stable characteristics,
      reflecting the changing boundaries and roles of esoteric and exoteric knowledge.

PMID- 19848218
TI  - Southern genes. Genetics and its institutions in the Italian South, 1930s-1970s.
AB  - The paper examines the historical vicissitudes of Genetics and Medical Genetics
      in the "Mezzogiorno", focussing on the emergence of local traditions and their
      mingling with international trends. The development of these disciplines took
      place in a peculiar mix of politics and science that lead to a rapid growth in
      the '50s and the '60s, followed by an harsh crisis. Though important and enduring
      results were attained, Italian genetics community failed to maintain the status
      reached in the two preceding decades, and quickly moved to the periphery of
      international networks.

PMID- 19848219
TI  - Researches on thalassemia and malaria in Italy and the origins of the "Haldane
      hypothesis".
AB  - This paper aims to shed light on Italian contribution to the origins of malaria
      hypothesis, also known as Haldane hypothesis. The first studies on the
      association between hemoglobinopathies and malaria, in fact, were done in Italy
      since the end of the 1920s. These studies tried to explain the correlation
      between malaria and thalassemia observed by clinicians in various Italian
      regions. Later, since the beginning of the 1940s, this singular correlation was
      documented by thorough and wide-ranging epidemiological researches that revealed
      a strong geographic correspondence between the frequency of the thalassemic
      features and endemic malaria in Italy. These researches raised clearly the
      question of maintaining the frequency of a gene that, at the time, doomed
      homozygotes to death within the first two years of life. In 1948, Silvestroni,
      Bianco and Montalenti started investigating the causes of the persistence of the
      thalassemic foci in Italy. In 1949 J.B.S. Haldane finally hypothised for the
      first time an evolutionary advantage of thalassemic condition due to the
      concomitant presence of malarial infection. Since 1948, Montalenti and Haldane
      had various occasions to discuss on this topic. I try to demonstrate the role of
      Silvestroni, Bianco and Montalenti's research and data on the formation of
      Haldane hyphothesis.

PMID- 19848220
TI  - The ubiquitous Mandarin. Notes on the social organization of elite medicine in
      the twentieth century.
AB  - The aim of this essay is to reflect on the prominence given to individuals in the
      history of medicine. Although modern medicine, just as modern science before, has
      grown in complexity to the point of implying a great number of actors engaged in
      highly institutionalized processes, the historiography of the field is still
      dominated by biographical research. The persistence of high level of
      individualization observed in elite medicine originates, first and foremost, in
      the "multipositionality" of prominent physicians. By holding positions in
      universities, hospitals, research institutes, and providing expertise to the
      public and the private sectors as well as non-profit organizations, medical
      Mandarins bridge the gap between the different social worlds of modern medicine.
      Building on a case study, namely the career of Robert Debre, I shed light on the
      specific qualities that are often attributed to such multipositional actors, and
      on the accumulation of "symbolic capital" that help legitimize their professional
      dominance.

PMID- 19848221
TI  - Social medicine in the interwar years. The case of Jacques Parisot (1882-1967).
AB  - Hygiene, asserted the "Pasteurians", is "the very base of politics". Professor of
      preventive medicine at Nancy medical school, the phtisiologist Jacques Parisot
      well epitomized the style of a discipline that had soon shown interest for the
      avenues of action. Just as many other practical minds in Europe and elsewhere, he
      lamented the discrepancies between medical innovation and organizational change.
      However, as a French Professor medicine he had more latitude than his foreign
      colleagues to try bringing together the laboratory, medical education and the
      clinics. Chair of the Health Committee of the League of Nations from 1937 to the
      war, Parisot is an interesting case of these "Statesmen in disguise": to him
      social medicine, a science for action, was nothing but a vehicle to improve the
      Welfare of the community.

PMID- 19848222
TI  - Daniel Bovet and his role in the development of psychobiology.
AB  - One hundred years since his birth, fifty years after his Nobel achievement,
      Daniel Bovet still emerges as one of the key figures of both pharmacology and
      psychobiology, the biological and evolutionary roots of behaviour. The life and
      scientific activities of Daniel Bovet (1907-1992) are closely linked to the
      'golden years' of pharmacology, the exceptional development of this science from
      the end of the 1930s to the 1960s. Later on, from the 1960s to the end of his
      scientific career, Bovet entered a new field, psychobiology, through the study of
      the effects of drugs active on the nervous system and their effects on behaviour.
      This approach led him to explore different aspects of the biology of behaviour,
      namely the role of individual differences, the genetic determinants of behaviour
      and their implications on learning and memory. It is therefore evident that the
      range of his scientific activity has been very broad, a fact difficultly
      conceivable in years of extreme specialization.

PMID- 19848223
TI  - Against UNESCO: Gedda, Gini and American scientific racism.
AB  - The aim of this article is to shed light on the ideological, institutional and
      intellectual connections between Italian eugenics and American scientific racism,
      from 1953 to 1967. The paper pays special attention to the scientific links
      between fascist demographer Corrado Gini (the first president of the Italian
      Central Statistical Institute - Istat), and geneticist Luigi Gedda (the president
      of the Gregor Mendel Institute in Rome and head of the Catholic political
      association Azione Cattolica) on the one hand, and on the other, the members of
      the IAAEE (International Association for the Advancement of Ethnology and
      Eugenics) and their journal, "The Mankind Quarterly". Corrado Gini and Luigi
      Gedda were both members of the honorary advisory board of "The Mankind
      Quarterly", and Gini was also assistant editor in 1962. Despite the theoretical
      differences between the "neo-Lamarckians" Gini and Gedda, and the "Mendelians"
      Robert Gayre and Reginald Ruggles Gates--editor and associate editor of "The
      Mankind Quarterly"--the relationship grew stronger because of a sort of strategic
      alliance in the ideological fight against UNESCO's Statements on Race. The main
      source of the paper is Corrado Gini's personal archive, deposited in Rome at the
      National State Archive (ACS).

PMID- 19848224
TI  - The doers of good. Scandinavian historians revise the social history of
      eugenics(1997-2001).
AB  - Late disclosure of the large scale of sterilization practices in the Nordic
      countries created an outburst of scandal: did these policies rely on coercion? To
      what extent? Who in the end was responsible? Sterilization practices targeted
      underprivileged people first. The mentally retarded and women were their first
      victims. Operations were very frequently determined by other people's
      manipulative or coercive influences. Should the blame be put on the Social
      Democrats in power throughout the period (except in Finland and Estonia)? Apart
      from Denmark, perhaps, local physicians and local services, more than
      governments, seemed to have strongly supported sterilization practices.
      Teetotalers and feminists shared responsibilities. How can one explain that
      eugenics finally declined? Based on a sound application of the Hardy-Weinberg
      law, the science of the eugenicists was correct. Was it politics? But uncovering
      of the Nazi crimes had only a very small impact on eugenics. Some authors
      underline the fact that the Nordic scientific institutions were particularly
      suited to liberal values. Others point to the devastating effect on eugenics once
      hereditarist psychiatry fell from favor in the middle of the sixties.

PMID- 19848225
TI  - Toward an evolutionary historiography and epistemology of medicine. The legacy of
      Mirko Grmek.
AB  - Mirko Grmek has proved that a naturalistic approach to the history of medicine is
      possible. In his works he showed that the historical and epistemological research
      can use different kind of conceptual tools and knowledge, borrowed from history,
      anthropology and medicine, to understand more deeply the historic development of
      medical thinking. Moving from Grmek original concept of "pathocenosis" is
      possible to link his ideas to the evolutionary perspective, present in the
      contemporary medical thought as "evolutionary medicine" or "Darwinian medicine".
      The last one sees the disease as an inconsistency between phenotypes and
      environmental conditions, and a by-product of the necessity to stock variations
      to respond to the mutability of external conditions. Today, the evolutionary
      approach to medicine gives us a new way for taking care of the sick. At the same
      time it supplies a new way to solve the eternal theoretical problem of
      determining a shared and consistent definition of the disease's concept and
      medicine status.

PMID- 19848226
TI  - [Historical heritage and medical progress: the destiny of the scientific
      collections in the 'modern' Hospital of Santa Maria Nuova in Florence].
AB  - The scientific collections of Florentine Santa Maria Nuova Hospital stimulated
      new interest in the second half of eigthteenth century. Indeed, the modernization
      process of the Hospital lead to a steadily increasing alienation of its rich
      historical heritage, including the scientific collections. Archive documents
      witness the sale or the museum valorization of a number of collections including
      mathematical instruments and the anatomical, surgical and wax-obstetrical ones.

PMID- 19848227
TI  - Architecture, religion, and tuberculosis in Sainte-Agathe-des-Monts, Quebec.
AB  - This paper explores the architecture of the Mount Sinai Sanatorium in Sainte
      Agathe-des-Monts (Qc) to disentangle the role of religion in the treatment of
      tuberculosis. In particular, we analyze the design of Mount Sinai, the jewel in
      the crown of Jewish philanthropy in Montreal, in relation to that of the nearby
      Laurentian Sanatorium. While Mount Sinai offered free treatment to the poor in a
      stunning, Art Deco building of 1930, the Protestant hospital had by then served
      paying patients for more than two decades in a purposefully home-like, Tudor
      revival setting. Using architectural historian Bernard Herman's concept of
      embedded landscapes, we show how the two hospitals differed in terms of their
      relationship to site, access, and, most importantly, to city, knowledge, and
      community. Architects Scopes & Feustmann, who designed the Laurentian hospital,
      operated an office at Saranac Lake, New York, America's premier destination for
      consumptives. The qualifications of Mount Sinai architects Spence & Goodman,
      however, derived from their experience with Jewish institutions in Montreal.
      Following Herman's approach to architecture through movement and context, how did
      notions of medical therapy and Judaism intersect in the plans of Mount Sinai?

PMID- 19848228
TI  - Images of the Toronto Provincial Asylum, 1846-1890.
AB  - Built in 1850, the Toronto Provincial Asylum was once the largest mental
      hospitals in Canada. The main building was demolished in 1975, and the property
      is now home to the Queen Street branch of the Centre for Addiction and Mental
      Health. Although there are remnants of the nineteenth-century institution,
      including most of the perimeter wall, the only lasting visual reminder of the
      property as a whole is a small group of images. By the last quarter of the
      nineteenth century, perhaps in order to ease public concern over the increasingly
      custodial function of the institution, Victorian media sources repeatedly
      presented an unchanging or immutable depiction of the Toronto Asylum. Drawing
      upon the architectural concept drawings of the 1840s, which contained an ideal
      vision for the building, pictures from the 1870s, 80s and 90s depict the asylum
      as the new, clean, and proud-looking structure it was when it opened. Arguably,
      these images are what the Victorian public wanted to see: they preserved the
      early-century optimism that such institutions would yield high cure rates and
      they supported the view that the care of the mentally ill belonged in the hands
      of the medical profession.

PMID- 19848229
TI  - Tower of power: the Drummond Medical Building and the interwar centralization of
      medical practice.
AB  - This paper focuses on Montreal's Drummond Medical Building (1929), designed by
      the well-known architectural firm of Nobbs & Hyde, as a case study of the new
      typology that emerged in urban Canada in the 1920s: a modern, purpose-built high
      rise for healthcare professionals, with elevators, telephones, indoor parking,
      and retail shops, located in an upscale commercial district. What role did
      medical high-rises play in the practice of modern medicine? We speculate that
      these clinics marked the end of the house-office era across Canada, centralizing
      the practice of healthcare professionals. This CIHR-funded project illustrates
      complex social and physical networks among architects and doctors, drawing
      attention to the importance of studying architecture as a technology in the
      history of modern medicine.

PMID- 19848230
TI  - [Shopping addiction--the new face of Mammon].

PMID- 19848231
TI  - [Female medical students in the servants' entrance, or medical history
      curiosities from the Hungarian history of emancipation].

PMID- 19848233
TI  - Analysis of gene expression profiles along the tonotopic map of mouse cochlea by
      cDNA microarrays.
AB  - CONCLUSION: This study demonstrated differential gene expression profiles along
      the axis of the mouse cochlea. It also suggests the mechanism that establishes
      the tonotopic organization. OBJECTIVES: The molecular basis of the tonotopic
      mapping of the mammalian cochlea remains unclear. We therefore examined the genes
      that were abundantly expressed in either the apex or the base of mouse cochlea.
      MATERIALS AND METHODS: Apical and basal portions of cochlea, which contained the
      organ of Corti and spiral ganglion neurons, were independently dissected from 10
      adult C57BL/6 mice, and their total RNAs were respectively isolated. The gene
      expression profiles of each of these two pools were examined and compared to each
      other by the complementary DNA microarray technique. RESULTS: Of 20,289 probes
      tested, 64 genes were found to be expressed in the apical portion more than
      fivefold more abundantly than in the basal portion, and 77 genes were vice versa.
      Of interest, the genes of several functional proteins such as beta2- and gamma2
      subunits of GABA(A) receptors dominated the basal part, indicating that these
      molecules may be involved in high-frequency tuning of the hair cells and/or
      ganglion neurons.

PMID- 19848232
TI  - Reelin-disabled-1 signaling in the mature rat cochlear nucleus.
AB  - CONCLUSION: Immunohistochemical detection of Reelin in granular cells and
      disabled-1 in cochlear nucleus suggests a possible Reelin signaling pathway in
      mature rat cochlear nucleus. MATERIALS AND METHODS: Six-week-old Wister rats were
      used throughout this study. The expression of reelin and disabled-1 were studied
      by using in situ hybridization technique and immunohistochemistry. RESULTS:
      Reelin mRNA expression was observed in granular cell layer of dorsal cochlear
      nucleus. Immunohistochemistry using anti-reelin monoclonal antibodies confirmed
      reelin expression in granule cells at protein level. We also examined disabled-1
      expression in cochlear nucleus and observed positive immunoreactivity in both
      ventricular and dorsal cochlear nucleus. In the dorsal cochlear nucleus, fusiform
      and cartwheel cells were labeled. In the ventricular cochlear nucleus, relatively
      large cells were labeled with anti-disabled-1 polyclonal antibody but the
      subtypes of disabled-1 positive cells could not be identified.

PMID- 19848234
TI  - Heme oxygenase-1 expression in the guinea pig cochlea induced by intense noise
      stimulation.
AB  - CONCLUSION: These results suggest that noise induces free radical formation in
      the cochlea and that, in the guinea pig, heme oxygenase-1 (HO-1) may play an
      important role in the recovery from noise trauma in the organ of Corti.
      OBJECTIVE: Free radicals are involved in noise-induced hearing loss. It has been
      demonstrated that the induction of HO-1 may protect cells exposed to oxidative
      challenge. The present study was designed to investigate the effect of intense
      noise exposure on HO-1 induction. MATERIALS AND METHODS: A total of 25 adult
      guinea pigs (body weight 200-300 g) with a normal Preyers's reflex were used as
      subjects. Based on preliminary tests, the appropriate intensities and durations
      of noise were determined that were adequate to induce apparent threshold shifts
      and lead to various recovery patterns to initial thresholds. The sound was routed
      through a power amplifier to a speaker, which was positioned directly over the
      animals in a sound chamber. Auditory brainstem response (ABR) testing, Western
      blot analysis for HO-1, and immunohistochemical testing were done. RESULTS:
      Exposure of the guinea pigs to 115 dB SPL octave band noise for 5 h induced HO-1
      expression in the organ of Corti. In the organ of Corti, HO-1 expression
      increased mainly in the outer hair cells. Some expression of HO-1 was observed
      before and after noise exposure in the supporting cells. HO-1 expression in the
      organ of Corti was definitely increased in guinea pigs with an intense noise
      exposure which causes a temporary threshold shift.

PMID- 19848235
TI  - Prednisolone prevents transient ischemia-induced cochlear damage in gerbils.
AB  - CONCLUSIONS: Prednisolone protects against inner ear damage, even when
      administered after ischemic injury in Mongolian gerbils. OBJECTIVE: The effect of
      prednisolone on ischemia-induced cochlear damage was investigated in Mongolian
      gerbils. MATERIALS AND METHODS: The bilateral vertebral arteries were occluded
      for 15 min to transiently induce cochlear ischemia, followed by an
      intraperitoneal injection of prednisolone (1 mg/kg) or physiological saline
      (control). Sequential changes in hearing were evaluated by recording the auditory
      brainstem response (ABR) before and at 1, 4, and 7 days after treatment. In our
      histologic analysis, the numbers of dead and intact inner hair cells (IHCs) were
      counted in specimens stained with rhodamine-phalloidin. RESULTS: In control
      animals, transient ischemia increased the ABR threshold (24.2 +/- 8.6 dB) within
      7 days of treatment, whereas prednisolone-treated animals exhibited a threshold
      of 14.2 +/- 9.2 dB. Furthermore, the percent IHC loss at the basal turn of the
      cochlea was 26.5 +/- 11.4% in control animals compared with 5.3 +/- 3.0% in the
      prednisolone-treated group.

PMID- 19848236
TI  - N1m amplitude growth function for bone-conducted ultrasound.
AB  - CONCLUSION: N1m growth indicates the differences in central auditory processing
      between bone-conducted ultrasound and air-conducted audible sound. OBJECTIVES:
      Bone conduction enables ultrasound to be heard by the human ear. Despite many
      studies, the perceptual mechanism of bone-conducted ultrasound has not yet been
      clarified completely. Therefore, this study investigated the ultrasonic
      perception of humans, especially as regards the effects of stimulus intensity or
      loudness. SUBJECTS AND METHODS: The effect of the stimulus level on N1m amplitude
      was measured over the psycho-acoustical dynamic range. RESULTS: The dynamic range
      for 30 kHz bone-conducted ultrasound (18.2 +/- 3.3 dB) was found to be
      significantly narrower than that for 1 kHz air-conducted sound (85.9 +/- 11.9
      dB). As the stimulus level increased, the N1m amplitude in response to bone
      conducted ultrasound grew faster than that to air-conducted sound. Although the
      growth of the N1m amplitude for air-conducted sound saturated below the
      uncomfortable loudness level (UCL), that for bone-conducted ultrasound continued
      to grow above the UCL.

PMID- 19848237
TI  - Comparison between bone-conducted ultrasound and audible sound in speech
      recognition.
AB  - CONCLUSION: This study showed that it is possible to transmit language
      information using bone-conducted ultrasound (BCU) in normal-hearing subjects. Our
      results suggest the possibility of a difference in speech recognition between BCU
      and air-conducted audible sound (ACAS). OBJECTIVE: Ultrasound was audible when
      delivered by bone conduction. Some profoundly deaf subjects as well as normal
      hearing subjects can discriminate BCU whose amplitude is modulated by different
      speech sounds. These findings suggest the usefulness of developing a bone
      conducted ultrasonic hearing aid (BCUHA). However, the characteristics of BCU are
      still poorly understood. The aim of the present study was to compare BCU and ACAS
      in terms of their associated speech perception tendency and to investigate the
      different perceptual characteristics of BCU and ACAS. SUBJECTS AND METHODS:
      Speech discrimination tests using both BCU and ACAS were performed with normal
      hearing subjects. BCU and ACAS were compared for intelligibility and hearing
      confusion. RESULTS: With BCU, the maximum percentage correct totaled about 75%.
      Our comparison of the hearing confusion with ACAS and BCU according to the
      individual syllabic nuclear group showed a clear difference in the incorrect
      rates. In addition, the stimulus nuclear groups were often perceived in other
      nuclear groups in BCU.

PMID- 19848238
TI  - Estimation of factors influencing the results of tinnitus retraining therapy.
AB  - CONCLUSION: The factors of tinnitus loudness and Tinnitus Handicap Inventory
      (THI) score in tinnitus patients have the potential to relate to therapeutic
      results of tinnitus retraining therapy (TRT). OBJECTIVES: To confirm what factors
      in tinnitus influence the results of TRT. PATIENTS AND METHODS: Twelve factors
      were investigated in 53 patients with tinnitus, examining the relationship
      between these factors and the results of TRT. A THI score was determined before
      and 6 months after TRT introduction (pre- and post-TRT). Moreover, the change of
      THI score from pre- to post-TRT (delta THI) was referred to as the therapeutic
      effect of TRT. Based on the 12 factors, subjects were respectively divided into
      two groups, comparing delta THI between groups. RESULTS: Two groups of greater
      tinnitus loudness and higher THI score showed significant increases in delta THI,
      indicating that two factors of tinnitus loudness and THI score were related to
      the therapeutic effect of TRT.

PMID- 19848239
TI  - Subjective visual vertical test in patients with chronic dizziness without
      abnormal findings in routine vestibular function tests.
AB  - CONCLUSION: The subjective visual vertical (SVV) test can detect abnormality of
      the otolithic organs and the graviceptive pathways present in a considerable
      number of patients having dizziness but presenting no abnormal findings in
      conventional vestibular function tests. OBJECTIVE: To evaluate whether the SVV
      test can detect dysfunction of the otolithic organs and perception of gravity in
      patients with dizziness having no abnormal finding on routine tests for the
      vestibular system. PATIENTS AND METHODS: Forty-four patients who complained of
      chronic dizziness but had no abnormal finding on routine tests for vestibular
      system and on brain MRI studies were selected between 2004 and 2006. SVV tests
      were performed on these patients. Patients with chronic dizziness caused by
      apparent psychogenic disorders, such as depression, were excluded. RESULTS: Among
      the 44 patients, 3 showed abnormal tilts of SVV. The latter three patients had
      deep white matter hyperintensities on their MRI, probably due to aging.

PMID- 19848240
TI  - Two cases of spinal cord extramedullary tumor with positional vertiginous
      sensation.
AB  - CONCLUSIONS: We conclude that neck imaging should be carried out for patients
      with persistent paroxysmal positional vertigo following diagnostic and/or
      therapeutic maneuvers. OBJECTIVE: It is sometimes complicated to diagnose
      patients with vertigo that is transiently induced by head and neck positioning.
      Neck-vestibular diseases also induce vertiginous sensation with head and neck
      movement and need to be ruled out for the diagnosis of benign paroxysmal
      positional vertigo (BPPV). PATIENTS AND METHODS: Two elderly female patients
      visited our hospital with complaints of transient vertigo induced by Dix-Hallpike
      positioning, suggesting posterior canal BPPV. We carried out gadolinium-enhanced
      neck MRI in both these cases. RESULTS: The positional nystagmus was not clearly
      observed or vertiginous sensation did not show any decay during repeated
      vestibular examination in either case. These cases were finally diagnosed as
      spinal cord intradural extramedullary tumor (C3-C4) by means of neck MRI.

PMID- 19848241
TI  - A case with posterior fossa epidermoid cyst showing audiovestibular symptoms
      caused by insufficiency of anterior inferior cerebellar artery--usefulness of
      free DICOM image viewing and processing software.
AB  - A 58-year-old Japanese man suddenly suffered from vertigo. On physical
      examination, left-beating horizontal torsional spontaneous nystagmus was
      observed; the direction did not change with gaze. Other neurotological
      examinations revealed findings within normal limits except the left side
      sensorineural hearing loss of approximately 32 dB on average. Diffusion-weighted
      MRI revealed no infarction in the brain, but demonstrated an epidermoid cyst in
      the left cerebello-pontine cistern region. Using free digital imaging and
      communications in medicine (DICOM) image viewing and processing software, it was
      found that the epidermoid cyst clearly compressed the left anterior inferior
      cerebellar artery (AICA). Therefore, we speculated that insufficiency of the left
      AICA caused his audiovestibular symptoms. This new technique used in the present
      study was considered useful when the site responsible for vertigo is suspected in
      the cerebello-pontine angle, where anatomic relationships between the nerves and
      the vessels are complicated.

PMID- 19848243
TI  - Oxygen consumption by bacteria: a possible cause of negative middle ear pressure
      in ears with otitis media.
AB  - CONCLUSIONS: Oxygen consumption by bacteria could be a cause of the negative
      middle ear pressure in ears with otitis media (OM). OBJECTIVE: To determine
      whether oxygen consumption by bacteria could be a cause for production of
      negative pressure in ears with OM. MATERIALS AND METHODS: Hermetically sealed
      bottles containing high dose (group A) and low dose (group B) of Streptococcus
      pneumoniae with air space and maintained at 37 degrees C in a water bath were
      connected to a micropressure sensor. The chronological pressure changes were
      monitored in vitro for 3-13 h and were compared with those in the control bottles
      containing culture medium only. RESULTS: The pressure of the group A samples
      showed significantly lower values than that of controls 3 h later (p<0.0001). In
      group B, the pressure was also significantly lower than that in the control group
      (p<0.0001). The partial pressures of oxygen measured at the beginning and end of
      the experiment in the six samples in group B showed significant decrease, while
      that in the control group showed only a slight decrease (p<0.0019).

PMID- 19848242
TI  - Poly(I:C) synergizes with Th2 cytokines to induce TARC/CCL17 in middle ear
      fibroblasts established from mucosa of otitis media with effusion.
AB  - CONCLUSION: These results suggest that middle ear fibroblasts contribute to the
      recruitment of Th2 cells into the middle ear by producing thymus and activation
      regulated chemokine (TARC). OBJECTIVES: Intractable otitis media is more common
      in atopic subjects and asthmatics than in the otherwise normal population.
      Although type 2 T helper (Th2) cytokines play crucial roles in the middle ear of
      these populations, the mechanism underlying the predominance of Th2 cytokines has
      yet to be clarified. TARC has been known to facilitate recruitment of Th2
      polarized cells, resulting in high levels of Th2 cytokines in the middle ear. We
      investigated whether middle ear-derived fibroblasts produce TARC when stimulated
      with poly(I:C) and Th2 cytokines (IL-4, IL-13). MATERIALS AND METHODS: Fibroblast
      lines were established from middle ear mucosa. TARC mRNA expression was evaluated
      by real-time RT-PCR. The amount of TARC in the culture supernatants was measured
      by ELISA. RESULTS: Poly(I:C) induced only TARC gene expression in middle ear
      derived fibroblasts. Combined stimulation with poly(I:C) and Th2 cytokine (IL-4,
      IL-13) synergistically induced TARC production by the cultured middle ear-derived
      fibroblasts. This response was dose and time dependent.

PMID- 19848244
TI  - Localization of aquaporins, water channel proteins, in the mouse eustachian tube.
AB  - CONCLUSION: Immunolocalization of the subtypes of water channel proteins,
      aquaporins (AQPs), was detected in the mouse eustachian tube (ET). AQPs are
      located continuously from the serous glands and the capillary vessels to the
      luminal side in the ET epithelium and may play an important role in the
      transportation of water to the surface of the ET lumen through the epithelium.
      OBJECTIVES: Although the water supply to the surface of the ET lumen is
      considered to be essential for closing of the ET, the pathway of the water in the
      ET is not fully understood. Since AQPs, a group of water transport proteins, have
      been reported to regulate water homeostasis, we examined the location of AQPs in
      the mouse ET. MATERIALS AND METHODS: Nine subtypes of AQPs were examined in
      paraffin embedded ETs of adult mice using the avidin-biotin peroxidase complex
      method of immunohistochemistry. RESULTS: Four subtypes of AQPs were detected in
      the mouse ET. AQP-1 was detected in fibroblasts, endothelial cells of capillary
      vessels and cartilage cells. AQP-3 was distinctly detected in the basal membrane
      of epithelial cells. AQP-4 was detected in the basal membrane of epithelial
      cells. AQP-5 was expressed in the luminal side of the ET epithelial cells and
      also in the apical surface of the cells of the serous glands.

PMID- 19848246
TI  - Functional optical hemodynamic imaging of the olfactory cortex in normosmia
      subjects and dysosmia subjects.
AB  - CONCLUSION: These activated areas may be related to the orbitofrontal cortex,
      corresponding to olfactory cortices. This study shows that multichannel near
      infrared spectroscopy (NIRS) enables the evaluation of brain activity of
      normosmia subjects and dysosmia subjects by olfactory stimulation. OBJECTIVE:
      Objective olfactory testing is not common. NIRS has beenused before to study
      functional activations in various areas of the brain, but we wanted to
      investigate the difference in brain olfactory activity in normosmia subjects and
      dysosmia subjects using multi-channel NIRS (MNIRS). SUBJECTS AND METHODS: This
      study was conducted on eight normosmia subjects and five dysosmia subjects. We
      employed a 22-channel near-infrared spectroscopy device with eight light incident
      fibers and seven light detector fibers, each with an inter-optode distance of 2.5
      cm on the frontal head. Isovaleric acid was used as the odor stimulant. We
      measured the change in oxyhemoglobin concentrations [oxyHb], deoxyhemoglobin
      concentrations [deoxyHb], and total hemoglobin concentrations [totalHb] from pre
      baseline values. Furthermore, we divided the frontal cortex into four areas
      (right upper, left upper, right lower, left lower) and measured the activity in
      each area. Then, the changes in [oxyHb], [deoxyHb], and [totalHb] of normosmia
      subjects and dysosmia subjects were compared in each area. RESULTS: In all
      normosmia subjects, isovaleric acid caused remarkable changes, especially in the
      lower areas of the frontal cortex. However, in all dysosmia subjects, isovaleric
      acid caused no changes.

PMID- 19848245
TI  - Taste disturbance after stapes surgery--clinical and experimental study.
AB  - CONCLUSION: Most of the clinical cases experienced taste disturbance after stapes
      surgery, and in a few cases this disturbance persisted for a long time. The
      animal experiment suggested the role of geniculate ganglion (GG) cells in nerve
      generation. OBJECTIVES: To clinically examine taste disorder and its recovery
      after stapes surgery and experimentally demonstrate a role of GG. PATIENTS AND
      METHODS: Taste function after preservation of chorda tympani nerve (CTN) in
      stapes surgery was prospectively investigated with a questionnaire and
      electrogustometry (EGM). Further, expression of neurotrophic factors in GG after
      injury of CTN was examined by in situ hybridization histochemistry (ISSH) and RT
      PCR. RESULTS: Among the cases, 15/18 (83.3%) were associated with taste
      disturbance and 6/18 (33.3%) were associated with tongue numbness 2 weeks after
      surgery; however, the symptoms ceased in 14/18 cases (77.8%). Two weeks after
      surgery, the EGM threshold was found to be elevated in 15/18 cases (83.3%), while
      in 10/18 cases (55.6%), it did not decrease until 1 year after surgery.
      Expression of ISSH and amplified bands of BDNF and GFR increased at 7 and 14 days
      after nerve injury in ipsilateral GGs and also increased at 7 days on the
      contralateral side.

PMID- 19848247
TI  - Functional MRI of regional brain responses to 'pleasant' and 'unpleasant' odors.
AB  - CONCLUSIONS: Our findings demonstrate that functional MRI (fMRI) combined with a
      questionnaire is a useful method for studying the neuroanatomy of olfaction.
      Further studies with various odorants and questionnaires would provide an even
      better understanding of the mechanism of olfactory perception. OBJECTIVES: To
      better understand the mechanism of odorant perception in the central nervous
      system. SUBJECTS AND METHODS: fMRI was used to identify the activated regions
      during stimulation by two odorants, beta-phenyl ethyl alcohol and gamma
      undecalactone. Participants were asked to describe the quality of the odor and to
      rate odor intensity and odor hedonic valence. Activation at each region was
      statistically analyzed according to the answers. RESULTS: The bilateral middle
      orbitofrontal cortex (OFC), left lateral OFC, right insula, and bilateral
      anterior/middle cingulate gyri were most frequently activated by odor
      stimulation. Left middle OFC was significantly more often activated in the
      participants who could not identify the odor correctly (p = 0.016). The left
      middle OFC and right lateral OFC were significantly more often activated in the
      participants who perceived the odor stimulation as unpleasant (p = 0.03), while
      the right anterior cingulate gyrus was more often activated in those who
      perceived the odor as pleasant (p = 0.03).

PMID- 19848248
TI  - Usefulness of curry odorant of odor stick identification test for Japanese in
      olfactory impairment screening.
AB  - CONCLUSION: The curry odorant of the odor stick identification test for Japanese
      (OSIT-J) is useful in screening for olfactory impairment in Japanese subjects.
      OBJECTIVE: The present study was designed to determine the most useful odorant of
      the OSIT-J in screening for olfactory impairment in Japanese subjects. SUBJECTS
      AND METHODS: We studied olfactory impairment screening with the OSIT-J in 83
      participants (49 male, 34 female; average age 50 years) in an executive check-up
      at NTT West Kanazawa Hospital. Olfactory discrimination acuity was evaluated with
      three odorants of the OSIT-J (rose, curry, and sweaty-smelling clothes), each
      known to be significantly correlated with the assessment of the Japanese standard
      olfaction test (T&T olfactometer). Those participants who did not score full
      marks in tests with the three odors were assessed with another nine odorants of
      the OSIT-J. RESULTS: The positive predictive value was 100% in the screening with
      the curry odorant. In 38 participants who did not identify all three odors
      correctly, the identification of the curry odor was significantly correlated with
      the scores for all 12 odors (p<0.005). Identification of the curry odor was not
      significantly correlated with identification of the menthol odor of OSIT-J.

PMID- 19848249
TI  - Glucocorticoid receptor immunoreactivity of eosinophils in nasal polyps.
AB  - CONCLUSION: The higher level of glucocorticoid receptor (GR) expression in cases
      of chronic sinusitis with bronchial asthma or allergic rhinitis suggests that
      glucocorticoids may exert a greater influence on eosinophils, thereby making them
      more effective in the treatment of polyps or chronic sinusitis. OBJECTIVES: The
      GR immunoreactivity of eosinophils in nasal polyps was investigated to elucidate
      the mechanism by which glucocorticoids interact with eosinophils. MATERIALS AND
      METHODS: Nasal polyp specimens were divided into 3 groups: 7 patients with
      chronic sinusitis alone (CS only group), 12 patients with chronic sinusitis
      complicated by perennial allergic rhinitis (CS/AR group), and 6 patients with
      chronic sinusitis complicated by bronchial asthma except for aspirin-induced
      asthma (CS/asthma group). Immunofluorescent staining with an anti-GR polyclonal
      antibody and anti-major basic protein (MBP) monoclonal antibody was used.
      RESULTS: The total number of MBP+ cells, GR+ cells, and MBP+/GR+ cells in the
      CS/asthma group was significantly higher than that in the other two groups. The
      total number of these cells in the CS/AR group was also higher than that in the
      CS only group The ratio of MBP+/GR+ cells to GR+ cells was highest in the
      CS/asthma group. The ratio of MBP+/GR+ cells to MBP+ cells in the CS only group
      was lower than those in the other two groups.

PMID- 19848250
TI  - Expression of antiviral molecular genes in nasal polyp-derived cultured
      epithelial cells.
AB  - CONCLUSION: The results of the present study indicate the existence of natural
      immunity mechanisms via which viruses are eliminated from nasal and paranasal
      sinus mucosa. OBJECTIVES: Acute sinusitis and acute aggravation of chronic
      sinusitis are often caused by bacteria, which are secondary to viral infection of
      the nose. Antiviral molecules are considered to be expressed and protect the host
      after viral infection. We investigated the expression of antiviral molecules
      after viral infection of the nose. MATERIALS AND METHODS: We assessed the
      expression of antiviral molecules, defensin and interferon mRNA, by the real-time
      polymerase chain reaction (PCR) technique after stimulating cultured nasal polyp
      cells with polyinosine-polycytidylic acid (poly(I:C)), which is an analog of
      double-stranded (ds) RNA. RESULTS: The expression of beta-defensin mRNA
      significantly increased after the stimulation. On the other hand, expression of
      both interferon-alpha mRNA and interferon-beta mRNA was recognized, but only the
      expression of interferon-beta mRNA increased after the stimulation.

PMID- 19848251
TI  - Double-stranded RNA poly(I:C) enhances matrix metalloproteinase mRNA expression
      in human nasal polyp epithelial cells.
AB  - CONCLUSION: The significant up-regulation of matrix metalloproteinase (MMP)-9
      mRNA, which is not modulated by tissue inhibitor of metalloproteinase (TIMP)-1,
      is an additional source of increased proteolytic activity in virus-infected upper
      airways that might contribute to the exacerbation of chronic rhinosinusitis with
      nasal polyps. OBJECTIVES: Chronic rhinosinusitis is often exacerbated by viral
      infection. We hypothesized that a disruption of the mechanisms that regulate the
      activity of MMPs during viral infection is one possible mechanism responsible for
      the exacerbation. In the present study we attempted to achieve a better
      understanding of MMP expression in nasal epithelial cells after viral infection.
      MATERIALS AND METHODS: Human nasal epithelial cells were isolated from nasal
      polyp specimens obtained during endoscopic endonasal surgery in chronic
      rhinosinusitis patients. We investigated the expression of MMP-2, MMP-9, and TIMP
      1 mRNA in primary human nasal polyp epithelial cells after dsRNA stimulation.
      RESULTS: Among the genes whose expression was evaluated, only expression of MMP-9
      mRNA increased significantly after dsRNA stimulation.

PMID- 19848252
TI  - A relationship between mast cells and alpha-smooth muscle actin-positive cells in
      the nasal polyps of chronic rhinosinusitis.
AB  - CONCLUSION: These results suggest that mast cells (MCs) play a role in promoting
      nasal polyp (NP) formation and progression with alpha-smooth muscle actin (alpha
      SMA)-positive cells. OBJECTIVES: We studied the quantification and the
      localization of MCs and myofibroblasts in NPs. PATIENTS AND METHODS: We examined
      NPs from 12 patients with chronic rhinosinusitis undergoing endoscopic sinus
      surgery. MCs and myofibroblasts that expressed alpha-SMA were detected
      immunohistochemically. The numbers of labeled cells were quantified in NPs. These
      cells were evaluated in the tip, central, and pedicle areas. The number of MCs
      was compared between low (zone 1), moderate (zone 2), and high (zone 3) zones of
      alpha-SMA-positive cells. RESULTS: The number of MCs was significantly higher in
      pedicle areas than in tip areas of NPs. The distribution of alpha-SMA-positive
      cells tended to be more remarkable in pedicle areas than in tip and central areas
      of NPs. The number of MCs was significantly higher in zone 3 than in zone 1 of
      alpha-SMA-positive cells.

PMID- 19848253
TI  - Neuromuscular junctions of the posterior cricoarytenoid muscle in multiple system
      atrophy: a case study.
AB  - CONCLUSION: The present study showed a variety of stages of neurogenic
      degeneration of the muscle fibers and the neuromuscular junctions (NMJs) of the
      posterior cricoarytenoid (PCA) muscle in multiple system atrophy (MSA). These
      findings coincide with abductor paralysis of vocal cords. Ultrastructural
      features of the NMJs of the PCA muscle in MSA were different from those of
      previous studies on experimental resection of recurrent nerve and amyotrophic
      lateral sclerosis (ALS). OBJECTIVES: MSA may influence various respiratory
      functions. Upper airway tracts including larynx are affected without exception
      during its clinical course. Morphological changes of NMJs of the intrinsic
      laryngeal muscle in MSA were examined ultrastructurally. PATIENT AND METHODS: The
      patient was a 68-year-old male complaining of recurrent aspiration pneumonia,
      dysphagia, respiratory disturbance, and abductor paralysis of vocal cords. The
      motor nerve terminals of the PCA muscle in a patient with MSA were investigated
      electron microscopically. RESULTS: The NMJs showed varying degrees of
      ultrastructural changes by motor nerve degeneration. They were seen in the pre-
      and post-synaptic regions. Muscle fibers losing nerve terminals showed severe
      damage in their cytoplasm.

PMID- 19848254
TI  - [Prevalence and potential predictors of morbidity among Hungarian female
      physicians].
AB  - BACKGROUND: We explored the general health status of physicians in Hungary using
      a nationwide sample. Based on international and Hungarian literature, we
      hypothesised that the prevalence of psychiatric and somatic morbidity is higher
      among female physicians in Hungary compared to the normative population. SUBJECTS
      AND METHODS: The objective of our cross-sectional research was to study the
      morbidity of Hungarian female physicians as well as to analyse background
      factors. Data for this national study were collected from 408 female physicians.
      818 white collar workers from a representative survey (Hungarostudy 2002) served
      as controls. RESULTS: The prevalence of chronic somatic morbidity and
      reproduction disorders among female physicians was significantly higher than that
      in the control group. The female physicians have more chronic diseases, and the
      somatic morbidity have been appeared earlier. Correlation analyses confirmed a
      significant relationship: the chronic morbidity associated with injurious to
      health, sleep disorders and higher levels of work-family conflict. We found that
      the prevalence of chronic somatic morbidity among female physicians was
      significantly higher than that in the respective control groups. CONCLUSION: The
      higher prevalence of somatic and mental morbidity of Hungarian female physicians
      has important consequences. This may influence health care systems and thus might
      lead increased morbidity and mortality of Hungarian population.

PMID- 19848255
TI  - [What worries Hungarian men? Characteristics of masculine gender role stress].
AB  - INTRODUCTION: The aim of this study was to establish the characteristics of
      stress associated with male gender role and its relationship to health and to
      risk behaviours among Hungarian men. SUBJECTS AND METHODS: The present analysis
      is based on data of the Hungarostudy 2006 survey. Forty-one percent of the
      participants were men. Eighty nine percent of the male respondents completed the
      Eisler-Skidmore Masculine Gender Role Stress Scale; data of 1764 persons were
      analyzed. RESULTS: Anxiety about sexual performance, breadwinner role, and
      appearance (i.e. tradition factor) causes a much greater burden of stress than
      anxiety about changing gender relationships (i.e. modernization factor). With the
      increase of age, stress caused by traditional role expectations significantly
      decreases; tensions caused by women's dominance and by situations which demand
      emotional response and empathy are the highest among middle aged men. Traditional
      gender role stress is more prevalent among pensioners than among economically
      active men; stress caused by the modernization of masculine gender role
      particularly afflicts unemployed men. Married men are to the least extent
      troubled by female dominance and difficulties in expressing emotions. Of the two
      dimensions analyzed here (tradition and modernization) only the values on the
      tradition factor were related to health status, psychological wellbeing, and
      frequency of smoking. CONCLUSIONS: Modernization of gender roles represents only
      a small--if any--stressor in the life of Hungarian men; on the other hand,
      unsuccessful adaptation to traditional role expectations highly increases the
      burden of stress and is closely related to smoking.

PMID- 19848256
TI  - [Addenda to the life of Albert Szent-Gyorgyi ].

PMID- 19848257
TI  - [Female doctors in the early history of European medicine].

PMID- 19848258
TI  - [Medical leaders and hired foreign doctors at Hizen-Saga district of Japan in the
      late Edo and the Meiji eras].

PMID- 19848259
TI  - [Doctors of Saga Clan, Chian Sagara and German medicine].

PMID- 19848260
TI  - [Medical persons at the end of the Tokugawa Shogunate that have appeared in the
      'Rakugo', traditional comic storytellings].

PMID- 19848261
TI  - [A far-sighted man, Tsunetami Sano].

PMID- 19848262
TI  - [The smallpox vaccination which Saga Feudal Clan had introduced over the whole
      country].

PMID- 19848263
TI  - The physiological roles of the boar ejaculate.
AB  - During ejaculation in the boar, sperm cohorts emitted in epididymal cauda fluid
      are sequentially exposed and resuspended in different mixtures of accessory sex
      gland secretion. This paper reviews the relevance of such unevenly composed
      fractions of seminal plasma (SP) in vivo on sperm transport and sperm function
      and how this knowledge could benefit boar semen processing for artificial
      insemination (AI). The firstly ejaculated spermatozoa (first 10 ml of the sperm
      rich fraction, SRF [P1]) remain mainly exposed to epididymal cauda fluid and its
      specific proteins i.e. various lipocalins, including the fertility-related
      prostaglandin D synthase; than to prostatic and initial vesicular gland
      secretions. P1-spermatozoa are hence exposed to less bicarbonate, zinc or
      fructose and mainly to PSP-I spermadhesin; than if they were in the rest of the
      SRF and the post-SRF (P2). Since the P1-SP is less destabilizing for sperm
      membrane and chromatin, P1-spermatozoa sustain most in vitro procedures,
      including cryopreservation, the best. Moreover, ejaculated firstly, the P1
      spermatozoa seem also those deposited by the boar as a vanguard cohort, thus
      becoming overrepresented in the oviductal sperm reservoir (SR). This vanguard SR
      entry occurs before the endometrial signalling of SP components (as PSP-I/PSP-II
      and cytokines) causes a massive influx of the innate defensive PMNs to cleanse
      the uterus from eventual pathogens, superfluous spermatozoa and the allogeneic
      SP. The SP also conditions the mucosal immunity of the female genital tract, to
      tolerate the SR-spermatozoa and the semi-allogeneic conceptus. These in vivo
      gathered data can be extrapolated into procedures for handling boar spermatozoa
      in vitro for AI and other biotechnologies, including simplified cryopreservation.

PMID- 19848264
TI  - Molecular kinetics of proteins at the surface of porcine sperm before and during
      fertilization.
AB  - Fertilization is a decisive moment in life and enables the combination of the DNA
      from two gametes to ultimately form a new organism. The sperm surface, especially
      the head area, has distinguishable subdomains that are involved in distinct
      fertilization processes. It is known that the sperm head surface undergoes
      constant remodelling during epididymal maturation and migration in the male and
      female genital tract. But intriguingly, the identity, origin and spatial ordering
      of proteins at the sperm surface that are involved in mammalian fertilization are
      essentially unknown. This review deals with sperm surface protein modifications
      that are under somatic cell control. As soon as the sperm is released from the
      seminiferous tubules it is subjected to these modifications. These surface
      reorganisations continue until the sperm reside in the fallopian tube where they
      meet the oocyte and may fertilize it. Most likely, a selective process allows
      only functionally mature and intact sperm to optimally interact and fertilize the
      oocyte. Recent data suggest that even the perivitelline fluid is involved in
      sperm surface remodelling as it contains factors which could facilitate the first
      penetrating sperm to fertilize the oocyte. In this contribution, the kinetics of
      proteins at the sperm surface will be overviewed. Better understanding of this
      would help to design strategies to improve male fertility or to devise novel
      contraceptives.

PMID- 19848265
TI  - Optimal characteristics of spermatozoa for semen technologies in pigs.
AB  - Despite the great potential of sperm technologies such as sperm cryopreservation
      and sperm sex sorting for the improvement of different aspects of swine
      production, artificial insemination with fresh or stored semen is currently the
      only sperm technology used at a commercial scale in the pig industry. The lower
      reproductive performance associated with the use of these sperm technologies is
      the reason for such limited use. Since optimal characteristics are required for
      successful application of frozen-thawed and sex-sorted boar spermatozoa, the
      present paper summarises the value of the current available methods for their
      functional assessment as well as the effects of these technologies on boar sperm
      functionality. In addition, strategies developed to reduce sperm damage and
      improve the yields of both sperm technologies in swine production are also
      reviewed with particular attention to the contributions of the authors.

PMID- 19848266
TI  - Recent advances in boar semen cryopreservation.
AB  - Since 35 years ago boar semen has been frozen and used for artificial
      insemination (AI). However, fertility of cryopreserved porcine sperm has
      consistently been low as boar sperm are more sensitive to cellular stress imposed
      by changing osmotic balance, oxidative stress, low-temperature exposure, cryo
      protectant intoxication etc. and are less able to compensate for these
      deficiencies at commercially applicable dosages. Additionally, differences in
      sperm freezability among individuals are well known. Here we review current
      advances on tests to screen sperm quality post-thaw, on ways of diminishing
      individual boar effects, on improvement of cryo-protection by novel extender
      components, on packaging and freezing protocols and freezing and thawing methods,
      and on the handling of sexed boar sperm. Major advances have been registered,
      which have improved cryo-survival and the capacity to process boar semen for
      commercial AI.

PMID- 19848267
TI  - Selection for boar fertility and semen quality--the way ahead.
AB  - Critical needs for the swine industry in terms of boar fertility evaluations are
      validation of semen quality estimates with in vivo reproductive data; estimation
      of the relative fertility of boars; and elimination of sub-fertile ejaculates.
      Single sire matings are the best way to validate semen quality estimates with
      reproductive performance. Sampling about 20% of the population provides an
      accurate estimation of the variability among boars and should be sufficient for
      this purpose. In vitro tests that measure univariate characteristics of
      ejaculates including motility and morphology appear to be just as accurate as
      those that measure multivariate traits such as in vitro fertilization in terms of
      predicting boar fertility. Reasons for this observation may be related to how
      properties of sperm cells are influenced by the sow reproductive tract. Several
      seminal plasma proteins show strong correlations with boar fertility and hold
      potential for being developed into tests that can rank the relative fertility of
      boars. Almost 90% of the variation in boar fertility was explained when the
      proportion of motile and acrosome-reacted spermatozoa was combined with relative
      amounts of 28 kDa, pl 6.0 and 55 kDa, pl 4.5 seminal plasma proteins.
      Consequently, combining different complementary tests improves estimations of
      boar fertility. Motility estimates routinely performed in most A.I. centres are a
      reasonable technique for identification and elimination of sub-fertile
      ejaculates. However, the accuracy with which they currently are conducted within
      the swine industry needs improvement.

PMID- 19848268
TI  - Changes in responsiveness to bicarbonate under capacitating conditions in liquid
      preserved boar spermatozoa in vitro.

PMID- 19848269
TI  - Intrauterine insemination of sows by using a two-chamber semen bag system.

PMID- 19848270
TI  - Binding of porcine spermatozoa to uterine epithelial cells modulates the female
      immune response and might indicate the formation of a pre-oviductal sperm
      reservoir.

PMID- 19848271
TI  - Sperm survival following colloid centrifugation varies according to the part of
      the sperm-rich fraction used.

PMID- 19848272
TI  - The role of gene discovery, QTL analyses and gene expression in reproductive
      traits in the pig.
AB  - The reproductive performance of the sow is one of the key factors affecting
      production profitability of the pig industry. Reproductive traits are in general,
      lowly heritable, and with reliable markers, they can be used to enhance current
      selection procedures for improvement of these traits. To find potential markers,
      large scale quantitative trait loci (QTL) and candidate gene studies have been
      conducted for reproductive traits. The present review discusses QTL and candidate
      gene discovery, large scale SNP association studies, gene expression profiling
      and discovery of miRNA regulation of pig reproductive tissues. Many QTL have been
      found for reproduction traits and a limited number of useful genes (e.g.: ESR1,
      PRLR, FSHB, EPOR and RBP4) have been found to have significant associations with
      reproductive traits. Expression studies with reproductive tissues have revealed
      differential expression within a few gene networks which need further mapping and
      association analyses to select prospective gene markers. The near completion of
      the pig genome sequence and the development of high density SNP chips will allow
      for large scale SNP association studies for pig reproductive traits in the
      future. Collection of appropriate phenotypes in large numbers and in broad
      populations representative of the swine industry are required if such genomic
      studies will ultimately be successful.

PMID- 19848273
TI  - Proteomic analysis of mammalian gametes and sperm-oocyte interactions.
AB  - Proteomic analysis occupies an increasingly important place in gamete and embryo
      biology as an independent tool of discovery and as a means of follow-up to
      transcriptional profiling. Proteomics have been and will be increasingly helpful
      in many areas of reproductive biology, including applied science and technology
      development. Areas likely to be impacted most rapidly by proteomic knowledge
      include fertility evaluation in male farm animals, male infertility diagnostics
      in humans, assessment and optimization of oocyte and embryo culture protocols,
      selection of fittest oocytes for assisted fertilization and selection of most
      competent embryos for embryo transfer. Oocyte proteomics will help us understand
      the process of oogenesis and oocyte maturation, and to discover non-invasive
      markers of oocyte quality. Sperm proteomics correlate with normal sperm structure
      and function and can be applied to discover novel biomarkers of farm animal
      fertility and diagnostic markers of human male infertility. Putative receptors
      participating in fertilization, as well as proteins acquired onto sperm surface
      from epididymal fluid and seminal plasma, have been discovered by proteomic
      analysis. An added level of information is provided by advanced proteomic
      approaches, capable of identifying posttranslational modifications such as
      phosphorylation, glycosylation and ubiquitination which play important functions
      in gametogenesis, fertilization and embryo development. By no means exhaustive,
      the present paper reviews some of the most interesting proteomic studies of
      mammalian gametes and embryos published in the last decade.

PMID- 19848274
TI  - Mapping quantitative trait loci for reproduction in pigs.

PMID- 19848275
TI  - Global protein profiling of porcine cumulus cells in response to native oocyte
      secreted factors in vitro.

PMID- 19848276
TI  - Nutritional and lactational effects on follicular development in the pig.
AB  - In sows, follicular development is inhibited during lactation, and weaning the
      piglets allows recruitment and selection of follicles that will undergo
      preovulatory maturation and ovulate. Lactation inhibits GnRH secretion, and in
      turn LH secretion, through neuroendocrine stimuli induced by suckling. Pituitary
      response to GnRH and the sensitivity of the hypothalamo-pituitary unit to
      oestradiol positive feedback are also reduced. The impact of lactation on the
      reproductive axis is further complicated by the physiological and metabolic
      adaptations that are developed for milk production and that depend on nutrient
      intake, nutrient needs and body reserves. A strongly catabolic state during
      lactation amplifies the inhibition of LH secretion, thereby inducing a delay of
      oestrus and ovulation after weaning. Nevertheless, post-weaning ovulation is less
      delayed nowadays than in the 1970's or 80's. Nutritional deficiency has also
      deleterious effects on embryo survival, which are likely related to alterations
      in follicular growth and maturation. The physiological mechanisms by which
      information on the metabolic changes is transmitted to the hypothalamus-pituitary
      ovary axis are not fully understood in the sow. Glucose, insulin and leptin are
      the most likely signals informing the hypothalamus of the metabolic state, yet
      their roles have not been definitely established. At the ovarian level,
      folliculogenesis is likely to be altered by the reduction in insulin and IGF-I
      concentrations induced by nutritional deficiency. More knowledge is needed at the
      intrafollicular level to better understand nutritional effects on follicular
      development, and also on occyte quality and embryo development.

PMID- 19848277
TI  - Appearance, fate and utilization of abnormal porcine embryos produced by in vitro
      maturation and fertilization.
AB  - In vitro production (IVP) including in vitro maturation (IVM) and fertilization
      (IVF) is now an important technology for obtaining live piglets. However, there
      are still two significant obstacles to the efficient production of viable porcine
      embryos: (1) polyspermy and (2) fertilization of oocytes arrested at the immature
      stage. These phenomena relate to production of embryos with abnormal ploidy
      (polyploidy). To avoid these problems, careful selection of mature oocytes for
      IVF, and regular monitoring of normal and abnormal fertilization (polyspermy
      and/or lack of male pronucleus formation) are very important. In our recent
      studies, however, we have confirmed that some oocytes with abnormal ploidy after
      polyspermy can develop into diploid embryos with potentially normal developmental
      ability. The mechanism by which such fertilized polyploid oocytes develop to a
      normal state during embryo development is still not well understood. Attempts to
      clarify this mechanism would hopefully reveal data that are very useful for not
      only IVP but also other technologies such as the production of transgenic or
      cloned animals using IVM oocytes, including other species, also for human
      reproductive manipulation. In this review, we focus on studies of normality of
      IVM oocytes and ploidy of IVP embryos, and try to suggest practical ways of
      solving the problems mentioned above in pigs.

PMID- 19848278
TI  - Intra-follicular regulatory mechanisms in the porcine ovary.
AB  - The mechanisms controlling the follicular growth continuum in the pig involve the
      interaction between local growth factors which are expressed throughout
      development and extra-follicular factors such as gonadotrophins. A large number
      of follicular growth factors, many belonging to the transforming growth factor
      beta (TGF-beta) superfamily, have been identified in the somatic cells and in the
      oocyte. The relative importance of these intra-follicular factors varies with
      stage of development. The initiation of follicular growth and early preantral
      development is controlled locally (by factors including c-kit-kit ligand, members
      of the bone morphogenetic family (e.g BMP-15) and growth differentiation factor-9
      (GDF-9)) and gonadotrophins are not thought to be involved until later. During
      antral follicle development, the oocyte secretes factors that stimulate porcine
      granulosa cell proliferation and differentiation, modulate apoptosis and suppress
      progesterone production, thereby preventing premature luteinisation. Likely
      candidates for mediating these effects include BMP-6, -15 and GDF-9 that are
      critical for fertility and ovulation rate in several mammals. There are also
      paracrine interactions between the somatic cells, with theca derived transforming
      growth factor beta (TGF-beta) playing a key role in regulating antral follicle
      maturation. Finally, during the periovulatory period, members of the EGF family
      from the granulosa cells stimulate cumulus expansion and oocyte maturation.
      Evidence indicates that some of these local factors may also influence oocyte
      developmental potential, emphasizing further the complexity, and importance, of
      these intra-follicular interactions.

PMID- 19848280
TI  - Ovarian responses to lactation management strategies.
AB  - A number of lactation management strategies can be applied to reduce negative
      effects of lactation on post-weaning fertility. This paper focuses on effects of
      lactation length, Intermittent Suckling and Split Weaning on follicle development
      and subsequent oestrus. It is concluded that a lactation length of less than 3
      weeks still leads to suboptimal reproductive performance in our modern sows.
      Further, both Intermittent Suckling and Split Weaning stimulate lactational
      follicle development and oestrus, but the variation in response between sows
      still limits practical application.

PMID- 19848281
TI  - Studies on fixed-time ovulation induction in the pig.
AB  - A technology that allows for manipulating of oestrus and ovulation, and would
      then also allow for fixed-time insemination, can be of great benefit for swine
      farms that operate using sow batch management due, at least in part, to savings
      in labour and the production of large batches of evenly developed pigs. Thanks to
      the current knowledge on endocrine regulation of follicle development and
      ovulation, and the availability of numerous reproductively active substances such
      a technology is now available. It covers procedures for synchronising oestrus
      based on the use of altrenogest in gilts and of batch-wise weaning in sows, for
      stimulating follicle development using eCG and for inducing of ovulation using
      hCG or LH as well as GnRH analogues. While the procedures for oestrus
      synchronisation stand alone, other procedures require additional treatments. If
      fixed-time insemination is the goal, oestrus needs to be synchronised and
      follicular development and ovulation induced by the use of GnRH analogues and hCG
      with ovulation occurring within 36-42 hrs. It is a general recommendation to
      inseminate those animals twice, i.e. 24 and 40 hrs after ovulation induction.
      However, the aforementioned technology requires healthy animals and a solid
      management and cannot be used to compensate for poor management.

PMID- 19848279
TI  - Transcriptional, post-transcriptional and epigenetic control of porcine oocyte
      maturation and embryogenesis.
AB  - Embryogenesis is a complex process that is controlled at various levels. As new
      discoveries are made about molecular mechanisms that control development in other
      species, it is apparent that these same mechanisms regulate pig embryogenesis as
      well. Methylation of DNA and modification of histones regulate transcription, and
      mechanisms such as ubiquitinization, autophagy and microRNAs regulate development
      post-transcriptionally. Each of these systems of regulation is highly dynamic in
      the early embryo. A better understanding of each of these levels of regulation
      can provide tools to potentially improve the reproductive process in pigs, to
      improve methods of creating pig embryos and cloned embryos in vitro, and to
      provide markers for predicting developmental competence of the embryo.

PMID- 19848282
TI  - Post-weaning altrenogest treatment in primiparous sows; the effect of duration
      and dosage on follicular development and consequences for early pregnancy.

PMID- 19848283
TI  - Assessment of follicle population changes in sows from day of weaning and during
      estrus using real-time ultrasound.

PMID- 19848284
TI  - Temporal candidate gene expression patterns in the sow placenta during early
      gestation and the effect of maternal L-arginine supplementation.

PMID- 19848285
TI  - Estrogen and interleukin-1beta regulation of trophinin, osteopontin,
      cyclooxygenase-1, cyclooxygenase-2, and interleukin-1beta system in the porcine
      uterus.

PMID- 19848286
TI  - Proteomic study to identify factors in follicular fluid and/or serum involved in
      in vitro cumulus expansion of porcine oocytes.

PMID- 19848287
TI  - Impact of selection for uterine capacity on the placental transcriptome.

PMID- 19848288
TI  - Enrichment of porcine spermatogonia by differential culture.

PMID- 19848289
TI  - Cloning and expression of pluripotent factors around the time of gastrulation in
      the porcine conceptus.

PMID- 19848290
TI  - Prenatal programming of postnatal development in the pig.
AB  - Studies of low birth weight offspring have a long history in pig science. These
      pigs have reduced growth potential and poor carcass quality compared to their
      higher birth weight littermates. In contemporary commercial sows with between 10
      and 15 total pigs born/litter, between-litter differences in average birth weight
      appear to make the largest contribution to variation in postnatal growth
      performance, independent of numbers born. Low birth weight is a characteristic of
      a subpopulation of these sows, likely as a consequence of an imbalance between
      ovulation rate and uterine capacity due to ongoing selection for litter size.
      Based on experimental studies, we hypothesize that increased crowding at day 30
      of gestation primarily affects placental development and persistent negative
      impacts on placental growth then affect fetal development. However, embryonic
      myogenic gene expression is already affected at day 30. Latent effects of
      metabolic state on oocyte quality and early embryonic development have also been
      reported. In contrast to effects of uterine crowding, the embryo is primarily
      affected by previous catabolism. The large body of literature on gene imprinting,
      and the interactions between metabolism, nutrition, and methylation state,
      suggest that classic imprinting mechanisms may be involved. However, the
      potential use of genomics, epigenomics, nutrigenomics, and proteomics to
      investigate these mechanisms brings new demands on experimental design and data
      management that present a considerable challenge to the effectiveness of future
      research on prenatal programming in the pig.

PMID- 19848291
TI  - Cellular and molecular events in early and mid gestation porcine implantation
      sites: a review.
AB  - Commercial, North American pork breeds (Sus scrofa) experience significant loss
      of genetically-normal conceptuses during the peri-implantation (attachment)
      period and at mid-gestation (day 50 to 90 of the 114 day porcine gestation
      interval). Although exact causes for these losses are not defined, asynchronous
      in-utero development and deficits in vascularization of the endometrium and
      placenta appear to be involved. Understanding of normal maternal-fetal dialogue
      is critical to develop breeding or therapeutic strategies that improve fetal
      health and overall litter size in commercial pigs. The non-invasive,
      epitheliochorial porcine placenta permits investigation of maternal or fetal
      compartments without cross contaminating cells. We developed and use protocols to
      capture single, homogenous populations of porcine cells (endometrial lymphocytes,
      dendritic or endothelial cells) from histological sections using laser capture
      microdissection (LCM), a powerful tool for study of gene expression that reflects
      the in vivo environment. These data are compared with gene expression in biopsies
      of endometrium and of trophoblast from the same, attachment sites. Here we review
      justifications for selection of the genes we have studied and our published and
      in progress work. These data provide new insights into the roles of the
      endometrial immune environment in the regulation of the success and failure of
      porcine conceptuses.

PMID- 19848292
TI  - Functional genomic approaches for the study of fetal/placental development in
      swine with special emphasis on imprinted genes.
AB  - This chapter describes the application of functional genomic approaches to the
      study of imprinted genes in swine. While there are varied definitions of
      "functional genomics", in general they focus on the application of DNA
      microarrays, single nucleotide polymorphism (SNP) arrays, and other high coverage
      genomic analyses, and their combination with downstream methods of gene
      modification such as silencing RNA (siRNA) and viral and non-viral transfection.
      Between the initial data acquisition and the actual genetic manipulation of the
      system lies bioinformatics, where massive amounts of data are analyzed to extract
      meaningful information. This area is in constant flux with an increased emphasis
      on detection of affected pathways and processes rather than generation of simple
      affected gene lists. We will expand on each of these points and describe how we
      have used these technologies for the study of imprinted genes in swine. First we
      will introduce the biological question to provide context for the discussion of
      the functional genomic approaches and the types of information they generate.

PMID- 19848293
TI  - Development of the pig placenta.
AB  - Placental insufficiency results in fetal loss, low birth weight, stillbirth,
      preweaning mortality and poor growth. Placental development begins at conceptus
      elongation, which is a primary factor controlling the size of the placenta. After
      elongation, the allantois develops outward from the embryo to establish the
      allantochorion, which defines the size of the functional placenta. During
      implantation, chorionic trophoblasts adhere to endometrial epithelial cells.
      Placental structures known as areolae develop at the openings of the endometrial
      glands and take up endometrial gland secreted products (histotrophe). Between day
      30 and 35 of gestation, the adhered trophoblast-endometrial epithelial bilayer
      undergoes microscopic folding. Fetal and maternal capillaries develop adjacent to
      the bilayer and blood flows are arranged in a cross-countercurrent manner. Except
      for nutrients secreted by the glands, nutrient exchange takes place between these
      capillaries within these folds. By day 85, the folds deepen and become more
      complex, increasing surface area. The epithelial bilayer thins and capillaries
      indent the plane of each layer (but do not penetrate), reducing distance between
      capillaries. The folded bilayer is surrounded by endometrial stroma on the
      maternal side and placental stroma on the fetal side. The fetal-placental stroma
      is partially composed of glycosaminoglycans, the most abundant being hyaluronan
      and heparan sulfate. Changes in both hyaluronoglucosaminidase and heparanase
      during placental development suggest that these enzymes play a role in placental
      development. In addition to structural modifications, various nutrient specific
      transport mechanisms exist. These mechanisms are likely to be as important to
      transport of specific nutrients as placental size or structure.

PMID- 19848294
TI  - Growth, body state and breeding performance in gilts and primiparous sows.
AB  - Optimizing gilt management is a critical point to improve breeding herd
      efficiency. This review describes the effects of growth rate (GR) and body state
      at onset of puberty stimulation or at first mating on gilt puberty attainment,
      productivity and sow longevity. Traditional management practices should be re
      evaluated with attention to different modern genotypes. It is difficult to
      discern the real effects of age, weight, backfat depth and estrus number at first
      insemination on longevity and reproductive performance, because these variables
      affect one another. GR interacts with age at boar exposure to influence age at
      puberty. Higher lifetime GR gilts (>700 g/d) attain puberty earlier and have a
      lower anoestrus rate. If gilts attain a target weight (135-150 kg), are adapted
      to herd health status and have at least one previously recorded estrus, they can
      be inseminated. Overweight at first breeding and throughout gestation should be
      avoided. There is no advantage in breeding gilts heavier than 150 kg; at first
      farrowing the target weight is 180-185 kg. Piglet production at first parity may
      be increased in gilts with a high GR but the number of stillborn piglets can also
      be increased. The culling rate over 3 parities for locomotion problems, which is
      one of the major risk factors for reduced herd retention rate, can be increased
      in overweight gilts at first breeding (>150-170 kg).

PMID- 19848295
TI  - Genetic selection for lifetime reproductive performance.
AB  - Genetic improvement of sow lifetime reproductive performance has value from both
      the economic perspectives of pork producers and the pork industry, but also from
      the perspective of ethical and animal welfare concerns by the general public.
      Genetic potential for piglets produced from individual litters is a primary
      determinant of lifetime prolificacy, but females must be able to sustain
      productivity without injury or death beyond the achievement of positive net
      present value. Evidence exists for between- and within-line genetic variation in
      sow lifetime performance, suggesting that improvements may be made by both line
      choices and genetic selection within lines. However, some of the same barriers to
      accurate within-line selection that apply to individual litter traits also
      present challenges to genetic selection for sow lifetime prolificacy: generally
      low heritabilites, sex-limited expression, expression after the age that animals
      are typically selected, and unfavorable genetic correlations with other traits in
      the profit function. In addition, there is an inherent conflict within the
      genetic nucleus herds where selections take place between the goal of shortened
      generation interval to accelerate genetic progress and the expression of sow
      lifetime traits. A proliferation in the industry of commercial multipliers with
      direct genetic ties and routine record flows to genetic nucleus herds provides a
      framework for accurate estimates of relevant genetic variances and covariances,
      and estimation of breeding values for sow lifetime traits that can be used in
      genetic selection.

PMID- 19848296
TI  - Responses to exogenous gonadotrophin treatment in contemporary weaned sows.

PMID- 19848297
TI  - Benefits of synchronizing ovulation with porcine luteinizing hormone (pLH) in a
      fixed time insemination protocol in weaned multiparous sows.

PMID- 19848298
TI  - Antiluteolytic mechanisms and the establishment of pregnancy in the pig.
AB  - Extended exposure of progesterone and conceptus estrogen influences the vascular
      compartment of the uterus and expression of many factors, such as prostaglandins
      (PGs), growth factors, extracellular matrix and adhesion molecules, cytokines and
      transcription factors. One of the supportive mechanisms by which the conceptus
      inhibits luteolysis is by changing PG synthesis in favor of luteoprotective PGE2.
      Alteration in PG synthesis may result from increased PGE synthase (mPGES-1)
      expression in the trophoblast and endometrium on days 10-13 of pregnancy with
      simultaneous down-regulation of PGF synthase (PGFS) and prostaglandin 9
      ketoreductase (CBR1). Conceptus and endometrial, rather than luteal, synthesis of
      PGE2, is involved in the process of maternal recognition of pregnancy. However,
      complex (direct and indirect) actions of estrogen on the CL, including decreased
      luteal VEGF soluble receptor on day 12 of pregnancy, are important for luteal
      maintenance. Moreover, conceptus signals affect another lipid signaling component
      - lysophosphatidic acid receptor (LPA3), as well as HoxA10 and Wnt in the
      endometrium, to create the appropriate uterine environment for establishment of
      pregnancy and implantation.

PMID- 19848299
TI  - Conceptus-uterus interactions in pigs: endometrial gene expression in response to
      estrogens and interferons from conceptuses.
AB  - This review highlights information on conceptus-uterus interactions in the pig
      with respect to uterine gene expression in response to estrogens and interferons
      (IFNs) secreted from elongating conceptuses. Pig conceptuses release estrogens
      for pregnancy recognition, but also secrete IFNs that do not appear to be
      antiluteolytic. Estrogens and IFNs induce expression of largely non-overlapping
      sets of genes, and evidence suggests that pig conceptuses orchestrate essential
      events of early pregnancy including pregnancy recognition signaling, implantation
      and secretion of histotroph by precisely controlling temporal and spatial (cell
      specific) changes in uterine gene expression through initial secretion of
      estrogens, followed by cytokines including IFNG and IFND. By Day 12 of pregnancy,
      estrogens increase the expression of multiple genes in the uterine luminal
      epithelium including SPP1, STC1, IRF2 and STAT1 that likely have roles for
      implantation. By Day 15 of pregnancy, IFNs upregulate a large array of IFN
      responsive genes in the underlying stroma and glandular epithelium including
      ISG15, IRF1, STAT1, SLAs and B2M that likely have roles in uterine remodeling to
      support placentation.

PMID- 19848300
TI  - Effect of progesterone antagonist RU486 on uterine progesterone receptor mRNA
      expression, embryonic development and ovarian function during early pregnancy in
      pigs.

PMID- 19848301
TI  - Select nutrients and glucose transporters in pig uteri and conceptuses.

PMID- 19848302
TI  - [The Revista de Investigacion Clinica and the National Institutes of Health].

PMID- 19848303
TI  - Hypertension as a risk factor for developing depressive symptoms among community
      dwelling elders.
AB  - OBJECTIVE: To determine whether hypertension (HTA) is an independent predictor of
      depressive symptoms (DS) in a sample of elderly Mexican community-dwelling
      persons. MATERIAL AND METHODS: Two-year longitudinal study of 3,276 community
      dwelling persons aged 60 years and older, participating in the Mexican Health and
      Aging Study. Subjects that self-reported both having or not having HTA while
      denying DS at baseline were included. Two-year follow-up data were analyzed, and
      multiple regression analyses were used to test whether HTA is an independent
      predictor of incident DS after adjusting for many potential confounders. RESULTS:
      Mean age of participants was 68.4 +/- 6.9 years. Prevalence of HTA was 36.6%. At
      follow-up, 28.7% developed DS. After adjusting for multiple covariates (age, sex,
      education level, relationship status, self-reported health and economic status,
      diabetes, arthritis, stroke, ischemic cardiopathy, falls, pain, hearing
      impairment, visual impairment, urinary incontinence, cognitive impairment,
      smoking, alcohol use, and baseline disability), HTA was an independent predictor
      of DS at two years followup (Adjusted Odds Ratio = 1.18; 95% confidence interval
      = 1.01-1.40). CONCLUSIONS: Hypertension is an independent risk factor for the
      development of depressive symptoms. Programs to support early treatment of
      cardiovascular disease and hypertension should be implemented in order to prevent
      late-onset of depressive symptoms.

PMID- 19848304
TI  - [Diabetic foot microbiology through biopsy cultures].
AB  - OBJECTIVE: To determine the microbiology of diabetic foot wounds, through biopsy
      cultures. MATERIALS AND METHODS: Patients with diabetic foot and clinical data of
      infection were recruited consecutively. Cultures were processed for aerobic
      organisms after mortar homogenization. For cases with multiple isolates, only the
      two predominant organisms were identified. The bacterial identification was
      carried out by biochemical procedures. The sensitivity to antibiotics was made by
      the disk diffusion method. RESULTS: A total of 91 biopsies were studied, 47 from
      men (52%). There were 102 isolates, 68 being Gram-negative bacilli (67%), with
      predominance of Escherichia coli (21%). A total of 28 Gram-positive cocci were
      isolated (28%) and 6 yeasts (6%). Of the 68 Gram-negative bacilli, 24 were
      resistant to ciprofloxacin (35%). A total of 55 Enterobacteriaceae were isolated,
      of which 4 (7%) produced extended-spectrum beta-lactamases. There were 8
      Staphylococcus aureus isolates, 3 of which (38%) were resistant to methicillin.
      CONCLUSIONS: In comparison with reports from industrialized countries, we found a
      higher proportion of Gram-negative and resistant organisms.

PMID- 19848305
TI  - [Prevalence and associated factors related to disordered eating in student
      adolescents of Guadalajara across sex].
AB  - OBJECTIVE: To determine the prevalence and associated factors to disordered
      eating (DE) in adolescents by sex. MATERIAL AND METHODS: A transversal and
      analytic study was carried out with 1,134 first grade students at a public high
      school. Self esteem, impulsivity, depressive symptoms, suicidal ideation,
      entertainment, locus of control, relationship with father/ mother, stress and DE
      were assessed with previously validated and standardized scales. RESULTS: A
      prevalence of 7.2% of risky eating behaviors was obtained; 2.8% for men and 10.3%
      for women. In men in the risk analysis the association was maintained for
      impulsivity, depressive symptoms, suicidal ideation and stress. After the
      multivaried analysis only depression and stress showed any association. In women
      in the risk analysis, the association was maintained for impulsivity, depressive
      symptoms, suicidal ideation and stress, and after the multivaried analysis only
      impulsivity, suicidal ideation and stress maintained the association.
      CONCLUSIONS: The prevalence of DE was higher among women. The associated factors
      in men were depressive symptoms and stress, whilst for women was impulsivity,
      suicidal ideation and stress.

PMID- 19848306
TI  - [Yeast susceptibility isolated from blood cultures of patients at the National
      Cardiology Institute Ignacio Chavez].
AB  - INTRODUCTION: With the increasing prevalence of bloodstream infections caused by
      Candida sp. is necessary to establish the susceptibility of resistant strains in
      various geographical regions. OBJECTIVE: To determine the in vitro susceptibility
      to fluconazole, itraconazole, voriconazole and amphotericin B in yeasts isolated
      from blood through E test method. MATERIAL AND METHODS: In the period from 1992
      to 2007, a total 112 strains of Candida species were isolated from blood of
      patients at the National Institute of Cardiology Ignacio Chavez. Susceptibility
      of these strains was performed to know the level of resistance to Itraconazole,
      Fluconazole, Voriconazole and Amphotericine B by E test method. RESULTS: C.
      albicans was the most common species (60.2%), followed by C. tropicalis (9.8%). A
      five percent of resistance to itraconazole, 1.8% to fluconazole; and 0.9% to
      amphotericine B and voriconazole were found. C. glabrata was the most resistant
      species to the four antifungal agents. CONCLUSION: The yeasts resistance to the
      four antifungal agents is still lower in our patients.

PMID- 19848307
TI  - Dental caries and risk factors in adolescents of Ecatepec in the State of Mexico.
AB  - OBJECTIVE: To identify the prevalence of dental caries and to evaluate the risk
      cariogenic factors in adolescents of the State of Mexico. MATERIAL AND METHODS:
      An observational, descriptive and transversal study was conducted. The sample
      consisted of 109 teenagers, with ages ranging from 14 to 16 years old, 50 male
      and 59 female. Their teeth were evaluated using the DMFS index (decayed, lost and
      filled on the surface); the study was conducted by a WHO criteria standardized
      dentist researcher, with an intraexaminator Kappa value of 0.96. A survey was
      also conducted to establish the risk factors related to dental caries. RESULTS:
      The DMFS results found were of 4.05 +/- 3.47. In males the DMFS was of 3.50 +/-
      3.56 with the following distribution: DS 3.22 +/- 3.54, MS 0.10 +/- 0.58 y FS
      0.18 +/- 0.72, while with females the DMFS was of 4.51 +/- 3.35, DS 3.86 +/-
      3.21, MS 0.15 +/- 0.61 and FS 0.51 +/- 1.19. Dental caries is related to the
      following variables: gender, frequency of toothbrushing, attendance to the
      dentist and intake of sugared products. CONCLUSIONS: It is recommended to
      continue with the health promotion programs, as well as with the use of
      fluoridated products, emphasizing tooth brushing and a decrease in the intake of
      sugared products.

PMID- 19848308
TI  - Rapid detection of ESBL-producing gram-negative bacteria isolated from blood: a
      reasonable and reliable tool for middle and low resource countries.
AB  - INTRODUCTION: Delay in appropriate treatment in patients with bacteraemia can
      increase morbidity, mortality, and health expenditures. We compared the Rapid
      Direct Test (RDT) designed to detect ESBL-producing gram-negative bacteria (GNB)
      directly from positive blood cultures bottles, with two conventional ESBL
      detection tests: Screening and Confirmatory Disk Diffusion Assay (SC-DDA) and an
      MIC Screening and ESBL E-test (MIC/ET). MATERIAL AND METHODS: We screened all
      blood cultures in a tertiary care facility from August to December 2005. We only
      included one positive bottle per patient in which GNB were observed. RDT: Blood
      from each bottle was inoculated on Mueller-Hinton agar. Ceftazidime and
      cefotaxime disks with and without clavulanic acid were added and incubated at 35
      degrees C +/- 2 degrees C for 24 h. Results were interpreted according to CLSI
      recommendations for the SC-DDA and MIC/ET. All methods were performed
      simultaneously. Time for reporting as an ESBL-producer and cost of the tests were
      recorded. RESULTS: We isolated 124 GNB in 114 episodes of bacteraemia, 10 of them
      (8.8%) polymicrobial; 79 (63.7%) of the GNB were enteric bacteria, 44 (35.5%)
      glucose non-fermenter GNB and one Haemophilus influenzae. The most common
      microorganism was Escherichia coli in 56 episodes (45.2%), followed by
      Pseudomonas aeruginosa in 24 (19.3%), and Klebsiella pneumoniae in 13 (10.5%). Of
      the 114 episodes, 41 (36%) had at least one GNB resistant to 3rd generation
      cephalosporins, and 25 (21.9%) were caused by an ESBL-producing GNB. Sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      for the RDT were 96%, 98.9%, 96% and 98.9%, respectively. Agreement by kappa
      index between RDT and SC-DDA was 0.95 and between the RDT and MIC/ET was 0.92.
      The RDT detected 24/25 ESBL-producing bacteria. The mean time to detect an
      isolate as an ESBL producer after a positive blood culture bottle signal was 1.02
      +/- 0.19 days when using the RDT, and 3.40 +/- 0.59 days when using any other
      method. The difference in reporting time was 2.38 +/- 0.63 days (p < 0.0001). Our
      estimated cost per test was $1.54 for RDT, $2.32 for screening/ confirmatory SC
      DDA, and $49.65 for MIC screening and MIC/ET. Conclusions. The RDT is a rapid,
      reliable and easy analysis to perform, as well as cost-effective.

PMID- 19848309
TI  - [Fc receptor functions in host and immune regulation].
AB  - Specific receptors for antibody, named Fc Receptors are proteins found on the
      surface of leukocytes. Fc receptors contribute to the protective functions of the
      immune system, by binding to antibodies that are attached to infected cells or
      invading pathogens. Fc receptor activity stimulates phagocytic or cytotoxic cells
      to destroy microbes, or infected cells by antibody-mediated phagocytosis or
      antibody-dependent cell-mediated cytotoxicity. This review describes the main
      types of Fc receptors and the signal transduction pathways that are initiated by
      them in various leukocytes, with emphasis on activation of phagocytosis. New
      findings on the regulatory role of Fc receptors on immune function are also
      discussed.

PMID- 19848310
TI  - [Inflammaging. Aging inflammatory origin].
AB  - The association between the increase in life expectancy in humans and age-related
      changes in the immune system promotes that individuals are exposed longer to
      endogenous and environment antigens which allows an activation of the innate
      immune system and the subsequent establishment of a low grade chronic
      inflammation state with an increased expression of proinflammatory cytokines
      (tumor necrosis factor alpha, interleukin 6, etc.). This inflammatory state
      referred as inflammaging is characterized by a inflammatory origin of aging given
      by the activation of cellular systems responsible of gene promotion and
      suppression as the nuclear factor kappa B, sirtuins, forkhead box O and KLOTHO,
      who are directly or indirectly involved in cellular mechanisms of resistance to
      oxidative stress, apoptosis and nucleic acids transcriptional mistakes repair.
      The activation of these cellular systems is associated with the pathogenesis of
      several chronic and degenerative diseases such as Alzheimer's disease, late-onset
      diabetes or cardiovascular diseases. However, we are placed in a crossroad
      because we can not establish whether this inflammatory state observed in the
      aging process is responsible of development of degenerative diseases or if the
      presences of these chronic diseases are responsible for this inflammatory state
      of aging. Evidence in centenarians who are healthy and have preserved functional
      status has shown that there is a chronic inflammatory state present among them
      but is balanced by a higher expression of anti-inflammatory molecules.

PMID- 19848311
TI  - [Obesity and metabolic syndrome. A challenge for the Mexican Institutes of
      Health].
AB  - Numerous efforts for the development of basic and clinical research in obesity
      are being made by the National Institutes of Health and Federal Reference
      Hospitals in Mexico. However, greater interaction among researchers and stronger
      efforts towards the dissemination of the results are needed. The document
      outlines the general ideas and proposals of the Academic Group for the Study,
      Prevention and Treatment of Obesity and Metabolic Syndrome of the Coordinating
      Committee of the National Institutes of Health and High Specialty Hospitals
      (CCINSHAE). This is the first step in developing common objectives, with the aim
      of understanding the effect of these entities in public health and to establish
      guidelines to limit and eventually overcome them. We discuss the appropriateness
      of analyzing obesity and the metabolic syndrome together, and the current
      management of these entities at the National Institutes of Health in Mexico. The
      problems that arise in clinical practice lead to the need to generate a new model
      of medical care, including a new health worker and a new patient. It is
      imperative to establish permanent lines of communication and education with
      health personnel and with patients. The group proposes an integrated approach for
      research in these areas. Finally, a master plan that links the National
      Institutes of Health, particularly in the areas of research and programs within
      the institutions, is required as a first step in seeking answers useful in
      solving the problem. The second step would be linking the first and second levels
      of care through concrete actions needed to limit and reduce obesity and metabolic
      syndrome in the population.

PMID- 19848312
TI  - Sevoflurane versus propofol for myocardial protection in patients undergoing
      coronary artery bypass grafting surgery: a meta-analysis of randomized controlled
      trials.
AB  - OBJECTIVE: To systematically review randomized controlled trials to compare
      myocardial protection profiles of sevoflurane with propofol in patients
      undergoing coronary artery bypass grafting (CABG) surgery. METHODS: Electronic
      databases were searched to identify all randomized controlled trials comparing
      sevoflurane with propofol for protecting myocardium in adult patients undergoing
      CABG surgery. Two authors independently extracted patients' perioperative data,
      including patients' baseline characteristics, surgical variables, and outcome
      data. For continuous variables, treatment effects were calculated as weighted
      mean difference (WMD) and 95% confidential interval (CI). For dichotomous data,
      treatment effects were calculated as odds ratio (OR) and 95% CI. Each outcome was
      tested for heterogeneity, and randomized-effects or fixed-effects model was used
      in the presence or absence of significant heterogeneity (Q test P<0.05).
      Sensitivity analyses were done by examining the influence of statistical model on
      estimated treatment effects. Publication bias was explored through visual
      inspection of funnel plots of the outcomes. Statistical significance was defined
      as P<0.05. RESULTS: Our search yielded 13 studies including 696 patients, and 402
      patients were allocated into sevoflurane group and 294 into propofol group. There
      was no significant difference in postoperative mechanical ventilation time,
      inotropic support, mortality, myocardial infarction, and atrial fibrillation
      between the two groups (all P>0.05). Patients randomized into sevoflurane group
      had higher post-bypass cardiac index (WMD=0.39, 95% CI: 0.18 to 0.60, P=0.0003),
      lower troponin I level (WMD=-0.82, 95% CI: -0.87 to -0.85, P=0.0002), lower
      incidence of myocardial ischemia (OR=0.37, 95% CI: 0.16 to 0.83, P=0.02), shorter
      ICU and hospital stay length (WMD=-10.99, 95% CI: -12.97 to -9.01, P<0.00001;
      WMD=-0.78, 95% CI: -1.00 to -0.56, P<0.00001, respectively). CONCLUSION: This
      meta-analysis has found some evidence showing that sevoflurane has better
      myocardial protection than propofol in CABG surgery.

PMID- 19848313
TI  - Prevalence of abnormity of blood lipid and associated factors in health
      examination population in Beijing.
AB  - OBJECTIVE: To investigate the prevalence of abnormity of blood lipid and
      associated factors in healthy population in Beijing. METHODS: Totally, 38462
      individuals who received health examination were enrolled in our study. We
      divided them into eight groups according to their ages. The levels of serum total
      cholesterol, triglyceride, high density lipoprotein cholesterol, and low density
      lipoprotein cholesterol were tested, and the relationship of blood lipid
      abnormity with body mass index (BMI) and fasting blood glucose was analyzed.
      RESULTS: The incidences of hypercholesterolemia, hyperglyceridemia, low high
      density lipoprotein cholesterolemia, and hyper low-density lipoprotein
      cholesterolemia presented increasing trend in this population. The incidence rate
      of abnormity of blood lipid in health examination population increased with BMI
      increase. The incidence of abnormity of blood lipid in overweight and obesity
      population was significantly higher than that in low weight and normal weight
      populations (P<0.05). Meanwhile, the trend of abnormal blood lipid incidence
      coincided with that of abnormal fasting blood glucose. CONCLUSIONS: The
      prevalence of overweight, obesity, and abnormity of blood lipid in Beijing
      presents increasing trend. The incidence of abnormity of blood lipid increases
      with BMI increase, in coincidence with that of fasting blood glucose.

PMID- 19848314
TI  - Pregnancy outcomes of repeat cesarean section in Peking Union Medical College
      Hospital.
AB  - OBJECTIVE: To evaluate the effect of elective repeat cesarean section on the
      maternal and neonatal outcomes. METHODS: A retrospective clinic- and hospital
      based survey was designed for comparing the maternal and neonatal outcomes of
      elective repeat cesarean section [RCS group (one previous cesarean section) and
      MRCS group (two or more previous cesarean sections)] and primary cesarean section
      (FCS group) at Peking Union Medical College Hospital from January 1998 to
      December 2007. RESULTS: The incidence of repeat cesarean section increased from
      1.26% to 7.32%. The mean gestational age at delivery in RCS group (38.1+/-1.8
      weeks) and MRCS group (37.3+/-2.5 weeks) were significantly shorter than that in
      FCS group (38.9+/-2.1 weeks, all P<0.01). The incidence of complication was 33.8%
      and 33.3% in RCS group and MRCS group respectively, and was significantly higher
      than that in FCS group (7.9%, P<0.05). Dense adhesion (13.5% vs. 0.4%, OR=7.156,
      95% CI: 1.7-30.7, P<0.01) and uterine rupture (1.0% vs. 0, P<0.05) were commoner
      in RCS group compared with FCS group. Neonatal morbidity was similar among three
      groups (P>0.05). CONCLUSIONS: Repeat cesarean section is associated with more
      complicated surgery technique and increased frequency of maternal morbidity.
      However, the incidence of neonatal morbidity is similar to primary cesarean
      section.

PMID- 19848315
TI  - 5-aminolaevulinic acid-photodynamic therapy for the treatment of cervical
      condylomata acuminata.
AB  - OBJECTIVE: To investigate the efficacy and safety of photodynamic therapy (PDT)
      with topical 5-aminolaevulinic acid (ALA) on cervical condylomata acuminata.
      METHODS: Patients with cervical condylomata (n=30) were allocated into primary
      and recurrent group, and were given topical ALA under occlusive dressing for 3
      hours followed by irradiation with semiconductor laser at a dose of 100 Jcm(-2)
      and a power of 100 mW. The treatment was repeated 7 days later if the lesion was
      not completely removed after the first treatment. Complete response rate and
      recurrence rate of wart lesions as well as rate of adverse reaction were
      analyzed. RESULTS: The total complete response rate of PDT was 100% and the total
      recurrence rate was 5% after 3 months of follow-up. Recurrence rate of recurrent
      group was significantly lower than that of prior managements (100%, P<0.01). The
      side effects of PDT in patients mainly included mild burning and/or stinging
      restricted to the illuminated areas, and was significant lower than their own
      control (25% vs. 100%, P<0.05). CONCLUSION: Compared with conventional therapies,
      topical application of ALA-PDT is a simple, effective, safe, well-tolerated, and
      low recurrence rate treatment for cervical condylomata acuminata.

PMID- 19848316
TI  - Assessment of coronary stents by 64-slice computed tomography: in-stent lumen
      visibility and patency.
AB  - OBJECTIVE: To assess lumen visibility of coronary stents by 64-slice computed
      tomography (CT) coronary angiography, and determine the value of 64-slice CT in
      non-invasive detecting of in-stent restenosis after coronary artery stent
      implantation. METHODS: Totally, 60 patients (54 males, aged 57.0+/-12.7 years)
      and 105 stents were investigated by 64-slice CT at a mean interval of 20.0+/-16.6
      months after coronary stents implantation. Axial multi-planar reconstruction
      images of the stents and curved-planar reconstruction images through the median
      of the stents were reconstructed for evaluating stent image quality on a 5-point
      scale (1=excellent, 5=non-assessable), and stent lumen diameter was detected.
      Conventional coronary angiography was performed in 18 patients, and 32 stents
      were evaluated. RESULTS: Image quality was good to excellent on average (score
      1.71+/-0.76). Stent image quality score was correlated to heart rate (r=0.281,
      P<0.01) and stent diameter (r=-0.480, P<0.001). All the stents were assessable in
      lumen visibility with an average visible lumen diameter percentage of 60.7%+/
      13.6%. Visible lumen diameter percentage was correlated to heart rate (r=-0.193,
      P<0.05), stent diameter (r=0.403, P<0.001), and stent image quality score (r=
      0.500, P<0.001). Visible lumen diameter percentage also varied depending on the
      stent type. In comparison with the conventional coronary angiography, 4 of 6 in
      stent stenoses were correctly detected. The sensitivity and specificity for the
      detection of in-stent stenosis were 66.7% and 84.6%, respectively. CONCLUSIONS:
      Using a 64-slice CT, the stent lumen is partly visible in most of the stents. And
      64-slice CT may be useful in the assessment of stent patency.

PMID- 19848317
TI  - High serum resistin level may be an indicator of the severity of coronary disease
      in acute coronary syndrome.
AB  - OBJECTIVE: To investigate the correlation between serum resistin level,
      cardiovascular risk factors and severity of coronary disease in acute coronary
      syndrome (ACS). METHODS: After evaluated by clinical history,
      electrocardiography, exercise tolerance tests, laboratory tests, and coronary
      angiography, 220 consecutive patients with suspected chest pain were divided into
      normal control group, stable angina pectoris (SAP) group, and ACS group,
      respectively. Baseline clinical characteristics, including height, weight, waist
      circumference, hip circumference, white blood cell count, high-sensitive C
      reactive protein (hsCRP), total cholesterol, triglyceride, low-density
      lipoprotein cholesterol and high-density lipoprotein cholesterol, were compared
      among three groups. ELISA was used to detect serum resistin levels. Pearson's
      correlation coefficient analysis was used to assess association between resistin
      and other traditional cardiovascular risk factors. Multinomial logistic
      regression analyses were used to define the relationship between serum resistin
      level and SAP or ACS. RESULTS: Serum resistin level in ACS group (1.18+/-0.48
      microg/L) was significantly higher than that in normal control and SAP groups
      (0.49+/-0.40 and 0.66+/-0.40 microg/L; P<0.01). Only in ACS group, increased
      serum resistin level was significantly correlated with hsCRP (r=0.262, P=0.004)
      and white blood cell count (r=0.347, P=0.001). Furthermore, serum resistin levels
      showed a stepwise increase with the number increase of > 50% stenosed coronary
      vessels. Multinomial logistic regression test demonstrated that serum resistin
      was a strong risk factor for ACS (OR=29.132, 95 % CI: 10.939-77.581, P<0.001).
      CONCLUSION: These findings suggested the potential role of resistin in
      atherosclerosis and especially its involvement in ACS.

PMID- 19848318
TI  - Lower extremity arterial occlusive disease as a rare complication of Crohn's
      disease.
AB  - OBJECTIVE: To investigate the clinical characteristics and treatment strategy of
      lower extremity arterial occlusive disease in patients with Crohn's disease (CD).
      METHODS: Clinical information of 9 cases suffering from lower extremity arterial
      occlusion and CD was investigated retrospectively. RESULTS: All the cases were
      less than 50 years old and the most were females (8/9). Arterial occlusions
      occurred in either active (5/9) or inactive (4/9) stage of CD. Besides the
      arteries of lower extremities, other arteries could also be involved such as
      aorta, iliac artery, renal artery or mesentery artery. Seven cases had
      atherosclerotic imaging findings (4 had aortic plaques and 6 had iliac artery
      stenoses). Embolectomy or thromboendarterectomy were mostly performed. Four
      (44.4%) cases had recurrent lower limb ischemia. CONCLUSIONS: Arterial occlusive
      disease is a rare extraintestinal manifestation of CD. A thorough inspection of
      aorta is necessary. Embolectomy is mostly preferred. Anticoagulation treatment is
      highly recommended after the operation.

PMID- 19848319
TI  - Single-stage posterior spondylectomy, circumferential decompression and
      reconstruction using mesh cage for spinal tumors.
AB  - OBJECTIVE: To explore the feasibility and clinical results of circumferential
      decompression and three-column reconstruction through single-stage posterior
      transpedicular approach for spinal tumor treatment. METHODS: Totally, 24 patients
      with spinal tumor underwent tumor resection and spinal reconstruction through
      single-stage posterior transpedicular approach. Preoperatively, according to the
      Frankel classification, 12 patients were grade E, 9 grade D, and 3 grade C.
      Anterior column was reconstructed with non-expandable titanium cages. Posterior
      segmental instrumentation was used to maintain the stability of spine in all
      cases. Anterior and posterolateral fusion was performed with autograft and
      allogenic bone. The following data were followed up in these patients: deformity
      angle, local recurrence, neurological function, and spinal bony fusion. RESULTS:
      The average operating time and blood loss was 5.6 hours and 3,400 ml
      respectively. No intraoperative and postoperative complications were observed in
      this group. Postoperatively, 21 patients were Frankel grade E, 2 grade D, and 1
      grade C. Four patients reported significant functional restoration and twenty
      patients reported complete resolution of pain. At follow-up (range, 6-42 months),
      implant failure or recurrent neurological symptoms was not found. CONCLUSIONS:
      The tumor resection and spinal reconstruction through single-stage posterior
      transpedicular approach is a safe and effective technique for the treatment of
      spinal tumor. It can fully decompress the neurological structures, correct the
      kyphosis, and achieve early weight-bearing. This technique can improve life
      quality for the patients with spinal tumor.

PMID- 19848320
TI  - Outcomes of CAG regimen for refractory biphenotypic acute leukemia patients.
AB  - OBJECTIVE: To evaluated the efficiency of low-dose cytosine arabinoside plus
      aclarubicin with concurrent administration of granulocyte colony-stimulating
      factor (CAG) regimen for refractory biphenotypic acute leukemia (BAL). METHODS:
      We treated 5 refractory BAL patients by CAG regimen (10 mg x m(-2) cytosine
      arabinoside subcutaneously administrated every 12 hours, day 1-14; 5-7 mg x m(-2)
      aclarubicin intravenously administrated daily, day 1-8; and concurrently used 200
      microg x m(-2) x d(-1) granulocyte colony-stimulating factor subcutaneously) from
      November 2002 to April 2007. The efficacy of the regimen was evaluated by
      response rate, and the side effects were also measured. RESULTS: The complete
      remission rate was 80%, median duration of absolute neutrophil count < 5.0 x
      10(8)/L and platelet count < 2.0 x 10(10)/L was day 13 and day 1, respectively;
      and the infection rate was low (III-IV infection rate, 20.00%). CONCLUSION: CAG
      regimen as remission induction chemotherapy for BAL patients is effective with a
      high remission rate and low toxicity.

PMID- 19848321
TI  - Hybrid endovascular aorta repair with simultaneous supra-aortic branch or iliac
      branch revascularization.
AB  - OBJECTIVE: To describe a hybrid endovascular procedure for aorta repair with
      different kinds of bypass followed by concomitant placement of stent graft in the
      aorta. METHODS: From June 2007 to May 2008, 5 consecutive patients who presented
      with aortic aneurysm or dissection were treated with a new hybrid aorta repair
      technique. Complete surgical rerouting of supra-aortic vessels was simultaneously
      created by endovascular repair of aortic arch aneurysm with stent graft. Hybrid
      left carotid-subclavian bypass with stent graft deployment covering the ostium of
      the left subclavian artery was performed in a Debakey type III aortic dissection
      case. The supra-aortic branch was revascularized in 2 cases from ascending aorta
      to bilateral common carotid arteries using a 16-8 mm bifurcated graft, then total
      aortic arch and descending artery was occluded with stent-graft. The left carotid
      artery to the left subclavian artery bypass was created in 1 case, followed by
      stent-graft deployment. Two cases of infrarenal abdominal aortic aneurysm
      underwent left external iliac artery to left internal iliac artery bypass by a
      retroperineal route, then hybrid procedure was performed with bifurcated stent
      graft. All stent grafts were deployed via a retrograde femoral artery approach in
      5 patients. RESULTS: Technical success with complete aneurysmal exclusion was
      achieved in all patients. There was no incidence of endoleak. During a follow-up
      period of 2 to 10 months, documented perioperative neurologic events did not
      occur in all patients. One patient suffered from adult respiratory distress
      syndrome. After received tracheostomy, he recovered later. There was one death
      resulting from a postoperative myocardial infarction. CONCLUSION: Hybrid arch
      repair provides an alternative therapy to patients otherwise considered
      prohibitively high risk for traditional open arch and thoracoabdominal aorta
      repair.

PMID- 19848322
TI  - Reinstate the damaged VEGF signaling pathway with VEGF-activating transcription
      factor.
AB  - OBJECTIVE: To investigate the role of vascular endothelial growth factor
      activating transcriptional factor (VEGF-ATF) on the VEGF signaling pathway in
      diabetes mellitus. METHODS: Totally, 20 C57BL/6 mice fed with high fat diet was
      induced into diabetes mellitus. Ten diabetes mellitus mice received a lower limb
      muscle injection with VEGF-ATF plasmid, and another ten were as control. VEGF-ATF
      is an engineered transcription factor designed to increase VEGF expression. Three
      days later, mice were sacrificed and the injected gastrocnemius was used for
      analysis. VEGF mRNA and protein expressions were examined by real-time PCR and
      ELISA respectively. VEGF receptor 2 mRNA expression was tested with RT-PCR.
      Phosphorylated Akt, Akt, endothelial nitric oxide synthase (eNOS), and
      phosphorylated eNOS were assessed by western blot. RESULTS: At 3 days post
      injection, in mice with diabetes mellitus, VEGF gene transfer increased VEGF mRNA
      copies and VEGF protein expression in injected muscles compared with control; and
      reinstated the impaired VEGF signaling pathway with increasing the ratios of
      phosphorylated Akt/Akt and phosphorylated eNOS/eNOS. However, it did not affect
      the expression of VEGF receptor 2 mRNA. CONCLUSION: Gene transfer with VEGF-ATF
      is able to reinstate the impaired VEGF downstream pathway, and potentially
      promote therapeutic angiogenesis in mice with diabetes mellitus.

PMID- 19848323
TI  - Abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail
      model induced by high fat diet.
AB  - OBJECTIVE: To establish abdominal fat accumulation with hyperuricemia and
      hypercholesterolemia quail model fed with high fat diet. And then to investigate
      the pathological characteristics of this quail model. METHODS: Thirty Longcheng
      quails were randomly divided into two groups: control group and model group
      (n=15). The control group quails were fed with normal diet and model group quails
      were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver
      and abdominal fat at euthanasia as well as serum were collected. The levels of
      serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C),
      low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA),
      and blood glucose were assayed. The activity changes of adenosine deaminase
      (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and
      fatty acid synthetase (FAS) were analyzed. RESULTS: Compared with control group,
      the abdominal fat content (0.74+/-0.63 vs. 1.36+/-0.65 g, P<0.05) and abdominal
      fat index (0.44%+/-0.30% vs. 0.85%+/-0.30%, P<0.01) as well as live lipid index
      (3.61%+/-0.65% vs. 11.33%+/-2.14%, P<0.01) in model group significantly
      increased; the levels of serum uric acid (210.61+/-94.76 vs. 304.25+/-141.94
      micromol/L, P<0.05), total cholesterol (4.20+/-0.51 vs. 20.10+/-11.25 mmol/L,
      P<0.01), LDL-C (1.16+/-0.29 vs. 10.78+/-6.48 mmol/L, P<0.01), and FFA (0.39+/
      0.14 vs. 0.55+/-0.15 mmol/L, P<0.01) in model group significantly increased; HDL
      C (5.85+/-0.95 vs. 4.14+/-2.03 mmol/L, P<0.05) significantly decreased; the
      levels of triglyceride and blood glucose had no significant changes (P>0.05); the
      activities of ADA (9.71+/-3.05 vs. 17.19+/-5.10 U/ml, P<0.01) and XOD (10.58+/
      6.88 vs. 19.22+/-9.44 U/L, P<0.01) in model group significantly increased; and
      FAS, LPL, HL had no significant changes (P>0.05). CONCLUSIONS: High fat diet can
      induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia
      quail model. The changes of uric acid and lipid metabolic enzyme activities may
      be the pathological mechanism of abdominal fat accumulation with hyperuricemia
      and hypercholesterolemia.

PMID- 19848324
TI  - [Progesterone receptor's profile and the effect of the hormone and its
      derivatives on invasiveness and MMP2 secretion in endometrial carcinoma cell
      lines].
AB  - INTRODUCTION: Progesterone inhibits endometrial proliferation and is used for the
      treatment of early stage endometrial carcinoma in women interested in fertility
      preservation or for advanced or recurrent disease. Better responses and prognosis
      were documented in women who are progesterone receptor positive. The receptor has
      2 main isoforms and the ratio between these two is responsible for progesterone
      activity OBJECTIVES: To evaluate the effect of progesterone and its derivative on
      invasion and matrix metalloproteinase 2 (MMP2) secretion in two endometrial
      carcinoma cell lines having different progesterone receptor isoform profiles.
      METHODS: HEC-1A and RL95-2 cell Line cultures were used. Tests for invasion using
      Matrigel and zymography for MMP secretion were conducted after the exposure of
      the cells to different derivatives of progesterone. RESULTS: RL95-2 cell are PR-A
      dominant and were found to be more invasive than HEC-1A which are PR-B dominant.
      After exposure to progesterone and medroxyprogesterone but not to
      hydroxyprogesterone invasion and MMP2 secretion were decreased significantly only
      in the HEC-1A cell line. CONCLUSION: PR-B dominance may predict better responses
      to progesterone therapy in women with endometrial carcinoma.

PMID- 19848325
TI  - [Correlation of maternal serum and amniotic fluid leptin and insulin levels with
      neonatal birth weight].
AB  - BACKGROUND: Numerous studies correlated maternal serum and fetal cord Leptin
      Levels in pregnancy with new born weight (NBW) and maternal body mass index
      (BMI). However, there are only a few published studies concerning amniotic fluid
      leptin and its possible relationship to fetal growth and NBW. OBJECTIVES: To
      correlate leptin and insulin in amniotic fluid and maternal serum collected at 16
      20 gestational weeks to NBW. METHODS: This was an observational study in which
      maternal serum Leptin, insulin, and amniotic fluid Leptin and insulin, studied
      from 70 healthy pregnant women undergoing amniocentesis for karyotyping, at 16-20
      weeks gestation. NBW was correlated with maternal BMI and leptin and insulin
      Levels in maternal serum and amniotic fluid. RESULTS: Maternal serum leptin was
      detected as the best predictor of NBW. Squared correlation coefficient, r2 =
      0.09, was statistically significant (P < 0.01). Maternal BMI correlated
      significantly with serum Levels of insulin and leptin r2 = 0.16 and 0.27
      respectively, P < 0.01. CONCLUSION: In normal pregnancies, amniotic fluid Leptin
      correlates partially with NBW. Maternal serum leptin correlates significantly
      with NBW.

PMID- 19848326
TI  - [Chronic pelvic pain and Allen-Masters syndrome].
AB  - Allen-Masters syndrome, first described at 1955, is considered an uncommon
      etiology for chronic pelvic pain. The syndrome associates traumatic delivery to
      lacerations found on the posterior leaf of the broad Ligament. The authors report
      the clinical and laparoscopic findings of a female patient who was admitted to
      their department for evaluation due to chronic pelvic pain. The patient had a
      history of normal delivery six months before her admission. In the laparoscopy
      the authors reported finding bilateral Lacerations in the posterior leaf of the
      broad Ligament. Coagulation of both lacerations was performed and the patient
      reported significant improvement in her complaints. The relevant literature was
      reviewed and the article discusses the process of diagnosis and treatment.

PMID- 19848328
TI  - [Fallopian tube torsion--a rare complication in the reproductive age].
AB  - Isolated fallopian tube torsion (ITT) is a rare condition defined as a total or
      partial rotation of the fallopian tube around its vascular axis. The torsion
      initiaLLy interferes with the venous and lymphatic circulation. If unrelieved in
      time, rapid progression occurs, occluding the arterial circulation and Leading to
      gangrene and hemorrhagic necrosis. The cLinicaL appearance usually includes sharp
      lower abdominal pain, with or without peritoneal signs. Urinary and
      gastrointestinal signs might also occur. isolated fallopian tube is a rare
      condition; the incidence s estimated to be 1:500,000 mostly in reproductive age
      women. ITT is most common in the right side, although several reports claim that
      there is no difference between the sides. The etiology is not completely
      understood, but tubal anomalies (anatomic or physiologic) as well as trauma or
      pelvic inflammation are predisposing factors. The clinical appearance and the
      imaging in these cases are not pathognomonic, and many cases are delayed by means
      of diagnosis and treatment. The treatment is surgical. Detorsion or salpingectomy
      is usually performed by laparoscopy. Three cases that were treated lately at the
      Department of Obstetrics and Gynecology at the Hadassah Medical Center are
      presented together with a review of the literature.

PMID- 19848327
TI  - [The treatment of post partum pain: survey of 26 maternity departments in
      Israel].
AB  - BACKGROUND: The majority of post-partum women suffer from pain after vaginal
      delivery, more so after cesarean section. In most cases, pain management is
      needed during the post-partum hospitalization period. In Israel there is no
      national protocol of post-partum pain management. GOALS: Presentation of the
      current status of post-partum pain management used in Israeli hospital maternity
      departments as a basis for a national protocol of postpartum pain management.
      METHODS: During the months of July and August 2008, Israeli maternity departments
      were surveyed by telephone interviews regarding their pain management protocols
      for post-vaginal deliveries and caesarean sections for both breastfeeding and non
      breastfeeding mothers. RESULTS: Treatment protocols were received from 26
      maternity departments. All use paracetamol per-os alone or combined with another
      drug. Dipyrone is used in 22/26 departments, despite the fact that this
      medication is not approved for use during Lactation. In 15/26 departments,
      dictofenac is used mostly after caesarean sections. In nine departments,
      ibuprofen is used post-partum, and tramadol is used in seven. In 20/26
      departments surveyed, opioids are used after cesarean section, mostly morphine or
      pethidine. Methadone is used after caesarean section in two departments.
      CONCLUSIONS: Post-partum pain management treatment in Israelis not standardized,
      especially for Lactating mothers and women after caesarean sections. Lactating
      mothers should be started on paracetamol or ibuprofen per-os, as first-line
      postpartum pain management treatment. If this is not effective, second line
      treatment can be short-term morphine, codeine or propoxyphene. These medications
      are safer than acetylsalicylic acid, dipyrone or pethidine for lactating mothers.

PMID- 19848329
TI  - [A surprise in the bladder: the case of the misplaced gortex].
AB  - A fifty-three-year-old vaginally primipara was evaluated for urinary mixed
      incontinence symptoms and POP-Q stage II pelvic organ prolapse. Her past medical
      history was significant for Burch colposuspension conducted six years prior to
      her referral. Review of the operative report indicated prior use of six peri
      urethral gortex sutures attached to Cooper's ligament. There was no documentation
      of cystoscopy at the end of the procedure. Following the surgery, the patient had
      persistent stress urinary incontinence symptoms and multiple episodes of poorly
      documented urinary tract infections. After evaluation for worsening symptoms of
      mixed urinary incontinence and symptomatic proLapse, the patient underwent a
      suburethral rectus fasciaL sling and sacrocolpopexy for her pelvic organ
      prolapse. FoLlowing an uneventful procedure, cystoscopy to document Lower urinary
      tract safety revealed a urothelial-covered gortex suture and tissue bridge in the
      bladder. The gortex suture was found to be attached to Cooper's ligament,
      consistent with patient's prior history of Burch colposuspension. Via the open
      abdominal incision, the intravesical suture was cut at its connection to Cooper's
      ligament. Through a transvesical approach, the intravesical suture and tissue
      bridge were incised and removed. The postoperative course was uneventful. This
      case report emphasizes the importance of intraoperative cystoscopy following an
      incontinence procedure. This abnormal appearance of the bladder lining is
      consistent with intravesical surgical materials complications. Intravesical
      surgical materials may contribute to persistent urinary symptoms or recurrent
      urinary tract infections (UTIs) in selected women. Detection and removal of these
      materials is recommended.

PMID- 19848330
TI  - [Umbilical cord cyst--should it concern us?].
AB  - INTRODUCTION: Advancements in sonographic technology have led to improved
      prenatal detection of fetal umbilical cord and placental anomalies. The
      prevalence of umbilical cord cystic masses detected in the first trimester is
      0.4% to 3.4%. The second- and third-trimester umbilical cord cysts are a rare
      sonographic finding and its prevalence is unknown. There is a strong association
      between umbilical cord cysts and fetal anomalies but not in all cases. The main
      questions are: what are the implications of these findings and what is the
      prenatal follow-up that should be offered. CASE REPORT: In this study the authors
      present a case in which an umbilical cord cyst was diagnosed at 29 weeks of
      gestation following normal integrated test and anatomical sonographic survey. At
      32 weeks of gestation, fetal karyotype was found to be normal. The outcome of the
      pregnancy was normal and so was the developmental follow-up during the first
      three years. DISCUSSION AND CONCLUSIONS: From the literature survey it appears
      that transient first-trimester cysts are not associated with chromosomal
      anomaLies, yet they might be associated with congenital maLformations, especially
      those of the abdominal wall and the urinary tract, and should lead to further
      detailed sonographic evaluation. Routine karyotype may not be necessary. Second
      and third trimester umbilical cord cystic masses accompanied by additional
      malformations are strongly associated with chromosomal anomalies, especially with
      trisomy 18. Second- and third-trimester umbilical cord cystic masses without
      additional abnormal findings were also found to be associated with chromosomal
      anomalies in some works. Therefore, these findings should be an indication for
      fetal karyotype. In the case of an isolated umbilical cord cyst with normal
      karyotype, serial sonographic evaluation is needed. If all these are normal, it
      may be presumed that the cyst is an isolated umbilical cord anomaly and that the
      fetal prognosis is good.

PMID- 19848331
TI  - [Laparoscopic surgery training system in gynecology].
AB  - With the increasing demand of Laparoscopic surgery, many departments are
      considering the development of surgical skills centers. The authors describe
      their hospitaLs endoscopic training program which includes a theoretical
      curriculum and an inexpensive laparoscopic simulator The system is designed in
      order to improve basic skills of laparoscopic surgery. Other systems available
      elsewhere are discussed.

PMID- 19848332
TI  - [Research and medicine in obstetrics and gynecology].
AB  - The current issue of "Harefuah" is dedicated to original and descriptive research
      as well as to reviews of obstetric and gynecological topics. Original research
      includes the study on the progesterone receptor's profile in endometrial
      carcinoma cell lines, as well as the correlation of maternal serum and amniotic
      fluid Leptin Levels with neonatal birth weight. There are three descriptive
      articles and one review that are related to pain in gynecology and post partum,
      and two articles describing one complication and the second presenting a
      simulation of gynecological surgery. ULtrasound is represented in one descriptive
      case and two reviews describe sonographic signs for chromosomal abnormalities and
      fetal viral infection.

PMID- 19848333
TI  - [Preconception care and counseling for women with diabetes and those at risk for
      diabetes].
AB  - Diabetes is a chronic disease with increasing incidence in recent years in
      parallel with the obesity epidemic. Diabetes can cause damage to many target
      organs and pregnancy in women with pregestational diabetes is considered a high
      risk pregnancy and constitutes a special challenge. Pregestational diabetes
      increases the risk of pregnancy complications to the mother, fetus and newborn
      infant. The duration and type of diabetes, its severity, the occurrence of
      chronic complications and the level of glucose control are the major factors
      influencing pregnancy outcome. Diabetes substantially increases the risk of
      spontaneous abortion and congenital malformations. In order to minimize these
      risks, it is important that all women with pregestational diabetes will receive
      appropriate preconception counseling and treatment.

PMID- 19848334
TI  - [The use of a synthetic analog of prostaglandin E1 for medical treatment of first
      trimester pregnancy failure].
AB  - First trimester failure is a common event accruing in 15-20% of pregnancies that
      has traditionally been treated by surgical curettage. An alternate therapy is
      medical treatment using misoprostol, a synthetic analog of prostaglandin E1.
      Numerous studies have been carried out comparing treatment by misoprostol with a
      placebo. They have found a significant advantage to misoprostol mode of
      treatment. Other studies comparing surgical and medical treatment found the
      surgical treatment to be superior to the latter. It must be noted that the
      medical mode of treatment was indeed found to be successful in over 80% of cases.
      No significant differences were noted in the complication rates of the two
      groups. Misoprostol therapy has been found to be effective when administered
      orally or vaginally, although vaginal therapy is slightly superior. No large
      scale studies have been carried out to date testing the safety of this treatment
      in patients with a scarred uterus (due to Cesarean section or hysterotomy).
      However, on the basis of reported facts, it seems plausibLe to suggest
      misoprostoL treatment for these patients.

PMID- 19848335
TI  - [The genetic sonogram].
AB  - Mid-trimester soft sonographic markers have been linked with aneuploidies. This
      article describes the individual sonographic markers used in the genetic
      sonograms, and reviews the current relevant Literature. The significant soft
      markers are: nuchal thickness, echogenic bowel, shortened limbs and absence of
      nasal bone. The soft markers which are not significant as an isolated finding in
      young patients but are significant in combination with the biochemical markers,
      or in older age are: intracardiac echogenic focus, choroid pLexus cyst,
      pyelectasis and single umbilical artery. There are several other reported
      findings which might be linked to chromosomal abnormalities including hypoplasia
      of the middle phalanx of the fifth digit, sandal gap, ear size, brachycephaly,
      cervical cyst, iliac angle and others. These findings shouLd not be considered as
      soft markers since they were reported only in small series or case reports. The
      aneuploidy risk should be calcuLated on the basis of age, nuchal translucency,
      biochemical screening and anomaly scan. If the calculated risk for aneupLoidy
      exceeds 1:380, an invasive karyotyping procedure should be recommended. Adoption
      of this approach will reduce the unnecessary invasive tests, reduce abortion rate
      and will increase the detection rate of aneuploidy.

PMID- 19848336
TI  - [Ultrasound in the evaluation of intrauterine infection during pregnancy].
AB  - Ultrasound has an important role in the detection and follow- up of intrauterine
      infection. Viral infections are a major cause of fetal morbidity and mortality.
      Transplacental transmission of the virus, even in sub-clinical maternal
      infection, may result in a severe congenital syndrome. Prenatal detection of
      viral infection is based on fetal sonographic findings and PCR to identify the
      specific infectious agent. Most affected fetuses appear sonographically normal,
      but serial scanning may reveal evolving findings. Common sonographic
      abnormalities, although non-specific, may be indicative of fetal viral
      infections. These include growth restriction, ascites, hydrops, ventriculomegaly,
      intracranial calcifications, hydrocephaly, microcephaly, cardiac anomalies,
      hepatosplenomegaly, echogenic bowel, placentomegaly and abnormal amniotic fluid
      volume. Some of the pathognomonic sonographic findings enable diagnosis of a
      specific congenital syndrome (e.g., ventriculomegaly and intracranial and hepatic
      calcifications in cytomegalovirus or in toxoplasma; eye and cardiac anomalies in
      congenital Rubella syndrome; limb contractures and cerebral anomalies in
      Varicella Zoster virus). When abnormalities are detected on ultrasound, a
      thorough fetal evaluation is recommended because of multiorgan involvement.

PMID- 19848337
TI  - [Vestibulodynia--the Israeli experience].
AB  - The cause of vestibulitis, currently known as vestibulodynia, is still an enigma.
      Among those attempting to decipher the puzzle, Israeli researchers are well
      represented. This article reviews the developments in terminology, etiology,
      treatment, and research directions, with an emphasis on the role of IsraeLi
      research. Forty-four articles, covering a range of aspects of vestibulodynia, are
      testimony to the commendable contribution of Israeli research to the
      understanding of this disease. For example, the finding of mast cell
      proLiferation and degranulation, enhanced heparanase expression, and the
      resultant increase and penetration of nerve fibers into the epithelial emanates
      from Israel. Furthermore, an Israeli first proposed the new name, vestibulodynia.
      Implemented in the 1980s, immediately after its initiation in the United States,
      surgical treatment and research in Israel is at the forefront in the world.
      Israeli teams investigating the effectiveness of surgical treatment conclude that
      perineoplasty is more successful than any other treatment. Nonetheless, with 57%
      complete response, and 89% improvement, surgery does not cure all those suffering
      from vestibulodynia.

PMID- 19848338
TI  - [Mental illness common among physicians. To seek help for stress and mental
      problems is not always easy].

PMID- 19848339
TI  - [Exercise-induced asthma could be laryngeal obstruction. Not uncommon among young
      sportsmen--avoiding the wrong treatment is important].

PMID- 19848340
TI  - [Variation of internship test results depends on the seat of learning and age.
      Analysis of tests 1995-2008].

PMID- 19848341
TI  - [Good immune response of diphtheria-tetanus-pertussis vaccination in the 4th
      grade. Local reaction very common--and expected].

PMID- 19848343
TI  - [A tool for more constructive feedback in clinical guidance. Feedback tool tested
      using students and supervisors in a pilot study].

PMID- 19848342
TI  - [High-technology revolutionizes craniofacial surgery. Computer navigation for
      better precision and fewer complications].

PMID- 19848344
TI  - [Heart surgery in Sudan. Experiences from a highly specialized cardiac surgical
      centre managed by an Italian humanitarian organization].

PMID- 19848346
TI  - [Health data registries necessary for follow-up of the quality of health care!].

PMID- 19848345
TI  - [Hepatic adverse effects of allopurinol].

PMID- 19848347
TI  - [Treatment of vocal cord dysfunction: information and respiratory therapy, not
      surgery].

PMID- 19848349
TI  - [Drug committees' information leaflets are needed].

PMID- 19848348
TI  - [To be or not to be for cefuroxime].

PMID- 19848350
TI  - ["Death sleeps in life and life sleeps in death". The enigma of suicide--the
      example Stig Dagerman].

PMID- 19848351
TI  - A continued commitment to excellence.

PMID- 19848352
TI  - Cardiovascular disease and sleep disordered breathing: are children vulnerable?

PMID- 19848353
TI  - Slow waves and learning: beyond correlations.

PMID- 19848354
TI  - The chicken-or-egg debate in OSA pathogenesis.

PMID- 19848355
TI  - Endothelial function in normotensive men with obstructive sleep apnea before and
      6 months after CPAP treatment.
AB  - STUDY OBJECTIVES: To evaluate endothelium-dependent flow-mediated dilation (FMD)
      and endothelium-independent nitroglycerin (NTG)-induced dilation of the brachial
      artery with Doppler ultrasound in patients with obstructive sleep apnea (OSA) and
      impact of six months of continuous positive airway pressure (CPAP) treatment.
      DESIGN: A prospective, controlled, observational study. SETTING: Single-site,
      clinic-based. PATIENTS: Twenty-nine normotensive men with OSA (apnea-hypopnea
      index [AHI], mean +/- SD, 60.4 +/- 22.1-h), and 17 men without OSA (AHI 2.5 +/-
      0.6-h). INTERVENTIONS: Six months of CPAP therapy in OSA patients. MEASUREMENTS
      AND RESULTS: FMD was lower in patients with OSA compared with in controls (7.19
      +/- 1.78% vs 10.93 +/- 2.59%; P < 0.001) while NTG-induced vasodilation was
      similar in both groups (13.75 +/- 1.01% vs 14.25 +/- 1.83%; n.s.). An inverse
      relationship was found between FMD and AHI adjusted for age and body mass index
      (BMI) (beta = - 0.05, P < 0.001). Following 6 months of CPAP treatment in the OSA
      group, FMD was increased from 7.38 +/- 2.06% to 10.45 +/- 1.68; P = 0.001) in 20
      patients compliant with the device whereas the corresponding values did not
      change in the non-user group (7.08 +/- 1.50% vs 7.26 +/- 1.01%). No significant
      changes were observed regarding the NTG-induced vasodilation after CPAP compared
      with the baseline values. CONCLUSIONS: Our results confirm the previous reports
      suggesting impaired endothelium-dependent FMD in OSA, and additionally document
      the sustained improvement in endothelial function after 6 months of CPAP
      treatment in complaint patients.

PMID- 19848356
TI  - Acute cardiovascular changes with obstructive events in children with sleep
      disordered breathing.
AB  - STUDY OBJECTIVES: Obstructive apneas in adults are associated with acute changes
      in blood pressure (BP) and heart rate (HR) that may contribute to poor
      cardiovascular outcome. Children with sleep disordered breathing (SDB) are
      similarly at risk for cardiovascular complications. We aimed to test the
      hypothesis that BP and HR are augmented during obstructive events in children
      equivalent to levels reported in adults. DESIGN: Beat-by-beat mean arterial
      pressure (MAP) and HR were analyzed over the course of obstructive events (pre,
      early, late, and post-event) during NREM and REM sleep and compared using 2-way
      ANOVA with post hoc analyses. SETTING: Pediatric sleep laboratory. PATIENTS OR
      PARTICIPANTS: 30 children (15M/15F) aged 7-12 y referred for investigation of SDB
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All children underwent overnight
      polysomnography with continuous BP recording. MAP and HR increased significantly
      from late to post event in both sleep states (mean +/- SEM, NREM: MAP, 74 +/- 3
      to 93 +/- 3 mm Hg; HR, 76 +/- 2 to 97 +/- 2 bpm. REM: MAP, 76 +/- 3 to 89 +/- 3
      mm Hg; HR, 76 +/- 2 to 91 +/- 2 bpm. P < 0.05 for all). NREM sleep state and
      arousal from sleep were significant independent predictors of the magnitude of
      cardiovascular change from late to post event (P < 0.05 for all). CONCLUSIONS:
      Children with SDB experience significant changes in HR and BP during obstructive
      events with magnitudes that are similar to levels reported in adults. These
      changes are more pronounced during NREM sleep and with arousal. These acute
      cardiovascular changes may have important implications for poor cardiovascular
      outcome in children with OSA as repetitive cardiovascular perturbations may
      contribute to the development of hypertension.

PMID- 19848357
TI  - Sleep-dependent improvement in visuomotor learning: a causal role for slow waves.
AB  - STUDY OBJECTIVES: Sleep after learning often benefits memory consolidation, but
      the underlying mechanisms remain unclear. In previous studies, we found that
      learning a visuomotor task is followed by an increase in sleep slow wave activity
      (SWA, the electroencephalographic [EEG] power density between 0.5 and 4.5 Hz
      during non-rapid eye movement sleep) over the right parietal cortex. The SWA
      increase correlates with the postsleep improvement in visuomotor performance,
      suggesting that SWA may be causally responsible for the consolidation of
      visuomotor learning. Here, we tested this hypothesis by studying the effects of
      slow wave deprivation (SWD). DESIGN: After learning the task, subjects went to
      sleep, and acoustic stimuli were timed either to suppress slow waves (SWD) or to
      interfere as little as possible with spontaneous slow waves (control acoustic
      stimulation, CAS). SETTING: Sound-attenuated research room. PARTICIPANTS: Healthy
      subjects (mean age 24.6 +/- 1.0 years; n = 9 for EEG analysis, n = 12 for
      behavior analysis; 3 women). MEASUREMENTS AND RESULTS: Sleep time and efficiency
      were not affected, whereas SWA and the number of slow waves decreased in SWD
      relative to CAS. Relative to the night before, visuomotor performance
      significantly improved in the CAS condition (+5.93% +/- 0.88%) but not in the SWD
      condition (-0.77% +/- 1.16%), and the direct CAS vs SWD comparison showed a
      significant difference (P = 0.0007, n = 12, paired t test). Changes in visuomotor
      performance after SWD were correlated with SWA changes over right parietal cortex
      but not with the number of arousals identified using clinically established
      criteria, nor with any sign of "EEG lightening" identified using a novel
      automatic method based on event-related spectral perturbation analysis.
      CONCLUSION: These results support a causal role for sleep slow waves in sleep
      dependent improvement of visuomotor performance.

PMID- 19848358
TI  - An ERP examination of the different effects of sleep deprivation on exogenously
      cued and endogenously cued attention.
AB  - BACKGROUND: Behavior and neuroimaging studies have shown selective attention to
      be negatively impacted by sleep deprivation. Two unresolved questions are (1)
      whether sleep deprivation impairs attention modulation of early visual processing
      or of a later stage of cognition and (2) how sleep deprivation affects
      exogenously versus endogenously driven selective attention. STUDY OBJECTIVES: To
      investigate the time course and different effects of sleep deprivation on
      exogenously and endogenously cued selective attention. DESIGN: Participants
      performed modified Attention Network Tests (ANTs) using exogenously and
      endogenously cued targets to index brain networks underlying selective attention.
      Target-locked event-related potentials (ERPs) were recorded as participants
      performed the Attention Network Tests on 2 days separated by 24 hours of total
      sleeplessness. PARTICIPANTS: Fourteen US Military Academy cadets and 12 US Army
      soldiers from the Ironhorse Brigade, Ft. Hood, Texas. MEASUREMENT AND RESULTS:
      For both Attention Network Tests, sleep deprivation led to slowed response times,
      decreased accuracy rates, a diminished positive P3 (450- to 550-ms) ERP
      component, and an enhanced P2 (312- to 434-ms) ERP component. In contrast, the
      parietal N1 (157- to 227-ms) ERP response was reduced with sleep deprivation for
      endogenously, but not exogenously, cued targets. These sleep deprivation-related
      effects occurred in the context of typical behavior and ERP patterns expected in
      a cued spatial-attention task. CONCLUSIONS: These findings suggest that as little
      as 24 hours of sleep deprivation affects both early and late stages of attention
      selection but affects endogenously driven selective attention to a greater degree
      than it does exogenously driven selective attention.

PMID- 19848359
TI  - Sleep deprivation in pigeons and rats using motion detection.
AB  - STUDY OBJECTIVES: Forced sleep deprivation results in substantial behavioral and
      physiologic effects in mammals. The disk-over-water (DOW) method produces a
      syndrome characterized by increased energy expenditure and a robust
      preferentially rapid-eye-movement sleep rebound upon recovery or eventual death
      after several weeks of sleep deprivation. The DOW has been used successfully only
      in rats. This paper presents a method to enforce long-term controlled sleep
      deprivation across species and to compare its effects in rats and pigeons. DESIGN
      AND INTERVENTION: A conveyor was substituted for the DOW disk. Behavior rather
      than electroencephalography was used to trigger arousal stimuli, as in gentle
      handling deprivation. Rats and pigeons were deprived using this apparatus, and
      the results were compared with each other and with published reports.
      MEASUREMENTS AND RESULTS: The physiologic consequences and recovery sleep in rats
      were like those published for DOW rats. Magnitude of sleep loss and recovery
      patterns in pigeons were similar to those seen in rats, but expected symptoms of
      the sleep deprivation syndrome were absent in pigeons. The use of a motion
      trigger allowed us to measure and, thus, to assess the quality and impact of the
      procedure. CONCLUSION: Prolonged and controlled sleep deprivation can be enforced
      using automated motion detection and a conveyor-over-water system. Pigeons and
      rats, deprived of sleep to the same extent, showed similar patterns of recovery
      sleep, but pigeons did not exhibit the hyperphagia, weight loss, and debilitation
      seen in rats.

PMID- 19848361
TI  - Sleep stage dynamics differ between children with and without obstructive sleep
      apnea.
AB  - STUDY OBJECTIVES: Analysis of sleep dynamics--distributions of contiguous sleep
      and sleep stage durations--reveal exponential distributions and potential
      clinical utility in adults. We sought to examine these polysomnographic variables
      for the first time in children, and in the context of childhood sleep disordered
      breathing (SDB). DESIGN AND SETTING: Analysis of polysomnographic data available
      from the Washtenaw County Adenotonsillectomy Cohort. PARTICIPANTS: Selected
      subjects were 48 children aged 5-12 years with SDB (pediatric apnea/hypopnea
      index > or = 1.5) who were scheduled for adenotonsillectomy and 20 control
      subjects of similar ages without SDB. Subjects were studied at enrollment and
      again one year later in almost all cases. RESULTS: Durations of sleep and
      specific sleep stage bouts generally followed exponential distributions. At
      baseline, the number of sleep stage changes, proportion of total sleep time
      occupied by stage 1 sleep, proportion stage 2 sleep, mean stage 2 duration, and
      mean stage REM duration each distinguished subjects with and without SDB (P <
      0.05), but only mean stage 2 duration did so independently after accounting for
      the other variables (P = 0.03). At one-year follow-up, changes in total sleep
      time, mean stage 2 duration, and mean stage REM duration distinguished SDB from
      control subjects, but again only changes in mean stage 2 duration did so
      independently (P = 0.01). CONCLUSIONS: Durations of uninterrupted sleep and
      specific sleep stages appear to follow exponential distributions in children with
      or without SDB. Parameters that describe these distributions--particularly mean
      duration of stage 2 sleep periods--may provide useful additions to standard sleep
      stage analyses.

PMID- 19848360
TI  - Modulation of genioglossus muscle activity across sleep-wake states by histamine
      at the hypoglossal motor pool.
AB  - STUDY OBJECTIVES: Histamine neurons comprise a major component of the aminergic
      arousal system and significantly influence sleep-wake states, with antihistamines
      widely used as sedative hypnotics. Unlike the serotonergic and noradrenergic
      components of this arousal system, however, the role of histamine in the central
      control of respiratory motor activity has not been determined. The aims of this
      study were to characterize the effects of histamine receptor agonists and
      antagonists at the hypoglossal motor pool on genioglossus muscle activity across
      sleep and awake states, and also determine if histamine contributes an endogenous
      excitatory drive to modulate hypoglossal motor outflow to genioglossus muscle.
      DESIGN, PARTICIPANTS, AND INTERVENTIONS: Thirty-three rats were implanted with
      electroencephalogram and neck electrodes to record sleep-wake states, and
      genioglossus and diaphragm electrodes for respiratory muscle recordings.
      Microdialysis probes were inserted into the hypoglossal motor nucleus.
      MEASUREMENTS AND RESULTS: Histamine at the hypoglossal motor nucleus
      significantly increased tonic genioglossus muscle activity in wakefulness, non
      REM sleep and REM sleep. The activating effects of histamine on genioglossus
      muscle activity also occurred with a histamine type-1 (H1) but not H2 receptor
      agonist. However, H1 receptor antagonism at the hypoglossal motor nucleus did not
      decrease genioglossus muscle activity in wakefulness or sleep. CONCLUSIONS: The
      results suggest that histamine at the hypoglossal motor pool increases
      genioglossus muscle activity in freely behaving rats in wakefulness, non-REM, and
      REM sleep via an H1 receptor mechanism.

PMID- 19848362
TI  - Sleep spindle activity is correlated with reading abilities in developmental
      dyslexia.
AB  - STUDY OBJECTIVES: To analyze sleep architecture of children with dyslexia, by
      means of conventional parameters and EEG spectral analysis and to correlate sleep
      parameters and EEG spectra with neuropsychological measures. DESIGN: Cross
      sectional study involving validated sleep questionnaires, neuropsychological
      scales, and polysomnographic recordings. SETTING: Sleep laboratory in academic
      center. PARTICIPANTS: Sixteen subjects with developmental dyslexia (mean age 10.8
      years) and 11 normally reading children (mean age 10.1 years). All the subjects
      underwent overnight polysomnographic recording; EEG power spectra were computed
      from the Cz derivation and spindle density was calculated during sleep stages N2.
      INTERVENTION: N/A. MEASUREMENTS AND RESULTS: Dyslexic children showed an increase
      in power of frequency bands between 0.5-3 Hz and 11-12 Hz in stage N2 and between
      0.5-1 Hz in stage N3; they also showed significantly increased spindle density
      during N2. The power of the sigma band in N2 was positively correlated with the
      Word reading and MT reading tests; similarly, spindle density was significantly
      correlated with the Word reading test. The increased spindle activity and EEG
      sigma power in dyslexic subjects were found to be correlated with the degree of
      dyslexic impairment. CONCLUSIONS: The correlation found between sleep spindle
      activity and reading abilities in developmental dyslexia supports the hypothesis
      of a role for NREM sleep and spindles in sleep-related neurocognitive processing.

PMID- 19848363
TI  - Impact of alcoholism on sleep architecture and EEG power spectra in men and
      women.
AB  - STUDY OBJECTIVES: To determine the impact of alcoholism on sleep architecture and
      sleep EEG power spectra in men and women with uncomplicated alcoholism. DESIGN
      AND PARTICIPANTS: 42 alcoholics (27 men) and 42 controls (19 men) screened for
      medical, psychiatric, and sleep problems participated in a full night of
      polysomnography following an adaptation night. Data were collected from multiple
      scalp sites and subjected to power spectral analysis. Sleep architecture and EEG
      spectral power measures were evaluated for the effects of diagnosis and sex using
      age as a covariate. RESULTS: Compared with controls, alcoholics had less slow
      wave sleep and increased proportions of stage 1 and REM sleep. Spectral analysis
      of NREM sleep showed reduced levels of slow wave activity (SWA, 0.3-4 Hz) and
      slow theta (theta) power (4-6 Hz) in alcoholics. The differences in SWA extended
      across the slow band (0.3-1 Hz) and all delta (delta) frequencies and were most
      prominent over frontal scalp regions. No group differences were seen in the power
      spectra of REM sleep. Women had more SWA and theta power than men, but there were
      no sex by diagnosis interactions for any measures, suggesting that alcoholism
      does not differentially influence men and women. CONCLUSION: Long-term alcoholism
      affects sleep even after long periods of abstinence in both men and women.
      Measures of frontal slow wave activity were particularly sensitive markers of
      this long-lasting effect. Sleep EEG measures would thus seem to provide a
      functional correlate of the changes in brain structure seen in frontal cortex of
      long-term alcoholics.

PMID- 19848364
TI  - Determinants of ventilatory instability in obstructive sleep apnea: inherent or
      acquired?
AB  - STUDY OBJECTIVES: Certain respiratory control characteristics determine whether
      patients with collapsible upper airway develop stable or unstable breathing
      during sleep, thereby influencing the severity of obstructive apnea (OSA). These
      include arousal threshold (T(A)), response to transient hypoxia and hypercapnia
      (Dynamic Response) and the increase in respiratory drive required for arousal
      free airway opening (T(ER)). We wished to determine whether these characteristics
      are inherent or are acquired during untreated OSA. DESIGN: T(A), Dynamic
      Response, and T(ER) were measured in patients with severe OSA before and after
      treatment with continuous positive airway pressure (CPAP). Changes observed after
      treatment were deemed to have been acquired during untreated OSA. SETTING:
      University-based sleep laboratory. PATIENTS: 15 patients with severe OSA.
      INTERVENTIONS: (1) 30-sec alterations in inspired gases during sleep on CPAP. (2)
      Brief dial-downs of CPAP (dial-downs) both during air breathing and when
      ventilation was increased to different levels. MEASUREMENTS AND RESULTS: T(A):
      the increase in ventilation associated with a 50% probability of arousal
      (T(A)50). Dynamic Response: the increase in ventilation on the 5th breath
      following breathing 3% CO2 in 11% to 15% O2. T(ER): the increase in ventilation
      prior to dial-downs that was associated with an arousal-free airway opening
      during dial-down. CPAP therapy (10.5 +/- 4.3 months) resulted in marked reduction
      in Dynamic Response (131% +/- 95% to 52% +/- 34% baseline ventilation, P <
      0.005), a decrease in T(A)50 (134% +/- 78% to 86% +/- 47% baseline ventilation, P
      < 0.05), and no change in T(ER). CONCLUSIONS: T(ER) may be an inherent
      characteristic. Untreated OSA results in an increase in dynamic response to
      asphyxia and an increase in arousal threshold.

PMID- 19848366
TI  - An improved methodology for individualized performance prediction of sleep
      deprived individuals with the two-process model.
AB  - We present a method based on the two-process model of sleep regulation for
      developing individualized biomathematical models that predict performance
      impairment for individuals subjected to total sleep loss. This new method
      advances our previous work in two important ways. First, it enables model
      customization to start as soon as the first performance measurement from an
      individual becomes available. This was achieved by optimally combining the
      performance information obtained from the individual's performance measurements
      with a priori performance information using a Bayesian framework, while retaining
      the strategy of transforming the nonlinear optimization problem of finding the
      optimal estimates of the two-process model parameters into a series of linear
      optimization problems. Second, by taking advantage of the linear representation
      of the two-process model, this new method enables the analytical computation of
      statistically based measures of reliability for the model predictions in the form
      of prediction intervals. Two distinct data sets were used to evaluate the
      proposed method. Results using simulated data with superimposed white Gaussian
      noise showed that the new method yielded 50% to 90% improvement in parameter
      estimate accuracy over the previous method. Moreover, the accuracy of the
      analytically computed prediction intervals was validated through Monte Carlo
      simulations. Results for subjects representing three sleep-loss phenotypes who
      participated in a laboratory study (82 h of total sleep loss) indicated that the
      proposed method yielded individualized predictions that were up to 43% more
      accurate than group-average prediction models and, on average, 10% more accurate
      than individualized predictions based on our previous method.

PMID- 19848365
TI  - Sex differences in subjective and actigraphic sleep measures: a population-based
      study of elderly persons.
AB  - STUDY OBJECTIVES: To investigate and explain sex differences in subjective and
      actigraphic sleep parameters in community-dwelling elderly persons. DESIGN: Cross
      sectional study. SETTING: The study was embedded in the Rotterdam Study, a
      population-based study. PARTICIPANTS: Nine hundred fifty-six participants aged 59
      to 97 years. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Participants wore an
      actigraph and kept a sleep diary for an average of 6 consecutive nights.
      Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index.
      Unadjusted sex differences in sleep parameters were assessed with t tests. Women
      reported shorter total sleep time, a less favorable sleep-onset latency, lower
      sleep efficiency, and worse global sleep quality, as compared with men. When
      assessed with actigraphy, however, women were found to have longer and less
      fragmented sleep than men. Sex differences in diary-reported sleep duration and
      other subjective sleep parameters were attenuated by adjustment for marital
      status, the use of sleep medication, and other covariates, but all sex
      differences remained significant in a multivariate-adjusted model. Sex
      differences in actigraphic sleep parameters were barely attenuated by
      multivariate adjustment, although the shorter actigraphically measured sleep
      duration in men was partly explained by their higher alcohol consumption. Some
      covariates (eg, sleep medication) had a different relationship with diary
      reported or actigraphic total sleep time in men and women. CONCLUSIONS: If
      assessed by diary or interview, elderly women consistently reported shorter and
      poorer sleep than elderly men. In contrast, actigraphic sleep measures showed
      poorer sleep in men. These discrepancies are partly explained by determinants of
      sleep duration, such as sleep medication use and alcohol consumption.

PMID- 19848368
TI  - Bahrain 2009: NIDEK presentations during the 10th Middle East African Council of
      Ophthalmology International Congress.

PMID- 19848367
TI  - The variable response-stimulus interval effect and sleep deprivation: an
      unexplored aspect of psychomotor vigilance task performance.
AB  - STUDY OBJECTIVES: The Psychomotor Vigilance Task (PVT) contains variable response
      stimulus intervals (RSI). Our goal is to investigate the effect of RSI on
      performance to determine whether sleep deprivation affects the ability to attend
      to events across seconds and whether this effect is independent of impairment in
      sustaining attention across minutes, as measured by time on task. DESIGN: A
      control group following their normal sleep routines and 3 groups exposed to 54
      hours of total sleep deprivation performed a 10-minute PVT every 6 hours for 9
      total test runs. SETTING: Sleep deprivation occurred in a sleep laboratory with
      continuous behavioral monitoring; the control group took the PVT at home.
      SUBJECTS: Eighty-four healthy sleepers (68 sleep deprivation, 16 controls; 22
      women; aged 18-35 years). MEASUREMENTS AND RESULTS: Across groups, as the RSI
      increased from 2 to 10 seconds, mean RT was reduced by 69 milliseconds (main
      effect of RSI, P < 0.001). There was no interaction between the sleep deprivation
      and RSI effects. As expected, there was a significant interaction of sleep
      deprivation and time on task for mean RT (P = 0.002). Time on task and RSI
      effects were independent. Parallel analyses of percentage of lapses and
      percentage of false starts produced similar results. CONCLUSIONS: We demonstrate
      that the cognitive mechanism of attention responsible for response preparation
      across seconds is distinct from that for maintaining attention to task
      performance across minutes. Of these, only vigilance across minutes is degraded
      by sleep deprivation. Theories of sleep deprivation should consider how this
      pattern of spared and impaired aspects of attention may affect real-world
      performance.

PMID- 19848369
TI  - Hideo Ozawa: a personal perspective.

PMID- 19848370
TI  - Customized aspheric treatment zone ablation to treat irregular corneas after
      corneal refractive surgery.
AB  - PURPOSE: To describe the retreatment of highly aberrated corneas due to previous
      keratorefractive surgery using topography-guided aspheric treatments. METHODS:
      Eight eyes (five patients) with reduced mesopic visual quality due to previous
      keratomileusis, excimer laser surgery, or radial keratotomy underwent retreatment
      with the customized aspheric treatment zone (CATz) algorithm with the CXIII
      excimer laser (NIDEK Co Ltd) to correct corneal wavefront aberrations. Before
      CATz treatments, all patients were satisfied with their preoperative photopic
      vision (all 20/30 or better uncorrected) yet were dissatisfied with their vision
      at night. All eyes had >20 microm (range: 20 to 33 microm) of corneal
      irregularity before CATz retreatment. All eyes had a flap cut or flap lift
      procedure for CATz retreatment. RESULTS: One year after treatment with CATz, no
      eyes lost best spectacle-corrected visual acuity (BSCVA); all eyes had BSCVA of
      20/30 or better. Mean modulation transfer function increased by 13% by the end of
      the first postoperative year. A 0.45-microm decrease was noted in coma 1 year
      postoperatively. CONCLUSIONS: The CATz algorithm is effective in the treatment of
      severe corneal irregularities due to previous corneal surgery.

PMID- 19848371
TI  - Comparison of postoperative wavefront aberrations after NIDEK CXIII optimized
      aspheric transition zone treatment and OPD-guided custom aspheric treatment.
AB  - PURPOSE: To compare higher order aberrations of aspheric or wavefront-guided
      myopic LASIK. METHODS: This was a prospective, randomized study of a myopic LASIK
      cohort that was subdivided into two groups; 12 eyes were treated with the
      optimized aspheric transition zone algorithm (OATz group) and 11 eyes were
      treated with wavefront-guided optimized path difference custom aspheric treatment
      (OPDCAT group). Corneal asphericity and higher order aberrations root-mean-square
      were compared between groups before, 1 month, and 3 months after LASIK. Student t
      test was used to assess differences between groups. P<.05 was considered
      statistically significant. RESULTS: At 3 months postoperatively, all eyes in both
      groups had spherical equivalent refraction of +/-0.50 diopters (D). Mean higher
      order aberration increased by 0.18 microm postoperatively in the OATz group
      (P<.05) and decreased by 0.04 microm in the OPDCAT group (P=.819). A
      statistically significant increase in spherical aberration was noted in the OATz
      group only (P<.05). Asphericity showed a statistically significant difference
      between the two groups postoperatively (P<.05). There was a greated tendency for
      increased higher order aberrations in eyes with <0.30 microm of higher order
      aberrations preoperatively in the OPDCAT group. The reverse tendency was observed
      in the OATz group. CONCLUSIONS: OPDCAT induced minimal changes in spherical
      aberration due to lower changes in corneal asphericity compared to the OATz
      group. Eyes with <0.30 microm of higher order aberrations preoperatively are
      likely better candidates for the OATz algorithm than OPDCAT.

PMID- 19848372
TI  - LASIK with the optimized aspheric transition zone and cross-cylinder technique
      for the treatment of astigmatism from 1.00 to 4.25 diopters.
AB  - PURPOSE: The predictability and safety of LASIK with the optimized aspheric
      transition zone (OATz) and cross-cylinder technique were evaluated for the
      surgical correction of myopia with 1.00 to 4.25 diopters (D) of astigmatism.
      METHODS: In this prospective study, 74 eyes of 48 consecutive LASIK patients with
      astigmatism ranging from 1.00 to 4.25 D were evaluated. All eyes underwent laser
      ablation with profile 7 of the OATz algorithm with the NIDEK CXIII excimer laser
      platform. Refractive outcomes, visual acuity, and patient satisfaction were
      assessed based on 6-month postoperative data. RESULTS: Preoperative manifest
      refraction spherical equivalent (MRSE) was -2.10+/-1.19 D (range: -0.50 to -5.75
      D) and mean cylinder was -1.94+/-0.89 D (range: -1.00 to -4.25 D). At 6 months
      postoperatively, the mean MRSE for all eyes was 0.01+/-0.37 D (range: -0.75 to
      +1.00 D). Postoperatively, 78.3% (58/74) of eyes achieved uncorrected visual
      acuity (UCVA) of 20/20 or better, and 97.3% (72/74) of eyes achieved UCVA of
      20/40 or better. Regarding predictability, 94.6% (70/74) of eyes were within +/
      0.50 D of intended MRSE and 98.6% (73/74) of eyes were within +/-1.00 D of
      intended MRSE. Four (5.3%) eyes lost two lines of best spectacle-corrected visual
      acuity at 6 months. Stability was reached between 1 and 3 months and verified at
      6 months postoperatively. CONCLUSIONS: LASIK with OATz and the cross-cylinder
      technique is safe and predictable for the treatment of patients with astigmatism
      up to 4.25 D.

PMID- 19848373
TI  - One-kilohertz eye tracker and active intraoperative torsion detection in the
      NIDEK CXIII and Quest excimer lasers.
AB  - PURPOSE: To describe recent technological additions to the NIDEK CXIII and Quest
      excimer lasers. METHODS: A summary article with data from previous published
      studies outlining the benefits of newer technology. RESULTS: The addition of a 1
      kHz infrared eye tracker decreased the spread of laser spot placement from a mean
      of 228.79 microm without a tracker to 38.47 microm with the eye tracker. The
      addition of real-time torsion error correction produced a statistically
      significantly lower cylinder dispersion, mean manifest refractive cylinder, and
      error of angle postoperatively in eyes that underwent LASIK. CONCLUSIONS: The
      incorporation of an ultrahigh speed eye tracker and active cyclotorsion
      correction surpasses the minimal technology criteria required for accurate
      wavefront-based ablations.

PMID- 19848374
TI  - Visual and optical performance before and after rotation of a misaligned STAAR
      Toric Implantable Collamer Lens.
AB  - PURPOSE: To document the use of the NIDEK OPD-Scan II/Station as a monitoring
      tool and clinical aid in the evaluation and re-rotation of a misaligned STAAR
      Toric Implantable Collamer Lens (TICL). METHODS: A 22-year-old man underwent
      bilateral TICL implantation. Emmetropia was achieved in the left eye after TICL
      implantation; however, the right eye showed residual compound myopic astigmatism.
      Both eyes were evaluated using the OPD-Scan II/Station, and re-rotation of the
      TICL in the right eye was planned using the internal wavefront and corneal
      topography maps. The remaining residual error after re-rotation was treated using
      photorefractive keratectomy (PRK). RESULTS: The left eye showed excellent axis
      alignment and optical quality. The right eye showed a difference of 8 degrees to
      10 degrees in axis of orientation and an under-calculation of the lens power,
      which resulted in poor optical quality. After rotation of the lens and PRK,
      emmetropia was achieved and the patient reported resolution of symptoms. Higher
      order aberrations were reduced by 0.535 microm and the modulation transfer
      function increased 42% compared to initial TICL implantation. CONCLUSIONS:
      Internal and corneal surface aberrometry allowed proper evaluation and precise
      realignment of a TICL. The objective assessment of the internal astigmatism,
      optical quality, and visual performance aids in planning complicated surgical
      cases that require combination surgery to restore visual quality.

PMID- 19848375
TI  - Axis alignment and rotational stability after implantation of the toric
      implantable collamer lens for myopic astigmatism.
AB  - PURPOSE: To assess axis alignment and stability of the Toric Implantable Collamer
      Lens (TICL; STAAR Surgical Co) over time. METHODS: Thirty-five consecutive eyes
      of 19 patients received the TICL for treatment of myopic astigmatism. Manifest
      refraction spherical equivalent (MRSE) and manifest refractive cylinder were
      measured preoperatively and at 3 months postoperatively. The axis alignment of
      the TICL was measured using the internal OPD map obtained with the OPD-Scan II
      (NIDEK Co Ltd). RESULTS: Mean refractive cylinder was reduced from 2.80+/-1.45
      diopters (D) preoperatively to 0.63+/-0.75 D at 3 months postoperatively; MRSE
      was -7.61+/-4.02 D preoperatively and -0.14+/-0.38 D at 3 months. Mean absolute
      value of the measured axis misalignment from baseline (day 1) to 1 month was
      2.90+/-2.11 degrees and from 1 month to 3 months was 4.6+/-11.2 degrees. Mean
      absolute value of the measured changes in axis misalignment from baseline to 3
      months was 2.68+/-2.11 degrees (after excluding one eye that required
      repositioning due to TICL rotation). At 3 months postoperatively, 96.8% (30/31)
      eyes had <or=8 degrees and 90.3% (28/31) had <or=5 degrees of axis misalignment.
      CONCLUSIONS: The TICL showed minimal axis misalignment after implantation and
      remained stable 3 months postoperatively.

PMID- 19848376
TI  - Comparison of myopic LASIK centered on the coaxially sighted corneal light reflex
      or line of sight.
AB  - PURPOSE: To compare refractive outcomes of myopic LASIK with centration on the
      coaxially sighted corneal light reflex (CSCLR) to centration on the center of the
      pupil (line of sight [LOS]). METHODS: The NIDEK CXIII excimer laser was used to
      treat 268 eyes with centration on the CSCLR (CSCLR group) and 288 eyes with
      centration on the LOS (LOS group). For the CSCLR group, the laser ablation was
      delivered 80% closer to the visual axis. One-month postoperative outcomes were
      compared. RESULTS: Preoperative manifest refraction spherical equivalent (MRSE)
      was -4.88+/-1.55 diopters (D) (range: -8.50 to -1.25 D) in the CSCLR group and 
      5.05+/-1.63 D (range: -9.75 to -1.50 D) in the LOS group. The postoperative MRSE
      was 0.17+/-0.39 D (range: -1.38 to -1.25 D) in the CSCLR group and 0.19+/-0.48 D
      (range: -1.63 to +1.88 D) in the LOS group. Safety (1.18) and efficacy (1.047)
      indices were statistically significantly higher in the CSCLR group compared to
      the LOS group (1.138 and 0.997, respectively) (P<.05). This trend was accentuated
      in a subgroup analysis of patients with >0.25-mm difference between the CSCLR and
      LOS, favoring the CSCLR group. A statistically significantly greater induction of
      higher order aberrations (P=.04) and coma (P<.01) was noted in the LOS group
      postoperatively. CONCLUSIONS: Myopic LASIK centered on the CSCLR was
      significantly safer and more effective than LASIK centered on the pupil (LOS),
      with significantly lower induction of coma and total higher order aberrations.

PMID- 19848377
TI  - Total, corneal, and internal ocular optical aberrations in patients with
      keratoconus.
AB  - PURPOSE: To measure and compare total, corneal, and internal ocular aberrations
      using combined wavefront analysis and corneal topography in eyes with keratoconus
      and eyes with normal corneas. METHODS: This prospective study comprised eyes of
      patients with keratoconus and myopic patients seeking refractive surgery.
      Patients diagnosed with keratoconus and with a classification of "normal" or
      "keratoconus" on the NIDEK Corneal Navigator corneal disease screening software
      were selected for inclusion in this study. The normal group comprised eyes with a
      "normal" classification with 99% similarity. In the normal group, only one eye
      per patient was randomly selected based on a randomization schedule. Corneal,
      internal, and total wavefront measurements were provided by the NIDEK OPD-Scan
      II. RESULTS: One hundred eyes with keratoconus and 155 normal eyes were enrolled
      in the study. Statistically significant higher corneal and internal higher order
      aberrations were observed in the eyes with keratoconus (P<.05). However, an
      increase in ocular higher order aberrations proportional to corneal higher order
      aberrations was not observed in the keratoconus group. CONCLUSIONS: A
      compensatory effect of increased anterior corneal aberrations by internal
      aberrations in keratoconic eyes was present for some aberrations. The origin of
      this compensation and the optical mechanism behind it requires further study.

PMID- 19848378
TI  - Keratoconus detection using corneal topography.
AB  - PURPOSETo review the topographic patterns associated with keratoconus suspects
      and provide criteria for keratoconus screening. METHODS: Case study using maps
      from the NIDEK OPD-Scan II and OPD Station to highlight patterns seen in
      keratoconic corneas. RESULTS: Five criteria are listed for the detection of
      keratoconus: 1) apex of the cone is not centered at the 6-o'clock semi-meridian,
      2) cone should appear round on the tangential map, 3) keratometry >45.00
      diopters, 4) corneal thickness at the apex of the cone is approximately 30 microm
      thinner than the corresponding distance above the pupil center, and 5)
      topographic patterns are not symmetric. CONCLUSIONS: Standard corneal topography
      maps and simple clinical evaluation criteria are fundamental to detect
      keratoconus suspects and keratoconus.

PMID- 19848380
TI  - Advances in organic photoconductor technology.

PMID- 19848379
TI  - Confocal microscopy of corneal stroma and endothelium after LASIK and PRK.
AB  - PURPOSE: To compare with confocal microscopy the changes in stromal keratocyte
      density and endothelial cell count due to photorefractive keratectomy (PRK) and
      LASIK. METHODS: In this prospective study, 32 eyes (16 myopic patients) were
      examined with the NIDEK Confoscan 3 confocal microscope before and 6 months after
      PRK and LASIK. The preoperative mean myopia was -2.85+/-0.99 diopters (D) (range:
      -1.00 to -4.00 D) in 24 eyes that underwent PRK and -2.94+/-0.96 D (range: -2.00
      to -4.25 D) in 8 eyes that underwent LASIK. Keratocyte density in the anterior
      and posterior stroma and the endothelial cell count were measured. Statistically
      significant changes were assessed using the t test. P<.05 was considered
      statistically significant. RESULTS: Preoperative hexagonal cell percentage in the
      LASIK group was 52.17+/-11.43 and 51.33+/-10.98 in the PRK group.
      Postoperatively, the percentages were 52.96+/-7.55 and 53.34+/-10.2,
      respectively. Six months postoperatively, keratocyte density changed by 367.12+/
      103.35 cells/mm(2) (34.7% reduction) in the anterior stroma (P<.05) and 9.25+/
      28.28 cells/mm(2) (1.31% reduction) in the posterior stroma (P>.05) for the LASIK
      group. In the PRK group, these values were 319.71+/-83.45 cells/mm(2) (31.13%
      reduction) in the anterior stroma (P<.05) and 0.17+/-38.97 cells/mm(2) (0.02%
      reduction) in the posterior stroma (P>.05). The changes in keratocyte densities
      were not statistically significant between groups (P>.05). The mean number of
      keratocytes decreased by 37.2% in the retroablation zone of the LASIK group
      (P<.05). No changes were noted in endothelial cell counts. CONCLUSIONS: A
      significant decrease occurred in the number of stromal keratocytes in the
      anterior stroma. Despite differences in surgery, the change in keratocyte density
      and endothelial cell counts were similar between LASIK and PRK groups (P>.05).

PMID- 19848381
TI  - Electric field poled organic electro-optic materials: state of the art and future
      prospects.

PMID- 19848382
TI  - Substituted heterocyclic naphthalene diimides with unexpected acidity. Synthesis,
      properties, and reactivity.
AB  - Naphthalene bisimides (NDIs) with a heterocyclic 1,4-dihydro-2,3-pyrazinedione
      moiety have been synthesized from both 2,6-dibromonaphthalene and 2,3,6,7
      tetrabromonaphthalene bisanhydrides by means of a stepwise protocol including
      imidization, nucleophilic displacement of the bromine atoms by ethane-1,2
      diamine, in situ reductive dehalogenation, and further oxidation. These
      heterocycles (R = n-pentyl, cyclohexyl) are yellow dyes with green emission in
      organic solvent, where the acid form dominates. The orange nonfluorescent
      conjugate base can be generated quantitatively by CH(3)COONBu(4) addition in
      DMSO, where it exhibits a pK(a) = 7.63. The conjugate base becomes the only
      detectable species (by UV-vis spectroscopy), in water solution, even under acid
      conditions (pH 1). In aqueous DMSO the acid/base equilibrium is a function of the
      DMSO/water ratio. The unexpected acidity of these heterocyclic NDIs, which
      justifies the reactivity with CH(2)N(2), has been rationalized by DFT
      computational means [PBE0/6-31+G(d,p)] in aqueous solvent (PCM models) as a
      result of a strong specific solvation effect, modeled by the inclusion of three
      water molecules.

PMID- 19848383
TI  - Synthesis, characterization, and rotational dynamics of crystalline molecular
      compasses with N-heterocyclic rotators.
AB  - We describe in this paper the synthesis, crystallization, and solid-state NMR
      dynamics of molecules intended to emulate the structure and function of
      macroscopic compasses. The desired structures consist of polar pyridine (2) and
      pyridazine (3) groups as well as their corresponding N-oxides (2O and 3O), each
      linked axially to two bulky triphenyl methyl groups by 1,4-triple bonds. The
      structures are such that the central polar heterocycles may rotate about the
      dialkyne axle while being sterically shielded by the two trityl groups. In
      addition to the synthesis of samples with natural isotopic abundance, we describe
      the preparation of 2-d(2) and 3-d(30), one labeled with deuteria in the pyridine
      rotator and the other fully deuterated in the two trityl groups in the stator.
      Crystal structures of 2 and 3 revealed packing motifs analogous to those
      previously reported for samples prepared with substituted phenylene rotators.
      While solid-state NMR measurements by (13)C CPMAS NMR revealed insufficient
      chemical shift dispersion for a dynamic characterization of the rotation of
      compounds 2 and 3 (including 3-d(30)), the use of quadrupolar echo (2)H NMR
      methods with 2-d(2) revealed a rotational site exchange with a barrier of ca. 8.5
      kcal/mol (35.5 kJ mol(-1)) for the pyridine group in 2.

PMID- 19848384
TI  - Palladium-catalyzed intramolecular 5-exo-dig hydroarylations of N
      arylpropiolamides: thermodynamics-controlled stereoselective synthesis of 3
      methyleneoxindoles.
AB  - Palladium-catalyzed intramolecular hydroarylation of N-arylpropiolamides has been
      developed for the stereoselective synthesis of 3-(monosubstituted
      methylene)oxindoles. In the presence of Pd(OAc)(2) and dppf, a variety of N
      arylpropiolamides successfully underwent the intramolecular hydroarylation
      reaction to afford the corresponding 3-(monosubstituted-methylene)oxindoles in
      moderate to excellent yields. It is noteworthy that the stereoselectivity of the
      reaction can be controlled by varying the reaction temperature.

PMID- 19848385
TI  - Synthesis of conformationally constrained diaminodicarboxylic acid derivatives.
AB  - Functionally protected forms of three conformationally constrained
      diaminodicarboxylic acids were synthesized and characterized. 2,2'
      Diaminospiro[3.3]heptane-2,2'-dicarboxylic acid, an analogue of diaminopimelic
      acid, was prepared in racemic form and the structure established by X-ray
      crystallographic analysis of the methyl ester hydrochloride. trans-1,4
      Diaminocyclohexane-1,4-dicarboxylic acid was prepared and its structure
      established by X-ray crystallographic analysis of the corresponding Cbz-protected
      ethyl ester. cis- and trans-2,6-diamino-1,2,3,5,6,7-hexahydro-s-indacene-2,6
      dicarboxylic acids were synthesized and the structures assigned by X-ray
      crystallographic analysis of the corresponding Boc-protected ethyl ester and Cbz
      protected ethyl ester, respectively.

PMID- 19848386
TI  - The Au(I)-catalyzed intramolecular hydroarylation of terminal alkynes under mild
      conditions: application to the synthesis of 2H-chromenes, coumarins, benzofurans,
      and dihydroquinolines.
AB  - Operationally simple Au(I)-catalyzed intramolecular hydroarylation (IMHA)
      reactions of terminal alkynes that proceed in high yield and under very mild
      conditions are described. These processes involve low catalyst loadings, mild
      reaction temperatures, and short reaction times, require no cocatalysts or
      additives, and allow for the generation of a number of important heterocyclic
      motifs from readily accessible starting materials.

PMID- 19848387
TI  - Biodiversity of exopolysaccharides produced from sucrose by sourdough lactic acid
      bacteria.
AB  - The distribution and diversity of natural exopolysaccharides (EPS) produced from
      sucrose by thirty heterofermentative lactic acid bacteria strains from French
      traditional sourdoughs was investigated. The EPS production was found to be
      related to glucansucrase and fructansucrase extracellular activities. Depending
      on the strain, soluble and/or cell-associated glycansucrases were secreted.
      Structural characterization of the polymers by 1H and 13C NMR spectroscopy
      analysis further demonstrated a high diversity of EPS structures. Notably, we
      detected strains that synthesize glucans showing amazing variations in the amount
      of alpha-(1-->2), alpha-(1-->3) and alpha-(1-->6) linkages. The representation of
      Leuconostoc strains which produce putative alternan polymers and alpha-(1-->2)
      branched polymers was particularly high. The existence of glucan- and
      fructansucrase encoding genes was also confirmed by PCR detection. Sourdough was
      thus demonstrated to be a very attractive biotope for the isolation of lactic
      acid bacteria producing novel polymers which could find interesting applications
      such as texturing agent or prebiotics.

PMID- 19848388
TI  - Effect of the solvent type and temperature on phytosterol contents and
      compositions of wheat straw, bran, and germ extracts.
AB  - Wheat fractions, such as bran, germ, and straw, are rich in a number of health
      beneficial bioactive compounds. However, they have not been exploited to their
      full capacity for value-added product development. This study examines the
      potential of recovering phytosterol (PS)-enriched extracts from wheat germ, bran,
      and straw. The main objective of the study was to evaluate the effect of solvent
      type and temperature on PS content and composition in straw, bran, and germ
      extracts. Petroleum ether, chloroform, n-hexane, and ethanol were used as
      solvents. A pressurized solvent extraction system was used for extraction of
      wheat fractions. Germ extracts had the highest total PS content followed by straw
      and bran extracts. Beta-sitosterol, campesterol, and stigmasterol were the main
      PSs in all of the extracts. Ethanol extraction resulted in the lowest total PS
      recovery from germ. Solvent type had a significant effect on PS composition in
      straw extracts. beta-Sitosterol was the most abundant PS in straw hexane extracts
      (74% of total PS). Petroleum ether, chloroform, and ethanol extracted more
      stigmasterol than beta-sitosterol from straw. This study demonstrated that the
      solvent type and temperature had significant effects on both PS content and
      composition of extracts collected from wheat fractions. Because of the complex
      nature of the agricultural materials, solvent selection and process optimization
      need to be based on experimental data. Pressurized solvent extraction is a useful
      technique to screen complex biological materials for their composition and to
      determine processing conditions to be optimized.

PMID- 19848390
TI  - cis- versus trans-ceramides: effects of the double bond on conformation and H
      bonding interactions.
AB  - Natural ceramides (Cers) possess a trans double bond between C4 and C5 of the
      sphingoid chain. This double bond is critical to their cell signaling properties.
      Both a change from trans to cis and the saturation of this site lead to changes
      in or loss of biological activity. To explore the conformational impact of the
      cis double bond, through-bond, and through-space interactions were investigated
      in hydrated Cers by multidimensional (1)H and (13)C NMR spectroscopy. Unlike
      trans-Cer, the cis-isomer exhibited not one but two broad yet resolved resonances
      for the protons in C1-OH and C3-OH, much like dihydroceramide (DHCer).
      Temperature-dependent studies and partial isotopic labeling of cis-Cer revealed
      that relative to trans-Cer, these two OH groups form weaker hydrogen bonds,
      particularly in the case of C1-OH. Our results also suggest that the cis double
      bond twists, slightly, the orientation of HO-C1 with respect to HO-C3, thus
      weakening the hydrogen-bonding network formed between the two OH groups of cis
      Cer and bound water molecules. The alteration of the local network of H-bonds may
      account for the differences observed in the biological activity of the two
      isomers.

PMID- 19848389
TI  - Effects of three different highly purified n-3 series highly unsaturated fatty
      acids on lipid metabolism in C57BL/KsJ-db/db mice.
AB  - Triglycerides (TG) consisting of highly purified (>97%) n-3 series highly
      unsaturated fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid
      (DPA), and docosahexaenoic acid (DHA), were administered to C57BL/KsJ-db/db mice
      for 4 weeks by pair-feeding to compare their effects on lipid metabolism and to
      evaluate the effects of DPA on lipid metabolism. The hepatic TG level and total
      amount was decreased by treatment with DHA and DPA compared to the control. The
      efficacy of DPA was greater than that of EPA, but less than that of DHA. In
      contrast, EPA had the greatest serum TG reducing effect. The hepatic cytosol
      fraction of the DHA-treated group contained the lowest fatty acid synthase (FAS)
      and malic enzyme (ME) activity levels. Furthermore, the DHA-treated group
      contained the highest serum adiponectin concentrations. These findings indicate
      that the strong hepatic TG-lowering effect of DHA is due to the suppression of TG
      synthesis. The same tendencies were observed in DPA-treated mice, and the effect
      was stronger than that observed in EPA-treated mice, but equivalent to that
      observed in DHA-treated mice. Based on these results, DPA possesses lipid
      metabolism-improving effects. The beneficial effects of DPA for lipid metabolism
      were not superior to those of EPA and DHA, and the effect was always intermediate
      between those of EPA and DHA.

PMID- 19848391
TI  - Counterion-induced changes to the micellization of surfactin-C16 aqueous
      solution.
AB  - The effects of counterions on surfactin-C(16) micelle solution with its critical
      micelle concentration (cmc), microenvironment properties in micelles, micelle
      size distribution, and morphology were investigated by fluorescence, dynamic
      light-scattering, and freeze-fracture transmission electron microscopy
      measurements. Counterions enhanced the surface activity of surfactin-C(16) and
      reduced the cmc. With the micellization of surfactin-C(16), it adopted a beta
      sheet conformation, and univalent concentrations reduced micelle micropolarity,
      increased micelle microviscosity, and tended to cause formation of small and
      spherical micelles, while divalent counterions had a special effect. With low
      concentration of divalent cations, they had strong interaction with surfactin
      C(16) micelles and tended to form larger micelle aggregates.

PMID- 19848392
TI  - Crystallization kinetics of ultraviscous acetaminophen by heat capacity and
      enthalpy measurements and diffusion control.
AB  - Crystallization kinetics of ultraviscous acetaminophen has been studied at 308.2,
      318.2, and 328.2 K by measuring the heat capacity, C(p), and the heat release in
      real time up to a period of 2.5 days. C(p) decreases according to an inverted
      sigmoid-shape curve, and the heat released increases according to a similar
      shape. The extent of crystallization determined from the two measurements
      differs, thus indicating that the interfacial liquid's C(p) may be slightly
      different from that of the bulk liquid. Both the excess C(p) of the liquid over
      the crystal phase and the corresponding excess enthalpy decrease with decrease in
      the temperature. The kinetics of crystallization follows the Kolmogorov-Johnson
      Mehl-Avrami relation, alpha(cryst)(t) = 1 - exp(-kt(m)). The logarithm of the
      rate constant, ln k, increases from -40.78 at 308.2 K to -32.85 at 328.2 K, and m
      from 3.60 to 3.83. The product of k and the calorimetric relaxation time remains
      constant with changing temperature thus showing that the two are inversely
      related. This shows that crystallization may be diffusion-controlled in the
      ultraviscous melt. The C(p) data indicate that slow crystallization of melt
      produces acetaminophen's (monoclinic) form I. Several effects usually overlooked
      in the crystallized kinetics formalisms have been described.

PMID- 19848393
TI  - Framework stabilization of Ge-rich zeolites via postsynthesis alumination.
AB  - The use of organic structure directing agents in zeolite syntheses has
      dramatically extended the number of zeolite structure types during the past
      decades. However, for about 20% of all known zeolite structure types, the
      necessary postsynthesis elimination of organic templates by high-temperature
      combustion leads to structure collapse, where the particularly strongly affected
      are Ge-rich zeolites. Here, we present a treatment approach that leads to zeolite
      structure stabilization by postsynthetic isomorphous substitution of Al for Ge.
      An important advantage of this new method is that no preliminary elimination of
      the organic structure directing agent from zeolite pores is required; thus it can
      be applied to microporous materials that cannot withstand the high temperature
      combustion of organic templates. The experimental data unambiguously show that
      besides framework stabilization the postsynthesis treatment facilitates
      incorporation of active sites in the zeolite framework. The feasibility of this
      new approach is corroborated by alumination of a BEC-type material. The presented
      method is expected to broaden the practical utilization of many microporous
      materials by improving their thermal stability.

PMID- 19848394
TI  - Excited-state coordination chemistry: excited-state basicity of bis(2,2'
      bipyridyl)(2,3-dipyridylpyrazine)ruthenium(II).
AB  - The proton dependencies of the absorption and emission spectra of bis(2,2'
      bipyridyl)(2,3-bis(2-pyridyl)pyrazine)ruthenium(II), (bpy)(2)Ru(dpp)(2+) indicate
      that population of the dpp-localized MLCT state increases the basicity of dpp
      peripheral nitrogens. NMR spectra reveal the protonation of the peripheral dpp
      pyridine in the ground state, pK(a) of 1.12 +/- 0.03, occurs intermediate between
      the changes evident in the absorption and emission spectra. As a result, the
      emissivity of aqueous solutions of (bpy)(2)Ru(dpp)(2+) as a function of [H(+)]
      derives from two emissive species: the unprotonated complex and the
      monoprotonated complex [(bpy)(2)Ru(dppH(py))](3+) with the proton attached to the
      peripheral dpp pyridine. Although protonation in the MLCT state generally
      quenches the emission, the emissivity of the monoprotonated complex, albeit weak,
      is attributed to the asymmetric distribution of the charge in the MLCT state. The
      majority of the transferred charge resides at the peripheral pyrazinyl nitrogen,
      and excited-state acid-base chemistry occurs predominantly at this site.
      Nonetheless, ground-state protonation of the peripheral dpp pyridine dramatically
      increases the nonradiative decay rate and significantly influences subsequent
      excited-state protonation processes. Protonation of the excited state changes
      from a bimolecular process to a combination of inter- and intramolecular
      processes where the proton transfers from the dpp pyridyl nitrogen to the dpp
      pyrazinyl nitrogen and from the surrounding aqueous solvent shell. Energetically,
      changes in the absorption spectra originally attributed to the first protonation
      of the complex and from which the DeltapK(a) of the excited state have been
      estimated, in fact, correspond to the second protonation of the complex.

PMID- 19848395
TI  - Free electron transfer with bifunctional donors: p-aminotritylsilanes.
AB  - This work provides an in-depth look at the bimolecular free-electron transfer
      (FET) from bisubstituted (amine and -CR(2)SiMe(3) groups) aromatic molecules to
      the solvent radical cations of n-BuCl. Because of the low rotational barriers,
      the substrates obtain all possible arrangements in solution. The electron jump is
      an unhindered process that does not require a defined encounter complex. The
      resulting radical cations show great conformer diversity because they directly
      inherit the geometry of their mobile precursors. One part of the radical cations
      is unstable and dissociates instantly, but the other one is metastable
      (microsecond lifetime). The two substituents reduce the barrier of internal
      rotation, resulting in stabilization of the otherwise good leaving group 
      SiMe(3). The amine group governs the reactivity of the system because it receives
      most of the electron density of the fluctuating highest MOs: primary and
      secondary amine groups lead to both instant and delayed formation of aminyl
      radicals; tertiary amines cause the rapid loss of an alpha-H(+) to yield alpha
      aminoalkyl radicals.

PMID- 19848396
TI  - Experimental and theoretical analysis of the kinetics of the reaction of atomic
      bromine with 1,4-dioxane.
AB  - The rate coefficient for the reaction of atomic bromine with 1,4-dioxane was
      measured from approximately 300 to 340 K using the relative rate method. Iso
      octane and iso-butane were used as reference compounds, and the experiments were
      made in a bath of argon containing up to 210 Torr of O(2) at total pressures
      between 200 and 820 Torr. The rate coefficients were not affected by changes in
      pressure or O(2) concentration over our range of experimental conditions. The
      ratios of rate coefficients for the reaction of dioxane relative to the reference
      compound were put on an absolute basis by using the published absolute rate
      coefficients for the reference reactions. The variation of the experimentally
      determined rate coefficients with temperature for the reaction of Br with 1,4
      dioxane can be given by k(1)(exp)(T) = (1.4 +/- 1.0) x 10(-11)exp[-23.0 +/- 1.8)
      kJ mol(-1)/(RT)] cm(3) molecule(-1) s(-1). We rationalized our experimental
      results in terms of transition state theory with molecular data from quantum
      chemical calculations. Molecular geometries and frequencies were obtained from
      MP2/aug-cc-pVDZ calculations, and single-point energies of the stationary points
      were obtained at CCSD(T)/CBS level of theory. The calculations indicate that the
      1,4-dioxane + Br reaction proceeds in an overall endothermic addition-elimination
      mechanism via a number of intermediates. The rate-determining step is a chair-to
      boat conformational change of the Br-dioxane adduct. The calculated rate
      coefficients, given by k(1)(calc)(T) = 5.6 x 10(-11)exp[-26.6 kJ mol(-1)/(RT)]
      cm(3) molecule(-1) s(-1), are in very good agreement with the experimental
      values. Comparison with results reported for the reactions of Br with other
      ethers suggests that this multistep mechanism differs significantly from that for
      abstraction of hydrogen from other ethers by atomic bromine.

PMID- 19848397
TI  - Mechanisms of cascade reactions in the syntheses of camptothecin-family
      alkaloids: intramolecular [4(+) + 2] reactions of N-arylimidates and alkynes.
AB  - The key steps of cascade reactions employed in the syntheses of camptothecin
      family alkaloids by Fortunak and Yao are intramolecular aza-Diels-Alder (IADA)
      reactions between in situ generated N-arylimidates and alkynes. The efficiencies
      of the IADA reactions are different but not well-understood. DFT calculations
      shown here provide insights into these two IADA reactions and well-rationalize
      why hexaphenyloxodiphosphonium triflate (Hendrickson reagent) as an amide
      activating reagent is superior to trimethyloxonium fluoroborate.

PMID- 19848398
TI  - Dehydroeburicoic acid induces calcium- and calpain-dependent necrosis in human
      U87MG glioblastomas.
AB  - Dehydroeburicoic acid (DeEA) is a triterpene purified from medicinal fungi such
      as Antrodia camphorate, the crude extract of which is known to exert cytotoxic
      effects against several types of cancer cells. We aim to test the hypothesis that
      DeEA possesses significant cytotoxic effects against glioblastomas, one of the
      most frequent and malignant brain tumors in adults. 3-(4,5-Dimethyl-thiazol-2-yl)
      2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays
      indicated that DeEA inhibited the proliferation of the human glioblastoma cell
      U87MG. In addition, Annexin V and propidium iodide staining showed that DeEA
      treatment led to a rapid increase of glioblastomas in the necrotic/late apoptotic
      fraction, whereas cell cycle analysis revealed that DeEA failed to significantly
      enhance the population of U87MG cells in the hypodiploid (sub-G1) fraction. Using
      electron microscopy, we found that DeEA induced significant cell enlargements,
      massive cytoplasmic vacuolization, and loss of mitochondrial membrane integrity.
      DeEA treatment triggered an intracellular Ca(2+) increase, and DeEA-induced cell
      death was significantly attenuated by BAPTA-AM but not ethylenediaminetetraacetic
      acid or ethylene glycol tetraacetic acid. DeEA instigated a reduction of both
      mitochondrial transmembrane potential and intracellular ATP level. Moreover, DeEA
      induced proteolysis of alpha-spectrin by calpain, and DeEA cytotoxicity in U87MG
      cells was caspase-independent but was effectively blocked by calpain inhibitor.
      Interestingly, DeEA also caused autophagic response that was prevented by calpain
      inhibitor. Taken together, these results suggest that in human glioblastomas,
      DeEA induces necrotic cell death that involves Ca(2+) overload, mitochondrial
      dysfunction, and calpain activation.

PMID- 19848399
TI  - Evaporation and discharge dynamics of highly charged multicomponent droplets
      generated by electrospray ionization.
AB  - We investigate the Rayleigh discharge and evaporation dynamics of highly charged
      two-component droplets consisting principally of methanol with 2-methoxyethanol,
      tert-butanol, or m-nitrobenzyl alcohol. A phase Doppler anemometer (PDA)
      characterizes droplets generated by electrospray ionization (ESI) according to
      size, velocity, and charge as they move through a uniform electric field within
      an ion mobility spectrometer (IMS). Repeated field reversals result in droplet
      "ping-pong" through the PDA. This generates individual droplet histories of
      solvent evaporation behavior and the dynamics of charge loss to progeny droplets
      during Rayleigh discharge events. On average, methanol droplets discharge at 127%
      their Rayleigh limit of charge, q(R), and release 25% of the net charge. Charge
      loss from methanol/2-methoxyethanol droplets behaves similarly to pure 2
      methoxyethanol droplets which release approximately 28% of their net charge.
      Binary methanol droplets containing up to 50% tert-butanol discharge at a lower
      percent q(R) than pure methanol and release a greater fraction of their net
      charge. Mixed 99% methanol/1% m-nitrobenzyl alcohol droplets possess discharge
      characteristics similar to those of methanol. However, droplets of methanol
      containing 2% m-nitrobenzyl evaporate down to a fixed size and charge that
      remains constant with no observable discharges. Quasi-steady-state evaporation
      models accurately describe observed evaporation phenomena in which methanol/tert
      butanol droplets evaporate at a rate similar to that of pure methanol and
      methanol/2-methoxyethanol droplets evaporate at a rate similar to that of 2
      methoxyethanol. We compare these results to previous Rayleigh discharge
      experiments and discuss the implications for binary solvents in electrospray mass
      spectrometry (ESI-MS) and field-induced droplet ionization mass spectrometry
      (FIDI-MS).

PMID- 19848400
TI  - Gas-phase reactions of atomic lanthanide cations with ammonia: room-temperature
      kinetics and periodicity in reactivity.
AB  - Reactions of (14) atomic lanthanide cations (excluding Pm(+)) with ammonia have
      been surveyed in the gas phase by using an inductively coupled plasma/selected
      ion flow tube (ICP/SIFT) tandem mass spectrometer to measure rate coefficients
      and product distributions in He at 0.35 +/- 0.01 Torr and 295 +/- 2 K. Primary
      reaction channels were observed corresponding to H(2) elimination with formation
      of the protonated lanthanum nitride and NH(3) addition. H(2) elimination was seen
      only in the reactions with La(+), Ce(+), Gd(+), and Tb(+) and occurs with these
      ions exclusively. NH(3) addition was seen with Pr(+), Nd(+), Sm(+), Eu(+), Dy(+),
      Ho(+), Er(+), Tm(+), Yb(+), and Lu(+). Higher-order sequential addition of up to
      five NH(3) molecules was observed with the Ln(+)(NH(3)) and LnNH(+) ions. The
      reaction efficiency of the primary reactions is seen to decrease as the energy
      required to promote an electron to make two non-f electrons available for bonding
      increases. The periodic trend in reaction efficiency along the lanthanide series
      matches quite closely the periodic trend in the electron-promotion energy
      required to achieve a d(1)s(1) or d(2) excited electronic configuration in the
      lanthanide cation. With La(+), Ce(+), Gd(+), and Tb(+), the electrostatic
      attraction between the atomic lanthanide cation and ammonia is sufficiently
      strong to provide enough energy to achieve electron promotion and to overcome any
      barriers to subsequent N-H bond insertion and H(2) loss, but this is not the case
      with the other lanthanide cations with which collisional stabilization of the
      intermediate adduct ion, with or without insertion of Ln(+), predominates.

PMID- 19848401
TI  - Proton NMR of (15)N-choline metabolites enhanced by dynamic nuclear polarization.
AB  - Chemical shifts of protons can report on metabolic transformations such as the
      conversion of choline to phosphocholine. To follow such processes in vivo,
      magnetization can be enhanced by dynamic nuclear polarization (DNP). We have
      hyperpolarized in this manner nitrogen-15 spins in (15)N-labeled choline up to
      3.3% by irradiating the 94 GHz electron spin resonance of admixed TEMPO nitroxide
      radicals in a magnetic field of 3.35 T during ca. 3 h at 1.2 K. The sample was
      subsequently transferred to a high-resolution magnet, and the enhanced
      polarization was converted from (15)N to methyl- and methylene protons, using the
      small (2,3)J((1)H,(15)N) couplings in choline. The room-temperature lifetime of
      nitrogen polarization in choline, T(1)((15)N) approximately 200 s, could be
      considerably increased by partial deuteration of the molecule. This procedure
      enables studies of choline metabolites in vitro and in vivo using DNP-enhanced
      proton NMR.

PMID- 19848402
TI  - Synthesis and transfection properties of a series of lipidic neamine derivatives.
AB  - With the view to develop novel bioinspired nonviral vectors for gene delivery, we
      synthesized a series of cationic lipids with a neamine headgroup, which
      incorporates rings I and II of the natural antibiotic aminoglycoside neomycin B.
      Indeed, we reasoned that neamine might constitute a straightforward and versatile
      building block for synthesizing a variety of lipophilic aminoglycosides and
      modulating their characteristics such as size, topology, lipophilicity, number of
      charges, and charge density. Neamine derivatives bearing long dialkyl chains, one
      or two neamine headgroups, and four to ten protonatable amine functions were
      prepared through the selective alkylation of the 4'- or 5-hydroxyl function in
      ring I and ring II of neamine, respectively. The transfection activity of the
      twelve derivatives synthesized was investigated in vitro in gene transfection
      experiments using several mammalian cell lines. The results allowed us to unveil
      interesting structure-activity relationships and to identify a formulation
      incorporating a small neamine derivative as a highly efficient gene delivery
      system.

PMID- 19848403
TI  - Engineering an inward proton transport from a bacterial sensor rhodopsin.
AB  - ATP is synthesized by an enzyme that utilizes proton motive force, and thus,
      nature has created various proton pumps. The best-understood proton pump is
      bacteriorhodopsin (BR), an outward-directed, light-driven proton pump in
      Halobacterium salinarum. Many archaeal and eubacterial rhodopsins are now known
      to show similar proton transport activity. We previously converted BR into an
      inward-directed chloride ion pump, but an inward proton pump has never been
      created. Proton pumps must have a specific mechanism to exclude transport in the
      reverse direction in order to maintain a proton gradient, and in the case of BR,
      a highly hydrophobic cytoplasmic domain may constitute such machinery. Here we
      report that an inward-directed proton transport can be engineered from a
      bacterial rhodopsin by a single amino acid replacement. Anabaena sensory
      rhodopsin (ASR) is a photochromic sensor in freshwater cyanobacteria that
      possesses little proton pump activity. When we replaced Asp217 in the cytoplasmic
      domain (a distance of approximately 15 A from the retinal chromophore) by Glu,
      ASR exhibited an inward proton transport activity driven by absorption of a
      single photon. FTIR spectra clearly showed an increased proton affinity for
      Glu217, which presumably controls the unusual directionality opposite to that in
      normal proton pumps.

PMID- 19848404
TI  - Discovery of potent and selective inhibitors of the mammalian target of rapamycin
      (mTOR) kinase.
AB  - The mammalian target of rapamycin (mTOR) is a central regulator of cell growth,
      metabolism, and angiogenesis and an emerging target in cancer research. High
      throughput screening (HTS) of our compound collection led to the identification
      of 3-(4-morpholin-4-yl-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenol
      (5a), a modestly potent and nonselective inhibitor of mTOR and phosphoinositide 3
      kinase (PI3K). Optimization of compound 5a, employing an mTOR homology model
      based on an X-ray crystal structure of closely related PI3Kgamma led to the
      discovery of 6-(1H-indol-5-yl)-4-morpholin-4-yl-1-[1-(pyridin-3
      ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidine (5u), a potent and
      selective mTOR inhibitor (mTOR IC(50) = 9 nM; PI3Kalpha IC(50) = 1962 nM).
      Compound 5u selectively inhibited cellular biomarker of mTORC1 (P-S6K, P-4EBP1)
      and mTORC2 (P-AKT S473) over the biomarker of PI3K/PDK1 (P-AKT T308) and did not
      inhibit PI3K-related kinases (PIKKs) in cellular assays. These
      pyrazolopyrimidines represent an exciting new series of mTOR-selective inhibitors
      with potential for development for cancer therapy.

PMID- 19848406
TI  - Combination of FASP and StageTip-based fractionation allows in-depth analysis of
      the hippocampal membrane proteome.
AB  - Membrane proteomics is challenging because the desirable strong detergents are
      incompatible with downstream analysis. Recently, we demonstrated efficient
      removal of SDS by the filter aided sample preparation method (FASP). Here we
      combine FASP with our previously described small-scale membrane enrichment
      protocol. Analysis of a single mouse hippocampus enables identification of more
      than 1000 membrane proteins in a single LC-MS/MS run without protein or peptide
      prefractionation. To extend proteome coverage, we developed a simple anion
      exchange fractionation method in a StageTip format. When separating peptides into
      six fractions, a duplicate analysis resulted in identification of 4206 proteins
      of which 64% were membrane proteins. This data set covers 83% of glutamate and
      GABA receptor subunits identified in hippocampus in the Allen Brain Atlas and
      adds further isoforms. The combined method provides a streamlined protocol for
      rapid and sensitive membrane proteome mapping. We also provide a generic protocol
      for combining FASP with StageTip-based ion exchange fractionation, which is
      generally applicable to proteome analysis.

PMID- 19848405
TI  - Aza-peptidyl Michael acceptor and epoxide inhibitors--potent and selective
      inhibitors of Schistosoma mansoni and Ixodes ricinus legumains (asparaginyl
      endopeptidases).
AB  - Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala
      Ala-AAsn-trans-CH horizontal lineCHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively,
      are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from
      the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus
      (IrAE). Structure-activity relationships (SARs) were determined for a set of 41
      aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer
      disubstituted amides to monosubstituted amides in the P1' position, and potency
      increased as we increased the hydrophobicity of the inhibitor in this position.
      Extending the inhibitor to P5 resulted in increased potency, especially against
      IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza
      peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide
      inhibitors, and for some of these compounds, second-order inhibiton rate
      constants are the fastest yet discovered. Given the central functions of these
      enzymes in both parasites, the data presented here may facilitate the eventual
      design of selective antiparasitic drugs.

PMID- 19848407
TI  - Visible light generation of iodine atoms and I-I bonds: sensitized I(-) oxidation
      and I(3)(-) photodissociation.
AB  - Direct 355 or 532 nm light excitation of TBAI(3), where TBA is tetrabutyl
      ammonium, in CH(3)CN at room temperature yields an iodine atom, I(*), and an
      iodine radical anion, I(2)(-*). In the presence of excess iodide, the iodine atom
      reacts quantitatively to yield a second equivalent of I(2)(-*) with a rate
      constant of k = 2.5 +/- 0.4 x 10(10) M(-1) s(-1). The I(2)(-*) intermediates are
      unstable with respect to disproportionation and yield initial reactants, k = 3.3
      +/- 0.1 x 10(9) M(-1) s(-1). The coordination compound
      Ru(bpz)(2)(deeb)(PF(6))(2), where bpz is 2,2'-bipyrazine and deeb is 4,4'
      (C(2)H(5)CO(2))(2)-2,2'-bipyridine, was prepared and characterized for
      mechanistic studies of iodide photo-oxidation in acetonitrile at room
      temperature. Ru(bpz)(2)(deeb)(2+) displayed a broad metal-to-ligand charge
      transfer (MLCT) absorption band at 450 nm with epsilon = 1.7 x 10(4) M(-1) cm(
      1). Visible light excitation resulted in photoluminescence with a corrected
      maximum at 620 nm, a quantum yield phi = 0.14, and an excited state lifetime tau
      = 1.75 micros from which k(r) = 8.36 x 10(4) s(-1) and k(nr) = 5.01 x 10(5) s(-1)
      were abstracted. Arrhenius analysis of the temperature dependent excited state
      lifetime revealed an activation energy of approximately 2500 cm(-1) and a pre
      exponential factor of 10(10) s(-1), assigned to activated surface crossing to a
      ligand field or MLCT excited state. Steady state light excitation of
      Ru(bpz)(2)(deeb)(2+) in a 20 mM TBAI acetonitrile solution resulted in ligand
      loss photochemistry with a quantum yield of 5 x 10(-5). The MLCT excited state
      was dynamically quenched by iodide with K(sv) = 1.1 x 10(5) M(-1) and k(q) = 6.6
      +/- 0.3 x 10(10) M(-1) s(-1), a value consistent with diffusion-limited electron
      transfer. Excited state hole transfer to iodide was quantitative but the product
      yield was low due to poor cage escape yields, phi(CE) = 0.042 +/- 0.001.
      Nanosecond transient absorption was used to quantify the appearance of two
      photoproducts [Ru(bpz(-))(bpz)(deeb)](+) and I(2)(-*). The coincidence of the
      rate constants for [Ru(bpz(-))(bpz)(deeb)](+) formation and for excited state
      decay indicated reductive quenching by iodide. The rate constant for the
      appearance of I(2)(-*) was about a factor of 3 slower than excited state decay, k
      = 2.4 +/- 0.2 x 10(10) M(-1) s(-1), indicating that I(2)(-*) was not a primary
      photoproduct of excited state electron transfer. A mechanism was proposed where
      an iodine atom was the primary photoproduct that subsequently reacted with
      iodide, I(*) + I(-) --> I(2)(-*). Charge recombination Ru(bpz(-))(bpz)(deeb)(+) +
      I(2)(-*) --> Ru(bpz)(2)(deeb)(2+) + 2I(-) was highly favored, DeltaG(o) = -1.64
      eV, and well described by a second-order equal concentration kinetic model, k(cr)
      = 2.1 +/- 0.3 x 10(10) M(-1) s(-1).

PMID- 19848409
TI  - Modeling charge transport in organic photovoltaic materials.
AB  - The performance of an organic photovoltaic cell depends critically on the
      mobility of charge carriers within the constituent molecular semiconductor
      materials. However, a complex combination of phenomena that span a range of
      length and time scales control charge transport in disordered organic
      semiconductors. As a result, it is difficult to rationalize charge transport
      properties in terms of material parameters. Until now, efforts to improve charge
      mobilities in molecular semiconductors have proceeded largely by trial and error
      rather than through systematic design. However, recent developments have enabled
      the first predictive simulation studies of charge transport in disordered organic
      semiconductors. This Account describes a set of computational methods,
      specifically molecular modeling methods, to simulate molecular packing, quantum
      chemical calculations of charge transfer rates, and Monte Carlo simulations of
      charge transport. Using case studies, we show how this combination of methods can
      reproduce experimental mobilities with few or no fitting parameters. Although
      currently applied to material systems of high symmetry or well-defined structure,
      further developments of this approach could address more complex systems such
      anisotropic or multicomponent solids and conjugated polymers. Even with an
      approximate treatment of packing disorder, these computational methods simulate
      experimental mobilities within an order of magnitude at high electric fields. We
      can both reproduce the relative values of electron and hole mobility in a
      conjugated small molecule and rationalize those values based on the symmetry of
      frontier orbitals. Using fully atomistic molecular dynamics simulations of
      molecular packing, we can quantitatively replicate vertical charge transport
      along stacks of discotic liquid crystals which vary only in the structure of
      their side chains. We can reproduce the trends in mobility with molecular weight
      for self-organizing polymers using a cheap, coarse-grained structural simulation
      method. Finally, we quantitatively reproduce the field-effect mobility in
      disordered C60 films. On the basis of these results, we conclude that all of the
      necessary building blocks are in place for the predictive simulation of charge
      transport in macromolecular electronic materials and that such methods can be
      used as a tool toward the future rational design of functional organic electronic
      materials.

PMID- 19848408
TI  - Chemoselective cross-linking and functionalization of alginate via Staudinger
      ligation.
AB  - In this study, we demonstrate the applicability of functionalized alginate to
      serve as a platform for the covalent cross-linking or immobilization of
      complementary phosphine functionalized groups via the chemoselective Staudinger
      ligation scheme. Azide groups were covalently linked to alginate through a
      heterobifunctional polyethylene glycol (PEG) linker and carbodiimide. Degree of
      azide functionalization was varied as a function of carbodiimide concentration
      and determined by proton nuclear magnetic resonance ((1)H NMR) and infrared
      spectroscopy. Spontaneous and covalently cross-linked alginate-PEG gels were
      generated via the Staudinger ligation scheme upon incubation of the azide
      functionalized alginate with PEG chains having 1-methyl-2-diphenylphosphino
      terephthalate (MDT) as end groups. Modulation of the MDT to N(3) ratio resulted
      in variability of gel characteristics. In addition, azide functionalized alginate
      retained its capacity to instantaneously form hydrogels via electrostatic
      interaction with multivalent cations such as Ca(2+) and Ba(2+). Subsequently,
      covalent linkage of phosphine functionalized agents postgelation of the alginate
      was feasible, as illustrated via linkage of MDT-PEG-carboxyfluorescein.
      Capitalization of the chemoselective and cell compatible Staudinger ligation
      scheme for covalent cross-linking of alginate hydrogels may enhance the utility
      of this polymer for the stable encapsulation of various cell types, in addition
      to their use in the immobilization of labeling agents, proteins, and other
      bioactive molecules.

PMID- 19848410
TI  - Peptide retention standards and hydrophobicity indexes in reversed-phase high
      performance liquid chromatography of peptides.
AB  - The growing utility of peptide retention prediction in proteomics would benefit
      from the development of a universal peptide retention standard for better
      alignment of chromatographic data obtained using various liquid chromatography
      (LC) platforms. We describe a six-peptide mixture designed for this purpose; its
      members cover a wide range of hydrophobicity for the most popular modes of
      reversed-phase peptide high-performance liquid chromatography (HPLC): C18
      sorbents with trifluoroacetic/formic acid as the ion-pairing modifier and
      separations at pH 10. We propose a hydrophobicity index (HI) describing the
      concentration of organic solvent (typically acetonitrile) that yields a retention
      factor of 10 under isocratic elution conditions for any peptide. This measure is
      a fundamental characteristic of peptide-sorbent interaction, depending only on
      the type of sorbent and the ion-pairing modifier used. Spiking a sample with a
      standard peptide mixture provides a measurement of the HI values of all detected
      species during gradient separation. In addition to alignment of data and
      calibration of chromatographic runs when peptide retention prediction protocols
      are used, these values obtained from proteomics experiments can be utilized
      directly in method development for large-scale preparative separations.

PMID- 19848411
TI  - Online hydrogen/deuterium exchange performed in the ion mobility cell of a hybrid
      mass spectrometer.
AB  - The present paper describes the performance of online, gas-phase
      hydrogen/deuterium exchange implemented in the ion mobility cell of a quadrupole
      time-of-flight mass spectrometer. Deuterium oxide and deuterated methanol were
      utilized to create deuterated vapor that is introduced into the ion mobility
      region of the mass spectrometer. Hydrogen/deuterium exchange occurs spontaneously
      in the milliseconds time frame without the need of switching the instrument into
      ion mobility mode. The exchange was studied in case of low molecular weight
      molecules and proteins. The observed number of exchanged hydrogens was equal to
      the number of theoretically exchangeable hydrogens for all low molecular weight
      compounds. This method needs only minimal instrumental modifications, is simple,
      cheap, environment friendly, compatible with ultraperformance liquid
      chromatography, and can be implemented on commercially available instruments. It
      does not compromise choice of liquid chromatographic solvents and accurate mass
      or parallel-fragmentation (MS(E)) methods. The performance of this method was
      compared to that of conventional alternatives where the deuterated solvent is
      introduced into the cone gas of the instrument. Although the degree of exchange
      was similar between the two methods, the "cone gas method" requires 10 times
      higher deuterated solvent volumes (50 muL/min) and offers reduced sensitivity in
      the tandem mass spectrometry (MS/MS) mode. The presented method is suggested as a
      standard future element of mass spectrometers to aid online structural
      characterization of unknowns and to study conformational changes of proteins with
      hydrogen/deuterium exchange.

PMID- 19848412
TI  - NanoLC-MS/MS analyses of urinary desmosine, hydroxylysylpyridinoline and
      lysylpyridinoline as biomarkers for chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is a common and potentially lethal
      complication of allogeneic hematopoietic stem cell transplantation (HSCT). cGVHD
      as well as the transplant procedure itself (chemotherapy with or without
      radiotherapy) can lead to the degradation of connective tissue components such as
      elastin and collagen. The catabolism of these structural proteins releases
      desmosine (DES), lysylpyridinoline (LP), hydroxylysylpyridonoline (HP), and
      related pyridinium-based cross-linkers analogues that could represent potential
      biomarkers for cGVHD. This study reports the development of a sensitive liquid
      chromatography/tandem mass spectrometry method for the simultaneous analysis of N
      propyl derivatives of DES, HP, and LP. The concentrations of free and total forms
      of urinary DES, HP, and LP were determined using synthetic deuterated internal
      standards. This method enabled accurate quantitation of these pyridinium-based
      cross-linkers from as little as 100 microL of urine with detection limits of 0.03
      0.10 ng/mL. These compounds were analyzed in urine samples from three groups of
      patients: (1) Healthy volunteers, (2) Autologous HSCT recipients (who cannot
      develop cGVHD), and (3) Allogeneic HSCT recipients at onset of cGHVD. These
      analyses revealed that the urinary concentrations of DES, HP, and LP in the
      autologous recipients were greater or equal to the cGVHD group although both
      groups showed marked increase in the levels of these compounds compared to
      healthy individuals. These results suggest that the chemotherapy treatment has
      significant effects on the turnover of elastin and collagen, and that these
      biomarkers could be effective during prospective analyses to determine the onset
      of cGVHD.

PMID- 19848413
TI  - Label-free quantitation of a cancer biomarker in complex media using silicon
      photonic microring resonators.
AB  - Recent advances in label-free biosensing techniques have shown the potential to
      simplify clinical analyses. With this motivation in mind, this paper demonstrates
      for the first time the use of silicon-on-insulator microring optical resonator
      arrays for the robust and label-free detection of a clinically important protein
      biomarker in undiluted serum, using carcinoembryonic antigen (CEA) as the test
      case. We utilize an initial-slope-based quantitation method to sensitively detect
      CEA at clinically relevant levels and to determine the CEA concentrations of
      unknown samples in both buffer and undiluted fetal bovine serum. Comparison with
      a commercial enzyme-linked immunosorbent assay (ELISA) kit reveals that the label
      free microring sensor platform has a comparable limit of detection (2 ng/mL) and
      superior accuracy in the measurement of CEA concentration across a 3 order of
      magnitude dynamic range. Notably, we report the lowest limit of detection to date
      for a microring resonator sensor applied to a clinically relevant cancer
      biomarker. Although this report describes the robust biosensing capabilities of
      silicon photonic microring resonator arrays for a single parameter assay, future
      work will focus on utilizing the platform for highly multiplexed, label-free
      bioanalysis.

PMID- 19848414
TI  - Assembly of hybrid bacteriophage Qbeta virus-like particles.
AB  - Bacteriophage Qbeta coat protein forms uniform virus-like particles when
      expressed recombinantly in a variety of organisms. We have inserted the IgG
      binding Z domain at the carboxy terminus of the coat protein and coexpressed this
      chimeric subunit with native coat protein to create hybrid, IgG-binding virus
      like particles. Extracellular osmolytes were found to have an effect on the
      efficiency of incorporation of fusion proteins into VLPs in Escherichia coli when
      a carbenicillin, but not a kanamycin, selection marker was used. The addition of
      sucrose to the growth medium decreased the incorporation efficiency; the
      osmoprotectant glycine betaine eliminated this effect. The decrease in efficiency
      was not observed when carbenicillin was omitted from the final expression
      culture. The addition of sodium chloride instead of sucrose gave rise to
      particles with a larger number of fusion proteins than the standard conditions.
      These results illustrate that cellular conditions should be taken into account
      even in apparently simple systems when natural or engineered protein
      nanoparticles are made.

PMID- 19848415
TI  - Stratification and monitoring of juvenile idiopathic arthritis patients by
      synovial proteome analysis.
AB  - Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of
      chronic, childhood onset, autoimmune diseases with variable clinical outcomes. We
      investigated whether profiling of the synovial fluid (SF) proteome by a
      fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish
      patients in whom inflammation extends to affect a large number of joints, early
      in the disease process. SF samples from 22 JIA patients were analyzed: 10 with
      oligoarticular arthritis, 5 extended oligoarticular and 7 polyarticular disease.
      SF samples were labeled with Cy dyes and separated by two-dimensional
      electrophoresis. Multivariate analyses were used to isolate a panel of proteins
      which distinguish patient subgroups. Proteins were identified using MALDI-TOF
      mass spectrometry with expression further verified by Western immunoblotting and
      immunohistochemistry. Hierarchical clustering based on the expression levels of a
      set of 40 proteins segregated the extended oligoarticular from the oligoarticular
      patients (p < 0.05). Expression patterns of the isolated protein panel have also
      been observed over time, as disease spreads to multiple joints. The data
      indicates that synovial fluid proteome profiles could be used to stratify
      patients based on risk of disease extension. These protein profiles may also
      assist in monitoring therapeutic responses over time and help predict joint
      damage.

PMID- 19848419
TI  - Autobiography of Walter Thiel.

PMID- 19848416
TI  - Tissue proteomics reveals differential and compartment-specific expression of the
      homologs transgelin and transgelin-2 in lung adenocarcinoma and its stroma.
AB  - Discovery of tissue-specific biomarkers for human cancer is crucial for early
      diagnosis and molecular understanding of the disease. To overcome the limitations
      posed by the large dynamic concentration range and compositional complexity of
      tissue biomacromolecules, we applied heparin affinity fractionation for proteomic
      enrichment. Comparing the proteomes of five paired samples of normal lung and
      pulmonary adenocarcinoma tissue by 2-D difference gel electrophoresis, 14 spots
      were found to be differentially expressed. From these candidate spots, three
      proteins overexpressed in cancer were identified by mass spectrometry as
      transgelin (TAGLN, SM22-alpha, WS3-10), transgelin-2 (TAGLN2), and cyclophilin A
      (PPIA). Quantitative RT-PCR indicated that both TAGLN2 and PPIA were upregulated
      at the transcriptional level. Differential protein expression levels were
      validated by Western blot analysis using an independent set of 10 paired lung
      adenocarcinoma samples. Using immunohistochemistry on human tissue sections, we
      discovered that overexpression of TAGLN was strictly localized to the tumor
      induced reactive myofibroblastic stromal tissue compartment, whereas
      overexpression of TAGLN2 was exclusively localized to the neoplastic glandular
      compartment. Thus, the highly homologous protein pair TAGLN and TAGLN2 displayed
      mutually exclusive, compartment-specific cell type expression regulation in tumor
      stroma vs neoplastic epithelial cells. Our data further suggest that TAGLN may be
      a marker of active stromal remodeling in the vicinity of invasive carcinomas. It
      may shed light on mechanisms of tumor-stroma interaction and could be useful for
      early diagnosis, treatment guidance, and treatment response monitoring.

PMID- 19848422
TI  - Publications of walter thiel.

PMID- 19848417
TI  - Tryptophan synthase: structure and function of the monovalent cation site.
AB  - The monovalent cation (MVC) site of the tryptophan synthase from Salmonella
      typhimurium plays essential roles in catalysis and in the regulation of substrate
      channeling. In vitro, MVCs affect the equilibrium distribution of intermediates
      formed in the reaction of l-Ser with the alpha(2)beta(2) complex; the MVC-free,
      Cs(+)-bound, and NH(4)(+)-bound enzymes stabilize the alpha-aminoacrylate
      species, E(A-A), while Na(+) binding stabilizes the l-Ser external aldimine
      species, E(Aex(1)). Two probes of beta-site reactivity and conformation were used
      herein, the reactive indole analogue, indoline, and the l-Trp analogue, l-His.
      MVC-bound E(A-A) reacts rapidly with indoline to give the indoline quinonoid
      species, E(Q)(indoline), which slowly converts to dihydroiso-l-tryptophan. MVC
      free E(A-A) gives very little E(Q)(indoline), and turnover is strongly impaired;
      the fraction of E(Q)(indoline) formed is <3.5% of that given by the Na(+)-bound
      form. The reaction of l-Ser with the MVC-free internal aldimine species, E(Ain),
      initially gives small amounts of an active E(A-A) which converts to an inactive
      species on a slower, conformational, time scale. This inactivation is abolished
      by the binding of MVCs. The inactive E(A-A) appears to have a closed beta-subunit
      conformation with an altered substrate binding site that is different from the
      known conformations of tryptophan synthase. Reaction of l-His with E(Ain) gives
      an equilibrating mixture of external aldimine and quinonoid species, E(Aex)(his)
      and E(Q)(his). The MVC-free and Na(+) forms of the enzyme gave trace amounts of
      E(Q)(his) ( approximately 1% of the beta-sites). The Cs(+) and NH(4)(+) forms
      gave approximately 17 and approximately 14%, respectively. The reactivity of MVC
      free E(Ain) was restored by the binding of an alpha-site ligand. These studies
      show MVCs and alpha-site ligands act synergistically to modulate the switching of
      the beta-subunit from the open to the closed conformation, and this switching is
      crucial to the regulation of beta-site catalytic activity. Comparison of the
      structures of Na(+) and Cs(+) forms of the enzyme shows Cs(+) favors complexes
      with open indole binding sites poised for the conformational transition to the
      closed state, whereas the Na(+) form does not. The beta-subunits of Cs(+)
      complexes exhibit preformed indole subsites; the indole subsites of the open
      Na(+) complexes are collapsed, distorted, and too small to accommodate indole.

PMID- 19848423
TI  - Toward a wave-function-based treatment of metals: extrapolation from finite
      clusters.
AB  - High-level ab initio coupled-cluster results with up to quadruple-zeta basis sets
      are presented for small Be and Mg clusters that are sections of the bulk lattice.
      It is shown that in combination with density functional calculations these
      results allow for a reliable extrapolation toward the cohesive energy of the
      infinite solid.

PMID- 19848424
TI  - Ab initio thermochemistry with high-level isodesmic corrections: validation of
      the ATOMIC protocol for a large set of compounds with first-row atoms (H, C, N,
      O, F).
AB  - The recently proposed ATOMIC protocol is a fully ab initio thermochemical
      approach designed to provide accurate atomization energies for molecules with
      well-defined valence structures. It makes consistent use of the concept of bond
      separation reactions to supply high-level precomputed bond increments which
      correct for errors of lower-level models. The present work extends the approach
      to the calculation of standard heats of formation and validates it by comparison
      to experimental and benchmark level ab initio data reported in the literature.
      Standard heats of formation (298 K) have been compiled for a large sample of 173
      neutral molecules containing hydrogen and first-row atoms (C, N, O, F), resorting
      to several previous compilations and to the original experimental literature.
      Statistical evaluation shows that the simplest implementation of the ATOMIC
      protocol (composite model C) achieves an accuracy comparable to the popular
      Gaussian-3 approach and that composite models A and B perform better. Chemical
      accuracy (1-2 kcal/mol) is normally achieved even for larger systems with about
      10 non-hydrogen atoms and for systems with charge-separated valence structures,
      bearing testimony to the robustness of the bond-separation reaction model.
      Effects of conformational averaging have been examined in detail for the series
      of n-alkanes, and our most refined composite model A reproduces experimental
      heats of formation quantitatively, provided that conformational averaging is
      properly accounted for. Several cases of larger discrepancy with respect to
      experiment are discussed, and potential weaknesses of the approach are
      identified.

PMID- 19848425
TI  - Calculation of electronic g-tensors using coupled cluster theory.
AB  - A scheme for the calculation of the electronic g-tensor at the coupled cluster
      (CC) level is presented. The reported implementation employs an effective one
      electron spin-orbit operator, allows the inclusion of arbitrary excitations in
      the cluster operator, and offers various options concerning the treatment of
      orbital relaxation and choice of reference determinants. In addition, the use of
      gauge-including atomic orbitals (GIAOs) is possible to overcome the gauge origin
      problem. Benchmark calculations for the NH ((3)Sigma(-)) radical reveal the
      importance of electron correlation effects for the accurate prediction of the g
      shift as well as the slow basis set convergence of such calculations, which is
      only marginally improved by using GIAOs. CC singles and doubles results for the g
      tensor are furthermore used to validate various functionals often used in density
      functional theory calculations. At least for radicals containing only light
      elements, the B3LYP hybrid functional appears to be the best among the four
      functionals tested in the present work.

PMID- 19848426
TI  - Axial bonding in alkylcobalamins: DFT analysis of the inverse versus normal trans
      influence.
AB  - Density functional theory has been applied to study the origin of the inverse and
      normal trans influence in alkylcobalamins. In order to cover the X-ray structural
      data available for alkylcobalamins with a variety of axial substituents,
      geometries of 28 related corrin-containing models have been optimized and
      analyzed. The BP86/6-31G(d) level of theory was applied which showed good
      reliability in reproducing the axial bond lengths. Comparison of experimental and
      calculated data allowed to conclude that the inverse trans influence is not a
      general feature of cobalamins, as it appeared from the experimental data analysis
      alone. Inverse trans influence is observed for the series of R groups with
      increasing bulk and electron donating ability. For the series of R groups having
      similar medium bulk, but differing significantly in the electron donating
      ability, normal trans influence was found. Finally, it was determined, that the
      axial bond lengths correlate well but differently in the two series of R groups
      with the orbital energies of the six molecular orbitals essential in axial
      interligand bonding.

PMID- 19848427
TI  - Accurate potential energy surface and calculated spectroscopic properties for
      CdH2 isotopomers.
AB  - Ab initio calculations employing the coupled cluster method CCSD(T), in
      conjunction with a small-core pseudopotential for the cadmium atom, have been
      employed to construct a near-equilibrium potential energy function (PEF) and an
      electric dipole moment function (EDMF) for CdH(2). The significance of the spin
      orbit interaction was checked and found to be of minor importance. Making use of
      two pieces of experimental information for the most abundant isotopomer
      (114)CdH(2), we obtained a refined PEF, which, within variational calculations of
      rovibrational states and wave functions, reproduces all available experimental
      data (S. Yu, A.Shayesteh, and P. F. Bernath, J. Chem. Phys. 2005, 122, 194301)
      very well. In addition, numerous predictions are made. In particular, the nu(2)
      band origins for (114)CdH(2) and (114)CdD(2) are predicted at 605.9 and 436.9 cm(
      1), respectively, and the state perturbing the e parity levels of the (0,0(0),1)
      state of (114)CdH(2) at J = 12-17 is identified as the (0,3(3),0) state.
      Assignments for further perturbations found in the emission spectra are given as
      well.

PMID- 19848428
TI  - Thermochemistry of Pt-fullerene complexes: semiempirical study.
AB  - Modified Neglect of Differential Overlap (MNDO) and MNDO/d based semiempirical
      methods are widely employed to explore structure and thermochemistry of molecular
      systems. In this work, the AM1/d method has been parametrized for systems
      containing platinum. The proposed scheme delivers excellent performance for
      binding energies of Pt complexes with ethylene and large pi conjugated
      hydrocarbons. The estimated bond energies accurately reproduce the results of
      MP4(SDQ) calculations and show significant improvement over DFT (B3LYP and M05)
      data. We apply the AM1/d scheme to explore the structure and thermochemistry of
      several Pt compounds with C(60) and C(70). The calculated binding energies of
      bare Pt atoms and [Pt(PH(3))(2)] units to the fullerenes are 75 and 45 kcal/mol,
      respectively. We find that coordination of a single metal center to C(60)
      activates the fullerene cage making subsequent coordination of Pt more favorable.
      The bond energy [C(60)-PtC(60)] is calculated to be 65 kcal/mol. The estimated
      reaction enthalpies are useful for exploring the stability of Pt(x)C(60) polymer
      systems and their interaction with phosphines. AM1/d predicts a very low barrier
      to rotation of the coordinated fullerenes in [Pt(C(60))(2)]. The AM1/d scheme is
      computationally very efficient and can be employed to obtain fast quantitative
      estimates for binding energies and structural parameters of Pt complexes with
      large pi conjugated systems like fullerenes and carbon nanotubes.

PMID- 19848429
TI  - Local hybrid functionals with an explicit dependence on spin polarization.
AB  - A new family of local hybrid functionals with a position-dependent mixture of
      local and exact exchange has been constructed. On the basis of conceptual
      similarities between local hybrids and explicit nondynamical correlation
      functionals, the relative spin polarization has been introduced as an additional
      variable into the local mixing function (LMF) that determines the position
      dependence of the exact exchange admixture. This leads to two new two-parameter
      LMFs, one based on the ratio of the local kinetic energy density to the von
      Weizsacker kinetic energy density and the other on the dimensionless density
      gradient. After optimization of the two free parameters for small test sets,
      significant improvements of atomization energies of the full G3 set are obtained
      (mean absolute errors of 2.96 and 3.18 kcal mol(-1), respectively), with minor
      deterioration for classical reaction barriers (HTBH38 and NHTBH38 test sets). The
      simultaneous description of two-center three-electron dimer cations remains a
      challenge. It is shown that the exact and local spin density exchange energy
      densities have closely related gauge definitions, so that gauge mismatch is only
      a minor problem for local hybrids based on local exchange.

PMID- 19848430
TI  - O2 activation in a dinuclear Fe(II)/EDTA complex: spin surface crossing as a
      route to highly reactive Fe(IV)oxo species.
AB  - We study the cleavage of O2 in gas phase [(EDTAH)Fe(O2)Fe(EDTAH)]2-, a proposed
      intermediate in the aqueous Fe(II)-to-Fe(III) autoxidation reaction in the
      presence of atmospheric dioxygen and EDTA ligand. The role of the exchange
      coupling between the locally high-spin Fe centers in the O-O dissociation is
      investigated. Using results from broken symmetry (BS) density functional theory
      (DFT) calculations, we show that the system can be modeled as two high-spin (HS)
      S = 5/2 Fe(III) d5 centers coupled through a bridging peroxo O2(2-) ligand,
      consistent with hypotheses advanced in the literature. We show that in this
      electronic configuration the O-O cleavage reaction is forbidden by (spin)
      symmetry. Dissociation of the O2(2-) group to the product ground state may only
      take place if the system is allowed to undergo a transition to a state of lower
      spin multiplicity (S = 4) as the O-O bond is stretched. We show that the exchange
      coupling between the two Fe ions in [(EDTAH)Fe(O2)Fe(EDTAH)]2- plays only a minor
      role in defining the chemistry of O2 activation in this system. The peroxo/oxo
      interconversion involves a state outside the Heisenberg spin ladder of the
      initial S = 5 state. In this S = 4 state, the dinuclear complex evolves to two
      oxo complexes, [EDTAH x Fe(IV)O]-, with an overall energy barrier of only
      approximately 86 kJ mol(-1). According to recent theoretical work, the latter
      species are exceptionally strong oxidants, making them ideal candidate catalysts
      for organic oxidations (including C-H bond hydroxylation). We highlight the
      (spin) symmetry forbidden nature of the reaction on the S = 5 surface and its
      symmetry allowed character in the electronic configuration with S = 4.

PMID- 19848431
TI  - Are current semiempirical methods better than force fields? A study from the
      thermodynamics perspective.
AB  - The semiempirical Hamiltonians MNDO, AM1, PM3, RM1, PDDG/MNDO, PDDG/PM3, and SCC
      DFTB, when used as part of a hybrid QM/MM scheme for the simulation of biological
      molecules, were compared on their abilities to reproduce experimental ensemble
      averages at or near room temperatures for the model system alanine dipeptide in
      water. Free energy surfaces in the (phi, psi) dihedral angle space,
      (3)J(H(N),H(alpha)) NMR dipolar coupling constants, basin populations, and
      peptide-water radial distribution functions (RDF) were calculated from replica
      exchange simulations and compared to both experiment and fully classical force
      field calculations using the Amber ff99SB force field. In contrast with the
      computational chemist's intuitive idea that the more expensive a method the
      better its accuracy, the ff99SB force field results were more accurate than most
      of the semiempirical methods, with the exception of RM1. None of the methods,
      however, was able to accurately reproduce the experimental data. Analysis of the
      results indicate that the specific QM/MM interactions have little influence on
      the sampling of free energy surfaces, and the differences are well explained
      simply by the intrinsic properties of the various QM methods.

PMID- 19848432
TI  - Lipocarbazoles, secondary metabolites from Tsukamurella pseudospumae Acta 1857
      with antioxidative activity.
AB  - A family of new secondary metabolites with a carbazole moiety and an alkyl side
      chain was isolated from Tsukamurella pseudospumae strain Acta 1857. They were
      named lipocarbazoles in accordance with their chemical structures, which were
      determined by mass spectrometry and NMR spectroscopy. Lipocarbazoles are free
      radical scavengers showing antioxidative activity.

PMID- 19848433
TI  - Norselic acids A-E, highly oxidized anti-infective steroids that deter mesograzer
      predation, from the Antarctic sponge Crella sp.
AB  - Five new steroids, norselic acids A-E (1-5), were isolated from the sponge Crella
      sp. collected in Antarctica. The planar structures of the norselic acids were
      established by extensive NMR spectroscopy and mass spectrometry studies, and the
      configuration of norselic acid A (1) was elucidated by X-ray crystallography.
      Norselic acid A displays antibiotic activity against methicillin-resistant
      Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), vancomycin
      resistant Enterococcus faecium (VRE), and Candida albicans and reduces
      consumption of food pellets by sympatric mesograzers. Compounds 1-5 are also
      active against the Leishmania parasite at low micromolar levels.

PMID- 19848434
TI  - Using enzyme assays to evaluate the structure and bioactivity of sponge-derived
      meroterpenes.
AB  - Enzyme screening of crude sponge extracts prioritized a 2005 Papua New Guinea
      collection of Hyrtios sp. for further study. The MeOH extract contained
      puupehenone and four puupehenone analogues (1, 2, 3, 5, and 7) along with a new
      diastereomer, 20-epi-hydroxyhaterumadienone (4), and a new analogue, 15-oxo
      puupehenoic acid (6). The drimane terpene core of 4 and 6 was rapidly
      dereplicated, and the modified Mosher's method identified 4, while 1D and 2D NMR
      techniques were used to solve 6. These compounds plus noteworthy repository
      natural products and standards were tested against three lipoxygenase isozymes,
      human 5-, 12-, and 15-lipoxygenases. Significant potency and selectivity profiles
      were exhibited in the human 5-lipoxygenase assay by puupehenone (1) and
      jaspaquinol (9) and structural factors responsible for activity identified.

PMID- 19848435
TI  - Fernene triterpenoids from the lichen Pyxine berteriana.
AB  - Two new fernene triterpenoids, fern-9(11)-en-3,19-dione (1) and 3beta-acetoxyfern
      9(11)-en-19-one (2), together with the known 3beta-acetoxyfern-9(11)-en-19beta-ol
      (3) and lichexanthone (4), have been isolated from the acetone extract of the
      lichen Pyxine berteriana. The structures of the new compounds were established on
      the basis of IR, extensive 1D and 2D NMR, and MS analyses. Although several fern
      9(11)-enes have been isolated from lichens, compounds 1 and 2 are the first
      examples of naturally occurring fernene triterpenoids with a carbonyl function at
      C-19.

PMID- 19848436
TI  - Revised structure of the alkaloid drymaritin.
AB  - In 2004, a new anti-HIV alkaloid named drymaritin was isolated from Drymaria
      diandra. The authors identified the alkaloid as 5-methoxycanthin-4-one on the
      basis of spectroscopic data. Here we describe a synthetic approach that
      unambiguously gave 5-methoxycanthin-4-one, but the synthetic product showed
      spectroscopic data significantly different from those of the Drymaria alkaloid.
      Extensive re-evaluation of the spectroscopic data published for this and related
      alkaloids has led to the conclusion that drymaritin does not have a canthin-4-one
      backbone, but is identical to the known alkaloid cordatanine (4-methoxycanthin-6
      one).

PMID- 19848437
TI  - Cerebrolysin: a review of its use in dementia.
AB  - Cerebrolysin is a parenterally administered, porcine brain-derived peptide
      preparation that has pharmacodynamic properties similar to those of endogenous
      neurotrophic factors. In several randomized, double-blind trials of up to 28
      weeks' duration in patients with Alzheimer's disease, Cerebrolysin was superior
      to placebo in improving global outcome measures and cognitive ability. A large,
      randomized comparison of Cerebrolysin, donepezil or combination therapy showed
      beneficial effects on global measures and cognition for all three treatment
      groups compared with baseline. Although not as extensively studied in patients
      with vascular dementia, Cerebrolysin has also shown beneficial effects on global
      measures and cognition in this patient population. Cerebrolysin was generally
      well tolerated in clinical trials, with dizziness (or vertigo) being the most
      frequently reported adverse event. Although further studies with Cerebrolysin,
      including longer term trials and further exploration of its use in combination
      with cholinesterase inhibitors, are needed to more clearly determine its place in
      the management of Alzheimer's disease and vascular dementia, available data
      suggest that Cerebrolysin is a useful addition to the treatment options available
      for dementia.

PMID- 19848438
TI  - Lipid-lowering therapy for the primary prevention of cardiovascular disease in
      the elderly: opportunities and challenges.
AB  - Although HMG-CoA reductase inhibitors (statins) have been shown to reduce the
      risk of cardiovascular events in patients aged 65-80 years who have clinical
      cardiovascular disease, fewer data are available for elderly patients without
      cardiovascular disease. Treatment guidelines recommend a low-density lipoprotein
      cholesterol goal of <100 mg/dL for those with cardiovascular disease or diabetes
      mellitus but vary in their recommendations for primary prevention. Moderate-dose
      statins have been shown to be effective and safe in properly selected elderly
      patients up to the age of 80 years. High-dose statins have also been shown to be
      effective and reasonably safe in patients without significant co-morbidities up
      to the age of 75 years. With advancing age, the potential for benefit from
      cholesterol-lowering treatment needs to be weighed against the increasing risk of
      muscle and hepatic toxicity, as well as competing causes of morbidity and
      mortality.

PMID- 19848440
TI  - Medication-related admissions in older people: a cross-sectional, observational
      study.
AB  - BACKGROUND: Medication-related admissions are an important cause of hospital
      admissions in older people. The scope for prevention is less clear. OBJECTIVES:
      To characterize medication-related hospital admissions in older people and assess
      their preventability. METHODS: This was a cross-sectional, observational study
      conducted over 3 months. A pharmacist based in the medical admissions ward of a
      north London hospital screened all patients aged > or =65 years. A specialist
      physician assembled additional information, which was presented to a multi
      professional panel to confirm attribution and preventability. A total of 409
      patients were screened, of whom 14% (95% CI 10.6, 17.4) had medication-related
      problems, 6.4% (95% CI 4.0, 8.8) were admitted because of medication-related
      problems and 3.9% (95% CI 2.0, 5.8) were considered to have preventable
      medication-related problems. Medicines to prevent or treat cardiovascular disease
      were implicated in 69% (18/26) of the medication-related admissions and 69%
      (11/16) of preventable medication-related admissions. Amongst hospitalized
      patients, admission attributed to adverse drug reaction was more likely as the
      number of medications being taken increased, and admission attributed to
      undertreatment was more likely as the number of pre-existing conditions
      increased. CONCLUSION: Medication-related admissions are common in older people
      and over half are preventable. Morbidity associated with medicines used for
      cardiovascular disease is important. There is a difficult balance to be struck
      between avoiding iatrogenic illness in older people and ensuring they benefit
      from medications for pre-existing conditions. Opportunities exist for improving
      the delivery of care to reduce adverse outcomes.

PMID- 19848441
TI  - Effects of potent anticholinergics, sedatives and antipsychotics on postoperative
      mortality in elderly patients with hip fracture: a retrospective, population
      based study.
AB  - BACKGROUND: Concomitant use of several medications for somatic and mental
      disorders is common in elderly people and increases the risk of falls, with hip
      fracture being the most serious consequence. OBJECTIVE: The objective of this
      study was to describe relationships between use of sedatives, antipsychotics or
      potent anticholinergics and postoperative mortality in patients with hip
      fractures. METHODS: A retrospective analysis was conducted on population-based
      data collected during a 2-year period from 1999 to 2000 on 461 hip fracture
      surgery patients aged > or = 65 years in Finland. Information on co-morbidities
      and intake of sedatives, antipsychotics and potent anticholinergics was obtained
      from the original patient records. Information on deaths was obtained from the
      official death statistics in Finland. RESULTS: In men, use of potent
      anticholinergics was associated with excess age-adjusted mortality at 30 days, 3
      months, 6 months and 3 years, but not in women at any timepoint. CONCLUSION: Use
      of potent anticholinergic drugs emerged as an independent predictor of excess
      mortality in men at 3 months and 3 years. Presence of cardiovascular disease and
      chronic lung disease were independent risk factors for excess mortality at 6
      months and 3 years in men. In addition, chronic lung disease independently
      predicted excess mortality at 30 days. Use of potent anticholinergics should be
      evaluated critically after hip fracture surgery, especially in men with
      cardiovascular or chronic lung diseases.

PMID- 19848439
TI  - Quality of life in glaucoma and three other chronic diseases: a systematic
      literature review.
AB  - Chronic diseases have a long-term negative impact on quality of life (QOL).
      Decreased QOL is associated with increased financial burden on healthcare systems
      and society. However, few publications have investigated the impact of glaucoma
      on patients' QOL in comparison with other chronic diseases observed in patients
      with similar demographic characteristics. To this end, a systematic literature
      search to assess QOL in glaucoma and three other chronic diseases (osteoporosis,
      type 2 diabetes mellitus and dementia) was performed. A total of 146 publications
      were identified that reported QOL using six commonly used generic QOL
      instruments: 36-, 12- and 20-item Short-Form Health Surveys (SF-36, -12 and -20),
      EuroQoL (EQ-5D), Sickness Impact Profile (SIP) and the Health Utilities Index
      Mark III (HUI-III). The publication breakdown was as follows: glaucoma (10%),
      osteoporosis (26%), diabetes (52%) and dementia (12%); one publication assessed
      QOL in glaucoma, diabetes and dementia. QOL was affected to a similar or slightly
      lesser degree by glaucoma than by osteoporosis, diabetes or dementia. Among the
      publications reporting SF-36, -12 and -20 evaluations, physical component scores
      were generally lower than mental component scores across all diseases. QOL was
      affected more in patients with glaucoma than in demographically matched non
      glaucomatous controls according to SF-20 assessment. EQ-5D and SIP results showed
      that QOL decreased as the severity of glaucoma increased. Patients with glaucoma
      had the lowest scores on the SIP instrument, indicating better QOL than patients
      with osteoporosis or diabetes (no data were available on dementia). The HUI-III
      instrument identified poorer QOL in patients with dementia than other diseases,
      probably due to cognitive deficits. However, for some of the instruments, data
      were scarce, and interpretation of the results should be conservative. Although
      there are limited published QOL studies in glaucoma, its impact on QOL appears to
      be broadly similar to that of other serious chronic diseases. Development of a
      QOL instrument that measures vision-specific and general health aspects would
      better document the impact of glaucoma on QOL and would facilitate comparisons
      with other chronic disease states.

PMID- 19848442
TI  - Health state values during the first year of drug treatment in early-stage
      Parkinson's disease: a prospective, population-based, cohort study.
AB  - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder in
      the elderly that may lead to both motor and non-motor symptoms with consequent
      severe impairment of quality of life. PD also represents a substantial economic
      burden on society because of the patient's decreased ability to work, increased
      need for care and need for costly treatment. Evaluation of quality-adjusted life
      years (QALYs) is an important tool in cost-effectiveness analyses. To date,
      however, few data have become available about the utility gains or losses
      associated with the disease and its management. OBJECTIVES: To evaluate the
      changes in health state values in patients with newly diagnosed PD during their
      first year of drug treatment, and to calculate the gain in QALYs and the
      incremental cost-effectiveness ratio (ICER) for this patient group. METHODS: In
      this prospective, population-based, cohort study, 199 patients with incident PD
      and 172 controls were followed over 1 year. Clinical data, drug use and utility
      scores obtained from the Short Form 6D (SF-6D) health state questionnaire were
      documented. RESULTS: Patients with PD had lower SF-6D utility scores than
      controls at baseline. Patients started on antiparkinsonian drugs had an
      improvement in mean utility scores of 0.039 from 0.667 to 0.706 (p < 0.05). The
      ICER was euros 45,259 (2007 values) per QALY, of which two-thirds consisted of
      the costs of drugs and one-third represented the costs of clinical consultations.
      CONCLUSION: Drug treatment in patients with early-stage PD increases health state
      values, but the ICER is high. Further investigations will be necessary to capture
      the full consequences of treatment of PD and to evaluate the efficacy of disease
      management in this setting.

PMID- 19848443
TI  - Prevalence and correlates of high body mass index in rural Appalachian children
      aged 6-11 years.
AB  - INTRODUCTION: In rural regions of the United States of America, estimates of
      pediatric obesity often exceed national averages. This problem may be
      particularly pronounced in Appalachian regions, where significant health and
      economic disparities abound. This study presents the findings of a body mass
      index (BMI) screening program for 6-11 year old children living in a rural
      Appalachian community. County-wide estimates of high BMI (>or=85th percentile)
      were obtained to understand the health status and needs of our pediatric
      community and to compare obesity prevalence rates with national averages. An
      additional aim was to identify subpopulations of children who may warrant
      clinical intervention due to demographic and behavioral risks factors of high
      BMI. METHODS: A school-based BMI screening was conducted of 6-11 year old
      children in southeastern Ohio. Investigators collected 3 sets of height and
      weight measurements from approximately 2000 elementary school students between
      2006 and 2007. Caregivers for a subset of this population also completed a health
      behaviors questionnaire. RESULTS: Thirty-eight percent of children had high BMI,
      with 17% at risk for overweight and 20.9% overweight. Boys were 23% more likely
      than girls to be overweight (chi(2)(1) = 95% CI = 1.08, 1.40) and 11% more likely
      to become overweight with each year of age (OR = 1.11, 95% CI = 1.07, 1.15).
      Overweight children were more likely to view television, eat meals at school, and
      live with a caregiver who smokes. CONCLUSIONS: Consistent with expectations,
      prevalence of high BMI in this sample of rural Appalachian children exceeds
      national averages. Prevalence of overweight varied by age and sex; boys are
      particularly vulnerable to developing obesity, especially as they age.
      Preliminary survey data suggest that eating breakfast at home and at school and
      increased hours of television viewing may be associated with higher BMI,
      especially in younger boys.

PMID- 19848444
TI  - Pro-oxidant effect of vitamin C coadministration with bisphenol A, nonylphenol,
      and octylphenol on the reproductive tract of male rats.
AB  - This study was performed to investigate whether bisphenol A (BPA), nonylphenol
      (NP), and octylphenol (OP) induce oxidative stress on the reproductive tract of
      male rats and if coadministration of vitamin C can prevent any possible oxidative
      stress. Wistar male rats were divided into seven groups as control (vehicle;
      olive oil), BPA, NP, OP, BPA+C, NP+C, and OP+C. BPA, OP, and NP groups (25
      mg/kg/day) were administered orally to rats three times a week for 45 days. In
      BPA+C, NP+C, and OP+C groups, vitamin C (60 mg/kg/day) was administered orally
      along with BPA, OP, and NP (25 mg/kg/day) treatments. Malondialdehyde (MDA)
      appeared at significantly higher concentrations in BPA-, NP-, and OP-treated
      groups, when compared to control group. No significant decrease was observed in
      testes MDA levels of vitamin C coadministrated groups, compared with BPA, NP, and
      OP treatment groups. Decreased levels of reduced glutathione (GSH) were found in
      testes of BPA-, NP-, OP-treated rats. No significant increase was observed in
      testes GSH levels of BPA+C, NP+C, and OP+C groups, compared with BPA, NP, and OP
      treatment groups. Histological examination showed that vitamin C coadministrated
      groups had much more congestion areas, atrophy, and germinal cell debris in
      testes than those observed in other groups. Abnormal sperm percentages of BPA,
      BPA+C, NP+C, and OP+C groups were increased. In conclusion, the present results
      demonstrated that BPA, NP, and OP generate reactive oxygen species that cause
      oxidative damage in testes of rats. Coadministration of vitamin C aggravates this
      damage.

PMID- 19848445
TI  - Concentration-dependent differing actions of the nonsteroidal anti-inflammatory
      drug, celecoxib, in distearoyl phosphatidylcholine multilamellar vesicles.
AB  - The interactions of the nonsteroidal anti-inflammatory drug, celecoxib, with 1,2
      distearoyl-sn-glycero-3-phosphocholine multilamellar vesicles were studied as a
      function of temperature and different drug concentrations, using Fourier
      transform infrared spectroscopy, differential scanning calorimetry, and turbidity
      technique at 440 nm. Our studies reveal that celecoxib lowers the main phase
      transition temperature and decreases the fluidity of the membranes at all
      concentrations. Celecoxib induced opposing effects on molecular order at
      different concentrations by increasing the ordering of the system at low
      concentrations and disordering it at high concentrations. Further, the drug
      increases the number of hydrogen bonds around the carbonyl groups at low
      concentrations in both phases, whereas the degree of dehydration increases at
      high concentrations in the gel phase. An evidence of phase separation has also
      been clearly observed at high concentrations. Thus, depending on the
      concentration used, celecoxib induces significant changes in the biophysical
      properties of membranes that may aid in understanding its mechanism of action.

PMID- 19848446
TI  - Preparation and characterization of medium-chain fatty acid liposomes by
      lyophilization.
AB  - In this study, medium-chain fatty acid (MCFA) liposomes were prepared by the film
      ultrasonic dispersion, modified ethanol injection, and reverse-phase evaporate
      methods. The results indicated that the liposomes prepared by the thin-film
      ultrasonic dispersion method had a high entrapment efficiency of 82.7% and a good
      distribution in size diameters. The MCFA liposomes were freeze-dried and the
      optimal preparation conditions of freeze-drying were as follows: The
      cryoprotectants were mannitol and sucrose (1:1 w/w), the hydrated medium was
      distilled water, and the freeze-drying time was 48 hours. Under these conditions,
      the freeze-dried MCFA liposomes had a perfect appearance, a small particle size,
      and high encapsulation efficiency. The mean diameters were 251.1 and 265.3 nm,
      and the encapsulation efficiencies were 80.5 and 79.2% for freshly prepared and
      reconstituted liposomes, respectively.

PMID- 19848447
TI  - Effect of altered temperature storage on the in vitro cellular uptake of liposome
      drug products.
AB  - The aim of this study was to evaluate whether temperature stress conditions
      affect the cellular uptake of liposomal doxorubicin, Doxil (DXL; Ortho Biotech,
      Raritan, New Jersey, USA), and liposomal daunorubicin, DaunoXome (DXM; Gilead
      Sciences, San Dimas, California, USA). Uptake of these cytotoxic compounds is
      essential for their pharmacological effect. Commercially available DXL and DXM
      were stressed for 6 days under altered temperature conditions of 22 and 50
      degrees C, as compared to storage in their buffered formulations at the labeled
      temperature of 4 degrees C. The cellular uptake of the liposomal drugs was
      measured by fluorescence intensity in human ovarian SKOV-3 and murine macrophage
      J774A.1 cell lines following a 4-hour exposure to DXL or DXM. There was a 5- to
      10-fold increase in the cellular uptake of DXL and DXM in both cell lines after
      stress exposure to 50 degrees C. Exposure of DXL to 22 degrees C stress decreased
      its uptake by SKOV-3 cells, when compared to exposure of DXL to 4 degrees C
      control conditions. A cell-based uptake assay may provide a means to assess
      changes in the functional activity of liposomes in conjunction with evaluation of
      their physicochemical properties in order to evaluate the stability and integrity
      of liposomes.

PMID- 19848448
TI  - Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8
      agonists.
AB  - Toll-like receptor (TLR)-mediated signaling is proposed as an immunotherapeutic
      target against tumorigenesis. Natural killer (NK) cells play a critical role in
      host defense against tumors. Specifically, formation of tumor metastasis in
      various organs can be suppressed by the local activity of NK cells. In this
      study, we present a novel TLR7 agonist (termed SC-1) that induces pro
      inflammatory cytokines in human blood cells, activates NK cell function, and is
      highly efficient in preventing lung metastases in a pulmonary metastatic Renca
      model. Furthermore, a second compound (termed SC-2), acting as dual-specific TLR7
      and TLR8 agonist, was evaluated with respect to its immunostimulatory and NK cell
      activating capacities. The release of pro-inflammatory cytokines was shown to be
      even more pronounced with this compound. Additional experiments showed a
      significant up-regulation of activation marker CD69 on NK cells and increased
      cytolytic activity of peripheral blood cells compared to the effect of a
      monospecific TLR7 agonist SC-1. Normally, TLR7 and TLR8 are expressed on
      different immune cell subpopulations. TLR7 expression on antigen-presenting cells
      is detected in plasmacytoid dendritic cells, CD34+-derived dendritic cells, and B
      cells, whereas TLR8 is mainly expressed on cells of the myeloid lineage, such as
      monocytes, macrophages, and myeloid dendritic cells. Therefore, a compound that
      activates both TLR7 and TLR8 would result in a highly efficient immune system
      activation and may give rise to an enhanced anti-tumor activity in vivo compared
      to that elicited by a monospecific TLR7 agonist.

PMID- 19848449
TI  - Diffusional properties of zein membranes and matrices.
AB  - INTRODUCTION: Zein is a hydrophobic corn protein, rich in leucine, proline, and
      alanine, that has been investigated as an excipient in pharmaceutical
      formulations, maybe used as a biodegradable/biocompatible material for controlled
      release formulations. Zein's swelling behaviors under different conditions (e.g.,
      pH, ionic strength, and permeant's charge) were investigated in a previous study
      and it showed that swelling indeed influenced zein's permeation. METHODS: The
      diffusional behavior of model drugs through or from zein systems was
      investigated. Diffusional parameters such as effective diffusion coefficients,
      porosities, and tortuosities were calculated from release and membrane diffusion
      profiles for zein matrices and membranes. In addition, an alternative method of
      calculating porosity and tortuosity was proposed. RESULTS: The diffusional
      properties of zein systems appear to be primarily through aqueous channels that
      form during hydration and swelling in aqueous media. Permeation and release
      results show that the amount of diffused or released drug depends on permeant
      solubility and matrix/membrane permeability parameters (i.e., porosity and
      tortuosity). DISCUSSION: Calculated diffusional parameters for zein matrices and
      membranes support the aqueous channel model. CONCLUSIONS: Zein membranes and
      matrices hydrate and swell to form aqueous channels that are the dominant
      diffusional pathways.

PMID- 19848450
TI  - Abstracts of the 9th World Congress of Perinatal Medicine. October 24-28, 2009.
      Berlin, Germany.

PMID- 19848543
TI  - "....Macavity's not there!".

PMID- 19848544
TI  - Disinformation on both sides of the Atlantic: a patient's view.

PMID- 19848545
TI  - Changes in regional cerebral blood flow and glucose metabolism following
      electroacupuncture at LI 4 and LI 11 in normal volunteers.
AB  - OBJECTIVES: Although numerous trials have demonstrated the clinical effects of
      acupuncture, the mechanism of its therapeutic effect still remains uncertain.
      Recent neuroimaging studies using functional magnetic resonance imaging, single
      photon emission computed tomography (SPECT), and positron emission tomography
      (PET) have revealed that acupuncture therapy may alter brain activity. This study
      was performed to evaluate changes in regional cerebral blood flow and glucose
      metabolism following electroacupuncture (EA) in normal volunteers. DESIGN AND
      SETTING: Twenty (20) normal volunteers were enrolled for brain SPECT and 13
      normal volunteers were enrolled for (18)F-fluorodeoxyglucose PET. A few days
      after the baseline measurements, EA was performed at two acupoints (LI 4 and LI
      11) for 15 minutes and a second brain image was acquired for each subject. We
      used statistical parametric mapping 2 to analyze the changes in brain perfusion
      and glucose metabolism. RESULTS: Significant increases in perfusion were observed
      in the left middle frontal gyrus, the superior parietal gyrus, the right superior
      frontal gyrus, and the middle parietal gyrus. Following EA, glucose metabolism
      significantly increased in the left superior medial frontal gyrus, the middle
      frontal gyrus, and the right superior medial frontal gyrus (paired t-test,
      uncorrected p < 0.005). CONCLUSIONS: There were specific increases in both
      regional cerebral blood flow and glucose metabolism following EA in both frontal
      regions. This common brain response in localized regions was induced from
      stimulation of specific acupoints (LI 4 and LI 11).

PMID- 19848546
TI  - Randomized controlled trial of mindfulness-based therapy for dyspnea in chronic
      obstructive lung disease.
AB  - OBJECTIVES: Patients with chronic obstructive lung disease (COPD) suffer from
      significant dyspnea and may benefit from complementary and alternative medicine
      (CAM) therapies aimed at mitigating symptoms. The objective of this study was to
      test the efficacy of a mindfulness-based breathing therapy (MBBT) on improving
      symptoms and health-related quality of life in those with COPD. DESIGN: We
      conducted a randomized controlled trial of 8-week mindfulness-based breathing
      therapy (MBBT) compared to support groups to test efficacy on improving symptoms
      and health-related quality of life in those with COPD. SETTING: The setting for
      this study was an academic-affiliated veterans healthcare system. SUBJECTS: The
      subjects consisted of 86 patients with COPD. INTERVENTIONS: MBBT included weekly
      meetings practicing mindfulness mediation and relaxation response. OUTCOME
      MEASURES: The main outcome measure was a post 6-minute-walk test (6MWT) Borg
      dyspnea assessment. Other outcome measures included health-related quality of
      life measures, 6MWT distance, symptom scores, exacerbation rates, and measures of
      stress and mindfulness. Analysis of covariance compared differences in outcomes
      between groups; paired t test evaluated changes within groups. RESULTS:
      Participants were predominantly elderly men with moderate to severe COPD. We
      found no improvements in dyspnea (post 6MWT Borg difference between the MBBT and
      support group was 0.3 (95% confidence interval [CI]: -1.1, 1.7). We found no
      differences between groups in almost all other outcome measures by either
      intention-to-treat analysis or within the subset that completed assigned group
      sessions. For the physical summary scale of the generic Short Form-36 for
      Veterans, the difference between outcomes favored the support group (4.3, 95% CI:
      0.4, 8.1). Participant retention was low compared to mind-body trials that
      randomize from CAM wait lists. CONCLUSIONS: This trial found no measurable
      improvements in patients with COPD receiving a mindfulness-based breathing CAM
      therapy compared to a support group, suggesting that this intervention is
      unlikely to be an important therapeutic option for those with moderate-to-severe
      COPD.

PMID- 19848547
TI  - Does random participant assignment cause fewer benefits in research participants?
      Systematic review of partially randomized acupuncture trials.
AB  - OBJECTIVES: It has been suggested that the random assignment of participants does
      not cause harm to patients in clinical trials. However, in a recent study,
      patient preference affected the health outcome of the patients. It can therefore
      be assumed that patients who are allocated at random may be affected by placebo
      effects that are associated with the treatment of their choice. The aim of this
      study was to determine whether random participant assignment in acupuncture
      trials causes fewer benefits to the participants. DATA SOURCES: The following
      computerized databases were searched from their inception to December 2008:
      MEDLINE, SCOPUS, CINAHL, Cochrane Registered Trial, British Library Direct, and
      Google Scholar. REVIEW METHODS: This was a systematic review of partially
      randomized acupuncture trials with adequate randomization generation and
      concealment of participant group allocation as well as large enough sample sizes
      to satisfy a power calculation. RESULTS: Six (6) trials that met the selection
      criteria were included. The randomized acupuncture group comprised patients with
      different demographics and health outcomes than the observational group.
      Substantial numbers of eligible patients refused to participate in the
      randomization. The baseline patient characteristics were different between the
      randomized acupuncture group and the observational group. The proportion of
      patients who dropped out of or withdrew from the study was also different between
      the groups, with significantly more dropping out from the observational group
      than the randomized group. Patients in the observational group had significantly
      better health outcomes than patients in the randomized group, with a standardized
      mean difference of 0.06 (95% confidence interval 0.03-0.09). CONCLUSIONS: We
      found that patients who were randomly assigned to treatment groups in acupuncture
      trials had fewer health benefits than those who were nonrandomly assigned.

PMID- 19848548
TI  - Attitudes about the use of complementary and alternative medicine in cancer
      treatment.
AB  - OBJECTIVES: The aim of this study was to achieve an understanding what determines
      the attitude of people toward complementary and alternative medicine (CAM) is
      essential in decisions about costly therapies in cancer treatment. DESIGN: This
      study involved population-based surveys conducted in 1995 and 2005. SETTING: In
      1995 and 2005, a quota sample of 2400 Austrians ages > or =15 was selected and
      invited in writing to participate in a survey to study beliefs and attitudes
      about cancer, its risk factors, and treatment. The sample comprised 0.04% of the
      population > or =15 years of age and was representative in terms of age, sex,
      occupational status, and area of residence. SUBJECTS: The subjects included 4073
      Austrian adults (2073 participants enrolled in the 1995 survey and 2000
      participants of the 2005 survey). INTERVENTION: Respondents were visited in their
      homes by trained interviewers. The interview was face-to-face, using a
      standardized questionnaire. OUTCOME MEASURES: We used a dichotomized variable as
      the outcome, placing high value on CAM (rated as 1 or 2 on a 5-level Likert
      scale) versus everything else (rated 3-5). RESULTS: Positive personal experiences
      with people cured of cancer improved the likelihood of a positive perception of
      CAM (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.17-1.59 for those who
      reported knowing someone who was cured of cancer, compared to those who did not).
      In multivariate models adjusting for personal attitude toward mainstream
      medicine, subjects with more formal education were also more likely to believe
      that CAM is valuable (OR, 1.28; 95% CI, 1.02-1.61), as were women (OR, 1.40; 95%
      CI, 1.20-1.64) and people ages 70 and above (OR, 1.46; 95% CI, 1.02-2.08). A
      higher appreciation of mainstream medicine was inversely associated with the
      value placed on CAM in cancer therapy (OR, 0.43; 95% CI, 0.22-0.85). CONCLUSIONS:
      In this, to our knowledge, the first study to evaluate predictors of CAM
      preference in cancer treatment in a national probability sample, we found more
      formal education, female gender, and older age to be the strongest predictors of
      a person favoring CAM therapy in cancer treatment. Our data also suggest that
      people who are satisfied with conventional care were less inclined to value CAM,
      whereas a positive personal experience with cancer cures improved positive
      perception of CAM.

PMID- 19848549
TI  - CAM, free speech, and the British legal system: overstepping the mark?
AB  - The British Chiropractic Association recently won a libel case against the
      science writer and CAM 'skeptic' Dr Simon Singh for publishing an article in a
      British newspaper in which he accused them of promoting 'bogus' treatments. This
      has ignited a campaign in the UK to 'keep the libel laws out of science'. In this
      article, the tension between media freedom of expression and defamation law is
      examined, and possible ramifications for CAM in the UK explored.

PMID- 19848550
TI  - The campaign against CAM and the notion of "evidence-based".
AB  - Since quite some time, at least in the United Kingdom, a campaign against
      complementary and alternative medicine (CAM) treatments and training courses has
      been happening. Given some prominence in the media, this campaign seems to aim at
      having CAM courses scrutinized, CAM treatments taken off reimbursement schemes,
      and brandishing doctors and academics dealing with CAM as quacks. The buzzword
      used is "evidence-based," with the presupposition that, while conventional
      medicine is "evidence-based," CAM is not. It is worthwhile to examine the notion
      of "evidence" used in this discussion. I argue that it is a rather unwholesome
      type of evidence that is referred to here, namely only the difference between an
      active treatment and a sham treatment. For several reasons this is too restricted
      and not sound, as it creates several paradoxes, for instance the efficacy
      paradox. This consists in what is now empirically documented, whereas a CAM
      placebo can be actually more effective than a conventional, supposedly evidence
      based, treatment. This shows that the discussion is really about something
      completely different: CAM has become a real player in the health services field,
      threatening revenues of the pharmaceutical industry. Taken together with a series
      of events this suggests that this campaign is carefully staged. It requires that
      we take the question of what "evidence" means to the heart of the methodological
      discussion, also for the sake of a broader, more wholesome notion of what counts
      as evidence. It also requires that we keep producing good data with a broad
      enough outlook comparing CAM treatments with conventional ones, and not just with
      placebo.

PMID- 19848552
TI  - Cationic vesicles from novel bolaamphiphilic compounds.
AB  - Effective targeted drug delivery by cationic liposomes is difficult to achieve
      because of their rapid clearance from the blood circulation. Bolaamphiphiles that
      form monolayer membrane may provide vesicles with improved stability, as shown
      for archaeosomes. We investigated a series of bolaamphiphiles with acetylcholine
      head groups and systematic structural changes in their hydrophobic domain for
      their ability to form stable nanovesicles. Bolaamphiphiles with two aliphatic
      chains separated by a short amide midsection produced spherical nanovesicles
      ranging in diameter from 80 to 120 nm. These vesicles lost their encapsulated
      material within 24 hours of incubation in phosphate-buffered saline (PBS).
      Similar bolaamphiphiles with a longer midsection produced a mixture of fibers and
      more stable nanovesicles. Bolaamphiphiles with ester amide midsection produced
      only spherical nanovesicles that were stable during incubation in PBS for several
      days. Vesicles made from bolaamphiphiles with acetylcholine head groups
      conjugated to the aliphatic chain via the amine were less stable than vesicles
      made from bolaamphiphiles with head groups conjugated to the aliphatic chain via
      the acetyl group. Vesicles that were stable in vitro showed good stability in the
      blood circulation after intravenous administration to mice. These results help in
      elucidating the bolaamphiphile structures needed to form stable cationic vesicles
      for targeted drug delivery.

PMID- 19848553
TI  - A 1-year toxicity study in dogs is no longer a scientifically justifiable core
      data requirement for the safety assessment of pesticides.
AB  - A review of publications on pesticides assessing the need for 1-year toxicity
      studies in dogs was performed. Four key peer-reviewed papers with different
      approaches investigated the value of a 1-year dog study in addition to a 3-month
      study. Despite different databases and approaches, each concluded with the
      recommendation to limit the testing of pesticides in dogs to a duration of 3
      months. The combined weight of evidence presented in this review reinforces these
      independent conclusions. Therefore, the routine inclusion of a 1-year dog study
      as a mandated regulatory requirement for the safety assessment of pesticides is
      no longer justifiable and a globally harmonized approach should be taken to match
      the latest legislation of the European Union and the US EPA.

PMID- 19848554
TI  - Fine-tuning of POPC liposomal leakage by the use of beta-cyclodextrin and several
      hydrophobic guests.
AB  - The effect of entrapped beta-cyclodextrin (beta-CD) on the stability of
      multilamellar vesicles (MLVs) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (POPC), prepared by the dehydration-rehydration method, was studied by monitoring
      the release of 5(6)-carboxyfluorescein encapsulated into the liposomes. Different
      hydrophobic guests, such as Fullerene C(60), have been incorporated into the POPC
      bilayer in order to modify the membrane composition. The kinetic results as well
      as ESI-MS measurements evidenced that the destabilizing activity of beta-CD is
      due to the formation of beta-CD inclusion complexes and the consequent removal of
      selected bilayer constituents from the liposomal membrane. Hence, when beta-CD
      was added to the liposomes in the form of a strong, water-soluble 2:1 beta
      CD/C(60) inclusion complex, such a destabilizing effect was not observed.
      However, the same beta-CD/C(60) inclusion complex does not form as a result of
      C(60) extraction from the bilayer. This may be attributed either to the
      overwhelming concentration of POPC with respect to C(60) and/or to the fact that
      C(60) is largely aggregated in the bilayer. Turbidimetric and fluorimetric
      determinations of lamellarity and entrapped volume of the studied MLVs provided
      further evidence of the alteration of the liposomal bilayer as a consequence of
      the addition of beta-CD and/or the presence of the studied guests.

PMID- 19848555
TI  - Comparative effects of continuous combined hormone therapy and tibolone on body
      composition in postmenopausal women.
AB  - OBJECTIVE: To compare the effects of tibolone with those of continuous combined
      hormone replacement therapy (HT) on body composition in postmenopausal women.
      METHODS: One hundred and fifty postmenopausal women were enrolled in a
      randomized, controlled trial to compare the effects of tibolone with continuous
      combined HT on body composition. Patients were randomly allocated into three
      groups and followed for 9 months. Of the subjects included, 50 women received 2.5
      mg tibolone plus one Cal+D tablet (500 mg calcium and 200 IU vitamin D) daily, 50
      women received 0.625 mg conjugated equine estrogen and 2.5 mg medroxyprogesterone
      acetate (CEE/MPA) plus one Cal+D tablet daily, and the rest (50 women) received
      only one Cal+D tablet and served as a control group. Body composition was
      evaluated with measurements of body mass index (BMI), weight, waist-to-hip ratio
      (WHR), fat mass and fat-free mass (FFM) before and after the intervention.
      Measurements of body fat mass percentage, fat mass, body fat-free mass percentage
      and fat-free mass (FFM) were assessed by measurement of skin-fold thickness.
      RESULTS: Tibolone significantly increased weight, BMI and FFM and decreased WHR
      after the treatment in comparison with baseline (p < 0.05). However, only weight
      and BMI increased significantly in the CEE/MPA group after the treatment (p <
      0.05). There were significant increases in weight, BMI and fat mass in the
      control group after 9 months. In the comparison of the parameters after the
      treatment between the three groups, tibolone significantly increased FFM compared
      with the control and CEE/MPA groups (p < 0.01). CONCLUSIONS: The effect of
      tibolone on body composition is favorable and therefore tibolone may be regarded
      as an alternative to continuous combined hormone therapy in postmenopausal women.

PMID- 19848556
TI  - Ecological opportunity in adaptive radiation of Galapagos endemic land snails.
AB  - The classic evolutionary hypothesis of ecological opportunity proposes that both
      heterogeneity of resources and freedom from enemies promote phenotypic divergence
      as a response to increased niche availability. Although phenotypic divergence and
      speciation have often been inferred to be the primary consequences of the release
      from competition or predation that accompanies a shift to a new adaptive zone,
      increased phenotypic variation within species is expected to represent the first
      stage resulting from such a shift. Using measures of intraspecific morphological
      variation of 30 species of Galapagos endemic land snails in a phylogenetically
      controlled framework, we show that the number of local congeners and the number
      of local plant species are associated with lower and higher intraspecific
      phenotypic variation, respectively. In this clade, ecological opportunity thus
      explicitly links the role of competition from congeners and the heterogeneity of
      resources to the extent of intraspecific phenotypic divergence as adaptive
      radiation proceeds.

PMID- 19848557
TI  - Multiple sclerosis: prevalence and factors impacting bladder and bowel function
      in an Australian community cohort.
AB  - PURPOSE: To describe the prevalence and impact of bladder and bowel dysfunction
      on quality of life (QoL) in persons with multiple sclerosis (pwMS) in an
      Australian community cohort and to explore the relationships between commonly
      used continence measures. METHODS: Patients (N = 73) recruited from a tertiary
      hospital database, interviewed using standardised measures, based on the
      framework of International Classification of Functioning, Disability and Health.
      RESULTS: Of 73 participants (mean age 50 yrs, 73% female, 56% progressive MS),
      two thirds were bothered by urinary frequency whereas half reported urinary
      incontinence, and 14% bowel incontinence. Urinary problems impacted emotional
      health (31%), ability to perform household chores (22%) and physical recreation
      (28%), with detrimental impact on QoL. There was a significant relationship
      between symptoms, level of urogenital distress (rho = 0.74, p < 0.001) and impact
      of incontinence (rho = 0.68, p < 0.001). The single item of Urological
      Association Symptom Index assessing impact of bladder symptoms on QoL correlated
      significantly with all other bladder scales (rho = 0.60-0.74), making it a
      potential 'screening tool' to identify patients for further assessment.
      CONCLUSION: Continence issues cause significant disability in pwMS. Improved
      awareness of currently available treatment options and clinically robust trials
      are needed to assess outcomes of continence intervention.

PMID- 19848558
TI  - Physiological cost of walking in those with chronic fatigue syndrome (CFS): a
      case-control study.
AB  - PURPOSE: To examine the physiological cost of walking in subjects with chronic
      fatigue syndrome (CFS) and a matched control group, walking at their preferred
      and at matched walking speeds. METHODS: Seventeen people with CFS and 17 matched
      controls participated in this observational study of physiological cost during
      over-ground gait. Each subject walked for 5 min at their preferred walking speed
      (PWS). Controls then walked for 5 min at the same pace of their matched CFS
      subject. Gait speed and oxygen uptake, gross and net were measured and oxygen
      uptake was expressed per unit distance ambulated. CFS subjects completed the CFS
      Activities and Participation Questionnaire (CFS-APQ). RESULTS: At PWS the CFS
      group walked at a slower velocity of 0.84 +/- 0.21 m s(-1) compared to controls
      with a velocity of 1.19 +/- 0.13 m s(-1) (p < 0.001). At PWS both gross and net
      oxygen uptake of CFS subjects was significantly less than controls (p = 0.023 and
      p = 0.025 respectively). At matched-velocity both gross and net physiological
      cost of gait was greater for CFS subjects than controls (p = 0.048 and p = 0.001,
      respectively). CONCLUSION: The physiological cost of walking was significantly
      greater for people with CFS compared with healthy subjects. The reasons for these
      higher energy demands for walking in those with CFS have yet to be fully
      elucidated.

PMID- 19848559
TI  - The complex interplay between pain intensity, depression, anxiety and
      catastrophising with respect to quality of life and disability.
AB  - PURPOSE: To identify subgroups of patients with chronic pain based on the
      occurrence of depression, anxiety and catastrophising and the duration of pain
      and pain intensity. In addition to this, the relationship between the subgroups
      with respect to background variables, diagnosis, pain-related disability and
      perceived quality of life are investigated. METHODS: This study used 433 patients
      with chronic pain including 47 patients with spinal cord injury-related pain, 150
      with chronic whiplash associated disorders and 236 with fibromyalgia. The
      participants answered a postal questionnaire that provided background data, pain
      intensity and duration and psychological and health-related items. RESULTS: On
      the basis of depression, anxiety, catastrophising, pain intensity and duration,
      we identified subgroups of patients with chronic pain that differed with respect
      to perceived quality of life, disability and diagnosis. The psychological
      factors, especially depression, significantly influenced perceived quality of
      life and disability. Pain intensity and duration play a minor role with respect
      to quality of life, although pain intensity is associated to perceived
      disability. CONCLUSIONS: The results of this study highlight the importance of
      not looking at patients with chronic pain as a homogenous entity. A detailed
      assessment, including psychological factors with emphasis on depressive symptoms,
      might be essential for planning and carrying through treatment and
      rehabilitation.

PMID- 19848560
TI  - What treatment packages do UK physiotherapists use to treat postural control and
      mobility problems after stroke?
AB  - OBJECTIVE: The aim of this study was to identify the treatment packages
      (combinations of interventions) used to treat postural control and mobility
      problems for patients with stroke. METHOD: A convenience sample of 74
      physiotherapists from 34 National Health Service hospitals recorded the
      interventions used to treat postural control and mobility problems for 251
      patients with stroke in 1156 treatment sessions using the Stroke Physiotherapy
      Intervention Recording Tool (Tyson and Selley, Disabil Rehabil 2004;26:1184 -
      1188). Descriptive statistics assessed the frequency with which the interventions
      were used and geometric coding identified treatment packages. RESULTS: The most
      frequently used interventions involved facilitation, practice of activities and
      their components and mobilisations. The least frequently used interventions
      involved the provision of equipment, teaching carers or professionals and
      exercise. Two treatment packages were identified; one involving the facilitation
      (of activities and their components) and the other involving whole activities
      (facilitation and practice). CONCLUSIONS: Interventions are often combined in two
      treatment packages to treat postural control and mobility problems after stroke.
      One involved facilitation (of whole and component activities) and the other
      involved practice and facilitation of whole activities. Future research in which
      conventional or standard UK stroke physiotherapy is delivered should focus on
      these interventions and exclude atypically used interventions.

PMID- 19848561
TI  - Drug release from lipid liquid crystalline phases: relation with phase behavior.
AB  - INTRODUCTION: We studied the release of propranolol hydrochloride (PHCl), a water
      soluble amphiphilic drug, from monoolein (MO)/water and phytantriol/water
      systems. METHODS: We related the dissolution profiles with phase behavior and
      viscosity of the different liquid crystalline phases. Diolein has been added
      aiming to stabilize the cubic phases and thus preventing formation of less
      viscous (lamellar) phases. RESULTS: Formulations display first-order release
      rates and diffusion release mechanism. Some formulations (mostly MO) were close
      to zero-order release in the first 120 minutes. DISCUSSION: Release mechanism can
      be influenced by phase changes during dissolution. CONCLUSIONS: Both MO and
      phytantriol show good potential to be used for propranolol hydrochloride
      sustained drug release.

PMID- 19848562
TI  - "The strength of weak ties" revisited: achieving true integration of disease
      management and lifestyle management.

PMID- 19848563
TI  - Impact of decision support in electronic medical records on lipid management in
      primary care.
AB  - Electronic decision-support tools may help to improve management of
      hyperlipidemia and other chronic diseases. This study examined the impact of
      lipid management tools integrated into an electronic medical record (EMR) in
      primary care practices. This randomized controlled trial was conducted in a
      national network of physicians who use an outpatient EMR. Adult primary care
      physicians were randomized by office to receive an electronic form that was
      embedded in the EMR. The form contained prompts regarding suboptimal care based
      on Adult Treatment Panel-III (ATP-III) guidelines, as well as reporting tools to
      identify patients outside of office visits whose lipid management was suboptimal.
      All active patients, ages 20-79 years, whose physicians participated in the
      study, were categorized as high, moderate, or low cardiovascular risk, and the
      proportion who were tested for hyperlipidemia, at lipid goal, and on lipid
      lowering medications if not at goal were measured according to ATP-III
      guidelines. A total of 105 physicians from 25 offices and 64,150 patients were
      included in the study. Outcomes improved for most measures from before to 1 year
      after the intervention (November 1, 2005 to October 31, 2006). However, after
      controlling for confounding variables and for clustering in multilevel modeling,
      only up-to-date lipid testing for high-risk patients was statistically better in
      the intervention group as compared to the control group (adjusted odds ratio
      15.0, P < 0.05). This study showed few differences in quality of lipid management
      after implementing an EMR-based disease management intervention in primary care
      settings. Future studies may need to examine more comprehensive interventions
      that include office staff in a team approach to care.

PMID- 19848564
TI  - Initial implementation of a depression care manager model: an observational study
      of outpatient utilization in primary care clinics.
AB  - Many primary care physicians understand the challenges of taking care of patients
      with depression. Care management models for depression have been described as
      more effective than usual practice. The implementation of such a model requires a
      clinic manager to be able to predict how this new process might impact staffing
      and clinical demand. This study was designed to evaluate the initial impact of
      the implementation of a depression care manager (CM) model on the utilization of
      outpatient visits. The hypothesis is that the introduction of a CM model for
      depression in a primary care practice would be associated with an increased
      utilization of health care resources when compared to usual care (UC). There were
      38 patients enrolled during the initial 2 months of implementation of the CM
      model. Using a retrospective medical record review, the CM population was
      compared to a similar group receiving UC (N = 49), and a significant increase in
      the percentage of patients who were seen for any reason in the CM population was
      found (65.8% vs. 36.7%, P = 0.01). The average CM patient had 1.24 outpatient
      visits for any reason vs. 0.69 for the UC group (P = 0.01). When specifically
      focusing on outpatient visits for depression, the CM group averaged 0.95 visits
      per patient as compared to the UC patients having 0.55 visits per patient (P =
      0.04). This study suggests that the initial implementation of a CM model for
      treatment of depression will increase outpatient utilization. .

PMID- 19848565
TI  - Convenient care clinics: the future of accessible health care--the formation
      years 2006-2008.
AB  - In the 2 years since the Convenient Care Association (CCA), a nonprofit
      organization representing the members of the Convenient Care industry, was
      founded, this new model has gained significant traction in the health care
      marketplace and in the awareness of health care consumers. When the CCA was
      formed, fewer than 200 clinics were in operation. Now, there are more than 1000
      clinics seeing patients, and more than 3.5 million patient visits have been
      recorded across the country. As the industry has expanded, some challenges have
      arisen, mostly in the form of legislative and regulatory initiatives aimed at
      impeding clinic operation. The CCA and its members continue to undertake
      substantial efforts to build comprehensive quality processes into the convenient
      care model. The effect of these measures has been to mitigate the allegations of
      poor quality and inconsistent care that have been levied against the clinics. The
      media and public responses have been generally positive, and policy makers and
      other decision makers have been receptive to the benefits convenient care can
      offer to their constituents.

PMID- 19848566
TI  - Incorporating tailored interactive patient solutions using interactive voice
      response technology to improve statin adherence: results of a randomized clinical
      trial in a managed care setting.
AB  - The current study presents the impact of a behavior change program to increase
      statin adherence using interactive voice response (IVR) technology. Subjects were
      affiliated with a large health benefit company, were prescribed a statin (index)
      and had no lipid-lowering pharmacy claims in the previous 6 months, and were
      continuously enrolled in the plan for 12 months prior and 6 months post index
      statin. Potential subjects (1219) were contacted by the IVR system; 497 gave
      informed consent. Subjects were asked to respond to 15 questions from the IVR
      that were guided by several behavior change theories. At the conclusion of the
      questions, subjects were randomly assigned to either a control group (n = 244),
      who received generic feedback at the conclusion of the call and were then mailed
      a generic cholesterol guide, or an experimental group (n = 253), who received
      tailored feedback based on their cholesterol-related knowledge, attitudes,
      beliefs, and perceived barriers to medication adherence, and were mailed a
      tailored guide that reinforced similar themes. Subjects in the experimental group
      had the opportunity to participate in 2 additional tailored IVR support calls.
      The primary dependent variable was 6-month point prevalence, defined as claims
      evidence of a statin on days 121-180 post index statin. Subjects in the
      experimental group had a significantly higher 6-month point prevalence than the
      controls (70.4% vs. 60.7%, P < 0.05). Results of this study suggest that a
      behavioral support program using IVR technology can be a cost-effective modality
      to address the important public health problem of patient nonadherence with
      statin medication.

PMID- 19848567
TI  - Obesity and expenditures among elderly Veterans Health Administration users with
      diabetes.
AB  - A retrospective cross-sectional analysis of Veterans Health Administration (VHA)
      administrative and Medicare fee-for-service (FFS) claims data was used to
      evaluate the association between body mass index (BMI) categories and
      expenditures among elderly VHA users with diabetes. The study sample included
      respondents to the 1999 Large Health Survey of Veteran Enrollees who were
      diagnosed with diabetes in fiscal year 1999, age 65 or older, and enrolled in
      Medicare FFS (N = 79,934). Types of expenditures included inpatient, outpatient,
      and a summation of the 2 in the fiscal year 1999. VHA expenditures were from the
      Health Economics Resource Center Average Cost Database and Medicare expenditures
      were the paid amounts recorded in the claims. BMI was grouped into 4 exclusive
      categories: normal (18.5-24.9), overweight (25-29.9), obese (30-34.9), and
      morbidly obese (> or =35). Generalized linear models with the log-link function
      were used to examine the association between BMI categories and expenditures,
      controlling for sociodemographic factors, diabetes duration, health status, and
      health behavior. Almost half of the study sample was overweight (47.6%), followed
      by obese (22.6%), normal (20.7%), and morbidly obese (9.1%). Patients with normal
      BMI had the highest average total expenditures ($10,470) followed by overweight
      ($7526). Total expenditure was not significantly different between obese and
      morbidly obese BMI groups ($6597 vs. $6772). After controlling for all other
      variables, normal weight patients with diabetes had greater total, inpatient, and
      outpatient expenditures. The study showed that elderly diabetes patients with
      normal weight incur much higher costs than obese or morbidly obese patients.
      Further research is needed to examine the causes of high cost among normal weight
      patients with diabetes to better understand resource needs and to improve
      resource allocations.

PMID- 19848568
TI  - Quality measurement in diabetes care.
AB  - This study aimed to evaluate diabetes quality measurement efforts, assess their
      strengths and areas for improvement, and identify gaps not adequately addressed
      by these measures. We conducted an environmental scan of diabetes quality
      measures, focusing on metrics included in the National Quality Measures
      Clearinghouse or promulgated by leading measurement organizations. Key informant
      interviews were also completed with thought leaders who develop, promote, and use
      quality measures. The environmental scan identified 146 distinct measures
      spanning 31 clinical processes or outcomes. This suggests a measurement system
      that is both redundant and inconsistent, with many different measures assessing
      the same clinical indicators. Interviewees believe that current diabetes
      measurement efforts are excessively broad and complex and expressed a need for
      better harmonization of these measures. Several gaps were also found, including a
      lack of measures focusing on population health, structural elements of health
      care, and prevention of diabetes.

PMID- 19848569
TI  - Determining business models for financial sustainability in regional health
      information organizations (RHIOs): a review.
AB  - Regional health information organizations (RHIOs) have the potential to alleviate
      today's health care problems by granting providers access to a supported body of
      clinical information for all patients in a given region. While the promise of and
      enthusiasm for RHIOs is immense, the issue of their financial sustainability
      remains unclear. It has been said that the business model supporting a regional
      or national health information network is as essential, if not more essential,
      than the technology that makes it feasible. Currently, there is a clear lack of
      concrete business models implemented in RHIOs' projects. This article reports the
      results of a literature review of the current status of the adaptation and
      implementation of business models by RHIOs for successful financial
      sustainability. Based on the review, this article also attempts to evaluate the
      existing financial situation of RHIOs to determine and recommend the best models
      of economic sustainability. Significant findings include RHIOs' present financial
      environment, planning, and self-sustainability methods. Future studies will be
      needed as RHIOs continue to grow and move toward the implementation phase of
      their development.

PMID- 19848571
TI  - CGM--a technology in evolution.

PMID- 19848572
TI  - Multiple stressors and the response of vascular endothelial cells: the effect of
      aging and diabetes.
AB  - BACKGROUND: The present study examined the effects of local heat, global heat,
      and the interaction between these two endothelial stressors on the blood flow of
      the skin of the foot in people who are older and who have diabetes. METHODS:
      Subjects who were older (mean age 64.2 +/- 5.9 years) and were younger (mean age
      25.7 +/- 2.9 years) and subjects who had diabetes (mean age 62 +/- 5.9 years,
      mean duration 13.2 +/- 9.1 years) participated. Subjects were exposed to three
      global temperatures (16 degrees C, 24 degrees C, and 32 degrees C), and the blood
      flow response was recorded on the foot with a laser Doppler flow meter for 30 s
      following applications of local heat (30 degrees C, 33.5 degrees C, and 37
      degrees C) using a Peltier junction to clamp the skin for 2 min. RESULTS: All
      three groups significantly increased blood flow from the 16-24 degrees C
      environments for the 37 degrees C application of local heat (P(Younger) = 0.02,
      P(Older) = 0.02, P(Diabetes) = 0.01). Those with diabetes and those who were
      older only increased blood flow 5% and 6% from the 24-32 degrees C environment,
      which was not statistically significant (P(Older) = 0.12, P(Diabetes) = 0.14).
      CONCLUSIONS: There appears to be considerable blood flow reserve in younger
      subjects to tolerate heat stress. In contrast, older subjects and those with
      diabetes reach a critical level after which additional heat does not cause in
      increase in blood flow.

PMID- 19848573
TI  - Patient perceptions of injection pain and anxiety: a comparison of NovoFine 32
      gauge tip 6mm and Micro Fine Plus 31-gauge 5mm needles.
AB  - BACKGROUND: Injecting insulin may cause pain and anxiety and lead to suboptimal
      treatment of diabetes mellitus. The aim of this randomized, open-label, crossover
      study was to compare two types of needle design and diameter in patients with
      diabetes injecting insulin. METHODS: Patients with diabetes injecting insulin
      twice daily for at least 3 months were included. A NovoFine (Novo Nordisk,
      Bagsverd, Denmark) 32-gauge tip 6mm tapered needle and a Micro Fine Plus (Nippon
      Becton Dickinson Co. Ltd., Tokyo, Japan) 31-gauge 5mm standard needle were
      compared. Patients were randomized to use one needle for 1 week, followed by the
      alternative needle for another week. Before and after each week patients
      completed a 14-item questionnaire assessing overall satisfaction and usability of
      the needles. Each item was scored on a visual analog scale from -100 (worst) to
      +100 (best). RESULTS: Thirty patients (24 men, six women) took part in this
      study: 24 with type 2 diabetes and six with latent autoimmune diabetes in adults.
      The mean +/- SD for age was 57.8 +/- 7.6 years, for body mass index was 23.0 +/-
      3.1 kg/m(2), for duration of diabetes was 15.6 +/- 9.8 years, and for mean
      glycated hemoglobin was 7.1 +/- 1.1%. Patients were more satisfied with the use
      of NovoFine 32-gauge tip 6mm needles (P < 0.0001), found the needles less
      frightening (P < 0.05) and less painful (P < 0.01), and caused less frequent
      bleeding and bruising (P < 0.001) than Micro Fine Plus 31-gauge 5mm needles.
      CONCLUSIONS: These results suggest that the diameter and design of the needle
      play an important role in reducing injection pain and needle anxiety, which is
      particularly important for insulin initiation.

PMID- 19848574
TI  - Time-action profile and patient assessment of inhaled insulin via the Exubera
      device in comparison with subcutaneously injected insulin aspart via the FlexPen
      device.
AB  - BACKGROUND: The goal of our investigation was to compare the
      pharmacokinetics/pharmacodynamics properties of and patient preference for
      insulin aspart applied with the FlexPen (Novo Nordisk, Bagsvaerd, Denmark) (IAFP)
      with pulmonary human insulin applied with the Exubera (Pfizer, New York, NY)
      device (HIEX). METHODS: Twelve patients with diabetes (six with type 1 and six
      with type 2; eight men, four women; age, 54.5 +/- 11.0 years; duration of
      diabetes, 16.5 +/- 10.6 years; hemoglobin A1c, 7.5 +/- 0.7%; body mass index,
      29.5 +/- 7.2 kg/m(2); mean +/- SD) participated in an open-label, randomized,
      euglycemic clamp study. The patients received 11 units of IAFP or a dose
      equivalent of (3 + 1 mg) insulin from HIEX in a randomized sequence on two
      different study days. Insulin plasma levels and the required glucose infusion
      rate (GIR) were monitored for a time period of 6 h. In addition, the patients'
      individual ratings from 1 (excellent) to 5 (poor) regarding several different
      handling items were assessed using a questionnaire. RESULTS: No significant
      difference in the pharmacokinetics/pharmacodynamics parameters could be observed
      between IAFP and HIEX within the first 120 min. In the second part of the clamp
      procedure, plasma insulin levels (area under the curve versus time [AUC]) and the
      GIR was significantly higher after HIEX compared with IAFP (insulin AUC(120-360),
      66,232 +/- 4,521 vs. 48,852 +/- 2,999 pmol/L, P < 0.05; GIR AUC(120-360), 8,928
      +/- 1,334 vs. 6,805 +/- 1,655 mg/kg/min). A superior patient judgment was
      obtained for the FlexPen with regard to trust in insulin delivery (2.3 +/- 1.1
      vs. 2.8 +/- 1.0), trust in correct insulin dosing (1.8 +/- 1.1 vs. 2.6 +/- 0.9),
      size (2.3 +/- 1.1 vs. 3.6 +/- 0.9), and appearance of the device (2.4 +/- 1.0 vs.
      3.8 +/- 0.9) (P < 0.05, respectively). CONCLUSIONS: Insulin treatment with HIEX
      was found to have pharmacokinetics/pharmacodynamics properties comparable to
      IAFP. Both insulin administration technologies were overall evaluated positive,
      but most patients preferred IAFP.

PMID- 19848575
TI  - Preventing hypoglycemia using predictive alarm algorithms and insulin pump
      suspension.
AB  - BACKGROUND: Nocturnal hypoglycemia is a significant problem. From 50% to 75% of
      hypoglycemia seizures occur at night. Despite the development of real-time
      glucose sensors (real-time continuous glucose monitor [CGM]) with hypoglycemic
      alarms, many patients sleep through these alarms. The goal of this pilot study
      was to assess the feasibility using a real-time CGM to discontinue insulin pump
      therapy when hypoglycemia was predicted. METHODS: Twenty-two subjects with type 1
      diabetes had two daytime admissions to a clinical research center. On the first
      admission their basal insulin was increased until their blood glucose level was
      <60 mg/dL. On the second admission hypoglycemic prediction algorithms were tested
      to determine if hypoglycemia was prevented by a 90-min pump shutoff and to
      determine if the pump shutoff resulted in rebound hyperglycemia. RESULTS: Using a
      statistical prediction algorithm with an 80 mg/dL threshold and a 30-min
      projection horizon, hypoglycemia was prevented 60% of the time. Using a linear
      prediction algorithm with an 80 mg/dL threshold and a 45-min prediction horizon,
      hypoglycemia was prevented 80% of the time. There was no rebound hyperglycemia
      following pump suspension. CONCLUSIONS: Further development of algorithms is
      needed to prevent all episodes of hypoglycemia from occurring.

PMID- 19848576
TI  - Computerized Automated Reminder Diabetes System (CARDS): e-mail and SMS cell
      phone text messaging reminders to support diabetes management.
AB  - BACKGROUND: Cell phone text messaging, via the Short Messaging Service (SMS),
      offers the promise of a highly portable, well-accepted, and inexpensive modality
      for engaging youth and young adults in the management of their diabetes. This
      pilot and feasibility study compared two-way SMS cell phone messaging with e-mail
      reminders that were directed at encouraging blood glucose (BG) monitoring.
      METHODS: Forty insulin-treated adolescents and young adults with diabetes were
      randomized to receive electronic reminders to check their BG levels via cell
      phone text messaging or e-mail reminders for a 3-month pilot study. Electronic
      messages were automatically generated, and participant replies with BG results
      were processed by the locally developed Computerized Automated Reminder Diabetes
      System (CARDS). Participants set their schedule for reminders on the secure CARDS
      website where they could also enter and review BG data. RESULTS: Of the 40
      participants, 22 were randomized to receive cell phone text message reminders and
      18 to receive e-mail reminders; 18 in the cell phone group and 11 in the e-mail
      group used the system. Compared to the e-mail group, users in the cell phone
      group received more reminders (180.4 vs. 106.6 per user) and responded with BG
      results significantly more often (30.0 vs. 6.9 per user, P = 0.04). During the
      first month cell phone users submitted twice as many BGs as e-mail users (27.2
      vs. 13.8 per user); by month 3, usage waned. CONCLUSIONS: Cell phone text
      messaging to promote BG monitoring is a viable and acceptable option in
      adolescents and young adults with diabetes. However, maintaining interest levels
      for prolonged intervals remains a challenge.

PMID- 19848577
TI  - Dual radiotracer analysis of cholinergic neuronal changes in prediabetic mouse
      pancreas.
AB  - BACKGROUND: Pancreatic neuronal changes associated with beta cell loss in type 1
      diabetes mellitus are complex, involving, in part, parasympathetic mechanisms to
      compensate for preclinical hyperglycemia. The parasympathetic neurotransmitter
      acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet
      beta cells. The vesicular ACh transporter (VAChT) receptor has been shown to be a
      useful marker of cholinergic activity in vivo. The positron emission tomography
      (PET) radiotracer (+)-4-[(18)F]fluorobenzyltrozamicol ([(18)F]FBT) binds to the
      VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET.
      The compound 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), available in a
      tritiated form, binds to M3 muscarinic receptors on beta cells and is a potential
      target for assessing pancreatic beta cell mass. In this study, we investigate the
      feasibility of dual radiotracer analysis in identifying neurofunctional changes
      that may signify type 1 diabetes mellitus in its early preclinical state.
      METHODS: Ex vivo determinations of pancreatic uptake were performed in
      prediabetic nonobese diabetic mice and controls after intravenous injection of
      [(18)F]FBT or 4-[(3)H]DAMP. Beta cell loss in prediabetic mice was confirmed
      using immunohistochemical methods. RESULTS: [(18)F]FBT uptake was significantly
      higher in prediabetic pancreata than controls: 3.22 +/- 0.81 and 2.51 +/- 1.04,
      respectively (P < 0.03). 4-[(3)H]DAMP uptake was significantly lower in
      prediabetic pancreata than controls: 0.612 +/- 0.161 and 0.968 +/- 0.364,
      respectively (P = 0.01). CONCLUSIONS: These data suggest that a combination of
      radiotracer imaging agents that bind to neuronal elements intimately involved in
      insulin production may be an effective method of evaluating changes associated
      with early beta cell loss using PET.

PMID- 19848578
TI  - The use of an Energy Monitor in the management of diabetes: a pilot study.
AB  - BACKGROUND: This study evaluated the use of an accelerometer-based device in
      helping to manage blood glucose levels (BGLs) in people with diabetes mellitus.
      METHODS: Five people with diabetes were given a triaxial accelerometer-based
      device (Energy Monitor) that measured energy levels associated with activities of
      daily living. For 3 months, they were required to wear the device and to continue
      with their usual diabetes therapy. The body mass index (BMI) and glycosylated
      hemoglobin (HbA(1c)) were recorded to assess any potential improvement in blood
      glucose control. The relationship between BGL and measured energy level was also
      investigated. RESULTS: Overall, there was a significant reduction of HbA(1c) from
      7.48 +/- 1.21% to 6.98 +/- 1.44% (P < 0.05). There was no significant change in
      BMI. It was also found that higher energy levels resulted in much lower
      fluctuations in BGL change between meals compared to low energy levels. Moreover,
      the weekly mean activity score showed an increase in activity levels from the
      second week to the final week. CONCLUSIONS: This pilot study demonstrated that
      the Energy Monitor could improve the management of diabetes by allowing people
      with diabetes to view and manage daily physical activity in addition to their
      usual diabetes therapy.

PMID- 19848579
TI  - Dose-response characteristics of high-viscosity hydroxypropylmethylcellulose in
      subjects at risk for the development of type 2 diabetes mellitus.
AB  - BACKGROUND: Hydroxypropylmethylcellulose (HPMC) is a modified cellulose fiber
      that creates a viscous solution in the gastrointestinal tract. The present study
      examined the dose-response characteristics of high-viscosity (HV)-HPMC
      consumption on postprandial glucose and insulin levels in men and women at
      increased risk for type 2 diabetes mellitus. METHODS: Subjects were a subset of
      participants in two trials with elevated peak postprandial glucose [>or=7.8
      mmol/L (>or=140 mg/dL)] and body mass index (BMI) >or=27 kg/m(2). Subjects (n =
      39) consumed breakfast meals containing 75 g of carbohydrate, each of which
      contained 1, 2, 4, or 8 g of HV-HPMC or a cellulose control in a randomized,
      double-blind manner. Each subject completed tests with control and two HV-HPMC
      doses. RESULTS: Peak glucose concentration was lower than control (all P < 0.01)
      following 2 g (10%), 4 g (18%), and 8 g (20%) of HV-HPMC. Peak insulin was also
      reduced (P < 0.01) following 2 g (32%), 4 g (35%), and 8 g (46%) of HV-HPMC doses
      versus control. Incremental areas for glucose from 0 to 120 min were reduced by 8
      40% versus control but only reached significance for the 4-g and 8-g conditions,
      whereas incremental areas under the insulin curves were reduced by 14-53% (P <
      0.01 for 2, 4, and 8 g of HV-HPMC). CONCLUSIONS: Among subjects at risk for type
      2 diabetes mellitus, 1.0-8.0 g of HV-HPMC blunted postprandial glucose and
      insulin responses in a dose-dependent manner. Additional research is warranted to
      assess whether chronic consumption might retard the development or progression of
      glucose intolerance.

PMID- 19848580
TI  - Comment on Owens and Bolli.

PMID- 19848582
TI  - Relationship of p53 overexpression on cancers and recognition by anti-p53 T cell
      receptor-transduced T cells.
AB  - Tumor suppressor p53 is reported to be an attractive immunotherapy target because
      it is mutated in approximately half of human cancers, resulting in inactivation
      and often an accumulation of the protein in the tumor cells. Only low amounts of
      protein are detectable in normal tissues. The differential display of antigen in
      normal versus tumor tissues has been reported to create an opportunity to target
      p53 by immunotherapy. We sought to determine the relationship between p53
      expression and its recognition by cognate T cells in human tumors including
      common epithelial malignancies. Inasmuch as nonsense or missense p53 mutations
      may disrupt processing and presentation, we studied tumors with either identified
      wild-type or mutated p53, based on our gene-sequencing studies or published data.
      T cells transduced with a high-affinity, p53(264-272)-reactive T cell receptor
      (TCR) derived from HLA-A2.1 transgenic mice recognized a wide panel of human
      tumor lines. There was no significant correlation between p53 expression in
      tumors and recognition by the anti-p53 TCR-transduced T cells. This conclusion
      was based on the study of 48 cell lines and is in contrast to several prior
      studies that used only a limited number of selected cell lines. A panel of normal
      cells was evaluated for recognition, and some of these populations were capable
      of stimulating anti-p53 T cells, albeit at low levels. These studies raise doubts
      concerning the suitability of targeting p53 in the immunotherapy of cancer
      patients.

PMID- 19848583
TI  - A negatively acting bifunctional RNA increases survival motor neuron both in
      vitro and in vivo.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder
      and is the leading genetic cause of infant mortality. SMA is caused by the loss
      of survival motor neuron-1 (SMN1). In humans, a nearly identical copy gene is
      present called SMN2, but this gene cannot compensate for the loss of SMN1 because
      of a single silent nucleotide difference in SMN2 exon 7. This single-nucleotide
      difference attenuates an exonic splice enhancer, resulting in the production of
      an alternatively spliced isoform lacking exon 7, which is essential for protein
      function. SMN2, however, is a critical disease modifier and is an outstanding
      target for therapeutic intervention because all SMA patients retain SMN2 and SMN2
      maintains the same coding sequence as SMN1. Therefore, compounds or molecules
      that increase SMN2 exon 7 inclusion hold great promise for SMA therapeutics.
      Bifunctional RNAs have been previously used to increase SMN protein levels and
      derive their name from the presence of two domains: an antisense RNA sequence
      specific to the target RNA and an untethered RNA segment that serves as a binding
      platform for splicing factors. This study was designed to develop negatively
      acting bifunctional RNAs that recruit hnRNPA1 to exon 8 and block the general
      splicing machinery from the exon 8. By blocking the downstream splice site, this
      could competitively favor the inclusion of SMN exon 7 and therefore increase full
      length SMN production. Here we identify a bifunctional RNA that stimulated full
      length SMN expression in a variety of cell-based assays including SMA patient
      fibroblasts. Importantly, this molecule was also able to induce SMN expression in
      a previously described mouse model of SMA and demonstrates a novel therapeutic
      approach for SMA as well as a variety of diseases caused by a defect in splicing.

PMID- 19848584
TI  - Efficient inhibition of hepatitis B virus replication in vivo, using polyethylene
      glycol-modified adenovirus vectors.
AB  - Achieving safe delivery of anti-hepatitis B virus (HBV) RNA interference (RNAi)
      effectors is an important objective of this gene-silencing technology.
      Adenoviruses (Ads) have a natural tropism for the liver after systemic
      administration, and are useful for delivery of expressed anti-HBV RNAi sequences.
      However, a drawback of Ad vectors is diminished efficacy and toxicity that
      results from stimulation of innate and adaptive immunity. To attenuate these
      effects we used monomethoxy polyethylene glycol-succinimidyl propionate (mPEG
      SPA) to modify first-generation vectors that express an anti-HBV RNAi effector.
      Efficient hepatocyte transduction and knockdown of HBV replication were achieved
      after intravenous administration of 5 x 10(9) PEGylated or native recombinant Ads
      to HBV transgenic mice. After the first injection, circulating HBV viral particle
      equivalents (VPEs) remained low for 3 weeks and began to increase after 5 weeks.
      A second dose of PEGylated anti-HBV Ad caused a less sustained decrease in
      circulating VPEs, but no silencing after a second dose was observed in animals
      treated with unmodified vector. Release of inflammatory cytokines, including
      monocyte chemoattractant protein-1 (MCP-1), interferon-gamma, interleukin-6, and
      tumor necrosis factor-alpha, was elevated in animals receiving unmodified
      vectors. However, only a modest increase in MCP-1 was observed in mice that
      received a second dose of PEG Ads. Also, polymer-conjugated vectors induced a
      weaker adaptive immune response and were less hepatotoxic than their unmodified
      counterparts. Collectively, these observations show that PEG modification of Ads
      expressing RNAi effectors improves their potential for therapeutic application
      against HBV infection.

PMID- 19848586
TI  - Effect of antimalarial drugs on Plasmodium falciparum gametocytes.
AB  - Gametocytes are the sexual stage of the malaria parasite and are essential for
      transmission to the mosquito. Antimalarial drugs have been reported to affect
      gametocyte production in vivo, which leads to a potential increase in
      transmission. We used transgenic Plasmodium falciparum parasites expressing a
      green fluorescent protein tag in a fluorescence-activated cell sorting-based
      assay to measure the effect of 8 antimalarial drugs on gametocyte production in
      vitro. Exposure to antimalarial drugs resulted in an increase in the number of
      gametocytes in test cultures. Although a dose-dependent reduction in late-stage
      gametocyte viability was observed, none of the drugs tested statistically
      significantly reduced gametocyte numbers.

PMID- 19848587
TI  - Streptococcus suis enolase functions as a protective antigen displayed on the
      bacterial cell surface.
AB  - BACKGROUND: Streptococcus suis serotype 2 (SS2) has evolved into a highly
      infectious entity, posing a great threat to public health. Screening for and
      identification of protective antigens plays an important role in developing
      therapies against SS2 infections. METHODS: Multiple strategies were used to
      investigate a new surface protein that has the potential to be a protective
      antigen. These strategies included molecular cloning, biochemical and biophysical
      analyses, enzymatic assay, immunological approaches (eg, immunoelectron
      microscopy), and experimental infections of animals. RESULTS: We identified an
      enolase gene from SS2 and systematically characterized its protein product,
      enolase. Biophysical data indicated that S. suis enolase is an octameric protein.
      Enzymatic assays verified its ability to catalyze the dehydration of 2-phospho-D
      glycerate to phosphoenolpyruvate. In consideration of the strong antigenicity of
      enolase, an efficient enolase-based method was established for monitoring SS2
      infections. Combined evidence strongly indicated that SS2 enolase can localize on
      the bacterial cell surface and facilitate bacterial adherence. Additionally, we
      found that enolase can confer complete protection against SS2 infection to mice,
      which suggests that enolase has potential as a vaccine candidate. CONCLUSIONS: We
      conclude that S. suis enolase functions as a protective antigen displayed on the
      bacterial cell surface and that it can be used to develop new strategies to
      combat SS2 infections.

PMID- 19848589
TI  - Progress in the commercial-scale production of adeno-associated viral vectors.

PMID- 19848588
TI  - Submicroscopic infection in Plasmodium falciparum-endemic populations: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Light microscopy examination of blood slides is the main method of
      detecting malaria infection; however, it has limited sensitivity. Low-density
      infections are most likely to be missed, but they contribute to the infectious
      reservoir. Quantifying these submicroscopic infections is therefore key to
      understanding transmission dynamics and successfully reducing parasite
      transmission. METHODS: We conducted a systematic review of endemic population
      surveys in which P. falciparum prevalence had been measured by both microscopy
      and a more-sensitive polymerase chain reaction (PCR)-based technique. The
      combined microscopy:PCR prevalence ratio was estimated by random-effects meta
      analysis, and the effect of covariates was determined by meta-regression.
      RESULTS: Seventy-two pairs of prevalence measurements were included in the study.
      The prevalence of infection measured by microscopy was, on average, 50.8% (95%
      confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte
      specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%
      26.6%) of the prevalence measured by PCR. A significantly higher percentage of
      total infections was detected by microscopy in areas of high, compared with low,
      transmission (74.5% when the prevalence determined by PCR was >75% versus 12.0%
      when the prevalence determined by PCR was <10%). DISCUSSION: Microscopy can miss
      a substantial proportion of P. falciparum infections in surveys of endemic
      populations, especially in areas with low transmission of infection. The extent
      of the submicroscopic reservoir needs to be taken into account for effective
      surveillance and control.

PMID- 19848592
TI  - Manufacturing recombinant adeno-associated viral vectors from producer cell
      clones.
AB  - A commercial rAAV manufacturing process needs to provide a safe product at high
      yield, be easily scalable, regulatory-compliant, and have reasonable cost of
      goods. Considerations for process development include not only product quantity
      and quality, but also ease of obtaining equipment, performing validation, and
      demonstrating control. In these regards, it is usually efficient to make use of
      proven technologies for more established areas of manufacturing, such as cell
      culture and purification methods used by the recombinant protein/monoclonal
      antibody industry. We have focused on stable mammalian producer cell lines with
      adenovirus type 5 helper virus as a means of achieving these goals. This review
      describes our current approach for generating producer cell clones and designing
      a scalable, regulatory-compliant vector production and purification process that
      addresses any product safety concerns relating to helper virus. To date, a
      producer cell line-based manufacturing process has been implemented at the 250
      liter production scale, with no foreseeable impediments to scaling up to
      commercial vector manufacturing in 2000-liter bioreactors or larger.

PMID- 19848596
TI  - Cancer gene therapy: present and future.

PMID- 19848595
TI  - Isolation and characterization of murine multipotent lung stem cells.
AB  - The capacity of the lung to repair itself after injury is well known, but the
      cell types involved in lung regeneration remain undefined. The aim of this study
      was to isolate and characterize resident progenitor/stem cells from adult mouse
      lung. We report the isolation and characterization of resident stem cells that
      have a Sca1+/CD45(-)/CD31(-) phenotype. Their immunophenotype and differentiative
      potentiality were distinct from that of other previously described lung stem
      cells. These cells underwent extensive self-renewal in culture and could
      differentiate into endothelial and lung epithelial (alveolar type I, II, and
      Clara) cells in vitro. They have exhibited some mesenchymal but no neural
      differentiation ability. Transfer of these cells into mouse models of lung injury
      significantly improved survival and minimized lung destruction. These cells may
      provide useful tools for the study of lung stem cells and the assessment of new
      therapeutic approaches for lung diseases.

PMID- 19848597
TI  - Gene-based adjuvants: a new meaning.

PMID- 19848599
TI  - High prevalence of anorectal chlamydial infection in HIV-infected men who have
      sex with men in Switzerland.
AB  - Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) were
      enrolled in an anorectal Chlamydia trachomatis screening study. Anorectal
      Chlamydia DNA was detected in 16 (10.9%) of 147 men, mainly among asymptomatic
      patients and patients having >20 sexual partners. These results support routine
      anorectal Chlamydia screening in HIV-infected MSM who report unprotected anal
      intercourse.

PMID- 19848601
TI  - Measurement of influenza vaccination coverage among healthcare personnel in US
      hospitals.
AB  - OBJECTIVE: To characterize practices related to measuring influenza vaccination
      rates among healthcare personnel in US hospitals. DESIGN: Descriptive survey.
      SETTING: Nonfederal, short-stay hospitals that provide general medical and
      surgical services, identified by use of the 2004 American Hospital Association
      Annual Survey Database. PARTICIPANTS: Healthcare personnel from 996 randomly
      sampled US hospitals stratified by region and bed size. METHODS: A self
      administered questionnaire was distributed in 2006 to infection control
      coordinators to gather data on policies and practices related to the provision of
      the influenza vaccine and on the measurement and reporting of influenza
      vaccination rates. Descriptive statistics and associations were calculated, and
      logistic regression was conducted. RESULTS: The response rate was 56% (ie, 555 of
      996 US hospitals responded to the questionnaire). Weighting accounted for
      sampling design and nonresponse. Most hospitals provided the influenza vaccine to
      employees (100%), credentialed medical staff (ie, independent practitioners;
      94%), volunteers (86%), and contract staff (83%); provision for students and
      residents was less frequent (58%). Only 69% of hospitals measured vaccination
      rates (mean coverage rate, 55%). Most hospitals that measured coverage included
      employees (98%) in the vaccination rates, whereas contract staff (53%),
      credentialed medical staff (56%), volunteers (56%), and students and residents
      (30%) were less commonly included. Among hospitals measuring coverage, 44%
      included persons for which vaccine was contraindicated, and 51% included persons
      who refused vaccination. After adjustment for region and size, hospitals with
      vaccination plans written into policy (odds ratio, 2.0 [95% confidence interval,
      1.22-7.67]) or that addressed internally reporting coverage (odds ratio, 4.8 [95%
      confidence interval, 2.97-7.66]) were more likely to measure coverage than were
      hospitals without such plans. CONCLUSIONS: Hospitals vary in terms of the groups
      of individuals included in influenza vaccination coverage measurements.
      Standardized measures may improve comparability of hospital-reported vaccination
      rates. Measuring coverage in a manner that facilitates identification of
      occupational groups with low vaccination rates may inform development of targeted
      interventions.

PMID- 19848600
TI  - Domestically acquired seoul virus causing hemorrhagic fever with renal syndrome
      Maryland, 2008.
AB  - Hantaviruses are rodent-borne viruses capable of causing human disease. The Seoul
      virus is a hantavirus that causes hemorrhagic fever with renal syndrome in East
      Asia. To our knowledge, we report the first domestically acquired case of
      hemorrhagic fever with renal syndrome caused by the Seoul virus, confirmed by
      serology testing, reverse-transcriptase polymerase chain reaction, and nucleotide
      sequence analysis. The patient presented with myalgias and fever, and developed
      acute renal failure.

PMID- 19848602
TI  - Annual incidence of latent tuberculosis infection among newly employed nurses at
      a tertiary care university hospital.
AB  - OBJECTIVE: To investigate the annual rate of tuberculosis (TB) infection among
      newly employed nurses using both tuberculin skin test (TST) and QuantiFERON-TB
      Gold (QFT-G; Cellestis Limited) assay. DESIGN: A prospective cohort study
      involving newly employed nurses. SETTING: A tertiary care university hospital in
      South Korea. METHODS: All participants (n = 196) were tested with the TST and QFT
      G assay at baseline. After 1 year, the TST and QFT-G assay were reperformed for
      subjects who had negative TST results at baseline and for all subjects,
      respectively. RESULTS: The baseline TST and QFT-G assays were positive for 101
      subjects (51.5%) and 28 subjects (14.3%), respectively; 22 subjects (11.2%) had
      positive results of both tests. Although the overall between-test agreement was
      54.9% (k = 0.151) [95% confidence interval, 0.047-0.245]), agreement improved to
      78.5% (k = 0.462 [95% confidence interval, 0.007-0.917]) for subjects who had not
      received bacille Calmette-Guerin vaccination. After 1 year, the TST yielded
      positive results for 16 (21.3%) of 75 nurses with negative baseline results, and
      the QFT-G assay yielded positive results for 21 (14.4%) of 146 subjects with
      negative baseline results. Collectively, 5 subjects (3.0%) experienced conversion
      to positive results with both tests, and 32 subjects (18.9%) experienced
      conversion to positive results with one of the tests. Neither the employing
      hospital department nor exposure to patients with TB affected test conversion
      status. CONCLUSIONS: The poor overall agreement between TST and QFT-G results may
      have been caused by the confounding effect of bacille Calmette-Guerin
      vaccination. The annual risk of TB infection among newly employed nurses was at
      least 3% on the basis of results of both the TST and QFT-G test. Stricter
      preventive strategies against TB spread should be implemented in our hospital.

PMID- 19848603
TI  - Stability and reproducibility of simultaneously detected plasma and serum
      cytokine levels in asymptomatic subjects.
AB  - Blood levels of cyto- and chemokines might reflect immune deregulations which
      might be related to lymphomagenesis. Potential utility of stored blood samples of
      a prospective cohort was evaluated by the effect of different blood sample types
      and freeze-thaw cycles on analyte levels. Bead-based immunoassays were performed
      on two fresh samples (serum, citrate and heparin plasma) of 10 asymptomatic
      adults collected 14 days apart and on aliquots of the first samples which were
      put through one to three freeze-thaw cycles to measure 11 cytokines, four
      chemokines and two adhesion molecules. Median coefficients of variation (CVs) of
      the measured analytes were 20%, 24% and 32% in serum, citrate and heparin plasma,
      respectively. Strong correlations (rank correlation coefficient 0.74-0.98) were
      observed between sample types, although small differences in analyte levels were
      observed for most analytes. Freeze-thaw cycles did not markedly change analyte
      levels. Our study supports the use of this assay among asymptomatic subjects in
      epidemiological studies.

PMID- 19848604
TI  - Epidemiology and outcomes of hospitalizations with complicated skin and skin
      structure infections: implications of healthcare-associated infection risk
      factors.
AB  - OBJECTIVE: Healthcare-associated infections are likely to be caused by drug
      resistant and possibly mixed organisms and to be treated with inappropriate
      antibiotics. Because prompt appropriate treatment is associated with better
      outcomes, we studied the epidemiology of healthcare-associated complicated skin
      and skin-structure infections (cSSSIs). PATIENTS: Persons hospitalized with cSSSI
      and a positive culture result. METHODS: We conducted a single-center
      retrospective cohort study from April 2006 through December 2007. We
      differentiated healthcare-associated from community-acquired cSSSIs by at least 1
      of the following risk factors: (1) recent hospitalization, (2) recent
      antibiotics, (3) hemodialysis, and (4) transfer from a nursing home.
      Inappropriate treatment was defined as no antimicrobial therapy with activity
      against the offending pathogen(s) within 24 hours after collection of a culture
      specimen. Mixed infections were those caused by both a gram-positive and a gram
      negative organism. RESULTS: Among 717 hospitalized patients with cSSSI, 527
      (73.5%) had healthcare-associated cSSSI. Gram-negative organisms were more common
      (relative risk, 1.24 [95% confidence interval, 1.14-1.35) and inappropriate
      treatment trended toward being more common (odds ratio, 1.29 [95% confidence
      interval, 0.85-1.95]) in healthcare-associated cSSSI than in community-acquired
      cSSSI. Mixed cSSSIs occurred in 10.6% of patients with healthcare-associated
      cSSSI and 6.3% of those with community-acquired cSSSI (P = .082) and were more
      likely to be treated inappropriately than to be nonmixed infections (odds ratio,
      2.42 [95% confidence interval, 1.43-4.10]). Both median length of hospital stay
      (6.2 vs 2.9 days; P < .001) and mortality rate (6.6% vs 1.1%; P = .003) were
      significantly higher for healthcare-associated cSSSI than community-acquired
      cSSSI. CONCLUSIONS: Healthcare-associated cSSSIs are common and are likely to be
      caused by gram-negative organisms. Mixed infections carry a >2-fold greater risk
      of inappropriate treatment. Healthcare-associated cSSSIs are associated with
      increased mortality and prolonged length of hospital stay, compared with
      community-acquired cSSSIs.

PMID- 19848605
TI  - Molecular epidemiology of invasive aspergillosis: lessons learned from an
      outbreak investigation in an Australian hematology unit.
AB  - Suspected nosocomial Aspergillus fumigatus infections in an Australian hematology
      unit were investigated by molecular typing of clinical and environmental isolates
      using polymerase chain reaction fingerprinting, CSP typing, and multilocus
      microsatellite typing. Only multilocus microsatellite typing revealed that all
      isolates were genetically distinct. The selection of an appropriate typing method
      is essential for effective outbreak investigations.

PMID- 19848606
TI  - Identification of a pseudo-outbreak of Clostridium difficile infection (CDI) and
      the effect of repeated testing, sensitivity, and specificity on perceived
      prevalence of CDI.
AB  - OBJECTIVE: To describe a pseudo-outbreak of Clostridium difficile infection (CDI)
      caused by a faulty toxin assay lot and to determine the effect of sensitivity,
      specificity, and repeated testing for C. difficile on perceived CDI burden,
      positive predictive value, and false-positive results. DESIGN: Outbreak
      investigation and criterion standard. PATIENTS: Patients hospitalized at a
      tertiary care hospital who had at least 1 toxin assay for detection of C.
      difficile performed during the period from July 1, 2004, through June 30, 2006.
      METHODS: The run control chart method and the chi(2) test were used to compare
      CDI rates and the proportion of positive test results before, during, and after
      the pseudo-outbreak. The effect of repeated testing was evaluated by using 3
      hypothetical models with a sample of 10,000 patients and various assay
      sensitivity and specificity estimates. RESULTS: In November of 2005, the CDI rate
      at the hospital increased from 1.5 to 2.6 cases per 1,000 patient-days (P < .01),
      and the proportion of positive test results increased from 13.6% to 22.1% (P <
      .01). An investigation revealed a pseudo-outbreak caused by a faulty toxin assay
      lot. A decrease of only 1.2% in the specificity of the toxin assay would result
      in a 32% increase in perceived incidence of CDI at this institution. When
      calculated by use of the manufacturer's stated specificity and sensitivity and
      this institution's testing practices, the positive predictive value of the test
      decreased from 80.6% to 4.1% for patients who received 3 tests. CONCLUSION:
      Specificity is as important as sensitivity when testing for CDI. False-positive
      CDI cases can drain hospital resources and adversely affect patients. Repeated
      testing for C. difficile should be performed with caution.

PMID- 19848607
TI  - Peripheral CXCR3-associated chemokines as biomarkers of fibrosis in chronic
      hepatitis C virus infection.
AB  - BACKGROUND: CXCR3-associated chemokines CXCL9-CXCL11 promote histologic
      progression in chronic hepatitis C virus (HCV) infection, as indicated by
      elevated intrahepatic levels of messenger RNA in patients with advanced
      inflammation and fibrosis. We evaluated the potential of peripheral chemokine
      levels to discriminate among patients with chronic HCV infection who had
      different stages of fibrosis. METHODS: Peripheral levels of CXCR3-associated
      chemokines were measured by enzyme-linked immunosorbent assay of plasma samples
      obtained from 93 patients with chronic HCV infection. Of the subjects, 79 (85%)
      were white, and 68 (73%) were infected with HCV genotype 1. RESULTS: Expression
      of all 3 chemokines, when analyzed as a group, was significantly associated with
      intrahepatic inflammation and fibrosis. Plasma levels of CXCL10 were
      significantly elevated in patients with advanced fibrosis, whereas CXCL9 levels
      were significantly elevated in patients with advanced inflammation. By
      proportional odds multivariate modeling, we observed an association between
      fibrosis and CXCL10 (P< .002) as well as between fibrosis and inflammation
      (P<.001). Of the individual parameters, the CXCL10 level was most useful in
      identifying patients with more-severe (stage 3-4) fibrosis. Discriminatory
      ability was improved by the combination of CXCL10 and CXCL9. CONCLUSIONS: The
      strong association between CXCR3-associated chemokines and fibrosis suggests that
      they may have promise as noninvasive markers of hepatic fibrosis in a
      predominantly white HCV genotype 1-infected population.

PMID- 19848608
TI  - CD4(+) T cell count decreases by ethnicity among untreated patients with HIV
      infection in South Africa and Switzerland.
AB  - BACKGROUND: Estimates of the decrease in CD4(+) cell counts in untreated patients
      with human immunodeficiency virus (HIV) infection are important for patient care
      and public health. We analyzed CD4(+) cell count decreases in the Cape Town AIDS
      Cohort and the Swiss HIV Cohort Study. METHODS: We used mixed-effects models and
      joint models that allowed for the correlation between CD4(+) cell count decreases
      and survival and stratified analyses by the initial cell count (50-199, 200-349,
      350-499, and 500-750 cells/microL). Results are presented as the mean decrease in
      CD4(+) cell count with 95% confidence intervals (CIs) during the first year after
      the initial CD4(+) cell count. RESULTS: A total of 784 South African (629
      nonwhite) and 2030 Swiss (218 nonwhite) patients with HIV infection contributed
      13,388 CD4(+) cell counts. Decreases in CD4(+) cell count were steeper in white
      patients, patients with higher initial CD4(+) cell counts, and older patients.
      Decreases ranged from a mean of 38 cells/microL (95% CI, 24-54 cells/microL) in
      nonwhite patients from the Swiss HIV Cohort Study 15-39 years of age with an
      initial CD4(+) cell count of 200-349 cells/microL to a mean of 210 cells/microL
      (95% CI, 143-268 cells/microL) in white patients in the Cape Town AIDS Cohort >
      or =40 years of age with an initial CD4(+) cell count of 500-750 cells/microL.
      CONCLUSIONS: Among both patients from Switzerland and patients from South Africa,
      CD4(+) cell count decreases were greater in white patients with HIV infection
      than they were in nonwhite patients with HIV infection.

PMID- 19848609
TI  - Human Papillomavirus (HPV) type 16 and type 18 DNA Loads at Baseline and
      Persistence of Type-Specific Infection during a 2-year follow-up.
AB  - BACKGROUND: Studies of viral load-associated persistence of human papillomavirus
      (HPV) infection are rare, with inconsistent results reported. METHODS: The study
      subjects were 741 and 289 women who were positive for HPV type 16 (HPV-16) and
      HPV type 18 (HPV-18), respectively, at the time of enrollment into in the ASCUS
      LSIL (Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous
      Intraepithelial Lesion) Triage Study and who returned 1 or more times for HPV
      testing during a biannual 2-year follow-up. The numbers of HPV-16 and HPV-18
      copies per nanogram of cellular DNA at baseline were measured by use of real-time
      polymerase chain reaction. RESULTS: Women with, compared with women without,
      persistent infection at month 6 of follow-up had a higher viral load at
      enrollment (P< .001, for HPV-16; P=.01, for HPV-18). The association of each 1
      log(10) increase in viral load with persistence of HPV-16 or HPV-18 during the
      first 6 months of the study was statistically significant among women with
      multiple HPV types at enrollment (for HPV-16: odds ratio [OR], 1.53 [95%
      confidence interval {CI}, 1.29-1.82]; for HPV-18: OR, 1.35 [95% CI, 1.09-1.68])
      but not among women with monotype infections (in tests assessing the interaction
      between viral load and coinfection, P=.002 for HPV-16 and P=.34 for HPV-18).
      Among women who continued to have positive results at month 6, 12, or 18,
      persistence of infection for another 6 months was unassociated with the viral
      load at baseline. CONCLUSION: Prevalent infection with a higher viral load of HPV
      16 or HPV-18 was associated with short- but not long-term persistence.

PMID- 19848610
TI  - No rebound of morbidity following intermittent preventive sulfadoxine
      pyrimethamine treatment of malaria in infants in Gabon.
AB  - In the context of a trial studying intermittent preventive sulfadoxine
      pyrimethamine treatment of malaria in infants in Lambarene, Gabon, children aged
      18-30 months were followed up after having received their last dose at an age of
      15 months. In the intention-to-treat population, the protective efficacy against
      all malaria episodes was -18.0 (95% confidence interval, -97.4 to 29.5; P =
      .529). The protective efficacy against first or only anemia episode was -45.3
      (95% confidence interval, -234.5 to 36.3; P=.375). The protective efficacies were
      negative and were not statistically significant. These results do not appear to
      support the concept of a rebound effect after intermittent preventive sulfadoxine
      pyrimethamine treatment of malaria in infants. Clinical trials registration.
      NCT00167843.

PMID- 19848611
TI  - Impact of crystalline form changing on behavior of microcapsules prepared from
      three-component gel system.
AB  - In this paper, the effect of anhydrous-monohydrate process-induced transformation
      of theophylline was examined in microcapsules produced by in situ gelation method
      using sodium alginate, hydroxypropylmethylcellulose and hydroxyethylcellulose.
      Films produced from gel were applied to characterize the changes by NIR
      spectroscopy, X-ray, DSC method and stereomicroscopy because it is easier to
      study that in films in the case of gel systems used in situ gelation process. The
      properties of end-product are influenced by the swelling ability, equilibrium
      water uptake, release profile and encapsulation efficiency. Water penetration and
      drug release were evaluated by Davidson-Peppas and Korsmeyer-Peppas models. The
      ex tempore formed monohydrate crystals were smaller and built into the matrix
      structure in a greater extent. Increased drug release, matrix erosion and diffuse
      reflectance values at 1470 and 1950 nm were observed added theophylline later
      into the gel because of developing a denser structure.

PMID- 19848612
TI  - Inductive heating of ferrimagnetic particles and magnetic fluids: physical
      evaluation of their potential for hyperthermia. 1993.

PMID- 19848613
TI  - Hyperthermia classic commentary: 'Inductive heating of ferrimagnetic particles
      and magnetic fluids: Physical evaluation of their potential for hyperthermia' by
      Andreas Jordan et al., International Journal of Hyperthermia, 1993;9:51-68.
AB  - In order to increase the specific power absorption (SAR) in deep seated tumors,
      the idea was born to use AC magnetic fields in combination with magnetic
      particles instead of conventional E-field dominant systems. It was found, that
      nanoscaled particles were superior to micron-sized, multi-domain particles in
      terms of SAR due to different mechanisms how the field energy is converted into
      heat. Crucial parameters were identified for the human application of the method,
      such as the AC magnetic field amplitude and frequency, the nanoparticle
      composition and size distribution. Based on these physical and chemical
      relationships, a new thermotherapy method has been developed to heat up deep
      regional tumors using aqueous dispersions of iron oxide nanoparticles (magnetic
      fluids). Several clinical studies were initiated using this new heating
      technology. The results of the most advanced efficacy study for recurrent
      glioblastoma multiforme patients in combination with conventional radiation
      therapy are expected at the end of this year, 16 years after publication of this
      fundamental paper.

PMID- 19848615
TI  - Hyperthermia classic commentary: 'Simulation studies promote technological
      development of radiofrequency phased array hyperthermia' by Peter Wust et al.,
      International Journal of Hyperthermia 1996;12:477-494.
AB  - Simulation studies can estimate the potentials of regional hyperthermia based on
      the multi-antenna principle. They postulate an optimal parameter setup (phases,
      amplitudes) that should increase temperatures in heat treatments by 1 degrees C
      or more. However in praxi, slight inaccuracies and uncertainties accumulate in a
      way that the optimal adjustment is typically missed during a real treatment. The
      reasons for these errors are electrical and geometrical. A way out is an on-line
      control, which adapts the plans to the actual distributions. Magnetic resonance
      thermography is employed for on-line control, and control software has been
      developed. However, there is still a long way to reach the technological endpoint
      of multi-antenna systems for clinical applications.

PMID- 19848614
TI  - Simulation studies promote technological development of radiofrequency phased
      array hyperthermia. 1996.

PMID- 19848616
TI  - Intracellular hyperthermia: Nanobubbles and their biomedical applications.
AB  - Functionalised nanoparticles have been proposed as potential agents for non
      invasive therapies where an external source such as a laser or an electro
      magnetic wave is used to heat targeted particles for either drug release or
      malignant cell damage. It is desirable to have intracellular reactions to
      minimise the damage to health cells. However, it is still debatable from the
      thermal response point of view, whether intracellular hyperthermia is better than
      extracellular delivery due to conventional ideas of localisation of heat by
      nanoparticles. This work conducts an analytical study on the heating of a single
      nanoparticle by a pulsed laser and reveals the potential role of the formation of
      nanobubbles around heated particles. The rapid formation and contraction of
      bubbles around heated nanoparticles, associated with the propagation of pressure
      waves, could bring thermal-mechanical damage to surrounding cells at a dimension
      much larger than that of a nanoparticle. The challenges of the study of
      nanobubbles are highlighted and their potential healthcare implications are
      discussed.

PMID- 19848617
TI  - Characteristics and performance evaluation of the capacitive Contact Flexible
      Microstrip Applicator operating at 70 MHz for external hyperthermia.
AB  - PURPOSE: To characterise and evaluate the capacitive Contact Flexible Microstrip
      Applicator operating at 70 MHz, CFMA-70. This applicator is introduced for the
      treatment of superficial tumours with extension in depth beyond the range of
      regular superficial applicators. METHODS: E-field measurements were performed in
      an elliptical phantom filled with a saline solution using an E-field vector
      probe. E-field distributions and SAR patterns are compared to those of the CFMA
      434 and of 70 MHz waveguides. The applicator has been used for the treatment of 6
      patients with breast cancer with a tumour depth exceeding 4 cm. RESULTS: The
      effective heating depth of the CFMA-70 is 50% larger than for the CFMA-434. Its
      effective field size is 26 x 20 cm (aperture 29 x 20 cm), larger than for an
      equally sized CFMA-434. In contrast to the CFMA-434 the SAR pattern of this
      applicator is insensitive to the bolus thickness. Comparison to 70 MHz waveguides
      shows that the E-field component normal to the applicator is 100% larger for the
      CFMA-70. During clinical applications acceptable temperatures were realised for
      individual sessions (also at depth), but in many cases treatment limiting hot
      spots occurred close to superficial bony structures near the applicator edge.
      Both surface irregularities and the normal field component may be responsible.
      CONCLUSIONS: The CFMA-70 has adequate penetration depth for the treatment of
      superficial tumours exceeding a depth of 4 cm. However, the relatively large
      normal E-field component may induce treatment-limiting hot spots at tissue
      interfaces in the direction normal to the applicator's surface.

PMID- 19848619
TI  - Anti-foci for focused ultrasound.
AB  - An anti-focus is defined as the point where the pressure amplitude is zero. As an
      active protection means in focused ultrasound, the anti-focus was researched
      through simulations. A 513 element, 1 MHz, 15 cm focal depth, spherical shape
      transducer with a central hold was used for the simulation. An anti-focus was
      implemented with two different approaches and the simulation results were
      compared. First, the interference among foci was compared to the summation of the
      individual focus fields. Second, the interference among anti-foci was compared to
      the multiplication of the individual anti-focus fields. The minimum distance
      between a focus and an anti-focus was determined by the comparison between
      intended control values and the simulation results. The field simulation results
      indicate that the minimum distance to control the field is approximately 3 mm in
      the lateral direction and 15 mm in the axial direction. The results also
      demonstrate that a specific zone can be effectively protected with the addition
      of anti-foci and that the field can be effectively implemented by switching type
      amplifier systems. Results demonstrate the potential for anti-foci to
      significantly reduce the collateral damage in focused ultrasound through improved
      field control.

PMID- 19848618
TI  - Design of a water coupling bolus with improved flow distribution for multi
      element superficial hyperthermia applicators.
AB  - A water bolus used in superficial hyperthermia couples the electromagnetic (EM)
      or acoustic energy into the target tissue and cools the tissue surface to
      minimise thermal hotspots and patient discomfort during treatment. Parametric
      analyses of the fluid pressure inside the bolus computed using 3D fluid dynamics
      simulations are used in this study to determine a bolus design with improved flow
      and surface temperature distributions for large area superficial heat
      applicators. The simulation results are used in the design and fabrication of a
      19 x 32 cm prototype bolus with dual input-dual output (DIDO) flow channels.
      Sequential thermal images of the bolus surface temperature recorded for a step
      change in the circulating water temperature are used to assess steady state flow
      and surface temperature distributions across the bolus. Modelling and measurement
      data indicate substantial improvement in bolus flow and surface temperature
      distributions when changing from the previous single input-single output (SISO)
      to DIDO configuration. Temperature variation across the bolus at steady state was
      measured to be less than 0.8 degrees C for the DIDO bolus compared to 1.5 degrees
      C for the SISO water bolus. The new DIDO bolus configuration maintains a nearly
      uniform flow distribution and low variation in surface temperature over a large
      area typically treated in superficial hyperthermia.

PMID- 19848620
TI  - Improving locoregional hyperthermia delivery using the 3-D controlled AMC-8
      phased array hyperthermia system: a preclinical study.
AB  - BACKGROUND: The aim of this study is preclinical evaluation of our newly
      developed regional hyperthermia system providing 3-D SAR control: the AMC-8
      phased array consisting of two rings, each with four 70 MHz waveguides. It was
      designed to achieve higher tumour temperatures and improve the clinical
      effectiveness of locoregional hyperthermia. METHODS: The performance of the AMC-8
      system was evaluated with simulations and measurements aiming at heating a
      centrally located target region in rectangular (30 x 30 x 110 cm) and elliptical
      (36 x 24 x 80 cm) homogeneous tissue equivalent phantoms. Three properties were
      evaluated and compared to its predecessor, the 2-D AMC-4 single ring four
      waveguide array: (1) spatial control and (2) size of the SAR focus, (3) the ratio
      between maximum SAR outside the target region and SAR in the focus. Distance and
      phase difference between the two rings were varied. RESULTS: (1) Phase steering
      provides 3-D SAR control for the AMC-8 system. (2) The SAR focus is more
      elongated compared to the AMC-4 system, yielding a lower SAR level in the focus
      when using the same total power. This is counter-balanced by (3) a superficial
      SAR deposition which is half of that in the AMC-4 system, yielding a more
      favourable ratio between normal tissue and target SAR and allowing higher total
      power and up to 30% more SAR in the focus for 3 cm ring distance. CONCLUSION: The
      AMC-8 system is capable of 3-D SAR control and its SAR distribution is more
      favourable than for the 2-D AMC-4 system. This result promises improvement in
      clinical tumour temperatures.

PMID- 19848621
TI  - A literature survey on indicators for characterisation and optimisation of SAR
      distributions in deep hyperthermia, a plea for standardisation.
AB  - PURPOSE: To evaluate the predictive value of SAR indicators by assessing the
      correlation of a SAR indicator with the corresponding predicted temperature.
      Ultimately, this should lead to a number of verified SAR indicators for
      characterization and optimization of a predicted SAR distribution. METHODS: A
      literature survey is followed by an evaluation of the SAR indicators on their
      functionality, using a set of heuristic classification criteria. To obtain an
      objective assessment of the predictive value for SAR characterisation, all SAR
      indicators are evaluated by correlating the value of the SAR indicator to the
      predicted target temperature when heated with the BSD2000 Sigma 60 applicator.
      Two methods were followed. First, the specificity of the SAR indicator to target
      temperature was assessed for each of the 36 patient-specific models, using 30
      randomly chosen phase and amplitude settings. Secondly, each SAR indicator was
      used as a goal function to assess its suitability for optimisation purposes.
      RESULTS: Only a selected number of SAR indicators correlate well with
      tumour/target-temperature. Hence, for target-related properties, an adequate set
      of SAR indicators is found in the literature. For hotspots, modifications are
      desirable. For optimisation purposes, improved objective functions have been
      defined. CONCLUSIONS: From the correlation of the SAR indicators with tumour
      temperature, a preferred set of SAR indicators is derived: For target heating,
      'average SAR ratio', 'Hotspot-target SAR ratio', and 'homogeneity coefficient'
      provide suitable objective criteria, while for hotspot reduction, 'Hotspot-target
      SAR ratio' is considered the most useful indicator. For optimisation procedures,
      'Hotspot-target SAR ratio' is currently the most suitable objective function.

PMID- 19848851
TI  - Technologies for localization and diagnosis of prostate cancer.
AB  - The gold standard for detecting prostate cancer (PCa), systematic biopsy, lacks
      sensitivity as well as grading accuracy. PSA screening leads to over-treatment of
      many men, and it is unclear whether screening reduces PCa mortality. This review
      provides an understanding of the difficulties of localizing and diagnosing PCa.
      It summarizes recent developments of ultrasound (including elastography) and MRI,
      and discusses some alternative experimental techniques, such as resonance sensor
      technology and vibrational spectroscopy. A comparison between the different
      methods is presented. It is concluded that new ultrasound techniques are
      promising for targeted biopsy procedures, in order to detect more clinically
      significant cancers while reducing the number of cores. MRI advances are very
      promising, but MRI remains expensive and MR-guided biopsy is complex. Resonance
      sensor technology and vibrational spectroscopy have shown promising results in
      vitro. There is a need for large prospective multicentre trials that
      unambiguously prove the clinical benefits of these new techniques.

PMID- 19848852
TI  - A pilot trial in healthy volunteers to determine the reliability and accuracy of
      the oxygen compliance monitor, oxymon.
AB  - INTRODUCTION: Oxygen has been shown to improve morbidity, mortality and quality
      of life in hypoxaemic patients with chronic lung conditions. Assessing compliance
      has always been difficult and there are no accurate means of assessment available
      in clinical practice. We have trialled an oxygen compliance monitor called oxymon
      to address this. The aim of this study was to determine oxymons accuracy in
      recording oxygen use; including failure of oxygen supply and to alert users if
      oxygen supplies are disrupted. METHOD: The monitor continuously records oxygen
      flow and inspiratory pressure. We determined the accuracy of oxymon by
      determining the sensitivity and specificity of the oxygen and inspiratory
      pressure sensor. RESULTS: The accuracy of the oxygen and inspiratory pressure
      sensors is 96%. CONCLUSION: Oxymon is accurate; objectively measuring compliance
      to oxygen, recording duration of oxygen use and identifying failure in oxygen
      delivery from the oxygen source or lack of inspiratory pressure by alarming.

PMID- 19848853
TI  - Assessment of the antero-posterior and rotational stability of the anterior
      cruciate ligament analogue in a guided motion bi-cruciate stabilized total knee
      arthroplasty.
AB  - Abnormal knee kinematics and sagittal instability after most knee replacements
      are due in part to deficient anterior cruciate ligament (ACL) and posterior
      cruciate ligament (PCL) function. The guided motion bi-cruciate stabilized knee
      replacement aspires to stabilize the knee posteriorly and anteriorly by means of
      a cam-post mechanism. This investigation studies the ACL-stabilizing function of
      that mechanism in early flexion, and 25 knees that had undergone replacement with
      this implant were studied. Antero-posterior laxity at 15 degrees flexion was
      adequately restored for 76% (16/21) of the knees (side-to-side difference <3 mm
      on KT assessment), and 72% (18/25) knees exhibited a positive pivot shift test.
      The findings of this study suggest excellent early clinical outcomes for this
      implant, but the goal of replicating ACL function has only been partially
      achieved.

PMID- 19848854
TI  - Oven melting encapsulization of hypodermic needles by syringes.
AB  - The results of a study to determine the time and temperature conditions necessary
      to melt standard injection syringes are presented. The polypropylene syringes are
      melted to form a solid block of material encapsulating the attached stainless
      steel hypodermic needles, making them appropriate for further processing into
      other products. The desired result was obtained after two hours at 200 degrees C
      and can be replicated easily in a location such as a rural clinic in a developing
      nation.

PMID- 19848855
TI  - Spectral investigations of intraluminal impedance signals.
AB  - In this paper, an investigation of the spectral characteristics of intraluminal
      impedance signals using local Hilbert-Huang transform is presented. The impedance
      waveform may contain three main events: reflux event, swallow event and baseline
      region corresponding to no activity. The three events are analysed using local
      Hilbert-Huang transform to characterize the frequency contents of each event. In
      addition to the results of the Hilbert-Huang transform a time domain description
      of each event is presented.

PMID- 19848856
TI  - Insight into the dicrotic notch in photoplethysmographic pulses from the finger
      tip of young adults.
AB  - This study aims to investigate arterial stiffness in selected young adults by non
      invasively determining the characteristics of the photoplethysmographic dicrotic
      notch. A total of 15 volunteers participated in this study, divided into four
      groups by age and gender. Contour analysis was applied to analyse the
      photoplethysmographic dicrotic notch, including time-related and height-related
      parameters. The height of reflected wave, mirrored by the notch relative
      amplitude (NRA), was found to be significantly larger in the older group compared
      to the younger group (p = 0.016). The timing of the reflected wave, measured by
      three parameters, i.e. notch index (NI), notch latency (NL) and peak-to-notch
      latency (PTNL), significantly increased in the female group compared to the male
      group (all p < 0.02). The results confirm that arterial stiffness occurs in young
      adults, and demonstrate that a difference of arterial stiffness exists between
      young male and female. This study indicates that examining the characteristic
      notch of the PPG pulse could help in identifying differences of vascular
      activities.

PMID- 19848857
TI  - A comparison of photoplethysmography and ECG recording to analyse heart rate
      variability in healthy subjects.
AB  - Measures of heart rate variability (HRV) are widely used to assess autonomic
      nervous system (ANS) function. The signal from which they are derived requires
      accurate determination of the interval between successive heartbeats; it can be
      recorded via electrocardiography (ECG), which is both non-invasive and widely
      available. However, methodological problems inherent in the recording and
      analysis of ECG traces have motivated a search for alternatives.
      Photoplethysmography (PPG) constitutes another means of determining the timing of
      cardiac cycles via continuous monitoring of changes in blood volume in a portion
      of the peripheral microvasculature. This technique measures pulse waveforms,
      which in some instances may prove a practical basis for HRV analysis. We
      investigated the feasibility of using earlobe PPG to analyse HRV by applying the
      same analytic process to PPG and ECG recordings made simultaneously. Comparison
      of 5-minute recordings demonstrated a very high degree of correlation in the
      temporal and frequency domains and in nonlinear dynamic analyses between HRV
      measures derived from PPG and ECG. Our results confirm that PPG provides accurate
      interpulse intervals from which HRV measures can be accurately derived in healthy
      subjects under ideal conditions, suggesting this technique may prove a practical
      alternative to ECG for HRV analysis. This finding is of particular relevance to
      the care of patients suffering from peripheral hyperkinesia or tremor, which make
      fingertip PPG recording impractical, and following clinical interventions known
      to introduce electrical artefacts into the electrocardiogram.

PMID- 19848858
TI  - Computer simulation to aid the risk assessment of wheelchair and special seating
      systems used in transport.
AB  - The crashworthiness of occupied proprietary wheelchairs, which are transported in
      motor vehicles, is currently assessed by physical crash testing in accordance
      with ISO 7176-19. If such wheelchairs are modified to meet the needs of the
      occupant, e.g. the addition of special seating, environmental control systems or
      life support equipment, then those making the modifications take on the
      manufacturer's responsibilities, one of these being the assessment of the
      modified wheelchair's ability to withstand vehicle crash forces. Destructively
      testing bespoke wheelchair designs is not practical so, currently, the transport
      related risk is assessed using best engineering judgement. To improve this
      process virtual crash testing of the wheelchair and occupant was used. A modified
      crash criteria from ISO 7176-19 is proposed to enable assessment of the
      wheelchair's crashworthiness and provide the clinical engineer with an informed
      judgement of how both wheelchair alone and occupant and wheelchair together will
      behave in a crash.

PMID- 19848859
TI  - Development and validation of a user-friendly data logger (SUDALS) for use with
      flexible electrogoniometers to measure joint movement in clinical trials.
AB  - OBJECTIVE: Our aim was to develop and validate a user-friendly data logger system
      (SUDALS) for use with flexible electrogoniometry. METHODS: Data pertaining to
      flexion/extension of the knee from 10 normal subjects were collected during a
      range of activities of daily living (ADL) such as walking, ascending and
      descending stairs, getting in and out of a chair and deep squatting. The
      accuracy, reliability and reproducibility of the data from SUDALS were verified
      by comparing against the data simultaneously collected from the Vicon system.
      RESULTS: The results of these studies indicate that the SUDALS together with
      flexible electrogoniometers is able to produce stable, precise, accurate and
      repeatable knee flexion/extension angles with little variation existing between
      the data produced by the SUDALS, the Vicon system and that reported in the
      literature. CONCLUSION: The SUDALS together with flexible electrogoniometers is a
      useful clinical tool, capable of recording knee flexion/extension angles
      accurately during ADL.

PMID- 19848860
TI  - Comparative study of different control techniques for the regulation of blood
      glucose level in diabetic patients.
AB  - Blood glucose regulation is of a great concern for insulin-dependant patients
      with excessive glucose in blood (hyperglycaemia), or low glucose profile
      (hypoglycaemia) due to excess insulin delivery. Both conditions can cause
      dangerous complications for diabetic patients, and hence glucose regulation in
      blood is of prime importance. Insulin pumps are used to deliver insulin in small
      quantities, allowing the glucose level to remain as close as possible to that of
      non-diabetics (near 100 mg dl(-1)). Different control techniques are used to
      maintain the glucose level and most of them depend on an exact mathematical or
      empirical model of insulin-glucose interaction. Recently, we have proposed
      different controllers that are based on fuzzy logic and so do not use
      mathematical modelling, which in general is nonlinear, complex and suffers from
      uncertainties. PI fuzzy controllers are physically related to classical PI and
      PID controllers, which are extremely popular. The parameter settings of classical
      and fuzzy logic controllers are based on deep common physical background. In this
      manuscript, a comparative study is proposed to evaluate the use of fuzzy logic
      controllers over other conventional controllers such as PI and PID controllers to
      maintain the blood glucose level within a normoglycaemic average especially when
      a diabetic patient is subjected to different conditions.

PMID- 19848861
TI  - An effective method for skin blood flow measurement using local heat combined
      with electrical stimulation.
AB  - Electrical stimulation (ES) is a modality used to increase skin blood flow (SBF)
      and to aid in wound healing. A greater SBF in non wounded skin is induced if ES
      is used in a warm environment compared to a thermoneutral environment, where ES
      is usually applied. Therefore, in this paper, a method to investigate the effect
      of local heating and ES on the SBF is developed. A total of 33 males (18-40
      years) were divided into group G (n = 15) who received the ES during a global
      heating protocol and group L (n = 18) who received ES during a local heating
      protocol. In the global heating protocol, ES (30 Hz, 250 micros) was applied for
      15 min on the subject's thigh in thermoneutral (25 +/- 0.5 degrees C) and warm
      (35 +/- 0.5 degrees C) environments. In the local heating protocol, ES was
      applied for 15 minutes at 25 degrees C, 35 degrees C and 40 degrees C local skin
      temperatures. A laser Doppler imager measured the SBF in both protocols pre,
      during, and post ES. The results of the experiment showed the significant
      differences in the SBFs were found at pre, during, and post ES in a thermoneutral
      environment or when the skin was locally cooled to 25 degrees C. The SBFs were
      significantly increased during and post ES after global heating or during local
      heating at 35 degrees C and 40 degrees C. There were no significant differences
      in SBFs between the warm environment and at 35 degrees C of local heating.
      However, the SBF response to ES was the highest at 40 degrees C of local heating.
      Thus, ES during local heating of the skin, as well as during global heating is an
      effective method to increase SBF.

PMID- 19849324
TI  - The current role of amphotericin B lipid complex in managing systemic fungal
      infections.
AB  - BACKGROUND: An increase in the number of immunocompromised patients has led to a
      rising burden of systemic fungal infections. Historically, conventional
      amphotericin B has been used to treat these infections due to its broad spectrum
      of activity. The development of lipid-based amphotericin B agents, such as
      Abelcet * (ABLC), has allowed clinicians to take advantage of the broad spectrum
      of activity of amphotericin B while reducing adverse events. As well as this, a
      number of new antifungal agents have been developed in recent years which have
      significantly added to the treating physician's antifungal armamentarium. *
      Abelcet is a registered trade name of Cephalon Ltd, Herts, UK. OBJECTIVES: Review
      the clinical data that support the use of ABLC and discuss the evidence for its
      continuing role in the treatment of invasive fungal infections in light of the
      introduction of newer antifungal agents. METHODS: Published studies were
      identified by searching the MEDLINE database and the Cochrane Centre for Reviews
      up to August 2009. The search was conducted using the following key words:
      Amphotericin, Lipid, Abelcet, AmBisome, Efficacy, Nephrotoxicity, Renal,
      Toxicity. FINDINGS: ABLC is effective and well-tolerated in the treatment of
      systemic fungal infections and remains a valuable therapeutic option in a variety
      of immunocompromised patients due to its broad antifungal spectrum and rarity of
      resistance. LIMITATIONS: Data from randomised controlled trials of lipid-based
      amphotericin B formulations, as well as head-to-head comparison studies between
      ABLC and other antifungal agents are limited. In addition, the review uses a
      narrative approach and relies to a great extent on the authors' personal views
      and experiences.

PMID- 19849639
TI  - HRQL and medication satisfaction in children with ADHD treated with the
      methylphenidate transdermal system.
AB  - OBJECTIVE: To evaluate the impact of methylphenidate transdermal system (MTS) on
      health-related quality of life (HRQL) and medication satisfaction in children
      with attention-deficit/hyperactivity disorder (ADHD) as well as to identify
      potential moderators of HRQL and medication satisfaction. RESEARCH DESIGN AND
      METHODS: Children aged 6-12 years diagnosed with ADHD were enrolled (N = 128) and
      115 children completed the study. MTS dose was optimized over 5 weeks using 10-,
      15-, 20-, or 30-mg patches worn for 9 hours. The efficacy of 4- and 6-hour wear
      times was then assessed in an analog classroom setting in a randomized, placebo
      controlled, double-blind, three-way crossover design study. MAIN OUTCOME
      MEASURES: The ADHD Impact Module-Children (AIM-C), a validated HRQL instrument,
      was used to assess the impact of ADHD symptoms on children and their families.
      Satisfaction with MTS use was assessed via a Medication Satisfaction Survey
      (MSS). A parent or legally appointed representative (LAR) completed the measures.
      Tolerability was monitored by spontaneous adverse event reporting. RESULTS: Mean
      scores on AIM-C child and family HRQL scales improved from baseline to endpoint
      across all MTS doses and the magnitude of improvement increased with time from
      baseline. Improvement was noted for behavior, missed doses, worry, and economic
      impact AIM-C scores. Overall, parents/LARs indicated a high level of satisfaction
      with their child's use of MTS (Visit 7 [92.1%]; Visit 10 [89.1%]). Most treatment
      emergent adverse events (TEAEs) were mild to moderate. The most frequent TEAEs
      included decreased appetite (28%), headache (21%), insomnia (20%), and abdominal
      pain (12%). CONCLUSIONS: At study endpoint, MTS treatment of ADHD was associated
      with robust improvement in child and family HRQL, key economic impact items, and
      overall medication satisfaction with the effectiveness and ease of use of MTS as
      an ADHD treatment. Also, the majority of MTS TEAEs were mild to moderate in
      severity. Limitations of this study included the potential for a significant halo
      effect when measuring HRQL and medication satisfaction as well as the uncertainty
      regarding whether the improvements seen over this relatively short study duration
      would be sustainable long term. CLINICAL TRIAL REGISTRATION: #NCT00151970.

PMID- 19849649
TI  - Depressive symptoms predict postoperative disability among patients with lumbar
      spinal stenosis: a two-year prospective study comparing two age groups.
AB  - PURPOSE: To examine the importance of preoperative and recovery phase depressive
      symptoms in two age groups of patients with lumbar spinal stenosis (LSS) with
      respect to surgery outcome 2 years postoperatively. METHOD: Ninety-six patients
      with symptomatic LSS underwent decompressive surgery. Data were collected with
      self-report questionnaires before surgery and 3 months, 6 months, 1 year and 2
      years postoperatively. Depression was assessed with the Beck Depression Inventory
      (BDI). Depressive burden was examined by compiling the sum of preoperative, 3
      month and 6-month BDI scores. Physical functioning and pain were assessed with
      the Oswestry Disability Index, Walking ability and VAS. In the analyses, the
      subjects were divided into two groups according to the median age (62 years).
      RESULTS: Depressive burden was a strong predictor of disability at the 2-year
      postoperative phase both in younger and elderly patients with LSS. A notable
      proportion (20%) of the younger patients had considerable depressive
      symptomatology 2 years after the surgery, whereas in the older age group this
      proportion was 8%. CONCLUSION: The results suggest that there is a strong
      relationship between depressive symptoms and disability among postoperative
      patients with LSS. Identifying and treating patients with preoperative and
      postoperative depressive symptoms may be a useful strategy for improving LSS
      surgery outcomes.

PMID- 19849650
TI  - Meta-analysis of doripenem vs comparators in patients with pseudomonas infections
      enrolled in four phase III efficacy and safety clinical trials.
AB  - OBJECTIVE: Pseudomonas aeruginosa is a difficult-to-treat bacterial pathogen
      often isolated from patients with serious nosocomial infections. The goal of this
      analysis is to present the clinical and microbiologic effectiveness of doripenem
      in the treatment of infections due to P. aeruginosa. RESEARCH DESIGN AND METHODS:
      A meta-analysis was conducted on the subset of subjects enrolled in four
      randomized phase III clinical trials of doripenem in subjects with complicated
      intra-abdominal infections (cIAI) and nosocomial pneumonia/ventilator-associated
      pneumonia (NP/VAP) due to P. aeruginosa. Clinical and microbiologic success was
      determined by infection and across the two infections. RESULTS: Clinical success
      rates for modified intent-to-treat (mITT) subjects with P. aeruginosa in the cIAI
      and NP/VAP groups were 78.7% (37/47) and 59.6% (31/52), respectively, following
      treatment with doripenem versus 74.3% (26/35) and 32.8% (19/58), respectively,
      for subjects in the comparator groups (p < 0.05 for difference in success rates
      across infection types). Microbiologic eradication rates also favored doripenem,
      although the differences did not achieve statistical significance. The weighted
      difference (doripenem minus comparator) for the mITT population in clinical
      success rates between doripenem and the comparator agents was 16.0% (95% CI:
      3.1%, 29.0%) and for microbiologic eradication rates was 9.1% (95% CI: -4.2%,
      22.3%). The proportion of subjects reporting one or more treatment-emergent
      adverse events or serious adverse events was similar for doripenem and the
      comparator agents. Fourteen doripenem and 14 comparator subjects died during the
      study. Limitations of this retrospective meta-analysis also include the
      qualitative heterogeneity of the data, and a selected, narrow population of
      moderately ill clinical trial subjects included in the analysis. Due to
      limitations, these data may not be generalizable to all populations and should be
      considered hypothesis generating. CONCLUSION: The weighted difference in clinical
      success rates for subjects with cIAI and NP/VAP infections caused by P.
      aeruginosa was in favor of doripenem, with the relative benefit of doripenem
      compared with the comparator agents similar across the two infections.

PMID- 19849659
TI  - Neuron protection as a therapeutic target in acute ischemic stroke.
AB  - Involvement of various neurotransmitters and neuromodulators have been shown to
      contribute to the ischemic injury and neuronal death associated with stroke Role
      of excitatory amino acid receptor activation, calcium overload, nitric oxide, and
      oxidative stress in the pathogenesis of ischemic brain damage is well
      established. Several new strategies are currently emerging, based on recent
      advances in our understanding of molecular pathways that could be considered as
      potential therapeutic targets. For example reactive oxygen species (ROS) are
      important contributors to the secondary injury cascade following traumatic brain
      injury (TBI), and ROS inhibition has consistently been shown to be
      neuroprotective following experimental TBI and brain ischemia. Furthermore, more
      recently, some authors concluded that nonanticoagulant 3K3A-APC exhibits greater
      neuroprotective efficacy with no risk for bleeding compared with drotrecogin-alfa
      activated, a hyperanticoagulant form of APC. Excessive calcium entry into
      depolarized neurons contributes significantly to cerebral tissue damage after
      ischemia. Included in the sequence of events leading to neuronal death in
      ischemic tissue following stroke is an excessive and toxic rise in the
      intracellular Ca(2+)-concentration, predominantly due to an influx of Ca2+
      through nonselective cation-channels as well as Ca(2+)-channels.. Some authros
      conducted a study to investigate whether the enhancement of GABA receptor
      activity could inhibit NMDA receptor-mediated nitric oxide (NO) production by
      neuronal NO synthase (nNOS) in brain ischemic injury. The results showed that
      both the GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist
      baclofen had neuroprotective effect, and the combination of two agonists could
      significantly protect neurons against death induced by ischemia/reperfusion. On
      this basis we conclude that neuroprotection for ischemic stroke refers to
      strategies, applied singly or in combination, that antagonize the injurious
      biochemical and molecular events that eventuate in irreversible ischemic injury.
      There has been a recent explosion of interest in this field, with over 1000
      experimental papers and over 400 clinical articles appearing within the past 6
      years. These studies, in turn, are the outgrowth of three decades of
      investigative work to define the multiple mechanisms and mediators of ischemic
      brain injury, which constitute potential targets of neuroprotection.

PMID- 19849660
TI  - Antiplatelet treatment in ischemic stroke treatment.
AB  - Antiplatelets represent a diverse group of agents that share the ability to
      reduce platelet activity through a variety of mechanisms. Antithrombotic agents
      are effective in the secondary prevention of ischemic strokes. Most strokes are
      caused by a sudden blockage of an artery in the brain (called an ischaemic
      stroke) that is usually due to a blood clot. Immediate treatment with
      antiplatelet drugs such as aspirin may prevent new clots from forming and hence
      improve recovery after stroke. Several studies have evaluated the role of one
      antiplatelet agent, aspirin, in reducing stroke severity. The International
      Stroke Trial (IST) of 20,000 patients with acute stroke from other countries. In
      this study there was a significant 14% proportional reduction in mortality during
      the scheduled treatment period (343 [3.3%] deaths among aspirin-allocated
      patients vs 398 [3.9%] deaths among placebo-allocated patients; 2p = 0.04). There
      were significantly fewer recurrent ischaemic strokes in the aspirin-allocated
      than in the placebo-allocated group (167 [1.6%] vs 215 [2.1%]; 2p = 0.01) but
      slightly more haemorrhagic strokes (115 [1.1%] vs 93 [0.9%]. Few studies examined
      the role of ticlopidin in acute stroke setting the results showed treatment with
      ticlopidine improved the neurologic outcome. In the Examining the Safety of
      Loading of Aspirin and Clopidogrel in Acute Ischemic Stroke and TIA (LOAD) study,
      40 consecutive ischemic stroke patients were treated with 325 mg of aspirin and
      375 mg of clopidogrel within 36 hours of symptom onset. Overall, 37.5% (n = 15)
      of the patients had an improvement of 2 or more points on the NIHSS 24 hours
      after antiplatelet administration. The antiplatelet efficacy of aspirin in
      preventing secondary stroke was established by three studies conducted in the
      late 1980s and early 1990s: the Swedish Aspirin Low-dose Trial (SALT) trials have
      demonstrated that aspirin-even in doses as low as 30 mg/day-reduces secondary
      stroke, MI, or vascular death in patients with. Clopidogrel and aspirin have been
      used in combination in patients with diverse arterial vascular diseases However,
      combinations of antithrombotic agents do not necessarily improve clinical
      efficacy and are typically associated with increased toxicity.

PMID- 19849662
TI  - Thrombolysis for acute ischemic stroke.
AB  - In the last decennium, thrombolytic therapy has changed the management of acute
      ischemic stroke. Randomized clinical studies have demonstrated that intravenous
      thrombolysis with tissue plasminogen activator improves functional outcomes.
      Recently the time window for intravenous thrombolysis has been extended from 3 to
      4.5 hours after stroke onset, which will allow more stroke patients to benefit
      from this treatment. Currently several studies are investigating how to improve
      recanalization rates of thrombolytic therapy. In this review several aspects of
      intravenous and intra-arterial thrombolysis are discussed.

PMID- 19849661
TI  - Dyslipidemia as a risk factor for ischemic stroke.
AB  - Ischemic stroke is a major cause of morbidity and mortality. Whereas dyslipidemia
      is a major risk factor for coronary heart disease (CHD), its role in the
      pathogenesis of ischemic stroke is less clear. Epidemiological studies have
      provided conflicting findings regarding the association of dyslipidemia with
      ischemic stroke. Overall, elevated LDL-C levels appear to increase the risk of
      ischemic stroke. Low HDL-C levels also appear to be associated with a greater
      risk whereas the importance of high triglyceride levels is less clear. The
      discordant results of observational studies might result from the heterogeneity
      of stroke, since dyslipidemia is less likely to play a major role in the
      pathogenesis of some ischemic stroke subtypes (e.g. lacunar and cardioembolic
      strokes) and elevated LDL-C levels might increase the risk of hemorrhagic stroke.
      In clinical trials, statins consistently reduced the risk of ischemic stroke in
      patients with or without CHD whereas the data on the effects of other lipid
      modifying drugs on stroke risk are limited. In patients with a previous stroke,
      statins reduce the risk of both ischemic stroke and other vascular events but
      also increase the risk of hemorrhagic stroke. Accordingly, current guidelines
      recommend the same lipid targets for the primary and secondary prevention of both
      stroke and CHD. In addition, stroke and transient ischemic attacks of carotid
      origin are considered CHD risk equivalents. Nevertheless, more trials are
      required to identify which patients with stroke but without CHD will benefit more
      from statin treatment.

PMID- 19849663
TI  - Blood pressure as a therapeutic target in stroke.
AB  - Stroke, as a clinical manifestation of the cardiovascular diseases, is one of the
      leading causes of death and disability in both developed and developing
      countries. Hypertension is by far, the most important risk factor for stroke.
      Epidemiological data indicate that the risk of stroke increases with both
      systolic and diastolic blood pressure elevation, from levels of 115/75 mmHg. It
      is also evident that most adults worldwide have values above these limits, thus
      emphasizing the importance of blood pressure as a risk factor for stroke.
      Clinical trials of antihypertensive treatment, both in studies that have compared
      active drugs against placebo or in those comparing different types of drugs have
      clearly demonstrated a protective effect of blood pressure reduction in the
      prevention of stroke. The degree of protection is directly related to blood
      pressure reduction and, the lower the level, the better the prognosis. Although
      data on secondary stroke prevention are scarcer, studies also seem to indicate
      that lowering blood pressure with antihypertensive treatment protects against
      stroke recurrence. At the present moment there is still uncertainty on 2
      different aspects regarding the relationship between antihypertensive treatment
      and stroke. First, the blood pressure management during acute stroke has not
      adequately investigated in clinical trials. Second, the possibility of a
      protective role of specific types of antihypertensive drugs beyond blood pressure
      reduction is a matter of debate. Independently of these unresolved issues,
      prevention of hypertension development by lifestyle changes and adequate
      treatment and control to the hypertensive population will be a very effective
      measure in reducing stroke incidence, stroke recurrence, and stroke mortality.

PMID- 19849664
TI  - Glucose blood levels as a therapeutic target in acute ischaemic stroke setting.
AB  - Ischaemic stroke is extremely common in western societies contributing to 70-85%
      of strokes, one of the leading causes of mortality and long-term disability.
      Despite advancement in preventive measures, the total number of strokes is set to
      rise in the future due to increasing numbers of aging populations across the
      world. Diabetes as a risk factor for stroke has been well established. There are
      also emerging evidence to suggest glucose level management in acute stroke phase
      as a therapeutic target may be beneficial, albeit remains controversial. One of
      the issues in difficulty in interpreting study findings is their heterogeneity.
      In this article, we provide epidemiological, basic science, clinical
      observational and trial evidence leading to the current practice of regarding
      blood glucose as the therapeutic target in acute ischaemic stroke setting.

PMID- 19849665
TI  - Inflammation as a therapeutic target in acute ischemic stroke treatment.
AB  - Animal models of focal ischaemia induced by middle cerebral artery occlusion
      (MCAO) provide most evidence for cellular inflammatory responses in stroke.
      Permanent MCAO results in a modest neutrophil infiltration at 24 h after
      ischaemia, predominantly around arterial vessels at the margins of infarction,
      whereas MCAO with subsequent reperfusion is associated with substantial
      infiltration by neutrophils throughout the entire infarct. Several studies show
      that C-reactive protein (CRP), an inflammatory marker, is associated with stroke
      outcomes and future vascular events. Several drugs, especially
      hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), have been
      demonstrated to reduce hsCRP levels independently of their effects on plasma
      cholesterol. Various cytokines were shown to be expressed in the injured brain.
      Recent investigations demonstrated that mRNAs of above cytokines were induced in
      the ischemic rat brain. TNF-alpha is a pleiotropic cytokine that mediates key
      roles in many physiological and pathological cellular processes including acute
      and chronic inflammation, programmed cell death or apoptosis, anti-tumor
      responses, and infection. Pharmaceutical industry to search a small molecule TNF
      inhibitor have taken multiple strategies. Significant protection after in vivo
      oral use of SB-239063 from brain injury and neurological deficits was observed in
      one study. In the same study significant protection from brain injury and
      neurological deficits was also demonstrated due to i.v post-stroke treatment with
      the same compound. Leukocyte-endothelial adhesion process consists of several
      steps, beginning with rolling of the leukocyte on the endothelial surface until
      it has slowed down to such a degree that it sticks to the endothelium. Treatment
      with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients
      with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST).
      Unfortunately, the case fatality rate in this trial was significantly higher in
      the enlimomab patient group than in the placebo group. Furthermore, experimental
      data have shown that focal cerebral ischemia induces a time-dependent activation
      of granulocytes, lymphocytes, and macrophages. 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.

PMID- 19849666
TI  - Wild-type and missense mutants of retinoschisin co-assemble resulting in either
      intracellular retention or incorrect assembly of the functionally active octamer.
AB  - The X-linked disease retinoschisis is caused by mutations in the RS1 gene
      encoding retinoschisin, most commonly missense mutations leading to a lack of
      secretion of functional protein. One potential approach to treat this disease
      would be the introduction of the wild-type protein by gene therapy in affected
      individuals. Retinoschisin normally forms homo-octamers, so co-expression of the
      wild-type protein with the mutant could result in their co-assembly. In the
      present study, we show that retinoschisin assembles into an octamer before
      transport from the endoplasmic reticulum and that co-assembly of wild-type and
      mutant protein can occur when they are co-expressed in the same cell. This co
      assembly results in the retention of some, but not all, expressed wild-type
      retinoschisin. Moreover, when the wild-type protein is expressed with a missense
      mutant that is normally secreted, co-assembly occurs resulting in the secretion
      of a heterogeneous mixture of oligomers. Missense mutations of retinoschisin
      which cause intracellular retention also lead to an unfolded protein response.
      However, this is not sufficient to decrease cell viability suggesting that the
      pathology of the disease is not likely to be linked to programmed cell death.

PMID- 19849667
TI  - The molecular basis of the effect of temperature on enzyme activity.
AB  - Experimental data show that the effect of temperature on enzymes cannot be
      adequately explained in terms of a two-state model based on increases in activity
      and denaturation. The Equilibrium Model provides a quantitative explanation of
      enzyme thermal behaviour under reaction conditions by introducing an inactive
      (but not denatured) intermediate in rapid equilibrium with the active form. The
      temperature midpoint (Teq) of the rapid equilibration between the two forms is
      related to the growth temperature of the organism, and the enthalpy of the
      equilibrium (DeltaHeq) to its ability to function over various temperature
      ranges. In the present study, we show that the difference between the active and
      inactive forms is at the enzyme active site. The results reveal an apparently
      universal mechanism, independent of enzyme reaction or structure, based at or
      near the active site, by which enzymes lose activity as temperature rises, as
      opposed to denaturation which is global. Results show that activity losses below
      Teq may lead to significant errors in the determination of DeltaG*cat made on the
      basis of the two-state ('Classical') model, and the measured kcat will then not
      be a true indication of an enzyme's catalytic power. Overall, the results provide
      a molecular rationale for observations that the active site tends to be more
      flexible than the enzyme as a whole, and that activity losses precede
      denaturation, and provide a general explanation in molecular terms for the effect
      of temperature on enzyme activity.

PMID- 19849669
TI  - A persistent gastric feeding tube.

PMID- 19849670
TI  - A case of near-drowning: a case for routine cerebral monitoring.
AB  - A 6-week-old infant presenting with near-drowning was medically paralysed and
      ventilated on admission. Status epilepticus was found on cerebral function
      monitoring, without which the diagnosis would have been missed or delayed for
      many hours. This case illustrates the value of cerebral function monitoring for
      patients in intensive care, where clinical signs of seizure activity are
      frequently masked by paralysis and sedation. CONCLUSION: Limited availability of
      electroencephalogram (EEG) and cerebral function monitoring (CFM) in paediatric
      intensive care may inadvertently delay diagnosis and appropriate treatments and
      so adversely affect outcomes. We propose that round-the-clock cerebral function
      and/or EEG monitoring should be available in all centres that provide paediatric
      intensive care.

PMID- 19849671
TI  - Physical activity levels and estimated energy expenditure in overweight and
      normal-weight 11-year-old children.
AB  - AIM: To objectively evaluate physical activity and energy expenditure in
      overweight and normal-weight 11-year-old children. METHODS: The final sample
      consisted of 91 children (32 overweight and 59 normal-weight children), mean age
      (SD) = 11.3 (0.2) years. Energy expenditure and physical activity were assessed
      during two weekdays and two weekend days using a multiple-sensor body monitor
      (SenseWear Armband; BodyMedia Inc., Pittsburgh, PA, USA). RESULTS: Time spent in
      physical activity was higher in normal-weight compared with overweight children
      (p = 0.002). The highest level of physical activity was noted in normal-weight
      boys [mean (SD) = 258 (114) min/day] and the lowest in overweight girls [mean
      (SD) = 136 (59) min/day] (p = 0.002). In contrast, energy expended during
      physical activity did not differ between normal-weight and overweight children
      (2.6 and 2.7 MJ/day, respectively, p = 0.89). The average decrease in physical
      activity at weekends was 39 min in overweight children (from 166 to 127 min/day)
      and 27 min in their normal-weight counterparts (from 230 to 203 min/day).
      CONCLUSION: Overweight children engaged in less physical activity of both
      moderate and vigorous intensity compared with their normal-weight peers. Both
      overweight and normal-weight children were less active at weekends than on
      weekdays. Initiatives aiming to increase physical activity of overweight children
      at weekends are warranted.

PMID- 19849672
TI  - Frontal brain activation in young children during picture book reading with their
      mothers.
AB  - AIM: This study was to measure changes in frontal brain activation in young
      children during picture book reading with their mothers. METHODS: The cross
      sectional sample consisted of 15 young Japanese children (eight girls and seven
      boys, mean age 23.1 +/- 3.4). Two experimental tasks were presented as follows:
      Task 1 (picture book reading with their mothers); Task 2 (viewing of book-on
      video). Duration of task stimulus was 180-sec and the 60-sec interval was filled.
      Brain activation was measured using an optical topography system. RESULTS:
      Significant increases in oxy-Hb were observed in both right and left frontal
      areas in response to Task 1 compared with Task 2. There were significant
      correlations between child's brain activity and mothers' and children's verbal
      nonverbal behaviours. CONCLUSION: There was greater frontal lobe activation in
      children when they were engaged in a picture book reading task with their
      mothers, as opposed to passive viewing of a videotape in which the story was read
      to them. Social and verbal engagement of the mother in reading picture books with
      her young child may mediate frontal brain activity in the child.

PMID- 19849673
TI  - Alternaria sensitization and allergic rhinitis with or without asthma in the
      French Six Cities study.
AB  - BACKGROUND: Allergic sensitization to Alternaria has been related to asthma in
      various studies, but its association with allergic rhinitis is still
      controversial. OBJECTIVES: The aim of this study was to assess at the population
      level the relationships in childhood between Alternaria sensitization and 'past
      year rhinoconjunctivitis' (PYRC), 'ever hay fever' (EHF) and 'ever allergic
      rhinitis caused by allergens other than pollens' (EAR) according to the presence
      or the absence of asthma. METHODS: This study is part of the Six Cities Study,
      the French contribution to the International Study of Asthma and Allergies in
      Childhood (ISAAC) Phase II. Children underwent skin prick test (SPT) to
      Alternaria and parents filled a standardized medical questionnaire. RESULTS: Some
      6726 children with a mean age of 10 years were examined. The overall prevalence
      of Alternaria sensitization was 2.8%, 0.8% for monosensitization. Prevalences of
      symptoms in sensitized children were 27.7% for PYRC, 27.0% for EHF and 30.4% for
      EAR. Adjusted Odds Ratios (OR) between Alternaria sensitization and allergic
      rhinitis phenotypes were 2.34 (95% confidence interval: 1.51-3.63) for PYRC, 2.40
      (1.65-3.50) for EHF and 2.95 (2.05-4.23) for EAR. The relationship still remained
      in the case of monosensitization to Alternaria for both PYRC and EAR when
      excluding the asthmatic children [OR = 3.87 (1.54-9.78) and 2.88 (1.10-7.55)
      respectively]. CONCLUSION: In our population-based sample of children, we found a
      link between Alternaria sensitization and allergic rhinitis, independently of
      asthma, which is compatible with the mechanisms of deposition of Alternaria in
      the upper airways.

PMID- 19849675
TI  - Peri-operative management of a patient with hereditary angioedema undergoing
      laparoscopic cholecystectomy.
AB  - Hereditary angioedema is a rare genetic disorder resulting from an inherited
      deficiency or dysfunction of the C1-esterase inhibitor of the classic complement
      pathway. It is characterised by recurrent episodes of angioedema, without
      urticaria or pruritus, most often affecting the skin or the mucosal tissues of
      the upper respiratory and gastrointestinal tracts. We describe the peri-operative
      care of a woman with hereditary angioedema undergoing laparoscopic
      cholecystectomy with emphasis on the role of anaesthetists as peri-operative
      physicians.

PMID- 19849674
TI  - Lipid resuscitation in a carnitine deficient child following intravascular
      migration of an epidural catheter.
AB  - A child with cerebral palsy and carnitine deficiency developed ventricular
      arrhythmias with loss of cardiac output during elective surgery under general
      anaesthesia with concomitant epidural analgesia. Sinus rhythm was restored on
      administration of adrenaline, but hypotension persisted despite resuscitation.
      Bolus administration of 0.8 ml*kg(-1) (20 ml) lipid emulsion resulted in rapid
      improvement in cardiac output. Blood samples taken before and after the lipid
      bolus did not demonstrate toxic concentrations of bupivacaine. This case suggests
      that carnitine deficiency may increase susceptibility to bupivacaine
      cardiotoxicity.

PMID- 19849676
TI  - The Scottish Audit of Surgical Mortality: a review of areas of concern related to
      anaesthesia over 10 years.
AB  - The Scottish Audit of Surgical Mortality is a voluntary, peer reviewed, critical
      event analysis of patients who die under the care of consultant surgeons in acute
      hospitals in Scotland. The anaesthetic contribution to surgical mortality over a
      10-year period from 1996 was reviewed. The total number of deaths was 44 230 or
      1.5% of all admissions. Forty thousand, eight hundred and ninety-six deaths (92%)
      were audited. Deaths after elective surgery declined over 10 years. Over 80% of
      deaths followed emergency admission. The number of deaths where an anaesthetist
      was present was 16 981 or 0.6% of all admissions. Anaesthetic areas of concern
      were identified in 8% of deaths. Of these, 43% were related to pre-operative
      assessment. Anaesthesia also played a part in a further 18% of deaths where
      decision making was shared with the surgical team. Of these, 41% were related to
      access to critical care. A further 24% related to communication failures,
      principally when the operation should not have been done or was unnecessary.

PMID- 19849677
TI  - The Parker Flex-Tip tube for nasotracheal intubation: the influence on nasal
      mucosal trauma.
AB  - We tested our hypothesis that use of the Parker Flex-Tip tracheal tube could
      reduce the incidence of nasal mucosal trauma during nasotracheal intubation when
      compared with a conventional tip tracheal tube. One hundred and two patients, who
      were scheduled for elective oral surgery in which nasotracheal intubation was
      indicated to optimise the surgical approach, were recruited into this study.
      Either a Flex-Tip tracheal tube or a conventional tip tracheal tube was chosen
      randomly for each nasotracheal intubation. The incidence of epistaxis using the
      Flex-Tip tracheal tube (6 (11.8%)) was significantly lower than that with the
      conventional tip tracheal tube (18 (35.3%); p = 0.009). Nasal pain due to
      intubation, rated on a 100-mm visual analogue scale, was less intense with the
      Flex-Tip tracheal tube (median, (10th-90th percentile) 19 (12-28) mm compared
      with the conventional tip tracheal tube (30 (22-35) mm; p < 0.001). The Flex-Tip
      tracheal tube thus appeared to reduce the incidence of nasal mucosal trauma
      during nasotracheal intubation and the incidence of post-intubation nasal pain,
      compared with the conventional tip tracheal tube.

PMID- 19849678
TI  - Litigation related to drug errors in anaesthesia: an analysis of claims against
      the NHS in England 1995-2007.
AB  - Ninety-three claims (total cost 4,915,450 pounds) filed under 'anaesthesia' in
      the NHS Litigation Authority database between 1995 and 2007, alleging patient
      harm directly by drug administration error or by an allergic reaction, were
      analysed. Alleged errors were categorised using systems employed by the National
      Coordinating Council for Medication Error Reporting and Prevention, the American
      Society of Anesthesiologists Closed Claims Project and the UK Health and Safety
      Executive. The severity of outcome in each claim was categorised using adapted
      National Patient Safety Agency definitions. Sixty-two claims involved alleged
      drug administration errors (total cost 4,283,677 pounds) and 15 resulted in
      severe harm or death. Half alleged the administration of the wrong drug, in most
      (16) a neuromuscular blocker. Of the claims alleging the wrong dose had been
      given (25), nine alleged opioid overdose including by neuraxial routes. The most
      frequently recorded adverse outcomes were awake paralysis (19 claims; total cost
      182,347 pounds) and respiratory depression requiring intensive care treatment (13
      claims; total cost 2,752,853 pounds). Thirty-one claims involved allergic
      reactions (total cost 631,773 pounds). In 20 claims, the patient allegedly
      received a drug to which they were known to be allergic (total cost 130,794
      pounds). All claims in which it was possible to categorise the nature of the
      error involved human error. Fewer than half the claims appeared likely to have
      been preventable by an 'ideal double checking process'.

PMID- 19849679
TI  - Dental implant removal to facilitate suspension laryngoscopy and laser treatment
      of an obstructed airway.
AB  - A 29-year-old patient presented with dysphonia, dysphagia and a progressive
      history of stridor over 6 weeks. His past medical history included childhood
      nasolabial rhabdomyosarcoma treated by surgery, chemotherapy and radiotherapy.
      This had resulted in marked abnormalities of the facial skeleton, limited neck
      extension and restricted mouth opening of 1 cm, in part due to dental implants.
      After careful discussion and planning within a multidisciplinary team, the airway
      was optimised by temporary removal of the dental implants. This enabled a
      suspension laryngoscope to be passed, permitting carbon dioxide laser treatment
      to an obstruction at the laryngeal inlet and eliminating the need for a
      tracheostomy.

PMID- 19849680
TI  - Profound hypocalcaemia in a patient being anticoagulated with citrate for
      continuous renal replacement therapy.
AB  - Citrate, as an anticoagulant for continuous renal replacement therapy in
      critically ill patients, has some potential advantages over heparin, including a
      prolonged dialysis filter life and reduced risk of bleeding. The key parameter
      involved in monitoring the adequacy and safety of citrate anticoagulation during
      continuous renal replacement therapy pertains to the ionised and total plasma
      calcium levels. We report a case of severe systemic hypocalcaemia during
      continuous renal replacement therapy with citrate anticoagulation resulting from
      relentless sequestration of calcium due to undiagnosed evolving rhabdomyolysis.
      Although excessive systemic citrate accumulation can also cause hypocalcaemia,
      this complication was not observed in our patient. While an acceptable lower
      limit of ionised calcium remains unknown, severe rhabdomyolysis needs to be
      considered when a patient's ionised calcium levels are not responsive to standard
      calcium replacement therapy during continuous renal replacement therapy using
      citrate anticoagulation in critically ill patients.

PMID- 19849681
TI  - Use of remifentanil as a sedative agent in critically ill adult patients: a meta
      analysis.
AB  - This meta-analysis examined the benefits of using remifentanil as a sedative
      agent in critically ill patients. A total of 11 randomised controlled trials,
      comparing remifentanil with another opioid or hypnotic agent in 1067 critically
      ill adult patients, were identified from the Cochrane controlled trials register
      and EMBASE and MEDLINE databases, and subjected to meta-analysis. Remifentanil
      was associated with a reduction in the time to tracheal extubation after
      cessation of sedation (weighted-mean-difference -2.04 h (95% CI -0.39 to -3.69
      h); p = 0.02). Remifentanil was, however, not associated with a significant
      reduction in mortality (relative risk 1.01 (95% CI 0.67-1.52); p = 0.96),
      duration of mechanical ventilation, length of intensive care unit stay, and risk
      of agitation (relative risk 1.08 (95% CI 0.64-1.82); p = 0.77) when compared to
      an alternative sedative or analgesic agent. The current evidence does not support
      the routine use of remifentanil as a sedative agent in critically ill adult
      patients.

PMID- 19849682
TI  - Unrecognised dural puncture resulting in subdural hygroma and cortical vein
      thrombosis.
AB  - Unrecognised dural punctures are difficult to diagnose early. Failure of
      recognition may lead to sinister consequences. A case of unrecognised dural
      puncture in a young female leading to the development of subdural hygroma and
      cortical vein thrombosis is presented. The dilemma in the diagnosis of headache
      in such patients along with the significance of follow-up of all, including
      attempted, epidurals is also discussed.

PMID- 19849683
TI  - A comparison of the laryngeal mask airway with the facemask and oropharyngeal
      airway for manual ventilation by first responders in children.
AB  - In adults, first responders to a cardiopulmonary arrest provide better
      ventilation using a laryngeal mask airway than a facemask. It is unclear if the
      same is true in children. We investigated this by comparing the ability of 36
      paediatric ward nurses to ventilate the lungs of 99 anaesthetised children (a
      model for cardiopulmonary arrest) using a laryngeal mask airway and using a
      facemask with an oropharyngeal airway. Anteroposterior chest wall displacement
      was measured using an ultrasonic detector. Nurses achieved successful ventilation
      in 74 (75%) of cases with the laryngeal mask airway and 76 (77%) with facemask
      and oropharyngeal airway (p = 0.89). Median (IQR [range]) time to first breath
      was longer for the laryngeal mask airway (48 (39-65 [8-149])) s than the
      facemask/airway (35 (25-53 [14-120]) s; p < 0.0001). In 10 cases (10%) the lungs
      were ventilated using the laryngeal mask airway but not using the
      facemask/oropharyngeal airway. We conclude that ventilation is achieved rapidly
      using a facemask and oropharyngeal airway, and that the laryngeal mask airway may
      represent a useful second line option for first responders.

PMID- 19849684
TI  - Anosmia after general anaesthesia: a case report.
AB  - Although anaesthetic drugs are included among the aetiological factors of
      anosmia, limited reports exist of anosmia induced by general anaesthesia. We
      present the case of a 60-year-old female patient with a 3-month history of
      altered smell and taste immediately after recovery from general anaesthesia for a
      urological operation. The anaesthetic drugs used were fentanyl, propofol and
      sevoflurane. Clinical examination and a computed tomography brain scan did not
      reveal any pathology. Psychophysical testing showed anosmia and normal taste
      function. Imaging studies using single photon emission computed tomography of the
      brain were performed twice: as a baseline examination; and after odour
      stimulation with phenyl ethyl alcohol. Normal brain activity without reaction to
      odorous stimuli suggested peripheral dysfunction or stimuli transmission
      problems. The patient, after four months of olfactory retraining, demonstrated
      significant improvement. The onset of the dysfunction in relation with the
      imaging findings may imply that anaesthetics could induce the olfactory
      dysfunction.

PMID- 19849685
TI  - Tracheal intubation in patients with rigid collar immobilisation of the cervical
      spine: a comparison of Airtraq and LMA CTrach devices.
AB  - The aim of this study was to evaluate the effectiveness of the Airtraq and CTrach
      in lean patients with simulated cervical spine injury after application of a
      rigid cervical collar. Eighty-six consenting adult patients of ASA physical
      status 1 or 2, who required elective tracheal intubation were included in this
      study in a randomised manner. Anaesthesia was induced using 1 microg kg(-1)
      fentanyl, 3 mg kg(-1) propofol and 0.6 mg kg(-1) rocuronium, following which a
      rigid cervical collar was applied. Comparison was then made between tracheal
      intubation techniques using either the AirTraq or CTrach device. The mean (SD)
      time to see the glottis was shorter with the Airtraq than the CTrach (11.9 (6.8)
      vs 37.6 (16.7)s, respectively; p < 0.001). The mean (SD) time taken for tracheal
      intubation was also shorter with the Airtraq than the CTrach (25.6 (13.5) and
      66.3 (29.3)s, respectively; p < 0.001). There was less mucosal damage in the
      Airtraq group (p = 0.008). Our findings demonstrate that use of the Airtraq
      device shortened the tracheal intubation time and reduced the mucosal damage when
      compared with the CTrach in patients who require cervical spine immobilisation.

PMID- 19849686
TI  - Animal model development for the Penn State pediatric ventricular assist device.
AB  - In March 2004, the National Heart, Lung, and Blood Institute awarded five
      contracts to develop devices providing circulatory support for infants and small
      children with congenital and acquired cardiac disease. Since 2004, the team at
      Penn State College of Medicine has developed a pneumatically actuated ventricular
      assist device (VAD) with mechanical tilting disk valves. To date, hemodynamic
      performance, thrombogenesis, and hemolysis have been chronically evaluated in 16
      animals, including 4 pygmy goats and 12 sheep. Major complications, mainly
      respiratory failure, have been encountered and resolved by a multi-disciplinary
      team. Multi-modal analgesia, appropriate antibiotic therapy, and attentive animal
      care have contributed to successful outcomes. Time after implant has ranged from
      0 to 40 days. Most recently, a sheep implanted with Version 3 Infant VAD was
      electively terminated at 35 days postimplant, with no major adverse events. This
      report describes a successful in vivo model for evaluating a pediatric VAD.

PMID- 19849687
TI  - Optimizing the circuit of a pulsatile extracorporeal life support system in terms
      of energy equivalent pressure and surplus hemodynamic energy.
AB  - The nonpulsatile blood flow obtained using standard cardiopulmonary bypass (CPB)
      circuits is still generally considered an acceptable, nonphysiologic compromise
      with few disadvantages. However, numerous reports have concluded that pulsatile
      perfusion during CPB achieves better multiorgan response postoperatively.
      Furthermore, pulsatile flow during CPB has been consistently recommended in
      pediatric and high-risk patients. However, most (80%) of the total hemodynamic
      energy generated by a pulsatile pump is absorbed by the components of the
      extracorporeal circuit and only a small portion of the pulsatile energy is
      delivered to the patient. Therefore, we considered that optimizations of CPB unit
      and extracorporeal life support (ECLS) system circuit components were needed to
      deliver sufficient pulsatile flow. In addition, energy equivalent pressure,
      surplus hemodynamic energy, and total hemodynamic energy, calculated using
      pressure and flow waveforms, were used to evaluate the pulsatilities of pulsatile
      CPB and ECLS systems.

PMID- 19849688
TI  - Evolution of prognostic factors in hepatocellular carcinoma in Japan.
AB  - BACKGROUND: The surveillance of hepatocellular carcinoma (HCC) has become
      prevalent, and the modalities for its treatment have improved. AIM: To understand
      the changes that occur in the characteristics and prognostic factors of HCC with
      time. METHODS: Newly diagnosed HCC patients were divided into two groups;
      patients treated before 31 December 2000 (n = 504), and after 1 January 2001 (n =
      746), and their clinical backgrounds and prognostic factors were analysed.
      RESULTS: The number of patients negative for both Hepatitis B surface antigen
      (HBsAg) and Hepatitis C virus antibody (HCVAb) increased with time (NBNC-HCC).
      The size of HCC decreased in patients who were positive for HBsAg (B-HCC) or
      HCVAb (C-HCC), whereas no difference was observed in NBNC-HCC. The patient
      survival of C-HCC improved; however, no difference was detected for NBNC-HCC. In
      multivariate analysis, low albumin, high aspartate aminotransferase (AST),
      ascites, large tumour size, multiple tumour number and high alpha-fetoprotein
      were risk factors for survival before 2000, whereas the presence of HBsAg was
      additionally selected as a good prognostic factor and AST was excluded after
      2001. CONCLUSIONS: The prognostic factors as well as clinical background of HCC
      changed with time, and the presence of HBsAg was found to be an additional good
      prognostic factor after 2001.

PMID- 19849689
TI  - Dr. Akif Undar named Co-editor of Pediatric Mechanical Support.

PMID- 19849691
TI  - DDT and urogenital malformations in newborn boys in a malarial area.
AB  - OBJECTIVE: To determine the risk of external urogenital birth defects (UGBDs) in
      newborn boys from a malarial area currently sprayed with technical 1,1,1
      trichloro-2,2-bis(4-chlorophenyl) ethane (DDT), as increased fetal oestrogenic or
      anti-androgenic exposure might be involved in the pathogenesis of increased
      prevalence of human male reproductive tract anomalies, and DDT and metabolites
      interact with both these receptors. SUBJECTS AND METHODS: We examined 3310
      newborn baby boys and recorded external UGBDs. RESULTS: Of the newborn boys 10.8%
      (357) had UGBDs; a multivariate logistic model showed that mothers who lived in
      villages sprayed with DDT between 1995 and 2003 had a significantly greater
      chance (33%) of having a baby with a UGBD than mothers whose homes were not
      sprayed (odds ratio 1.33, 95% confidence interval 1.04-1.72). Being a homemaker
      instead of being employed further significantly increased the risk of having a
      baby with a UGBD by 41% (odds ratio 1.41, 1.13-1.77). CONCLUSIONS: Maternal
      exposure to DDT by living in a DDT-sprayed village was associated to having male
      offspring with one or more UGBDs. Monitoring the impact of indoor residual
      spraying on human and environmental health is imperative if DDT is being used,
      especially as climate change raises concerns about the global spread of malaria.
      Integrating adequate indoor residual spraying measures by malarial vector control
      programmes, and increased public awareness to limit personal exposure, are
      crucial components that need to be addressed.

PMID- 19849692
TI  - Haemostatic role and histopathological effects of a new haemostatic agent in a
      rat bladder haemorrhage model: an experimental trial.
AB  - OBJECTIVE: To investigate the haemostatic efficacy and histopathological effects
      of a new haemostatic agent, Ankaferd BloodStopper (ABS; Ankaferd Drug Cosmetic
      Co., Istanbul, Turkey) in a rat bladder haemorrhage model. ABS is a unique
      combination of five plant extracts that has been used in Turkish traditional
      medicine as a haemostatic agent for external traumatic bleeds. MATERIALS AND
      METHODS: In all, 20 male Sprague-Dawley rats were divided into two equal groups.
      In both groups, the mucosa was damaged on the posterior wall (PW) of the bladder.
      The liquid form of ABS was applied to the bleeding area of one group (group 1)
      and 0.9% NaCl to the bleeding area of the other group (group 2, controls). The
      solutions were applied drop by drop with a 2 mL injector until the bleeding
      stopped and the bleeding times recorded. For histopathological examination, two
      tissue samples were taken from all rats in each group; one from the damaged
      mucosa in the PW and one from undamaged mucosa in the lateral wall (LW). Two
      sections were prepared from all samples. One section was stained with
      haematoxylin and eosin (H&E), and the rest was used for immunohistochemical
      staining for fibronectin. RESULTS: The mean bleeding times were 65 s and 147 s
      for groups 1 and 2, respectively (P < 0.001). In the pathological specimens
      stained with H&E, fibrosis and other studied pathological features were similar
      in the LW samples in groups 1 and 2. Similarly, there were no differences between
      the PW samples of groups 1 and 2. In the pathological specimens stained for
      fibronectin, the number of attenuated cells was similar in the LWs of group 1 and
      2 (P = 0.21) as well as in the PWs of each group (P = 0.066). CONCLUSIONS: ABS
      decreased bleeding time and did not increase fibrotic reactions in rat bladder
      tissue.

PMID- 19849693
TI  - Is surveillance of small renal masses safe in the elderly?
AB  - OBJECTIVE: To determine if preoperative variables, including gender, age and
      tumour size, influence the decision for active surveillance of renal masses, as
      due to the increasing detection of incidental renal masses within the ageing
      population there is a need to identify reliable means of selecting patients who
      require therapy. PATIENTS AND METHODS: We retrospectively identified all renal
      masses resected at our institution between 1 December 1999, and 1 October 2005.
      The size of tumour, patient age and gender were compared between those with and
      without malignancy on final pathology. The influence of these variables in
      predicting malignancy, high grade, and high stage were assessed by univariate and
      multivariate analysis using logistic regression models, with a significance level
      of P < 0.05. Subsets were analysed for the groups of patients with tumours of <=
      3 or > 3 cm and those aged <= 75 or > 75 years. RESULTS: Among 466 of 501
      patients with evaluable data, univariate analysis showed that both male gender
      and increasing size positively predicted malignancy (odds ratio 1.13 and 1.40,
      respectively), but age, treated as a continuous variable, did not. On
      multivariate analysis both remained independent predictors of malignancy (odds
      ratio 1.13 and 1.40, respectively). Size was the only independent predictor of
      high-stage and high-grade disease on both univariate and multivariate analysis.
      Among 156 patients with tumours of <= 3 cm, on multivariate analysis, male gender
      was only weakly associated with the risk of malignancy, whereas size remained
      strongly predictive (odds ratio 1.98, P = 0.076; and 2.16, P = 0.015,
      respectively). Neither male gender, size nor age increased the risk of high-stage
      or high-grade disease in this cohort. Patients who were aged > 75 years had a
      greater risk of high-stage disease than those aged < 75 years (odds ratio 2.64, P
      = 0.008). On multivariate analysis, age > 75 years remained an independent
      predictor of malignancy and high-stage, along with size (odds ratio 2.75, P =
      0.014; and 1.35, P < 0.001). CONCLUSIONS: Increased size of tumour increases the
      risk of malignancy and the likelihood of high-stage and high-grade disease. Among
      patients aged > 75 years there was a higher risk of malignancy and high-stage
      disease than in those aged <= 75 years. As such, the decision for observation
      should not be based upon age alone, and should be approached with caution in
      patients aged >75 years, particularly for larger lesions.

PMID- 19849694
TI  - The role of surveillance in the treatment of patients with muscle-invasive
      bladder cancer after chemotherapy.
AB  - OBJECTIVE: To determine the survival of patients at our institution who were
      clinically tumour-free (cT0) on re-staging transurethral resection (TUR) after
      treatment with chemotherapy for muscle-invasive bladder cancer. PATIENTS AND
      METHODS: In all, 55 patients with muscle-invasive, organ-confined transitional
      cell carcinoma of the bladder were treated with TUR followed by systemic
      chemotherapy, over a 10-year period. Patients were separated into two groups,
      those who were clinically T0 and those who showed persistent disease (>cT0) on re
      biopsy after chemotherapy. Overall and disease-specific survival rates were
      calculated for the two groups. The cT0 group was further followed for tumour
      recurrence and clinical outcomes. RESULTS: Thirty-one patients (56%) were
      clinically T0 on TUR after chemotherapy; of these patients, 22 (71%) either died
      from other causes (with no disease recurrence) or are alive and with no evidence
      of disease at a mean follow-up of 53 months. Twenty of the 31 patients (65%) have
      retained their bladder with no evidence of cancer recurrence at a mean follow-up
      of 46 months. Disease-free status (cT0) at the time of TUR after chemotherapy was
      associated with significantly higher overall and cancer-specific survival (hazard
      ratio 3.40, P = 0.003; and 8.63, P = 0.001, respectively). CONCLUSION: Previous
      studies suggest that surveillance can be a reasonable option for patients with
      muscle-invasive transitional cell carcinoma of the bladder who show no evidence
      of disease on TUR after chemotherapy. Patients with persistent bladder cancer on
      re-biopsy after chemotherapy tend to fare poorly even with immediate cystectomy.

PMID- 19849695
TI  - A randomized controlled trial in children with eczema: nurse practitioner vs.
      dermatologist.
AB  - Background We hypothesized that a nurse practitioner would improve the quality of
      life of a child with eczema more than a dermatologist because of a structured
      intervention and more consultation time. Objectives To compare the level of care
      by nurse practitioners with that by dermatologists in children with eczema.
      Methods New referrals aged < or = 16 years with a diagnosis of eczema were
      recruited. In a randomized, parallel-group study with a follow-up period of 1
      year, 160 participants were randomized either to conventional care from a
      dermatologist or to care from a nurse practitioner. The primary outcome measure
      was change in quality of life at 12 months, as assessed by the Infants'
      Dermatitis Quality of Life Index (IDQOL) for children aged < or = 4 years, and by
      the illustrated version of the Children's Dermatology Life Quality Index (CDLQI)
      for children aged 4-16 years. Secondary outcomes were changes in IDQOL and CDLQI
      at 4 and 8 months, family impact of childhood atopic dermatitis (Dermatitis
      Family Impact Questionnaire, DFI), eczema severity (objective SCORAD) and patient
      satisfaction (Client Satisfaction Questionnaire-8, CSQ-8) at 4, 8 and 12 months.
      Results The mean IDQOL in the dermatologist group improved significantly from
      11.6 [SD 8.1; 95% confidence interval (CI) 9.0-14.2] at the baseline to 5.6 (SD
      3.9; 95% CI 4.3-7.0) at 12 months with a mean change from the baseline of -6.5
      (SD 6.6; 95% CI -14.2 to -8.9; P < 0.001). The mean IDQOL in the nurse
      practitioner group improved significantly from 10.7 (SD 4.9; 95% CI 9.1-12.3) at
      baseline to 5.7 (SD 5.4; 95% CI 4.0-7.5) at 12 months with a mean change from the
      baseline of -4.9 (SD 5.5; 95% CI -6.8 to -3.0; P < 0.001). The between-groups
      difference was (-)1.7 (95% CI -4.6 to 1.2; P = 0.26). The mean CDLQI in the
      dermatologist group improved significantly from 12.1 (SD 6.3; 95% CI 9.9-14.2) at
      baseline to 5.6 (SD 4.2; 95% CI 4.2-7.1) at 12 months with a mean change from the
      baseline of -5.9 (SD 6.0; 95% CI -8.0 to -3.9; P < 0.001). The mean CDLQI in the
      nurse practitioner group improved significantly from 10.0 (SD 4.4; 95% CI 8.5
      11.4) at the baseline to 4.9 (SD 3.5; 95% CI 3.7-6.1) at 12 months with a mean
      change from the baseline of -5.2 (SD 4.0; 95% CI -6.6 to -3.8; P < 0.001). The
      between-groups difference was (-)0.7 (95% CI -3.3 to 1.7; P = 0.55). The between
      groups comparison was not significant for the IDQOL and the CDLQI at baseline or
      4, 8 and 12 months. Both treatment groups showed significant improvement in DFI
      and objective SCORAD at 12 months. The between-groups comparison was not
      significant at baseline or 4, 8 and 12 months. Significantly higher satisfaction
      levels were observed at 4, 8 and 12 months in the nurse practitioner group.
      Conclusions The level of care provided by a nurse practitioner in terms of the
      improvement in the eczema severity and the quality of life outcomes was
      comparable with that provided by a dermatologist. In addition, the parents were
      more satisfied with the care that was provided by a nurse practitioner.

PMID- 19849696
TI  - Improvement in skin wrinkles from the use of photostable retinyl retinoate: a
      randomized controlled trial.
AB  - BACKGROUND: Photoaged skin can be treated with retinoids, which are natural and
      synthetic vitamin A derivatives. However, these are photounstable and can cause
      skin irritation, which is a major limitation in their use in general cosmetics.
      Retinyl retinoate, which is an ester of all-trans retinoic acid (RA) and all
      trans retinol, has reduced toxicity due to blocking of the carboxyl end group of
      RA and higher skin regeneration activity than retinol. OBJECTIVES: To assess the
      efficacy of a photostable retinyl retinoate in treating women over 30 years old
      with periorbital wrinkles. METHODS: We conducted two clinical studies with a
      total of 46 Korean women with periorbital wrinkles, who were not pregnant,
      nursing or undergoing any concurrent therapy. In the first clinical study, the
      efficacy of retinyl retinoate was compared with placebo. Twenty-four patients
      completed a 12-week trial of 0.06% retinyl retinoate applied twice daily to one
      side of the face and a placebo applied to the other side. In the second clinical
      study, the efficacy of retinyl retinoate was compared with retinol. Twenty-two
      patients completed an 8-week trial of 0.06% retinyl retinoate applied twice daily
      to one side of the face and 0.075% retinol applied to the other side. Efficacy
      was based on a global photodamage score, photographs, and image analysis using
      replicas and visiometer analysis (Skin-Visiometer SV 600; Courage & Khazaka,
      Cologne, Germany) every 4 weeks. The standard wrinkle and roughness parameters
      used in assessing skin by visiometer were calculated and statistically analysed.
      RESULTS: The retinyl retinoate-treated wrinkles improved compared with wrinkles
      treated with placebo or retinol, as assessed by both the investigators and the
      subjects. Also, skin replica analysis indicated significant improvements in
      retinyl retinoate-treated skin in both studies, especially in average roughness.
      CONCLUSIONS: Retinyl retinoate applied twice daily was significantly more
      effective than a placebo or retinol in treating periorbital wrinkles.
      Importantly, no severe side-effects were observed.

PMID- 19849697
TI  - Viral DNA detection and RAS mutations in actinic keratosis and nonmelanoma skin
      cancers.
AB  - BACKGROUND: Actinic keratosis (AK) is a well-established precancerous skin lesion
      that has the potential to progress to squamous cell carcinoma (SCC). Basal cell
      carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely
      metastasizes. A number of viruses have been proposed to play a role in the
      development of nonmelanoma skin cancers (NMSC), but the most plausible evidence
      to date suggests that cutaneous human papillomavirus (HPV) is the key instigating
      factor. OBJECTIVES: To evaluate the prevalence of HPV, cytomegalovirus (CMV),
      herpes simplex virus (HSV) and Epstein-Barr virus (EBV) and investigate their
      relationship with the presence of RAS gene mutations in cutaneous lesions
      obtained from nonimmunosuppressed patients. METHODS: HPV, CMV, HSV and EBV
      detection was performed using polymerase chain reaction (PCR) in skin biopsies
      (26 AK, 12 SCC and 15 BCC samples) that were collected from immunocompetent
      patients. The RAS mutation incidence was also investigated in all cutaneous
      lesions by use of PCR/restriction fragment length polymorphism and direct DNA
      sequencing. RESULTS: Seventeen out of 53 (32%) skin lesions were found to be
      positive for HPV DNA. The highest incidences of HPV infection were five of 15
      (33%) in BCC and four of 12 (33%) in SCC specimens. The HPV incidence was eight
      of 26 (31%) in AK and eight of 53 (15%) in normal skin tissue. Twelve out of 53
      (23%) skin lesions were CMV-positive. The highest incidence of CMV infection was
      six of 15 (40%), observed in BCC specimens. The CMV incidence was two of 26 (8%)
      in AK and four of 12 (33%) in SCC. No normal skin biopsy was found to be positive
      for CMV. All cutaneous samples were negative for HSV and EBV DNA, as assessed by
      our PCR-based assays. Only three samples, one AK (4%), one BCC (6%) and one SCC
      (8%), were found to carry a G>T transversion at the second position of HRAS codon
      12. Both HRAS mutant SCC and BCC biopsies were HPV- and CMV-positive, as well.
      CONCLUSIONS: HPV DNA is detected in NMSC, AK and normal skin biopsies. Our
      results also indicate that CMV is involved in NMSC at higher levels than in
      premalignant lesions, whereas the virus was not detected in normal skin biopsies.
      HSV and EBV do not appear to be involved in the pathogenesis of cutaneous
      lesions. Moreover, we suggest that the HRAS codon 12 mutation is not a very
      common event in AK or NMSC. Finally, both viral infection and HRAS activation
      appear to represent independent factors in the aetiology of NMSC, samples of
      which were obtained from immunocompetent patients.

PMID- 19849698
TI  - Late-onset of IgE sensitization to microbial allergens in young children with
      atopic dermatitis.
AB  - Background A significant proportion of young children with atopic dermatitis (AD)
      is sensitized to microbial allergens, which play a potential role in the
      pathogenesis of AD inflammation. Objective To study the timing of IgE
      sensitization to microbial allergens including staphylococcal superantigens,
      Malassezia species and Candida albicans in young children with AD. Method
      Specific IgE antibodies to staphylococcal superantigens, Malassezia species, C.
      albicans and control inhalant/food allergens were measured in 53 young children
      with mild to moderate AD. The presence of IgE sensitization relative to age (> or
      = 3 years vs. < 3 years) was analysed by logistic regressions. Results IgE
      sensitization to the staphylococcal superantigen group, Malassezia species and C.
      albicans was significantly associated with older age in children with AD [P =
      0.02, odds ratio (OR) 4.9; P = 0.02, OR 4.7; and P = 0.05, OR 4.0, respectively].
      Conclusion IgE sensitization to microbial allergens is associated with an older
      age group in young children with mild to moderate AD.

PMID- 19849699
TI  - The effect of in vivo growth hormone treatment on blood gene expression in adults
      with growth hormone deficiency reveals potential biomarkers to monitor growth
      hormone therapy.
AB  - OBJECTIVE: Growth hormone (GH) replacement therapy is presently utilized in the
      treatment of adult GH deficiency (AGHD). Adult responses to GH treatment are
      highly variable and, apart from measurement of IGF-I, few tools are currently
      available for monitoring GH treatment progress. As GH receptors are expressed in
      certain blood cell types, changes in gene expression in peripheral blood can
      reflect perturbations induced as a result of GH therapy. DESIGN/PATIENTS: We have
      carried out a pilot study to identify GH-responsive genes in blood, and have
      assessed the utility of GH-responsive genes in monitoring GH therapy in AGHD.
      Blood was collected from ten women diagnosed with AGHD syndrome both before and 4
      weeks after initiation of GH substitutive therapy. RNA was extracted from
      peripheral blood mononuclear cells (PBMCs) and changes in response to GH were
      detected using microarray-based gene analysis. RESULTS: All patients responded to
      GH replacement therapy, with serum levels of IGF-I increasing by an average of
      307% (P = 0.0003) while IGFBP-3 increased by an average of 182% (P = 0.0002).
      Serum levels of triglycerides, LDL-C, HDL-C, APOA1 or APOB did not change after 1
      month of GH treatment. By contrast, we detected an increase in Lp(a) serum levels
      (P = 0.0149). Using a stringent selection cutoff of P <or= 0.05, paired analysis
      identified a set of transcripts that correlated with GH administration. We
      applied the multivariate statistical technique PLS-DA to the changes in gene
      expression, demonstrating their utility in differentiating untreated patients and
      those undergoing GH replacement therapy. CONCLUSION: This study shows that GH
      dependent effects on gene expression in PBMCs can be detected by microarray-based
      gene analysis, and our results establish a foundation for the further exploration
      of peripheral blood as a surrogate to detect exposure to GH therapy.

PMID- 19849701
TI  - Abstracts of the 41st Annual Scientific Congress, the Royal Australian and New
      Zealand College of Ophthalmologists. November 14-18, 2009. Brisbane, Queensland,
      Australia.

PMID- 19849700
TI  - MicroRNA signature in massive macronodular adrenocortical disease and
      implications for adrenocortical tumourigenesis.
AB  - PURPOSE: Massive macronodular adrenocortical disease (MMAD) may be caused by
      aberrant microRNA expression. To determine the microRNA profile in MMAD and
      identify putative microRNA-gene target pairs involved in adrenal tumourigenesis.
      EXPERIMENTAL DESIGN: We performed microRNA microarray analysis in 10 patients
      with ACTH-independent Cushing syndrome caused by MMAD (ages 39-60 years) and four
      normal adrenal cortex samples were used as controls. Microarray data were
      validated by real-time polymerase chain reaction (qRT-PCR). Identification of
      potential microRNA-gene target pairs implicated in MMAD pathogenesis has been
      performed by integrating our microRNA data with previously obtained cDNA
      microarray data. Experimental validation of specific microRNA gene targets was
      performed by transfection experiments and luciferase assay. RESULTS: A total of
      37 microRNAs were differentially expressed between MMAD and normal tissues; 16
      microRNAs were down-regulated, including miR-200b and miR-203, whereas 21
      microRNAs were up-regulated, miR-210 and miR-484 among them. Comparison of
      microRNA data with different clinicopathological parameters revealed miR-130a and
      miR-382 as putative diagnostic MMAD markers. Interestingly, we detected miR-200b
      targeting directly Matrin 3 (MATR3) expression in an adrenocortical cancer cell
      line (H295R). CONCLUSIONS: MicroRNAs appear to have distinct regulatory effects
      in MMAD, including an association with clinical presentation and severity of the
      disease, expressed by the degree of hypercortisolism. This is the first
      investigation of microRNAs in MMAD, a disease with complex pathogenesis; the data
      indicate that specific microRNAs such as miR-200b may play a significant role in
      MMAD formation and/or progression.

PMID- 19849703
TI  - Incidence and management of biliary complications after adult-to-adult living
      donor liver transplantation.
AB  - BACKGROUND: There are few detailed reports of biliary complications in a large
      adult living donor liver transplantation (LDLT) series. PATIENT AND METHODS:
      Biliary complications, treatment modalities, and outcomes in these patients were
      retrospectively analyzed in 310 adult LDLT. RESULTS: One patient underwent
      retransplantation. Duct-to-duct anastomosis was primarily performed in 223
      patients (72%). During the observation period (median 43 months), biliary
      complications were observed in 111 patients (36%); 53 patients (17%) had bile
      leakage, 70 patients (23%) had bile duct stenosis, and 12 patients (4%) had bile
      leakage followed by stenosis. A biliary anastomotic stent tube was placed in 266
      patients (86%) at the time of transplantation. Univariate analysis of various
      clinical factors revealed duct-to-duct anastomosis as the single significant risk
      factor (p=0.009) for biliary complications. The three-yr and five-yr overall
      patient survival rates were 88% and 85% in those with biliary complications, and
      85% and 83%, respectively, in those without biliary complications (p=0.59).
      CONCLUSION: Biliary complications are a major cause of morbidity following LDLT.
      Duct-to-duct anastomosis carried a higher risk for bile duct stenosis. With
      appropriate management, however, there was little influence on overall survival.

PMID- 19849704
TI  - Bronchiolitis obliterans following hematopoietic stem cell transplantation: a
      clinical update.
AB  - Hematopoietic stem cell transplantation (HSCT) is an established treatment for a
      variety of malignant and non-malignant conditions. Pulmonary complications,
      infectious and non-infectious, are a major cause of morbidity and mortality in
      these patients. The recent advances in prophylaxis and treatment of infectious
      complications increased the significance of late non-infectious pulmonary
      conditions. Currently, bronchiolitis obliterans is one of the most challenging
      pulmonary complications facing clinicians who are taking care of HSCT recipients.
      This report provides a clinical update of the incidence, risk factors,
      pathogenesis, clinical characteristics, and management of bronchiolitis
      obliterans following HSCT.

PMID- 19849705
TI  - Injection drug use before and after liver transplantation: a retrospective
      multicenter analysis on incidence and outcome.
AB  - BACKGROUND AND AIMS: Injecting drug use (IDU) before and after liver
      transplantation (LT) is poorly described. The aim of this study was to quantify
      relapse and survival in this population and to describe the causes of mortality
      after LT. METHODS: Past injection drug users were identified from the LT listing
      protocols from four centers in Switzerland and France. Data on survival and
      relapse were collected and used for uni- and multivariate analysis. RESULTS:
      Between 1988 and 2006, we identified 59 patients with a past history of IDU. The
      mean age at transplantation was 42.4 yr and the majority of patients were men
      (84.7%). The indication for LT was for the vast majority viral cirrhosis
      accounting for 91.5% of cases, while alcoholic cirrhosis was 5.1%. There were
      16.9% of patients who had a substitution therapy before and 6.8% who continued
      after LT. Two patients (3.4%) relapsed into IDU after LT and died at 18 and 41
      months. The mean follow-up was 51 months. Overall survival was 84%, 66%, and 61%
      at 1, 5, and 10 yr after transplantation. CONCLUSIONS: Documented IDU was rare in
      liver transplanted patients. Past IDU was not associated with poorer survival
      after LT, and relapse after LT occurred in 3.4%.

PMID- 19849706
TI  - The risk of cross-contamination during rigid sigmoidoscopy.

PMID- 19849707
TI  - The role of transcranial magnetic stimulation in the characterization of
      congenital hemiparesis.

PMID- 19849708
TI  - Evolutionary history and distance dependence control survival of dipterocarp
      seedlings.
AB  - One important hypothesis to explain tree-species coexistence in tropical forests
      suggests that increased attack by natural enemies near conspecific trees gives
      locally rare species a competitive advantage. Host ranges of natural enemies
      generally encompass several closely related plant taxa suggesting that seedlings
      should also do poorly around adults of closely related species. We investigated
      the effects of adult Parashorea malaanonan on seedling survival in a Bornean rain
      forest. Survival of P. malaanonan seedlings was highest at intermediate distances
      from parent trees while heterospecific seedlings were unaffected by distance.
      Leaf herbivores did not drive this relationship. Survival of seedlings was lowest
      for P. malaanonan, and increased with phylogenetic dissimilarity from this
      species, suggesting that survival of close relatives of common species is
      reduced. This study suggests that distance dependence contributes to species
      coexistence and highlights the need for further investigation into the role of
      shared plant enemies in community dynamics.

PMID- 19849709
TI  - Phenotypic divergence during the invasion of Phyla canescens in Australia and
      France: evidence for selection-driven evolution.
AB  - Rapid adaptive evolution has been advocated as a mechanism that promotes
      invasion. Demonstrating adaptive evolution in invasive species requires rigorous
      analysis of phenotypic shifts driven by selection. Here, we document selection
      driven evolution of Phyla canescens, an Argentine weed, in two invaded regions
      (Australia and France). Invasive populations possessed similar or higher
      diversity than native populations, and displayed mixed lineages from different
      sources, suggesting that genetic bottlenecks in both countries might have been
      alleviated by multiple introductions. Compared to native populations, Australian
      populations displayed more investment in sexual reproduction, whereas French
      populations possessed enhanced vegetative reproduction and growth. We partitioned
      evolutionary forces (selection vs. stochastic events) using two independent
      methods. Results of both analyses suggest that the pattern of molecular and
      phenotypic variability among regions was consistent with selection-driven
      evolution, rather than stochastic events. Our findings indicate that selection
      has shaped the evolution of P. canescens in two different invaded regions.

PMID- 19849710
TI  - Weak population regulation in ecological time series.
AB  - How strongly natural populations are regulated has a long history of debate in
      ecology. Here, we discuss concepts of population regulation appropriate for
      stochastic population dynamics. We then analyse two large collections of data
      sets with autoregressive-moving average (ARMA) models, using model selection
      techniques to find best-fitting models. We estimated two metrics of population
      regulation: the characteristic return rate of populations to stationarity and the
      variability of the stationary distribution (the long-term distribution of
      population abundance). Empirically, longer time series were more likely to show
      weakly regulated population dynamics. For data sets of length > or = 20, more
      than 35% had characteristic return times > 6 years, and more than 29% had
      stationary distributions whose coefficients of variation were more than two times
      greater than would be the case if they were maximally regulated. These results
      suggest that many natural populations are weakly regulated.

PMID- 19849711
TI  - Biodiversity in a complex world: consolidation and progress in functional
      biodiversity research.
AB  - The global decline of biodiversity caused by human domination of ecosystems
      worldwide is supposed to alter important process rates and state variables in
      these ecosystems. However, there is considerable debate on the prevalence and
      importance of biodiversity effects on ecosystem function (BDEF). Here, we argue
      that much of the debate stems from two major shortcomings. First, most studies do
      not directly link the traits leading to increased or decreased function to the
      traits needed for species coexistence and dominance. We argue that implementing a
      trait-based approach and broadening the perception of diversity to include trait
      dissimilarity or trait divergence will result in more realistic predictions on
      the consequences of altered biodiversity. Second, the empirical and theoretical
      studies do not reflect the complexity of natural ecosystems, which makes it
      difficult to transfer the results to natural situations of species loss. We
      review how different aspects of complexity (trophic structure,
      multifunctionality, spatial or temporal heterogeneity, and spatial population
      dynamics) alter our perception of BDEF. We propose future research avenues
      concisely testing whether acknowledging this complexity will strengthen the
      observed biodiversity effects. Finally, we propose that a major future task is to
      disentangle biodiversity effects on ecosystem function from direct changes in
      function due to human alterations of abiotic constraints.

PMID- 19849712
TI  - Upregulation of cathepsin S in psoriatic keratinocytes.
AB  - Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class
      II-mediated antigen presentation and extracellular matrix degradation.
      Disturbance of the expression or metabolism of this protease is a concomitant
      feature of several diseases. Given this importance we studied the localization
      and regulation of CATS expression in normal and pathological human/mouse skin. In
      normal human skin CATS-immunostaining is mainly present in the dermis and is
      localized in macrophages, Langerhans, T- and endothelial cells, but absent in
      keratinocytes. In all analyzed pathological skin biopsies, i.e. atopic
      dermatitis, actinic keratosis and psoriasis, CATS staining is strongly increased
      in the dermis. But only in psoriasis, CATS-immunostaining is also detectable in
      keratinocytes. We show that cocultivation with T-cells as well as treatment with
      cytokines can trigger expression and secretion of CATS, which is involved in MHC
      II processing in keratinocytes. Our data provide first evidence that CATS
      expression (i) is selectively induced in psoriatic keratinocytes, (ii) is
      triggered by T-cells and (iii) might be involved in keratinocytic MHC class II
      expression, the processing of the MHC class II-associated invariant chain and
      remodeling of the extracellular matrix. This paper expands our knowledge on the
      important role of keratinocytes in dermatological disease.

PMID- 19849713
TI  - Dysregulation of CD36 upon TLR-2 stimulation in monocytes from patients with
      atopic dermatitis and the TLR2 R753Q polymorphism.
AB  - BACKGROUND: The cutaneous colonization with Staphylococcus aureus represents a
      potent trigger factor of atopic dermatitis. Toll-like receptor (TLR)-2 and CD36
      have been shown to play a pivotal role in the internalization of staphylococcal
      components. AIMS: To investigate the impact of TLR-2 ligands on cell surface
      protein expression in monocytes from wild type (WT) AD patients and TLR-2 R753Q
      polymorph AD patients. RESULTS: CD36 expression was significantly less
      downregulated in TLR-2 polymorph AD patients compared to wild type AD patients
      upon stimulation with peptidoglycan (PGN) and lipoteichoic acid (LTA) and
      compared to healthy controls upon stimulation with PGN. Expression of CD86 was
      higher upon N-palmitoyl-S-[2,3-bis(palmitoyl)-(2RS)-propyl]-(R)cysteinyl-alanyl
      glycine (Pam3Cys) stimulation in TLR-2 R753Q polymorph AD patients compared to
      wild type AD patients. Expression of CD80 and CD54 were unaffected. CONCLUSION:
      The differences in CD36 expression in TLR-2 polymorph AD patients compared to
      wild type AD patients and healthy controls may be associated with an enhanced
      susceptibility to skin infections with S. aureus.

PMID- 19849714
TI  - Influence of narrowband UVB phototherapy on vitamin D and folate status.
AB  - BACKGROUND: A variety of studies have shown beneficial effects of different types
      of phototherapy in skin disorders. Such therapy leads to enhanced cutaneous
      vitamin D synthesis, which may be one of the mechanisms of action. Furthermore,
      another nutrient, folate, can probably also be influenced by UV radiation.
      OBJECTIVE: The aim of our study was to investigate the influence of low-dose
      narrowband UVB (nUVB) phototherapy of patients with psoriasis, atopic eczema and
      other skin disorders on serum levels of 25(OH) vitamin D (the serum marker for
      vitamin D status) and on serum and erythrocyte-folate. METHODS: 25(OH) vitamin D
      (25(OH)D), serum and erythrocyte-folate levels were measured before and after low
      dose nUVB (TL-01 tubes) phototherapy of these patients. The spectrum of the TL-01
      tube was compared with the solar spectrum, and the efficiency spectra of vitamin
      D photosynthesis were calculated. RESULTS: For patients with a high initial
      25(OH)D serum level (> 80 nmol/l), no significant (P = 0.36) increase in 25(OH)D
      levels was seen, in contrast to patients with a low initial level (< 80 nmol/l)
      where a significant increase (P < 0.001) was observed. The increase was 30-60%,
      depending on the UVB dose (2.35-13.4 J/cm(2)). No significant nUVB-effect was
      found on the erythrocyte and serum-folate level. CONCLUSION: Low-dose nUVB
      treatment gives a significant increase (P < 0.001) of the vitamin D status in
      persons with low initial levels of 25(OH)D, but no effect on the folate level.

PMID- 19849715
TI  - Mouse models for melanoma: a personal perspective.
AB  - Complex biological processes often require in vivo analysis, and many important
      research advances have been made using mice as a model for the study of various
      biological systems. Cutaneous melanomas are tumors originating from skin
      melanocytes, which are present in hair follicles, and interfollicular epidermal
      and dermal layers. Until recently, mouse melanoma models were largely based on
      transplantation models, i.e. transplantation of either syngeneic or xenogeneic
      melanoma cells into wild type or genetically modified animals. More recently,
      however, the use of novel technologies specifically modifying the genome allows
      for the generation of mouse strains, which may develop spontaneous melanoma.
      Nevertheless, it should be kept in mind that animal models provide only an
      approximation of reality in humans. In this review, we will discuss a
      representative selection of currently available transplantation and transgenic
      melanoma models; despite the fact that this selection will be biased by personal
      experience, we are confident to demonstrate how the use of mouse melanoma models
      facilitates translational research in several biomedical disciplines.

PMID- 19849716
TI  - Effect of topical application and intraperitoneal injection of oregonin on atopic
      dermatitis in NC/Nga mice.
AB  - The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus
      japonica Steudel that grows natively in Korea, has been known to exert
      antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory
      effects. The antioxidative effect of ORE was observed on the superoxide and 1,1
      diphenyl-2-picrylhydrazyl radical, as well as on the expression of inducible
      nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated RAW264.7
      macrophages. The statistically significant inhibitory action of ORE against
      production of cytokines induced by bacterial products or by interleukin (IL)
      1beta, free radicals and nitrogen species, and a corresponding increase in
      cellular calcium concentration because of ORE were confirmed in bone marrow and
      spleen dendritic cells that are known to play important functions in the
      development and advancement of atopic dermatitis (AD). It was thus expected that
      ORE would exert a beneficial effect in the treatment of AD. A study on the
      pharmaceutical benefits of ORE against AD has not yet been conducted in vivo. We
      therefore used an in vivo AD animal model, namely the NC/Nga mice, and by
      applying ORE onto the animals through skin application as well as intraperitoneal
      injection, we attempted to evaluate the benefits of ORE in this system.
      Evaluation of ORE was conducted by following the SCORE method to score the
      effect, as well as by measuring the Th2 cytokines IL-4, IL-5 and IL-13 levels
      from serum and lymphocytes, and IgE and eosinophil levels from serum.
      Additionally, the expression of mRNA and protein levels was estimated using real
      time polymerase chain reaction and Western blotting analysis. The following
      categories of clinical evaluation, Th2 cytokines IL-4, IL-5 and IL-13 values,
      serum IgE levels, serum eosinophil levels, and mRNA and protein expression levels
      of iNOS and COX-2, were evaluated from topical application and intraperitoneal
      injection groups of ORE. The effects of ORE on AD in NC/Nga mice were confirmed
      as being similar to the positive control group, while a significant difference
      with the negative control group was observed. The results presented in this
      report suggest that ORE might be beneficial in the treatment of AD.

PMID- 19849717
TI  - Saccharomyces cerevisiae plasma membrane nutrient sensors and their role in PKA
      signaling.
AB  - The ability to elicit a fast intracellular signal leading to an adaptive response
      is crucial for the survival of microorganisms in response to changing
      environmental conditions. Therefore, in order to sense changes in nutrient
      availability, the yeast Saccharomyces cerevisiae has evolved three different
      classes of nutrient-sensing proteins acting at the plasma membrane: G protein
      coupled receptors or classical receptor proteins, which detect the presence of
      certain nutrients and activate signal transduction in association with a G
      protein; nontransporting transceptors, i.e. nutrient carrier homologues with only
      a receptor function, previously called nutrient sensors; and transporting
      transceptors, i.e. active nutrient carriers that combine the functions of a
      nutrient transporter and receptor. Here, we provide an updated overview of the
      proteins involved in sensing nutrients for rapid activation of the protein kinase
      A pathway, which belong to the first and the third category, and we also provide
      a comparison with the best-known examples of the second category, the
      nontransporting transceptors, which control the expression of the regular
      transporters for the nutrient sensed by these proteins.

PMID- 19849718
TI  - High-throughput screening of Hansenula polymorpha clones in the batch compared
      with the controlled-release fed-batch mode on a small scale.
AB  - Most large-scale production processes in biotechnology are performed in fed-batch
      operational mode. In contrast, the screenings for microbial production strains
      are run in batch mode, which results in the microorganisms being subjected to
      different physiological conditions. This significantly affects strain selection.
      To demonstrate differences in ranking during strain selection depending on the
      operational mode, screenings were performed in batch and fed-batch modes. Two
      model populations of the methylotrophic yeast Hansenula polymorpha RB11 with
      vector pC10-FMD (P(FMD)-GFP) (220 clones) and vector pC10-MOX (P(MOX)-GFP) (224
      clones) were applied. For fed-batch cultivations in deep-well microtiter plates,
      a controlled-release system made of silicone elastomer discs containing glucose
      was used. Three experimental set-ups were investigated: batch cultivation with
      (1) glucose as a substrate, which catabolite represses product formation, and (2)
      glycerol as a carbon source, which is partially repressing, respectively, and (3)
      fed-batch cultivation with glucose as a limiting substrate using the controlled
      release system. These three experimental set-ups showed significant variations in
      green fluorescent protein (GFP) yield. Interestingly, screenings in fed-batch
      mode with glucose as a substrate resulted in the selection of yeast strains
      different from those cultivated in batch mode with glycerol or glucose.
      Ultimately, fed-batch screening is considerably better than screening in batch
      mode for fed-batch production processes with glucose as a carbon source.

PMID- 19849719
TI  - Mammalian COP9 signalosome.
AB  - The COP9 signalosome (CSN) complex is highly conserved from yeast to human.
      Although the plant CSN was first identified as a negative regulator of
      photomorphogenesis, the mammalian CSN is linked to different biological responses
      such as checkpoint control, signal transduction, development and the cell cycle.
      Frequent over-expression of the CSN subunit in a variety of human cancers
      suggests its involvement in cell transformation and tumorigenesis. The best-known
      biochemical function associated with the CSN is the control of protein stability
      via the ubiquitin-proteasome system through regulation of cullin-RING-E3
      ubiquitin ligase activity by deneddylation, by controlling the activity of COP1
      E3 ligase, or by counteracting ubiquitin-mediated degradation through a CSN
      associated deubiquitinating enzyme. In addition to affecting the stability of
      transcription factors, the CSN may regulate gene transcription by directly
      associating with chromatin. This review summarizes recent findings and discusses
      the physiological role and the cellular function of the mammalian CSN in terms of
      the regulation of cell proliferation.

PMID- 19849720
TI  - Needle-free subcutaneous sumatriptan (Sumavel DosePro): bioequivalence and ease
      of use.
AB  - BACKGROUND: Subcutaneous (s.c.) injection of sumatriptan is currently associated
      with needle aversion in some patients, and sharps disposal issues. OBJECTIVES: To
      investigate whether a needle-free system can deliver s.c. sumatriptan. If so, to
      examine whether needle-free administration is bioequivalent to a 26-gauge needle
      based auto-injector. Lastly, to assess the needle-free system for clinical
      acceptability and ease of use during migraine attacks. METHODS: Two clinical
      trials. Study A: Pharmacokinetics and bioequivalence was studied in normal adult
      volunteers (n = 57 total), directly comparing needle-free (Sumavel DosePro) with
      needle-based (Imitrex STATdose System) administration of 6 mg s.c. sumatriptan.
      An incomplete, randomized, partial factorial, crossover design was used. Each
      subject received 2 administrations of each product, at 2 of the 3 anatomical
      sites (abdomen, thigh or arm). There were appropriate "washout" periods between
      each. Pharmacokinetic sampling was at standard time points, and tests for
      bioequivalence then followed. Study B: The term "ease of use" was used for
      clinical acceptability and utility of the needle-free system when it was assessed
      among 52 outpatients treating migraine attacks. Instructional materials were used
      as would be provided after ordinary prescription. The primary endpoint was
      successful use of the needle-free system to administer sumatriptan at the first
      attempt, including appropriate injection site selection. Second and subsequent
      uses of the needle-free system were also documented. RESULTS: For administration
      sites in the thigh and the abdomen, but not the arm, the needle-free and needle
      based systems were bioequivalent (for all pharmacokinetic endpoints the mean
      ratios between the 2 devices were always between 90.1% and 115%). Among
      outpatients treating a migraine attack with the needle-free system, 51 of 52 on
      first attempt used the needle-free system successfully when treating a migraine
      attack. CONCLUSIONS: Sumavel DosePro needle-free delivery system is a new
      presentation of s.c. sumatriptan that delivers drug effectively, is bioequivalent
      to the existing needle auto-injector when used at the thigh or abdomen, and is
      easy to use.

PMID- 19849721
TI  - A coleopteran triosephosphate isomerase: X-ray structure and phylogenetic impact
      of insect sequences.
AB  - A coleopteran triosephosphate isomerase (TIM) from Tenebrio molitor (yellow
      mealworm beetle) was recombinantly expressed in Escherichia coli and
      characterized with respect to thermal stability, kinetic parameters and
      oligomeric state. The enzyme was successfully crystallized and the structure
      determined by X-ray analysis to 2.0 A resolution. This is the first example of an
      invertebrate TIM. We compare structural features with known structures of TIMs
      from microorganisms, plants and vertebrates, and discuss the utility of the
      Tenebrio TIM sequence, together with several newly sequenced insect TIMs, for
      molecular phylogenetic analysis.

PMID- 19849722
TI  - Abundant nuclear copies of mitochondrial origin (NUMTs) in the Aedes aegypti
      genome.
AB  - A portion of the Aedes aegypti mitochondrial NADH dehydrogenase subunit 4 gene
      (ND4) was amplified using PCR with a 42 degrees C annealing temperature.
      Amplified fragments from individual mosquitoes were similar to ND4 but contained
      multiple segregating sites. We suspected that nuclear copies of mitochondrial
      origin (NUMTs) exist in the Ae. aegypti genome. A BlastN search in VectorBase
      with the entire Ae. aegypti mitochondrial genome identified 233 NUMTs comprising
      110 178 bp in 145 supercontigs. At a density of 0.080 bp/kb, this represents the
      second highest density of NUMTs in an insect genome and the highest in Diptera.
      Analyses of flanking sequences suggested that Ae. aegypti NUMTs arise through
      mtDNA leakage from damaged mitochondria followed by breakage and nonhomologous
      recombination, rather than through duplicative processes such as transposition or
      molecular drive.

PMID- 19849723
TI  - Pharmacological characterization of cis-nitromethylene neonicotinoids in relation
      to imidacloprid binding sites in the brown planthopper, Nilaparvata lugens.
AB  - Neonicotinoid insecticides, such as imidacloprid, are selective agonists of the
      insect nicotinic acetylcholine receptors (nAChRs) and extensively used in areas
      of crop protection and animal health to control a variety of insect pest species.
      Here we describe that two cis-nitromethylene neonicotinoids (IPPA152002 and
      IPPA152004), recently synthesized in our laboratory, discriminated between the
      high and low affinity imidacloprid binding sites in the brown planthopper,
      Nilaparvata lugens, a major insect pest of rice crops in many parts of Asia.
      [(3)H]imidacloprid has two binding sites with different affinities (Kd value of
      0.0035 +/- 0.0006 nM for the high-affinity site and 1.47 +/- 0.22 nM for the low
      affinity site). Although the cis-nitromethylene neonicotinoids showed low
      displacement ability (Ki values of 0.15 +/- 0.03 microM and 0.42 +/- 0.07 microM
      for IPPA152002 and IPPA152004, respectively) against [(3)H]imidacloprid binding,
      low concentrations (0.01 microM) of IPPA152002 completely inhibited
      [(3)H]imidacloprid binding at its high-affinity site. In Xenopus oocytes co
      injected with cRNA encoding Nlalpha1 and rat beta2 subunits, obvious inward
      currents were detected in response to applications of IPPA152002 and IPPA152004,
      although the agonist potency is reduced to that of imidacloprid. The previously
      identified Y151S mutation in Nlalpha1 showed significant effects on the agonist
      potency of IPPA152002 and IPPA152004, such as a 75.8% and 70.6% reduction in
      Imax, and a 2.4- and 2.1-fold increase in EC(50). This data clearly shows that
      the two newly described cis-nitromethylene neonicotinoids act on insect nAChRs
      and like imidacloprid, discriminated between high and low affinity binding sites
      in N. lugens native nAChRs. These compounds may be useful tools to further
      elucidate the pharmacology and nature of neonicotinoid binding sites.

PMID- 19849724
TI  - Expression of the Hsp83 gene in response to diapause and thermal stress in the
      moth Sesamia nonagrioides.
AB  - A full-length Hsp83, named SnoHsp83, cDNA from the corn stalk borer, Sesamia
      nonagrioides, was cloned and sequenced. Genomic analysis showed that the SnoHsp83
      gene is unique. The size of the SnoHsp83 cDNA was found to be approximately 2.6
      kb. The deduced polypeptide comprised 717 amino acid residues, with a molecular
      mass of 82.6 kDa. It contained all the highly conserved amino acid motifs that
      characterize the cytosolic members of the hsp90 family. We investigated the
      expression of SnoHsp83 gene in response to diapause and heat/cold stress.
      SnoHsp83 is constitutively expressed in non-diapausing larvae and is induced 15
      fold by heat. SnoHsp83 displays a similar pattern to SnoHsc70 under diapause
      conditions, when extra larval moults occur. Our results indicate that the
      SnoHsp83 gene could be involved in the developmental process that occurs between
      two moults.

PMID- 19849725
TI  - Haloarchaeal diversity in 23, 121 and 419 MYA salts.
AB  - DNA was extracted from surface-sterilized salt of different geological ages (23,
      121, 419 million years of age, MYA) to investigate haloarchaeal diversity. Only
      Haloarcula and Halorubrum DNA was found in 23 MYA salt. Older crystals contained
      unclassified groups and Halobacterium. The older crystals yielded a unique 55-bp
      insert within the 16S rRNA V2 region. The secondary structure of the V2 region
      completely differed from that in haloarchaea of modern environments. The DNA
      demonstrates that unknown haloarchaea and the Halobacterium were key components
      in ancient hypersaline environments. Halorubrum and Haloarcula appear to be a
      dominant group in relatively modern hypersaline habitats.

PMID- 19849726
TI  - A Hibiscus Abelmoschus seed extract as a protective active ingredient to favour
      FGF-2 activity in skin.
AB  - In the skin, heparin, heparan sulphate and heparan sulphate proteoglycans control
      the storage and release of growth factors and protect them from early
      degradation. We developed a cosmetic active ingredient containing Hibiscus
      Abelmoschus seed extract (trade name Linefactor) that can maintain the FGF-2
      content in the skin by mimicking the protective effect of heparan sulphate
      proteoglycans. By preventing the natural degradation of FGF-2, Hibiscus
      Abelmoschus seed extract maintains the bioavailability of this growth factor for
      its target cells, i.e. skin fibroblasts. Our in vitro evaluations showed that
      this ingredient exhibited heparan sulphate-like properties and dose-dependently
      protected FGF-2 from thermal degradation. We could also show that, in turn, the
      protected FGF-2 could stimulate the synthesis of sulphated GAGs, the natural
      protective molecules for FGF-2, thus providing a double protection. Finally, the
      in vitro results were confirmed in vivo thanks to a clinical study in which skin
      biomechanical properties and reduction in wrinkles were assessed.

PMID- 19849740
TI  - Vaccination and screening for infections in patients with inflammatory bowel
      disease: a survey of Australian gastroenterologists.
AB  - AIMS: To survey the practice among gastroenterologists in Australia relating to
      screening for latent infections and vaccination of patients with inflammatory
      bowel disease prior to treatment with tumour necrosis factor alpha (TNF-alpha)
      inhibitors. METHODS: A structured 15 question electronic survey was advertised to
      gastroenterologists in Australia through an email mailing list and through a
      hardcopy newsletter. RESULTS: Forty-four clinicians responded to the survey.
      Screening practice relating to latent tuberculosis infection and hepatitis B
      virus (HBV) was performed variably, with significant differences in screening
      methodology. Vaccination for HBV, influenza and pneumococcus was performed
      infrequently, and the timing of when vaccination should be offered varied
      considerably. CONCLUSIONS: Despite published guidelines advocating screening for
      latent infections and vaccination of patients treated with TNF-alpha inhibitors,
      compliance with recommendations was poor. Recommendations for screening and
      vaccination of these patients are provided based on these findings.

PMID- 19849741
TI  - Managing obstruction of the central airways.
AB  - Lung cancer is the most common cause of cancer death in Australia, Europe and the
      USA. Up to 20-30% of these cancers eventually affect the central airways and
      result in reduced quality of life, dyspnoea, haemoptysis, post-obstructive
      pneumonia and ultimately death. Non-malignant processes may also lead to central
      airway obstruction and can have similar symptoms. With the development of newer
      technologies, the last 20 years have seen the emergence of the field of
      interventional pulmonology to deal specifically with the diagnosis and management
      of thoracic malignancy, including obstruction of the central airways. This review
      discusses the pathology, pre-procedure work-up and management options for
      obstructing central airway lesions. Several treatment modalities exist for
      dealing with endobronchial pathology with local availability and expertise
      guiding choice of treatment. While the literature lacks large, multicentre,
      randomized studies defining the optimal management strategy for a given problem,
      there is growing evidence from numerous case studies of improved physiology, of
      quality of life and possibly of survival with modern interventional techniques.

PMID- 19849742
TI  - Intraperitoneal distribution imaging in ovarian cancer patients.
AB  - BACKGROUND/AIMS: Optimal delivery of intraperitoneal (i.p.) chemotherapy is
      dependent on adequate drug distribution. An accurate understanding of the
      limitations of i.p. distribution is critical if we are to improve cytotoxic
      delivery through this route. METHODS: Using repeated scintigraphic
      peritoneography we investigated peritoneal fluid distribution in patients
      receiving i.p. therapy. Both early (1-6 h) and late (24-48 h) images were
      performed. The peritoneal cavity was divided into six regions; pouch of Douglas,
      left and right paracolic gutters, left and right subphrenic spaces and the right
      subhepatic space. The distribution in each region was classified as absent (0),
      faint (1) or intense (2). A total distribution score was calculated from the
      summation of distribution values for each of the six regions. Distribution was
      then graded according to the total distribution score as follows: Grade 0 = 0-3;
      Grade 1 = 4-6; Grade 2 = 7-9; and Grade 3 = 10-12. RESULTS: Twenty-six
      participants were included in the study: all 26 patients had early imaging
      performed and 21 of these also had late imaging. Thirteen (50%) and 15 (71%)
      patients had grade 1 or 2 i.p. distribution on early and late imaging
      respectively. The most common abdominal regions to show maldistribution were the
      subphrenic spaces. CONCLUSIONS: This study highlights the deficiencies of
      distribution following i.p. drug delivery, with the majority of patients
      demonstrating multiple regions of faint or absent uptake on scintigraphic
      peritoneography imaging. Future large clinical studies investigating i.p.
      chemotherapy should include analyses of i.p. distribution to improve our
      understanding of optimal drug delivery through this route.

PMID- 19849743
TI  - Post-mortem drug concentrations.
AB  - Considerable changes occur in the concentrations of numerous drugs after death.
      Some concentrations increase, others fall and some do not change. Active agents,
      such as gamma hydroxybutyrate and alcohol, may be synthesized in the deceased
      body. Many published tables contain lists of therapeutic, toxic and lethal
      concentrations that are misleading. While the process of post-mortem
      redistribution of drugs has been called a 'toxicological nightmare', it is still
      possible to obtain a lot of information from the integration of ante-mortem
      history with the post-mortem drug concentration.

PMID- 19849744
TI  - Un-promoted issues in inflammatory bowel disease: opportunities to optimize care.
AB  - Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative
      colitis (UC), are chronic inflammatory disorders of the gut, which lead to
      significant morbidity and impaired quality of life (QoL) in sufferers, without
      generally affecting mortality. Despite CD and UC being chronic, life-long
      illnesses, most medical management is directed at acute flares of disease.
      Moreover, with more intensive medical therapy and the development of biological
      therapy, there is a risk that management will become even more narrowly focused
      on acute care, and be directed only at those with more severe disease, rather
      than encompassing all sufferers and addressing important non-acute issues. This
      imbalance of concentration of medical attention on 'high-end' care is in part
      driven by the need to perform and publish randomized clinical trials of newer
      therapies to obtain registration and licensing for these agents, which thus
      occupy a large proportion of the recent IBD treatment literature. This leads to
      less attention on relatively 'low-technology' issues including: (i) the
      psychosocial burden of chronic disease, QoL and specific psychological
      comorbidities; (ii) comorbidity with functional gastrointestinal disorders
      (FGIDs); (iii) maintenance therapy, monitoring and compliance; (iv) smoking (with
      regard to CD); (v) sexuality, fertility, family planning and pregnancy; and (vi)
      iron deficiency and anaemia. We propose these to be the 'Un-promoted Issues' in
      IBD and review the importance and treatment of each of these in the current
      management of IBD.

PMID- 19849745
TI  - Cardiovascular mortality and morbidity in chronic obstructive pulmonary disease:
      the impact of bronchodilator treatment.
AB  - Chronic obstructive pulmonary disease (COPD) is a substantial health burden.
      Cardiovascular disease (CVD), the leading cause of death, frequently coexists
      with COPD, an effect attributed to high individual disease prevalences and shared
      risk factors. It has long been recognized that COPD, whether stable or during
      acute exacerbations, is associated with an excess of cardiac arrhythmias.
      Bronchodilator medications have been implicated in the excess CVD seen in COPD,
      either as an intrinsic medication effect or related to side-effects. Despite the
      theory behind increased pro-arrhythmic effects in COPD, the reported results of
      trials investigating this for inhaled formulations at therapeutic doses are few.
      Methodological flaws, retrospective analysis and inadequate adjustment for
      concomitant medications, including short-acting 'relief' bronchodilators and non
      respiratory medications with known arrhythmia propensity, mar many of these
      studies. For most bronchodilators at therapeutic levels in stable COPD, we can be
      reassured of their safety from current studies. The exception to this is
      ipratropium bromide, where the current data indicate an association with
      increased cardiovascular adverse effects. Moreover, there is no proven benefit
      from combining short-acting beta-agonists with short-acting anticholinergics at
      high doses in the acute setting, and although this practice is widespread, it is
      associated with increased cardiovascular risk.

PMID- 19849746
TI  - Long-term percutaneous endoscopic gastrostomy feeding in young adults with
      multiple disabilities.
AB  - AIM: To study the outcomes from initiation of percutaneous endoscopic gastrostomy
      (PEG) feeding in young people with profound multiple disabilities. METHODS:
      Observations were made on 40 adults with lifelong intellectual disability (mental
      retardation) and quadriplegia, in whom PEG feeding was initiated during 1990
      2008. There were 20 men and 20 women aged 15-40 years at the time of the audit,
      living in settings with 24 h registered nurse staffing. RESULTS: Undernutrition
      and recurrent aspiration with frequent infections were cited as reasons for PEG
      feeding. The positive outcomes were that some were said to be more alert for a
      time following the procedure; and these young adults lived with PEG feeding for
      an average of 8.5 years, some up to 18 years. In that time, however, they all
      experienced complications of the PEG insertion, and of the PEG feeding process.
      There were no measurable improvements in cognition. There were no reductions in
      prescription of medications. They all required frequent daily interventions by
      nurses to maintain medical stability. Ten people died during this review period,
      from continued deterioration in neurological status, with pneumonia cited as the
      terminal event. CONCLUSIONS: Unlike other people with neurological deterioration,
      young adults with lifelong multiple disabilities may live for many years with PEG
      feeding. There is little gain in quality of life.

PMID- 19849747
TI  - Clinical and biochemical characteristics of patients with thyroid-stimulating
      hormone-secreting pituitary adenomas from one New Zealand centre.
AB  - BACKGROUND: Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas
      (TSHoma) are a rare cause of thyrotoxicosis and need to be distinguished from the
      syndrome of resistance to thyroid hormone. Patients with TSHoma may also be
      misdiagnosed as having primary hyperthyroidism and receive inappropriate
      treatment directed towards the thyroid gland. METHODS: We performed a
      retrospective review of patients with TSHoma who presented to one New Zealand
      endocrine service between 1989 and 2003. RESULTS: Six patients with TSHoma were
      managed during this time period. All patients had elevated free thyroid hormone
      levels with elevated, or inappropriately normal, TSH levels. The median age at
      presentation was 43 years and the median time from symptom onset to correct
      diagnosis was 3 years (range 0.25-12 years). Five patients had a macroadenoma at
      the time of diagnosis. Three had been treated elsewhere for primary
      hyperthyroidism prior to referral. Three patients received octreotide as primary
      treatment with two of these patients later undergoing transsphenoidal resection
      of the pituitary adenoma. CONCLUSION: With increased awareness and earlier
      diagnosis of TSH-secreting pituitary adenomas, management can be appropriately
      directed towards the pituitary.

PMID- 19849748
TI  - Predictors of long-term mortality in the elderly: the Dubbo Study.
AB  - BACKGROUND: This study examines the predictors of long-term all-causes mortality
      (ACM) in Australian senior citizens. METHODS: We have analysed ACM in a cohort of
      2805 citizens, 1233 men and 1572 women aged >=60 years, first examined in 1988
      and followed for 20 years. Hazard ratios and 95% confidence intervals for ACM
      were obtained from Cox models employing conventional predictors. RESULTS: Over 20
      years 66% of men (815/1233) and 53% of women (833/1572) died. Constant
      proportional hazard over the 20 years was demonstrated for all predictors,
      indicating similar relative hazard of ACM during long-term or short-term follow
      up. There was significant prediction of ACM by current smoking (hazard ratio
      1.96, 95% confidence interval 1.57-2.43 in men; 1.67, 1.32-2.10 in women), high
      blood pressure (1.37, 1.03-1.81; 1.41, 1.07-1.86), diabetes (1.46, 1.17-1.82;
      1.83, 1.43-2.34), impaired peak expiratory flow (1.39, 1.15-1.69; 1.80, 1.47
      2.21), coronary heart disease at study entry in men (1.33, 1.13-1.57), physical
      disability (1.38, 1.13-1.68; 1.45, 1.17-1.79) and alcohol intake (0.82, 0.69
      0.97; 0.77, 0.66-0.89 respectively). ACM was not significantly predicted by
      standard lipid parameters. Over the 20-year period smoking was associated with
      reduced survival of 41 months in men and 25 months in women, hypertension with
      reduced survival of 20 and 17 months, and diabetes with reduced survival of 24
      and 30 months respectively. CONCLUSIONS: The findings confirm the contribution of
      cigarette smoking, hypertension and diabetes to ACM in senior citizens,
      conditions that are potentially amenable to intervention.

PMID- 19849749
TI  - Continuity of care: when do patients visit community healthcare providers after
      leaving hospital?
AB  - BACKGROUND/AIMS:   Enhanced communication and transfer of information between
      healthcare providers and healthcare settings can reduce medication and healthcare
      errors post-hospital discharge. The timeframes within which patients access
      community healthcare providers post-hospital discharge are not well studied. This
      study aimed to determine length of time from hospital discharge until a general
      practice, pharmacy or specialist visit, or care planning service. METHODS:   We
      conducted a retrospective analysis of Department of Veterans' Affairs health
      claims data. All 109 860 veterans hospitalized in 2006 were included. Main
      outcome measures were time from first hospital discharge to first claim for a
      general practice, pharmacy, specialist visit and/or care planning service.
      RESULTS:   Within 30 days of hospital discharge 71% of subjects visited a general
      practitioner (GP), 86% had medicines dispensed from a community pharmacy and 44%
      saw a specialist. Median time to first pharmacy visit was 6 days (interquartile
      range 2-14) and 12 days for a GP visit (interquartile range 4-31). Less than 2%
      of the cohort received a discharge plan, case conference or medication review in
      the month after discharge. CONCLUSIONS:   With 25% of patients having a claim for
      a GP service within 4 days of discharge, discharge summaries need to reach
      community-based health professionals within this time. Most patients visited
      their community pharmacy within 2 weeks of hospital discharge and before they saw
      their GP. Pharmacists are not routinely advised of hospitalization or provided
      with discharge summaries. More active engagement of this professional group in
      the continuum of care might improve care after hospital discharge.

PMID- 19849750
TI  - Prevalence and predictors of premature discontinuation of dual antiplatelet
      therapy after drug-eluting stent implantation: importance of social factors in
      Asian patients.
AB  - AIM: Premature discontinuation of antiplatelet therapy is an independent
      predictor of late stent thrombosis. We sought to determine the prevalence and
      predictors of premature discontinuation of antiplatelet therapy after drug
      eluting stent implantation among patients in Asia. METHODS: A total of 207
      consecutive patients who underwent drug-eluting stent implantation at our
      institution was followed up after 1 year. Premature discontinuation of
      antiplatelet therapy was defined as omission of aspirin and/or clopidogrel for 1
      week or more. RESULTS: Four (1.9%) patients died and the remaining 203 patients
      formed the study population. Prevalence of premature discontinuation of
      antiplatelet therapy was 12.8% (n= 26, aspirin, n= 12; clopidogrel, n= 9; both,
      n= 5). The median duration between stent implantation and discontinuation of
      antiplatelet therapy was 2.8 months. Reasons for discontinuation included cost
      (n= 1), gastric discomfort (n= 1), allergy (n= 3), bleeding (n= 3), advice from
      doctors (n= 7) and no reason (n= 11). Logistic regression showed that living
      alone was the only independent predictor of premature discontinuation of dual
      antiplatelet therapy (50.0% vs 11.3%, P= 0.001). CONCLUSION: Among Asian patients
      who have undergone drug-eluting stent implantation, 12.8% discontinued dual
      antiplatelet therapy within 12 months. Living alone is associated with a fivefold
      increase in risk of premature drug discontinuation.

PMID- 19849751
TI  - The utility of transoesophageal echocardiography to determine management in
      suspected embolic stroke.
AB  - BACKGROUND: Assessment for source of stroke is a common indication for
      transoesophageal echocardiography (TOE). Although an abnormality is frequently
      found, it remains uncertain how frequently the findings alter patient management.
      Also, the role of transthoracic echocardiography (TTE) prior to or instead of TOE
      is not well defined. We sought to determine the use of TTE prior to TOE, the
      outcome of the TOE and its impact on management. METHODS: We retrospectively
      reviewed the records and echocardiography results of 100 consecutive patients who
      underwent TOE for any reason at a tertiary hospital. In 35 subjects (35%), the
      indication was evaluation for source of stroke. Among these, we determined
      clinical risk factors for stroke, if a TTE was performed prior to their TOE, the
      results of the TOE and its effect on management. RESULTS: The mean age of the
      stroke patients was 64.6 years (17-90) and 49% were women. Eighty per cent had at
      least one risk factor for stroke and 17% had atrial fibrillation. A TTE,
      performed in 40% prior to the TOE, found an abnormality in 14% (2/14). The TOE
      showed an abnormality in 71% of patients; 54% had aortic atheroma; 17% PFO; 14%
      spontaneous echo contrast; 6% left atrial appendage thrombus, 3% left ventricular
      thrombus and 3% vegetation. In only one patient (3%) the management was altered
      based on the abnormal TOE findings. CONCLUSION: An abnormality on TOE, although
      common (71%) and more sensitive than TTE, altered management in only 3% of
      subjects referred for stroke assessment. Its role requires further consideration.

PMID- 19849752
TI  - The potential value of faecal lactoferrin as a screening test in hospitalized
      patients with diarrhoea.
AB  - BACKGROUND: Nosocomial diarrhoea is common and its investigation carries a
      significant healthcare cost. This study aimed to determine the utility of faecal
      lactoferrin (FL), a readily measurable marker of intestinal inflammation, in
      hospitalized patients with diarrhoea. METHODS: FL was quantified in consecutive
      faecal samples submitted to a hospital pathology laboratory. Patient data were
      extracted from hospital records. Receiver-operator curve (ROC) analysis was
      performed in a subset of patients where a decision about low or high likelihood
      of inflammation could be confidently made. Multivariate analyses were performed
      to identify associations with an elevated FL. Cost analyses were also performed.
      RESULTS: A total of 511 faecal samples from 433 patients (48% male, median age 67
      years) was studied. Median FL concentration was 3.4 ug/mL (range 0-288). ROC
      analysis indicated an optimal cut-off value of 1.25 ug/mL (sensitivity 92%,
      specificity 97%, negative predictive value 97%) compared with the manufacturer's
      cut-off of 7.25 ug/mL (60%, 66% and 85% respectively). Multivariate analysis at
      the lower cut-off minimized potentially confounding variables. Proton pump
      inhibitor use independently increased (OR 2.3, 95% CI 1.5-3.8) and current
      smoking reduced (0.61, 0.38-0.99) the likelihood of an elevated FL. Only one out
      of 32 bacteriological positive samples would have been missed if FL was
      instituted as a screening test prior to microbiological assessment, which could
      have reduced laboratory-related costs by up to 56%. CONCLUSION: In hospitalized
      patients, a normal FL effectively excludes inflammatory diarrhoea and is proposed
      as a screening test prior to microbiological assessment of faeces. Prospective
      evaluation of this approach is warranted.

PMID- 19849753
TI  - Chronic neck pain following car crashes: a population-based study from Auckland,
      New Zealand.
AB  - BACKGROUND:   In a setting with a 'no fault' universal government-funded accident
      compensation system, we undertook a study to (i) estimate the prevalence and
      predictors of chronic neck pain in car occupants surviving serious injury
      producing crashes and (ii) compare the longer-term health-related quality of life
      of crash survivors with and without neck discomfort. METHODS:   A prospective
      cohort study recruited hospitalized survivors aged >=16 years and non
      hospitalized drivers of cars involved in serious crashes in Auckland over a 10
      month period. Participants completed a structured questionnaire at recruitment
      and 5 and 18 months later. RESULTS:   Of the 268 participants, 50 (18.7%)
      reported neck pain or stiffness at 5 and 18 months following the crash. Of these,
      70% noted the discomfort led to limitations in work and recreation. Depressive
      and post-traumatic stress symptoms at 5 months were associated with an increased
      risk of moderate to severe neck discomfort at 18 months. Participants with and
      without neck discomfort had significantly reduced health-related quality of life
      based on Short Form-36 scores. CONCLUSION:   Significant neck discomfort limiting
      usual function is relatively common up to 18 months following crashes. The
      reductions in health status among crash survivors with and without neck pain
      reveal the complexities in attributing longer-term adverse outcomes to a
      particular condition in the absence of an appropriate comparison group. The
      findings indicate the need to manage judiciously comorbid conditions while
      prioritizing efforts to support crash survivors' return to their usual social
      roles and activities.

PMID- 19849754
TI  - Physicians need to understand the importance of information technology in the
      21st century.

PMID- 19849755
TI  - Why can't I prescribe that antibiotic? The role of antimicrobial stewardship
      programmes in modern medicine.

PMID- 19849756
TI  - Are specialist physicians missing out on the e-Health boat?
AB  - BACKGROUND: Nationally health systems are making increasing investments in the
      use of clinical information systems. Little is known about current computer use
      by specialist physicians, particularly outside the hospital setting. AIMS: To
      identify the extent and reasons physician Fellows of the Royal Australasian
      College of Physicians (RACP) use computers in their work. METHODS: A self
      administered survey was emailed from the RACP to all practising physicians in
      2007 that were living in Australia and New Zealand who had consented to email
      contact with the College. RESULTS: The survey was sent to a total of 7445
      eligible physicians, 2328 physicians responded (31.3% response rate), but only
      1266 responses (21.0%) were able to be analysed. Most 97.5% had access to
      computers at work and 96.5% used home computers for work purposes. Physicians in
      public hospitals (72.6%) were more likely to use computers for work (65.6%) than
      those in private hospitals (12.6%) or consulting rooms (27.3%). Overall
      physicians working in public hospitals used a wider range of applications with
      70.5% using their computers for searching the internet, 53.7% for receiving
      results and 52.7% used their computers to engage in specific educational
      activities. Physicians working from their consulting rooms (33.6%) were more
      likely to use electronic prescribing (11%) compared with physicians working in
      public hospitals (5.7%). CONCLUSIONS: Fellows have not incorporated computers
      into their consulting rooms over which they have control. This is in contrast to
      general practitioners who have embraced computers after the provision of various
      incentives. The rate of use of computers by physicians for electronic prescribing
      in consulting rooms (11%) is very low in comparison with general practitioners
      (98%). One reason may be that physicians work in multiple locations whereas
      general practitioners are more likely to work from one location.

PMID- 19849757
TI  - Evidence-based management of heart failure in clinical practice: a review of
      device-based therapy use.
AB  - BACKGROUND: Heart failure is a growing health issue and is associated with
      significant mortality risk. Device therapy is efficacious in preventing sudden
      death in patients with heart failure; however, this evidence comes from rigorous
      clinical trials. It is unclear how device therapy is utilized in 'real-world'
      practice. The primary objective was to characterize patterns of device use in
      patients with heart failure at risk of sudden death and to identify barriers to
      guideline-driven prescription of implantable cardioverter-defibrillators.
      METHODS: We report a cross-sectional study of patients attending general
      cardiology clinic over a 3-month period. RESULTS: Of 1003 consecutive patients
      attending the cardiology clinic, 176 had heart failure. Of these, 66 were
      potentially eligible for device therapy, but only 16 of these had actually
      undergone device implantation. Potentially eligible non-recipients were older (P
      < 0.001), more likely to have ischaemic cardiomyopathy (P= 0.002), less likely to
      be prescribed spironolactone (P= 0.005) or warfarin (P= 0.02), and less likely to
      have a widened QRS > 120 ms (P= 0.005). There was a high prevalence of underuse
      of evidence-based pharmacotherapies among patients with heart failure.
      CONCLUSION: There is substantial underuse of device therapy in patients with
      heart failure. Strikingly, whereas patients with symptoms of heart failure were
      more likely to receive a device, those being managed for ischaemic heart disease
      were not. There is also a high prevalence of failure to prescribe evidence-based
      pharmacotherapy in a tertiary hospital general cardiology clinic. This may be
      explained in part by the lack of a patient database to record treatment
      contraindications and to alert clinicians to possible gaps in patient therapy.

PMID- 19849758
TI  - Testing the outcome score of spontaneous intracerebral haemorrhage in
      haemodialysis patients.
AB  - The aim of this study is to determine the predictive value of the spontaneous
      intracerebral haemorrhage (ICH) outcome score (which we described previously) in
      haemodialysis (HD) patients who develop spontaneous ICH. The validation cohort
      consisted of all HD patients with spontaneous ICH presenting to Chang Gung
      Memorial Hospital in Taiwan during 2005-2007. The data were collected from one
      hospital and prospectively analysed, and the predictive model was tested using an
      external validation dataset. The prognostic factors were confirmed by chi-squared
      testing. We calculated the 30-day mortality in different groups of the validation
      cohort divided according to outcome score and tested the predictive value of the
      outcome score. The overall mortality rate was 52.6% in 38 HD patients. The
      originally identified prognostic factors were Glasgow Coma Scale score, age
      >or=70 years, systolic blood pressure <130 or >or=200 mmHg, ICH volume >or=30 mL,
      presence of intraventricular haemorrhage and serum glucose >or=8.8 mmol/L. All
      but one (serum glucose >or=8.8 mmol/L (P= 0.07)) were subsequently found to be
      associated with 30-day mortality. In patients scoring 6 and 7, mortality was
      100%, but in patients scoring 0, it was only 11.1%. The 30-day mortality in the
      validation cohort increased steadily with score and had good predictive value
      (correlation coefficient = 0.986, P < 0.001). Similar results in two different
      cohorts indicate that the ICH outcome score is a reliable outcome measure.

PMID- 19849759
TI  - The development and implementation of the pathway for improving the care of the
      dying in general medical wards.
AB  - The majority of deaths in Australia occur in general hospital wards and most are
      neither sudden nor unexpected. The Pathway for Improving the Care of the Dying
      (PICD) is an adaptation of the Liverpool Care Pathway to the Australian
      healthcare setting (or 'to Australian conditions') and is designed to help ensure
      a 'good death' for patients dying outside the palliative care system. PICD
      consists of a series of prompts, guidelines, revised medical and nursing care
      plans and a number of medication algorithms.

PMID- 19849760
TI  - The occurrence of asthma in hospitalized patients with type 2 diabetes mellitus.
AB  - Diabetes mellitus (DM) has been found to be associated with cardiovascular
      disease. The goal of this study is to evaluate the prevalence of asthma in
      patients with type II DM after adjusting for other comorbid conditions. We used
      patient treatment files of inpatients' admissions containing discharge diagnosis
      (Classification of Mental and Behavioural Disorders (ICD)-9 codes) from Veterans
      Health Administration Hospitals. The patients were divided into two groups: ICD-9
      code for DM and a control group with hypertension but no DM. ICD-9 codes for
      asthma were used to study the prevalence of asthma in DM patients versus the
      control. We performed uni- and multi-variable analysis adjusting for comorbid
      conditions. Asthma was present in 13 242 (4.5%) of DM patients versus 16 038
      (2.9%) in the control group. Using multi-variable analysis, DM remained
      independently associated with asthma (odds ratio: 2.99; confidence interval: 2.92
      3.06; P < 0.0001). The prevalence of asthma is significantly higher in
      hospitalized patients with type II DM independent of other comorbid conditions.
      The pathogenesis of this association is not known warranting further
      investigation.

PMID- 19849761
TI  - Bad dental hygiene: don't let it go to your head.

PMID- 19849762
TI  - Haematological manifestation of coeliac disease in a young patient with
      myocardial infarction.

PMID- 19849763
TI  - Clinical and molecular complete remission of primary duodenal follicular lymphoma
      following treatment with rituximab and cyclophosphamide, vincristine and
      prednisone chemotherapy.

PMID- 19849764
TI  - Peripheral neuropathy on imatinib treatment for chronic myeloid leukaemia:
      suspected adverse drug interaction with amlodipine.

PMID- 19849765
TI  - Non-alcoholic fatty liver disease and microalbuminuria in non-diabetic patients:
      role of insulin resistance.

PMID- 19849766
TI  - Faecal immunological test blues: is there a psychiatric morbidity associated with
      the National Bowel Cancer Screening Program?

PMID- 19849767
TI  - Rapid relief of acute sore throat with AMC/DCBA throat lozenges: randomised
      controlled trial.
AB  - AIM: As antibiotics are generally not recommended for the treatment of acute sore
      throat, the availability of clinically efficacious, over-the-counter (OTC)
      treatment alternatives is becoming increasingly important. This study was
      designed to determine the analgesic properties of amylmetacresol and 2,4
      dichlorobenzyl alcohol (AMC/DCBA) throat lozenges (Strepsils) in the relief of
      acute sore throat caused by upper respiratory tract infections. METHODS: Patients
      (n = 310) were randomly assigned to receive AMC/DCBA throat lozenges (n = 155) or
      non-medicated placebo lozenges (n = 155). After baseline assessments, patients
      completed three rating assessments at 10 timepoints from 5 to 20 min after first
      dose. Subsequent lozenges were taken as required, and assessments were made at
      the end of Day 1, 24 h after first dose, and at the end of Days 2 and 3.
      Analgesic properties were assessed by comparing severity of throat soreness and
      sore throat relief ratings. Difficulty in swallowing and functional impairment
      scores were also assessed. RESULTS: Amylmetacresol/DCBA throat lozenges reduced
      throat soreness at 5 min after first dose, which persisted for 2 h and was
      significantly different vs. non-medicated lozenges at all assessment timepoints
      for the duration of the 3-day study. Similar significant effects were observed
      with sore throat relief, easing of difficulty with swallowing and functional
      impairment scores. There were no differences in adverse events reported between
      treatment groups. CONCLUSION: Amylmetacresol/DCBA throat lozenges provide rapid
      analgesic effects that last for 2 h, providing ongoing relief long after the
      lozenge has dissolved. The superior analgesic effects and improvements in
      functional impairment scores observed with AMC/DCBA throat lozenges translate
      into pain relief benefits that are clinically meaningful and are thus a suitable
      OTC treatment option for patients in the self-management of acute sore throat.

PMID- 19849768
TI  - Is it worthwhile to offer repeat hydrodilatation for frozen shoulder after 6
      weeks?
AB  - AIMS: Frozen shoulder is a common problem for which hydrodilatation is an
      established treatment option although the optimal regime is not yet established.
      We asked 'is it worthwhile to offer a repeat hydrodilatation procedure after 6
      weeks?' METHODS: A total of 36 patients diagnosed with frozen shoulder and
      undergoing hydrodilatation were evaluated. All patients had an initial
      hydrodilatation and were offered a repeat procedure after 6 weeks. Of the total
      patients, 22 chose to undergo a repeat procedure. The Shoulder Disability
      Questionnaire UK Score and Oxford Shoulder Score were used to evaluate pre- and
      postprocedure outcome. The mean follow up was 15.4 months. RESULTS: The Oxford
      Shoulder Score improved by a significant level after both single (30.5-17.1) and
      repeat hydrodilatation (36.0-21.4). No significant change was observed after
      either procedure when using the Shoulder Disability Questionnaire UK Score as an
      outcome measure. CONCLUSIONS: The data are suggestive that routine
      hydrodilatation after 6 weeks is not appropriate and should be instead offered to
      those patients who can tolerate it and who have not fully benefitted after a
      single procedure.

PMID- 19849769
TI  - Antimicrobial-resistant faecal Escherichia coli in wild mammals in central
      Europe: multiresistant Escherichia coli producing extended-spectrum beta
      lactamases in wild boars.
AB  - AIMS: To determine the presence of antibiotic-resistant faecal Escherichia coli
      in populations of wild mammals in the Czech Republic and Slovakia. METHODS AND
      RESULTS: Rectal swabs or faeces collected during 2006-2008 from wild mammals were
      spread on MacConkey agar and MacConkey agar containing 2 mg l(-1) of cefotaxime.
      From plates with positive growth, one isolate was recovered and identified as E.
      coli. Susceptibility to 12 antibiotics was tested using the disk diffusion
      method. Resistance genes, class 1 and 2 integrons and gene cassettes were
      detected in resistant isolates by polymerase chain reaction (PCR). Extended
      spectrum beta-lactamases (ESBL) were further characterized by DNA sequencing,
      macrorestriction profiling and determination of plasmid sizes. Plasmid DNA was
      subjected to EcoRV digestion, transferability by conjugation and incompatibility
      grouping by multiplex PCR. The prevalence of resistant isolates was 2% in small
      terrestrial mammals (rodents and insectivores, n(E. coli) = 242), 12% in wild
      ruminants and foxes (n(E. coli) = 42), while no resistant isolates were detected
      in brown bears (n(E. coli) = 16). In wild boars (Sus scrofa) (n(E. coli) = 290),
      the prevalence of resistant isolates was 6%. Class 1 and 2 integrons with various
      gene cassettes were recorded in resistant isolates. From wild boars, five (2%,
      n(rectal smears) = 293) multiresistant isolates producing ESBL were recovered:
      one isolate with bla(CTX-M-1) + bla(TEM-1), three with bla(CTX-M-1) and one with
      bla(TEM-52b). The bla(CTX-M-1) genes were carried on approx. 90 kb IncI1
      conjugative plasmids. CONCLUSIONS: Antibiotic-resistant E. coli occurred in
      populations of wild mammals in various prevalences. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Wild mammals are reservoirs of antibiotic-resistant E. coli including
      ESBL-producing strains which were found in wild boars.

PMID- 19849770
TI  - The aerobiology of the environment around mechanically ventilated broiler sheds.
AB  - AIM: To investigate the aerobiology of the environment around mechanically
      ventilated broiler sheds with the aim of understanding dispersion in the
      surrounding environment. METHODS AND RESULTS: Aerosol samples were collected
      weekly on four different commercial broiler farms through the cycle of 55 days
      from 2005 to 2007. Samples were collected inside the shed and at varying
      distances from the sheds. Litter and dust from within the shed were also
      examined. Members of the genera Staphylococcus (and to a lesser extent
      Corynebacterium) dominated (10(6) CFU m(-3)) in the outside air at 20 m from the
      fan and were shown to decrease with distance. At distances of around 400 m, the
      levels of staphylococci/coryneforms returned to levels typical of those present
      before the placement of chickens. Escherichia coli levels were low (maximum 100
      CFU m(-3)) at 20 m. Fungi were present at uniform levels across the broiler
      cycle. CONCLUSIONS: Staphylococci are the dominant organisms present in the air
      around mechanically ventilated broiler sheds and have the potential to act as an
      airborne 'marker organism'. SIGNIFICANT IMPACT OF THE STUDY: The outcomes of this
      study suggest that the impact of aerosols emitted from broiler sheds could be
      monitored and managed by examining the levels of staphylococci/coryneforms.

PMID- 19849771
TI  - Characterization and heterologous expression of a novel lysophospholipase gene
      from Antrodia cinnamomea.
AB  - AIMS: A novel lysophospholipase (LysoPL) from the basidiomycetous fungi Antrodia
      cinnamomea named ACLysoPL was cloned, heteroexpressed in Escherichia coli and
      characterized. METHODS AND RESULTS: The gene encoding ACLysoPL was obtained from
      expressed sequence tags from A. cinnamomea. The full length of this gene has a
      945 -bp open reading frame encoding 314 amino acids with a molecular weight of
      35.5 kDa. ACLysoPL contains a lipase consensus sequence (GXSXG) motif and a Ser
      His-Asp catalytic triad. A putative peroxisomal targeting signal type 1 was found
      in the C-terminal. Heterologous expression of ACLysoPL in E. coli showed that the
      enzyme preferentially hydrolyses long-chain acyl esterases at pH 7 and 30 degrees
      C. ACLysoPL is a psychrophilic enzyme about 40% of whose maximum activity
      remained at 4 degrees C. The LysoPL activities with lysophospholipids as
      substrate were analysed by gas chromatography/mass spectrometry. CONCLUSION: We
      have identified and characterized a gene named ACLysoPL encoding a protein
      performing LysoPL and esterase activities. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first LysoPL of A. cinnamomea identified and characterized at the
      molecular level.

PMID- 19849772
TI  - A real-time PCR assay for detection and quantification of Lactococcus garvieae.
AB  - AIMS: To develop a rapid, sensitive, specific tool for the detection and
      quantification of Lactococcus garvieae in food and environmental samples. METHODS
      AND RESULTS: A real-time quantitative PCR (qPCR) assay with primers for CAU12F
      and CAU12R based on the 16S rRNA gene of L. garvieae was successfully
      established. The limit of detection for L. garvieae genomic DNA was 1 ng DNA in
      conventional PCR and 32 fg with a mean C(T) value of 36.75 in qPCR.
      Quantification of L. garvieae vegetative cells was linear (R(2) = 0.99) over a 7
      log-unit dynamic range down to ten L. garvieae cells. CONCLUSIONS: This method is
      highly specific, sensitive and reproducible for the detection of L. garvieae
      compared to gel-based conventional PCR assays, thus providing precise
      quantification of L. garvieae in food and natural environments. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work provides efficient diagnostic and monitoring tools
      for the rapid identification of L. garvieae, an emerging pathogen in aquaculture
      and an occasional human pathogen from other members of the genus Lactobacillus.

PMID- 19849773
TI  - Natural whey starter for Parmigiano Reggiano: culture-independent approach.
AB  - AIMS: The aim of this work was to obtain a deeper insight into the knowledge of
      microbial composition of Parmigiano Reggiano natural whey starters through
      different culture-independent methods. METHODS AND RESULTS: Eighteen different
      Parmigiano Reggiano natural whey starters sampled from three different provinces
      of this cheese production area and the nonacidified wheys from which they arose
      have been studied by length heterogeneity polymerase chain reaction (LH-PCR) and
      fluorescent in situ hybridization (FISH). A high microbial composition
      variability between different samples has been observed. CONCLUSIONS: Revealing
      different images of the same community, LH-PCR and FISH have given a more
      accurate view of the not well-known Parmigiano Reggiano whey starter ecosystem.
      SIGNIFICANCE AND IMPACT OF THE STUDY: New lights have been shed on Parmigiano
      Reggiano natural whey starters microbial composition, highlighting how culture
      independent approach could be used and improved to study this and other food
      ecosystems.

PMID- 19849774
TI  - Predictive value of on-treatment response during full-dose antiviral therapy of
      patients with hepatitis C virus cirrhosis and portal hypertension.
AB  - OBJECTIVE: Therapy with full-dose pegylated interferon (PEG-IFN) and weight-based
      ribavirin has been evaluated in limited series of patients with hepatitis C virus
      (HCV) and advanced disease. In this study, we evaluated the efficacy and
      tolerability of full-dose antiviral therapy in patients with compensated, fully
      developed cirrhosis, and assessed the predictive value of on-treatment
      virological response. DESIGN AND SUBJECTS: We studied 85 HCV-positive cirrhotic
      patients (82 Child-Pugh class A; 41 treatment-naive) who were treated with PEG
      IFN alpha-2(a) (1.5 microg kg(-1)week(-1)) or alpha-2(b) (180 microg week(-1))
      and weight-based ribavirin for 24 (genotype 2-3) or 48 (genotype 1-4) weeks.
      Forty-three patients were genotype 1 (51%), and HCV-RNA was >600,000 IU mL(-1) in
      53 patients (62%). Prevalence of portal hypertension and diabetes was 81% and 18%
      respectively. RESULTS: Sustained virological response (SVR) was obtained in 22
      patients (26%). Positive serum HCV-RNA at week 4 and week 12 of therapy predicted
      nonresponse (NR) in 85% (52/61) and 100% (38/38) of patients, respectively.
      Treatment was discontinued due to adverse events in 14 patients (16%). Genotype 1
      4 (P = 0.02) and HCV-RNA >600,000 IU mL(-1) (P = 0.02) were the baseline
      parameters significantly associated with lack of SVR, whilst positive serum HCV
      RNA at week 12 was the only parameter independently associated with NR (100%
      negative predictive value). CONCLUSION: Full-dose antiviral therapy with PEG-IFN
      and ribavirin can be safely carried out even in patients with compensated, fully
      established cirrhosis and portal hypertension. Selecting patients on the basis of
      HCV genotype and viral load, and application of on-treatment stopping rule may
      help rationalize treatment in patients who are unlikely to obtain SVR.

PMID- 19849775
TI  - Retention of zirconia copings on zirconia implant abutments cemented with
      provisional luting agents.
AB  - The purpose of this study is to measure and compare the retentive force of
      zirconia-based all-ceramic crowns cemented on zirconia abutments using five
      provisional luting agents. In addition, the effect of sandblasting and
      thermocycling on the retentive force was evaluated. Two hundred zirconia
      abutments and copings were fabricated (Procera system; Nobel Biocare) and divided
      into five groups. Hy bond temporary cement hard (Hard), Hy bond temporary cement
      soft (Soft), experimental temporary cement (New), Tempbond NE (Temp) and
      Freegenool temporary pack (Pack) were used according to the manufacturers'
      instructions. Each group was divided into two groups, one with and one without
      sandblasting. Furthermore, thermocycling up to 2000 cycles was conducted on half
      of each group. After 24 h and thermocycling, the retentive force was measured
      using a universal testing machine. The data were subjected to analysis of
      variance, and comparisons of the means were performed with a Games-Howell test at
      a level of 95%. As a result, Hard showed the highest retentive force,
      sandblasting was effective for improving the durability, and no effect of
      sandblasting was detected in the others. New showed stability of the retentive
      force even after thermocycling. The retentive force of Temp and Pack decreased
      significantly after thermocycling even with sandblasting. The retentive forces
      were different from the provisional cement and sandblasting, and Temp and Pack
      may not be appropriate for the retention of single-tooth zirconia abutments and
      coping restorations.

PMID- 19849776
TI  - Vitamin D and the risk of acute allograft rejection following human liver
      transplantation.
AB  - BACKGROUND: Vitamin D may act as an immune modulator in experimental and human
      organ transplantation, but these data are yet to be confirmed in human liver
      transplantation (LT). AIM: This study aimed to assess the relationship between
      acute liver allograft cellular rejection (ACR) and pretransplant serum vitamin D
      concentration or post-transplant vitamin D supplementation. METHOD: We studied
      133 LT recipients who underwent two per protocol allograft biopsies in the early
      post-operative period, plus on-demand biopsies as clinically indicated. ACR
      estimate was given according to the Banff scheme in biopsies obtained along two
      follow-up periods: (a) from the transplant operation to the end of the second
      month (0-2 months); (b) and from the third month to the end of the eighth month
      (3-8 months) post-LT. RESULTS: The median pretransplant serum 25-hydroxyvitamin D
      concentration was 12.5 ng/ml; 40 patients had concentrations < or =12.5 ng/ml, of
      whom six had < or =5.0 ng/ml. Seventy-nine recipients received oral vitamin D(3)
      supplementation to treat post-transplant osteoporosis. In the 0-2 months period,
      moderate-to-severe rejection episodes were independently associated with
      cytomegalovirus reactivation (P<0.005) and progressively lower pretransplant
      serum 25-hydroxyvitamin D concentrations (P<0.02). Early vitamin D(3)
      supplementation was independently associated with a lack of ACR (P<0.05).
      CONCLUSIONS: These results suggest that vitamin D may favour immune tolerance
      towards the liver allograft.

PMID- 19849777
TI  - Diabetes mellitus as an independent prognostic predictor and its association with
      renal dysfunction in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Patients with hepatocellular carcinoma (HCC) often have coexisting
      cirrhosis, which may predispose to the development of diabetes mellitus (DM).
      Diabetic HCC patients may have renal insufficiency and a subsequent worse
      outcome. This study investigated the interaction between DM, cirrhosis and renal
      dysfunction and the impact of these factors on HCC. METHODS: A prospective
      database of 1713 HCC patients was analysed. RESULTS: A total of 392 (22.9%)
      patients were diabetic. Diabetic patients had a significantly higher Child
      Turcotte-Pugh (CTP) score, model for end-stage liver disease score and serum
      creatinine level, but had significantly lower serum albumin, sodium, alanine
      aminotransferase, aspartate aminotransferase and bilirubin levels. The serum
      creatinine level progressively increased and correlated well with increasing CTP
      class in both diabetic and non-diabetic patients. After a mean follow-up of 18+/
      16 months, DM was shown to be an independent predictor of mortality in the Cox
      proportional hazard model after adjusting for other predictors [hazard ratio
      (HR): 1.2, 95% confidence interval (CI): 1.02-1.42]. Diabetic patients more often
      had renal insufficiency, defined as serum creatinine>1.5 mg/dl (17.3 vs 8.3%,
      P<0.0001). Renal insufficiency was an independent prognostic predictor in
      diabetic patients (HR: 2.26, 95% CI: 1.57-3.24) but not in non-diabetic patients,
      because it was significantly associated with the severity of cirrhosis in the non
      diabetic group (P<0.001) but not in the diabetic group (P=0.143). CONCLUSIONS: DM
      is associated with inadequate liver reserve and independently predicts decreased
      survival in HCC patients. Both advanced cirrhosis and DM are associated with
      renal insufficiency, which is a poor prognostic predictor for HCC.

PMID- 19849778
TI  - Reconstructing the evolutionary history of nitrotoluene detection in the
      transcriptional regulator NtdR.
AB  - Many toxic man-made compounds have been introduced into the environment, and
      bacterial strains that are able to grow on them are ideal model systems for
      studying the evolution of metabolic pathways and regulatory systems. Acidovorax
      sp. strain JS42 is unique in its ability to use 2-nitrotoluene as a sole carbon,
      nitrogen, and energy source for growth. The LysR-type transcriptional regulator
      NtdR activates expression of the 2-nitrotoluene degradation genes not only when
      nitroaromatic compounds are present, but also in the presence of a wide range of
      aromatic acids and analogues. The molecular determinants of inducer specificity
      were identified through comparative analysis with NagR, the activator of the
      naphthalene degradation pathway genes in Ralstonia sp. strain U2. Although NagR
      is 98% identical to NtdR, it does not respond to nitrotoluenes. Exchange of
      residues that differ between NagR and NtdR revealed that residues at positions
      227 and 232 were key for the recognition of nitroaromatic compounds, while the
      amino acid at position 169 determined the range of aromatic acids recognized.
      Structural modelling of NtdR suggests that these residues are near the predicted
      inducer binding pocket. Based on these results, an evolutionary model is
      presented that depicts the stepwise evolution of NtdR.

PMID- 19849779
TI  - First insights into the genes that control plant-bacterial interactions.
AB  - The events leading up to the cloning of the first bacterial avirulence gene,
      avrA, from Pseudomonas syringae pv. glycinea are described. The cloning of this
      gene marked the beginning of the molecular analyses of bacterial effectors and
      has paved the way for determining of the role of bacterial effectors in pathogen
      virulence and the triggering of plant innate immunity.

PMID- 19849780
TI  - From bacterial avirulence genes to effector functions via the hrp delivery
      system: an overview of 25 years of progress in our understanding of plant innate
      immunity.
AB  - Cloning the first avirulence (avr) gene has led not only to a deeper
      understanding of gene-for-gene interactions in plant disease, but also to
      fundamental insights into the suppression of basal defences against microbial
      attack. This article (focusing on Pseudomonas syringae) charts the development of
      ideas and research progress over the 25 years following the breakthrough achieved
      by Staskawicz and coworkers. Advances in gene cloning technology underpinned the
      identification of both avr and hrp genes, the latter being required for the
      activation of the defensive hypersensitive reaction (HR) and pathogenicity. The
      delivery of Avr proteins through the type III secretion machinery encoded by hrp
      gene clusters was demonstrated, and the activity of the proteins inside plant
      cells as elicitors of the HR was confirmed. Key roles for avr genes in pathogenic
      fitness have now been established. The rebranding of Avr proteins as effectors,
      proteins that suppress the HR and cell wall-based defences, has led to the
      ongoing search for their targets, and is generating new insights into the co
      ordination of plant resistance against diverse microbes. Bioinformatics-led
      analysis of effector gene distribution in genomes has provided a remarkable view
      of the interchange of effectors and also their functional domains, as the arms
      race of attack and defence drives the evolution of microbial pathogenicity. The
      application of our accrued knowledge for the development of disease control
      strategies is considered.

PMID- 19849781
TI  - Fungal effector proteins: past, present and future.
AB  - The pioneering research of Harold Flor on flax and the flax rust fungus
      culminated in his gene-for-gene hypothesis. It took nearly 50 years before the
      first fungal avirulence (Avr) gene in support of his hypothesis was cloned.
      Initially, fungal Avr genes were identified by reverse genetics and map-based
      cloning from model organisms, but, currently, the availability of many sequenced
      fungal genomes allows their cloning from additional fungi by a combination of
      comparative and functional genomics. It is believed that most Avr genes encode
      effectors that facilitate virulence by suppressing pathogen-associated molecular
      pattern-triggered immunity and induce effector-triggered immunity in plants
      containing cognate resistance proteins. In resistant plants, effectors are
      directly or indirectly recognized by cognate resistance proteins that reside
      either on the plasma membrane or inside the plant cell. Indirect recognition of
      an effector (also known as the guard model) implies that the virulence target of
      an effector in the host (the guardee) is guarded by the resistance protein (the
      guard) that senses manipulation of the guardee, leading to activation of effector
      triggered immunity. In this article, we review the literature on fungal effectors
      and some pathogen-associated molecular patterns, including those of some fungi
      for which no gene-for-gene relationship has been established.

PMID- 19849782
TI  - The type III effectors of Xanthomonas.
AB  - A review of type III effectors (T3 effectors) from strains of Xanthomonas reveals
      a growing list of candidate and known effectors based on functional assays and
      sequence and structural similarity searches of genomic data. We propose that the
      effectors and suspected effectors should be distributed into 39 so-called Xop
      groups reflecting sequence similarity. Some groups have structural motifs for
      putative enzymatic functions, and recent studies have provided considerable
      insight into the interaction with host factors in their function as mediators of
      virulence and elicitors of resistance for a few specific T3 effectors. Many
      groups are related to T3 effectors of plant and animal pathogenic bacteria, and
      several groups appear to have been exploited primarily by Xanthomonas species
      based on available data. At the same time, a relatively large number of candidate
      effectors remain to be examined in more detail with regard to their function
      within host cells.

PMID- 19849783
TI  - The evolution of Pseudomonas syringae host specificity and type III effector
      repertoires.
AB  - The discovery 45 years ago that many Pseudomonas syringae pathovars elicit the
      hypersensitive response in plant species other than their hosts fostered the use
      of these bacteria as experimental models. However, the basis for host specificity
      and the corresponding resistance of nonhosts remain unclear. Pseudomonas syringae
      is now known to inject into the host cytoplasm, via the type III secretion
      system, effector proteins that suppress basal innate immunity, but may be
      recognized by cognate resistance (R) proteins in a second level of defence. The
      identification and manipulation of complete repertoires of type III effectors
      have revealed the highly polymorphic nature of effector repertoires and their
      potential to limit the host range. However, the maintenance of compatible
      effector repertoires may be driven by adaptations to life in a given plant
      species involving many factors. Tools are now available to test several
      hypotheses for the nature and evolution of P. syringae host specificity and
      nonhost resistance.

PMID- 19849784
TI  - Advances in experimental methods for the elucidation of Pseudomonas syringae
      effector function with a focus on AvrPtoB.
AB  - Pseudomonas syringae infects a wide range of plant species through the use of a
      type III secretion system. The effector proteins injected into the plant cell
      through this molecular syringe serve as promoters of disease by subverting the
      plant immune response to the benefit of the bacteria in the intercellular space.
      The targets and activities of a subset of effectors have been elucidated
      recently. In this article, we focus on the experimental approaches that have
      proved most successful in probing the molecular basis of effectors, ranging from
      loss-of-function to gain-of-function analyses utilizing several techniques for
      effector delivery into plants. In particular, we highlight how these diverse
      approaches have been applied to the study of one effector--AvrPtoB--a
      multifunctional protein with the ability to suppress both effector-triggered
      immunity and pathogen (or microbe)-associated molecular pattern-triggered
      immunity. Taken together, advances in this field illustrate the need for multiple
      experimental approaches when elucidating the function of a single effector.

PMID- 19849785
TI  - Ten things to know about oomycete effectors.
AB  - Long considered intractable organisms by fungal genetic research standards, the
      oomycetes have recently moved to the centre stage of research on plant-microbe
      interactions. Recent work on oomycete effector evolution, trafficking and
      function has led to major conceptual advances in the science of plant pathology.
      In this review, we provide a historical perspective on oomycete genetic research
      and summarize the state of the art in effector biology of plant pathogenic
      oomycetes by describing what we consider to be the 10 most important concepts
      about oomycete effectors.

PMID- 19849787
TI  - Identification and functional characterization of effectors in expressed sequence
      tags from various life cycle stages of the potato cyst nematode Globodera
      pallida.
AB  - In this article, we describe the analysis of over 9000 expressed sequence tags
      (ESTs) from cDNA libraries obtained from various life cycle stages of Globodera
      pallida. We have identified over 50 G. pallida effectors from this dataset using
      bioinformatics analysis, by screening clones in order to identify secreted
      proteins up-regulated after the onset of parasitism and using in situ
      hybridization to confirm the expression in pharyngeal gland cells. A substantial
      gene family encoding G. pallida SPRYSEC proteins has been identified. The
      expression of these genes is restricted to the dorsal pharyngeal gland cell.
      Different members of the SPRYSEC family of proteins from G. pallida show
      different subcellular localization patterns in plants, with some localized to the
      cytoplasm and others to the nucleus and nucleolus. Differences in subcellular
      localization may reflect diverse functional roles for each individual protein or,
      more likely, variety in the compartmentalization of plant proteins targeted by
      the nematode. Our data are therefore consistent with the suggestion that the
      SPRYSEC proteins suppress host defences, as suggested previously, and that they
      achieve this through interaction with a range of host targets.

PMID- 19849786
TI  - Roadmap for future research on plant pathogen effectors.
AB  - Bacterial and eukaryotic plant pathogens deliver effector proteins into plant
      cells to promote pathogenesis. Bacterial pathogens containing type III protein
      secretion systems are known to inject many of these effectors into plant cells.
      More recently, oomycete pathogens have been shown to possess a large family of
      effectors containing the RXLR motif, and many effectors are also being discovered
      in fungal pathogens. Although effector activities are largely unknown, at least a
      subset suppress plant immunity. A plethora of new plant pathogen genomes that
      will soon be available thanks to next-generation sequencing technologies will
      allow the identification of many more effectors. This article summarizes the key
      approaches used to identify plant pathogen effectors, many of which will continue
      to be useful for future effector discovery. Thus, it can be viewed as a 'roadmap'
      for effector and effector target identification. Because effectors can be used as
      tools to elucidate components of innate immunity, advances in our understanding
      of effectors and their targets should lead to improvements in agriculture.

PMID- 19849788
TI  - Transcription activator-like type III effector AvrXa27 depends on OsTFIIAgamma5
      for the activation of Xa27 transcription in rice that triggers disease resistance
      to Xanthomonas oryzae pv. oryzae.
AB  - The transcription activator-like (TAL) type III effector AvrXa27 from Xanthomonas
      oryzae pv. oryzae (Xoo) strain PXO99(A) activates the transcription of the host
      resistance gene Xa27, which results in disease resistance to bacterial blight
      (BB) in rice. In this study, we show that AvrXa27-activated Xa27 transcription
      requires host general transcription factor OsTFIIAgamma5. The V39E substitution
      in OsTFIIAgamma5, encoded by the recessive resistance gene xa5 in rice, greatly
      attenuates this activation in xa5 and Xa27 double homozygotes on inoculation with
      Xa27-incompatible strains. The xa5 gene also causes attenuation in the induction
      of Xa27 by AvrXa27 expressed in rice. The xa5-mediated attenuation of Xa27
      mediated resistance to PXO99(A) is recessive. Intriguingly, xa5-mediated
      resistance to xa5-incompatible strains is also down-regulated in the xa5 and Xa27
      double homozygotes. In addition, AvrXa27 expressed in planta shows weak virulence
      activity in the xa5 genetic background and causes enhanced susceptibility of the
      plants to BB inoculation. The results suggest that TAL effectors target host
      general transcription factors to directly manipulate the host transcriptional
      machinery for virulence and/or avirulence. The identification of xa5-mediated
      attenuation of Xa27-mediated resistance to Xoo provides a guideline for breeding
      resistance to BB when pyramiding xa5 with other resistance genes.

PMID- 19849789
TI  - Contributions of the effector gene hopQ1-1 to differences in host range between
      Pseudomonas syringae pv. phaseolicola and P. syringae pv. tabaci.
AB  - To study the role of type III-secreted effectors in the host adaptation of the
      tobacco (Nicotiana sp.) pathogen Pseudomonas syringae pv. tabaci, a selection of
      seven strains was first characterized by multilocus sequence typing (MLST) to
      determine their phylogenetic affinity. MLST revealed that all strains represented
      a tight phylogenetic group and that the most closely related strain with a
      completely sequenced genome was the bean (Phaseolus vulgaris) pathogen P.
      syringae pv. phaseolicola 1448A. Using primers designed to 21 P. syringae pv.
      phaseolicola 1448A effector genes, it was determined that P. syringae pv.
      phaseolicola 1448A shared at least 10 effectors with all tested P. syringae pv.
      tabaci strains. Six of the 11 effectors that failed to amplify from P. syringae
      pv. tabaci strains were individually expressed in one P. syringae pv. tabaci
      strain. Although five effectors had no effect on phenotype, growth in planta and
      disease severity of the transgenic P. syringae pv. tabaci expressing hopQ1
      1(Pph1448A) were significantly increased in bean, but reduced in tobacco. We
      conclude that hopQ1-1 has been retained in P. syringae pv. phaseolicola 1448A, as
      this effector suppresses immunity in bean, whereas hopQ1-1 is missing from P.
      syringae pv. tabaci strains because it triggers defences in Nicotiana spp. This
      provides evidence that fine-tuning effector repertoires during host adaptation
      lead to a concomitant reduction in virulence in non-host species.

PMID- 19849790
TI  - Metabolic adaptation of Phytophthora infestans during growth on leaves, tubers
      and artificial media.
AB  - Efficient nutrient acquisition is critical to the fitness of plant pathogens. To
      address how the late blight agent Phytophthora infestans adapts to nutrients
      offered by its hosts, genes in glycolytic, gluconeogenic and amino acid pathways
      were mined from its genome and their expression in different plant tissues and
      artificial media was measured. Evidence for conventional glycolytic and
      gluconeogenic processes was obtained, although several steps involved
      pyrophosphate-linked transformations which are uncommon in eukaryotes. In media
      manipulation studies, nearly all genes in the pathways were subject to strong
      transcriptional control. However in rye-sucrose media, tomato leaflets, potato
      tubers and, at both early and late stages of infection, most glycolytic genes
      were expressed similarly, which indicated that each plant tissue presented a
      nutrient-rich environment. Biochemical analyses also demonstrated that
      sporulation occurred from host material in which sugars were abundant, with
      fructose and glucose increasing at the expense of sucrose late in the disease
      cycle. The expression of only a few genes changed late in infection, with the
      most notable example being lower invertase levels in the sucrose-reduced leaves.
      Interestingly, most gluconeogenic genes were up-regulated in tubers compared with
      other tissues. Rather than reflecting a starvation response, this probably
      reveals the role of such enzymes in converting carbon skeletons from the abundant
      free amino acids of tubers into citric acid cycle and glycolysis intermediates,
      as genes involved in amino acid catabolism were also more highly expressed in
      tubers. The corresponding enzymes also displayed higher activities in defined
      media when amino acids were abundant, as in tubers.

PMID- 19849791
TI  - Pseudomonas syringae pv. syringae B728a hydrolyses indole-3-acetonitrile to the
      plant hormone indole-3-acetic acid.
AB  - Nitrilase enzymes catalyse the hydrolysis of nitrile compounds to the
      corresponding carboxylic acid and ammonia, and have been identified in plants,
      bacteria and fungi. There is mounting evidence to support a role for nitrilases
      in plant-microbe interactions, but the activity of these enzymes in plant
      pathogenic bacteria remains unexplored. The genomes of the plant pathogenic
      bacteria Pseudomonas syringae pv. syringae B728a and Pseudomonas syringae pv.
      tomato DC3000 contain nitrilase genes with high similarity to characterized
      bacterial arylacetonitrilases. In this study, we show that the nitrilase of P.
      syringae pv. syringae B728a is an arylacetonitrilase, which is capable of
      hydrolysing indole-3-acetonitrile to the plant hormone indole-3-acetic acid, and
      allows P. syringae pv. syringae B728a to use indole-3-acetonitrile as a nitrogen
      source. This enzyme may represent an additional mechanism for indole-3-acetic
      acid biosynthesis by P. syringae pv. syringae B728a, or may be used to degrade
      and assimilate aldoximes and nitriles produced during plant secondary metabolism.
      Nitrilase activity was not detected in P. syringae pv. tomato DC3000, despite the
      presence of a homologous nitrilase gene. This raises the interesting question of
      why nitrilase activity has been retained in P. syringae pv. syringae B728a and
      not in P. syringae pv. tomato DC3000.

PMID- 19849793
TI  - Brain pathology in three subjects from the same pedigree with presenilin-1
      (PSEN1) P264L mutation.
AB  - AIMS: Our goal was to assess pathological lesions with respect to type and
      distribution and to compare these results with the clinical presentation
      including symptoms and mode of progression in three members of the same pedigree
      with a P264L presenilin-1 gene mutation. METHODS: We used immunohistochemistry
      and a tissue microarray technique applied to post mortem brain tissue samples.
      RESULTS: All three subjects were demented, one subject displayed spastic
      paraparesis and two had Parkinsonism. All three cases displayed abundant cotton
      wool plaques composed of amyloid-beta42 but also containing other proteins, for
      example, hyperphosphorylated tau and in one case TAR DNA binding protein 43. The
      distribution of the pathology varied and seemed to some extent to be related to
      the clinical phenotype. An association was detected between neocortical/thalamic
      involvement and psychiatric symptoms, between striatal/amygdaloid involvement and
      Parkinsonism, and between brainstem involvement and spastic paraparesis.
      CONCLUSIONS: Subjects from the same pedigree carrying the same mutation display a
      clear variability in the type and distribution of pathology as well as in their
      clinical symptoms. These results emphasize that still unknown factors
      significantly alter the pathological and clinical phenotypes in genetically
      predetermined disease.

PMID- 19849792
TI  - The c-Jun N-terminal kinase (JNK) inhibitor XG-102 enhances the neuroprotection
      of hyperbaric oxygen after cerebral ischaemia in adult rats.
AB  - AIM: Both hyperbaric oxygenation (HBO) and inhibition of the c-Jun N-terminal
      kinases (JNKs) by the peptide inhibitor XG-102 (D-JNKI-1) are efficient
      protective strategies against ischaemia-induced neurodegeneration. The present
      study investigated whether the combination of HBO and JNK inhibitor, XG-102,
      provides additive neuroprotection against cerebral ischaemia. METHODS: Rat middle
      cerebral artery was occluded (MCAO) for 90 min. XG-102 [2 mg/kg,
      intraperitoneally] or HBO (3 ATA, 60 min) was applied 3 h after the onset of
      MCAO. For the combination treatment, HBO was started 10 min after the injection
      of XG-102. Twenty-four hours after MCAO, the infarct area, the neurological score
      and the immunohistochemistry staining in brain slices for cleaved-PARP,
      transferase-mediated biotinylated UTP nick end labelling, c-Jun and
      phosphorylated (activated) c-Jun were observed. RESULTS: XG-102 or HBO alone
      reduced the total infarct area by 43% and 63%, respectively. The combination
      diminished total infarct area by 78%, improved the neurological function and
      reduced brain oedema. Co-application of HBO and XG-102 also significantly reduced
      the cleavage of PARP, by 96% and 91% in cortical penumbra and ischaemic core,
      respectively. Moreover, cotreatment significantly attenuated the number of cells
      labelled with transferase-mediated biotinylated UTP nick end labelling and
      phosphorylated c-Jun. CONCLUSION: Our study demonstrates that HBO reinforces the
      efficiency of neuroprotective drugs such as XG-102 and vice versa. Both
      treatments, physical HBO and pharmacological XG-102, are already in phase I/II
      studies and promising strategies for clinical use.

PMID- 19849794
TI  - Commentary: On the possible links between tree growth and galactic cosmic rays.

PMID- 19849795
TI  - Missing links in the root-soil organic matter continuum.

PMID- 19849796
TI  - Circadian biology and sleep: missing links in obesity and metabolism?
AB  - This supplement highlights key talks presented at the Pennington Symposium. The
      collected papers provide a state of the art review of circadian biology at the
      basic and clinical levels in the context of nutrition, obesity and sleep
      medicine. Investigators from multiple disciplines attempted to translate new
      information concerning molecular mechanisms into practical clinical applications,
      as well as foster new research hypotheses and directions to this exciting field
      of science and medicine. Furthermore, we hope to spark the interest and attention
      of the next generation of scientists who will tackle the questions presented by
      the changing interface between technology, lifestyle and biological rhythms.

PMID- 19849797
TI  - The role of cell-specific circadian clocks in metabolism and disease.
AB  - Biological rhythms are an integral component of essentially all aspects of life.
      These rhythms are controlled in part by circadian clocks, transcriptionally based
      mechanisms that synchronize the organism to its changing environment. The central
      circadian clock is located within the suprachiasmatic nucleus of the brain, while
      peripheral clocks are located within virtually all cells outside of the
      suprachiasmatic nucleus. Although our understanding of central clock structure
      and function is well advanced, the role of peripheral clocks in whole body energy
      metabolism is just beginning to be elucidated. Both central and peripheral
      circadian clocks likely regulate many physiological functions, including insulin
      sensitivity, endocrine regulation, energy homeostasis, satiety signalling,
      cellular proliferation and cardiovascular function. Widely varying phenotypes
      have been reported following global genetic disruption of the clock mechanism in
      mice, with phenotype dependent on both the clock component targeted and genetic
      background. The inconsistency in phenotypes associated with clock disruption may
      be due, in part, to cell-specific effects of the circadian clocks. To address
      this question, many laboratories have begun generating animal models of cell type
      specific clock disruption. In this review, we summarize the existing literature
      on tissue-specific models of circadian clock disruption and provide a focus for
      future research in this area.

PMID- 19849799
TI  - The regulation of central and peripheral circadian clocks in humans.
AB  - Many circadian rhythms are controlled by the central clock of the suprachiasmatic
      nucleus of the hypothalamus, as well as clocks located in other brain regions and
      most peripheral tissues. These central and peripheral clocks are based on clock
      genes and their protein products. In recent years, the expression of clock genes
      has started to be investigated in human samples, primarily white blood cells, but
      also skin, oral mucosa, colon cells, adipose tissue as well as post-mortem brain
      tissue. The expression of clock genes in those peripheral tissues offers a way to
      monitor human peripheral clocks and to compare their function and regulation with
      those of the central clock, which is followed by markers such as melatonin,
      cortisol and core body temperature. We have recently used such an approach to
      compare central and peripheral rhythms in subjects under different lighting
      conditions. In particular, we have monitored the entrainment of the clock of
      blood cells in subjects undergoing a simulated night shift protocol with bright
      light treatment, known to efficiently reset the central clock. This line of
      research will be helpful for learning more about the human circadian system and
      to find ways to alleviate health problems of shift workers, and other populations
      experiencing altered circadian rhythms.

PMID- 19849798
TI  - The role of melanocortin neuronal pathways in circadian biology: a new
      homeostatic output involving melanocortin-3 receptors?
AB  - Obesity, insulin resistance and increased propensity for type 2 diabetes and
      cardiovascular disease result from an imbalance between energy intake and
      expenditure. The cloning of genes involved in energy homeostasis produced a
      simple feedback model for the homeostatic regulation of adipose mass. Serum
      leptin secreted from adipocytes signals nutrient sufficiency, curbing appetite
      and supporting energy expenditure. A rapid decline in leptin during nutrient
      scarcity instigates adaptive mechanisms, including increased appetite and reduced
      energy expenditure. Hypothalamic melanocortin neurons are important mediators of
      this response, integrating inputs of energy status from leptin with other
      peripheral signals. While this feedback response prolongs survival during
      fasting, other mechanisms allowing the prediction of nutrient availability also
      confer a selective advantage. This adaptation has been commonly studied in
      rodents using restricted feeding paradigms constraining food intake to limited
      periods at 24-h intervals. Restricted feeding rapidly elicits rhythmic bouts of
      activity and wakefulness anticipating food presentation. While the response
      exhibits features suggesting a clock-like mechanism, the neuromolecular
      mechanisms governing expression of food anticipatory behaviours are poorly
      understood. Here we discuss a model whereby melanocortin neurons regulating the
      homeostatic adaptation to variable caloric availability also regulate inputs into
      neural networks governing anticipatory rhythms in wakefulness, activity and
      metabolism.

PMID- 19849801
TI  - Delta sleep-inducing peptide and glucocorticoid-induced leucine zipper: potential
      links between circadian mechanisms and obesity?
AB  - As the obesity pandemic has accelerated, investigators have begun to explore
      alternative mechanisms linking circadian biology and sleep to adipose tissue
      metabolism and obesity. This manuscript reviews recent findings in murine and
      human models demonstrating the oscillatory expression of the mRNAs encoding the
      core circadian regulatory proteins in adipose tissue. Comparative transcriptomic
      analyses of circadian oscillating genes have been used to identify the 'delta
      sleep-inducing peptide immunoreactor', also known as 'glucocorticoid-induced
      leucine zipper (GILZ)', as a potential link in this chain. The GILZ gene has been
      found to differentially regulate stromal stem cell adipogenic and osteogenic
      differentiation in a reciprocal manner. In adipose and other metabolically active
      tissues, the circadian oscillation of GILZ expression is subject to entrainment
      by external stimuli. Together, these observations suggest that GILZ is an
      attractive candidate for future studies evaluating the role of circadian
      mechanisms in adipose tissue physiology and pathology.

PMID- 19849800
TI  - Epidemiological evidence for the links between sleep, circadian rhythms and
      metabolism.
AB  - Epidemiological data reveal parallel trends of decreasing sleep duration and
      increases in metabolic disorders such as obesity, diabetes and hypertension.
      There is growing evidence that these trends are mechanistically related. The
      seasonal expression of the thrifty genotype provides a conceptual framework to
      connect circadian and circannual rhythms, sleep and metabolism. Experimental
      studies have shown sleep deprivation to decrease leptin, increase ghrelin,
      increase appetite, compromise insulin sensitivity and raise blood pressure.
      Habitually short sleep durations could lead to insulin resistance by increasing
      sympathetic nervous system activity, raising evening cortisol levels and
      decreasing cerebral glucose utilization that over time could compromise beta-cell
      function and lead to diabetes. Prolonged short sleep durations could lead to
      hypertension through raised 24-h blood pressure and increased salt retention
      resulting in structural adaptations and the entrainment of the cardiovascular
      system to operate at an elevated pressure equilibrium. Cross-sectional and
      longitudinal epidemiological studies have shown associations between short sleep
      duration and obesity, diabetes and hypertension. If metabolic changes resulting
      from sleep restriction function to increase body weight, insulin resistance and
      blood pressure then interventions designed to increase the amount and improve the
      quality of sleep could serve as treatments and as primary preventative measures
      for metabolic disorders.

PMID- 19849802
TI  - Adipose tissue, adipocytes and the circadian timing system.
AB  - Circadian clocks time the daily occurrence of multiple aspects of behaviour and
      physiology. Through studies of chronic misalignment between our internal clocks
      and the environment (e.g. during shift work), it has long been postulated that
      disruption of circadian rhythms is detrimental to human health. Recent advances
      in understanding of the cellular and molecular basis of mammalian circadian
      timing mechanisms have identified many key genes involved in circadian rhythm
      generation and demonstrated the presence of clocks throughout the body.
      Furthermore, clear links between sleep, circadian rhythms and metabolic function
      have been revealed, and much current research is studying these links in more
      detail. Here, we review the evidence linking circadian rhythms, clock genes and
      adipose biology. We also highlight gaps in our understanding and finally suggest
      avenues for future research.

PMID- 19849803
TI  - Reduced sleep as an obesity risk factor.
AB  - Poor sleep has increasingly gained attention as a potential contributor to the
      recent obesity epidemic. The increased prevalence of obesity in Western nations
      over the past half-century has been paralleled by a severe reduction in sleep
      duration. Physiological studies suggest reduced sleep may impact hormonal
      regulation of appetite. Prospective studies suggest reduced habitual sleep
      duration as assessed by self-report is an independent risk factor for an
      increased rate of weight gain and incident obesity. Cross-sectional studies have
      demonstrated that the association between reduced sleep and obesity persists when
      sleep habits are measured objectively, that the association is as a result of
      elevations in fat and not muscle mass and that this association is not related to
      sleep apnoea. Thus, reduced sleep appears to represent a novel, independent risk
      factor for increased weight gain. Further research is needed to determine whether
      interventions aimed at increasing sleep may be useful in combating obesity.

PMID- 19849804
TI  - A biobehavioural model of the night eating syndrome.
AB  - This paper will propose a biobehavioral mechanism for the Night Eating Syndrome
      (NES), a disorder characterized by a delayed circadian rhythm of food intake and
      neuroendocrine function. Food intake consists of at least 25% of daily caloric
      intake after the evening meal and/or at least two nighttime awakenings with
      ingestions per week. This will be explored by reviewing neuroimaging of brain
      serotonin transporters (SERT) and treatment with selective serotonin reuptake
      inhibitors (SSRIs). SERT binding is elevated in the midbrain of night eaters,
      causing dysregulation of the circadian rhythm of both food intake and
      neuroendocrine function. The administration of SSRIs blocks the reuptake of
      serotonin and restores the circadian rhythm of both food intake and
      neuroendocrine function. This hypothesis implies that reduction of SERT activity
      should increase postsynaptic serotonin transmission and relieve NES. This is
      precisely the effect of SSRIs. NES is a function of elevated SERT, and blocking
      of SERT with an SSRI resolves NES. This model of NES attests to the validity of
      the diagnosis of NES and the criteria by which it is identified, and it provides
      an explanation of the mechanism.

PMID- 19849805
TI  - Confounding and interaction effect of Treponema denticola salivary carriage in
      chronic periodontitis.
AB  - AIM: To evaluate the salivary carriage of Treponema denticola and its association
      with demographic variables in the etiopathogenesis of chronic periodontitis.
      SUBJECTS AND METHODS: Ninety-seven chronic periodontitis (CP) patients and a
      control group of 51 healthy subjects (HC) were selected. Periodontal status was
      assessed by criteria based on probing depth, attachment loss, extent, and
      severity of periodontal breakdown. A polymerase chain reaction method was used to
      determine the occurrence of T. denticola in saliva samples. Risk indicators for
      CP were assessed individually and adjusted for confounding and/or interaction
      using a logistic regression model. RESULTS: Although univariate analysis revealed
      a positive association of age >or=30 years, smoking, and salivary carriage of T.
      denticola with CP, after logistic regression analysis, the association between
      age >or=30 years/smoking and CP persisted, whereas salivary carriage of T.
      denticola failed to achieve statistical significance. An interaction effect was
      significantly detected between these three variables. CONCLUSION: Although
      salivary carriage of T. denticola may be a risk indicator for CP, its
      pathogenicity should not be exclusively endorsed to its detection in saliva, but
      it might be associated with the synergistic biological interaction of the
      bacterium with some demographic characteristics of the susceptible host.

PMID- 19849806
TI  - Prenatal and neonatal risk factors for the development of enamel defects in low
      birth weight children.
AB  - OBJECTIVE: To analyse the influence of several prenatal and neonatal risk factors
      in the development of enamel defects in low birth weight children. SUBJECTS AND
      METHODS: Children between 4 and 5 years of age (n = 102) were classified into:
      Group 1) 52 low birth weight (<2500 g); Group 2) 50 normal birth weight (>or=2500
      g). Medical history, prenatal and neonatal variables were collected. Enamel
      defects were evaluated with the modified Developmental Defects of Enamel Index.
      RESULTS: The prevalence of hypoplasia and average number of affected teeth were
      significantly higher in group 1 than in group 2 (59.6%vs 16% and 1.6 vs 0.3
      respectively). Low gestational age was linked to a higher prevalence of
      hypoplastic (P = 0.027) and combined defects (P = 0.001). Children with neonatal
      risk factors (low Apgar scores, parenteral nutrition, orotracheal intubation,
      mechanical ventilation and acidosis) developed defects more frequently (P <
      0.05). Defects were symmetrically distributed in children who were not intubated;
      in those who required intubation they concentrated on the left maxillary teeth (P
      < 0.05). Smoking during pregnancy, young maternal age and multiple birth were
      significantly associated to developmental defects. CONCLUSIONS: The prevalence of
      enamel defects in primary dentition is significantly influenced by birth weight,
      gestational age and several systemic factors. Orotracheal intubation probably
      plays an important role as a result of laryngoscope trauma on the maxilla.

PMID- 19849807
TI  - Extended experience with a steroid minimization immunosuppression protocol in
      pediatric renal transplant recipients.
AB  - PURPOSE: To determine the safety and efficacy of a novel steroid minimization
      protocol after renal transplantation at a single Northern California center.
      INTRODUCTION: We have previously reported our experience on the short-term
      outcomes in eight children using our steroid minimization protocol. Herein, we
      present our ongoing experience in using this regimen in 20 children. METHODS:
      Children receiving immunosuppression with a steroid minimization protocol at our
      center from 1/04-12/08 (Group 2) were retrospectively compared with 20 controls
      (Group 1). RESULTS: At one-month follow-up, Group 2 was observed to have lower
      eGFR, hemoglobin, white cell count, and cholesterol. The incidence of adverse
      events during the first yr was comparable. Three patients in Group 1 displayed
      histological evidence of acute rejection, one patient in Group 2 developed
      humoral rejection; another patient in Group 2 had sub-clinical rejection.
      Surgical complications were observed in 20% of patients in both groups. While 10%
      of patients in Group 1 developed diabetes mellitus, none was observed in Group 2.
      Thirty and 40% of patients in Groups 1 and 2, respectively, suffered from
      infectious complications during the first yr. CONCLUSIONS: Our novel steroid
      minimization immunosuppression is safe in children and associated with no
      increased risk of rejection and infection.

PMID- 19849808
TI  - Thrombotic events after pediatric liver transplantation.
AB  - TE may contribute to morbidity and mortality after LT. The objectives were to
      determine the incidence of early TE post-pediatric LT and compare differences
      between children with and without TE. A retrospective review of 88 transplanted
      children (January 2002-October 2007) was performed to determine the incidence of
      Doppler-confirmed DVT and ATE in the first month post-LT. Fourteen (16%) patients
      developed TE: DVT in seven (8%) and ATE in seven (8%) patients. Six of 88 (6.8%)
      developed symptomatic CVL-related DVT. Median (range) time post-LT to DVT and ATE
      were 7 (4-18) and 8 (1-31) days, respectively. There was no significant
      difference in age/body weight at LT between patients with or without DVT and ATE.
      There was no significant difference between patients with or without HAT in age
      and weight at LT, cold ischemic time, duration of surgery, hematocrit levels,
      whole-organ graft type, intraoperative FFP, high-risk CMV status, or early acute
      cellular rejection. In conclusion, the incidence of early TE post-pediatric LT
      was 16%, including DVT in 8%. Prospective studies are necessary to evaluate the
      role of prophylactic anticoagulation and potential modifiable risk factors post
      pediatric LT.

PMID- 19849809
TI  - Successful unrelated donor cord blood transplantation for Glanzmann's
      thrombasthenia.
AB  - GT, a rare disorder of platelet function, can lead to life-threatening bleeding,
      particularly following the development of antiplatelet antibodies. Curative
      therapy includes HCT but previous reports are limited predominantly to matched
      siblings and have excluded CBT. Delayed or non-engraftment of platelets because
      of antiplatelet antibodies might be particularly concerning after CBT for GT.
      Here, we report two successful unrelated cord blood transplants for GT. Recurrent
      life-threatening bleeding was the primary indication for HCT, with one patient
      developing antiplatelet antibodies pre-HCT. Bleeding risks associated with
      delivery of the conditioning regimen and the toxicity that follows should be
      carefully considered, including tunneled central venous line catheter placement,
      inclusion of B cell-specific therapy to potentially decrease antiplatelet
      antibody production, and targeted busulfan dosing. This is the first report of
      successful unrelated cord blood HCT for GT and indicates that modifications to
      supportive care can improve the safety of this potentially curative therapy for
      patients with severe, life-threatening disease manifestations.

PMID- 19849810
TI  - Gender differences in asthma prevalence: variations with socioeconomic
      disadvantage.
AB  - BACKGROUND AND OBJECTIVE: Socioeconomic inequalities in health have been shown to
      vary for different diseases and by gender. This study aimed to examine gender
      differences in associations between asthma and socioeconomic disadvantage.
      METHODS: Socioeconomic variables were assessed among men and women in the North
      West Adelaide Health Study, a representative population cohort (n = 4060) aged 18
      years and over in metropolitan South Australia. Asthma was determined from
      spirometry and self-reported doctor diagnosis. RESULTS: The prevalence of asthma
      was 12.0% (95% CI: 11.1-13.1), and was significantly higher among women (13.5%)
      than men (10.5%). For participants aged 18-64 years a higher prevalence of asthma
      was associated with an education level of secondary school or lower, or not being
      in the paid labour force among men, and with a gross annual household income of
      $20,000 or less among women. Among socioeconomically advantaged groups, the
      prevalence of asthma was significantly higher among women than men. CONCLUSIONS:
      Socioeconomic disadvantage was associated with higher asthma prevalence, although
      this varied by gender depending on the indicator of socioeconomic position used.
      Men with low education or those not employed in the paid labour force had higher
      asthma prevalence than more socioeconomically advantaged men. Women with low
      income had higher asthma prevalence than those with higher income. Among all
      socioeconomically advantaged groups, and also the low-income group, women
      experienced a higher prevalence of asthma than men.

PMID- 19849811
TI  - Living on the edge. Abstracts of the Australasian Professional Society on Alcohol
      and other Drugs Conference 2009. November 1-4, 2009. Darwin, Australia.

PMID- 19849812
TI  - Inactivation of food pathogen Bacillus cereus by photosensitization in vitro and
      on the surface of packaging material.
AB  - AIMS: The study was focused on the possibility to inactivate food pathogen
      Bacillus cereus by 5-aminolevulinic acid (ALA) - based photosensitization in
      vitro and after adhesion on the surface of packaging material. METHODS AND
      RESULTS: Bacillus cereus was incubated with ALA (3-7.5 mmol l(-1)) for 5-60 min
      in different environment (PBS, packaging material and wheat grains) and
      afterwards illuminated with visible light. The light source used for illumination
      emitted light at lambda = 400 nm with energy density at the position of the
      cells, 20 mW cm(-2). The illumination time varied from 0 to 20 min, and
      subsequently a total energy dose was between 0 and 24 J cm(-2). The obtained
      results indicate that B. cereus after the incubation with 3-7.5 mmol l(-1) ALA
      produces suitable amounts of endogenous photosensitizers. Following illumination,
      micro-organism inactivated even by 6.3 log. The inactivation of B. cereus after
      adhesion on the surface of food packaging by photosensitization reached 4 log. It
      is important to note that spores of B. cereus were susceptible to this treatment
      as well; 3.7-log inactivation in vitro and 2.7-log inactivation on the surface of
      packaging material were achieved at certain experimental conditions. CONCLUSIONS:
      Vegetative cells and spores of Gram-positive food pathogen B. cereus were
      effectively inactivated by ALA-based photosensitization in vitro. Moreover, the
      significant inactivation of B. cereus adhered on the surface of packaging
      material was observed. It was shown that photosensitization-based inactivation of
      B. cereus depended on the total light dose (illumination time) as well as on the
      amount of endogenous porphyrins (initial ALA concentration, time of incubation
      with ALA). SIGNIFICANCE AND IMPACT OF THE STUDY: Our previous data, as well as
      the one obtained in this study, support the idea that photosensitization with its
      high selectivity, antimicrobial efficiency and nonthermal nature could serve in
      the future for the development of completely safe, nonthermal surface
      decontamination and food preservation techniques.

PMID- 19849813
TI  - Abstracts of AIDS Vaccine 2009. Paris, France. October 19-22, 2009.

PMID- 19849814
TI  - Key signalling nodes in mammary gland development and cancer: Myc.
AB  - Myc has been intensely studied since its discovery more than 25 years ago.
      Insight has been gained into Myc's function in normal physiology, where its role
      appears to be organ specific, and in cancer where many mechanisms contribute to
      aberrant Myc expression. Numerous signals and pathways converge on Myc, which in
      turn acts on a continuously growing number of identified targets, via
      transcriptional and nontranscriptional mechanisms. This review will concentrate
      on Myc as a signaling mediator in the mammary gland, discussing its regulation
      and function during normal development, as well as its activation and roles in
      breast cancer.

PMID- 19849815
TI  - Notch versus the proteasome: what is the target of gamma-secretase inhibitor-I?
AB  - gamma-Secretase inhibitors are new anti-cancer agents targeting Notch signaling.
      Their specificity for Notch is as yet unclear. Han and colleagues investigated
      the effects of Z-LeuLeuNleu-CHO on growth of breast cancer cells. The results
      demonstrated a reduction in cell viability primarily via proteasome inhibition
      independent of Notch activity. Currently, gamma-secretase inhibitors in clinical
      trials are structurally distinct from Z-LeuLeuNleu-CHO. Their effects on the
      proteasome are yet to be determined. However, findings from Han and colleagues
      pose two critical questions: Is the level of proteasomal activity in breast
      tumors the driving force for growth? What does the Notch pathway contribute to
      this growth?

PMID- 19849816
TI  - Genetics of rheumatic disease.
AB  - Many of the chronic inflammatory and degenerative disorders that present to
      clinical rheumatologists have a complex genetic aetiology. Over the past decade a
      dramatic improvement in technology and methodology has accelerated the pace of
      gene discovery in complex disorders in an exponential fashion. In this review, we
      focus on rheumatoid arthritis, systemic lupus erythematosus and ankylosing
      spondylitis and describe some of the recently described genes that underlie these
      conditions and the extent to which they overlap. The next decade will witness a
      full account of the main disease susceptibility genes in these diseases and
      progress in establishing the molecular basis by which genetic variation
      contributes to pathogenesis.

PMID- 19849817
TI  - Developments in the clinical understanding of lupus.
AB  - Advances in genetics and new understanding of the molecular pathways that mediate
      innate and adaptive immune system activation, along with renewed focus on the
      role of the complement system as a mediator of inflammation, have stimulated
      elaboration of a scheme that might explain key mechanisms in the pathogenesis of
      systemic lupus erythematosus. Clinical observations identifying important
      comorbidities in patients with lupus have been a recent focus of research linking
      immune mechanisms with clinical manifestations of disease. While these advances
      have identified rational and promising targets for therapy, so far the
      therapeutic trials of new biologic agents have not met their potential.
      Nonetheless, progress in understanding the underlying immunopathogenesis of lupus
      and its impact on clinical disease has accelerated the pace of clinical research
      to improve the outcomes of patients with systemic lupus erythematosus.

PMID- 19849818
TI  - Brachial artery flow velocity variation: another victory for hand-carried
      ultrasound?
AB  - Dynamic predictors are clearly superior to static pressures in predicting whether
      a patient will respond to a fluid bolus. Hand-carried ultrasound (HCUS) can
      measure changes in blood flow velocity in the brachial artery that parallel
      arterial pulse pressure variation. The potential for HCUS to guide fluid therapy
      non-invasively must overcome problems of sensitivity and applicability.

PMID- 19849820
TI  - B cells in autoimmunity.
AB  - B-cell development is tightly regulated, including the induction of B-cell memory
      and antibody-secreting plasmablasts and plasma cells. In the last decade, we have
      expanded our understanding of effector functions of B cells as well as their
      roles in human autoimmune diseases. The current review addresses the role of
      certain stages of B-cell development as well as plasmablasts/plasma cells in
      immune regulation under normal and autoimmune conditions with particular emphasis
      on systemic lupus erythematosus. Based on preclinical and clinical data, B cells
      have emerged increasingly as both effector cells as well as cells with
      immunoregulatory potential.

PMID- 19849821
TI  - Outcome measures in inflammatory rheumatic diseases.
AB  - Inflammatory rheumatic diseases are generally multifaceted disorders and,
      therefore, measurement of multiple outcomes is relevant to most of these
      diseases. Developments in outcome measures in the rheumatic diseases are promoted
      by the development of successful treatments. Outcome measurement will
      increasingly deal with measurement of low levels of disease activity and
      avoidance of disease consequences. It is an advantage for patient management and
      knowledge transfer if the same outcomes are used in practice and in trials.
      Continuous measures of change are generally the most powerful and, therefore, are
      preferred as primary outcomes in trials. For daily clinical practice, outcome
      measures should reflect the patients' state and have to be easily derivable. The
      objective of this review is to describe recent developments in outcome measures
      for inflammatory rheumatic diseases for trials and clinical practice, with an
      emphasis on rheumatoid arthritis.

PMID- 19849819
TI  - Progress in osteoporosis and fracture prevention: focus on postmenopausal women.
AB  - In the past decade, we have witnessed a revolution in osteoporosis diagnosis and
      therapeutics. This includes enhanced understanding of basic bone biology,
      recognizing the severe consequences of fractures in terms of morbidity and short
      term re-fracture and mortality risk and case finding based on clinical risks,
      bone mineral density, new imaging approaches, and contributors to secondary
      osteoporosis. Medical interventions that reduce fracture risk include sufficient
      calcium and vitamin D together with a wide spectrum of drug therapies (with
      antiresorptive, anabolic, or mixed effects). Emerging therapeutic options that
      target molecules of bone metabolism indicate that the next decade should offer
      even greater promise for further improving our diagnostic and treatment
      approaches.

PMID- 19849822
TI  - Lessons from animal models of arthritis over the past decade.
AB  - This review summarizes the major developments in animal models of arthritis in
      the past decade. It focuses on novel transgenic models, addresses the involvement
      of cytokines and discusses novel findings in cartilage and bone erosion. It is
      clear that interest has been raised in the direct arthritogenic role of
      autoantibodies, apart from T cell involvement, and their interaction with cells
      through Fcgamma receptors. In addition, a role for IL-6 and IL-17 and Th17 cells
      seems apparent in most T cell-driven arthritis models, with environmental
      triggering through Toll-like receptors contributing to this process. Further
      insights into enzymes involved in cartilage proteoglycan loss in arthritis, as
      well as mediators regulating bone erosion and bone apposition, have been gained.

PMID- 19849823
TI  - Cytokines in chronic rheumatic diseases: is everything lack of homeostatic
      balance?
AB  - Biological systems have powerful inbuilt mechanisms of control intended to
      maintain homeostasis. Cytokines are no exception to this rule, and imbalance in
      cytokine activities may lead to inflammation with subsequent tissue and organ
      damage, altered function, and death. Balance is achieved through multiple, not
      mutually exclusive, mechanisms including the simultaneous production of agonist
      and antagonistic cytokines, expression of soluble receptors or membrane-bound
      nonsignaling receptors, priming and/or reprogramming of signaling, and uncoupling
      of ligand/receptor pairing from signal transduction. Insight into cytokine
      balance is leading to novel therapeutic approaches particularly in autoimmune
      conditions, which are intimately linked to a dysregulated cytokine production.

PMID- 19849825
TI  - The paradox of ventilator-associated pneumonia prevention measures.
AB  - There is a striking paradox in the literature supporting high-profile measures to
      reduce ventilator-associated pneumonia (VAP): many studies show significant
      reductions in VAP rates but almost none show any impact on patients' duration of
      mechanical ventilation, length of stay in the intensive care unit and hospital,
      or mortality. The paradox is largely attributable to lack of specificity in the
      VAP definition. The clinical and microbiological criteria for VAP capture a
      population of patients with an array of conditions that range from serious to
      benign. Many of the benign events are manifestations of bacterial colonization
      superimposed upon pulmonary edema, atelectasis, or other non-infectious
      processes. VAP prevention measures that work by decreasing bacterial colonization
      preferentially lower the frequency of these mislabelled, more benign events. In
      addition, misclassification obscures detection of an impact of prevention
      measures on bona fide pneumonias. Together, these effects create the possibility
      of the paradox where a prevention measure may have a large impact on VAP rates
      but minimal impact on patients' outcomes. The paradox makes changes in VAP rates
      alone an unreliable measure of whether VAP prevention measures are truly
      beneficial to patients and behooves us to measure their impact on patient
      outcomes before advocating their adoption.

PMID- 19849826
TI  - Severe community acquired pneumonia: what should we predict?

PMID- 19849827
TI  - Health technology assessment review: Computerized glucose regulation in the
      intensive care unit--how to create artificial control.
AB  - Current care guidelines recommend glucose control (GC) in critically ill
      patients. To achieve GC, many ICUs have implemented a (nurse-based) protocol on
      paper. However, such protocols are often complex, time-consuming, and can cause
      iatrogenic hypoglycemia. Computerized glucose regulation protocols may improve
      patient safety, efficiency, and nurse compliance. Such computerized clinical
      decision support systems (Cuss) use more complex logic to provide an insulin
      infusion rate based on previous blood glucose levels and other parameters. A
      computerized CDSS for glucose control has the potential to reduce overall
      workload, reduce the chance of human cognitive failure, and improve glucose
      control. Several computer-assisted glucose regulation programs have been
      published recently. In order of increasing complexity, the three main types of
      algorithms used are computerized flowcharts, Proportional-Integral-Derivative
      (PID), and Model Predictive Control (MPC). PID is essentially a closed-loop
      feedback system, whereas MPC models the behavior of glucose and insulin in ICU
      patients. Although the best approach has not yet been determined, it should be
      noted that PID controllers are generally thought to be more robust than MPC
      systems. The computerized Cuss that are most likely to emerge are those that are
      fully a part of the routine workflow, use patient-specific characteristics and
      apply variable sampling intervals.

PMID- 19849828
TI  - Fear of hypoglycaemia: defining a minimum clinically important difference in
      patients with type 2 diabetes.
AB  - BACKGROUND: To explore the concept of the Minimum Clinically Important Difference
      (MID) of the Worry Scale of the Hypoglycaemia Fear Survey (HFS-II) and to
      quantify the clinical importance of different types of patient-reported
      hypoglycaemia. METHODS: An observational study was conducted in Germany with 392
      patients with type 2 diabetes mellitus treated with combinations of oral anti
      hyperglycaemic agents. Patients completed the HFS-II, the Treatment Satisfaction
      Questionnaire for Medication (TSQM), and reported on severity of hypoglycaemia.
      Distribution- and anchor-based methods were used to determine MID. In turn, MID
      was used to determine if hypoglycaemia with or without need for assistance was
      clinically meaningful compared to having had no hypoglycaemia. RESULTS: 112
      patients (28.6%) reported hypoglycaemic episodes, with 15 patients (3.8%)
      reporting episodes that required assistance from others. Distribution- and anchor
      based methods resulted in MID between 2.0 and 5.8 and 3.6 and 3.9 for the HFS-II,
      respectively. Patients who reported hypoglycaemia with (21.6) and without (12.1)
      need for assistance scored higher on the HFS-II (range 0 to 72) than patients who
      did not report hypoglycaemia (6.0). CONCLUSION: We provide MID for HFS-II. Our
      findings indicate that the differences between having reported no hypoglycaemia,
      hypoglycaemia without need for assistance, and hypoglycaemia with need for
      assistance appear to be clinically important in patients with type 2 diabetes
      mellitus treated with oral anti-hyperglycaemic agents.

PMID- 19849829
TI  - Identification and analysis of serpin-family genes by homology and synteny across
      the 12 sequenced Drosophilid genomes.
AB  - BACKGROUND: The Drosophila melanogaster genome contains 29 serpin genes, 12 as
      single transcripts and 17 within 6 gene clusters. Many of these serpins have a
      conserved "hinge" motif characteristic of active proteinase inhibitors. However,
      a substantial proportion (42%) lacks this motif and represents non-inhibitory
      serpin-fold proteins of unknown function. Currently, it is not known whether
      orthologous, inhibitory serpin genes retain the same target proteinase
      specificity within the Drosophilid lineage, nor whether they give rise to non
      inhibitory serpin-fold proteins or other, more diverged, proteins. RESULTS: We
      collated 188 orthologues to the D. melanogaster serpins from the other 11
      Drosophilid genomes and used synteny to find further family members, raising the
      total to 226, or 71% of the number of orthologues expected assuming complete
      conservation across all 12 Drosophilid species. In general the sequence
      constraints on the serpin-fold itself are loose. The critical Reactive Centre
      Loop (RCL) sequence, including the target proteinase cleavage site, is strongly
      conserved in inhibitory serpins, although there are 3 exceptional sets of
      orthologues in which the evolutionary constraints are looser. Conversely, the RCL
      of non-inhibitory serpin orthologues is less conserved, with 3 exceptions that
      presumably bind to conserved partner molecules. We derive a consensus hinge
      motif, for Drosophilid inhibitory serpins, which differs somewhat from that of
      the vertebrate consensus. Three gene clusters appear to have originated in the
      melanogaster subgroup, Spn28D, Spn77B and Spn88E, each containing one inhibitory
      serpin orthologue that is present in all Drosophilids. In addition, the Spn100A
      transcript appears to represent a novel serpin-derived fold. CONCLUSION: In
      general, inhibitory serpins rarely change their range of proteinase targets,
      except by a duplication/divergence mechanism. Non-inhibitory serpins appear to
      derive from inhibitory serpins, but not the reverse. The conservation of
      different family members varied widely across the 12 sequenced Drosophilid
      genomes. An approach considering synteny as well as homology was important to
      find the largest set of orthologues.

PMID- 19849830
TI  - Reduction of nitrogen compounds in oceanic basement and its implications for HCN
      formation and abiotic organic synthesis.
AB  - Hydrogen cyanide is an excellent organic reagent and is central to most of the
      reaction pathways leading to abiotic formation of simple organic compounds
      containing nitrogen, such as amino acids, purines and pyrimidines. Reduced carbon
      and nitrogen precursor compounds for the synthesis of HCN may be formed under off
      axis hydrothermal conditions in oceanic lithosphere in the presence of native Fe
      and Ni and are adsorbed on authigenic layer silicates and zeolites. The native
      metals as well as the molecular hydrogen reducing CO2 to CO/CH4 and NO3-/NO2- to
      NH3/NH4+ are a result of serpentinization of mafic rocks. Oceanic plates are
      conveyor belts of reduced carbon and nitrogen compounds from the off-axis
      hydrothermal environments to the subduction zones, where compaction, dehydration,
      desiccation and diagenetic reactions affect the organic precursors. CO/CH4 and
      NH3/NH4+ in fluids distilled out of layer silicates and zeolites in the
      subducting plate at an early stage of subduction will react upon heating and form
      HCN, which is then available for further organic reactions to, for instance,
      carbohydrates, nucleosides or even nucleotides, under alkaline conditions in
      hydrated mantle rocks of the overriding plate. Convergent margins in the initial
      phase of subduction must, therefore, be considered the most potent sites for
      prebiotic reactions on Earth. This means that origin of life processes are,
      perhaps, only possible on planets where some kind of plate tectonics occur.

PMID- 19849831
TI  - Contracting private sector providers for public sector health services in
      Jalisco, Mexico: perspectives of system actors.
AB  - INTRODUCTION: Contracting out health services is a strategy that many health
      systems in the developing world are following, despite the lack of decisive
      evidence that this is the best way to improve quality, increase efficiency and
      expand coverage. A large body of literature has appeared in recent years focusing
      on the results of several contracting strategies, but very few papers have
      addressed aspects of the managerial process and how this can affect results. CASE
      DESCRIPTION: This paper describes and analyses the perceptions and opinions of
      managers and workers about the benefits and challenges of the contracting model
      that has been in place for almost 10 years in the State of Jalisco, Mexico.Both
      qualitative and quantitative information was collected. An open-ended
      questionnaire was used to obtain information from a group of managers, while
      information provided by a self-selected group of workers was collected via a
      closed-ended questionnaire. The analysis contrasted the information obtained from
      each source. DISCUSSION AND EVALUATION: Findings show that perceptions of
      managers and workers vary for most of the items studied. For managers the model
      has been a success, as it has allowed for expansion of coverage based on a cost
      effective strategy, while for workers the model also possesses positive elements
      but fails to provide fair labour relationships, which negatively affects their
      performance. CONCLUSION: Perspectives of the two main groups of actors in
      Jalisco's contracting model are important in the design and adjustment of an
      adequate contracting model that includes managerial elements to give incentives
      to worker performance, a key element necessary to achieve the model's ultimate
      objectives. Lessons learnt from this study could be relevant for the experience
      of contracting models in other developing countries.

PMID- 19849832
TI  - Evidence for the adaptation of protein pH-dependence to subcellular pH.
AB  - BACKGROUND: The availability of genome sequences, and inferred protein coding
      genes, has led to several proteome-wide studies of isoelectric points. Generally,
      isoelectric points are distributed following variations on a biomodal theme that
      originates from the predominant acid and base amino acid sidechain pKas. The
      relative populations of the peaks in such distributions may correlate with
      environment, either for a whole organism or for subcellular compartments. There
      is also a tendency for isoelectric points averaged over a subcellular location to
      not coincide with the local pH, which could be related to solubility. We now
      calculate the correlation of other pH-dependent properties, calculated from 3D
      structure, with subcellular pH. RESULTS: For proteins with known structure and
      subcellular annotation, the predicted pH at which a protein is most stable,
      averaged over a location, gives a significantly better correlation with
      subcellular pH than does isoelectric point. This observation relates to the
      cumulative properties of proteins, since maximal stability for individual
      proteins follows the bimodal isoelectric point distribution. Histidine residue
      location underlies the correlation, a conclusion that is tested against a
      background of proteins randomised with respect to this feature, and for which the
      observed correlation drops substantially. CONCLUSION: There exists a constraint
      on protein pH-dependence, in relation to the local pH, that is manifested in the
      pKa distribution of histidine sub-proteomes. This is discussed in terms of
      protein stability, pH homeostasis, and fluctuations in proton concentration.

PMID- 19849833
TI  - Using a water-immiscible ionic liquid to improve asymmetric reduction of 4
      (trimethylsilyl)-3-butyn-2-one catalyzed by immobilized Candida parapsilosis
      CCTCC M203011 cells.
AB  - BACKGROUND: Whole cells are usually employed for biocatalytic reduction reactions
      to ensure efficient coenzyme regeneration and to avoid problems with enzyme
      purification and stability. The efficiency of whole cell-catalyzed bioreduction
      is frequently restricted by pronounced toxicity of substrate and/or product to
      the microbial cells and in many instances the use of two-phase reaction systems
      can solve such problems. Therefore, we developed new, biphasic reaction systems
      with biocompatible water-immiscible ionic liquids (ILs) as alternatives to
      conventional organic solvents, in order to improve the asymmetric reduction of 4
      (trimethylsilyl)-3-butyn-2-one (TMSB) to (S)-4-(trimethylsilyl)-3-butyn-2-ol {(S)
      TMSBOL}, a key intermediate for synthesis of 5-lipoxygenase inhibitors, using
      immobilized Candida parapsilosis CCTCC M203011 cells as the biocatalyst. RESULTS:
      Various ILs exerted significant but different effects on the bioreduction. Of all
      the tested water-immiscible ILs, the best results were observed with 1-butyl-3
      methylimidazolium hexafluorophosphate (C4MIM.PF6), which exhibited not only good
      biocompatibility with the cells but also excellent solvent properties for the
      toxic substrate and product, thus markedly improving the efficiency of the
      bioreduction and the operational stability of the cells as compared to the IL
      free aqueous system. 2-Propanol was shown to be the most suitable co-substrate
      for coenzyme regeneration, and it was found that the optimum volume ratio of
      buffer to C4MIM.PF6, substrate concentration, buffer pH, 2-propanol concentration
      and reaction temperature were 4/1 (v/v), 24 mM, 5.5, 130 mM and 30 degrees C,
      respectively. Under these optimized conditions, the maximum yield and the product
      e.e. wer 97.7% and >99%, respectively, which are much higher than the
      corresponding values previously reported. The efficient whole-cell biocatalytic
      process was shown to be feasible on a 250-mL scale. CONCLUSION: The whole cell
      catalyzed asymmetric reduction of TMSB to (S)-TMSBOL can be substantially
      improved by using a C4MIM.PF6/buffer biphasic system instead of a single-phase
      aqueous system and the resulting biocatalytic process appears to be effective and
      competitive on a preparative scale.

PMID- 19849834
TI  - Inhibition of succinate dehydrogenase dysregulates histone modification in
      mammalian cells.
AB  - Remodelling of mitochondrial metabolism is a hallmark of cancer. Mutations in the
      genes encoding succinate dehydrogenase (SDH), a key Krebs cycle component, are
      associated with hereditary predisposition to pheochromocytoma and paraganglioma,
      through mechanisms which are largely unknown. Recently, the jumonji-domain
      histone demethylases have emerged as a novel family of 2-oxoglutarate-dependent
      chromatin modifiers with credible functions in tumourigenesis. Using
      pharmacological and siRNA methodologies we show that increased methylation of
      histone H3 is a general consequence of SDH loss-of-function in cultured mammalian
      cells and can be reversed by overexpression of the JMJD3 histone demethylase.
      ChIP analysis revealed that the core promoter of IGFBP7, which encodes a secreted
      protein upregulated after loss of SDHB, showed decreased occupancy by H3K27me3 in
      the absence of SDH. Finally, we provide the first evidence that the chief (type
      I) cell is the major methylated histone-immunoreactive constituent of
      paraganglioma. These results support the notion that loss of mitochondrial
      function alters epigenetic processes and might provide a signature methylation
      mark for paraganglioma.

PMID- 19849835
TI  - Comparison of embedded and added motor imagery training in patients after stroke:
      study protocol of a randomised controlled pilot trial using a mixed methods
      approach.
AB  - BACKGROUND: Two different approaches have been adopted when applying motor
      imagery (MI) to stroke patients. MI can be conducted either added to conventional
      physiotherapy or integrated within therapy sessions. The proposed study aims to
      compare the efficacy of embedded MI to an added MI intervention. Evidence from
      pilot studies reported in the literature suggests that both approaches can
      improve performance of a complex motor skill involving whole body movements,
      however, it remains to be demonstrated, which is the more effective one.
      METHODS/DESIGN: A single blinded, randomised controlled trial (RCT) with a pre
      post intervention design will be carried out. The study design includes two
      experimental groups and a control group (CG). Both experimental groups (EG1, EG2)
      will receive physical practice of a clinical relevant motor task ('Going down,
      laying on the floor, and getting up again') over a two week intervention period:
      EG1 with embedded MI training, EG2 with MI training added after physiotherapy.
      The CG will receive standard physiotherapy intervention and an additional control
      intervention not related to MI. The primary study outcome is the time difference
      to perform the task from pre to post-intervention. Secondary outcomes include
      level of help needed, stages of motor task completion, degree of motor
      impairment, balance ability, fear of falling measure, motivation score, and motor
      imagery ability score. Four data collection points are proposed: twice during
      baseline phase, once following the intervention period, and once after a two week
      follow up. A nested qualitative part should add an important insight into
      patients' experience and attitudes towards MI. Semi-structured interviews of six
      to ten patients, who participate in the RCT, will be conducted to investigate
      patients' previous experience with MI and their expectations towards the MI
      intervention in the study. Patients will be interviewed prior and after the
      intervention period. DISCUSSION: Results will determine whether embedded MI is
      superior to added MI. Findings of the semi-structured interviews will help to
      integrate patient's expectations of MI interventions in the design of research
      studies to improve practical applicability using MI as an adjunct therapy
      technique.

PMID- 19849837
TI  - Web GIS in practice VII: stereoscopic 3-D solutions for online maps and virtual
      globes.
AB  - Because our pupils are about 6.5 cm apart, each eye views a scene from a
      different angle and sends a unique image to the visual cortex, which then merges
      the images from both eyes into a single picture. The slight difference between
      the right and left images allows the brain to properly perceive the 'third
      dimension' or depth in a scene (stereopsis). However, when a person views a
      conventional 2-D (two-dimensional) image representation of a 3-D (three
      dimensional) scene on a conventional computer screen, each eye receives
      essentially the same information. Depth in such cases can only be approximately
      inferred from visual clues in the image, such as perspective, as only one image
      is offered to both eyes. The goal of stereoscopic 3-D displays is to project a
      slightly different image into each eye to achieve a much truer and realistic
      perception of depth, of different scene planes, and of object relief. This paper
      presents a brief review of a number of stereoscopic 3-D hardware and software
      solutions for creating and displaying online maps and virtual globes (such as
      Google Earth) in "true 3D", with costs ranging from almost free to multi-thousand
      pounds sterling. A practical account is also given of the experience of the USGS
      BRD UMESC (United States Geological Survey's Biological Resources Division, Upper
      Midwest Environmental Sciences Center) in setting up a low-cost, full-colour
      stereoscopic 3-D system.

PMID- 19849836
TI  - Simultaneous transcription of duplicated var2csa gene copies in individual
      Plasmodium falciparum parasites.
AB  - BACKGROUND: Single nucleotide polymorphisms are common in duplicated genes,
      causing functional preservation, alteration or silencing. The Plasmodium
      falciparum genes var2csa and Pf332 are duplicated in the haploid genome of the
      HB3 parasite line. Whereas the molecular function of Pf332 remains to be
      elucidated, VAR2CSA is known to be the main adhesin in placental parasite
      sequestration. Sequence variations introduced upon duplication of these genes
      provide discriminative possibilities to analyze allele-specific transcription
      with a bearing towards understanding gene dosage impact on parasite biology.
      RESULTS: We demonstrate an approach combining real-time PCR allelic
      discrimination and discriminative RNA-FISH to distinguish between highly similar
      gene copies in P. falciparum parasites. The duplicated var2csa variants are
      simultaneously transcribed, both on a population level and intriguingly also in
      individual cells, with nuclear co-localization of the active genes and
      corresponding transcripts. This indicates transcriptional functionality of
      duplicated genes, challenges the dogma of mutually exclusive var gene
      transcription and suggests mechanisms behind antigenic variation, at least in
      respect to the duplicated and highly similar var2csa genes. CONCLUSIONS: Allelic
      discrimination assays have traditionally been applied to study zygosity in
      diploid genomes. The assays presented here are instead successfully applied to
      the identification and evaluation of transcriptional activity of duplicated genes
      in the haploid genome of the P. falciparum parasite. Allelic discrimination and
      gene or transcript localization by FISH not only provide insights into
      transcriptional regulation of genes such as the virulence associated var genes,
      but also suggest that this sensitive and precise approach could be used for
      further investigation of genome dynamics and gene regulation.

PMID- 19849838
TI  - Authentication scheme for routine verification of genetically similar laboratory
      colonies: a trial with Anopheles gambiae.
AB  - BACKGROUND: When rearing morphologically indistinguishable laboratory strains
      concurrently, the threat of unintentional genetic contamination is constant.
      Avoidance of accidental mixing of strains is difficult due to the use of common
      equipment, technician error, or the possibility of self relocation by adult
      mosquitoes ("free fliers"). In many cases, laboratory strains are difficult to
      distinguish because of morphological and genetic similarity, especially when
      laboratory colonies are isolates of certain traits from the same parental strain,
      such as eye color mutants, individuals with certain chromosomal arrangements or
      high levels of insecticide resistance. Thus, proving genetic integrity could seem
      incredibly time-consuming or impossible. On the other hand, lacking proof of
      genetically isolated laboratory strains could question the validity of research
      results. RESULTS: We present a method for establishing authentication matrices to
      routinely distinguish and confirm that laboratory strains have not become
      physically or genetically mixed through contamination events in the laboratory.
      We show a specific example with application to Anopheles gambiae sensu stricto
      strains at the Malaria Research and Reference Reagent Resource Center. This
      authentication matrix is essentially a series of tests yielding a strain-specific
      combination of results. CONCLUSION: These matrix-based methodologies are useful
      for several mosquito and insect populations but must be specifically tailored and
      altered for each laboratory based on the potential contaminants available at any
      given time. The desired resulting authentication plan would utilize the least
      amount of routine effort possible while ensuring the integrity of the strains.

PMID- 19849839
TI  - Grammatical-Restrained Hidden Conditional Random Fields for Bioinformatics
      applications.
AB  - BACKGROUND: Discriminative models are designed to naturally address
      classification tasks. However, some applications require the inclusion of grammar
      rules, and in these cases generative models, such as Hidden Markov Models (HMMs)
      and Stochastic Grammars, are routinely applied. RESULTS: We introduce Grammatical
      Restrained Hidden Conditional Random Fields (GRHCRFs) as an extension of Hidden
      Conditional Random Fields (HCRFs). GRHCRFs while preserving the discriminative
      character of HCRFs, can assign labels in agreement with the production rules of a
      defined grammar. The main GRHCRF novelty is the possibility of including in HCRFs
      prior knowledge of the problem by means of a defined grammar. Our current
      implementation allows regular grammar rules. We test our GRHCRF on a typical
      biosequence labeling problem: the prediction of the topology of Prokaryotic outer
      membrane proteins. CONCLUSION: We show that in a typical biosequence labeling
      problem the GRHCRF performs better than CRF models of the same complexity,
      indicating that GRHCRFs can be useful tools for biosequence analysis
      applications. AVAILABILITY: GRHCRF software is available under GPLv3 licence at
      the websitehttp://www.biocomp.unibo.it/~savojard/biocrf-0.9.tar.gz.

PMID- 19849840
TI  - The nuclear envelopathies and human diseases.
AB  - The nuclear envelope (NE) consists of two membrane layers that segregate the
      nuclear from the cytoplasmic contents. Recent progress in our understanding of
      nuclear-lamina associated diseases has revealed intriguing connections between
      the envelope components and nuclear processes. Here, we review the functions of
      the nuclear envelope in chromosome organization, gene expression, DNA repair and
      cell cycle progression, and correlate deficiencies in envelope function with
      human pathologies.

PMID- 19849841
TI  - Smad4-dependent pathways control basement membrane deposition and endodermal cell
      migration at early stages of mouse development.
AB  - BACKGROUND: Smad4 mutant embryos arrest shortly after implantation and display a
      characteristic shortened proximodistal axis, a significantly reduced epiblast, as
      well as a thickened visceral endoderm layer. Conditional rescue experiments
      demonstrate that bypassing the primary requirement for Smad4 in the extra
      embryonic endoderm allows the epiblast to gastrulate. Smad4-independent TGF-beta
      signals are thus sufficient to promote mesoderm formation and patterning. To
      further analyse essential Smad4 activities contributed by the extra-embryonic
      tissues, and characterise Smad4 dependent pathways in the early embryo, here we
      performed transcriptional profiling of Smad4 null embryonic stem (ES) cells and
      day 4 embryoid bodies (EBs). RESULTS: Transcripts from wild-type versus Smad4
      null ES cells and day 4 EBs were analysed using Illumina arrays. In addition to
      several known TGF-beta/BMP target genes, we identified numerous Smad4-dependent
      transcripts that are mis-expressed in the mutants. As expected, mesodermal cell
      markers were dramatically down-regulated. We also observed an increase in non
      canonical potency markers (Pramel7, Tbx3, Zscan4), germ cell markers (Aire,
      Tuba3a, Dnmt3l) as well as early endoderm markers (Dpp4, H19, Dcn). Additionally,
      expression of the extracellular matrix (ECM) remodelling enzymes Mmp14 and Mmp9
      was decreased in Smad4 mutant ES and EB populations. These changes, in
      combination with increased levels of laminin alpha1, cause excessive basement
      membrane deposition. Similarly, in the context of the Smad4 null E6.5 embryos we
      observed an expanded basement membrane (BM) associated with the thickened
      endoderm layer. CONCLUSION: Smad4 functional loss results in a dramatic shift in
      gene expression patterns and in the endodermal cell lineage causes an excess
      deposition of, or an inability to breakdown and remodel, the underlying BM layer.
      These structural abnormalities probably disrupt reciprocal signalling between the
      epiblast and overlying visceral endoderm required for gastrulation.

PMID- 19849842
TI  - Acute sensorineural hearing loss and severe otalgia due to scrub typhus.
AB  - BACKGROUND: Scrub typhus is an acute febrile illness caused by Orientia
      tsutsugamushi. CASE PRESENTATIONS: We encountered a patient with sensorineural
      hearing loss complicating scrub typhus, and three patients with scrub typhus who
      complained of otalgia, which was sudden onset, severe, paroxysmal, intermittent
      yet persistent pain lasting for several seconds, appeared within 1 week after the
      onset of fever and rash. The acute sensorineural hearing loss and otalgia were
      resolved after antibiotic administration. CONCLUSION: When patients in endemic
      areas present with fever and rash and have sensorineural hearing loss or otalgia
      without otoscopic abnormalities, clinicians should suspect scrub typhus and
      consider empirical antibiotic therapy.

PMID- 19849843
TI  - Hsp-90 and the biology of nematodes.
AB  - BACKGROUND: Hsp-90 from the free-living nematode Caenorhabditis elegans is unique
      in that it fails to bind to the specific Hsp-90 inhibitor, geldanamycin (GA).
      Here we surveyed 24 different free-living or parasitic nematodes with the aim of
      determining whether C. elegans Hsp-90 was the exception or the norm amongst the
      nematodes. We combined these data with codon evolution models in an attempt to
      identify whether hsp-90 from GA-binding and non-binding species has evolved under
      different evolutionary constraints. RESULTS: We show that GA-binding is
      associated with life history: free-living nematodes and those parasitic species
      with free-living larval stages failed to bind GA. In contrast, obligate parasites
      and those worms in which the free-living stage in the environment is enclosed
      within a resistant egg, possess a GA-binding Hsp-90. We analysed Hsp-90 sequences
      from fifteen nematode species to determine whether nematode hsp-90s have
      undergone adaptive evolution that influences GA-binding. Our data provide
      evidence of rapid diversifying selection in the evolution of the hsp-90 gene
      along three separate lineages, and identified a number of residues showing
      significant evidence of adaptive evolution. However, we were unable to prove that
      the selection observed is correlated with the ability to bind geldanamycin or
      not. CONCLUSION: Hsp-90 is a multi-functional protein and the rapid evolution of
      the hsp-90 gene presumably correlates with other key cellular functions. Factors
      other than primary amino acid sequence may influence the ability of Hsp-90 to
      bind to geldanamycin.

PMID- 19849844
TI  - Clinical meaning of age-related expression of fecal cytokeratin 19 in colorectal
      malignancy.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of malignant
      death worldwide. Because young age of onset is often considered a poor prognostic
      factor for CRC, it is important to identify the poor outcomes of CRC in a younger
      population and to consider an aggressive approach by implementing early
      treatment. Our aim was to specifically quantify the fecal cytokeratin 19 (CK19)
      transcript from CRC patients and investigate its correlation with clinical stage,
      tumor malignancy, and age. METHODS: The quantitation of fecal CK19 transcript was
      determined by a quantitative real-time reverse transcription polymerase chain in
      129 CRC patients (45 younger than 60 years at diagnosis) and 85 healthy controls.
      The levels of CK19 protein were examined both in colonic cell lines and tissues.
      RESULTS: The analysis of 45 younger CRC patients (age <or= 60 years) revealed
      that patients at the M1 stage had significantly higher expression levels of fecal
      CK19 mRNA when compared with healthy controls (p < 0.001) and patients at the M0
      stage (p = 0.004). Additionally, the degree of consistency between the mean level
      of fecal CK19 mRNA and the distant metastatic rate in each age interval was up to
      89% (p = 0.042). CONCLUSION: These results indicate that high levels of fecal
      CK19 mRNA represent a potential marker for colorectal malignancy and for
      aggressive treatment of younger CRC patients.

PMID- 19849846
TI  - Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory
      phenotypes without any regulatory/suppressor function.
AB  - BACKGROUND: Foxp3 has been suggested to be a standard marker for murine Tregs
      whereas its role as marker for human Tregs is controversial. While some reports
      have shown that human Foxp3+ T cells had no regulatory function others have shown
      their role in the inhibition of T cell proliferation. METHODS: T cell activation
      was performed by means of brayostatin-1/ionomycin (B/I), mixed lymphocyte
      reaction (MLR), and CD3/CD28 activation. T cell proliferation was performed using
      BrdU and CFSE staining. Flow cytometry was performed to determine Foxp3
      expression, cell proliferation, viabilities and phenotype analyses of T cells.
      RESULTS: Both CD4+ and CD8+ T cells expressed Foxp3 upon activation in vitro.
      Expression of Foxp3 remained more stable in CD4+CD25+ T cells compared to that in
      CD8+CD25+ T cells. The CD4+CD25+Foxp3+ T cells expressed CD44 and CD62L, showing
      their effector and memory phenotypes. Both FoxP3- responder T cells and
      CD4+FoxP3+ T cells underwent proliferation upon CD3/CD28 activation. CONCLUSION:
      Expression of Foxp3 does not necessarily convey regulatory function in human
      CD4+CD25+ T cells. Increased FoxP3 on CD44+ effector and CD44+CD62L+ memory T
      cells upon stimulation suggest the activation-induced regulation of FoxP3
      expression.

PMID- 19849845
TI  - Estrogen treatment following severe burn injury reduces brain inflammation and
      apoptotic signaling.
AB  - BACKGROUND: Patients with severe burn injury experience a rapid elevation in
      multiple circulating pro-inflammatory cytokines, with the levels correlating with
      both injury severity and outcome. Accumulations of these cytokines in animal
      models have been observed in remote organs, however data are lacking regarding
      early brain cytokine levels following burn injury, and the effects of estradiol
      on these levels. Using an experimental animal model, we studied the acute effects
      of a full-thickness third degree burn on brain levels of TNF-alpha, IL-1beta, and
      IL-6 and the protective effects of acute estrogen treatment on these levels.
      Additionally, the acute administration of estrogen on regulation of inflammatory
      and apoptotic events in the brain following severe burn injury were studied
      through measuring the levels of phospho-ERK, phospho-Akt, active caspase-3, and
      PARP cleavage in the placebo and estrogen treated groups. METHODS: In this study,
      149 adult Sprague-Dawley male rats received 3rd degree 40% total body surface
      area (TBSA) burns. Fifteen minutes following burn injury, the animals received a
      subcutaneous injection of either placebo (n = 72) or 17 beta-estradiol (n = 72).
      Brains were harvested at 0.5, 1, 2, 4, 6, 8, 12, 18, and 24 hours after injury
      from the control (n = 5), placebo (n = 8/time point), and estrogen treated
      animals (n = 8/time point). The brain cytokine levels were measured using the
      ELISA method. In addition, we assessed the levels of phosphorylated-ERK,
      phosphorylated-Akt, active caspase-3, and the levels of cleaved PARP at the 24
      hour time-point using Western blot analysis. RESULTS: In burned rats, 17 beta
      estradiol significantly decreased the levels of brain tissue TNF-alpha
      (approximately 25%), IL-1beta (approximately 60%), and IL-6 (approximately 90%)
      when compared to the placebo group. In addition, we determined that in the
      estrogen-treated rats there was an increase in the levels of phospho-ERK (p <
      0.01) and Akt (p < 0.05) at the 24 hour time-point, and that 17 beta-estradiol
      blocked the activation of caspase-3 (p < 0.01) and subsequent cleavage of PARP (p
      < 0.05). CONCLUSION: Following severe burn injury, estrogens decrease both brain
      inflammation and the activation of apoptosis, represented by an increase in the
      levels of phospho-Akt and inhibition of caspase-3 activation and PARP cleavage.
      Results from these studies will help further our understanding of how estrogens
      protect the brain following burn injury, and may provide a novel, safe, and
      effective clinical treatment to combat remote secondary burn injury in the brain
      and to preserve cognition.

PMID- 19849847
TI  - Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines
      is associated with epithelial-mesenchymal transition (EMT).
AB  - BACKGROUND: The glycosylphosphatidylinositol (GPI)-anchored epithelial
      extracellular membrane serine protease prostasin (PRSS8) is expressed abundantly
      in normal epithelia and essential for terminal epithelial differentiation, but
      down-regulated in human prostate, breast, and gastric cancers and invasive cancer
      cell lines. Prostasin is involved in the extracellular proteolytic modulation of
      the epidermal growth factor receptor (EGFR) and is an invasion suppressor. The
      aim of this study was to evaluate prostasin expression states in the transitional
      cell carcinomas (TCC) of the human bladder and in human TCC cell lines. METHODS:
      Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA)
      were evaluated for prostasin expression by means of immunohistochemistry. A panel
      of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin
      expression by western blot and quantitative PCR, and for prostasin gene promoter
      region CpG methylation by methylation-specific PCR (MSP). RESULTS: Prostasin is
      expressed in the normal human urothelium and in a normal human urothelial cell
      line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15)
      TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated
      with loss of or reduced E-cadherin expression, loss of epithelial morphology, and
      promoter DNA hypermethylation. Prostasin expression could be reactivated by
      demethylation or inhibition of histone deacetylase. Re-expression of prostasin or
      a serine protease-inactive variant resulted in transcriptional up-regulation of E
      cadherin. CONCLUSION: Loss of prostasin expression in bladder transitional cell
      carcinomas is associated with epithelial-mesenchymal transition (EMT), and may
      have functional implications in tumor invasion and resistance to chemotherapy.

PMID- 19849848
TI  - Simple modeling of FtsZ polymers on flat and curved surfaces: correlation with
      experimental in vitro observations.
AB  - FtsZ is a GTPase that assembles at midcell into a dynamic ring that constricts
      the membrane to induce cell division in the majority of bacteria, in many archea
      and several organelles. In vitro, FtsZ polymerizes in a GTP-dependent manner
      forming a variety of filamentous flexible structures. Based on data derived from
      the measurement of the in vitro polymerization of Escherichia coli FtsZ cell
      division protein we have formulated a model in which the fine balance between
      curvature, flexibility and lateral interactions accounts for structural and
      dynamic properties of the FtsZ polymers observed with AFM. The experimental
      results have been used by the model to calibrate the interaction energies and the
      values obtained indicate that the filaments are very plastic. The extension of
      the model to explore filament behavior on a cylindrical surface has shown that
      the FtsZ condensates promoted by lateral interactions can easily form ring
      structures through minor modulations of either filament curvature or longitudinal
      bond energies. The condensation of short, monomer exchanging filaments into rings
      is shown to produce enough force to induce membrane deformations.PACS codes:
      87.15.ak, 87.16.ka, 87.17.Ee.

PMID- 19849849
TI  - CD74 interacts with APP and suppresses the production of Abeta.
AB  - BACKGROUND: Alzheimer disease (AD) is characterized by senile plaques, which are
      mainly composed of beta amyloid (Abeta) peptides. Abeta is cleaved off from
      amyloid precursor protein (APP) with consecutive proteolytic processing by beta
      secretase and gamma-secretase. RESULTS: Here, we show that CD74, the invariant
      chain of class II major histocompatibility complex, interacts with APP and serves
      as a negative regulator of Abeta. CD74 resembles other APP interacters such as
      BRI2 and BRI3, since all of them reduce the level of Abeta. However, unlike BRIs,
      CD74 does not reduce the secretion of sAPPalpha or sAPPbeta. Interestingly, in
      HeLa cells, over expression of CD74 steers APP, but not Notch, to large vacuoles
      created by CD74. CONCLUSION: Taken together, we propose that CD74 inhibits Abeta
      production by interacting with and derailing normal trafficking of APP.

PMID- 19849850
TI  - Whole-genome resequencing of Escherichia coli K-12 MG1655 undergoing short-term
      laboratory evolution in lactate minimal media reveals flexible selection of
      adaptive mutations.
AB  - BACKGROUND: Short-term laboratory evolution of bacteria followed by genomic
      sequencing provides insight into the mechanism of adaptive evolution, such as the
      number of mutations needed for adaptation, genotype-phenotype relationships, and
      the reproducibility of adaptive outcomes. RESULTS: In the present study, we
      describe the genome sequencing of 11 endpoints of Escherichia coli that underwent
      60-day laboratory adaptive evolution under growth rate selection pressure in
      lactate minimal media. Two to eight mutations were identified per endpoint.
      Generally, each endpoint acquired mutations to different genes. The most notable
      exception was an 82 base-pair deletion in the rph-pyrE operon that appeared in 7
      of the 11 adapted strains. This mutation conferred an approximately 15% increase
      to the growth rate when experimentally introduced to the wild-type background and
      resulted in an approximately 30% increase to growth rate when introduced to a
      background already harboring two adaptive mutations. Additionally, most endpoints
      had a mutation in a regulatory gene (crp or relA, for example) or the RNA
      polymerase. CONCLUSIONS: The 82 base-pair deletion found in the rph-pyrE operon
      of many endpoints may function to relieve a pyrimidine biosynthesis defect
      present in MG1655. In contrast, a variety of regulators acquire mutations in the
      different endpoints, suggesting flexibility in overcoming regulatory challenges
      in the adaptation.

PMID- 19849851
TI  - Enhancing innovation between scientific and indigenous knowledge: pioneer NGOs in
      India.
AB  - BACKGROUND: Until recently, little attention has been paid to local innovation
      capacity as well as management practices and institutions developed by
      communities and other local actors based on their traditional knowledge. This
      paper doesn't focus on the results of scientific research into innovation
      systems, but rather on how local communities, in a network of supportive
      partnerships, draw knowledge for others, combine it with their own knowledge and
      then innovate in their local practices. Innovation, as discussed in this article,
      is the capacity of local stakeholders to play an active role in innovative
      knowledge creation in order to enhance local health practices and further
      environmental conservation. In this article, the innovative processes through
      which this capacity is created and reinforced will be defined as a process of
      "ethnomedicine capacity". METHODS: The field study undertaken by the first author
      took place in India, in the State of Tamil Nadu, over a period of four months in
      2007. The data was collected through individual interviews and focus groups and
      was complemented by participant observations. RESULTS: The research highlights
      the innovation capacity related to ethnomedical knowledge. As seen, the
      integration of local and scientific knowledge is crucial to ensure the practices
      anchor themselves in daily practices. The networks created are clearly
      instrumental to enhancing the innovation capacity that allows the creation,
      dissemination and utilization of 'traditional' knowledge. However, these networks
      have evolved in very different forms and have become entities that can fit into
      global networks. The ways in which the social capital is enhanced at the village
      and network levels are thus important to understand how traditional knowledge can
      be used as an instrument for development and innovation. CONCLUSION: The case
      study analyzed highlights examples of innovation systems in a developmental
      context. They demonstrate that networks comprised of several actors from
      different levels can synergistically forge linkages between local knowledge and
      formal sciences and generate positive and negative impacts. The positive impact
      is the revitalization of perceived traditions while the negative impacts pertain
      to the transformation of these traditions into health commodities controlled by
      new elites, due to unequal power relations.

PMID- 19849852
TI  - Ginseng leaf-stem: bioactive constituents and pharmacological functions.
AB  - Ginseng root is used more often than other parts such as leaf stem although
      extracts from ginseng leaf-stem also contain similar active ingredients with
      pharmacological functions. Ginseng's leaf-stems are more readily available at a
      lower cost than its root. This article reviews the pharmacological effects of
      ginseng leaf-stem on some diseases and adverse effects due to excessive
      consumption. Ginseng leaf-stem extract contains numerous active ingredients, such
      as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils,
      polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract
      contains larger amounts of the same active ingredients than the root. These
      active ingredients produce multifaceted pharmacological effects on the central
      nervous system, as well as on the cardiovascular, reproductive and metabolic
      systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic,
      anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use,
      ginseng leaf-stem extract is quite safe; adverse effects occur only when it is
      over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have
      similar multifaceted pharmacological activities (for example central nervous and
      cardiovascular systems). In terms of costs and source availability, however,
      ginseng leaf-stem has advantages over its root. Further research will facilitate
      a wider use of ginseng leaf-stem.

PMID- 19849853
TI  - Pathophysiology of cell phone radiation: oxidative stress and carcinogenesis with
      focus on male reproductive system.
AB  - Hazardous health effects stemming from exposure to radiofrequency electromagnetic
      waves (RF-EMW) emitted from cell phones have been reported in the literature.
      However, the cellular target of RF-EMW is still controversial. This review
      identifies the plasma membrane as a target of RF-EMW. In addition, the effects of
      RF-EMW on plasma membrane structures (i.e. NADH oxidase, phosphatidylserine,
      ornithine decarboxylase) and voltage-gated calcium channels are discussed. We
      explore the disturbance in reactive oxygen species (ROS) metabolism caused by RF
      EMW and delineate NADH oxidase mediated ROS formation as playing a central role
      in oxidative stress (OS) due to cell phone radiation (with a focus on the male
      reproductive system). This review also addresses: 1) the controversial effects of
      RF-EMW on mammalian cells and sperm DNA as well as its effect on apoptosis, 2)
      epidemiological, in vivo animal and in vitro studies on the effect of RF-EMW on
      male reproductive system, and 3) finally, exposure assessment and dosimetry by
      computational biomodeling.

PMID- 19849854
TI  - Does evolutionary innovation in pharyngeal jaws lead to rapid lineage
      diversification in labrid fishes?
AB  - BACKGROUND: Major modifications to the pharyngeal jaw apparatus are widely
      regarded as a recurring evolutionary key innovation that has enabled adaptive
      radiation in many species-rich clades of percomorph fishes. However one of the
      central predictions of this hypothesis, that the acquisition of a modified
      pharyngeal jaw apparatus will be positively correlated with explosive lineage
      diversification, has never been tested. We applied comparative methods to a new
      time-calibrated phylogeny of labrid fishes to test whether diversification rates
      shifted at two scales where major pharyngeal jaw innovations have evolved: across
      all of Labridae and within the subclade of parrotfishes. RESULTS: Diversification
      patterns within early labrids did not reflect rapid initial radiation. Much of
      modern labrid diversity stems from two recent rapid diversification events; one
      within julidine fishes and the other with the origin of the most species-rich
      clade of reef-associated parrotfishes. A secondary pharyngeal jaw innovation was
      correlated with rapid diversification within the parrotfishes. However
      diversification rate shifts within parrotfishes are more strongly correlated with
      the evolution of extreme dichromatism than with pharyngeal jaw modifications.
      CONCLUSION: The temporal lag between pharyngeal jaw modifications and changes in
      diversification rates casts doubt on the key innovation hypothesis as a simple
      explanation for much of the richness seen in labrids and scarines. Although the
      possession of a secondarily modified PJA was correlated with increased
      diversification rates, this pattern is better explained by the evolution of
      extreme dichromatism (and other social and behavioral characters relating to
      sexual selection) within Scarus and Chlorurus. The PJA-innovation hypothesis also
      fails to explain the most dominant aspect of labrid lineage diversification, the
      radiation of the julidines. We suggest that pharyngeal jaws might have played a
      more important role in enabling morphological evolution of the feeding apparatus
      in labrids and scarines rather than in accelerating lineage diversification.

PMID- 19849855
TI  - Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular
      carcinoma cells.
AB  - BACKGROUND: beta-catenin mutations that constitutively activate the canonical Wnt
      signaling have been observed in a subset of hepatocellular carcinomas (HCCs).
      These mutations are associated with chromosomal stability, low histological
      grade, low tumor invasion and better patient survival. We hypothesized that
      canonical Wnt signaling is selectively activated in well-differentiated, but
      repressed in poorly differentiated HCCs. To this aim, we characterized
      differentiation status of HCC cell lines and compared their expression status of
      Wnt pathway genes, and explored their activity of canonical Wnt signaling.
      RESULTS: We classified human HCC cell lines into "well-differentiated" and
      "poorly differentiated" subtypes, based on the expression of hepatocyte lineage,
      epithelial and mesenchymal markers. Poorly differentiated cell lines lost
      epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers.
      Also, they were highly motile and invasive. We compared the expression of 45 Wnt
      pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co
      receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and
      canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical
      ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed
      selectively in well- and poorly differentiated cell lines, respectively.
      Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected
      in 80% of well-differentiated, contrary to 14% of poorly differentiated cell
      lines. TCF activity generated by ectopic mutant beta-catenin was weak in poorly
      differentiated SNU449 cell line, suggesting a repressive mechanism. We tested
      Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling
      that is activated by mutant beta-catenin in HCC cell lines. CONCLUSION:
      Differential expression of Wnt ligands in HCC cells is associated with selective
      activation of canonical Wnt signaling in well-differentiated, and its repression
      in poorly differentiated cell lines. One potential mechanism of repression
      involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our
      observations support the hypothesis that Wnt pathway is selectively activated or
      repressed depending on differentiation status of HCC cells. We propose that
      canonical and noncanonical Wnt pathways have complementary roles in HCC, where
      the canonical signaling contributes to tumor initiation, and noncanonical
      signaling to tumor progression.

PMID- 19849856
TI  - Leptin interferes with 3',5'-cyclic adenosine monophosphate (cAMP) signaling to
      inhibit steroidogenesis in human granulosa cells.
AB  - BACKGROUND: Obesity has been linked to an increased risk of female infertility.
      Leptin, an adipocytokine which is elevated during obesity, may influence gonadal
      function through modulating steroidogenesis in granulosa cells. METHODS: The
      effect of leptin on progesterone production in simian virus 40 immortalized
      granulosa (SVOG) cells was examined by Enzyme linked immunosorbent assay (ELISA).
      The effect of leptin on the expression of the steroidogenic enzymes (StAR,
      P450scc, 3betaHSD) in SVOG cells was examined by real-time PCR and Western
      blotting. The mRNA expression of leptin receptor isoforms in SVOG cells were
      examined by using PCR. SVOG cells were co-treated with leptin and specific
      pharmacological inhibitors to identify the signaling pathways involved in leptin
      reduced progesterone production. Silencing RNA against leptin receptor was used
      to determine that the inhibition of leptin on cAMP-induced steroidogenesis acts
      in a leptin receptor-dependent manner. RESULTS AND CONCLUSION: In the present
      study, we investigated the cellular mechanisms underlying leptin-regulated
      steroidogenesis in human granulosa cells. We show that leptin inhibits 8-bromo
      cAMP-stimulated progesterone production in a concentration-dependent manner.
      Furthermore, we show that leptin inhibits expression of the cAMP-stimulated
      steroidogenic acute regulatory (StAR) protein, the rate limiting de novo protein
      in progesterone synthesis. Leptin induces the activation of ERK1/2, p38 and JNK
      but only the ERK1/2 (PD98059) and p38 (SB203580) inhibitors attenuate the leptin
      induced inhibition of cAMP-stimulated StAR protein expression and progesterone
      production. These data suggest that the leptin-induced MAPK signal transduction
      pathway interferes with cAMP/PKA-stimulated steroidogenesis in human granulosa
      cells. Moreover, siRNA mediated knock-down of the endogenous leptin receptor
      attenuates the effect of leptin on cAMP-induced StAR protein expression and
      progesterone production, suggesting that the effect of leptin on steroidogenesis
      in granulosa cells is receptor dependent. In summary, leptin acts through the
      MAPK pathway to downregulate cAMP-induced StAR protein expression and
      progesterone production in immortalized human granulosa cells. These results
      suggest a possible mechanism by which gonadal steroidogenesis could be suppressed
      in obese women.

PMID- 19849857
TI  - A cluster-randomized controlled trial evaluating the effect of culturally
      appropriate hypertension education among Afro-Surinamese and Ghanaian patients in
      Dutch general practice: study protocol.
AB  - BACKGROUND: Individuals of African descent living in western countries have
      increased rates of hypertension and hypertension-related complications. Poor
      adherence to hypertension treatment (medication and lifestyle changes) has been
      identified as one of the most important modifiable causes for the observed
      disparities in hypertension related complications, with patient education being
      recommended to improve adherence. Despite evidence that culturally-appropriate
      patient education may improve the overall quality of care for ethnic minority
      patients, few studies have focused on how hypertensive individuals of African
      descent respond to this approach. This paper describes the design of a study that
      compares the effectiveness of culturally-appropriate hypertension education with
      that of the standard approach among Surinamese and Ghanaian hypertensive patients
      with an elevated blood pressure in Dutch primary care practices. METHODS/DESIGN:
      A cluster-randomized controlled trial will be conducted in four primary care
      practices in Amsterdam, all offering hypertension care according to Dutch
      clinical guidelines. After randomization, patients in the usual care sites (n =
      2) will receive standard hypertension education. Patients in the intervention
      sites (n = 2) will receive three culturally-appropriate hypertension education
      sessions, culturally-specific educational materials and targeted lifestyle
      support. The primary outcome will be the proportion of patients with a reduction
      in systolic blood pressure >or= 10 mmHg at eight months after the start of the
      trial. The secondary outcomes will be the proportion of patients with self
      reported adherence to (i) medication and (ii) lifestyle recommendations at eight
      months after the start of the trial. The study will enrol 148 patients (74 per
      condition, 37 per site). Eligibility criteria for patients of either sex will be:
      current diagnosis of hypertension, self-identified Afro-Surinamese or Ghanaian,
      >or= 20 years, and baseline blood pressure >or= 140/90 mmHg. Primary and
      secondary outcomes will be measured at baseline and at 3 1/2, 6 1/2, and eight
      months. Other measurements will be performed at baseline and eight months.
      DISCUSSION: The findings will provide new knowledge on how to improve blood
      pressure control and patient adherence in ethnic minority persons with a high
      risk of negative hypertension-related health outcomes. TRIAL REGISTRATION:
      ISRCTN35675524.

PMID- 19849859
TI  - Biomechanical analysis of the relation between movement time and joint moment
      development during a sit-to-stand task.
AB  - BACKGROUND: Slowness of movement is a factor that may cause a decrease of quality
      of daily life. Mobility in the elderly and people with movement impairments may
      be improved by increasing the quickness of fundamental locomotor tasks. Because
      it has not been revealed how much muscle strength is required to improve
      quickness, the purpose of this study was to reveal the relation between movement
      time and the required muscle strength in a sit to stand (STS) task. Previous
      research found that the sum of the peak hip and knee joint moments was relatively
      invariant throughout a range of movement patterns (Yoshioka et al., 2007,
      Biomedical Engineering Online 6:26). The sum of the peak hip and knee joint
      moment is an appropriate index to evaluate the muscle strength required for an
      STS task, since the effect of the movement pattern variation can be reduced, that
      is, the results can be evaluated purely from the viewpoint of the movement times.
      Therefore, the sum of the peak hip and knee joint moment was used as the index to
      indicate the required muscle strength. METHODS: Experimental kinematics data were
      collected from 11 subjects. The time at which the vertical position of the right
      shoulder fell outside three standard deviations of the vertical positions during
      the static initial posture was regarded as the start time. The time at which the
      vertical position fell within three standard deviations of the vertical positions
      during static upright standing posture was regarded as the finish time. Each
      movement time of the experimental movements was linearly lengthened and shortened
      through post-processing. Combining the experimental procedure and the post
      processing, movements having various movement patterns and a wide range of
      movement times were obtained. The joint moment and the static and inertial
      components of the joint moment were calculated with an inverse dynamics method.
      The static component reflects the gravitational and/or external forces, while the
      inertial component reflects the acceleration of the body. RESULTS: The
      quantitative relation between the movement time and the sum of the peak hip and
      knee joint moments were obtained. As the STS movement time increased, the joint
      moments decreased exponentially and converged to the static component (1.51
      approximately 1.54 N.m/kg). When the movement time was the longest (movement
      time: 7.0 seconds), the joint moments (1.57 N.m/kg) closely corresponded to the
      minimum of 1.53 N.m/kg as reported by Yoshioka et al.. CONCLUSION: The key
      findings of this study are as follows. (1) The minimum required joint moment for
      an STS task is essentially equivalent to the static component of the joint
      moment. (2) For fast and moderate speed movements (less than 2.5 seconds), joint
      moments increased exponentially as the movement speed increased. (3) For slow
      movements greater than 2.5 seconds, the joint moments were relatively constant.
      The results of this STS research has practical applications, especially in
      rehabilitations and exercise prescription where improved movement time is an
      intended target, since the required muscle strength can be quantitatively
      estimated.

PMID- 19849858
TI  - Early manifestation of alteration in cardiac function in dystrophin deficient mdx
      mouse using 3D CMR tagging.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by the absence of the
      cytoskeletal protein, dystrophin. In DMD patients, dilated cardiomyopathy leading
      to heart failure may occur during adolescence. However, early cardiac dysfunction
      is frequently undetected due to physical inactivity and generalized debilitation.
      The objective of this study is to determine the time course of cardiac functional
      alterations in mdx mouse, a mouse model of DMD, by evaluating regional
      ventricular function with CMR tagging. METHODS: In vivo myocardial function was
      evaluated by 3D CMR tagging in mdx mice at early (2 months), middle (7 months)
      and late (10 months) stages of disease development. Global cardiac function,
      regional myocardial wall strains, and ventricular torsion were quantified.
      Myocardial lesions were assessed with Masson's trichrome staining. RESULTS:
      Global contractile indexes were similar between mdx and C57BL/6 mice in each age
      group. Histology analysis showed that young mdx mice were free of myocardial
      lesions. Interstitial fibrosis was present in 7 month mdx mice, with further
      development into patches or transmural lesions at 10 months of age. As a result,
      10 month mdx mice showed significantly reduced regional strain and torsion.
      However, young mdx mice showed an unexpected increase in regional strain and
      torsion, while 7 month mdx mice displayed similar regional ventricular function
      as the controls. CONCLUSION: Despite normal global ventricular function, CMR
      tagging detected a biphasic change in myocardial wall strain and torsion, with an
      initial increase at young age followed by progressive decrease at older ages.
      These results suggest that CMR tagging can provide more sensitive measures of
      functional alterations than global functional indexes in dystrophin-related
      cardiomyopathies.

PMID- 19849860
TI  - Mapping quantitative trait loci (QTL) in sheep. II. Meta-assembly and
      identification of novel QTL for milk production traits in sheep.
AB  - An (Awassi x Merino) x Merino backcross family of 172 ewes was used to map
      quantitative trait loci (QTL) for different milk production traits on a framework
      map of 200 loci across all autosomes. From five previously proposed mathematical
      models describing lactation curves, the Wood model was considered the most
      appropriate due to its simplicity and its ability to determine ovine lactation
      curve characteristics. Derived milk traits for milk, fat, protein and lactose
      yield, as well as percentage composition and somatic cell score were used for
      single and two-QTL approaches using maximum likelihood estimation and regression
      analysis. A total of 15 significant (P < 0.01) and additional 25 suggestive (P <
      0.05) QTL were detected across both single QTL methods and all traits. In
      preparation of a meta-analysis, all QTL results were compared with a meta
      assembly of QTL for milk production traits in dairy ewes from various public
      domain sources and can be found on the ReproGen ovine gbrowser
      http://crcidp.vetsci.usyd.edu.au/cgi-bin/gbrowse/oaries_genome/. Many of the QTL
      for milk production traits have been reported on chromosomes 1, 3, 6, 16 and 20.
      Those on chromosomes 3 and 20 are in strong agreement with the results reported
      here. In addition, novel QTL were found on chromosomes 7, 8, 9, 14, 22 and 24. In
      a cross-species comparison, we extended the meta-assembly by comparing QTL
      regions of sheep and cattle, which provided strong evidence for synteny
      conservation of QTL regions for milk, fat, protein and somatic cell score data
      between cattle and sheep.

PMID- 19849861
TI  - An optimization framework for unsupervised identification of rare copy number
      variation from SNP array data.
AB  - Copy number variants (CNVs) have roles in human disease, and DNA microarrays are
      important tools for identifying them. In this paper, we frame CNV identification
      as an objective function optimization problem. We apply our method to data from
      hundreds of samples, and demonstrate its ability to detect CNVs at a high level
      of sensitivity without sacrificing specificity. Its performance compares
      favorably with currently available methods and it reveals previously unreported
      gains and losses.

PMID- 19849862
TI  - Direct calibration of PICKY-designed microarrays.
AB  - BACKGROUND: Few microarrays have been quantitatively calibrated to identify
      optimal hybridization conditions because it is difficult to precisely determine
      the hybridization characteristics of a microarray using biologically variable
      cDNA samples. RESULTS: Using synthesized samples with known concentrations of
      specific oligonucleotides, a series of microarray experiments was conducted to
      evaluate microarrays designed by PICKY, an oligo microarray design software tool,
      and to test a direct microarray calibration method based on the PICKY-predicted,
      thermodynamically closest nontarget information. The complete set of microarray
      experiment results is archived in the GEO database with series accession number
      GSE14717. Additional data files and Perl programs described in this paper can be
      obtained from the website http://www.complex.iastate.edu under the PICKY Download
      area. CONCLUSION: PICKY-designed microarray probes are highly reliable over a
      wide range of hybridization temperatures and sample concentrations. The
      microarray calibration method reported here allows researchers to experimentally
      optimize their hybridization conditions. Because this method is straightforward,
      uses existing microarrays and relatively inexpensive synthesized samples, it can
      be used by any lab that uses microarrays designed by PICKY. In addition, other
      microarrays can be reanalyzed by PICKY to obtain the thermodynamically closest
      nontarget information for calibration.

PMID- 19849863
TI  - Expression profiling identifies genes involved in neoplastic transformation of
      serous ovarian cancer.
AB  - BACKGROUND: The malignant potential of serous ovarian tumors, the most common
      ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors
      to frankly invasive cancers. Given the uncertainty about the relationship between
      these different forms, we compared their patterns of gene expression. METHODS:
      Expression profiling was carried out on samples of 7 benign, 7 LMP and 28
      invasive (moderate and poorly differentiated) serous tumors and four whole normal
      ovaries using oligonucleotide microarrays representing over 21,000 genes.
      RESULTS: We identified 311 transcripts that distinguished invasive from benign
      tumors, and 20 transcripts that were significantly differentially expressed
      between invasive and LMP tumors at p < 0.01 (with multiple testing correction).
      Five genes that were differentially expressed between invasive and either benign
      or normal tissues were validated by real time PCR in an independent panel of 46
      serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A
      and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and
      LMP compared with benign and normal tissues. Over-expression of WNT7A in an
      ovarian cancer cell line led to increased migration and invasive capacity.
      CONCLUSION: These results highlight several genes that may play an important role
      across the spectrum of serous ovarian tumorigenesis.

PMID- 19849864
TI  - Efficacies of the new paclitaxel-eluting Coroflex Please stent in percutaneous
      coronary intervention; comparison of efficacy between Coroflex Please and Taxus
      (ECO-PLEASANT) trial: study rationale and design.
AB  - BACKGROUND: Previous randomized trials have showed the superiority of Paclitaxel
      eluting stent over bare metal stent in angiographic and clinical outcomes.
      Coroflex Please stent is a newly developed drug eluting stent using the Coroflex
      stent platform combined with the drug paclitaxel contained in a polymer coating.
      PECOPS I trial, one-arm observational study, showed that the clinical and
      angiographic outcomes of Coroflex Please stent were within the range of those of
      Taxus, the 1st generation paclitaxel-eluting stent (PES). However, there have
      been no studies directly comparing the Coroflex Please stent with the Taxus
      Liberte stent that is the newest version of Taxus. Therefore, prospective,
      randomized trial is required to demonstrate the non-inferiority of Coroflex
      Please stent compared with Taxus Liberte stent in a head-to-head manner. METHODS:
      In the comparison of Efficacy between COroflex PLEASe ANd Taxus stent(ECO
      PLEASANT) trial, approximately 900 patients are being prospectively and randomly
      assigned to the either type of Coroflex Please stent and Taxus Liberte stent via
      web-based randomization. The primary endpoint is clinically driven target vessel
      revascularization at 9 months. The secondary endpoints include major cardiac
      adverse events, target vessel failure, stent thrombosis and angiographic efficacy
      endpoints. DISCUSSION: The ECO-PLEASANT trial is the study not yet performed to
      directly compare the efficacy and safety of the Coroflex Please versus Taxus
      Liberte stent. On the basis of this trial, we will be able to find out whether
      the Coroflex Please stent is non-inferior to Taxus Liberte stent or not. TRIAL
      REGISTRATION: ClinicalTrials.gov number, NCT00699543.

PMID- 19849866
TI  - Pemphigus vulgaris in pregnancy: analysis of current data on the management and
      outcomes.
AB  - OBJECTIVES: The occurrence of pemphigus vulgaris (PV) during pregnancy is rare.
      The purpose of this review was to describe management of PV in the mother, and
      report maternal and perinatal outcomes associated with the disease. DATA SOURCES:
      A search of PubMed was conducted using the phrases "pemphigus and pregnancy" and
      "neonatal pemphigus." The bibliographies of retrieved articles were also searched
      for relevant reports. Only articles in English and in which the diagnosis of
      pemphigus had been made on the basis of histology or immunopathology were
      included. TABULATION, INTEGRATION, AND RESULTS: In 38 reports, pregnancies from
      49 women with PV were described. Among the 40 patients in whom clinical profiles
      were provided, 33 had active disease and 7 were disease free. Prednisone was used
      in 37 of 49 (75%) patients with doses ranging from 5 to 300 mg/day (mean 152.5
      mg). Concomitant therapies included plasmapheresis, plasma exchange, and dapsone
      in 1 patient each, and azathioprine in 5. Of the 44 live births, 20 (45%)
      neonates had PV lesions at birth and 24 (55%) were lesion-free. Five stillbirths
      were reported. In all neonates, PV lesions resolved within 1 to 4 weeks, either
      spontaneously or with mild topical corticosteroids treatment. Of the 5
      intrauterine deaths, 1 was due to umbilical cord prolapse, 1 attributed to
      placental dysfunction, and 1 to cytomegalovirus pneumonitis. In the remaining 2,
      the cause was unknown. One neonate died 2 days after delivery due to meconium
      aspiration syndrome. Thus the aggregate perinatal mortality rate was 12% (6/49).
      CONCLUSIONS: The outcome of pregnancies complicated by pemphigus is generally
      good, but achieving good outcomes likely depends on the collaborative efforts of
      the dermatologist and obstetrician. The available data suggest that the rate of
      perinatal mortality is increased, but these data may be subject to publication
      bias. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING
      OBJECTIVES: After completion of this educational activity, the participant should
      be better able to describe appropriate medical therapies for pemphigus vulgaris
      complicating pregnancy, and plan the management of pregnancies complicated by
      pemphigus vulgaris.

PMID- 19849865
TI  - Determining a low disease activity threshold for decision to maintain disease
      modifying antirheumatic drug treatment unchanged in rheumatoid arthritis
      patients.
AB  - INTRODUCTION: The aim of this study was to determine a low disease activity
      threshold--a 28-joint disease activity score (DAS28) value--for the decision to
      maintain unchanged disease-modifying antirheumatic drug (DMARD) treatment in
      rheumatoid arthritis patients, based on expert opinion. METHODS: Nine hundred and
      sixty-seven case scenarios with various levels for each component of the DAS28
      (resulting in a disease activity score between 2 and 3.2) were presented to 44
      panelists. For each scenario, panelists had to decide whether or not DMARD
      treatment (excluding steroids) could be maintained unchanged. In each scenario,
      for decision, the participants were given the DAS28 parameters, without knowledge
      of the resultant DAS28. The relationship between panelists' decision, DAS28
      value, and components of the score were analysed by multiple logistic regression
      analysis. Each panelist analysed 160 randomised scenarios. Intra-rater and inter
      rater reproducibility were assessed. RESULTS: Forty-four panelists participated
      in the study. Inter-panelist agreement was good (kappa = 0.63; 95% confidence
      interval = 0.61 to 0.65). Intra-panelist agreement was excellent (kappa = 0.87;
      95% confidence interval = 0.82 to 0.92). Quasi-perfect agreement was observed for
      DAS28 < or = 2.4, less pronounced between 2.5 and 2.9, and almost no agreement
      for DAS28 > 3.0. For values below 2.5, panelists agreed to maintain unchanged
      DMARDs; for values above 2.5, discrepancies occurred more frequently as the DAS28
      value increased. Multivariate analysis confirmed the relationship between
      panelist's decision, DAS28 value and components of the DAS28. Between DAS28 of
      2.4 and 3.2, a major determinant for panelists' decision was swollen joint count.
      Female and public practice physicians decided more often to maintain treatment
      unchanged. CONCLUSIONS: As a conclusion, panelists suggested that in clinical
      practice there is no need to change DMARD treatment in rheumatoid arthritis
      patients with DAS28 < or = 2.4.

PMID- 19849867
TI  - Lipid peroxidation and antioxidant status in preeclampsia: a systematic review.
AB  - BACKGROUND: Preeclampsia is characterized by increased lipid peroxidation and
      diminished antioxidant capacity; however, there is no consensus as to the extent
      of these conditions. OBJECTIVE: To assess the association of lipid peroxidation
      and antioxidant status with preeclampsia quantitatively using meta-analysis.
      DESIGN: Systematic review and meta-analysis. SEARCH STRATEGY: Studies were
      identified by performing an extensive search using BIOSIS (1986-2007), EMBASE
      (1986-2007), Medline (1986-2007), and the Cochrane database. DATA ANALYSIS:
      Standardized mean differences (SMD) with 95% confidence intervals (CI) were used
      in the meta-analysis and sources of heterogeneity were examined. MAIN RESULTS: In
      the included studies, the overall SMD was a 1.21 nmol/mL increase in serum
      malondialdehyde in preeclampsia cases compared to controls (95% CI: 0.76, 1.66).
      Overall, total serum thiobarbituric acid-reactive substances SMD were 1.62
      nmol/mL greater in cases than in controls (95% CI: 0.27, 2.96). The overall
      estimate SMD for serum vitamin E was 1.12 nmol/mL less in cases than controls
      (95% CI: -1.77, -0.48) and vitamin C SMD overall estimate was -0.53 (95%CI: 
      1.03, -0.02), significantly lower in cases compared with controls. The overall
      SMD for erythrocyte superoxide dismutase was -2.37 (95% CI: -4.76, 0.03), a
      marginally significant decrease in cases versus controls. CONCLUSIONS:
      Established preeclampsia is associated with increased concentrations of oxidative
      stress markers including lipid peroxidation products, and a reduction in
      antioxidant concentrations. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians. LEARNING OBJECTIVES: After completion of this educational
      activity, the participant should be better able to describe the pattern of
      oxidative stress markers associated with preeclampsia, and interpret the
      available literature as it relates to oxidative stress and preeclampsia.

PMID- 19849868
TI  - The role of genes in the development of Mullerian anomalies: where are we today?
AB  - Recent studies claim that researchers are challenged to find out the pathogenesis
      of the congenital anomalies of the female reproductive tract. Their frequency is
      estimated to be between 0.1% and 3% of live births in humans. During the
      experiments a number of genes were detected to contribute to the formation and
      development of the female reproductive tract. This review article aims to report
      these genes, as they probably play a significant role in the pathology of the
      reproductive tract in females. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians. LEARNING OBJECTIVES: After completion of this educational
      activity, the participant should be better able to explain the genetic basis of
      Mullerian abnormalities, give examples of the complexity of the genetic basis
      behind a variety of mechanisms of disease, and recall the embryology of the
      female reproductive tract.

PMID- 19849869
TI  - Quantitative differences in intestinal Faecalibacterium prausnitzii in obese
      Indian children.
AB  - Gut bacteria contribute to energy conservation in man through their ability to
      ferment unabsorbed carbohydrate. The present study examined the composition of
      predominant faecal microbiota in obese and non-obese children. The participants
      (n 28) aged 11-14 years provided fresh faecal samples and completed a dietary
      survey consisting of 24 h diet recall and a FFQ of commonly used foods taken over
      the previous 3 months. Faecal bacteria were quantitated by real-time PCR using
      primers targeted at 16S rDNA. Of the participants, fifteen (seven female) were
      obese, with median BMI-for-age at the 99th percentile (range 97 to>99) while
      thirteen participants (seven female) were normal weight, with median BMI-for age
      being at the 50th percentile (range 1-85). Consumption of energy, carbohydrates,
      fat and protein was not significantly different between the obese and non-obese
      participants. There was no significant difference between the two groups in
      faecal levels of Bacteroides-Prevotella, Bifidobacterium species, Lactobacillus
      acidophilus group or Eubacterium rectale. Levels of Faecalibacterium prausnitzii
      were significantly higher in obese children than in non-obese participants (P =
      0.0253). We concluded that the finding of increased numbers of F. prausnitzii in
      the faeces of obese children in south India adds to the growing information on
      alterations in faecal microbiota in obesity.

PMID- 19849870
TI  - Wanted: specific nutritional biomarkers for food consumption for the study of its
      protective role in health.

PMID- 19849871
TI  - Role of zinc along with ascorbic acid and folic acid during long-term in vitro
      albumin glycation.
AB  - The present study aimed to investigate the role of Zn alone and in the presence
      of ascorbic acid (AA) and folic acid (FA) in albumin glycation. Glycation was
      performed by incubations of bovine serum albumin with glucose at 37 degrees C
      along with Zn, AA or FA separately and Zn + AA or Zn + FA for 150 d. Glycation
      mediated modifications were monitored as fluorescence of advanced glycation
      endproducts, carbonyl formation, beta aggregation (thioflavin T and Congo red
      dyes), albumin-bound Zn, thiol groups and glycated aggregate's toxicity in HepG2
      cells. Zn inhibited glycation and beta aggregation, probably due to observed
      higher protein-bound Zn. It also protected protein thiols and increased cell
      survival. AA and FA enhanced glycation, which was lowered in Zn-co-incubated
      samples. FA increased albumin-bound Zn and showed maximum cell survival. Although
      these results warrant further in vivo investigation, the present data help in the
      understanding of the interplay of Zn with micronutrients in albumin glycation.

PMID- 19849872
TI  - Stenosis of the main stem of the left coronary artery in a teenager with
      Takayasu's arteritis.
AB  - Coronary arterial involvement is rare in Takayasu's arteritis. We describe
      successful coronary arterial bypass grafting in a 15 year teenager with
      Takayasu's arteritis and unstable angina because of stenosis of the main stem of
      the left coronary artery.

PMID- 19849873
TI  - N-terminal pro-B-type natriuretic peptide and ventricular dysfunction in children
      and adolescents.
AB  - Our aim was further to clarify the diagnostic usefulness of N-terminal pro-B-type
      natriuretic peptide for detecting ventricular dysfunction in children, and its
      correlation with myocardial performance index and New York University Pediatric
      Heart Failure Index score. We also hypothesized that the level of this
      natriuretic peptide in the serum could predict the severity of diastolic
      abnormalities in children with cardiac failure. We enrolled 99 patients, aged
      from 3 months to 16 years, who had been referred for echocardiography to evaluate
      ventricular function. Echocardiographic evidence of left ventricular systolic and
      diastolic dysfunction was found in 20 and 42 patients, respectively. We
      classified these patients as having impaired relaxation, seen in 12 patients,
      pseudonormal patterns seen in 19 patients, and restrictive-like patterns of
      filling seen in 11 patients. The mean of the log-transformed values for N
      terminal pro-B-type natriuretic peptide increased significantly according to the
      severity of diastolic dysfunction (p = 0.003, p = 0.022, p < 0.0001). A value of
      178 pg/ml had a sensitivity of 88% and specificity of 81% for detecting abnormal
      diastolic function (p < 0.0001). Furthermore, the log-transformed values
      correlated with myocardial performance index (p < 0.0001) in a positive manner,
      and the levels increased significantly according to New York University Pediatric
      Heart Failure Index score, showing a linear correlation with a robust r value for
      regression (r = 0.89, p < 0.0001). Our findings suggest that higher levels of the
      peptide, having a good correlation with New York University Pediatric Heart
      Failure Index score and myocardial performance index, might be a suitable marker
      to rule out ventricular diastolic dysfunction in children.

PMID- 19849874
TI  - Adherence to treatment among children with cardiac disease.
AB  - OBJECTIVE: Our purpose was to review the literature with respect to issues of
      adherence to treatment among children with congenital and acquired cardiac
      disease. MATERIALS AND METHODS: Databases used for this review included MEDLINE,
      Pub Med's Single Citation Manager, Cochrane Library, Cochrane Central Register of
      Controlled Trials, Scopus, and Google Scholar. We did not use any restrictions on
      date when locating peer-reviewed articles published worldwide through December of
      2008. RESULTS: There exists a lack of published research regarding adherence to
      medical treatment for children with cardiac conditions. Of the few published
      studies, rates of adherence for children with congenital and acquired cardiac
      disease ranged from a high of 96% for an in-patient exercise programme, to a low
      of 33% among those who made all of their medical appointments. Risk factors for
      nonadherence included older age, one as opposed to two parents in the home, lack
      of emotional availability of parents, smoking, sedentary lifestyle, use of
      illicit drugs, presence of tattoos, and multiple body piercings. Clinical
      outcomes associated with non adherence in the population of children undergoing
      transplantation included mortality, acute episodes of rejection, lower levels of
      Cyclosporine A, and lower values for the International Normalised Ratio of
      prothrombin. CONCLUSIONS: For children with congenital and acquired heart
      disease, the challenges of adherence to treatment can often be overwhelming.
      Recommendations designed to maximize the impact and scientific rigour of future
      studies include obtaining quantitative and qualitative measures of adherence,
      identifying primary and secondary endpoints, emphasizing factors of interest,
      planning studies with sufficient power to impact on the adherence to treatment,
      and developing epidemiologic foundations.

PMID- 19849875
TI  - Poor outcome for patients with totally anomalous pulmonary venous connection and
      functionally single ventricle.
AB  - Totally anomalous pulmonary venous connection, when also associated with a
      functionally univentricular connection, is known to have a poor outcome. We
      retrospectively analysed results for 19 patients undergoing surgery for this
      combination of lesions between 1995 and February 2009.Of the patients, 12 were
      neonates, with 11 presenting with signs of pulmonary venous obstruction. In 3
      patients, a modified Blalock-Taussig shunt had been constructed. The dominant
      ventricle was of right ventricular morphology in 17 of the 19 patients, and
      double inlet was present in all bar 1. Pulmonary atresia or stenosis was found in
      14 patients, a common atrioventricular junction in 14 patients, and isomerism of
      the right atrial appendages in 12 patients, respectively. Comprehensive Aristotle
      scores ranged from 14 to 23.50. The mean was 16.55, with a standard deviation of
      2.19. Pulmonary venous rerouting was combined in 6 patients with construction of
      a modified Blalock-Taussig, in 4 with banding of the pulmonary trunk, in another
      4 with a bidirectional Glenn anastomosis, in 3 with creation of a total cavo
      pulmonary connection, and in 1 each with enlargement of the right ventricular
      outflow tract and the Norwood procedure. Of the cohort, 8 patients died early due
      to pulmonary hypertension, with all patients having Aristotle scores of at least
      18 points dying. Among the 11 early survivors, 5 needed mechanical ventilation
      for over a week, but 5 patients died later, 3 due to pulmonary hypertension and 2
      due to infection. Actuarial survival stabilized at 31.6%, with standard error of
      10.7%, from one year onwards. Conversion to the Fontan circulation was successful
      in 5 patients.Our experience confirms that totally anomalous pulmonary venous
      connection, when associated with the functionally univentricular arrangement,
      carries one of the worst outcomes in current surgical practice. Use of the
      Aristotle comprehensive complexity scores effectively discriminates those
      patients with this condition at particularly high risk.

PMID- 19849876
TI  - Valve-sparing replacement of the aortic root for a 2-year-old child with Loeys
      Dietz syndrome.
AB  - Loeys-Dietz syndrome is a newly recognized constellation that presents with
      aortic aneurysm or dissection similar to Marfan's syndrome. We describe
      successful surgical treatment in a 2-year-old with the syndrome in whom we
      performed a valve-sparing replacement of the aortic root because of significant
      dilation of the aortic root and the ascending aorta.

PMID- 19849877
TI  - Stress imaging in congenital cardiac disease.
AB  - In patients with coronary arterial disease, stress imaging is able to demonstrate
      abnormalities in the motion of the ventricular walls, and abnormalities in
      coronary arterial perfusion not apparent at rest. It can also provide information
      on prognostic factors. In patients with congenitally malformed hearts, stress
      imaging is used to determine contractile reserve, abnormalities of mural motion,
      and global systolic function, but also to assess diastolic and vascular function.
      In most of these patients, stress is usually induced using pharmacological
      agents, mainly dobutamine given in varying doses. The clinical usefulness of
      abnormal responses to the stress induced in such patients has to be addressed in
      follow-up studies. The abnormal stress might serve as surrogate endpoints,
      predicting primary endpoints at an early stage, which are useful for
      stratification of risk in this population of growing patients. We review here the
      stress imaging studies performed to date in patients with congenitally malformed
      hearts, with a special emphasis on echocardiography and cardiac magnetic
      resonance imaging.

PMID- 19849878
TI  - Diagnosis and management of congenital right pulmonary venous atresia.
AB  - Congenital unilateral pulmonary venous atresia is a rare anatomical defect.
      Patients present with pulmonary symptoms, and diagnosis may be elusive. Pulmonary
      arterial wedge angiography is the gold standard with which to achieve diagnosis,
      and surgical intervention is often required for symptomatic patients.

PMID- 19849879
TI  - Successful treatment of a thrombus in the left aortic coronary sinus in a child
      with systemic lupus erythematosus.
AB  - We report our experience in a 12 year old boy referred with suspected myocardial
      infarction. He has previously been diagnosed with systemic lupus erythematosus,
      and was being treated with steroids. Echocardiographic examination revealed a
      thrombus in the left aortic coronary sinus of Valsalva partially occluding the
      orifice of the left coronary artery. The thrombosis was successfully treated by
      venous thrombolysis using recombinant tissue plasminogen activator.

PMID- 19849880
TI  - Differential engagement of cognitive and affective neural systems in pediatric
      bipolar disorder and attention deficit hyperactivity disorder.
AB  - This fMRI study investigates the neural bases of cognitive control of emotion
      processing in pediatric bipolar disorder (PBD) and attention deficit
      hyperactivity disorder (ADHD). Seventeen un-medicated PBD patients, 15 un
      medicated ADHD patients, and 14 healthy controls (HC) (mean age = 13.78 +/- 2.47)
      performed an emotional valence Stroop Task, requiring them to match the color of
      an emotionally valenced word to the color of either of two adjacent circles. Both
      patient groups responded significantly slower than HC, but there were no group
      differences in accuracy. A voxel-wise analysis of variance on brain activation
      revealed a significant interaction of group by word valence [F(2,41) = 4.44; p =
      .02]. Similar group differences were found for negative and positive words. For
      negative versus neutral words, both patient groups exhibited greater activation
      in dorsolateral prefrontal cortex (DLPFC) and parietal cortex relative to HC. The
      PBD group exhibited greater activation in ventrolateral prefrontal cortex (VLPFC)
      and anterior cingulate cortex (ACC) relative to HC. The ADHD group exhibited
      decreased VLPFC activation relative to HC and the PBD group. During cognitive
      control of emotion processing, PBD patients deployed the VLPFC to a greater
      extent than HC. The ADHD patients showed decreased VLPFC engagement relative to
      both HC and PBD patients.

PMID- 19849881
TI  - Attentional networks efficiency in preterm children.
AB  - Recent studies have reported specific executive and attentional deficits in
      preterm children. However, the majority of this research has used multidetermined
      tasks to assess these abilities, and the interpretation of the results lacks an
      explicit theoretical backdrop to better understand the origin of the difficulties
      observed. In the present study, we used the Child Attention Network Task (Child
      ANT; Rueda et al. 2004) to assess the efficiency of the alerting, orienting and
      executive control networks. We compared the performance of 25 preterm children
      (gestational age < or = 32 weeks) to 25 full-term children, all between 5(1/2)
      and 6(1/2) years of age. Results showed that, as compared to full-term children,
      preterm children were slower on all conditions of the Child ANT and had a
      specific deficit in executive control abilities. We also observed a significantly
      higher correlation between the orienting and executive control networks in the
      preterm group, suggesting less differentiation of these two networks in this
      population.

PMID- 19849882
TI  - Examining predictors of reaction times in children with ADHD and normal controls.
AB  - A microanalysis of task events in a common go/no-go task was completed to examine
      how task events impact individual reaction times. Predictors of long reaction
      times were analyzed to better understand increased intra-individual variability
      (IIV) among children with ADHD compared with normal controls. Sixty-five children
      with ADHD and 65 normal controls matched on gender, ethnicity, and age completed
      a go/no-go task. Children across both groups were slower before and after
      omission errors than all other trials. They were also slower on the trial before
      successfully inhibiting their response to no-go trials. Children with ADHD
      exhibited a pronounced slowing on trials prior to omission errors and trials
      prior to successful inhibitions compared with the normal control group. Pre-error
      slowing in children with ADHD may represent the beginning stages of attentional
      disengagement that subsequently results in the absence of responding (i.e.,
      errors of omission or successful inhibition). While these event-related increases
      in reaction time explain some of the increased IIV observed in children with
      ADHD, the removal of these trials did not remove the pronounced between-group
      differences in IIV, suggesting that additional unmeasured processes are
      contributing to IIV in children with ADHD.

PMID- 19849884
TI  - Variation in the helminth community structure of Thrichomys pachyurus (Rodentia:
      Echimyidae) in two sub-regions of the Brazilian Pantanal: the effects of land use
      and seasonality.
AB  - The Pantanal is a large ecosystem located in South America. This preserved area
      is seasonally flooded due to abundant rainfall during the summer and the
      subsequent overflow of the Paraguai River. In this paper, we examine the helminth
      community structure in the wild rodent Thrichomys pachyurus during the wet and
      dry seasons in two locations of the preserved and cattle ranching areas in the
      Southern Pantanal. We identified 12 species of helminth, and, although we did not
      find any differences in species richness between locations within the Pantanal,
      we found that richness was higher during the wet season. Helminth species were
      largely aggregated in both farm locations and during seasons. The most common
      helminth species were more abundant during the dry season than during the wet
      season, which may have been due to the increased habitat availability and rodent
      population increase. The intensity of the infection also followed the same
      pattern for most helminths. The trichostrongylids (Heligmostrongylus crucifer, H.
      almeidai and Pudica cercomysi) were dominant at both farm locations. The land use
      of each area was not correlated with helminth diversity. However, species
      composition of the helminth community of T. pachyurus differed between locations
      and may be correlated with environmental differences between the habitats. The
      seasonality of the Pantanal was highly correlated with helminth parasitism in T.
      pachyurus.

PMID- 19849883
TI  - Cognitive development after traumatic brain injury in young children.
AB  - The primary aims of this study were to examine post-injury cognitive development
      in young children with traumatic brain injury (TBI) and to investigate the role
      of the proximal family environment in predicting cognitive outcomes. Age at
      injury was 3-6 years, and TBI was classified as severe (n = 23), moderate (n =
      21), and complicated mild (n = 43). A comparison group of children who sustained
      orthopedic injuries (OI, n = 117) was also recruited. Child cognitive assessments
      were administered at a post-acute baseline evaluation and repeated at 6, 12, and
      18 months post-injury. Assessment of the family environment consisted of baseline
      measures of learning support and stimulation in the home and of parenting
      characteristics observed during videotaped parent-child interactions. Relative to
      the OI group, children with severe TBI group had generalized cognitive
      deficiencies and those with less severe TBI had weaknesses in visual memory and
      executive function. Although deficits persisted or emerged across follow-up, more
      optimal family environments were associated with higher scores for all injury
      groups. The findings confirm other reports of poor recovery of cognitive skills
      following early childhood TBI and suggest environmental influences on outcomes.

PMID- 19849885
TI  - Blood parasitaemia in a high latitude flexible breeder, the white-winged
      crossbill, Loxia leucoptera: contribution of seasonal relapse versus new
      inoculations.
AB  - We measured seasonal changes in the prevalence of haematozoa (Leucocytozoon
      fringillinarum, Haemoproteus fringillae, and Trypanosoma avium) in free-ranging
      White-winged Crossbills, Loxia leucoptera, over 1.5 year in Fairbanks, Alaska,
      USA. This prevalence was low during early winter. L. fringillinarum prevalence
      increased in late winter/early spring, in the absence of vectors, suggesting
      relapse of latent infection. By contrast, the prevalence of T. avium and H.
      fringillae did not increase until mid-spring, coincident with the emergence of
      putative vectors and suggestive of new inoculations. The winter breeding period
      was not associated with lower body condition or elevated blood
      heterophil/lymphocyte ratios than the summer post-breeding period. Thus, birds
      unlikely perceived their breeding effort as particularly stressful. Adult males
      in May and June had low plasma testosterone and their blood prevalence of L.
      fringillinarum, but not other haemoparasites, was higher than in adult females.
      This difference may have resulted from sex differences in behaviour and/or
      plumage colouration - bright red in males, dull green/yellow in females. Species
      in which reproduction and vector abundance are seasonally dissociated may
      constitute important models for investigating the respective contribution of
      reproductive hormones, breeding effort, and vector abundance to patent and latent
      hemoparasitic infections and to new inoculations.

PMID- 19849886
TI  - Epigenetic transcriptional gene silencing in Entamoeba histolytica: insight into
      histone and chromatin modifications.
AB  - We have previously discovered a unique mechanism of epigenetic transcriptional
      gene silencing in the Entamoeba histolytica trophozoites of strain HM-1:IMSS that
      resulted in the persistent downregulation of the amoebapore A (ap-a) gene, and
      that could be successfully applied to silence other virulence genes (cpA5, lgl1).
      In order to understand how the silencing is maintained throughout generations, we
      analysed whether modifications occurred at the chromatin level. Chromatin
      immunoprecipitation assays were done with antibodies specific to the methylated
      lysine 4 of E. histolytica histone H3. When the genes were in a transcriptionally
      silent state, the methylation levels of H3K4 in their coding region were
      significantly reduced. In contrast, the levels of core histone H3 were
      consistently higher in the silenced genes. Controlled chromatin digestion with
      micrococcal nuclease was used to assess changes in nucleosome compaction. We
      found a significant resistance to digestion in the promoter region of the
      silenced ap-a and cpA5 genes as compared to the parental strain that expresses
      those genes. Our data lend further support to the idea that histone modifications
      and heterochromatin formations are at the basis of the transcriptional silencing
      of genes in E. histolytica.

PMID- 19849887
TI  - Molecules and morphology reveal cryptic variation among digeneans infecting
      sympatric mullets in the Mediterranean.
AB  - We applied a combined molecular and morphological approach to resolve the
      taxonomic status of Saccocoelium spp. parasitizing sympatric mullets (Mugilidae)
      in the Mediterranean. Eight morphotypes of Saccocoelium were distinguished by
      means of multivariate statistical analyses: 2 of Saccocoelium obesum ex Liza
      spp.; 4 of S. tensum ex Liza spp.; and 2 (S. cephali and Saccocoelium sp.) ex
      Mugil cephalus. Sequences of the 28S and ITS2 rRNA gene regions were obtained for
      a total of 21 isolates of these morphotypes. Combining sequence data analysis
      with a detailed morphological and multivariate morphometric study of the
      specimens allowed the demonstration of cryptic diversity thus rejecting the
      hypothesis of a single species of Saccocoelium infecting sympatric mullets in the
      Mediterranean. Comparative sequence analysis revealed 4 unique genotypes, thus
      corroborating the distinct species status of Saccocoelium obesum, S. tensum and
      S. cephali and a new cryptic species ex Liza aurata and L. saliens recognized by
      its consistent morphological differentiation and genetic divergence. However, in
      spite of their sharp morphological difference the 2 morphotypes from M. cephalus
      showed no molecular differentiation and 4 morphotypes of S. tensum were
      genetically identical. This wide intraspecific morphological variation within S.
      tensum and S. cephali suggests that delimiting species of Saccocoelium using
      solely morphological criteria will be misleading.

PMID- 19849888
TI  - Experimental transmission of malacosporean parasites from bryozoans to common
      carp ( Cyprinus carpio) and minnow ( Phoxinus phoxinus).
AB  - To address whether a fish host is involved in the life cycles of malacosporeans
      of the genus Buddenbrockia, cohabitation experiments with different bryozoan and
      fish species were conducted. Samples were analysed by malacosporean-specific PCR,
      partial sequencing of the 18S rDNA, and light and electron microscopy. Co
      habitation challenges with bryozoans resulted in malacosporean infections
      detected mainly in the kidney of common carp (Cyprinus carpio) and minnow
      (Phoxinus phoxinus). Sequences of the minnow parasite and of worm-like
      Buddenbrockia stages in Plumatella repens were identical and showed 99.5%
      similarity to Buddenbrockia plumatellae and 96.3% similarity to the sequence
      obtained from carp. One sample, comprising 4-5 zooids of statoblast-raised
      bryozoans cohabitated with infected carp was PCR-positive, but no overt infection
      could be observed in the remaining colony. Light and electron-microscopy of
      kidney samples of infected minnows revealed single cells within kidney tubules,
      whereas in carp, sporogonic stages were found in kidney tubules. Phylogenetic
      analysis of the Buddenbrockia spp. known to date placed the carp-infecting
      species at the base of the B. plumatellae clade, but low posterior probability
      makes this node questionable. The present study showed that Buddenbrockia spp.
      were able to infect cyprinid fish, showing stages in kidney-tubules strikingly
      similar to those of T. bryosalmonae.

PMID- 19849890
TI  - Decay of similarity with host phylogenetic distance in parasite faunas.
AB  - Exponential decay in community similarity as a function of distance is a
      ubiquitous phenomenon in biogeography. Thus, for parasite communities, pairwise
      similarity decreases with increasing geographical distance between host
      populations. This biogeographical rule should also apply along other dimensions
      characterizing the separation between communities. Since host-switching and
      phylogenetic affinities among host species affect the evolution of parasite
      faunas across host phylogenetic space the same way as dispersal and environmental
      gradients affect the assembly of local communities in geographical space, an
      exponential decay in similarity of parasite faunas with increasing host
      phylogenetic distance should be observed. This prediction is tested using data on
      metazoan parasites of 45 species of Canadian freshwater fishes belonging to 5
      families. Across all host species, pairwise similarity in the composition of
      parasite faunas decayed exponentially, though not strongly, with increasing
      phylogenetic distance between hosts (measured as the number of substitutions per
      site along DNA sequences). A meta-analysis of correlations computed for separate
      fish families indicates only a very weak overall relationship. Data distribution
      indicates that phylogenetically close host species tend to share many of their
      parasites, while phylogenetically distant hosts have roughly equal chances of
      harbouring very similar or very dissimilar parasite faunas. The same pattern was
      seen when monogenean and trematode parasites were analysed separately, whereas no
      significant decay was observed for cestodes or nematodes, suggesting different
      patterns of host-switching and parasite colonization among these taxa. The
      results show that similarity in species composition decreases, though weakly,
      with increasing distance in the same manner in phylogenetic space as it does in
      geographical space.

PMID- 19849889
TI  - Transplacental transfer of filarial antigens from Wuchereria bancrofti-infected
      mothers to their offspring.
AB  - OBJECTIVE: Maternal infection has been considered to be a risk factor for
      filarial infection in offspring. In order to examine the influence of maternal
      infection in neonates, we have determined the prevalence of circulating filarial
      antigen (CFA) and anti-filarial antibodies in 119 maternal and corresponding cord
      blood samples collected from an area endemic for bancroftian filariasis. METHOD:
      Prevalence of antigenaemia was detected using Og4C3 circulating filarial antigen
      enzyme-linked immunosorbent assay. The presence of microfilariae was determined
      by filtration of a 1 ml sample through a Nuclepore membrane. Antibody isotypes
      (IgG, IgM, and IgE) to filarial antigen (Setaria digitata antigenic extract) were
      determined by enzyme linked immunosorbent assay (ELISA). RESULTS: Microfilariae
      were detected in 14 cases (11.8%), whereas the Og4C3 assay could detect filarial
      antigen in 44.5% of pregnant mothers. Interestingly, 24.5% of samples born from
      CFA-positive mothers were found positive for CFA. None of the cord samples from
      CFA-negative mothers were found positive for CFA. No significant difference was
      observed in prevalence of filarial-specific IgG, IgM and IgE antibodies in CFA
      positive and negative mothers. IgG antibody was detected in 60.5% of maternal and
      21.8% of cord samples. IgG antibody in the cord does not differ with the antigen
      status of the mother. In contrast IgM and IgE antibody prevalence was
      significantly higher in cord from infected mothers than non-infected mothers
      (11.3% vs 0 for IgM, 24.5% vs 3.03% for IgE). CONCLUSION: Our study demonstrates
      the transplacental transfer of circulating filarial antigen from mother to cord.
      Filaria-specific IgM and IgE antibodies were higher in cord blood from infected
      mothers than from non-infected mothers. The findings of the study provide
      additional circumstantial evidence for pre-natal sensitization to filarial
      antigens developed in utero.

PMID- 19849892
TI  - Improvement of executive functions in boys with attention deficit hyperactivity
      disorder: an open-label follow-up study with once-daily atomoxetine.
AB  - Atomoxetine is efficacious in reducing symptoms of attention deficit
      hyperactivity disorder (ADHD) but its effect on executive functions needs more
      investigation. We examined the effect of atomoxetine on a wide range of non
      verbal executive functions among 30 drug-naive male patients with DSM-IV ADHD,
      aged 8-16 yr, in an open-label 12-wk atomoxetine treatment trial. Before
      administration of atomoxetine, the participants were assessed by psychiatric
      interviews, the WISC-III, and the tasks involving executive functions of the
      Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra
      dimensional/Extra-dimensional Shifts (IED), Rapid Visual Information Processing
      (RVIP), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of
      Cambridge (SOC); and reassessed at weeks 4 and 12. All the raw scores of the
      CANTAB were transformed to z scores based on a normative sample of 180 children
      aged 8-16 yr. Results showed significant improvement in executive functions after
      treatment with atomoxetine for 4 wk or 12 wk including improved shifting and
      flexibility of attention in the IED; improved spatial short-term memory in the
      SSP; improved sustained attention and increased response inhibition in the RVIP;
      improved spatial working memory in the SWM; and improved spatial planning and
      problem solving in the SOC. Our findings suggested that atomoxetine was
      associated with significant improvement in various non-verbal executive functions
      among boys with ADHD, in addition to its well-known efficacy in ADHD-related
      symptom reductions. However, owing to lack of a placebo-controlled trial design,
      the findings should be interpreted with caution that changes in performance may
      be due to practice effects.

PMID- 19849891
TI  - MicroRNAs as a target for novel antipsychotics: a systematic review of an
      emerging field.
AB  - The psychotic disorders of schizophrenia and bipolar affective disorder are among
      the most disabling of all medical conditions. Current drugs used to treat
      psychosis largely target monoamine receptors. Here we explore the possibility of
      developing new antipsychotics by targeting specific microRNAs (miRNAs). These are
      single-stranded RNA molecules, 21-23 nt in length that are not translated into
      proteins and function as regulatory molecules. A keyword search was performed
      using Medline, the ISI Web of Knowledge and Scopus for papers published up to
      June 2009. The search shows that to date studies of miRNAs have been far more
      abundant in schizophrenia than in bipolar affective disorder and the view that
      non-protein-coding genes have an important regulatory role with implications for
      the genetic liability to psychosis is gaining greater acceptance. The most
      promising miRNAs so far identified include miR-181, miR-346 and miR-195 in
      schizophrenia and miR-34a and miR-144 in bipolar disorder. It has been argued
      that miR-219 may be involved in both disorders. miRNAs offer an exciting
      potential for developing new antipsychotics, although research in the field is at
      an early stage. It will require a considerable advance in smart technologies to
      deliver either mimics or antagomirs to the appropriate site of action, but the
      development of selective small conventional molecules may negate this
      requirement.

PMID- 19849893
TI  - Does time reduce resistance to out-group critics? An investigation of the
      persistence of the intergroup sensitivity effect over time.
AB  - Group-directed criticism typically arouses greater defensiveness when it stems
      from an out-group member as opposed to an in-group member (the intergroup
      sensitivity effect). In light of work on the sleeper effect, the current research
      examines whether this defensiveness persists over time. Students received
      criticism of their faculty area from either a member of the same faculty area (in
      group condition), or a member of a different faculty area (out-group condition),
      or they received no criticism (control condition). Despite relatively poor recall
      of the content of the criticism, the intergroup sensitivity effect (ISE) found
      immediately after presentation of the criticism had not significantly decreased 3
      4 weeks later. However, the heightened intergroup bias found immediately after
      the out-group criticism did dissipate with time. Implications of these results
      for those who wish to initiate social change as outsiders are discussed.

PMID- 19849894
TI  - The effectiveness of routinely delivered cognitive behavioural therapy for
      obsessive-compulsive disorder: a benchmarking study.
AB  - OBJECTIVES: There is often difficulty in generalizing the results of randomized
      controlled trials (RCTs) to routine clinical practice given the rigid design
      features of such studies. The purpose of this study is to describe the
      effectiveness of routinely delivered, formulation-based cognitive behavioural
      therapy (CBT) within a publicly funded clinic for adults with obsessive
      compulsive disorder (OCD) and offer a comparison against the outcomes achieved in
      efficacy studies for the same population. METHOD: Practice-based prospective
      study. Routine data collected from a National Health Service out-patient clinic
      for adult clients with OCD is benchmarked against the findings of RCTs. The
      comparison RCTs were identified using a systematic review methodology. RESULTS:
      The mean (95% confidence interval) change in Yale-Brown Obsessive Compulsive
      Scale score pre- to post-therapy in the Sheffield clinic was 10.2 (7.1 - 13.3),
      which compares well with changes of 11.4 (10.5 - 12.2) for exposure and response
      prevention trials, 12.9 (11.2 - 14.7) for cognitive therapy trials, and 10.6 (8.5
      - 12.8) for CBT trials. The Sheffield results fell within the benchmarks derived
      from the included RCTs. CONCLUSION: These results indicate that CBT for adults
      with OCD delivered outside the constraints of a clinical trial is equivalently
      effective but that this conclusion should be tested further on a larger group of
      patients.

PMID- 19849895
TI  - Intravenous administration of 99mTc-HMPAO-labeled human mesenchymal stem cells
      after stroke: in vivo imaging and biodistribution.
AB  - Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after
      stroke. To deliver these cells, an IV injection appears safer than a local graft.
      We aimed to assess the whole-body biodistribution of IV-injected (99m)Tc-HMPAO
      labeled hMSC in normal rats (n = 9) and following a right middle cerebral artery
      occlusion (MCAo, n = 9). Whole-body nuclear imaging, isolated organ counting (at
      2 and 20 h after injection) and histology were performed. A higher activity was
      observed in the right damaged hemisphere of the MCAo group [6.5 +/- 0.9 x 10(-3)
      % of injected dose (ID)/g] than in the control group (3.6 +/- 1.2 x 10(-3)
      %ID/g), 20 h after injection. In MCAo rats, right hemisphere activity was higher
      than that observed in the contralateral hemisphere at 2 h after injection (11.6
      +/- 2.8 vs. 9.8 +/- 1.7 x 10(-3) %ID/g). Following an initial hMSC lung
      accumulation, there was a decrease in pulmonary activity from 2 to 20 h after
      injection in both groups. The spleen was the only organ in which activity
      increased between 2 and 20 h. The presence of hMSC was documented in the spleen,
      liver, lung, and brain following histology. IV-injected hMSC are transiently
      trapped in the lungs, can be sequestered in the spleen, and are predominantly
      eliminated by kidneys. After 20 h, more hMSC are found in the ischemic lesion
      than into the undamaged cerebral tissue. IV delivery of hMSC could be the initial
      route for a clinical trial of tolerance.

PMID- 19849896
TI  - Learning and disasters.

PMID- 19849897
TI  - Servants and leaders.

PMID- 19849898
TI  - Developing competences for learning in the age of the internet.

PMID- 19849899
TI  - Pandemic flu: putting plans into practice.

PMID- 19849900
TI  - Disaster planning: using an 'evolving scenario' approach for pandemic influenza
      with primary care doctors in training.
AB  - This project adopted an 'evolving scenario' approach of an influenza pandemic to
      enhance factual and attitudinal learning in general practice registrars. The one
      day session, held before the current outbreak, was based around a sequence of
      four video clips that portrayed the development and evolution of pandemic
      influenza through news flashes and pieces to camera. A short factual presentation
      was included. Small group discussions with plenary feedback followed each of
      these. Registrars were encouraged to consider their own feelings, what they
      needed as professional support at each stage, and what professional and personal
      issues a pandemic produced. A course structured in this way allowed participants
      at a training level to identify the major issues and consequences of an influenza
      pandemic. It was recognised that constructive preparation and planning for
      business continuity were possible. However, family illness and social
      consequences were recognised as causing a dissonance with professional practice
      that needs open debate.

PMID- 19849901
TI  - Preventing burnout among general practitioners: is there a possible route?
AB  - Stress and burnout among general practitioners (GPs) is a serious problem. Some
      authors suggest supervision groups or Balint groups as a means of preventing
      burnout and others address how to treat the condition. This paper reports a case
      study of a supervision group for Danish GPs which, as well as training reflective
      practice, focuses specifically on the prevention of burnout. The concept of
      compassion fatigue is extended to cover the circumstances reported by some
      practitioners in supervision.

PMID- 19849902
TI  - A conceptual description of potential scenarios of e-mentoring in GP specialist
      training.
AB  - The usefulness of face-to-face mentoring has been recognised in general practice
      for some time. E-learning is increasingly seen as an innovative way of supporting
      GPs in their continuing professional development. The fusion of e-learning and
      mentoring into e-mentoring is explored by a review of the literature and three
      potential GP specialist training scenarios are discussed. E-mentoring is
      effective, enhances face-to-face interaction with colleagues and should be driven
      by learning needs and educational principles.

PMID- 19849903
TI  - Questionnaire for quality management of general practice specialist training.

PMID- 19849904
TI  - Patients' attitudes to general practice registrars: a review of the literature.
AB  - With the population ageing, it is imperative for training practices to provide
      general practice registrars (GPRs) with sound experience in managing the health
      problems of older persons, especially chronic conditions. However, it is reported
      that a significant proportion of these patients will be resistant to consulting
      registrars, with concerns regarding disruption of continuity of care being a
      significant factor. The challenge for training practices is to identify
      approaches to engage registrars in the management of older patients whilst
      maintaining patient satisfaction. This paper presents a review of the literature
      on patient attitudes to GPRs to better understand the nature and magnitude of the
      challenge, and to identify important research gaps. Major electronic medical
      literature databases were searched for relevant articles using search terms
      including general practice, registrar, doctor-patient relationship, patient
      attitudes and elderly, for the period from January 1980 to March 2009. The
      studies were analysed by methodology, content and theme. A total of 15 studies
      were identified that directly addressed patients' attitudes to GPRs. Whilst there
      appeared to be an overall high acceptance of registrars by patients, increasing
      patient age was associated with more negative attitudes towards registrars,
      reduced trust and decreased satisfaction with communication. Presentations for
      chronic or emotional problems were associated with reduced willingness to consult
      registrars. Patients generally appreciated an ongoing involvement with their
      usual GP. These findings have implications for training practices and research
      directions. Demonstrating continuity of care through shared chronic disease
      management between supervisors and registrars is a possible model that meets
      registrars' training and patients' continuity needs. There is a need for quality
      research on the type and magnitude of problems affecting GPR encounters with
      older patients and, based on results from these studies, to create and assess
      models of registrar training involving older patients, that meet patients' needs
      for continuity of care.

PMID- 19849905
TI  - The application process for general practitioner trainers in United Kingdom
      deaneries: similarities and differences.
AB  - A survey was undertaken of the application and reapplication forms used by all
      the UK deaneries for general practice (GP) specialty training. The aim of the
      survey was to identify similarities and differences between deaneries in terms of
      the content and nature of the information requested, and the relationship of that
      information to the Postgraduate Medical Education and Training Board's (PMETB)
      Quality Assurance Framework (QAF). The details requested on the application forms
      were compared to the guidance set out in Generic Standards for Training, in order
      to see if they reflected the areas and standards required by the PMETB for the
      quality assurance of medical education and training. Although many similar areas
      of information were requested in the application process, great variation was
      found across some items which were not attributable to regional or contextual
      differences. The survey also found that the majority of domains of Generic
      Standards for Training are not well covered in the paper application process.
      Although deaneries may view their application processes for trainer approval as
      robust, this paper makes a number of recommendations and argues for the
      development of a standardised form for the appointment of general practice
      specialty training (GPST) trainers across the UK, based upon the PMETB QAF.

PMID- 19849906
TI  - Reflective online learning resource on functional symptoms: feedback on
      effectiveness.

PMID- 19849907
TI  - Do GPs' learning choices reflect their learning needs?

PMID- 19849908
TI  - Diversity: what is behind the CSA failure rates?

PMID- 19849909
TI  - How to ... Use questioning to enhance learning.

PMID- 19849910
TI  - Changes to training for general practice: still room for medical students?

PMID- 19849911
TI  - Oral contraceptives and venous thromboembolism: old questions revisited.

PMID- 19849912
TI  - Pandemic flu: implications for sexual and reproductive health services.

PMID- 19849913
TI  - EllaOne: a second-generation emergency contraceptive?

PMID- 19849914
TI  - How can we help people to choose a method of contraception? The case for
      contraceptive decision aids.

PMID- 19849915
TI  - Area disadvantage, socioeconomic position and women's contraception use: a
      multilevel study in the UK.
AB  - BACKGROUND AND METHODOLOGY: This study aimed to investigate associations between
      area-level socioeconomic disadvantage (central heating, car ownership and
      residents in professional occupations), individual-level socioeconomic position
      (social class and educational qualifications) and contraception use in the UK for
      the period 1990-1991. Multilevel logistic regression analysis was conducted on
      cross-sectional data from the National Survey of Attitudes and Lifestyles of 9793
      women, 16-59 years of age, residing in 646 postcode districts throughout the UK.
      RESULTS: Women with lower levels of formal education were less likely to use
      contraception than women with higher education [odds ratio (OR) 0.50, 95% CI 0.44
      0.57]. Women in the middle and low social class groups were less likely to use
      contraception than women in the higher social class group (OR 0.84, 95% CI 0.74
      0.97 and OR 0.66, 95% CI 0.56-0.79, respectively). The association between social
      class and contraception use varied significantly across postcode districts (p <
      0.001). The contraception use of women in the lowest social class group varied
      the most geographically. Women in the lowest quintiles of disadvantage were less
      likely to use contraception than women in the most advantaged quintiles according
      to all three measures, namely central heating (OR 0.76, 95% CI 0.61-0.94), car
      ownership (OR 0.67, 95% CI 0.53-0.84) and residents in professional occupations
      (OR 0.75, 95% CI 0.61-0.93). DISCUSSION AND CONCLUSION: Although more information
      is needed to understand how area and individual socioeconomic characteristics are
      associated with contraceptive use, this study suggests that policy on
      contraceptive use needs to be extended beyond individually targeted approaches
      and needs to take into account socioeconomic determinants of contraceptive use.

PMID- 19849916
TI  - Effect of self-triage on waiting times at a walk-in sexual health clinic.
AB  - BACKGROUND AND METHODOLOGY: Lengthy waiting times can be a major problem in walk
      in sexual health clinics. They are stressful for both patients and staff and may
      lead to clients with significant health issues leaving the department before
      being seen by a clinician. A self-triage system may help reduce waiting times and
      duplication of work, improve patient pathways and decrease wasted visits. This
      paper describes implementation of a self-triage system in two busy sexual and
      reproductive health clinics. Patients were asked to complete a self-assessment
      form on registration to determine the reason for attendance. This then enabled
      patients to be directed to the most appropriate specialist or clinical service.
      The benefits of this approach were determined by measuring patient waiting times,
      reduction in unnecessary specialist review together with patient acceptability as
      tested by a patient satisfaction survey. The ease of comprehension of the triage
      form was also assessed by an independent readers' panel. RESULTS: A total of 193
      patients were recruited over a 4-month period from November 2004 to February
      2005. Patients from the November and December clinics were assigned to the
      'traditional treatment' arm, with patients at subsequent clinics being assigned
      to the 'self-triage' system. Waiting times were collected by the receptionist and
      clinic staff. Ninety six patients followed the traditional route, 97 the new self
      triage system. Sixty-nine (35.8%) patients completed the satisfaction survey. The
      self-triage system significantly reduced waiting time from 40 (22, 60) to 23 (10,
      40) minutes [results expressed as median (interquartile range)]. There was a non
      significant reduction in the proportion of patients seeing two clinicians from
      21% to 13% (p = 0.17). Satisfaction levels were not significantly altered (95%
      compared to 97% satisfied, p = 0.64). The readers' panel found the triage form
      both easy to understand and to complete. CONCLUSIONS: Self-triage can effectively
      reduce clinic waiting times and allow better organisation of resources. Urgent
      cases can be prioritised. This process appears to be acceptable to and
      understandable by patients.

PMID- 19849917
TI  - Women's preferences for method of abortion and management of miscarriage.
AB  - BACKGROUND AND METHODOLOGY: There is growing interest in the UK towards
      increasing treatment options for women undergoing abortion and miscarriage. Such
      options include home medical treatment and surgery under local anaesthesia (LA).
      This study aimed to gauge views of women undergoing abortion and treatment for
      miscarriage at the Royal Infirmary Edinburgh towards medical treatment at home,
      and surgery under LA, to determine whether new services should be developed. The
      study consisted of a self-administered anonymous questionnaire. RESULTS: A total
      of 148 questionnaires were completed by women undergoing a medical abortion (n =
      97; 66%), surgical abortion (n = 30; 20%) or surgical management of miscarriage
      (n = 21; 14%). Women having an abortion expressed a future preference for medical
      abortion in hospital (n = 64; 52%) at home (n = 31; 25%) or by surgery under
      general anaesthesia (GA) (n = 20; 17%) or LA (n = 7; 6%). Women having a
      miscarriage expressed a future preference for surgery under GA (n = 7; 35%), LA
      (n = 6; 30%) or medical management at home (n = 4; 20%) or in hospital (n = 3;
      15%). CONCLUSIONS: This study shows that medical abortion at home is a
      potentially popular choice for women having an abortion, with surgical abortion
      under LA less so. Both home medical management and surgery under LA would appear
      to be welcome service developments for women needing treatment for a miscarriage.

PMID- 19849918
TI  - Aspects of herpes simplex virus: a clinical review.

PMID- 19849921
TI  - Unscheduled bleeding in combined oral contraceptive users: focus on extended
      cycle and continuous-use regimens.
AB  - Combined oral contraceptives (COCs) are highly effective when correctly used but
      unscheduled bleeding, which occurs fairly commonly during the early months, is
      disruptive for many women. The mechanisms underlying this bleeding are not fully
      understood. Several studies have shown that extended-cycle or continuous-use COCs
      are typically associated with higher initial rates of unscheduled bleeding than
      are conventional 21-day cyclical COCs. Some medicines, herbal supplements and
      smoking may increase unscheduled bleeding by interfering with estrogen
      metabolism. The most common cause of unscheduled bleeding is non-adherence to a
      prescribed COC regimen. Compliance can be improved by appropriate counselling of
      women about the possibility of unscheduled bleeding and the importance of
      adherence to the pill regimen. If abnormal bleeding persists beyond 3-4 months
      and causes such as incorrect usage can be ruled out, other causes should be
      considered.

PMID- 19849922
TI  - Integrated sexual health: a better way of working?

PMID- 19849923
TI  - The move to integrated contraception and sexual health services: have we
      forgotten family 'planning'?

PMID- 19849924
TI  - Pollyanna or Fright Night? Over-optimism versus negativity in the sexual health
      setting.

PMID- 19849925
TI  - The politics of contraception: policies lost and regained.

PMID- 19849926
TI  - "Follow me": the life of courtesans and virgins in the classical world.

PMID- 19849927
TI  - Taking the service to the young people: a study and analysis of a clinic
      specifically set up for HPV vaccination provision.

PMID- 19849929
TI  - Pregnancy at time of change of Implanon implant.

PMID- 19849930
TI  - Implant location technique.

PMID- 19849931
TI  - Acceptance of ligation and resection of tubes for contraception in Sri Lanka.

PMID- 19849933
TI  - Localised lipoatrophy at the site of Implanon insertion.

PMID- 19849934
TI  - [Biologic features of 688 cases of childhood acute leukemia-a single centre
      retrospective study].
AB  - OBJECTIVE: To investigate the biologic features of childhood acute leukemia in
      the northern region of China through a small cohort study in a single center.
      METHODS: The medical records of 688 children with acute leukemia (age< or =15
      years) who were initially diagnosed at Blood Disease Hospital of Chinese Academy
      of Medical Sciences from October 2003 to June 2006 were retrospectively studied.
      RESULTS: Four hundred children were diagnosed as acute lymphoblastic leukemia
      (ALL), with a peak incidence at ages of 1-4 years. Two hundred and eighteen
      children were classified into B-cell ALL, and 34 into T-cell ALL. In the 154
      patients with cytogenetic data, high hyperdiploidy was presented in 13.0% of
      patients, low hyperdiploidy in 3.9%, pseudodiploidy in 5.2%, and hypodiploidy in
      5.8%. E2A-PBX1 fusion gene was expressed in 3.9% of children with B-cell ALL. Two
      hundred and twenty-two children were diagnosed as acute myeloid leukemia (AML),
      with a peak incidence at ages of 10-15 years. AML-M2 was the most common subtype.
      Acute hybrid leukemia (AHL) was confirmed in 24 children (4.2%), with a median
      age of 9 years. Seventy-four percent of the children with (AHL) had mainly CD13
      and CD33 expression in myeloid antigen integral. CONCLUSIONS: There are
      differences in the biologic features of childhood acute leukemia between the
      northern region of China and other regions and races, which suggests that there
      might be differences in the pathogenesis of childhood acute leukemia in different
      environmental exposures.

PMID- 19849935
TI  - [Levels of Toll-like receptors-2,-4 on platelets in children with idiopathic
      thrombocytopenic purpura].
AB  - OBJECTIVE: To study the changes and significance of Toll-like receptor-2 (TLR2)
      and Toll-like receptor-4 (TLR4) on platelets, CD86 on lymphocytes and
      concentrations of IL-2, IFN-gamma, IL-4 and IL-10 in serum in children with
      idiopathic thrombocytopenic purpura (ITP). METHODS: Peripheral blood samples were
      collected from 24 children with acute idiopathic thrombocytopenic purpura (AITP),
      21 children with chronic idiopathic thrombocytopenic purpura (CITP) and 20 normal
      children (control group). Expression of TLR2 and TLR4 on platelets and CD86 on
      lymphocytes were detected by flow cytometry. Serum concentrations of IL-2, IL-4,
      IL-10 and IFN-gamma were measured using ABC-ELISA. RESULTS: The expression of
      CD41+TLR2+ and CD61+TLR4+ in the AITP and the CITP groups were significantly
      lower than those in the control group (p<0.01). The AITP group had lower
      expression of CD41+TLR2+ and CD61+TLR4+ than the CITP group (p<0.01). The
      expression of CD86+ in the AITP and the CITP groups was significantly higher than
      that in the control group (p<0.01). The serum concentrations of IL-2, IL-4, IL-10
      and IFN-gamma in the AITP and the CITP groups were significantly higher than
      those in the control group (p<0.05). There was a positive correlation between
      CD41+TLR2+ and CD61+TLR4+ expression. CD41+TLR2+ and CD61+TLR4+ expression were
      negatively correlated with CD86+ expression and serum concentrations of IL-2, IL
      4 and IL-10. CONCLUSIONS: The detections of TLR2 and TLR4 on platelets, CD86 on
      lymphocytes and serum concentrations of IL-2, IFN-gamma, IL-4 and IL-10 are of
      great value in understanding the pathogenesis and predicting types of ITP in
      children.

PMID- 19849936
TI  - [Changes of serum leptin and vascular endothelial growth factor in children with
      congenital heart disease].
AB  - OBJECTIVE: To study the changes of serum leptin (LEP) and vascular endothelial
      growth factor (VEGF) in children with congenital heart disease(CHD) and their
      roles in CHD. METHODS: Forty-eight children with acyanotic CHD (ACHD group), 20
      age-matched children with cyanotic CHD (CCHD group) and 20 healthy children
      (control group) were enrolled. The ACHD group was subdivided into two groups with
      (n=20) or without concurrent heart failure (n=28). Serum LEP, VEGF, total protein
      and albumin levels and body mass index (BMI) were measured. RESULTS: Serum total
      protein and albumin levels were not apparently different in all CHD children from
      healthy controls, but there was a significant difference in the BMI between them
      (p<0.01). Serum LEP and VEGF levels and the ratio of LEP/BMI in all CHD children
      were significantly higher than those in healthy controls (p<0.01). Compared with
      the ACHD group without heart failure, the serum LEP and VEGF levels and the ratio
      of LEP/BMI in the CCHD and the ACHD with heart failure groups increased
      significantly (p<0.01). In the ACHD group, serum LEP level was positively
      correlated with BMI (p<0.01). In the CCHD group, there were positive correlations
      between serum LEP level and serum VEGF level (p<0.01) and between hemoglobin
      concentration and serum VEGF level (p<0.01). Arterial oxygen saturation was
      negatively correlated with serum VEGF (p<0.01) and LEP levels (p<0.01) in the
      CCHD group. CONCLUSIONS: Both VEGF and LEP play roles in the pathophisiological
      process of CHD. VEGF and LEP are associated with the development of heart failure
      in children with ACHD.

PMID- 19849937
TI  - [Evaluation of cardiac function in fetuses from pregnant women with abnormal
      blood glucose levels by brain natriuretic peptide in umbilical cord blood].
AB  - OBJECTIVE: To study the feasibility of umbilical cord brain natriuretic peptide
      (BNP) level measurement for the evaluation of perinatal cardiac function in
      fetuses from pregnant women with abnormal blood glucose levels and the influence
      of abnormal blood glucose on fetal cardiac function. METHODS: Twenty-four mothers
      with gestational diabetes mellitus (n=18) or gestational impaired glucose
      tolerance (n=6) (diabetic group) were classified into two subgroups according to
      blood glucose level before delivery: good (n=17) and poor (n=7) glucose control.
      They underwent fetal echocardiography in their late pregnant periods and fetal
      cardiac sizes and function were measured. Twenty-five normal pregnant mothers
      served as the control group. Umbilical cord blood BNP concentrations were
      measured at delivery. RESULTS: The umbilical cord blood BNP concentrations in the
      diabetic group were significantly higher than in the control group(114.0+/-39.0
      pg/mL vs 80.6+/-13.7 pg/mL; p<0.01). The poor glucose control subgroup
      demonstrated higher umbilical cord blood BNP concentrations than the good glucose
      control subgroup (142.1+/-44.1 pg/mL vs 102.4+/-31.2 pg/mL; p<0.01). No
      difference was found between the gestational diabetes mellitus and the impaired
      glucose tolerance groups. The BNP concentration was positively correlated to the
      thicknesses of fetal left ventricular walls and the peak velocities of mitral A
      wave (r=0.715, 0.491 respectively, p<0.05), and negatively correlated to the
      mitral E/A ratio (r=-0.507, p<0.05). CONCLUSIONS: The fetuses of pregnant women
      with abnormal blood glucose levels have an increased BNP level in umbilical cord
      blood. Umbilical cord BNP level is related to maternal blood glucose control and
      the changes in fetal cardiac function. It may reflex the latent impairments of
      fetal cardiac function. A good glucose control may decrease the impact of
      abnormal maternal blood glucose on fetal hearts.

PMID- 19849938
TI  - [Persistent hyperinsulinemic hypoglycemia of infancy: clinical analysis of 12
      cases].
AB  - OBJECTIVE: To study the diagnosis and treatment of persistent hyperinsulinemic
      hypoglycemia of infancy. METHODS: The clinical data of 12 infants with persistent
      hyperinsulinemic hypoglycemia were retrospectively reviewed. RESULTS: Convulsion,
      cyanosis, lethargy, refusing milk sucking, irritability and sweating were common
      symptoms. The laboratory findings displayed persistent hypoglycemia and
      hyperinsulinism in all of the 12 infants. The glucagon test showed positive and
      no urine ketones were detected in all of the 12 infants. Seven infants were
      treated with oral diazoxide (5-15 mg/kg daily) and 4 infants showed effective to
      the therapy. One patient was given subtotal pancreatectomy and the blood glucose
      level was restored to normal after operation. Of the 12 infants, 6 presented
      psychomotor retardation in a follow-up of 2 months to 67 months, 3 had loss to
      follow-up and 3 were still in a follow-up. CONCLUSIONS: The measurement of blood
      glucose, blood insulin and urinary ketons is helpful in the diagnosis of
      persistent hyperinsulinemic hypoglycemia of infancy. Diazoxide therapy is
      effective in some of patients.

PMID- 19849939
TI  - [Hypersensitive C-reactive protein test in the diagnosis of early-onset infection
      in premature infants].
AB  - OBJECTIVE: To evaluate the clinical value of serum hypersensitive C-reactive
      protein (hsCRP) test in early diagnosis of early-onset infection in premature
      infants. METHODS: Thirty-five premature infants with early-onset infection, 50
      premature infants with non-infectious diseases and 40 healthy premature infants 3
      hrs after birth were enrolled. Serum hsCRP levels were measured by particle
      enhanced immunoturbidimetric assay. Diagnostic test of hsCRP was performed.
      RESULTS: Serum hsCRP levels shown as medium and inter-quartile ranges (M, Q75-25)
      were 2.19 and 4.96 mg/L respectively in the infection group, 0.41 and 0.61 mg/L
      respectively in the non-infectious disease group, and 0.24 and 0.28 mg/L
      respectively in the healthy group. Serum hsCRP levels in the infection group were
      significantly higher than those in the non-infectious disease and the healthy
      groups. When serum hsCRP test was used for the diagnosis of early-onset
      infection, the area under the ROC curve was 0.84, 95% confidence interval was
      0.76-0.93, the diagnostic sensitivity and specificity were 74% and 86%
      respectively, and the positive and negative predictive values were 37% and 97%
      respectively. ConclusionsSerum hsCRP test is valuable in early diagnosis of early
      onset infection in premature infants, but it can not serve as an independent
      diagnostic marker.

PMID- 19849940
TI  - [Hair root fragile X mental retardation protein assay for the diagnosis of
      fragile X syndrome].
AB  - OBJECTIVE: Fragile X syndrome (FXS) may be identified by many methods, such as
      PCR assay and Southern blot. However, each method has its limits or shortcomings.
      This study explored the reliability of the rapid, convenient and inexpensive hair
      root fragile X mental retardation protein (FMRP ) assay in the identification of
      FXS. METHODS: FMRP in hair roots was determined by immunohistochemistry assay in
      80 healthy children, in 40 children with mental retardation of unknown etiology
      and in 12 family members in one pedigree of FXS. FXS was confirmed by 7-deza-dGTP
      PCR. RESULTS: There was a high expression of FMRP in hair roots (> or =80%) in
      healthy children. Two children were confirmed with FXS by 7-deza-dGTP PCR in 40
      children with mental retardation of unknown etiology. FMRP expression was 10% and
      zero respectively in the two children. The other 38 children had FMRP expression
      of more than 80%. FMRP was not expressed in the two cases of FXS from the
      pedigree of FXS. CONCLUSIONS: Inexpensive, rapid and convenient hair root FMRP
      assay is reliable for the diagnosis of FXS and may be widely applied for
      screening and diagnosing FXS in children with mental retardation.

PMID- 19849941
TI  - [Association of tumor necrosis factor-alpha-308G/A and interleukin-6-174G/C gene
      polymorphisms with the susceptibility of respiratory syncytial virus
      bronchiolitis].
AB  - OBJECTIVE: To study the association of tumor necrosis factor (TNF)-alpha-308G/A
      and interleukin (IL)-6-174G/C gene polymorphisms with the susceptibility of
      respiratory syncytial virus (RSV) bronchiolitis. METHODS: Polymerase chain
      reaction-restriction fragment length polymorphism ( PCR-RFLP) was used to
      identify the polymorphisms at position 308 of the TNF-alpha promoter and -174 of
      the IL-6 promoter in 150 children with RSV bronchiolitis and 120 healthy children
      (control group). RESULTS: The frequency of GG, GA and AA genotypes of TNF-alpha
      308 was 68.0%, 28.0% and 4.0% respectively in the RSV group, while that was
      80.8%, 19.2% and 0 respectively in the control group. There were significant
      differences in the genotype frequencies between the two groups (chi2=5.665,
      p<0.05). The frequency of G and A alleles in the RSV group was 82.0% and 18.0%
      respectively, while that was 90.4% and 9.6% respectively in the control group.
      The frequency of A allele in the RSV group was significantly higher than that in
      the control group (chi2=7.726, p<0.05). Compared to the children carrying G
      allele, the children with A allele demonstrated a 2.071-fold increased risk of
      RSV bronchiolitis (OR=2.071, p<0.05). Only GG genotype was detected at position 
      174 of IL-6 in both groups. CONCLUSIONS: TNF-alpha-308A is associated with the
      susceptibility of RSV bronchiolitis and it might be an important candidate gene
      for the development of RSV bronchiolits. IL-6-174G/C gene polymorphism is not
      found in children in Wenzhou area.

PMID- 19849942
TI  - [Detection of respiratory syncytial virus in children with respiratory tract
      infections by nucleic acid amplification fluorogenic quantitative assay].
AB  - OBJECTIVE: Nucleic acid amplification (PCR) fluorogenic quantitative assay is
      used for the diagnosis of respiratory syncytial virus (RSV) infection. This study
      was designed to explore the sensitivity of PCR fluorogenic quantitative assay for
      ascertaining respiratory RSV infection and RSV infection conditions by detecting
      the presence of RSV-RNA related sequences in children. METHODS: Bronchial and
      nasopharyngeal secretions specimens from 261 hospitalized children with
      respiratory tract infections from January 2007 to October 2008 were collected.
      Respiratory syncytial virus nucleic acid (RNA) in the specimens was measuredby
      PCR fluorogenic quantitative assay. Blood RSV-IgM was detected by enzyme linked
      immunosorbent assay (ELISA). The sensitivity for ascertaining respiratory RSV
      infection was compared between the two assays. RESULTS: The RSV-RNA positive rate
      ascertained by PCR fluorogenic quantitative assay (38.7%) was significantly
      higher than blood RSV-IgM positive rate (21.1%) (p<0.01). The RSV-RNA positive
      rate (43.6%) in children at ages of less than 6 months was significantly higher
      than that in children at ages of 1 to three years (32.1%) (p<0.01). The RSV-RNA
      positive rate in children with bronchiolitis (58.5%) was the highest, followed by
      bronchopneumonia (38.2%) and acute bronchitis (20.0%). CONCLUSIONS: The
      sensitivity of PCR fluorogenic quantitative assay for ascertaining respiratory
      RSV infection is higher. RSV is a major pathogen of lower respiratory tract
      infections in infants and young children. A higher rate of RSV infection is
      associated with a younger age. RSV infection is the most common in children with
      bronchiolitis.

PMID- 19849943
TI  - [Changes of CD4+CD25+ regulatory T cells, IL-10 and TGF-beta1 levels in
      peripheral blood in children with asthma].
AB  - OBJECTIVE: This study determined the changes of CD4+CD25+ regulatory T cells, IL
      10 and TGF-beta1 levels in peripheral blood in children with asthma in order to
      explore immunologic mechanism of asthma attacks. METHODS: Seventy-four children
      with asthma attacks, twenty-eight children with stable asthma and twenty healthy
      children were enrolled. The percentage of CD4+CD25+ regulatory T cells in CD4+ T
      cells in peripheral blood was detected by flow cytometry. Serum levels of IL-10
      and TGF-beta1 were measured using enzyme linked immunosorbent assay (ELISA).
      RESULTS: The percentage of CD4+CD25+ regulatory T cells and IL-10 levels in
      peripheral blood in the asthma attacks group were significantly lower than those
      in the stable asthma and the control groups (p<0.01) .The stable asthma group
      showed a similar percentage of CD4+CD25+ regulatory T cells and IL-10 levels to
      the control group. Compared with the stable asthma and the control groups, serum
      TGF-beta1 level in the asthma attacks group increased significantly (p<0.05). In
      the asthma attacks, the stable asthma, and the control groups, the percentage of
      CD4+CD25+ regulatory T cells in peripheral blood was not correlated to serum
      levels of IL-10 and TGF-beta1. CONCLUSIONS: The percentage of CD4+CD25+
      regulatory T cells in peripheral blood and serum IL-10 levels decrease and serum
      TGF-beta1 levels increases in children with asthma attacks, which results in a
      decreased immunosuppressive effect. This might contribute to one of the
      immunologic mechanisms of asthma attacks.

PMID- 19849944
TI  - [Intelligence level and structure in school age children with fetal growth
      restriction].
AB  - OBJECTIVE: To study the intelligence level and structure in school age children
      with fetal growth restriction (FGR). METHODS: The intelligence levels were tested
      by the Wechsler Children Scales of Intelligence (C-WISC) in 54 children with FGR
      and in 84 normal children. RESULTS: The full intelligence quotient (FIQ), verbal
      IQ (VIQ) and performance IQ (PIQ) in the FGR group were 105.9+/-10.3, 112.4+/
      11.2 and 97.1+/-10.6 respectively, and they all were in a normal range. But the
      PIQ was significantly lower than that in the control group (104.8+/-10.5;
      p<0.001), and the picture arrangement and the decipher subtest scores were
      significantly lower than those in the control group (p<0.01). The scores of
      perception/organization and memory/attention factors in the FGR group were 99.8+/
      11.1 and 116.3+/-14.4, respectively, which were inferior to those in the control
      group (104.6+/-11.5 and 113.4+/-14.5 respectively; p<0.05). CONCLUSIONS: The
      total intelligence level of children with FGR is normal, but there are imbalances
      in the intelligence structure and dysfunctions in performance ability related to
      right cerebral hemisphere. Performance trainings should be done from the infancy
      in children with FGR.

PMID- 19849945
TI  - [Developmental changes of acetabular cartilage complex: an experimental study of
      a straight-leg swaddle model of newborn rats].
AB  - OBJECTIVE: By establishing a model of straight-leg swaddle of newborn rats and
      observing the experimental animals'hips morphologically and pathologically, this
      study explored the changes of gross appearance of the acetabulum and the maturity
      of cartilage cells in the different regions of acetabular cartilage complex.
      METHODS: The legs and hips were fixed by adhesive tape for 10 days in the
      position of hip extension and adduction in 31 newborn Wistar rats (experimental
      group). The other 31 newborn rats without legs and hips treatment were used as
      the control group. After 10 days raising in the same condition, all the rats were
      sacrificed. The gross appearance, histological observations and VEGF and type X
      collagen immunohistochemistry were used for examining the acetabulum changes.
      RESULTS: A straight leg swaddle model of newborn rats was established
      successfully. In the experimental group the acetabulum became shallow and small
      and surrounded by more soft tissues. There were 49 dislocated hips (49/54) in the
      experimental group and 2 hips dislocated (2/60) in the control group (p<0.01).
      Fake acetabulum appeared in the experimental group. In the control group, the
      shape of the acetabulum was normol, and no fake acetabulum was found. The
      safranin O-fast green staining showed that the orange-red cartilage in the
      experimental group was wider than the control group. Immunohistochemistry
      observations showed VEGF and type X collagen immunoreactivities in the
      hypertrophic layer of the acetabular cartilage complex in the experimental group
      were lower than those in the control group. The percentages of VEGF positive and
      type X collagen positive cells in the iliac hypertrophic layer of the acetabular
      articular cartilage were significantly higher than those in the ischiadic ramus
      and the pubic branch in the experimental group. CONCLUSIONS: VEGF and type X
      collagen immunoreactivities in acetabular cartilage cells decrease in a straight
      leg swaddle model of newborn rats. This suggests that this position might lead to
      dysmaturity of the acetabular cartilage cells and affect the development of the
      acetabulum.

PMID- 19849946
TI  - [Effects of ganglioside 1 and nerve growth factor on the proliferation of neural
      stem cells in vitro].
AB  - OBJECTIVE: To study the effects of ganglioside 1 (GM1) and nerve growth factor
      (NGF) on neural stem cells (NSCs) proliferation in vitro. METHODS: NSCs were
      isolated and cultured in vitro. NSCs were cultured in the medium containing
      epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) or
      without the two agents. Different concentrations of GM1 and NGF were added into
      the two different medium. MTT and cell ball counting methods were used to
      ascertain the proliferation of NSCs. Immunohistochemical technology was used to
      observe the effect of GM1 and NGF on the proliferation of NSCs. RESULTS: High
      concentrations of GM1 (100 ng/L and 200 ng/L) promoted significantly the
      proliferation of NSCs in the medium containing EGF and bFGF (p<0.05). In the
      differentiation medium containing serum but no EGF and bFGF, NSCs proliferation
      increased with increasing concentration of GM1; the proportion of neurons and
      gliacytes increased with increasing concentration of NGF. CONCLUSIONS: High
      concentration of GM1 can promote NSCs proliferation and NGF can promote NSCs
      differentiation.

PMID- 19849947
TI  - [Effects of NYGGF4 gene over-expression on the insulin sensitivity and secretory
      function of adipocytes].
AB  - OBJECTIVE: To study the effect of a new obesity-related gene NYGGF4 on the
      insulin sensitivity and secretory function of adipocytes. METHODS: 3T3-L1
      preadipocytes transfected with either an empty expression vector (pcDNA3.1;
      control group) or an NYGGF4 expression vector (NYGGF4-pcDNA3.1) were cultured in
      vitro and differentiated into the matured adipocytes with the standard insulin
      plus dexamethasone plus 3-isobutyl-methylxanthine (MDI) induction cocktail. 2
      deoxy-D-[3H] glucose uptake was determined by liquid scintillation counting.
      Western blot was performed to detect the protein content and translocation of
      glucose transporter 4 (GLUT4). The supernatant concentrations of TNF-alpha, IL-6,
      adiponectin and resistin were measured using ELISA. RESULTS: NYGGF4 over
      expression in 3T3-L1 adipocytes reduced insulin-stimulated glucose uptake. NYGGF4
      over-expression impaired insulin-stimulated GLUT4 translocation without affecting
      the total protein content of GLUT4. The concentrations of TNF-alpha, IL-6,
      adiponectin and resistin in the culture medium of 3T3-L1 transfected with NYGGF4
      were not significantly different from those in the control group. CONCLUSIONS:
      NYGGF4 over-expression impairs the insulin sensitivity of 3T3-L1 adipocytes
      through decreasing GLUT4 translocation and had no effects on the secretory
      function of adipocytes.

PMID- 19849948
TI  - [Roles of platelet and its regulating factors in immune vasculitis in young
      rabbits].
AB  - OBJECTIVE: To study the roles of platelet (PLT) and its regulating factors,
      megakaryocyte, thrombopoietin (TPO) and transforming growth factor beta1 (TGF
      beta1), in immune vasculitis in young rabbits. METHODS: An experimental model of
      Kawasaki disease (KD) of weanling rabbits was reproduced by bovine serum. PLT
      count, total number and differentiating count of megakaryocyte, and serum TPO and
      TGF-beta1 levels were measured 0, 4, 8, 12, 16, 20, 24 and 28 days after KD
      induction. Pathological analysis of coronary artery, liver, spleen, kidney and
      brain was performed 17 and 28 days after KD induction. RESULTS: In the KD group,
      PLT count, the total number of megakaryocyte, and the middle board megakaryocyte
      percentage increased 12, 16, 20, 24 and 28 days; serum TPO level increased 8, 12,
      16, 20, 24 and 28 days; serum TGF-beta1 level increased 16, 20, 24 and 28 days
      after KD induction compared with those in the normal control group (p<0.05). The
      pathological examinations of coronary artery, liver, spleen, kidney and brain
      showed severe inflammatory injuries of tiny arteries and small/medium-sized
      arteries 17 and 28 days after KD induction, respectively in the KD group. The
      aortas were showed as mild inflammatory injuries. CONCLUSIONS: PLT,
      megakaryocyte, TPO and TGF-beta1 participate in the pathogenesis of KD, and they
      may play an important role in the injuries of immune vasculitis. This suggests
      that they may serve as markers for the assessment of severity in KD.

PMID- 19849949
TI  - [A report of both mother and her newborn baby suffering from measles].

PMID- 19849950
TI  - [Tethered cord syndrome of thick filum terminale in children].

PMID- 19849951
TI  - [Eosinophilic cardiomyopathy in a child].

PMID- 19849952
TI  - [Callosal agenesis complicated by intracranial multiple lipoma in a newborn
      infant].

PMID- 19849953
TI  - [Successful treatment of meningitis caused by enterovirus 71 infection in a
      child].

PMID- 19849954
TI  - [Progress in the research on cell-free fetal DNA in maternal plasma].

PMID- 19849955
TI  - [Progress in the research on the role of mesangial remodeling in glomerualr
      diseases].

PMID- 19849956
TI  - [Role of cytokines in Henoch-Schonlein purpura nephritis].

PMID- 19849957
TI  - [Fascioliasis hepatica: a case report].

PMID- 19849958
TI  - Endovascular stents for abdominal aortic aneurysms: a systematic review and
      economic model.
AB  - OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of
      endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms
      (AAAs) in patients at varying levels of risk. DATA SOURCES: The following
      bibliographic databases were searched (2005-February 2007): BIOSIS Previews,
      CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ISI Proceedings,
      MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Science Citation Index
      and Zetoc Conferences. REVIEW METHODS: A systematic review of the clinical
      effectiveness of EVAR was performed using standard methods. Meta-analysis was
      employed to estimate a summary measure of treatment effect on relevant outcomes
      based on intention to treat analyses. A second systematic review was undertaken
      to identify existing cost-effectiveness analyses of EVAR compared with open
      surgery and non-surgical interventions. Two new decision models were developed to
      inform the review. RESULTS: Six RCTs were included in the clinical effectiveness
      review. Thirty-four studies evaluated the role of patients' baseline
      characteristics in predicting risks of particular outcomes after EVAR. The
      majority were based on data relating to devices in current use from the EUROSTAR
      registry. Compared with open repair EVAR reduces operative mortality (odds ratio
      0.35, 95% CI 0.19 to 0.63) and medium-term aneurysm-related mortality (hazard
      ratio 0.49, 95% CI 0.29 to 0.83) but offers no significant difference in all
      cause mortality. EVAR is associated with increased rates of complications and
      reinterventions, which are not offset by any increase in health-related quality
      of life. EVAR trial 2 comparing EVAR with non-surgical management in patients
      unfit for open repair found no differences in mortality between groups; however,
      substantial numbers of patients randomised to non-surgical management crossed
      over to receive surgical repair of their aneurysm. The cost-effectiveness
      systematic review identified six published decision models. Both models
      considered relevant for the decision in the UK concluded that EVAR was not cost
      effective on average compared with open repair at a threshold of 20,000 pounds
      per quality-adjusted life-year (QALY). Another model concluded that EVAR would be
      on average more cost-effective than no surgical intervention in unfit patients at
      this threshold. The Medtronic model concluded that EVAR was more cost-effective
      than open repair for fit patients at this threshold. The York economic
      evaluations found that EVAR is not cost-effective compared with open repair on
      average at a threshold of 30,000 pounds per QALY, with the results very sensitive
      to model assumptions and the baseline risk of operative mortality. Exploratory
      analysis to evaluate management options in patients unsuitable for open surgery
      suggested that the cost-effectiveness of EVAR may be sensitive to aneurysm size
      and patient's age at operation. Indicative modelling suggests that EVAR may be
      cost-effective for small aneurysms in some patient groups. Ongoing RCTs will
      provide further evidence relating to these patients. CONCLUSION: Open repair is
      more likely to be cost-effective than EVAR on average in patients considered fit
      for open surgery. EVAR is likely to be more cost-effective than open repair for a
      subgroup of patients at higher risk of operative mortality. These results are
      based on extrapolation of mid-term results of clinical trials. Evidence does not
      currently support EVAR for the treatment of ruptured aneurysms. Further follow-up
      of the existing UK trials should be undertaken and the relative costs of
      procedures and devices should be investigated further.

PMID- 19849959
TI  - Modified directly observed therapy to improve HIV treatment outcomes: little
      impact with potent, once-daily therapy in unselected antiretroviral-naive
      patients.

PMID- 19849960
TI  - Improving the self-report of HIV antiretroviral medication adherence: is the
      glass half full or half empty?
AB  - Self-reports are the most widely used method for measuring antiretroviral
      adherence. The association between self-reports and viral loads has been
      repeatedly demonstrated, but this association does not address how well self
      reports measure actual medication-taking behaviors. Understanding adherence self
      reports requires studying the science of memory and the reporting of behaviors.
      In the first section of this review, we discuss research in cognitive psychology
      that pertains to adherence self-reports, focusing primarily on studies that
      examine cognitive processes respondents use to answer survey questions. In the
      second section, we review recent articles examining the relationship between self
      reports and objective measures of adherence, highlighting the strength of
      associations and key methodologic issues. We conclude with key questions for
      future research and methodologic recommendations.

PMID- 19849961
TI  - Behavioral aspects of male circumcision for the prevention of HIV infection.
AB  - Male circumcision (MC) can prevent female-to-male HIV transmission and has the
      potential to significantly alter HIV epidemics. The ultimate impact of MC on HIV
      prevention will be determined, in part, by behavioral factors. In order to fully
      realize the protective benefits of MC, factors related to acceptability and
      sexual risk must be considered. Research shows that acceptability of MC among
      uncircumcised men is high, and suggests that free and safe circumcision may be
      taken up in places with high HIV prevalence. Perceptions of adverse effects of MC
      may, however, limit uptake. Furthermore, considerable risk reduction counseling
      provided by MC trials limits our ability to understand the impact MC may have on
      behavior. There is also no evidence that MC protects women with HIV-positive
      partners or that it offers protection during anal intercourse. Research is
      urgently needed to better understand and manage the behavioral implications of MC
      for HIV prevention.

PMID- 19849962
TI  - Pediatric adherence to HIV antiretroviral therapy.
AB  - More than 2 million children are infected with HIV globally. Pediatric
      antiretroviral therapy (ART) adherence is complex, and current levels are often
      suboptimal. As established treatment programs in developed settings struggle with
      chronic therapy and nascent treatment programs in resource-limited settings
      expand, the importance and challenges of good adherence to ART are becoming ever
      more clear. Adherence behavior is influenced by many factors, which may be
      categorized as characteristics of the child, the caregiver(s) and family, the
      regimen, and society and culture. Many of these influences complicate measurement
      of pediatric adherence, and there is no gold standard. This article provides a
      conceptual framework and evidence-based look at the factors influencing ART
      adherence in children and aims to identify areas for intervention for this
      vulnerable population in need.

PMID- 19849963
TI  - Providing antiretroviral care in conflict settings.
AB  - There has been an historic expectation that delivering combination antiretroviral
      therapy (cART) to populations affected by violent conflict is untenable due to
      population movement and separation of drug supplies. There is now emerging
      evidence that cART provision can be successful in these populations. Using
      examples from Medecins Sans Frontieres experience in a variety of African
      settings and also local nongovernmental organizations' experiences in northern
      Uganda, we examine novel approaches that have ensured retention in programs and
      adequate adherence. Emerging guidelines from United Nations bodies now support
      the expansion of cART in settings of conflict.

PMID- 19849964
TI  - Interactive voice response technology to measure HIV-related behavior.
AB  - Computerized telephone technology has garnered increasing interest as an
      assessment tool specifically for the collection of daily, near-contemporaneous
      self-reports of HIV risk behaviors. In this review, we discuss advantages and
      recent applications of interactive voice response technology (IVR) to HIV risk
      behavior research, including feasibility studies, assessment mode comparisons
      between IVR and alternative self-reporting methods, and unique findings derived
      from event-level data analyses illuminating risk factors for unprotected
      intercourse on within-person level. We also review reactivity effects of daily
      IVR self-reports and applications of IVR systems in risk behavior intervention
      research. We conclude that IVR is a feasible and highly promising tool for
      various research and health care applications that should be considered more
      frequently for use in HIV-risk populations.

PMID- 19849965
TI  - Home testing for HIV infection in resource-limited settings.
AB  - Among an estimated 33 million individuals who are infected with HIV worldwide,
      only 10% are aware of their status. HIV testing is the cornerstone to preventing
      further transmission and to caring for those infected, particularly as access to
      treatment improves in resource-limited settings. However, efforts to expand
      testing through facilities-based testing have not achieved adequate testing
      coverage, prompting efforts to reach more individuals through strategies such as
      home-based HIV testing. Home testing is showing promising early results in some
      high-prevalence, resource-limited settings. This article reviews the mechanisms
      and literature to date of this door-to-door approach.

PMID- 19849967
TI  - [Stroke: update on therapy].

PMID- 19849966
TI  - Food insecurity and HIV/AIDS: current knowledge, gaps, and research priorities.
AB  - Food insecurity and HIV/AIDS are intertwined in a vicious cycle that heightens
      vulnerability to, and worsens the severity of, each condition. We review current
      knowledge and research priorities regarding the impact of food insecurity on HIV
      transmission risk and clinical outcomes. Observational studies suggest that food
      insecurity is associated with increased HIV transmission risk behaviors and
      decreased access to HIV treatment and care. Among individuals receiving
      antiretroviral therapy (ART), food insecurity is associated with decreased ART
      adherence, reduced baseline CD4 cell count, incomplete virologic suppression, and
      decreased survival. Integration of food security interventions into HIV/AIDS
      treatment programs is essential to curtail the HIV/AIDS epidemic and improve
      health and quality of life among those infected. Longitudinal research applying
      validated measurement tools is needed to better understand the mechanisms through
      which food insecurity adversely impacts HIV transmission, treatment, and care.
      Research should compare the effectiveness of various food assistance and
      livelihood strategies.

PMID- 19849968
TI  - [Propagation of polyglutamine agregates in normal cells].

PMID- 19849969
TI  - [Chemotherapeutic treatment of gliomas increases the amount of cancer stem-like
      cells].

PMID- 19849970
TI  - [Cell movements break left/right symmetry in the chick embryo].

PMID- 19849971
TI  - [Asymetric growth in Drosophila stem cells is related to ribosomal biogenesis].

PMID- 19849972
TI  - [Neurodegenerative disorder in idiopathic REM sleep behaviour disorder].

PMID- 19849973
TI  - [ARF proteins: molecular switches controlling tumour proliferation and
      metastasis].

PMID- 19849974
TI  - [Mutations in TET2 in myeloid cancers].

PMID- 19849975
TI  - [Senescent-associated factors: pro- and anti-tumoral actions].

PMID- 19849976
TI  - [GNRH1 mutation in familial hypogonadotropic hypogonadism].

PMID- 19849977
TI  - [P53, ARF and P16: the last defence against reprogrammation].

PMID- 19849978
TI  - [Neurogenesis-dependent and independent effects of anti-depressant drugs].

PMID- 19849979
TI  - [Pluripotency: defining standards].

PMID- 19849980
TI  - [Birth of Mito and Tracker: mitochondrial gene replacement].

PMID- 19849982
TI  - [NR5A1 and ovarian failure].
AB  - Primary ovarian insufficiency (POI) is characterised by the arrest of normal
      ovarian function before the age of 40 years and affects 1 % of all women. POI
      shows familial inheritance suggesting a genetic contribution. NR5A1 is nuclear
      receptor that regulates the transcription of many genes involved in sexual
      developmental and reproduction. 18 NR5A1 mutations have been published associated
      with either anomalies of adrenal or testis development. We have identified NR5A1
      mutations associated with POI, including familial cases with affected 46,XY
      individuals. This demonstrates that NR5A1 plays an important role in ovarian
      development and function. However several questions remain. What is the incidence
      of NR5A1 mutations in POI? Is there a genotype/phenotype relationship? Are
      mutations associated with a progressive loss of reproductive function? Answering
      these questions will lead to a better understanding of ovarian function and
      dysfunction and could lead to new therapies for treating POI.

PMID- 19849983
TI  - [Na+ Transport in the lungs: differential impact of ENaC in the airways and
      alveoli].
AB  - Na+ transport by airway epithelial cells, in conjunction with Cl- secretion is
      crucial for maintaining an adequate level of airway surface liquid (ASL) for an
      effective mucociliary clearance by the ciliated airway epithelial cells. It is
      also an important mechanism for lung liquid absorption at birth and oedema
      absorption during an acute respiratory distress syndrome (ARDS). The epithelial
      Na+ channel (ENaC) is the channel mostly involved in this process. The
      consequences of an imbalance in ENaC activity in the airways and in the distal
      lung are different. Experimental over expression of ENaC in the airways leads to
      a decrease in mucociliary clearance and inflammation similar to cystic fibrosis
      and chronic bronchitis. However, bacterial and viral pathogens, as well as pro
      inflammatory cytokines present during lung infection downregulate ENaC expression
      and activity in airway and alveolar epithelial cells. ENaC downregulation by
      pathogens or inflammatory products could participate in the modulation of the
      severity of ARDS. Pharmacological strategies that modulate ENaC expression or
      activity could be important in the treatment of different lung diseases since it
      is actively involved in the lung innate defence mechanisms.

PMID- 19849984
TI  - [The role of molecular chaperones in the assembly of heterotrimeric G proteins].
AB  - Extracellular signals received by G protein-coupled receptors (GPCRs) are
      transduced into intracellular responses following the activation of
      heterotrimeric G proteins. As their names suggests, they are composed of three
      subunits, Galpha and Gbetagamma, the latter being effectively treated as a single
      entity. The Gbetagamma dimer is assembled with the aid of a number of molecular
      chaperones in a tightly regulated process. The folding of nascent Gbeta1 is
      favoured by cellular chaperones such as PhLP-1 and CCT and the ER-resident
      protein DRiP78 plays an important role in the stability of nascent Ggamma2
      subunits. However, much work remains to be done to completely understand the
      mechanisms underlying assembly of the heterotrimer.

PMID- 19849985
TI  - [Physical activity in preventing metabolic syndrome in children].
AB  - Metabolic syndrome defined as the joint manifestation on the same subject of
      several risk factors (at least 3 in the majority of definitions) within the
      following parameters : hypertriglyceridemia, hypertension, abdominal obesity, low
      concentration of HDL-Cholesterol (HDL-C), and high fasting blood glucose is
      increasingly reported in children, mainly in the presence of overweight/obesity.
      In fact, up to 50 % of overweight/obese children can be affected by this
      syndrome. Furthermore, the metabolic syndrome acquired during childhood has been
      shown to impact highly into adulthood including by its clinical complications
      such as type 2 diabetes or cardiovascular diseases. Among the practical
      preventive and therapeutic measures to be taken in children, physical activity
      appears to be an option of choice. This review indicates that physical activity
      programs based either on aerobic exercise, resistance training, or a combination
      of these 2 types of activity may promote insulin sensibility and weaken or
      suppress the metabolic syndrome of children. More interestingly, usual physical
      activity including free-living activities of an intensity equivalent to a brisk
      walking should be encouraged earlier among children for its positive influence on
      parameters involved in the metabolic syndrome.

PMID- 19849986
TI  - [Quantitative proteomics by SILAC: practicalities and perspectives for an
      evolving approach].
AB  - Mass spectrometry-based quantitative proteomics strategies are ideally adapted to
      the detection of global protein changes between different biological samples.
      Among these, SILAC (stable isotope labelling by amino acids in cell culture) has
      demonstrated a great potential. This method is extremely accurate and relatively
      easy to apply for the quantification of proteins extracted from cultured cells.
      SILAC involves cell culture either in regular culture media ("light" protein
      synthesis) or in media where amino acids have been replaced by their isotopically
      labelled counterparts ("heavy" protein synthesis). Cell populations to be
      compared can be mixed and treated as a single sample, which allows downstream
      sample preparation without the risk of introducing quantification errors. During
      mass spectrometry analysis, the relative protein abundance between biological
      samples can be calculated from the intensities of heavy and light peptides. As
      shown by numerous applications in biological and clinical studies, SILAC
      represents a promising method for the elucidation of cellular and physio
      pathological mechanisms and for the identification of disease biomarkers. The
      restriction of SILAC to the quantification of proteins from cultured cells has
      just been overcome with the description in a recent paper of a SILAC mouse, which
      will allow this technology to be applied to the differential study of -tissues
      and biological fluids from model animals.

PMID- 19849987
TI  - [Cellular microparticles, potential useful biomarkers in the identification of
      cerebrovascular accidents].
AB  - The clinical utility of biomarkers depends on their ability to identify high-risk
      individuals in order to establish preventive, diagnostic or therapeutic measures.
      Currently, no practical, rapid and sensitive test is available for the diagnosis
      of acute ischemic stroke. A number of soluble molecules have been identified that
      are merely associated to these cerebrovascular accidents. Despite this
      association not a single molecule has the characteristics of a true biomarker
      directly involved in the pathophysiology of ischemic stroke-none of them is organ
      specific and may therefore be elevated in the context of medical comorbidities.
      When explored as a combination of biomarkers, e.g. matrix metalloproteinase 9,
      brain natriuretic protein, D-dimer, protein S100B, the question still remains
      whether serial biomarker analysis provides additional prognostic information.
      Even S100B, a glial activation protein, has a low specificity for acute ischemic
      stroke because it may originate from extracranial sources. Current knowledge from
      the field of cell-derived microparticles suggests that these membrane fragments
      may represent reliable biomarkers as they are cell-specific and are released
      early in the pathophysiological cascade of a disease. These microparticles can be
      found not only in the cerebrospinal fluid but also in tears and circulating blood
      in case of blood-brain barrier dysfunction. They represent a new challenge in
      stroke diagnosis and management.

PMID- 19849988
TI  - [Cerebral ischaemia: tomorrow's therapeutic tracks].
AB  - Thrombolysis remains the main therapeutic strategy used in stroke, but with a
      limited use to only a part of stroke patients. A neuroprotective approach would
      be necessary with a double objective : (1) to serve as an add-on treatment with
      thrombolysis to improve safety and increase therapeutic window ; (2) to limit
      infarct area by delaying neuronal death. While numerous molecules failed in
      clinical trials in stroke, pharmacological development is on-going with
      pleiotropic drugs targeting both neuronal and vascular parts of neurovascular
      unit. Another approach targets the functional rehabilitation and the neurorepair
      using pharmacological ways or cell therapy.

PMID- 19849989
TI  - [Cerebral ischemia (2), How to neutralize the neurotoxic effects of tPA].

PMID- 19849990
TI  - [Impact of the environment on envenomation incidence and severity].
AB  - Envenomations constitute a serious public health problem in many developing
      countries. It is related to the hazards of the encounters of venomous animals and
      human explained by both the venomous animal behaviour and human activities.
      Severity depends on the toxicity or inoculated amount of the venom and, to a
      lesser extent, on the management of the envenomation. Man-induced alteration of
      the environment results in modifications of venomous animals populations both in
      proportion of species and abundance of specimens. Some species have a higher
      adaptation capacity and may grow up dramatically. In rural regions, plantations
      are at great risk of exposure to snakes whereas in suburban areas, scorpions may
      occur in high density. In some plantations or settlements, incidence may increase
      by two to ten folds. Local ecological and epidemiological studies allow taking
      measures to control the venomous animals, prevent the snakebites or scorpion
      stings and provide antivenoms and better management of the envenomations.

PMID- 19849991
TI  - [Japanese demography: paradoxes and perspectives].
AB  - Japan is one of the most densely-populated countries with a population estimated
      at 127.4 millions and an average density of 337 persons per square kilometer. But
      the National Institute of Population and Social Security Research is concerned:
      since 1950, the total fertility rate is declining and some pessimistic
      projections predict the japanese population extinction to 3000. During 2008,
      several reports, based on the major results of 2005 census, analyse population
      process components and establish projections based on alternative assumptions,
      looking for solutions limiting the population dependency ratio. On the site of
      the National Institute of Population and Social Security Research, the population
      pyramids are shown from 1930 to 2055. Recently, the French National Institute for
      demographic studies gave a comprehensive report on the Japanese demographic
      status, explaining the possible consequences for the country's demographic
      future.

PMID- 19849992
TI  - [Malaria in pregnancy: a therapeutic dilemma].

PMID- 19849993
TI  - [Kill to be born].

PMID- 19849994
TI  - [Chemoinformatics and virtual screening of molecules for therapeutic use].
AB  - Successful identification of new chemical entities with drug-like properties in
      pharmaceutical and academic research groups involves an early screen and the use
      of a large number of public and proprietary chemical libraries. Before applying
      high-throughput experimental screening approaches, virtual screening strategies
      have been put in place in order to sort and filter this massive amount of
      compounds and data available at these very early stages. Chemoinformatic tools
      have a crucial role in this selection process and enable therapeutic chemists to
      focus very early on promising candidates. Virtual screening has conventionally
      been based either on models of the target or the ligand (molecule), but today
      these models include biopharmaceutical filters addressing right from the start of
      the project the ADMET (absorption, distribution, metabolism, excretion, and
      toxicity) properties of the molecules. Above all, chemoinformatic tools help
      chemists understand better the chemical diversity they can work with, especially
      when comparing chemical libraries. This paper will focus on exemples of the day
      to-day use of chemoinformatics in screening programs. A large part will be
      dedicated to new tools (chemographic and pharmacographic approaches) being
      developed for the representation and analysis of chemical diversity, but also for
      combining chemical and biological information to expedite research programs.

PMID- 19849996
TI  - Intradermal influenza vaccine for older adults: a randomized controlled
      multicenter phase III study.
AB  - In a 3-year, randomized, controlled, open-label phase III trial enrolling 3707
      adults aged > or = 60 years we evaluated whether the immunogenicity of an
      intradermal trivalent inactivated seasonal influenza vaccine, containing 15
      microg of haemagglutinin per strain per 0.1 ml dose, is superior to that of a
      conventional intramuscular vaccine. Intradermal vaccine was given using an
      intradermal microinjection system. After the first vaccination, both vaccines
      satisfied the immunogenicity criteria for influenza vaccines for older adults set
      out in European regulatory guidelines, and geometric mean haemagglutination
      inhibition antibody titers and seroprotection rates were higher (statistically
      superior) with intradermal vaccination. Higher immune responses with intradermal
      vaccine were also observed after the 2nd and 3rd annual vaccinations. Both
      vaccines were well tolerated with similar systemic reactogenicity profiles. This
      intradermal influenza vaccine for older adults is a beneficial option for
      influenza protection, consistently enhancing antibody responses without
      compromising safety.

PMID- 19849995
TI  - Induction of mucosal and systemic antibody responses against the HIV coreceptor
      CCR5 upon intramuscular immunization and aerosol delivery of a virus-like
      particle based vaccine.
AB  - Virus-like particles (VLPs) can be exploited as platforms to increase the
      immunogenicity of poorly immunogenic antigens, including self-proteins. We have
      developed VLP-based vaccines that target two domains of the HIV coreceptor CCR5
      that are involved in HIV binding. These vaccines induce anti-CCR5 antibodies that
      bind to native CCR5 and inhibit SIV infection in vitro. Given the role of mucosal
      surfaces in HIV transmission and replication, we also asked whether an
      aerosolized, VLP-based pulmonary vaccine targeting CCR5 could induce a robust
      mucosal response in addition to a systemic response. In rats, both intramuscular
      and pulmonary immunization induced high-titer IgG and IgA against the vaccine in
      the serum, but only aerosol vaccination induced IgA antibodies at local mucosal
      sites. An intramuscular prime followed by an aerosol boost resulted in strong
      serum and mucosal antibody responses. These results show that VLP-based vaccines
      targeting CCR5 induce high-titer systemic antibodies, and can elicit both local
      and systemic mucosal response when administered via an aerosol. Vaccination
      against a self-molecule that is critically involved during HIV transmission and
      pathogenesis is an alternative to targeting the virus itself. More generally, our
      results provide a general method for inducing broad systemic and mucosal antibody
      responses using VLP-based immunogens.

PMID- 19849997
TI  - Determination of urinary adenosine using resonance light scattering of gold
      nanoparticles modified structure-switching aptamer.
AB  - A novel sensitive method has been developed for the detection of adenosine (AD)
      in human urine by using enhanced resonance light scattering (RLS). This method is
      based on the specific recognition and signal amplification of adenosine aptamer
      (Apt) coupled with gold nanoparticles (GNPs) via G-quartet-induced nanoparticle
      assembly, which was fabricated by triggering a structure switching of the 3'
      terminus G-rich sequence and aptamer duplex. RLS signal linearly correlated with
      the concentration of adenosine over the range of 6-115nM. The limit of detection
      (LOD) for adenosine is 1.8nM with relative standard deviations (RSD) of 2.90
      4.80% (n=6). The present method has been successfully applied to determination of
      adenosine in real human urine, and the obtained results were in good agreement
      with those obtained by the HPLC method. Our investigation shows that the
      combination of the excellent selectivity of aptamer with the high sensitivity of
      the RLS technique could provide a promising potential for aptamer-based small
      molecule detection, and be beneficial in extending the application of RLS.

PMID- 19849998
TI  - Europium-labeled GTP as a general nonradioactive substitute for [(35)S]GTPgammaS
      in high-throughput G protein studies.
AB  - [(35)S]GTPgammaS, the nonhydrolyzable radioactive GTP analog, has been a powerful
      tool in G protein studies and has set the standards in this field of research.
      However, its radioactive nature imposes clear limitations to its use in regular
      laboratory practice and in high-throughput experimentation. The europium-labeled
      GTP analog (Eu-GTP) has been used as an alternative in the analysis of G protein
      activation by G protein-coupled receptors in cellular membrane preparations. Here
      we expand the usage of Eu-GTP and show that it can be applied in other types of
      assays where [(35)S]GTPgammaS has been previously utilized. We demonstrate the
      applicability of the modified Eu-GTP binding technology to analysis of
      heterotrimeric and monomeric G proteins of natural and recombinant sources, from
      different organisms, in assays with soluble proteins and membrane-containing
      assays of a high-throughput format. The deci-nanomolar K(D) of Eu-GTP for the
      tested G proteins is similar to that of other fluorescent-modified GTP analogs,
      while the sensitivity achieved in time-resolved fluorescence analysis of Eu-GTP
      exceeds that of the radioactive measurements. Overall, the results of our
      modified Eu-GTP binding assay present Eu-GTP as a general nonradioactive
      alternative for G protein studies, especially attractive in high-throughput
      experiments.

PMID- 19849999
TI  - Analysis of activity and inhibition of oxygen-dependent enzymes by optical
      respirometry on the LightCycler system.
AB  - There is currently a need for a method capable of measuring the activity and
      inhibition of biologically relevant oxygenases in a format that enables the
      convenient, fast, and cost-efficient generation of dose-response information.
      Here we describe a low-volume luminescence-based assay for the measurement of
      such oxygen-dependent enzymes. The assay employs a photoluminescent oxygen
      sensitive probe and glass capillary microcuvettes measured on the Roche
      LightCycler detection platform. Three discrete types of oxygen probe were
      evaluated for this application: (i) solid-state coatings, (ii) soluble
      macromolecular MitoXpress probe, both phosphorescent porphyrin-based, and (iii) a
      luminescent Ir(III)-based nanoparticle probe. Measurement parameters were
      optimised and subsequently applied to the analysis of three biologically relevant
      oxygenases, namely cytochrome P450 (CYP), monoamine oxygenase (MAO), and
      cyclooxygenase (COX). CYP enzymes are central players in drug detoxification
      while specific inhibitors of MAO and COX are important for therapeutic
      intervention and treatment of neurological and inflammatory diseases,
      respectively. To determine assay utility, oxygen consumption catalysed by all
      three enzyme types was measured and the effect of specific inhibitors determined.
      The panel included the MAO-A/B inhibitors clorgyline, toloxatone, deprenyl, and
      the COX-1/2 inhibitors niflumic acid, nimesulide, SC-560, ketoprofen, and
      phenylbutazone. IC(50) values were then compared with literature values. The
      measurement methodology described allows the low-volume analysis of biologically
      relevant oxygenases and displays the requisite sensitivity and throughput to
      facilitate routine analysis. It is also applicable to other O(2)-dependent
      enzymes and enzymatic systems.

PMID- 19850000
TI  - Comparison of approaches for purifying and desalting polymerase chain reaction
      products prior to electrospray ionization mass spectrometry.
AB  - We have compared the recovery and desalting efficiency of different methods
      (ethanol precipitation, dialysis/ultrafiltration, purification with commercial
      kits, anion-exchange chromatography) of purifying and desalting PCR products
      prior to analysis by high-resolution/high mass accuracy electrospray ionization
      mass spectrometry (LTQ-Orbitrap). The results support the use of anion-exchange
      chromatography, which shows excellent desalting efficiency with almost no adducts
      observed, along with a recovery of approximately 70% and the ability to purify
      approximately 10 samples in 45 min.

PMID- 19850001
TI  - Endotoxin assay by bioluminescence using mutant firefly luciferase.
AB  - The Limulus reaction is an application of the defense mechanism of horseshoe crab
      for endotoxin detection. Endotoxin is a component of the cell wall in the outer
      membrane of gram-negative bacteria, and causes fever or shock when it enters the
      human blood stream. For endotoxin detection, gel formation or turbidity of the
      coagulation factor chromogen or fluorescence-modified peptide is used. However,
      these conventional methods have problems with regard to their measurement time or
      sensitivity. We recently obtained a mutant firefly luciferase that has a
      luminescence intensity over 10-fold higher than that of the wild type. Therefore,
      we developed a new endotoxin detection method that combines the Limulus reaction
      and bioluminescence using mutant luciferase. The new method detects 0.0005EU/ml
      of endotoxin within 15min.

PMID- 19850002
TI  - Flavin-containing heme enzymes.
AB  - There are many examples of oxidative enzymes containing both flavin and heme
      prosthetic groups that carry out the oxidation of their substrate. For the
      purpose of this article we have chosen five systems. Two of these, the L-lactate
      dehydrogenase flavocytochrome b(2) and cellobiose dehydrogenase, carry out the
      catalytic chemistry at the flavin group. In contrast, the remaining three require
      activation of dioxygen at the heme group in order to accomplish substrate
      oxidation, these being flavohemoglobin, a nitric oxide dioxygenase, and the mono
      oxygenases nitric oxide synthase and flavocytochrome P450 BM3, which functions as
      a fatty acid hydroxylase. In the light of recent advances we will describe the
      structures of these enzymes, some of which share significant homology. We will
      also discuss their diverse and sometimes controversial catalytic mechanisms, and
      consider electron transfer processes between the redox cofactors in order to
      provide an overview of this fascinating set of enzymes.

PMID- 19850003
TI  - The conformation of end-groups is one determinant of carotenoid topology suitable
      for high fidelity molecular recognition: a study of beta- and epsilon-end-groups.
AB  - Conformation affects a carotenoid's ability to bind selectively to proteins. We
      calculated adiabatic energy profiles for rotating the ring end-groups around the
      C6C7 bond and for flexing of the ring with respect to the polyene chain. The
      choice of computational methods is important. A low, 4.2 kcal/mol barrier to
      rotation exists for a beta-ring. An 8.3 kcal/mol barrier exists for rotation of
      an epsilon-ring. Rotation of the epsilon-ring is sensitive to substitution at C3.
      In the absence of external forces neither beta- nor epsilon-rings are
      rotationally constrained. The nearly parallel alignment of the beta-ring to the
      C6C7 bond axis contrasts to the more perpendicular orientation of the epsilon
      ring. Flexion of a beta-ring to the minimized epsilon-ring conformation requires
      approximately 23 kcal/mol; extension of the epsilon-ring to the minimized beta
      ring conformation requires approximately 8 kcal/mol. Selectivity associated with
      beta- versus epsilon-rings is dominated by the inability of the beta-ring to flex
      to minimize protein/ring steric interactions and maximize van der Waal's
      attractions with the binding site.

PMID- 19850004
TI  - Comparative study of HOCl-inflicted damage to bacterial DNA ex vivo and within
      cells.
AB  - The prospects for using bacterial DNA as an intrinsic probe for HOCl and
      secondary oxidants/chlorinating agents associated with it has been evaluated
      using both in vitro and in vivo studies. Single-strand and double-strand breaks
      occurred in bare plasmid DNA that had been exposed to high levels of HOCl,
      although these reactions were very inefficient compared to polynucleotide chain
      cleavage caused by the OH.-generating reagent, peroxynitrite. Plasmid nicking was
      not increased when intact Escherichia coli were exposed to HOCl; rather, the
      amount of recoverable plasmid diminished in a dose-dependent manner. At
      concentration levels of HOCl exceeding lethal doses, genomic bacterial DNA
      underwent extensive fragmentation and the amount of precipitable DNA-protein
      complexes increased several-fold. The 5-chlorocytosine content of plasmid and
      genomic DNA isolated from HOCl-exposed E. coli was also slightly elevated above
      controls, as measured by mass spectrometry of the deaminated product, 5
      chlorouracil. However, the yields were not dose-dependent over the bactericidal
      concentration range. Genomic DNA recovered from E. coli that had been subjected
      to phagocytosis by human neutrophils occasionally showed small increases in 5
      chlorocytosine content when compared to analogous cellular reactions where
      myeloperoxidase activity was inhibited by azide ion. Overall, the amount of
      isolable 5-chlorouracil from the HOCl-exposed bacterial cells was far less than
      the damage manifested in polynucleotide bond cleavage and cross-linking.

PMID- 19850005
TI  - Influence of K+-dependent membrane lipid composition on the expression of the
      kdpFABC operon in Escherichia coli.
AB  - The membrane-bound sensor kinase KdpD and the cytoplasmic response regulator KdpE
      regulate the expression of the kdpFABC operon coding for the high affinity
      potassium uptake system KdpFABC in Escherichia coli. The signal transduction
      cascade of this two component system is activated under K(+)-limiting conditions
      in the medium, but is less sensitive to high osmolality. In order to test whether
      K(+) limitation affects membrane phospholipid composition and whether this change
      affects kdpFABC expression, we analysed the phospholipid composition of E. coli
      under these conditions. Our measurements revealed that there is an increase in
      the cardiolipin (CL) content during the exponential growth phase at the expense
      of the zwitterionic phospholipid phosphatidylethanolamine. The higher anionic
      phospholipid content occurs along with an increase of transcriptional activity of
      the cls gene coding for CL synthase. Furthermore, in vivo studies with E. coli
      derivatives carrying mutations in genes coding for enzymes involved in
      phospholipid biosynthesis revealed that the increase in the anionic lipid
      composition enhances the expression rate of the kdpFABC operon. Finally, we show
      that kinase activity of KdpD is stimulated in its native membrane environment by
      fusion with liposomes of anionic, but reduced with liposomes of zwitterionic
      phospholipids.

PMID- 19850006
TI  - Influence of membrane curvature on the structure of the membrane-associated
      pleckstrin homology domain of phospholipase C-delta1.
AB  - The effects of geometric properties of membranes on the structure of the
      phospholipase C-delta1 (PLC-delta1) pleckstrin homology (PH) domain were
      investigated using solid state (13)C NMR spectroscopy. Conformations of the PLC
      delta1 PH domain at the surfaces of multilamellar vesicles (MLV), small
      unilamellar vesicles (SUV), and micelles were examined to evaluate the effects of
      membrane curvature on the PH domain. An increase in curvature of the water
      hydrophobic layer interface hinders membrane-penetration of the amphipathic
      alpha2-helix of the PH domain that assists the membrane-association of the PH
      domain dominated by the phosphatidylinositol 4,5-bisphosphate (PIP(2)) specific
      lipid binding site. The solid state (13)C NMR signal of Ala88 located at the
      alpha2-helix indicates that the conformation of the alpha2-helix at the micelle
      surface is similar to the solution conformation and significantly different from
      those at the MLV and SUV surfaces which were characterized by membrane
      penetration and re-orientation. The signal of Ala112 which flanks the C-terminus
      of the beta5/beta6 loop that includes the alpha2-helix, showed downfield
      displacement with decrease in the interface curvature of the micelles, SUV and
      MLV. This reveals that the conformation of the C-terminus of the beta5/beta6 loop
      connecting the beta-sandwich core containing the PIP(2) binding site and the
      amphipathic alpha2-helix is sensitive to alterations of the curvature of lipid
      bilayer surface. It is likely that these alterations in the conformation of the
      PLC-delta1 PH domain contribute to the regulatory mechanisms of the intracellular
      localization of PLC-delta1 in a manner dependent upon the structure of the
      molecular complex containing PIP(2).

PMID- 19850008
TI  - Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma
      associated ITK-SYK fusion-protein.
AB  - Recurrent chromosomal translocations have long been implicated in various types
      of lymphomas and other malignancies. Novel recurrent t(5;9)(q33;q22) has been
      recently discovered in un-specified peripheral T-cell lymphoma. To elucidate the
      role of this translocation, the corresponding fusion construct encoding the N
      terminal portion of the ITK kinase and the C-terminal catalytic region of the SYK
      kinase was generated. We herein show that the ITK-SYK fusion-protein is
      constitutively active. Moreover, we demonstrate that ITK-SYK is phosphorylated on
      key tyrosine residues and is capable of potently phosphorylating the related
      adapter proteins BLNK and SLP-76. In transiently transfected cells, SYK was
      phosphorylated at Y352 but not detectably at the activation-loop tyrosines
      Y525/Y526. In contrast, ITK-SYK was phosphorylated both at Y212 and the
      activation-loop tyrosines Y385/Y386, corresponding to Y352 and Y525/Y526 in SYK,
      respectively. In resting primary lymphocytes, ITK-SYK predominantly localizes to
      the cell surface. In addition, we demonstrate that following stimulation, the ITK
      SYK fusion-protein in cell lines translocates to the cell membrane and, moreover,
      that this phenomenon as well as SLP-76 phosphorylation are blocked upon
      phosphatidylinositol-3-kinase (PI3-kinase) inhibition.

PMID- 19850007
TI  - Loss of ovarian function in mice results in abrogated skeletal muscle PPARdelta
      and FoxO1-mediated gene expression.
AB  - Menopause, the age-related loss of ovarian hormone production, promotes increased
      adiposity and associated metabolic pathology, but molecular mechanisms remain
      unclear. We previously reported that estrogen increases skeletal muscle PPARdelta
      expression in vivo, and transgenic mice overexpressing muscle-specific PPARdelta
      are reportedly protected from diet-induced obesity. We thus hypothesized that
      obesity observed in ovariectomized mice, a model of menopause, may result in part
      from abrogated expression of muscle PPARdelta and/or downstream mediators such as
      FoxO1. To test this hypothesis, we ovariectomized (OVX) or sham-ovariectomized
      (SHM) 10-week old female C57Bl/6J mice, and subsequently harvested quadriceps
      muscles 12weeks later for gene expression studies. Compared to SHM, muscle from
      OVX mice displayed significantly decreased expression of PPARdelta (3.4-fold),
      FoxO1 (4.5-fold), PDK-4 (2.3-fold), and UCP-2 (1.8-fold). Consistent with studies
      indicating PPARdelta and FoxO1 regulate muscle fiber type, we observed dramatic
      OVX-specific decreases in slow isoforms of the contractile proteins myosin light
      chain (11.1-fold) and troponin C (11.8-fold). In addition, muscles from OVX mice
      expressed 57% less myogenin (drives type I fiber formation), 2-fold more MyoD
      (drives type II fiber formation), and 1.6-fold less musclin (produced exclusively
      by type II fibers) than SHM, collectively suggesting a shift towards less type I
      oxidative fibers. Finally, and consistent with changes in PPARdelta and FoxO1
      activity, we observed decreased expression of atrogin-1 (2.3-fold) and MuRF-1
      (1.9-fold) in OVX mice. In conclusion, muscles from ovariectomized mice display
      decreased PPARdelta and FoxO1 expression, abrogated expression of downstream
      targets involved in lipid and protein metabolism, and gene expression profiles
      indicating less type I oxidative fibers.

PMID- 19850009
TI  - Comparison of the anorexigenic activity of CRF family peptides.
AB  - Corticotropin releasing factor (CRF) family peptides have an important role in
      the control of food intake. We investigated the effects of CRF family peptides on
      food intake and body weight gain in mice. Of the CRF family peptides, including
      CRF, urocortin1 (Ucn1), urocortin2 (Ucn2) and urocortin3 (Ucn3), peripherally
      administered Ucn1 was shown to have the most potent inhibitory effect on the food
      intake and body weight gain of both lean and high fat fed obese mice. In
      addition, repeated administration of Ucn1 lowered blood glucose and acylated
      ghrelin, and decreased the visceral fat weight of high fat fed obese mice.

PMID- 19850010
TI  - Amantadine- and oseltamivir-resistant variants of influenza A viruses in
      Thailand.
AB  - Amantadine and oseltamivir are used to treat influenza A virus infections;
      however, resistance to these drugs has been widely reported throughout the world.
      In this study, the frequency and genetic characteristics of the drug-resistant
      influenza A viruses that circulated in Thailand from 2006 to 2008 were
      investigated. The nucleotide sequences of the NA and M2 genes were elucidated in
      order to identify mutations that confer oseltamivir- and amantadine-resistant
      phenotypes, respectively. A total of 66 influenza A viruses including 44 H1N1 and
      22 H3N2 subtypes isolated in Bangkok and 13 provinces of Thailand from 2006 to
      2008 were analyzed. Our results demonstrated that seven out of 32 (22%) of the
      H1N1 viruses isolated in 2006 in Thailand carried the amino acid S31N
      substitution, which confers amantadine-resistance, although no isolates in 2007
      or 2008 possessed the mutation. In the cases of oseltamivir-resistance, four of
      10 (40%) of the H1N1 viruses isolated in 2008 were predicted to be resistant to
      the drug, although none of the 34 viruses isolated in 2006 or 2007 were predicted
      to be resistant. Surprisingly, all 9 H3N2 viruses isolated in 2008 appeared to be
      resistant to the amantadine and none were resistant in 2006 or 2007. Phylogenetic
      analysis based on the HA, M, and NA genes demonstrated that the amantadine
      resistant H1N1 isolates had been produced by genetic reassortment. All of the
      amantadine-resistant H3N2 viruses were clustered in one of these three genes and
      possessed double mutations of S193F and D225N in the HA gene.

PMID- 19850011
TI  - Stabilins are expressed in bone marrow sinusoidal endothelial cells and mediate
      scavenging and cell adhesive functions.
AB  - Bone marrow sinusoidal endothelial cells have a specific function as a site of
      transmigration of hematopoietic stem and progenitor cells and mature blood cells
      between bone marrow and blood stream. However, the specific characteristics of
      bone marrow sinusoidal endothelial cells are still largely unclear. We here
      report that these cells express stabilin-1 and stabilin-2, which in liver
      sinusoidal endothelial cells have been identified as endocytic scavenger
      receptors for several ligands, including SPARC and hyaluronan. We show here that
      intravenously injected formaldehyde-treated serum albumin, advanced glycation end
      products, and collagen I alpha-chains were taken up by bone marrow sinusoidal
      endothelial cells, showing that these cells have a scavenging function and
      thereby may modulate bone marrow vascular stem cell niches. Importantly, we show
      hyaluronan mediated adhesion of hematopoietic stem and progenitor cells to
      stabilin-2-transfected cells, suggesting that stabilin-2 contributes to adhesion
      and homing of circulating stem and progenitor cells to bone marrow.

PMID- 19850012
TI  - A novel l-isoleucine hydroxylating enzyme, l-isoleucine dioxygenase from Bacillus
      thuringiensis, produces (2S,3R,4S)-4-hydroxyisoleucine.
AB  - The unique function of 4-hydroxyisoleucine (4-HIL) is to stimulate glucose
      induced insulin secretion in a glucose-dependent manner. 4-HIL is distributed
      only in certain kinds of plants and mushrooms, but the biosynthetic mechanism of
      4-HIL has not been elucidated. Moreover, 4-HIL-producing microorganisms have not
      been reported. l-isoleucine (l-Ile) hydroxylating activity producing 4-HIL was
      detected in a cell lysate of Bacillus thuringiensis strain 2e2 AKU 0251 obtained
      from the mid-late exponential phase of growth. Properties of the purified
      hydroxylase demonstrated that it is a alpha-ketoglutaric acid (alpha-KG)
      dependent l-Ile dioxygenase (IDO) and requires alpha-KG, ferric ion, and ascorbic
      acid for its maximum activity. IDO showed high stereoselectivity in l-Ile
      hydroxylation producing only (2S,3R,4S)-4-HIL. The N-terminal 22 amino acids
      sequence revealed high homology to a hypothetical protein (GenBank ID:
      RBTH_06809) in B. thuringiensis serovar israelensis ATCC 35646. The histidine
      motif, which is conserved in alpha-KG dependent dioxygenases, is found in
      RBTH_06809.

PMID- 19850013
TI  - Irreversibly glycated LDL induce oxidative and inflammatory state in human
      endothelial cells; added effect of high glucose.
AB  - In diabetes, hyperglycemia and the associated formation of advanced glycation end
      products (AGE) and AGE-modified low density lipoproteins (AGE-LDL) can directly
      affect the cells of the vascular wall. We hypothesize that AGE-LDL may act
      directly and induce oxidant and inflammatory alterations in human endothelial
      cells (HEC), this effect being amplified by high glucose. To test this
      assumption, the activity of NADPH oxidase (NADPHox) was evaluated and the
      expression of its subunits (p22(phox), NOX4, and p67(phox)), of the AGE receptor
      (RAGE), and of the monocyte chemoattractant protein-1 (MCP-1) were assessed by
      real-time PCR and Western blot in confluent EA.hy926 cells incubated with AGE-LDL
      for 24 and 48h, in normal and high glucose conditions. Exposure of HEC for 48h to
      AGE-LDL in 5mM glucose induced an increase of RAGE expression (50%), NADPHox
      activity (107%), p22(phox) and NOX4 mRNA (50% and 188%, respectively) and MCP-1
      expression (80%). AGE-LDL-stimulated p22(phox) expression by activating p38 MAP
      kinase and NF-kB, and MCP-1 expression by activating NF-kB, as demonstrated by
      the use of specific inhibitors (SB203580 and Bay11-7085). The addition of 25mM
      glucose in the culture medium enhanced the effect of AGE-LDL, but also of nLDL,
      on RAGE, p22(phox), NOX4, p67(phox), and MCP-1 gene expression. In conclusion,
      AGE-LDL induce an oxidative stress and a pro-inflammatory state in human
      endothelial cells. Both AGE-LDL and nLDL in the presence of high glucose amplify
      their effect, revealing a link between hyperlipidemia, diabetes, and endothelial
      cell dysfunction.

PMID- 19850014
TI  - Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression
      through protein kinase A pathway and prevents inflammatory adipokine expression.
AB  - Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that has
      been used as a drug injected subcutaneously for treatment of type 2 diabetes.
      Many studies have revealed molecular targets of Ex-4, but its influence on
      adipokines has not been determined. Our study showed that Ex-4 induced secretion
      of adiponectin into the culture medium of 3T3-L1 adipocytes. This effect of Ex-4
      is due to increased adiponectin mRNA level through the GLP-1R. Both forskolin and
      3-isobutyl-1-methylxanthine (IBMX), which may finally elevate cyclic adenosine
      monophosphate (cAMP) concentration, prevented the induction of adiponectin
      expression by Ex-4. Moreover, H89, a protein kinase A inhibitor, blocked the
      effect of Ex-4 on adiponectin. On the other hand, Ex-4 decreased the mRNA levels
      of inflammatory adipokines. The results indicate that Ex-4 directly promotes
      adiponectin secretion via the protein kinase A pathway in 3T3-L1 adipocytes and
      may ameliorate insulin resistance.

PMID- 19850015
TI  - Inhibitory mechanisms following electrical stimulation of tendon and cutaneous
      afferents in the lower limb.
AB  - Electrical stimulation of the Achilles tendon (TES) produced strong reflex
      depression (duration>250 ms) of a small background contraction in both heads of
      gastrocnemius (GA) via large diameter electrodes localized to the tendon. The
      inhibitory responses were produced without electrical (M wave) or mechanical
      (muscle twitch) signs of direct muscle stimulation. In this study, the
      contribution of presynaptic and postsynaptic mechanisms to the depression was
      investigated by studying conditioning effects of tendon afferent stimulation on
      the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES
      completely inhibited the TR over an ISI of 300 ms that commenced before and
      continued during and after the period of voluntary EMG depression. Tendon
      afferent conditioning stimuli also partially inhibited the MEP, but over a short
      time course confined to the period of voluntary EMG depression. The strength and
      extended time course of tendon afferent conditioning of the TR and its failure to
      produce a similar depression of the MEP are consistent with a mechanism involving
      presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent
      conditioning partially inhibited the TR and MEP over a short time course (ISI
      <100 ms) resembling the inhibition seen in the voluntary EMG. This was consistent
      with the postsynaptic origin of cutaneous inhibition of the motoneurons.

PMID- 19850016
TI  - Genetic and expression analysis of all 7 non-synonymous single nucleotide
      polymorphisms in the human deoxyribonuclease II gene, with potential relevance to
      autoimmunity.
AB  - BACKGROUND: Several non-synonymous SNPs in the human DNase II gene, potentially
      relevant to autoimmunity, have been identified, but only limited population data
      are available. Also, the effects of these SNPs on the catalytic activity of the
      enzyme remain unknown. METHODS: Genotyping of all the non-synonymous SNPs was
      performed in healthy subjects of 3 ethnic groups including 6 different
      populations using the PCR-RFLP technique. A series of mutants corresponding to
      each SNP was expressed in COS-7 cells and its activity was measured. RESULTS:
      Five of the populations, including Japanese, Germans, Turks, Ghanaians and
      Ovambos, were typed as a single genotype at each SNP, but Koreans were not.
      Constructs derived from minor alleles at A58del, V284M, R298L and Q322Term
      exhibited drastically low or almost no activity. CONCLUSION: The DNase II gene
      shows relatively low genetic diversity with regard to these non-synonymous SNPs,
      suggesting that the enzyme has been well conserved. A minor allele at V284M is
      distributed with a frequency of 0.013 in the database, and it seems plausible
      that levels of DNase II activity for the heterozygote are lower than those in
      individuals with the predominant homozygote. Our results may have clinical
      implications in relation to the prevalence of autoimmune diseases.

PMID- 19850018
TI  - High-throughput liquid-liquid extraction and LCMSMS assay for determination of
      circulating 25(OH) vitamin D3 and D2 in the routine clinical laboratory.
AB  - BACKGROUND: Increasing focus on vitamin D as essential to health has underscored
      the need for accurate and precise high-throughput measurement of serum 25(OH)D.
      METHODS: Serum was denatured in acetonitrile containing hexadeuterated 25(OH)D3
      as internal standard (IS) and automatically applied to filter plates packed with
      inert diatomous earth material for subsequent heptane extraction. Extracts were
      chromatographed on a C12 HPLC column, and detected on a triple quadropole mass
      spectrometer. RESULTS: The inter-assay precision was 9.4% and 8.8% respectively
      at 32.0 and 59.7 nmol/l for 25(OH)D3 and 8.6% and 8.0% at 23.4 and 64.4 nmol/l
      for 25(OH)D2. The detection limit was 10 nmol/l for both metabolites. Three
      percent of samples contained >50 nmol/l 25(OH)D2. Total run time was 4 min. We
      have performed more than 200,000 routine samples and the method performs well in
      external control schemes. CONCLUSION: We describe a robust, high-throughput, LLE
      LCMSMS method for accurate and precise quantitation of 25(OH)D3 and 25(OH)D2 in
      serum. The use of diatomaceous earth material for extraction of vitamin D in 96
      well format enables fast, simple and efficient sample preparation. The method
      offers a cost-effective alternative to immunological methods for use in the
      routine clinical biochemical laboratory.

PMID- 19850017
TI  - Automation of the Hepascore and validation as a biochemical index of liver
      fibrosis in patients with chronic hepatitis C from the ANRS HC EP 23 Fibrostar
      cohort.
AB  - BACKGROUND: Hepascore combining serum bilirubin, gamma glutamyl transpeptidase,
      hyaluronic acid (HA) and alpha2-macroglobulin with age and sex, was reported as
      relevant in predicting liver fibrosis in patients with chronic HCV infection and
      was proposed as an alternative to liver biopsy. METHODS: Since an automated HA
      assay (Latex method, Wako, Japan) became available, we investigated to automate
      Hepascore by simultaneous measurements of components using an OLYMPUS AU640
      analyzer (Tokyo, Japan). For its clinical evaluation, we considered a cohort of
      chronic HCV patients included in a multicenter prospective study (ANRS HC EP 23
      Fibrostar). RESULTS: Automated Hepascore was not significantly different than
      assayed as previously described. An improvement in HA variability was evidenced.
      In 512 chronic HCV patients, automated Hepascore, using ROC curves analysis,
      showed good predictive performances for significant fibrosis (AUROC=0.81), severe
      fibrosis (AUROC=0.82), and cirrhosis (AUROC=0.88). For significant fibrosis,
      Hepascore (cut-off=0.5) had a sensitivity of 0.77, a specificity of 0.70, a
      positive predictive value of 0.71 and a negative predictive value (NPV) of 0.77.
      Hepascore <0.25 could exclude significant fibrosis with a sensitivity of 0.95 and
      a NPV of 0.90 and Hepascore <0.75 could exclude cirrhosis with a sensitivity of
      0.86 and a NPV of 0.97. CONCLUSIONS: This study shows that Hepascore, a non
      invasive index of liver fibrosis, necessitating only one serum sample, can be
      totally automated using a single analyzer and confirms that Hepascore accurately
      predicts liver fibrosis in chronic HCV. Hepascore might be largely used in
      assessing liver fibrosis as surrogate to the liver biopsy.

PMID- 19850019
TI  - Human plasma concentrations of malondialdehyde (MDA) and the F2-isoprostane 15(S)
      8-iso-PGF(2alpha) may be markedly compromised by hemolysis: evidence by GC-MS/MS
      and potential analytical and biological ramifications.
AB  - OBJECTIVES: Malondialdehyde (MDA) and the F(2)-isoprostane 15(S)-8-iso
      prostaglandin F(2alpha) (15(S)-8-iso-PGF(2alpha)) belong to the most frequently
      analyzed biomarkers of oxidative stress in basic and clinical research. The
      objective of the present study was to examine the effect of hemolysis on free MDA
      and total (free+esterified) 15(S)-8-iso-PGF(2alpha) concentrations in human
      plasma. DESIGN AND METHODS: MDA and 15(S)-8-iso-PGF(2alpha) were determined by GC
      MS/MS in plasma samples from venous heparinized blood drawn under resting
      conditions (n=22) as well as under physical exercise (n=158) in 22 healthy young
      subjects. In vitro, we prepared plasma samples with hemolysis degrees up to 0.8%
      using artificially hemolyzed, freshly obtained heparinized blood. RESULTS: In
      some plasma samples of the exercise study both under resting and exercise
      conditions, clinically significant hemolysis was macroscopically visible. Both in
      vivo (r=0.74) and in vitro (r=0.87), we found a significant positive correlation
      between hemolysis degree (0-0.2%) and MDA plasma concentrations (50-250 nmol/L).
      Unlike in vitro (r=0.84), in vivo, 15(S)-8-iso-PGF(2alpha) and MDA plasma
      concentrations correlated weakly (r=0.50). CONCLUSIONS: We hypothesize that free
      hemoglobin catalyzes the formation of MDA and 15(S)-8-iso-PGF(2alpha) from free
      and esterified arachidonic acid. Plasma concentrations of MDA and total 15(S)-8
      iso-PGF(2alpha) may be markedly compromised by hemolysis. Measurements of MDA and
      15(S)-8-iso-PGF(2alpha) should be treated with caution regarding involvement of
      oxidative stress in disease as well as in health both under resting conditions
      and under exercise.

PMID- 19850021
TI  - Serum levels of vascular endothelial growth factor and its receptors in patients
      with severe autism.
AB  - OBJECTIVE: To study vascular endothelial growth factor (VEGF) and its soluble
      receptors sVEGFR-1 and -2 in autism. DESIGN AND METHODS: We measured serum levels
      of angiogenic molecules in 22 patients with severe autism and 28 controls.
      RESULTS: Patients and controls had similar sVEGFR-2 levels, but VEGF levels were
      lower and sVEGFR-1 higher in patients with autism. CONCLUSION: The imbalance
      between VEGF and its receptor sVEGFR-1 may be involved in the pathophysiology of
      autism.

PMID- 19850020
TI  - Proatherogenic disturbances in lipoprotein profile, associated enzymes and
      transfer proteins in women with iron deficiency anaemia.
AB  - OBJECTIVE: To characterize the lipid-related atherogenic risk factors in iron
      deficiency anaemia (IDA) patients. DESIGN AND METHODS: Twenty IDA women were
      compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester
      transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated
      phospholipase A(2) (LpPLA(2)) activities and plasma levels of oxidized-LDL were
      evaluated. RESULTS: Triglycerides were higher (median [range]) (1.0 [0.5-1.9] vs.
      0.7 [0.5-1.5] mmol/L, p<0.05) and HDL-C lower (mean + or - SD) (1.3 + or - 0.3
      vs. 1.6 + or - 0.4 mmol/L, p<0.01) in the patients group. CETP (197 + or - 29%
      vs. 151 + or - 29% mL(-1) h(-1), p<0.001), PON 1 (122 + or - 17 vs. 140 + or - 33
      micromol mL(-1) min(-1), p<0.05) and LpPLA(2) (9.6 + or - 2.0 vs. 8.1 + or - 1.7
      micromol mL(-1) h(-1), p<0.05) activities were different in IDA women. No
      difference was observed in oxidized-LDL. Haemoglobin correlated negatively with
      triglycerides (r=-0.35, p<0.05), CETP (r=-0.62, p<0.001) and LpPLA(2) (r=-0.34,
      p<0.05), while ferritin was positively associated with HDL-C (r=0.39, p<0.05) and
      inversely with CETP (r=-0.49, p<0.005). CONCLUSION: The alterations in
      lipoprotein profile, CETP, PON 1 and LpPLA(2) activities described in the present
      study indicate that non-treated IDA might represent a proatherogenic state.

PMID- 19850022
TI  - SELDI-TOF biomarker signatures for cystic fibrosis, asthma and chronic
      obstructive pulmonary disease.
AB  - OBJECTIVES: The aim of this work was to establish protein profiles in serum and
      nasal epithelial cells of cystic fibrosis individuals in comparison with
      controls, asthma and chronic obstructive pulmonary disease patients for specific
      biomarker signatures identification. DESIGN AND METHODS: Protein extracts were
      analyzed by Surface Enhanced Laser Desorption/Ionization Time-Of-Flight Mass
      Spectrometry (SELDI-TOF-MS). RESULTS: The mass spectra revealed a set of peaks
      with differential expression in serum and nasal cells among the different groups
      studied, resulting into peak signatures representative/specific of each
      pathology. Logistic regressions were applied to those peaks; sensitivity,
      specificity, Youden's indexes and area under the curve (AUC) of the respective
      receiver operating characteristic (ROC) curves were compared. DISCUSSION:
      Multivariate analysis demonstrated that combination of peaks has a better
      predictive value than the individual ones. These protein signatures may serve as
      diagnostic/prognostic markers for the studied diseases with common clinical
      features, or as follow-up assessment markers of therapeutic interventions.

PMID- 19850023
TI  - Cells from an anhydrobiotic chironomid survive almost complete desiccation.
AB  - Dry-preservation of nucleated cells from multicellular animals represents a
      significant challenge in life science. As anhydrobionts can tolerate a desiccated
      state, their cells and organs are expected to show high desiccation tolerance in
      vitro. In the present study, we established cell lines derived from embryonic
      tissues of an anhydrobiotic chironomid, Polypedilum vanderplanki, designated as
      Pv11 and Pv210. Salinity stress induced the expression of a set of anhydrobiosis
      related genes in both Pv11 and Pv210 cells, suggesting that at least a part of
      cells can autonomously control the physiological changes for the entry into
      anhydrobiosis. When desiccated with medium supplemented with 300 mM trehalose or
      sucrose and stored for 4 weeks in dry air (approximately 5% relative humidity), a
      small percentage of the cells was found to be viable upon rehydration, although
      surviving cells seemed not to be able to multiply. We also attempted dry
      preservation of organs isolated from P. vanderplanki larvae, and found that a
      proportion of cells in some organs, including fat body, testis, nerve and dorsal
      vessel, tolerated in vitro desiccation.

PMID- 19850024
TI  - Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis.
AB  - Wnt signaling has been implicated in somite, limb, and branchial arch myogenesis
      but the mechanisms and roles are not clear. We now show that Wnt signaling via
      Lef1 acts to regulate the number of premyogenic cells in somites but does not
      regulate myogenic initiation in the limb bud or maintenance in the first or
      second branchial arch. We have also analysed the function and regulation of a
      putative downstream transcriptional target of canonical Wnt signaling, Pitx2. We
      show that loss-of-function of Pitx2 decreases the number of myogenic cells in the
      somite, whereas overexpression increases myocyte number particularly in the
      epaxial region of the myotome. Increased numbers of mitotic cells were observed
      following overexpression of Pitx2 or an activated form of Lef1, suggesting an
      effect on cell proliferation. In addition, we show that Pitx2 expression is
      regulated by canonical Wnt signaling in the epaxial somite and second branchial
      arch, but not in the limb or the first branchial arch. These results suggest that
      Wnt/Lef1 signaling regulates epaxial myogenesis via Pitx2 but that this link is
      uncoupled in other regions of the body, emphasizing the unique molecular networks
      that control the development of various muscles in vertebrates.

PMID- 19850027
TI  - Autocrine and paracrine Shh signaling are necessary for tooth morphogenesis, but
      not tooth replacement in snakes and lizards (Squamata).
AB  - Here we study the role of Shh signaling in tooth morphogenesis and successional
      tooth initiation in snakes and lizards (Squamata). By characterizing the
      expression of Shh pathway receptor Ptc1 in the developing dentitions of three
      species (Eublepharis macularius, Python regius, and Pogona vitticeps) and by
      performing gain- and loss-of-function experiments, we demonstrate that Shh
      signaling is active in the squamate tooth bud and is required for its normal
      morphogenesis. Shh apparently mediates tooth morphogenesis by separate paracrine-
      and autocrine-mediated functions. According to this model, paracrine Shh
      signaling induces cell proliferation in the cervical loop, outer enamel
      epithelium, and dental papilla. Autocrine signaling within the stellate reticulum
      instead appears to regulate cell survival. By treating squamate dental explants
      with Hh antagonist cyclopamine, we induced tooth phenotypes that closely resemble
      the morphological and differentiation defects of vestigial, first-generation
      teeth in the bearded dragon P. vitticeps. Our finding that these vestigial teeth
      are deficient in epithelial Shh signaling further corroborates that Shh is needed
      for the normal development of teeth in snakes and lizards. Finally, in this
      study, we definitively refute a role for Shh signaling in successional dental
      lamina formation and conclude that other pathways regulate tooth replacement in
      squamates.

PMID- 19850025
TI  - Gata4 directs development of cardiac-inducing endoderm from ES cells.
AB  - The transcription factor Gata4 is essential for normal heart morphogenesis and
      regulates the survival, growth, and proliferation of cardiomyocytes. We tested if
      Gata4 can specify cardiomyocyte fate from an uncommitted stem or progenitor cell
      population, by developing a system for conditional expression of Gata4 in
      embryonic stem cells. We find that in embryoid body cultures containing even a
      low ratio of these cells, expression of Gata4 is sufficient to enhance
      significantly the generation of cardiomyocytes, via a non-cell-autonomous
      mechanism. The Gata4-expressing cells do not generate cardiac or other mesoderm
      derivatives. Rather, Gata4 expression directs the development of two types of
      Sox17+ endoderm. This includes an epCam+Dpp4+ subtype of visceral endoderm. In
      addition, Gata4 generates similar amounts of epCam+Dpp4- definitive endoderm
      enriched for Cxcr4, FoxA2, FoxA3, Dlx5 and other characteristic transcripts. Both
      types of endoderm express cardiac-inducing factors, including WNT antagonists
      Dkk1 and Sfrp5, although the visceral endoderm subtype has much higher cardiac
      inducing activity correlating with relatively enhanced levels of transcripts
      encoding BMPs. The Gata4-expressing cells eventually express differentiation
      markers showing commitment to liver development, even under conditions that
      normally support mesoderm development. The results suggest that Gata4 is capable
      of specifying endoderm fates that facilitate, with temporal and spatial
      specificity, the generation of cardiomyocyte progenitors from associated
      mesoderm.

PMID- 19850026
TI  - Regulation of smoothened by Drosophila G-protein-coupled receptor kinases.
AB  - The Hedgehog (Hh) signaling pathway plays a conserved and essential role in
      regulating development and homeostasis of numerous tissues. Cytoplasmic signaling
      is initiated by Smoothened (Smo), a G-protein-coupled receptor (GPCR) family
      member, whose levels and activity are regulated by the Hh receptor Patched (Ptc).
      In response to Hh binding to Ptc, Ptc-mediated repression of Smo is relieved,
      leading to Smo activation, surface accumulation, and downstream signaling. We
      find that downregulation of Drosophila Smo protein in Hh-responding imaginal disc
      cells is dependent on the activity of G-protein-coupled receptor kinase 2
      (Gprk2). By analyzing gain- and null loss-of-function phenotypes, we provide
      evidence that Gprk2 promotes Smo internalization subsequent to its activation,
      most likely by direct phosphorylation. Ptc-dependent regulation of Smo
      accumulation is normal in gprk2 mutants, indicating that Gprk2 and Ptc
      downregulate Smo by different mechanisms. Finally, we show that both Drosophila G
      protein-coupled receptor kinase orthologues, Gprk1 and Gprk2, act in a partially
      redundant manner to promote Hh signaling. Our results suggest that Smo is
      regulated by distinct Ptc-dependent and Gprk2-dependent trafficking mechanisms in
      vivo, analogous to constitutive and activity-dependent regulation of GPCRs. G
      protein-coupled receptor kinase activity is also important for efficient
      downstream signaling.

PMID- 19850028
TI  - Germline cyst formation and incomplete cytokinesis during Drosophila melanogaster
      oogenesis.
AB  - Germline cyst formation via incomplete cytokinesis (IC) is necessary to generate
      functional eggs and sperm in various organisms. Drosophila melanogaster oogenesis
      is an ideal system for studying IC. 29 stages of germline cyst formation can be
      identified in D. melanogaster oogenesis. We have defined necessary terminology to
      describe IC and have developed a method to measure the sizes of contractile rings
      and ring canals. Time course study of germline cyst formation demonstrates that
      contractile ring constriction proceeds to a defined end point unique for each
      mitotic division. Contractile rings constrict to a greater degree, resulting in
      smaller ring diameters, for each subsequent round of mitotic division. Contrary
      to conventional wisdom, ring canal growth is not initiated until well after the
      fourth mitotic division. Ring canals grow, in an orderly manner, with ring canals
      derived from the first mitotic division enlarging first followed by those from
      the second, then those from the third, and finally those from the fourth mitotic
      division. This work establishes a foundation for identifying genes specific for
      IC and for elucidating the molecular mechanism underlying this aspect of germline
      cyst formation.

PMID- 19850029
TI  - A critical role for sFRP proteins in maintaining caudal neural tube closure in
      mice via inhibition of BMP signaling.
AB  - Both the BMP and Wnt pathways have been implicated in directing aspects of dorsal
      neural tube closure and cell fate specification. However, the mechanisms that
      control the diverse responses to these signals are poorly understood. In this
      study, we provide genetic and functional evidence that the secreted sFRP1 and
      sFRP2 proteins, which have been primarily implicated as negative regulators of
      Wnt signaling, can also antagonize BMP signaling in the caudal neural tube and
      that this function is critical to maintain proper neural tube closure and dorsal
      cell fate segregation. Our studies thus reveal a novel role for specific sFRP
      proteins in balancing the response of cells to two critical extracellular
      signaling pathways.

PMID- 19850030
TI  - Mast cells contribute to the stromal microenvironment in mammary gland branching
      morphogenesis.
AB  - The stromal microenvironment regulates mammary gland branching morphogenesis. We
      have observed that mast cells are present in the mammary gland throughout its
      postnatal development and, in particular, are found around the terminal end buds
      and ductal epithelium of the pubertal gland. Mast cells contribute to allergy,
      inflammatory diseases, and cancer development but have not been implicated in
      normal development. Genetic and pharmacological disruption of mast cell function
      in the mammary gland revealed that mast cells are involved in rapid proliferation
      and normal duct branching during puberty, and this effect is independent of
      macrophage recruitment, which also regulates mammary gland development. For mast
      cells to exert their effects on normal morphogenesis required activation of their
      serine proteases and degranulation. Our observations reveal a novel role for mast
      cells during normal pubertal development in the mammary gland.

PMID- 19850032
TI  - The evolution of class V POU domain transcription factors in vertebrates and
      their characterisation in a marsupial.
AB  - POU5F1 (OCT4) encodes a master regulator of pluripotency that is present in all
      mammals. A paralogue, POU2, is also present in the genomes of marsupials and
      monotremes and is an orthologue of zebrafish pou2 and chicken POUV. We explored
      the evolution of class V POU domain transcription factors and show that POU5F1
      arose by gene duplication of pou2 early in the evolution of tetrapods and is not
      mammal-specific, as previously thought. Instead, either POU5F1 or POU2/POUV has
      become extinct independently in various lineages, although all gnathostomes
      appear to possess at least one or the other. In the tammar wallaby, POU5F1
      expression is limited to pluripotent cell types (embryonic tissues and germ
      cells). POU2 is similarly expressed in pluripotent tissues but is also expressed
      in a broad range of adult tissues. Thus, unlike POU5F1, the role of POU2 may not
      be restricted to pluripotent cell types but could have a related function such as
      maintaining multipotency in adult stem cells.

PMID- 19850031
TI  - A systematic approach to identify functional motifs within vertebrate
      developmental enhancers.
AB  - Uncovering the cis-regulatory logic of developmental enhancers is critical to
      understanding the role of non-coding DNA in development. However, it is
      cumbersome to identify functional motifs within enhancers, and thus few
      vertebrate enhancers have their core functional motifs revealed. Here we report a
      combined experimental and computational approach for discovering regulatory
      motifs in developmental enhancers. Making use of the zebrafish gene expression
      database, we computationally identified conserved non-coding elements (CNEs)
      likely to have a desired tissue-specificity based on the expression of nearby
      genes. Through a high throughput and robust enhancer assay, we tested the
      activity of approximately 100 such CNEs and efficiently uncovered developmental
      enhancers with desired spatial and temporal expression patterns in the zebrafish
      brain. Application of de novo motif prediction algorithms on a group of forebrain
      enhancers identified five top-ranked motifs, all of which were experimentally
      validated as critical for forebrain enhancer activity. These results demonstrate
      a systematic approach to discover important regulatory motifs in vertebrate
      developmental enhancers. Moreover, this dataset provides a useful resource for
      further dissection of vertebrate brain development and function.

PMID- 19850034
TI  - The effect of lithium chloride on WIN 55,212-2-induced tolerance in isolated
      guinea pig ileum.
AB  - Tolerance to most of the cannabinoid effects has been reported, either in humans
      or in other species. Pharmacodynamic properties of these agents are perceived to
      be responsible for this phenomenon. The effect of lithium was examined on
      tolerance to WIN 55,212-2, a synthetic cannabinoid, in guinea pig ileum, a
      functional model to examine the mode of action of cannabinoids. Ileum strips were
      mounted in bath containing 37 degrees C Tyrode, under 0.5 g resting tension. The
      pulses were delivered, via platinum electrode, to the tissue and subsequent
      twitches were recorded using PowerLab system. WIN 55,212-2 could inhibit
      electrically stimulated twitches of guinea pig ileum in a dose dependent manner
      (pD(2)=8.56+/-0.41). Tolerance to this effect could be induced by incubating
      isolated ileum for 4h with WIN 55,212-2 (3 x IC(50)) (pD(2)=6.36+/-0.26, degree
      of tolerance: 159.32) (P<0.01). Lithium (1mM) could interfere with the
      development of this cannabinoid-induced tolerance and restores the sensitivity of
      ileum to inhibitory action of WIN 55,212-2 either when strips were exposed to
      lithium chloride during 4h incubation period (pD(2)=7.26+/-0.39) (P>0.05 versus
      non-tolerant group) (degree of tolerance: 20.28), or when lithium was added
      immediately before examining the inhibitory action of WIN 55,212-2 (pD(2)=8.09+/
      0.33) (P<0.05 versus corresponding tolerant group) (degree of tolerance: 2.96).
      Upon these results, it appears reasonable to consider an interventional role for
      lithium which may be able to break the chain of development and/or expression of
      tolerance to WIN 55,212-2 in this experimental model.

PMID- 19850033
TI  - In vivo analysis in Drosophila reveals differential requirements of contact
      residues in Axin for interactions with GSK3beta or beta-catenin.
AB  - Proper regulation of the Wingless/Wnt signaling pathway is essential for normal
      development. The scaffolding protein Axin plays a key role in this process
      through interactions with Drosophila Shaggy and Armadillo. In the current
      studies, we used a yeast two-hybrid assay to identify ten amino acids in Axin
      that are critical for in vitro interaction with Shaggy and two for interaction
      with Armadillo. We then generated five Axin variants in which individual putative
      contact amino acids were mutated and compared their activity, as assayed by
      rescue of axin null mutant flies, to that of Axin lacking the entire Shaggy
      (AxinDeltaSgg) or Armadillo (AxinDeltaArm) binding domain. Although we expected
      these mutants to function identically to Axin in which the entire binding domain
      was deleted, we instead observed a spectrum of phenotypic rescue. Specifically,
      two point mutants within the Shaggy binding domain showed loss of activity
      similar to that of AxinDeltaSgg and dominantly interfered with complex function,
      whereas a third mutant allele, AxinK446E, retained most function. Two Axin point
      mutants within the Armadillo binding domain were weak alleles and retained most
      function. These findings demonstrate the importance of in vivo verification of
      the role of specific amino acids within a protein.

PMID- 19850035
TI  - Discovery of a novel class of targeted kinase inhibitors that blocks protein
      kinase C signaling and ameliorates retinal vascular leakage in a diabetic rat
      model.
AB  - Protein kinase C (PKC) family members such as PKCbetaII may become activated in
      the hyperglycemic state associated with diabetes. Preclinical and clinical data
      implicate aberrant PKC activity in the development of diabetic microvasculature
      abnormalities. Based on this potential etiological role for PKC in diabetic
      complications, several therapeutic PKC inhibitors have been investigated in
      clinical trials for the treatment of diabetic patients. In this report, we
      present the discovery and preclinical evaluation of a novel class of 3-amino
      pyrrolo[3,4-c]pyrazole derivatives as inhibitors of PKC that are structurally
      distinct from the prototypical indolocarbazole and bisindolylmaleimide PKC
      inhibitors. From this pyrrolo-pyrazole series, several compounds were identified
      from biochemical assays as potent, ATP-competitive inhibitors of PKC activity
      with high specificity for PKC over other protein kinases. These compounds were
      also found to block PKC signaling activity in multiple cellular functional
      assays. PF-04577806, a representative from this series, inhibited PKC activity in
      retinal lysates from diabetic rats stimulated with phorbol myristate acetate.
      When orally administered, PF-04577806 showed good exposure in the retina of
      diabetic Long-Evans rats and ameliorated retinal vascular leakage in a
      streptozotocin-induced diabetic rat model. These novel PKC inhibitors represent a
      promising new class of targeted protein kinase inhibitors with potential as
      therapeutic agents for the treatment of patients with diabetic microvascular
      complications.

PMID- 19850037
TI  - Parabrachiella jarai sp. nov. (Crustacea: Copepoda: Siphonostomatoida) parasitic
      on Sillago sihama (Actinopterygii: Perciformes: Sillaginidae).
AB  - The presently reported study provides a detailed morphological description of the
      female and the male of a new species of the genus Parabrachiella-Parabrachiella
      jarai sp. nov. The parasites were sampled from marine fish, silver sillago,
      Sillago sihama (Perciformes: Sillaginidae), captured in Malaysia in 1994 and Hong
      Kong in 1995. The new species bears some resemblance to Parabrachiella lata (Song
      et Chen, 1976) but differs from it in details of second antenna, mandible, and
      maxilliped. The genus Parabrachiella currently covers 67 species including those
      recently transferred from Neobrachiella Kabata, 1979. An amended generic
      diagnosis is proposed for Parabrachiella and Thysanote. Some members of
      Parabrachiella are herewith transferred to Thysanote and some Thysanote are now
      placed in Parabrachiella.

PMID- 19850036
TI  - Osteopontin induces beta-catenin signaling through activation of Akt in prostate
      cancer cells.
AB  - Secretion of osteopontin (OPN) by cancer cells is a known mediator of
      tumorigenesis and cancer progression in both experimental and clinical studies.
      Our work demonstrates that OPN can activate Akt, an important step in cancer
      progression. Both ILK and PI3K are integral proteins in the OPN/Akt pathway, as
      inhibition of either kinase leads to a loss of OPN-mediated Akt activation.
      Subsequent to OPN-induced Akt activation, we observe inactivation of GSK-3beta, a
      regulator of beta-catenin. Osteopontin stimulation leads to an overall increase
      in beta-catenin protein levels with a resultant transfer of beta-catenin to the
      nucleus. Through the nuclear import of beta-catenin, OPN increases both the
      transcription and protein levels of MMP-7 and CD44, which are known TCF/LEF
      transcription targets. This work describes an important aspect of cancer
      progression induced by OPN.

PMID- 19850038
TI  - OsBADH1 is possibly involved in acetaldehyde oxidation in rice plant peroxisomes.
AB  - Although rice (Oryza sativa L.) produces little glycine betaine (GB), it has two
      betaine aldehyde dehydrogenase (BADH; EC 1.2.1.8) gene homologs (OsBADH1 and
      OsBADH2). We found that OsBADH1 catalyzes the oxidation of acetaldehyde
      efficiently, while the activity of OsBADH2 is extremely low. The accumulation of
      OsBADH1 mRNA decreases following submergence treatment, but quickly recovers
      after re-aeration. We confirmed that OsBADH1 localizes in peroxisomes. In this
      paper, a possible physiological function of OsBADH1 in the oxidation of
      acetaldehyde produced by catalase in rice plant peroxisomes is discussed.

PMID- 19850039
TI  - ER exit sites--localization and control of COPII vesicle formation.
AB  - The first membrane trafficking step in the biosynthetic secretory pathway, the
      export of proteins and lipids from the endoplasmic reticulum (ER), is mediated by
      COPII-coated vesicles. In mammalian cells, COPII vesicle budding occurs at
      specialized sites on the ER, the so-called transitional ER (tER). Here, we
      discuss aspects of the formation and maintenance of these sites, the mechanisms
      by which cargo becomes segregated within them, and the propagation of ER exit
      sites (ERES) during cell division. All of these features are inherently linked to
      the formation, maintenance and function of the Golgi apparatus underlining the
      importance of ERES to Golgi function and more widely in terms of intracellular
      organization and cellular function.

PMID- 19850040
TI  - Nucleolar disruption impairs Kaposi's sarcoma-associated herpesvirus ORF57
      mediated nuclear export of intronless viral mRNAs.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 plays a pivotal role in
      mediating the nuclear export of KSHV intronless transcripts. We demonstrate that
      ORF57 localises and dynamically trafficks through the nucleolus. To assess if
      nucleolar shuttling of ORF57 is important for the export of intronless viral
      mRNA, the ability of ORF57 to export mRNA was assessed in cells where the
      nucleolus was disrupted using Actinomycin D or DRB. We show that rapid
      disorganisation of the nucleolus was accompanied by a reduction in intronless
      virus mRNA export, suggesting that an intact nucleolus is essential for efficient
      KSHV ORF57-mediated intronless mRNA export.

PMID- 19850041
TI  - Inhibition of aldose reductase by dietary antioxidant curcumin: mechanism of
      inhibition, specificity and significance.
AB  - Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2)
      activity has been implicated in the development of various secondary
      complications of diabetes. In this study we show that curcumin inhibits ALR2 with
      an IC(50) of 10 microM in a non-competitive manner, but is a poor inhibitor of
      closely-related members of the aldo-keto reductase superfamily, particularly
      aldehyde reductase. Results from molecular docking studies are consistent with
      the pattern of inhibition of ALR2 by curcumin and its specificity. Moreover,
      curcumin is able to suppress sorbitol accumulation in human erythrocytes under
      high glucose conditions, demonstrating an in vivo potential of curcumin to
      prevent sorbitol accumulation. These results suggest that curcumin holds promise
      as an agent to prevent or treat diabetic complications.

PMID- 19850042
TI  - Correlation of mRNA and protein in complex biological samples.
AB  - The correlation between mRNA and protein abundances in the cell has been reported
      to be notoriously poor. Recent technological advances in the quantitative
      analysis of mRNA and protein species in complex samples allow the detailed
      analysis of this pathway at the center of biological systems. We give an overview
      of available methods for the identification and quantification of free and
      ribosome-bound mRNA, protein abundances and individual protein turnover rates. We
      review available literature on the correlation of mRNA and protein abundances and
      discuss biological and technical parameters influencing the correlation of these
      central biological molecules.

PMID- 19850044
TI  - Genomic analysis of a novel integrative conjugative element in Vibrio cholerae.
AB  - Integrative conjugative elements (ICEs) are a class of self-transmissible mobile
      elements that mediate horizontal gene transfer in bacteria, and play an important
      role in bacterial evolution. Since 1992, ICEs of the SXT/R391 family have been
      found to be widely distributed among Vibrio cholerae strains isolated in Asian
      countries. Here we describe ICEVchB33, an ICE found in the genomes of two V.
      cholerae O1 Eltor strains, one isolated in India, 1994, and the other from
      Mozambique, 2004. ICEVchB33 revealed a new genetic organization, different from
      other ICEs of the SXT/R391 family, demonstrating the genomic plasticity of these
      elements.

PMID- 19850043
TI  - PECAM-1 expression and activity negatively regulate multiple platelet signaling
      pathways.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits platelet
      response to collagen and may also inhibit two other major platelet agonists ADP
      and thrombin although this has been less well explored. We hypothesized that the
      combined effect of inhibiting these three platelet activating pathways may act to
      significantly inhibit thrombus formation. We demonstrate a negative relationship
      between PECAM-1 surface expression and platelet response to cross-linked collagen
      related peptide (CRP-XL) and ADP, and an inhibitory effect of PECAM-1 clustering
      on platelet response to CRP-XL, ADP and thrombin. This combined inhibition of
      multiple signaling pathways results in a marked reduction in thrombus formation.

PMID- 19850045
TI  - The histone demethylase RBP2 Is overexpressed in gastric cancer and its
      inhibition triggers senescence of cancer cells.
AB  - BACKGROUND & AIMS: The aberrant expression of histone-modifying enzymes such as
      histone deacetylases contributes to oncogenesis. It is unclear whether RBP2, a
      newly identified histone demethylase, is involved in cancer
      development/progression. We determined RBP2 expression in gastric cancer and its
      biologic function in cancer cells. METHODS: Cancerous and matched normal gastric
      specimens from 42 patients with gastric cancer were analyzed for RBP2 expression
      using quantitative real-time polymerase chain reaction and immunohistochemistry.
      Gene expression was assessed using quantitative real-time polymerase chain
      reaction and immunoblotting and depleted with small interference RNA.
      Clonogenesis and cellular senescence were examined by foci formation and beta
      Galactosidase staining. Promoter activity was determined by luciferase reporter
      assay. Chromatin immunoprecipitation was used to detect RBP2 and methylated
      histone H3-K4 on promoters. RESULTS: RBP2 messenger RNA and protein expression
      were increased in 71.5% (30/42) and 100% (20/20) of gastric cancer specimens,
      respectively. Significantly diminished foci numbers coupled with massive
      senescence/growth arrest and elevated expression of cyclin-dependent kinase
      inhibitors (CDKIs) p21(CIP1), p27(kip1), and/or p16(ink4a) occurred in RBP2
      depleted gastric and cervical cancer cells. RBP2 depletion-mediated senescence
      and clonogenic defect were attenuated by inhibiting p21(CIP1) or p27(kip1)
      expression. The promoter activity of all 3 CDKIs genes was enhanced by RBP2
      inhibition. RBP2 occupied these promoters in control cells, and the loss of RBP2
      occupancy was accompanied by enhanced H3-K4 trimethylation following RBP2
      depletion. CONCLUSIONS: RBP2 is overexpressed in gastric cancer, and its
      inhibition triggers senescence of malignant cells at least partially by
      derepressing its target genes CDKIs. Histone demethylase inhibition by targeting
      RBP2 may be an anticancer strategy.

PMID- 19850046
TI  - Parasites of three commercially exploited bivalve mollusc species of the
      estuarine region of the Cachoeira river (Ilheus, Bahia, Brazil).
AB  - This paper reports the parasites found in three commercially exploited bivalve
      molluscs (Mytella guyanensis, Anomalocardia brasiliana and Iphigenia brasiliana)
      of an estuarine region of Ilheus, south of Bahia, Brazil (14 degrees 48'23''S; 39
      degrees 02'47''W). Samples of 20 individuals of each species were collected
      fortnightly from August 2005 to August 2006. A total of 1480 individuals was
      collected and processed by standard histologic techniques; the histologic
      sections were stained with Harris haematoxylin and eosin and examined with light
      microscope. The water temperature in the study area varied from 24 to 30.5
      degrees C and the salinity from 0 to 23ppt. Remarkable differences were found in
      the parasitic community between the three mollusc species involved in the study,
      which occupied different habitats in the estuarine region of the Cachoeira river.
      The following parasites were found: intracellular rickettsia-like colonies in
      digestive epithelia; intracellular gregarine Nematopsis sp. in gills, mantle,
      gonad, digestive gland and foot muscle; sporocysts of a Bucephalidae trematode in
      gonads, mantle, gills, digestive gland and foot; unidentified digenetic
      metacercariae in digestive gland and gonad; metacestodes of Tylocephalum sp. in
      connective tissue in the digestive gland and in gonad; and an unidentified
      metazoan in mantle and intestinal lumen. No significant temporal variation in the
      prevalence of any parasite was detected, which could be due to the narrow
      temperature range of the region and the absence of patterns of salinity and
      rainfall variation through the year. The infestation by sporocyst was the only
      pathological threat detected for the studied populations because of its potential
      for host castration. The low infection intensity and/or prevalence of the other
      parasites and the lack of obvious lesions suggest that there is no other serious
      pathological risk for the studied mollusc populations.

PMID- 19850047
TI  - Genetic detection and quantification of Nosema apis and N. ceranae in the honey
      bee.
AB  - The incidence of nosemosis has increased in recent years due to an emerging
      infestation of Nosema ceranae in managed honey bee populations in much of the
      world. A real-time PCR assay was developed to facilitate detection and
      quantification of both Nosema apis and N. ceranae in both single bee and pooled
      samples. The assay is a multiplexed reaction in which both species are detected
      and quantified in a single reaction. The assay is highly sensitive and can detect
      single copies of the target sequence. Real-time PCR results were calibrated to
      spore counts generated by standard microscopy procedures. The assay was used to
      assess bees from commercial apiaries sampled in November 2008 and March 2009.
      Bees from each colony were pooled. A large amount of variation among colonies was
      evident, signifying the need to examine large numbers of colonies. Due to
      sampling constraints, a subset of colonies (from five apiaries) was sampled in
      both seasons. In November, N. apis levels were 1212+/-148 spores/bee and N.
      ceranae levels were 51,073+/-31,155 spores/bee. In March, no N. apis was
      detected, N. ceranae levels were 11,824+/-6304 spores/bee. Changes in N. ceranae
      levels were evident among apiaries, some increasing and other decreasing. This
      demonstrates the need for thorough sampling of apiaries and the need for a rapid
      test for both detection and quantification of both Nosema spp. This assay
      provides the opportunity for detailed study of disease resistance, infection
      kinetics, and improvement of disease management practices for honey bees.

PMID- 19850048
TI  - Activation of MTK1/MEKK4 induces cardiomyocyte death and heart failure.
AB  - MTK1 (MEKK4) is a mitogen-activated protein kinase kinase kinase that regulates
      the activity of its downstream mitogen-activated kinases, p38, and c-Jun N
      terminal kinase (JNK). However, the physiological function of MTK1 in the heart
      remains to be determined. Here, we attempted to elucidate the function of MTK1 in
      the heart using in vitro and in vivo models. MTK1 was activated in the hearts of
      mice subjected to pressure overload-induced heart failure. Overexpression of a
      constitutively active mutant of MTK1 (MTK1DeltaN) induced apoptosis in isolated
      neonatal rat cardiomyocytes, whereas a kinase domain-deleted form of MTK1
      attenuated H(2)O(2)-induced apoptosis. Specific inhibitors of p38 or JNK
      effectively protected cardiomyocytes from MTK1DeltaN-induced cell death. In mice,
      cardiac-specific overexpression of MTK1DeltaN resulted in early mortality
      compared with the lifespan of littermate controls. Echocardiographic analysis
      revealed increases in end-diastolic and end-systolic left ventricular internal
      dimensions and a decrease in fractional shortening in MTK1DeltaN transgenic mice.
      In addition, the mice showed characteristic phenotypes of heart failure such as
      an increase in lung weight. The number of TUNEL-positive myocytes and the level
      of cleaved caspase 3 protein were both increased in MTK1DeltaN transgenic mice.
      Thus, MTK1 plays an important role in the regulation of cell death and is also
      involved in the pathogenesis of heart failure.

PMID- 19850049
TI  - Analysis of angiogenesis induced by local IGF-1 expression after myocardial
      infarction using microSPECT-CT imaging.
AB  - Insulin-like growth factor-1 (IGF-1) has been found to exert favorable effects on
      angiogenesis in prior animal studies. This study explored the long-term effect of
      IGF-1 on angiogenesis using microSPECT-CT in infarcted rat hearts after
      delivering human IGF-1 gene by adeno-associated virus (AAV). Myocardial
      infarction (MI) was induced in Sprague-Dawley rats by ligation of the proximal
      anterior coronary artery and a total of 10(11) AAV-CMV-lacZ (control) or IGF-1
      vectors were injected around the peri-infarct area. IGF-1 expression by AAV
      stably transduced heart muscle for up to 16 weeks post-MI and
      immunohistochemistry revealed a remarkable increase in capillary density. A
      (99m)Tc-labeled RGD peptide (NC100692, GE Healthcare) was used to assess temporal
      and regional alpha(v) integrin activation. Rats were injected with NC100692
      followed by (201)Tl chloride and in vivo microSPECT-CT imaging was performed.
      After imaging, hearts were excised and cut for quantitative gamma-well counting
      (GWC). NC100692 retention was significantly increased in hypoperfused regions of
      both lacZ and IGF-1 rats at 4 and 16 weeks post-MI. Significantly higher
      activation of alpha(v) integrin was observed in IGF-1 rats at 4 weeks after
      treatment compared with control group, although the activation was lower in the
      IGF-1 group at 16 weeks. Local IGF-1 gene delivery by AAV can render a sustained
      transduction and improve cardiac function post-MI. IGF-1 expression contributes
      to enhanced alpha(v) integrin activation which is linked to angiogenesis.
      MicroSPECT-CT imaging with (99m)Tc-NC100692 and quantitative GWC successfully
      assessed differences in alpha(v) integrin activation between IGF-1-treated and
      control animals post-MI.

PMID- 19850050
TI  - Evolution of stability in a cold-active enzyme elicits specificity relaxation and
      highlights substrate-related effects on temperature adaptation.
AB  - Molecular aspects of thermal adaptation of proteins were studied by following the
      co-evolution of temperature dependence, conformational stability, and substrate
      specificity in a cold-active lipase modified via directed evolution. We found
      that the evolution of kinetic stability was accompanied by a relaxation in
      substrate specificity. Moreover, temperature dependence and selectivity turned
      out to be mutually dependent. While the wild-type protein was strictly specific
      for short-chain triglycerides (C4) in the temperature range 10-50 degrees C and
      displayed highest activity in the cold, its stabilized variant was able to accept
      C8 and C12 molecules and its selectivity was temperature dependent. We could not
      detect any improvement in the overall structural robustness of the mutant when
      the structure was challenged by temperature or chemical denaturants. There is,
      however, strong evidence for local stabilization effects in the active-site
      region provided by two independent approaches. Differential scanning fluorimetry
      revealed that the exposure of hydrophobic patches (as the active site is)
      precedes denaturation, and molecular dynamics simulations confirmed that
      stability was obtained by restriction of the mobility of the lid, a flexible
      structure that regulates the access to the enzyme active site and influences its
      stability. This reduction of lid movements is suggested to be accompanied by a
      concomitant increase in the mobility of other protein regions, thus accounting
      for the observed broadening of substrate specificity.

PMID- 19850051
TI  - The processing of human rhomboid intramembrane serine protease RHBDL2 is required
      for its proteolytic activity.
AB  - RHBDL2, a human homolog of the rhomboids, belongs to a unique class of serine
      intramembrane proteases; little is known about its function and regulation. Here,
      we show that RHBDL2 is produced as a proenzyme and that the processing of RHBDL2
      is required for its cellular protease activity. The processing of RHBDL2 was
      shown by both Western blot and immunofluorescence analysis. We have demonstrated
      that a highly conserved Arg residue on loop 1 of RHBDL2 plays a critical role in
      the activation of the proenzyme. The activation of RHBDL2 is catalyzed by a
      protease that is sensitive to a class of sulfonamide compounds. Furthermore,
      endogenous RHBDL2 exists as the processed form and treatment of cells with a
      sulfonamide inhibitor led to an accumulation of the full length of RHBDL2.
      Therefore, this study has demonstrated that RHBDL2 activity is regulated by
      proenzyme activation, revealed a role for the conserved WR residues in loop 1 in
      RHBDL2 activity, and provided critical insights into the regulation and function
      of this human rhomboid protease.

PMID- 19850052
TI  - Sequence-dependent DNA flexibility mediates DNase I cleavage.
AB  - Understanding the preference of nonspecific proteins for certain DNA structural
      features requires an accurate description of the properties of free DNA,
      especially regarding their possible predisposition to adopt a conformation that
      favors the formation of a complex. Exploiting previous exhaustive NMR studies
      performed on free DNA oligomers, we investigated the molecular basis of DNase I
      sensitivity under conditions where DNase I binding limits the probability of
      cleavage. We showed that cleavage intensity was correlated with adjacent 3'
      phosphate linkage flexibility, monitored by (31)P chemical shifts. Examining NMR
      refined DNA structures highlighted that sequence-dependent flexible phosphates
      were associated with large minor groove variations that may promote the affinity
      of DNase I, according to relevant DNA-protein complexes. In sum, this work
      demonstrates that specificity in DNA-DNase I interaction is mediated by DNA
      flexibility, which influences the induced-fit transitions required to form
      productive complexes.

PMID- 19850053
TI  - Conformational flexibility and peptide interaction of the translocation ATPase
      SecA.
AB  - The SecA ATPase forms a functional complex with the protein-conducting SecY
      channel to translocate polypeptides across the bacterial cell membrane. SecA
      recognizes the translocation substrate and catalyzes its unidirectional movement
      through the SecY channel. The recent crystal structure of the Thermotoga maritima
      SecA-SecYEG complex shows the ATPase in a conformation where the nucleotide
      binding domains (NBDs) have closed around a bound ADP-BeFx complex and SecA's
      polypeptide-binding clamp is shut. Here, we present the crystal structure of T.
      maritima SecA in isolation, determined in its ADP-bound form at 3.1 A resolution.
      SecA alone has a drastically different conformation in which the nucleotide
      binding pocket between NBD1 and NBD2 is open and the preprotein cross-linking
      domain has rotated away from both NBDs, thereby opening the polypeptide-binding
      clamp. To investigate how this clamp binds polypeptide substrates, we also
      determined a structure of Bacillus subtilis SecA in complex with a peptide at 2.5
      A resolution. This structure shows that the peptide augments the highly conserved
      beta-sheet at the back of the clamp. Taken together, these structures suggest a
      mechanism by which ATP hydrolysis can lead to polypeptide translocation.

PMID- 19850054
TI  - Semaphorin 5A promotes angiogenesis by increasing endothelial cell proliferation,
      migration, and decreasing apoptosis.
AB  - Semaphorin 5A (mouse, Sema5A; human, SEMA5A), is an axon regulator molecule and
      plays major roles during neuronal and vascular development. The importance of
      Sema5A during vasculogenesis, however, is unclear. The fact that Sema5A deficient
      mice display a defective branching of cranial vasculature supports its
      participation in blood vessel formation. In this study, we tested our hypothesis
      that Sema5A regulates angiogenesis by modulating various steps during
      angiogenesis. Accordingly, we demonstrated that the treatment of immortalized
      endothelial cells with recombinant extracellular domain of mouse Sema5A
      significantly increased endothelial cell proliferation and migration and
      decreased apoptosis. We also observed a relative increase of endothelial
      expression of anti-apoptotic genes relative to pro-apoptotic genes in Sema5A
      treated endothelial cells suggesting its role in inhibition of apoptosis. In
      addition, our data suggest that Sema5A decreases apoptosis through activation of
      Akt, increases migration through activating Met tyrosine kinases and
      extracellular matrix degradation through matrix metalloproteinase 9. Moreover, in
      vivo Matrigel plug assays demonstrated that Sema5A induces endothelial cell
      migration from pre-existing vessels. In conclusion, the present work shows the
      pro-angiogenic role of Sema5A and provides clues on the signaling pathways that
      underlie them.

PMID- 19850055
TI  - Greater superior than inferior parietal lobule activation with increasing
      rotation angle during mental rotation: an fMRI study.
AB  - Mental rotation is a task known to activate the parietal cortical regions. The
      present study aimed to investigate whether there is differential activation of
      regions within the parietal lobe and to reveal functional subspecialisation of
      this region by examining the effects of increasing angle of rotation. Functional
      magnetic resonance imaging was performed in nine healthy female subjects whilst
      undertaking a parametric mental rotation task. The task comprised 6 alphanumeric
      characters presented in their normal or mirror-reversed orientation.
      Behaviourally, subjects showed increased reaction times with increased angle of
      rotation, with differential effects between the alphanumeric characters; numbers
      having greater reaction times than letters. BOLD signal increase was observed
      bilaterally in the middle occipital gyrus and medial frontal gyrus, in the right
      superior and inferior parietal lobules and in the left superior temporal gyrus.
      Parametric increases in activation with increasing angle of rotation were
      observed bilaterally in the superior and inferior parietal lobules and in the
      right medial frontal gyrus, with greater parametric effects in the superior
      parietal lobules compared to the inferior parietal lobules. Our findings suggest
      subspecialisation of the posterior parietal lobules during mental rotation, with
      differential responses in the superior and inferior regions.

PMID- 19850057
TI  - Spatially explicit neutral models for population genetics and community ecology:
      Extensions of the Neyman-Scott clustering process.
AB  - Spatially explicit models relating to plant populations have developed little
      since Felsenstein (1975) pointed out that if limited seed dispersal causes
      clustering of individuals, such models cannot reach an equilibrium. This paper
      aims to resolve this issue by modifying the Neyman-Scott cluster point process.
      The new point processes are dynamic models with random immigration, and the
      continuous increase in the clustering of individuals stops at some level. Hence,
      an equilibrium state is achieved, and new individual-based spatially explicit
      neutral coalescent models are established. By fitting the spatial structure at
      equilibrium to individual spatial distribution data, we can indirectly estimate
      seed dispersal and effective population density. These estimates are improved
      when genetic data are available, and become even more sophisticated if spatial
      distribution and genetic data pertaining to the offspring are also available.

PMID- 19850056
TI  - Anhedonia in postpartum rats.
AB  - Postpartum depression (PPD) is a debilitating illness, yet little is known about
      its causes. The purpose of this study was to examine a major symptom of
      depression during the postpartum period, anhedonia, by comparing sucrose
      preference in female rats that had undergone actual pregnancy or hormone
      simulated pregnancy (HSP) to their respective controls. Whereas HSP rats showed
      significantly less preference than vehicle control rats for 1% sucrose solution
      during the first three weeks of the "postpartum" period, previously pregnant
      females showed only slightly depressed sucrose preference for the first 1-2 days
      postpartum, compared to non-pregnant controls. Habituation to 1% sucrose during
      the pregnancy period, which increased preference upon later testing in previously
      pregnant rats tested on postpartum day 2, did not significantly increase
      preference in HSP rats, suggesting that depressed preference in the latter group
      was not due to neophobia. Pre-treatment with desipramine did not prevent
      suppressed sucrose preference in HSP rats, and preference was even further
      suppressed following chronic sertraline treatment. These results suggest that
      estradiol withdrawal following HSP may cause anhedonia during the early
      "postpartum" period. In contrast, females that have undergone actual pregnancy
      are less likely to show this effect, suggesting that postpartum hormonal changes
      other than the dramatic decline in estradiol may buffer its negative mood
      effects.

PMID- 19850058
TI  - Secondhand tobacco smoke exposure differentially alters nucleus tractus
      solitarius neurons at two different ages in developing non-human primates.
AB  - Exposing children to secondhand tobacco smoke (SHS) is associated with increased
      risk for asthma, bronchiolitis and SIDS. The role for changes in the developing
      CNS contributing to these problems has not been fully explored. We used rhesus
      macaques to test the hypothesis that SHS exposure during development triggers
      neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory
      information related to changes in airway and lung function is first integrated.
      Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5
      days/week starting at 50-day gestational age. Mother/infant pairs continued the
      exposures postnatally to age 3 or 13 months, which may be equivalent to
      approximately 1 or 4 years of human age, respectively. Whole-cell recordings were
      made of second-order NTS neurons in transverse brainstem slices. To target the
      consequences of SHS exposure based on neuronal subgroups, we classified NTS
      neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking
      (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed
      animals. RS neurons showed greater cell excitability especially at age of 3
      months while DS neurons received greater amplitudes of excitatory postsynaptic
      currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic
      and synaptic excitabilities were detected especially in DS neurons. In 3 month
      olds, SHS exposure effects were limited to excitatory changes in RS neurons,
      specifically increases in evoked EPSC amplitudes and increased spiking responses
      accompanied by shortened action potential width. By 13 months, the continued SHS
      exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and
      blunted spiking responses accompanied by prolonged action potential width. The
      influence of SHS exposure on age-related and phenotype specific changes may be
      associated with age-specific respiratory problems, for which SHS exposure can
      increase the risk, such as SIDS and bronchiolitis in infants and asthma in older
      children.

PMID- 19850059
TI  - Glutathione-S-transferase A3 knockout mice are sensitive to acute cytotoxic and
      genotoxic effects of aflatoxin B1.
AB  - Aflatoxin B1 (AFB1) is a major risk factor for hepatocellular carcinoma (HCC) in
      humans. However, mice, a major animal model for the study of AFB1 carcinogenesis,
      are resistant, due to high constitutive expression, in the mouse liver, of
      glutathione S-transferase A3 subunit (mGSTA3) that is lacking in humans. Our
      objective was to establish that a mouse model for AFB1 toxicity could be used to
      study mechanisms of toxicity that are relevant for human disease, i.e., an mGSTA3
      knockout (KO) mouse that responds to toxicants such as AFB1 in a manner similar
      to humans. Exons 3-6 of the mGSTA3 were replaced with a neomycin cassette by
      homologous recombination. Southern blotting, RT-PCR, Western blotting, and
      measurement of AFB1-N(7)-DNA adduct formation were used to evaluate the mGSTA3 KO
      mice. The KO mice have deletion of exons 3-6 of the mGSTA3 gene, as expected, as
      well as a lack of mGSTA3 expression at the mRNA and protein levels. Three hours
      after injection of 5 mg/kg AFB1, mGSTA3 KO mice have more than 100-fold more AFB1
      N(7)-DNA adducts in their livers than do similarly treated wild-type (WT) mice.
      In addition, the mGSTA3 KO mice die of massive hepatic necrosis, at AFB1 doses
      that have minimal toxic effects in WT mice. We conclude that mGSTA3 KO mice are
      sensitive to the acute cytotoxic and genotoxic effects of AFB1, confirming the
      crucial role of GSTA3 subunit in protection of normal mice against AFB1 toxicity.
      We propose the mGSTA3 KO mouse as a useful model with which to study the
      interplay of risk factors leading to HCC development in humans, as well as for
      testing of additional possible functions of mGSTA3.

PMID- 19850060
TI  - Potent homocysteine-induced ERK phosphorylation in cultured neurons depends on
      self-sensitization via system Xc(-).
AB  - Homocysteine is increased during pathological conditions, endangering vascular
      and cognitive functions, and elevated homocysteine during pregnancy may be
      correlated with an increased incidence of schizophrenia in the offspring. This
      study showed that millimolar homocysteine concentrations in saline medium cause
      phosphorylation of extracellular-signal regulated kinases 1 and 2 (ERK(1/2)) in
      cerebellar granule neurons, inhibitable by metabotropic but not ionotropic
      glutamate receptor antagonists. These findings are analogous to observations by
      Zieminska et al. (2003), that similar concentrations cause neuronal death.
      However, these concentrations are much higher than those occurring clinically
      during hyperhomocysteinemia. It is therefore important that a approximately 10
      fold increase in potency occurred in the presence of the glutamate precursor
      glutamine, when ERK(1/2) phosphorylation became inhibitable by NMDA or non-NMDA
      antagonists and dependent upon epidermal growth factor (EGF) receptor
      transactivation. However, glutamate release to the medium was reduced, suggesting
      that reversal of the cystine/glutamate antiporter, system X(c)(-) could be
      involved in potentiation of the response by causing a localized release of
      initially accumulated homocysteine. In agreement with this hypothesis further
      enhancement of ERK(1/2) phosphorylation occurred in the additional presence of
      cystine. Pharmacological inhibition of system X(c)(-) prevented the effect of
      micromolar homocysteine concentrations, and U0126-mediated inhibition of ERK(1/2)
      phosphorylation enhanced homocysteine-induced death. In conclusion, homocysteine
      interacts with system X(c)(-) like quisqualate (Venkatraman et al. 1994), by
      "self-sensitization" with initial accumulation and subsequent release in exchange
      with cystine and/or glutamate, establishing high local homocysteine
      concentrations, which activate adjacent ionotropic glutamate receptors and cause
      neurotoxicity.

PMID- 19850062
TI  - DMI-induced sexual effects in male rats: analysis of DMI's acute and chronic
      actions on copulatory behavior and on the genital motor pattern of ejaculation.
AB  - Desipramine (DMI) is a tricyclic antidepressant that alters male sexual function.
      This work was designed to study the effects of acute and chronic DMI treatments
      on male rat copulatory behavior, discriminating between spinal and behavioral DMI
      actions on the ejaculatory response. To this aim, sexually experienced male
      Wistar rats received DMI (7.5 or 15 mg/kg, i.p.) for 14 days and were tested for
      sexual behavior on Days 1, 7 and 14 of treatment. Besides, the genital motor
      pattern of ejaculation (GMPE) was recorded in anaesthetized, spinal male rats
      after acute (1-10 microg, i.v.) or 14-day chronic DMI (15 mg/kg, i.p.) treatment.
      Results showed that acute and chronic DMI treatments reduced the ejaculatory
      threshold by decreasing intromission number and ejaculation latency of male rats,
      in successive copulatory series. The intensity of the effects depended on the
      dose and treatment duration. DMI acute treatment activated GMPE expression only
      at the lower doses and these responses exhibited modified parameters. Chronic DMI
      reduced the number of discharges and increased the frequency of discharge of
      spontaneous GMPE responses, affected mechanically evoked ones and increased the
      number of GMPEs expressed after repeated genital stimulation as compared to
      control rats. DMI treatments affected copulatory behavior both at brain and
      spinal levels and its effects on ejaculation, assumed to be similar in behavioral
      and spinal models, differed.

PMID- 19850061
TI  - The influence of intrinsically-photosensitive retinal ganglion cells on the
      spectral sensitivity and response dynamics of the human pupillary light reflex.
AB  - Historically, it was assumed that the light-evoked neural signals driving the
      human pupillary light reflex (PLR) originated exclusively from rod and cone
      photoreceptors. However, a novel melanopsin-containing photoreceptive cell class
      has recently been discovered in the mammalian retina. These intrinsically
      photosensitive retinal ganglion cells (ipRGCs) project to the pretectum, the
      retinorecipient area of the brain responsible for the PLR. This study was
      therefore designed to examine the relative contribution of rod, cone and the
      melanopsin photoresponses of ipRGCs to the human PLR. We establish that the
      melanopsin photoresponse of ipRGCs contributes significantly to the maintenance
      of half maximal pupilloconstriction in response to light stimuli of 30s or
      longer, even at low photopic irradiances. Furthermore, we show that the
      melanopsin photoresponse contributes significantly to three-quarter maximal
      pupilloconstriction in response to light stimuli as short as 2s. We also
      demonstrate that cone photoresponses driving pupilloconstriction adapt
      considerably and contribute little after 30s, but rod photoresponses adapt less
      and contribute significantly to the maintenance of pupilloconstriction in
      response to steady-state light stimuli at irradiance levels which are below the
      threshold of the melanopsin photoresponse.

PMID- 19850063
TI  - Using the theory of planned behavior to examine effectiveness of an educational
      intervention on infant feeding in China.
AB  - OBJECTIVE: To determine the effectiveness of an educational intervention on
      infant feeding behaviors and mothers' psychosocial mediating variables based on
      the Theory of Planned Behavior (TPB), and to assess the predictive effect of
      mediating variables on mothers' intention and feeding practices. METHODS: We did
      a cluster-randomized trial in 8 paired townships of Laishui County, China during
      2006-2007. 599 mothers with infants aged 2-4-mo were enrolled at the baseline
      survey, of whom 485 were followed up after 11-mo intervention. RESULTS: The
      intervention group had significantly higher scores than controls in knowledge,
      attitudes, self-efficacy, intention, norm beliefs, as well as feeding behaviors
      (Hotellings T-square=143.96, P<0.01). Mothers' intention towards recommended
      feeding behaviors was positively associated with mothers' attitudes, subjective
      norms and self-efficacy at baseline, and was associated with their attitudes,
      self-efficacy, and knowledge at post-intervention evaluation. Intervention,
      mothers' knowledge, intention and subjective norm of villagers were independent
      predictors of their feeding behaviors after intervention. CONCLUSIONS: Findings
      from this study suggested that TPB is an appropriate theory for explaining the
      effect of psychosocial factors such as knowledge, attitudes, self-efficacy,
      subjective norms, and intentions on infant feeding behaviors, and a useful
      guideline to design the targets and key approaches for infant feeding
      interventions.

PMID- 19850064
TI  - Exploring the relationship between race/ethnicity, menthol smoking, and
      cessation, in a nationally representative sample of adults.
AB  - OBJECTIVE: To explore the relationship between race/ethnicity, menthol smoking,
      and cessation in a nationally representative sample of adults. METHODS: Data from
      the 2005 U.S. National Health Interview Survey was analyzed. Our analyses were
      restricted to 7815 white, black, and Hispanic current and former cigarette
      smokers who indicated that they do not currently use other tobacco products and
      have made a quit attempt. We used multiple logistic regressions to test the
      relationship of menthol smoking and cessation controlling for various factors.
      RESULTS: Significant interaction effects were found indicating that the
      association between menthol smoking and cessation differs between whites and
      blacks, and whites and Hispanics. When blacks and Hispanics are collapsed as non
      white, we found that non-white menthol smokers were significantly less likely to
      have quit smoking (adjusted odds ratio=0.55, p<0.01) compared to their non
      menthol smoking counterparts. In contrast, among whites, menthol smokers were
      more likely to be former smokers than nonmenthol smokers (adjusted odds
      ratio=1.17, p<0.05). CONCLUSION: Our findings provide some support for the
      hypothesis that menthol smoking can lead to poorer cessation outcomes, but only
      for non-white smokers.

PMID- 19850065
TI  - Healthy & Active Communities Initiative: a foundation's response to the obesity
      epidemic.
AB  - Missouri has the 12th highest rate of adult obesity and the 15th highest rate of
      overweight and obese youth in the United States. In response, Missouri Foundation
      for Health has implemented the Healthy and Active Communities Initiative (H&AC).
      Methods applied through H&AC include grantmaking, evaluation support,
      dissemination technical assistance, policy assessment, and development of local,
      regional, and statewide collaborations to increase access to physical activity
      and nutrition through environmental, policy and behavior change. Results to date
      demonstrate more than 49 counties in the state have been impacted through 79
      grantee projects. Nearly half (45%) of these grantees have achieved more than
      their original goals and 60% of grantees can sustain at least half of their
      program activities post award. Fifty percent of grantees have helped to change
      the way the community works on public issues. Through the H&AC Initiative,
      Missouri Foundation for Health serves as a model for how a foundation can assist
      in efforts to mitigate and prevent rising rates of obesity.

PMID- 19850066
TI  - Correlation between physical activity and self-rated health status of non-elderly
      adults with disabilities.
AB  - OBJECTIVES: Physical activity participation is a promising pathway for reducing
      chronic disease risk and improving health outcomes of adults with disabilities.
      The objective of this study was to examine physical activity participation as a
      potential predictor of self-rated health status of a unique sub-population of non
      elderly, non-assistive device using adults with disabilities. METHODS: This cross
      sectional study analyzed population-based data from the 2007 U.S. Behavioral Risk
      Factor Surveillance System. A sample of 46,883 adults with disabilities was
      examined. Multivariable logistic regression analyses were conducted to determine
      whether physical activity participation predicted self-rated health status
      controlling for age, gender, income level, health insurance status, BMI, smoking
      status, education level, and heart disease, arthritis, asthma and diabetes
      diagnoses. RESULTS: Physical activity participation was significantly associated
      with self-rated health status. Those who participated in no physical activity
      were more likely to report fair or poor health by a factor of 3.3 (95% CI: 2.6
      4.2) compared to those who met national recommendations for physical activity.
      Only 43.1% met one or both of the recommended physical activity guidelines.
      CONCLUSIONS: Adequate physical activity participation is correlated to better
      health status among adults with disabilities not associated with aging. Physical
      activity promotion is warranted for this population.

PMID- 19850067
TI  - Parks and physical activity: why are some parks used more than others?
AB  - OBJECTIVE: To assess how park characteristics and demographic factors are
      associated with park use. METHODS: We studied a diverse sample of parks in a
      Southern California metropolitan area in 2006-2008 representing a variety of
      racial and ethnic communities of different socioeconomic strata. We surveyed 51
      park directors, 4257 park users and local residents, and observed 30 parks. We
      explored relationships among the number of people observed, the number of park
      programs offered, number of organized activities observed, park size, existence
      of park advisory board, perceptions of safety, and population density and
      characteristics. RESULTS: The strongest correlates of the number of people using
      the park were the park size and the number of organized activities observed.
      Neighborhood population density, neighborhood poverty levels, perceptions of park
      safety, and the presence of a park advisory board were not associated with park
      use. CONCLUSION: While perceptions of low safety have been considered a barrier
      to park use, perceptions of high safety do not appear to facilitate park use.
      Having events at the park, including sports competitions and other attractions,
      appears to be the strongest correlate of park use and community-level physical
      activity.

PMID- 19850069
TI  - Active communities for youth and families: using research to create momentum for
      change.

PMID- 19850068
TI  - Automobile traffic around the home and attained body mass index: a longitudinal
      cohort study of children aged 10-18 years.
AB  - OBJECTIVES: The objective of this study is to examine the relationship between
      measured traffic density near the homes of children and attained body mass index
      (BMI) over an eight-year follow up. METHODS: Children aged 9-10 years were
      enrolled across multiple communities in Southern California in 1993 and 1996
      (n=3318). Children were followed until age 18 or high school graduation to
      collect longitudinal information, including annual height and weight
      measurements. Multilevel growth curve models were used to assess the association
      between BMI levels at age 18 and traffic around the home. RESULTS: For traffic
      within 150 m around the child's home, there were significant positive
      associations with attained BMI for both sexes at age 18. With the 300 m traffic
      buffer, associations for both male and female growth in BMI were positive, but
      significantly elevated only in females. These associations persisted even after
      controlling for numerous potential confounding variables. CONCLUSIONS: This
      analysis yields the first evidence of significant effects from traffic density on
      BMI levels at age 18 in a large cohort of children. Traffic is a pervasive
      exposure in most cities, and our results identify traffic as a major risk factor
      for the development of obesity in children.

PMID- 19850070
TI  - The increased incidence of obstetric anal sphincter rupture--an emerging trend in
      Finland.
AB  - OBJECTIVE: To describe recent trends in the prevalence and risk factors of
      obstetric anal sphincter ruptures during between 1997 and 2007 in Finland.
      METHOD: We analyzed a population-based register of 514,741 women with singleton
      vaginal deliveries recorded in the Finnish Medical Birth Register. Primiparous
      (n=2315) and multiparous women (n=534) with anal rupture compared in terms of
      possible risk factors to primiparous (n=215,463) and multiparous (n=296,429)
      women without anal rupture, respectively, using stepwise logistic regression
      analysis. RESULTS: The occurrence of anal rupture increased from 0.5% in 1997
      1999 to 1.8% in 2006-2007 among primiparous women, and from 0.1% in 1997-2001 to
      0.3% in 2006-2007 among multiparous women. Over the study period, the likelihood
      of women having anal rupture in these groups increased by a factor of 3.28 (95%
      CI 2.86-3.76) and 2.83 (95% CI 2.19-3.67), respectively, after adjustments for
      strong associations with many known risks. Changes in population characteristics
      and in the use of interventions were small, and these did not cause the increased
      anal rupture rate. The only exception was vacuum-assisted deliveries, which
      explained about 9% of the rising anal rupture risk. CONCLUSIONS: The current
      obstetric practice is not optimal for protecting the perineum and reflects the
      need to standardise obstetric care.

PMID- 19850071
TI  - Carbonless footprints: promoting health and climate stabilization through active
      transportation.
AB  - OBJECTIVE: Our objective was to describe how active transportation can help meet
      health and greenhouse gas emissions goals, and the ability of urban form
      strategies to impact both issues. In addition, we wanted to assess if there is an
      inverse relationship between active and motorized forms of travel. METHODS: A
      cross-sectional analysis of travel diary data was used to measure relationships
      among energy (kcal) burned from walking, energy (kcal) burned from motorized
      transportation, and the ratio of the two (the transport energy index) with
      regional accessibility and local walkability when adjusting for demographic
      factors. Multiple linear regression and descriptive statistics were employed to
      estimate these relationships. RESULTS: Transit accessibility, residential
      density, and intersection density were positive predictors of walk energy and the
      energy index and inverse predictors of motorized energy. The land use mix
      variable was negatively and significantly associated with energy burned from
      walking and from motorized transportation, with no significant impact on the
      transport energy index. Because a mixed land use pattern places destinations
      closer together, it reduces distances and thus energy demands for both walking
      and driving. CONCLUSIONS: The results support the concept, previously untested
      empirically, that similar urban form strategies can have cobenefits for both
      physical activity and climate change.

PMID- 19850072
TI  - Are secondary data sources on the neighbourhood food environment accurate? Case
      study in Glasgow, UK.
AB  - OBJECTIVES: To assess the validity of a publicly available list of food stores
      through field observations of their existence, in order to contribute to research
      on neighbourhood food environments and health. METHODS: All multiple-owned
      supermarkets, and a 1 in 8 sample of other food outlets, listed in 1997 and 2007
      in the public register of food premises held by Glasgow City Council, Scotland,
      were visited to establish whether they were trading as foodstores. Postcode
      sectors in which foodstores were located were classified into least, middling and
      most deprived neighbourhoods. RESULTS: In total, 325 listed foodstores were
      visited in 1997 and 508 in 2007. Of these 87% and 88%, respectively, were trading
      as foodstores. There was a very slight gradient in validity by deprivation, with
      validity higher in least deprived neighbourhoods, though this was not
      statistically significant. CONCLUSIONS: There was reasonable, but not perfect,
      agreement between the list of food premises and field observations, with nearly 1
      in 9 of sampled foodstores not present on the ground. Since the use of inaccurate
      secondary data sources may affect estimates of relationships between the
      neighbourhood food environment and health, further work is required to establish
      the validity of such data in different contexts.

PMID- 19850073
TI  - Factors associated with short and long sleep.
AB  - OBJECTIVE: Short (<7 h) and long sleep durations (> or = 9 h) have recently been
      linked with increased mortality in the US, Europe and Asia, but little is known
      about the sleep patterns of Australian adults. The present study examined the
      sleep habits of Australian adults and identified socio-demographic and health
      related factors associated with short and long sleep. METHODS: This study
      analyzed cross-sectional and self-reported data from 49,405 Australian adults
      aged 45 to 65 years collected between 2006 and 2008. Socio-demographic and health
      related factors were entered into multinomial logistic regression models
      predicting self-reported sleep duration. RESULTS: Short and long sleep were
      reported by 16.6% and 13.9% of participants respectively. Short sleep was
      associated with long working hours (odds ratio [OR]=1.17, 95% confidence interval
      (CI): 1.08, 1.28) and obesity (OR=1.29, 95% CI: 1.19, 1.41); long sleep was
      associated with recent treatment for cancer (OR=1.64, 95% CI: 1.34, 2.02) and
      heart attack/angina (OR=1.58, 95% CI: 1.19, 2.09). CONCLUSIONS: Short and long
      sleep were common in this sample of middle aged Australian adults. The
      determinants of short sleep have potential public health implications and could
      be targeted to prevent morbidity and mortality associated with short sleep.

PMID- 19850074
TI  - Facility provision in elementary schools: correlates with physical education,
      recess, and obesity.
AB  - OBJECTIVES: The objectives were to: (1) document correlations among facility
      provision (availability and adequacy) in elementary schools, child
      sociodemographic factors, and school characteristics nationwide; and (2)
      investigate whether facility provision is associated with physical education (PE)
      time, recess time, and obesity trajectory. METHODS: The analytic sample included
      8935 fifth graders from the Early Childhood Longitudinal Survey Kindergarten
      Cohort. School teachers and administrators were surveyed about facility
      provision, PE, and recess time in April 2004. Multivariate linear and logistic
      regressions that accounted for the nesting of children within schools were used.
      RESULTS: Children from disadvantaged backgrounds were more likely to attend a
      school with worse gymnasium and playground provision. Gymnasium availability was
      associated with an additional 8.3 min overall and at least an additional 25 min
      of PE per week for schools in humid climate zones. These figures represent 10.8
      and 32.5%, respectively, of the average time spent in PE. No significant findings
      were obtained for gymnasium and playground adequacy in relation to PE and recess
      time, and facility provision in relation to obesity trajectory. CONCLUSIONS: Poor
      facility provision is a potential barrier for school physical activity programs
      and facility provision is lower in schools that most need them: urban, high
      minority, and high enrollment schools.

PMID- 19850075
TI  - Molecular cloning and functional characterization of porcine DNA-dependent
      activator of IFN-regulatory factors (DAI).
AB  - The DNA-dependent activator of IFN-regulatory factors (DAI) is a recently
      identified DNA sensor for intracellular DNA that triggers a signal for the
      production of type I IFN. Here we report the cloning and characterization of
      porcine DAI (poDAI). The full-length of poDAI encodes 439 amino acids, contains
      two N-terminal DNA-binding domains and shows similarity to mouse, rat, dog,
      monkey, human, horse and cattle counterparts ranging from 44% to 67%. poDAI mRNA
      expression was mainly detected in spleen, lung, kidney and small intestine. Over
      expression of poDAI activated transcription factors IRF3 and NF-kappaB and
      induced IFN-beta in different porcine cell lines, but to varying degrees.
      Deletion mutant analysis revealed that both the DNA-binding domains and the C
      terminus are required for full activation of IFN-beta. siRNA targeting poDAI
      significantly decreased poly(dAT:dAT)- or Pseudorabies virus (PRV)-induced IFN
      beta activation. These results indicate that DAI is an important immuno-regulator
      of the porcine innate immune system.

PMID- 19850076
TI  - First report of linear megaplasmids in the genus Micrococcus.
AB  - High-altitude wetlands (above 4200m) in the northwest of Argentina are considered
      pristine and extreme environments. Micrococcus sp. A1, H5, and V7, isolated from
      such environments, were shown to contain linear megaplasmids, designated pLMA1,
      pLMH5, and pLMV7, respectively. As known from linear plasmids of other
      actinomycetes, all three plasmids were resistant to lambda exonuclease treatment,
      which is consistent with having terminal proteins covalently attached to their 5'
      DNA ends. Electrophoretic mobility, Southern analysis, and restriction
      endonuclease patterns revealed pLMA1 and pLMH5 being indistinguishable plasmids,
      even though they were found in different strains isolated from two distant
      wetlands - Laguna Azul and Laguna Huaca Huasi. Analysis of 16S rDNA sequences of
      Micrococcus sp. A1, H5, and V7 suggested a close relationship to Micrococcus
      luteus. Typing of isolates was performed using fingerprint patterns generated by
      BOX-PCR. Plasmid-deficient strains, generated from Micrococcus sp. A1, showed a
      significantly decreased resistance level for erythromycin.

PMID- 19850079
TI  - Adeno-associated viral vector (AAV)-mediated gene transfer in the red nucleus of
      the adult rat brain: comparative analysis of the transduction properties of seven
      AAV serotypes and lentiviral vectors.
AB  - Recombinant adeno-associated viral vectors (AAVs) are very promising gene
      transfer tools for the nervous system. We have compared the efficiency of gene
      expression of seven AAV serotypes in young adult rats following a single
      injection in a major nucleus of the mid brain, the red nucleus, which is the
      origin of the rubrospinal tract. AAV serotypes 1-6 and 8 and a lentiviral vector
      (LV) were used, all encoding green fluorescent protein (GFP) under control of the
      cytomegalovirus (CMV) promoter. AAV vectors were titer matched at 5x10(11)
      genomic copies (GC)/ml and 1mul was injected into the red nucleus. The proportion
      of transduced neurons in the red nucleus was determined at 1 and 4 weeks post
      injection. AAV1 would be the vector of choice if the aim would be to overexpress
      a transgene at high level for a longer period of time. AAV5 and AAV8 would be the
      preferred serotype if onset of expression is should be somewhat delayed. The use
      of lentiviral vectors should be considered when transduction of both glial cells
      and neurons is required. Serotypes 3 and 4 did not transduce red nucleus neurons.
      AAV1, AAV6 and LV would be the vectors of choice if the aim of the experiment
      would be to rapidly express a transgene. The current data are important for the
      design of experiments that aim to study the effects of transgene products on the
      regenerative capacity of injured red nucleus neurons.

PMID- 19850077
TI  - Motor control and aging: links to age-related brain structural, functional, and
      biochemical effects.
AB  - Although connections between cognitive deficits and age-associated brain
      differences have been elucidated, relationships with motor performance are less
      well understood. Here, we broadly review age-related brain differences and motor
      deficits in older adults in addition to cognition-action theories. Age-related
      atrophy of the motor cortical regions and corpus callosum may precipitate or
      coincide with motor declines such as balance and gait deficits, coordination
      deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter
      systems-primarily the dopaminergic system-may contribute to age-related gross and
      fine motor declines, as well as to higher cognitive deficits. In general, older
      adults exhibit involvement of more widespread brain regions for motor control
      than young adults, particularly the prefrontal cortex and basal ganglia networks.
      Unfortunately these same regions are the most vulnerable to age-related effects,
      resulting in an imbalance of "supply and demand". Existing exercise,
      pharmaceutical, and motor training interventions may ameliorate motor deficits in
      older adults.

PMID- 19850078
TI  - Real-time glutamate measurements in the putamen of awake rhesus monkeys using an
      enzyme-based human microelectrode array prototype.
AB  - Commonly used for research studies in the central nervous system, microdialysis
      has revealed a link between dysregulation of the excitatory neurotransmitter
      glutamate and ischemia and seizure, however limitations like slow temporal
      resolution have stalled the advancement of microdialysis as a diagnostic tool. We
      have developed and extensively characterized an enzyme-based microelectrode array
      technology for second-by-second in vivo amperometric measurements of glutamate in
      the mammalian CNS. The current studies demonstrated the ability of a human
      microelectrode array prototype (Spencer-Gerhardt-2 (SG-2)) to measure tonic and
      phasic glutamate neurotransmission in the putamen of unanesthetized non-human
      primates. We also showed that the SG-2 remains functional following
      sterilization. Ability to monitor dynamic changes in glutamate in real-time may
      assist the development of clinical algorithms to potentially alert care-providers
      prior to onset of overt ischemia or seizure, or provide neurosurgeons with second
      by-second measurements of rapid changes in extracellular glutamate which could
      help guide surgical procedures or aid in interventional strategies.

PMID- 19850080
TI  - A semi-correlative technique for the subcellular localization of proteins in
      Drosophila synapses.
AB  - The neuromuscular junction (NMJ) in Drosophila larvae serves as an important
      model system to study synaptic vesicle recycling, plasticity, development, and
      organelle trafficking in nerve terminals. Here we provide a protocol that
      reliably localizes proteins subcellularly in this system in combination with good
      preservation of the ultrastructure of the NMJ. In this protocol, the NMJs are cut
      open to increase access of reagents to the interior of the synapse, stained with
      primary antibodies followed by secondary antibodies conjugated to Fluoronanogold
      particles to allow selection of the best-stained areas for electron microscopic
      (EM) analysis using confocal microscopy. To improve visualization at the EM
      level, the nanogold particles are silver enhanced. Good penetration of the
      antibodies in this protocol allows for a three-dimensional reconstruction of the
      labeling pattern from serial ultrathin sections. To explore the utility and
      resolution of this approach, we determined the ultrasturcutral localization of
      the cell adhesion molecule Fascicline II (Fas II) at rest using an antibody
      raised against the cytoplasmic epitope. We observed that Fas II-ir is accumulated
      at the cytoplasmic surfaces of pre- and postsynaptic elements of the synapse at
      equal distances from the membranes, thus supporting the model that it has a
      similar orientation in these opposing synaptic structures. Fas II-ir delineates
      active zones and is compartmentalized from CSP, Dap160, and Bruchpilot
      immunolabeling. We conclude that Fas II immunolabeling in Drosophila can be
      reliably used to evaluate changes in the size of the active zone region at rest
      in genetic and functional experiments.

PMID- 19850081
TI  - Oligonucleotide-based microarray for detection of plant viruses employing
      sequence-independent amplification of targets.
AB  - The potential of DNA microarrays for detection of plant viruses is hampered by
      underutilization of sequence-independent amplification methods for target nucleic
      acid enrichment. A microarray system is described for an unbiased detection of
      plant viruses using both short (30 nt) and long (50 and 70 nt) oligonucleotide
      probes. The assay involves amplification of target nucleic acid using random
      primers followed by in vitro transcription whose cRNA product is labeled
      chemically, fragmented and used as target for hybridization. Initial optimization
      tests with Turnip vein clearing virus and Cauliflower mosaic virus showed
      increased hybridization efficiency with shorter cDNA targets (100 bp) and longer
      probes (50 and 70 nt). The system was validated in pure and mixed samples by
      detection of three Tymovirus species: Asclepias asymptomatic virus, Kennedya
      yellow mosaic virus and Turnip yellow mosaic virus. The method could detect
      sequence variants with 70-75% or higher sequence identity, indicating the
      possible utility of the approach for virus discovery. Array performance
      comparison of long probes demonstrated the competence of 50-mers to provide a
      satisfactory balance between detection sensitivity and specificity. The work
      described is a significant step towards a method to assess, in one assay, the
      presence of a large diversity of relatives of known viruses of plants.

PMID- 19850082
TI  - Recollection of episodic memory within the medial temporal lobe: behavioural
      dissociations from other types of memory.
AB  - In recent years there has been significant debate about whether there is a single
      medial temporal lobe memory system or dissociable systems for episodic and other
      types of declarative memory. In addition there has been a similar debate over the
      dissociability of recollection and familiarity based processes in recognition
      memory. Here we present evidence from recent work using episodic memory tasks in
      animals that allows us to explore these issues in more depth. We review studies
      that demonstrate triple dissociations within the medial temporal lobe, with only
      the hippocampal system being necessary for episodic memory. Similarly we review
      behavioural evidence for a dissociation in a task of episodic memory in rats
      where animals with lesions of the fornix are only impaired at recollection of the
      episodic memory, not recognition within the same trial. This work, then, supports
      recent models of dissociable neural systems within the medial temporal lobe but
      also raises questions for future investigation about the interactions of these
      medial temporal lobe memory systems with other structures.

PMID- 19850083
TI  - Covert imitation of transitive actions activates effector-independent motor
      representations affecting "motor" knowledge of target-object properties.
AB  - The present study aimed at determining whether, and in what conditions, covert
      imitation of different manual grasps of the same object influences estimation of
      those object properties whose variations afford those different grasp
      interactions. Participants matched the size of spheres after observation of the
      same spheres being grasped using both a power and a precision grasp: these
      actions are used preferentially to grasp large and small objects, respectively.
      The type of matching varied across four experiments. In experiment 1,
      participants matched the object size by opening their thumb and index finger; in
      experiment 2, they abducted their index and middle fingers as in a finger opening
      of a cutting pantomime, and in experiment 3, they opened their mouth. In
      experiment 4, the sphere size was reproduced on a PC monitor by moving the mouse
      forward/backward. Grasp observation affected matching in experiments 1 and 3.
      Kinematics analysis showed overestimation after observation of a power grasp as
      compared to a precision grasp. The data are interpreted as a consequence of
      covert imitation of the observed hand kinematics, which varied congruently with
      the object sizes potentially activating that type-of-grasp. This affected
      estimation of object size. Covert imitation was favored by the types of matching
      requiring motor patterns related to grasp movements independently of the effector
      used. This finding supports the existence of motor commands to the hand as well
      as to the mouth, activated when the same potential goal guides the movements of
      both these effectors.

PMID- 19850084
TI  - Evaluating the behavioural consequences of early maternal separation in adult
      C57BL/6 mice; the importance of time.
AB  - Research in rats has shown that early maternal separation can have a significant
      effect on stress-associated neuro- and endocrine mechanisms in adulthood.
      However, despite a growing body of evidence on the neurobiology of early MS,
      showing significant overlap in data from rat, non-human primate and human
      studies, there is still some uncertainty about the validity of this model in
      mice. Here we present evidence in support of long lasting effects of early MS on
      adult mouse behaviour, which were only apparent when time was included as an
      analytical component. In the elevated plus maze (EPM), conventional statistical
      strategies, which typically evaluate behaviour as a summed test-session total,
      were not sufficient to reveal more complex time-dependent behavioural profiles.
      Specifically, the spatially more complex nature of the EPM test underscored
      treatment-related differences in the time-dependent adjustments of open arm
      exploration and risk-assessment behaviours. In contrast, the open field elicited
      an immediate and consistent divergence in risk-assessment behaviours, between MS
      animals and controls. Finally, plasma corticosterone further underscored MS
      associated alterations in adult mouse stress profiles, with significantly higher
      concentrations in the MS group, post-restraint stress. The extension of
      conventional analysis strategies, to include time as a significant dimension of
      behaviour on the EPM, identified behavioural nuances, which could reflect
      adaptive aspects of stress-driven behaviours in MS mice.

PMID- 19850085
TI  - Short-term total sleep deprivation in the rat increases antioxidant responses in
      multiple brain regions without impairing spontaneous alternation behavior.
AB  - Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral
      and cellular changes. We previously reported that long term (5-11 days) TSD in
      the rat, by the disk-over-water method, decreases the activity of the antioxidant
      enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain
      insight into the mechanisms causing cognitive impairment, here we explore the
      early associations between metabolic activity, antioxidant responses and working
      memory (one form of cognitive impairment). Specifically we investigated the
      impact of short-term (6h) TSD, by gentle handling, on the levels of the
      endogenous antioxidant, total glutathione (GSHt), and the activities of the
      antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short-term TSD had
      no significant impact on SOD activity, but increased GSHt levels in the rat
      cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus
      and cerebellum. We also observed increased activity of hexokinase, (HK), the rate
      limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We
      further showed that 6h of TSD leads to increased exploratory behavior to a new
      environment, without impairing spontaneous alternation behavior (SAB) in the Y
      maze. We conclude that acute (6h) sleep loss may trigger compensatory mechanisms
      (like increased antioxidant responses) that prevent initial deterioration in
      working memory.

PMID- 19850086
TI  - Neonatal motor functions in Cacna1a-mutant rolling Nagoya mice.
AB  - Rolling Nagoya mice show ataxia and carry a mutation in the Cacna1a gene, which
      encodes the pore-forming alpha1 subunit of the Cav2.1 channels. Because an
      impaired motor function has not been examined during neonatal stages in detail,
      we employed a battery of tests including assessments of body weight gain,
      righting reflex, negative geotaxis, hind-limb suspension, and tail suspension
      using neonatal wild-type, heterozygous, and homozygous rolling mice. We found
      deterioration of body weight gain after postnatal day 8 (P8) in the homozygous
      mice, as well as a longer latency time to complete the righting reflex and the
      negative geotaxis tests after P8. Additionally, the homozygous rolling mice
      exhibited lower pulling and holding attempts after P8 in the hind-limb suspension
      test. The mice heterozygous and homozygous for the rolling mutation exhibited
      muscle fatigue after P10 and P8, respectively, following movement execution tests
      administered immediately after the first trial, suggesting that gene dosage plays
      an important role in determining when muscle weakness occurs. The homozygous
      rolling mice showed hind-limb clasping or touching after P14 during the hind-limb
      and tail suspension tests. Our results indicate that the gait abnormality of
      neonatal rolling Nagoya would be due to the combination of muscle weakness and
      neuronal dysfunction and that the rolling mice could be a useful model for
      delineating neonatal motor deficiencies.

PMID- 19850087
TI  - Inflammatory protein sPLA(2)-IIA abrogates TNFalpha-induced apoptosis in human
      astroglioma cells: Crucial role of ERK.
AB  - Brain injury induces the expression of well-known cytokines, such as tumor
      necrosis factor-alpha (TNFalpha), and other, which functions are less understood,
      as secreted phospholipase A(2) group IIA (sPLA(2)-IIA). Since in pathological
      processes, cytokines function coordinately in networks, to further explore the
      actions of sPLA(2)-IIA in tumorigenesis, we investigated the effect of sPLA(2)
      IIA in the presence of TNFalpha in human 1321N1 astrocytoma cells. In these
      cells, TNFalpha activates the apoptotic programme that is accompanied of
      cytoskeleton changes; however, simultaneous treatment with sPLA(2)-IIA prevents
      TNFalpha-mediated apoptosis and reverses the modification of the markers
      associated to this response. In fact, the mitogenic activity elicited by the
      phospholipase alone is preserved. This inhibitory effect is not found in other
      TNFalpha-mediated responses, even a functional cooperation is observed on COX-2
      protein induction. The cross-talk between TNFalpha and sPLA(2)-IIA is associated
      with ERK activity since its pharmacological inhibition attenuates both
      synergistic and inhibitory responses. We have also observed that upon sPLA(2)-IIA
      stimulation, endogenous ERK has the capacity to bind and phosphorylate sequences
      present within the cytoplasmic domain of TNFR1/CD120a. These findings thus
      indicate that sPLA(2)-IIA and TNFalpha transduction pathways interact to modulate
      inflammatory responses and provide additional insights about the capacity of
      sPLA(2)-IIA to promote apoptosis resistance in astrocytoma cells.

PMID- 19850088
TI  - Identification and characterization of thermophilic bacteria isolated from hot
      springs in Turkey.
AB  - The present study was conducted to identify and characterize the thermophilic
      bacteria isolated from various hot springs in Turkey by using phenotypic and
      genotypic methods including fatty acid methyl ester and rep-PCR profilings, and
      16S rRNA sequencing. The data of fatty acid analysis showed the presence of 17
      different fatty acids in 15 bacterial strains examined in this study. Six fatty
      acids, 15:0 iso, 15:0 anteiso, 16:0, 16:0 iso, 17:0 iso, and 17:0 anteiso, were
      present in all strains. The bacterial strains were classified into three
      phenotypic groups based on fatty acid profiles which were confirmed by genotypic
      methods such as 16S rRNA sequence analysis and rep-PCR genomic fingerprint
      profiles. After evaluating several primer sets targeting the repetitive DNA
      elements of REP, ERIC, BOX and (GTG)(5), the (GTG)(5) and BOXA1R primers were
      found to be the most reliable technique for identification and taxonomic
      characterization of thermophilic bacteria in the genera of Geobacillus,
      Anoxybacillus and Bacillus spp. Therefore, rep-PCR fingerprinting using the
      (GTG)(5) and BOXA1R primers can be considered as a promising genotypic tool for
      the identification and characterization of thermophilic bacteria from species to
      strain level.

PMID- 19850089
TI  - A self-deleting Cre-lox-ermAM cassette, Cheshire, for marker-less gene deletion
      in Streptococcus pneumoniae.
AB  - Although targeted mutagenesis of Streptococcus pneumoniae is readily accomplished
      with the aid of natural genetic transformation and chimeric donor DNA constructs
      assembled in vitro, the drug resistance markers often employed for selection of
      recombinant products can themselves be undesirable by-products of the genetic
      manipulation. A new cassette carrying the erythromycin-resistance marker ermAM
      that can be used as a temporary marker for selection of desired recombinants is
      described. The cassette may subsequently be removed at will by virtue of an
      embedded fucose-regulated Cre recombinase gene and terminal lox66 and lox71 Cre
      recognition sites, with retention of 34bp from the cassette as an inert residual
      double-mutant lox72 site.

PMID- 19850090
TI  - Effect of reaction conditions and 3AB on the mutation rate of poliovirus RNA
      dependent RNA polymerase in a alpha-complementation assay.
AB  - The fidelity of poliovirus RNA-dependent RNA polymerase (3Dpol) was determined
      using a modified alpha-complementation assay. Several polymerases have been
      analyzed by this approach allowing comparisons to be drawn. Various conditions
      including high and low MgCl(2), replacing MgCl(2) with MnCl(2), skewed nucleotide
      pools, and the presence of poliovirus protein 3AB were analyzed. The assay
      included RNA synthesis by 3Dpol on an RNA template that coded for a region of the
      alpha peptide of beta-galactosidase (lacZ-alpha). The product of this reaction
      was used as a template for a second round of 3Dpol synthesis and the resulting
      RNA was reverse transcribed to DNA by reverse transcriptase. The DNA was
      amplified by PCR and inserted into a vector used to transform Escherichia coli.
      The bacteria were screened for beta-galactosidase activity by blue-white
      phenotype analysis with white or faint blue colonies scored as errors made during
      synthesis on lacZ-alpha. Although 3AB strongly stimulated 3Dpol synthesis as
      expected, no change in fidelity was detected. Changes in MgCl(2) also showed
      little effect. Mutation rates of approximately 9 x 10(-5) (approximately 1 error
      per 11,000 incorporations) were estimated for these conditions. In contrast,
      MnCl(2) or skewed nucleotide pools were highly mutagenic resulting in lowered
      fidelity.

PMID- 19850091
TI  - Effects of methodology and analysis strategy on robustness of pestivirus
      phylogeny.
AB  - Phylogenetic analysis of pestiviruses is a useful tool for classifying novel
      pestiviruses and for revealing their phylogenetic relationships. In this study,
      robustness of pestivirus phylogenies has been compared by analyses of the 5'UTR,
      and complete N(pro) and E2 gene regions separately and combined, performed by
      four methods: neighbour-joining (NJ), maximum parsimony (MP), maximum likelihood
      (ML), and Bayesian inference (BI). The strategy of analysing the combined
      sequence dataset by BI, ML, and MP methods resulted in a single, well-supported
      tree topology, indicating a reliable and robust pestivirus phylogeny. By
      contrast, the single-gene analysis strategy resulted in 12 trees of different
      topologies, revealing different relationships among pestiviruses. These results
      indicate that the strategies and methodologies are two vital aspects affecting
      the robustness of the pestivirus phylogeny. The strategy and methodologies
      outlined in this paper may have a broader application in inferring phylogeny of
      other RNA viruses.

PMID- 19850092
TI  - Impact of emulsion-based drug delivery systems on intestinal permeability and
      drug release kinetics.
AB  - Lipid based drug delivery systems, and in particular self-emulsifying drug
      delivery systems (SEDDS), show great potential for enhancing oral bioavailability
      but have not been broadly applied, largely due to lack of general formulation
      guidance. To help understand how formulation design influences physicochemical
      emulsion properties and associated function in the gastrointestinal environment,
      a range of twenty-seven representative self-emulsifying formulations were
      investigated. Two key functions of emulsion-based drug delivery systems,
      permeability enhancement and drug release, were studied and statistically related
      to three formulation properties - oil structure, surfactant hydrophilic
      liphophilic balance (HLB) values, and surfactant-to-oil ratio. Three surfactants
      with HLB values ranging from 10 to 15 and three structurally different oils (long
      chain triglyceride, medium chain triglyceride, and propylene glycol
      dicaprylate/dicaprate) were combined at three different weight ratios (1:1, 5:1,
      9:1). Unstable formulations of low HLB surfactant (HLB=10) had a toxic effect on
      cells at high (1:1) surfactant concentrations, indicating the importance of
      formulation stability for minimizing toxicity. Results also indicate that high
      HLB surfactant (Tween 80) loosens tight junction at high (1:1) surfactant
      concentrations. Release coefficients for each emulsion system were calculated.
      Incorporation of a long chain triglyceride (Soybean oil) as the oil phase
      increased the drug release rate constant. These results help establish an initial
      foundation for relating emulsion function to formulation design and enabling
      bioavailability optimization across a broad, representative range of SEDDS
      formulations.

PMID- 19850093
TI  - Naturally derived materials-based cell and drug delivery systems in skin
      regeneration.
AB  - The objective of regenerative medicine is to provide cells with a local
      environment of artificial extracellular matrix where they can proliferate and
      differentiate efficiently and therefore, induce the repair of defective tissues
      according to the natural healing potential of patients. For this purpose,
      naturally derived materials are being widely used because of their similarities
      to the extracellular matrix, typically good biocharacteristics and inherent
      cellular interaction. Also, natural polymers can be engineered to release growth
      factors and related agents in response to physiologic signals to imitate the
      natural healing process and to promote fast tissue regeneration and reduce
      scarring in wounds. Although synthetic materials have been used extensively in
      tissue engineering fields, this review illustrates the contribution of natural
      materials and natural materials-based protein delivery systems to regenerative
      medicine research, with emphasis on the application of multifunctional vehicles
      for cell and growth factor delivery in skin regeneration research.

PMID- 19850094
TI  - CpG motifs in pDNA-sequences increase anti-PEG IgM production induced by PEG
      coated pDNA-lipoplexes.
AB  - Gene therapy is largely dependent on the development of efficient delivery
      vehicles. To prolong their circulating time, PEGylation of the surface of a
      delivery vehicle is frequently applied. However, we have reported previously that
      anti-PEG IgM produced by intravenous injection of PEG-coated liposome is
      responsible for enhanced clearance of second dose PEG-coated liposomes, which is
      known as the "accelerated blood clearance (ABC) phenomenon." A similar phenomenon
      has been observed with PEG-coated pDNA-lipoplexes (PDCLs) upon their repeated
      injection. But the effect of the sequence of pDNA in PDCLs on inducing the ABC
      phenomenon has not been thoroughly investigated. Here, we focus on CpG motifs in
      pDNA, which are known to have a potent immune-stimulatory activity. PDCLs with
      non-CpG pDNA (PNDCL) diminished the anti-PEG IgM response, resulting in
      significant accumulation of a second dose in tumor tissue, comparable to that of
      a single injection, but not in enhanced accumulation in liver. In addition, PDCL
      induced proliferation of IgM(+) splenic cells including B cells. These results
      suggest that the CpG motif is a major cause of the induction of the ABC
      phenomenon when PDCLs are repeatedly injected. Immunogenicity is a relevant point
      of concern for non-viral delivery systems. Our results indicate that the use of
      non-CpG pDNA may allow meaningful repeated dosing of pDNA formulations without
      the induction of a strong immune reaction and thus may have important
      implications for therapeutic use of liposomal formulations of nucleic acids.

PMID- 19850095
TI  - Nanotechnology and the transdermal route: A state of the art review and critical
      appraisal.
AB  - The skin is refractive to most molecules, especially hydrophilic ones, despite
      the existence of trans-barrier pathways. It is essential to maintain this
      protective barrier even after breaching skin surface for purposes of transdermal
      drug delivery to cope with cutaneous microbiota. Mechanical abraders or local
      energy dischargers (porators) or else hard, sharp objects (perforators, micro
      needles) can punch a limited number (approximately 10(2)cm(-2)) of relatively
      wide (> or =10(3)nm) openings in the skin barrier, which then lets transiently
      (approximately 1 day) small drug quantities (< or =10 mg) and even large
      molecules (and pathogens?) pass. Microscopic (> or =10(3)nm) ballistic droplets
      or particles also insert small drug amounts (approximately 1mg) into the upper
      skin through the > or =10(6)cm(2) pores they create. The latter "skin breaching"
      method is approved for use in humans, whereas the hard nano-sized (5 nm-10
      microm) skin perforators are still in development for transdermal drug delivery.
      Alternatively, controlled and reliable drug delivery across skin barrier can be
      achieved with sufficiently deformable and stable nano-sized carriers. Such "soft"
      skin penetrators are typically composite colloids. As such they must obtain, or
      retain, their ability to act as drug carriers on, in, and ideally below skin
      barrier(s). If properly designed and applied, such self-regulating, ultra
      adaptable, and stable hetero-aggregates can open spontaneously and carry drugs
      through < or =10(9)cm(-2) cutaneous pores in the primary skin barrier and
      minimise cutaneous drug clearance; this permits deep/targeted deposition and
      prolonged action of the carrier-transported drugs. Therapeutic products based on
      ultra-adaptable, self-regulating, nano-sized (approximately 10(2)nm) carriers are
      under development. The first one is already approved in Switzerland.

PMID- 19850096
TI  - Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide
      administration.
AB  - Accumulated evidence has indicated that neuroinflammation is one of the important
      etiologic factors of Parkinson's disease (PD). Earlier studies have employed the
      inflammogen lipopolysaccharide (LPS) to induce inflammation of dopaminergic
      neurons. Methamphetamine (MA) dopaminergic toxicity similar to 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) toxicity is frequently cited as a model of PD.
      In the present study, we examined whether striatal LPS exposure potentiates MA
      induced dopaminergic toxicity. Combined treatment with LPS and MA significantly
      potentiates behavioral impairment and dopaminergic deficit. However, this
      combination did not significantly alter the other monoaminergic systems (e.g.,
      serotonin, norepinephrine, and histamine). Consistently, microglial activation,
      labeled by F4/80 or Iba-1 in the nigrostriatal region was more pronounced with
      the combined treatment of LPS and MA compared to either treatment alone, but this
      combination did not significantly alter the microglial activation in other brain
      regions (e.g., hippocampus, dorsal raphe nuclei, and locus ceruleus).
      Furthermore, neuroinflammation, oxidative stress, and pro-apoptotic changes in
      the striatum were more accentuated with combined treatment of LPS and MA compared
      to either treatment alone. In addition, it is important that cytoplasmic
      accumulation of alpha-synuclein was observed in the substantia nigra of mice
      treated with LPS plus MA, and that L-Dopa treatment significantly attenuated
      behavioral changes and dopaminergic deficits induced by LPS plus MA. These
      results suggest that combined treatment of LPS with MA is a potential animal
      model for PD.

PMID- 19850097
TI  - Exposure of newborns to aflatoxin M1 and B1 from mothers' breast milk in Ankara,
      Turkey.
AB  - Aflatoxins (AFs) are important risks for human health due to their widespread
      presence in foods and environment. However, contamination risk of breast milk
      with different pollutants including AFs is high in today's life conditions. Since
      breast milk is a major nutrient for infants, feeding of infants with safe milk is
      essential. Therefore, the objective of this study was to determine the levels of
      AF M(1) and B(1) in breast milk samples collected from 75 mothers in Ankara,
      Turkey. AF M(1) and B(1) levels were investigated by high performance liquid
      chromatography (HPLC) with a fluorescence detector following an extraction
      procedure. The limit of detection was found to be 5 ng/l. Both AFs were detected
      in diverse degrees in all breast milk samples: The level of AF M(1) were in the
      ranges of 60.90-299.99 ng/l, and AF B(1) were in the ranges of 94.50-4123.80
      ng/l. These results pointed out the exposure of mothers and neonates to AF M(1)
      and B(1), and the necessity of further research on mycotoxin contamination both
      in foods and biological fluids as well as protection strategies.

PMID- 19850098
TI  - Assessment of dermal toxicity of nanosilica using cultured keratinocytes, a human
      skin equivalent model and an in vivo model.
AB  - Assessments of skin irritation potentials are important aspects of the
      development of nanotechnology. Nanosilica is currently being widely used for
      commercial purposes, but little literature is available on its skin toxicity and
      irritation potential. This study was designed to determine whether nanosilica has
      the potential to cause acute cutaneous toxicity, using cultured HaCaT
      keratinocytes (CHK), a human skin equivalent model (HSEM), and invivo model.
      Nanosilica was characterized by scanning electron microscopy. We evaluated the
      cytotoxic effects of nanosilica on CHKs and the HSEM. In addition, we also
      investigated whether two commercially available nanosilicas with different sizes
      (7 and 10-20 nm) have different effects. To confirm invitro results, we evaluated
      the irritation potentials of nanosilicas on rabbit skin. Nanosilicas reduced the
      cell viabilities of CHKs in a dose-dependent manner. However, the HSEM revealed
      no irritation at 500 microg/ml of nanosilica. Furthermore, this result concurred
      with Draize skin irritation test findings. The present study data indicate that
      nanosilica does not cause acute cutaneous irritation. Furthermore, this study
      shows that the HSEM used provides more useful screening data than the
      conventional cell culture model on the relative toxicities of NPs.

PMID- 19850099
TI  - Aromatic hydrocarbons upregulate glyceraldehyde-3-phosphate dehydrogenase and
      induce changes in actin cytoskeleton. Role of the aryl hydrocarbon receptor
      (AhR).
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme
      involved in several cellular functions including glycolysis, membrane transport,
      microtubule assembly, DNA replication and repair, nuclear RNA export, apoptosis,
      and the detection of nitric oxide stress. Therefore, modifications in the
      regulatory ability and function of GAPDH may alter cellular homeostasis. We
      report here that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta
      naphthoflavone, which are well-known ligands for the aryl hydrocarbon receptor
      (AhR), increase GAPDH mRNA levels in vivo and in vitro, respectively. These
      compounds fail to induce GAPDH transcription in an AhR-null mouse model,
      suggesting that the increase in GAPDH level is dependent upon AhR activation. To
      analyse the consequences of AhR ligands on GAPDH function, mice were treated with
      TCDD and the level of liver activity of GAPDH was determined. The results showed
      that TCDD treatment increased GAPDH activity. On the other hand, treatment of
      Hepa-1 cells with beta-naphthoflavone leads to an increase in microfilament
      density when compared to untreated cultures. Collectively, these results suggest
      that AhR ligands, such as polycyclic hydrocarbons, can modify GAPDH expression
      and, therefore, have the potential to alter the multiple functions of this
      enzyme.

PMID- 19850100
TI  - Targeting specific cell signaling transduction pathways by dietary and medicinal
      phytochemicals in cancer chemoprevention.
AB  - Natural phytochemicals derived from dietary sources or medicinal plants have
      gained significant recognition in the potential management of several human
      clinical conditions. Much research has also been geared towards the evaluation of
      plant extracts as effective prophylactic agents since they can act on specific
      and/or multiple molecular and cellular targets. Plants have been an abundant
      source of highly effective phytochemicals which offer great potential in the
      fight against cancer by inhibiting the process of carcinogenesis through the
      upregulation of cytoprotective genes that encode for carcinogen detoxifying
      enzymes and antioxidant enzymes. The mechanistic insight into chemoprevention
      further includes induction of cell cycle arrest and apoptosis or inhibition of
      signal transduction pathways mainly the mitogen-activated protein kinases (MAPK),
      protein kinases C (PKC), phosphoinositide 3-kinase (PI3K), glycogen synthase
      kinase (GSK) which lead to abnormal cyclooxygenase-2 (COX-2), activator protein-1
      (AP-1), nuclear factor-kappaB (NF-kappaB) and c-myc expression. Effectiveness of
      chemopreventive agents reflects their ability to counteract certain upstream
      signals that leads to genotoxic damage, redox imbalances and other forms of
      cellular stress. Targeting malfunctioning molecules along the disrupted signal
      transduction pathway in cancer represent a rational strategy in chemoprevention.
      NF-kappaB and AP-1 provide mechanistic links between inflammation and cancer, and
      moreover regulate tumor angiogenesis and invasiveness, indicating that signaling
      pathways that mediate their activation provide attractive targets for new
      chemotherapeutic approaches. Thus cell signaling cascades and their interacting
      factors have become important targets of chemoprevention and phenolic
      phytochemicals and plant extracts seem to be promising in this endeavor.

PMID- 19850101
TI  - Chemical signaling in the nervous system in health and disease: Nils-Ake
      Hillarp's legacy.

PMID- 19850102
TI  - Receptor-receptor interactions: A novel concept in brain integration.
AB  - A brief historical presentation of the hypothesis on receptor-receptor
      interactions as an important integrative mechanism taking place at plasma
      membrane level is given. Some concepts derived from this integrative mechanism
      especially the possible assemblage of receptors in receptor mosaics (high-order
      receptor oligomers) and their relevance for the molecular networks associated
      with the plasma membrane are discussed. In particular, the Rodbell's
      disaggregation theory for G-proteins is revisited in the frame of receptor mosaic
      model. The paper also presents some new indirect evidence on A2A;D2 receptor
      interactions obtained by means of Atomic Force Microscopy on immunogold
      preparations of A2A and D2 receptors in CHO cells. These findings support
      previous data obtained by means of computer-assisted confocal laser microscopy.
      The allosteric control of G-protein coupled receptors is examined in the light of
      the new views on allosterism and recent data on a homocysteine analogue capable
      of modulating D2 receptors are shown. Finally, the hypothesis is introduced on
      the existence of check-points along the amino acid pathways connecting allosteric
      and orthosteric binding sites of a receptor and their potential importance for
      drug development.

PMID- 19850103
TI  - Comparison of melanin-concentrating hormone and hypocretin/orexin peptide
      expression patterns in a current parceling scheme of the lateral hypothalamic
      zone.
AB  - The distribution of hypothalamic neurons expressing the peptides melanin
      concentrating hormone (MCH; 'MCH neurons') or hypocretin/orexin (H/O; 'H/O
      neurons') was assessed with immunocytochemistry in male rats at high spatial
      resolution. Data were plotted on a rat brain atlas that includes a recently
      revised parcellation scheme for the lateral hypothalamic zone. Quantitative
      analysis revealed approximately three times more MCH neurons than H/O neurons in
      the hypothalamus, and approximately twice as many within the parcellations of the
      lateral hypothalamic area (LHA). The LHA contained 60% of MCH neurons and 81% of
      H/O neurons, and the same five LHA regions contained the vast majority of MCH
      (87%) or H/O (93%) neurons present within the LHA: namely the LHA dorsal region
      (LHAd: 31% of H/O; 38% of MCH), suprafornical region (LHAs: 28% of H/O; 11% of
      MCH), ventral region medial zone (LHAvm: 15% of H/O; 16% of MCH),
      juxtadorsomedial region (LHAjd: 14% of H/O and MCH) and magnocellular nucleus
      (LHAm: 5% of H/O; 7% of MCH). The zona incerta (ZI) contained 18% of MCH neurons.
      A high co-abundance of MCH and H/O neurons outside of the LHA was present in the
      posterior hypothalamic nucleus (PH: 11% of H/O; 9% of MCH). Morphological
      analysis revealed MCH and H/O neurons as typically tri-polar with irregularly
      shaped somata. These data provide a quantitative analysis of neurons expressing
      either MCH or H/O peptides within the rat hypothalamus, and they clarify
      differences in the distribution pattern for different subsets of these neuron
      types, especially within the LHA.

PMID- 19850105
TI  - Changes in plasma brain-derived neurotrophic factor levels in smokers after
      smoking cessation.
AB  - Several studies have reported that brain-derived neurotrophic factor (BDNF) might
      be associated with nicotine dependence. However, there are few studies on BDNF
      levels in humans with nicotine dependence. In the present study, we compared the
      differences in plasma BDNF levels in patients with nicotine dependence and in
      healthy nonsmokers, and we investigated serial changes in plasma BDNF levels in
      patients with nicotine dependence following smoking cessation. Forty-five
      voluntary smokers and 66 nonsmokers were recruited in this study. Of the 45
      smokers, 12 were taking varenicline, 21 were using a nicotine patch, and 12 were
      unaided in their cessation effort by their own choice. Plasma BDNF levels were
      measured at baseline using an enzyme-linked immunosorbent assay (both smokers and
      nonsmokers) and at weeks 4 and 12 after smoking cessation (abstinent smokers
      only). A total of 19 smokers were able to remain abstinent during the entire
      study period. Baseline plasma BDNF levels were significantly lower in smokers
      compared to nonsmokers (F=4.410, p=0.002). The plasma BDNF levels in the
      abstinent smokers significantly increased from baseline after 4 weeks of smoking
      cessation (z=-2.86, p=0.004) but had a tendency of decrease in the period between
      weeks 4 and 12. We could not find differences in the plasma BDNF levels among the
      three smoker subgroups at week 12 following cessation. Changes in plasma BDNF
      levels might be related to the process of abstinence and the pathophysiology of
      nicotine dependence.

PMID- 19850104
TI  - Deletion of both the C3a and C5a receptors fails to protect against experimental
      autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is an autoimmune disease in which inflammation, leukocyte
      infiltration, and ultimately, demyelination occur as a result of innate and
      adaptive immune-mediated mechanisms. The pathophysiological role of the
      complement system, a major component of innate immunity, in the development and
      progression of experimental autoimmune encephalomyelitis (EAE), the animal model
      for MS has been extensively examined. Previous studies from our lab have shown
      that the complement receptor for the anaphylatoxin C3a, but not for C5a plays an
      important role in EAE. Based on the important contributions of the complement
      anaphylatoxin receptors to other inflammatory conditions in the CNS, we reasoned
      that deletion of both receptors may reveal underlying interactions between them
      that are important to EAE pathology. We performed EAE in C3aR/C5aR double
      knockout mice (C3aR/C5aR(-/-)) and observed delayed onset of disease but no
      attenuation of disease severity compared to wild type mice. Interestingly there
      was trend toward greater infiltration of CD4(+), but not CD8(+) T cells, in
      C3aR/C5aR(-/-) mice with EAE, suggesting altered trafficking of these cells.
      Antigen-specific T cells isolated from C3aR/C5aR(-/-) mice during acute EAE
      produced elevated levels of TNF-alpha, but markedly reduced levels of IFN-gamma
      and IL-12 compared to wild type mice. It remains unclear how the changes in these
      disease parameters contribute to the loss of the protective effect seen in C3aR(
      /-) mice, however our data indicate a level of cross-modulation between the C3aR
      and C5aR during EAE.

PMID- 19850106
TI  - Inhibition of glutamate transporters couples to Kv4.2 dephosphorylation through
      activation of extrasynaptic NMDA receptors.
AB  - Activation of glutamate receptors is known to modulate K(+) channel surface
      trafficking, phosphorylation, and function, and increasing evidence has
      implicated K(+) channels in plastic changes in glutamatergic synapses. Kv4.2
      channels control the amplitude of back-propagating action potentials and shape
      postsynaptic responses in hippocampus, and synaptic glutamate receptor activation
      leads to increased phosphorylation of Kv4.2 channels that is associated with
      enhanced synaptic plasticity. Thus, we investigated the possibility that
      activation of extrasynaptic NMDA-type glutamate receptors couples to Kv4.2
      channel dephosphorylation. In hippocampal neurons, we found that selective
      activation of extrasynaptic NMDA receptors dephosphorylates Kv4.2 channels, and
      driving synaptic activity increases phosphorylation of Kv4.2. We also observed
      that Ca(2+) entry through NMDA receptors is necessary for dephosphorylation of
      Kv4.2 channels. Consistent with a synaptic and extrasynaptic localization at
      hippocampal synapses, a fraction of Kv4.2 channel clusters was found to localize
      outside of pre- and postsynaptic markers. Excitatory amino acid transporters
      (EAATs) regulate ambient extracellular glutamate levels that active extrasynaptic
      NMDA receptors, and inhibition of glutamate uptake by blocking EAATs with the non
      selective transporter inhibitor dl-threo-beta-benzyloxyaspartic acid (TBOA) or
      the EAAT1/3 selective inhibitor l-serine O-sulfate (SOS) dephosphorylates Kv4.2
      channels. These findings in conjunction with previous reports support the
      interesting possibility that synaptic and extrasynaptic NMDA receptors bi
      directionally regulate phosphorylation levels of Kv4.2 channels in hippocampus.
      Moreover, we observed that EAAT activity controls extrasynaptic NMDA receptor
      modulation of Kv4.2 channel dephosphorylation.

PMID- 19850108
TI  - Aquaglyceroporin 9 in brain pathologies.
AB  - Aquaglyceroporins belong to the aquaporin family and are permeable to water and
      also to small solutes such as glycerol and urea. In this review, we will compare
      the expression of aquaporin 9 (AQP9), an aquaglyceroporin, with that of AQP4, a
      pure water channel, in pathological conditions. In astrocytes, AQP4 is mainly
      involved in water and ionic homeostasis. Its expression is highly modified in
      several brain disorders and it plays a key role in cerebral edema formation. AQP9
      is expressed in astrocytes and in catecholaminergic neurons. The level of
      expression of brain AQP9 is under the control of blood insulin concentrations,
      and its expression is increased in diabetes, suggesting that AQP9 could be
      involved in brain energy metabolism. The induction of AQP9 in astrocytes is
      observed over time after stroke onset, suggesting participation in the clearance
      of excess lactate in the extracellular space. In some models, AQP9 is also
      induced in non-catecholaminergic neurons after global ischemia and in the
      periphery of gliomas, however functional roles are still unclear. The review of
      literature underlies that each AQP has several distinctive roles which depend on
      the AQP and cell types.

PMID- 19850109
TI  - Regulation of water permeability through aquaporin-4.
AB  - Aquaporin-4 (AQP4) is a predominant water channel protein in mammalian brains
      that is distributed with the highest density in the perivascular and subpial
      astrocyte end-feet. AQP4 is a critical component of an integrated water and
      potassium homeostasis. Expression and regulation of AQP4 have been studied to
      understand the roles of AQP4 in physiology and several pathological conditions.
      Indeed, AQP4 has been implicated in several neurological conditions, such as
      brain edema and seizure. AQP4 is dynamically regulated at different levels:
      channel gating, subcellular distribution, phosphorylation, protein-protein
      interactions and orthogonal array formation. In this review, we focus on the
      short-term regulation of AQP4. Phosphorylation of AQP4 is important; AQP4 is
      inhibited when Ser180 is phosphorylated and activated when Ser111 is
      phosphorylated. AQP4 is also regulated by several metal ions. These metal ions
      inhibit AQP4 by interacting with the Cys178 residue located in the cytoplasmic
      loop D, suggesting that AQP4 is regulated by intracellular signaling pathways in
      response to extracellular stimuli. Recently, it was demonstrated that AQP4 may be
      inhibited by arylsulfonamides, antiepileptic drugs and other related chemical
      compounds. Structural analysis of AQP4 may guide a drug design for AQP4.

PMID- 19850107
TI  - Molecular disruptions of the panglial syncytium block potassium siphoning and
      axonal saltatory conduction: pertinence to neuromyelitis optica and other
      demyelinating diseases of the central nervous system.
AB  - The panglial syncytium maintains ionic conditions required for normal neuronal
      electrical activity in the central nervous system (CNS). Vital among these
      homeostatic functions is "potassium siphoning," a process originally proposed to
      explain astrocytic sequestration and long-distance disposal of K(+) released from
      unmyelinated axons during each action potential. Fundamentally different, more
      efficient processes are required in myelinated axons, where axonal K(+) efflux
      occurs exclusively beneath and enclosed within the myelin sheath, precluding
      direct sequestration of K(+) by nearby astrocytes. Molecular mechanisms for entry
      of excess K(+) and obligatorily-associated osmotic water from axons into
      innermost myelin are not well characterized, whereas at the output end, axonally
      derived K(+) and associated osmotic water are known to be expelled by Kir4.1 and
      aquaporin-4 channels concentrated in astrocyte endfeet that surround capillaries
      and that form the glia limitans. Between myelin (input end) and astrocyte endfeet
      (output end) is a vast network of astrocyte "intermediaries" that are strongly
      inter-linked, including with myelin, by abundant gap junctions that disperse
      excess K(+) and water throughout the panglial syncytium, thereby greatly reducing
      K(+)-induced osmotic swelling of myelin. Here, I review original reports that
      established the concept of potassium siphoning in unmyelinated CNS axons,
      summarize recent revolutions in our understanding of K(+) efflux during axonal
      saltatory conduction, then describe additional components required by myelinated
      axons for a newly-described process of voltage-augmented "dynamic" potassium
      siphoning. If any of several molecular components of the panglial syncytium are
      compromised, K(+) siphoning is blocked, myelin is destroyed, and axonal saltatory
      conduction ceases. Thus, a common thread linking several CNS demyelinating
      diseases is the disruption of potassium siphoning/water transport within the
      panglial syncytium. Continued progress in molecular identification and
      subcellular mapping of glial ion and water channels will lead to a better
      understanding of demyelinating diseases of the CNS and to development of improved
      treatment regimens.

PMID- 19850110
TI  - Caprospinol reduces amyloid deposits and improves cognitive function in a rat
      model of Alzheimer's disease.
AB  - Alzheimer's disease (AD), the most prominent form of dementia in elderly, is a
      yet incurable degenerative neurological illness characterized by memory loss.
      Here, we used an AD rat model to investigate the in vivo efficacy of caprospinol,
      a disease-modifying steroid developed on the concept that reduced synthesis of
      22R-hydroxycholesterol in the AD brain increases beta-amyloid neurotoxicity.
      Caprospinol treatment of diseased rats attenuated memory impairment, as assessed
      using Morris watermaze tests. This recovery of cognitive function was accompanied
      by a reduction in hippocampal amyloid deposits, astrogliosis, neurodegeneration
      and Tau protein phopshorylation. In parallel studies, caprospinol bioavailability
      in normal rat forebrain was found to be dependent on the dose and duration of the
      treatment, demonstrating the ability of the compound to cross the blood-brain
      barrier. These results position caprospinol as a promising drug candidate for AD
      treatment.

PMID- 19850111
TI  - Cadherin-19 expression is restricted to myelin-forming cells in the chicken
      embryo.
AB  - We cloned chicken cadherin-19 that demonstrates high similarity to human and rat
      cadherin-19. Chicken cadherin-19 is a type II classic cadherin that is located on
      the long arm of chicken chromosome 2 and is composed of 13 exons and 12 introns.
      The expression profile of cadherin-19 was analyzed by semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization during
      chicken embryonic development. Its expression starts at E2.5, then gradually
      increases to reach a peak at E20. In contrast to previous results obtained in
      rat, chicken cadherin-19 is expressed both in Schwann cells and oligodendrocytes,
      also at late stages of development. We found no other cell type positive for
      cadherin-19 in the chicken embryo throughout development, suggesting that
      cadherin-19 is selectively expressed by myelin-forming cells and might play a
      role in myelin formation. The sequence of cadherin-19 shares high similarity with
      that of cadherin-7 and cadherin-20, and the three genes form a cluster on
      chromosome 2. Their expression patterns, however, are rather distinct although
      partial overlap is observed. For example, cadherin-19 and cadherin-7 are co
      expressed by Schwann cells but not by oligodendrocytes. Moreover, a subset of
      interneurons express cadherin-7 but not cadherin-19 or cadherin-20. Despite their
      close genetic relation, the three cadherins have acquired functions in rather
      different cell types during nervous system development.

PMID- 19850112
TI  - Evaluation of a new eastern blotting technique for the analysis of ginsenoside Re
      in American ginseng berry pulp extracts.
AB  - A new eastern blotting technique has been established for ginsenoside Re (G-Re)
      contained in American ginseng berry pulp extracts. G-Re in American ginseng berry
      pulp was extracted using 100% methanol, 100% ethanol, 50% aqueous methanol, and
      50% aqueous ethanol. The combined crude extracts were applied onto a
      polyethersulfone membrane and developed using the methanol-water-acetic acid
      solvent system (45:55:1 v/v). Separated components were immunostained using anti
      G-Re monoclonal antibody. G-Re was first specifically detected and then
      quantitatively analyzed using NIH Imaging software. We also confirmed that the
      most suitable solvent was 50% aqueous methanol for extracting G-Re from American
      ginseng berry pulp.

PMID- 19850113
TI  - Fine-scale analysis of synchronous breathing in wild Indo-Pacific bottlenose
      dolphins (Tursiops aduncus).
AB  - We quantitatively analysed synchronous breathing for dyads in Indo-Pacific
      bottlenose dolphins at Mikura Island, Tokyo, Japan. For most cases, we observed
      dyads swimming in the same direction (97%), in close proximity (i.e., less than
      1.5m) and with their body axes parallel as they breathed synchronously. Moreover,
      the pairs engaged in identical behaviour before and after the synchronous
      breathing episodes. These results suggest that the dolphins synchronize their
      movements, and that synchronous breathing is a component of "pair-swimming", an
      affiliative social behaviour. Same sex pairs of the same age class frequently
      engaged in synchronous breathing for adults and subadults, as well as mother-calf
      and escort-calf pairs. The distance between individuals during synchronous
      breathing for mother-calf pairs was less than for other pairs. The distance
      observed between individuals for female pairs was less than for male pairs. The
      time differences between each exhale for each of the two dolphins involved in
      synchronous breathing episodes for female pairs were smaller than for male pairs,
      and time differences for adult pairs were smaller than subadult pairs. These
      results suggest that age and sex class influenced the characteristics of this
      behaviour.

PMID- 19850114
TI  - Oestrous females investigate the unfamiliar male more than the familiar male in
      both commensal and non-commensal populations of house mice.
AB  - We studied female preferences for familiar and unfamiliar males. The subjects
      were laboratory-born house mice: (1) non-commensal Mus musculus domesticus from
      the eastern part of Syria along the Euphrates River; and (2) commensal M. m.
      musculus from the Czech Republic. Pair-choice preference tests have revealed that
      oestrous females of both populations sniffed towards unfamiliar males more than
      familiar males. In the case of females exhibiting postpartum oestrus, this
      preference was less pronounced and statistically not significant. Thus, our mice
      clearly exhibited the behavioural pattern known from commensal populations of
      polygynous and/or promiscuous M. m. domesticus. We found no inverse tendency to
      seek proximity to the familiar male that has been previously reported from
      closely related and presumably monogamous aboriginal mouse Mus spicilegus. We
      conclude that neither commensal M. m. musculus, nor non-commensal M. m.
      domesticus, are likely to share a monogamous mating system with mound-building
      mice.

PMID- 19850115
TI  - Effects on bone tissue in ewes (Ovies aries) and their foetuses exposed to PCB
      118 and PCB 153.
AB  - The aim of the present study was to investigate whether low levels of mono-ortho
      PCB 118 and di-ortho PCB 153, affect bone composition and strength in ewes (Dala
      breed) and their foetuses following exposure starting at conception and ending a
      week before expected delivery. In male foetuses, trabecular bone mineral content
      at the metaphysis was almost 30% lower in the PCB 118 (49 microg/kg body wt/day)
      group compared to the control group (corn oil) (ANCOVA, P<0.05). In female
      foetuses of the PCB 153 (98 microg/kg body wt/day) group trabecular cross
      sectional area at the metaphysis was 19% smaller than in the controls (ANCOVA,
      P<0.05). At the diaphysis a smaller marrow cavity area (up to 24% reduction) was
      observed in female and male foetuses exposed to PCB 153 compared with controls
      (ANCOVA, P<0.05). There were also significant differences at the mid diaphyseal
      measure point between the PCB 153 and the control group females (ANCOVA, P<0.05).
      Cortical and total bone mineral density, cortical thickness were significantly
      higher, endosteal circumference shorter and marrow cavity significantly smaller
      in the PCB 153 group (ANCOVA, P<0.05). In conclusion there were gender dependent
      effects on bone tissue and cortical bone was more affected than trabecular bone.

PMID- 19850116
TI  - Recording of electrically evoked auditory brainstem responses after electrical
      stimulation with biphasic, triphasic and precision triphasic pulses.
AB  - Biphasic electrical pulses are the standard stimulation pulses in current
      cochlear implants. In auditory brainstem recordings biphasic pulses generate a
      significant artifact that disrupts brainstem responses, which are magnitudes
      smaller. Triphasic pulses may minimize artifacts by restoring the neural membrane
      to its resting potential faster than biphasic pulses and make auditory brainstem
      responses detection easier. We compared biphasic pulses with triphasic and
      precision triphasic pulses to evoke brainstem responses in human subjects. For
      this purpose, electrically evoked brainstem response audiometry was performed in
      10 (11 ears) cochlear implant patients. Artifacts and brainstem responses evoked
      by bi- and triphasic stimulation were analyzed. Artifact amplitude and decay time
      were related to pulse pattern shape, but application of averaging and alternation
      reduced the deterioration of electrically evoked brainstem responses independent
      of pulse pattern shape. Contrary to our expectations, biphasic pulses showed a
      higher detectability in comparison to triphasic pulse stimulation at the same
      stimulation amplitude.

PMID- 19850117
TI  - Light signaling genes and their manipulation towards modulation of phytonutrient
      content in tomato fruits.
AB  - Due to its economic importance, ease of genetic manipulation, cultivation and
      processing, the tomato plant has been a target for increasing and diversifying
      content of fruit phytonutrients by transgenic and non-transgenic approaches. The
      tomato high pigment (hp) mutations exemplify the latter alternative and due to
      their positive effect on fruit lycopene content, they were introgressed into
      elite tomato germplasm for cost effective extraction of this important
      carotenoid. Interestingly, hp mutant fruits are also characterized by higher
      fruit levels of other functional metabolites, phenotypes caused by mutations in
      central genes regulating light signal-transduction. This gene identification
      suggests that modulation of light signaling machinery in plants may be highly
      effective towards manipulation of fruit phytonutrients but has never been
      thoroughly reviewed. This review therefore summarizes the progress which has been
      made on this valuable approach, emphasizing the consequences of transgenic
      modulation of light signaling components on the functional properties of the
      tomato fruit.

PMID- 19850118
TI  - Ripening of fleshy fruit: molecular insight and the role of ethylene.
AB  - Development and ripening in fruit is a unique phase in the life cycle of higher
      plants which encompasses several stages progressively such as fruit development,
      its maturation, ripening and finally senescence. During ripening phase, several
      physiological and biochemical changes take place through differential expression
      of various genes that are developmentally regulated. Expression and/or
      suppression of these genes contribute to various changes in the fruit that make
      it visually attractive and edible. However, in fleshy fruit massive losses accrue
      during post harvest handling of the fruit which may run into billions of dollars
      worldwide. This encouraged scientists to look for various ways to save these
      losses. Genetic engineering appears to be the most promising and cost effective
      means to prevent these losses. Most fleshy fruit ripen in the presence of
      ethylene and once ripening has been initiated proceeds uncontrollably. Ethylene
      evokes several responses during ripening through a signaling cascade and
      thousands of genes participate which not only sets in ripening but also
      responsible for its spoilage. Slowing down post ripening process in fleshy fruit
      has been the major focus of ripening-related research. In this review article,
      various developments that have taken place in the last decade with respect to
      identifying and altering the function of ripening-related genes have been
      described. Role of ethylene and ethylene-responsive genes in ripening of fleshy
      fruit is also included. Taking clues from the studies in tomato as a model fruit,
      few case studies are reviewed.

PMID- 19850119
TI  - Assay conditions can influence the outcome of cytotoxicity tests of
      nanomaterials: better assay characterization is needed to compare studies.
AB  - BACKGROUND: Reliable in vitro studies that generate consistent toxicity data on
      nanomaterials on a high-throughput scale will be of invaluable significance in
      the next few years. AIM: In this study, we checked the influence of several steps
      of the experimental design on the outcome: we investigated the role of cell
      density, viability assay and particle dispersion method, including the influence
      of serum and effect of a surfactant (Tween 80). METHODS: The dose-response curve
      was assessed for ground multiwalled carbon nanotubes (CNT) and the silica
      benchmark Min-U-Sil, on lung epithelial cells (A549 cells) and macrophages
      (stimulated THP-1 cells). RESULTS: The cell density used in the cytotoxicity
      study has an impact on the outcome: for the same concentration of Min-U-Sil, the
      viability of A549 cells varied from 10% to 55% with increasing cell density.
      Whereas foetal calf serum attenuated the cytotoxicity of Min-U-Sil, this effect
      was not seen for CNT. The results show how cell culture conditions can modify the
      outcome of a toxicological experiment, as shown in this study for Tween 80 to
      disperse the test agent. CONCLUSIONS: These experiments illustrates that results
      reported in literature can only be compared when, in addition to the use of a
      benchmark particle, a detailed method description is available. Therefore, more
      emphasis is needed on a standardized design for cytotoxicity studies.

PMID- 19850120
TI  - NG108-15 cell-based and protein phosphatase inhibition assays as alternative
      semiquantitative tools for the screening of lipophilic toxins in mussels. Okadaic
      acid detection.
AB  - We report the application of a cell-based assay (CBA) using NG108-15 a hybridoma
      cell strain and a protein phosphatase inhibition-based assay (PPIA) as
      alternative toxicological or functional semiquantitative tools, respectively, for
      the screening of lipophilic toxins in mussels (Mytilusgalloprovincialis).
      Acetonic extracts were directly tested by CBA and PPIA but severe matrix effects
      were observed. As a solution, a simple 17-fraction protocol with solid-phase
      extraction (SPE) cartridges was optimised and applied as a previous step to the
      CBA or the PPIA. LC-MS/MS analyses were performed in parallel to determine the
      lipophilic toxins content in mussel extracts. Evaluation of the SPE protocol by
      LC-MS/MS showed okadaic acid (OA) recovery above 90% and negligible effects of
      mussel matrix on the SPE performance. The whole methods provided limits of
      detection of 47 and 45mug OA equivalents/kg for CBA and PPIA, respectively. The
      combined strategy permitted the identification of OA toxicity in two fractions,
      and allowed us to clearly distinguish between negative and positive samples, the
      latter being either OA-spiked or naturally-contaminated samples at levels equal
      or above the regulatory limit. The combination of fractioning with CBA or PPIA
      allows the quantification of the toxic and functional effects of samples above
      these concentrations.

PMID- 19850121
TI  - Chlorpyrifos induced reproductive toxicity in male mice.
AB  - The reproductive toxicity of the insecticide chloropyrifos was studied in male
      mice. Adult male mice were treated by gavage with chloropyrifos at doses of 0, 5,
      15, and 25mg/kg-d for 4 weeks before mating with untreated females. Signs of
      cholinergic effects were observed in the 15 and 25mg/kg-d treated groups. Brain
      and skeletal muscle acetylcholinesterase activity was inhibited in the same
      groups. Chloropyrifos treatment was associated with a decreased number of live
      fetuses, and an increased number of dead fetuses at 25mg/kg-d. The number of
      early resorption was decreased in both 15 and 25mg/kg-d treated groups. The
      percent morphologically normal spermatozoa were affected in 15 and 25mg/kg-d dose
      groups; however, sperm motility and count were decreased in the same treated
      groups compared to the control. Histologic examination of brain revealed
      histological abnormalities in the middle and high groups. Dose related histologic
      changes, including degeneration of muscle fibers, were observed in the muscles of
      male mice treated with all the doses of chloropyrifos. The current study
      demonstrated adverse effects of male chloropyrifos exposure on pregnancy outcome
      with effects on sperm parameters at 15 and 25mg/kg-d.

PMID- 19850122
TI  - An overview of male reproductive studies of boron with an emphasis on studies of
      highly exposed Chinese workers.
AB  - Boron treatment of rats, mice, and dogs has been associated with testicular
      toxicity, characterized by inhibited spermiation at lower dose levels and a
      reduction in epididymal sperm count at higher dose levels. The no-adverse-effect
      level for reproductive effects in male rats is 17.5mg B/kg bw/day. Earlier
      studies in human workers and populations have not identified adverse effects of
      boron exposure on fertility, but outcome measures in these studies were
      relatively insensitive, based mainly on family size and did not include an
      evaluation of semen end points. A recent study of nearly 1000 men working in
      boron (B) mining or processing in Liaoning province in northeast China has been
      published in several Chinese and a few English language papers. This study
      included individual assessment of boron exposure, interview data on reproductive
      experience and semen analysis. Employed men living in the same community and in a
      remote community were used as controls. Boron workers (n=75) had a mean daily
      boron intake of 31.3mg B/day, and a subset of 16 of these men, employed at a
      plant where there was heavy boron contamination of the water supply, had an
      estimated mean daily boron intake of 125 mg B/day. Estimates of mean daily boron
      intake in local community and remote background controls were 4.25mg B/day and
      1.40 mg/day, respectively. Reproductive outcomes in the wives of 945 boron
      workers were not significantly different from outcomes in the wives of 249
      background control men after adjustment for potential confounders. There were no
      statistically significant differences in semen characteristics between exposure
      groups, including in the highly exposed subset, except that sperm Y:X ratio was
      reduced in boron workers. Within exposure groups the Y:X ratio did not correlate
      with the boron concentration in blood, semen and urine. In conclusion, while
      boron has been shown to adversely affect male reproduction in laboratory animals,
      there is no clear evidence of male reproductive effects attributable to boron in
      studies of highly exposed workers.

PMID- 19850123
TI  - Reproductive development and function of female rats exposed to di-eta-butyl
      phthalate (DBP) in utero and during lactation.
AB  - Phthalates are environmental contaminants used in the production of plastics,
      cosmetics and medical devices. Studies on the effects of phthalates on female
      reproductive health are particularly sparse and mostly restricted to high-dose
      exposure in rats. In the present study, pregnant rats were treated with 100mg/kg
      d of di-eta-butyl-phthalate (DBP) or only the vehicle (control group), from GD 12
      to GD 20 for evaluation of reproductive outcomes and fetal gonads analysis (F0),
      and from GD 12 to PND 21 to evaluate reproductive development and function on F1
      female offspring. Results showed that all parameters were comparable between
      groups, although there was a significant increase in the fetal weight after DBP
      exposure. However, the body weight at birth was normal. Based on these data we
      can conclude that, in these experimental conditions, DBP did not disturb the
      reproductive development or function of female rats.

PMID- 19850124
TI  - VPA-related axial skeletal defects and apoptosis: a proposed event cascade.
AB  - VPA axial malformations are related to embryonic somitic histone
      hyperacetylation. In cancer, histone hyperacetylation activates apoptosis. To
      verify if apoptosis is involved in somitic abnormalities, VPA-exposed embryos
      were evaluated for DNA fragmentation and for pro- (p53, acetylated p53, caspase
      3) and anti-apoptotic (Sirt 1) protein expression. Pregnant mice were i.p. dosed
      on day 8 with VPA 400mg/kg or TSA (16 mg/kg). Embryos, collected 3, 5, 9 or 24h
      after treatment, were examined and processed for apoptosis or protein analysis.
      An event cascade has been observed at the level of somites and proposed as
      related to VPA-induced axial skeletal defects: increased p53 (3h), DNA
      fragmentation (9h), abnormalities (24h). TSA, used as alternative HDAC inhibitor,
      induced apoptosis and somitic abnormalities, strengthening our hypothesized link
      between HDAC inhibition and axial defects.

PMID- 19850125
TI  - Common CYP7A1 promoter polymorphism associated with risk of neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is a severe idiopathic inflammatory disease of the
      central nervous system primarily affecting the optic nerves and spinal cord. In
      this study, we generated genome-wide SNP data from NMO patients and normal
      controls (53 cases and 240 controls), and followed up on the association signals
      with samples from a larger number of inflammatory demyelinating diseases,
      including NMO (n=93), multiple sclerosis (MS, n=71), idiopathic recurrent
      transverse myelitis (IRTM, n=57), and normal controls (n=240). Statistical
      analyses revealed that a common promoter SNP in CYP7A1 has a protective/gene dose
      dependent effect on the risk of NMO (P=0.0004). A stronger association between
      the variables and subsequently, a higher protective effect (lower OR) on the risk
      of NMO were observed among patients carrying the "G/G" genotype of rs3808607 than
      those with the "T/G" genotype (OR=0.38/P=0.01 vs. OR=0.12/P=0.0004,
      respectively). The associations which were only observed in patients with NMO
      suggest that there are differences in the genetic etiology of the inflammatory
      demyelinating diseases (NMO, classical MS, and IRTM).

PMID- 19850126
TI  - Aberrant modulation of a delayed rectifier potassium channel by glutamate in
      Alzheimer's disease.
AB  - In Alzheimer's disease (AD), potassium channel abnormalities have been reported
      in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we
      demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T
      lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients
      were similar to healthy individuals, glutamate (1-1000 microM) failed to yield
      the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation
      (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate),
      resulting in a 4-fold increase of resting channel activity. Specific agonist and
      antagonist data indicate that this abnormality is due to dysfunction of cognate
      group II mGluRs. Given that glutamate is present in plasma and that both mGluRs
      and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may
      account for the presence of immune-associated alterations in AD. Furthermore, if
      this aberration reflects a corresponding one in neural tissue, it could provide a
      potential target in AD pathogenesis.

PMID- 19850127
TI  - VPS41, a protein involved in lysosomal trafficking, is protective in
      Caenorhabditis elegans and mammalian cellular models of Parkinson's disease.
AB  - VPS41 is a protein identified as a potential therapeutic target for Parkinson's
      disease (PD) as a result of a high-throughput RNAi screen in Caenorhabditis
      elegans. VPS41 has a plausible mechanistic link to the pathogenesis of PD, as in
      yeast it is known to participate in trafficking of proteins to the lysosomal
      system and several recent lines of evidence have pointed to the importance of
      lysosomal system dysfunction in the neurotoxicity of alpha-synuclein (alpha-syn).
      We found that expression of the human form of VPS41 (hVPS41) prevents dopamine
      (DA) neuron loss induced by alpha-syn overexpression and 6-hydroxydopamine (6
      OHDA) neurotoxicity in C. elegans. In SH-SY5Y neuroblastoma cell lines stably
      transfected with hVPS41, we determined that presence of this protein conferred
      protection against the neurotoxins 6-OHDA and rotenone. Overexpression of hVPS41
      did not alter the mitochondrial membrane depolarization induced by these
      neurotoxins. hVPS41 did, however, block downstream events in the apoptotic
      cascade including activation of caspase-9 and caspase-3, and PARP cleavage. We
      also observed that hVPS41 reduced the accumulation of insoluble high-molecular
      weight forms of alpha-syn in SH-SY5Y cells after treatment with rotenone. These
      data show that hVPS41 is protective against both alpha-syn and neurotoxic
      mediated injury in invertebrate and cellular models of PD. These protective
      functions may be related to enhanced clearance of misfolded or aggregated
      protein, including alpha-syn. Our studies indicate that hVPS41 may be a useful
      target for developing therapeutic strategies for human PD.

PMID- 19850128
TI  - Astrocyte secreted proteins selectively increase hippocampal GABAergic axon
      length, branching, and synaptogenesis.
AB  - Astrocytes modulate the formation and function of glutamatergic synapses in the
      CNS, but whether astrocytes modulate GABAergic synaptogenesis is unknown. We
      demonstrate that media conditioned by astrocytes, but not other cells, enhanced
      GABAergic but not glutamatergic axon length and branching, and increased the
      number and density of presynaptically active GABAergic synapses in dissociated
      hippocampal cultures. Candidate mechanisms and factors, such as activity,
      neurotrophins, and cholesterol were excluded as mediating these effects. While
      thrombospondins secreted by astrocytes are necessary and sufficient to increase
      hippocampal glutamatergic synaptogenesis, they do not mediate astrocyte effects
      on GABAergic synaptogenesis. We show that the factors in astrocyte conditioned
      media that selectively affect GABAergic neurons are proteins. Taken together, our
      results show that astrocytes increase glutamatergic and GABAergic synaptogenesis
      via different mechanisms and release one or more proteins with the novel
      functions of increasing GABAergic axon length, branching and synaptogenesis.

PMID- 19850131
TI  - Specific metabolites in the medial prefrontal cortex are associated with the
      neurocognitive deficits in schizophrenia: a preliminary study.
AB  - We measured brain metabolites in the medial prefrontal cortex of 19 schizophrenic
      patients and 18 healthy controls by 3 T proton magnetic resonance spectroscopy
      ((1)H MRS), and examined the relationship between prefrontal cortex-related
      neurocognitive functions and brain metabolites in the medial prefrontal cortex.
      The patients with schizophrenia exhibited deficits on the verbal fluency,
      Wisconsin card sorting test (WCST), trail making test, Stroop test and digit span
      distraction test (DSDT), but not on the Iowa gambling test. The patients showed
      statistical significant changes in the ratio of glutamine/glutamate, the ratio of
      N-acetyl-l-aspartate (NAA)/glycerophosphorylcholine plus phosphorylcholine
      (GPC+PC) and the levels of taurine in the medial prefrontal cortex compared with
      normal controls. Furthermore, we found significant correlations of the ratio of
      glutamine/glutamate with WCST and DSDT scores, the ratio of NAA/(GPC+PC) with
      verbal fluency and WCST scores, and the levels of taurine with scores on the
      Stroop test and Trail making test A among the participants. The ratios of
      NAA/(GPC+PC) and (GPC+PC)/(Cr+PCr) had significant relationships with the
      duration of untreated psychosis of the schizophrenic patients. The
      glutamine/glutamate ratio and levels of taurine were significantly related to the
      duration of illness of the patients. These data suggest that specific metabolites
      of the medial prefrontal cortex are associated with the neurocognitive deficits
      in schizophrenia.

PMID- 19850129
TI  - An activity-induced microRNA controls dendritic spine formation by regulating
      Rac1-PAK signaling.
AB  - Activity-regulated gene expression is believed to play a key role in the
      development and refinement of neuronal circuitry. Nevertheless, the
      transcriptional networks that regulate synaptic plasticity remain largely
      uncharacterized. We show here that the CREB- and activity-regulated microRNA,
      miR132, is induced during periods of active synaptogenesis. Moreover, miR132 is
      necessary and sufficient for hippocampal spine formation. Expression of the
      miR132 target, p250GAP, is inversely correlated with miR132 levels and
      spinogenesis. Furthermore, knockdown of p250GAP increases spine formation while
      introduction of a p250GAP mutant unresponsive to miR132 attenuates this activity.
      Inhibition of miR132 decreases both mEPSC frequency and the number of GluR1
      positive spines, while knockdown of p250GAP has the opposite effect.
      Additionally, we show that the miR132/p250GAP circuit regulates Rac1 activity and
      spine formation by modulating synapse-specific Kalirin7-Rac1 signaling. These
      data suggest that neuronal activity regulates spine formation, in part, by
      increasing miR132 transcription, which in turn activates a Rac1-Pak actin
      remodeling pathway.

PMID- 19850130
TI  - The leucine rich amelogenin protein (LRAP) adsorbs as monomers or dimers onto
      surfaces.
AB  - Amelogenin is believed to be involved in controlling the formation of the highly
      anisotropic and ordered hydroxyapatite crystallites that form enamel. The
      adsorption behavior of amelogenin proteins onto substrates is very important
      because protein-surface interactions are critical to its function. We have
      previously used LRAP, a splice variant of amelogenin, as a model protein for the
      full-length amelogenin in solid-state NMR and neutron reflectivity studies at
      interfaces. In this work, we examined the adsorption behavior of LRAP in greater
      detail using model self-assembled monolayers containing COOH, CH(3), and NH(2)
      end groups as substrates. Dynamic light scattering (DLS) experiments indicated
      that LRAP in phosphate buffered saline and solutions containing low
      concentrations of calcium and phosphate consisted of aggregates of nanospheres.
      Null ellipsometry and atomic force microscopy (AFM) were used to study protein
      adsorption amounts and quaternary structures on the surfaces. Relatively high
      amounts of adsorption occurred onto the CH(3) and NH(2) surfaces from both buffer
      solutions. Adsorption was also promoted onto COOH surfaces only when calcium was
      present in the solutions suggesting an interaction that involves calcium bridging
      with the negatively charged C-terminus. The ellipsometry and AFM studies revealed
      that LRAP adsorbed onto the surfaces as small subnanosphere-sized structures such
      as monomers or dimers. We propose that the monomers/dimers were present in
      solution even though they were not detected by DLS or that they adsorbed onto the
      surfaces by disassembling or "shedding" from the nanospheres that are present in
      solution. This work reveals the importance of small subnanosphere-sized
      structures of LRAP at interfaces.

PMID- 19850132
TI  - MRI visualization of endogenous neural progenitor cell migration along the RMS in
      the adult mouse brain: validation of various MPIO labeling strategies.
AB  - The adult rodent brain contains neural progenitor cells (NPCs), generated in the
      subventricular zone (SVZ), which migrate along the rostral migratory stream (RMS)
      towards the olfactory bulb (OB) where they differentiate into neurons. The aim of
      this study was to visualize endogenous NPC migration along the RMS with magnetic
      resonance imaging (MRI) in adult healthy mice. We evaluated various in situ (in
      vivo) labeling approaches using micron-sized iron oxide particles (MPIOs) on
      their efficiency to label endogenous NPCs. In situ labeling and visualization of
      migrating NPCs were analyzed by a longitudinal MRI study and validated with
      histology. Here, we visualized endogenous NPC migration in the mouse brain by in
      vivo MRI and demonstrated accumulation of MPIO-labeled NPCs in the OB over time
      with ex vivo MRI. Furthermore, we investigated the influence of in situ injection
      of MPIOs on adult neurogenesis. Quantitative analysis of bromodeoxyuridine
      labeled cells revealed altered proliferation in the SVZ and NPC migration after
      in situ MPIO injection. From the labeling strategies presented in this report,
      intraventricular injection of a small number of MPIOs combined with the
      transfection agent poly-l-lysine hydrobromide was the best method as labeling of
      the NPCs was successful and proliferation in the SVZ was only marginally
      affected. While MRI visualization of endogenous NPC migration can provide insight
      into aberrant NPC migration in disease models, this work emphasizes the
      importance to carefully explore the impact on adult neurogenesis when new in situ
      labeling strategies are developed.

PMID- 19850133
TI  - Longitudinal characterization of brain atrophy of a Huntington's disease mouse
      model by automated morphological analyses of magnetic resonance images.
AB  - Mouse models of human diseases play crucial roles in understanding disease
      mechanisms and developing therapeutic measures. Huntington's disease (HD) is
      characterized by striatal atrophy that begins long before the onset of motor
      symptoms. In symptomatic HD, striatal volumes decline predictably with disease
      course. Thus, imaging based volumetric measures have been proposed as outcomes
      for presymptomatic as well as symptomatic clinical trials of HD. Magnetic
      resonance imaging of the mouse brain structures is becoming widely available and
      has been proposed as one of the biomarkers of disease progression and drug
      efficacy testing. However, three-dimensional and quantitative morphological
      analyses of the brains are not straightforward. In this paper, we describe a tool
      for automated segmentation and voxel-based morphological analyses of the mouse
      brains. This tool was applied to a well-established mouse model of Huntington's
      disease, the R6/2 transgenic mouse strain. Comparison between the automated and
      manual segmentation results showed excellent agreement in most brain regions. The
      automated method was able to sensitively detect atrophy as early as 4 weeks of
      age and accurately follow disease progression. Comparison between ex vivo and in
      vivo MRI suggests that the ex vivo end-point measurement of brain morphology is
      also a valid approach except for the morphology of the ventricles. This is the
      first report of longitudinal characterization of brain atrophy in a mouse model
      of Huntington's disease by using automatic morphological analysis.

PMID- 19850135
TI  - Reconstruction of correlated brain activity with adaptive spatial filters in MEG.
AB  - Adaptive spatial filters (beamformers) have gained popularity as an effective
      method for the localization of brain activity from magnetoencephalography (MEG)
      data. Among the attractive features of some beamforming methods are high spatial
      resolution and no localization bias even in the presence of random noise. A
      drawback common to all beamforming methods, however, is significant degradation
      in performance in the presence of sources with high temporal correlations. Using
      numerical simulations and examples of auditory and visual evoked field responses,
      we demonstrate that, at typical signal-to-noise levels, the complete attenuation
      of fully correlated brain activity is less likely to occur, although significant
      localization and amplitude biases may occur. We compared various methods for
      correcting these biases and found the coherent source suppression model (CSSM)
      (Dalal et al., 2006) to be the most effective, with small biases for widely
      separated sources (e.g., bilateral auditory areas), however, amplitude biases
      increased systematically as distance between the sources was decreased. We
      assessed the performance and systematic biases that may result from the use of
      this model, and confirmed our findings with real examples of correlated brain
      activity in bilateral occipital and inferior temporal areas evoked by visually
      presented faces in a group of 21 adults. We demonstrated the ability to localize
      source activity in both regions, including correlated sources that are in close
      proximity ( approximately 3 cm) in bilateral primary visual cortex when using a
      priori information regarding source location. We conclude that CSSM, when
      carefully applied, can significantly improve localization accuracy, although
      amplitude biases may remain.

PMID- 19850134
TI  - Negative covariation between task-related responses in alpha/beta-band activity
      and BOLD in human sensorimotor cortex: an EEG and fMRI study of motor imagery and
      movements.
AB  - Similar to the occipital alpha rhythm, electroencephalographic (EEG) signals in
      the alpha- and beta-frequency bands can be suppressed by movement or motor
      imagery and have thus been thought to represent the "idling state" of the
      sensorimotor cortex. A negative correlation between spontaneous alpha EEG and
      blood-oxygen-level-dependent (BOLD) signals has been reported in combined EEG and
      fMRI (functional Magnetic Resonance Imaging) experiments when subjects stayed at
      the resting state or alternated between the resting state and a task. However,
      the precise nature of the task-induced alpha modulation remains elusive. It was
      not clear whether alpha/beta rhythm suppressions may co-vary with BOLD when
      conducting tasks involving varying activations of the cortex. Here, we quantified
      the task-evoked responses of BOLD and alpha/beta-band power of EEG directly in
      the cortical source domain, by using source imaging technology, and examined
      their covariation across task conditions in a mixed block and event-related
      design. In this study, 13 subjects performed tasks of right-hand, right-foot or
      left-hand movement and motor imagery when EEG and fMRI data were separately
      collected. Task-induced increase of BOLD signal and decrease of EEG amplitudes in
      alpha and beta bands were shown to be co-localized at the somatotopic
      sensorimotor cortex. At the corresponding regions, the reciprocal changes of the
      two signals co-varied in the magnitudes across imagination and movement
      conditions. The spatial correspondence and negative covariation between the two
      measurements were further shown to exist at somatotopic brain regions associated
      with different body parts. These results suggest an inverse functional coupling
      relationship between task-induced changes of BOLD and low-frequency EEG signals.

PMID- 19850136
TI  - Multiple indicators of age-related differences in cerebral white matter and the
      modifying effects of hypertension.
AB  - We investigated differences associated with age and hypertension, a common risk
      factor for vascular disease, in three aspects of white matter integrity--gross
      regional volumes of the white matter, volume of the white matter hyperintensities
      (WMH) and diffusion properties. We acquired MRI scans on 93 adult volunteers (age
      50-77 years; 36 with diagnosis of hypertension or elevated blood pressure), and
      obtained all measures in seven brain regions: frontal, temporal, parietal and
      occipital white matter, and the genu, body and splenium of the corpus callosum.
      The results demonstrated robust age-related differences in diffusion-based
      indices of cerebral white matter integrity and age-related increase in the WMH
      volume, but no age differences in the gross regional volumes of the white matter.
      Hypertension was associated with decline in fractional anisotropy, and
      exacerbated age differences in fractional anisotropy more than those in the
      volume of WMH. These findings indicate that of all examined measures, diffusion
      based indices of white matter integrity may be the most sensitive indicators of
      global and regional declines and vascular damage in the aging brain.

PMID- 19850137
TI  - Associations between the size of the amygdala in infancy and language abilities
      during the preschool years in normally developing children.
AB  - Recently, structural MRI studies in children have been used to examine relations
      between brain volume and behavioral measures. However, most of these studies have
      been done in children older than 2 years of age. Obtaining volumetric measures in
      infants is considerably more difficult, as structures are less well defined and
      largely unmyelinated, making segmentation challenging. Moreover, it is still
      unclear whether individual anatomic variation across development, in healthy,
      normally developing infants, is reflected in the configuration and function of
      the mature brain and, as importantly, whether variation in infant brain structure
      might be related to later cognitive and linguistic abilities. In this
      longitudinal study, using T1 structural MRI, we identified links between amygdala
      volume in normally developing, naturally sleeping, 6-month infants and their
      subsequent language abilities at 2, 3 and 4 years. The images were processed and
      manually segmented using Cardviews to extract volumetric measures. Intra-rater
      reliability for repeated segmentation was 87.73% of common voxel agreement.
      Standardized language assessments were administered at 6 and 12 months and at 2,
      3 and 4 years. Significant and consistent correlations were found between
      amygdala size and language abilities. Children with larger right amygdalae at 6
      months had lower scores on expressive and receptive language measures at 2, 3,
      and 4 years. Associations between amygdala size and language outcomes have been
      reported in children with autism. The findings presented here extend this
      association to normally developing children, supporting the idea that the
      amygdalae might play an important but as yet unspecified role in mediating
      language acquisition.

PMID- 19850139
TI  - White matter architecture rather than cortical surface area correlates with the
      EEG alpha rhythm.
AB  - There are few studies on the neuroanatomical determinants of EEG spectral
      properties that would explain its substantial inter-individual variability in
      spite of decades of biophysical modeling that predicts this type of relationship.
      An exception is the negative relation between head size and the spectral position
      of the alpha peak (P(alpha)) reported in Nunez et al. (1978)-proposed as evidence
      of the influence of global boundary conditions on slightly damped neocortical
      waves. Here, we attempt to reexamine this finding by computing the correlations
      of occipital P(alpha) with various measures of head size and cortical surface
      area, for 222 subjects from the EEG/MRI database of the Cuban Human Brain Mapping
      Project. No relation is found (p>0.05). On the other hand, biophysical models
      also predict that white matter architecture, determining time delays and
      connectivities, could have an important influence on P(alpha). This led us to
      explore relations between P(alpha) and DTI fractional anisotropy by means of a
      multivariate penalized regression. Clusters of voxels with highly significant
      relations were found. These were positive within the Posterior and Superior
      Corona Radiata for both hemispheres, supporting biophysical theories predicting
      that the period of cortico-thalamocortical cycles might be modulating the alpha
      frequency. Posterior commissural fibers of the Corpus Callosum present the
      strongest relationships, negative in the inferior part (Splenium), connecting the
      inferior occipital lobes and positive in the superior part (Isthmus and Tapetum),
      connecting the superior occipital cortices. We found that white matter
      architecture rather than neocortical area determines the dynamics of the alpha
      rhythm.

PMID- 19850138
TI  - Altered white matter microstructure in the corpus callosum in Huntington's
      disease: implications for cortical "disconnection".
AB  - The corpus callosum (CC) is the major conduit for information transfer between
      the cerebral hemispheres and plays an integral role in relaying sensory, motor
      and cognitive information between homologous cortical regions. The majority of
      fibers that make up the CC arise from large pyramidal neurons in layers III and
      V, which project contra-laterally. These neurons degenerate in Huntington's
      disease (HD) in a topographically and temporally selective way. Since any focus
      of cortical degeneration could be expected to secondarily de-afferent homologous
      regions of cortex, we hypothesized that regionally selective cortical
      degeneration would be reflected in regionally selective degeneration of the CC.
      We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified
      corpus callosum segmentation scheme to examine the CC in healthy controls,
      huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal
      callosal cross-sectional thickness and several DTI parameters, including
      fractional anisotropy (FA), which reflects the degree of white matter
      organization, radial diffusivity, a suggested index of myelin integrity, and
      axial diffusivity, a suggested index of axonal damage of the CC. We found a
      topologically selective pattern of alterations in these measures in pre-manifest
      subjects that were more extensive in early symptomatic HD subjects and that
      correlated with performance on distinct cognitive measures, suggesting an
      important role for disrupted inter-hemispheric transfer in the clinical symptoms
      of HD. Our findings provide evidence for early degeneration of commissural
      pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and
      functional compromise of associative cortical processing.

PMID- 19850140
TI  - Errors can be related to pre-stimulus differences in ERP topography and their
      concomitant sources.
AB  - Much of the variation in both neuronal and behavioral responses to stimuli can be
      explained by pre-stimulus fluctuations in brain activity. We hypothesized that
      also errors are the result of stochastic fluctuations in pre-stimulus activity
      and investigated the temporal dynamics of the scalp topography and their
      concomitant intracranial generators of stimulus- and response-locked high-density
      event-related potentials (ERPs) to errors and correct trials in a Stroop task. We
      found significant differences in ERP map topography and intracranial sources
      before the onset of the stimulus and after the initiation of the response but not
      as a function of stimulus-induced conflict. Before the stimulus, topographic
      differences were accompanied by differential activity in lateral frontal,
      parietal and temporal areas known to be involved in voluntary reorientation of
      attention and cognitive control. Differential post-response activity propagated
      both medially and laterally on a rostral-caudal axis of a network typically
      involved in performance monitoring. Analysis of the statistical properties of
      error occurrences revealed their stochasticity.

PMID- 19850142
TI  - Genetic variability within the Oudri's fan-footed gecko Ptyodactylus oudrii in
      North Africa assessed using mitochondrial and nuclear DNA sequences.
AB  - We analyse for the first time the genetic diversity within Ptyodactylus oudrii
      across the Maghreb. Two mitochondrial (12s rRNA and 16s rRNA) and two nuclear (C
      mos and ACM4) markers are used. The results confirm the specific status of P.
      oudrii and show high levels of intraspecific variability, indicative of species
      complex. Lineages found are geographically concordant, and show similar patterns
      to that found in other species from the region. The study highlights once more
      the importance of the region as a source of genetic diversity.

PMID- 19850141
TI  - Two extinct diploid progenitors were involved in allopolyploid formation in the
      Hordeum murinum (Poaceae: Triticeae) taxon complex.
AB  - Wall barley (Hordeum murinum) occurs with three subspecies, naturally distributed
      from southern Central Asia through the Mediterranean region to northwestern
      Europe, but now is an invasive weed in many parts of the world. Subspecies
      glaucum is diploid, while subspp. murinum and leporinum are tetraploids, the
      latter also occurring with a hexaploid cytotype. Earlier analyses were
      inconclusive regarding auto- or allopolyploid origins of subspp. murinum and
      leporinum. We analyzed the phylogeny of the taxon group using amplified fragment
      length polymorphisms (AFLP), sequences of cloned PCR products of the nuclear
      ribosomal DNA internal transcribed spacer region (ITS), a part of the nuclear
      single-copy gene topoisomerase 6 (Topo6) spanning two introns, and sequences of
      the chloroplast trnL-F region together with length variation at six chloroplast
      microsatellite loci, including multiple individuals of each subspecies and
      cytotype, covering the entire natural distribution area of the species.
      Phylogenetic analyses with all used markers differentiate diploid and polyploids.
      Sequences of both nuclear regions indicated that diploid subsp. glaucum was
      involved in tetraploid formation together with a now extinct species belonging to
      the same Hordeum genome group (Xu). Furthermore, AFLP and ITS analyses suggest
      that a third, though closely related extinct taxon contributed to hexaploid
      formation. No method was able to discern tetraploid subspp. murinum and
      leporinum, which we attribute to the young age of subsp. murinum. None of the
      used molecular markers revealed a strong geographic pattern of genetic variation
      that would allow comprehensive phylogeographic analysis, most probably due to the
      very effective seed dispersal of the taxa.

PMID- 19850143
TI  - Molecular phylogeography and population structure of a mid-elevation montane frog
      Leptobrachium ailaonicum in a fragmented habitat of southwest China.
AB  - Leptobrachium ailaonicum is a vulnerable anuran restricted to a patchy
      distribution associated with small mountain streams surrounded by forested slopes
      at mid-elevations (approximately 2000-2600m) in the subtropical Mount Wuliang and
      Mount Ailao ranges in southwest China (Yunnan Province) and northern Vietnam.
      Given high habitat specificity and lack of suitable habitat in lower elevations
      between these ranges, we hypothesized limited gene flow between populations
      throughout its range. We used two mitochondrial genes to construct a
      phylogeographic pattern within this species in order to test our hypothesis. We
      also examined whether this phylogeographic pattern is a response to past
      geological events and/or climatic oscillations. A total of 1989 base pairs were
      obtained from 81 individuals of nine populations yielding 51 unique haplotypes.
      Both Bayesian and maximum parsimony phylogenetic analyses revealed four deeply
      divergent and reciprocally monophyletic mtDNA lineages that approximately
      correspond to four geographical regions separated by deep river valleys. These
      results suggest a long history of allopatric separation by vicariance. The
      distinct geographic distributions of four major clades and the estimated
      divergence time suggest spatial and temporal separations that coincide with
      climatic and paleogeographic changes following the orogeny and uplift of Mount
      Ailao during the late Miocene to mid Pliocene in southwest China. At the southern
      distribution, the presence of two sympatric yet differentiated clades in two
      areas are interpreted as a result of secondary contact between previously
      allopatric populations during cooler Pleistocene glacial cycles. Analysis of
      molecular variance indicates that most of the observed genetic variation occurs
      among the four regions implying long-term interruption of maternal gene flow,
      suggesting that L. ailaonicum may represent more than one distinct species and
      should at least be separated into four management units corresponding to these
      four geographic lineages for conservation.

PMID- 19850144
TI  - Genetic analysis of conidiation regulatory pathways in koji-mold Aspergillus
      oryzae.
AB  - Conidia of koji-mold Aspergillus oryzae are often used as starters in the
      fermented food industry. However, little is known about conidiation regulation in
      A. oryzae. To improve the productivity of conidia in A. oryzae, it is necessary
      to understand conidiation regulation in the strain. Therefore, we analyzed the
      conidiation regulatory system in A. oryzae using 10 kinds of conidiation
      regulatory gene disruptants. The phenotypes of AorfluG, AorflbA, AorflbB,
      AorflbC, AorflbD, AorflbE, AorbrlA, AorabaA, AorwetA, and AorfadA mutants are
      almost identical to those of the corresponding mutants in Aspergillus nidulans.
      The results indicated that the functions of conidiation regulatory genes are
      almost conserved between A. oryzae and A. nidulans. However, the severely reduced
      conidiation phenotype of the AorfluG disruptant in A. oryzae differs from the
      phenotype of the corresponding mutant in Aspergillus fumigatus in air-exposed
      culture conditions. These results suggest that A. oryzae, A. nidulans, and A.
      fumigatus have a G-protein signaling pathway and brlA orthologs in common, and
      only A. fumigatus has particular brlA activation pathways that are independent of
      the fluG ortholog. Furthermore, the analyses of AorflbA disruptant and AorfadA
      dominant-active mutants implicated that AorFadA-mediated G-protein signaling
      suppresses vegetative growth of A. oryzae.

PMID- 19850145
TI  - The dst2 gene essential for photomorphogenesis of Coprinopsis cinerea encodes a
      protein with a putative FAD-binding-4 domain.
AB  - The fruiting-body primordium of Coprinopsis cinerea exhibits remarkable
      photomorphogenesis. Under a 12-h light/12-h dark regime, the primordium proceeds
      to the fruiting-body maturation phase in which the primordium successively
      undergoes basidiospore formation, stipe elongation and pileus expansion,
      resulting in the mature fruiting-body. In continuous darkness, however, the
      primordium never proceeds to the maturation phase: the pileus and stipe tissues
      at the upper part of the primordium remain rudimentary while the basal part of
      the primordium elongates, producing the etiolated "dark stipe" phenotype. In our
      previous studies, blind mutants, which produce dark stipes under light conditions
      that promote fruiting-body maturation in the wild-type, have been isolated, and
      two genes, dst1 and dst2, responsible for the mutant phenotype have been
      identified. In this study we show that the dst2-1 mutant exhibits a blind
      phenotype during asexual spore production in addition to that in fruiting-body
      photomorphogenesis. We also reveal that dst2 is predicted to encode a protein
      with a putative flavin adenine dinucleotide (FAD)-binding-4 domain. The two blind
      phenotypes, together with the existence of an FAD-binding domain in Dst2, suggest
      that Dst2 may play a role in perceiving blue light.

PMID- 19850146
TI  - Characterization and expression analysis of a maltose-utilizing (MAL) cluster in
      Aspergillus oryzae.
AB  - Starch and maltooligosaccharides such as maltose and maltotriose induce the
      production of amylolytic enzymes including alpha-amylase in Aspergillus oryzae. A
      transcriptional activator gene amyR, required for maltose induction of amylolytic
      enzymes, has been cloned and characterized. The amyR gene deletion mutant showed
      significantly poor growth on starch medium but normal growth on maltose medium.
      This indicated the existence of another maltose-utilizing system, whose
      expression might not be controlled by amyR. We have identified a gene cluster
      homologous to the MAL cluster of Saccharomyces cerevisiae in the A. oryzae
      genome. The cluster consists of a MAL61 homolog (designated malP), a MAL62
      homolog (designated malT), and a MAL63 homolog (designated malR). Overexpression
      of malT in A. oryzae resulted in a significant increase in intracellular alpha
      glucosidase activity, and that of malP allowed S. cerevisiaemal61Delta to grow on
      maltose. The expression of both malP and malT genes was highly up-regulated in
      the presence of maltose, but malR expressed constitutively irrespective of carbon
      sources. Disruption of malR resulted in the loss of malP and malT expression and
      thus in restricted growth on maltose medium. In addition, a malP disruptant
      showed a significantly reduced expression of malT and malR and exhibited a growth
      defect on maltose similar to the malR disruptant. These results suggest that the
      MAL cluster of A. oryzae is responsible for the assimilation of maltose in A.
      oryzae.

PMID- 19850148
TI  - The role of B cells in lupus pathogenesis.
AB  - Autoantibodies clearly contribute to tissue inflammation in systemic lupus
      erythematosus. In order to therapeutically target B cells making pathogenic
      autoantibodies, it is necessary to identify their phenotype. It is also important
      to understand the defects in B cell repertoire selection that permit pathogenic
      autoreactive B cells to enter the immunocompetent B cell repertoire. We present
      the data that both marginal zone and follicular B cells can produce pathogenic
      autoantibodies. Moreover, we discuss how B cell survival and maturation are
      regulated centrally prior to antigen activation and in the periphery after
      antigen activation to form the repertoire that generates the spectrum of
      circulating antibodies.

PMID- 19850147
TI  - Fibrocytes: bringing new insights into mechanisms of inflammation and fibrosis.
AB  - Regeneration and fibrosis are integral parts of the recovery process following
      tissue injury, and impaired regulation of these mechanisms is a hallmark of many
      chronic diseases. A population of bone marrow-derived mesenchymal progenitor
      cells known as fibrocytes, play an important role in tissue remodeling and
      fibrosis in both physiologic and pathologic settings. In this review we summarize
      the key concepts regarding the pathophysiology of wound healing and fibrosis, and
      present data to support the contention that circulating fibrocytes are important
      in both normal repair process and aberrant healing and fibrotic damage associated
      with a diverse set of disease states.

PMID- 19850150
TI  - MeSHing molecular sequences and clinical trials: a feasibility study.
AB  - The centralized and public availability of molecular sequence and clinical trial
      data presents an opportunity to identify potentially valuable linkages across the
      bench-to-bedside "T1" translational barrier. In this study, we sought to leverage
      keyword metadata (Medical Subject Heading [MeSH] descriptors) to infer
      relationships between molecular sequences and clinical trials, as indexed by
      GenBank and ClinicalTrials.gov. The results of this feasibility study found that
      approximately 30% of sequences in GenBank could be linked to trials and over 90%
      of trials in ClinicalTrials.gov could be linked to sequences through MeSH
      descriptors. In a cursory evaluation, we were able to consistently identify
      meaningful linkages between molecular sequences and clinical trials. Based on our
      findings, there may be promise in subsequent studies aiming to identify linkages
      across the T1 translational barrier using existing large repositories.

PMID- 19850149
TI  - Forkhead transcription factors in chronic inflammation.
AB  - Forkhead (Fox) transcription factors have been increasingly recognized to play
      key roles in immune homeostasis, especially Foxp3 for its role in the development
      and function of regulatory T cells, and Foxo family members for their regulatory
      role in T and B lymphocytes as well as other leukocytes. Although these
      transcription factors positively regulate the expression of multiple target
      genes, a unique functional attribute of these genes is the maintenance of
      leukocyte homeostasis, such as the preservation of the naive or quiescent T cell
      state and prevention of autoimmunity. As a result, many chronic inflammatory
      processes appear to reflect a relative loss of activity of one of these
      transcription factors, raising the possibility that therapeutic approaches which
      confer gain-of-function Fox activity may be beneficial. On the other hand,
      however, some of the Fox family members also appear to promote and/or maintain
      chronic inflammation by preserving inflammatory leukocyte survival and/or
      otherwise promoting the expression of inflammatory target genes, at least in some
      cell types such as neutrophils. Therefore, although the role of Fox in
      inflammatory disorders remains complex and incompletely understood, the continued
      study of these factors provides new insight into the initiation, maintenance, and
      propagation of inflammation.

PMID- 19850151
TI  - Regulation of arteriolar density in adult myocardium during low thyroid
      conditions.
AB  - Low thyroid function induced by either propylthiouracil (PTU) treatment or
      thyroidectomy surgery led to a reduction of arteriolar density in adult rat
      myocardium, which can be prevented by treatment with thyroxine or the thyroid
      hormone analogue 3,5-diiodothyropropionic acid (DITPA). However, many questions
      related to pathophysiological changes and the regulation of arteriolar density in
      the heart due to hypothyroidism remain unanswered. Sprague-Dawley rats were
      treated with PTU in drinking water for 1, 3, and 6weeks, or co-treated with the
      vasodilator dipyridamole and PTU for 6weeks, or treated with PTU for 6weeks and
      treatment discontinued for 2 or 4weeks. Heart mass, body mass, cardiac function
      and myocardial arteriolar density were determined. Arteriolar loss in
      hypothyroidism induced by PTU treatment progressed gradually with a 22% reduction
      after 3weeks treatment and 34% by 6weeks which was largely reversed after
      discontinuing PTU treatment for only 2weeks. Combined treatment with the
      vasodilator dipyridamole during the 6-week PTU treatment period prevented vessel
      loss indicating the mechanism of arteriolar loss from hypothyroidism may result
      from vasoconstriction. These results suggest that thyroid hormone is a powerful
      regulator of vasculature in adult myocardium, particularly in low thyroid states.

PMID- 19850152
TI  - Thyroid hormones and cardiac arrhythmias.
AB  - Thyroid hormone plays an important role in cardiac electrophysiology and Ca2+
      handling through both genomic and nongenomic mechanisms of action, while both
      actions can interfere. Chronic changes in the amount of circulating thyroid
      hormone due to thyroid dysfunction or systemic disease result in structural,
      electrophysiological and Ca2+ handling remodeling, while acute changes may affect
      basal activity of cardiac cells membrane systems. Consequently, long-term or
      rapid modulation of sarcolemmal ion channels, Ca2+ cycling proteins and
      intercellular communicating channels by thyroid hormone may affect heart function
      as well as susceptibility of the heart to arrhythmias. This aspect including pro-
      and anti-arrhythmic potential of thyroid hormone is highlighted in this review.

PMID- 19850153
TI  - Personality traits and impaired health-related quality of life in patients with
      functional gastrointestinal disorders.
AB  - BACKGROUND & AIMS: Negative affectivity and social isolation (Type D personality)
      are personality traits associated with poor health-related quality of life
      (HRQoL). We hypothesized these traits would be associated with impaired HRQoL and
      increased gastrointestinal symptom severity in functional gastrointestinal
      disorders. METHODS: Data were collected from patients undergoing breath testing.
      Patients completed the Type D Scale-14, Gastrointestinal Symptoms Severity Index
      and Short-Form Health Survey 12. RESULTS: Of 230 patients evaluated, 37% met
      criteria for Type D personality. Type D was associated with a decreased Mental
      Component score on the Short-Form Health Survey 12 (mean difference = -8.29; 95%
      confidence interval, 5.2-11.4; P < .001). On the Gastrointestinal Symptoms
      Severity Index, severity of symptoms was significantly higher in Type D patients
      compared with non Type D patients (P < .001). CONCLUSIONS: Type D personality was
      associated with decreased perceived HRQoL and reporting of more severe
      gastrointestinal symptoms. Type D personality construct may be an important
      consideration when assessing HRQoL outcomes. Consideration of personality traits
      could improve risk stratification in research and clinical practice in this
      patient group.

PMID- 19850156
TI  - Risk of esophageal adenocarcinoma and mortality in patients with Barrett's
      esophagus: a systematic review and meta-analysis.
AB  - BACKGROUND & AIMS: As the risk of esophageal adenocarcinoma (EAC) and mortality
      in patients with Barrett's esophagus (BE) are important determinants of the
      potential yield and cost-effectiveness of BE surveillance, clarification of these
      factors is essential. We therefore performed a systematic review and meta
      analysis to determine the incidence of EAC and mortality due to EAC in BE under
      surveillance. METHODS: Databases were searched for relevant cohort studies in
      English language that reported EAC risk and mortality due to EAC in BE. Studies
      had to include patients with histologically proven BE, documented follow-up, and
      histologically proven EAC on surveillance. A random effects model was used with
      assessment of heterogeneity by the I(2)-statistic and of publication bias by
      Begg's and Egger's tests. RESULTS: Fifty-one studies were included in the main
      analysis. The overall mean age of BE patients was 61 years; the mean overall
      proportion of males was 64%. The pooled estimate for EAC incidence was 6.3/1000
      person-years of follow-up (95% confidence interval, 4.7-8.4) with considerable
      heterogeneity (P < .001; I(2) = 79%). Nineteen studies reported data on mortality
      due to EAC. The pooled incidence of fatal EAC was 3.0/1000 person-years of follow
      up (95% confidence interval, 2.2-3.9) with no evidence for heterogeneity (P = .4;
      I(2) = 7%). No evidence of publication bias was found. CONCLUSIONS: Patients with
      BE are at low risk of malignant progression and predominantly die due to causes
      other than EAC. This undermines the cost-effectiveness of BE surveillance and
      supports the search for valid risk stratification tools to identify the minority
      of patients that are likely to benefit from surveillance.

PMID- 19850154
TI  - Serious complications within 30 days of screening and surveillance colonoscopy
      are uncommon.
AB  - BACKGROUND & AIMS: The risk of serious complications after colonoscopy has
      important implications for the overall benefits of colorectal cancer screening
      programs. We evaluated the incidence of serious complications within 30 days
      after screening or surveillance colonoscopies in diverse clinical settings and
      sought to identify potential risk factors for complications. METHODS: Patients
      age 40 and over undergoing colonoscopy for screening, surveillance, or evaluation
      based an abnormal result from another screening test were enrolled through the
      National Endoscopic Database (CORI). Patients completed a standardized telephone
      interview approximately 7 and 30 days after their colonoscopy. We estimated the
      incidence of serious complications within 30 days of colonoscopy and identified
      risk factors associated with complications using logistic regression analyses.
      RESULTS: We enrolled 21,375 patients. Gastrointestinal bleeding requiring
      hospitalization occurred in 34 patients (incidence 1.59/1000 exams; 95%
      confidence interval [CI], 1.10-2.22). Perforations occurred in 4 patients
      (0.19/1000 exams; 95% CI, 0.05-0.48), diverticulitis requiring hospitalization in
      5 patients (0.23/1000 exams; 95% CI, 0.08-0.54), and postpolypectomy syndrome in
      2 patients (0.09/1000 exams; 95% CI, 0.02-0.30). The overall incidence of
      complications directly related to colonoscopy was 2.01 per 1000 exams (95% CI,
      1.46-2.71). Two of the 4 perforations occurred without biopsy or polypectomy. The
      risk of complications increased with preprocedure warfarin use and performance of
      polypectomy with cautery. CONCLUSIONS: Complications after screening or
      surveillance colonoscopy are uncommon. Risk factors for complications include
      warfarin use and polypectomy with cautery.

PMID- 19850157
TI  - Dynamic expression of the TRPM subgroup of ion channels in developing mouse
      sensory neurons.
AB  - Despite the significance of transient receptor potential (TRP) channels in
      sensory physiology, little is known of the expression and developmental
      regulation of the TRPM (melastatin) subgroup in sensory neurons. In order to find
      out if the eight TRPM subgroup members (TRPM1-TRPM8) have a possible role in the
      sensory nervous system, we characterized the developmental regulation of their
      expression in mouse dorsal root ganglion (DRG) from embryonic (E) day 12 to
      adulthood. Transcripts for all channels except for TRPM1 were detected in lumbar
      and thoracic DRG and in nodose ganglion (NG) with distinguishable expression
      patterns from E12 until adult. For most channels, the expression increased from
      E14 to adult with the exception of TRPM5, which displayed transient high levels
      during embryonic and early postnatal stages. Cellular localization of TRPM8 mRNA
      was found only in a limited subset of very small diameter neurons distinct in
      size from other populations. These neurons did not bind isolectin B4 (IB4) and
      expressed neither the neuropeptide calcitonin gene-related peptide (CGRP) nor
      neurofilament (NF)200. This suggests that TRPM8(+) thermoreceptive sensory
      neurons fall into a separate group of very small sized neurons distinct from
      peptidergic and IB4(+) subtypes of sensory neurons. Our results, showing the
      expression and dynamic regulation of TRPM channels during development, indicate
      that many TRPM subfamily members could participate during nervous system
      development and in the adult by determining distinct physiological properties of
      sensory neurons.

PMID- 19850158
TI  - Sleeve lobectomy for patients with non-small cell lung cancer.
AB  - PURPOSE: A sleeve lobectomy for lung cancer is a procedure intended both for the
      maintenance of lung function and for radical treatment. We investigated the
      clinico-pathological features and treatment responses of lung cancer patients who
      underwent sleeve lobectomy in our department. SUBJECTS: Among the 984 patients
      with non-small cell lung cancer who underwent resection in our department between
      1994 and 2007, the subjects were 24 patients in whom a sleeve lobectomy was
      performed. RESULTS: There were 18 male and 6 female patients, with a mean age of
      65 years. The histological type was diagnosed as squamous cell carcinoma in 14
      patients, and adenocarcinoma in 10. Patients with either mucoepidermoid carcinoma
      (n=1) or carcinoid tumor (n=1) were excluded. The pathological stage was
      evaluated as IA, IB, II, IIIA, IIIB, and IV in 4, 1, 8, 8, 2, and 1 patient,
      respectively. Regarding post-operative complications, 4 patients required sputum
      aspiration with a bronchoscope from the 2nd to 7th post-operative day due to
      sputum retention. The 5-year survival rate in patients who underwent sleeve
      lobectomy was 70.0%. According to the pathological nodal status, the 5-year
      survival rates of N0, N1, and N2 were 100.0%, 87.5%, and 41.7%, respectively. The
      5-year survival rates in squamous cell carcinoma and adenocarcinoma were 83.0%
      and 45.7%, respectively. CONCLUSION: Sleeve lobectomy facilitated the maintenance
      of residual lung function without serious perioperative complications. This
      finding suggests that patients with direct tumor invasion to the bronchus might
      be good candidates for a sleeve lobectomy, but not those with extra-nodal
      invasion.

PMID- 19850159
TI  - Proteomic analysis in NSAIDs-treated primary cardiomyocytes.
AB  - NSAIDs (non-steroidal anti-inflammatory drugs) are widely used for the treatment
      of a variety of inflammatory diseases, but many of them were withdrawn from the
      market due to their cardiovascular toxicity. In this study, we tried to identify
      proteins responding to the cellular toxicity in NSAIDs-treated primarily cultured
      cardiomyocytes using 2-D proteomic analysis. We used seven different NSAIDs
      (celecoxib, rofecoxib, valdecoxib, diclofenac, naproxen, ibuprofen, and
      meloxicam) possessing each different degree of cardiovascular risk. Overall
      protein spots were similar in all NSAIDs-treated cells although numbers of
      decreased proteins were about 2-fold higher in celecoxib or rofecoxib-treated
      cells than in cells incubated with other NSAIDs. Many stress-related proteins,
      cardiac muscle movement proteins and proteins involved in membrane organization
      have been isolated. Among them, Septin-8, a filament scaffolding protein, showed
      its specific expression pattern depending on the extent of drug toxicity. Its
      expression level was low in cells treated by relatively high toxic drugs such as
      celecoxib, diclofenac, valdecoxib, and rofecoxib. On the contrary, Septin-8 was
      similarly expressed in control cells in the presence of less toxic drugs such
      ibuprofen, naproxen, and meloxicam. This data suggests that Septin-8
      differentially responds to each NSAID.

PMID- 19850161
TI  - Comparative analysis of the electrostatics of the binding of cationic proteins to
      vesicles: asymmetric location of anionic phospholipids.
AB  - The role of electrostatics is studied in the adsorption of cationic proteins to
      zwitterionic phosphatidylcholine (PC) and anionic PC/phosphatidylglycerol (PG)
      mixed small unilamellar vesicles (SUVs). For model proteins the interaction is
      monitored vs. PG content at low ionic strength. The adsorption of lysozyme and
      myoglobin (isoelectric point, pI 7-11) is investigated in SUVs, along with
      changes of the fluorescence emission spectra of the cationic proteins, via their
      adsorption on SUVs. In the Gouy-Chapman formalism, the activity coefficient goes
      with the square of charge number. Deviations from the ideal model could indicate
      the asymmetric location of the anionic phospholipid in the bilayer inner leaflet,
      in mixed zwitterionic/anionic SUVs for both lysozyme- and myoglobin-PC/PG
      systems, in agreement with experiments and molecular dynamics simulations. Fitted
      effective SUV charge stays constant. Effective-formal difference increases 0.417
      e.u. Effective protein charge increases as PC/PG<PC being greater for myoglobin.
      The molar free energies of the protein in aqueous and lipid phases increase as
      PC<PC/PG. Both free-energy changes are greater for myoglobin. Effective
      interfacial charge stays constant for anionic PC/PG SUVs being greater for
      myoglobin.

PMID- 19850162
TI  - Characterization of the morphology of co-extruded, thermoplastic/rubber multi
      layer tapes.
AB  - Tapes with alternating semi-crystalline thermoplastic/rubber layers with
      thicknesses varying from 100 nm up to several microm were prepared by multi-layer
      co-extrusion. The variation in layer thickness was obtained by varying the
      thermoplastic/rubber feed ratio. A systematic study on the use of various
      microscopy techniques to visualize the morphology of the layered systems is
      presented. The relatively large length scales and the sample preparation make
      optical microscopy (OM) unsuitable to study the morphology of the multi-layer
      tapes. Although excellent contrast between the thermoplastic and rubber layers
      can be obtained, the usually applied, relatively large magnifications limit the
      use of transmission electron microscopy (TEM) and atomic force microscopy (AFM)
      to small sample areas. The large range of applicable magnifications makes
      scanning electron microscopy (SEM) the most suitable technique to study the
      morphology of the multi-layer tapes. The sample preparation for SEM with a
      secondary electron (SE) detector is often based on the removal of one of the
      components, which may induce changes in the morphology. SEM with a back-scattered
      electron (BSE) detector is a very convenient method to study the morphology over
      a wide range of length scales, where the contrast between the different layers
      can be enhanced by chemical staining. Finally, the nucleation behavior
      (homogeneous versus heterogeneous) of the semi-crystalline layers, as probed by
      differential scanning calorimetry (DSC), provides valuable information on the
      layered morphology. The use of relatively straightforward DSC measurements shows
      a clear advantage with respect to the discussed microscopy techniques, since no
      sample preparation is required and relatively large samples can be studied, which
      are more representative for the bulk.

PMID- 19850163
TI  - Rapid methods of polymer and polymer additives identification: multi-sample
      solvent-free MALDI, pyrolysis at atmospheric pressure, and atmospheric solids
      analysis probe mass spectrometry.
AB  - Polymer manufacturers add antioxidants, waxes, dyes, and other materials to
      enhance polymer utility or processing. Numerous analytical methods are available
      to characterize various chemical aspects of polymers including methods interfaced
      with mass spectrometry (MS) such as pyrolysis (Py), gas chromatography (GC),
      liquid chromatography (LC), and thermogravimetric analysis (TGA). Current methods
      work well, but because of the necessity of extraction, chromatography, or thermal
      methods, most are too time consuming for high throughput analyses which might be
      necessary in, for example, regulatory laboratories. Here we discuss three MS
      methods for rapid analysis of polymers; multi-sample MALDI MS which allows rapid
      analysis of low molecular weight polymers, atmospheric pressure (AP) solids
      analysis probe MS for direct ambient additives analysis, and APPy MS for polymer
      identification. The latter methods provide information regardless of the
      composition or molecular weight of the polymeric material.

PMID- 19850164
TI  - Characterisation of archaeological waterlogged wood by pyrolytic and mass
      spectrometric techniques.
AB  - Two techniques based on analytical pyrolysis and mass spectrometry, direct
      exposure-MS (DE-MS) and pyrolysis-gas chromatography/mass spectrometry (Py
      GC/MS), were used to characterise waterlogged archaeological wood and to study
      degradation patterns of wood in aqueous environments. The two techniques were
      applied to samples from the excavation of the Site of the Ancient Ships of Pisa
      San Rossore in Pisa (Italy), and data were compared to those relative to native
      sound wood of the same species (pine, elm, beech). Both the methods result
      valuable in the analysis of ancient wood artefacts, avoiding the long wet
      chemical procedures that are commonly used in wood analysis, and allowing us to
      use a minimal sample size. DE-MS achieves a global mass spectral fingerprint of
      lignin and polysaccharides pyrolysis compounds in few minutes, and the results
      have been interpreted with the support of principal component analysis (PCA) of
      mass spectra. Py-GC/MS permits detailed molecular analysis of pyrolysis compounds
      and highlights some chemical modifications of lignin in archaeological samples,
      as demethylation of both guaiacyl and syringyl lignin units. Both the techniques
      demonstrate consistent loss of polysaccharides in archaeological wood.

PMID- 19850165
TI  - Non-invasive analysis of swelling in polymer dispersions by means of time
      domain(TD)-NMR.
AB  - In this contribution, we discuss the potential of low-field time-domain(TD)-NMR
      to study the swelling of (aqueous) polymer dispersions by a volatile solvent. Due
      to the sensitivity of transverse relaxation times (T2) to swelling-induced
      changes in the molecular dynamics of the polymer component, the effects of
      swelling can be measured without spectral resolution. The measurement is
      performed on polymer dispersions in native state with solids contents around 50%
      in a non-invasive way without separating the polymeric phase and the water phase
      from each other. Using acetone in two polyurethane (PU) dispersions with
      different hard phase contents, we explore the sensitivity of the method and
      present a data evaluation strategy based on multicomponent fitting and proton
      balancing. Furthermore, we report exchange continualization as a further effect
      that needs to be taken into account for correct interpretation of the data.

PMID- 19850166
TI  - Identification and quantification of polycarboxylates in detergent products using
      off-line size exclusion chromatography-nuclear magnetic resonance.
AB  - The performance of many contemporary detergent products critically depends on
      polymers. Water-soluble polycarboxylates represent an important class of
      detergent polymers, and their quantitative assessment in detergent matrices
      stands as a considerable challenge. The presence of high levels of surfactants is
      a major complication, due to the strong tendency of surfactants to form micelles
      and to interact with the polymers. First, we addressed critical steps in the
      subsequent combined use of liquid extraction and off-line size exclusion
      chromatography-nuclear magnetic resonance (SEC-NMR) for identification and
      quantification of polycarboxylates in detergent products. Next, the different
      steps in the off-line SEC-NMR procedure were optimized with respect to precision
      and accuracy. This resulted in recoveries of more than 80% for maleic
      acid/acrylic acid copolymers; in detergent products a proportional bias of 30% is
      achieved. The method showed good precision with a relative standard deviation of
      within-laboratory reproducibility between 5% and 14%.

PMID- 19850167
TI  - Improved compositional analysis of block copolymers using diffusion ordered NMR
      spectroscopy.
AB  - Block copolymers constitute a fascinating class of polymeric materials that are
      used in a broad range of applications. The performance of these materials is
      highly coupled to the physical and chemical properties of the constituting block
      copolymers. Traditionally, the composition of block copolymers is obtained by 1H
      NMR spectroscopy on purified copolymer fractions. Specifically, the integrals of
      a properly selected set of 1H resonances are compared and used to infer the
      number average molecular weight (M(n)) of one of the block from the (typically
      known) M(n) value of the other. As a corollary, compositional determinations
      achieved on imperfectly purified samples lead to serious errors, especially when
      isolation of the block copolymer from the initial macro initiator is tedious.
      This investigation shows that Diffusion Ordered NMR Spectroscopy (DOSY) can be
      used to provide a way to assess the advancement degree of the copolymerization
      purification/reaction, in order to optimize it and hence contribute to an
      improved compositional analysis of the resulting copolymer. To this purpose, a
      series of amphiphilic polystyrene-b-poly(ethylene oxide) block copolymers,
      obtained by controlled free-radical nitroxide mediated polymerization, were
      analyzed and it is shown that, under proper experimental conditions, DOSY allows
      for an improved compositional analysis of these block copolymers.

PMID- 19850168
TI  - Structural characterization of a poly(methacrylic acid)-poly(methyl methacrylate)
      copolymer by nuclear magnetic resonance and mass spectrometry.
AB  - Mass spectrometry (MS) and nuclear magnetic resonance (NMR) have been combined to
      achieve the complete microstructural characterization of a poly(methacrylic acid)
      poly(methyl methacrylate) (PMAA-PMMA) copolymer synthesized by nitroxide-mediated
      polymerization. Various PMAA-PMMA species could be identified which mainly differ
      in terms of terminaisons. 1H and 13C NMR experiments revealed the structure of
      the end-groups as well as the proportion of each co-monomer in the copolymers.
      These end-group masses were further confirmed from m/z values of doubly charged
      copolymer anions detected in the single stage mass spectrum. In contrast,
      copolymer composition derived from MS data was not consistent with NMR results,
      obviously due to strong mass bias well known to occur during electrospray
      ionization of these polymeric species. Tandem mass spectrometry could reveal the
      random nature of the copolymer based on typical dissociation reactions, i.e.,
      water elimination occurred from any two contiguous MAA units while MAA-MMA pairs
      gave rise to the loss of a methanol molecule. Polymer backbone cleavages were
      also observed to occur and gave low abundance fragment ions which allowed the
      structure of the initiating end-group to be confirmed.

PMID- 19850169
TI  - Identification and quantitation of trace impurities in fatty alcohol ethoxylates
      using HPLC and MALDI-TOF mass spectrometry.
AB  - A two-step HPLC separation that combines isocratic and gradient elution has been
      developed for the analysis of trace impurities in fatty alcohol ethoxylates
      (FAEs). Quantitative estimates of the early eluting impurities were obtained from
      a calibration curve based on the responses of an evaporative light scattering
      detector (ELSD). Isocratic conditions were used to elute the impurities and
      gradient conditions for the main FAE components. In this manner, an acceptable
      compromise was obtained between resolution and analysis time. Fractions were
      collected and the impurities identified using MALDI-TOF mass spectrometry.

PMID- 19850170
TI  - Enzymatic determination of cholesterol and triglycerides in serum lipoprotein
      profiles by asymmetrical flow field-flow fractionation with on-line, dual
      detection.
AB  - Alterations of lipoproteins (LPs) and related lipid levels in blood serum are
      correlated to the risk of coronary artery disease (CAD). Fast, possibly automated
      methods to obtain complete, multi-parametric LP profiles are therefore welcome to
      be developed for routine, clinical analysis practice. In this work, asymmetrical
      flow field-flow fractionation (AF4) with on-line, dual post-fractionation
      reaction detection (PFRD) is applied to develop a method for single-run,
      simultaneous quantification of cholesterol (CHOL) and triglycerides (TGs) in each
      fractionated LP class. The enzymatic reagents used for the post-fractionation
      reaction are available as commercial kits for certified, standard clinical
      protocols for the analysis of CHOL and TGs in serum. Using CHOL and glycerol as
      reference standards, a new procedure is applied to optimize the experimental
      conditions for PFRD-based, quantitative analysis. Upon optimized PFRD and AF4
      conditions, results obtained for the determination of total CHOL (TC), TGs, HDL
      cholesterol (HDL-C), and LDL-cholesterol (LDL-C) in a set of serum samples from
      healthy donors are found in agreement with the values provided by a clinical
      laboratory. The intra-day and inter-day precisions of the method were found
      always lower than 10% (CV). When the method was applied to serum samples from
      patients affected by sepsis, differences in CHOL and TG profiles between patients
      and healthy donors were observed.

PMID- 19850171
TI  - Comparison of adsorption equilibrium of fructose, glucose and sucrose on
      potassium gel-type and macroporous sodium ion-exchange resins.
AB  - Adsorption equilibrium of fructose, glucose and sucrose was evaluated on
      sulfonated poly(styrene-co-divinylbenzene) cation-exchange resins. Two types of
      resins were used: potassium (K+) gel-type and sodium (Na+) macroporous resins.
      Influence of the cation and effect of the resin structure on adsorption were
      studied. The adsorption isotherms were determined by the static method in batch
      mode for mono-component and multi-component sugar mixtures, at 25 and 40 degrees
      C, in a range of concentrations between 5 and 250 g L(-1). All adsorption
      isotherms were fitted by a linear model in this range of concentrations. Sugars
      were adsorbed in both resins by the following order: fructose > glucose >
      sucrose. Sucrose was more adsorbed in the Na+ macroporous resin, glucose was
      identically adsorbed, and fructose was more adsorbed in the K+ gel-type resin.
      Data obtained from the adsorption of multi-component mixtures as compared to the
      mono-component ones showed a competitive effect on the adsorption at 25 degrees
      C, and a synergetic effect at 40 degrees C. The temperature increase conducted to
      a decrease on the adsorption capacity for mono-component sugar mixtures, and to
      an increase for the multi-component mixtures. Based on the selectivity results,
      K+ gel-type resin seems to be the best choice for the separation of fructose,
      glucose and sucrose, at 25 degrees C.

PMID- 19850172
TI  - Optimal gradient operation in comprehensive liquid chromatography x liquid
      chromatography systems with limited orthogonality.
AB  - A novel strategy is described for designing optimal second dimension (2D)
      gradient conditions for a comprehensive two-dimensional liquid chromatography
      system where the two dimensions are not fully orthogonal. Using the approach
      developed here, the initial and final organic modifier content values resulting
      in the highest coverage of separation space can be derived for each 2D gradient
      run. Theory indicates that these values can be determined by adapting 2D gradient
      operation to the degree of orthogonality. The new method is tested on a
      comprehensive two-dimensional liquid chromatography system that uses reversed
      phase (RP) columns showing different selectivities in the two dimensions. A
      comparison between analyses carried out using normal and optimized 2D gradients
      showed that the latter allow a more efficient use of analysis time. This can
      result either in an improved peak capacity or in decreasing total analysis time,
      depending on the final goal of the experiment. In the latter scenario, the number
      of separated peaks is comparable to that obtained using gradients spanning a wide
      range of organic modifier but, now, in half the time. As test samples complex
      mixtures of peptides were analyzed.

PMID- 19850174
TI  - A rapid separation method for gel content determination in pressure sensitive
      adhesive dispersions and acrylic-based latices for an industrial setting.
AB  - A rapid method has been developed for determining gel content in industrial
      samples such as water-borne pressure sensitive adhesives (PSAs) and acrylic-based
      latices. The method is based on thermal field-flow fractionation (ThFFF) and
      evaporative light scattering detection (ELSD). Results are compared to those
      obtained using a centrifugation-based gravimetric method. Sample preparation was
      an important aspect of the developed analysis. Although the latices and PSA are
      similar in chemistry, they required different handling and sample preparation
      procedures. The PSA sample, with its sub-ambient glass transition temperature
      (Tg), formed visible macro-gels, if it was added directly to tetrahydrofuran
      (THF). No macro-gels were formed, if the PSA was pre-diluted in water and then
      suspended in THF. By using this new sample preparation procedure and ThFFF total
      analysis time was reduced from days to a few hours. The gel content in water
      borne pressure sensitive adhesives and acrylic-based latices varied from 5 to 51%
      with an average relative standard deviation (RSD) of 11%.

PMID- 19850173
TI  - Fractionation of human serum lipoproteins and simultaneous enzymatic
      determination of cholesterol and triglycerides.
AB  - A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to
      separate different types of lipoproteins from human serum. The emphasis in the
      method optimization was on the possibilities to characterize the largest
      lipoprotein fractions (LDL and VLDL), which is usually not possible with the size
      exclusion chromatography methods applied in routine analysis. Different channel
      geometries and flow programs were tested and compared. The use of a short
      fractionation channel was shown to give less sample dilution at the same
      fractionation power compared to a conventional, long channel. Different size
      selectivities were obtained with an exponential decay and a linear cross flow
      program. The ratio of the UV absorption signal to the light scattering signal was
      used to validate the relation between retention time and size of the fractionated
      particles. An experimental setup was developed for the simultaneous determination
      of the cholesterol and triglycerides distribution over the lipoprotein fractions,
      based on enzymatic reactions followed by UV detection at 500 nm. Coiled and
      knitted PTFE tubing reactors were compared. An improved peak sharpness and
      sensitivity were observed with the knitted tubing reactor. After optimization of
      the experimental conditions a satisfactory linearity and precision (2-3% rsd for
      cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum
      samples, a pooled sample from healthy volunteers and samples of sepsis patients,
      were analyzed with the method developed. Lipoprotein fractionation and
      cholesterol and triglyceride distributions could be correlated with the clinical
      background of the samples.

PMID- 19850175
TI  - To know, to reason, to act.

PMID- 19850176
TI  - Trust, power, and vulnerability: a discourse on helping in nursing.
AB  - This article uses philosophical inquiry to present the relationship between the
      helping role in nursing and the concept of trust essential to it. It
      characterizes helping as the moral center of the nurse-patient relationship and
      discusses how patients' expectations of help and caring create obligations of
      trustworthiness on the part of the nurse. It uses literature from various
      disciplines to examine different theoretical accounts of trust, each presenting
      important features of trust relationships that apply to health care
      professionals, patients, and families. Exploring the concept of trust, and the
      key leverage points that elicit it, develops a thesis that nurses can improve
      their understanding of the principal attributes and the conditions that foster or
      impede trust. The article concludes that trust is the core moral ingredient of
      helping relationships. Trust as a moral value is even more basic than duties of
      beneficence, respect, veracity, and autonomy. Trust is the confident expectation
      that others can be relied upon to act with good will and to secure what is best
      for the person seeking help.

PMID- 19850177
TI  - Personal conscience and the problem of moral certitude.
AB  - The moral practice of nursing requires the difficult work of discerning the best
      response to an ethical quandary. Determining the right course of action can
      rarely be discovered by assuming that one value, one theory, one point of view
      will always and reliably identify the morality of an action. Thus, the role of a
      nurse is an inherently moral activity that is at the heart and soul of health
      care. Practitioners who move too quickly to a state of moral certainty about a
      decision may be missing essential components of the enactment of moral agency.
      Personal integrity and professional integrity, patient interests, society's
      expectation of a profession, the balance between rights and obligations within
      the nurse-patient relationship, acting according to one's conscience, power,
      control, and moral certainty are a few of the topics that enrich thinking about
      the moral richness of nursing practice, and will encourage readers to know, to
      reason, and to act in ways that demonstrate reflective moral judgment.

PMID- 19850178
TI  - Art, science, or both? Keeping the care in nursing.
AB  - Nursing is widely considered as an art and a science, wherein caring forms the
      theoretical framework of nursing. Nursing and caring are grounded in a relational
      understanding, unity, and connection between the professional nurse and the
      patient. Task-oriented approaches challenge nurses in keeping care in nursing.
      This challenge is ongoing as professional nurses strive to maintain the concept,
      art, and act of caring as the moral center of the nursing profession. Keeping the
      care in nursing involves the application of art and science through theoretical
      concepts, scientific research, conscious commitment to the art of caring as an
      identity of nursing, and purposeful efforts to include caring behaviors during
      each nurse-patient interaction. This article discusses the profession of nursing
      as an art and a science, and it explores the challenges associated with keeping
      the care in nursing.

PMID- 19850179
TI  - Moral accountability and integrity in nursing practice.
AB  - The therapeutic nature of the nurse-patient relationship is grounded in an ethic
      of caring. Florence Nightingale envisioned nursing as an art and a science...a
      blending of humanistic, caring presence with evidence-based knowledge and
      exquisite skill. In this article, the author explores the caring practice of
      nursing as a framework for understanding moral accountability and integrity in
      practice. Being morally accountable and responsible for one's judgment and
      actions is central to the nurse's role as a moral agent. Nurses who practice with
      moral integrity possess a strong sense of themselves and act in ways consistent
      with what they understand is the right thing to do. A review of the literature
      related to caring theory, the concepts of moral accountability and integrity, and
      the documents that speak of these values and concepts in professional practice
      (eg, Code of Ethics for Nurses with Interpretive Statements, Nursing's Social
      Policy Statement) are presented in this article.

PMID- 19850180
TI  - Nursing advocacy in a postgenomic age.
AB  - The Human Genome Project will change how health is defined and how disease is
      prevented, diagnosed, and treated. As the largest group of health care providers
      in contact with patients, nurses need to be competent in the science of genetics.
      Beyond this, nurses need to understand the complexities that arise in genomic
      health care. Ethical, legal, and social issues are integral to the delivery of
      genomic health care, and nurses must have an astute understanding of such
      complexities. What it means to know, to reason, and to act in this postgenomic
      age is explored.

PMID- 19850181
TI  - Healing during existential moments: the "art" of nursing presence.
AB  - This article addresses nursing presence, a phenomenon essential to holistic
      nursing care. The concept is introduced and explained, supporting background
      information is reviewed, barriers are identified, and successful applications are
      illustrated in different clinical settings. Avowing that metaphysical knowledge
      is the underpinning to the art of nursing presence, a Transformative Nursing
      Presence Model is offered as a distinctive framework for nurses and organizations
      interested in fostering enhanced nursing presence.

PMID- 19850182
TI  - Thoughtful nursing practice: reflections on nurse delegation decision-making.
AB  - This article discusses delegation challenges and legal and regulatory oversight
      associated with delegation in the clinical practice setting. The authors address
      moral and legal attributes of the roles and responsibilities of health care
      providers regarding delegating health care interventions. The article also
      explores guiding principles and rules of delegation within professional
      standards, national practice guidelines, and state nurse practice acts. Nurse
      experts provide thoughtful reflection on nursing models and the role of
      delegation, emphasizing the critical role of delegation in extending the role of
      the health care professional in patient care services.

PMID- 19850183
TI  - Science, technology, and innovation: nursing responsibilities in clinical
      research.
AB  - Clinical research is a systematic investigation of human biology, health, or
      illness involving human beings. It builds on laboratory and animal studies and
      often involves clinical trials, which are specifically designed to test the
      safety and efficacy of interventions in humans. Nurses are critical to the
      conduct of ethical clinical research and face clinical, ethical, and regulatory
      challenges in research in many diverse roles. Understanding and addressing the
      ethical challenges that complicate clinical research is integral to upholding the
      moral commitment that nurses make to patients, including protecting their rights
      and ensuring their safety as patients and as research participants.

PMID- 19850184
TI  - Care and meaning in war zone nursing.
AB  - During the past century, nurses have served as caregivers for United States
      military personnel in every major theater of war. Military nurses in the war zone
      deliver patient care while working in austere conditions, and are under constant
      threat of personal danger. This article gives a historical overview of the role
      of nurses in war zones, followed by a review from the perspectives of
      environment, safety, the nature of injuries, and treatment of military personnel
      and civilians.

PMID- 19850185
TI  - Perspectives on transcultural care.
AB  - Culture has been defined as the thoughts, communications, actions, customs,
      beliefs, values, and institutions of racial, ethnic, religious, or social groups.
      A culture of nursing refers to the learned and transmitted lifeways, values,
      symbols, patterns, and normative practices of members of the nursing profession
      of a particular society. To serve the unique and diverse needs of patients in the
      United States, it is imperative that nurses understand the importance of cultural
      differences by valuing, incorporating, and examining their own health-related
      values and beliefs and those of their health care organizations, for only then
      can they support the principle of respect for persons and the ideal of
      transcultural care.

PMID- 19850186
TI  - From means to ends: artificial nutrition and hydration.
AB  - The withdrawal, withholding, or implementation of life-sustaining treatments such
      as artificial nutrition and hydration challenge nurses on a daily basis. To meet
      these challenges, nurses need the composite skills of moral and ethical
      discernment, practical wisdom and a knowledge base that justifies reasoning and
      actions that support patient and family decision making. Nurses' moral knowledge
      develops through experiential learning, didactic learning, and deliberation of
      ethical principles that merge with moral intuition, ethical codes, and moral
      theories. Only when a nurse becomes skilled and confident in gathering empiric
      and ethical knowledge can he or she fully act as a moral agent in assisting
      families faced with making highly emotional decisions regarding the provision,
      withholding, or withdrawal of artificial nutrition and hydration.

PMID- 19850188
TI  - Imbalanced diet vs. sedentary lifestyle: the burden of history.

PMID- 19850187
TI  - Nursing, religiosity, and end-of-life care: interconnections and implications.
AB  - The influence of religious beliefs and practices at the end of life is
      underinvestigated. Given nursing's advocacy role and the intimate and personal
      nature of the dimensions of religiosity and the end of life, exploring the
      multidimensional interplay of religiosity and end-of-life care is a significant
      aspect of the nurse-patient relationship and must be better understood. The
      question that must be faced is whether nurses' own belief systems impinge on or
      influence patient care, especially for patients who are at the end of life. When
      nurses understand their own beliefs and respect the religious practices and needs
      of patients and their families, it deepens the humanistic dimensions of the nurse
      patient relationship.

PMID- 19850189
TI  - Cosmetic dermatology. Preface.

PMID- 19850190
TI  - Cosmeceuticals: practical applications.
AB  - Cosmeceuticals are topically applied products that are more than merely cosmetic,
      yet are not true drugs that have undergone rigorous placebo controlled studies
      for safety and efficacy. There are many review articles that outline the
      theoretical biologic and clinical actions of these cosmeceuticals and their
      various ingredients. This article reviews how to incorporate various
      cosmeceuticals into the treatment regime of patients, depending on the diagnosis
      and therapies chosen. The practical application of when, why, and on whom to use
      different products will enable dermatologists to improve the methodology of
      product selection and, ultimately, improve patient's clinical results.

PMID- 19850191
TI  - Botulinum toxin in facial rejuvenation: an update.
AB  - Since its initial approval by the US Food and Drug Administration (FDA) 20 years
      ago for the treatment of strabismus, hemifacial spasm, and blepharospasm in
      adults, botulinum toxin (BTX) has become one of the most frequently requested
      products in cosmetic rejuvenation around the world. After years of clinical
      success and consistent safety in the upper face, the use of BTX has expanded and
      evolved to include increasingly complicated indications. In the hands of adept
      injectors, the focus has shifted from the treatment of individual dynamic
      rhytides to shaping, contouring, and sculpting, alone or in combination with
      other cosmetic procedures, to enhance the aesthetic appearance of the face.
      Although recent reports have questioned the safety of BTX, 25 years of
      therapeutic and over 20 years of cosmetic use has demonstrated an impressive
      record of safety and efficacy when used appropriately by experienced injectors.

PMID- 19850192
TI  - Dermal fillers and combinations of fillers for facial rejuvenation.
AB  - Until recently, the use of dermal fillers was limited in the United States by the
      small number of products approved by the Food and Drug Administration. The
      products now approved for use in the United States have opened up the range of
      possibilities for combinations of products that are synergistic in their effects.
      Combinations of products may be discussed in temporal or anatomic relationships.
      Temporal combinations refer to the use of different fillers at different times,
      whereas anatomic combinations refer to the use of different fillers in different
      parts of the face. Before discussing how the various fillers may be used in
      combination, it is worthwhile to consider their use in isolation. Soft-tissue
      augmentation products under consideration in the present article include the
      hyaluronic acids (HA), poly L lactic acid (PLLA), calcium hydroxylapatite (CAHA),
      porcine collagen, and silicone.

PMID- 19850193
TI  - Semipermanent and permanent injectable fillers.
AB  - Today, an impressive array of injectable dermal fillers for facial soft-tissue
      augmentation is available in the United States. These agents, most of which were
      introduced in the last half decade, represent a variety of semipermanent and
      permanent fillers across several categories. Physicians can choose between
      semipermanent fillers, such as hyaluronic acid derivatives (HA), calcium
      hydroxylapatite (CaHA), and poly-L-lactic acid (PLA), and longer-lasting, so
      called "permanent fillers," such as polymethyl methacrylate microspheres (PMMA),
      highly purified forms of liquid silicone, and hydrogel polymers.

PMID- 19850194
TI  - Photorejuvenation.
AB  - Aging is an ongoing process. The ultraviolet rays of the sun cause cutaneous
      changes such as damage to collagen, solar elastosis, telangiectasias, lentigines,
      and rhytid formation; the collective description of these negative effects is
      photodamage. Photorejuvenation is the process of using laser and light sources
      for returning skin to a more youthful appearance. This article explores the
      technology, clinical applications, side effects, and future directions of
      photorejuvenation with vascular lasers, pigmented lasers, and intense pulsed
      light sources.

PMID- 19850195
TI  - Multimodal treatment of acne, acne scars and pigmentation.
AB  - Acne is a common skin disease that affects nearly 80% of adolescents and young
      adults aged 11 to 30 years. Lesions appear primarily on the face, back, chest,
      and other areas with a high concentration of pilosebaceous glands. The
      development of inflammatory lesions often drives acne patients to seek treatment.
      If a lesion becomes severely inflamed it may leave a scar. Severe scarring caused
      by acne is associated with substantial physical and psychological distress,
      particularly in adolescents. This article reviews the causes of acne, the
      treatment options, and grading scales.

PMID- 19850196
TI  - Nonablative fractional laser resurfacing.
AB  - Nonablative fractional resurfacing (NFR) uses a mode of delivery with
      preservation of the stratum corneum, a true resurfacing with epidermal extrusion,
      and creation of microscopic thermal zones of injury that ultimately lead to
      neocollagenesis. This article discussed the science, clinical indications,
      patient selection and preparation, posttreatment care, and complications of NFR.
      It concludes that the most impressive clinical results are seen with acne scars,
      surgical and traumatic scars, and mild to moderate facial and nonfacial
      dyschromia or photoaging. Modest results can be seen with therapy-resistant
      melasma and certain types of rhytides. Future approaches include synergistic
      treatments with radiofrequency devices and the development of novel wavelengths
      to enhance the efficacy of NFR while preserving safety.

PMID- 19850197
TI  - Ablative and fractional ablative lasers.
AB  - The field of nonsurgical laser resurfacing for aesthetic enhancement continues to
      improve with new research and technological advances. Since its beginnings in the
      1980s, the laser-resurfacing industry has produced a multitude of devices
      employing ablative, nonablative, and fractional ablative technologies. The three
      approaches largely differ in their method of thermal damage, weighing degrees of
      efficacy, downtime, and side effect profiles against each other. Nonablative
      technologies generate some interest, although only for those patient populations
      seeking mild improvements. Fractional technologies, however, have gained dramatic
      ground on fully ablative resurfacing. Fractional laser resurfacing, while
      exhibiting results that fall just short of the ideal outcomes of fully ablative
      treatments, is an increasingly attractive alternative because of its far more
      favorable side effect profile, reduced recovery time, and significant clinical
      outcome.

PMID- 19850198
TI  - Tissue tightening technologies.
AB  - Results with current skin-tightening technologies are mild to moderate and are
      not intended to replace surgical procedures. Many patients will choose more
      subtle tightening to avoid the risks and downtime associated with surgery. Newer
      treatment protocols have improved treatment predictability and the extent of
      efficacy, and novel technologies with the potential for even greater results are
      currently in development. Overall patients' satisfaction can be increased by
      combining skin tightening with complementary, noninvasive skin treatments, such
      as botulinum toxin and soft-tissue fillers.

PMID- 19850199
TI  - Cosmetic dermatology: legal issues.
AB  - Laser and light-based procedures, fillers, toxins and various peels have
      revolutionized the field of cosmetic dermatology. With an increasing number of
      physicians and nonphysicians performing these procedures, and with the
      availability of a seemingly unlimited array of cosmetic dermatology procedures,
      the potential for problems and their legal consequences continue to increase.
      This article will discuss the concept of negligence and the potential for medical
      malpractice, including the associated problems that may arise when these
      procedures are performed by physician extenders. The impact of the physician and
      physician extender relationship, and the legal issues that arise, are also
      discussed. The article concludes with the legal and ethical issues associated
      with the promotion of cosmeceutical agents in the field of cosmetic dermatology.

PMID- 19850200
TI  - Complications and their management in cosmetic dermatology.
AB  - Current aesthetic dermatology rejuvenation options offer minimally invasive, more
      affordable alternatives to traditional cosmetic surgery. Chemical peels and laser
      resurfacing can significantly improve the appearance of the skin and stimulate
      neocollagenesis; botulinum toxin reduces the appearance of dynamic facial lines;
      and dermal fillers can restore facial fullness. These nonsurgical procedures also
      carry potential risks. This article reviews potential complications of these
      procedures and best practices for clinical management to improve outcomes.

PMID- 19850201
TI  - Emerging technologies in aesthetic medicine.
AB  - Recent advances in technology have drastically improved aesthetic treatment for
      skin. Of particular interest is the emergence of laser- and lightbased
      technologies, which have offered great promise among skin-rejuvenation therapies.
      New laser resurfacing techniques for skin rejuvenation offer significant
      advantages over conventional ablative lasers, such as the CO(2) and erbiumYAG
      laser systems. Nonablative and fractional lasers, although not as efficacious as
      ablative therapies, are associated with significantly diminished complication
      rates and shortened recovery times. Novel devices combining ablative and
      fractional technologies have also surfaced, demonstrating noteworthy results. In
      this review, the authors will discuss the implications of current developments in
      research and technology for skin rejuvenation. Furthermore, the authors will
      address emerging therapies for acne vulgaris, lipolysis, and cellulite.

PMID- 19850202
TI  - Skin type classification systems old and new.
AB  - The history of classifying skin types is rather new and there has been
      considerable progress made with continuing awareness. The Fitzpatrick Skin
      Phototype Classification remains the gold standard. It is simple and user
      friendly, however this system fails to accurately predict skin reactions. The
      Roberts Skin Type Classification System is a tool to predict the skin response to
      injury and insult from cosmetic procedures and identify the propensity of
      sequelae from inflammatory skin disorders. It can be a predictor of an impending
      complication, such as hyperpigmentation and scarring, which can then be avoided.
      In addition, it includes the skin phototype and photoage. In evaluating patients'
      skin and developing a cosmetic plan, the four indices outlined in this article,
      hyper/hypopigmentation risk, scarring risk, skin phototype, and photoage, are
      crucial to identify for optimal outcomes.

PMID- 19850203
TI  - False-positive stress tests... or false-negative rest angiograms?

PMID- 19850204
TI  - The adrenergic-fatty acid load in heart failure.
AB  - The hypothesis proposed is that heart failure (HF) is associated with a reactive
      hyperadrenergic state that increases circulating plasma free fatty acids (FFAs),
      which leads to impaired glucose metabolism and insulin resistance. We propose
      that increased FFA-induced mitochondrial uncoupling and substantial oxygen
      wastage is closely associated with the generation of reactive oxygen species,
      inflammatory markers, and the development of insulin resistance. The therapeutic
      aims of metabolic therapy are as follows: 1) to decrease hyperadrenergic drive;
      2) to inhibit lipotoxicity and glucotoxicity; and 3) to increase glucose uptake
      by muscle. These aims are achieved, respectively, by the following: 1) the use of
      beta-adrenergic blockade and all measures that relieve the mechanical load on the
      heart; 2) the use of drugs that inhibit fatty acid oxidation (trimetazidine,
      perhexiline), although without clinical evidence that the heart is their major
      site of action in HF; and 3) increase of the transport of glucose into the cells
      by exercise and metformin. Of these measures, only data concerning the reduction
      of mortality as the result of exercise are available. Of all the other measures,
      there are substantial positive data on the use of trimetazidine that demonstrate
      metabolic and clinical benefit with almost no side effects, but data from a large
      outcome trial are lacking. Our data suggest a major extracardiac site of
      trimetazidine action. Ranolazine, which inhibits the late sodium inward current,
      requires testing in human HF. Insulin to reduce hyperglycemia and FFAs is
      untested in HF, with incretins such as glucagon-like peptide-1 on the horizon.
      Other future therapies may include malonyl-coenzyme A regulators to inhibit fatty
      acid oxidation, fish oil omega-3, and activators of protein kinase C-epsilon.

PMID- 19850205
TI  - Ventricular assist devices the challenges of outpatient management.
AB  - The need for mechanical assistance of the failing heart, whether acute after a
      myocardial infarction or permanent in patients with end-stage heart failure, has
      increased with improvements in medical therapy and a growing aged population.
      Over the past few decades, much progress has been made in the development and
      refinement of ventricular assist devices (VADs), medical devices capable of
      maintaining circulatory output of the diseased ventricle. Initially designed as a
      temporary support to allow ventricular recovery or as a bridge for patients to
      cardiac transplantation, these devices are now being used as a permanent form of
      "destination" therapy. Improvements in technological design, durability, and
      medical management have allowed individuals with VADs to be managed in their
      communities. Although these devices provide excellent hemodynamic support and
      enhance patient functional status, discharged individuals face many unique
      challenges. In this article, we discuss 1) the spectrum of VADs for outpatient
      therapy, including their basic physiology and hemodynamics; 2) the
      multidisciplinary approach required to care for a patient with such a device in
      the community; 3) routine general cardiac issues that are encountered; 4)
      associated long-term device and nondevice-related complications; and 5) the
      reported overall improvements in quality of life.

PMID- 19850206
TI  - Micronutrient deficiencies an unmet need in heart failure.
AB  - Heart failure (HF) is a common, disabling, and costly disease. Despite major
      advances in medical therapy, morbidity and mortality remain high, in part because
      current pharmacological regimens may not fully address some unique requirements
      of the heart for energy. The heart requires a continuous supply of energy
      providing substrates and amino acids in order to maintain its function. In HF,
      defects in substrate metabolism and cardiac energy and substrate utilization may
      contribute to contractile dysfunction. HF is often accompanied by a deficiency in
      key micronutrients required for unimpeded energy transfer. Correcting these
      deficits has been proposed as a method to limit or even reverse the progressive
      myocyte dysfunction and/or necrosis in HF. This review summarizes the existing HF
      literature with respect to supplementation trials of key micronutrients involved
      in cardiac metabolism: coenzyme Q10, l-carnitine, thiamine, and amino acids,
      including taurine. Studies using a broader approach to supplementation are also
      considered. Although some of the results are promising, none are conclusive.
      There is a need for a prospective trial to examine the effects of micronutrient
      supplementation on morbidity and mortality in patients with HF.

PMID- 19850207
TI  - Natural history of markers of collagen turnover in patients with early diastolic
      dysfunction and impact of eplerenone.
AB  - OBJECTIVES: This study was designed to evaluate the impact of eplerenone on
      collagen turnover in preserved systolic function heart failure (HFPSF).
      BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature
      of HFPSF with diastolic dysfunction, the natural history of markers of collagen
      turnover and the impact of selective aldosterone antagonism on this natural
      history remains unknown. METHODS: We evaluated 44 patients with HFPSF, randomly
      assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months,
      increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover
      and inflammation were analyzed at baseline and at 6 and 12 months and included
      pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase
      type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler
      echocardiographic assessment of diastolic filling indexes and tissue Doppler
      analyses were also obtained. RESULTS: The mean age of the patients was 80 +/- 7.8
      years; 46% were male; 64% were receiving an angiotensin-converting enzyme
      inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta
      blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix
      metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha
      increased with time in the control group. Eplerenone treatment had no significant
      impact on any biomarker at 6 months but attenuated the increase in pro-collagen
      type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was
      associated with modest effects on diastolic function without any impact on
      clinical variables or brain natriuretic peptide. CONCLUSIONS: This study
      demonstrates progressive increases in markers of collagen turnover and
      inflammation in HFPSF with diastolic dysfunction. Despite high background
      utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy
      prevents a progressive increase in pro-collagen type-III aminoterminal peptide
      and may have a role in management of this disease. (The Effect of Eplerenone and
      Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure;
      NCT00505336).

PMID- 19850208
TI  - A meta-analysis of remote monitoring of heart failure patients.
AB  - OBJECTIVES: The purpose of this study was to assess the effect of remote patient
      monitoring (RPM) on the outcome of chronic heart failure (HF) patients.
      BACKGROUND: RPM via regularly scheduled structured telephone contact between
      patients and health care providers or electronic transfer of physiological data
      using remote access technology via remote external, wearable, or implantable
      electronic devices is a growing modality to manage patients with chronic HF.
      METHODS: After a review of the literature published between January 2000 and
      October 2008 on a multidisciplinary heart failure approach by either usual care
      (in-person visit) or RPM, 96 full-text articles were retrieved: 20 articles
      reporting randomized controlled trials (RCTs) and 12 reporting cohort studies
      qualified for a meta-analysis. RESULTS: Respectively, 6,258 patients and 2,354
      patients were included in RCTs and cohort studies. Median follow-up duration was
      6 months for RCTs and 12 months for cohort studies. Both RCTs and cohort studies
      showed that RPM was associated with a significantly lower number of deaths (RCTs:
      relative risk [RR]: 0.83, 95% confidence interval [CI]: 0.73 to 0.95, p = 0.006;
      cohort studies: RR: 0.53, 95% CI: 0.29 to 0.96, p < 0.001) and hospitalizations
      (RCTs: RR: 0.93, 95% CI: 0.87 to 0.99, p = 0.030; cohort studies: RR: 0.52, 95%
      CI: 0.28 to 0.96, p < 0.001). The decrease in events was greater in cohort
      studies than in RCTs. CONCLUSIONS: RPM confers a significant protective clinical
      effect in patients with chronic HF compared with usual care.

PMID- 19850210
TI  - Hospitalizations in patients with heart failure: who and why.

PMID- 19850209
TI  - Hospitalizations after heart failure diagnosis a community perspective.
AB  - OBJECTIVES: The purpose of this study was to determine the lifetime burden and
      risk factors for hospitalization after heart failure (HF) diagnosis in the
      community. BACKGROUND: Hospitalizations in patients with HF represent a major
      public health problem; however, the cumulative burden of hospitalizations after
      HF diagnosis is unknown, and no consistent risk factors for hospitalization have
      been identified. METHODS: We validated a random sample of all incident HF cases
      in Olmsted County, Minnesota, from 1987 to 2006 and evaluated all
      hospitalizations after HF diagnosis through 2007. International Classification of
      Diseases-9th Revision codes were used to determine the primary reason for
      hospitalization. To account for repeated events, Andersen-Gill models were used
      to determine the predictors of hospitalization after HF diagnosis. Patients were
      censored at death or last follow-up. RESULTS: Among 1,077 HF patients (mean age
      76.8 years, 582 [54.0%] female), 4,359 hospitalizations occurred over a mean
      follow-up of 4.7 years. Hospitalizations were common after HF diagnosis, with 895
      (83.1%) patients hospitalized at least once, and 721 (66.9%), 577 (53.6%), and
      459 (42.6%) hospitalized > or =2, > or =3, and > or =4 times, respectively. The
      reason for hospitalization was HF in 713 (16.5%) hospitalizations and other
      cardiovascular in 936 (21.6%), whereas over one-half (n = 2,679, 61.9%) were
      noncardiovascular. Male sex, diabetes mellitus, chronic obstructive pulmonary
      disease, anemia, and creatinine clearance <30 ml/min were independent predictors
      of hospitalization (p < 0.05 for each). CONCLUSIONS: Multiple hospitalizations
      are common after HF diagnosis, though less than one-half are due to
      cardiovascular causes. Comorbid conditions are strongly associated with
      hospitalizations, and this information could be used to define effective
      interventions to prevent hospitalizations in HF patients.

PMID- 19850212
TI  - Stressful sleeping.

PMID- 19850211
TI  - Hypoxia, not the frequency of sleep apnea, induces acute hemodynamic stress in
      patients with chronic heart failure.
AB  - OBJECTIVES: This study was conducted to evaluate whether brain (B-type)
      natriuretic peptide (BNP) changes during sleep are associated with the frequency
      and severity of apneic/hypopneic episodes, intermittent arousals, and hypoxia.
      BACKGROUND: Sleep apnea is strongly associated with heart failure (HF) and could
      conceivably worsen HF through increased sympathetic activity, hemodynamic stress,
      hypoxemia, and oxidative stress. If apneic activity does cause acute stress in
      HF, it should increase BNP. METHODS: Sixty-four HF patients with New York Heart
      Association functional class II and III HF and ejection fraction <40% underwent a
      baseline sleep study. Five patients with no sleep apnea and 12 with severe sleep
      apnea underwent repeat sleep studies, during which blood was collected every 20
      min for the measurement of BNP. Patients with severe sleep apnea also underwent a
      third sleep study with frequent BNP measurements while they were administered
      oxygen. This provided 643 observations with which to relate apnea to BNP. The
      association of log BNP with each of 6 markers of apnea severity was evaluated
      with repeated measures regression models. RESULTS: There was no relationship
      between BNP and the number of apneic/hypopneic episodes or the number of
      arousals. However, the burden of hypoxemia (the time spent with oxygen saturation
      <90%) significantly predicted BNP concentrations; each 10% increase in duration
      of hypoxemia increased BNP by 9.6% (95% confidence interval: 1.5% to 17.7%, p =
      0.02). CONCLUSIONS: Hypoxemia appears to be an important factor that underlies
      the impact of sleep abnormalities on hemodynamic stress in patients with HF.
      Prevention of hypoxia might be especially important for these patients.

PMID- 19850213
TI  - Profiles of serial changes in cardiac troponin T concentrations and outcome in
      ambulatory patients with chronic heart failure.
AB  - OBJECTIVES: The purpose of this study was to determine whether different profiles
      of cardiac troponin T (cTnT) values assessed over time would yield incremental
      prognostic information on clinically stable outpatients with heart failure (HF).
      BACKGROUND: cTnT levels were used to estimate prognosis in HF; however, most
      studies evaluated hospitalized patients using single measurements. METHODS: A
      cohort of 172 New York Heart Association functional class III to IV outpatients
      was prospectively studied with serial cTnT measurements collected every 3 months
      over a 2-year period. The primary end point was death or cardiac transplantation,
      and secondary end points included HF hospitalization. RESULTS: Of the 172
      patients, 22 (13%) died or underwent transplantation during the first year.
      Therefore, 150 patients were included in the second-year analysis of 3 pre
      determined groups: 1) no serial cTnT elevations (defined as <0.01 ng/ml); 2) 1 or
      more, but not all cTnT values elevated > or =0.01 ng/ml; and 3) all cTnT values
      elevated during the first year. During the second year, 30 events occurred: 53
      patients had persistently normal cTnT levels (<0.01 ng/ml) with 6 primary events
      (11%); 57 patients had 1 or more but not all cTnT levels elevated with 11 events
      (19%); 40 patients demonstrated persistently elevated cTnT levels with 13 (33%)
      primary events (odds ratio: 3.77; 95% confidence interval: 1.28 to 11.07, p =
      0.02). CONCLUSIONS: Elevations in cTnT, even using a low threshold of 0.01 ng/ml,
      detected during routine clinical follow-up of ambulatory patients with HF, are
      highly associated with an increased risk of events, particularly with frequent or
      persistent cTnT elevations of > or =0.01 ng/ml. Therefore, the ability to monitor
      clinical change through serial cTnT measurements may add to risk assessment in
      the ambulatory HF population.

PMID- 19850214
TI  - Implantation of the melody transcatheter pulmonary valve in patients with a
      dysfunctional right ventricular outflow tract conduit early results from the u.s.
      Clinical trial.
AB  - OBJECTIVES: This study was designed to evaluate the safety, procedural success,
      and short-term effectiveness of the Melody transcatheter pulmonary valve
      (Medtronic, Inc., Minneapolis, Minnesota) in patients with dysfunctional right
      ventricular outflow tract conduits. BACKGROUND: Conduit dysfunction has recently
      been treated with transcatheter pulmonary valve placement. There have been no
      prospective, multicenter trials evaluating this technology. METHODS: Standardized
      entry criteria, implantation, and follow-up protocols were used. Nonimplanting
      core laboratories were used to evaluate results. RESULTS: Between January 2007
      and September 2007, 34 patients underwent catheterization for intended Melody
      valve implantation at 3 centers. Mean age was 19.4 +/- 7.7 years. Initial conduit
      Doppler mean gradient was 28.8 +/- 10.1 mm Hg, and 94% of patients had moderate
      or severe pulmonary regurgitation (PR). Implantation was successful in 29 of 30
      attempts and not attempted in 4 patients. Procedural complications included
      conduit rupture requiring urgent surgery and device removal (n = 1), wide-complex
      tachycardia (n = 1), and distal pulmonary artery guidewire perforation (n = 1).
      Peak systolic conduit gradient fell acutely from 37.2 +/- 16.3 mm Hg to 17.3 +/-
      7.3 mm Hg, and no patient had more than mild PR. There were no deaths or further
      device explants. At 6-month follow-up, conduit Doppler mean gradient was 22.4 +/-
      8.1 mm Hg, and PR fraction by magnetic resonance imaging was significantly
      improved (3.3 +/- 3.6% vs. 27.6 +/- 13.3%, p < 0.0001). Stent fracture occurred
      in 8 of 29 implants; 3 of these were treated with a second Melody valve for
      recurrent stenosis later in follow-up. CONCLUSIONS: Implantation of the Melody
      valve for right ventricular outflow tract conduit dysfunction can be performed by
      experienced operators at multiple centers, appears safe, and has encouraging
      acute and short-term outcomes.

PMID- 19850215
TI  - High central pulse pressure is independently associated with adverse
      cardiovascular outcome the strong heart study.
AB  - OBJECTIVES: This study was designed to facilitate clinical use of central pulse
      pressure (PP). We sought to determine a value that might predict adverse outcome
      and thereby provide a target for assessment of intervention strategies.
      BACKGROUND: We previously documented that central PP more strongly relates to
      carotid hypertrophy and extent of atherosclerosis and, more importantly, better
      predicts incident cardiovascular disease (CVD) than brachial PP. METHODS: Radial
      applanation tonometry was performed in the third Strong Heart Study examination
      to determine central blood pressure. Cox regression analyses were performed using
      pre-specified covariates and quartiles of central and brachial PP. RESULTS: Among
      2,405 participants without prevalent CVD, 344 suffered CVD events during 5.6 +/-
      1.7 years. Quartiles of central PP (p < 0.001) predicted outcome more strongly
      than quartiles of brachial PP (p = 0.052). With adjustment for covariates, only
      the event rate in the fourth quartile of central PP (> or =50 mm Hg) was
      significantly higher than that in the first quartile (hazard ratio [HR]: 1.69,
      95% confidence interval [CI]: 1.20 to 2.39, p = 0.003). Central PP > or =50 mm Hg
      was related to outcome in both men (HR: 2.06, 95% CI: 1.39 to 3.04, p < 0.001)
      and women (HR: 2.03, 95% CI: 1.55 to 2.65, p < 0.001); in participants with (HR:
      1.84, 95% CI: 1.41 to 2.39, p < 0.001) and without diabetes (HR: 1.91, 95% CI:
      1.29 to 2.83, p = 0.001); and in individuals younger (HR: 2.51, 95% CI: 1.59 to
      3.95, p < 0.001) and older (HR: 1.53, 95% CI: 1.19 to 1.97, p = 0.001) than the
      age of 60 years. CONCLUSIONS: Central PP > or =50 mm Hg predicts adverse CVD
      outcome and may serve as a target in intervention strategies if confirmed in
      other populations and in prospective studies.

PMID- 19850216
TI  - Comparison of gene delivery techniques for therapeutic angiogenesis ultrasound
      mediated destruction of carrier microbubbles versus direct intramuscular
      injection.
AB  - OBJECTIVES: This study was designed to compare the efficacy of angiogenic gene
      delivery by ultrasound-mediated (UM) destruction of intravenous carrier
      microbubbles to direct intramuscular (IM) injections. BACKGROUND: Current trials
      of gene therapy for angiogenesis remain limited by suboptimal, invasive delivery
      techniques. METHODS: Hind-limb ischemia was produced by iliac artery ligation in
      99 rats. In 32 rats, UM delivery of green fluorescent protein (GFP)/vascular
      endothelial growth factor-165 (VEGF(165)) plasmid deoxyribonucleic acid was
      performed. Thirty-five animals received IM injections of VEGF(165)/GFP plasmid.
      Remaining rats received no treatment. Before delivery (day 14 after ligation) and
      at days 17, 21, and 28 and week 8 after ligation, microvascular blood volume and
      microvascular blood flow to the proximal hind limbs were assessed by contrast
      enhanced ultrasound (n = 8 per group). Total transfection was assessed by reverse
      transcriptase-polymerase chain reaction, and localization of transfection was
      determined by immunohistochemistry. RESULTS: By day 28, both IM and UM delivery
      of VEGF(165) produced significant increases in microvascular blood volume and
      microvascular blood flow. Whereas increases in microvascular blood volume were
      similar between treatment groups, microvascular blood flow was greater (p <
      0.005) in UM-treated animals as compared with IM-treated animals, persisting to
      week 8. The VEGF(165)/GFP messenger ribonucleic acid expression was greater (p <
      0.05) for IM-treated animals. A strong GFP signal was detected for both groups
      and was localized to focal perivascular regions and myocytes around injection
      sites for IM and to the vascular endothelium of arterioles/capillaries in a wider
      distribution for UM delivery. CONCLUSIONS: Despite lower transfection levels, UM
      delivery of VEGF(165) is as effective as IM injections. The UM delivery results
      in directed vascular transfection over a wider distribution, which may account
      for the more efficient angiogenesis.

PMID- 19850217
TI  - Arteriovenous malformation culprit or innocent bystander?

PMID- 19850218
TI  - ACC 2009 Advocacy Position Statement: Principles for comparative effectiveness
      research.

PMID- 19850219
TI  - HIV vaccine trials and tribulations.

PMID- 19850220
TI  - Vaccine immunogenicity in injecting drug users.

PMID- 19850221
TI  - Controlling hepatitis C with immunotherapy.

PMID- 19850222
TI  - Obama's research-funding stimulus.

PMID- 19850223
TI  - Has routine immunisation in Africa become endangered?

PMID- 19850224
TI  - A well-disguised blessing.

PMID- 19850225
TI  - Male circumcision and risk of HIV infection in women: a systematic review and
      meta-analysis.
AB  - Male circumcision provides long-term indirect protection to women by reducing the
      risk of heterosexual men becoming infected with HIV. In this Review, we summarise
      the evidence for a direct effect of male circumcision on the risk of women
      becoming infected with HIV. We identified 19 epidemiological analyses, from 11
      study populations, of the association of male circumcision and HIV risk in women.
      A random-effects meta-analysis of data from the one randomised controlled trial
      and six longitudinal analyses showed little evidence that male circumcision
      directly reduces risk of HIV in women (summary relative risk 0.80, 95% CI 0.53
      1.36). Definitive data would come from a further randomised controlled trial of
      circumcision among men infected with HIV in serodiscordant heterosexual
      relationships, but this would involve enrolling about 10 000 couples and is
      likely to be logistically unfeasible. As circumcision services for HIV prevention
      are scaled-up in high HIV prevalence settings, rapid integration with existing
      prevention strategies would maximise benefits for both men and women. Rigorous
      monitoring is essential to ensure that any adverse effects on women are detected
      and minimised.

PMID- 19850226
TI  - Progress towards a dengue vaccine.
AB  - The spread of dengue virus throughout the tropics represents a major, rapidly
      growing public health problem with an estimated 2.5 billion people at risk of
      dengue fever and the life-threatening disease, severe dengue. A safe and
      effective vaccine for dengue is urgently needed. The pathogenesis of severe
      dengue results from a complex interaction between the virus, the host, and, at
      least in part, immune-mediated mechanisms. Vaccine development has been slowed by
      fears that immunisation might predispose individuals to the severe form of dengue
      infection. A pipeline of candidate vaccines now exists, including live
      attenuated, inactivated, chimeric, DNA, and viral-vector vaccines, some of which
      are at the stage of clinical testing. In this Review, we present what is
      understood about dengue pathogenesis and its implications for vaccine design, the
      progress that is being made in the development of a vaccine, and the future
      challenges.

PMID- 19850227
TI  - Genetic deficiencies of innate immune signalling in human infectious disease.
AB  - The type-1 cytokine (interleukin 12, interleukin 23, interferon gamma,
      interleukin 17) signalling pathway is triggered during infection by activation of
      phagocyte-expressed pattern-recognition receptors that recognise specific
      pathogen-associated molecular patterns. Triggering of this pathway results, among
      other things, in activation of microbicidal mechanisms in phagocytic cells.
      Individuals with a deficiency in one of the proteins in the pathway are unusually
      susceptible to otherwise poorly pathogenic, mostly environmental, mycobacteria
      and salmonellae. Individuals with deficiencies in other innate immune signalling
      proteins show unusual susceptibility to pathogens other than mycobacteria or
      salmonellae. We discuss recent insights into key molecules involved in type-1
      cytokine signalling pathways and provide an update on the molecular genetic
      defects underlying mendelian susceptibility to mycobacterial disease. We also
      discuss deficiencies in the innate immune signalling proteins that lead to
      susceptibility to other pathogens. Knowledge of innate immune signalling has
      allowed the identification of defects in such patients. However, some patients
      have enhanced susceptibility to pathogens even though no mutations have been
      found in the candidate genes identified thus far. Whereas a few patients might
      have autoantibodies against type-1 cytokines, others might harbour mutations in
      new genes and pathways that still need to be identified.

PMID- 19850228
TI  - Pathogenetic mechanisms of the intracellular parasite Mycobacterium ulcerans
      leading to Buruli ulcer.
AB  - The necrotising skin infection Buruli ulcer is at present the third most common
      human mycobacteriosis worldwide, after tuberculosis and leprosy. Buruli ulcer is
      an emergent disease that is predominantly found in humid tropical regions. There
      is no vaccine against Buruli ulcer and its treatment is difficult. In addition to
      the huge social effect, Buruli ulcer is of great scientific interest because of
      the unique characteristics of its causative organism, Mycobacterium ulcerans.
      This pathogen is genetically very close to the typical intracellular parasites
      Mycobacterium marinum and Mycobacterium tuberculosis. We review data supporting
      the interpretation that M ulcerans has the essential hallmarks of an
      intracellular parasite, producing infections associated with immunologically
      relevant inflammatory responses, cell-mediated immunity, and delayed-type
      hypersensitivity. This interpretation judges that whereas M ulcerans behaves like
      the other pathogenic mycobacteria, it represents an extreme in the biodiversity
      of this family of pathogens because of its higher cytotoxicity due to the
      secretion of the exotoxin mycolactone. The acceptance of the interpretation that
      Buruli ulcer is caused by an intracellular parasite has relevant prophylactic and
      therapeutic implications, rather than representing the mere attribution of a
      label with academic interest, because it prompts the development of vaccines that
      boost cell-mediated immunity and the use of chemotherapeutic protocols that
      include intracellularly active antibiotics.

PMID- 19850229
TI  - Operational research in low-income countries: what, why, and how?
AB  - Operational research is increasingly being discussed at institutional meetings,
      donor forums, and scientific conferences, but limited published information
      exists on its role from a disease-control and programme perspective. We suggest a
      definition of operational research, clarify its relevance to infectious-disease
      control programmes, and describe some of the enabling factors and challenges for
      its integration into programme settings. Particularly in areas where the disease
      burden is high and resources and time are limited, investment in operational
      research and promotion of a culture of inquiry are needed so that health care can
      become more efficient. Thus, research capacity needs to be developed, specific
      resources allocated, and different stakeholders (academic institutions, national
      programme managers, and non-governmental organisations) brought together in
      promoting operational research.

PMID- 19850230
TI  - Bone marrow involvement in Q fever--detection by fluorine-18-labelled
      fluorodeoxyglucose PET.

PMID- 19850231
TI  - Pseudomorbidity in iliac crest bone graft harvesting: the rise of rhBMP-2 in
      short-segment posterior lumbar fusion.

PMID- 19850232
TI  - A novel alternative for removal of the AxiaLif (TranS1) in the setting of
      pseudarthrosis of L5-S1.
AB  - BACKGROUND: Minimally invasive spine surgery continues to be a growing trend for
      orthopedic and neurosurgical spinal interventions. Technological advances have
      allowed surgeons to perform L5-S1 fusions via posterolateral or anterior
      approaches through less invasive techniques. The development of the AxiaLIF
      system (TranS1, Inc., Wilmington, NC) is predicated on the application of
      minimally invasive techniques to attain fusion at L5-S1 and L4-S1 levels with a
      novel corridor of approach, described as the presacral "safe zone." PURPOSE: The
      authors describe an alternative approach for removing a L5-S1 transsacral implant
      that was placed through a percutaneous paracoccygeal approach using the presacral
      safe zone. The purpose of this technical note is to demonstrate that use of the
      previous percutaneous presacral tract, as recommended by the manufacturer, is not
      mandatory. In cases of anterior pseudarthrosis following this device, a
      paramedian retroperitoneal approach to L5-S1 not only allows for adequate
      visualization for revision but also provides adequate and safe caudal exposure
      over the sacral promontory to remove the implant through its previous osseous
      path. STUDY DESIGN/SETTING: This technical note highlights the concerns for
      revision of the AxiaLif (TranS1) screw through the presacral scarred tract.
      METHODS: The AxiaLif (TranS1), used in this case is an alternative method to
      anterior, posterior, or transforaminal lumbar interbody fusion. Removal of this
      implant for pseudarthrosis was performed through a paramedian retroperitoneal
      approach with caudal extension. After anterior discectomy, the AxiaLif screw was
      removed via manipulation through the disc space and delivered through the sacrum.
      This was followed by complete discectomy and bone grafting of the voids left in
      the L5 and sacral vertebral bodies. Standard anterior lumbar interbody
      reconstruction was then performed using a polyetheretherketone implant followed
      by revision of the pedicle screw construct posteriorly. RESULTS: Preoperative
      symptoms were resolved in the immediate postoperative period secondary to the
      immediate stability afforded by the revision of the loose implants. Fusion was
      achieved within 6 months and confirmed with fine-cut computed tomography images.
      CONCLUSION: This novel technique of avoiding a scarred down presacral corridor in
      the hands of surgeons unfamiliar with the technique allows for safe removal of
      the AxiaLif (TranS1) implant coupled with revision to anterior lumbar interbody
      fusion through the same incision.

PMID- 19850233
TI  - On confounders: known and unknown.

PMID- 19850234
TI  - Solutions without problems.

PMID- 19850235
TI  - The genomic era: "It's just the way I am" gives way to "look at what I might
      become!".

PMID- 19850236
TI  - A brave new beef: The US Food and Drug Administration's review of the safety of
      cloned animal products.
AB  - To meet its public mandate, the US Food and Drug Administration (FDA) collected
      studies on the potential health hazards of eating or drinking cloned food
      products. Based on an earlier National Academy of Sciences study that, on closer
      analysis, was not nearly as sanguine, the FDA's report found no evidence of a
      health risk from the public's ingestion of cloned food products. This article
      analyzes the risks the FDA considered, and concludes that there is a disconnect
      between the risks the FDA assessed in these studies and the risks that might
      arise from cloned food products. The FDA should consider instituting effective
      tracking mechanisms and other diagnostics that would permit scientists and the
      public to answer the question of health risks posed by cloned food products.

PMID- 19850237
TI  - Coronary artery disease: Are men and women created equal?
AB  - BACKGROUND: Ischemic heart disease in women is a difficult issue in
      cardiovascular medicine, mainly because of our lack of understanding of the early
      stage mechanisms and symptoms. A better and earlier understanding of the
      pathophysiology of coronary artery disease (CAD) in women will enable us to
      detect ischemic heart disease earlier and prevent adverse clinical outcomes.
      OBJECTIVES: The aims of this article were to describe the phenomenon of ischemic
      heart disease in women, increase awareness of the difference between men and
      women in relation to ischemic heart disease, improve our understanding of the
      mechanisms that cause this difference, and identify new approaches for better and
      earlier detection and treatment of CAD in women. METHODS: We conducted a search
      of the PubMed database for double-blind studies on the mechanistic pathways of
      CAD in women published in English within the past 10 years and epidemiologic
      studies published since 1970. Search terms included women and coronary artery
      disease and ischemic heart disease in women. RESULTS: The literature search
      revealed 30 peer-reviewed articles pertaining to this issue. The incidence of CAD
      was markedly lower in women <60 years of age than in older women. After 60 years
      of age, the rate of CAD increased and reached the rate seen among men by the 8th
      decade of life. The gender difference in atherosclerosis in the coronary tree was
      particularly large in patients <55 years of age and remained large at older ages.
      The gender difference in the coronary bed was strikingly larger than in other
      vascular beds. Intensive risk-factor modification had a similar effect on plaque
      progression in both men and women. Coronary endothelial dysfunction appeared to
      be related to cardiovascular morbidity and mortality in women as well as in men,
      and because endothelial dysfunction could be modified, it appeared that the
      prognosis could be improved by appropriate management. A strong association was
      found between body mass index (BMI) and metabolic status, but only the metabolic
      syndrome was associated with CAD. Physical activity was independently associated
      with fewer risk factors, less CAD, and fewer adverse events in women; however,
      obesity was not associated with these outcomes. CONCLUSIONS: Results of the
      identified studies suggest that reduction of risk factors is a common approach to
      fighting heart disease in both sexes. It appears that for women, weight and BMI
      are not as important as previously thought, but physical exercise and fitness are
      very important and can change risk factors and clinical outcomes more than any
      other known intervention. Data suggest that global inflammation may play an
      important role in women and may predict cardiovascular outcome in women much
      better than the traditional risk factors that have been used and proved for men.

PMID- 19850238
TI  - Women with atrial fibrillation: Greater risk, less attention.
AB  - BACKGROUND: In 1995, atrial fibrillation (AF) was estimated to affect 2.2 million
      people in the United States. After the age of 75 years (the median age for onset
      of AF), approximately 60% of people with AF are women. Women have a significantly
      higher risk of AF-related stroke than do men and are more likely to live with
      stroke-related disability and a significantly lower quality of life. OBJECTIVE:
      This article provides an overview of the contributing factors and clinical
      presentation of AF in women and offers a rational, safe, effective, and gender
      specific approach to therapy for women with AF. METHODS: Search engines,
      including PubMed and Google Scholar, were used to review the English-language
      literature addressing AF gender differences for the years 1989-2009. The search
      term atrial fibrillation was combined with multiple other terms, as well as with
      female, gender, sex, or women. Full-length manuscripts were reviewed. Original
      studies obtained were searched for additional relevant manuscripts using the
      cited references. RESULTS: Studies have shown that women are more likely than men
      to experience symptomatic attacks, a higher frequency of recurrences, and
      significantly higher heart rates during AF. Hormonal fluctuations during the
      menstrual cycle that affect QT intervals are an important consideration when
      selecting antiarrhythmic drugs for premenopausal women. Women are treated with
      statins less frequently than are men, possibly contributing to an increased
      incidence of AF in women. Women may have a higher incidence of AF because of the
      association with obesity. Some evidence suggests that women have a significantly
      higher risk of bleeding from anticoagulation. Reluctance among physicians and
      patients to use warfarin may be especially problematic in elderly women, who
      benefit most from it. Outcomes after catheter ablation for AF are similar between
      the sexes, yet women are referred later and less frequently. CONCLUSIONS: We
      favor emphasizing therapies to prevent AF and ensure safe arrhythmia management
      (ie, rate control and appropriate anticoagulation) once AF has been diagnosed.
      Gender differences should be kept in mind for women with AF to reduce risks and
      improve quality of life.

PMID- 19850239
TI  - Relationship between serum progesterone concentrations and cardiovascular
      disease, diabetes, and mortality in elderly Swedish men and women: An 8-year
      prospective study.
AB  - BACKGROUND: The use of synthetic progesterone-like substances in hormone
      replacement therapy and birth control pills has been associated with increases in
      cardiovascular morbidity and the prevalence of diabetes. OBJECTIVES: The primary
      aims of this study were to investigate whether physiologic concentrations of
      progesterone might also be associated with cardiovascular disease and diabetes,
      and to explore potential gender differences in these associations in elderly
      Swedish men and women. METHODS: This prospective, longitudinal study was
      performed in a Swedish population-based sample of opposite-sex twins aged between
      71 and 80 years who were not receiving sex hormone therapy. Serum concentrations
      of progesterone, estradiol, C-reactive protein (CRP), and urea were measured at
      baseline (1996) and at 8-year follow-up (2004), and serum concentrations of
      cystatin and insulin were measured only at follow-up. The outcomes of interest
      were cardiovascular morbidity (myocardial infarction, angina pectoris, peripheral
      arterial disease, stroke, congestive heart failure [CHF], cardiac arrhythmia,
      hypertension, and thromboembolism), diabetes, and mortality throughout the
      observation period. RESULTS: At baseline, the study sample included 230 men and
      195 women (mean [SD] age, 74.6 [2.6] years). At follow-up, 132 men and 145 women
      (mean age, 82.4 [2.5] years) met the inclusion criteria, of whom 128 men and 112
      women did so at both baseline and follow-up. Serum progesterone concentrations,
      which did not differ significantly from reported concentrations for the age
      group, were significantly associated with mortality across the observation period
      (P < 0.001). At follow-up, higher serum progesterone was significantly associated
      with the occurrence of CHF (P < 0.01); this association remained robust after
      adjustment for CRP, cystatin, and insulin levels. CONCLUSION: In these elderly
      Swedish men and women, increased physiologic concentrations of progesterone were
      found to be associated with an increased prevalence of CHF, independent of
      inflammatory factors, markers of renal function, and insulin metabolism.

PMID- 19850240
TI  - Early warning signs of an acute myocardial infarction and their influence on
      symptoms during the acute phase, with comparisons by gender.
AB  - BACKGROUND: Identifying early warning signs of an acute myocardial infarction
      (AMI) may aid in the early diagnosis of coronary artery disease. OBJECTIVES: This
      study was conducted to assess early warning signs (prodromal symptoms) of AMI,
      with comparisons made by gender. Another aim was to determine whether these early
      warning signs had any influence on the patients' acute symptoms of AMI. METHODS:
      This was a multicenter, cross-sectional study of Norwegian patients (aged <or=75
      years) hospitalized with their first AMI. A self-administered questionnaire was
      used to gather information on prodromal symptoms, defined as pain in the chest,
      pain in the shoulder or back, radiating pain or numbness in the arms, dyspnea,
      and fatigue. Symptoms were reported for the year before AMI and during the acute
      stage. Logistic regression analyses were used to examine the association between
      prodromal symptoms and acute symptoms and the effect of medical history
      (hypertension, diabetes, and hypercholesterolemia). RESULTS: The self
      administered questionnaire had a 72% response rate; the study included 149 women
      and 384 men diagnosed with first-time AMI. Symptoms occurring during the year
      before AMI included pain in the chest in 45% (240/533), shoulder or back pain in
      51% (270/533), arm pain in 38% (205/533), dyspnea in 33% (176/533), and fatigue
      in 62% (330/533). There were no statistically significant gender differences. The
      risk of experiencing chest symptoms in the acute phase was >5 times higher in
      women who had experienced prodromal symptoms in the chest (adjusted odds ratio
      [OR] = 5.11; 95% CI, 1.38-18.88) and nearly 3 times higher in men (OR = 2.80; 95%
      CI, 1.17-6.70). The risk of experiencing shoulder or back pain was almost 5 times
      higher in men with prodromal shoulder or back pain (OR = 4.96; 95% CI, 3.01
      8.19), but no statistically significant association was found in women. The risk
      of experiencing radiating arm pain or numbness in the acute phase was more than
      doubled in women with prodromal arm pain (OR = 2.68; 95% CI, 1.19-6.20) and more
      than tripled in men with prodromal arm pain (OR = 3.11; 95% CI, 1.90-5.07). The
      risk of experiencing dyspnea in the acute phase was more than doubled in women
      with prodromal dyspnea (OR = 2.67; 95% CI, 1.25-5.71) and >5 times higher in men
      with prodromal dyspnea (OR = 5.73; 95% CI, 3.42-9.62). Finally, the risk of
      fatigue was almost tripled in women (OR = 2.97; 95% CI, 1.28-6.85) and more than
      doubled in men (OR = 2.51; 95% CI, 1.54-4.11). Hypertensive women, but not men,
      were less likely to experience chest symptoms in the acute phase (OR = 0.29; 95%
      CI, 0.10-0.82). CONCLUSIONS: Almost half of the study patients (45%) experienced
      prodromal chest symptoms the year before their first AMI. These prodromal
      symptoms predicted the symptoms that occurred during the acute stage of AMI, with
      some differences between the sexes.

PMID- 19850241
TI  - Symptoms of a first acute myocardial infarction in women and men.
AB  - BACKGROUND: Many studies have compared women and men for symptoms of acute
      myocardial infarction (AMI), but findings have been inconsistent, largely because
      of varying inclusion criteria, different study populations, and different
      methods. OBJECTIVE: The purpose of this study was to analyze gender differences
      in symptoms in a well-defined, population-based sample of women and men who
      experienced a first AMI. METHODS: Information on symptoms was collected from the
      medical charts of all patients with a first AMI, aged 25 to 74 years, who had
      taken part in the INTERGENE (Interplay Between Genetic Susceptibility and
      Environmental Factors for the Risk of Chronic Diseases) study. INTERGENE was a
      population-based research program on risk factors for cardiovascular disease.
      Medical charts were reviewed for each patient to determine the symptoms of AMI,
      and the prevalence of each symptom was compared according to sex. RESULTS: The
      study included 225 patients with a first AMI: 52 women and 173 men. Chest pain
      was the most common symptom, affecting 88.5% (46/52) of the women and 94.8%
      (164/173) of the men, with no statistically significant difference between the
      sexes. Women had significantly higher rates of 4 symptoms: nausea (53.8% [28/52]
      vs 29.5% [51/173]; age-adjusted odds ratio [OR] = 2.78; 95% CI, 1.47-5.25), back
      pain (42.3% [22/52] vs 14.5% [25/173]; OR = 4.29; 95% CI, 2.14-8.62), dizziness
      (17.3% [9/52] vs 7.5% [13/173]; OR = 2.60; 95% CI, 1.04-6.50), and palpitations
      (11.5% [6/52] vs 2.9% [5/173]; OR = 3.99; 95% CI, 1.15-13.84). No significant
      gender differences were found in the proportions of patients experiencing arm or
      shoulder pain, diaphoresis, dyspnea, fatigue, neck pain, abdominal pain,
      vomiting, jaw pain, or syncope/lightheadedness. No significant differences were
      found in the duration, type, or location of chest pain. The medical charts listed
      numerically more symptoms in women than in men; 73.1% (38/52) of the women but
      only 48.0% (83/173) of the men reported >3 symptoms (age-adjusted OR = 3.26; 95%
      CI, 1.62-6.54). CONCLUSIONS: Chest pain is the most common presenting symptom in
      both women and men with AMI. Nausea, back pain, dizziness, and palpitations were
      significantly more common in women. Women as a group displayed a greater number
      of symptoms than did men.

PMID- 19850242
TI  - Gender differences in adiponectin and low-grade inflammation among individuals
      with normal glucose tolerance, prediabetes, and type 2 diabetes.
AB  - BACKGROUND: Women with prediabetes and type 2 diabetes mellitus have a higher
      relative risk of cardiovascular disease than do men. The reason for this is
      unknown. OBJECTIVE: We studied the gender differences in adiponectin and in low
      grade inflammation, measured by high-sensitivity C-reactive protein (hs-CRP) and
      interleukin-1 receptor antagonist (IL-1RA), in individuals with normal glucose
      tolerance, prediabetes, and type 2 diabetes. METHODS: In this population-based,
      cross-sectional study, all individuals born in 1942, 1947, 1952, 1957, and 1962
      in Pieksamaki, East Finland, were recruited for participation. A 75-g oral
      glucose tolerance test and lipid panel were performed, and concentrations of
      adiponectin, hs-CRP, and IL-1RA were measured. The World Health Organization
      diagnostic criteria for diabetes and prediabetes (impaired fasting glucose and/or
      impaired glucose tolerance) were used. Statistical comparisons between men and
      women were performed by a bootstrap-type ANCOVA. RESULTS: The eligible population
      included 1294 middle-aged individuals, and of these, 904 (406 men and 498 women)
      had complete data and were included in the analyses. Absolute adiponectin
      concentrations were significantly higher in women at all levels of glucose
      tolerance (normal, prediabetes, and type 2 diabetes), but the gender ratio (women
      to men) for adiponectin concentrations decreased linearly (P = 0.011) from normal
      glucose tolerance (1.61; 95% CI, 1.48-1.75) to prediabetes (1.57; 95% CI, 1.36
      1.83) and diabetes (1.16; 95% CI, 0.87-1.53). Among participants with normal
      glucose tolerance, no significant difference was found between the sexes in hs
      CRP or IL-1RA. Among patients with prediabetes or diabetes, women had
      significantly higher concentrations than did men for hs-CRP (for prediabetes, 2.0
      vs 1.5 mg/L; ratio, 1.39; 95% CI, 1.04-1.85) and IL-1RA (for prediabetes, 255 vs
      178 pg/mL; ratio, 1.43; 95% CI, 1.121.83). The gender ratios (women to men)
      increased linearly from normal glucose tolerance to prediabetes and type 2
      diabetes for both hs-CRP (P = 0.019) and IL-1RA (P = 0.013). CONCLUSIONS:
      Adiponectin concentrations in women decreased relatively more compared with men
      across individuals with normal glucose tolerance, prediabetes, and type 2
      diabetes, whereas inflammatory markers increased relatively more in women. Higher
      inflammatory stress in women than in men with prediabetes and type 2 diabetes may
      explain their relatively higher cardiovascular disease risk.

PMID- 19850243
TI  - Assessment of gender-specific preventive cardiovascular knowledge among house
      staff: Potential impact on cardiovascular management.
AB  - BACKGROUND: Gender differences in cardiovascular prevention and treatment may be
      related to physicians' level of postgraduate training and gender. OBJECTIVES:
      This study was designed to assess resident physician knowledge concerning general
      and gender-specific preventive cardiology topics and to determine whether there
      were differences in that knowledge based on the physicians' level of postgraduate
      training or gender. METHODS: A 29-item true/false questionnaire was administered
      to residents in a large, university-based internal medicine residency program.
      All questions were drawn from evidence-based practice guidelines, and a subset of
      questions pertained to gender-specific issues in cardiovascular disease
      prevention. Scores on the overall test and gender-specific subset were computed
      as a percentage of correct answers. Differences were compared by postgraduate
      year (PGY) of training and physician gender. RESULTS: Of the 190 eligible
      residents, 159 (88 men, 67 women, 4 not specified) completed the questionnaire.
      Overall test scores differed significantly by PGY (PGY-1, 83.4% correct answers;
      PGY-2, 52.9%; PGY-3, 65.3%; P < 0.001 for each paired comparison), but did not
      differ significantly by physician gender (males, 73.5%; females, 70.0%).
      Performance on gender-specific items also differed by PGY (PGY-1, 72.2% vs PGY-2,
      20.0%; P < 0.001; and PGY-1, 72.2% vs PGY-3, 45.1%; P < 0.001). Knowledge of
      gender-specific preventive cardiology did not differ significantly by physician
      gender (males, 56.4%; females, 49.0%). CONCLUSIONS: Residents in PGY-1 had better
      knowledge of preventive cardiology as assessed using this questionnaire than did
      residents in PGY-2 or PGY-3. Knowledge of general and gender-specific cardiology
      topics was not related to physician gender.

PMID- 19850244
TI  - Gender as a determinant of responses to a self-screening questionnaire on anxiety
      and depression by patients with coronary artery disease.
AB  - BACKGROUND: Because patients with coronary artery disease (CAD) could benefit
      from interventions to decrease psychological distress, it is important to
      identify these individuals. Both salivary cortisol level and the Hospital Anxiety
      and Depression Scale (HADS) are recognized measures of stress/anxiety and
      depression. OBJECTIVES: This study was designed to determine whether there is an
      association between anxiety and depression, as measured by the HADS, and salivary
      cortisol levels among patients with CAD, and whether this association is affected
      by gender. METHODS: All adult residents of Alberta, Canada, undergoing their
      first cardiac catheterization for CAD (>or=50% occlusion of >or=2 coronary
      arteries) were eligible for participation in this study. A 14-question survey
      (the HADS) and 3 saliva-collection devices (a 1-day supply) were sent to the
      participants' home within 1 week of their initial cardiac catheterization.
      Participants were asked to take saliva samples for determination of cortisol
      levels on waking and at 30 and 60 minutes after waking, and then return the
      completed questionnaire and saliva samples using a prepaid express mailing
      envelope. RESULTS: Seventy-one adults (52 men and 19 women) participated in the
      study. Mean (SD) ages were 68.4 (4.6) years for men and 69.1 (4.4) years for
      women. Among the women, significant negative correlations were found between the
      HADS anxiety score and the wake-up and 30-minute cortisol levels (higher HADS
      scores were associated with lower cortisol levels) (all, P < 0.05). Also among
      women, negative correlations were found between the HADS depression score and the
      salivary cortisol values, but the differences were not statistically significant.
      Conversely, among the men, nonsignificant positive correlations were found
      between the HADS anxiety scores and the salivary cortisol levels (higher HADS
      scores were associated with higher cortisol levels), and statistically
      significant positive correlations were observed between the HADS depression
      scores and all 3 salivary cortisol values (all, P < 0.05). CONCLUSIONS: Our
      findings suggest that the HADS is an appropriate screening instrument for anxiety
      and depression in patients with CAD. In particular, the scale appears to be
      sensitive for measuring anxiety in women and depression in men. When the HADS is
      used clinically as a screening tool, it should be examined through a "gender
      based lens.".

PMID- 19850245
TI  - Effects of acute and 2-day genistein treatment on cardiac function and ischemic
      tolerance in ovariectomized rats.
AB  - BACKGROUND: Genistein, a naturally occurring isoflavonic phytoestrogen associated
      with reduced incidence of heart disease, may be a possible alternative treatment
      for postmenopausal women with heart disease. OBJECTIVE: This study examined the
      effects of genistein on in vitro heart function and ischemic tolerance in
      ovariectomized (OVX) Sprague-Dawley rats. METHODS: To examine the acute effects
      of genistein on cardiac function, isolated working hearts were perfused under
      aerobic conditions with increasing concentrations of genistein (10-150 microM). A
      separate group of OVX rats was used to assess ischemic tolerance: treated rats
      received genistein (250 mg/kg, dissolved in 200 microL dimethyl sulfoxide [DMSO])
      injected once daily for 2 days, and control rats received DMSO only. After
      treatment, hearts were perfused for 30 minutes under aerobic conditions and then
      subjected to 20 minutes of global no-flow ischemia by clamping the preload and
      afterload lines, followed by 30 minutes of reperfusion. RESULTS: Genistein was
      associated with improvements in mechanical function in OVX rat hearts (n = 5)
      with maximum increases in contractility (259 mm Hg/sec above baseline) and
      cardiac output (7 mL/min above baseline) observed with 30 microM of genistein
      (both, P < 0.05). Relative to baseline, genistein-treated hearts (n = 5) also had
      greater ischemic tolerance than did control hearts (n = 6) and significant
      improvements in mean (SEM) recovery of contractility (to 75.0% [9.7%] of
      preischemic function; P < 0.05) and cardiac output (to 48.8% [12.3%] of
      preischemic function; P < 0.05) after reperfusion. These effects occurred without
      significant changes in myocardial levels of nonprotein thiols or thiobarbituric
      acid reactive substances, although a reduction in mean glucose transporter
      protein 4 content (13.2% [2.7%]; P < 0.05) was observed in genistein-treated
      hearts. No significant changes in blood pressure were observed with genistein.
      CONCLUSIONS: Despite the lack of significant changes in physical characteristics,
      2-day treatment with genistein was associated with significant cardioprotective
      effects in OVX rats, suggesting a potential therapeutic role in postmenopausal
      women.

PMID- 19850246
TI  - Effects of estradiol on renal cyclic guanosine monophosphate and oxidative stress
      in spontaneously hypertensive rats.
AB  - BACKGROUND: Evidence suggests that estradiol offers protection against the
      development of cardiovascular and renal pathologies, although the mechanisms
      involved are still under investigation. The nitric oxide (NO) pathway regulates
      blood pressure and kidney function, and estradiol is associated with increases in
      NO bioavailability. We hypothesized that in female spontaneously hypertensive
      rats (SHRs), estra-diol increases NO bioavailability, activates the NO synthase
      (NOS) pathway, and suppresses superoxide production compared with rats that
      underwent ovariectomy (OVX). OBJECTIVE: The goal of this study was to determine
      whether estradiol regulates the NO/cyclic guanosine monophosphate (cGMP) pathway
      and superoxide levels in the kidneys of female SHR. METHODS: Three types of SHRs
      were studied: gonad-intact females, OVX rats, and OVX rats with estra-diol
      replacement (OVX+E). Renal cortical cGMP levels were measured to assess NO
      bioavailability. NOS enzymatic activity, NOS protein expression, basal superoxide
      production, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      activity were measured in the renal cortex. RESULTS: Fifty-six SHRs were included
      in the study (17 intact females, 21 OVX rats, 18 OVX+E rats). Mean (SEM) cGMP
      levels were significantly lower in the renal cortex of OVX rats (0.03 [0.008]
      pmol/mg, n = 5) than in intact females (0.1 [0.02] pmol/mg, n = 6; P < 0.05), and
      estradiol restored cGMP levels to those seen in intact females (0.1 [0.01]
      pmol/mg, n = 5; P < 0.05). Despite a decrease in cGMP following OVX, renal
      cortical NOS activity, NOS1 and NOS3 protein expression, and the phosphorylation
      status of NOS3 were comparable among the 3 groups (n = 7-9 per group). However,
      mean basal superoxide production in the renal cortex was higher in OVX rats (3.2
      [0.3] cpm/mg, n = 12) than in intact females (1.9 [0.3] cpm/mg, n = 8; P < 0.05)
      and lower in OVX+E rats (1.3 [0.3] cpm/mg, n = 9; P < 0.05). Mean NADPH oxidase
      activity was comparable in the renal cortex of intact females and OVX rats (81
      [4] and 83 [12] cpm/35 microg, respectively [n = 5 per group]). OVX+E rats had
      significantly lower mean renal cortical NADPH oxidase activity than did rats in
      the other groups (45 [6] cpm/35 microg, n = 6; P < 0.05), and the decrease in
      activity was accompanied by a decrease in p22(phox) protein expression.
      CONCLUSIONS: In vivo manipulations of estradiol levels influenced renal cortical
      NO bioavailability, as assessed indirectly by cGMP measurements. The decrease in
      cGMP following OVX was not due to alterations in the activity or expression of
      NOS.

PMID- 19850247
TI  - Systems of care for ST-segment elevation myocardial infarction: impact of
      different models on clinical outcomes.
AB  - ST-segment elevation myocardial infarction (STEMI) is one of the greatest medical
      emergencies, for which organization of care has a determinant impact on patient
      outcomes. The purpose of this paper is to review systems of care for STEMI
      patients. Although primary percutaneous coronary intervention (PCI) is the
      preferred option for patients with STEMI, offering easy and emergent access to
      this procedure often remains difficult because of geographic and diverse
      structural difficulties. intravenous fibrinolysis, especially when administered
      early after symptom onset and as part of a pharmacoinvasive strategy (i.e.,
      followed by rapid coronary angiography with PCI when necessary), offers a
      reasonable therapeutic option in selected cases and has yielded satisfactory
      clinical results. Network organization is central for optimizing patient care at
      the acute stage of myocardial infarction. This review describes different
      clinical experiences with network implementation both in Europe and in North
      America. In all instances, early recognition of STEMI and, particularly in the
      pre-hospital setting, shortening time delays is central for the achievement of
      optimal clinical results. Overall, the encouraging results described in the
      models presented here, as diverse as they might be, should be an encouragement to
      promote and implement regional protocols according to the specific local
      constraints and to monitor their effectiveness by recording simple quality
      indicators in ongoing registries.

PMID- 19850248
TI  - 1-year survival in a randomized trial of facilitated reperfusion: results from
      the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop
      Events) trial.
AB  - OBJECTIVES: The aim of this report was to evaluate 12-month outcomes of
      facilitated percutaneous coronary intervention (PCI) in the FINESSE (Facilitated
      Intervention with Enhanced Reperfusion Speed to Stop Events) trial. BACKGROUND:
      Treatment delays remain common for patients with primary PCI leading to studies
      evaluating possible benefit of "facilitated" PCI. In the FINESSE trial, no
      reduction in the 90-day primary ischemic end point and an increase in bleeding
      were observed with both facilitated approaches, although modest favorable trends
      were seen for some patient subgroups. METHODS: A total of 2,452 patients with ST
      segment elevation myocardial infarction (MI) and anticipated 1 to 4 h delay until
      catheterization were randomized to reduced-dose reteplase + abciximab, abciximab
      alone, or placebo, followed by expedited primary PCI. Placebo-treated patients
      received abciximab in the cath lab. One-year mortality was a pre-specified
      secondary end point. RESULTS: One-year mortalities in the 3 groups noted in the
      preceding text were 6.3%, 7.4%, and 7.0%, respectively (p = NS), representing
      1.1%, 1.9%, and 2.5% increments since the 90-day outcome (p = 0.053 for
      combination treatment vs. primary PCI). A favorable trend with combination
      treatment was seen for patients with anterior MI (p = 0.09), but no other
      specified groups benefited or tended to benefit. Independent baseline correlates
      of 1-year mortality were systolic blood pressure <100 mm Hg, prior MI, age,
      Killip class >1, anterior MI, body mass index < or =25 kg/m(2), heart rate >100
      beats/min, and no statin use. CONCLUSIONS: These results suggest that widespread
      utilization of the facilitated approaches tested cannot be justified, but that
      high-risk patient groups such as patients with anterior MI may deserve further
      study. (The FINESSE trial; NCT00046228).

PMID- 19850249
TI  - Benefit of facilitated percutaneous coronary intervention in high-risk ST-segment
      elevation myocardial infarction patients presenting to nonpercutaneous coronary
      intervention hospitals.
AB  - OBJECTIVES: We hypothesized that patients most likely to benefit would be those
      at high risk with a shorter duration of acute ischemia and who required transfer
      for percutaneous coronary intervention (PCI). BACKGROUND: The FINESSE
      (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) study
      failed to demonstrate an improvement in the 90-day composite clinical end point
      of early treatment with abciximab plus half-dose reteplase (combination
      facilitated PCI) or abciximab alone. METHODS: We performed a retrospective
      analysis of 2,452 patients in this double-blind, placebo-controlled study.
      Patients were stratified by Thrombolysis In Myocardial Infarction (TIMI) risk
      score for ST-segment elevation myocardial infarction (STEMI), presentation to a
      spoke (no PCI available) or hub site, and symptom-to-randomization time. Outcomes
      included the primary composite end point of death, ventricular fibrillation after
      48 h, cardiogenic shock, and congestive heart failure through day 90 as well as 1
      year mortality. RESULTS: Mortality for all patients at 1 year was directly
      related to TIMI risk score (23 of 1,223 = 1.9% in patients with score <3 and 145
      of 1,229 = 11.8% with score > or =3, p < 0.001). Patients with TIMI risk score >
      or =3 and presentation to a spoke site with a symptom-to-randomization time < or
      =4 h had significantly better 1-year survival if treated with combination
      facilitated PCI (hazard ratio [HR]: 0.351, p = 0.01) as well as 90-day composite
      outcome (HR: 0.45, p = 0.009). A trend for improved survival was also observed in
      patients with TIMI score > or =3 and spoke site alone (HR: 0.549, p = 0.06).
      CONCLUSIONS: Facilitation of PCI with a combination of abciximab and half-dose
      reteplase improved survival at 1 year in high-risk patients presenting to a spoke
      hospital with symptom-to-randomization time < or =4 h. Further prospective study
      of facilitated PCI in this subgroup of patients is warranted.

PMID- 19850250
TI  - The impact of place of enrollment and delay to reperfusion on 90-day post
      infarction mortality in the ASSENT-4 PCI trial: assessment of the safety and
      efficacy of a new treatment strategy with percutaneous coronary intervention.
AB  - OBJECTIVES: We have performed a retrospective analysis of the data stratified by
      time to treatment and by enrollment site: percutaneous coronary intervention
      hospitals (PCIH), nonpercutaneous coronary intervention hospitals (NoPCIH), or in
      a pre-hospital setting (PreH). BACKGROUND: The ASSENT-4 PCI (Assessment of the
      Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary
      Intervention) trial intended to test the hypothesis that in ST-segment elevation
      myocardial infarction (STEMI) patients an upfront fibrinolytic bolus before PCI
      ("facilitated PCI") compared with primary PCI would benefit STEMI patients facing
      a long pre-PCI delay. METHODS: Seven hundred forty-nine patients (45%) presented
      directly to PCIH, 578 (34%) presented to NoPCIH, and 334 (20%) were randomized
      and initially treated in the PreH setting. RESULTS: Patients in the PreH
      facilitated group had the shortest delays (pain-to-fibrinolytic treatment 125
      min) and the lowest 90-day mortality (3.1%). Among patients randomized to primary
      PCI, the shortest time from pain to first balloon was similarly in the PreH group
      (223 min). They had the lowest mortality of the primary PCI patient groups
      (4.1%). The highest mortality (8.4%) was in patients presenting to a PCIH and
      assigned to the facilitated strategy. Their pain-to-lysis time was 174 min and
      pain-to-PCI time 266 min (or 92 min after lysis). CONCLUSIONS: Few patients fit
      the target population, long delays to PCI for whom facilitated PCI was designed.
      Patients treated early after pain onset in the PreH setting do well after a
      facilitated approach. Despite limitations of post hoc subgroup analysis, these
      observations suggest caution in extrapolating the results of the ASSENT-4 trial
      to the "real world" where many patients might have potentially short pain-to
      fibrinolysis time but are facing a long transport time to primary PCI.

PMID- 19850251
TI  - The ideal reperfusion strategy for the ST-segment elevation myocardial infarction
      patient with expected delay to percutaneous coronary intervention: paradise lost
      or paradise renamed?

PMID- 19850253
TI  - Outcomes among patients with non-ST-segment elevation myocardial infarction
      presenting to interventional hospitals with and without on-site cardiac surgery.
AB  - OBJECTIVES: The goals of this analysis were: 1) to evaluate outcomes among non-ST
      segment elevation myocardial infarction (NSTEMI) patients presenting to hospitals
      with on-site cardiac surgery (OHS hospitals) and without on-site cardiac surgery
      (No-OHS hospitals); and 2) to specifically examine outcomes among the subset of
      NSTEMI patients undergoing percutaneous coronary intervention (PCI). BACKGROUND:
      Whether backup cardiac surgery improves outcomes among NSTEMI patients or is
      simply a marker of better adherence to guideline recommendations is unknown.
      METHODS: The NRMI (National Registry of Myocardial Infarction) enrolled 100,071
      NSTEMI patients from 2004 to 2006. Outcomes were evaluated in the population as a
      whole and in propensity-matched analyses in the entire population and in the
      subset of patients undergoing PCI. RESULTS: In-hospital mortality was
      significantly lower at OHS hospitals (5.0% vs. 8.8%, p < 0.001). Patients
      presenting to OHS hospitals were significantly more likely to receive aspirin,
      beta-blockers, and statins (p < 0.05 for all) and to undergo PCI (38.4% vs.
      14.1%, p < 0.001). In the propensity-matched model, the difference in mortality
      remained significant (5.9% vs. 8.5%, p < 0.001). After adjusting for differences
      in medications administered within 24 h of arrival and hospital characteristics,
      the difference in mortality was nearly attenuated (hazard ratio: 0.89, 95%
      confidence interval: 0.79 to 1.00, p = 0.050). When the propensity-matched model
      was restricted to patients undergoing PCI, there was no significant difference in
      mortality (1.3% vs. 1.0%, p = 0.51). CONCLUSIONS: NSTEMI patients presenting to
      No-OHS hospitals have significantly higher mortality. This appears to be due to
      both modifiable (lower use of guideline-recommended medications) and
      nonmodifiable factors (hospital size, myocardial infarction volume). In a
      propensity-matched analysis of patients undergoing PCI for NSTEMI, there was no
      significant difference in mortality.

PMID- 19850252
TI  - Randomized comparison of primary percutaneous coronary intervention with combined
      proximal embolic protection and thrombus aspiration versus primary percutaneous
      coronary intervention alone in ST-segment elevation myocardial infarction: the
      PREPARE (PRoximal Embolic Protection in Acute myocardial infarction and
      Resolution of ST-Elevation) study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effectiveness of
      combined proximal embolic protection with thrombus aspiration (Proxis Embolic
      Protection System [St. Jude Medical, St. Paul, Minnesota]) in ST-segment
      elevation myocardial infarction patients. BACKGROUND: Embolization during primary
      percutaneous coronary intervention (PCI) may result in microvascular obstruction,
      reduced myocardial perfusion, and impaired prognosis. METHODS: Two hundred eight
      four patients were randomized to primary PCI with the Proxis system versus
      primary PCI alone after angiography. The primary end point was the occurrence of
      complete (> or =70%) ST-segment resolution (STR) at 60 min measured by continuous
      ST-segment Holter. RESULTS: There was no significant difference in the occurrence
      of the primary end point (80% vs. 72%, p = 0.14). However, immediate complete STR
      (at time of last contrast) occurred in 66% of Proxis-treated patients and 50% in
      control patients (absolute difference, 16.3%; 95% confidence interval: 4.3% to
      28.2%; p = 0.009). A significant lower ST-segment curve area (0 to 3 h after
      primary PCI) was observed in the Proxis arm (5,192 microV/min vs. 6,250
      microV/min, p = 0.037). Major adverse cardiac and cerebral events at 30 days
      occurred with similar frequency in both groups (6 vs. 10). CONCLUSIONS: There was
      no significant difference in complete STR at 60 min in this proof-of-concept
      study. However, we observed a significant difference in immediate complete STR in
      Proxis-treated patients, better STR at later time points, and a reduction of
      electrocardiogram injury current over time, compared with control patients. The
      results suggest that primary PCI with the Proxis system may lead to better
      immediate microvascular flow in ST-segment elevation myocardial infarction
      patients. (The PREPARE Study; ISRCTN71104460).

PMID- 19850254
TI  - Non-ST-segment elevation myocardial infarction treated at hospitals with and
      without on-site cardiac surgery: what is the important point?

PMID- 19850255
TI  - Impact of diabetes mellitus on the treatment effect of percutaneous or surgical
      revascularization for patients with unprotected left main coronary artery
      disease: a subgroup analysis of the MAIN-COMPARE study.
AB  - OBJECTIVES: This study sought to investigate whether the outcome of drug-eluting
      stent (DES) treatment and that of coronary artery bypass grafting (CABG) differed
      in diabetic and nondiabetic patients with unprotected left main coronary artery
      (LMCA) disease. BACKGROUND: Diabetes mellitus has been shown to be a risk factor
      for adverse events and a major determinant in selection of a revascularization
      strategy in patients with multivessel or LMCA disease. METHODS: A total of 1,474
      patients with unprotected LMCA stenosis who received DES (n = 784) or underwent
      CABG (n = 690) were examined. We compared the effects of these 2 treatments on
      long-term clinical outcomes (death; the composite of death, Q-wave myocardial
      infarction [MI], or stroke; and target vessel revascularization [TVR]), according
      to diabetic status. RESULTS: After adjustment of covariates, the risk of death
      (hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.62 to 1.46, p = 0.83)
      and the composite of death, Q-wave MI, or stroke (HR: 0.96, 95% CI: 0.65 to 1.42,
      p = 0.85) at 3 years were similar in the DES and CABG groups. However, the rate
      of TVR was significantly higher in the DES group (HR: 4.31, 95% CI: 2.28 to 8.15,
      p < 0.001). These trends were consistent in both diabetic and nondiabetic
      patients. We also did not observe a diabetes-associated excess risk of death
      (p(interaction) = 0.90 and 0.16), or a composite of death, Q-wave MI, or stroke
      (p(interaction) = 0.68 and 0.93), or TVR (p(interaction) = 0.23 and 0.92),
      between patients receiving either treatment. CONCLUSIONS: The prognostic impact
      of diabetes on long-term treatment with DES or CABG for patients with unprotected
      LMCA disease was minimal.

PMID- 19850256
TI  - Diabetes mellitus does not unsweeten left main intervention.

PMID- 19850257
TI  - Clinical and angiographic outcomes in diabetics from the ENDEAVOR IV trial:
      randomized comparison of zotarolimus- and paclitaxel-eluting stents in patients
      with coronary artery disease.
AB  - OBJECTIVES: The aim of this study was to examine outcomes related to the use of
      the Endeavor zotarolimus-eluting stent (ZES) (Medtronic CardioVascular, Santa
      Rosa, California) compared with the TAXUS paclitaxel-eluting stent (PES) (Boston
      Scientific Corp., Natick, Massachusetts) in the 477 patients with diabetes
      mellitus (DM) enrolled in the randomized ENDEAVOR IV (Randomized Comparison of
      Zotarolimus- and Paclitaxel-Eluting Stents in Patients with Coronary Artery
      Disease) trial. BACKGROUND: Percutaneous coronary intervention (PCI) in diabetic
      patients is associated with increased rates of restenosis-related end points
      compared with PCI in nondiabetic patients. Although ZES has been associated with
      similar clinical efficacy compared with PES in the overall trial population of
      the ENDEAVOR IV trial, whether these results are maintained in the higher-risk
      restenosis subgroup of patients with DM has not been determined. METHODS:
      Clinical and angiographic outcomes were compared according to randomized
      treatment assignment to either ZES or PES. RESULTS: Baseline characteristics were
      similar among ZES (n = 241) and PES (n = 236) diabetic patients, with slightly
      longer lesion lengths in PES-treated patients (12.9 mm vs. 14.0 mm, p = 0.041).
      Among the 86 DM patients assigned to routine angiographic follow-up (18% of the
      overall DM cohort), in-stent percent diameter stenosis at 8 months was greater
      among ZES-treated patients (32.9 vs. 21.1, p = 0.023), with a trend toward higher
      in-stent late loss. One-year clinical outcomes were similar among DM patients
      treated with either ZES or PES (target vessel failure: 8.6% vs. 10.8%, p = 0.53;
      target lesion revascularization: 6.9% vs. 5.8%, p = 0.70; target vessel
      revascularization: 8.6% vs. 9.4%, p = 0.87). There were no significant
      interactions between DM status and stent type with respect to the outcomes
      measured, and the relative efficacy/safety of ZES and PES were similar among
      insulin- and noninsulin-requiring subgroups. CONCLUSIONS: One-year clinical
      outcomes were similar among DM patients treated with ZES and PES in the ENDEAVOR
      IV trial. These findings parallel the overall trial results, which demonstrated
      similar efficacy and safety of ZES and PES for single de novo coronary lesions.

PMID- 19850259
TI  - A generation 2.5 drug-eluting stent?

PMID- 19850258
TI  - Clinical and angiographic results with the next-generation resolute stent system:
      a prospective, multicenter, first-in-human trial.
AB  - OBJECTIVES: The RESOLUTE trial examined the safety and efficacy of a next
      generation zotarolimus-eluting coronary stent, Resolute (Medtronic CardioVascular
      Inc., Santa Rosa, California). BACKGROUND: Revascularization benefits associated
      with current drug-eluting stents are often diminished in the presence of complex
      coronary lesions and in certain patient cohorts. Resolute uses a new proprietary
      polymer coating that extends the duration of drug delivery to match the longer
      healing duration often experienced in more complex cases. METHODS: The RESOLUTE
      trial was a prospective, nonrandomized, multicenter study of the Resolute stent
      in 139 patients with de novo coronary lesions with reference vessel diameters >
      or =2.5 and < or =3.5 mm and lesion length > or =14 and < or =27 mm. The primary
      end point was 9-month in-stent late lumen loss by quantitative coronary
      angiography. Secondary end points included major adverse cardiac events (MACE) at
      30 days, 6, 9, and 12 months; acute device, lesion, and procedure success; and 9
      month target vessel failure (TVF), target lesion revascularization (TLR), stent
      thrombosis, neointimal hyperplastic (NIH) volume, and percent NIH volume
      obstruction. RESULTS: The 9-month in-stent late lumen loss was 0.22 +/- 0.27 mm.
      Cumulative MACE were 4.3%, 4.3%, 7.2%, and 8.7% at 30 days, 6, 9, and 12 months,
      respectively. Acute lesion, procedure, and device success rates were 100.0%,
      95.7%, and 99.3%, respectively. At 9 months, TLR was 0.0%, TVF was 6.5%, stent
      thrombosis was 0.0%, NIH volume was 6.55 +/- 7.83 mm(3), and percent NIH volume
      obstruction was 3.73 +/- 4.05%. CONCLUSIONS: In this feasibility study, the
      Resolute stent demonstrated low in-stent late lumen loss, minimal neointimal
      hyperplastic ingrowth, low TLR, no stent thrombosis, and acceptable TVF and MACE.
      (The RESOLUTE Clinical Trial; NCT00248079).

PMID- 19850260
TI  - Optimal stent-sizing with intravascular ultrasound contributes to complete
      neointimal coverage after sirolimus-eluting stent implantation assessed by
      angioscopy.
AB  - OBJECTIVES: The aim of this study was to explore the determinants of neointimal
      coverage after sirolimus-eluting stent (SES). BACKGROUND: Although SES has
      significantly reduced in-stent restenosis by inhibiting neointimal hyperplasia,
      insufficient neointimal coverage after stenting might result in adverse outcomes.
      METHODS: We evaluated 28 SES lesions with both angioscopy and intravascular
      ultrasound (IVUS). Quantitative assessments of the lesions and stent expansion
      were performed by IVUS at the time of stent implantation, and degree of
      neointimal coverage was judged by angioscopy at follow-up (11 +/- 6 months)
      whether the stent struts were embedded by the neointima ("complete/incomplete"
      neointimal coverage). RESULTS: "Complete" coverage was identified in 10 (36%),
      and "incomplete" coverage was identified in 18 (64%). Time from the stenting to
      angioscopy as well as the lesion and procedural characteristics were similar
      between the complete and incomplete coverage groups. The IVUS parameters were
      also similar, except for the final minimum stent cross-sectional area (CSA) (7.0
      +/- 1.8 mm(2) in complete vs. 5.3 +/- 1.9 mm(2) in incomplete, p = 0.02) and
      lumen CSA at the distal reference site (6.1 +/- 1.4 mm(2) in complete vs. 4.9 +/-
      1.2 mm(2) in incomplete, p = 0.02). The ratio of the stent area to the vessel
      area was significantly larger in the complete coverage than in the incomplete
      coverage group (0.52 +/- 0.11 vs. 0.39 +/- 0.09, p = 0.002). CONCLUSIONS:
      Adequate stent sizing relative to the vessel size might contribute to the
      angioscopically complete neointimal coverage after SES implantation.

PMID- 19850261
TI  - Optimal stent expansion and complete neointimal coverage: does this association
      make sense?

PMID- 19850262
TI  - Intravascular ultrasound assessment of the incidence and predictors of edge
      dissections after drug-eluting stent implantation.
AB  - OBJECTIVES: We used intravascular ultrasound (IVUS) to assess incidence,
      predictors, morphology, and angiographic findings of edge dissections after drug
      eluting stent (DES) implantation. BACKGROUND: DES implantation strategies differ
      compared with bare-metal stenting; coronary dissections after DES implantation
      have not been well studied. METHODS: We studied 887 patients with 1,045 non-in
      stent restenosis lesions in 977 native arteries undergoing DES implantation with
      IVUS imaging. RESULTS: Eighty-two dissections were detected; 51.2% (42 of 82)
      involved the proximal and 48.8% (40 of 82) the distal stent edge. Residual plaque
      area (8.0 +/- 4.3 mm(2) vs. 5.2 +/- 3.0 mm(2), p < 0.0001); plaque burden (52.2
      +/- 11.7% vs. 36.2 +/- 15.3%, p < 0.0001); plaque eccentricity (8.4 +/- 5.5 vs.
      4.0 +/- 3.4, p < 0.0001); and stent edge symmetry (1.2 +/- 0.1 vs. 1.1 +/- 0.1, p
      = 0.02) were larger; plaque burden > or =50% was more frequent (62.0% vs. 17.2%,
      p < 0.0001); calcium deposits (52.1% vs. 35.2%, p = 0.03) more common; and lumen
      to-stent-edge-area ratio (0.9 +/- 0.2 vs. 1.0 +/- 0.2, p < 0.0001) was smaller in
      the edge dissection group compared with the nondissection group. Intramural
      hematomas occurred in 34.1% (28 of 82) of dissections. When compared with
      nonhematoma dissections, residual plaque and media area (6.4 +/- 2.5 mm(2) vs.
      8.9 +/- 4.6 mm(2), p = 0.04) was smaller, and stent edges less asymmetric (1.1 +/
      0.1 vs. 1.2 +/- 0.1, p = 0.009) in the dissection with hematoma group.
      Independent predictors of any stent edge dissection were residual plaque
      eccentricity (odds ratio [OR]: 1.4, p = 0.02), lumen-to-stent-edge-area ratio
      (OR: 0.0, p = 0.007), and stent edge symmetry (OR: 1.2, p = 0.02 for each 0.01
      increase). CONCLUSIONS: IVUS identified edge dissections after 9.2% of DES
      implantations. Residual plaque eccentricity, lumen-to-stent-edge-area ratio, and
      stent edge symmetry predicted coronary stent edge dissections. Dissections in
      less diseased reference segments more often evolved into an intramural hematoma.

PMID- 19850263
TI  - Bone marrow-derived B cells preserve ventricular function after acute myocardial
      infarction.
AB  - OBJECTIVES: In view of evidence that mature cells play a role in modulating the
      stem cell niche and thereby stem cell potential and proliferation, we
      hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion
      subfraction may have particular potency in promoting hematopoietic or resident
      stem cell-induced cardiac repair post-infarction. BACKGROUND: Treatment of acute
      myocardial infarction (MI) with BM MNC infusion has shown promise for improving
      patient outcomes. However, clinical data are conflicting, and demonstrate modest
      improvements. BM MNCs consist of different subpopulations including stem cells,
      progenitors, and differentiated leukocytes. METHODS: Stem cells (c-kit+) and
      subsets of mature cells including myeloid lineage, B and T-cells were isolated
      from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline
      echocardiography then coronary artery ligation; 1 x 10(6) cells (enriched
      subpopulations or combinations of subpopulations of BM MNC) or saline was
      injected into ischemic and ischemic border zones. Cell subpopulations were either
      injected fresh or after overnight culture. After 2 weeks, animals underwent
      follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte
      proliferation and apoptosis. RESULTS: Fractional ventricular diameter shortening
      was significantly improved compared with saline (38 +/- 3.2%) when B cells alone
      were injected fresh (44 +/- 3.0%, p = 0.035), or after overnight culture (51 +/-
      2.9%, p < 0.001), or after culture with c-kit+ cells (44 +/- 2.4%, p = 0.062). B
      cells reduced apoptosis at 48 h after injection compared with control cells (5.7
      +/- 1.2% vs. 12.6 +/- 2.0%, p = 0.005). CONCLUSIONS: Intramyocardial injection of
      B cells into early post-ischemic myocardium preserved cardiac function by
      cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or
      suppressed cardioprotection conferred by an enriched B cell population.

PMID- 19850264
TI  - Feasibility, safety, and efficacy of a novel polymeric pimecrolimus-eluting
      stent: traditional pre-clinical safety end points failed to predict 6-month
      clinical angiographic results.
AB  - OBJECTIVES: The aim of this study was to determine the safety and efficacy of a
      novel pimecrolimus-eluting stent in a porcine coronary model and in a phase I
      clinical trial. BACKGROUND: Rapamycin- and paclitaxel-eluting stents reduce the
      need for repeat intervention by limiting neointimal hyperplasia but might cause
      delayed healing, pre-disposing patients to late stent thrombosis. Because
      inflammation plays a key role in restenosis, pimecrolimus, an anti-inflammatory
      drug, might reduce restenosis without adversely affecting re-endothelialization.
      METHODS: We evaluated a novel polymeric pimecrolimus-eluting stent covered with a
      thin parylene C diffusion barrier in a porcine coronary model and in a phase I
      human clinical trial. The clinical study was a prospective, nonrandomized, first
      in-human hypothesis-generating study that enrolled 15 patients who had a single
      de novo native coronary stenosis. RESULTS: At 28 days and 3 months in the porcine
      model, histopathologic indicators predicted safety and biocompatibility when
      stents coated with polymer only, drug only, and 2 drug-polymer formulations were
      compared with bare-metal stents (BMS). In the phase I clinical trial, 15 patients
      had successful implantation of pimecrolimus-eluting stents. By 6 months, no
      patient suffered death, myocardial infarction, or stent thrombosis. However, the
      angiographic restenosis (61%), mean late loss (1.44 mm), and repeat target lesion
      revascularization (53%) were significantly higher than historical BMS controls.
      Whereas the primary end point was percent volume obstruction, restenosis was so
      severe that operators performed intravascular ultrasound examination in only 6
      patients. CONCLUSIONS: Pimecrolimus-eluting stents induced an exaggerated
      neointimal hyperplasia at 6 months in comparison with historical controls.

PMID- 19850265
TI  - Do we really understand pimecrolimus?

PMID- 19850266
TI  - Health Care Reform Bill H. R. 3200--America's Affordable Health Choices Act: what
      is missing?

PMID- 19850267
TI  - Cocaine-induced coronary artery dissection.

PMID- 19850268
TI  - "If you have a heart attack, just cough".

PMID- 19850269
TI  - [Unusual foreign body on mouth floor].

PMID- 19850270
TI  - [Occupation as a risk factor for oral and pharyngeal cancer].
AB  - INTRODUCTION AND OBJECTIVES: Oral and pharyngeal cancers represent the fifth most
      common cancer type and the seventh cause of deaths by cancer worldwide. Few
      studies have assessed the risks associated with occupational exposure and in many
      cases the results are contradictory. The objective of this study is to determine
      the association between occupational exposure to carcinogenic substances and risk
      of oral and pharyngeal cancer (including nasopharynx and hypopharynx) through a
      systematic review. MATERIAL AND METHODS: A literature search was carried out in
      MEDLINE (PubMed) and EMBASE. The articles were selected by two independent
      investigators on the basis of inclusion and exclusion criteria (sample size,
      publication type, etc.). RESULTS: 10 original articles were included, all with a
      case-control design. The results showed that a prolonged exposure to formaldehyde
      may increase the risk of nasopharyngeal and hypopharyngeal cancer, whilst other
      chemical products were not associated with these tumours. The exposure to
      different types of particles (such as wood dust in nasopharyngeal cancer) and
      smoke of various origins has also been associated with several oral and
      pharyngeal tumours. CONCLUSIONS: The literature reviewed shows that occupational
      exposure to formaldehyde may be associated with an increased risk of
      nasopharyngeal and hypopharyngeal cancer. The results regarding other
      occupational exposures are not consistent, therefore additional studies with more
      statistical power and better design are needed to ascertain if occupation is
      really a relevant risk factor for these types of cancer.

PMID- 19850271
TI  - [Nasosinusal schwannoma].
AB  - Schwannomas are tumours which grow from the most external layer of the peripheral
      nerves. They can appear in any part of the human anatomy, but are especially
      common in the head and neck region. Within this area, the most frequent location
      is the VIII cranial nerve (80%). Treatment is surgical.

PMID- 19850272
TI  - [Hemangioma of the nasal fossa in infants].
AB  - Hemangiomas in infancy are the most frequent benign tumors of the head and neck
      in children. However, intranasal location is very rare. By obstructing the entire
      nasal fossa, it produces a problem of breathing difficulty in the neonatal
      period, which leads to therapeutic measures being taken in the first months of
      life. We present a patient who was born with intranasal hemangioma, we study the
      various therapeutic options and we expose the final resolution of the case, which
      was vaporization using CO(2) laser.

PMID- 19850273
TI  - [Tensor veli palatini and tensor tympani muscles: anatomical, functional and
      symptomatic links].
AB  - INTRODUCTION AND OBJECTIVES: Temporomandibular disorders are associated with
      symptoms such as tinnitus, vertigo, sensation of hearing loss, ear fullness and
      otalgia. The connection and dysfunction of the tensor tympani and tensor veli
      palatini muscles seems to be associated with the aforementioned symptoms. We seek
      to demonstrate and explain this connection through the morphometry of these
      structures. METHODS: We studied 22 paired blocks and 1 left side of human
      temporal bone. Digital measurements were made of the tensor tympani muscles and
      stapes. RESULTS: The average length of the stapedial muscle was 5.8 mm SD 0.61,
      and that of the tensor tympani was 19.69 mm SD 1.07. Anatomical connections were
      found in all the samples between the tensor veli palatini muscles through a
      common tendon. CONCLUSIONS: There is a need for an interdisciplinary management
      between physician and specialized dentist in cases of craniofacial pain.

PMID- 19850274
TI  - [Methodology for evaluation of malignancy screening in surgical thyroid gland
      disease].
AB  - INTRODUCTION: We review a methodology for detection of malignancy in thyroid
      gland surgery, comparing clinical exploration, ultrasonography, gammagraphy, fine
      needle aspiration (FNA) and extemporaneous biopsy with the definitive
      pathological results. MATERIAL AND METHODS: We carried out a retrospective study
      on a sample of 433 (N=433) patients who had been intervened due to thyroid gland
      disease at the same ENT centre between 1999 and 2004. We collected information
      focusing on the characteristics of cervical exploration, ultrasonography,
      gammagraphy, FNA, extemporaneous biopsy and definitive pathological results.
      RESULTS: With N=433, the male/female ratio was approximately 1/9 (m/f 1/9), the
      average age was 45.5 years, with a range between 13 and 87 years, and with 20.3%
      of referred family history of thyroid gland disease; the cervical exploration,
      ultrasonography ang gammagraphy were not good tests for the screening of
      malignancy; FNA and extemporaneous biopsy offered 74% and 81% of sensitivity
      (Se), and 73% and 92% of specificity (Sp) in the detection of malignancy. The
      specific sensitivities towards papillary carcinoma of FNA and extemporaneous
      biopsy were 81% and 88%, whilst for follicular carcinoma they were 66% and 62.5%,
      respectively. CONCLUSIONS: FNA has good sensitivity in clinical suspicion of
      thyroid papillary carcinoma, although it should be complemented by extemporaneous
      biopsy due to its better specificity. In the case of follicular carcinoma there
      is a tendency towards conservative treatment, without carrying out extemporaneous
      biopsy previously and with reintervention in case of definitive malignancy.

PMID- 19850275
TI  - Safety of influenza vaccination during pregnancy.
AB  - The Centers for Disease Control and Prevention Advisory Committee on Immunization
      Practices recommends routine influenza vaccination for all women who are or will
      be pregnant during the influenza season. During seasonal influenza epidemics,
      during previous pandemics, and with the current influenza A (H1N1) pandemic,
      pregnancy places otherwise healthy women at increased risk for serious
      complications from influenza, including death. Inactivated influenza vaccine can
      be safely and effectively administered during any trimester of pregnancy. No
      study to date has demonstrated an increased risk of either maternal complications
      or adverse fetal outcomes associated with inactivated influenza vaccination.
      Moreover, no scientific evidence exists that thimerosal-containing vaccines are a
      cause of adverse events among children born to women who received influenza
      vaccine during pregnancy. In this article, we review the evidentiary basis for
      the recommendation of vaccination of all women who will be pregnant during the
      influenza season and safety data of influenza vaccination during pregnancy.

PMID- 19850276
TI  - An automated method for the determination of the sFlt-1/PIGF ratio in the
      assessment of preeclampsia.
AB  - OBJECTIVE: The angiogenic and antiangiogenic factors soluble fms-like tyrosine
      kinase (sFlt)-1 and placental growth factor (PIGF) have been implicated in the
      mechanisms of disease responsible for preeclampsia (PE). Moreover, it has been
      proposed that the concentrations of these markers in maternal serum/plasma may
      have predictive value. This study evaluates a newly developed Elecsys (Roche,
      Penzberg, Germany) assay for sFlt-1 and PIGF and tests the value of the sFlt
      1/PIGF ratio in the assessment of PE. STUDY DESIGN: This multicenter case-control
      study included 351 patients: 71 patients with PE and 280 gestational age-matched
      control subjects from 5 European study centers. A total of 595 serum samples were
      measured for sFlt-1 and PIGF using an automated platform. RESULTS: Maternal serum
      concentrations of sFlt-1 and PIGF significantly separated healthy women and women
      with PE. The sFlt-1/PIGF ratio had an area under the receiver operating
      characteristic curve of 0.95. The best performance was obtained in the
      identification of early-onset PE (area under the receiver operating
      characteristic curve of 0.97). CONCLUSION: Measurement of sFlt-1 and PIGF and
      calculation of sFlt-1/PIGF ratio can be performed quickly and in a platform
      available in clinical laboratories. This is a substantial step forward in
      bringing the determination of these analytes to clinical practice in obstetrics.
      We propose that sFlt-1, PIGF, and sFlt-1/PIGF ratio may be of value in the
      prediction of PE and in the differential diagnosis of patients with atypical
      presentations of PE, and perhaps in the differential diagnosis of women with
      chronic hypertension suspected to develop superimposed PE.

PMID- 19850277
TI  - [From the standard coronary angiography to the double rotational angiography:
      results of a retrospective mono-centric registry].
AB  - X-ray doses (delivered) to the patients during coronary angiography (CA) and
      percutaneous coronary intervention (PCI) show ability of one certain deterious
      effects and can be sometimes at very high level. According to the European
      directives, all the equipments allowing to make diagnostic and interventional
      procedure integrate a unit of measure of the Dose Area Product. This measure is
      associated in a linear way with the effective dose and allows to measure the
      stochastic risk, the indicator also of good practices. Stemming from general
      vascular rotational acquisition technology, the cardiac rotational angiography is
      potentially beneficial for the patients and the operators concerning the exposure
      in ionizing radiations. The purpose of this study is to measure retrospectively
      the various dominating indicators in the irradiation of the patients on a series
      of case realized from January, 2009 till May, 2009 further to the implementation
      of this technique of acquisition. The dose area product, the duration of
      fluoroscopy as well as the number of acquired images were measured after coronary
      angiogram at 250 consecutive patients between January, 2009 and May, 2009. The
      procedures were realized by four operators, using the femoral access. The dose
      area product, the durations of fluoroscopy as well as the number of images has
      been respectively of 39,3 Gy cm(2) [4,7-210,65 Gy cm(2)], 8,4 minutes [0,8-38
      minutes] and 575 frames [175-1427 frames] in standard coronary angiogram; 33,64
      Gy cm(2) [4,95-85,6 Gy cm(2)], 2,8 minutes [1,1-26 minutes], 503 frames [314-836
      frames] in single rotational coronary angiogram; 24,26 Gy cm(2) [5,74-51,1 Gy
      cm(2)], 3,9 minutes [1,3-14 minutes], 272 frames [127-429 frames] in double
      rotational coronary angiogram. In conclusion, the exposure of the patient to the
      X-rays, the practitioners and paramedical in interventional cardiology depends on
      the operator, on the fluoroscopy time and on the number of acquired images. The
      double rotational angiography is one of the solution to achieve these objectives.

PMID- 19850278
TI  - [Persistent stapedial artery with otosclerosis].
AB  - OBJECTIVES: A persistent stapedial artery is a rare vascular malformation. This
      diagnosis is based on CT scan and intraoperative findings. MATERIAL AND METHODS:
      The case of a 19-year-old woman with a persistent stapedial artery found during
      stapes surgery is reported. This vascular malformation was explored with a CT
      scan showing the bilaterality of this anatomical variation and signs of
      associated otosclerosis. RESULTS: This malformation was successfully coagulated
      with laser allowing the stapedotomy to be completed. CONCLUSIONS: A persistent
      stapedial artery is not a contraindication to stapedotomy because it can be
      safely coagulated during the same procedure.

PMID- 19850279
TI  - Normalisation of calcium status reverses the phenotype in dentin, but not in
      enamel of VDR-deficient mice.
AB  - OBJECTIVE: To determine the effects of vitamin D receptor (VDR) deficiency on
      mouse dentin and enamel mineralisation, and how normalisation of serum calcium
      level affects dentin and enamel phenotypes in VDR knockout mice. MATERIALS AND
      METHODS: Groups of VDR wild-type (VDR+/+), VDR deficient (VDR-/-) and VDR-/-
      rescued mice were sacrificed at 70.5 days of life. The rescued group was
      established by a high-calcium diet feeding the VDR-/- mice from postnatal 19
      days. Micro-CT was used to compare enamel and dentin mineralisation density (MD)
      at different levels of mandibular incisors among the groups. The scanning
      electron microscope (SEM) was used to examine the ultrastructure of the enamel
      and dentin in the corresponding levels and of surface enamel after acidic
      treatment. RESULTS: Micro-CT showed that in VDR-/- rescued group, dentin
      phenotype was reversed and dentin MD was reversed to normal; however, enamel
      mineralisation was not reversible, and remained as hypermineralisation in molar
      region and apical region of the incisors. SEM also revealed enamel
      hypermineralisation in the VDR-/- rescued group. This early enamel
      hypermineralisation was more susceptible to acidic erosion. CONCLUSION: Vitamin D
      affects dentin mineralisation systemically, and it regulates enamel
      mineralisation locally.

PMID- 19850280
TI  - Effects of smoking on salivary C-telopeptide pyridinoline cross-links of type I
      collagen and osteocalcin levels.
AB  - AIM: This study was planned to investigate whether smoker patients with
      inflammatory periodontal disease exhibit different salivary concentrations of C
      telopeptide pyridinoline cross-links of type I collagen (ICTP) and osteocalcin
      (OC) compared to the non-smoker and/or ex-smoker counterparts. METHODS: Whole
      saliva samples, full-mouth clinical periodontal recordings were obtained from 67
      otherwise healthy patients with inflammatory periodontal disease. According to
      self-reports there were 34 smokers, 22 non-smokers and 11 ex-smokers. Salivary
      cotinine, ICTP and OC levels were determined by enzyme-linked immunoassays.
      RESULTS: Salivary cotinine measurements confirmed self-reports about smoking.
      Smoker patients revealed significantly higher plaque index values than non
      smokers (p<0.05). Bleeding on probing values were significantly lower in smoker
      group than ex-smoker group (p<0.05). There was no significant difference between
      the study groups in salivary ICTP levels (p>0.05). OC levels in smoker group was
      significantly lower than the other groups (p<0.001). Salivary ICTP levels
      correlated negatively with number of teeth present (p<0.05), positively with
      bleeding on probing (p<0.01). Salivary OC levels correlated negatively with years
      smoked (p<0.01). CONCLUSIONS: Within the limits of this study, smoking seems to
      suppress salivary osteocalcin level but ICTP levels seem not to be affected by
      smoking status. This suppression in OC levels may be one mechanism of
      deteriorating effects of smoking on periodontal health.

PMID- 19850281
TI  - Oxytocin: envy or engagement in others?

PMID- 19850284
TI  - Efficient microwave-assisted synthesis of 5-hydroxymethylfurfural from
      concentrated aqueous fructose.
AB  - Studies on the HCl-catalysed microwave-assisted dehydration of highly
      concentrated aqueous fructose (27 wt%) to 5-hydroxymethylfurfural (HMF) revealed
      a significant increase in the fructose conversion rate over the conventional
      heated systems. Water, being the most benign solvent and therefore ideal for
      green and sustainable chemistry, normally is a poor solvent for the dehydration
      process resulting in low HMF selectivities and yields. However, reaction at 200
      degrees C with microwave irradiation with a short reaction time of only 1s
      resulted in good HMF selectivity of 63% and fructose conversion of 52%, while
      prolonged irradiation for 60s (or more) resulted in nearly full fructose
      conversion (95%) but lower HMF yield (53%). Decreasing the fructose concentration
      significantly improved the HMF selectivity, but possibly made the production
      route less attractive from an industrial point of view due to the resultant low
      throughput.

PMID- 19850283
TI  - Identification of novel candidate genes for treatment response to risperidone and
      susceptibility for schizophrenia: integrated analysis among pharmacogenomics,
      mouse expression, and genetic case-control association approaches.
AB  - BACKGROUND: Pharmacogenomic approaches based on genomewide sets of single
      nucleotide polymorphisms (SNPs) are now feasible and offer the potential to
      uncover variants that influence drug response. METHODS: To detect potential
      predictor gene variants for risperidone response in schizophrenic subjects, we
      performed a convergent analysis based on 1) a genomewide (100K SNP) SNP
      pharmacogenetic study of risperidone response and 2) a global transcriptome study
      of genes with mRNA levels influenced by risperidone exposure in mouse prefrontal
      cortex. RESULTS: Fourteen genes were highlighted as of potential relevance to
      risperidone activity in both studies: ATP2B2, HS3ST2, UNC5C, BAG3, PDE7B, PAICS,
      PTGFRN, NR3C2, ZBTB20, ST6GAL2, PIP5K1B, EPHA6, KCNH5, and AJAP1. The SNPs
      related to these genes that were associated in the pharmacogenetic study were
      further assessed for evidence for association with schizophrenia in up to three
      case-control series comprising 1564 cases and 3862 controls in total (Japanese
      [JPN] 1st and 2nd samples and UK sample). Of 14 SNPs tested, one (rs9389370) in
      PDE7B showed significant evidence for association with schizophrenia in a
      discovery sample (p(allele) = .026 in JPN_1st, two-tailed). This finding
      replicated in a joint analysis of two independent case-control samples
      (p(JPN_2nd+UK) = .008, one-tailed, uncorrected) and in all combined data sets
      (p(all) = .0014, two-tailed, uncorrected and p(all) = .018, two-tailed,
      Bonferroni correction). CONCLUSIONS: We identified novel candidate genes for
      treatment response to risperidone and provide evidence that one of these
      additionally may confer susceptibility to schizophrenia. Specifically, PDE7B is
      an attractive candidate gene, although evidence from integrated methodology,
      including pharmacogenomics, pharmacotranscriptomic, and case-control association
      approaches.

PMID- 19850285
TI  - One-pot enzymatic production of beta-D-galactopyranosyl-(1-->3)-2-acetamido-2
      deoxy-D-galactose (galacto-N-biose) from sucrose and 2-acetamido-2-deoxy-D
      galactose (N-acetylgalactosamine).
AB  - Beta-D-Galactopyranosyl-(1-->3)-2-acetamido-2-deoxy-D-galactose (galacto-N-biose,
      GNB) is an important core structure in functional sugar chains such as T-antigen
      disaccharide and the core 1 sugar chain in mucin glycoproteins. We successfully
      developed a one-pot enzymatic production of GNB from sucrose and GalNAc by the
      concomitant action of four enzymes: sucrose phosphorylase, UDP-glucose-hexose 1
      phosphate uridylyltransferase, UDP-glucose 4-epimerase, and galacto-N-biose/lacto
      N-biose I phosphorylase in the presence of UDP-glucose and phosphate, by
      modifying the method of lacto-N-biose I production [Nishimoto, M.; Kitaoka, M.,
      Biosci. Biotechnol. Biochem., 2007, 71, 2101-2104]. The reaction yield of GNB was
      88% from GalNAc. GNB was isolated from the reaction mixture by crystallization
      after yeast treatment to obtain approximately 45 g of GNB in 95% purity from a
      280-mL reaction mixture.

PMID- 19850287
TI  - Presence of 1-->3-linked 2-O-beta-d-xylopyranosyl-alpha-l-arabinofuranosyl side
      chains in cereal arabinoxylans.
AB  - The presence of a fairly uncommon side chain 2-O-beta-D-xylopyranosyl-alpha-L
      arabinofuranosyl in arabinoxylans (AX) from eight different cereal by-products
      was investigated, using (1)H NMR spectroscopy and high-performance anion-exchange
      chromatography with pulsed amperometric detection (HPAEC-PAD) after Shearzyme
      (GH10 endo-1,4-beta-D-xylanase) hydrolysis. This disaccharide side group was
      present in significant amounts in AX extracted from corn cobs and barley husks.
      For the first time, it was also detected in AX from oat spelts and rice husks,
      and in lesser amounts in wheat straw AX. Arabinoxylo-oligosaccharide (AXOS)
      containing the 2-O-beta-D-Xylp-alpha-L-Araf side chain was purified from the oat
      spelt AX hydrolysate and the structure was fully analyzed using 1D and 2D NMR
      spectroscopy. The AXOS was identified as beta-D-Xylp-(1-->2)-alpha-L-Araf-(1-->3)
      beta-D-Xylp-(1-->4)-D-Xyl. To our knowledge, such a structure with 2-O-beta-D
      Xylp-alpha-L-Araf attached to the O-3 of the nonreducing end of xylobiose has not
      been described previously. New information on substitution of AX from various
      cereal by-products was obtained by combining NMR and enzyme-assisted HPAEC-PAD
      analysis.

PMID- 19850286
TI  - Structure of the O-polysaccharides of the lipopolysaccharides of Mesorhizobium
      loti HAMBI 1148 and Mesorhizobium amorphae ATCC 19655 containing two O-methylated
      monosaccharides.
AB  - The O-polysaccharide of Mesorhizobium loti HAMBI 1148 was obtained by mild acid
      degradation of the lipopolysaccharide and studied by sugar and methylation
      analyses, Smith degradation, and (1)H and (13)C NMR spectroscopies, including 2D
      (1)H/(1)H COSY, TOCSY, ROESY, and H-detected (1)H/(13)C HSQC experiments. The O
      polysaccharide was found to have a branched hexasaccharide-repeating unit of the
      following structure: [Formula: see text] where 2-acetamido-2-deoxy-4-O-methyl-D
      glucose (D-GlcNAc4Me) and methyl group on 2-substituted D-rhamnose (Me) shown in
      italics are present in approximately 80% and approximately 40% repeating units,
      respectively. Similar studies of the O-polysaccharide from Mesorhizobium amorphae
      ATCC 19655 by sugar analysis and NMR spectroscopy revealed essentially the same
      structure but a higher content of 3-O-methyl-D-rhamnose ( approximately 70%).

PMID- 19850289
TI  - Anti-human proacrosin antibody inhibits the zona pellucida (ZP)-induced acrosome
      reaction of ZP-bound spermatozoa.
AB  - The anti-acrosin monoclonal antibody AcrC5F10 inhibited proacrosin activation,
      proacrosin-human zona pellucida glycoprotein A (ZPA) binding, and the zona
      pellucida (ZP)-induced acrosome reaction of the ZP-bound spermatozoa but had no
      significant effect on sperm-ZP binding. These results suggest that proacrosin
      acrosin may play an important role in the ZP-induced acrosome reaction of
      spermatozoa after primary binding to the ZP.

PMID- 19850290
TI  - A novel technique of selective uterine devascularization before myomectomy at the
      time of cesarean section: a pilot study.
AB  - Selective uterine devascularization before myomectomy at the time of cesarean
      section is a novel technique that facilitates myomectomy and is a safe procedure
      avoiding the need for subsequent surgery.

PMID- 19850291
TI  - Fracture healing and bone regeneration: autologous bone grafting or BMPs?

PMID- 19850292
TI  - Averting maternal death and disability. Editor's comment.

PMID- 19850293
TI  - The mediating role of psychological empowerment on job satisfaction and
      organizational commitment for school health nurses: a cross-sectional
      questionnaire survey.
AB  - BACKGROUND: The importance of the professional role of school health nurses in
      promoting children's health in their school environment is widely recognized.
      However, studies of their working experience have revealed feelings of
      disempowerment that appear to be related to insufficient support from school
      managers. In these unsupportive working environments, it seems possible that
      psychological empowerment may play a mediating role to strengthen employees'
      satisfaction and commitment to their employing organization. OBJECTIVES: The aim
      of this study is to test an exploratory model of empowerment in a Taiwanese
      sample of school health nurses by examining the mediating role of psychological
      empowerment in the relationship between external factors and work-related
      attitudes, specifically job satisfaction and organizational commitment. DESIGN: A
      cross-sectional survey with self-reported questionnaires. PARTICIPANTS AND
      METHODS: Probability proportional sampling was used to generate a randomly
      selected sample of 500 school health nurses in elementary and junior high schools
      in Taiwan. A total of 330 valid questionnaires were returned, yielding a response
      rate of 66%. RESULTS: The exploratory model including all hypothesized variables
      provided an adequate fit (chi(2)=29.24; df=17; p=.052; adjusted goodness-of-fit
      index [AGFI]=.96; goodness-of-fit index [GFI]=.98; root-mean-square error of
      approximation [RMSEA]=.05) for the data and indicated that psychological
      empowerment did not fully mediate the relationship between organizational
      empowerment and job satisfaction because of the strong direct effects of
      organizational empowerment on job satisfaction. The influence of empowerment on
      organizational commitment was mediated through job satisfaction. CONCLUSIONS:
      Psychological empowerment did not mediate the relationship between external
      factors and work attitudes, and job satisfaction emerged as an important factor.
      If school leaders can improve the job satisfaction of school health nurses, this
      will help them achieve greater commitment and loyalty of school health nurses to
      their employing schools.

PMID- 19850294
TI  - [Takedown of the hepatic flexure for extended left hemicolectomy].

PMID- 19850295
TI  - [Why should an abdominal CT scan be performed for suspected appendicitis in the
      adult patient? Lessons from ten clinical cases].
AB  - Ten years after its introduction, the contribution and indications for computed
      tomography (CT) in the diagnosis of appendicitis remain the subject of
      controversy among surgeons. Many argue that CT is frequently superfluous and
      costly, results in excessive radiation exposure, and delays surgical treatment.
      On our service, we perform 150 to 180 adult appendectomies annually. We feel that
      CT helps us to avoid unnecessary appendectomy, to clear up diagnostic
      uncertainty, and, most importantly, to guide the choice of surgical approach. We
      illustrate our experience through ten clinical cases in which the use of
      preoperative imaging has resulted in improved care.

PMID- 19850296
TI  - Synthesis of hydrophilic boronate affinity monolithic capillary for specific
      capture of glycoproteins by capillary liquid chromatography.
AB  - Boronate affinity chromatography is an important tool for specific isolation of
      cis-diol-containing compounds such as glycoproteins, RNA and carbohydrates.
      Boronate functionalized monolithic capillaries have been recently developed for
      specific capture of cis-diol-containing small biomolecules, but the apparent
      hydrophobicity of the columns prevents them from specific capture of
      glycoproteins. In this paper, a hydrophilic boronate affinity monolithic
      capillary was prepared by in situ free radical polymerization, using 4
      vinylphenylboronic acid (VPBA) and N, N'-methylenebisacrylamide (MBAA) as
      functional monomer and cross-linker, respectively. The prepared poly(VPBA-co
      MBAA) monolithic capillary exhibited uniform open channel network and high
      density of accessible boronic acid. Due to the utilization of hydrophilic cross
      linker, the prepared column was hydrophilic, allowing for specific capture of
      glycoproteins.

PMID- 19850297
TI  - Multiple dual-mode countercurrent chromatography applied to chiral separations
      using a (S)-naproxen derivative as chiral selector.
AB  - Countercurrent chromatography (CCC) is a liquid-liquid chromatographic technique
      without a solid support. Several alternative elution modes can be applied to take
      advantage of the special nature of the liquid stationary phase. Among these dual
      mode (DM) and multiple dual-mode (MDM) consist of switching alternatively between
      Reversed and Normal Phase operation during the experiment (once for DM and
      several times for MDM). In this paper, MDM has been applied to the chiral CCC
      separations of two racemic mixtures, (+/-)-N-(3,4-cis-3-decyl-1,2,3,4
      tetrahydrophenanthren-4-yl)-3,5-dinitrobenzamide and N-(3,5-dinitrobenzoyl)-(+/-)
      leucine, using (S)-naproxen N,N-diethylamide as chiral selector (CS). Although
      the behaviour of the two analytes differed, improved resolution factors were
      successfully obtained. Results are rationalized on the basis of the distinct
      partition behaviour of the CS/enantiomer complexes in the biphasic system.

PMID- 19850298
TI  - Systematic evaluation of new chiral stationary phases for supercritical fluid
      chromatography using a standard racemate library.
AB  - A systematic approach to the evaluation of new chiral stationary phases (CSPs)
      for supercritical fluid chromatography (SFC) using a standard library of racemic
      analytes is described. A standard library of racemic analytes representing a
      variety of functional group classes was assembled from a mixture of proprietary
      and commercial compounds. The library is dispensed and stored in a convenient 96
      well microplate format to facilitate ease of use, and to minimize the amount of
      analyte required for analysis. Automated SFC screening was performed on both
      established CSPs in common use, as well as a group of six recently commercialized
      CSPs. Screening results were archived in a structure-searchable database that
      allows convenient comparison of performance data to determine which CSPs shows
      the best performance.

PMID- 19850299
TI  - Synthesis, characterization of palygorskite supported zero-valent iron and its
      application for methylene blue adsorption.
AB  - In this work, natural palygorskite impregnated with zero-valent iron (ZVI) was
      prepared and characterized. The combination of ZVI particles on surface of
      fibrous palygorskite can help to overcome the disadvantage of ultra-fine powders
      which may have strong tendency to agglomerate into larger particles, resulting in
      an adverse effect on both effective surface area and catalyst performance. There
      is a significant increase of methylene blue (MB) decolourized efficiency on acid
      treated palygorskite with ZVI grafted, within 5 min, the concentration of MB in
      the solution was decreased from 94 mg/L to around 20 mg/L and the equilibration
      was reached at about 30-60 min with only around 10 mg/L MB remained in solution.
      Changes in the surface and structure of prepared materials were characterized
      using X-ray diffraction (XRD), infrared (IR) spectroscopy, surface analysing and
      scanning electron microscopy (SEM) with element analysis and mapping. Comparing
      with zero-valent iron and palygorskite, the presence of zero-valent iron reactive
      species on the palygorskite surface strongly increases the decolourization
      capacity for methylene blue, and it is significant for providing novel modified
      clay catalyst materials for the removal of organic contaminants from waste water.

PMID- 19850300
TI  - Facile synthesis of Fe3O4 nanoparticles by reduction phase transformation from
      gamma-Fe2O3 nanoparticles in organic solvent.
AB  - A phase transformation induced by the reduction of as-synthesized gamma-maghemite
      (gamma-Fe(2)O(3)) nanoparticles was performed in solution by exploiting the
      reservoir of reduction gas (CO) generated from the incomplete combustion reaction
      of organic substances in the reactor. Results from X-ray diffraction, color
      indicator, and magnetic analysis using a SQUID strongly support this phase
      transformation. Based on this route, monodisperse magnetite (Fe(3)O(4))
      nanoparticles were simply produced in the range from 260 to 300 degrees C. Almost
      all aspects of the original gamma-Fe(2)O(3) nanoparticles, such as shape, size,
      and monodispersity, were maintained in the produced Fe(3)O(4) nanoparticles.

PMID- 19850301
TI  - Serum procalcitonin for prediction of renal parenchymal involvement in children
      with urinary tract infections: a meta-analysis of prospective clinical studies.
AB  - OBJECTIVE: To determine by meta-analysis whether serum procalcitonin (PCT) is a
      useful marker of acute renal parenchymal involvement (RPI) in children with
      culture-proven urinary tract infection (UTI), as diagnosed by acute-phase DMSA
      (Tc-99m dimercaptosuccinic acid) renal scintigraphy. STUDY DESIGN: We searched
      PubMed and the Cochrane Central Register of Controlled Trials for prospective
      studies involving children with culture-proven UTIs. Additional eligibility
      criteria were measurement of serum PCT at presentation and performance of DMSA
      scintigraphy within 14 days. RESULTS: Overall, 10 studies eligible for inclusion,
      involving a total of 627 children, were identified. Half of these studies
      evaluated children with a first episode of UTI; 8 involved children with febrile
      UTIs. Using a cutoff value of 0.5 to 0.6 ng/mL, the pooled diagnostic odds ratio
      of serum PCT for UTI with RPI was 14.25 (95% confidence interval, 4.70 to 43.23).
      High statistical between-study heterogeneity that could mainly be attributed to 2
      studies was observed. The remaining 8 studies uniformly favored PCT use.
      CONCLUSIONS: In children with culture-proven UTI, a serum PCT value >0.5 ng/mL
      predicts reasonably well the presence of RPI, as evidenced by DMSA scintigraphy.
      PCT may aid in the identification of children with UTI, necessitating more
      intense evaluation and management.

PMID- 19850302
TI  - Oxidative stress and neopterin abnormalities in schizophrenia: a longitudinal
      study.
AB  - Oxidative stress abnormalities have been proposed to explain the pathogenesis of
      schizophrenia. The present study examined neopterin and oxidative stress
      abnormalities in schizophrenia patients before and after treatment. Serum
      neopterin, total anti-oxidants, nitrites and thiols in antipsychotic-naive
      schizophrenia patients (n=45) were assessed at baseline before treatment in
      comparison with healthy controls (n=43). The schizophrenia patients on treatment
      were followed up for 3months and these parameters were reassessed (n=32). In
      comparison to healthy controls, schizophrenia patients had significantly higher
      levels of neopterin and nitrites and significantly lower levels of anti-oxidants
      before treatment. During follow-up assessments in schizophrenia patients after
      treatment with antipsychotics, there was a significant decrease in the neopterin
      levels and significant increase in anti-oxidant levels. Our study observations
      support increased oxidative stress in schizophrenia that improves with
      antipsychotic treatment.

PMID- 19850303
TI  - The influence of psychiatric comorbidities and sexual trauma on lower urinary
      tract symptoms in female veterans.
AB  - PURPOSE: We characterized the association of psychiatric comorbidities and sexual
      trauma with lower urinary tract symptoms in women. MATERIALS AND METHODS:
      Consecutive women (121) referred for evaluation of lower urinary tract symptoms
      to a specialized urology clinic were given validated questionnaires including the
      Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7. These
      data were then analyzed according to psychiatric comorbidities, history of sexual
      trauma, age, race and obstetric history. Baseline incidence of psychiatric
      comorbidity and sexual trauma was also compared to a control population (1,298)
      from which all patients were referred. RESULTS: Women referred for evaluation of
      lower urinary tract symptoms had higher rates of psychiatric comorbidities (64.5%
      vs 25.9%, p <0.001) and sexual trauma (49.6% vs 20.1%, p <0.001) compared to
      those in the primary care clinic. Total survey scores for the Incontinence Impact
      Questionnaire-7 were significantly higher for patients with psychiatric
      comorbidities and sexual trauma (11.05 +/- 0.84) compared to scores of patients
      with neither of these conditions (7.6 +/- 1.02, p = 0.010). Stepwise multivariate
      regression analyses demonstrated that higher Urogenital Distress Inventory-6
      scores were associated only with age younger than 50 years and history of
      miscarriage, and that higher Incontinence Impact Questionnaire-7 scores were
      associated only with psychiatric comorbidities and history of miscarriage.
      CONCLUSIONS: Psychiatric comorbidities and sexual trauma are prevalent in female
      veterans presenting for evaluation of lower urinary tract symptoms and
      psychiatric comorbidities are associated with greater quality of life impact.

PMID- 19850304
TI  - Organotin compounds in the Paranagua Estuarine Complex, Parana, Brazil:
      evaluation of biological effects, surface sediment, and suspended particulate
      matter.

PMID- 19850305
TI  - [Post-authorisation studies in Spain: legal frame, problems and solutions].

PMID- 19850306
TI  - [Clinical overdoing of consensus conference about hypertension].

PMID- 19850308
TI  - Enhanced neutrophil expression of annexin-1 in coronary artery disease.
AB  - The systemic inflammatory activity in patients with stable coronary artery
      disease (CAD) is associated with a dysregulated cortisol response. Moreover, an
      aberrant activation status of neutrophils in CAD has been discussed; and the
      question of glucocorticoid resistance has been raised. The anti-inflammatory
      actions of glucocorticoids are mediated by annexin-1 (ANXA1). We investigated the
      expression of glucocorticoid receptors (GR) and ANXA1, as well as the exogenous
      effects of ANXA1 on neutrophils in CAD patients and related the data to diurnal
      salivary cortisol. Salivary cortisol levels were measured in the morning and
      evening during 3 consecutive days in 30 CAD patients and 30 healthy individuals.
      The neutrophil expression of GR and ANXA1 was determined by flow cytometry. The
      effect of exogenous ANXA1 was determined in a neutrophil stimulation assay. The
      patients showed a flattened diurnal cortisol pattern compared with healthy
      subjects, involving higher levels in the evening. The neutrophil expression of GR
      total and GR-alpha was decreased, whereas the GR-beta expression did not differ
      compared with controls. The neutrophil expression of ANXA1 was significantly
      increased in patients. Ex vivo, ANXA1 impaired the leukotriene B(4)-induced
      neutrophil production of reactive oxygen species in patients but not in controls.
      Our findings indicate a persistent overactivation of the hypothalamic-pituitary
      adrenal axis in CAD patients but do not give any evidence for glucocorticoid
      resistance, as assessed by the neutrophil expression of GR and ANXA1. The altered
      neutrophil phenotype in CAD may thus represent a long-term response to disease
      related activation.

PMID- 19850309
TI  - Preliminary report: hepatic fat and inflammation in type 2 diabetes mellitus.
AB  - Although the association between inflammation and hepatic fat is fairly
      established, it remains unclear whether this association is independent of
      general measures of obesity and standard cardiovascular risk factors. Therefore,
      the aim of this study was to investigate the contribution of hepatic steatosis as
      an independent predictor of chronic inflammation in 281 subjects with type 2
      diabetes mellitus. Reduced hepatic steatosis significantly (P < .01) correlated
      with C-reactive protein (r = -0.16) and adiponectin (r = 0.23). The association
      of hepatic steatosis with both C-reactive protein and adiponectin remained
      significant after adjustment for age, ethnicity, body mass index (or waist
      circumference), triglycerides, high-density lipoprotein, and total cholesterol.
      These data support the concept that accumulation of hepatic fat is related to
      enhanced inflammation in type 2 diabetes mellitus independent of general measures
      of obesity and standard cardiovascular risk factors.

PMID- 19850310
TI  - Dysregulation of glucose, insulin, triglyceride, blood pressure, and oxidative
      stress after an oral glucose tolerance test in men with abdominal obesity.
AB  - Postprandial metabolic dysregulation plays a role in the development of
      atherosclerosis. Visceral fat accumulation is an important component of various
      metabolic disorders including glucose intolerance, dyslipidemia, and
      hypertension, which correlate with atherosclerotic cardiovascular disease. The
      aim of the present study was to compare the postprandial response of various
      metabolic parameters, blood pressure, adiponectin, and oxidative stress to 75-g
      oral glucose tolerance test (OGTT) in men with (n = 23) and without (n = 7)
      abdominal obesity based on waist circumference (WC) cutoff value of 85 cm (based
      on the Japanese criteria for the metabolic syndrome). The cross-sectional
      prospective study included 30 male subjects who were on no medications and newly
      diagnosed with mild hypertension and/or dyslipidemia. The percentage change in
      each parameter ([each parameter at 120 minutes after an OGTT - that before an
      OGTT]/that before an OGTT x 100) was calculated. The percentage systolic blood
      pressure, percentage diastolic blood pressure, and percentage triglyceride were 
      6.3% +/- 3.5%, -9.4% +/- 3.0%, and -10.2% +/- 2.1%, respectively, in the WC less
      than 85 group (vs baseline: P = .10, P < .01, and P < .001) and 2.0% +/- 1.7%,
      0.9% +/- 2.4%, and 2.8% +/- 3.3%, respectively, in the WC at least 85 group (vs
      WC <85 group: P < .05, each). However, there were no significant differences in
      percentage total cholesterol and percentage high-density lipoprotein cholesterol
      between the 2 groups. The percentage thiobarbituric acid-reacting substances
      tended to be lower in the WC less than 85 group (vs baseline: P = .07), but not
      in the WC at least 85 group, albeit statistically insignificant (WC <85 vs >/=85
      group: P = .057). The maximum carotid intima-media thickness was larger in the WC
      at least 85 group than the WC less than 85 group (P < .05). Evaluation of
      postprandial changes in obesity-related parameters may be important in preventing
      atherosclerotic diseases.

PMID- 19850311
TI  - Prime-boost immunization with HA/C3d DNA followed by a recombinant pseudorabies
      virus boost enhanced protective immunity against H3N2 swine influenza virus in
      mice.
AB  - DNA and recombinant virus vaccines against swine influenza virus (SIV) have been
      pursued with promising results, but induce poor immunogenicity. This study
      evaluated the effects of a vaccine regimen in mice including priming with three
      DNA vaccines expressing soluble HA (sHA), complete HA (tmHA), or sHA fused with
      three copies murine C3d (sHA-mC3d3) and boosting with recombinant pseudorabies
      virus expressing HA (rPRV-HA). Immune responses were monitored by ELISA, HI
      assays, and virus neutralization. Protective efficacy was evaluated by virus
      isolation from lungs, distribution in tissues, and pathology following challenge
      with H3N2 SIV. Priming with sHA-mC3d3 and boosting with rPRV-HA induced higher
      levels of HA-specific antibodies and yielded the most effective protection. This
      finding implied that priming with a DNA vaccine expressing C3d fused with antigen
      and boosting with a recombinant vector vaccine is an effective way to induce
      protective humoral immunity and prevent some infectious diseases.

PMID- 19850312
TI  - Surface acoustic waves in interaction with a dislocation.
AB  - A surface acoustic wave can interact with dislocations that are close to the
      surface. We characterize this interaction and its manifestations as scattered
      surface acoustic waves for different orientations with respect to the surface of
      an edge dislocation. For dislocations that are parallel or perpendicular to the
      free surface, we present an analytical result for short dislocations with respect
      to the wave-length that reproduce qualitatively the main features observed for
      dislocations of various sizes.

PMID- 19850313
TI  - Generalized eigenproblem of hybrid matrix for Floquet wave propagation in one
      dimensional phononic crystals with solids and fluids.
AB  - A method based on the solution to a generalized eigenproblem of hybrid matrix is
      presented for stable analysis of Floquet wave propagation in one-dimensional
      phononic crystals with solids and fluids. The method overcomes the numerical
      instability in the standard eigenproblem of transfer matrix, thus enabling
      Floquet waves to be determined reliably. The recursion relations of hybrid matrix
      for periodic multilayered structure of various solid and/or fluid phases are
      formulated. Dispersion relation and omnidirectional reflection for one
      dimensional phononic crystals with solids and fluids are discussed. The frequency
      thickness range of phononic bandgap is determined conveniently based on the
      Floquet wavenumbers.

PMID- 19850314
TI  - Electric field effects in RUS measurements.
AB  - Much of the power of the Resonant Ultrasound Spectroscopy (RUS) technique is the
      ability to make mechanical resonance measurements while the environment of the
      sample is changed. Temperature and magnetic field are important examples. Due to
      the common use of piezoelectric transducers near the sample, applied electric
      fields introduce complications, but many materials have technologically
      interesting responses to applied static and RF electric fields. Non-contact
      optical, buffered, or shielded transducers permit the application of charge and
      externally applied electric fields while making RUS measurements. For conducting
      samples, in vacuum, charging produces a small negative pressure in the volume of
      the material--a state rarely explored. At very high charges we influence the
      electron density near the surface so the propagation of surface waves and their
      resonances may give us a handle on the relationship of electron density to bond
      strength and elasticity. Our preliminary results indicate a charge sign dependent
      effect, but we are studying a number of possible other effects induced by
      charging. In dielectric materials, external electric fields influence the strain
      response, particularly in ferroelectrics. Experiments to study this connection at
      phase transformations are planned. The fact that many geological samples contain
      single crystal quartz suggests a possible use of the piezoelectric response to
      drive vibrations using applied RF fields. In polycrystals, averaging of strains
      in randomly oriented crystals implies using the "statistical residual" strain as
      the drive. The ability to excite vibrations in quartzite polycrystals and
      arenites is explored. We present results of experimental and theoretical
      approaches to electric field effects using RUS methods.

PMID- 19850315
TI  - Enhanced intracellular retention of a hepatitis B virus strain associated with
      fulminant hepatitis.
AB  - A plasmid carrying 1.3-fold HBV genome was constructed from a HBV strain that
      caused five consecutive cases of fulminant hepatitis (pBFH2), and HepG2 cells
      were transfected with pBFH2 or its variants. The pBFH2 construct with
      A1762T/G1764A, G1862T, and G1896A showed the largest amount of core particle
      associated intracellular HBV DNA, but no significant increase of extracellular
      HBV DNA in comparison with the wild construct, suggesting that these mutations
      might work together for retention of the replicative intermediates in the cells.
      The retention might relate to the localization of hepatitis B core antigen
      (HBcAg) in the nucleus of HepG2, which was observed by confocal fluorescence
      microscopy. HBcAg immunohistochemical examination of liver tissue samples
      obtained from the consecutive fulminant hepatitis patients showed stronger
      staining in the nucleus than acute hepatitis patients. In conclusion, the
      fulminant HBV strain caused retention of the core particles and the core particle
      associated HBV DNA in the cells.

PMID- 19850316
TI  - Ammonium nitrogen removal from coking wastewater by chemical precipitation
      recycle technology.
AB  - Ammonium nitrogen removal from wastewater has been of considerable concern for
      several decades. In the present research, we examined chemical precipitation
      recycle technology (CPRT) for ammonium nitrogen removal from coking wastewater.
      The pyrolysate resulting from magnesium ammonium phosphate (MAP) pyrogenation in
      sodium hydroxide (NaOH) solution was recycled for ammonium nitrogen removal from
      coking wastewater. The objective of this study was to investigate the conditions
      for MAP pyrogenation and to characterize of MAP pyrolysate for its feasibility in
      recycling. Furthermore, MAP pyrolysate was characterized by scanning electron
      microscope (FESEM), transmission electron microscope (TEM), Fourier transform
      infrared spectroscopy (FTIR) as well as X-ray diffraction (XRD). The MAP
      pyrolysate could be produced at the optimal condition of a hydroxyl (OH(-)) to
      ammonium molar ratio of 2:1, a heating temperature of 110 degrees C, and a
      heating time of 3h. Surface characterization analysis indicated that the main
      component of the pyrolysate was amorphous magnesium sodium phosphate (MgNaPO(4)).
      The pyrolysate could be recycled as a magnesium and phosphate source at an
      optimum pH of 9.5. When the recycle times were increased, the ammonium nitrogen
      removal ratio gradually decreased if the pyrolysate was used without
      supplementation. When the recycle times were increased, the ammonium nitrogen
      removal efficiency was not decreased if the added pyrolysate was supplemented
      with MgCl(2).6H(2)O plus Na(2)HPO(4).12H(2)O during treatment. A high ammonium
      nitrogen removal ratio was obtained by using pre-formed MAP as seeding material.

PMID- 19850317
TI  - Oxidation of atenolol, propranolol, carbamazepine and clofibric acid by a
      biological Fenton-like system mediated by the white-rot fungus Trametes
      versicolor.
AB  - Biological advanced oxidation of the pharmaceuticals clofibric acid (CA),
      carbamazepine (CBZP), atenolol (ATL) and propranolol (PPL) is reported for the
      first time. Extracellular oxidizing species were produced through a quinone redox
      cycling mechanism catalyzed by an intracellular quinone reductase and any of the
      ligninolytic enzymes of Trametes versicolor after addition of the lignin-derived
      quinone 2,6-dimethoxy-1,4-benzoquinone (DBQ) and Fe(3+)-oxalate in the medium.
      Time-course experiments with approximately 10mg L(-1) of initial pharmaceutical
      concentration resulted in percent degradations above 80% after 6h of incubation.
      Oxidation of pharmaceuticals was only observed under DBQ redox cycling
      conditions. A similar degradation pattern was observed when CBZP was added at the
      environmentally relevant concentration of 50 microg L(-1). Depletion of DBQ due
      to the attack of oxidizing agents was assumed to be the main limiting factor of
      pharmaceutical degradation. The main degradation products, that resulted to be
      pharmaceutical hydroxylated derivatives, were structurally elucidated. The
      detected 4- and 7-hydroxycarbamazepine intermediates of CBZP degradation were not
      reported to date. Total disappearance of intermediates was observed in all the
      experiments at the end of the incubation period.

PMID- 19850318
TI  - The use of Collembola avoidance tests to characterize sewage sludges as soil
      amendments.
AB  - The ecotoxicological characterization of sewage sludge takes into account the
      additive, antagonistic and synergistic effects that occur as a result of multi
      chemical interactions. Such an evaluation therefore is essential to complement
      the chemical analysis that, although required by law, is clearly insufficient.
      Using a tiered approach in the toxic evaluation of sewage sludge allows for
      characterization of toxicity in a timely manner. According to the literature,
      reproduction tests with Folsomia candida are suitable tools for the toxic
      assessment of organic sludges. Therefore, the inclusion of Collembola avoidance
      tests at a screening level (low tier), and acting as a trigger for longer-period
      tests (high tier; e.g. reproduction test), may provide a successful strategy, and
      may complement the currently proposed test battery. To evaluate the use of both
      avoidance and reproduction tests with collembolans in such a tiered approach,
      three sewage sludges (urban, olive and electroplating industries) were mixed in
      with a field-collected soil at different concentrations. Avoidance and
      reproduction tests were performed with the soil-sludge mixtures after 0, 4 and 12
      weeks of incubation. The tests detected no toxicity in soil-sludge mixtures of
      urban and olive sludges at any incubation period. Mixtures with sludge from the
      electroplating industry induced toxicity only in the avoidance tests with freshly
      prepared and 4-week incubated samples. These results demonstrate the ability of
      Collembola avoidance tests to assess sewage sludge toxicity over time and its
      potential for hazardous sludge characterization at low tier levels.

PMID- 19850319
TI  - Relationship between the concentrations of polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans, and polychlorinated biphenyls in maternal blood
      and those in breast milk.
AB  - We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls
      (PCBs), and non-dioxin-like PCBs in paired samples of blood and breast milk
      collected from 89 primiparous mothers in Sapporo City, Japan, and studied the
      relationships of these compounds between blood and breast milk for these women
      plus 30 primiparous mothers in whom these data had been previously reported. The
      present study is one of the few studies in which the concentration distributions
      of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs have been
      investigated in blood and breast milk collected from the same mothers. The
      arithmetic mean TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono
      ortho PCBs in blood and breast milk of these 119 subjects were 8.2, 2.9, 5.1, and
      0.4 pg TEQ g(-1)lipid, respectively, and 4.8, 2.0, 4.0, and 0.4 pg TEQ g(
      1)lipid, respectively, with the total TEQ concentrations of these dioxin-like
      compounds being 7.0-36 (mean: 17, median: 14) and 5.7-41 (mean: 11, median: 10)
      pg TEQ g(-1)lipid, respectively. The sums of the concentrations of 56 non-dioxin
      like PCB congeners that were measured in the subjects' blood and breast milk were
      43-445 (mean: 120, median: 106) and 34-366 (mean: 90, median: 81) ng g(-1)lipid,
      respectively, indicating that the total TEQ concentration and the total
      concentration of 56 non-dioxin-like PCB congeners in the maternal blood were
      notably higher than those in the breast milk. Statistically significant
      correlations were observed between maternal age and the total TEQ concentration
      of PCDDs, PCDFs, and dioxin-like PCBs or the total concentration of 56 non-dioxin
      like PCB congeners in maternal blood, and significant correlations were also
      observed between maternal age and the total TEQ concentration of these dioxin
      like compounds or the total concentration of 56 PCB congeners in breast milk. The
      total TEQ concentration of PCDDs, PCDFs, and dioxin-like PCBs in maternal blood
      showed a close correlation to that in subjects' breast milk, and there was also
      good correlation between the total concentration of 56 non-dioxin-like PCB
      congeners in maternal blood and that in subjects' breast milk. Pearson and
      Spearman correlation analyses showed a relationship between the total TEQ
      concentration of PCDDs, PCDFs, and dioxin-like PCBs and the total concentration
      of 56 non-dioxin-like PCB congeners in maternal blood, and also showed an
      association between the total TEQ concentration of these dioxin-like compounds
      and the total concentration of 56 PCB congeners in breast milk. The concentration
      of hexaCB-153 in maternal blood showed significant correlations to the total TEQ
      concentration of PCDDs, PCDFs, and dioxin-like PCBs or the total concentration of
      56 non-dioxin-like PCBs in that sample. Moreover, the concentration of hexaCB-153
      in breast milk also showed significant correlations to the total TEQ
      concentration of these dioxin-like compounds or the total concentration of 56 PCB
      congeners in that sample. These findings suggested that hexaCB-153 may be an
      indicator of total TEQ concentrations of PCDDs, PCDFs, and dioxin-like PCBs and
      total concentrations of 56 non-dioxin-like PCB congeners in blood and breast milk
      of primiparous mothers.

PMID- 19850320
TI  - Leaching potential of arsenic from Pteris vittata L. under field conditions.
AB  - Foliar leaching might be an important process in the biogeochemical cycle of
      elements, but the leaching behaviors of As remain unclear. This study examined As
      leaching from foliage of an As-hyperaccumulator, Pteris vittata L. in the field.
      Results indicated that substantial amounts of As can be leached from the foliage
      by precipitation. Arsenic concentrations in the foliar leachate ranged from 4.06
      to 519 microgL(-1), and the percentages of As(III) with respect to total As in
      leachate ranged from 5% to 10%. A positive linear relationship existed between As
      concentrations of the foliar leachate and the amounts of As accumulated in the
      plant. The rate of As leaching from the leaves was accelerated by an increase of
      rainfall and time in a simulated precipitation experiment. Water-soluble As
      distributed within the cuticle and apoplast of the plant was speculated as the
      main source of the leached As. The As leaching is an important process of within
      ecosystem As cycling in phytoremediation and it deserves further investigation.

PMID- 19850321
TI  - Is low-level environmental mercury exposure of concern to human health?
AB  - Mercury has long been recognised as toxic, principally in relation to its effects
      on humans following acute or prolonged high-level occupational exposures and, in
      the latter half of the last century, from a number of environmental incidents.
      Recognised target organs are the kidneys, central nervous system and thyroid
      glands. Recently concern has grown about the potential risks to the human
      population from current background environmental levels, leading bodies such as
      the World Health Organisation to call for the reduction or, wherever possible,
      elimination of the use of mercury. This review considers the strength of the
      epidemiological evidence on the effects of prolonged low-level exposure to the
      various forms of mercury. The limited research base suggests that several of the
      potential targets of long-term environmental exposure to mercury are similar to
      those occurring from occupational exposure including the renal, cardiovascular
      and immune systems. However, the evidence also suggests that, particularly in the
      case of organic mercury compounds, the most sensitive endpoint is central nervous
      system toxicity, especially in relation to exposure during the in utero period
      and childhood. It also appears that those human populations which have
      traditionally consumed diets high in seafoods are at greatest risk. While the
      extent of risk to the general population that may arise from existing
      environmental exposure levels appears limited, this conclusion is based on an
      incomplete dataset and therefore the general consensus view that exposure to
      mercury in its various forms should be minimised where practical, appears to be
      justified. A number of potential areas of further research are suggested as being
      pre-requisite to the development of a more rigorous risk assessment.

PMID- 19850322
TI  - Generic Assessment Criteria for human health risk assessment of potentially
      contaminated land in China.
AB  - Generic Assessment Criteria (GAC) are derived using widely applicable assumptions
      about the characteristics and behaviour of contaminant sources, pathways and
      receptors. GAC provide nationally consistent guidance, thereby saving money and
      time. Currently, there are no human health based Generic Assessment Criteria
      (GAC) for contaminated sites in China. Protection of human health is therefore
      difficult to ensure and demonstrate; and the lack of GAC makes it difficult to
      tell if there is potential significant risk to human health unless site-specific
      criteria are derived. This paper derived Chinese GAC (GAC) for five inorganic and
      eight organic substances for three regions in China for three land uses: urban
      residential without plant uptake, Chinese cultivated land, and
      commercial/industrial using the SNIFFER model. The SNIFFER model has been further
      implemented with a dermal absorption algorithm and the model default input values
      have been changed to reflect the Chinese exposure scenarios. It is envisaged that
      the modified SNIFFER model could be used to derive GAC for more contaminants,
      more Regions, and more land uses. Further research to enhance the reliability and
      acceptability of the GAC is needed in regional/national surveys in diet and
      working patterns.

PMID- 19850323
TI  - Size distribution of methylmercury associated with particulate and dissolved
      organic matter in freshwaters.
AB  - Water samples were collected from 20 wetland, river and lake sites across Eastern
      Ontario and Western Quebec to investigate the distribution of methylmercury
      (MeHg) associated with various size fractions of dissolved organic matter (DOM).
      Tangential Flow UltraFiltration (TUF) was used to fractionate DOM by nominal
      molecular size (<0.2 microm, <300 kDa, <30 kDa, <5 kDa and <1 kDa). DOM
      fluorescence (DOM FL) and absorbance (DOC Abs) were used to quantify DOM
      photoreactivity and aromaticity in each sample. Significant differences in the
      size-associated distribution of MeHg, Dissolved Organic Carbon (DOC), DOM FL, and
      DOM Abs were observed between wetlands, rivers, and lakes. The low molecular
      weight (LMW) fraction (<5 kDa) in wetlands contained the majority of MeHg (70.0+/
      13.8%), DOC (56.1+/-9.4%), and DOM FL (77.4+/-7.5%). DOM FL was also high in the
      LMW fraction for rivers (60.6+/-25%) and lakes (75.2+/-16.9%). Mean MeHg
      concentrations in the LMW fraction of lakes (41+/-26 pg L(-1)) and rivers (32+/
      19 pg L(-1)) were substantial but much lower than wetlands. Rivers had the
      highest percentage of methylmercury (38.0+/-23.5%) in the particulate (>0.2
      microm) fraction. This research highlights the importance of low molecular weight
      dissolved organic matter in methylmercury fate. For example, a large proportion
      of MeHg was found in the LMW weight fractions (mean=47.3+/-25.4%) of the
      wetlands, rivers, and lakes in this study.

PMID- 19850324
TI  - A review of DEB theory in assessing toxic effects of mixtures.
AB  - In this manuscript we review the use of mechanistic models to interpret effects
      of mixtures of compounds within the framework of the Dynamic Energy Budget (DEB)
      theory. Within this approach the effect of a mixture is built up from the effects
      of the individual components making up the mixture. Understanding effects of
      mixtures is essential as it is impossible to assess effects of all possible
      mixtures experimentally. In contrast to the more classical way of interpreting
      effects of mixtures with concentration addition or effect addition models, DEB
      theory offers a single consistent framework to understand effects of mixtures on
      growth, reproduction and survival in an integrated, way. It systematically
      incorporates exposure time and biology of the organisms, including the natural
      links between the processes of feeding, maintenance, growth, development and
      reproduction. We also give directions for an experimental setup to interpret the
      results within the DEB framework. The DEB framework was successfully applied to
      assess effects of complex mixtures on survival and binary mixtures on sub-lethal
      endpoints. It gives the possibility to explain observed interactions by the
      underlying biological mechanisms or pinpoint interactions. We expect this
      approach to help in identifying key mechanisms and enable to focus further
      research in cooperation with modelers and experimentalists to improve our
      understanding of the mechanisms underlying mixture toxicity.

PMID- 19850325
TI  - Determinants of atmospheric mercury concentrations in Reno, Nevada, U.S.A.
AB  - Concentrations of gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM)
      and particulate-bound mercury (PBM) were measured along with ancillary variables
      9 km east of downtown Reno, Nevada, U.S.A. from November 2006 through March 2009.
      Mean two-year (February 2007 through January 2009) GEM, GOM, and PBM
      concentrations were 2.0+/-0.7 ng m(-3) (+/-standard deviation), 18+/-22 pg m(-3),
      and 7+/-7 pg m(-3), respectively. Data collected were compared with observations
      made at another location just north of the city at 169 m higher elevation. At
      both locations higher concentrations of GEM and PBM occurred in periods with
      little atmospheric mixing, indicating that local sources were important for
      enhancing GEM and PBM concentrations in Reno above that considered continental
      background. Concentrations of GOM were higher (maximum of 177 pg m(-3)) during
      periods with higher temperature and lower dew point. Higher GOM concentrations at
      the higher elevation site with less urban impact relative to the valley site,
      along with other data trends, support the hypothesis that in northern Nevada
      subsiding dry air from the free troposphere is a source of GOM to the surface.

PMID- 19850326
TI  - Homocysteine decreases extracellular nucleotide hydrolysis in rat platelets.
AB  - Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease.
      Platelets play an important role in cardiovascular disease and release pro
      aggregates mediators when activated, such as ADP, a physiological agonist
      involved in normal hemostasis and thrombosis. NTPDases and 5'-nucleotidase are
      ecto-enzymes that hydrolyze ATP, ADP and AMP to adenosine playing an important
      role on blood flow and thrombogenesis by regulating ADP catabolism. The aim of
      the present study was evaluate extracellular adenine nucleotide hydrolysis of rat
      platelets exposed to homocysteine in vitro and in vivo. In vitro homocysteine
      (Hcy) in the concentration range of 20 to 500 microM caused a significant
      decrease on ATP (around 30%) and ADP (around 45%) hydrolysis, respectively, while
      AMP hydrolysis was not altered. Hcy was not able to inhibit the hydrolysis of ATP
      and ADP catalyzed by purified apyrase at the same concentrations tested in vitro
      on platelets, suggesting an indirect effect. The inhibitory effect of Hcy on
      platelets was prevented by antioxidants agents in vitro and in vivo. Furthermore
      homocysteine treatment increased platelet aggregation induced by ADP. Based on
      the results presented herein, we propose that inhibition of extracellular ATP and
      ADP hydrolysis caused by homocysteine was probably due oxidative stress, since
      antioxidants prevented such effects. These findings may contribute to an increase
      platelet response to ADP and consequence development of thrombotic risk
      attributed to hyperhomocysteinemia.

PMID- 19850327
TI  - Why do we want to know how factor XII levels are modulated?

PMID- 19850328
TI  - Demonstration of substances of innate immunity in the esophageal epithelium of
      domesticated mammals. Part I--Methods and evaluation of comparative fixation.
AB  - The aim of the investigation was to demonstrate that the esophageal epithelium of
      domesticated mammals exhibits characteristic features of innate immunity. The
      esophageal samples used were obtained immediately after euthanization from seven
      species of domesticated mammals of three nutrition groups (herbivores: horse,
      goat, cattle; omnivores: pig, dog, laboratory rat; carnivores: cat). The
      experimental basis was immunohistochemistry, which was evaluated in a qualitative
      and statistically relevant semi-quantitative manner. The first part of the study
      analyzed the influence of different fixation media on the immunohistochemical
      reactivities. Two formalin-based routine fixation solutions (Bouin's solution, Ca
      acetate formalin) were compared with the recently introduced formalin-free
      HOPE(r) fixative. In this context, we clearly demonstrated a diminished
      immunoreactivity for Ca-formol fixed samples; satisfactory results were obtained,
      particularly, from samples fixed in Bouin's solution. The HOPE(r) fixation method
      offers a relatively cheap alternative, as the antibody amounts can be reduced. An
      application in routine diagnostic is not advisable, because of several variable
      parameters. It can be concluded that immunohistochemical results have always to
      be evaluated and discussed in close relation to the fixation medium used.

PMID- 19850330
TI  - Clinical evaluation and follow-up outcome of presurgical plan by Dextroscope: a
      prospective controlled study in patients with skull base tumors.
AB  - BACKGROUND: Patient-specific approach design, comprehensive evaluation on
      perioperative data, and follow-up of postoperative life quality (KPS) were
      carried out to evaluate the application of VR technology of Dextroscope in
      procedures of patients with skull base tumors. METHODS: Eighty-four patients with
      skull base tumors involved in this research were randomized into 2 groups (test
      group and control group), each with 42 patients. Before operation, image data
      such as MR, MRA, or CTA of head were collected and imported into the Dextroscope
      workstation. The detailed preoperative plans were made in the test group, but no
      Dextroscope plans in control group. The resection rate of tumors, preoperative
      evaluation including the duration of operation, total blood loss, the
      postoperative LOS, the number of cases with cerebrovascular injury complications
      in operation, and postoperative KPS of patients on discharge and the sixth month
      follow-up in the 2 groups were recorded and compared. RESULTS: The total
      resection rate of tumors was 83.33% in test group and 71.42% in the control group
      (P > .05). The total resection rate of meningioma was 86.67% in test group and
      76.47% in control group. The total resection rates of trigeminal Schwannoma in
      the 2 groups were all 100% (P > .05). The duration of operation and the
      postoperative LOS of each patient were 5.25 +/- 0.64 hours and 8.50 +/- 1.10 days
      in the test group and 7.36 +/- 0.87 hours and 12.50 +/- 1.52 days in the control
      group, respectively (P < .05). Total blood loss of each patient was 456.75 +/-
      55.76 mL in the test group and 523.85 +/- 66.78 mL in the control group (P > 05).
      There were 3 cases with complications of cerebral vessels injury in the test
      group and 7 cases in the control group (P < .05). During follow-up, KPS of
      patients in the test group on discharge (85.75 +/- 9.68) was significantly
      superior to that in the control group (81.66 +/- 9.24; P < .05). The KPS of
      patients on the sixth-month follow-up in the test group was 92.35 +/- 9.95, which
      was significantly superior to that in the control group (85.6 +/- 9.34; P < .05).
      Karnofsky performance scores of patients in the test group improved significantly
      from discharge to the sixth month after procedure (P < .05), whereas there were
      adverse results in the test group (P < .05). The 2 cases with CSF leakage were
      cured completely. CONCLUSION: The preoperative plans with VR technology in
      patients with skull base tumor or CSF leakage operations can help certain the
      diagnosis, individually locate the position of skull base lesions, and design
      patient-specific approach, which also facilitate to shorten operation duration
      and the postoperative LOS, reduce total blood loss and injury of vessels in
      operation, and improve the postoperative KPS.

PMID- 19850333
TI  - Tissue-specific gene delivery via nanoparticle coating.
AB  - The use of biomaterials for gene delivery can potentially avoid many of the
      safety concerns with viral gene delivery. However, the efficacy of polymeric gene
      delivery methods is low, particularly in vivo. One significant concern is that
      the interior and exterior composition of polymeric gene delivery nanoparticles
      are often coupled, with a single polymer backbone governing all functions from
      biophysical properties of the polymer/DNA particle to DNA condensation and
      release. In this work we develop electrostatically adsorbed poly(glutamic acid)
      based peptide coatings to alter the exterior composition of a core gene delivery
      particle and thereby affect tissue-specificity of gene delivery function in vivo.
      We find that with all coating formulations tested, the coatings reduce potential
      toxicity associated with uncoated cationic gene delivery nanoparticles following
      systemic injection. Particles coated with a low 2.5:1 peptide:DNA weight ratio
      (w/w) form large 2 micro sized particles in the presence of serum that can
      facilitate specific gene delivery to the liver. The same particles coated at a
      higher 20:1w/w form small 200nm particles in the presence of serum that can
      facilitate specific gene delivery to the spleen and bone marrow. Thus, variations
      in nanoparticle peptide coating density can alter the tissue-specificity of gene
      delivery in vivo.

PMID- 19850334
TI  - The relationship between platelet adhesion on surfaces and the structure versus
      the amount of adsorbed fibrinogen.
AB  - While platelet adhesion to biomaterial surfaces is widely recognized to be
      related to adsorbed fibrinogen (Fg), it has remained controversial whether
      platelet adhesion is in response to the adsorbed amount or the adsorbed
      conformation of this protein. To address this issue, we designed a series of
      platelet adhesion studies to clearly separate these two factors, thus enabling us
      to definitively determine whether it is the amount or the conformation of
      adsorbed Fg that mediates platelet response. Fg was adsorbed to a broad range of
      surface chemistries from a wide range of solution concentrations, with the amount
      and conformation of adsorbed Fg determined by absorbance and circular dichroism
      (CD) spectropolarimetry, respectively. Platelet adhesion response was determined
      by lactate dehydrogenase (LDH) assay and scanning electron microscopy (SEM). Our
      results show that platelet adhesion is strongly correlated with the degree of
      adsorption-induced unfolding of Fg (r(2)=0.96) with essentially no correlation
      with the amount of Fg adsorbed (r(2)=0.04). Platelet receptor inhibitor studies
      using an RGDS peptide reduced platelet adhesion by only about 50%, and SEM
      results show that adherent platelets after RGDS blocking were much more rounded
      with minimal extended filopodia compared with the unblocked platelets. These
      results provide definitive proof that the conformation of adsorbed Fg is the
      critical determinant of platelet adhesion, not the amount of Fg adsorbed, with
      adsorption-induced unfolding potentially exposing two distinctly different types
      of platelet binding sites in Fg; one that induces platelet adhesion alone and one
      that induces both platelet adhesion and activation.

PMID- 19850335
TI  - pH-Sensitive fusogenic polymer-modified liposomes as a carrier of antigenic
      proteins for activation of cellular immunity.
AB  - By modification of liposomes with poly(glycidol) derivatives such as succinylated
      poly(glycidol) and 3-methylglutarylated poly(glycidol), we have developed
      functional liposomes that generate fusion ability at mildly acidic pH. We
      investigated the feasibility of these polymer-modified liposomes as a carrier of
      antigenic proteins for induction of cellular immunity. These pH-sensitive
      fusogenic liposomes encapsulating ovalbumin (OVA) were applied to DC2.4 cells, a
      murine dendritic cell line. Observation with confocal laser scanning microscopy
      showed that these polymer-modified liposomes were taken up efficiently by the
      cells, thereafter delivering their contents into the cytosol, probably through
      fusion with endosomal membranes. Murine bone marrow-derived dendritic cells
      treated with polymer-modified liposomes encapsulating OVA stimulated CD8-OVA1.3
      cells more strongly than OT4H.1D5 cells, indicating that the liposomes induced
      MHC class I-restricted presentation. Furthermore, administration of the polymer
      modified, OVA-loaded liposomes from nasal cavities of mice induced stronger
      cellular immune responses than the OVA-loaded plain liposomes. Because the
      ability of the polymer-modified liposomes to activate cellular immunity was
      comparable to that of Freund's complete adjuvant, which is a widely used
      adjuvant, they potentially have use in production of efficient vaccines for
      immunotherapy.

PMID- 19850336
TI  - Enhancement of incisional wound healing by thrombin conjugated iron oxide
      nanoparticles.
AB  - Thrombin has been clinically used for topical hemostasis and wound management for
      more than six decades. The half-life of thrombin in human plasma is shorter than
      15s due to close control by inhibitors. In order to stabilize the thrombin, it
      was bound to maghemite (gamma-Fe(2)O(3)) nanoparticles, as demonstrated in
      previous work. The aim of the present study was to examine the efficiency of the
      bound thrombin for wound healing applications compared to the free thrombin. For
      this purpose incisional wounds on rat skin were treated with a mixture of
      fibrinogen, CaCl(2) solution and free or bound thrombin. The wounds' edges were
      then approximated by skin staples. The control incisional wounds were closed with
      staples only. In the course of 28 days of healing the highest values of skin
      tensile strength were observed following treatment with the bound thrombin.
      Significantly lower values of tensile strength were observed following treatment
      with the free thrombin, and the lowest values were obtained following treatment
      with staples only. The histological findings correlate with the mechanical
      strength measurements, which demonstrate the most advanced stages of healing
      following treatment with the bound thrombin.

PMID- 19850337
TI  - Fatigue and human umbilical cord stem cell seeding characteristics of calcium
      phosphate-chitosan-biodegradable fiber scaffolds.
AB  - Calcium phosphate cement (CPC) has in situ-setting ability and bioactivity, but
      the brittleness and low strength limit CPC to only non-load-bearing bone repairs.
      Human umbilical cord mesenchymal stem cells (hUCMSCs) can be harvested without an
      invasive procedure required for the commonly studied bone marrow MSCs. However,
      little has been reported on hUCMSC delivery via bioactive scaffolds for bone
      tissue engineering. The objectives of this study were to develop CPC scaffolds
      with improved resistance to fatigue and fracture, and to investigate hUCMSC
      delivery for bone tissue engineering. In fast fracture, CPC with 15% chitosan and
      20% polyglactin fibers (CPC-chitosan-fiber scaffold) had flexural strength of
      26mPa, higher than 10mPa for CPC control (p<0.05). In cyclic loading, CPC
      chitosan-fiber specimens that survived 2x10(6) cycles had the maximum stress of
      10MPa, compared to 5MPa of CPC control. CPC-chitosan-fiber specimens that failed
      after multiple cycles had a mean stress-to-failure of 9MPa, compared to 5.8MPa
      for CPC control (p<0.05). hUCMSCs showed excellent viability when seeded on CPC
      and CPC-chitosan-fiber scaffolds. The percentage of live cells reached 96-99%.
      Cell density was about 300cells/mm(2) at day 1; it proliferated to 700cells/mm(2)
      at day 4. Wst-1 assay showed that the stronger CPC-chitosan-fiber scaffold had
      hUCMSC viability that matched the CPC control (p>0.1). In summary, this study
      showed that chitosan and polyglactin fibers substantially increased the fatigue
      resistance of CPC, and that hUCMSCs had excellent proliferation and viability on
      the scaffolds.

PMID- 19850338
TI  - Biodegradable branched poly(ethylenimine sulfide) for gene delivery.
AB  - We synthesized biodegradable b-PEIS (branched poly(ethylenimine sulfide)) by
      crosslinking linear PEIS. We controlled the degree of crosslinking and molecular
      weight by adjusting the amount of the crosslinker, bisepoxide. The b-PEIS was
      readily degradable under reductive conditions (5mm glutathione solution) and the
      degradation time was dependent on the degree of crosslinking. We controlled the
      molecular weights of the b-PEIS by regulating the amount of crosslinker and thus,
      the degree of crosslinking. Our titration data showed that there was almost no
      loss in buffering ability before or after bisepoxide crosslinking. We verified
      the degradation of this polymer by MALLS and gel electrophoresis, and confirmed
      that there was a high transfection efficiency and low cytotoxicity based on
      cellular data. Intracellular trafficking was observed by image restoration
      microscopy, demonstrating that b-PEIS does not accumulate in the cell interior.

PMID- 19850339
TI  - A review of implantation and early placentation in the mare.
AB  - Constant, self induced mobility throughout the uterine lumen between days 6 and
      17 after ovulation, complete envelopment by a self-secreted glycoprotein capsule
      between days 7 and 30 and 'injection' of specialised, gonadotrophin-secreting
      trophoblast cells into the maternal endometrium at days 35-37 are three unusual
      aspects of equine embryogenesis. The outer trophoblast layer of the
      allantochorion finally establishes a stable, microvillous contact with the
      lumenal epithelium of the endometrium around days 40-42 and placentation
      commences thereafter. The allantochorion elongates steadily until it occupies the
      whole of the interior of the uterus by day 85. It develops branched, sub-branched
      and highly convoluted microcotyledons over its entire surface and these
      interdigitate closely with accommodating endometrial upgrowths (sulci) to provide
      a total microscopic area of fetomaternal contact for haemotrophic exchange which
      exceeds 50m(2) at term. Endometrial gland exocrine secretions, imbibed by
      elongated trophoblast cells that form areolae above the mouths of the endometrial
      glands, contribute histotrophic nutrients to the fetus throughout gestation.
      These dual forms of haemotrophic and histotrophic nutrition achieve a high degree
      of precocity in the foal at birth. This paper describes the gross and microscopic
      changes at the fetomaternal interface between days 20 and 80 of gestation in the
      pregnant mare which establishes the extensive, diffuse, non-invasive
      microcotyledonary placenta that supports fetal growth and development thereafter.

PMID- 19850340
TI  - Environmental education evaluation: time to reflect, time for change.
AB  - Evaluation in environmental education is fairly nascent despite decades-long
      attention to its importance. In setting the context for future chapters appearing
      in this special issue of the Journal of Evaluation and Program Planning,
      attention is devoted to the political circumstances associated with retrenchment
      in the public sector and increased involvement of citizens in environmental
      issues in their regions. It further is nested in the context of potential
      political reforms in a stable market democracy where education is but one
      strategy that can be bundled with regulations and taxes/subsidies. Additional
      attention is directed to explaining many of the key evaluation theories-
      utilization-focused evaluation, evaluative capacity building, and program-theory
      driven evaluation. The final section of this chapter situates the subsequent
      chapters of this volume based on the demographic target (youth or adult) as well
      as connection to a particular evaluation theory.

PMID- 19850341
TI  - Locating the system in a system of care.
AB  - While systems of care are recognized as a systems-level intervention, a gap
      remains between systems theory and practice that challenges the effectiveness of
      future system of care efforts. This article explores the extent to which the
      expanded system of care definition proposed by Hodges et al. [Hodges, S.
      Ferreira, K., Israel, N., & Mazza, J. (this issue). Systems of care, featherless
      bipeds, and the measure of all things. Evaluation and Program Planning] addresses
      this gap and suggests ideas for strengthening its systemic focus. Specifically,
      recommendations address considerations for assigning and adapting appropriate
      boundaries around intervention efforts and leveraging critical system
      characteristics and interactions to promote systems change. Implications for
      system of care practice and theory are discussed.

PMID- 19850342
TI  - Fractured hips: surgical authority, futility and innovation in nineteenth century
      medicine.
AB  - Orthopaedists have long found hip fractures to be a significant source of
      clinical uncertainty and professional disagreement. For much of the nineteenth
      century, surgeons were happy to follow Sir Astley Cooper's directive to 'treat
      the patient and let the fracture go'. Most sufferers were elderly, near the end
      of their lives and at significant risk from morbid complications. This palliative
      posture was further justified by a substantial corpus of medical evidence. Any
      attempt at therapeutic innovation was unwarranted because clinical experience,
      post-mortem studies and animal experiments indicated that fractures within the
      hip joint never healed. Yet as there were isolated cases of intra-capsular
      healing, surgeons such as Nicholas Senn began to contest this evidence. To his
      consternation, as he tried to demonstrate the possibility of restorative
      treatments, Senn found the fundamental problem with hip fractures was that the
      empiricism of current clinical methods created and perpetuated their own
      therapeutic justifications.

PMID- 19850343
TI  - Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a Factor
      H, FHL-1 and plasminogen binding surface protein.
AB  - The pathogenic yeast Candida albicans utilizes human complement regulators, like
      Factor H and Factor H like protein-1 (FHL-1) for immune evasion. By screening a
      C. albicans cDNA expression library, we identified the pH-regulated antigen 1
      (Pra1) as a novel Factor H and FHL-1 binding protein. Consequently Pra1 was
      recombinantly expressed in Pichia pastoris and purified from culture supernatant.
      Recombinant Pra1 binds Factor H, FHL-1 and also plasminogen. Attached to Pra1,
      the three human proteins are functionally active. Factor H and FHL-1 inactivate
      complement and plasminogen can be activated to plasmin which then degrades the
      extra-cellular matrix component fibrinogen. Polyclonal Pra1 anti-serum was
      generated and used to localize Pra1 on the surface and also in the culture
      supernatant of both yeast cells and the hyphal form of C. albicans. Furthermore
      Pra1 expression was up-regulated upon induction of hyphal growth. Pra1, released
      by Candida cells binds back to the surface of Candida hyphae and in addition
      enhances the complement regulatory activity of Factor H in the fluid phase. A
      Pra1 overexpression strain, with about twofold higher levels of Pra1 on the
      surface binds more Factor H, and plasminogen. In summary, C. albicans Pra1 is a
      yeast immune evasion protein that binds host immune regulators and acts at
      different sites. As a surface protein, Pra1 acquires the two human complement
      regulators Factor H, FHL-1 and plasminogen, mediates complement evasion, as well
      as extra-cellular matrix interaction and/or degradation. As a released protein,
      Pra1 enhances complement control in direct vicinity of the yeast and thus
      generates an additional protective layer which controls host complement attack.

PMID- 19850344
TI  - Cloning, expression and functional characterization of chicken CCR6 and its
      ligand CCL20.
AB  - Chemokines are key molecules that drive migration of lymphoid and myeloid cells
      toward organs in basal as well as inflammatory conditions. By recruiting immature
      dendritic cells to the mucosal surfaces, CCL20 acts in the very early events
      leading to the development of a specific immune response. In order to
      characterize dendritic cells in birds and better understand their role in the
      initiation of immune responses against pathogens of economic as well as human
      health relevance, we have cloned and expressed chicken CCL20 (chCCL20) and its
      specific receptor chCCR6. chCCL20 has 51% identity (60% similarity) with human
      CCL20, while the chicken receptor and its human counterpart display nearly 55%
      identity (and up to 70% similarity). chCCL20 and its specific receptor chCCR6
      mRNAs are mainly expressed in bone marrow, secondary lymphoid organs and in the
      mucosal surfaces, in particular lungs and intestine. Both receptor and chemokine
      are functionally active when expressed as genuine or tagged proteins in mammalian
      expression systems, that is chCCR6 is mainly located at the cell surface within
      lipid rafts like its human counterpart. And secondly, both human and chicken
      chemokines were able to drive the migration of either chicken or human CCR6
      transfected cells.

PMID- 19850345
TI  - Thymulin and zinc (Zn2+)-mediated inhibition of endotoxin-induced production of
      proinflammatory cytokines and NF-kappaB nuclear translocation and activation in
      the alveolar epithelium: unraveling the molecular immunomodulatory, anti
      inflammatory effect of thymulin/Zn2+ in vitro.
AB  - The immunomodulatory potential of thymulin and zinc (Zn(2+)) in the perinatal
      alveolar epithelium is not well characterized. In an in vitro model of fetal
      alveolar type II epithelial cells (FATEII), we have investigated the exhibition
      of an anti-inflammatory activity of this peptide hormone. Thymulin selectively
      ameliorated, in a dose-dependent manner, the endotoxin (ET/LPS
      [lipopolysaccharide])-induced release of IL-1beta, but not IL-6 or TNF-alpha.
      Furthermore, Zn(2+), an anti-inflammatory antioxidant, which is required for the
      biological activity of thymulin, independently reduced the secretion of IL-1beta,
      TNF-alpha and, to a lesser extent, at a supraphysiologic dose (1 mM), IL-6. The
      underlying cellular and molecular pathways associated with the anti-inflammatory
      effect of thymulin and Zn(2+) in the alveolar epithelium are not well
      established. Further in this study, the role of cyclic AMP (cAMP) in the anti
      inflammatory effect of thymulin was investigated, in addition to unraveling the
      possible involvement of the NF-kappaB pathway. Interestingly, thymulin
      upregulated, in a dose- and time-dependent manner, the release of the nucleotide
      cAMP. To understand whether the inhibitory effect of thymulin on cytokine release
      is cAMP-dependent, Forskolin, a labdane diterpene known to elevate intracellular
      cAMP, was shown to reduce the secretion of IL-1beta and TNF-alpha, but not IL-6,
      an effect mimicked by dibutyryl-cAMP (dbcAMP), an analog of cAMP. Alveolar
      epithelial cells treated with thymulin markedly showed a downregulation of the
      nuclear translocation of RelA (p65), the major transactivating member of the NF
      kappaB family, in addition to NF-kappaB(1) (p50) and c-Rel (p75), an effect
      mildly substantiated with Zn(2+). Furthermore, thymulin/Zn(2+) reduced, in a dose
      dependent manner, the DNA-binding activity of NF-kappaB (RelA/p65). These results
      indicate that the anti-inflammatory effect of thymulin, which is mediated by
      cAMP, is NF-kappaB-dependent and involves the downregulation of the release of
      proinflammatory cytokines, particularly IL-1beta, an effect synergistically
      amplified, at least in part, by Zn(2+). The molecular regulation of thymulin via
      a NF-kappaB-dependent pathway is critical to understanding the anti-inflammatory
      alleviating role of this nonapeptide in regulating proinflammatory signals.

PMID- 19850346
TI  - Intraoperative pachymetric measurements during corneal collagen cross-linking
      with riboflavin and ultraviolet A irradiation.
AB  - OBJECTIVE: To study central corneal pachymetric variations during corneal
      collagen cross-linking (CXL) treatment with the use of riboflavin and ultraviolet
      A irradiation (UVA). DESIGN: Prospective, noncomparative, interventional clinical
      study. PARTICIPANTS: Fifteen keratoconic patients (19 eyes) were enrolled.
      METHODS: All patients underwent riboflavin-UVA-induced corneal CXL.
      Intraoperative central corneal thickness (CCT) measurements using ultrasound
      pachymetry were performed during the procedure. Measurements were obtained after
      epithelial removal, after riboflavin drop instillation, and every 5 minutes (6
      interval times) during UVA irradiation (30 minutes). MAIN OUTCOME MEASURES:
      Central corneal thickness measurements. RESULTS: Mean patient age was 26.9+/-6.5
      years (range, 17-40 years). Ten were male and 5 were female. Mean preoperative
      CCT was 458.5+/-21.5 microm (range, 427-494 microm; 95% confidence interval [CI],
      448-467 microm) and 415.7+/-20.6 microm (range, 400-468 microm; 95% CI, 406-426
      microm) before and after epithelial removal, respectively. There was a
      statistically significant decrease (mean, 75 microm) of CCT between the
      epithelial removal interval (415.7+/-20.6 microm; range, 400-468 microm) and at
      the end of riboflavin solution instillation (340.7+/-22.9 microm; range, 292-386
      microm; P<0.001). There was no statistically significant change in CCT during
      irradiation (P>0.05). There was no statistically significant difference between
      preoperative and 1-month postoperative endothelial cell count (preoperative,
      2780+/-197 to 1-month postoperative, 2713+/-116; P = 0.14). No intraoperative,
      early postoperative, or late postoperative complications were observed in this
      patient series. CONCLUSIONS: During corneal CXL with the use of riboflavin and
      UVA irradiation, a statistically significant decrease of CCT was demonstrated.

PMID- 19850348
TI  - Diurnal intraocular pressure fluctuation and associated risk factors in eyes with
      angle closure.
AB  - OBJECTIVE: To investigate diurnal intraocular pressure (IOP) fluctuation in eyes
      with angle closure in comparison with normal subjects and to look for associated
      risk factors for IOP fluctuation. DESIGN: Prospective, cross-sectional study.
      PARTICIPANTS: Ninety-eight eyes of 98 Asian subjects with angle closure
      (consisting of 32 primary angle-closure suspects [PACS], 34 subjects with primary
      angle closure [PAC], and 32 subjects with primary angle-closure glaucoma [PACG])
      and 21 eyes of 21 normal control subjects. METHODS: All angle-closure subjects
      were enrolled after laser peripheral iridotomy but before commencement of any
      medical or surgical treatment. Ophthalmic examination, including dynamic
      gonioscopy and automated perimetry, were performed, and diurnal IOP measurements
      were obtained using noncontact air-puff tonometry at hourly intervals between
      8:00 am and 5:00 pm. Mean diurnal IOP, peak diurnal IOP, trough IOP, and IOP
      fluctuation (peak IOP-trough IOP) were compared between groups. Multiple linear
      regression analysis was performed to study the association of IOP fluctuation
      with clinical variables such as age, extent of peripheral anterior synechiae
      (PAS), central corneal thickness, vertical cup-to-disc ratio, and pattern
      standard deviation (PSD) on automated perimetry. MAIN OUTCOME MEASURES: Mean
      diurnal IOP, peak IOP, and IOP fluctuation. RESULTS: Most subjects were Chinese
      (89.1%) and female (61.3%). Intraocular pressure fluctuation was significantly
      higher in PACG (5.4+/-2.4 mmHg) and PAC (4.5+/-2.3 mmHg) subjects compared with
      PACS subjects (3.7+/-1.2 mmHg) and normal controls (3.8+/-1.1 mmHg; P = 0.005),
      with highest IOP found in the early morning. The combined PACG and PAC group had
      more than twice the risk (odds ratio, 2.38; 95% confidence interval, 1.1-5.1; P =
      0.025) of having IOP fluctuation of more than 3 mmHg compared with the combined
      PACS and normal group. Extent of PAS (Pearson's correlation coefficient, r =
      0.37; P = 0.0001) and visual field PSD (r = 0.34; P = 0.0002) were found to be
      associated with greater IOP fluctuation. CONCLUSIONS: The PACG and PAC eyes
      showed diurnal IOP fluctuation of 4 to 5 mmHg, and this fluctuation was higher
      than in PACS subjects and normal controls. The degree of PAS and visual field
      loss were associated with IOP fluctuation in PAC and PACG eyes.

PMID- 19850347
TI  - Statin use and the incidence of advanced age-related macular degeneration in the
      Complications of Age-related Macular Degeneration Prevention Trial.
AB  - OBJECTIVE: To evaluate the impact of statin use on the incidence of advanced age
      related macular degeneration (AMD) and its components, choroidal
      neovascularization (CNV) and geographic atrophy (GA), among patients with
      bilateral large drusen. DESIGN: Cohort study within a multicenter, randomized,
      clinical trial. PARTICIPANTS: Patients enrolled in the Complications of Age
      related Macular Degeneration Prevention Trial (CAPT). METHODS: Eligibility
      criteria for the clinical trial required that participants have >or=10 large
      (>125 microm) drusen and visual acuity >or=20/40 in each eye. Patients scheduled
      for their final CAPT visit after May 2005 were interviewed on their history of
      use of cholesterol-lowering medications, including statins. Trained readers
      identified CNV and end point GA (>1 Macular Photocoagulation Study disc area of
      GA) based on review of fluorescein angiograms and fundus photographs taken at
      annual follow-up visits and when patients reported symptoms. The risk ratio for
      participants developing CNV or developing GA associated with statin use was
      estimated with time-dependent Cox proportional hazards models. MAIN OUTCOME
      MEASURES: Development of advanced AMD, CNV, and end point GA. RESULTS: Among 764
      patients eligible for the interview, 744 (97.4%) patients completed the interview
      on medication use. Statin use was reported by 296 (39.8%) of those interviewed,
      with the majority, 187 (63.2%) of the 296, beginning use after enrollment in
      CAPT. Among 744 patients, advanced AMD developed in 332 (22.5%) eyes of 242
      (32.5%) patients, CNV in 222 (15%) eyes of 176 (23.7%) patients, and GA in 114
      (7.7%) eyes of 80 (10.8%) patients. With adjustment for other risk factors, the
      estimated risk ratio for eyes (95% confidence interval) associated with statin
      use was 1.15 (0.87-1.52) for advanced AMD, 1.35 (0.99-1.83) for CNV, and 0.80
      (0.46-1.39) for GA. CONCLUSIONS: The CAPT data are not consistent with a strong
      protective effect (risk ratio, <or=0.85) of statins on the development of
      advanced AMD among patients with bilateral large drusen.

PMID- 19850349
TI  - Ligand orientation of human neuroglobin obtained from solution NMR and molecular
      dynamics simulation as compared with X-ray crystallography.
AB  - Neuroglobin, a new member of hemoprotein family, can reversibly bind oxygen and
      take part in many biological processes such as enzymatic reaction, signal
      transduction and the mitochondria function. Different from myoglobin and
      hemoglobin, it has a hexacoordinated heme environment, with histidyl imidazole of
      proximal His(96)(F8) and distal His(64)(E7) directly bound to the metal ion. In
      the present work, solution (1)H NMR spectroscopy was employed to investigate the
      electronic structure of heme center of wild-type met-human neuroglobin. The
      resonances of heme protons and key residues in the heme pocket were assigned. Two
      heme orientations resulting from a 180 degrees rotation about the alpha-gamma
      meso axis with a population ratio about 2:1 were observed. Then the (1)H NMR
      chemical shifts of the ferriheme methyl groups were used to predict orientations
      of the axial ligand. The obtained axial ligand plane angle phi is consistent with
      that from the molecular dynamics simulation but not with those from the crystal
      data. Compared with mouse neuroglobin, the obtained average ligand orientation of
      human neuroglobin reflects the changeability of heme environment for the Ngb
      family.

PMID- 19850350
TI  - Siderophore-mediated iron acquisition in the staphylococci.
AB  - Iron is frequently a growth-limiting nutrient due to its propensity to interact
      with oxygen to form insoluble precipitates and, therefore, biological systems
      have evolved specialized uptake mechanisms to obtain this essential nutrient.
      Many pathogenic bacteria are capable of obtaining stringently sequestered iron
      from animal hosts by one or both of the following mechanisms: extraction of heme
      from host erythrocyte and serum hemoproteins, or through the use of high
      affinity, iron-scavenging molecules termed siderophores. This review summarizes
      our current knowledge of siderophore-mediated iron acquisition systems in the
      genus Staphylococcus.

PMID- 19850351
TI  - Effects of decavanadate and insulin enhancing vanadium compounds on glucose
      uptake in isolated rat adipocytes.
AB  - The effects of different vanadium compounds namely pyridine-2,6
      dicarboxylatedioxovanadium(V) (V5-dipic), bis(maltolato) oxovanadium(IV) (BMOV)
      and amavadine, and oligovanadates namely metavanadate and decavanadate were
      analysed on basal and insulin stimulated glucose uptake in rat adipocytes.
      Decavanadate (50 microM), manifest a higher increases (6-fold) on glucose uptake
      compared with basal, followed by BMOV (1 mM) and metavanadate (1 mM) solutions (3
      fold) whereas V5 dipic and amavadine had no effect. Decavanadate (100 microM)
      also shows the highest insulin like activity when compared with the others
      compounds studied. In the presence of insulin (10 nM), only decavanadate
      increases (50%) the glucose uptake when compared with insulin stimulated glucose
      uptake whereas BMOV and metavanadate, had no effect and V5 dipic and amavadine
      prevent the stimulation to about half of the basal value. Decavanadate is also
      able to reduce or eradicate the suppressor effect caused by dexamethasone on
      glucose uptake at the level of the adipocytes. Altogether, vanadium compounds and
      oligovanadates with several structures and coordination spheres reveal different
      effects on glucose uptake in rat primary adipocytes.

PMID- 19850353
TI  - QM/MM study of the insertion of metal ion into protoporphyrin IX by
      ferrochelatase.
AB  - Ferrochelatase catalyzes the metallation of protoporphyrin IX in the terminal
      step of heme biosynthesis. Mutations in the ferrochelatase gene can lead to the
      disease erythropoietic porphyria. The catalyzing mechanism of ferrochelatase is
      still not fully understood. In this paper, we have studied the insertion of
      Fe(2+) into the protoporphyrin IX ring by Bacillussubtilis ferrochelatase using
      combined quantum mechanical and molecular mechanics (QM/MM) calculations.
      Geometries were optimized at the BP86/6-31G * level and energies were calculated
      at the B3LYP/TZVP level. The overall process involves the stepwise displacement
      of Glu-264, His-183, and a water molecule from Fe(2+), and the removal of two
      protons from the porphyrin ring. The rate-determining step is the cleavage of the
      bond between the oxygen atom of Glu-264 and Fe(2+), concomitant with the
      formation of the first Fe-N bond. It has an energy barrier of 57 kJ mol(-1). The
      porphyrin ring is only slightly distorted in the enzyme active site. The residue
      Tyr-13 plays a key role for the catalytic process extracting two protons from
      protoporphyrin IX.

PMID- 19850352
TI  - Complexation of bisphosphonates with ytterbium(III): application of phosphate and
      ATP detection assay based on Yb(3+)-pyrocatechol violet.
AB  - The coordination chemistry of bisphosphonates with Yb(3+) was investigated to
      evaluate the potential of the UV-vis based detection method using the Yb(3+)
      pyrocatechol complexation reaction as a sensor for bisphosphonates. The
      complexation chemistry of Yb(3+) with phosphate and ATP analogs was previously
      described (E. Gaidamauskas, K. Saejueng, A.A. Holder, S. Bharuah, B.A.
      Kashemirov, D.C. Crans, C.E. McKenna, J. Biol. Inorg. Chem. 13 (2008) 1291-1299),
      and we here studied the complexation chemistry of bisphosphonates in this system.
      The spectrophotometric assay yields direct evidence for formation of a 4:3 metal
      to ligand complex at neutral pH. Direct evidence for
      Yb(3+):methylenebis(phosphonate) complexes with 1:1 and 1:2 stoichiometry was
      also obtained by potentiometry at acidic and basic pH. Direct evidence for
      complex formation was obtained using (1)H NMR spectroscopy although the
      stoichiometry was not accessed at neutral pH. Our results suggest that the
      spectroscopic observation of the YbPV complex can be used to conveniently measure
      concentrations of bisphosphonates down to 2-3 microM.

PMID- 19850354
TI  - Human zona pellucida glycoproteins: functional relevance during fertilization.
AB  - The zona pellucida (ZP), a glycoproteinaceous matrix surrounding the mammalian
      oocyte plays an important role in species-specific sperm-egg binding, induction
      of acrosome reaction in the ZP-bound spermatozoa, avoidance of polyspermy and
      protection of the embryo prior to implantation. In contrast to mouse, human ZP
      matrix is composed of 4 glycoproteins designated as ZP1, ZP2, ZP3 and ZP4 (Zp4
      pseudogene in mouse). Recent studies employing recombinant and immunoaffinity
      purified human zona proteins revealed that in addition to ZP3, capacitated
      acrosome-intact spermatozoa also bind ZP4. Human ZP2 primarily binds to the
      acrosome-reacted spermatozoa, supporting its role as secondary sperm receptor, as
      delineated in the murine model. For binding of human zona proteins to
      spermatozoa, glycosylation is not critical. Both human ZP3 and ZP4 induce dose
      dependent acrosomal exocytosis in capacitated sperm. In contrast to the murine
      model, N-linked glycosylation is more critical for the human ZP3/ZP4 mediated
      induction of acrosomal exocytosis. Subtle differences in the downstream signaling
      events associated with ZP3 vs. ZP4 mediated induction of acrosomal exocytosis
      have been observed. To conclude, in humans, ZP3 and ZP4 are involved in binding
      of the spermatozoa to the egg and subsequent induction of acrosome reaction. The
      contribution, if any, of human ZP glycoprotein-1 (ZP1) during these stages of
      fertilization remains to be elucidated.

PMID- 19850355
TI  - The practical side of immunocontraception: zona proteins and wildlife.
AB  - With shrinking habitat, the humane control of certain wildlife populations is
      relevant. The contraceptive vaccine based on native porcine zona pellucida (PZP)
      has been applied to various wildlife populations for 20 years. Prominent efforts
      include wild horses, urban deer, zoo animals and African elephants, among others.
      This approach has been successful in managing entire populations and to date, no
      significant debilitating short- or long-term health effects have been documented.

PMID- 19850357
TI  - Toll-like receptor signaling in bony fish.
AB  - The innate immune system constitutes an efficient defense against invading
      microbial pathogens. Toll-like receptors (TLRs) eventually alert vertebrates
      about the presence of pathogens and elicit the immune responses. To date, 17
      different TLRs have been identified in more than a dozen different fish species.
      Numerous studies revealed that specific piscine TLRs share functional properties
      with their mammalian counterparts. Nevertheless, remarkable distinct features of
      teleostean Toll-like receptor cascades have been discovered. A soluble TLR5
      factor in rainbow trout for example might amplify danger signaling of membrane
      bound TLR5 in a positive feed loop. Piscine TLR3 detects viral and additionally
      bacterial molecular patterns in contrast to mammalian TLR3. Regarding TLR4, the
      functional spectrum of this teleostean receptor is also different from its
      mammalian orthologue. While signaling quite similar as the mammalian counterpart
      in some fish species, it may down-regulate TLR activation in others or was even
      lost during evolution. The orthologues of human TLR6 and TLR10 are also absent in
      teleosts. Some piscine TLRs are encoded by duplicated genes, for example salmonid
      TLR22. TLR22 is found in several fish species but only as a non-functional
      pseudogene in man. Additional distinct features of the TLR pathway in bony fish
      suggest its specific optimization for the aquatic environment. This review
      summarizes studies characterizing TLRs from several teleost species and discusses
      features of piscine TLR signaling on the background of the respective mammalian
      knowledge.

PMID- 19850358
TI  - Neuroimmunologia: heri, hodie et cras.

PMID- 19850356
TI  - Impact of T. vaginalis infection on innate immune responses and reproductive
      outcome.
AB  - Trichomonas vaginalis is the most common non-viral sexually transmitted pathogen.
      The infection is prevalent in reproductive age women and is associated with
      vaginitis, endometritis, adnexitis, pyosalpinx, infertility, preterm birth, low
      birth weight, bacterial vaginosis, and increased risk of cervical cancer, HPV,
      and HIV infection. In men, its complications include urethritis, prostatitis,
      epididymitis, and infertility through inflammatory damage or interference with
      the sperm function. The infection is often asymptomatic and recurrent despite the
      presence of specific antibodies, suggesting the importance of the innate immune
      defense. T. vaginalis adhesion proteins, cysteine proteases, and the major
      parasite lipophosphoglycan (LPG) play distinct roles in the pathogenesis and
      evasion of host immunity. LPG plays a key role in the parasite adherence and
      signaling to human vaginal and cervical epithelial cells, which is at least in
      part mediated by galectins. The epithelial cells respond to T. vaginalis
      infection and purified LPG by selective upregulation of proinflammatory
      mediators. At the same time, T. vaginalis triggers an immunosuppressive response
      in monocytes, macrophages, and dendritic cells. The molecular mechanisms
      underlying reproductive complications and epidemiologic risks associated with T.
      vaginalis infection remain to be elucidated.

PMID- 19850359
TI  - Western blot analysis for the detection of serum antibodies recognizing linear
      Aquaporin-4 epitopes in patients with Neuromyelitis Optica.
AB  - The current study presents a western blot assay showing good sensitivity (81%)
      and specificity (97%) for detecting serum antibodies to Aquaporin-4 (AQP4) in
      patients with Neuromyelitis Optica (NMO). By using western blot, we were able,
      for the first time, to distinguish serum immunoreactivity against either of the
      two AQP4 isoforms, showing that antibodies recognizing the linear AQP4-M1 isoform
      are specific for NMO. Moreover, the high sensitivity and specificity of the
      western blot assay in detecting serum anti-AQP4 antibodies in NMO patients
      suggest that such auto-antibodies may be of linear nature, thus recognizing
      epitopes that are displayed in denatured protein.

PMID- 19850360
TI  - Long-term toxicity of hexabromocyclododecane (HBCDD) to the benthic clam Macoma
      balthica (L.) from the Baltic Sea.
AB  - The world's largest brackish water sea area, the Baltic Sea, is considered to be
      one of the most polluted seas of the world. Many new pollutants are constantly
      entering the environment, such as brominated flame-retardants (BFRs). BFRs
      represent a group of compounds that structurally resemble hydrophobic organic
      contaminants, but only scarce data about their toxicity to marine organism exist.
      Thus, the purpose of this study was to analyze long-term in vivo cytotoxicity and
      genotoxicity of hexabromocyclodododecane (HBCDD) to exposed marine invertebrates
      using a suite of cytogenetic biomarkers. This included a set of nuclear and
      nucleolar characteristics and the micronucleus test. The use of those parameters
      reflects different mechanisms of nuclear activity regulation in cells (as a
      parameter of cytotoxicity) and measures subcellular processes. The induction of
      nuclear abnormalities (like the formation of micronuclei) was also employed here
      as a parameter of genotoxicity. In order to reflect the proliferative and
      metabolic activity of the cells the number of argylophillic nucleolar organiser
      regions (NORs) in interphase cells was scored. Over a period of 50 days an in
      vivo exposure experiment with a clam Macoma balthica and different concentrations
      of HBCDD (nominal concentrations of 0, 100 and 250microg/l) with three replicates
      each was performed. Gill cells were used as "sentinel systems" considering
      specificity in metabolism, repair mechanisms, adaptative response and cell
      proliferation. A significant increase in nuclear and nucleolar abnormalities and
      in the frequency of dead cells was observed during the duration of the experiment
      with the highest peak occurring 10 days after exposure for nuclear abnormalities
      and 20-30 days after exposure for malfunction of ribosomal genes (NORs) (GLM
      analyses and Spearman correlation, p<0.05). Thus, the induction of micronuclei
      and other nuclear abnormalities reflected the toxic potential of HBCDD to marine
      invertebrates while an increase in the number of NOR may also reflect adaptive
      responses of the system as enhanced induction of proliferative regeneration of
      the gill tissue.

PMID- 19850361
TI  - Interactive effects of infectious diseases and pollution in aquatic molluscs.
AB  - Aquatic molluscs are ideal invertebrate model systems for environmental
      monitoring and toxicology. However, like all animals, they are subjected to a
      wide range of infectious diseases that can have significant effects on host
      ecology and physiology and are therefore a source of natural stress to
      populations. Anthropogenic activities, especially involving chemical contaminants
      that pollute the environment, can also affect molluscan ecological and
      physiological parameters. In combination, pollution and pathogens represent a
      serious threat to the health of aquatic communities that has been increasingly
      recognised. The present article reviews the interactive effects of viral,
      bacterial, protozoan, and trematode infections with toxic pollutants on aquatic
      molluscs. The interactions between pollution and other less well studied
      infectious diseases as well as the differing responses to pathogens and pollution
      between wild and cultured molluscan populations are also considered.

PMID- 19850362
TI  - Assessment of tissue-specific accumulation and effects of cadmium in a marine
      fish fed contaminated commercially produced diet.
AB  - Commercially produced fish diet is now widely used in fish farming but it often
      contains elevated levels of cadmium (Cd). However, the adverse effects on fish
      are poorly understood. In this study, farm-raised marine grunts, Terapon jarbua,
      were fed Cd-contaminated diet or exposed to waterborne Cd for 4 weeks. Tissue
      specific Cd bioaccumulation and its effects were subsequently examined. We found
      that Cd was accumulated in different fish tissues (digestive tracts, gills or
      livers). At the end of the exposure, Cd accumulation peaked in the fishes' livers
      (5.0-6.3microgg(-1)), followed by the digestive tracts (0.83-3.16microgg(-1)) and
      gills (0.27-2.74microgg(-1)). Endpoints such as the survival rate, specific
      growth rate, condition factor, and superoxide dismutase activity were not
      significantly affected by Cd exposure. In contrast, metallothionein (MT)
      induction and subcellular Cd distribution indicated that there were possible
      sublethal effects of Cd exposure. MT was induced in response to Cd accumulation,
      but it returned to the control levels after a longer exposure period, except for
      hepatic MT induction resulting from waterborne or low dietary Cd exposure. The Cd
      percentage in the metallothionein-like protein (MTLP) fraction increased over
      exposure time, and it accounted for more than 57% Cd in the fishes' livers and
      80% Cd in their digestive tracts by the end of the exposure period. Overall,
      although Cd in commercial fish diet did not have significant lethality to T.
      jarbua, sensitive responses such as hepatic MT induction and subcellular Cd
      distribution revealed that the Cd-induced storage and detoxification in T. jarbua
      may increase fish's tolerance to toxic metals.

PMID- 19850363
TI  - Characterization of the metabolic actions of crude versus dispersed oil in salmon
      smolts via NMR-based metabolomics.
AB  - With maritime transport of crude oil from Alaska to California, there is
      significant potential for a catastrophic spill which could impact migrating
      salmon. Therefore, this study compared the lethal and sublethal metabolic actions
      of the water-accommodated fraction (WAF) and the chemically enhanced WAF (CEWAF,
      via Corexit 9500) of Prudhoe Bay crude oil in smolts of Chinook salmon
      (Onchorhyncus tshawytscha). After 96-h exposure to the CEWAF, the resulting LC50
      was some 20 times higher (i.e., less toxic) than that of the WAF. Muscle and
      liver samples from surviving fish were collected and low-molecular weight
      metabolites were analyzed using one-dimensional (1)H and projections of two
      dimensional (1)H J-resolved NMR. Principal component analysis (PCA), employed to
      analyze NMR spectra and identify most variance from the samples, revealed age
      related metabolic changes in the fish within the replicated studies, but few
      consistent metabolic effects from the treatments. However, ANOVA results
      demonstrated that the dose-response metabolite patterns are both metabolite- and
      organ-dependent. In general, exposure to either WAF or CEWAF resulted in an
      increase of amino acids (i.e., valine, glutamine and glutamate) and a decrease of
      both organic osmolytes (i.e., glycerophosphorylcholine) and energetic substrates
      (i.e., succinate). The simultaneous increase of formate and decrease of
      glycerophosphorylcholine in the liver, or the decrease of
      glycerophosphorylcholine in muscle, may serve as sensitive sublethal biomarkers
      for WAF or CEWAF exposures, respectively. In conclusion, dispersant treatment
      significantly decreased the lethal potency of crude oil to salmon smolts, and the
      NMR-based metabolomics approach provided a sensitive means to characterize the
      sublethal metabolic actions.

PMID- 19850364
TI  - Generation of a fluorescent transgenic zebrafish for detection of environmental
      estrogens.
AB  - To establish a novel in vivo test system for rapid detection of environmental
      estrogens, an ere-zvtg1: gfp transgenic zebrafish line has been generated. In
      this transgenic line, under control conditions, GFP was exclusively expressed in
      the liver of mature adult female fish. Male and larval transgenic fish did not
      express GFP but could be induced to express GFP in the liver after exposure to 17
      alpha-ethynylestradiol (EE(2)). Concurrent accumulation of zvtg1 and gfp mRNAs in
      embryos and larvae after EE(2) exposure was observed, which indicated that the
      expression of gfp transgene was driven by the zvtg1 promoter. Green fluorescence
      was first observed in the liver at 53, 74, 100 or 131h post-fertilization (hpf)
      after exposure to 100, 10, 1 or 0.1ng/L EE(2) from 1 to 2 cell stage,
      respectively. As for mature male transgenic zebrafish, green fluorescence was
      observed after exposure to 100, 10, 1 or 0.1ng/L EE(2) for 2, 3, 4 or 7 days,
      respectively; as for mature female, fluorescence was increased after exposure to
      relatively high concentrations of EE(2) (10 and 100ng/L). Green fluorescence in
      the liver was increased with prolonging of exposure time and was repeatedly
      induced after removal and re-addition of EE(2). We also demonstrated that GFP
      expression could be induced by other estrogenic compounds, including beta
      estradiol (E(2), 0.1microg/L), cadmium chloride (CdCl(2), 10microg/L),
      zearalenone (50microg/L), estriol (E(3), 1microg/L), diethylstilbestrol (DES,
      50ng/L) bisphenol A (BPA, 1mg/L) but not by weakly estrogenic compounds such as
      nonylphenol (NP, up to 10mg/L), or non-estrogenic steroid hormones such as
      progesterone (up to 100mg/L) and 17-hydroxysteroid (up to 50mg/L). These data
      suggest the transgenic zebrafish is sensitive and specific for detection of
      estrogenic compounds. Because the observed-effect concentrations are as low as
      those of environment and the observed-effect exposure times are very short, this
      transgenic fish is a promising candidate system for monitoring environmental
      estrogens directly, rapidly and easily.

PMID- 19850365
TI  - Developmental effects of a municipal wastewater effluent on two generations of
      the fathead minnow, Pimephales promelas.
AB  - Municipal wastewater effluents have been shown to contain a variety of
      anthropogenic compounds, many of which are known to display estrogenic
      properties. While multiple laboratory studies have shown the effects of such
      compounds on an individual basis at elevated concentrations, little research has
      attempted to characterize the effects of exposure to environmentally relevant
      mixtures of estrogenic compounds. The current study examined the effects of long
      term exposure to graded concentrations (0, 50, 100%) of wastewater effluent on
      the fathead minnow, Pimephales promelas. The F1 generation was cultured in
      control water to test for transgenerational effects from parental exposure to
      wastewater effluent. Total estrogenic activity in the wastewater was determined
      to be approximately 1.7ng/L 17beta-estradiol equivalents. Survival, growth, and
      reproduction in the parent generation were not affected by exposure to the
      wastewater treatments. An increase in the gonadosomatic index and a reduction in
      the expression of secondary sex characteristics in male fathead minnows exposed
      to 100% wastewater in the parent generation were observed. Conversely, the
      expression of secondary sex characteristics was greater in males from the F1
      generation of wastewater-exposed parents. Additionally, a positive relationship
      between parental exposure to wastewater and the onset of reproductive activity in
      the F1 generation was observed. Results of this study suggest that exposure to
      wastewater effluent did not pose a significant threat to the successful growth,
      development, and reproduction of the fathead minnow. Early onset of reproductive
      activity observed in the F1 generation of wastewater-exposed parents in
      subsequent generations should be studied further.

PMID- 19850366
TI  - The impact of infarct type on the reliability of early oral glucose tolerance
      testing in patients with myocardial infarction.
AB  - BACKGROUND: Previously unknown glucose perturbations are common in patients with
      myocardial infarction (MI). We evaluated the accuracy of an early oral glucose
      tolerance test OGTT in relation to the extent of the MI. MATERIAL AND METHODS: An
      OGTT was performed in 134 patients with MI without known diabetes (DM) after 4-5
      days (predischarge) and 3 months. The MI was classified as transmural (TMI; n=70)
      or subendocardial (SEMI; n=102). RESULTS: Predischarge TMI-patients had normal
      GT, impaired GT or DM in 31%, 33% and 36%. These proportions were 35%, 39% and
      26% after 3 months. The corresponding proportions in SEMI-patients were 35%, 35%
      and 30% and 35%, 40% and 25%. At admission and the first 2 days fasting glucose
      was higher in TMI than SEMI-patients. CONCLUSION: The outcome of an early OGTT is
      valid but the test should not be performed earlier than 4-5 days after the event
      especially in patients with extensive infarctions.

PMID- 19850367
TI  - Radiosensitivity of squamous cell carcinoma metastases to the neck assessed by
      immunocytochemical profiling of fine-needle aspiration biopsy cell specimens: a
      pilot study.
AB  - PURPOSE: To assess radiosensitivity of neck metastases of squamous cell carcinoma
      of the head and neck (SCCHN) by immunocytochemical profiling of fine-needle
      aspiration biopsy (FNAB) cell specimens. PATIENTS AND METHODS: Immunocytochemical
      reactions to p53, cyclin D1, stefin A and Ki-67 were determined in FNAB cell
      samples of neck metastases from 21 patients treated with concomitant
      chemoradiotherapy and correlated to clinical characteristics and response to
      therapy. RESULTS: Six (28.6%), eight (38.1%), 15 (71.4%) and nine (42.9%) FNAB
      cell samples were classified as p53, cyclin D1, stefin A and Ki-67 positive,
      respectively. Statistically significant predictors of favorable nodal response to
      chemoradiation were p53 (P=0.025) and cyclin D1 (cytoplasmic fraction, P=0.048)
      negativity and Ki-67 positivity (P=0.045). Regional recurrence correlated with
      low Ki-67 immunoreactivity. A favorable profile of cyclin D1 and Ki-67 (one or
      both of the two) further improved the predictive strength of these markers.
      CONCLUSIONS: FNAB is a non-invasive, simple and cheap procedure, which could
      serve simultaneously for diagnostic purposes and for radiosensitivity testing.
      Immunocytochemical determination of cyclin D1 and Ki-67 in FNAB cell samples from
      neck metastases of SCCHN seems to be a valuable marker for predicting regional
      response to radiotherapy and might assist when deciding on appropriate primary
      therapy.

PMID- 19850368
TI  - Monoallelic expression and tissue specificity are associated with high crossover
      rates.
AB  - What determines the recombination rate of a gene? Following the observation that,
      in humans, imprinted genes have unusually high recombination levels, we ask
      whether increased recombination is seen for other monoallelically expressed genes
      and, more generally, how transcriptional properties relate to recombination. We
      find that monoallelically expressed genes do have high crossover rates and
      discover a striking negative correlation between within-gene crossover rate and
      expression breadth. We hypothesise that these findings are possibly symptomatic
      of a more general, adverse relationship between recombination and transcription
      in the human genome.

PMID- 19850370
TI  - Chromatin indexing in Arabidopsis: an epigenomic tale of tails and more.
AB  - Packaging DNA into chromatin is pivotal for the regulation of genome activity in
      eukaryotes. This chromatin-level control relies on a range of histone
      modifications and variants, chromatin-remodeling proteins and DNA methylation in
      plants and mammals. High-resolution maps have recently been obtained for several
      chromatin modifications in Arabidopsis, which provide a first glimpse at the
      organization of plant epigenomes. These maps suggest a pervasive involvement of
      transcriptional activity in indexing chromatin with reference to the underlying
      DNA sequence. However, to assess the contribution of chromatin dynamics to plant
      development and phenotypic plasticity, it will be necessary to shift from a
      static to a dynamic view of the Arabidopsis epigenome.

PMID- 19850369
TI  - Primary microcephaly: do all roads lead to Rome?
AB  - The relatively large brain and expanded cerebral cortex of humans is unusual in
      the animal kingdom and is thought to have promoted our adaptability and success
      as a species. One approach for investigating neurogenesis is the study of
      autosomal recessive primary microcephaly (MCPH), in which prenatal brain growth
      is significantly reduced without an effect on brain structure. To date, eight
      MCPH loci and five genes have been identified. Unexpectedly, all MCPH proteins
      are ubiquitous and localise to centrosomes for at least part of the cell cycle.
      Here, we focus on recent functional studies of MCPH proteins that reveal the
      centrosome as a final integration point for many regulatory pathways affecting
      prenatal neurogenesis in mammals.

PMID- 19850371
TI  - Saturn: a software application of tensor utilities for research in neuroimaging.
AB  - We present an advanced software tool designed for visualization and quantitative
      analysis of Diffusion Tensor Imaging (DTI) called Saturn. The software is
      specially developed to help clinicians and researchers in neuroimaging, and
      includes a complete set of visualization capabilities to browse and analyze
      efficiently DTI data, making this application a powerful tool also for diagnosis
      purposes. The software includes a robust quantification method for DTI data,
      using an atlas-based method to automatically obtain equivalent anatomical fiber
      bundles and regions of interest among different DTI data sets. Consequently, a
      set of measurements is also implemented to perform robust group studies among
      subjects affected by neurological disorders and control groups in order to look
      for significant differences. Finally, a comparison study with five similar DTI
      applications is presented, showing the advantages offered by this tool.

PMID- 19850372
TI  - On the efficiency of iterative ordered subset reconstruction algorithms for
      acceleration on GPUs.
AB  - Expectation Maximization (EM) and the Simultaneous Iterative Reconstruction
      Technique (SIRT) are two iterative computed tomography reconstruction algorithms
      often used when the data contain a high amount of statistical noise, have been
      acquired from a limited angular range, or have a limited number of views. A
      popular mechanism to increase the rate of convergence of these types of
      algorithms has been to perform the correctional updates within subsets of the
      projection data. This has given rise to the method of Ordered Subsets EM (OS-EM)
      and the Simultaneous Algebraic Reconstruction Technique (SART). Commodity
      graphics hardware (GPUs) has shown great promise to combat the high computational
      demands incurred by iterative reconstruction algorithms. However, we find that
      the special architecture and programming model of GPUs add extra constraints on
      the real-time performance of ordered subsets algorithms, counteracting the
      speedup benefits of smaller subsets observed on CPUs. This gives rise to new
      relationships governing the optimal number of subsets as well as relaxation
      factor settings for obtaining the smallest wall-clock time for reconstruction-a
      factor that is likely application-dependent. In this paper we study the
      generalization of SIRT into Ordered Subsets SIRT and show that this allows one to
      optimize the computational performance of GPU-accelerated iterative algebraic
      reconstruction methods.

PMID- 19850373
TI  - Automatic segmentation of long-term ECG signals corrupted with broadband noise
      based on sample entropy.
AB  - Biomedical signals are nonstationary in nature, namely, their statistical
      properties are time-dependent. Such changes in the underlying statistical
      properties of the signal and the effects of external noise often affect the
      performance and applicability of automatic signal processing methods that require
      stationarity. A number of methods have been proposed to address the problem of
      finding stationary signal segments within larger nonstationary signals. In this
      framework, processing and analysis are applied to each resulting locally
      stationary segment separately. The method proposed in this paper addresses the
      problem of finding locally quasi-stationary signal segments. Particularly, our
      proposed algorithm is designed to solve the specific problem of segmenting
      semiperiodic biomedical signals corrupted with broadband noise according to the
      various degrees of external noise power. It is based on the sample entropy and
      the relative sensitivity of this signal regularity metric to changes in the
      underlying signal properties and broadband noise levels. The assessment of the
      method was carried out by means of experiments on ECG signals drawn from the MIT
      BIH arrhythmia database. The results were measured in terms of false alarms based
      on the changepoint detection bias. In summary, the results achieved were a
      sensitivity of 97%, and an error of 16% for records corrupted with muscle
      artifacts.

PMID- 19850374
TI  - Mandatory handwashing in elementary schools reduces absenteeism due to infectious
      illness among pupils: a pilot intervention study.
AB  - BACKGROUND: The objective of this study was to determine the effect of mandatory,
      scheduled handwashing on actual absenteeism due to infectious illness in
      elementary school pupils in Denmark. METHODS: A 3-month pilot intervention study,
      randomized between 2 schools, was performed on 652 pupils age 5 to 15 years. The
      pupils at the intervention school (IS; n=290) were required to wash their hands
      before the first lesson, before lunch, and before going home. Those at the
      control school (CS; n=362) continued their usual handwashing practices. All
      absences due to illness were recorded, and data were analyzed statistically.
      RESULTS: Multivariate analysis demonstrated a significantly reduced rate of
      absenteeism for the IS compared with the CS (P=.002). For girls, the rate was
      1.05 periods (95% confidence interval [CI]=0.90 to 1.22) for the IS versus 1.35
      (95% CI=1.26 to 1.44) for the CS. For boys, these rates were 0.87 (95% CI=0.72 to
      1.05) and 1.12 (95% CI=0.92 to 1.36). An alternative approach demonstrated that
      the odds ratio for absence was 0.69 (95% CI=0.52 to 0.92) for the IS compared
      with the CS. CONCLUSION: This study suggests that handwashing could be an
      effective tool to reduce absences due to infectious illness in elementary school
      pupils. A school policy regarding hand hygiene and teaching of hand hygiene is
      warranted.

PMID- 19850375
TI  - [Antimicrobials and pregnancy].
AB  - The physiologic changes that occur during pregnancy result in pharmacokinetic
      changes that can alter the effectiveness of antimicrobial agents. The possible
      risk of teratogenic and toxic effects of antimicrobials on the fetus is an
      additional cause of concern. In general, pregnant women are excluded from
      clinical trials and there is little pharmacokinetic information on the use and
      proper dosing of antimicrobials in this population. Although most antimicrobials
      can cross the placental blood barrier, data on the potential teratogenic effects,
      and fetal and neonatal toxicity caused by antimicrobials are also limited and of
      varying reliability. This article reviews the available evidence with the
      greatest clinical relevance regarding the pharmacology of different antibiotic,
      antifungal, antiviral, and antiparasitic agents in pregnancy, with particular
      focus on data related to fetal toxicity.

PMID- 19850376
TI  - Assessment of the putative binding conformation of a pyrazolopyridine class of
      inhibitors of MAPKAPK2 using computational studies.
AB  - The Ser/Thr protein kinase MAPKAP kinase2 (MAPKAPK2 or MK2) plays an important
      role in inflammation. A comparison of several crystal structures of MK2 shows
      that differences in active and inactive conformations result in large part from
      structural variations within the conformations of the glycine rich loop (p-loop)
      regions. We propose the most preferred binding conformation of two classes of MK2
      inhibitors and suggest plausible critical interactions with active site residues.
      The predicted binding conformations of the two classes of MK2 inhibitors depend
      upon their orientation in the active site and activities were well correlated
      with the sum of D and G scores. A qualitative relationship between the sum of D
      and G scores and the measured activities can be demonstrated.

PMID- 19850377
TI  - Novel three-component domino reactions of ketones, isatin and amino acids:
      synthesis and discovery of antimycobacterial activity of highly functionalised
      novel dispiropyrrolidines.
AB  - One-pot three-component domino reactions of cyclic mono ketones, isatin and
      sarcosine/phenylglycine furnishing highly functionalised dispiropyrrolidines in
      moderate yields are described. The reaction when performed with cyclic amino
      acid, proline resulted in the dimerization of azomethine ylides. These compounds
      have been screened for their in vitro activity against Mycobacterium tuberculosis
      H37Rv (MTB) using agar dilution method. Among thirty eight compounds screened, 1
      methylpyrrolo(spiro[2.3']-5-bromooxindole)spiro[3.2'']-1''-nitrosotetrahydro
      4''(1H)-pyridinone (4t) was found to be the most active with MIC of 1.98 microM
      against MTB and was 3.86 and 25.64 times more potent than the standard first line
      TB drugs, ethambutol and pyrazinamide respectively.

PMID- 19850378
TI  - Duplex in the assessment of the free radial forearm flaps: Is it time to change
      practice?
AB  - Radial forearm free flaps (RFFFs) are safe, but critical ischaemia of the hand
      has been described and is catastrophic. Every effort should therefore be made to
      improve the safety margin even further. Colour flow duplex ultrasound (US) is a
      simple, non-invasive and effective assessment tool. We compared it with Allen's
      test to identify serious vascular anomalies. We studied 121 patients who were
      listed to have a RFFF harvested, all of whom had both duplex US assessment and
      Allen's testing of the selected arm. The significance of differences in
      proportions was assessed using McNemar's test. Five of the 121 patients had an
      alternative flap selected as a consequence of the duplex assessment. A single
      flap failed. There were no ischaemic vascular complications that affected the
      hand.

PMID- 19850379
TI  - Double vascular anastomosis in the neck for reliable free jejunal transfer.
AB  - To reduce the possibility of necrosis in free jejunal transfer after total
      pharyngolaryngo-oesophagectomy, we made a second set of arterial and venous
      anastomoses in addition to the usual cervical arterial and venous anastomoses. To
      obtain two different arterial flows (carotid and subclavian systems), the
      recipient arteries were the superior thyroid and the transverse cervical. For
      venous flow, the internal and external jugular veins were used. All flaps
      survived. This procedure, which is limited to the already dissected neck with no
      procedures in other areas, is less invasive than others. Its advantages are that
      when one vessel has thrombosed the other vessel functions as a safety valve, and
      the greater pliability of the vascular pedicles makes it easier to reach the
      recipient vessels. Because this method is theoretically safe and results in less
      possibility of losing a flap when the anastomosis is unreliable, the double
      pedicled transfer can be an option for safer free jejunal transfer.

PMID- 19850380
TI  - A brief account of the life of Rene Le Fort.
AB  - In 1901, Rene Le Fort conducted some of the most infamous experiments known to
      maxillofacial surgery. He was an interesting and highly accomplished man with
      experience in many fields of surgery. We continue to use much of his research
      today despite many advances in medicine, yet we know little about the man
      himself.The aim of this short paper is to introduce you to Rene Le Fort and to
      describe the highlights of his experiments, which gave rise to a system of
      classifying facial fractures.

PMID- 19850381
TI  - Development of in-house rapid manufacturing of three-dimensional models in
      maxillofacial surgery.

PMID- 19850382
TI  - Endoscopically assisted treatment of condylar fractures--experiences following an
      educational course.
AB  - The main methods of managing condylar fractures are non-operative; closed
      reduction and maxillomandibular fixation; and open reduction and internal
      fixation. Endoscopically assisted reduction and fixation, although a recognised
      method, is not commonly used. As with all new techniques, training must be
      available to enable surgeons to gain experience and achieve competence. We
      surveyed consultant maxillofacial surgeons who attended a structured educational
      course with practical experience in the techniques of endoscopically assisted
      reduction and fixation of condylar fractures, with the aim of establishing the
      value of such a course, and the subsequent clinical experience of those surgeons
      with this new technique. The results indicated that over a quarter of all
      surgeons had already used this method of repair after attending the course.

PMID- 19850383
TI  - Quantifying scapula orientation and its influence on maximal hand force
      capability and shoulder muscle activity.
AB  - BACKGROUND: Non-neutral scapular orientations are often implicated as potential
      causes of shoulder pathologies. However, their specific influence on shoulder
      functional capabilities is largely unknown. This study objectively measured
      scapular orientation and quantified its influence on shoulder muscle activity
      levels and hand force capabilities during vertical and horizontal manual
      exertions. METHODS: Ten healthy male university students performed 24 exertions
      in combinations of scapular orientation (protracted, neutral and retracted),
      exertion direction (up, down, medial, lateral) and intensity (maximal or 40N).
      Scapular orientation was quantified using an acromion marker cluster method. An
      orientation by intensity repeated measures ANOVA identified differences in
      quantified scapular orientation. A two-way multivariate ANOVA identified the
      influence of scapular orientation and hand force direction on muscle activity and
      hand force capability. FINDINGS: Participants assumed consistent retracted,
      neutral, and protracted scapular orientations during exertions, and these three
      orientations were different from each other (F(2,99)=158.57; P-value: 0.0001).
      Scapular orientation and exertion direction influenced muscle recruitment almost
      universally (P-value: 0.05). Scapular orientation did not influence hand force
      capability (F(2,99)=1.34; P-value: 0.05), but a hand force direction effect on
      force existed (F(3,99)=144.19; P-value: 0.0001). INTERPRETATION: These findings
      support recommendations of health practitioners who advocate neutral scapular
      orientations to reduce injury risk, as a neutral orientation achieved a balanced
      overall muscle use pattern between retraction and protraction. Also, lowered
      muscle activity and higher maximal forces suggest that downward exertion forces
      may be preferable when possible.

PMID- 19850384
TI  - Ozone fumigation (twice ambient) reduces leaf infestation following natural and
      artificial inoculation by the endophytic fungus Apiognomonia errabunda of adult
      European beech trees.
AB  - In 2006, a controlled infection study was performed in the 'Kranzberger Forst' to
      address the following questions: (1) Will massive artificial inoculation with
      Apiognomonia errabunda override the previously observed inhibitory effect of
      chronic ozone? (2) Can biochemical or molecular markers be detected to account
      for the action of ozone? To this end six adult beech trees were chosen, three
      ozone fumigated (2x ozone) and three control trees (ambient = 1x ozone). Spore
      sprayed branches of sun and shade crown positions of each of the trees, and
      uninoculated control branches, were enclosed in 100-L plastic bags for one night
      to facilitate infection initiation. Samples were taken within a five-week period
      after inoculation. A. errabunda infestation levels quantified by real-time PCR
      increased in leaves that were not fumigated with additional ozone. Cell wall
      components and ACC (ethylene precursor 1-amino cyclopropane-1-carboxylic acid)
      increased upon ozone fumigation and may in part lead to the repression of fungal
      infection.

PMID- 19850385
TI  - Variation in immune function, body condition, and feather corticosterone in
      nestling tree swallows (Tachycineta bicolor) on reclaimed wetlands in the
      Athabasca oil sands, Alberta, Canada.
AB  - In the Athabasca oil sands region of northern Alberta, mining companies are
      evaluating reclamation using constructed wetlands for integration of tailings.
      From May to July 2008, reproductive performance of 40 breeding pairs of tree
      swallows (Tachycineta bicolor), plus growth and survival of nestlings, was
      measured on three reclaimed wetlands on two oil sands leases. A subset of
      nestlings was examined for i) feather corticosterone levels, ii) delayed-type
      hypersensitivity response, and iii) innate immune function. Nestlings on one of
      two wetlands created with oil sands process affected material (OSPM) were heavier
      and had greater wing-lengths, and mounted a stronger delayed-type
      hypersensitivity response compared those on the reference wetland. Corticosterone
      was significantly higher in male nestlings on one of two OSPM-containing wetland
      compared to the reference wetland. Body condition of 12-day-old female nestlings
      was inversely related to feather corticosterone. Under ideal weather conditions,
      reclaimed wetlands can support healthy populations of aerially-insectivorous
      birds.

PMID- 19850386
TI  - Permanent hearing loss with iopamidol following aortic angiography in a
      hemodialysis patient: a case report and review of the literature.
AB  - Nonionic low-osmolar contrast agents are considered safe for intravenous or intra
      arterial administration and are used widely in the general population, as well as
      in patients on hemodialysis therapy. There are data limited to case reports for
      contrast-induced hearing loss; however, the ototoxicity induced by contrast
      agents in patients with chronic kidney disease has never been described. We
      report a case of permanent sensorineural deafness after abdominal aortic
      angiography with iopamidol in a woman with end-stage renal disease on
      hemodialysis therapy and review the literature relating to contrast use with the
      development of hearing impairment.

PMID- 19850387
TI  - Plasma cell dyscrasia causing light chain tubulopathy without Fanconi syndrome.

PMID- 19850388
TI  - Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and
      prognosis in acute kidney injury: a systematic review and meta-analysis.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a
      promising biomarker for the early diagnosis of acute kidney injury (AKI);
      however, a wide range in its predictive value has been reported. STUDY DESIGN:
      Meta-analysis of diagnostic test studies using custom-made standardized data
      sheets sent to each author. SETTING & POPULATION: Different clinical settings of
      AKI. SELECTION CRITERIA FOR STUDIES: MEDLINE, EMBASE, and CENTRAL databases and
      congress abstracts were searched for studies reporting the value of NGAL to
      predict AKI. INDEX TESTS: Plasma/serum and urine NGAL within 6 hours from the
      time of insult (if known) or 24-48 hours before the diagnosis of AKI if the time
      of insult was not known. REFERENCE TESTS: The primary outcome was AKI, defined as
      an increase in serum creatinine level > 50% from baseline within 7 days or
      contrast-induced nephropathy (creatinine increase > 25% or concentration > 0.5
      mg/dL in adults or > 50% increase in children within 48 hours). Other outcomes
      predicted using NGAL were renal replacement therapy initiation and in-hospital
      mortality. RESULTS: Using a hierarchical bivariate generalized linear model to
      calculate the diagnostic odds ratio (DOR) and sample size-weighted area under the
      curve for the receiver-operating characteristic (AUC-ROC), we analyzed data from
      19 studies and 8 countries involving 2,538 patients, of whom 487 (19.2%)
      developed AKI. Overall, the DOR/AUC-ROC of NGAL to predict AKI was 18.6 (95% CI,
      9.0-38.1)/0.815 (95% CI, 0.732-0.892). The DOR/AUC-ROC when standardized
      platforms were used was 25.5 (95% CI, 8.9-72.8)/0.830 (95% CI, 0.741-0.918) with
      a cutoff value > 150 ng/mL for AKI compared with 16.7 (95% CI, 7.1-39.7)/0.732
      (95% CI, 0.656-0.830) for "research-based" NGAL assays. In cardiac surgery
      patients, the DOR/AUC-ROC of NGAL was 13.1 (95% CI, 5.7-34.8)/0.775 (95% CI,
      0.669-0.867); in critically ill patients, 10.0 (95% CI, 3.0-33.1)/0.728 (95% CI,
      0.615-0.834); and after contrast infusion, 92.0 (95% CI, 10.7-794.1)/0.894 (95%
      CI, 0.826-0.950). The diagnostic accuracy of plasma/serum NGAL (17.9 [95% CI, 6.0
      53.7]/0.775 [95% CI, 0.679-0.869]) was similar to that of urine NGAL (18.6 [95%
      CI, 7.2-48.4]/0.837 [95% CI, 0.762-0.906]). We identified age to be an effective
      modifier of NGAL value with better predictive ability in children (25.4 [95% CI,
      8.9-72.2]/0.930 [95% CI, 0.883-0.968]) compared with adults (10.6 [95% CI, 4.8
      23.4]/0.782 [95% CI, 0.689-0.872]). NGAL level was a useful prognostic tool with
      regard to the prediction of renal replacement therapy initiation (12.9 [95% CI,
      4.9-33.9]/0.782 [95% CI, 0.648-0.917]) and in-hospital mortality (8.8 [95% CI,
      1.9-40.8]/0.706 [95% CI, 0.530-0.747]). LIMITATIONS: Serum creatinine level was
      used for AKI definition. CONCLUSIONS: NGAL level appears to be of diagnostic and
      prognostic value for AKI.

PMID- 19850389
TI  - Screening for CKD and cardiovascular disease risk factors using mobile clinics in
      Jalisco, Mexico.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a major cause of morbidity and
      mortality in Mexico. However, many residents of underserved areas may be unaware
      that they potentially are affected. STUDY DESIGN: In an observational cross
      sectional study, we examined the diagnostic yield of screening for CKD and
      cardiovascular disease risk factors using mobile units that traveled to poor
      communities in Jalisco, Mexico. SETTING & PARTICIPANTS: We excluded individuals
      who were aware that they had CKD and those < 18 years of age. OUTCOMES:
      Glomerular filtration rate, cardiovascular risk. MEASUREMENTS: Demographic data,
      socioeconomic status, blood pressure, fasting glucose, and dipstick urinalysis.
      RESULTS: 3,734 participants; 29.3% men and mean age of 57.4 +/- 13.0 years. Most
      (99.7%) had no history of cardiovascular disease; however, 43.5% had a history of
      diabetes, 11.4% had dipstick-positive proteinuria, 62.0% had blood pressure in
      the hypertensive range, and 15.8% had an estimated glomerular filtration rate
      compatible with stages 3-5 CKD. In patients with no history of cardiovascular
      disease, proportions with predicted 5-year risks of new cardiovascular events
      <5%, 5%-10%, 10.1%-20%, 20.1%-30%, and >30% were 10.0%, 11.7%, 26.6%, 20.7%, and
      30.9%, respectively. Screening 18 participants aged < 40 years would be expected
      to detect 6 new cases of hypertension or 2 new cases of diabetes. LIMITATIONS:
      Data may not be generalizable to all low-income settings or other regions of
      Mexico. CONCLUSIONS: Impaired kidney function, proteinuria, and cardiovascular
      risk factors were detected frequently when mobile units were used to perform
      screening in poor areas of Jalisco, Mexico. This suggests that trials of targeted
      screening and intervention are feasible and warranted.

PMID- 19850390
TI  - Rebuilding health systems to improve health and promote statebuilding in post
      conflict countries: a theoretical framework and research agenda.
AB  - Violent conflicts claim lives, disrupt livelihoods, and halt delivery of
      essential services, such as health care and education. Health systems are often
      devastated in conflicts as health professionals flee, infrastructure is
      destroyed, and the supply of drugs and supplies is halted. We propose that early
      reconstruction of a functioning, equitable health system in countries recovering
      from conflict is an investment with a range of benefits for post-conflict
      countries. Building on the growing literature about health systems as social and
      political institutions, we elaborate a logic model that outlines how health
      systems may contribute not only to improved health status but also potentially to
      broader statebuilding and enhanced prospects for peace. Specifically, we propose
      that careful design of the core elements of the health system by national
      governments and their development partners can promote reliable provision of
      essential health services while demonstrating a commitment to equity,
      strengthening government accountability to citizens, and building the capacity of
      government to manage core social programs. We review the conceptual basis and
      extant empirical evidence for these mechanisms, identify knowledge gaps, and
      suggest a research agenda.

PMID- 19850391
TI  - Changes in the health burden of a national sample of children with asthma.
AB  - This paper focused on the extent to which factors that are modifiable by health
      policies or provider recommendations influenced the level and changes in the
      burden of childhood asthma. Demographic factors, access to health care services,
      and asthma control activities were posited to potentially influence the level and
      changes in health burden of children with asthma. The Medical Expenditure Panel
      Survey data from 1996-1999 on 3-11 year old U.S. children with asthma (N=784)
      were used. The findings of multilevel models of perceived burden indicated
      unfavorable trajectories among those families who had public health insurance.
      Asthma control activities were associated with favorable trajectories of both
      perceived and objectively measured burden. These findings emphasized the
      significance of asthma control and access to high quality and stable health care
      services as health policy targets.

PMID- 19850392
TI  - Prioritization and patients' rights: analysing the effect of a reform in the
      Norwegian hospital sector.
AB  - The right to equal treatment, irrespective of age, gender, ethnicity, socio
      economic status and place of residence, is an important principle for several
      health care systems. A reform of the Norwegian hospital sector of 2002 may be
      used as a relevant experiment for investigating whether centralization of
      ownership and management structures will lead to more equal prioritization
      practices over geographical regions. One concern was variation in waiting times
      across the country. The reform was followed up in subsequent years by some other
      policy initiatives that also aimed at reducing waiting lists. We measure
      prioritization practice by a method that takes departure in recommended maximum
      waiting times from medical guidelines. We merge the information from the
      guidelines with individual patient data on actual waiting times for the period
      1999-2005. This way we can monitor whether each patient in the available register
      of actual hospital visits has waited shorter or longer than what is considered
      medically acceptable by the guideline. The results indicate no equalization
      between the five new health regions, but we find evidence of more equal
      prioritization within four of the health regions. Our method of measuring
      prioritizations allows us to analyse how prioritization practice evolved over
      time after the reform, thus covering some further initiatives with the same
      objective. The results indicate that an observed reduction in waiting times after
      the reform have favoured patients of lower prioritization status, something we
      interpret as a general worsening of prioritization practices over time.

PMID- 19850393
TI  - How are organisational climate models and patient satisfaction related? A
      competing value framework approach.
AB  - Patient satisfaction has become an important indicator of process quality inside
      hospitals. Even so, the improvement of patient satisfaction cannot simply follow
      from the implementation of new incentives schemes and organisational
      arrangements; it also depends on hospitals' cultures and climates. This paper
      studies the impact of alternative models of organisational climate in hospital
      wards on patient satisfaction. Data gathered from seven public hospitals in Italy
      are used to explore this relationship. The theoretical approach adopted is the
      Competing Value Framework which classifies organisations according to their
      inward or outward focus and according to the importance assigned to control vs.
      flexibility. Results show that both a model stressing openness, change and
      innovation and a model emphasising cohesion and workers' morale are positively
      related to patient satisfaction, while a model based on managerial control is
      negatively associated with patient satisfaction.

PMID- 19850395
TI  - "Where is the sun" for hemi-neglect patients?
AB  - Human observers use prior constraints to disambiguate a scene; in particular,
      light is preferentially seen as coming from above but also slightly from the
      left. One explanation of this lateral bias could be a cerebral hemispheric
      difference. The aim of the present study was to determine the preferred light
      source position for neglect patients. For this purpose, we used the ambiguous
      shaded "Polo Mint" stimulus, a ring divided into eight equal sectors. All sectors
      but one were the same shape, convex or concave, as determined by the light source
      position. Participants had to report the side (left or right) of the odd sector
      or, in a separate experiment, to report its shape (convex or concave). Eight
      patients with spatial neglect (left neglect N=7, right neglect N=1) after a right
      or left temporo-parietal or thalamic lesion and 14 control participants ran the
      experiment. Left neglect patients showed a significantly different light bias
      from the bias observed for controls and for the right neglect patient (i.e., a
      reduction of the left bias or a right bias rather than a left bias). We conclude
      that some disabilities presented by patients with spatial neglect may be due to
      difficulties processing information that is not present in the visual field or
      imagined in the representational scene.

PMID- 19850394
TI  - Evidence for specificity of ERP abnormalities during response inhibition in ADHD
      children: a comparison with reading disorder children without ADHD.
AB  - Executive function and working memory deficits are not only present in ADHD, but
      also in reading disorder (RD). Here, high-density ERPs were recorded during the
      Stop Signal Task in 53 children and adolescents: An ADHD-combined type group, a
      group with RD, and a healthy control group. The ADHD-C group displayed unique
      abnormalities of the frontal N200. Both healthy controls and RD groups showed a
      success-related right frontal N200 modulation, which was absent in the ADHD
      group. Second, for Success Inhibition trials, the ADHD-C had smaller right
      frontal N200 waves relative to healthy controls, while the RD group did not. In
      contrast, NoGo-P3 abnormalities were present both in the ADHD-C and RD groups.
      Impaired early response inhibition mechanisms, indexed by the frontal N200,
      appear to be limited to ADHD-C. In contrast, deficits in later cognitive control
      and error monitoring mechanisms, indexed by the NoGo-P3, appear to be present in
      both conditions.

PMID- 19850396
TI  - Diseases from every organ system can raise cardiac troponin concentration.

PMID- 19850398
TI  - T cells in sputum of asthmatic patients are activated independently of disease
      severity or control.
AB  - BACKGROUND: T cells play an important role in bronchial asthma. Although airway
      CD4+ T cells have been extensively studied previously, there are hardly any
      studies relating CD8+ T cell activation and disease symptoms. OBJECTIVES: The aim
      of this study was to analyse the association between T cell activation in induced
      sputum T cells and asthma severity and control; and to evaluate T cell
      subpopulations in the same subgroups. METHODS: Fifty allergic asthmatic patients
      were recruited and lung function testing was performed. Airway cells were
      obtained by sputum induction via inhalation of hypertonic saline solution. CD3,
      CD4, CD8, CD28, CD25 and CD69 were studied by flow cytometry in whole induced
      sputum and peripheral blood cells. RESULTS: Total induced sputum T cells and CD8+
      T cells had a higher relative percentage of the activation markers CD25 and CD69
      in comparison with peripheral blood. In sputum, the relative percentage of CD25
      was higher in CD4+ T cells when compared to CD8+ T cells and the reverse was true
      regarding CD69. However, neither disease severity nor control were associated
      with the relative percentage of CD25 or CD69 expression on T cells in sputum.
      CONCLUSIONS: Both CD4+ and CD8+ T cells are activated in the lungs and peripheral
      blood of asthmatic patients. However, with the possible exception of CD69+ CD8+ T
      lymphocytes in the sputum, there is no association between T cell activation
      phenotype in the target organ and disease severity or control.

PMID- 19850399
TI  - Is there an association between wheezing and pneumonia?
AB  - OBJECTIVE: The aim of this study was to investigate whether there is a
      relationship in school aged children between wheezing and pneumonia prior,
      during, or following the pneumonia episode. PATIENTS-METHODS: One hundred and
      three children with community acquired pneumonia who were hospitalised were
      recruited along with 55 controls. RESULTS: During hospitalisation wheezing was
      audible in 11/103 (10.6%) patients with pneumonia and in none of the controls
      (p=0.009). Wheezing ever or asthma was elicited in 29/103(28%) patients with
      pneumonia and in 8/55 (14.5%) of the controls and this difference was not
      significant. Two years after the hospitalisation with pneumonia, wheezing
      episodes occurred in 12/103 with pneumonia and 1/55 of the controls (p=0.034).
      Among those who developed asthma following pneumonia 11/12 also had wheezing
      prior to pneumonia. CONCLUSION: There is an excess of wheezing prior, during, and
      after an episode of pneumonia in school aged children and therefore children with
      pneumonia should be followed up carefully.

PMID- 19850400
TI  - Perinatal outcome in singletons after modified natural cycle IVF and standard IVF
      with ovarian stimulation.
AB  - OBJECTIVE: Singletons born after IVF treatment are at risk for adverse pregnancy
      outcome, the cause of which is unknown. The aim of the present study was to
      investigate the influence of ovarian stimulation on perinatal outcome. STUDY
      DESIGN: In this single-centre retrospective study, perinatal outcome of singleton
      pregnancies resulting from IVF treatment with (n=106) and without ovarian
      stimulation (n=84) were compared. For IVF without ovarian stimulation, a modified
      natural cycle protocol was used. RESULTS: No differences were found in pregnancy
      duration, proportion of prematurity and proportion of low birth weight. Mean
      birth weight of modified natural cycle vs standard IVF singletons was 3485 (+/
      527) vs 3218 (+/-670)g; P=0.003. After adjustment for prognostic factors by
      linear regression analysis, the difference in birth weight remaining was 134 g;
      P=0.045. CONCLUSIONS: Birth weights of modified natural cycle IVF singletons
      found in this study are higher than standard IVF singletons, suggesting that
      ovarian stimulation may be a causative factor in the occurrence of low birth
      weight in standard IVF.

PMID- 19850401
TI  - Development of drinking water standards for perchlorate in the United States.
AB  - Perchlorate, an anion that originates as a contaminant in ground and surface
      waters, is both naturally occurring and manmade. Because of its toxicity, there
      has been increased interest in setting drinking water safety standards and in
      health effects when perchlorate is present at low (parts per billion (ppb))
      levels. In January 2009, the EPA issued a heath advisory to assist state and
      local officials in addressing local contamination of perchlorate in drinking
      water. The interim health advisory level of 15 micrograms per liter (microg/L),
      or ppb, is based on the reference dose recommended by the National Research
      Council (NRC) of the National Academy of Sciences (NAS). This paper describes
      scope and extent of contaminant issues and a legal process of setting standards
      for perchlorate concentration in drinking water in the United States of America.

PMID- 19850402
TI  - Reducing discards of fish at sea: a review of European pilot projects.
AB  - This paper is about improving the viability of discard-reduction pilot projects.
      One way to address the problem of wasteful discarding of fish at sea is to
      initiate pilot projects to trial potential solutions, such as selective gear,
      area closures, discard bans and data enhancement, which could subsequently be
      adopted by the fishing industry, either voluntarily or through regulation.
      However, such pilot projects are often difficult both to set up and to sustain
      through to completion and implementation. This study reviewed 15 discard-related
      pilot projects to find out what were the most important determinants of their
      success or lack of it, and to recommend ways in which the prospects of future
      pilots could be improved. The review identifies the seven most important factors
      associated with the viability of the pilot projects - fisheries crises;
      incentivization; funding; expertise; leadership; and enforcement - and shows how
      fisheries regulators could take steps to reinforce these factors - by faster
      responses to crises; more incentives and funding; greater use of fishers'
      knowledge and leadership; and better enforcement mechanisms.

PMID- 19850403
TI  - Investigation of sorption/desorption equilibria of heavy metal ions on/from
      quartz using rhamnolipid biosurfactant.
AB  - In the present study, the sorption characteristics of Cd(II) and Zn(II) ions on
      quartz, a representative soil-component, and the desorption of these metal ions
      from quartz using rhamnolipid biosurfactant were investigated. In the first part
      of the studies, the effects of initial metal ion concentration and pH on sorption
      of Cd(II) and Zn(II) ions by a fixed amount of quartz (1.5g) were studied in
      laboratory batch mode. The equilibrium sorption capacity for Cd(II) and Zn(II)
      ions was measured and the best correlation between experimental and model
      predicted equilibrium uptake was obtained using the Freundlich model. Although
      investigations on the desorption of heavy metal ions from the main soil
      components are crucial to better understand the mobility and bioavailability of
      metals in the environment, studies on the description of desorption equilibrium
      were performed rarely. In the second part, the desorption of Cd(II) and Zn(II)
      from quartz using rhamnolipid biosurfactant was investigated as a function of pH,
      rhamnolipid concentration, and the amounts of sorbed Cd(II) and Zn(II) ions by
      quartz. The Freundlich model was also well fitted to the obtained desorption
      isotherms. Several indexes were calculated based on the differences of the
      quantity of Cd-Zn sorbed and desorbed. A desorption hysteresis (irreversibility)
      index based on the Freundlich exponent, concentration-dependent metal
      distribution coefficients, and the irreversibility index based on the metal
      distribution coefficient were used to quantify hysteretic behavior observed in
      the systems.

PMID- 19850404
TI  - The impact of fusion on adjacent levels in cervical spine injuries: Is it really
      important?
AB  - OBJECTIVE: Although the literature on degenerative disease of the cervical spine
      contains numerous articles studying the changes on levels adjacent to a fusion,
      there exist very few such studies concerning cervical spine stabilization for
      trauma. METHODS: Over a 16-year period (1989-2005), one hundred and twelve
      patients underwent stabilization of the lower cervical spine (C3-T1) for subaxial
      cervical spine injuries, either with an anterior or posterior procedure, or both.
      Eighty-one patients with adequate follow-up were included in the study and 3
      groups were identified: Group A, consisting of 8 patients who underwent anterior
      stabilization and developed Adjacent Level Ossification Development (ALOD), Group
      B, comprising 53 patients who were anteriorly plated but who did not develop ALOD
      and Group C, comprising 20 patients who received posterior stabilization.
      RESULTS: Eight out of 61 patients (13.1%) who were anteriorly operated developed
      ALOD in 11 adjacent levels (Group A). Severe (grade 3) ossification was noted in
      6/8 patients at the cranial adjacent level, and in 2/8 patients at the caudal
      one. Three out of 8 patients presented with early ALOD at 3, 4 and 18 months
      respectively. Despite the radiographic abnormalities showing ossification, all
      the patients had an uncomplicated course without symptoms. All the radiographs of
      Group B and Group C patients demonstrated grade 0 ossification for both the
      cranial and caudal adjacent levels. CONCLUSION: Adjacent-level ossification in
      cervical spine injuries may appear very early in the postoperative period and it
      can have a different course than in the degenerative disc disease population, at
      least in some patients. The first cephalad level adjacent to a fusion appears to
      be at greater risk. However, even when ALOD is evident radiographically, it very
      rarely produces any symptoms.

PMID- 19850405
TI  - Geldanamycin and its anti-cancer activities.
AB  - Geldanamycin is a benzoquinone ansamycin antibiotic that manifests anti-cancer
      activity through the inhibition of HSP90-chaperone function. The HSP90 molecular
      chaperone is expressed at high levels in a wide variety of human cancers
      including melanoma, leukemia, and cancers in colon, prostate, lung, and breast.
      In cancer cells dependent upon mutated and/or over-expressed oncogene proteins,
      HSP90 is thought to have a critical role in regulating the stability, folding,
      and activity of HSP90-associated proteins, so-called "client proteins". These
      client proteins include the growth-stimulating proteins and kinases that support
      malignant transformation. Recently, oncogenic activating BRAF mutants have been
      identified in variety of cancers where constitutive activation of the MEK/ERK
      MAPK signaling pathway is the key for tumorigenesis, and they have been shown to
      be client proteins for HSP90. Accordingly, HSP90 inhibition can suppress certain
      cancer-causing client proteins and therefore represents an important therapeutic
      target. The molecular mechanism underlying the anti-cancer effect of HSP90
      inhibition is complicated. Geldanamycin and its derivatives have been shown to
      induce the depletion of mutationally-activated BRAF through several mechanisms.
      In this review, we will describe the HSP90-inhibitory mechanism, focusing on
      recent progress in understanding HSP90 chaperone structure-function
      relationships, the identification of new HSP90 client proteins and the
      development of HSP90 inhibitors for clinical applications.

PMID- 19850406
TI  - Formaldehyde and TVOC emission behaviors according to finishing treatment with
      surface materials using 20 L chamber and FLEC.
AB  - Formaldehyde and TVOC are emitted from wood-based panels that are made using wood
      particles, wood fiber, wood chips and formaldehyde-based resins. This study
      examined the formaldehyde and TVOC emission behavior of medium density fiberboard
      (MDF) overlaid with three types of uncoated lignocellulosic surface materials
      (oak decorative veneer, low pressure melamine impregnated paper and high pressure
      melamine impregnated paper) and four types of coated surface materials (coated
      paper, two types of finishing foils, and PVC) using the Field and Laboratory
      Emission Cell (FLEC) method and a 20 L small chamber method. The uncoated
      lignocellulosic surface materials exhibited lower formaldehyde and TVOC emission
      levels. The coated surface materials did not show reduced TVOC emissions but the
      formaldehyde emission was reduced in the 20 L small chamber test. In the FLEC
      test, both the uncoated lignocellulosic surface materials and coated surface
      materials showed lower TVOC and formaldehyde emissions from MDF.

PMID- 19850407
TI  - Experimental investigation on drag effect of sprinkler spray to adjacent
      horizontal natural smoke venting.
AB  - Discharge rate of a horizontal adjacent smoke vent under sprinkler spray is
      experimentally investigated. Temperature of smoke layer and velocity of smoke
      venting were measured, under different sprinkler operating pressures and smoke
      venting areas. CO concentration at the smoke vent center and velocity of vent
      flow with fresh air outside were recorded in tests under different smoke venting
      conditions. Experimental results have shown that efficiency of smoke venting is
      controlled by a combination of smoke buoyancy and drag force of sprinkler spray.
      Only when buoyancy is greater than drag force the smoke could be extracted by
      venting. Velocity of smoke venting has shown to decrease as the operating
      pressure increases. Smoke venting logging, which represents the failure of smoke
      venting, was experimentally found from certain operating pressure called initial
      logging pressure. The CO concentration was found to increase after sprinkler was
      operated as the smoke is constrained in the spray region with horizontal momentum
      decreased. Negative pressure difference is caused at the vent when there is smoke
      venting logging, which might practically bring the exterior fresh air into the
      fire building. Additionally, experiments results have shown that the venting area
      has little influence on smoke flow under smoke venting logging.

PMID- 19850408
TI  - Effects of titania nanoparticles on phosphorus fractions and its release in
      resuspended sediments under UV irradiation.
AB  - Little is known about the effects of nano-TiO(2) on the transformation and
      transport of phosphorus (P) in resuspended sediments. Chemical sequential
      extraction was used to investigate P fractions and its release in resuspended
      sediments under the influence of nano-TiO(2) and UV irradiation. The results
      showed that the contents of sediment P in all fractions decreased with increasing
      nano-TiO(2) concentration in UV irradiation, while increased in the dark
      controls. Furthermore, P release from all fractions was greater in UV irradiation
      than in the controls. Elevated concentrations (10-50 mg L(-1)) of nano-TiO(2) in
      UV irradiation significantly facilitated the release of P from organic and Fe
      oxide fractions, possibly resulting from the partial photo-degradation of organic
      matter and photochemical transformation of Fe oxides. Apparently, nano-TiO(2) in
      UV irradiation did not immobilize the loosely sorbed P and reductant soluble P
      release from the resuspended sediments, possible because (1) some of P released
      from those fractions were refurnished by the P released from OM; (2)
      photocatalysis of nano-TiO(2) reduced binding capacity of the resuspended
      sediments. Our results suggest that the photocatalysis of nano-TiO(2) may offer
      the potential to regulate the transformation and transport of sediment P in the
      aquatic environment.

PMID- 19850409
TI  - Preparation of dye waste-barium sulfate hybrid adsorbent and application in
      organic wastewater treatment.
AB  - A new hybrid material was developed by the template-free hybridization of weak
      acidic pink red B (APRB, C.I. 18073) with BaSO(4). The composition and structure
      of the material were determined and characterized. In contrast to conventional
      sorbents, the hybrid material has a specific surface area of 0.89 m(2)/g, but it
      contains lots of negative charges and lipophilic groups as the basis of specific
      adsorption. The efficient removal of cationic dyes and persistent organic
      pollutants (POPs) indicates that it has an improved adsorption capacity and
      selectivity with a short removal time less than 2 min; while the hybrid sorbents
      fit the Langmuir isotherm model, and follow the octanol-water partition law.
      Instead of using APRB reagent, an APRB-producing wastewater was reused to prepare
      the cost-effective sorbent, and the equilibrium adsorption capacities of which
      reached 222 and 160 mg/g for EV and BPR, respectively. The sorbents was then used
      to treat three wastewater samples with satisfactory results of over 97%
      decolonization and 88% COD-decreasing. In addition, the hybrid sorbent was
      regenerated from sludge over five cycles, and its adsorption capacity was not
      appreciably changed. This work has developed a simple and eco-friendly method for
      synthesizing a practical and efficient sorbent.

PMID- 19850410
TI  - Investigation on the photocatalytic degradation of pyrene on soil surfaces using
      nanometer anatase TiO2 under UV irradiation.
AB  - Photocatalytic degradation of pyrene on soil surfaces was investigated in the
      presence of nanometer anatase TiO(2) under a variety of conditions. After being
      spiked with pyrene, soil samples loaded with different amounts of TiO(2) (0%, 1%,
      2%, 3%, and 4%, w/w) were exposed to UV irradiation for 25h. The results
      indicated that the photocatalytic degradation of pyrene followed pseudo-first
      order kinetics. TiO(2) accelerated the degradation of pyrene generally as
      indicated by the half-life reduction from 45.90 to 31.36h, corresponding to the
      TiO(2) amounts from 0% to 4%, respectively. The effects of H(2)O(2), light
      intensity and humic acids on the degradation of pyrene were also investigated.
      The degradation of pyrene increased along with increasing the concentration of
      H(2)O(2), light intensity and the concentration of humic acids. All results
      indicated that the photocatalytic method in the presence of nanometer anatase
      TiO(2) was an advisable choice for the treatments of PAHs polluted soil in the
      future.

PMID- 19850411
TI  - Valorization of lignite combustion residues and ferroalumina in the production of
      aggregates.
AB  - The present research study investigates the synergy of industrial solid by
      products from lignite combustion (fly ash and bottom ash) and aluminum production
      (ferroalumina) in the production of lightweight aggregates (LWA). The process
      consists of two stages, pelletization and sintering. Bottom ash (BA) is used as
      the principal raw material in mixtures while ferroalumina (FAL) is added in lower
      percentages (5-30 wt%). BA carbon content is used as the fuel of sintering
      process in high temperatures, around 1250 degrees C, and gas generation is
      responsible for porous structure formation. Physical properties such as porosity,
      water absorption and bulk density, of sintering products are measured. Increase
      of FAL percentage in sintering mixtures results in decrease of porosity from 61%
      to 35% and of water absorption from 61% to 21% and in increase of bulk density
      from 1.02 g/cm(3) to 1.80 g/cm(3) of the produced aggregates. Aggregates produced
      by FAL addition up to 20 wt% are characterized as LWA. Aggregates formed are used
      in the production of concrete specimens. Compressive strength of concrete
      increases by increasing FAL addition in aggregates from 5 wt% to 15 wt% (highest
      strength value), while decrease by increasing FAL addition from 20 wt% to 30 wt%.
      FAL addition in lignite ashes sintering mixtures (up to 15 wt%) is considered as
      an important parameter for enhancing aggregates strength.

PMID- 19850412
TI  - Effects of fecal collection and storage factors on strongylid egg counts in
      horses.
AB  - Fecal analyses are becoming increasingly important for equine establishments as a
      means of parasite surveillance and detection of anthelmintic resistance. Although
      several studies have evaluated various egg counting techniques, little is known
      about the quantitative effects of pre-analytic factors such as collection and
      storage of fecal samples. This study evaluated the effects of storage
      temperature, storage time and airtight versus open-air storage on fecal egg
      counts. The experimental protocols were replicated in two study locations:
      Copenhagen, Denmark and Athens, Georgia, USA. In both locations, the experiment
      was repeated three times, and five repeated egg counts were performed at each
      time point of analysis. In experiment A, feces were collected rectally and stored
      airtight at freezer (-10 to -18 degrees C), refrigerator (4 degrees C), room (18
      24 degrees C), or incubator (37-38 degrees C) temperatures. Egg counts were
      performed after 0, 6, 12, 24, 48, and 120h of storage. In experiment B, feces
      were collected rectally and stored airtight or in the open air in the horse barn
      for up to 24h. Egg counts were performed after 0, 3, 6, 12, and 24h of storage.
      In experiment A at both locations, samples kept in the refrigerator showed no
      decline in egg counts, whereas storage in the freezer and incubator led to
      significantly declining egg numbers during the study. In contrast, storage at
      room temperature yielded marked differences between the two study locations: egg
      counts remained stable in the U.S. study, whereas the Danish study revealed a
      significant decline after 24h. In experiment B, the Danish study showed no
      differences between airtight and open-air storage and no changes over time, while
      the U.S. study found a significant decline for open-air storage after 12h. This
      difference was attributed to the different barn temperatures in the two studies.
      To our knowledge, this is the first study to evaluate the pre-analytic factors
      affecting egg counts in horses using an experimental protocol replicated in two
      contrasting geographic and climatic locations. Our results demonstrate that
      refrigeration is the best method for storage of fecal samples intended for egg
      count analysis, but that accurate results can be derived from fecal samples
      collected from the ground within 12h of passage.

PMID- 19850413
TI  - In silico predicted conserved B-cell epitopes in the merozoite surface antigen-2
      family of B. bovis are neutralization sensitive.
AB  - The merozoite surface antigens MSA-2 of Babesia bovis constitute a family of
      polymorphic GPI-anchored glycoproteins located at the parasite cell surface, that
      contain neutralization-sensitive B-cell epitopes. These are therefore putative
      vaccine candidates for bovine babesiosis. It was previously shown that (i) the
      MSA-2 antigens of the biologically cloned Mo7 strain are encoded by four tandemly
      organized genes: msa-2a(1), a(2), b and c, and (ii) at least one allele of each
      of these genes is present in the Argentine R1A strain with a moderate degree of
      polymorphism. The present work was aimed at defining neutralization-sensitive B
      cell epitopes in the MSA-2 family, that are conserved among different B. bovis
      geographical isolates. To this end, msa-2a, b and c alleles from different
      isolates from Argentina, USA and Mexico were amplified by PCR, cloned and
      sequenced. Bioinformatic analysis by ClustalW alignments and B-cell epitope
      prediction algorithms performed on these sequences allowed the identification of
      several regions containing putative conserved B-cell epitopes. Four peptides
      representing these regions: (KDYKTMVKFCN from msa-2a(1); YYKKHIS, from msa-2b;
      and THDALKAVKQLIKT and ELLKLLIEA from msa-2c) were chemically synthesized,
      conjugated to keyhole limpet hemocyanin and used to inoculate mice to obtain
      immune sera. Anti-peptide antibodies recognized B. bovis merozoite extracts in
      all cases in ELISA tests. In addition, these sera reacted with the surface of
      merozoites of an Argentine and a Mexican B. bovis strains in immunofluorescence
      assays, and sera against two of the selected peptides inhibited invasion of
      erythrocytes by in vitro cultured merozoites. Taken together, the results show
      that the peptide sequences selected by bioinformatic analysis represent expressed
      and geographically conserved B. bovis B-cell epitopes that might be strong
      candidates for development of subunit vaccines.

PMID- 19850414
TI  - Combination of cell culture and quantitative PCR (cc-qPCR) to assess
      disinfectants efficacy on Cryptosporidium oocysts under standardized conditions.
AB  - Oocysts of Cryptosporidium parvum are resistant to environmental conditions and
      many disinfectants. A combination of cell culture and quantitative real time PCR
      (cc-qPCR) is established for evaluation of anticoccidial disinfectants against C.
      parvum. C. parvum oocysts were treated with disinfectants, washed and oocysts
      were incubated with HCT-8 cell monolayers in the presence of excystation medium
      for 3h. Subsequently, unbound parasites were removed by washing with growing
      medium and the infected monolayers were further maintained in fresh growing
      medium for 48h. Genomic DNA was extracted from each sample and qPCR performed
      targeting a specific sequence of the 70kDa heat shock protein gene in order to
      quantify development. Treatment of oocysts with cresolic disinfectants
      demonstrated dose dependent reduction of viability of oocysts. More than 98%
      inactivations were recorded with at least 2% concentration of cresolic
      disinfectants after 2h of treatment. Bleach (sodium hypochlorite) at 6% solution
      induced 92.7% inactivation of C. parvum oocysts after 2h. Thermally treated
      oocysts (56 and 70 degrees C for 20min) demonstrated complete inactivation,
      whereas at 38 degrees C no inactivation was observed. Application of
      Neopredisan((R)) 135-1 and Aldecoc((R)) TGE (4% for 2h) as recommended according
      to the current guidelines stipulated by DVG (German Veterinary Society)
      consistently inactivated more than 99.5% of oocysts. The suggested cc-qPCR method
      appeared to be suited for standardized testing of inactivation measures,
      particularly for evaluation of chemical disinfectants and thus cc-qPCR is
      proposed as an alternative to the established chicken infectivity model for
      Eimeria tenella for testing anticoccidial disinfectants. A minimum inactivation
      of 99.5% in cc-qPCR model is claimed as a suitable threshold for certification of
      chemical products for disinfection of coccidia oocysts.

PMID- 19850415
TI  - Alcohol use disorders and acute alcohol use preceding suicide in China.
AB  - OBJECTIVES: Identify distinguishing characteristics of subgroups of suicides
      classified according to different patterns of alcohol use prior to death.
      METHODS: Three groups of suicide decedents from a representative sample of 454
      male suicides in China identified in a national psychological autopsy study were
      classified and compared: decedents with an alcohol use disorder during the year
      prior to death, those without an alcohol use disorder who used alcohol acutely at
      the time of suicide, and those with neither an alcohol use disorder nor acute
      use. RESULTS: Compared with suicides unrelated to alcohol, those with an alcohol
      use disorder were more likely to have made previous suicide attempts (adjusted
      OR, 95%CI=1.94, 1.07-3.53), and suicides with acute alcohol use were less likely
      to have poor overall functioning in the month before death (0.36, 0.20-0.63).
      CONCLUSIONS: The characteristics of male suicide decedents with an alcohol use
      disorder, using alcohol acutely but without an alcohol use disorder, and with no
      alcohol involvement are somewhat different, suggesting the potential value of
      tailored prevention strategies.

PMID- 19850416
TI  - Apnea: a new training method in sport?
AB  - The physiological responses to apnea training exhibited by elite breath-hold
      divers may contribute to improving sports performance. Breath-hold divers have
      shown reduced blood acidosis, oxidative stress and basal metabolic rate, and
      increased hematocrit, erythropoietin concentration, hemoglobin mass and lung
      volumes. We hypothesise that these adaptations contributed to long apnea
      durations and improve performance. These results suggest that apnea training may
      be an effective alternative to hypobaric or normobaric hypoxia to increase
      aerobic and/or anaerobic performance.

PMID- 19850417
TI  - Diabetes, diet and autonomic denervation.
AB  - Contemporary theories to explain the autoimmune aetiology of type 1 diabetes
      mellitus (T1DM) include the "hygiene", "accelerator" and "thrifty phenotype"
      hypotheses though none accounts for its natural history, or, epidemiology. Early
      onset, T1DM is much more common in Western countries and shares features of its
      epidemiology with other major childhood diseases. In the autonomic denervation
      view, early-onset, T1DM results from injury to autonomic nerves supplying the
      pancreas through persistent physical efforts during defaecation in infancy.
      Pancreatic denervation results in loss of islets of Langerhans and reduced
      insulin production that may present in infancy or later life. Early introduction
      of cows milk and solids to the infants' diet cause increased rates of bowel
      problems whereas exclusive breastfeeding in non-Western countries, protects the
      infant from both constipation and diarrhoea. Other important Western diseases may
      result from the varying effects of injuries to nerves at different sites in the
      autonomic nervous system.

PMID- 19850418
TI  - [Breast cancer screening imaging: what do we do].
AB  - The purpose of this review is to evaluate the value of different breast imaging
      technics and their place for individual and mass screening of breast cancer
      according to the randomized studies on digital mammography and ultrasound
      screening. Analogic and numerical mammograms are validated for screening of women
      aged from 50 and 74 years. The additional value of ultrasound is therefore proven
      when the increased risk is moderate. When risk is higher (genetic or familial),
      MRI is the method of choice associated with conventional imaging. Individual
      screening is recommended before 50 for women aged from 45 and 50 and for those
      over 74 using the same procedures as organized screening.

PMID- 19850419
TI  - Preface.

PMID- 19850420
TI  - RNA interference targeting nucleocapsid protein (C) inhibits classical swine
      fever virus replication in SK-6 cells.
AB  - The application of RNA interference (RNAi) strategy for controlling classical
      swine fever could become a promising alternative to the conventional eradication
      measures, as it was recently shown for foot-and-mouth disease (Chen et al.,
      2004), influenza (Ge et al., 2003), porcine reproductive and respiratory syndrome
      (He et al., 2007) and porcine transmissible gastroenteritis (Zhou et al., 2007).
      The use of synthetic siRNA which is corresponding to nucleotides 1130-1148 of the
      CSF virus strain Alfort, targeting the nucleocapsid protein (C) was investigated
      to show the inhibition of CSF virus replication. It could be shown that the virus
      titer of infected cells, which had been mock-transfected or transfected with
      control (non-silence) RNA were not affected. These data indicate that siRNA_253
      is able to inhibit viral replication.

PMID- 19850421
TI  - Transcriptional expression levels of chicken collectins are affected by avian
      influenza A virus inoculation.
AB  - Mammalian collectins have been found to play an important role in the defense
      against influenza A virus H9N2 inoculation, but for chicken collectins this has
      not yet been clarified. The aim of this study was to determine the effect of
      avian influenza A virus (AIV) inoculation on collectin gene expression in the
      respiratory tract of chickens and whether this was affected by age. For this
      purpose 1- and 4-week-old chickens were inoculated intratracheally with PBS or
      H9N2 AIV. Chickens were killed at 0, 8, 16 and 24h post-inoculation and trachea
      and lung were harvested for analysis. Viral RNA expression and mRNA expression of
      chicken collectins 1 and 2 (cCL-1 and cCL-2), chicken lung lectin (cLL) and
      chicken surfactant protein A (cSP-A) were determined using real-time quantitative
      RT-PCR. In lung, a decrease in mRNA expression of cCL-2, cLL and cSP-A after
      inoculation with H9N2 was seen in both 1- and 4-week-old birds, although at
      different time points, while in trachea changes were only seen in 4-week-old
      birds and expression was increased. Moreover, collectin expression correlated
      with viral RNA expression in lung of 1-week-old birds. These results suggest that
      both age and location in the respiratory tract affect changes in collectin mRNA
      expression after inoculation with H9N2 and indicate a possible role for
      collectins in the host response to AIV in the respiratory tract of chickens.

PMID- 19850422
TI  - Characterization of Mithun (Bos frontalis) ejaculates and fertility of
      cryopreserved sperm.
AB  - Technologies for conservation and propagation of genetic resources in the Mithun
      (Bos frontalis), a rare semi-wild bovine species of Southeast Asia. Successful
      cryopreservation of Mithun semen would provide a potential vehicle to address
      above issue. To date, information on characteristics of Mithun ejaculates is not
      available and there are no reports of birth of live offspring using cryopreserved
      Mithun semen collected using AV method. A study was therefore conducted to (i)
      characterize the Mithun ejaculate, (ii) investigate the effectiveness of Mithun
      sperm cryopreservation, and (iii) determine whether artificial insemination using
      frozen-thawed Mithun sperm can result in live offspring. Semen samples collected
      from eight fertile Mithun bulls were evaluated for colour, consistency, volume,
      concentration, mass activity and progressive motility. The freshly ejaculated
      sperm were also evaluated for morphological abnormalities, live sperm counts,
      acrosome integrity, membrane stability (hypo-osmotic swelling test; HOST) and DNA
      integrity. Semen samples of good quality were cryopreserved in liquid nitrogen
      using Tris-egg yolk-glycerol diluent. Post-thaw quality of the cryopreserved
      sperm in terms of progressive motility, morphological abnormalities, live sperm
      counts, acrosome integrity, membrane stability and DNA integrity were assessed.
      In addition, 16 Mithun cows at estrus were inseminated with frozen-thawed Mithun
      sperm. Following cryopreservation, the percentage of progressive motility (fresh
      versus frozen-thawed), live sperm counts, morphological abnormalities, acrosome
      integrity, membrane stability and DNA integrity were found to decrease (P<0.01)
      with a motility recovery rate of 74+/-9%. Mithun cows inseminated with
      cryopreserved sperm result 75% conception rate and all the conceived cows
      maintained full-term pregnancy with delivery of live calves.

PMID- 19850423
TI  - Multidrug poisoning involving nicotine and tramadol.
AB  - A fatal case of multidrug poisoning by tramadol and nicotine is reported.
      Tramadol is a centrally acting analgesic used in the treatment of moderate to
      severe acute or chronic pain. Nicotine, a lipid-soluble alkaloid, is one of the
      most readily available drugs in modern society. A 46-year-old man was found dead
      in his bed, and a suicide note was discovered near the body. He had 25
      transdermal nicotine patches attached to his thorax and abdomen. Two half emptied
      bottles were found on the bedside table; the toxicological examination revealed
      that they contained tobacco and nicotine as well as other drugs such as
      diphenhydramine. At autopsy, areas of fresh and old myocardial infarction as well
      as diffuse pulmonary congestion and edema were present. The tramadol
      concentration was 6.6 microg/mL in femoral venous blood, while levels of nicotine
      and its primary metabolite cotinine were determined to be 0.6 and 2.0 microg/mL
      in femoral venous blood. Based on these results, we determined the cause of death
      to be cardiorespiratory failure induced by the additive effects of tramadol and
      nicotine shortly after consumption.

PMID- 19850424
TI  - Sex determination using metacarpal biometric data from the Athens Collection.
AB  - Forensic anthropologists and bioarchaeologists usually determine sex by analyzing
      quantitative and qualitative characters of the human skeleton. In general, the
      pelvis and skull are the skeletal parts used most often, but in many cases these
      parts are missing or fragmentary. In such circumstances, it is necessary to use
      techniques based on other skeletal elements. The primary aim of this work is to
      determine whether metacarpals can be used for the determination of sex
      specifically in a Greek population. A secondary step is to describe and develop
      linear discriminant function equations for sex determination based on a
      contemporary Greek population using metacarpal biometric data. The skeletal
      sample of the modern Greeks is housed at the National and Kapodistrian University
      of Athens (NKUA) is comprised of 993 metacarpals (left and right), corresponding
      to 151 adult individuals (84 males and 67 females). The correct sex
      classification reached an accuracy of 83.7-88.1% for left and 83.8-89.7%, for
      right metacarpals. Our results suggest that metacarpals can be used for sexing in
      bioarchaeological, and forensic studies, in addition to other sex determination
      techniques.

PMID- 19850425
TI  - Raman spectroscopic signature of semen and its potential application to forensic
      body fluid identification.
AB  - A great potential of Raman spectroscopy for non-destructive, confirmatory
      identification of body fluids at the crime scene has been reported recently
      (Virkler and Lednev, Forensic Sci. Int. 2008). However, that analysis was carried
      out on only one sample of each body fluid and did not take into account any
      variations that might occur between different donors of the same fluid. This
      paper reports on the role of heterogeneity within a sample as well as among
      multiple donors for human semen. Near-infrared (NIR) Raman spectroscopy was used
      to measure spectra of pure dried human semen samples from multiple donors in a
      controlled laboratory environment. The major chemical components that contributed
      to the Raman spectrum of semen were determined and used to tentatively identify
      the principal spectral components. The issue of potential spectral variations
      that could arise between different donors of semen was also addressed. Advanced
      statistical analysis of spectra obtained from multiple spots on dry samples
      showed that dry semen is heterogeneous and its Raman spectra could be presented
      as a linear combination of a fluorescent background and three spectral
      components. The relative contribution of each of the three components varies with
      donor, so no single spectrum could effectively represent an experimental Raman
      spectrum of dry semen in a quantitative way. The combination of the three
      spectral components could be considered to be a spectroscopic signature for
      semen. This proof-of-concept approach shows the potential for Raman spectroscopy
      to identify an unknown substance to be semen during forensic analysis.

PMID- 19850426
TI  - Burow's solution-induced acute sensorineural hearing loss: report of two cases.
AB  - This is the report of rare cases to show the potential ototoxicity of Burow's
      solution in clinical use. We encountered two cases of acute sensorineural hearing
      loss occurring after the administration of 8% Burow's solution (pH 2.93) into the
      tympanic cavities. Prior to treatment, both cases presented with tympanic
      membrane perforations in the posterior and inferior portions and a small amount
      of serous discharge. Fortunately, hearing loss recovered almost completely except
      for high tones within a few weeks. These two case reports demonstrate that the
      ototoxicity of Burow's solution should be considered when it is used to treat
      otitis media accompanied by tympanic membrane perforation.

PMID- 19850427
TI  - Epileptic encephalopathy in children possibly related to immune-mediated
      pathogenesis.
AB  - Severe epilepsy in the paediatric population negatively influences neurological
      and cognitive development. Different etiological factors could be responsible of
      these severe epilepsies, and an early diagnosis could change, in some cases, the
      neurological and cognitive development. Immune mechanisms have been reported in
      epilepsy. Epilepsy has been associated with systemic lupus erythematosus, with
      the presence of anti-phospholipid antibodies (aPL), anti-cardiolipin antibodies,
      anti-nuclear antibodies, Beta2-glycoprotein antibodies, and anti-glutamic acid
      decarboxylase (anti-GAD) antibodies. CNS inflammation and markers of adaptive
      immunity have been, also, associated with some epileptic syndromes, such as West
      syndrome, temporal lobe epilepsy, febrile seizures, tonic-clonic seizures, and
      tuberous sclerosis. Inflammation and blood-brain barrier (BBB) disruption could
      be one of the mechanisms responsible for seizure recurrence. Recently clinical
      entities, characterized by severe epilepsy with a febrile, acute or sub-acute
      onset, sometimes associated with status epilepticus, followed by drug-resistant,
      partial epilepsy have been described. Some of these publications also suggested
      acronyms for the condition described: Acute Encephalitis with Refractory,
      Repetitive Partial Seizures (AERRPS) reported by Japanese authors, Devastating
      Epileptic Encephalopathy in School-aged Children (DESC) reported by French
      authors. Among children with acquired symptomatic severe epilepsy, we identified
      a group of previously normal children who had developed severe partial epilepsy
      after an acute/sub-acute illness resembling encephalitis. The etiological factors
      for those patients seems to remain unknown, and a possible immune-mediating or
      inflammatory process as pathogenesis of the disease could be hypothesized. More
      studies need to be addressed to finally define this peculiar epileptic entity.

PMID- 19850428
TI  - [Carbapenem use in severe infections].

PMID- 19850429
TI  - Applications of a planar electrochemiluminescence platform to support regulated
      studies of macromolecules: benefits and limitations in assay range.
AB  - Development and validation of ligand binding methods that can measure therapeutic
      antibodies (TA) accurately and precisely are essential for bioanalysis that
      supports regulated pharmacokinetic (PK) and toxicokinetic (TK) studies. Non-bead
      (planar) electrochemiluminescence (ECL) methods are known to have high
      sensitivity and a wide assay range and are therefore potentially useful in
      supporting research studies in the early phases of development as well as for
      diagnostic fields and multiplex biomarker applications. Here, we demonstrate the
      applications for using ECL for regulated studies associated with protein drug
      development. Three planar ECL methods were developed, validated, and implemented
      to quantify three different TAs to support PK/TK studies. An automated liquid
      handler was used for the preparation of standards, quality controls, and
      validation samples to minimize assay variability. Robustness and ruggedness were
      tested during pre-study validations. During method optimization, the potential
      assay ranges were 3 log orders. To improve assay accuracy and precision, assay
      ranges in all 3 methods were truncated by at least 50% at the upper end before
      proceeding to pre-study validations. All 3 methods had assay ranges of about 2
      logs during pre-study validations. The inter-assay accuracy and precision during
      pre-study validations were <6% and 8%, respectively. The total error of the
      assays was <15% for both in-study and pre-study validations in all 3 methods.
      With the incorporation of a robotic workstation we concluded that performance in
      all 3 planar ECL methods was extremely precise and accurate during pre-study and
      in-study validations, enabling >90% assay success during sample analyses.
      Although there were limitations in the assay ranges, the strength of this
      technology in assay accuracy, precision, and reproducibility can be beneficial
      for macromolecule analyses in support of PK and TK studies in a regulated
      environment.

PMID- 19850430
TI  - Extremely long time stability study of selected antibiotic standards.
AB  - A study was conducted to investigate the quality of reference substances which
      were produced long before the introduction of advanced analysis and purification
      techniques. The quality and antimicrobial activity of WHO and EP oxytetracycline,
      doxycycline, colistin and spiramycin reference standards were assessed. The
      oldest substance was stored for 54 years in a freezer. Assay and purity tests
      were conducted according to Ph. Eur. 6.0. Additionally, antibacterial activity
      was tested with the microbiological method according to Ph. Eur. 4.0 (agar
      diffusion method). The results of the study show that several of the tested
      substances remained stable for over 40 years and one for over 50 years of
      storage. In most cases, the determined potency is close to the declared one,
      regardless of the method used (HPLC or microbiological). Composition analysis of
      multi-substance antibiotics (colistin and spiramycin) showed important
      differences compared with new reference substances. Results also indicate that no
      excessive degradation occurred during the entire storage period and impurity
      levels have not changed significantly.

PMID- 19850431
TI  - HPLC analysis of mitoxantrone in mouse plasma and tissues: application in a
      pharmacokinetic study.
AB  - A simple, fast and economical HPLC assay for the determination of mitoxantrone in
      mouse plasma and tissue homogenates is described. Protein precipitation with
      sequential addition of sulfosalicylic acid and acetonitrile was used for sample
      preparation. The resolution of mitoxantrone and the I.S. were achieved by using
      acetonitrile and 10mM sodium phosphate buffer with 0.1% TEA. The separation was
      performed on a Nucleosil C18, 250mmx4mm I.D. column with UV detection at 610nm.
      The inter-day and intra-day precision and accuracy of quality control (QC)
      samples, evaluated both in plasma and tissue homogenates, were all within 15%.
      The lower limit of quantification (LLOQ) was 5ng/ml in plasma, 25ng/ml in liver
      homogenate and 12.5ng/ml in other tissue homogenates. This assay was successfully
      applied in a pharmacokinetic and tissue distribution study of mitoxantrone in
      mice.

PMID- 19850432
TI  - Discrimination of polysaccharides from traditional Chinese medicines using
      saccharide mapping--enzymatic digestion followed by chromatographic analysis.
AB  - Polysaccharides isolated from traditional Chinese medicines (TCMs) exhibit
      multiple pharmacological activities. However, quality control of polysaccharides
      is a challenge because of their complicate structure and macro-molecular mass. In
      this study, saccharide mapping based on specific enzymatic digestion of
      polysaccharides and chromatographic analysis was proposed to discriminate the
      polysaccharides from different TCMs. Endo-carbohydrase such as glucanase,
      arabinanase, xylanase, galactanase, cellulase, amylase and pectinase were used
      for enzymatic digestion of polysaccharides from 9 TCMs namely Panax ginseng, P.
      notoginseng, P. quinquefolium, Cordyceps sinensis, C. militaris, Ganoderma
      lucidum, G. sinense, Astragalus membranaceus and Angelica sinensis. By using high
      performance size exclusion chromatography (HPSEC) as well as derivatization with
      1-Phenyl-3-methyl-5-pyrazolone (PMP) and HPLC analysis, the enzymatic hydrolysis
      properties of polysaccharides and their saccharide mapping were determined. The
      polysaccharides from 9 TCMs were firstly successfully distinguished based on
      their characteristic saccharide maps, which is helpful to improve the quality
      control of polysaccharides.

PMID- 19850433
TI  - Improving the ex vivo stability of drug ester compounds in rat and dog serum:
      inhibition of the specific esterases and implications on their identity.
AB  - In drug development, it has been noticed that some drug compounds, especially
      esters, are unstable in serum samples ex vivo. This can lead to a substantial
      underestimation of the actual drug concentration. The rat and the dog,
      representing a rodent and non-rodent species, respectively, are widely used in
      preclinical studies. We studied the degradation of three structurally different
      drug esters in rat and dog serum. Moreover, the efficiency of selected enzyme
      inhibitors to prevent these degradations was investigated. Furthermore, we found
      indications of the identity of the drug-specific esterases by means of their
      inhibitor sensitivity as well as by protein purification and identification. The
      studied drugs were sagopilone, drospirenone, and methylprednisolone aceponate
      (MPA) all of which are used in (pre-)clinical drug development. The sagopilone
      cleaving esterases in rat serum were inhibited by serine hydrolase inhibitors. We
      partly purified these esterases resulting in an activity yield of 5% and a
      purification factor of 472. Using matrix-assisted laser desorption ionization
      (MALDI)-time of flight (TOF)-mass spectrometry (MS), the rat carboxylesterase
      isoenzyme ES-1 was identified in these fractions, thus pointing to its
      involvement in sagopilone cleavage. Drospirenone cleavage in rat serum was
      effected by butyrylcholinesterase (BChE) and paraoxonase 1 (PON1) as we deduced
      from the high efficacy of certain serine hydrolase and metallohydrolase
      inhibitors, respectively. Likewise, some inhibition characteristics implied that
      MPA was cleaved in rat serum by BChE and serine proteases. Partial purification
      of the MPA-specific esterases resulted in activity yields of 1-2%, exhibiting up
      to 10,000-fold purification. In dog serum, we found that sagopilone was not
      degraded which was in contrast to MPA and drospirenone. MPA degradation was
      mainly prevented by serine hydrolase inhibitors. We used a three-step
      purification to isolate the esterases cleaving MPA. This procedure resulted in an
      activity yield of 12% and 645-fold purification. By protein identification using
      liquid chromatography (LC)-electrospray ionization (ESI)-MS, we identified
      alpha(2)-macroglobulin (alpha(2)M) in the active fractions. We therefore assumed
      that serine hydrolases, probably butyrylcholinesterase, known to form
      esteratically active complexes with alpha(2)M, were responsible for MPA cleavage.
      In contrast, PON1 was assumed to be involved in drospirenone cleavage due to the
      high efficiency of metallohydrolase inhibitors. This indication was supported by
      the presence of PON1 in drospirenone-cleaving fractions as we found by affinity
      chromatography and Western immunoblotting for isolation and detection of PON1,
      respectively. The identity of the assumed cleaving enzymes remains, however, to
      be further studied. The inhibitors we found can serve as a tool for stabilizing
      drug ester compounds in biological samples ex vivo.

PMID- 19850434
TI  - Identification of adulterants in a Chinese herbal medicine by LC-HRMS and LC-MS
      SPE/NMR and comparative in vivo study with standards in a hypertensive rat model.
AB  - Based on anecdotal evidence of anti-hypertensive effect of Gold Nine Soft
      Capsules, an in vivo study of this complex Chinese "herbal-based" medicine was
      initiated. Dosage of the content of Gold Nine capsules in spontaneous
      hypertensive rats showed a remarkably good effect. This led to further
      investigation of the components of the preparation and eventual identification of
      three known anti-hypertensive drugs; amlodipine, indapamide and valsartan, which
      were not declared on the label. Compounds were rapidly identified using LC-HRMS
      and LC-MS-SPE/NMR, quantified by HPLC, and the in vivo activity of a combination
      of commercially purchased standards was shown to be equivalent to that of the
      capsule content. Adulteration of herbal remedies and dietary supplements with
      synthetic drugs is an increasing problem that may lead to serious adverse
      effects. LC-MS-SPE/NMR as a method for the rapid identification of such
      adulterants is highlighted in this case study.

PMID- 19850435
TI  - Health professionals' perceptions of intimate partner violence against women in
      Serbia: opportunities and barriers for response improvement.
AB  - OBJECTIVE: The aim of this study was to determine the perceptions and attitudes
      of health professionals toward violence against women in intimate relationships,
      and to discuss them as opportunities and barriers for improving health
      professionals' response. METHODS: Six focus groups were conducted with 71 health
      professionals employed in the public primary health care centers in Belgrade
      (Serbia). The data were analyzed according to the direct approach of the
      qualitative content analysis. RESULTS: Findings suggest that the majority of
      health professionals perceive IPV as an unjustifiable act. They showed an
      understanding for women; see their role as providing support to women and
      collaborating with other institutions. They are willing to help, but do not know
      how. However, some health professionals appeared to be judgmental in terms of
      what preceded violence, and would insist on extracting a woman's disclosure that
      violence had occurred. As barriers, they emphasized the lack of training and
      specific education on IPV, a weak support network, and overall social insecurity.
      CONCLUSION: There is a gap between health professionals' willingness to help and
      resources needed, along with prejudice and interrogative attitudes. Barriers
      appeared at individual, organizational and societal levels. PRACTICE
      IMPLICATIONS: Proper education and protocols are priorities in strengthening
      health professionals' response to IPV.

PMID- 19850436
TI  - Discussing prognosis with terminally ill cancer patients and relatives: a survey
      of physicians' intentions in seven countries.
AB  - OBJECTIVE: To determine the extent to which physicians in different countries
      intend to inform terminal patients and relatives about prognosis, and to identify
      physician characteristics associated with an active approach to such discussions.
      METHODS: In the context of a European research project, a study on disclosing
      prognosis was conducted in seven countries. A written questionnaire with
      questions regarding hypothetical cases and actual practices was sent to
      physicians from specialties involved in the care of dying patients. RESULTS:
      10,139 questionnaires were studied. The response rate was greater than 50% in all
      countries except Italy (39%). The percentage of physicians who indicated that
      they would actively inform competent patients of their prognosis varied between
      countries from 52% in Italy to 99% in Sweden. For informing relatives of
      incompetent patients, rates were higher, ranging from 86% in Denmark to 98% in
      Australia. Younger physician age and training in palliative care were associated
      with an active intention to discuss prognosis. CONCLUSION: Physicians' intentions
      to discuss prognosis with patients and families vary largely across countries.
      Physician age and training in palliative care may also affect intentions.
      PRACTICE IMPLICATIONS: Continuing training should focus on improving physicians'
      ability to communicate responsibly about prognosis with patients and families.

PMID- 19850438
TI  - Implementing decision and communication aids to facilitate patient-centered care
      in breast cancer: a case study.
AB  - OBJECTIVE: Decision Services (DS) provide support for breast cancer patients at
      the University of California, San Francisco to help ensure patient-centered care.
      METHODS: We examined a case study to explore whether our program practices
      matched our program theory, and what the patient in the case thought was
      effective and ineffective about our decision support interventions. RESULTS: The
      patient relied on a decision aid to educate her husband about her condition; felt
      that her question list contributed to a productive and efficient consultation
      with her oncologist; credited an audio-recording with helping her remember to
      follow-up with a genetic counselor; and reviewed the consultation summary 30 days
      into treatment in order to reflect on her decision. The patient rated the
      interventions highly on surveys, and experienced desirable reductions in
      decisional conflict, and improvements in knowledge. However, the question
      prompting intervention was associated with a small decrease in self-efficacy, and
      the patient criticized the decision aid for omitting mention of a prognostic
      test. CONCLUSION: This case illustrates how decision support interventions can be
      deployed to promote patient-centered care. PRACTICE IMPLICATIONS: Breast care
      centers should consider distributing decision aids and assisting patients in
      listing questions, recording consultations, and obtaining written consultation
      summaries.

PMID- 19850437
TI  - Reconsidering the team concept: educational implications for patient-centered
      cancer care.
AB  - Patient-centered cancer care has become a priority in the oncology field.
      Increasing efforts to train oncologists in communication skills have led to a
      growing literature on patient-centered cancer education. In addition, systems
      approaches have led to an increased emphasis on the concept of teams as an
      organizing framework for cancer care. In this essay, we examine issues involved
      in educating teams to provide patient-centered cancer care. In the process, we
      question the applicability of a tightly coordinated 'team' concept, and suggest
      the concept of a 'care community' as a more achievable ideal for the way that
      cancer care is commonly delivered. We discuss the implications that this has for
      cancer communication education, and propose three principles to guide the
      development of educational interventions aimed at increasing patient-centeredness
      in cancer care delivery systems.

PMID- 19850439
TI  - Presence of anti-insulin natural autoantibodies in healthy cats and its
      interference with immunoassay for serum insulin concentrations.
AB  - A substance interfering with the enzyme-linked immunosorbent assay (ELISA) for
      feline insulin concentration was investigated in healthy cats. An insulin-binding
      substance isolated from feline serum showed 2 bands at 25 and 50 kDa in SDS-PAGE,
      suggesting the presence of immunoglobulin G (IgG). Insulin-binding IgG from
      healthy cats indeed reduced insulin immunoreactivity in the ELISA for determining
      insulin concentration. The insulin-binding IgG was polyclonal/polyreactive and
      showed certain specificity, high affinity, and high binding capacity, which was
      evaluated by liquid-phase radioimmunoassay with Scatchard plot analysis. Epitope
      analysis revealed that the insulin-binding IgG showed significant binding at
      residues A1-5 and B20-30 of the insulin molecule. Removal of the antibodies from
      serum enabled the determination of serum insulin concentrations by ELISA. Our
      data indicated that serum from healthy cats contained substantial amounts of
      natural autoantibodies combined with insulin, and that the antibodies interfered
      with the heterologous immunoassay for serum insulin concentration.

PMID- 19850441
TI  - [Polyarthritis and nodules on the hands of a 45-year-old man].

PMID- 19850440
TI  - Novel Influenza A (H1N1) outbreak at the U.S. Air Force Academy: epidemiology and
      viral shedding duration.
AB  - BACKGROUND: The U.S. Air Force Academy is an undergraduate institution that
      educates and trains cadets for military service. Following the arrival of 1376
      basic cadet trainees in June 2009, surveillance revealed an increase in cadets
      presenting with respiratory illness. Specimens from ill cadets tested positive
      for novel influenza A (H1N1 [nH1N1])-specific ribonucleic acid (RNA) by real-time
      reverse transcriptase-polymerase chain reaction. PURPOSE: The outbreak
      epidemiology, control measures, and nH1N1 shedding duration are described.
      METHODS: Case patients were identified through retrospective and prospective
      surveillance. Symptoms, signs, and illness duration were documented. Nasal-wash
      specimens were tested for nH1N1-specific RNA. Serial samples from a subset of 53
      patients were assessed for presence of viable virus by viral culture. RESULTS: A
      total of 134 confirmed and 33 suspected cases of nH1N1 infection were identified
      with onset date June 25-July 24, 2009. Median age of case patients was 18 years
      (range, 17-24 years). Fever, cough, and sore throat were the most commonly
      reported symptoms. The incidence rate among basic cadet trainees during the
      outbreak period was 11%. Twenty-nine percent (31/106) of samples from patients
      with temperature <100 degrees F and 19% (11/58) of samples from patients
      reporting no symptoms for > or = 24 hours contained viable nH1N1 virus. Of 29
      samples obtained 7 days from illness onset, seven (24%) contained viable nH1N1
      virus. CONCLUSIONS: In the nH1N1 outbreak under study, the number of cases peaked
      48 hours after a social event and rapidly declined thereafter. Almost one quarter
      of samples obtained 7 days from illness onset contained viable nH1N1 virus. These
      data may be useful for future investigations and in scenario planning.

PMID- 19850442
TI  - The "fever workup" and respiratory culture practice in critically ill trauma
      patients.
AB  - PURPOSE: Fever and leukocytosis (FAL) in critically ill patients often triggers a
      "workup" that includes a respiratory secretion culture (RCx). We evaluated our
      respiratory culture practice associated with FAL. We hypothesized that FAL would
      be associated with a RCx, but would not be associated with a positive culture or
      treating a respiratory infection in critically injured patients during their
      first 14 intensive care unit (ICU) days. MATERIALS AND METHODS: An 18-month
      retrospective analysis was performed on consecutive ICU trauma patients admitted
      for 2 days or more to a level I trauma center. Data collected included
      demographics, injuries, RCxs (bronchoalveolar lavage or tracheal aspirate),
      maximum daily temperature, and a daily leukocyte count during the first 14 ICU
      days. RESULTS: A total of 510 patients with a mean age of 49 and injury severity
      score of 19 were evaluated for a total of 3839 patient-days. Two hundred eleven
      patients had 489 RCxs obtained (2.4 RCxs/patient); 94 (19%) were obtained on
      consecutive days. Obtaining a RCx was associated with fever (relative risk, 4.8;
      95% confidence interval, 4.1-5.8) and the combination of FAL (relative risk, 2.6;
      95% confidence interval, 2.2-3.1), but not leukocytosis alone. Fever,
      leukocytosis, or FAL did not predict a positive RCx. One hundred twenty-eight
      patients were treated for a respiratory infection. Treatment of respiratory
      infections was contrary to the RCx results 24% of the time. The sensitivity and
      specificity of a positive RCx being associated with respiratory infection were
      97% and 46%, respectively. CONCLUSIONS: Fever and leukocytosis were associated
      with the decision to obtain RCxs but were not associated with positive RCxs in
      our ICU practice. Respiratory secretion culture results had a low specificity and
      did not consistently impact treatment decisions. Factors other than fever and
      leukocytosis alone should influence the decision to obtain RCxs during the first
      14 days in the ICU after trauma.

PMID- 19850443
TI  - Extubation versus tracheostomy in withdrawal of treatment-ethical, clinical, and
      legal perspectives.
AB  - The provision of life-sustaining ventilation, such as tracheostomy to critically
      ill patients, is commonly performed. However, the utilization of tracheostomy or
      extubation after a withdrawal of treatment decision is debated. There is a dearth
      of practical information available to aid clinical decision making because
      withdrawal of treatment is a challenging scenario for all concerned. This is
      further complicated by medicolegal and ethical considerations. Care of the
      "hopelessly ill" patient should be based on daily evaluation and comfort making
      it impossible to fit into general algorithms. Although respect for autonomy is
      important in healthcare, it is limited for patients in an unconscious state.
      Beneficence remains the basis for withdrawing treatment in futile cases and
      underpins the "doctrine of double effect." This article presents a relevant
      clinical case of hypoxic brain injury where a question of withdrawal of treatment
      arose and examines the ethical, clinical, and medicolegal considerations inherent
      in such cases, including beneficence, nonmaleficence, and the "sanctity of life
      doctrine." In addition, the considerations of prognosis for recovery, patient
      autonomy, patient quality of life, and patient family involvement, which are
      central to decision making, are addressed. The varying legal frameworks that
      exist internationally regarding treatment withdrawal are also described. Good
      ethics needs sound facts, and despite the lack of legal foundation in several
      countries, withdrawal of treatment remains practiced, and the principles
      described within this article aim to aid clinician decision making during such
      complex and multifaceted end-of-life decisions.

PMID- 19850444
TI  - A new standing posture detector to enable people with multiple disabilities to
      control environmental stimulation by changing their standing posture through a
      commercial Wii Balance Board.
AB  - This study assessed whether two persons with multiple disabilities would be able
      to control environmental stimulation using body swing (changing standing posture)
      and a Wii Balance Board with a newly developed standing posture detection program
      (i.e. a new software program turns a Wii Balance Board into a precise standing
      posture detector). The study was performed according to an ABAB design, in which
      A represented baseline and B represented intervention phases. Both participants
      significantly increased their target response (body swing) to activate the
      control system to produce environmental stimulation during the intervention
      phases. Practical and developmental implications of the findings were discussed.

PMID- 19850445
TI  - Whispering--a single-subject study of glottal configuration and aerodynamics.
AB  - Whisper productions were produced by a single adult male subject over a wide
      range of subglottal pressures, glottal areas, and glottal flows. Dimensional
      measurements were made of these three variables, including glottal perimeter.
      Subglottal pressure was directly obtained by a pressure transducer in a tracheal
      catheter, and wide-band flow with a pneumotach mask. Four types of whispers were
      used-hyperfunctional, hypofunctional, neutral, and postphonation-in addition to
      three levels of loudness (soft, medium, loud). Sequences of the /pae/ syllable
      were used. Video recordings of the larynx were made. The glottis was outlined by
      hand with extrapolation for unseen parts, and area and perimeter were obtained
      through image analysis software. The whisper tokens resulted in the following
      wide ranges: subglottal pressure: 1.3-17 cm H2O; glottal flow: 0.9-1.71 L/s;
      glottal area: 0.065-1.76 m2; and glottal perimeter: 1.09-6.55 cm. Hyperfunctional
      whisper tended to have higher subglottal pressures and lower areas and flows than
      hypofunctional whisper, with neutral and postphonation whisper values in between.
      An important finding is that glottal flow changed more for small changes of area
      when the area was already small, and did not create much flow change when area
      was changed for already larger areas; that is, whisper is "more sensitive" to
      airflow changes for smaller glottal areas. A general equation for whisper
      aerodynamics was obtained, namely, P (subglottal pressure [cm H2O])=C X F
      (glottal flow [cm(3)/s]), where C = 0.052 x A(4) - 0.1913 x A(3) + 0.2577 x A(2) 
      0.1523 x A+0.0388, where A is the glottal area (cm(2)). Another general equation
      for nondimensional terms (pressure coefficient vs Reynolds number) also is
      offered. Implications for whisper flow resistance and aerodynamic power are
      given. These results give insight into whisper aerodynamics and offer equations
      relevant to speech synthesis.

PMID- 19850446
TI  - Change in vibrato rate and extent during tertiary training in classical singing
      students.
AB  - OBJECTIVES: Vibrato is an integral and desirable feature of the classical singing
      voice. For elite singing students, achieving and developing vibrato may
      constitute one of the essential elements of their vocal training, although it is
      not necessarily a focus of that training. STUDY DESIGN: In this longitudinal
      study, we measured vibrato rate (VR) and vibrato extent (VE) and regularity (SD)
      of VR and VE in student singers over the course of four semesters of tertiary
      level voice training at a conservatorium of music to determine how these
      parameters changed during training. METHOD: Fifteen singers completed four
      semesters (2 years) of training. Singers performed four sustained pitches across
      their vocal range. Peaks and troughs of vibrato were isolated from the
      fundamental frequency trace to calculate VR in hertz and VE in semitones.
      RESULTS: Analysis using linear mixed models revealed significant increases in VE
      and decreases in VRSD over time. VR was within expected limits for classical
      singers in all semesters, and small VR reductions were not statistically
      significant between semesters over 2 years of training. VE showed significant
      increases between the start of year 1 and year 2. Periodicity of singers' VR (SD)
      improved over training, with significant decreases to VRSD over time. There was
      no significant change to VESD. CONCLUSIONS: Future studies will ascertain whether
      further changes to VR and VE occur over longer training periods, or whether the
      major changes occur early in tertiary training.

PMID- 19850447
TI  - The butterfly procedure: a new technique and review of the literature for
      treating anterior laryngeal webs.
AB  - Congenital laryngeal webs, subglottic stenosis, and laryngeal atresia result from
      various degrees of failure of airway recanalization as a spectrum. The symptoms
      also range from asymptomatic to dysphonia and severe airway obstruction. There
      are a number of methods for management of symptomatic patients. In this article,
      we discuss a new procedure that was used in the management of two anterior
      laryngeal web patients with relatively acceptable results.

PMID- 19850448
TI  - Short-term impact of the switch from immediate-release to extended-release
      oxcarbazepine in epilepsy patients on high dosages.
AB  - Extended-release oxcarbazepine (OXC) was introduced in Germany in January of
      2008. In principle, this formulation should allow a better tolerability due to
      the less marked serum peak concentration of OXC prior to metabolization to its
      monohydroxy derivate (MHD) that is the active compound. Twenty-seven in-patients
      who had been referred to our epilepsy centre because of their difficult-to-treat
      localization-related epilepsies and had been on immediate-release OXC were
      abruptly switched to extended-release OXC at identical dosages. The adverse event
      profile (AEP) and the QOLIE-10 questionnaire were obtained immediately prior to
      and 5 days after this switch. On both days MHD fasting serum concentrations were
      also measured. After the switch a significant improvement of tolerability and
      quality of life was reported according to AEP and QOLIE-10 (p<0.001).
      Ameliorations were apparent in almost every patient (AEP: 26 of 27 patients,
      QOLIE-10: 23 of 27 patients). The improvement not explained by a drop of MHD
      levels. On the contrary and in line with preclinical data, serum levels of MHD
      rose significantly (p<0.001). We suggest that patients on extended-release OXC
      experience a lower serum concentration peak of the pro-drug OXC.

PMID- 19850450
TI  - Low-frequency EEG oscillations associated with information processing in
      schizophrenia.
AB  - Numerous studies have described attenuated event-related potential (ERP)
      component amplitudes in schizophrenia (e.g., P300, Mismatch Negativity (MMN),
      Error Negativity/Error-Related Negativity (Ne/ERN)). Functional magnetic
      resonance imaging (fMRI) studies have typically shown decreased recruitment of
      diverse brain areas during performance of tasks that elicit the above ERP
      components. Recent research suggests that phase-resetting of slow-oscillations
      (e.g., in the delta and theta bands) underlies the potentials observed in ERP
      averages. Several studies have reported that slow-oscillations are increased in
      amplitude in people with schizophrenia at rest. Few studies have examined event
      related low-frequency oscillations in schizophrenia. We examined event-related
      evoked and induced delta and theta activity in 17 people with schizophrenia and
      17 healthy controls in two go/no-go task variants. We analyzed stimulus-related
      and response-related oscillations associated with correct-hits, correct-rejects
      and false-alarms. Our results reveal a pattern of reduced delta and theta
      activity for task-relevant events in schizophrenia. The findings indicate that
      while low-frequency oscillations are increased in amplitude at rest, they are not
      coordinated effectively in schizophrenia during various information processing
      tasks including target-detection, response-inhibition and error-detection. This
      slow-oscillation coordination abnormality may help explain the decreased
      recruitment of brain areas seen in fMRI studies.

PMID- 19850451
TI  - Using virtual reality to evaluate executive functioning among persons with
      schizophrenia: a validity study.
AB  - Persons with Schizophrenia experience difficulties with Executive Functioning
      (EF) that affect independence and participation in activities. Specifically, EF
      impacts performance in Instrumental Activities of Daily Living (IADL) that
      require flexible thinking and accommodation to complex environments. However,
      less is known how schizophrenia affects EF and individuals' performance in
      activities. IADL performance can be tested using a virtual reality (VR)
      environment that simulates real life activities. The purpose of this study was:
      1) to examine the feasibility and validity of the Virtual Action Planning
      Supermarket (VAP-S) to assess EF in persons with schizophrenia as compared to a
      standardized EF measure (the Behavioral Assessment of Dysexecutive Syndrome,
      BADS); 2) to compare performance of persons with schizophrenia and healthy
      controls in the VAP-S; 3) to assess the ability of the VAP-S to differentiate
      between different levels of EF within schizophrenia; 4) to explore the
      relationships between negative and positive symptoms and performance on the
      tests. Thirty persons with schizophrenia were matched with 30 healthy controls.
      Significant differences in performance between research and control groups were
      detected on the VAP-S and BADS, with the research group performing worse. Large
      variations in number of purchases within the VAP-S by the research group point to
      level of task completion thus secondary analysis was conducted. There was a
      significant negative correlation between level of the negative signs and overall
      performance on the BADS and on most measures of the VAP-S. Results of this study
      support the use the VAP-S to assess EF among persons with Schizophrenia.

PMID- 19850453
TI  - Incidence and correlates of radiation dermatitis in children and adolescents
      receiving radiation therapy for the treatment of paediatric sarcomas.
AB  - AIMS: To investigate the relationship between the maximum grade of skin toxicity,
      radiation dose and clinical variables in children receiving treatment for
      sarcomas involving the bone and soft tissue. MATERIALS AND METHODS: Between
      January 2003 and July 2006, 82 patients with musculoskeletal tumours on an
      Institutional Review Board (IRB)-approved prospective study at St. Jude
      Children's Research Hospital received three-dimensional conformal or intensity
      modulated radiation therapy for local tumour control. Radiation dermatitis was
      graded according to the National Cancer Institute's Common Toxicity Criteria
      version 2.0 during and after radiation therapy. The dose to the skin was
      calculated for each patient from the radiation treatment plan. RESULTS: The
      radiation doses delivered to the primary tumour ranged from 4140 to 7020cGy, with
      a mean dose of 5040cGy. The maximum recorded grade of skin toxicity was: grade 0:
      seven patients (8.6%); grade 1: 26 patients (31.7%); grade 2: 37 patients
      (45.1%); grade 3: 10 patients (12.2%); grade 4: two patients (2.4%). A
      significant association for increased grade of skin toxicity was observed between
      dose (P<0.01), volume of skin treated above 4000cGy (P=0.03), use of a bolus
      (P<0.01), Caucasian race (P<0.01) and related pain (P<0.01). CONCLUSIONS: These
      findings suggest that the delivered dose, use of a bolus, the volume treated, and
      race may be used in the clinical setting to predict patients at risk for skin
      toxicity. Alterations in treatment technique and early therapeutic intervention
      may help to reduce or eliminate radiation-induced skin side-effects and
      associated pain.

PMID- 19850452
TI  - Influence of surface free energy on the adhesion of marine benthic diatom
      Nitzschia closterium MMDL533.
AB  - The self-assembled monolayers (SAMs) with gradient surface free energies were
      prepared by surface grafting of a binary mixture of methyl and vinyl terminated
      trimethoxysilanes on hydrophilic glass slides followed by in situ oxidation of
      vinyl groups into carboxyl groups. Characterized by contact angles, the SAMs
      combined with freshly cleaned glass slides bearing hydroxyl groups were used to
      study the adhesion behavior of marine benthic diatom Nitzschia closterium
      MMDL533. The attachment densities were much higher on hydrophobic CH3-SAMs and
      lower on mixed SAMs with surface free energy of 40.1-50.4 mJ/m2. More gregarious
      adhesion had been found on hydrophobic CH3-SAMs. The percentage removal was in a
      narrow range of 63-80% on the engineered surfaces and was much lower with a value
      of 54% on the hydrophilic slides. Our studies have revealed some subtle but
      interesting differences in attachment and adhesion from the features reported for
      these benthic species, indicating the possible links to different diatom species.

PMID- 19850454
TI  - A population-based study of spinal metastatic disease in South-East Norway.
AB  - AIMS: Spinal metastatic disease (SMD) is a serious complication of cancer. To our
      knowledge, only one population-based study of metastatic spinal cord compression
      (MSCC) has been carried out. The purpose of the present study was to describe
      population-based incidences of SMD that required local treatment, such as
      radiotherapy, surgery or vertebroplasty, including patients with or without cord
      compression, and to characterise the neurological status of these patients.
      MATERIALS AND METHODS: During 18 months, all patients with SMD who received local
      treatment in the South-Eastern Health Region of Norway (population 2.6 million
      inhabitants) were identified and their medical records were reviewed. RESULTS: In
      total, 1002 patients were included; 83% had multiple lesions in the spine; 39%
      had SMD at the time of the primary cancer diagnosis. At the start of local
      treatment, 31% had MSCC and 11% were not able to walk. The prevalence of MSCC at
      the time of cancer diagnosis was 0.36%. The annual incidences per 100,000
      inhabitants were 26.0 for SMD and 8.1 for MSCC. CONCLUSION: Population-based
      incidences of SMD requiring local treatment have been reported for the first
      time. The prevalence of MSCC at the time of cancer diagnosis was higher than
      previously reported. A more precise definition of MSCC and more population-based
      studies are needed to reduce selection bias when comparing different studies.

PMID- 19850455
TI  - Isolation and characterization of aniline degradation slightly halophilic
      bacterium, Erwinia sp. Strain HSA 6.
AB  - The isolated strain HSA6 is classified as Erwinia amylovora based on 16S rDNA
      sequence and the morphological and physiological properties. Strain HSA6 is the
      first reported E. amylovora in pure culture growing with aniline as sole electron
      donor and carbon source. The suitable pH for strain HSA6 is wide (from 5 to 11).
      Strain HSA6 is slightly halophilic with growth occurring at 0-10% (v/v) NaCl, and
      the suitable NaCl concentration for strain HSA6 is from 0% to 6%. The number of
      bacteria appeared to decrease with an increase in aniline concentration. The
      number of bacteria appeared to be constant as the wastewater concentration
      increased from 0% to 20%. However, the number of cells decreased with an increase
      in wastewater concentration from 30% to 50% and grew very slowly at 50%. The
      degradation rate of aniline was 100% at 0.5% aniline concentration after 24 h
      culture. The degradation rate of aniline was found to descend as the
      concentration of aniline increased from 0.5% to 3% and rose as the culture time
      increased. Strain HSA6 contains a plasmid with molecular weight higher than 42
      kDA. Plasmid curing test and quantitative degradation test showed that strain
      requires the plasmid for aniline degradation. The gene cluster degrading aniline
      was determined in the plasmid by PCR amplification.

PMID- 19850456
TI  - Determination and distribution of cry-type genes in halophilc Bacillus
      thuringiensis isolates of Arabian Sea sedimentary rocks.
AB  - Bacillus thuringiensis produces insecticidal crystal during its sporulation
      phase. In this study, marine sediments from Arabian Sea along coastal area of
      Pakistan were examined for the occurrence of B. thuringiensis. On the basis of
      morphological and biochemical properties, 31 out of 200 colonies were assigned to
      B. thuringiensis. Isolated strains were characterized on the basis of cry genes
      profile. PCR approach was used to analyze the presence of different crystal toxin
      encoding genes with six pairs of universal primers that could detect the cry1,
      cry4, cry7, cry8, cry9, and cry10 genes. Strains containing cry1 genes were the
      most abundant in our collection (49.5%). Seventeen different profiles of cry
      genes were identified, i.e., twelve harboring two cry genes while five profiles
      of more than two cry genes. The characterization of these strains provided useful
      information on the ecological patterns of distribution of B. thuringiensis and
      opportunities for the selection of new strains to develop novel bio-insecticidal
      products.

PMID- 19850449
TI  - Mitochondria, oxidative stress, and temporal lobe epilepsy.
AB  - Mitochondrial oxidative stress and dysfunction are contributing factors to
      various neurological disorders. Recently, there has been increasing evidence
      supporting the association between mitochondrial oxidative stress and epilepsy.
      Although certain inherited epilepsies are associated with mitochondrial
      dysfunction, little is known about its role in acquired epilepsies such as
      temporal lobe epilepsy (TLE). Mitochondrial oxidative stress and dysfunction are
      emerging as key factors that not only result from seizures, but may also
      contribute to epileptogenesis. The occurrence of epilepsy increases with age, and
      mitochondrial oxidative stress is a leading mechanism of aging and age-related
      degenerative disease, suggesting a further involvement of mitochondrial
      dysfunction in seizure generation. Mitochondria have critical cellular functions
      that influence neuronal excitability including production of adenosine
      triphosphate (ATP), fatty acid oxidation, control of apoptosis and necrosis,
      regulation of amino acid cycling, neurotransmitter biosynthesis, and regulation
      of cytosolic Ca(2+) homeostasis. Mitochondria are the primary site of reactive
      oxygen species (ROS) production making them uniquely vulnerable to oxidative
      stress and damage which can further affect cellular macromolecule function, the
      ability of the electron transport chain to produce ATP, antioxidant defenses,
      mitochondrial DNA stability, and synaptic glutamate homeostasis. Oxidative damage
      to one or more of these cellular targets may affect neuronal excitability and
      increase seizure susceptibility. The specific targeting of mitochondrial
      oxidative stress, dysfunction, and bioenergetics with pharmacological and non
      pharmacological treatments may be a novel avenue for attenuating epileptogenesis.

PMID- 19850457
TI  - Glucose metabolism and programmed cell death: an evolutionary and mechanistic
      perspective.
AB  - Over the last decade, cellular glucose metabolism has emerged as a central player
      in the mechanisms of programmed cell death (PCD). We examined the metabolic
      foundations of apoptosis from a Darwinian context and suggest that PCD has
      evolved from the cellular response to metabolic stress, most notably in relation
      to glucose metabolism. Whilst apoptosis and other forms of PCD are essential to
      the development, maintenance and survival of multicellular organisms, it is now
      evident that controlled and selective cell death confers fitness advantages in
      unicellular organisms. All species may thus harbour a fundamental relationship
      between the availability of basic nutrients and life/death decisions. This
      evolutionary perspective may inform our understanding of PCD in its many guises.

PMID- 19850459
TI  - Application of the dynamic model of Saeman to an industrial rotary kiln
      incinerator: numerical and experimental results.
AB  - In order to simulate granular materials structure in a rotary kiln under the
      steady-state regime, a mathematical model has been developed by Saeman (1951).
      This model enables the calculation of the bed profiles, the axial velocity and
      solids flow rate along the kiln. This model can be coupled with a thermochemical
      model, in the case of a reacting moving bed. This dynamic model was used to
      calculate the bed profile for an industrial size kiln and the model projections
      were validated by measurements in a 4 m diameter by 16 m long industrial rotary
      kiln. The effect of rotation speed under solids bed profile and the effect of the
      feed rate under filling degree were established. On the basis of the calculations
      and the experimental results a phenomenological relation for the residence time
      estimation was proposed for the rotary kiln.

PMID- 19850458
TI  - Regulation of cell death by the ubiquitin-proteasome system.
AB  - The regulation of apoptosis (programmed cell death) has been the subject of a
      vast body of research because of its implications in normal development, tissue
      homeostasis and a wide range of diseases. The ubiquitin-proteasome system (UPS)
      plays a prominent role in the control of apoptosis by targeting key cell death
      proteins, including caspases, the central executioners of apoptosis. Here we
      summarize the major findings on the function of the UPS in both pro- and anti
      apoptotic regulation.

PMID- 19850460
TI  - Vermicomposting of source-separated human faeces for nutrient recycling.
AB  - The present study examined the suitability of vermicomposting technology for
      processing source-separated human faeces. Since the earthworm species Eisenia
      fetida could not survive in fresh faeces, modification in the physical
      characteristics of faeces was necessary before earthworms could be introduced to
      faeces. A preliminary study with six different combinations of faeces, soil and
      bulking material (vermicompost) in different layers was conducted to find out the
      best condition for biomass growth and reproduction of earthworms. The results
      indicated that SVFV combination (soil, vermicompost, faeces and vermicompost -
      bottom to top layers) was the best for earthworm biomass growth indicating the
      positive role of soil layer in earthworm biomass growth. Further studies with
      SVFV and VFV combinations, however, showed that soil layer did not enhance
      vermicompost production rate. Year-long study conducted with VFV combination to
      assess the quality and quantity of vermicompost produced showed an average
      vermicompost production rate of 0.30kg-cast/kg-worm/day. The vermicompost
      produced was mature as indicated by low dissolved organic carbon (2.4+/-0.43mg/g)
      and low oxygen uptake rate (0.15+/-0.09mg O(2)/g VS/h). Complete inactivation of
      total coliforms was noted during the study, which is one of the important
      objectives of human faeces processing. Results of the study thus indicated the
      potential of vermicomposting for processing of source-separated human faeces.

PMID- 19850461
TI  - Metallurgical use of glass fractions from waste electric and electronic equipment
      (WEEE).
AB  - Within the European Union, it is estimated that between 8 and 9 million tons of
      waste electric and electronic equipment (WEEE) arises annually, of which
      television sets and computers account for an important part. Traditionally,
      Cathode Ray Tubes (CRT) have been used for TVs and computer monitors, but are
      rapidly being replaced by flat-screen technology. Only part of the discarded CRT
      glass is being recycled. Primary smelters use large amounts of silica flux to
      form iron-silicate slag, and can, in most cases, tolerate lead input. Use of
      discarded CRT glass in copper smelting is a potential alternative for utilization
      of the glass. The mineralogical composition of a slag sampled during ordinary
      slag praxis has been compared with that of a mixture of slag and CRT glass when
      re-melted and slowly cooled. Slag (iron-silicate slag) from Boliden Mineral AB,
      Sweden, was used for the experiments. Slag and glass have been mixed in various
      proportions: pure slag, pure glass, 90% slag-10% glass and 65% slag-35% glass,
      and heated in an inert atmosphere up to 1400 degrees C in a Netzsch Thermal
      Analysis (TA) instrument. The re-melted material has been analyzed using X-ray
      diffraction (XRD) and scanning electron microscopy (SEM) to determine changes in
      mineralogical composition after mixing with glass. The results show that the main
      mineralogical component of the slag is fayalite; the CRT glass is amorphous. The
      main crystalline phases of the slag do not change with addition of glass. An
      amorphous phase appears when the addition of glass is increased, which gives the
      sample a different structure.

PMID- 19850462
TI  - Element associations in ash from waste combustion in fluidized bed.
AB  - The incineration of MSW in fluidized beds is a commonly applied waste management
      practice. The composition of the ashes produced in a fluidized bed boiler has
      important environmental implications as potentially toxic trace elements may be
      associated with ash particles and it is therefore essential to determine the
      mechanisms controlling the association of trace elements to ash particles,
      including the role of major element composition. The research presented here uses
      micro-analytical techniques to study the distribution of major and trace elements
      and determine the importance of affinity-based binding mechanisms in separate
      cyclone ash particles from MSW combustion. Particle size and the occurrence of Ca
      and Fe were found to be important factors for the binding of trace elements to
      ash particles, but the binding largely depends on random associations based on
      the presence of a particle when trace elements condensate in the flue gas.

PMID- 19850463
TI  - Label-free electrochemical DNA biosensor array for simultaneous detection of the
      HIV-1 and HIV-2 oligonucleotides incorporating different hairpin-DNA probes and
      redox indicator.
AB  - A label-free electrochemical DNA biosensor array was developed as a model system
      for simultaneous detection of multiplexed DNAs using microlitres of sample. A
      novel multi-electrode array was comprised of six gold working electrodes and a
      gold auxiliary electrode, which were fabricated by gold sputtering technology,
      and a printed Ag/AgCl reference electrode was fabricated by screen-printing
      technology. The DNA biosensor array for simultaneous detection of the human
      immunodeficiency virus (HIV) oligonucleotide sequences, HIV-1 and HIV-2, was
      fabricated in sequence by self-assembling each of two kinds of thiolated hairpin
      DNA probes onto the surfaces of the corresponding three working electrodes,
      respectively. The hybridization events were monitored by square wave voltammetry
      using methylene blue (MB) as a hybridization redox indicator. The oxidation
      currents of MB accumulated on the array decreased with increasing the
      concentration of HIVs due to higher affinity of MB for single strand rather than
      double strands of DNA. Under the optimized conditions, the peak currents were
      linear over ranges from 20 to 100 nM for HIV-1 and HIV-2, with the same detection
      limits of 0.1 nM (S/N=3), respectively. The biosensor array showed a good
      specificity without the obvious cross-interference. Furthermore, single-base
      mutation oligonucleotides and random oligonucleotides can be easily discriminated
      from complementary target DNAs. This work demonstrates that different hairpin-DNA
      probes can be used to design the label-free electrochemical biosensor array for
      simultaneous detection of multiplexed DNA sequences for various clinical
      applications.

PMID- 19850464
TI  - On-chip electrical impedance tomography for imaging biological cells.
AB  - Electrical impedance tomography is an imaging technology that spatially
      characterizes the electrical properties of an object. We present a miniaturized
      electrical impedance tomography system that can image the electrical conductivity
      distribution within a two-dimensional cell culture. A chip containing a circular
      16-electrode array was fabricated using printed circuit board developing
      technology and used to inject current and to measure spatial voltage across the
      object. The signal stimulation and voltage data acquisition were performed using
      an impedance analyzer, operating in four-electrode mode. An open source software,
      EIDORS was used for image reconstruction. Finite element modelling was used to
      simulate the image reconstruction process by imaging two ellipsoidal phantoms in
      the circular 16-electrode array. The effect of the regularization parameter in
      the reconstruction algorithm and the influence from noise on the fidelity of the
      images has been numerically analyzed. Experimentally, we show reconstructed
      images of a multi-nuclear single cellular organism, Physarum Polycephalum,
      demonstrating the first step towards impedance imaging of single cells in
      culture. Our system provides a non-invasive lab-on-a-chip technology for
      spatially mapping the electrical properties of single cells, which would be
      significant and useful for diagnostic and clinical applications.

PMID- 19850465
TI  - FTRIFS biosensor based on double layer porous silicon as a LC detector for target
      molecule screening from complex samples.
AB  - Post-column identification of target compounds in complex samples is one of the
      major tasks in drug screening and discovery. In this work, we demonstrated that
      double layer porous silicon (PSi) attached with affinity ligand could serve as a
      sensing element for post-column detection of target molecule by Fourier
      transformed reflectometric interference spectroscopy (FTRIFS), in which trypsin
      and its inhibitor were used as the model probe-target system. The double layer
      porous silicon was prepared by electrical etching with a current density of 500
      mA/cm(2), followed by 167 mA/cm(2). Optical measurements indicated that trypsin
      could infiltrate into the outer porous layer (porosity 83.6%), but was excluded
      by the bottom layer (porosity 52%). The outer layer, attached with trypsin by
      standard amino-silane and glutaraldehyde chemistry, could specifically bind with
      the trypsin inhibitor, acting as a sample channel, while the bottom layer served
      as a reference signal channel. The binding event between the attached trypsin and
      trypsin inhibitor samples could be detected by FTRIFS in real-time through
      monitoring the optical thickness change of the porous silicon layer. The baseline
      drift caused by sample matrix variation could be effectively eliminated by a
      signal correction method. Optical signals had a linear relationship with the
      concentration of trypsin inhibitor in the range of 10-200 ng mL(-1). The FTRIFS
      biosensor based on double layer porous silicon could be combined with a UV
      detector for screening the target molecule from complex component mixtures
      separated by a LC column. Using an LC-UV-FTRIFS system, a fraction containing a
      trypsin inhibitor could be separated from a soybean extract sample and identified
      in real-time.

PMID- 19850466
TI  - What can metabolomics learn from genomics and proteomics?
AB  - After nearly a decade, metabolomics has begun to acquire some credence in the
      scientific community although its acceptance cannot be compared with that of its
      forerunners, genomics and proteomics. The legitimization of metabolomics as a
      valid scientific entity depends on the size of the research community it
      influences. By far the most effective medium for inoculation is the web
      infrastructure: public servers that accommodate experimental data, simple formats
      and guidelines for their interpretation, and connectivity between data and tools
      for analysis. When these elements satisfy the condition to initiate a social
      epidemic, metabolomics will be accepted as a fundamental data-driven science that
      can unite hitherto independently conducted research disciplines.

PMID- 19850467
TI  - Functional metagenomics for enzyme discovery: challenges to efficient screening.
AB  - Metagenomics has emerged as an alternative approach to conventional microbial
      screening that allows exhaustive screening of microbial genomes in their natural
      environments. Despite the potential usefulness of this approach, functional
      analysis of the metagenome is often problematic because of insufficient and
      biased expression of the cloned genes in Escherichia coli. This review highlights
      recent studies on the screening of metagenomic libraries and discusses some
      possible solutions for overcoming the expression problem in function-based
      screening.

PMID- 19850468
TI  - The influence of chemotherapy on bone mineral density, quantitative
      ultrasonometry and bone turnover in pre-menopausal women with breast cancer.
AB  - INTRODUCTION: The effects of doxorubicin/cyclophosphamide (A/C; 6 cycles)
      chemotherapy on bone mineral density (BMD), quantitative ultrasonography (QUS)
      and bone turnover markers in pre-menopausal women with oestrogen receptor
      negative breast cancer (BC) were compared with age-matched controls. METHODS:
      Among 106 women (BC=53, controls=53), BMD (spine and hip), QUS (calcaneus and
      phalanges) and bone marker levels were measured at baseline, 6 and 12 months.
      Correlations between parameters were determined by Spearman's rho. RESULTS: All
      BC patients became amenorrhoeic after chemotherapy and remained so for the
      duration of treatment. BC patients had significant bone loss at all sites (P.005)
      and significant increases in bone turnover (P.05). There were significant
      correlations between BMD, QUS and bone markers (P.05). CONCLUSIONS: Results
      confirm A/C's deleterious influence on bone health in pre-menopausal women with
      BC and established QUS's utility for monitoring bone effects. Large-scale
      longitudinal studies are needed to further understand and prevent bone changes
      following chemotherapy.

PMID- 19850469
TI  - Macronutrients, fatty acids, cholesterol and pancreatic cancer.
AB  - A role of diet and nutrition in pancreatic carcinogenesis has been suggested, but
      the association between selected macronutrients, fatty acids, cholesterol and
      pancreatic cancer remains controversial. We analysed data from a hospital-based
      case-control study conducted in Italy between 1991 and 2008, including 326 cases
      (174 men and 152 women) with incident pancreatic cancer, and 652 controls (348
      men and 304 women) frequency-matched to cases by sex, age and study centre. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple
      logistic regression models conditioned on age, sex and study centre, and adjusted
      for year of interview, education, tobacco smoking, history of diabetes and energy
      intake. A positive association was found for animal proteins (OR=1.85 for the
      highest versus the lowest quintile of intake; 95% CI: 1.15-2.96; p for
      trend=0.039), whereas a negative association was observed for sugars (OR=0.52;
      95% CI: 0.31-0.86; p for trend=0.003). Non-significant negative associations
      emerged for vegetable proteins (OR=0.69) and polyunsaturated fatty acids
      (OR=0.67). In conclusion, a diet poor in animal proteins and rich in sugars
      (mainly derived from fruit) appears to have a beneficial effect on pancreatic
      cancer risk.

PMID- 19850470
TI  - Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin
      treatment in childhood: relevance of age and dose as risk factors.
AB  - PURPOSE: The long-term outcome of platinum-induced nephrotoxicity is unknown.
      This prospective single-centre longitudinal cohort study evaluated long-term
      changes following treatment in childhood. METHODS: 63 children treated with
      platinum (27 cisplatin, 24 carboplatin and 12 both) were studied at the end of
      treatment (End), 1 year and 10 years later. No child received ifosfamide.
      Glomerular filtration rate (GFR), serum calcium and magnesium (Mg) were measured,
      and total nephrotoxicity score (N(s)) was graded. RESULTS: There was no
      significant overall change in renal function over time in any treatment group
      (cisplatin, carboplatin or combined). Apart from marginally reduced median GFR
      (84 ml/min/1.73 m(2)) and Mg (0.68 mmol/l) at End of cisplatin, median GFR, Ca
      and Mg were normal at all times in each group. At 10 years, GFR was <60
      ml/min/1.7 3m(2) in 11%, N(s) grade was severe in 15% and oral Mg supplements
      were required in 7% cisplatin patients. After cisplatin, older age at treatment
      was correlated with lower GFR at 10 years (p=0.005), and higher N(s) at End and
      10 years (both p=0.02). After carboplatin treatment, older age was associated
      with lower GFR at all times, and with higher N(s) at End and 1 year (all p<0.03).
      Higher cisplatin dose rate (>40 mg/m(2)/day) was associated with higher N(s) at 1
      year (p=0.02) and higher carboplatin dose with lower Mg at 1 year and with higher
      N(s) at 1 and 10 years (all p<0.008). CONCLUSIONS: Platinum nephrotoxicity did
      not change significantly over 10 years. Its severity was correlated to older age
      at treatment, and at some time points to higher cisplatin dose rate and higher
      cumulative carboplatin dose.

PMID- 19850471
TI  - Application of the severity parameter for predicting viscosity during
      hydrothermal processing of dewatered sewage sludge for a commercial PFBC plant.
AB  - Dewatered sewage sludge (approximately 80% water, but with low fluidity) was
      liquidized by hydrothermal treatment in order to make coal-water paste (CWP) for
      use in a pressurized-fluidized-bed-combustion (PFBC) power plant. Prediction of
      the viscosity of the dewatered sewage sludge during batch reactor hydrothermal
      liquefaction is important in order to avoid inputting excess energy. A single
      parameter, the severity parameter, has been used to predict viscosity during the
      hydrothermal process. The relationship between the viscosity of the slurry made
      from dewatered sewage sludge and the severity value was investigated. Viscosity
      reduction was associated with an increase in the severity value and was dependent
      on reaction temperature and time. It was concluded that predicting the viscosity
      of dewatered sewage sludge during the hydrothermal process by means of the
      severity parameter is possible. This method is expected to provide a useful
      guideline for choosing reaction conditions based on prediction of the viscosity
      of the sludge slurry during the hydrothermal process.

PMID- 19850472
TI  - Immobilization of intracellular carbonyl reductase from Geotrichum candidum for
      the stereoselective reduction of 1-naphthyl ketone.
AB  - Different cell disintegration methods were used for the liberation of
      intracellular carbonyl reductase from Geotrichum candidum, in its active form.
      Solid shear (bead milling) was proved to be the best method for the extraction of
      the enzyme. Various solid supports were checked for the immobilization of the
      purified enzyme. Carbonyl reductase was immobilized on silica with an optimized
      protein loading of 4 mg/g support. Cross-linking with glutaraldehyde rendered the
      preparation more stable and suitable for use in consecutive batches. Carbonyl
      reductase of G. candidum immobilized on silica support and cross-linked by
      glutaraldehyde was found to be highly efficient biocatalyst formulation for the
      production of S(-)-1-(1'-naphthyl) ethanol.

PMID- 19850473
TI  - Pentacycle derivatives as cannabinoid CB1 receptor ligands.
AB  - Cannabinoid CB-1 receptors have been the focus of extensive studies since the
      first clinical results of rimonabant (SR141716) for the treatment of obesity and
      obesity-related metabolic disorders were reported in 2001. To further evaluate
      the properties of CB receptors, we have designed and efficiently prepared a
      series of pentacycle derivatives. Five of the new compounds which displayed high
      in vitro rCB1 binding affinities were assayed for binding to hCB2 receptor.
      Noticeably, 2-(5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-(5-methyl-1,3,4
      thiadiazol-2-yl)-1H-pyrazol-3-yl)-5-(1-(trifluoromethyl)cyclopropyl)-1,3,4
      oxadiazole (16l) demonstrated good binding affinity and decent selectivity for
      rCB1 receptor (IC(50)=1.72 nM, hCB2/rCB1=142).

PMID- 19850474
TI  - Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase
      (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors.
AB  - The screening of known medicinal agents against new biological targets has been
      shown to be a valuable approach for revealing new pharmacology of marketed
      compounds. Recently, carbamate, urea and ketone inhibitors of fatty acid amide
      hydrolase (FAAH) have been described as promising treatments for pain, anxiety,
      depression and other CNS-related conditions. In order to find novel FAAH
      inhibitors, a focused screen of molecules containing potentially reactive
      moieties or having in vivo effects that are possibly relevant to the biology of
      FAAH was conducted. These studies revealed phenmedipham 13 and amperozide 14 to
      be inhibitors of human FAAH, with an IC(50) of 377 nM and 1.34 microM,
      respectively.

PMID- 19850475
TI  - Synthesis and in vitro and in vivo evaluation of manganese(III) porphyrin-dextran
      as a novel MRI contrast agent.
AB  - 5-(4-Aminophenyl)-10,15,20-tris(4-sulfonatophenyl) manganese(III) porphyrin
      conjugated with dextran was synthesized. Its potential of being used as a tumor
      targeting magnetic resonance imaging contrast agent was evaluated in vitro and in
      vivo. The results demonstrated that the compound has a longitudinal relaxivity
      (R(1)) higher than Gd-DTPA, low cytotoxicity and binding specificity to tumor
      cell membrane.

PMID- 19850476
TI  - Preliminary SAR analysis of novel antiproliferative N(6),5'-bis-ureidoadenosine
      derivatives.
AB  - A preliminary library of novel N(6),5'-bis-ureidoadenosine analogs and related
      derivatives was prepared and tested for activity against the NCI 60 panel of
      human cancers. A 2'-O-TBS group was found to be necessary, but not sufficient,
      for optimal antiproliferative activity. Neither the N(6)- nor 5'-ureido
      substituents were sufficient to achieve significant antiproliferative effects
      when present in the absence of the other. The 2'-O-TBS, and N(6),5'-bis-ureido
      substitution patterns were found to be necessary for optimal antiproliferative
      activity.

PMID- 19850477
TI  - Are males with early breast cancer treated differently from females with early
      breast cancer in Australia and New Zealand?
AB  - Breast cancer in males is much rare than in females so in practice, male breast
      cancer treatment is likely to follow the guidelines developed for female breast
      cancer patients. The objective of this study is to compare the characteristics
      and treatment pattern of male breast cancer patients with comparable subgroups of
      female breast cancer patients using data submitted to the National Breast Cancer
      Audit. This is a retrospective analysis of 151 male breast cancers diagnosed and
      treated between 2000 and 2008. Most of the male early breast cancer cases in this
      group were symptomatic ones in men aged >50 years with one invasive tumour. There
      was a similar proportion of lymph node positive cancer among males and females,
      although male breast cancer was more likely to be unifocal (P=0.007) and
      oestrogen receptor positive (P=0.001). Male breast cancer patients almost always
      underwent mastectomy and a significant proportion of them (11%) received no
      surgical treatment. There were no differences in axillary surgery although males
      were more likely to undergo a level 2 axillary surgery and less likely to have
      sentinel node biopsy. Male patients were significantly less likely to undergo
      radiotherapy, chemotherapy or hormonal therapy for oestrogen receptor positive
      tumours. CONCLUSION: While the female oriented treatment guidelines are
      available, male patients with early breast cancer received different surgical and
      adjuvant treatment from comparable females.

PMID- 19850478
TI  - Debating the mathematical model to validate the sentinel lymph biopsy techniques
      in breast cancer patients. The danger of bias and its practical implications.
AB  - BACKGROUND: Sentinel node biopsy (SNB) is an effective alternative to axillary
      lymph node dissection (ALD) for axillary staging. SNB (test) needs a validation
      period in which ALD (the gold standard) is always performed. Sensitivity,
      specificity and predictive values (PV) are used to define the accuracy of the
      procedure. We hypothesise that, during the period of validation, a bias is
      produced if the result of SNB is included as a part of the ALD. PATIENTS AND
      METHODS: A hypothetical population of 350 patients was analysed. First analyses
      were performed by including the sentinel lymph node as a part of 'the rest of the
      axilla'. Second analyses were re-done according to our theory, and sentinel lymph
      node was considered outside 'the rest of the axilla'. Sensitivity, specificity
      and PV were compared for both models. RESULTS: First group (classic) -
      sensitivity: 94%; specificity: 100%; positive PV: 100%; negative PV: 97%. Second
      group (new proposed model) - sensitivity: 87%; specificity: 81%; positive PV:
      44%; negative PV: 97%. CONCLUSION: The classic concept of sentinel lymph node to
      calculate sensitivity, specificity and positive PV can result in a bias. The
      magnitude of this bias will vary in terms of the obtained values, but its
      direction is always optimistic.

PMID- 19850479
TI  - Safety and efficacy of contra-lateral breast reduction for women with mammary
      hypertrophy undergoing mastectomy for breast cancer.
AB  - Women with mammary hypertrophy undergoing mastectomy for breast cancer suffer
      disability because of disproportionate asymmetry. The case notes of all women
      with mammary hypertrophy undergoing mastectomy and immediate contra-lateral
      reduction mammaplasty for primary breast cancer from February 2001 to December
      2008 were reviewed. Thirty-three women were identified of whom twenty-seven
      underwent inferior pedicle reduction mammaplasty and six inferior dermoglandular
      pedicle reduction with free nipple graft. The duration of surgery ranged from 75
      to 146 (median 110) minutes. Between 475 and 2350 (median 1090) grams of breast
      tissue was excised from the contra-lateral breast. No immediate or delayed
      complications were observed and there were no delays in commencing adjuvant
      therapy. Immediate contra-lateral breast reduction in women with mammary
      hypertrophy undergoing mastectomy for breast cancer is safe and effective means
      of reducing the physical, psychological and cosmetic problems associated with
      unilateral mammary hypertrophy following mastectomy.

PMID- 19850480
TI  - Oxidation of potassium channels by ROS: a general mechanism of aging and
      neurodegeneration?
AB  - A wealth of evidence underscores the tight link between oxidative stress,
      neurodegeneration and aging. When the level of excess reactive oxygen species
      (ROS) increases in the cell, a phenomenon characteristic of aging, DNA is
      damaged, proteins are oxidized, lipids are degraded and more ROS are produced,
      all culminating in significant cell injury. Recently we showed that in the
      nematode, Caenorhabditis elegans, oxidation of K(+) channels by ROS is a major
      mechanism underlying the loss of neuronal function. The C. elegans results
      support an argument that K(+) channels controlling neuronal excitability and
      survival might provide a common, functionally important substrate for ROS in
      aging mammals. Here we discuss the implications that oxidation of K(+) channels
      by ROS might have for the mammalian brain during normal aging, as well as in
      neurodegenerative diseases such as Alzheimer's and Parkinson's. We argue that
      oxidation of K(+) channels by ROS is a common theme in the aging brain and
      suggest directions for future experimentation.

PMID- 19850481
TI  - Is nurse-managed blood glucose control in critical care as safe and effective as
      the traditional sliding scale method?
AB  - BACKGROUND: Hyperglycaemia occurs in a substantial proportion of critically ill
      patients. Recent studies have demonstrated that controlling blood glucose in
      critically ill patients can improve outcomes (Boord et al., 2001). Traditionally,
      blood glucose is controlled by the sliding scale method. A pre-defined dose of
      intravenous insulin is infused for each glucose level. Revisions to the
      prescription are frequently necessary when it is ineffective. The objective of
      this review is to assess the effectiveness, safety and feasibility of nurse
      managed protocols that require minimal physician input. METHODS: An electronic
      search was performed on the Medline, CINAHL and EMBASE databases from 1996 to
      2008. The objective of this work was to assess nurse-managed glycaemic control in
      critically ill patients. The target blood glucose was required to be less than
      8.3mmol/L. RESULTS: Fourteen papers met the inclusion criteria. Eight studies
      compared their protocol to the previous method of glucose control (Table 1). In
      all cases there was an improvement. Time to reach target was less and time spent
      within target range was greater. All but one study reduced episodes of
      hypoglycaemia with the new protocol. Six studies developed their protocol as a
      quality improvement project and did not use a control group (Table 2).
      CONCLUSION: An insulin infusion protocol (IIP) that uses the last two blood
      glucose levels in order to determine the new infusion rate is better at
      maintaining glycaemic control than the traditional sliding scale method. A
      protocol that allows a nurse to commence and maintain the infusion is as safe and
      more effective than the traditional sliding scale method.

PMID- 19850482
TI  - Matrix-assisted autologous chondrocyte implantation into a 14cm(2) cartilage
      defect, caused by steroid-induced osteonecrosis.
AB  - Modern chemotherapy protocols have improved the prognosis for acute lymphoblastic
      leukaemia (ALL), one of the most common paediatric malignancies, but their high
      dose corticosteroids lead to osteonecrosis in up to 9% of ALL patients. A 13.5
      year-old female patient developed massive osteonecrosis of the right knee after
      successful ALL treatment. She presented at the age of 17.5 years as a candidate
      for knee arthroplasty after conservative treatment had failed. Magnetic Resonance
      Imaging (MRI) revealed severe osteonecrosis, with the cartilage layer of the
      medial femoral condyle completely detached from the bone. We preferred to attempt
      a two-step biological reconstruction in this young patient, with arthroscopy of
      the right knee joint and removal of the dissected cartilage layer of the medial
      condyle. Matrix-assisted autologous chondrocyte implantation (MACI) was performed
      with harvested chondrocytes after imaging had indicated vital bone remodelling.
      Rehabilitation was according to MACI guidelines and after 5.5 years, the patient
      shows continuous clinical improvement and is satisfied with the result. The
      Lysholm score improved from 45 to 99 and Tegner's activity score from 1 to 4. MRI
      follow-up showed a solid cartilage layer covering the medial condyle as a result
      of bone and chondral regeneration. Even if this approach had failed, bone
      remodelling would have still provided better conditions for knee arthroplasty.

PMID- 19850483
TI  - Peptide inhibitors of HIV-1 integrase: from mechanistic studies to improved lead
      compounds.
AB  - The HIV-1 integrase enzyme (IN) catalyzes integration of viral DNA into the host
      genome. We previously developed peptides that inhibit IN in vitro and HIV-1
      replication in cells. Here we present the design, synthesis and evaluation of
      several derivatives of one of these inhibitory peptides, the 20-mer IN1. The
      peptide corresponding to the N-terminal half of IN1 (IN1 1-10) was easier to
      synthesize and much more soluble than the 20-mer IN1. IN1 1-10 bound IN with
      improved affinity and inhibited IN activity as well as HIV replication and
      integration in infected cells. While IN1 bound the IN tetramer, its shorter
      derivatives bound dimeric IN. Mapping the peptide binding sites in IN provided a
      model that explains this difference. We conclude that IN1 1-10 is an improved
      lead compound for further development of IN inhibitors.

PMID- 19850484
TI  - Biochemical and cytochemical studies of the enzymatic activity of the venom
      glands of workers of honey bee Apis mellifera L. (Hymenoptera, Apidae).
AB  - Biochemical studies revealed that the activity of some hydrolytic enzymes from
      the venom glands of honey bee Apis mellifera was higher in workers of 14 days of
      age than in those of 40 days. Among these enzymes, the highest activity was
      recorded for acid phosphatase, which was cytochemically detected throughout the
      length of the secretory filament and surrounding the canaliculi of the distal
      region of the reservoir. The acid phosphatase was considered to be a typical
      secretion product, since it was present in the cytoplasm as well as in the
      canaliculi of the secretory cells.

PMID- 19850485
TI  - Fricke gel-layer dosimetry in high dose-rate brachytherapy.
AB  - The aim of this study was to evaluate the reliability of Fricke gel-layer
      dosimeters for the measurement of in-phantom dose distributions produced by a
      ((192))Ir brachytherapy source. The doses obtained were compared to measurements
      performed with thermoluminescent dosimeters and treatment planning calculations.
      Fricke gel-layer dosimeters have proven to be a promising tool to measure three
      dimensional dose distributions in high dose-rate brachytherapy.

PMID- 19850486
TI  - Real-time monitoring of arsenic filtration by granular ferric hydroxide.
AB  - Contamination of drinking water by arsenic is a serious public health issue in
      many parts of the world. One recent approach to this problem has been to filter
      out arsenic by use of granular ferric hydroxide (GFH), an adsorbent developed
      specifically for the selective removal of arsenic from water. Previous studies
      have documented the efficiency and high treatment capacity of this approach. We
      present a novel X-ray fluorescence method to monitor the accumulation of arsenic
      within a specially designed GFH column, as both a function of time (or water
      volume) and location along the column. Using a miniature X-ray tube and silicon
      PiN diode detector, X-ray fluorescence is used to detect characteristic X-rays of
      arsenic excited from within the GFH. Trials were performed using a water flow
      rate of approximately 1.5 L per hour, with an added arsenic concentration of
      approximately 1000 microg per litre. In this paper, trial results are presented
      and potential applications described.

PMID- 19850487
TI  - Application of radioactive sources in analytical instruments for planetary
      exploration.
AB  - Radioactive isotopes have been used in analytical instrumentation for planetary
      exploration since the very beginning of the space age. An Alpha Scattering
      Instrument (ASI) on board the Surveyor 5, 6 and 7 spacecrafts used the isotope
      (242)Cm to obtain the chemical composition of the lunar surface material in
      1960s. The Alpha Proton X-ray Spectrometers (APXS) used on several mission to
      Mars (Pathfinder, Mars-96, Mars Exploration Rovers (MER) and on the Mars Science
      Laboratory (MSL), the next mission to Mars in 2011 and on the Rosetta mission to
      a comet) are improved derivatives of the original ASI, complimented with an X-ray
      mode and using the longer lived (244)Cm isotope. (57)Co, (55)Fe and many other
      radioisotopes have been used in several missions carrying XRF and Mossbauer
      instruments. In addition, (238)Pu isotope is exclusively being used in most of
      the space missions for heating and power generation.

PMID- 19850488
TI  - Effect of ploidy levels on the activities of delta(1)-pyrroline-5-carboxylate
      synthetase, superoxide dismutase and peroxidase in Cenchrus species grown under
      water stress.
AB  - The effects of ploidy levels on the activities of delta(1)-pyrroline-5
      carboxylate synthetase (P5CS; EC not assigned), superoxide dismutase (SOD; EC
      1.15.1.1) and guaiacol peroxidase (POX; EC 1.11.1.7), as well as malondialdehyde
      (MDA) and proline contents were studied in two months old plants of Cenchrus
      species. The Cenchrus species represent three ploidy levels: diploid, tetraploid,
      hexaploid and two life spans: annual and perennial. Plants were subjected to
      water stress for 2, 4, 6 and 8 d by withholding water under glasshouse
      conditions. Although the levels of proline increased with the magnitude of water
      stress, the P5CS activity did not show a corresponding increase in all species.
      Peroxidase and superoxide dismutase activities showed an increase or steady state
      in the early phase of drought and then declined with the further increase in the
      magnitude of water stress, indicating differing behaviors of species towards
      drought tolerance. Under drought, diploid Cenchrus species had a higher POX
      activity, MDA accumulation and lower proline content than tetraploid species.
      Lower POX and higher P5CS activities and proline contents, however, were observed
      in hexaploid and tetraploid species. Taken together, our findings suggest that
      diploid species have a less efficient antioxidant system to scavenge reactive
      oxygen species than tetra and hexaploid Cenchrus. This may result in a
      corresponding variability in growth and persistence under natural grasslands. The
      study also paves the way for investigations on the molecular events associated
      with drought in Cenchrus species differing in ploidy and life span.

PMID- 19850489
TI  - Hammock mitral valve and modified Paneth plasty.

PMID- 19850490
TI  - Warm versus cold cardioplegia for heart surgery: a meta-analysis.
AB  - Much controversy persists regarding the optimal techniques for myocardial
      protection during heart surgery. Numerous studies have compared warm cardioplegia
      with cold cardioplegia for myocardial preservation, but the outcomes were
      inconclusive. The aim of this meta-analysis of randomised controlled trials
      (RCTs) was to compare the beneficial and harmful effects of warm and cold
      cardioplegia during heart surgery. Electronic databases and manual
      bibliographical searches were conducted. A meta-analysis of all RCTs comparing
      warm cardioplegia to cold cardioplegia perfusion during cardiac surgery was
      performed. Data for clinical events (in-hospital death, myocardial infarction
      (MI), low output syndrome, postoperative use of intra-aortic balloon pump, stroke
      and atrial fibrillation), postoperative cardiac index, postoperative creatine
      kinase-MB (CK-MB) and cardiac troponin release were extracted, and we summarised
      the combined results of the data of the RCTs as relative risk (RR), with 95%
      confidence intervals. A total of 41 RCTs including 5,879 patients were assessed
      in this study. We found that there was no statistical difference between patients
      receiving warm cardioplegia and cold cardioplegia in the incidences of clinical
      events. Warm cardioplegia was associated with improved postoperative cardiac
      index. CK-MB and cardiac troponin concentrations after surgery were significantly
      lower in the warm group as compared with the cold group. Using warm cardioplegia
      for myocardial protection during heart surgery resulted in similar incidences of
      clinical events, significant improvement in postoperative cardiac index and
      reduction in postoperative enzyme release as compared with cold cardioplegia.

PMID- 19850491
TI  - Does chronic obstructive pulmonary disease affect postoperative quality of life
      in patients undergoing lobectomy for lung cancer? A case-matched study.
AB  - BACKGROUND: The objective of this investigation was to assess the quality of life
      (QoL) before and after pulmonary lobectomy in patients with chronic obstructive
      pulmonary disease (COPD) and to compare these values with a case-matched
      population of patients with normal respiratory function. METHODS: This is an
      observational analysis performed on a prospective dataset of 220 consecutive
      patients submitted to pulmonary lobectomy for lung cancer (2006-2008). Patients
      submitted to extended procedures (chest wall resection and superior sulcus) were
      excluded from the analysis. Pre- and postoperative (3 months) QoL were assessed
      in all patients through the administration of the Short Form 36v2 (SF36v2) health
      survey, a generic QoL instrument assessing eight health physical and mental
      concepts. Propensity score was used to match COPD patients (according to the
      NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria:
      forced expiratory volume in 1s/forced expiratory vital capacity (FEV1/FVC) ratio
      <0.7 and FEV1 <80%) with counterparts without COPD. QoL scales were compared
      between the two matched groups by means of the Mann-Whitney test. RESULTS:
      Propensity score yielded 50 well-matched pairs of patients with and without COPD.
      Compared with non-COPD patients, those with COPD had a threefold higher rate of
      cardiopulmonary morbidity (14 cases vs 5 cases, 28% vs 10%, p=0.04), lower
      reduction in FEV1 (6% vs 13%, p=0.0002), but lower residual postoperative FEV1
      values (62% vs 74%, p<0.0001). Postoperative carbon monoxide lung diffusion
      capacity (DLCO) (69% vs 65%, p=0.1) and VO(2 max) (15.3 ml kg(-1)min(-1) vs 14.3
      ml kg(-1)min(-1)p=0.4) values were similar between the groups. Although most of
      the preoperative and postoperative QoL domains in both groups were reduced
      compared with normal population (<50), we were not able to find differences
      between the groups in any of the preoperative and postoperative physical and
      mental QoL scales. CONCLUSIONS: The evidence of an acceptable QoL in COPD
      patients may help both patients and physicians in the surgical decision-making
      process in the face of high rates of complications.

PMID- 19850492
TI  - Taurolidine in the prevention and therapy of lung metastases.
AB  - OBJECTIVE: During surgery for colon carcinoma, tumour cells may spread into the
      blood and may lead to the development of distant metastases. The most frequent
      sites of metastases are the liver and lungs. A new therapeutic approach is
      required to prevent tumour implantation of freely circulating tumour cells during
      and after surgery and to treat established metastases. The aim of this
      prospective study was to observe the influence of long-term intravenous
      taurolidine on the development of lung metastases after intravenous injection of
      colon adenocarcinoma cells. METHODS: Tumour cells (DHD/K12/TRb colon
      adenocarcinoma cell line, 1 x 10(6) cells) were injected into the right vena
      jugularis interna of BDIX rats. The animals (n=13) were randomised into three
      groups: group 1: tumour cell implantation without taurolidine application
      (control group); group 2: tumour cell implantation and simultaneous start of the
      taurolidine injection through osmotic pump, removal of the osmotic pump on day 7;
      group 3: tumour cell implantation on day 0 and start of the taurolidine injection
      through osmotic pump on day 14. RESULTS: In the taurolidine groups, the number
      and size of lung metastases were significantly lower compared to the control
      group (p=0.018; p=0.018 and p=0.036; p=0.018). Although the results of the
      intravenous long-term therapy with taurolidine in group 2 did not reach
      statistical significance in comparison with the results of group 3, a positive
      trend was revealed: The mean number of metastases in group 2 was 18.2 versus 28.2
      in group 3. CONCLUSIONS: The application of taurolidine tends to prevent the
      development of lung metastases. Furthermore, taurolidine seems to reduce
      established lung metastases in this in vivo model. Taurolidine may offer
      additional therapeutic options in patients with colon adenocarcinoma.

PMID- 19850493
TI  - Thoracomyoplasty. Editorial comment.

PMID- 19850494
TI  - Non-Hodgkin's lymphoma presenting as an isolated soft-tissue chest wall mass.

PMID- 19850495
TI  - MAZIE: a mass and charge inference engine to enhance database searching of tandem
      mass spectra.
AB  - Peptide sequence identification using tandem mass spectroscopy remains a major
      challenge for complex proteomic studies. Peptide matching algorithms require the
      accurate determination of both the mass and charge of the precursor ion and
      accommodate uncertainties in these properties by using a wide precursor mass
      tolerance and by testing, for each spectrum, several possible candidate charges.
      Using a data acquisition strategy that includes obtaining narrow mass-range MS(1)
      "zoom" scans, we describe here a post-acquisition algorithm dubbed mass and
      charge (Z) inference engine (MAZIE), which accurately determines the charge and
      monoisotopic mass of precursor ions on a low-resolution Thermo LTQ-XL mass
      spectrometer. This is achieved by examining the isotopic distribution obtained in
      the preceding MS(1) zoom spectrum and comparing to theoretical distributions for
      candidate charge states from +1 to +4. MAZIE then writes modified data files with
      the corrected monoisotopic mass and charge. We have validated MAZIE results by
      comparing the sequence search results obtained with the MAZIE-generated data
      files to results using the unmodified data files. Using two different search
      algorithms and a false discovery rate filter, we found that MAZIE-interpreted
      data resulted in 80% (using SEQUEST) and 30% (using OMSSA) more high-confidence
      sequence identifications. Analyses of these results indicate that the accurate
      determination of the precursor ion mass greatly facilitates the ability to
      differentiate between true and false positive matches, while the determination of
      the precursor ion charge reduces the overall search time but does not
      significantly reduce the ambiguity of interpreting the search results. MAZIE is
      distributed as an open-source PERL script.

PMID- 19850496
TI  - Analysis of arginine and lysine methylation utilizing peptide separations at
      neutral pH and electron transfer dissociation mass spectrometry.
AB  - Arginine and lysine methylation are widespread protein post-translational
      modifications. Peptides containing these modifications are difficult to retain
      using traditional reversed-phase liquid chromatography because they are
      intrinsically basic/hydrophilic and often fragment poorly during collision
      induced fragmentation (CID). Therefore, they are difficult to analyze using
      standard proteomic workflows. To overcome these caveats, we performed peptide
      separations at neutral pH, resulting in increased retention of the
      hydrophilic/basic methylated peptides before identification using MS/MS.
      Alternatively trifluoroacetic acid (TFA) was used for increased trapping of
      methylated peptides. Electron-transfer dissociation (ETD) mass spectrometry was
      then used to identify and characterize methylated residues. In contrast to
      previous reports utilizing ETD for arginine methylation, we observed significant
      amount of side-chain fragmentation. Using heavy methyl stable isotope labeling
      with amino acids in cell culture it was shown that, similar to CID, a loss of
      monomethylamine or dimethylamine from the arginine methylated side-chain during
      ETD can be used as a diagnostic to determine the type of arginine methylation.
      CID of lysine methylated peptides does not lead to significant neutral losses,
      but ETD is still beneficial because of the high charge states of such peptides.
      The developed LC MS/MS methods were successfully applied to tryptic digests of a
      number of methylated proteins, including splicing factor proline-glutamine-rich
      protein (SFPQ), RNA and export factor-binding protein 2 (REF2-I) and Sul7D,
      demonstrating significant advantages over traditional LC MS/MS approaches.

PMID- 19850497
TI  - An annual vaccine: seasonal influenza.
AB  - The accelerated development process for annual vaccines such as seasonal
      influenza presents unique challenges for the evaluation of vaccine stability.
      Real-time real-condition studies provide limited information at the time of
      registration, while regulators seek evidence that the current vaccine will
      perform satisfactorily in the field. Participants in the IABS Workshop on
      Stability Evaluation of Vaccines, a Life Cycle Approach, were offered a case
      study from the development of the 2007 influenza vaccine. The case study was
      introduced with preliminary data from the long-term study, as well as results
      from the completed year long study. The manufacturer also offered a proposed
      protocol for stability evaluation of vaccines developed in subsequent seasons.
      Participants were asked to answer a series of questions posed by the regulator,
      and critique the proposed stability protocol according to the principles
      described during the workshop.

PMID- 19850498
TI  - Reliability and precision of EMG in leg, torso, and arm muscles during running.
AB  - Changes in electromyographic (EMG) parameters are used to evaluate timing,
      amplitude, and fatigue of muscle actions during movement. Little published data
      describe the reliability and precision of multiple EMG parameters, how these
      parameters compare to one another, and how these parameters vary between muscles.
      The purpose of this study was to determine the reliability and precision of four
      EMG parameters recorded from the legs, torso, and arm muscles during running.
      Fifteen well-trained male runners performed moderate-intensity treadmill running
      while EMG data were collected from thirteen muscles. Integrated EMG (iEMG), root
      mean square EMG (RMS), maximum M-wave, and median power frequency (MPF) were
      calculated for 25 consecutive strides. Intra-class correlation coefficients (ICC)
      and standard error of measurement (SEM) for each parameter were calculated for
      each muscle. Seven muscles displayed good reliability (ICC>0.80) for all
      parameters studied. MPF was the most reliable variable, with 12 muscles having
      ICC>0.80 and <6% normalized SEM. Reliability and precision differed between
      muscles of similar function and anatomic region. These data emphasize the need
      for researchers and clinicians to have reliability and precision measures for all
      parameters of each muscle, and demonstrates that generalizations must be used
      cautiously when interpreting EMG data collected during running.

PMID- 19850499
TI  - Effects of bluetongue virus infection on sperm quality in bulls: A preliminary
      report.
AB  - During the recent bluetongue virus (BTV) outbreak in Germany, semen quality in
      bulls naturally infected with BTV-serotype 8 was evaluated. Bluetongue status was
      assessed by both serology and polymerase chain reaction (PCR). Six bulls became
      BTV-PCR positive between September and November 2007 without showing clinical
      signs. Between April and May 2008, all six bulls were PCR negative but remained
      seropositive. Semen data from non-infected test bulls recorded between 2006 and
      2007 were matched for season and age and used as controls. BTV-8 infection had no
      effect on sperm volume and concentration, but reduced sperm motility was seen
      after thawing (January-August 2008: 44.1 +/- 12.7% vs. 58.0 +/- 7.9% in the
      uninfected bulls; P < 0.001). Malformed sperm in both in fresh and thawed semen
      from BTV-positive animals was above the 20% permitted maximal limit from December
      2007 to February 2008. Infection with BTV-8 transiently impaired semen quality in
      bulls.

PMID- 19850500
TI  - Determination of the stiffness of the equine cervical spine.
AB  - This aim of this study was to test the hypothesis that the stiffness of the
      equine cervical spine depends on the direction of force applied and on spinal
      position. Muscles and nuchal ligament were removed from the cervical spines of 17
      horses that were without a history of cervical or neurological disease. The
      cervical spines were then flexed/extended dorsoventrally (with the spine straight
      and with the occiput rotated 30 degrees  against T1) and laterolaterally. Mean
      dorsoventral stiffness was 297 N/m (+/- 135) in flexion, 1347 N/m (+/- 2083) in
      extension, 421 N/m (+/- 164) in lateral flexion, 279 N/m (+/- 93) in rotated
      flexion, and 386 N/m (+/- 191) in rotated extension. There was a positive
      correlation between the length of cervical spine and stiffness for dorsoventral
      flexion (r = 0.63; P < 0.01) and extension (r = 0.53; P < 0.05). The stiffness of
      the equine cervical spine depended on the direction of the loading and was 2-7
      times less than thoracolumbar stiffness in horses.

PMID- 19850501
TI  - The efficacy of vagal nerve stimulation in children with pharmacoresistant
      epilepsy: practical experience at a Turkish tertiary referral center.
AB  - BACKGROUND: Vagus nerve stimulation (VNS) is an effective therapy for
      pharmacoresistant epilepsy. Nevertheless, information regarding the long-term
      outcome of VNS in children is limited. AIM: To describe the long-term outcome of
      VNS in patients with pharmacoresistant epilepsy treated at the Gazi University
      Medical Faculty Epilepsy Center, Turkey. PATIENTS AND METHODS: The study included
      24 patients - all younger than 18 years of age (mean age: 14.31 years). Median
      age at the time of VNS device implantation was 11 years. Median age at onset of
      epilepsy was 21 months and median duration of epilepsy was 126 months. All the
      patients' seizures were intractable with antiepileptic drug treatment and all had
      been treated with an average of 6+/-2 antiepileptic medications. In all, 12
      patients had secondary generalized seizures and 12 had partial seizures. Because
      this was a retrospective open study, the number of seizures could not be
      enumerated in most of these cases. RESULTS: The only factor that was associated
      with seizure reduction was duration of follow-up. Age at seizure onset and age at
      VNS device implantation were not associated with seizure reduction. The
      difference in seizure reduction between patients >12 years of age and patients
      <12 years of age was not significant. Mean percentage of seizure reduction after
      6 months-7 years of treatment was, respectively, 22.5% (n=24) (6th month), 32%
      (n=20) (1st year), 42% (n=16) (2nd year), 50.45% (n=11) (3rd year), 52% (n=10)
      (4th year), 60% (n=8) (5th year), 61.25% (n=8) (6th year), and 61.6% (n=6) (7th
      year). The positive effect of VNS persisted throughout the follow-up period.
      CONCLUSIONS: Although it is an expensive method, VNS is an effective treatment
      method. This series shows the necessity of long-term follow-up series for
      understanding the efficacy and advantages of VNS. Prospective, long-term double
      blind studies with large samples are needed to confirm the present study's
      findings.

PMID- 19850502
TI  - Psychosocial adjustment in siblings of young people with Duchenne muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a progressive, impairing, life-limiting
      disorder of childhood. Little is known about how siblings adapt to this. The aim
      of this study is to document psychosocial adjustment in siblings of patients with
      DMD. Healthy siblings (11-18 years old) of young people with DMD attending a
      specialist paediatric centre and their parent/main carer took part. Parents,
      siblings and teachers completed a battery of questionnaires: (i) to assess
      psychiatric risk the Strengths and Difficulties Questionnaire (SDQ), General
      Health Questionnaire (GHQ), Hospital Anxiety and Depression Scale (HADS); (ii) to
      measure general wellbeing: SF-36; (iii) to document DMD illness disability:
      Functional Disability Inventory (FDI); (iv) to assess family function and life
      stresses for the unaffected sibling: Family Assessment Device (FAD), Family
      Burden Interview Schedule and Life Events Checklist. Forty six/77 eligible
      siblings (24 females/22 males); (mean age 14 years (SD 2.3)) took part. Although
      their mean psychological functioning and wellbeing questionnaire scores were
      comparable to normative data, there was a trend for more siblings scoring at high
      risk for psychological (mainly emotional) problems. Weak/moderate associations
      with psychological symptoms in siblings varied according to informant and
      included the following factors: closeness in age to the affected sibling; older
      sibling age; extent of wheelchair use, burden of illness on family interactions,
      and siblings reporting high impact of illness on their lives. Psychological
      symptoms were also associated with less sibling involvement in patient care, with
      broader psychosocial and family disadvantage and with life stresses. Siblings
      have an increased risk for emotional problems, which appears influenced by
      specific illness factors.

PMID- 19850503
TI  - Pharmacophore and QSAR modeling of estrogen receptor beta ligands and subsequent
      validation and in silico search for new hits.
AB  - The pharmacophoric space of estrogen receptor beta (ERbeta) was explored using a
      set of 119 known ligands. Subsequently, genetic algorithm and multiple linear
      regression analysis were employed to select optimal combinations of
      pharmacophoric models and physicochemical descriptors in self-consistent and
      predictive quantitative structure-activity relationships (QSARs) (r(96)(2)=0.79
      0.83, F-statistic=40.96-36.20, r(LOO)(2)=0.74-0.76 and r(PRESS)(2) against 23
      external compounds=0.54-0.56, respectively). Four binding hypotheses emerged in
      two optimal QSAR equations suggesting the existence of distinct binding modes
      accessible to ligands within ERbeta binding pocket. The close similarity among
      the resulting pharmacophores prompted us to merge them in two hybrid models. The
      hybrid pharmacophores illustrated superior receiver operator characteristic
      curves (ROCs) and closely resembled binding interactions suggested by docking
      experiments. The resulting models and associated QSAR equations were employed to
      screen the national cancer institute (NCI) list of compounds and an in house
      built database of known drugs and agrochemicals to search for new ERbeta ligands.

PMID- 19850504
TI  - [The controversy Cajal-Golgi: Stockholm, 1906].
AB  - Stockholm, December 11th, 1906. The Nobel committee has just crowned the
      respective works of the Spaniard Cajal and the Italian Golgi on the nervous
      system. But the ceremony turns into a drama: during its conference, Golgi
      violently attacks his colleague, creating a controversy with deep repercussions
      between "reticulists" and "neuronists".

PMID- 19850505
TI  - Sonochemical synthesis of liquid-encapsulated lysozyme microspheres.
AB  - Liquid-encapsulated lysozyme microspheres were successfully synthesized using a
      sonochemical method. The encapsulation of four different liquids, namely,
      sunflower oil, tetradecane, dodecane and perfluorohexane on the formation,
      stability and morphology of the lysozyme microspheres was studied. Among the four
      different liquids used for encapsulation, perfluorohexane-filled microspheres
      were found to be most stable in the dried state with a narrow size distribution.
      In order to explore the possibility of encapsulating biofunctional molecules
      (e.g., drugs) within these microspheres, liquids containing a fluorescent dye
      (Nile red) were encapsulated and the ultrasound-induced release of these dye
      loaded liquids was studied. The fluorescence data for the liquid-filled lysozyme
      microspheres demonstrated the potential use of the sonochemical technique for
      synthesizing these "vehicles" for the encapsulation and the controlled delivery
      of dyes, flavours, fragrances or drugs.

PMID- 19850506
TI  - Phase transformation of nanostructured titanium dioxide from anatase-to-rutile
      via combined ultrasound assisted sol-gel technique.
AB  - An effort was made to synthesize nanostructured TiO(2) via sol-gel technique to
      obtain a 100% rutile polymorph of nanostructured TiO(2). The sol-gel synthesis
      technique was suitably modified by incorporating ultrasound to study the effect
      of cavitation on the phase transformation, crystallite size, crystallinity and
      morphological (scanning electron microscopy) properties of the obtained nano
      TiO(2). It was observed that using ultrasound, yield of the nano-TiO(2) was
      improved from 86.35% to 95.078%. The phase transformation of anatase-to-rutile of
      TiO(2) was studied for both (ultrasound assisted and conventional) the processes.
      Complete phase transformation of the TiO(2) was observed as expected with and
      without the use of ultrasound but the marked reduction in the required
      calcination temperature for obtaining 100% phase transformation with ultrasound
      was the major achievement in the present study, leading to 70% energy savings
      during calcination.

PMID- 19850507
TI  - A nonlinear identification method to study effective connectivity in functional
      MRI.
AB  - In this paper we propose a novel approach for characterizing effective
      connectivity in functional magnetic resonance imaging (fMRI) data. Unlike most
      other methods, our approach is nonlinear and does not rely on a priori
      specification of a model that contains structural information of neuronal
      populations. Instead, it relies on a nonlinear autoregressive exogenous model and
      nonlinear system identification theory; the model's nonlinear connectivities are
      determined using a least squares method. A statistical test was developed to
      quantify the significance of the influence that regions exert on one another. We
      compared this approach with a linear method and applied it to the human visual
      cortex network. Results show that this method can be used to model nonlinear
      interaction between different regions for fMRI data.

PMID- 19850508
TI  - Division plane determination during plant somatic cytokinesis.
AB  - Division plane determination in plant cells involves the transformation of the
      cortical microtubular array into a preprophase band (PPB) with the nucleus
      anchored at the center. This likely occurs through polarity cues controlling
      proteins affecting cytoskeletal dynamics. Crosstalk with cell cycle machinery
      should assure that this happens in concert with cell cycle progression. Before
      PPB breakdown, targeted deposition of factors at the position of the PPB
      translates this position into a signal which remains present throughout
      cytokinesis and directs the centrifugal growing cell plate to the correct
      cortical position. Anchoring and maturation of the cell plate ultimately divides
      the two daughter cells. This review aims to provide an up-to-date overview of the
      mechanisms and molecular players in division plane determination in plant somatic
      cytokinesis.

PMID- 19850509
TI  - Receptor endocytosis and signaling in plants.
AB  - The emerging complexity of plant endocytic systems puts it on a par with their
      animal counterparts, reflecting an essential role in signal transduction. The
      endocytic machinery regulates the space and the time of signal transduction and
      processing in the cell. Plants possess numerous cell surface receptor-like
      kinases (RLKs) (more than 600 members in Arabidopsis thaliana and 1100 in rice),
      a trend attributed to their indeterminate mode of growth, the absence of cell
      migration, and the need for adaptation towards the environment. Thus, plants
      would require a robust and highly plastic endocytic system in order to integrate
      multiple signaling cues from neighboring cells as well as the environment.
      Although a comprehensive understanding of how plant endocytosis impacts signaling
      pathways is still lacking, experimental evidence suggests that both plant and
      animal endosomal systems extensively control signaling.

PMID- 19850510
TI  - The molecular basis of cytokinin function.
AB  - Cytokinins are a class of phytohormones that regulate a wide variety of
      physiological and developmental processes such as shoot and root growth.
      Cytokinin signaling relies on a phosphorelay mechanism similar to the prokaryotic
      two-component system. Although the principal components mediating this cascade
      have been identified, only recently have we begun to understand the molecular
      basis of cytokinin action. For example cytokinins control cell differentiation
      rate during root meristem development by suppressing both auxin signaling and
      transport, whereas at early stages of embryo development auxin counteracts
      cytokinin signaling to establish the embryonic root stem-cell niche. The
      antagonistic interaction between cytokinins and auxin seems to also occur in
      other developmental processes, such as lateral root emergence and leaf
      initiation.

PMID- 19850511
TI  - Synthesis of new heterometallic macromolecules: their DNA binding, cleavage
      activity and in vitro model electrochemotherapy study.
AB  - The homodinuclear C(16)H(30)N(8)O(5)Sn(2)Cl(4) (1), heterotetranuclear
      C(16)H(38)N(8)O(9)Sn(2)Cu(2)Cl(8) (2) and C(16)H(38)N(8)O(9)Sn(2)Mn(2)Cl(8) (3)
      macrocyclic complexes were synthesized and characterized by elemental analysis,
      spectroscopic techniques and molar conductance measurements. The interaction
      studies of 1-3 with calf thymus DNA (CT-DNA) were carried out by UV-vis
      titration, fluorescence, cyclic voltammetry and viscosity measurements. These
      results were further authenticated by carrying out interaction studies of 1-3
      with plasmid pBR322 DNA employing gel electrophoresis. To overcome the dose
      resistance, auto toxicity of the drugs, a model study based on
      electrochemotherapy (ECT) was carried out and the results were compared in the
      presence and in the absence of the applied electrical potential.

PMID- 19850512
TI  - Ortho effects on the change in electronic absorption spectrum of pyridinium salts
      of saturated bromohydrocarbon.
AB  - The quaterisation process of 1,2-dibromoethane and pyridine is in situ traced by
      electronic absorption spectrum. Two absorption peaks, induced by mono- and bis
      pyridinium salt of 1,2-dibromoethane, appear at 429 nm and 313 nm, respectively.
      To explain the phenomena, several kinds of alkyl bromides with special structures
      were selected and compared by experimental measurement and theoretical
      calculation. The results indicate that for mono-pyridinium salt of 1,2
      dibromoethane, the electron donor property of ortho-bromine group increases the
      electron cloud density of the carbon atom associated with pyridinium cation,
      which induces red-shift of absorption wavelength.

PMID- 19850513
TI  - Experimental and calculation aspects of vibrational spectra and optimized
      geometry of 2,3,4-tri-fluoro-benzoic acid dimer.
AB  - Raman and FTIR spectra for 2,3,4-tri-fluoro-benzoic acid molecules have been
      recorded in the regions 50-4000 cm(-1) and 400-4000 cm(-1) respectively. The
      geometrical parameters have been optimized in both the monomeric and dimeric
      forms while vibrational frequencies have been calculated in optimum state in the
      dimeric form by employing DFT method. SQM force fields have also been used to
      calculate potential energy distributions in order to make conspicuous vibrational
      assignments. Raman activities calculated by DFT method have been converted to the
      corresponding Raman intensities using Raman scattering theory. Optimized
      geometries of the molecule have been interpreted and compared with the earlier
      reported experimental values for benzoic acid and some mono and di-fluorinated
      benzoic acids. Some of the vibrational frequencies of the title molecule are
      effected upon profusely with the fluorine substitutions in comparison to benzoic
      acid and these differences have been interpreted. The strong doubly hydrogen
      bonded interface of the dimerized system is well demonstrated by the red shift in
      OH stretching frequency concomitant with the elongation of bond length.

PMID- 19850514
TI  - Mechanisms involved in the conduction of anterior temporal epileptiform
      discharges to the scalp.
AB  - OBJECTIVE: To evaluate the mechanisms involved in the conduction to the scalp of
      anterior temporal epileptiform discharges in temporal lobe epilepsy. METHODS:
      During electroencephalographic recordings extra electrodes were applied around
      the eyes and on the cheeks in 13 patients with anterior temporal discharges. The
      amplitude of at least 34 discharges per patient was compared. RESULTS: Five
      hundred and twenty epileptiform discharges were studied. Among standard
      electrodes, most discharges from all patients were maximal at anterior temporal
      electrodes. They were always also seen over the ipsilateral outer canthus and
      inferior orbital electrodes with similar amplitudes, and with lower amplitudes at
      other ipsilateral facial electrodes (67.7-57.6%). Ipsilateral cheek and mid
      temporal electrodes showed amplitudes within similar range (66.3-67.7%) despite
      being at different distance from the temporal lobes. At least 40% of discharges
      were also recorded by facial electrodes contralaterally to the hemisphere where
      discharges were largest ('cross over') with no clear latency difference.
      CONCLUSIONS: The topography of anterior temporal discharges is most readily
      explained by volume conduction through high conductivity skull foramina.
      SIGNIFICANCE: The role of skull holes should be incorporated in EEG and possibly
      in MEG source localisation models and additional facial electrodes can be useful
      in the evaluation of bitemporal discharges in temporal lobe epilepsy.

PMID- 19850515
TI  - Segmental evaluation of the peripheral nerve using tibial nerve SEPs for the
      diagnosis of CIDP.
AB  - OBJECTIVE: SEPs can evaluate the proximal portion of the peripheral nerve,
      including the nerve root, which is preferentially involved in chronic
      inflammatory demyelinating polyradiculoneuropathy (CIDP). We retrospectively
      investigated the utility of tibial nerve SEPs for the diagnosis of CIDP. METHODS:
      Subjects were 12 clinically-defined CIDP patients and 17 patients with diabetic
      polyneuropathy (DPN). We segmentally evaluated the entire peripheral nerve using
      the N8, P15, and N21 components. We defined findings suggestive of proximal
      dominant involvement (proximal-dominant findings), and investigated their
      frequency in both groups. RESULTS: Ten out of 12 CIDP patients showed at least
      one of the proximal-dominant findings, whereas none of the DPN patients did, when
      appropriate parameters were selected. The sensitivity was higher than
      conventional electrodiagnostic criteria such as the European Federation of
      Neurological Societies/Peripheral Nerve Societies criteria (definite in 8/12).
      Both a proximal-dominant involvement in CIDP patients and a distal-dominant
      involvement in DPN patients were evident by the Z-score plots. CONCLUSIONS:
      Tibial nerve SEPs were highly sensitive and specific, at least in comparison with
      DPN, measures for the diagnosis of CIDP. SIGNIFICANCE: Segmental evaluation of
      the peripheral nerve using tibial nerve SEPs is expected as a promising tool to
      document proximal-dominant involvement in CIDP.

PMID- 19850516
TI  - Innate antimicrobial host defense in small intestinal Crohn's disease.
AB  - Paneth cells (PCs) are specialized epithelial cells predominantly found in the
      small intestinal crypts of Lieberkuehn. They produce different broad spectrum
      antimicrobial peptides most abundantly the alpha-defensins HD-5 and -6 (DEFA5 und
      DEFA6). Both these PC products show a specific reduction in small intestinal
      Crohn's disease (CD) - a form of inflammatory bowel disease (IBD). Their decrease
      is independent of current inflammation and an association with a NOD2 frameshift
      mutation has been demonstrated. More recently, another independent and even more
      frequent mechanism has been found which is linked to diminished levels of the Wnt
      pathway transcription factor TCF7L2 (also known as TCF4). Besides regulating the
      expression of HD-5 and HD-6 as TCF4 target genes, the Wnt pathway also
      orchestrates Paneth cell differentiation and maturation and controls stem cell
      maintenance in the small intestine. Besides NOD2 (which is predominantly
      expressed in PC) and ATG16L1 (inter alia important in the exocytosis of PC
      products), TCF4 is the third gene which is associated with small intestinal CD
      and Paneth cell antimicrobial function. Thus, Paneth cells seem to be key player
      emphazising a paramount importance of antimicrobial host defense in small
      intestinal CD pathogenesis.

PMID- 19850517
TI  - Genetic diversity of O157:H7 and non-O157 verocytotoxigenic Escherichia coli from
      Argentina inferred from multiple-locus variable-number tandem repeat analysis
      (MLVA).
AB  - Although serotype O157:H7 has been implicated in most cases of haemolytic-uraemic
      syndrome (HUS), there is growing concern about non-O157 serotypes of
      verocytotoxigenic Escherichia coli (VTEC). Multiple-locus variable-number tandem
      repeat analysis (MLVA) has been focused on the specific typing of O157:H7
      isolates, but recently, a generic MLVA assay for E. coli and Shigella has been
      developed. We performed a study of the polymorphism in 7 generic VNTR loci both
      in VTEC O157:H7 and non-O157 isolates from Argentina, in order to asses the
      ability of the method to type this group of isolates and to get insight into
      their genetic diversity. Sixty-four isolates from cattle, patients with
      diarrhoea, and contaminated food belonging to 8 different serotypes were studied.
      All of them could be typed by this method and revealed 41 different MLVA
      genotypes. The MLVA dendrogram showed 2 main clusters which corresponded to
      O157:H7 and non-O157, respectively. Our results confirm the suitability of this
      MLVA method for analyzing VTEC isolates belonging to several serotypes, both
      O157:H7 as well as non-O157, highlight the genetic variability of the O157:H7
      serotype and the need of additional research in order to find more VNTR loci that
      could allow a higher discrimination among non-O157 VTEC.

PMID- 19850518
TI  - Identifying symmetry in running gait using a single inertial sensor.
AB  - Running gait has been shown to alter due to changes in intensity. It was
      hypothesised that a sacral mounted single inertial sensor could identify the
      centre of mass (COM) vertical accelerations. This study aimed to validate this
      new technique against a criterion measure and to determine the influence of
      changes in running intensity on COM vertical acceleration and the symmetry of COM
      vertical acceleration between left and right steps. Ten athletes ran for 5min at
      their self-selected pace, plus 1km/h above and below this velocity. Validity of
      the single inertial sensor was determined by comparing COM vertical acceleration
      against that measured with a six-camera infrared system. Large correlation
      (r=0.96), a small typical error of estimate (1.84), and mean bias (0.02) were
      found between the two systems. The greatest magnitude in COM vertical
      acceleration occurred at the slowest running pace and decreased as pace
      increased. Sixty percent of the athletes exhibited asymmetry during at least one
      running pace; 30% were asymmetrical across all three velocities. While
      significant changes in COM vertical acceleration occurred between the different
      running velocities, this did not always result in a change in symmetry. This
      study found that a single inertial sensor can be used as a valid means of
      measuring COM vertical acceleration. This technique can detect changes in the COM
      vertical acceleration that may change with running velocity. Gait symmetry (using
      COM vertical acceleration) during running was also quantified using the inertial
      sensor.

PMID- 19850519
TI  - MCT1 genetic polymorphism influence in high intensity circuit training: a pilot
      study.
AB  - Monocarboxylate Transporter 1 (MCT1) mediates the transport of the main fraction
      of lactate across the sarcolemma. A common polymorphic MCT1 variant has been
      identified, but its role in high intensity exercise performance has not been
      defined. We investigated the influence of MCT1 A1470T polymorphism (rs1049434) on
      lactate accumulation after high intensity circuit training. Ten men aged 20-26
      performed three controlled circuit training (CWT) sessions at 60%, 70%, and 80%
      of the 15 repetition maximum (15RM), in non-consecutive days. CWT included three
      sets of a circuit of eight exercises, obtaining lactate measurements immediately
      after each set had been completed. Two independent variables were analysed: MTC1
      genotypes according to the presence or absence of the A1470T polymorphism, and
      the intensity of circuit training. Genotype distributions were in Hardy-Weinberg
      equilibrium, being 30% wild-type, 50% heterozygotes, and 20% mutated homozygotes.
      Mean lactate concentration at 80% of 15RM were significantly higher than the mean
      lactate values at the other intensities (p<0.01). Significant differences between
      genetic groups were found in the lactate accumulation slope at 80% of 15RM
      (p=0.02) and in the maximal lactate concentration reached by all subjects in the
      study (L(max)) (p=0.03). The carriers of the A1470T polymorphism in the MTC1 gene
      seem to exhibit a worse lactate transport capability into the less active muscle
      cells for oxidation.

PMID- 19850520
TI  - Fundamental movement skills among Australian preschool children.
AB  - Early childhood is a critical period for the development of fundamental movement
      skills (FMS). Children who do not master FMS are more likely to experience
      failure in the motor domain and less likely to participate in sport and games
      during childhood and adolescence. Studies among primary school aged children
      report low levels of FMS mastery indicating the need to implement FMS programs
      during the preschool years. Cross-sectional study of 425 children attending
      preschools in the Sydney, Australia in 2008. FMS were assessed using the Test of
      Gross Motor Development-2 including locomotor (run, gallop, hop, horizontal jump)
      and object control (strike, catch, kick overhand throw) skills. Data were
      analysed using linear regression and chi-squared analyses. Total locomotor score
      was higher among girls compared with boys (p<0.00); however only the hop was
      significantly different (p=0.01). Boys had higher total (p<0.00) and individual
      object control scores compared with girls, except the catch (p=0.6). The
      prevalence of mastery differed across each FMS. Girls generally had higher
      mastery of locomotor skills and boys had higher mastery of object control skills.
      These findings highlight the need to provide structured opportunities which
      facilitate children's acquisition of FMS, which may include providing gender
      separated games, equipment and spaces. That mastery of FMS is low in primary
      school children indicates the importance of early intervention programs in
      preschools. Preschools and child care centers hold promise as a key setting for
      implementing FMS programs.

PMID- 19850521
TI  - The role of dimerisation in the cellular trafficking of G-protein-coupled
      receptors.
AB  - The concept that G-protein-coupled receptors can exist as homomeric and/or
      heteromeric complexes is now well established. Despite this, how dynamic such
      interactions are and if this may be modulated during receptor trafficking remain
      topics of debate. Use of endoplasmic reticulum trapping strategies and the
      generation of asymmetric homomers have started to provide information on the
      contribution of protein-protein interactions to receptor maturation, cell surface
      delivery and ligand-mediated endocytosis. Although dimer/oligomer formation
      appears to be essential for cell surface delivery of class A and class C GPCRs,
      this may not be the case for class B receptors.

PMID- 19850522
TI  - An update on P-glycoprotein and drug resistance in Schistosoma mansoni.

PMID- 19850523
TI  - The role of the nurse lecturer in clinical practice in the Republic of Ireland.
AB  - Undergraduate nurse education in Ireland transferred into the third level sector
      in 2002. As a result nurse lecturers are expected to develop a model of clinical
      practice that enables them to be involved in practice and its development while
      maintaining their own nursing expertise and credibility [An Bord Altranais, 2005.
      Requirements and Standards for Nurse Registration Education Programmes, third ed.
      An Bord Altranais, Dublin]. In light of this the researchers set out to explore
      the perceptions of the nurse lecturers' role in clinical practice among nurse
      lecturers, preceptors, clinical nurse managers, clinical placement co-ordinators
      and students. A qualitative research design using focus groups was chosen. A
      purposive sampling strategy generated the sample for 5 in-depth focus group
      interviews with the aforementioned key stakeholders and the data was thematically
      analysed. Five themes emerged which centred on the maintenance of lecturers'
      clinical credibility, the lecturers' role as a resource to clinical staff,
      teaching and assessing students in practice, the value of fostering relationships
      in practice and role duplication. The findings from this study supports the
      anecdotal evidence that confusion exists around the role but more importantly it
      gives the nurse lecturer population guidance on how to develop the role in
      partnership with the various stakeholders in a way that supports the nursing
      students and clinical staff in practice in an effective manner.

PMID- 19850524
TI  - Ultraviolet radiation reduces resistance to Mycobacterium tuberculosis infection
      in BCG-vaccinated guinea pigs.
AB  - Ultraviolet radiation (UVR) in sunlight suppresses anti-microbial immunity and
      may impair vaccine inefficacy. To investigate whether UVR reduces the protective
      efficacy of BCG vaccine, guinea pigs were exposed to a single dose of 5.6, 11.2,
      or 22.5 kJ/m(2) of UVR either 3 days before or 3 or 28 days after BCG vaccination
      and then challenged by the aerosol route with virulent Mycobacterium tuberculosis
      6 weeks later. Pre-challenge skin test responses to purified protein derivative
      (PPD) were significantly reduced in the UV-irradiated animals. Similarly,
      exposure to UVR reduced the proliferation of spleen cells to PPD, altered
      cytokine mRNA expression in spleen and lung digest cells, and increased the
      colony forming units (CFU) in the lungs of M. tuberculosis-infected guinea pigs
      at 5 weeks post-infection. Spleen IFN-gamma, TNF-alpha, IL-10 and IL-12p40 mRNA
      levels were higher when exposed to 5.6 kJ/m(2) UVR, while the levels were
      significantly reduced at 11.2 and 22.5 kJ/m(2). Lung cell IL-10 mRNA expression
      increased at all UVR doses. Thus, UVR exposure a few days before or after BCG
      vaccination at a distant unirradiated site impaired vaccine-induced resistance
      against virulent M. tuberculosis in guinea pigs possibly by altering cytokine
      responses in a UVR dose-dependent manner.

PMID- 19850525
TI  - Stroke treatment with alteplase given 3.0-4.5 h after onset of acute ischaemic
      stroke (ECASS III): additional outcomes and subgroup analysis of a randomised
      controlled trial.
AB  - BACKGROUND: In the European Cooperative Acute Stroke Study III (ECASS III),
      alteplase administered 3.0-4.5 h after the onset of stroke symptoms resulted in a
      significant benefit in the primary endpoint (modified Rankin scale [mRS] score 0
      1) versus placebo, with no difference in mortality between the treatment groups.
      Compared with the 0-3 h window, there was no excess risk of symptomatic
      intracranial haemorrhage. We assessed the usefulness of additional endpoints and
      did subgroup and sensitivity analyses to further investigate the benefit of
      alteplase. METHODS: In a double-blind, multicentre study in Europe, patients with
      acute ischaemic stroke were randomly assigned to intravenous alteplase (0.9 mg/kg
      bodyweight) or placebo. Additional outcome analyses included functional endpoints
      at day 90 or day 30 (mRS 0-1 [day 30], mRS 0-2, Barthel index > or =85, and
      global outcome statistic [day 30]) and treatment response (8-point improvement
      from baseline or 0-1 score on the National Institutes of Health stroke scale
      [NIHSS], and a stratified responder analysis by baseline NIHSS score). The
      subgroup analyses were based on the mRS 0-1 at day 90, symptomatic intracranial
      haemorrhage, and death. Analyses were by intention to treat and per protocol.
      This study is registered with ClinicalTrials.gov, number NCT00153036. FINDINGS:
      418 patients were assigned to alteplase and 403 to placebo. Although not
      significant in every case, all additional endpoints showed at least a clear trend
      in favour of alteplase. Alteplase was effective in various subgroups, including
      older patients (<65 years: odds ratio 1.61, 95% CI 1.05-2.48; > or =65 years:
      1.15, 0.80-1.64; p=0.230), and the effectiveness was independent of the severity
      of stroke at baseline (NIHSS 0-9: 1.28, 0.84-1.96; NIHSS 10-19: 1.16, 0.73-1.84;
      NIHSS > or =20: 2.32, 0.61-8.90; p=0.631). The incidence of symptomatic
      intracranial haemorrhage seemed to be independent of previous antiplatelet drug
      use (no: 2.41, 1.09-5.33; yes: 2.33, 0.79-6.90; p=0.962) and time from onset of
      symptoms to treatment (181-210 min: 1.62, 0.26-10.25; 211-240 min: 1.97, 0.82
      4.76; 241-270 min: 3.15, 1.01-9.79; p=0.761), but not of age dichotomised at 65
      years (<65 years: 0.74, 0.28-1.96; > or =65 years: 5.79, 2.18-15.39; p=0.004).
      INTERPRETATION: Our results support the use of alteplase up to 4.5 h after the
      onset of stroke symptoms across a broad range of subgroups of patients who meet
      the requirements of the European product label but miss the approved treatment
      window of 0-3 h. FUNDING: Boehringer Ingelheim.

PMID- 19850526
TI  - Extending the time window for thrombolytic therapy--primum non tardare.

PMID- 19850527
TI  - Modelling effects of geoengineering options in response to climate change and
      global warming: implications for coral reefs.
AB  - Climate change will have serious effects on the planet and on its ecosystems.
      Currently, mitigation efforts are proving ineffectual in reducing anthropogenic
      CO2 emissions. Coral reefs are the most sensitive ecosystems on the planet to
      climate change, and here we review modelling a number of geoengineering options,
      and their potential influence on coral reefs. There are two categories of
      geoengineering, shortwave solar radiation management and longwave carbon dioxide
      removal. The first set of techniques only reduce some, but not all, effects of
      climate change, while possibly creating other problems. They also do not affect
      CO2 levels and therefore fail to address the wider effects of rising CO2,
      including ocean acidification, important for coral reefs. Solar radiation is
      important to coral growth and survival, and solar radiation management is not in
      general appropriate for this ecosystem. Longwave carbon dioxide removal
      techniques address the root cause of climate change, rising CO2 concentrations,
      they have relatively low uncertainties and risks. They are worthy of further
      research and potential implementation, particularly carbon capture and storage,
      biochar, and afforestation methods, alongside increased mitigation of atmospheric
      CO2 concentrations.

PMID- 19850528
TI  - Teaching children clean intermittent self-catheterization (CISC) in a group
      setting.
AB  - OBJECTIVE: To teach children to perform clean intermittent self-catheterization
      (CISC) at our institution, the nurse practitioner uses a step-by-step approach in
      combination with an instruction model in an outpatient setting. For a small group
      of children the procedure remains difficult to learn. For them, we developed a
      multidisciplinary, group-wise training program. PATIENTS AND METHODS: Small
      groups of children, aged 7-12 years, and their parents consulted our clinic
      during six meetings. The group training was provided by a pediatric urology nurse
      practitioner, physiotherapist and behavioural practitioner. Using a tell/show/do
      method each intervention was instructed group wise. The actual CISC was performed
      individually within a private setting. Elements of the training were: sharing of
      mastery and difficulties with other children/parents, cognitive restructuring to
      enhance understanding and motivation, handling and trying out of devices,
      relaxation as a response to physical stress, and supporting parental guidance.
      RESULTS: The preliminary results of seven children were successful after group
      wise intervention. Children were less anxious and more cooperative. Parents could
      share their difficulties dealing with their child at home and were given
      suggestions to help their children with CISC. CONCLUSION: Group interactions and
      a multidisciplinary approach seems to be of great help in learning CISC for
      selected children.

PMID- 19850529
TI  - Correlation between uroflowmetry parameters and treatment outcome in children
      with dysfunctional voiding.
AB  - PURPOSE: To investigate the correlation between subjective (clinical) treatment
      outcome and objective uroflowmetry parameters and curve pattern in children with
      dysfunctional voiding. METHOD: Seventy-five children were randomly allocated to
      two urotherapy programs. Group A was submitted to standard urotherapy and pelvic
      floor exercises while group B received conservative treatment. Constipation and
      recurrent urinary tract infections (UTIs) were treated in both groups. Selected
      children from both groups received pharmacotherapy (anticholinergics or
      desmopressin). Uroflowmetry with electromyography of the pelvic floor and
      ultrasound post-void residual (PVR) urine volumes were obtained before and at the
      end of the 12-month treatment period. Uroflowmetry findings were stratified into
      two categories based on clinical treatment outcome: 'cured' and 'unchanged'.
      Uroflowmetry findings were compared between categories at the beginning and the
      end of the investigation. RESULTS: Voided volume, average and peak flow rates
      were significantly increased while PVR urine was decreased in children with cured
      urinary incontinence and nocturnal enuresis compared with 'unchanged' category.
      Significant decrease of PVR urine was noted in children with cured UTIs. The
      frequency of a bell-shaped curve was significantly higher compared to other curve
      patterns in children with cured urinary incontinence and UTIs. CONCLUSION: Post
      treatment improvement in clinical symptoms correlated with improvement in
      uroflowmetry parameters and curve pattern. Correction of voiding phase is
      necessary for urinary continence achievement and resolution of UTIs.

PMID- 19850530
TI  - Commentary to "pediatric hemorrhagic cystitis" by Decker DB, Karam JA, Wilcox DT.
      J Pediatr Urol 2009;5:254-264: management of hemorrhagic cystitis in children
      after hematopoietic stem cell transplantation: keep it safe.

PMID- 19850531
TI  - Ovarian tissue cryopreservation and transplantation in cancer patients.
AB  - Advances in the diagnosis and treatment of childhood, adolescent and adult cancer
      have greatly increased the life expectancy of premenopausal women with cancer.
      The ovaries are very sensitive to cytotoxic treatment, especially to alkylating
      agents. The only established method of fertility preservation is embryo
      cryopreservation according to the Ethics Committee of the American Society for
      Reproductive Medicine (2005), but this option requires the patient to be of
      pubertal age, have a partner or use donor sperm and be able to undergo a cycle of
      ovarian stimulation, which is not possible when the chemotherapy has to be
      initiated immediately or when stimulation is contraindicated, according to the
      type of cancer. For patients who need immediate chemotherapy, cryopreservation of
      ovarian tissue is the only possible alternative. This article reports the
      techniques and results of orthotopic transplantation of cryopreserved ovarian
      tissue. Among almost 30 cases reported in the literature, six live births have
      been achieved to date.

PMID- 19850532
TI  - Comparison of anterior cervical fusion after two-level discectomy or single-level
      corpectomy: sagittal alignment, cervical lordosis, graft collapse, and adjacent
      level ossification.
AB  - BACKGROUND CONTEXT: Single-level corpectomy and two-level discectomy with
      anterior cervical plating have been reported to have comparable fusion and
      complication rates. However, there are few large series that have compared the
      two for sagittal alignment, cervical lordosis, graft subsidence, and adjacent
      level ossification. PURPOSE: To determine the differences between these two
      procedures for patients with two-level spondylosis by comparing the pre- and
      postoperative radiographic data. STUDY DESIGN: Retrospective review of
      prospectively collected data in an academic institution. PATIENT SAMPLE: Fifty
      two with a single-level corpectomy and 45 with a two-level anterior cervical
      discectomy and fusion (ACDF). OUTCOME MEASURES: Pre- and postoperative
      radiographic data for sagittal alignment, cervical lordosis, subsidence, and
      adjacent-level ossification. METHODS: We retrospectively reviewed the lateral
      cervical radiographs of patients who had a solid fusion after a single-level
      cervical corpectomy or a two-level ACDF for the treatment of a degenerative
      cervical spondylosis by a surgeon at an academic institution. The choice of the
      operation was dependent on the presence or absence of retrovertebral compression.
      All patients underwent anterior cervical fusion using fibula strut allograft and
      variable-angle screw-plate fixation. None had had prior cervical spine surgery.
      Twenty-five were excluded because of inadequate radiographs and follow-up. There
      were 52 with a single-level corpectomy and 45 with a two-level ACDF. The
      following were analyzed: 1) sagittal alignment (modified method of Toyama); 2)
      cervical lordosis measured by Cobb angles of fusion constructs (fusion Cobb) and
      C2-C7 (C2-C7 Cobb); 3) graft collapse determined by the subsidence of
      anterior/posterior body height of fused segments (anterior/posterior subsidence)
      and the cranial/caudal plate-to-disc distances (cranial/caudal subsidence), and
      the difference between anterior and posterior body height for the fused levels
      (anteroposterior [AP] difference); and 4) the severity of ossification at two
      adjacent levels. RESULTS: The mean durations of follow-up were 23.3+/-6.6
      (corpectomy) and 25.7+/-6.2 (ACDF) months, range 12 to 45 months. There were no
      significant differences between the two groups in sagittal alignment, cervical
      lordosis, graft collapse, and adjacent-level ossification. Graft subsidence and
      loss of cervical lordosis occurred significantly more during the first 6 weeks
      after surgery (all measurements, p<.0001) than after 6 weeks, with no significant
      difference between the two groups. Posterior and caudal end plate subsidence
      significantly progressed after 6 weeks in Group 1 (p=.04, p=.02). The final
      follow-up Cobb angle positively correlated with preoperative and immediate
      postoperative Cobb angles (r=0.437, p<.0001; r=0.727, p<.0001), caudal subsidence
      (r=0.270, p=.008), and the final AP difference (r=0.915, p<.0001) but did not
      correlate with surgery level, preoperative and final sagittal alignments,
      anterior/posterior subsidence, and cranial subsidence. Anterior/posterior
      subsidence was significantly more strongly related with caudal subsidence
      (r=0.607, p<.0001; r=0.424, p<.0001) than cranial (r=0.277, p=.007; r=0.211,
      p=.040) but did not correlate with pre- and postoperative fusion Cobb, and
      preoperative and the last sagittal alignments. CONCLUSIONS: Our data suggest that
      the two procedures yield comparable results in terms of sagittal alignment,
      cervical lordosis, graft subsidence, and adjacent-level ossification. Graft
      subsidence and loss of cervical lordosis appeared to occur mainly during the
      first 6 weeks after surgery. Single-level corpectomy and fusion continued to
      subside at the posterior portion of caudal end plate even after 6 weeks. On the
      other hand, graft subsidence did not correlate with preoperative and final
      postoperative sagittal alignments.

PMID- 19850533
TI  - Modeling study for optimization of skin dose for partial breast irradiation using
      Xoft Axxent electronic brachytherapy applicator.
AB  - PURPOSE: Balloon brachytherapy with the MammoSite system (Hologic Inc., Bedford,
      MA) is a widely used approach for accelerated partial breast irradiation.
      Inherent to this approach, high skin doses can occur if the balloon to skin
      distance is small. This has been associated with late skin toxicity, particularly
      telangiectasia. The Xoft Axxent electronic brachytherapy balloon applicator
      (Xoft, Fremont, CA) is a novel device for accelerated partial breast irradiation.
      It is unique in that it uses an electronic 50-kV source. This source has a
      pronounced anisotropy with constriction of isodose distribution at the proximal
      end of the catheter. This anisotropy can be considered as an advantage to
      optimize skin dose when the cavity to skin distance is small. In this study, we
      simulated various balloon-insertion orientations to optimized skin surface dose.
      METHODS: Breast phantoms were constructed of tissue-equivalent material. Xoft
      Axxent balloon catheters were inserted at a distance of 6mm from the surface. The
      catheter was placed at three different catheter to surface orientations: (1)
      perpendicular to the surface, (2) oblique to the surface (45 degrees), and (3)
      parallel to the surface. Three-dimensional treatment planning was then performed
      using Nucletron's Plato planning system (Nucletron, Columbia, MD). Multiple dwell
      positions were used, and the dose was optimized to the target volume. The target
      volume was defined as volume from the balloon surface to 1-cm distance from the
      balloon surface or to the phantom surface (if less then 1cm from the balloon
      surface). Target volume coverage was compared between plans using dose-volume
      histograms. Surface doses were compared using isodose line distribution and
      surface point doses. Plato planned surface doses were then verified by direct
      measurement using Landauer Dot InLight dosimeters (Landauer, Glenwood, IL).
      RESULTS: Excellent target coverage was obtained for all three catheter
      orientations with a D(95) of > or =95%. Surface dose was lowest for the
      perpendicular orientation with a calculated dose of 99%. The parallel orientation
      had the highest surface dose of 164%. The oblique orientation showed intermediate
      results with a surface dose of 117%. Measured surface doses were reproducible and
      correlated well with calculated values. CONCLUSION: Optimized Xoft Axxent balloon
      catheter orientation using source anisotropy and multiple dwell positions can be
      used to minimize excessive skin dose and yet maintain optimal tumor cavity
      coverage when the cavity to skin distance is small. This has the potential to
      decrease skin late effects and improve cosmetic outcome. Further clinical study
      is warranted.

PMID- 19850534
TI  - An intraoperative real-time sleeved seed technique for permanent prostate
      brachytherapy.
AB  - PURPOSE: To describe a novel technique that integrates customized sleeved seed
      production to reduce seed migration using preloaded needles with real-time
      intraoperative dosimetric planning for patients treated with iodine-125 (I-125)
      permanent prostate seed implants. METHODS AND MATERIALS: Customized seed-spacer
      sequences were calculated for patients in real time based on an intraoperative
      transrectal ultrasound-guided volume study. Using a Fox Chase Cancer Center
      modified Best Iodine-125 seed loader (Best Medical, Springfield, VA), the seeds
      and spacers were inserted into a hollow suture material (sleeve) and then loaded
      into the implant needles. Needles were placed sequentially under transrectal
      ultrasound guidance with sagittal plane visualization of the dropped sleeved
      seeds. RESULTS: This technique was successfully implemented allowing
      intraoperative planning to be combined with real-time sleeved seed production.
      CONCLUSIONS: The use of sleeves for seeds combined with real-time intraoperative
      planning allowed for the intraoperative customization of implants with the
      practical advantages of linked seeds.

PMID- 19850535
TI  - The role of dose escalation with intracavitary brachytherapy in the treatment of
      localized CNS malignancies: outcomes and toxicities of a prospective study.
AB  - PURPOSE: This single-institution prospective study was designed to investigate
      the feasibility and safety of dose escalation with GliaSite (Proxima Therapeutics
      Inc., Alpharetta, GA) brachytherapy for the treatment of patients with newly
      diagnosed and recurrent central nervous system (CNS) tumors after neurosurgical
      resection. We now report mature results of this trial, its outcomes, and a
      toxicity profile. METHODS AND MATERIALS: Ten adult consecutive patients with
      recurrent and newly diagnosed CNS malignancies underwent GliaSite brachytherapy
      after maximally safe neurosurgical resection between 2004 and 2007. GliaSite
      balloon was placed intraoperatively, and the size was selected so as to conform
      to the surgical cavity. Low-dose-rate radiation was delivered with an aqueous
      solution of organically bound (125)I (Iotrex: sodium 3-((125)I)-iodo-4
      hydroxybenzenesulfonate; Proxima Therapeutics Inc.), introduced into the balloon
      portion of the device via a subcutaneous port. Two to 3 weeks later, the device
      was filled with Iotrex for a median dwell time of 94.3 hours (range, 68.0-120.5
      hours), after which the balloon was explanted. A commercial 3-D planning system
      was used for a detailed analysis of dosimetry. Median dose of 52.0 Gy (range,
      45.0-60.0 Gy) was prescribed 0.5-1.0 cm from the balloon surface. Radiation
      Therapy Oncology Group (RTOG) criteria were used to assess acute and long-term
      toxicities associated with this technique. Followup was assessed with MRI scans
      and was available on all enrolled patients. RESULTS: Median followup for
      surviving patients was 38 months (range, 18-57 months). Mean size of GliaSite
      balloon was 3.4 cm (range, 2.0-4.0 cm). Mean volume of filling was 19.0 cc
      (range, 4.0-35.0 cc). Median activity of Iotrex was 301.6 mCi (range, 95.0-515.4
      mCi). Median survival was 14.0 months for the entire cohort after the treatment
      with the GliaSite device. Of our cohort, 6/10 (60%) patients sustained recurrence
      (20% local and 40% distant). Median time to recurrence after treatment with
      GliaSite was 8.0 months, and median time to death after recurrence was 7.5
      months. There were no RTOG Grade 3 or 4 acute or late toxicities. Followup MRI
      imaging did not identify any evidence of radiation necrosis. CONCLUSIONS: Our
      data indicate that treatment with GliaSite balloon brachytherapy is feasible and
      safe, while rendering acceptable local control and minimal acute and long-term
      toxicities for newly diagnosed and recurrent CNS malignancies. These encouraging
      results compel us to embark on testing larger numbers of patients with this
      treatment modality.

PMID- 19850536
TI  - Treatment outcome and toxicity after salvage 125-I implantation for prostate
      cancer recurrences after primary 125-I implantation and external beam
      radiotherapy.
AB  - PURPOSE: To evaluate the outcome and toxicity after salvage iodine-125 (125-I)
      implantation in patients with locally recurrent prostate cancer after primary 125
      I implantation and external beam radiotherapy. METHODS AND MATERIALS:
      Retrospectively, 31 patients were analyzed with pathology-proven local recurrent
      prostate cancer after primary external beam radiotherapy (n=20) or 125-I
      implantation (n=11), and who had undergone salvage 125-I implantation between
      1994 and 2009. For recording biochemical failure rates, the Phoenix definition
      and the American Society for Therapeutic Radiology and Oncology definition were
      applied. Toxicity was scored according to the Common Terminology Criteria for
      Adverse Events version 3.0 (CTCAE v3.0) (Cancer Therapy Evaluation Program,
      National Cancer Institute, National Institutes of Health, Bethesda, MD). RESULTS:
      The mean (+/-standard deviation [SD]) followup was 9 years (+/-4). The freedom
      from biochemical failure after 1 and 5 years' followup were 51% and 20%,
      respectively. Fourteen (45%) patients died of prostate cancer after a mean (+/
      SD) followup of 73 (+/-39) months. Grade 1, 2, or 3 toxicity of the genitourinary
      tract was reported in 29%, 58% and 3% of the patients, respectively, in the acute
      phase, and in 16%, 39%, and 19%, respectively, in the late phase. Grade 1, 2, or
      3 toxicity of the gastrointestinal tract was reported in 45%, 10%, and 0% of the
      patients, respectively, in the acute phase, and in 48%, 3%, and 6%, respectively,
      in the late phase. Grade 4 toxicity of any tract occurred in none of the patients
      in the acute or the late phase. CONCLUSIONS: Freedom from biochemical failure
      after salvage 125-I implantation for locally recurrent prostate cancer after
      radiotherapy is limited, and both genitourinary and gastrointestinal toxicity
      occur frequently.

PMID- 19850537
TI  - PSA bounce after prostate brachytherapy with or without neoadjuvant androgen
      deprivation.
AB  - PURPOSE: To assess the impact of PSA bounce (PB) on biochemical failure (BF) and
      clinical failure (CF) in brachytherapy patients treated with or without
      neoadjuvant androgen deprivation (AD). METHODS AND MATERIALS: From 1987 to 2003,
      691 patients with clinical stage T1-T3N0M0 prostate cancer were treated with
      external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy boost
      (n=407), HDR brachytherapy alone (n=93), or permanent seed implant (n=191). Three
      hundred seventeen patients (46%) received neoadjuvant/adjuvant AD with RT. BF was
      scored using 3 definitions (ASTRO--3 rises, nadir+2 ng/ml, and threshold 3 ng/ml)
      based on current and absolute nadir (AN) methodologies. PB was defined as any
      increase in PSA followed by a decrease to the prior baseline or lower. The median
      followup was 4.0 years. RESULTS: Forty-six patients (7%) experienced CF at 5
      years. PB of >or=0.1, >or=1.0, and >or=2.0 ng/ml at any time after RT occurred in
      330 (48%), 60 (9%), and 22 patients (3%) respectively. The use of an AN
      definition reduced the likelihood of scoring PB as BF across all levels. The
      patients receiving AD experienced significantly longer bounce duration. Bounce
      <1.0 ng/ml showed no association with CF. For bounce >or=1.0 ng/ml, 10%
      demonstrated CF vs. 6% without bounce of this amplitude (p=0.27). Bounces >or=1.0
      ng/ml were more likely to be scored as BFs for definitions based on current nadir
      (3 rises: 20% vs. 13%, nadir+2: 43% vs. 11%, 3 at/after nadir: 57% vs. 12%) than
      those based on AN (3 rises: 8% vs. 10%, nadir+2: 18% vs. 11%, 3 at/after nadir:
      13% vs. 11%). CONCLUSIONS: Bounces >or=1.0 ng/ml are rare after brachytherapy
      with or without neoadjuvant AD, occurring in less than 10% of patients. Low PBs
      have little impact on BF, but as PB amplitude increases, the BF rate increases.
      BF definitions based on AN are less sensitive to PB after brachytherapy.

PMID- 19850538
TI  - Driving restrictions in patients following syncope is difficult for physicians.
AB  - Syncope occurring while driving has obvious implications for personal and public
      safety. In this report, the authors aimed to define the clinical characteristics,
      causes, and prognosis of syncope while driving. Using a case-control design, they
      studied consecutive patients evaluated for syncope from 1996 through 1998 at the
      Mayo Clinic in Rochester, Minnesota. Of 3877 patients identified, 381 (9.8%) had
      syncope while driving (driving group). Compared with the 3496 patients (90.2%)
      who did not have syncope while driving, the driving group was younger (P<0.01)
      and had higher percentages of male patients (P<0.001) and patients with a history
      of any cardiovascular disease (P<0.01) and stroke (P<0.02). Syncope while driving
      was commonly caused by neurally mediated syncope (37.3%) and cardiac arrhythmias
      (11.8%). Long-term survival in the driving group was comparable to that of an age
      and sex-matched cohort from the Minnesota population. Among the driving group,
      syncope recurred in 72 patients, 35 of whom (48.6%) had recurrence >6 months
      after the initial evaluation. Recurrences during driving happened in 10 patients
      in the driving group, 7 of which (70%) were >12 months after the initial
      evaluation. Overall, neurally mediated syncope was the most common type of
      syncope while driving. Their findings about the late recurrences of syncope
      (often >6 months of follow-up) and the overall low incidence of recurrent syncope
      while driving, may inform future recommendations on driving for these patients.

PMID- 19850539
TI  - Comment on 'Isolation and detection of steroids from human urine by molecularly
      imprinted solid-phase extraction and liquid chromatography' by Gadzala-Kopciuch
      et al., J. Chromatogr. B 877 (2009), 1177-1184.

PMID- 19850540
TI  - [N-carbamyl glutamate treatment in hyperammoniemia decompensated propionic
      acidaemia].

PMID- 19850541
TI  - [Fatty liver disease, insulin resistance and adiponectin in an obese pediatric
      population].
AB  - INTRODUCTION: To study the clinical and laboratory relationships of fatty liver
      disease in a group of obese children and to investigate whether circulating
      adiponectin is related to fatty liver disease. PATIENTS AND METHODS: Two hundred
      ninety obese patients (age 4-18 years) were studied. Baseline body mass index
      standard deviation score (BMI-SDS), acanthosis nigricans, blood pressure, plasma
      lipids, uric acid, alanine aminotransferase (ALT) and adiponectin were assessed,
      and a standard oral glucose tolerance test was performed. Insulin resistance (RI)
      was estimated by the homeostasis model assessment (HOMA) and liver steatosis was
      assessed by ultrasound (US). Children were classified as having metabolic
      syndrome if they met three or more of the following criteria: obesity,
      hypertension, hypertriglyceridemia, low HDL-cholesterol and impaired glucose
      metabolism. RESULTS: Fifty-two subjects (18%) had fatty liver by US and 22 (8%)
      had elevated ALT levels (> or =40 U/L). Subjects with steatosis were
      significantly older (12.2+/-2.4 frente a 11.1+/-2.9 yr), heavier (BMI-SDS: 4.5+/
      1.5 frente a 3.8+/-1.3), and more RI (HOMA: 3.7+/-1.5 frente a 2.4+/-1.4), but
      were comparable in gender, pubertal status and racial distribution to those with
      normal US. The prevalence of metabolic syndrome and acanthosis nigricans were
      also higher in the steatosis frente a the normal US group. Serum adiponectin
      concentration was inversely correlated with age, HOMA, ALT and uric acid and
      directly correlated with HDL-cholesterol. In a multiple logistic regression
      analysis, BMI-SDS, HOMA and serum adiponectin, but not age, uric acid or
      triglycerides, were the covariates independently associated with the presence of
      steatosis (odds ratio 1.4 [1.1-1.9]; 1.3 [1.1-1.6] and 0.9 [0.8-0.9],
      respectively). CONCLUSIONS: Obesity and RI are risk factors for liver steatosis
      in children and adolescents. Decreased serum adiponectin is closely and
      independently associated with steatosis.

PMID- 19850542
TI  - [Worsening topiramate-associated headache in a child with migraine with aura].

PMID- 19850543
TI  - Nonchoroidal intraorbital malignant melanoma arising from naevus of Ota.
AB  - A case report of nonchoroidal intraorbital malignant melanoma arising from naevus
      of Ota, in a Caucasian female.

PMID- 19850544
TI  - How to create a natural nasolabial fold during muscle transplantation for the
      treatment of facial paralysis.

PMID- 19850545
TI  - Doppler-derived deformation imaging in unsedated healthy adult dogs.
AB  - OBJECTIVES: To evaluate feasibility, repeatability and reproducibility (R&R) of
      Doppler-derived deformation imaging (DI) in healthy adult dogs. ANIMALS,
      MATERIALS AND METHODS: Forty-nine dogs underwent physical examination, ECG, blood
      pressure measurement and echocardiography. Doppler-derived DI parameters obtained
      from six selected Regions of Interest (ROI) within the left ventricle (LV) were:
      strain (S), systolic strain rate (SSR), strain rate E wave (SRE), and strain rate
      A wave (SRA). The averages of the six ROIs were calculated and labeled avS,
      avSSR, avSRE, and avSRA. Randomly selected dogs underwent two echocardiographic
      studies to evaluate intraoperator (n=14) and interoperator (n=17) variability.
      RESULTS: DI data were obtained in 87.2% of dogs and 77.2% of ROIs. Compared to
      controls, avSSR was significantly reduced in Doberman Pinchers (DP) and it was
      increased in dogs < 30 kg, compared to dogs > 30 kg. The intraoperator
      Coefficient of Variability (CV) for some ROIs was greater than 15% but for
      averaged measurements it was < or = 5.0%. Interoperator CV varied widely but were
      all < 15% for avSSR, avS, and avSRA. CONCLUSIONS: The CV for Doppler-derived DI
      varied widely. Averaging values from multiple ROIs improved R&R. DI may help
      elucidate differences in LV mechanics between canine breeds.

PMID- 19850546
TI  - Plasma N-terminal pro-B-type natriuretic peptide concentration helps to predict
      survival in dogs with symptomatic degenerative mitral valve disease regardless of
      and in combination with the initial clinical status at admission.
AB  - OBJECTIVES: Although mitral valve disease (MVD) is the most common canine heart
      disease, readily available prognostic markers of the disease are still lacking.
      The aim of this study was to evaluate the comparative ability of N-terminal pro-B
      type natriuretic peptide plasma concentration (NT-proBNP) and various
      echocardiographic variables to predict outcome in dogs with MVD. ANIMALS,
      MATERIALS AND METHODS: Seventy-four dogs with ISACHC classes 2 and 3 MVD (Groups
      A and B, respectively) were prospectively recruited. NT-proBNP and several echo
      Doppler variables at inclusion were compared as predictors of outcome at 6 months
      in 54/74 dogs. RESULTS: NT-proBNP was significantly higher in Group B than in
      Group A (P<0.0001), and was the only tested variable significantly different
      between survivor and non-survivor dogs in both groups (P<0.05). In the whole
      canine population, a threshold of 1500 pmol/L could discriminate survivor from
      non-survivor dogs with a sensitivity and specificity of 80% and 73%,
      respectively. When combining ISACHC class with NT-proBNP levels, a cut-off of
      1265 pmol/L was predictive of survival in Group A, whereas the cut-off was 2700
      pmol/L for Group B. CONCLUSIONS: NT-proBNP is correlated with MVD severity and
      could be used in combination with clinical status to predict cardiac outcome.

PMID- 19850547
TI  - Segmentally-arranged cutaneous mucinosis ranging from papulonodules to sclerotic
      pigmented macules.

PMID- 19850549
TI  - Health e-cards as a means of encouraging help seeking for depression among young
      adults: randomized controlled trial.
AB  - BACKGROUND: There is a need to identify interventions that increase help seeking
      for depression among young adults. OBJECTIVE: The aim was to evaluate a brief
      depression information intervention employing health e-cards (personalized emails
      containing links to health information presented on a Web page). METHODS: A
      randomized controlled trial was carried out with 348 19- to 24-year-olds drawn
      from the community. Participants were randomized to receive one of three
      conditions, all of which delivered a short series of health e-cards. Two active
      conditions involved the delivery of depression information designed to increase
      help-seeking behavior and intentions and to improve beliefs and knowledge
      associated with help seeking. A control arm delivered information about general
      health issues unrelated to depression. The primary outcome was help-seeking
      behavior. Secondary outcomes were help-seeking intentions; beliefs about the
      efficacy of depression treatments and help sources; ability to recognize
      depression; knowledge of the help-seeking process; and depressive symptoms. The
      study's primary focus was outcomes relating to formal help seeking (consultation
      with a general practitioner or mental health professional) but also targeted
      behaviors, intentions, and beliefs relating to informal help seeking. RESULTS:
      Relative to the control condition, depression health e-cards were not associated
      with an increase in formal help-seeking behavior, nor were they associated with
      improved beliefs about depression treatments; ability to recognize depression;
      knowledge of the help-seeking process; or depressive symptoms. Depression e-cards
      were associated with improved beliefs about the overall efficacy of formal help
      sources (z = 2.4, P = .02). At post-intervention, participants in all conditions,
      relative to pre-intervention, were more likely to have higher intentions of
      seeking help for depression from a formal help source (t(641) = 5.8, P < .001)
      and were more likely to rate interpersonal psychotherapy as being helpful (z =
      2.0, P = .047). Depression e-cards were not associated with any significant
      changes in informal help-seeking behavior, intentions, or beliefs. CONCLUSIONS:
      The study found no evidence that providing depression information in the form of
      brief e-cards encourages help seeking for depression among young adults.
      Involvement in the study may have been associated with increased help-seeking
      intentions among participants in all conditions, suggesting that mechanisms other
      than depression information may increase help seeking.

PMID- 19850550
TI  - A simulation model to predict the fiscal and public health impact of a change in
      cigarette excise taxes.
AB  - OBJECTIVES: (1) To present a model that predicts changes in cigarette consumption
      and excise revenue in response to excise tax changes, and (2) to demonstrate
      that, if the industry has market power, increases in specific taxes have better
      tobacco control consequences than increases in ad valorem taxes. DESIGN: All
      model parameters are user-determined. The model calculates likely changes in
      cigarette consumption, smoking prevalence and excise tax revenues due to an
      excise tax change. The model is applicable to countries that levy excise tax as
      specific or ad valorem taxes. RESULTS: For a representative low-income or middle
      income country a 20% excise tax increase decreases cigarette consumption and
      industry revenue by 5% and increases excise tax revenues by 14%, if there is no
      change in the net-of-tax price. If the excise tax is levied as a specific tax,
      the industry has an incentive to raise the net-of-tax price, enhancing the
      consumption-reducing impact of the tax increase. If the excise tax is levied as
      an ad valorem tax, the industry has no such incentive. The industry has an
      incentive to reduce the net-of-tax price in response to an ad valorem excise tax
      increase, undermining the public health and fiscal benefits of the tax increase.
      CONCLUSIONS: This paper presents a simple web-based tool that allows policy
      makers and tobacco control advocates to estimate the likely consumption, fiscal
      and mortality impacts of a change in the cigarette excise tax. If a country
      wishes to reduce cigarette consumption by increasing the excise tax, a specific
      tax structure is better than an ad valorem tax structure.

PMID- 19850548
TI  - Plasmacytoid dendritic cells and dermatological disorders: focus on their role in
      autoimmunity and cancer.
AB  - Dendritic cells (DC), considered as immunological sentinels of the organism since
      they are antigen presenting cells, create the link between innate and adaptive
      immunity. DC include myeloid dendritic cells (MDC) and plasmacytoid dendritic
      cells (PDC). The presence of PDC, cells capable of producing large quantities of
      interferon alpha (IFN-alpha) in response to pathogenic agents or danger signals,
      seems to be closely related to pathological conditions. PDC have been observed in
      inflammatory immunoallergic dermatological disorders, in malignant cutaneous
      tumours and in cutaneous lesions of infectious origin. They seem to play a
      crucial role in the initiation of the pathological processes of autoimmune
      diseases such as lupus or psoriasis. Their function within a tumour context is
      not as well known and is controversial. They could have a tolerogenic role
      towards tumour cells in the absence of an activator but they also have the
      capacity to become activated in response to Toll-like receptor (TLR) ligands and
      could therefore be useful for therapeutic purposes.

PMID- 19850551
TI  - Legislating tolerance: Spain's national public smoking law.
AB  - While Spain's national tobacco control legislation prohibits smoking in many
      indoor public places, the law provides for an exception to the prohibition of
      smoking by allowing separate seating sections and ventilation options in certain
      public places such as bars and restaurants, hotels and airports. Accordingly,
      Spain's law is not aligned with Article 8 Guidelines of the World Health
      Organization's Framework Convention on Tobacco Control, which requires parties to
      ensure universal protection against secondhand smoke exposure in all enclosed
      public places, workplaces and on all means of public transport. Spain's law is
      currently being promoted by the tobacco companies in other countries as a model
      for smoke-free legislation. In order to prevent weakening of smoke-free laws in
      other countries through industry-supported exceptions, we investigated the
      tactics used by the tobacco companies before the implementation of the new law
      and assessed the consequences of these actions in the hospitality sector.
      Internal tobacco industry documents made public through US litigation settlements
      dating back to the 1980s were searched in 2008-9. Documents show that tobacco
      companies sought to protect hospitality venues from smoking restrictions by
      promoting separate seating for smokers and ineffective ventilation technologies,
      supporting an unenforceable voluntary agreement between the Madrid local
      government and the hospitality industry, influencing ventilation standards
      setting and manipulating Spanish media. The Spanish National Assembly should
      adopt comprehensive smoke-free legislation that does not accommodate the
      interests of the tobacco industry. In doing so, Spain's smoke-free public places
      law would be better aligned with the Framework Convention on Tobacco Control.

PMID- 19850552
TI  - Recent tobacco tax rate adjustment and its potential impact on tobacco control in
      China.
AB  - OBJECTIVES: To compare the new tobacco tax structure effective from May 2009 with
      the tax structure before May 2009 and to analyse its potential impact. METHODS:
      Published government statistics and estimated price elasticities of the demand
      for cigarettes are used to estimate the impact of the new tax rate adjustment on
      cigarette consumption and population health. RESULTS: The new adjustment
      increased the tax rate by 11.7% points at the producer price level. Converting
      this 11.7% point increase to the retail price level would mean an increase of
      3.4% points in the retail price tax rate. Thus, China's new cigarette tax rate at
      the retail level would be 43.4% instead of the previous 40%. CONCLUSIONS: The
      primary motivation for the recent Chinese government tobacco tax adjustment is to
      raise additional government revenue. Because the additional ad valorem tax has
      not yet been transferred to smokers, there is no public health benefit. It is
      hoped that the Chinese government will pass along these taxes to the retail price
      level, which would result in between 640,000 and two million smokers quitting
      smoking and between 210,000 and 700,000 quitters avoiding smoking-related
      premature death.

PMID- 19850553
TI  - Secondhand smoke exposure (PM2.5) in outdoor dining areas and its correlates.
AB  - BACKGROUND: This study assessed the magnitude of secondhand smoke (SHS) exposure
      when people smoke in outdoor dining areas and explored conditions influencing
      exposure levels. METHODS: Data were gathered from 69 outdoor dining areas in
      Melbourne, Australia, during April/May 2007. Sitting at tables within 1 metre of
      an active smoker, the authors measured the concentration of particulate pollution
      (PM(2.5)) using TSI SidePak Personal Aerosol Monitors. PM(2.5) data were recorded
      by the monitor at 30-second intervals, and data were collected over an average of
      25.8 minutes per venue. Information was collected about the presence of overhead
      coverings and the number of patrons and lit cigarettes. RESULTS: The average
      background level of PM(2.5) was 8.4 microg/m(3) (geometric mean (GM)=6.1
      microg/m(3)), increasing to an average of 17.6 microg/m(3) (GM=12.7 microg/m(3))
      over the observational period and 27.3 microg/m(3) (GM=17.6 microg/m(3)) during
      the time that cigarettes were actively smoked near the monitor. There was
      substantial variation in exposure levels, with a maximum peak concentration of
      483.9 microg/m(3) when there were lit cigarettes close to the monitor. Average
      exposure levels increased by around 30% for every additional active smoker within
      1 metre of the monitor. Being situated under an overhead cover increased average
      exposure by around 50%. CONCLUSIONS: When individuals sit in outdoor dining
      venues where smokers are present it is possible that they will be exposed to
      substantial SHS levels. Significant increases in exposure were observed when
      monitors were located under overhead covers, and as the number of nearby smokers
      increased. The role of outdoor smoking restrictions in minimising exposure to SHS
      must be considered.

PMID- 19850554
TI  - Resting heart rate and excessive heart rate increase during pre-exercise mental
      stress: which one predicts mortality?

PMID- 19850556
TI  - Anomalous connection of the inferior vena cava to the left atrium diagnosed using
      three-dimensional echocardiography.

PMID- 19850558
TI  - Mitral valve re-repair: correlating real-time three-dimensional intra-operative
      transoesophageal echocardiography and surgical findings.

PMID- 19850557
TI  - Aortic remodelling in Fabry disease.
AB  - AIMS: To evaluate thoracic aortic dilation in patients with Fabry disease (FD).
      METHODS AND RESULTS: A cohort of 106 patients with FD (52 males; 54 females) from
      three European centres were studied. The diameter of the thoracic aorta was
      assessed at three levels (sinus of Valsalva, ascending aorta, and descending
      aorta) using echocardiograms and cardiovascular magnetic resonance imaging.
      Aortic dilation at the sinus of Valsalva was found in 32.7% of males and 5.6% of
      females; aneurysms were present in 9.6% of males and 1.9% of females. No aortic
      dilation was observed in the descending aorta. There was no correlation between
      aortic diameter at the sinus of Valsalva and cardiovascular risk factors.
      CONCLUSION: Fabry disease should be considered as a cardiovascular disease that
      affects the heart and arterial vasculature, including the thoracic aorta. Thus,
      patients with FD should be closely monitored for the presence, and possible
      progression and complications of aortic dilation. CLINICAL TRIAL REGISTRATION:
      Protocol 101/01. Ethics committee, Faculty of Medicine, Lausanne.

PMID- 19850559
TI  - Pregnancy-associated plasma protein-A is an independent short-time predictor of
      mortality in patients on maintenance haemodialysis.
AB  - AIMS: Mortality of maintenance haemodialysis (HD) patients is very high due to
      polymorbidity, mostly from metabolic and cardiovascular disease. In order to
      identify patients with high risk for life-threatening complications, reliable
      prognostic markers would be helpful. Pregnancy-associated plasma protein-A (PAPP
      A) has been shown to predict cardiovascular events and death in patients with
      stable coronary artery disease as well as in acute coronary syndrome in patients
      with normal renal function. It was the aim of this study to evaluate PAPP-A as a
      marker for death in patients on maintenance HD. METHODS AND RESULTS: PAPP-A serum
      levels were measured in 170 patients participating in the monitor! trial, a
      prospective dynamic dialysis cohort multicenter study in Switzerland. Patients
      were followed up for a median time of 17 months after measuring PAPP-A, and
      evaluated for death of any cause. Survivors and non-survivors were compared with
      regard to baseline PAPP-A concentrations. A multivariate logistic regression
      analysis for death was performed including PAPP-A, age, sex, number of
      comorbidities, dialysis vintage, Kt/V, IL-6, C-reactive protein, parathyroid
      hormone (PTH), Ca x PO(4) product, and total serum cholesterol. A cut-off value
      for PAPP-A was calculated for discrimination between patients with low and high
      mortality risk, respectively. A total of 23 deaths occurred during follow-up,
      equalling an incidence rate of 0.1. Baseline median PAPP-A levels were 40% higher
      in non-survivors vs. survivors (P = 0.023). In a multivariate analysis, only PAPP
      A, age, and Ca x PO(4) product were independent predictors of mortality. A cut
      off value of 24 mIU/L discriminates significantly (P = 0.015) between patients at
      low or high risk for death with a negative predictive value of 91%. CONCLUSION:
      PAPP-A is a novel and independent short-time predictor of mortality in a
      maintenance HD population. The pathogenetic relevance of PAPP-A, particularly in
      the development of cardiovascular disease, remains to be further elucidated.

PMID- 19850560
TI  - Hyponatremia in heart failure.
AB  - Hyponatremia is one of the newer and emerging risk factors for an adverse
      prognosis in chronic heart failure. Why decreased serum sodium is associated with
      worse prognosis remains unclear. It may reflect worsening heart failure and the
      deleterious effects of activation of neurohormones. The mechanism of hyponatremia
      in heart failure also remains unclear. A relatively greater degree of free-water
      retention compared to sodium retention is probably the major mechanism. The
      treatment of significant hyponatremia in heart failure is difficult. The
      conventional treatments such as fluid restriction, infusion of hypertonic saline,
      and aggressive diuretic therapies are not usually effective. Vasopressin receptor
      antagonists have been shown to enhance aquaresis and correct hyponatremia.
      However, long-term beneficial effects of such treatments in chronic heart failure
      have not been documented.

PMID- 19850561
TI  - Circulatory arrest in a brain-dead organ donor: is the use of cardiac compression
      permissible?
AB  - Care of the brain-dead patient is common in intensive care practice. Aggressive
      donor management is advocated to increase supply of viable organs. Significant
      controversy exists over cardiac resuscitation in patients determined dead by
      cardiac criteria. The issue, till now, has not been addressed in brain dead
      patients. We discuss a case of cardiac resuscitation of a brain-dead donor to
      ensure organ donation. This case allows us to examine the use of brain death
      criteria to declare death, the controversy regarding cardiac resuscitation in
      organ donor patients, and the standards for use of cardiac resuscitation in the
      organ donor declared dead by brain death criteria. The consent process for organ
      donation in brain dead patients should address the possibility of subsequent
      cardiac arrest.

PMID- 19850562
TI  - Utilization of blood spot testing for metabolic-genetic disorders in Honduras: is
      it time for newborn screening?
AB  - Honduran infant mortality (20/1000) has fallen below the Latin American newborn
      screening target rate (<30/1000). The authors report 2 Honduran maple syrup urine
      disease cases and a newborn screening pilot study. The first infant, diagnosed by
      plasma/urine testing in the U.S., prompted this study. Although marked
      clinical/radiological improvement occurred after treatment, moderate
      neurodevelopmental delays persist at 5 years. This 1-month, prospective study
      used blood spot specimens from hospitalized term Honduran neonates shipped
      overnight to South Carolina for routine newborn screening with electronic result
      submission to Honduras for follow-up. Of 88 consecutive neonates (mean age: 4.2
      days, standard deviation: 4.2 days) tested, 24 (0.6%) of 3837 completed tests
      were positive. Another infant with maple syrup urine disease, diagnosed after
      study completion by blood spot testing, later died. The study findings indicate
      that collaborative blood spot testing aids in the diagnosis of Honduran metabolic
      genetic disease. Newborn screening is now needed to diagnose and treat these
      diseases before morbidity/mortality develops.

PMID- 19850563
TI  - Recovery from spatial neglect and hemiplegia in a child despite a large anterior
      circulation stroke and Wallerian degeneration.
AB  - Prognosis after stroke in children is difficult given the paucity of literature
      regarding motor and cognitive recovery. Spatial neglect has been described in
      children after stroke, yet little evidence exists to guide clinicians and parents
      regarding its resolution. Wallerian degeneration on magnetic resonance imaging
      (MRI) suggests poor recovery in neonates and adults. We report near complete
      resolution of spatial neglect in 4 weeks and significant improvement in
      hemiplegia in a 9-year-old boy with a right anterior cerebral artery and middle
      cerebral artery infarction, despite Wallerian degeneration apparent on diffusion
      weighted imaging. Serial assessment of neglect documenting the rapid course of
      recovery is the unique feature of this case and may help serve as a guide to
      pediatricians and neurologists in assessment of young patients and counseling of
      parents. The lack of published outcome data suggests a need for larger studies
      about the recovery of spatial neglect and other cognitive symptoms following
      pediatric stroke.

PMID- 19850564
TI  - Successful treatment of acute coronary sinus thrombosis utilizing a Judkins right
      catheter in a patient receiving cardiac resynchronization therapy.

PMID- 19850565
TI  - In vitro activity of the new quinolone derivative RD-3 against clinical isolates
      of Mycoplasma pneumoniae and Mycoplasma hominis.

PMID- 19850566
TI  - Detection of methicillin-resistant Staphylococcus aureus ST398 in food samples of
      animal origin in Spain.

PMID- 19850567
TI  - Our approach to a renal transplant biopsy.
AB  - Kidney transplantation has become increasingly common in major health centres,
      making renal allograft evaluation through biopsy a common procedure. Early
      allograft dysfunction occurs in 30-50% of all transplants, while chronic graft
      failure is almost uniform at a rate of 2-4% a year. Allograft biopsy remains the
      gold standard for the diagnosis of graft dysfunction. Rejection, albeit the most
      important, is only one of many causes of allograft dysfunction. The widely
      accepted Banff classification has set criteria for the diagnosis of acute and
      chronic rejection. The major differential diagnoses are acute ischaemic injury,
      calcineurin inhibitor toxicity (acute and chronic), infections, including
      pyelonephritis and polyomavirus nephropathy, chronic obstruction/reflux,
      hypertension, and recurrent and de novo disease. In this review, there is an
      outline of the Banff criteria and their implications, the various causes of graft
      dysfunction, and a discussion on morphological guidelines towards the various
      diagnoses.

PMID- 19850568
TI  - Cyclists' attitudes toward policies encouraging bicycle travel: findings from the
      Taupo Bicycle Study in New Zealand.
AB  - Utility cycling provides substantial health, environmental and economic benefits.
      Despite a favourable trend in leisure-time cycling, cycling is infrequently used
      for everyday travel needs in New Zealand. This study investigated cyclists'
      attitudes toward environmental and policy measures that would encourage them to
      cycle more, particularly for a trip to work. A cross-sectional analysis was
      undertaken using baseline data obtained from the Taupo Bicycle Study, a web-based
      longitudinal study. The study population comprised 2469 cyclists, aged 16 years
      or over, who had enrolled in the 2006 Wattyl Lake Taupo Cycle Challenge. The
      majority (88%) reported the provision of bicycle lanes as an important factor
      that would encourage them to cycle more often, followed by bicycle paths (76%),
      better bicycle security (64%), reduced motor vehicle speed (55%) and bike
      friendly public transport (38%). Of those who reported travelling to work at
      least once a week (N = 2223), varying proportions reported shower facilities at
      work (61%), fewer difficult intersections (43%), rising fuel costs (41%), fewer
      car parks (27%), bike designed to commute (26%) and rising cost of car parking
      (25%) as important factors that would encourage them to cycle to work more often.
      There were important differences in these perceived influences defined by the
      participants' socio-demographic characteristics and current cycling habits.

PMID- 19850569
TI  - Ways of healthy aging: a case study of elderly people in a Northern Thai village.
AB  - This ethnographic study was conducted to explore ways of healthy aging and the
      influence of culture on health-related behaviors in a rural community in Northern
      Thailand. In-depth interviews, focus group discussions, participant observations
      and field notes were used to understand the lives of seven healthy Thai older
      adults aged 75 years and over. Data were collected from March 2007 to February
      2008, with ongoing ethnographic analysis involving coding, identifying patterns,
      generalizing and making reflective notes to elucidate the cultural patterns of
      behavior. All informants perceived health as interrelated with their life styles,
      which was, in turn, closely related to their cultural roots, suggesting that
      culture influences the health of all members of smaller, closely knit
      communities, including the elderly, by integrating physical, social and spiritual
      health for older adults and their families.

PMID- 19850570
TI  - Does a population-based multifactorial lifestyle intervention increase social
      inequality in physical activity? The Inter99 study.
AB  - AIM: To examine the effect of a multifactorial lifestyle intervention on 5-year
      change in physical activity (PA) and to explore whether length of education had
      an impact on the effect of the intervention. METHODS: Two random samples (high
      intervention group A, n=11 708; low intervention group B, n=1308) were invited
      for a health examination, assessment of absolute risk of ischemic heart disease
      and individual lifestyle counselling. The participation rate was 52.5%. High-risk
      individuals in group A were also offered group-based counselling on diet and PA
      and/or smoking cessation. High-risk individuals in group B were referred to usual
      care. All high-risk individuals were reinvited for examination and counselling
      after 1 and 3 years, and all participants were reexamined after 5 years. The
      control group (group C, n=5264, response rate 61.1%) answered a mailed
      questionnaire. Change in self-reported PA from baseline to 5-year follow-up was
      the main outcome. Level of education was classified as no vocational training,
      <=4 years and >4 years. Data were analysed using longitudinal linear regression
      models with random intercepts. RESULTS: In men, the high-intensity intervention
      had a beneficial effect on PA level after 5 years. The age- or time-related
      decrease in PA was approximately 30 min/week less compared to men in the control
      group (p<0.0001). Level of education had no significant impact on the effect of
      the intervention neither in men (p=0.39) nor in women (p=0.32). CONCLUSION: A
      population-based multifactorial lifestyle intervention did not influence social
      inequality in PA.

PMID- 19850571
TI  - Medication use by athletes during the Athens 2004 Paralympic Games.
AB  - OBJECTIVE: To examine the use of food supplements and pharmaceutical preparations
      by elite Paralympic athletes. DESIGN: Survey study. SETTING: Athens 2004
      Paralympic Games. PARTICIPANTS: Data obtained from two sources: (i) athletes'
      declaration of intake of drugs/supplements recorded on the Doping Control
      Official Record during sample collection for doping control; (ii) athletes'
      application forms for granting of a therapeutic use exemption. MAIN OUTCOME
      MEASURES: Classification of declared food supplements according to the active
      ingredient and medications according to therapeutic actions and active compounds.
      RESULTS: 64.2% of the athletes tested for doping control declared use of
      medications or food supplements, and 81.3% of these athletes declared intake of
      fewer than four preparations. Non-invasive routes of administration dominated.
      Food supplements (42.1%) were popular, and drugs used to treat several
      pathological conditions noted. Non-steroidal anti-inflammatory agents and
      analgesics were commonly used (9.8% and 5.6%, respectively). The prevalence of
      inhaled beta2-agonist use (4.8%) was higher than expected and exceeded that at
      the Athens Olympic Games. CONCLUSIONS: This review, the first to examine elite
      Paralympic athletes, shows a more rational approach to the use of medication and
      food supplements, but a similar consumption pattern to that of athletes at the
      Athens Olympic Games. Because of the dearth of such studies, consumption trends
      among Paralympic athletes remain unclear. The need to counsel athletes with
      disabilities on their nutritional needs is confirmed, and close monitoring by
      healthcare professionals is recommended.

PMID- 19850573
TI  - Relative importance of pacing strategy and mean power output in 1500-m self-paced
      cycling.
AB  - INTRODUCTION: Both mean power output (MPO) and the distribution of the available
      energy over the race, that is, pacing strategy, are critical factors in
      performance. The purpose of this study was to determine the relative importance
      of both pacing strategy and MPO to performance. METHODS: Six well-trained,
      regionally competitive cyclists performed four 1500-m ergometer time trials (~2
      min). For each subject, the fastest (Fast) and slowest (Slow) time trials were
      compared and the relative importance of differences in power output and pacing
      strategy were determined with an energy flow model. RESULTS: The difference in
      final time between Fast and Slow was 4.0 (2.5) s. Fast was performed with a
      higher MPO (437.8 (32.3) W vs 411.3 (39.0) W), a higher aerobic peak power (295.3
      (36.8) vs 287.5 (34.7) W) and a higher anaerobic peak power (828.8 (145.4) W vs
      649.5 (112.2) W) combined with a relatively higher, but not statistically
      different anaerobic rate constant (0.051 (0.016) vs 0.041 (0.009) W). The changes
      in MPO (63% anaerobic, 37% aerobic) largely explained the differences in final
      times. Athletes chose a different pacing strategy that was close to optimal for
      their physiological condition in both Fast and Slow. CONCLUSION: Differences in
      intraindividual performance were mainly caused by differences in MPO. Athletes
      seemed to be able to effectively adjust their pacing profile based on their
      "status of the day". Keywords modelling performance, energy expenditure, aerobic,
      anaerobic, sports.

PMID- 19850572
TI  - Decreased incidence of knee posterior cruciate ligament injury in Australian
      Football League after ruck rule change.
AB  - OBJECTIVE: To assess whether a rule change introduced in the Australian Football
      League (AFL) before the start of the 2005 season, to limit the run-up of ruckmen
      at the centre bounce, has been successful in reducing the incidence of knee
      posterior cruciate ligament (PCL) injuries. DESIGN: Cohort study with historical
      control. SETTING: The AFL competition from 1992 to 2008 inclusive. ASSESSMENT OF
      RISK FACTORS: The presence of a rule change (four seasons) compared with the
      previous 13 seasons (divided into two eras of seven and six seasons). MAIN
      OUTCOME MEASURE: Occurrence of knee PCL injury during a regular season or finals
      match, both from all causes and specifically from centre bounce ruck collision
      mechanisms. RESULTS: From 1992 to 1998 there were 11.0 PCL injuries per 10,000
      player-hours, with 0.8 ruck injuries per 10,000 centre bounces. From 1999 to
      2004, the rates increased to 12.9 per 10,000 player-hours and 5.6 ruck injuries
      per 10,000 centre bounces (p<0.01). The rates reduced to 5.9 PCL injuries per
      10,000 player-hours and 0.9 ruck injuries per 10,000 centre bounces in the period
      2005-2008 following the rule change (p<0.01). There was a lower relative risk in
      2005-2008 than in 1999-2004 of incurring a centre bounce ruck PCL injury (0.16
      (95% CI 0.04 to 0.69)) or of sustaining any PCL injury (0.45 (95% CI 0.28 to
      0.75)). CONCLUSION: A rule change in the AFL to limit the run-up of ruckmen at
      the centre bounce has successfully reduced the rate of PCL injuries with this
      mechanism, with the total incidence of PCL injuries also falling.

PMID- 19850574
TI  - Optimal pacing strategy: from theoretical modelling to reality in 1500-m speed
      skating.
AB  - PURPOSE: Athletes are trained to choose the pace which is perceived to be correct
      during a specific effort, such as the 1500-m speed skating competition. The
      purpose of the present study was to "override" self-paced (SP) performance by
      instructing athletes to execute a theoretically optimal pacing profile. METHODS:
      Seven national-level speed-skaters performed a SP 1500-m which was analysed by
      obtaining velocity (every 100 m) and body position (every 200 m) with video to
      calculate total mechanical power output. Together with gross efficiency and
      aerobic kinetics, obtained in separate trials, data were used to calculate
      aerobic and anaerobic power output profiles. An energy flow model was applied to
      SP, simulating a range of pacing strategies, and a theoretically optimal pacing
      profile was imposed in a second race (IM). RESULTS: Final time for IM was ~2 s
      slower than SP. Total power distribution per lap differed, with a higher power
      over the first 300 m for IM (637.0 (49.4) vs 612.5 (50.0) W). Anaerobic
      parameters did not differ. The faster first lap resulted in a higher aerodynamic
      drag coefficient and perhaps a less effective push-off. CONCLUSION: Experienced
      athletes have a well-developed performance template, and changing pacing strategy
      towards a theoretically optimal fast start protocol had negative consequences on
      speed-skating technique and did not result in better performance.

PMID- 19850575
TI  - International Paralympic Committee position stand--background and scientific
      principles of classification in Paralympic sport.
AB  - The Classification Code of the International Paralympic Committee (IPC), inter
      alia, mandates the development of evidence-based systems of classification. This
      paper provides a scientific background for classification in Paralympic sport,
      defines evidence-based classification and provides guidelines for how evidence
      based classification may be achieved. Classification is a process in which a
      single group of entities (or units) are ordered into a number of smaller groups
      (or classes) based on observable properties that they have in common, and
      taxonomy is the science of how to classify. Paralympic classification is
      interrelated with systems of classification used in two fields: Health and
      functioning. The International Classification of Functioning, Disability and
      Health is the most widely used classification in the field of functioning and
      health. To enhance communication, Paralympic systems of classification should use
      language and concepts that are consistent with the International Classification
      of Functioning, Disability and Health. Sport. Classification in sport reduces the
      likelihood of one-sided competition and in this way promotes participation. Two
      types of classification are used in sport-performance classification and
      selective classification. Paralympic sports require selective classification
      systems so that athletes who enhance their competitive performance through
      effective training will not be moved to a class with athletes who have less
      activity limitation, as they would in a performance classification system.
      Classification has a significant impact on which athletes are successful in
      Paralympic sport, but unfortunately issues relating to the weighting and
      aggregation of measures used in classification pose significant threats to the
      validity of current systems of classification. To improve the validity of
      Paralympic classification, the IPC Classification Code mandates the development
      of evidence-based systems of classification, an evidence-based system being one
      in which the purpose of the system is stated unambiguously; and empirical
      evidence indicates the methods used for assigning class will achieve the stated
      purpose. To date, one of the most significant barriers to the development of
      evidence-based systems of classification has been absence of an unambiguous
      statement of purpose. To remedy this, all Paralympic systems of classification
      should indicate that the purpose of the system is to promote participation in
      sport by people with disabilities by minimising the impact of eligible impairment
      types on the outcome of competition. Conceptually, in order to minimise the
      impact of impairment on the outcome of competition, each classification system
      should: describe eligibility criteria in terms of: type of impairment and
      severity of impairment; describe methods for classifying eligible impairments
      according to the extent of activity limitation they cause. To classify
      impairments according to the extent of activity limitation they cause requires
      research that develops objective, reliable measures of both impairment and
      activity limitation and investigates the relative strength of association between
      these constructs in a large, racially representative sample. The paper outlines a
      number of objective principles that should considered when deciding how many
      classes a given sport should have: the number of classes in a sport should not be
      driven by the number of athletes in a sport at a single time point.

PMID- 19850576
TI  - Eccentric hip adduction and abduction strength in elite soccer players and
      matched controls: a cross-sectional study.
AB  - BACKGROUND: Eccentric hip adduction and abduction strength plays an important
      role in the treatment and prevention of groin injuries in soccer players. Lower
      extremity strength deficits of less than 10% on the injured side, compared to the
      uninjured side, have been suggested as the clinical milestone before returning to
      sports following injury. OBJECTIVE: To examine whether a side-to-side eccentric
      hip adduction or abduction strength symmetry can be assumed in non-injured soccer
      players and matched controls. MATERIAL AND METHODS: Nine elite soccer players
      19.4 (1.5) years and nine recreational athletes 19.5 (2.0) years matched for sex,
      height and weight were included. Eccentric hip adduction and abduction strength
      of the dominant and non-dominant leg was tested for all the participants using an
      eccentric break test with a handheld dynamometer. RESULTS: The dominant leg was
      14% stronger than the non-dominant leg for hip adduction in the soccer players
      (p<0.05). No other side-to-side strength differences existed in soccer players or
      controls. In soccer players, hip abduction strength was 17-31% greater than
      controls for the dominant (p<0.05) and non-dominant leg (p<0.001). CONCLUSION:
      Eccentric hip adduction strength was greater in the dominant leg than in the non
      dominant leg in soccer players, but not in matched controls. Eccentric hip
      abduction strength was greater in soccer players than matched controls, but
      soccer does not seem to induce a similar eccentric strength adaptation in the hip
      adductors.

PMID- 19850577
TI  - Early profiles of clinical evolution after intravenous thrombolysis in an
      unselected stroke population.
AB  - BACKGROUND: Intravenous recombinant tissular plasminogen activator (rt-PA) is the
      only approved pharmacological treatment for acute ischaemic stroke. The authors
      aimed to analyse potential causes of the variable effect on early course and late
      outcome. METHODS AND RESULTS: 136 patients (42% women, 58% men) treated with
      intravenous rt-PA within 3 h of stroke onset in an acute stroke unit over a 3
      year period, were included. Early clinical profiles of evolution at 48 h were
      divided into clinical improvement (CI) (decrease >4 points in the National
      Institute of Health Stroke Scale (NIHSS)); clinical worsening (CW) (increase >4
      points NIHSS); clinical worsening after initial improvement (CWFI) (variations of
      >4 points in the NIHSS). Patients with clinical stability (no NIHSS modification
      or <4 points) were excluded. The patients showed in 66.9% CI, 13.2% CW 8.1 % CWFI
      and 11.8% remained stable. Female sex, no hyperlipaemia and peripheral arterial
      disease were associated with CW. Male sex and smoking were associated with CI.
      Absence of arterial occlusion on admission (28.4%) and arterial recanalisation at
      24 h were associated with CI. Main causes of clinical deterioration included
      symptomatic intracranial haemorrhage (sICH), persistent occlusion and cerebral
      oedema. 23.5% developed ICH, 6.6% of which had sICH. At 3 months, 15.5% had died.
      Mortality was increased in CW, mainly related to sICH and cerebral oedema. The
      outcome of CWFI was intermediate between CW and CI. CONCLUSIONS: Early clinical
      profiles of evolution in thrombolysed patients vary considerably. Even with CI,
      it is critical to maintain vessel permeability to avoid subsequent CW.

PMID- 19850578
TI  - A brain PET study in patients with narcolepsy-cataplexy.
AB  - OBJECTIVE: To investigate brain changes in both basal and cataplectic conditions
      in awake patients with narcolepsy-cataplexy. BACKGROUND: Recent insights in
      pathophysiology have demonstrated that narcolepsy-cataplexy is caused by early
      loss of hypothalamus hypocretin neurons. However, the neurophysiological
      mechanisms underlying sleepiness and the dramatic cataplexy reaction to positive
      emotion remain unclear. METHODS: Twenty-one patients with narcolepsy-cataplexy
      and 21 age- and sex-matched controls were included. Diagnosis of narcolepsy was
      fully confirmed by polysomnography, HLA DQB1*0602 and CSF hypocretin levels
      (n=9). Seven patients were free of all drugs, and 14 were treated with
      psychostimulant and/or anticataplectic drugs. (18)-F-fluorodeoxy glucose positron
      emission tomography procedures were performed at baseline in all subjects and
      during cataplexy attacks (n=2). RESULTS: The authors found significant
      hypermetabolism in narcolepsy-cataplexy in fully awake condition in the limbic
      cortex specifically in the anterior and mid cingulate cortex, in the right cuneus
      and lingual gyrus. In contrast, no hypometabolism was found. Hypermetabolism was
      detected in the cerebellum and pre-postcentral gyri in treated compared with
      untreated patients. During cataplectic attacks, cerebral metabolism significantly
      increased in the bilateral pre-postcentral gyri, primary somatosensory cortex,
      with a marked decrease in the hypothalamus. CONCLUSION: Hypermetabolism was found
      in the executive network in narcolepsy at baseline in fully awake condition. Wake
      state assessment during scanning appears critical to avoid results showing
      altered functional neurocircuitry secondary to sleepiness and not to the
      underlying neurological disorder per se. Finally, cataplexy attacks were
      characterised by a hypometabolism in the hypothalamus associated with wide
      bilateral brain area hypermetabolisms.

PMID- 19850579
TI  - Atrogin-1 and MuRF1 regulate cardiac MyBP-C levels via different mechanisms.
AB  - AIMS: Familial hypertrophic cardiomyopathy (FHC) is frequently caused by cardiac
      myosin-binding protein C (cMyBP-C) gene mutations, which should result in C
      terminal truncated mutants. However, truncated mutants were not detected in
      myocardial tissue of FHC patients and were rapidly degraded by the ubiquitin
      proteasome system (UPS) after gene transfer in cardiac myocytes. Since the
      diversity and specificity of UPS regulation lie in E3 ubiquitin ligases, we
      investigated whether the muscle-specific E3 ligases atrogin-1 or muscle ring
      finger protein-1 (MuRF1) mediate degradation of truncated cMyBP-C. METHODS AND
      RESULTS: Human wild-type (WT) and truncated (M7t, resulting from a human
      mutation) cMyBP-C species were co-immunoprecipitated with atrogin-1 after
      adenoviral overexpression in cardiac myocytes, and WT-cMyBP-C was identified as
      an interaction partner of MuRF1 by yeast two-hybrid screens. Overexpression of
      atrogin-1 in cardiac myocytes decreased the protein level of M7t-cMyBP-C by 80%
      and left WT-cMyBP-C level unaffected. This was rescued by proteasome inhibition.
      In contrast, overexpression of MuRF1 in cardiac myocytes not only reduced the
      protein level of WT- and M7t-cMyBP-C by >60%, but also the level of myosin heavy
      chains (MHCs) by >40%, which were not rescued by proteasome inhibition. Both
      exogenous cMyBP-C and endogenous MHC mRNA levels were markedly reduced by MuRF1
      overexpression. Similar to cardiac myocytes, MuRF1-overexpressing (TG) mice
      exhibited 40% lower levels of MHC mRNAs and proteins. Protein levels of cMyBP-C
      were 29% higher in MuRF1 knockout and 34% lower in TG than in WT, without a
      corresponding change in mRNA levels. CONCLUSION: These data suggest that atrogin
      1 specifically targets truncated M7t-cMyBP-C, but not WT-cMyBP-C, for proteasomal
      degradation and that MuRF1 indirectly reduces cMyBP-C levels by regulating the
      transcription of MHC.

PMID- 19850580
TI  - Descemet membrane endothelial keratoplasty with a stromal rim (DMEK-S).
AB  - AIM: To describe a novel technique for the preparation and transplantation of
      posterior corneal lamellae consisting of endothelium and bare Descemet membrane
      with a stromal supporting rim. METHODS: Posterior lamellar discs for Descemet
      membrane endothelial keratoplasty with a stromal rim (DMEK-S) were prepared
      manually immediately before surgery using the big bubble technique. The
      retrospective case series that underwent DMEK-S comprised 20 eyes of 18 patients
      with endothelial dysfunction. Best-corrected visual acuity (BCVA) and endothelial
      cell density (ECD) were measured preoperatively and 12-24 months after DMEK-S.
      RESULTS: At the end of the follow-up, 10 out of 18 eyes achieved a BCVA of 1.0 or
      better, and 17 reached 0.5 or better. Primary graft failure occurred in two eyes.
      The average ECD at 1 year was 1608 (+/-503) cells/mm(2), that is, a mean cell
      loss from preoperative values of 44%. Partial early postoperative graft
      detachment (12 of 20 eyes) was treated by injecting an air bubble into the
      anterior chamber in all cases. The loss of donor corneas during preparation
      decreased from approximately 10 to 5% as more experience was acquired with the
      procedure. CONCLUSIONS: Preliminary outcomes show that DMEK-S may be used in the
      treatment of corneal endothelial dysfunction. As this approach is entirely
      manual, and no special surgical equipment is needed, it has the potential to
      become widely adopted.

PMID- 19850581
TI  - Prevalence of heterophoria and associations with refractive error, heterotropia
      and ethnicity in Australian school children.
AB  - AIMS To establish the prevalence of heterophoria and its association with
      refractive error and ethnicity in a population-based study of Australian
      schoolchildren. METHODS The Sydney Myopia Study is a stratified, random cluster
      (school-based) sample of 4093 students (examined: 2003-2005). Two samples aged 6
      (n=1692) and 12 years (n=2289) without heterotropia were included. Prevalent
      heterophoria was assessed using cover un-cover and prism bar alternate cover
      testing at 33 cm and 6 m distance fixation. Cycloplegic autorefraction (1%
      cyclopentolate) was performed. Significant refractive error was defined as < or =
      0.50SE and > or =+2.00SE. RESULTS Exophoria was highly prevalent at near fixation
      (age 6: 58.3%, age 12: 52.2%). Orthophoria predominated at distance fixation (age
      6: 85.4%, age 12: 90.9%). Hyperopia was associated with esophoria at near (age 6:
      OR 1.7, 95% CI 1.1 to 2.8, age 12: OR 2.9, CI 1.1 to 2.8) and distance fixation
      (age 6: OR 9.7, CI 3.5 to 26, age 12: 9.6 OR, CI 4.2 to 22). Myopia was
      associated with exophoria at near (OR 2.1, CI 1.5 to 2.7) and distance fixation
      (OR 3.1, CI 2.1 to 4.4) for 12-year-old children only. Exophoria was more
      frequent in children of East Asian than European Caucasian origins, even after
      adjusting for refraction; at near (age 6: OR 1.4, CI 1.0 to 2.0, age 12: OR 1.4,
      CI 1.0 to 1.9) and distance (age 12: OR 1.7, CI 1.1 to 2.7). CONCLUSION Contrary
      to other studies, exophoria, not orthophoria, was predominant for near. Exophoria
      was more prevalent in children of East Asian origin. Longitudinal studies are
      needed to establish if incident heterotropia is preceded by heterophoria.

PMID- 19850582
TI  - Detection of Mycobacterium tuberculosis in corneas from donors with active
      tuberculosis disease through polymerase chain reaction and culture.
AB  - OBJECTIVE: To determine if Mycobacterium tuberculosis can be detected in corneas
      of donors who have active tuberculosis (TB) disease using polymerase chain
      reaction (PCR) or culture. DESIGN: This is a prospective cross-sectional study.
      PARTICIPANTS: 25 corneas (12 from TB-negative donors and 13 from TB-positive
      donors) from the Sta. Lucia International Eye Bank were submitted to the TB
      Research Laboratory, Medical Research Laboratory, Department of Medicine, UP-PGH,
      for diagnostic evaluation. INTERVENTION: Corneas were evaluated using PCR test
      for M tuberculosis. Acid-fast bacilli smear and culture were also done. MAIN
      OUTCOME MEASURES: Result of laboratory findings. RESULTS: Among 12 TB-negative
      donors, there were 2 (16.67%) corneas that were PCR negative for M tuberculosis,
      whereas 10 (83.33%) corneas were PCR positive for M tuberculosis. Among 13 TB
      positive donors, there were 7 (53.85%) corneas that were PCR negative for M
      tuberculosis, whereas 6 (46.15%) corneas were PCR positive for M tuberculosis.
      All cultures were negative. CONCLUSION: PCR for M tuberculosis was positive for
      some TB-positive donors as well as TB-negative donors. However, all cultures were
      negative. It is recommended that further studies be done to investigate if
      recipients with PCR-positive corneas will eventually lead to disease transmission
      or not. It is further recommended that such findings be used to re-evaluate
      criteria for suitability of donors with tuberculosis.

PMID- 19850583
TI  - Clinical evaluation of the MacuScope macular pigment densitometer.
AB  - BACKGROUND/AIMS: The MacuScope uses a psychophysical technique called
      heterochromic flicker photometry to measure macular pigment optical density
      (MPOD). Our aim was to determine the measurement variability (noise) of the
      MacuScope. METHODS: Thirty-eight normally sighted participants who ranged in age
      from 19 to 46 years (25.7+/-7.6 years) were recruited from staff and students of
      Aston University. Data were collected by two operators, HB and JA, in two
      sessions separated by 1 week in order to assess test repeatability and
      reproducibility. RESULTS: The overall mean MPOD for the cohort was 0.47+/-0.14.
      There was a significant negative correlation between MacuScope MPOD readings and
      age (r=-0.368, p=0.023). Coefficients were 0.45 and 0.58 for repeatability, and
      0.49 and 0.36 for reproducibility. For each pair of results, there was a
      significant positive correlation between mean and difference MPOD values.
      CONCLUSIONS: If MPOD is being monitored over time then any change less than 0.58
      units should not be considered clinically significant as it is very likely to be
      due to instrument noise. The size of the coefficient appears to be positively
      correlated with MPOD.

PMID- 19850584
TI  - Psychosocial impact of visual impairment in working-age adults.
AB  - AIM: To review the evidence for the presence of lower levels of psychosocial well
      being in working-age adults with visual impairment and for interventions to
      improve such levels of psychosocial well-being. METHODS: Systematic review of
      quantitative studies published in English from 2001 to July 2008 that measured
      depression/mental health, anxiety, quality of life, social functioning or social
      support. RESULTS: Included were 29 studies that measured one or more outcomes (N
      = 52). Working-age adults with visual impairment were significantly more likely
      to report lower levels of mental health (mean difference = 14.51/100), social
      functioning (MD = 11.55/100) and quality of life. Studies regarding the
      prevalence of depressive symptoms produced inconsistent results but had
      methodological limitations. CONCLUSIONS: Future research is required into the
      prevalence of loneliness, anxiety and depression in adults with visual
      impairment, and to evaluate the effectiveness of interventions for improving
      psychosocial well-being such as counselling, peer support and employment
      programmes.

PMID- 19850585
TI  - Continuous, non-invasive measurement of the haemodynamic response to submaximal
      exercise in patients with diabetes mellitus: evidence of impaired cardiac reserve
      and peripheral vascular response.
AB  - BACKGROUND: Reduced exercise capacity in diabetics has been attributed to
      limitations in cardiac function and microvascular dysfunction leading to impaired
      oxygen supply and nutritive perfusion to exercising muscles. OBJECTIVE: To study
      changes in cardiac function and microvascular utilisation during exercise in
      diabetic individuals compared to age-matched controls. METHODS: Diabetics with
      glycosylated haemoglobin (HbA(1c)) < 8 (n = 31), diabetics with HbA(1c) > or = 8
      (n = 38) and age-matched non-diabetic controls (n = 32) performed exercise at 50
      W for 10 minutes followed by recovery, with continuous monitoring of cardiac
      function by impedance cardiography and regional flow and oxygen saturation by
      laser Doppler and white light spectroscopy. RESULTS: In the diabetics, cardiac
      reserve during exercise and cardiac overshoot during recovery are significantly
      reduced because of reduction in capacity to increase stroke volume. Regional flow
      to the exercising muscle is reduced and there is also disproportionately greater
      desaturation of the regional flow. Abnormalities in cardiac function and regional
      perfusion are related to the severity of diabetes. CONCLUSION: Cardiac response
      to exercise is attenuated significantly in diabetic individuals. Simultaneously,
      there is impairment in the regional distribution. These changes could be the
      harbinger of reduced exercise capacity in diabetics.

PMID- 19850586
TI  - European community and US-FDA approval of recombinant human antithrombin produced
      in genetically altered goats.
AB  - Thrombin and factor Xa play a central role in thrombogenesis in both medical and
      surgical patients. Antithrombin (AT) is the key inhibitor, which controls the
      action of these enzymes in hypercoagulable states. The AT concentrates prepared
      from human blood have been used to treat patients with thrombotic disorders and
      heparin resistance. The AT concentrates are prepared from pooled human plasma and
      beside limited supply, suffer from viral and other biological contaminants. The
      availability of recombinant human AT (rhAT) obtained from genetically engineered
      goats provide a biologically equivalent product that can be used in practically
      all indications where human AT is indicated including heparin resistance.
      Moreover, because of its high affinity to heparin and related drugs, recombinant
      AT can also be developed in further indications. On review of the preclinical and
      clinical data on the safety and efficacy, the European Union and U.S. Food and
      Drug Administration (US-FDA) have recently approved the use of rhAT in specified
      clinical indications.

PMID- 19850587
TI  - FXa inhibition and coagulation changes during DVT prophylaxis by enoxaparin over
      the course of a 15-day follow-up in septic patients.
AB  - The objective of our study was to examine the changes in coagulation parameters
      and inflammatory reaction over the course of 15 days in patients with severe
      sepsis. We tried to identify mechanisms by which sepsis-induced
      pathophysiological changes may influence the effectiveness of subcutaneously (SC)
      administered enoxaparin 40 mg once daily. A total of 16 patients (8 men, 8 women;
      age 35-83 years) meeting the inclusion criteria of severe sepsis were enrolled in
      this study. The follow-up was performed on days 1, 2, 3, 6, 9, 12, and 15 of
      hospitalization at the intensive care unit (ICU). Blood coagulation (activated
      partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen,
      antithrombin (AT), protein C [PC], D-dimer, fragment 1.2 [F1.2], factor Xa [FXa]
      inhibition) and inflammatory reactants (interleukin 6 [IL-6], C-reactive protein
      [CRP], orosomucoid, alpha-1-antitrypsin) were tested. The mean FXa inhibition was
      0.17 (+ or - 0.17) IU/mL. The arbitrarily established range of FXa inhibition for
      prophylaxis, 0.2 to 0.4 IU/mL, was reached in 22 cases (20%), while in 74 cases
      (68%), it was below and in 13 cases (12%) above the aforementioned range. Factor
      Xa inhibition positively correlated with AT (r = .42; P < .001) and PC (r = .45;
      P < .001) activities. A negative correlation was found between the FXa inhibition
      and alpha-1-antitrypsin concentrations (r = -.33; P = .01) but only in the
      subgroup with alpha-1-antitrypsin concentrations > or = 2.2 g/L. We confirmed
      that in most patients with sepsis, the prophylaxis with enoxaparin did not lead
      to the required FXa inhibition. The inhibition of FXa by enoxaparin depends
      mainly on the AT and PC activities.

PMID- 19850588
TI  - Mechanical methods for thrombosis prophylaxis.
AB  - Prevention of venous thromboembolism (VTE) remains the number one preventable
      cause of death in hospitalized patients. The pathogenesis of thrombosis involves
      the triad of venous stasis, dilatation of the leg veins, and changes in
      coagulability of the blood. These changes can be modified by the use of
      intermittent pneumatic compression devices (IPC) and, to a much lesser extent, by
      graduated compression hose (GCS). Studies have shown the effectiveness of GCS in
      preventing deep vein thrombosis (DVT) compared to placebo, but there is no
      evidence that they reduce the incidence of pulmonary emboli (PE). No venographic
      data are available regarding the efficacy of GCS; however, IPC have shown
      excellent efficacy in several venographic studies over the past 25 years.
      Mechanical methods are important to use in situations where the risk of bleeding
      exists, thereby making the use of anticoagulants hazardous. One of the key uses
      for mechanical methods is in combination with anticoagulants in patients at the
      highest risk of developing VTE. Chest consensus guidelines assigns a 2A
      recommendation for the use of combination prophylaxis in the highest risk
      patients. Unfortunately, studies to show which type of leg compression device is
      optimal for DVT prevention are not available, so individual preference, ease of
      use, and company support are the determining factors at the present time.
      Finally, compliance using these devices is a major problem, and until systems
      have been developed to easily monitor and ensure compliance, these methods will
      enjoy only limited use.

PMID- 19850589
TI  - Relative purity of different bovine thrombin preparations.
AB  - The aim of this study was to compare the relative purity of bovine crude thrombin
      and its purified forms, namely, thrombin 4A and thrombin 4B (the products of King
      Pharma, Middleton, Wisconsin) by virtue of the detection of bovine prothrombin
      related antigens in these preparations. Bovine prothrombin was administered
      intravenously to 3 individual rabbits on days 0, 21, 42, 91, 123, and 151 using
      standard immunologic method. Blood was drawn from each rabbit on days 30, 50,
      105, 137, and 165, and the pooled antisera from 3 rabbits were purified to
      isolate immunoglobulin G (IgG) using protein G affinity columns. Using Western
      blotting method, serially diluted bovine crude thrombin, thrombin 4A, and 4B
      preparations were probed using the prothrombin IgGs obtained from each time point
      to explore prothrombin-related antigens in these preparations. The results
      revealed that compared with the prothrombin IgG collected on day 30, the IgGs
      collected on days 50 to 165 showed a time-dependent increase in their ability to
      detect the prothrombin-related antigens in 3 bovine thrombin preparations
      studied. The lowest amount of crude thrombin, thrombin 4A, and 4B preparations
      that prothrombin IgG could detect was 0.125, 10, and 20 U, respectively. The rank
      order of the number of immunoreactive bands detectable in 3 bovine thrombin
      preparations probed by the prothrombin IgGs collected from any given time point
      was always the same: crude thrombin > thrombin 4A > thrombin 4B. The results
      indicate that thrombin 4B preparation contains the least amount of antigens
      detectable by prothrombin IgG, suggesting that relatively thrombin 4B represents
      the most purified thrombin preparation among the 3 thrombin preparations studied.

PMID- 19850590
TI  - Posttraumatic growth and social support in individuals with infertility.
AB  - BACKGROUND: While research on the psychological experiences of infertility has
      focused almost exclusively on the negative aspects, clinical experience with
      individuals and couples facing infertility has demonstrated that personal gain
      can also arise from the struggle involved. This study examined whether
      individuals who struggle with infertility report posttraumatic growth (PTG), and
      if perceived availability of and satisfaction with social support are associated
      with such growth. Other correlates of PTG are reported as well. METHODS: Using a
      cross-sectional design, a convenience sample of 121 individuals with infertility
      completed a background questionnaire, the Posttraumatic Growth Inventory and the
      Social Support Questionnaire. RESULTS: While individuals reported moderate PTG,
      moderate availability of, and high satisfaction with social support, there was no
      significant association between the variables. Infertility-related variables
      emerged as central to explaining PTG with those with non-female related diagnoses
      and unexplained diagnoses demonstrating lower PTG than others (t = 2.96, t = 3.6,
      respectively, P < or = 0.05). Additionally, live birth deliveries was positively
      associated with PTG (r(2) = 0.22, P < or = 0.02), and those who engaged in clergy
      counseling had higher PTG than those who did not (t = 2.34, P < or = 0.02).
      Determinants were unexplained infertility (lower PTG) and number of live birth
      deliveries (higher PTG). CONCLUSIONS: In spite of limitations related to the
      convenience sampling, correlational design and subjective self-report nature of
      the data, findings suggest that individuals who suffer from infertility can
      experience personal growth. Further research will help identify correlates and
      provide guidance for mental health practitioners on counseling infertility
      patients to promote growth.

PMID- 19850591
TI  - Increased risk of blastogenesis birth defects, arising in the first 4 weeks of
      pregnancy, after assisted reproductive technologies.
AB  - BACKGROUND: The reasons for increased birth defect prevalence following in-vitro
      fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are largely
      unknown. Classification of birth defects by pathology rather than organ system,
      and examination of the role of embryo freezing and thawing may provide clues to
      the mechanisms involved. This study aimed to investigate these two factors.
      METHOD: Data on 6946 IVF or ICSI singleton pregnancies were linked to perinatal
      outcomes obtained from population-based data sets on births and birth defects
      occurring between 1991 and 2004 in Victoria, Australia. These were compared with
      20,838 outcomes for singleton births in the same population, conceived without
      IVF or ICSI. Birth defects were classified according to pathogenesis. RESULTS:
      Overall, birth defects were increased after IVF or ICSI [adjusted odds ratio (OR)
      1.36; 95% CI: 1.19-1.55] relative to controls. There was no strong evidence of
      risk differences between IVF and ICSI or between fresh and thawed embryo
      transfer. However, a specific group, blastogenesis birth defects, were markedly
      increased [adjusted OR 2.80, 95% CI: 1.63-4.81], with the increase relative to
      the controls being significant for fresh embryo transfer (adjusted OR 3.65; 95%
      CI: 2.02-6.59) but not for thawed embryo transfer (adjusted OR 1.60; 95% CI: 0.69
      3.69). CONCLUSION: Our findings suggest that there is a specific risk of
      blastogenesis birth defects arising very early in pregnancy after IVF or ICSI and
      that this risk may be lower with use of frozen-thawed embryo transfer.

PMID- 19850592
TI  - Comparison of inhibin B and estradiol responses to intravenous FSH in women with
      polycystic ovary syndrome and normal women.
AB  - BACKGROUND: Inhibin B (Inh B) is produced by pre-antral and early antral
      follicles whereas estradiol (E(2)) is a product of follicles undergoing antrum
      formation. This temporal distinction is evident in the patterns of Inh B and E(2)
      release earlier and later during the follicular phase of the menstrual cycle,
      respectively. However, in previous studies of women with polycystic ovary
      syndrome (PCOS) and normal controls, release of these granulosa cell (GC)
      products appears to be simultaneous in response to FSH stimulation. In order to
      reconcile these disparate findings, we conducted dose-response studies in both
      PCOS women and normal controls to determine whether GC product responses were due
      to the amount of FSH administered. In addition, we compared FSH-stimulated
      responses in PCOS women at various stages of recovery following ovarian
      suppression with a long-acting GnRH agonist to examine whether Inh B and E(2)
      responses reflected the level of ovarian follicle activity (i.e. circulating E(2)
      levels). METHODS: Women with PCOS, 18-35 years (n = 23), and normal ovulatory
      controls, 18-35 years (n = 10) were recruited for study. Dose-responses were
      assessed over 24 h following intravenous administration of 0 (saline), 37.5, 75
      and 150 IU of recombinant human FSH (r-hFSH) in PCOS and normal women. In
      addition, E(2) and Inh B responses to 150 IU of r-hFSH were assessed at baseline
      and 4, 6 and 8 weeks following suppression of ovarian steroidogenesis by a long
      acting GnRH agonist in PCOS women. RESULTS: In PCOS women and normal controls,
      serum Inh B and E(2) exhibit similar and simultaneous dose-responsiveness to FSH
      stimulation. During recovery from ovarian suppression, basal and stimulated Inh B
      release appear to be restored earlier than that of E(2) in PCOS women.
      CONCLUSIONS: These findings are consistent with the notion that, in PCOS women,
      the level of ovarian follicle activity largely determines the earlier release of
      Inh B compared with E(2).

PMID- 19850593
TI  - Macroprolactin on the Advia Centaur: experience with 409 patients over a three
      year period.
AB  - INTRODUCTION: Macroprolactin (MPRL) is an important source of interference that
      may lead to misdiagnosis and mismanagement of hyperprolactinaemic patients.
      Prolactin assays exhibit considerable variation in the detection of MPRL. In this
      study, we examine the requirement for polyethylene glycol (PEG) precipitation in
      the analysis of hyperprolactinaemia detected by the Advia Centaur as it has a
      relatively low reactivity with MPRL. METHODS: Four hundreds and sixty-four
      hyperprolactinaemic samples were collected from the laboratory information system
      for Saint James University Hospital over a three-year period. These samples were
      screened for MPRL using PEG precipitation protocol. Monomeric prolactin
      concentration post-PEG precipitation was compared with a reference range
      determined by PEG precipitation in normal subjects. RESULTS: MPRL was the cause
      of hyperprolactinaemia in 4% of patients (16/409) over the three-year period
      studied. Nine subjects with MPRL also had elevated monomeric prolactin.
      CONCLUSIONS: PEG screening is still needed for assays with low MPRL reactivity
      such as the Advia Centaur and this should be performed with a locally derived
      reference range for monomeric prolactin.

PMID- 19850594
TI  - Can actigraphy measure sleep fragmentation in children?
AB  - OBJECTIVE: The gold standard assessment for sleep quality is polysomnography
      (PSG). However, actigraphy has gained popularity as an ambulatory monitor. We
      aimed to assess the value of actigraphy in measuring sleep fragmentation in
      children. METHODS: 130 children aged 2-18 years referred for assessment for sleep
      disordered breathing (SDB) were recruited. The arousal index (AI) scored from PSG
      was compared to the actigraphic fragmentation index (FI) and number of wake
      bouts/h. RESULTS: The ability of actigraphic measures to correctly classify a
      child as having an AI>10 events/h rated as fair for the FI and poor for wake
      bouts/h (area under the receiver operator characteristic curve, 0.73 and 0.67,
      respectively). CONCLUSION: Actigraphy provides only a fair indication of the
      level of arousal from sleep in children. While the limitations of actigraphy
      prevent it from being a diagnostic tool for SDB, it still has a role in
      evaluating sleep/wake schedules in children.

PMID- 19850595
TI  - A combined endovascular and open ''reverse hybrid'' technique for repair of
      complex juxtarenal inflammatory aortic aneurysms.
AB  - Inflammatory abdominal aortic aneurysms (IAAA) can present significant challenges
      to surgeons, especially in the juxtarenal location where they may not be amenable
      to endovascular repair. The dense, inflammatory component of these lesions can
      encase adjacent structures including the duodenum, ureters, and inferior vena
      cava putting them at risk for injury during open exposure. We report a novel
      ''reverse hybrid'' technique using a combined endovascular and open approach for
      repair of large, juxtarenal IAAA's.

PMID- 19850596
TI  - Effect of clopidogrel on perioperative blood loss and transfusion in coronary
      artery bypass graft surgery.
AB  - The effect of antiplatelet therapy (APT) on postoperative bleeding, transfusion
      needs and re-exploration remains unclear. This study examines the influence of
      APT, as well as antiplatelet mono- and combined therapy, on haemorrhage and
      transfusion requirements in patients undergoing coronary artery bypass on
      cardiopulmonary bypass (CPB). Six hundred and fifty patients were reviewed
      retrospectively, 325 patients received APT within seven days and 325 control
      patients. APT group had two subgroups: clopidogrel (CLO) group: n=48 patients
      received CLO as mono-therapy; combined group: n=277 patients received both CLO
      and aspirin (ASS). The mediastinal drainage at 12 h was control group: 505 ml+/
      445 ml and APT group: 802 ml+/-720 ml, P<0.001. APT group (vs. control group)
      received significantly more units of blood (3.9+/-4.2 vs. 1.9+/-2.6; P<0.001),
      platelet units (1.0+/-1.4 vs. 0.1+/-0.3; P<0.001), and fresh frozen plasma (FFP)
      units (2.9+/-3.9 vs. 0.9+/-2.2; P<0.001), respectively. Combined and mono-therapy
      groups had no significant differences in bleeding and blood transfusion.
      Considerations should be given to delaying elective coronary surgery for patients
      received APT for seven days.

PMID- 19850597
TI  - Right or left anterolateral minithoracotomy for repair of congenital ventricular
      septal defects in adult patients.
AB  - For most patients who present with ventricular septal defects (VSDs) in
      adulthood, the major concern is not the mortality or morbidity associated with
      repair surgery, but rather cosmetic problems arising from surgical scarring as a
      result of median sternotomy. From March 2005 to August 2008, nine patients
      (M:F=1:8) underwent repair of congenital VSD using right (n=7) or left (n=2)
      anterolateral minithoracotomy. We compared the perioperative data of these
      patients with that of the patients (n=8) who underwent VSD repair using median
      sternotomy during the same period. VSDs were of the perimembranous (n=6),
      subarterial (n=1), muscular inlet (n=1), and muscular outlet (n=1) type in
      minithoracotomy group. There was no in-hospital mortality in both groups. Mean
      cardiopulmonary bypass (CPB) time in minithoracotomy group was longer than that
      of sternotomy group (98.0+/-23.7 min vs. 68.5+/-13.3 min, P=0.011), but aorta
      cross-clamping (ACC) time was not different (45.9+/-20.0 min in minithoracotomy
      group vs. 40.5+/-12.1 min in sternotomy group) (P=0.481). There were no
      postoperative complications related to surgery or peripheral cannulation. The
      mean hospital stay was 3.6 days in minithoracotomy group and 6.1 days in
      sternotomy group, respectively (P=0.004). Minimally invasive cardiac surgery
      using minithoracotomy with peripheral cannulation can be safely applied to adult
      VSD patients irrespective of VSD type.

PMID- 19850598
TI  - Complete video-assisted thoracoscopic surgery lobectomy and its learning curve. A
      single center study introducing the technique in The Netherlands.
AB  - Data regarding the benefits for the complete video-assisted thoracic surgery (c
      VATS) lobectomy over the open lobectomy are numerous. This article describes the
      experience of introducing this technique in a training hospital, the first
      reported cohort in The Netherlands. From March 2006 to November 2008, all
      patients operated on for proven or suspected lung cancer were analyzed.
      Prospective data from these patients were evaluated. A subgroup analysis for the
      c-VATS lobectomy is presented. A total of 184 operations were performed on 172
      patients. In 122 (66.3%) of the operations the resection ended in a lobectomy of
      which 70 were done by complete thoracoscopic procedure. For the c-VATS lobectomy
      the mean operating time was 179 min, with a mean blood loss of 444 ml. The median
      hospital stay was four days. Complications were present in 10% of c-VATS
      lobectomies. No mortality was seen in the c-VATS group. After thorough evaluation
      and training, c-VATS lobectomy is a safe procedure that can be performed in a
      relatively low volume hospital. It has exceptional short-term benefits. For
      training purposes all operations must start thoracoscopically. All patients must
      be operated according the intention to treat method.

PMID- 19850599
TI  - Large mediastinal thoracic duct cyst.
AB  - Thoracic duct cysts of the mediastinum are extremely rare. The etiology is
      related to a congenital or degenerative weakness in the wall of the thoracic
      duct. Symptoms may arise from compression of adjacent structures. Surgical
      resection is recommended and allows a definitive histological diagnosis.
      Postoperative chylothorax is the most frequent complication. We describe a 30
      year-old female who presented to us with a history of dry cough and hiccups
      within the last four months.

PMID- 19850600
TI  - Adaption of suction connectors for use in meconium aspiration syndrome.
AB  - Severe meconium aspiration syndrome is difficult to manage and has a high
      mortality in developing countries. Guidelines are available for the initial
      management. If the infant has been born through particulate meconium and is not
      vigorous, an inspection of the vocal cords by laryngoscopy is recommended. If
      meconium is seen at the cords it should, ideally, be sucked out of the trachea
      using an endotracheal tube as a suction device. However, as this needs a way of
      applying suction directly to the endotracheal tube it can be problematic.
      Commercially available equipment does exist, but in a resource-scarce setting,
      its cost could be prohibitive. We have adapted cheap suction connectors which can
      be adapted for this purpose.

PMID- 19850601
TI  - Brucella endocarditis: a report from Iran.
AB  - Endocarditis is a rare focal complication of brucellosis but the most common
      cause of mortality. The diagnosis of the complications of endemic diseases is
      therefore important. We evaluated Brucella endocarditis cases in a teaching
      hospital in Iran between April 1998 and March 2006. Nine patients with a median
      age of 38.11 years were recorded, of whom seven (77.7%) were male. Underlying
      cardiopathy was present in three patients (33.3%). The median duration of the
      symptoms prior to diagnosis was 5.33 months. Endocarditis involved the aortic
      valve in six cases (66.6%), the mitral valve in two cases (22.2%) and the aortic
      valve plus the mitral valve in one case (11.1%). Serologic tests were positive in
      eight (88.8%) and blood culture was positive in two (22.2%). Aortic valve
      replacement surgery was undertaken for five patients (55.5%). One patient died
      due to arrhythmia. A high degree of suspicion is therefore necessary in order to
      ameliorate the course of Brucella endocarditis.

PMID- 19850602
TI  - Optical urethrotomy under local anaesthesia is a feasible option in urethral
      stricture disease.
AB  - The aim of our study was to assess the feasibility of performing optical
      urethrotomy for urethral stricture disease under local anaesthesia. A total of 33
      patients with radiologically proven urethral stricture underwent optical
      urethrotomy by a single operator under local anaesthesia. Of these patients, 23
      (70%) had stricture involving the corpora spongiosum and 18 (55%) of the patients
      were dependent on supra-pubic catheters. The procedure was successful in 30 cases
      (91%). The procedure was very well tolerated (average visual analogue pain score
      of 2/10) with an extremely low complication rate. The large number of patients
      with urethral stricture disease and the premium on operating time on formal
      theatre slates encouraged us to perform these procedures under local anaesthetic.
      Although most patients had severe stricture disease, the majority of cases were
      successful and very well tolerated. Optical urethrotomy under local anesthesia
      could be a viable option in the absence of formal theatre time and the facilities
      to perform general anaesthesia.

PMID- 19850603
TI  - Emergency peripartum hysterectomy in a tertiary hospital in Lagos, Nigeria: a
      five-year review.
AB  - This was a retrospective descriptive study of all the patients who underwent
      emergency peripartum hysterectomy from January 1st 2003 to December 31st 2007 at
      the Lagos State University Teaching Hospital. Of the 15,067 deliveries during the
      study period, 57 patients had emergency peripartum hysterectomy (3.78/1000
      deliveries). 19.3% of these patients were booked for antenatal care in the
      hospital, while 80.7% were unbooked. The mean age of patients was 32.7 years (SD
      = 5.5) and the mean parity was 3.08 (SD = 1.9). The major indications for
      emergency peripartum hysterectomy were ruptured uterus (77.2%), uterine atony
      (10.5%), abruptio placentae (3.5%) and sepsis (3.5%). Subtotal hysterectomy was
      performed in 96.5% of the cases. The maternal mortality was 19.3% and the
      perinatal mortality was 75.4%. The incidence of emergency peripartum hysterectomy
      in this study is high and the major indication is ruptured uterus. It is
      associated with high maternal and perinatal morbidity and mortality.

PMID- 19850604
TI  - Amoebic liver abscess: experience in a south Asian country.
AB  - Amoebic liver abscess (ALA) is endemic in south Asian countries. The current
      study was undertaken in order to evaluate the clinical spectrum, management and
      outcome of ALA at an urban tertiary care hospital in Pakistan. The chart notes of
      232 ALA patients admitted from 1 January 2000 to 31 August 2007 were
      retrospectively reviewed. The most frequent clinical findings included: fever
      (96.5%); right upper abdomen pain (80.2%); liver tenderness (73.5%); tachycardia
      (61.6%); hepatomegaly (60%); nausea and vomiting (42%); and jaundice (23.9%). The
      duration of symptoms was less than 14 days in 70% . Ultrasound examinations
      revealed 69% of the abscesses were in the right lobe, 19% in the left lobe and
      12% in both lobes. The size of the abscess was greater than 5.0 cm in 83%.
      Seventy-seven percent of the patients had a single abscess and 23% had multiple
      abscesses. Ultrasound-guided therapeutic aspiration was performed in 64%, but 36%
      were treated with antibiotics alone. Metronodazole was the most frequently used
      antibiotic. However, various combinations of antibiotics were also used without
      any obvious justification.

PMID- 19850606
TI  - A simple technique for the placement of Schanz screws into bone using minimal
      radiologic control.
AB  - The insertion of Schanz screws into the bone during external-fixation procedures
      in trauma and elective orthopaedic surgery is usually done under roentgenologic
      control. In order to minimize irradiation exposure for the patients, as well as
      surgeons, we describe a simple method of Schanz screw placement. The
      roentgenologic control of the position of the half-pins is only necessary at the
      beginning and the end of the procedure. This technique is simple, shortens the
      operating time and reduces the amount of radiation exposure to both the patient
      and surgeon. It is a valuable technique in many resource-poor environments who do
      not have the facilities for an image intensifier fluoroscopy or C-arm as well as
      in austere situations such as during military operations.

PMID- 19850605
TI  - The clinical profile and predictors of mortality in patients with melioidosis in
      South India.
AB  - Melioidosis is an underdiagnosed and underreported disease in India with protean
      clinical manifestations. Mortality in this study population was 17%. The
      predominant risk factor for melioidosis was diabetes mellitus. Multifocal disease
      was present in 66% and pulmonary involvement in 61% of patients. In a country
      like India where the conditions are conducive for endemic melioidosis and due to
      the clinical similarity of melioidosis to diseases like tuberculosis, it is
      essential for clinicians to have a high degree of suspicion and pursue suitable
      diagnostic strategies for melioidosis in the appropriate clinical setting.

PMID- 19850607
TI  - Diagnostic utility of a single Widal test in the diagnosis of typhoid fever at
      Aga Khan University Hospital (AKUH), Nairobi, Kenya.
AB  - Typhoid fever is a systemic illness caused by Salmonella enterica serovar typhi
      (S. typhi) and is endemic in Kenya, where a single Widal test done on an acute
      phase serum is the most commonly used test. Using a cut-off value of 1:320 for
      both O and H agglutinins as being diagnostic of S. typhi, only 18 (26%) of our
      patients had diagnostic titres; 37 (53.6%) had O and H titres less than 1:40. Our
      study showed that Widal testing done on an acute phase serum of a patient
      suspected to have typhoid fever had limited diagnostic capability given its low
      sensitivity.

PMID- 19850608
TI  - Abdominal wall hernia repair in cirrhotic patients: outcomes seen at a tertiary
      care hospital in a developing country.
AB  - The outcome of hernia repair in patients with cirrhosis remains poor when
      compared to non-cirrhotics. The aim of our study was to evaluate the outcome of
      hernia repair in cirrhotic patients at our tertiary care hospital located in a
      developing country. A total of 61 patients with cirrhosis underwent hernia repair
      from January 2001 to December 2007 at our hospital. The mean age of the patients
      was 52 years and there were 30 males. Early postoperative complications were
      noted in 20 (33%) patients including two mortalities. The incidence of early
      complications was higher (71%) in patients with Child class C cirrhosis as
      compared to patients with either Child class A or B cirrhosis (21%), and the
      difference was statistically significant (P < 0.001). Except in emergency
      circumstances, surgery in Child class C patients may either be delayed until the
      patient is medically optimized or performed early before liver disease progresses
      to severe decompensation.

PMID- 19850609
TI  - Should healthy volunteers in clinical trials be paid according to risk? Yes.

PMID- 19850610
TI  - Should healthy volunteers in clinical trials be paid according to risk? No.

PMID- 19850611
TI  - Sugar source modulates exopolysaccharide biosynthesis in Bifidobacterium longum
      subsp. longum CRC 002.
AB  - The effect of four sugars (glucose, galactose, lactose and fructose) on
      exopolysaccharide (EPS) production by Bifidobacterium longum subsp. longum CRC
      002 was evaluated. More EPS was produced when CRC 002 was grown on lactose in the
      absence of pH control, with a production of 1080+/-120 mg EPS l(-1) (P<0.01)
      after 24 h of incubation. For fructose, galactose and glucose, EPS production was
      similar, at 512+/-63, 564+/-165 and 616+/-93 mg EPS l(-1), respectively. The
      proposed repeating unit composition of the EPS is 2 galactose to 3 glucose. The
      effect of sugar and fermentation time on expression of genes involved in sugar
      nucleotide production ( galK, galE1, galE2, galT1, galT2, galU, rmlA, rmlB1 and
      rmlCD) and the priming glycosyltransferase ( wblE) was quantified using real-time
      reverse transcription PCR. A significantly higher transcription level of wblE
      (9.29-fold) and the genes involved in the Leloir pathway (galK, 4.10-fold; galT1,
      2.78-fold; and galE2, 4.95-fold) during exponential growth was associated with
      enhanced EPS production on lactose compared to glucose. However, galU expression,
      linking glucose metabolism with the Leloir pathway, was not correlated with EPS
      production on different sugars. Genes coding for dTDP-rhamnose biosynthesis were
      also differentially expressed depending on sugar source and growth phase,
      although rhamnose was not present in the composition of the EPS. This precursor
      may be used in cell wall polysaccharide biosynthesis. These results contribute to
      understanding the changes in gene expression when different sugar substrates are
      catabolized by B. longum subsp. longum CRC 002.

PMID- 19850612
TI  - Transcriptional and functional characterization of the gene encoding acyl carrier
      protein in Bacillus subtilis.
AB  - Acyl carrier protein (ACP) is a universal and highly conserved carrier of acyl
      intermediates during fatty acid biosynthesis. The molecular mechanisms of
      regulation of the acpP structural gene, as well as the function of its gene
      product, are poorly characterized in Bacillus subtilis and other Gram-positive
      organisms. Here, we report that transcription of acpP takes place from two
      different promoters: PfapR and PacpP. Expression of acpP from PfapR is
      coordinated with a cluster of genes involved in lipid synthesis (the fapR
      operon); the operon consists of fapR-plsX-fabD-fabG-acpP. PacpP is located
      immediately upstream of the acpP coding sequence, and is necessary and sufficient
      for normal fatty acid synthesis. We also report that acpP is essential for growth
      and differentiation, and that ACP localizes in the mother-cell compartment of the
      sporangium during spore formation. These results provide the first detailed
      characterization of the expression of the ACP-encoding gene in a Gram-positive
      bacterium, and highlight the importance of this protein in B. subtilis
      physiology.

PMID- 19850613
TI  - Molecular typing of Mycobacterium intracellulare using multilocus variable-number
      of tandem-repeat analysis: identification of loci and analysis of clinical
      isolates.
AB  - In addition to its known status as a disseminated disease in HIV-positive
      patients, Mycobacterium avium complex (MAC) is increasingly recognized as a
      causative pathogen of respiratory disease in HIV-negative patients. MAC is
      divided into Mycobacterium avium, and the less-epidemiologically studied
      Mycobacterium intracellulare. Genetic typing for M. intracellulare using variable
      number of tandem repeats (VNTR) has not yet been developed. The aim of this study
      was to identify VNTR loci in the genome of M. intracellulare and apply them as an
      epidemiological tool to clinical isolates. Here, we identified 25 VNTR loci on
      the M. intracellulare genome, of which 16 showed variations among clinical
      isolates in the number of tandem repeat motifs. Among the 74 M. intracellulare
      isolates, 50 genotypes were distinguished using the 16 VNTR loci, resulting in a
      Hunter Gaston's discriminatory index of 0.988. Moreover, all 16 VNTR loci were
      stable in different sets of isolates recovered within time intervals ranging from
      2 to 1551 days from 14 separate patients. These results indicate that for use as
      epidemiological markers of M. intracellulare, the loci in this VNTR assay are
      highly discriminating and stable over time.

PMID- 19850614
TI  - Study of the distribution of autotrophic CO2 fixation cycles in Crenarchaeota.
AB  - Two new autotrophic carbon fixation cycles have been recently described in
      Crenarchaeota. The 3-hydroxypropionate/4-hydroxybutyrate cycle using acetyl
      coenzyme A (CoA)/propionyl-CoA carboxylase as the carboxylating enzyme has been
      identified for (micro)aerobic members of the Sulfolobales. The dicarboxylate/4
      hydroxybutyrate cycle using oxygen-sensitive pyruvate synthase and
      phosphoenolpyruvate carboxylase as carboxylating enzymes has been found in
      members of the anaerobic Desulfurococcales and Thermoproteales. However,
      Sulfolobales include anaerobic and Desulfurococcales aerobic autotrophic
      representatives, raising the question of which of the two cycles they use. We
      studied the mechanisms of autotrophic CO(2) fixation in the strictly anaerobic
      Stygiolobus azoricus (Sulfolobales) and in the facultatively aerobic Pyrolobus
      fumarii (Desulfurococcales). The activities of all enzymes of the 3
      hydroxypropionate/4-hydroxybutyrate cycle were found in the anaerobic S.
      azoricus. In contrast, the aerobic or denitrifying P. fumarii possesses all
      enzyme activities of the dicarboxylate/4-hydroxybutyrate cycle. We conclude that
      autotrophic Crenarchaeota use one of the two cycles, and that their distribution
      correlates with the 16S rRNA-based phylogeny of this group, rather than with the
      aerobic or anaerobic lifestyle.

PMID- 19850615
TI  - Purification and characterization of a clostripain-like protease from a
      recombinant Clostridium perfringens culture.
AB  - Clostridium perfringens produces a homologue of clostripain (Clo), the arginine
      specific endopeptidase of Clostridium histolyticum. To determine the biochemical
      and biological properties of the C. perfringens homologue (Clp), it was purified
      from the culture supernatant of a recombinant C. perfringens strain by cation
      exchange chromatography and ultrafiltration. Analysis by SDS-PAGE, N-terminal
      amino acid sequencing and TOF mass spectrometry revealed that Clp consists of two
      polypeptides comprising heavy (38 kDa) and light (16 kDa or 15 kDa) chains, and
      that the two light chains differ in the N-terminal cleavage site. This difference
      in the light chain did not affect the enzymic activity toward N-benzoyl-l
      arginine p-nitroanilide (Bz-l-arginine pNA), as demonstrated by assaying culture
      supernatants differing in the relative ratio of the two light chains. Although
      the purified Clp preferentially degraded Bz-dl-arginine pNA rather than Bz-dl
      lysine pNA, it degraded the latter more efficiently than did Clo. Clp showed 2.3
      fold higher caseinolytic activity than Clo, as expected from the difference in
      substrate specificity. Clp caused an increase in vascular permeability when
      injected intradermally into mice, implying a possible role of Clp in the
      pathogenesis of clostridial myonecrosis.

PMID- 19850616
TI  - Hydrophobic carboxy-terminal residues dramatically reduce protein levels in the
      haloarchaeon Haloferax volcanii.
AB  - Proteolysis is important not only to cell physiology but also to the successful
      development of biocatalysts. While a wide-variety of signals are known to trigger
      protein degradation in bacteria and eukaryotes, these mechanisms are poorly
      understood in archaea, known for their ability to withstand harsh conditions.
      Here we present a systematic study in which single C-terminal amino acid residues
      were added to a reporter protein and shown to influence its levels in an archaeal
      cell. All 20 amino acid residues were examined for their impact on protein
      levels, using the reporter protein soluble modified red-shifted GFP (smRS-GFP)
      expressed in the haloarchaeon Haloferax volcanii as a model system. Addition of
      hydrophobic residues, including Leu, Cys, Met, Phe, Ala, Tyr, Ile and Val, gave
      the most pronounced reduction in smRS-GFP levels compared with the addition of
      either neutral or charged hydrophilic residues. In contrast to the altered
      protein levels, the C-terminal alterations had no influence on smRS-GFP-specific
      transcript levels, thus revealing that the effect is post-transcriptional.

PMID- 19850617
TI  - Regulation of the dauBAR operon and characterization of D-amino acid
      dehydrogenase DauA in arginine and lysine catabolism of Pseudomonas aeruginosa
      PAO1.
AB  - A unique D-to-L racemization of arginine by coupled arginine dehydrogenases DauA
      and DauB encoded by the dauBAR operon has been recently reported as a
      prerequisite for D-arginine utilization as the sole source of carbon and nitrogen
      through L-arginine catabolic pathways in P. aeruginosa. In this study, enzymic
      properties of the catabolic FAD-dependent d-amino acid dehydrogenase DauA and the
      physiological functions of the dauBAR operon were further characterized with
      other d-amino acids. These results establish DauA as a D-amino acid dehydrogenase
      of broad substrate specificity, with D-Arg and D-Lys as the two most effective
      substrates, based on the kinetic parameters. In addition, expression of dauBAR is
      specifically induced by exogenous D-Arg and D-Lys, and mutations in the dauBAR
      operon affect utilization of these two amino acids alone. The function of DauR as
      a repressor in the control of the dauBAR operon was demonstrated by dauB promoter
      activity measurements in vivo and mobility shift assays with purified His-tagged
      protein in vitro. The potential effect of 2-ketoarginine (2-KA) derived from D
      Arg deamination by DauA as a signal molecule in dauBAR induction was first
      revealed by mutation analysis and further supported by its in vitro effect on
      alleviation of DauR-DNA interactions. Through sequence analysis, putative DauR
      operators were identified and confirmed by mutation analysis. Induction of the
      dauBAR operon to the maximal level was found to require the L-arginine-responsive
      regulator ArgR, as supported by the loss of inductive effect by L-Arg on dauBAR
      expression in the argR mutant and binding of purified ArgR to the dauB regulatory
      region in vitro. In summary, this study establishes that optimal induction of the
      dauBAR operon requires relief of DauR repression by 2-KA and activation of ArgR
      by L-Arg as a result of d-Arg racemization by the encoded DauA and DauB.

PMID- 19850618
TI  - The hrcA and hspR regulons of Campylobacter jejuni.
AB  - The human pathogen Campylobacter jejuni has a classic heat shock response,
      showing induction of chaperones and proteases plus several unidentified proteins
      in response to a small increase in growth temperature. The genome contains two
      homologues to known heat shock response regulators, HrcA and HspR. Previous work
      has shown that HspR controls several heat-shock genes, but the hrcA regulon has
      not been defined. We have constructed single and double deletions of C. jejuni
      hrcA and hspR and analysed gene expression using microarrays. Only a small number
      of genes are controlled by these two regulators, and the two regulons overlap.
      Strains mutated in hspR, but not those mutated in hrcA, showed enhanced
      thermotolerance. Some genes previously identified as being downregulated in a
      strain lacking hspR showed no change in expression in our experiments.

PMID- 19850619
TI  - Characterization of a virulence-associated and cell-wall-located DNase of
      Streptococcus pyogenes.
AB  - We investigated culture supernatant proteins from the M1 serotype of
      Streptococcus pyogenes by two-dimensional gel electrophoresis and peptide mass
      mapping analysis, and characterized the single protein spots. Among them, we
      analysed the Spy0747 protein. This protein is homologous to the SsnA protein, a
      cell-wall-located DNase expressed in Streptococcus suis serotype 2. We designated
      the Spy0747 protein as SpnA. SpnA protein was also detected in the insoluble
      fraction of whole-cell lysates using shotgun proteomic analysis, suggesting that
      SpnA is also located in the cell wall. SpnA was expressed as a glutathione S
      transferase-fusion protein in Escherichia coli. We confirmed that the recombinant
      protein had DNase activity that was dependent on Ca(2+) and Mg(2+), like SsnA.
      Blood bactericidal assays and mouse infection model experiments showed that the
      spnA knockout strain was less virulent than the parental strain, thus suggesting
      that SpnA could play an important role in virulence. Using PCR, we found that the
      spnA gene was present in all clinical S. pyogenes strains we examined. Our
      results, together with a previous report identifying Spy0747 as a surface
      associated protein, suggest that SpnA is an important cell-wall-located DNase
      that is generally produced in S. pyogenes and is involved in virulence.

PMID- 19850620
TI  - New insights into the regulatory networks of paralogous genes in bacteria.
AB  - Extensive genomic studies on gene duplication in model organisms such as
      Escherichia coli and Saccharomyces cerevisiae have recently been undertaken. In
      these models, it is commonly considered that a duplication event may include a
      transcription factor (TF), a target gene, or both. Following a gene duplication
      episode, varying scenarios have been postulated to describe the evolution of the
      regulatory network. However, in most of these, the TFs have emerged as the most
      important and in some cases the only factor shaping the regulatory network as the
      organism responds to a natural selection process, in order to fulfil its
      metabolic needs. Recent findings concerning the regulatory role played by
      elements other than TFs have indicated the need to reassess these early models.
      Thus, we performed an exhaustive review of paralogous gene regulation in E. coli
      and Bacillus subtilis based on published information, available in the NCBI
      PubMed database and in well-established regulatory databases. Our survey
      reinforces the notion that despite TFs being the most prominent components
      shaping the regulatory networks, other elements are also important. These include
      small RNAs, riboswitches, RNA-binding proteins, sigma factors, protein-protein
      interactions and DNA supercoiling, which modulate the expression of genes
      involved in particular metabolic processes or induce a more complex response in
      terms of the regulatory networks of paralogous genes in an integrated interplay
      with TFs.

PMID- 19850621
TI  - Fungal physiology and the origins of molecular biology.
AB  - Molecular biology has several distinct origins, but especially important are
      those contributed by fungal and yeast physiology, biochemistry and genetics. From
      the first gene action studies that became the basis of our understanding of the
      relationship between genes and proteins, through chromosome structure,
      mitochondrial genetics and membrane biogenesis, gene silencing and circadian
      clocks, studies with these organisms have yielded basic insight into these
      processes applicable to all eukaryotes. Examples are cited of pioneering studies
      with fungi that have stimulated new research in clinical medicine and
      agriculture; these studies include sexual interactions, cell stress responses,
      the cytoskeleton and pathogenesis. Studies with the yeasts and fungi have been
      effective in applying the techniques and insights gained from other types of
      experimental systems to research in fungal cell signalling, cell development and
      hyphal morphogenesis.

PMID- 19850622
TI  - Fungal physiology - a future perspective.
AB  - The study of fungal physiology is set to change dramatically in the next few
      years as highly scalable technologies are deployed allowing accurate measurement
      and identification of metabolites, proteins and transcripts within cells. The
      advent of next-generation DNA-sequencing technologies will also provide genome
      sequence information from large numbers of industrially relevant and pathogenic
      fungal species, and allow comparative genome analysis between strains and
      populations of fungi. When coupled with advances in gene functional analysis,
      protein-protein interaction studies, live cell imaging and mathematical
      modelling, this promises a step-change in our understanding of how fungal cells
      operate as integrated dynamic living systems.

PMID- 19850623
TI  - Genetic determinants of Pseudomonas aeruginosa biofilm establishment.
AB  - The establishment of bacterial biofilms on surfaces is a complex process that
      requires various factors for each consecutive developmental step. Here we report
      the screening of the comprehensive Harvard Pseudomonas aeruginosa PA14 mutant
      library for mutants exhibiting an altered biofilm phenotype. We analysed the
      capability of all mutants to form biofilms at the bottom of a 96-well plate by
      the use of an automated confocal laser-scanning microscope and found 394 and 285
      genetic determinants of reduced and enhanced biofilm production, respectively.
      Overall, 67 % of the identified mutants were affected within genes encoding
      hypothetical proteins, indicating that novel developmental pathways are likely to
      be dissected in the future. Nevertheless, a common theme that emerged from the
      analysis of the genes with a predicted function is that the establishment of a
      biofilm requires regulatory components that are involved in survival under
      microaerophilic growth conditions, arginine metabolism, alkyl-quinolone
      signalling, pH homeostasis and the DNA repair system.

PMID- 19850624
TI  - Assessment of in vivo genotoxicity of the rodent carcinogen furan: evaluation of
      DNA damage and induction of micronuclei in mouse splenocytes.
AB  - In recent years, several surveys have highlighted the presence of the rodent
      carcinogen furan in a variety of food items. Even though the evidence of
      carcinogenicity of furan is unequivocal, the underlying mechanism has not been
      fully elucidated. In particular, the role of genotoxicity in furan
      carcinogenicity is still not clear, even though this information is considered
      pivotal for the assessment of the risk posed by the presence of low doses of
      furan in food. In this work, the genotoxic potential of furan in vivo has been
      investigated in mice, under exposure conditions similar to those associated with
      cancer onset in the National Toxicology Program long-term bioassay. To this aim,
      male B6C3F1 mice were treated by gavage for 4 weeks with 2, 4, 8 and 15 mg
      furan/kg b.w./day. Spleen was selected as the target organ for genotoxicity
      assessment, in view of the capability of quiescent splenocytes to accumulate DNA
      damage induced by repeat dose exposure. The induction of primary DNA damage in
      splenocytes was evaluated by alkaline single-cell gel electrophoresis (comet
      assay) and by the immunofluorescence detection of foci of phosphorylated histone
      H2AX (gamma-H2AX). The presence of cross-links was probed in a modified comet
      assay, in which cells were irradiated in vitro with gamma-rays before
      electrophoresis. Chromosome damage was quantitated through the detection of
      micronuclei in mitogen-stimulated splenocytes using the cytokinesis-block method.
      Micronucleus induction was also assessed with a modified protocol, using the
      repair inhibitor 1-beta-arabinofuranosyl-cytosine to convert single-strand breaks
      in micronuclei. The results obtained show a significant (P < 0.01) increase of
      gamma-H2AX foci in mitogen-stimulated splenocytes of mice treated with 8 and 15
      mg furan/kg b.w. and a statistically significant (P < 0.001) increases of
      micronuclei in binucleated splenocytes cultured in vitro. Conversely, no effect
      of in vivo exposure to furan was observed when freshly isolated quiescent
      splenocytes were analysed by immunofluorescence and in comet assays, both with
      standard and radiation-modified protocols. These results indicate that the in
      vivo exposure to furan gives rise to pre-mutagenic DNA damage in resting
      splenocytes, which remains undetectable until it is converted in frank lesions
      during the S-phase upon mitogen stimulation. The resulting DNA strand breaks are
      visualized by the increase in gamma-H2AX foci and may originate micronuclei at
      the subsequent mitosis.

PMID- 19850625
TI  - "Proportion explained": a causal interpretation for standard measures of indirect
      effect?
AB  - The assessment of indirect effects is an important tool for epidemiologists
      interested in exploring the mechanisms of exposure-disease relations. A standard
      way of expressing an indirect effect is in terms of the "proportion explained";
      this is the proportion of the total effect that is explained by a particular
      mediator (or set of mediators). There are several ways to calculate the
      proportion explained, based on both additive and multiplicative models. However,
      these standard methods (particularly those based on multiplicative models) have
      been criticized for lacking a causal interpretation. To address this issue, the
      author uses a framework of potential outcomes to define the indirect effects of
      interest (natural effects) and assess the correspondence between the natural
      effects and standard measures. The author finds that standard additive measures
      represent an unbiased weighted average of the effects of interest; standard
      multiplicative measures, on the other hand, yield a biased weighted average of
      these effects. If the investigator is primarily interested in whether or not an
      indirect effect exists, standard measures for mediation will often yield the
      correct answer. In contrast, if valid quantification of the indirect effect is
      desired, counterfactual-based methods should be used.

PMID- 19850626
TI  - Physical activity's impact on the association of fat and fiber intake with
      survival after breast cancer.
AB  - This study examined whether, after a breast cancer diagnosis, high intake of
      animal fat was associated with increased breast cancer mortality and high intake
      of fiber was associated with decreased breast cancer mortality. Participants were
      3,846 US female nurses diagnosed with stages I-III breast cancer between 1976 and
      2001 and followed until death or May 2006. Breast cancer mortality was calculated
      according to dietary intake quintiles first assessed at least 12 months after
      diagnosis and was cumulatively averaged and updated. There were 446 breast cancer
      deaths. In simple models adjusted for time since diagnosis, age, and energy
      intake, animal fat intake was associated with increased breast cancer death, and
      cereal fiber intake was associated with reduced breast cancer death. However, no
      associations were found in fully adjusted models: for animal fat, the relative
      risks for increasing quintiles were 1.00, 0.89, 0.86, 0.85, and 0.89 (95%
      confidence interval: 0.61, 1.28), P = 0.68; for cereal fiber, they were 1.00,
      0.95, 0.76, 0.81, and 1.00 (95% confidence interval: 0.71, 1.40), P = 0.59.
      Results of simple models adjusted additionally for physical activity were similar
      to those for full multivariate models. Results show that physical activity
      strongly confounds the association between diet and survival.

PMID- 19850627
TI  - Newly reported respiratory symptoms and conditions among military personnel
      deployed to Iraq and Afghanistan: a prospective population-based study.
AB  - Concerns about respiratory conditions have surfaced among persons deployed to
      Iraq and Afghanistan. Data on 46,077 Millennium Cohort Study participants who
      completed baseline (July 2001-June 2003) and follow-up (June 2004-February 2006)
      questionnaires were used to investigate 1) respiratory symptoms (persistent or
      recurring cough or shortness of breath), 2) chronic bronchitis or emphysema, and
      3) asthma. Deployers had a higher rate of newly reported respiratory symptoms
      than nondeployers (14% vs. 10%), while similar rates of chronic bronchitis or
      emphysema (1% vs. 1%) and asthma (1% vs. 1%) were observed. Deployment was
      associated with respiratory symptoms in both Army (adjusted odds ratio = 1.73,
      95% confidence interval: 1.57, 1.91) and Marine Corps (adjusted odds ratio =
      1.49, 95% confidence interval: 1.06, 2.08) personnel, independently of smoking
      status. Deployment length was linearly associated with increased symptom
      reporting in Army personnel (P < 0.0001). Among deployers, elevated odds of
      symptoms were associated with land-based deployment as compared with sea-based
      deployment. Although respiratory symptoms were associated with deployment,
      inconsistency in risk with cumulative exposure time suggests that specific
      exposures rather than deployment in general are determinants of postdeployment
      respiratory illness. Significant associations seen with land-based deployment
      also imply that exposures related to ground combat may be important.

PMID- 19850628
TI  - The delta9 fatty acid desaturation index as a predictor of metabolic disease.

PMID- 19850630
TI  - Thirty-year multivariate risk assessment is a stronger predictor of
      cardiovascular disease than the 10-year model.

PMID- 19850629
TI  - Noninvasive prenatal detection of trisomy 21 by an epigenetic-genetic chromosome
      dosage approach.
AB  - BACKGROUND: The use of fetal DNA in maternal plasma for noninvasive prenatal
      diagnosis of trisomy 21 (T21) is an actively researched area. We propose a novel
      method of T21 detection that combines fetal-specific epigenetic and genetic
      markers. METHODS: We used combined bisulfite restriction analysis to search for
      fetal DNA markers on chromosome 21 that were differentially methylated in the
      placenta and maternal blood cells and confirmed any target locus with bisulfite
      sequencing. We then used methylation-sensitive restriction endonuclease digestion
      followed by microfluidics digital PCR analysis to investigate the identified
      marker. Chromosome-dosage analysis was performed by comparing the dosage of this
      epigenetic marker with that of the ZFY (zinc finger protein, Y-linked) gene on
      chromosome Y. RESULTS: The putative promoter of the HLCS (holocarboxylase
      synthetase) gene was hypermethylated in the placenta and hypomethylated in
      maternal blood cells. A chromosome-dosage comparison of the hypermethylated HLCS
      and ZFY loci could distinguish samples of T21 and euploid placental DNA. Twenty
      four maternal plasma samples from euploid pregnancies and 5 maternal plasma
      samples from T21 pregnancies were analyzed. All but 1 of the euploid samples were
      correctly classified. CONCLUSIONS: The epigenetic-genetic chromosome-dosage
      approach is a new method for noninvasive prenatal detection of T21. The
      epigenetic part of the analysis can be applied to all pregnancies. Because the
      genetic part of the analysis uses paternally inherited, fetal-specific genetic
      markers that are abundant in the genome, broad population coverage should be
      readily achievable. This approach has the potential to become a generally usable
      technique for noninvasive prenatal diagnosis.

PMID- 19850631
TI  - Preliminary proficiency testing results for succinylacetone in dried blood spots
      for newborn screening for tyrosinemia type I.
AB  - BACKGROUND: Succinylacetone (SUAC) is the primary metabolite accumulated in
      tyrosinemia type I--an inborn error of metabolism that, if untreated, can cause
      death from liver failure during the first months of life. Newborn screening
      laboratories measure SUAC in dried blood spot (DBS) samples to detect
      asymptomatic tyrosinemia type I. We used panels of SUAC-enriched DBSs to compare
      and evaluate the performance of these screening tests. METHODS: We prepared sets
      of DBS materials enriched with predetermined SUAC concentrations and distributed
      samples of these materials, along with a screening practices questionnaire, to
      laboratories that perform SUAC tests. We compared their reported SUAC
      concentrations and questionnaire responses to identify screening practices that
      affect SUAC test outcomes. RESULTS: Data from 2 pilot surveys showed large
      differences among laboratories in SUAC recoveries, reproducible within-laboratory
      recoveries, and stable performance of the DBS materials. Results from 257
      proficiency test analyses contained a total of 6 false-negative
      misclassifications. Reported recoveries of added SUAC ranged from 0 to >200%. Low
      biased SUAC recoveries were associated with 1 method used by 5 laboratories. All
      laboratories that reported SUAC recoveries > or =100% used DBS matrix
      calibrators. CONCLUSIONS: The wide ranges of SUAC concentrations reported for
      pilot and proficiency testing specimens demonstrate a need to harmonize
      quantitative results among laboratories. Although DBS matrix calibrators are
      important for optimizing SUAC recoveries, the preparation of these calibrators is
      not standardized among laboratories. Certified DBS-based SUAC calibrators are
      needed for accuracy and harmonization.

PMID- 19850632
TI  - Cerebrospinal fluid secretory Ca2+-dependent phospholipase A2 activity is
      increased in Alzheimer disease.
AB  - BACKGROUND: The phospholipase A(2) (PLA2) family comprises multiple isoenzymes
      that vary in their physicochemical properties, cellular localizations, calcium
      sensitivities, and substrate specificities. Despite these differences, PLA2s
      share the ability to catalyze the synthesis of the precursors of the
      proinflammatory mediators. To investigate the potential of PLA2 as a biomarker in
      screening neuroinflammatory disorders in both clinical and research settings, we
      developed a PLA2 assay and determined the predominant types of PLA2 activity in
      cerebrospinal fluid (CSF). METHODS: We used liposomes composed of a fluorescent
      probe (bis-Bodipy FL C11-PC [1,2-bis-(4,4- difluoro-5,7-dimethyl-4-bora-3a,4a
      diaza-s-indacene-3-undecanoyl)-sn-glycero-3-phosphocholine]) and 1,2-dioleoyl-l
      alpha-phosphatidylcholine as a substrate to measure CSF PLA2 activity in a 96
      well microtiter plate format. We established the type of CSF PLA2 activity using
      type-specific inhibitors of PLA2. RESULTS: Using 5 microL CSF per assay, our PLA2
      activity assay was reproducible with CVs <15% in 2 CSF samples and for
      recombinant secretory Ca(2+)-dependent PLA2 (sPLA2) in concentrations ranging
      from 0.25 to 1 micromol/L. This PLA2 assay allowed identification of sPLA2
      activity in lumbar CSF from healthy individuals 20-77 years old that did not
      depend on either sex or age. Additionally, CSF sPLA2 activity was found to be
      increased (P = 0.0008) in patients with Alzheimer disease. CONCLUSIONS: Adult
      human CSF has sPLA2 activity that can be measured reliably with the assay
      described. This enzyme activity in the CSF is independent of both sex and age and
      might serve as a valuable biomarker of neuroinflammation, as we demonstrated in
      Alzheimer disease.

PMID- 19850633
TI  - The ELISA, enzyme-linked immunosorbent assay.

PMID- 19850634
TI  - Hepatic lipid composition and stearoyl-coenzyme A desaturase 1 mRNA expression
      can be estimated from plasma VLDL fatty acid ratios.
AB  - BACKGROUND: Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the limiting step
      of monounsaturated fatty acid synthesis in humans and is an important player in
      triglyceride generation. SCD1 has been repeatedly implicated in the pathogenesis
      of metabolic and inflammatory diseases. Therefore it is of great importance to
      determine SCD1 activity in human samples. In this study we aimed to evaluate a
      hepatic SCD1 activity index derived from plasma VLDL triglyceride composition as
      a tool to estimate hepatic SCD1 expression in humans. Additionally, we further
      evaluated commonly used fatty acid ratios [elongase, de novo lipogenesis, and
      Delta5 and Delta6 desaturase] in plasma VLDL and hepatic lipid fractions. DESIGN
      AND METHODS: Liver biopsies and plasma samples were simultaneously collected from
      15 individuals. Plasma VLDL was obtained by ultracentrifugation. Hepatic and
      plasma VLDL lipids were fractionated by thin-layer chromatography, and the fatty
      acid composition of each fraction was analyzed by gas chromatography. Hepatic
      SCD1 expression was determined by real-time PCR. RESULTS: Hepatic SCD1 mRNA
      expression was associated with the product/precursor ratios (16:1/16:0 and
      18:1/18:0) of hepatic lipid fractions. The 16:1/16:0 ratio in hepatic and VLDL
      triglycerides as well as the 18:1/18:0 ratio in plasma VLDL were closely
      associated with hepatic SCD1 expression. The hepatic de novo lipogenesis index
      from triglycerides was associated with expression of lipogenic genes [fatty acid
      synthase (FASN), acetyl-Coenzyme A carboxylase alpha (ACACA), and sterol
      regulatory element binding transcription factor 1 (SREBP-1)] and is closely
      reflected by the de novo lipogenesis index in VLDL triglycerides. CONCLUSION: We
      demonstrated for the first time that hepatic SCD1 expression can be estimated
      noninvasively from routine blood samples by measuring the SCD1 activity index in
      fasting plasma VLDL.

PMID- 19850635
TI  - EGF61A>G polymorphism as predictive marker of clinical outcome to first-line
      capecitabine and oxaliplatin in metastatic colorectal cancer.
AB  - BACKGROUND: The purpose of the present study was to investigate polymorphisms
      related to the metabolism of fluoropyrimidine and oxaliplatin, thymidylate
      synthase (TS) and excision repair cross-complementing gene 1 (ERCC1) 118, in
      metastatic colorectal cancer patients treated with capecitabine and oxaliplatin
      (XELOX). We also investigated the importance of the EGF61A>G polymorphism, which
      holds a functional influence on the tyrosine kinase receptor regulation.
      MATERIALS AND METHODS: We included 68 patients treated with first-line XELOX.
      Polymorphism analyses were carried out on pretreatment blood samples. Response
      was evaluated according to the RECIST. Survival analysis was described by the
      Kaplan-Meier method and log-rank testing. RESULTS: The overall response rate was
      38% and the median overall survival 19.4 months. A favorable outcome was seen in
      patients with the EGF61A/G genotype compared with the combined group of A/A and
      G/G, with response rates of 57% and 18%, respectively (P = 0.001). There was a
      significantly different progression-free survival (P = 0.018) in favor of the A/G
      group. The TS and ERCC1 genotypes failed to provide any significant impact on the
      outcome. CONCLUSION: Polymorphism analysis of a simple blood sample is a feasible
      approach to biomarker analysis and the EGF61A>G polymorphism may influence the
      effect of first-line XELOX. Consequently, this marker deserves further
      investigation.

PMID- 19850636
TI  - When do we need central nervous system prophylaxis in patients with extranodal
      NK/T-cell lymphoma, nasal type?
AB  - BACKGROUND: The incidence and risk factors of central nervous system (CNS)
      invasion is still unclear in extranodal natural killer (NK)/T-cell lymphoma,
      nasal type. PATIENTS AND METHODS: We analyzed 208 patients to study the clinical
      features and outcomes of CNS disease in extranodal NK/T-cell lymphoma. RESULTS:
      Twelve patients (5.76%, 12/208) experienced CNS disease during treatment or
      follow-up period (median 11.62 months, range 0.2-123.2 months). The clinical
      variables associated with CNS disease were Ann Arbor stage III/IV (15.87%, P
      <0.001), regional lymph node involvement (10.41%, P = 0.006), group III/IV of
      NK/T-cell lymphoma prognostic index (NKPI; 10.20%, P = 0.003), high/high
      intermediate international prognostic index (9.30%, P = 0.072) and extra-upper
      aerodigestive primary sites (9.75%, P = 0.008). In multivariate analysis, NKPI
      retained the strongest statistical power to predict CNS disease (P = 0.007,
      relative risk 9.289, 95% confidence interval 1.828-47.212) in extranodal NK/T
      cell lymphoma. CONCLUSIONS: Despite extranodal NK/T-cell lymphoma frequently
      involves paranasal sinus, a routine CNS evaluation and prophylaxis do not seem to
      be necessary in NKPI group I or II patients due to a very low incidence.
      Nevertheless, CNS prophylaxis should be considered in NKPI groups III and IV.

PMID- 19850637
TI  - Incidence of brain metastases in renal cell carcinoma treated with sorafenib.
AB  - BACKGROUND: This retrospective study evaluated the incidence of brain metastases
      in a subgroup of patients with metastatic renal cell carcinoma (RCC) who were
      randomly assigned to receive sorafenib, an oral multikinase inhibitor (400 mg
      b.i.d.), versus placebo in the phase III Treatment Approaches in Renal Cancer
      Global Evaluation Trial (TARGET). PATIENTS AND METHODS: Patients enrolled in
      TARGET at two centres (Institut Gustave Roussy, Villejuif, France, n = 85;
      Central Clinical Hospital of Military Medical Academy, Warsaw, Poland, n = 54)
      made up the current subgroup, who were retrospectively evaluated for the
      incidence of brain metastases during follow-up. The association between treatment
      (sorafenib versus placebo) and occurrence of brain metastases was evaluated by
      univariate analysis. RESULTS: The overall incidence of brain metastases in
      patients receiving sorafenib was 3% (2 of 70 patients) compared with 12% (8 of 69
      patients) in patients receiving placebo (P < 0.05). The incidence of brain
      metastases was also significantly lower in the sorafenib group after 1 (P =
      0.0447) and 2 years (P = 0.005) of treatment compared with the placebo group.
      CONCLUSIONS: In this subpopulation, sorafenib may reduce the occurrence of brain
      metastases. Antiangiogenic therapy, such as sorafenib, could be an effective
      preventive therapy for brain metastases in advanced RCC.

PMID- 19850638
TI  - Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK
      cell leukemia and extranodal NK cell lymphoma, nasal type.
AB  - BACKGROUND: Patients with natural killer (NK) cell neoplasms, aggressive NK cell
      leukemia (ANKL) and extranodal NK cell lymphoma, nasal type (ENKL), have poor
      outcome. Both diseases show a spectrum and the boundary of them remains unclear.
      The purpose of this study is to draw a prognostic model of total NK cell
      neoplasms. PATIENTS AND METHODS: We retrospectively analyzed 172 patients (22
      with ANKL and 150 with ENKL). The ENKLs consisted of 123 nasal and 27 extranasal
      (16 cutaneous, 9 hepatosplenic, 1 intestinal and 1 nodal) lymphomas. RESULTS:
      Complete remission rate for ENKL was 73% in stage I, but 15% in stage IV, which
      was consistent with that for ANKL (18%). The prognosis of ENKL was better than
      that of ANKL (median survival 10 versus 1.9 months, P < 0.0001) but was
      comparable when restricted to stage IV cases (4.0 months, P = 0.16). Multivariate
      analysis showed that four factors (non-nasal type, stage, performance status and
      numbers of extranodal involvement) were significant prognostic factors. Using
      these four variables, an NK prognostic index was successfully constructed. Four
      year overall survival of patients with zero, one, two and three or four adverse
      factors were 55%, 33%, 15% and 6%, respectively. CONCLUSION: The current
      prognostic model successfully stratified patients with NK cell neoplasms with
      different outcomes.

PMID- 19850639
TI  - Single circulating tumor cell detection and overall survival in nonmetastatic
      breast cancer.
AB  - BACKGROUND: Circulation of cancer cells in the blood is a mandatory step for
      metastasis, but circulating tumor cells (CTC) have a low metastatic efficiency in
      preclinical animal models. In this prospective study, we reported the clinical
      outcome of nonmetastatic breast cancer patients according to CTC detection.
      PATIENTS AND METHODS: In 115 nonmetastatic patients diagnosed with large operable
      or locally advanced breast cancer, we prospectively detected CTC using the
      CellSearch system before and after neoadjuvant chemotherapy in a phase II trial
      (REMAGUS02). RESULTS: At baseline, 23% of patients were CTC positive, but only
      10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC
      detection before chemotherapy was an independent prognostic factor for both
      distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95%
      confidence interval (CI) 1.4-17] and overall survival (OS; P = 0.007, RR = 9, 95%
      CI 1.8-45). CTC detection after chemotherapy was of less significance (P = 0.07
      and 0.09, respectively). Moreover, CTC detection showed interesting
      characteristics as an individual predictive test for metastatic relapses
      (sensibility 55%, specificity 81%, and global accuracy 77%). CONCLUSIONS:
      Detection of > or =1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately
      predict OS. Our findings may change the clinical management of nonmetastatic
      breast cancer and indicate that the metastatic efficiency of CTC could be higher
      than previously reported.

PMID- 19850640
TI  - High dose intensity doxorubicin in aggressive non-Hodgkin's lymphoma: a
      literature-based meta-analysis.
AB  - BACKGROUND: Aggressive non-Hodgkin's lymphoma (NHL) represents approximately 60%
      of lymphomas in the West and even more in the developing world. cyclophosphamide,
      doxorubicin, vincristine and prednisone (CHOP) is recognized as the standard
      chemotherapy regimen and the addition of rituximab to B-cell subtypes has been
      shown to significantly improve treatment outcomes. Nevertheless, still a
      significant fraction of patients is not offered rituximab due to economic
      reasons. Thus, CHOP is still offered to these patients as well as those with T
      cell subtypes. Data from the early 1990s have indicated that the dose intensity
      (DI) of doxorubicin is a key factor in predicting survival. METHODS: A Medline
      and Cochrane library search was carried out using the search terms 'CHOP',
      'lymphoma' and 'randomized trials'. Eligible trials had CHOP as a control arm and
      any regimen administering doxorubicin at a higher DI (16.6 mg/m(2)/week) as the
      investigational arm. Pooling of data was carried out using the mixed effect
      model. RESULTS: Eight trials were eligible. Patients receiving DI doxorubicin
      based regimens had a significantly better overall survival [summary hazard ratio
      (SHR) 0.82; 95% confidence interval (CI) 0.71-0.96], event-free survival (SHR
      0.86; 95% CI 0.75-0.99) and higher complete response rate (summary odds ratio
      0.91; 95% CI 0.67-0.97). CONCLUSION: High DI doxorubicin based should be
      considered in patients with aggressive NHL.

PMID- 19850641
TI  - Components of the metabolic syndrome in 500 adult long-term survivors of
      childhood cancer.
AB  - BACKGROUND: Adult survivors of childhood cancer have been reported to have an
      increased risk of late sequels. A cluster of abnormalities that contribute to the
      metabolic syndrome may be expressed at a higher level and therefore result in an
      increased risk for diabetes mellitus and cardiovascular diseases. PATIENTS AND
      METHODS: We investigated a single-centre cohort of 500 adult survivors (228
      females) of childhood cancer, median age 28 years (range 18-59 years) and median
      follow-up time 19 years (range 6-49 years). We measured total cholesterol, high
      density lipoprotein-cholesterol, systolic and diastolic blood pressure, body mass
      index and the prevalence of diabetes mellitus. Data from the epidemiological
      Monitoring van Risicofactoren en Gezondheid in Nederland (MORGEN) study were used
      to calculate standard deviation scores as normative values. RESULTS: The criteria
      of the metabolic syndrome were met in 13% of the total cohort. Acute
      lymphoblastic leukaemia (ALL) survivors treated with cranial irradiation had an
      increased risk of developing the metabolic syndrome compared with ALL survivors
      not treated with cranial irradiation (23% versus 7%, P = 0.011), probably
      determined by higher prevalence of overweight and hypertension. CONCLUSION: Adult
      survivors of childhood cancer, especially those treated with cranial irradiation,
      are at increased risk of developing the metabolic syndrome.

PMID- 19850642
TI  - Decreasing incidence of gastric MALT lymphomas in the era of anti-Helicobacter
      pylori interventions: results from a population-based study on extranodal
      marginal zone lymphomas.
AB  - BACKGROUND: Few studies have been carried out to date that have addressed the
      epidemiology of extranodal marginal zone lymphomas (EN-MZLs). PATIENTS AND
      METHODS: We carried out a population-based study to investigate incidence rates
      (IRs) and time trends of EN-MZL diagnosed in the province of Modena (Italy) from
      1997 to 2007. RESULTS: One hundred and sixty-five cases were identified from the
      Modena Cancer Registry that corresponded to an age-standardized IR of 2.3 cases
      per 100 000. A bimodal distribution of age was shown with the group of young
      patients mostly represented by males with cutaneous lymphoma. No time trends were
      observed for the IR; the incidence of gastric mucosa-associated lymphoid tissue
      (g-MALT) lymphomas (N = 51) markedly declined during the study period, dropping
      from 1.4 in 1997 to 0.2 in 2002 and then remaining stable until 2007; the
      calculated annual percent change for g-MALT was -17.0% (95% confidence interval 
      26.6% to -6.2%). We also observed a significant decrease in the rate of g-MALT
      associated with Helicobacter pylori (HP) infection from 61% to 17% of patients
      diagnosed before and after 2002 (P = 0.007; P for trend = 0.016). CONCLUSION:
      This population-based study provides new insights into recent changes in the
      epidemiology of EN-MZL, mainly represented by the sharp reduced incidence of HP
      positive g-MALT lymphomas.

PMID- 19850643
TI  - Nuclear factor-kappa B pathway and response in a phase II trial of bortezomib and
      docetaxel in patients with recurrent and/or metastatic head and neck squamous
      cell carcinoma.
AB  - BACKGROUND: Our previous study has shown that nuclear factor-kappa B (NF-kappaB)
      signaling pathway was associated with a higher rate of recurrence in head and
      neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-kappaB
      inhibitor by inhibition of proteasomes, plus docetaxel was assessed for efficacy
      and toxicity. MATERIALS AND METHODS: Patients with recurrent and/or metastatic
      HNSCC were enrolled on a phase II bortezomib/docetaxel trial (bortezomib 1.6
      mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of a 21-day cycle). Response was
      assessed using RECIST. Tissue specimens were evaluated for the presence of human
      papillomavirus (HPV) and expression of NF-kappaB-associated genes. RESULTS:
      Twenty-one of 25 enrolled patients were assessable for response; one partial
      response (PR, 5%), 10 stable disease (SD, 48%) and 10 progressive disease (PD,
      48%). Patients with PR/SD had significantly longer survival compared with
      patients with PD and the regimen was well tolerated. Only one of 20 tumors was
      positive for HPV. Patients with PD had higher expression of NF-kappaB and
      epidermal growth factor receptor-associated genes in their tumors by gene
      expression analysis. CONCLUSION: Further understanding of treatment resistance
      and interactions between bortezomib and docetaxel may provide novel approaches in
      managing HNSCC.

PMID- 19850644
TI  - Characterization of peroxisome proliferator-activated receptor alpha--independent
      effects of PPARalpha activators in the rodent liver: di-(2-ethylhexyl) phthalate
      also activates the constitutive-activated receptor.
AB  - Peroxisome proliferator chemicals (PPC) are thought to mediate their effects in
      rodents on hepatocyte growth and liver cancer through the nuclear receptor
      peroxisome proliferator-activated receptor (PPAR) alpha. Recent studies indicate
      that the plasticizer di-(2-ethylhexyl) phthalate (DEHP) increased the incidence
      of liver tumors in PPARalpha-null mice. We hypothesized that some PPC, including
      DEHP, induce transcriptional changes independent of PPARalpha but dependent on
      other nuclear receptors, including the constitutive-activated receptor (CAR) that
      mediates phenobarbital (PB) effects on hepatocyte growth and liver tumor
      induction. To determine the potential role of CAR in mediating effects of PPC, a
      meta-analysis was performed on transcript profiles from published studies in
      which rats and mice were exposed to PPC and compared the profiles to those
      produced by exposure to PB. Valproic acid, clofibrate, and DEHP in rat liver and
      DEHP in mouse liver induced genes, including Cyp2b family members that are known
      to be regulated by CAR. Examination of transcript changes by Affymetrix ST 1.0
      arrays and reverse transcription-PCR in the livers of DEHP-treated wild-type,
      PPARalpha-null, and CAR-null mice demonstrated that (1) most (approximately 94%)
      of the transcriptional changes induced by DEHP were PPARalpha-dependent, (2) many
      PPARalpha-independent genes overlapped with those regulated by PB, (3) induction
      of genes Cyp2b10, Cyp3a11, and metallothionine-1 by DEHP was CAR dependent but
      PPARalpha-independent, and (4) induction of a number of genes (Cyp8b1, Gstm4, and
      Gstm7) was independent of both CAR and PPARalpha. Our results indicate that
      exposure to PPARalpha activators including DEHP leads to activation of multiple
      nuclear receptors in the rodent liver.

PMID- 19850645
TI  - Rosiglitazone activation of PPARgamma suppresses fractalkine signaling.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      is a key transcriptional regulator of both lipid metabolism and inflammation. The
      importance of PPARgamma is accentuated by the widespread use of synthetic
      PPARgamma agonists, thiazolidinediones (such as rosiglitazone), as drugs for
      insulin resistance and type II diabetes. Fractalkine (FKN) and FKN receptor (FR)
      play an important role in the immune responses by regulating leukocyte migration
      and adhesion to inflamed peripheral tissues. In this study, we have identified a
      novel link between PPARgamma activation and FKN signaling. On one hand, the
      activation of PPARgamma by rosiglitazone in macrophages not only represses the
      transcription of the FR gene, but also prevents the plasma membrane translocation
      of the FR protein. On the other hand, the activation of PPARgamma by
      rosiglitazone in endothelial cells also impedes the nuclear export of FKN.
      Together, these data suggest that PPARgamma activation represses FKN signaling.
      These findings indicate a previously unrecognized mechanism that may contribute
      to the anti-inflammatory effect of PPARgamma.

PMID- 19850646
TI  - Epidermal growth factor and hepatocyte growth factor cooperate to enhance cell
      proliferation, scatter, and invasion in murine mammary epithelial cells.
AB  - The development of the mammary gland requires an integrated response to specific
      growth factors and steroid hormones. Hepatocyte growth factor (HGF) and its
      tyrosine kinase receptor, MET, are expressed and temporally regulated during
      mammary development and differentiation. Epidermal growth factor receptor (EGFR)
      and its ligands have also been implicated in mammary gland growth and
      morphogenesis. Since both cytokines seem to exert a morphogenic program in this
      tissue, we have investigated the possible concerted action of EGF and HGF on the
      HC11 cell line, a widely used model of nontumorigenic mammary cells. Western blot
      analysis indicated that HC11 expressed MET and EGFR, and showed ERK1/2 and AKT
      activation following HGF or EGF treatment. Analysis by real-time PCR and western
      blot showed that after an EGF but not HGF or insulin-like growth factor-I
      treatment, HC11 mammary cells exhibited an increase in MET expression at both the
      mRNA and protein levels, which was dependent on the AKT pathway. Simultaneous
      treatment with HGF and EGF increased proliferation, scatter, and invasion as
      assessed by cell count, cell cycle, scatter, and transwell assays. AKT inhibition
      did not influence the cooperation on proliferation or invasion after HGF+EGF
      treatment, while ERK1/2 inhibition abolished MET/EGFR cooperation on
      proliferation. HGF+EGF treatment increased the duration of ERK1/2 and AKT
      activation compared to HGF or EGF alone. All these data indicate that a crosstalk
      between the EGF and HGF pathways in mammary epithelial cells may modulate the
      development of the mammary gland.

PMID- 19850647
TI  - The "Silver Code" and the frail elder in the emergency department.

PMID- 19850648
TI  - Reduction of amiodarone pulmonary toxicity in patients treated with angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers.
AB  - BACKGROUND: Amiodarone (AM) is a widely used anti-arrhythmic medication. Its
      utility is, however, limited by adverse side effects. The mechanism of amiodarone
      induced toxicity (APT) in the lungs is attributed primarily to stimulation of the
      angiotensin enzyme system leading to lung cell apoptosis and cell death. This
      mechanism has been demonstrated by in vitro and in vivo experimental animal
      studies. To date, however, no in vivo human studies have confirmed this mechanism
      for APT. PURPOSE: This study was undertaken to determine whether angiotensin
      converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) offer
      a protective effect against APT in humans. Demonstration of a protective effect
      of an ACE-I or ARB would suggest that stimulation of the angiotensin enzyme
      system may be a key process in APT. DESIGN: An 8-year retrospective analysis of
      all patients on AM therapy at the James H. Quillen Veterans Affairs Medical
      Center was undertaken. RESULTS: A total of 1000 patients on AM were identified.
      One-hundred-and-seventeen were excluded from the study. Five-hundred-and-twenty
      four patients were simultaneously on an ACE-I or ARB. The remaining 359 patients
      were not. Pulmonary toxicity attributed to AM was identified in five and 14
      patients with and without concomitant ACE-I or ARB therapy, respectively. The APT
      rate for the entire patient sample was 2.2%. APT occurred in 1% of patients on an
      ACE-I or ARB and in 3.9% of patients not taking an ACE-I or ARB. This observed
      difference in percentage of APT was statistically significant. CONCLUSION: The
      concomitant use of ACE-I or ARB in patients taking AM appears to offer a
      protective effect against APT. This observation suggests that the stimulation of
      the angiotensin enzyme system may play an important role in APT in humans.

PMID- 19850649
TI  - Predictive validity of common mental disorders screening questionnaire as a
      screening instrument in long term sickness absence.
AB  - AIMS: Screening instruments for detection of common mental disorders have not
      been validity tested in long term sickness absence (LSA), which is the aim of
      this study for the Common Mental Disorders Screening Questionnaire (CMD-SQ).
      METHODS: Of all 2,414 incident persons on continuous sick-leave for more than
      eight weeks in a Danish population of 120,000 inhabitants 1,121 participated in a
      two-phased study by being screened for mental disorders by CMD-SQ in Phase 1. A
      subgroup of 337 was examined by a psychiatrist and diagnosed with Present State
      Examination in Phase 2. Results performed on Phase 2 were weighted up to Phase 1.
      Test performance was analyzed by ROC-analyses, and the fraction with a positive
      screening test, Q, the sensitivity SE, and 1 minus the specificity, SP, were
      plotted against decreasing cut-point in the tested scales for specific diagnostic
      groups. RESULTS: A sub-scale in CMD-SQ, SCL-8AD, compiled of SCL-ANX4, SCL-8, and
      SCL-DEP6, showed the best psychometric properties in detection of any mental
      disorder (AUC 0.80). Other scales were tested as well. The psychometric
      properties were dependent on sex and age. The plots of Q, SE, and 1-SP against
      decreasing cut-point gave a comprehensive view of the performance of the scales,
      which could be of significance in addressing the ethical aspects of screening.
      CONCLUSIONS: SCL-8AD is a promising candidate for the screening of mental
      disorders in LSA. It is intended to be administered by the social services
      because in Denmark there is not a legal requirement that sick-listed persons are
      certified as sick by a physician.

PMID- 19850650
TI  - Healthcare reform in Denmark.
AB  - The article discusses and describes how healthcare reform from 2007 in Denmark
      has influenced the health sector. This reform has been labelled the most radical
      reform of the political administrative system since the first democratic
      constitution in 1849. Local government reform is the latest step in a process of
      reforming the welfare state and the health sector. In more concrete terms this
      article analyzes two key issues that have had top priority in the first period of
      reform implementation - the new planning of hospital structure and the first
      generation of health agreements.

PMID- 19850651
TI  - Sick building syndrome in relation to domestic exposure in Sweden--a cohort study
      from 1991 to 2001.
AB  - BACKGROUND: Most studies on sick building syndrome (SBS) are cross-sectional and
      have dealt with symptoms among office workers. There are very few longitudinal
      cohort studies and few studies on SBS in relation to domestic exposures. The aim
      of this study was to investigate changes in SBS symptoms during the follow-up
      period and also to investigate changes in different types of indoor exposures at
      home and relate them to SBS symptoms in a population sample of adults from
      Sweden. We also wanted to investigate if there was any seasonal or regional
      variation in associations between exposure and SBS. METHODS: A random sample of
      1,000 people of the general population in Sweden (1991) was sent a self
      administered questionnaire. A follow-up questionnaire was sent in 2001. RESULTS:
      An increased risk for onset of any skin symptoms (risk ratio (RR) 2.32, 1.37
      3.93), mucosal symptoms (RR 3.17, 1.69-5.95) or general symptoms (RR 2.18, 1.29
      3.70) was found for those who had dampness or moulds in the dwelling during
      follow-up. In addition people living in damp dwellings had a lower remission of
      general symptoms and skin symptoms. CONCLUSIONS: Dampness in the dwelling is a
      risk factor for new onset of SBS symptoms. Focus on indoor environment
      improvements in dwellings can be beneficial both for the inhabitants and the
      general population. Reducing dampness in buildings is an important factor for
      reducing SBS symptoms in the general population.

PMID- 19850652
TI  - Practices and representations of health education among primary school teachers.
AB  - AIMS: School is one of the key settings for health education (HE). The objectives
      of this study are to assess primary school teachers' self-reported teaching
      practices in HE and to describe their representation concerning their role in HE.
      METHODS: A quantitative study was conducted on a sample of primary school
      teachers (n = 626) in two French regions in order to analyze their practices and
      representations in HE. A hierarchical clustering dendogram was performed on
      questions exploring representations of HE. Multiple linear regression analysis
      helped explain the motivation and self-perceived competency score. RESULTS: Three
      quarters of the teachers declare they work in HE. Only one third of them declare
      they work in a comprehensive HE perspective. The HE approach is often considered
      in terms of specific unique curriculum intervention. Two thirds of the teachers
      say they work alone in HE, the other third associate other partners and choose
      mainly school health services. Parents are rarely (12%) involved in HE
      initiatives. It is essentially the practice of HE, teacher training and teachers'
      representation of HE that condition their motivation to develop HE. CONCLUSIONS:
      Teachers can take different approaches to HE. Teachers' representation of HE
      plays an important role in the development of HE activities: some teachers
      consider that HE is the mission of the health professionals and the parents. Our
      expectations of teacher involvement should be realistic, should take into account
      the representations of their role, the difficulties they encounter, and should be
      sustained by specific training.

PMID- 19850653
TI  - Diallyl sulfide inhibits murine WEHI-3 leukemia cells in BALB/c mice in vitro and
      in vivo.
AB  - It is well documented that enhanced garlic (Allium sativum) consumption leads to
      decrease in the cancer incidences. Diallyl sulfide (DAS), one of the components
      of garlic, induces cytotoxicity and apoptosis in many cancer cell lines. The
      present studies are focused on the in vivo effects of DAS on leukemia WEHI-3
      cells in the BALB/c mice. We examined the effects of DAS on the cytotoxicity of
      WEHI-3 cells and results indicated that DAS decreased the percentage of viable
      WEHI-3 cells and these effects are dose-dependent. We examined the effects of DAS
      on WEHI-3 in vivo and the results indicated that DAS decreased the percentage of
      Mac-3 and CD11b, indicating that the differentiation of the precursor of
      macrophage cells was inhibited. DAS stimulated the percentage of CD3 and CD19,
      indicating that the differentiation of the precursor of T and B cells promoted.
      The weights of liver and spleen indicated that DAS decreased the weight of these
      organs after being compared to the control groups. One of the major
      characteristic of WEHI-3 leukemia is the enlarged spleen in murine after
      intraperitoneal (i.p.) injection of WEHI-3 cells. In conclusion, DAS affects WEHI
      3 cells both in vitro and in vivo.

PMID- 19850654
TI  - An atropine and glycopyrrolate combination reduces mortality in organophosphate
      poisoning.
AB  - Anticholinergics are the mainstay of the pharmacological management of
      organophosphate poisoning (OPP). Atropine has the potential to cause central
      toxicity which may complicate the management of this life-threatening condition.
      A combination of atropine and glycopyrrolate in equivalent dosages titrated to
      the peripheral muscarinic signs, theoretically reduces the central effect of the
      anticholinergics by 50% and thereby the risk of central toxicity, while it
      provides effective control of the peripheral manifestations of OPP. This study
      reports the clinical morbidity and mortality associated with the management of OP
      with this anticholinergic combination over a 4-year period, 2003 to 2006, at
      Tygerberg Academic Hospital (TAH). Two of the 53 patients treated for OPP died,
      with this mortality lower than that previously reported at TAH. Atropine toxicity
      was evident in 12 (22.5%) patients and responded to a temporary cessation of the
      combination infusion. The demographic profile, presenting symptoms, duration of
      stay and complications encountered were similar to previous reports from TAH.
      Patients treated with the infusion of a combination of atropine and
      glycopyrrolate had a lower mortality rate compared with earlier reports from the
      same unit, but the occurrence of atropine toxicity was unchanged despite the
      hypothesized theoretical advantage.

PMID- 19850655
TI  - Limbic encephalitis associated with systemic lupus erythematosus.
AB  - A 34-year-old woman with systemic lupus erythematosus (SLE) presented with
      general fatigue, seizures and memory loss. Magnetic resonance imaging of the
      brain showed a high signal area in the mesial temporal lobe bilaterally. Computed
      tomography scan of the chest and abdomen and ultrasound of pelvis detected no
      malignancy and tumour marker, antibodies to antineuronal antibodies (anti-Hu,
      anti-Ta and anti-Ma) and antibodies to voltage-gated potassium channels were all
      negative. The present case is limbic encephalitis (LE) associated with SLE and
      the pathogenesis may include autoimmunity shared. Our experience indicates that
      the immunologic spectrum of LE will expand to include additional immune
      mechanisms.

PMID- 19850656
TI  - The lupus susceptibility locus Sle3 is not sufficient to accelerate
      atherosclerosis in lupus-susceptible low density lipoprotein receptor-deficient
      mice.
AB  - Cardiovascular disease risk is increased in individuals suffering from systemic
      lupus erythematosus. Understanding the mechanism(s) of systemic lupus
      erythematosus-accelerated atherosclerosis is critical for the development of
      effective therapies. Our laboratory previously demonstrated that radiation
      chimeras of systemic lupus erythematosus-susceptible B6.Sle1.2.3 and low density
      lipoprotein receptor (LDLr)(-/-) mice have augmented atherosclerosis, which is
      associated with increased T-cell burden and activation in the lesion. The goals
      of this study were to further define specific immune mechanisms that mediate
      accelerated atherosclerosis and to determine whether the gene interval Sle3,
      which is linked to lupus-associated T-cell dysregulation, was sufficient to
      modulate atherogenesis. We transferred B6.Sle3 or C57Bl/6-derived bone marrow
      cells into lethally irradiated LDLr( -/-) mice (hereafter referred to as
      LDLr.Sle3 and LDLr.B6, respectively). Sixteen weeks after transplantation, the
      mice were placed on a western-type diet for 8 weeks. Our analyses revealed that
      LDLr.Sle3 mice had increased auto-antibody production against double-stranded DNA
      and cardiolipin compared with LDLr.B6 controls. We also found an increase in
      atherosclerosis-associated oxLDL antibodies. Antibody isotypes and serum cytokine
      analysis suggested that the humoral immune response in LDLr.Sle3 mice was skewed
      toward a Th2 phenotype. This finding is consistent with lupus-associated immune
      dysregulation. Additionally, LDLr.Sle3 mice had decreased serum cholesterol and
      triglyceride levels. However, there was no difference in lesion area or cellular
      composition of lesions between the two groups. These data demonstrate that,
      despite no change in lesion area, transfer of Sle3-associated T-cell
      dysregulation alone to LDLr-deficient mice is sufficient to decrease serum
      cholesterol and to exacerbate humoral immune responses that are frequently
      associated with atherosclerosis.

PMID- 19850657
TI  - An analysis of joint replacement in patients with systemic lupus erythematosus.
AB  - A small but important group of patients in our lupus cohort has needed total
      joint replacement (TJR). Arthritis was identified in 94% of our lupus patients.
      We have determined how many of our patients needed TJR, explored the risk factors
      for this procedure in patients with SLE and reviewed the outcome for these
      patients. Records of the cohort of patients with SLE who have attended our lupus
      clinic at University College of London Hospital/Middlesex from 1978 to 2008 were
      reviewed and patients who underwent TJR were identified. We recorded demographic
      data, other major systemic manifestations of SLE, autoantibody profile, previous
      use of steroids, other major systemic illnesses, smoking and alcohol habits.
      Nineteen patients with SLE from our cohort of 500 were found to have at least one
      TJR. Avascular necrosis (AVN) or concomitant rheumatoid arthritis (RA) was
      present in the majority of these patients. In contrast, age at disease onset, the
      presence of anti-cardiolipin antibodies, Raynaud's phenomenon and smoking habits
      were not found to be contributing factors for the need to replace joints. Four of
      our 19 patients (21.1%) had complications of the joint replacement: two of them
      had infections of the replaced joint, one had a large haematoma immediately after
      the surgery requiring surgical evacuation and the other had a deep vein
      thrombosis. None of the patients so far has required joint re-replacement. In
      conclusion, 4% of SLE patients in our cohort have one or more joints replaced,
      the majority because of AVN or RA.

PMID- 19850659
TI  - Abnormal expression pattern of histone demethylases in CD4(+) T cells of MRL/lpr
      lupus-like mice.

PMID- 19850658
TI  - Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a
      large multi-ethnic U.S. cohort (LXIX).
AB  - To determine the factors associated with peripheral vascular damage in systemic
      lupus erythematosus patients and its impact on survival from Lupus in Minorities,
      Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular
      damage was defined by the Systemic Lupus International Collaborating Clinics
      Damage Index (SDI). Factors associated with peripheral vascular damage were
      examined by univariable and multi-variable logistic regression models and its
      impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637
      patients (90% women, mean [SD] age 36.5 [12.6] [16-87] years) developed
      peripheral vascular damage. Age and the SDI (without peripheral vascular damage)
      were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval
      [CI] 1.01-1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09-1.56; P = 0.0043,
      respectively) in multi-variable analyses. Azathioprine, warfarin and statins were
      also statistically significant, and glucocorticoid use was borderline
      statistically significant (OR = 1.03, 95% CI 0.10-1.06; P = 0.0975). In the
      survival analysis, peripheral vascular damage was independently associated with a
      diminished survival (hazard ratio = 2.36; 95% CI 1.07-5.19; P = 0.0334). In
      short, age was independently associated with peripheral vascular damage, but so
      was the presence of damage in other organs (ocular, neuropsychiatric, renal,
      cardiovascular, pulmonary, musculoskeletal and integument) and some medications
      (probably reflecting more severe disease). Peripheral vascular damage also
      negatively affected survival.

PMID- 19850660
TI  - Vulvar intraepithelial neoplasia in a young woman with systemic lupus
      erythematosus: a case report.
AB  - Diagnosing vulvar intraepithelial neoplasia in a young woman presenting mainly
      with skin manifestations of lupus and with no other risk factors is a major
      challenge. The case of a 27-year-old woman with systemic lupus erythematosus and
      vulvar intraepithelial neoplasia is described. Although progression of vulvar
      intraepithelial neoplasia to invasive planocellular carcinoma is rare, prompt and
      adequate diagnosis and treatment will help ensure the best possible quality of
      life.

PMID- 19850661
TI  - Interleukin-6 release from peripheral mononuclear cells is associated to disease
      activity and treatment response in patients with lupus nephritis.

PMID- 19850662
TI  - Prognostic factors in patients with systemic lupus erythematosus admitted to the
      intensive care unit.
AB  - The objectives of this study were to identify risk factors associated with
      mortality in patients with systemic lupus erythematosus (SLE) admitted to the
      intensive care unit (ICU) and to evaluate the usefulness of Acute Physiologic and
      Chronic Health Evaluation (APACHE) II score to predict outcomes in these
      patients, through the use of a retrospective patient record review from a
      multidisciplinary intensive care unit in a teaching hospital. One hundred and
      four patients with SLE admitted to the ICU were included in the study. The mean
      age of patients was 32.44 years, 96.2% were female and 61.5% were admitted with
      infection. The mean APACHE II score was 19.7, 46.2% had acute renal dysfunction,
      67.3% received inotropics/ vasopressors, 27.9% pulmonary artery catheter and 74%
      invasive mechanical ventilation. The mean length of stay in ICU was 18.5 days and
      mortality rate was 32.7%. In the univariate logistic regression analysis, factors
      associated with mortality were high APACHE II score, use of
      inotropics/vasopressors, pulmonary artery catheter and invasive mechanical
      ventilation. High APACHE II score and use of inotropics/vasopressors remained
      significant in the multi-variate analysis. The area under the receiver operating
      characteristic curve of the APACHE II score to predict mortality was 0.689 (95%
      CI 0.586-0.791 p = 0.002) and the Hosmer- Lemeshow chi( 2) was 5.094 (p = 0.747).
      We conclude that the mortality rate in patients with SLE admitted to the ICU is
      high. The most common cause of admission was infection. The factors associated
      with mortality were high APACHE II score and the use of inotropics/vasopressors.
      APACHE II score was unable to accurately predict mortality.

PMID- 19850663
TI  - Gigantomastia in a patient with systemic lupus erythematosus successfully treated
      by reduction mammoplasty.
AB  - The objective of the study was to describe a Filipino woman with systemic lupus
      erythematosus (SLE) who developed gigantomastia associated with
      hyperoestrogenemia and successfully treated by reduction mammoplasty. A 37-year
      old Filipino woman with SLE of 5-year duration presented with enlargement of
      breasts, which became more noticeable and progressive during disease flares
      requiring increased steroid dose (+ or - 40 mg/day). Following control of the
      last SLE flare, with prednisone effectively tapered to 15 mg/day, she consented
      to surgical breast reduction. Preoperative physical examination recorded the
      right and left breast measurement of 61 cm and 54.5 cm from sternal notch to
      nipple tip, respectively. serum oestrogen assay was elevated. She successfully
      underwent reduction mammoplasty with free nipple graft, with an uneventful
      postoperative course. The breast tissue oestrogen and progesterone receptor
      assays were strongly positive. In the succeeding months, SLE disease remained
      stable with prednisone tapered to 10 mg daily. This case illustrates a rare
      occurrence of gigantomastia associated with hyperoestrogenemia in a patient with
      SLE, successfully treated with reduction mammoplasty.

PMID- 19850664
TI  - Contracting for health and curative care use in Afghanistan between 2004 and
      2005.
AB  - Afghanistan has used several approaches to contracting as part of its national
      strategy to increase access to basic health services. This study compares changes
      in the utilization of outpatient curative services from 2004 to 2005 between the
      different approaches for contracting-out services to non-governmental service
      providers, contracting-in technical assistance at public sector facilities, and
      public sector facilities that did not use contracting. We find that both
      contracting-in and contracting-out approaches are associated with substantial
      double difference increases in service use from 2004 to 2005 compared with non
      contracted facilities. The double difference increase in contracting-out
      facilities for outpatient visits is 29% (P < 0.01), while outpatient visits from
      female patients increased 41% (P < 0.01), use by the poorest quintile increased
      68% (P < 0.01) and use by children aged under 5 years increased 27% (P < 0.05).
      Comparing the individual contracting-out approaches, we find similar increases in
      outpatient visits when contracts are managed directly by the Ministry of Public
      Health compared with when contracts are managed by an experienced international
      non-profit organization. Finally, contracting-in facilities show even larger
      increases in all the measures of utilization other than visits from children
      under 5. Although there are minor differences in the results between contracting
      out approaches, these differences cannot be attributed to a specific contracting
      out approach because of factors limiting the comparability of the groups. It is
      nonetheless clear that the government was able to manage contracts effectively
      despite early concerns about their lack of experience, and that contracting has
      helped to improve utilization of basic health services.

PMID- 19850665
TI  - Neural mechanisms for learned birdsong.
AB  - Learning by imitation is essential for transmitting many aspects of human
      culture, including speech, language, art, and music. How the human brain enables
      imitation remains a mystery, but the underlying neural mechanisms must harness
      sensory feedback to adaptively modify performance in reference to the object of
      imitation. Although examples of imitative learning in nonhuman animals are
      relatively rare, juvenile songbirds learn to sing by copying the song of an adult
      tutor. The delineation of neural circuits for birdsong raises the promise that
      this complex form of vocal learning, which bears strong parallels to human speech
      learning, can be understood in terms of underlying neural mechanisms. This
      promise is now being more fully realized, with recent experimental advances
      leading to better understanding of the central motor codes for song and the
      central mechanisms by which auditory experience modifies song motor commands to
      enable vocal learning.

PMID- 19850666
TI  - Parsing storage from retrieval in experimentally induced amnesia.

PMID- 19850668
TI  - Is arson the crime most strongly associated with psychosis?--A national case
      control study of arson risk in schizophrenia and other psychoses.
AB  - BACKGROUND: The association of psychosis with certain serious crimes, such as
      homicide, has been clearly demonstrated, but it is uncertain to what extent
      psychotic disorders are associated with arson. METHODS: We used a case-control
      design to investigate the association of being diagnosed with schizophrenia and
      other psychoses and committing arson. Data were obtained from Swedish national
      registers for criminal convictions, hospital discharge diagnoses (International
      Classification of Diseases, Ninth Revision [ICD-9], and International
      Classification of Diseases, Tenth Revision [ICD-10]), and sociodemographic
      factors for 1988-2000. We included all convicted arson offenders of both sexes in
      Sweden (N=1689) and compared them with a random sample of general population
      control subjects (N=40,560). RESULTS: After adjustment for sociodemographic
      confounders, arson offenders were more likely to be diagnosed with schizophrenia
      (in men, adjusted odds ratio [OR]=22.6, 95% confidence interval [CI]=14.8-34.4;
      in women, adjusted OR=38.7, 95% CI=20.4-73.5) or other psychoses (in men,
      adjusted OR=17.4, 95% CI=11.1-27.5; in women, adjusted OR=30.8, 95% CI=18.8
      50.6). CONCLUSIONS: Individuals with schizophrenia and other psychoses have
      significantly increased risks of an arson conviction. These risk estimates are
      higher than those reported for other violent crimes and place arson in the same
      category as homicide as crimes that are most strongly associated with psychotic
      disorders.

PMID- 19850670
TI  - 48 years on: is the suicide act fit for purpose?

PMID- 19850669
TI  - Social anhedonia and schizotypy in a community sample: the Maryland longitudinal
      study of schizotypy.
AB  - Social anhedonia has been employed in psychometric high-risk studies to identify
      putative schizotypes. To date, this research has focused almost exclusively on
      college samples. The current study sought to examine the validity of social
      anhedonia as an indicator of risk for schizophrenia-spectrum disorders within a
      community sample. Furthermore, we evaluated the role of other individual
      difference variables in accounting for variable clinical severity within the
      social anhedonia group including trait affectivity, social support, and family
      environment. Following the mailed questionnaire screening of 2434 eighteen-year
      olds, laboratory assessments were conducted with individuals identified as being
      high in social anhedonia (n=86) and a comparison sample (n=89). Compared with the
      control group, individuals in the social anhedonia group were found to have
      higher rates of mood disorders, elevated schizophrenia-spectrum personality
      disorder characteristics, greater negative symptom characteristics, and lower
      global functioning. Individuals within the social anhedonia group also reported
      greater trait negative affectivity, lower positive affectivity, less social
      support, and more family conflict. Low social support and problematic family
      environment were found to be related to elevations in spectrum personality
      disorder characteristics and poorer functioning within the social anhedonia
      group. These cross-sectional findings from a community sample provide further
      support for social anhedonia as a possible indicator of schizotypy.

PMID- 19850671
TI  - Property: the future of human tissue?

PMID- 19850672
TI  - Comparison of the drug-drug interactions potential of erlotinib and gefitinib via
      inhibition of UDP-glucuronosyltransferases.
AB  - We aimed to investigate and compare the effects of erlotinib and gefitinib on UDP
      glucuronosyltransferase (UGT) activities and to quantitatively evaluate their
      drug-drug interaction (DDI) potential due to UGT inhibition. The inhibitory
      effects of erlotinib and gefitinib on UGTs were determined using high-performance
      liquid chromatography by measuring the formation rates for 4-methylumbelliferone
      (4-MU) glucuronide, imipramine N-glucuronide, and bilirubin glucuronides using
      recombinant human UGT isoforms and human liver microsomes (HLMs) in the absence
      or presence of erlotinib and gefitinib. Inhibition kinetic studies were
      conducted. Area under the curve (AUC) ratios were used to predict the risk of
      potential DDI in vivo. Erlotinib exhibited selective potent competitive
      inhibition against 4-MU glucuronidation by UGT1A1, and gefitinib demonstrated a
      wide range of inhibition against UGT-mediated 4-MU glucuronidation, particularly
      against UGT1A1, UGT1A7, UGT1A9, and UGT2B7. Erlotinib also exerted potent mixed
      inhibition against bilirubin glucuronidation in HLMs. We estimated that
      coadministration of erlotinib at 100 mg/day or higher doses may result in at
      least a 30% increase in the AUC of drugs predominantly cleared by UGT1A1. Thus,
      the coadministration of erlotinib with drugs primarily cleared by UGT1A1 may
      result in potential DDI. In contrast, gefitinib is unlikely to cause a clinically
      significant DDI through inhibition of glucuronidation.

PMID- 19850673
TI  - Impact of molecular processing in the hinge region of therapeutic IgG4 antibodies
      on disposition profiles in cynomolgus monkeys.
AB  - The IgG4 isotype antibody is a potential candidate for immunotherapy when reduced
      effector functions are desirable. However, antigen binding fragment (Fab) arm
      exchange leads to functional monovalency with potentially reduced therapeutic
      efficacy. Mutagenesis studies suggested that the CH3 domain and not the core
      hinge is dominantly involved in in vivo molecular processing. This work
      investigated whether stabilization of the core hinge of a therapeutic IgG4
      antibody by mutation of Ser228 to Pro (S228P) would be sufficient to prevent in
      vivo Fab arm exchange. In vitro experiments evaluated the influence of different
      levels of oxidation-reduction conditions in buffer and serum on Fab arm exchange
      (swapping) of wild-type (WT) IgG4 and IgG1 and of IgG4 S228P, which included a
      sterically neutral second mutation (Leu235 replaced by Glu). The objective of
      single-dose pharmacokinetic experiments in cynomolgus monkeys was to determine
      whether the mutation reduced IgG4 swapping in vivo. The results indicated that
      S228P mutation did not completely prevent Fab arm exchange in vitro in buffer
      under reducing conditions relative to IgG4 WT. The immunoassay findings were
      confirmed by mass spectrometry measurements. Results of the in vivo studies
      suggested that the therapeutic IgG4 WT antibody exchanged Fab arms with
      endogenous cynomolgus monkey IgG4, resulting in bispecific IgG4 antibodies with
      monovalency for the therapeutic target. In contrast, serum from cynomolgus
      monkeys dosed with the IgG4 mutant was virtually free of swapped IgG4. In
      conclusion, the results indicated that IgG4 swapping in vivo was markedly
      attenuated by S228P mutation.

PMID- 19850674
TI  - Substrate specificity of microbial transglutaminase as revealed by three
      dimensional docking simulation and mutagenesis.
AB  - Transglutaminases (TGases) are used in fields such as food and pharmaceuticals.
      Unlike other TGases, microbial transglutaminase (MTG) activity is Ca(2+)
      independent, broadening its application. Here, a three-dimensional docking model
      of MTG binding to a peptide substrate, CBZ-Gln-Gly, was simulated. The data
      reveal CBZ-Gln-Gly to be stretched along the MTG active site cleft with
      hydrophobic and/or aromatic residues interacting directly with the substrate.
      Moreover, an oxyanion binding site for TGase activity may be constructed from the
      amide groups of Cys64 and/or Val65. Alanine mutagenesis verified the simulated
      binding region and indicated that large molecules can be widely recognized on the
      MTG cleft.

PMID- 19850675
TI  - Shear flow promotes amyloid-{beta} fibrilization.
AB  - The rate of formation of amyloid fibrils in an aqueous solution of amyloid-beta
      (Abeta) is greatly increased when the solution is sheared. When Abeta solution is
      stirred with a magnetic stirrer bar at 37 degrees C, a rapid increase in
      thioflavin T fluorescence is observed. Atomic Force Microscopy (AFM) images show
      the formation of aggregates, the growth of fibrils and the intertwining of the
      fibrils with time. Circular dichroism (CD) spectroscopy of samples taken after
      stirring shows a transition from random coil to alpha-helix to beta-sheet
      secondary structure over 20 h at 37 degrees C. The fluorescence, AFM and CD
      measurements are all consistent with the formation of amyloid fibrils. Quiescent,
      non-stirred solutions incubated at 37 degrees C showed no evidence of amyloid
      formation over a period of 3 days. Couette flow was found to accelerate the
      formation of amyloid fibrils demonstrating that the primary effect of stirring is
      not mixing but shearing. Only very small shear forces are applied to individual
      molecules in our experiments. Simple calculation suggests that the force is too
      small to support a hypothesis that shearing promotes partial unfolding of the
      protein as is observed.

PMID- 19850676
TI  - Engineering of a novel hybrid enzyme: an anti-inflammatory drug target with
      triple catalytic activities directly converting arachidonic acid into the
      inflammatory prostaglandin E2.
AB  - Cyclooxygenase isoform-2 (COX-2) and microsomal prostaglandin E(2) synthase-1
      (mPGES-1) are inducible enzymes that become up-regulated in inflammation and some
      cancers. It has been demonstrated that their coupling reaction of converting
      arachidonic acid (AA) into prostaglandin (PG) E(2) (PGE(2)) is responsible for
      inflammation and cancers. Understanding their coupling reactions at the molecular
      and cellular levels is a key step toward uncovering the pathological processes in
      inflammation. In this paper, we describe a structure-based enzyme engineering
      which produced a novel hybrid enzyme that mimics the coupling reactions of the
      inducible COX-2 and mPGES-1 in the native ER membrane. Based on the hypothesized
      membrane topologies and structures, the C-terminus of COX-2 was linked to the N
      terminus of mPGES-1 through a transmembrane linker to form a hybrid enzyme, COX-2
      10aa-mPGES-1. The engineered hybrid enzyme expressed in HEK293 cells exhibited
      strong triple-catalytic functions in the continuous conversion of AA into PGG(2)
      (catalytic-step 1), PGH(2) (catalytic-step 2) and PGE(2) (catalytic-step 3), a
      pro-inflammatory mediator. In addition, the hybrid enzyme was also able to
      directly convert dihomo-gamma-linolenic acid (DGLA) into PGG(1), PGH(1) and then
      PGE(1) (an anti-inflammatory mediator). The hybrid enzyme retained similar K(d)
      and V(max) values to that of the parent enzymes, suggesting that the
      configuration between COX-2 and mPGES-1 (through the transmembrane domain) could
      mimic the native conformation and membrane topologies of COX-2 and mPGES-1 in the
      cells. The results indicated that the quick coupling reaction between the native
      COX-2 and mPGES-1 (in converting AA into PGE(2)) occurred in a way so that both
      enzymes are localized near each other in a face-to-face orientation, where the
      COX-2 C-terminus faces the mPGES-1 N-terminus in the ER membrane. The COX-2-10aa
      mPGES-1 hybrid enzyme engineering may be a novel approach in creating
      inflammation cell and animal models, which are particularly valuable targets for
      the next generation of NSAID screening.

PMID- 19850677
TI  - Superficial groundwater contamination by artificial radionuclides by the nuclear
      site of Saluggia (Vercelli, Italy): radiological monitoring activities.
AB  - During the last 15 y, by the Saluggia (Vercelli, Italy) nuclear site, episodes of
      contamination of the superficial groundwater happened due to artificial
      radionuclides. The local network of radiological monitoring around the nuclear
      site, managed by Arpa Piemonte from the late 1980s, highlighted the presence of
      (60)Co, (90)Sr, (137)Cs and (3)H during this period. The object of this paper was
      to give particular evidence not to analytical aspects, but to the methodical
      approach used to solve the problems that arose. In fact, the intrinsic hydro
      geological vulnerability of the zone, the typology and conditions of the plants
      (all very old) and the presence of the 'Acquedotto del Monferrato' tap water well
      field, one of the most important in Piemonte, at approximately 2 km downstream of
      the site, made the situation very difficult to approach.

PMID- 19850678
TI  - The exon 3-deleted growth hormone receptor is associated with better response to
      pegvisomant therapy in acromegaly.
AB  - CONTEXT: The deletion of exon 3 in the GH receptor (GHR) has been associated with
      a different biochemical picture and response to therapy in acromegaly. OBJECTIVE:
      The aim of the study was to determine whether or not the GHR genotype influences
      the efficacy of pegvisomant treatment. DESIGN AND SETTING: A cross-sectional
      study was conducted in six Spanish university hospitals. PATIENTS: Forty-four
      acromegalic patients with active disease and resistance to somatostatin analogs
      participated in the study. RESULTS: The prevalence of the full-length GHR and the
      exon 3-deleted GHR homozygous and heterozygous genotypes was 41, 2, and 57%,
      respectively. There were no differences in IGF-I or GH pre-pegvisomant levels
      related to GHR genotype. The exon 3-deleted patients required approximately 20%
      lower doses of pegvisomant per kilogram of weight (28 +/- 11 compared to 22 +/- 7
      mg per kg of weight; P = 0.033) to normalize IGF-I. A stepwise multivariate
      linear regression analysis (R(2) = 0.27; P = 0.003) identified male gender (beta
      = -0.79; P = 0.03) and d3-GHR genotype (beta = -0.64; P = 0.007) as the only
      significant predictors of the dose of pegvisomant per kilogram of weight. In
      addition, d3-GHR carriers required fewer months for IGF-I normalization (P <
      0.01). A stepwise multivariate linear regression analysis (R(2) = 0.40; P =
      0.001) revealed that the only significant predictor of the time to IGF-I
      normalization was the dose of pegvisomant per kilogram of weight (beta = 0.451; P
      = 0.001). CONCLUSIONS: The exon 3 deletion in the GHR predicts an improved
      response to pegvisomant therapy in acromegaly.

PMID- 19850679
TI  - Concomitant medication use can confound interpretation of the combined
      dexamethasone-corticotropin releasing hormone test in Cushing's syndrome.
AB  - CONTEXT: The ability of combined dexamethasone-corticotropin releasing hormone
      (Dex-CRH) testing to distinguish pseudo-Cushing's syndrome (PCS) from Cushing's
      syndrome is controversial. One factor potentially impairing diagnostic efficacy
      is the concomitant use of commonly prescribed medications that may alter
      dexamethasone metabolism. OBJECTIVE: Our objective was to assess the diagnostic
      accuracy of the Dex-CRH test and evaluate the potential impact of concomitant
      drugs. DESIGN: The study was a retrospective one. PARTICIPANTS: Participants
      included 101 patients [60 Cushing's disease (CD); 41 PCS] who underwent 112 Dex
      CRH tests. Patients were divided into two groups, depending on use of medications
      potentially interfering with dexamethasone metabolism: 58 tests were classified
      as No Meds (32 CD; 26 PCS) and 54 as Meds (34 CD; 20 PCS). The latter group was
      further subdivided into patients taking one medication vs. those taking multiple
      medications. MAIN OUTCOME MEASURES: Diagnostic accuracy of different serum
      cortisol and ACTH thresholds at baseline and 15 min after CRH injection was
      assessed. RESULTS: The specificity of a baseline post-low-dose-dexamethasone
      suppressed test cortisol lower than 1.4 microg/dl (38 nmol/liter) was
      significantly higher in the No Meds vs. the Meds group (P = 0.014). Sensitivity
      and specificity using a post-CRH cortisol cutoff of 1.4 microg/dl (38 nmol/liter)
      were 93.1% (95% confidence interval = 88.4-97.8) and 92.3% (95% confidence
      interval = 87-97.6) in the No Meds group. The specificity of a cortisol lower
      than 1.4 microg/dl (38 nmol/l) at 15 min after CRH was significantly higher in
      patients taking only one medication vs. those on multidrug treatment (P < 0.05).
      CONCLUSIONS: Medications commonly prescribed in hypercortisolemic patients
      undergoing Dex-CRH testing may contribute to the variable diagnostic accuracy of
      this test. Prospective studies to address this issue are needed.

PMID- 19850680
TI  - Programmed death ligand 1 (PD-L1) gene variants contribute to autoimmune
      Addison's disease and Graves' disease susceptibility.
AB  - CONTEXT: Despite much investigation, a substantial amount of the genetic
      susceptibility to autoimmune diseases remains unaccounted for. Recently, a single
      nucleotide polymorphism (SNP) in the programmed death ligand 1 (PD-L1) gene has
      been associated with Graves' disease (GD) in a Japanese patient cohort. Our aim
      was to determine whether variants in PD-L1 are also associated with autoimmune
      Addison's disease (AAD) and to replicate the previous association in patients
      with GD from the United Kingdom. DESIGN AND PATIENTS: We analyzed eight SNPs
      within PD-L1 in a United Kingdom cohort of 315 AAD subjects and 316 healthy
      controls. We then replicated our experiment in a cohort of 342 Norwegian AAD
      cases and 379 controls and in 496 United Kingdom GD subjects. RESULTS: Three of
      the eight SNPs studied, part of a haplotype block in the PD-L1 gene, showed
      modest association with both AAD and GD in the United Kingdom cohort, with
      maximum evidence at the marker RS1411262 [United Kingdom AAD odds ratio 1.33 (5
      95% confidence interval 1.02-1.73), P(genotype) = 0.028; GD odds ratio 1.36 (5
      95% confidence interval 1.07-1.72), P(genotype) = 0.033]. Association with
      genotypes at the same three markers was confirmed in the Norwegian AAD cohort
      [P(genotype) = 0.011-0.020]. A recessive effect at the most associated alleles
      was observed in both the AAD and GD cohorts. CONCLUSIONS: We confirm the role of
      PD-L1 variants in GD susceptibility and extend these findings to demonstrate
      association in two Northern European patient cohorts with AAD. PD-L1 joins the
      growing number of known susceptibility loci exerting modest effects in these
      autoimmune disorders.

PMID- 19850681
TI  - Association of KCNQ1 polymorphisms with the gestational diabetes mellitus in
      Korean women.
AB  - CONTEXT: Similar genetic factors may play role in the pathogenesis of gestational
      diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). However, genetic
      studies on GDM are relatively scarce as compared with T2DM. OBJECTIVE: A recent
      genome-wide association (GWA) study has proved that three KCNQ1 polymorphisms
      were significantly associated with the risk of T2DM in various ethnic groups.
      This study aimed to examine possible genetic effects of these KCNQ1 polymorphisms
      on the risk of GDM. DESIGN: Three KCNQ1 polymorphisms (rs2074196, rs2237892, and
      rs2237895) were genotyped using TaqMan assay. The genotype distributions between
      GDM patients and normal controls were analyzed using logistic regression models.
      In addition, GDM-related phenotypes were analyzed using multiple regression
      models. SETTING: All GDM patients recruited from Cheil General Hospital in Seoul,
      Korea, between 2003 and 2008. PARTICIPANTS: PARTICIPANTS included 930 Korean
      females with GDM and the data of healthy controls from the previous GWA study.
      RESULTS: KCNQ1 polymorphisms of rs2237892 and rs2237895 were significantly
      associated with the risk of GDM (P = 0.003 and 0.005, respectively). In the
      analyses of the GDM-related phenotype, only the risk allele of KCNQ1 rs2237895
      was significantly associated with a high-level insulin sensitivity oral glucose
      tolerance test among patients with GDM (P = 0.0003, 0.004, and 0.05 for
      codominant, dominant, and recessive models, respectively). CONCLUSION: KCNQ1
      polymorphisms shown to be associated with increased risk for T2DM in the recent
      GWA study might also represent genetic factors contributing to the development of
      GDM in Koreans.

PMID- 19850682
TI  - The effect of transdermal testosterone on mammographic density in postmenopausal
      women not receiving systemic estrogen therapy.
AB  - CONTEXT: Greater mammographic density is associated with increased breast cancer
      risk and reduced diagnostic mammographic sensitivity and may be seen with
      estrogen/progestin therapy (EPT). The effects of testosterone therapy on
      mammographic density in postmenopausal women not on EPT are not known. OBJECTIVE:
      Our objective was to compare effects of two doses of the testosterone transdermal
      patch (TTP) with placebo in postmenopausal women without concomitant EPT on
      mammographic density over 52 wk. DESIGN: We conducted a randomized, double-blind,
      placebo-controlled, parallel-group, multinational trial. PATIENTS: Patients
      included 279 postmenopausal women participating in a testosterone and sexual
      function study with paired mammograms for baseline and 52 wk/exit. INTERVENTIONS:
      Patients were randomized to placebo, TTP 150 microg/d, or TTP 300 microg/d,
      stratified by menopause type (natural or surgical). MAIN OUTCOME MEASURES: Change
      from baseline to wk 52 in the percentage of dense tissue (PD) on digital
      mammograms. RESULTS: A total of 250 women with paired mammograms for study
      baseline and wk 52 were included in the primary analysis. Mean age was 54.6 yr,
      baseline body mass index was 27.5 kg/m(2), and 78% were naturally menopausal.
      There were no baseline differences between groups. Mean changes from baseline (+/
      SEM) in PD for placebo, TTP 150 microg/d and TTP 300 microg/d were small (0.05 +/
      0.16, 0.06 +/- 0.19, and 0.21 +/- 0.17%) and not significantly different. There
      were no statistically significant differences from placebo for total dense or
      nondense area and no significant relationships between hormone levels and PD
      after adjustment for body mass index. CONCLUSION: TTP therapy over 52 wk appears
      to have no significant effect on digitally quantified absolute or percent dense
      mammographic area in postmenopausal women not using EPT.

PMID- 19850683
TI  - Hepcidin in obese children as a potential mediator of the association between
      obesity and iron deficiency.
AB  - CONTEXT: Obesity and iron deficiency are two of the most common nutritional
      disorders worldwide. Several studies found higher rates of iron deficiency in
      obese than in normal-weight children. Hepcidin represents the main inhibitor of
      intestinal iron absorption, and its expression is increased in adipose tissue of
      obese patients. Leptin is able, in vitro, to raise hepcidin expression.
      OBJECTIVES: Aims of this work were 1) to assess the association between poor iron
      status and obesity, 2) to investigate whether iron homeostasis of obese children
      may be modulated by serum hepcidin variations, and 3) to assess the potential
      correlation between leptin and serum hepcidin variations. METHODS: Iron status
      and absorption as well as hepcidin, leptin, and IL-6 levels were studied in 60
      obese children and in 50 controls. RESULTS: Obese children showed lower iron and
      transferrin saturation (both P < 0.05) and higher hepcidin levels (P = 0.004)
      compared with controls. A direct correlation between hepcidin and obesity degree
      (P = 0.0015), and inverse correlations between hepcidin and iron (P = 0.04),
      hepcidin and transferrin saturation (P = 0.005), and hepcidin and iron absorption
      (P = 0.003) were observed. A correlation between leptin and hepcidin (P = 0.006)
      has been found. The correlation remained significant when adjusted for body mass
      index, sex, pubertal stage, and IL-6 values. CONCLUSIONS: We propose that in
      obese patients, increased hepcidin production, at least partly leptin mediated,
      represents the missing link between obesity and disrupted iron metabolism.

PMID- 19850685
TI  - Impact of type 1 diabetes and insulin treatment on plasma levels and fractional
      synthesis rate of retinol-binding protein 4.
AB  - CONTEXT: Retinol binding protein 4 (RBP4) levels are elevated in insulin
      resistant states and reduced in type 1 diabetes (T1D), but it is unknown whether
      changes in insulin levels and glycemic control alter RBP4 levels. In vivo
      synthesis rates of RBP4 and their relationship to RBP4 levels remain to be
      determined. OBJECTIVE: The aim of the study was to determine whether the
      synthesis rate of RBP4 is altered in people with T1D during both insulin
      deficiency and insulin treatment. DESIGN: Seven T1D participants were studied on
      two occasions, during 8 h of insulin deprivation and during insulin treatment,
      and compared with nondiabetic (ND) controls. MAIN OUTCOME MEASURES: We measured
      in vivo fractional synthesis rate of RBP4 using [ring-(13)C(6)]phenylalanine as a
      tracer and RBP4 concentration in plasma by nephelometric assay and Western blot
      analyses. RESULTS: Plasma RBP4 levels were lower (P < 0.01) in insulin-treated
      T1D than in ND but were not different between insulin-deprived T1D and ND
      participants. Synthesis rates of RBP4 in ND (2.46 +/- 0.29%/h) were higher than
      in insulin-treated T1D (1.45 +/- 0.21) (P = 0.02), but there was no difference
      between ND and insulin-deprived T1D (2.24 +/- 0.24). Glucose levels were not
      different between ND and insulin-treated T1D, but insulin levels were higher in
      insulin-treated T1D (82.8 +/- 2 pmol/liter) than in ND (28.7 +/- 6) and insulin
      deprived T1D (4.6 +/- 1.6) (P < 0.01). CONCLUSIONS: Insulin treatment that
      achieved normoglycemia but relative hyperinsulinemia was associated with lower
      RBP4 synthesis and levels in T1D. Short-term insulin deprivation and
      hyperglycemia had no effect on RBP4 levels and synthesis rates in T1D.

PMID- 19850686
TI  - Synchronization of adolescent blood pressure and pubertal somatic growth.
AB  - BACKGROUND: Blood pressure (BP) and growth increase at an accelerated rate during
      puberty. The temporal relationship of the two events has not been well
      characterized. OBJECTIVE: The purpose of this current investigation was to
      examine the rate of BP change in relation to pubertal growth with the intent to
      shed light on new mechanisms by which BP is regulated. METHODS: We examined data
      from a cohort of 182 normotensive children who had measurements made semiannually
      for up to 12 yr. From the recorded heights, we identified the subject-specific
      pubertal growth spurt (PGS) using a growth curve model. With the estimated PGS as
      an anchoring point, we obtained the rates at which BP and weight changed as
      continuous functions of time for the duration of pubertal growth. Examining BP on
      a scale relative to PGS placed BP development in the context of pubertal growth.
      RESULTS: Average ages at PGS were 11.5 for girls and 13.3 for boys. Fitted spline
      models estimated that at the time of PGS, the mean systolic BP was 100 mm Hg for
      girls and 107 mm Hg for boys; the mean diastolic BP at the PGS was 59 mm Hg for
      girls and 61 mm Hg for boys. The most intriguing observation was that rate of
      change in systolic BP and weight peaked at precisely the estimated PGS.
      CONCLUSION: The time synchronization of rates of change in BP, weight, and height
      suggests common regulating mechanisms for somatic growth and BP or growth changes
      that secondarily affect BP.

PMID- 19850684
TI  - Effects of conjugated equine estrogens on cognition and affect in postmenopausal
      women with prior hysterectomy.
AB  - CONTEXT: Different menopausal hormone therapies may have varied effects on
      specific cognitive functions. We previously reported that conjugated equine
      estrogens (CEE) with medroxyprogesterone acetate had a negative impact on verbal
      memory but tended to impact figural memory positively over time in older
      postmenopausal women. OBJECTIVE: The objective of the study was to determine the
      effects of unopposed CEE on changes in domain-specific cognitive function and
      affect in older postmenopausal women with prior hysterectomy. DESIGN: This was a
      randomized, double blind, placebo-controlled clinical trial. SETTING: The study
      was conducted at 14 of 40 Women's Health Initiative (WHI) clinical centers.
      PARTICIPANTS: Participants were 886 postmenopausal women with prior hysterectomy,
      aged 65 yr and older (mean 74 yr), free of probable dementia, and enrolled in the
      WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of 3 yr and followed
      up for a mean of 2.70 yr. INTERVENTION: Intervention was 0.625 mg of CEE daily or
      placebo. MAIN OUTCOME MEASURES: Annual rates of change in specific cognitive
      functions and affect, adjusted for time since randomization, were measured.
      RESULTS: Compared with placebo, unopposed CEE was associated with lower spatial
      rotational ability (P < 0.01) at initial assessment (after 3 yr of treatment), a
      difference that diminished over 2.7 yr of continued treatment. CEE did not
      significantly influence change in other cognitive functions and affect.
      CONCLUSIONS: CEE did not improve cognitive functioning in postmenopausal women
      with prior hysterectomy. CEE was associated with lower spatial rotational
      performance after an average of 3 yr of treatment. Overall, CEE does not appear
      to have enduring effects on rates of domain-specific cognitive change in older
      postmenopausal women.

PMID- 19850687
TI  - Effect of growth hormone therapy on severe short stature and skeletal deformities
      in a patient with combined Turner syndrome and Langer mesomelic dysplasia.
AB  - BACKGROUND: Homozygous mutation of the short stature homeobox-containing gene,
      SHOX, results in Langer mesomelic dysplasia (LMD). Our case presented with severe
      short stature and skeletal deformities with Turner syndrome (TS) and a SHOX gene
      abnormality due to a downstream allele deletion in her normal X chromosome.
      Medical literature review did not reveal similar cases that were treated with GH
      therapy. METHOD: We present an 11-yr-old with combined TS and LMD with severe
      short stature and skeletal deformities. She was studied for the effect of GH
      therapy on stature and skeletal deformities. Karyotype testing showed
      45,X/46,X,idic(X). Genetic analysis of SHOX gene testing did not detect any
      exonic mutations. Interestingly, both alleles of the flanking marker DXYS233, a
      marker downstream of the 3' end of SHOX coding sequence, were absent with
      resultant LMD. GH therapy in the mean dose of 0.321 mg/kg/wk was administered for
      4 yr (0.287, 0.355, 0.317, and 0.327 mg/kg/week in the first, second, third, and
      fourth years, respectively). Clinical data were reviewed. RESULT: The growth
      rates of 3.46, 3.87, 2.3, and 0.7 cm/yr were observed in the first, second,
      third, and fourth years of the GH therapy, respectively. There was no clinical
      deterioration of the skeletal deformities. CONCLUSION: There was a failure to
      achieve growth improvements with GH therapy for 4 years, but there was no
      worsening of the skeletal deformities. We conclude that GH therapy may not be
      beneficial in severe short stature due to combined TS and LMD resulting from
      homozygous SHOX deficiency.

PMID- 19850688
TI  - Self-reported sleep duration and sleep disturbance are independently associated
      with cortisol secretion in the Whitehall II study.
AB  - CONTEXT: The association of short sleep duration with cortisol secretion has not
      been thoroughly examined in large community dwelling populations and the relative
      importance of short sleep duration and sleep disturbance is unclear. OBJECTIVE:
      The objective of the study was to assess the relationships between self-reported
      sleep duration, sleep disturbance, and salivary cortisol secretion. DESIGN: This
      was a cross-sectional analysis using data from phase 7 (2002-2004) of the
      Whitehall II study. Sleep disturbances were assessed using a modified version of
      the Jenkins Scale. SETTING: The occupational cohort was originally recruited in
      1985-1989. PARTICIPANTS: Analyses included 2751 participants with complete
      cortisol measures and who collected their first sample within 15 min of waking,
      were not on medication affecting cortisol secretion, and had complete information
      for all covariates. OUTCOME MEASURE: Six saliva samples were taken on waking,
      waking + 0.5, 2.5, 8, and 12 h and bedtime for the assessment of the cortisol
      awakening response and the slope in cortisol secretion across the day. RESULTS:
      In mutually adjusted analyses, both sleep duration and disturbances were
      independently associated with a flatter diurnal slope in cortisol secretion, such
      that evening cortisol secretion was raised in those reporting short sleep
      duration and high sleep disturbance. Short sleep duration was also associated
      with the cortisol awakening response. These effects were independent of a number
      of covariates, including waking time on day of sampling and stress on the day of
      cortisol assessment. CONCLUSION: Short sleep duration and increased sleep
      disturbances are independently associated with diurnal slope in cortisol
      secretion of a large community-based cohort of middle-aged men and women.

PMID- 19850689
TI  - Mutant BRAF(T1799A) can be detected in the blood of papillary thyroid carcinoma
      patients and correlates with disease status.
AB  - CONTEXT: The BRAF(T1799A) transversion is the most frequent morphotype-specific
      somatic mutation in papillary thyroid carcinoma (PTC). The ability to detect this
      mutation in the circulation could aid in diagnosis and follow-up of PTC patients.
      OBJECTIVE: Our objective was to develop and clinically validate a sensitive and
      specific assay for the detection of BRAF(T1799A) in blood samples from PTC
      patients. DESIGN: We developed an allele-specific real-time PCR method for the
      detection of BRAF(T1799A) in blood samples and studied prospectively blood
      samples from 193 patients with thyroid cancer (173 PTC, 20 non-PTC) attending for
      routine follow-up. The results of molecular testing were correlated with disease
      status and thyroglobulin measurements. BRAF(T1799A) status of the original tumor
      samples was also confirmed, where available. RESULTS: The assay had a detection
      sensitivity of fewer than one heterozygote BRAF(T1799A)-carrying cell per 100,000
      diploid cells, without detectable cross-reactivity between wild-type BRAF and
      BRAF(T1799A). Circulating BRAF(T1799A) was detected in 20 of 173 PTC patients and
      in none of the 20 non-PTC patients. BRAF(T1799A)-positive samples contained
      between one in 326 and fewer than one in 100,000 copies of BRAF(T1799A). Tissue
      BRAF status correlated with blood BRAF status, whereas BRAF(T1799A) positivity in
      blood correlated with the presence of active disease at the time of the blood
      draw, with eight of the 38 PTC patients with persistent/recurrent disease being
      positive for circulating BRAF(T1799A) (relative risk vs. circulating BRAF(T1799A)
      negative, 2.55; P < 0.04). CONCLUSIONS: BRAF(T1799A) can be detected in the blood
      of PTC patients with residual or metastatic disease and may provide diagnostic
      information.

PMID- 19850690
TI  - Molecular mechanism for repression of 17alpha-hydroxylase expression and
      androstenedione production in granulosa cells.
AB  - CONTEXT: According to the traditional two-cell two-gonadotropin model of
      follicular steroidogenesis, androgen production arises exclusively from theca
      cells. The granulosa cells, in turn, utilize androstenedione and testosterone,
      which are aromatized into estrone and estradiol, respectively. Differential
      expression of the activator protein-1 (AP-1) transcription factor, c-fos, has
      been postulated to result in distinct patterns of steroidogenesis in the theca
      and granulosa cell compartments. We hypothesize that c-fos functions to inhibit
      the production of 17alpha-hydroxylase 17,20 lyase (CYP17) in granulosa cells,
      thereby suppressing androgen synthesis. OBJECTIVE: Our objective was to define
      the role of c-fos in the regulation of CYP17 production in granulosa cells.
      DESIGN AND METHODS: Human luteinized granulosa (HGL5) cells were utilized for all
      experiments. The following techniques were used: mRNA extraction, steroid
      quantification, small interfering RNA silencing, microarray analysis, and
      immunohistochemistry. RESULTS: Immunohistochemistry studies demonstrated
      significant staining of c-fos in the granulosa cell layer, but absent staining
      for CYP17. Conversely, the theca cell layer did not stain for c-fos, but staining
      was evident for CYP17. Treatment of HGL5 cells with the MAPK kinase inhibitor
      PD98059 resulted in an 11-fold increase in CYP17 mRNA levels. In c-fos gene
      silenced cells, CYP17 mRNA levels increased 8-fold. Androstenedione production
      was increased 13-fold after treatment with PD98059. CONCLUSIONS: These results
      suggest that the AP-1 transcription factor, c-fos, may be one of the factors
      responsible for CYP17 repression and hence suppression of androstenedione
      production in granulosa cells. This may provide an explanation for the lack of
      CYP17 in granulosa cells.

PMID- 19850692
TI  - Prevalence and functional significance of thyrotropin receptor blocking
      antibodies in children and adolescents with chronic lymphocytic thyroiditis.
AB  - CONTEXT: TSH receptor (TSHR) blocking antibodies (Abs) inhibit TSH-induced
      thyroid growth and function in some adults with chronic lymphocytic thyroiditis
      (CLT), but their role in the pediatric age range is unknown. OBJECTIVES: Our
      objectives were: 1) to determine the prevalence of TSHR blocking Abs in children
      and adolescents with CLT and 2) assess their functional significance both in vivo
      and in vitro. DESIGN AND SETTING: This was a retrospective study in a referral
      outpatient setting. PATIENTS: Sera from a total of 87 CLT patients and 33
      controls were studied. MAIN OUTCOME MEASURES: TSHR Abs were measured by both
      ELISA and bioassay. RESULTS: Eight of 87 children and adolescents with CLT
      (9.2%), including one as young as 4 yr of age, had TSHR Abs in serum as measured
      by ELISA. The prevalence was significantly higher in individuals whose serum TSH
      concentration was 20 mU/liter or greater within 3 months of study than in less
      hypothyroid patients (eight of 45 vs. none of 42, P < 0.005). Conversely, TSHR Ab
      positive patients were significantly more hypothyroid at diagnosis but only when
      the analysis was restricted to those with severe hypothyroidism was a decreased
      prevalence of goiter observed. IgG purified from TSHR Ab sera retained the TSH
      binding-inhibitory activity and TSHR Ab-positive sera inhibited TSH-induced
      stimulation of cAMP significantly more than normal. CONCLUSIONS: TSHR-blocking
      Abs contribute significantly to the severity of the hypothyroidism in some
      children with CLT, but as compared with adults, they appear to play less of a
      role in determining the presence or absence of a goiter.

PMID- 19850691
TI  - Prevention of relapse of Graves' disease by treatment with an intrathyroid
      injection of dexamethasone.
AB  - INTRODUCTION: Antithyroid drugs are widely used in the treatment of Graves'
      disease (GD), but the relapse rate is very high after therapy withdrawal. We
      evaluated the reduction effects of intrathyroid injection of dexamethasone (IID)
      on the relapse rate of hyperthyroidism in patients with newly diagnosed GD.
      PATIENTS AND METHODS: A total of 191 patients with GD completed the study. After
      6 months of treatment with methimazole (MMI), the patients were randomly assigned
      to receive either MMI (96 patients) alone or MMI combined with IID (MMI+IID; 95
      patients) treatment for 3 months, followed by continuing a dose of MMI that would
      maintain euthyroidism for the next 9 months in all of the patients. After
      withdrawal of the medical therapy, patients were followed for 24 months, and the
      relapse rate of hyperthyroidism was evaluated. RESULTS: No statistical difference
      was observed in the levels of serum FT(4), TSH, or TSH receptor antibodies (TR
      Ab), the thyroid volume, or the TR-Ab positive rate between the two groups at
      month 6. After the next 3 months of treatment with MMI+IID or MMI alone, the
      levels of TSH increased significantly, and the levels of serum TR-Ab, the TR-Ab
      positive rate, and thyroid volume decreased significantly in the MMI+IID group
      compared with the MMI group. Seven patients (7.4%) experienced a relapse of overt
      hyperthyroidism in the MMI+IID group and 49 patients (51%) in MMI group during
      the 2-yr follow-up period (P < 0.001). CONCLUSIONS: MMI+IID treatment is helpful
      to prevent relapse of hyperthyroidism in GD after medical therapy withdrawal.

PMID- 19850693
TI  - Preadipocyte factor-1 is associated with marrow adiposity and bone mineral
      density in women with anorexia nervosa.
AB  - CONTEXT: Despite having low visceral and sc fat depots, women with anorexia
      nervosa (AN) have elevated marrow fat mass, which is inversely associated with
      bone mineral density (BMD). Adipocytes and osteoblasts differentiate from a
      common progenitor cell, the human mesenchymal stem cell. Therefore, understanding
      factors that regulate this differentiation process may provide insight into bone
      loss in AN. OBJECTIVE: The objective of the study was to investigate the
      relationship between preadipocyte factor-1 (Pref-1), a member of the epidermal
      growth factor-like family of proteins and regulator of adipocyte and osteoblast
      differentiation, and fat depots and BMD in AN. DESIGN: This was a cross-sectional
      study. SETTING: The study was conducted at a clinical research center. PATIENTS:
      Patients included 20 women with AN (26.8 +/- 1.5 yr) and 10 normal-weight
      controls (29.2 +/- 1.7 yr). INTERVENTIONS: There were no interventions. MAIN
      OUTCOMES MEASURE: Pref-1, leptin, IGF-I, IGF binding protein (IGF-BP)-2 and
      estradiol levels were measured. BMD of the spine and hip was measured by dual
      energy x-ray absorptiometry. Marrow fat content of the L4 vertebra and femur was
      measured by (1)H-magnetic resonance spectroscopy. RESULTS: Pref-1 levels were
      significantly higher in AN compared with controls (P = 0.01). There was a
      positive correlation between Pref-1 and marrow fat of the proximal femoral
      metaphysis (R = 0.50, P = 0.01) and an inverse association between leptin and L4
      marrow fat (R = -0.45, P < 0.05). There was an inverse association between Pref-1
      and BMD of both the anteroposterior spine and lateral spine (R = -0.54, P =
      0.003; R = -0.44, P = 0.02, respectively). CONCLUSIONS: Pref-1 is elevated in AN.
      Pref-1, IGF-I, IGF-BP2 and leptin are associated with marrow adiposity and BMD.

PMID- 19850694
TI  - Follow-up of low-risk differentiated thyroid cancer patients who underwent
      radioiodine ablation of postsurgical thyroid remnants after either recombinant
      human thyrotropin or thyroid hormone withdrawal.
AB  - BACKGROUND: We previously demonstrated comparable thyroid remnant ablation rates
      in postoperative low-risk thyroid cancer patients prepared for administration of
      3.7GBq (131)I (100 mCi) after recombinant human (rh) TSH during T(4) (L-T4)
      therapy vs. withholding L-T4 (euthyroid vs. hypothyroid groups). We now compared
      the outcomes of these patients 3.7 yr later. PATIENTS AND METHODS: Fifty-one of
      the 63 original patients (28 euthyroid, 23 hypothyroid) participated. Forty-eight
      received rhTSH and serum thyroglobulin (Tg) sampling. A (131)I whole-body scan
      was performed in 43 patients, and successful ablation was defined by criteria
      from the previous study. Based on the criterion of uptake less than 0.1% in
      thyroid bed, 100% (43 of 43) remained ablated. When no visible uptake instead was
      used, five patients (four euthyroid, one hypothyroid) had minimal visible
      activity. When the TSH-stimulated Tg criterion was used, only two of 45 (one
      euthyroid, one hypothyroid) had a stimulated Tg level greater than 2 ng/ml.
      RESULTS: No patient in either group died, and no patient declared disease free
      had sustained tumor recurrence. Nine (four euthyroid, five hypothyroid) had
      received additional (131)I between the original and current studies due to
      detectable Tg or imaging evidence of disease; with follow-up, all now had a
      negative rhTSH-stimulated whole-body scan and seven (three euthyroid, four
      hypothyroid) had a stimulated serum Tg less than 2 ng/ml. CONCLUSIONS: In
      conclusion, after a median 3.7 yr, low-risk thyroid cancer patients prepared for
      postoperative remnant ablation either with rhTSH or after L-T4 withdrawal were
      confirmed to have had their thyroid remnants ablated and to have comparable rates
      of tumor recurrence and persistence.

PMID- 19850695
TI  - Familial correlations in postmenopausal serum concentrations of sex steroid
      hormones and other mitogens: a twins and sisters study.
AB  - BACKGROUND: Serum concentrations of some hormones are risk factors for certain
      cancers, but little is known about their familial associations especially for
      females. METHODS: We measured serum concentrations of estradiol (E(2)),
      testosterone (T), SHBG, prolactin, and IGF-I for 645 Australian female
      postmenopausal twins and their sisters [182 monozygotic (MZ) and 107 dizygotic
      (DZ) pairs and 67 nontwin sisters] using well-established immunoassays. After
      suitable transformation and adjusting for age, body mass index (BMI), and time
      since menopause, familial correlations and proportions of variance attributed to
      genetic (h(2)) and nongenetic factors common to sisterships (c(2)) were estimated
      under the classic twin multivariate normal model using FISHER. RESULTS: For all
      serum concentrations except prolactin, MZ, DZ, and sister pairs were correlated
      (P < 0.001). MZ correlations were in the range 0.5-0.7, and for all serum
      concentrations, there were no differences between DZ and sister correlations. MZ
      correlations were greater than DZ and sister correlations for log SHBG (P =
      0.0001), IGF-I (P = 0.0002), and square-root T (P = 0.007) but not log E(2) (P =
      0.3), and the respective h(2) estimates were 0.56 (SE = 0.14), 0.53 (0.17), 0.39
      (0.14), and 0.14 (0.16). For log E(2) and square-root T, c(2) estimates were 0.39
      (0.14) and 0.22 (0.12). CONCLUSION: There are strong familial correlations in
      postmenopausal SHBG, IGF-I, and to a lesser extent T, which are consistent with a
      genetic etiology. For E(2), and to a lesser extent T, correlations are consistent
      with substantial nongenetic familial factors. The latter might include maternal
      effects.

PMID- 19850696
TI  - Lack of diastolic reserve in patients with heart failure and normal ejection
      fraction.
AB  - BACKGROUND: The genesis of symptoms in patients with heart failure (HF) and
      normal ejection fraction (HFNEF) is unclear. Most investigations of HFNEF have
      focused on cardiac function at rest although most of these patients are
      breathless only on exercise. Stress-induced impairment in systolic or diastolic
      function could result in these symptoms. Method and Result- Forty-one patients
      with HFNEF and 29 controls underwent dobutamine stress echocardiography with
      color tissue Doppler imaging. Wall motion score index and regional myocardial
      systolic velocity (Sm) were measured at and peak stress. Systolic (Sa), early
      diastolic (Ea), and late diastolic (Aa) mitral annular velocities were averaged
      over the 6 periannular sites. Mitral annular long-axis velocity was lower in the
      HFNEF than controls at rest. Global, regional, and long-axis systolic function
      did not worsen with stress in the HFNEF group. The Ea decreased and the E/Ea
      increased with stress in the HFNEF but not in controls. The 6-minute walk
      distance was shorter and negatively correlated to the E/EA ratio at rest and
      stress in the HFNEF group. CONCLUSIONS: Impaired diastolic reserve results in
      stress-induced increase in the left ventricular end-diastolic pressure in
      patients with HFNEF giving rise to exercise intolerance.

PMID- 19850698
TI  - Multidimensional Prognostic Index based on a comprehensive geriatric assessment
      predicts short-term mortality in older patients with heart failure.
AB  - BACKGROUND: Multidimensional impairment of older patients may influence the
      clinical outcome of diseases. The aim of this study was to evaluate whether a
      Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric
      assessment predicts short-term mortality in older patients with heart failure.
      METHODS AND RESULTS: In this prospective study with a 1-month follow-up, 376
      patients aged 65 and older with a diagnosis of heart failure were enrolled. A
      standardized comprehensive geriatric assessment that included information on
      functional (activities of daily living and instrumental activities of daily
      living), cognitive (Short Portable Mental Status Questionnaire), and nutritional
      status (Mini Nutritional Assessment), as well as on risk of pressure sore (Exton
      Smith Scale), comorbidities (Cumulative Illness Rating Scale Index), medications,
      and social support network, was used to calculate the MPI for mortality using a
      previously validated algorithm. The New York Heart Association, the Enhanced
      Feedback for Effective Cardiac Treatment, and the Acute Decompensated Heart
      Failure National Registry regression model scores were also calculated. Higher
      MPI values were significantly associated with higher 30-day mortality, both in
      men (MPI-1, 2.8%; MPI-2, 15.3%; MPI-3, 47.4%; P=0.000) and women (MPI-1, 0%; MPI
      2, 6.5%; MPI-3, 14.6%; P=0.011). The discrimination of the MPI was also good,
      with areas under the receiver operating characteristic curves (men: 0.83; 95% CI,
      0.75 to 0.90; women: 0.80; 95% CI, 0.71 to 0.89) greater than receiver operating
      characteristic areas of New York Heart Association (men: 0.63; 95% CI, 0.57 to
      0.69; P=0.015; women: 0.65; 95% CI, 0.55 to 0.75; P=0.064), Enhanced Feedback for
      Effective Cardiac Treatment (men: 0.69; 95% CI, 0.58 to 0.79; P=0.045; women:
      0.71; 95% CI, 0.55 to 0.87; P=0.443), and Acute Decompensated Heart Failure
      National Registry scores (men: 0.65; 95% CI, 0.52 to 0.78; P=0.023; women: 0.67;
      95% CI, 0.49 to 0.83, P=0.171). CONCLUSIONS: The MPI, calculated from information
      collected in a standardized comprehensive geriatric assessment, is useful to
      estimate the risk of 1-month mortality in older patients with heart failure.

PMID- 19850699
TI  - Characteristics and clinical significance of late gadolinium enhancement by
      contrast-enhanced magnetic resonance imaging in patients with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Myocardial late gadolinium enhancement (LGE) on contrast-enhanced
      magnetic resonance imaging (CE-MRI) of patients with hypertrophic cardiomyopathy
      (HCM) has been suggested to represent intramyocardial fibrosis and, as such, an
      adverse prognostic risk factor. We evaluated the characteristics of LGE on CE-MRI
      and explored whether LGE among patients with HCM was associated with genetic
      testing, severe symptoms, ventricular arrhythmias, or sudden cardiac death (SCD).
      METHODS AND RESULTS: Four hundred twenty-four patients with HCM (age=55+/-16
      years [range 2 to 90], 41% females), without a history of septal
      ablation/myectomy, underwent CE-MRI (GE 1.5 Tesla). We evaluated the relation
      between LGE and HCM genes status, severity of symptoms, and the degree of
      ventricular ectopy on Holter ECG. Subsequent SCD and appropriate implanted
      cardioverter defibrillator (ICD) therapies were recorded during a mean follow-up
      of 43+/-14 months (range 16 to 94). Two hundred thirty-nine patients (56%) had
      LGE on CE-MRI, ranging from 0.4% to 65% of the left ventricle. Gene-positive
      patients were more likely to have LGE (P<0.001). The frequencies of New York
      Heart Association class >or=3 dyspnea and angina class >or=3 were similar in
      patients with and without LGE (125 of 239 [52%] versus 94 of 185 [51%] and 24 of
      239 [10%] versus 18 of 185 [10%], respectively, P=NS). LGE-positive patients were
      more likely to have episodes of nonsustained ventricular tachycardia (34 of 126
      [27%] versus 8 of 94 [8.5%], P<0.001), had more episodes of nonsustained
      ventricular tachycardia per patient (4.5+/-12 versus 1.1+/-0.3, P=0.04), and had
      higher frequency of ventricular extrasystoles/24 hours (700+/-2080 versus 103+/
      460, P=0.003). During follow-up, SCD occurred in 4 patients, and additional 4
      patients received appropriate ICD discharges. All 8 patients were LGE positive
      (event rate of 0.94%/y, P=0.01 versus LGE negative). Two additional heart failure
      related deaths were recorded among LGE-positive patients. Univariate associates
      of SCD or appropriate ICD discharge were positive LGE (P=0.002) and presence of
      nonsustained ventricular tachycardia (P=0.04). The association of LGE with events
      remained significant after controlling for other risk factors. CONCLUSIONS: In
      patients with HCM, presence of LGE on CE-MRI was common and more prevalent among
      gene-positive patients. LGE was not associated with severe symptoms. However, LGE
      was strongly associated with surrogates of arrhythmia and remained a significant
      associate of subsequent SCD and/or ICD discharge after controlling for other
      variables. If replicated, LGE may be considered an important risk factor for
      sudden death in patients with HCM.

PMID- 19850697
TI  - Prevalence and prognostic value of elevated urinary albumin excretion in patients
      with chronic heart failure: data from the GISSI-Heart Failure trial.
AB  - BACKGROUND: Increased urinary excretion of albumin is an early sign of kidney
      damage and a risk factor for progressive cardiovascular and renal diseases and
      heart failure. There is, however, only limited information on the prevalence and
      prognostic role of urinary albumin excretion in patients with established chronic
      heart failure. METHODS AND RESULTS: A total of 2131 patients enrolled in 76 sites
      participating in the GISSI-Heart Failure trial provided a first morning spot
      sample of urine at any of the clinical visits scheduled in the trial to calculate
      the urinary albumin-to-creatinine ratio. The relation between log-transformed
      urinary albumin-to-creatinine ratio and all-cause mortality (428 deaths, time
      from urine collection to event or censoring) was evaluated with Cox multivariable
      models adjusted for all significant risk factors at the time of urine collection,
      in the study population, and in patients without diabetes or hypertension. Almost
      75% of the patients had normal urinary albumin excretion, but 19.9% had
      microalbuminuria (30 to 299 mg/g creatinine) and 5.4% had overt albuminuria
      (>or=300 mg/g). There was a progressive, significant increase in the adjusted
      rate of mortality in the study population (hazard ratio, 1.12; 95% CI, 1.05 to
      1.18 per 1-U increase of log(urinary albumin-to-creatinine ratio), P=0.0002) and
      in the subgroup of patients without diabetes or hypertension. Randomized
      treatments (n-3 polyunsaturated fatty acids or rosuvastatin) had no major impact
      on albumin excretion. CONCLUSIONS: Independently of diabetes, hypertension, or
      renal function, elevated albumin excretion is a powerful prognostic marker in
      patients with chronic heart failure.

PMID- 19850700
TI  - Episodes of acute heart failure syndrome are associated with increased levels of
      troponin and extracellular matrix markers.
AB  - BACKGROUND: Increased myocyte loss and extracellular matrix (ECM) turnover are
      central mechanisms that contribute to pathological myocardial remodeling in
      chronic heart failure (HF). We tested the hypothesis that episodes of acute HF
      syndrome (AHFS) are associated with transient increases in markers of myocyte
      injury and ECM turnover beyond those observed in chronic stable HF. METHODS AND
      RESULTS: Markers of myocyte injury and ECM turnover were assessed in 80 patients
      prospectively divided into 3 groups: AHFS (n=39); chronic stable systolic HF
      (n=21); and control subjects without HF (n=20). Myocyte injury was assessed by
      measuring plasma troponin I. ECM turnover was assessed by measuring plasma matrix
      metalloproteinases, tissue inhibitors of matrix metalloproteinases, and
      procollagen N-terminal type I and procollagen type III N-terminal peptides. In
      the AHFS group, biomarkers were obtained (1) at the time of hospital admission
      for an episode of HF decompensation, (2) at the time of hospital discharge, and
      (3) several weeks after discharge in patients who had returned to a chronic
      stable compensated state. In patients with stable HF (versus non-HF controls),
      there was a small increase in troponin I and little or no difference in any
      marker of ECM turnover. In patients with AHFS, troponin I and 3 markers of ECM
      turnover (matrix metalloproteinases-2, tissue inhibitors of matrix
      metalloproteinases-1, and procollagen type III N-terminal peptides) were elevated
      (versus chronic stable HF), and all fell toward chronic HF levels in patients who
      returned to a compensated state. CONCLUSIONS: Episodes of AHFS are associated
      with transient increases in markers of myocyte injury and ECM turnover that may
      reflect an acceleration of pathological myocardial remodeling during AHFS.

PMID- 19850701
TI  - Employment trajectories and changes in sense of coherence.
AB  - BACKGROUND: Knowledge of the associations between labour market position and
      sense of coherence (SOC) comes mainly from cross-sectional studies. We
      investigated whether change in employment status is associated with change in SOC
      and whether such an association varies when young (<30 years) and older employees
      are compared. METHODS: Data were derived from two studies: a cohort of initially
      non-permanent employees (n = 1898) was followed up for four years, and a cohort
      representing the national workforce (n = 9623) was followed up for five years.
      Labour market position at baseline and at follow-up (permanent/fixed-term
      job/unemployed) was used to locate the participants into six or nine different
      employment trajectories depending on the cohort. SOC was measured with a 13-item
      questionnaire. Associations of the employment trajectories with changes in SOC
      were analysed with general linear models. RESULTS: In both cohorts the change of
      SOC was significantly associated with type of employment trajectory. The results
      supported the hypothesis of more favourable development of SOC among those whose
      trajectories were directed upward: the associations of poor SOC with unemployment
      are indisputable, whereas the effects of fixed-term employment seem to be neutral
      or even positive. The analysis by age revealed that the effects of employment
      trajectory on SOC are particularly strong among individuals aged below 30 years.
      CONCLUSION: This longitudinal study provided evidence for the interpretation that
      stabilisation of SOC associates with stabilisation of the labour market position.
      Moreover, the fluctuations of SOC seem to depend on the type of trajectory
      throughout adult life.

PMID- 19850702
TI  - Optimal insulin treatment in type 2 diabetes.

PMID- 19850704
TI  - DNA sequence analysis of cagA 3' motifs of Helicobacter pylori strains from
      patients with peptic ulcer diseases.
AB  - The Helicobacter pylori cagA gene is a major virulence factor that plays an
      important role in gastric pathologies. DNA sequence data for the cagA 3' region
      of Western isolates differ markedly in their EPIYA motifs from those of East
      Asian isolates. An increase in the number of these motifs is known to be
      associated with gastric cancer. Whether such an association is also the case for
      peptic ulceration was investigated in this study. Gastric biopsies were collected
      from 96 patients with duodenal ulcer (DU), gastric ulcer (GU) and gastritis. The
      types of EPIYA motif detected by PCR among 28 DU strains were 13 ABC, eight ABCC,
      six ABCCC, and in one patient both ABC and ABCCCCC; among nine GU strains were
      two ABC, five ABCC and two ABCCC; and among 40 gastritis strains were 35 ABC and
      five ABCC. DNA sequencing was carried out to confirm the detection of the EPIYA
      motif types and to analyse their peptide sequences. A significant association was
      found between the number of the EPIYA-C motifs (>or=2) and peptic ulceration
      (P=0.00001) compared with gastritis. In conclusion, this study shows that our
      patients harboured cagA-positive H. pylori strains with EPIYA motifs of the
      Western type and that the increase in the number of EPIYA-C motifs was
      significantly associated with DU and GU but not with gastritis, indicating
      predictive association with the severity of the disease.

PMID- 19850705
TI  - Clostridium sordellii lethal toxin gene is not detectable by PCR in the
      intestinal flora of infants who died from sudden infant death syndrome or other
      causes.

PMID- 19850706
TI  - Role and clinical course of verotoxigenic Escherichia coli infections in
      childhood acute diarrhoea in Argentina.
AB  - The aim of this study was to investigate the role and clinical course of
      verotoxigenic Escherichia coli (VTEC) infections in children with acute diarrhoea
      from Argentina, the country with the highest worldwide incidence of haemolytic
      uraemic syndrome (HUS). To accomplish this objective, 437 samples from children
      up to 6 years old with acute diarrhoea were collected and processed. More than 60
      % of the children studied presented watery or mucous diarrhoea without blood, and
      in 25.2 % of the cases the samples contained blood. In a first screening, a
      multiplex PCR was performed to detect the presence of the vt(1), vt(2), eae, ehxA
      and saa virulence genes. The strains were then isolated and analysed to
      characterize their serotypes, virulence genes, antibiotic susceptibility profiles
      and verotoxin (VT) production. Forty-four of the 437 samples (10.1 %) were
      positive for VTEC virulence genes. VTEC-infected patients presented different
      types of diarrhoea (27.3 % belonged to the non-bloody type). Several serotypes
      and virulence genotypes were found. Isolates belonged to the serotypes O157 : H7,
      O145 : H(-), O26 : H11, O121 : H19, O111 : H2 and O118 : H2. HUS developed in 16
      (36.4 %) patients positive for VTEC virulence genes. All of the VTEC isolates
      produced a cytopathic effect on Vero cell monolayers, confirming the ability to
      express VT. Despite most strains being sensitive to all of the antimicrobials
      studied, a positive association between clinical progression to HUS and
      antibiotic therapy was observed for the total number of patients studied, as well
      as for the VTEC(+) group. In conclusion, the data obtained in this study increase
      our knowledge of the role and clinical course of VTEC infection in childhood
      acute diarrhoea beyond bloody diarrhoea, and might be considered for the
      prevention, diagnosis and management of this disease. It is possible that the
      optimal approach for VTEC diagnosis could be using multiplex PCR to search for
      the presence of the vt(1), vt(2), eae and ehxA genes.

PMID- 19850707
TI  - Moraxella catarrhalis bacteraemia associated with prosthetic vascular graft
      infection.
AB  - Moraxella catarrhalis, formerly called Branhamella catarrhalis, 'Neisseria
      catarrhalis' or 'Micrococcus catarrhalis', is a Gram-negative, aerobic
      diplococcus frequently found as a colonizer of the upper respiratory tract. Over
      the last 20-30 years, this bacterium has emerged as a genuine pathogen, and is
      now considered an important cause of otitis media in children and an aetiological
      agent in pneumonia in adults with chronic obstructive pulmonary disease. However,
      bacteraemia due to M. catarrhalis has rarely been reported. Presented here is a
      case of M. catarrhalis bacteraemia associated with prosthetic vascular graft
      infection along with a review of the relevant literature.

PMID- 19850703
TI  - Three-year efficacy of complex insulin regimens in type 2 diabetes.
AB  - BACKGROUND: Evidence supporting the addition of specific insulin regimens to oral
      therapy in patients with type 2 diabetes mellitus is limited. METHODS: In this 3
      year open-label, multicenter trial, we evaluated 708 patients who had suboptimal
      glycated hemoglobin levels while taking metformin and sulfonylurea therapy.
      Patients were randomly assigned to receive biphasic insulin aspart twice daily,
      prandial insulin aspart three times daily, or basal insulin detemir once daily
      (twice if required). Sulfonylurea therapy was replaced by a second type of
      insulin if hyperglycemia became unacceptable during the first year of the study
      or subsequently if glycated hemoglobin levels were more than 6.5%. Outcome
      measures were glycated hemoglobin levels, the proportion of patients with a
      glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight
      gain. RESULTS: Median glycated hemoglobin levels were similar for patients
      receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based
      regimens (P=0.28). However, fewer patients had a level of 6.5% or less in the
      biphasic group (31.9%) than in the prandial group (44.7%, P=0.006) or in the
      basal group (43.2%, P=0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a
      second type of insulin (P=0.002). [corrected] Median rates of hypoglycemia per
      patient per year were lowest in the basal group (1.7), higher in the biphasic
      group (3.0), and highest in the prandial group (5.7) (P<0.001 for the overall
      comparison). The mean weight gain was higher in the prandial group than in either
      the biphasic group or the basal group. Other adverse event rates were similar in
      the three groups. CONCLUSIONS: Patients who added a basal or prandial insulin
      based regimen to oral therapy had better glycated hemoglobin control than
      patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes
      and less weight gain occurred in patients adding basal insulin. (Current
      Controlled Trials number, ISRCTN51125379.)

PMID- 19850708
TI  - Fatal spontaneous bacterial peritonitis and necrotizing fasciitis with
      bacteraemia caused by Bacillus cereus in a patient with cirrhosis.
AB  - We report a case of spontaneous bacterial peritonitis and necrotizing fasciitis
      caused by Bacillus cereus in a cirrhotic patient without preceding disruption of
      skin or symptoms of gastroenteritis. This rapidly fatal infection due to B.
      cereus adds to the long list of aetiologies of infectious complications among
      patients with cirrhosis of the liver.

PMID- 19850709
TI  - Prospective relationship between maternal depressive symptoms and asthma
      morbidity among inner-city African American children.
AB  - OBJECTIVE: To examine prospective relationships between caregiver's depressive
      symptoms and child asthma morbidity among inner-city African American families.
      METHODS: Phone surveys were conducted 6 months apart with 262 African American
      mothers of children with asthma. Cross-lagged structural path analysis was used
      for data analyses. RESULTS: Using goodness-of-fit indices, the final model for
      asthma symptoms had a good fit to the data. Time 1 (T1) maternal depressive
      symptoms predicted T2 child asthma symptoms (beta =.16, p <.01); however, T1
      asthma symptoms did not predict T2 maternal depressive symptoms (beta =.03, non
      significant). In contrast, in the final model for emergency department (ED)
      visits there was no predictive association between maternal depressive symptoms
      and ED visits. CONCLUSION: Maternal depressive symptoms may have a detrimental
      effect on child asthma morbidity among inner-city African American families,
      rather than vice versa. Ameliorating maternal depressive symptoms may result in
      better asthma outcomes for inner-city children.

PMID- 19850710
TI  - Response to the commentary: A worldwide call for multimodal inpatient treatment
      for children and adolescents suffering from chronic pain and pain-related
      disability.

PMID- 19850711
TI  - Toxocariasis: incidence, prevalence and the time serum remains positive in school
      children from Campinas, SP, Brazil.

PMID- 19850712
TI  - New models for primary care are needed for osteoarthritis.
AB  - Musculoskeletal problems are the most common cause of restriction in daily life
      in most countries. Most health care for musculoskeletal problems is provided in
      primary care settings, and back pain and joint problems together represent the
      largest workload of cases of chronic disease seen and managed there. This article
      reflects on aspects of the occurrence, natural history, prognosis, and management
      of common joint problems in primary care. Although the biomedical model has
      contributed to major advances, a model that embraces chronic pain management and
      its psychological and social components is needed. In particular, primary care is
      the ideal arena to achieve high-impact secondary prevention of pain and
      disability in people with osteoarthritis. Physical therapists are in a crucial
      position in primary care to provide support for self-management of this
      condition, especially for interventions related to exercise and behavioral
      change.

PMID- 19850713
TI  - There is inadequate evidence to determine the effectiveness of nonpharmacological
      and nonsurgical interventions for hand osteoarthritis: an overview of high
      quality systematic reviews.
AB  - BACKGROUND: Patients with hand osteoarthritis are commonly treated by health care
      professionals (allied to medicine). Practice should be informed by updated
      evidence from systematic reviews of randomized controlled trials. PURPOSE: The
      purpose of this overview is to summarize the evidence from systematic reviews of
      the effectiveness of nonpharmacological and nonsurgical interventions for
      patients with hand osteoarthritis. DATA SOURCES AND STUDY SELECTION: Systematic
      reviews published between January 2000 and October 2008 were identified by a
      comprehensive literature search. DATA EXTRACTION AND SYNTHESIS: Two reviewers
      independently selected reviews for inclusion, assessed their methodological
      quality, and extracted and synthesized data according to predefined criteria.
      Four systematic reviews finally were included. Based on single randomized
      controlled trials, there is some evidence of the effect of pain relief from
      topical capsaicin compared with placebo and for favorable functional outcomes for
      exercise and education compared with osteoarthritis information alone.
      LIMITATIONS: In overviews, results are dependent on available systematic reviews.
      They are important tools to guide choice of interventions and locate areas where
      more research is needed, but they might not be useful for deciding specifically
      how interventions should be carried out. CONCLUSIONS: There currently is
      insufficient high-quality evidence regarding nonpharmacological and nonsurgical
      interventions for hand osteoarthritis. Considering the limited research evidence
      and the prevalence and impact of the disease, there is an urgent need for more
      trials of nonpharmacological and nonsurgical interventions for hand
      osteoarthritis.

PMID- 19850714
TI  - miRGen 2.0: a database of microRNA genomic information and regulation.
AB  - MicroRNAs are small, non-protein coding RNA molecules known to regulate the
      expression of genes by binding to the 3'UTR region of mRNAs. MicroRNAs are
      produced from longer transcripts which can code for more than one mature miRNAs.
      miRGen 2.0 is a database that aims to provide comprehensive information about the
      position of human and mouse microRNA coding transcripts and their regulation by
      transcription factors, including a unique compilation of both predicted and
      experimentally supported data. Expression profiles of microRNAs in several
      tissues and cell lines, single nucleotide polymorphism locations, microRNA target
      prediction on protein coding genes and mapping of miRNA targets of co-regulated
      miRNAs on biological pathways are also integrated into the database and user
      interface. The miRGen database will be continuously maintained and freely
      available at http://www.microrna.gr/mirgen/.

PMID- 19850715
TI  - Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs.
AB  - Intercellular exchange of protein and RNA-containing microparticles is an
      increasingly important mode of cell-cell communication. Here we investigate if
      mesenchymal stem cells (MSCs) known for secreting therapeutic paracrine factors
      also secrete RNA-containing microparticles. We observed that human embryonic stem
      cell (hESC)-derived MSC conditioned medium contained small RNAs (less than 300
      nt) encapsulated in cholesterol-rich phospholipid vesicles as evidenced by their
      RNase sensitivity only in the presence of a sodium dodecyl sulfate-based cell
      lysis buffer, phospholipase A2 and a chelator of cholesterol, cyclodextrin and
      the restoration of their lower than expected density by detergent or
      phospholipase A2 treatment. MicroRNAs (miRNAs) such as hsa-let-7b and hsa-let-7g
      were present in a high precursor (pre)- to mature miRNA ratio by microarray
      analysis and quantitative reverse transcription-polymerase chain reaction. The
      pre-miRNAs were cleaved to mature miRNA by RNase III in vitro. High performance
      liquid chromatography-purified RNA-containing vesicles have a hydrodynamic radius
      of 55-65 nm and were readily taken up by H9C2 cardiomyocytes. This study suggests
      that MSCs could facilitate miRNA-mediated intercellular communication by
      secreting microparticles enriched for pre-miRNA.

PMID- 19850716
TI  - Comparing effects of mTR and mTERT deletion on gene expression and DNA damage
      response: a critical examination of telomere length maintenance-independent roles
      of telomerase.
AB  - Telomerase, the essential enzyme that maintains telomere length, contains two
      core components, TERT and TR. Early studies in yeast and mouse showed that loss
      of telomerase leads to phenotypes only after several generations, due to telomere
      shortening. However, recent studies have suggested additional roles for
      telomerase components in transcription and the response to DNA damage. To examine
      these potential telomere length maintenance-independent roles of telomerase
      components, we examined first generation mTR(-/-) and mTERT(-/-) mice with long
      telomeres. We used gene expression profiling and found no genes that were
      differentially expressed in mTR(-/-) G1 mice and mTERT(-/-) G1 mice compared with
      wild-type mice. We also compared the response to DNA damage in mTR(-/-)G1 and
      mTERT(-/-) G1 mouse embryonic fibroblasts, and found no increase in the response
      to DNA damage in the absence of either telomerase component compared to wild
      type. We conclude that, under physiologic conditions, neither mTR nor mTERT acts
      as a transcription factor or plays a role in the DNA damage response.

PMID- 19850717
TI  - NF90 selectively represses the translation of target mRNAs bearing an AU-rich
      signature motif.
AB  - The RNA-binding protein nuclear factor 90 (NF90) has been implicated in the
      stabilization, transport and translational control of several target mRNAs.
      However, a systematic analysis of NF90 target mRNAs has not been performed. Here,
      we use ribonucleoprotein immunoprecipitation analysis to identify a large subset
      of NF90-associated mRNAs. Comparison of the 3'-untranslated regions (UTRs) of
      these mRNAs led to the elucidation of a 25- to 30-nucleotide, RNA signature motif
      rich in adenines and uracils. Insertion of the AU-rich NF90 motif ('NF90m') in
      the 3'UTR of an EGFP heterologous reporter did not affect the steady-state level
      of the chimeric EGFP-NF90m mRNA or its cytosolic abundance. Instead, the
      translation of EGFP-NF90m mRNA was specifically repressed in an NF90-dependent
      manner, as determined by analysing nascent EGFP translation, the distribution of
      chimeric mRNAs on polysome gradients and the steady-state levels of expressed
      EGFP protein. The interaction of endogenous NF90 with target mRNAs was validated
      after testing both endogenous mRNAs and recombinant biotinylated transcripts
      containing NF90 motif hits. Further analysis showed that the stability of
      endogenous NF90 target mRNAs was not significantly influenced by NF90 abundance,
      while their translation increased when NF90 levels were reduced. In summary, we
      have identified an AU-rich RNA motif present in NF90 target mRNAs and have
      obtained evidence that NF90 represses the translation of this subset of mRNAs.

PMID- 19850718
TI  - The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection
      of pathway/genome databases.
AB  - The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible
      resource for metabolic pathways and enzymes from all domains of life. The
      pathways in MetaCyc are experimentally determined, small-molecule metabolic
      pathways and are curated from the primary scientific literature. With more than
      1400 pathways, MetaCyc is the largest collection of metabolic pathways currently
      available. Pathways reactions are linked to one or more well-characterized
      enzymes, and both pathways and enzymes are annotated with reviews, evidence
      codes, and literature citations. BioCyc (BioCyc.org) is a collection of more than
      500 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains
      the full genome and predicted metabolic network of one organism. The network,
      which is predicted by the Pathway Tools software using MetaCyc as a reference,
      consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs
      also contain additional features, such as predicted operons, transport systems,
      and pathway hole-fillers. The BioCyc Web site offers several tools for the
      analysis of the PGDBs, including Omics Viewers that enable visualization of omics
      datasets on two different genome-scale diagrams and tools for comparative
      analysis. The BioCyc PGDBs generated by SRI are offered for adoption by any party
      interested in curation of metabolic, regulatory, and genome-related information
      about an organism.

PMID- 19850719
TI  - A systematic molecular dynamics study of nearest-neighbor effects on base pair
      and base pair step conformations and fluctuations in B-DNA.
AB  - It is well recognized that base sequence exerts a significant influence on the
      properties of DNA and plays a significant role in protein-DNA interactions vital
      for cellular processes. Understanding and predicting base sequence effects
      requires an extensive structural and dynamic dataset which is currently
      unavailable from experiment. A consortium of laboratories was consequently formed
      to obtain this information using molecular simulations. This article describes
      results providing information not only on all 10 unique base pair steps, but also
      on all possible nearest-neighbor effects on these steps. These results are
      derived from simulations of 50-100 ns on 39 different DNA oligomers in explicit
      solvent and using a physiological salt concentration. We demonstrate that the
      simulations are converged in terms of helical and backbone parameters. The
      results show that nearest-neighbor effects on base pair steps are very
      significant, implying that dinucleotide models are insufficient for predicting
      sequence-dependent behavior. Flanking base sequences can notably lead to base
      pair step parameters in dynamic equilibrium between two conformational sub
      states. Although this study only provides limited data on next-nearest-neighbor
      effects, we suggest that such effects should be analyzed before attempting to
      predict the sequence-dependent behavior of DNA.

PMID- 19850720
TI  - Modeling tissue-specific structural patterns in human and mouse promoters.
AB  - Sets of genes expressed in the same tissue are believed to be under the
      regulation of a similar set of transcription factors, and can thus be assumed to
      contain similar structural patterns in their regulatory regions. Here we present
      a study of the structural patterns in promoters of genes expressed specifically
      in 26 human and 34 mouse tissues. For each tissue we constructed promoter
      structure models, taking into account presences of motifs, their positioning to
      the transcription start site, and pairwise positioning of motifs. We found that
      35 out of 60 models (58%) were able to distinguish positive test promoter
      sequences from control promoter sequences with statistical significance. Models
      with high performance include those for liver, skeletal muscle, kidney and
      tongue. Many of the important structural patterns in these models involve
      transcription factors of known importance in the tissues in question and
      structural patterns tend to be conserved between human and mouse. In addition to
      that, promoter models for related tissues tend to have high inter-tissue
      performance, indicating that their promoters share common structural patterns.
      Together, these results illustrate the validity of our models, but also indicate
      that the promoter structures for some tissues are easier to model than those of
      others.

PMID- 19850721
TI  - Molecular dynamics simulations and coupled nucleotide substitution experiments
      indicate the nature of A{middle dot}A base pairing and a putative structure of
      the coralyne-induced homo-adenine duplex.
AB  - Coralyne is an alkaloid drug that binds homo-adenine DNA (and RNA)
      oligonucleotides more tightly than it does Watson-Crick DNA. Hud's laboratory has
      shown that poly(dA) in the presence of coralyne forms an anti-parallel duplex,
      however attempts to determine the structure by NMR spectroscopy and X-ray
      crystallography have been unsuccessful. Assuming adenine-adenine hydrogen bonding
      between the two poly(dA) strands, we constructed 40 hypothetical homo-(dA) anti
      parallel duplexes and docked coralyne into the six most favorable duplex
      structures. The two most stable structures had trans glycosidic bonds, but
      distinct pairing geometries, i.e. either Watson-Crick Hoogsteen (transWH) or
      Watson-Crick Watson-Crick (transWW) with stability of transWH > transWW. To
      narrow down the possibilities, 7-deaza adenine base substitutions (dA-->7) were
      engineered into homo-(dA) sequences. These substitutions significantly reduced
      the thermal stability of the coralyne-induced homo-(dA) structure. These
      experiments strongly suggest the involvement of N7 in the coralyne-induced A.A
      base pairs. Moreover, due to the differential effect on melting as a function of
      the location of the dA-->7 mutations, these results are consistent with the N1-N7
      base pairing of the transWH pairs. Together, the simulation and base substitution
      experiments predict that the coralyne-induced homo-(dA) duplex structure adopts
      the transWH geometry.

PMID- 19850722
TI  - GeMInA, Genomic Metadata for Infectious Agents, a geospatial surveillance
      pathogen database.
AB  - The Gemina system (http://gemina.igs.umaryland.edu) identifies, standardizes and
      integrates the outbreak metadata for the breadth of NIAID category A-C viral and
      bacterial pathogens, thereby providing an investigative and surveillance tool
      describing the Who [Host], What [Disease, Symptom], When [Date], Where [Location]
      and How [Pathogen, Environmental Source, Reservoir, Transmission Method] for each
      pathogen. The Gemina database will provide a greater understanding of the
      interactions of viral and bacterial pathogens with their hosts and infectious
      diseases through in-depth literature text-mining, integrated outbreak metadata,
      outbreak surveillance tools, extensive ontology development, metadata curation
      and representative genomic sequence identification and standards development. The
      Gemina web interface provides metadata selection and retrieval of a pathogen's;
      Infection Systems (Pathogen, Host, Disease, Transmission Method and Anatomy) and
      Incidents (Location and Date) along with a hosts Age and Gender. The Gemina
      system provides an integrated investigative and geospatial surveillance system
      connecting pathogens, pathogen products and disease anchored on the taxonomic ID
      of the pathogen and host to identify the breadth of hosts and diseases known for
      these pathogens, to identify the extent of outbreak locations, and to identify
      unique genomic regions with the DNA Signature Insignia Detection Tool.

PMID- 19850723
TI  - The IntAct molecular interaction database in 2010.
AB  - IntAct is an open-source, open data molecular interaction database and toolkit.
      Data is abstracted from the literature or from direct data depositions by expert
      curators following a deep annotation model providing a high level of detail. As
      of September 2009, IntAct contains over 200.000 curated binary interaction
      evidences. In response to the growing data volume and user requests, IntAct now
      provides a two-tiered view of the interaction data. The search interface allows
      the user to iteratively develop complex queries, exploiting the detailed
      annotation with hierarchical controlled vocabularies. Results are provided at any
      stage in a simplified, tabular view. Specialized views then allows 'zooming in'
      on the full annotation of interactions, interactors and their properties. IntAct
      source code and data are freely available at http://www.ebi.ac.uk/intact.

PMID- 19850725
TI  - DDBJ launches a new archive database with analytical tools for next-generation
      sequence data.
AB  - The DNA Data Bank of Japan (DDBJ) (http://www.ddbj.nig.ac.jp) has collected and
      released 1,701,110 entries/1,116,138,614 bases between July 2008 and June 2009. A
      few highlighted data releases from DDBJ were the complete genome sequence of an
      endosymbiont within protist cells in the termite gut and Cap Analysis Gene
      Expression tags for human and mouse deposited from the Functional Annotation of
      the Mammalian cDNA consortium. In this period, we started a novel user
      announcement service using Really Simple Syndication (RSS) to deliver a list of
      data released from DDBJ on a daily basis. Comprehensive visualization of a DDBJ
      release data was attempted by using a word cloud program. Moreover, a new archive
      for sequencing data from next-generation sequencers, the 'DDBJ Read Archive'
      (DRA), was launched. Concurrently, for read data registered in DRA, a semi
      automatic annotation tool called the 'DDBJ Read Annotation Pipeline' was released
      as a preliminary step. The pipeline consists of two parts: basic analysis for
      reference genome mapping and de novo assembly and high-level analysis of
      structural and functional annotations. These new services will aid users'
      research and provide easier access to DDBJ databases.

PMID- 19850724
TI  - Sequence context outside the target region influences the effectiveness of miR
      223 target sites in the RhoB 3'UTR.
AB  - MicroRNAs (miRNAs) are 21-22 nucleotide regulatory small RNAs that repress
      message translation via base-pairing with complementary sequences in the 3'
      untranslated region (3'UTR) of targeted transcripts. To date, it is still
      difficult to find a true miRNA target due to lack of a clear understanding of how
      miRNAs functionally interact with their targeted transcripts for efficient
      repression. Previous studies have shown that nucleotides 2 to 7 at the 5'-end of
      a mature miRNA, the 'seed sequence', can nucleate miRNA/target interactions. In
      the current study, we have validated that the RhoB mRNA is a bona fide miR-223
      target. We have analyzed the functional activities of two miR223-binding sites
      within the RhoB 3'UTR. We find that the two miR-223 target sites in the RhoB
      3'UTR contribute differentially to the total repression of RhoB translation.
      Moreover, we demonstrate that some AU-rich motifs located upstream of the distal
      miRNA-binding site enhance miRNA function, independent of the miRNA target
      sequences being tested. We also demonstrate that the AU-rich sequence elements
      are polar, and do not affect the activities of miRNAs whose sites lie upstream of
      these elements. These studies provide further support for the role of sequences
      outside of miRNA target region influencing miRNA function.

PMID- 19850726
TI  - Bubble-induced platelet aggregation in a rat model of decompression sickness.
AB  - Previous studies have highlighted that bubble-induced platelet aggregation is a
      predictor index of decompression sickness (DCS) severity in animals and bubble
      formation after a single air dive in humans. The present study attempted to
      investigate plasmatic indexes of the coagulation system and platelet activation
      in our rat model of DCS. Male Sprague-Dawley rats were assigned to one
      experimental group with a hyperbaric exposure and one control group maintained at
      atmospheric pressure. Rats were compressed to 1,000 kPa (90 m saltwater) for 45
      min while breathing air. The onset of death time and DCS symptoms were recorded
      during a 30-min observed period after rats had surfaced. Plasmatic indexes were
      platelet factor 4 (PF4) for platelet activation, soluble glycoprotein V (sGPV)
      for thrombin generation, and thrombin-antithrombin complexes for the coagulation
      system. Blood samples for a platelet count and markers were taken 3 wk before the
      experimental protocol and within the 30 min after rats had surfaced. We confirmed
      a correlation between the percent fall in platelet count and DCS severity.
      Plasmatic levels of sGPV and PF4 were significantly increased after the
      hyperbaric exposure, with no change in the control group. The present study
      confirms platelet consumption as a potential index for evaluating decompression
      stress and DCS severity. The results point to the participation of thrombin
      generation in the coagulation cascade and platelet activation in bubble-induced
      platelet aggregation. In our animal model of DCS, the results cannot prejudge the
      mechanisms of platelet activation between bubble-induced vessel wall injury and
      bubble-blood component interactions.

PMID- 19850727
TI  - Endurance exercise training effects on body fatness, VO2max, HDL-C subfractions,
      and glucose tolerance are influenced by a PLIN haplotype in older Caucasians.
AB  - Perilipins are lipid droplet-coating proteins that regulate intracellular
      lipolysis in adipocytes. A haplotype of two perilipin gene (PLIN) single
      nucleotide polymorphisms, 13041A>G and 14995A>T, has been previously associated
      with obesity risk. Furthermore, the available data indicate that this association
      may be modified by sex. We hypothesized that this haplotype would associate with
      body fatness, aerobic fitness, and a number of cardiovascular (CV) risk factor
      phenotypes before and after a 6-mo endurance exercise training program in
      sedentary older Caucasians. The major haplotype group (13041A/14995A; n = 57) had
      significantly lower body mass index (BMI) and body fatness compared with
      noncarriers of the AA haplotype (n = 44) before the training intervention.
      Training improved body composition in both groups, but fatness remained higher in
      noncarriers than AA carriers after training. This fat retention in noncarriers
      blunted their maximal oxygen uptake (Vo(2 max)) adaptation to training. Female
      noncarriers had substantially higher concentrations of several conventionally and
      NMR-measured HDL-C subfractions than male noncarriers before and after training,
      but only minimal differences were found between the sexes in the AA haplotype
      group. Haplotype group differences in baseline and after-training responses to an
      oral glucose tolerance test (OGTT) also differed by sex, as noncarrier men had
      the highest baseline area under the insulin curve (insulin AUC), but were the
      only group to significantly improve insulin AUC with training. The insulin
      sensitivity index and plasma glucose responses to the OGTT were more favorable in
      AA carriers than noncarriers before and after training. Overall, our findings
      suggest that PLIN variation explains some of the interindividual differences in
      the response of obesity and CV phenotypes to exercise training. Furthermore,
      these data contribute to the growing understanding of PLIN as a candidate gene
      for human obesity and the cardiometabolic consequences of excess adiposity.

PMID- 19850728
TI  - Involvement of matrix metalloproteinases in the growth plate response to
      physiological mechanical load.
AB  - Enzymes from the matrix metalloproteinase (MMP) family play a crucial role in
      growth-plate vascularization and ossification via proteolytic cleavage and
      remodeling of the extracellular matrix. Their regulation in the growth plate is
      crucial for normal matrix assembly. Endochondral ossification, which takes place
      at the growth plates, is influenced by mechanical loading. Using an in vivo avian
      model for mechanical loading, we have found increased blood penetration into the
      growth plates of loaded chicks. The purpose of this work was to study the
      involvement of MMP-2, -3, -9, -13, and -16 in the growth plate's response to
      loading and in the catch-up growth resulting from load release. We found that
      mechanical loading, as well as release from load, upregulated MMP-2, -9, and -13
      expressions. In contrast, MMP-3, associated with cartilage injuries, and its
      associated protein connective tissue growth factor (CTGF), were downregulated by
      the load. However, after release from load, MMP-3 was upregulated and CTGF levels
      were elevated and caught up with the control. MMP-3 and CTGF were also
      downregulated after 60 min of mechanical stretching in vitro. These results
      demonstrate the central role of MMPs in the growth plate's response to mechanical
      loading, as well as in the catch-up growth followed load release.

PMID- 19850729
TI  - Effect of oxygen breathing and perfluorocarbon emulsion treatment on air bubbles
      in adipose tissue during decompression sickness.
AB  - Decompression sickness (DCS) after air diving has been treated with success by
      means of combined normobaric oxygen breathing and intravascular perfluorocarbon
      (PFC) emulsions causing increased survival rate and faster bubble clearance from
      the intravascular compartment. The beneficial PFC effect has been explained by
      the increased transport capacity of oxygen and inert gases in blood. However,
      previous reports have shown that extravascular bubbles in lipid tissue of rats
      suffering from DCS will initially grow during oxygen breathing at normobaric
      conditions. We hypothesize that the combined effect of normobaric oxygen
      breathing and intravascular PFC infusion could lead to either enhanced
      extravascular bubble growth on decompression due to the increased oxygen supply,
      or that PFC infusion could lead to faster bubble elimination due to the increased
      solubility and transport capacity in blood for nitrogen causing faster nitrogen
      tissue desaturation. In anesthetized rats decompressed from a 60-min hyperbaric
      exposure breathing air at 385 kPa, we visually followed the resolution of micro
      air bubbles injected into abdominal adipose tissue while the rats breathed either
      air, oxygen, or oxygen breathing combined with PFC infusion. All bubble
      observations were done at 101.3 kPa pressure. During oxygen breathing with or
      without combined PFC infusion, bubbles disappeared faster compared with air
      breathing. Combined oxygen breathing and PFC infusion caused faster bubble
      disappearance compared with oxygen breathing. The combined effect of oxygen
      breathing and PFC infusion neither prevented nor increased transient bubble
      growth time, rate, or growth ratio compared with oxygen breathing alone. We
      conclude that oxygen breathing in combination with PFC infusion causes faster
      bubble disappearance and does not exacerbate transient bubble growth. PFC
      infusion may be a valuable adjunct therapy during the first-aid treatment of DCS
      at normobaric conditions.

PMID- 19850730
TI  - Control of gluconeogenic genes during intense/prolonged exercise: hormone
      independent effect of muscle-derived IL-6 on hepatic tissue and PEPCK mRNA.
AB  - Prolonged intense exercise is challenging for the liver to maintain plasma
      glucose levels. Hormonal changes cannot fully account for exercise-induced
      hepatic glucose production (HGP). Contracting skeletal muscles release
      interleukin-6 (IL-6), a cytokine able to increase endogenous glucose production
      during exercise. However, whether this is attributable to a direct effect of IL-6
      on liver remains unknown. Here, we studied hepatic glycogen, gluconeogenic genes,
      and IL-6 signaling in response to one bout of exhaustive running exercise in
      rats. To determine whether IL-6 can modulate gluconeogenic gene mRNA
      independently of exercise, we injected resting rats with recombinant IL-6.
      Exhaustive exercise resulted in a profound decrease in liver glycogen and an
      increase in gluconeogenic gene mRNA levels, phosphoenolpyruvate-carboxykinase
      (PEPCK), glucose-6-phosphatase (G6P), and peroxisome proliferator-activated
      receptor-gamma coactivator-1alpha (PGC-1alpha), suggesting a key role for
      gluconeogenesis in hepatic glucose production. This was associated to an active
      IL-6 signaling in liver tissue, as shown by signal transducer and activator of
      transcription and CAAT/enhancer binding protein-beta phosphorylation and IL-6
      responsive gene mRNA levels at the end of exercise. Recombinant IL-6 injection
      resulted in an increase in IL-6-responsive gene mRNA levels in the liver. We
      found a dose-dependent increase in PEPCK gene mRNA strongly correlated with IL-6
      induced gene mRNA levels. No changes in G6P and PGC-1alpha mRNA levels were
      found. Taken together, our results suggest that, during very demanding exercise,
      muscle-derived IL-6 could help increase HGP by directly upregulating PEPCK mRNA
      abundance.

PMID- 19850731
TI  - Spaceflight modulates expression of extracellular matrix, adhesion, and
      profibrotic molecules in mouse lung.
AB  - NASA has reported pulmonary abnormalities in astronauts on space missions, but
      the molecular changes in lung tissue remain unknown. The goal of the present
      study was to explore the effects of spaceflight on expression of extracellular
      matrix (ECM), cell adhesion, and pro-fibrotic molecules in lungs of mice flown on
      Space Shuttle Endeavour (STS-118). C57BL/6Ntac mice housed in animal enclosure
      modules during a 13-day mission in space (FLT) were killed within hours after
      return; ground controls were treated similarly for comparison (GRD). Analysis of
      genes associated with ECM and adhesion molecules was performed according to
      quantitative RT-PCR. The data revealed that FLT lung samples had statistically
      significant transcriptional changes, i.e., at least 1.5-fold, in 25 out of 84
      examined genes (P < 0.05); 15 genes were upregulated and 10 were downregulated.
      The genes that were upregulated by more than twofold were Ctgf, Mmp2, Ncam1,
      Sparc, Spock1, and Timp3, whereas the most downregulated genes were Lama1, Mmp3,
      Mmp7, vcam-1, and Sele. Histology showed profibrosis-like changes occurred in FLT
      mice, more abundant collagen accumulation around blood vessels, and thicker walls
      compared with lung samples from GRD mice. Immunohistochemistry was used to
      compare expression of six selected proteins associated with fibrosis.
      Immunoreactivity of four proteins (MMP-2, CTGF, TGF-beta1, and NCAM) was enhanced
      by spaceflight, whereas, no difference was detected in expression of MMP-7 and
      MMP-9 proteins between the FLT and GRD groups. Taken together, the data
      demonstrate that significant changes can be readily detected shortly after return
      from spaceflight in the expression of factors that can adversely influence lung
      function.

PMID- 19850732
TI  - Time course expression of Foxo transcription factors in skeletal muscle following
      corticosteroid administration.
AB  - Increased expression of forkhead box O (Foxo) transcription factors were reported
      in cultured myotubes and mouse limb muscle with corticosteroid (CS) treatment. We
      previously reported that administration of CS to rats resulted in muscle fiber
      atrophy only by day 7. The aim of this study, therefore, was to evaluate the time
      course changes in the expression of Foxo transcription factors and muscle
      specific ubiquitin E3 ligases in rat limb muscle following CS administration.
      Triamcinolone (TRI; 1 mg x kg(-1) x day(-1) im) was administered for 1, 3, or 7
      days. Control (CTL) rats were given saline. Muscle mRNA was analyzed by real-time
      RT-PCR. Compared with CTL, body weights of TRI-treated animals decreased by 3,
      12, and 21% at days 1, 3, and 7, respectively. Muscle IGF-1 mRNA levels decreased
      by 33, 65, and 58% at days 1, 3, and 7 in TRI-treated rats compared with CTL.
      Levels of phosphorylated Akt were 28, 50, and 36% lower in TRI animals at these
      time points. Foxo1 mRNA increased progressively by 1.2-, 1.4-, and 2.5-fold at
      days 1, 3, and 7 in TRI animals. Similar changes were noted in the expression of
      Foxo3a mRNA (1.3-, 1.4-, and 2.6-fold increments). By contrast, Foxo4 mRNA was
      not significantly changed in TRI animals. With TRI, muscle atrophy F box/Atrogin
      1 increased by 1.8-, 4.1-, and 7.5-fold at days 1, 3, and 7 compared with CTL
      rats. By contrast, muscle RING finger 1 increased only from day 7 (2.7-fold).
      Gradual reduction in IGF-I expression with TRI over the time series paralleled
      that of Akt. These findings are consistent with a progressive stimulus to muscle
      protein degradation and the need to process/remove disassembled muscle proteins
      via the ubiquitin-proteasome system. Elucidating the dynamic catabolic responses
      to CS challenge is important in understanding the mechanisms underlying muscle
      atrophy and therapeutic measures to offset this.

PMID- 19850733
TI  - Rap1 mediates protective effects of iloprost against ventilator-induced lung
      injury.
AB  - Prostaglandin I(2) (PGI(2)) has been shown to attenuate vascular constriction,
      hyperpermeability, inflammation, and acute lung injury. However, molecular
      mechanisms of PGI(2) protective effects on pulmonary endothelial cells (EC) are
      not well understood. We tested a role of cAMP-activated Epac-Rap1 pathway in the
      barrier protective effects of PGI(2) analog iloprost in the murine model of
      ventilator-induced lung injury. Mice were treated with iloprost (2 microg/kg)
      after onset of high tidal volume ventilation (30 ml/kg, 4 h). Bronchoalveolar
      lavage, histological analysis, and measurements of Evans blue accumulation were
      performed. In vitro, microvascular EC barrier function was assessed by
      morphological analysis of agonist-induced gap formation and monitoring of Rho
      pathway activation and EC permeability. Iloprost reduced bronchoalveolar lavage
      protein content, neutrophil accumulation, capillary filtration coefficient, and
      Evans blue albumin extravasation caused by high tidal volume ventilation. Small
      interfering RNA-based Rap1 knockdown inhibited protective effects of iloprost. In
      vitro, iloprost increased barrier properties of lung microvascular endothelium
      and alleviated thrombin-induced EC barrier disruption. In line with in vivo
      results, Rap1 depletion attenuated protective effects of iloprost in the thrombin
      model of EC permeability. These data describe for the first time protective
      effects for Rap1-dependent signaling against ventilator-induced lung injury and
      pulmonary endothelial barrier dysfunction.

PMID- 19850734
TI  - Influence of cardiac shape on left ventricular twist.
AB  - The dynamic interaction between subendocardial and subepicardial fibre helices in
      the left ventricle (LV) leads to a twisting deformation, which has an important
      role in LV function. This study sought to assess the influence of cardiac shape
      on LV twist in the normal and dilated human heart. The study comprised 45 dilated
      cardiomyopathy (DCM) patients and 60 for age- and gender-matched healthy
      volunteers. Speckle tracking echocardiography was used to determine basal and
      apical LV peak systolic rotation (Rot(max)) and instantaneous LV peak systolic
      twist (Twist(max)). LV sphericity index was calculated by dividing the LV maximal
      long-axis internal dimension by the maximal short-axis internal dimension at end
      diastole. A parabolic relation between the sphericity index and apical Rot(max)
      or Twist(max) was identified in the total study population (R(2) = 0.56 and R(2)
      = 0.54, respectively; both P < 0.001) and healthy volunteers (R(2) = 0.39 and
      R(2) = 0.25, respectively; both P < 0.001), whereas these relations were linear
      in DCM patients (R(2) = 0.40 and R(2) = 0.43, respectively; both P < 0.001). In a
      multivariate analysis, LV sphericity index was the strongest independent
      predictor of apical Rot(max) and Twist(max). In conclusion, LV apical rotation
      and twist are significantly influenced by LV configuration. Taking the important
      function of LV twist into account, this finding highlights the vital influence of
      cardiac shape on LV systolic function.

PMID- 19850735
TI  - Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle
      size, and functional performance in middle-aged and older men: an 18-mo
      randomized controlled trial.
AB  - Limited data have suggested that the consumption of fluid milk after resistance
      training (RT) may promote skeletal muscle hypertrophy. The aim of this study was
      to assess whether a milk-based nutritional supplement could enhance the effects
      of RT on muscle mass, size, strength, and function in middle-aged and older men.
      This was an 18-mo factorial design (randomized control trial) in which 180
      healthy men aged 50-79 yr were allocated to the following groups: 1) exercise +
      fortified milk, 2) exercise, 3) fortified milk, or 4) control. Exercise consisted
      of progressive RT with weight-bearing impact exercise. Men assigned to the
      fortified milk consumed 400 ml/day of low-fat milk, providing an additional 836
      kJ, 1000 mg calcium, 800 IU vitamin D(3), and 13.2 g protein per day. Total body
      lean mass (LM) and fat mass (FM) (dual-energy X-ray absorptiometry), midfemur
      muscle cross-sectional area (CSA) (quantitative computed tomography), muscle
      strength, and physical function were assessed. After 18 mo, there was no
      significant exercise by fortified milk interaction for total body LM, muscle CSA,
      or any functional measure. However, main effect analyses revealed that exercise
      significantly improved muscle strength ( approximately 20-52%, P < 0.001), LM
      (0.6 kg, P < 0.05), FM (-1.1 kg, P < 0.001), muscle CSA (1.8%, P < 0.001), and
      gait speed (11%, P < 0.05) relative to no exercise. There were no effects of the
      fortified milk on muscle size, strength, or function. In conclusion, the daily
      consumption of low-fat fortified milk does not enhance the effects of RT on
      skeletal muscle size, strength, or function in healthy middle-aged and older men
      with adequate energy and nutrient intakes.

PMID- 19850736
TI  - Involuntary breathing movements improve cerebral oxygenation during apnea
      struggle phase in elite divers.
AB  - We investigated whether the involuntary breathing movements (IBM) during the
      struggle phase of breath holding, together with peripheral vasoconstriction and
      progressive hypercapnia, have a positive effect in maintaining cerebral blood
      volume. The central hemodynamics, arterial oxygen saturation, brain regional
      oxyhemoglobin (bHbO(2)), deoxyhemoglobin, and total hemoglobin changes and IBM
      were monitored during maximal dry breath holds in eight elite divers. The
      frequency of IBM increased (by approximately 100%), and their duration decreased
      ( approximately 30%), toward the end of the struggle phase, whereas the amplitude
      was unchanged (compared with the beginning of the struggle phase). In all
      subjects, a consistent increase in brain regional deoxyhemoglobin and total
      hemoglobin was also found during struggle phase, whereas bHbO(2) changed
      biphasically: it initially increased until the middle of the struggle phase, with
      the subsequent relative decline at the end of the breath hold. Mean arterial
      pressure was elevated during the struggle phase, although there was no further
      rise in the peripheral resistance, suggesting unchanged peripheral
      vasoconstriction and implying the beneficial influence of the IBM on the cardiac
      output recovery (primarily by restoration of the stroke volume). The IBM-induced
      short-lasting, sudden increases in mean arterial pressure were followed by
      similar oscillations in bHbO(2). These results suggest that an increase in the
      cerebral blood volume observed during the struggle phase of dry apnea is most
      likely caused by the IBM at the time of the hypercapnia-induced cerebral
      vasodilatation and peripheral vasoconstriction.

PMID- 19850737
TI  - AML1/RUNX1 point mutation possibly promotes leukemic transformation in
      myeloproliferative neoplasms.
AB  - Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders
      characterized by proliferation of one or more myeloid cell lineages. Some
      patients exhibit leukemic transformation (LT) by unknown mechanisms, and
      chemotherapy may increase the risk of LT. To clarify the molecular mechanisms of
      LT, gene alterations involved in LT from patients in the chronic phase (CP) of
      MPNs were identified. Among 18 patients who progressed to leukemia, AML1/RUNX1
      mutations were detected in 5 patients at the LT but in none at the CP. To
      investigate the leukemogenic effect of AML1/RUNX1 mutants, the AML1D171N mutant
      was transduced into CD34(+) cells from patients in the CP of MPNs. The D171N
      transduction resulted in proliferation of immature myeloid cells, enhanced self
      renewal capacity, and proliferation of primitive progenitors. Taken together,
      these results indicate that AML1/RUNX1 point mutations may have a leukemogenic
      potential in MPN stem cells, and they may promote leukemic transformation in MPN.

PMID- 19850738
TI  - How I treat CLL up front.
AB  - Although chronic lymphocytic leukemia (CLL) remains incurable, over the past
      decade there have been major advances in understanding the pathophysiology of CLL
      and in the treatment of this disease. This has led to greatly increased response
      rates and durations of response but not yet improved survival. Advances in the
      use of prognostic factors that identify patients at high risk for progression
      have led us to the question whether there is still a role for a "watch and wait"
      approach in asymptomatic high-risk patients or whether they should be treated
      earlier in their disease course. Questions remain, including, what is the optimal
      first-line treatment and its timing and is there any role of maintenance therapy
      or stem cell transplantation in this disease? CLL is a disease of the elderly and
      not all patients are eligible for aggressive up-front chemoimmunotherapy
      regimens, so what is the optimal treatment approach for more frail elderly
      patients? It is highly likely that our treatment approaches will continue to
      evolve as the results of ongoing clinical trials are released and that further
      improvements in the outcome of this disease will result from identification of
      therapies that target the underlying pathophysiology of CLL.

PMID- 19850739
TI  - Identification of proapoptotic Bim as a tumor suppressor in neoplastic mast
      cells: role of KIT D816V and effects of various targeted drugs.
AB  - Systemic mastocytosis (SM) is a myeloid neoplasm involving mast cells (MCs) and
      their progenitors. In most cases, neoplastic cells display the D816V-mutated
      variant of KIT. KIT D816V exhibits constitutive tyrosine kinase (TK) activity and
      has been implicated in increased survival and growth of neoplastic MCs. Recent
      data suggest that the proapoptotic BH3-only death regulator Bim plays a role as a
      tumor suppressor in various myeloid neoplasms. We found that KIT D816V suppresses
      expression of Bim in Ba/F3 cells. The KIT D816-induced down-regulation of Bim was
      rescued by the KIT-targeting drug PKC412/midostaurin. Both PKC412 and the
      proteasome-inhibitor bortezomib were found to decrease growth and promote
      expression of Bim in MC leukemia cell lines HMC-1.1 (D816V negative) and HMC-1.2
      (D816V positive). Both drugs were also found to counteract growth of primary
      neoplastic MCs. Furthermore, midostaurin was found to cooperate with bortezomib
      and with the BH3-mimetic obatoclax in producing growth inhibition in both HMC-1
      subclones. Finally, a Bim-specific siRNA was found to rescue HMC-1 cells from
      PKC412-induced cell death. Our data show that KIT D816V suppresses expression of
      proapoptotic Bim in neoplastic MCs. Targeting of Bcl-2 family members by drugs
      promoting Bim (re)-expression, or by BH3-mimetics such as obatoclax, may be an
      attractive therapy concept in SM.

PMID- 19850740
TI  - Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic
      leukemia: selection, impact on survival, and response to DNA damage.
AB  - Deletion of TP53 gene, under routine assessment by fluorescence in situ
      hybridization analysis, connects with the worst prognosis in chronic lymphocytic
      leukemia (CLL). The presence of isolated TP53 mutation (without deletion) is
      associated with reduced survival in CLL patients. It is unclear how these
      abnormalities are selected and what their mutual proportion is. We used
      methodologies with similar sensitivity for the detection of deletions (interphase
      fluorescence in situ hybridization) and mutations (yeast functional analysis) and
      analyzed a large consecutive series of 400 CLL patients; a subset of p53-wild
      type cases (n = 132) was screened repeatedly during disease course. The most
      common type of TP53 inactivation, ie, mutation accompanied by deletion of the
      remaining allele, occurred in 42 patients (10.5%). Among additional defects, the
      frequency of the isolated TP53 mutation (n = 20; 5%) and the combination of 2 or
      more mutations on separate alleles (n = 5; 1.3%) greatly exceeded the sole
      deletion (n = 3; 0.8%). Twelve patients manifested defects during repeated
      investigation; in all circumstances the defects involved mutation and occurred
      after therapy. Monoallelic defects had a negative impact on survival and impaired
      in vitro response to fludarabine. Mutation analysis of the TP53 should be
      performed before each treatment initiation because novel defects may be selected
      by previous therapies.

PMID- 19850741
TI  - MicroRNA 29b functions in acute myeloid leukemia.
AB  - MicroRNAs (miRNAs) are associated with cytogenetics and molecular subtypes of
      acute myelogeneous leukemia (AML), but their impact on AML pathogenesis is poorly
      understood. We have previously shown that miR-29b expression is deregulated in
      primary AML blasts. In this work, we investigated the functional role of miR-29b
      in leukemogenesis. Restoration of miR-29b in AML cell lines and primary samples
      induces apoptosis and dramatically reduces tumorigenicity in a xenograft leukemia
      model. Transcriptome analysis after ectopic transfection of synthetic miR-29b
      into leukemia cells indicates that miR-29b target apoptosis, cell cycle, and
      proliferation pathways. A significant enrichment for apoptosis genes, including
      MCL-1, was found among the mRNAs inversely correlated with miR-29b expression in
      45 primary AML samples. Together, the data support a tumor suppressor role for
      miR-29 and provide a rationale for the use of synthetic miR-29b oligonucleotides
      as a novel strategy to improve treatment response in AML.

PMID- 19850742
TI  - Scl regulates the quiescence and the long-term competence of hematopoietic stem
      cells.
AB  - The majority of long-term reconstituting hematopoietic stem cells (LT-HSCs) in
      the adult is in G(0), whereas a large proportion of progenitors are more cycling.
      We show here that the SCL/TAL1 transcription factor is highly expressed in LT
      HSCs compared with short-term reconstituting HSCs and progenitors and that SCL
      negatively regulates the G(0)-G(1) transit of LT-HSCs. Furthermore, when SCL
      protein levels are decreased by gene targeting or by RNA interference, the
      reconstitution potential of HSCs is impaired in several transplantation assays.
      First, the mean stem cell activity of HSCs transplanted at approximately 1
      competitive repopulating unit was 2-fold decreased when Scl gene dosage was
      decreased. Second, Scl(+/-) HSCs were at a marked competitive disadvantage with
      Scl(+/+) cells when transplanted at 4 competitive repopulating units equivalent.
      Third, reconstitution of the stem cell pool by adult HSCs expressing Scl-directed
      shRNAs was decreased compared with controls. At the molecular level, we found
      that SCL occupies the Cdkn1a and Id1 loci in primary hematopoietic cells and that
      the expression levels of these 2 regulators of HSC cell cycle and long-term
      functions are sensitive to Scl gene dosage. Together, our observations suggest
      that SCL impedes G(0)-G(1) transition in HSCs and regulates their long-term
      competence.

PMID- 19850743
TI  - TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.
AB  - Tumor necrosis factor alpha (TNF-alpha) production is abnormally high in Fanconi
      anemia (FA) cells and contributes to the hematopoietic defects seen in FA
      complementation group C-deficient (Fancc(-/-)) mice. Applying gene expression
      microarray and proteomic methods to studies on FANCC-deficient cells we found
      that genes encoding proteins directly involved in ubiquitinylation are
      overrepresented in the signature of FA bone marrow cells and that
      ubiquitinylation profiles of FA-C and complemented cells were substantially
      different. Finding that Toll-like receptor 8 (TLR8) was one of the proteins
      ubiquitinylated only in mutant cells, we confirmed that TLR8 (or a TLR8
      associated protein) is ubiquitinylated in mutant FA-C cells and that TNF-alpha
      production in mutant cells depended upon TLR8 and the canonical downstream
      signaling intermediates interleukin 1 receptor-associated kinase (IRAK) and
      IkappaB kinase-alpha/beta. FANCC-deficient THP-1 cells and macrophages from
      Fancc(-/-) mice overexpressed TNF-alpha in response to TLR8 agonists but not
      other TLR agonists. Ectopically expressed FANCC point mutants were capable of
      fully complementing the mitomycin-C hypersensitivity phenotype of FA-C cells but
      did not suppress TNF-alpha overproduction. In conclusion, FANCC suppresses TNF
      alpha production in mononuclear phagocytes by suppressing TLR8 activity and this
      particular function of FANCC is independent of its function in protecting the
      genome from cross-linking agents.

PMID- 19850744
TI  - Small ubiquitin-like modifier-2 modification of retinoic acid receptor-alpha
      regulates its subcellular localization and transcriptional activity.
AB  - The retinoic acid receptor-alpha (Rara) gene is critical for germ cell
      development in the testis, as demonstrated by infertile Rara knockout male mice.
      The encoded protein for Rara (RARA) is expressed in both Sertoli cells and germ
      cells, but it is not always in the nucleus. Previously, all-trans retinoic acid
      (ATRA) was shown to increase the nuclear localization and transcriptional
      activity of RARA in Sertoli cells. Here, we identified a small ubiquitin-like
      modifier-2 (SUMO-2) modification as a novel posttranslational regulatory
      mechanism controlling the ATRA-dependent RARA subcellular localization and
      transcription. ATRA increased the SUMO-2 modification of RARA. In the presence of
      ATRA, lysine 166 (K166) and K171 of RARA were modified at a physiological
      concentration of SUMO-2, whereas in the absence of ATRA, K399 was the only site
      that was modified, but at a higher SUMO-2 concentration. However, K399 was
      critical for ATRA-controlled nuclear trafficking of RARA. In the presence of
      ATRA, a K399 mutation to arginine resulted in the cytoplasmic localization of
      K399R mutant, indicating that K166 and K171 sumoylations were inhibitory to
      nuclear localization. This may be due to SUMO/sentrin-specific peptidase 6
      (SENP6) not being able to bind K399R mutant to desumoylate K166 and K171 in
      Sertoli cells, whereas it can bind RARA with intact K399. On the other hand,
      functional K166 and K171 sites for sumoylation were required for a full
      transcriptional activity, when K399 was intact. These results together suggest
      that both K166 and K171 sumoylation and desumoylation are critical for optimal
      RARA function.

PMID- 19850745
TI  - Adiponectin deficiency, diastolic dysfunction, and diastolic heart failure.
AB  - Aldosterone infusion results in left ventricular hypertrophy (LVH) and
      hypertension and may involve profibrotic and proinflammatory mechanisms. In turn,
      hypertension is the major cause of diastolic heart failure (HF). Adiponectin, an
      adipose-derived plasma protein, exerts antiinflammatory and anti-hypertrophic
      effects and is implicated in the development of hypertension and systolic HF. We
      thus tested the hypothesis that hypoadiponectinemia in aldosterone-induced
      hypertension exacerbated cardiac remodeling and diastolic HF. Wild-type (WT) or
      adiponectin-deficient (APNKO) mice underwent saline or aldosterone infusion and
      uninephrectomy and were fed 1% salt water for 4 wk. Blood pressure was increased
      in aldosterone-infused WT (132 +/- 2 vs. 109 +/- 3 mm Hg; P < 0.01) and further
      augmented in APNKO mice (140 +/- 3 mm Hg; P < 0.05 vs. aldosterone-infused WT).
      LVH was increased in aldosterone-infused WT vs. WT mice (LV/body weight ratio,
      4.8 +/- 0.2 vs. 4.1 +/- 0.2 mg/g) and further increased in aldosterone-infused
      APNKO mice (LV/body weight ratio, 6.0 +/- 0.4 mg/g). Left ventricular ejection
      fraction was not decreased in either aldosterone-infused WT or APNKO hearts.
      Pulmonary congestion however was worse in APNKO mice (P < 0.01). The ratio of
      early ventricular filling over late ventricular filling (E/A) and the ratio of
      mitral peak velocity of early filling to early diastolic mitral annular velocity
      (E/e'), measures of diastolic function, were increased in aldosterone-infused WT
      hearts and further increased in APNKO hearts (P < 0.05 for both). Renal function
      and cardiac fibrosis were no different between both aldosterone-infused groups.
      Aldosterone increased matrix metalloproteinase-2 expression in WT hearts (P <
      0.05 vs. WT and P < 0.01 vs. APNKO). Myocardial atrial natriuretic peptide,
      interferon-gamma, and TNF-alpha expression were increased in aldosterone-infused
      WT hearts. Expression of these proteins was further increased in aldosterone
      infused APNKO hearts. Therefore, hypoadiponectinemia in hypertension-induced
      diastolic HF exacerbates LVH, diastolic dysfunction, and diastolic HF. Whether or
      not adiponectin replacement prevents the progression to diastolic HF will warrant
      further study.

PMID- 19850747
TI  - Peaceful coexistence or clonal dominance?

PMID- 19850748
TI  - CLL: promiscuity leads to risks.

PMID- 19850746
TI  - Robust up-regulation of nuclear red fluorescent-tagged fos marks neuronal
      activation in green fluorescent vasopressin neurons after osmotic stimulation in
      a double-transgenic rat.
AB  - The up-regulation in the expression of mRNA or protein encoded by the c-fos gene
      is widely used as a marker of neuronal activation elicited by various stimuli. To
      facilitate the detection of activated neurons, we generated transgenic rats
      expressing a fusion gene consisting of c-fos coding sequences in frame with
      monomeric red fluorescent protein 1 (mRFP1) under the control of c-fos gene
      regulatory sequences (c-fos-mRFP1 rats). In c-fos-mRFP1 transgenic rats, 90 min
      after hypertonic saline ip administration, nuclear mRFP1 fluorescence was
      observed abundantly in brain regions known to be osmosensitive, namely the median
      preoptic nucleus, organum vasculosum lamina terminalis, supraoptic nucleus,
      paraventricular nucleus, and subfornical organ. Immunohistochemistry for Fos
      protein confirmed that the distribution of Fos-like immunoreactivity in
      nontransgenic rats was similar to those of mRFP1 fluorescence after ip
      administration of hypertonic saline in the transgenic rats. Several double
      transgenic rats were obtained from matings between transgenic rats expressing an
      arginine vasopressin-enhanced green fluorescent protein fusion gene (AVP-eGFP
      rats) and c-fos-mRFP1 rats. In these double-transgenic rats, almost all eGFP
      neurons in the supraoptic nucleus and PVN expressed nuclear mRFP1 fluorescence 90
      min after hypertonic saline administration. The c-fos-mRFP1 rats are a powerful
      tool that enables the facile identification of activated neurons in the nervous
      system. Furthermore, when combined with transgenes expressing another fluorophore
      under the control of cell-specific regulatory sequences, activation of specific
      neuronal cell types in response to physiological cues can be readily detected.

PMID- 19850749
TI  - Transfused B19V: B-nign, B-ware, B-gone?

PMID- 19850750
TI  - New GATA1 mutation in codon 2 leads to the earliest known premature stop codon in
      transient myeloproliferative disorder.

PMID- 19850751
TI  - Limited efficacy of imatinib in severe pulmonary chronic graft-versus-host
      disease.

PMID- 19850753
TI  - Evaluation of linguistic features useful in extraction of interactions from
      PubMed; application to annotating known, high-throughput and predicted
      interactions in I2D.
AB  - MOTIVATION: Identification and characterization of protein-protein interactions
      (PPIs) is one of the key aims in biological research. While previous research in
      text mining has made substantial progress in automatic PPI detection from
      literature, the need to improve the precision and recall of the process remains.
      More accurate PPI detection will also improve the ability to extract experimental
      data related to PPIs and provide multiple evidence for each interaction. RESULTS:
      We developed an interaction detection method and explored the usefulness of
      various features in automatically identifying PPIs in text. The results show that
      our approach outperforms other systems using the AImed dataset. In the tests
      where our system achieves better precision with reduced recall, we discuss
      possible approaches for improvement. In addition to test datasets, we evaluated
      the performance on interactions from five human-curated databases-BIND, DIP,
      HPRD, IntAct and MINT-where our system consistently identified evidence for
      approximately 60% of interactions when both proteins appear in at least one
      sentence in the PubMed abstract. We then applied the system to extract articles
      from PubMed to annotate known, high-throughput and interologous interactions in
      I(2)D. AVAILABILITY: The data and software are available at:
      http://www.cs.utoronto.ca/ approximately juris/data/BI09/.

PMID- 19850754
TI  - The gputools package enables GPU computing in R.
AB  - MOTIVATION: By default, the R statistical environment does not make use of
      parallelism. Researchers may resort to expensive solutions such as cluster
      hardware for large analysis tasks. Graphics processing units (GPUs) provide an
      inexpensive and computationally powerful alternative. Using R and the CUDA
      toolkit from Nvidia, we have implemented several functions commonly used in
      microarray gene expression analysis for GPU-equipped computers. RESULTS: R users
      can take advantage of the better performance provided by an Nvidia GPU.
      AVAILABILITY: The package is available from CRAN, the R project's repository of
      packages, at http://cran.r-project.org/web/packages/gputools More information
      about our gputools R package is available at
      http://brainarray.mbni.med.umich.edu/brainarray/Rgpgpu

PMID- 19850755
TI  - Identification of non-Hodgkin's lymphoma prognosis signatures using the CTGDR
      method.
AB  - MOTIVATION: Although NHL (non-Hodgkin's lymphoma) is the fifth leading cause of
      cancer incidence and mortality in the USA, it remains poorly understood and is
      largely incurable. Biomedical studies have shown that genomic variations,
      measured with SNPs (single nucleotide polymorphisms) in genes, may have
      independent predictive power for disease-free survival in NHL patients beyond
      clinical measurements. RESULTS: We apply the CTGDR (clustering threshold gradient
      directed regularization) method to genetic association studies using SNPs,
      analyze data from an association study of NHL and identify prognosis signatures
      to diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), the two
      most common subtypes of NHL. With the CTGDR method, we are able to account for
      the joint effects of multiple genes/SNPs, whereas most existing studies are
      single-marker based. In addition, we are able to account for the 'gene and SNP
      within-gene' hierarchical structure and identify not only predictive genes but
      also predictive SNPs within identified genes. In contrast, existing studies are
      limited to either gene or SNP identification, but not both. We propose using
      resampling methods to evaluate the predictive power and reproducibility of
      identified genes and SNPs. Simulation study and data analysis suggest
      satisfactory performance of the CTGDR method.

PMID- 19850756
TI  - Ancestors 1.0: a web server for ancestral sequence reconstruction.
AB  - SUMMARY: The computational inference of ancestral genomes consists of five
      difficult steps: identifying syntenic regions, inferring ancestral arrangement of
      syntenic regions, aligning multiple sequences, reconstructing the insertion and
      deletion history and finally inferring substitutions. Each of these steps have
      received lot of attention in the past years. However, there currently exists no
      framework that integrates all of the different steps in an easy workflow. Here,
      we introduce Ancestors 1.0, a web server allowing one to easily and quickly
      perform the last three steps of the ancestral genome reconstruction procedure. It
      implements several alignment algorithms, an indel maximum likelihood solver and a
      context-dependent maximum likelihood substitution inference algorithm. The
      results presented by the server include the posterior probabilities for the last
      two steps of the ancestral genome reconstruction and the expected error rate of
      each ancestral base prediction. AVAILABILITY: The Ancestors 1.0 is available at
      http://ancestors.bioinfo.uqam.ca/ancestorWeb/.

PMID- 19850757
TI  - Seed-based INTARNA prediction combined with GFP-reporter system identifies mRNA
      targets of the small RNA Yfr1.
AB  - MOTIVATION: Prochlorococcus possesses the smallest genome of all sequenced
      photoautotrophs. Although the number of regulatory proteins in the genome is very
      small, the relative number of small regulatory RNAs is comparable with that of
      other bacteria. The compact genome size of Prochlorococcus offers an ideal system
      to search for targets of small RNAs (sRNAs) and to refine existing target
      prediction algorithms. RESULTS: Target predictions for the cyanobacterial sRNA
      Yfr1 were carried out with INTARNA in Prochlorococcus MED4. The ultraconserved
      Yfr1 sequence motif was defined as the putative interaction seed. To study the
      impact of Yfr1 on its predicted mRNA targets, a reporter system based on green
      fluorescent protein (GFP) was applied. We show that Yfr1 inhibits the translation
      of two predicted targets. We used mutation analysis to confirm that Yfr1 directly
      regulates its targets by an antisense interaction sequestering the ribosome
      binding site, and to assess the importance of interaction site accessibility.

PMID- 19850759
TI  - John Bryant takes a closer look at some of this month's original articles.

PMID- 19850760
TI  - Diffusely abnormal white matter in progressive multiple sclerosis: in vivo
      quantitative MR imaging characterization and comparison between disease types.
AB  - BACKGROUND AND PURPOSE: Recent postmortem studies in MS brain suggest that the
      severity of changes in DAWM can be measured by using quantitative MR imaging.
      This study aimed to characterize DAWM in vivo by using 4 quantitative MR imaging
      measures and to explore differences between MS disease types. MATERIALS AND
      METHODS: In 17 patients with chronic MS (7 PP, 10 SP), quantitative MR imaging
      was performed at 1.5T, yielding whole-brain voxelwise maps of T1, MTR, ADC, and
      FA. ROIs were placed to obtain values for DAWM, NAWM, and WM lesions. A general
      linear mixed-model analysis was used to compare T1, MTR, ADC, and FA between
      tissue types and disease types. RESULTS: Values of T1, MTR, ADC, and FA for DAWM
      were intermediate to those observed in NAWM and WM lesions. In patients with
      SPMS, DAWM was significantly different from both WM lesions and NAWM regarding
      all 4 measures, while in patients with PPMS, DAWM differed significantly from
      NAWM regarding T1, MTR, and FA and from lesions only regarding FA. Most
      interesting, DAWM differed between disease types: DAWM in patients with SPMS
      exhibited significantly higher T1 and lower MTR than did DAWM in patients with
      PPMS. CONCLUSIONS: In vivo T1, MTR, ADC, and FA reflect the variable severity of
      pathologic changes in DAWM in MS. Moreover, these quantitative MR imaging
      measures suggest that DAWM may differ between PPMS and SPMS.

PMID- 19850761
TI  - 3D C-arm conebeam CT angiography as an adjunct in the precise anatomic
      characterization of spinal dural arteriovenous fistulas.
AB  - BACKGROUND AND PURPOSE: Precise anatomic understanding of the vascular anatomy of
      SDAVFs is required before treatment. This study demonstrates the utility of C-arm
      conebeam CT to locate precisely the fistulous point in SDAVFs and the courses of
      their feeding arteries and draining veins. MATERIALS AND METHODS: This
      retrospective study reports 14 consecutive patients with SDAVFs who underwent DSA
      and C-arm conebeam CT angiography. SDAVF sites included 5 thoracic, 7 lumbar, and
      2 sacral fistulas. Selective DSA initially identified the location and arterial
      supply of the SDAVF. C-arm conebeam CT angiography was then performed with
      selective injection into the feeding artery. Reconstructed images were reviewed
      at a workstation with the referring surgeon, in conjunction with the standard 2D
      DSA images. The value of C-arm conebeam CT in depicting the fistula and the
      relationship to adjacent structures was qualitatively assessed. RESULTS: In all
      14 patients, C-arm conebeam CT angiography was technically successful and
      precisely demonstrated the site of the fistula, feeding arteries, draining veins,
      and the relationship of the fistula to adjacent osseous structures. Information
      obtained from the C-arm conebeam CT angiogram was considered useful in all
      surgically (12 patients) and endovascularly (2 patients) treated SDAVFs.
      CONCLUSIONS: 3D C-arm conebeam CT angiography is a useful adjunct to 2D DSA in
      the anatomic characterization of SDAVFs. The technique allowed improved
      visualization of the vascular anatomy of the SDAVFs and clearer definition of
      their spatial relationships to adjacent structures.

PMID- 19850762
TI  - Diffusion tensor MR imaging in children with pantothenate kinase-associated
      neurodegeneration with brain iron accumulation and their siblings.
AB  - BACKGROUND AND PURPOSE: It has been reported that iron concentration influences
      DTI metrics in deep gray matter nuclei. We hypothesized that increased FA in the
      deep gray nuclei may indicate abnormal iron accumulation in patients with PKAN
      and their siblings. MATERIALS AND METHODS: Seven patients with the characteristic
      "eye-of-the-tiger sign," their 5 siblings, and 5 age-matched controls were
      prospectively studied. One-way ANOVA with Bonferroni post hoc multiple
      comparisons was used to compare DTI metrics (FA and MD) among subject groups in
      the putamen, CN, GP, SN, and ALIC. In addition, hypointense and hyperintense
      regions of the eye-of-the-tiger sign were segmented, and their DTI metrics were
      compared. In the patient group, the values of DTI metrics in hypointense regions
      were also compared with those of the ALIC. RESULTS: A significant increase in FA
      values of the GP and SN from controls to the patient group to siblings was
      observed. In the GP, MD values were significantly higher in patients compared
      with controls and siblings. The patients showed significantly increased FA with
      decreased MD in hypointense compared with hyperintense regions of the eye-of-the
      tiger sign. No difference in FA values were observed between the ALIC and
      hypointense regions of the eye-of-the-tiger sign in patients. CONCLUSIONS: High
      FA values in siblings of patients with PKAN suggest the presence of abnormal iron
      in deep gray matter nuclei, even in the absence of its demonstration on T2*
      weighted GRE.

PMID- 19850763
TI  - Tract-based analysis of callosal, projection, and association pathways in
      pediatric patients with multiple sclerosis: a preliminary study.
AB  - BACKGROUND AND PURPOSE: Region-of-interest (ROI) and tract-based diffusion tensor
      imaging (DTI) analyses have detected increased apparent diffusion coefficients
      (ADCs) and decreased fractional anisotropy (FA) in callosal and projection
      systems of adult patients with multiple sclerosis (MS). We explored whether
      similar changes occur in pediatric patients with MS, assessing 3 major white
      matter pathways (interhemispheric, projection, and intrahemispheric) in both
      visibly involved and normal-appearing white matter (NAWM). MATERIALS AND METHODS:
      DTI datasets from 10 patients with established pediatric MS and 10 age- sex-, and
      imaging technique-matched controls were analyzed. Tracts were reconstructed by
      using a fiber assignment by continuous tracking algorithm with a diffusion
      weighted imaging mask and a 35 degrees angular threshold. Tracts were selected by
      using standard ROI placements on color FA maps cross-referenced to b = 0 T2
      weighted images for studying white matter pathways. Ten identical ROIs were
      placed in NAWM on b = 0 T2-weighted images to ensure that both ROIs and resulting
      tracts passed through NAWM. RESULTS: In pediatric MS, all tracts had higher mean
      ADC values (P = .002 to P < .04) and lower mean FA (P = .009 to P < .02) than
      those in healthy controls. Even when the tracts were confined to NAWM, the mean
      ADC was higher (P < .004 to P < .05) and the mean FA was lower (P = .002 to P <
      .02). T2 lesion burden correlated with tract-based mean ADC. ROI mean ADC
      increased, and both tract and ROI mean FA decreased with increasing T2 lesion
      burden, however with a statistically nonsignificant correlation. CONCLUSIONS:
      Increased mean ADC and decreased mean FA occur in all 3 major white matter
      pathways, both in visibly involved white matter and NAWM in pediatric MS.

PMID- 19850764
TI  - Protected endovascular revascularization of subacute and chronic total occlusion
      of the internal carotid artery.
AB  - BACKGROUND AND PURPOSE: The natural course of symptomatic carotid artery
      occlusion with hemodynamic impairment is poor. Surgical revascularization may
      improve the outcome; however, its efficacy has not been established yet. The goal
      of this study was to characterize the technical and clinical outcomes following
      endovascular recanalization of the ICA under cerebral circulatory protection.
      MATERIALS AND METHODS: Endovascular recanalization was attempted in 8 patients
      with symptomatic ICA occlusions. The duration of the occlusion ranged from 7 days
      to 7 months (mean, 2.5 months), and the mean length of the occlusion was 95 mm.
      Cerebral hemodynamics ipsilateral to the side of the occlusion were severely
      impaired in all patients. The endovascular procedure was performed under total
      cerebral circulatory protection, beginning with proximal protection with a
      subsequent switch to distal protection after successful guidewire passage.
      RESULTS: The occlusion was recanalized successfully in 7 of 8 patients (88%),
      resulting in improvement of ipsilateral cerebral hemodynamics without symptomatic
      stroke. Small asymptomatic ischemic lesions were detected in 6 of 8 patients
      (75%) on DWI, and 1 patient developed a mild groin hematoma. Ischemic episodes
      did not recur during the mean follow-up period of 19 months. However, 1 patient
      experienced asymptomatic reocclusion, which was re-treated successfully without
      complications, while another patient developed mild retinal hemorrhage at 3
      months after the procedure due to the combination of antiplatelet and
      anticoagulant therapy. CONCLUSIONS: Endovascular revascularization of an ICA
      occlusion is feasible and well-tolerated in patients with subacute or chronic
      total occlusion of the ICA.

PMID- 19850765
TI  - Candidate biomarkers of extravascular extracellular space: a direct comparison of
      apparent diffusion coefficient and dynamic contrast-enhanced MR imaging--derived
      measurement of the volume of the extravascular extracellular space in
      glioblastoma multiforme.
AB  - BACKGROUND AND PURPOSE: ADC measurements have been shown to have an inverse
      relationship with tumor cell density. DCE-MR imaging modeling techniques can
      produce a measurement of the v(e), which would also be expected to have an
      inverse relationship with cell density. The objective of this study was to test
      the hypothesis that areas of increased cellularity, and therefore low ADC, would
      be expected to have a small EES (low v(e)). MATERIALS AND METHODS: Nineteen
      patients with GBM were recruited. All imaging was performed before surgery on a
      3T MR imaging scanner. Imaging included diffusion tensor imaging, T1-weighted DCE
      MR imaging, and anatomic sequences. Tumor VOIs were defined on the anatomic
      images and modified to contain only enhancing voxels. Parametric maps of ADC and
      v(e) were generated. Statistical analysis of ADC and v(e) was performed on both a
      voxel-by-voxel basis and comparison of median values. RESULTS: No correlation was
      demonstrated between ADC and v(e) in either a voxel-by-voxel analysis or
      comparison of median values (P = .124). CONCLUSIONS: This study failed to
      demonstrate a correlation between ADC and v(e). This is important because it
      suggests that though the mechanisms underlying these parameters are theoretically
      similar, they actually reflect different aspects of tumor microenvironment.
      Consequently ADC and v(e) should be considered to provide independent information
      about the properties of the EES.

PMID- 19850766
TI  - Assessment of vascular supply of hypervascular extra-axial brain tumors with 3T
      MR regional perfusion imaging.
AB  - BACKGROUND AND PURPOSE: The vascular supply of extra-axial brain tumors provided
      by the external carotid artery has not been studied with RPI. The purpose of this
      work was to determine whether RPI assessment is feasible and provides information
      on the vascular supply of hypervascular extra-axial brain tumors. MATERIALS AND
      METHODS: Conventional ASL and RPI studies were performed at 3T in 8 consecutive
      patients with meningioma. On the basis of MRA results, we performed RPI by
      placing a selective labeling slab over the external carotid artery. Five patients
      underwent DSA before surgery. Two neuroradiologists independently evaluated the
      overall image quality, the degree of tumor perfusion, and the extent of the tumor
      vascular territory on conventional ASL and RPI. RESULTS: In overall quality of
      conventional ASL and RPI, no images interfered with interpretation. In
      comparisons of the vascular tumor territory identified by the conventional ASL
      and RPI techniques, the territories coincided in 3 cases, were partially
      different in 4, and completely different in 1. The interobserver agreement was
      very good (kappa = 0.82). In 5 patients who underwent DSA, the 4 patients in whom
      the dominant supply was the external carotid artery were scored as coincided or
      partially different. The 1 patient in whom the vascular supply was from the
      internal carotid artery was scored as completely different. CONCLUSIONS: RPI with
      selective labeling of the external carotid artery is feasible and may provide
      information about the vascular supply of hypervascular extra-axial brain tumors.

PMID- 19850767
TI  - Acute hydrocephalus and cerebral perfusion after aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Acute hydrocephalus after aneurysmal subarachnoid
      hemorrhage (SAH) may decrease cerebral perfusion by increasing intracranial
      pressure. We studied cerebral perfusion in patients with and without acute
      hydrocephalus after SAH. MATERIALS AND METHODS: We performed noncontrast CT
      scans, CT perfusion (CTP), and CT angiography on admission in all patients with
      aneurysmal SAH. Patients were dichotomized at a relative bicaudate index of 1 for
      the presence or absence of hydrocephalus. Cerebral perfusion was measured in the
      cortex, basal ganglia, and periventricular white matter. Mean CTP parameters were
      compared between patients with and without acute hydrocephalus (ie, within 3 days
      after SAH). RESULTS: We included 138 consecutive patients with successful CTP
      measurements, of whom 49 (36%) had acute hydrocephalus. Mean cerebral blood flow
      (CBF) was lower in patients with hydrocephalus than in those without in the basal
      ganglia (difference of means, 6.8; 95% CI, 1.6-11.0 mL/100 g/min) and
      periventricular white matter (difference of means, 3.8; 95% CI, 0.9-6.8 mL/100
      g/min) but not in the cortex (difference of means, 1.8; 95% CI, -2.8 to 6.4
      mL/100 g/min). In all regions studied, mean transit time (MTT) and time-to-peak
      (TTP) were statistically significantly longer in patients with hydrocephalus, but
      cerebral blood volume (CBV) values were similar. CONCLUSIONS: Acute hydrocephalus
      after SAH reduces CBF in the deep gray matter and periventricular white matter
      and delays MTT and TTP in all investigated brain areas. The negative effect of
      acute hydrocephalus on cerebral perfusion in patients with SAH seems more
      pronounced in the vicinity of the ventricles than in remote sites.

PMID- 19850768
TI  - Superficial siderosis in cerebral amyloid angiopathy.

PMID- 19850769
TI  - Caveats for scientific publication in the modern marketplace.

PMID- 19850770
TI  - Kidney transplantation in the context of renal replacement therapy.
AB  - Kidney transplantation has dramatically evolved from a life-saving yet unproven
      therapy for patients with renal failure to a mature field that is the preferred
      treatment for those suffering from ESRD. Patients who receive a transplant
      experience a 68% lower risk of death compared with those waiting on dialysis for
      a transplant. This benefit is afforded to all patient subgroups including the
      elderly (> or =70 yr), and diabetics, who can gain 11 yr of extra life with
      transplantation. Prolonged transplant wait times result in a higher risk of death
      but this can be ameliorated with preemptive transplantation. Future challenges
      will focus on appropriate organ allocation and addressing long-term renal
      function and comorbid conditions so patients can enjoy the full benefits of
      transplantation.

PMID- 19850771
TI  - Chronic calcineurin inhibitor nephrotoxicity: reflections on an evolving
      paradigm.
AB  - Use of the calcineurin inhibitors (CNI) cyclosporine and tacrolimus has
      revolutionized solid organ transplantation. For more than 30 yr, the transplant
      community has dealt with nephrotoxicity attributed to these agents. Acute renal
      vasoconstriction (as described by many investigators, including John Curtis and
      colleagues) is the unequivocal consequence of their use; chronic CNI nephropathy,
      although indistinct in terms of histology and pathophysiology, has become
      accepted as a major cause of late kidney allograft failure. This article examines
      clinical, laboratory, and histologic findings that evolved into a paradigm that
      was never fully consistent with observed outcomes and new evidence that may offer
      an alternative interpretation for adverse events that are attributed to CNI
      nephrotoxicity in kidney transplant recipients.

PMID- 19850772
TI  - Dystroglycan in the molecular diagnosis of the podocytopathies.

PMID- 19850773
TI  - Mouse and human induced pluripotent stem cells as a source for multipotent Isl1+
      cardiovascular progenitors.
AB  - Ectopic expression of defined sets of genetic factors can reprogram somatic cells
      to create induced pluripotent stem (iPS) cells. The capacity to direct human iPS
      cells to specific differentiated lineages and to their progenitor populations can
      be used for disease modeling, drug discovery, and eventually autologous cell
      replacement therapies. During mouse cardiogenesis, the major lineages of the
      mature heart, cardiomyocytes, smooth muscle cells, and endothelial cells arise
      from a common, multipotent cardiovascular progenitor expressing the transcription
      factors Isl1 and Nkx2.5. Here we show, using genetic fate-mapping, that Isl1(+)
      multipotent cardiovascular progenitors can be generated from mouse iPS cells and
      spontaneously differentiate in all 3 cardiovascular lineages in vivo without
      teratoma. Moreover, we report the identification of human iPS-derived ISL1(+)
      progenitors with similar developmental potential. These results support the
      possibility to use patient-specific iPS-generated cardiovascular progenitors as a
      model to elucidate the pathogenesis of congenital and acquired forms of heart
      diseases.-Moretti, A., Bellin, M., Jung, C. B., Thies, T.-M., Takashima, Y.,
      Bernshausen, A., Schiemann, M., Fischer, S., Moosmang, S., Smith, A. G., Lam, J.
      T., Laugwitz, K.-L. Mouse and human induced pluripotent stem cells as a source
      for multipotent Isl1(+) cardiovascular progenitors.

PMID- 19850775
TI  - FDA approves pralatrexate for treatment of rare lymphoma.

PMID- 19850776
TI  - With Maine on board, pharmacists in all 50 states can vaccinate: H1N1 prompts
      emergency vaccination rules for pharmacists.

PMID- 19850777
TI  - NQF endorses medication management measures.

PMID- 19850778
TI  - International meeting focuses on pharmacists' education, responsibility.

PMID- 19850779
TI  - Interaction between liquid protein solution and omeprazole suspension.

PMID- 19850780
TI  - Effect of a Web-based continuing-education program on pharmacist learning.

PMID- 19850781
TI  - Generic substitution of antiepileptic medications in patients with epilepsy: is
      this a potential problem?

PMID- 19850782
TI  - Benefits of a teaching certificate program for pharmacy residents.

PMID- 19850783
TI  - Use of a tablet personal computer to enhance patient care on multidisciplinary
      rounds.

PMID- 19850784
TI  - Arsenic trioxide as first-line treatment for acute promyelocytic leukemia.
AB  - PURPOSE: The history, clinical pharmacology and toxicities, and role of arsenic
      trioxide as a first-line agent for treating acute promyelocytic leukemia (APL)
      are described. SUMMARY: APL is most often characterized by the hallmark
      reciprocal translocation between chromosomes 15 and 17, leading to the fusion of
      the promyelocytic gene and retinoic acid receptor alpha. Arsenic's therapeutic
      utility as an antileukemic agent was first described in the late 18th century.
      Arsenic trioxide demonstrates a dual, dose-dependent mechanism of action and can
      induce both partial myeloid differentiation and apoptosis. Arsenic trioxide is
      generally well tolerated, with reversible toxicities rarely requiring
      discontinuation of therapy. Toxicities associated with arsenic trioxide include
      leukocytosis, Q-T interval prolongation, APL differentiation syndrome, and
      hepatotoxicity. Since 2000, arsenic trioxide has been used as the standard of
      care for relapsed APL, with remission rates greater than 80% as a single agent.
      In an attempt to maximize disease-free survival and minimize relapse rates in
      patients with APL, arsenic trioxide is now being investigated as first-line
      therapy in the management of APL, with several studies showing promising
      outcomes. When used alone or in combination with tretinoin, the rates of complete
      remission have exceeded 85%, with high rates of molecular remission. CONCLUSION:
      Arsenic trioxide, alone or in combination with tretinoin, as first-line therapy
      in newly diagnosed APL has resulted in high rates of complete remission and
      molecular remission. Arsenic trioxide combined with tretinoin has shortened the
      time to achieve complete remission and lengthened disease-free survival, findings
      that suggest the usefulness of the regimen as first-line treatment for APL.

PMID- 19850785
TI  - Probable nitrofurantoin-induced bronchiolitis obliterans with organizing
      pneumonia.
AB  - PURPOSE: A case of bronchiolitis obliterans with organizing pneumonia (BOOP) that
      developed after three years of nitrofurantoin therapy is described. SUMMARY: An
      89 year-old Caucasian woman weighing 60 kg with diastolic heart failure and a
      history of urosepsis, viral pericarditis, and atrial fibrillation arrived at the
      emergency department with worsening dyspnea, shortness of breath that had limited
      her activities of daily living for three days, and lower extremity edema. Over
      the previous six months the patient had experienced decreased appetite, abdominal
      bloating, and a 9.1-kg weight loss. Four months prior, the primary physician
      diagnosed her symptoms of worsening dyspnea at rest and with exertion as severe
      bronchitis. Imaging at the time of presentation revealed interstitial fibrosis
      consistent with nitrofurantoin-induced BOOP. A diagnosis of BOOP was made,
      nitrofurantoin was discontinued, and the patient was discharged home on oxygen.
      Prednisone 20 mg was started two weeks later, after no improvement in symptoms
      was seen. Seven weeks after nitrofurantoin discontinuation, the results of a
      chest radiograph and computed tomography scan were unchanged, but her symptoms
      had improved by 20%. The patient was readmitted three weeks later for worsening
      dyspnea, and it was determined that prednisone had resulted in fluid retention,
      complicating her diastolic congestive heart failure. Prednisone therapy was
      therefore tapered off after two months of treatment. No improvement in subjective
      symptoms, in chest radiograph results, or in BOOP symptoms was seen after three
      months of prednisone discontinuation and five months of nitrofurantoin
      discontinuation. CONCLUSION: An 89-year-old woman developed unresolving BOOP
      after three years of nitrofurantoin therapy.

PMID- 19850786
TI  - Bioequivalence among three methods of administering pantoprazole granules in
      healthy subjects.
AB  - PURPOSE: The bioequivalence among three methods of administering pantoprazole
      granules was studied in healthy subjects. METHODS: In this randomized, open
      label, three-period, crossover study, 25 healthy adults received a single 40-mg
      dose of pantoprazole granules with applesauce orally, with apple juice orally,
      and with apple juice administered via a nasogastric tube. Subjects were randomly
      assigned to one of six treatment sequences. Blood samples were collected within 2
      hours before treatment administration on study day 1 and at 0.33, 0.5, 1, 1.5, 2,
      2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours after treatment administration.
      Plasma pantoprazole concentrations were analyzed by a validated liquid
      chromatography-tandem mass spectrometry method. The plasma pantoprazole
      concentration-time data for each subject were analyzed using noncompartmental
      methods. The 90% confidence intervals (CIs) for the test:reference geometric mean
      ratio were calculated for the peak pantoprazole concentration (C(max) ) and area
      under the concentration-time curve (AUC). RESULTS: Of the 25 subjects enrolled,
      100% completed the study. The mean C(max) and AUC values were similar for the
      three administration methods. The 90% CIs for the ratios of the geometric means
      of the granules in apple juice orally (92.4-112.5%) and in apple juice
      administered through a nasogastric tube (102.7-125.2%), relative to the granules
      administered with applesauce orally, were essentially within the bioequivalent
      limits of 80-125%. No serious adverse events or study discontinuations occurred.
      CONCLUSION: Three methods of administering pantoprazole delayed-release granules
      for oral suspension-with apple juice orally, with applesauce orally, and with
      apple juice through a nasogastric tube--were bioequivalent in healthy subjects.

PMID- 19850788
TI  - Use of pharmacy informatics resources by clinical pharmacy services in acute care
      hospitals.
AB  - PURPOSE: The use of pharmacy informatics resources by clinical pharmacy services
      and the presence of a pharmacy informatics specialist in acute care hospitals
      were evaluated. METHODS: Two hundred randomly selected pharmacies in general
      medical and surgical hospitals in the United States with at least 100 acute care
      beds were surveyed via mail. Survey items gathered information regarding facility
      attributes, opinions about staff pharmacists' understanding of information
      technology, and departmental utilization of pharmacy informatics. RESULTS: Of the
      200 surveys mailed, 114 (57%) were returned completed. When asked to rate their
      departments' use of pharmacy informatics, 82% indicated that pharmacy informatics
      use was good or fair, while 12% considered information use to be optimized. A
      majority of respondents (60%) indicated that a pharmacy informatics specialist
      was employed within the pharmacy, with 47% indicating that the specialist was a
      pharmacist. An overwhelming percentage of these pharmacists received informatics
      training on the job, and roughly half had specialty positions integrated into
      their pharmacist job description. No significant association existed between the
      use of pharmacy informatics and facility teaching status (teaching versus
      nonteaching), geographic location (urban versus rural), or use of computerized
      prescriber order entry. Employment of a pharmacy informatics specialist was
      significantly associated with the use of such informatics applications as
      database mining, renal-dosing-rules engines, antibiotic-pathogen matching-rules
      engines, and pharmacokinetic-monitoring rules engines. CONCLUSION: The use of
      clinical pharmacy informatics in patient care in acute care hospitals with at
      least 100 beds was significantly more likely when a pharmacy informatics
      specialist was present in the pharmacy. However, 4 in 10 hospital pharmacies did
      not employ a pharmacy informatics specialist.

PMID- 19850787
TI  - Physicochemical stability of oxaliplatin in 5% dextrose injection stored in
      polyvinyl chloride, polyethylene, and polypropylene infusion bags.
AB  - PURPOSE: The physicochemical stability of extemporaneous dilutions of oxaliplatin
      in 5% dextrose injection stored in polyvinyl chloride (PVC), polypropylene, and
      polyethylene infusion bags was studied. METHODS: Oxaliplatin 100 mg/20 mL
      concentrated solution was diluted in 100 mL of 5% dextrose injection in PVC,
      polypropylene, and polyethylene infusion bags to produce nominal oxaliplatin
      concentrations of 0.2 and 1.3 mg/mL. The filled bags were stored for 14 days at
      20 degrees C and protected from light, at 20 degrees C under normal fluorescent
      light, and at 4 degrees C. A 1-mL sample was removed from each bag at time 0 and
      at 24, 48, 72, 120, 168, and 336 hours. The samples were visually inspected for
      color and clarity, and the pH values of the solutions were measured. High
      performance liquid chromatography was used to assay oxaliplatin concentration.
      Bacterial contamination was assessed on study day 14 after incubation in
      trypticase soy solution for three days at 37 degrees C. RESULTS: Solutions of
      oxaliplatin 0.2 and 1.3 mg/mL in 5% dextrose injection were stable in the three
      container types for at least 14 days at both 4 degrees C and 20 degrees C without
      regard to light exposure. No color change was detected during the storage period,
      and pH values remained stable. No microbial contamination was detected in any
      samples over the study period. CONCLUSION: Oxaliplatin solutions diluted in 5%
      dextrose injection to 0.2 and 1.3 mg/mL were stable in PVC and PVC-free infusion
      bags for at least 14 days at both 4 degrees C and 20 degrees C without regard to
      light exposure.

PMID- 19850789
TI  - Implementation of home-based medication order entry at a community hospital.
AB  - PURPOSE: The implementation of a home-based order-entry program at a community
      hospital is described. SUMMARY: Parkview Hospital is a 600-bed, community-based
      facility located in Fort Wayne, Indiana, that provides 24-hour pharmacy services.
      The main purpose for establishing a home-based order-entry program was to provide
      extra pharmacist coverage during the event of a spontaneous order surge in an
      effort to maintain excellent customer service. A virtual private network (VPN)
      was created to ensure the security and confidentiality of patients' health care
      information. The names of volunteer pharmacists who met specific criteria and who
      were capable of performing home-based order entry were collected. These
      pharmacists were trained and tested in the home-based order-entry process. When
      home-based order-entry is needed, the lead pharmacist contacts the pharmacists on
      the list by telephone. If available, the pharmacists (maximum of three) are
      notified to log into the Internet, access the VPN, and perform order entry with
      the same vigilance, confidentiality, and care as they would onsite. Home-based
      order entry is discontinued when off-trigger points are met. Pharmacists entering
      orders from home are paid by the time spent conducting order entry. Pharmacists
      reported that the program was easy to contact home-based order-entry volunteers,
      there were no problems with logging into the VPNs, and turnaround time was close
      to our target of 25 minutes. CONCLUSION: A community-based hospital successfully
      implemented a home-based medication order-entry program. The program alleviated
      the shortage of pharmacists during spontaneous surges of medication orders.

PMID- 19850790
TI  - Implementing a comprehensive, 24-hour emergency department pharmacy program.
AB  - PURPOSE: The implementation of a comprehensive, 24-hour emergency department
      pharmacy program (EDPP) is described. SUMMARY: An EDPP was created at the
      Veterans Affairs San Diego Healthcare System to address deficiencies identified
      by the pharmacy service within the ED, including medication tracking,
      documentation of doses administered, and formulary management. The documentation
      system used in the EDPP, including a computerized spreadsheet and documentation
      cards, allowed the activities of the ED pharmacists to be tracked on a 24-hour
      basis. This type of data collection allowed us to evaluate the impact of the
      program based on the quality of patient care delivered as well as cost. During
      the initial six-month implementation period, the ED pharmacists recorded 9,568
      interventions. The information from these interventions was used to assess the
      safety components and to estimate the cost avoidance of their activities. A staff
      satisfaction survey was also created to assess the pharmacist's impact on
      providers and nurses, as well as its effect on workflow within the ED. Among the
      many benefits realized, the EDPP improved the quality of patient care, decreased
      medication errors and patient wait times, improved the medication reconciliation
      process, enhanced formulary management, ensured prospective medication order
      review, and increased overall patient safety, as evidenced by the documented
      interventions and staff satisfaction survey. The projected cost savings for the
      medical center during the first year of EDPP implementation was calculated as
      $1,691,185. CONCLUSION: A tertiary care teaching hospital successfully
      implemented a 24-hour, comprehensive ED pharmacy service that enhanced the
      efficiency and delivery of patient care and resulted in significant cost savings.

PMID- 19850791
TI  - Homotaurine: a failed drug for Alzheimer's disease and now a nutraceutical for
      memory protection.

PMID- 19850792
TI  - One face behind the numbers.

PMID- 19850793
TI  - USA health reforms and the NHS.

PMID- 19850794
TI  - Prehospital paediatric emergency care: paediatric triage.
AB  - The practice of triage was conceived during the Napoleonic wars, with the aim of
      salvaging those soldiers whose injuries were readily treatable, returning them to
      the battlefield at the earliest opportunity. Literally, the word triage means "to
      sieve" or "to sort" (French trier), and those earlier battlefield principles have
      been refined and expanded to now encompass trauma and medical emergencies, with
      triage practiced in prehospital and hospital settings. To address the anatomical,
      physiological and developmental differences encountered when dealing with
      children, specific paediatric triage systems have also been developed, and this
      article discusses their merits.

PMID- 19850795
TI  - Organisation of traumatic head injury management in the Nordic countries.
AB  - OBJECTIVE: The aim of this study is to map and evaluate the available resources
      and the premises of traumatic head injury management in the Nordic countries,
      before the implementation of a Nordic adaption of the Brain Trauma Foundation
      guidelines for prehospital management. METHODS: The study is a synthesis of two
      cross-sectional surveys. Questionnaires were used to collect data on the annual
      number of acute head injury operations, the infrastructure, the level of
      education, the use of trauma protocols and the management of traumatic head
      injury at Nordic hospitals. RESULTS: The proportion of acute head injury
      operations performed outside a neurosurgical department was 0% in Denmark, 16% in
      Finland, 19% in Norway and 33% in Sweden. Eighty-four per cent of Nordic
      hospitals had written protocols for the assessment and treatment of trauma
      patients and 78% had regular training in trauma management; 67% had specific
      protocols for the treatment of traumatic head injury. Computed tomography (CT)
      was available in 93% of the hospitals, and 59% of the hospitals could link CT
      scans to the regional neurosurgical department. CONCLUSIONS: Most Nordic
      hospitals are well prepared to manage patients with acute traumatic head injury.
      A substantial proportion of the operations are performed at local and central
      hospitals without neurosurgical expertise, despite an efficient pre and
      interhospital transport system. The Nordic adaption of the Brain Trauma
      Foundation guidelines recommends that this practice is terminated.

PMID- 19850796
TI  - Qualitative research: specific designs for qualitative research in emergency
      care?
AB  - This article follows our description of generic qualitative approaches, focusing
      on the specific designs of ethnography, grounded theory and phenomenology.
      Distinguishing features are described, including methodological approaches and
      methods for enhancing rigour. The use of these designs in emergency care is
      unusual but informative, and important work has been produced. Whether used in a
      pure or applied manner, it is likely that such approaches will add to our
      understanding of the emergency world.

PMID- 19850797
TI  - Introduction of the Liverpool Care Pathway for end of life care to emergency
      medicine.
AB  - AIM: To improve the care of patients presenting to the emergency department who
      are acutely dying or those in whom further disease-modifying treatment is not
      appropriate. DESIGN: A quality improvement report on the implementation of a
      modified Liverpool Care Pathway for the Dying Patient (LCP) in an emergency
      medicine department. SETTING: The emergency medicine department of Ninewells
      Hospital, Dundee. Ninewells Hospital is the tertiary referral and teaching
      hospital for the east coast of Scotland and North East Fife. KEY MEASURES FOR
      IMPROVEMENT: The pathway was introduced after a 2001 study and a 2003 audit
      showed that the department had an increasing role in the care of the acutely
      dying, but some inconsistency in approach. Key measures for improvement were to
      improve communication between staff, improve the consistency of care and improve
      the perceived quality of care given. Senior decision making remains a crucial
      element of the pathway. STRATEGIES FOR CHANGE: A modified LCP was developed and
      launched in November 2005. Change was managed via a series of meetings and a
      pilot process. Serial review and audit allowed ongoing quality review of the
      pathway and improvements. RESULTS: The care of the dying patient has become a
      more consistent and positive endeavour. Nursing staff are very satisfied with its
      use, and it is hoped that the LCP pathway can be developed further within the
      organisation. CONCLUSIONS: It has been a rewarding undertaking to improve the
      care of dying patients, but one which has taken time and has required consistent
      management of change to promote the positive outcomes.

PMID- 19850798
TI  - DNW--"did not wait" or "demographic needing work": a study of the profile of
      patients who did not wait to be seen in an Irish emergency department.
AB  - BACKGROUND: Patients who fail to wait for medical assessment in the emergency
      department (ED) have been referred to in the international literature as "did not
      wait" (DNW) or "left without being seen" (LWBS) patients or, indeed, simply as
      "walkouts". This is taken as a performance indicator internationally. In common
      with many countries, Ireland has very considerable problems in the delivery of ED
      care due largely to inadequate resources and the inappropriate use of EDs as
      holding bays for admitted patients. This is the first study of this size to
      profile the DNW phenomenon in Ireland. METHODS: The charts of DNW patients were
      identified and the DNW status was entered into the ED computer record. Data
      concerning age, sex, time of arrival, date of arrival, triage category and
      presenting complaint were recorded. RESULTS: In the study period there were 11
      662 patient attendances, of whom 871 patients (7.47%) did not wait for
      assessment. Triage category was highly statistically significant, with those in
      the lowest triage category having the highest numbers not waiting to be seen
      (p<0.001). Those attending at night (p<0.001) and at the weekend (p = 0.03) were
      most likely to leave without being assessed. CONCLUSION: Failure to provide the
      service in a timely manner gives rise to patients leaving without receiving the
      medical assessment they came to obtain. This is a serious clinical problem and
      puts both those requiring care and those providing it at risk of adverse
      outcomes.

PMID- 19850799
TI  - Magnesium sulphate in the treatment of acute asthma: evaluation of current
      practice in adult emergency departments.
AB  - BACKGROUND: A recent meta-analysis showed that intravenous and nebulised
      magnesium sulphate have similar levels of evidence to support their use in the
      treatment of acute asthma in adults. This consisted of weak evidence of effect on
      respiratory function and hospital admissions, with wide confidence intervals
      ranging from no effect to significant positive effects. Current BTS/SIGN
      guidelines suggest an equivocal role for intravenous magnesium sulphate and no
      role for nebulised magnesium sulphate. A study was performed to assess what
      emergency physicians currently do in their management of acute asthma. METHOD: A
      postal survey was undertaken of all adult emergency departments within the UK. A
      structured questionnaire was sent to all clinical leads in emergency medicine
      about their current usage of both intravenous and nebulised magnesium sulphate in
      the treatment of acute asthma. RESULTS: 180 of the 251 emergency departments in
      the UK responded (72%). Magnesium sulphate was used in 93%, mostly because it was
      expected to relieve breathlessness (70%) or reduce HDU/ITU admissions (51%). It
      was predominantly given to those patients with acute severe asthma (84%) and life
      threatening exacerbations (87%), with most stating they would give the drug if
      there was no response to repeated nebulisers (68%). In comparison, nebulised
      magnesium sulphate was only used in two emergency departments (1%). The main
      reason for not administering the drug via a nebuliser was insufficient evidence
      (51%). CONCLUSIONS: Intravenous magnesium sulphate is widely used for acute
      asthma, usually for patients with severe or life-threatening asthma who have not
      responded to initial treatment. Nebulised magnesium sulphate, by contrast, is
      hardly used at all. The use of intravenous magnesium sulphate is more extensive
      than current guidelines or available evidence would appear to support.

PMID- 19850801
TI  - Relationship between equipment and infrastructure for pandemic influenza and
      performance in an avian flu drill.
AB  - BACKGROUND: Effective preparedness for pandemic influenza necessitates
      acquisition and maintenance of vital equipment and infrastructure. The aim of
      this study was to investigate the relationship between the level of hospital
      preparedness relating to infrastructure and equipment and performance of the
      hospital in an avian flu drill. METHODS: The levels of preparedness of the
      infrastructure and equipment for pandemic influenza of all 24 general hospitals
      were evaluated using a tool developed for this purpose. The hospital evaluation
      scores were then compared with the scores obtained by the hospitals in a
      simulated avian flu drill. RESULTS: The overall scores of equipment and
      infrastructure for pandemic influenza of general hospitals ranged from 67% to
      100%. Comparison of the overall level of preparedness of equipment and
      infrastructure for pandemic influenza with the overall scores achieved in the
      avian flu drill revealed a medium correlation. A medium correlation was also
      found between stockpiling of medications and performance in the avian flu drill.
      No correlations were found between operating infrastructure, availability of
      protective measures and medical forms and performance in the avian flu drill.
      CONCLUSIONS: This study has identified benchmarks of infrastructure and equipment
      required for managing a pandemic influenza event and evaluating the level of
      emergency preparedness of the hospital. The significant relationship between
      maintaining stockpiles of antiviral medications for patients and staff and
      performance in an avian flu drill emphasises its importance in the process of
      maintaining emergency preparedness for a pandemic influenza outbreak.

PMID- 19850802
TI  - Images in emergency medicine. Winged scapula as the presenting symptom of
      Guillain-Barre syndrome.

PMID- 19850803
TI  - Derivation and validation of a sensitive IMA cutpoint to predict cardiac events
      in patients with chest pain.
AB  - OBJECTIVES: In patients with acute chest pain, we derived a cutpoint for
      ischaemia-modified albumin (IMA) and prospectively validated this cutpoint to
      predict 30-day major adverse cardiac events (MACEs). METHODS: We prospectively
      recruited a derivation cohort (18-month period) to establish a serum IMA cutpoint
      targeting 80% sensitivity. This was followed by a prospective validation cohort
      study of emergency department patients with acute chest pain at two university
      hospitals over a 3-month period. A MACE was defined as myocardial infarction,
      revascularisation or death at 30-day follow-up. RESULTS: In the derivation cohort
      of 151 patients, the IMA cutpoint that achieved 80% sensitivity for MACEs was 75
      KU/litre. The sensitivity was prospectively validated in 171 patients
      consecutively enrolled, of whom 106 underwent multiple-biomarker analysis (19.8%
      MACE rate, 81% sensitivity of IMA). Furthermore, IMA by itself (81%, p<0.01) and
      in combination with initial highly sensitive cardiac troponin T (hsTnT) (90%,
      p<0.001) had significantly higher sensitivity than initial hsTnT (29%) for
      prediction of MACEs. CONCLUSIONS: We prospectively validated the sensitive IMA
      cutpoint of 75 KU/litre with 80% sensitivity for MACEs in patients with acute
      chest pain. Our data suggest that IMA alone and in combination with initial hsTnT
      are more sensitive than the initial hsTnT for MACEs.

PMID- 19850804
TI  - Images in emergency medicine. Pulmonary artery pseudoaneurysm.

PMID- 19850805
TI  - The toddler refusing to weight-bear: a revised imaging guide from a case series.
AB  - BACKGROUND: The previously mobile child who refuses to walk or weight-bear is a
      common presentation to the accident and emergency department, for which there are
      a number of causes. One uncommon cause is discitis, an inflammatory process of
      the intervertebral disc, which is easily diagnosed with spinal magnetic resonance
      imaging (MRI). A case series of three patients is presented of non-weight-bearing
      children in whom there was a delay in making the diagnosis of lumbosacral
      discitis. None presented with back pain, spinal symptoms or abnormal neurological
      findings, and a full range of movement of both hips was found. METHODS: All
      patients underwent conventional radiography and ultrasound, but diagnoses were
      made on spinal MRI, with two patients undergoing bone scintigraphy before this.
      RESULTS: The mean delay was 15.6 days (range 13-20) from presentation at the
      hospital to MRI. All three patients made a good clinical recovery with
      intravenous antibiotics. CONCLUSION: These cases are presented in order to
      heighten the awareness of this disease entity and its imaging findings, and
      suggest new guidelines for the appropriate radiological investigations in this
      clinical setting.

PMID- 19850806
TI  - Predicting the complicated neutropenic fever in the emergency department.
AB  - OBJECTIVES: The purpose of this study was to identify independent factors that
      can be used to predict whether febrile neutropenic patients who appear healthy at
      presentation will develop subsequent complications, using variables that are
      readily available in the emergency department (ED). METHOD: The medical records
      of 192 episodes in which the patients presented to the ED with neutropenic fever
      resulting from chemotherapy, with an alert mental state and haemodynamic
      stability were retrospectively reviewed. Endpoints examined were fever response
      to administered antibiotics, death or severe medical complications during
      hospitalisation. RESULTS: Thirty-eight episodes of neutropenic fever with
      complicated outcomes were identified from among a total of 192 episodes. Three
      parameters emerged as independent factors for the prediction of neutropenic fever
      with complications in the multivariate regression analysis: platelet count (130
      450 x 10(3) cells/mm(3)) <50 000 cells/mm(3), serum C-reactive protein (CRP, 0.1
      1 mg/dl) >10 mg/dl and pulmonary infiltration on chest x ray. CONCLUSIONS:
      Platelet count, CRP and pulmonary infiltration on chest x ray at presentation
      could be used to identify febrile neutropenic patients who will develop
      complications, and these factors may be useful in making treatment-related
      decisions in the ED.

PMID- 19850807
TI  - Images in emergency medicine. Pain in the leg after jogging.

PMID- 19850808
TI  - Effects of bed height on the performance of chest compressions.
AB  - OBJECTIVES: The correct chest compression technique was emphasised to enhance the
      result of cardiopulmonary resuscitation in the 2005 guidelines. The present study
      compared the effects of different bed heights, including a bed at knee height, on
      the performance of chest compressions. METHODS: Twenty-four healthcare providers
      participated in this study. Knee height was defined as the baseline bed height.
      Bed heights were adjusted to 10 and 20 cm above the baseline and 10 and 20 cm
      below the baseline. At the five bed heights, chest compressions were performed
      for 2 minutes, and the compression rate was maintained at 100 per minute, with
      audible feedback. RESULTS: The mean compression depths (MCD) were 28.3 mm (SD
      10.7; knee height +20 cm), 32.3 mm (SD 9.2; knee height +10 cm), 32.7 mm (SD 8.5;
      knee height), 32.3 mm (SD 9.0; knee height -10 cm) and 31.1 mm (SD 8.5; knee
      height -20 cm). The MCD was significantly lower at knee height plus 20 cm
      (p<0.001). CONCLUSION: The performance of chest compressions decreased when the
      bed height was 20 cm higher than the knee height of the rescuer.

PMID- 19850809
TI  - Use of a control test to aid pH assessment of chemical eye injuries.
AB  - Chemical burns of the eye represent 7.0%-9.9% of all ocular trauma. Initial
      management of ocular chemical injuries is irrigation of the eye and conjunctival
      sac until neutralisation of the tear surface pH is achieved.We present a case of
      alkali injury in which the raised tear film pH seemed to be unresponsive to
      irrigation treatment. Suspicion was raised about the accuracy of the litmus paper
      used to test the tear film pH. The error was confirmed by use of a control litmus
      pH test of the examining doctor's eyes. Errors in litmus paper pH measurement can
      occur because of difficulty in matching the paper with scale colours and drying
      of the paper, which produces a darker colour. A small tear film sample can also
      create difficulty in colour matching, whereas too large a sample can wash away
      pigment from the litmus paper. Samples measured too quickly after irrigation can
      result in a falsely neutral pH measurement. Use of faulty or inappropriate
      materials can also result in errors. We advocate the use of control litmus pH
      test in all patients. This would highlight errors in pH measurements and aid in
      the detection of the end point of irrigation.

PMID- 19850810
TI  - Images in emergency medicine. The mark of the dragon.

PMID- 19850811
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bet 1: steroids for patients with vestibular neuronitis.

PMID- 19850813
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bet 2: eccentric exercise in the treatment of achilles tendinopathy.

PMID- 19850814
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bet 3: do buckle fractures of the paediatric wrist require follow up?

PMID- 19850815
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bet 4: the use of ultrasound in the diagnosis of paediatric wrist
      fractures.

PMID- 19850816
TI  - The Tough Guy prehospital experience: patterns of injury at a major UK endurance
      event.
AB  - BACKGROUND: Data from mass gathering events help when planning allocation of
      resources and in setting standards of care. There is currently a lack of data
      from the UK. AIM: To determine the frequency of injuries and hospital transfer
      rates at a large outdoor endurance event. METHODS: 251 patient attendances from
      four consecutive events over 2 years (two summers two winters; 2006-2007) were
      analysed. RESULTS: 1%-2% of contenders required medical help. Hypothermia (n =
      84), soft tissue problems (n = 71) and musculoskeletal problems (n = 51) were the
      most common conditions encountered. 4% of patients required immediate transfer to
      the hospital. The medical team was able to prevent 31 hospital transfers, which
      represents a reduction of 78%. 13% of cases specifically required a doctor who
      was able to prevent more immediate hospital transfers than other care givers. The
      majority of injuries were classified as minor (n = 228), with the remaining as
      intermediate (n = 23); there were no life-threatening injuries or deaths. No
      patient required intravenous fluid. Overall, in winter, more patients were
      treated when compared with summer (157 vs 94). There were significantly more
      retirements in winter (69 vs 22, p<0.001), although hospital transfer rates were
      similar. CONCLUSIONS: Medical teams should plan for casualty rates of 1%-2% of
      competitors and hospital transfer rates of approximately 5% of patients treated.
      Outdoor events in winter create more casualties than in summer and require
      greater resources. Trauma and exposure injuries are common; critical illness is
      uncommon. An adequately equipped and skilled medical team reduces hospital
      admissions.

PMID- 19850818
TI  - An evaluation of an educational intervention to reduce inappropriate cannulation
      and improve cannulation technique by paramedics.
AB  - BACKGROUND: Intravenous cannulation enables administration of fluids or drugs by
      paramedics in prehospital settings. Inappropriate use and poor technique carry
      risks for patients, including pain and infection. We aimed to investigate the
      effect of an educational intervention designed to reduce the rate of
      inappropriate cannulation and to improve cannulation technique. METHOD: We used a
      non-randomised control group design, comparing two counties in the East Midlands
      (UK) as intervention and control areas. The educational intervention was based on
      Joint Royal Colleges Ambulance Liaison Committee guidance and delivered to
      paramedic team leaders who cascaded it to their teams. We analysed rates of
      inappropriate cannulation before and after the intervention using routine
      clinical data. We also assessed overall cannulation rates before and after the
      intervention. A sample of paramedics was assessed post-intervention on
      cannulation technique with a "model" arm using a predesigned checklist. RESULTS:
      There was a non-significant reduction in inappropriate (no intravenous fluids or
      drugs given) cannulation rates in the intervention area (1.0% to 0%) compared
      with the control area (2.5% to 2.6%). There was a significant (p<0.001) reduction
      in cannulation rates in the intervention area (9.1% to 6.5%; OR 0.7, 95% CI 0.48
      to 1.03) compared with an increase in the control area (13.8% to 19.1%; OR 1.47,
      95% CI 1.15 to 1.90), a significant difference (p<0.001). Paramedics in the
      intervention area were significantly more likely to use correct hand-washing
      techniques post-intervention (74.5% vs. 14.9%; p<0.001). CONCLUSION: The
      educational intervention was effective in bringing about changes leading to
      enhanced quality and safety in some aspects of prehospital cannulation.

PMID- 19850819
TI  - Spontaneous intraparenchymal tension pneumocephalus triggered by compulsive
      forceful nose blowing.
AB  - The case is described of a 50-year-old man, treated for 10 years in an outpatient
      psychiatric clinic for an obsessive compulsive disorder, who presented with acute
      loss of consciousness after forceful nose blowing. A CT scan revealed an
      intraparenchymal air collection with tension signs in the left frontal lobe and a
      bone defect in the roof of the ethmoid sinus. After emergency left frontal
      craniotomy and dura opening, the gaseous collection was evacuated by a
      ventricular catheter inserted into the brain and the bone defect was repaired
      with pericranium flap and muscle. The postoperative course was uneventful with
      neurocognitive improvement and regained motility. Spontaneous tension
      pneumocephalus is a rare life-threatening condition which is often caused by a
      bone defect near the tegmen tympani. This case illustrates both an unusual cause
      and a unique surgical treatment for spontaneous tension intraparenchymal
      pneumocephalus. It can be a dangerous entity with potential for early mortality
      and long-term morbidity if not promptly decompressed. The pathogenesis, diagnosis
      and surgical strategies for spontaneous tension pneumocephalus are briefly
      discussed.

PMID- 19850820
TI  - Bullet embolisation from the right subclavian vein to the right ventricle: a case
      report.
AB  - Bullet embolism to the heart is an unusual complication of penetrating gunshot
      injuries. A bullet may reach the heart by direct cardiac penetration or entry
      into the peripheral venous system with embolisation to the heart, which must be
      differentiated. This is a report of an unusual case of bullet embolism to the
      heart that was extracted by direct cardiotomy without cardiopulmonary bypass.

PMID- 19850821
TI  - Subclavian vein thrombosis following clavicular fracture.
AB  - A very rare case is presented of a woman with subclavian vein thrombosis that
      resulted from a fragment of her fractured clavicle impinging on the subclavian
      vein.

PMID- 19850823
TI  - Is propofol a safe and effective sedative for relocating hip prostheses?

PMID- 19850825
TI  - Photoreceptor inner/outer segment defect imaging by spectral domain OCT and
      visual prognosis after macular hole surgery.
AB  - PURPOSE: To evaluate photoreceptor inner/outer segment (IS/OS) defect parameters
      by using spectral domain-optical coherence tomography (SD-OCT) for correlation
      with visual outcomes in macular hole surgery (MHS). METHODS: This study was an
      interventional, retrospective case series. Twenty-three eyes (23 patients) were
      examined by SD-OCT before and after (median, 2.3 months) anatomically successful
      MHS. Two formats of OCT were analyzed: linear (raster) and composite (partial
      fundus image). Factors that may have confounded IS/OS measurements were
      controlled by using weighting and normalization of data. The main outcome
      measures were diameter and area of the IS/OS defect, weighted area of the IS/OS
      defect, macular density ratio (MDR), healing pattern of the macular hole, and
      preoperative and postoperative best corrected visual acuity (BCVA). RESULTS:
      Poorer preoperative BCVA correlated with larger preoperative diameter of the
      IS/OS defect (P = 0.005). A greater improvement in BCVA correlated with a larger
      preoperative area of IS/OS defect (P = 0.038) and smaller MDR (P = 0.012). Poorer
      postoperative BCVA correlated with a larger postoperative diameter of the IS/OS
      defect (P = 0.010), larger weighted postoperative area of IS/OS defect calculated
      by raster scan (P = 0.013), larger postoperative area of IS/OS defect measured
      from the partial fundus image (P = 0.003), and apparent glial sealing pattern on
      SD-OCT (P = 0.0005). The shape of the IS/OS defect area was round and regular
      before surgery, but irregular afterward. CONCLUSIONS: BCVA after MHS correlates
      with objectively ascertainable SD-OCT measurements of IS/OS defects and other
      features. The postoperative area of the IS/OS defect, when directly measured,
      correlates more strongly with BCVA than do linear-based measurements, perhaps
      because of the irregular shape of the IS/OS defect after surgery.

PMID- 19850826
TI  - Experience-dependent regulation of NMDA receptor subunit composition and
      phosphorylation in the retina and visual cortex.
AB  - Purpose. Experimental manipulation of experience during development can have
      profound effects on the functioning of the resulting circuits. N-methyl-d
      aspartate glutamate receptor (NMDAR) activity is required for the establishment
      and refinement of neural circuits during development. In the present study, the
      authors addressed the issue of experience-dependent regulation of NMDARs by
      examining the effects of visual experience and deprivation on subunit composition
      and subunit phosphorylation of NMDAR in the retina and visual cortex. Methods.
      Total homogenates were prepared from retinas and visual cortices of 30-day-old
      (P30) Wistar rats, raised either in a normal 12-hour light/12-hour dark cycle
      (normal-reared [NR]) or in complete darkness from birth (dark-reared [DR]). Some
      of the DR animals were exposed to light for 6 hours at P30 (DR+6h).
      Immunoblotting was performed for the NMDAR subunits, NR2A and NR2B, and for the
      phosphorylated NR2B subunit protein at serine 1303 (pNR2B-Ser1303). Results. Dark
      rearing for 1 month decreased the NR2A/NR2B ratio and increased the level of
      phosphorylation of NR2B subunit at Ser1303 in the retina and visual cortex. Light
      exposure at P30 reversed the effects of visual deprivation on NMDAR composition
      and NR2B phosphorylation in both regions. Conclusions. These results indicated
      that NMDAR subunit composition and NR2B phosphorylation at Ser1303 is regulated
      bidirectionally by visual experience and deprivation in rat retina and visual
      cortex.

PMID- 19850827
TI  - Expression and biophysical characterization of voltage-gated sodium channels in
      axons and growth cones of the regenerating optic nerve.
AB  - PURPOSE: Successful regeneration and re-establishment of synaptic connections in
      the adult central nervous system is a complex process determined by both the
      exterior environment and the endogenous neural activity of the regenerating
      growth cones. The purpose of this study was to determine the expression and
      properties of voltage-gated sodium channels (Na(v)) expressed by regenerating
      growth cones. METHODS: Na(v) channels were studied in an organotypic explant
      culture of the adult rat retina by immunocytochemistry and whole-cell, patch
      clamp recordings. RESULTS: Regenerating axons and growth cones, but not glial
      processes, expressed Na(v) channels. Whole-cell, current-clamp recordings from
      growth cones displayed a high input resistance of 1.29 GOmega and a resting
      membrane potential of -69.0 mV. All growth cones responded to depolarizing
      voltage steps with fast, transient, inward currents mediated by Na(+) ions,
      followed by slow, sustained outward K(+) currents. Half-maximum activation
      clustered in two groups, suggesting the presence of at least two Na(v) channel
      isoforms. Steady state inactivation and recovery from fast inactivation were
      characterized by a half-maximum value of -69.7 mV and by a time constant of 3.64
      ms, respectively. Injection of depolarizing current steps larger than threshold (
      29.3 mV) consistently induced a single action potential, whereas ganglion cell
      bodies responded to above-threshold stimulation with a series of fast, all-or
      none action potentials. CONCLUSIONS: These experiments describe for the first
      time the biophysical properties of Na(v) channels recorded from the growth cones
      of regenerating retinal ganglion cells and contrast their properties with those
      of adult retinal ganglion cells.

PMID- 19850829
TI  - Inhibition of retinal detachment-induced apoptosis in photoreceptors by a small
      peptide inhibitor of the fas receptor.
AB  - Purpose. To test the effect of a small peptide inhibitor (Met12) of the Fas
      receptor on the activation of extrinsic and intrinsic apoptosis pathways after
      retinal detachment. Methods. Retinal-RPE separation was created in Brown Norway
      rats by subretinal injection of 1% hyaluronic acid. Met12, derived from the Fas
      binding extracellular domain of the oncoprotein Met, was injected into the
      subretinal space at the time of separation. A mutant peptide and vehicle
      administered in a similar fashion acted as inactive controls. The extrinsic
      apoptotic pathway was induced in 661W cells using a Fas-activating antibody in
      the presence or absence of Met12. Caspase 3, caspase 8, and caspase 9 activities
      were measured with calorimetric and luminescent assays in retinal extracts and
      cell lysates. Terminal deoxynucleotidyl transferase dUTP nick-end labeling
      (TUNEL) was performed in retinal sections 3 days after separation. Histology was
      performed in retinal sections 2 months after retinal detachment. Results. Met12
      inhibited Fas-induced caspase 8 activation in 661W cells. Similarly,
      administration of Met12 into the subretinal space inhibited the activation of
      caspase 3, caspase 8, and caspase 9 after retinal detachment. This corresponded
      to a decreased level of TUNEL-positive staining of photoreceptors after retinal
      RPE separation in animals that received Met12, but not inactive mutant, peptide
      treatment. After 2 months, the outer nuclear layer was significantly thicker, and
      the photoreceptor count was higher in animals treated with subretinal Met12.
      Conclusions. The small peptide Met12 may serve as a photoreceptor-protective
      agent in the setting of retinal-RPE separation.

PMID- 19850828
TI  - Divergent roles of nitric oxide and rho kinase in vasomotor regulation of human
      retinal arterioles.
AB  - PURPOSE: Although the arteriolar segment contributes to flow regulation, there is
      sparse information at the single microvessel level on how vasomotor function is
      regulated in the human retina. The authors have previously reported
      vasoreactivity and its underlying mechanisms in isolated porcine retinal
      arterioles. Herein, they studied human retinal arterioles for comparison.
      METHODS: Retinal tissues were obtained from seven patients undergoing
      enucleation. Human and porcine retinal arterioles were isolated and pressurized
      to 55 cm H(2)O luminal pressure for vasoreactivity study using videomicroscopic
      techniques. RESULTS: Isolated human and porcine retinal arterioles developed
      myogenic tone and dilated dose dependently to bradykinin, adenosine, and sodium
      nitroprusside. Stepwise increases in luminal flow produced graded dilation with
      approximately 60% dilation at the highest flow tested. Nitric oxide (NO) synthase
      inhibitor L-NAME nearly abolished dilations to bradykinin and flow and attenuated
      the adenosine-induced dilation without altering the response to nitroprusside.
      Endothelin-1 caused dose-dependent constriction. Rho kinase (ROCK) inhibitor H
      1152 blocked both myogenic tone and endothelin-1-induced constriction. Responses
      of retinal arterioles to all agonists and increased flow were similar between
      pigs and humans. CONCLUSIONS: Isolated human retinal arterioles dilate to
      bradykinin and increased flow in an NO-dependent manner. NO contributes, in part,
      to adenosine-induced vasodilation. Conversely, ROCK activation mediates myogenic
      tone and endothelin-1-induced vasoconstriction. Similarities in these vasoactive
      responses and the underlying mechanisms between human and porcine retinal
      arterioles support the latter as a viable experimental model of the human retinal
      microcirculation.

PMID- 19850830
TI  - Retinal basement membrane abnormalities and the retinopathy of Alport syndrome.
AB  - PURPOSE: To determine the effects of X-linked and autosomal recessive Alport
      syndrome on retinal basement membranes and how these result in the characteristic
      perimacular dot-and-fleck retinopathy, lozenge, and macular hole. METHODS: The
      type IV collagen chains present in the normal retina were determined
      immunohistochemically. Ten patients with Alport syndrome underwent retinal
      photography and optical coherence tomography to determine the thickness of the
      internal limiting membrane (ILM) by segmentation analysis, the layers affected by
      the retinopathy, and any correlates of the lozenge and macular hole. Bruch's
      membrane was examined directly by electron microscopy in a donated Alport eye.
      RESULTS: The alpha3alpha4alpha5 type IV collagen network was present in the
      normal ILM and in the retinal pigment epithelium basement membrane of Bruch's
      membrane. In Alport syndrome, the ILM/nerve fiber layer and Bruch's membrane were
      both thinned. The dot-and-fleck retinopathy corresponded to hyperreflectivity of
      the ILM/nerve fiber layer in the distribution of the nerve fiber layer. The
      lozenge and macular hole corresponded to temporal macular thinning. The thinning
      across the whole retina was principally due to thinning of the ILM/nerve fiber
      layer and inner nuclear layer. CONCLUSIONS: The Alport dot-and-fleck retinopathy
      results primarily from abnormalities in the ILM/nerve fiber layer rather than in
      Bruch's membrane. Thinning of the ILM/nerve fiber layer contributes to the
      retinopathy, lozenge, and macular hole, possibly through interfering with
      nutrition of the overlying retina or clearance of metabolic by-products.

PMID- 19850831
TI  - Effect of acute increase in blood pressure on intraocular pressure in pigs and
      humans.
AB  - PURPOSE: To study the effect on intraocular pressure (IOP) of a sudden increase
      in blood pressure (BP) and of changes in partial pressure of CO(2) (pCO(2)).
      METHODS: Two experimental studies were conducted: in pigs (n = 7), where BP was
      reduced by intravenous injection of sodium nitroprusside and increased by
      injection of angiotensin II; and in humans (n = 17 healthy subjects), where BP
      was increased by two types of isometric exercise (squatting and handgripping)
      performed for 2 minutes; IOP and pCO(2) were measured every 30 seconds during
      separate tests (rest, hyperventilation, isometric exercise) and then after 1, 3,
      6, and 10 minutes of rest. RESULTS: In pigs, there is a linear relationship
      between BP and IOP variations: DeltaIOP = 1.21 DeltaBP - 0.14 (P < 0.001). In
      humans, this linear relationship is as follows: DeltaIOP = 0.40 DeltaBP + 0.85 (P
      < 0.001) for squatting and DeltaIOP = 0.54 DeltaBP + 0.55 (P = 0.02) for
      handgripping. BP and IOP increases are greater with squatting than with
      handgripping (53% vs. 46%, P = 0.05 and 46% vs. 35%, P = 0.03, respectively).
      Handgripping causes a greater fall in capnia than squatting does (P = 0.02).
      Capnia and IOP are positively correlated (P < 0.001). CONCLUSIONS: The
      pharmacological approach in animals and the study of isometric exercise in humans
      show that IOP rises significantly and rapidly with kinetics close to those of BP,
      and the two values are linearly related. The absence of variation in capnia and
      the greater increase in BP during squatting may explain the greater increase in
      IOP during this exercise compared to handgripping.

PMID- 19850832
TI  - Rapid detection of fungal keratitis with DNA-stabilizing FTA filter paper.
AB  - Purpose. Polymerase chain reaction (PCR) is increasingly important for the rapid
      detection of fungal keratitis. However, techniques of specimen collection and DNA
      extraction before PCR may interfere with test sensitivity. The purpose of this
      study was to investigate the use of DNA-stabilizing FTA filter paper (Indicating
      FTA filter paper; Whatman International, Ltd., Maidstone, UK) for specimen
      collection without DNA extraction in a single-step, nonnested PCR for fungal
      keratitis. Methods. Specimens were collected from ocular surfaces with FTA filter
      discs, which automatically lyse collected cells and stabilize nucleic acids.
      Filter discs were directly used in single-step PCR reactions to detect fungal
      DNA. Test sensitivity was evaluated with serial dilutions of Candida albicans,
      Fusarium oxysporum, and Aspergillus fumigatus cultures. Test specificity was
      analyzed by comparing 196 and 155 healthy individuals from Switzerland and Egypt,
      respectively, with 15 patients with a diagnosis of microbial keratitis. Results.
      PCR with filter discs detected 3 C. albicans, 25 F. oxysporum, and 125 A.
      fumigatus organisms. In healthy volunteers, fungal PCR was positive in 1.0% and
      8.4% of eyes from Switzerland and Egypt, respectively. Fungal PCR remained
      negative in 10 cases of culture-proven bacterial keratitis, became positive in 4
      cases of fungal keratitis, but missed 1 case of culture-proven A. fumigatus
      keratitis. Conclusions. FTA filter paper for specimen collection together with
      direct PCR is a promising method of detecting fungal keratitis. The analytical
      sensitivity is high without the need for a semi-nested or nested second PCR, the
      clinical specificity is 91.7% to 99.0%, and the method is rapid and inexpensive.

PMID- 19850833
TI  - Identification of barriers to retinal engraftment of transplanted stem cells.
AB  - PURPOSE: Intraocular stem cell transplantation may be therapeutic for retinal
      neurodegenerative diseases such as glaucoma via neuronal replacement and/or
      neuroprotection. However, efficacy is hindered by extremely poor retinal graft
      integration. The purpose was to identify the major barrier to retinal integration
      of intravitreally transplanted stem cells, which was hypothesized to include the
      cellular and/or extracellular matrix (ECM) components of the inner limiting
      membrane (ILM). METHODS: Mesenchymal stem cells (MSCs) were cocultured on the
      vitreal surface of retinal explants. Retinal MSC migration was compared between
      control explants and explants in which portions of the ILM were removed by
      mechanical peeling; the inner basal lamina was digested with collagenase; and
      glial cell reactivity was selectively modulated with alpha-aminoadipic acid
      (AAA). In vivo, the MSCs were transplanted after intravitreal AAA or saline
      injection into glaucomatous rat eyes. RESULTS: Retinal MSC migration correlated
      positively with the amount of peeled ILM, whereas enzymatic digestion of the
      basal lamina was robust but did not enhance MSC entry. In contrast, AAA treatment
      suppressed glial cell reactivity and facilitated a >50-fold increase in MSC
      migration into retinal explants. In vivo analysis showed that AAA treatment led
      to a more than fourfold increase in retinal engraftment. CONCLUSIONS: The results
      demonstrated that the ECM of the inner basal lamina is neither necessary nor
      sufficient to prevent migration of transplanted cells into the neural retina. In
      contrast, glial reactivity was associated with poor graft migration. Targeted
      disruption of glial reactivity dramatically improved the structural integration
      of intravitreally transplanted cells.

PMID- 19850834
TI  - A novel haplotype with the R345W mutation in the EFEMP1 gene associated with
      autosomal dominant drusen in a Japanese family.
AB  - PURPOSE: To describe ophthalmic and molecular genetic findings in a family of
      Japanese patients with Malattia leventinese (ML)/Doyne honeycomb retinal
      dystrophy (DHRD), also known as autosomal dominant drusen. METHODS: Four patients
      with ML/DHRD, including a 42-year-old female proband, were ascertained. The
      proband underwent complete ophthalmic examinations, including fundus and
      electrodiagnostic investigations, and Humphrey visual field (VF) perimetry.
      Mutation screening of the EFEMP1 gene and haplotype analysis were performed in
      the family, an Indian ML/DHRD family, and a branch of 1 of 39 ML/DHRD families in
      the United States, in which all affected patients shared a common haplotype.
      RESULTS: A heterozygous missense mutation (p.R345W) was identified in all four
      Japanese patients and in affected patients of the other two families. This
      mutation was the only mutation that has been exclusively found in the gene. The
      disease haplotype in the Japanese family was different from those of the other
      two families. Clinically, central retinas were prominently affected in the
      proband and her mother, and subsequently the proband developed subfoveal
      choroidal neovascularization in the left eye, whereas her younger sister with the
      mutation, who was asymptomatic, exhibited only fine macular drusen. Long-term
      follow-up of Humphrey VF and multifocal-electroretinography (mfERG) in the
      proband also revealed progressive attenuation of macular function in the right
      eye. CONCLUSIONS: This is the first report to describe a Japanese family with
      variable expressivity of ML/DHRD, in which a novel disease haplotype was
      identified. Humphrey VF and mfERG testing may be helpful in determining the long
      term outcome of macular function.

PMID- 19850835
TI  - Noncoding variant in the complement factor H gene and risk of exudative age
      related macular degeneration in a Chinese population.
AB  - PURPOSE: To investigate whether the previously reported noncoding variant of the
      complement factor H (CFH) gene and two coding variants of the complement
      component 3 (C3) gene are associated with exudative age-related macular
      degeneration (AMD) in Chinese patients. METHODS: One hundred fifty Chinese
      patients with exudative AMD and 161 control individuals without AMD were
      recruited for the study. Genomic DNA was extracted from blood leukocytes. The
      noncoding variant of the CFH gene (rs1410996) and two coding variants of the C3
      gene (rs2230199 and rs1047286) were genotyped by polymerase chain reaction (PCR)
      followed by allele-specific restriction enzyme digestion and direct sequencing.
      RESULTS: Significant association was detected for exudative AMD with the CFH
      noncoding variant rs1410996. Frequencies of the risk C allele at rs1410996 were
      72.0% in AMD cases versus 55.6% in controls (P < 0.001). The odds ratio for risk
      of AMD was 1.71 (95% confidence interval [CI], 0.82-3.54) for heterozygous TC
      genotype and 3.85 (95% CI, 1.84-8.05) for homozygous CC genotype compared with
      the wild TT genotype. In contrast, the C3 variants rs2230199 and rs1047286 were
      not associated with exudative AMD in the studied subjects. Frequencies of the
      risk G allele at rs2230199 and of the risk T allele at rs1047286 were 0.3% to
      1.0% in both cases and controls. CONCLUSIONS: The data suggest that the noncoding
      variant rs1410996 of the CFH gene moderately increased the risk of exudative AMD
      in a Chinese population. The C3 variants were rare and not associated with
      exudative AMD in this Chinese cohort.

PMID- 19850837
TI  - Live conjunctiva-associated lymphoid tissue analysis in rabbit under inflammatory
      stimuli using in vivo confocal microscopy.
AB  - PURPOSE: Conjunctiva-associated lymphoid tissue (CALT) plays an important role in
      ocular surface immunity. No study until now has been able to show its in vivo
      aspects, and few have demonstrated its reactions after pathologic patterns. The
      authors investigated in rabbit eyes the cell reactions occurring in the organized
      CALT during conjunctival inflammation models. METHODS: Using in vivo confocal
      microscopy (IVCM), the authors analyzed, for the first time in vivo inflammatory
      cell infiltration and circulation inside the lymph vessels in rabbit CALT after
      inflammatory stimuli (LPS, TNFalpha, LPS+/-anti-TNF). Cresyl violet staining was
      performed to observe the morphology of CALT, and immunohistology was performed in
      whole mount conjunctiva and cryosections for detecting CD45(+) lymphocytes. Human
      CALT in vivo aspects were also explored in a patient with vernal
      keratoconjunctivitis (VKC). RESULTS: The conjunctivitis model induced by LPS was
      characterized by inflammatory cell infiltration in the dome and intrafollicular
      layers of CALT and cell circulation inside the lymph vessels. TNF alone induced
      moderate inflammatory infiltration in CALT. However anti-TNF antibodies could
      significantly decrease LPS/TNFalpha-induced inflammation. CD45(+) lymphocytes
      were strongly expressed in the CALT after injection of LPS or TNFalpha at 4 hours
      and decreased with injection of anti-TNFalpha. The authors also showed the
      presence of the CALT pattern in VKC. CONCLUSIONS: The authors showed for the
      first time the in vivo aspects of normal and pathologic cell reactions in rabbit
      CALT after inflammatory stimuli. IVCM-CALT could be a pertinent tool in the
      future for the comprehension of ocular surface defense mechanisms, and
      inflammatory cell analysis in CALT could constitute a new criterion for
      evaluating ocular surface inflammation.

PMID- 19850836
TI  - The microbead occlusion model: a paradigm for induced ocular hypertension in rats
      and mice.
AB  - PURPOSE: Elevated intraocular pressure (IOP) is an important risk factor for
      glaucoma. Animal models often involve techniques for IOP elevation that are
      surgically invasive. Here the authors describe a novel and relatively simple
      method for inducing a highly consistent, modest, and repeatable elevation in IOP
      for rats and mice. METHODS: IOP was elevated unilaterally by injection of
      polystyrene microbeads into the anterior chamber to occlude aqueous outflow in
      rats (2.5-7 microL) and mice (1 microL). The fellow eye received an equivalent
      saline injection as internal control. The authors used tonometry to measure
      microbead-induced IOP elevations. Optic nerves were processed histologically to
      determine axon loss. RESULTS: For rats, a single injection of microbeads raised
      IOP by 21% to 34%, depending on volume, for approximately 2 weeks, though they
      were not tracked to full recovery. IOP in the saline-injected eye was constant.
      An additional injection (5 microL) extended the elevation to 8 weeks. Cumulative
      pressure exposure for both injections increased linearly. For mice, a single 1
      microL injection of microbeads elicited a highly regular 30% elevation in IOP
      that persisted for more than 3 weeks, with a linear rise in cumulative pressure
      exposure. For both rats and mice, interanimal variability on a given day was
      modest, approximately 5% of the mean IOP measurement. Extended elevations (4-5
      weeks) induced approximately a 20% loss of axons in both rats and mice.
      CONCLUSIONS: These data support a novel and flexible model of modest ocular
      hypertension with axon loss. The maximal duration of IOP elevation will be
      further characterized in future studies.

PMID- 19850838
TI  - Cross-sectional anatomic configurations of peripapillary atrophy evaluated with
      spectral domain-optical coherence tomography.
AB  - PURPOSE: To evaluate the cross-sectional configurations of peripapillary atrophy
      (PPA)-alpha and -beta in ophthalmologically normal subjects using spectral domain
      optical coherence tomography (SD-OCT). METHODS: One hundred twenty normal
      subjects had a complete ophthalmic examination including axial length
      measurement, standard automated perimetry, fundus imaging with photography, and
      SD-OCT (3D OCT-1000; Topcon Inc., Tokyo, Japan). PPA-alpha and -beta were
      identified in color photographs of the optic disc. Cross-sectional B-mode images
      of the peripapillary retina and sclera, including PPA-alpha and -beta obtained
      with SD-OCT, were analyzed. RESULTS: Of 120 normal eyes, 120 (100%) had PPA-alpha
      and 90 (75%) had PPA-beta. In OCT images of the peripapillary retina, the
      ganglion cell layer and the inner and outer plexiform layers were observed to end
      in a tapering fashion at the edge of the optic disc, whereas the retinal nerve
      fiber layer continued into the optic cup. The external limiting membrane (ELM),
      inner-outer segments (IS-OS), and retinal pigment epithelium(RPE)/Bruch's
      membrane complex were significantly more commonly absent before the optic disc
      edge within the PPA-beta compared with areas outside the PPA-beta (P < 0.0001).
      Specific findings in the peripapillary area including slope and step
      configurations of the scleral bed and hump- and wedge-shaped appearances of the
      RPE-Bruch's membrane complex were identified in 63 (52.5%), 6 (5.0%), 19 (15.8%),
      and 6 (5.0%) of 120 eyes, respectively. The presence of the step configuration
      was associated with myopia and longer axial length (P = 0.0014 and 0.0105,
      respectively). CONCLUSIONS: The cross-sectional anatomic configurations of the
      peripapillary atrophy were evaluated by using SD-OCT. The termination of the
      retinal layers and configurations of the scleral bed in the peripapillary area
      varied among normal subjects.

PMID- 19850839
TI  - Effects of human recombinant PEDF protein and PEDF-derived peptide 34-mer on
      choroidal neovascularization.
AB  - PURPOSE: Pigment epithelium-derived factor (PEDF) is a serpin with antiangiogenic
      properties. Previously, the authors showed that PEDF injected into the
      subconjunctiva reaches the choroid. Here, they examined the effects of PEDF
      polypeptide fragments on vessel sprouting and on choroidal neovascularization
      (CNV) after subconjunctival administration. METHODS: Recombinant human PEDF
      (rhuPEDF) was cleaved at its serpin-exposed loop by limited chymotrypsin
      proteolysis. Synthetic PEDF peptides 34-mer (Asp(44)-Asn(77)) and 44-mer (Val(78)
      Thr(121)) were used. Ex vivo chick aortic vessel sprouting assays were performed.
      CNV was induced in rats by laser injury of Bruch's membrane. Daily
      subconjunctival injections (0.01-10 pmol/d protein) were performed for 5 days
      starting at day of injury or at the seventh day after injury. New vessel volumes
      were quantified using optical sections of choroid/RPE flat-mounts labeled with
      isolectin-Ib4. PEDF distribution was evaluated by immunofluorescence of
      choroid/RPE/retina cross-sections. RESULTS: Full-length rhuPEDF, cleaved rhuPEDF,
      or peptide 34-mer exhibited ex vivo antiangiogenic activity, but peptide 44-mer
      was inefficient. PEDF immunostaining around CNV lesions diminished after laser
      injury. Subconjunctival administration of rhuPEDF or 34-mer at 0.1 pmol/d
      decreased CNV lesion volumes by 52% and 47%, respectively, whereas those of 44
      mer were similar to vehicle injections. Doses of 0.1 and 1 pmol/d rhuPEDF
      decreased fully developed CNV complex volumes by 45% and 50%, respectively,
      compared with vehicle injections. CONCLUSIONS: A functional region for the
      inhibition of vessel sprouting and CNV resides within the 34-mer region of PEDF.
      Furthermore, subconjunctival administration of optimal range dosages of rhuPEDF
      or 34-mer can suppress and regress rat CNV lesions, demonstrating that these
      agents reach the choroid/RPE complex as functionally active molecules.

PMID- 19850841
TI  - Microstructural alterations of retinal arterial blood column along the vessel
      axis in systemic hypertension.
AB  - Purpose. Image analysis by the retinal vessel analyzer (RVA) observes retinal
      vessels in their dynamic state online noninvasively along a chosen vessel
      segment. It has been found that high-frequency diameter changes in the retinal
      artery blood column along the vessel increase significantly in anamnestically
      healthy volunteers with increasing age and in patients with glaucoma during
      vascular dilation. This study was undertaken to investigate whether longitudinal
      sections of the retinal artery blood column are altered in systemic hypertension.
      Methods. Retinal arteries of 15 untreated patients with essential arterial
      hypertension (age, 50.9 +/- 11.9 years) and of 15 age-matched anamnestically
      healthy volunteers were examined by RVA. After baseline assessment, a
      monochromatic luminance flicker (530-600 nm; 12.5 Hz; 20 s) was applied to evoke
      retinal vasodilation. Differences in amplitude and frequency of spatial artery
      blood column diameter change along segments (longitudinal arterial profiles) of 1
      mm in length were measured and analyzed using Fourier transformation. Results. In
      the control group, average reduced power spectra (ARPS) of longitudinal arterial
      profiles did not differ when arteries changed from constriction to dilation. In
      the systemic hypertension group, ARPS during constriction, baseline, and
      restoration were identical and differed from ARPS during dilation (P < 0.05).
      Longitudinal arterial profiles in both groups showed significant dissimilitude at
      baseline and restoration (P < 0.05). Conclusions. The retinal artery blood column
      demonstrates microstructural alterations in systemic hypertension and is less
      irregular along the vessel axis during vessel dilation. These microstructural
      changes may be an indication of alterations in vessel wall rigidity, vascular
      endothelial function, and smooth muscle cells in this disease, leading to
      impaired perfusion and regulation.

PMID- 19850840
TI  - A fungal pH-responsive signaling pathway regulating Aspergillus adaptation and
      invasion into the cornea.
AB  - PURPOSE: To investigate the role of PalB and PacC, two components of a pH
      responsive signal-transduction pathway of Aspergillus nidulans, during the
      pathogenesis of fungal infection of the cornea. METHODS: Fungal strains included
      an A. nidulans wild-type isolate (A83), loss-of-function A. nidulans mutants of
      the palB (B7) or pacC (C6309) genes, and reconstituted genotypic strains (B7R and
      C6309R). Doubling times and radial growth rates were examined under neutral and
      acidic conditions. Corneal virulence was assessed ex vivo by topical inoculation
      of scarified porcine or human corneas with A. nidulans strains maintained in
      buffered medium until histologic examination after days 1, 3, and 5. RESULTS: In
      vitro growth kinetics were similar for A. nidulans strains in liquid medium at pH
      6.0 (P = 0.24) and 7.3 (P = 0.75). The pacC mutant C6309 grew more slowly (P <
      0.001) on solid medium, whereas palB and pacC rescuants had growth kinetics
      comparable to those of the wild-type. Wild-type A. nidulans germinated on porcine
      corneas and produced hyphae that progressively invaded the stroma, reaching an
      average maximum penetration of 56% +/- 9% at 5 days after exposure. In contrast,
      hyphal invasion was significantly less by mutant strains B7 (P = 0.005) and C6309
      (P = 0.003). Fungal penetration by C6309 was also significantly less than the
      wild-type (P = 0.0005) on explanted human corneas. Both fungal rescuants showed
      stromal invasion similar to the wild-type. CONCLUSIONS: Corneal invasion by
      filamentous hyphae is attenuated by palB and pacC mutant strains of A. nidulans.
      The PacC pathway is involved in regulating fungal filamentation during ex vivo
      Aspergillus infection of the cornea.

PMID- 19850842
TI  - Killer cell immunoglobulin-like receptors in HLA-B27-associated acute anterior
      uveitis, with and without axial spondyloarthropathy.
AB  - PURPOSE: To determine associations between polymorphic genes that encode KIRs and
      their HLA class I ligands in patients with HLA-B27-associated acute anterior
      uveitis (AAU), with and without axial spondyloarthropathy (axial SpA). METHODS:
      Molecular DNA typing methods were used to define the frequencies of variable KIR
      genes and their relevant HLA class I ligands in HLA-B27(+) (B27(+)) Caucasian
      subjects with AAU and 429 healthy Caucasian control subjects. The patients were
      evaluated for axial SpA based on their histories using published criteria.
      RESULTS: Of 143 Caucasian subjects with AAU, 71 (49.6%) had features of axial
      SpA. The only difference between cases and controls in KIR gene frequencies was a
      trend toward fewer activating KIRs in subjects with AAU with axial SpA, which
      reached statistical significance for 2DS5 (P = 0.025, corrected P [P(c)] = 0.05;
      odds ratio [OR], 0.48; 95% CI, 0.25-0.90). The 3DL1+Bw4(T80) combination
      implicated in weak inhibition was more frequent in subjects with AAU than in
      control subjects (P = 2.73 x 10(-28), P(c) = 8.2 x 10(-27); OR, 13.5; 95% CI,
      7.73-23.68). The 2DL1+HLA-C2 combination was decreased in subjects with axial SpA
      compared with subjects with AAU without axial SpA (P = 0.022; P(c) = NS; OR,
      0.43; 95% CI, 0.21-0.88). CONCLUSIONS: Evidence was found of a role for KIR-HLA
      combinations that trigger weaker inhibition in subjects with AAU. Furthermore,
      there was a trend toward fewer KIR3DS1, -2DS1, and -2DS5 in AAU patients with
      axial SpA, which have been implicated in NK cell activation. HLA-B27(+) without
      KIR2DS3 (and -2DS1 and -3DS1) may fail to trigger an early NK cell response to
      clear antigenic stimuli, which may in part contribute to disease pathogenesis.

PMID- 19850843
TI  - Electrophysiological evidence of early functional damage in glaucoma and ocular
      hypertension.
AB  - PURPOSE: The quantification of early retinal ganglion cell damage in ocular
      hypertension and glaucoma. METHODS: Thirty subjects under treatment for open
      angle glaucoma, 23 subjects with ocular hypertension, and 28 healthy subjects in
      a control group were investigated by monocular pattern electroretinogram (ERG),
      L&M (long and medium wavelength) cone ERG, and S (short wavelength)-cone ERG. The
      diagnosis of glaucoma was based on masked assessment of digital stereoscopic
      optic nerve head images by three glaucoma specialists. The optic nerve head and
      retinal nerve fiber layer was assessed by scanning laser ophthalmoscopy and
      optical coherence tomography. RESULTS: All types of ERG had reduced mean
      amplitudes in ocular hypertension and open-angle glaucoma groups compared with
      the control group. In the ocular hypertension group, the N95 and the L&M-pathway
      photopic negative response (PhNR) were significantly attenuated (by 19% and 18%
      compared with the control group, respectively; by 30% and 22%, respectively, in
      the open-angle glaucoma group compared with the control group). In the subjects
      with open-angle glaucoma, the pattern ERG P50-N95 was found to be the most
      sensitive electrophysiological test, and the cup-disc area ratio, when examined
      by scanning laser ophthalmoscopy, was the most sensitive imaging parameter.
      Modest but not statistically significant correlations were found between the
      imaging and electrophysiologic parameters. CONCLUSIONS: With disc appearance used
      for the classification of open-angle glaucoma and ocular hypertension,
      significant electrophysiological losses were found in both conditions. The modest
      correlation between the structural and electrophysiological measures suggests
      that these assess different aspects of the pathologic process; electrophysiology
      can be used to quantify retinal ganglion cell dysfunction that occurs before cell
      death.

PMID- 19850845
TI  - Generation of light-sensitive photoreceptor phenotypes by genetic modification of
      human adult ocular stem cells with Crx.
AB  - PURPOSE: This study compared the effect of the transcription factor Crx (cone,
      rod homeobox) on the differentiation of human adult corneal (hCSC) and retinal
      (hRSC) stem cells into functional photoreceptors. METHODS: Stem cells isolated
      from postmortem human corneas and retinal ciliary bodies were maintained in serum
      free culture and genetically modified by electroporation to express exogenous
      epitope-tagged murine Crx. Expression of stem cell markers (Pax6, Oct3/4, and
      proliferating cell nuclear antigen [PCNA]), neuronal markers (nestin, neuron
      specific class III beta-tubulin, Map2 a/b, and neurofilament), and photoreceptor
      specific markers (rhodopsin, cyclic nucleotide-gated cation channel-3, blue-cone
      opsin, and beta-6-PDE) was evaluated by immunocytochemistry. A cGMP enzyme-linked
      immunoassay was used to assess phototransduction cascade activity by measurement
      of light-induced hydrolysis of cGMP. RESULTS: Expression of the stem cell markers
      of proliferation and pluripotency Pax6, PCNA, and Oct3/4 was decreased by
      exogenous Crx expression in both hCSCs and hRSCs. Correspondingly, the expression
      of the mature neuronal markers Map2 a/b and neurofilament was increased. Both
      hCSCs and hRSCs displayed photoreceptor-specific immunolabeling. However, light
      activated GMP hydrolysis was observed only in hRSCs after exogenous expression of
      Crx. CONCLUSIONS: The present study extends previous findings that exogenous Crx
      expression can promote differentiation of human retina-derived stem cells into
      light-sensitive photoreceptor phenotypes. Although Crx can induce human cornea
      derived stem cells to express photoreceptor-specific proteins, it does not seem
      to be sufficient to direct their differentiation into functional photoreceptors.
      Nevertheless, this study demonstrates that genetic modification of adult human
      retinal stem cells can cause differentiation into light-sensitive photoreceptor
      phenotypes.

PMID- 19850844
TI  - Expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of
      patients with dry eye syndrome.
AB  - PURPOSE: To investigate the expression of CXCL9, -10, -11, and CXCR3 in the tear
      film and ocular surface of patients with dry eye syndrome. METHODS: Thirty-three
      patients with dry eye (16 with and 17 without Sjogren's syndrome) and 15 control
      subjects were recruited. The concentrations of CXCL9, -10, and -11 in tears were
      measured with enzyme-linked immunosorbent assays. The correlation between
      chemokine levels and tear film and ocular surface parameters was analyzed. The
      expression of CXCL9, -10, -11, and CXCR3 in the conjunctiva was evaluated by
      using immunohistochemistry. Flow cytometry was performed to count CXCR3(+) cells
      and CXCR3(+)CD4(+) cells in the conjunctiva. RESULTS: The concentrations of
      CXCL9, -10, and -11 were 1,148 +/- 1,088, 24,338 +/- 8,706, and 853 +/- 334
      pg/mL, in the patients with dry eye, and 272 +/- 269 (P = 0.01), 18,149 +/- 5,266
      (P = 0.02), and 486 +/- 175 (P < 0.01) pg/mL in the control subjects,
      respectively. The concentrations significantly increased in tears of the patients
      with Sjogren's syndrome compared with those of the patients with non-Sjogren's
      dry eye (P < 0.05). CXCL10 levels correlated significantly with basal tear
      secretion, and CXCL11 levels correlated significantly with basal tear secretion,
      tear clearance rate, keratoepitheliopathy score, and goblet cell density (P <
      0.05). Staining for CXCL9, -10, -11, and CXCR3 increased in patients with dry
      eye, especially in the patients with Sjogren's syndrome. Flow cytometry
      demonstrated an increased number of CXCR3(+) and CXCR3(+)CD4(+) cells in all the
      patients with dry eye. CONCLUSIONS: Expression of CXCL9, -10, -11, and CXCR3
      increased in the tear film and ocular surface of patients with dry eye syndrome,
      especially in those with Sjogren's syndrome. CXCL11 levels correlated
      significantly with various tear film and ocular surface parameters.
      (ClinicalTrials.gov number, NCT00991679.).

PMID- 19850846
TI  - Basic quantitative assessment of visual performance in patients with very low
      vision.
AB  - PURPOSE: A variety of approaches to developing visual prostheses are being
      pursued: subretinal, epiretinal, via the optic nerve, or via the visual cortex.
      This report presents a method of comparing their efficacy at genuinely improving
      visual function, starting at no light perception (NLP). METHODS: A test battery
      (a computer program, Basic Assessment of Light and Motion [BaLM]) was developed
      in four basic visual dimensions: (1) light perception (light/no light), with an
      unstructured large-field stimulus; (2) temporal resolution, with single versus
      double flash discrimination; (3) localization of light, where a wedge extends
      from the center into four possible directions; and (4) motion, with a coarse
      pattern moving in one of four directions. Two- or four-alternative, forced-choice
      paradigms were used. The participants' responses were self-paced and delivered
      with a keypad. RESULTS: The feasibility of the BaLM was tested in 73 eyes of 51
      patients with low vision. The light and time test modules discriminated between
      NLP and light perception (LP). The localization and motion modules showed no
      significant response for NLP but discriminated between LP and hand movement (HM).
      All four modules reached their ceilings in the acuity categories higher than HM.
      CONCLUSIONS: BaLM results systematically differed between the very-low-acuity
      categories NLP, LP, and HM. Light and time yielded similar results, as did
      localization and motion; still, for assessing the visual prostheses with
      differing temporal characteristics, they are not redundant. The results suggest
      that this simple test battery provides a quantitative assessment of visual
      function in the very-low-vision range from NLP to HM.

PMID- 19850847
TI  - Endothelial morphometry by image analysis of corneas organ cultured at 31 degrees
      C.
AB  - PURPOSE: To determine the factors influencing endothelial morphometry by using
      image analysis of corneas stored in organ culture to determine the coefficient of
      variation (CV) in cell area and percentage of hexagonal cells. METHODS: The
      endothelia of 505 of the 559 corneas consecutively stored at the eye bank were
      routinely analyzed with Sambacornea image-analysis software (ver. 1.2.10; Tribvn,
      Chatillon, France) on three large-field images of 750 x 1000 microm, obtained
      after osmotic dilation of the intercellular spaces with 0.9% sodium chloride.
      Analysis was performed on at least 300 cells. The quality of the three-image set
      was graded poor, average, or good by an independent observer. The studied
      parameters were donor age and sex, lens status, storage time, and intrinsic
      quality of captured images. Statistics were analyzed by nonparametric tests.
      RESULTS: Image analysis was possible for 504 of the 505 assessed corneas. Donor
      age correlated significantly with endothelial cell density (ECD; r = -0.343), CV
      (r = 0.221), and hexagonality (r = -0.314; P < 0.001 for the three). Image
      quality significantly influenced these three parameters. ECD and hexagonality
      decreased parallel to image quality, whereas the CV increased. In the 258 corneas
      assessed twice (on average, at day [D] +4, then D +14) ECD, CV, and hexagonality
      decreased during storage. CONCLUSIONS: Despite the sometimes mediocre quality of
      the transmitted light microscopy images, endothelial parameters supplied by the
      analyzer were clinically reliable, since variations similar to those long known
      in specular microscopy were found. Endothelial morphometry (CV and hexagonality)
      is likely to provide further information on the endothelial function of the graft
      tissue, perhaps particularly for grafts of borderline ECD, close to the discard
      threshold.

PMID- 19850848
TI  - Effect of dorzolamide and timolol on ocular pressure: blood flow relationship in
      patients with primary open-angle glaucoma and ocular hypertension.
AB  - PURPOSE: The authors have reported previously that a study population, consisting
      of patients with glaucoma and ocular hypertension, is characterized by an
      impaired association between ocular blood flow parameters and systemic blood
      pressure, indicative of abnormal autoregulation. Here they report on the effects
      of dorzolamide and timolol on ocular pressure/flow relationships to test the
      hypothesis that these drugs improve autoregulation. METHODS: One hundred forty
      patients with primary open-angle glaucoma or ocular hypertension were included in
      a clinical trial in a controlled, randomized double-masked study in two parallel
      groups. Seventy patients were randomly assigned to receive timolol, and 70
      patients were randomly assigned to receive dorzolamide for a 6-month period.
      Scanning laser Doppler flowmetry was used to measure blood flow in the temporal
      neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood
      flow was assessed using laser interferometric measurement of fundus pulsation
      amplitude. The association between blood flow parameters and systemic blood
      pressure was compared before and after the 6-month treatment period. RESULTS:
      Before treatment a significant association was observed between ocular blood flow
      parameters and systemic blood pressure in both parallel groups (r = 0.23-0.42).
      All regression lines between ocular hemodynamic parameters and systemic blood
      pressure were less steep after treatment with either dorzolamide or timolol (r =
      0.03-0.24). CONCLUSIONS: The present study indicates that intraocular pressure
      reduction with timolol or dorzolamide is associated with normalization of the
      ocular pressure/flow relationship. Whether this is related to the beneficial
      effects of IOP-lowering therapy in glaucoma remains to be established.
      (ClinicalTrials.gov number, NCT00991822.).

PMID- 19850849
TI  - DUF1220 domains, cognitive disease, and human brain evolution.
AB  - We have established that human genome sequences encoding a novel protein domain,
      DUF1220, show a dramatically elevated copy number in the human lineage (>200
      copies in humans vs. 1 in mouse/rat) and may be important to human evolutionary
      adaptation. Copy-number variations (CNVs) in the 1q21.1 region, where most
      DUF1220 sequences map, have now been implicated in numerous diseases associated
      with cognitive dysfunction, including autism, autism spectrum disorder, mental
      retardation, schizophrenia, microcephaly, and macrocephaly. We report here that
      these disease-related 1q21.1 CNVs either encompass or are directly flanked by
      DUF1220 sequences and exhibit a dosage-related correlation with human brain size.
      Microcephaly-producing 1q21.1 CNVs are deletions, whereas macrocephaly-producing
      1q21.1 CNVs are duplications. Similarly, 1q21.1 deletions and smaller brain size
      are linked with schizophrenia, whereas 1q21.1 duplications and larger brain size
      are associated with autism. Interestingly, these two diseases are thought to be
      phenotypic opposites. These data suggest a model which proposes that (1) DUF1220
      domain copy number may be involved in influencing human brain size and (2) the
      evolutionary advantage of rapidly increasing DUF1220 copy number in the human
      lineage has resulted in favoring retention of the high genomic instability of the
      1q21.1 region, which, in turn, has precipitated a spectrum of recurrent human
      brain and developmental disorders.

PMID- 19850850
TI  - Evo-devo and the evolution of social behavior: brain gene expression analyses in
      social insects.
AB  - Studies of genes and social behavior, aided by new genomic resources, are coming
      of age. Here, we show how some of the insights that have emerged from research on
      the evolution of development (evo-devo) also provide a useful framework for
      studying the evolution of social behavior at the molecular level. These insights
      include co-opting old genes for new functions, phenotypic modularity, genetic
      tool kits, the importance of gene regulation in evolutionary change, and the
      influences of some genes over multiple timescales. We next outline a few
      differences between development and behavior that pose challenges for an evo-devo
      approach to behavior. For the remainder of this chapter, we review several
      studies that illustrate the relevance of evo-devo insights to our understanding
      of the evolution of behaviors related to eusociality in the insect societies.

PMID- 19850851
TI  - Evolution of biological catalysis: ribozyme to RNP enzyme.
AB  - The enzymes that perform biological catalysis in contemporary organisms are
      usually proteins, occasionally ribonucleoprotein (RNP) complexes, and in rare
      instances pure RNA (ribozymes). Because RNA can serve as both an informational
      molecule and a biocatalyst, it has been attractive to consider a primordial RNA
      World in which RNA enzymes catalyzed the replication of RNA genomes and an array
      of other metabolic steps, before the advent of protein enzymes and DNA genomes.
      By what pathways, then, did the RNA World evolve to the present state? Here, I
      describe plausible pathways for the evolution of biological catalysis, with
      special emphasis on the origin of RNP enzymes. Recent findings support the
      argument that RNP enzymes are not undergoing extinction, but instead, they are
      continuing to evolve and to elaborate new functions.

PMID- 19850852
TI  - Strengths, weaknesses, opportunities and threats of the pig health monitoring
      systems used in England.
AB  - Several systems are being used in England to record information about the health
      of pigs. The British Pig Health Scheme (BPHS), the National Animal Disease
      Information System (NADIS), the Zoonoses Action Plan (ZAP) for Salmonella and the
      Veterinary Investigation Diagnosis Analysis (VIDA) system have been assessed to
      make recommendations for their future separate or joint development. The
      structure, organisation, processes, data quality, dissemination, utilisation and
      acceptance of each system have been assessed. Information was extracted from
      documents and websites, and informal interviews were conducted with technical
      experts and stakeholders. The systems covered a broad range of objectives, used
      variable approaches and operated at very different scales and budgets. There was
      a high level of awareness and involvement by the industry. Common weaknesses of
      the systems were the lack of in-depth quantitative analysis of the data, the lack
      of assessment of each system's impact, and the unknown level of bias as a result
      of the voluntary or selective participation in them.

PMID- 19850853
TI  - Comparison of total calcium, ionised calcium and albumin concentrations in the
      plasma of captive tortoises (Testudo species).
AB  - Plasma total calcium, ionised calcium and albumin levels in Hermann's tortoises
      (Testudo hermanni), spur-thighed tortoises (Testudo graeca), marginated tortoises
      (Testudo marginata) and Horsfield's tortoises (Testudo horsfieldi) were
      investigated. The animals were captive adults maintained under natural unfiltered
      sunlight in the UK with no dietary sources of cholecalciferol. Analysis of total
      calcium data showed statistically significant seasonal elevations in females in
      August compared with March (P=0.003), and statistically significant elevations in
      females compared with males at all sampling points (March P=0.036, June P=0.003
      and August P<0.0001). These differences in values became more prominent as the
      summer progressed. Albumin values did not appear significantly affected by
      season. However, males had significantly higher albumin levels than females in
      the August samples. A correlation between total calcium and ionised calcium was
      confirmed but there was no correlation between total calcium and albumin values.
      Total calcium levels were a poor indication of ionised calcium levels, which
      constituted between 18 and 57 per cent of the total calcium value.

PMID- 19850854
TI  - Collection and analysis of breath and breath condensate exhaled by feral pigeons
      (Columba livia) and chickens (Gallus domesticus).
AB  - Samples of exhaled breath and breath condensate were collected from 20 feral
      pigeons (Columba livia) while they were anaesthetised and intubated, and when
      they were kept unanaesthetised in an acrylic box. Samples were also collected
      from six chickens (Gallus domesticus) while they were kept in an acrylic box. The
      samples were analysed for pH, nitric oxide (NO), hydrogen peroxide and
      leukotriene B4. The volume of condensate collected from the pigeons was
      independent of bodyweight and significantly more (1.66 [0.64] ml/kg) was obtained
      while they were in the acrylic box than when they were intubated (0.87 [0.32]
      ml/kg). The mean volume collected from the chickens was 0.15 (0.06) ml/kg. Cooled
      samples had higher concentrations of NO than uncooled samples. The pH of the
      samples of condensate collected from birds in the acrylic box were significantly
      higher (7.9 [0.3]) than those from the intubated birds (5.3 [0.1]), and samples
      from the chickens had significantly higher pH values than samples from the
      pigeons (8.2 [0.2] v 7.9 [0.3]).

PMID- 19850855
TI  - Prevalence of EHV-1 in adult horses transported over long distances.

PMID- 19850856
TI  - Risk factors for abortion in cattle herds in Algeria.

PMID- 19850857
TI  - Repair of hock fractures in racing greyhounds.

PMID- 19850858
TI  - Investigations into suspected white-nose syndrome in two bat species in Somerset.

PMID- 19850859
TI  - Changes to the bovine TB surveillance and control programme in England.

PMID- 19850860
TI  - PCR detection of adenovirus in grey squirrels on Anglesey.

PMID- 19850861
TI  - Screening patients in busy hospital-based HIV care centers for hazardous and
      harmful drinking patterns: the identification of an optimal screening tool.
AB  - Because many HIV care providers fail to detect patients' hazardous drinking, we
      examined the potential use of the AUDIT-C, the first 3 of the 10 items comprising
      the Alcohol Use Disorders Identification Test (AUDIT), to efficiently screen
      patients for alcohol abuse. To perform this examination, we used Item Response
      Theory (IRT) involving individual AUDIT items and AUDIT instruments completed by
      patients (N = 400) at a Designated AIDS Center (DAC) in New York City. At various
      AUDIT-C cutoff scores, specificities and sensitivities were then examined using
      the AUDIT as a ''gold standard.'' For cutoff scores on the AUDIT from 4 to 8,
      cutoff scores on the AUDIT-C of 3 and 4, respectively, resulted in sensitivities
      between .94-.98 and .81-.89, respectively, and specificities between .82-.91 and
      .91-1.0, respectively. In busy HIV care centers, the AUDIT-C with cutoff scores
      of 3 or 4 is a reasonable alternative to the full AUDIT as an alcohol screening
      instrument.

PMID- 19850863
TI  - Letting students be innovative! Using mini-grants to fund student-designed
      HIV/AIDS education.
AB  - This article describes a project designed to use student leaders to increase the
      awareness of HIV/AIDS among college students. Student organizations apply for a
      competitive mini-grant that is used to increase their members' knowledge level
      about HIV/AIDS and increase the likelihood of individuals' practicing behaviors
      that would reduce the risk of transmission or contraction. Four student
      organizations receive funds to design a unique HIV/ AIDS prevention intervention
      that match its members' needs for a total of 126 individuals receiving HIV/AIDS
      education. An evaluation indicates positive behavioral intentions related to
      sexual communication and safer sex practices. Moreover, the majority of
      participants report the education received as relevant and applicable. The
      methods, intervention applications, and benefits to using an award competition to
      deliver HIV prevention education to college students in a nontraditional and
      innovative approach are detailed within this article.

PMID- 19850864
TI  - Hotspots of GPI-anchored proteins and integrin nanoclusters function as
      nucleation sites for cell adhesion.
AB  - Recruitment of receptor proteins to lipid rafts has been proposed as an important
      mechanism to regulate their cellular function. In particular, rafts have been
      implicated in regulation of integrin-mediated cell adhesion, although the
      underlying mechanism remains elusive. We used single-molecule near-field optical
      microscopy (NSOM) with localization accuracy of approximately 3 nm, to capture
      the spatio-functional relationship between the integrin LFA-1 and raft components
      (GPI-APs) on immune cells. Dual color nanoscale imaging revealed the existence of
      a nanodomain GPI-AP subpopulation that further concentrated in regions smaller
      than 250 nm, suggesting a hierarchical prearrangement of GPI-APs on resting
      monocytes. We previously demonstrated that in quiescent monocytes, LFA-1
      preorganizes in nanoclusters. We now show that integrin nanoclusters are
      spatially different but reside proximal to GPI-AP nanodomains, forming hotspots
      on the cell surface. Ligand-mediated integrin activation resulted in an
      interconversion from monomers to nanodomains of GPI-APs and the generation of
      nascent adhesion sites where integrin and GPI-APs colocalized at the nanoscale.
      Cholesterol depletion significantly affected the reciprocal distribution pattern
      of LFA-1 and GPI-APs in the resting state, and LFA-1 adhesion to its ligand. As
      such, our data demonstrate the existence of nanoplatforms as essential
      intermediates in nascent cell adhesion. Since raft association with a variety of
      membrane proteins other than LFA-1 has been documented, we propose that hotspots
      regions enriched with raft components and functional receptors may constitute a
      prototype of nanoscale inter-receptor assembly and correspond to a generic
      mechanism to offer cells with privileged areas for rapid cellular function and
      responses to the outside world.

PMID- 19850865
TI  - Ligand migration through the internal hydrophobic cavities in human neuroglobin.
AB  - Neuroglobin (Ngb), a member of the globin superfamily, was found in the brain of
      vertebrates and is suggested to play a neuroprotective function under hypoxic
      conditions by scavenging nitrogen monoxide (NO) through a dioxygenase activity.
      In order for such a reaction to efficiently take place and to minimize the
      release of reactive intermediates in the cytosol, the cosubstrates O(2) and NO
      and other unstable reaction intermediates should bind sequentially to docking
      sites in the protein matrix. We have characterized the accessibility of these
      sites by analyzing the geminate CO rebinding kinetics to the heme moiety observed
      upon nanosecond flash photolysis of the Ngb-CO complex encapsulated in silica
      gels. The geminate rebinding phase showed a remarkable complexity, revealing the
      presence of a system of secondary docking sites where ligands are stored for
      hundreds of microseconds. Most kinetics steps display little temperature
      dependence, demonstrating that ligands can easily migrate through the cavities,
      except for the slowest reaction intermediate, possibly reflecting a structural
      conformational change reshaping the system of cavities. This conformational
      change is unrelated with distal His E7 binding to the heme, as it persists for
      the HE7L mutant. Overall, data are consistent with the presence of a discrete
      system of docking sites, possibly acting as reservoirs for the putative
      cosubstrates and for other reactive species involved in the physiologically
      relevant reaction.

PMID- 19850866
TI  - Helical structure and stability in human apolipoprotein A-I by hydrogen exchange
      and mass spectrometry.
AB  - Apolipoprotein A-I (apoA-I) stabilizes anti-atherogenic high density lipoprotein
      particles (HDL) in the circulation and governs their biogenesis, metabolism, and
      functional interactions. To decipher these important structure-function
      relationships, it will be necessary to understand the structure, stability, and
      plasticity of the apoA-I molecule. Biophysical studies show that lipid-free apoA
      I contains a large amount of alpha-helical structure but the location of this
      structure and its properties are not established. We used hydrogen-deuterium
      exchange coupled with a fragmentation-separation method and mass spectrometric
      analysis to study human lipid-free apoA-I in its physiologically pertinent
      monomeric form. The acquisition of approximately 100 overlapping peptide
      fragments that redundantly cover the 243-residue apoA-I polypeptide made it
      possible to define the positions and stabilities of helical segments and to draw
      inferences about their interactions and dynamic properties. Residues 7-44, 54-65,
      70-78, 81-115, and 147-178 form alpha-helices, accounting for a helical content
      of 48 +/- 3%, in agreement with circular dichroism measurements (49%). At 3 to 5
      kcal/mol in free energy of stabilization, the helices are far more stable than
      could be achieved in isolation, indicating mutually stabilizing helix bundle
      interactions. However the helical structure is dynamic, unfolding and refolding
      in seconds, allowing facile apoA-I reorganization during HDL particle formation
      and remodeling.

PMID- 19850867
TI  - Problems with burden-sharing proposal among one billion high emitters.

PMID- 19850868
TI  - Do nonlinear temperature effects indicate severe damages to US crop yields under
      climate change?

PMID- 19850869
TI  - Differential induction of apoptosis in HER2 and EGFR addicted cancers following
      PI3K inhibition.
AB  - Non-small cell lung cancers with activating mutations in the epidermal growth
      factor receptor (EGFR) are highly responsive to EGFR tyrosine kinase inhibitors
      (TKIs), such as gefitinib and erlotinib. Such cancers are "addicted" to EGFR, and
      treatment with a TKI invariably leads to down-regulation of the PI3K-AKT-mTOR and
      MEK-ERK signaling pathways, resulting in apoptosis. Using a dual PI3K-mTOR
      inhibitor, NVP-BEZ235, we evaluated whether PI3K-mTOR inhibition alone induced
      apoptosis in these cancers. In contrast to HER2-amplified breast cancers, we
      found that PI3K-mTOR inhibition did not promote substantial apoptosis in the EGFR
      mutant lung cancers. However, blocking both PI3K-mTOR and MEK simultaneously led
      to apoptosis to similar levels as the EGFR TKIs, suggesting that down-regulation
      of these pathways may account for much of the apoptosis promoted by EGFR
      inhibition. In EGFR mutant lung cancers, down-regulation of both intracellular
      pathways converged on the BH3 family of proteins regulating apoptosis. PI3K
      inhibition led to down-regulation of Mcl-1, and MEK inhibition led to up
      regulation of BIM. In fact, down-regulation of Mcl-1 by siRNA was sufficient to
      sensitize these cancers to single-agent MEK inhibitors. Surprisingly, an AKT
      inhibitor did not decrease Mcl-1 levels, and when combined with MEK inhibitors,
      failed to induce apoptosis. Importantly, we observed that the combination of PI3K
      mTOR and MEK inhibitors effectively shrunk tumors in a transgenic and xenograft
      model of EGFR T790M-L858R cancers. These data indicate simultaneous inhibition of
      PI3K-mTOR and MEK signaling is an effective strategy for treating EGFR mutant
      lung cancers, including those with acquired resistance to EGFR TKIs.

PMID- 19850870
TI  - Genetic ablation of retinal pigment epithelial cells reveals the adaptive
      response of the epithelium and impact on photoreceptors.
AB  - The retinal pigment epithelium (RPE) plays a critical role in the maintenance of
      the outer retina. RPE cell death or dysfunction drives the pathophysiology of
      many retinal diseases, but the physiological response of the retina to RPE cell
      loss is poorly understood, mainly because of the absence of suitable experimental
      models. Here, we generated a transgenic mouse in which an inducible Cre
      recombinase is expressed exclusively in the RPE under the control of the
      monocarboxylate transporter 3 gene promoter (RPE(CreER)). This was crossed with a
      transgenic mouse harboring a diphtheria toxin A (DTA) chain gene rendered
      transcriptionally silent by a floxed stop sequence. We show that activation of
      DTA in the double transgenic mouse (RPE(CreER)/DTA) led to 60-80% RPE cell death,
      with surviving cells maintaining the integrity of the monolayer by increasing
      their size. Despite the apparent morphological normality of the enlarged RPE
      cells in the RPE(CreER)/DTA mice, functional analysis revealed significant
      deficits on electroretinography, and retinal histopathology showed regions of
      photoreceptor rosetting and degeneration although with retention of a normal
      vascular network. Our study reveals that whilst the RPE monolayer has a
      remarkable intrinsic capacity to cope with cellular attrition, specific aspects
      of RPE multifunctionality essential for photoreceptor survival are compromised.
      The RPE(CreER)/DTA mouse offers advantages over models that employ chemical or
      mechanical strategies to kill RPE cells, and should be useful for the development
      and evaluation of RPE-based therapies, such as stem cell transplantation.

PMID- 19850871
TI  - A perinuclear actin cap regulates nuclear shape.
AB  - Defects in nuclear morphology often correlate with the onset of disease,
      including cancer, progeria, cardiomyopathy, and muscular dystrophy. However, the
      mechanism by which a cell controls its nuclear shape is unknown. Here, we use
      adhesive micropatterned surfaces to control the overall shape of fibroblasts and
      find that the shape of the nucleus is tightly regulated by the underlying cell
      adhesion geometry. We found that this regulation occurs through a dome-like actin
      cap that covers the top of the nucleus. This cap is composed of contractile actin
      filament bundles containing phosphorylated myosin, which form a highly organized,
      dynamic, and oriented structure in a wide variety of cells. The perinuclear actin
      cap is specifically disorganized or eliminated by inhibition of actomyosin
      contractility and rupture of the LINC complexes, which connect the nucleus to the
      actin cap. The organization of this actin cap and its nuclear shape-determining
      function are disrupted in cells from mouse models of accelerated aging (progeria)
      and muscular dystrophy with distorted nuclei caused by alterations of A-type
      lamins. These results highlight the interplay between cell shape, nuclear shape,
      and cell adhesion mediated by the perinuclear actin cap.

PMID- 19850872
TI  - During its nuclear phase the multifunctional regulatory protein ICP0 undergoes
      proteolytic cleavage characteristic of polyproteins.
AB  - ICP0 is a multifunctional herpes simplex virus protein known primarily as a
      promiscuous transactivator. In the course of productive infection, it is
      localized during the first 5-7 h in the nucleus and later in the cytoplasm. In
      the nucleus, its primary activities are to suppress the silencing of viral DNA by
      host proteins, activate cdk4 through recruitment of cyclin D3 to the sites of
      formation of replication compartments, and degrade several cellular proteins
      including PML and Sp100, key components of the ND10 nuclear bodies. ICP0 is not
      translocated to the cytoplasm in cells infected with mutants incapable of
      performing these tasks. We report the unexpected finding that ICP0 is cleaved
      into several discrete polypeptides by a proteasome-independent process. The
      products of this cleavage accumulate in cells infected with ICP0 mutants
      incapable of degrading PML and therefore are retained in the nucleus. In the
      second step, the products of the initial cleavage of wild-type virus-infected
      cells are themselves subject to proteasome-dependent degradation. The average
      half life of intact ICP0 during the nuclear phase is approximately 1 h. The
      proteasome-independent cleavage products are no longer detected at late times
      corresponding to the cytoplasmic phase of ICP0. The results are consistent with
      the hypothesis that the cleavage products of ICP0 function in topologically
      distinct domains during its nuclear phase.

PMID- 19850873
TI  - Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease.
AB  - Constitutive androstane receptor CAR (NR1I3) has been identified as a central
      mediator of coordinate responses to xenobiotic and endobiotic stress. Here we use
      leptin-deficient mice (ob/ob) and ob/ob, CAR(-/-) double mutant mice to identify
      a metabolic role of CAR in type 2 diabetes. Activation of CAR significantly
      reduces serum glucose levels and improves glucose tolerance and insulin
      sensitivity. Gene expression analyses and hyperinsulinemic euglycemic clamp
      results suggest that CAR activation ameliorates hyperglycemia by suppressing
      glucose production and stimulating glucose uptake and usage in the liver. In
      addition, CAR activation dramatically improves fatty liver by both inhibition of
      hepatic lipogenesis and induction of beta-oxidation. We conclude that CAR
      activation improves type 2 diabetes, and that these actions of CAR suggest
      therapeutic approaches to the disease.

PMID- 19850874
TI  - Neural representation of time in cortico-basal ganglia circuits.
AB  - Encoding time is universally required for learning and structuring motor and
      cognitive actions, but how the brain keeps track of time is still not understood.
      We searched for time representations in cortico-basal ganglia circuits by
      recording from thousands of neurons in the prefrontal cortex and striatum of
      macaque monkeys performing a routine visuomotor task. We found that a subset of
      neurons exhibited time-stamp encoding strikingly similar to that required by
      models of reinforcement-based learning: They responded with spike activity peaks
      that were distributed at different time delays after single task events.
      Moreover, the temporal evolution of the population activity allowed robust
      decoding of task time by perceptron models. We suggest that time information can
      emerge as a byproduct of event coding in cortico-basal ganglia circuits and can
      serve as a critical infrastructure for behavioral learning and performance.

PMID- 19850875
TI  - Spatiotemporally separable Shh domains in the midbrain define distinct
      dopaminergic progenitor pools.
AB  - Midbrain dopamine neurons (mDA) are important regulators of diverse physiological
      functions, including movement, attention, and reward behaviors. Accordingly,
      aberrant function of dopamine neurons underlies a wide spectrum of disorders,
      such as Parkinson's disease (PD), dystonia, and schizophrenia. The distinct
      functions of the dopamine system are carried out by neuroanatomically discrete
      subgroups of dopamine neurons, which differ in gene expression, axonal
      projections, and susceptibility in PD. The developmental underpinnings of this
      heterogeneity are undefined. We have recently shown that in the embryonic CNS,
      mDA originate from the midbrain floor plate, a ventral midline structure that is
      operationally defined by the expression of the molecule Shh. Here, we develop
      these findings to reveal that in the embryonic midbrain, the spatiotemporally
      dynamic Shh domain defines multiple progenitor pools. We deduce 3 distinct
      progenitor pools, medial, intermediate, and lateral, which contribute to
      different mDA clusters. The earliest progenitors to express Shh, here referred to
      as the medial pool, contributes neurons to the rostral linear nucleus and mDA of
      the ventral tegmental area/interfascicular regions, but remarkably, little to the
      substantia nigra pars compacta. The intermediate Shh+ progenitors give rise to
      neurons of all dopaminergic nuclei, including the SNpc. The last and lateral pool
      of Shh+ progenitors generates a cohort that populates the red nucleus, Edinger
      Westphal nucleus, and supraoculomotor nucleus and cap. Subsequently, these
      lateral Shh+ progenitors produce mDA. This refined ontogenetic definition will
      expand understanding of dopamine neuron biology and selective susceptibility, and
      will impact stem cell-derived therapies and models for PD.

PMID- 19850876
TI  - Interaction of an autotransporter passenger domain with BamA during its
      translocation across the bacterial outer membrane.
AB  - Autotransporters are a superfamily of virulence factors produced by Gram-negative
      bacteria consisting of a large N-terminal extracellular domain ("passenger
      domain") and a C-terminal beta barrel domain ("beta domain"). The mechanism by
      which the passenger domain is translocated across the outer membrane (OM) is
      unknown. Here we show that the insertion of a small linker into the passenger
      domain of the Escherichia coli O157:H7 autotransporter EspP effectively creates a
      translocation intermediate by transiently stalling translocation near the site of
      the insertion. Using a site-specific photocrosslinking approach, we found that
      residues adjacent to the stall point interact with BamA, a component of a
      heterooligomeric complex (Bam complex) that catalyzes OM protein assembly, and
      that residues closer to the EspP N terminus interact with the periplasmic
      chaperones SurA and Skp. The EspP-BamA interaction was short-lived and could be
      detected only when passenger domain translocation was stalled. These results
      support a model in which molecular chaperones prevent misfolding of the passenger
      domain before its secretion and the Bam complex catalyzes both the integration of
      the beta domain into the OM and the translocation of the passenger domain across
      the OM in a C- to N-terminal direction.

PMID- 19850877
TI  - Homozygous loss of BHD causes early embryonic lethality and kidney tumor
      development with activation of mTORC1 and mTORC2.
AB  - Germline mutations in the BHD/FLCN tumor suppressor gene predispose patients to
      develop renal tumors in the hamartoma syndrome, Birt-Hogg-Dube (BHD). BHD encodes
      folliculin, a protein with unknown function that may interact with the energy-
      and nutrient-sensing AMPK-mTOR signaling pathways. To clarify BHD function in the
      mouse, we generated a BHD knockout mouse model. BHD homozygous null (BHD(d/d))
      mice displayed early embryonic lethality at E5.5-E6.5, showing defects in the
      visceral endoderm. BHD heterozygous knockout (BHDd(/+)) mice appeared normal at
      birth but developed kidney cysts and solid tumors as they aged (median kidney
      lesion-free survival = 23 months, median tumor-free survival = 25 months). As
      observed in human BHD kidney tumors, three different histologic types of kidney
      tumors developed in BHD(d/+) mice including oncocytic hybrid, oncocytoma, and
      clear cell with concomitant loss of heterozygosity (LOH), supporting a tumor
      suppressor function for BHD in the mouse. The PI3K-AKT pathway was activated in
      both human BHD renal tumors and kidney tumors in BHD(d/+) mice. Interestingly,
      total AKT protein was elevated in kidney tumors compared to normal kidney tissue,
      but without increased levels of AKT mRNA, suggesting that AKT may be regulated by
      folliculin through post translational or post-transcriptional modification.
      Finally, BHD inactivation led to both mTORC1 and mTORC2 activation in kidney
      tumors from BHD(d/+) mice and human BHD patients. These data support a role for
      PI3K-AKT pathway activation in kidney tumor formation caused by loss of BHD and
      suggest that inhibitors of both mTORC1 and mTORC2 may be effective as potential
      therapeutic agents for BHD-associated kidney cancer.

PMID- 19850878
TI  - Pharmacological modulation of subliminal learning in Parkinson's and Tourette's
      syndromes.
AB  - Theories of instrumental learning aim to elucidate the mechanisms that integrate
      success and failure to improve future decisions. One computational solution
      consists of updating the value of choices in proportion to reward prediction
      errors, which are potentially encoded in dopamine signals. Accordingly, drugs
      that modulate dopamine transmission were shown to impact instrumental learning
      performance. However, whether these drugs act on conscious or subconscious
      learning processes remains unclear. To address this issue, we examined the
      effects of dopamine-related medications in a subliminal instrumental learning
      paradigm. To assess generality of dopamine implication, we tested both dopamine
      enhancers in Parkinson's disease (PD) and dopamine blockers in Tourette's
      syndrome (TS). During the task, patients had to learn from monetary outcomes the
      expected value of a risky choice. The different outcomes (rewards and
      punishments) were announced by visual cues, which were masked such that patients
      could not consciously perceive them. Boosting dopamine transmission in PD
      patients improved reward learning but worsened punishment avoidance. Conversely,
      blocking dopamine transmission in TS patients favored punishment avoidance but
      impaired reward seeking. These results thus extend previous findings in PD to
      subliminal situations and to another pathological condition, TS. More generally,
      they suggest that pharmacological manipulation of dopamine transmission can
      subconsciously drive us to either get more rewards or avoid more punishments.

PMID- 19850879
TI  - Highly specialized microbial diversity in hyper-arid polar desert.
AB  - The McMurdo Dry Valleys in Antarctica are a cold hyperarid polar desert that
      present extreme challenges to life. Here, we report a culture-independent survey
      of multidomain microbial biodiversity in McKelvey Valley, a pristine example of
      the coldest desert on Earth. We demonstrate that life has adapted to form highly
      specialized communities in distinct lithic niches occurring concomitantly within
      this terrain. Endoliths and chasmoliths in sandstone displayed greatest
      diversity, whereas soil was relatively depauperate and lacked a significant
      photoautotrophic component, apart from isolated islands of hypolithic
      cyanobacterial colonization on quartz rocks in soil contact. Communities
      supported previously unreported polar bacteria and fungi, but archaea were absent
      from all niches. Lithic community structure did not vary significantly on a
      landscape scale and stochastic moisture input due to snowmelt resulted in
      increases in colonization frequency without significantly affecting diversity.
      The findings show that biodiversity near the cold-arid limit for life is more
      complex than previously appreciated, but communities lack variability probably
      due to the high selective pressures of this extreme environment.

PMID- 19850880
TI  - Myocardin is required for cardiomyocyte survival and maintenance of heart
      function.
AB  - Despite intense investigation over the past century, the molecular mechanisms
      that regulate maintenance and adaptation of the heart during postnatal
      development are poorly understood. Myocardin is a remarkably potent
      transcriptional coactivator expressed exclusively in cardiac myocytes and smooth
      muscle cells during postnatal development. Here we show that myocardin is
      required for maintenance of cardiomyocyte structure and sarcomeric organization
      and that cell-autonomous loss of myocardin in cardiac myocytes triggers
      programmed cell death. Mice harboring a cardiomyocyte-restricted null mutation in
      the myocardin gene (Myocd) develop dilated cardiomyopathy and succumb from heart
      failure within a year. Remarkably, ablation of the Myocd gene in the adult heart
      leads to the rapid-onset of heart failure, dilated cardiomyopathy, and death
      within a week. Myocd gene ablation is accompanied by dissolution of sarcomeric
      organization, disruption of the intercalated disc, and cell-autonomous loss of
      cardiomyocytes via apoptosis. Expression of myocardin/serum response factor
      regulated myofibrillar genes is extinguished, or profoundly attenuated, in
      myocardin-deficient hearts. Conversely, proapoptotic factors are induced and
      activated in myocardin-deficient hearts. We conclude that the transcriptional
      coactivator myocardin is required for maintenance of heart function and
      ultimately cardiomyocyte survival.

PMID- 19850882
TI  - Pivotal Advance: Pharmacological manipulation of inflammation resolution during
      spontaneously resolving tissue neutrophilia in the zebrafish.
AB  - Zebrafish are a unique model for pharmacological manipulation of physiological
      processes such as inflammation; they are small and permeable to many small
      molecular compounds, and being transparent, they permit the visualization and
      quantitation of the inflammatory response by observation of transgenically
      labeled inflammatory cell populations. Using a transgenic line specifically
      labeling neutrophils in vivo (mpx:GFP), we studied the effects of a range of
      pharmacological agents on the resolution of inflammation in vivo. These agents
      were selected for their ability to modulate neutrophil function and lifespan in
      human neutrophils in vitro. Agents delaying neutrophil apoptosis (LPS, dbcAMP,
      and several caspase inhibitors) all lead to a delay in resolution of neutrophilic
      inflammation. Reciprocally, pyocyanin and roscovitine (inducers of neutrophil
      apoptosis) lead to reduced neutrophil numbers. The occurrence of apoptosis was
      observed by time-lapse analysis and confirmed by dual staining for neutrophil
      specific mpx activity (TSA staining) and an apoptotic marker (TUNEL). During
      inflammation, macrophages follow neutrophils into the inflamed site, and
      TUNEL/TSA dual-positive material can be demonstrated within macrophages,
      consistent with their uptake of apoptotic neutrophils. This model has several
      advantages over mammalian models and lends itself to the study of pharmaceutical
      agents modulating inflammation.

PMID- 19850884
TI  - Reduced transcript stabilization restricts TNF-alpha expression in RAW264.7
      macrophages infected with pathogenic mycobacteria: evidence for an involvement of
      lipomannan.
AB  - Despite the critical role that TNF-alpha plays in the containment of
      mycobacterial infection, the mechanisms involved in regulation of its expression
      by mycobacteria are poorly defined. We addressed this question by studying MAP,
      which causes a chronic enteritis in ruminants and is linked to human Crohn's
      disease. We found that in MAP infected macrophages, TNF-alpha gene expression was
      substantially lower than in macrophages infected with nonpathogenic MS or
      stimulated with LPS. TNF-alpha transcriptional one could not fully explain the
      differential TNF-alpha mRNA expression, suggesting that there must be a
      substantial contribution by post-transcriptional mechanisms.Accordingly, we found
      reduced TNF-alpha mRNA stability in MAP-infected macrophages. Further comparison
      of MAP- and MS-infected macrophages revealed that lower TNF-alpha mRNA stability
      combined with lower mRNA and protein expression in MAP-infected macrophages
      correlated with lower p38 MAPK phosphorylation. These findings were independent
      of viability of MAP and MS. We demonstrate that the major mycobacterial cell-wall
      lipoglycan LM of MAP and MS induced TNF-alpha mRNA transcription,but only the MS
      LM induced p38 MAPK-dependent transcript stabilization. Overall, our data suggest
      that pathogenic mycobacteria cause weak p38 and TNF-alpha mRNA stabilization as a
      result of their structural cell-wall components such as LM and thereby, restrict
      TNF-alpha expression in macrophages.

PMID- 19850886
TI  - Similarities between forms of sheep scrapie and Creutzfeldt-Jakob disease are
      encoded by distinct prion types.
AB  - Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt
      Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are
      characterized by the accumulation of a misfolded protein: the pathological prion
      protein. Ever since bovine sporadic encephalopathy was discovered as the likely
      cause of the new variant of CJD in humans, parallels between human and animal
      transmissible spongiform encephalopathies must be viewed under the aspect of a
      disease risk for humans. In our study we have compared prion characteristics of
      different forms of sheep scrapie with those of different phenotypes of sporadic
      CJD. The disease characteristics of sporadic CJD depend considerably on the prion
      type 1 or 2. Our results show that there are obvious parallels between sporadic
      CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to
      the deposition form of pathological prion protein in the brain, detected by the
      paraffin-embedded-tissue blot and the prion aggregate stability with regard to
      denaturation by the chaotropic salt guanidine hydrochloride. The same applies to
      sporadic CJD type 2 and classical scrapie. The observed parallels between types
      of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of
      prion disease exist in different species. This should be taken into consideration
      when discussing interspecies transmission.

PMID- 19850885
TI  - Identification of EpCAM as a molecular target of prostate cancer stroma.
AB  - To delineate the molecular changes that occur in the tumor microenvironment, we
      previously performed global transcript analysis of human prostate cancer
      specimens using tissue microdissection and expression microarrays. Epithelial and
      stromal compartments were individually studied in both tumor and normal fields.
      Tumor-associated stroma showed a distinctly different expression pattern compared
      with normal stroma, having 44 differentially expressed transcripts, the majority
      of which were up-regulated. In the present study, one of the up-regulated
      transcripts, epithelial cell adhesion activating molecule, was further evaluated
      at the protein level in 20 prostate cancer cases using immunohistochemistry and a
      histomathematical analysis strategy. The epithelial cell adhesion activating
      molecule showed a 76-fold expression increase in the tumor-associated stroma, as
      compared with matched normal stroma. Moreover, Gleason 4 or 5 tumor stroma was
      increased 170-fold relative to matched normal stroma, whereas the Gleason 3 tumor
      area showed only a 36-fold increase, indicating a positive correlation with
      Gleason tumor grade. Since the stromal compartment may be particularly accessible
      to vascular-delivered agents, epithelial cell adhesion activating molecule could
      become a valuable molecular target for imaging or treatment of prostate cancer.

PMID- 19850887
TI  - Hyperoxia-induced lung injury in gamma-glutamyl transferase deficiency is
      associated with alterations in nitrosative and nitrative stress.
AB  - gamma-Glutamyl transferase (GGT) regulates glutathione metabolism and cysteine
      supply. GGT inactivation in GGT(enu1) mice limits cysteine availability causing
      cellular glutathione deficiency. In lung, the resultant oxidant burden is
      associated with increased nitric oxide (NO) production, yet GGT(enu1) mice still
      exhibit higher mortality in hyperoxia. We hypothesized that NO metabolism is
      altered under severe oxidant stress and contributes to lung cellular injury and
      death. We compared lung injury, NO synthase (NOS) expression, nitrate/nitrite
      production, nitroso product formation, peroxynitrite accumulation, and cell death
      in wild-type and GGT(enu1) mice in normoxia and hyperoxia. The role of NOS
      activity in cell death was determined by NOS inhibition. Exposure of wild-type
      mice to hyperoxia caused increased lung injury, altered NO metabolism, and
      induction of cell death compared with normoxia, which was attenuated by NOS
      inhibition. Each of these lung injury indices were magnified in hyperoxia-exposed
      GGT(enu1) mice except nitrosation, which showed a diminished decrease compared
      with wild-type mice. NOS inhibition attenuated cell death only slightly, likely
      due to further exacerbation of oxidant stress. Taken together, these data suggest
      that apoptosis in hyperoxia is partially NO-dependent and reiterate the
      importance of cellular glutathione in lung antioxidant defense. Therefore,
      reduced denitrosylation of proteins, possibly resulting in impaired cellular
      repair, and excessive apoptotic cell death likely contribute to increased lung
      injury and mortality of GGT(enu1) mice in hyperoxia.

PMID- 19850888
TI  - Selective and specific macrophage ablation is detrimental to wound healing in
      mice.
AB  - Macrophages are thought to play important roles during wound healing, but
      definition of these roles has been hampered by our technical inability to
      specifically eliminate macrophages during wound repair. The purpose of this study
      was to test the hypothesis that specific depletion of macrophages after
      excisional skin wounding would detrimentally affect healing by reducing the
      production of growth factors important in the repair process. We used transgenic
      mice that express the human diphtheria toxin (DT) receptor under the control of
      the CD11b promoter (DTR mice) to specifically ablate macrophages during wound
      healing. Mice without the transgene are relatively insensitive to DT, and
      administration of DT to wild-type mice does not alter macrophage or other
      inflammatory cell accumulation after injury and does not influence wound healing.
      In contrast, treatment of DTR mice with DT prevented macrophage accumulation in
      healing wounds but did not affect the accumulation of neutrophils or monocytes.
      Such macrophage depletion resulted in delayed re-epithelialization, reduced
      collagen deposition, impaired angiogenesis, and decreased cell proliferation in
      the healing wounds. These adverse changes were associated with increased levels
      of tumor necrosis factor-alpha and reduced levels of transforming growth factor
      beta1 and vascular endothelial growth factor in the wound. In summary,
      macrophages seem to promote both wound closure and dermal healing, in part by
      regulating the cytokine environment of the healing wound.

PMID- 19850889
TI  - Viral RNA induces type I interferon-dependent cytokine release and cell death in
      mesangial cells via melanoma-differentiation-associated gene-5: Implications for
      viral infection-associated glomerulonephritis.
AB  - Viral RNA can trigger interferon signaling in dendritic cells via the innate
      recognition receptors melanoma-differentiation-associated gene (MDA)-5 and
      retinod-inducible gene (RIG)-I in the cytosol or via Toll-like receptors (TLRs)
      in intracellular endosomes. We hypothesized that viral RNA would also activate
      glomerular mesangial cells to produce type I interferon (IFN) via TLR-dependent
      and TLR-independent pathways. To test this hypothesis, we examined
      Toll/Interleukin-1 receptor domain-containing adaptor-inducing interferon-beta
      (TRIF)-deficient mice, which lack a key adaptor for TLR3 signaling. In primary
      mesangial cells, poly I:C RNA-mediated IFN-beta induction was partially TRIF
      dependent; however, when poly I:C RNA was complexed with cationic lipids to
      enhance cytosolic uptake, mesangial cells produced large amounts of IFN-alpha and
      IFN-beta independent of TRIF. Mesangial cells expressed RIG-I and MDA-5 and their
      mitochondrial adaptor IFN-beta promoter stimulator-1 as well, and small
      interfering RNA studies revealed that MDA5 but not RIG-I was required for
      cytosolic poly I:C RNA signaling. In addition, mesangial cells produced Il-6 on
      stimulation with IFN-alpha and IFN-beta, suggesting an autocrine proinflammatory
      effect. Indeed, blockade of IFN-alphabeta or lack of the IFNA receptor reduced
      viral RNA-induced Il-6 production and apoptotic cell death in mesangial cells.
      Furthermore, viral RNA/cationic lipid complexes increased focal necrosis in
      murine nephrotoxic serum nephritis in association with increased renal mRNA
      expression of IFN-related genes. Thus, TLR-independent recognition of viral RNA
      is a potent inducer of type I interferon in mesangial cells, which can be an
      important mediator of virally induced glomerulonephritis.

PMID- 19850890
TI  - Unique lipids from a common human bacterium represent a new class of Toll-like
      receptor 2 ligands capable of enhancing autoimmunity.
AB  - Recent reports suggest that commensal bacteria may play a down-regulatory role in
      autoimmune disease. In the present studies, we demonstrate that phosphorylated
      dihydroceramides, uniquely structured lipids derived from the common human oral
      bacterium Porphyromonas gingivalis and from bacteria commonly found in the
      gastrointestinal tract and other organs, are capable of enhancing autoimmunity.
      We have previously reported that these lipids have proinflammatory effects on
      human fibroblasts in vitro and, in preliminary studies, have recovered these
      lipids from surgically removed human carotid atheroma, suggesting that they may
      play a role in human inflammatory disease. To investigate whether these lipids
      have functional effects on autoimmunity, we administered phosphorylated
      dihydroceramides to mice with the murine model of multiple sclerosis,
      experimental allergic encephalomyelitis (EAE). We find that these lipids, and
      particularly the phosphoethanolamine dihydroceramide (PE DHC) fraction,
      significantly enhanced EAE. Mechanistically, PE DHC enhances EAE in mice lacking
      natural killer T cells, fails to enhance EAE in Toll-like receptor 2 (TLR2)
      deficient mice and, in vitro, induces dendritic cell interleukin-6 secretion in a
      TLR2-dependent manner. Finally, PE DHC-treated mice with EAE demonstrate a
      decreased percentage of spinal cord Foxp3+ T cells, suggesting that these lipids
      may affect regulatory aspects of adaptive immune responses. Overall, our results
      suggest that phosphorylated dihydroceramides derived from common human bacteria
      function as TLR2 ligands and may play a previously unrecognized role in human
      autoimmune diseases.

PMID- 19850891
TI  - Neuroprotective effect of oligodendrocyte precursor cell transplantation in a
      long-term model of periventricular leukomalacia.
AB  - Perinatal white matter injury, or periventricular leukomalacia (PVL), is the most
      common cause of brain injury in premature infants and is the leading cause of
      cerebral palsy. Despite increasing numbers of surviving extreme premature infants
      and associated long-term neurological morbidity, our understanding and treatment
      of PVL remains incomplete. Inflammation- or ischemia/hypoxia-based rodent models,
      although immensely valuable, are largely restricted to reproducing short-term
      features of up to 3 weeks after injury. Given the long-term sequelae of PVL,
      there is a need for subchronic models that will enable testing of putative
      neuroprotective therapies. Here, we report long term characterization of a
      neonatal inflammation-induced rat model of PVL. We show bilateral
      ventriculomegaly, inflammation, reactive astrogliosis, injury to pre
      oligodendrocytes, and neuronal loss 8 weeks after injury. We demonstrate
      neuroprotective effects of oligodendrocyte precursor cell transplantation. Our
      findings present a subchronic model of PVL and highlight the tissue protective
      effects of oligodendrocyte precursor cell transplants that demonstrate the
      potential of cell-based therapy for PVL.

PMID- 19850893
TI  - The expression of AIP-related molecules in elucidation of cellular pathways in
      pituitary adenomas.
AB  - Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP)
      gene predispose to the development of pituitary adenomas. Here, we characterized
      AIP mutation positive (AIPmut+) and AIP mutation negative (AIPmut-) pituitary
      adenomas by immunohistochemistry. The expressions of the AIP-related proteins
      aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), cyclin
      dependent kinase inhibitor 1B encoding p27(Kip1), and hypoxia-inducible factor 1
      alpha were examined in 14 AIPmut+ and 53 AIPmut- pituitary adenomas to detect
      possible expression differences. In addition, the expression of CD34, an
      endothelial and hematopoietic stem cell marker, was analyzed. We found ARNT to be
      less frequently expressed in AIPmut+ pituitary adenomas (P = 0.001), suggesting
      that AIP regulates the ARNT levels. AIP small interfering RNA-treated HeLa,
      HEK293, or Aip-null mouse embryonic fibroblast cells did not show lowered
      expression of ARNT. Instead, in the pituitary adenoma cell line GH3, Aip
      silencing caused a partial reduction of Arnt and a clear increase in cell
      proliferation. We also observed a trend for increased expression of nuclear AHR
      in AIPmut+ samples, although the difference was not statistically significant (P
      = 0.06). The expressions of p27(Kip1), hypoxia-inducible factor 1-alpha, or CD34
      did not differ between tumor types. The present study shows that the expression
      of ARNT protein is significantly reduced in AIPmut+ tumors. We suggest that the
      down-regulation of ARNT may be connected to an imbalance in AHR/ARNT complex
      formation arising from aberrant cAMP signaling.

PMID- 19850894
TI  - Doppler embolic signals in cerebrovascular disease and prediction of stroke risk:
      a systematic review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Asymptomatic embolic signals (ES) detected using
      transcranial Doppler have been reported in patients with potential cerebral
      embolic sources. They may be useful in risk stratification and in assessing
      therapies. First, it is essential to show whether they predict stroke risk.
      METHODS: A systematic review and meta-analysis was performed to determine the
      prognostic value of ES in different potential cerebral embolic sources. Studies
      were identified that used transcranial Doppler to detect ES and included
      prospective stroke/TIA follow-up. Numbers of ES-positive and ES-negative patients
      were extracted with stroke/TIA and stroke alone outcomes. RESULTS: ES are most
      frequent in large artery disease, less frequent in cardioembolic stroke, and
      infrequent in lacunar stroke. Data relating ES to future stroke risk were
      available for acute stroke, large artery disease, and the perioperative period of
      carotid endarterectomy. For symptomatic carotid stenosis, ES predicted stroke
      alone (OR, 9.57; 95%CI, 1.54 to 59.38; P=0.02) and stroke/TIA (OR, 6.36; 95% CI,
      2.90-13.96; P<0.00001). For asymptomatic carotid stenosis, ES predicted stroke
      alone (OR, 7.46; 95% CI, 2.24-24.89; P=0.001) and stroke/TIA (OR, 12.00; 95% CI,
      2.43-59.34; P=0.002) but with heterogeneity (P=0.004). In acute stroke ES
      predicted stroke alone (OR, 2.44; 95% CI, 1.17-5.08; P=0.02) and stroke/TIA (OR,
      3.71; 95% CI, 1.64-8.38; P=0.002). A high frequency of ES immediately after
      carotid endarterectomy predicted stroke alone (OR, 24.54; 95% CI, 7.88-76.43;
      P<0.00001) and stroke/TIA (OR, 32.04; 95% CI, 11.36-90.39; P<0.00001).
      CONCLUSIONS: ES predict stroke risk in acute stroke, symptomatic carotid
      stenosis, and postoperatively after carotid endarterectomy; in asymptomatic
      carotid stenosis, data are less robust. In these conditions ES may be useful in
      risk stratification and in assessing therapeutic efficacy. For other embolic
      sources, further prospective data are required.

PMID- 19850892
TI  - Suppression of PLCbeta2 by endotoxin plays a role in the adenosine A(2A) receptor
      mediated switch of macrophages from an inflammatory to an angiogenic phenotype.
AB  - Toll-like receptor (TLR) 2, 4, 7, and 9 agonists, together with adenosine A(2A)
      receptor (A(2A)R) agonists, switch macrophages from an inflammatory (M1) to an
      angiogenic (M2-like) phenotype. This switch involves induction of A(2A)Rs by TLR
      agonists, down-regulation of tumor necrosis factor alpha (TNFalpha) and
      interleukin-12, and up-regulation of vascular endothelial growth factor (VEGF)
      and interleukin-10 expression. We show here that the TLR4 agonist
      lipopolysaccharide (LPS) induces rapid and specific post-transcriptional down
      regulation of phospholipase C(PLC)beta1 and beta2 expression in macrophages by de
      stabilizing their mRNAs. The PLCbeta inhibitor U73122 down-regulates TNFalpha
      expression by macrophages, and in the presence of A(2A)R agonists, up-regulates
      VEGF, mimicking the synergistic action of LPS with A(2A)R agonists. Selective
      down-regulation of PLCbeta2, but not PLCbeta1, using small-interfering RNA
      resulted in increased VEGF expression in response to A(2A)R agonists, but did not
      suppress TNFalpha expression. Macrophages from PLCbeta2(-/-) mice also expressed
      increased VEGF in response to A(2A)R agonists. LPS-mediated suppression of
      PLCbeta1 and beta2 is MyD88-dependent. In a model of endotoxic shock, LPS (35
      microg/mouse, i.p.) suppressed PLCbeta1 and beta2 expression in spleen, liver,
      and lung of wild-type but not MyD88(-/-) mice. These studies indicate that LPS
      suppresses PLCbeta1 and beta2 expression in macrophages in vitro and in several
      tissues in vivo. These results suggest that suppression of PLCbeta2 plays an
      important role in switching M1 macrophages into an M2-like state.

PMID- 19850896
TI  - Fragmentation of the classical magnetic resonance mismatch "penumbral" pattern
      with time.
AB  - BACKGROUND AND PURPOSE: The classical mismatch pattern in the middle cerebral
      artery territory stroke on MR is defined by a central diffusion-weighted image
      core with surrounding mismatch tissue. Because of variable rates of tissue
      salvage, we hypothesized that this pattern may fragment over time and may be
      influenced by vessel patency, mismatch volume, and infarct core location.
      METHODS: Patients were recruited with MR studies performed within 48 hours of
      ischemic stroke. Mismatch patterns based on diffusion-weighted/perfusion-weighted
      images were categorized as classical (majority of the diffusion-weighted image
      within the perfusion-weighted image lesion) or nonclassical (fragmented)
      patterns. The proportion of patterns was assessed with reference to time, vessel
      patency, mismatch volume, and infarct core location. RESULTS: Sixty-seven
      patients (33 classical [49.3%] and 34 nonclassical patterns [50.7%]) were studied
      within 48 hours (median age, 74.0 years). Compared to the nonclassical pattern,
      the classical pattern had a shorter time to MR (3.4 hours vs 10.4 hours; P=0.004)
      and a larger mismatch volume (62.0 mL vs 3.5 mL; P<0.0001). The positive
      predictors for the classical pattern were earlier time, vessel occlusion,
      superficial core location, and larger mismatch volume. CONCLUSIONS: The classical
      mismatch pattern may fragment with time. Over 48 hours the classical pattern is
      seen earlier after stroke onset, with higher rates of vessel occlusion and larger
      mismatch volumes.

PMID- 19850897
TI  - Neuroimaging demonstration of evolving small vessel ischemic injury in cerebral
      amyloid angiopathy.
AB  - BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy is a small to medium
      vasculopathy most commonly associated with symptomatic intracerebral hemorrhage
      and microbleeds. Summary of Case- We present a patient with cerebral microbleeds
      and likely amyloid angiopathy with evolving ischemic lesions visualized on
      diffusion-weighted imaging. CONCLUSIONS: This case captures with serial MRI the
      evolving and dynamic nature of cerebral amyloid angiopathy and particularly
      illustrates the subclinical, yet progressive, ischemic aspects of this
      vasculopathic process.

PMID- 19850898
TI  - Higher systolic blood pressure is associated with increased water diffusivity in
      normal-appearing white matter.
AB  - BACKGROUND AND PURPOSE: Hypertension is associated with the development of white
      matter lesions in older people. Diffusion tensor MRI can detect subtle,
      previsible white matter damage, but relationships between diffusion tensor MRI
      parameters and blood pressure (BP) remain unclear. We examined correlations among
      mean diffusivity (MD), fractional anisotropy and BP in 45 men aged 71 to 76
      years. METHODS: MD and fractional anisotropy were measured in 6 regions of
      interest in normal-appearing white matter. Visible white matter lesions were
      quantified using the Fazekas scale. Both were correlated with systolic and
      diastolic BP. RESULTS: Systolic BP was positively and significantly correlated
      with MD in all 6 regions (r=0.31 to 0.45; P=0.037 to 0.002). MD was also
      correlated with diastolic BP in the genu of the corpus callosum (r=0.34,
      P=0.018). A summary factor derived from principal component analysis of the MD
      measurements accounted for 53.8% of the variance and correlated at r=0.51
      (P<0.001) with systolic BP and r=0.33 (P=0.028) with diastolic BP. Fractional
      anisotropy did not correlate significantly with BP. Deep white matter Fazekas
      scores correlated with diastolic BP (rho=0.35, P=0.019). CONCLUSIONS: The
      increase in MD without change in fractional anisotropy indicates that, in normal
      appearing white matter, higher BP may be associated with increased extracellular
      fluid before any cytoarchitectural damage occurs.

PMID- 19850895
TI  - Patient dissatisfaction with acute stroke care.
AB  - BACKGROUND AND PURPOSE: Riks-Stroke, the Swedish Stroke Register, was used to
      explore patient characteristics and stroke services as determinants of patient
      dissatisfaction with acute in-hospital care. METHODS: All 79 hospitals in Sweden
      admitting acute stroke patients participate in Riks-Stroke. During 2001 to 2007,
      104,876 patients (87% of survivors) responded to a follow-up questionnaire 3
      months after acute stroke; this included questions on satisfaction with various
      aspects of stroke care. RESULTS: The majority (>90%) were satisfied with acute in
      hospital stroke care. Dissatisfaction was closely associated with outcome at 3
      months. Patient who were dependent regarding activities of daily living, felt
      depressed, or had poor self-perceived general health were more likely to be
      dissatisfied. Dissatisfaction with global acute stroke care was linked to
      dissatisfaction with other aspects of care, including rehabilitation and support
      by community services. Patients treated in stroke units were less often
      dissatisfied than patients in general wards, as were patients who had been
      treated in a small hospital (vs medium or large hospitals) and patient who had
      participated in discharge planning. In multivariate analyses, the strongest
      predictor of dissatisfaction with acute care was poor outcome (dependency
      regarding activities of daily living, depressed mood, poor self-perceived
      health). CONCLUSIONS: Dissatisfaction with in-hospital acute stroke care is part
      of a more extensive complex comprising poor functional outcome, depressive mood,
      poor self-perceived general health, and dissatisfaction not only with acute care
      but also with health care and social services at large. Several aspects of stroke
      care organization are associated with a lower risk of dissatisfaction.

PMID- 19850899
TI  - Megakaryocyte-erythroid lineage promiscuity in EKLF null mouse blood.
AB  - Commitment towards megakaryocyte versus erythroid blood cell lineages occurs in
      the megakaryocyte-erythroid progenitor, where mutually exclusive expression of
      either EKLF (Klf1) or Fli1 defines alternative outcomes. Here we show there is a
      marked increase in the number of circulating platelets in mice lacking the
      erythroid transcription factor EKLF. In addition, committed erythroid cells
      retain key signatures of megakaryocytes both on the cell surface and at the mRNA
      level. We also show that the effect of EKLF on megakaryocyte-erythroid progenitor
      lineage decision and commitment is cell autonomous in bone marrow reconstitution
      assays where stem cells lacking EKLF favor the megakaryocyte differentiation
      pathway. We conclude the megakaryocyte program is aberrantly activated in EKLF
      null erythroid cells.

PMID- 19850900
TI  - Development of an ELISA strip for the detection of alpha thalassemias.

PMID- 19850902
TI  - Decitabine versus 5-azacitidine for the treatment of myelodysplastic syndrome:
      adjusted indirect meta-analysis.

PMID- 19850901
TI  - Sperm quality before treatment in patients with early stage Hodgkin's lymphoma
      enrolled in EORTC-GELA Lymphoma Group trials.
AB  - BACKGROUND: Although widely recommended, cryopreservation of sperm is sometimes
      not performed for patients with Hodgkin's lymphoma because of presumed poor sperm
      quality related to the disease. We investigated sperm quality and factors
      determining it in untreated patients with early stage Hodgkin's lymphoma. DESIGN
      AND METHODS: Of 2362 males who participated in EORTC H6-H9 trials, 474 (20%) had
      data available. Sperm quality was defined according to World Health Organization
      guidelines. Determining factors were studied by logistic regression analysis.
      RESULTS: The median sperm concentration was 40x10(6)/mL (range, 0-345x10(6)/mL)
      and the median motility 50% (range, 0-90%). Sperm quality was good (concentration
      >or=20x10(6)/mL and motility >or=50%), intermediate (concentration
      >or=5x10(6)/mL) and poor (concentration <5x10(6)/mL but >0) in 41%, 49% and 7% of
      patients, respectively. Three percent of the patients were azoospermic. No
      relation was found between sperm quality and age or clinical stage of the
      Hodgkin's lymphoma, but B-symptoms and elevated erythrocyte sedimentation rate
      predicted poor sperm quality. The odds ratios for the association of poor sperm
      quality with the variables examined were: presence of B-symptoms, 2.77 (95% CI,
      1.50-5.12; p=0.001); erythrocyte sedimentation rate of 50 mm/h or greater, 2.35
      (95% CI, 1.24-4.43; p=0.009); fever, 3.22 (95% CI, 1.41-7.33; p=0.005), and night
      sweats, 3.78 (95% CI, 1.97-7.26; p<0.001). There was no relation between sperm
      quality and pre-treatment follicle stimulating hormone level. CONCLUSIONS: In
      this large study of males with Hodgkin's lymphoma, 90% had good or intermediate
      sperm quality. Three percent were azoospermic. There was an association between
      sperm quality and the presence or absence of B-symptoms, in particular fever and
      night sweats. With modern fertilization techniques, in most patients with early
      stage Hodgkin's lymphoma sperm quality before treatment is good enough for future
      fatherhood.

PMID- 19850903
TI  - Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008
      registry study.
AB  - BACKGROUND: The aim of this study was to evaluate prognostic factors, treatments
      and outcome of invasive aspergillosis in patients with acute myeloid leukemia
      based on data collected in a registry. DESIGN AND METHODS: The registry, which
      was activated in 2004 and closed in 2007, collected data on patients with acute
      myeloid leukemia, admitted to 21 hematologic divisions in tertiary care centers
      or university hospitals in Italy, who developed proven or probable invasive
      aspergillosis. RESULTS: One hundred and forty cases of invasive aspergillosis
      were collected, with most cases occurring during the period of post-induction
      aplasia, the highest risk phase in acute myeloid leukemia. The mortality rate
      attributable to invasive aspergillosis was 27%, confirming previous reports of a
      downward trend in this rate. Univariate and multivariate analyses revealed that
      the stage of acute myeloid leukemia and the duration of, and recovery from,
      neutropenia were independent prognostic factors. We analyzed outcomes after
      treatment with the three most frequently used drugs (liposomal amphotericin B,
      caspofungin, voriconazole). No differences emerged in survival at day 120 or in
      the overall response rate which was 71%, ranging from 61% with caspofungin to 84%
      with voriconazole. CONCLUSIONS: Our series confirms the downward trend in
      mortality rates reported in previous series, with all new drugs providing similar
      survival and response rates. Recovery from neutropenia and disease stage are
      crucial prognostic factors. Efficacious antifungal drugs bridge the period of
      maximum risk due to poor hematologic and immunological reconstitution.

PMID- 19850904
TI  - Discrete contributions of elastic fiber components to arterial development and
      mechanical compliance.
AB  - OBJECTIVE: Even though elastin and fibrillin-1 are the major structural
      components of elastic fibers, mutations in elastin and fibrillin-1 lead to
      narrowing of large arteries in supravalvular aortic stenosis and dilation of the
      ascending aorta in Marfan syndrome, respectively. A genetic approach was
      therefore used here to distinguish the differential contributions of elastin and
      fibrillin-1 to arterial development and compliance. METHODS AND RESULTS: Key
      parameters of cardiovascular function were compared among adult mice
      haploinsufficient for elastin (Eln(+/-)), fibrillin-1 (Fbn1(+/-)), or both
      proteins (dHet). Physiological and morphological comparisons correlate elastin
      haploinsufficiency with increased blood pressure and vessel length and tortuosity
      in dHet mice, and fibrillin-1 haploinsufficiency with increased aortic diameter
      in the same mutant animals. Mechanical tests confirm that elastin and fibrillin-1
      impart elastic recoil and tensile strength to the aortic wall, respectively.
      Additional ex vivo analyses demonstrate additive and overlapping contributions of
      elastin and fibrillin-1 to the material properties of vascular tissues. Lastly,
      light and electron microscopy evidence implicates fibrillin-1 in the hypertension
      promoted remodeling of the elastin-deficient aorta. CONCLUSIONS: These results
      demonstrate that elastin and fibrillin-1 have both differential and complementary
      roles in arterial wall formation and function, and advance our knowledge of the
      structural determinants of vascular physiology and disease.

PMID- 19850905
TI  - Heritability of thromboxane A2 and prostaglandin E2 biosynthetic machinery in a
      Spanish population.
AB  - OBJECTIVE: Prostanoids play a critical role in clinical areas such as
      inflammation, thrombosis, immune response, and cancer. Although some studies
      suggest that there are genes that determine variability of some prostanoid
      related phenotypes, the genetic influence on these traits has not been evaluated.
      METHODS AND RESULTS: The relative contributions of genetic and environmental
      influences to the prostanoid biosynthetic pathway-related phenotypes,
      cyclooxygenase isoenzymes, microsomal-PGE-synthase-1 and TxA-synthase expression,
      and thromboxane-A(2) and prostaglandin-E(2) production by stimulated whole blood,
      were assessed in a sample of 308 individuals in 15 extended families. The effects
      of measured covariates (such as sex, age, and smoking), genes, and environmental
      variables shared by members of a household were quantified. Heritabilities
      ranging from 0.406 to 0.634 for enzyme expression and from 0.283 to 0. 751 for
      prostanoid production were found. CONCLUSIONS: These results demonstrate clearly
      the importance of genetic factors in determining variation in phenotypes that are
      components of the prostanoid biosynthetic pathways. The presence of such strong
      genetic effects suggest that it will be possible to localize previously unknown
      genes that influence quantitative variation in these phenotypes, some of which
      affect multiple aspects of cell biology, with important clinical implications.

PMID- 19850906
TI  - Filtering of deep sequencing data reveals the existence of abundant Dicer
      dependent small RNAs derived from tRNAs.
AB  - Deep sequencing technologies such as Illumina, SOLiD, and 454 platforms have
      become very powerful tools in discovering and quantifying small RNAs in diverse
      organisms. Sequencing small RNA fractions always identifies RNAs derived from
      abundant RNA species such as rRNAs, tRNAs, snRNA, and snoRNA, and they are widely
      considered to be random degradation products. We carried out bioinformatic
      analysis of deep sequenced HeLa RNA and after quality filtering, identified
      highly abundant small RNA fragments, derived from mature tRNAs that are likely
      produced by specific processing rather than from random degradation. Moreover, we
      showed that the processing of small RNAs derived from tRNA(Gln) is dependent on
      Dicer in vivo and that Dicer cleaves the tRNA in vitro.

PMID- 19850907
TI  - Improved RNA preservation for immunolabeling and laser microdissection.
AB  - Microdissection techniques have the potential to allow for transcriptome analyses
      in specific populations of cells that are isolated from heterogeneous tissues
      such as the nervous system and certain cancers. Problematically, RNA is not
      stable under the labeling conditions usually needed to identify the cells of
      interest for microdissection. We have developed an immunolabeling method that
      utilizes a high salt buffer to stabilize RNA during prolonged antibody
      incubations. We first assessed RNA integrity by three methods and found that
      tissue incubated in high salt buffer for at least 20 h yielded RNA of similar
      quality to that for RNA extracted from fresh-frozen tissue, which is considered
      highest quality. Notably, the integrity was superior to that for RNA extracted
      from tissue processed using rapid immunolabeling procedures (5 min total
      duration). We next established that high salt buffer was compatible with
      immunolabeling, as demonstrated by immunofluorescent detection of dopamine
      neurons in the brain. Finally, we laser microdissected dopamine neurons that were
      immunolabeled using high salt buffer and demonstrated that RNA integrity was
      preserved. Our described method yields high quality RNA from immunolabeled
      microdissected cells, an essential requirement for meaningful genomics
      investigations of normal and pathological cells isolated from complex tissues.

PMID- 19850908
TI  - CpG-island promoters drive transcription of human telomeres.
AB  - The longstanding dogma that telomeres, the heterochromatic extremities of linear
      eukaryotic chromosomes, are transcriptionally silent was overturned by the
      discovery that DNA-dependent RNA polymerase II (RNAPII) transcribes telomeric DNA
      into telomeric repeat-containing RNA (TERRA). Here, we show that CpG dinucleotide
      rich DNA islands, shared among multiple human chromosome ends, promote
      transcription of TERRA molecules. TERRA promoters sustain cellular expression of
      reporter genes, are located immediately upstream of TERRA transcription start
      sites, and are bound by active RNAPII in vivo. Finally, the identified promoter
      CpG dinucleotides are methylated in vivo, and cytosine methylation negatively
      regulates TERRA abundance. The existence of subtelomeric promoters, driving TERRA
      transcription from independent chromosome ends, supports the idea that TERRA
      exerts fundamental functions in the context of telomere biology.

PMID- 19850909
TI  - Splicing of mRNA mediated by tRNA sequences in mouse cells.
AB  - tRNA splicing is essential for the formation of tRNAs and therefore for gene
      expression. A circularly permuted sequence of an amber-suppressor pre-tRNA gene
      was inserted into the sequence encoding the mouse NEMO protein. We demonstrated
      that, in mouse cells, the hybrid pre-tRNA/pre-mRNAs can be spliced precisely at
      the sites of the pre-tRNA intron. This splicing reaction produces functional
      tRNAs that suppress amber codons as well as translatable mRNAs that sustain the
      NF-kappaB activation pathway. The RNA molecules extracted from mouse cells were
      amplified by RT-PCR, and their sequences were determined, confirming the identity
      of the splice junctions. We then applied the Archaea-express technology, in which
      an archaeal RNA endonuclease is expressed in mouse cells. We show that both the
      endogenous eukaryal endonuclease and the archaeal one cleave the hybrid pre
      tRNA/pre-mRNAs in the same manner with an additive effect.

PMID- 19850910
TI  - Sliced microRNA targets and precise loop-first processing of MIR319 hairpins
      revealed by analysis of the Physcomitrella patens degradome.
AB  - Expression profiling of the 5' ends of uncapped mRNAs ("degradome" sequencing)
      can be used to empirically catalog microRNA (miRNA) targets, to probe patterns of
      miRNA hairpin processing, to examine mRNA decay, and to analyze accumulation of
      endogenous short interfering RNA (siRNA) precursors. We sequenced and analyzed
      the degradome of the moss Physcomitrella patens, an important model system for
      functional genomic analyses in plant evolution. A total of 52 target mRNAs of 27
      different Physcomitrella miRNA families were identified. Many targets of both
      more conserved and less conserved miRNA families encoded putative regulatory
      proteins. Remnants of MIRNA hairpin processing also populated the degradome data
      and indicated an unusual "loop-first" mode of precise processing for the MIR319
      gene family. Precise loop-first processing was confirmed for native
      Physcomitrella, rice, and Arabidopsis MIR319 hairpins, as well as an Arabidopsis
      artificial MIRNA (aMIRNA) based upon a MIR319 backbone. MIR319 is thus a
      conserved exception to the general rule of loop-last processing of MIRNA
      hairpins. Loop-first MIR319 processing may contribute to the high efficacy of a
      widely used MIR319-based strategy for aMIRNA production in plants.

PMID- 19850911
TI  - The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two
      step reaction to form the RNA cap structure.
AB  - The 5'-end of the flavivirus genome harbors a methylated (m7)GpppA(2'OMe) cap
      structure, which is generated by the virus-encoded RNA triphosphatase, RNA
      (guanine-N7) methyltransferase, nucleoside 2'-O-methyltransferase, and RNA
      guanylyltransferase. The presence of the flavivirus guanylyltransferase activity
      in NS5 has been suggested by several groups but has not been empirically proven.
      Here we provide evidence that the N-terminus of the flavivirus NS5 protein is a
      true RNA guanylyltransferase. We demonstrate that GTP can be used as a substrate
      by the enzyme to form a covalent GMP-enzyme intermediate via a phosphoamide bond.
      Mutational studies also confirm the importance of a specific lysine residue in
      the GTP binding site for the enzymatic activity. We show that the GMP moiety can
      be transferred to the diphosphate end of an RNA transcript harboring an adenosine
      as the initiating residue. We also demonstrate that the flavivirus RNA
      triphosphatase (NS3 protein) stimulates the RNA guanylyltransferase activity of
      the NS5 protein. Finally, we show that both enzymes are sufficient and necessary
      to catalyze the de novo formation of a methylated RNA cap structure in vitro
      using a triphosphorylated RNA transcript. Our study provides biochemical evidence
      that flaviviruses encode a complete RNA capping machinery.

PMID- 19850912
TI  - Nonsense-mediated mRNA decay mutes the splicing defects of spliceosome component
      mutations.
AB  - The role of many splicing factors in pre-mRNA splicing and the involvement of
      these factors in the processing of specific transcripts have often been defined
      through the analysis of loss-of-function mutants in vivo. Here we show that
      inactivating the nonsense-mediated mRNA decay (NMD) results in an enhancement of
      splicing phenotypes associated with several S. cerevisiae splicing factor
      mutations. Tiling microarrays showed that inactivation of the NMD factor Upf1p in
      the prp17Delta and prp18Delta mutant strains results in a larger spectrum of
      splicing defects than what is observed in the single mutants, including new
      transcripts previously shown unaffected by Prp17p or Prp18p inactivation.
      Inactivation of Upf1p in the second step/recycling factor prp22-1 mutant and in
      the nam8Delta and mud1Delta U1 snRNP component mutants also increase unspliced
      precursor accumulation of several specific transcripts. In addition, deletion of
      UPF1 partially suppresses the growth defects associated with the prp17Delta or
      prp22-1 mutations, demonstrating a positive genetic interaction between NMD and
      splicing factor mutants. These results show that RNA surveillance by NMD can mask
      some of the effects of splicing factor mutations, and that the roles of splicing
      factors cannot be fully understood in vivo unless RNA degradation systems that
      degrade unspliced precursors are also inactivated.

PMID- 19850914
TI  - Do conformational biases of simple helical junctions influence RNA folding
      stability and specificity?
AB  - Structured RNAs must fold into their native structures and discriminate against a
      large number of alternative ones, an especially difficult task given the limited
      information content of RNA's nucleotide alphabet. The simplest motifs within
      structured RNAs are two helices joined by nonhelical junctions. To uncover the
      fundamental behavior of these motifs and to elucidate the underlying physical
      forces and challenges faced by structured RNAs, we computationally and
      experimentally studied a tethered duplex model system composed of two helices
      joined by flexible single- or double-stranded polyethylene glycol tethers, whose
      lengths correspond to those typically observed in junctions from structured RNAs.
      To dissect the thermodynamic properties of these simple motifs, we
      computationally probed how junction topology, electrostatics, and tertiary
      contact location influenced folding stability. Small-angle X-ray scattering was
      used to assess our predictions. Single- or double-stranded junctions, independent
      of sequence, greatly reduce the space of allowed helical conformations and
      influencing the preferred location and orientation of their adjoining helices. A
      double-stranded junction guides the helices along a hinge-like pathway. In
      contrast, a single-stranded junction samples a broader set of conformations and
      has different preferences than the double-stranded junction. In turn, these
      preferences determine the stability and distinct specificities of tertiary
      structure formation. These sequence-independent effects suggest that properties
      as simple as a junction's topology can generally define the accessible
      conformational space, thereby stabilizing desired structures and assisting in
      discriminating against misfolded structures. Thus, junction topology provides a
      fundamental strategy for transcending the limitations imposed by the low
      information content of RNA primary sequence.

PMID- 19850915
TI  - Bacillus subtilis RNase J1 endonuclease and 5' exonuclease activities in the
      turnover of DeltaermC mRNA.
AB  - RNase J1, a ribonuclease with 5' exonuclease and endonuclease activities, is an
      important factor in Bacillus subtilis mRNA decay. A model for RNase J1
      endonuclease activity in mRNA turnover has RNase J1 binding to the 5' end and
      tracking to a target site downstream, where it makes a decay-initiating cleavage.
      The upstream fragment from this cleavage is degraded by 3' exonucleases; the
      downstream fragment is degraded by RNase J1 5' exonuclease activity. Previously,
      DeltaermC mRNA was used to show 5'-end dependence of mRNA turnover. Here we used
      DeltaermC mRNA to probe RNase J1-dependent degradation, and the results were
      consistent with aspects of the model. DeltaermC mRNA showed increased stability
      in a mutant strain that contained a reduced level of RNase J1. In agreement with
      the tracking concept, insertion of a strong stem-loop structure at +65 resulted
      in increased stability. Weakening this stem-loop structure resulted in reversion
      to wild-type stability. RNA fragments containing the 3' end were detected in a
      strain with reduced RNase J1 expression, but were undetectable in the wild type.
      The 5' ends of these fragments mapped to the upstream side of predicted stem-loop
      structures, consistent with an impediment to RNase J1 5' exonuclease
      processivity. A DeltaermC mRNA deletion analysis suggested that decay-initiating
      endonuclease cleavage could occur at several sites near the 3' end. However, even
      in the absence of these sites, stability was further increased in a strain with
      reduced RNase J1, suggesting alternate pathways for decay that could include
      exonucleolytic decay from the 5' end.

PMID- 19850913
TI  - Powering through ribosome assembly.
AB  - Ribosome assembly is required for cell growth in all organisms. Classic in vitro
      work in bacteria has led to a detailed understanding of the biophysical,
      thermodynamic, and structural basis for the ordered and correct assembly of
      ribosomal proteins on ribosomal RNA. Furthermore, it has enabled reconstitution
      of active subunits from ribosomal RNA and proteins in vitro. Nevertheless, recent
      work has shown that eukaryotic ribosome assembly requires a large macromolecular
      machinery in vivo. Many of these assembly factors such as ATPases, GTPases, and
      kinases hydrolyze nucleotide triphosphates. Because these enzymes are likely
      regulatory proteins, much work to date has focused on understanding their role in
      the assembly process. Here, we review these factors, as well as other sources of
      energy, and their roles in the ribosome assembly process. In addition, we propose
      roles of energy-releasing enzymes in the assembly process, to explain why energy
      is used for a process that occurs largely spontaneously in bacteria. Finally, we
      use literature data to suggest testable models for how these enzymes could be
      used as targets for regulation of ribosome assembly.

PMID- 19850916
TI  - IRAK-1 contributes to lipopolysaccharide-induced reactive oxygen species
      generation in macrophages by inducing NOX-1 transcription and Rac1 activation and
      suppressing the expression of antioxidative enzymes.
AB  - Inflammatory stimulants such as bacterial endotoxin (lipopolysaccharide (LPS))
      are known to induce tissue damage and injury partly through the induction of
      reactive oxygen species (ROS). Although it is recognized that the induction of
      ROS in macrophages by LPS depends upon the expression and activation of NADPH
      oxidase, as well as the suppression of antioxidative enzymes involved in ROS
      clearance, the underlying molecular mechanisms are poorly defined. In this study,
      we examined the contribution of the interleukin-1 receptor-associated kinase 1
      (IRAK-1) to LPS-induced generation of ROS. We observed that LPS induced
      significantly less ROS in IRAK-1(-/-) macrophages, indicating that IRAK-1 is
      critically involved in the induction of ROS. Mechanistically, we observed that
      IRAK-1 is required for LPS-induced expression of NOX-1, a key component of NADPH
      oxidase, via multiple transcription factors, including p65/RelA, C/EBPbeta, and
      C/EBPdelta. On the other hand, we demonstrated that IRAK-1 associated with and
      activated small GTPase Rac1, a known activator of NOX-1 oxidase enzymatic
      activity. IRAK-1 forms a close complex with Rac1 via a novel LWPPPP motif within
      the variable region of IRAK-1. On the other hand, we also observed that IRAK-1 is
      required for LPS-mediated suppression of peroxisome proliferator-activated
      receptor alpha and PGC-1alpha, nuclear factors essential for the expression of
      antioxidative enzymes such as GPX3 and catalase. Consequently, injection of LPS
      causes significantly less plasma lipid peroxidation in IRAK-1(-/-) mice compared
      with wild type mice. Taken together, our study reveals IRAK-1 as a novel
      component involved in the generation of ROS induced by LPS.

PMID- 19850917
TI  - Plumieribetin, a fish lectin homologous to mannose-binding B-type lectins,
      inhibits the collagen-binding alpha1beta1 integrin.
AB  - Recently, a few fish proteins have been described with a high homology to B-type
      lectins of monocotyledonous plants. Because of their mannose binding activity,
      they have been ascribed a role in innate immunity. By screening various fish
      venoms for their integrin inhibitory activity, we isolated a homologous protein
      from the fin stings and skin mucus of the scorpionfish (Scorpaena plumieri). This
      protein inhibits alpha1beta1 integrin binding to basement membrane collagen IV.
      By protein chemical and spectroscopic means, we demonstrated that this fish
      protein, called plumieribetin, is a homotetramer and contains a high content of
      anti-parallel beta strands, similar to the mannose-binding monocot B-lectins. It
      lacks both N-linked glycoconjugates and common O-glycan motifs. Despite its B
      lectin-like structure, plumieribetin binds to alpha1beta1 integrin irrespective
      of N-glycosylation, suggesting a direct protein-protein interaction. This
      interaction is independent of divalent cations. On the cellular level,
      plumieribetin failed to completely detach hepatocarcinoma HepG2 cells and primary
      arterial smooth muscle cells from the collagen IV fragment CB3. However,
      plumieribetin weakened the cell-collagen contacts, reduced cell spreading, and
      altered the actin cytoskeleton, after the compensating alpha2beta1 integrin was
      blocked. The integrin inhibiting effect of plumieribetin adds a new function to
      the B-lectin family, which is known for pathogen defense.

PMID- 19850919
TI  - Modulating effects of the plug, helix, and N- and C-terminal domains on channel
      properties of the PapC usher.
AB  - The chaperone/usher system is one of the best characterized pathways for protein
      secretion and assembly of cell surface appendages in Gram-negative bacteria. In
      particular, this pathway is used for biogenesis of the P pilus, a key virulence
      factor used by uropathogenic Escherichia coli to adhere to the host urinary
      tract. The P pilus individual subunits bound to the periplasmic chaperone PapD
      are delivered to the outer membrane PapC usher, which serves as an assembly
      platform for subunit incorporation into the pilus and secretion of the pilus
      fiber to the cell surface. PapC forms a dimeric, twin pore complex, with each
      monomer composed of a 24-stranded transmembrane beta-barrel channel, an internal
      plug domain that occludes the channel, and globular N- and C-terminal domains
      that are located in the periplasm. Here we have used planar lipid bilayer
      electrophysiology to characterize the pore properties of wild type PapC and
      domain deletion mutants for the first time. The wild type pore is closed most of
      the time but displays frequent short-lived transitions to various open states. In
      comparison, PapC mutants containing deletions of the plug domain, an alpha-helix
      that caps the plug domain, or the N- and C-terminal domains form channels with
      higher open probability but still exhibiting dynamic behavior. Removal of the
      plug domain results in a channel with extremely large conductance. These
      observations suggest that the plug gates the usher channel closed and that the
      periplasmic domains and alpha-helix function to modulate the gating activity of
      the PapC twin pore.

PMID- 19850918
TI  - Aminopyridines potentiate synaptic and neuromuscular transmission by targeting
      the voltage-activated calcium channel beta subunit.
AB  - Aminopyridines such as 4-aminopyridine (4-AP) are widely used as voltage
      activated K(+) (Kv) channel blockers and can improve neuromuscular function in
      patients with spinal cord injury, myasthenia gravis, or multiple sclerosis. Here,
      we present novel evidence that 4-AP and several of its analogs directly stimulate
      high voltage-activated Ca(2+) channels (HVACCs) in acutely dissociated neurons. 4
      AP, 4-(aminomethyl)pyridine, 4-(methylamino)pyridine, and 4
      di(methylamino)pyridine profoundly increased HVACC, but not T-type, currents in
      dissociated neurons from the rat dorsal root ganglion, superior cervical
      ganglion, and hippocampus. The widely used Kv channel blockers, including
      tetraethylammonium, alpha-dendrotoxin, phrixotoxin-2, and BDS-I, did not mimic or
      alter the effect of 4-AP on HVACCs. In HEK293 cells expressing various
      combinations of N-type (Cav2.2) channel subunits, 4-AP potentiated Ca(2+)
      currents primarily through the intracellular beta(3) subunit. In contrast, 4-AP
      had no effect on Cav3.2 channels expressed in HEK293 cells. Furthermore, blocking
      Kv channels did not mimic or change the potentiating effects of 4-AP on
      neurotransmitter release from sensory and motor nerve terminals. Thus, our
      findings challenge the conventional view that 4-AP facilitates synaptic and
      neuromuscular transmission by blocking Kv channels. Aminopyridines can directly
      target presynaptic HVACCs to potentiate neurotransmitter release independent of
      Kv channels.

PMID- 19850920
TI  - The transient receptor potential channels TRPP2 and TRPC1 form a heterotetramer
      with a 2:2 stoichiometry and an alternating subunit arrangement.
AB  - There is functional evidence that polycystin-2 (TRPP2) interacts with other
      members of the transient receptor potential family, including TRPC1 and TRPV4.
      Here we have used atomic force microscopy to study the structure of the TRPP2
      homomer and the interaction between TRPP2 and TRPC1. The molecular volumes of
      both Myc-tagged TRPP2 and V5-tagged TRPC1 isolated from singly transfected tsA
      201 cells indicated that they assembled as homotetramers. The molecular volume of
      the protein isolated from cells expressing both TRPP2 and TRPC1 was intermediate
      between the volumes of the two homomers, suggesting that a heteromer was being
      formed. The distribution of angles between pairs of anti-Myc antibodies bound to
      TRPP2 particles had a large peak close to 90 degrees and a smaller peak close to
      180 degrees , consistent with the assembly of TRPP2 as a homotetramer. In
      contrast, the corresponding angle distributions for decoration of the TRPP2-TRPC1
      heteromer by either anti-Myc or anti-V5 antibodies had predominant peaks close to
      180 degrees . This decoration pattern indicates a TRPP2:TRPC1 subunit
      stoichiometry of 2:2 and an alternating subunit arrangement.

PMID- 19850921
TI  - REH2 RNA helicase in kinetoplastid mitochondria: ribonucleoprotein complexes and
      essential motifs for unwinding and guide RNA (gRNA) binding.
AB  - Regulation of gene expression in kinetoplastid mitochondria is largely post
      transcriptional and involves the orchestration of polycistronic RNA processing,
      3'-terminal maturation, RNA editing, turnover, and translation; however, these
      processes remain poorly studied. Core editing complexes and their U
      insertion/deletion activities are relatively well characterized, and a battery of
      ancillary factors has recently emerged. This study characterized a novel DExH-box
      RNA helicase, termed here REH2 (RNA editing associated helicase 2), in unique
      ribonucleoprotein complexes that exhibit unwinding and guide RNA binding
      activities, both of which required a double-stranded RNA-binding domain (dsRBD)
      and a functional helicase motif I of REH2. REH2 complexes and recently identified
      related particles share a multiprotein core but are distinguished by several
      differential polypeptides. Finally, REH2 associates transiently, via RNA, with
      editing complexes, mitochondrial ribosomes, and several ancillary factors that
      control editing and RNA stability. We propose that these putative higher order
      structures coordinate mitochondrial gene expression.

PMID- 19850922
TI  - Crystal structure of a "nonfoldable" insulin: impaired folding efficiency despite
      native activity.
AB  - Protein evolution is constrained by folding efficiency ("foldability") and the
      implicit threat of toxic misfolding. A model is provided by proinsulin, whose
      misfolding is associated with beta-cell dysfunction and diabetes mellitus. An
      insulin analogue containing a subtle core substitution (Leu(A16) --> Val) is
      biologically active, and its crystal structure recapitulates that of the wild
      type protein. As a seeming paradox, however, Val(A16) blocks both insulin chain
      combination and the in vitro refolding of proinsulin. Disulfide pairing in
      mammalian cell culture is likewise inefficient, leading to misfolding,
      endoplasmic reticular stress, and proteosome-mediated degradation. Val(A16)
      destabilizes the native state and so presumably perturbs a partial fold that
      directs initial disulfide pairing. Substitutions elsewhere in the core similarly
      destabilize the native state but, unlike Val(A16), preserve folding efficiency.
      We propose that Leu(A16) stabilizes nonlocal interactions between nascent alpha
      helices in the A- and B-domains to facilitate initial pairing of Cys(A20) and
      Cys(B19), thus surmounting their wide separation in sequence. Although Val(A16)
      is likely to destabilize this proto-core, its structural effects are mitigated
      once folding is achieved. Classical studies of insulin chain combination in vitro
      have illuminated the impact of off-pathway reactions on the efficiency of native
      disulfide pairing. The capability of a polypeptide sequence to fold within the
      endoplasmic reticulum may likewise be influenced by kinetic or thermodynamic
      partitioning among on- and off-pathway disulfide intermediates. The properties of
      [Val(A16)]insulin and [Val(A16)]proinsulin demonstrate that essential
      contributions of conserved residues to folding may be inapparent once the native
      state is achieved.

PMID- 19850923
TI  - RhoE inhibits 4E-BP1 phosphorylation and eIF4E function impairing cap-dependent
      translation.
AB  - The Rho GTPase family member RhoE inhibits RhoA/ROCK signaling to promote actin
      stress fiber and focal adhesion disassembly. We have previously reported that
      RhoE also inhibits cell cycle progression and Ras-induced transformation,
      specifically preventing cyclin D1 translation. Here we investigate the molecular
      mechanisms underlying those observations. RhoE inhibits the phosphorylation of
      the translational repressor 4E-BP1 in response to extracellular stimuli. However,
      RhoE does not affect the activation of mTOR, the major kinase regulating 4E-BP1
      phosphorylation, as indicated by the phosphorylation levels of the mTOR substrate
      S6K, the dynamics of mTOR/Raptor association, and the observation that RhoE, as
      opposed to rapamycin, does not impair cellular growth. Interestingly, RhoE
      prevents the release of the eukaryotic initiation factor eIF4E from 4E-BP1,
      inhibiting cap-dependent translation. Accordingly, RhoE also inhibits the
      expression and the transcriptional activity of the eIF4E target c-Myc. Consistent
      with its crucial role in cell proliferation, we show that eIF4E can rescue both
      cell cycle progression and Ras-induced transformation in RhoE-expressing cells,
      indicating that the inhibition of eIF4E function is critical to mediate the anti
      proliferative effects of RhoE.

PMID- 19850924
TI  - Mutagenesis alters the catalytic mechanism of the light-driven enzyme
      protochlorophyllide oxidoreductase.
AB  - The light-activated enzyme protochlorophyllide oxidoreductase (POR) catalyzes an
      essential step in the synthesis of the most abundant pigment on Earth,
      chlorophyll. This unique reaction involves the sequential addition of a hydride
      and proton across the C17=C18 double bond of protochlorophyllide (Pchlide) by
      dynamically coupled quantum tunneling and is an important model system for
      studying the mechanism of hydrogen transfer reactions. In the present work, we
      have combined site-directed mutagenesis studies with a variety of sensitive
      spectroscopic and kinetic measurements to provide new insights into the
      mechanistic role of three universally conserved Cys residues in POR. We show that
      mutation of Cys-226 dramatically alters the catalytic mechanism of the enzyme. In
      contrast to wild-type POR, the characteristic charge-transfer intermediate,
      formed upon hydride transfer from NADPH to the C17 position of Pchlide, is absent
      in C226S variant enzymes. This suggests a concerted hydrogen transfer mechanism
      where proton transfer only is rate-limiting. Moreover, Pchlide reduction does not
      require the network of solvent-coupled conformational changes that play a key
      role in the proton transfer step of wild-type POR. We conclude that this globally
      important enzyme is finely tuned to facilitate efficient photochemistry, and the
      removal of a key interaction with Pchlide in the C226S variants significantly
      affects the local active site structure in POR, resulting in a shorter donor
      acceptor distance for proton transfer.

PMID- 19850925
TI  - Complement factor H binds at two independent sites to C-reactive protein in acute
      phase concentrations.
AB  - Factor H (FH) regulates the activation of C3b in the alternative complement
      pathway, both in serum and at host cell surfaces. It is composed of 20 short
      complement regulator (SCR) domains. The Y402H polymorphism in FH is a risk factor
      for age-related macular degeneration. C-reactive protein (CRP) is an acute phase
      protein that binds Ca(2+). We established the FH-CRP interaction using improved
      analytical ultracentrifugation (AUC), surface plasmon resonance (SPR), and
      synchrotron x-ray scattering methods. Physiological FH and CRP concentrations
      were used in 137 mM NaCl and 2 mM Ca(2+), in which the occurrence of denatured
      CRP was avoided. In solution, AUC revealed FH-CRP binding. The FH-CRP interaction
      inhibited the formation of higher FH oligomers, indicating that CRP blocked FH
      dimerization sites at both SCR-6/8 and SCR-16/20. SPR confirmed the FH-CRP
      interaction and its NaCl concentration dependence upon using either immobilized
      FH or CRP. The SCR-1/5 fragment of FH did not bind to CRP. In order of increasing
      affinity, SCR-16/20, SCR-6/8 (His-402), and SCR-6/8 (Tyr-402) fragments bound to
      CRP. X-ray scattering showed that FH became more compact when binding to CRP,
      which is consistent with CRP binding at two different FH sites. We concluded that
      FH and CRP bind at elevated acute phase concentrations of CRP in physiological
      buffer. The SCR-16/20 site is novel and indicates the importance of the FH-CRP
      interaction for both age-related macular degeneration and atypical hemolytic
      uremic syndrome.

PMID- 19850927
TI  - Human IgG1 hinge fragmentation as the result of H2O2-mediated radical cleavage.
AB  - Hinge cleavage of a recombinant human IgG1 antibody, generated during production
      in a Chinese hamster ovary cell culture, was observed in the purified material.
      The cleavage products could be reproduced by incubation of the antibody with
      H(2)O(2) and featured complementary ladders of the C- and N-terminal residues
      (Asp(226)-Lys(227)-Thr(228)-His(229)-Thr(230)) in the heavy chain of the Fab
      domain and the upper hinge of one of the Fc domains, respectively. Two adducts of
      +45 and +71 Da were also observed at the N-terminal residues of some Fc fragments
      and were identified as isocyanate and alpha-ketoacyl derivatives generated by
      radical cleavage at the alpha-carbon position through the diamide and alpha
      amidation pathways. We determined that the hinge cleavage was initiated by
      radical-induced breakage of the disulfide bond between the two hinge cysteines at
      position 231 (Cys(231)-Pro-Pro-Cys-Pro), followed by the formation of a thiyl
      radical (Cys(231)-S(*)) on one cysteine and sulfenic acid (Cys(231)-SOH) on the
      other. The location of the initial radical attack and the critical role of
      Cys(231) were demonstrated by the observation that 5,5-dimethyl-1-pyrroline N
      oxide only reacted with the Cys(231) radical and completely blocked hinge
      cleavage, suggesting the necessity of an electron/radical transfer from the
      Cys(231) radical to the hinge residues where cleavage was observed. As a
      precursor of hydroxyl radicals, H(2)O(2) is widely produced in healthy cells and
      tissues and therefore could be the source for the radical-induced fragmentation
      of human IgG1 antibodies in vivo.

PMID- 19850926
TI  - Mutation in the heparan sulfate biosynthesis enzyme EXT1 influences growth factor
      signaling and fibroblast interactions with the extracellular matrix.
AB  - Heparan sulfate (HS) chains bind and modulate the signaling efficiency of many
      ligands, including members of the fibroblast growth factor (FGF) and platelet
      derived growth factor families. We previously reported the structure of HS
      synthesized by embryonic fibroblasts from mice with a gene trap mutation of Ext1
      that encodes a glycosyltransferase involved in HS chain elongation. The gene trap
      mutation results in low expression of Ext1, and, as a consequence, HS chain
      length is substantially reduced. In the present study, Ext1 mutant and wild-type
      mouse embryonic fibroblasts were analyzed for the functional consequences of the
      Ext1 mutation for growth factor signaling and interaction with the extracellular
      matrix. Here, we show that the phosphorylation of ERK1/2 in response to FGF2
      stimulation was markedly decreased in the Ext1 mutant fibroblasts, whereas
      neither PDGF-BB nor FGF10 signaling was significantly affected. Furthermore, Ext1
      mutants displayed reduced ability to attach to collagen I and to contract
      collagen lattices, even though no differences in the expression of collagen
      binding integrins were observed. Reintroduction of Ext1in the Ext1 mutant
      fibroblasts rescued HS chain length, FGF2 signaling, and the ability of the
      fibroblasts to contract collagen. These data suggest that the length of the HS
      chains is a critical determinant of HS-protein interactions and emphasize the
      essential role of EXT1 in providing specific binding sites for growth factors and
      extracellular matrix proteins.

PMID- 19850928
TI  - Designed auto-assembly of nanostreptabodies for rapid tissue-specific targeting
      in vivo.
AB  - Molecular medicine can benefit greatly from antibodies that deliver therapeutic
      and imaging agents to select organs and diseased tissues. Yet the development of
      complex and defined composite nanostructures remains a challenge that requires
      both designed stoichiometric assembly and superior in vivo testing ability. Here,
      we generate nanostructures called nanostreptabodies by controlled sequential
      assembly of biotin-engineered antibody fragments on a streptavidin scaffold with
      a defined capacity for additional biotinylated payloads such as other antibodies
      to create bispecific antibodies as well as organic and non-organic moieties. When
      injected intravenously, these novel and stable nanostructures exhibit exquisite
      targeting with tissue-specific imaging and delivery, including rapid
      transendothelial transport that enhances tissue penetration. This "tinkertoy
      construction" strategy provides a very flexible and efficient way to link
      targeting vectors with reporter and/or effector agents, thereby providing
      virtually endless combinations potentially useful for multipurpose molecular and
      functional imaging in vivo as well as therapies.

PMID- 19850929
TI  - The Hsp90 inhibitor geldanamycin abrogates colocalization of eIF4E and eIF4E
      transporter into stress granules and association of eIF4E with eIF4G.
AB  - The eukaryotic translation initiation factor eIF4E plays a critical role in the
      control of translation initiation through binding to the mRNA 5' cap structure.
      eIF4E is also a component of processing bodies and stress granules, which are two
      types of cytoplasmic RNA granule in which translationally inactivated mRNAs
      accumulate. We found that treatment with the Hsp90 inhibitor geldanamycin leads
      to a substantial reduction in the number of HeLa cells that contain processing
      bodies. In contrast, stress granules are not disrupted but seem to be only
      partially affected by the inhibition of Hsp90. However, it is striking that eIF4E
      as well as its binding partner eIF4E transporter (4E-T), which mediates the
      import of eIF4E into the nucleus, are obviously lost from stress granules.
      Furthermore, the amount of eIF4G that is associated with the cap via eIF4E is
      reduced by geldanamycin treatment. Thus, the chaperone activity of Hsp90 probably
      contributes to the correct localization of eIF4E and 4E-T to stress granules and
      also to the interaction between eIF4E and eIF4G, both of which may be needed for
      eIF4E to acquire the physiological functionality that underlies the mechanism of
      translation initiation.

PMID- 19850930
TI  - Reduction of beta-amyloid levels by novel protein kinase C(epsilon) activators.
AB  - Isoform-specific protein kinase C (PKC) activators may be useful as therapeutic
      agents for the treatment of Alzheimer disease. Three new epsilon-specific PKC
      activators, made by cyclopropanation of polyunsaturated fatty acids, have been
      developed. These activators, AA-CP4, EPA-CP5, and DHA-CP6, activate PKCepsilon in
      a dose-dependent manner. Unlike PKC activators that bind to the 1,2
      diacylglycerol-binding site, such as bryostatin and phorbol esters, which produce
      prolonged down-regulation, the new activators produced sustained activation of
      PKC. When applied to cells expressing human APPSwe/PS1delta, which produce large
      quantities of beta-amyloid peptide (Abeta), DCP-LA and DHA-CP6 reduced the
      intracellular and secreted levels of Abeta by 60-70%. In contrast to the marked
      activation of alpha-secretase produced by PKC activators in fibroblasts, the PKC
      activators produced only a moderate and transient activation of alpha-secretase
      in neuronal cells. However, they activated endothelin-converting enzyme to 180%
      of control levels, suggesting that the Abeta-lowering ability of these PKCepsilon
      activators is caused by increasing the rate of Abeta degradation by endothelin
      converting enzyme and not by activating nonamyloidogenic amyloid precursor
      protein metabolism.

PMID- 19850931
TI  - Constitutive reactive oxygen species generation from autophagosome/lysosome in
      neuronal oxidative toxicity.
AB  - Reactive oxygen species (ROS) are involved in several cell death processes,
      including cerebral ischemic injury. We found that glutamate-induced ROS
      accumulation and the associated cell death in mouse hippocampal cell lines were
      delayed by pharmacological inhibition of autophagy or lysosomal activity.
      Glutamate, however, did not stimulate autophagy, which was assessed by a protein
      marker, LC3, and neither changes in organization of mitochondria nor lysosomal
      membrane permeabilization were observed. Fluorescent analyses by a redox probe PF
      H(2)TMRos revealed that autophagosomes and/or lysosomes are the major sites for
      basal ROS generation in addition to mitochondria. Treatments with inhibitors for
      autophagy and lysosomes decreased their basal ROS production and caused a burst
      of mitochondrial ROS to be delayed. On the other hand, attenuation of
      mitochondrial activity by serum depletion or by high cell density culture
      resulted in the loss of both constitutive ROS production and an ROS burst in
      mitochondria. Thus, constitutive ROS production within mitochondria and lysosomes
      enables cells to be susceptible to glutamate-induced oxidative cytotoxicity.
      Likewise, inhibitors for autophagy and lysosomes reduced neural cell death in an
      ischemia model in rats. We suggest that cell injury during periods of ischemia is
      regulated by ROS-generating activity in autophagosomes and/or lysosomes as well
      as in mitochondria.

PMID- 19850932
TI  - Phosphatidylinositol 3-kinase signaling does not activate the wnt cascade.
AB  - Mutational activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs
      in a wide variety of tumors, whereas activating Wnt pathway mutants are
      predominantly found in colon cancer. Because GSK3 is a key component of both
      pathways, it is widely assumed that active PI3K signaling feeds positively into
      the Wnt pathway by protein kinase B (PKB)-mediatefd inhibition of GSK3. In
      addition, PKB has been proposed to modulate the canonical Wnt signaling through
      direct stabilization and nuclear localization of beta-catenin. Here, we show that
      compartmentalization by Axin of GSK3 prohibits cross-talk between the PI3K and
      Wnt pathways and that Wnt-mediated transcriptional activity is not modulated by
      activation of the PI3K/PKB pathway.

PMID- 19850933
TI  - Sequestosome-1/p62 is the key intracellular target of innate defense regulator
      peptide.
AB  - Innate defense regulator-1 (IDR-1) is a synthetic peptide with no antimicrobial
      activity that enhances microbial infection control while suppressing
      inflammation. Previously, the effects of IDR-1 were postulated to impact several
      regulatory pathways including mitogen-activated protein kinase (MAPK) p38 and
      CCAAT-enhancer-binding protein, but how this was mediated was unknown. Using a
      combined stable isotope labeling by amino acids in cell culture-proteomics
      methodology, we identified the cytoplasmic scaffold protein p62 as the molecular
      target of IDR-1. Direct IDR-1 binding to p62 was confirmed by several biochemical
      binding experiments, and the p62 ZZ-type zinc finger domain was identified as the
      IDR-1 binding site. Co-immunoprecipitation analysis of p62 molecular complexes
      demonstrated that IDR-1 enhanced the tumor necrosis factor alpha-induced p62
      receptor-interacting protein 1 (RIP1) complex formation but did not affect tumor
      necrosis factor alpha-induced p62-protein kinase zeta complex formation. In
      addition, IDR-1 induced p38 MAPK activity in a p62-dependent manner and increased
      CCAAT-enhancer-binding protein beta activity, whereas NF-kappaB activity was
      unaffected. Collectively, these results demonstrate that IDR-1 binding to p62
      specifically affects protein-protein interactions and subsequent downstream
      events. Our results implicate p62 in the molecular mechanisms governing innate
      immunity and identify p62 as a potential therapeutic target in both infectious
      and inflammatory diseases.

PMID- 19850934
TI  - Epigenetic gene silencing by the SRY protein is mediated by a KRAB-O protein that
      recruits the KAP1 co-repressor machinery.
AB  - The sex determination transcription factor SRY is a cell fate-determining
      transcription factor that mediates testis differentiation during embryogenesis.
      It may function by repressing the ovarian determinant gene, RSPO1, action in the
      ovarian developmental pathway and activates genes, such as SOX9, important for
      testis differentiation at the onset of gonadogenesis. Further, altered expression
      of SRY and related SOX genes contribute to oncogenesis in many human cancers.
      Little is known of the mechanisms by which SRY regulates its target genes.
      Recently a KRAB domain protein (KRAB-O) that lacks a zinc finger motif has been
      demonstrated to interact with SRY and hypothesized to function as an adaptor
      molecule for SRY by tethering the KAP1-NuRD-SETDB1-HP1 silencing machinery to
      repress SRY targets. We have critically examined this hypothesis by
      reconstituting and characterizing SRY-KRAB-O-KAP1 interactions. These recombinant
      molecules can form a ternary complex by direct and high affinity interactions.
      The KRAB-O protein can simultaneously bind KAP1 and SRY in a noncompetitive but
      also noncooperative manner. An extensive mutagenesis analysis suggests that
      different surfaces on KRAB-O are utilized for these independent interactions.
      Transcriptional repression by SRY requires binding to KRAB-O, thus bridging to
      the KAP1 repression machinery. This repression machinery is recruited to SRY
      target promoters in chromatin templates via SRY. These results suggest that SRY
      has co-opted the KRAB-O protein to recruit the KAP1 repression machinery to sex
      determination target genes. Other KRAB domain proteins, which lack a zinc finger
      DNA-binding motif, may function in similar roles as adaptor proteins for
      epigenetic gene silencing.

PMID- 19850935
TI  - Perilipin controls lipolysis by regulating the interactions of AB-hydrolase
      containing 5 (Abhd5) and adipose triglyceride lipase (Atgl).
AB  - The mobilization of stored lipid by hormones is a fundamental function of fat
      cells, and there is strong evidence that perilipin (Plin), a lipid droplet
      scaffold, and adipose tissue triglyceride lipase (Atgl), a triglyceride-specific
      lipase, play critical roles. Previous work suggested that Abhd5, a protein
      activator of Atgl, coordinates with Plin in controlling basal and stimulated
      lipolysis; however, the underlying mechanism is controversial. The present
      experiments investigated protein trafficking and interactions among Plin, Atgl,
      and Abhd5 in live cells. The results demonstrate that Plin binds Abhd5 with high
      affinity and thereby suppresses the interaction of Abhd5 with Atgl. Sequestration
      of Abhd5 appears to a major mechanism by which Plin reduces basal lipolysis.
      Phosphorylation of Plin on serine 492 or serine 517 rapidly releases Abhd5 from
      Plin, allowing Abhd5 to directly interact with Atgl. Imaging experiments
      demonstrated that the Plin-dependent interaction of Abhd5 and Atgl occurs mainly,
      but not exclusively, on lipid droplets that contain Plin.

PMID- 19850936
TI  - The alpha-secretase-derived N-terminal product of cellular prion, N1, displays
      neuroprotective function in vitro and in vivo.
AB  - Cellular prion protein (PrP(c)) undergoes a disintegrin-mediated physiological
      cleavage, generating a soluble amino-terminal fragment (N1), the function of
      which remained unknown. Recombinant N1 inhibits staurosporine-induced caspase-3
      activation by modulating p53 transcription and activity, whereas the PrP(c)
      derived pathological fragment (N2) remains biologically inert. Furthermore, N1
      protects retinal ganglion cells from hypoxia-induced apoptosis, reduces the
      number of terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end
      labeling-positive and p53-immunoreactive neurons in a pressure-induced ischemia
      model of the rat retina and triggers a partial recovery of b-waves but not a
      waves of rat electroretinograms. Our work is the first demonstration that the
      alpha-secretase-derived PrP(c) fragment N1, but not N2, displays in vivo and in
      vitro neuroprotective function by modulating p53 pathway. It further demonstrates
      that distinct N-terminal cleavage products of PrP(c) harbor different biological
      activities underlying the various phenotypes linking PrP(c) to cell survival.

PMID- 19850937
TI  - Zinc protoporphyrin regulates cyclin D1 expression independent of heme oxygenase
      inhibition.
AB  - Zinc protoporphyrin IX (ZnPP), an endogenous heme analogue that inhibits heme
      oxygenase (HO) activity, represses tumor growth. It can also translocate into the
      nucleus and up-regulate heme oxygenase 1 (HMOX1) gene expression. Here, we
      demonstrate that tumor cell proliferation was inhibited by ZnPP, whereas tin
      protoporphyrin (SnPP), another equally potent HO-1 inhibitor, had no effect.
      Microarray analysis on 128 tumorigenesis related genes showed that ZnPP
      suppressed genes involved in cell proliferation and angiogenesis. Among these
      genes, CYCLIN D1 (CCND1) was specifically inhibited as were its mRNA and protein
      levels. Additionally, ZnPP inhibited CCND1 promoter activity through an Sp1 and
      Egr1 overlapping binding site (S/E). We confirmed that ZnPP modulated the S/E
      site, at least partially by associating with Sp1 and Egr1 proteins rather than
      direct binding to DNA targets. Furthermore, administration of ZnPP significantly
      inhibited cyclin D1 expression and progression of a B-cell leukemia/lymphoma 1
      tumor in mice by preferentially targeting tumor cells. These observations show HO
      independent effects of ZnPP on cyclin D1 expression and tumorigenesis.

PMID- 19850938
TI  - Secretory phospholipase A2, group IIA is a novel serum amyloid A target gene:
      activation of smooth muscle cell expression by an interleukin-1 receptor
      independent mechanism.
AB  - Atherosclerosis is a multifactorial vascular disease characterized by formation
      of inflammatory lesions. Elevated circulating acute phase proteins indicate
      disease risk. Serum amyloid A (SAA) is one such marker but its function remains
      unclear. To determine the role of SAA on aortic smooth muscle cell gene
      expression, a preliminary screen of a number of genes was performed and a strong
      up-regulation of expression of secretory phospholipase A(2), group IIA (sPLA(2))
      was identified. The SAA-induced increase in sPLA(2) was validated by real time
      PCR, Western blot analysis, and enzyme activity assays. Demonstrating that SAA
      increased expression of sPLA(2) heteronuclear RNA and that inhibiting
      transcription eliminated the effect of SAA on sPLA(2) mRNA suggested that the
      increase was transcriptional. Transient transfections and electrophoretic
      mobility shift assays identified CAAT enhancer-binding protein (C/EBP) and
      nuclear factor kappaB (NFkappaB) as key regulatory sites mediating the induction
      of sPLA(2). Moreover, SAA activated the inhibitor of NF-kappaB kinase (IKK) in
      cultured smooth muscle cells. Previous reports showed that interleukin (IL)-1beta
      up-regulates Pla2g2a gene transcription via C/EBPbeta and NFkappaB.
      Interestingly, SAA activated smooth muscle cell IL-1beta mRNA expression,
      however, blocking IL-1 receptors had no effect on SAA-mediated activation of
      sPLA(2) expression. Thus, the observed changes in sPLA(2) expression were not
      secondary to SAA-induced IL-1 receptor activation. The association of SAA with
      high density lipoprotein abrogated the SAA-induced increase in sPLA(2)
      expression. These data suggest that during atherogenesis, SAA can amplify the
      involvement of smooth muscle cells in vascular inflammation and that this can
      lead to deposition of sPLA(2) and subsequent local changes in lipid homeostasis.

PMID- 19850939
TI  - Shift to an involvement of phosphatidylinositol 3-kinase in angiotensin II
      actions on nucleus tractus solitarii neurons of the spontaneously hypertensive
      rat.
AB  - RATIONALE: Central angiotensin (Ang) II inhibits baroreflex and plays an
      important role in the pathogenesis of hypertension. However, the underlying
      molecular mechanisms are still not fully understood. OBJECTIVE: Our objective in
      the present study was to characterize the signal transduction mechanism of
      phosphatidylinositol 3-kinase (PI3K) involvement in Ang II-induced stimulation of
      central neuronal activity in cultured neurons and Ang II-induced inhibition of
      baroreflex in spontaneously hypertensive rats (SHR) versus WKY rats. METHODS AND
      RESULTS: Application of Ang II to neurons produced a 42% greater increase in
      neuronal firing in cells from the SHR than the WKY rat. Although the Ang II
      mediated increase in firing rate was abolished entirely by the protein kinase
      (PK)C inhibitor GF109230 in the WKY, blockade of both PKC and PI3K activity was
      necessary in the SHR. This was associated with an increased ability of Ang II to
      stimulate NADPH oxidase-reactive oxygen species (ROS)-mediated signaling
      involving phosphorylation of the p47phox subunit of the NADPH oxidase and was
      dependent on the activation of PI3K in the SHR. Inhibition of PI3K resulted in
      the reduction of levels of p47phox phosphorylation, NADPH oxidase activity, ROS
      levels, and ultimately neuronal activity in cells from the SHR but not the WKY
      rat. In addition, in working heart-brainstem preparations, inhibition of PKC
      activity in the nucleus of the solitary tract in situ abolished the Ang II
      mediated depression of cardiac and sympathetic baroreceptor reflex gain in the
      WKY. In contrast, PKC inhibition in the nucleus of the solitary tract of SHR only
      partially reduced the effect of Ang II on the baroreceptor reflex gain.
      CONCLUSIONS: These observations demonstrate that PI3K in the cardiovascular
      brainstem regions of the SHR may be selectively involved in Ang II-mediated
      signaling that includes a reduction in baroreceptor reflex function, presumably
      via a NADPH-ROS mediated pathway.

PMID- 19850940
TI  - Left ventricular and myocardial function in mice expressing constitutively
      pseudophosphorylated cardiac troponin I.
AB  - RATIONALE: Protein kinase (PK)C-induced phosphorylation of cardiac troponin
      (cTn)I has been shown to regulate cardiac contraction. OBJECTIVE: Characterize
      functional effects of increased PKC-induced cTnI phosphorylation and identify
      underlying mechanisms using a transgenic mouse model (cTnI(PKC-P)) expressing
      mutant cTnI (S43E, S45E, T144E). METHODS AND RESULTS: Two-dimensional gel
      analysis showed 7.2+/-0.5% replacement of endogenous cTnI with the mutant form.
      Experiments included: mechanical measurements (perfused isolated hearts, isolated
      papillary muscles, and skinned fiber preparations), biochemical and molecular
      biological measurements, and a mathematical model-based analysis for integrative
      interpretation. Compared to wild-type mice, cTnI(PKC-P) mice exhibited negative
      inotropy in isolated hearts (14% decrease in peak developed pressure), papillary
      muscles (53% decrease in maximum developed force), and skinned fibers (14%
      decrease in maximally activated force, F(max)). Additionally, cTnI(PKC-P) mice
      exhibited slowed relaxation in both isolated hearts and intact papillary muscles.
      The cTnI(PKC-P) mice showed no differences in calcium sensitivity, cooperativity,
      steady-state force-MgATPase relationship, calcium transient (amplitude and
      relaxation), or baseline phosphorylation of other myofilamental proteins. The
      model-based analysis revealed that experimental observations in cTnI(PKC-P) mice
      could be reproduced by 2 simultaneous perturbations: a decrease in the rate of
      cross-bridge formation and an increase in calcium-independent persistence of the
      myofilament active state. CONCLUSIONS: A modest increase in PKC-induced cTnI
      phosphorylation ( approximately 7%) can significantly alter cardiac muscle
      contraction: negative inotropy via decreased cross-bridge formation and negative
      lusitropy via persistence of myofilament active state. Based on our data and data
      from the literature we speculate that effects of PKC-mediated cTnI
      phosphorylation are site-specific (S43/S45 versus T144).

PMID- 19850941
TI  - Angiotensin II-induced oxidative stress resets the Ca2+ dependence of Ca2+
      calmodulin protein kinase II and promotes a death pathway conserved across
      different species.
AB  - RATIONALE: Angiotensin (Ang) II-induced apoptosis was reported to be mediated by
      different signaling molecules. Whether these molecules are either interconnected
      in a single pathway or constitute different and alternative cascades by which Ang
      II exerts its apoptotic action, is not known. OBJECTIVE: To investigate in
      cultured myocytes from adult cat and rat, 2 species in which Ang II has opposite
      inotropic effects, the signaling cascade involved in Ang II-induced apoptosis.
      METHODS AND RESULTS: Ang II (1 micromol/L) reduced cat/rat myocytes viability by
      approximately 40%, in part, because of apoptosis (TUNEL/caspase-3 activity). In
      both species, apoptosis was associated with reactive oxygen species (ROS)
      production, Ca(2+)/calmodulin-dependent protein kinase (CaMK)II, and p38 mitogen
      activated protein kinase (p38MAPK) activation and was prevented by the ROS
      scavenger MPG (2-mercaptopropionylglycine) or the NADPH oxidase inhibitor DPI
      (diphenyleneiodonium) by CaMKII inhibitors (KN-93 and AIP [autocamtide 2-related
      inhibitory peptide]) or in transgenic mice expressing a CaMKII inhibitory peptide
      and by the p38MAPK inhibitor, SB202190. Furthermore, p38MAPK overexpression
      exacerbated Ang II-induced cell mortality. Moreover, although KN-93 did not
      affect Ang II-induced ROS production, it prevented p38MAPK activation. Results
      further show that CaMKII can be activated by Ang II or H(2)O(2), even in the
      presence of the Ca(2+) chelator BAPTA-AM, in myocytes and in EGTA-Ca(2+)-free
      solutions in the presence of the calmodulin inhibitor W-7 in in vitro
      experiments. CONCLUSIONS: (1) The Ang II-induced apoptotic cascade converges in
      both species, in a common pathway mediated by ROS-dependent CaMKII activation
      which results in p38MAPK activation and apoptosis. (2) In the presence of Ang II
      or ROS, CaMKII may be activated at subdiastolic Ca(2+) concentrations, suggesting
      a new mechanism by which ROS reset the Ca(2+) dependence of CaMKII to extremely
      low Ca(2+) levels.

PMID- 19850942
TI  - Antioxidant amelioration of dilated cardiomyopathy caused by conditional deletion
      of NEMO/IKKgamma in cardiomyocytes.
AB  - RATIONALE: Insight into the function of nuclear factor (NF)-kappaB in the adult
      heart has been hampered by the embryonic lethality of constitutive NF-kappaB
      inactivation. OBJECTIVE: The goal of the present study was therefore to gain
      insights into the role of NF-kappaB pathway specifically in mouse cardiomyocytes
      by conditional deletion of the NF-kappaB essential modulator (NEMO). METHODS AND
      RESULTS: Using a Cre/loxP system, we disrupted the Nemo gene in a cardiomyocyte
      specific manner in the heart, which simulated gene expression changes underlying
      human heart failure and caused adult-onset dilated cardiomyopathy accompanied by
      inflammation and apoptosis. Pressure overload challenges of NEMO-deficient young
      hearts precociously induced the functional decrements that develop spontaneously
      in older knockout animals. Moreover, oxidative stress in NEMO-deficient
      cardiomyocytes is a critical pathological component that can be attenuated with
      antioxidant diet in vivo. CONCLUSIONS: These results reveal an essential
      physiological role for NEMO-mediated signaling in the adult heart to maintain
      cardiac function in response to age-related or mechanical challenges, in part
      through modulation of oxidative stress.

PMID- 19850943
TI  - Blockade of Hsp20 phosphorylation exacerbates cardiac ischemia/reperfusion injury
      by suppressed autophagy and increased cell death.
AB  - RATIONALE: The levels of a small heat shock protein (Hsp)20 and its
      phosphorylation are increased on ischemic insults, and overexpression of Hsp20
      protects the heart against ischemia/reperfusion injury. However, the mechanism
      underlying cardioprotection of Hsp20 and especially the role of its
      phosphorylation in regulating ischemia/reperfusion-induced autophagy, apoptosis,
      and necrosis remain to be clarified. OBJECTIVE: Herein, we generated a cardiac
      specific overexpression model, carrying nonphosphorylatable Hsp20, where serine
      16 was substituted with alanine (Hsp20(S16A)). By subjecting this model to
      ischemia/reperfusion, we addressed whether: (1) the cardioprotective effects of
      Hsp20 are associated with serine 16 phosphorylation; (2) blockade of Hsp20
      phosphorylation influences the balance between autophagy and cell death; and (3)
      the aggregation pattern of Hsp20 is altered by its phosphorylation. METHODS AND
      RESULTS: Our results demonstrated that Hsp20(S16A) hearts were more sensitive to
      ischemia/reperfusion injury, evidenced by lower recovery of contractile function
      and increased necrosis and apoptosis, compared with non-TG hearts. Interestingly,
      autophagy was activated in non-TG hearts but significantly inhibited in
      Hsp20(S16A) hearts following ischemia/reperfusion. Accordingly, pretreatment of
      Hsp20(S16A) hearts with rapamycin, an activator of autophagy, resulted in
      improvement of functional recovery, compared with saline-treated Hsp20(S16A)
      hearts. Furthermore, on ischemia/reperfusion, the oligomerization pattern of
      Hsp20 appeared to shift to higher aggregates in Hsp20(S16A) hearts. CONCLUSIONS:
      Collectively, these data indicate that blockade of Ser16-Hsp20 phosphorylation
      attenuates the cardioprotective effects of Hsp20 against ischemia/reperfusion
      injury, which may be attributable to suppressed autophagy and increased cell
      death. Therefore, phosphorylation of Hsp20 at serine 16 may represent a potential
      therapeutic target in ischemic heart disease.

PMID- 19850944
TI  - beta2-Adrenergic receptor gene polymorphism is associated with mortality in
      septic shock.
AB  - RATIONALE: The CysGlyGln haplotype of the beta(2)-adrenergic receptor gene
      (ADRB2) is functional and associated with altered responses to adrenergic
      agonists in patients with asthma. Whether this functional haplotype alters
      outcome in patients receiving adrenergic agonists in septic shock is unknown.
      OBJECTIVES: To determine whether genetic variation of ADRB2 influences outcome in
      septic shock. METHODS: Two cohorts of patients with septic shock were studied: a
      single center (St. Paul's Hospital [SPH]) cohort (n = 589) and the Vasopressin
      and Septic Shock Trial (VASST) cohort (n = 616). The A allele of the rs1042717
      G/A polymorphism is in complete linkage disequilibrium with the CysGlyGln
      haplotype of ADRB2; therefore, rs1042717 was genotyped. Modulation by
      norepinephrine and salbutamol of IL-6 production by stimulated in vitro
      lymphoblastoid cells was measured by genotype. MEASUREMENTS AND MAIN RESULTS:
      Patients who had the AA genotype of rs1042717 displayed increased 28-day
      mortality in SPH (adjusted hazard ratio, 2.23; 95% confidence interval, 1.33
      3.72; P = 0.0022), and this result was replicated in VASST (adjusted hazard ratio
      2.82; 95% confidence interval, 1.56-5.09; P = 0.0006). This genotypic effect was
      eliminated in patients treated with acute low-dose corticosteroids. In all
      patients, the AA genotype was associated with more organ dysfunction. Patients
      with the AA genotype had a higher heart rate (SPH; P < 0.05; VASST; P < 0.05) and
      required a higher norepinephrine dose over Days 1 through 3 (VASST; P < 0.05).
      The AA genotype was associated with decreased norepinephrine and salbutamol
      inhibition of IL-6 production by stimulated lymphoblastoid cells in vitro (P <
      0.05). CONCLUSIONS: The AA genotype of ADRB2 rs1042717, identifying homozygotes
      for the CysGlyGln haplotype, was associated with increased mortality and more
      organ dysfunction in septic shock.

PMID- 19850945
TI  - In utero smoke exposure and role of maternal and infant glutathione s-transferase
      genes on airway responsiveness and lung function in infancy.
AB  - RATIONALE: Xenobiotics in the maternal circulation are capable of crossing the
      placental barrier so a reduction in the mother and fetus's detoxification ability
      due to genetic variation in the glutathione S-transferases (GSTs) could expose
      the fetus to higher levels of toxins. OBJECTIVES: To investigate the interactive
      effects of maternal smoking during pregnancy with maternal and infant GST
      genotypes on airway responsiveness (AR) and lung function in infancy. METHODS:
      GSTT1, GSTP1 and GSTM1 were genotyped in infants and mothers, in utero smoke
      exposure was evaluated by questionnaire, AR was assessed by histamine challenge
      and Vmax(FRC) was measured using the rapid thoracoabdominal compression
      technique. We investigated the interactive effects of maternal smoking during
      pregnancy with maternal and infant GST genes on AR and lung function at 1, 6, and
      12 months and longitudinally throughout the first year. MEASUREMENTS AND MAIN
      RESULTS: Infant and/or maternal GSTT1 nonnull was associated with reduced AR at
      12 months and throughout the first year and increased Vmax(FRC) at 6 months.
      Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(FRC) at 6
      months. In infants exposed to in utero smoke, infant and/or maternal GSTT1
      nonnull was associated with reduced AR at 1 month and throughout the first year
      and increased Vmax(FRC) throughout the first year. Maternal GSTP1 Val/Val or
      Ile/Val was associated with increased Vmax(FRC) at 6 months. CONCLUSIONS: GST
      genes may be especially important during fetal development as they may modify,
      through proficient detoxification, the effects of in utero maternal smoke
      exposure on AR and lung function in infants.

PMID- 19850946
TI  - Role of epidermal growth factor inhibition in experimental pulmonary
      hypertension.
AB  - RATIONALE: Epidermal growth factor (EGF) and its receptors play a role in cell
      proliferation and survival and are implicated in the pathobiology of pulmonary
      arterial hypertension (PAH). OBJECTIVES: To study the role of EGF inhibition on
      experimental pulmonary hypertension. METHODS: We investigated (1) the effects of
      three clinically approved EGF receptor (EGFR) antagonists in vitro on rat
      pulmonary arterial smooth muscle cell proliferation and in vivo on experimental
      pulmonary hypertension (PH) induced by monocrotaline injection in rats and by
      chronic hypoxia in mice, and (2) the expression of EGFR in the lung tissues from
      experimental and clinical PH. MEASUREMENTS AND MAIN RESULTS: The EGFR inhibitors
      gefitinib, erlotinib, and lapatinib inhibited the EGF-induced proliferation of
      pulmonary arterial smooth muscle cells. In rats with established PH, gefitinib
      and erlotinib significantly reduced right ventricular systolic pressure and right
      ventricular hypertrophy. In addition, the medial wall thickness and
      muscularization of pulmonary arteries were improved. In contrast, lapatinib did
      not provide therapeutic benefit. These EGFR antagonists at their highest
      tolerable dose did not yield significant improvement in right ventricular
      systolic pressure, right ventricular hypertrophy, and pulmonary vascular
      remodeling in mice with chronic hypoxic PH. Moreover, no significant alteration
      in the EGFR expression was detected in the lung tissues from patients with
      idiopathic PAH. CONCLUSIONS: The partial therapeutic efficacy of the EGFR
      antagonists in animal models of pulmonary hypertension and the absence of
      significant alteration in EGFR expression in the lungs from patients with
      idiopathic PAH suggest that EGFRs do not represent a promising target for the
      treatment of pulmonary hypertension.

PMID- 19850948
TI  - Matrix metalloproteinase-8 and the regulation of blood pressure, vascular
      inflammation, and atherosclerotic lesion growth.

PMID- 19850947
TI  - Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis.
AB  - RATIONALE: Ineffective repair of a damaged alveolar epithelium has been
      postulated to cause pulmonary fibrosis. In support of this theory, epithelial
      cell abnormalities, including hyperplasia, apoptosis, and persistent denudation
      of the alveolar basement membrane, are found in the lungs of humans with
      idiopathic pulmonary fibrosis and in animal models of fibrotic lung disease.
      Furthermore, mutations in genes that affect regenerative capacity or that cause
      injury/apoptosis of type II alveolar epithelial cells have been identified in
      familial forms of pulmonary fibrosis. Although these findings are compelling,
      there are no studies that demonstrate a direct role for the alveolar epithelium
      or, more specifically, type II cells in the scarring process. OBJECTIVES: To
      determine if a targeted injury to type II cells would result in pulmonary
      fibrosis. METHODS: A transgenic mouse was generated to express the human
      diphtheria toxin receptor on type II alveolar epithelial cells. Diphtheria toxin
      was administered to these animals to specifically target the type II epithelium
      for injury. Lung fibrosis was assessed by histology and hydroxyproline
      measurement. MEASUREMENTS AND MAIN RESULTS: Transgenic mice treated with
      diphtheria toxin developed an approximately twofold increase in their lung
      hydroxyproline content on Days 21 and 28 after diphtheria toxin treatment. The
      fibrosis developed in conjunction with type II cell injury. Histological
      evaluation revealed diffuse collagen deposition with patchy areas of more
      confluent scarring and associated alveolar contraction. CONCLUSIONS: The
      development of lung fibrosis in the setting of type II cell injury in our model
      provides evidence for a causal link between the epithelial defects seen in
      idiopathic pulmonary fibrosis and the corresponding areas of scarring.

PMID- 19850950
TI  - Feasibility and acceptability of a school-based coping intervention for Latina
      adolescents.
AB  - Latino girls (Latinas) experience disproportionate rates of emotional distress,
      including suicidal ideation, which may be indicative of inadequate coping
      abilities. Prevention of mental health problems, a U.S. public health priority,
      is particularly critical for Latina adolescents due to lack of access to mental
      health treatments. The purpose of this study was to examine the feasibility of
      Project Wings, a 14-session stress management/coping intervention. Latinas in
      school (ages 15-21) met weekly for 2-hr with two bilingual experienced
      facilitators to participate in sharing circles, relaxation exercise, and skill
      building. Intervention participation and post-intervention focus group data were
      analyzed. Fall semester intervention (n = 10) occurred during school (72%
      attendance rate); spring semester intervention (n = 11) was after school (84%
      attendance rate). Focus group data confirmed acceptability. Latina adolescents
      will participate in a school-based, group-based stress management/coping
      intervention. The findings offer insights about intervention recruitment and
      retention that are specifically relevant to school nurses. Future research
      includes intervention testing using a randomized study design.

PMID- 19850951
TI  - Management of primary dysmenorrhea by school adolescents in ILE-IFE, Nigeria.
AB  - Dysmenorrhea is a problem that girls and women face and often manage themselves
      with or without support from health professionals. A cross-sectional, descriptive
      study was conducted among adolescents with dysmenorrhea (N = 150) in Ile-Ife,
      Nigeria. The aims of the study were to determine their knowledge of menstruation
      and primary dysmenorrhea, assess the severity of pain they experienced during an
      episode of primary dysmenorrhea, and determine the management strategies they
      adopted. A pre-tested semi-structured questionnaire was used to collect data.
      Findings revealed the adolescents had a knowledge deficit regarding menstruation
      and dysmenorrhea, 58% of respondents reported pain between face 4 and face 10 on
      the Faces Pain Scale and the majority used inappropriate methods to manage
      primary dysmenorrhea. School nurses are able to assist adolescents and their
      mothers in proper management of primary dysmenorrhea.

PMID- 19850952
TI  - Sixth-grade boys' perceived benefits of and barriers to physical activity and
      suggestions for increasing physical activity.
AB  - Interventions are needed to reduce the high overweight prevalence noted among
      boys in early high school. Because decreased physical activity (PA) is a factor
      for weight gain and a decline in boys' PA occurs across the middle school years,
      a need exists to intervene, as soon as boys reach middle school, to help them get
      adequate PA. The purpose of this study was to explore perceived benefits,
      barriers, self-efficacy, enjoyment or activity preferences, and situational or
      environmental influences related to PA among sixth-grade boys (N = 40). Each boy
      participated in one of seven focus groups. Having an average weight was the most
      important benefit. The most prominent personal barrier focused on being
      unmotivated. Environmental barriers included lacking equipment and places for PA.
      Suggestions for increasing boys' PA were identified. Findings have implications
      for nurses interested in designing interventions to assist boys of this age in
      achieving PA recommendations.

PMID- 19850949
TI  - The emerging characterization of lysine residue deacetylation on the modulation
      of mitochondrial function and cardiovascular biology.
AB  - There is emerging recognition of a novel fuel and redox sensing regulatory
      program that controls cellular adaptation via nonhistone protein lysine residue
      acetyl posttranslation modifications. This program functions in tissues with high
      energy demand and oxidative capacity and is highly enriched in the heart.
      Deacetylation is regulated by NAD(+)-dependent activation of the sirtuin family
      of proteins, whereas acetyltransferase modifications are controlled by less
      clearly delineated acetyltransferases. Subcellular localization specific protein
      targets of lysine-acetyl modification have been identified in the nucleus,
      cytoplasm, and mitochondria. Despite distinct subcellular localizations, these
      modifications appear, in large part, to modify mitochondrial properties including
      respiration, energy production, apoptosis, and antioxidant defenses. These
      mitochondrial regulatory programs are important in cardiovascular biology,
      although how protein acetyl modifications effects cardiovascular pathophysiology
      has not been extensively explored. This review will introduce the role of
      nonhistone protein lysine residue acetyl modifications, discuss their regulation
      and biochemistry and present the direct and indirect data implicating their
      involvement in the heart and vasculature.

PMID- 19850953
TI  - The comorbidity of ADHD in the general population of Saudi Arabian school-age
      children.
AB  - OBJECTIVE: To investigate comorbidity of oppositional-defiant disorder (ODD),
      conduct disorder (CD), anxiety, and depression and to investigate the impaired
      social and academic developments among children with ADHD in primary school
      settings in Saudi Arabia. METHOD: Data for the purpose of this study are obtained
      from parent and teachers of 652 primary school children attending Grades 1 to 3
      (children aged between 7 and 9 years). Vanderbilt ADHD diagnostic rating scale,
      which has relevance and found to be reliable by previous studies, is used in the
      study. RESULTS: ODD and CD are reported to be present in close to two thirds
      (73%) of children with ADHD, as assessed with DSM-IV-TR criteria. Anxiety and
      depression disorder are estimated to be present in 36% of children with ADHD.
      Children with ADHD show high levels of impairment in academic achievements (63%)
      and social performance (90%), compared with non-ADHD children. CONCLUSION: These
      findings suggest that a significant minority of disruptive children may have
      their difficulties compounded by the presence of ADHD, which raises the question
      whether their problems are known and whether they have received appropriate help.
      It is important to develop a specific set of psychological clinical intervention
      for helping children with ADHD, ODD, CD, and other related problems. Educating
      teachers and parents about ADHD and its comorbidity is considered essential in
      this regard.

PMID- 19850954
TI  - Phosphorylation of nephrin triggers its internalization by raft-mediated
      endocytosis.
AB  - Proper localization of nephrin determines integrity of the glomerular slit
      diaphragm. Slit diaphragm proteins assemble into functional signaling complexes
      on a raft-based platform, but how the trafficking of these proteins coordinates
      with their signaling function is unknown. Here, we demonstrate that a raft
      mediated endocytic (RME) pathway internalizes nephrin. Nephrin internalization
      was slower with raft-mediated endocytosis than with classic clathrin-mediated
      endocytosis. Ultrastructurally, the RME pathway consisted of noncoated
      invaginations and was dependent on cholesterol and dynamin. Nephrin constituted a
      stable, signaling-competent microdomain through interaction with Fyn, a Src
      kinase, and podocin, a scaffold protein. Tyrosine phosphorylation of nephrin
      triggered its own RME-mediated internalization. Protamine-induced
      hyperphosphorylation of nephrin led to noncoated invaginations predominating over
      coated pits. These results demonstrate that an RME pathway couples nephrin
      internalization to its own signaling, suggesting that RME promotes proper
      spatiotemporal assembly of slit diaphragms during podocyte development or injury.

PMID- 19850955
TI  - Left ventricular geometry predicts cardiovascular outcomes associated with anemia
      correction in CKD.
AB  - Partial correction of anemia in patients with chronic kidney disease (CKD)
      reduces left ventricular hypertrophy (LVH), which is a risk factor for
      cardiovascular (CV) morbidity, but complete correction of anemia does not improve
      CV outcomes. Whether LV geometry associates with CV events in patients who are
      treated to different hemoglobin (Hb) targets is unknown. One of the larger trials
      to study the effects of complete correction of anemia in stages 3 to 4 CKD was
      the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta
      (CREATE) trial. Here, we analyzed echocardiographic data from CREATE to determine
      the prevalence, dynamics, and prognostic implications of abnormal LV geometry in
      patients who were treated to different Hb targets. The prevalence of LVH at
      baseline was 47%, with eccentric LVH more frequent than concentric. During the
      study, LVH prevalence and mean left ventricular mass index did not change
      significantly, but LV geometry fluctuated considerably within 2 yr in both
      groups. CV event-free survival was significantly worse in the presence of
      concentric LVH and eccentric LVH compared with the absence of LVH (P = 0.0009 and
      P < or = 0.0001, respectively). Treatment to the higher Hb target associated with
      reduced event-free survival in the subgroup with eccentric LVH at baseline (P =
      0.034). In conclusion, LVH is common and associates with poor outcomes among
      patients with stages 3 to 4 CKD, although both progression and regression of
      abnormal LV geometry occur. Complete anemia correction may aggravate the adverse
      prognosis of eccentric LVH.

PMID- 19850957
TI  - How to tell a new story about battering.
AB  - As Evan Stark observes, getting domestic violence against women recognized as
      coercive control will require a major effort of storytelling. Women's accounts of
      subjugation have to be narrated in a way that is both true to their experiences
      and capable of eliciting public understanding, sympathy, and action. This essay
      draws on an interdisciplinary literature on narrative to show why doing that
      poses such a formidable challenge. In lieu of the tragic form that has dominated
      battered women's storytelling, and in lieu of the quest and mystery forms that
      appear in Stark's own accounts, this article argues for using a rebirth story
      line.This genre, which has affinities with the fairytales Snow White and Sleeping
      Beauty, seems an unlikely vehicle for asserting battered women's combination of
      victimization and agency. Drawing on the stories told by battered women as part
      of a successful reform effort, however, this article shows how women have used
      the form effectively.

PMID- 19850956
TI  - Cystin localizes to primary cilia via membrane microdomains and a targeting
      motif.
AB  - Primary cilia are dynamic, complex structures that contain >500 proteins,
      including several related to polycystic kidney disease. How these proteins target
      to cilia and assemble is unknown. We previously identified Cys1 as the gene
      responsible for disease in Cys1(cpk) mice, a mouse model of autosomal recessive
      polycystic kidney disease; this gene encodes cystin, a 145-amino acid cilium
      associated protein. Here, we characterized the localization of cystin in the
      embryonic kidney and liver, in isolated renal collecting ducts, and in an inner
      medullary collecting duct mouse cell line. Because endogenous levels of cystin
      expression are low, we generated inner medullary collecting duct cell lines that
      stably express enhanced green fluorescence protein-tagged constructs of wild-type
      cystin or various truncation mutants. We determined that cystin is myristoylated
      at its G2 residue and that N-myristoylated cystin fractionates with membrane
      microdomains. Furthermore, the N-myristoylation signal is necessary but not
      sufficient to target cystin to the primary cilium. Analysis of deletion and
      chimeric constructs identified an AxEGG motif that is necessary to target and
      retain cystin in the cilium. Derangement of these localization motifs may lead to
      cystic kidney disease.

PMID- 19850958
TI  - "How would that help our work?": the intersection of domestic violence and human
      rights in the United States.
AB  - This qualitative study explores whether individuals working within the domestic
      violence (DV) field in the United States have utilized a human rights framework
      and identifies potential benefits of this framework. Using the critique and
      experiences of women of color as a focal point, data were gathered through
      interviews with key individuals working with national and regional DV and human
      rights organizations. This article focuses on challenges within the mainstream DV
      movement and how a human rights approach could potentially ameliorate some of
      these concerns by supporting a more holistic approach to DV and increasing
      coalition building and community engagement.

PMID- 19850959
TI  - Rethinking Coercive Control.
AB  - The critical appraisals of Coercive Control focus largely on what my analysis
      implies for intervention, a matter to which the book devotes only limited space.
      In this reply, I reiterate core concepts in the book and acknowledge that much
      more work is needed to translate the realities of coercive control into practical
      legal and advocacy strategies. I review how coercive control differs from partner
      assaults and so why it merits a distinct response; the extent to which coercive
      control targets gender identity; the wisdom of complementing the focus on
      violence with an emphasis on male domination, sexual inequality and personal
      liberty; what this implies for shelters and the law; why sexual inequality
      differentiates coercive control from female partner abuse of men; how sexual
      equality can be both cause and antidote for coercive control; why I think an
      affirmative concept of freedom is essential to grasp the human rights violations
      inflicted by coercive control; and what it means to "story" coercive control by
      integrating women into the larger liberty narrative on which our national
      identity rests.

PMID- 19850961
TI  - Diagnosis of occupational asthma from time point differences in serial PEF
      measurements.
AB  - BACKGROUND: The diagnosis of occupational asthma requires objective confirmation.
      Analysis of serial measurements of peak expiratory flow (PEF) is usually the most
      convenient first step in the diagnostic process. A new method of analysis
      originally developed to detect late asthmatic reactions following specific
      inhalation testing is described. This was applied to serial PEF measurements made
      over many days in the workplace to supplement existing methods of PEF analysis.
      METHODS: 236 records from workers with independently diagnosed occupational
      asthma and 320 records from controls with asthma were available. The pooled
      standard deviation for rest day measurements was obtained from an analysis of
      variance by time. Work day PEF measurements were meaned into matching 2-hourly
      time segments. Time points with mean work day PEF statistically lower (at the
      Bonferroni adjusted 5% level) than the rest days were counted after adjusting for
      the number of contributing measurements. RESULTS: A minimum of four time point
      comparisons were needed. Records with >or=2 time points significantly lower on
      work days had a sensitivity of 67% and a specificity of 99% for the diagnosis of
      occupational asthma against independent diagnoses. Reducing the requirements to
      >or=1 non-waking time point difference increased sensitivity to 77% and reduced
      specificity to 93%. The analysis was only applicable to 43% of available records,
      mainly due to differences in waking times on work and rest days. CONCLUSION: Time
      point analysis complements other validated methods of PEF analysis for the
      diagnosis of occupational asthma. It requires shorter records than are required
      for the Oasys score and can identify smaller changes than other methods, but is
      dependent on low rest day PEF variance.

PMID- 19850960
TI  - Gut microbes define liver cancer risk in mice exposed to chemical and viral
      transgenic hepatocarcinogens.
AB  - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) frequently results from
      synergism between chemical and infectious liver carcinogens. Worldwide, the
      highest incidence of HCC is in regions endemic for the foodborne contaminant
      aflatoxin B1 (AFB1) and hepatitis B virus (HBV) infection. Recently, gut microbes
      have been implicated in multisystemic diseases including obesity and diabetes.
      Here, the hypothesis that specific intestinal bacteria promote liver cancer was
      tested in chemical and viral transgenic mouse models. METHODS: Helicobacter-free
      C3H/HeN mice were inoculated with AFB1 and/or Helicobacter hepaticus. The
      incidence, multiplicity and surface area of liver tumours were quantitated at 40
      weeks. Molecular pathways involved in tumourigenesis were analysed by microarray,
      quantitative real-time PCR, liquid chromatography/mass spectrometry, ELISA,
      western blot and immunohistochemistry. In a separate experiment, C57BL/6 FL-N/35
      mice harbouring a full-length hepatitis C virus (HCV) transgene were crossed with
      C3H/HeN mice and cancer rates compared between offspring with and without H
      hepaticus. RESULTS: Intestinal colonisation by H hepaticus was sufficient to
      promote aflatoxin- and HCV transgene-induced HCC. Neither bacterial translocation
      to the liver nor induction of hepatitis was necessary. From its preferred niche
      in the intestinal mucus layer, H hepaticus activated nuclear factor-kappaB (NF
      kappaB)-regulated networks associated with innate and T helper 1 (Th1)-type
      adaptive immunity both in the lower bowel and liver. Biomarkers indicative of
      tumour progression included hepatocyte turnover, Wnt/beta-catenin activation and
      oxidative injury with decreased phagocytic clearance of damaged cells.
      CONCLUSIONS: Enteric microbiota define HCC risk in mice exposed to carcinogenic
      chemicals or hepatitis virus transgenes. These results have implications for
      human liver cancer risk assessment and prevention.

PMID- 19850962
TI  - SNAI transcription factors mediate epithelial-mesenchymal transition in lung
      fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung
      disease characterised by accumulation of activated (myo)fibroblasts and excessive
      extracellular matrix deposition. The enhanced accumulation of (myo)fibroblasts
      may be attributed, in part, to the process of transforming growth factor beta1
      (TGFbeta1)-induced epithelial-mesenchymal transition (EMT), the phenotypic
      switching of epithelial to fibroblast-like cells. Although alveolar epithelial
      type II (ATII) cells have been shown to undergo EMT, the precise mediators and
      mechanisms remain to be resolved. The objective of this study is to investigate
      the role of SNAI transcription factors in the process of EMT and in IPF. METHODS:
      Using quantitative reverse transcription-PCR (RT-PCR), immunofluorescence,
      immunohistochemistry, western blotting, as well as gain- and loss-of-function
      studies and functional assays, the role of SNAI1 and SNAI2 in TGFbeta1-induced
      EMT in ATII cells in vitro was assessed; and the expression of SNAI transcription
      factors was analysed in experimental and human IPF in vivo. RESULTS: TGFbeta1
      treatment increased the expression and nuclear accumulation of SNAI1 and SNAI2,
      in concert with induction of EMT in ATII cells. SNAI overexpression was
      sufficient to induce EMT, and small interfering RNA (siRNA)-mediated SNAI
      depletion attenuated TGFbeta1-induced ATII cell migration and EMT. SNAI
      expression was elevated in experimental and human IPF and localised to
      hyperplastic ATII cells in vivo. CONCLUSIONS: The results demonstrate that
      TGFbeta1-induced EMT in ATII cells is essentially controlled by the expression
      and nuclear translocation of SNAI transcription factors. Increased SNAI1 and
      SNAI2 expression in experimental and human IPF in vivo suggests that SNAI
      mediated EMT may contribute to the fibroblast pool in idiopathic pulmonary
      fibrosis.

PMID- 19850964
TI  - Upper airway function and arousability to ventilatory challenge in slow wave
      versus stage 2 sleep in obstructive sleep apnoea.
AB  - Patients with obstructive sleep apnoea (OSA) have reduced event rates during slow
      wave sleep (SWS) compared with stage 2 sleep. To explore this phenomenon,
      ventilatory and arousal timing responses to partial and complete airflow
      obstruction during SWS versus stage 2 sleep were examined. METHODS: Ten patients,
      mean+/-SD apnoea-hypopnoea index (AHI) 49.7+/-16.5 events/h with reduced OSA
      frequency during SWS (SWS AHI 18.9+/-14.0 events/h) slept with an epiglottic
      pressure catheter and nasal mask/pneumotachograph. Patients underwent rapid
      continuous positive airway pressure (CPAP) dialdowns to three subtherapeutic
      levels and brief airway occlusions in random order. RESULTS: Post-dialdown, there
      were marked reductions in peak flow and minute ventilation, and progressive
      increases in inspiratory effort (p<0.001), but with limited ventilatory recovery
      and no differences between sleep stages. CPAP versus peak flow relationships on
      the third and second to last breath pre-arousal were not different between sleep
      stages. Arousals occurred later and post-dialdown arousal probability was lower
      during SWS compared with stage 2 sleep, Cox hazard ratio (95% CI) 0.65 (0.48 to
      0.88), p=0.006. During SWS occlusions, time to arousal (mean+/-SEM) was prolonged
      (23.0+/-2.6 vs 17.1+/-1.7 s, p=0.02). Inspiratory effort developed more rapidly (
      1.0+/-0.2 vs -0.6+/-0.1 cm H(2)O/s, p=0.019) and was more negative (-28.7+/-2.7
      vs -20.3+/-1.6 cm H(2)O, p<0.001) on the breath preceding arousal. CONCLUSIONS:
      Except for a heightened ventilatory drive response during airway occlusion,
      airway function and ventilatory compensation to ventilatory challenge appear to
      be similar, but with consistently and substantially delayed arousal responses, in
      SWS versus stage 2 sleep.

PMID- 19850963
TI  - Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low
      income cohort.
AB  - BACKGROUND: Acetaminophen has been associated with asthma and is in part
      metabolised via the glutathione pathway. Inner-city minority children have high
      asthma morbidity and a relatively high frequency of a minor allele variant in the
      glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal
      acetaminophen exposure would predict wheeze at age 5 years in an inner-city
      minority cohort and examined whether this association was modified by common
      polymorphisms in genes related to the glutathione pathway. METHODS: An ongoing
      population-based birth cohort study of Dominican Republic and African-American
      children in New York prospectively assessed the use of analgesics during
      pregnancy and current wheeze at age 5 years in 301 children. Genotyping was
      conducted for GST polymorphisms. Binomial regression was used to adjust for
      potential confounders including postnatal acetaminophen use. RESULTS: 34% of
      mothers reported acetaminophen use during pregnancy and 27% of children had
      current wheeze at 5 years. Prenatal exposure to acetaminophen predicted current
      wheeze (multivariate relative risk 1.71; 95% CI 1.20 to 2.42; p=0.003), and the
      risk increased monotonically with increasing number of days of prenatal
      acetaminophen exposure (p trend <0.001). 68% of children had at least one copy of
      the GSTP1 minor allele (Val). The risk of wheeze was modified by GSTP1 (additive
      interaction p=0.009) and was observed only among children with the GSTP1 minor
      allele. CONCLUSIONS: Prenatal exposure to acetaminophen predicted wheeze at age 5
      years in an inner-city minority cohort. The risk was modified by a functional
      polymorphism in GSTP1, suggesting a mechanism involving the glutathione pathway.

PMID- 19850965
TI  - Increase in extrapulmonary tuberculosis in England and Wales 1999-2006.
AB  - BACKGROUND: Extrapulmonary tuberculosis appears to be increasing in England and
      Wales. The trends in extrapulmonary tuberculosis and factors associated with
      these trends were examined. METHODS: National tuberculosis surveillance data from
      1999-2006 for England and Wales were used, including demographic, clinical and
      laboratory information. Trends in the proportion of tuberculosis cases with
      extrapulmonary disease were investigated using the chi(2) trend test and
      associated factors using logistic regression. RESULTS: Among all the cases of
      tuberculosis, the proportion with extrapulmonary disease increased from 48% in
      1999 (2717 cases) to 53% in 2006 (4205 cases, p<0.001). Regression analysis
      showed that the rise in extrapulmonary disease was associated with an increase in
      the proportion of non-UK born cases (odds ratio 2.7, 95% CI 2.6 to 2.8). A more
      than threefold increase was observed in the proportion of all tuberculosis cases
      with miliary tuberculosis from 0.7% of all cases (38 cases) to 2.2% (180 cases,
      p<0.001). This rise was not associated with changes in place of birth or in any
      of the other risk factors identified. CONCLUSIONS: The proportion of cases with
      extrapulmonary disease has increased over the study period. To a large extent
      this is due to an increasing proportion of non-UK born cases. Reasons for the
      rise in miliary tuberculosis require further investigation. Clinicians should
      have a higher index of clinical suspicion of extrapulmonary tuberculosis in non
      UK born cases.

PMID- 19850966
TI  - TNFalpha-induced GM-CSF release from human airway smooth muscle cells depends on
      activation of an ET-1 autoregulatory positive feedback mechanism.
AB  - BACKGROUND: There is an urgent need to inhibit endothelin-1 (ET-1) induced
      chronic inflammatory processes in early stages of lung diseases in order to
      prevent untreatable irreversible stages often accompanied by lung fibrosis and
      pulmonary hypertension. Nothing is known about the airway inflammation-inducing
      and/or maintaining role of ET-1 in human airway smooth muscle cells (HASMCs).
      OBJECTIVE: ET-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF)
      expression in response to tumour necrosis factor alpha (TNFalpha) and ET-1
      stimulation was investigated, and the impact of mitogen-activated protein kinase
      (MAPK) pathways in this context was studied. To elucidate the anti-inflammatory
      properties of the dual endothelin receptor antagonist bosentan that targets both
      endothelin receptor subtypes A (ET(A)R) and B (ET(B)R), its effect on the
      TNFalpha/ET-1/GM-CSF network was investigated. METHODS: ET-1 and GM-CSF
      expression and activation of MAPKs were investigated via quantitative reverse
      transcription-PCR (RT-PCR), western blotting and ELISA. MAIN RESULTS: Both
      TNFalpha and ET-1 activated p38(MAPK) and extracellular signal-regulated kinase
      (ERK)-1/-2 signalling. ET-1 expression was induced by TNFalpha and by ET-1
      itself. Both effects were inhibited by bosentan and by specific ET(A)R or
      p38(MAPK) blockade. ET-1- and TNFalpha-induced GM-CSF expression were both
      reduced by bosentan as well as by specific inhibition of either ET(A)R, ET(B)R,
      p38(MAPK) or ERK-1/-2. CONCLUSION: TNFalpha activates an ET(A)R- and p38(MAPK)
      dependent ET-1 autoregulatory positive feedback loop to maintain GM-CSF release
      from HASMCs. Since bosentan impairs ET-1 autoregulation and TNFalpha-induced ET-1
      release, as well as TNFalpha- and ET-1-induced GM-CSF release, the present data
      suggest therapeutic utility for bosentan in treating particularly the early
      stages of chronic inflammatory airway diseases.

PMID- 19850967
TI  - Neurotransmission in lower esophageal sphincter of W/Wv mutant mice.
AB  - To address the controversy surrounding the role of interstitial cells of Cajal
      (ICC) in nitrergic neurotransmission to gastrointestinal smooth muscle, circular
      smooth muscle from the lower esophageal sphincter (LES) of W/W(v) wild-type and
      mutant (ICC-deficient) mice were studied by using intracellular and tension
      recordings in vitro. Resting membrane potential was more negative, and the
      spontaneous unitary potentials diminished in mutant mice. In wild-type mice,
      nerve stimulation induced a biphasic inhibitory junction potential (IJP)
      consisting of a fast initial IJP followed by a long-lasting slow IJP (LSIJP). The
      IJP was markedly impaired in a significant proportion of mutant mice, whereas in
      others it was normal. Pharmacological studies in the mice with markedly impaired
      IJPs revealed that cholinergic and purinergic components of the nerve-mediated
      responses appeared intact. In wild-type mice, caffeine hyperpolarized smooth
      muscle cells, inhibited the initial fast IJP, and completely abolished the LSIJP.
      In mutant mice, caffeine depolarized smooth muscle cells and abolished the
      impaired LSIJP but did not affect the initial fast IJP. Immunohistochemical
      staining for c-Kit confirmed deficiency of ICC in mutant mice with a normal
      nitrergic IJP. Rings of LES circular smooth muscle from W/W(v) mutant mice
      generated significantly less spontaneous tone than controls. When tone was
      restored with carbachol, normal nitrergic LES relaxation was recorded. These data
      suggest that 1) there is significant variability in the generation of nitrergic
      neurotransmission in the LES of W/W(v) mutant mice, whereas purinergic and
      cholinergic neurotransmission are intact; 2) the altered nitrergic responses
      appear to be associated with abnormal Ca2+-dependent signaling initiated by
      spontaneous Ca2+ release from sarcoplasmic reticulum in smooth muscle cells; and
      3) c-Kit-positive ICC are not essential for nitrergic neurotransmission in mouse
      LES smooth muscle.

PMID- 19850970
TI  - [P-selectin and its role in some diseases].
AB  - P-selectin is an adhesion molecule located in the platelet a granule and Weibel
      Palade body of endothelial cells. P-selectin mediates the rolling of blood cells
      on the surface of the endothelium and initiates the attachment of leukocytes
      circulating in the blood to platelets, endothelial cells,and other leukocytes at
      sites of tissue injury and inflammation. These processes are possible because
      ligands for P-selectin are present on the surface of platelets and endothelial
      cells which undergo sulfation of a specific tyrosine residue at its N-terminal
      for P-selectin recognition. P-selectin glycoprotein ligand-1 (PSGL-1) is a major
      ligand for P-selectin which is responsible for leukocyte rolling on active
      endothelium. Glycoprotein GPIb mediates platelet adhesion to subendothelium at
      sites of injury and the rolling of inactivated platelets on its activated
      surface. Sulfatides are ligands for P-selectin, which plays a role in platelet
      aggregation and adhesion. Soluble P-selectin (sP-selectin) is presents in the
      blood and circulates in normal humans in concentrations of ca. 100 ng/ml. An
      increased level of sP-selectin is a major predictive factor of cardiovascular
      events related to platelet turnover and its activation and function. P-selectin
      plays a key role in diseases associated with injury and arterial thrombosis.
      Increased expression of P-selectin is observed in coronary artery disease, acute
      myocardial infarction, stroke, and peripheral artery diseases. The pathogenesis
      of thrombosis in cancer patients is related to dysfunction of endothelial cells,
      active involvement of leukocytes, and increased number and activity of platelets.
      Increased level of sP-selectin and elevated P-selectin expression may be good
      markers of some types of carcinoma,such as neoplastic pulmonary diseases, breast,
      renal, and colon cancer, and blood cancer.

PMID- 19850968
TI  - Inflammatory cells regulate p53 and caspases in acute pancreatitis.
AB  - The inflammatory response during pancreatitis regulates necrotic and apoptotic
      rates of parenchymal cells. Neutrophil depletion by use of anti-polymorphonuclear
      serum (anti-PMN) increases apoptosis in experimental pancreatitis but the
      mechanism has not been determined. Our study was designed to investigate
      signaling mechanisms in pancreatic parenchymal cells regulating death responses
      with neutrophil depletion. Rats were neutrophil depleted with anti-PMN treatment.
      Then cerulein pancreatitis was induced, followed by measurements of apoptosis
      signaling pathways. There was greater activation of executioner caspases-3 in the
      pancreas with anti-PMN treatment compared with control. There were no differences
      between these groups of animals in mitochondrial cytochrome c release or in
      activities of initiator caspase-8 and -9. However, there was greater activation
      of caspase-2 with anti-PMN treatment during cerulein pancreatitis. The upstream
      regulation of caspases-2 includes p53, which was increased; the p53 negative
      regulator, Mdm2, was decreased by anti-PMN treatment during cerulein
      pancreatitis. In vitro experiments using isolated pancreatic acinar cells a
      pharmacological inhibitor of Mdm2 increased caspase-2/-3 activities, and an
      inhibitor of p53 decreased these activities during cholecystokinin-8 treatment.
      Furthermore, experiments using the AR42J cell line Mdm2 small interfering RNA
      (siRNA) increased caspase-2/-3 activities, and p53 siRNA decreased these
      activities during cholecystokinin-8 treatment. These results suggest that during
      acute pancreatitis the inflammatory response inhibits apoptosis. The mechanism of
      this inhibition involves caspase-2 and its upstream regulation by p53 and Mdm2.
      Because previous findings indicate that promotion of apoptosis decreases necrosis
      and severity of pancreatitis, these results suggest that strategies to inhibit
      Mdm2 or activate p53 will have beneficial effects for treatment of pancreatitis.

PMID- 19850971
TI  - [The efficiency of the bactericidal action of serum raised by complement and
      lysozyme against bacteria which avoid the immunological response of higher
      organisms].
AB  - This paper presents some processes of the antibacterial effect of serum, which
      mainly results from the activities of complement (C) and lysozyme (muramidase,
      LZ). The C system consists ofa group of serum proteins and tissue fluids which
      are activated in a particular order. Complement,operating together with lysozyme,
      constitutes the main protection from microorganisms entering the body. Pathogenic
      microorganisms are able to avoid natural protective mechanisms by, among others,
      molecular mimicry, binding complement control proteins, or secreting proteolytic
      enzymes.The effectiveness of the cytolytic action of C proteins and LZ also
      depends on the surface structures of the microorganisms. Imbalance between the
      activation and deactivation of inflammatory reactions in the presence of
      pathogens can lead to various pathological states, such as autoimmunological
      diseases.

PMID- 19850972
TI  - Better fitting of cochlear implants: modeling loudness for acoustic and electric
      stimuli.
AB  - It is becoming more common for cochlear implant (CI) recipients to have some
      useful acoustic hearing post-operatively. Such CI users may benefit from
      simultaneous use of an acoustic hearing aid (HA). To provide a satisfactory
      fitting of both types of devices, it is helpful to make the loudness perceived
      via each device as similar as possible. In practice, this is usually attempted by
      adjusting the sensitivity and/or gain of each device during fitting, but it is
      often not clear whether or how well the loudness of the devices has been matched
      for each user. In this study, established numerical models of loudness for both
      acoustic and electric stimulation were used to investigate this problem. The
      models' outputs were compared to published psychophysical data and were found to
      approximate the main patterns observed in those data. They also showed that,
      theoretically, there would be differences in the loudness perceived with each
      type of device when sounds with varying frequency content and level were heard.
      Future sound processors and/or fitting techniques developed specifically for CI
      recipients with usable acoustic hearing could apply such computational models of
      loudness to improve simultaneous use of the two types of device.

PMID- 19850973
TI  - Encapsulated living choroid plexus cells: potential long-term treatments for
      central nervous system disease and trauma.
AB  - In neurodegenerative disease and in acute brain injury, there is often local up
      regulation of neurotrophin production close to the site of the lesion. Treatment
      by direct injection of neurotrophins and growth factors close to these lesion
      sites has repeatedly been demonstrated to improve recovery. It has therefore been
      proposed that transplanting viable neurotrophin-producing cells close to the
      trauma lesion, or site of degenerative disease, might provide a novel means for
      continuous delivery of these molecules directly to the site of injury or to a
      degenerative region. The aim of this paper is to summarize recent published
      information and present new experimental data that indicate that long-lasting
      therapeutic implants of choroid plexus (CP) neuroepithelium may be used to treat
      brain disease. CP produces and secretes numerous biologically active neurotrophic
      factors (NT). New gene microarray and proteomics data presented here indicate
      that many other anti-oxidant, anti-toxin and neuronal support proteins are also
      produced and secreted by CP cells. In the healthy brain, these circulate in the
      cerebrospinal fluid through the brain and spinal cord, maintaining neuronal
      networks and associated cells. Recent publications describe how transplanted CP
      cells and tissue, either free or in an immunoprotected encapsulated form, can
      effectively deliver therapeutic molecules when placed near the lesion or site of
      degenerative disease in animal models. Using simple techniques, CP
      neuroepithelial cell clusters in suspension culture were very durable, remaining
      viable for 6 months or more in vitro. The cell culture conditions had little
      effect on the wide range and activity of genes expressed and proteins secreted.
      Recently, completed experiments show that implanting CP within alginate-poly
      ornithine capsules effectively protected these xenogeneic cells from the host
      immune system and allowed their survival for 6 months or more in the brains of
      rats, causing no adverse effects. Previously reported evidence demonstrated that
      CP cells support the survival and differentiation of neuronal cells in vitro and
      effectively treat acute brain injury and disease in rodents and non-human
      primates in vivo. The accumulated preclinical data together with the long-term
      survival of implanted encapsulated cells in vivo provide a sound base for the
      investigation of these treatments for chronic inherited and established
      neurodegenerative conditions.

PMID- 19850974
TI  - Wireless technologies for closed-loop retinal prostheses.
AB  - In this paper, we discuss various technologies needed to develop retinal
      prostheses with wireless power and data telemetry operation. In addition to the
      need to communicate with the implanted device, supply of power to the retinal
      prosthesis is especially difficult. This is because, in the implanted state, the
      device is not fixed in position due to constant motion of the eye. Furthermore, a
      retinal prosthesis incorporating a high density electrode array of more than 1000
      electrodes is expected to consume approximately 45 mW of power and require 300
      kbps of image and stimulation data. The front end of the wireless power and data
      transmission, the antenna, needs to be small compared to the size of the eye.
      Also, the wireless module is expected to operate in the reactive near-field
      region due to small separation between the transmit and receive antennas compared
      to their size and corresponding operating wavelength. An inductive link is
      studied as a means to transfer power and for data telemetry between the implant
      and external unit. In this work, the use of integrated circuit and
      microfabrication technologies for implementing inductive links is discussed. A
      closed-loop approach is taken to improve performance and reach optimum operation
      condition. Design and simulation data are presented as the basis for development
      of viable wireless module prototypes.

PMID- 19850975
TI  - Development of a micromachined epiretinal vision prosthesis.
AB  - Microsystems engineering offers the tools to develop highly sophisticated
      miniaturized implants to interface with the nervous system. One challenging
      application field is the development of neural prostheses to restore vision in
      persons that have become blind by photoreceptor degeneration due to retinitis
      pigmentosa. The fundamental work that has been done in one approach is presented
      here. An epiretinal vision prosthesis has been developed that allows hybrid
      integration of electronics on one part of a thin and flexible substrate.
      Polyimide as a substrate material is proven to be non-cytotoxic. Non-hermetic
      encapsulation with parylene C was stable for at least 3 months in vivo. Chronic
      animal experiments proved spatially selective cortical activation after
      epiretinal stimulation with a 25-channel implant. Research results have been
      transferred successfully to companies that currently work on the medical device
      approval of these retinal vision prostheses in Europe and in the USA.

PMID- 19850977
TI  - Electrical stimulation promotes nerve cell differentiation on polypyrrole/poly (2
      methoxy-5 aniline sulfonic acid) composites.
AB  - The purpose of this work was to investigate for the first time the potential
      biomedical applications of novel polypyrrole (PPy) composites incorporating a
      large polyelectrolyte dopant, poly (2-methoxy-5 aniline sulfonic acid) (PMAS).
      The physical and electrochemical properties were characterized. The PPy/PMAS
      composites were found to be smooth and hydrophilic and have low electrical
      impedance. We demonstrate that PPy/PMAS supports nerve cell (PC12)
      differentiation, and that clinically relevant 250 Hz biphasic current pulses
      delivered via PPy/PMAS films significantly promote nerve cell differentiation in
      the presence of nerve growth factor (NGF). The capacity of PPy/PMAS composites to
      support and enhance nerve cell differentiation via electrical stimulation renders
      them valuable for medical implants for neurological applications.

PMID- 19850976
TI  - Neural prostheses and brain plasticity.
AB  - The success of modern neural prostheses is dependent on a complex interplay
      between the devices' hardware and software and the dynamic environment in which
      the devices operate: the patient's body or 'wetware'. Over 120 000
      severe/profoundly deaf individuals presently receive information enabling
      auditory awareness and speech perception from cochlear implants. The cochlear
      implant therefore provides a useful case study for a review of the complex
      interactions between hardware, software and wetware, and of the important role of
      the dynamic nature of wetware. In the case of neural prostheses, the most
      critical component of that wetware is the central nervous system. This paper will
      examine the evidence of changes in the central auditory system that contribute to
      changes in performance with a cochlear implant, and discuss how these changes
      relate to electrophysiological and functional imaging studies in humans. The
      relationship between the human data and evidence from animals of the remarkable
      capacity for plastic change of the central auditory system, even into adulthood,
      will then be examined. Finally, we will discuss the role of brain plasticity in
      neural prostheses in general.

PMID- 19850978
TI  - Neural synchrony in ventral cochlear nucleus neuron populations is not mediated
      by intrinsic processes but is stimulus induced: implications for auditory
      brainstem implants.
AB  - The aim of this investigation was to elucidate if neural synchrony forms part of
      the spike time-based theory for coding of sound information in the ventral
      cochlear nucleus (VCN) of the auditory brainstem. Previous research attempts to
      quantify the degree of neural synchrony at higher levels of the central auditory
      system have indicated that synchronized firing of neurons during presentation of
      an acoustic stimulus could play an important role in coding complex sound
      features. However, it is unknown whether this synchrony could in fact arise from
      the VCN as it is the first station in the central auditory pathway. Cross
      correlation analysis was conducted on 499 pairs of multiunit clusters recorded in
      the urethane-anesthetized rat VCN in response to pure tones and combinations of
      two tones to determine the presence of neural synchrony. The shift predictor
      correlogram was used as a measure for determining the synchrony owing to the
      effects of the stimulus. Without subtraction of the shift predictor, over 65% of
      the pairs of multiunit clusters exhibited significant correlation in neural
      firing when the frequencies of the tones presented matched their characteristic
      frequencies (CFs). In addition, this stimulus-evoked neural synchrony was
      dependent on the physical distance between electrode sites, and the CF difference
      between multiunit clusters as the number of correlated pairs dropped
      significantly for electrode sites greater than 800 microm apart and for multiunit
      cluster pairs with a CF difference greater than 0.5 octaves. However, subtraction
      of the shift predictor correlograms from the raw correlograms resulted in no
      remaining correlation between all VCN pairs. These results suggest that while
      neural synchrony may be a feature of sound coding in the VCN, it is stimulus
      induced and not due to intrinsic neural interactions within the nucleus. These
      data provide important implications for stimulation strategies for the auditory
      brainstem implant, which is used to provide functional hearing to the profoundly
      deaf through electrical stimulation of the VCN.

PMID- 19850979
TI  - Prototype to product-developing a commercially viable neural prosthesis.
AB  - The Cochlear implant or 'Bionic ear' is a device that enables people who do not
      get sufficient benefit from a hearing aid to communicate with the hearing world.
      The Cochlear implant is not an amplifier, but a device that electrically
      stimulates the auditory nerve in a way that crudely mimics normal hearing, thus
      providing a hearing percept. Many recipients are able to understand running
      speech without the help of lipreading. Cochlear implants have reached a stage of
      maturity where there are now 170 000 recipients implanted worldwide. The
      commercial development of these devices has occurred over the last 30 years. This
      development has been multidisciplinary, including audiologists, engineers, both
      mechanical and electrical, histologists, materials scientists, physiologists,
      surgeons and speech pathologists. This paper will trace the development of the
      device we have today, from the engineering perspective. The special challenges of
      designing an active device that will work in the human body for a lifetime will
      be outlined. These challenges include biocompatibility, extreme reliability,
      safety, patient fitting and surgical issues. It is emphasized that the successful
      development of a neural prosthesis requires the partnership of academia and
      industry.

PMID- 19850980
TI  - The 4th International Niigata Symposium on Diet and Health held on Nov 29-30,
      2008 in Niigata, Japan Title: "Integrated Functions of Diet in Anti-aging and
      Cancer Prevention".

PMID- 19850981
TI  - Daily ingestion of green tea catechins from adulthood suppressed brain
      dysfunction in aged mice.
AB  - Oxidative damage is believed to be an important cause of senescence. We have
      previously found that green tea catechins (GT-catechin), potent antioxidants,
      decrease oxidative damage to DNA and suppress brain dysfunction in aged
      senescence-accelerated mice (SAMP10) when ingested from the age of 1 month to the
      age of 12 months. To clarify the effect of GT-catechin on suppression of brain
      senescence, we investigated the effect of starting period to ingest GT-catechin.
      Six- or 9-month-old SAMP10 mice were allowed free access to water containing
      0.02% GT-catechin. SAMP10 mice exhibit senescence characteristics such as
      shortened life span, atrophied forebrain and lowered learning and memory
      abilities. Learning ability was significantly higher in mice that ingested GT
      catechin from the age of 6 months to 12 months when compared with same-aged
      control mice drank water without GT-catechin. Starting GT-catechin intake from
      the age of 9 months tended to improve learning ability. The ages of 6 and 9
      months are thought to be adult and middle ages, respectively in SAMP10 mice. This
      result suggested that GT-catechin was helpful in suppressing brain dysfunction
      with aging even when ingestion started at the adult age.

PMID- 19850982
TI  - Folate deficiency followed by ionizing radiation perturbs hepatic dihydrofolate
      reducatse activity.
AB  - There is lot of interest in the folate metabolism because of the essential role
      of folate coenzymes in nucleic acid synthesis. Gamma (gamma) radiation is well
      known for inducing damage in the DNA. To counteract these damage, a variety of
      DNA repair pathways have evolved that require regular supply of DNA bases whose
      biosynthesis in turn depends on sufficient pools of folate dependent enzymes like
      dihydrofolate reductase (DHFR). In the present study, we examined the ionizing
      radiation mediated perturbation of DHFR activity in folate deficient and folate
      sufficient conditions. In folate deficient animals a potent inhibition of liver
      DHFR activity was observed. Our results showed that combination of folate
      starvation and ionizing radiation might adversely affect the DHFR activity,
      compared to their individual treatments. Measurement of apurinic/apyrimidinic
      sites (AP sites), a major type of DNA damage generated by radiation induced loss
      of purine and/or pyrimidine base, indicated a dose dependent DNA damage in folate
      deficient animals. In conclusion our data suggest an interactive role of folate
      deficiency and radiation injury in inhibiting DHFR activity.

PMID- 19850983
TI  - The effect of biothiol on UV irradiated alpha-lipoic acid.
AB  - alpha-Lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) are well
      known as strong antioxidants. LA has the characteristic distorted five membered
      1,2-dithiolane ring, which is quite vulnerable to UV irradiation. The UV induced
      decomposition of LA and the effect of the following addition of biothiols to the
      photoirradiated solution of LA were investigated by UV-vis spectrometry and (1)H
      NMR spectral analysis. The mechanism of UV irradiated LA decomposition was
      proposed based on the results obtained from NMR and GPC measurements.

PMID- 19850984
TI  - Inhibitory effects of caffeine and its metabolites on intracellular lipid
      accumulation in murine 3T3-L1 adipocytes.
AB  - To understand the mechanisms of the anti-obesity effects of dietary caffeine, the
      effects of caffeine and its metabolites on adipocyte differentiation and insulin
      stimulated glucose uptake in murine 3T3-L1 adipocytes were investigated. Caffeine
      did not inhibit the differentiation of 3T3-L1 pre-adipocytes to mature
      adipocytes, but it did suppress the intracellular lipid accumulation after
      complete differentiation in a dose-dependent manner (0.125-1.0 mM). This effect
      was also observed in 1,3,7-trimethyluric acid- 3,7-dimethyluric acid- and 5
      acetylamino-6-formylamino-3-methyluracil-treated cells. Caffeine also inhibited
      insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes in a dose
      dependent manner. Treatment with theophylline, paraxanthine, 1-methylxanthine
      (MX), 3-MX, or 7-MX also inhibited glucose uptake in differentiated adipocytes.
      These results suggest that the anti-obesity activity of dietary caffeine is due
      to the additive and/or synergistic inhibitory effects of caffeine and its
      metabolites on intracellular lipid accumulation and that caffeine does not affect
      adipocyte differentiation.

PMID- 19850985
TI  - Modulation of energy metabolic enzyme expression in N-nitrosodiethylamine
      mediated hepatocarcinogenesis by Chinese herbs, Huqi San.
AB  - AIM: To elucidate the anticancer mechanism of Huqi San by assessing the
      expression of G-6-Pase, SDH, ATPase and AFP in N-nitrosodiethylamine-mediated
      hepatocarcinogenesis in rats. METHODS: A Solt-Farber two-step test model of
      hepatocarcino genesis was established by diethylnitrosamine (DEN) and 2
      acetylaminofluorene (AAF) in rats to investigate the modifying effects of
      expression of 6-glucosephosphatase (G-6-Pase), succinodehydrogenase (SDH),
      adenosine triphosphatase (ATPase) in N-nitrosodiethylamine-mediated
      hepatocarcinogenesis. Hu Qisan compounded by eight medicinal herbs was prepared
      in glycoprival granules with wich 0.38 g crude herbs/mL solution was prepared for
      administration. gamma-Glutamy-transpeptidase (gamma-GT), G-6-Pase, SDH and ATPase
      were immunohistochemically determined. The activity of alpha-fetoglobulin (AFP)
      in the livers was measured with Immunofluorescence. RESULTS: Huqi San treated
      rats showed significant decrease in areas of gamma-GT positive foci (P< 0.001).
      On the other hand, the expression of G-6-Pase, SDH and ATPase has obviously
      altered in Huqi San treated group. The activity of AFP also significantly
      decreased after the treatment with Huqi San (8 g/kg body weight or 4 g/kg body
      weight) or total alkali of mistletoe (0.12 g/kg body weight). CONCLUSIONS: Huqi
      San can obviously increase these activities of G-6-Pase, SDH and ATPase, and at
      the same time significantly decrease the expression of gamma-GT and AFP.
      Therefore, it can obstruct or inhibit the rat's liver preneolastic lesion induced
      by DEN.

PMID- 19850986
TI  - Radicicol-mediated inhibition of Bcr-Abl in K562 cells induced p38-MAPK dependent
      erythroid differentiation and PU.1 down-regulation.
AB  - Constitutive tyrosine kinase activity of the breakpoint cluster region (Bcr)-Abl
      fusion protein is characteristic of chronic myelogenous leukemia (CML). As
      resistance against Imatinib a Bcr-abl inhibitor used in CML, was described, Heat
      shock protein (Hsp90) became an alternative target as inhibition of Bcr-Abl-Hsp90
      complex leads to proliferation arrest. Here, we used natural product Radicicol
      (Rad), a macrocyclic antifungal, as an Hsp90 inhibitor to investigate the effect
      of Bcr-Abl inactivation on erythroid gene expression and subsequently on the
      transcription factors involved in their regulation. We showed that all erythroid
      genes studied were over-expressed after Rad treatment while Bcr-Abl expression
      was inhibited. Specific transcription factor NF-E2 was induced in Rad-treated
      cells as well as GATA-1 cofactors Friend of GATA (FOG)1 and SP1, whereas PU.1 was
      downregulated. Moreover, p38 mitogen activated protein kinase (MAPK) inhibition
      prevented Rad-mediated differentiation of K562 in correlation with decreased
      gamma-globin expression and suppression of Rad-mediated inhibition of PU.1. In
      conclusion, our results show that Radicicol leads to Bcr-Abl inactivation via
      Hsp90 inhibition inducing reactivation of the erythroid program in K562 cells.

PMID- 19850987
TI  - Long-term schisandrin B treatment mitigates age-related impairments in
      mitochondrial antioxidant status and functional ability in various tissues, and
      improves the survival of aging C57BL/6J mice.
AB  - Mitochondrial decay is a major cause of aging, leading to the subsequent death of
      aerobic organisms including humans. In the present study, we examined the effects
      of supplementation with schisandrin B (Sch B, a dibenzocyclooctadiene derivative
      isolated from the fruit of Schisandra chinensis), administered at 0.012% (w/w) of
      diet, starting from the age of 36 weeks, on age-dependent changes in mouse
      mitochondrial antioxidant status and functional ability in various tissues
      (brain, heart, liver, and kidney) up to the age of 120 weeks. We also monitored
      survival of male and female C57BL/6J mice. Aging caused progressive impairment in
      mitochondrial antioxidant status in various tissues, as evidenced by decreases in
      reduced glutathione and alpha-tocopherol levels, and Mn-superoxide dismutase
      activity. Impairments in mitochondrial antioxidant status were invariably
      associated with increases in mitochondria-driven reactive oxygen species (ROS)
      production in tissue homogenates, as well as decreased mitochondrial ATP
      generation capacities (ATP-GCs), in all tested tissues. Diet supplementation with
      Sch B ameliorated impairment in mitochondrial antioxidant status during aging.
      The effects were more pronounced in younger than in older mice, when compared to
      age-matched non-supplemented controls. Sch B supplementation also suppressed
      mitochondria-driven ROS production and enhanced mitochondrial ATP-GC in various
      tissues during aging. The beneficial effects of Sch B supplementation on
      mitochondrial antioxidant status and functional ability were paralleled by
      survival improvement in aging male mice, when compared with controls. Sch B
      supplementation also improved the survival in female mice. In conclusion, long
      term Sch B supplementation mitigated age-dependent impairments in mitochondrial
      antioxidant capacity and functional ability, thereby retarding the aging process
      in mice, particularly during early aging.

PMID- 19850988
TI  - Clinical aspects of invasive lobular breast carcinoma (ILBC).

PMID- 19850989
TI  - Hormone replacement therapy and the increase in the incidence of invasive lobular
      cancer.
AB  - Individual epidemiologic studies and a meta-analysis of those studies suggest
      that the relative risk of invasive lobular and compared to invasive ductal cancer
      is particularly affected by combined hormone replacement therapy (HRT) in
      postmenopausal women, with an approximate doubling of risk of invasive lobular
      breast cancer in current users. However, this was not seen in the Women's Health
      Initiative trial comparing combined HRT and placebo, although this trial had only
      modest statistical power to demonstrate the effect. In the absence of some
      obvious source of bias (screening mammography rates were well balanced between
      HRT users and non-users in most studies), this evidence supports the hypothesis
      that combined HRT increases the risk of lobular breast cancer.

PMID- 19850990
TI  - Molecular pathology of invasive lobular breast carcinoma.

PMID- 19850991
TI  - Histology and immunophenotype of invasive lobular breast cancer. daily practice
      and pitfalls.
AB  - Invasive lobular carcinomas (ILC) represent the most common subtype of invasive
      breast cancer and account for about 5-15% of all breast cancer cases. Invasive
      lobular carcinoma is often accompanied by in situ lesions, by lobular neoplasia
      (LN). Invasive lobular carcinomas display diverse histologic patterns varying
      from classical through solid to pleomorphic subtypes. When analyzing histological
      subtypes, the classical variant is reported to have a more favorable outcome. The
      majority of invasive lobular carcinomas are hormone receptor positive,
      overexpression and/or amplification of the Her2 gene is lower than in carcinomas
      of invasive ductal type. Loss of heterozygosity of the 16q chromosomal regions
      and the consequent lack of E-Cadherin expression are common findings in invasive
      lobular carcinomas. Intra-operative evaluation of resection margins in ILC is
      often unsatisfactory due to the diffuse nature of the tumor. Size estimation of
      the invasive component poses a similar challenge in daily practice.

PMID- 19850992
TI  - Mammography, sonography and MRI for detection and characterization of invasive
      lobular carcinoma of the breast.
AB  - Imaging of invasive lobular carcinoma (ILC) is more challenging than other types
      of breast cancer because of its spider web like growth pattern. Mammography has a
      relevant number of false negative exams, especially in dense breasts.
      Mammographic appearance of ILC is often subtle. Distinct mass like aspects are
      absent more often when compared with other types of breast cancer, and lesions
      are frequently only mildly opaque. Microcalcifications are uncommon. The addition
      of an ultrasound exam can improve rates of detection and diagnosis of ILC, but
      even when combining modalities ILC can be missed. If clinical signs are
      suspicious, magnetic resonance imaging (MRI) can help to detect ILC. MRI should
      also be considered in preoperative staging if treatment with breast conservation
      is favoured, particularly to assess maximal tumor dimensions. Mammographic
      findings do not correlate well with pathological tumor size. Additional tumor
      sites detected by MRI only should be validated cautiously, and guidelines
      established for multicentricity detected by mammography should not be used in the
      same way.

PMID- 19850993
TI  - Clinical presentation and surgical management of invasive lobular carcinoma of
      the breast.
AB  - Invasive lobular carcinoma is the second most common histological type of breast
      cancer and differs from invasive ductal carcinoma also in some clinical features.
      Multifocal or multicentric as well as contralateral diseases are more frequently
      found among patients with lobular carcinoma. Tumor size at diagnosis is larger
      than in patients with ductal carcinoma due to diagnostic challenges associated
      with lobular histology. For surgical management, breast conserving surgery
      followed by radiotherapy offers equal local control as mastectomy. Controversy
      however exists regarding risk for positive margins and subsequent need for second
      operations. Axillary staging can be safely performed by sentinel node biopsy if
      lymph nodes are clinically negative, even in multifocal or multicentric disease.

PMID- 19850994
TI  - Distinct clinical and prognostic features of invasive lobular breast cancer.

PMID- 19850995
TI  - Infiltrating lobular carcinoma of the breast: systemic treatment.
AB  - Invasive lobular carcinoma (ILC) is the second most common type of breast cancer
      after invasive ductal carcinoma (IDC). It is characterized by unique clinical,
      biological and molecular properties. ILC is almost always positive for the
      estrogen receptor and is typically of a lower grade compared with IDC. We have
      reviewed selected literature on preoperative (neoadjuvant) and adjuvant systemic
      therapy of breast cancer focusing on the differential therapy of ILC. Despite the
      importance of this type of breast cancer, information about its specific
      treatment is sparse, in particular with regard to adjuvant systemic chemotherapy.
      ILC has significantly lower rates of response to neoadjuvant chemotherapy
      compared with IDC; however, the low chemosensitivity seems not to result in a
      survival disadvantage. Adjuvant hormonal therapy studies do not distinguish
      between ILC and IDC. Thus, recommendations about endocrine therapies are made
      using the same criteria as for IDC.

PMID- 19850996
TI  - Relapse of invasive lobular carcinoma.

PMID- 19850997
TI  - Infiltrating lobular carcinoma: four case illustrations.

PMID- 19850998
TI  - Laboratory communications in Acta Crystallographica Section F.

PMID- 19850999
TI  - Structures of two truncated phage-tail hyaluronate lyases from Streptococcus
      pyogenes serotype M1.
AB  - The crystal structures of truncated forms of the Streptococcus pyogenes phage
      encoded hyaluronate lyases HylP2 and HylP3 were determined by molecular
      replacement to 1.6 and 1.9 A resolution, respectively. The truncated forms
      crystallized in a hexagonal space group, forming a trimer around the threefold
      crystallographic axis. The arrangement of the fold is very similar to that
      observed in the structure of the related hyaluronate lyase HylP1. The structural
      elements putatively involved in substrate recognition are found to be conserved
      in both the HylP2 and HylP3 fragments.

PMID- 19851000
TI  - Use of thallium to identify monovalent cation binding sites in GroEL.
AB  - GroEL is a bacterial chaperone protein that assembles into a homotetradecameric
      complex exhibiting D(7) symmetry and utilizes the co-chaperone protein GroES and
      ATP hydrolysis to assist in the proper folding of a variety of cytosolic
      proteins. GroEL utilizes two metal cofactors, Mg(2+) and K(+), to bind and
      hydrolyze ATP. A K(+)-binding site has been proposed to be located next to the
      nucleotide-binding site, but the available structural data do not firmly support
      this conclusion. Moreover, more than one functionally significant K(+)-binding
      site may exist within GroEL. Because K(+) has important and complex effects on
      GroEL activity and is involved in both positive (intra-ring) and negative (inter
      ring) cooperativity for ATP hydrolysis, it is important to determine the exact
      location of these cation-binding site(s) within GroEL. In this study, the K(+)
      mimetic Tl(+) was incorporated into GroEL crystals, a moderately redundant 3.94 A
      resolution X-ray diffraction data set was collected from a single crystal and the
      strong anomalous scattering signal from the thallium ion was used to identify
      monovalent cation-binding sites. The results confirmed the previously proposed
      placement of K(+) next to the nucleotide-binding site and also identified
      additional binding sites that may be important for GroEL function and
      cooperativity. These findings also demonstrate the general usefulness of Tl(+)
      for the identification of monovalent cation-binding sites in protein crystal
      structures, even when the quality and resolution of the diffraction data are
      relatively low.

PMID- 19851001
TI  - Structure of Mycobacterium tuberculosis Rv2714, a representative of a duplicated
      gene family in Actinobacteria.
AB  - The gene Rv2714 from Mycobacterium tuberculosis, which codes for a hypothetical
      protein of unknown function, is a representative member of a gene family that is
      largely confined to the order Actinomycetales of Actinobacteria. Sequence
      analysis indicates the presence of two paralogous genes in most mycobacterial
      genomes and suggests that gene duplication was an ancient event in bacterial
      evolution. The crystal structure of Rv2714 has been determined at 2.6 A
      resolution, revealing a trimer in which the topology of the protomer core is
      similar to that observed in a functionally diverse set of enzymes, including
      purine nucleoside phosphorylases, some carboxypeptidases, bacterial peptidyl-tRNA
      hydrolases and even the plastidic form of an intron splicing factor. However,
      some structural elements, such as a beta-hairpin insertion involved in protein
      oligomerization and a C-terminal alpha-helical domain that serves as a lid to the
      putative substrate-binding (or ligand-binding) site, are only found in Rv2714
      bacterial homologues and represent specific signatures of this protein family.

PMID- 19851002
TI  - New structural insights and molecular-modelling studies of 4-methyl-5-beta
      hydroxyethylthiazole kinase from Pyrococcus horikoshii OT3 (PhThiK).
AB  - 4-Methyl-5-beta-hydroxyethylthiazole kinase (ThiK) catalyses the phosphorylation
      of the hydroxyl group of 4-methyl-5-beta-hydroxyethylthiazole. This work reports
      the first crystal structure of an archaeal ThiK: that from Pyrococcus horikoshii
      OT3 (PhThiK) at 1.85 A resolution with a phosphate ion occupying the position of
      the beta-phosphate of the nucleotide. The topology of this enzyme shows the
      typical ribokinase fold of an alpha/beta protein. The overall structure of PhThiK
      is similar to those of Bacillus subtilis ThiK (BsThiK) and Enterococcus faecalis
      V583 ThiK (EfThiK). Sequence analysis of ThiK enzymes from various sources
      indicated that three-quarters of the residues involved in interfacial regions are
      conserved. It also revealed that the amino-acid residues in the nucleotide
      binding, magnesium ion-binding and substrate-binding sites are conserved. Binding
      of the nucleotide and substrate to the ThiK enzyme do not influence the
      quaternary association (trimer) as revealed by the crystal structure of PhThiK.

PMID- 19851003
TI  - The structure of Staphylococcus aureus phosphopantetheine adenylyltransferase in
      complex with 3'-phosphoadenosine 5'-phosphosulfate reveals a new ligand-binding
      mode.
AB  - Bacterial phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate
      step in the coenzyme A (CoA) biosynthetic pathway. It catalyzes the reversible
      transfer of an adenylyl group from ATP to 4'-phosphopantetheine (Ppant) to form
      dephospho-CoA (dPCoA) and pyrophosphate. Previous structural studies have
      revealed how several ligands are recognized by bacterial PPATs. ATP, ADP, Ppant
      and dPCoA bind to the same binding site in a highly similar manner, while CoA
      binds to a partially overlapping site in a different mode. To provide further
      structural insights into ligand binding, the crystal structure of Staphylococcus
      aureus PPAT was solved in a binary complex with 3'-phosphoadenosine 5'
      phosphosulfate (PAPS). This study unexpectedly revealed a new mode of ligand
      binding to PPAT, thus providing potentially useful information for structure
      based discovery of inhibitors of bacterial PPATs.

PMID- 19851004
TI  - High-resolution structure of human carbonic anhydrase II complexed with
      acetazolamide reveals insights into inhibitor drug design.
AB  - The crystal structure of human carbonic anhydrase II (CA II) complexed with the
      inhibitor acetazolamide (AZM) has been determined at 1.1 A resolution and refined
      to an R(cryst) of 11.2% and an R(free) of 14.7%. As observed in previous CA II
      inhibitor complexes, AZM binds directly to the zinc and makes several key
      interactions with active-site residues. The high-resolution data also showed a
      glycerol molecule adjacent to the AZM in the active site and two additional AZMs
      that are adventitiously bound on the surface of the enzyme. The co-binding of AZM
      and glycerol in the active site demonstrate that given an appropriate ring
      orientation and substituents, an isozyme-specific CA inhibitor may be developed.

PMID- 19851005
TI  - Expression, purification and preliminary X-ray analysis of the Neisseria
      meningitidis outer membrane protein PorB.
AB  - The Neisseria meningitidis outer membrane protein PorB was expressed in
      Escherichia coli and purified from inclusion bodies by denaturation in urea
      followed by refolding in buffered LDAO on a size-exclusion column. PorB has been
      crystallized in three different crystal forms: C222, R32 and P6(3). The C222
      crystal form may contain either one or two PorB monomers in the asymmetric unit,
      while both the R32 and P6(3) crystal forms contained one PorB monomer in the
      asymmetric unit. Of the three, the P6(3) crystal form had the best diffraction
      quality, yielding data extending to 2.3 A resolution.

PMID- 19851006
TI  - Purification and crystallization of a putative transcriptional regulator of the
      benzoate oxidation pathway in Burkholderia xenovorans LB400.
AB  - Burkholderia xenovorans LB400 harbours two paralogous copies of the recently
      discovered benzoate oxidation (box) pathway. While both copies are functional,
      the paralogues are differentially regulated and flanked by putative
      transcriptional regulators from distinct families. The putative LysR-type
      transcriptional regulator (LTTR) adjacent to the megaplasmid-encoded box enzymes,
      Bxe_C0898, has been produced recombinantly in Escherichia coli and purified to
      homogeneity. Gel-filtration studies show that Bxe_C0898 is a tetramer in
      solution, consistent with previously characterized LTTRs. Bxe_C0898 crystallized
      with four molecules in the asymmetric unit of the P4(3)2(1)2/P4(1)2(1)2 unit cell
      with a solvent content of 61.19%, as indicated by processing of the X-ray
      diffraction data. DNA-protection assays are currently under way in order to
      identify potential operator regions for this LTTR and to define its role in
      regulation of the box pathway.

PMID- 19851007
TI  - Expression, purification, crystallization and preliminary X-ray analysis of para
      nitrophenol 4-monooxygenase from Pseudomonas putida DLL-E4.
AB  - Para-nitrophenol 4-monooxygenase (PnpA) plays an important role in bacterial
      degradation of para-nitrophenol by oxidative release of the nitro group from the
      aromatic ring to form p-benzoquinone. In order to understand the structural basis
      of the function of this enzyme, PnpA was cloned, expressed in Escherichia coli
      and purified. PnpA was crystallized by the hanging-drop vapour-diffusion
      technique with PEG 4000 as precipitant. The PnpA crystals belonged to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 54.47, b = 77.56, c = 209.17 A, and
      diffracted to 2.24 A resolution.

PMID- 19851008
TI  - Crystallization and heavy-atom derivatization of StHsp14.0, a small heat-shock
      protein from Sulfolobus tokodaii.
AB  - Small heat-shock proteins (sHsps) bind and stabilize proteins denatured by heat
      or other stresses in order to prevent unfavourable protein aggregation. StHsp14.0
      is an sHsp found in the acidothermophilic archaeon Sulfolobus tokodaii. A variant
      of StHsp14.0 was crystallized by the sitting-drop vapour-diffusion method. The
      crystals diffracted X-rays to 1.85 A resolution and belonged to space group
      P2(1)2(1)2, with unit-cell parameters a = 40.4, b = 61.1, c = 96.1 A. The V(M)
      value was estimated to be 2.1 A(3) Da(-1), assuming the presence of two molecules
      in the asymmetric unit. Heavy-atom derivative crystals were prepared successfully
      by the cocrystallization method and are isomorphic to native crystals.

PMID- 19851009
TI  - Crystallization and preliminary X-ray diffraction analysis of crotoxin B from
      Crotalus durissus collilineatus venom.
AB  - Crotoxin B is a basic phospholipase A(2) found in the venom of several Crotalus
      durissus ssp. rattlesnakes and is one of the subunits that constitute crotoxin,
      the main component of the venom of these snakes. This heterodimeric toxin is
      related to important envenomation effects such as neurological disorders,
      myotoxicity and renal failure. Although crotoxin was first crystallized in 1938,
      the first structural data only became available in 2007 (for crotoxin B from C.
      durissus terrificus) and showed an ambiguous result for the biological assembly,
      which could be either dimeric or tetrameric. In this work, the crystallization, X
      ray diffraction data collection at 2.2 A resolution and molecular-replacement
      solution of a dimeric complex formed by two crotoxin B isoforms from C. durissus
      collilineatus venom is presented.

PMID- 19851010
TI  - Crystallization and preliminary X-ray analysis of mannosyl-3-phosphoglycerate
      synthase from Thermus thermophilus HB27.
AB  - Mannosylglycerate (MG) is a compatible solute that is widespread in marine
      organisms that are adapted to hot environments, with its intracellular pool
      generally increasing in response to osmotic stress. These observations suggest
      that MG plays a relevant role in osmoadaptation and thermoadaptation. The
      pathways for the synthesis of MG have been characterized in a number of
      thermophilic and hyperthermophilic organisms. Mannosyl-3-phosphoglycerate
      synthase (MpgS) is a key enzyme in the biosynthesis of MG. Here, the
      purification, crystallization and preliminary crystallographic characterization
      of apo MpgS from Thermus thermophilus HB27 are reported. The addition of Zn(2+)
      to the crystallization buffer was essential in order to obtain crystals. The
      crystals belonged to one of the enantiomorphic tetragonal space groups P4(1)2(1)2
      or P4(3)2(1)2, with unit-cell parameters a = b = 113, c = 197 A. Diffraction data
      were obtained to a resolution of 2.97 A.

PMID- 19851011
TI  - Crystallization and preliminary X-ray analysis of ZHE1, a hatching enzyme from
      the zebrafish Danio rerio.
AB  - The hatching enzyme of the zebrafish, ZHE1 (29.3 kDa), is a zinc metalloprotease
      that catalyzes digestion of the egg envelope (chorion). ZHE1 was heterologously
      expressed in Escherichia coli, purified and crystallized by the hanging-drop
      vapour-diffusion method using PEG 3350 as the precipitant. Two diffraction data
      sets with resolution ranges 50.0-1.80 and 50.0-1.14 A were independently
      collected from two crystals and were merged to give a highly complete data set
      over the full resolution range 50.0-1.14 A. The space group was assigned as
      primitive orthorhombic P2(1)2(1)2(1), with unit-cell parameters a = 32.9, b =
      62.5, c = 87.4 A. The crystal contained one ZHE1 molecule in the asymmetric unit.

PMID- 19851012
TI  - Crystallization and preliminary X-ray diffraction characterization of RpfF, a key
      DSF synthase from Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia has emerged as a critical nosocomial opportunistic
      pathogen in the last few years. It is resistant to many clinically useful
      antibiotics; hence, new ways of combatting this bacterium are essential.
      Diffusible signal factor (DSF) dependent quorum sensing is a major mechanism of
      virulence induction in S. maltophilia, with RpfF playing a key role in DSF
      biosynthesis. Inhibiting S. maltophilia RpfF (SmRpfF) function via small-molecule
      interference may constitute a new way of treating S. maltophilia infection.
      SmRpfF was therefore overexpressed in Escherichia coli, purified and crystallized
      using the hanging-drop vapour-diffusion method. The crystals belonged to the
      tetragonal space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b
      = 148.51, c = 122.82 A, and diffracted to a resolution of 2.25 A.

PMID- 19851013
TI  - Crystallization and preliminary X-ray analysis of a D-Ala:D-Ser ligase associated
      with VanG-type vancomycin resistance.
AB  - Acquired VanG-type resistance to vancomycin in Enterococcus faecalis BM4518
      arises from inducible synthesis of peptidoglycan precursors ending in D-alanyl-D
      serine, to which vancomycin exhibits low binding affinity. VanG, a D-alanine:D
      serine ligase, catalyzes the ATP-dependent synthesis of the D-Ala-D-Ser
      dipeptide, which is incorporated into the peptidoglycan synthesis of VanG-type
      vancomycin-resistant strains. Here, the purification, crystallization and
      preliminary crystallographic analysis of VanG in complex with ADP are reported.
      The crystal belonged to space group P3(1)21, with unit-cell parameters a = b =
      116.1, c = 177.2 A, and contained two molecules in the asymmetric unit. A
      complete data set has been collected to 2.35 A resolution from a single crystal
      under cryogenic conditions using synchrotron radiation.

PMID- 19851014
TI  - Purification, crystallization and preliminary X-ray diffraction studies of
      parakeet (Psittacula krameri) haemoglobin.
AB  - Birds often show efficient oxygen management in order to meet the special demands
      of their metabolism. However, the structural studies of avian haemoglobins (Hbs)
      are inadequate for complete understanding of the mechanism involved. Towards this
      end, purification, crystallization and preliminary X-ray diffraction studies have
      been carried out for parakeet Hb. Parakeet Hb was crystallized as the met form in
      low-salt buffered conditions after extracting haemoglobin from crude blood by
      microcentrifugation and purifying the sample by column chromatography. Good
      quality crystals were grown from 10% PEG 3350 and a crystal diffracted to about
      2.8 A resolution. Preliminary diffraction data showed that the Hb crystal
      belonged to the monoclinic system (space group C2), with unit-cell parameters a =
      110.68, b = 64.27, c = 56.40 A, beta = 109.35 degrees . Matthews volume analysis
      indicated that the crystals contained a half-tetramer in the asymmetric unit.

PMID- 19851015
TI  - Crystallization and crystal-packing studies of Chlorella virus deoxyuridine
      triphosphatase.
AB  - The 141-amino-acid deoxyuridine triphosphatase (dUTPase) from the algal Chlorella
      virus IL-3A and its Glu81Ser/Thr84Arg-mutant derivative Mu-22 were crystallized
      using the hanging-drop vapor-diffusion method at 298 K with polyethylene glycol
      as the precipitant. An apo IL-3A dUTPase with an amino-terminal T7 epitope tag
      and a carboxy-terminal histidine tag yielded cubic P2(1)3 crystals with unit-cell
      parameter a = 106.65 A. In the presence of dUDP, the enzyme produced thin stacked
      orthorhombic P222 crystals with unit-cell parameters a = 81.0, b = 96.2, c =
      132.8 A. T7-histidine-tagged Mu-22 dUTPase formed thin stacked rectangular
      crystals. Amino-terminal histidine-tagged dUTPases did not crystallize but formed
      aggregates. Glycyl-seryl-tagged dUTPases yielded cubic P2(1)3 IL-3A crystals with
      unit-cell parameter a = 105.68 A and hexagonal P6(3) Mu-22 crystals with unit
      cell parameters a = 132.07, c = 53.45 A, gamma = 120 degrees . Owing to the
      Thr84Arg mutation, Mu-22 dUTPase had different monomer-to-monomer interactions to
      those of IL-3A dUTPase.

PMID- 19851016
TI  - Expression, purification and preliminary crystallographic analysis of Pseudomonas
      aeruginosa RocR protein.
AB  - Pseudomonas aeruginosa RocR, an EAL-domain protein which regulates the expression
      of virulence genes and biofilm formation, has been cloned and expressed in
      Escherichia coli and purified. Here, the crystallization and preliminary
      diffraction analysis of RocR are reported. The X-ray diffraction data were
      processed to a resolution of 2.50 A. The crystals belonged to space group P6(1)22
      or P6(5)22, with unit-cell parameters a = 118.8, b = 118.8, c = 495.1 A, alpha =
      beta = 90, gamma = 120 degrees .

PMID- 19851017
TI  - Crystallization and preliminary X-ray crystallographic studies of O
      methyltransferase from Anabaena PCC 7120.
AB  - O-Methyltransferase (OMT) is a ubiquitous enzyme that exists in bacteria, plants
      and humans and catalyzes a methyl-transfer reaction using S-adenosyl-L-methionine
      as a methyl donor and a wide range of phenolics as acceptors. To investigate the
      structure and function of OMTs, omt from Anabaena PCC 7120 was cloned into
      expression vector pET21a and expressed in a soluble form in Escherichia coli
      strain BL21 (DE3). The recombinant OMT protein was purified to homogeneity using
      a two-step strategy. Crystals of OMT that diffracted to a resolution of 2.4 A
      were obtained using the hanging-drop vapour-diffusion method. The crystals
      belonged to space group C222(1), with unit-cell parameters a = 131.620, b =
      227.994, c = 150.777 A, alpha = beta = gamma = 90 degrees . There are eight
      molecules per asymmetric unit.

PMID- 19851018
TI  - Towards the structure of the C-terminal part of the S-layer protein SbsC.
AB  - The S-layer protein SbsC from Geobacillus stearothermophilus ATCC 12980 is the
      most prevalent single protein produced by the bacterium and covers the complete
      bacterial surface in the form of a two-dimensional crystalline monolayer. In
      order to elucidate the structural features of the assembly domains, several N
      terminally truncated fragments of SbsC have been crystallized. Crystals obtained
      from recombinant fragments showed anisotropic diffraction to a maximum of 3.5 A
      resolution using synchrotron radiation. The best diffracting crystals were
      obtained from rSbsC(755-1099), an unintentional in situ proteolytic degradation
      product of rSbsC(447-1099). Crystals were obtained in two different space groups,
      P2(1) and P4(1)2(1)2, and diffracted to 2.6 and 3 A resolution, respectively.
      Native and heavy-atom derivative data have been collected. The structure of the C
      terminal part will yield atomic resolution information for the domains that are
      crucial for the assembly of the two-dimensional lattice.

PMID- 19851020
TI  - Preliminary X-ray crystallographic analysis of a nitric oxide-inducible lactate
      dehydrogenase from Staphylococcus aureus.
AB  - Recent studies have indicated that Staphylococcus aureus can survive the
      nitrosative stress (caused by the radical nitric oxide; NO.) mounted by the
      immune system of the infected host. It does this by expressing a nitric oxide
      inducible L-lactate dehydrogenase (Sa-LDH-1). Therefore, if efficient inhibitors
      of Sa-LDH-1 can be designed then Sa-LDH-1 could be a potential drug target
      against the pathogen S. aureus. For this purpose, the nitric acid-inducible LDH-1
      from S. aureus COL strain has been cloned into the expression vector pET-28a(+)
      and the protein has been expressed, purified and crystallized. The Sa-LDH-1
      crystal diffracted to 2.4 A resolution at a home X-ray source and belonged to
      space group C2, with unit-cell parameters a = 131.4, b = 74.4, c = 103.2 A, beta
      = 133.4 degrees .

PMID- 19851019
TI  - A novel noncovalent complex of chorismate mutase and DAHP synthase from
      Mycobacterium tuberculosis: protein purification, crystallization and X-ray
      diffraction analysis.
AB  - Chorismate mutase catalyzes a key step in the shikimate-biosynthetic pathway and
      hence is an essential enzyme in bacteria, plants and fungi. Mycobacterium
      tuberculosis contains two chorismate mutases, a secreted and an intracellular
      one, the latter of which (MtCM; Rv0948c; 90 amino-acid residues; 10 kDa) is the
      subject of this work. Here are reported the gene expression, purification and
      crystallization of MtCM alone and of its complex with another shikimate-pathway
      enzyme, DAHP synthase (MtDS; Rv2178c; 472 amino-acid residues; 52 kDa), which has
      been shown to enhance the catalytic efficiency of MtCM. The MtCM-MtDS complex
      represents the first noncovalent enzyme complex from the common shikimate pathway
      to be structurally characterized. Soaking experiments with a transition-state
      analogue are also reported. The crystals of MtCM and the MtCM-MtDS complex
      diffracted to 1.6 and 2.1 A resolution, respectively.

PMID- 19851021
TI  - Crystallization and preliminary X-ray diffraction characterization of an
      essential protein from Xanthomonas campestris that contains a noncanonical PilZ
      signature motif yet is critical for pathogenicity.
AB  - Recent studies have identified c-di-GMP as a novel secondary messenger molecule
      that is heavily involved in regulating bacterial biofilm formation, motility,
      production of pathogenicity factors etc. PilZ domain-containing proteins have
      been suggested and subsequently proved to be the c-di-GMP receptor. However,
      considering the diverse biological functions exhibited by c-di-GMP, it may be
      that receptors other than the PilZ domain exist. An essential protein from the
      plant pathogen Xanthomonas campestris pv. campestris (Xcc) that contains a
      noncanonical PilZ signature motif yet is critical for Xcc pathogenicity has been
      cloned, purified and crystallized. Detailed characterization of this protein may
      reveal an alternative binding mode of c-di-GMP and allow a more thorough
      understanding of how c-di-GMP exhibits its diverse effects.

PMID- 19851022
TI  - Crystallization and preliminary X-ray diffraction analysis of the middle domain
      of Paip1.
AB  - The poly(A)-binding protein (PABP) simultaneously interacts with the poly(A) tail
      of mRNAs and the scaffolding protein eIF4G to mediate mRNA circularization,
      resulting in stimulation of protein translation. PABP is regulated by the PABP
      interacting protein Paip1. Paip1 is thought to act as a translational activator
      in 5' cap-dependent translation by interacting with PABP and the initiation
      factors eIF4A and eIF3. Here, the crystallization and preliminary diffraction
      analysis of the middle domain of Paip1 (Paip1M), which produces crystals that
      diffract to a resolution of 2.2 A, are presented.

PMID- 19851023
TI  - Cloning, purification and preliminary X-ray crystallographic analysis of a
      hypothetical protein, MJ0754, from Methanococcus jannaschii DSM 2661.
AB  - The protein encoded by the MJ0754 gene from the archaeon Methanococcus jannaschii
      DSM 2661 is an unknown hypothetical protein. Two recombinant proteins, MJ0754
      (residues 1-185) and MJ0754t (a truncated form of MJ0754, residues 11-185), were
      cloned from MJ0754, overexpressed as His-tag fusion proteins and purified. The
      crystals were found to grow under two different conditions and to have two
      different shapes. The crystal of MJ0754 belonged to space group P6(1), with unit
      cell parameters a = b = 127.015, c = 48.929 A, a calculated Matthews coefficient
      of 2.85 A(3) Da(-1) and two molecules per asymmetric unit. The crystal of MJ0754t
      belonged to space group C222(1), with unit-cell parameters a = 51.915, b =
      79.122, c = 93.869 A, a calculated Matthews coefficient of 2.41 A(3) Da(-1) and
      one molecule per asymmetric unit. The SeMet-labelled P6(1) crystal diffracted to
      a resolution of 3.1 A, while the native C222(1) crystal diffracted to 1.3 A
      resolution.

PMID- 19851024
TI  - How to get the magic triangle and the MAD triangle into your protein crystal.
AB  - The magic triangle 5-amino-2,4,6-triiodoisophthalic acid (I3C) and the MAD
      triangle 5-amino-2,4,6-tribromoisophthalic acid (B3C) are two representatives of
      a novel class of compounds that combine heavy atoms for experimental phasing with
      functional groups for protein interactions. These compounds are readily available
      and provide easy access to experimental phasing. The preparation of stock
      solutions and the incorporation of the compounds into protein crystals are
      discussed. As an example of incorporation via cocrystallization, the
      incorporation of B3C into bovine trypsin, resulting in a single site with high
      occupancy, is described.

PMID- 19851025
TI  - Cloning and functional analysis of an allene oxide synthase in Physcomitrella
      patens.
AB  - Jasmonic acid (JA) is a plant hormone that plays important roles in a large
      number of processes in stress adaptation and development in flowering plants. A
      search of genome database indicated the existence of allene oxide synthase (AOS),
      an enzyme of JA biosynthesis, in Physcomitrella patens, a model plant among
      mosses. In this study, the presence of JA was detected in P. patens. The
      recombinant AOS of P. patens, which was overexpressed in Escherichia coli, showed
      AOS activity. These data suggest that the octadecanoid pathway also exists in P.
      patens.

PMID- 19851026
TI  - Dynamic motion affects metallic stent fractures.

PMID- 19851027
TI  - Transradial coronary intervention as the primary approach for acute myocardial
      infarction.

PMID- 19851028
TI  - Statin treatment in patients with metabolic syndrome and coronary artery disease.

PMID- 19851029
TI  - Cosmic effect of rosuvastatin in COSMOS.

PMID- 19851030
TI  - Mitochondrial protection and the reversal of left ventricular remodeling.

PMID- 19851031
TI  - Heart failure and sleep apnea.

PMID- 19851032
TI  - Possible contribution of 2-aminoethoxydiphenyl-borate-sensitive Ca2+ mobilization
      to adrenocorticotropin-induced glucocorticoid synthesis in rat adrenocortical
      cells.
AB  - Cytoplasmic calcium ([Ca(2+)](i)) provided through voltage-dependent Ca(2+)
      channels (VDCC) plays an important role in adrenocorticotropin (ACTH)-induced
      steroidogenesis in adrenocortical cells. To identify alternative mechanisms for
      [Ca(2+)](i) supply, we investigated the 2-aminoethoxydiphenyl borate (2APB)
      sensitive pathway as one of the possible signaling pathways involved in
      [Ca(2+)](i) supply for ACTH-induced steroidogenesis. In monolayers of cultured
      rat adrenal fasciculate and reticularis cells, ACTH at 10(-11) M stimulated
      corticosterone synthesis without increasing intracellular cAMP, and
      corticosterone synthesis was decreased by 10 microM 2APB by 51.8% (6.71 +/- 0.97
      vs. 3.23 +/- 0.05 ng/mL/4 hours; p<0.05). Furthermore, 2APB significantly
      decreased the 10(-11) M ACTH-stimulated [Ca(2+)](i). ACTH increased the
      intracellular inositol-1,4,5-trisphosphate (IP3) content with a peak at 10(-13) M
      ACTH, which illustrates the possibility that ACTH activates IP3/diacylglycerol-
      dependent protein kinase C signal transduction. However, the difference in ACTH
      concentrations between that responsible for the IP3 increase and steroidogenesis
      without elevated cAMP, suggest a hypothesis that IP3 is not required for
      steroidogenesis, but does involve an unknown messenger, which stimulates the
      release of Ca(2+) from the ER or the subsequent store-operated Ca(2+) entry
      (SOCE). The pregnenolone concentration in the culture medium was increased by
      ACTH, which was significantly suppressed by 2APB, showing that the 2APB-sensitive
      Ca(2+) supply affects cholesterol transport into the mitochondrial membrane via
      steroidogenic acute regulatory protein. Therefore, the SOCE may contribute to
      ACTH-induced steroidogenesis in the mitochondrial region. In conclusion, the
      [Ca(2+)](i) used for steroidogenesis may be derived from a 2APB-sensitive pathway
      and via VDCCs, particularly at physiological concentrations of ACTH. We suggest
      that ACTH receptors activate steroidogenesis via inositol triphosphate, or an
      unknown downstream messenger, which could be inhibited by 2APB.

PMID- 19851033
TI  - Effects of estrogen on PMCA 2 and 4 in human fibroblast-like synovial cells and
      mouse macrophage-like cells.
AB  - We investigated the possible roles of estrogen on plasma membrane Ca(2+)-ATPase
      (PMCA) in human fibroblast-like synovial cells (HFLS) and mouse macrophage-like
      cells (RAW 264.7). Western blots revealed the expression of PMCA 2 and 4 in both
      cells. In vitro treatments with 17beta-estradiol for 24 hours resulted in a
      concentration dependent decrease in PMCA expression. Moreover, Ca(2+)-ATPase
      specific activity was similarly decreased with estrogen treatments. However,
      treatments for 1 hour in the presence or absence of cycloheximide demonstrated
      non-significant effects. These results suggest that estrogen has a modulatory
      role on Ca(2+) homeostasis through decreasing PMCA expression and abating their
      activity.

PMID- 19851034
TI  - miRNA expression in a human papillary thyroid carcinoma cell line varies with
      invasiveness.
AB  - The purpose of these studies was to explore the expression pattern of miRNAs
      associated with invasion and metastasis of human papillary thyroid carcinoma
      (PTC). A transwell invasion chamber was used to select progressively more
      invasive cancer cell populations from a clonal cell line of human PTC with
      cervical lymph node metastasis, IHH-4. Three sublines with progressive
      invasiveness, designated IHH-4M-1, IHH-4M-2 and IHH-4M-3, were obtained through
      this in vitro selection process. The sublines manifested an increase in colony
      forming ability on soft agar and metastatic potency in nude mice. Then metastasis
      related miRNAs differentially expressed between them were analyzed utilizing the
      miRNA microarray technique. We found that 11 metastasis-related miRNAs were
      differentially expressed between the invasive subpopulations and their control
      subpopulations; these miRNAs may account for their significant difference in the
      invasion capabilities and favor lymphatic metastasis of PTC.

PMID- 19851035
TI  - Role of central leptin signaling in renal macrophage infiltration.
AB  - Monocytes/macrophages are key mediators of wound repair, tissue remodeling, and
      inflammation. However, the molecular mechanisms underlying macrophage recruitment
      to the site of inflammation is not fully understood. Leptin acts directly on the
      hypothalamus, thereby regulating food intake and energy expenditure. The leptin
      receptor, a single transmembrane protein that belongs to the gp130 family of
      cytokine receptor superfamily, is expressed not only in the hypothalamus but in a
      variety of peripheral tissues, suggesting the role of leptin as a pro
      inflammatory adipocytokine in peripheral tissues. Here, we show that deficiency
      of leptin signaling reduces renal macrophage infiltration after unilateral
      ureteral obstruction (UUO). Bone marrow transplantation studies using leptin
      signaling-deficient db/db mice revealed that leptin signaling in bone marrow
      cells may not play a major role in the UUO-induced renal macrophage infiltration.
      Interestingly, central leptin administration reverses the otherwise reduced UUO
      induced renal macrophage infiltration in leptin-deficient ob/ob mice. This is
      effectively abolished by central co-administration of SHU9119, a melanocortin-3
      receptor/melanocortin-4 receptor antagonist. This study demonstrates that central
      leptin administration in ob/ ob mice accelerates renal macrophage infiltration
      through the melanocortin system, thereby suggesting that the central nervous
      system, which is inherent to integrate information from throughout the organism,
      is able to control peripheral inflammation.

PMID- 19851036
TI  - A long-term follow-up of serum myeloperoxidase antineutrophil cytoplasmic
      antibodies (MPO-ANCA) in patients with Graves disease treated with
      propylthiouracil.
AB  - Propylthiouracil (PTU) is known to induce myeloperoxidase antineutrophil
      cytoplasmic antibodies (MPO-ANCA) in patients with Graves disease (GD).
      Previously, we showed that serum MPO-ANCA were frequently seen in patients with
      GD treated with PTU. In this study, we analyzed 13 patients with positive MPO
      ANCA examining a long-term clinical consequence of these patients as well as
      antibody titers during 5.6 +/- 3.0 years. PTU therapy was continued in 8 patients
      and discontinued in 5 patients. Antibody titers decreased in 7 of 8 patients who
      discontinued PTU therapy but remained positive in 5 patients 5 years after PTU
      withdrawal. The initial MPO-ANCA levels were significantly higher in those
      antibody titers remained positive for longer than 5 years (n=5) than in those
      titers turned to be negative within 5 years after PTU withdrawal (n=3) (203 +/-
      256 EU and 22 +/- 2 EU, respectively, P=0.04), but there were no significant
      differences in age, gender, duration of PTU therapy or dosage of PTU. Among 5
      patients who continued PTU therapy, 2 patients with initially low MPO-ANCA titers
      turned to having negative antibody. No patients had new symptoms or signs of
      vasculitis throughout the follow-up periods. The long-term follow-up study
      suggests that higher MPO-ANCA levels remain positive for years after PTU
      withdrawal but are rarely associated with vasculitis.

PMID- 19851037
TI  - Comparison between essential hypertension and pregnancy-induced hypertension: a
      genetic perspective.
AB  - Essential hypertension (EH) accounts for 80-90% of hypertension, and pregnancy
      induced hypertension (PIH) is responsible for hypertension during pregnancy. Both
      considered multifactorial disorders. While both have many features in common,
      conditions and causes of these diseases have yet to be clarified. Since both
      diseases are associated with hypertension, the genetic backgrounds may contain
      common features. The present study reviewed similarities and differences between
      women with EH and PIH, with a particular focus on their genetic backgrounds.

PMID- 19851038
TI  - Serum lipids and bone metabolism in Spanish men: the Camargo cohort study.
AB  - There is growing evidence of a link between lipid and bone metabolism, although
      data on this association in European men are scarce. This cross-sectional study
      from a community-based prospective cohort aims to explore the association of
      serum lipids with different aspects of bone metabolism in Spanish men.
      Demographic and anthropometric measurements, biochemical parameters including
      serum lipids, bone remodelling markers and calciotropic hormones, bone mineral
      density (BMD) assessed by dual X-ray absorptiometry and heel quantitative
      ultrasound, and prevalent vertebral and non-vertebral fractures, were evaluated
      in 289 men. Calciotropic hormones or bone markers were not associated with serum
      lipids. Serum total (TC) and LDL cholesterol, as well as LDL/HDL ratio were
      positively correlated to BMD at lumbar spine and hip. No significant correlation
      was noted for triglycerides or HDL. We observed a positive association between
      triglycerides, LDL/HDL ratio and BUA, and between TC/HDL ratio and both, QUI and
      BUA. BMD at the femoral neck and total hip was significantly higher in men with
      hypercholesterolemia after controlling for all the covariates (p=0.007). We did
      not observe any association between serum lipids and prevalent vertebral
      fractures. However, we found that TC (p=0.03) and LDL (p=0.04) were lower in
      subjects with non-vertebral fractures. In conclusion, we have found that a more
      unfavorable lipid profile (mainly higher LDL-C levels) is associated with higher
      BMD at lumbar spine and hip in Spanish men. Moreover, we did not observe any
      association between hypercholesterolemia and prevalent vertebral fractures, but
      we found lower serum TC and LDL-C levels in men with prevalent non-vertebral
      fractures.

PMID- 19851039
TI  - Chronic exposures to cholinesterase-inhibiting pesticides adversely affect
      respiratory health of agricultural workers in India.
AB  - OBJECTIVE: The impact of long term exposure to cholinesterase (ChE)-inhibiting
      organophosphate (OP) and carbamate (C) pesticides on the respiratory health of
      agricultural workers in India was investigated. METHODS: Three hundred and
      seventy-six nonsmoking agricultural workers (median age 41 yr) from eastern India
      who sprayed OP and C pesticides in the field and 348 age- and sex-matched control
      subjects with non-agricultural occupations from the same locality were enrolled.
      Prevalence of respiratory symptoms was obtained by questionnaire survey, and
      pulmonary function tests were carried out by spirometry. Chronic obstructive
      pulmonary disease (COPD) was diagnosed by the Global Obstructive Lung Disease
      (GOLD) criteria, and erythrocyte acetylcholinesterase (AChE) was measured by the
      Ellman method. RESULTS: Agricultural workers had greater prevalences of upper and
      lower respiratory symptoms, and appreciable reduction in spirometric
      measurements. Overall, lung function reduction was noted in 48.9% of agricultural
      workers compared with 22.7% of control, and a restrictive type of deficit was
      predominant. COPD was diagnosed in 10.9% of agricultural workers compared with
      3.4% of controls (p<0.05 in chi(2) test), and the severity of the disease was
      greater in agricultural workers. Red blood cell (RBC) AChE was lowered by 34.2%
      in agricultural workers, and the fall in AChE level was positively associated
      with respiratory symptoms, lung function decrement and COPD after controlling for
      education and income as potential confounders. CONCLUSIONS: Long-term exposure to
      cholinesterase-inhibiting agricultural pesticides currently in use in India is
      associated with a reduction in lung function, COPD and a rise in respiratory
      symptoms.

PMID- 19851040
TI  - Genotoxicity studies of heavy metals: lead, bismuth, indium, silver and antimony.
AB  - OBJECTIVES: Many kinds of heavy metals are used in industry; thus, it is
      important for us to clarify their toxicity. For example, lead, which is a
      component of solder, is notorious for its neurotoxicity, and substitute materials
      have been sought for many years. Therefore, we examined the genotoxicity of lead
      and also those of metallic bismuth, indium, silver and antimony which are
      possible substitutes for lead in solder. METHODS: Bacterial reverse mutation
      tests and chromosomal aberration tests in cultured mammalian cells were performed
      according to standard procedures. RESULTS: Antimony showed genotoxicity in both
      tests, and bismuth also showed positive results in the chromosomal aberration
      test. In contrast, lead, indium, and silver were considered to be inactive by the
      criteria of the present study. CONCLUSIONS: Although further studies are needed
      because of the difficulty of genotoxicity evaluation using an in vitro system,
      sufficient precautions should be made when antimony and bismuth are used.

PMID- 19851041
TI  - Alteration of radioprotective effects of heat-killed Lactobacillus casei in X
      irradiated C3H/He mouse related to blood level of proinflammatory cytokines by
      corticoids.
AB  - It is well known that a pre-administration of proinflammatory cytokines alters
      hematopoietic progenitor cells to promote an increase resistance against
      radiation and increases the survival rate in mice irradiated with lethal doses of
      radiation. Inflammation stimulators, such as some bacterial constituents, are
      also reported to have similar radioprotective action. We found that pre
      administration of heat-killed Lactobacillus casei (HLC) to mice increases the
      level of interleukin (IL)-1 beta in circulation as well as the survival rate
      following lethal dose of radiation. Since HLC stimulates early immune responses,
      effects by drugs to modify inflammation were studied. The increase of both blood
      IL-1 beta levels and survival rates by HLC were simultaneously accelerated by
      coadministration of mineralocorticoid and inhibited by glucocorticoids or
      corticotropin. Neither parameter was modified by non-steroidal anti-inflammatory
      or anti-rheumatoid drugs. This suggests that both expected radioprotective action
      and unexpected systemic action, realized as an increase in plasma cytokines, by
      inflammation-related radioprotectors can be controlled by the coadministration of
      drugs at least in C3H/He mice, based on consideration of their pharmacological
      properties.

PMID- 19851042
TI  - Transplantation of mesenchymal stem cells to prevent radiation-induced intestinal
      injury in mice.
AB  - The effective treatments of radiation-induced intestinal injury are currently
      unavailable. Developing new treatments for radiation-induced intestinal injury is
      thus important. The present study investigated whether transplantation of
      mesenchymal stem cells (MSCs) is able to prevent radiation-induced intestinal
      injury. Intestines of female nude mice (ICR nu/nu) were irradiated at a single
      dose of 30 Gy. Transplantation of male MSCs (C57BL/6) was then immediately
      performed into the walls of irradiated intestine by direct injection for the
      irradiation + MSCs group. Mice were weighed daily and survival was recorded for
      13 days after irradiation. From 13 to 27 days after irradiation, intestines of
      mice were obtained in order to assay histological changes by staining with
      hematoxylin-eosin and Masson trichrome. Mean body weight of the irradiation + MSC
      group was significantly higher than that of the irradiation-only group from 8
      days after irradiation. In addition, survival rates were significantly higher in
      the irradiation + MSC group than for the irradiation-only group from 5 days after
      irradiation. Histological observation revealed that intestines of irradiation +
      MSC-transplanted mice were thick in the submucosal and muscle layers, and had
      almost fully recovered from radiation-induced intestinal injury at day 27.
      Specifically, ulcerated areas in the intestines of the irradiation + MSC
      transplanted mice were smaller by 13 days after irradiation and were fewer in
      numbers at 27 days when compared with the irradiation-only group. Our results
      suggest that transplanted MSCs may play an important role in preventing radiation
      induced injury and may offer a novel method to treat radiation-induced intestinal
      injury.

PMID- 19851043
TI  - Imaging of peripheral-type benzodiazepine receptor in tumor: carbon ion
      irradiation reduced the uptake of a positron emission tomography ligand [11C]DAC
      in tumor.
AB  - We aimed to determine the effect of carbon ion irradiation on the uptake of N
      benzyl-N-11C-methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9
      yl)acetamide ([(11)C]DAC), a positron emission tomography (PET) ligand for the
      peripheral-type benzodiazepine receptor (PBR), in tumor cells and tumor-bearing
      mice. Spontaneous murine fibrosarcoma (NFSa) cells were implanted into the right
      hind legs of syngeneic C3H male mice. Conditioning irradiation with 290 MeV/u
      carbon ions was delivered to the 7- to 8-mm tumors In vitro uptake of [(11)C]DAC
      was measured in single NFSa cells isolated from NFSa-bearing mice after
      irradiation. In vivo biodistribution of [(11)C]DAC in NFSa-bearing mice was
      determined by small animal PET scanning and dissection. In vitro autoradiography
      was performed using tumor sections prepared from mice after PET scanning. In
      vitro and in vivo uptake of [(11)C]DAC in single NFSa cells and NFSa-bearing mice
      was significantly reduced by carbon ion irradiation. The decrease in [(11)C]DAC
      uptake in the tumor sections was mainly due to the change in PBR expression. In
      conclusion, [(11)C]DAC PET responded to the change in PBR expression in tumors
      caused by carbon ion irradiation in this study. Thus, [(11)C]DAC is a promising
      predictor for evaluating the effect of carbon ion radiotherapy.

PMID- 19851044
TI  - Post-dauer life span of Caenorhabditis elegans dauer larvae can be modified by X
      irradiation.
AB  - The time spent as a dauer larva does not affect adult life span in Caenorhabditis
      elegans, as if aging is suspended in this quiescent developmental stage. We now
      report that modest doses X-irradiation of dauer larvae increased their post-dauer
      longevity. Post-irradiation incubation of young dauer larvae did not modify this
      beneficial effect of radiation. Conversely, holding dauer larvae prior to
      irradiation rendered them refractory to this X-radiation-induced response. We
      present a model to explain these results. These experiments demonstrate that
      dauer larvae provide an excellent opportunity to study mechanisms by which X
      irradiation can extend life span.

PMID- 19851046
TI  - Cardiac autonomic imbalance in children with allergic rhinitis.
AB  - The involvement of autonomic imbalance has been reported in the pathogenesis of
      hypersensitivity reactions. Allergic diseases are more frequent in children and
      some of predisposing factors may be changed according to the increasing age, but
      the involvement of autonomic imbalance has not been investigated in pediatric
      population. In this cross-sectional, case-control study, we evaluated the
      autonomic system by measuring heart rate variability (HRV) in pediatric patients
      with allergic rhinitis. Thirty-five pediatric patients with allergic rhinitis and
      36 healthy children (mean age 11 +/- 2.7, and 12 +/- 3 years, respectively) were
      enrolled in the study. Age and gender were not different between the groups. The
      diagnosis of allergic rhinitis was based on the history, symptoms, and skin prick
      tests. Participants with acute infection, nasal polyposis, bronchial asthma, and
      any other medical problems, assessed by history, physical examination and routine
      laboratory tests, were excluded. Twenty-four hour ambulatory electrocardiographic
      recordings were obtained, and the time domain and frequency domain indices of HRV
      were analyzed. We found significant increase in calculated HRV variables in
      children with allergic rhinitis compared to controls, which reflect
      parasympathetic tones, such as number of R-R intervals exceeding 50 ms, root mean
      square of successive differences between normal sinus R-R intervals, the
      percentage of difference between adjacent normal R-R intervals, and high
      frequency. These results indicate that HRV is increased, which implies
      sympathetic withdrawal and parasympathetic predominance. We propose that
      autonomic imbalance may be involved in the pathophysiology of allergic rhinitis
      in pediatric patients.

PMID- 19851045
TI  - Cisplatin ototoxicity and protection: clinical and experimental studies.
AB  - Cisplatin is a chemotherapeutic agent that is widely used to treat a variety of
      malignant tumors. Serious dose-limiting side effects like ototoxicity,
      nephrotoxicity and neurotoxicity occur with the use of this agent. This review
      summarizes recent important clinical and experimental investigations of cisplatin
      ototoxicity. It also discusses the utility of protective agents employed in
      patients and in experimental animals. The future strategies for limiting
      cisplatin ototoxicity will need to avoid interference with the therapeutic effect
      of cisplatin in order to enhance the quality of life of patients receiving this
      important anti-tumor agent.

PMID- 19851047
TI  - High concentrations of reactive oxygen species in the BAL fluid are correlated
      with lung injury in rabbits after hemorrhagic shock and resuscitation.
AB  - Increased levels of cytokines or reactive oxygen species (ROS) in the
      bronchoalveolar lavage (BAL) fluid are associated with acute lung injury after
      ischemia/reperfusion. We investigated the correlation of these markers with the
      degree of lung injury in a rabbit model of hemorrhagic shock. Rabbits, maintained
      by mechanical ventilation, were left untreated (control) or subjected to
      hemorrhagic shock by withdrawing blood (n = 12 for each group). Shock animals
      were re-infused their shed blood for resuscitation. At the end of the experiment,
      BAL fluid was recovered, in which parameters of oxidative stress and cytokines
      were measured. Macrophages and malondialdehyde levels were increased (p = 0.043
      and p = 0.003, respectively), and total antioxidant capacity (TAC) was decreased
      in the shock animals compared with control (p = 0.009). Production of ROS was
      significantly enhanced in shock animals compared with controls (p < 0.001). BAL
      fluid levels of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were
      higher in shock rabbits by more than twofold (p < 0.001 for each). Shock animals
      also showed higher histopathological scores that represent severe tissue damage
      than controls (p = 0.022). Numbers of macrophages and levels of ROS and TAC were
      correlated with the degree of lung injury (p = 0.006, p = 0.02, and p = 0.04,
      respectively), but not cytokines. Therefore, resuscitation from hemorrhagic shock
      results in acute lung injury, with enhanced pulmonary oxidative and inflammatory
      responses. In conclusion, ROS in the BAL fluid are good markers that predict lung
      injury following hemorrhagic shock and resuscitation.

PMID- 19851048
TI  - Chronic carbon monoxide exposure is associated with the increases in carotid
      intima-media thickness and C-reactive protein level.
AB  - Being the most common cause of death from poisoning worldwide, cardiovascular
      manifestations of acute carbon monoxide (CO) poisoning have been subject of
      various studies but current evidence about effects of chronic CO exposure on
      atherosclerosis is limited which is very common. We aimed to investigate
      association of chronic CO exposure with atherosclerosis by measuring carotid
      intima-media thickness (CIMT) and high-sensitivity C-reactive protein (hs-CRP).
      Forty healthy male non-smoker indoor barbecue workers (mean age; 33.0 +/- 9.0
      years) working in different restaurants for at least three years and 48 age
      matched healthy men (mean age; 34.3 +/- 6.6 years) enrolled in the study.
      Clinical characteristics of indoor barbecue workers and control group were
      comparable in terms of body mass index, blood pressure, and lipid profile.
      However, carboxyhemoglobin (COHb) (6.4 +/- 1.5% vs. 2.0 +/- 1.1%), hs-CRP (2.7 +/
      2.0 mg/L vs. 1.1 +/- 0.8 mg/L) and CIMT (1.1 +/- 0.3 mm vs. 0.9 +/- 0.1 mm) were
      higher in indoor barbecue workers (p < 0.001 for each). In Pearson correlation
      analysis, CIMT was correlated with COHb concentration (r = 0.635, p < 0.001) and
      hs-CRP level (r = 0.466, p < 0.001). Among indoor barbecue workers, the years
      worked (years exposed to CO) are correlated with COHb, hs-CRP and CIMT. In
      multivariate analysis, COHb concentration is the only independent predictor of
      CIMT (beta = 0.571, p < 0.001). The increased CIMT and hs-CRP in indoor barbecue
      workers suggest that chronic CO exposure may increase the risk of atherosclerotic
      cardiovascular events.

PMID- 19851049
TI  - Lower morbidity and disease risk among the Chinese medicine physicians in Taiwan.
AB  - Healthy physicians are critical to the quality of care for patients. There is a
      common trend in Chinese societies seeking for medical treatments from Chinese
      medicine physicians. However, there are limited studies that investigated the
      health status for the Chinese medicine physicians. In this report, we used
      National Health Insurance Research database of Taiwan between 1998 and 2002 to
      compare the morbidities between Chinese medicine physicians and general
      population. The number of Chinese medicine physicians in this study is 6,143
      (5,036 males with the mean age of 40.47 years and 1,107 females with the mean age
      of 36.24 years), and the number of the referent subjects is 24,576, randomly
      selected from the database matching by sex and age. We found that the Chinese
      medicine physicians have lower all-causes morbidity (86% vs. 95%, p < 0.001),
      except that female Chinese medicine physicians had significantly higher rates of
      complications of pregnancy, childbirth, and puerperium than female population.
      Such an exception might reflect a consequence of maternal age effect. The odds
      ratio between all causes and two comparison groups was 0.36 (95% CI: 0.33, 0.40),
      indicating that the Chinese medicine physicians have much lower disease risk.
      Higher education, better socioeconomic status, and good knowledge in medicine
      (possible self-treatment) may explain the observed differences. Among the Chinese
      medicine physicians, the morbidity rate of male subjects is lower than the female
      subjects (85.9% vs. 91.4%, p < 0.001). This study will provide the helpful
      information in guiding future investigations about health hazards to the practice
      of Chinese medicine.

PMID- 19851050
TI  - Protective action of D-ribose against renal injury caused by ischemia and
      reperfusion in rats with transient hyperglycemia.
AB  - Hyperglycemia amplifies the inflammatory state after ischemia/reperfusion (I/R),
      and activated neutrophils have been implicated in the development of I/R-induced
      renal injuries. D-ribose is a naturally occurring monosaccharide found in all
      living cells. In this study, we examined whether D-ribose attenuates I/R-induced
      renal injury by reducing neutrophil activation in rats with transient
      hyperglycemia. Male Wistar rats were divided into sham (n = 24), control (n =
      64), and D-ribose (n = 32) groups. Rats received intraperitoneal injection of
      glucose (3 g/kg) 30 min before induction of ischemia to induce transient
      hyperglycemia. Anesthetized rats underwent right nephrectomy and subsequent
      occlusion of the left renal artery and vein for 45 min. D-ribose (400 mg/kg) was
      intravenously administered 30 min before induction of ischemia. D-ribose
      significantly reduced the degree of the I/R-induced increases in renal
      concentrations of cytokine-induced neutrophil chemoattractant-1 (a chemotactic
      factor for the activation of neutrophils and chemotaxis to the site of injury)
      and myeloperoxidase (an indicator of neutrophils infiltration). D-ribose also
      reduced the I/R-induced increases in serum levels of blood urea nitrogen and
      creatinine, and improved histological changes, including acute tubular necrosis
      in the corticomedullary junction fields. These results indicate that D-ribose
      reduces the I/R-induced acute renal injury in rats with transient hyperglycemia,
      probably by reducing neutrophil activation. D-ribose might thus be useful for
      surgical procedures, such as renal transplant surgery, under hyperglycemia.

PMID- 19851051
TI  - Demographic and socioeconomic determinants of the use of periodic health
      examinations: public vs. private sector.
AB  - Periodic health examinations (PHEs) are prevalent in Korea. While some people
      frequently use public PHEs, others use private PHEs with high fees. This study
      examined the determinants of the use of public and private PHEs using a
      multinomial logit model. We used the data from the Korean Longitudinal Study of
      Aging (KLoSA) Wave I conducted in 2006. The KLoSA was a national longitudinal
      study of a representative sample of individuals (n = 10,253) aged 45 years or
      older. The mean age of the sample was 61.6 years; 77.8% of subjects were married
      and 37.5% had at least a high school education. The most frequent type of PHE
      usage was public PHEs only (38.9%), followed by private PHEs only (7.3%) and both
      public and private PHEs (6.5%). This study found that subjects who lived in rural
      areas or who were employed were significantly more likely to use public PHEs
      because of many public health facilities in rural area and mandatory public PHEs
      for employees. Those who used private PHEs only were educated, wealthy, or
      unhealthy, because private PHEs required out-of-pocket payments and provided
      higher quality services. Those who used both types of PHE had a high socio
      economic status or a bad health status. The authors suggest that policy makers
      pay attention to the use of public PHEs among populations with lower socio
      economic status. As for the group of subjects who use both types of PHE, their
      overutilization of PHEs must be reduced through cooperation between the public
      and private PHEs.

PMID- 19851052
TI  - Predictors of Japanese workers' motivation to use the results of worksite health
      checkups in their daily health management.
AB  - Japanese law stipulates that workers undergo worksite health checkups. If workers
      do not use their results of those checkups in their daily health management, the
      merit of this law will not be realized. Therefore, it is important to identify
      the predictors to improve their motivation to use the results of health checkups.
      We investigated those predictors by using a questionnaire survey. Multiple linear
      regression analysis was conducted for 1,791 subjects (1,530 males and 261
      females) at a Japanese manufacturing plant. The average age of enrolled subjects
      was 42.0 years (standard deviation [S.D.], 13.4 years). The average age of male
      subjects was 42.3 (S.D., 13.8) years and that of the female subjects was 39.9
      (S.D., 10.4) years. The results revealed that as workers advanced in age, they
      maintained their motivation more to use those results. Women maintained their
      motivation more than men. Workers who believe that their health depends on the
      influence from physicians and healthcare providers in hospitals felt motivated.
      Workers who realized the effectiveness of those checkups to maintain good health,
      who knew how to adopt an appropriate lifestyle, and who were given consultations
      with physicians when they received their health checkups, felt motivated.
      Regarding the healthcare organizations' and occupational health staffs'
      responsibilities, only detecting illness early is not sufficient. Those
      healthcare providers must value more primary prevention. Our findings can be
      applied to various occupational health activities, including health
      consultations, health education seminars, and providing appropriate instruction
      on how to interpret the results of the worksite health checkups.

PMID- 19851053
TI  - Treatment strategy for combined carotid artery stenosis and coronary artery
      disease: staged or simultaneous surgical procedure?
AB  - Patients with combined carotid and coronary arterial diseases pose a high risk of
      cerebrovascular events, and the treatment of choice with either a simultaneous or
      a staged surgical procedure remains controversial. The literature of combined
      carotid and coronary arterial diseases of a recent decade in English was
      retrieved. Totally 41,901 patients undergoing simultaneous or staged carotid and
      coronary procedures from 53 reports were included. As a result, carotid
      endarterectomy plus coronary artery bypass remained the most commonly used
      procedure for the intervention of combined carotid artery stenosis and coronary
      artery disease, and was associated with higher incidences of perioperative
      transient ischemic attack, stroke and hospital mortality, but with less
      perioperative myocardial infarction comparing with the staged procedures.
      Patients with a simultaneous carotid endarterectomy and coronary artery bypass
      were generally related more to an advanced atherosclerotic coronary artery
      disease, so that a pure comparison between the two strategies was not always
      possible. To compare the efficacy of different surgical methods for combined
      carotid and coronary arterial diseases is of pronounced importance. The new
      hybrid approach consisting of the simultaneous carotid artery stenting and
      subsequent on-pump coronary artery bypass can be a safe approach, with the aim to
      reduce the surgical trauma as compared to surgical procedures, and to reduce the
      risk of myocardial infarction in the interval period required for the staged
      operations. Thus, for patients with combined carotid artery stenosis and coronary
      artery disease, the simultaneous surgical procedure, rather than the staged
      procedure, is recommended.

PMID- 19851054
TI  - Emergency cesarean section as a result of acute eosinophilic pneumonia during
      pregnancy.
AB  - Acute eosinophilic pneumonia is a disease of unknown etiology characterized by
      peripheral blood eosinophilia and pulmonary infiltrative shadows on radiography.
      Acute eosinophilic pneumonia follows an acute course within 1 week and the
      symptoms include fever, dyspnea, and cough. Acute eosinophilic pneumonia has a
      good prognosis and responds promptly to steroid treatments. Here we present a
      critical case of acute eosinophilic pneumonia during pregnancy, which led to
      emergency cesarean section because of fetal distress. The patient was a 24-year
      old gravida at 34 + 6 weeks gestation, with fever, and an elevated CRP; thus
      antibiotics were started. At 35 + 1 weeks gestation, cardiotocography (CTG)
      revealed late decelerations, fetal distress was diagnosed, and an emergency
      cesarean section was performed. The pre-operative maternal blood gas analysis
      showed a low PaO(2) of 55.7 mmHg and a chest X-ray revealed ground-glass
      opacities and pleural effusions in the middle lower lung fields bilaterally. A
      male of 2,336 g in weight was delivered with Apgar scores of 8 and 8 at 1 and 5
      min, respectively. Due to the clinical progress and the elevated eosinophil count
      (532/microl) in the peripheral blood differential leukocyte count, the diagnosis
      of acute eosinophilic pneumonia was made. With the administration of oxygen and
      steroid treatment, the patient's general condition recovered. Both the mother and
      the baby were discharged on the 10(th) post-operative day and the patient has
      been leading a normal life with no recurrence for > 3 years since delivery.

PMID- 19851055
TI  - Establishment of a guinea pig model of latent tuberculosis with GFP-introduced
      Mycobacterium tuberculosis.
AB  - There exists latent tuberculosis, in which small numbers of tubercle bacilli
      remain viable in the host without visible granulomatous lesions. As few data
      exist on the mechanisms of latent tuberculosis, it is important to examine latent
      tuberculosis in terms of pathogenesis and efficacy of chemotherapy. As a first
      step, we used green fluorescent protein (GFP)-introduced H37Rv Mycobacterium
      tuberculosis to establish latent tuberculosis in the guinea pig that provides one
      of the best animal models of tuberculosis. We inoculated the guinea pigs
      subcutaneously with 100 or 1,000 colony-forming unit (CFU) of tubercle bacilli.
      During the 300-day follow-up period after infection, there were no clinical signs
      of disease, suggesting a lack of visible granulomatous lesions. In fact, upon
      necropsy, no macroscopic tuberculous lesions were recognized, but
      histopathological examination of the lung, spleen and liver revealed
      microgranulomas consisting of epithelioid macrophages and lymphocytes without
      central necrosis. Importantly, photon imaging visualized granulomatous lesions
      corresponding to these histologically apparent microgranulomas. Tuberculin skin
      testing of infected guinea pigs showed strong positivity (> or = 10 mm
      induration) until the end of the experiments. Real-time PCR analysis showed a
      significant increase in the expression levels of interferon-gamma, tumor necrosis
      factor-alpha, interleukin-12, and inducible nitric oxide synthase mRNAs in
      infected lung tissues after 300 days (P < 0.01). As human samples are hardly
      available to study latent tuberculosis, our guinea pig model would be useful for
      examining the pathogenesis and molecular mechanisms of latent tuberculosis as
      well as for monitoring the results of chemotherapy with green fluorescence
      emission of tubercle bacilli.

PMID- 19851056
TI  - Insulin receptor and IGF1R are not required for oocyte growth, differentiation,
      and maturation in mice.
AB  - In mammals, insulin and insulin-like growth factors (IGFs: IGF1 and IGF2) act
      through 2 structurally related receptors, the insulin receptor (INSR) and the
      type 1 IGF receptor (IGF1R), both of which are expressed in developing oocytes.
      IGF1 plays an important role in female reproduction, and female Igf1 knockout
      mice fail to ovulate and are infertile. On the other hand, little is known about
      the in vivo role of the insulin signaling pathway in oocytes during follicular
      development, although exposure to insulin or IGF1 in vitro improves oocyte
      maturation. To further address the significance of insulin/IGF signaling, we used
      conditional mutant mice and ablated the function of the genes encoding INSR,
      IGF1R, or both receptors specifically in developing mouse oocytes. Our genetic
      evidence showed unexpectedly that the female reproductive functions are not
      affected when Insr, Igf1r or both Insr;Igf1r are ablated in oocytes, as the
      female mice are fertile and exhibit normal estrous cyclicity, oocyte development
      and maturation, parturition frequency, and litter size. In view of these novel
      observations indicating that the insulin/IGF signaling is not essential in
      oocytes, the IGF1-dependent female fertility is re-evaluated and discussed.

PMID- 19851057
TI  - Functional analysis of novel androgen receptor mutations in a unique cohort of
      Indonesian patients with a disorder of sex development.
AB  - Mutations in the androgen receptor (AR) gene, rendering the AR protein partially
      or completely inactive, cause androgen insensitivity syndrome, which is a form of
      a 46,XY disorder of sex development (DSD). We present 3 novel AR variants found
      in a cohort of Indonesian DSD patients: p.I603N, p.P671S, and p.Q738R. The aim of
      this study was to determine the possible pathogenic nature of these newly found
      unclassified variants. To investigate the effect of these variants on AR
      function, we studied their impact on transcription activation, AR ligand-binding
      domain interaction with an FxxLF motif containing peptide, AR subcellular
      localization, and AR nuclear dynamics and DNA-binding. AR-I603N had completely
      lost its transcriptional activity due to disturbed DNA-binding capacity and did
      not show the 114-kDa hyperphosphorylated AR protein band normally detectable
      after hormone binding. The patient with AR-I603N displays a partial androgen
      insensitivity syndrome phenotype, which is explained by somatic mosaicism. A
      strongly reduced transcriptional activity was observed for AR-Q738R, together
      with diminished interaction with an FxxLF motif containing peptide. AR-P671S also
      showed reduced transactivation ability, but no change in DNA- or FxxLF-binding
      capacity and interferes with transcriptional activity for as yet unclear reasons.

PMID- 19851058
TI  - Space, gravity and the physiology of aging: parallel or convergent disciplines? A
      mini-review.
AB  - The abnormal physiology that manifests itself in healthy humans during their
      adaptation to the microgravity of space has all the features of accelerated
      aging. The mechano-skeletal and vestibulo-neuromuscular stimuli which are below
      threshold in space, result in an overall greater than 10-fold more rapid onset
      and time course of muscle and bone atrophy in space and the development of
      balance and coordination problems on return to Earth than occur with aging.
      Similarly, the loss of functional capacity of the cardiovascular system that
      results in space and continuous bed rest is over 10 times faster than in the
      course of aging. Deconditioning in space from gravity deprivation has brought
      attention to the medical hazards of deconditioning on Earth from gravity
      withdrawal as in sedentary aging. Though seemingly reversible after periods of 6
      months in space or its ground analog of bed rest, it remains to be seen whether
      that will be so after longer exposures. Both adaptation to space and aging do not
      merely parallel but converge as disorders of mechanotransduction. Like
      spaceflight, its analog bed rest telescopes the changes observed with aging and
      serves as a useful clinical model for the study of age-related deconditioning.
      The convergence of the disciplines of aging, along with gravitational and space
      physiology is advancing the understanding and prevention of modern lifestyle
      medical disorders.

PMID- 19851059
TI  - Marked improvement in nail psoriasis during treatment with adalimumab.
AB  - BACKGROUND: Nail involvement is known as a common finding in psoriatic patients
      and represents a significant impact on patients' quality of life. The treatment
      of nail psoriasis is often challenging, and there is a need for new therapeutic
      options. Biologicals effective in the treatment of moderate to severe chronic
      plaque psoriasis may represent a new therapeutic modality for this disease.
      Adalimumab is a fully human IgG1 monoclonal antibody that binds to tumor necrosis
      factor alpha with high affinity and specificity. OBSERVATIONS: We report two
      cases of rapid improvement in nail psoriasis under adalimumab monotherapy with
      maintained effectiveness despite intermittent treatment as well as long remission
      after therapy discontinuation. CONCLUSION: The marked improvement of our two
      cases indicates that adalimumab may also help ameliorate nail psoriasis and
      warrants further controlled studies to establish the effectiveness and
      therapeutic regimes.

PMID- 19851060
TI  - The effect of aminolevulinic acid photodynamic therapy on microcomedones and
      macrocomedones.
AB  - BACKGROUND: Photodynamic therapy (PDT) with aminolevulinic acid (ALA) has been
      shown to be an effective treatment for acne. However, the effect of ALA PDT on
      comedo formation has never been objectively evaluated. Cyanoacrylate follicular
      biopsy (CFB), a noninvasive procedure, has been proposed as the most reliable
      tool for studying follicular casts. OBJECTIVE: To determine the possible effect
      of ALA and red light (550-700 nm) on macro- and microcomedones in acne patients.
      PATIENTS AND METHODS: 10 patients with mild-to-moderate facial and/or chest/back
      acne resistant to conventional therapies received ALA PDT at 2-week intervals in
      3 sessions. The severity of acne had been estimated by a system of points, the
      Global Acne Grading System. The patients underwent PDT utilizing ALA 10% (face)
      or 15% (back/chest) and red light (15 J/cm(2) each session). CFBs were performed.
      RESULTS: Four weeks after their last PDT session, the patients showed an average
      global score reduction of 50%. CFBs demonstrated a reduction in the total area,
      the average area and the density of macrocomedones. CONCLUSION: The results
      obtained in this study using CFB evaluation demonstrate that ALA PDT exerts an
      action on the comedogenic phase as well.

PMID- 19851061
TI  - Renal protection by ischemic preconditioning is associated with p50/p50
      homodimers.
AB  - BACKGROUND: Although recent studies indicate that renal ischemia preconditioning
      (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise
      protection mechanism is still unknown. It has been widely recognized that the
      activity of nuclear factor-kappaB (NF-kappaB) is altered upon I/R injury.
      However, few studies have focused on the compositional change of NF-kappaB
      complexes. In the current study, we observed different NF-kappaB dimers in I/R
      and IPC, and postulated that p50 homodimers might represent the predominant NF
      kappaB activation in renal IPC. METHODS: 24 male SD rats were treated with a sham
      operation, I/R or IPC. While the right kidney was removed in all animals, I/R was
      induced by left renal artery clamping for 45 min, and IPC was induced by left
      renal artery clamping for 2 min, reperfused for 5 min, and repeated for 3 cycles
      before 45 min occlusion. After 24 h of reperfusion, we assessed NF-kappaB
      activities, composition of NF-kappaB, and expression of IL-18. RESULTS: Compared
      to the I/R group, NF-kappaB activity decreased significantly in the IPC group.
      Supershift assays were then performed to examine the NF-kappaB subunits in the
      binding complexes. In both the I/R and IPC groups, the composition of NF-kappaB
      contained p65 and p50. The densities of these two supershift bands were almost
      equivalent in the I/R group, suggesting the NF-kappaB composition was p50/p65
      dimers. However, the densities of p50 bands were more than twice that of p65 in
      the IPC group and the levels of Bcl-3 increased in parallel in these rats,
      suggesting that p50/p50 homodimers might dominate the NF-kappaB activities in
      renal IPC. Finally, the expression of IL-18, a marker of acute kidney injury, was
      significantly increased in the area of tubulointerstitium in the I/R group and
      attenuated in the IPC group. CONCLUSION: In conclusion, our investigation
      suggests that: (1) the general activity of NF-kappaB is attenuated in IPC
      kidneys, and (2) the remaining activation of NF-kappaB is dominated with p50/p50
      homodimer. Both of these effects might subsequently downregulate IL-18
      expression, as well as provide renal protective effects of IPC. Though we focused
      on the phenomenological observations in this study, the detailed mechanism is
      still to be determined.

PMID- 19851062
TI  - Dietary phytosterols and phytostanols alter the expression of sterol-regulatory
      genes in SHRSP and WKY inbred rats.
AB  - BACKGROUND/AIMS: We elucidated the molecular mechanism(s) underlying sterol
      trafficking by investigating alterations in gene expression in response to
      increased retention of dietary phytosterols and phytostanols in stroke-prone
      spontaneously hypertensive (SHRSP) and normotensive Wistar Kyoto (WKY) inbred
      rats. METHODS: SHRSP and WKY inbred rats were fed a control diet or a diet
      supplemented with phytosterols or phytostanols (2 g/kg diet). RESULTS: Intake of
      phytosterols and phytostanols increased their incorporation in plasma, red blood
      cells, liver, aorta and kidney, but decreased cholesterol levels in liver and
      aorta in both rat strains. Phytosterol intake up-regulated mRNA expression of
      intestinal Npc1l1 and Abcg8, and hepatic Abcg5, Abca1, Cyp27a1 and Hmgcr.
      Phytostanol intake up-regulated Npc1l1 and Srebp2, but down-regulated Abcg5 mRNA
      expression in small intestine. Phytostanols also up-regulated Abca1 expression in
      SHRSP rats, but down-regulated Abca1 expression in WKY inbred rats. Compared to
      phytosterols, dietary phytostanols reduced phytosterol levels in plasma, red
      blood cells, and kidney, as well as altered mRNA levels of hepatic Abca1,Cyp27a1,
      and Hmgcr and intestinal Abcg5/8, Hmgcr and Srebp2. CONCLUSIONS: Altered
      expression of multiple sterol-regulatory genes may contribute to the
      incorporation and cholesterol-lowering actions of phytosterols and phytostanols.
      Phytosterols and phytostanols may act through different mechanism(s) on
      cholesterol and phytosterol/phytostanol trafficking.

PMID- 19851063
TI  - Relation between body fat and liver fat accumulation and cytokine pattern in non
      alcoholic patients with chronic HCV infection.
AB  - BACKGROUND: Liver steatosis in chronic hepatitis C virus (HCV) infection is
      multifactorial. Therefore, there is not necessarily a relation between obesity
      and liver fat.On the other hand, body fat secretes cytokines, and cytokines and
      oxidative damage play important roles on progression of liver disease. METHODS:
      We analyzed the relationships between liver fat (assessed by histomorphometry)
      and trunk and subcutaneous fat (waist perimeter, triceps skinfold, BMI); the
      relationships between liver and body fat and cytokines (IL-6, TNF-alpha, IL-8,
      IFN-gamma, IL-4), adipokines (adiponectin and TIMP-1), and serum malondiladehyde
      and antioxidants (glutathione peroxidase and superoxide dismutase (SOD)
      activities); and the relationships of these data with histological changes in 40
      HCV-infected non-alcoholic patients. RESULTS: Significant correlations were found
      between liver fat and waist perimeter and BMI, and between serum TIMP-1 and liver
      fat. Serum TIMP-1 was significantly related to body fat stores; serum IL-6 and
      IFN-gamma were related to histological inflammation. Patients with waist
      perimeter >102 cm (men) or 88 cm (women) showed increased liver fat. In 38.8% of
      non-obese patients, liver fat accumulation was intense. CONCLUSIONS: There is a
      relationship between visceral fat, serum TIMP-1 and liver steatosis. However, at
      least in some patients, factors different from mere adiposity play a role in
      liver steatosis.

PMID- 19851064
TI  - Effects of neurotrophic factors on growth and glial cell alignment of cultured
      adult spiral ganglion cells.
AB  - Adult spiral ganglion cells were cultured in chorus to assess the influence of
      the neurotrophins brain-derived neurotrophic factor, neurotrophin 3 and glial
      cell line-derived neurotrophic factor (GDNF) on neurite growth and Schwann cell
      alignment. Over 1500 measurements were collected using each factor at 10 ng/ml
      and all three in combination. Evaluation was made with GDNF at concentrations of
      up to 100 ng/ml. Neurite dimensions were assessed at days 5, 7, 9 and 11 using a
      computer-based program (Axon Analyzer). GDNF had a strong effect on spiral
      ganglion cell growth almost attaining the level of all three factors in
      combination. GDNF increased glial cell alignment and nerve bundle formation.
      Results show the potential of GDNF to maintain and possibly restore auditory
      nerve integrity.

PMID- 19851065
TI  - Effects of selective serotonin reuptake inhibitor on treating tinnitus in
      patients stratified for presence of depression or anxiety.
AB  - We evaluated the effects of a selective serotonin reuptake inhibitor, paroxetine,
      on treating tinnitus.Tinnitus patients stratified for the presence of depression
      and anxiety were studied retrospectively. Fifty-six patients were observed for
      more than 6 months. They were initially treated with paroxetine only at a dose of
      10 mg/day for 2-4 weeks; thereafter, the dose was increased to 20 mg/day.
      Tinnitus distress was evaluated with the Tinnitus Handicap Inventory (THI) and
      with visual analog scales (VASs) for tinnitus loudness and annoyance. Depression
      and anxiety were measured with the Self-Rating Depression Scale (SDS) and the
      trait section of the State-Trait Anxiety Inventory (STAI). The patients were
      grouped according to their SDS and STAI scores, and each variable was compared at
      baseline and the 6-month follow-up. Changes among these variables were also
      examined to determine whether reduced tinnitus distress was related to the
      improvement of depression or anxiety. Patients with both depression and anxiety
      showed better results (decrease in THI, VASs, SDS and STAI scores) than patients
      with anxiety alone, or patients without depression and anxiety. In patients with
      depression and anxiety, changes in tinnitus variables and changes in depression
      and anxiety scores were strongly correlated. In other patients, however, changes
      in tinnitus variables and changes in depression and anxiety scores were not
      correlated. These results suggest that paroxetine is effective in treating
      distressed tinnitus patients with depression and anxiety by reducing their
      tinnitus severity as well as their depression and anxiety.

PMID- 19851066
TI  - Prognosis after cryptogenic cerebral ischemia in patients with coagulopathies.
AB  - BACKGROUND/AIM: Prognosis and optimal secondary prevention in ischemic stroke
      patients with coagulopathies remain unclear. The goal of this prospective
      observational multicenter study was to determine the risk of recurrence in
      cryptogenic stroke patients with either no or defined coagulopathies under
      various prevention regimens. METHODS: A total of 429 patients from 14 German
      stroke centers with an acute cryptogenic ischemic stroke or transient ischemic
      attack in whom specialized coagulation testing for inherited and acquired
      coagulopathies (factor V Leiden mutation/resistance to activated protein C,
      prothrombin mutation, deficiencies of protein C, protein S, antithrombin III,
      anticardiolipin IgG antibodies, lupus anticoagulant) had been performed were
      included. Biannual follow-up in 339 (79%) of these patients assessed recurrent
      cerebrovascular events and secondary prevention therapy during a mean period of
      2.5 years. RESULTS: A defined coagulopathy was detected in 89 patients with
      follow-up, whereas no coagulopathy could be found in 250 patients with follow-up
      (control group). The Kaplan-Meier estimate for recurrent ischemic stroke or
      transient ischemic attack after 3 years was 13.6% (95% CI: 5.9-21.2%) in patients
      with a coagulopathy compared to 9.3% (95% CI: 5.4-13.2%) in controls, which was
      not significant after adjustment for potential risk factors by Cox regression
      analysis. Only a previous cerebrovascular ischemic event was an independent
      predictor for risk of recurrence in coagulopathy and control patients.
      CONCLUSIONS: Our observational data do not indicate a significantly increased
      risk for recurrent cerebrovascular events in cryptogenic stroke patients with a
      coagulopathy or any significant influence of the type of antithrombotic
      treatment.

PMID- 19851067
TI  - Retinal vascular abnormalities in patients with cerebral amyloid angiopathy.
AB  - OBJECTIVE: To describe the ophthalmology findings in patients with cerebral
      amyloid angiopathy (CAA). METHODS: Data source and subjects: 7 consecutive
      patients admitted to a tertiary stroke unit with CAA-related hemorrhage,
      confirmed on magnetic resonance brain imaging gradient echo sequences by 2
      independent neuroradiologists. DESIGN: case series. Measurements and data
      analysis: fundus colored photographs and fundus fluorescein angiography. RESULTS:
      All patients showed bilateral multiple dot and blot hemorrhages as well as
      multiple microaneurysms on fundus fluorescein angiography. CONCLUSION:
      Microaneurysms and dot and blot hemorrhages funduscopically mirror the
      histopathology of CAA. This case series is the first to describe retinal vessel
      changes in CAA and, if confirmed in larger population studies, has the potential
      to provide insights into the natural history of CAA.

PMID- 19851068
TI  - Genetic association analysis between TDP-43 polymorphisms and Alzheimer's disease
      in a Japanese population.
AB  - BACKGROUND/AIMS: A recent paper reported that the TAR-DNA binding protein (TDP
      43) is the disease protein in amyotrophic lateral sclerosis and frontotemporal
      lobar dementia with ubiquitin-positive inclusions. In addition, it has been shown
      that TDP-43 may play a role in the pathogenesis of Alzheimer's disease (AD). This
      study aims to investigate whether single nucleotide polymorphisms (SNPs) of the
      TDP-43 gene are associated with AD. METHODS: Eight SNPs, genotyped using TaqMan
      technology, were analyzed using a case-control study design including a haplotype
      analysis. Furthermore, an analysis of the cases divided according to
      apolipoprotein E (APO E) status was also carried out. Our case-control dataset
      consists of 181 AD patients and 130 age-matched controls. RESULTS: Although none
      of the SNPs showed statistically significant association, we identified an
      association between a specific haplotype (G-A-A-G) of the TDP-43 gene and risk
      for AD. We could not confirm any synergetic association between the SNPs and APO
      E in our AD patients. Despite the relatively small sample size, our results
      indicate a possible genetic association between TDP- 43 and AD. CONCLUSION:
      Further genetic studies are needed to clarify the relationship between the TDP-43
      gene and AD.

PMID- 19851069
TI  - Two-layer appearance on brain perfusion SPECT in idiopathic normal pressure
      hydrocephalus: a qualitative analysis by using easy Z-score imaging system, eZIS.
AB  - BACKGROUND/AIMS: It is often difficult to distinguish idiopathic normal pressure
      hydrocephalus (iNPH) from other neurodegenerative disorders such as Alzheimer's
      disease (AD). To understand the characteristic pattern of blood flow in iNPH, we
      performed brain perfusion SPECT and analyzed the results by using the easy Z
      score imaging system (eZIS). METHODS: Subjects were 12 patients with probable
      iNPH and 10 probable AD patients with prominent ventriculomegaly. They underwent
      brain perfusion SPECT using (99m)Tc-ethylcysteinate dimer as a tracer. RESULTS:
      The two-tailed view display in eZIS demonstrated an obvious two-layer structure
      consisting of decreased blood flow around the corpus callosum and, in iNPH,
      enhanced perfusion in areas surrounding the cingulate gyrus in the sagittal view,
      while no AD cases showed these findings. CONCLUSION: Hypoperfusion around the
      corpus callosum in iNPH could be, at least partially, a false-positive finding
      due to an insufficient anatomical standardization of SPECT images caused by an
      abnormally enlarged ventricle. Increased blood perfusion in the external layer
      adjacent to the hypoperfused area might be caused by increased radioisotope count
      per volume resulting from exclusion of cerebral cortex by a dilated ventricle.
      Our results demonstrate that a two-layer appearance revealed by the two-tailed
      view analysis of brain perfusion SPECT using eZIS could be a means to detect
      iNPH.

PMID- 19851070
TI  - Neuropathology and functional deficits in a model of birth asphyxia in the
      precocial spiny mouse (Acomys cahirinus).
AB  - Birth asphyxia can result in sensory impairment, learning and memory deficits
      without gross brain injury and severe motor deficits. We developed a model of
      birth asphyxia resulting in mild neurological injury and cognitive impairment
      using a long-gestation species with precocial fetal development. Spiny mice
      (Acomys cahirinus) underwent caesarean-section delivery or 7.5 min of asphyxia at
      37 days gestational age (term is 39 days). Brain histology was examined at 1 and
      7 days of age, and behaviour was evaluated to 28 days of age. Asphyxiated
      offspring showed significant impairment in non-spatial memory and learning tasks,
      accompanied by central nervous system inflammation and increased apoptotic cell
      death but without the presence of large necrotic or cystic lesions.

PMID- 19851071
TI  - Toll-like receptor-9 agonist inhibits airway inflammation, remodeling and
      hyperreactivity in mice exposed to chronic environmental tobacco smoke and
      allergen.
AB  - BACKGROUND: As passive environmental tobacco smoke (ETS) exposure in nonsmokers
      can increase both asthma symptoms and the frequency of asthma exacerbations, we
      utilized a mouse model, in which ovalbumin (OVA) + ETS induce significantly
      increased levels of eosinophilic airway inflammation and remodeling compared to
      either stimulus alone, to determine whether a Toll-like receptor-9 (TLR-9)
      agonist could reduce levels of airway inflammation, airway remodeling and airway
      hyperreactivity (AHR). METHODS: Mice treated with or without a TLR-9 agonist were
      sensitized to OVA and challenged with OVA + ETS for 1 month. AHR to methacholine
      was assessed in intubated and ventilated mice. Lung Th2 cytokines and TGF-beta(1)
      were measured by ELISA. Lungs were processed for histology and immunohistology to
      quantify eosinophils, mucus, peribronchial fibrosis and smooth muscle changes
      using image analysis. RESULTS: Administration of a TLR-9 agonist to mice
      coexposed to chronic ETS and chronic OVA allergen significantly reduced levels of
      eosinophilic airway inflammation, mucus production, peribronchial fibrosis, the
      thickness of the peribronchial smooth muscle layer, and AHR. The reduced airway
      remodeling in mice treated with the TLR-9 agonist was associated with
      significantly reduced numbers of peribronchial MBP+ and peribronchial TGF
      beta(1)+ cells, and with significantly reduced levels of lung Th2 cytokines
      [interleukin-5 and interleukin-13] and TGF-beta(1). CONCLUSION: These studies
      demonstrate that TLR-9-based therapies inhibit airway inflammation, remodeling
      and AHR in mice coexposed to ETS and allergen who exhibit enhanced airway
      inflammation and remodeling.

PMID- 19851072
TI  - Galectin-9 in allergic airway inflammation and hyper-responsiveness in mice.
AB  - BACKGROUND: Galectin-9 (Gal-9) is a member of the growing family of beta
      galactoside-binding lectins. Gal-9 is an eosinophil chemoattractant and inducer
      of Th1 cell apoptosis. These effects suggest its potential role in the
      pathogenesis of asthma. Our aim was to study the expression of Gal-9 in an
      ovalbumin (OVA)-induced mouse model of allergic asthma. METHODS: To investigate
      the significance of Gal-9 in allergic inflammation and airway hyperresponsiveness
      (AHR), a group of BALB/c mice was sensitized and challenged with OVA (G(OVA)).
      Another group of animals was allergized with OVA and also treated with
      dexamethasone (DEX) (G(OVA+DEX)). The control group (G(PBS)) received phosphate
      buffered saline instead of OVA as placebo. Airway reactivity to intravenous
      methacholine was assessed. RESULTS: The percentage of Gal-9-positive cells and
      their intracellular Gal-9 content and Th1/Th2 cytokine levels in the
      bronchoalveolar lavage (BAL) were determined by flow cytometry. Gal-9 mRNA
      expression and protein level were measured in the lung tissue by real-time RT-PCR
      and Western blot. In G(OVA )mice, airway inflammation and mucus hypersecretion
      developed. DEX treatment inhibited the main features of experimental asthma. The
      number of Gal-9-positive lymphocytes, eosinophil and neutrophil granulocytes and
      the levels of Th2 cytokines were higher in the BAL of G(OVA) compared to G(PBS)
      or G(OVA+DEX )mice. Moreover, Gal-9 protein level was elevated in the lungs of
      G(OVA) mice. CONCLUSIONS: These results suggest that Gal-9 plays a role as a
      mediator contributing to the development of allergic airway inflammation. Gal-9
      may serve as a recruiter of eosinophil granulocytes and promoter of Th2
      dominance.

PMID- 19851073
TI  - Antiapoptotic seminal vesicle protein IV induces histamine release from human
      FcepsilonRI+ cells.
AB  - BACKGROUND: Seminal vesicle protein number 4 (SV-IV) is a small, basic,
      multifunctional, intrinsically disordered secretory protein synthesized in large
      amounts by rat seminal vesicle epithelium under androgen transcriptional control.
      SV-IV-immunorelated proteins occur in other rat tissues and in humans. METHODS:
      The in vitro effect of SV-IV on human FcepsilonRI+ cells was investigated by
      standard immunologic, biochemical and molecular biology procedures. RESULTS: SV
      IV-induced histamine release from human basophils and lung mast cells without any
      influence on leukotriene C(4) release and cell migration. The histamine release
      rate was slower compared with that induced by anti-IgE, the temperature
      dependence of the event being similar. SV-IV-induced histamine release was Ca2+
      dependent, suggesting a physiological interaction of the protein with
      FcepsilonRI+ cells. SV-IV and anti-IgE acted synergistically on the histamine
      release. SV-IV did not induce de novo synthesis of cytokines and growth factors
      (transforming growth factor-beta(1), interleukin-10, interleukin-13, tumor
      necrosis factor-alpha, vascular endothelial growth factor A) in FcepsilonRI+
      cells. CONCLUSIONS: SV-IV protein induces in human FcepsilonRI+ cells the release
      of histamine, a proinflammatory, antiapoptotic and immunosuppressive biogenic
      amine. These data: (1) are consistent with the antiapoptotic and
      immunosuppressive properties of SV-IV; (2) confirm a regulatory feature of SV-IV
      on mammal inflammatory reactivity by either inhibiting the arachidonate cascade
      pathway or stimulating proinflammatory cytokine release from lymphocyte/monocytes
      and histamine from FcepsilonRI+ cells; (3) raise the possibility of a protective
      role of SV-IV on implanting hemiallogenic blastocysts against maternal reactive
      oxygen species and immunological attacks at the uterine implantation site.

PMID- 19851074
TI  - Oral challenge with pasteurized egg white from Gallus domesticus.
AB  - BACKGROUND: Since raw egg may cause digestive toxic infections, we assessed
      whether pasteurized raw egg white is as reliable as fresh raw egg white in the
      diagnosis of egg allergy. METHODS: Thirty-two egg-allergic children were
      challenged with both pasteurized and fresh raw egg white. Open challenges were
      carried out with increasing doses of pasteurized raw egg white and fresh raw egg
      white administered every 60 min. RESULTS: Eleven children (34.4%) had positive
      challenges with pasteurized raw egg white. Twenty-one children (65.62%) who
      tolerated pasteurized raw egg white also had a negative challenge with fresh raw
      egg white. If the challenge with pasteurized raw egg white resulted positive, the
      study was stopped. The protein profile and IgE-binding capacity of both
      pasteurized and fresh egg white were almost identical as observed by SDS-PAGE and
      IgE immunoblotting. In the IgE immunoblotting-inhibition and ImmunoCAP-inhibition
      assays, both extracts behaved in a similar way. CONCLUSIONS: We did not find any
      relevant allergenic differences between fresh and pasteurized egg white. This
      study supports the use of pasteurized egg white in the diagnosis of allergy to
      fresh raw egg proteins.

PMID- 19851075
TI  - Prevalence of food allergy among children in Al-Ain city, United Arab Emirates.
AB  - BACKGROUND: Food allergy (FA) in children is an important health problem.
      However, the prevalence of FA in the United Arab Emirates (UAE) has not yet been
      determined. This cross-sectional study was carried out to assess the prevalence
      of FA among school children aged 6-9 years in Al-Ain city, UAE. METHODS: We used
      multistage random sampling in order to get a sample of 397 school children whose
      parents completed a self-administered questionnaire designed to assess the
      presence or absence of physician diagnosis of FA and other allergic diseases.
      RESULTS: The study showed that the prevalence of physician-diagnosed FA in
      children was 8% (95% CI 5.4-10.8%). Eggs, fruits and fish were the main allergies
      reported. FA was independently related to a family history of FA, to a small
      sibship size and to a personal history of other atopic diseases. CONCLUSIONS: The
      prevalence of FA in Al-Ain city was 8%. A history of FA in first-degree family
      members and a small sibship size were associated with a higher risk of FA in
      children. FA was related to a personal history of other atopic diseases.

PMID- 19851076
TI  - The longest wheal diameter is the optimal measurement for the evaluation of skin
      prick tests.
AB  - BACKGROUND: Mean diameter or longest diameter are the 2 most frequently used
      parameters for wheal response assessment after skin prick testing (SPT). We aimed
      to compare these 2 parameters taking as gold standard the surface of the wheal
      skin response. PATIENTS AND METHODS: Patients suspected of having an allergic
      reaction against inhalant allergens have been skin prick tested using the Pan
      European GA(2)LEN SPT panel. Fifteen minutes later, macroscopically evident wheal
      and flare reactions were marked with a pen and transferred to paper with a
      transparent scotch tape. Each paper-transferred wheal was scanned with an
      ordinary scanner, and its surface-corresponding maximum perpendicular diameters
      and longest diameters were measured using a computer software application for
      image recognition, developed for this purpose. Correlation coefficients
      (Spearman's rho) between surfaces and respective mean (rho(mean)) or longest
      (rho(longest)) diameters were calculated and subsequently compared. RESULTS:
      1,554 SPTs were performed in 74 patients. In 264, a macroscopically evident wheal
      and flare response was observed. Both mean and longest diameters correlated
      significantly with the wheal surfaces. However, rho(longest) was statistically
      significantly larger than rho(mean) when the surface of the wheal was >17 mm(2)
      (rho(longest) > 0.860 vs. rho(mean) < 0.660; p < 0.05).Such a surface corresponds
      to a maximum diameter of approximately 7 mm and a mean diameter of approximately
      6 mm. Thus, the larger the surface of the wheal, the more appropriate the usage
      of the longest diameter. CONCLUSIONS: The longest wheal diameter alone seems to
      be a better surrogate marker of the wheal surface in comparison with the mean
      diameter. In addition, it is easier and faster to measure. Therefore, we propose
      this as the optimal methodology to evaluate SPTs.

PMID- 19851077
TI  - Generation of human inflammation-resistant endothelial progenitor cells by A20
      gene transfer.
AB  - Inflammatory activation of the vascular endothelium is a major contributory
      factor to ischemic cardiovascular disease. Endothelial progenitor cells (EPCs)
      are being investigated for the treatment of ischemic disease or to coat vein
      grafts for bypass surgery. As an inflammatory environment might reduce their
      therapeutic efficacy, we sought to generate EPCs that are less sensitive to
      inflammatory activation. EPCs were obtained from human umbilical cord blood and
      transduced with a lentiviral vector for stable expression of A20, an anti
      inflammatory protein. Nontransduced and green-fluorescent-protein-transduced
      cells were used as controls. Expression of A20 by EPCs did not modify cell
      morphology or expression of a panel of 20 proteins known to contribute to
      angiogenesis. Also, A20 had no effect on the capacity of EPCs to form tube-like
      structures in Matrigel. A20 expression reduced EPC activation by tumor necrosis
      factor-alpha and interleukin-1beta as determined from changes in vascular cell
      adhesion molecule 1 and E-selectin expression and decreased monocyte
      transmigration through a monolayer of EPCs. In conclusion, EPCs can be
      genetically modified to overexpress A20 in a stable fashion. These cells become
      less sensitive to inflammatory stimuli. This may be of interest in cell-based
      therapeutic approaches for clinical settings where inflammation is an important
      pathogenic factor.

PMID- 19851079
TI  - Soluble e-selectin is an inverse and independent predictor of left ventricular
      wall thickness in end-stage renal disease patients.
AB  - BACKGROUND: E-selectin is a specific endothelial cell product involved in
      leukocyte recruitment on the endothelium, which is an important early step in the
      reparative process following vascular damage. In end-stage renal disease (ESRD),
      the relationship of E-selectin with left ventricular function has been so far
      neglected. METHODS: We studied 237 patients on chronic dialysis (200 on
      hemodialysis, 37 on continuous ambulatory peritoneal dialysis) for at least 6
      months, without clinical evidence of heart failure. On a mid-week non-dialysis
      day, fasting blood sampling and echocardiography were performed. RESULTS: Left
      ventricular mass index (LVMI, corrected for height) was inversely related to E
      selectin levels, increasing from 56.8 +/- 18.9 (>75th percentile E-selectin
      tertile) to 66.7 +/- 20.1 g/m(2.7) (<50th percentile E-selectin tertile) (p =
      0.002). However, in multiple regression models, including traditional (age, sex,
      smoking, diabetes, systolic blood pressure, hemoglobin, albumin, previous
      cardiovascular events) and emerging (asymmetric dimethylarginine, interleukin-6)
      risk factors associated with ESRD, soluble E-selectin has proved to be a
      significant inverse and independent predictor of mean wall thickness, but not of
      LVMI. CONCLUSION: This study demonstrates that soluble E-selectin is inversely
      associated with the muscular component of the left ventricle, thereby suggesting
      that the lack of such a reparative factor may be associated with cardiac
      remodeling in ESRD patients.

PMID- 19851080
TI  - Editorial.

PMID- 19851078
TI  - Complex regulation and function of the inflammatory smooth muscle cell phenotype
      in atherosclerosis.
AB  - Vascular smooth muscle cell (SMC) phenotypic modulation plays a key role in
      atherosclerosis and is classically defined as a switch from a 'contractile'
      phenotype to a 'synthetic' phenotype, whereby genes that define the contractile
      SMC phenotype are suppressed and proliferation and/or migratory mechanisms are
      induced. There is also evidence that SMCs may take on a 'proinflammatory'
      phenotype, whereby SMCs secrete cytokines and express cell adhesion molecules,
      e.g. IL-8, IL-6, and VCAM-1, respectively, which may functionally regulate
      monocyte and macrophage adhesion and other processes during atherosclerosis.
      Factors that drive the inflammatory phenotype are not limited to cytokines but
      also include hemodynamic forces imposed on the blood vessel wall and intimate
      interaction of endothelial cells with SMCs, as well as changes in matrix
      composition in the vessel wall. However, it is critical to recognize that our
      understanding of the complex interaction of these multiple signal inputs has only
      recently begun to shed light on mechanisms that regulate the inflammatory SMC
      phenotype, primarily through models that attempt to recreate this environment ex
      vivo. The goal of this review is to summarize our current knowledge in this area
      and identify some of the key unresolved challenges and questions requiring
      further study.

PMID- 19851081
TI  - Acute-onset unilateral psychogenic hearing loss in adults: report of six cases
      and diagnostic pitfalls.
AB  - We encountered 6 rare cases of acute-onset unilateral psychogenic hearing loss in
      adults. All were women in their 20s and 30s. Three cases had severe hearing
      impairment characterized by hearing loss at every frequency; 2 cases had profound
      hearing impairment, and 1 case had low-frequency hearing impairment. Of the 6
      cases, 3 had a history of hearing loss, and 1 had a history of psychogenic visual
      disturbance. All 6 cases were initially diagnosed as having idiopathic sudden
      sensorineural hearing loss; all subsequently received steroid therapy. Three
      cases were not diagnosed as being psychogenic in origin until otoacoustic
      emissions and auditory brain responses were performed. Although the presence of
      distinctive clinical features (age, gender, and past history) is important for
      suspecting psychogenic hearing loss, objective audiological tests such as
      otoacoustic emissions are essential for diagnosing some cases. Compared to the
      existing reports of similar cases, our cases had a poorer prognosis (only 2 cases
      were cured).

PMID- 19851082
TI  - Pharmacokinetic and toxicological profile of artemisinin compounds: an update.
AB  - Artemisinin has been used effectively in malaria treatment. With the emerging
      resistance to malaria, the optimum and judicial use of the drug has become
      important. The drug metabolism and toxicology can have an impact on the
      therapeutic profile and clinical use of this antimalarial agent. In this review,
      we discuss the pharmacokinetics and toxicological aspects of artemisinin and its
      therapeutic implications. Artemisinins have several dosing routes including oral,
      intramuscular, intravenous and rectal. With repeated dosing, artemisinin has
      propensity for autoinduction, leading to decreased plasma levels on repeated
      dosing. Combination with other antimalarials in most cases did not influence the
      pharmacokinetics of artemisinins. Interactions with cytochrome P(450) inhibitors
      are known but these neither affect the efficacy nor the toxicity of the
      respective derivative. Artemisinins are generally regarded to be of low toxicity.
      Two major problems associated with them are neurotoxicity and reproductive
      toxicity. But the extent of this neurotoxicity is dependent on the nature of the
      compound, on the route of administration, and on the nature of the formulation.
      Moreover, it occurs in humans at very high doses. However, as a matter of
      precaution, the use of artemisinins in the first trimester of pregnancy has been
      contraindicated.

PMID- 19851084
TI  - Diagnosis! (not prognosis, not potential, not risk).

PMID- 19851085
TI  - Chondroid syringoma with tyrosine crystals: case report and review of the
      literature.
AB  - Chondroid syringoma (CS) is a relatively rare cutaneous mixed tumor arising from
      sweat glands. It usually presents in the head and neck area as an asymptomatic,
      slow-growing, firm, circumscribed, lobulated nodule within the dermis or
      subcutaneous fat. CSs share morphologic similarities with their salivary gland
      counterparts, pleomorphic adenomas (benign mixed tumors). Although the presence
      of tyrosine-rich crystalloids in mixed tumors of the salivary gland is well
      recognized, to our knowledge, this finding has not been previously described in
      mixed tumors of the skin. We report a case of tyrosine crystalline structures in
      a CS and review the pertinent literature.

PMID- 19851086
TI  - Calcinosis cutis: a rare reaction to subcutaneous injections of calcium
      containing heparin in patients with renal failure.
AB  - Calcinosis of the cutis and the subcutis is a rare complication of calcium
      containing heparin cutaneous injections, mostly occurring in a context of severe
      renal failure. We report 2 cases. The first patient developed firm erythematous
      nodules on his thighs and right arm, in a context of disseminated tuberculosis
      and acute severe renal failure related to human immunodeficiency virus
      nephropathy. Cutaneous location of tuberculosis was suspected. Histological
      features allowed to establish the diagnosis of calcinosis of the cutis and the
      subcutis, showing violaceous and crackled von Kossa-positive calcium deposits in
      the whole reticular dermis and in thin collagenous septa of subcutaneous tissue.
      A retrospective inquiry confirmed that subcutaneous injections of calcium
      containing heparin had been performed on the sites where lesions occurred. The
      second patient developed similar lesions at injection sites of calcium-containing
      heparin, in a context of non-Hodgkin lymphoma and end-stage renal failure.
      Similar histological features were observed. Calcinosis of the cutis and the
      subcutis after subcutaneous injections of calcium-containing heparin is rare. It
      always occurs in a context of elevated calcium-phosphate product, a situation
      mostly encountered in severe renal failure. Early cutaneous lesions do not bear
      specific clinical features.

PMID- 19851087
TI  - Discard volume necessary for elimination of heparin flush effect on
      thromboelastography.
AB  - Heparin is commonly used to prevent obstruction of indwelling arterial catheters
      with blood clots. It is known to affect the outcomes of analysis of coagulation
      parameters with thromboelastography (TEG); therefore, it has been recommended to
      neutralize its effect with heparinase. However, heparinase may also neutralize
      the effect of low molecular weight heparin and endogenous heparinoids present in
      critically ill patients and thus yields unreliable results. The aim of this study
      was to evaluate the minimal discard blood volume needed to eliminate the effect
      of heparin flush on TEG parameters without the use of heparinase. Ten patients
      with indwelling arterial catheter were included in the study. Coagulation
      parameters were evaluated with kaolin-activated TEG. Blood samples were obtained
      after discarding 1, 2, 3, 4, 5 or 10 ml of blood to eliminate the effect of
      heparin. We investigated the influence of the discard volume on time until the
      first detectable clot (R), speed of clot development (alpha angle), maximal
      amplitude of the measured clot and time to maximal amplitude of the measured
      clot. We found an increase in coagulation (reflecting the heparin elimination)
      with the increasing discard volume between 1 and 4 ml. This was obvious from an
      increase in alpha angle and maximal amplitude of the measured clot and a decrease
      in R and time to maximal amplitude of the measured clot (P < 0.001). However,
      values obtained after discarding 4, 5 and 10 ml of blood did not differ markedly.
      To obtain valid information about TEG parameters, it is necessary to discard
      volume of at least 4 ml of blood (i.e., five times the volume of catheter dead
      space).

PMID- 19851088
TI  - Cerebral venous thrombosis initially presenting with left occipital hemorrhage
      and headache.
AB  - Cerebral venous thrombosis (CVT) can be difficult to diagnose because of its wide
      spectrum of clinical manifestations. In the present article, we report a 58-year
      old man coming to our emergency department presenting with left temporal
      throbbing headache and right hemianopia. Computed tomography of the brain
      revealed acute hemorrhages over the left occipital area. Due to the unusual
      location of hemorrhage, magnetic resonance venography was performed, revealing
      absence of venous flow over the superior sagittal and transverse sinuses
      suggestive of CVT. He received anticoagulant therapy for 6 months and the
      headache subsided. We feel that a high index of clinical suspicion is needed to
      diagnose an intracerebral hemorrhage in an uncommon site caused by CVT, even if
      risk factors of CVT are not present, so that appropriate treatment can be
      initiated as promptly as possible. Failure to recognize the signs of CVT could
      result in inappropriate management and suboptimal secondary prophylaxis
      strategies, which could affect the patient's clinical outcome.

PMID- 19851089
TI  - Current insight into thrombotic thrombocytopenic purpura.
AB  - During the last three decades knowledge regarding the pathophysiology of
      thrombotic thrombocytopenic purpura (TTP) has dramatically increased. The
      discovery of ADAMTS13 (a disintegrin-like and metalloproteinase with
      thrombospondin type-1 motifs 13) deficiency in a subset of patients with TTP has
      been an important milestone. Apart from this, the use of therapeutic plasma
      exchange has reduced mortality rates in TTP from 80-90% to 10-20%. Nevertheless,
      TTP remains a possibly lethal disorder, in which early recognition of symptoms
      remains extremely important. In the last few years some interesting new insights
      into TTP have arisen. Firstly, promising reports on rituximab in the treatment of
      refractory and relapsing cases of TTP have been published. Secondly, risk
      stratification by means of ADAMTS13 deficiency and ADAMTS13 antibodies might lead
      to a more tailored approach in treating TTP patients.

PMID- 19851090
TI  - Hydrogen sulfide promotes transient receptor potential vanilloid 1-mediated
      neurogenic inflammation in polymicrobial sepsis.
AB  - OBJECTIVE: To investigate the interaction and involvement of hydrogen sulfide and
      transient receptor potential vanilloid type 1 in the pathogenesis of sepsis.
      Hydrogen sulfide has been demonstrated to be involved in many inflammatory states
      including sepsis. Its contribution in neurogenic inflammation has been suggested
      in normal airways and urinary bladder. However, whether endogenous hydrogen
      sulfide would induce transient receptor potential vanilloid type 1-mediated
      neurogenic inflammation in sepsis remains unknown. DESIGN: Prospective,
      experimental study. SETTING: Research laboratory. SUBJECT: Male Swiss mice.
      INTERVENTIONS: Mice were subjected to cecal ligation and puncture-induced sepsis
      and treated with transient receptor potential vanilloid type 1 antagonist
      capsazepine (15 mg/kg subcutaneous) 30 mins before cecal ligation and puncture.
      To investigate hydrogen sulfide-mediated neurogenic inflammation in sepsis, DL
      propargylglycine (50 mg/kg intraperitoneal), an inhibitor of hydrogen sulfide
      formation was administrated 1 hr before or 1 hr after the induction of sepsis,
      whereas sodium hydrosulfide (10 mg/kg intraperitoneal), a hydrogen sulfide donor,
      was given at the same time as cecal ligation and puncture. Lung and liver
      myeloperoxidase activities, liver cystathionine-gamma-lyase activity, plasma
      hydrogen sulfide level, histopathological examination, and survival studies were
      determined after induction of sepsis. MEASUREMENTS AND MAIN RESULTS: Capsazepine
      treatment attenuates significantly systemic inflammation and multiple organ
      damage caused by sepsis, and protects against sepsis-induced mortality.
      Similarly, administration of sodium hydrosulfide exacerbates but capsazepine
      reverses these deleterious effects. In the presence of DL-propargylglycine,
      capsazepine causes no significant changes to the attenuation of sepsis-associated
      systemic inflammation, multiple organ damage, and mortality. In addition,
      capsazepine has no effect on endogenous generation of hydrogen sulfide,
      suggesting that hydrogen sulfide is located upstream of transient receptor
      potential vanilloid type 1 activation, and may play a critical role in regulating
      the production and release of sensory neuropeptides in sepsis. CONCLUSIONS: The
      present study shows that hydrogen sulfide induces systemic inflammation and
      multiple organ damage characteristic of sepsis via transient receptor potential
      vanilloid type 1-mediated neurogenic inflammation.

PMID- 19851091
TI  - Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and
      oxygenation in lipopolysaccharide-induced lung injury in piglets.
AB  - OBJECTIVE: To study angiotensin-converting enzyme 2 in a piglet model with acute
      respiratory distress syndrome and to evaluate the therapeutic potential of this
      substance in a preclinical setting, as this model allows the assessment of the
      same parameters required for monitoring the disease in human intensive care
      medicine. The acute respiratory distress syndrome is the most severe form of
      acute lung injury with a high mortality rate. As yet, there is no specific
      therapy for improving the clinical outcome. Recently, angiotensin-converting
      enzyme 2, which inactivates angiotensin II, has been shown to ameliorate acute
      lung injury in mice. DESIGN: Prospective, randomized, double-blinded animal
      study. SETTING: Animal research laboratory. SUBJECTS: Fifteen anesthetized and
      mechanically ventilated piglets. INTERVENTIONS: Acute respiratory distress
      syndrome was induced by lipopolysaccharide infusion. Thereafter, six animals were
      assigned randomly into angiotensin-converting enzyme 2 group, whereas another six
      animals served as control. Three animals received angiotensin-converting enzyme 2
      without lipopolysaccharide pretreatment. MEASUREMENTS AND MAIN RESULTS: Systemic
      and pulmonary hemodynamics, blood gas exchange parameters, tumor necrosis factor
      alpha, and angiotensin II levels were examined before acute respiratory distress
      syndrome induction and at various time points after administering angiotensin
      converting enzyme 2 or saline. In addition, ventilation-perfusion distribution of
      the lung tissue was assessed by the multiple inert gas elimination technique.
      Animals treated with angiotensin-converting enzyme 2 maintained significantly
      higher PaO2 than the control group, and pulmonary hypertension was less
      pronounced. Furthermore, angiotensin II and tumor necrosis factor-alpha levels,
      both of which were substantially increased, returned to basal values. Multiple
      inert gas elimination technique revealed a more homogeneous pulmonary blood flow
      after treatment with angiotensin-converting enzyme 2. In intergroup comparisons,
      there were no differences in pulmonary blood flow to lung units with subnormal
      ventilation/perfusion ratios. CONCLUSIONS: Angiotensin-converting enzyme 2
      attenuates arterial hypoxemia, pulmonary hypertension, and redistribution of
      pulmonary blood flow in a piglet model of acute respiratory distress syndrome,
      and may be a promising substance for clinical use.

PMID- 19851093
TI  - Diabetes does not alter mortality or hemostatic and inflammatory responses in
      patients with severe sepsis.
AB  - OBJECTIVE: Diabetes patients have an increased risk of sepsis. Several
      inflammatory and coagulant pathways that are activated during sepsis are also up
      regulated in diabetes patients. We tested our a priori hypothesis that the
      presence of diabetes adversely affects the outcome of sepsis. DESIGN:
      Retrospective analysis of a previously published study. SETTING: Intensive care
      units of 164 centers in 11 countries. PATIENTS: Eight hundred thirty severe
      sepsis patients who were admitted to the intensive care unit and who received
      standard critical care treatment. INTERVENTIONS: Patients were stratified into
      diabetic and nondiabetic patient groups. Mortality was assessed after 28 and 90
      days, causative microorganisms were evaluated, and markers of coagulation,
      fibrinolysis, and inflammation were measured at several time points. MEASUREMENTS
      AND MAIN RESULTS: Diabetes was present in 22.7% of all sepsis patients.
      Throughout the study, plasma glucose levels were higher in diabetic patients.
      Mortality was equal in diabetic and nondiabetic patients (31.4% vs. 30.5% after
      28 days). Markers of coagulation, fibrinolysis, and inflammation were generally
      equal in diabetic and nondiabetic patients, although on admission diabetic
      patients had slightly higher levels of anticoagulation markers. Interestingly,
      nondiabetic patients with admission hyperglycemia (>11.1 mmol/L; 200 mg/dL) had a
      higher mortality rate compared to those without admission hyperglycemia (43.0%
      vs. 27.2%). CONCLUSIONS: Although diabetes is a risk factor for sepsis, once
      established, the outcome of severe sepsis does not appear to be significantly
      influenced by the presence of diabetes. In nondiabetic patients, however,
      admission hyperglycemia is associated with an increased mortality.

PMID- 19851092
TI  - Protective effects of recombinant osteopontin on early brain injury after
      subarachnoid hemorrhage in rats.
AB  - OBJECTIVE: Accumulated evidence suggests that the primary cause of poor outcome
      after subarachnoid hemorrhage is not only cerebral arterial narrowing but also
      early brain injury. Our objective was to determine the effect of recombinant
      osteopontin, a pleiotropic extracellular matrix glycoprotein, on early brain
      injury after subarachnoid hemorrhage in rats. DESIGN: Controlled in vivo
      laboratory study. SETTING: Animal research laboratory. SUBJECTS: One hundred
      seventy-seven male adult Sprague-Dawley rats weighing 300 to 370 g.
      INTERVENTIONS: The endovascular perforation model of subarachnoid hemorrhage was
      produced. Subarachnoid hemorrhage or sham-operated rats were treated with an
      equal volume (1 microL) of pre-subarachnoid hemorrhage intracerebroventricular
      administration of two dosages (0.02 and 0.1 microg) of recombinant osteopontin,
      albumin, or vehicle. Body weight, neurologic scores, brain edema, and blood-brain
      barrier disruption were evaluated, and Western blot analyses were performed to
      determine the effect of recombinant osteopontin on matrix metalloproteinase-9,
      substrates of matrix metalloproteinase-9 (zona occludens-1, laminin), tissue
      inhibitor of matrix metalloproteinase-1, inflammation (interleukin-1beta), and
      nuclear factor-kappaB signaling pathways. MEASUREMENTS AND MAIN RESULTS:
      Treatment with recombinant osteopontin prevented a significant loss in body
      weight, neurologic impairment, brain edema, and blood-brain barrier disruption
      after subarachnoid hemorrhage. These effects were associated with the
      deactivation of nuclear factor-kappaB activity, inhibition of matrix
      metalloproteinase-9 induction, the maintenance of tissue inhibitor of matrix
      metalloproteinase-1, the consequent preservation of the cerebral microvessel
      basal lamina protein laminin, and the tight junction protein zona occludens-1.
      CONCLUSIONS: These results demonstrate that recombinant osteopontin treatment is
      effective for early brain injury after subarachnoid hemorrhage.

PMID- 19851094
TI  - Nutrition therapy in the critical care setting: what is "best achievable"
      practice? An international multicenter observational study.
AB  - OBJECTIVE: To describe current nutrition practices in intensive care units and
      determine "best achievable" practice relative to evidence-based Critical Care
      Nutrition Clinical Practice Guidelines. DESIGN: An international, prospective,
      observational, cohort study conducted January to June 2007. SETTING: One hundred
      fifty-eight adult intensive care units from 20 countries. PATIENTS: Two-thousand
      nine-hundred forty-six consecutively enrolled mechanically ventilated adult
      patients (mean, 18.6 per site) who stayed in the intensive care unit for at least
      72 hrs. INTERVENTIONS: Data on nutrition practices were collected from intensive
      care unit admission to intensive care unit discharge or a maximum of 12 days.
      MEASUREMENTS AND MAIN RESULTS: Relative to recommendations of the Clinical
      Practice Guidelines, we report average, best, and worst site performance on key
      nutrition practices. Adherence to Clinical Practice Guideline recommendations was
      high for some recommendations: use of enteral nutrition in preference to
      parenteral nutrition, glycemic control, lack of utilization of arginine-enriched
      enteral formulas, delivery of hypocaloric parenteral nutrition, and the presence
      of a feeding protocol. However, significant practice gaps were identified for
      other recommendations. Average time to start of enteral nutrition was 46.5 hrs
      (site average range, 8.2-149.1 hrs). The average use of motility agents and small
      bowel feeding in patients who had high gastric residual volumes was 58.7% (site
      average range, 0%-100%) and 14.7% (site average range, 0%-100%), respectively.
      There was poor adherence to recommendations for the use of enteral formulas
      enriched with fish oils, glutamine supplementation, timing of supplemental
      parenteral nutrition, and avoidance of soybean oil-based parenteral lipids.
      Average nutritional adequacy was 59% (site average range, 20.5%-94.4%) for energy
      and 60.3% (site average range, 18.6%-152.5%) for protein. CONCLUSIONS: Despite
      high adherence to some recommendations, large gaps exist between many
      recommendations and actual practice in intensive care units, and consequently
      nutrition therapy is suboptimal. We have identified "best achievable" practice
      that can serve as targets for future quality improvement initiatives.

PMID- 19851095
TI  - Kidney donation from children after cardiac death.
AB  - OBJECTIVE: Pediatric kidney donation after cardiac death is an underutilized
      donor source because of ethical concerns and limited knowledge of the outcome
      after transplantation. The purpose of this study was to report the Dutch
      experience of kidney transplantation using pediatric donation after cardiac
      death. DESIGN: Observational cohort study of a series of consecutive kidney
      transplantations from pediatric donation after cardiac death from January 1995 to
      July 2006. SETTING: Kidneys were procured in seven Dutch procurement areas.
      PATIENTS: Recipients of kidneys from donors after cardiac death aged 2 to 17 yrs.
      MEASUREMENTS AND MAIN RESULTS: Prospectively collected data from the Dutch Organ
      Transplant Registry were analyzed. Donor, graft, and recipient characteristics of
      all pediatric donations after cardiac death kidney transplantations were
      documented. Recipients were followed-up for glomerular filtration rate, graft,
      and patient survival. Eighty-eight patients were transplanted with 90 pediatric
      donation-after-cardiac-death kidneys, which was 31% of the total number of
      transplanted pediatric donor kidneys. In 77% of recipients, organs were procured
      from controlled donors, after withdrawal of supportive treatment. Of all donors,
      9% were younger than age 6 yrs. Two patients received their graft preemptively.
      In the others, the incidence of immediate function, delayed graft function, and
      primary nonfunction were 49%, 44%, and 7%, respectively. Warm ischemia time > or
      =25 mins was associated with primary nonfunction. Overall graft and patient
      survival 5 yrs after transplantation were 80% and 88%, respectively. Graft
      survival after immediate function and delayed graft function was not different.
      CONCLUSIONS: Kidneys from pediatric donation after cardiac death are suitable for
      transplantation and may substantially expand the donor pool with good transplant
      outcome.

PMID- 19851096
TI  - Improving clinical trials in the critically ill.
AB  - OBJECTIVE: To propose ways in which clinical trials in intensive care can be
      improved. METHODS: An international roundtable conference was convened focused on
      improvement in three broad areas: translation of new knowledge from bench to
      bedside; design and conduct of clinical trials; and clinical trial infrastructure
      and environment. RESULTS: The roundtable recommendations were: improvement in
      clinical trials is a multistep process from better preclinical studies to better
      clinical trial methodology; new technologies should be used to improve models of
      critical illness; diseasomes and theragnostics will aid inpatient population
      selection and more appropriate targeting of interventions; broader study end
      points should include morbidity as well as mortality; more multicenter studies
      should be conducted by national and international networks or clinical trials
      groups; and better collaboration is needed with the industry. CONCLUSIONS: There
      was broad agreement among the roundtable participants regarding a number of
      explicit opportunities for the improvement of clinical trials in critical care.

PMID- 19851097
TI  - Increasing intravenous glucose load in the presence of normoglycemia: effect on
      outcome and metabolism in critically ill rabbits.
AB  - OBJECTIVES: Endocrine disturbances and a feeding-resistant wasting syndrome,
      characterized by a negative protein balance, promote delayed recovery and poor
      outcome of critical illness. Parenteral nutrition alone cannot counteract the
      hypercatabolic state, possibly in part as a result of aggravation of the
      hyperglycemic response to illness. In critically ill rabbits, we investigated the
      impact of varying amounts of intravenous glucose while maintaining normoglycemia
      on mortality, organ damage, and markers of catabolism/anabolism. DESIGN:
      Prospective, randomized laboratory investigation. SETTING: University animal and
      molecular laboratory. SUBJECTS: Three-month-old male rabbits. INTERVENTIONS:
      Critically ill rabbits were randomized into a fasting group, a standard
      parenteral nutrition group, and two groups receiving either intermediate or high
      additional physiological amounts of intravenous glucose while maintained
      normoglycemic with insulin. These groups were compared with a hyperglycemic group
      and healthy rabbits. Protein and lipid load was equal for all fed groups.
      MEASUREMENTS AND MAIN RESULTS: Varying intravenous glucose load did not affect
      mortality or organ damage provided hyperglycemia was prevented. Fasted critically
      ill rabbits lost weight, which was attenuated by increasing intravenous glucose
      load. As compared with healthy rabbits, mRNA expression and/or activity of
      several ubiquitin-proteasome pathway components, cathepsin-L and calpain-1, was
      elevated in skeletal muscle of fasted critically ill rabbits. Intravenous feeding
      was able to counteract this response. Excessive glucose load and/or
      hyperglycemia, however, reduced the protective effect of feeding. Genes
      investigated in the diaphragm and myocardium revealed roughly a similar response.
      Except in the normoglycemic group with intermediate glucose load, circulating
      thyroid hormone and insulin-like growth factor-1 levels decreased, most
      pronounced in hyperglycemic rabbits. CONCLUSIONS: Increasing intravenous glucose
      infusion within the physiological range, while maintaining normoglycemia, was
      safe for organ function and survival of critically ill rabbits. Concomitantly, it
      reduced the catabolic responses as compared with fasting. Whether this has a
      beneficial effect on muscle function and mass remains to be investigated.

PMID- 19851098
TI  - Nasal bridling decreases feeding tube dislodgment and may increase caloric intake
      in the surgical intensive care unit: a randomized, controlled trial.
AB  - OBJECTIVE: To determine whether nasal bridling is a low-morbidity practice that
      decreases feeding tube dislodgment and results in improved caloric intake.
      DESIGN: Randomized, controlled trial. SETTING: Private, tertiary-care referral
      center. PATIENTS: A total of 80 surgical intensive care unit patients requiring
      nasojejunal feeding. INTERVENTION: Nasal bridling of feeding tubes. MEASUREMENTS
      AND MAIN RESULTS: Between January 1, 2008 and July 31, 2008, 80 patients were
      randomized to have their nasojejunal feeding tubes secured with either a nasal
      bridle or an adhesive device. Baseline characteristics examined included age,
      sex, concurrent nasogastric tube presence, primary diagnosis, Acute Physiology
      and Chronic Health Evaluation III score, need for mechanical ventilation, need
      for emergent surgery, Riker Sedation Score, and Glascow Coma Scale. Patients were
      monitored daily for prevalence and cause of feeding tube removal, percentage of
      goal calories received, nasal ulceration, and sinusitis. Serum albumin and
      prealbumin levels were collected weekly. All patients were examined, using an
      intention-to-treat design. Except for a higher prevalence of emergent surgery in
      the bridled patients, the bridled and unbridled groups had no difference in
      baseline characteristics. Bridled tubes were less likely to be unintentionally
      dislodged than unbridled tubes (18% vs. 63%, p < .0001) resulting in bridled
      patients receiving a higher percentage of goal calories (median 78%
      [interquartile range, 65%-86%] vs. 62% [interquartile range, 47%-80%], p = .016)
      than unbridled patients. There were five cases of mild epistaxis upon bridle
      insertion and four cases of superficial nasal ulceration associated with the
      bridle. No bridled patients were diagnosed with sinusitis during the study
      period. Serum albumin and prealbumin levels did not differ between the groups.
      CONCLUSIONS: Bridling of nasoenteric feeding tubes in critically ill patients is
      a low-morbidity practice that reduces the rate of unintentional tube dislodgment
      and may result in improved caloric intake.

PMID- 19851099
TI  - Evaluation of nutritional status in older persons: nutritional screening and
      assessment.
AB  - PURPOSE OF REVIEW: Malnutrition is highly prevalent in the older population. It
      is associated with declining functionality and relevant health deficits. This
      review presents the principles of successful nutritional screening and assessment
      in older persons. RECENT FINDINGS: Although no gold standard for the diagnosis of
      malnutrition can serve as reference, a large number of nutritional screening
      tools have been developed during the past two decades. For efficient screening,
      the most appropriate tool has to be selected based on setting and practicability.
      The screening intervals have to be chosen according to the population screened.
      Although screening has to be performed routinely and systematically in a very
      practical and efficient manner, nutritional assessment has to be individualized
      to provide information on the grade of malnutrition and its cause. The
      development of a local guideline that reflects local expertise and resources will
      prove essential for successful nutritional management. CONCLUSION: Nutritional
      screening and assessment should be a standard of care for older persons. It has
      to be considered as a clearly defined two-step procedure, which has to reflect
      setting and local resources. Further adaptations of the available screening tools
      with regard to ethnic characteristics are indicated.

PMID- 19851100
TI  - Antiaging, longevity and calorie restriction.
AB  - PURPOSE OF REVIEW: The role of calorie restriction in humans is controversial.
      Recently, new data in monkeys and humans have provided new insights into the
      potential role of calorie restriction in longevity. RECENT FINDINGS: A study in
      rhesus monkeys showed a reduction in aging-associated mortality. A number of
      controlled studies have suggested a variety of beneficial effects during studies
      of 6-12 months in humans. Major negative effects in humans were loss of muscle
      mass, muscle strength and loss of bone. SUMMARY: Dietary restriction in rodents
      has not been shown to be effective when started in older rodents. Weight loss in
      humans over 60 years of age is associated with increased mortality, hip fracture
      and increased institutionalization. Calorie restriction in older persons should
      be considered experimental and potentially dangerous. Exercise at present appears
      to be a preferable treatment for older persons.

PMID- 19851102
TI  - Financial and intellectual conflicts of interest: confusion and clarity.
AB  - PURPOSE OF REVIEW: To examine the literature on competing interests for
      individuals and organizations involved in healthcare and to determine the nature
      and extent of the problem, and the most effective methods of management. RECENT
      FINDINGS: A Medline search from 1950 to August 2009 identified 6803 publications
      (605 in languages other than English) on the subject of conflict of interest or
      competing interests. Of these, 1073 were letters, 785 editorials, 434 reviews and
      212 referred to competing interests in the context of clinical guidelines.
      Conflicts of interest (competing interests) and bias are ubiquitous. In medicine,
      they may have the potential to cause harm to patients or obstruct research and
      new treatments. Competing interests may arise from financial, academic or
      personal factors. Most interventions relate to managing competing financial
      interests derived from relationships with the pharmaceutical industry. SUMMARY:
      Transparency is a necessary, but not a sufficient component in managing bias.
      Organizations should develop integrated systems for declaring, monitoring and
      managing financial interests; insight into other forms of bias could be improved
      through educational programmes. Marketing masquerading as education should be
      prohibited for undergraduates and trainees, and by professional organizations.
      Universities and journals should separate their conflicted roles as regulators
      and beneficiaries in commercial relationships.

PMID- 19851101
TI  - Organ crosstalk: the role of the kidney.
AB  - PURPOSE OF REVIEW: Acute kidney injury (AKI) continues to contribute
      significantly to morbidity and mortality in the ICU setting, especially when
      associated with distant organ dysfunction. There is increasing evidence that AKI
      directly contributes to organ dysfunction in lung, brain, liver, heart and other
      organs. This review will examine our current understanding of the deleterious
      organ crosstalk in the critically ill, which can provide a framework for
      developing novel therapeutics. RECENT FINDINGS: The majority of studies
      correlating AKI with distant organ dysfunction have demonstrated the
      pathophysiological importance of proinflammatory and proapoptotic pathways as
      well as oxidative stress and reactive oxygen species (ROS) production. Leukocyte
      activation and infiltration, changes in levels of soluble factors such as
      cytokines and chemokines, and regulation of cell death in extra-renal organs are
      potentially important mechanisms by which AKI modulates multiorgan dysfunction.
      SUMMARY: There is increasing knowledge of AKI and deleterious interorgan
      crosstalk that arises, at least in part, due to the imbalance of immune,
      inflammatory, and soluble mediator metabolism that attends severe insults to the
      kidney. Further studies can build on these new mechanistic observations to
      develop strategies to improve outcomes in the critically ill patient.

PMID- 19851103
TI  - Impacts of angiopoietin-like proteins on lipoprotein metabolism and
      cardiovascular events.
AB  - PURPOSE OF REVIEW: Angiopoietin-like proteins (Angptls) comprise a family of
      secreted glycoproteins with high homology to angiopoietins which are important
      regulators of angiogenesis. Angptl3 and Angptl4 inhibit lipoprotein lipase in
      mice. This article reviews recent human studies on Angptls and their effects on
      lipoprotein profiles and cardiovascular disease. RECENT FINDINGS: Population
      based studies have indicated that loss-of-function mutations of Angptl3, Angptl4,
      and Angptl5 are associated with a low triglyceride concentration. Angptl3
      concentration is positively correlated with HDL-cholesterol, but not with
      triglyceride, suggesting that Angptl3 regulates HDL metabolism by inhibiting
      endothelial lipase. Angptl4 concentration is correlated positively with
      triglycerides in patients with metabolic syndrome, although most studies have
      failed to find such a correlation. Angptl6 has no effects on lipoprotein
      profiles. Angptl3 is associated with atherosclerosis in coronary, carotid, and
      femoral arteries. Conflicting results have been obtained regarding whether the
      E40K variant (a loss-of-function mutation of Angptl4) is associated with an
      increased risk for cardiovascular disease, which may occur due to the lipid
      independent actions of Angptl4. SUMMARY: Angptl3, Angptl4, and possibly Angptl5
      are regulators of lipoprotein metabolism in humans. Whether inhibition of these
      Angptls will be useful for dyslipidemia to prevent cardiovascular disease remains
      to be elucidated in future studies.

PMID- 19851104
TI  - The role of flow-mediated dilatation in the evaluation and development of
      antiatherosclerotic drugs.
AB  - PURPOSE OF REVIEW: The present article reviews the use of flow-mediated
      dilatation in clinical cardiovascular research. Its value as a surrogate tool for
      development of antiatherosclerotic drugs and noninvasive assessment of
      cardiovascular risk is also discussed. RECENT FINDINGS: Atherosclerosis remains
      the leading cause of cardiovascular morbidity and mortality. Development of new
      drugs is required to target both the evolution of this disease and its clinical
      consequences. Noninvasive measures of arterial function and structure have been
      widely used as intermediate phenotypes in clinical trials. Numerous studies have
      demonstrated the interplay between vascular risk factors and endothelial function
      as assessed by flow-mediated dilatation in children and adults. Additionally, a
      number of studies have documented the prognostic value of the method. SUMMARY:
      Detection of early arterial changes can prove particularly useful in clinical
      research for the development of antiatherosclerotic drugs. They permit
      identification of vascular toxicity as well as characterization of the safety and
      risk profile of a new cardiovascular treatment modality on vascular health. This
      approach is likely to prove cost-effective before embarking on large longitudinal
      studies to assess cardiovascular morbidity and mortality.

PMID- 19851105
TI  - Intratubular hydrodynamic forces influence tubulointerstitial fibrosis in the
      kidney.
AB  - PURPOSE OF REVIEW: Renal epithelial cells respond to mechanical stimuli with
      immediate transduction events (e.g. activation of ion channels), intermediate
      biological responses (e.g. changes in gene expression), and long-term cellular
      adaptation (e.g. protein expression). Progressive renal disease is characterized
      by disturbed glomerular hydrodynamics that contributes to glomerulosclerosis, but
      how intratubular biomechanical forces contribute to tubulointerstital
      inflammation and fibrosis is poorly understood. RECENT FINDINGS: In-vivo and in
      vitro models of obstructive uropathy demonstrate that tubular stretch induces
      robust expression of transforming growth factor beta-1, activation of tubular
      apoptosis, and induction of nuclear factor-kappaB signaling, which contribute to
      the inflammatory and fibrotic milieu. Nonobstructive structural kidney diseases
      associated with nephron loss follow a course characterized by compensatory
      increases of single nephron glomerular filtration rate and tubular flow rate.
      Resulting increases in tubular fluid shear stress reduce tissue-plasminogen
      activator and urokinase enzymatic activity, which diminishes breakdown of
      extracellular matrix. In models of high dietary Na intake, which increases
      tubular flow, urinary transforming growth factor beta-1 concentrations and renal
      mitogen-activated protein kinase activity are increased. SUMMARY: In conclusion,
      intratubular biomechanical forces, stretch, and fluid shear stress generate
      changes in intracellular signaling and gene expression that contribute to the
      pathobiology of obstructive and nonobstructive kidney disease.

PMID- 19851106
TI  - Obesity hypertension: the emerging role of leptin in renal and cardiovascular
      dyshomeostasis.
AB  - PURPOSE OF REVIEW: Adipose tissue is now considered to be an active physiologic
      system operating in concert with multiple other organs. Leptin is a peptide
      hormone that is primarily synthesized and secreted by adipose tissue whose
      principal action is the control of appetite and energy balance. However, current
      information suggests that leptin exerts pleiotropic effects on several organ
      systems. Herein, we review the potential role of leptin in cardiovascular and
      renal physiological conditions as well as pathophysiological situations including
      obesity and hypertension. RECENT FINDINGS: Increasing evidence suggests that
      leptin may function as a pressure and volume-regulating factor under conditions
      of health; however, in situations characterized by chronic hyperleptinemia such
      as obesity, it may function pathophysiologically for the development of
      hypertension and possibly also for adverse renal, vascular and cardiac
      remodeling. SUMMARY: Adipose tissue should be regarded as a potentially important
      mediator of cardiorenal physiology. Further research awaits the characterization
      of additional mechanisms of action of leptin, including its interface with other
      important endocrine and hemodynamic sodium-volume regulatory systems, in both
      health and disease, particularly in obesity and related comorbidities. This
      information could lead to the development of leptin analogues as well as leptin
      receptor blockers that given specific circumstances could optimize the beneficial
      actions of the hormone and minimize its deleterious effects.

PMID- 19851107
TI  - Clinical management and functional neuromonitoring in traumatic brain injury in
      children.
AB  - PURPOSE OF REVIEW: Traumatic brain injury is the main cause of childhood
      disability and death. In this review, we highlight recent original findings and
      emerging themes from published literature on children with serious traumatic
      brain injury. RECENT FINDINGS: We focus this review on lessons learned from our
      recent randomized clinical trial of hypothermia therapy in severe traumatic brain
      injury in children and on bedside neuromonitoring. We propose that integrating
      the measurement of biomarkers into clinical care as surrogate endpoints and as
      potential prognostic markers would allow us to evaluate earlier the effect of
      injury and clinical care in children after traumatic brain injury. Several
      methods are now more readily available to monitor cerebral physiology in
      children. These methods include indices evaluating the integrity of cerebral
      autoregulation, such as the pressure reactivity index derived from values
      obtained from intracranial pressure measurements, flow velocity measurements from
      transcranial Doppler ultrasonography or from cerebral oximetry. Other methods
      allow the evaluation of coma with the nonlinear analysis of
      electroencephalography or the evaluation of cerebral metabolism and cell death
      pathways with biomarkers from serum, cerebral spinal fluid, and cerebral
      microdialysis. SUMMARY: We suggest expanding clinical functional neuromonitoring
      to help clinicians understand the burden of exposure to physiological variables
      and response to therapies during intensive care in order to enhance the
      management of critically ill children with traumatic brain injury.

PMID- 19851109
TI  - Rheumatic manifestations of systemic disease: sarcoidosis.
AB  - PURPOSE OF REVIEW: Sarcoidosis commonly involves the lungs but also not
      uncommonly presents as uveitis, arthritis, myositis or neurologic disease.
      Recognition of the presenting features, organ complications, and
      immunopathogenesis is important for timely diagnosis and appropriate management.
      RECENT FINDINGS: Current studies support the disorder developing as a consequence
      of a CD4+ T-cell-mediated response to variable environmental or microbial
      triggers in the context of one or more determined susceptibility genes including
      BTNL2, with other genes such as CARD15/NOD2, governing disease severity. Magnetic
      resonance imaging (MRI) is useful in defining the presence and extent of central
      nervous system (CNS), osseous, and both skeletal and cardiac muscle disease.
      Corticosteroids remain the mainstay of therapy; patients with refractory disease
      may respond to other immunomodulating drugs, including anti-TNF-alpha antibodies
      but the optimal roles of traditional immunomodulating as well as newer biologic
      therapies in management are continuing to be defined. SUMMARY: Insights into
      triggering immune events and susceptibility genes should provide potential new
      strategies and targets for therapy. The judicious use of MRI in suspected cases
      can enhance earlier recognition of disease in the CNS, bone, and both skeletal
      and cardiac muscle to guide diagnostic procedures as well as appropriate
      treatment.

PMID- 19851108
TI  - Genetics of food allergy.
AB  - PURPOSE OF REVIEW: Food allergy, a growing clinical and public health problem in
      the United States and worldwide, is likely determined by multiple environmental
      and genetic factors. The purpose of this review is to summarize recent advances
      in food allergy genetic research. RECENT FINDINGS: There is compelling evidence
      that genetic factors may play a role in food allergy. However, the specific
      genetic loci that may modulate individual risk of food allergy remain to be
      identified. To date, only a limited number of candidate gene association studies
      of food allergy have been reported. Polymorphism(s) in nine genes have been
      associated with the incidence of food allergy or food allergy severity in at
      least one study. But most of these findings remain to be replicated in
      independent populations. In contrast, there are considerable advances in genetics
      of other allergic diseases such as asthma and atopic dermatitis. Although asthma
      and atopic dermatitis often coexist with food allergy, the relevance of their
      candidate genes to food allergy remains to be evaluated. SUMMARY: Genetics in
      food allergy is a promising research area but is still in its infancy. More
      studies are needed to dissect susceptible genes of food allergy. A genome-wide
      association approach may serve as a powerful tool to identify novel genes related
      to food allergy. Furthermore, the role of gene-environment interaction, gene-gene
      interaction, and epigenetics in food allergy remains largely unexplored. Given
      the complex nature of food allergy, future studies need to integrate environment,
      genomics, and epigenomics in order to better understand the multifaceted etiology
      and biological mechanisms of food allergy.

PMID- 19851112
TI  - From Survey to Assessment: Characterizing Michigan's Public Health Workforce.
AB  - OBJECTIVE:: To plan for continuity of operations, it is important to know which
      types of position vacancies within health departments are likely to occur and the
      kind of training needed to ensure protection of the public's health. METHODS:: To
      describe anticipated gaps in the public health workforce and to identify specific
      areas of training needed to ensure a highly skilled workforce, the authors
      surveyed Michigan state employees with public health responsibilities in spring
      2007. RESULTS:: More than half (54%) of surveyed public health professionals
      reported they plan to leave the workforce within 10 years. Preparedness-specific
      topics were generally viewed as less important than more general public health
      topics. Some preparedness-funded tools have become integrated into daily
      operations, whereas others were viewed as more important in an everyday, rather
      than emergency preparedness, context. CONCLUSIONS:: Framing preparedness
      activities beyond the scope of preparedness to directly relate them to daily
      public health operations would encourage public health professionals to perceive
      them as more important. For public health preparedness to be fully realized, it
      must be considered a central component of public health operations, allowing for
      seamless integration during emergencies small and large.

PMID- 19851111
TI  - Churg-Strauss syndrome: evidence for disease subtypes?
AB  - PURPOSE OF REVIEW: Churg-Strauss syndrome (CSS) is a rare systemic small-vessel
      necrotizing vasculitis. Its main clinical characteristics, some potentially life
      threatening, are now well known, as are its usual successive phases, from
      allergic rhinitis to asthma, and finally vasculitis. Conversely,
      physiopathogenetic mechanisms are not completely elucidated and clearly multiple,
      thereby suggesting the existence of different disease subtypes. RECENT FINDINGS:
      Almost 40% of CSS patients have circulating antineutrophil cytoplasm
      autoantibodies (ANCAs), mostly directed against myeloperoxidase. ANCA-positive
      patients suffer more frequently from renal disease, peripheral nervous system
      involvement and/or alveolar hemorrhage, whereas frequent cardiac involvement,
      lung infiltrates and/or systemic manifestations are more common in those who are
      ANCA-negative. However, their respective global outcomes do not clearly differ.
      Patients might also be categorized according to other, more subtle clinical,
      radiological and/or biological parameters, for example, cardiac magnetic
      resonance imaging abnormalities or genetic background. SUMMARY: Because of its
      practical and therapeutic repercussions, the priority remains the prompt,
      relatively easy identification of the most severely affected patients at CSS
      diagnosis, before searching for and trying to classify subsets. Large,
      collaborative studies are needed to determine whether other subgroups might be
      associated with outcomes and warrant different, and possibly new, therapeutic
      strategies.

PMID- 19851110
TI  - Rheumatic manifestations of skin disease.
AB  - PURPOSE OF REVIEW: There is an increasing interest in improving the understanding
      of pathophysiology, outcome measures, and therapies of rheumatic skin disease.
      Increasingly, studies are using the skin as a primary endpoint for evaluating
      therapies. This will review the current state of the art for the most common
      rheumatic skin diseases. RECENT FINDINGS: A number of medications, including
      biologics such as tumor necrosis factor alpha and interferon, have been
      associated with onset of cutaneous lupus. The cutaneous lupus erythematosus area
      and severity index has been further validated and utilized in a number of
      studies. Smoking continues to be associated both with presence and refractoriness
      of cutaneous lupus erythematosus to therapy. There are several tools now
      available for evaluating the skin disease of dermatomyositis, but there is a need
      for new effective therapies. Measurement of skin disease in scleroderma continues
      to be a challenge, and there is a need for more effective therapies. Several
      studies show efficacy of intravenous iloprost for severe Raynaud's and skin
      ulcers, and of bosentan for digital ulcers. SUMMARY: The present review covers
      new outcome measures, treatments, and unusual manifestations of cutaneous lupus,
      dermatomyositis, scleroderma, and rheumatoid arthritis. There have been a number
      of new studies related to validation of disease activity measures, as well as
      their use in evaluation of new therapies for these conditions. Validated outcome
      measures are required to perform meaningful studies, and will facilitate
      organized epidemiologic, quality of life, and therapeutic studies.

PMID- 19851113
TI  - Learning fibreoptic intubation with a virtual computer program transfers to
      'hands on' improvement.
AB  - BACKGROUND AND OBJECTIVE: Fibreoptic intubation is an essential skill in
      anaesthesiology that is challenging to learn in the clinical setting. The goal of
      this study was to evaluate 'virtual fibreoptic intubation' (VFI) software as an
      adjunct to the traditional fibreoptic intubation teaching. METHODS: After
      informed consent, 42 undergraduate medical students were randomized into two
      groups. The 'control group' was taught conventionally by an expert bronchoscopist
      with a 1 h lecture. In addition to the didactic lecture by the expert, the 'VFI
      group' was given the VFI CD-ROM, and students self-trained with the software
      until they felt competent performing a virtual fibreoptic bronchoscopy on the
      normal patient models. Students were evaluated 2 weeks later on their first
      orotracheal fibreoptic intubation of an airway manikin. The primary endpoint was
      success, as evaluated by a staff anaesthesiologist blinded to the group of
      teaching. Fibreoptic intubation ability was the secondary endpoint. RESULTS: The
      fibreoptic intubation success rate was significantly higher in the VFI group than
      in the control group (81 versus 52%, P < 0.05). Among 10 failures in the control
      group, nine were due to oesophageal intubation as compared with only one out of
      four in the VFI group. Among four failures in the VFI group, three were because
      of taking longer than 4 min as compared with only one out of 10 in the control
      group. The VFI group tended towards better ability in the procedural skills of
      fibreoptic intubation than the control group. CONCLUSION: Self-training in
      fibreoptic intubation with the VFI software may improve the acquisition of
      fibreoptic intubation skills.

PMID- 19851114
TI  - The use of emergency medical cooling system pads in the treatment of malignant
      hyperthermia.

PMID- 19851115
TI  - Pharmacokinetic interaction of ritonavir-boosted elvitegravir and maraviroc.
AB  - BACKGROUND: The pharmacokinetic (PK) interaction between ritonavir-boosted
      elvitegravir (elvitegravir/r) and maraviroc was evaluated. METHODS: Healthy
      subjects were randomized to receive elvitegravir/r (150/100 mg once daily) before
      or after elvitegravir/r plus maraviroc (150 mg twice daily) (group 1; n = 20) or
      receive maraviroc before or after maraviroc plus elvitegravir/r (group 2; n =
      16). All regimens were administered for 10 days and elvitegravir, ritonavir, and
      maraviroc PK determined. Lack of PK alteration was defined as 90% confidence
      intervals for ratio of geometric least squares means ratio
      (coadministration:alone) between 70% and 143% for elvitegravir and ritonavir Cmax
      (maximum concentration), Ctau (trough), and AUCtau (area under plasma
      concentration-time curve; 0-24 hours); for maraviroc, given a 100% increase in
      Cmax and AUCtau (0-12 hours); the predicted 90% confidence intervals were 162% to
      247% and 136% to 295%, respectively. RESULTS: Twenty-eight of 36 enrolled
      subjects completed the study; one discontinuation was due to an adverse event.
      The most common adverse event across treatments was headache. Upon
      coadministration, elvitegravir and ritonavir PK were unaltered, but maraviroc
      exposures were 2-fold to 4-fold higher presumably due to ritonavir-mediated CYP3A
      /Pgp inhibition. CONCLUSIONS: During elvitegravir/r plus maraviroc
      administration, no elvitegravir or ritonavir dose change and a reduced 150-mg
      dose of maraviroc are recommended.

PMID- 19851116
TI  - Mitral valve repair complicated by iatrogenic coronary artery lesion treated with
      percutaneous coronary intervention.
AB  - We report a case of mitral valve repair complicated by iatrogenic coronary artery
      lesion. This rare coronary injury caused an acute ST-elevation myocardial
      infarction and it was treated successfully with a percutaneous coronary
      intervention.

PMID- 19851117
TI  - Respiratory muscle strength in rheumatic mitral stenosis improves after balloon
      valvotomy.
AB  - BACKGROUND: Dyspnea is a common symptom in a patient with valvular heart disease.
      The mechanism underlying this disease is still uncertain. Respiratory muscle
      weakness has been proposed to be one of the mechanisms underlying dyspnea in
      heart failure, but this has not been adequately studied in valvular heart
      disease. METHODS: We prospectively studied 20 patients with rheumatic mitral
      valve stenosis who were candidates for percutaneous balloon mitral valvotomy.
      Respiratory muscle strength assessment by maximal static inspiratory mouth
      pressure and maximal static expiratory mouth pressure was done on all patients at
      baseline and at 1 week after the procedure. The severity of dyspnea in study
      participants was also studied by the 6-min walk test and visual analog scale.
      RESULTS: Balloon valvotomy was followed by a significant improvement in the 6-min
      walking distance (from 219 +/- 30.15 to 237.55 +/- 32.25 m, P < 0.001), visual
      analog scale as a measure of dyspnea (from 60.95 +/- 12.16 to 44.4 +/- 13.71 mm,
      P < 0.001), inspiratory muscle strength (from 51.9 +/- 10.28 to 56.55 +/- 11.87
      cmH2O, P < 0.001) and expiratory muscle strength (from 62.15 +/- 19.68 to 67.20
      +/- 21.91 cmH2O, P < 0.001). CONCLUSION: Improvement in dyspnea in mitral
      stenosis after balloon valvotomy is associated with significant improvement in
      respiratory muscle strength.

PMID- 19851118
TI  - Comprehensive noninvasive evaluation of bypass grafts and native coronary
      arteries in patients after coronary bypass surgery: accuracy of 64-slice
      multidetector computed tomography compared to invasive coronary angiography.
AB  - AIMS: We assessed the accuracy of 64-slice multidetector computed tomography
      (MDCT) compared with that of invasive coronary angiography (ICA) in the
      evaluation of symptomatic postcoronary artery bypass graft (post-CABG) patients.
      METHODS: MDCT and ICA were performed in 44 consecutive post-CABG patients with
      chest pain (mean age 66 +/- 10 years, mean duration post-CABG 9 +/- 5 years).
      MDCT findings were compared with the corresponding ICA, which was read by an
      interventional cardiologist blinded to the MDCT findings. Significant stenosis
      was defined as at least 50% luminal stenosis. RESULTS: One hundred and thirty
      seven grafts (31 arterial and 106 venous), all evaluable by MDCT, were assessed.
      In a 'per graft' analysis, MDCT could detect significant disease in bypass grafts
      (graft occlusion or stenosis) with a sensitivity of 98% and specificity of 98%.
      In a 'per segment' analysis, MDCT could detect significant disease in all native
      coronary arteries with a sensitivity of 91% and specificity of 79% and in
      clinically relevant native coronary arteries with a sensitivity of 92% and
      specificity of 84%. In a 'per vessel' analysis, MDCT could differentiate native
      arterial occlusion from nonocclusive stenosis with a sensitivity of 68% and
      specificity of 70%. In a 'per patient' analysis, MDCT could detect significant
      disease in bypass grafts or clinically relevant native coronary arteries with a
      sensitivity of 100%, specificity of 40% and accuracy of 93%. CONCLUSION: Sixty
      four-slice MDCT allows evaluation of bypass grafts and native coronary arteries
      in post-CABG patients. Although accurate for detecting bypass graft disease, 64
      slice MDCT has significant limitations when evaluating native arteries in post
      CABG patients.

PMID- 19851119
TI  - The common functional polymorphism -50G>T of the CYP2J2 gene is not associated
      with ischemic coronary and cerebrovascular events in an urban-based sample of
      Swedes.
AB  - BACKGROUND: CYP2J2 is responsible for the production of 5,6 8,9 11,12 and 14,15
      epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. It is
      abundantly expressed in human heart and also present in kidney and vasculature.
      Carriers of a common polymorphism, the CYP2J2 -50G>T, rs890293, have reduced
      expression of CYP2J2 mRNA level in the heart putatively through the interference
      with a binding site for a transcription factor with consequently reduced
      circulating levels of CYP2J2 epoxygenase metabolites in vivo. AIM: The aim of the
      present study was to evaluate the effect of this functional polymorphism on blood
      pressure (BP) levels, hypertension prevalence, and risk of incident
      cardiovascular events in middle-aged Swedes. METHODS: The CYP2J2 polymorphism was
      genotyped in 5740 participants of the cardiovascular cohort of the 'Malmo Diet
      and Cancer' study. The incidence of cardiovascular events (coronary events, n =
      261; ischemic stroke, n = 185) was monitored over 10 years of follow-up. RESULTS:
      In the whole population the polymorphism had no effect on BP and hypertension
      prevalence and no interaction was found between the polymorphism and sex, age or
      body mass index. Before and after adjustment for major cardiovascular risk
      factors, the hazard ratio for incident ischemic stroke and coronary events was
      not significantly different in carriers of different genotypes. CONCLUSIONS: Our
      data do not support a major role for the CYP2J2 -50G>T variant in determining BP
      level and incident ischemic events. Other studies are needed to elucidate if
      other polymorphisms in the same gene could have a role in BP homeostasis or
      incidence of cardiovascular events.

PMID- 19851120
TI  - Selective chloride loading is pressor in the stroke-prone spontaneously
      hypertensive rat despite hydrochlorothiazide-induced natriuresis.
AB  - OBJECTIVE: To test the hypothesis that in the stroke-prone spontaneously
      hypertensive rat (SHRSP), the pressor effect of selective dietary chloride
      loading depends on a positive external sodium balance. METHODS: In 43 male SHRSP
      fed a Japanese style diet containing a low normal amount of NaCl (0.4%), we
      compared the effects on telemetrically measured SBP of hydrochlorothiazide, 25
      mg/kg per day, alone ('TZ', n = 11); hydrochlorothiazide combined with either KCl
      ('KCLTZ', 2%K, n = 10) or KHCO3 ('KBCTZ', 2%K, n = 11) and no hydrochlorothiazide
      ('CTL', n = 11) over a 10-week period starting at 10 weeks of age. RESULTS: With
      either TZ or KBCTZ, SBP did not increase above baseline values. However, KCLTZ
      induced a sustained increase in SBP of 17 mmHg (P < 0.0001), an increase almost
      half of that occurring without hydrochlorothiazide (CTL), 38 mmHg (P < 0.0001).
      Such divergence of blood pressures with KCLTZ and KBCTZ began over the first 3
      days of their administration, even while they induced similarly negative external
      sodium balances, a positive one occurring only in CTL. Body weight increased more
      without, than with, hydrochlorothiazide, but did not differ between KCLTZ and
      KBCTZ. Changes in SBP occurring on day 2 after treatment assignment predicted
      final changes. CONCLUSION: These results demonstrate that in the SHRSP, dietary
      KCl loading can induce a pressor effect despite concomitant hydrochlorothiazide
      induced natriuresis that elicits a negative external sodium balance. The results
      provide evidence that in the SHRSP the pressor effect of selective chloride
      loading does not depend on a positive external sodium balance, but rather on a
      mechanism actuated by chloride per se.

PMID- 19851121
TI  - Advancing quality diabetes education through evidence and innovation.
AB  - Patients with type 2 diabetes crowd emergency rooms; fill medical, surgical, and
      cardiac beds; and now appear in maternal health and pediatric units. Education is
      critical in hospital care of diabetes; however, what level of knowledge exists
      among acute care nurses? A systematic approach was used to examine levels of
      nursing knowledge about diabetes. An innovative and cost-effective structure was
      created to improve the quality of patient care through supporting diabetes
      education.

PMID- 19851123
TI  - Reliability of displayed tidal volume in infants and children during dual
      controlled ventilation.
AB  - OBJECTIVE: Previous studies have shown a significant difference between
      ventilator-measured tidal volume and actual-delivered tidal volume. However,
      these studies used external methods for measurement of compression volume. Our
      objective was to determine whether tidal volume could be accurately measured at
      the expiratory valve of a conventional ventilator using internal computer
      software to compensate for circuit compliance with a dual control mode of
      ventilation. DESIGN: Clinical study during an 8-month period. SETTING: Pediatric
      intensive care unit. PATIENTS: All patients admitted to the pediatric intensive
      care unit during the enrollment period who were mechanically ventilated using the
      Servo I (Maquet, Bridgewater, NJ) were eligible for this study. INTERVENTIONS:
      Patients were ventilated using a dual-control mode of ventilatory support and
      either an infant or adult circuit (with and without circuit compensation).
      MEASUREMENTS AND MAIN RESULTS: Tidal volume measured at the endotracheal tube
      using a pneumotachometer was compared with ventilator-displayed tidal volume.
      Sixty-eight patients were studied between September 2004 and April 2005. Age
      range was 2 days to 18 yrs (median, 23 mos) and weight range was 2.3 kg to 103 kg
      (median, 14.5 kg) with 41 male patients (60%). We found ventilator-displayed
      tidal volume, without circuit compensation, generally overestimates true
      delivered tidal volume and, with circuit compensation, generally underestimates
      true-delivered tidal volume. However, agreement between tidal volume measured at
      the patient's airway and that measured with and without compensation for circuit
      compliance was good. The error in both cases, without and with circuit
      compensation, is relatively greater in infants and small children. CONCLUSIONS:
      There is an underestimation of delivered tidal volume when compensating for
      circuit volume loss measured at the ventilator. There is no improvement in
      measured tidal volume using circuit compensation in small infants and children.

PMID- 19851122
TI  - Controlled trial of nursing interventions to improve health outcomes of older
      African American women with type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes affects one in five African American women older than
      60 years. These women face distinct challenges in managing diabetes self-care.
      Therefore, tailored self-care interventions for this population need to be
      developed and tested. OBJECTIVES: The effectiveness of a tailored, four-visit, in
      home symptom-focused diabetes intervention with and without booster telephone
      calls was compared with an attentional control focused on skills training for
      weight management and diet. METHODS: African American women (n = 180; >55 years
      old, Type 2 diabetes mellitus >1 year, HbA1c >7%) were randomly assigned to the
      intervention or attentional control condition. Half the intervention participants
      were assigned to also receive a telephone-delivered booster intervention.
      Participants were evaluated at baseline and 3, 6, and 9 months. RESULTS: :
      Baseline HbA1 was 8.3 in the intervention group (n = 60), 8.29 in the
      intervention with booster group (n = 55), and 8.44 in the attentional control
      condition (n = 59). HbA1c declined significantly in the whole sample (0.57%) with
      no differences between study arms. Participants in the booster arm decreased
      HbA1c by 0.76%. Symptom distress, perceived quality of life, impact of diabetes,
      and self-care activities also improved significantly for the whole sample with no
      significant differences between study arms. DISCUSSION: Parsimonious
      interventions of four in-person visits yielded clinically significant decreases
      in HbA1c. Although the weight and diet program was intended as an attentional
      control, the positive effects suggest it met a need in this population. Because
      the contents of both the intervention and the attentional control were effective
      despite different approaches, a revised symptom-focused intervention that
      incorporates weight and diet skills training may offer even better results.

PMID- 19851124
TI  - Early microvascular changes in sepsis and severe sepsis.
AB  - Efforts to improve survival from sepsis are focusing increasingly on intervention
      during the earliest stages of this disease. The importance of derangements in
      microvascular flow in patients with established sepsis is well recognized.
      However, little data are available to describe microvascular changes in early
      sepsis. After research ethics committee approval, observational data were
      collected in healthy volunteers and within 6 h of presentation in patients with
      sepsis and severe sepsis. Sidestream dark-field imaging was used to obtain video
      images of the sublingual microcirculation. Cardiac index was measured using the
      noninvasive suprasternal Doppler method. Forty-eight patients and 16 healthy
      volunteers were recruited. Twenty-eight patients were diagnosed with sepsis and
      19 with severe sepsis. Eight patients (17%) did not survive to leave hospital.
      For small vessels (<20 microm), microvascular flow index (P < 0.05),
      heterogeneity index (P < 0.05) and the proportion of perfused vessels (P < 0.05)
      were lower in patients with sepsis and severe sepsis compared with healthy
      volunteers. Perfused vessel density (P < 0.05) was lower in the severe sepsis
      group compared with the sepsis group. The proportion of perfused vessels (P <
      0.01) and MAP (P < 0.05) were lower in nonsurvivors compared with survivors.
      Sepsis results in derangements of microvascular flow, which can be identified in
      the early stages of this disease. These abnormalities are more marked in the most
      severely ill patients. Further research is required to fully characterize the
      effects of sepsis on microvascular function.

PMID- 19851125
TI  - Sphingosine kinase inhibition alleviates endothelial permeability induced by
      thrombin and activated neutrophils.
AB  - Inflammation and microvascular thrombosis are interrelated causes of acute lung
      injury in the systemic inflammatory response syndrome. Neutrophils
      (polymorphonuclear neutrophil [PMN]) and endothelial cells (EC) activated by
      systemic inflammatory response syndrome interact to increase pulmonary vascular
      permeability, but the interactions between PMN and EC are difficult to study.
      Recently, we reported that sphingosine 1-phosphate is a second messenger
      eliciting store-operated calcium entry (SOCE) in response to inflammatory
      agonists in both PMN and EC. Store-operated calcium entry is therefore a target
      mechanism for the therapeutic modulation of inflammatory PMN-EC interactions.
      Here, we isolated, modeled, and studied the effects of pharmacologic SOCE
      inhibition using real-time systems to monitor EC permeability after exposure to
      activated PMN. We created systems to continuously assess permeability of human
      pulmonary artery endothelial cells and human microvascular endothelial cells from
      lung. Endothelial cells show increased permeability after challenge by activated
      PMN. Such permeability increases can be attenuated by exposure of the cocultures
      to sphingosine kinase (SK) inhibitors (SKI-2, N,N-dimethylsphingosine [DMS]) or
      Ca2+ entry inhibitors (Gd3+, MRS-1845). Human microvascular endothelial cells
      from lung pretreated with SKI-2 or DMS showed decreased permeability when later
      exposed to activated PMN. Likewise, when PMNs were activated with thapsigargin
      (TG) in the presence of SKI-2, DMS, Gd, or MRS-1845, their ability to cause EC
      permeability subsequently was reduced. SKI-2 also inhibited the activation of
      human pulmonary artery ECs by thrombin. These studies will provide a firm
      mechanistic foundation for understanding how systemic SOCE inhibition may be used
      to prevent acute lung injury in vivo.

PMID- 19851126
TI  - Efficacy and safety of dopamine versus norepinephrine in the management of septic
      shock.
AB  - The optimum septic shock vasopressor support strategy is currently debated. This
      study was performed to evaluate the efficacy and safety of norepinephrine (NE)
      and dopamine (DA) as the initial vasopressor in septic shock patients who were
      managed with a specific treatment protocol. A prospective, randomized, open
      label, clinical trial was used in a medical intensive care unit comparing DA with
      NE as the initial vasopressor in fluid-resuscitated 252 adult patients with
      septic shock. If the maximum dose of the initial vasopressor was unable to
      maintain the hemodynamic goal, then fixed-dose vasopressin was added to each
      regimen. If additional vasopressor support was needed to achieve the hemodynamic
      goal, then phenylephrine was added. The primary efficacy end point was all-cause
      28-day mortality. Secondary end points included organ dysfunction, hospital and
      intensive care unit length of stay, and safety (primarily occurrence of
      arrhythmias). The 28-day mortality rate was 50% (67/134) with DA as the initial
      vasopressor compared with 43% (51/118) for NE treatment (P = 0.282). There was a
      significantly greater incidence of sinus tachycardia with DA (24.6%; 33/134) than
      NE (5.9%; 7/118) and arrhythmias noted with DA treatment (19.4%; 26/134) compared
      with NE treatment (3.4%; 4/118; P < 0.0001), respectively. Logistic regression
      analysis identified Acute Physiologic and Chronic Health Evaluation II score (P <
      0.0001) and arrhythmia (P < 0.015) as significant predictors of outcome. In this
      protocol-directed vasopressor support strategy for septic shock, DA and NE were
      equally effective as initial agents as judged by 28-day mortality rates. However,
      there were significantly more cardiac arrhythmias with DA treatment. Patients
      receiving DA should be monitored for the development of cardiac arrhythmias
      (NCT00604019).

PMID- 19851127
TI  - Activated protein C attenuates acute lung injury and apoptosis in a hyperoxic
      animal model.
AB  - Evidence suggests that activated protein C (APC) attenuates acute lung injury
      (ALI) through antithrombotic and anti-inflammatory mechanisms. The aim of this
      study was to determine the effects of APC on ALI in adult rats exposed to
      hyperoxic environment. Rats were divided into control, hyperoxia, hyperoxia +
      APC, and APC. Hyperoxia and hyperoxia + APC were exposed to 1, 3, and 5 days of
      hyperoxia. Hyperoxia + APC and APC were injected with APC (5 mg/kg, i.p.) every
      12 h. Control and hyperoxia received isotonic sodium chloride solution injection.
      Measurement of wet to dry ratio and albumin leak demonstrated significant
      improvement in hyperoxia + APC when compared with hyperoxia. Apoptosis, as
      measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      assay, was significantly reduced in hyperoxia + APC when compared with hyperoxia.
      Histological evaluation of lung sections showed significant reduction in
      inflammation, edema, and in the number of marginating neutrophils in hyperoxia +
      APC as compared with hyperoxia. Transcriptional expression of lung inflammatory
      mediators demonstrated a time-dependent surge in the levels TNF-alpha, IL-1beta,
      and IL-6 in response to hyperoxia that was attenuated with APC administration in
      the presence of hyperoxia. In this rat model, APC attenuates lung injury and the
      expression of inflammatory mediators in ALI secondary to hyperoxia.

PMID- 19851128
TI  - Blue nevi and related lesions: a review highlighting atypical and newly described
      variants, distinguishing features and diagnostic pitfalls.
AB  - Blue nevi and related entities are a heterogenous group of congenital and
      acquired melanocytic tumors that includes established entities such as dendritic
      ("common") blue nevus and cellular blue nevus, and their numerous clinical and
      pathologic variants, such as deep penetrating nevus. They share several clinical
      and morphologic features including their blue tinctorial properties, the presence
      of a dermal proliferation of spindle, fusiform or ovoid cells, associated melanin
      pigment (both within the melanocytic tumor cells and also within macrophages) and
      stromal sclerosis and, at least focal positivity for HMB-45 (Gp100). Some
      variants, such as deep penetrating nevus, often show considerable variation in
      nuclear size and shape, and, as a consequence, are at risk of being misdiagnosed
      as melanoma by those unfamiliar with their characteristic morphologic features.
      The so-called malignant blue nevus is a controversial term denoting melanomas
      arising in association with or exhibiting some morphologic similarities to blue
      nevus. There are also lesions that are probably related to blue nevi, such as the
      recently described pigmented epithelioid melanocytoma and the neurocristic
      hamartomas, whose nature, biologic behavior, and relationship to the better
      established entities remains to be clearly established. This review aims to
      present a brief overview of these lesions, highlighting their pathologic
      characteristics, distinguishing features and potential diagnostic pitfalls, with
      particular emphasis on recently described entities, molecular findings,
      controversial areas, and approaches to diagnosis.

PMID- 19851129
TI  - Fluorescence in situ hybridization in the diagnosis of soft tissue neoplasms: a
      review.
AB  - This paper presents an overview of the role of fluorescence in situ hybridization
      (FISH) in the diagnosis of soft tissue neoplasms. Many soft tissue neoplasms
      harbor characteristic translocations or amplification of gene regions, which can
      be assessed by FISH, and can be used to assist in their diagnosis. We discuss the
      major morphologic categories in which FISH has come to be used including high
      grade round cell sarcomas, spindle cell sarcomas, low-grade myxoid neoplasms,
      adipocytic neoplasms, and malignant melanocytic neoplasms on the basis of a
      recent review of soft tissue neoplasms which were analyzed by FISH. We also
      review the molecular alterations (translocations and amplification of gene
      regions), which have come to define many of these diagnostic entities and the
      most effective way to evaluate them with FISH with attention to potential
      pitfalls. Finally, we discuss the advantages and disadvantages of FISH as a
      technique when appraising soft tissue neoplasms.

PMID- 19851131
TI  - Colorectal cancer due to deficiency in DNA mismatch repair function: a review.
AB  - Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome
      attributable to deleterious germline mutations in mismatch repair (MMR) genes.
      The syndrome is typified by early-onset, frequently right-sided colorectal
      cancers (CRCs) with characteristic histologic features and tendency for
      multiplicity and an increased risk for extracolonic tumors at particular sites;
      it accounts for 1% to 5% of CRC. Deficient mismatch repair (dMMR) function
      manifests as immunohistochemically detectable absence of one or more MMR proteins
      and microsatellite instability (MSI). Approximately 15% of sporadic, noninherited
      CRC are characterized by high-level MSI, nearly always owing to transcriptional
      silencing of MLH1; these sporadic and LS cases exhibit considerable phenotypic
      overlap. Identification of CRC with dMMR is desirable to identify LS and because
      MSI status is prognostic and potentially predictive. This review will discuss the
      history of LS, the principles of MMR and MSI, the clinicopathologic features of
      LS-associated and sporadic high-level MSI CRC, the fundamentals of clinical
      testing for dMMR CRC, and the results of the Columbus-area Lynch syndrome study.
      We conclude with our approach to population-based LS screening based on
      institutional experience with nearly 2000 cases.

PMID- 19851130
TI  - Plasmacytoid dendritic cells: physiologic roles and pathologic states.
AB  - Plasmacytoid dendritic cells (PDCs) have perplexed pathologists for decades,
      undergoing multiple adjustments in nomenclature as their lineage and functions
      have been characterized. Although PDCs account for less than 0.1% of peripheral
      blood mononuclear cells, they serve as a principal source of interferon-alpha and
      are also known as interferon-I producing cells (IPCs). Upon activation in vitro,
      they can differentiate into dendritic cells, and recent studies have
      substantiated a potential role in antigen presentation. Thus, PDCs may act as a
      link between innate and adaptive immunity. Normally found in small quantities in
      primary and secondary lymphoid organs, PDCs accumulate in a variety of
      inflammatory conditions, including Kikuchi-Fujimoto lymphadenopathy, hyaline
      vascular Castleman disease, and autoimmune diseases, and in certain malignancies
      such as classical Hodgkin lymphoma and carcinomas. Demonstrating potential for
      neoplastic transformation reflective of varying stages of maturation, clonal
      proliferations range from PDC nodules most commonly associated with chronic
      myelomonocytic leukemia to the rare but highly aggressive malignancy now known as
      blastic plasmacytoid dendritic cell neoplasm (BPDCN). Formerly called blastic
      natural killer cell lymphoma or CD4/CD56 hematodermic neoplasm, BPDCN, unlike
      natural killer cell lymphomas, is not associated with Epstein-Barr virus
      infection and is generally not curable with treatment regimens for non-Hodgkin
      lymphomas. In fact, this entity is no longer considered to be a lymphoma and
      instead represents a unique precursor hematopoietic neoplasm. Acute leukemia
      therapy regimens may lead to sustained clinical remission of BPDCN, with bone
      marrow transplantation in first complete remission potentially curative in adult
      patients.

PMID- 19851132
TI  - Core components of a comprehensive quality assurance program in anatomic
      pathology.
AB  - In this article the core components of a comprehensive quality assurance and
      improvement plan are outlined. Quality anatomic pathology work comes with focus
      on accurate, timely, and complete reports. A commitment to continuous quality
      improvement and a systems approach with a persistent effort helps to achieve this
      end. Departments should have a quality assurance and improvement plan that
      includes a risk assessment of real and potential problems facing the laboratory.
      The plan should also list the individuals responsible for carrying out the
      program with adequate resources, a defined timetable, and annual assessment for
      progress and future directions. Quality assurance monitors should address
      regulatory requirements and be organized by laboratory division (surgical
      pathology, cytology, etc) as well as 5 segments (preanalytic, analytic,
      postanalytic phases of the test cycle, turn-around-time, and customer
      satisfaction). Quality assurance data can also be used to evaluate individual
      pathologists using multiple parameters with peer group comparison.

PMID- 19851133
TI  - Cystic lymphangioma-like adenomatoid tumor of the adrenal gland: Case
      presentation and review of the literature.
AB  - Adenomatoid tumors (AT) are usually found in the genital tract of both sexes.
      They are very rarely located in extragenital sites, and are exceedingly rare in
      the adrenal. AT of the adrenal gland (AT-AG) are nonfunctioning, usually
      discovered incidentally and confused on imaging with other more common adrenal
      neoplasms. The overwhelming majority occur in males. Thirty-four cases have been
      reported so far, more often presenting grossly as solid tumors, rarely as solid
      with cystic areas, and 5 cases were almost entirely cystic. At histology they can
      be either circumscribed or locally infiltrative, and may pose diagnostic
      difficulties when the pathologist relies on morphology alone or is challenged on
      frozen section. On light microscopy the diagnosis may be very difficult if the
      tumor is rich in vacuolated cells, mimicking metastatic signet ring-cell
      adenocarcinoma. Immunophenotyping and/or electron microscopy are paramount in
      helping to ascertain their mesothelial lineage. Lymphangioma is the main
      histologic mimic of solid-cystic and cystic AT-AG, but lymphangioma is
      immunopositive for endothelial markers and negative for cytokeratins and
      mesothelial markers. Ultrastructural analysis has been performed in 10 published
      cases of AT-AG, in all of which the classical microvilli of coelomic type were
      always observed. In brief we report herein the sixth case of cystic lymphangioma
      like AT, which was incidentally discovered during clinical follow-up in a 39-year
      old man undergoing cancer staging and surveillance after surgery. The adrenal
      tumor was 5.5 cm in size and was fully investigated immunohistochemically and
      ultrastructurally. A complete review of the literature is also presented.

PMID- 19851135
TI  - Why do nice people get bad pneumonia? "Be quick or be dead" (Iron Maiden).

PMID- 19851136
TI  - Clinical microvascular monitoring: a bright future without a future?

PMID- 19851137
TI  - When is it time to go? The difficulty of intensive care unit discharge decisions
      at times of high census or admission demand.

PMID- 19851138
TI  - Prolonged mechanical ventilation: pushing the limits of magic in medicine?

PMID- 19851139
TI  - Under pressure ... do not get lost in space.

PMID- 19851140
TI  - Whisper down the lane or a standardized handover?

PMID- 19851141
TI  - To refer or not to refer: how do we answer the question?

PMID- 19851142
TI  - When is simple too simple? Immortal time bias in critical care.

PMID- 19851143
TI  - Pulmonary artery catheter determined right ventricular ejection fraction and
      right ventricular end-diastolic volume: another case of "The Emperor Has No
      Clothes".

PMID- 19851144
TI  - Volume therapy, plasma osmolality, and vasopressin release in septic shock: "Scio
      ne nihil scire" (Socrates).

PMID- 19851146
TI  - Left ventricular function and high-voltage electrical injury.

PMID- 19851147
TI  - Red blood cell transfusion and mortality.

PMID- 19851148
TI  - Steroid use in acute lung injury/acute respiratory distress syndrome: what about
      the acute lung injury from H1N1?

PMID- 19851149
TI  - Predictive models: the angel is in the details.

PMID- 19851151
TI  - Impact of a prevention strategy targeting hand hygiene and catheter care on the
      incidence of catheter-related bloodstream infections.

PMID- 19851153
TI  - Opioid use for chronic low back pain: A prospective, population-based study among
      injured workers in Washington state, 2002-2005.
AB  - OBJECTIVES: To determine (1) the natural history of prescription opioid use, (2)
      the predictors of long-term opioid use, and (3) the association between opioid
      dose and pain and function in a large cohort of workers with recent back
      injuries. METHODS: Prospective cohort of workers with back injuries (N=1883)
      interviewed 18 days (median) and 1 year after claim submission. Detailed pharmacy
      data were obtained from computerized records of paid bills. RESULTS: Forty-two
      percent of workers (781/1843) received an opioid in the year after injury, most
      (694/781, 89%) at or shortly after the first medical visit for the injury. Of
      these, most (410/694, 59%) received opioids only within the first quarter after
      injury, whereas 16% (111/694) received opioids for 4 quarters. Among these long
      term users, total morphine equivalent dose (MED) increased significantly (P<0.01)
      from the first (mean, 2364 mg; standard deviation, 4019 mg) to the fourth (mean,
      3824 mg; standard deviation, 5998 mg) quarter. Improvement by at least 30% in
      pain and function measure scores occurred in only 26% (95% confidence interval
      18%-36%) and 16% (95% confidence interval 10%-25%), respectively, of long-term
      users. Opioid doses increased substantially over time in all but those in whom
      function improved. After adjustment for baseline pain, function, and injury
      severity, the strongest predictor of longer term opioid prescription was total
      MED in the first quarter. Workers receiving at least 40 mg MED per day in the
      first quarter had 6-fold odds of receiving longer-term opioids. DISCUSSIONS: For
      the small group of workers with compensable back injuries who receive opioids
      longer-term (111/1843, 6%), opioid doses increase substantially and only a
      minority shows clinically important improvement in pain and function. The amount
      of prescribed opioid received early after injury strongly predicts long-term use.
      More research is needed to understand clinical decisions to continue or increase
      opioid therapy after back injury.

PMID- 19851154
TI  - Relationship between the curative effects of carbamazepine administration and the
      neurovascular compression volume of the trigeminal nerve measured using magnetic
      resonance cisternography.
AB  - OBJECTIVES: To elucidate the relationship between the extent of pain and
      neurovascular compression (NVC) volume, measured by magnetic resonance (MR)
      cisternography, in patients with trigeminal neuralgia. In addition, we aimed to
      evaluate the relationship between NVC volume and the efficacy of carbamazepine
      administration in patients with trigeminal neuralgia. METHODS: MR cisternography
      was performed on 214 patients with clinical signs and symptoms that suggested
      trigeminal neuralgia retrospectively. The extent of their pain was evaluated
      using visual analog scales. Next, only carbamazepine was administered as the
      initial treatment. For the patients with NVC detectable on MR cisternography, the
      relationship between the extent or nature of the pain and the neurovascular
      volume was analyzed. In addition, the correlation between the efficacy of
      carbamazepine treatment and the NVC volume was evaluated retrospectively.
      RESULTS: Of the 214 patients evaluated, 144 were deemed to have NVC. In these 144
      patients, a significant difference was found between the NVC volume and the
      curative effects of 100 mg/d carbamazepine. However, no significant correlation
      was found between the extents of pain by visual analog score or between the daily
      dosage of carbamazepine and the NVC volume measured by MR cisternography.
      CONCLUSIONS: Three-dimensional MR cisternography is very useful for detecting the
      site of NVC in patients with trigeminal neuralgia. NVC measured by this technique
      may indicate the prognosis after initial treatment. The present results suggest
      that the evaluation of NVC volume by MR cisternography would be useful in
      choosing the initial treatment for patients with trigeminal neuralgia.

PMID- 19851155
TI  - Flexion-relaxation and clinical features associated with chronic low back pain: A
      comparison of different methods of quantifying flexion-relaxation.
AB  - OBJECTIVES: The purpose of this study was to simultaneously assess 5 surface
      electromyography (SEMG) ratios commonly used to quantify the flexion relaxation
      phenomenon in chronic low back pain patients relative to clinical and
      musculoskeletal abnormalities. METHODS: Seventy-six persons with low back pain
      (LBP) were assessed through SEMG in standing, flexion, maximum voluntary flexion,
      and extension. Additionally, participants were assessed for clinical status (pain
      intensity, perceived disability, and pain-related fear) and musculoskeletal
      abnormalities (supine straight leg raise, Faber test, and lumbar restrictions).
      RESULTS: Flexion-relaxation assessed as the ratio of maximum SEMG during flexion
      to average SEMG during maximum voluntary flexion, and maximum SEMG during
      extension to average SEMG during maximum voluntary flexion, demonstrated that
      highest associations with clinical and musculoskeletal status. Ratio of maximum
      SEMG during flexion to average SEMG during maximum voluntary flexion was
      significantly associated with 2 measures of perceived disability (both rs=-0.31,
      P<0.01), pain-related fear (r=-0.45, P<0.001), as well as range of motion during
      flexion (r=0.51, P<0.001), and elicitation of pain during straight leg raise
      (r=0.30, P<0.05). Ratio of maximum SEMG during extension to average SEMG during
      maximum voluntary flexion was also significantly associated with these same
      measures, at a slightly higher magnitude, in addition to a measure of clinical
      pain (r=-0.29, P<0.05). DISCUSSIONS: These data suggest that measures of flexion
      relaxation that contrast SEMG during flexion or extension to MVF are more highly
      associated with clinical status compared with measures that contrast SEMG during
      flexion and extension, SEMG whereas standing to MVF, or SEMG during MVF alone.

PMID- 19851156
TI  - Correlates of pain intensity in men and women with hip and knee osteoarthritis.
      Results of a national survey: The French ARTHRIX study.
AB  - AIMS OF THE STUDY: To examine the clinical and demographic correlates of pain
      intensity in patients with hip and knee osteoarthritis (OA). PATIENTS AND
      METHODS: In a national cross-sectional survey, 1811 general practitioners
      recruited and assessed 5324 patients with hip and knee OA. The patients rated the
      intensity of pain at rest, on movement over the last 24 hours, and during the
      last 8 days on 11-point numeric rating scales. The patients also completed the
      Western Ontario and McMaster Universities Osteoarthritis Index. Clinical and
      demographic correlates of pain intensity and function were investigated by
      univariate, stepwise multiple logistic regression and odds ratio analyses.
      RESULTS: Data for 4598 patients were analyzed (86.4% of surveyed patients). The
      mean pain intensity was 4.1+/-2.2 at rest, 5.9+/-1.8 on movement during the last
      24 hours, and 5.1+/-1.7 during the last 8 days. Pain on movement during the last
      24 hours and during the last 8 days showed a strong positive correlation (r=0.78;
      P<0.0001), which suggests that the most of the latter pain was related to
      movement. Patients with knee or hip OA did not differ in pain intensity, but
      patients with both joints affected rated pain intensity significantly higher than
      did those with only 1 affected joint [4.6+/-2.1, 6.3+/-1.8, and 5.5+/-1.6, for
      the 3 pain assessments, respectively (P>0.01)]. Patients with high pain ratings
      were more likely to be women, be older than 75 years, and have a body mass index
      of greater than 40 kg/m. In addition, patients who were retired, unemployed,
      farmers, or widowed, or had a long duration of OA gave high pain ratings.
      Patients with regular physical activities reported less intense pain.
      CONCLUSIONS: Pain intensity ratings for patients with lower limb OA differed
      significantly with respect to sex, age, body mass index, physical activity,
      professional activity, marital status, and conditions of assessment.

PMID- 19851157
TI  - Effects of intensity of Transcutaneous Electrical Nerve Stimulation (TENS) on
      pressure pain threshold and blood pressure in healthy humans: A randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVES: Transcutaneous electrical nerve stimulation (TENS) is primarily used
      for pain relief. However, evidence is beginning to emerge that TENS may also have
      a lowering effect on systemic blood pressure (BP). The purpose of this study was
      to investigate the comparative effects of 2 intensities on pressure pain
      threshold (PPT) and resting BP in healthy humans, using low-frequency stimulation
      applied segmentally to the pain site. METHODS: In a double-blind design, 40
      volunteers, stratified by sex, were randomly allocated to 4 groups: high
      intensity ("to tolerance without pain"), low-intensity ("strong but
      comfortable"), placebo, and control. TENS (2 Hz, 250 mu) was applied over the
      distribution of the superficial radial nerve of the dominant hand for 30 minutes.
      The outcome variables were measured at baseline and at 6 subsequent 10-minute
      intervals. For the PPTs, 2 measurements were taken bilaterally from the first
      dorsal interosseous muscle using a pressure algometer. The BP was measured in the
      brachial artery with an automatic monitor. Data difference scores were analyzed
      using repeated-measures and 1-way analyses of variance. RESULTS: The high
      intensity group showed a significant rise in PPT compared with the low-intensity,
      placebo, and control groups for both measurement sites, which sustained 30
      minutes poststimulation. TENS produced no significant effect on BP, regardless of
      intensity. DISCUSSION: These results affirm that high levels of intensity are of
      fundamental importance in effective TENS dosage. This also applies for low
      frequency, segmental stimulation. Resting BP seems not to be dependent on
      intensity.

PMID- 19851158
TI  - Cross-sectional assessment of the consequences of a GTP cyclohydrolase 1
      haplotype for specialized tertiary outpatient pain care.
AB  - OBJECTIVES: Reduced-function variants of the guanosine triphosphate
      cyclohydrolase gene (GCH1) have been associated with reduced pain in well-defined
      cohorts of patients and healthy volunteers. We addressed the question whether
      this genetic association plays a role in outpatient pain therapy. METHODS: In a
      cross-sectional observational study, 523 patients were enrolled in 3 different
      tertiary care outpatient pain centers at German University hospitals. Of the 519
      Caucasian patients, data from 424 could be analyzed for functional associations
      of the formerly named "pain-protective" GCH1 haplotype with the key
      characteristics of pain therapy being (1) actual pain, (2) opioid dosing, and (3)
      pain therapy duration. RESULTS: With an allelic frequency of 14.2% the pain
      protective haplotype was not rarer among pain patients than in the general
      population (P=0.344). However, a tendency toward gene dose-dependent effects of
      the GCH1 haplotype was observed in all the 3 therapy parameters. Carriers of the
      haplotype tended to have lower actual 24-hour pain scores (n=424; P=0.18),
      require lower opioid doses (P=0.096), and were significantly shorter on
      specialized pain therapy (P=0.004). The latter applied predominantly to
      differences between homozygous carriers and heterozygous (alpha-corrected t test:
      P=0.06) or non-carriers (P=0.011) of the haplotype. CONCLUSIONS: The results
      strength the support for a modest yet reproducible and consistent pain-protective
      effect associated with a GCH1 haplotype known to reduce GCH1 and thus BH4 up
      regulation. Pending independent verification, the results might point to a
      prophylactic role of decreased GCH1 up-regulation delaying the need for pain
      therapy.

PMID- 19851159
TI  - A comparison of the effectiveness of landmark-guided injections and
      ultrasonography guided injections for shoulder pain.
AB  - AIM: To compare the effectiveness of landmark-guided local injections and
      ultrasonography (USG) guided injections for shoulder pain. METHODS: A total 60
      consecutive patients with shoulder pain due to soft tissue disorders was
      enrolled, and randomly assigned to receive triamcinolone (40 mg) either by
      landmark-guided (LMG, n=30) or USG guided (n=30) injection. The patients were
      evaluated on admission and 6 weeks after the injection. Clinical assessment
      included demographic and clinical data, a visual analoge scale (VAS) for pain (0
      to 10 cm), the Constant scale (0 to 100) for function, passive and active
      shoulder range of motion (ROM) with goniometric evaluation, and postinjection
      adverse effects. RESULTS: Initial demographic, clinical and USG findings in the
      groups exhibited no significant differences. Six weeks after injection, the VAS
      and the Constant score showed a significantly better improvement in USG group
      compared with LMG group (mean VAS score decrease: 4.0+/-1.7 for USG vs. 2.2+/-0.9
      for LMG, P<0.05; mean Constant score change: 32.2 for USG vs. 12.2 for LMG,
      P<0.05). Significant improvements were observed in active and passive ROM values
      in both groups, USG group values being better. Initially 18 patients in LMG and
      24 patients in USG had limited shoulder ROM, of which 6 was returned to normal
      values in LMG group and 12 in USG group at 6 week after injection (P<0.05).
      CONCLUSIONS: Our results indicate that the injection of corticosteroids to
      patients with shoulder pain due to soft tissue disorders under the USG-guidance
      may improve therapeutic effectiveness and reduce adverse effects.

PMID- 19851160
TI  - A randomized controlled trial of the ShotBlocker for children's immunization
      distress.
AB  - OBJECTIVES: Vaccinations protect children against deadly diseases and
      approximately 30 immunizations are recommended for children by 6 years of age.
      However, immunization injections cause negative short-term and long-term
      consequences for children. The Gate Control Theory of pain suggests that physical
      interventions (eg, rubbing the site) may be helpful, but they are not well
      validated for children's acute pain. This randomized trial examined the
      effectiveness of the ShotBlocker, a physical intervention designed to decrease
      children's injection pain. METHODS: Participants included 89 4- to 12-year-old
      children receiving immunizations at a pediatric practice. Participants were
      randomized to ShotBlocker, placebo control, or typical care control groups.
      Measures of child distress included self-report, parent report, healthcare
      provider report, change in heart rate, and observational behavioral coding.
      RESULTS: No group differences were evident on any of the measures of child pain
      or anxiety when controlling for child age, nor were there any significant
      interactions of treatment condition with child age. On the observational distress
      measure, analysis of covariances revealed significantly higher distress in the
      injection than preinjection or postinjection phases, and postinjection distress
      was higher than preinjection phase distress, irrespective of treatment condition.
      DISCUSSION: The data do not support the effectiveness of the ShotBlocker for
      acute pediatric pain relief. Clinical and theoretical implications are discussed.

PMID- 19851161
TI  - Enriched enrollment randomized withdrawal trial designs of analgesics: focus on
      methodology.
AB  - OBJECTIVES: To systematically identify and critically assess clinical trials that
      use enriched enrollment randomized withdrawal (EERW) trial design as a
      methodology for assessing the effect of analgesics pain. METHODS: A comprehensive
      literature search was conducted through April 2007 in Medline and Embase to
      identify all randomized controlled trials that use EERW trial designs. Data were
      collected from relevant trials and tabulated. Results were categorized on the
      basis of study designs, preenrichment and postenrichment disposition,
      discontinuation rates, primary and secondary efficacy results, and respective P
      values. RESULTS: The literature search identified 2875 unique citations, most of
      which were deemed inappropriate for this analysis. The primary reasons for
      exclusion included inappropriate study design, no available abstract, not a
      clinical study, and therapeutic area not related to chronic pain. Eight EERW
      clinical trials of analgesics were identified. Half of the trials were in chronic
      low back pain, and 5 of 8 trials used an opioid as the active drug. Of the 8
      trials, 5 used a parallel design and 3 used crossover designs. The primary
      efficacy parameter used was pain scores or time to discontinuation, and
      statistically and clinically significant effects in active treatments relative to
      placebo were observed after randomization in all trials. The median magnitude of
      effect was 1.7 on a 10-point scale. Time to exit was a more statistically
      powerful endpoint than mean pain intensity. DISCUSSIONS: EERW trials are an
      emerging type of study design that in certain settings may offer advantages over
      traditional trial designs in characterizing the effects of analgesic medications.

PMID- 19851162
TI  - The successful use of intralipid for treatment of local anesthetic-induced
      central nervous system toxicity: Some considerations for administration of
      intralipid in an emergency.
AB  - Intralipid has been proposed as a treatment option for local anesthetic (LA)
      toxicity, which does not respond to traditional resuscitation methods. This paper
      presents a case report of a patient who developed signs of local anesthetic
      toxicity and was subsequently treated with 20% Intralipid with a positive
      response. Some background and practical applications regarding this treatment are
      discussed.

PMID- 19851164
TI  - The effectiveness of virtual reality on reducing pain and anxiety in burn injury
      patients: a systematic review.
AB  - OBJECTIVE: To systematically review the current evidence for the effectiveness of
      Virtual Reality (VR), in conjunction with pharmacologic analgesia on reducing
      pain and anxiety in burn injury patients undergoing wound dressing changes and
      physiotherapy management compared with pharmacologic analgesia alone or other
      forms of distraction. METHODS: A comprehensive search was conducted between
      December 2007 and January 2008, and updated in January 2009, before publication.
      Computerized bibliographic databases were individually searched using
      specifically developed search strategies to identify eligible studies. RESULTS:
      Nine studies were deemed eligible for inclusion in this review. Wound dressing
      changes was the most common procedure during which VR was trialed. Pain was the
      primary outcome measure in all of the studies included. Anxiety was a secondary
      outcome measure in 3 of the 9 included studies. VR, in conjunction with
      pharmacologic analgesics, significantly reduced pain experienced by burn injury
      patients during wound dressing changes and physiotherapy. There is equivocal
      evidence for the effect of VR in conjunction with pharmacologic analgesics on
      reducing anxiety in burn injury patients during wound dressing changes and
      physiotherapy. DISCUSSION: This is the first known systematic review to report on
      the effectiveness of VR, in conjunction with pharmacologic analgesia on reducing
      pain and anxiety in burn injury patients undergoing wound dressing changes and
      physiotherapy management compared with pharmacologic analgesia alone or other
      forms of distraction. Used as an adjunct to the current burn pain management
      regimens, VR could possibly assist health professionals in making the
      rehabilitation process for burn patients less excruciating, thereby improving
      functional outcomes. Further research investigating the effect of VR on anxiety
      in burn injury patients is warranted.

PMID- 19851163
TI  - Changes in hippocampal metabolites after effective treatment for fibromyalgia: a
      case study.
AB  - BACKGROUND: Fibromyalgia has been associated with disrupted hippocampal brain
      metabolite ratios by studies using single voxel magnetic resonance spectroscopy
      (1H-MRS). Exposure to stress is considered a risk factor for the development and
      exacerbation of fibromyalgia symptoms. Basic science has demonstrated the
      hippocampus to be exquisitely sensitive to the effects of stressful experience,
      which results in changes including alterations in metabolite content and frank
      atrophy. METHODS: This report details the case of a 47-year-old woman with
      fibromyalgia who was originally found to have a profound depression of the ratio
      of N-acetylaspartate to creatine in her right hippocampus during participation in
      a study to assess brain metabolite disturbances in fibromyalgia utilizing single
      voxel proton magnetic resonance spectroscopy. An individualized treatment
      strategy was developed based both on physiological abnormalities associated with
      the disorder and symptoms that characterized the patient's unique clinical
      profile. RESULTS: Clinical and spectroscopic evaluation following nine months of
      treatment demonstrated both an improvement in her clinical profile and
      normalization of the NAA/Cr ratio within her right hippocampus. DISCUSSION:
      Therapeutic strategies aimed at demonstrable lesions associated with fibromyalgia
      appear to represent rational targets for pharmacological intervention. The
      rationale for development of novel pharmacotherapies for this unusual disorder is
      discussed.

PMID- 19851165
TI  - Effects of breastfeeding on pain relief in full-term newborns.
AB  - Breastfeeding may be useful for relieving procedural pain experienced by
      neonates. Researchers have compared breastfeeding against other pain relieving
      approaches in several studies, presenting marked methodologic heterogeneity.
      OBJECTIVE: To investigate the effectiveness of breastfeeding in reducing pain in
      newborns undergoing blood collection for newborn screening. METHOD: The sample of
      this randomized clinical trial study consisted of 60 full-term newborns: 31 in
      the experimental group and 29 in the control group. The experimental group was
      breastfed 5 minutes before, during, and for 5 minutes after the blood collection
      procedure. Neonates in the control group were held in mothers' arms but not fed
      or given a soother. The duration of breastfeeding was prolonged in comparison to
      previous studies. RESULTS: The primary outcomes were Neonatal Facial Actions
      (Neonatal Facial Activity Coding System-upper face), sleep-wake state. Heart rate
      was considered as an index of arousal. Sucking frequency was only evaluated in
      the experimental group. Compared with the control group, the experimental group
      had significantly lower, Neonatal Facial Activity Coding System and sleep-wake
      state scores and heart rates changes. In the experimental group sucking frequency
      was highest during the first 5 minutes of breastfeeding before the procedure.
      DISCUSSION: This study innovates from earlier studies in 4 respects: the
      different phases of the procedure were evaluated separately; the breastfeeding
      intervention covered the period from 5 minutes before the blood collection until
      the end of recovery; sleep-wake state was fully assessed (not merely crying) and
      the sucking frequency in the experimental group was assessed during the
      procedure. The conclusion was that breastfeeding was effective in reducing pain
      caused by blood collection for newborn screening.

PMID- 19851166
TI  - A comparison between diagnostic I-123 and posttherapy I-131 scans in the
      detection of remnant and locoregional thyroid disease.
AB  - AIM OF STUDY: The aim of this study was to compare pretherapy diagnostic I-123
      scans with 7-day posttherapy I-131 scans days in detecting remnant thyroid
      disease as well as locoregional metastases in patients who had undergone
      thyroidectomy for differentiated thyroid cancer. METHODS: The I-123 and I-131
      scans from 53 patients were reviewed. The number of lesions identified on each
      scan was compared as well as the relative intensity of each lesion on the I-123
      and I-131 scans using region-of-interest-derived lesion to background ratios. For
      the I-123 diagnostic scans, 1.0 to 1.6 mCi of activity was administered orally 24
      hours before scan acquisition. Patients received therapeutic doses of I-131
      ranging from 30.7 to 362.2 mCi orally, on the same day but after acquisition of
      the I-123 scan. All posttherapy I-131 scans were performed 7 days after
      radioablative therapy with I-131. RESULTS: Of the 53 patients, 14 had concordant
      scans, with an equal number of lesions detected by both scans. Thirty-nine I
      123/I-131 scan pairs showed discordance, with 27 patients demonstrating more
      lesions on the I-123 scans. Of the 142 total lesions, 35% were detected only by I
      123 pretherapy images compared with 15% detected only on posttherapy images. In a
      subgroup of 42 patients I-123 scans showed 56 lesions (out of a total of 116)
      that demonstrated either a better lesion to background ratio than I-131 or were
      seen exclusively by I-123. CONCLUSION: The use of diagnostic I-123 pretherapy
      scintigraphy seems to be superior in many patients to posttherapy I-131 imaging
      obtained at 7 days in detecting locoregional metastases or remnant in
      postsurgical patients. This is likely due to the fact that 1 week is too long to
      wait to perform posttherapy imaging.

PMID- 19851167
TI  - Evaluation of disease activity using F-18 FDG PET-CT in patients with Takayasu
      arteritis.
AB  - PURPOSE OF THE REPORT: To evaluate the usefulness of F-18 fluoro
      fluorodeoxygulose positron emission tomography computed tomography (F-18 FDG PET
      CT) in detecting clinically defined active disease in patients with Takayasu
      arteritis. METHODS: F-18 FDG PET-CT was performed in 32 patients with Takayasu
      arteritis. Disease activity was assessed clinically by the National Institutes of
      Health (NIH) criteria. In 10 of the 32 patients, F-18 FDG PET-CT was performed
      while the patients were taking immunosuppressive drugs. Two nuclear physicians
      visually assessed the degree of F-18 FDG uptake in the walls of the aorta, its
      major branches and the pulmonary artery using a 4-point scale from grade 0 to
      III. F-18 FDG uptake greater than grade I in the thoracic aorta or greater than
      grade 0 in other areas were interpreted as active vasculitic lesions. RESULTS:
      Ten patients had active lesions on F-18 FDG PET-CT. According to the NIH
      criteria, 9 patients had active disease and 23 had inactive disease. Compared
      with disease activity assessed by the NIH criteria, F-18 FDG PET-CT had a
      sensitivity of 78% and a specificity of 87%. The erythrocyte sedimentation rate
      and CRP levels were significantly higher in F-18 FDG PET-CT-positive than in F-18
      FDG PET-CT-negative patients. There was no significant difference in the
      proportion of positive PET scans according to the use of glucocorticoids.
      CONCLUSIONS: The sensitivity of F-18 FDG PET-CT for detecting active disease was
      higher in patients with higher erythrocyte sedimentation rate values. Although
      the specificity of F-18 FDG PET-CT was high, owing to the low sensitivity of the
      NIH criteria in detecting active disease, further studies are needed.

PMID- 19851168
TI  - Acute coronary syndrome caused by coronary artery mycotic aneurysm due to late
      stent infection localized with radiolabeled autologous leukocyte imaging.
AB  - Mycotic coronary artery aneurysm presenting as acute coronary syndrome is an
      uncommon but fatal condition. The diagnosis of mycotic aneurysm can be very
      challenging and difficult. Therefore, a high index of suspicion along with the
      use of multimodality imaging may help to diagnose this condition in patients with
      a prior history of coronary artery bypass grafting or percutaneous coronary
      intervention with persistent bacteremia with no identifiable source of infection.
      This case highlights a possibility of late stent infection and its association to
      drug eluting stents.

PMID- 19851169
TI  - F-18 FDG-PET/CT evaluation of patients with differentiated thyroid cancer with
      negative I-131 total body scan and high thyroglobulin level.
AB  - PURPOSE: The aim was to evaluate the incremental diagnostic rate of F-18 fluoro
      fluorodeoxygulose positron emission tomography/computed tomography (F-18 FDG
      PET/CT) in patients with negative I-131 whole body scans and high Tg levels. The
      secondary end points were correlations between F-18 FDG-PET/CT positive results
      and Tg levels and comparison between F-18 FDG-PET/CT accuracy in patients "on
      therapy" with suppressed thyroid stimulating hormone (TSH) and those with high
      TSH levels. METHODS: We studied 52 patients who had undergone total thyroidectomy
      and remnant ablation; they had high Tg levels (average = 156 ng/mL; SD +/- 274)
      after 3 weeks of levothyroxine withdrawal and negative I-131 total body scans
      after therapeutic doses. RESULTS: We noted a statistically significant positive
      correlation between F-18 FDG-PET/CT positive results and Tg levels, irrespective
      of levothyroxine therapy regimen. Tg levels between F-18 FDG-PET/CT
      positive/negative groups were significantly different and we did not note any
      statistically significant correlation between F-18 FDG-PET/CT results and TSH
      levels, tumor size, and combination of Tg/TSH levels. CONCLUSIONS: Our results
      indicate that F-18 FDG-PET/CT is a useful diagnostic tool in patients with
      differentiated thyroid carcinoma and with negative I-131 total body scans and
      high Tg levels. The levothyroxine therapy regimen does not influence F-18 FDG
      PET/CT results and the rate of F-18 FDG-PET/CT positive results appears to
      correlate with the Tg levels. The highest accuracy is reached when the study is
      performed for patients with Tg levels higher than 21 ng/mL.

PMID- 19851170
TI  - Doxorubicin-induced cardiac toxicity and cardiac rest gated blood pool imaging.
AB  - Anthracyclines are one of the most commonly used and potent chemotherapeutic
      agents. Doxorubicin (Adriamycin) is one common anthracycline used to treat many
      solid tumors including breast, sarcomas, gynecologic and hematological
      malignancies, such as leukemias and lymphomas. However, its use is often limited
      due to dose-dependent cardiotoxicity. As a result, patients receiving doxorubicin
      should have close monitoring of their left ventricular function. The gated
      cardiac blood pool (GBP) study is one of the most accurate and reproducible
      methods of assessing left ventricular function. This report presents an overview
      of (1) the incidence, clinical course, mechanisms, pathology, prevention, and
      monitoring of doxorubicin-induced cardiotoxicity (DIC), (2) the use of GBP
      studies in monitoring for DIC, and (3) 2 algorithms for the use of GBP studies in
      monitoring for DIC. This report concludes with a proposed algorithm for the use
      of GBP studies in DIC. With an understanding of DIC, GBP studies, and various
      algorithms, the interpreting physician may help the oncologist identify DIC
      earlier, more accurately, and before it becomes clinically apparent.

PMID- 19851172
TI  - Patterns of three-phase bone scintigraphy according to the time course of complex
      regional pain syndrome type I after a stroke or traumatic brain injury.
AB  - We have proposed to evaluate different patterns represented on 3-phase bone
      scintigraphy (TPBS) according to the time course of complex regional pain
      syndrome (CRPS) type I (CRPS-I) after a stroke or traumatic brain injury. TPBS
      was performed in 50 consecutive patients for the evaluation of CRPS. We divided
      the patients into CRPS and non-CPRS groups based on the use of International
      Association for the Study of Pain criteria. We evaluated the changes on TPBS
      according to clinical stages based on time course. In the early acute stage
      within 6 weeks, minimal uptake on all TPBS phases was observed in the 90% of the
      patients in the CRPS-I group and in 75% of the patients in the non-CRPS group. In
      the acute stage of CRPS in the range of 2 to 20 weeks, moderately increased
      uptake was seen for 78%, 83%, and 83% of the patients in the CRPS group for the 3
      phases, respectively. However, only 16% of the patients in the non-CRPS group had
      moderately increased uptake as seen on all TPBS phases. In the late stage of more
      than 21 weeks, there was no distinct difference in uptake between the 2 groups. A
      sequential change during the time course for the CPRS-I group was statistically
      significant (P < 0.05). Therefore, performance of follow-up TPBS may be useful to
      diagnose CPRS-I in uncertain cases of the early acute stage after a stroke or
      traumatic brain injury.

PMID- 19851171
TI  - Temporal hypoperfusion assessed by cerebral blood flow SPECT and long-term
      clinical outcome in patients with eating disorders.
AB  - OBJECTIVE: To evaluate the relationship between temporal hypoperfusion in the
      acute phase of patients with eating disorders and the long-term clinical outcome.
      METHOD: Brain perfusion was studied using Tc-99m HMPAO SPECT in 17 patients with
      eating disorders (ED) and compared with 12 controls (C). Semiquantitative
      analysis was carried out by left/right indexes. Clinical records were reviewed 15
      years later and the patients were classified into 2 groups: bad outcome in 10
      patients and good outcome in 4. The results of the basal SPECT were compared with
      the clinical outcome. RESULTS: The mean of the differences of temporal perfusion
      in the lower slice was 0.1476 +/- 0.1121 in ED and 0.03 +/- 0.019 in C (P <
      0.001). Comparisons between C and bad outcome showed a significant difference (P
      < 0.01). There was no significant difference between good outcome and C.
      CONCLUSIONS: The temporal hypoperfusion in the acute phase of patients with ED
      showed a correlation with the long-term clinical outcome and suggested a
      prognostic value of temporal hypoperfusion.

PMID- 19851173
TI  - Late FDG PET normalization after radioimmunotherapy in a patient with non-Hodgkin
      lymphoma.
AB  - Fluoro-deoxy-glucose positron emission tomography (FDG PET) has largely been used
      for response assessment after treatment of lymphoma, resulting in a very
      sensitive and specific imaging technique for the detection of residual disease.
      For this reason FDG PET has recently been proposed to be integrated in the
      International Workshop Criteria. In this report, a patient with non-Hodgkin
      lymphoma was treated with radioimmunotherapy for disease relapse, demonstrated by
      PET. Post-treatment evaluation was performed 9 weeks after treatment, and PET
      showed almost complete disappearance of tracer uptake, but with faint persistence
      of uptake at 1 iliac node and thus was a suspect for residual disease. However, a
      wait-and-see approach was decided and the patient was rescanned with PET 18 weeks
      after treatment, and the results were finally negative. This case indicates that
      after completion of radioimmunotherapy it may be recommended to wait several
      weeks before performing a PET scan and, in case of minimal findings, to consider
      a short-term re-evaluation.

PMID- 19851174
TI  - Hybrid SPECT/CT imaging for primary hyperparathyroidism: case reports and
      pictorial review.
AB  - The utility of hybrid single photon emission computed tomography/computed
      tomography imaging for primary hyperparathyroidism is both intuitive and becoming
      increasingly apparent clinically, particularly for patients with prior failed
      surgery and for those with suspected ectopic adenomas. Second generation imaging
      equipment, capable of superimposing functional information on highly detailed
      anatomic images is proving useful in surgical planning, permitting the successful
      application of minimally invasive techniques. The clinical background and hybrid
      imaging modality are discussed, together with a selection of illustrative case
      images. Special emphasis is placed on the use of the technique for imaging
      ectopic parathyroid adenomas.

PMID- 19851175
TI  - F-18 PET-CT showing large vessel vasculitis in a patient with high inflammatory
      markers and no localizing symptoms.

PMID- 19851176
TI  - F-18 FDG PET/CT findings in a case of gastric relapse of acute myeloblastic
      leukemia.

PMID- 19851177
TI  - Biliary non-Hodgkin lymphoma detected by F-18 FDG PET/CT.

PMID- 19851178
TI  - Histological transformation of follicular lymphoma after treatment: a case
      evaluated with PET/CT.

PMID- 19851179
TI  - McCune-Albright Syndrome: intensely hypermetabolic polyostotic fibrous dysplasia
      on F-18 FDG-PET.

PMID- 19851180
TI  - F-18 FDG PET evaluation of a rapidly growing extraocular sebaceous carcinoma.

PMID- 19851181
TI  - F-18 FDG PET/CT imaging of cortical bone metastases.

PMID- 19851182
TI  - Bone scintigraphic images of a patient with unusual metastatic alveolar soft-part
      sarcoma.

PMID- 19851183
TI  - Postsurgical atypical F-18 fluorodeoxyglucose positron emission tomography
      uptake.

PMID- 19851184
TI  - Fulminant postirradiation soft tissue sarcoma.

PMID- 19851185
TI  - Abnormal FDG PET imaging in tuberculosis appearing like mesothelioma: anatomic
      delineation by CT can aid in differential diagnosis.

PMID- 19851186
TI  - PET scanning used for monitoring treatment response in Mycobacterium avium
      complex infection mimicking malignancy.

PMID- 19851187
TI  - F-18 FDG PET/CT findings showing lymph node uptake in patients with Kikuchi
      disease.

PMID- 19851188
TI  - High F-18 FDG uptake in bone marrow by cytokines secreting ectopic mucoepidermoid
      carcinoma.
AB  - A 57-year-old woman, just returned from a bicycling holiday in the mountains,
      presented with discomfort, hoarseness and chronic cough complaints. After chest x
      ray, bronchoscopy and fluoro-deoxy-glucose positron emission tomography/computed
      tomography (F-18 FDG PET/CT), a diagnosis of a tumor in the bronchus of the right
      upper lobe with obstruction pneumonia was made. After lobectomy of the right
      upper lobe, pathology revealed an ectopic bronchial low-grade mucoepidermoid
      carcinoma.The diffuse high FDG uptake in the bone marrow standardized uptake
      value (SUV mean 3.6 and max 5.2) is unlikely to be related to bone marrow
      stimulation due to pneumonia, but correlates with a high serum level of
      correlated with transforming growth factor-beta (TGF-beta1) secreted by the low
      grade bronchial mucoepidermoid carcinoma.

PMID- 19851189
TI  - PET/CT appearance of intestinal Behcet disease.

PMID- 19851190
TI  - Gallbladder cancer presenting as an isolated large lung mass.

PMID- 19851191
TI  - Delayed diuretic FDG PET/CT scan facilitates detection of renal urothelial cell
      carcinoma.

PMID- 19851192
TI  - Cerebellopontine angle schwannoma on C-11 acetate PET/CT.

PMID- 19851193
TI  - Tc-99m MDP bone scintigraphy in septic shock.

PMID- 19851194
TI  - Coexistant iodine-negative pleural metastasis with iodine-positive lung and bone
      metastases in a patient with differentiated thyroid cancer.

PMID- 19851195
TI  - Current readings in nuclear medicine.

PMID- 19851196
TI  - History of gynecological pathology XXIII. Jean-Paul Andre Latour, MD, CM.

PMID- 19851197
TI  - Comparative analysis of P16 and P53 expression in uterine malignant mixed
      mullerian tumors.
AB  - Recent studies have shown that, in addition to cervical carcinomas, a substantial
      proportion of endometrial adenocarcinomas are also immunoreactive with p16. The
      expression of p16 in uterine malignant mixed mullerian tumors (MMMTs), in
      contrast, has not yet been analyzed in a large series. To our knowledge, we
      present the first study assessing p16 expression in both components of MMMTs. We
      performed p16 and p53 immunostains on 30 cases of uterine MMMTs. Both the
      epithelial and mesenchymal components were subclassified; p16 and p53
      immunoreactions were assessed using a semiquantitative scoring system. p16
      overexpression was noted in the carcinomatous component in 96.7% (29/30), and in
      the sarcomatous component in 86.7% (26/30) of cases. In comparison, p53
      immunoreactivity was present in the carcinomatous component in 76.7% (23/30), and
      in the sarcomatous component in 83.3% (25/30) of cases. p16 immunoreactivity was
      more intense and diffuse than p53 in 40% of type I, 30% of type II carcinomas,
      and 27% of sarcomatous components. There was no significant difference in p16 or
      p53 immunoreactivity between the homologous and heterologous sarcomas. The
      concordance rates for p16 and p53 immunoreactivity between the 2 components were
      83% and 90%, respectively. We conclude that p16 immunostain is positive in the
      vast majority of uterine MMMTs with no significant difference in staining between
      the 2 components. Compared with p53, p16 immunoreactivity is significantly more
      intense and diffuse in both components. Our findings indicate that alterations in
      the p16-Rb pathway play an important role in the pathogenesis of uterine MMMTs.

PMID- 19851198
TI  - Endometrial polyps and the risk of atypical hyperplasia on biopsies of
      unremarkable endometrium: a study on 694 patients with benign endometrial polyps.
AB  - The objective of our study was to examine the relationship between benign
      endometrial polyps and the underlying endometrium, analyzing factors associated
      with endometrial hyperplasia with and without atypia. Six hundred and ninety-four
      consecutive patients with benign endometrial polyps underwent hysteroscopic
      removal of the polyps combined with 2 biopsies of unremarkable endometrium.
      Hysteroscopic removal of endometrial polyps with 2 endometrial biopsies far from
      the base of the polyp were performed. The weight of each polyp was determined.
      Multivariable logistic regression analysis was used examining factors potentially
      associated with endometrial hyperplasia with and without atypia on endometrial
      biopsies. Overall, 18% of women had hyperplasia without atypia and 7.3% had
      atypia (with simple/complex hyperplasia) on hysteroscopically unremarkable
      endometrium. In postmenopause, 21.6% had hyperplasia without atypia, 12% atypia,
      and 1.2% adenocarcinoma on the sampled endometrium. At multivariable analysis,
      postmenopausal women with larger polyps had a 3.6-fold higher likelihood of
      atypia (odds ratio=3.6; 95% confidence interval: 1.3-10.3); in premenopause the
      likelihood of atypia was significantly associated with polyp weight and age above
      40 years. Our findings suggest that important endometrial lesions are not always
      evident by hysteroscopic visualization. Therefore, endometrial biopsies should
      not be limited only to hysteroscopically evident lesions. Polypectomy should be
      combined with a histopathologic evaluation of the background endometrium,
      particularly in women with higher-risk characteristics.

PMID- 19851199
TI  - Atypical leiomyomas of the uterus with long-term follow-up after myomectomy with
      immunohistochemical analysis for p16INK4A, p53, Ki-67, estrogen receptors, and
      progesterone receptors.
AB  - Atypical leiomyomas are characterized by moderately to severely pleomorphic
      atypical tumor cells with low mitotic counts and no coagulative tumor cell
      necrosis. Despite the worrisome histologic features, most tumors have shown
      benign behavior. However, most studied patients had total hysterectomies, and
      very few patients who had myomectomy alone have had long-term follow-up. The
      behavior of atypical leiomyomas treated with myomectomy alone is still not known.
      We present a study of 13 atypical leiomyomas treated with myomectomy alone with
      long-term follow-up results and immunohistochemical findings for p16 (p16), p53,
      Ki-67, estrogen receptors, and progesterone receptors. The lengths of the
      postoperative intervals ranged from 20 to 151 months (mean=76.1 mo). None of the
      patients had developed a metastasis of her atypical leiomyoma. However, 1 patient
      showed local recurrence at the past myomectomy site 22 months after initial
      myomectomy. Immunostaining for p16 showed moderate to strong diffuse
      immunoreactivity in 11/13 cases (84.6%) of atypical leiomyomas, and 38.5% showed
      immunoreactivity for p53, including 1 case with strong, diffuse positive p53.
      When an atypical leiomyoma is discovered in a myomectomy specimen, the patient
      should be carefully followed up with or hysterectomy could be recommended. Larger
      numbers of cases and more long-term follow-up studies are needed to confirm the
      safety of myomectomy for atypical leiomyomas.

PMID- 19851200
TI  - Synchronous presentation of uterine leiomyosarcoma and retroperitoneal
      liposarcoma: analysis by comparative genomic hybridization and review of the
      literature.
AB  - Multiple primary malignant neoplasms are not uncommon, whereas 2 different types
      of primary sarcomas simultaneously presenting in 1 individual is quite unusual.
      We encountered a patient presenting with a uterine sarcoma and another
      retroperitoneal mass at the same time. These 2 tumors showed distinct pathologic
      and immunohistochemical features. The diagnosis of a synchronous presentation of
      a uterine leiomyosarcoma and a retroperitoneal sclerosing well-differentiated
      liposarcoma was rendered. Further study by comparative genomic hybridization
      showed unrelated genomic alterations of these 2 tumors. Nevertheless, other
      common genetic alterations such as balanced translocations, point mutations, or
      epigenetic modifications could still exist because of the limitation of findings
      by comparative genomic hybridization. In conclusion, both metastasis and multiple
      primary tumors should always be taken into consideration in differential
      diagnosis while encountering synchronous sarcomas.

PMID- 19851201
TI  - Human papillomavirus types in invasive cervical cancer specimens from Turkey.
AB  - The main aim of the study is to describe the human papillomavirus (HPV) type
      specific distribution in invasive cervical cancer (ICC) specimens from Turkey.
      Paraffin-embedded ICC specimens were identified from the histopathologic archives
      of the Hacettepe University Medical School in Turkey. HPV detection was carried
      out through amplification of HPV DNA by a SPF-10 broad-spectrum primer polymerase
      chain reaction and subsequently followed by DNA enzyme immunoassay and genotyping
      by LiPA25 (version 1). Two hundred seventy-seven ICC cases diagnosed between 1993
      and 2004 were retrieved. After histologic evaluation and human beta-globin gene
      analysis for sample quality, 248 cases were considered suitable for HPV/DNA
      testing. HPV prevalence was 93.5% (232/248; 95% confidence interval: 90.5%
      96.6%). The five most common HPV types identified as single types among HPV
      positive cases were HPV16 (64.7%), HPV18 (9.9%), HPV45 (9.9%), HPV31 (3.0%), and
      HPV33 (2.2%). The study shows that in Turkey, HPV16/HPV18 accounted for 75.4%
      (95% confidence interval: 69.9%-81.0%) of HPV-positive ICC cases. This
      information is essential to evaluate the potential impact of the HPV vaccines in
      the country.

PMID- 19851202
TI  - The effect of cigarette smoking on cervical langerhans cells and T and B
      lymphocytes in normal uterine cervix epithelium.
AB  - The objective of our study was to evaluate the effect of smoking on
      intraepithelial Langerhans cells and T and B lymphocytes in normal cervical
      epithelium. A total of 47 women who underwent hysterectomies because of uterine
      leiomyomata were investigated. Thirty-two individuals were nonsmokers and 15 were
      current smokers. A segment of tissue was taken from the cervix after the removal
      of the uterus and was formalin-fixed and paraffin-embedded for histologic
      analysis. The identification of the Langerhans cells and T and B lymphocytes was
      carried out by immunohistochemical analysis. The number of intraepithelial
      Langerhans cells was expressed by the amount of cells per square millimeter of
      epithelium. For T and B lymphocytes, a score expressed the cell count. The
      comparison of the number of intraepithelial Langerhans cells between smoking and
      nonsmoking women showed a significant difference (P=0.045), but it did not occur
      in relation to the number of T and B cells between the 2 groups. There was also
      no significant difference in relation to the number of cigarettes smoked per day,
      time of consumption, and total amount of cigarettes smoked throughout the
      lifetime. It was shown that smoking reduces the number of intraepithelial
      Langerhans cells in a normal cervix but does not influence the number of T and B
      lymphocytes.

PMID- 19851203
TI  - Diagnosis of vulval inflammatory dermatoses: a pathological study with clinical
      correlation.
AB  - Diagnosis of vulval inflammatory disease is difficult. In this study, we reviewed
      31 vulval biopsies from 23 patients with clinical follow-up. We devised 2 scoring
      systems from recent publications to determine whether these could help to
      distinguish between lichen sclerosus (LS) and lichen planus (LP). We found that
      scoring systems could help in distinguishing LS from LP but that they were no
      better than using some select pathologic criteria, and were much more time
      consuming. Most cases of LS had characteristic dermal sclerosis. LP cases had a
      characteristic band-like inflammatory infiltrate and did not always have features
      such as pointed rete ridges, wedge-shaped hypergranulosis and cytoid bodies as
      observed in nonvulval sites. Eczema was the third most common dermatosis in the
      study and had features that could also be observed in LS, such as acanthosis,
      abnormal collagen, and ectatic blood vessels. However, dermal sclerosus was not
      observed. Loss of dermal elastin fibers was observed in both LS and LP and thus
      did not help in discriminating between the 2 conditions. Oral LP elsewhere in the
      body was common and was observed in 20% of both the LS and LP group. A small
      proportion of patients did not fit into any category. We believed that it was
      important not to label patients as having a disease unless specific features were
      observed. It may be in their best interests to be called nonspecific rather than
      being put in the wrong disease category.

PMID- 19851204
TI  - Accuracy of preoperative vulva biopsy and the outcome of surgery in vulvar
      intraepithelial neoplasia 2 and 3.
AB  - To assess the accuracy of preoperative vulva biopsy and the outcome of surgery in
      vulvar intraepithelial neoplasia (VIN) 2 and 3. In this study 186 consecutive
      patients with VIN 2 and 3, who were treated with local wide excision or skinning
      vulvectomy at the Department of Obstetrics and Gynecology, Medical University of
      Vienna, between 1996 and 2008, were enrolled. Accuracy of preoperative vulva
      biopsy was assessed by evaluating the rates of correct diagnosis, underdiagnosis,
      and occult cancer. Histologic findings of preoperative vulva biopsy and surgery
      were compared. To assess risk factors for incomplete resection, univariate and
      multivariate analyses were performed, by using the presence of multifocal VIN,
      histologic grade, patients' age, surgeons' expertise, and lesion diameter as
      independent variables. VIN 2 and 3 were correctly diagnosed by preoperative vulva
      biopsy in 55.8% (29/52) and 88.1% (118/134) patients, respectively.
      Underdiagnosis occurred in 44.2% (23/52) and 11.9% (16/134) of preoperative vulva
      biopsies with an occult cancer rate of 3.8% (2/52) and 11.9% (16/134) for VIN 2
      and 3, respectively. Complete resection was achieved in 43.0% (80/186) of
      patients. Presence of multifocal VIN was the only factor that was associated with
      incomplete resection in our study population in univariate and multivariate
      analyses (P=0.001, P=0.001). Mean patients' age at the time of diagnosis was 51.1
      (SD: 15.7) years, multifocal lesions were present in 36.0% (67/186), and the
      median lesion diameter was 15.0 mm (interquartile range: 10.0-30.0). A
      significant number of VIN 2 and 3 were underdiagnosed by preoperative vulva
      biopsy. The rate of incomplete resection after surgery is notable.

PMID- 19851205
TI  - Tubulo-squamous vaginal polyp with basaloid epithelial differentiation.
AB  - Tubulo-squamous polyp is a recently described and apparently benign lesion that
      most frequently involves the upper vagina of postmenopausal patients.
      Histologically, it is characterized by the presence of cysts, squamous epithelial
      nests, and small tubular structures that are surrounded by a hypocellular fibrous
      stroma. Some lesions show focal immunoreactivity for prostatic acid phosphatise
      and/or prostate-specific antigen raising the possibility of derivation from
      Skene's glands. In this report, an additional case of tubulo-squamous polyp is
      presented in which there was prominent basaloid epithelial differentiation,
      mainly in the form of elongated cords of cells around the peripheral and deep
      aspect of the lesion. This feature has not been recorded previously in tubulo
      squamous polyp and potentially could create diagnostic difficulty with other
      lesions such as basal cell/adenoid basal carcinoma or small-cell neuroendocrine
      carcinoma.

PMID- 19851207
TI  - Squamous intraepithelial lesions arising in benign endocervical polyps: a report
      of 9 cases with correlation to the pap smears, HPV analysis, and immunoprofile.

PMID- 19851208
TI  - Mantle structures in the uterine cervix.

PMID- 19851209
TI  - PAX 2: a novel Mullerian marker for serous papillary carcinomas to differentiate
      from micropapillary breast carcinoma.
AB  - Ovarian serous papillary carcinoma, although rarely metastasizing to the breast,
      is often challenging based on morphology alone, particularly from the
      micropapillary variant of breast carcinoma. Gross cystic disease fluid protein
      15, although a specific marker, can be negative in up to 50% of breast
      carcinomas. Wilm's tumor gene 1 (WT-1) has been identified as a useful marker to
      differentiate metastatic ovarian serous papillary carcinoma from primary breast
      carcinoma; however, it has recently been shown in the micropapillary variant of
      the primary breast carcinoma making it a less specific marker. PAX 2, a nuclear
      transcription factor, was recently observed in ovarian serous papillary
      carcinomas. In this study of 89 breast carcinoma cases, 26 micropapillary
      carcinoma, and 63 nonmicropapillary carcinoma types were retrieved from our
      pathology archives, represented on a single tissue microarray (TMA) with a 3-fold
      redundancy (TMA-1, TMA-2). In addition, whole tissue sections of a variety of
      benign and neoplastic mullerian tissues were surveyed with the PAX 2 immunostain.
      All cases were stained with rabbit polyclonal PAX 2 antibody and, in addition,
      the 5 metastatic ovarian serous carcinoma cases were stained with WT-1 as well
      for comparison. Only nuclear staining was considered positive. All primary breast
      carcinomas represented on TMA-1 and TMA-2 were entirely negative for PAX 2 100%
      (89/89), whereas 100% (5/5) of all metastatic ovarian serous carcinomas showed
      moderate-to-strong staining. PAX 2 expression was comparable with WT-1 as well in
      the metastatic ovarian serous carcinoma group. We therefore conclude that PAX 2
      is a promising new, sensitive, and specific mullerian immunomarker for ovarian
      serous carcinomas (primary and metastatic).

PMID- 19851210
TI  - Ovarian involvement by desmoplastic small round cell tumor with leydig cell
      hyperplasia showing an unusual immunophenotype (cytokeratin negative, calretinin
      and inhibin positive) mimicking poorly differentiated sertoli leydig cell tumor.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare aggressive tumor primarily
      involving serosal surfaces in adolescents and young men. Diagnosis is based on
      specific clinicomorphologic, immunohistochemical, and genetic features. We report
      here a variant of DSRCT involving the ovaries that mimics the Sertoli-Leydig cell
      tumor in a 21-year-old woman complaining of abdominal pain. Abdominal
      ultrasonography and computed tomography showed a right adnexal mass. She had a
      slightly raised serum CA-125 level. Frozen section examination identified the
      right ovarian mass as a poorly differentiated Sertoli-Leydig cell tumor. The
      surgically resected tumor and left ovary and omentum implants found during
      laparoscopy were diagnosed as DSRCT with Leydig cell hyperplasia.
      Immunohistochemically, the tumor cells were negative for epithelial markers but
      were positive for calretinin and inhibin. The patient is still undergoing
      chemotherapy at 8 months after initial presentation with partial response. This
      case showed that DSRCT with unusual immunohistochemical profiles and Leydig cells
      hyperplasia pose a diagnostic challenge. Molecular genetic techniques may help in
      these cases.

PMID- 19851211
TI  - Ovarian clear cell carcinoma arising in a mucinous cystadenoma.
AB  - Here we report a rare case of ovarian clear cell carcinoma (CC) arising in a
      mucinous cystadenoma. A 59-year-old woman presented with a dull pain at the left
      inguinal area. She was found to have a left ovarian cyst measuring 4.7 cm and
      underwent a salpingo-oophorectomy. The unilocular cyst contained thick mucin,
      lacking any solid components. Histopathologically, most of the cyst wall was
      lined with a single layer of tall columnar cells with basophilic mucin. Within
      limited areas, small glands consisting of clear cytoplasm aggregated and
      intermingled with or partially transitioned to the mucinous glands. The clear
      cell components had adenofibroma-like features devoid of significant nuclear
      atypia or stromal invasion, including distinctive foci of CC with a hobnail
      appearance and hyperchromatic nuclei surrounded by desmoplastic or hyalinized
      stroma. Immunohistochemically, both mucinous and clear cells were positive for
      estrogen receptor. Hepatocyte nuclear factor-1beta and laminin were positive in
      all of the clear cell components, in contrast to a consistent lack of staining in
      the mucinous epithelium. An eleven-month follow-up revealed no recurrence or
      metastasis. This case was considered as an early manifestation of ovarian CC
      arising in a mucinous cystadenoma in the absence of demonstrable endometriosis.

PMID- 19851212
TI  - Malignant variant of sclerosing perivascular epithelioid cell tumor arising in
      the adnexa.
AB  - The perivascular epithelioid cell family of tumors (PEComas) includes
      angiomyolipoma, lymphangioleiomyomatosis, clear-cell "sugar" tumor of the lung
      and a variety of extrapulmonary epithelioid and spindle-cell tumors referred to
      by various names. PEComas are now widely recognized histologically, and have been
      reported to occur at most anatomical sites, including the female genital tract.
      However, a distinctive variant of PEComa, designated "sclerosing PEComa," has
      only recently been described in the literature. All 13 of the cases of sclerosing
      PEComa reported thus far have been in women (mean age of 49 y), with a
      predilection for the retroperitoneum. Only one of the reported cases showed
      transition to a high-grade malignant phenotype. We report the first case of
      sclerosing PEComa arising in the uterine adnexa, with high-grade malignant
      transformation.

PMID- 19851213
TI  - Lymph node involvement in multicystic peritoneal mesothelioma.
AB  - Multicystic peritoneal mesothelioma is an uncommon lesion most frequently
      encountered in women of reproductive age. Although the pathologic characteristics
      have been documented, the lymph node status associated with this pathology, the
      etiopathogenesis and prognosis of which remain unclear, is unknown. We report
      here the case of a 35-year-old woman with a 5.5 cm multicystic mesothelioma
      affecting the pelvic peritoneum of the rectum. Involvement by multicystic
      mesothelioma was observed within two lymph nodes simultaneously resected with the
      tumor. To the best of our knowledge, lymph node involvement has not been
      described in previous studies.

PMID- 19851215
TI  - High-risk non-ST-segment elevation myocardial infarction versus ST-segment
      elevation myocardial infarction: same behaviour and outcome?
AB  - Despite advances in the treatment of acute coronary syndromes (ACS) a large
      proportion of patients do not receive adequate treatment. In most cases,
      myocardial infarction with ST-segment elevation myocardial infarction (STEMI) is
      associated with thrombotic occlusion of a major coronary artery, and 30-day
      mortality is higher than for patients with non-ST-segment elevation myocardial
      infarction (NSTEMI). In patients with NSTEMI, however, the mortality rate
      increases after discharge, becoming close to that seen in STEMI patients at 6
      months. Whereas patients with STEMI usually undergo emergent revascularization,
      the clinical scenario in NSTEMI is extremely variable and, in most cases, high
      risk patients do not undergo coronary angiography at the times recommended in the
      European Society of Cardiology guidelines. Unlike NSTEMI, STEMI is associated
      with a very high risk of mortality in 30% of cases, whereas the remaining 70% of
      cases have a short-term mortality risk of less than 5%. The application of
      accurate models for risk prediction may significantly improve survival in these
      patients, thus avoiding emergent revascularization in low to medium-risk
      patients. This approach may lead to a redistribution of care across the spectrum
      of ACS, thus giving priority when the risk/benefit ratio is higher, independent
      of electrocardiogram results at presentation.

PMID- 19851216
TI  - Stent choice in primary percutaneous coronary intervention: drug-eluting stents
      or bare metal stents?
AB  - The controversial choice between bare metal stents and drug-eluting stents (DES)
      in primary percutaneous coronary intervention (PCI) seems to be driven by a
      growing body of evidence. Although evidence supporting the use of DES in the
      setting of ST-segment elevation myocardial infarction (STEMI) has been
      demonstrated, including a lower target vessel revascularization (TVR) rate
      without increased mortality, at present the proportion of DES implants in STEMI
      patients is low. This may be due to higher costs of DES, cultural issues, lack of
      concerns about restenosis in STEMI, lack of information on patient bleeding risk
      and the need for surgery within a limited time. In addition, initial enthusiasm
      about the efficacy of DES in reducing restenosis is now decreasing as a result of
      the safety concerns regarding in-stent thrombosis. Moreover, DES requires long
      term dual antiplatelet therapy (DAT), which may pose problems in patients prone
      to bleeding or in candidates for elective surgery. Nevertheless, benefits
      associated with use of DES include significantly lower TVR rates without
      remarkable adverse effects in terms of death and myocardial infarction. Data
      about the efficacy of DES are still limited to 1-year follow-up in most trials.
      Uncoated stents permit early arterial wall healing, requiring a shorter duration
      of DAT and are potentially associated with a reduced risk of thrombus formation
      at long-term follow-up. Importantly, however, this potential late threat has not
      been confirmed in recent data from the limited number of studies with longer than
      2-years follow-up. Anatomical features and individual risk profiles can sometimes
      help in the choice of the most suitable type of stent. In conclusion, stent
      choice in primary PCI cannot be standardized for all patients and appears to be
      influenced by various factors that need to be considered to provide better
      revascularization in terms of both efficacy and safety.

PMID- 19851217
TI  - Primary percutaneous coronary intervention: different outcome for different
      subgroups?
AB  - Over the past 20 years, the widespread use of pharmacological and mechanical
      reperfusion therapies, as well as a faster delivery of care, has considerably
      improved survival in acute coronary syndromes. Primary percutaneous coronary
      intervention (PCI), in particular, has improved the long-term prognosis of
      patients with ST-segment elevation myocardial infarction. There are, however,
      particular subgroups of individuals (elderly patients, women and patients with
      chronic kidney disease) that require special management during PCI because of
      their higher risk profile and the presence of numerous other concomitant
      pathologies. To date, a general consensus on the management of these patients in
      different phases of their clinical course is still lacking, but it is largely
      acknowledged that patients with the highest risk profile are often denied a
      reperfusion treatment.

PMID- 19851218
TI  - ST-segment elevation myocardial infarction management in Europe.
AB  - The rate of percutaneous coronary intervention (PCI) for ST-segment elevation
      myocardial infarction varies between European countries, as does total mortality
      as a result of acute myocardial infarction. These differences arise partly
      because of differences between countries in the time delay from symptom onset to
      first medical contact, and from first medical contact to reperfusion with
      thrombolysis or PCI. The European Society of Cardiology guidelines emphasize the
      importance of early reperfusion therapy. There are, however, often logistical
      delays in transport of the patient, in diagnosis of myocardial infarction and in
      preparation of medical teams to be available to perform PCI. Studies have shown
      that door-to-balloon time may improve with an integrated approach coordinating
      systems, procedures and institutions, and steps such as including prehospital
      triage and prehospital electrocardiogram transmission can dramatically reduce
      door-to-balloon time. Early transfer to PCI is associated with fewer ischaemic
      complications.

PMID- 19851219
TI  - How to reduce the time windows for primary percutaneous coronary intervention.
AB  - Percutaneous coronary intervention (PCI) is an effective procedure for re
      establishing coronary artery perfusion in ST-segment elevation myocardial
      infarction. PCI is the preferred therapeutic option when it can be performed by
      an experienced team within 90-120 min of the first medical contact. Time from the
      onset of symptoms to balloon inflation seems to correlate directly with mortality
      rates. We discuss both hospital strategies and territorial system networks aimed
      at reducing the time windows for primary PCI, thereby improving clinical outcome
      and survival rates.

PMID- 19851220
TI  - Understanding axis deviation.

PMID- 19851221
TI  - Taking obstructive sleep apnea to heart.

PMID- 19851222
TI  - Long QT syndrome: dangerous delay.

PMID- 19851223
TI  - The role of coronary computed tomography angiography.

PMID- 19851225
TI  - Brain development of the preterm neonate after neonatal hydrocortisone treatment
      for chronic lung disease.
AB  - Previous studies reported impaired cerebral cortical gray matter (CGM)
      development and neurodevelopmental impairment after neonatal dexamethasone
      treatment for chronic lung disease (CLD) in preterm newborns. No long-term
      effects on neurocognitive outcome have yet been shown for hydrocortisone
      treatment. A prospective study was performed to evaluate the brain growth at term
      in preterm infants who did receive neonatal hydrocortisone for CLD. Thirty-eight
      preterm infants (n = 19 hydrocortisone, n = 19 controls) were matched for
      gestational age at birth. Gestational age and birth weight were 27.0+/- 1.4
      versus 27.6+/- 1.1 wk (p = ns) and 826+/- 173 versus 1017+/- 202 g, respectively
      (p < 0.05). Infants were studied at term equivalent age. Hydrocortisone was
      started with a dose of 5 mg/kg/d for 1 wk, followed by a tapering course over 3
      wk. A 3D-MRI technique was used to quantify cerebral tissue volumes: CGM, basal
      ganglia/thalami, unmyelinated white matter, myelinated white matter, cerebellum,
      and cerebrospinal fluid. Infants who were treated with hydrocortisone had more
      severe respiratory distress. There were no differences in cerebral tissue volumes
      between the two groups at term equivalent age. In conclusion, no effect on brain
      growth, measured at term equivalent age, was shown after treatment with
      hydrocortisone for CLD.

PMID- 19851226
TI  - Persistence of essential fatty acid deficiency in cystic fibrosis despite
      nutritional therapy.
AB  - To study the evolution of plasma fatty acid composition of patients with cystic
      fibrosis (CF) in relation to nutritional status, pancreatic function, and
      development of CF-related liver disease (CFRLD) and diabetes mellitus, 24 CF
      pediatric patients with stable pulmonary disease were studied before and after an
      approximate period of 8 y. Nutritional status, pulmonary function, pancreatic
      function, and presence of CFRLD or diabetes mellitus were recorded. Results were
      compared with data obtained in 83 healthy children. Patients with CF have
      significantly lower linoleic acid (LA), docosahexaenoic acid (DHA), lignoceric
      acid, and LA x DHA product and higher oleic acid, mead acid, dihomo-gamma
      linoleic acid, and docosapentaenoic acid (DPA). Comparison of samples taken at
      first and second studies revealed a significant decrease in LA levels and
      lignoceric acid associated with a significant increase in dihomo-gamma-linoleic
      acid levels. Patients with CFRLD showed significantly higher mead
      acid/arachidonic acid ratio and lower total omega6 polyunsaturated fatty acids
      content. There was no relation of plasma fatty acids composition with pancreatic
      function, pulmonary function, or diabetes mellitus. Follow-up of patients with CF
      shows that essential fatty acids deficiency, particularly in LA and DHA content,
      persisted unmodified along time despite an adequate nutritional therapy. Future
      studies after supplementation with omega3 polyunsaturated fatty acids should be
      undertaken.

PMID- 19851230
TI  - Adapting to the context and learning from earlier experience: the implementation
      of a national breakthrough collaborative in the context of social services in
      Sweden.
AB  - BACKGROUND: Although often used in health care settings as a method for
      continuous quality improvement, experience with the breakthrough collaborative in
      nonclinical health care settings is limited. In this article, we report pilot
      data from a social services collaborative conducted in 2007 to 2009 in Sweden,
      with special attention given to features of the implementation context that
      appeared to facilitate or hinder its success. METHODS: We used a case study
      approach to describe the processes used in the pilot project as well as to
      characterize the context. Our analysis was guided by a framework consisting of
      earlier identified factors for success including "motivate and empower the teams"
      and "ensure teams have measurable and achievable targets." RESULTS AND
      CONCLUSION: We observed several context-specific factors. These included
      measuring challenges connected to large cooperating teams. Specifically, teams
      representing different organizations needed more time to carry out a breakthrough
      collaborative than those in clinical health care settings. As in breakthrough
      collaboratives conducted in health care settings, early measurement efforts
      enabled a clearer sense of direction, which may have served to reinforce
      motivation among team members. This study highlights features that may have
      universal importance in influencing the success of breakthrough collaboratives to
      improve the quality of social services.

PMID- 19851231
TI  - Delivering health care on the streets: challenges and opportunities for quality
      management.
AB  - Street Medicine focuses on the health needs of unsheltered homeless through
      mobile teams that provide care in the locations where individuals are found.
      Innovative strategies are needed to manage the quality of care provided within
      the atypical clinical settings encountered. In our study, contextual elements and
      practices for managing quality of care were explored through qualitative analysis
      of program components presented at the 2007 and 2008 International Street
      Medicine Symposia. Our analysis identified several common contextual elements,
      including unconventional living situations and lack of financial resources of
      patients, inconsistency in contact with transient patient populations, and
      informal clinical settings. Several practices were developed to address these
      elements and improve the quality of care delivered. Best practices included the
      use of mobile clinic vans, electronic medical records, collaboration with
      community clinics and hospitals, and provision of comprehensive social support.
      An example of quality auditing was also found in the reviewed programs.
      Additional work is needed to further quality management in Street Medicine and
      support achievement of replicable practices and measurable outcomes. We propose
      that 2 short-term outcome measures be used that acknowledge the contextual
      challenges faced in Street Medicine. These are patient engagement and patients'
      subjective assessment of their well-being.

PMID- 19851232
TI  - Feed forward systems for patient participation and provider support: adoption
      results from the original US context to Sweden and beyond.
AB  - BACKGROUND: This is a study of 2 clinical feed forward systems (FFSs) situated in
      different contexts: in the United States, where the system was developed, and in
      Swedish clinical settings, where it was first adopted. Both systems were
      identified as clinically successful despite differing contexts, and the objective
      of this study is to understand what essential properties determined their
      success. METHODS: In our search for essential properties of the FFS, we used
      acceptance, use, and utility as indicators in questionnaires and interviews of
      patients and providers. Properties were identified as essential if they enabled
      reinforcing loops favorable for patients, providers, or both at clinical
      encounters. RESULTS: A total of 44 patients participated in each context, along
      with 13 providers from the United States and 6 providers from the Swedish
      clinics. In the patient questionnaire, a majority of patients rated their
      impression of the FFS as excellent to good (United States: 84%, Sweden: 96%, P <
      .001). Interviews with both patients and providers indicated that the FFS patient
      overview displaying structured data previous to the clinical encounter is
      favorable. These essential properties enabled patient involvement through
      engagement, education, and communication with the provider, who appreciated them
      as time-saving for managing data and as decision support. DISCUSSION: Despite
      distinctly different contexts and locally adapted content, essential properties
      that induced successful patient participation and provider support were
      identified as universal in the FFSs. Thus, further spread of the FFS may be
      enabled to accomplish patient-centered care and improved clinical information and
      quality management.

PMID- 19851233
TI  - Associations between self-reported quality of care and county characteristics are
      largely similar in rural and urban settings.
AB  - CONTEXT: The content and spectrum of rural health care services are different
      from those in urban areas. The extent to which health care consumers' perceptions
      of the quality of these services vary across settings and the association of
      these perceptions with features of rural and urban settings are unclear.
      OBJECTIVE: To determine whether perceptual differences of quality exist and
      contrast rural/urban associations between contextual characteristics and
      perceived quality of health care. METHODS: Multilevel, cross-sectional analysis
      of a state-representative sample of 33 786 adults, stratified by rural/urban
      status linked with county-level data describing contextual features (eg, health
      care, economics, and social capital). The dependent variable was respondents'
      perceived quality of health care received in the past year. Weighted multilevel
      random intercept models examined the independent association of contextual
      characteristics with perceived quality. RESULTS: Overall perceived quality did
      not differ between rural and urban settings. Similarly, the pattern of
      associations between perceived quality and contextual characteristics was
      generally comparable between settings. A notable difference was an association
      between higher quality with an increasing proportion of hospitals offering more
      than 25 services in urban areas (beta = .763; P < .05). CONCLUSIONS: Despite
      rural/urban differences in contextual characteristics with potential influence on
      health care delivery, overall consumer perception of health care quality was
      similar in both settings. This suggests that health care managers may be adopting
      setting-specific strategies to enhance consumer satisfaction despite contextual
      differences.

PMID- 19851234
TI  - A systematic approach to practice assessment and quality improvement intervention
      tailoring.
AB  - BACKGROUND: The ways in which tailored interventions foster sustained improvement
      in the quality of health care delivery across different practice settings are not
      well understood. Using the empirically developed Practice Change Model (PCM), we
      identify and describe assessment and tailoring activities with potential to
      enhance the fit between proposed interventions and practice settings. METHODS: We
      obtained quantitative and qualitative data from 2 quality improvement trials
      conducted in diverse primary care practices in northeast Ohio. A
      multidisciplinary team used a PCM-based template to identify features of practice
      assessment and tailoring associated with practices' willingness and ability to
      change. RESULTS: Our results suggest that intervention tailoring requires
      assessment of key stakeholders' motivations, external influences, resources and
      opportunities for change, and the interactions between these factors. Using this
      information, intervention tailoring then includes seeking and working with key
      stakeholders, building assets, providing options, keeping change processes
      flexible, offering feedback, providing exposure to scientific evidence,
      facilitating group processes, involving new partners, brainstorming, using
      stories/play acting/humor, assuming a consultant role, reframing, moving meetings
      off-site, and stepping back or pausing. CONCLUSIONS: A model-driven approach
      guiding practice assessment enables tailored responses to the unique and emerging
      conditions that distinguish health care practices and influence implementation of
      quality management interventions.

PMID- 19851236
TI  - Characteristics of health care organizations associated with learning and
      development: lessons from a pilot study.
AB  - Characteristics of health care organizations associated with an ability to learn
      from experiences and to develop and manage change were explored in this study.
      Understanding of these characteristics is necessary to identify factors
      influencing success in learning from the past and achieving future health care
      quality objectives. A literature review of the quality improvement, strategic
      organizational development and change management, organizational learning, and
      microsystems fields identified 20 organizational characteristics, grouped under
      (a) organizational systems, (b) key actors, and (c) change management processes.
      Qualitative methods, using interviews, focus group reports, and archival records,
      were applied to find associations between identified characteristics and 6
      Swedish health care units externally evaluated as delivering high-quality care.
      Strong support for a characteristic was defined as units having more than 4
      sources describing the characteristic as an important success factor. Eighteen
      characteristics had strong support from at least 2 units. The strongest evidence
      was found for the following: (i) key actors have long-term commitment, provide
      support, and make sense of ambiguous situations; (ii) organizational systems
      encourage employee commitment, participation, and involvement; and (iii) change
      management processes are employed systematically. Based on the results, a new
      model of "characteristics associated with learning and development in health care
      organizations" is proposed.

PMID- 19851235
TI  - Measuring practice capacity for change: a tool for guiding quality improvement in
      primary care settings.
AB  - PURPOSE: Capacity for change, or the ability and willingness to undertake change,
      is an organizational characteristic with potential to foster quality management
      in health care. We report on the development and psychometric properties of a
      quantitative measure of capacity for change for use in primary care settings.
      METHODS: Following review of previous conceptual and empirical studies, we
      generated 117 items that assessed organizational structure, climate, and culture.
      Using information from direct observation and key informant interviews, a
      research team member rated these items for 15 primary care practices engaged in a
      quality improvement intervention. Distributional statistics, pairwise correlation
      analysis, Rasch modeling, and item content review guided item reduction and
      instrument finalization. Reliability and convergent validity were assessed.
      RESULTS: Ninety-two items were removed because of limited response distributions
      and redundancy or because of poor Rasch model fit. The final instrument
      comprising 25 items had excellent reliability (alpha = .94). A Rasch model
      derived capacity for change score correlated well with an independently
      determined, qualitatively derived summary assessment of each practice's capacity
      for change (rhoS = 0.82), suggesting good convergent validity. CONCLUSION: We
      describe a new instrument for quantifying organizational capacity for change in
      primary care settings. The ability to quantify capacity for change may enable
      better recognition of practices likely to be successful in their change efforts
      and those first requiring capacity building prior to change interventions.

PMID- 19851237
TI  - Toward more sustainable health care quality improvement in developing countries:
      the "little steps" approach.
AB  - BACKGROUND: Resource constraints are often identified as a hurdle to the
      sustainability of large-scale (national and regional) health care quality
      improvement (QI) programs in developing countries. However, poor fit of a QI
      model with a given country's context may present the greater challenge. METHODS:
      To explore contextual factors influencing the sustainability of large-scale QI
      initiatives in developing countries, we performed a systematic literature review.
      RESULTS: Large-scale initiatives appear to have received significant attention
      only recently in these settings, as priority was traditionally given to extending
      service coverage. Further, these initiatives often relied on QI models
      originating from developed country settings, which differed significantly from
      the systems, resource structures, culture, and values found in the target
      country. The QI programs frequently focused on high-impact/immediate change
      rather than on program sustainability. Barriers to sustainability were identified
      during the planning, start-up, and continuation phases. On the basis of our
      review, greater attention to sustainable methods for large-scale QI in developing
      countries is needed. CONCLUSION: We suggest a "Little Steps" approach that begins
      by defining QI concepts, goals, and processes in a manner congruent with the
      target setting and that builds upon existing systems, structures, and values.
      Despite immediate short-term needs, an approach emphasizing incremental QI
      achievements may be more effective in yielding sustainable improvements in health
      care quality at the national or regional level.

PMID- 19851238
TI  - How work context affects operating room processes: using data mining and computer
      simulation to analyze facility and process design.
AB  - The complexity of the operating room (OR) requires that both structural (eg,
      department layout) and behavioral (eg, staff interactions) patterns of work be
      considered when developing quality improvement strategies. In our study, we
      investigated how these contextual factors influence outpatient OR processes and
      the quality of care delivered. The study setting was a German university
      affiliated hospital performing approximately 6000 outpatient surgeries annually.
      During the 3-year-study period, the hospital significantly changed its outpatient
      OR facility layout from a decentralized (ie, ORs in adjacent areas of the
      building) to a centralized (ie, ORs in immediate vicinity of each other) design.
      To study the impact of the facility change on OR processes, we used a mixed
      methods approach, including process analysis, process modeling, and social
      network analysis of staff interactions. The change in facility layout was seen to
      influence OR processes in ways that could substantially affect patient outcomes.
      For example, we found a potential for more errors during handovers in the new
      centralized design due to greater interdependency between tasks and staff.
      Utilization of the mixed methods approach in our analysis, as compared with that
      of a single assessment method, enabled a deeper understanding of the OR work
      context and its influence on outpatient OR processes.

PMID- 19851239
TI  - The effect of adverse medical events on spending on inpatient care.
AB  - BACKGROUND: In this study, we examined the proposition that the occurrence of
      adverse medical events (AMEs) increases spending on inpatient hospital care.
      METHODS: Employing the individual and the episode of care as the unit of
      analysis, the study relied on data assembled in the Public Use Data File
      maintained by the Oklahoma State Department of Health. Multiple regression
      analyses were used to examine the covariates of the revenue per case and its
      components, the average revenue per day, and the number of days per case.
      RESULTS: The results indicate that the occurrence of AMEs would increase the
      revenue per case, the days of care per case, and the revenue per day.
      CONCLUSIONS: Study findings suggest that a decline in AMEs improves quality while
      lowering spending on hospital care and the use of inpatient services.

PMID- 19851240
TI  - Process improvement in hospitals: a case study in a radiology department.
AB  - To improve processes in hospitals, a case study was conducted at a German
      university hospital, which consists of more than 30 clinics and institutes on a
      large campus. The case study focused on the analysis of the patient flow and of
      machine utilization in the radiology department. Radiological devices are spread
      over the campus and located in different buildings. Patients with restricted
      mobility have to be transported by a vehicle transportation service across the
      campus. However, a vehicle transport can considerably influence the patients'
      punctual arrival to their appointments. The observations of the case study showed
      that the current organization of the radiology department results in high patient
      waiting times and machine idle times. The university hospital is planning to
      conduct significant organizational changes, especially with regard to the
      organization of the radiology department. This case study was conducted to
      support the planning processes of the clinic and to reveal and estimate
      optimization potential. To analyze the patient flow, a discrete event
      multicriteria simulation model was designed and implemented. By modeling
      different scenarios, it was possible to easily compare and assess distinct
      alternatives. This led to improved machine utilization and reduced waiting times.

PMID- 19851243
TI  - Intracorporeal Billroth-I anastomosis using a circular stapler by the abdominal
      wall lifting method in laparoscopy-assisted distal gastrectomy.
AB  - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has recently been
      accepted as a preferred surgical procedure for patient with early gastric cancer.
      The Billroth-I method has been performed widely because of physiologic advantages
      and technical simplicity. METHODS: Since September 2007, we performed
      standardized LADG for 35 patients with early gastric cancer. Of these 35
      patients, 27 patients were reconstructed by Billroth-I anastomosis.
      Gastroduodenostomy was performed under direct vision for 11 patients
      (extracorporeal) and remaining 16 patients were anastomosed under laparoscopic
      vision facilitated by abdominal wall lifting with a right angle retractor
      (intracorporeal). RESULTS: The mean duration of the anastomosis procedure was 17
      and 20 minutes in extracorporeal and intracorporeal patients, respectively. The
      abdominal lifting method with a right angle retractor provided a good visual
      field without reestablishing pneumoperitoneum. The laparoscopic fine view could
      prevent surrounding fatty tissues and organs from intervening between the
      anastomosis planes and consequently guided an accurate and safe anastomosis.
      Neither anastomotic-related nor pancreatic-related complication was observed in
      this series. CONCLUSIONS: This anastomotic technique should be useful as an easy
      and safe reconstruction method in LADG and is especially recommendable for less
      experienced laparoscopic gastric surgeons.

PMID- 19851244
TI  - Double percutaneous endoscopic gastrojejunostomy tubes for decompression and
      refeeding together with enteral nutrients: three case reports and a review of the
      literature.
AB  - Percutaneous endoscopic gastrostomy had become a general technique for placement
      of indwelling feeding and decompressive tubes. There have been few reports that
      double percutaneous endoscopic gastrojejunostomy (PEGJ) tubes for decompression
      and refeeding together with enteral nutrients. We herein present 3 cases,
      characterized by chronic malnutrition and requiring long-term digestive
      decompression and enteral nutritional support, which were placed in double PEGJ
      tubes under endoscopic or fluoroscopic guidance. The procedures were successfully
      completed for all the patients. Two patients resumed oral intake and PEGJ tubes
      were removed. The second patient was provided home enteral nutrition while
      waiting for surgery. Three unusual cases were successfully treated by double PEGJ
      tubes for digestive decompression and refeeding together with enteral nutrients.

PMID- 19851245
TI  - A comparative study of the long-term outcomes after laparoscopy-assisted and open
      left lateral hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND: Laparoscopic hepatectomy was initially reported in 1992. However, the
      reported experiences are scarce, and this operation has not been a standard
      procedure until now. The aims of this study were to assess our results of
      laparoscopy-assisted left lateral hepatectomy for hepatocellular carcinoma (HCC)
      and to compare them with those of open conventional procedures. METHODS: From
      1984 to 2002, left lateral hepatectomy for HCC less than 5 cm in diameter was
      carried out in 21 patients. Ten patients received a laparoscopy-assisted
      procedure, and remaining 11 patients received an open procedure. RESULTS: There
      were no significant differences in the operation time, blood loss, resected liver
      weight, and resection margin between the 2 groups. The total time that analgesics
      were given, body temperature on postoperative day 1, weight loss on postoperative
      day 7, and postoperative hospital stay in the laparoscopic group were
      significantly better than in the conventional group. With regard to the long-term
      prognosis, there were no differences in patient survival or disease-free survival
      rates between the 2 groups. CONCLUSIONS: Laparoscopy-assisted left lateral
      hepatectomy for HCC is superior to the conventional open surgery in terms of its
      short-term results and does not cause the long-term survival to deteriorate.
      Therefore, laparoscopic hepatectomy may be an alternative choice for treatment of
      HCC.

PMID- 19851246
TI  - Transecting the pancreas neck with electrothermal bipolar vessel sealer
      (LigaSure) in laparoscopic left pancreatectomy: case report.
AB  - BACKGROUND: Pancreatic fistula after distal pancreatectomy remains an unsolved
      problem, ranging in frequency between 15% and 40%, regardless of whether the
      intervention is performed laparoscopically or by open surgery. METHODS: Herein,
      presenting the case of a 68-year-old woman with a functioning insulinoma
      submitted to laparoscopic spleen preserving distal pancreatectomy, we propose a
      new technique of pancreatic transection by the LigaSure system, which seals
      vessels and other tubular structures by reforming parietal collagen and elastin.
      RESULTS: The patient had a favorable outcome. The reported technique presents the
      advantages of an easy employ and of a contemporary hemostasis, thus being
      particularly suitable by the laparoscopic way, and may offer from a theoretical
      point of view some advantages over conventional pancreatic stump closure
      techniques in terms of fistula formation. CONCLUSIONS: Laparoscopic pancreatic
      transection by LigaSure may prove useful, safe, and effective. A prospective
      clinical study has now been designed to confirm such hypothesis. SHORT SUMMARY: A
      simple and safe technique for pancreas neck transection, particularly suitable
      for laparoscopic left pancreatectomy, is described.

PMID- 19851247
TI  - A hybrid technique for recurrent incisional hernia repair.
AB  - PURPOSE: The aim of this technical report is to investigate the safety and
      effectiveness of a hybrid technique for recurrent incisional hernia repair, which
      combines the conventional and laparoscopic approaches. METHODS: Six patients
      suffering from recurrent and complicated incisional hernias underwent a hybrid
      technique for their repair. The open part of the operation ensured extensive and
      safe adhesiolysis, reduction of the hernia content into the peritoneal cavity,
      and proper placement of the bowel loops into the peritoneal cavity, minimizing
      the risk of bowel perforation. For the laparoscopic part of the procedure,
      intraperitoneal (underlay) e-PTFE mesh placement, of the appropriate size
      covering the actual hernia size and the scar edges for at least 3 cm, was
      laparoscopically fixated by transfascial stay stitches, allowing stretch of the
      mesh on the anterior abdominal wall, probably avoiding the mesh deformation in
      the future. RESULTS: The overall size of the fascial defect was calculated
      between 116 and 187 cm, the size of the mesh used ranged from 308 to 468 cm, the
      total operative time ranged from 128 to 207 minutes and within a maximum follow
      up period of 12 months, all patients are asymptomatic without any evidence of
      hernia recurrence. CONCLUSIONS: The hybrid technique is safe in cases of
      recurrent or complicated or difficult incisional hernias. A longer follow-up
      period is required to estimating the effectiveness and the cost-effectiveness of
      the method.

PMID- 19851248
TI  - An easy technique for laparoscopic placement of Seprafilm.
AB  - The use of antiadhesive sheets has greatly reduced the number of postoperative
      adhesions after abdominal surgery. A major problem is that these sheets are
      difficult to deliver into the peritoneal cavity because they are not malleable
      and easily stick when wet. This article describes a simple technique for
      administering Seprafilm sheets onto the abdominal viscera after laparoscopic
      surgery. The Seprafilm sheets are dissolved before the end of surgery in warm
      normal saline and the solution is placed into a Toumey catheter tip syringe. The
      syringe is then attached to a Robinson catheter, which is introduced into the
      abdomen via a laparoscopic trocar. Under direct laparoscopic visualization, the
      Seprafilm solution is squirted into the damaged peritoneal surfaces. Long-term
      studies are needed to assess whether our Seprafilm solution technique has the
      same efficacy as the use of whole sheets.

PMID- 19851249
TI  - Epiphrenic diverticulum: robotic-assisted transhiatal approach.
AB  - Surgery of the epiphrenic diverticulum has been related to high postoperative
      morbidity. Even through a minimally invasive approach, dissection of the neck
      proximal portion of the diverticulum can be difficult. Robotic-assisted (RA)
      technologies have been developed recently. We describe our experience of RA
      transhiatal diverticulectomy in 2 patients: (1) A 73-year-old female patient who
      presented with 2 large esophageal diverticula at the mid esophagus and
      gastroesophageal junction, and a large hiatal hernia. A RA transhiatal
      diverticulectomy and Nissen fundoplication were performed, although intense
      adhesions made a limited thoracotomy necessary. The patient developed a mild
      esophageal leak, which resolved successfully with conservative treatment; (2) A
      63-year-old male patient with a large epiphrenic diverticulum, which was resected
      using the RA transhiatal approach, and a Toupet fundoplication was also
      performed. The postoperative course was uneventful. We believe that RA
      transhiatal management of epiphrenic diverticulum can help during the dissection
      of the proximal portion of the diverticulum and might reduce postoperative
      morbidity.

PMID- 19851250
TI  - Laparoscopic surgical treatment for refractory gastric antral vascular ectasia: a
      case report and review.
AB  - Gastric antral vascular ectasia (GAVE) is an angiodysplastic disorder of unclear
      etiology and rare cause of upper gastrointestinal bleeding. Endoscopic findings
      of hyperemic antral folds with dilated, tortuous vessels extending radially from
      the pylorus are diagnostic. Ectatic submucosal capillaries, microvascular fibrin
      thrombosis, and fibromuscular hyperplasia in the lamina propria are distinctive
      histologic features. Diverse treatment options are available, ranging from
      conservative medical or endoscopic therapy to surgical resection of affected
      gastric region. Surgery is the only known curative treatment and is traditionally
      pursued after failure of conservative therapy, as high postoperative mortality
      has been reported. A case of refractory GAVE in a 71-year-old female patient
      after 5 years of conservative management, is presented. The patient underwent
      successful laparoscopic distal gastrectomy and gastrojejunostomy with resolution
      of symptomatic anemia and melena. Clinical findings, diagnosis, etiology, and
      treatment of GAVE are reviewed here, with discussion of safety and efficacy of
      laparoscopic gastric resection for its treatment.

PMID- 19851251
TI  - The dangers of using stapling devices for cystic duct closure in laparoscopic
      cholecystectomy.
AB  - Laparoscopic stapling devices are used widely in laparoscopic surgery, for
      division of vessels and creation of anastomoses. Their use in the division of a
      widened cystic duct at laparoscopic cholecystectomy has been reported earlier. We
      present 3 different complications occurring after division of the cystic duct
      using the EndoGIA stapling device. A review of the literature has been performed
      and safe alternative techniques for laparoscopic ligation of the cystic duct are
      proposed.

PMID- 19851252
TI  - Terlipressin in control of acute hemobilia during therapeutic ERCP in patient
      with portal biliopathy.
AB  - BACKGROUND: Portal biliopathy is a late and serious complication of extrahepatic
      portal venous obstruction usually manifesting with jaundice. Surgery and
      endoscopic therapy are the usual modalities of treatment for this condition.
      Endoscopic management contains inherited risk of hemobilia treatment of which is
      yet to be standardized. PATIENTS AND METHODS: Retrospective analysis of data from
      2002 to 2007 for nonsurgical management of portal biliopathy was carried out. We
      encountered 4 cases of hemobilia during this period. The management and outcome
      of these 4 patients was analyzed. RESULTS: Median age at presentation was 39
      years (22 to 50 y). All the patients had cholestatic jaundice and pain as
      presenting symptoms without prior history of gastrointestinal bleed. The median
      serum bilirubin and alkaline phosphatase values were 5 mg/dL (4.8 to 11.3 mg/dL )
      and 494 IU/mL (342 to 645 IU/mL), respectively. Endoscopic retrograde
      cholangiography documented changes of portal biliopathy along with
      choledocholithiasis in all the 4 patients. An uneventful endoscopic
      sphincterotomy was followed by significant hemobilia during attempted stone
      extraction by Dormia basket/balloon. Patients were resuscitated with standard
      measures and injection terlipressin was started at a dose of 1 mg 4 times daily.
      Control of bleeding was achieved within 12 hours of infusion in all 4 patients
      and there was no bleed-related mortality. CONCLUSIONS: All our patients had
      symptomatic portal biliopathy as their first manifestation of underlying
      extrahepatic portal venous obstruction. Common bile duct stone extraction in
      patients with portal biliopathy carries a high risk of hemobilia even with
      balloon sweeping. Terlipressin is an effective pharmacologic treatment for
      hemobilia in patients with portal biliopathy.

PMID- 19851253
TI  - Placement of stents in proximal colonic obstructions using a percutaneous
      retroperitoneal colostomy.
AB  - In cases of proximal colonic obstruction, the long distances and the tortuosity
      of the distal bowel make it difficult to advance and position the stent in the
      target lesion. We report 2 cases of stent placement for malignant obstruction of
      the proximal colon in which access was obtained through percutaneous
      retroperitoneal colostomy. In these cases, we initially tried to place a stent
      through the rectum under endoscopic guidance, but it was not possible to reach
      the lesion. We then decided to cross the lesion through percutaneous puncture of
      the retroperitoneum. The procedures were completed without complications and the
      patients' symptoms improved. A percutaneous retroperitoneal approach for the
      deployment of colonic stents has not been described earlier in the literature. We
      suggest that our technique provides an alternative means of colonic decompression
      in cases in which conventional retrograde methods fail to provide acceptable
      palliation in nonsurgical candidates.

PMID- 19851254
TI  - Rectal bleeding in Klippel-Trenaunay syndrome: treatment with laparoscopic
      ultralow anterior resection with intersphincteric dissection.
AB  - Klippel-Trenaunay syndrome is a rare congenital vascular disorder characterized
      by varicose veins, hypertrophy of the soft tissues and bones, and hemangiomas.
      Although colorectal angiomatosis is uncommon, this association can lead to life
      threatening complications because of acute or chronic bleeding. We report a
      patient with Klippel-Trenaunay syndrome who presented with transfusion-dependent
      anemia secondary to chronic rectal bleeding. Endoscopy and image studies revealed
      venous angiomata involving the rectum and distal sigmoid colon. We performed a
      laparoscopic ultralow anterior resection with intersphincteric dissection,
      obtaining good results. After a follow-up of 20 months the patient did not
      present hematochezia and maintained fecal continence.

PMID- 19851255
TI  - A rare complication of laparoscopic low anterior resection.
AB  - We report a 70-year-old lady who suffered from carcinoma of rectum with the
      lowest border of the tumor at 5 cm from the anal verge. Preoperative staging did
      not show any distant metastasis. Laparoscopic low anterior resection with total
      mesorectal excision was performed. The rectum was transected with endoscopic
      stapler and a double stapling anastomosis with a circular stapler was attempted.
      The spear of the circular stapler pierced through the rectal stump and attempt to
      remove the spear by pulling the suture attached to the spear failed. A pair of
      strong laparoscopic forceps was used in an attempt to remove the spear. The spear
      broke during the attempt of removal. The stapler was withdrawn through the anus
      with a pair of laparoscopic forceps following it. A new circular stapler was used
      and the tip was tied to a suture and cotton tape. The pair of forceps, which was
      still at the anus, was used to pull the cotton tape and the suture through the
      original perforation at the rectal stump. The tip of the spear of the new stapler
      was guided through the original perforation of the rectal stump. Double stapling
      was then performed and the patient recovered uneventfully. This case showed that
      stapler complication in laparoscopic surgery could be salvaged without
      conversion.

PMID- 19851256
TI  - Acute lower gastrointestinal bleeding due to appendiceal mucosal erosion.
AB  - Acute lower gastrointestinal hemorrhage associated with the appendix is rare. We
      report on a 42-year-old male patient who presented with hematochezia from
      solitary appendiceal bleeding. The patient was admitted to our hospital with
      rectal bleeding, and abdominal computed tomography identified active contrast
      leakage in the distal portion of the appendix. During a subsequent urgent
      colonoscopy, active bleeding in the appendiceal orifice was identified. The
      patient was successfully treated with a laparoscopic appendectomy and
      hematochezia did not recur postoperatively. Microscopic examination revealed an
      eroded appendiceal mucosa, focal inflammatory infiltrates, and a normal
      submucosal vessel without evidence of vascular malformation.

PMID- 19851257
TI  - Laparoscopic treatment of hydatid cyst of the spleen without splenectomy: report
      of a case.
AB  - Laparoscopic surgery is going to be the first-line operative technique for a
      variety of benign spleen lesions in selected patients. The anatomic location of
      the lesions is more important than another peculiarity in the laparoscopy. A 38
      year-old woman presented with left-sided abdominal discomfort. Radiologic
      evaluation revealed a 6 x 7 hydatid cyst in spleen. The patient underwent
      laparoscopic spleen-preserving cystotomy and omentoplasty for the lesion. She was
      discharged on the second day of operation uneventfully. The aim of the study is
      to investigate the effects and feasibility of laparoscopic management of hydatid
      cyst of the spleen. The procedure was shown to be feasible and safe, offering the
      advantages of laparoscopic surgery.

PMID- 19851258
TI  - Laparoscopic examination and resection for giant lipoma of the omentum: a case
      report and review of related literature.
AB  - We report herein the case of a giant lipoma of the greater omentum that was
      treated by laparoscopic surgery. A 71-year-old male patient was admitted with a
      diagnosis of sigmoid colon cancer. During preoperative examination, a gallbladder
      stone and an intra-abdominal giant lipoma were accidentally diagnosed.
      Laparoscopic examination revealed a smooth-surfaced, giant yellow tumor at the
      lower border of the greater omentum that was unattached to the surrounding
      organs. After laparoscopic resection of the tumor and cholecystectomy, a 10-cm
      midline incision was made in the lower abdomen to remove the tumor and the
      gallbladder. We then performed a sigmoidectomy for sigmoid colon cancer through
      the same laparotomy. The resected tumor measured 29 x 19 x 3 cm and weighed 1250
      g, and a histopathologic examination revealed a benign lipoma. Laparoscopic
      examination and resection of a giant lipoma of the omentum are particularly
      useful.

PMID- 19851259
TI  - Laparoscopic excision of an epidermoid cyst arising from the deep abdominal wall.
AB  - Epidermoid cysts are the most common type of cutaneous cyst. However, their
      occurrence in the deep abdominal wall has not yet been reported. Here, we present
      the case of a 60-year-old woman who developed an epidermoid cyst in the deep
      abdominal wall, which was resected laparoscopically. The patient presented with
      right upper quadrant abdominal pain on admission to our hospital. Computed
      tomography revealed cholecystolithiasis and an incidentally identified well
      defined hypoattenuating mass (62 x 47 x 65 mm) in the deep abdominal wall on the
      left side of the navel. We performed laparoscopic complete resection of the
      abdominal wall tumor followed by cholecystectomy. The excised specimen was a cyst
      covered with a smooth thin membrane and contained sludge. Histopathologic
      examination revealed an epidermoid cyst. This is a very rare case with no
      previous reports on a similar type of epidermoid cyst.

PMID- 19851260
TI  - Heterotopic gastric mucosal patch in patients with reflux laryngitis: an entity
      of clinical interest?
AB  - Heterotopic gastric mucosal patch (HGMP) in the upper esophagus has been
      suggested to play a role in the pathogenesis of laryngopharyngeal reflux. The aim
      of this study was to evaluate the prevalence and possible clinical significance
      of HGMPs in patients who underwent laparoscopic Nissen fundoplication for
      gastroesophageal reflux disease-induced reflux laryngitis.Forty consecutive
      patients with pH-proven reflux laryngitis referred to surgery by a specialist in
      otorhinolaryngology underwent laparoscopic Nissen fundoplication between 1998 and
      2002. Twenty-seven (67.5%) of these patients underwent a postoperative upper
      gastrointestinal endoscopy paying special attention for detecting possible HGMPs
      in the proximal esophagus. When HGMP was found, biopsies were taken for
      histologic confirmation. A small histologically confirmed HGMP was detected in 1
      out of 27 patients (3.7%). The prevalence of HGMPs in the upper esophagus in this
      specific patient group operated on for gastroesophageal reflux disease-induced
      reflux laryngitis equals the reported general prevalence rates of HGMPs detected
      in patients referred for upper gastrointestinal endoscopy as a part of
      gastrointestinal tract evaluation. The role of at least small HGMPs in the
      proximal esophagus in the pathogenesis of laryngopharyngeal reflux is clinically
      insignificant.

PMID- 19851261
TI  - Palliative management of esophagorespiratory fistula in esophageal malignancy.
AB  - INTRODUCTION: Esophagorespiratory fistula (ERF) is a complication of an
      esophageal malignancy that has serious effects on the mortality of a patient,
      whose survival is limited to weeks. Sealing of fistula and recovery of swallowing
      has greater importance than treating underlying primary malignancy. In this
      study, we aimed to present our clinic experience in patients with ERF and to
      discuss the findings together with the literature. MATERIALS AND METHODS: Between
      January 2003 and December 2008, 326 patients with malignant esophageal disorder
      were admitted to our clinic, and ERF detected in 18 (5.5%) patients. There were
      10 men and 8 women with a mean age of 54.7+/-11.9 years (range: 34 to 75 y).
      Metastases in the lung and liver were detected in 4 and 2 patients, respectively.
      Empyema was found in 3 of the ERF patients. Pneumonic infiltration was detected
      via radiologic evaluation in 7 (38.9%) of the 18 patients. Two patients did not
      accept any intervention. A feeding gastrostomy tube was placed in 2 other
      patients. Fluoroscopy-guided Ultraflex esophageal stent placement was applied to
      the remaining 14 patients. Eleven (78.6%) patients underwent stent placements
      during generalized anesthesia via rigid esophagoscopy, and the remaining 3
      (21.4%)patients via flexible esophagoscopy with sedation. RESULTS: One of the
      patients who did not accept intervention died after 2 weeks, and the other died 6
      weeks after admission. One of the patients who received a feeding gastrostomy
      tube died 17 weeks after admission, and the other was still alive after a month,
      when this article was written. Closure of the ERF was seen in all 14 patients who
      underwent palliative covered self-expandable metallic stent placement in the
      esophagus. No complications occurred in the stent-placed patients either during
      or after the procedure. Dyspeptic complaints and pain were treated successfully
      with medical therapy in 6 and 5 patients, respectively. Symptoms of aspiration
      disappeared after stent placement. No reopened fistulae were observed during
      follow-up. Thirteen of the 14 stent-replaced patients died during follow-up. The
      mean survival rate for these 13 patients was 11.2 weeks (range: 1 to 49 wk). The
      mean length of hospital stay after stent placement in the 14 patients was 3.7
      days (1 to 15 d). DISCUSSION: Covered self-expandable metallic stent placement in
      malign ERF patients is a technically simple and safer method for fistula closure
      and seems to be the most effective method that is easily available.

PMID- 19851262
TI  - Needlescopic clipless cholecystectomy as an efficient, safe, and cost-effective
      alternative with diminutive scars: the first 1000 cases.
AB  - BACKGROUND: The advent of natural orifice transluminal endoscopic surgery (NOTES)
      and single-incision laparoscopic surgery (SILS), surgery without skin scarring,
      is now challenging every surgeon to improve the esthetic results for patients.
      Minilaparoscopic cholecystectomy (MLC) represents a refinement in laparoscopic
      surgery, potentially as cosmetically effective as NOTES. Nevertheless, because of
      the increased cost and difficulty in managing the equipment, it has not been
      widely accepted among surgeons. OBJECTIVE: To report modifications of the
      minilaparoscopic technique that make it possible to conduct needlescopic
      procedures safely and effectively, thereby, considerably reducing costs and
      promoting the dissemination of this operation. METHOD: One thousand consecutive
      patients who underwent MLC were analyzed, from January 2000 to May 2009 (78.7%
      women; average age 45.9 y). SURGICAL TECHNIQUE: after performing the
      pneumoperitoneum at the umbilical site, 4 trocars were inserted; 2 of 2 mm, 1 of
      3 mm, and 1 of 10 mm in diameter, through which a laparoscope was inserted.
      Neither the 3-mm laparoscope, nor clips, nor manufactured endobags were used. The
      cystic artery was safely sealed by electrocautery near the gallbladder neck and
      the cystic duct was sealed with surgical knots. Removal of the gallbladder was
      carried out, in an adapted bag made with a glove wrist, through the 10-mm
      umbilical site. RESULTS: The operative time was 43 minutes. The average hospital
      stay was 16 hours. There was no conversion to open surgery; 2.8% of patients
      underwent conversion to standard (5 mm) laparoscopic cholecystectomy because of
      difficulties with the procedure; there were 1.9% minor umbilical site infections
      and 1.0% umbilical herniations. There was no mortality; no bowel injury, no bile
      duct injury, and no postoperative hemorrhage, only 1 patient with Luschka's duct
      bile leakage needed a reoperation. CONCLUSIONS: The MLC technique shows no
      differences in risks as compared with other laparoscopic cholecystectomy
      procedures. It also entails a considerable reduction in cost, and, as it does not
      use the 3-mm laparoscope or disposable materials, it is possible to perform MLC
      on a larger number of patients. Owing to the near invisibility of scars, MLC may
      also be considered as cosmetically effective as NOTES and SILS.

PMID- 19851263
TI  - Effects of previous abdominal surgery incision type on complications and
      conversion rate in laparoscopic cholecystectomy.
AB  - For laparoscopic cholecystectomy, previous abdominal operations are seen as a
      relative contraindication. The purpose of this study was to investigate the
      effects of the incision type of previous abdominal surgery on laparoscopic
      cholecystectomy in terms of complications and conversion to open surgery. Data
      from 677 patients who had previously undergone abdominal surgery before
      undergoing laparoscopic cholecystectomy were prospectively collected and
      evaluated. From the previous operations, the incisions were upper abdominal in 66
      patients, lower abdominal in 567, and upper plus lower in 44. Conversion rates in
      the upper, lower and upper plus lower groups were 27.27%, 2.82%, and 25%,
      respectively. Intraoperative major complications were bile duct injury (1
      patient, upper plus lower incision group), small bowel mesentery injury, and
      aortic injury (1 patient each, both in the lower incision group). Postoperative
      major intra-abdominal complications were duodenal injury (1 patient, upper
      incision group) and small intestine injury (1 patient, lower incision group). The
      lower abdominal incision group had fewer adhesions in the upper abdomen than did
      the other 2 groups, and as a result had a much lower conversion rate.

PMID- 19851264
TI  - Bile leaks after cholecystectomy: the significance of patient selection.
AB  - OBJECTIVE: A retrospective analysis of laparoscopic and open cholecystectomies,
      with introduction of selection criteria and estimation of postoperative bile
      leaks. METHOD: All patients who underwent cholecystectomy in a tertiary surgical
      unit from January 2007 to June 2008 formed 2 categories, laparoscopic and open.
      The choice of operation was based on patient's present status and past medical
      history, whereas the decision to convert came from intraoperative findings. All
      surgeons were experienced in both open and laparoscopic surgeries. RESULTS:
      Laparoscopic cholecystectomy was initially attempted in 230 patients. In 218 of
      these patients, cholecystectomy was accomplished laparoscopically (group A),
      whereas in 12 laparoscopic was converted to open cholecystectomy (group B). In 36
      patients open cholecystectomy was the first choice according to predecided
      criteria (group C). Patients of groups B and C were older (P=0.0001), presented
      higher incidence of cholecystitis (P=0.0001), and required longer postoperative
      hospitalization (P=0.0001) compared with patients of group A. Postoperative bile
      leak was evident in 8 patients; no patient from group A, 2 patients from group B,
      and 6 patients from group C. Patients with bile leak were older (P=0.0001), they
      required a longer hospitalization (P=0.0001), and cholecystitis was more frequent
      (P=0.007). Regarding treatment followed, 4 patients required no intervention,
      whereas 1 required computed tomography-guided drainage of a biloma. Two patients
      with persistent bile leak, required stenting of the common bile duct with
      endoscopic sphincterotomy, whereas one, suffering from common bile duct injury,
      was cured with hepatojejunostomy. CONCLUSIONS: The study highlights the
      significance of patient selection based on clinical criteria with respect to the
      type of operation performed. It seems that when patients are selected for
      laparoscopy according to carefully chosen criteria, the expected postoperative
      bile leaks could be minimal.

PMID- 19851265
TI  - Laparoscopic gastrectomy for gastric cancer.
AB  - BACKGROUND: Surgery in gastric cancer (GC) aims to achieve resection of the
      primary tumor and its lymphatic drain, with a minimal adverse effect on morbidity
      and mortality, and the best possible quality of life. METHODS: From June 1993 to
      May 2008, 113 patients with a preoperative diagnosis of the GC were considered
      for laparoscopic gastrectomy at our institution. There was a predominance of
      males and mean age was 60 years. After peritoneal cavity inspection, laparoscopic
      ultrasound was used to determine the presence of deep liver metastasis. Total
      gastrectomy and Roux-en-Y reconstruction were performed in upper and middle-third
      tumors, and subtotal gastrectomy, either with Billroth II or Roux-en-Y
      reconstruction, in tumors affecting the lower third of the stomach. D2
      lymphadenectomy was performed in both cases. RESULTS: There were 21 cases (18.5%)
      with distant metastases and/or an unresectable tumor due to the invasion of
      adjacent organs. In these patients the procedure was limited to laparoscopic
      biopsy in 16 cases and laparoscopic gastrojejunostomy in 5 cases. Laparoscopic
      gastrectomy was performed in 92 patients with a mean surgical time of 162 minutes
      and a mortality rate of 5.4%. Conversion was necessary in 7 cases (7.6%).
      CONCLUSIONS: The benefits and safety of laparoscopic gastrectomy are evident,
      with similar outcomes to conventional surgery and all the advantages of minimally
      invasive access. The learning curve is long. Laparoscopic gastrectomy is a safe
      and effective option for the treatment of GC, avoiding nontherapeutic laparotomy
      in patients with advanced disease. Comparative prospective studies evaluating the
      long-term survival of these patients are still necessary.

PMID- 19851266
TI  - Laparoscopic resection for liver tumors: initial experience in a single center.
AB  - BACKGROUND: Laparoscopic liver resections are 1 of the most complex procedures in
      hepatobiliary surgery. During the last 20 years, laparoscopic liver surgery has
      had an important development in specialized centers. OBJECTIVE: To describe the
      initial experience in laparoscopic liver resection for benign and malignant
      tumors, to assess its indications and outcomes, and to describe technical aspects
      of these resections. METHODS: Review of the records of 28 patients who underwent
      laparoscopic liver resection between November 2000 and November 2007. Analysis of
      the data regarding preoperative management and postoperative outcomes. RESULTS:
      Twenty-six liver resections were performed laparoscopically (20 purely
      laparoscopic, 3 hand assisted, and 3 hybrid technique) and 2 were converted to
      open surgery. The laparoscopic approach was attempted in 6% (28 out of 459) of
      the liver resections carried out in the analyzed period. Indications for
      resection were: benign tumors in 22 patients (78%) and malignant tumors in 6
      patients (22%). Resections were minor in 27 patients (96%) and major in 1 patient
      (4%). Pringle maneuver was performed in 14 patients (50%). Margins were negative
      in all the cases. Mean operative time was 170 minutes (range 70 to 350), and the
      mean length of stay was 3 days (range 1 to 6). Mortality rate was 0%. Only 2
      patients (7%) had postoperative minor complications (self-limited bile leaks).
      CONCLUSIONS: In selected patients with benign and malignant liver tumors,
      laparoscopic liver resections can be safely performed. This procedure must be
      carried out by the surgeons trained in both the hepatobiliary and laparoscopic
      surgery.

PMID- 19851267
TI  - Should the macroscopically normal appendix be removed during laparoscopy for
      acute right iliac fossa pain when no other explanatory pathology is found?
AB  - BACKGROUND: Acute appendicitis remains the most common surgical emergency and
      although diagnosis should be made on clinical grounds, sometimes this can be
      difficult. Laparoscopy has gained increasing favour as a method of both
      investigating right iliac fossa pain and treating the finding of appendicitis.
      The aim of this study was to determine the accuracy of intraoperative diagnosis
      of appendicitis. PATIENTS AND METHODS: Records of all patients who underwent
      laparoscopy for possible appendicitis at the Norfolk and Norwich University
      Hospital over a 1-year period were reviewed. Notes of those patients who
      underwent an open appendicectomy were also reviewed for comparison.
      Intraoperative findings were recorded, as were the subsequent pathologic
      findings. RESULTS: Over the 1-year period from September 2005 to September 2006,
      355 operations for suspected appendicitis were performed. In 277 (78%) cases,
      these were performed laparoscopically. Seventy-three out of 78 open
      appendectomies were confirmed as appendicitis. Only 1 of these was not
      macroscopically evident to the surgeon. The appendix was removed in 259 of the
      277 laparoscopic procedures. Correct intraoperative diagnosis was made in 217
      (84%) of removed appendices, 12 (29%) of the appendices thought to be
      macroscopically normal and removed were found to be appendicitis after histologic
      examination. Eighteen patients undergoing the laparoscopic procedure had their
      appendix left in situ due to normal appearance; none had represented at 6 months
      postsurgery. CONCLUSIONS: Laparoscopy may aid in the diagnosis of acute right
      iliac fossa pain. However, intraoperative diagnosis is not easy with almost one
      third of apparently normal appendices being inflamed histologically. We would
      therefore advocate the removal of a normal looking appendix in the absence of
      other explanatory pathology.

PMID- 19851268
TI  - Re: Should the macroscopically normal appendix be removed during laparoscopy for
      acute right iliac fossa pain when no other explanatory pathology is found?

PMID- 19851270
TI  - Analysis of laparoscopic colorectal surgery in high-risk patients.
AB  - The aim of this retrospective study is to examine the feasibility and safety of
      laparoscopic colorectal resection for colorectal malignancies to determine "high
      risk" patients. In our classification, 3 minor criteria including patients over
      70 years of age, body mass index over 30 m/kg, and cigarette smoking and 5 major
      criteria including cardiac, pulmonary, renal, liver disease, and diabetes
      mellitus were selected to determine a high-risk group. Patients carrying 1 minor
      and 1 major criteria were classified as the high-risk group. Concerning patients
      and operations, hemodynamic values (mean arterial systolic and diastolic
      pressures and heart rates), oxygen saturations, end-expiratory carbon dioxide
      levels, respiratory mechanics (dynamic compliance, peak inspiratory pressure,
      airway resistance) were analyzed. Cardiovascular system (myocardial infarction,
      arrhythmia, hypertension), pulmonary system (respiratory insufficiency),
      digestive system (anastomotic leak, fistula, and paralytic ileus), fever,
      thrombophlebitis, urinary infections, wound infections, and central nervous
      system (delirium and cerebrovascular accident) were also investigated. A total
      number of 85 high-risk patients were included in the study. Gastrointestinal
      leaks in 2.3%, fistula in 1.1%, ileus in 3.5%, postoperative bleeding in 2.3%,
      postoperative fever in 5.8%, wound infection in 5.8%, and cerebrovascular
      accidents in 1.1% of patients were detected. The lowest values of hemodynamic and
      respiratory mechanics were observed at the induction of pneumoperitoneum and in
      this period the compliance and mean arterial pressure were determined to be 36+/
      14 mm Hg and 84+/-14 mm Hg, respectively. No mortalities occurred. In experienced
      hands, laparoscopic colorectal resection can be performed safely for "high-risk"
      surgical patients.

PMID- 19851271
TI  - Body image and cosmesis after laparoscopic or open appendectomy.
AB  - INTRODUCTION: Minimally invasive techniques, such as laparoscopic appendectomy
      (LA), are thought to produce better cosmetic results. The aim of this study was
      to evaluate the body image and cosmesis of patients after both LA and open
      appendectomy (OA). PATIENTS AND METHODS: Between August 2007 and June 2008,
      patients who underwent LA or OA with the diagnosis of acute appendicitis were
      invited to participate in the study by filling out the body image questionnaire.
      Patients with OA who had the Rockey-Davis incision and LA patients who had the
      operation by 3 trocars (10-mm infraumbilical, 5-mm suprapubic and additional 10
      mm left lower quadrant), were included in the study. RESULTS: A total of 38
      patients (20 LA, 18 OA) participated in the study. The mean incision size for OA
      was 3.2 cm (range, 2 to 6 cm), and the mean scores from the body image
      questionnaire (both body image scale and cosmetic scale) were similar for both
      groups (P>0.05). No significant complications or changes in self-confidence
      (preoperative vs. postoperative) were observed in either group (P>0.05).
      CONCLUSIONS: To our knowledge, there is no study in the literature that evaluates
      body image and cosmesis using objective methods for LA. Our results showed that
      LA has no advantage for body image and cosmesis over OA. Furthermore, prospective
      studies using different tools with a larger sample size are needed to rationalize
      the use of laparoscopy for appendectomy.

PMID- 19851272
TI  - Patient satisfaction, hernia recurrence rate, and chronic pain 10 years after
      endoscopic total extraperitoneal inguinal hernia repair.
AB  - INTRODUCTION: Long-term outcome data after total endoscopic preperitoneal hernia
      repair are scarce. This study reports the 10-year results after endoscopic total
      extraperitoneal hernia repair in terms of recurrence rates and various patient
      orientated indicators of quality of life. METHODS: Between July 1995 and April
      2000, 107 consecutive patients underwent endoscopic total extraperitoneal
      inguinal hernia repair. The follow-up assessment between December 2007 and June
      2008 included a clinical examination and a patient questionnaire. RESULTS: Sixty
      three patients (64.3%) with 108 hernias attended follow-up, an average of 115.7
      months (range 91 to 148 mo) after the index operation. The incidence of
      recurrence was 2.8%, of chronic pain 15.9%, and of foreign body sensation 33.3%.
      Patient satisfaction measured on the Visual Analogue Scale was high with a median
      of 9.6 (range 0.3 to 10). CONCLUSIONS: Endoscopic total extraperitoneal hernia
      repair is a safe and effective procedure with excellent long-term results and an
      extremely high rate of patient satisfaction.

PMID- 19851273
TI  - Laparoscopic vesico-vaginal fistula repair: our experience and review of the
      literature.
AB  - PURPOSE: To describe our experience with laparoscopic transperitoneal vesico
      vaginal fistula (VVF) repair and we review current literature. METHODS: Four
      patients with VVF underwent transperitoneal transvesical laparoscopic repair,
      with the same principles of open abdominal approach. We considered: operation
      time, complications, hospital stay, Foley catheter duration, and recurrence
      during the follow-up. RESULTS: Mean operative time was 103 minutes and no
      complications were recorded. Average length of hospital stay was 3 days, Foley
      catheter remained indwelling on an average of 8 days. All patients were cured,
      after a mean of 14.5 months no recurrence was recorded and no patient referred
      urinary symptoms. CONCLUSIONS: On the basis of our and literature data, we
      believe that laparoscopic VVF repair is feasible, safe and effective and it is a
      viable alternative to the traditional open procedure.

PMID- 19851274
TI  - Duration and clinical significance of radiographically detected "free air" after
      laparoscopic nephrectomy.
AB  - The purpose of this study was to evaluate the duration and clinical significance
      of postoperative pneumoperitoneum (PP) after laparoscopic nephrectomy. We
      reviewed consecutive laparoscopic nephrectomies from 2001 to 2007. The presence
      and timing of free intraperitoneal air was documented. Postoperative imaging was
      performed in 135 of 538 patients with 55 patients (41%) noted to have free air.
      These included 53 hand-assisted laparoscopic nephrectomies and 2 purely
      laparoscopic radical nephrectomies. There was no difference between patients with
      and without PP with respect to age, sex, race, length of hospital stay (LOS),
      operating room time, earliest postoperative film with PP, presence of free air on
      plain film, or complication rate (P>0.05). Donor nephrectomy patients had the
      highest incidence of PP (P=0.01). Nineteen patients had benign PP (34.5%) at
      least 3 days after surgery with the longest interval postsurgery being 9 days.
      Postoperative free air after laparoscopic nephrectomy is common, even up to 9
      days after surgery.

PMID- 19851275
TI  - Advice for travelers.

PMID- 19851276
TI  - Isolation and derivation of mouse embryonic germinal cells.
AB  - The ability of embryonic germinal cells (EG) to differentiate into primordial
      germinal cells (PGCs) and later into gametes during early developmental stages is
      a perfect model to address our hypothesis about cancer and infertility. This
      protocol shows how to isolate primordial germinal cells from developing gonads in
      10.5-11.5 days post coitum (dpc) mouse embryos. Developing gonadal ridges from
      mouse embryos (C57BL6J) were dissociated by mechanical disruption with
      collagenase, then plated in a mouse embryo fibroblast feeder layer (MEF-CF1) that
      was previously mitotically inactivated with mitomycin C in the presence of
      knockout media and supplemented with Leukemia Inhibitor Factor (LIF), basic
      Fibroblast Growth Factor (bFGF), and Stem Cell Factor (SCF). Using these
      optimized methods for PCG identification, isolation, and establishment of culture
      conditions permits long term cultures of EG cells for more than 40 days. The
      embryonic germinal cell lines showed embryonic phenotype and expression of common
      used markers of the pluripotent state. Isolation and derivation of germinal cells
      in culture provide a tool to understand their development in vitro and offer the
      opportunity to monitor cumulative damage at genetic and epigenetic levels after
      exposure to oxidative stress.

PMID- 19851278
TI  - Prenatal sex differences in the human brain.

PMID- 19851279
TI  - Stem cell signaling in newly diagnosed, antipsychotic-naive subjects with
      nonaffective psychosis.

PMID- 19851280
TI  - The LEARn model: an epigenetic explanation for idiopathic neurobiological
      diseases.
AB  - Neurobiological disorders have diverse manifestations and symptomology.
      Neurodegenerative disorders, such as Alzheimer's disease, manifest late in life
      and are characterized by, among other symptoms, progressive loss of synaptic
      markers. Developmental disorders, such as autism spectrum, appear in childhood.
      Neuropsychiatric and affective disorders, such as schizophrenia and major
      depressive disorder, respectively, have broad ranges of age of onset and
      symptoms. However, all share uncertain etiologies, with opaque relationships
      between genes and environment. We propose a 'Latent Early-life Associated
      Regulation' (LEARn) model, positing latent changes in expression of specific
      genes initially primed at the developmental stage of life. In this model,
      environmental agents epigenetically disturb gene regulation in a long-term
      manner, beginning at early developmental stages, but these perturbations might
      not have pathological results until significantly later in life. The LEARn model
      operates through the regulatory region (promoter) of the gene, specifically
      through changes in methylation and oxidation status within the promoter of
      specific genes. The LEARn model combines genetic and environmental risk factors
      in an epigenetic pathway to explain the etiology of the most common, that is,
      sporadic, forms of neurobiological disorders.

PMID- 19851281
TI  - Calreticulin-dependent recycling in the early secretory pathway mediates optimal
      peptide loading of MHC class I molecules.
AB  - Calreticulin is a lectin chaperone of the endoplasmic reticulum (ER). In
      calreticulin-deficient cells, major histocompatibility complex (MHC) class I
      molecules travel to the cell surface in association with a sub-optimal peptide
      load. Here, we show that calreticulin exits the ER to accumulate in the ER-Golgi
      intermediate compartment (ERGIC) and the cis-Golgi, together with sub-optimally
      loaded class I molecules. Calreticulin that lacks its C-terminal KDEL retrieval
      sequence assembles with the peptide-loading complex but neither retrieves sub
      optimally loaded class I molecules from the cis-Golgi to the ER, nor supports
      optimal peptide loading. Our study, to the best of our knowledge, demonstrates
      for the first time a functional role of intracellular transport in the optimal
      loading of MHC class I molecules with antigenic peptide.

PMID- 19851282
TI  - The helicases DinG, Rep and UvrD cooperate to promote replication across
      transcription units in vivo.
AB  - How living cells deal with head-on collisions of the replication and
      transcription complexes has been debated for a long time. Even in the widely
      studied model bacteria Escherichia coli, the enzymes that take care of such
      collisions are still unknown. We report here that in vivo, the DinG, Rep and UvrD
      helicases are essential for efficient replication across highly transcribed
      regions. We show that when rRNA operons (rrn) are inverted to face replication,
      the viability of the dinG mutant is affected and over-expression of RNase H
      rescues the growth defect, showing that DinG acts in vivo to remove R-loops. In
      addition, DinG, Rep and UvrD exert a common function, which requires the presence
      of two of these three helicases. After replication blockage by an inverted rrn,
      Rep in conjunction with DinG or UvrD removes RNA polymerase, a task that is
      fulfilled in its absence by the SOS-induced DinG and UvrD helicases. Finally, Rep
      and UvrD also act at inverted sequences other than rrn, and promote replication
      through highly transcribed regions in wild-type E. coli.

PMID- 19851283
TI  - Inhibition of the shade avoidance response by formation of non-DNA binding bHLH
      heterodimers.
AB  - In shade-intolerant plants such as Arabidopsis, a reduction in the red/far-red
      (R/FR) ratio, indicative of competition from other plants, triggers a suite of
      responses known as the shade avoidance syndrome (SAS). The phytochrome
      photoreceptors measure the R/FR ratio and control the SAS. The phytochrome
      interacting factors 4 and 5 (PIF4 and PIF5) are stabilized in the shade and are
      required for a full SAS, whereas the related bHLH factor HFR1 (long hypocotyl in
      FR light) is transcriptionally induced by shade and inhibits this response. Here
      we show that HFR1 interacts with PIF4 and PIF5 and limits their capacity to
      induce the expression of shade marker genes and to promote elongation growth.
      HFR1 directly inhibits these PIFs by forming non-DNA-binding heterodimers with
      PIF4 and PIF5. Our data indicate that PIF4 and PIF5 promote SAS by directly
      binding to G-boxes present in the promoter of shade marker genes, but their
      action is limited later in the shade when HFR1 accumulates and forms non-DNA
      binding heterodimers. This negative feedback loop is important to limit the
      response of plants to shade.

PMID- 19851284
TI  - Neural stem cell transcriptional networks highlight genes essential for nervous
      system development.
AB  - Neural stem cells must strike a balance between self-renewal and multipotency,
      and differentiation. Identification of the transcriptional networks regulating
      stem cell division is an essential step in understanding how this balance is
      achieved. We have shown that the homeodomain transcription factor, Prospero, acts
      to repress self-renewal and promote differentiation. Among its targets are three
      neural stem cell transcription factors, Asense, Deadpan and Snail, of which
      Asense and Deadpan are repressed by Prospero. Here, we identify the targets of
      these three factors throughout the genome. We find a large overlap in their
      target genes, and indeed with the targets of Prospero, with 245 genomic loci
      bound by all factors. Many of the genes have been implicated in vertebrate stem
      cell self-renewal, suggesting that this core set of genes is crucial in the
      switch between self-renewal and differentiation. We also show that multiply bound
      loci are enriched for genes previously linked to nervous system phenotypes,
      thereby providing a shortcut to identifying genes important for nervous system
      development.

PMID- 19851285
TI  - Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by
      ATM and/or DNA-PK.
AB  - Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at
      a DNA 3' end linked to a tyrosyl moiety. This type of linkage is found at stalled
      topoisomerase I (Top1)-DNA covalent complexes, and TDP1 has been implicated in
      the repair of such complexes. Here we show that Top1-associated DNA double
      stranded breaks (DSBs) induce the phosphorylation of TDP1 at S81. This
      phosphorylation is mediated by the protein kinases: ataxia-telangiectasia-mutated
      (ATM) and DNA-dependent protein kinase (DNA-PK). Phosphorylated TDP1 forms
      nuclear foci that co-localize with those of phosphorylated histone H2AX
      (gammaH2AX). Both Top1-induced replication- and transcription-mediated DNA
      damages induce TDP1 phosphorylation. Furthermore, we show that S81
      phosphorylation stabilizes TDP1, induces the formation of XRCC1 (X-ray cross
      complementing group 1)-TDP1 complexes and enhances the mobilization of TDP1 to
      DNA damage sites. Finally, we provide evidence that TDP1-S81 phosphorylation
      promotes cell survival and DNA repair in response to CPT-induced DSBs. Together;
      our findings provide a new mechanism for TDP1 post-translational regulation by
      ATM and DNA-PK.

PMID- 19851286
TI  - Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases
      Rad18 and Rad5.
AB  - Poly-ubiquitylation is a common post-translational modification that can impart
      various functions to a target protein. Several distinct mechanisms have been
      reported for the assembly of poly-ubiquitin chains, involving either stepwise
      transfer of ubiquitin monomers or attachment of a preformed poly-ubiquitin chain
      and requiring either a single pair of ubiquitin-conjugating enzyme (E2) and
      ubiquitin ligase (E3), or alternatively combinations of different E2s and E3s. We
      have analysed the mechanism of poly-ubiquitylation of the replication clamp PCNA
      by two cooperating E2-E3 pairs, Rad6-Rad18 and Ubc13-Mms2-Rad5. We find that the
      two complexes act sequentially and independently in chain initiation and stepwise
      elongation, respectively. While loading of PCNA onto DNA is essential for
      recognition by Rad6-Rad18, chain extension by Ubc13-Mms2-Rad5 is only slightly
      enhanced by loading. Moreover, in contrast to initiation, chain extension is
      tolerant to variations in the attachment site of the proximal ubiquitin moiety.
      Our results provide information about a unique conjugation mechanism that appears
      to be specialised for a regulatable pattern of dual modification.

PMID- 19851289
TI  - Morning blood pressure surge: ready for daily clinical practice?

PMID- 19851290
TI  - Alcohol consumption and morning rise in blood pressure in men from a population
      based study.

PMID- 19851287
TI  - Self-regulation of Stat3 activity coordinates cell-cycle progression and neural
      crest specification.
AB  - A complex set of extracellular signals is required for neural crest (NC)
      specification. However, how these signals function to coordinate cell-cycle
      progression and differentiation remains poorly understood. Here, we report in
      Xenopus a role for the transcription factor signal transducers and activators of
      transcription-3 (Stat3) in this process downstream of FGF signalling. Depletion
      of Stat3 inhibits NC gene expression and cell proliferation, whereas
      overexpression expands the NC domain and promotes cell proliferation. Stat3 is
      phosphorylated and activated in ectodermal cells by FGFs through binding with
      FGFR4. Stat3 activation is also modulated by Hairy2 and Id3 proteins that,
      respectively, facilitate and disrupt Stat3-FGFR4 complex formation. Furthermore,
      distinct levels of Stat3 activity control Hairy2 and Id3 transcription, leading
      to Stat3 self-regulation. Finally, high Stat3 activity maintains cells in an
      undifferentiated state, whereas low activity promotes cell proliferation and NC
      differentiation. Together, our data suggest that Stat3, downstream of FGFs and
      under the positive and negative feedback regulation of Hairy2 and Id3, plays an
      essential role in the coordination of cell-cycle progression and differentiation
      during NC specification.

PMID- 19851291
TI  - Blood pressure, aging, vascular disease, and their effects on brain volume.

PMID- 19851292
TI  - Relationship between alcohol consumption and total mortality in hypertensive
      women.

PMID- 19851294
TI  - Decrease in FASN expression in adipose tissue of hypertensive individuals.
AB  - BACKGROUND: Fatty acid (FA) synthesis enzymes (FA synthase (FASN) and acetyl-CoA
      carboxylase (ACC)) are related to metabolic alterations such as obesity, insulin
      resistance, or dyslipidemia. Due to the fact that there is no literature that
      relates FASN and ACC expression with hypertension, we investigate how FASN and
      ACC expression in adipose tissue is related to hypertension. METHODS: This study
      included 87 patients, undergoing laparoscopic surgery procedures after an
      overnight fast. These patients were classified according to hypertension levels
      into two groups, normotensive and hypertensive, with a wide range of body mass
      index (BMI) in order to measure gene expression levels of FASN and ACC and
      anthropometric and biochemical variables. RESULTS: The main result of this work
      is a significant decrease of FASN expression in adipose tissue of hypertensive
      vs. normotensive patients, and that FASN may predict systolic blood pressure
      (SBP) values by multiple regression analysis and there was also an inverse
      correlation between FASN expression and SBP. CONCLUSIONS: In conclusion, to our
      knowledge it has been proven, for the first time, that there is a decrease of
      FASN expression in hypertensive individuals. The clinical significance of this
      work represents an exciting challenge because it would need to be clarified
      whether the reduced values of FASN expression may be associated with hypertension
      or whether this is an adaptive mechanism to the presence of hypertension. Once
      this aspect is clarified, it could be a new target for the treatment of
      hypertension.

PMID- 19851295
TI  - Association of hypertension treatment and control with all-cause and
      cardiovascular disease mortality among US adults with hypertension.
AB  - BACKGROUND: Clinical trials have provided convincing evidence that blood pressure
      (BP) lowering treatment reduces the risk of cardiovascular disease (CVD) and
      total mortality. The objective of this study was to examine the association of
      hypertension treatment, control, and BP indexes with all-cause and cardiovascular
      mortality among US adults with hypertension. METHODS: Persons aged > or =18 years
      from the Third National Health and Nutrition Examination Survey (NHANES III) were
      identified as hypertensives based on a BP > or =140/90 mm Hg or current treatment
      for hypertension. Vital status in 2006 was ascertained by passive follow-up using
      the National Death Index. Cox regression models were used to assess correlates of
      survival. RESULTS: At baseline, 52% of hypertensive adults reported currently
      taking prescription medicine for high BP and 38% of treated persons had BP
      controlled. Compared to treated controlled hypertensives, treated uncontrolled
      hypertensives had a 1.57-fold (95% confidence interval (CI) 1.28-1.91) and 1.74
      fold (95% CI 1.36-2.22) risk of all-cause and cardiovascular mortality; untreated
      hypertensives had a 1.34-fold (95% CI 1.12-1.62) and 1.37-fold (95% CI 1.04-1.81)
      risk of all-cause and cardiovascular mortality, respectively. The association
      persisted after further excluding persons with pre-existing hypertension
      comorbidities. Mortality risk was linearly increased with systolic BP (SBP),
      pulse pressure (PP), and mean arterial pressure (MBP), whereas diastolic BP (DBP)
      was not a significant predictor of cardiovascular mortality overall. No
      significant associations were observed between drug classes and mortality risk.
      CONCLUSIONS: This study indicates that uncontrolled and untreated hypertension
      was associated with increased risk of total and cardiovascular mortality among
      the general hypertensive population.

PMID- 19851296
TI  - Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals.
AB  - BACKGROUND: Hypertension is a major risk factor for cardiovascular disease.
      Although genetic studies have suggested that several genetic variants increase
      the risk for hypertension, the genes that underlie genetic susceptibility to this
      condition remain to be identified definitively. The purpose of the present study
      was to identify genetic variants that confer susceptibility to hypertension in
      Japanese individuals. METHODS: A total of 5,734 Japanese individuals from two
      independent populations were examined: subject panel A comprised 2,066
      hypertensive individuals and 824 controls; and subject panel B comprised 834
      hypertensive individuals and 2,010 controls. The 150 polymorphisms examined in
      the present study were selected by genome-wide association studies of myocardial
      infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K
      Array Set (Affymetrix). RESULTS: The chi(2)-test revealed that 10 polymorphisms
      were significantly (P < 0.05) related to the prevalence of hypertension in
      subject panel A. To validate the relations, these polymorphisms were examined in
      subject panel B. The A-->G polymorphism (rs645106) of SDK1 and the C-->G
      polymorphism (rs12078839) of RABGAP1L were significantly associated with
      hypertension in subject panel B. Multivariable logistic regression analysis with
      adjustment for covariates, as well as a stepwise forward selection procedure
      revealed that the A-->G polymorphism of SDK1 was significantly associated with
      hypertension in both subject panels A and B, with the G allele protecting against
      this condition. CONCLUSIONS: SDK1 may be a susceptibility gene for hypertension
      in Japanese individuals, although the functional relevance of the identified
      polymorphism was not determined.

PMID- 19851297
TI  - Left ventricular geometry in children and adolescents with primary hypertension.
AB  - BACKGROUND: Children with hypertension (HTN) are at increased risk for left
      ventricular hypertrophy (LVH). Increased left ventricular (LV) mass (LVM) by the
      process of remodeling in response to volume or pressure loading may be eccentric
      (increased LV diameter) or concentric (increased wall thickness). Our objective
      was to classify LV geometry among children with primary HTN and examine
      differences in ambulatory blood pressure (ABP). METHODS: Subjects aged 7-18 years
      with suspected HTN were enrolled in this cross-sectional study. ABP and LVM index
      (LVMI) were measured within the same 24-h period. LV geometry was classified as
      normal, concentric remodeling, concentric LVH, or eccentric LVH. RESULTS:
      Children with LVH had significantly higher ambulatory systolic BP (SBP) and
      diastolic blood pressure (BP) (DBP) levels and body mass index (BMI) Z-score.
      Sixty-eight children had HTN based upon ABP monitoring (ABPM). Thirty-eight
      percent of the hypertensive subjects had LVH, with equal distribution in the
      concentric and eccentric groups. There were significant differences in the 24-h
      DBP parameters when the eccentric LVH group was compared to the normal geometry
      and concentric LVH groups. Relative wall thickness (RWT) was inversely associated
      with night time DBP parameters. These relationships persisted after controlling
      for BMI Z-score. CONCLUSIONS: Although the risk for LVH is associated with
      increased SBP and BMI Z-score, those with eccentric LVH had significantly higher
      DBP.

PMID- 19851298
TI  - Oral L-citrulline supplementation attenuates blood pressure response to cold
      pressor test in young men.
AB  - BACKGROUND: Oral L-citrulline is efficiently converted to L-arginine, which has
      been shown to decrease brachial blood pressure (BP) at rest and during the cold
      pressor test (CPT). However, aortic BP may better reflect cardiovascular risk
      than brachial BP. The purpose of this study was to test the hypothesis that oral
      L-citrulline supplementation attenuates brachial BP and aortic hemodynamic
      responses to CPT. METHODS: Brachial BP, aortic BP, stroke volume (SV), and wave
      reflection at rest and during CPT were evaluated in 17 young (21.6 +/- 0.9 years)
      normotensive men. Subjects were randomly assigned to 4 weeks of oral L-citrulline
      (6 g/day) or placebo in a crossover design. Hemodynamic responses to CPT were
      reevaluated after each treatment. RESULTS: During CPT, there were significant (P
      < 0.05) increases in brachial and aortic BP [systolic (SBP), diastolic (DBP), and
      pulse pressure (PP)], augmentation index (AIx), SV, and a decrease in transit
      time of the reflected wave (Tr) from baseline. Compared to placebo, oral L
      citrulline treatment decreased (P < 0.05) brachial SBP (-6 +/- 11 mm Hg), aortic
      SBP (-4 +/- 10 mm Hg), and aortic PP (-3 +/- 6 mm Hg) during CPT but not at rest.
      There was an inverse correlation (r = -0.40, P < 0.05) between changes in aortic
      SBP and Tr during CPT after L-citrulline supplementation. CONCLUSIONS: We
      conclude that oral L-citrulline supplementation attenuates the brachial SBP,
      aortic SBP, and aortic PP responses to CPT in young normotensive men. Increased
      wave reflection time contributes to the reduction in aortic SBP response to CPT.

PMID- 19851299
TI  - Linkage and genome-wide association analysis of obesity-related phenotypes:
      association of weight with the MGAT1 gene.
AB  - As major risk-factors for diabetes and cardiovascular diseases, the genetic
      contribution to obesity-related traits has been of interest for decades.
      Recently, a limited number of common genetic variants, which have replicated in
      different populations, have been identified. One approach to increase the
      statistical power in genetic mapping studies is to focus on populations with
      increased levels of linkage disequilibrium (LD) and reduced genetic diversity. We
      have performed joint linkage and genome-wide association analyses for weight and
      BMI in 3,448 (linkage) and 3,925 (association) partly overlapping healthy
      individuals from five European populations. A total of four chromosomal regions
      (two for weight and two for BMI) showed suggestive linkage (lod >2.69) either in
      one of the populations or in the joint data. At the genome-wide level (nominal P
      < 1.6 x 10(-7), Bonferroni-adjusted P < 0.05) one single-nucleotide polymorphism
      (SNP) (rs12517906) (nominal P = 7.3 x 10(-8)) was associated with weight, whereas
      none with BMI. The SNP associated with weight is located close to MGAT1. The
      monoacylglycerol acyltransferase (MGAT) enzyme family is known to be involved in
      dietary fat absorption. There was no overlap between the linkage regions and the
      associated SNPs. Our results show that genetic effects influencing weight and BMI
      are shared across diverse European populations, even though some of these
      populations have experienced recent population bottlenecks and/or been affected
      by genetic drift. The analysis enabled us to identify a new candidate gene,
      MGAT1, associated with weight in women.

PMID- 19851300
TI  - Weight status continuity and change from adolescence to young adulthood:
      examining disease and health risk conditions.
AB  - This study examined weight status during adolescence and young adulthood, and
      young adult health condition diagnosis. Data are from 10,439 African-American,
      Hispanic, and white men and women participating in the National Longitudinal
      Study of Adolescent Health during Waves 1 (adolescence: ages 12-19) and 3 (young
      adulthood: ages 19-26). Categories were created differentiating individuals based
      on their weight status during adolescence and young adulthood: (i) obese during
      adolescence and young adulthood (i.e., continuously obese), (ii) obese during
      adolescence only, (iii) obese during young adulthood only, and (iv) never obese.
      Multilevel random intercept regression models were used to examine the impact of
      obesity category, sex, and race/ethnicity on young adult asthma, diabetes, high
      cholesterol, and high blood pressure. Continuous obesity increased the likelihood
      for young adult disease and health risk conditions compared to individuals who
      were never obese. Obesity isolated to adolescence (Wave 1) increased the
      likelihood for high cholesterol and high blood pressure, whereas obesity isolated
      to young adulthood (Wave 3) also increased the likelihood for diabetes--all
      increases were relative to nonobese weight status during both periods.
      Associations varied in direction and degree when sex and race/ethnicity were
      considered. Findings clarify some of the mixed understandings regarding the
      associations between age of onset and stability of obesity, and health outcomes
      with important public health implications. Although results indicate obesity
      isolated to a single developmental period does have health repercussions, obesity
      experienced continuously during adolescence and young adulthood greatly
      intensified risk across all health conditions.

PMID- 19851301
TI  - Fasting plasma glucose (FPG) and the risk of impaired glucose tolerance in obese
      children and adolescents.
AB  - A timely diagnosis of impaired glucose tolerance (IGT) is desirable in obesity.
      The oral glucose tolerance test (OGTT), the gold standard to diagnose this
      condition, may not be realistically performed in all patients due to discomfort,
      labor, and cost. The aim of this study was to assess whether one or more
      biochemical indexes measured in fasting conditions could be used to identify
      obese children at risk of IGT. A cohort of 563 white obese children and
      adolescents (M/F: 315/248; aged 4-17 years) was recruited and underwent
      anthropometric evaluation and OGTT. Anthropometric parameters, fasting plasma
      glucose (FPG), fasting serum insulin (FSI), and homeostasis model assessment of
      insulin resistance (HOMA(IR)) were tested in pursuit of a possible threshold to
      be used as a predictor of IGT. Thirty-seven children (6.9%) had IGT and one child
      (0.1%) had type 2 diabetes (T2D). FPG, FSI, and HOMA(IR) were all significantly
      higher in children with IGT than in children without IGT. Receiver-operating
      characteristic (ROC) curve analyses run for gender and puberty-adjusted FPG, FSI,
      and HOMA(IR) were all significant: area under the curve (95% confidence interval)
      equaled 0.68 (0.59-0.76), 0.66 (0.56-0.76), and 0.68 (0.59-0.78), respectively.
      The three parameters did not show significantly different sensitivity/specificity
      in the pooled population or in the gender/puberty subgroups. Thresholds varied
      among gender/puberty subgroups for FSI and HOMA(IR), but not for FPG, which
      showed a fixed threshold of 86 mg/dl. A gender/puberty independent cutoff of FPG
      may be considered a screening tool to narrow clinical indication to OGTT in obese
      white children and adolescents.

PMID- 19851302
TI  - Identifying metabolically healthy but obese individuals in sedentary
      postmenopausal women.
AB  - The purpose of this study was to compare different methods to identify
      metabolically healthy but obese (MHO) individuals in a cohort of obese
      postmenopausal women. We examined the anthropometric and metabolic
      characteristics of 113 obese (age: 57.3 +/- 4.8 years; BMI: 34.2 +/- 2.7
      kg/m(2)), sedentary postmenopausal women. The following methods were used to
      identify MHO subjects: the hyperinsulinemic-euglycemic clamp (MHO: upper quartile
      of glucose disposal rates); the Matsuda index (MHO: upper quartile of the Matsuda
      index); the homeostasis model assessment (HOMA) index (MHO: lower quartile of the
      HOMA index); having 0-1 cardiometabolic abnormalities (systolic/diastolic blood
      pressure > or =130/85 mm Hg, triglycerides (TG) > or =1.7 mmol/l, glucose > or
      =5.6 mmol/l, HOMA >5.13, high-sensitive C-reactive protein (hsCRP) >0.1 mg/l,
      high-density lipoprotein-cholesterol (HDL-C) <1.3 mmol/l); and meeting four out
      of five metabolic factors (HOMA < or =2.7, TG < or =1.7 mmol/l, HDL-C > or =1.3
      mmol/l, low-density lipoprotein-cholesterol < or =2.6 mmol/l, hsCRP < or =3.0
      mg/l). Thereafter, we measured insulin sensitivity, body composition (dual-energy
      X-ray absorptiometry), body fat distribution (computed tomography scan), energy
      expenditure, plasma lipids, inflammation markers, resting blood pressure, and
      cardiorespiratory fitness. We found significant differences in body composition
      (i.e., peripheral fat mass, central lean body mass (LBM)) and metabolic risk
      factors (i.e., HDL-C, hsCRP) between MHO and at risk individuals using the
      different methods to identify both groups. In addition, significant differences
      between MHO subjects using the different methods to identify MHO individuals were
      observed such as age, TG/HDL, hsCRP, and fasting insulin. However, independently
      of the methods used, we noted some recurrent characteristics that identify MHO
      subjects such as TG, apolipoprotein B, and ferritin. In conclusion, the present
      study shows variations in body composition and metabolic profile based on the
      methods studied to define the MHO phenotype. Therefore, an expert consensus may
      be needed to standardize the identification of MHO individuals.

PMID- 19851303
TI  - Regulatory SNP in the RBP4 gene modified the expression in adipocytes and
      associated with BMI.
AB  - Retinol-binding protein 4 (RBP4) is a recently identified adipokine that was
      involved in insulin resistance. RBP4 is predominantly expressed from the liver in
      normal metabolic state to transport retinoids throughout the body, but the exact
      physiological function and the regulatory mechanisms of adipocyte-derived RBP4
      have not been revealed. We conducted the genetic analysis about metabolic
      parameters in Japanese and Mongolian; the minor allele carriers of regulatory
      single-nucleotide polymorphism (SNP -803G>A) showed significantly higher BMI in
      Japanese men (P = 0.009) and women (P = 0.017), and in Mongolian women (P =
      0.009). Relative quantification of RBP4 transcripts in -803GA heterozygotes
      showed that the minor allele-linked haplotype-derived mRNA was significantly more
      abundant than the transcript from major allele. RBP4 promoter assay in 3T3L1
      adipocytes revealed that the minor allele increased the promoter activity double
      to triple and the administration of 9-cis-retinoic acid (RA) and 8-bromo-cyclic
      adenosine monophosphate (8-Br-cAMP) enhanced the activity. Multiple alignment
      analysis of human, mouse, rat, and cattle RBP4 promoter suggested conserved seven
      transcription factor binding motifs. Electrophoretic mobility shift assay showed
      the -803G>A SNP modulate the affinity against unidentified DNA-binding factor,
      which was assumed to be a suppressive factor. These results collectively
      suggested that the minor allele of RBP4 regulatory SNP enhanced the expression in
      adipocytes, which may be associated with the adipogenesis.

PMID- 19851304
TI  - Traditional anthropometric parameters still predict metabolic disorders in women
      with severe obesity.
AB  - It is well established that fat distribution rather than the total quantity of
      fat is the major determinant of cardiovascular risk in overweight subjects.
      However, it is not known whether the concept of fat distribution still makes
      sense in severely obese subjects. Particularly, the role of visceral fat
      accumulation and/or of adipocyte hypertrophy in insulin resistance (IR) has not
      been studied in this population. Therefore, the aim of this study was to clarify
      the determinants of metabolic disorders in severely obese women. We performed a
      cross-sectional study in 237 severely obese women (BMI >35 kg/m(2)). We assessed
      total body fat mass and fat distribution by anthropometric measurements (BMI and
      waist-to-hip ratio (WHR)) and by dual-energy X-ray absorptiometry (DXA). In 22
      women, we measured subcutaneous and visceral adipocyte size on surgical biopsies.
      Mean BMI was 44 +/- 7 kg/m(2) (range 35-77), mean age 37 +/- 11 years (range 18
      61). Lipid parameters (triglycerides, high-density lipoprotein cholesterol) and
      IR markers (fasting insulin and homeostasis model assessment (HOMA) index)
      correlated with fat distribution, whereas inflammatory parameters (C-reactive
      protein, fibrinogen) correlated only with total fat mass. An association was
      observed between android fat distribution and adipocyte hypertrophy. Visceral
      adipocyte hypertrophy was associated with both IR and hypertension, whereas
      subcutaneous fat-cell size was linked only to hypertension. Our results obtained
      in a large cohort of women showed that fat distribution still predicts metabolic
      abnormalities in severe obesity. Furthermore, we found a cluster of associations
      among fat distribution, metabolic syndrome (MS), and adipocyte hypertrophy.

PMID- 19851305
TI  - The desire to eat in the presence of obese or normal-weight eaters as a function
      of their emotional facial expression.
AB  - The aim of this study was to investigate whether the eating desire would be lower
      in the presence of facial expression of an obese than of a normal-weight eater in
      participants who were or not themselves obese. Normal-weight and obese
      participants assessed their desire to eat liked and disliked foods. These foods
      were presented alone and with a normal-weight and obese eater expressing
      pleasure, disgust, or neutrality. Results showed that, compared with a normal
      weight eater, perceiving an obese eater decreased the viewer's desire to eat,
      whatever his/her facial expression. Thus, pleasant faces of normal weight but not
      of obese eaters increased the eating desire. Furthermore, the influence of
      eater's facial expressions did not differ as a function of the participants'
      BMIs. These data were discussed in the framework of the embodiment theory of
      emotion and of their implications in terms of nutritional education, either by
      enabling people to learn to like certain unpalatable foods or by helping them
      moderate their food intake simply through the sight of an obese eater.

PMID- 19851306
TI  - Hypolipidemic effect of fenugreek seeds is mediated through inhibition of fat
      accumulation and upregulation of LDL receptor.
AB  - Fenugreek (Trigonella foenum-graecum) seeds, used as a condiment, are documented
      for health benefits including amelioration of abnormalities in lipid homeostasis
      due to its hypolipidemic properties. However, molecular mechanisms underlying the
      hypolipidemic effect of fenugreek seeds remain obscure. In this study,
      hypolipidemic effect of a novel thermostable extract of fenugreek seeds (TEFS)
      was evaluated in vitro by employing differentiating and differentiated 3T3-L1
      cells, and HepG2 cells cultured in normal or sterol-enriched conditions.
      Hypolipidemic effect was studied by quantifying decrease in accumulation of fat
      or by western blot analysis of adipogenic and lipogenic factors. At molecular
      level, TEFS inhibited accumulation of fat in differentiating and differentiated
      3T3-L1 cells via decreased expression of adipogenic factors such as peroxisome
      proliferators activated-receptor-gamma (PPAR-gamma), sterol regulatory element
      binding protein-1 (SREBP-1), and CAAT element-binding proteins-alpha (c/EBP
      alpha). We also show that following TEFS treatment, cellular triglycerides (TGs),
      and cholesterol concentrations decreased significantly (P < 0.05) in HepG2 cells
      via reduced expression of SREBP-1, at mRNA as well as protein level. Under sterol
      enriched condition, TEFS upregulated low-density lipoprotein receptor (LDLR)
      expression resulting in enhanced LDL uptake. Treating fat supplement fed C57BL6/J
      mice with TEFS for 15 days resulted in decrease of serum TG, LDL-cholesterol
      (LDLc), and body weight in a dose- and time-dependent manner (P < 0.05). Results
      indicate that hypolipidemic effect of TEFS is due to inhibition of fat
      accumulation and upregulation of LDLR. Taken together, the study suggests that
      TEFS may have potential application in the management of dyslipidemia and its
      associated metabolic disorders.

PMID- 19851307
TI  - The imprinted gene neuronatin is regulated by metabolic status and associated
      with obesity.
AB  - Using restriction fragment differential display (RFDD) technology, we have
      identified the imprinted gene neuronatin (Nnat) as a hypothalamic target under
      the influence of leptin. Nnat mRNA expression is decreased in several key
      appetite regulatory hypothalamic nuclei in rodents with impaired leptin signaling
      and during fasting conditions. Furthermore, peripheral administration of leptin
      to ob/ob mice normalizes hypothalamic Nnat expression. Comparative
      immunohistochemical analysis of human and rat hypothalami demonstrates that NNAT
      protein is present in anatomically equivalent nuclei, suggesting human
      physiological relevance of the gene product(s). A putative role of Nnat in human
      energy homeostasis is further emphasized by a consistent association between
      single nucleotide polymorphisms (SNPs) in the human Nnat gene and severe
      childhood and adult obesity.

PMID- 19851308
TI  - Prenatal exposure to maternal cigarette smoking and accumulation of intra
      abdominal fat during adolescence.
AB  - In industrialized countries, prenatal exposure to maternal cigarette smoking
      (PEMCS) is the most common environmental insult to the fetus. Here, we tested the
      hypothesis that PEMCS amplifies accumulation of abdominal fat during the
      accelerated weight gain occurring in late puberty. This hypothesis was tested in
      508 adolescents (12-18 years, 237 exposed prenatally to maternal cigarette
      smoking) in whom subcutaneous and intra-abdominal fat were quantified with
      magnetic resonance imaging (MRI). We found that, in early puberty, exposed and
      nonexposed adolescents did not differ in MRI-based measures of adiposity. In late
      puberty, on the other hand, exposed compared with nonexposed adolescents
      demonstrated markedly higher quantities of both subcutaneous fat (by 26%, P =
      0.004) and intra-abdominal fat (by 33%, P = 0.001). These group differences
      remained virtually unchanged after adjusting for sex and potential confounders,
      including birth weight and breastfeeding. As such, our results suggest that PEMCS
      may represent a major risk factor for the development of abdominal obesity at the
      later stages of puberty.

PMID- 19851309
TI  - Genetic epidemiology of BMI and body mass change from adolescence to young
      adulthood.
AB  - The complex interplay between genes and environment affecting body mass gain over
      lifecycle periods of risk is not well understood. We use longitudinal sibling
      cohort data to examine the role of shared household environment, additive
      genetic, and shared genetic effects on BMI and BMI change. In the National
      Longitudinal Study of Adolescent Health, siblings and twin pairs sharing
      households for > or =10 years as adolescents (N = 5,524; mean = 16.5 +/- 1.7
      years) were followed into young adulthood (N = 4,368; mean = 22.4 +/- 1.8 years).
      Using a variance component approach, we quantified genetic and household effects
      on BMI in siblings and nonsiblings sharing household environments over time.
      Adjusting for race, age, sex, and age-by-sex interaction, we detected a
      heritability of 0.43 +/- 0.05 for BMI change. Significant household effects were
      noted during the young adulthood period only (0.11 +/- 0.06). We find evidence
      for shared genetic effects between BMI and BMI change during adolescence (genetic
      correlation (rho(G)) = 0.61 +/- 0.03) and young adulthood (rho(G) = 0.23 +/-
      0.06). Our findings support a complex etiology of BMI and BMI change.

PMID- 19851310
TI  - Hypothalamic paraventricular nucleus lesion involvement in the sympathetic
      control of lipid mobilization.
AB  - The sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) is
      the principal initiator of lipolysis. Using pseudorabies virus, a transneuronal
      viral tract tracer, brain sites involved in the SNS outflow to WAT have been
      identified previously by us. One of these sites, the hypothalamic paraventricular
      nucleus (PVH) that shows predominantly unilateral sympathetic outflow from each
      half of the nucleus to ipsilaterally located WAT depots, was tested for
      laterality in lipid accumulation/mobilization in Siberian hamsters. First we
      tested whether unilateral PVH electrolytic lesions (PVHx) would increase lipid
      accumulation in WAT pads ipsilateral to the side of the PVHx. PVHx significantly
      increased body and WAT pad masses compared with sham PVHx; however, there was no
      laterality effect. In addition, bilateral PVHx increased body and WAT pad masses,
      as well as food intake, to a greater extent than did unilateral PVHx. We next
      tested for possible laterality effects on WAT lipid mobilization using food
      deprivation as the lipolytic stimulus in hamsters bearing unilateral or bilateral
      PVHx. Lipid mobilization was not prevented, as indicated indirectly by WAT mass
      and thus laterality of lipid mobilization could not be tested. We then tested
      whether removal of adrenal catecholamines via adrenal demedullation (ADMEDx)
      alone, or combined with bilateral PVHx, would block food deprivation-induced
      lipid mobilization, but neither did so. These results suggest that an intact PVH
      is not necessary for food deprivation-induced lipid mobilization and support the
      primacy of the SNS innervation of WAT, rather than adrenal medullary
      catecholamines, for lipid mobilization from WAT.

PMID- 19851311
TI  - Validation of computed tomographic estimates of intra-abdominal and subcutaneous
      adipose tissue in rats and mice.
AB  - We characterized the accuracy, sensitivity, and reliability of computed
      tomographic (CT) estimates of intra-abdominal (IA) and subcutaneous (S) adipose
      tissue (AT) in rats and mice using the Aloka rodent CT. Here, we present the
      first comparisons of CT estimates of the weights of AT samples ex vivo to balance
      weights of the same samples, of CT estimates of AT weights in vivo to the weights
      of resected whole-body AT, and of CT estimates of the weights of pieces of AT
      inserted IA or S in vivo to the weights of the same pieces ex vivo. CT
      underestimated AT weight ex vivo by approximately 10%, and correction of the
      automated categorization of IAAT and SAT by Aloka software was required. After
      these adjustments, correlations (r) of CT estimates and balance weights of
      resected AT were > or =0.99 in rats and > or =0.92 in mice. CT was impressively
      sensitive: the 95% probability range of CT estimates of 10,000 mg AT inserts into
      rats was +/-780 mg and of 500 mg inserts into mice, +/-20 mg. Scans limited to
      the abdominal region correlated well (r > 0.90) with whole-body scan measures of
      IAAT and SAT in rats and with IAAT, but not SAT (r < 0.80), in mice. Sums of IAAT
      and SAT correlated well with body weight in rats (r > 0.90), but not in mice (r <
      0.80). Coefficients of variance (CVs) of duplicate scans were <5%. We conclude
      that CT is a valid tool for studies of AT weight in rats and mice, especially
      when rapid throughput or longitudinal measures are desired.

PMID- 19851312
TI  - Breast volume is an independent predictor of visceral and ectopic fat in
      premenopausal women.
AB  - It is suggested that a large breast size among women may predict type 2 diabetes
      risk independent of BMI and waist circumference (WC). The purpose of this study
      was to determine the independent associations of breast volume with
      cardiometabolic risk factors and regional fat distribution. A total of 92
      overweight or obese premenopausal women (age = 39.9 +/- 6.8 years) underwent full
      body magnetic resonance imaging (MRI) for the assessment of breast volume,
      visceral adipose tissue (VAT), abdominal and lower-body subcutaneous AT (SAT),
      and intermuscular AT (IMAT), a 2-h oral glucose tolerance test (OGTT), and
      fasting phlebotomy for assessment of triglyceride, total, high-density
      lipoprotein-, and low-density lipoprotein-cholesterol levels. Breast volume was
      not associated with any of the cardiometabolic risk factors assessed (P > 0.05).
      However, VAT was consistently associated with a number of cardiometabolic risk
      factors (OGTT glucose, OGTT insulin, and triglyceride levels) after controlling
      for age, BMI, WC, breast volume, and the other AT depots. In univariate models,
      breast volume was positively associated with VAT, IMAT, and abdominal and lower
      body SAT (P < 0.05). After controlling for age, BMI, and WC level, breast volume
      remained positively associated with VAT and IMAT (P < 0.05), such that women with
      the highest breast volume had approximately 1.1 and 1.3 kg more VAT and IMAT,
      respectively, but no more abdominal or lower-body SAT, by comparison to women
      with the smallest breast volume. Thus, the previously documented association
      between breast size and type 2 diabetes risk may be in part explained by excess
      VAT and/or IMAT deposition.

PMID- 19851313
TI  - Polycomb group proteins: navigators of lineage pathways led astray in cancer.
AB  - The Polycomb group (PcG) proteins are transcriptional repressors that regulate
      lineage choices during development and differentiation. Recent studies have
      advanced our understanding of how the PcG proteins regulate cell fate decisions
      and how their deregulation potentially contributes to cancer. In this Review we
      discuss the emerging roles of long non-coding RNAs (ncRNAs) and a subset of
      transcription factors, which we call cell fate transcription factors, in the
      regulation of PcG association with target genes. We also speculate about how
      their deregulation contributes to tumorigenesis.

PMID- 19851314
TI  - Emerging roles of E2Fs in cancer: an exit from cell cycle control.
AB  - Mutations of the retinoblastoma tumour suppressor gene (RB1) or components
      regulating the RB pathway have been identified in almost every human malignancy.
      The E2F transcription factors function in cell cycle control and are intimately
      regulated by RB. Studies of model organisms have revealed conserved functions for
      E2Fs during development, suggesting that the cancer-related proliferative roles
      of E2F family members represent a recent evolutionary adaptation. However, given
      that some human tumours have concurrent RB1 inactivation and E2F amplification
      and overexpression, we propose that there are alternative tumour-promoting
      activities for the E2F family, which are independent of cell cycle regulation.

PMID- 19851317
TI  - Uncertain next steps.

PMID- 19851315
TI  - STATs in cancer inflammation and immunity: a leading role for STAT3.
AB  - Commensurate with their roles in regulating cytokine-dependent inflammation and
      immunity, signal transducer and activator of transcription (STAT) proteins are
      central in determining whether immune responses in the tumour microenvironment
      promote or inhibit cancer. Persistently activated STAT3 and, to some extent,
      STAT5 increase tumour cell proliferation, survival and invasion while suppressing
      anti-tumour immunity. The persistent activation of STAT3 also mediates tumour
      promoting inflammation. STAT3 has this dual role in tumour inflammation and
      immunity by promoting pro-oncogenic inflammatory pathways, including nuclear
      factor-kappaB (NF-kappaB) and interleukin-6 (IL-6)-GP130-Janus kinase (JAK)
      pathways, and by opposing STAT1- and NF-kappaB-mediated T helper 1 anti-tumour
      immune responses. Consequently, STAT3 is a promising target to redirect
      inflammation for cancer therapy.

PMID- 19851316
TI  - NFAT proteins: emerging roles in cancer progression.
AB  - The roles of nuclear factor of activated T cells (NFAT) transcription factors
      have been extensively studied in the immune system. However, ubiquitous
      expression of NFAT isoforms in mammalian tissues has recently been observed, and
      a role for these transcription factors in human cancer is emerging. Various NFAT
      isoforms are functional in tumour cells and multiple compartments in the tumour
      microenvironment, including fibroblasts, endothelial cells and infiltrating
      immune cells. How do NFAT isoforms regulate the complex interplay between these
      compartments during carcinoma progression? The answers lie with the multiple
      functions attributed to NFATs, including cell growth, survival, invasion and
      angiogenesis. In addition to elucidating the complex role of NFATs in cancer, we
      face the challenge of targeting this pathway therapeutically.

PMID- 19851319
TI  - Oxide dielectrics: A change of direction.

PMID- 19851320
TI  - Magnetic shape memory: Magnetoelastic sponges.

PMID- 19851321
TI  - Biodegradable alloys: The glass window of opportunities.

PMID- 19851322
TI  - Organic electronics: Electrical contacts.

PMID- 19851323
TI  - Material witness: Shaking hands with robots.

PMID- 19851324
TI  - Abnormal nocturnal blood pressure profile is associated with mild cognitive
      impairment in the elderly: the J-SHIPP study.
AB  - Mild cognitive impairment (MCI), a syndrome characteristic of the transition
      phase between normal cognitive function and dementia, has been shown to carry the
      risk of progression to dementia. Dysregulation of blood pressure (BP) is thought
      to be an indicator of cerebrovascular damage, including cognitive impairment.
      Here, we investigated the possible association of circadian BP variation with MCI
      in community-dwelling persons exhibiting no definitive dementia. Our study
      enrolled 144 persons (68+/-7 years). Nocturnal BP profile was defined as dipper,
      with a 10-19% drop in nocturnal systolic BP; extreme dipper, >or=20% drop; non
      dipper, 0-10% drop; and riser, any increase in nocturnal BP. MCI was assessed
      using the MCI screen, a cross-validated, staff-administered battery of tests.
      Subjects with MCI (n=38) were significantly older (74+/-6, 67+/-6 years, P<0.001)
      and had higher frequency of apolipoprotein E varepsilon4 allele (36.8, 18.9%,
      P=0.018). Although the ambulatory measured BP and the percent changes in
      nocturnal systolic BP (-10+/-12% and -12+/-8%, respectively; P=0.291) did not
      differ between MCI subjects and normal controls, frequency of MCI was
      significantly higher in the extreme dippers (32.0%), non-dippers (30.0%) and
      risers (50.0%) than in dippers (13.2%, P=0.018). Multiple logistic regression
      analysis identified a blunted nocturnal BP decline, non-dipping or increase in
      nocturnal BP and extreme drop in BP as potent determinants of MCI (odds ratio
      3.062, P=0.039), after adjustment for possible confounding factors, including
      apolipoprotein E varepsilon4 genotype. Abnormal nocturnal BP profile was found to
      be a strong indicator of MCI in otherwise apparently healthy community-dwelling
      elderly persons.

PMID- 19851325
TI  - The ideal combination of anti-hypertensive drugs.

PMID- 19851326
TI  - Angiotensin antagonists could increase urine production and drinking in order to
      decrease renal problems in diabetes and hypertension.

PMID- 19851327
TI  - Central blood pressure, arterial stiffness and the heart in hypertensive
      patients.

PMID- 19851328
TI  - Preclinical cardiovascular abnormalities in patients in early stages of renal
      disease without nephrotic syndrome.

PMID- 19851329
TI  - Studies of the molecular mechanism of caspase-8 activation by solution NMR.
AB  - Caspases are the key players of apoptosis and inflammation. They are present in
      the cells as latent precursors, procaspases, and are activated upon an apoptotic
      or inflammatory stimulus. The activation mechanism of caspases has been studied
      extensively by biochemical and biophysical methods. Additional structural
      information on active caspases with a variety of different inhibitors bound at
      the active site is available. In this study, we investigated the cleavage
      mechanism of caspase-8 from its zymogen to active caspase-8 by solution NMR and
      by biochemical methods. The intermolecular cleavage reaction using the
      catalytically inactive C285A procaspase-8 mutant is triggered by adding caspase-8
      and followed by (15)N,(1)H-NMR spectroscopy. The spectrum that initially
      resembles the one of procaspase-8 gradually over time changes to that of caspase
      8, and disappearing peaks display exponential decaying intensities. Removal of
      either one of the cleavage recognition motifs in the linker, or phosphorylation
      at Tyr380, is shown to reduce the rate of the cleavage reaction. The data suggest
      that dimerization repositions the linker to become suitable for intermolecular
      processing by the associated protomer. Furthermore, analysis of inhibitor binding
      to the active caspase-8 reveals an induced-fit mechanism for substrate binding.

PMID- 19851331
TI  - Genetically modified abominations? Widespread opposition to GMOs might have deep
      seated cultural causes.

PMID- 19851330
TI  - IRF-1 transcriptionally upregulates PUMA, which mediates the mitochondrial
      apoptotic pathway in IRF-1-induced apoptosis in cancer cells.
AB  - Interferon regulatory factor-1 (IRF-1) is a transcription factor that acts as a
      tumor suppressor and causes apoptosis in cancer cells. We evaluated IRF-1-induced
      apoptosis in gastric cancer cell lines. We established stable clones in AGS cells
      that have a tetracycline-inducible IRF-1 expression system. We used these clones
      and recombinant adenovirus expressing IRF-1 to explore the mechanism of IRF-1
      induced apoptosis in gastric cancer. Expression of IRF-1 causes apoptosis in
      gastric cancer cell lines as shown by phosphatidylserine exposure and cleavage of
      caspase-8, caspase-3, and Bid with the mitochondrial release of cytochrome c.
      However, inhibition of caspase-8 and Bid did not inhibit apoptosis and did not
      decrease cleaved caspase-9 or mitochondrial release of cytochrome c. We then show
      that IRF-1 upregulates PUMA (p53 upregulated modulator of apoptosis), which is
      known to activate apoptosis by the intrinsic pathway; this can be p53
      independent. IRF-1 binds to distinct sites in the promoter of PUMA and activates
      PUMA transcription. Moreover, molecular markers of mitochondrial apoptosis are
      eliminated in PUMA knockout and knockdown cells and phosphatidylserine exposure
      is decreased dramatically. Finally, we show that IFN-gamma induces IRF-1-mediated
      upregulation of PUMA in cancer cells. We conclude that IRF-1 can induce apoptosis
      by the intrinsic pathway independent of the extrinsic pathway by upregulation of
      PUMA.

PMID- 19851332
TI  - Protein quality control--linking the unfolded protein response to disease.
      Conference on 'From Unfolded Proteins in the Endoplasmic Reticulum to Disease'.

PMID- 19851333
TI  - Structures of yeast glutathione-S-transferase Gtt2 reveal a new catalytic type of
      GST family.
AB  - Glutathione-S-transferases (GSTs) are ubiquitous detoxification enzymes that
      catalyse the conjugation of electrophilic substrates to glutathione. Here, we
      present the crystal structures of Gtt2, a GST of Saccharomyces cerevisiae, in apo
      and two ligand-bound forms, at 2.23 A, 2.20 A and 2.10 A, respectively. Although
      Gtt2 has the overall structure of a GST, the absence of the classic catalytic
      essential residues--tyrosine, serine and cysteine--distinguishes it from all
      other cytosolic GSTs of known structure. Site-directed mutagenesis in combination
      with activity assays showed that instead of the classic catalytic residues, a
      water molecule stabilized by Ser129 and His123 acts as the deprotonator of the
      glutathione sulphur atom. Furthermore, only glycine and alanine are allowed at
      the amino-terminus of helix-alpha1 because of stereo-hindrance. Taken together,
      these results show that yeast Gtt2 is a novel atypical type of cytosolic GST.

PMID- 19851334
TI  - Building ubiquitin chains: E2 enzymes at work.
AB  - The modification of proteins with ubiquitin chains can change their localization,
      activity and/or stability. Although ubiquitylation requires the concerted action
      of ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and
      ubiquitin ligases (E3s), it is the E2s that have recently emerged as key
      mediators of chain assembly. These enzymes are able to govern the switch from
      ubiquitin chain initiation to elongation, regulate the processivity of chain
      formation and establish the topology of assembled chains, thereby determining the
      consequences of ubiquitylation for the modified proteins.

PMID- 19851335
TI  - Traffic control: regulation of kinesin motors.
AB  - Kinesins are a family of molecular motors that use the energy of ATP hydrolysis
      to move along the surface of, or destabilize, microtubule filaments. Much
      progress has been made in understanding the mechanics and functions of the
      kinesin motors that play important parts in cell division, cell motility,
      intracellular trafficking and ciliary function. How kinesins are regulated in
      cells to ensure the temporal and spatial fidelity of their microtubule-based
      activities is less well understood. Recent work has revealed molecular mechanisms
      that control kinesin autoinhibition and subsequent activation, binding to cargos
      and microtubule tracks, and localization at specific sites of action.

PMID- 19851337
TI  - Evolution of biomolecular networks: lessons from metabolic and protein
      interactions.
AB  - Despite only becoming popular at the beginning of this decade, biomolecular
      networks are now frameworks that facilitate many discoveries in molecular
      biology. The nodes of these networks are usually proteins (specifically enzymes
      in metabolic networks), whereas the links (or edges) are their interactions with
      other molecules. These networks are made up of protein-protein interactions or
      enzyme-enzyme interactions through shared metabolites in the case of metabolic
      networks. Evolutionary analysis has revealed that changes in the nodes and links
      in protein-protein interaction and metabolic networks are subject to different
      selection pressures owing to distinct topological features. However, many
      evolutionary constraints can be uncovered only if temporal and spatial aspects
      are included in the network analysis.

PMID- 19851336
TI  - Non-muscle myosin II takes centre stage in cell adhesion and migration.
AB  - Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross
      linking and contractile properties and is regulated by the phosphorylation of its
      light and heavy chains. The three mammalian NM II isoforms have both overlapping
      and unique properties. Owing to its position downstream of convergent signalling
      pathways, NM II is central in the control of cell adhesion, cell migration and
      tissue architecture. Recent insight into the role of NM II in these processes has
      been gained from loss-of-function and mutant approaches, methods that
      quantitatively measure actin and adhesion dynamics and the discovery of NM II
      mutations that cause monogenic diseases.

PMID- 19851339
TI  - Meta-analysis of genetic association studies: methodologies, between-study
      heterogeneity and winner's curse.
AB  - Meta-analysis is a useful tool to increase the statistical power to detect gene
      disease associations by combining results from the original and subsequent
      replication studies. Recently, consortium-based meta-analyses of several genome
      wide association (GWA) data sets have discovered new susceptibility genes of
      common diseases. We reviewed the process and the methods of meta-analysis of
      genetic association studies. To conduct and report a transparent meta-analysis,
      the search strategy, the inclusion or exclusion criteria of studies and the
      statistical procedures should be fully described. Assessing consistency or
      heterogeneity of the associations across studies is an important aim of meta
      analysis. Random effects model (REM) meta-analysis can incorporate between-study
      heterogeneity. We illustrated properties of test for and measures of between
      study heterogeneity and the effect of between-study heterogeneity on conclusions
      of meta-analyses through simulations. Our simulation shows that the power of REM
      meta-analysis of GWA data sets (total case-control sample size: 5000-20,000) to
      detect a small genetic effect (odds ratio (OR)=1.4 under dominant model)
      decreases as between-study heterogeneity increases and then the mean of OR of the
      simulated meta-analyses passing the genome-wide significance threshold would be
      upwardly biased (winner's curse phenomenon). Addressing observed between-study
      heterogeneity may be challenging but give a new insight into the gene-disease
      association.

PMID- 19851338
TI  - Biased segregation of DNA and centrosomes: moving together or drifting apart?
AB  - Old and newly synthesized centrosomes have different microtubule nucleating
      abilities and they contribute to cell polarity when they migrate to opposite
      poles during cell division. The asymmetric localization of epigenetic marks and
      kinetochore proteins could lead to the differential recognition of sister
      chromatids and the biased segregation of DNA strands to daughter cells during
      cell division. We propose that this asymmetric localization is linked to biased
      chromatid segregation, which might also be related to the acquisition of distinct
      cell fates after mitosis.

PMID- 19851341
TI  - No association between a promoter NOS1 polymorphism (rs41279104) and Infantile
      Hypertrophic Pyloric Stenosis.
AB  - Infantile hypertrophic pyloric stenosis (IHPS) is a condition affecting infants
      in the first few months of life. The condition is manifested by persistent
      vomiting and is caused by a hypertrophied muscle obstructing the gastric outlet.
      The condition is treated by pyloromyotomy. The incidence is 1-8/1000 births and
      varies among different populations. The etiology of IHPS is unknown, but both
      genetic and environmental factors are thought to contribute to the disease.
      Genetic linkage analysis has so far localized five loci that could harbor genes
      contributing to IHPS. The only gene implicated in IHPS is the nitric oxide
      synthase gene (NOS1), in which a single nucleotide polymorphism (rs41279104) in
      the promoter region has been associated with the disease in 16 patients. In this
      study, we examined an association of this SNP in 54 familial and 28 sporadic
      cases with IHPS, and compared the results with normal controls using univariate
      and multiple logistic regression analysis. We could not confirm any association
      between the analyzed SNP and infantile hypertrophic pyloric stenosis.

PMID- 19851340
TI  - Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF,
      FAIM2 and MC4R in a Japanese population.
AB  - There is evidence that the obesity phenotype in the Caucasian populations is
      associated with variations in several genes, including neuronal growth regulator
      1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets
      variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL),
      brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2
      (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1
      (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann
      Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium
      channel tetramerisation domain containing 15 (KCTD15). To investigate the
      relationship between obesity and these genes in the Japanese population, we
      genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese
      subjects (n=1129, body mass index (BMI) > or =30 kg m(-2)) and normal-weight
      control subjects (n=1736, BMI <25 kg m(-2)). The SNP rs10913469 in SEC16B
      (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the
      TMEM18 gene (P=0.00015), all of which were in almost absolute linkage
      disequilibrium, were significantly associated with obesity in the Japanese
      population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated
      with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide
      association studies in the Caucasians also confer susceptibility to obesity in
      Japanese subjects.

PMID- 19851342
TI  - Uveitis-like syndrome and iris transillumination after the use of oral
      moxifloxacin.
AB  - OBJECTIVE: To report a newly recognized adverse effect of oral moxifloxacin.
      DESIGN: Observational case reports. PARTICIPANTS: Five patients who used oral
      moxifloxacin therapy. MAIN OUTCOME MEASURES: In five patients, a uveitis-like
      episode followed oral moxifloxacin therapy, afterwards they experienced
      photophobia. At slitlamp investigation, the patients showed almost complete iris
      transillumination, not restricted to one sector, and persistent mydriasis of the
      pupil, with no reaction to light and no near reflex. Follow-up of 3 years in one
      of the patients showed no change of symptoms. Only in one patient, with a history
      of anterior uveitis, an anterior chamber tap was positive for herpes simplex
      genome. Only after the use of moxifloxacin did she experience continuous
      photophobia. CONCLUSIONS: Iris transillumination and sphincter paralysis is a
      newly recognized adverse effect of oral moxifloxacin therapy.

PMID- 19851343
TI  - Immunohistochemical analysis of internal limiting membrane by confocal microscopy
      in a case of stage 4 idiopathic macular hole.

PMID- 19851344
TI  - The CVD paradox: mortality vs prevalence.

PMID- 19851345
TI  - Interventional cardiology: Renal artery stenting--which patients will benefit?

PMID- 19851346
TI  - Coronary artery disease: High field strength coronary MRA--ready for prime time?

PMID- 19851347
TI  - Arrhythmias: Unexplained sudden cardiac death--back to clinical evaluation.

PMID- 19851348
TI  - Pharmacotherapy: Cardiovascular effects of aldosterone blockade in CKD.

PMID- 19851350
TI  - National policies and strategies for noncommunicable diseases.
AB  - Good public policies are vital for protecting the health of populations. For the
      prevention and control of noncommunicable diseases (NCD), a single national
      policy is essential. Such a policy ensures clarity of vision and purpose, sets
      the platform for joint action to address risk factors and determinants that are
      shared by major NCDs, and provides coherence with other health and social
      policies. A national NCD policy also provides an overarching framework that
      enables governments to combine and balance synergistic public health strategies
      that target the whole population and those that target high-risk groups. Given
      that the adopted strategies are evidence-based and cost-effective, national NCD
      policy development can provide a strong basis for appropriate legislation and
      regulation in relation to tobacco control and promotion of healthy diet and
      physical activity. A national policy also serves as a vehicle to facilitate
      efficient and effective use of available public finances for NCD-related health
      care, while safeguarding equity. For the reasons alluded to above, a single
      national NCD policy is more appropriate than separate national polices for each
      individual NCD, particularly in low-income and middle-income countries that have
      a critical shortage of human and financial resources, including those necessary
      for policy development and implementation.

PMID- 19851349
TI  - Applications of cardiac multidetector CT beyond coronary angiography.
AB  - Noninvasive imaging of the coronary arteries using multidetector CT (MDCT)
      represents one of the most promising diagnostic imaging advances in contemporary
      cardiology. This challenging application has driven a rapid and impressive
      advancement in CT technology over the past 10 years; leading to increased spatial
      and temporal resolution, decreased scan times and substantial reductions in
      radiation dose. Recent technological improvements have not only improved the
      status of CT coronary angiography but have also enabled new functional myocardial
      applications that are gaining a foothold in clinical practice as adjuncts or
      replacements for conventional coronary angiographic studies. Wide-detector CT
      designs along with prospective ECG-triggered protocols have opened the
      possibility of performing multiple complementary myocardial measurements during a
      coronary CT exam with acceptable radiation and contrast exposure. In this Review,
      we discuss recent technical developments in cardiac MDCT and outline newly
      enabled noncoronary cardiac applications including viability assessment,
      myocardial perfusion and molecular imaging.

PMID- 19851351
TI  - JBIR-54, a new 4-pyridinone derivative isolated from Penicillium daleae Zaleski
      fE50.

PMID- 19851353
TI  - The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK
      combined with overexpression of Cx43 in glioma cells.
AB  - The disseminated neoplastic foci of malignant gliomas are essentially responsible
      for the limited efficacy of current available therapeutic modalities. Bone marrow
      derived stem cells (BMSCs) have the ability to migrate into these tumors and even
      track infiltrating tumor cells, making them to be promising cellular vehicles for
      delivering therapeutic agents to glioma cells. The herpes simplex virus thymidine
      kinase (HSV-TK)/ganciclovir (GCV) suicide gene therapy with a potent bystander
      effect has been considered as one of the most promising therapeutic strategies
      for malignant gliomas. In this study, we evaluate the anti-glioma effect of
      suicide gene therapy using BMSCs expressing HSV-TK combined with overexpression
      of connexin 43 (Cx43), which can restore the gap junction of intercellular
      communication and may enhance the bystander effect of suicide gene therapy. To
      assess the potential of BMSCs to track glioma cells, a spheroid co-culture system
      in matrigel was used to show that some BMSCs migrated to C6 glioma cell
      microspheres. Transwell assay showed the tumor tropic property of BMSCs. In
      addition, BrdU-labeled BMSCs injected directly into the cerebral hemisphere
      opposite to the established C6 rat gliomas were capable of migrating into the
      xenograft gliomas. C6 cell growth was more intensively inhibited by HSV-TK/GCV
      treatment mediated by BMSCs, and could be further enhanced by combination with
      Cx43 transfection into glioma cells. The same result was observed in vivo by the
      growth of C6 gliomas and the survival analysis of rats bearing C6 glioma. In
      conclusion, Cx43 combined with HSV-TK/GCV gene therapy using BMSCs as vehicles
      was highly effective in a rat glioma model and therefore hold great potential as
      a novel approach for the gene therapy of human malignant gliomas.

PMID- 19851352
TI  - Intratumoral delivery of shRNA targeting cyclin D1 attenuates pancreatic cancer
      growth.
AB  - The aim of this study was to assess the biological consequences of cyclin D1
      silencing in pancreatic cancer cells. A replication-defective lentivirus based
      small hairpin RNA (shRNA) system targeting cyclin D1 caused a marked reduction in
      cyclin D1 protein levels in ASPC-1 and BxPC3 pancreatic cancer cell lines in
      conjunction with decreased cell growth and invasiveness in vitro. Moreover, a
      single intratumoral injection of the recombinant lentivirus targeting cyclin D1
      attenuated the growth of pre-existing tumors arising from two distinct cell
      lines. This attenuated growth correlated with decreased proliferation and
      angiogenesis, as well as attenuated vascular endothelial growth factor
      expression. It is concluded that lentivirus-delivered shRNA targeting cyclin D1
      suppresses the growth, invasiveness, tumorigenicity and pro-angiogenic potential
      of human pancreatic cancer cells, thereby raising the possibility that
      intratumoral injections of viruses targeting cyclin D1 could provide a new
      therapeutic approach in pancreatic ductal adenocarcinoma.

PMID- 19851354
TI  - An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA
      vaccine.
AB  - The cytomegalovirus (CMV) promoter is considered to be one of the strongest
      promoters for driving the in vivo expression of genes encoded by DNA vaccines.
      However, the efficacy of DNA vaccines has so far been disappointing (particularly
      in humans), and this might be explained in part by histone deacetylase (HDAC)
      mediated chromatin condensation. Hence, we sought to investigate whether
      increasing the expression of DNA vaccine antigens with the HDAC inhibitor OSU
      HDAC42 would enhance the efficacy of DNA vaccines in vivo. A luciferase assay was
      used to determine the effects of OSU-HDAC42 on CMV promoter-driven DNA plasmids
      in vitro and in vivo. Three HDAC inhibitors were able to activate expression from
      the CMV promoter in NIH3T3 cells and MBT-2 bladder cancer cells. The expression
      of luciferase was significantly enhanced by co-administration of pCMV-luciferase
      and OSU-HDAC42 in mice. To explore whether OSU-HDAC42 could enhance the specific
      antitumor activity of a neu DNA vaccine driven by the CMV promoter, we evaluated
      therapeutic effects and immune responses in a mouse tumor natively overexpressing
      HER2/neu. Mice receiving OSU-HDAC42 in combination with the CMV-promoter neu DNA
      vaccine exhibited stronger antitumor effects than mice given the DNA vaccine
      only. In addition, a correlation between the antitumor effects and the specific
      cellular immune responses was observed in the mice receiving the DNA vaccine and
      OSU-HDAC42.

PMID- 19851355
TI  - Seriously moving on.

PMID- 19851356
TI  - Dental care artists.

PMID- 19851357
TI  - Protocol required.

PMID- 19851358
TI  - Negative terminology.

PMID- 19851360
TI  - Stray teeth.

PMID- 19851361
TI  - Time to retire.

PMID- 19851362
TI  - Ratio taste.

PMID- 19851363
TI  - Guarantees for dental work.

PMID- 19851365
TI  - Healthcare focus for UK citizens.

PMID- 19851367
TI  - Scottish GDPs oppose continuous registration.

PMID- 19851369
TI  - First for special care dentistry.

PMID- 19851376
TI  - Dental therapy in the United Kingdom: part 1. Developments in therapists'
      training and role.
AB  - The number of students entering training for dental therapy has been increasing
      rapidly over the last few years. In practice, the scope of their work has
      increased, both in terms of permitted duties and their range of clinical
      settings. The possibilities for dental practitioners to work with therapists is
      therefore increasing, so it is important for them to be clear about therapists'
      potential capacity to provide added value to the dental team. This paper, which
      is the first of four covering aspects of dental therapy in the UK, traces the
      history of dental therapy together with the development of therapists' training
      opportunities and emerging competencies, up to the present. The subsequent three
      papers will describe aspects of a survey of dental therapists undertaken in late
      2006.

PMID- 19851377
TI  - Hypopharyngeal foreign body masquerading as malignancy.
AB  - Foreign body ingestion in dental and ENT practice is a commonly encountered
      emergency. In most cases, particularly in adults, there is a definite history of
      its ingestion, the nature of the foreign body is usually identifiable and the
      patient almost always presents immediately. We report an unusual case of an
      elderly patient with a six month history of progressive dysphagia referred to us
      by the physicians after investigations which were highly suggestive of a
      hypopharyngeal malignancy. Surprisingly when a biopsy was attempted, the
      hypopharyngeal mass turned out to be a dental plate. Dentists and
      otolaryngologists should be aware that pharyngeal foreign bodies can present
      without a positive history and can have a clinical presentation mimicking
      malignancy. A history of head injury, dementia, alcohol and drug abuse should be
      specifically excluded. A routine examination of a patient with dysphagia should
      include eliciting a specific history of wearing dentures and examination of
      teeth. In future designs for dental plates, bridges and crowns the use of a radio
      opaque material should be considered.

PMID- 19851384
TI  - Perceptions of a simulated general dental practice facility - reported
      experiences from past students at the Maurice Wohl General Dental Practice Centre
      2001-2008.
AB  - This article assesses the perceived value of a simulated general dental practice
      centre as reported by past undergraduates over five years. Various aspects of
      teaching and related outcomes are explored based on responses received from
      anonymous questionnaires. A team based approach to cooperative learning led by
      current practitioners experienced in primary dental care was seen as pivotal to
      the huge success of the teaching model. Moreover the role of cooperative learning
      and its influence on building individual clinical confidence and acumen was
      considered highly beneficial as part of the transition from novice to expert.
      METHODOLOGY: An anonymous questionnaire was distributed to students six months
      after qualification for a period of five years. The last registered postal
      address held by the Institute was used for this purpose. The years surveyed were:
      2001-2002, 2002-2003, 2003-2004, 2005-2006 and 2007-2008. The questionnaire
      provided for both qualitative aspects of feedback and a quantitative
      representation of the overall perception of effectiveness of the General Dental
      Practice Centre, as expressed by a visual analogue scale. RESULTS: In total 135
      questionnaires were returned representing a return rate of 53%. From the
      responses received 99% of the students reported that they enjoyed their sessions
      at the Centre with 96% expressing satisfaction with the teaching regime. The mean
      visual analogue scale rating the centre overall was reported as 83%, with a year
      on year increase ranging from 76-92%. Rich qualitative data were derived from
      free text responses. CONCLUSION: A simulated general dental practice centre was
      highly rated by past dental students in terms of the overall learning experience
      received and its relevance to later vocational training. By far the most
      consistently reported attribute was the opportunity to practise close support
      four handed dentistry with a nurse. Training in practice management and
      organisational skills were viewed as important with effective teamwork and a
      friendly environment seen as conducive to building up knowledge and confidence.
      The role of experienced current primary care practitioners as teachers was seen
      to be very effective in this setting.

PMID- 19851385
TI  - Experience of workplace bullying behaviours in postgraduate hospital dentists:
      questionnaire survey.
AB  - OBJECTIVES: To determine the prevalence of bullying and experience of bullying
      behaviours among postgraduate hospital dentists. DESIGN: Questionnaire survey.
      SETTING: The study was conducted among a sample of dentally qualified trainees
      within the UK's Hospital Dental Service. SUBJECTS AND METHODS: Two hundred and
      twenty-seven postgraduate hospital dentists were sent an anonymous questionnaire
      by the dental deans of participating deaneries. MAIN OUTCOME MEASURES: Prevalence
      of bullying and prevalence of experience of bullying behaviours; differences in
      experience of bullying and bullying behaviours by gender and ethnic group.
      RESULTS: One hundred and thirty-six hospital dentists returned the questionnaire,
      a response rate of 60%. Thirty-four (25%) identified themselves as victims of
      bullying, and 63 (47%) had witnessed their colleagues being bullied. Irrespective
      of whether or not they labelled themselves as victims of bullying, in the
      previous year 82 (60%) dentists had experienced one or more of the bullying
      behaviours included in the checklist. Overall, there was no statistically
      significant difference in experience of bullying behaviours by gender or ethnic
      group though non-white participants were significantly more likely than white
      participants to have experienced four of the bullying behaviours. CONCLUSIONS:
      Rates of bullying and experience of bullying behaviours among postgraduate
      hospital dentists were consistent with those reported in other NHS settings.

PMID- 19851412
TI  - All aboard with Impact India.
AB  - Impact India Foundation is a global initiative supported by UNDF, Unicef and WHO,
      to assist in the prevention of disablement around the world. London practice
      Barbican Dental Care teamed up with the Foundation to provide essential
      equipment, and dentist Neil Sikka joined the team on board the Lifeline Express
      hospital train to provide free treatment to those in need in remote parts of
      India. This article is an account of his travels.

PMID- 19851413
TI  - If alcohol was a new drug.

PMID- 19851414
TI  - Phenytoin toxicity and thyroid dysfunction.
AB  - A 48-year-old woman with known epilepsy presented to the Emergency Department
      with a 1-day history of decreasing coordination, impaired speech, and recurrent
      falls. Phenytoin levels were measured and found to be grossly elevated at 170
      mmol/L. A diagnosis of phenytoin toxicity was made and she was treated by
      withdrawing the medication. During admission she was found to be profoundly
      hypothyroid despite being on adequate thyroid replacement therapy. Normalisation
      of phenytoin levels was associated with return of euthyroidism. The interaction
      between phenytoin, thyroid function, and thyroid replacement therapy is
      discussed.

PMID- 19851415
TI  - For public health doctors, alcohol is the new tobacco.

PMID- 19851416
TI  - Alcohol-related harm to others: a survey of physical and sexual assault in New
      Zealand.
AB  - AIM: To describe the 12-month prevalence of physical and sexual assault, and the
      association of assault with drinking by the perpetrator. METHODS: Population
      based survey of 16,480 adult New Zealanders, using computer assisted telephone
      interviewing (CATI). RESULTS: Nearly 7% of men and 3% of women reported having
      been physically assaulted in the previous year, with 44% of these people having
      suffered more than one assault. One percent of women and 0.4% of men reported
      sexual assault, with 45% assaulted more than once. More than half of all physical
      assaults and sexual assaults involved a perpetrator who was reported to have been
      drinking. Perpetrators who had been drinking at the time were more likely to be
      strangers or other people outside the respondent's family, rather than relatives,
      and the assaults were less likely to have occurred inside the respondent's home,
      compared with assaults where the perpetrator was not drinking. Physical and
      sexual assaults were also associated with usual drinking patterns of the victims.
      CONCLUSION: Alcohol use by someone other than the victim is involved in more than
      half of reported assaults. Our findings suggest that, in New Zealand, more than
      62,000 physical assaults and 10,000 sexual assaults occur every year which
      involve a perpetrator who has been drinking. Of these, 10,500 incidents require
      medical attention and 17,000 involve police. This burden can be reduced using
      population-based strategies of demonstrated effectiveness.

PMID- 19851417
TI  - Alcohol and injury: a survey in primary care settings.
AB  - AIMS: Several high profile events in Dunedin have focused attention on alcohol
      related harm in the city. We sought to obtain local information regarding alcohol
      use and drinking location in order to better inform planning for local strategies
      to reduce alcohol-related harm in the future. METHODS: A cross-sectional survey
      of first-presentation injury consultations for patients 16 years and older
      presenting to three primary care facilities was undertaken over a 2-month period.
      The anonymous survey provided information about the nature of the injury, alcohol
      use in the 6 hours prior to injury, and identification of the location where the
      'last drink' was consumed. RESULTS: 17% of people aged 16 and over presenting to
      the three practices had had an alcoholic drink in the 6 hours prior to injury. Of
      this group, 36% had had moderate intake of alcohol and 64% a hazardous intake
      according to the ALAC criteria for the maximum number of standard drinks on one
      drinking occasion of 4 for women and 6 for men. The mean number of standard
      drinks recalled by drinkers in this survey was 9. Tertiary students and young
      people were more likely to have been drinking than others, and a greater
      proportion of women (24%) had been drinking prior to injury than men (11%).The
      majority of drinkers (62%) had their last drink at a house or flat. CONCLUSIONS:
      These results provide new information with respect to the role of drinking
      location in alcohol-related harm, in particular the important role of drinking in
      private homes. It also demonstrates the association between alcohol and injury in
      primary care settings in New Zealand. The current review of the Sale of Liquor
      Act is timely and should consider restricting the availability of alcohol in on
      and off licensed premises in order to minimise hazardous drinking in a range of
      drinking locations.

PMID- 19851418
TI  - In vivo interactions between BZP and TFMPP (party pill drugs).
AB  - AIM: This study explores potential drug-drug interactions between BZP and TFMPP.
      This was achieved by comparing the metabolism and pharmacokinetics of BZP and
      TFMPP when taken together with previously published data on their individual
      metabolism and pharmacokinetics. METHOD: Blood and urine samples were collected
      from seven participants given a combined dose of BZP (100 mg) and TFMPP (30 mg)
      and analysed by LC-MS in order to quantify the concentrations of BZP, TFMPP, and
      their major hydroxylated metabolites 3-OH BZP, 4-OH BZP, and 4-OH TFMPP. RESULTS:
      The metabolic profiles of both drugs were altered when co-administered. Both BZP
      and TFMPP lost one metabolite, 3-OH BZP and 4-OH TFMPP, respectively. Some
      differences in the pharmacokinetic properties of TFMPP were also noted.
      CONCLUSION: Metabolic interactions between BZP and TFMPP are clearly observed in
      this study along with some changes to the pharmacokinetics of TFMPP. As these
      drugs are often co-administered, the interactions between them are both relevant
      and concerning. Awareness of these interactions can assist clinicians in
      understanding toxicities relating to the co-administration of BZP and TFMPP or
      other party pill drugs.

PMID- 19851419
TI  - Unequal risks, unmet needs: the tobacco burden for Pacific peoples in New
      Zealand.
AB  - AIM: To review the available published literature and documentary material
      relevant to smoking by Pacific peoples in New Zealand. METHODS: Electronic
      databases and websites were searched using a range of search words. RESULTS: Over
      30% of Pacific adults in New Zealand reporting being smokers in the 2006 Census,
      compared to 21% of the whole adult population. Smoking by Pacific women increased
      from 23% in 1996 to 27% in the 2006 census. Other survey data indicates some fall
      in the prevalence of daily smoking from 35% in 2002/3 to 26% in 2006/7. The
      prevalence of smoking by Pacific Year-10 students declined sharply during 1999
      2007, from 29% to 16%. Smoking inside the homes of Pacific students has declined
      during 2001-7, from 35% to 26%. We found little government attention to smoking
      by Pacific peoples, and no specific central government plan for Pacific tobacco
      control. CONCLUSIONS: The threat to health from smoking and secondhand smoke
      exposure is higher for Pacific peoples and contributes to health inequalities in
      New Zealand. There is a need for tobacco control interventions specific to
      Pacific peoples, with some policy shortcomings needing to be urgently addressed.
      A central government plan for Pacific tobacco control is required. Some progress
      has occurred, particularly in the decrease of smoking by Pacific youth, and the
      increase in smokefree Pacific homes.

PMID- 19851420
TI  - Smokefree cars in New Zealand: rapid research among stakeholders on attitudes and
      future directions.
AB  - AIM: To conduct a rapid appraisal of the attitudes of New Zealand decision makers
      and tobacco control stakeholders on enacting a smokefree cars law. METHODS: A
      media and document search was made for relevant official and other statements. In
      early 2008, nine semi-structured interviews were carried out involving three MPs,
      two officials of government health agencies and four members of NGOs with a stake
      in tobacco control. Interviews were audiotaped, transcribed, and analysed for
      themes. RESULTS: In official statements, and amongst the interview sample, there
      was general opposition to giving smokefree car legislation a current high
      priority. Reasons given for opposition to such a law included the suboptimal use
      of advocacy capital compared with other initiatives (e.g. tobacco display bans),
      the perceived success of relevant health marketing campaigns, and concerns over
      the current political will to enact legislation that targets smoker freedoms.
      CONCLUSIONS: More information on the extent of current child exposure to tobacco
      smoke in New Zealand cars, and on the reach and effectiveness of the New Zealand
      smokefree cars media campaign would help advocates and policymakers. Wider
      dissemination to policymakers of New Zealand public and smoker support for
      banning smoking in cars, and of the progress overseas on smokefree car laws,
      appears to be essential.

PMID- 19851421
TI  - Smokefree outdoor areas without the smoke-police: the New Zealand local authority
      experience.
AB  - AIM: To investigate (i) the extent, nature and effectiveness of smokefree outdoor
      area (SFOA) policies in New Zealand, (ii) incentives and motivations for, and
      barriers to creating these SFOA. METHODS: Literature and media searches were
      conducted for relevant material to February 2009. Nine in-depth interviews were
      conducted in October 2008, with key informants from local government, health and
      related research areas. RESULTS: Twenty-three of 73 local authorities have
      'educative' (non-enforceable) SFOA policies for at least one playground. There
      has been an increasing trend of SFOA policy adoption since the first 'educative'
      policy in 2005. Motivations for policy adoption include child well-being,
      community leadership, and environmental and fire concerns. Barriers have included
      arguments about 'freedoms', over-regulation, park attendance, enforcement, media
      comment, and some local authority lack of focus on health. There appears to be
      increasing support nationally for at least SFOA for children's areas, including
      66% support from smokers for smokefree playgrounds. There is some evidence of
      SFOA policy effectiveness, but considerable need for further evaluation of the
      policies. CONCLUSIONS: Councils have moved to create SFOA, in the absence of
      substantial central government efforts. It is likely that the adoption of SFOA
      will continue, and there is potential for an expansion of the policies to wider
      settings.

PMID- 19851422
TI  - Support by New Zealand smokers for new types of smokefree areas: national survey
      data.
AB  - AIMS: To describe smoker support for new smokefree laws covering cars and outdoor
      settings, in a national sample of New Zealand (NZ) smokers. METHODS: The NZ arm
      of the International Tobacco Control Policy Evaluation Survey (ITC Project) uses
      as its sampling frame the NZ Health Survey (a nationally-representative sample
      interviewed face-to-face). From this sample we surveyed by telephone adult
      smokers (n=1376). Along with adjustment for the complex sample design, there was
      weighting of the results to attempt to adjust for the non-response at various
      points (i.e. there was an overall response rate of 33%). RESULTS: A majority of
      this national sample of smokers supported three new smokefree areas (albeit with
      some potential for response bias not adequately addressed by the weighting
      process). That is, only a minority agreed that smoking should be allowed: in cars
      with pre-school children (3%), anywhere in outdoor eating areas (22%), and at
      council-owned playgrounds (32%) (with a more equivocal minority for "within 5
      metres of the entrance to public buildings" (48%)). These attitudes were
      generally compatible with the findings that most of these smokers (87%) reported
      trying to minimise the amount that non-smokers were exposed to their cigarette
      smoke, and reported never smoking in a car with non-smokers (73%). Nevertheless,
      there were still domains where most smokers thought smoking should be allowed-
      e.g. on lifeguard-patrolled beaches (55%) and in at least some of the outdoor
      seating areas of restaurants/cafes (51%) and pubs (83%). CONCLUSIONS: There was
      majority support by these New Zealand smokers for three new types of smokefree
      areas not covered by current smokefree legislation (including in cars and some
      outdoor areas). These findings suggest it is a reasonable option for central
      government and local government authorities to further study and consider new
      smokefree laws.

PMID- 19851423
TI  - Survey of descriptors on cigarette packs: still misleading consumers?
AB  - AIM: In September 2008, the New Zealand (NZ) Commerce Commission issued a warning
      to the major tobacco companies to remove "light" and "mild" descriptors from
      cigarette packaging. Despite published evidence that suggested tobacco companies
      had started colour-coding their packs in anticipation of the Commission's
      decision, the investigation did not consider more general misleading packaging.
      This study explored changes in tobacco packaging that had been introduced to the
      New Zealand market, by surveying descriptors used on cigarette packs after the
      Commerce Commission's warning. METHOD: A convenience sample of discarded
      cigarette packs were collected in four cities and six towns/rural areas between
      November 2008 and January 2009. The majority of packs (93%) were collected in the
      capital city (Wellington). Information on the descriptors and pack colours was
      analysed. RESULTS: Four percent of the 1208 packs collected still included the
      terms "light" and "mild". Almost half the packs (42%) used a colour word (e.g.
      red, blue, gold) as a descriptor to indicate mildness or strength. A further 18%
      used other words that suggested mildness/strength (e.g. "subtle", "mellow"). A
      quarter of packs used a descriptor that did not connote either mildness or
      strength; however, the majority of these packs still appeared to be colour-coded.
      CONCLUSION: Although the words "light" and "mild" have been largely removed from
      tobacco packaging in the New Zealand market, these words have been replaced with
      associated colours or other words that may continue to communicate "reduced harm"
      messages to consumers. Further research to test how smokers interpret the new
      words and colours, and how these influence their behaviour, is desirable.
      However, government-mandated generic (plain) packaging would remove the
      opportunity to communicate misleading claims and so would afford the highest
      level of consumer protection.

PMID- 19851424
TI  - Alcohol cardio-protection has been talked up.
AB  - Doctors have been promoting alcohol as a health tonic for a very long time. The
      last 30 years has seen the accumulation of a considerable medical literature
      investigating the potential role of alcohol use as a protection against coronary
      heart disease. When viewed through the lens of two major early reviews in the mid
      1980s, Sir Richard Doll's contributions of the mid-1990s, two large meta-analyses
      of 10 years ago and two most recent overviews, the health-giving properties of
      alcohol use become increasingly debatable. The influence of the alcohol industry
      is raised as a factor in the exaggeration of alcohol use as a health
      intervention, in similar fashion to activities of pharmaceutical companies. The
      status of alcohol as a potentially dangerous recreational drug is emphasised as a
      warning against talking up alcohol as a cardio-protection manoeuvre by anyone.

PMID- 19851426
TI  - New Zealand Government response to climate change: largely fogged up?

PMID- 19851425
TI  - Medical image. Intracardiac slug.

PMID- 19851427
TI  - What is degeneration? The misuse of an ambiguous word.

PMID- 19851428
TI  - Signaling activated by the death receptors of the TNFR family.
AB  - BACKGROUND: The fine balance in cellular life and death is affected by a number
      of tightly regulated, direct signals that can help to turn the balance either in
      favor of or against the ultimate fate. Among the most prominent players in the
      field of the extracellular signals leading to cell death, preferentially through
      induction of apoptosis belong several receptors from so-called Death Receptors
      group of the Tumour Necrosis Factors Receptors (TNFR) family. METHODS AND
      RESULTS: Over 15 years of the research on activation and regulation of the most
      prominent member of this group - receptors for the ligands TRAIL, FasL and
      TNFalpha brought not only a detail (and still refining) mechanism of these
      receptors activation and downstream signaling, but also connected them with the
      ultimate apoptotic gatekeeper - mitochondria. Mitochondria are, in addition to
      their essential role as the energy factories also repositories of a cavalry of
      apoptosis-inducing as well as regulatory proteins. However, in addition to the
      pro-death signaling, these receptors were also shown under certain circumstances
      to activate an opposite, pro-proliferative signaling as well as to participate in
      pro-inflammatory responses. CONCLUSIONS: Thus despite the concerned effort of a
      number of groups and thousands of published papers, novel roles for the
      intriguing group of these receptors and their ligands and fine tuning of their
      signaling still await to be uncovered. This cut-through review will be mainly
      focused on the prominent death-inducing members of this group - TNFR1, Fas/CD95
      and TRAIL receptors.

PMID- 19851429
TI  - The role of magnetic resonance imaging for acute ischemic stroke.
AB  - BACKGROUND: Although computed tomography (CT) is still considered to be the gold
      standard of brain imaging before thrombolysis, new reperfusion strategies in
      acute ischemic stroke lead to more extensive use of magnetic resonance imaging
      (MRI). METHODS AND RESULTS: Diffusion- (DWI) and perfusion-weighted (PWI) MRI
      with MRI angiography are considered the most important examinations in diagnosis
      of acute ischemic stroke before reperfusion therapy. The effort to extend strict
      therapeutic time window resulted in the PWI/DWI mismatch concept, established to
      identify the presence of ischemic penumbra. Nevertheless, a lack of standards for
      methodology and analysis and existence of different alternative interpretations
      of such mismatch still present significant limitations of its use in routine
      clinical practice. CONCLUSION: MRI allows accurate diagnosis of the infarct
      lesion, detection of cerebral arterial occlusion or significant stenosis with
      evaluation of actual collateral flow and may also display certain reversible
      ischemic changes. However, the main objective for MRI still remains: improvement
      of non-invasive rapid and accurate identification of brain tissue at risk for
      infarction, which may be salvaged by safe and effective reperfusion therapy.

PMID- 19851430
TI  - Hypoxia sensing in cryptococcus neoformans: biofilm-like adaptation for dormancy?
AB  - BACKGROUND: Cryptococcus neoformans is an obligate aerobic pathogenic yeast
      causing lung infection typically followed by spread to the central nervous
      system. During pathogenesis, it relies on well-established virulence factors.
      This review focuses on the emerging role of cryptococcal adaptation to hypoxia in
      pathogenesis. METHODS AND RESULTS: We examined the MedLine database for
      information on the cryptococcal hypoxia response. While several recent papers
      describe components of two presumable hypoxia-sensing pathways including
      description of their target genes, a link of this system to the hypoxic tuning of
      proliferation is still missing. In addition, an interpretation of this knowledge
      in respect to the general picture of microbial pathogenesis is lacking.
      CONCLUSIONS: There seems to be a striking parallel between biofilm formation in
      bacteria, which results in chronic dormant infection with the potential for acute
      outbreaks, and the dormant state of primary infection followed by secondary
      outbreaks in C. neoformans. We propose a hypothesis that cryptococcal response to
      hypoxia might be the driving force for developing a state of dormant infection
      which is characterized by slowed proliferation and extensive changes in
      transcriptome and phenotype. This state enables C. neoformans to survive in host
      and possibly develop life-threatening acute outbreaks later. Hence, conventional
      well-aerated planktonic culture is not a good in vitro model for studying the
      pathogenesis of infection and we advocate the development of a more adequate
      model. Our further conclusion is that the ability of the immune system and
      antifungal agents to cope with hypoxia-adapted cells is crucial for the
      successful eradication of cryptococcal infection.

PMID- 19851431
TI  - Age-dependent decline in erythrocyte acetylcholinesterase activity: correlation
      with oxidative stress.
AB  - BACKGROUND: Oxidative stress hypothesis offers a mechanism for the aging process
      and its involvement in other pathologies such as diabetes and neurodegenerative
      diseases like Alzheimer. AChE activity in erythrocytes may be considered as a
      marker of central cholinergic status. The present study was undertaken to (i)
      determine the activity of erythrocyte AChE as a function of human process (ii)
      correlate AChE activity with oxidative stress during human aging. MATERIAL AND
      METHODS: Blood was collected from healthy subjects (n = 37) 22-82 years.
      Erythrocyte AChE activity, MDA and plasma antioxidant capacity in terms of FRAP
      was measured spectrophotometrically. RESULTS: There was a marked decrease in AChE
      activity with increasing age. The reduction in activity of AChE correlated well
      with increased lipid peroxidation and a decrease in FRAP values. CONCLUSION:
      Decreased antioxidant defense, and alteration in membrane rheology during aging
      process both may contribute towards decreased activity of AChE in erythrocyte
      membrane. This finding may help in explaining the neuronal complications taking
      place under conditions of oxidative stress, aging, and dementia.

PMID- 19851432
TI  - Use of formoterol in the treatment of stuttering. A pilot study.
AB  - AIMS: Stuttering is a serious health and social problem that can distinctively
      affect not only the mental development of an individual but also his life
      possibilities, including social fulfilment and his general life prospects. The
      etiology of stuttering is however unknown and that is why it is not possible to
      treat it causally. This pilot study takes into account the hypothesis of
      bronchial constriction as a negative factor in stuttering and investigates the
      effect of the long-acting bronchodilator formoterol fumarate on stuttering in 42
      patients. METHODS: Patients were divided in 2 groups - A (school children and
      juveniles) and B (adults 18-25 resistant to other treatment). The medicine was
      administered once a day in the morning in a dose of 12 microg for the total
      period of 6 months. The prime outcome parameter - severity of stuttering - was
      evaluated using the ordinary scale (McGill Pain Questionnaire). The evaluation
      was done by an examining physician during visits to the centres and by the
      patients themselves (in cases of the youngest with the assistance of a parent) in
      a daily diary. RESULTS: A non-parametric pair test (Wilcoxon signed rank test)
      was used to compare the average marks in the whole set of patients. During the
      six moth period of administration of Foradil the speech fluency improved. The
      average number of dysfluent words decreased from 10.5 +/- 1.3 to 6.6 +/-0.97.
      CONCLUSION: The average mark of speech fluency evaluated by the physicians
      between the period of non use of Foradil and the six month period after the use
      of Foradil improved from 2.95 +/- 0.76 to 1.95 +/- 0.56 (as proved by the chi
      square test, p<0.0001). The evaluation of speech fluency of balbuties uses the
      logopedic practices. Other clinical evaluations of speech fluency are not known.

PMID- 19851433
TI  - Impact of buccal glucose spray, liquid sugars and dextrose tablets on the
      evolution of plasma glucose concentration in healthy persons.
AB  - OBJECTIVES: The purpose of this prospective controlled trial was to assess the
      efficacy of three commercially available glucose products, (1) buccal glucose
      spray, (2) liquid sugars, and (3) dextrose tablet, on the evolution of plasma
      glucose concentration (PG). METHODS: Sixteen healthy volunteers aged 21.8 +/-
      0.78 y (mean +/- SE), BMI 23.5 +/- 0.84 kg/m(2), tested their PG over the course
      of 3 sets of 4 sessions (S) each: S(0)-control fasting, S(1)-buccal
      administration of 10 glucose spray-doses (0.84 g of glucose) without swallowing;
      S(2-) consumption of 1 sachet (13 ml) of liquid sugar (ca. 5.2 g glucose, 5.2 g
      fructose, 5.2 g sucrose); S(3-) consumption of one dextrose tablet (6 g). PG was
      tested in finger-prick capillary blood using a personal glucometer Linus at the
      start, and at 5, 10, 15, 20 and 30 min. The means of 3 respective sessions for
      each of the 16 subjects were analyzed. RESULTS: The Wilcoxon signed rank test
      revealed no significant differences between changes in the mean PG at the start
      vs. 5-minute interval either in control, or any intervention sessions. Analysis
      of regression coefficients after 30 min compared to the control session,
      demonstrated an increase in PG with the sachet of liquid sugars (0.068
      mmol/l/min, p = 0.001) which was greater than a single dextrose tablet (0.052
      mmol/l/min, p = 0.002), but no significant PG increase was found after buccal
      glucose spray. CONCLUSION: Liquid sugars or dextrose tablets, but not the buccal
      glucose spray, are effective means to increase PG within 10 minutes after
      ingestion.

PMID- 19851434
TI  - Rituximab does not adversely affect the stem cell mobilization and engraftment
      after high-dose therapy and autologous transplantation in patients with diffuse
      large B-cell lymphoma in first complete or partial remission.
AB  - AIMS AND METHODS: The goal was to investigate the effect of prior combined
      rituximab (R) and intensive chemotherapy on peripheral blood stem cell
      mobilization and their engraftment after stem cell transplantation (ASCT) in 69
      patients with poor-risk, diffuse large B-cell lymphoma (DLBCL). RESULTS: A
      statistically comparable median number of CD34+ stem cells was collected in both
      groups (13.80x10(6)/ kg in the non-R group and 7.81x10(6)/kg in the R group; p =
      0.110). A trend toward greater number of CFU-GM was found in the non-R group
      (98.1x10(4)/kg) compared to the R group (76.6x10(4)/kg; p = 0.068). The non-R
      patients had a much higher median number of BFU-E (90.9x10(4)/kg) than the R
      patients (31.3x10(4)/kg; p = 0.001). CONCLUSIONS: Hematopoietic engraftment was
      rapid for both groups and no different between them. The 3-year event-free
      survival was 90.4 % in the R group and 67.2 % in the non-R group (p = 0.04), but
      there was no significant difference in the 3-year overall survival (94,7 % vs
      83,5 %; p = 0.179).

PMID- 19851435
TI  - Comparison of the prevalence of genes coding for enterotoxins, exfoliatins,
      panton-valentine leukocidin and tsst-1 between methicillin-resistant and
      methicillin-susceptible isolates of Staphylococcus aureus at the university
      hospital in olomouc.
AB  - AIMS: Staphylococcus aureus is an important pathogen characterised by its
      potential to express many virulence factors. Currently, special attention is
      being paid to methicillin-resistant strains of S. aureus (MRSA). The aim of this
      study was to compare the prevalence of 13 selected virulence factor genes in
      methicillin-resistant versus methicillin-susceptible S. aureus (MSSA) isolates
      and to investigate their accumulation in the same isolate. METHODS: Real-time PCR
      was used to detect the presence of genes in 200 isolates of S. aureus (100 MRSA
      and 100 MSSA) from the University Hospital Olomouc collected in 2005-2006.
      RESULTS: Six out of the 13 monitored genes were detected more frequently in MRSA
      isolates: sea, seb, seg, sei, sej and eta, coding for the production of the
      enterotoxins A, B, G, I, J and the exfoliative toxin A. On the other hand, the
      pvl and tst genes coding for Panton-Valentine leukocidin and TSST-1 were more
      frequent in MSSA. Statistical analysis (chi-squared test) of the prevalence of
      virulence factors in the two groups showed a significant difference (P<0.05) in
      two cases (seg, sei). CONCLUSIONS: A higher prevalence of selected virulence
      genes was not confirmed in the methicillin-resistant S. aureus group. This
      indicates no further increase in their threat.

PMID- 19851436
TI  - Cerebral salt wasting syndrome in a patient with primary CNS lymphoma.
AB  - BACKGROUND: In patients with severe central nervous system (CNS) diseases, life
      threatening hyponatremia results from two main causes: the syndromes of
      inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting
      (CSW). Clinical manifestations of the two conditions may be similar but their
      pathogeneses are fundamentally diverse. Distinguishing SIADH from CSW is based on
      the differential diagnoses of dilutional hyponatremia due to an excessive amount
      of water in the body (SIADH) and depletional hyponatremia caused by extensive
      natriuresis (CSW). METHODS AND RESULTS: We report the case of a 48-year-old,
      previously healthy male with a diffuse large B-cell lymphoma affecting the area
      of the basal ganglia and the right part of the thalamus and oppressing the third
      brain ventricle. After admission to the Department of Hemato-oncology, the
      patient was soporous and laboratory tests revealed severe serum hyponatremia,
      hypochloremia, hypoosmolality and marked polyuria with normal serum levels of
      urea, creatinine, glucose and calcium. Urinalysis showed high specific gravity of
      the urine and extreme wasting of sodium, chloride and kalium ions. Overall fluid
      balance was negative. After the first chemotherapy cycle, the CT scan confirmed
      regression of the tumour site. This was accompanied by patient's improved
      cognition as well as decreased polyuria and urine electrolyte excretion.
      Eventually, it was concluded that the diagnosis was cerebral salt wasting
      syndrome. CONCLUSION: We noted a so far unpublished case of a 48-year-old male
      with the diagnosis of primary CNS lymphoma (DLBCL) affecting deep structures of
      the brain and associated with CSW.

PMID- 19851437
TI  - Expulsive hemorrhage after glaucoma filtering surgery.
AB  - AIMS: To evaluate the incidence, patient risk factors, diagnosis and management
      of suprachoroidal hemorrhage (SCH) after glaucoma filtering surgery. METHODS:
      Retrospective case series study comprised 1553 eyes having glaucoma filtering
      surgery during the last 15 years (between January 1993 and December 2007) at our
      department. Observations included incidence, patient risk factors, peri and
      postoperative diagnosis, management, and outcomes of SCH after this procedure.
      RESULTS: Two cases of SCH were revealed. In one eye SCH developed at the end of
      surgery, in the other eye in the postoperative period. Both patients had systemic
      and ocular risk factors (hypertension, high preoperative intraocular pressure,
      myopia, pseudoexfoliation, aphakia or pseudophakia). Visual functions improved in
      the case of intraoperative SCH over 2 months withouth surgical intervention, in
      the eye with delayed postoperative SCH visual outcome was poor despite multiple
      lavages of anterior chamber and vitreous cavity. CONCLUSION: Suprachoroidal
      hemorrhage, both expulsive and delayed, is a rare, but severely debilitating
      complication of glaucoma surgery.

PMID- 19851438
TI  - Is the dorsal percutaneous approach well-founded for osteosynthesis of scaphoid
      fractures?
AB  - AIMS: To compare complications associated with dorsal percutaneous and limited
      dorsal approaches in the surgical treatment of fractured scaphoid bone. METHODS:
      A total of 51 patients with acute type A2, B2 and B3 scaphoid fractures were
      treated by limited dorsal approach. During follow-up examinations we analysed the
      functional outcome and per- and post-operative complications, and we compared
      them with studies using the dorsal percutaneous approach. RESULTS: We found fewer
      complications using the limited dorsal approach. CONCLUSIONS: We found no
      advantages of the dorsal percutaneous approach. In addition to a favourable
      functional outcome, the limited dorsal approach permits visualization of the
      screw insertion point and of the fracture line course, and prevents insufficient
      screw sinking underneath the bone cartilage and malunion.

PMID- 19851439
TI  - Association among size of thymus, anthropometric dimensions and number of
      lymphocytes in peripheral blood in newborns from Slovakia.
AB  - AIMS: Thymus is the central lymphatic organ in humans with important endocrine
      function that is involved in maturation of immunocompetent T-lymphocytes. In our
      study we investigated the relationship among thymus size and the anthropometric
      dimensions as well as between thymus size and the number of lymphocytes in
      peripheral blood in full-term newborns. METHODS: The examined group consisted of
      212 full-term newborns from the region of Southern Slovakia. We examined birth
      weight, birth body length, head circumference and chest circumference. Thymus
      size was estimated by ultrasonography and it was expressed as Thymic Index. The
      number of lymphocytes in peripheral blood was determined from the number of total
      leukocytes and from the leukogram. RESULTS: We have found a statistically
      significant positive correlation among thymus size and the body dimensions of
      newborns. The highest correlation with thymus size was found for birth weight (r
      = 0.409; P < 0.001) followed by birth body length (r = 0.368; P < 0.001), head
      circumference (r = 0.365; P < 0.001) and chest circumference (r = 0.340; P <
      0.001). We have proven also a statistically significant positive correlation
      between the number of lymphocytes in peripheral blood and thymus size (r = 0.208;
      P = 0.039). CONCLUSION: Our results confirmed the findings of other authors about
      a close relationship of Thymic Index and basic body parameters in newborns.

PMID- 19851440
TI  - The new from the old.

PMID- 19851441
TI  - An atlas of the thioredoxin fold class reveals the complexity of function
      enabling adaptations.
AB  - The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse.
      Assessment of the variation in catalytic machinery of Trx fold proteins is
      essential in providing a foundation for understanding their functional diversity
      and predicting the function of the many uncharacterized members of the class. The
      proteins of the Trx fold class retain common features-including variations on a
      dithiol CxxC active site motif-that lead to delivery of function. We use protein
      similarity networks to guide an analysis of how structural and sequence motifs
      track with catalytic function and taxonomic categories for 4,082 representative
      sequences spanning the known superfamilies of the Trx fold. Domain structure in
      the fold class is varied and modular, with 2.8% of sequences containing more than
      one Trx fold domain. Most member proteins are bacterial. The fold class exhibits
      many modifications to the CxxC active site motif-only 56.8% of proteins have both
      cysteines, and no functional groupings have absolute conservation of the expected
      catalytic motif. Only a small fraction of Trx fold sequences have been
      functionally characterized. This work provides a global view of the complex
      distribution of domains and catalytic machinery throughout the fold class,
      showing that each superfamily contains remnants of the CxxC active site. The
      unifying context provided by this work can guide the comparison of members of
      different Trx fold superfamilies to gain insight about their structure-function
      relationships, illustrated here with the thioredoxins and peroxiredoxins.

PMID- 19851442
TI  - Meta-analysis of the INSIG2 association with obesity including 74,345
      individuals: does heterogeneity of estimates relate to study design?
AB  - The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30
      kg/m(2)) in one of the first genome-wide association studies, but replications
      were inconsistent. We collected statistics from 34 studies (n = 74,345),
      including general population (GP) studies, population-based studies with subjects
      selected for conditions related to a better health status ('healthy population',
      HP), and obesity studies (OB). We tested five hypotheses to explore potential
      sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n
      = 66,213) combining the different study designs did not support overall
      association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05
      (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between
      study heterogeneity. Restricting to GP studies resulted in a declined I(2)
      measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding
      the five hypotheses, our data showed (a) some difference between GP and HP
      studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or
      =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16,
      1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by
      significantly increased CC-genotype frequencies across BMI categories (10.4% to
      12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs
      (c) among studies with higher than average obesity prevalence compared to lower,
      (d) among studies with BMI assessment after the year 2000 compared to those
      before, or (e) among studies from older populations compared to younger. Analysis
      of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p
      value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for
      overall association of the rs7566605 polymorphism with obesity. Our data
      suggested an association with extreme degrees of obesity, and consequently
      heterogeneous effects from different study designs may mask an underlying
      association when unaccounted for. The importance of study design might be under
      recognized in gene discovery and association replication so far.

PMID- 19851443
TI  - Invariant distribution of promoter activities in Escherichia coli.
AB  - Cells need to allocate their limited resources to express a wide range of genes.
      To understand how Escherichia coli partitions its transcriptional resources
      between its different promoters, we employ a robotic assay using a comprehensive
      reporter strain library for E. coli to measure promoter activity on a genomic
      scale at high-temporal resolution and accuracy. This allows continuous tracking
      of promoter activity as cells change their growth rate from exponential to
      stationary phase in different media. We find a heavy-tailed distribution of
      promoter activities, with promoter activities spanning several orders of
      magnitude. While the shape of the distribution is almost completely independent
      of the growth conditions, the identity of the promoters expressed at different
      levels does depend on them. Translation machinery genes, however, keep the same
      relative expression levels in the distribution across conditions, and their
      fractional promoter activity tracks growth rate tightly. We present a simple
      optimization model for resource allocation which suggests that the observed
      invariant distributions might maximize growth rate. These invariant features of
      the distribution of promoter activities may suggest design constraints that shape
      the allocation of transcriptional resources.

PMID- 19851444
TI  - Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation
      of the DNA damage checkpoint and elevation of dNTP levels.
AB  - Peroxiredoxins are a family of antioxidant enzymes critically involved in
      cellular defense and signaling. Particularly, yeast peroxiredoxin Tsa1p is
      thought to play a role in the maintenance of genome integrity, but the underlying
      mechanism is not understood. In this study, we took a genetic approach to
      investigate the cause of genome instability in tsa1Delta cells. Strong genetic
      interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1
      were found when mutant cells were analyzed for either sensitivity to DNA damage
      or rate of spontaneous base substitutions. An elevation in intracellular dNTP
      production was observed in tsa1Delta cells. This was associated with constitutive
      activation of the DNA damage checkpoint as indicated by phosphorylation of
      Rad9/Rad53p, reduced steady-state amount of Sml1p, and induction of RNR and HUG1
      genes. In addition, defects in the DNA damage checkpoint did not modulate
      intracellular level of reactive oxygen species, but suppressed the mutator
      phenotype of tsa1Delta cells. On the contrary, overexpression of RNR1 exacerbated
      this phenotype by increasing dNTP levels. Taken together, our findings uncover a
      new role of TSA1 in preventing the overproduction of dNTPs, which is a root cause
      of genome instability.

PMID- 19851445
TI  - High-density SNP screening of the major histocompatibility complex in systemic
      lupus erythematosus demonstrates strong evidence for independent susceptibility
      regions.
AB  - A substantial genetic contribution to systemic lupus erythematosus (SLE) risk is
      conferred by major histocompatibility complex (MHC) gene(s) on chromosome 6p21.
      Previous studies in SLE have lacked statistical power and genetic resolution to
      fully define MHC influences. We characterized 1,610 Caucasian SLE cases and 1,470
      parents for 1,974 MHC SNPs, the highly polymorphic HLA-DRB1 locus, and a panel of
      ancestry informative markers. Single-marker analyses revealed strong signals for
      SNPs within several MHC regions, as well as with HLA-DRB1 (global p = 9.99 x 10(
      16)). The most strongly associated DRB1 alleles were: *0301 (odds ratio, OR =
      2.21, p = 2.53 x 10(-12)), *1401 (OR = 0.50, p = 0.0002), and *1501 (OR = 1.39, p
      = 0.0032). The MHC region SNP demonstrating the strongest evidence of association
      with SLE was rs3117103, with OR = 2.44 and p = 2.80 x 10(-13). Conditional
      haplotype and stepwise logistic regression analyses identified strong evidence
      for association between SLE and the extended class I, class I, class III, class
      II, and the extended class II MHC regions. Sequential removal of SLE-associated
      DRB1 haplotypes revealed independent effects due to variation within OR2H2
      (extended class I, rs362521, p = 0.006), CREBL1 (class III, rs8283, p = 0.01),
      and DQB2 (class II, rs7769979, p = 0.003, and rs10947345, p = 0.0004). Further,
      conditional haplotype analyses demonstrated that variation within MICB (class I,
      rs3828903, p = 0.006) also contributes to SLE risk independent of HLA-DRB1*0301.
      Our results for the first time delineate with high resolution several MHC regions
      with independent contributions to SLE risk. We provide a list of candidate
      variants based on biologic and functional considerations that may be causally
      related to SLE risk and warrant further investigation.

PMID- 19851446
TI  - Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are
      depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase.
AB  - Meiotic crossovers are produced when programmed double-strand breaks (DSBs) are
      repaired by recombination from homologous chromosomes (homologues). In a wide
      variety of organisms, meiotic HORMA-domain proteins are required to direct DSB
      repair towards homologues. This inter-homologue bias is required for efficient
      homology search, homologue alignment, and crossover formation. HORMA-domain
      proteins are also implicated in other processes related to crossover formation,
      including DSB formation, inhibition of promiscuous formation of the synaptonemal
      complex (SC), and the meiotic prophase checkpoint that monitors both DSB
      processing and SCs. We examined the behavior of two previously uncharacterized
      meiosis-specific mouse HORMA-domain proteins--HORMAD1 and HORMAD2--in wild-type
      mice and in mutants defective in DSB processing or SC formation. HORMADs are
      preferentially associated with unsynapsed chromosome axes throughout meiotic
      prophase. We observe a strong negative correlation between SC formation and
      presence of HORMADs on axes, and a positive correlation between the presumptive
      sites of high checkpoint-kinase ATR activity and hyper-accumulation of HORMADs on
      axes. HORMADs are not depleted from chromosomes in mutants that lack SCs. In
      contrast, DSB formation and DSB repair are not absolutely required for depletion
      of HORMADs from synapsed axes. A simple interpretation of these findings is that
      SC formation directly or indirectly promotes depletion of HORMADs from chromosome
      axes. We also find that TRIP13 protein is required for reciprocal distribution of
      HORMADs and the SYCP1/SC-component along chromosome axes. Similarities in mouse
      and budding yeast meiosis suggest that TRIP13/Pch2 proteins have a conserved role
      in establishing mutually exclusive HORMAD-rich and synapsed chromatin domains in
      both mouse and yeast. Taken together, our observations raise the possibility that
      involvement of meiotic HORMA-domain proteins in the regulation of homologue
      interactions is conserved in mammals.

PMID- 19851447
TI  - Perturbation-response scanning reveals ligand entry-exit mechanisms of ferric
      binding protein.
AB  - We study apo and holo forms of the bacterial ferric binding protein (FBP) which
      exhibits the so-called ferric transport dilemma: it uptakes iron from the host
      with remarkable affinity, yet releases it with ease in the cytoplasm for
      subsequent use. The observations fit the "conformational selection" model whereby
      the existence of a weakly populated, higher energy conformation that is
      stabilized in the presence of the ligand is proposed. We introduce a new tool
      that we term perturbation-response scanning (PRS) for the analysis of remote
      control strategies utilized. The approach relies on the systematic use of
      computational perturbation/response techniques based on linear response theory,
      by sequentially applying directed forces on single-residues along the chain and
      recording the resulting relative changes in the residue coordinates. We further
      obtain closed-form expressions for the magnitude and the directionality of the
      response. Using PRS, we study the ligand release mechanisms of FBP and support
      the findings by molecular dynamics simulations. We find that the residue-by
      residue displacements between the apo and the holo forms, as determined from the
      X-ray structures, are faithfully reproduced by perturbations applied on the
      majority of the residues of the apo form. However, once the stabilizing ligand
      (Fe) is integrated to the system in holo FBP, perturbing only a few select
      residues successfully reproduces the experimental displacements. Thus, iron
      uptake by FBP is a favored process in the fluctuating environment of the protein,
      whereas iron release is controlled by mechanisms including chelation and
      allostery. The directional analysis that we implement in the PRS methodology
      implicates the latter mechanism by leading to a few distant, charged, and exposed
      loop residues. Upon perturbing these, irrespective of the direction of the
      operating forces, we find that the cap residues involved in iron release are made
      to operate coherently, facilitating release of the ion.

PMID- 19851448
TI  - Quantifying adaptive evolution in the Drosophila immune system.
AB  - It is estimated that a large proportion of amino acid substitutions in Drosophila
      have been fixed by natural selection, and as organisms are faced with an ever
      changing array of pathogens and parasites to which they must adapt, we have
      investigated the role of parasite-mediated selection as a likely cause. To
      quantify the effect, and to identify which genes and pathways are most likely to
      be involved in the host-parasite arms race, we have re-sequenced population
      samples of 136 immunity and 287 position-matched non-immunity genes in two
      species of Drosophila. Using these data, and a new extension of the McDonald
      Kreitman approach, we estimate that natural selection fixes advantageous amino
      acid changes in immunity genes at nearly double the rate of other genes. We find
      the rate of adaptive evolution in immunity genes is also more variable than other
      genes, with a small subset of immune genes evolving under intense selection.
      These genes, which are likely to represent hotspots of host-parasite coevolution,
      tend to share similar functions or belong to the same pathways, such as the
      antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to
      be general features of immune system evolution in both species, as rates of
      adaptive evolution are correlated between the D. melanogaster and D. simulans
      lineages. In summary, our data provide quantitative estimates of the elevated
      rate of adaptive evolution in immune system genes relative to the rest of the
      genome, and they suggest that adaptation to parasites is an important force
      driving molecular evolution.

PMID- 19851449
TI  - Steps in the bacterial flagellar motor.
AB  - The bacterial flagellar motor is a highly efficient rotary machine used by many
      bacteria to propel themselves. It has recently been shown that at low speeds its
      rotation proceeds in steps. Here we propose a simple physical model, based on the
      storage of energy in protein springs, that accounts for this stepping behavior as
      a random walk in a tilted corrugated potential that combines torque and contact
      forces. We argue that the absolute angular position of the rotor is crucial for
      understanding step properties and show this hypothesis to be consistent with the
      available data, in particular the observation that backward steps are smaller on
      average than forward steps. We also predict a sublinear speed versus torque
      relationship for fixed load at low torque, and a peak in rotor diffusion as a
      function of torque. Our model provides a comprehensive framework for
      understanding and analyzing stepping behavior in the bacterial flagellar motor
      and proposes novel, testable predictions. More broadly, the storage of energy in
      protein springs by the flagellar motor may provide useful general insights into
      the design of highly efficient molecular machines.

PMID- 19851450
TI  - A model of cardiovascular disease giving a plausible mechanism for the effect of
      fractionated low-dose ionizing radiation exposure.
AB  - Atherosclerosis is the main cause of coronary heart disease and stroke, the two
      major causes of death in developed society. There is emerging evidence of excess
      risk of cardiovascular disease at low radiation doses in various occupationally
      exposed groups receiving small daily radiation doses. Assuming that they are
      causal, the mechanisms for effects of chronic fractionated radiation exposures on
      cardiovascular disease are unclear. We outline a spatial reaction-diffusion model
      for atherosclerosis and perform stability analysis, based wherever possible on
      human data. We show that a predicted consequence of multiple small radiation
      doses is to cause mean chemo-attractant (MCP-1) concentration to increase
      linearly with cumulative dose. The main driver for the increase in MCP-1 is
      monocyte death, and consequent reduction in MCP-1 degradation. The radiation
      induced risks predicted by the model are quantitatively consistent with those
      observed in a number of occupationally-exposed groups. The changes in equilibrium
      MCP-1 concentrations with low density lipoprotein cholesterol concentration are
      also consistent with experimental and epidemiologic data. This proposed mechanism
      would be experimentally testable. If true, it also has substantive implications
      for radiological protection, which at present does not take cardiovascular
      disease into account. The Japanese A-bomb survivor data implies that
      cardiovascular disease and cancer mortality contribute similarly to radiogenic
      risk. The major uncertainty in assessing the low-dose risk of cardiovascular
      disease is the shape of the dose response relationship, which is unclear in the
      Japanese data. The analysis of the present paper suggests that linear
      extrapolation would be appropriate for this endpoint.

PMID- 19851451
TI  - Bacterial porin disrupts mitochondrial membrane potential and sensitizes host
      cells to apoptosis.
AB  - The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic
      Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB
      is targeted to and imported by host cell mitochondria, causing the breakdown of
      the mitochondrial membrane potential (DeltaPsi(m)). Here, we show that PorB
      induces the condensation of the mitochondrial matrix and the loss of cristae
      structures, sensitizing cells to the induction of apoptosis via signaling
      pathways activated by BH3-only proteins. PorB is imported into mitochondria
      through the general translocase TOM but, unexpectedly, is not recognized by the
      SAM sorting machinery, usually required for the assembly of beta-barrel proteins
      in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner
      membrane, leading to the breakdown of DeltaPsi(m). The PorB channel is regulated
      by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to
      induce DeltaPsi(m) loss and apoptosis, demonstrating that dissipation of
      DeltaPsi(m) is a requirement for cell death caused by neisserial infection.

PMID- 19851452
TI  - Wolbachia interferes with ferritin expression and iron metabolism in insects.
AB  - Wolbachia is an intracellular bacterium generally described as being a
      facultative reproductive parasite. However, Wolbachia is necessary for oogenesis
      completion in the wasp Asobara tabida. This dependence has evolved recently as a
      result of interference with apoptosis during oogenesis. Through comparative
      transcriptomics between symbiotic and aposymbiotic individuals, we observed a
      differential expression of ferritin, which forms a complex involved in iron
      storage. Iron is an essential element that is in limited supply in the cell.
      However, it is also a highly toxic precursor of Reactive Oxygen Species (ROS).
      Ferritin has also been shown to play a key role in host-pathogen interactions.
      Measuring ferritin by quantitative RT-PCR, we confirmed that ferritin was
      upregulated in aposymbiotic compared to symbiotic individuals. Manipulating the
      iron content in the diet, we showed that iron overload markedly affected wasp
      development and induced apoptotic processes during oogenesis in A. tabida,
      suggesting that the regulation of iron homeostasis may also be related to the
      obligate dependence of the wasp. Finally, we demonstrated that iron metabolism is
      influenced by the presence of Wolbachia not only in the obligate mutualism with
      A. tabida, but also in facultative parasitism involving Drosophila simulans and
      in Aedes aegypti cells. In these latter cases, the expression of Wolbachia
      bacterioferritin was also increased in the presence of iron, showing that
      Wolbachia responds to the concentration of iron. Our results indicate that
      Wolbachia may generally interfere with iron metabolism. The high affinity of
      Wolbachia for iron might be due to physiological requirement of the bacterium,
      but it could also be what allows the symbiont to persist in the organism by
      reducing the labile iron concentration, thus protecting the cell from oxidative
      stress and apoptosis. These findings also reinforce the idea that pathogenic,
      parasitic and mutualistic intracellular bacteria all use the same molecular
      mechanisms to survive and replicate within host cells. By impacting the general
      physiology of the host, the presence of a symbiont may select for host
      compensatory mechanisms, which extends the possible consequences of persistent
      endosymbiont on the evolution of their hosts.

PMID- 19851453
TI  - A distinct peripheral blood monocyte phenotype is associated with parasite
      inhibitory activity in acute uncomplicated Plasmodium falciparum malaria.
AB  - Monocyte (MO) subpopulations display distinct phenotypes and functions which can
      drastically change during inflammatory states. We hypothesized that discrete MO
      subpopulations are induced during malaria infection and associated with anti
      parasitic activity. We characterized the phenotype of blood MO from healthy
      malaria-exposed individuals and that of patients with acute uncomplicated malaria
      by flow cytometry. In addition, MO defense function was evaluated by an in vitro
      antibody dependent cellular inhibition (ADCI) assay. At the time of admission,
      the percentages and absolute numbers of CD16+ MO, and CCR2+CX3CR1+ MO, were high
      in a majority of patients. Remarkably, expression of CCR2 and CX3CR1 on the
      CD14(high (hi)) MO subset defined two subgroups of patients that also differed
      significantly in their functional ability to limit the parasite growth, through
      the ADCI mechanism. In the group of patients with the highest percentages and
      absolute numbers of CD14(hi)CCR2+CX3CR1+ MO and the highest mean levels of ADCI
      activity, blood parasitemias were lower (0.14+/-0.34%) than in the second group
      (1.30+/-3.34%; p = 0.0053). Data showed that, during a malaria attack, some
      patients' MO can exert a strong ADCI activity. These results bring new insight
      into the complex relationships between the phenotype and the functional activity
      of blood MO from patients and healthy malaria-exposed individuals and suggest
      discrete MO subpopulations are induced during malaria infection and are
      associated with anti-parasitic activity.

PMID- 19851454
TI  - 1+1 = 3: a fusion of 2 enzymes in the methionine salvage pathway of Tetrahymena
      thermophila creates a trifunctional enzyme that catalyzes 3 steps in the pathway.
AB  - The methionine salvage pathway is responsible for regenerating methionine from
      its derivative, methylthioadenosine. The complete set of enzymes of the
      methionine pathway has been previously described in bacteria. Despite its
      importance, the pathway has only been fully described in one eukaryotic organism,
      yeast. Here we use a computational approach to identify the enzymes of the
      methionine salvage pathway in another eukaryote, Tetrahymena thermophila. In this
      organism, the pathway has two fused genes, MTNAK and MTNBD. Each of these fusions
      involves two different genes whose products catalyze two different single steps
      of the pathway in other organisms. One of the fusion proteins, mtnBD, is formed
      by enzymes that catalyze non-consecutive steps in the pathway, mtnB and mtnD.
      Interestingly the gene that codes for the intervening enzyme in the pathway,
      mtnC, is missing from the genome of Tetrahymena. We used complementation tests in
      yeast to show that the fusion of mtnB and mtnD from Tetrahymena is able to do in
      one step what yeast does in three, since it can rescue yeast knockouts of mtnB,
      mtnC, or mtnD. Fusion genes have proved to be very useful in aiding phylogenetic
      reconstructions and in the functional characterization of genes. Our results
      highlight another characteristic of fusion proteins, namely that these proteins
      can serve as biochemical shortcuts, allowing organisms to completely bypass steps
      in biochemical pathways.

PMID- 19851455
TI  - Bruchpilot in ribbon-like axonal agglomerates, behavioral defects, and early
      death in SRPK79D kinase mutants of Drosophila.
AB  - Defining the molecular structure and function of synapses is a central theme in
      brain research. In Drosophila the Bruchpilot (BRP) protein is associated with T
      shaped ribbons ("T-bars") at presynaptic active zones (AZs). BRP is required for
      intact AZ structure and normal evoked neurotransmitter release. By screening for
      mutations that affect the tissue distribution of Bruchpilot, we have identified a
      P-transposon insertion in gene CG11489 (location 79D) which shows high homology
      to mammalian genes for SR protein kinases (SRPKs). SRPKs phosphorylate serine
      arginine rich splicing factors (SR proteins). Since proteins expressed from
      CG11489 cDNAs phosphorylate a peptide from a human SR protein in vitro, we name
      CG11489 the Drosophila Srpk79D gene. We have characterized Srpk79D transcripts
      and generated a null mutant. Mutation of the Srpk79D gene causes conspicuous
      accumulations of BRP in larval and adult nerves. At the ultrastructural level,
      these correspond to extensive axonal agglomerates of electron-dense ribbons
      surrounded by clear vesicles. Basic synaptic structure and function at larval
      neuromuscular junctions appears normal, whereas life expectancy and locomotor
      behavior of adult mutants are significantly impaired. All phenotypes of the
      mutant can be largely or completely rescued by panneural expression of SRPK79D
      isoforms. Isoform-specific antibodies recognize panneurally overexpressed GFP
      tagged SRPK79D-PC isoform co-localized with BRP at presynaptic active zones while
      the tagged -PB isoform is found in spots within neuronal perikarya. SRPK79D
      concentrations in wild type apparently are too low to be revealed by these
      antisera. We propose that the Drosophila Srpk79D gene characterized here may be
      expressed at low levels throughout the nervous system to prevent the assembly of
      BRP containing agglomerates in axons and maintain intact brain function. The
      discovery of an SR protein kinase required for normal BRP distribution calls for
      the identification of its substrate and the detailed analysis of SRPK function
      for the maintenance of nervous system integrity.

PMID- 19851456
TI  - Dengue virus capsid protein usurps lipid droplets for viral particle formation.
AB  - Dengue virus is responsible for the highest rates of disease and mortality among
      the members of the Flavivirus genus. Dengue epidemics are still occurring around
      the world, indicating an urgent need of prophylactic vaccines and antivirals. In
      recent years, a great deal has been learned about the mechanisms of dengue virus
      genome amplification. However, little is known about the process by which the
      capsid protein recruits the viral genome during encapsidation. Here, we found
      that the mature capsid protein in the cytoplasm of dengue virus infected cells
      accumulates on the surface of ER-derived organelles named lipid droplets.
      Mutagenesis analysis using infectious dengue virus clones has identified specific
      hydrophobic amino acids, located in the center of the capsid protein, as key
      elements for lipid droplet association. Substitutions of amino acid L50 or L54 in
      the capsid protein disrupted lipid droplet targeting and impaired viral particle
      formation. We also report that dengue virus infection increases the number of
      lipid droplets per cell, suggesting a link between lipid droplet metabolism and
      viral replication. In this regard, we found that pharmacological manipulation of
      the amount of lipid droplets in the cell can be a means to control dengue virus
      replication. In addition, we developed a novel genetic system to dissociate cis
      acting RNA replication elements from the capsid coding sequence. Using this
      system, we found that mislocalization of a mutated capsid protein decreased viral
      RNA amplification. We propose that lipid droplets play multiple roles during the
      viral life cycle; they could sequester the viral capsid protein early during
      infection and provide a scaffold for genome encapsidation.

PMID- 19851457
TI  - Evolutionary dynamics of human rotaviruses: balancing reassortment with preferred
      genome constellations.
AB  - Group A human rotaviruses (RVs) are a major cause of severe gastroenteritis in
      infants and young children. Yet, aside from the genes encoding serotype antigens
      (VP7; G-type and VP4; P-type), little is known about the genetic make-up of
      emerging and endemic human RV strains. To gain insight into the diversity and
      evolution of RVs circulating at a single location over a period of time, we
      sequenced the eleven-segmented, double-stranded RNA genomes of fifty-one G3P[8]
      strains collected from 1974 to 1991 at Children's Hospital National Medical
      Center, Washington, D. C. During this period, G1P[8] strains typically dominated,
      comprising on average 56% of RV infections each year in hospitalized children. A
      notable exception was in the 1976 and 1991 winter seasons when the incidence of
      G1P[8] infections decreased dramatically, a trend that correlated with a
      significant increase in G3P[8] infections. Our sequence analysis indicates that
      the 1976 season was characterized by the presence of several genetically
      distinct, co-circulating clades of G3P[8] viruses, which contained minor but
      significant differences in their encoded proteins. These 1976 lineages did not
      readily exchange gene segments with each other, but instead remained stable over
      the course of the season. In contrast, the 1991 season contained a single major
      clade, whose genome constellation was similar to one of the 1976 clades. The 1991
      clade may have gained a fitness advantage after reassorting with as of yet
      unidentified RV strain(s). This study reveals for the first time that genetically
      distinct RV clades of the same G/P-type can co-circulate and cause disease. The
      findings from this study also suggest that, although gene segment exchange
      occurs, most reassortant strains are replaced over time by lineages with
      preferred genome constellations. Elucidation of the selective pressures that
      favor maintenance of RVs with certain sets of genes may be necessary to
      anticipate future vaccine needs.

PMID- 19851458
TI  - The HIV envelope but not VSV glycoprotein is capable of mediating HIV latent
      infection of resting CD4 T cells.
AB  - HIV fusion and entry into CD4 T cells are mediated by two receptors, CD4 and
      CXCR4. This receptor requirement can be abrogated by pseudotyping the virion with
      the vesicular stomatitis virus glycoprotein (VSV-G) that mediates viral entry
      through endocytosis. The VSV-G-pseudotyped HIV is highly infectious for
      transformed cells, although the virus circumvents the viral receptors and the
      actin cortex. In HIV infection, gp120 binding to the receptors also transduces
      signals. Recently, we demonstrated a unique requirement for CXCR4 signaling in
      HIV latent infection of blood resting CD4 T cells. Thus, we performed parallel
      studies in which the VSV-G-pseudotyped HIV was used to infect both transformed
      and resting T cells in the absence of coreceptor signaling. Our results indicate
      that in transformed T cells, the VSV-G-pseudotyping results in lower viral DNA
      synthesis but a higher rate of nuclear migration. However, in resting CD4 T
      cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated
      endocytosis, can lead to viral DNA synthesis and nuclear migration. The viral
      particles entering through the endocytotic pathway were destroyed within 1-2
      days. These results indicate that the VSV-G-mediated endocytotic pathway,
      although active in transformed cells, is defective and is not a pathway that can
      establish HIV latent infection of primary resting T cells. Our results highlight
      the importance of the genuine HIV envelope and its signaling capacity in the
      latent infection of blood resting T cells. These results also call for caution on
      the endocytotic entry model of HIV-1, and on data interpretation where the VSV-G
      pseudotyped HIV was used for identifying HIV restriction factors in resting T
      cells.

PMID- 19851459
TI  - Restricting dosage compensation complex binding to the X chromosomes by H2A.Z/HTZ
      1.
AB  - Dosage compensation ensures similar levels of X-linked gene products in males (XY
      or XO) and females (XX), despite their different numbers of X chromosomes. In
      mammals, flies, and worms, dosage compensation is mediated by a specialized
      machinery that localizes to one or both of the X chromosomes in one sex resulting
      in a change in gene expression from the affected X chromosome(s). In mammals and
      flies, dosage compensation is associated with specific histone posttranslational
      modifications and replacement with variant histones. Until now, no specific
      histone modifications or histone variants have been implicated in Caenorhabditis
      elegans dosage compensation. Taking a candidate approach, we have looked at
      specific histone modifications and variants on the C. elegans dosage compensated
      X chromosomes. Using RNAi-based assays, we show that reducing levels of the
      histone H2A variant, H2A.Z (HTZ-1 in C. elegans), leads to partial disruption of
      dosage compensation. By immunofluorescence, we have observed that HTZ-1 is under
      represented on the dosage compensated X chromosomes, but not on the non-dosage
      compensated male X chromosome. We find that reduction of HTZ-1 levels by RNA
      interference (RNAi) and mutation results in only a very modest change in dosage
      compensation complex protein levels. However, in these animals, the X chromosome
      specific localization of the complex is partially disrupted, with some nuclei
      displaying DCC localization beyond the X chromosome territory. We propose a model
      in which HTZ-1, directly or indirectly, serves to restrict the dosage
      compensation complex to the X chromosome by acting as or regulating the activity
      of an autosomal repellant.

PMID- 19851460
TI  - Inferring the joint demographic history of multiple populations from
      multidimensional SNP frequency data.
AB  - Demographic models built from genetic data play important roles in illuminating
      prehistorical events and serving as null models in genome scans for selection. We
      introduce an inference method based on the joint frequency spectrum of genetic
      variants within and between populations. For candidate models we numerically
      compute the expected spectrum using a diffusion approximation to the one-locus,
      two-allele Wright-Fisher process, involving up to three simultaneous populations.
      Our approach is a composite likelihood scheme, since linkage between neutral loci
      alters the variance but not the expectation of the frequency spectrum. We thus
      use bootstraps incorporating linkage to estimate uncertainties for parameters and
      significance values for hypothesis tests. Our method can also incorporate
      selection on single sites, predicting the joint distribution of selected alleles
      among populations experiencing a bevy of evolutionary forces, including
      expansions, contractions, migrations, and admixture. We model human expansion out
      of Africa and the settlement of the New World, using 5 Mb of noncoding DNA
      resequenced in 68 individuals from 4 populations (YRI, CHB, CEU, and MXL) by the
      Environmental Genome Project. We infer divergence between West African and
      Eurasian populations 140 thousand years ago (95% confidence interval: 40-270
      kya). This is earlier than other genetic studies, in part because we incorporate
      migration. We estimate the European (CEU) and East Asian (CHB) divergence time to
      be 23 kya (95% c.i.: 17-43 kya), long after archeological evidence places modern
      humans in Europe. Finally, we estimate divergence between East Asians (CHB) and
      Mexican-Americans (MXL) of 22 kya (95% c.i.: 16.3-26.9 kya), and our analysis
      yields no evidence for subsequent migration. Furthermore, combining our
      demographic model with a previously estimated distribution of selective effects
      among newly arising amino acid mutations accurately predicts the frequency
      spectrum of nonsynonymous variants across three continental populations (YRI,
      CHB, CEU).

PMID- 19851461
TI  - The secretion of areolar (Montgomery's) glands from lactating women elicits
      selective, unconditional responses in neonates.
AB  - BACKGROUND: The communicative meaning of human areolae for newborn infants was
      examined here in directly exposing 3-day old neonates to the secretion from the
      areolar glands of Montgomery donated by non related, non familiar lactating
      women. METHODOLOGY/PRINCIPAL FINDINGS: The effect of the areolar stimulus on the
      infants' behavior and autonomic nervous system was compared to that of seven
      reference stimuli originating either from human or non human mammalian sources,
      or from an arbitrarily-chosen artificial odorant. The odor of the native areolar
      secretion intensified more than all other stimuli the infants' inspiratory
      activity and appetitive oral responses. These responses appeared to develop
      independently from direct experience with the breast or milk.
      CONCLUSION/SIGNIFICANCE: Areolar secretions from lactating women are especially
      salient to human newborns. Volatile compounds carried in these substrates are
      thus in a position to play a key role in establishing behavioral and
      physiological processes pertaining to milk transfer and production, and, hence,
      to survival and to the early engagement of attachment and bonding.

PMID- 19851462
TI  - EB1 recognizes the nucleotide state of tubulin in the microtubule lattice.
AB  - Plus-end-tracking proteins (+TIPs) are localized at the fast-growing, or plus
      end, of microtubules, and link microtubule ends to cellular structures. One of
      the best studied +TIPs is EB1, which forms comet-like structures at the tips of
      growing microtubules. The molecular mechanisms by which EB1 recognizes and tracks
      growing microtubule ends are largely unknown. However, one clue is that EB1 can
      bind directly to a microtubule end in the absence of other proteins. Here we use
      an in vitro assay for dynamic microtubule growth with two-color total-internal
      reflection-fluorescence imaging to investigate binding of mammalian EB1 to both
      stabilized and dynamic microtubules. We find that under conditions of microtubule
      growth, EB1 not only tip tracks, as previously shown, but also preferentially
      recognizes the GMPCPP microtubule lattice as opposed to the GDP lattice. The
      interaction of EB1 with the GMPCPP microtubule lattice depends on the E-hook of
      tubulin, as well as the amount of salt in solution. The ability to distinguish
      different nucleotide states of tubulin in microtubule lattice may contribute to
      the end-tracking mechanism of EB1.

PMID- 19851463
TI  - Lymphoid EVA1 expression is required for DN1-DN3 thymocytes transition.
AB  - BACKGROUND: Thymus organogenesis and T lymphocyte development are accomplished
      together during fetal life. Proper development and maintenance of thymus
      architecture depend on signals generated by a sustained crosstalk between
      developing thymocytes and stromal elements. Any maturation impairment occurring
      in either cellular component leads to an aberrant thymic development. Gene
      expression occurring during T lymphocyte differentiation must be coordinated in a
      spatio-temporal fashion; one way in which this is achieved is through the
      regulation by cell-cell adhesion and interactions. PRINCIPAL FINDINGS: We
      examined the role played by Epithelial V-like Antigen 1 (EVA1), an Ig adhesion
      molecule expressed on thymus epithelial cells (TEC) and immature thymocytes, in T
      cell development by employing RNA interference in vitro and in vivo models. Fetal
      liver derived haematopoietic progenitors depleted of Eva1, displayed a delayed
      DN1-DN3 transition and failed to generate CD4CD8 double positive T cells in OP9
      DL1 coculture system. In addition, we could observe a coordinated Eva1 up
      regulation in stromal and haematopoietic cells in coculture control experiments,
      suggesting a possible EVA1 involvement in TEC-haematopoietic cells crosstalk
      mechanisms. Similarly, Rag2-gamma c double knock out mice, transplanted with Eva1
      depleted haematopoietic progenitors displayed a 10-fold reduction in thymus
      reconstitution and a time delayed thymocytes maturation compared to controls.
      CONCLUSIONS: Our findings show that modulation of Eva1 expression in thymocytes
      is crucial for lymphocyte physiological developmental progression and stromal
      differentiation.

PMID- 19851464
TI  - Impaired control of body cooling during heterothermia represents the major
      energetic constraint in an aging non-human primate exposed to cold.
AB  - Daily heterothermia is used by small mammals for energy and water savings, and
      seems to be preferentially exhibited during winter rather than during summer.
      This feature induces a trade-off between the energy saved during daily
      heterothermia and the energy cost of arousal, which can impact energy balance and
      survival under harsh environmental conditions. Especially, aging may
      significantly affect such trade off during cold-induced energy stress, but direct
      evidences are still lacking. We hypothesized that aging could alter the
      energetics of daily heterothermia, and that the effects could differ according to
      season. In the gray mouse lemur (Microcebus murinus), a non-human primate species
      which exhibits daily heterothermia, we investigated the effects of exposures to
      25 and 12 degrees C on body composition, energy balance, patterns of
      heterothermia and water turnover in adult (N = 8) and aged animals (N = 7)
      acclimated to winter-like or summer-like photoperiods. Acclimation to summer
      prevented animals from deep heterothermia, even during aging. During winter,
      adult animals at 12 degrees C and aged animals at 25 degrees C exhibited low
      levels of energy expenditure with minor modulations of heterothermia. The major
      effects of cold were observed during winter, and were particularly pronounced in
      aged mouse lemurs which exhibited deep heterothermia phases. Body composition was
      not significantly affected by age and could not explain the age-related
      differences in heterothermia patterns. However, aging was associated with
      increased levels of energy expenditure during cold exposure, in concomitance with
      impaired energy balance. Interestingly, increased energy expenditure and depth of
      heterothermia phases were strongly correlated. In conclusion, it appeared that
      the exhibition of shallow heterothermia allowed energy savings during winter in
      adult animals only. Aged animals exhibited deep heterothermia and increased
      levels of energy expenditure, impairing energy balance. Thus, an impaired control
      of the heterothermic process induced high energy costs in the aging mouse lemur
      exposed to cold.

PMID- 19851465
TI  - An atlas of the speed of copy number changes in animal gene families and its
      implications.
AB  - The notion that gene duplications generating new genes and functions is commonly
      accepted in evolutionary biology. However, this assumption is more speculative
      from theory rather than well proven in genome-wide studies. Here, we generated an
      atlas of the rate of copy number changes (CNCs) in all the gene families of ten
      animal genomes. We grouped the gene families with similar CNC dynamics into rate
      pattern groups (RPGs) and annotated their function using a novel bottom-up
      approach. By comparing CNC rate patterns, we showed that most of the species
      specific CNC rates groups are formed by gene duplication rather than gene loss,
      and most of the changes in rates of CNCs may be the result of adaptive evolution.
      We also found that the functions of many RPGs match their biological significance
      well. Our work confirmed the role of gene duplication in generating novel
      phenotypes, and the results can serve as a guide for researchers to connect the
      phenotypic features to certain gene duplications.

PMID- 19851466
TI  - Can survival prediction be improved by merging gene expression data sets?
AB  - BACKGROUND: High-throughput gene expression profiling technologies generating a
      wealth of data, are increasingly used for characterization of tumor biopsies for
      clinical trials. By applying machine learning algorithms to such clinically
      documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as
      prediction of treatment response. However, the limited number of patients
      enrolled in a single trial study limits the power of machine learning approaches
      due to over-fitting. One could partially overcome this limitation by merging data
      from different studies. Nevertheless, such data sets differ from each other with
      regard to technical biases, patient selection criteria and follow-up treatment.
      It is therefore not clear at all whether the advantage of increased sample size
      outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we
      present a systematic study to answer this question specifically for breast cancer
      data sets. We use survival prediction based on Cox regression as an assay to
      measure the added value of merged data sets. RESULTS: Using time-dependent
      Receiver Operating Characteristic-Area Under the Curve (ROC-AUC) and hazard ratio
      as performance measures, we see in overall no significant improvement or
      deterioration of survival prediction with merged data sets as compared to
      individual data sets. This apparently was due to the fact that a few genes with
      strong prognostic power were not available on all microarray platforms and thus
      were not retained in the merged data sets. Surprisingly, we found that the
      overall best performance was achieved with a single-gene predictor consisting of
      CYB5D1. CONCLUSIONS: Merging did not deteriorate performance on average despite
      (a) The diversity of microarray platforms used. (b) The heterogeneity of patients
      cohorts. (c) The heterogeneity of breast cancer disease. (d) Substantial
      variation of time to death or relapse. (e) The reduced number of genes in the
      merged data sets. Predictors derived from the merged data sets were more robust,
      consistent and reproducible across microarray platforms. Moreover, merging data
      sets from different studies helps to better understand the biases of individual
      studies and can lead to the identification of strong survival factors like CYB5D1
      expression.

PMID- 19851467
TI  - Co-regulation of NF-kappaB and inflammasome-mediated inflammatory responses by
      myxoma virus pyrin domain-containing protein M013.
AB  - NF-kappaB and inflammasomes both play central roles in orchestrating anti
      pathogen responses by rapidly inducing a variety of early-response cytokines and
      chemokines following infection. Myxoma virus (MYXV), a pathogenic poxvirus of
      rabbits, encodes a member of the cellular pyrin domain (PYD) superfamily, called
      M013. The viral M013 protein was previously shown to bind host ASC-1 protein and
      inhibit the cellular inflammasome complex that regulates the activation and
      secretion of caspase 1-regulated cytokines such as IL-1beta and IL-18. Here, we
      report that human THP-1 monocytic cells infected with a MYXV construct deleted
      for the M013L gene (vMyxM013-KO), in stark contrast to the parental MYXV, rapidly
      induce high levels of secreted pro-inflammatory cytokines like TNF, IL-6, and MCP
      1, all of which are regulated by NF-kappaB. The induction of these NF-kappaB
      regulated cytokines following infection with vMyxM013-KO was also confirmed in
      vivo using THP-1 derived xenografts in NOD-SCID mice. vMyxM013-KO virus infection
      specifically induced the rapid phosphorylation of IKK and degradation of
      IkappaBalpha, which was followed by nuclear translocation of NF-kappaB/p65. Even
      in the absence of virus infection, transiently expressed M013 protein alone
      inhibited cellular NF-kappaB-mediated reporter gene expression and nuclear
      translocation of NF-kappaB/p65. Using protein/protein interaction analysis, we
      show that M013 protein also binds directly with cellular NF-kappaB1, suggesting a
      direct physical and functional linkage between NF-kappaB1 and ASC-1. We further
      demonstrate that inhibition of the inflammasome with a caspase-1 inhibitor did
      not prevent the induction of NF-kappaB regulated cytokines following infection
      with vMyxM013-KO virus, but did block the activation of IL-1beta. Thus, the
      poxviral M013 inhibitor exerts a dual immuno-subversive role in the simultaneous
      co-regulation of both the cellular inflammasome complex and NF-kappaB-mediated
      pro-inflammatory responses.

PMID- 19851468
TI  - Evasion by stealth: inefficient immune activation underlies poor T cell response
      and severe disease in SARS-CoV-infected mice.
AB  - Severe Acute Respiratory Syndrome caused substantial morbidity and mortality
      during the 2002-2003 epidemic. Many of the features of the human disease are
      duplicated in BALB/c mice infected with a mouse-adapted version of the virus
      (MA15), which develop respiratory disease with high morbidity and mortality.
      Here, we show that severe disease is correlated with slow kinetics of virus
      clearance and delayed activation and transit of respiratory dendritic cells (rDC)
      to the draining lymph nodes (DLN) with a consequent deficient virus-specific T
      cell response. All of these defects are corrected when mice are treated with
      liposomes containing clodronate, which deplete alveolar macrophages (AM).
      Inhibitory AMs are believed to prevent the development of immune responses to
      environmental antigens and allergic responses by interacting with lung dendritic
      cells and T cells. The inhibitory effects of AM can also be nullified if mice or
      AMs are pretreated with poly I:C, which directly activate AMs and rDCs through
      toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not
      resting bone marrow-derived dendritic cells (BMDC) protect mice from lethal MA15
      infection. These results may be relevant for SARS in humans, which is also
      characterized by prolonged virus persistence and delayed development of a SARS
      CoV-specific immune response in individuals with severe disease.

PMID- 19851469
TI  - Synthesis of phosphonate-functionalized polystyrene and poly(methyl methacrylate)
      particles and their kinetic behavior in miniemulsion polymerization.
AB  - Phosphonate-functionalized polymer nanoparticles were synthesized by free-radical
      copolymerization of vinylphosphonic acid (VPA) with styrene or methyl
      methacrylate (MMA) using the miniemulsion technique. The influence of different
      parameters such as monomer and surfactant type, amount of vinylphosphonic acid on
      the average particle size, and size distribution was studied using dynamic light
      scattering and transmission electron microscopy. Depending on the amount and type
      of the surfactant used (ionic or non-ionic), phosphonate-functionalized particles
      in a size range from 102 to 312 nm can be obtained. The density of the
      phosphonate groups on the particle surface was higher in the case of using MMA as
      a basis monomer than polystyrene. The kinetic behavior of VPA copolymerization
      with styrene or MMA using a hydrophobic initiator was investigated by reaction
      calorimetry. Different kinetic curves were observed for miniemulsion
      (co)polymerization of styrene- and MMA-based nanoparticles indicating different
      nucleation mechanisms.

PMID- 19851471
TI  - A systematic review of new advances in the management of mucopolysaccharidosis VI
      (Maroteaux-Lamy syndrome): focus on galsulfase.
AB  - INTRODUCTION: Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) is
      an autosomal recessive lysosomal storage disorder, characterized primarily by
      skeletal dysplasia and joint contracture. It is caused by a deficiency of N
      acetylgalactosamine-4-sulfatase (arylsulfatase B), for which a recombinant
      formulation (galsulfase) is available as replacement therapy. OBJECTIVE: To
      evaluate the effectiveness and safety of galsulfase compared to placebo or no
      interventions, for treating MPS VI. We also considered studies evaluating
      different doses of galsulfase. METHODS: A systematic review of the literature was
      conducted. A computerized electronic search in MEDLINE, EMBASE, CENTRAL, SciELO,
      and LILACS was carried on to identify any randomized trials that met our
      inclusion criteria. RESULTS: Two studies were included in the review. Because the
      number of studies was small, our analysis probably did not find any statistically
      significant difference. Long-term follow-up will be required to ascertain full
      clinical benefit, on both event-free survival and quality of life measures.
      CONCLUSIONS: There is some evidence to support the use of galsulfase in the
      treatment of MPS VI; however due to the very low quantity of included studies we
      could not analyze it in an appropriate way. This review highlights the need for
      continued research into the use of enzyme replacement therapy for MPS VI.

PMID- 19851470
TI  - Biological targets in the treatment of rheumatoid arthritis: a comprehensive
      review of current and in-development biological disease modifying anti-rheumatic
      drugs.
AB  - Enhanced understanding of the rheumatoid arthritis (RA) pathophysiology and the
      role of cytokines has enabled the development of innovative biological agents in
      the last 10 years that target specific parts of the immune response. Failure to
      achieve adequate response with traditional disease modifying anti-rheumatic drugs
      (DMARDs) and increasing evidence of ongoing radiographic deterioration of the
      affected joints despite seemingly clinical response were essential stimuli for
      the development of biologics. The current and upcoming biological agents are
      primarily aimed at neutralizing circulating and cell-bound pro-inflammatory
      cytokines, interfering in the interaction of antigen-presenting and T
      lymphocytes, eliminating circulating B-lymphocytes or by interfering with the
      intracellular signaling mechanisms of immuno-competent cells that lead to
      inflammation. These agents have improved the currently available treatments due
      to greater efficacy, fast action and greater tolerability. However, use of these
      agents has also been associated with significant, although rare, adverse events
      and considerable cost. Therefore, these agents should be used with caution by
      experienced clinicians. The present work aims to provide a global and updated
      review of the current and in-development biological DMARDs for the treatment of
      RA.

PMID- 19851472
TI  - Local cytokines and clinical symptoms in children with allergic rhinitis after
      different treatments.
AB  - BACKGROUND: Therapy for allergic rhinitis aims to control symptoms and improve
      the quality of life. The treatment of allergic rhinitis includes allergen
      avoidance, environmental controls, pharmacologic treatment, and specific
      immunotherapy. OBJECTIVES: The aim of this study is to evaluate the clinical
      changes and the levels of interferon-gamma (IFN-gamma) and interleukin-5 (IL-5)
      in nasal lavage fluid from children with allergic rhinitis after different types
      of pharmacologic treatment (mometasone, montelukast, or desloratadine). METHODS:
      Twenty-four children aged from six to 12 years with moderate persistent allergic
      rhinitis were randomized into three groups receiving monotherapy treatment over
      four weeks: nasal corticosteroid (mometasone), leukotriene modifier
      (montelukast), or antihistamine (desloratadine). The perception of symptom
      improvement during the medication use was evaluated at the end of the treatment.
      Samples of nasal lavage fluid were collected before and after treatment for
      measuring IFN-gamma and IL-5 cytokines by ELISA. RESULTS: All parents perceived
      an improvement in symptoms. Significant enhancement was seen in the mometasone
      group compared to those with montelukast (P = 0.01) and desloratadine (P = 0.02).
      No significant differences were found among the three groups in the levels of IL
      5 and IFN-gamma in nasal fluid at baseline or after treatment. Only the group
      treated with mometasone showed a slight but significant reduction in IL-5 levels
      after the treatment period as compared with levels before the treatment (P =
      0.0469). CONCLUSION: The group treated with mometasone showed better improvement
      of clinical symptoms and a slight reduction in IL-5 levels in the nasal fluid.
      This may indirectly reflect the relative immunomodulatory effects of the drugs
      tested.

PMID- 19851473
TI  - Foreign body aspirations in infancy: a 20-year experience.
AB  - OBJECTIVE: Foreign body aspirations comprise the majority of accidental deaths in
      childhood. Diagnostic delay may cause an increase in mortality and morbidity in
      cases without acute respiratory failure. We report our diagnostic and compare the
      relevant studies available in literature to our results. METHODS: In our
      Hospital, bronchoscopy was performed on 1015 patients with the diagnosis of
      foreign body aspirations (from 1998 to 2008). Of these cases, 63.5% were male and
      36.5% female. Their ages ranged from 2 months to 9 years (mean 2.3 years).
      Diagnosis was made on history, physical examination, radiological methods and
      bronchoscopy. RESULTS: Foreign bodies were localized in the right main bronchus
      in 560 (55.1%) patients followed by left main bronchus in 191 (18.8%), trachea in
      173 (17.1%), vocal cord in 75 (7.4%) and both bronchus in 16 (1.6%). Foreign body
      was not found during bronchoscopy in 48 cases (8.7%). The majority of the foreign
      bodies were seeds. Foreign bodies were removed with bronchoscopy in all cases.
      Pneumonia occurs in only 2.9% (29/1015) patients out of our cases. CONCLUSION:
      Rigid bronchoscopy is very effective procedure for inhaled foreign body removal
      with fewer complications. Proper use of diagnostic techniques provides a high
      degree of success, and the treatment modality to be used depending on the type of
      the foreign body is mostly satisfactory.

PMID- 19851474
TI  - Private Pediatric Clinic Characteristics Associated with Influenza Immunization
      Efforts in the State of Georgia: A Pilot Evaluation.
AB  - The Advisory Committee on Immunization Practices (ACIP) recently recommended that
      all children 6 months to 18 years be vaccinated annually against influenza.
      Because pediatricians will be critical for implementing this recommendation, we
      assessed the characteristics of immunization providers associated with the
      greatest efforts to vaccinate children against influenza. Using a cross-sectional
      survey of 35 private pediatric clinics in Georgia, we found that adding extra
      hours for immunization during the influenza vaccination season and having a
      policy of allowing six or more vaccines to be delivered at one appointment were
      characteristics associated with a greater intent to vaccinate children in the
      2004-2005 influenza vaccination season. Most respondents indicated that for their
      clinic to implement a universal childhood vaccination policy it would be
      important to have a formal recommendation from the ACIP and American Academy of
      Pediatrics, and to be assured that they could receive credits or refunds for
      unused vaccine.

PMID- 19851475
TI  - Thermodynamic properties of liquid water: an application of a nonparametric
      approach to computing the entropy of a neat fluid.
AB  - Due to its fundamental importance to molecular biology, great interest has
      continued to persist in developing novel techniques to efficiently characterize
      the thermodynamic and structural features of liquid water. A particularly
      fruitful approach, first applied to liquid water by Lazaridis and Karplus, is to
      use molecular dynamics or Monte Carlo simulations to collect the required
      statistics to integrate the inhomogeneous solvation theory equations for the
      solvation enthalpy and entropy. We here suggest several technical improvements to
      this approach, which may facilitate faster convergence and greater accuracy. In
      particular, we devise a nonparametric k'th nearest neighbors (NN) based approach
      to estimate the water-water correlation entropy, and suggest an alternative
      factorization of the water-water correlation function that appears to more
      robustly describe the correlation entropy of the neat fluid. It appears that the
      NN method offers several advantages over the more common histogram based
      approaches, including much faster convergence for a given amount of simulation
      data; an intuitive error bound that may be readily formulated without resorting
      to block averaging or bootstrapping; and the absence of empirically tuned
      parameters, which may bias the results in an uncontrolled fashion.

PMID- 19851476
TI  - Genomic instability and DNA damage responses in progeria arising from defective
      maturation of prelamin A.
AB  - Progeria syndromes have in common a premature aging phenotype and increased
      genome instability. The susceptibility to DNA damage arises from a compromised
      repair system, either in the repair proteins themselves or in the DNA damage
      response pathways. The most severe progerias stem from mutations affecting lamin
      A production, a filamentous protein of the nuclear lamina. Hutchinson-Gilford
      progeria syndrome (HGPS) patients are heterozygous for aLMNA gene mutation while
      Restrictive Dermopathy (RD) individuals have a homozygous deficiency in the
      processing protease Zmpste24. These mutations generate the mutant lamin A
      proteins progerin and FC-lamina A, respectively, which cause nuclear deformations
      and chromatin perturbations. Genome instability is observed even though genome
      maintenance and repair genes appear normal. The unresolved question is what
      features of the DNA damage response pathways are deficient in HGPS and RD cells.
      Here we review and discuss recent findings which resolve some mechanistic details
      of how the accumulation of progerin/FC-lamin A proteins may disrupt DNA damage
      response pathways in HGPS and RD cells. As the mutant lamin proteins accumulate
      they sequester replication and repair factors, leading to stalled replication
      forks which collapse into DNA double-strand beaks (DSBs). In a reaction unique to
      HGPS and RD cells these accessible DSB termini bind Xeroderma pigmentosum group A
      (XPA) protein which excludes normal binding by DNA DSB repair proteins. The bound
      XPA also signals activation of ATM and ATR, arresting cell cycle progression,
      leading to arrested growth. In addition, the effective sequestration of XPA at
      these DSB damage sites makes HGPS and RD cells more sensitive to ultraviolet
      light and other mutagens normally repaired by the nucleotide excision repair
      pathway of which XPA is a necessary and specific component.

PMID- 19851478
TI  - Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic
      Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION).
AB  - Articular cartilage exhibits viscoelasticity in response to mechanical loading
      that is well described using biphasic or poroelastic continuum models. To date,
      boundary element methods (BEMs) have not been employed in modeling biphasic
      tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the
      Laplace transform domain, is applied to modeling stress relaxation in cartilage.
      Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined
      compression is simulated and validated against a theoretical solution.
      Microscopic cell deformation due to poroelastic stress relaxation is also
      modeled. An extended Laplace inversion method is employed to accurately represent
      mechanical responses in the time domain.

PMID- 19851477
TI  - dSir2 and Dmp53 interact to mediate aspects of CR-dependent lifespan extension in
      D. melanogaster.
AB  - Calorie Restriction (CR) is a well established method of extending life span in a
      variety of organisms. In the fruit fly D. melanogaster, CR is mediated at least
      in part by activation of dSir2. In mammalian systems, one of the critical targets
      of Sir2 is the tumor suppressor p53. This deacetylation of p53 by Sir2 leads to
      inhibition of p53's transcriptional activity. We have recently shown that
      inhibition of Dmp53 activity in the fly brain through the use of dominant
      negative (DN) constructs that inhibit DNA-binding can extend life span. This life
      span extension appears to be related to CR, as CR and DN-Dmp53 donot display
      additive effects on life span. Here we report that life span extension by DN
      Dmp53 expression is highly dynamic and can be achieved even when DN-Dmp53 is
      expressed later in life. In addition, we demonstrate that life span extension by
      activation of dSir2 and DN-Dmp53 expression are not additive. Furthermore, we
      show that dSir2 physically interacts with Dmp53 and can deacetylate Dmp53-derived
      peptides. Taken together, our data demonstrate that Dmp53 is a down stream target
      of dSir2 enzymatic activity and mediates some aspects of the life span extending
      effects of CR.

PMID- 19851480
TI  - Stimulus and Response Expectancies Influence the Cognitive Effects of Cigarettes.
AB  - The pharmacological, stimulus expectancy, and response expectancy effects of
      light cigarettes (0.60 mg yield of nicotine) compared with virtually nicotine
      free cigarettes (less than 0.05 mg yield of nicotine) were examined using a
      between-subjects design. A total of 103 college-student smokers completed tests
      of cognition before and after smoking one type of cigarette, which was evaluated
      on a number of dimensions. Cigarettes with nicotine were preferred on most
      dimensions, and stimulus expectancy partially mediated the relationship between
      nicotine and subjective effects of the cigarettes. Stimulus expectancy also
      mediated the effect of nicotine on tension reduction immediately after smoking,
      but not near the end of the experiment. Response expectancy effects of nicotine
      were related to predicted and actual recall performance, such that participants
      who performed well tended to attribute the effect to the cigarette they smoked.
      Implications for smoking cessation and research studies using non-nicotine
      cigarettes are discussed.

PMID- 19851479
TI  - Integrative systems control approach for reactivating Kaposi's sarcoma-associated
      herpesvirus (KSHV) with combinatory drugs.
AB  - Cells serve as basic units of life and represent intricate biological molecular
      systems. The vast number of cellular molecules with their signaling and
      regulatory circuitries forms an intertwined network. In this network, each
      pathway interacts non-linearly with others through different intermediates. Thus,
      the challenge of manipulating cellular functions for desired outcomes, such as
      cancer eradication and controlling viral infection lies within the integrative
      system of regulatory circuitries. By using a closed-loop system control scheme,
      we can efficiently analyze biological signaling networks and manipulate their
      behavior through multiple stimulations on a collection of pathways. Specifically,
      we aimed to maximize the reactivation of Kaposi's Sarcoma-associated Herpesvirus
      (KSHV) in a Primary Effusion Lymphoma cell line. The advantage of this approach
      is that it is well-suited to study complex integrated systems; it circumvents the
      need for detailed information of individual signaling components; and it
      investigates the network as a whole by utilizing key systemic outputs as
      indicators.

PMID- 19851482
TI  - The next generation of electronic journals: prospects and problems.

PMID- 19851483
TI  - National Institutes of Health public access policy assistance: one library's
      approach.

PMID- 19851484
TI  - Questions regarding "An Analysis of Bibliometric Indicators, National Institutes
      of Health Funding, and Faculty Size at Association of American Medical Colleges
      medical schools, 1997-2007".

PMID- 19851485
TI  - PubMed growth patterns and visibility of journals of Sub-Saharan African origin.

PMID- 19851487
TI  - A case study: planning a statewide information resource for health professionals:
      an evidence-based approach.
AB  - QUESTION: What is the best approach for implementing a statewide electronic
      health library (eHL) to serve all health professionals in Minnesota? SETTING: The
      research took place at the University of Minnesota Health Sciences Libraries.
      METHODS: In January 2008, the authors began planning a statewide eHL for health
      professionals following the five-step process for evidence-based librarianship:
      formulating the question, finding the best evidence, appraising the evidence,
      assessing costs and benefits, and evaluating the effectiveness of resulting
      actions. MAIN RESULTS: The authors identified best practices for developing a
      statewide eHL for health professionals relating to audience or population served,
      information resources, technology and access, funding model, and implementation
      and sustainability. They were compared to the mission of the eHL project to drive
      strategic directions by developing recommendations. CONCLUSION: EBL can guide the
      planning process for a statewide eHL, but findings must be tailored to the local
      environment to address information needs and ensure long-term sustainability.

PMID- 19851488
TI  - Teaching Web 2.0 technologies using Web 2.0 technologies.
AB  - OBJECTIVES: The research evaluated participant satisfaction with the content and
      format of the "Web 2.0 101: Introduction to Second Generation Web Tools" course
      and measured the impact of the course on participants' self-evaluated knowledge
      of Web 2.0 tools. METHODS: The "Web 2.0 101" online course was based loosely on
      the Learning 2.0 model. Content was provided through a course blog and covered a
      wide range of Web 2.0 tools. All Medical Library Association members were invited
      to participate. Participants were asked to complete a post-course survey.
      Respondents who completed the entire course or who completed part of the course
      self-evaluated their knowledge of nine social software tools and concepts prior
      to and after the course using a Likert scale. Additional qualitative information
      about course strengths and weaknesses was also gathered. RESULTS: Respondents'
      self-ratings showed a significant change in perceived knowledge for each tool,
      using a matched pair Wilcoxon signed rank analysis (P<0.0001 for each
      tool/concept). Overall satisfaction with the course appeared high. Hands-on
      exercises were the most frequently identified strength of the course; the length
      and time-consuming nature of the course were considered weaknesses by some.
      CONCLUSION: Learning 2.0-style courses, though demanding time and self-motivation
      from participants, can increase knowledge of Web 2.0 tools.

PMID- 19851489
TI  - Content analysis of cancer blog posts.
AB  - OBJECTIVES: The efficacy of user-defined subject tagging and software-generated
      subject tagging for describing and organizing cancer blog contents was explored.
      METHODS: The Technorati search engine was used to search the blogosphere for
      cancer blog postings generated during a two-month period. Postings were mined for
      relevant subject concepts, and blogger-defined tags and Text Analysis Portal for
      Research (TAPoR) software-defined tags were generated for each message.
      Descriptive data were collected, and the blogger-defined tags were compared with
      software-generated tags. Three standard vocabularies (Opinion Templates, Basic
      Resource, and Medical Subject Headings [MeSH] Resource) were used to assign
      subject terms to the blogs, with results compared for efficacy in information
      retrieval. RESULTS: Descriptive data showed that most of the studied cancer blogs
      (80%) contained fewer than 500 words each. The numbers of blogger-defined tags
      per posting (M = 4.49 per posting) were significantly smaller than the TAPoR
      keywords (M = 23.55 per posting). Both blogger-defined subject tags and software
      generated subject tags were often overly broad or overly narrow in focus,
      producing less than effective search results for those seeking to extract
      information from cancer blogs. CONCLUSIONS: Additional exploration into methods
      for systematically organizing cancer blog postings is necessary if blogs are to
      become stable and efficacious information resources for cancer patients, friends,
      families, or providers.

PMID- 19851490
TI  - A pathway for hospital librarians: why is it vital?
AB  - OBJECTIVES: By the mid 2000s, reports of hospital librarians losing jobs and
      hospital libraries closing were rife. In 2005, Vital Pathways: The Hospital
      Libraries Project was established by 2005/06 MLA President M.J. Tooey, AHIP,
      FMLA, to assess the truth of these reports and to study and develop strategies to
      support hospital librarians. Throughout this long-term project, opportunities
      were sought to understand the issues more clearly. METHODS: A steering committee,
      along with three task forces, was established to carry out the work of the
      project. The steering committee provided oversight and had responsibility for
      promoting and marketing the project. The three task forces were responsible for
      conducting a survey on the status of hospital librarians, determining the
      involvement of librarians in medical education and accreditation, and researching
      and writing a document reviewing current and future roles for hospital
      librarians. Along the way, these responsibilities grew and evolved. RESULTS:
      After a little more than three years, the Task Force on Vital Pathways for
      Hospital Librarians Steering Committee presented a final report regarding its
      accomplishments to the MLA Board of Directors. A sampling of these
      accomplishments includes the status of hospital librarians survey, a website, a
      position document with an accompanying executive summary, a short promotional
      brochure, and a final culminating activity, this symposium. CONCLUSIONS: Although
      these are difficult times for all libraries, hospital librarians and libraries
      seem particularly affected. In a competitive health care environment that is
      driven by the bottom line, influenced by real estate hunger, and affected by the
      belief of hospital administrators that access to health information comes from
      the Internet and is free, the hospital librarian seems doomed. However, even in
      these difficult times, there are hospital librarians who are not only surviving,
      but thriving. Is it because they are entrepreneurial? Opportunistic? Innovative?
      Flexible? All of the above? None of the above? There are no clear predictors of
      success or of failure. However, the Vital Pathways Project has shed light on some
      of the issues and identified opportunities and strategies for the future.

PMID- 19851491
TI  - Trends in hospital librarianship and hospital library services: 1989 to 2006.
AB  - OBJECTIVE: The research studied the status of hospital librarians and library
      services to better inform the Medical Library Association's advocacy activities.
      METHODS: The Vital Pathways Survey Subcommittee of the Task Force on Vital
      Pathways for Hospital Librarians distributed a web-based survey to hospital
      librarians and academic health sciences library directors. The survey results
      were compared to data collected in a 1989 survey of hospital libraries by the
      American Hospital Association in order to identify any trends in hospital
      libraries, roles of librarians, and library services. A web-based hospital
      library report form based on the survey questions was also developed to more
      quickly identify changes in the status of hospital libraries on an ongoing basis.
      RESULTS: The greatest change in library services between 1989 and 2005/06 was in
      the area of access to information, with 40% more of the respondents providing
      access to commercial online services, 100% more providing access to Internet
      resources, and 28% more providing training in database searching and use of
      information resources. Twenty-nine percent (n = 587) of the 2005/06 respondents
      reported a decrease in staff over the last 5 years. CONCLUSIONS: Survey data
      support reported trends of consolidation of hospitals and hospital libraries and
      additions of new services. These services have likely required librarians to
      acquire new skills. It is hoped that future surveys will be undertaken to
      continue to study these trends.

PMID- 19851492
TI  - The health sciences librarian in medical education: a vital pathways project task
      force.
AB  - OBJECTIVES: The Medical Education Task Force of the Task Force on Vital Pathways
      for Hospital Librarians reviewed current and future roles of health sciences
      librarians in medical education at the graduate and undergraduate levels and
      worked with national organizations to integrate library services, education, and
      staff into the requirements for training medical students and residents. METHODS:
      Standards for medical education accreditation programs were studied, and a
      literature search was conducted on the topic of the role of the health sciences
      librarian in medical education. RESULTS: Expectations for library and information
      services in current standards were documented, and a draft standard prepared. A
      comprehensive bibliography on the role of the health sciences librarian in
      medical education was completed, and an analysis of the services provided by
      health sciences librarians was created. CONCLUSION: An essential role and
      responsibility of the health sciences librarian will be to provide the health
      care professional with the skills needed to access, manage, and use library and
      information resources effectively. Validation and recognition of the health
      sciences librarian's contributions to medical education by accrediting agencies
      will be critical. The opportunity lies in health sciences librarians embracing
      the diverse roles that can be served in this vital activity, regardless of
      accrediting agency mandates.

PMID- 19851493
TI  - Vital pathways for hospital librarians: present and future roles.
AB  - OBJECTIVES: The research objectives were to (1) describe the current and future
      roles of hospital librarians and the challenges they face and (2) find evidence
      supporting the hypothesis that librarians are essential to hospitals in achieving
      the organizations' mission-critical goals. METHOD: The authors used results from
      a previous research study that identified the five organizational mission
      critical goals important to hospital administrators and then searched the
      literature and solicited examples from hospital librarians to describe the
      librarian's role in helping hospitals achieve these goals. RESULTS: The
      literature supports the hypothesis that hospital librarians play important roles
      in the success of the hospital. Librarians support quality clinical care,
      efficient and effective hospital operations, continuing education for staff,
      research and innovation, and patient, family, and community health information
      needs. CONCLUSION: Hospital librarians fulfill many mission-critical roles in
      today's hospital, providing the right information at the right time in a variety
      of ways to enhance hospital and medical staff effectiveness, optimize patient
      care, improve patient outcomes, and increase patient and family satisfaction with
      the hospital and its services. Because hospital librarians and their services
      provide an excellent return on investment for the hospital and help the hospital
      keep its competitive edge, hospital staff should have access to the services of a
      professional librarian.

PMID- 19851494
TI  - The health information literacy research project.
AB  - OBJECTIVES: This research studied hospital administrators' and hospital-based
      health care providers' (collectively, the target group) perceived value of
      consumer health information resources and of librarians' roles in promoting
      health information literacy in their institutions. METHODS: A web-based needs
      survey was developed and administered to hospital administrators and health care
      providers. Multiple health information literacy curricula were developed. One was
      pilot-tested by nine hospital libraries in the United States and Canada.
      Quantitative and qualitative methods were used to evaluate the curriculum and its
      impact on the target group. RESULTS: A majority of survey respondents believed
      that providing consumer health information resources was critically important to
      fulfilling their institutions' missions and that their hospitals could improve
      health information literacy by increasing awareness of its impact on patient care
      and by training staff to become more knowledgeable about health literacy
      barriers. The study showed that a librarian-taught health information literacy
      curriculum did raise awareness about the issue among the target group and
      increased both the use of National Library of Medicine consumer health resources
      and referrals to librarians for health information literacy support. CONCLUSIONS:
      It is hoped that many hospital administrators and health care providers will take
      the health information literacy curricula and recognize that librarians can
      educate about the topic and that providers will use related consumer health
      services and resources.

PMID- 19851495
TI  - The Magnet journey: opportunities for librarians to partner with nurses.

PMID- 19851496
TI  - Measuring the value and impact of health sciences libraries: planning an update
      and replication of the Rochester Study.

PMID- 19851497
TI  - Comparison of journal title coverage between CINAHL and Scopus.

PMID- 19851498
TI  - Side-by-side, but from different worlds: service and resource provision by
      academic health sciences libraries to their affiliated hospitals.

PMID- 19851499
TI  - Contribution of the LIM domain and nebulin-repeats to the interaction of Lasp-2
      with actin filaments and focal adhesions.
AB  - Lasp-2 binds to actin filaments and concentrates in the actin bundles of
      filopodia and lamellipodia in neural cells and focal adhesions in fibroblastic
      cells. Lasp-2 has three structural regions: a LIM domain, a nebulin-repeat
      region, and an SH3 domain; however, the region(s) responsible for its
      interactions with actin filaments and focal adhesions are still unclear. In this
      study, we revealed that the N-terminal fragment from the LIM domain to the first
      nebulin-repeat module (LIM-n1) retained actin-binding activity and showed a
      similar subcellular localization to full-length lasp-2 in neural cells. The LIM
      domain fragment did not interact with actin filaments or localize to actin
      filament bundles. In contrast, LIM-n1 showed a clear subcellular localization to
      filopodial actin bundles. Although truncation of the LIM domain caused the loss
      of F-actin binding activity and the accumulation of filopodial actin bundles,
      these truncated fragments localized to focal adhesions. These results suggest
      that lasp-2 interactions with actin filaments are mediated through the
      cooperation of the LIM domain and the first nebulin-repeat module in vitro and in
      vivo. Actin filament binding activity may be a major contributor to the
      subcellular localization of lasp-2 to filopodia but is not crucial for lasp-2
      recruitment to focal adhesions.

PMID- 19851500
TI  - Molecular characterization of a novel Staphylococcus aureus surface protein
      (SasC) involved in cell aggregation and biofilm accumulation.
AB  - BACKGROUND: Staphylococci belong to the most important pathogens causing implant
      associated infections. Colonization of the implanted medical devices by the
      formation of a three-dimensional structure made of bacteria and host material
      called biofilm is considered the most critical factor in these infections. To
      form a biofilm, bacteria first attach to the surface of the medical device, and
      then proliferate and accumulate into multilayered cell clusters. Biofilm
      accumulation may be mediated by polysaccharide and protein factors.
      METHODOLOGY/PRINCIPAL FINDINGS: The information on Staphylococcus aureus protein
      factors involved in biofilm accumulation is limited, therefore, we searched the
      S. aureus Col genome for LPXTG-motif containing potential surface proteins and
      chose the so far uncharacterized S. aureus surface protein C (SasC) for further
      investigation. The deduced SasC sequence consists of 2186 amino acids with a
      molecular mass of 238 kDa and has features typical of gram-positive surface
      proteins, such as an N-terminal signal peptide, a C-terminal LPXTG cell wall
      anchorage motif, and a repeat region consisting of 17 repeats similar to the
      domain of unknown function 1542 (DUF1542). We heterologously expressed sasC in
      Staphylococcus carnosus, which led to the formation of huge cell aggregates
      indicative of intercellular adhesion and biofilm accumulation. To localize the
      domain conferring cell aggregation, we expressed two subclones of sasC encoding
      either the N-terminal domain including a motif that is found in various
      architectures (FIVAR) or 8 of the DUF1542 repeats. SasC or its N-terminal domain,
      but not the DUF1542 repeat region conferred production of huge cell aggregates,
      higher attachment to polystyrene, and enhanced biofilm formation to S. carnosus
      and S. aureus. SasC does not mediate binding to fibrinogen, thrombospondin-1, von
      Willebrand factor, or platelets as determined by flow cytometry.
      CONCLUSIONS/SIGNIFICANCE: Thus, SasC represents a novel S. aureus protein factor
      involved in cell aggregation and biofilm formation, which may play an important
      role in colonization during infection with this important pathogen.

PMID- 19851501
TI  - Twist: a regulator of epithelial-mesenchymal transition in lung fibrosis.
AB  - BACKGROUND: Several studies have implicated viral infection as an important
      factor in the pathogenesis of IPF and related fibrotic lung disorders. Viruses
      are thought to cause epithelial cell injury and promote epithelial-mesenchymal
      transition (EMT), a process whereby differentiated epithelial cells undergo
      transition to a mesenchymal phenotype, and considered a source of fibroblasts in
      the setting of lung injury. We have demonstrated an association between the
      epithelial injury caused by chronic herpes virus infection with the murine gamma
      herpes virus, MHV68, and lung fibrosis. We hypothesize that EMT in this model of
      virus-induced pulmonary fibrosis is driven by the expression of the transcription
      factor Twist. METHODS/FINDINGS: In vitro MHV68 infection of murine lung
      epithelial cells induced expression of Twist, and mesenchymal markers. Stable
      overexpression of Twist promoted EMT in MLE15 lung epithelial cells. Transient
      knockdown expression of Twist resulted in preservation of epithelial phenotype
      after in vitro MHV68 infection. In concordance, high expression of Twist was
      found in lung epithelial cells of MHV68 infected mice, but not in mock infected
      mice. Alveolar epithelial cells from lung tissue of idiopathic pulmonary fibrosis
      (IPF) patients were strongly positive for Twist. These cells demonstrated
      features of EMT with low expression of E-cadherin and upregulation of the
      mesenchymal marker N-cadherin. Finally, IPF tissue with high Twist protein levels
      was also positive for the herpesvirus, EBV. CONCLUSIONS/SIGNIFICANCE: We conclude
      that Twist contributes to EMT in the model of virus-induced pulmonary fibrosis.
      We speculate that in some IPF cases, gamma-herpes virus infection with EBV might
      be a source of injury precipitating EMT through the expression of Twist.

PMID- 19851502
TI  - Identification, RNAi knockdown, and functional analysis of an ejaculate protein
      that mediates a postmating, prezygotic phenotype in a cricket.
AB  - Postmating, prezygotic phenotypes, especially those that underlie reproductive
      isolation between closely related species, have been a central focus of
      evolutionary biologists over the past two decades. Such phenotypes are thought to
      evolve rapidly and be nearly ubiquitous among sexually reproducing eukaryotes
      where females mate with multiple partners. Because these phenotypes represent
      interplay between the male ejaculate and female reproductive tract, they are
      fertile ground for reproductive senescence--as ejaculate composition and female
      physiology typically change over an individual's life span. Although these
      phenotypes and their resulting dynamics are important, we have little
      understanding of the proteins that mediate these phenotypes, particularly for
      species groups where postmating, prezygotic traits are the primary mechanism of
      reproductive isolation. Here, we utilize proteomics, RNAi, mating experiments,
      and the Allonemobius socius complex of crickets, whose members are primarily
      isolated from one another by postmating, prezygotic phenotypes (including the
      ability of a male to induce a female to lay eggs), to demonstrate that one of the
      most abundant ejaculate proteins (a male accessory gland-biased protein similar
      to a trypsin-like serine protease) decreases in abundance over a male's
      reproductive lifetime and mediates the induction of egg-laying in females. These
      findings represent one of the first studies to identify a protein that plays a
      role in mediating both a postmating, prezygotic isolation pathway and
      reproductive senescence.

PMID- 19851503
TI  - The endo-siRNA pathway is essential for robust development of the Drosophila
      embryo.
AB  - BACKGROUND: Robustness to natural temperature fluctuations is critical to proper
      development in embryos and to cellular functions in adult organisms. However,
      mechanisms and pathways which govern temperature compensation remain largely
      unknown beyond circadian rhythms. Pathways which ensure robustness against
      temperature fluctuations may appear to be nonessential under favorable, uniform
      environmental conditions used in conventional laboratory experiments where there
      is little variation for which to compensate. The endo-siRNA pathway, which
      produces small double-stranded RNAs in Drosophila, appears to be nonessential for
      robust development of the embryo under ambient uniform temperature and to be
      necessary only for viral defense. Embryos lacking a functional endo-siRNA pathway
      develop into phenotypically normal adults. However, we hypothesized that small
      RNAs may regulate the embryo's response to temperature, as a ribonucleoprotein
      complex has been previously shown to mediate mammalian cell response to heat
      shock. PRINCIPAL FINDINGS: Here, we show that the genes DICER-2 and ARGONAUTE2,
      which code for integral protein components of the endo-siRNA pathway, are
      essential for robust development and temperature compensation in the Drosophila
      embryo when exposed to temperature perturbations. The regulatory functions of
      DICER-2 and ARGONAUTE2 were uncovered by using microfluidics to expose developing
      Drosophila embryos to a temperature step, in which each half of the embryo
      develops at a different temperature through developmental cycle 14. Under this
      temperature perturbation, dicer-2 or argonaute2 embryos displayed abnormal
      segmentation. The abnormalities in segmentation are presumably due to the
      inability of the embryo to compensate for temperature-induced differences in rate
      of development and to coordinate developmental timing in the anterior and
      posterior halves. A deregulation of the length of nuclear division cycles 10-14
      is also observed in dicer-2 embryos at high temperatures. CONCLUSIONS: Results
      presented herein uncover a novel function of the endo-siRNA pathway in
      temperature compensation and cell cycle regulation, and we hypothesize that the
      endo-siRNA pathway may regulate the degradation of maternal cell cycle
      regulators. Endo-siRNAs may have a more general role buffering against
      environmental perturbations in other organisms.

PMID- 19851504
TI  - Infectivity of Leishmania mexicana is associated with differential expression of
      protein kinase C-like triggered during a cell-cell contact.
AB  - Mammalian host cell invasion by Leishmania is a complex process in which various
      parasite and host cell components interact, triggering the activation of
      signaling cascades in both cells. Little is known regarding PKC biological
      functions in Leishmania sp. during parasite-macrophage interaction. PKC-like
      enzyme was first identified in homogenates and membrane fraction of L. mexicana
      stationary promastigotes by immunoblot. PKC-like enzyme activity was then
      detected in cell homogenates but also on intact promastigotes showing for the
      first time the presence of an ecto-PKC dependent on Ca(2+)/phosphatidylserine for
      activation. This ecto-PKC was activated with phorbol myristate acetate (PMA) and
      inhibited by RO-32-0432, a selective PKCalphabeta(I)epsilon bisindolylmaleimide
      inhibitor. Interestingly, the Leishmania PKC- activity was higher in the
      infective stationary than in non-infective logarithmic stage. Then, promastigotes
      at different stages of time proliferation curve were used in order to identify
      the role of PKC-like during macrophage invasion. After attachment to macrophages,
      PKC-like is over-expressed in promastigotes at the 6(th) culture day but also at
      the 4(th) day of culture corresponding to the maximal infection capacity. An
      antibody microarray for MAPK and PKC corroborate the Leishmania PKC-like over
      expression during contact with macrophages. Pretreatment with RO-32-0432
      inhibitor reduced the number of infected macrophages and the parasite burden.
      These data suggest for the first time a direct link between PKC expression level
      and infectivity, and provide evidence that PKC-like plays a critical role in
      attachment and in the internalization steps involved in the invasion process.

PMID- 19851505
TI  - Isolation of cell nuclei using inert macromolecules to mimic the crowded
      cytoplasm.
AB  - Cell nuclei are commonly isolated and studied in media which include millimolar
      concentrations of cations, which conserve the nuclear volume by screening the
      negative charges on chromatin and maintaining its compaction. However, two
      factors question if these ionic conditions correctly reproduce the environment of
      nuclei in vivo: the small-scale motion and conformation of chromatin in vivo are
      not reproduced in isolated nuclei, and experiments and theory suggest that small
      ions in the cytoplasm are not free in the soluble phase but are predominantly
      bound to macromolecules. We studied the possible role in maintaining the
      structure and functions of nuclei in vivo of a further but frequently overlooked
      property of the cytoplasm, the crowding or osmotic effects caused by diffusible
      macromolecules whose concentration, measured in several studies, is in the range
      of 130 mg/ml. Nuclei which conserved their volume in the cell and their
      ultrastructure seen by electron microscopy were released from K562 cells in media
      containing the inert polymer 70 kDa Ficoll (50% w/v) or 70 kDa dextran (35% w/v)
      to replace the diffusible cytoplasmic molecules which were dispersed on cell
      lysis with digitonin, with 100 microM K-Hepes buffer as the only source of ions.
      Immunofluorescence labelling and experiments using cells expressing GFP-fusion
      proteins showed that internal compartments (nucleoli, PML and coiled bodies, foci
      of RNA polymerase II) were conserved in these nuclei, and nascent RNA transcripts
      could be elongated. Our observations are consistent with the hypothesis that
      crowding by diffusible cytoplasmic macromolecules is a crucial but overlooked
      factor which supports the nucleus in vivo by equilibrating the opposing osmotic
      pressure cause by the high concentration of macromolecules in the nucleus, and
      suggest that crowded media provide more physiological conditions to study nuclear
      structure and functions. They may also help to resolve the long-standing paradox
      that the small-scale motion and irregular conformation of chromatin seen in vivo
      are not reproduced in nuclei isolated in conventional ionic media.

PMID- 19851506
TI  - The nuclear protein Sge1 of Fusarium oxysporum is required for parasitic growth.
AB  - Dimorphism or morphogenic conversion is exploited by several pathogenic fungi and
      is required for tissue invasion and/or survival in the host. We have identified a
      homolog of a master regulator of this morphological switch in the plant
      pathogenic fungus Fusarium oxysporum f. sp. lycopersici. This non-dimorphic
      fungus causes vascular wilt disease in tomato by penetrating the plant roots and
      colonizing the vascular tissue. Gene knock-out and complementation studies
      established that the gene for this putative regulator, SGE1 (SIX Gene Expression
      1), is essential for pathogenicity. In addition, microscopic analysis using
      fluorescent proteins revealed that Sge1 is localized in the nucleus, is not
      required for root colonization and penetration, but is required for parasitic
      growth. Furthermore, Sge1 is required for expression of genes encoding effectors
      that are secreted during infection. We propose that Sge1 is required in F.
      oxysporum and other non-dimorphic (plant) pathogenic fungi for parasitic growth.

PMID- 19851507
TI  - Molecular and sensory basis of a food related two-state behavior in C. elegans.
AB  - Most animals display multiple behavioral states and control the time allocation
      to each of their activity phases depending on their environment. Here we develop
      a new quantitative method to analyze Caenorhabditis elegans behavioral states. We
      show that the dwelling and roaming two-state behavior of C. elegans is tightly
      controlled by the concentration of food in the environment of the animal. Sensory
      perception through the amphid neurons is necessary to extend roaming phases while
      internal metabolic perception of food nutritional value is needed to induce
      dwelling. Our analysis also shows that the proportion of time spent in each state
      is modulated by past nutritional experiences of the animal. This two-state
      behavior is regulated through serotonin as well as insulin and TGF-beta signaling
      pathways. We propose a model where food nutritional value is assessed through
      internal metabolic signaling. Biogenic amines signaling could allow the worm to
      adapt to fast changes in the environment when peptide transcriptional pathways
      may mediate slower adaptive changes.

PMID- 19851508
TI  - A computational predictor of human episodic memory based on a theta phase
      precession network.
AB  - In the rodent hippocampus, a phase precession phenomena of place cell firing with
      the local field potential (LFP) theta is called "theta phase precession" and is
      considered to contribute to memory formation with spike time dependent plasticity
      (STDP). On the other hand, in the primate hippocampus, the existence of theta
      phase precession is unclear. Our computational studies have demonstrated that
      theta phase precession dynamics could contribute to primate-hippocampal dependent
      memory formation, such as object-place association memory. In this paper, we
      evaluate human theta phase precession by using a theory-experiment combined
      analysis. Human memory recall of object-place associations was analyzed by an
      individual hippocampal network simulated by theta phase precession dynamics of
      human eye movement and EEG data during memory encoding. It was found that the
      computational recall of the resultant network is significantly correlated with
      human memory recall performance, while other computational predictors without
      theta phase precession are not significantly correlated with subsequent memory
      recall. Moreover the correlation is larger than the correlation between human
      recall and traditional experimental predictors. These results indicate that theta
      phase precession dynamics are necessary for the better prediction of human recall
      performance with eye movement and EEG data. In this analysis, theta phase
      precession dynamics appear useful for the extraction of memory-dependent
      components from the spatio-temporal pattern of eye movement and EEG data as an
      associative network. Theta phase precession may be a common neural dynamic
      between rodents and humans for the formation of environmental memories.

PMID- 19851509
TI  - Endoribonuclease L (RNase L) regulates the myogenic and adipogenic potential of
      myogenic cells.
AB  - Skeletal muscle maintenance and repair involve several finely coordinated steps
      in which pluripotent stem cells are activated, proliferate, exit the cell cycle
      and differentiate. This process is accompanied by activation of hundreds of
      muscle-specific genes and repression of genes associated with cell proliferation
      or pluripotency. Mechanisms controlling myogenesis are precisely coordinated and
      regulated in time to allow the sequence of activation/inactivation of genes
      expression. Muscular differentiation is the result of the interplay between
      several processes such as transcriptional induction, transcriptional repression
      and mRNA stability. mRNA stability is now recognized as an essential mechanism of
      control of gene expression. For instance, we previously showed that the
      endoribonuclease L (RNase L) and its inhibitor (RLI) regulates MyoD mRNA
      stability and consequently muscle differentiation.We now performed global gene
      expression analysis by SAGE to identify genes that were down-regulated upon
      activation of RNase L in C2C12 myogenic cells, a model of satellite cells. We
      found that RNase L regulates mRNA stability of factors implicated in the control
      of pluripotency and cell differentiation. Moreover, inappropriate RNase L
      expression in C2C12 cells led to inhibition of myogenesis and differentiation
      into adipocytes even when cells were grown in conditions permissive for muscle
      differentiation. Conversely, over-expression of RLI allowed muscle
      differentiation of myogenic C2C12 cells even in non permissive conditions.These
      findings reveal the central role of RNase L and RLI in controlling gene
      expression and cell fate during myogenesis. Our data should provide valuable
      insights into the mechanisms that control muscle stem cell differentiation and
      into the mechanism of metaplasia observed in aging or muscular dystrophy where
      adipose infiltration of muscle occurs.

PMID- 19851510
TI  - Critical role of activating transcription factor 4 in the anabolic actions of
      parathyroid hormone in bone.
AB  - Parathyroid hormone (PTH) is a potent anabolic agent for the treatment of
      osteoporosis. However, its mechanism of action in osteoblast and bone is not well
      understood. In this study, we show that the anabolic actions of PTH in bone are
      severely impaired in both growing and adult ovariectomized mice lacking bone
      related activating transcription factor 4 (ATF4). Our study demonstrates that
      ATF4 deficiency suppresses PTH-stimulated osteoblast proliferation and survival
      and abolishes PTH-induced osteoblast differentiation, which, together, compromise
      the anabolic response. We further demonstrate that the PTH-dependent increase in
      osteoblast differentiation is correlated with ATF4-dependent up-regulation of
      Osterix. This regulation involves interactions of ATF4 with a specific enhancer
      sequence in the Osterix promoter. Furthermore, actions of PTH on Osterix require
      this same element and are associated with increased binding of ATF4 to chromatin.
      Taken together these experiments establish a fundamental role for ATF4 in the
      anabolic actions of PTH on the skeleton.

PMID- 19851511
TI  - Gastrointestinal tolerability with ibandronate after previous weekly
      bisphosphonate treatment.
AB  - Data from two open-label trials (PRIOR and CURRENT) of women with postmenopausal
      osteoporosis or osteopenia were evaluated to assess whether monthly oral and
      quarterly intravenous (IV) ibandronate dosing improved self-reported
      gastrointestinal (GI) tolerability for patients who had previously experienced GI
      irritation with bisphosphonate (BP) use. In PRIOR, women who had discontinued
      daily or weekly BP treatment due to GI intolerance received monthly oral or
      quarterly IV ibandronate for 12 months. The CURRENT subanalysis included women
      receiving weekly BP treatment who switched to monthly oral ibandronate for six
      months. GI symptom severity and frequency were assessed using the Osteoporosis
      Patient Satisfaction Questionnaire. In PRIOR, mean GI tolerability scores
      increased significantly at month 1 from screening for both treatment groups
      (oral: 79.3 versus 54.1; IV: 84.4 versus 51.0; p < 0.001 for both). Most patients
      reported improvement in GI symptom severity and frequency from baseline at all
      post-screening assessments (>90% at Month 10). In the CURRENT subanalysis >60% of
      patients reported improvements in heartburn or acid reflux and >70% indicated
      improvement in other stomach upset at month 6. Postmenopausal women with GI
      irritability with daily or weekly BPs experienced improvement in symptoms with
      extended dosing monthly or quarterly ibandronate compared with baseline.

PMID- 19851512
TI  - Memantine: a review of studies into its safety and efficacy in treating
      Alzheimer's disease and other dementias.
AB  - Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist with
      moderate affinity. Its mechanism of action is neuroprotective and potentially
      therapeutic in several neuropsychiatric diseases. It has been approved by the FDA
      for the treatment of moderate to severe Alzheimer's disease (AD) either as a
      monotherapy or in combination with cholinesterase inhibitors. This review covers
      key studies of memantine's safety and efficacy in treating moderate to severe AD.
      It also covers current research into other dementias including but not
      exclusively mild AD and vascular dementia. Other studies on the efficacy of
      memantine for other neuropsychiatric diseases are discussed. Memantine is a safe
      and effective drug that merits further research on several topics. Clinicians
      should be aware of new studies and potential uses of memantine because of its
      safety and efficacy.

PMID- 19851513
TI  - Management of hypertension in the elderly patient.
AB  - Hypertension in the elderly is associated with increased occurrence rates of
      sodium sensitivity, isolated systolic hypertension, and 'white coat effect'.
      Arterial stiffness and endothelial dysfunction also increase with age. These
      factors should be considered in selecting antihypertensive therapy. The prime
      objective of this therapy is to prevent stroke. The findings of controlled trials
      show that there should be no cut-off age for treatment. A holistic program for
      controlling cardiovascular risks should be fully discussed with the patient,
      including evaluation to exclude underlying causes of secondary hypertension, and
      implementation of lifestyle measures. The choice of antihypertensive drug therapy
      is influenced by concomitant disease and previous medication history, but will
      typically include a thiazide diuretic as the first-line agent; to this will be
      added an angiotensin inhibitor and/or a calcium channel blocker. Beta blockers
      are not generally recommended, in part because they do not combat the effects of
      increased arterial stiffness. The hypertension-hypotension syndrome requires case
      specific management. Drug-resistant hypertension is important to differentiate
      from faulty compliance with medication. Patients resistant to third-line drug
      therapy may benefit from treatment with extended-release isosorbide mononitrate.
      A trial of spironolactone may also be worthwhile.

PMID- 19851514
TI  - Clinical, radiological, and biochemical characteristics in patients with diseases
      mimicking polymyalgia rheumatica.
AB  - To find out clues to differentiate between polymyalgia rheumatica (PMR) and other
      diseases that mimic PMR. We studied Japanese patients with PMR (n = 7),
      pseudogout (n = 1), remitting seronegative symmetrical synovitis with pitting
      edema (RS3PE) syndrome (n = 1), and post-infectious polyarthritis (n = 1). The
      distribution of inflammation in patients was evaluated using a gallium-67
      scintigraphy. We measured serum C-reactive protein (CRP), matrix
      metalloproteinase-3 (MMP-3), and vascular endothelial growth factor (VEGF) in
      patients before and after treatment. Further, we compared the clinical course of
      PMR with that of other diseases that mimic PMR. Patients with pseudogout, RS3PE
      syndrome, post-infectious polyarthritis manifested similar changes in
      scintigraphic findings and serum CRP, MMP-3, and VEGF levels to PMR before the
      treatment. A significant reduction in serum CRP levels at one week after use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) is a good clue to differentiate
      pseudogout and post-infectious polyarthritis from PMR. Chondrocalcinosis in the
      radiographs of joints is also effective to differentiate pseudogout from PMR. A
      small reduction of CRP levels after NSAIDs use and promptly ameliorated CRP and
      symptoms by a low-dose steroid therapy, which was commonly observed in patients
      with PMR, were also found in a patient with RS3PE syndrome. Pitting edema of the
      back of hands and gallium uptake in metacarpophalangeal (MCP) joints were useful
      to differentiate RS3PE syndrome from PMR. In conclusion, pseudogout, RS3PE
      syndrome, post-infectious polyarthritis should be included in the spectrum of
      diseases mimicking PMR. A promptly decreased serum CRP level by NSAIDs is a good
      clue to differentiate pseudogout and post-infectious polyarthritis from PMR.
      Pitting edema of the back of hands and symmetric gallium uptake in MCP joints are
      characteristic for RS3PE syndrome.

PMID- 19851515
TI  - Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I
      disorder.
AB  - Asenapine is a new atypical antipsychotic agent currently under development for
      the treatment of schizophrenia and bipolar disorder. It has high affinity for
      various receptors including antagonism at 5HT(2A), 5HT(2B), 5HT(2C), 5HT(6) and
      5HT(7) serotonergic receptor subtypes, alpha(1A), alpha(2A), alpha(2B) and
      alpha(2C) adrenergic and D(3) and D(4) dopaminergic receptors. As with other
      atypicals, asenapine exhibits a high 5HT(2A):D(2) affinity ratio. Although
      similar to clozapine in its multi-target profile, it shows no appreciable
      affinity for muscarinic receptors. Asenapine has shown efficacy in alleviating
      both positive and negative symptoms of schizophrenia compared with placebo.
      Although promising, further studies are required in order to determine whether it
      has advantages over placebo and other antipsychotics in alleviating cognitive
      impairment associated with schizophrenia. It has also shown long-term efficacy
      comparable with olanzapine in bipolar I disorder. Asenapine is generally well
      tolerated and appears to be metabolically neutral. It has low propensity to cause
      weight gain and prolactin elevation. There were no concerns in the studies about
      its effects on the cardiovascular system and QTc prolongation. The incidence of
      extrapyramidal symptoms with asenapine however has been found to be higher than
      that with olanzapine. It may be a useful alternative to aripiprazole in
      schizophrenia and bipolar disorder in patients who are at high risk of metabolic
      abnormalities.

PMID- 19851516
TI  - Measurement of treatment adherence with antipsychotic agents in patients with
      schizophrenia.
AB  - The importance of medication adherence in sustaining control of schizophrenic
      symptoms has generated a great deal of interest in comparing levels of treatment
      adherence with different antipsychotic agents. However, the bulk of the research
      has yielded results that are often inconsistent. In this prospective,
      observational study, we assessed the measurement properties of 3 commonly used,
      pharmacy-based measures of treatment adherence with antipsychotic agents in
      schizophrenia using data from the Veterans Health Administration during 2000 to
      2005. Patients were selected if they were on antipsychotics and diagnosed with
      schizophrenia (N = 18,425). A gap of >/=30 days (with no filled index medication)
      was used to define discontinuation of treatment as well as medication "episodes,"
      or the number of times a patient returned to the same index agent after
      discontinuation of treatment within a 1-year period. The study found that the 3
      existing measures differed in their approaches in measuring treatment adherence,
      suggesting that studies using these different measures would generate different
      levels of treatment adherence across antipsychotic agents. Considering the
      measurement problems associated with each existing approach, we offered a new,
      medication episode-specific approach, which would provide a fairer comparison of
      the levels of treatment adherence across different antipsychotic agents.

PMID- 19851517
TI  - A qualitative motion analysis study of voluntary hand movement induced by music
      in patients with Rett syndrome.
AB  - Patients with Rett syndrome are known to respond well to music irrespective of
      their physical and verbal disabilities. Therefore, the relationship between
      auditory rhythm and their behavior was investigated employing a two-dimensional
      motion analysis system. Ten female patients aged from three to 17 years were
      included. When music with a simple regular rhythm started, body rocking appeared
      automatically in a back and forth direction in all four patients who showed the
      same rocking motion as their stereotyped movement. Through this body rocking,
      voluntary movement of the hand increased gradually, and finally became sufficient
      to beat a tambourine. However, the induction of body rocking by music was not
      observed in the other six patients who did not show stereotyped body rocking in a
      back and forth direction. When the music stopped suddenly, voluntary movement of
      the hand disappeared. When the music changed from a simple regular rhythm to a
      continuous tone without an auditory rhythm, the periodic movement of both the
      hand and body prolonged. Auditory rhythm shows a close relationship with body
      movement and facilitates synchronized body movement. This mechanism was
      demonstrated to be preserved in some patients with Rett syndrome, and stimulation
      with music could be utilized for their rehabilitation.

PMID- 19851518
TI  - Treatment of refractory complex partial seizures: role of vigabatrin.
AB  - Vigabatrin (VGB) is an antiepileptic drug that was designed to inhibit GABA
      transaminase, and increase levels of gamma-amino-butyric acid (GABA), a major
      inhibitory neurotransmitter in the brain. VGB has demonstrated efficacy as an
      adjunctive antiepileptic drug for refractory complex partial seizures (CPS) and
      for infantile spasms (IS). This review focuses on its use for complex partial
      seizures. Although VGB is well tolerated, there have been significant safety
      concerns about intramyelinic edema and visual field defects. VGB is associated
      with a risk of developing bilateral concentric visual field defects. Therefore,
      the use of VGB for complex partial seizures should be limited to those patients
      with seizures refractory to other treatments. Patients must have baseline and
      follow-up monitoring of visual fields, early assessment of its efficacy, and
      ongoing evaluation of the benefits and risks of VGB therapy.

PMID- 19851519
TI  - Late- versus early-onset geriatric depression in a memory research center.
AB  - OBJECTIVE: To contrast early-onset (<60 years) and late-onset (>60 years)
      depression in geriatric patients by evaluating differences in cognition, vascular
      comorbidity and sociological risk factors. Both patient groups were compared with
      normal subjects. MATERIALS AND METHODS: We recruited 76 patients with depressive
      symptoms (37 late onset and 39 early onset) and 17 normal controls matched by age
      and educational level. All subjects were assessed using a semistructured
      neuropsychiatric interview and an extensive neuropsychological battery. Vascular
      and sociological risk factors were also evaluated. RESULTS: We found a
      significant variation in performance between depressive patients and normal
      controls in most cognitive functions, especially memory (P < 0.0001), semantic
      fluency (P < 0.0001), verbal fluency, and digit-symbol (P < 0.0001). Late-onset
      depression patients scored lower and exhibited more severe impairment in memory
      domains than early-onset depression patients (P < 0.05). Cholesterol levels and
      marital status were significantly (P < 0.05) different between the depressive
      groups. Both depressed groups (early- and late-onset) were more inactive than
      controls (P < 0.05; odds ratio: 6.02). CONCLUSION: Geriatric depression may be a
      manifestation of brain degeneration, and the initial symptom of a dementia. It is
      important to consider this in the treatment of patients that exhibit late-onset
      depressive symptoms.

PMID- 19851520
TI  - Update on the clinical use of the low-molecular-weight heparin, parnaparin.
AB  - Parnaparin is a low-molecular-weight heparin that has widely shown its efficacy
      and safety in prevention of venous thromboembolism, in the treatment of chronic
      venous disorders, and in the treatment of venous and arterial (stable and
      unstable angina, acute ST-segment elevation myocardial infarction) thrombosis.
      Parnaparin at the respective dosages of 3200, 4250, 6400, or 12800 IUaXa for a
      period ranging from 3 to 5 days to 6 months, is usually administered
      subcutaneously by means of once-daily regimen and is better tolerated than
      unfractionated heparin at the injection site. In the variety of commercially
      available low-molecular-weight heparins, parnaparin represents a useful
      therapeutic option, even though little evidence is available comparing the
      superiority or the equivalent efficacy and safety of parnaparin to that of the
      unfractionated heparin or placebo. This review summarizes the available
      literature on the use of parnaparin in different settings of cardiovascular
      diseases, including papers published during the past year and ongoing studies.

PMID- 19851521
TI  - Ankle brachial pressure index (ABPI): An update for practitioners.
AB  - Peripheral vascular disease affects some 12%-14% of the general population, and
      the majority of people with the disease are asymptomatic. The ankle brachial
      pressure index (ABPI) test is widely used by a diverse range of practitioners (in
      the community and hospital setting) in order to screen asymptomatic patients,
      diagnose patients with clinical symptoms, and to monitor patients who have had
      radiological or surgical intervention. This paper explains the theoretical basis
      of the ABPI test, as well as the relevance of the common modifications of the
      test. It explores the background to the quoted normal ranges for the ABPI test.
      It reviews the large body of literature that has developed on the association
      between ABPI and cardiovascular risk, as well as ABPI as a predictor for
      cardiovascular morbidity and mortality, highlighting the evidence that can inform
      practice. The review looks critically at the limitations of the ABPI test,
      providing practitioners with an evidence-based update on the importance and
      challenges of standardizing ABPI methodology. This paper highlights the influence
      of the key technical aspects of the ABPI test that all practitioners need to
      consider in order to be able to make more reliable and informed management
      decisions based on ABPI findings.

PMID- 19851522
TI  - Treatment of congenital fibrinogen deficiency: overview and recent findings.
AB  - Afibrinogenemia is a rare bleeding disorder with an estimated prevalence of
      1:1,000,000. It is an autosomal recessive disease resulting from mutations in any
      of the 3 genes that encode the 3 polypeptide chains of fibrinogen and are located
      on the long arm of chromosome 4. Spontaneous bleeding, bleeding after minor
      trauma and excessive bleeding during interventional procedures are the principal
      manifestations. We review the management of afibrinogenemia. Replacement therapy
      is the mainstay of treatment of bleeding episodes in these patients and plasma
      derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh
      frozen plasma are alternative treatments that should be used only when fibrinogen
      concentrate is not available. Secondary prophylactic treatment may be considered
      after life-threatening bleeding whereas primary prophylactic treatment is not
      currently recommended. We also discuss alternative treatment options and the
      management of surgery, pregnancy and thrombosis in these patients. The
      development of new tests to identify higher risk patients and of safer
      replacement therapy will improve the management of afibrinogenemia in the future.

PMID- 19851524
TI  - Five-year alendronate treatment outcome in older postmenopausal Japanese women
      with osteoporosis or osteopenia and clinical risk factors for fractures.
AB  - A retrospective study was conducted to evaluate the outcome of treatment with
      alendronate (ALN) for 5 years in postmenopausal Japanese women with an increased
      risk of fractures. Forty postmenopausal Japanese women with osteoporosis or
      osteopenia and clinical risk factors for fractures (mean age: 75.4 years) were
      analyzed; 33 patients were treated with alendronate and 7 were treated with
      alfacalcidol (ALF, controls) in an outpatient clinic run by general
      practitioners. The metacarpal bone mineral density (BMD) measured using a
      computed X-ray densitometer, urinary levels of cross-linked N-terminal
      telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase
      (ALP) were monitored during the 5-year treatment period. The urinary NTX and
      serum ALP levels decreased significantly in the ALN group, compared with the ALF
      group. The metacarpal BMD was sustained in the ALN group but decreased
      significantly in the ALF group; the difference between these two groups was also
      significant. The present study evaluated the outcome of treatment with ALN for 5
      years in postmenopausal Japanese women with osteoporosis or osteopenia and
      clinical risk factors for fractures. ALN successfully suppressed bone turnover
      and sustained the metacarpal BMD over the 5-year period of treatment in
      postmenopausal Japanese women with an increased risk of fractures.

PMID- 19851523
TI  - Patients with insulin-dependent diabetes or coronary heart disease following
      rehabilitation express serum fractalkine levels similar to those in healthy
      control subjects.
AB  - The chemokine and adhesion molecule fractalkine and its receptor CX(3)CR1 have
      emerged as interesting regulators in inflammation and related atherosclerosis.
      The pro-inflammatory status may be counteracted by appropriate treatment, such as
      in rehabilitation. We compared serum fractalkine concentrations of 46 patients
      with coronary heart disease (CHD) and 47 insulin-dependent diabetic patients
      (IDDM) following rehabilitation with those of 50 control subjects. Following
      rehabilitation serum fractalkine levels (477 + or - 225 pg/mL) in CHD patients
      were similar to those in control subjects (572 + or - 205 pg/mL; P = 0.303),
      whereas fractalkine levels were lower in IDDM patients (430 + or - 256 pg/mL; P =
      0.042). No significant difference between CHD and IDDM patients was present (P =
      0.319). Postprandial hyperlipemia may influence inflammation; thus, we
      investigated fractalkine levels four and eight hours after inducing postprandial
      hyperlipemia. However, we did not find any significant alterations in CHD and
      diabetic patients, whereas the fractalkine levels in controls were reduced. In
      vitro, lipofundin used as a hyperlipemic stimulus was added to vessel wall cells
      and reduced fractalkine levels. Low fractalkine levels in patients attending
      rehabilitation indicate a beneficial effect of the rehabilitation procedure on
      innate inflammatory pathways, such as the chemokine and adhesion molecule
      fractalkine.

PMID- 19851525
TI  - Pemetrexed as first-line therapy for non-squamous non-small cell lung cancer.
AB  - Pemetrexed is a new cytotoxic agent that is a standard of care for the second
      line treatment of non-small cell lung cancer (NSCLC) and in combination with
      cisplatin in treatment of malignat pleural mesothelioma. It has been studied in
      numerous phase II and III trials in combination with different drugs or as single
      agent. Recently, pemetrexed has been approved in combination with cisplatin for
      the first-line treatment of patients with locally advanced or metastatic NSCLC
      other than squamous cell histology. The toxicity is acceptable and similar to
      that of other NSCLC regimens. The postinduction maintenance therapy with
      pemetrexed is being evaluated in a phase III, double-blind, placebo-controlled
      study.

PMID- 19851526
TI  - Safety and efficacy of telbivudine for the treatment of chronic hepatitis B.
AB  - Telbivudine was recently approved for the treatment of chronic hepatitis B. Phase
      III studies indicated its antiviral potency with 6- to 6.5-log copies/mL
      reductions in hepatitis B DNA levels at year 1, comparable to other potent agents
      such as entecavir or tenofovir. Genotypic resistance rates, however, reached 25%
      at year 2 in hepatitis B e-antigen positive subjects and 11% in hepatitis B e
      antigen negative subjects, preventing it from becoming a preferred first-line
      drug for hepatitis B. Furthermore, its signature resistance mutation (a change
      from methionine to isoleucine at position 204 in the reverse transcriptase domain
      of the hepatitis B polymerase) also confers cross-resistance to entecavir,
      lamivudine, and emtricitabine. Telbivudine is well tolerated, with elevations in
      creatine phosphokinase being the most common abnormality observed in clinical
      trials. Most often, elevations were asymptomatic. Future research in hepatitis B
      will focus on the best ways to use existing therapies, including telbivudine,
      sequentially or in combination in order to maximize viral suppression and
      minimize the development of antiviral resistance.

PMID- 19851527
TI  - The role of urate and xanthine oxidase in vascular oxidative stress: future
      directions.
AB  - Vascular oxidative stress has been shown to be a potent factor in the
      pathophysiology of endothelial dysfunction. Despite current optimal evidence
      based therapy, mortality from various cardiovascular disorders remains high. The
      search for newer, novel ways of attenuating endothelial dysfunction has yielded
      several new and exciting possibilities, one of which is the manipulation of urate
      levels using xanthine oxidase inhibitors. Agents such as allopurinol have shown
      marked improvements in vascular endothelial function in various cohorts at risk
      of cardiovascular events. Most of the evidence so far comes from smaller
      mechanistic studies. The few large randomized controlled trials have failed to
      show any significant mortality benefit using these agents. This article
      highlights the potential avenues of further research such as dose-response, and
      the potential for these agents to regress left ventricular hypertrophy. The role
      of newer agents such as febuxostat and oxypurinol are discussed as well as
      potential reasons why some of the current newer agents have failed to live up to
      the promising early-phase data. It is crucial that these remaining questions
      surrounding urate, xanthine oxidase and the role of various agents that affect
      this important oxidative stress-generating system are answered, and therefore
      these promising agents should not be discarded prematurely.

PMID- 19851528
TI  - Artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum
      malaria.
AB  - The World Health Organization strongly recommends artemisinin-based combination
      therapy (ACT) regimens for the treatment of uncomplicated Plasmodium falciparum
      malaria cases in endemic areas. Among the combinations of compounds that are
      available at present, excellent results have been obtained for the artemisinin
      derivative artemether, in a combination galenic preparation with lumefantrine
      (artemether-lumefantrine, AL). Here, the pharmacological properties and the
      therapeutic options of both substances are briefly reviewed and a cursory
      overview is given on recent trials that have compared the therapeutic effects of
      AL in the standard 6-dose regimen with other antimalarials and combinations. In
      order to ensure the most achievable and reliable adherence and compliance of
      children in the treatment of malaria, a dispersible formulation of AL is now
      attainable. Recent reports on the emergence of resistance to ACT regimens in
      Asia, however, are alarming.

PMID- 19851529
TI  - End-of-life care for persons with advanced chronic obstructive pulmonary disease:
      report of a national interdisciplinary consensus meeting.
AB  - While systemic shortcomings in meeting the needs of individuals with progressive
      chronic illnesses at the end of life have been well documented, there is growing
      interest in improving both care and quality of life for persons with advanced
      chronic obstructive pulmonary disease (COPD). For instance, the American Thoracic
      Society has issued an official statement on palliative care for patients with
      respiratory diseases, affirming that the prevention, relief, reduction and
      soothing of symptoms "without affecting a cure" must become an integral component
      of standard care. A recent Medline search located 1015 articles related to
      palliative or end-of life care for people with COPD published between 2001 and
      2008, compared with only 336 articles published before 2001. To address the needs
      of Canadian patients, an interdisciplinary consensus meeting, funded by the
      Canadian Institutes of Health Research and supported by the Canadian Thoracic
      Society, the Canadian Respiratory Health Professionals and the Canadian Lung
      Association was convened in Toronto, Ontario, on November 22, 2008, to begin
      examining the quality of end-of-life care for individuals with COPD in Canada.
      The present report summarizes the background to and outcomes of this consensus
      meeting.

PMID- 19851530
TI  - An atypical presentation of liver enzyme elevation resulting from bosentan use.
AB  - Hepatocellular enzyme elevation is a known side effect of both bosentan and
      atorvastatin. However, a rise in liver enzyme level not characteristic of either
      agent individually may represent a reaction to their combination or an atypical
      reaction to bosentan alone. The present case report describes a patient who had
      been taking atorvastatin for many years and was started on bosentan for chronic
      thromboembolic pulmonary hypertension. After 19 weeks of therapy, she developed
      severe liver enzyme elevation that necessitated the discontinuation of both
      bosentan and atorvastatin. Although the safety of reintroducing bosentan in such
      a case is unknown, it was reintroduced in this patient because of the severity of
      her disease, the demonstrated treatment benefit and the lack of alternative
      treatment options. On reintroduction of bosentan alone, she again demonstrated
      significant liver enzyme elevation - this time occurring after only two doses.
      The present case highlights that bosentan can cause more rapid and severe
      hepatocellular enzyme elevation than previously believed, thus necessitating more
      frequent monitoring.

PMID- 19851531
TI  - Workers' compensation and mesothelioma.

PMID- 19851532
TI  - Filing for workers' compensation among Ontario cases of mesothelioma.
AB  - BACKGROUND/OBJECTIVE: For many types of cancer, disease attribution to
      occupational exposures is difficult. Mesothelioma, however, is a 'sentinel'
      occupational cancer associated with asbestos exposure. The present study linked
      workers' compensation claims data with cancer registry data to explore the
      completeness of reporting of mesothelioma to the Ontario Workplace Safety and
      Insurance Board (WSIB) according to characteristics of cases diagnosed among
      Ontario residents. METHODS: Two data sources were linked at the person level: the
      WSIB Occupational Disease Information and Surveillance System and the Ontario
      Cancer Registry. Filing rates were calculated as the proportion of Ontario Cancer
      Registry mesothelioma cases (International Classification of Diseases - Oncology
      code 905) that linked to a WSIB-filed cancer claim. Filing rates were calculated
      for the period 1980 to 2002, and trends were calculated by year, age and county
      of residence at diagnosis. RESULTS: The filing rate for compensation has
      increased little over the past 20 years, reaching a high of 43% in 2000. Overall,
      filing rates were highest among pleural mesothelioma cases among men (range 27%
      to 57%). Filing rates were highest among individuals 50 to 59 years of age and
      declined substantially throughout the retirement years. There was substantial
      variation in filing rates by area of residence, with the highest rate being in
      Lambton County, Ontario. CONCLUSION: The filing rate for compensation in Ontario
      was much lower than the estimated proportion of cases eligible for compensation.
      The increased filing rate in Lambton County was likely related to this
      community's awareness of the association between asbestos and mesothelioma.
      Physicians can play an important role in educating patients of their potential
      entitlement to compensation benefits.

PMID- 19851533
TI  - Improvement in health-related quality of life after lung transplantation.
AB  - BACKGROUND/OBJECTIVE: Traditional survival outcomes do not reflect the effects on
      the health-related quality of life (HRQL) of patients. HRQL following lung
      transplantation has not been studied systematically. The Health Utilities Index
      (HUI) is a family (HUI2 and HUI3) of measures of HRQL that has not been
      previously used to assess HRQL in lung transplantation. The objective of the
      present study was to assess the impact of lung transplantation on patient's HRQL
      using the HUI. METHODS: A total of 43 patients completed a battery of
      questionnaires before lung transplantation, and at three months and six months
      after lung transplantation. The 15-item questionnaire (HUI2 and HUI3) was used.
      Overall scores were based on a conventional scale (0.00 = dead, 1.00 = perfect
      health). Mental health was assessed by the Hospital Anxiety and Depression Scale.
      Adherence to medication and exercise were assessed by Morisky's and Godin's
      questionnaires, respectively. RESULTS: Sixty-five per cent of the patients were
      men, with a mean age of 53 years (range 18 to 67 years). The mean overall HUI3
      score for the lung transplant candidates (0.57) was much lower than for the lung
      transplant recipients (0.82) at six months post-transplantation. This difference
      was clinically important and statistically significant (P<0.05 [paired t test,
      degrees of freedom (df) = 35]). Differences in mean Hospital Anxiety and
      Depression Scale scores after transplantation were statistically significant
      (P<0.05 [paired t test, df=35]). After six months, transplant recipients were
      more adherent to medication (P<0.05 [X2 test, df=1]). Recipients were able to
      increase the duration of exercise at all levels of intensity. CONCLUSION: Lung
      transplantation improved the patients' HRQL and adherence to medication. Anxiety
      levels persisted six months after transplantation but depression levels had
      decreased significantly.

PMID- 19851534
TI  - Clinical manifestations and treatment of adult-onset asthma and periocular
      xanthogranuloma.
AB  - BACKGROUND: Adult-onset asthma and periocular xanthogranuloma is an uncommon and
      recently described disease. Little is known about the condition because only a
      few case reports and series are available. OBJECTIVE/METHODS: To describe the
      clinical manifestations, lung physiology, and response to systemic treatment of
      three patients with adult-onset asthma and periocular xanthogranuloma, followed
      by a review of the literature. RESULTS: Three men, with an age at diagnosis
      ranging from 48 to 51 years, presented with right periorbital swelling, asthma
      and chronic rhinosinusitis. The patients' lung physiology was consistent with
      airway obstruction. Diagnosis was established by periorbital biopsy. All patients
      received oral corticosteroids for their periorbital swelling, without significant
      clinical response. Two patients received oral methotrexate, with nearly complete
      resolution of periorbital swelling. A third patient received oral azathioprine,
      without clinical response. The three patients had improvement of their asthma
      with inhaled steroids/long-acting bronchodilator, and immunosuppressive
      medication. CONCLUSION: A triad consisting of periorbital swelling, asthma and
      chronic rhinosinusitis should raise the suspicion of adult-onset asthma and
      periocular xanthogranuloma. Oral methotrexate should be considered as an
      alternative to corticosteroids in the treatment of this disorder.

PMID- 19851535
TI  - Catheter-related right atrial thrombus and pulmonary embolism: a case report and
      systematic review of the literature.
AB  - Central venous catheters (CVCs) are commonly used in clinical practice. One of
      the foremost complications associated with their use is the potential for
      symptomatic or asymptomatic thrombosis. CVC thrombosis, in turn, may not only
      result in vascular and catheter occlusion but also infection, pulmonary embolism,
      and formation of right heart thromboemboli. Thrombi within cardiac chambers are
      associated with an increased risk of mortality due to their potential for
      embolization to the pulmonary vasculature. We describe the case of a 77-year-old
      man, who was successfully thrombolyzed following detection of a right atrial
      thrombus and hemodynamically significant pulmonary embolism resulting from
      thrombus formation on the tip of a peripherally inserted central catheter (PICC).
      The present article is the first report of a PICC-related right atrial thrombus
      in an adult treated with thrombolysis. A systematic review of the literature
      suggests that the true incidence of this complication may be underestimated
      because the diagnosis may not be considered in asymptomatic and symptomatic
      patients, or may be missed by transthoracic echocardiography. The present case
      highlights the importance of maintaining a high index of suspicion for
      thromboembolic complications and heparin-induced thrombocytopenia in patients
      with CVCs or a PICC. It also underscores the important role of transesophageal
      echocardiography and thrombolysis in the diagnosis and management, respectively,
      of right heart thromboemboli with associated pulmonary embolism.

PMID- 19851539
TI  - A dipolar gas of ultracold molecules.
AB  - Ultracold polar molecular gases promise new directions and exciting applications
      in collisions and chemical reactions at ultralow energies, precision
      measurements, novel quantum phase transitions, and quantum information science.
      Here we briefly discuss key experimental requirements for observing strong dipole
      dipole interactions in an ultracold dipolar gas of molecules. We then survey
      current experimental progress in the field with a focus on our recent work
      creating a near quantum degenerate gas of KRb polar molecules [Ni et al.,
      Science, 2008, 322, 231].

PMID- 19851538
TI  - Colloidal transport on magnetic garnet films.
AB  - This article reports several recent discoveries related to the controlled
      transport of paramagnetic colloidal particles above magnetic garnet films. The
      garnet films are thin uniaxial ferromagnetic films in which ferromagnetic domains
      can be organized into symmetric patterns consisting of stripes or bubbles and
      generate strong local magnetic field gradients. Application of an external
      homogeneous magnetic field on a larger scale compared to the spatial periodicity
      of the magnetic pattern in the film modulates the potential generated at its
      surface and induces the controlled motion of colloidal particles placed above the
      film. Several novel dynamical regimes are observed and reported, from localized
      trajectories to direct particle transport, depending on the geometry of the
      underlying magnetic pattern and on the parameters, which control the external
      driving field, such as frequency, strength and direction. Moreover, we show that
      this strategy allows separation and sorting of bi-disperse particle systems based
      on the particle size as well as the transport of chemical or biological cargoes
      attached to the colloidal carriers. Controlled transport of micro-sized cargoes
      (chemical or biological) by colloidal particle carriers in a microfluidic
      environment can bring significant contributions in several fields from targeted
      drug delivery to the realization of precise fluid-based micro-scale devices.

PMID- 19851540
TI  - A novel pulse isotopic exchange technique for rapid determination of the oxygen
      surface exchange rate of oxide ion conductors.
AB  - We demonstrate the use of a novel pulse (18)O-(16)O isotopic exchange technique
      for the rapid determination of the oxygen surface exchange rate of oxide ion
      conductors while simultaneously providing insight into the mechanism of the
      oxygen exchange reaction, which contributes to the efficient development of
      devices incorporating these solids, such as solid oxide fuel cells and oxygen
      transport membranes.

PMID- 19851541
TI  - Photo-induced electron recombination dynamics in CdSe/P3HT hybrid
      heterojunctions.
AB  - Since the demonstration of efficient hybrid photovoltaic devices using CdSe/P3HT,
      a number of different QD/polymer molecular solar cells have been investigated.
      However, considerably less attention has been paid to the photo-induced processes
      occurring in these devices, in particular the strong dependence that device
      efficiencies show upon QD concentration. This study aims to shed more light on
      this dependence by monitoring these processes occurring at the QD/polymer
      interface, namely, exciton formation, charge separation and undesired charge
      recombination.

PMID- 19851542
TI  - Electron transport and recombination in dye-sensitized solar cells made from
      single-crystal rutile TiO2 nanowires.
AB  - Contrary to expectations, the electron transport rate in dye-sensitized solar
      cells made from single-crystal rutile titanium dioxide nanowires is found to be
      similar to that measured in dye-sensitized solar cells made from titanium dioxide
      nanoparticles.

PMID- 19851543
TI  - Generalization of the continuous symmetry measure: the symmetry of vectors,
      matrices, operators and functions.
AB  - In this paper we generalize a method for evaluating the continuous symmetry
      measure, which is a quantitative estimate of the degree of symmetry of a given
      object. The generalization makes it possible to calculate the degree of symmetry
      content for any mathematical entity that is part of metric spaces such as
      vectors, matrices, operators and functions. Furthermore, by this new approach one
      can calculate the symmetry-content values for any compact symmetry groups either
      finite or infinite. An advantage of the new methodology is the ability to
      investigate analytically problems of symmetry changes. Examples of symmetry
      evaluation calculations are provided, including mixing of ideal gases, evaluation
      of the symmetry content of a Hamiltonian operator, the 2p(z) orbital of the
      hydrogen atom, and more.

PMID- 19851544
TI  - Chapman-Enskog expansion for multi-particle collision models.
AB  - Particle-based simulation methods for fluid flow follow a discrete time dynamics
      of subsequent streaming and collision events. The algorithm considered here,
      called stochastic rotation dynamics, involves collisions between an arbitrary
      number of partners; all particles that happen to be in the same cell of a
      randomly positioned grid interact at once by prescribed rules. I show, in two
      dimensions, how a multi-particle generalization of the Enskog equation can be
      derived from the Liouville equation and how the hydrodynamic equations can be
      obtained by a Chapman-Enskog expansion. The resulting macroscopic equations
      contain a collisional contribution to the transport coefficients, absent in
      earlier Chapman-Enskog approaches, which agrees exactly with previously known
      results from other kinetic theories. This approach opens up a powerful,
      systematic route to deriving hydrodynamic equations for particle-based models,
      which is generalizable to models with active particles.

PMID- 19851545
TI  - Coulomb-only second-order perturbation theory in long-range-corrected hybrid
      density functionals.
AB  - We have been investigating the combination of a short-range density functional
      approximation with long-range random phase approximation (RPA) correlation, where
      the direct RPA correlation is constructed using only Coulomb (i.e., not
      antisymmetrized) two-electron integrals. Our group's recently demonstrated
      connection between RPA and coupled cluster theory suggests investigating a
      related method: second-order Moller-Plesset perturbation theory correlation (MP2)
      constructed using only Coulomb integrals. This new "JMP2" method is related to
      the scaled-opposite-spin SOS-MP2 approximation [Y. Jung, R. C. Lochan, A. D.
      Dutoi and M. Head-Gordon, J. Chem. Phys., 2004, 121, 9793], which is also
      constructed using only Coulomb integrals. While JMP2 and SOS-MP2 yield identical
      results for closed shell systems, they have important differences for open
      shells. We show here that both JMP2 and SOS-MP2 provide a reasonable treatment of
      long-range correlation when combined with a short-range exchange-correlation
      functional. Remarkably, JMP2's explicit inclusion of (approximate) like-spin
      correlation effects provides significant improvements over SOS-MP2 for
      thermochemistry.

PMID- 19851546
TI  - Boron fullerenes B(32+8k) with four-membered rings and B32 solid phases:
      geometrical structures and electronic properties.
AB  - Based on ab initio calculations, we have studied the geometrical, electronic
      properties and chemical bonding of boron fullerenes B(32+8k) (0 < or = k < or =
      7) with four-membered rings and B(32) solid phases. The relative energies and the
      energy gaps between the highest occupied molecular orbital (HOMO) and the lowest
      unoccupied molecular orbital (LUMO) have been calculated, showing that the
      stabilities grow with the increase of fullerene size, where the smallest cage
      B(32) bears the largest HOMO-LUMO gap. The frontier orbitals of B(32+8k) show
      some similarities with those of the corresponding carbon fullerenes C(24+6k),
      implying that they may have similar chemical properties. It is found that B(32)
      cages can condense to form solid phases of simple cubic (sc), face-centered cubic
      (fcc), body-centered cubic (bcc), and body-centered tetragonal (bct) structures,
      where the bct phase is observed to be the most stable. Electronic structure
      calculations reveal that the sc, fcc and bcc phases of B(32) solids are metallic,
      but the bct phase is a semimetal.

PMID- 19851547
TI  - Production of hydrogen from reactions of methane with boranes.
AB  - The reactions of methane with different hydrides have been investigated using
      quantum chemical calculations (MP2 and CCSD(T) methods with the aug-cc-pVnZ one
      electron functions extrapolated to the basis set limits). The hydrides of the
      elements of the second and third row, and also GaH(3), with an electronegativity
      smaller than the value of hydrogen (LiH, Li(2)H(2), BeH(2), NaH, MgH(2), BH(3),
      AlH(3), B(2)H(6), Al(2)H(6), SiH(4), PH(4) and GaH(3)) have been considered.
      Reactions of CH(4) with either BH(3) or LiH are characterized by the lowest
      energy barriers. Reactions using the known methylated derivatives of boranes with
      methane follow a similar mechanism. Calculated results strongly suggest the
      possible use of boranes as reagents in the reactions with methane to produce
      molecular hydrogen.

PMID- 19851548
TI  - Theoretical study of atmospheric clusters: HNO3-HCl-H2O.
AB  - Nitric acid, hydrochloric acid and water can form stable aggregates with
      atmospheric implications, for instance at the surface of polar stratospheric
      clouds. The structure, stability and chemical properties of these ternary
      complexes are studied by means of high level theoretical calculations (hybrid DFT
      B3LYP method along with aug-cc-pVQZ basis set). From the many possible systems
      that these molecules could form, only 15 are found to yield stable structures,
      well characterized by a minimum in their potential energy surfaces. These
      aggregates are studied in detail. They can be collected in three families,
      according to the role played by each species in the different hydrogen bonding
      links that result and provide the basis for the stabilization of the clusters.
      Water and HCl can be H-donors to almost every O atom of HNO(3), which in turn can
      donate its H atom to the other two molecules. Two special cases are found, one in
      which H(2)O plays a central role, and another with a three-dimensional structure,
      in contrast to the basically planar frame of the other clusters. Bonding
      properties are investigated for the whole series using AIM methods. The
      elongation of the H-Cl bond as a consequence of the aggregate creation is
      inspected in detail, as it may provide a clue to the lability of this molecule
      with implications in atmospheric processes. The Gibbs free energy calculated for
      these clusters shows that some of them could form spontaneously in the range of
      temperatures of the stratosphere.

PMID- 19851549
TI  - Temperature measurement of single evaporating water droplets in a nitrogen flow
      using spontaneous Raman scattering.
AB  - The evaporation dynamics of stationary water droplets held within an
      electrodynamic trap are investigated in a nitrogen flow of variable velocity. In
      particular, the influence of the nitrogen gas flow on the temperature of the
      evaporating water droplets is studied. By applying a contact free measurement
      technique, based on spontaneous Raman scattering, time averaged and time resolved
      measurements of temperature in the droplet volume are compared. This technique
      determines the temperature from an intensity ratio in the OH stretching band of
      the Stokes-Raman scattering after calibration. The measured trends in temperature
      over the first 5 s of evaporation are found to be in agreement with theoretical
      calculations of the heat and mass transfer rates.

PMID- 19851550
TI  - Spin-coated and PECVD low dielectric constant porous organosilicate films studied
      by 1D and 2D solid-state NMR.
AB  - In the research field of the sub-65 nm semiconductor industry, organosilicate
      SiOCH films with low dielectric constant (k < 2.4) need to be developed in order
      to improve the performance of integrated circuits [International Roadmap for
      Semiconductors (ITRS), San Jose, CA, 2004]. One way to produce SiOCH films of low
      dielectric constant is to introduce pores into the film. This is usually obtained
      in two steps. Firstly, co-deposition of a matrix precursor, with a sacrificial
      organic porogen, either by plasma enhanced chemical vapor deposition (PECVD) or
      spin-coating. Secondly, application of a specific thermal treatment to remove the
      porogen and create the porosity. This last step can be improved by adding to the
      thermal process a super-critical CO(2) treatment, an UV irradiation or an
      electronic bombardment (e-beam). In this study, the two deposition processes as
      well as the various treatments applied to eliminate the porogens were evaluated
      and compared using high-resolution solid-state NMR. For this purpose, hybrid
      (containing porogens) and porous films were extensively characterized on the
      basis of their (1)H, (13)C and (29)Si high-resolution NMR spectra. Information
      was obtained concerning the crosslinking of the Si skeleton. Spectral features
      could be correlated to the processes used. Isotropic chemical shift analyses and
      2D correlation NMR experiments were used to show the existence and nature of the
      interactions between the matrix precursor and the organic porogen.

PMID- 19851551
TI  - Infrared-optical double resonance spectroscopic measurements and high level ab
      initio calculations on a binary complex between phenylacetylene and borane
      trimethylamine. Understanding the role of C-H...pi interactions.
AB  - The structure of the binary complex between phenylacetylene and borane
      trimethylamine has been elucidated using IR-UV double resonance spectroscopy in
      combination with high level ab initio calculations at the CCSD(T) level. Borane
      trimethylamine interacts primarily through multiple C-H...pi interactions with
      the pi electron density of the benzene ring in phenylacetylene. CCSD(T) level
      calculations provide reliable estimates for the interaction energy and free
      energy, which are in accord with the experimental observations. The DFT-SAPT
      calculations point out that the dispersion interaction plays a major role in the
      formation of the experimentally observed complex, along with a sizable
      contribution from electrostatics.

PMID- 19851552
TI  - Thermodynamic basis of chiral recognition in a DNA aptamer.
AB  - Chiral separation is an important issue in pharmaceutical research and
      industries, because most organic compounds and biological molecules, including
      many drugs and food additives, are chiral compounds. DNA aptamers are a new group
      of chiral selectors; however, there still exists deficiencies in the
      understanding of the molecular basis of their chiral recognition. Herein, a
      comparative study of the DNA aptamer binding with L-argininamide (L-Arm) and its
      enantiomer (D-Arm) is investigated by spectroscopic and calorimetric methods. The
      effect of various experimental conditions such as temperature, pH and salt
      concentration on the L-Arm and D-Arm binding properties was studied in order to
      provide information about the chiral recognition mechanism of the DNA aptamer. An
      isothermal titration calorimetry study reveals that both L-Arm and D-Arm binding
      with the aptamer are enthalpy driven and entropy cost processes. The protonated
      amino group of both L-Arm and D-Arm participates in electrostatic interaction and
      this interaction is stronger for D-Arm than L-Arm binding with the aptamer. From
      the opposite behavior of the heat capacity change of the two enantiomers, we
      could suggest that L-Arm and D-Arm bind at different binding sites of the
      aptamer, resulting in different conformations of the binding complexes. In the
      binding mechanism, electrostatic interaction provided by the protonated amino
      group with the aptamer and the conformational change of the nucleic acid upon
      binding are major processes involved for chiral recognition in the DNA aptamer.
      This study provides information on chiral separation of D- and L-argininamide by
      the aptamer, which can be successfully achieved by varying the operation
      temperature based on the opposite heat capacity dependence of the enantiomers
      binding with the DNA.

PMID- 19851553
TI  - Outperformed electrochromic behavior of poly(ethylene glycol)-template
      nanostructured tungsten oxide films with enhanced charge transfer/transport
      characteristics.
AB  - Porous tungsten oxide films of nanocrystalline tungsten oxide embedded in an
      amorphous tungsten oxide matrix have been synthesized via poly(ethylene glycol)
      (PEG)-template sol-gel technique with peroxopolytungstic acid precursor. The
      effects of PEG addition on the microstructure and electrochromic performance of
      the tungsten oxide films are investigated. Charge transfer/transport properties
      in the tungsten oxide films are studied by electrochemical impedance spectroscopy
      (EIS) as well. Triclinic tungsten oxide film is formed in the absence of PEG. The
      PEG-template tungsten oxide film demonstrates an electrochromic performance
      superior to that of the crystalline tungsten oxide film, including larger
      transmittance modulation and coloration/bleaching efficiency as well as faster
      response times. EIS measurements indicate that faster charge-transfer rates at
      the tungsten oxide/electrolyte interface and larger Li(+) diffusion coefficients
      in tungsten oxide are achieved in the PEG-template film. We suggest that the PEG
      template tungsten oxide film with a porous crystalline/amorphous nanostructure
      provides an effective means for charge transfer/transport to encourage its
      superior electrochromic performance.

PMID- 19851554
TI  - Surface-specific overgrowth of platinum on shaped gold nanocrystals.
AB  - Controlling the shape and composition of metal nanocrystals can be beneficial for
      tuning the optical or catalytic properties in a variety of applications. In this
      study, surface-specific overgrowth of platinum was found on shaped gold
      nanocrystals of cubes, octahedra and spheres. Platinum overgrowth was observed on
      the planar faces of gold cubes, while the overgrowth occurred at the vertices of
      gold octahedra, indicating that platinum was selectively reduced on the Au (100)
      surface for each gold nanocrystal shape. The platinum nuclei covered the entire
      surface for gold spheres, which don't have well-defined surfaces. As the Pt/Au
      ratio increased, a full platinum shell was formed. Solution-based UV-Vis
      absorption spectra of the composite nanocrystals showed that the absorption peak
      was red-shifted with increasing platinum coverage. The optical response of a
      single composite nanocrystal was measured by dark field microscope, which also
      demonstrated a red shift in the scattering spectrum with increasing platinum
      coverage. The extent of a red shift depended on the shape and composition of the
      composite nanocrystals.

PMID- 19851555
TI  - Water-solubilization of alkyloxo(methoxo)porphyrinatoantimony bromides.
AB  - In order to develop water-soluble porphyrins,
      alkyloxo(methoxo)porphyrinatoantimony bromides (alkyl = hexyl (1a), decyl (1b),
      dodecyl (1c), tetradecyl (1d), octadecyl (1e)) were prepared. 1 had more than 1
      mmol dm(-3) of solubility in water. From the dependence of the half-width of the
      bands in the absorption spectra and surface tension on the concentration of 1, it
      was estimated that 1b-d were present as aggregates in concentrations higher than
      10 micromol dm(-3). From the NMR analysis in D(2)O, it was deduced that the
      alkyloxo ligands of 1 were arranged alternately in the aggregates. The diameter
      of the aggregates of 1 in water was determined to be around 100 nm by the dynamic
      light scattering method. Since the solubilities of
      di(methoxo)tetraphenylporphyrinatoantimony bromide and 5-(4'-decyloxyphenyl)
      10,15,20-triphenylporphyrinato(dimethoxo)antimony(v) bromide were low, it was
      calculated that the long alkyl axial ligands were requisite for the high
      solubility in water.

PMID- 19851556
TI  - Formation and stability of nanoemulsions with mixed ionic-nonionic surfactants.
AB  - A simple, low-energy two-step dilution process has been applied with binary
      mixtures of ionic-nonionic surfactants to prepare nanoemulsions. The systems
      consist of water/DDAB-C(12)E(5)/decane. Nanoemulsions were obtained by dilution
      of concentrates located in bicontinuous microemulsion or lamellar liquid crystal
      phase regions. The nanoemulsions generated were investigated both by contrast
      variation small-angle neutron scattering (SANS) and dynamic light scattering
      (DLS). The SANS profiles show that C(12)E(5) nanodroplets suffer essentially no
      structural change on incorporation of the cationic DDAB surfactant, except for
      increased electrostatic repulsive interactions. Interestingly, SANS indicated
      that the preferred droplet sizes were hardly affected by the surfactant mixture
      composition (up to a DDAB molar ratio (m(DDAB)/(m(DDAB) + m(C(12)E(5))) of 0.40)
      and droplet volume fraction, phi, between 0.006 and 0.120. No notable changes in
      the structure or radius of nanoemulsion droplets were observed by SANS over the
      test period of 1 d, although the droplet number intensity decreased significantly
      in systems stabilized by C(12)E(5) only. However, the DLS sizing shows a marked
      increase with time, with higher droplet volume fractions giving rise to the
      largest changes. The discrepancy between apparent nanoemulsion droplet size
      determined by DLS and SANS data can be attributed to long-range droplet
      interactions occurring outside of the SANS sensitivity range. The combined SANS
      and DLS results suggest flocculation is the main mechanism of instability for
      these nanoemulsions. The flocculation rate is shown to be significantly retarded
      by addition of the charged DDAB, which may be due to enhanced electrostatic
      repulsive forces between droplets, leading to improved stability of the
      nanoemulsions.

PMID- 19851557
TI  - Restricted active space spin-flip configuration interaction approach: theory,
      implementation and examples.
AB  - A new formulation of the spin-flip (SF) method is presented. The electronic wave
      function is specified by the definition of an active space and through alpha-to
      beta excitations from a Hartree-Fock reference. The method belongs to the
      restricted active space (RAS) family, where the CI expansion is restricted by
      classifying the molecular orbitals in three subspaces. Properties such as spin
      completeness, variationality, size consistency, size intensivity, and orbital
      invariance are discussed. The implementation and applications use a particular
      truncation of the wave function, with the inclusion of hole and particle
      contributions such that for fixed active space size, the number of amplitudes is
      linear in molecular size. This approach is used to investigate single and double
      bond-breaking, the singlet-triplet gap of linear acenes, electronic transitions
      in three Ni(II) octahedral complexes, the low-lying states of the 2,5
      didehydrometaxylylene (DDMX) tetraradical and the ground state multiplicity of 28
      non-Kekule structures. The results suggest that this approach can provide a quite
      well balanced description of nearly degenerate electronic states at moderate
      computational cost.

PMID- 19851558
TI  - Argon clusters embedded in helium nanodroplets.
AB  - Electron impact ionization of argon clusters embedded in helium droplets is
      investigated. Superior mass resolution makes it possible to distinguish between
      nominally isobaric cluster ions. An abundance maximum for ArHe(12)(+) is
      unambiguously confirmed; the spectra also prove the formation of Ar(2)He(n)(+)
      complexes that had been claimed to fragment into pure Ar(2)(+). Distributions of
      larger argon cluster ions containing up to 60 atoms closely resemble
      distributions observed upon electron impact or photoionization of bare argon
      clusters; caging and evaporative cooling provided by the helium matrix do not
      suffice to quench fragmentation of the nascent argon cluster ions. Intriguing
      abundance anomalies are observed in distributions of argon cluster ions that
      contain water, nitrogen or oxygen impurities. The strong abundance of
      Ar(55)H(2)O(+), Ar(54)O(2)(+) and Ar(54)N(2)(+) contrasts with the virtual
      absence of slightly larger cluster ions containing the corresponding impurities.
      The features are probably related to enhanced cluster ion stability upon closure
      of the second icosahedral shell but the difference in magic numbers (54 versus
      55) and the well-known reactivity of charged argon-nitrogen complexes suggest
      structural differences.

PMID- 19851559
TI  - Forster resonance energy transfer (FRET) with a donor-acceptor system adsorbed on
      silver or gold nanoisland films.
AB  - We observed Forster resonance energy transfer (FRET) with a covalently linked
      donor-acceptor pair D-A consisting of two naphthalene groups acting as the donors
      and a benzofurazan group acting as the acceptor and adsorbed onto Ag or Au
      nanoisland films. The use of metal nanoisland films, which caused a strong
      enhancement of the Raman signal, permitted description of the adsorption
      mechanism onto the two metals. The intense fluorescence response of molecular
      adsorbates and the different behavior of the antenna on Ag and Au nanoislands are
      partly explained in terms of the radiating plasmon model.

PMID- 19851560
TI  - Preparation of Langmuir-Blodgett films of aligned sepiolite fibers and
      orientation of methylene blue molecules adsorbed on the film.
AB  - Sepiolite is a clay mineral with a fibrous morphology; the fibers possess
      rectangular channels along the fiber direction, and have cation-exchange ability.
      Amphiphilic octadecylammonium cations (ODAH(+)) spread at an interface between
      the air and a dispersion of sepiolite fibers have hybridized with the fibers to
      form a floating monolayer. Surface pressure-molecular area isotherms did not
      indicate clear collapse points of the hybrid monolayers. Observation of the
      hybrid films on glass plates by atomic force microscopy revealed that the
      sepiolite fibers preferred to be aligned perpendicularly to the compression
      direction, and that some fibers overlapped upon compression or even before
      compression. Out-of-plane and in-plane X-ray diffraction patterns of the hybrid
      film showed that the fibers were not only aligned by the compression but oriented
      around the fiber direction. Electronic spectra of methylene blue cations (MB(+))
      adsorbed on the hybrid film indicated the presence of monomers and dimers of
      MB(+). The absorption intensity due to the monomer was dependent on the
      polarization direction of the incident beam; interestingly, the monomers were
      spontaneously oriented along the sepiolite fiber direction but the dimers were
      not oriented. By comparison with the results of rhodamine 6G adsorbed on the
      film, the monomers of MB(+) would probably be present in the channels of
      sepiolite fibers, while the dimers would be adsorbed on the external surface of
      the fibers.

PMID- 19851561
TI  - Response of CPO-27-Ni towards CO, N2 and C2H4.
AB  - Coordinatively unsaturated Ni(2+) atoms in CPO-27-Ni form linear adducts with
      molecular nitrogen. The framework responds to the adsorption-modifying
      vibrational properties and local structure around adsorbing sites. The present
      paper deals with a fundamental infrared (IR) study of the interaction of gases on
      a microporous adsorbent metallorganic framework CPO-27-Ni containing, after
      solvent removal, coordinatively unsaturated Ni(2+) atoms [Dietzel et al., Chem.
      Commun. 2006, 959]. CO, N(2) and C(2)H(4) have been chosen. Notwithstanding the
      relative medium (CO and C(2)H(4)) and weak (N(2)) adsorption enthalpies and the
      low equilibrium pressures adopted (100-10(-3) mbar) the CPO-27-Ni framework
      responds promptly and reversibly to the adsorption process, modifying
      significantly both vibrational properties and local structure around Ni(2+)
      adsorbing sites as determined by a parallel EXAFS investigation locating the N(2)
      molecule 2.27 +/- 0.03 A apart from Ni(2+). For both N(2) and C(2)H(4), IR
      spectra have been discussed and carefully compared with literature data.
      Isosteric heat of adsorption of the Ni(2+)...N(2) complex formation has been
      evaluated from temperature dependent IR study to be -DeltaH(ads) = 17 kJ mol(-1).

PMID- 19851562
TI  - Molecular dynamics simulations of amorphous hydrogenated carbon under high
      hydrogen fluxes.
AB  - We study the flux dependence of the carbon erosion yield and the hydrogen
      enrichment of the surface in the high flux regime at 10(28) ions per m(2) s and
      higher by using molecular dynamics (MD). We simulate an amorphous hydrogenated
      carbon sample exposed to high flux hydrogen bombardment with a hydrogen energy of
      10 eV at surface temperatures of 700 and 1000 K. As interaction potential the
      reactive empirical bond order potential of Brenner-Beardmore is taken and energy
      dissipation is simulated with the Berendsen thermostat. The simulation results
      show that the carbon erosion yield is higher for higher sample temperatures but
      does not show a strong dependence on the hydrogen flux. Hence, the hydrogen
      enrichment in the upper surface layer observed in the simulations most likely
      does not contribute to the erosion yield reduction in the experiments.
      Furthermore, the composition of the eroded material shows a slight increase in
      CH, C(2)H and C(2)H(2) for higher fluxes, whereas species with more hydrogen, C
      atoms and C(2) are decreased. However, the H : C ratio in the eroded material
      shows no flux dependence.

PMID- 19851563
TI  - Neon-matrix spectroscopic and theoretical studies of the reactivity of titanium
      dimer with diatomic ligands: comparison of reactions with nitrogen and carbon
      monoxide.
AB  - The reactivity of diatomic titanium with molecular carbon monoxide has been
      investigated in solid neon at very low temperature. In contrast to the
      spontaneous reaction observed between Ti(2) and N(2), our results show that the
      formation of dititanium oxycarbide (OTi(2)C) from the condensation of effusive
      beams of Ti and CO in neon matrices involves several intermediate steps including
      one metastable intermediate. In the absence of electronic excitation, only
      formation of a Ti(2)(CO) complex occurs spontaneously during the reaction at 9 K
      of ground state Ti(2) and CO, as reported in solid argon by Xu, Jiang and Tsumori
      (Angew. Chem. Int. Ed., 2005, 44, 4338). However, during deposition or following
      electronic excitation, this species rearranges into a new species: the more
      stable, OTi(2)C oxycarbide form. Several low-lying excited states of OTi(2)C are
      also observed between 0.77 and 0.89 eV above the ground state, leading to a
      complex sequence of interacting vibronic transitions, merging into a broad
      continuum above 1 eV. Observations of Ti(2)(12)C(16)O, Ti(2)(13)C(16)O and
      Ti(2)(12)C(18)O and natural titanium isotopic data enable the identification of
      four fundamental vibrations in the ground electronic state and two others in the
      first two excited states. Quantum chemical calculations predict an open-shell
      (1)A(g) ground state with Ti-C and Ti-O distances close to 184 pm, and 91 degrees
      for the TiCTi and TiOTi bond angles, and give fundamental frequencies in good
      agreement with observation. The reaction paths of the Ti(2) + N(2) --> Ti(2)N(2)
      and Ti(2) + CO --> Ti(2)(CO) --> OTi(2)C have been investigated and a reaction
      scheme is proposed accounting for the similarities in nature and properties of
      the final products, as well as explaining the observation of a coordination
      complex with Ti(2) only in the case of the carbonyl ligand.

PMID- 19851564
TI  - Experimental and theoretical investigations of CB8-: towards rational design of
      hypercoordinated planar chemical species.
AB  - We demonstrated in our joint photoelectron spectroscopic and ab initio study that
      wheel-type structures with a boron ring are not appropriate for designing planar
      molecules with a hypercoordinate central carbon based on the example of CB(8),
      and CB(8)(-) clusters. We presented a chemical bonding model, derived from the
      adaptive natural density partitioning analysis, capable of rationalizing and
      predicting planar structures either with a boron ring or with a carbon atom
      occupying the central hypercoordinate position. According to our chemical bonding
      model, in the wheel-type structures the central atom is involved in delocalized
      bonding, while peripheral atoms are involved in both delocalized bonding and two
      center two-electron (2c-2e) sigma-bonding. Since carbon is more electronegative
      than boron it favors peripheral positions where it can participate in 2c-2e sigma
      bonding. To design a chemical species with a central hypercoordinate carbon atom,
      one should consider electropositive ligands, which would have lone pairs instead
      of 2c-2e peripheral bonds. Using our extensive chemical bonding model that
      considers both sigma- and pi-bonding we also discuss why the AlB(9) and FeB(9)(-)
      species with octacoordinate Al and Fe are the global minima or low-lying isomers,
      as well as why carbon atom fits well into the central cavity of CAl(4)(2-) and
      CAl(5)(+). This represents the first step toward rational design of nano- and
      subnano-structures with tailored properties.

PMID- 19851565
TI  - Reevaluation of absolute luminescence quantum yields of standard solutions using
      a spectrometer with an integrating sphere and a back-thinned CCD detector.
AB  - We reevaluate the absolute fluorescence and phosphorescence quantum yields of
      standard solutions by using a novel instrument developed for measuring the
      absolute emission quantum yields of solutions. The instrument consists of an
      integrating sphere equipped with a monochromatized Xe arc lamp as the light
      source and a multichannel spectrometer. By using a back-thinned CCD (BT-CCD) as
      the detector, the sensitivity for spectral detection in both the short and long
      wavelength regions is greatly improved compared with that of an optical detection
      system that uses a conventional photodetector. Using this instrument, we
      reevaluate the absolute fluorescence quantum yields (Phi(f)) of some commonly
      used fluorescence standard solutions by taking into account the effect of
      reabsorption/reemission. The value of Phi(f) for 5 x 10(-3) M quinine bisulfate
      in 1 N H(2)SO(4) is measured to be 0.52, which is in good agreement with the
      value (0.508) obtained by Melhuish by using a modified Vavilov method. In
      contrast, the value of Phi(f) for 1.0 x 10(-5) M quinine bisulfate in 1 N
      H(2)SO(4), which is one of the most commonly used standards in quantum yield
      measurements based on the relative method, is measured to be 0.60. This value is
      significantly larger than Melhuish's value (0.546), which was estimated by
      extrapolating the value of Phi(f) for 5 x 10(-3) M quinine bisulfate solution to
      infinite dilution using the self-quenching constant. The fluorescence quantum
      yield of 9,10-diphenylanthracene in cyclohexane is measured to be 0.97. This
      system can also be used to determine the phosphorescence quantum yields (Phi(p))
      of metal complexes that emit phosphorescence in the near-infrared region: the
      values of Phi(p) for [Ru(bpy)(3)](2+) (bpy = 2,2'-bipyridine) are estimated to be
      0.063 in water and 0.095 in acetonitrile under deaerated conditions at 298 K,
      while that in aerated water, which is frequently used as a luminescent reference
      in biological studies, is reevaluated to be 0.040.

PMID- 19851566
TI  - Supramolecular self-assembly nature of a novel thermotropic liquid crystalline
      polymer containing no conventional mesogens.
AB  - Two-dimensional correlation infrared spectroscopy (2DIR) and a newly developed
      perturbation correlation moving window (PCMW) technique was employed to study the
      precise supramolecular self-assembly nature of poly[di(butyl)vinyl terephthalate]
      (PDBVT), a novel thermotropic liquid crystalline polymer which can self-assemble
      into a two-dimensional hexagonal columnar (2D Phi(H)) phase without conventional
      mesogens. PCMW had found the weak phase transition temperature to be about 85
      degrees C, and further divided the "S or anti-S" shaped spectral variations into
      three evolving stages. 2DIR results indicated that carbonyl groups acted as the
      starting point of molecular motions upon heating, and had a significant influence
      on the formation of the 2D Phi(H) phase. Based on the additional motion sequence
      of symmetric and asymmetric C-H stretching vibrations, the whole self-assembly
      process of PDBVT on the mesoscale, whose backbones experienced "extension
      distortion-slight extension" consecutive motions was elucidated.

PMID- 19851567
TI  - The CO-Ne van der Waals complex: ab initio intermolecular potential energy,
      interaction induced electric dipole moment and polarizability surfaces, and
      second virial coefficients.
AB  - The intermolecular potential energy, interaction induced electric dipole moment
      and polarizability surfaces of the CO-Ne van der Waals complex are calculated
      using coupled cluster methods and the d-aug-cc-pVTZ basis set extended with a set
      of 3s3p2d1f1g midbond functions placed in the middle of the van der Waals bond.
      After fitting the interaction properties to appropriate analytical functions the
      surfaces are further used in semiclassical calculations of the pressure, the
      dielectric and the refractivity second virial coefficients of the system. The
      interaction potential energy surface has a single minimum (-49.9952 cm(-1)),
      which corresponds to R = 3.383 A and theta = 79.4 degrees. The computed
      dielectric second virial coefficient B(epsilon) approximately -0.27 cm(6) mol(-2)
      around the room temperature.

PMID- 19851568
TI  - A molecular dynamics simulation study of LiFePO4/electrolyte interfaces:
      structure and Li+ transport in carbonate and ionic liquid electrolytes.
AB  - We have performed atomistic molecular dynamics (MD) simulations of the (010)
      surface of LiFePO(4) in contact with an organic liquid electrolyte (OLE),
      ethylene carbonate : dimethyl carbonate (3 : 7) with approximately 1 mol kg(-1)
      LiPF(6), and an ionic liquid-based electrolyte (ILE), 1-ethyl 3-methyl
      imidazolium: bis(fluorosulfonyl)imide (EMIM(+) : FSI(-)) with approximately 1 mol
      kg(-1) LiFSI. Surface-induced structure that extends about 1 nm from the
      LiFePO(4) surface was observed in both electrolytes. The electrostatic potential
      at the LiFePO(4) surface was found to be negative relative to the bulk
      electrolyte reflecting an excess of negative charge from the electrolyte
      coordinating surface Li(+). In the ILE system negative surface charge is
      partially offset by a high density of EMIM(+) cations coordinating surface
      oxygen. The electrostatic potential exhibits a (positive) maximum about 3 A from
      the LiFePO(4) surface which, when combined with the reduced ability of the highly
      structured electrolytes to solvate Li(+) cations, results in a free energy
      barrier of almost 4 kcal mol(-1) for penetration of the interfacial electrolyte
      layer by Li(+). The resistance for bringing Li(+) from the bulk electrolyte to
      the LiFePO(4) surface through this interfacial barrier was found to be small for
      both the OLE and ILE. However, we find that the ability of EMIM(+) cations to
      donate positive charge to LiFePO(4)/electrolyte interface may result in a
      significant decrease in the concentration of Li(+) at the surface and a
      corresponding increase in impedance to Li(+) intercalation into LiFePO(4),
      particularly at lower temperatures.

PMID- 19851569
TI  - Concerted orientation induced unidirectional water transport through
      nanochannels.
AB  - The dynamics of water inside nanochannels is of great importance for biological
      activities as well as for the design of molecular sensors, devices, and machines,
      particularly for sea water desalination. When confined in specially sized
      nanochannels, water molecules form a single-file structure with concerted dipole
      orientations, which collectively flip between the directions along and against
      the nanotube axis. In this paper, by using molecular dynamics simulations, we
      observed a net flux along the dipole-orientation without any application of an
      external electric field or external pressure difference during the time period of
      the particular concerted dipole orientations of the molecules along or against
      the nanotube axis. We found that this unique special-directional water
      transportation resulted from the asymmetric potential of water-water interaction
      along the nanochannel, which originated from the concerted dipole orientation of
      the water molecules that breaks the symmetry of water orientation distribution
      along the channel within a finite time period. This finding suggests a new
      mechanism for achieving high-flux water transportation, which may be useful for
      nanotechnology and biological applications.

PMID- 19851570
TI  - Spectroscopic investigation of the species involved in the rhodium-catalyzed
      oxidative carbonylation of toluene to toluic acid.
AB  - A spectroscopic investigation of complexes used to catalyze the oxidative
      carbonylation of toluene to p-toluic acid was conducted. Rhodium complexes were
      analyzed by (103)Rh and (13)C NMR, UV-visible spectroscopy, and infrared
      spectroscopy. In the presence of vanadium and oxygen, the resting state of the Rh
      catalyst was found to exist as a Rh(III) complex with carbonyl and
      trifluoroacetate ligands, consistent with the structure Rh(CO)(2)(TFA)(3). The
      (13)C NMR spectrum of Rh((13)CO)(2)(TFA)(3) complex exhibited a carbonyl peak
      with an unusual degree of shielding, which resulted in the appearance of the
      carbonyl peak at an unprecedented upfield position in the (13)C NMR spectrum.
      This shielding was caused by interaction of the carbonyl group with the
      trifluoroacetate ligand. In the absence of oxygen, the Rh(III) complex reduced to
      Rh(I), and the reduced form exhibited properties resembling the catalyst
      precursor. Structures and spectroscopic properties calculated using density
      functional theory agreed closely with the experimental results. The vanadium co
      catalyst used to reoxidize Rh(I) to Rh(III) was similarly characterized by (51)V
      NMR and UV-visible spectroscopy. The oxidized species corresponded to
      [(VO(2))(TFA)](2), whereas the reduced species corresponded to (VO)(TFA)(2). The
      spectroscopic results obtained in this study confirm the identity of the species
      that have been proposed to be involved in the Rh-catalyzed oxidative
      carbonylation of toluene to toluic acid.

PMID- 19851571
TI  - Laser-induced 3D alignment and orientation of quantum state-selected molecules.
AB  - A strong inhomogeneous static electric field is used to spatially disperse a
      rotationally cold supersonic beam of 2,6-difluoroiodobenzene molecules according
      to their rotational quantum state. The molecules in the lowest-lying rotational
      states are selected and used as targets for 3-dimensional alignment and
      orientation. The alignment is induced in the adiabatic regime with an
      elliptically polarized, intense laser pulse and the orientation is induced by the
      combined action of the laser pulse and a weak static electric field. We show that
      the degree of 3-dimensional alignment and orientation is strongly enhanced when
      rotational state-selected molecules, rather than molecules in the original
      molecular beam, are used as targets.

PMID- 19851573
TI  - [Analysis of the implantation of the healthcare network for victims of accidents
      and violence following the guidelines of the National Policy for the Reduction of
      Morbidity and Mortality from Violence and Accidents].
AB  - In this article we problematize the results of an investigation entitled
      'Diagnostic Analysis of the National Policy for Reduction of Morbidity and
      Mortality from Accidents and Violence (PNRMVA)' and present some thoughts for
      discussion. Based on a quantitative and qualitative analysis of the implantation
      of this policy in five Brazilian state capitals--Recife, Rio de Janeiro, Manaus,
      Curitiba and Brasilia and vicinities--along with the participation of local
      academic institutions we performed a diagnosis of the situation. The article
      presents evaluative information regarding: the profile of morbidity and mortality
      from accidents and violence; the adequacy of mobile and fixed pre-hospital
      emergency services, hospital services and rehabilitation services to preventing
      the described epidemiological profile; the training of the professionals dealing
      with these traumas; surveillance and monitoring of violence and accidents as well
      as support for studies and investigations into the issue. Aimed at proposing a
      debate, the article concludes raising questions about the advances made in the
      implementation of the policy, about the fragilities of the system and about the
      possibilities for an efficient implementation of the PNRMVA guidelines.

PMID- 19851574
TI  - [The analysis of the implementation of the National Policy for the Reduction of
      Morbidity and Mortality from Violence and Accidents highlights the problems at
      the Unified Health System].

PMID- 19851575
TI  - [Dialoguing on the implementation of the National Policy for the Reduction of
      Morbidity and Mortality from Violence and Accidents in five Brazilian capitals].

PMID- 19851576
TI  - [About the national health policy for reducing accidents and violence nowadays].

PMID- 19851578
TI  - [Unintentional injuries at the Emergency Department Injury Surveillance System-
      Brazil, 2006].
AB  - In 2006, the Brazilian Ministry of Health established the Injury Surveillance
      System Network in Sentinel Services (Rede VIVA) to describe data on injuries
      victims treated at emergency departments (ED), especially minor injuries which do
      not cause deaths and hospitalization. This study describes the characteristics of
      unintentional injuries victims treated in these EDs by means of a transversal
      descriptive study with data coming from EDs located in 35 municipalities with the
      highest injury rates. The data were collected during 30 consecutive days in an
      alternated 12-hour shift. There were a total of 41,677 patients with
      unintentional injuries, mainly among males (64.8%), people aged 20 to 29 years
      (23.0%) and low level of education (45.8%). Falls were the main cause (40.1%
      overall), followed by transport related injuries (26.6% overall). The more
      frequent place of occurrence were public streets (36.3% overall) and residences
      (33.6% overall). The body parts most affected were upper members (42.7%), lower
      members (42.0%) and head/face (29.2%). The injury surveillance in sentinel
      services allows collecting timeless data about minor cases which is essential for
      planning and implementing preventive measures.

PMID- 19851579
TI  - [Profile of unintentional injuries involving children under ten years of age in
      emergency departments--Brazil, 2006 to 2007].
AB  - External causes occupy a high position in the morbidity and mortality profile of
      youth and children in Brazil, configuring an important public health problem and
      demanding the deepening of the studies on its characteristics and magnitude. This
      article describes the profile of emergency care for accidents suffered by
      children (< 10 years of age) seen at emergency public in some services in Brazil
      in 2006 and 2007. The data were obtained from survey surveillance component of
      the Sentinel Service Surveillance System for Violence and Accidents (VIVA), of
      the Ministry of Health. Children represented about 20% of emergency visits by
      accidents, with male sex predominance and pre scholars' (2-5 years of age). The
      greater proportion of accidents (60%) occurred in the household, followed by
      public ways, school, leisure and sport practice places. Falls and burns had
      greater participation in the younger age group (< 1), while transport accidents
      and other types of accidents presented greater frequency among children age 2 to
      5. It is necessary to develop education programs since pre school and along the
      community, aiming of warning about risks and the need of adopt safe behavior in
      relation to the household environment and the development phase of the child.

PMID- 19851580
TI  - [Validation of the portuguese version of the Mini-Social Phobia Inventory (Mini
      SPIN)].
AB  - Social phobia (also known as social anxiety disorder) is a severe mental disorder
      that brings distress and disability. The aim of this study was validate to the
      Portuguese language the Mini-Social Phobia Inventory (Mini-SPIN) in a
      populational sample. We performed a discriminative validity study of the Mini
      SPIN in a sample of 644 subjects (Mini-SPIN positive group: n = 218 and
      control/negative group: n = 426) of a study of anxiety disorders' prevalence in
      the city of Santo Andre-SP. The Portuguese version of the Mini-SPIN (with score
      of 6 points, suggested in the original English version) demonstrated a
      sensitivity of 95.0%, specificity of 80.3%, positive predictive value of 52.8%,
      negative predictive value of 98.6% and incorrect classification rate of 16.9%.
      With score of 7 points, was observed an increase in the specificity and positive
      predictive value (88.6% and 62.7%), while the sensitivity and negative predictive
      value (84.8% and 96.2%) remained high. The Portuguese version of the Mini-SPIN
      showed satisfactory psychometric qualities in terms of discriminative validity.
      In this study, the cut-off of 7, was considered to be the most suitable to
      screening of the generalized social phobia.

PMID- 19851581
TI  - [Actions and possibilities of accidents prevention with children in daycare at
      Fortaleza, Ceara State].
AB  - This paper describes the daily of infantile education teachers in day-cares in
      the city of Fortaleza, Ceara, Brazil as well as the developed actions and the
      possibilities of prevention accidents' with children, in this educative space of
      health care. It is a descriptive study, using a qualitative approach that
      involved 17 day care teachers working at the 6th Regional Executive Office
      (Fortaleza, Ceara, Brazil) in the year of 2004. A semi-structured interview was
      used to collect the data, which was analysed using the Collective Subject
      Discourse (CSD) technique. The results showed that teachers believe that this
      type of accident is preventable through family orientation, physical
      modifications of house spaces and creation and enforcement of specific laws. They
      recognise children's agility and curiosity, which facilitate the occurrence of
      accidents. In their practices, they report and suggest vigilance, physical
      changes at the day care centers, and education, through orientation directed to
      children, teachers, parents (or care givers), and the community. Therefore,
      health care professionals should share their 'caring' practice with professionals
      in the educational area, not only in order to prevent accidents and other human
      health afflictions, but also to expand concepts that contribute Health Promotion.

PMID- 19851582
TI  - [The risk of the military profession in the city of Rio de Janeiro in 'peace
      time': the perception of the troop].
AB  - This study aims at determining the risk perception of Army Military concerning
      common activities at Military Units of troop in Rio de Janeiro. This mapping
      might allow taking preventive action when preparing these professionals, reducing
      their vulnerability. The present study is descriptive and used a qualitative
      methodological approach. The informers were selected into four military units and
      divided in three groups: eight officers, eight sergeants and eight
      corporal/soldiers, summing up 24 informers. It was possible to identify three
      risk categories noticed by the military in their common Military Units
      activities: (a) The risk of being a military in a city where urban violence
      reached the level there is in Rio de Janeiro city; (b) the risk of accidents and;
      (c) the risk of injuries or chronic pathology related to the exposure to
      activities that need proper protection, noticed by a number of informants. It can
      be concluded that the local violence has a great influence on the health of the
      military, due to the fact that modifies substantially the daily routines and
      their emotions during the work and that the perception the military have of the
      risks of their activities is focused on the present moment.

PMID- 19851583
TI  - [Domestic violence in the conception of health professionals trainers].
AB  - This article identifies the conceptions and suggestions of professors of medicine
      and nursing courses about the insertion of this subject in the formation of their
      students. An exploratory research was carried out using a questionnaire applied
      to coordinators of disciplines in such courses at public and private universities
      in the cities of Rio de Janeiro and Cuiaba. Many of them recognizes violence as a
      health problem, although 40.7% of medicine professors and 71.1% of nursing
      professors of the two cities discusses this subject in their classes. The
      medicine professors suggests the insertion of the violence subject in their
      students formation with visits to institutions, meeting groups with people in
      violence situations and interviews with experienced professionals of the area.
      The nursing professors prefer resources such as films and videos, seminaries and
      conferences. Gaps were also identified in the students and professors formation,
      which do not feel able to discuss this thematic. It is indicated that a
      renovation in the curriculum is urgently necessary.

PMID- 19851584
TI  - [Discourse analysis: research potentialities to gender violence].
AB  - In the last few years we see the growing use of the terms 'discourse' and
      'discourses analysis' in academic and research contexts, frequently without a
      precise definition. This fact opens space for critics and mistakes. The aim of
      this paper is to show a brief contextualization of discursive studies, as well as
      tasks/steps to Discourse Analysis process by the Social Construcionism
      perspective. As examples we used fragments of an interview with a Family Doctor
      about gender violence. In the results we detach the potential of Discourse
      Analysis to deconstruct the existing discourses to subsequently (re)construction
      in the way to a more holistic view about gender violence problem.

PMID- 19851586
TI  - [Neither ill, nor victim: the self-injury in the emergency care].
AB  - This paper shows concepts and practices of health professionals regarding cases
      of self-injury. It is problematized the existent gap between professionals
      training based in the biomedical model and practices, in which are presented
      dimension not considered for biomedicine. The empiric reference is a public
      emergency hospital in the city of Sao Paulo. The qualitative nature study was
      developed by observing attendances, consults to medical records and interviews
      with health professionals. The underlying question is related to intelligibility
      model of the illness, based in the body as a privileged locus of care, and
      illness as accidental event. Contradictively, self-injury situations (suicide
      attempts, drug and alcohol abuse) are analyzed as intentionally events,
      consequence of a choice, implicating no identification of their authors as
      patients or victims of care.

PMID- 19851585
TI  - [Suicidal attempts and obits in the district of Independencia, Ceara State,
      Brazil].
AB  - The objective of this work was to analyze the occurrence of suicidal attempts and
      deaths that happened in the district of Independencia, Ceara State, Brazil, in
      2005. A case study was carried out, including attempts and deaths by suicide. A
      data gathering source was composed out of the SIS (Mortality Information System)
      and of the SIH (Hospital Admittance System), regarding the year 2005, besides
      documentary research on district hospital records. Out of six recorded obits, two
      happened in the age group of 10 to 19, three from 20 to 29, and one from 30 to
      59. One half of the suicide victims were male, and the prevailing method was
      hanging. Considering the attempts, most of them concentrated in the age group of
      10 to 19, prevailing females (seven cases). The main signs and symptoms presented
      by victims, before exerting suicidal attempt were: sadness, loss of sleep,
      anorexia, nervousness, will to cry, and aggressiveness; there also was some kind
      of affective relationship among those persons. It was concluded that the events
      recorded in the district of Independencia must be analyzed as a social fact,
      highlighting the small time interval between the deaths and attempts and, the
      existence of relational links among the victims.

PMID- 19851587
TI  - [Media and drugs: a documental analysis of the Brazilian writing media between
      1999 and 2003].
AB  - This paper aims to analyze the kind of information published by the Brazilian
      'written media' about drugs. It was examined articles about drugs in a national
      circulation magazine between 1999 and 2003, through an analysis of content. A
      total of 481 articles were found. 'Consumption' was the most appeared topic. The
      most quoted drugs were: cocaine (21%), marijuana (19%), alcoholic beverages (12%)
      and cigarettes (12%). This research also showed that 57% of the articles were
      related to cigarettes, its harmful effects, whereas alcohol had the same amount
      of articles showing it as a good or a bad substance for the human being and
      considered the most addictive drug (23%). On the other hand, cocaine was related
      to drug dealing (30%). In general, cocaine and marijuana were in focus in the
      media while alcohol and solvents had less prominence considering the
      epidemiologic data of use. We can notice that there is an incompatibility between
      the media focus and the profile of drug consumption in Brazil, that could
      influence the person's beliefs about certain substances and public politics about
      drugs in Brazil.

PMID- 19851588
TI  - [Invisible sequels of traffic accident: the post-traumatic stress disorder as a
      public health problem].
AB  - This document consolidates the results of the Seminar 'Invisible Squeals of
      Traffic Accidents' carried out as part of the Project 'Social and Economic
      Impacts of Traffic Accidents in Brazilian Highways'. To begin with, the
      characteristics of post-traumatic stress disorder related to traffic accidents
      are identified, as well as its potential victims, symptoms, diagnosis, as well as
      risk and protection factors for the development of the disease. Next, follows a
      brief description of projects and research developed in Brazil and abroad in the
      field. Finally, post-traumatic stress disorder is analyzed as a matter of Public
      Health and policy recommendations are presented as a suggestion to reduce the
      sociopsychological consequences of traffic accidents violence.

PMID- 19851589
TI  - [Impact of violence on the health of families at Fortaleza, Ceara State].
AB  - The study describes the impact of the violence on the quality of life of the
      families, which were attended at the Relatives and Friends Violence Victims
      Association (ARFVV) in Fortaleza, Ceara State. The case study was accomplished
      among five mothers that were involved in a NGO on the battle against the
      violence. The semi-structured interview, the participation at the institution's
      meetings and the documental research were the data collecting techniques, being
      these last ones, submitted to the thematic analysis and discussed according to
      the literature and Letters of Health Promotion. The impacts caused by the
      violence comprise the physical, emotional and social family's health, cause
      changes on behavior between the members, and lead to the increasing of smoking,
      drinking, social isolation and exacerbate revolt feelings, vengeance and
      pessimism. The NGO's work has been important to support the families on the
      conflicts overcoming, health familiar restoration, redeeming the self
      expectation, the hope on the justice and social mobility. The health of families'
      victims from violence is affected on the biological, emotional and social
      aspects, favoring the process of sickness. These have appealed to the support
      from NGOs to transform the 'victim condition' - violence hostage to the
      'responsible citizenship' - guardians of peace on the battle against the urban
      violence.

PMID- 19851590
TI  - [The mortality differentials by violence against adolescents according to living
      conditions strata and race/color in the city of Recife].
AB  - An ecological study was conducted in order to analyze the differences in
      mortality by violence against adolescents according to living conditions strata
      and race/color in Recife in the period from 1998 to 2004. The average mortality
      coefficient for violence during this period was calculated for the city and by
      living conditions strata. The data related to the violence were obtained from the
      System of Information on Mortality. For the race/color, proportions have been
      calculated and within the period of 1999 to 2004. The mortality rate for violent
      deaths against adolescents for the city was of 88.24 per 100 thousand
      adolescents, being 46.93 in stratum I, of 'better living condition', and 95.00 in
      stratum III, of 'worse condition of life'. Amongst the violent deaths, 92.45%
      reached black adolescents and 7.55% white ones. The results show up inequalities
      in mortality by violence disclosing a tragic panorama in the trajectory of life
      of the adolescents.

PMID- 19851591
TI  - [Alcohol-related injuries in emergency departments in Brazil, 2006 and 2007].
AB  - Alcohol-related injuries are an important public health issue worldwide. The
      objective of this study was to describe the epidemiology of alcohol intake
      perceived by interviewers among injury victims seen at emergency departments in
      selected Brazilian cities. Cross-sectional data were collected from the injury
      surveillance system based on sentinel health services recently implemented in the
      country through intentional sampling in 2006 and 2007 and analyzed in Epi Info
      3.5.1. Alcohol intake perception was higher in violence-related injuries than in
      unintentional injuries (37.9% versus 8%). For violence-related injuries, highest
      proportions of alcohol intake perception were observed among males (43.7%), 20 to
      39 years old (45.3%), blacks (40.5%), and low schooling level victims (40.3%).
      Settings where these injuries occurred with the highest concerned proportions
      were taverns (78.2%) and public places (39.5%). Higher alcohol intake perception
      was observed in assaults (39.1%), suicide attempts (25.4%), transport-related
      injuries (16.8%), and falls victims (5.9%).

PMID- 19851592
TI  - [Stopping with the criminality: a way out of youths involved in traffic of drugs
      in slums in the city of Rio de Janeiro].
AB  - This article deals with the lives of young egress of drug traffic in the slums of
      the city of Rio de Janeiro. Its main objective is to examine the circumstances
      and the specific conditions that drive young people to abandon this illegal work
      activity. The method used to collect data was the topical life story in order to
      find out how 30 youths, from seven slums, had got involved until their departure
      from the 'movement'. Data shows that youths, entering trafficking, had an
      expectation of empowerment. With time, this attitude will wane, as they realize
      they are living with situations of betrayal, punishment and fear. The process for
      getting out occurs when the youth begins to question this type of work and sees
      other ways of life, more consistent with their aspirations. The facts conclude
      that when getting an early involvement in organized crime it leaves them
      physically and emotionally exhausted, as selling drugs is an ongoing
      confrontation through constant episodes of armed conflicts and arms dealing.

PMID- 19851593
TI  - [Traffic injuries among youth in Goiania, Goias State].
AB  - Traffic injuries are currently one of the world's main public health issues in
      both developed and developing countries. This study aimed to describe the
      circumstances involved in traffic accidents and the profile of the victims
      attended at Hospital de Urgencias de Goiania, age group of 15 to 24 years and
      residents in Goiania--Brazil. It is a prospective cross-sectional study carried
      out from August 2005 to August 2006 by systematic sampling. Data were analyzed by
      descriptive statistics. Most of the 301 victims were male; with average age of
      19.94 + 2.73 years, and drivers. Motorcycles (67.33%) and bicycles (16.67%) were
      the most frequent transportation. Accidents usually occurred around 6pm, on
      Fridays and Sundays. The victims were generally traveling/walking to/from
      exercise, sports, school, recreational or entertainment activities. Suspicion of
      alcohol use was reported in 15.16% of the cases. More motorcyclists believed that
      there was imprudence/ negligence in the accident than the cyclists. Security
      equipment was not used by 8.58% of motorcyclists and 95.45% of cyclists.
      Educational measures for motorcyclists and surveillance highlighting the night
      time and weekends are needed.

PMID- 19851594
TI  - [Diagnostic analysis of the rehabilitation services that attend victims of
      accidents and violence in Recife].
AB  - This paper aims to analyze the rehabilitation services in Recife, Brazil,
      confronting it with what the National Policy for Decreasing Morbimortality from
      Accidents and Violence (NPDMAV) professes. Six units of rehabilitation services
      were analyzed; five were from municipal administration and the other was an ONG
      on an agreement with SUS. A partial structured interview was conducted with the
      person in charge for the Attention to the Disable Person's Health aiming to map
      the network. Also a questionnaire was applied to the managers of the six services
      aiming to identify the unit and its activities, structure and organization. The
      Rehabilitation Assistance network in Recife do not meet the NPDMAV guidelines as
      it presents: decreased number of services/programs; lack of a multidisciplinary
      team; lack of technological support; deficient joint intra and inter sectors;
      little interaction between the victim and his family to reinsertion into family
      and social life; and still incipient prevention and promotion actions. In
      conclusion, there is an effort to adequate the actions to this population group;
      however there are relevant covering deficits of people, equipments, information
      and articulation registers among the various levels of this health network.

PMID- 19851595
TI  - ['Broken hearted teenagers': adolescents that had gone through suicide attempt].
AB  - This report describes the reasons of the suicidal behavior in adolescents, taking
      in this anthropologic analysis, the impact in the familiar and social context.
      The study was conducted during the period of March to August, 2005 using a
      qualitative approach and ethnography as methods. The participants of this study
      were 12 teenagers, assisted in an emergency hospital in Fortaleza, Ceara State,
      Brazil, for suicide attempt using any kind of mechanisms. As shown in the
      experiment's result, the main reason of the attempts was a broken heart, this as
      a reason of dating someone and others love relationship established between two
      persons. Not only broken heart was mentioned, there were also cases of problems
      with family bonds, the affection and the lack of attention to the individual
      adolescent. In this context, the inability of the health professional was very
      clear. Under the presented circumstances, the professional must come up with a
      new praxis approach. The suicide is a real fact present at the teenagers' life
      and it is necessary to redirect the Brazilian Unified Health System s philosophy
      and operational principles of the way health professionals cope with this
      demanding the society to embrace the politics that cares for the human being life
      and wellness.

PMID- 19851596
TI  - [Maxillo facial injuries in victims of violence at school environment].
AB  - This study investigated the presence of injuries in the maxillofacial complex in
      children and adolescents victims of physical violence in school environment.
      Forty-two proofs involved children and adolescents victims of physical violence
      in school in the years of 2003 and 2006 were analyzed. The data had been
      registered in specific form collecting the following variables: gender, age,
      perpetrator agent, localization of the injuries in the distinct regions of the
      body, type and number of injuries, existence of injuries in oral cavity and
      tissue involvement. It was observed that 61.9% of the victims were male (61.9%),
      age-group 13 to 17 years the most reached. In most of the cases (92.9%), the
      perpetrators were friends from school while teachers represented 7.1% of the
      cases. Injuries around the head and face were present in 69.1% of the sample,
      with 23.8% of the victims presenting injuries in the buccal cavity, all of the
      injuries were situated in soft tissues, mainly in the lips. It was evidenced to
      be high the existence of injuries in the buccal cavity of the victims of
      aggression in the school environment, confirming the importance of dentistry in
      the diagnosis of injuries around the head and face of the victims of physical
      abuse.

PMID- 19851597
TI  - [Gender centrality in the process of identity construction of women involved in
      drug trafficking].
AB  - The present article aims to discuss the specificities of crimes perpetrated by
      women, especially the female participation in drug trafficking in Rio de Janeiro,
      Brazil. In addition to that, it intends to distinguish female from male
      criminality. The study is based on reflections made through interviews conducted
      with eight women presenting a history of involvement in drug trafficking in the
      slums of Rio de Janeiro. Through a systemic discursive approach(1), the analysis
      investigates the micro and macro elements involved in the process of the
      construction of the participants' identity. Results show that women's motivations
      to enter, remain and drop drug trafficking are in great part determined by
      gender, which along with color and class shapes the roles performed and the
      places occupied by men and women in society.

PMID- 19851598
TI  - [Violence and impunity in check: problems and perspectives under the optics of
      the forensic anthropology in Brazil].
AB  - Forensic anthropology is playing an increasingly important role facing violence
      and impunity in many countries. A research performed at police stations of Civil
      Police and Forensic Institutes of six Brazilian capitals demonstrated that the
      practice of recover and positive identification of human remains has been
      neglected in different levels. The main problem is the lack of specific training
      of the professionals that accomplish the expertise in field and laboratory, but
      also the fact that no anthropological database of disappeared people is
      available. As a result of this situation, an expressive number of human remains
      leave the forensic institutes without positive identification, and criminal
      inquiries of homicides stay without resolution, contributing to the aggravation
      of the violence and impunity scenery that devastates the country.

PMID- 19851599
TI  - Recent advances and opportunities in research on lupus: environmental influences
      and mechanisms of disease.
AB  - We summarize research on mechanisms through which environmental agents may affect
      the pathogenesis of lupus, discuss three exposures that have been the focus of
      research in this area, and propose recommendations for new research initiatives.
      We examined studies pertaining to key mechanistic events and specific exposures.
      Apoptosis leading to increased production or decreased clearance of immunogenic
      intracellular self-antigens and defective apoptosis of autoreactive immune cells
      both have been implicated in the loss of self-tolerance. The adjuvant or
      bystander effect is also needed to produce a sustained autoimmune response.
      Activation of toll-like receptors is one mechanism through which these effects
      may occur. Abnormal DNA methylation may contribute to the pathogenesis of lupus.
      Each of the specific exposures has been shown, in humans or in mice, to act upon
      one or more of these pathogenic steps. Specific recommendations for the continued
      advancement of our understanding of environmental influences on lupus and other
      autoimmune diseases include the development and use of mouse models with varying
      degrees of penetrance and manifestations of disease, identification of molecular
      or physiologic targets of specific exposures, development and use of improved
      exposure assessment methodologies, and multisite collaborations designed to
      examine understudied environmental exposures in humans.

PMID- 19851600
TI  - [Contribution of popular education in domiciliary physiotherapeutic attendance].
AB  - The extension project of Physiotherapy in the Community is developed in the
      neighborhood of Grotao linked to the family health units, in the city of Joao
      Pessoa. The aim of this work is to value popular knowledge and practices. The
      domiciliary physiotherapeutical assistance to the light of the popular education,
      at the same time that it promotes assistance to the unassisted population,
      extends our vision of health as an educational process. In each domiciliary visit
      we observed the social reality of the popular layers and the problems these
      people face, reflecting in its state of health, being evident for us the partner
      economic conditionants of the process health-illness. This is observed that when
      carrying out domiciliary consultation on the basis of the principles of the
      popular education, it extents the perspective of the performance of the
      physiotherapist. This is so, because it is an education based on the dialogue,
      that proposes the exchange between scientific and popular knowledge, motivating
      the perspective of a commitment to the health together with the community.

PMID- 19851601
TI  - [Evaluation of emergency services of the hospitals from the QualiSUS program].
AB  - The aid lent by the emergency services is the object of this paper, which aims to
      assess the emergency service of the QualiSUS program. The study is descriptive
      with the application of a questionnaire to the responsible of the emergency
      services in eight hospitals. The emergency services were always overcrowded, and
      the causes pointed were the low resolutivity of basic attention and the
      precariousness of the hospital network. Contributing to this there is the primary
      care decreased resolutivity and the precariousness of the hospital network. Six
      hospitals do not manage the emergency service. The entrance system is not
      organized and only three hospitals work with risk classification. All of them
      refer difficulties with internal and external services. The hardest pathologies
      to refer to other services are the chronicles, neurological and social. The
      professionals do not have specific qualification and the precariousness job
      contracts do not contribute neither for the professional's fixation nor for his
      qualification. Clinical protocols are used by one service. It was noticed the
      influence of the QualiSUS in the hospitals. The failure of the health services
      network interferes with the emergency patient's profile. The investment of the
      QualiSUS cannot be restrained to the hospital. Emergency should be more
      integrated to the system and hospital. The qualification of human resources is
      indispensable as well as the bed's regulation.

PMID- 19851602
TI  - [Effectiveness of a health promotion in pre-school infants program in the city of
      Anapolis, Goias State].
AB  - This work aimed to analyze the assistance given by a health promotion in pre
      school infants program in the city of Anapolis, Goias State, as well as the forms
      of participation of the ones involved. Thus, statistical attendance dates were
      collected, as well as the realization of interviews with the respective parents
      and/or responsible for the infants, and also the ones, showing a sample of 119
      and 19 people, respectively. Analyzing the collected data, it can be concluded
      that the effectiveness of the program, considering the perceptions of the
      interviewed ones, is showed as satisfactory on its global aspect.

PMID- 19851603
TI  - [Healthy life expectancy to Brazilian elders, 2003].
AB  - The increase of the percentage of elderly population in Brazil and the increase
      in longevity incite a demand for information on the quantity of years spent in
      good health. The aim of the present study is to measure the life expectancy for
      the elderly of 60 years and above, by sex and age, in the year of 2003. The
      Sullivan method was used, which combined the life-table with the current
      experience of mortality and the self-perceived health. The mortality information
      was obtained from the life tables published by the IBGE (Brazilian Institute of
      Geography and Statistics), 2003. The self-perceived health was used and it was
      dichotomized in good and bad. This information came from the National Research of
      Household Sample (PNAD), 2003. The results indicate that women live longer, but
      spend a higher number of years perceiving their health as bad, as compared to
      men. The results also highlights to the need of considering the differences
      between sexes in relation to the demand for health care. It is also important to
      consider the need to have policies designed to allow the increase in the number
      of years that the elderly can live in good health conditions.

PMID- 19851604
TI  - [Bioethical analysis of the Brazilian Dentistry Code of Ethics].
AB  - The Brazilian Dentistry Code of Ethics (DCE), Resolution CFO-71 from May 2006, is
      an instrument created to guide dentists' behavior in relation to the ethical
      aspects of professional practice. The purpose of the study is to analyze the
      above mentioned code comparing the deontological and bioethical focuses. In order
      to do so, an interpretative analysis of the code and of twelve selected texts was
      made. Six of the texts were about bioethics and six on deontology, and the
      analysis was made through the methodological classification of the context units,
      textual paragraphs and items from the code in the following categories: the
      referentials of bioethical principlism--autonomy, beneficence, nonmaleficence and
      justice -, technical aspects and moral virtues related to the profession.
      Together the four principles represented 22.9%, 39.8% and 54.2% of the content of
      the DCE, of the deontological texts and of the bioethical texts respectively. In
      the DCE, 42% of the items referred to virtues, 40.2% were associated to technical
      aspects and just 22.9% referred to principles. The virtues related to the
      professionals and the technical aspects together amounted to 70.1% of the code.
      Instead of focusing on the patient as the subject of the process of oral health
      care, the DCE focuses on the professional, and it is predominantly turned to
      legalistic and corporate aspects.

PMID- 19851605
TI  - [The comprehension of the meanings that actors have about the growth and
      development monitoring program: a step to foster its qualification].
AB  - This paper aims to present a portion of a study aimed to evaluate the effects and
      impact of the educative component of the Growth and Development Monitoring
      Program in four Health Institutions in Medellin, Colombia, regarding the meanings
      that the significant adults (SA) and health team members (HTM) have about the
      Program and its outcomes. It was done a qualitative evaluative research under a
      multiple case study. There were found important differences in the meanings of
      the Program and its outcomes among the stakeholders reflecting differences in
      interests, priorities, and needs. For the HTM, the Program's axis is the child
      and the education process is guided to change SA behaviors. In contrast, the SA
      considers itself a part of the Program axis, as a subject, because his raising
      role is related to his own development and well being as well as the child's.
      'Raising' is a socio - historic, cultural and ontological category that should be
      at center of any early childhood care program. It is very important to understand
      the meanings of the Program and its outcomes for the stakeholders in order to
      make better planning, implementation and evaluation of childhood care programs.

PMID- 19851606
TI  - [Travelling citizens: the 'users' of the Brazilian Unified Health System and the
      meanings of its demand to the health care emergency services in the context of a
      process of assistential model reorientation].
AB  - Despite the emphasis of the territorial logic on the first level of the public
      health services network, the users of this health system come demonstrating a
      historical preference by emergency services. In order to try to understand this
      behavior, a Qualitative Research was developed, by means of interviews with 'Foci
      Groups' of public health services users, where it was searched to know their
      experiences, perceptions and opinions, looking for understanding how do they
      choose during their search for assistance. The users reject the 'norm' that
      defines the basic health care services of their territorial reference as their
      'entrance door', in favor of other parameters that were more significant for
      them. The arrangements of the health care organization have the meaning of
      barriers to the access. Moreover, the user's image in relation to the UBS is of
      great limitation. On the other hand, the emergency services present for them as
      spaces characterized by bigger capacity. The users demonstrate a significant
      indifference about the public health services. Besides, the uncertainty's images
      prevail in the SUS. But, according to its access necessity, the users learn
      social rules in the services and construct several strategies with the aim to
      open the doors of the health system.

PMID- 19851607
TI  - [Oral health conditions diagnostic in cerebral palsy individuals of Pelotas, Rio
      Grande do Sul State, Brazil].
AB  - Cerebral Palsy (CP) is an encephalic static lesion defined as a non-progressive
      disorder of movements and posture. It is usually associated with epilepsy,
      speaking, hearing and sight disorders and also mental retardation. Even though,
      people who have CP need special care for the prevention of factors linked to oral
      problems, in the odontological context, the literary information is contradictory
      when it comes to the incidence of oral diseases on patients who have cerebral
      palsy. In order to determine the oral health and associated factors conditions,
      an epidemiological research has been made in 41 children who have cerebral palsy.
      The variables taken into account were: social-economical aspects, risk factors
      for the development of oral diseases, access to odontological care, caries index,
      periodontal disease, malocclusion and dental fluorose. Children who were examined
      showed a higher level of gingivitis and caries experience, mainly on the primary
      dentition, and also severe malocclusions, factors that indicate the need of early
      intervention, whether with educational programs or healing assistance. The study
      has shown that, in addition to the quantitative necessity of care, it is also
      necessary to improve the quality of these patients' consultations.

PMID- 19851610
TI  - Side effects of publish-or-perish pressure on graduate studies.

PMID- 19851611
TI  - [Review of data quality dimensions and applied methods in the evaluation of
      health information systems].
AB  - In Brazil, quality monitoring of data from the various health information systems
      does not follow a regular evaluation plan. This paper reviews quality evaluation
      initiatives related to the Brazilian information systems, identifying the
      selected quality dimensions and the method employed. The SciELO and LILACS
      databases were searched, as were the bibliographical references from articles
      identified in the search. 375 articles were initially identified, leaving a final
      total of 78 after exclusions. The four most frequent dimensions in articles
      totaled approximately 90% of the analyses. The studies prioritized certain
      quality dimensions: reliability, validity, coverage, and completeness. Half of
      the studies were limited to data from Rio de Janeiro and Sao Paulo. The limited
      number of studies on some systems and their unequal distribution between regions
      of the country hinder a comprehensive quality assessment of Brazil's health
      information systems. The importance of accurate information highlights the need
      to implement a data management policy for health information systems in Brazil.

PMID- 19851612
TI  - Does the way I see you affect the way I see myself? Associations between
      interviewers' and interviewees' 'color/race' in southern Brazil.
AB  - This study assessed the associations between female interviewers' self-classified
      'color/race' and participants' self- and interviewer-classified 'color/race'. A
      cross-sectional study was carried out among adult individuals living in Pelotas,
      southern Brazil. Associations were examined by means of contingency tables and
      multinomial regression models, adjusting for interviewees' socioeconomic and
      demographic factors. Individuals aged > or = 40 years were 2.1 times more likely
      to classify themselves as brown (versus white) when interviewed by black (as
      compared to white) interviewers. Participants in the same age group were 2.5
      times less likely to classify themselves as black (versus white), when
      interviewed by black interviewers. These differences were even greater among men
      40 years or older. Compared to white interviewers, black female interviewers were
      2.5 times less likely to classify men aged > or = 40 years as black. These
      results highlight the complexity of racial classification, indicating the
      influence of the interviewer's physical characteristics on the interviewee's
      'color/race'.

PMID- 19851613
TI  - [Risk factors for pre-term birth in Londrina, Parana State, Brazil].
AB  - The objective of this study was to identify risk factors associated with pre-term
      birth among live births in a hospital in Londrina, Parana State, Brazil. Cases
      consisted of 328 pre-term births, and controls were 369 births with gestational
      age greater than 37 weeks. A multiple hierarchical logistic regression analysis
      was carried out. There was a significant correlation (p < 0.05) between pre-term
      birth and the following variables: socioeconomic status (slum residence); low age
      of head-of-family; maternal BMI < 19 or > 30 kg/m2; history of prematurity;
      history of assisted reproduction; mothers in a relationship for less than two
      years; maternal stress; weekly maternal alcohol consumption; insufficient
      prenatal care; gestational complications such as bleeding, genital tract
      infection, altered amniotic fluid volume, high blood pressure, and hospital
      admission; and twin pregnancy. Regular walks during pregnancy were a protective
      factor. Improved quality of prenatal care and the identification of the above
      factors during pregnancy may help reduce premature birth.

PMID- 19851614
TI  - [Association between stages of behavior change related to physical activity and
      nutritional status in university students].
AB  - This study aimed to verify the association between stages of behavior change
      related to physical activity and nutritional status among 862 university
      students. Body mass index cut-off values were used to classify nutritional
      status. Stages of behavior change were analyzed individually and classified into
      active (action, maintenance) and inactive (pre-contemplation, contemplation,
      preparation). The most prevalent stages of behavior change were contemplation
      (32%) and preparation (29.5%). Among the entire sample of students, 68.4% were
      inactive. Prevalence rates for underweight, overweight, and obesity were 9.5%,
      12.4%, and 1.7%, respectively. Students classified in the pre-contemplation stage
      were 5.99 times (CI95%: 2.29-15.68) and 7.98 times (CI95%: 1.41-45.32) more
      likely to be underweight and overweight, respectively. The university plays a
      fundamental role in adopting plans and actions targeting the academic community,
      promoting lifestyle changes through physical activity programs.

PMID- 19851615
TI  - [Availability of generic drugs in the public sector and prices in the private
      sector in different regions of Brazil].
AB  - A study to identify availability and prices of medicines, according to type of
      provider, was conducted in the five regions of Brazil. A list of medicines to
      treat prevalent diseases was investigated, using the medicines price methodology
      developed by the World Health Organization and Health Action International,
      adapted for Brazil. In the public sector, bioequivalent (vis-a-vis reference
      brand) generics are less available than multisource products. For most medicines
      (71.4%), the availability of bioequivalent generics was less than 10%. In the
      private sector, the average number of different bioequivalent generic versions in
      the outlets was far smaller than the number of versions on the market. There was
      a positive correlation between the number of generics on the market, or those
      found at outlets, and the price variation in bioequivalent generic products, in
      relation to the maximum consumer price. It is estimated that price competition is
      occurring among bioequivalent generic drugs and between them and multisource
      products for the same substance, but not with reference brands.

PMID- 19851616
TI  - Health related quality of life among the elderly: a population-based study using
      SF-36 survey.
AB  - As life expectancy continues to rise, one of the greatest challenges of public
      health is to improve the quality of later years of life. The aim of this present
      study was to analyze the quality of life profile of the elderly across different
      demographic and socioeconomic factors. A cross-sectional study was carried out in
      two stages, involving 1,958 individuals aged 60 years or more. Health related
      quality of life (HRQOL) was assessed using the SF-36 questionnaire. The lowest
      scores were found among measures for vitality, mental health and general health
      and the highest among factors including social functioning and role limitations
      due to emotional and physical factors. HRQOL was found to be worse among women,
      in individuals at advanced ages, those who practiced evangelical religions and
      those with lower levels of income and schooling. The greatest differences in SF
      36 scores between the categories were observed in functional capacity and
      physical factors. The results suggest that healthcare programs for the elderly
      should take into account the multi-dimensionality of health and social
      inequalities so that interventions can target the most affected elements of HRQOL
      as well as the most vulnerable subgroups of the population.

PMID- 19851617
TI  - [Sick leave among employees of the Sao Paulo State Health Department, Brazil,
      2004].
AB  - Workers' illness and the resulting absenteeism is a relevant issue for the public
      sector, due to the high sick leave rates. The current study focused on the
      characteristics of sick leaves among employees of the Sao Paulo State Health
      Department in Brazil. Data from 2004 were collected for 58,196 public employees
      of the State Health Department, including the respective episodes of sick leave.
      The overall absenteeism rate due to illness was 2.8%, with differences between
      the Department's various divisions and job descriptions. The highest absenteeism
      rates were among hospital workers in operational (3.4%) and patient care jobs
      (3.3%). Total number of sick leave days per worker was associated with job, age
      bracket, and gender. The findings highlight the need to establish policies to
      influence work organization with innovative interventions in the various work
      areas.

PMID- 19851618
TI  - Cross-cultural adaptation, validation and reliability of the Body Area Scale for
      Brazilian adolescents.
AB  - The aim of this study was to translate, validate and verify the reliability of
      the Body Area Scale (BAS). Participants were 386 teenagers, enrolled in a private
      school. Translation into Portuguese was conducted. The instrument was evaluated
      for internal consistency and construct validation analysis. Reproducibility was
      evaluated using the Wilcoxon test and the coefficient of interclass correlation.
      The BAS demonstrated good values for internal consistency (0.90 and 0.88) and was
      able to discriminate boys and girls according to nutritional state (p = 0.020 and
      p = 0.026, respectively). BAS scores correlated with adolescents' BMI (r = 0.14,
      p = 0.055; r = 0.23, p = 0.001) and WC (r =0.13, p = 0.083; r = 0.22, 0.002).
      Reliability was confirmed by the coefficient of inter-class correlation (0.35, p
      < 0.001; 0.60, p < 0.001) for boys and girls, respectively. The instrument
      performed well in terms of understanding and time of completion. BAS was
      successfully translated into Portuguese and presented good validity when applied
      to adolescents.

PMID- 19851619
TI  - [Factors associated with physical activity, sedentary behavior, and participation
      in physical education among high school students in Santa Catarina State,
      Brazil].
AB  - The objectives of this study were to estimate the prevalence of insufficient
      physical activity, sedentary behavior, and absence from physical education and
      associated factors. The Santa Catarina State Adolescents' Questionnaire (COMPAC,
      in Portuguese) was applied to a sample of 5,028 adolescents (15-19 years of age)
      attending public high schools in the State of Santa Catarina, Brazil. Information
      included demographic and socioeconomic indicators. Poisson regression analyses
      were used to test associations. The proportion of students with insufficient
      physical activity was 28.5%, associated with low consumption of fruits and
      vegetables (PR = 1.27; 95%CI: 1.15; 1.40) and enrollment in night classes (PR =
      1.44; 95%CI: 1.34; 1.54). Absence from physical education was reported by 48.6%;
      employment and older age were negatively associated with absence from physical
      education. Sedentary behavior was reported by 38.4%, but was less frequent in
      rural areas (PR = 0.52; 95%CI: 0.31; 0.83) and among those enrolled in absence
      from physical education (RP = 0.73; 95%CI: 0.56; 0.95). The results suggest
      interventions with specific strategies aimed at ameliorating each contributing
      factor.

PMID- 19851620
TI  - [A framework for health surveillance decentralization].
AB  - No consensus has been reached concerning the definition of criteria and standards
      for evaluating the decentralization of actions by municipal health surveillance
      systems. With the aim of developing and validating an objective image for
      municipal health surveillance that would correspond to an appropriate system for
      the population's health care needs, a logical framework was elaborated, from
      which a matrix containing dimensions and criteria for management and practices
      was obtained. The framework was submitted to an expert group for validation at a
      consensus conference. Of the 54 criteria, there was consensus for 59.3%, while 53
      items (98%) were considered important, thus validating the matrix. In view of the
      provisory nature of the consensuses, the resulting instrument, which can be used
      either in its entirety or in part, enables modification and adaptation. The
      authors discuss the potential of the evaluation strategy adopted here, which
      allows various possibilities for redefining the criteria and renewing the
      consensus.

PMID- 19851621
TI  - [Accuracy of the Mortality Information System team in the specification of
      underlying cause of death in a State capital in southern Brazil].
AB  - This cross-sectional study aimed to investigate the quality of data on underlying
      cause of death as completed on the death certificate by the attending physician,
      as well as the accuracy of the Mortality Information System (MIS) team in Porto
      Alegre, Rio Grande do Sul State, Brazil, in specification of the cause. 950
      hospital deaths were investigated, using systematic sampling. A new death
      certificate (DC) was completed with data collected from hospital files, and was
      compared to the original DC and the MIS DC for underlying cause of death.
      Disagreement between the original DC and new DC occurred in 16.1% of cases. Of
      the 103 original DCs containing errors, the MIS identified 64.1%. Among those
      correctly completed, 195 were identified by the MIS as containing problems. Among
      the 261 selected and investigated by the MIS, there was agreement in modification
      of the underlying cause of death between the MIS and the search in 76.8% of
      cases, and a loss of opportunity for qualification in 23.2%. Among the 198 non
      modified DCs, 5.1% should have been modified, and 94.9% were correctly
      maintained. The sensitivity of the MIS in the identification of problems with
      underlying cause of death was 64.1%, and specificity was 75.5%.

PMID- 19851622
TI  - Interactions between antidepressants and antihypertensive and glucose lowering
      drugs among patients in the HIPERDIA Program, Coronel Fabriciano, Minas Gerais
      State, Brazil.
AB  - The aims of this study were to investigate the prevalence and to describe the
      most frequent potential interactions between antidepressants and antihypertensive
      and glucose lowering drugs in the HIPERDIA Program at two primary care units in
      Coronel Fabriciano, Minas Gerais State, Brazil. Data were collected through the
      patient registry in the HIPERDIA Program and the local psychoactive drug
      dispensing system. Interactions were classified as due to pharmacokinetic and/or
      pharmacodynamic mechanisms. Prevalence of antidepressant use in the HIPERDIA
      Program was 4.37% (29 of patient 663 records). Of the HIPERDIA patients in
      treatment with antidepressants, 19 were exposed to 47 interactions, 23.4% of
      which involving pharmacokinetic, 61.7% pharmacodynamic synergy, and 15.9%
      simultaneous pharmacokinetic and pharmacodynamic mechanisms. Complications can
      arise from drug-drug interactions, a situation that can escape the attention of
      prescribing health professionals.

PMID- 19851623
TI  - [Health financing conditions in large cities in Brazil].
AB  - We evaluated the funding of the Brazilian Unified National Health System (SUS) in
      municipalities with more than 100,000 inhabitants. The main goal was to evaluate
      the impact of policies for health resource allocation within the municipal
      budget. A database was organized with information from revenues reported by
      municipalities in the Information System on Government Health Budgets (SIOPS) for
      the year 2005. Reported budgets were compared and correlated to the
      municipalities' geographic location. We conducted a cluster analysis to create
      more homogeneous groups according to health-related budget. The study showed a
      major variability among different regions and States, with varying degrees of
      municipal dependence on external funds. Although the large variability in sources
      may indicate multiple strategies for ensuring the necessary budget funds, the
      study suggests some barriers to public health funding in larger municipalities.

PMID- 19851624
TI  - Frequency of fiber-rich food intake and associated factors in a Southern
      Brazilian population.
AB  - The objective of this study was to verify the frequency of fiber-rich food intake
      and evaluate its association with socioeconomic, demographic and behavioral
      characteristics. A city representative sample was selected and 3,993 subjects (>
      or =10 years) were interviewed. The study used the Block Screening Questionnaire.
      A majority of subjects - 65.6% (95%CI: 64.2-67.1)--presented an inadequate intake
      frequency. Adjusted analysis for the overall sample showed an increased risk of
      inadequate frequency among men, adolescents, people of lower socioeconomic
      levels, current smokers, those insufficiently active and those having fewer than
      four daily meals. Age group-stratified analysis showed that among adolescents,
      living alone was a risk factor; for adults, risk factors were sex (male), current
      smoker, insufficiently active and fewer than four daily meals and; among the
      elderly they were male and being a current smoker. A lower socioeconomic level
      was associated to the outcome in all groups. Although the inadequate frequency of
      intake is very common in this population, teenagers are at a higher risk,
      pointing to a need for public health actions targeting this particular age group.

PMID- 19851625
TI  - [Shortage of ocular health care in the public system: a population-based study].
AB  - This cross-sectional population-based study investigated the prevalence of eye
      care services utilization and the association with socioeconomic and demographic
      factors, need for health care, and type of service payment. The study evaluated
      2,960 adults aged 20 and older. In the previous 5 years, 46% of the sample and
      30% of those aged 50 and older had not visited an eye care service. Among the
      persons who used a service, 18% went to an optical store and only 17% used the
      public health system. The main reason for using eye care services was poor vision
      (69.5%). Lack of money (29%) and time (24.6%) were the most frequently cited
      reasons for non-utilization. Age, education, and economic status were directly
      associated with the outcome. Female gender, cataract, glaucoma, prescription
      eyewear, and private appointments were also associated with the outcome. It is
      necessary to increase the public health system's role, integrating ocular health
      with all levels of health care, expanding participation by other health
      professionals, and intensifying screening and prevention of eye problems.

PMID- 19851626
TI  - Antiretroviral manufacturers and the challenge of universal access to drugs
      through the Brazilian National STD/AIDS Program.
AB  - This article describes the antiretroviral (ARV) manufacturing market in Brazil
      and contextualizes the challenges for the public policy of supplying ARVs through
      the National STD/AIDS Program. Increasing expenditure on these drugs is the main
      source of uncertainty for the policy's future. Brazil's domestic scenario is one
      of growing external dependence, both for the finished drugs and the active
      ingredients. Experience in the National Program has shown that it is the state's
      role to provide public goods, which presupposes ensuring mutual compatibility
      between company interests and social interests. This balance is currently at
      stake in Brazil, since structural changes in the market have raised challenges
      for the National Program's sustainability, requiring new public policy
      instruments in defense of the collective interest. The article drew on a
      literature review, using bibliographic indexing sources, systematic organization
      of primary data, government publications, relevant legislation, research reports,
      and articles recommended by experts from the field.

PMID- 19851627
TI  - Correspondence between children's nutritional status and mothers' perceptions: a
      population-based study.
AB  - This study aimed to investigate the correspondence between the nutritional status
      of children aged 7-10 years and their mothers' perceptions of their children's
      weight. A cross-sectional survey was conducted among 1,282 children. Weight and
      height were measured and classified according to International Obesity Taskforce
      (IOTF) criteria. Mothers' perceptions were assessed based on four possible
      conditions. The Kappa test (k) was used to evaluate the correspondence between
      nutritional status and mothers' perceptions and followed by regression analyses.
      The prevalence of overweight and underweight was 23.2% and 5.7% respectively.
      Half of mothers reported that their children were 'underweight'; 61.2% said that
      their children were 'normal'; 11.8% said that their children were 'above normal
      weight'; and 1.1% referred to their offspring as 'very much above normal weight'.
      Highest and lowest correspondence between nutritional status and mother s
      perception were: underweight and much above normal weight, respectively (k =
      0.217, p < 0.000). Gender and ethnicity showed significant association with the
      mother's perception, even after controlling for other variables. Low
      correspondence levels between nutritional status and mother's perception were
      observed, especially among obese children.

PMID- 19851628
TI  - Etiology of cutaneous leishmaniasis and anthropophilic vectors in Juruti, Para
      State, Brazil.
AB  - In a preliminary study in Juruti, a mining municipality in western Para State,
      Brazil, 12 out of 21 patients suspected of presenting cutaneous leishmaniasis
      showed positive PCR (SSUrDNA and G6PD): Leishmania (Viannia) braziliensis (9/12;
      75%) and L. (V.) sp. (3/12; 25%). Entomological studies in the same location
      revealed the presence of 12 different phlebotomine species (n =105). One of the
      most common species was Lutzomyia (Psychodopygus) complexa (17%) which is both
      highly anthropophilic and a known vector of L. (V.) braziliensis in other regions
      of Para. These preliminary findings should serve to guide future epidemiological
      surveillance in Juruti.

PMID- 19851629
TI  - [Epidemic of risk behaviors? A note on unequal socio-cultural contexts and
      subjective dimensions of the health-disease process].

PMID- 19851631
TI  - Drug use and associated factors in children living in poor areas.
AB  - OBJECTIVE: To describe drug use profile in children living in poor areas and
      associated factors. METHODS: Population-based, cross-sectional study, including
      1,382 children aged between four and 11 years. These children were selected by
      random sampling of 24 micro-areas, representative of the poorest segments of the
      population living in the city of Salvador, Northeastern Brazil, in 2006. The
      dependent variable was drug use in the 15 days preceding the surveys. A total of
      three groups of explanatory variables were considered: socioeconomic variables,
      child health status, and use of health services. Adjusted analysis used Poisson
      regression, following a hierarchical conceptual model. RESULTS: Drug use
      prevalence in children was 48%. Female children showed higher drug use prevalence
      than males, 50.9% and 45.4%, respectively (p=0.004). Drug use prevalence
      decreased significantly with age (p<0.001) in both sexes. Most used
      pharmacological groups were: analgesics/antipyretics (25.5%), systemic
      antibiotics (6.5%), and anti-cough /expectorant drugs (6.2%). In the multivariate
      analysis, factors determining greater drug use were: age (four to five, six,
      seven to eight years); female sex; white mother; poorer health perception;
      interruption of activities due to health problems and health care, whether ill or
      not, in the last 15 days; drug spending in the last month; and medical visits in
      the last three months. CONCLUSIONS: Drug use prevalence in the poor children
      studied was below that observed in other population-based studies in Brazil, yet
      similar to that of adults. The identification of groups most subject to excessive
      drug use may serve as the basis for strategies to promote their rational use.

PMID- 19851630
TI  - Homicide and impunity: an ecological analysis at state level in Brazil.
AB  - OBJECTIVE: To assess a new impunity index and variables that have been found to
      predict variation in homicide rates in other geographical levels as predictive of
      state-level homicide rates in Brazil. METHODS: This was a cross-sectional
      ecological study. Data from the mortality information system relating to the 27
      Brazilian states for the years 1996 to 2005 were analyzed. The outcome variables
      were taken to be homicide victim rates in 2005, for the entire population and for
      men aged 20-29 years. Measurements of economic and social development, economic
      inequality, demographic structure and life expectancy were analyzed as
      predictors. An 'impunity index', calculated as the total number of homicides
      between 1996 and 2005 divided by the number of individuals in prison in 2007, was
      constructed. The data were analyzed by means of simple linear regression and
      negative binomial regression. RESULTS: In 2005, state-level crude total homicide
      rates ranged from 11 to 51 per 100,000; for young men, they ranged from 39 to
      241. The impunity index ranged from 0.4 to 3.5 and was the most important
      predictor of this variability. From negative binomial regression, it was
      estimated that the homicide victim rate among young males increased by 50% for
      every increase of one point in this ratio. CONCLUSIONS: Classic predictive
      factors were not associated with homicides in this analysis of state-level
      variation in Brazil. However, the impunity index indicated that the greater the
      impunity, the higher the homicide rate.

PMID- 19851632
TI  - Effectiveness of see-and-treat for approaching pre-invasive lesions of uterine
      cervix.
AB  - OBJECTIVE: To compare the effectiveness between the see-and-treat (S&T) approach
      and the conventional one (with prior biopsy) for squamous intraepithelial lesions
      of uterine cervix. METHODS: A cross-sectional study was conducted with 900
      nonpregnant women with cytology suggestive of high grade squamous intraepithelial
      lesions in the city of Rio de Janeiro, Southeastern Brazil, between 1998 and
      2004. The S&T approach consists of a large loop excision of the transformation
      zone procedure and is recommended when cytology is suggestive of high grade
      squamous intraepithelial lesion, satisfactory colposcopy with abnormalities
      compatible with the suspected cytological results, and the lesion is limited to
      the ectocervix or extends up to one centimeter of the endocervical canal. A
      subgroup of 336 patients whose colposcopy was considered satisfactory was
      analyzed, and they were divided into two groups for comparison: patients treated
      without prior biopsy (n = 288) and patients treated after a biopsy showing high
      grade squamous intraepithelial lesions (n = 48). Patients who were not treated or
      only treated more than a year later after recruitment at the colposcopy unit were
      considered dropouts. RESULTS: Of patients recruited during the study period, 71
      were not treated or were only treated for at least a year. The overall dropout
      rate was 7.9% (95% CI: 6.1;9.7). Mean time elapsed between patient recruitment
      and treatment was 17.5 days in the S&T group and 102.5 days in the prior biopsy
      group. Dropout rates were 1.4% (95% CI: 0.04;2.7) and 5.% (95% CI: 0;12.3),
      respectively (p=0.07). The proportion of overtreated cases (negative histology)
      in the S&T group was 2.0% (95% CI: 0.4;3.6). CONCLUSIONS: The difference in the
      mean time elapsed between patient recruitment and treatment indicates that S&T is
      a time-saving approach The proportion of negative cases from using the S&T
      approach can be regarded as low.

PMID- 19851633
TI  - Malaria vectors in two indigenous reserves of the Brazilian Amazon.
AB  - OBJECTIVE: To describe the composition, ecological and behavioral characteristics
      and infectivity of Anopheles species in indigenous reserves of the Amazon region.
      METHODS: The study was performed in villages of the Nhamunda-Mapuera and
      Cuminapanema indigenous reserves, in the state of Para, Northern Brazil, in 2002.
      A total of three two-week collections were conducted in each reserve, with the
      capture of adult and immature forms. Adult Anopheles specimens were captured
      using a Castro sucking tube with human landing trap in indoor and outdoor
      environments, from 6.00 pm to 9.00 pm and from 6.00 pm to 6.00 am, and
      subsequently assessed to verify parity and infectivity by plasmodiums using
      dissection and ELISA. Water collections near the villages were surveyed using 500
      ml ladles, with 20 ladlefuls for each 10 m, covering the maximum extent of 200 m
      of perimeter around the breeding spot. RESULTS: Adding up the collections from
      both reserves, a total of 8,668 females were captured. Anopheles darlingi was the
      most frequent species, with higher frequency around the homes. In the Mapuera
      reserve, blood feeding activity was concentrated between 8.00 pm and 12.00 am,
      while, in Cuminapanema, it remained high until 12.00 am, decreasing after this
      time and increasing again early in the morning. Of all the 6,350 An. darlingi
      females analyzed, 18 were infected with Plasmodium vivax VK247, VK210, P.
      falciparum and P. malariae. In addition, other 1,450 females of other species
      were analyzed, but none was found infected. An. nuneztovari and Chagasia bonnae
      were the most frequent species in the breeding spots of the Mapuera and
      Cuminapanema villages, respectively. Immature An. darlingi forms were not located
      in Mapuera and were captured in only one of the collections of the Cuminapanema
      reserve. CONCLUSIONS: An. darlingi populations in the two reserves showed
      exophilic behavior and intense nocturnal activity. The occurrence of immature
      forms was little frequent and larval density was low. Vector behavioral
      characteristics were not favorable for the usual vector control activities.

PMID- 19851634
TI  - Job strain and hypertension in women: Estudo Pro-Saude (Pro-Health Study).
AB  - This study aimed to analyze the association between job strain and hypertension
      in the female population. A cross-sectional study was performed with 1,819 women
      who participated in the Estudo Pro-Saude (Pro-Health Study), in the city of Rio
      de Janeiro, Southeastern Brazil, between 1999 and 2001. The Brazilian version of
      the short version of the Job Stress Scale (demand-control model) was used.
      Overall prevalence of measured hypertension (> or =140/90 mmHg and/or
      antihypertensive drug use) was 24%. Compared to participants with jobs classified
      as low strain, adjusted prevalence ratios for hypertension in women who performed
      passive and active high-strain jobs were, respectively, 0.93 (95% CI: 0.72;1.20),
      1.06 (95% CI: 0.86;1.32) and 1.14 (95% CI: 0.88;1.47). Longitudinal analyses
      should be performed to clarify the role of these work environment psychosocial
      characteristics as a determinant of hypertension.

PMID- 19851635
TI  - Dengue prevention at the household level: preliminary evaluation of a mesh cover
      for flowerpot saucers.
AB  - The effectiveness of a polyester mesh cover (evidengue), aimed at preventing the
      access of female Aedes aegypti mosquitoes to flowerpot saucers, was evaluated in
      laboratory. Two saucers of flowerpot with water were individually wrapped with
      the cover was placed with their respective pots in two entomological cages. One
      identical set of flowerpot and saucer was placed in a third cage. In each cage,
      20 gravid females, fed on mouse blood, were released. Results show that the cover
      was effective to prevent access of females. Further tests are necessary to assess
      cover effectiveness as a device to prevent saucer oviposition.

PMID- 19851636
TI  - [National guidelines for research involving human tissue repositories and
      biobanks].

PMID- 19851637
TI  - [Characteristics of Influenza A(H1N1) notified cases].

PMID- 19851639
TI  - TG-ROC analysis of immunofluorescence assays in canine visceral leishmaniasis
      diagnosis.
AB  - OBJECTIVE: To analyze the accuracy of the diagnosis of two protocols of indirect
      immunofluorescence assays for canine visceral leishmaniasis. METHODS: Dogs from
      the seroepidemiological survey conducted in an endemic area of the cities of
      Aracatuba and Andradina, in Northwestern Sao Paulo state, in 2003, and in a non
      endemic area of the metropolitan region of Sao Paulo, were used to assess two
      protocols of indirect immunofluorescence assay (IFA) for leishmaniasis: one using
      a Leishmania major heterologous antigen (IFA-BM) and another using a Leishmania
      chagasi homologous antigen (IFA-CH). Two-graph receiver operating characteristic
      (TG-ROC) analysis was used to estimate accuracy. TG-ROC analysis compared 1:20
      dilution readings of the homologous antigen (IFA-CH), considered as reference
      test, with IFA-BM dilutions (heterologous antigen). RESULTS: The 1:20 dilution
      used in the IFA-CH test showed the best contingency coefficient (0.755) and the
      highest strength of association between the two variables studied (chi
      square=124.3). Thus, it was considered the test reference dilution in comparisons
      with different IFA-BM test dilutions. The best IFA-BM results were obtained from
      1:40 dilutions with the best contingency coefficient (0.680) and highest strength
      of association (chi-square=80.8). With the change in the cut-off point,
      recommended for the IFA-BM 1:40 dilution in this analysis, the specificity
      parameter value rose from 57.5% to 97.7%, even though the 1:80 dilution showed
      the best sensitivity estimate (80.2%), with the new cut-off point. CONCLUSIONS:
      TG-ROC analysis can provide important information about diagnostic tests, in
      addition to offering suggestions on cut-off points that can improve test
      sensitivity and specificity estimates and assessing these tests in terms of the
      best cost-benefit ratio.

PMID- 19851640
TI  - Coronary artery bypass using only computed tomography as pre-operative angiogram.
AB  - Coronary artery bypass graft (CABG) is a well established procedure with current
      precise indications. The advent and spread of this technique was possible after
      the introduction of the coronary angiogram. Although many evaluation methods have
      been developed in the past years, to date, none have been able to replace the
      invasive coronary angiogram as a pre-operative exam. Computed tomography
      angiography (CTA) has emerged as an alternative to invasive coronary angiogram.
      In this report we describe two CABG cases that were performed using only this
      technique as a pre-operative anatomic coronary arteries evaluation.

PMID- 19851641
TI  - Large bilateral coronary artery fistula: the choice of clinical treatment.
AB  - We report the case of an asymptomatic female patient, with a large non
      complicated bilateral coronary-pulmonary artery fistula. Clinical monitoring was
      the choice of treatment. We discuss the therapeutic options in depth, emphasizing
      the excessive tendency of the surgical approach and the great scarcity of reports
      on long-term clinical follow-up in asymptomatic patients.

PMID- 19851642
TI  - Myocardial homing after intrapericardial infusion of bone marrow mononuclear
      cells.

PMID- 19851643
TI  - Gender, age, social level and cardiovascular risk factors: considerations on the
      Brazilian reality.

PMID- 19851644
TI  - Mechanical prosthetic valve thrombosis.

PMID- 19851646
TI  - Ibero-American cardiovascular magazines: proposals for a necessary collaboration.

PMID- 19851647
TI  - Children with adult hearts.

PMID- 19851648
TI  - Reversal atrial electrical remodeling following cardioversion of long-standing
      lone atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) itself promotes electrophysiological
      changes, termed 'electrical remodeling', facilitating its recurrence and
      maintenance. There is evidence that the remodeling process is reversible after
      restoration of the sinus rhythm (SR). However, the timing for the recovery of
      electrophysiological properties is still undefined. OBJECTIVE: The aim of this
      study was to assess the atrial electrical activation using P-wave signal-averaged
      electrocardiogram (P-SAECG) post-cardioversion of long-standing AF, focusing on
      the reversal remodeling process to identify the timing of the process
      stabilization. METHODS: Subjects with lone persistent AF, eligible for
      cardioversion and successfully converted to SR, were enrolled at the study. SAECG
      was performed immediately after reversion to SR and repeated on days seven and
      thirty. RESULTS: Of 31 subjects, nine presented early recurrence of atrial
      fibrillation, all of them in the first seven days post-cardioversion; 22 remained
      in SR for at last one month and SAECG was obtained on days seven and thirty after
      cardioversion. In the latter, P-wave duration progressively abated from the first
      to the third SAECG (P-wave duration: 185.5+/-41.9 ms vs 171.7+/-40.5 ms vs
      156.7+/-34.9 ms, respectively, first, second and third SAECG; p<0.001 for all
      matches). In the frequency domain analysis, spectral turbulence was not apparent
      in SAECG immediately post-cardioversion, but sharply increased on day seven and
      remained unchanged on day thirty. CONCLUSION: This study suggests that the first
      seven days post-cardioversion of long standing AF are critical for reversal
      remodeling process and arrhythmia recurrence.

PMID- 19851649
TI  - Severity of angiographic coronary obstruction and the apolipoprotein E
      polymorphism in acute coronary syndromes.
AB  - BACKGROUND: There is evidence of the association between the apolipoprotein E
      (APOE) and coronary disease; however, there are controversies. OBJECTIVE: To
      evaluate the association between the number of coronary vessels with significant
      obstruction defined by angiography, the APOE polymorphism and clinical variables.
      METHODS: This was a cross-sectional, multicenter study with 207 patients (138
      men), with acute coronary syndrome (ACS), in the city of Niteroi, state of Rio de
      Janeiro, Brazil, who underwent coronary angiography and genotype determination
      for the APOE *2*3*4 polymorphism by the Restriction Fragment Length Polymorphism
      (RFLP) method. RESULTS: The frequency of the alleles was APOE *2 - 6.8%, *3 -
      82.5%, *4 - 10.7%. Regarding the number of affected vessels, 27% of patients
      presented monoarterial obstruction, 33.8% biarterial and 39.1% triarterial and/or
      left coronary trunk. The degree of multivascular lesion did not correlate with
      the presence of the *4 allele (p= 0.78), but with age > 55 years (p=0.025), being
      an ex-smoker (p=0.004) and dyslipidemia (p=0.05) at the multivariate analysis and
      also with previous coronary artery disease (CAD) (p=0.05), diabetes (p=0.038) and
      metabolic syndrome (p=0.021) at the univariate analysis. The prevalence of
      dyslipidemia, diabetes and systemic arterial hypertension (SAH) was elevated
      regarding similar studies, with progressive increases in the prevalence of SAH
      (p=0.59) and diabetes (p=0.06), according to the number of affected vessels.
      CONCLUSION: The APOE polymorphism was not associated with the number of coronary
      vessels with significant obstruction at any age range. On the other hand, age >
      55 years, being an ex-smoker and dyslipidemia associated with the multivascular
      lesion.

PMID- 19851650
TI  - Importance of HDL-c for the occurrence of cardiovascular disease in the elderly.
AB  - BACKGROUND: Studies on the impact of HDL-c and the occurrence of cardiovascular
      disease (CV) in the elderly are scarce. OBJECTIVE: To evaluate the clinical and
      laboratory variables and the occurrence of CV events in elderly patients
      stratified according to the behavior of HDL-c during an eight-year follow up.
      METHODS: We evaluated 81 elderly patients, mean age of 68.51 +/- 6.32 years
      (38.2% male), in two stages (A1 and A2), with a minimum interval of five years.
      The subjects were divided into 3 groups according to HDL-c levels: normal HDL-c
      in both assessments (NG) (n = 31), low HDL-c in both assessments (LG) (n = 21)
      and variable HDL-c in A1 and A2 (VG) (n = 29). Main CV events were recorded:
      coronary heart disease (angina, myocardial infarction, percutaneous / surgical
      myocardial revascularization), stroke, transient ischemic attack, carotid
      disease, dementia and heart failure. RESULTS: The groups did not differ in gender
      and age in A1 and A2. Mean triglyceride levels were lower in the NG in A1 (p =
      0.027) and A2 (p = 0.016) than in the LG. The distribution of CV events was as
      follows: 13 events in the NG (41.9%), 16 (76.2%) in the LG, and 12 (41.4%) in the
      VG (chi2 = 7.149, p = 0.024). The logistic regression analysis showed that the
      older the patient (OR = 1.187, p = 0.0230) and the lower the HDL-c (OR = 0.9372,
      p = 0.0102), the greater the occurrence of events CV. CONCLUSION: Permanently low
      HDL-c during eight years of monitoring is a risk factor for the development of CV
      events in the elderly.

PMID- 19851651
TI  - Heart rate variability, blood lipids and physical capacity of obese and non-obese
      children.
AB  - BACKGROUND: Obesity can affect the cardiac autonomic modulation, blood lipid
      levels and the physical capacity. OBJECTIVE: To study the effect of obesity on
      the heart rate variability (HRV), blood lipid levels and physical capacity of
      obese children. METHODS: Thirty children aged 9 to 11 years were studied, divided
      in two groups: a) 15 obese children (O) aged 10.2 +/- 0.7 years and body mass
      index (BMI) between the 95th and the 97th percentiles; b) 15 non-obese children
      (NO) aged 9.8 +/- 0.7 years and BMI between the 5th and 85th percentiles. All
      children were submitted to an anthropometric and clinical assessment, analysis of
      the HRV at rest and a physical exercise protocol (PEP). Non-parametric tests were
      used to compare the variables between the groups. The level of significance was
      set at p < 0.05. RESULTS: The waist circumference and levels of triglycerides
      were higher in O. The cardiac sympathetic activity in the standing position in
      normalized units (LF n.u.) was higher in O, 71.4%, when compared to NO, 56.3%.
      The low frequency/high frequency ratio (LF/HF) was 3.8 in O and 1.7 in NO. The
      PEP showed differences between the groups, with higher values observed in NO
      children regarding the total distance, time of exposure to PEP, peak oxygen
      consumption (VO2 peak) and metabolic equivalent (MET). CONCLUSION: Obesity in
      children resulted in alterations in cardiac autonomic control in the standing
      position and decreased the physical capacity.

PMID- 19851652
TI  - Acute kidney injury after on-pump coronary artery bypass graft surgery.
AB  - BACKGROUND: The acute kidney injury (AKI) is a complex disease for which there is
      no accepted standard definition nowadays. The Acute Kidney Injury Network (AKIN)
      represents an attempt to standardize the criteria for diagnosis and staging of
      acute renal dysfunction based on recently published RIFLE criteria, that means,
      (Risk, Injury, Failure, Loss, and End-stage kidney disease). OBJECTIVES: To
      evaluate the incidence and associated mortality of AKI in patients submitted to
      on-pump coronary artery bypass graft surgery (on-pump CABG). METHODS: A total of
      817 patients were divided into two groups: negative AKI (-), with 421 patients
      (51.5%), and positive AKI (+), with 396 patients (48.5%). Increase of 0.3 mg/dL
      in creatinine or of 50% in creatinine's basal value was considered as AKI.
      RESULTS: The rate of patient's mortality with or without AKI within 30 days after
      cardiac surgery was 12.6% and 1.4%, respectively (p<0.0001). In a multivariate
      logistic regression model, AKI after on-pump CABG was an independent predictor of
      death within 30 days (OR=6.7; p=0.0002). This group of patients presented a
      longer period of permanency in intensive care unit (ICU) [median 2 days (2 to 3)
      versus 3 days (2 to 5); p=0.0001] and a bigger proportion of patients with
      prolonged permanence in intensive care (>14 days) (14 versus 2%; p=0.0001).
      CONCLUSION: In the studied population, even a discrete alteration in renal
      function, based on AKIN criteria, was an independent predictor of death in 30
      days after on-pump CABG.

PMID- 19851653
TI  - Obesity and its association with other cardiovascular risk factors in school
      children in Itapetininga, Brazil.
AB  - BACKGROUND: Paucity of data on childhood obesity and cardiovascular risk in
      Brazil. OBJECTIVE: To determine the prevalence of hypertension, dyslipidemia,
      obesity and their correlations in a sample of school children in Itapetininga,
      State of Sao Paulo, Brazil. METHODS: Cross-sectional study with systematic
      collection of anthropometric data (weight, height, waist circumference, BMI and
      blood pressure levels) and determination of glucose, total cholesterol, LDL, HDL,
      uric acid, and apolipoproteins A and B in a random sample representative of
      school children from the public education system in Itapetininga, State of Sao
      Paulo. For data analysis, we used population parameters from the NCHS curves
      (2000), blood pressure categories from NHBPEP (2004), and the serum cholesterol
      levels proposed by the AHA for children and adolescents (2003). RESULTS: A total
      of 494 children and adolescents participated in the study. Of these, 11.7% had
      HBP, 51% increased total cholesterol, 40.5% increased LDL-cholesterol, 8.5%
      increased triglycerides, and 6.1% low HDL-cholesterol levels. Mean (+/- standard
      deviation) TC, HDL-cholesterol, LDL-cholesterol and triglycerides were
      172.1(27.9), 48.1(10.0), 105.7(23.1) and 90.9(43.8), respectively. Obesity and
      overweight were detected in 12.8% and 9.7% of the sample, respectively.
      Individuals of the obese group had a greater chance of presenting with
      dyslipidemia and hypertension in comparison with those of the other groups.
      CONCLUSION: This study supports the hypothesis of different prevalences of excess
      weight among school children from the public education system of the northeastern
      and southeastern regions of Brazil, with higher rates in the latter.
      Additionally, it demonstrates an association of obesity with dyslipidemia and
      hypertension in that group. In light of the paucity of Brazilian data on this
      issue, our study provides important data for further comparisons.

PMID- 19851655
TI  - Prevalence of anemia and renal insufficiency in non-hospitalized patients with
      heart failure.
AB  - BACKGROUND: Heart Failure (HF) is a common disease with a high rate of mortality.
      Anemia and renal failure (RF) are often found in patients with HF associated with
      higher severity of the heart disease and a worse prognosis. OBJECTIVE: To
      evaluate the prevalence of anemia and RF, as well as the association between
      these two conditions, in non-hospitalized patients with HF. METHODS: Patients
      treated at the HF Outpatient Clinic of a university hospital were followed from
      July 2003 to November 2006. Anemia was defined as hemoglobin levels < 13 mg/dl
      for men and 12 mg/dl for women. Renal function was assessed by the glomerular
      filtration rate (GFR), calculated by the simplified formula of the MDRD
      (Modification of Diet in Renal Disease) study. RESULTS: Of the 345 patients
      included in this study, 26.4% (n = 91) had anemia and 29.6% had moderate to
      severe renal failure (GFR < 60 ml/min). The association between anemia and a
      higher prevalence of renal failure was statistically significant (41.8% vs.
      25.2%; p = 0.005). The patients at functional class III and IV presented a higher
      incidence of anemia (39.0% vs. 19.4%; p <0.001) and renal failure (38.2% vs.
      24.8%; p = 0.007). No association was observed between anemia or renal failure
      and history of hypertension, diabetes, systolic function or etiology of HF.
      CONCLUSION: The prevalence of anemia and renal failure was high in this
      population and was associated with the severity of the HF (functional classes III
      and IV).

PMID- 19851654
TI  - Body mass index has a good correlation with proatherosclerotic profile in
      children and adolescents.
AB  - BACKGROUND: More recently, the association of different risk factors has been
      described as the metabolic syndrome. Different definitions are being used for the
      same syndrome. Regardless of the name or classification, it has been well
      established that a cardiovascular cluster including overweight/obesity, increased
      blood pressure, and lipid and glucose abnormalities are associated with an
      increased risk of atherosclerosis in adults. OBJECTIVE: The aim of this study was
      to correlate body mass index percentiles with blood pressure, insulin resistance
      index, and lipid profiles in children and adolescents, which characterize a
      proatherosclerotic profile. METHODS: Cardiovascular risk factor clusters were
      evaluated in 118 children and adolescents divided according to body mass index
      percentile (BMIP) quartiles: Q1 (n=23) with BMIP <50%, Q2 (n=30) with BMIP
      between 50 and 85%, Q3 (n=31) with BMIP between 85 and 93%, and Q4 (n=34) with
      the BMIP > 93%. Statistically significant differences were not observed for age
      (F=2.1; p=0.10); sex (chi-square test=3.0; p=0.38), and ethnicity (chi-square
      test=4.7; p=0.20) between different quartiles. RESULTS: A statistically
      significant difference was observed for systolic BP (F=15.4; p<0.0001), diastolic
      BP (F=9.5; p<0.0001), glycemia (F=9.6; p<0.0001), insulin (F=12.9; p<0.0001),
      HOMAir (F=30.8; p<0.0001), and triglyceride levels (F=2.7; p=0.05) between the
      different quartiles. CONCLUSION: Excess weight evaluated by BMIP was associated
      with increased blood pressure, triglycerides, HOMAir index, and low HDL
      cholesterol, a proatherosclerotic profile in children and adolescents.

PMID- 19851656
TI  - ABPM in COPD patients with sleep desaturation.
AB  - BACKGROUND: Sleep hypoxemia may change blood pressure by sympathetic activation.
      Few studies have analyzed blood pressure parameters in COPD patients who do not
      present sleep apnea, but do present sleep desaturation. OBJECTIVES: To analyze
      blood pressure parameters in COPD patients with sleep desaturation not caused by
      apnea. METHODS: Thirteen patients with COPD underwent spirometry, blood gas,
      polysomnography and ABPM for blood pressure evaluation. Fourteen patients without
      COPD underwent spirometry, oximetry and ABPM. Blood pressure analyses were
      carried out both during wakefulness and sleep. Both groups were comprised of
      patients with no history of hypertension. RESULTS: The two groups were similar as
      regards age, height, weight, and body mass index. A significant difference
      (p<0.05) was found between blood pressure levels during the wakefulness, sleep,
      24-hour and sleep dip periods. Higher blood pressure levels were observed in
      patients with COPD, except for diastolic levels during wakefulness and maximum
      values during sleep and in the 24 hours. Sleep dip in the COPD group was
      attenuated, whereas physiological dip was observed in the control group, with
      lower blood pressure levels. CONCLUSIONS: Systolic and diastolic blood pressure
      levels in the COPD group were higher than those of the control group, with a
      significant difference found for all periods studied, except for diastolic levels
      during wakefulness and in the 24 hours. We can conclude that the group of COPD
      patients with sleep desaturation has significantly higher blood pressure levels
      than the control group.

PMID- 19851657
TI  - Postoperative outcome of patients with prosthetic valve leak.
AB  - BACKGROUND: Prosthetic valve leak is a possible complication of surgical valve
      replacement. Although uncommon, its consequences may be serious. Few studies
      correlate the degree of prosthetic valve leak with clinical events. OBJECTIVE: To
      compare the postoperative outcome of patients with mild/moderate (Mi/Mo) or
      severe (Sev) prosthetic valve leak METHODS: A total of 185 patients with
      prosthetic valve leak were selected among 1350 patients undergoing heart valve
      surgery between 1999 and 2001. Of these, a sample of 58 patients (37 men) with
      prosthetic valve leak (36 with Mi/Mo versus 22 with Sev leak) in the pre and/or
      postoperative period of heart valve replacement had complete medical record data,
      so their clinical, laboratory and echocardiographic data could be retrospectively
      assessed. RESULTS: The incidence of reoperation was 11.1% in the Mi/Mo group,
      versus 22.7% in the Sev group (odds ratio = 2.35 [95% CI 0.56-9.94]).
      Endocarditis was the cause of reoperation in 75% of the patients of the Mi/Mo
      group and in 60% of the Sev group. Aortic bioprostheses were those most
      frequently related to leak (55.8% in the Mi/Mo group and 57.7% in the Sev group).
      Forty percent of the patients with previous Mi/Mo leak did not present prosthetic
      valve leak on postoperative day 2 versus 21.4% of the patients with Sev
      prosthetic valve leak. No significant differences were found regarding laboratory
      variables. CONCLUSIONS: (1) Patients with severe leak are more likely to undergo
      reoperation. (2) Endocarditis was the most frequent cause of reoperation for any
      leak degree. (3) Severe prosthetic valve leak is more difficult to fully resolve
      after surgical treatment.

PMID- 19851658
TI  - Isolated mitral and aortic valve replacement with the St. Jude Medical valve: a
      midterm follow-up.
AB  - BACKGROUND: In our country, the biological valvular prostheses predominate,
      considering the difficulties related to anticoagulation, even in young patients,
      in spite of the need for repeated operations due to the degeneration of the
      bioprostheses. OBJECTIVES: To report our consecutive series of recipients of
      isolated St Jude Medical mechanical valve prosthesis in the mitral (MVR) or
      aortic (AVR) position. METHODS: Data from patients operated between January 1995
      and December 2003 were revised in order to determine patient survival and
      prosthesis-related events up to December 2006. RESULTS: One hundred sixty eight
      patients had MVR and 117 had AVR. In the MVR cohort, the mean age was 45 years,
      75% were 55 years old or younger, and 65% were females. In the ARV cohort, the
      mean age was 45 years, 66% were 55 years old or younger and 69% were males.
      Operative mortality for AVR and MVR was 7% and 7.5%, respectively. Freedom from
      late mortality was 81.8% at 10 years for MVR and 83% for AVR (p=0.752). Freedom
      from valve-related death at 10 years for the MVR cohort and AVR was 85.6% and
      88.7%, respectively (p=0.698). In the MVR cohort, the freedom from reoperation
      was 97% and 99% in the AVR cohort (p=0.335). Freedom from thromboembolic events
      was 82% in the MVR cohort and 98% in the AVR cohort (p=0.049). Freedom from
      bleeding was 71% in the MVR cohort and 86% n the AVR cohort (0.579). Freedom from
      endocarditis was 98% in the MVR cohort and 99% in the AVR cohort (p=0.534).
      CONCLUSIONS: This series of predominantly young adult patients undergoing
      isolated MVR and AVR with the St Jude Medical mechanical prosthesis confirms the
      good performance of this valve prosthesis in agreement with previous reports.

PMID- 19851659
TI  - Percutaneous aortic valve replacement for the treatment of aortic stenosis: early
      experience in Brazil.
AB  - BACKGROUND: Percutaneous aortic valve replacement for the treatment of aortic
      stenosis is an available and efficient alternative for patients at high surgical
      risk, especially those with advanced age and comorbidities. OBJECTIVE: The
      authors report the first experience made in our midst with the use of the
      CoreValve endoprosthesis. METHODS: In January 2008, two patients underwent
      percutaneous aortic valve replacement due to symptomatic aortic stenosis. They
      were selected for being elderly (77 and 87 years) and presenting comorbidities
      and a high surgical risk (EuroScore 7.7% and 12.1%). RESULTS: Percutaneous
      implantations of the CoreValve device were successfully performed. Enlargement of
      the valve area (from 0.7 to 1.5 cm(2) and from 0.5 to 1.3 cm(2)) and reduction of
      the aortic transvalvular gradient (from 82 to 50 mmHg and from 94 to 31 mmHg)
      were observed immediately after the intervention. During hospital stay, permanent
      pacemaker implantation was required in both patients due to atrioventricular
      block. At six months, an even greater drop in the aortic transvalvular gradient
      (gradient < 20 mmHg) and remission of symptoms of heart failure (NYHA III to NYHA
      I) were observed. CONCLUSION: The use of the CoreValve endoprosthesis for the
      treatment of aortic stenosis proved to be feasible and showed encouraging results
      in this early experience made in our midst.

PMID- 19851661
TI  - Occlusion of the left coronary trunk secondary to tertiary syphilis.
AB  - A 27-year-old patient with tertiary syphilis, manifested as myocardial ischemia,
      presenting unstable angina, secondary to left coronary trunk occlusion. The
      diagnosis was confirmed by the serological findings and the pathological
      assessment of the aorta fragment.

PMID- 19851660
TI  - Joint hypermobility in patients with mitral valve prolapse.
AB  - Studies on hypermobility have aroused great interest in the last decades, as they
      are associated to musculoskeletal disorders, as well as abnormalities in several
      organic systems, such as the mitral valve prolapse. Therefore, in this study,
      data on the association between joint hypermobility and the mitral valve prolapse
      were investigated and reviewed. Studies in the literature have shown that genetic
      alterations in the collagen composition seem to be the main cause of this
      association.

PMID- 19851662
TI  - Case 4/2009--a 55-year-old male patient with Chagas cardiomyopathy who developed
      progressive worsening of dyspnea, chest pain and pulmonary interstitial
      infiltrate.

PMID- 19851663
TI  - [Kawasaki disease].
AB  - Kawasaki disease is a systemic acute vasculitis of unknown etiology. It is the
      leading cause of acquired heart disease in children in the USA. It occurs more
      frequently in boys and eighty percent of the cases occur in children under five
      years of age. The disease rarely occurs after eight years and it can affect
      children of all races, with higher incidence among Asian descendants. Kawasaki
      disease is characterized by fever, bilateral non-exudative conjunctivitis,
      redness and swelling of the tongue, lips and oral mucosa, abnormalities in the
      extremities, cervical lymph node, and polymorphic exanthema. Aneurysms and
      stenoses of coronary arteries occur in approximately 20 to 25% of untreated
      patients and subsequently can lead to acute myocardial infarction and sudden
      death. Treatment with intravenous immunoglobulin is effective and should be
      initiated early to prevent cardiac sequel. The development of diagnostic tests,
      more specific treatment approaches and prevention of this potentially fatal
      disease in children depends on continuous advances in the determination of its
      pathogenesis.

PMID- 19851664
TI  - [Evaluation of the epidemiological profile and the mortality rate of the patients
      with primary cutaneous melanoma in Florianopolis - SC, Brazil].
AB  - BACKGROUND: Melanoma is the cutaneous cancer which has the greatest lethality.
      Santa Catarina is the Brazilian State that contributes the most to increase this
      rate. OBJECTIVES: To estimate the mortality rate of melanoma in the fifth year of
      illness. METHODS: The sample comprises 81 reports of primary cutaneous melanoma,
      in 75 patients, diagnosed in lorianopolis - SC in 2002 and 2003. The protocol of
      research includes age, sex, patient's color, anatomical location, histological
      type, degree of invasion, Breslow index, inflammatory reaction, ulceration,
      regression, angiolymphatic invasion and tumor staging. The patients were
      contacted by telephone to verify their status (alive, killed by melanoma or dead
      for another reason). Fisher's exact test and Kaplan-Meier's survival curve were
      used for the statistical analysis. RESULTS: The patients' profile was: female,
      white, 51.3 years of age, with invasive melanoma on the trunk and limbs,
      extensive spreading type, Breslow 2.63 mm. The mortality rate was 7.0%, greater
      among men (11.1%), Breslow above 4.0 mm (66.0%), with ulceration (33.3%) and
      stage IV (80.0%). The average survival period was 56.7 months. CONCLUSIONS: The
      mortality rate of primary cutaneous melanoma was 7.0%; ulceration and the final
      staging were the factors with statistic significance on the result.

PMID- 19851665
TI  - [Identification of acute diseases caused by animals and plants in wild
      environments: contribution to dermatologic practice].
AB  - BACKGROUND: In recent years, there has been increasing contact between human
      beings that live in urban regions and the wild environment due to a series of
      activities. As a result, some poorly known dermatitis may present in private and
      dermatological clinics, especially early in the week and at the end of vacation
      periods. OBJECTIVES: To obtain and provide information for dermatologists on the
      problem. PATIENTS AND METHODS: The author observed adult and pediatric patients
      with acute dermatitis associated with plants or animals in Ubatuba, coastal city
      of Sao Paulo for 2 months (June / July 2006) and Medical School of Botucatu (June
      / July 2007). RESULTS: We observed 25 patients in the rural area and 43 in the
      coastal environment. In rural areas, the most common dermatitis were
      phytophotodermatitis and the stings of insects and in coastal areas, sea urchin
      injuries and phytophotodermatitis, but in both areas there were some other
      accidents that were difficult to identify by regular daily practice. CONCLUSION:
      We should be alert to the fact that patients seek a dermatologist after the acute
      phase of injuries. Information on the most common diseases and their
      characteristics can be very useful to practice in ermatologic clinics. The author
      suggests an algorithm to support diagnosis.

PMID- 19851666
TI  - [Acne in women: clinical patterns in different age-groups].
AB  - BACKGROUND: Acne is a frequent skin disease that occurs in both sexes and all age
      groups. Women present several clinical disease patterns; moreover, persistence
      after adolescence is common. OBJECTIVE: To analyze clinical and epidemiological
      characteristics associated with different age-groups affected by acne in women.
      METHODS: Cross-sectional study involving female patients diagnosed with acne, at
      a general dermatology outpatient clinic. Variables related to disease and
      patients were assessed through a standardized questionnaire. RESULTS: One hundred
      and three women were assessed. The average age of patients at the time of the
      consultation was 21.7 +/- 7.3 years. Two groups were defined (cut-off age of 21
      years), with means of 15.8 +/- 2.3 and 28.0 +/- 5.1 years. There was correlation
      between disease duration and current age (R=0.7). There were group differences
      among frequencies of covariables: combined oral contraceptive (OR=48.1), lesions
      located on upper chest (OR=11.6), lesions on upper dorsum (OR=0.2), predominance
      on upper half of face (OR=0.1) and age at disease onset (OR=1.8). Among adult
      women, 80% reported acne onset before 20 years of age. CONCLUSION: Chronologic
      and topographic patterns of female acne in different age-groups were defined,
      reinforcing the importance of an individualized diagnostic and therapeutic
      approach.

PMID- 19851667
TI  - [Val247Leu polymorphism of beta2 glycoprotein 1 gene may justify the genesis of
      anti beta2GP1 antibodies and antiphospholipid syndrome in multibacillary
      leprosy].
AB  - BACKGROUND - Multibacillary (MB) leprosy may be manifested with antiphospholipid
      antibodies (aPL), among which anti-beta2GP1 (beta2-glycoprotein 1). High titers
      of aPL are associated with APS (Antiphospholipid Syndrome), characterized by
      thrombosis. The mutation Val247Leu in the domain V of beta2GP1 exposes hidden
      epitopes with consequent development of anti-beta2GP1 antibodies. OBJECTIVE: To
      evaluate the Val247Leu polymorphism of beta2GP1 gene and its correlation with
      anti-beta2GP1 antibodies in leprosy patients. METHODS: The Val247Leu polymorphism
      was performed by PCR-RFLP and anti-beta2GP1 antibodies were measured by ELISA.
      RESULTS: The genotypic Val/Val was more prevalent in the leprosy group, compared
      to controls. Regarding the 7 MB patients with APS, four presented heterozygosis
      and three, Val/Val homozygosis. Although higher titrations of anti-beta2GP1 IgM
      antibodies were seen in MB leprosy group with Val/Leu and Val/Val genotypes,
      there was no statistical difference when compared to Leu/Leu genotype.
      CONCLUSION: The prevalence of Val/Val homozygosis in leprosy group can partially
      justify the presence of anti-beta2GP1 IgM antibodies in MB leprosy. The
      description of heterozygosis and Val/Val homozygosis in 7 patients with MB
      leprosy and thrombosis corroborates the implication of anomalous phenotype
      expression of beta2GP1 and development of anti-beta2GP1 antibodies, with
      consequent thrombosis and APS.

PMID- 19851668
TI  - [Prevalence of hyperhidrosis in the adult population of Blumenau-SC, Brazil].
AB  - BACKGROUND: Hyperhidrosis is a little known disorder, characterized by excessive
      production of sweat. Hyperhidrosis may occur under several circumstances and
      appears in body parts like armpits, hands, feet, and face, consequently causing
      problems to the patient like job limitation, social embarrassment, and
      psychological damage. OBJECTIVES: Using these theoretical views as a starting
      point, the study aimed to evaluate the prevalence of hyperhidrosis in Blumenau.
      METHODOLOGY: Utilizing interviews, the research was conducted with 500 subjects
      randomly approached, in the period ranging from August 21 to September 1st, 2006.
      RESULTS: 45 respondents (9%) matched the pre-requisites, being classified as
      hyperhidrosis patients. The age group most affected was from 18 to 30 years
      (11.8%). Hyperhidrosis was more frequent among men both in absolute (24 men
      against 21 women) and relative numbers (10.62% of men against 7.66% of women).
      The most prevalent characteristic was 'at least one occurrence per week', in
      91.11% of patients; the least prevalent occurrence was 'cessation of sweat during
      sleep', in 37.77% of respondents. CONCLUSIONS: The data show that the prevalence
      of hyperhidrosis in Blumenau is higher when compared with other studies, thus
      indicating that it is not a rare phenomenon.

PMID- 19851669
TI  - [Fabry disease].
AB  - Fabry disease is an uncommon, X-linked lysosomal storage disorder, caused by
      partial or complete deficiency of the enzyme a-galactosidase A. The defect leads
      to accumulation of uncleaved globotriaosylceramide on the vascular endothelium
      and visceral tissues, being the skin, heart, kidneys and central nervous system
      the most affected organs. We performed review of the literature related to the
      disease and emphasized that early recognition of angiokeratomas and hypohidrosis
      are key diagnostic signs of this serious disease. We also addressed the need of
      multidisciplinary assessment of these patients.

PMID- 19851670
TI  - Sexually transmitted papillomavirus infections: epidemiology pathogenesis,
      clinic, morphology, important differential diagnostic aspects, current diagnostic
      and treatment options.
AB  - The family of human papilloma viruses (HPV) comprises more than 100 genotypes.
      Approximately 30 of the genotypes are responsible for infections in the human
      anogenital area. A precisely defined algorithm with the goal of diagnosing and
      removing HPV for a prolonged or indefinite length of time, as well as to protect
      the patient from any malignant ransformation, does not currently exist. The
      identification of HPV strains by PCR or DNA hybridization in lesional tissue
      provides higher security for the patients. In high-risk patients additional
      colposcopy, rectoscopy, and rethroscopy/cystoscopy increase the probability of
      proper diagnosis and the application of a reliable therapeutic strategy. Removal
      of lesions by means of invasive methods, such as electrodessication, cryosurgery,
      and/or laser therapy, may be successful and could be combined pre- and
      postoperatively with the local application of podophyllotoxin, Trichloroacetic
      acid, 5-fluorouracil epinephrine gel, imiquimod, cidofovir or interferon. The
      administration of vaccine to young patients prevents to a significant extent the
      clinical manifestation of the most frequent viral strains, being HPV-6,-11 and 
      18. The different therapeutic methods must be applied in accordance with the
      clinical picture, taking into account the patient's general status, the presence
      of concomitant diseases, as well as the local and systematic compatibility of the
      side effects of each remedy. The review focuses on the diagnosis and treatment
      options of sexually transmitted HPV-infections and includes synopsis of the most
      recent literature regarding new data of epidemiology, pathogenesis, ifferential
      diagnosis and morphology of HPV infections in humans.

PMID- 19851671
TI  - [Skin biopsy and its histopathologic analysis: Why? What for? How? Part I].
AB  - Histopathologic study is considered gold-standard for diagnosis of skin lesions,
      either neoplastic or inflammatory, most of the times. To take the most out of a
      skin biopsy, physicians should be aware of the reasons for performing the
      procedure followed by microscopic examination, the objectives to be achieved and
      the best manner to do the biopsy, including the best technique and best
      anatomical site for a particular disease.

PMID- 19851672
TI  - [Cutaneous botryomycosis: case report].
AB  - Botryomycosis is a chronic, granulomatous, suppurative bacterial infection
      involving the skin and subcutaneous tissues. The skin lesion is characterized by
      multiple fistulae draining purulent secretion with white-yellowish grains PAS
      positive. The main etiologic agent is Staphylococcus aureus and other less
      frequent pathogens are Pseudomonas aeruginosa and Escherichia coli, isolated or
      associated. The authors report a case of this disease with exuberant lesions on
      the right leg and increased limb volume, fibrous consistency and multiple fistula
      orifices draining white-yellowish grains. Resolution was achieved with
      sulphamethoxazole-trimethoprim.

PMID- 19851673
TI  - [Gnathostomiasis in Brazil: case report].
AB  - Gnathostomiasis is an endemic disease in Asian countries caused by the ingestion
      of larval stage of Gnathostoma sp roundworms that may be acquired by eating raw
      fresh-water fish. It can reach many organs and the skin is one of them,
      characterized by creeping eruptions and/or migrating erythema. Since 1970 the
      number of patients affected seems to be increasing in Central and South America
      countries like Mexico and Peru. This is the first notification and publication of
      gnathostomiasis in Brazil, and it serves as an alert to the possibility of the
      emergence of this disease in non-endemic areas. We report a case of a man who
      traveled to Peru and developed cutaneous features accordant with gnathostomiasis.

PMID- 19851674
TI  - [Langerhans cell histiocytosis: Letterer-Siwe disease - the importance of
      dermatological diagnosis in two cases].
AB  - Langerhans cell histiocytosis is defined as a clonal proliferation of Langerhans
      phenotypic-like cells. Letterer-Siwe disease is the most common and serious of
      these entities, affecting mainly infants up to two years of age. We present two
      cases of this rare disease, diagnosed after dermatological examination,
      highlighting its typical aspects.

PMID- 19851675
TI  - [Inflammation of multiple seborrheic keratoses induced by chemotherapy with
      gemcitabine].
AB  - There are several common mucocutaneous adverse effects related to chemotherapy,
      either by direct cytotoxic action or by hypersensitivity to the drugs. The
      authors report inflammation in multiple seborrheic keratoses after chemotherapy
      with gemcitabine in a patient under treatment for pancreatic cancer. Moreover,
      they discuss the relative benignity of this event and warn about the need to
      correctly identify systemic chemotherapy-induced skin adverse effects.

PMID- 19851676
TI  - [Subcutaneous panniculitis-like T-cell lymphoma].
AB  - Subcutaneous panniculitis-like T-cell lymphoma is extremely rare and has recently
      been recognized as a clinicopathological entity. Young female, 17 years old, has
      complained of subcutaneous nodules and plaques in the limbs and abdomen for three
      years, accompanied of mild weight loss without other constitutional symptoms.
      Nodal, visceral and bone marrow involvement was absent, and subcutaneous CD3/CD8
      atypical lymphocyte infiltration was observed in the skin sample. Chemotherapy
      interrupted the onset of new lesions and led to remission in the 8-month follow
      up. Immunophenotypic and molecular aspects were relevant to the diagnosis and as
      prognosis makers.

PMID- 19851677
TI  - [Splenic tuberculosis during psoriasis treatment with infliximab].
AB  - Psoriasis is a chronic inflammatory disease affecting the skin and occasionally
      the joints. The biological agents have been engineered to target a specific step
      in the inflammatory cascade that leads to psoriasis, including tumor necrosis
      factor, which has a central role in the host defense against Mycobacterium
      tuberculosis. This is a case report about a psoriatic patient who presented
      splenic tuberculosis during treatment with infliximab.

PMID- 19851678
TI  - [Case for diagnosis. Dyschromatosis symetrica hereditaria].
AB  - Dyschromatosis symetrica hereditaria (reticulate acropigmentation of Dohi) is a
      rare autosomal dominant disease. It starts as hyperpigmented and hypopigmented
      macules in reticular pattern on the extremities. We present a case of a 13-year
      old boy that showed hyper and hypopigmented macules distributed on the dorsal
      aspects of the extremities, freckle-like pigmented macules on the face and
      periorbital atrophic linear lesions. Differentiation with others reticulate
      pigmentation manifestations is necessary.

PMID- 19851680
TI  - [Tzanck smears: an old but useful diagnostic tool].
AB  - Tzanck smears can be used for the diagnosis of cutaneous infections, autoimmune
      disorders and cutaneous tumors. To exemplify its use, we report a case of a
      female patient with pemphigus vulgaris whose diagnosis was confirmed by positive
      direct immunofluorescence and conventional cytology using smears obtained by
      scraping the cheek mucosa.

PMID- 19851679
TI  - [Case for diagnosis. Erythema elevatum diutinum].
AB  - Erythema elevatum diutinum is a rare presentation of cutaneous vasculitis.
      Typical lesions are papules, plaques, and nodules that may coalesce and later
      turn to yellow-brown color. The extensor surface of the extremities is the most
      involved area and older lesions may present xanthomatous appearance. Light
      microscopy of acute lesions shows neutrophilic, perivascular infiltrate with
      dermal fibrin deposits, endothelial expansion, and leukocytoclasis. We present a
      case of erythema elevatum diutinum without associated disease.

PMID- 19851684
TI  - [Not Available].

PMID- 19851685
TI  - Hematological and hemostaseological alterations after warm and cold limb ischemia
      reperfusion in a canine model.
AB  - PURPOSE: Acute ischemia-reperfusion (I/R) of extremities means serious challenge
      in the clinical practice. Furthermore, the issue of preventive cooling is still
      controversial. In this canine model we investigated whether limb I/R -with or
      without cooling- has an influence on hematological and hemostaseological factors.
      METHODS: Femoral vessels were exposed and clamped for 3 hours. After release the
      clamps, 4-hour reperfusion was secured. The same procedures with cooling using
      ice bags, as well as warm and cold sham-operations were performed. Before
      operations, from the excluded limb by the end of ischemia, during the
      reperfusion, and for 5 postoperative days afterwards blood samples were collected
      for testing hematological and blood coagulation parameters. RESULTS: After I/R
      activated partial thromboplastin time was elongated on 2nd-4th postoperative
      days. The highest values were on the 2nd day in cold I/R group, accompanied by
      increased prothrombin time values. The hematological parameters and fibrinogen
      level showed non-specific changes. In excluded ischemic limb the blood
      composition showed controversial data. Cold ischemia induced larger alterations,
      however platelet count, hematocrit changed more expressly in warm ischemia.
      CONCLUSION: These results indicate the risk of coagulopathy following limb I/R on
      early post-eventually days, which risk is higher in the case of cold I/R.

PMID- 19851686
TI  - An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease:
      experimental study in young rats.
AB  - PURPOSE: To test the hepatoprotective effect of water extract from Bidens Pilosa
      L. (BPE) in cholestatic liver disease induced by ligature and resection of the
      common bile ducts (LRBD) in young rats. METHODS: We studied four groups of ten 21
      days old (P21) Wistar rats, Group SW: sham operation and water; Group SD: sham
      operation and BPE (160 mg of fresh leaves/100 g of body weight/day); Group LW:
      LRBD and water and Group LD: LRBD and BPE daily. Pentobarbital sleeping time
      (PST) and serum activities of aspartate aminotransferase (AST) and of alanine
      aminotransferase (ALT) were determined after the sacrifice (P70). A Ruwart's
      score for hepatic fibrosis (RS) was given to each animal. Were employed two way
      ANOVA and the test of Tukey or a non-parametric test for multiple comparisons.
      RESULTS: There were statistically significant differences between LW and LD in
      the measurements of the PST ((means LW=390; LD=173), AST (means LW=8, LD=5), ALT
      (medians LW=2; LD=1) e RS (medians LW=2; LD=1). CONCLUSION: BPE could be used in
      the phytotherapy of the hepatic damage induced by chronic obstructive
      cholestasis, because protects liver function, decreases the rate of necrosis and
      liver fibrosis in cholestatic liver disease.

PMID- 19851687
TI  - Esophagectomy and substitution of the thoracic esophagus in dogs.
AB  - PURPOSE: To evaluate a technique to remove the thoracic esophagus without
      thoracotomy and two methods for thoracic esophageal replacement in dogs. METHODS:
      27 ex-vivo dogs were divided into three groups in order to evaluate: G1 - total
      thoracic esophagectomy by the everting stripping method; G2 - total thoracic
      esophagectomy and esophageal substitution using the whole stomach; G3 - total
      thoracic esophagectomy and esophageal substitution using fundus rotation
      gastroplasty. After esophageal resection in G1, the integrity of the
      intrathoracic route was evaluated by endoscopy and tested with 1% methylene blue
      solution. RESULTS: Visceral pleural rupture was observed in all animals. However,
      this intrathoracic route made it possible to bring both esophagus substitutes (G2
      and G3) to be anastomosed to the cut end of the cervical esophagus. CONCLUSIONS:
      Thoracic esophageal substitution using the whole stomach showed less anastomotic
      tension and was less technically demanding than the fundus rotation gastroplasty
      method. The ex-vivo results support further studies to validate the techniques in
      clinical cases.

PMID- 19851688
TI  - Comparison between electrosurgery and cold blade in tongues of rats: a
      preliminary experimental study.
AB  - PURPOSE: To compare tissue cicatrization in the tongue of rats using
      electrosurgery and the cold blade. METHODS: Ten adult male Wistar rats were
      divided into two groups of 5 animals each, according to the time of sacrifice (3
      and 7 days). Each animal had two incisions, one made with a cold blade and the
      other with an electric blade, both of which were approximately 0.5 mm in length.
      Following sacrifice of the animals, the tongues were submitted to a histological
      study in order to classify the presence of angiogenesis, fibroblastic
      proliferation, epithelial proliferation and inflammatory cells as good, moderate
      and weak. RESULTS: The wound made with electric blade presented a delay in the
      healing process and a greater inflammatory response as compared with the cold
      blade, despite the fact that there was no statistically significant difference
      (p<0.05). CONCLUSION: There were no significant statistical differences between
      electrosurgery and the cold blade in relation to angiogenesis, fibroblastic
      proliferation, epithelial proliferation or the presence of inflammatory cells at
      any time of evaluation.

PMID- 19851689
TI  - Healing reaction to mammary prostheses covered by textured silicone and silicone
      foam in rats.
AB  - PURPOSE: To compare the capsular reaction to two different coverings of silicone
      prosthesis through the biophysical characteristic of adherence and microscopical
      aspects of the inflammatory reaction and collagen formation. METHODS: Thirty two
      Wistar rats were used. In the dorsum of each animal a silicone elastomer with a
      smooth superficies and another coated with texturized silicone (Mentor) was
      implanted. Another one, with the same smooth superficies and other coated with
      silicone foam (Lifesil), making up in each side, of the dorsum, the texturized
      and silicone foam group respectively. The animals were split into four groups to
      be evaluated at 7, 14, 30 and 60 days. On the evaluation dates the implant
      adherence was verified witch a tensiometer and the values in kgf were obtained.
      The material was sent to histological analysis with hematoxilin-eosin and
      picrosirius colorations, to evaluate the inflammatory reaction and collagen
      synthesis, respectively. The obtained data were submitted to statistical
      treatment. RESULTS: There was more adherence of the tissue to the silicone foam
      (P<0,001). The inflammatory reaction was more intense in the same group, but
      without statistical significance. The number of giant cells and granulomas were
      more frequent in the silicone foam group. There was statistical significance at
      the 60 days for granulomas (P<0,028) and for all subgroups about number of giant
      cells (P< 0,012 to P<0,036). The thickness of the capsule in the silicone foam
      group was bigger, with statistical significance at seven days (P<0,028) and 60
      days (P<0,012). The collagen deposition showed no difference in statistical
      analysis. CONCLUSION: The capsular reaction to the silicone foam showed stronger
      adherence, bigger thickness and had more number of granulomas and giant cells. No
      difference was observed in the intensity of inflammatory reaction in relation to
      type I and III collagen, when compared to the texturized cover.

PMID- 19851690
TI  - Farnesol inhibits cell proliferation and induces apoptosis after partial
      hepatectomy in rats.
AB  - PURPOSE: To study farnesol (FOH) effects on liver regeneration after 70% partial
      hepatectomy (PH) in rats. METHODS: Animals received FOH (25 mg/100 g body
      weight/day) or corn oil (CO, 0.25 mL/100 g body weight/day, controls). After a 2
      week-treatment, all animals were subjected to PH and euthanized at different time
      points (0 h, 0.5 h, 4 h, 8 h, 18 h and 24 h) after surgery. Hepatic cell
      proliferation (PCNA positive nuclei) and apoptosis (fluorescence microscopy) were
      evaluated. RESULTS: Compared to CO treatment, FOH treatment inhibited (p<0.05)
      cell proliferation at 24h (S phase of the cell cycle) after PH. This was preceded
      by an induction of apoptosis 0.5 h (p<0.05; G(0)/G(1) transition phase) after
      surgery. CONCLUSION: The results of the present study suggest that apoptosis
      induction could be associated with the reduced number of cells at the S phase
      observed in FOH group. These novel in vivo data reinforce FOH as a promising
      chemopreventive and therapeutic agent against cancer.

PMID- 19851691
TI  - Effect of an extract of Aloe vera on the biodistribution of sodium pertechnetate
      (Na99mTcO4) in rats.
AB  - PURPOSE: Aloe vera is a tropical plant popularly known in Brazil as babosa. We
      have investigated the effect of aqueous extract of Aloe vera on the
      biodistribution of Na99mTcO4 and laboratorial parameters in Wistar rats. METHODS:
      Twelve animals were divided into treated and control groups. In the treated
      group, Aloe vera was given by gavage (5mg/mL/day) during 10 days. The control
      group received sorbitol by the same way and period. One hour after the last dose,
      we injected 0.1mL of Na99mTcO4 by orbital plexus. After 60 min, all the animals
      were killed. Samples were harvested from the brain, liver, heart, muscle,
      pancreas, stomach, femur, kidneys, blood, testis and thyroid and the percentage
      of radioactivity (%ATI/g) was determined. Biochemical dosages were performed.
      RESULTS: There was a significant increase of %ATI/g in blood, femur, kidneys,
      liver, stomach, testis and thyroid and also in blood levels of AST and ALT. A
      significant decrease in levels of glucose, cholesterol, triglycerides, creatinine
      and urea occurred. The statistical analyses were performed by Mann-Whitney test
      and T-Student test (p<0.05). CONCLUSION: The aqueous extract of Aloe vera
      facilitated the uptake of Na99mTcO4 in organs of rats and it was responsible to a
      high increase of levels of AST and ALT.

PMID- 19851692
TI  - Study on the vaginal smear of rats submitted to autologous ovarian transplant:
      impact of remote ischemic preconditioning.
AB  - PURPOSE: To evaluate the remote ischemic preconditioning (R-IPC) impact on the
      quality of the ovarian graft by means of vaginal smear of transplanted rats.
      METHODS: Sixty rats were used divided in six groups: Control; Fresh transplant
      (TxF); Cryopreserved transplant (TxC); R-IPC; R-IPC + fresh transplant (TxF+R
      IPC); R-IPC + cryopreserved transplant (TxC+R-IPC). R-IPC was performed in the
      common iliac artery. Autologous ovarian tissue was implanted integrally in the
      retro peritoneum. On the first PO day, vaginal smear collection was daily
      initiated. After 30 days, the PO day when the estrous cycle was re-initiated was
      considered for analysis as well as the estrous days and the number of estrous
      cycles. RESULTS: R-IPC showed a tendency to an early estrus re-initiation
      (p>0.05) as well as increase the number of cycles in the fresh transplanted group
      while in the cryopreserved transplant the number of cycles was similar,
      regardless of the stimulus R-IPC (p>0.05). The animals which had undergone fresh
      grafts had a longer estrous period than the ones which had undergone
      cryopreserved grafts, with or without R-IPC (p<0.05). CONCLUSION: R-IPC promoted
      earlier re-initiation of ovarian activity in the PO and greater estrous
      frequency, with more consistent results in the fresh grafts than in the
      cryopreserved ones.

PMID- 19851693
TI  - Early morphological and histochemical alterations in rats subjected to
      ileocystoplasty.
AB  - PURPOSE: To study morphologic and histochemical alterations arising at the
      ileocystoplasty site. METHODS: Sixteen Wistar female rats were subjected to
      ileocystoplasty and sacrificed after eight weeks. Material collected was divided
      into four groups for histological and histochemical studies: Group I (control) -
      isolated ileum segment removed during ileocystoplasty; Group II - ileoileal
      anastomosis; Group III - ileovesical anastomosis and Group IV - ileal segment
      from the neobladder. Histological and histochemical study assessed dysplasia,
      metaplasia, acute and chronic inflammation, fibrosis, atrophy, hypertrophy, total
      mucins, sialomucins and sulfomucins. The non-parametric Wilcoxon and Mann-Whitney
      tests were employed in statistical analysis. RESULTS: None of the groups
      presented dysplasia. Acute inflammation and atrophy occurred in Groups II, III
      and IV, not reaching statistical significance. Metaplasia was significant only in
      Group III (p=0.012). Chronic inflammation, fibrosis and hypertrophy were
      significant in Groups II, III and IV. There was a significant increase in total
      mucin content in Group IV (p=0.014) and a reduction in Group III (p=0.016).
      Increases in sialomucins were observed in samples for Groups III (p=0.003) and IV
      (p=0.002) along with reduced sulfomucins in samples from Groups III (p=0.013) and
      IV (p=0.008). CONCLUSION: Ileocystoplasty in female rats caused squamous
      metaplasia, chronic inflammatory infiltration, fibrosis, hypertrophy, increase in
      sialomucin content, reduction in sulfomucins, and alterations in total mucin
      content with statistical significance, as well acute inflammatory infiltration
      and muscular atrophy with less intensity.

PMID- 19851694
TI  - Comparative study of technique to obtain stem cells from bone marrow collection
      between the iliac crest and the femoral epiphysis in rabbits.
AB  - PURPOSE: To assess the technique for the collection of rabbit bone marrow stem
      cells from different regions to be used as an experimental model in regenerative
      medicine. METHODS: Thirty rabbits were allocated into 2 groups: GROUP A, n=8,
      animals that underwent bone marrow blood (BMB) harvesting from the iliac crest;
      and GROUP B: including 22 rabbits that underwent BMB harvesting from the femur
      epiphysis. After harvesting, mononuclear cells were isolated by density gradient
      centrifugation (Ficoll - Histopaque). The number of mononuclear cells per ml was
      counted in a Neubauer chamber and cell viability was checked through Tripan Blue
      method. RESULTS: Harvesting from the iliac crest yielded an average of 1 ml of
      BMB and 3,6.10(6) cells/ml over 1 hour of surgery, whereas an average of 3ml of
      BMB and 11,79.10(6) cells./ml were obtained in 30 min from the femur epiphysis
      with a reduced animal death rate. CONCLUSION: The analysis for the obtention of a
      larger number of mononuclear cells/ml from rabbit bone marrow blood was more
      satisfactory in the femur epiphysis than in the iliac crest.

PMID- 19851695
TI  - Relationship between peripheral and mesenteric serum levels of CEA and CA 242
      with staging and histopathological variables in colorectal adenocarcinoma.
AB  - PURPOSE: To compare histopathological variables and staging in colorectal
      adenocarcinoma cases with CEA and CA 242 in peripheral and mesenteric blood.
      METHODS: In 169 individuals underwent surgery for colorectal cancer, CEA and CA
      242 were analyzed and compared to mesenteric and peripheral blood and correlated
      with macroscopic tumor's morphology and size, degree of cell differentiation,
      venous, neural and lymphatic involvement and TNM classification. RESULTS: There
      was a difference between the mesenteric (M) and peripheral (P) serum levels of
      CEA (p=0.020). Higher levels of markers were correlated with venous invasion CEA
      (P) p=0.013, CEA (M) p=0.05, CA 242 (M) p=0.005 and CA 242 (P) p=0.038; with
      advanced staging CEA (P) < CEA (M) (p < 0.05); CA 242 (P) < CA 242 (M) (p <
      0.05); and with greater dimensions CEA (P) < CEA (M) (p < 0.001); CA 242 (P) < CA
      242 (M) (p < 0.001). CA 242 became higher with neural invasion (P): p=0.014, (M):
      p=0.003). CONCLUSIONS: There were higher mesenteric than peripheral levels of
      CEA. Both mesenteric and peripheral levels of CEA and CA 242 were higher in
      neoplasm with venous involvement, greater diameter and advanced stages. There was
      a correlation between CA 242 and neural invasion.

PMID- 19851696
TI  - Should complete stripping operation to the ankle be avoided in the treatment of
      primary varicose veins due to greater saphenous vein insufficiency?
AB  - PURPOSE: The most preferred method for the treatment of primary varicose veins
      due to greater saphenous vein (GSV) insufficiency is saphenofemoral high ligation
      and thigh stripping of the GSV, and ambulatory phlebectomy. Stripping is usually
      ended at the knee level to prevent nerve injury in the calf. However, different
      surgical modalities may be used depending on the surgeon's choice and experience.
      METHODS: We present the results of complete stripping of the GSV to the ankle and
      ambulatory phlebectomies performed by a single surgeon. Ninety-six patients (102
      limbs) who underwent standardized surgical procedure were participated in this
      study. Median follow-up time was 3.4 years. RESULTS: All complaints due to
      varicose veins were resolved in all extremities. Some temporary complications
      observed were resolved fully during follow-up. Permanent paresthesia which was
      the most important complication was found only in two patients (2%). No
      recurrence was observed. CONCLUSION: The risk of saphenous nerve injury in the
      calf should not to be considered a reason to avoid complete stripping of the GSV
      to the ankle. If it is applied carefully and with appropriate technique, complete
      stripping still seems to be a good treatment option.

PMID- 19851697
TI  - Clinical, manometric and profilometric evaluation after surgery for
      Hirschsprung's disease: comparison between the modified Duhamel and the transanal
      rectosigmoidectomy techniques.
AB  - PURPOSE: To evaluate fecal continence, anorectal manometry (AM) and profilometry
      (P), in patients operated for congenital megacolon, using either the modified
      Duhamel technique (MDT) or the modified transanal rectosigmoidectomy (MTR)
      technique. METHODS: 42 patients were evaluated clinically and via AM and P, for
      postoperative control. The resting, coughing, voluntary contraction, maintained
      voluntary contraction and perianal stimulation pressures were investigated. The
      rectosphincteric reflex was tested and the simple and enhanced pressure curves
      were evaluated. The three-dimensional profilometric outline was produced.
      Student's t, chi-squared and Fisher's exact tests were used for statistical
      analysis (p<0.05). RESULTS: AM showed mean resting pressures of 53.44 mmHg for
      MDT and 60.67 mmHg for MTR, and mean voluntary contraction pressures of 94.50
      mmHg for MDT and 95.47 mmHg for MTR. There was no statistical difference between
      the groups. The shapes of the simple and enhanced pressure curves did not present
      any statistical difference, independent of the surgical technique used.
      CONCLUSION: The two surgical techniques were equivalent. MDT caused greater
      incidence of postoperative constipation that MTR did. AM and P were shown to be
      excellent tests for postoperative follow-up among these patients.

PMID- 19851698
TI  - Is animal experimentation fundamental?
AB  - The understanding about the utilization of experimental animals in scientific
      research and in teaching is many times a complex issue. Special attention needs
      to be paid to attain the understanding by the general public of the importance of
      animal experimentation in experimental research and in undergraduate medical
      teaching. Experimental teaching and research based on the availability of animals
      for experimentation is important and necessary for the personal and scientific
      development of the physician-to-be. The technological arsenal which intends to
      mimic experimentation animals and thus fully replace their use many times does
      not prove to be compatible with the reality of the living animal. The purpose of
      this paper is to discuss aspects concerning this topic, bringing up an issue
      which is complex and likely to arouse in-depth reflections.

PMID- 19851699
TI  - Fate of abstracts presented at an International Commission on Occupational Health
      (ICOH) congress--followed by publication in peer-reviewed journals?
AB  - OBJECTIVES: Presentations at international meetings offer an excellent way to
      disseminate current research findings. One measure of the quality of research is
      its subsequent publication. Our study aimed to determine the publication rate of
      abstracts presented at a congress of the International Commission of Occupational
      Health (ICOH), and to identify predictive factors of publication and differences
      between presented abstracts and -subsequently published papers. METHODS: We
      identified a random sample of 318 abstracts presented at the 2000 ICOH meeting
      from the book of abstracts. Using Medline and Embase, we assessed their
      publication rate in the period ranging from 1998 to 2006 and investigated the
      factors associated with publication rate. RESULTS: Of 318 abstracts originating
      from 51 countries, 105 articles [33%, 95% confidence interval (95% CI) 27-38)]
      were subsequently published in 67 journals indexed in Medline or Embase. Mean
      time to publication was 17 months (95% CI 13-21). Multivariate analysis revealed
      that abstracts with quantitative data and written by authors originating from
      developed countries were significantly more published. From the time of abstract
      presentation to publication in a peer-reviewed journal, both the study sample
      size and the first author frequently changed (respectively 25% and 29%), but the
      overall conclusions remained stable, except in one case. CONCLUSIONS: Most of the
      abstracts presented at the 2000 ICOH congress were not subsequently published as
      full research reports. If this is the case for most abstracts submitted to
      conferences, this may limit the ability of a reader to judge the validity,
      reliability, and generalizability of the research presented. Caution is advised
      when referencing or generalizing from abstracts that have not been subsequently
      published in full.

PMID- 19851700
TI  - The interplay between physical activity at work and during leisure time--risk of
      ischemic heart disease and all-cause mortality in middle-aged Caucasian men.
AB  - OBJECTIVE: Our aim was to test the hypothesis that a high level of physical
      activity during leisure time increases the risk of ischemic heart disease (IHD)
      mortality among men with high physical work demands. METHODS: We carried out a 30
      year follow-up of the Copenhagen Male Study of 5249 caucasian, male workers aged
      40-59 years; 274 men with overt cardiovascular disease were excluded from the
      follow-up. RESULTS: During the follow-up period, 591 men (11.9%) died from IHD.
      Cox analyses of men with low (N=1236), medium (N=2651), and high (N=858) physical
      work demands showed that those with high demands had a higher risk of IHD
      mortality compared to men with low demands [age-adjusted hazard ratio 1.51, 95%
      confidence interval (95% CI) 1.18-1.94]. In all three groups, men with a low
      level of physical activity during leisure time had a higher risk of IHD than men
      with a medium or high level. Overall, the age-adjusted hazard ratio for IHD
      mortality associated with a high level of leisure time physical activity was 0.49
      (95% CI 0.34-0.70). Among workers with high physical work demands, the hazard
      ratio for IHD mortality (adjusted for confounders) was 0.82 (95% CI 0.42-1.56)
      for a high level of leisure time physical activity and 0.62 (95% CI 0.40-0.97)
      for a moderate level. CONCLUSION: We did not find support for the hypothesis that
      a high level of physical activity during leisure time increases the risk of IHD
      mortality among men with high physical work demands and with no pre-existing
      clinical cardiovascular disease. In contrast, moderate and high levels of
      activity during leisure time seemed to be protective against IHD mortality among
      people with medium and high physical activity at work.

PMID- 19851702
TI  - Measuring fit of sequence data to phylogenetic model: gain of power using
      marginal tests.
AB  - Testing fit of data to model is fundamentally important to any science, but
      publications in the field of phylogenetics rarely do this. Such analyses discard
      fundamental aspects of science as prescribed by Karl Popper. Indeed, not without
      cause, Popper (Unended quest: an intellectual autobiography. Fontana, London,
      1976) once argued that evolutionary biology was unscientific as its hypotheses
      were untestable. Here we trace developments in assessing fit from Penny et al.
      (Nature 297:197-200, 1982) to the present. We compare the general log-likelihood
      ratio (the G or G (2) statistic) statistic between the evolutionary tree model
      and the multinomial model with that of marginalized tests applied to an alignment
      (using placental mammal coding sequence data). It is seen that the most general
      test does not reject the fit of data to model (P approximately 0.5), but the
      marginalized tests do. Tests on pairwise frequency (F) matrices, strongly (P <
      0.001) reject the most general phylogenetic (GTR) models commonly in use. It is
      also clear (P < 0.01) that the sequences are not stationary in their nucleotide
      composition. Deviations from stationarity and homogeneity seem to be unevenly
      distributed amongst taxa; not necessarily those expected from examining other
      regions of the genome. By marginalizing the 4( t ) patterns of the i.i.d. model
      to observed and expected parsimony counts, that is, from constant sites, to
      singletons, to parsimony informative characters of a minimum possible length,
      then the likelihood ratio test regains power, and it too rejects the evolutionary
      model with P << 0.001. Given such behavior over relatively recent evolutionary
      time, readers in general should maintain a healthy skepticism of results, as the
      scale of the systematic errors in published trees may really be far larger than
      the analytical methods (e.g., bootstrap) report.

PMID- 19851701
TI  - Profiles of disability among adults with bipolar spectrum disorders.
AB  - BACKGROUND: Heterogeneous groups of patients with a spectrum of service needs are
      commonplace in mental health settings. Although comprehensive assessments are
      available to measure variations in service needs, numerous challenges still exist
      when confronting this heterogeneity and many assessments used in clinic settings
      are lengthy and have not been demonstrated to be consistent over time. OBJECTIVE:
      The purpose of this study was to identify subgroups of persons with bipolar
      spectrum disorders, who have similar disability profiles, and to the extent to
      which the subgrouping is stable over time. METHODS: Participants were recruited
      from the Continuous Improvement for Veterans in Care-Mood Disorders. Eligible
      patients (N = 435) were those who received inpatient or outpatient treatment for
      bipolar disorder at a large urban VA mental health facility in Western
      Pennsylvania from July 2004 through July 2006. This was a naturalistic cohort
      study of patients with bipolar spectrum disorders. Baseline and 1-year follow-up
      data were collected using face-to-face interviews and recorded abstraction. The
      World Health Organization Disability Assessment Scale was the primary measure
      used to identify subgroups within this sample. RESULTS: Using a classification
      strategy called latent profile analysis, this study identified three unique
      subgroups that showed significant differences in various clinical measures at
      baseline and follow-up. The largest and most consistent subgroup differences were
      observed in the current bipolar symptomatology. CONCLUSION: The classification of
      functional status in the present study can aid clinicians in the identification
      of bipolar patients, with specific impairment profiles, who may need additional
      intervention. Future research is needed to understand whether specific
      interventions targeted at these subgroups can improve the quality of care for
      this high-need and at-risk population.

PMID- 19851703
TI  - Influences of sex, habitat, and seasonality on heavy-metal concentrations in the
      burrowing crab (Neohelice granulata) from a coastal lagoon in Argentina.
AB  - Cadmium, chromium, copper, and manganese concentrations were determined in
      hepatopancreas of both sexes as well as in eggs at different embryonic
      development stages of the burrowing crab Neohelice granulata (Brachyura,
      Varunidae) from Mar Chiquita Coastal Lagoon, a biosphere reserve from Argentina,
      during a period of 1 year, to assess the bioaccumulation of metals associated
      with sex and seasonality. Furthermore, metal levels in associated superficial
      sediment samples were also determined. Two different "cangrejales," one in a
      mudflat and another one in a salt marsh, were studied. The results showed high
      concentrations of copper within the hepatopancreas, which was considered a strong
      reflection of high exposure of N. granulata to this metal. Metal accumulation in
      hepatopancreas from both study sites and sexes did not present significant
      differences, as did seasonality. In this sense, both spring and summer metal
      levels in hepatopancreas were the greatest. Eggs did not present differences in
      metal accumulation, with the exception of manganese, between sites or between
      crabs at different embryonic stages. For this metal, eggs from female crabs
      inhabiting mudflats showed higher levels than those from inhabiting salt marshes.
      Moreover, eggs in the late embryonic stage also showed the highest manganese
      concentrations. Metal levels in sediments, however, were similar in both sites.
      These are the first results of metal level in biota and sediments in this
      particular environment. Such results could be used as a baseline for the
      monitoring of metal levels in future studies in Mar Chiquita Coastal Lagoon.

PMID- 19851704
TI  - Surgical treatment of hilar cholangiocarcinoma in the new era: the Asan
      experience.
AB  - BACKGROUND/PURPOSE: Both curative resection and minimized in-hospital mortality
      offer the only chance of long-term survival in patients with hilar
      cholangiocarcinoma. The reported resectability rates for hilar cholangiocarcinoma
      have increased by virtue of combined major hepatectomy, but this procedure is
      technically demanding and still associated with a significant morbidity and
      mortality that must be carefully balanced against the chances of long-term
      survival. METHODS: Between January 2001 and December 2008, 350 patients with
      hilar cholangiocarcinoma underwent exploration for the purpose of potentially
      curative resection, of whom 302 (86.3%) were resected in the Department of Hepato
      Biliary Surgery and Liver Transplantation, Asan Medical Center, University of
      Ulsan College of Medicine. Combined hepatectomy was carried out in 268 (88.7%) of
      302 resected patients. Major hemihepatectomy and parenchyma-preserving
      hepatectomy were performed in 257 and 11 patients, respectively. Portal vein
      resection was associated in 40 (14.9%) of 268 hepatectomized patients. To control
      preoperative cholangitis and reduce risk of postoperative hepatic failure,
      biliary decompression through endoscopic and/or percutaneous transhepatic
      drainage and portal vein embolization were preoperatively applied in 329 (94.0%)
      of 350 explored patients and in 91 (54.2%) of 168 extended hepatectomized
      patients (154 right hemihepatectomy, 9 right trisectionectomy, 5 left
      trisectionectomy), respectively. Liver transplantation was not performed as
      primary treatment for hilar cholangiocarcinoma. RESULTS: There were 5 cases
      (1.7%) of in-hospital death after resection and 1 postoperative liver failure
      that was successfully treated with liver transplantation. Major complications
      were encountered in 23 patients (7.0%), and the overall morbidity rate was 43%.
      In 302 resections, 214 (70.9%) were curative resections (R0) and 88 (29.1%) were
      palliative resections (R1). The overall 1-, 3- and 5-year survival rates after
      resection, including in-hospital deaths, were 84.6, 50.7 and 47.3% in the R0
      group and 69.9, 33.3 and 7.5% in the R1 group, respectively. The 5-year survival
      rate of extended hemihepatectomy of 36.4% was better than that of parenchyma
      preserving hepatectomy at 10.5%. Two significant predictive factors adversely
      affecting survival after resection were lymph node metastasis and incurability of
      surgery (P < 0.001). Two patients with vascular involvement who underwent
      concomitant hepatic artery and portal vein reconstruction are alive after more
      than 3 years. CONCLUSION: Preoperative biliary decompression and portal vein
      embolization enabled us to reduce in-hospital deaths associated with extended
      hepatectomy for hilar cholangiocarcinoma. Major hemihepatectomy offers an
      increased survival because of the higher possibility of curative resection than
      bile duct resection alone and parenchyma-preserving hepatectomy, but it still
      carries a certain mortality. Less extensive procedures can be conducted safely
      and are beneficial for aged patients in poor condition with a less advanced tumor
      stage if tumor-free resectional margins are obtained.

PMID- 19851705
TI  - Effectiveness and tolerability of citalopram for the treatment of depression and
      anxiety disorders in children and adolescents: an open-label study.
AB  - To assess the effectiveness and tolerability of citalopram for the acute
      treatment of children and adolescents suffering from depression and/or anxiety
      disorders. As much as 78 outpatients, aged 7-18 years with a diagnosis of
      depressive and/or anxiety disorder, completed an 8-week open trial with
      citalopram (20-40 mg/day). Outcome, side effects and suicidality were assessed
      weekly to bi-weekly using appropriate rating scales. At endpoint 56% of subjects
      were found to be responders (Clinical Global Impression-Improvement [CGI-I] Scale
      <or= 2). Subjects with less severe psychopathology and subjects with anxiety
      disorders showed a more favorable response. As much as 43% of depressed and 51%
      of anxious subjects had a 50% or greater reduction in scores on our secondary
      outcome measures, Children's Depression Rating Scale-Revised (CDRS-R) and Screen
      for Child Anxiety Related Emotional Disorders (SCARED). Most reported adverse
      events were mild to moderate and did not affect medication adherence. No increase
      in suicidality was observed during the study. Citalopram was moderately
      effective, generally well tolerated and safe for the acute treatment of depressed
      and anxious children and adolescents.

PMID- 19851706
TI  - Recurrent postoperative perineal hernia: laparoscopic redo mesh repair.
AB  - Symptomatic perineal herniation after abdominoperineal resection is a rare
      complication and its management remains challenging. Recurrent symptomatic
      perineal hernia after a previous laparoscopic mesh repair is exceptional and no
      standardized procedure has been deemed the "gold standard of care." To date, this
      redo laparoscopic mesh repair is only the second report that we could find in the
      English literature.

PMID- 19851707
TI  - A sonographic spectrum of psoriatic arthritis: "the five targets".
AB  - Ultrasound is a rapidly evolving technique that is gaining an increasing success
      in the assessment of psoriatic arthritis. Most of the studies have been aimed at
      investigating its ability in the assessment of joints, tendons, and entheses in
      psoriatic arthritis patients. Less attention has been paid to demonstrate the
      potential of ultrasound in the evaluation of skin and nail. The aim of this
      pictorial essay was to show the main high-frequency grayscale and power Doppler
      ultrasound findings in patients with psoriatic arthritis at joint, tendon,
      enthesis, skin, and nail level.

PMID- 19851708
TI  - A review of tuberculosis-related referrals among children in Ireland.
AB  - BACKGROUND: Immigration has been shown to have an increasingly important effect
      on the epidemiology of tuberculosis (TB) in developed countries. AIM: To review
      patterns of TB-related referrals to a paediatric infectious diseases clinic.
      METHODS: Retrospective chart review of TB-related referrals of children attending
      the Rainbow Clinic at OLCHC between 2003-2005. RESULTS: Forty-seven children were
      assessed: 18 referred from public health clinics, 5 from general practitioners,
      and 24 from paediatricians. Most common reason for referral was history of TB
      exposure (60%). Eighteen (38%) were female, 29 (62%) were male. Thirteen (28%)
      had latent TB, and 17 (36%) had active disease. Of children with TB disease, 25
      (83%) were Caucasian Irish, and the remainder was African. Twenty-five children
      completed TB treatment and were discharged, and 2 (7%) were lost to follow-up.
      CONCLUSION: Our study highlights the problem of TB in children, the majority of
      whom are native to this country.

PMID- 19851709
TI  - Prevalence and demographic factors of smoking in Morocco.
AB  - OBJECTIVES: To study the prevalence and determinants of cigarette smoking in
      Morocco. METHODS: A sample of 9,195 individuals aged 15-90 years, were randomly
      selected, using a stratified cluster sampling technique. A cross-sectional,
      household, community-based survey was conducted using a tested questionnaire. The
      interview covered personal, social and educational characteristics of the
      respondents and their smoking status. The association between current smoking and
      sociodemographic variables was estimated. RESULTS: The overall prevalence of
      current smoking was 31.5% for males and 3.1% for females. In men, smoking was
      associated with lower educational level. In women, it was associated with higher
      educational level and social class. CONCLUSION: Cigarette smoking remains an
      important public health problem in Morocco. A comprehensive strategy for tobacco
      control is needed.

PMID- 19851710
TI  - Eugenol inhibits cell proliferation via NF-kappaB suppression in a rat model of
      gastric carcinogenesis induced by MNNG.
AB  - The modulation of intracellular nuclear factor-kappaB (NF-kappaB) signaling
      pathway involved in the deregulated expression of cell proliferation and cell
      cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol
      (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of
      cloves is known to possess attractive remedial features. In the present study, we
      investigated the modulatory effects of eugenol on NF-kappaB signaling in a rat
      model of gastric carcinogenesis induced by N-methyl-N(')-nitro-N-nitrosoguanidine
      (MNNG) by analysing the expression of nuclear factor-kappaB (NF-kappaB) family
      members ((NF-kappaB (p50 and p65), inhibitor of kappaB alpha (IkappaBalpha),
      phosphorylated IkappaBalpha (p-IkappaBalpha), IkappaB kinase beta (IKKbeta)) and
      the NF-kappaB target genes that promote (e.g., cyclin D1, cyclin B and PCNA) or
      inhibit (e.g., p53, p21, and Gadd45) cell proliferation and cell survival. MNNG
      induced gastric tumours were characterized by NF-kappaB activation that
      correlated with upregulation of IKKbeta, and phosphorylation and degradation of
      IkappaBalpha. Furthermore, upregulation of cyclins and PCNA with downregulation
      of p21, p53, and Gadd45 suggested that the proliferative advantage in gastric
      carcinomas is dependent on elevated constitutive NF-kappaB activity.
      Administration of eugenol significantly reduced the incidence of MNNG-induced
      gastric tumours by suppressing NF-kappaB activation and modulating the expression
      of NF-kappaB target genes that regulate cell proliferation and cell survival. The
      targeting of NF-kappaB signaling pathway by eugenol may have a significant impact
      on chemopreventive and therapeutic approaches for cancer.

PMID- 19851711
TI  - Tolfenamic acid decreases c-Met expression through Sp proteins degradation and
      inhibits lung cancer cells growth and tumor formation in orthotopic mice.
AB  - The nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA) is emerging
      as a new anti-cancer agent. TA induces the degradation of specific Specificity
      protein (Sp) transcription factors, Sp1, Sp3 and Sp4 which are associated with
      tumor growth and metastasis. In this study we have evaluated the effect of TA on
      lung cancer using both in vitro and in vivo models. TA in a dose dependent manner
      inhibited proliferation and cell viability of two different lung cancer cells,
      A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of
      Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed
      in a variety of cancers including lung cancer and Sp proteins mediate the
      regulation of c-Met. TA diminished the expression of c-Met protein and modulates
      its downstream signaling pathway. Furthermore, TA treatment significantly
      increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax
      confirming the activation of apoptotic pathways. In vivo studies using the
      orthotopic mice model for lung cancer showed that TA (25 mg/kg/2 days and 50
      mg/kg/2 days) resulted in a dose dependent decrease in tumor formation. The
      immunohistochemical staining of lung tissue showed high expression of Sp1, Sp3,
      Sp4, c-Met and phospho Met in control group and a dose dependent decrease in TA
      treated groups. The crucial findings of this study support that targeting c-Met
      with a potent inhibitor of Sp proteins is a robust strategy for the implications
      in lung cancer treatment and TA can serve as a therapeutic agent for this
      devastating disease.

PMID- 19851712
TI  - Metabolism, pharmacokinetics and pharmacodynamics of the factor Xa inhibitor
      apixaban in rabbits.
AB  - Apixaban has similar affinity for human and rabbit factor Xa (FXa). Rabbits are
      commonly used in development of thrombosis disease models; however, unlike in
      other species, apixaban demonstrated poor oral bioavailability (F = 3%) and a
      high clearance rate (2.55 l/h/kg) in rabbits. Oxidative metabolism of [14C]
      apixaban by liver microsomes was approximately 20 times faster in rabbits than in
      rats or humans. Following an intravenous (IV) dose of 5 mg/kg, circulating levels
      of [14C] apixaban decreased from the earliest sampling time (5 min) to
      undetectable at 4 h. After an oral dose of 30 mg/kg, levels of [14C] apixaban
      were only detected at 1 and 4 h. Radioactivity profiling showed that apixaban was
      a significant component in plasma only after IV administration; O-demethyl
      apixaban (M2), O-demethyl apixaban glucuronide (M14) and O-demethyl apixaban
      sulfate (M1) were prominent metabolites after both IV and oral administration.
      Studies of apixaban in rabbits showed a good correlation between apixaban
      concentrations and inhibition of FXa activity, prolongation of prothrombin time
      and modified prothrombin time, with no lag time between these ex vivo
      pharmacodynamic markers and plasma drug levels. The apixaban concentration
      required for 50% inhibition (IC50) of FXa activity ex vivo (0.22 +/- 0.02 microM)
      agreed with the IC50 from in vitro experiments in rabbit and human plasma. In
      summary, apixaban shows similar affinity for human and rabbit FXa. It produces a
      rapid onset of action, predictable concentration-dependent pharmacodynamic
      responses, and, unlike rats or humans, a rapid hepatic metabolism in rabbits.

PMID- 19851713
TI  - Aliasing in reduced dimensionality NMR spectra: (3,2)D HNHA and (4,2)D HN(COCA)NH
      experiments as examples.
AB  - Reduced dimensionality NMR spectra usually require very large spectral widths in
      the shared dimension. In this paper we show that aliasing can be introduced in
      reduced dimensionality NMR spectra either to decrease the acquisition time or
      increase the resolution of the experiments without losing information. The gains
      of introducing aliasing are illustrated with two examples, the (3,2)D HNHA and
      the (4,2)D HN(COCA)NH experiments. In both cases a reduction of the spectral
      width of more than 50% was possible.

PMID- 19851714
TI  - Controversies in cancer stem cells.

PMID- 19851715
TI  - Monash at the academic industrial interface: trains and platforms.

PMID- 19851716
TI  - [Minimally invasive plate osteosynthesis on the proximal upper limb. Instructions
      for surgery].

PMID- 19851717
TI  - [Current status of minimally invasive plate osteosynthesis: specific part II].
AB  - With the increasing use of minimally invasive plate osteosynthesis in the last
      years almost every anatomical region was included in this new technique. Thus, it
      is not used any more for certain fractures and problematic areas, but also in
      fractures where it represents a challenge to established osteosynthesis
      techniques like intramedullary nailing or conventional plating. Therefore the
      challenge for the treating surgeon increased to find the right answer for the
      particularities of an individual fracture by choosing the optimal method. The
      most popular indications for the use of minimally invasive plate osteosynthesis
      are presented and the technical details are discussed. The possibilities for
      complications--in a common way and for specific fractures--are presented and
      discussed.

PMID- 19851718
TI  - Mice lacking multidrug resistance protein 1a show altered dopaminergic responses
      to methylenedioxymethamphetamine (MDMA) in striatum.
AB  - Multidrug resistance protein 1a (MDR1a) potentiated methylenedioxymethamphetamine
      (MDMA)-induced decreases of dopamine (DA) and dopamine transport protein in mouse
      brain one week after MDMA administration. In the present study, we examined if
      mdr1a wild-type (mdr1a +/+) and knock-out (mdr1a -/-) mice differentially handle
      the acute effects of MDMA on the nigrostriatal DA system 0-24 h following a
      single drug injection. 3-way ANOVA revealed significant 2-way interactions of
      strain x time (F (5,152) = 32.4, P < 0.001) and strain x dose (F (3,152) = 25.8,
      P < 0.001) on 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratios in mdr1a +/+ and 
      /- mice. 0.3-3 h after 10 mg/kg MDMA, DOPAC/DA ratios were increased in mdr1a +/+
      mice, but decreased 0.3-1 h after MDMA in mdr1a -/- mice. Twenty-four hours after
      10 mg/kg MDMA, DOPAC/DA ratios were increased 600% in mdr1a +/+ mice compared to
      saline-treated control mice, while in mdr1a -/- mice DOPAC/DA ratios were
      unchanged. Striatal MDMA and its metabolite, methylenedioxyamphetamine,
      concentrations by gas chromatography-mass spectrometry were similar in both
      strains 0.3-4 h after MDMA, discounting the role of MDR1a-facilitated MDMA
      transport in observed inter-strain differences. Increased DOPAC/DA turnover in
      mdr1a +/+ mice following MDMA is consistent with the previous report that MDMA
      neurotoxicity is increased in mdr1a +/+ mice. Increased DA turnover via monoamine
      oxidase in mdr1a +/+ vs -/- mice might increase exposure to neurotoxic reactive
      oxygen species.

PMID- 19851719
TI  - Mechanism of the specific neuronal toxicity of a type I ribosome-inactivating
      protein, trichosanthin.
AB  - The aim was to study the mechanism of neuronal toxicity, the cellular pathway,
      and the glial cell reactions induced by trichosanthin (TCS), a type I ribosome
      inactivating protein (RIP). Ricin A chain (RTA) was included for comparison. TCS,
      RTA, and fluorescein isothiocyanate (FITC)-labeled TCS and RTA were separately
      injected into rat eyes. Saline or pure FITC was used as the control. Electron
      microscopy, confocal microscopy, and lectin and immunohistochemical staining were
      used to study the neurotoxic mechanism. TCS mainly induced apoptosis by causing
      degeneration of the mitochondria. TCS was able to enter the Muller and pigment
      cells. It caused a change in cell number of the following types of glial cells: a
      decrease in Muller cells, an increase in astrocytes, and little change in
      microglia. In contrast, RTA mainly induced necrosis and entered vascular
      endothelial cells. Astrocyte and microglia reactions were stronger in the RTA
      treated retinas than those in the TCS-treated retinas. In conclusion, TCS appears
      to selectively enter and destroy Muller and pigment epithelia cells, which
      subsequently induce the death of photoreceptors. Degeneration of mitochondria is
      involved in the pathways of apoptosis of the photoreceptors caused by TCS. In
      sharp contrast, RTA can enter vascular endothelial cells and damage the vascular
      endothelium, resulting in retinitis and necrosis.

PMID- 19851720
TI  - The immunogenicity of the liposome-associated outer membrane proteins (OMPs) of
      Moraxella catarrhalis.
AB  - The outer membrane proteins (OMPs) are the most immunogenic and attractive of the
      Moraxella catarrhalis vaccine antigens that may induce the protective immune
      response. The aim of this study was to determine the effectiveness of two types
      of OMP-associated phosphatidylcholine (PC) liposomal formulations (OMPs-PC, PC
      OMPs) and of Zwittergent-based proteomicelles (OMPs-Z) in potentiating an anti
      OMP systemic immune response in mice. The immunogenicities of the above
      preparations were evaluated by assessing serum anti-OMP IgG and IgA reactivity in
      the post-immunized mouse antisera using ELISA and Western blotting. Additionally,
      the cross-reactivity of the most effective anti-OMP response was determined using
      heterologous sera from both humans and mice. Both the proteoliposomes and the
      proteomicelles showed high immunogenic properties and did not elicit any distinct
      quantitative differences in the antibody titer or qualitative differences in the
      pattern of the mouse antisera. The post-immunized mouse antisera predominantly
      recognized a approximately 60-kDa OMP of M. catarrhalis. That protein was also
      found to be a highly cross-reactive antigen interacting with a panel of pooled
      mouse antisera produced by immunization either with whole cells or the purified
      OMPs of heterologous M. catarrhalis strains. Furthermore, normal sera collected
      from healthy children were found to be preferentially reactive with the 60-kDa
      OMP. The serum-specific IgG, IgA and IgM were respectively detected via
      immunoblotting in 90%, 85% and 30% of heterologous human sera. This similar
      immunogenic effectiveness of both OMP-associated liposomal formulations could
      contribute to the practical use of such formulations in the future in human
      vaccination. Moreover, the highly cross-reactive 60-kDa OMP seems to be an
      important antigenic marker of M. catarrhalis, and, as it is responsible for the
      induction of an antibody-mediated and long-lasting immune response, studying it
      may partially aid us in understanding the relatively low degree of pathogenicity
      of the bacterium in immunocompetent individuals.

PMID- 19851721
TI  - Lead and arsenic levels in women with different body mass composition.
AB  - The objective of this study was to evaluate whether lead (Pb) and arsenic (As)
      levels in biological fluids were associated to the body composition in a group of
      reproductive-age women. Voluntary childbearing-age women (n = 107) were divided
      into three groups according to their body mass index (BMI: weight/height(2)
      (kg/m(2)): low weight (BMI<18.5 kg/m(2)), normal (BMI > 19 < 24.9 kg/m2), and
      overweight (BMI>25 kg/m(2)). Body composition and fat mass percentage were
      determined by the isotopic dilution method utilizing deuterated water. Blood lead
      concentrations were determined by graphite furnace atomic absorption spectrometry
      and urinary arsenic (AsU) concentrations by inductively coupled plasma mass
      spectrometry. The type and frequency of food consumption and lifestyle-related
      factors were also registered. Most women had PbB levels > 2 < 10MU g/dl, and only
      2.6% had AsU concentrations above 50 microg/L. The levels of these toxic elements
      were not found to be associated with the fat mass percentage.

PMID- 19851722
TI  - Antarcticimonas flava gen. nov., sp. nov., isolated from Antarctic coastal
      seawater.
AB  - A marine bacterium, designated IMCC3175(T), was isolated from a seawater sample
      collected off the Antarctic coast. The strain was Gram-negative, obligately
      aerobic, carotenoid pigment-containing, and rod-shaped bacterium that divided by
      binary fission. As determined by 16S rRNA gene sequence comparisons, the most
      closely related genera were Formosa (92.9 approximately 93.3%), Bizionia (91.6
      approximately 93.2%), Gaetbulibacter (91.5 approximately 92.8%), Sediminibacter
      (92.7%), Yeosuana (92.6%), Subsaximicrobium (92.1 approximately 92.2%), and
      Gillisia (89.5 approximately 92.2%). Phylogenese analysis based on 16S rRNA gene
      sequences showed that the strain formed a monophyletic clade together with the
      genera Sediminibacter and Subsaximicrobium but represented an independent
      phyletic line in this clade of the family Flavobacteriaceae. The DNA G+C content
      of the strain was 37.3 mol%. The major respiratory quinone was MK-6 and the
      predominant cellular fatty acids were C(16:1) omega7c and/or iso-C(15:0) 2-OH
      (12.8%), anteiso-C(15:0) (9.4%), and iso-C(16:1) (9.4%). Low 16S rRNA gene
      sequence similarity, formation of a distinct phylogenetic branch, and several
      phenotypic characteristics, including a narrow range of temperature and salinity
      for growth, differentiated strain IMCC3175(T) from other related genera in the
      family Flavobacteriaceae. Therefore the name Antarcticimonas flava gen. nov., sp.
      nov. is proposed, with strain IMCC3175(T) (=KCCM 42713(T) =NBRC 103398(T)) as the
      type strain.

PMID- 19851723
TI  - Paenibacillus filicis sp. nov., isolated from the rhizosphere of the fern.
AB  - A Gram-positive and endospore-forming bacterial strain, designated S4(T), was
      isolated from the rhizosphere of ferns in Daejeon, Republic of Korea. This
      isolate is strictly aerobic, motile, and rod-like in shape, and it is positive
      for catalase, oxidase, esterase lipase, and beta-galactosidase activities. In
      addition, this strain grows when cultured at temperatures between 15 and 37
      degrees C and at pH values ranging from 5.5 to 9.0. The DNA G+C content was
      determined to be 53.2 mol%. Strain S4(T) has meso-diaminopimelic acid in the cell
      wall peptidoglycan; it also contains menaquinone 7 (MK-7) as the predominant
      isoprenoid quinone and anteiso-C(15:0) (57.5%), iso-C(16:0) (11.3%), and C(16:0)
      (9.4%) as the major cellular fatty acids. Phylogenetic analysis based on
      alignments of the 16S rRNA gene sequence showed that S4(T) is affiliated with a
      cluster of strains within the genus Paenibacillaceae and is most closely related
      to Paenibacillus chinjuensis WN9(T), with 96.8% similarity. Based on the
      phylogenetic and phenotypic characteristics of strain S4(T), we believe that this
      isolate should be distinguished from all type species of the genus Paenibacillus
      and should thus represent a novel taxon within the genus Paenibacillus. We
      propose naming this type species Paenibacillus filicis sp. nov. for the
      rhizosphere isolate; the type strain will be known as S4(T) (=KCTC 13693(T) =KACC
      14197(T) =JCM 16417(T)).

PMID- 19851724
TI  - Paenibacillus pinihumi sp. nov., a cellulolytic bacterium isolated from the
      rhizosphere of Pinus densiflora.
AB  - A novel cellulolytic bacterium, strain S23(T), was isolated from the rhizosphere
      of the pine trees in Daejeon, Republic of Korea. This isolate was Gram-positive,
      strictly aerobic, rod-shaped, catalase-negative, oxidase-positive, motile by
      means of peritrichous flagella, and tested positive for alkaline phosphatase,
      esterase lipase, leucine arylamidase, alpha-galactosidase, and beta-galactosidase
      activities. The DNA G+C content was 49.5 mol%. The main cellular fatty acids were
      anteiso-C(15:0) (51.9%), iso-C(16:0) (14.7%), and iso-C(15:0) (13.2%). The major
      isoprenoid quinone was menaquinone 7 (MK-7). Diagnostic diamino acid in the cell
      wall pepti-doglycan was meso-diaminopimelic acid. Comparative 16S rRNA gene
      sequence analysis showed that this strain clustered with Paenibacillus species.
      The 16S rRNA gene sequence similarity values between S23(T) and other
      Paenibacillus species were between 89.9% and 95.9%, and S23(T) was most closely
      related to Paenibacillus tarimensis SA-7-6(T). On the basis of phylogenetic and
      phenotypic properties of strain S23(T), the isolate is considered as a novel
      species belonging to the genus Paenibacillus. Therefore, the name, Paenibacillus
      pinihumi sp. nov., is proposed for the rhizosphere isolate; the type strain is
      S23(T) (=KCTC 13695(T) =KACC 14199(T) =JCM 16419(T)).

PMID- 19851725
TI  - Nitroreductase II involved in 2,4,6-trinitrotoluene degradation: purification and
      characterization from Klebsiella sp. Cl.
AB  - Three 2,4,6-trinitrotoluene (TNT) nitroreductases from Klebsiella sp. CI have
      different reduction capabilities that can degrade TNT by simultaneous utilization
      of two initial reduction pathways. Of these, nitroreductase II was purified to
      homogeneity by sequential chromatographies. Nitroreductase II is an oxygen
      insensitive enzyme and reduces both TNT and nitroblue tetrazolium. The N-terminal
      amino acid sequence of the enzyme did not show any sequence similarity with those
      of other nitroreductases reported. However, it transformed TNT by the reduction
      of nitro groups like nitroreductase I. It had a higher substrate affinity and
      specific activity for TNT reduction than other nitroreductases, and it showed a
      higher oxidation rate of NADPH with the ortho-substituted isomers of TNT
      metabolites (2-hydroxylaminodinitrotoluene and 2-aminodinitrotoluene) than with
      para-substituted compounds (4-hydroxylaminodinitrotoluene and 4-amino
      dinitrotoluene).

PMID- 19851726
TI  - Characterization of a novel beta-glucosidase-like activity from a soil
      metagenome.
AB  - We report the cloning of a novel beta-glucosidase-like gene by function-based
      screening of a metagenomic library from uncultured soil microorganisms. The gene
      was named bgllC and has an open reading frame of 1,443 base pairs. It encodes a
      481 amino acid polypeptide with a predicted molecular mass of about 57.8 kDa. The
      deduced amino acid sequence did not show any homology with known beta
      glucosidases. The putative beta-glucosidase gene was subcloned into the pETBlue-2
      vector and overexpressed in E. coli Tuner (DE3) pLacI; the recombinant protein
      was purified to homogeneity. Functional characterization with a high performance
      liquid chromatography method demonstrated that the recombinant BgllC protein
      hydrolyzed D-glucosyl-beta-(l-4)-D-glucose to glucose. The maximum activity for
      BgllC protein occurred at pH 8.0 and 42 degrees C using p-nitrophenyl-beta-D
      glucoside as the substrate. A CaCl(2) concentration of 1 mM was required for
      optimal activity. The putative beta-glucosidase had an apparent K(m) value of
      0.19 mM, a V(max) value of 4.75 U/mg and a k (cat) value of 316.7/min under the
      optimal reaction conditions. The biochemical characterization of BgllC has
      enlarged our understanding of the novel enzymes that can be isolated from the
      soil metagenome.

PMID- 19851727
TI  - Analysis and identification of ADP-ribosylated proteins of Streptomyces
      coelicolor M145.
AB  - Mono-ADP-ribosylation is the enzymatic transfer of ADP-ribose from NAD(+) to
      acceptor proteins catalyzed by ADP-ribosyltransferases. Using m
      aminophenylboronate affinity chromatography, 2D-gel electrophoresis, in-gel
      digestion and MALDI-TOF analysis we have identified eight in vitro ADP
      ribosylated proteins in Streptomyces coelicolor, which can be classified into
      three categories: (i) secreted proteins; (ii) metabolic enzymes using NAD(+)/NADH
      or NADP(+)/NADPH as coenzymes; and (iii) other proteins. The secreted proteins
      could be classified into two functional categories: SCO2008 and SC05477 encode
      members of the family of periplasmic extracellular solute-binding proteins, and
      SCO6108 and SC01968 are secreted hydrolases. Dehydrogenases are encoded by
      SC04824 and SC04771. The other targets are GlnA (glutamine synthetase I.,
      SC02198) and SpaA (starvation-sensing protein encoded by SC07629). SCO2008
      protein and GlnA had been identified as ADP-ribosylated proteins in previous
      studies. With these results we provided experimental support for a previous
      suggestion that ADP-ribosylation may regulate membrane transport and localization
      of periplasmic proteins. Since ADP-ribosylation results in inactivation of the
      target protein, ADP-ribosylation of dehydrogenases might modulate crucial primary
      metabolic pathways in Streptomyces. Several of the proteins identified here could
      provide a strong connection between protein ADP-ribosylation and the regulation
      of morphological differentiation in S. coelicolor.

PMID- 19851728
TI  - Overexpression of outer membrane protein OprT and increase of membrane
      permeability in phoU mutant of toluene-tolerant bacterium Pseudomonas putida
      GM730.
AB  - Eight toluene-sensitive mutants were previously isolated from the toluene
      tolerant bacterium Pseudomonas putida GM730. One of these mutants was TOS6, in
      which Tn5 had been inserted into phoU. Susceptibility to multiple antibiotics, as
      well as toluene sensitivity, was increased in the phoU mutant of P. putida GM730.
      We compared the outer membrane proteins from the phoU mutant and wild-type via
      two-dimensional gel electrophoresis. A 45 kDa protein was dramatically
      overexpressed as the result of phoU inactivation, and this protein was identified
      by peptide mass fingerprinting and microsequencing as a conserved hypothetical
      protein consisting of 414 amino acids. The protein, designated as OprT, harbors a
      signal sequence and extended beta-sheets, both of which are features common to
      the bacterial porins. The rate of ethidium bromide accumulation in TOS6 was
      higher than in GM730, which indicates that the TOS6 membranes may be more
      permeable to ethidium bromide than are the membranes of GM730. We propose that
      the toluene sensitivity and increased antibiotic susceptibility observed in the
      phoU mutant may be attributable to increased membrane permeability.

PMID- 19851729
TI  - Response surface analysis for the production of an enantioselective lipase from
      Aspergillus niger by solid-state fermentation.
AB  - The lipase produced by the Aspergillus niger strain AC-54 has been widely studied
      due to its enantioselectivity for racemic mixtures. This study aimed to optimize
      the production of this enzyme using statistical methodology. Initially a Plackett
      Burman (PB) design was used to evaluate the effects of the culture medium
      components and the culture conditions. Twelve factors were screened: water
      content, glucose, yeast extract, peptone, olive oil, temperature, NaH(2)P0(4),
      KH(2)P0(4), MgS0(4)-7H(2)0, CaCl(2), NaCI, and MnS0(4). The screening showed that
      the significant factors were water content, glucose, yeast extract, peptone,
      NaH(2)P0(4), and KH(2)P0(4), which were optimized using response surface
      methodology (RSM) and a mathematical model obtained to explain the behavioral
      process. The best lipase activity was attained using the following conditions:
      water content (20%), glucose (4.8%), yeast extract (4.0%), and NaH2P04 (4.0%).
      The predicted lipase activity was 33.03 U/ml and the experimental data confirmed
      the validity of the model. The enzymatic activity was expressed as micromoles of
      oleic acid released per minute of reaction (micromol/min).

PMID- 19851730
TI  - Ligand-receptor recognition for activation of quorum sensing in Staphylococcus
      aureus.
AB  - The accessory gene regulator (agr) locus controls many of the virulence toxins
      involved in Staphylococcus aureus pathogenesis, and can be divided into four
      specificity groups. AgrC is the only group-specific receptor to mediate both
      intra-group activation and inter-group inhibition. We studied the ligand-receptor
      recognition of the agr system in depth by using a luciferase reporter system to
      identify the key residues responsible for AgrC activation in two closely related
      agr groups, AgrC-I, and AgrC-IV. Fusion PCR and site-directed mutagenesis were
      used to screen for functional residues of AgrC. Our data suggest that for AgrC-IV
      activation, residue 101 is critical for activating the receptor. In contrast, the
      key residues for the activation of AgrC-I are located at residues 49
      approximately 59, 107, and 116. However, three residue changes, T101A, V107S,
      I116S, are sufficient to convert the AIP recognizing specificity from AgrC-IV to
      AgrC-I.

PMID- 19851731
TI  - Development and validation of a recombinant nucleocapsid protein-based ELISA for
      detection of the antibody to porcine reproductive and respiratory syndrome virus.
AB  - Three indirect enzyme-linked immunosorbent assays (iELISA) based on the North
      American like (NA-like), European like (EU-like) and co-expressed NA- and EU-like
      recombinant nucleocapsid proteins (N-protein) of porcine reproductive and
      respiratory syndrome virus (PRRSV) were validated for the detection of the
      antibodies in porcine sera. A total of 422 serum samples from unvaccinated pigs
      were tested. The cut-off value was optimized by a two-graph receiver operating
      characteristics analysis at a 95% confidence level. This assay was validated with
      Western blot analysis and IDEXX HerdChek ELISA. Cross-reactivity results showed
      that iELISA was PRRSV-specific. Repeatability tests revealed that the
      coefficients of variation of positive sera within and between runs were less than
      10%. The results indicate that iELISA is simpler to produce and perform, time
      saving and suitable for large scale surveys of PRRSV infection at low cost, and
      is potentially useful to evaluate the efficiency of various vaccines against
      PRRSV.

PMID- 19851732
TI  - Identification of a novel linear B-cell epitope in the M protein of avian
      infectious bronchitis coronaviruses.
AB  - This report describes the identification of a novel linear B-cell epitope at the
      C-terminus of the membrane (M) protein of avian infectious bronchitis virus
      (IBV). A monoclonal antibody (MAb) (designated as 15E2) against the IBV M protein
      was prepared and a series of 14 partially-overlapping fragments of the IBV M gene
      were expressed with a GST tag. These peptides were subjected to enzyme-linked
      immunosorbent assay (ELISA) and western blotting analysis using MAb 15E2 to
      identify the epitope. A linear motif, (199)FATFVYAK(206), which was located at
      the C-terminus of the M protein, was identified by MAb 15E2. ELISA and western
      blotting also showed that this epitope could be recognized by IBV-positive serum
      from chicken. Given that 15E2 showed reactivity with the (199)FATFVYAK(206)
      motif, expressed as a GST fusion protein, in both western blotting and in an
      ELISA, we proposed that this motif represented a linear B-cell epitope of the M
      protein. The (199)FATFVYAK(206) motif was the minimal requirement for reactivity
      as demonstrated by analysis of the reactivity of 15E2 with several truncated
      peptides that were derived from the motif. Alignment and comparison of the 15E2
      defined epitope sequence with the sequences of other corona-viruses indicated
      that the epitope is well conserved among chicken and turkey coronaviruses. The
      identified epitope should be useful in clinical applications and as a tool for
      the further study of the structure and function of the M protein of IBV.

PMID- 19851733
TI  - Production of and applications for a polyclonal IgY diagnostic reagent specific
      for Mycobacterium avium subsp. paratuberculosis.
AB  - Antibodies specific to the cell surface antigens of Mycobacterium avium subsp.
      paratuberculosis (MAP) have multiple useful applications, e.g. organism
      detection, immunoconcentration, and cell visualization. The aim of this study was
      to produce and compare polyclonal antibodies for such research and diagnostic
      purposes. Three polyclonal antibodies to MAP were produced using sera from
      immunized rabbits and chickens plus naturally infected cows. Cross-reactive
      antibodies in each MAP antibody preparation were removed by absorption with
      heterologous mycobacterial and non-mycobacterial cells. The specificity of each
      resulting polyclonal antibody preparation was evaluated by ELISA to multiple
      bacterial cell wall extract antigens. After absorption, chicken anti-MAP IgY had
      the highest specificity of the three antibody preparations. FITC-la-beled anti
      MAP IgY was used to effectively locate MAP in macrophages 12 h post-infection.
      Also, immunomagnetic beads coated with anti-MAP IgY enhanced recovery of MAP from
      bacterial suspensions in comparison with non-antibody coated beads. Anti-MAP IgY
      provides a novel new reagent with broad diagnostic and research applications
      requiring specific concentration, detection, and quantification of MAP.

PMID- 19851734
TI  - Identification and characterization of a novel antibacterial peptide, avian beta
      defensin 2 from ducks.
AB  - In this study, a novel avian beta-defensin (AvBD) was isolated from duck
      pancreas. The complete nucleotide sequence of the gene contained an 195 bp open
      reading frame encoding 64 amino acids. Homology, characterization and comparison
      of the gene with AvBD from other avian species confirmed that it was duck AvBD2.
      The mRNA expression of the gene was analyzed in 17 tissues from 21-day-old ducks.
      AvBD2 was highly expressed in the trachea, crop, heart, bone marrow, and
      pancreas; moderately expressed in the muscular stomach, small intestine, kidney,
      spleen, thymus, and bursa of Fabricius; and weakly expressed in skin. We produced
      and purified recombinant AvBD2 by expressing the gene in Escherichia coli. As
      expected, the recombinant peptide exhibited strong bactericidal properties
      against Bacillus cereus, Staphylococcus aureus, and Pasteurella multocida, and
      weak bactericidal properties against E. coli and Salmonella choleraesuis. In
      addition, the recombinant protein retained antimicrobial activity against S.
      aureus under different temperatures (range, -20 degrees C to 100 degrees C) and
      pH values (range, 3 to 12).

PMID- 19851735
TI  - The photodynamic effect of methylene blue and toluidine blue on Candida albicans
      is dependent on medium conditions.
AB  - Due to the increased number of immunocompromised patients, the infections
      associated with the pathogen of the genus Candida and other fungi have increased
      dramatically. Photodynamic antimicrobial chemotherapy (PACT) has been presented
      as a potential antimicrobial therapy, in a process that combines light and a
      photosensitizing drug, which promotes a phototoxic response by the treated cells.
      In this work, we studied the effects of the different medium conditions during
      PACT, using either methylene blue (MB) or toluidine blue (TB) on Candida
      albicans. The inhibition of the growth produced by PACT was decreased for
      different pH values (6.0, 7.0, and 8.0) in a buffered medium. The phototoxic
      effects were observed only in the presence of saline (not buffered medium). PACT
      was modulated by calcium in a different manner using either MB or TB. Also when
      using MB both verapamil or sodium azide were able to decrease the phototoxic
      effects on the C. albicans. These results show that PACT is presented as a new
      and promising antifungal therapy, however, new studies are necessary to
      understand the mechanism by which this event occurs.

PMID- 19851736
TI  - Identification of the Vibrio vulnificus ahpCl gene and its influence on survival
      under oxidative stress and virulence.
AB  - Pathogens have evolved sophisticated mechanisms to survive oxidative stresses
      imposed by host defense systems, and the mechanisms are closely linked to their
      virulence. In the present study, ahpCl, a homologue of Escherichia coli ahpC
      encoding a peroxiredoxin, was identified among the Vibrio vulnificus genes
      specifically induced by exposure to H(2)O(2). In order to analyze the role of
      AhpCl in the pathogenesis of V. vulnificus, a mutant, in which the ahpCl gene was
      disrupted, was constructed by allelic exchanges. The ahpCl mutant was
      hypersusceptable to killing by reactive oxygen species (ROS) such as H(2)O(2) and
      t-BOOH, which is one of the most commonly used hydroperoxides in vitro. The
      purified AhpCl reduced H(2)O(2) in the presence of AhpF and NADH as a hydrogen
      donor, indicating that V. vulnificus AhpCl is a NADH-dependent peroxiredoxin and
      constitutes a peroxide reductase system with AhpF. Compared to wild type, the
      ahpCl mutant exhibited less cytotoxicity toward INT-407 epithelial cells in vitro
      and reduced virulence in a mouse model. In addition, the ahpCl mutant was
      significantly diminished in growth with INT-407 epithelial cells, reflecting that
      the ability of the mutant to grow, survive, and persist during infection is also
      impaired. Consequently, the combined results suggest that AhpCl and the
      capability of resistance to oxidative stresses contribute to the virulence of V.
      vulnificus by assuring growth and survival during infection.

PMID- 19851738
TI  - Prediction of bacterial proteins carrying a nuclear localization signal and
      nuclear targeting of HsdM from Klebsiella pneumoniae.
AB  - Nuclear targeting of bacterial proteins is an emerging pathogenic mechanism
      whereby bacterial proteins can interact with nuclear molecules and alter the
      physiology of host cells. The fully sequenced bacterial genome can predict
      proteins that target the nuclei of host cells based on the presence of nuclear
      localization signal (NLS). In the present study, we predicted bacterial proteins
      with the NLS sequences from Klebsiella pneumoniae by bioinformatic analysis, and
      13 proteins were identified as carrying putative NLS sequences. Among them, HsdM,
      a subunit of KpnAl that is a type I restriction-modification system found in K.
      pneumoniae, was selected for the experimental proof of nuclear targeting in host
      cells. HsdM carried the NLS sequences, (7)KKAKAKK(13), in the N-terminus. A
      transient expression of HsdM-EGFP in COS-1 cells exhibited exclusively a nuclear
      localization of the fusion proteins, whereas the fusion proteins of HsdM with
      substitutions in residues lysine to alanine in the NLS sequences, (7)AAAKAAA(13),
      were localized in the cytoplasm. HsdM was co-localized with importin o in the
      nuclei of host cells. Recombinant HsdM alone methylated the eukaryotic DNA in
      vitro assay. Although HsdM tested in this study has not been considered to be a
      virulence factor, the prediction of NLS motifs from the full sequenced genome of
      bacteria extends our knowledge of functional genomics to understand subcellular
      targeting of bacterial proteins.

PMID- 19851737
TI  - Comparative analysis of immune responses to Mycobacterium abscessus infection and
      its antigens in two murine models.
AB  - Mycobacterium abscessus has been identified as an emerging pulmonary pathogen in
      humans. Because little is known regarding immune responses elicited by M.
      abscessus or its antigens, immunological responses were studied in two murine
      models subjected to intravenous (high-dose or systemic infection) or pulmonary
      (low-dose or local infection) inoculation with M. abscessus ATCC 19977. An
      overall comparison between the two models showed similar patterns of bacterial
      survival and host immune responses. The colonization of M. abscessus was the
      highest at 5 days post-infection (dpi) and its elimination was positively
      correlated with cell-mediated immunity in both challenges. However, an inverse
      relationship was observed between progressive inflammation and mycobacterial
      colonization levels in mice infected with a high dose at 14 dpi. Regarding
      antigens, culture filtrate (CF) of M. abscessus strongly induced IFN-gamma
      secretion, whereas cellular extract (CE) antigen elicited strong antibody
      responses. The antibody response to M. abscessus antigens in mice subjected to
      low-dose infection increased when the cellular immune response decreased over 14
      dpi. However, the antibody response for the high-dose infection increased
      promptly after the infection. In comparison of cytokine expression in lung
      homogenates after M. abscessus infection, Thl and Th2 cytokines increased
      simultaneously in the high-dose infection, whereas only cell-mediated immunity
      developed in the low-dose pulmonary infection. These findings not only enhance
      our understanding of the immune response to M. abscessus infection according to
      systemic or pulmonary infection, but may also aid in immunological diagnosis and
      vaccine development. M. abscessus, murine infection model, immune response,
      antigens, cytokines.

PMID- 19851739
TI  - Development of a method based on surface enhanced laser desorption and ionization
      time of flight mass spectrometry for rapid identification of Klebsiella
      pneumoniae.
AB  - A method based on surface enhanced laser desorption and ionization time of flight
      mass spectrometry (SELDI-TOF MS) was developed for the rapid identification of
      Klebsiella pneumoniae by directly applying bacterial colonies without further
      protein extraction. A total of 40 K. pneumoniae and 114 other related
      microorganisms isolated clinically were analyzed by SELDI-TOF MS. An
      identification model for K. pneumoniae was established by artificial neural
      networks (ANNs) with classification accuracy of 100%. The model was blindly
      tested with 43 K. pneumoniae and 53 control bacteria again. The results showed
      that the model was successful with accuracy of 96.9%, sensitivity of 100% and
      specificity of 943%. This strategy is potential for rapid identification of K.
      pneumoniae.

PMID- 19851740
TI  - Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolyesters with a
      high molar fraction of 3-hydroxyvalerate by an insect-symbiotic Burkholderia sp.
      IS-01.
AB  - Burkholderia sp. IS-01 capable of biosynthesizing poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) [poly(3HB-co-3HV)] copolyesters with a high molar fraction of
      3HV was isolated from the gut of the adult longicorn beetle, Moechotypa diphysis.
      The strain IS-01 was relatively tolerant to high concentrations of levulinic acid
      and accumulated a poly(13.5 mol% 3HB-co-86.5 mol% 3HV) copolyester when
      cultivated on a mixture of gluconate (20 g/L) and levulinic acid (12.5 g/L). In
      this case, the content of the copolyester in the cells was approximately 60.0%.
      The compositions of the copolyesters were easily regulated by altering the molar
      ratio of gluconate and levulinic acid in the medium. The organism was found to
      possess a class I PHA synthase (PhaC) gene (1,881 bp) that encodes a protein with
      a deduced molecular mass of 68,538 Da that consists of 626 amino acids. The PhaC
      of this organism was most similar to that of B. cenocepacia PC184 (92%
      similarity).

PMID- 19851741
TI  - Evidence against the physiological role of acetyl phosphate in the
      phosphorylation of the ArcA response regulator in Escherichia coli.
AB  - The Arc two-component signal transduction system of Escherichia coli comprises
      the ArcB sensor kinase and the ArcA response regulator. Under anoxic growth
      conditions, ArcB autophosphorylates and transphos-phorylates ArcA, which, in
      turn, represses or activates its target operons. ArcA has been shown to be able
      to autophosphorylate in vitro at the expense of acetyl-P. Here, the in vivo
      effect of acetyl phosphate on the redox signal transduction by the Arc system was
      assessed. Our results indicate that acetyl phosphate can modulate the expression
      of ArcA-P target genes only in the absence of ArcB. Therefore, the acetyl
      phosphate dependent ArcA phosphorylation route does not seem to play a
      significant role under physiological conditions.

PMID- 19851742
TI  - [On the efficacy of long-term psychodynamic psychotherapy for complex
      psychological disorders].
AB  - Rief and Hofmann (Nervenarzt 80:593-597) criticize in a very detailed comment our
      meta-analysis of long-term psychodynamic psychotherapy (JAMA 300:1551-1565).
      Although our article clearly included information that our meta-analysis
      addressed long-term psychodynamic psychotherapy of at least 50 sessions or at
      least 1 year duration, Rief and Hofmann allege that we studied "psychoanalysis"
      or "long-term psychoanalysis". Then they "show" for some of the studies we
      included that these studies did not address "psychoanalysis" or "long-term
      psychoanalysis" - which they did indeed not, but had never been claimed by us.
      For all other points of criticism put forward by the authors we show that they
      are not tenable as well. In addition, we show that Rief and Hofmann use omissions
      and allegations that give the impression that we deliberately violated principles
      of good scientific practice. This is reputation-damaging behaviour that clearly
      goes beyond a scientific discussion among researchers and constitutes a special
      act which itself violates the principles of good scientific practice.

PMID- 19851743
TI  - [Wilson's disease and multiple sclerosis. Co-occurrence].
AB  - Wilson's disease is a rare autosomal recessive disorder of hepatic copper
      transport leading to hepatic but also to highly variable neurological symptoms
      with basal ganglia and cerebellar manifestation. Symptoms, signs and results of
      investigations can overlap with those of other central nervous system disorders
      such as multiple sclerosis and sometimes delay diagnosis.We report on a 38-year
      old male patient who was diagnosed with a hepatic form of Wilson's disease at age
      12 and with multiple sclerosis at age 38. Intravenous radio copper test confirmed
      the diagnosis of Wilson's disease. Multiple sclerosis was diagnosed after
      occurrence of transient sensory disturbances in both legs, based on typical
      changes on MRI over the course of 2 years, in the cerebrospinal fluid and in
      multimodal evoked potentials.Although Wilson's disease and multiple sclerosis are
      known as distinct diseases with a completely different pathophysiology, symptoms
      and results of evoked potentials overlap, and they share a common historic
      background. Similarities and differences of both disorders are discussed.

PMID- 19851744
TI  - [Psychiatry over the course of life].

PMID- 19851745
TI  - [Options, limits and ethics of pharmacological neuroenhancement].
AB  - Pharmacological neuroenhancement is an attempt to increase cognitive performance
      in healthy humans. Learning and memory, attention and vigilance or mood and
      social interaction are targeted by a modulation of brain plasticity. Firstly, an
      analysis of the current state of research shows that, until now, clinical trials
      of neuroenhancing drugs have demonstrated only limited efficacy and long-term
      side effects remain largely unexplored. Secondly, we argue that, from an ethical
      perspective, neuroenhancement differs from socially mediated methods of learning.
      Pharmacological neuroenhancement is based on notions of efficacy and control that
      threaten to undermine other important aspects of mental capacities.

PMID- 19851746
TI  - [Hemodialysis fistulas: possibilities of vascular ultrasound].
AB  - Vascular ultrasound is an established technique in shunt diagnostics for
      hemodialysis fistulas that allows non-invasive diagnosis of vascular morphology
      and hemodynamics. Early detection of shunt stenoses in hemodialysis fistulas or
      thrombotic occlusions facilitates an interventional decision. High occlusion
      rates of up to 45% within 1 year in hemodialysis fistulas due to reduced flow
      volume justify follow up with vascular ultrasound examination. The use of high
      resolution transducers in vascular ultrasound enables complications, such as
      stenoses and occlusions to be recognized early therefore allowing preemptive
      therapy. In the present review the examination technique and strategy, the most
      important complications and treatment options will be discussed.

PMID- 19851747
TI  - [Pharmacological treatment of benign prostatic hyperplasia].
AB  - The majority of men with benign prostatic hyperplasia (BPH) seek medical help
      because of lower urinary tract symptoms (LUTS). Pharmacological treatment of BPH
      is indicated if the patient has no absolute indications for prostate surgery or
      benign prostatic obstruction (BPO), but LUTS with a decrease of quality of life.
      Plant extracts can be prescribed in men with mild to moderate symptoms. alpha
      Blockers can quickly and effectively decrease LUTS and symptomatic disease
      progression. If patients have predominantly bladder filling symptoms and a small
      prostate, muscarinic receptor antagonists are a viable treatment option. The
      combination of an alpha-blocker plus a muscarinic receptor antagonist is more
      effective than single drugs used alone. Especially in men with larger prostates,
      5alpha-reductase inhibitors can decrease LUTS and the probability of acute
      urinary retention as well as need for prostate surgery. The combination of alpha
      blocker plus 5alpha-reductase inhibitor can reduce LUTS and disease progression
      more effectively than single drugs.

PMID- 19851748
TI  - Single pancreatic beta cells co-express multiple islet hormone genes in mice.
AB  - AIMS/HYPOTHESIS: It is widely accepted that production of insulin, glucagon,
      somatostatin and pancreatic polypeptide in islet cells is specific to beta,
      alpha, delta and pancreatic polypeptide cells, respectively. We examined whether
      beta cells express other genes encoding islet hormones. METHODS: Nested RT-PCR
      was performed on single beta cells of transgenic mice with green fluorescent
      protein (GFP) driven by mouse insulin I promoter (MIP-GFP). RESULTS: Only 55% of
      adult beta cells expressed the insulin gene alone, while others expressed two or
      more islet hormone genes; 4% expressed all four hormone genes. In embryonic and
      neonatal cells, 60% to 80% of GFP(+) cells co-expressed pancreatic polypeptide
      and insulin genes in contrast to 29% in adult. To clarify cell fate, we conducted
      lineage tracing using rat insulin II promoter-cre mice crossed with reporter mice
      Gt(ROSA)26Sor-loxP-flanked STOP-cassette-GFP. All GFP(+) cells expressed insulin
      I and II genes, and showed similar heterogeneity of co-expression to that seen in
      MIP-GFP mice. Although we report expression of other hormone genes in a
      significant proportion of beta cells, our lineage tracing results demonstrate
      that after inducing InsII (also known as Ins2) expression, beta cell progenitors
      do not redifferentiate to non-beta cells. CONCLUSIONS/INTERPRETATION: This study
      shows co-expression of multiple hormone genes in beta cells of adult mice as well
      as in embryos and neonates. This finding could: (1) represent residual expression
      from beta cell precursors; (2) result from alternative developmental pathways for
      beta cells; or (3) denote the differentiation potential of these cells. It may be
      linked to functional heterogeneity. This heterogeneity in gene expression may
      provide a means to characterise the functional, cellular and developmental
      heterogeneity seen in beta cells.

PMID- 19851749
TI  - Mitogenic action of insulin: friend, foe or 'frenemy'?
AB  - Either endogenous or exogenous hyperinsulinaemia in the setting of insulin
      resistance promotes phosphorylation and activation of farnesyltransferase, a
      ubiquitous enzyme that farnesylates Ras proteins. Increased availability of
      farnesylated Ras at the plasma membrane enhances mitogenic responsiveness of
      cells to various growth factors, thus contributing to progression of cancer and
      atherosclerosis. This effect is specific to insulin, but is not related to the
      type of insulin used. The stimulatory effect of hyperinsulinaemia on
      farnesyltransferase in the presence of insulin resistance represents one
      potential mechanism responsible for mitogenicity and atherogenicity of insulin.

PMID- 19851750
TI  - [Tissue engineering of cartilage and bone : growth factors and signaling
      molecules].
AB  - Modern tissue engineering concepts integrate cells, scaffolds, signaling
      molecules and growth factors. In tissue engineering of cartilage, the growth
      plate of the long bone represents an interesting, well-organized developmental
      structure, with a spatial distribution of chondrocytes in different proliferation
      and differentiation stages embedded in a scaffold of extracellular matrix
      components. The proliferation and differentiation of these chondrocytes is
      regulated by various hormonal and paracrine factors. This article discusses some
      important growth factors in the process of endochondral ossification and
      demonstrates how this information could be translated into a controlled release
      system for different tissue engineering strategies.

PMID- 19851751
TI  - [Tissue engineering - state of the art and in future].

PMID- 19851752
TI  - Dilutional acidosis or uncovered cellular metabolism?

PMID- 19851753
TI  - Long-term patient satisfaction and functional outcome 8-11 years after
      subacromial decompression.
AB  - The aim of this investigation was to evaluate the long-term outcome of
      arthroscopic subacromial decompression (ASD) in patients with primary impingement
      syndrome stage II and early stage III. Ninety-five patients (105 shoulders, 48
      female), mean age 54 years (range 26-69), who had undergone surgery between 1996
      and 1999, were included. Pain intensity during activity and at rest, patient
      satisfaction, active range of motion (ROM), muscular strength and shoulder
      function using the Constant score were evaluated. Fifty-three (50%) shoulders
      were pain-free (Visual Analogue Scale < or = 10 mm) during activity and 72 (68%)
      shoulders were pain-free at rest. Sixty-one (58%) patients stated that they were
      very satisfied and 27 (25%) were quite satisfied with regard to their current
      shoulder function. Shoulders were divided into Group 1: Pain-free patients (n =
      53), Group 2: Patients with shoulder pain and no arthropathy (n = 41) and Group
      3: Patients with shoulder pain and arthropathy (n = 11). The groups had average
      active ROM of 157 degrees, 135 degrees and 117 degrees, respectively, in
      abduction and 97 degrees, 79 degrees, and 68 degrees in external rotation. The
      average strength in elevation in the scapular plane was 7.4, 5.8 and 3.9 kg,
      respectively, whereas the mean value in external rotation was 8.4, 7.9 and 5.3
      kg, respectively. The Constant score had a mean value of 87, 69 and 59 points in
      the three groups, respectively. Eleven shoulders have undergone re-operation, one
      after a new trauma. We conclude that ASD is a valuable procedure. Patients
      expressed a high degree of satisfaction with shoulder function 8-11 years after
      ASD.

PMID- 19851754
TI  - A 2-year follow-up of rehabilitation after ACL reconstruction using patellar
      tendon or hamstring tendon grafts: a prospective randomised outcome study.
AB  - Sixty-eight patients were clinically evaluated preoperatively, 3, 5, 7, 9 months,
      1 and 2 years after ACL reconstruction, 34 with patellar tendon graft, 34 with
      hamstring graft. Outcome regarding graft choice and anterior knee laxity (P =
      0.04) was in favour of patellar tendon graft. Hamstring graft led to a larger
      laxity, 2.4 mm compared with patellar tendon graft, 1.3 mm at 1 year and 2.5 mm
      and 1.5 mm, respectively, at 2 years (P = 0.05). There was a significant
      difference in rotational knee stability in favour of the patellar tendon graft at
      all test occasions but 9 months. A general effect regarding graft choice and
      muscle torque was found at 90 degrees/s for quadriceps (P = 0.03) and hamstrings
      (P < or = 0.0001) and at 230 degrees/s for hamstrings (P < or = 0.0001). No
      treatment effect regarding graft choice and one-leg hop test, postural sway or
      knee function was found. No group differences in anterior knee pain were found at
      any of the test occasions but 2 years in favour of hamstring graft compared to
      patellar tendon graft (P = 0.04). Patellar tendon graft resulted in higher
      activity level than hamstring graft at all test occasions but 1 year (P = 0.01).
      Patellar tendon ACL reconstruction led to more stable knees with less anterior
      knee laxity and less rotational instability than hamstring ACL reconstruction.
      Hamstring graft patients had not reached preoperative level in hamstring torque
      even 2 years after ACL reconstruction. Athletes with patellar tendon graft
      returned to sports earlier and at a higher level than those with hamstring graft.

PMID- 19851755
TI  - Postural orientation in subjects with anterior cruciate ligament injury:
      development and first evaluation of a new observational test battery.
AB  - Anterior cruciate ligament (ACL) injury is associated with mechanical instability
      and defective neuromuscular function, and can lead to further injury, increased
      joint loading and osteoarthritis. Patients with ACL injury demonstrate altered
      postural orientation, manifested as observable "substitution patterns" (SPs) but
      no one has applied a clinically useful method to systematically study postural
      orientation in these patients. Here, we investigated the presence of such
      patterns in 24 adults with ACL injury and in 49 controls, in parallel with the
      development and a first evaluation of a new test battery, test for SPs. The
      rationale behind the test for SPs was to characterize postural orientation as the
      ability to maintain appropriate relationships between body segments and
      environment during weight-bearing movements. In this first study, patients
      displayed SPs more frequently and/or more clearly on their injured, but also
      their uninjured side than did controls. Inter-rater and intra-rater
      reproducibility was good at a group level. Future studies of validity,
      responsiveness and including other subgroups of patients with ACL injury will
      have to prove if the test for SPs can be used in the diagnostics of defective
      neuromuscular function following knee injury, when planning and carrying out
      training and rehabilitation and when deciding appropriate time to return to
      activity and sports after ACL injury.

PMID- 19851756
TI  - Clinical and radiological outcomes of fixed- versus mobile-bearing total knee
      replacement: a meta-analysis.
AB  - Controversy exists regarding the clinical and radiological differences in
      outcomes between fixed- and mobile-bearing total knee replacements (TKR). The aim
      of this study was to compare these two TKR designs using a meta-analysis of the
      electronic databases MEDLINE, EMBASE, CINAHL and AMED in addition to a review of
      unpublished material. All included papers were critically appraised using a
      modified PEDro critical appraisal tool. Thirty-three studies were eligible,
      assessing the outcomes of 3532 TKRs. Analysis suggested that there was no
      significant difference in clinical or radiological outcomes and complication
      rates between fixed- and mobile-bearing TKRs.

PMID- 19851757
TI  - Sertindole improves sub-chronic PCP-induced reversal learning and episodic memory
      deficits in rodents: involvement of 5-HT(6) and 5-HT (2A) receptor mechanisms.
AB  - AIM: This study examined the efficacy of sertindole in comparison with a
      selective 5-HT(6) and a 5-HT(2A) receptor antagonist to reverse sub-chronic
      phencyclidine (PCP)-induced cognitive deficits in female rats. METHODS: In the
      first test, adult female hooded Lister rats were trained to perform an operant
      reversal learning task to 90% criterion. After training, rats were treated with
      PCP at 2 mg/kg (i.p.) or vehicle twice daily for 7 days, followed by 7 days
      washout. For the second test, novel object recognition (NOR), a separate batch of
      rats, had the same sub-chronic PCP dosing regime and washout period. In reversal
      learning, rats were treated acutely with sertindole, the selective 5-HT(2A)
      receptor antagonist M100.907 or the selective 5-HT(6) receptor antagonist SB
      742457. RESULTS: The PCP-induced selective reversal learning deficit was
      significantly improved by sertindole, M100.907 and SB-742457. Sertindole also
      significantly improved the sub-chronic PCP-induced deficit in NOR, a test of
      episodic memory following a 1 min and 1 h inter-trial interval. In vivo binding
      studies showed that the dose-response relationship for sertindole in this study
      most closely correlates with affinity for 5-HT(6) receptor in vivo binding in
      striatum, although contribution from binding to 5-HT(2A) receptors in vivo in
      cortex may also provide an important mechanism. CONCLUSION: The efficacies of
      selective 5-HT(2A) and 5-HT(6) receptor antagonists suggest potential mechanisms
      mediating the effects of sertindole, which has high affinity for these 5-HT
      receptor subtypes. The sertindole-induced improvement in cognitive function in
      this animal model suggests relevance for the management of cognitive deficit
      symptoms in schizophrenia.

PMID- 19851758
TI  - Gating of vibrotactile detection during visually guided bimanual reaches.
AB  - It is far more difficult to detect a small tactile stimulation on a finger that
      is moving compared to when it is static. This suppression of tactile information
      during motion, known as tactile gating, has been examined in some detail during
      single-joint movements. However, the existence and time course of this gating has
      yet to be examined during visually guided multi-joint reaches, where sensory
      feedback may be paramount. The current study demonstrated that neurologically
      intact humans are unable to detect a small vibratory stimulus on one of their
      index fingers during a bimanual reach toward visual targets. By parametrically
      altering the delay between the visual target onset and the vibration, it was
      demonstrated that this gating was even apparent before participants started
      moving. A follow up experiment using electromyography indicated that gating was
      likely to occur even before muscle activity had taken place. This unique
      demonstration of tactile gating during a task reliant on visual feedback supports
      the notion this phenomenon is due to a central command, rather than a masking of
      sensory signals by afferent processing during movement.

PMID- 19851759
TI  - Influence of accuracy constraints on bimanual coordination during a goal-directed
      task in children with hemiplegic cerebral palsy.
AB  - Previously we found that children with hemiplegic cerebral palsy (CP) have
      impaired bimanual coordination compared to typically developing children during a
      functional drawer-opening task. However, performance of the task under time
      constraints (fast-as-possible) facilitated better bimanual coordination for these
      children. Accuracy is another important task constraint that could influence the
      coordination of the two hands during such tasks. The effect of accuracy
      constraints on bimanual coordination in children with hemiplegic CP is not well
      understood. In the present study, children were asked to reach forward and open a
      drawer with one hand and then activate a light switch inside the drawer with the
      contralateral hand. Task accuracy constraints (different handles and switch
      sizes) were manipulated in order to determine their effect on upper extremity
      coordination. Eleven children with hemiplegic CP (age 8-16 years) and eleven age
      matched typically developing children participated in this study. The results
      show that higher accuracy constraints prolong the total movement completion time
      for both groups of children. However, children with hemiplegic CP demonstrated
      less sequential movement with a higher accuracy constraint (a smaller knob
      handle) than a lower accuracy constraint (a larger loop handle). Nevertheless,
      presentation of both higher accuracy constraints (handle and switch) at the same
      time was detrimental to their performance. These influences of task constraints
      were similar regardless of which hand was used to open the drawer. The results
      suggest that performance may not be linearly related to the constraints, and in
      some cases "more is not better".

PMID- 19851760
TI  - Adaptation to motor-visual and motor-auditory temporal lags transfer across
      modalities.
AB  - Previous research has shown that the timing of a sensor-motor event is
      recalibrated after a brief exposure to a delayed feedback of a voluntary action
      (Stetson et al. 2006). Here, we examined whether it is the sensory or motor event
      that is shifted in time. We compared lag adaption for action-feedback in visuo
      motor pairs and audio-motor pairs using an adaptation-test paradigm. Participants
      were exposed to a constant lag (50 or 150 ms) between their voluntary action
      (finger tap) and its sensory feedback (flash or tone pip) during an adaptation
      period (approximately 3 min). Immediately after that, they performed a temporal
      order judgment (TOJ) task about the tap-feedback test stimulus pairings. The
      modality of the feedback stimulus was either the same as the adapted one (within
      modal) or different (cross-modal). The results showed that the point of
      subjective simultaneity (PSS) was uniformly shifted in the direction of the
      exposed lag within and across modalities (motor-visual, motor-auditory). This
      suggests that the TRE of sensor-motor events is mainly caused by a shift in the
      motor component.

PMID- 19851761
TI  - The effects of multisensory targets on saccadic trajectory deviations:
      eliminating age differences.
AB  - The present study had two aims. First, to determine if bimodal audio-visual
      targets allow for greater inhibition of visual distractors, which in turn may
      lead to greater saccadic trajectory deviations away from those distractors.
      Second, to determine if bimodal targets can reduce age differences in the ability
      to generate deviations away, as older adults tend to benefit more from
      multisensory integration than younger adults. The results show that bimodal
      targets produced larger deviations away than unimodal targets, but only when the
      distractor preceded the target, and this effect was comparable across age groups.
      Furthermore, in contrast to previous research, older adults in this study showed
      similar deviations away from distractors to those of younger adults. These
      findings suggest that age differences in the production of trajectory deviations
      away are not inevitable and that multisensory integration may be an important
      means for increasing top-down inhibition of irrelevant distraction.

PMID- 19851762
TI  - Manual obstacle avoidance takes into account visual uncertainty, motor noise, and
      biomechanical costs.
AB  - Moving around obstacles requires balancing the need to avoid collisions with the
      need to minimize biomechanical costs. We investigated this tradeoff by studying
      the effects of visual uncertainty, motor noise, and practice on clearance over
      obstacles in a manual positioning task. Participants moved a manipulandum back
      and forth over a stationary obstacle. We varied visual uncertainty by placing the
      obstacle at different heights relative to participants' eyes, and we varied motor
      noise by having participants hold the object to be moved at different positions
      relative to the range of motion of the arm joints. Clearance was larger in
      conditions of higher visual uncertainty than in conditions of lower visual
      uncertainty, larger in the higher motor noise conditions than in the lower motor
      noise conditions, and larger early in practice than late in practice. The results
      indicate that spatial accuracy and biomechanical costs are both taken into
      account during reaching over obstacles, but to differing degrees across practice.

PMID- 19851763
TI  - Adaptive and phase transition behavior in performance of discrete multi-articular
      actions by degenerate neurobiological systems.
AB  - The identification of attractors is one of the key tasks in studies of
      neurobiological coordination from a dynamical systems perspective, with a
      considerable body of literature resulting from this task. However, with regards
      to typical movement models investigated, the overwhelming majority of actions
      studied previously belong to the class of continuous, rhythmical movements. In
      contrast, very few studies have investigated coordination of discrete movements,
      particularly multi-articular discrete movements. In the present study, we
      investigated phase transition behavior in a basketball throwing task where
      participants were instructed to shoot at the basket from different distances.
      Adopting the ubiquitous scaling paradigm, throwing distance was manipulated as a
      candidate control parameter. Using a cluster analysis approach, clear phase
      transitions between different movement patterns were observed in performance of
      only two of eight participants. The remaining participants used a single movement
      pattern and varied it according to throwing distance, thereby exhibiting
      hysteresis effects. Results suggested that, in movement models involving many
      biomechanical degrees of freedom in degenerate systems, greater movement
      variation across individuals is available for exploitation. This observation
      stands in contrast to movement variation typically observed in studies using more
      constrained bi-manual movement models. This degenerate system behavior provides
      new insights and poses fresh challenges to the dynamical systems theoretical
      approach, requiring further research beyond conventional movement models.

PMID- 19851765
TI  - [Report on the Pedopathology Working Group].

PMID- 19851764
TI  - Identification and characterisation of a novel immune-type receptor (NITR) gene
      cluster in the European sea bass, Dicentrarchus labrax, reveals recurrent gene
      expansion and diversification by positive selection.
AB  - In the last decade, a new gene family encoding non-rearranging receptors, called
      novel immune-type receptors (NITRs), has been discovered in teleost fish. NITRs
      belong to the immunoglobulin superfamily and represent an extraordinarily
      divergent and rapidly evolving gene complex. Genomic analysis of a region
      spanning 270 kb led to the discovery of a NITR gene cluster in the European sea
      bass (Dicentrarchus labrax). In total, 27 NITR genes and three putative
      pseudogenes, organised in a tandemly arrayed cluster, were identified. Sea bass
      NITR genes maintain the three major genomic organisations that appear to be
      essentially conserved among fish species along with new features presumably
      involving processes of intron loss, exon deletion and acquisition of new exons.
      Comparative and evolutionary analyses suggest that these receptors have evolved
      following a "birth-and-death" model of gene evolution in which duplication events
      together with lineage-specific gain and loss of individual members contributed to
      the rapid diversification of individual gene families. In this study, we
      demonstrate that species-specific gene expansions provide the raw material for
      diversifying, positive Darwinian selection favouring the evolution of a highly
      diverse array of molecules.

PMID- 19851766
TI  - Consensus report of the 2nd International Forum for Liver MRI.
AB  - Discussion at the 2nd Forum for Liver MRI: The International Primovist User
      Meeting on the use of the hepatocyte-specific contrast agent gadolinium
      ethoxybenzyl-diethylene triamine penta-acetic acid (Gd-EOB-DTPA) is reported.
      Changes to the currently recommended Gd-EOB-DTPA imaging protocol were identified
      that can reduce the overall examination time. The potential benefits of 3-T MR
      imaging using Gd-EOB-DTPA have yet to be fully explored. Data show that Gd-EOB
      DTPA-enhanced MRI allows identification of liver lesions and provides a
      differential diagnosis of hepatocellular nodules in the noncirrhotic and
      cirrhotic liver, based on vascularity, during the dynamic arterial, portal-venous
      and late phases, and during the hepatocytespecific phase. Current European,
      American and Japanese guidelines for the diagnosis of hepatocellular carcinoma
      need to take into account the recent rapid advances in liver imaging. Based on
      published clinical trials and the experience of the attendees in the use of Gd
      EOB-DTPA in liver imaging, a new simplified, non-invasive diagnostic algorithm
      was proposed that would be applicable to both Eastern and Western clinical
      practice in the evaluation of hepatocarcinogenesis and hepatocellular carcinoma.
      Preliminary clinical experience suggests that Gd-EOB-DTPA may also provide an
      innovative and cost-effective one-stop approach for staging rectal cancer using
      wholebody imaging.

PMID- 19851767
TI  - Acute acalculous cholecystitis in systemic sclerosis.

PMID- 19851768
TI  - Valvular heart disease in systemic lupus erythematosus and Jaccoud's arthropathy.
AB  - Jaccoud's arthropathy (JA) was initially described as a secondary complication to
      rheumatic fever (RF). However, most recently described cases are associated with
      systemic lupus erythematosus (SLE). At least in RF, this articular complication
      has been observed to occur in association with valvular heart disease. The aim of
      this work is to investigate the presence of valvulopathy in patients with SLE and
      JA, when compared to lupus patients without such complication. Patients with
      diagnosis of SLE based on the American College of Rheumatology criteria were
      enrolled in the study and divided into two groups: with or without JA and
      evaluated by transthoracic echocardiography. A total of 113 patients with SLE (25
      with JA and 88 without JA) were assessed, of which 108 were females and five were
      males. Echocardiographic changes were found in 24 patients (21.2%) out of the
      entire population, including valvulopathy in 17 cases (15%), pulmonary
      hypertension in 7 cases (6.2%) and pericardial effusion in 2 cases (1.8%). In
      general, echocardiographic changes were more frequently seen in the JA group in
      comparison with the control group (p = 0.04). Additionally, in the JA group,
      valvulopathy was found in nine cases (36%) against eight cases (9%) in the
      control group (p = 0.001). This study reveals for the first time the association
      between the presence of valvular heart disease and JA in SLE patients, suggesting
      that the presence of JA may be a marker of such complication. Additional studies
      are required for clarification of the mechanisms involved in both complications.

PMID- 19851769
TI  - Systemic lupus erythematosus as a first presentation of common variable
      immunodeficiency associated with infrequent mannose-binding lectin gene
      polymorphisms.
AB  - The association of common variable immunodeficiency (CVID) and systemic lupus
      erythematosus (SLE) is infrequent. Mannose-binding lectin (MBL) has been shown to
      play a role in CVID and SLE. The purpose of this study is to describe two cases
      of CVID who presented as SLE and also evaluate the presence of MBL polymorphisms
      and MBL serum levels in those patients. In both patients, SLE was the first
      manifestation of CVID. In these patients the SLE immunological markers and
      disease activity disappeared after the development of CVID. They carried the very
      infrequent MBL haplotype 4Q-57Glu. One of them had a homozygous genotype, whereas
      the other patient was heterozygous and also presented the haplotype 4P-57Glu that
      had never been previously detected. Interestingly, this last patient was
      presenting frequent respiratory tract infections, developed bronchiectasis and
      had low levels of circulating MBL. These results may support the role of MBL in
      the development of autoimmunity in CVID. Further genetic studies are needed to
      clarify the role of the MBL polymorphisms in the development of autoimmunity in
      CVID.

PMID- 19851770
TI  - Anaplastic large cell lymphoma in a patient with rheumatoid arthritis.
AB  - It is known that patients with rheumatoid arthritis (RA) have an increased risk
      for non-Hodgkin's lymphomas in comparison with the general population. Although
      increased risk of lymphoma is attributed to the disease activity, the drugs used
      in the therapy of RA may also cause increased risk of malignancy. Herein, we
      report on an RA patient who developed non-Hodgkin's lymphoma after methotrexate
      therapy and review the literature about it. A 74-year-old man with RA had been
      treated with low-dose methotrexate and subsequently developed anaplastic large
      cell lymphoma of the T-cell phenotype. Anaplastic large cell lymphoma has been
      reported rarely in rheumatoid arthritis.

PMID- 19851771
TI  - Ultrasonographic assessment of clinically diagnosed trigger fingers.
AB  - This study examines flexor digitorum tendons and A1 pulley in patients presenting
      trigger fingers using high-resolution ultrasonography (US), determines the
      accurate causes of trigger fingers, and analyzes the relationship between
      clinical data and US findings. As much as 50 trigger fingers of 41 patients were
      examined by high-resolution US, and the US findings were analyzed as tendon
      thickness, fibrillar echotexture, tendon margin, fluid collection, A1 pulley
      thickening, tendon sheath cyst, and metacarpophalageal (MCP) joint abnormalities.
      The affected fingers were compared with the asymptomatic opposite sides. Right
      thumb and ring finger were the most common fingers involved. Mean thickness of
      flexor digitorum tendons of the affected fingers was increased significantly,
      compared with that of the opposite fingers. There were various US findings in
      flexor digitorum tendons as follows; loss of normal fibrillar echogenic pattern
      (14%), irregularity or blurring of the tendon margin (62%), and fluid collection
      in the tendon sheath (16%). Thickening of A1 pulley was noted in 44% of fingers,
      and mean thickness of A1 pulley was 0.7 mm. As much as 6% of fingers had the
      sheath cysts and 4% of fingers had abnormalities of MCP joints. The patients with
      extension difficulty of the fingers had thicker flexor digitorum tendon than
      those without. The patients with locking fingers had more blurred margin of the
      tendon than those without. US can detect various lesions in clinical trigger
      fingers, and some US findings correlated with clinical findings.

PMID- 19851772
TI  - A 2-year comparative open label randomized study of efficacy and safety of
      etanercept and infliximab in patients with ankylosing spondylitis.
AB  - The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to
      nonsteroidal antiinflammatory drugs, corticosteroids, and disease modifying
      antirheumatic drugs in quite a number of patients. Tumor necrosis factor
      inhibitors have demonstrated to be of value in reducing AS disease activity in
      clinical trials. The efficacy and safety of both etanercept and infliximab in
      patients with ankylosing spondylitis were compared in a 2-year open label
      randomised study. Our results are consistent with a significant more rapid
      clinical improvement in the infliximab treated group. Treatment with both
      etanercept and infliximab at the end of the study was effective, safe, and well
      tolerated.

PMID- 19851773
TI  - Infliximab therapy in pediatric Takayasu's arteritis: report of two cases.
AB  - Takayasu arteritis (TA) is a chronic vasculitis of unknown etiology. Experience
      with anti-tumor necrosis factor alpha (anti-TNF) agents in difficult-to-treat
      patients with TA is limited and refers to adult patients. Here, we present two
      cases of pediatric TA treated with infliximab, in which clinical remission was
      observed. Anti-TNF treatment represents a useful therapy in pediatric Takayasu
      arteritis too, especially to avoid the risk of long-term corticosteroids
      toxicity.

PMID- 19851774
TI  - Monitoring gene expression of potato under salinity using cDNA microarrays.
AB  - The molecular response to salt exposure was studied in the leaves of a Solanum
      tuberosum clone using cDNA microarray. Differentially expressed genes were
      classified according to their known or predicted function and their expression
      ratio as compared to the control. The major changes upon a 150 mM NaCl exposure
      in potato leaves occurred in the photosystem apparatus and Calvin cycle: many
      transcripts coding for proteins belonging to photosystems I and II and
      chlorophyll synthesis were repressed. On the other hand, we observed the
      induction of various kinds of transcription factors implicated in osmotic stress
      response via ABA-dependent or ABA-independent pathways but also in plant defense
      pathways. This revealed a crosstalk between abiotic and biotic stress responses
      during salt exposure, which activated several adaptation mechanisms including
      heat shock proteins, late embryogenesis abundant, dehydrins and PR proteins. Gene
      expression changes related to carbohydrate and amino acid metabolism were also
      observed, pointing at putative modifications at the metabolic level.

PMID- 19851776
TI  - Deletion of 15q11.2-15q13.1 in isolated human hemimegalencephaly.

PMID- 19851775
TI  - Upregulation of endothelin receptors A and B in the nitrofen induced hypoplastic
      lung occurs early in gestation.
AB  - PURPOSE: Pulmonary hypoplasia and persistent pulmonary hypertension (PPH)
      aggravate clinical courses in congenital diaphragmatic hernia (CDH). Endothelin 1
      enhances PPH by vasoconstriction and proliferation of vessel walls. Up-regulation
      of pulmonary Endothelin Receptors A and B (EDNRA, EDNRB) has been reported in
      human CDH and animal models, but the onset of those alterations during lung
      development remains unclear. We hypothesized that pulmonary expression of EDNRA
      and EDNRB is up-regulated at early gestational stages in the nitrofen model.
      METHODS: Pregnant rats were exposed to nitrofen or vehicle on gestational day 9
      (D9). Embryos were sacrificed on D15, D18 and D21 and divided into nitrofen- and
      control group. Pulmonary RNA was extracted and mRNA levels of EDNRA and EDNRB
      were determined by real-time PCR. Immunohistochemistry for protein expression of
      both receptors was performed. RESULTS: mRNA levels of EDNRA and EDNRB were
      significantly increased in the nitrofen group on D15, D18 and D21.
      Immunohistochemistry revealed increased pulmonary vascular expression of EDNRA
      and EDNRB compared to controls. CONCLUSION: Altered expression of EDNRA and EDNRB
      is an early event in lung morphogenesis in the nitrofen model. We speculate that
      pulmonary arteries in CDH become excessively muscularised in early fetal life,
      becoming unable to adapt normally at birth.

PMID- 19851777
TI  - Capparis spinosa protects against oxidative stress in systemic sclerosis dermal
      fibroblasts.
AB  - High reactive oxygen species (ROS), Ha-Ras, and active ERK1/2 in fibroblasts play
      an essential role in the pathogenesis of systemic sclerosis (SSc). The present
      study was carried out to evaluate the effects of the ethanol extract from fruits
      of Capparis Spinosa L. (ECS) on oxidative stress and ROS-ERK1/2-Ha-Ras signal
      loop in SSc dermal fibroblasts in vitro. Cultured dermal fibroblasts from three
      SSc patients and three normal controls were treated with ECS by different
      concentration (10, 50, 100 microg/ml). ECS significantly reduced the production
      of O2(-), H2O2, and ROS in SSc fibroblasts in a dose-dependent manner. ECS
      effectively minimized the loss of cell viability and apoptosis induced by H2O2 in
      normal and SSc fibroblasts. Furthermore, the protective effect of ECS on SSc
      fibroblasts was more significant than on normal ones. ECS decreased the
      expression of P-ERK1/2 and Ha-Ras in a dose-dependent manner. In conclusion, ECS
      exhibits a notable activity in protecting against oxidative stress and
      interrupting of ROS-ERK1/2-Ha-Ras signal loop in SSc, suggesting its potential
      protective effects against skin sclerosis.

PMID- 19851778
TI  - The maxillary sinus after total laryngectomy: an electron microscopic study.
AB  - Nasal breathing is completely ceased after total laryngectomy. This results in
      some structural changes in the nasal mucosa, which has been described in numerous
      studies. This study investigates the changes that appear in the paranasal sinus
      mucosa. Eight patients who had undergone total laryngectomy at least 1-year ago
      were enrolled. Under general anesthesia, maxillary sinuses were examined with an
      endoscope inserted through canine fossa. 1-2 mm mucosal tissues for biopsy were
      taken from posterior wall of the maxillary sinus. Specimens were evaluated under
      an electron microscope. Control tissues for biopsy were obtained from two
      patients who had been operated for other reasons and analyzed under transmission
      electron microscopy. Results showed that in the control specimens, the epithelial
      cells appeared normal under transmission electron microscopy. Samples taken from
      two larygectomees in their first postoperative year were also completely normal.
      Samples from other larygectomees demonstrated ciliary loss, abundant degenerative
      vacuoles in ciliated epithelial cells and detachments in the interepithelial
      junctional complexes. The intracellular respiratory mechanisms such as the
      mitochondria, golgi complex and endoplasmic reticulum cisternae, and the
      integrity of the cellular or the nuclear membrane were spared. We conclude that
      the cessation of nasal breathing resulted in degenerative changes that could be
      reversible in the transmission electron microscopic examination of maxillary
      sinus mucosa. These changes emerged after 2 years following total laryngectomy.
      Nevertheless, these changes did not have any negative influence on the clinical
      outcome in this group of patients.

PMID- 19851779
TI  - The shape of caveolae is omega-like after glutaraldehyde fixation and cup-like
      after cryofixation.
AB  - Caveolae were defined as flask- or omega-shaped plasma membrane invaginations,
      abundant in adipocytes, fibroblasts, endothelial and smooth muscle cells. The
      major protein component of caveolar membranes is an integral membrane protein
      named caveolin. We compared the freeze-fracture behavior of caveolae in
      glutaraldehyde-fixed and cryofixed mouse fibroblast cells and found distinct
      differences. In glutaraldehyde-fixed cells almost all caveolae were cross
      fractured through their pore and only very few caveolar membranes were membrane
      fractured. We found the reverse situation in rapid frozen cells without any
      chemical fixation where most of the caveolae were membrane-fractured, showing
      different degrees of invagination from nearly flat to deeply invaginated. In
      ultrathin sections of glutaraldehyde-fixed heart endothelial cells, caveolae
      exhibit the well known omega-like shape. In high-pressure frozen, freeze
      substituted and low temperature embedded heart endothelial cells, the caveolae
      frequently exhibit a cup-like shape without any constriction or pore. The cup
      like caveolar shape could also be shown by tilt series analysis of freeze
      fracture replicas obtained from cryofixed cells. Freeze-fracture immunolabeling
      of caveolin-1 revealed a lateral belt-like caveolin alignment. These findings
      point out that the constricted "neck" region of caveolae in most cases is an
      effect that is caused and intensified by the glutaraldehyde fixation. Our data
      indicate that caveolae in vivo show all degrees of invagination from nearly flat
      via cup-like depressed to in a few cases omega-like.

PMID- 19851780
TI  - Hyperbaric oxygenation alleviates MCAO-induced brain injury and reduces hydroxyl
      radical formation and glutamate release.
AB  - The present study examined the effect of hyperbaric oxygen (HBO) on the formation
      of 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA),
      the products of salicylate trapping of hydroxyl free radicals, and glutamate
      release in the striatum during acute ischemia and reperfusion. Non-HBO rats (n =
      8) were subjected to 1-h ischemia. Study rats (n = 8) were treated with HBO at
      2.8 ATA for 1 h during ischemia. Artificial CSF solution containing 5 mM sodium
      salicylate was perfused at 1 microl/min. Samples were continuously collected at
      15 min intervals and the levels of 2,3-DHBA, 2,5-DHBA, and glutamate were
      analyzed. The lesion volume was determined by TTC stain. Occlusion of the middle
      cerebral artery induced a significant increase in the levels of 2,3-DHBA and 2,5
      DHBA. A peak of approximately two and fourfold of baseline levels was reached at
      45 min and was maintained at elevated levels during reperfusion. The level of
      glutamate increased approximately two times at 30 min during ischemia, continued
      to increase, and reached approximately three times baseline level during
      reperfusion. HBO significantly alleviated brain injury associated with decreased
      levels of 2,3-DHBA, 2,5-DHBA and glutamate. This study suggests that the
      decreased glutamate release and the reduced formation of hydroxyl free radicals
      might contribute to the neuroprotective effect of HBO.

PMID- 19851781
TI  - Gender-specific ischemic tissue tolerance in critically perfused skin.
AB  - PURPOSE: The purpose of this study is to determine gender-specific differences in
      the development of necrosis in persistent ischemic tissue and to analyze whether
      differences are due to gender-specific loss of vascular reactivity or change in
      ischemic tolerance. METHODS: Hairless mice (skh-1) of both genders were assigned
      to three groups of adolescent, adult, and senescent age. Critical ischemia was
      induced by transection of the two distal pedicles of the animal's ear.
      Microcirculation was assessed over a 5-day period using intravital
      epifluorescence microscopy. Tissue necrosis, blood flow, functional capillary
      density (FCD), red blood cell (RBC) velocity, and capillary diameter were
      analyzed. RESULTS: Induction of persistent ischemia caused an age-dependent
      demarcation of nonperfused flap tissue. Adult and senescent females developed
      markedly more necrosis than age-matched males (49 +/-1% vs. 37 +/-3% and 53 +/-
      3% vs. 44 +/- 2%, respectively; p<0.05), whereas no gender-specific difference in
      flap necrosis was observed in adolescent animals (31 +/- 2% vs. 33 +/- 3%).
      Gender did not affect the amount of microcirculatory dysfunction in the flap.
      Thus, age-matched females and males exhibited a comparable decrease of FCD, RBC
      velocity, and capillary dilatory response. CONCLUSIONS: Both age and female
      gender may predispose for an increased susceptibility to develop ischemic tissue
      necrosis. The increased necrosis in female animals does not apply to an
      aggravated microvascular dysfunction, but rather to a reduced ischemic tissue
      tolerance.

PMID- 19851782
TI  - Possible hidden hazards of mass vaccination against new influenza A/H1N1: have
      the cardiovascular risks been adequately weighed?
AB  - Programs for vaccination against the new influenza A/H1N1 targeting many hundred
      million citizens in Europe and the USA are to be launched in the fall of this
      year. The USA is planning to employ a non-adjuvanted vaccine, whereas European
      nations are opting for inclusion of MF59, the adjuvant contained in an
      alternative seasonal flu vaccine, or the related adjuvant AS03 that is contained
      in a recently developed H5N1 vaccine. We draw attention to unappreciated hazards
      of using adjuvanted vaccine in Europe. Evidence from animal experiments in
      conjunction with clinical epidemiological data indicates that, quite irrespective
      of cause, stimulation of the immune system may accelerate atherogenesis.
      Application of adjuvanted flu vaccines to individuals at risk may therefore
      aggravate the course of underlying atherosclerotic vessel disease with all the
      clinical consequences. The same may hold true for other widespread diseases that
      are propelled by deregulated immune mechanisms. Safety trials conducted to date
      have not specifically taken these possible side effects into account, and
      unexpected serious adverse effects thus may follow in the wake of a general
      vaccination program. A prudent consequence would be to establish careful survey
      systems alongside with mass application of new adjuvanted vaccines, or to hold
      mass vaccination in reserve for use only in situations of true need, such as
      would arise with the emergence of a more virulent new H1N1 virus strain, or to
      use non-adjuvanted vaccines in individuals who are potentially at risk for
      adverse side effects.

PMID- 19851783
TI  - The in vitro effect of mefloquine and praziquantel against juvenile and adult
      Schistosoma japonicum.
AB  - Mefloquine, an antimalarial drug, has been found to be effective against various
      stages of schistosomes in vivo. The purpose of the study is to explore the in
      vitro effect of mefloquine against adult and juvenile Schistosoma japonicum and
      to compare its efficacy with praziquantel. Three-hour-old schistosomula were
      prepared by penetrating the mouse skin with schistosome cercariae, while
      schistosomes 7-, 14-, and 35-day-old were collected from mice infected with S.
      japonicum cercariae for 7, 14, and 35 days by perfusion. Schistosomes were placed
      to each of 24 wells of a Falcon plate and maintained in Hanks' balanced salt
      solution-20% calf serum. Besides observation on the direct in vitro effect of
      mefloquine and praziquantel, adult worms exposed to mefloquine and praziquantel
      for 1 and 4 h were transferred to the medium without the drugs and incubated
      continuously for another 72 h. The reversible effect of mefloquine and
      praziquantel was assessed by the recovery of the worm motor activity and parasite
      survival. The minimal effective concentration of mefloquine against adult
      schistosomes in vitro was 10 microg/mL, which revealed that the worm motor
      activity was first stimulated, then decreased significantly, followed by bleb
      formation, focal swelling and elongation of the worm body, cessation of gut
      peristalsis, and death of 56.3% (18/32) worms within 24-72 h. Similar appearance
      was seen in the adult worms exposed to higher mefloquine concentration of 20 and
      30 microg/mL, but all worms died within 4-24 h. The adult schistosomes exposed to
      praziquantel 1-30 microg/mL showed fast spasmodic contraction of the worm body,
      followed by bleb formation along the tegument, feeble movement of oral sucker,
      and death of a part of males and females 72 h after incubation. When male and
      female schistosomes exposed to mefloquine 10 and 20 microg/mL for 1 and 4 h were
      transferred to the medium without the drug, no apparent recovery of worm motor
      activity and survival was seen. In case of worms exposed to praziquantel at the
      same concentration for 1 and 4 h before replacement of drug-free medium, a well
      recovery of worm motor activity, looseness of worm body, and reduction or
      disappearance of blebs along the tegument were observed. Mefloquine also
      exhibited in vitro effect against 3-h-old and 7- and 14-day-old schistosomula
      which was similar to that seen in adult worms, but all or parts of worms showed
      decrease in motor activity or even death (3-h-old and 7-day-old schistosomula) at
      a lower mefloquine concentration of 5 microg/mL. In 14 day-old schistosomula
      exposed to praziquantel 1-30 microg/mL, spasmodic contraction and significant
      decrease in motor activity of the worm body with movement of oral and ventral
      suckers were observed, but no death of worm was seen during a 3-day incubation
      period. The results indicate that in vitro mefloquine exhibits a direct killing
      effect against adult and juvenile S. japonicum which is different from that of
      praziquantel. Meanwhile, the juvenile schistosomes are more susceptible to
      mefloquine than the adult ones. Furthermore, the in vitro effect of mefloquine
      against adult schistosomes is irreversible, while that of praziquantel is
      reversible.

PMID- 19851784
TI  - The unfolded protein response and its relevance to connective tissue diseases.
AB  - The unfolded protein response (UPR) has evolved to counter the stresses that
      occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This
      sophisticated quality control system attempts to restore homeostasis through the
      action of a number of different pathways that are coordinated in the first
      instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged
      ER-stress-related UPR can have detrimental effects on cell function and, in the
      longer term, may induce apoptosis. Connective tissue cells such as fibroblasts,
      osteoblasts and chondrocytes synthesise and secrete large quantities of proteins
      and mutations in many of these gene products give rise to heritable disorders of
      connective tissues. Until recently, these mutant gene products were thought to
      exert their effect through the assembly of a defective extracellular matrix that
      ultimately disrupted tissue structure and function. However, it is now becoming
      clear that ER stress and UPR, because of the expression of a mutant gene product,
      is not only a feature of, but may be a key mediator in the initiation and
      progression of a whole range of different connective tissue diseases. This review
      focuses on ER stress and the UPR that characterises an increasing number of
      connective tissue diseases and highlights novel therapeutic opportunities that
      may arise.

PMID- 19851786
TI  - Beta-glucosidase coating on polymer nanofibers for improved  cellulosic ethanol
      production.
AB  - Beta-glucosidase (betaG) can relieve the product inhibition of cellobiose in the
      cellulosic ethanol production by converting cellobiose into glucose. For the
      potential recycled uses, betaG was immobilized and stabilized in the form of
      enzyme coating on polymer nanofibers. The betaG coating (EC-betaG) was fabricated
      by crosslinking additional betaG molecules onto covalently attached betaG
      molecules (CA-betaG) via glutaraldehyde treatment. The initial activity of EC
      betaG was 36 times higher than that of CA-betaG. After 20 days of incubation
      under shaking, CA-betaG and EC-betaG retained 33 and 91% of each initial
      activity, respectively. Magnetic nanofibers were also used for easy recovery and
      recycled uses of betaG coating. It is anticipated that the recycled uses of
      highly active and stable betaG coating can improve the economics of cellulosic
      ethanol production so long as economical materials are employed as a host of
      enzyme immobilization.

PMID- 19851787
TI  - Influence of season on plasma antidiuretic hormone, angiotensin II, aldosterone
      and plasma renin activity in young volunteers.
AB  - We investigated seasonal changes in hormonal and thermoregulatory responses.
      Eight volunteers were subjected to the experiment at four times of the year:
      around the vernal and autumnal equinoxes, and at the summer and winter solstices
      at latitude 35 degrees N. Plasma antidiuretic hormone (ADH), angiotensin II (ANG
      II), aldosterone (ALD) and plasma renin activity (PRA) were analyzed before and
      after water immersion. Seasonal changes in thermoregulatory responses were
      assessed by measuring core temperature and sweat rate during immersion of the leg
      in hot water (at 42 degrees C) for 30 min in a room maintained at 26 degrees C.
      The concentration of plasma ADH and ALD before water immersion was significantly
      higher in summer than in other seasons. The concentrations of ANG II and PRA did
      not show seasonal variations. Changes in tympanic temperature during water
      immersion showed significant differences between seasons, and were higher in
      winter than in other seasons. The sweat rate was significantly higher in summer
      than in other seasons. In summary, ADH and ALD concentrations displayed a
      seasonal rhythm with marked elevation in summer; this may be a compensative
      mechanism to prevent dehydration from increased sweat loss during summer due to
      heat acclimatization.

PMID- 19851788
TI  - Grapevine bud break prediction for cool winter climates.
AB  - Statistical analysis of bud break data for grapevine (Vitis vinifera L. cvs.
      Riesling and Muller-Thurgau) at 13 sites along the northern boundary of
      commercial grapevine production in Europe revealed that, for all investigated
      sites, the heat summation method for bud break prediction can be improved if the
      starting date for the accumulation of heat units is specifically determined.
      Using the coefficient of variance as a criterion, a global minimum for each site
      can be identified, marking the optimum starting date. Furthermore, it was shown
      that the application of a threshold temperature for the heat summation method
      does not lead to an improved prediction of bud break. Using site-specific
      parameters, bud break of grapevine can be predicted with an accuracy of +/- 2.5
      days. Using average parameters, the prediction accuracy is reduced to +/- 4.5
      days, highlighting the sensitivity of the heat summation method to the quality
      and the representativeness of the driving temperature data.

PMID- 19851789
TI  - Passenger thermal perceptions, thermal comfort requirements, and adaptations in
      short- and long-haul vehicles.
AB  - While thermal comfort in mass transportation vehicles is relevant to service
      quality and energy consumption, benchmarks for such comfort that reflect the
      thermal adaptations of passengers are currently lacking. This study reports a
      field experiment involving simultaneous physical measurements and a questionnaire
      survey, collecting data from 2,129 respondents, that evaluated thermal comfort in
      short- and long-haul buses and trains. Experimental results indicate that high
      air temperature, strong solar radiation, and low air movement explain why
      passengers feel thermally uncomfortable. The overall insulation of clothing worn
      by passengers and thermal adaptive behaviour in vehicles differ from those in
      their living and working spaces. Passengers in short-haul vehicles habitually
      adjust the air outlets to increase thermal comfort, while passengers in long-haul
      vehicles prefer to draw the drapes to reduce discomfort from extended exposure to
      solar radiation. The neutral temperatures for short- and long-haul vehicles are
      26.2 degrees C and 27.4 degrees C, while the comfort zones are 22.4-28.9 degrees
      C and 22.4-30.1 degrees C, respectively. The results of this study provide a
      valuable reference for practitioners involved in determining the adequate control
      and management of in-vehicle thermal environments, as well as facilitating design
      of buses and trains, ultimately contributing to efforts to achieve a balance
      between the thermal comfort satisfaction of passengers and energy conserving
      measures for air-conditioning in mass transportation vehicles.

PMID- 19851790
TI  - Clarifying springtime temperature reconstructions of the medieval period by gap
      filling the cherry blossom phenological data series at Kyoto, Japan.
AB  - We investigated documents and diaries from the ninth to the fourteenth centuries
      to supplement the phenological data series of the flowering of Japanese cherry
      (Prunus jamasakura) in Kyoto, Japan, to improve and fill gaps in temperature
      estimates based on previously reported phenological data. We then reconstructed a
      nearly continuous series of March mean temperatures based on 224 years of cherry
      flowering data, including 51 years of previously unused data, to clarify
      springtime climate changes. We also attempted to estimate cherry full-flowering
      dates from phenological records of other deciduous species, adding further data
      for 6 years in the tenth and eleventh centuries by using the flowering phenology
      of Japanese wisteria (Wisteria floribunda). The reconstructed tenth century March
      mean temperatures were around 7 degrees C, indicating warmer conditions than at
      present. Temperatures then fell until the 1180s, recovered gradually until the
      1310s, and then declined again in the mid-fourteenth century.

PMID- 19851791
TI  - Self-reported assessment of disability and performance-based assessment of
      disability are influenced by different patient characteristics in acute low back
      pain.
AB  - For an individual, the functional consequences of an episode of low back pain is
      a key measure of their clinical status. Self-reported disability measures are
      commonly used to capture this component of the back pain experience. In non-acute
      low back pain there is some uncertainty of the validity of this approach. It
      appears that self-reported assessment of disability and direct measurements of
      functional status are only moderately related. In this cross-sectional study, we
      investigated this relationship in a sample of 94 acute low back pain patients.
      Both self-reported disability and a performance-based assessment of disability
      were assessed, along with extensive profiling of patient characteristics. Scale
      consistency of the performance-based assessment was investigated using Cronbach's
      alpha, the relationship between self-reported and performance-based assessment of
      disability was investigated using Pearson's correlation. The relationship between
      clinical profile and each of the disability measures were examined using
      Pearson's correlations and multivariate linear regression. Our results
      demonstrate that the battery of tests used are internally reliable (Cronbach's
      alpha = 0.86). We found only moderate correlations between the two disability
      measures (r = 0.471, p < 0.001). Self-reported disability was significantly
      correlated with symptom distribution, medication use, physical well-being, pain
      intensity, depression, somatic distress and anxiety. The only significant
      correlations with the performance-based measure were symptom distribution,
      physical well-being and pain intensity. In the multivariate analyses no
      psychological measure made a significant unique contribution to the prediction of
      the performance-based measure, whereas depression made a unique contribution to
      the prediction of the self-reported measure. Our results suggest that self
      reported and performance-based assessments of disability are influenced by
      different patient characteristics. In particular, it appears self-reported
      measures of disability are more influenced by the patient's psychological status
      than performance-based measures of disability.

PMID- 19851792
TI  - Expert's comment concerning Grand Rounds case entitled "Langerhans cell
      histiocytosis of the atlas in an adult" (by Wo Quan Zhong, Liang Jiang, Qing Jun
      Ma, Zhong Jun Liu, Xiao Guang Liu, Feng Wei, Hui Shu Yuan, Geng Ting Dang).

PMID- 19851793
TI  - Classification of thoracolumbar fractures and dislocations.
AB  - A classification of injuries is necessary in order to develop a common language
      for treatment indications and outcomes. Several classification systems have been
      proposed, the most frequently used is the Denis classification. The problem of
      this classification system is that it is based on an assumption, which is
      anatomically unidentifiable: the so-called middle column. For this reason, few
      years ago, a group of spine surgeons has developed a new classification system,
      which is based on the severity of the injury. The severity is defined by the
      pathomorphological findings, the prognosis in terms of healing and potential of
      neurological damage. This classification is based on three major groups: A =
      isolated anterior column injuries by axial compression, B = disruption of the
      posterior ligament complex by distraction posteriorly, and group C =
      corresponding to group B but with rotation. There is an increasing severity from
      A to C, and within each group, the severity usually increases within the
      subgroups from .1, .2, .3. All these pathomorphologies are supported by a
      mechanism of injury, which is responsible for the extent of the injury. The type
      of injury with its groups and subgroups is able to suggest the treatment
      modality.

PMID- 19851795
TI  - Hydrogen bonding interactions in PN...HX complexes: DFT and ab initio studies of
      structure, properties and topology.
AB  - Spin-restricted DFT (X3LYP and B3LYP) and ab initio (MP2(fc) and CCSD(fc))
      calculations in conjunction with the Aug-CC-pVDZ and Aug-CC-pVTZ basis sets were
      performed on a series of hydrogen bonded complexes PN...HX (X = F, Cl, Br) to
      examine the variations of their equilibrium gas phase structures, energetic
      stabilities, electronic properties, and vibrational characteristics in their
      electronic ground states. In all cases the complexes were predicted to be stable
      with respect to the constituent monomers. The interaction energy (Delta E)
      calculated using a super-molecular model is found to be in this order: PN...HF >
      PN...HCl > PN...HBr in the series examined. Analysis of various physically
      meaningful contributions arising from the Kitaura-Morokuma (KM) and reduced
      variational space self-consistent-field (RVS-SCF) energy decomposition procedures
      shows that the electrostatic energy has significant contribution to the over-all
      interaction energy. Dipole moment enhancement (Delta mu) was observed in these
      complexes expected of predominant dipole-dipole electrostatic interaction and was
      found to follow the trend PN...HF > PN...HCl > PN...HBr at the CCSD level.
      However, the DFT (X3LYP and B3LYP) and MP2 levels less accurately determined
      these values (in this order HF < HCl < HBr). Examination of the harmonic
      vibrational modes reveals that the PN and HX bands exhibit characteristic blue-
      and red shifts with concomitant bond contraction and elongation, respectively, on
      hydrogen bond formation. The topological or critical point (CP) analysis using
      the static quantum theory of atoms in molecules (QTAIM) of Bader was considered
      to classify and to gain further insight into the nature of interaction existing
      in the monomers PN and HX, and between them on H-bond formation. It is found from
      the analysis of the electron density rho ( c ), the Laplacian of electron charge
      density nabla(2)rho(c), and the total energy density (H ( c )) at the critical
      points between the interatomic regions that the interaction N...H is indeed
      electrostatic in origin (rho(c) > 0, nabla(2)rho(c) > 0 and H(c) > 0 at the BCP)
      whilst the bonds in PN (rho(c) > 0, nabla(2)rho(c) > 0 and H(c) < 0) and HX
      ((rho(c) > 0, nabla(2)rho(c) < 0 and H(c) < 0)) are predominantly covalent. A
      natural bond orbital (NBO) analysis of the second order perturbation energy
      lowering, E((2)), caused by charge transfer mechanism shows that the interaction
      N...H is n(N) --> BD*(HX) delocalization.

PMID- 19851794
TI  - Structural organization of human Cu-transporting ATPases: learning from building
      blocks.
AB  - Copper-transporting ATPases (Cu-ATPases) ATP7A and ATP7B play an essential role
      in human physiological function. Their primary function is to deliver copper to
      the secretory pathway and export excess copper from the cell for removal or
      further utilization. Cells employ Cu-ATPases in numerous physiological processes
      that include the biosynthesis of copper-dependent enzymes, lactation, and
      response to hypoxia. Biochemical studies of human Cu-ATPases and their orthologs
      have demonstrated that Cu-ATPases share many common structural and mechanistic
      characteristics with other members of the P-type ATPase family. Nevertheless, the
      Cu-ATPases have a unique coordinate environment for their ligands, copper and
      ATP, and additional domains that are required for sophisticated regulation of
      their intracellular localization and activity. Here, we review recent progress
      that has been made in understanding the structure of Cu-ATPases from the analysis
      of their individual domains and orthologs from microorganisms, and speculate
      about the implications of these findings for the function and regulation of human
      copper pumps.

PMID- 19851796
TI  - Control of flowering time and spike development in cereals: the earliness per se
      Eps-1 region in wheat, rice, and Brachypodium.
AB  - The earliness per se gene Eps-A ( m ) 1 from diploid wheat Triticum monococcum
      affects heading time, spike development, and spikelet number. In this study, the
      Eps1 orthologous regions from rice, Aegilops tauschii, and Brachypodium
      distachyon were compared as part of current efforts to clone this gene. A single
      Brachypodium BAC clone spanned the Eps-A ( m ) 1 region, but a gap was detected
      in the A. tauschii physical map. Sequencing of the Brachypodium and A. tauschii
      BAC clones revealed three genes shared by the three species, which showed higher
      identity between wheat and Brachypodium than between them and rice. However, most
      of the structural changes were detected in the wheat lineage. These included an
      inversion encompassing the wg241-VatpC region and the presence of six unique
      genes. In contrast, only one unique gene (and one pseudogene) was found in
      Brachypodium and none in rice. Three genes were present in both Brachypodium and
      wheat but were absent in rice. Two of these genes, Mot1 and FtsH4, were
      completely linked to the earliness per se phenotype in the T. monococcum high
      density genetic map and are candidates for Eps-A ( m ) 1. Both genes were
      expressed in apices and developing spikes, as expected for Eps-A ( m ) 1
      candidates. The predicted MOT1 protein showed amino acid differences between the
      parental T. monococcum lines, but its effect is difficult to predict. Future
      steps to clone the Eps-A ( m ) 1 gene include the generation of mot1 and ftsh4
      mutants and the completion of the T. monococcum physical map to test for the
      presence of additional candidate genes.

PMID- 19851798
TI  - Conjugated linoleic acid isomers, t10c12 and c9t11, are differentially
      incorporated into adipose tissue and skeletal muscle in humans.
AB  - Conjugated linoleic acid (CLA) is a popular supplement believed to enhance immune
      function, body composition and insulin sensitivity, but results of scientific
      studies investigating its effects are conflicting. The isomer- and tissue
      specific effects of CLA may explain these conflicting results. Therefore, this
      study quantified the incorporation of the c9t11 and t10c12 CLA isomers into
      adipose tissue and skeletal muscle in response to supplementation in healthy,
      regularly-exercising, non-obese persons. The CLA group (n = 14) ingested 3.9 g
      per day CLA (50:50 t9c11:c10t12) and the placebo group (n = 11) 3.9 g per day
      high-oleic-acid sunflower oil for 12 weeks. Following supplementation, the t10c12
      isomer was incorporated into adipose tissue triacylglycerol (P < 0.001), and the
      c9t11 isomer tended to increase in skeletal muscle phospholipids (P = 0.056).
      Therefore, human adipose tissue and skeletal muscle are enriched with CLA in an
      isomer-specific manner.

PMID- 19851797
TI  - Glutamatergic and GABAergic effects of fipronil on olfactory learning and memory
      in the honeybee.
AB  - We investigated here the role of transmissions mediated by GABA and glutamate
      gated chloride channels (GluCls) in olfactory learning and memory in honeybees,
      both of these channels being a target for fipronil. To do so, we combined
      olfactory conditioning with injections of either the GABA- and glutamate
      interfering fipronil alone, or in combination with the blocker of glutamate
      transporter L-trans-Pyrrolidine-2,4-Dicarboxylicacid (L-trans-PDC), or the GABA
      analog Trans-4-Aminocrotonic Acid (TACA). Our results show that a low dose of
      fipronil (0.1 ng/bee) impaired olfactory memory, while a higher dose (0.5 ng/bee)
      had no effect. The detrimental effect induced by the low dose of fipronil was
      rescued by the coinjection of L-trans-PDC but was rather increased by the
      coinjection of TACA. Moreover, using whole-cell patch-clamp recordings, we
      observed that L-trans-PDC reduced glutamate-induced chloride currents in antennal
      lobe cells. We interpret these results as reflecting the involvement of both
      GluCl and GABA receptors in the impairment of olfactory memory induced by
      fipronil.

PMID- 19851799
TI  - Determination of lipid degradation by marine lipase-producing bacteria: critical
      evaluation of lipase activity assays.
AB  - With the aim of obtaining a better understanding of lipids-lipases interactions
      in bacterioplankton communities in oceans, we used different methods for
      measuring lipase activities in pure cultures of the marine strain Alteromonas
      macleodii. The decay of tripalmitate added to cultures was followed chemically
      over time. In an enzymatic approach, lipase activities were measured using the
      fluorogenic lipid analogs MUF-palmitate and ELF-palmitate. When hydrolyzed by
      lipase, the non-fluorescent substrates release MUF and ELF Alcohol (ELFA) which
      are fluorescent. As shown by spectrofluorometry, ELF-palmitate was an efficient
      competitor for MUF-palmitate. However, the activities reached using these two
      fluorogenic substrates were different, but still much higher than the
      tripalmitate hydrolysis rate, measured chemically. MUF- and ELF-palmitate would
      not be hydrolyzed by lipase sensu stricto (defined as triacylglycerol
      acylesterase E.C. 3.1.1.3) but rather reflects lipolytic activities in a broad
      sense. ELFA is also water-insoluble and theoretically precipitates in the
      external membrane of bacteria causing its hydrolysis, which would allow
      microscopic identification of active cells. By epifluorescence microscopy, the
      accumulation of ELFA fluorescence over time was detected (as large, diffuse
      halos), but no precipitates were clearly associated with bacteria on slide
      preparations, neither for pure cultures of Alteromonas macleodii nor for natural
      samples from the Bay of Marseille, France. Among possible biases, those related
      to the hydrophobic/hydrophilic conditions required for precipitation are
      discussed.

PMID- 19851800
TI  - Contrast medium induced nephropathy in patients undergoing percutaneous coronary
      intervention for acute coronary syndrome: differences in STEMI and NSTEMI.
AB  - The aim of this study was to assess the incidence, clinical predictors, and
      outcome of patients developing contrast medium induced nephropathy (CIN) after
      percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).
      BACKGROUND: CIN is associated with significant higher morbidity and mortality
      after coronary intervention. Recently it was shown, that patients undergoing
      percutaneous coronary intervention for acute myocardial infarction have a
      significant higher risk of developing CIN. Non-ST-elevating myocardial infarction
      (NSTEMI) patients (pts) might be at an even higher risk developing CIN than
      patients with ST-elevating myocardial infarction (STEMI), because of presenting
      older and more often with diabetes. METHODS: In 392 consecutive ACS patients
      developing myocardial infarction and therefore undergoing emergent coronary
      angiography between October 2004 and March 2007, we measured serum creatinine
      concentration (Cr) at baseline and each day of the following 3 days. Contrast
      medium induced nephropathy was defined as an increase in Cr > 0.5 mg/dl. ACS was
      defined according to the guidelines of the German Society of Cardiology. RESULTS:
      Overall, 392 pts were included: 203 (51.8%) with STEMI and 189 (48.2%) with
      NSTEMI. Patients with STEMI developed more often a cardiogenic shock (18 vs. 6%;
      P < 0.001) whereas patients with NSTEMI were older (67 vs. 61 years; P < 0.001)
      and presenting with a higher co-morbidity. Forty-five (11.5%) pts developed CIN;
      22 (10.8%) in the STEMI group and 23(12.2%) in the NSTEMI group (P = 0.75).
      Patients developing CIN presented a more complicated clinical course and a
      significantly longer hospital stay (14 vs. 10 days; P < 0.001). The mortality
      rate was also significantly higher (16 vs. 6%; P < 0.05). CONCLUSION: This
      prospective study showed no differences in the incidence of developing CIN in
      patients undergoing PCI for STEMI or NSTEMI, but the predisposing factors,
      however, differed significantly. Although STEMI patients needed significantly
      more contrast medium for revascularisation, they did not develop CIN more often.
      CIN was associated with higher in-hospital complication rate and mortality. Thus,
      better preventive strategies according to the different predisposing factors
      leading to CIN are needed to reduce morbidity and mortality, especially in high
      risk patients.

PMID- 19851802
TI  - Dietary intake and plasma concentrations of PUFA and LC-PUFA in breastfed and
      formula fed infants under real-life conditions.
AB  - BACKGROUND: The breastfed infant is usually used as standard for formula feeding,
      also regarding long-chain polyunsaturated fatty acids (LC-PUFA). Here, plasma
      fatty acid concentrations in formula fed infants and the effects of LC-PUFA
      supplementation were investigated under real-life conditions. METHOD: Term
      healthy infants being fully milk fed until the age of 4 months were categorized
      as breast milk "BM" (n = 73) if consuming >95% of energy from breast milk or
      formula (F) if consuming >95% of energy from formula subdivided into formula
      without (F-) (n = 15) and with LC-PUFA supplementation (F+) (n = 15). Formula as
      marketed was chosen by the parents. Dietary fatty acids (FA) intake was
      calculated from continuous dietary records from 2 months of age onwards. Total
      plasma FA were analyzed at the age of 4 months with docosahexaenoic acid (DHA) as
      primary outcome. RESULTS: Dietary ratios of the polyunsaturated fatty acids
      (PUFA; linoleic acid/alpha-linolenic acid) were smaller in both F groups than in
      the BM group. Plasma DHA as % of total FA was similar in BM and F(+) but higher
      in BM in absolute amounts (mg/L). Plasma DHA as % of total FA in F(-) was higher
      than what might be supposed on the basis of dietary intake. CONCLUSION: Infants
      consuming present-day LC-PUFA-supplemented formula achieved plasma LC-PUFA
      concentrations similar to breastfed infants. In infants consuming non-LC-PUFA
      supplemented formula, the favorable PUFA pattern of the formula may have
      supported n-3 LC-PUFA biosynthesis.

PMID- 19851801
TI  - Prevention of oxidative DNA damage in inner organs and lymphocytes of rats by
      green tea extract.
AB  - BACKGROUND: Consumption of green tea (GT) is associated with decreased incidences
      of specific forms of cancer in humans and it was postulated that its antioxidant
      (AO) properties may account for these effects. The evidence for AO effects of GT
      is mainly based on the results from in vitro experiments and on animal studies in
      which protection against chemically induced damage was monitored. AIM OF THE
      STUDY: The goal of the study was the investigation of the prevention of strand
      breaks and DNA migration attributable to endogenous oxidation of bases by GT
      extract (GTE) in inner organs and lymphocytes of untreated rats. In addition,
      immunological parameters and biochemical markers were monitored. METHODS: DNA
      migration was measured in hepatocytes, colonocytes and lymphocytes after
      consumption of a low (1.3 mg/kg bw per day, 5 days) and a high dose (6.5 mg/kg bw
      per day, 5 days) of GTE in COMET assays (n = 5 animals per group). In addition,
      immunological parameters (TNF-alpha, IFN-gamma, IL-4 and IL-10), the total AO
      capacity and oxidized low-density lipoproteins were determined in plasma.
      RESULTS: No evidence for reduction in DNA damage was found with a lower dose,
      whereas with the higher dose, reduction in DNA migration attributable to
      formamidopyrimidine-DNA-glycosylase sensitive lesions (oxidized purines) and
      endonuclease III-sensitive sites (oxidized pyrimidines) (58 and 73%) was observed
      in lymphocytes; also, in colonocytes (reduction in FPG-sensitive sites by 46%)
      and hepatocytes (decrease in Endo III-sensitive sites by 74%) protective effects
      were found, while none of the other parameters was altered. CONCLUSIONS: Our
      results show that a dose of GTE, which is equivalent to consumption of 500 ml
      GT/p/day in humans protects lymphocytes and to a lesser extent inner organs
      against oxidative DNA damage, while no effect was seen with a lower dose
      corresponding to an uptake of 100 ml/p/day.

PMID- 19851805
TI  - Methanol as the primary methanogenic and acetogenic precursor in the cold Zoige
      wetland at Tibetan plateau.
AB  - Previous studies suggested that methanol and acetate were the likely methanogenic
      precursors in the cold Zoige wetland. In this study, the contribution of the two
      substances to methanogenesis and the conversion in Zoige wetland were analyzed.
      It was determined that methanol supported the highest CH(4) formation rate in the
      enrichments of the soil grown with Eleocharis valleculosa, and even higher at 15
      degrees C than at 30 degrees C; while hydrogenotrophic methanogenesis was higher
      at 30 degrees C. Both methanol- and acetate-using methanogens were counted at the
      highest (10(7) g(-1)) in the soil, whereas methanol-using acetogens (10(8) g(-1))
      were ten times more abundant than either methanol- or acetate-using methanogens.
      Both methanol and acetate were detected in the methanogenesis-inhibited soil
      samples, so that both could be the primary methanogenic precursors in E.
      valleculosa soil. However, the levels of methanol and acetate accumulated in 2
      bromoethane-sulfonate (BES)- and CHCl(3)-treated soils were in reverse, i.e.,
      higher methanol in CHCl(3)- and higher acetate in BES-treated soil, so that
      methanol-derived methanogenesis could be underestimated due to the consumption by
      acetogens. Analysis of the soil 16S rRNA genes revealed Acetobacterum bakii and
      Trichococcus pasteurii to be the dominant methanol-using acetogens in the soil,
      and a strain of T. pasteurii was isolated, which showed the high conversion of
      methanol to acetate at 15 degrees C.

PMID- 19851803
TI  - Extrastriatal dopamine D(2) receptor occupancy in olanzapine-treated patients
      with schizophrenia.
AB  - Olanzapine is described as a multi-acting receptor-targeted antipsychotic agent.
      Although regional differences of dopamine D(2) receptor occupancy, i.e., limbic
      selectivity, were reported for olanzapine, contradictory results were also
      reported. We measured dopamine D(2) receptor occupancy of olanzapine in
      extrastriatal regions in patients with schizophrenia using positron-emission
      tomography with [(11)C]FLB457 and the plasma concentrations of olanzapine. Ten
      patients with schizophrenia taking 5-20 mg/day of olanzapine participated.
      Dopamine D(2) receptor occupancy in the temporal cortex ranged from 61.1 to
      85.8%, and plasma concentration was from 12.7 to 115.4 ng/ml. The ED(50) value
      was 3.4 mg/day for dose and 10.5 ng/ml for plasma concentration. The ED(50)
      values obtained in this study were quite similar to those previously reported in
      the striatum. In conclusion, although the subjects and methods were different
      from previous striatal occupancy studies, these results suggest that limbic
      occupancy by olanzapine may not be so different from that in the striatum.

PMID- 19851806
TI  - Ten years of Swedish experience with intraductal electrohydraulic lithotripsy and
      laser lithotripsy for the treatment of difficult bile duct stones: an effective
      and safe option for octogenarians.
AB  - BACKGROUND: Endoscopic procedures using electrohydraulic lithotripsy (EHL) or
      intraductal laser lithotripsy (ILL) are the methods of choice for managing
      difficult common bile duct (CBD) stones. This retrospective study examined 10
      years of Swedish experience using a mother-baby endoscopic system to assist in
      the fragmentation of CBD stones by EHL and ILL. METHODS: Between 1995 and 2006,
      44 patients with a median age of 80 years underwent EHL or ILL at two Swedish
      centers after conventional endoscopic fragmentation of CBD stones had failed.
      Long-term follow-up assessment was conducted for 9 to 126 months (median, 53
      months). RESULTS: Final stone clearance after EHL or ILL treatment with or
      without additional conventional endoscopic retrograde cholangiopancreatography
      (ERCP) was achieved for 34 (77%) of 44 patients. The results for 10 patients
      (23%) were defined as failures. Complete or partial stone fragmentation and
      definitive duct clearance were achieved in one session for 23 patients (52%). A
      second EHL or ILL attempt made in five cases of primary failure led to definitive
      stone clearance in three cases. Two patients experienced perioperative
      complications (stone basket impaction). Mild post-ERCP pancreatitis occurred for
      one patient and cholangitis for two patients. During long-term follow-up
      evaluation, recurrent CBD stones were found in one patient. CONCLUSIONS: Peroral
      endoscopic EHL or ILL, under direct cholangioscopic visualization by a mother
      baby endoscopic system, is an effective treatment for difficult CBD stones. The
      technique can be used safely even in frail and elderly patients. However, several
      endoscopic attempts may be required before final stone clearance is achieved. The
      vast majority of patients may be expected to remain symptom free for a prolonged
      period.

PMID- 19851807
TI  - Short-term outcomes of laparoscopic total mesorectal excision following
      neoadjuvant chemoradiotherapy.
AB  - OBJECTIVE: To investigate the feasibility of laparoscopic total mesorectal
      excision (TME) in mid and lower rectal cancers following neoadjuvant
      chemoradiation (nCRT). BACKGROUND: The laparoscopic approach for colon cancer has
      been widely accepted. A few studies have shown that there are advantages of
      laparoscopic over open TME surgery for rectal cancer. However, the role of
      laparoscopy has not been clearly defined specifically in cases following nCRT.
      METHODS: All patients with rectal cancer who underwent nCRT were identified; no
      operations for rectal carcinoma were performed laparoscopically between 1997 and
      2005. The laparoscopic cases were matched to open cases based on gender,
      procedure, age, and body mass index (BMI). The medical records were reviewed and
      short-term outcome was compared between these two groups. Statistical analysis
      was performed using SPSS 15 software. RESULTS: Between 2002 and 2008, 64 patients
      were identified, including 32 patients who underwent laparoscopic surgery and 32
      who had a laparotomy. There was no difference between the two groups based on
      gender, procedure, age, BMI or American Society of Anesthesiologists (ASA)
      classification. The procedures performed within each group included 8
      abdominoperineal resections and 24 anterior resections, which included 20 colonic
      J-pouch-anal anastomoses and 4 straight coloanal anastomoses. In the laparoscopic
      group, 12 patients underwent totally laparoscopic operations, 12 were either
      laparoscopic-assisted or hand-assisted procedures, and 8 were converted to
      laparotomy. The reasons for conversion included bleeding, splenic injury, and
      difficult anatomy. There were no differences in comorbidities, tumor location,
      tumor size, tumor stage or radiation dose between the two groups. Operative time
      was longer in the laparoscopic group (267 + or - 76 versus 205 + or - 49 min, p <
      0.001). Operative blood loss, complication rate, and mortality rate were all
      similar between the two groups. However, the laparoscopic group benefited from
      shorter length of stay (6.1 + or - 2.4 versus 7.6 + or - 2.3 days, p = 0.012),
      earlier first bowel movement (1.9 + or - 1 versus 3.3 + or - 2.4 days, p =
      0.006), and shorter time to regular diet (3.9 + or - 2.1 versus 5.8 + or - 2.5
      days, p = 0.003). There was no difference in lymph node harvest (both positive
      node harvest and total lymph node harvest), distal margin or radial margin.
      CONCLUSIONS: In our experience, laparoscopic TME for mid and lower rectal cancer
      is feasible and safe. Patients benefit from the short-term advantages of
      laparoscopy, including shorter length of hospital stay, time to tolerating a
      regular diet, and time to first bowel movement or stoma function. Although there
      were no short-term differences in oncologic parameters, the long-term oncologic
      outcome requires further investigation.

PMID- 19851808
TI  - Impact of selection bias on the utilization of adjuvant therapy for pancreas
      adenocarcinoma.
AB  - BACKGROUND: Improved outcomes have been associated with the use of adjuvant
      therapy after resection of pancreas adenocarcinoma. However, the frequency with
      which patients receive adjuvant therapy and the factors impacting its use remain
      largely undefined. We hypothesized that nonutilization of adjuvant therapy was
      primarily associated with patient comorbidity and onset of postoperative
      complications. METHODS: A prospectively maintained database was reviewed to
      identify patients who underwent potentially curative resection of histologically
      confirmed pancreas adenocarcinoma at our institution from January 1996 to May
      2007. Clinicopathological data and postoperative treatment history were collected
      to identify variables associated with receipt of adjuvant therapy. RESULTS: Of
      119 patients, 33% did not receive adjuvant therapy. The frequency with which
      patients underwent adjuvant therapy did not change over time. On multivariate
      analysis, patient age 70 years or greater, major postoperative complications,
      distal pancreatectomy, absence of nodal metastases, and absence of perineural
      invasion were associated with decreased utilization of adjuvant therapy.
      DISCUSSION: One-third of patients in this contemporary dataset of patients did
      not go on to receive adjuvant therapy. The likelihood of receiving adjuvant
      treatment is negatively impacted by the course of postoperative recovery.
      Moreover, the fact that adjuvant therapy was undertaken less often for older
      patients and patients with favorable pathological features highlights the
      selection bias impacting the decision to pursue postoperative therapy for this
      disease. This selective utilization of postoperative therapy for patients with
      adverse oncological characteristics is likely to bias any retrospective analysis
      attempting to measure the efficacy of adjuvant treatment for pancreas
      adenocarcinoma.

PMID- 19851809
TI  - Surgery for esophageal cancer: quality of life matters.

PMID- 19851810
TI  - Minimesohepatectomy for colorectal liver metastasis invading the middle hepatic
      vein at the hepatocaval confluence.
AB  - BACKGROUND: In case of liver tumors invading the middle hepatic vein (MHV) at the
      hepatocaval confluence (HC) major resection is recommended. We describe a new
      ultrasound-guided conservative operation for patients with colorectal liver
      metastasis (CLM) invading the MHV at the HC. METHODS: The case of a 65-year-old
      woman with two CLMs is described. One CLM was in segments 4-superior (S4
      superior) and 8-ventral (S8-ventral) with invasion of the MHV 2 cm from the HC,
      while the other was in segment 8-dorsal (cranial portion). J-shaped laparotomy
      and intraoperative ultrasonography (IOUS) were carried out. Anterior surface of
      the HC was exposed, and compression using the surgeon's fingertips was applied at
      the MHV. Once reversal flow in the peripheral portion of the MHV, and/or shunting
      collaterals with right or left hepatic vein, and/or hepatopetal flow in portal
      branches to right paramedian section (P5-8) and/or to segment 4-inferior (P4
      inferior) were detected by color Doppler IOUS (CD-IOUS), partial resection of S4
      superior and S8-ventral with vascular resection of MHV was performed. RESULTS:
      The disclosure of those three criteria by CD-IOUS enables the performance of
      minimesohepatectomy. No congestion of the remnant liver was found. Ninety-day
      mortality and morbidity were nil. The patient was discharged 8 days after
      surgery. At 11 months of follow-up the patient underwent percutaneous
      radiofrequency ablation for a new 15-mm CLM in segment-8-dorsal (caudal portion).
      Currently, the patient is alive and free of disease at 17 months after surgery.
      CONCLUSIONS: The use of CD-IOUS may allow conservative resection of liver tumors
      invading the MHV at the HC. This might limit the need for larger resections, and
      broadens the role of IOUS in optimizing surgical strategy.

PMID- 19851811
TI  - Recurrence of adrenal cortical carcinoma following resection: surgery alone can
      achieve results equal to surgery plus mitotane.
AB  - BACKGROUND: A recent nonrandomized interinstitutional study reported that
      adjuvant mitotane following surgery for adrenocortical carcinoma (ACC) was
      associated with decreased recurrence. Because of the limitations of this study,
      we investigated the influences of surgery and adjuvant mitotane in a large series
      of ACC patients evaluated and treated at a single referral center. STUDY DESIGN:
      Retrospective evaluation of patients followed at a single institution after
      surgery for ACC. RESULTS: 218 patients with ACC underwent primary resection
      either at the index institution [surgery index (SI), n = 28] or an outside
      institution [surgery outside (SO), n = 190] and had a median follow-up of 88
      months. SI patients had a superior disease-free survival compared with SO
      patients (median 25 versus 12 months, P = 0.003), and SI patients also had a
      superior overall survival compared with SO patients (median not reached versus 44
      months, P = 0.02). Factors predicting increased risk of recurrence on
      multivariate analysis were surgery at an outside institution [hazard ratio (HR)
      2.56, 95% confidence interval (CI) 1.44-4.53, P = 0.001] and no treatment with
      adjuvant mitotane (HR 1.95, 95% CI 1.06-3.59, P = 0.03), and those predicting a
      poorer survival were advanced stage at presentation (P = 0.01) and surgery at an
      outside institution (HR 2.62, 95% CI 1.31-5.25, P = 0.007). CONCLUSIONS: The
      recurrence rate of the index group (50%) in the current series, the overwhelming
      majority of whom did not receive adjuvant mitotane, is indistinguishable from
      that reported for those who received adjuvant mitotane (49%) in the recent
      interinstitutional report, emphasizing the importance of completeness of initial
      surgery in the management of patients with ACC.

PMID- 19851812
TI  - General model of inflammation.
AB  - Dysfunctions in the immune system, due to genetics, disease or environmental
      factors, can cause bacterial colonization and chronic inflammation. In cystic
      fibrosis and chronic obstructive pulmonary disease, respiratory infections can
      initiate inflammation of the airway. We propose a system of nonlinear ordinary
      differential equations to describe interactions between macrophages, both
      inflammatory and anti-inflammatory cytokines, and bacteria. Small changes in
      parameters governing inflammatory cytokine production and macrophage sensitivity
      to cytokines result in dramatically different model behaviors. When the immune
      system is functioning properly, a non-aggressive pathogen will not provide a
      sufficient trigger to initiate chronic inflammation, however, in disease positive
      feedback of the inflammatory cytokine can induce chronic inflammation even after
      a bacterial infection has been resolved. In addition, if the macrophage
      population is more sensitive to inflammatory cytokines small perturbations
      initiated by bacteria will also lead to chronic inflammation. We have found
      nonaggressive bacteria are able to initiate chronic inflammation and propose why
      anti-inflammatory cytokine therapy may not be effective in resolving this
      inflammation.

PMID- 19851814
TI  - Low-intensity ultrasound increases FAK, ERK-1/2, and IRS-1 expression of intact
      rat bones in a noncumulative manner.
AB  - BACKGROUND: Low-intensity pulsed ultrasound stimulation (LIPUS) reportedly
      increases osteogenesis in fracture models but fails in intact bone, suggesting
      LIPUS does not act on mechanotransduction and growth factor pathways of intact
      bone. QUESTIONS/PURPOSES: We asked whether daily 20-minute LIPUS applied to
      intact tibias would act on bone proteins involved in mechanotransduction (focal
      adhesion kinase [FAK], and extracellular signal-regulated kinase-1/2 [ERK-1/2]),
      and growth factor signaling (insulin receptor substrate-1 [IRS-1]) pathways at 7,
      14, and 21 days of treatment. METHODS: Immunoblotting was performed to detect
      FAK, ERK-1/2, and IRS-1 expression and activation from the stimulated intact
      tibias at 7, 14, and 21 days of daily 20-minute LIPUS. RESULTS: LIPUS increased
      FAK expression (at 7 days), ERK-1/2 (at 14 days), and IRS-1 (at 7 days), but
      expression decreased 7 days later, indicating a noncumulative effect of LIPUS. As
      only FAK expression was detected at 21 days, these observations suggest LIPUS
      influences nuclear reactions that may be modulated by a major cellular mechanism
      preferentially inhibiting IRS-1 expression and not FAK expression. Increased ERK
      1/2 expression at 14 days suggests the differing mechanisms for promoting ERK
      1/2, FAK, and IRS-1 syntheses. IRS-1 expression behaved similarly to FAK
      expression; therefore, LIPUS may modulate growth factor pathways. LIPUS increased
      sustained FAK and ERK-1/2 activation, but not IRS-1, suggesting sustained ERK-1/2
      activation is not the result of mechanically induced growth factor activation.
      CONCLUSIONS: LIPUS acts on mechanotransduction and growth factor pathways in
      intact bone in a noncumulative manner. Clinical relevance These data suggest
      LIPUS applied to intact bone acts on proteins involved in osteogenesis.

PMID- 19851816
TI  - Iliopsoas bursa injections can be beneficial for pain after total hip
      arthroplasty.
AB  - Impingement of the iliopsoas tendon is an uncommon cause of groin pain after
      total hip arthroplasty (THA). We asked whether selective steroid and anesthetic
      injections for iliopsoas tendonitis after THA would relieve pain and improve
      function. We retrospectively reviewed 27 patients with presumed iliopsoas
      tendinitis treated by fluoroscopically guided injections of the iliopsoas bursa.
      Pre- and immediately postinjection, questionnaires and telephone followup
      questionnaires were administered to determine patient outcomes. Four patients
      were lost to followup and we were unable to obtain information from relatives on
      an additional four; the questionnaire was administered to the remaining 19
      patients, including six who subsequently had surgery at an average of 44.6 months
      (range, 25-68 months) after their first injection. The average modified Harris
      hip score in the 19 patients improved from 61 preinjection to 82 postinjection
      and the average pain improved from 6.4 preinjection to 2.9 postinjection, but
      eight patients (30%) required a second injection at an average of 8.2 months
      after the first injection. Ultimately, six patients (22%) had an additional
      surgical procedure to address the underlying cause of the iliopsoas irritation.
      Iliopsoas tendonitis is uncommon after THA but should be considered in the
      differential diagnosis of all patients who present with groin pain after THA.
      Selective steroid and anesthetic injections of the iliopsoas bursa give adequate
      pain relief in the majority of patients and should be considered part of the
      nonoperative treatment plan before surgical release of the iliopsoas tendon or
      component revision. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 19851815
TI  - Is sclerotherapy better than intralesional excision for treating aneurysmal bone
      cysts?
AB  - BACKGROUND: Minimally invasive approaches such as sclerotherapy have been
      introduced to treat aneurysmal bone cysts. Sclerotherapy has been associated with
      reasonable healing rates during the past two decades. However, it is unclear
      whether sclerotherapy compares with the more traditional extended curettage and
      bone grafting. QUESTIONS/PURPOSES: We therefore compared the healing rates and
      functional scores in patients having percutaneous repetitive sclerotherapy using
      polidocanol (Group 1) with those with intralesional excision (extended curettage
      with a high-speed burr) and bone grafting (Group 2) for treatment of aneurysmal
      bone cyst. PATIENTS AND METHODS: We randomly divided 94 patients into two
      treatment groups. We assessed healing rates (primary outcome measure), pain
      relief, time to healing and recurrence, hospital stay, and the Enneking
      functional score. Forty-five patients from Group 1 and 46 from Group 2 were
      available for study. The minimum followup was 3.2 years (mean, 4.4 years; range,
      3.2-6.1 years). RESULTS: At last followup, 93.3% in Group 1 and 84.8% in Group 2
      had achieved healing. Complications in Group 1 were minor and resolved. In Group
      2, three patients had deep infections and five had superficial infections, and
      two had growth disturbances. Although the healing rates were similar, we found
      higher rates of clinically important complications, worse functional outcomes,
      and higher hospital burden associated with intralesional excision. CONCLUSIONS:
      Repetitive sclerotherapy using polidocanol is a minimally invasive, safer method
      of treatment for aneurysmal bone cysts compared with intralesional excision and
      bone grafting. In this preliminary study, we found similar recurrence rates for
      the two treatment methods, however, this will require confirmation in larger
      studies. LEVEL OF EVIDENCE: Level II, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 19851817
TI  - Results of 32 allograft-prosthesis composite reconstructions of the proximal
      femur.
AB  - The use of allograft-prosthesis composites for reconstruction after bone tumor
      resection at the proximal femur has generated considerable interest since the
      mid1980s on the basis that their use would improve function and survival, and
      restore bone stock. Although functional improvement has been documented, it is
      unknown whether these composites survive long periods and whether they restore
      bone stock. We therefore determined long-term allograft-prosthesis composite
      survival, identified major complications that led to revision, and determined
      whether allograft bone stock could be spared at the time of revision. We also
      compared the radiographic appearance of allografts sterilized by gamma radiation
      and fresh-frozen allografts. We retrospectively reviewed 32 patients with bone
      malignancy in the proximal femur who underwent reconstruction with a cemented
      allograft-prosthesis composite. The allograft-prosthesis composite was a primary
      reconstruction for 23 patients and a revision procedure for nine. The minimum
      followup was 2 months (median, 68 months; range, 2-232 months). The cumulative
      incidence of revision for any reason was 14% at 5 years (95% confidence interval,
      1%-28%) and 19% at 10 years (95% confidence interval, 3%-34%). Nine patients
      (28%) had revision of the reconstruction during followup; four of these patients
      had revision surgery for infection. Allografts sterilized by gamma radiation
      showed worse resorption than fresh-frozen allografts. Based on reported results,
      allograft-composite prostheses do not appear to improve survival compared with
      megaprostheses. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 19851818
TI  - Is MRI adequate to detect lesions in patients with ankle instability?
AB  - BACKGROUND: Chondral lesions, peroneal tendon tears, and other disorders in
      patients with chronic ankle instability may not be detected by preoperative MRI.
      Also, MRI often is obtained and interpreted at the referring institution, leading
      to variability in reading. QUESTIONS/PURPOSES: We assessed the accuracy of the
      radiologists' and orthopaedic surgeon's reading of preoperative MRI for
      diagnosing ankle lesions in patients with ankle instability warranting surgery.
      PATIENTS AND METHODS: We retrospectively reviewed 133 patients who underwent 135
      surgeries for lateral ankle ligament reconstruction with concomitant ankle
      arthroscopy and who had preoperative MRI. RESULTS: We found 72 associated lesions
      in 66 of the 135 surgeries, including 38 chondral injuries, 18 peroneus brevis
      tears, seven loose bodies, and nine other miscellaneous abnormalities.
      Eliminating eight lesions for which the decision to operate was not based on
      operative findings, there were 127 surgeries with 64 associated lesions that
      required intraoperative confirmation or were detected intraoperatively. In the
      original reports, the radiologists identified 39% (15) of the chondral injuries,
      56% (10) of the peroneal tears, and 57% (four) of the loose bodies. Radiologists'
      MRI sensitivity for detecting lesions was 45%. The attending surgeon identified
      47% (18) of the chondral injuries, 89% (16) of the loose bodies, 71% (five) of
      the peroneus brevis tears, and the posterior talus process lesion, with a
      sensitivity of 63%. CONCLUSIONS: Our data suggest orthopaedic surgeons should
      review preoperative MRIs and also suggest the sensitivity of MRI may not be
      adequate to detect lesions in these patients before surgery. LEVEL OF EVIDENCE:
      Level IV, diagnostic study. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 19851819
TI  - Biographical sketch: royal whitman, 1857-1946.
AB  - This biographical sketch of Royal Whitman corresponds to the historic text, The
      Classic: A Study of the Weak Foot, with Reference to its Causes, its Diagnosis,
      and its Cure; with an Analysis of a Thousand Cases of So-Called Flat-Foot,
      available at DOI 10.1007/s11999-009-1130-1 .

PMID- 19851820
TI  - Predictive motor timing performance dissociates between early diseases of the
      cerebellum and Parkinson's disease.
AB  - There is evidence that both the basal ganglia and the cerebellum play a role in
      the neural representation of time in a variety of behaviours, but whether one of
      them is more important is not yet clear. To address this question in the context
      of predictive motor timing, we tested patients with various movement disorders
      implicating these two structures in a motor-timing task. Specifically, we
      investigated four different groups: (1) patients with early Parkinson's disease
      (PD); (2) patients with sporadic spinocerebellar ataxia (SCA); (3) patients with
      familial essential tremor (ET); and (4) matched healthy controls. We used a
      predictive motor-timing task that involved mediated interception of a moving
      target, and we assessed the effect of movement type (acceleration, deceleration
      and constant), speed (slow, medium and fast) and angle (0 degrees , 15 degrees
      and 30 degrees) on performance (hit, early error and late error). The main
      results showed that PD group and arm ET subgroup did not significantly differ
      from the control group. SCA and head ET subjects (severe and mild cerebellar
      damage, respectively) were significantly worse at interception than the other two
      groups. Our findings support the idea that the basal ganglia play a less
      significant role in predictive motor timing than the cerebellum. The fact that
      SCA and ET subjects seemed to have a fundamental problem with predictive motor
      timing suggests that the cerebellum plays an essential role in integrating
      incoming visual information with the motor output in a timely manner, and that ET
      is a heterogeneous entity that deserves increased attention from clinicians.

PMID- 19851822
TI  - Esophageal transit scintigraphy and structured questionnaire in patients with
      systemic sclerosis with endoscopically proven reflux esophagitis.
AB  - OBJECTIVES: Esophageal complications are common in patients with systemic
      sclerosis (SSc). The relationship between gastroesophageal reflux (GER) symptoms
      and dysmotility was examined in endoscopically confirmed patients suspected of
      having reflux esophagitis. METHODS: A total of 32 patients with limited and
      diffuse type SSc (lSSc, dSSc) were examined based on a structured questionnaire
      score (QS) of GER symptoms, retention fraction of esophageal scintigraphy at 90 s
      (R(90)) and gastric emptying time. RESULTS: The QS was significantly higher in
      the reflux esophagitis group than in the non-esophagitis group (5.4 +/- 3.5, 1.4
      +/- 2.9, P = 0.003). When the non-esophagitis group was further divided into lSSc
      and dSSc groups, R(90) was higher in the reflux esophagitis group (31 +/- 18%)
      and the non-esophagitis group with dSSc (34 +/- 32%) than in the non-esophagitis
      group with lSSc (8 +/- 3%, P = 0.02). Both high R(90) >or= 15% and QS >or= 4
      indicated reflux esophagitis. Conversely, both normal R(90) and QS indicated no
      reflux esophagitis. CONCLUSION: A combination of esophageal scintigraphy and
      structured questionnaire demonstrated different aspects of esophageal
      dysfunction, namely dysmotility and GER. Patients with high QS and dysmotility
      may be indicated for further evaluation including endoscopic examination and
      medical treatment.

PMID- 19851821
TI  - Prognostic value of myocardial metabolic imaging with BMIPP in the spectrum of
      coronary artery disease: a systematic review.
AB  - BACKGROUND: We conducted a systematic review to summarize the current literature
      on the prognostic value of BMIPP imaging, fatty-acid metabolic imaging, for the
      prediction of cardiovascular events in coronary artery disease. METHODS AND
      RESULTS: Electronic databases (including Japanese medical literature search
      engines) were searched by a Japanese investigator using a predefined search
      strategy. Eleven studies, all conducted in Japan, were included in the meta
      analysis. In three studies involving 541 patients with suspected acute coronary
      syndrome who were excluded for acute myocardial infarction (AMI), an abnormal
      finding on BMIPP imaging was significantly associated with future hard events
      (cardiac death or non-fatal myocardial infarction). The negative predictive value
      of BMIPP imaging for future hard events was 98.9% (96.8-99.7%) over 3.5 years. In
      six studies involving 542 patients with AMI, a larger defect on BMIPP imaging was
      significantly associated with future hard events. The prognostic value of
      perfusion-metabolism mismatch compared with myocardial perfusion imaging was
      dependent upon the relative timing of BMIPP imaging, revascularization, and
      myocardial perfusion damage. CONCLUSIONS: BMIPP imaging is useful for the risk
      stratification of patients with coronary artery disease, particularly patients
      with acute chest pain.

PMID- 19851823
TI  - Tinnitus in postherpetic neuralgia.
AB  - We describe a woman who developed postherpetic neuralgia (PHN) located on the
      skin areas of the left ophthalmic division of the fifth cranial nerve without
      ocular involvement. PHN was associated with tinnitus, which was located
      ipsilaterally to the painful side and increased in proportion to the intensity of
      pain. Tinnitus was responsive to treatment with duloxetine, 60 mg daily, and
      subsided when the PHN resolved. This is the first description of tinnitus in PHN.

PMID- 19851830
TI  - Effect of adjuvants on immune response and protective immunity elicited by
      recombinant Hsp60 (GroEL) of Salmonella typhi against S. typhi infection.
AB  - Heat shock proteins (Hsps) have been reported to be dominant antigens for the
      host immune response to various pathogens and thus, have great potential for use
      in vaccination. In the present study, we evaluated the immunogenicity and
      protective efficacy of GroEL of Salmonella enterica serovar Typhi against lethal
      infection by S. typhi Ty2 in mice with or without adjuvants. Anti GroEL-IgG
      titers were significantly higher in mice immunized with either GroEL-alone or in
      combination with alum/Complete Freund's adjuvant (CFA) as compared to the
      control. Analysis of antibody isotypes suggested predominance of Th2 type immune
      response in GroEL + alum immunized animals as revealed by higher IgG1/IgG2a
      ratio. Whereas, immunization of animals with GroEL + CFA or GroEL-alone shifted
      the immune response toward Th1 phenotype. Mice immunized with GroEL with or
      without adjuvants, showed a significant increase in lymphocyte proliferation and
      cytokine levels. The animals immunized with GroEL + CFA or GroEL-alone showed
      higher IFN-gamma and IL-2 levels than alum group, indicating Th1 response whereas
      IL-4 levels (Th2 response) were found to be highest in alum group as compared to
      other two immunized groups. Immunization of mice with GroEL-alone, GroEL + alum,
      and GroEL + CFA provided 70, 50 and 80% protection, respectively, against lethal
      challenge by S. typhi in mice. The differences in the percentage protection among
      various groups were attributed to the differences in the immune responses
      generated by respective immunizations. The present study shows that GroEL forms
      an ideal candidate molecule to develop a recombinant protein based vaccine
      against human typhoid.

PMID- 19851829
TI  - Reconciling theories of chaperonin accelerated folding with experimental
      evidence.
AB  - For the last 20 years, a large volume of experimental and theoretical work has
      been undertaken to understand how chaperones like GroEL can assist protein
      folding in the cell. The most accepted explanation appears to be the simplest:
      GroEL, like most other chaperones, helps proteins fold by preventing aggregation.
      However, evidence suggests that, under some conditions, GroEL can play a more
      active role by accelerating protein folding. A large number of models have been
      proposed to explain how this could occur. Focused experiments have been designed
      and carried out using different protein substrates with conclusions that support
      many different mechanisms. In the current article, we attempt to see the forest
      through the trees. We review all suggested mechanisms for chaperonin-mediated
      folding and weigh the plausibility of each in light of what we now know about the
      most stringent, essential, GroEL-dependent protein substrates.

PMID- 19851831
TI  - Adipophilin affects the expression of TNF-alpha, MCP-1, and IL-6 in THP-1
      macrophages.
AB  - Macrophages accumulated in the arterial intima play an important role in the
      development of atherosclerosis by producing a large number of proinflammatory
      cytokines which accelerate the disease. Recent studies show that adipophilin
      might be involved in inflammatory processes in macrophages. In this study, we
      observe the effect of adipophilin on proinflammatory cytokine expression and
      secretion in THP-1 macrophages. SiRNA and adipophilin gene overexpression
      mediated by an pEGFP-C3 vector were used to observe the effect of adipophilin on
      proinflammatory cytokines in THP-1 macrophages in vitro. Realtime PCR and enzyme
      linked immunosorbent assay (ELISA) were applied to detect the production of tumor
      necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein 1 (MCP-1),
      and interleukin-6 (IL-6). It was found that acetylated low-density lipoprotein
      (AcLDL), pioglitazone [a peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist] increased adipophilin expression in macrophages, while
      glucose had no such affect. It was also shown that adipophilin augments TNF
      alpha, MCP-1, and IL-6 expression in AcLDL induced macrophages. Our results
      suggest that adipophilin augment inflammation in macrophages, which might be one
      role of adipophilin in atherosclerosis.

PMID- 19851832
TI  - Downregulation of CREB-binding protein expression sensitizes endothelial cells to
      serum-deprived apoptosis: important role of nitric oxide.
AB  - Endothelium-derived nitric oxide (NO) is a cytoprotective molecule to prevent
      endothelial cells (ECs) from apoptosis. CREB-binding protein (CBP) is involved in
      the apoptotic pathway in several tumor cells, however, little is known whether
      CBP is associated with apoptosis in ECs and the apoptotic effect of CBP on ECs is
      regulated by NO. Therefore, the purpose of the present study was to investigate
      whether silencing CBP expression could affect the sensitivity of ECs toward
      apoptotic stimuli and determined the role of NO. In this study, we found that
      when CBP expression was silenced by RNA interference, ECs were more prone to
      apoptosis under serum deprivation, whereas the apoptosis was not significantly
      induced in the serum-containing condition. The increased apoptosis is paralleled
      by a reduction of NO, and the apoptosis was reversed by NO donors, suggesting an
      important role of NO. Furthermore, CBP silencing decreased NO production by
      downregulating the endothelial NO synthase (eNOS) expression in a dose-dependent
      manner. These results indicated that CBP silencing is associated with decreased
      eNOS expression and NO production, and therefore concomitantly increased the
      sensitivity of ECs toward apoptosis.

PMID- 19851833
TI  - Ectopic expression of hC/EBPs in breast tumor cells induces apoptosis.
AB  - CCAAT/enhancer binding proteins (C/EBPs) are a group of transcription factors
      which have been implicated in cellular proliferation, terminal differentiation,
      and apoptosis in a variety of tissues including mammary gland. Owing to its role
      in various cellular functions, inactivation of C/EBP proteins is central to the
      pathogenesis of many disorders. Recent reports suggest that expression as well as
      function of C/EBP proteins is deregulated in breast tumors. Although, role of
      C/EBPs in growth arrest in mammary tissues has been studied in much detail; their
      role in apoptosis is relatively less explored. In the present study, we have
      assessed if breast tumors evade apoptosis and grow faster by down regulating and
      inhibiting the C/EBP proteins, C/EBPalpha in particular. Our data shows that
      ectopic expression of human C/EBPs in breast tumor cells inhibits proliferation
      and induces apoptosis which is likely to be associated with caspase dependent
      pathway.

PMID- 19851834
TI  - Histamine stimulates human lung fibroblast migration.
AB  - Histamine is a potent mediator in allergic inflammatory processes and is released
      by basophils and mast cells. The aim of this study was to investigate the effect
      of histamine on in vitro migration of human fetal lung fibroblasts (HFL-1) to
      human plasma fibronectin (HFn), a chemoattractant. Using the blindwell chamber
      technique, histamine alone had no chemotactic activity. However, histamine
      augmented HFn-induced HFL-1 migration at concentrations ranging between 0 and 10(
      7) M (290.6 +/- 20.8%) (P < 0.05). The concentration-response was bell-shaped.
      The effect of histamine increased with time. The stimulatory effect of histamine
      on HFL-1 migration was inhibited by an H4 receptor antagonist, JNJ7777120 (10(-5)
      M). Histamine's effect was also inhibited by pertussis toxin (50 ng/ml), showing
      that the effect was mediated by the H4 receptor. This study demonstrated that
      histamine has the potential to stimulate human lung fibroblast migration, and
      thus may contribute to regulation of wound healing and the development of
      fibrotic disorders of the lung.

PMID- 19851836
TI  - Analytical approaches to uptake and release of hydrogel-associated FGF-2.
AB  - Strategies to control the delivery of growth factors are critically important in
      the design of advanced biomaterials. In this study we investigated the binding
      and release of fibroblast growth factor 2 (FGF-2) to/from a biohybrid hydrogel
      matrix by four independent analytical methods: radioisotope and fluorescence
      labeling, amino acid analysis and Enzyme-Linked Immunosorbent Assays (ELISA). The
      compared analyses provided qualitatively similar uptake characteristics while the
      results of the FGF-2 quantification strongly depended on the particular
      experimental conditions. The release kinetics of FGF-2 from the gels could be
      monitored sensitively by (125)I labeling and by ELISA-techniques. The latter
      method was concluded to be advantageous since it permits the application of
      unmodified ("native") growth factors.

PMID- 19851837
TI  - Synergistic effect of hydrophobic and anionic surface groups triggers blood
      coagulation in vitro.
AB  - Biomaterial induced coagulation encompasses plasmatic and cellular processes. The
      functional loss of biomedical devices possibly resulting from these thrombotic
      reactions motivates the need for a better understanding of processes occurring at
      blood-biomaterial interfaces. Well defined model surfaces providing specific
      chemical-physical properties (self assembled monolayers (SAMs)) displaying
      hydrophobic or/and acidic terminal groups were used to uncover initial mechanisms
      of biomaterial induced coagulation. We investigated the influence of electrical
      charge and wettability on platelet- and contact activation, the two main actors
      of blood coagulation, which are often considered as separate mechanisms in
      biomaterials research. Our results show a dependence of contact activation on
      acidic surface groups and a correlation of platelet adhesion to surface
      hydrophobicity. Clot formation resulting from the interplay of blood platelets
      and contact activation was only found on surfaces combining both acidic and
      hydrophobic surface groups but not on monolayers displaying extreme
      hydrophobic/acidic properties.

PMID- 19851835
TI  - Opening of the mitoKATP channel and decoupling of mitochondrial complex II and
      III contribute to the suppression of myocardial reperfusion hyperoxygenation.
AB  - Diazoxide, a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel opener,
      protects the heart from ischemia-reperfusion injury. Diazoxide also inhibits
      mitochondrial complex II-dependent respiration in addition to its preconditioning
      effect. However, there are no prior studies of the role of diazoxide on post
      ischemic myocardial oxygenation. In the current study, we determined the effect
      of diazoxide on the suppression of post-ischemic myocardial tissue
      hyperoxygenation in vivo, superoxide (O(2)(-*)) generation in isolated
      mitochondria, and impairment of the interaction between complex II and complex
      III in purified mitochondrial proteins. It was observed that diazoxide totally
      suppressed the post-ischemic myocardial hyperoxygenation. With succinate but not
      glutamate/malate as the substrate, diazoxide significantly increased
      ubisemiquinone-dependent O(2)(-*) generation, which was not blocked by 5-HD and
      glibenclamide. Using a model system, the super complex of succinate-cytochrome c
      reductase (SCR) hosting complex II and complex III, we also observed that
      diazoxide impaired complex II and its interaction with complex III with no effect
      on complex III. UV-visible spectral analysis revealed that diazoxide decreased
      succinate-mediated ferricytochrome b reduction in SCR. In conclusion, our results
      demonstrated that diazoxide suppressed the in vivo post-ischemic myocardial
      hyperoxygenation through opening the mitoK(ATP) channel and ubisemiquinone
      dependent O(2)(-*) generation via inhibiting mitochondrial complex II-dependent
      respiration.

PMID- 19851838
TI  - Preparation and characterization of porous alginate scaffolds containing various
      amounts of octacalcium phosphate (OCP) crystals.
AB  - The present study was designed to investigate whether the amount of octacalcium
      phosphate (OCP) affects the characteristics of alginate (Alg)/OCP scaffolds
      regarding the pore formation and its distribution, and the thermodynamic
      stability from OCP to hydroxyapatite (HA) in an in vitro physiological
      environment. Alg/OCP composites with weight ratios of 100/0, 75/25, 50/50, and
      25/75 were prepared through mixing the ground synthesized OCP crystals with an
      Alg solution and applying lyophilization. Analysis of X-ray diffraction, Fourier
      transform infrared (FTIR) spectroscopy, and mercury intrusion porosimetry
      verified that the crystalline phase of OCP and the porosities were retained
      regardless of the OCP amount. On the other hand, the elastic modulus, determined
      by mechanical testing, and, interestingly, the pore size increased with
      increasing the OCP amount. The immersion of the composites in a simulated body
      fluid up to 14 days revealed that OCP in Alg matrices tends to convert to HA with
      enhancing the calcium consumption depending on the OCP amount. The results
      indicated that the inclusion of OCP crystals in the Alg matrix by the mixing
      process controls the character of the pore distribution in Alg/OCP composites
      while maintaining the transitory nature of OCP.

PMID- 19851839
TI  - Influence of telopeptides, fibrils and crosslinking on physicochemical properties
      of type I collagen films.
AB  - Type I collagen is widely used in various different forms for research and
      commercial applications. Different forms of collagen may be classified according
      to their source, extraction method, crosslinking and resultant ultrastructure. In
      this study, afibrillar and reconstituted fibrillar films, derived from acid
      soluble and pepsin digested Type I collagen, were analysed using Lateral Force
      Microscopy (LFM), Fourier Transform Infra-Red Spectroscopy (FTIR), Differential
      Scanning Calorimetry (DSC) and enzymatic stability assays to asses the influence
      of telopeptides, fibrils and crosslinking. LFM proved to be a useful technique to
      confirm an afibrillar/fibrillar ultrastructure and to elucidate fibril diameters.
      FTIR has proved insensitive to ultrastructural differences involving telopeptides
      and fibrils. DSC results showed a significant increase in T(d) for crosslinked
      samples (+22-28 degrees C), and demonstrated that the thermal behaviour of
      hydrated, afibrillar films is more akin to reconstituted fibrillar films than
      monomeric solutions. The enzymatic stability assay has provided new evidence to
      show that afibrillar films of Type I collagen can be significantly more resistant
      to collagenase (by up to 3.5 times), than reconstituted fibrillar films, as a
      direct consequence of the different spatial arrangement of collagen molecules. A
      novel mechanism for this phenomenon is proposed and discussed. Additionally, the
      presence of telopeptide regions in afibrillar tropocollagen samples has been
      shown to increase resistance to collagenase by greater than 3.5 times compared to
      counterpart afibrillar atelocollagen samples. One-factor ANOVA analysis, with
      Fisher's LSD post-hoc test, confirms these key findings to be of statistical
      significance (P < 0.05). The profound physicochemical effects of collagen
      ultrastructure demonstrated in this study reiterates the need for comprehensive
      materials disclosure and classification when using these biomaterials.

PMID- 19851840
TI  - How is wettability of titanium surfaces influenced by their preparation and
      storage conditions?
AB  - The effect of two different etching procedures with inorganic acids (HSE and CSE)
      one using additionally strongly oxidising conditions due to the presence of
      CrO(3) (CSE)-and consecutive storage conditions (dry methanol and air) for
      previous corundum blasted titanium surfaces is compared with respect to their
      wettability behaviour and the potential of the etching processes for removing
      remaining blasting material. The etching procedures result in distinct different
      surface morphologies. Whereas the HSE surface shows sub-mm to sub-mum structures
      but neither porosity nor undercuts, the CSE surface is extremely rugged and
      porous with structures protruding the more homogeneously attacked areas by
      several micrometers. By EDX analysis both remaining blasting material and
      chromium and sulphur from the etching treatment has been detected on the CSE
      surfaces only. Both surfaces states show super-hydrophilic behaviour immediately
      after etching and storage up to 28 days in dry methanol. Whereas contact with air
      does not change super-hydrophilicity for the CSE samples, wettings angles of the
      HSE samples increase within minutes and reach about angles of about 60 degrees
      and 90 degrees after one and 2 days exposure to air, respectively. The increasing
      hydrophobicity is discussed with respect to the formation of a surface coverage
      from hydrocarbons originating from aromatic compounds present in traces in air.

PMID- 19851841
TI  - Biomimetic calcium phosphate coating on Ti wires versus flat substrates:
      structure and mechanism of formation.
AB  - Biomimetic calcium phosphate (Ca-P) coatings improve the osteoconductivity of
      orthopedic implants and show promise as slow delivery systems for growth factors.
      This paper compares the structure and composition of biomimetic coatings on flat
      titanium coupons and on Ti wires/thin pins that are often used as model implants
      in small animal in vivo models. Ca-P coatings were grown on alkali-treated Ti
      substrates using a two-step deposition procedure. The coatings on wires consisted
      of a surface layer of octacalcium phosphate (OCP) and a layer of Ca-deficient
      hydroxyapatite (CDHA) underneath. The coating thickness and the proportion of
      CDHA decreased with increasing wire diameter. The coatings on flat coupons were
      the thinnest, and were comprised almost entirely of OCP. A mechanism of
      successive formation of the CDHA and OCP phases based on the interplay between
      nucleation, growth and hydrolysis of OCP crystals as a function of changing local
      supersaturation is proposed.

PMID- 19851842
TI  - In vitro bioactivity of sol-gel-derived hydroxyapatite particulate nanofiber
      modified titanium.
AB  - A chemically-etched titanium surface was modified by electrospinning a sol-gel
      derived hydroxyapatite (HAp) that was subjected to calcination within the
      temperature range of 200-1400 degrees C in the normative atmospheric condition.
      After heat treatment, crystal structures of the filmed titanium oxide and HAp on
      the titanium's surface were identified using wide-angle X-ray diffraction. A
      highly porous layer of HAp was found to have formed on the oxidized titanium
      surfaces. The surfaces of three different samples; (1) electrospun HAp, (2) HAp
      calcined at 600 degrees C, and (3) HAp calcined at 800 degrees C, were
      investigated for their ability to foster promotion, proliferation, and
      differentiation of human osteoblasts (HOB) (in the 9th passage) in vitro up to 6
      days. Among the three samples, cells cultured on the HAp calcined at 800 degrees
      C titanium surfaces displayed the best results with regard to adhesion, growth,
      and proliferation of HOB. This novel method for fabrication of titanium
      substrates would provide a promising improvement for titanium-based medical
      devices over the current standards, which lack such substrates. These titanium
      substrates explicitly provide enhanced HOB proliferation in terms of both desired
      surface properties and their produced bulk quantity.

PMID- 19851844
TI  - Application of prepared waterborne polyurethane extended with chitosan to impart
      antibacterial properties to acrylic fabrics.
AB  - In this study, isophorone diisocyanate (IPDI), 2,2-bis (hydroxylmethyl)-propionic
      acid and polyethylene glycol (PEG) were employed to polymerize waterborne
      polyurethane. The polyurethane prepolymer was extended with chitosan of two
      different molecular weight (100,000 and 150,000), and used as finishing agent for
      acrylic fabrics. The antibacterial activity of the acrylic fabric treated with
      the polyurethane-chitosan solution was improved even after 15 washing times.
      Pretreatment of acrylic fabrics with hydrazine hydrate was found to improve the
      uptake of the polymer by the fabric. The effects of hydrazine and polyurethane
      treatments on some of the inherent properties of acrylic were assessed. The
      functional groups of polyurethane prepolymer as well as polyurethane extended
      with chitosan were confirmed with the analysis of the spectra of Fourier
      transform infrared spectroscopy (FT-IR).

PMID- 19851843
TI  - Kinetics of fluoride ion release from dental restorative glass ionomer cements:
      the influence of ultrasound, radiant heat and glass composition.
AB  - To compare the effect of ultrasonic setting with self curing on fluoride release
      from conventional and experimental dental glass ionomer cements. To compare hand
      mixed and capsule mixing and the effect of replacing some of the reactive glass
      with zirconia. In a novel material which advocated using radiant heat to cure it,
      to compare the effect of this with ultrasound. To evaluate the effect of
      ultrasound on a glass ionomer with fluoride in the water but not in the glass. 10
      samples of each cement were ultrasonically set for 55 s; 10 controls self cured
      for 6 min. Each was placed in 10 ml of deionised water which was changed at 1, 3,
      7, 14, 21, 28 days. The solution fluoride content was measured using a selective
      ion electrode. All ultrasound samples released more fluoride than the controls.
      Release patterns were similar; after a few days, cumulative fluoride was linear
      with respect to t(1/2). Slope and intercept of linear regression plots increased
      with ultrasound. With radiant heat the cement released less fluoride than
      controls. The effect of ultrasound on cement with F in water increased only slope
      not intercept. Zirconia addition enhances fluoride release although the cement
      fluorine content is reduced. Comparison of capsule and hand mixing showed no
      consistent effect on fluoride release. Ultrasound enhances fluoride release from
      GICs. As heat has an opposite effect the heat from ultrasound is not its only
      action. The lesser effect on cement with fluoride only in the water indicates
      that of ultrasound enhances fluoride release from glass.

PMID- 19851845
TI  - Injectability of brushite-forming Mg-substituted and Sr-substituted alpha-TCP
      bone cements.
AB  - The influence of magnesium- and strontium-substitutions on injectability and
      mechanical performance of brushite-forming alpha-TCP cements has been evaluated
      in the present work. The effects of Mg- and Sr-substitutions on crystalline phase
      composition and lattice parameters were determined through quantitative X-ray
      phase analysis and structural Rietveld refinement of the starting calcium
      phosphate powders and of the hardened cements. A noticeable dependence of
      injectability on the liquid-to-powder ratio (LPR), smooth plots of extrusion
      force versus syringe plunger displacement and the absence of filter pressing
      effects were observed. For LPR values up to 0.36 ml g(-1), the percentage of
      injectability was always higher and lower for Mg-containing cements and for Sr
      containing cements, respectively, while all the pastes could be fully injected
      for LPR > 0.36 ml g(-1). The hardened cements exhibited relatively high wet
      compressive strength values (~17-25 MPa) being the Sr- and Mg-containing cements
      the strongest and the weakest, respectively, holding an interesting promise for
      uses in trauma surgery such as for filling bone defects and in minimally invasive
      techniques such as percutaneous vertebroplasty to fill lesions and strengthen the
      osteoporotic bone.

PMID- 19851847
TI  - Time resolved fluorescence and energy transfer analysis of Nd(3+)-Yb (3+)-Er (3+)
      triply-doped Ba-Al-metaphosphate glasses for an eye safe emission (1.54 microm).
AB  - This paper reports on the preparation and systematic analysis of energy transfer
      mechanisms in Nd(3+)-Yb(3+)-Er(3+) co-doped new series of barium-alumino
      metaphosphate glasses. The time resolved fluorescence of Nd(3+) in triply doped
      Ba-Al-metaphosphate glasses have revealed that, Yb(3+) ions could function as
      quite efficient bridge for an energy transfer between Nd(3+) and Er(3+) ions. As
      a result, a fourfold emission enhancement at 1.54 mum of Er(3+) ions has been
      achieved through an excitation of (4)F(5/2) level of Nd(3+) at 806 nm for the
      glass having 3 mol% Yb(3+) with an energy transfer efficiency reaching up to 94%.
      Decay of donor (Nd(3+)) ion fluorescence has been analyzed based on theoretical
      models such as direct energy transfer model (Inokuti-Hirayama) and migration
      assisted energy transfer models (Burshtein's hopping and Yokota-Tanimoto's
      diffusion). The corresponding energy transfer parameters have been evaluated and
      discussed. Primarily, electrostatic dipole-dipole (s approximately 6)
      interactions are found to be responsible for the occurrence of energy transfer
      process in theses glasses.

PMID- 19851846
TI  - Positively-charged, porous, polysaccharide nanoparticles loaded with anionic
      molecules behave as 'stealth' cationic nanocarriers.
AB  - PURPOSE: Stealth nanoparticles are generally obtained after modifying their
      surface with hydrophilic polymers, such as PEG. In this study, we analysed the
      effect of a phospholipid (DG) or protein (BSA) inclusion in porous cationic
      polysaccharide (NP(+)) on their physico-chemical structure and the effect on
      complement activation. METHODS: NP(+)s were characterised in terms of size, zeta
      potential (zeta) and static light scattering (SLS). Complement consumption was
      assessed in normal human serum (NHS) by measuring the residual haemolytic
      capacity of the complement system. RESULTS: DG loading did not change their size
      or zeta, whereas progressive BSA loading lightly decreased their zeta. An
      electrophoretic mobility analysis study showed the presence of two differently
      charged sublayers at the NP(+) surface which are not affected by DG loading.
      Complement system activation, studied via a CH50 test, was suppressed by DG or
      BSA loading. We also demonstrated that NP(+)s could be loaded by a polyanionic
      molecule, such as BSA, after their preliminary filling by a hydrophobic molecule,
      such as DG. CONCLUSION: These nanoparticles are able to absorb large amounts of
      phospholipids or proteins without change in their size or zeta potential.
      Complement studies showed that stealth behaviour is observed when they are loaded
      and saturated either with anionic phospholipid or proteins.

PMID- 19851848
TI  - Preparation and time-resolved luminescence bioassay application of multicolor
      luminescent lanthanide nanoparticles.
AB  - Because highly luminescent lanthanide compounds are limited to Eu(3+) and Tb(3+)
      compounds with red (Eu, approximately 615 nm) and green (Tb, approximately 545
      nm) emission colors, the development and application of time-resolved
      luminescence bioassay technique using lanthanide-based multicolor luminescent
      biolabels have rarely been investigated. In this work, a series of lanthanide
      complexes covalently bound silica nanoparticles with an excitation maximum
      wavelength at 335 nm and red, orange, yellow and green emission colors has been
      prepared by co-binding different molar ratios of luminescent Eu(3+)-Tb(3+)
      complexes with a ligand N,N,N(1),N(1)-(4'-phenyl-2,2':6',2''-terpyridine-6,6''
      diyl)bis(methylenenitrilo) tetrakis (acetic acid) inside the silica
      nanoparticles. The nanoparticles characterized by transmission electron
      microscopy and luminescence spectroscopy methods were used for streptavidin
      labeling, and time-resolved fluoroimmunoassay (TR-FIA) of human prostate-specific
      antigen (PSA) as well as time-resolved luminescence imaging detection of an
      environmental pathogen, Giardia lamblia. The results demonstrated the utility of
      the new multicolor luminescent lanthanide nanoparticles for time-resolved
      luminescence bioassays.

PMID- 19851849
TI  - Mahfouz H. Zaki, MD, MPH, DrPH.

PMID- 19851850
TI  - Genetic counselors' perceived responsibilities regarding reproductive issues for
      patients at risk for Huntington disease.
AB  - Research indicates that health care professionals' attitudes may affect patients'
      decisions regarding prenatal Huntington Disease testing, but few studies have
      sampled genetic counselors. In this qualitative study, genetic counselors
      described their experiences counseling individuals at risk for HD regarding
      reproductive decision-making. Five major research questions were investigated: 1)
      What are genetic counselor responsibilities? 2) What issues arise for patients
      and counselors? 3) How do counselors reconcile prenatal testing with
      presymptomatic testing? 4) To what extent are counselors' initial expectations of
      at-risk patients' beliefs and behaviors met? and 5) What advice would counselors
      offer to novice practitioners about working with this patient population? Fifteen
      genetic counselors experienced in counseling individuals at risk for HD
      participated in a semi-structured phone interview that yielded several themes.
      For example, participants identified their primary responsibility as information
      provision; less prevalent were psychosocial support and facilitating decision
      making. The most common ethical challenge was testing prenatally for HD which
      also results in presymptomatic testing of minors. Participants were divided about
      how directive to be in response to this ethical issue and about termination of a
      gene positive pregnancy.

PMID- 19851852
TI  - Metabolic brain disease. Editorial.

PMID- 19851851
TI  - Brain iron homeostasis, the choroid plexus, and localization of iron transport
      proteins.
AB  - Maintenance of appropriate iron homeostasis in the brain is important, but the
      mechanisms involved in brain iron uptake are incompletely understood. Here, we
      have analyzed where messenger RNAs that encode iron transport proteins are
      expressed in the brain, using the Allen Brain atlas, and we conclude that several
      important iron transporters are highly expressed in the choroid plexus. Based on
      recent estimates of the surface area of the choroid plexus and on MRI imaging
      studies of manganese uptake in the brain, we propose that the choroid plexus may
      have a much greater role than has been previously appreciated in brain iron
      transport.

PMID- 19851854
TI  - An explanation for the shape of the human penis.

PMID- 19851853
TI  - Genetic characterization of 2006-2008 isolates of Chikungunya virus from Kerala,
      South India, by whole genome sequence analysis.
AB  - Chikungunya virus (CHIKV), a positive-stranded alphavirus, causes epidemic
      febrile infections characterized by severe and prolonged arthralgia. In the
      present study, six CHIKV isolates (2006 RGCB03, RGCB05; 2007 RGCB80, RGCB120;
      2008 RGCB355, RGCB356) from three consecutive Chikungunya outbreaks in Kerala,
      South India, were analyzed for genetic variations by sequencing the 11798 bp
      whole genome of the virus. A total of 37 novel mutations were identified and they
      were predominant in the 2007 and 2008 isolates among the six isolates studied.
      The previously identified E1 A226V critical mutation, which enhances mosquito
      adaptability, was present in the 2007 and 2008 samples. An important observation
      was the presence of two coding region substitutions, leading to nsP2 L539S and E2
      K252Q change. These were identified in three isolates (2007 RGCB80 and RGCB120;
      2008 RGCB355) by full-genome analysis, and also in 13 of the 31 additional
      samples (42%), obtained from various parts of the state, by sequencing the
      corresponding genomic regions. These mutations showed 100% co-occurrence in all
      these samples. In phylogenetic analysis, formation of a new genetic clade by
      these isolates within the East, Central and South African (ECSA) genotypes was
      observed. Homology modeling followed by mapping revealed that at least 20 of the
      identified mutations fall into functionally significant domains of the viral
      proteins and are predicted to affect protein structure. Eighteen of the
      identified mutations in structural proteins, including the E2 K252Q change, are
      predicted to disrupt T-cell epitope immunogenicity. Our study reveals that CHIK
      virus with novel genetic changes were present in the severe Chikungunya outbreaks
      in 2007 and 2008 in South India.

PMID- 19851855
TI  - The DSM diagnostic criteria for vaginismus.
AB  - Vaginal spasm has been considered the defining diagnostic characteristic of
      vaginismus for approximately 150 years. This remarkable consensus, based
      primarily on expert clinical opinion, is preserved in the DSM-IV-TR. The
      available empirical research, however, does not support this definition nor does
      it support the validity of the DSM-IV-TR distinction between vaginismus and
      dyspareunia. The small body of research concerning other possible ways or methods
      of diagnosing vaginismus is critically reviewed. Based on this review, it is
      proposed that the diagnoses of vaginismus and dyspareunia be collapsed into a
      single diagnostic entity called "genito-pelvic pain/penetration disorder." This
      diagnostic category is defined according to the following five dimensions:
      percentage success of vaginal penetration; pain with vaginal penetration; fear of
      vaginal penetration or of genito-pelvic pain during vaginal penetration; pelvic
      floor muscle dysfunction; medical co-morbidity.

PMID- 19851856
TI  - From mental disorder to iatrogenic hypogonadism: dilemmas in conceptualizing
      gender identity variants as psychiatric conditions.
AB  - The categorization of gender identity variants (GIVs) as "mental disorders" in
      the Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American
      Psychiatric Association is highly controversial among professionals as well as
      among persons with GIV. After providing a brief history of GIV categorizations in
      the DSM, this paper presents some of the major issues of the ongoing debate: GIV
      as psychopathology versus natural variation; definition of "impairment" and
      "distress" for GID; associated psychopathology and its relation to stigma; the
      stigma impact of the mental-disorder label itself; the unusual character of "sex
      reassignment surgery" as a psychiatric treatment; and the consequences for health
      and mental-health services if the disorder label is removed. Finally, several
      categorization options are examined: Retaining the GID category, but possibly
      modifying its grouping with other syndromes; narrowing the definition to
      dysphoria and taking "disorder" out of the label; categorizing GID as a
      neurological or medical rather than a psychiatric disorder; removing GID from
      both the DSM and the International Classification of Diseases (ICD); and creating
      a special category for GIV in the DSM. I conclude that-as also evident in other
      DSM categories-the decision on the categorization of GIVs cannot be achieved on a
      purely scientific basis, and that a consensus for a pragmatic compromise needs to
      be arrived at that accommodates both scientific considerations and the service
      needs of persons with GIVs.

PMID- 19851857
TI  - Biogenic amines in Rett syndrome: the usual suspects.
AB  - Rett syndrome (RTT) is a severe postnatal neurological disorder caused by
      mutations in the methyl-CpG binding protein 2 (MECP2) gene. In affected children,
      most biological parameters, including brain structure, are normal (although
      acquired microcephaly is usually present). However, in recent years, a deficit in
      bioaminergic metabolism has been identified at the cellular and molecular levels,
      in more than 200 patients. Recently available transgenic mouse strains with a
      defective Mecp2 gene also show abnormalities, strongly suggesting that there is a
      direct link between the function of the MECP2 protein and the metabolism of
      biogenic amines. Biogenic amines appear to have an important role in the
      pathophysiology of Rett syndrome, for several reasons. Firstly, biogenic amines
      modulate a large number of autonomic and cognitive functions. Secondly, many of
      these functions are affected in RTT patients. Thirdly, biogenic amines are the
      only neurotransmitters that have repeatedly been found to be altered in RTT
      patients. Importantly, pharmacological interventions can be envisaged to try to
      counteract the deficits observed. Here, we review the available human and mouse
      data and present how they have been and could be used in the development of
      pharmacological treatments for children affected by the syndrome. Given our
      current knowledge and the tools available, modulating biogenic amine metabolism
      may prove to be the most promising strategy for improving the life quality of
      Rett syndrome patients in the short term.

PMID- 19851858
TI  - Screening for clonal hematopoiesis as a predictive marker for development of
      therapy-related myeloid neoplasia (t-MN) following neoadjuvant therapy for breast
      cancer: a Southwest Oncology Group study (S0012).
AB  - A serious complication associated with breast cancer treatment is the increased
      risk for development of therapy-related myeloid neoplasms (t-MN). To determine
      whether dose-intensive adjuvant regimens for breast cancer induce genetic damage
      to hematopoietic stem cells, defined by the emergence of clonal hematopoiesis,
      and whether detection of clonal hematopoiesis could be used as an early marker
      for the subsequent development of t-MN, the Southwest Oncology Group designed a
      pilot clonality investigation to estimate the incidence of clonal hematopoiesis
      during and shortly after completion of the dose intensive neoadjuvant regimens
      for high-risk breast cancer patients. Peripheral blood samples from 274 patients
      obtained prior to treatment, at time of surgery, and at 6 and 12 months post
      surgery were examined by two different clonality assays: the HUMARA (HUMan
      Androgen Receptor) assay to estimate the incidence of early genetic damage by
      clonal proliferation, and microsatellite instability (MSI) testing to screen for
      LOH or defective DNA mismatch repair mechanisms. Clonal hematopoiesis was
      negative in 93.5% of the samples analyzed. Five patients showed a HUMARA
      positive/MSI-negative pattern, and no patients showed a HUMARA-negative/MSI
      positive pattern. With a median follow-up of 3.1 years, one patient in our study
      developed t-AML at 3 years 5 months after randomization. Our results indicate
      that clonal hematopoiesis assays performed within the 2 years following dose
      intensive neoadjuvant therapy failed to identify an emerging clonal hematopoietic
      stem cell population. Longer clinical follow-up will be necessary to define
      better the positive predictive value of detecting clonal hematopoiesis in the
      HUMARA+/MSI- cases.

PMID- 19851860
TI  - High ACAT1 expression in estrogen receptor negative basal-like breast cancer
      cells is associated with LDL-induced proliferation.
AB  - The specific role of dietary fat in breast cancer progression is unclear,
      although a low-fat diet was associated with decreased recurrence of estrogen
      receptor alpha negative (ER(-)) breast cancer. ER(-) basal-like MDA-MB-231 and
      MDA-MB-436 breast cancer cell lines contained a greater number of cytoplasmic
      lipid droplets compared to luminal ER(+) MCF-7 cells. Therefore, we studied lipid
      storage functions in these cells. Both triacylglycerol and cholesteryl ester (CE)
      concentrations were higher in the ER(-) cells, but the ability to synthesize CE
      distinguished the two types of breast cancer cells. Higher baseline, oleic acid-
      and LDL-stimulated CE concentrations were found in ER(-) compared to ER(+) cells.
      The differences corresponded to greater mRNA and protein levels of acyl
      CoA:cholesterol acyltransferase 1 (ACAT1), higher ACAT activity, higher caveolin
      1 protein levels, greater LDL uptake, and lower de novo cholesterol synthesis in
      ER(-) cells. Human LDL stimulated proliferation of ER(-) MDA-MB-231 cells, but
      had little effect on proliferation of ER(+) MCF-7 cells. The functional
      significance of these findings was demonstrated by the observation that the ACAT
      inhibitor CP-113,818 reduced proliferation of breast cancer cells, and
      specifically reduced LDL-induced proliferation of ER(-) cells. Taken together,
      our studies show that a greater ability to take up, store and utilize exogenous
      cholesterol confers a proliferative advantage to basal-like ER(-) breast cancer
      cells. Differences in lipid uptake and storage capability may at least partially
      explain the differential effect of a low-fat diet on human breast cancer
      recurrence.

PMID- 19851859
TI  - High-risk human papilloma virus infection, tumor pathophenotypes, and BRCA1/2 and
      TP53 status in juvenile breast cancer.
AB  - Juvenile breast cancer is rare and poorly known. We studied a series of five
      breast cancer patients diagnosed within 25 years of age that included two
      adolescents, 12- and 15-years-old, and 3 young women, 21-, 21-, and 25-years-old,
      respectively. All cases were scanned for germline mutations along the entire
      BRCA1/2 coding sequences and TP53 exons 4-10, using protein truncation test,
      denaturing high performance liquid chromatography and direct sequencing. Paraffin
      embedded primary tumors (available for 4/5 cases), and a distant metastasis (from
      the 15-years-old) were characterized for histological and molecular tumor
      subtype, human papilloma virus (HPV) types 16/18 E6 sequences and tumor
      associated mutations in TP53 exons 5-8. A BRCA2 germline mutation (p.Ile2490Thr),
      previously reported in breast cancer and, as compound heterozygote, in Fanconi
      anemia, was identified in the 21-year-old patient diagnosed after pregnancy,
      negative for cancer family history. The tumor was not available for study. Only
      germline polymorphisms in BRCA1/2 and/or TP53 were detected in the other cases.
      The tumors of the 15- and 12-years-old were, respectively, classified as glycogen
      rich carcinoma with triple negative subtype and as secretory carcinoma with basal
      subtype. The tumors of the 25-year-old and of the other 21-year-old were,
      respectively, diagnosed as infiltrating ductal carcinoma with luminal A subtype
      and as lobular carcinoma with luminal B subtype. No somatic TP53 mutations were
      found, but tumor-associated HPV 16 E6 sequences were retrieved from the 12- and
      25-year-old, while both HPV 16 and HPV 18 E6 sequences were found in the tumor of
      the 15-year-old and in its associated metastasis. Blood from the 15- and 25-year
      old, diagnosed with high-stage disease, resulted positive for HPV 16 E6. All the
      HPV-positive cases were homozygous for arginine at TP53 codon 72, a genotype
      associated with HPV-related cancer risk, and the tumors showed p16(INK4A)
      immunostaining, a marker of HPV-associated cancers. Notably menarche at 11 years
      was reported for the two adolescents, while the 25-year-old was diagnosed after
      pregnancy and breast-feeding. Our data suggest that high-risk HPV infection is
      involved in a subset of histopathologically heterogeneous juvenile breast
      carcinomas associated with menarche or pregnancy and breast-feeding. Furthermore
      we implicate BRCA2 in a juvenile breast carcinoma diagnosed at 21 years of age, 4
      years after an early full-term pregnancy, in absence of cancer family history.

PMID- 19851861
TI  - Meta-analysis of vitamin D, calcium and the prevention of breast cancer.
AB  - Vitamin D and calcium intake have been suggested to have protective effects
      against breast cancer; however, the data have been inconclusive. The present meta
      analysis examined the overall effects of vitamin D intake, circulating 25(OH)D
      and 1alpha,25(OH)(2)D levels, and calcium intake on breast cancer risk. Data from
      11 studies on vitamin D intake, 7 studies on circulating 25(OH)D levels, 3
      studies of circulating 1alpha,25(OH)(2)D levels, and 15 studies on calcium intake
      and breast cancer risk were included in this analysis. From the meta-analysis,
      there was a significant inverse relationship between vitamin D intake and breast
      cancer risk, with an overall relative risk (RR) of high versus low vitamin D
      intake for breast cancer of 0.91 (95% CI = 0.85-0.97). The highest quantile of
      circulating 25(OH)D was found to be associated with a 45% (OR = 0.55, 95% CI =
      0.38-0.80) decrease in breast cancer when compared with the lowest quantile. No
      significant association for the circulating 1alpha,25(OH)(2)D level and breast
      cancer was found (OR = 0.99, 95% CI = 0.68-1.44). For calcium, a 19% (RR = 0.81,
      95% CI = 0.72-0.90) decrease in breast cancer risk was found for those with
      highest quantile of calcium intake compared to the lowest quantile. These results
      provide strong evidence that vitamin D and calcium have a chemopreventive effect
      against breast cancer.

PMID- 19851862
TI  - The association of metabolic syndrome with triple-negative breast cancer.
AB  - Metabolic syndrome, a conglomerate of obesity, insulin resistance, dyslipidemia,
      and hypertension has been linked with an increased risk of breast cancer. We
      investigated the possible association of highly aggressive triple-negative breast
      cancer and the metabolic syndrome. Information on metabolic syndrome components
      and tumor characteristics were reviewed in a cohort of 176 patients (including 86
      triple-negatives). Retrospective comparison was performed using Pearson Chi
      square test or Student's t test for data analysis. A statistically significant
      association of triple-negative breast cancer with the metabolic syndrome was
      observed. In accordance with the NCEP (National Cholesterol Education Program)
      definition, 58.1% of triple-negative patients had metabolic syndrome compared to
      only 36.7% of non-triple-negative patients (P = 0.004). Consistently, by the AACE
      (American Association of Clinical Endocrinologists) criteria, 52.3% of triple
      negative patients had metabolic syndrome as compared to 34.4% of non-triple
      negative patients (P = 0.017). Blood glucose, triglyceride, and HDL levels but
      not hypertension or BMI (body mass index) showed significant independent
      association with triple-negative breast cancer. Additionally, triple-negative
      tumors displayed a significantly higher histological grade and relative paucity
      of ductal carcinoma in situ (DCIS) when compared to the non-triple-negative
      tumors (P < 0.001). Our study suggests that metabolic syndrome is significantly
      more prevalent in triple-negative breast cancer patients as opposed to non-triple
      negative patients. Furthermore, triple-negative breast cancer showed a
      significantly higher histological grade and a relative absence of DCIS. Whether
      the presence of metabolic syndrome preferentially increases the risk of
      developing triple-negative-breast cancer remains to be elucidated with future
      prospective studies.

PMID- 19851863
TI  - Evidence for a tumor promoting effect of high-fat diet independent of insulin
      resistance in HER2/Neu mammary carcinogenesis.
AB  - The mechanism of the association between breast cancer and obesity remains
      unknown. To investigate this mice over-expressing HER2/Neu in the mammary gland
      (MMTV-HER2/Neu) were fed either a high-fat diet (45% of calories) (HFD) or low
      fat diet (10%) (LFD) from 4 weeks of age and followed for up to 1 year, or
      sacrificed when a mammary tumor reached 1.5 cm. There was a small but significant
      increase in body weight on HFD (P < 0.05) and the HFD mice displayed a greater
      fat mass determined by MRI (P < 0.01). Mild glucose intolerance was observed from
      3 months of age on HFD, but insulin levels were not elevated. While the time of
      onset of a first tumor and tumor growth rates were not altered, mice on HFD had
      an earlier onset of a second tumor and a twofold greater incidence (LFD 25%, HFD
      54%) and a greater absolute number of multiple tumors (tumors/mouse, LFD 1.5 +/-
      0.25 vs. HFD 2.7 +/- 0.23, P < 0.01). Consistent with a lack of hyperinsulinemia,
      immunoblotting of skeletal muscle lysates from mice injected with insulin showed
      no insulin resistance determined by the phosphorylation of Akt/PKB. Similarly,
      there was no difference in basal or maximum insulin-stimulated phosphorylation of
      IRS-1/2, Akt/PKB, or p70 S6K in tumor cell lysates from HFD and LFD groups.
      Immunohistochemistry revealed no difference in tumor tissue staining for the
      proliferative marker, Ki67, between diets. These data indicate that HFD, in the
      absence of significant insulin resistance, mediates a tumor promoting, but not a
      tumor growth effect in this model of mammary carcinogenesis.

PMID- 19851864
TI  - Effects of extracellular polymeric and humic substances on chlorpyrifos
      bioavailability to Chironomus riparius.
AB  - The role of sediment organic matter quality and quantity for chlorpyrifos
      bioavailability was studied in experiments with Chironomus riparius larvae and
      with four types of organic matter; (1) commercially available extracellular
      polymeric substances (EPS), (2) EPS produced by sediment microbes, (3)
      commercially available humic substances and, (4) humic substances extracted from
      a boreal lake. The effects of each type of organic matter were assessed at three
      concentrations. We used a (14)C-tracer approach to quantify uptake of
      chlorpyrifos in the larvae, and the partitioning of the insecticide within the
      microcosm. Carbon-normalised larval uptake was reduced both by EPS and humic
      substances. However, the reduction in uptake was much greater for EPS than for
      humic substances: uptake was reduced by 94 and 88% for commercial and complex
      EPS, and by 59 and 57% for commercial and complex humic substances, respectively.
      We also found differences in chlorpyrifos uptake, and sediment concentrations
      between treatments with commercially available and complex polymers, suggesting
      that minor differences in the quality of relatively simple organic molecules can
      affect contaminant behaviour in ecotoxicological studies. Passive uptake in dead
      controls was 40% of that in living larvae. Therefore, both passive and digestive
      uptake were important processes for chlorpyrifos uptake by larvae. Our results
      show that both EPS and humic substances affect chlorpyrifos bioavailability to
      sediment biota negatively and contribute to the understanding of the processes
      that regulate organic contaminant bioavailability in aquatic environments.

PMID- 19851866
TI  - Protective effects of acetyl-L-carnitine on cisplatin cytotoxicity and oxidative
      stress in neuroblastoma.
AB  - The most widely used platinum-derived drug is cisplatin in neuroblastoma (NB)
      chemotherapy, which is severely neurotoxic. Acetyl-L-Carnitine (ALC) is a natural
      occurring compound with a neuroprotective activity in several experimental
      paradigms. The aim of this study was to determine the effects of ALC on cisplatin
      induced cytotoxicity and oxidative stress in NB cells. SH-SY5Y (N-Myc negative)
      and KELLY (N-Myc positive) human NB cell lines were used. Cisplatin induced
      apoptosis was assessed by using a Cell Death Detection ELISA(PLUS) kit. Lipid
      peroxidation levels were determined by HPLC analysis. Glutathione levels were
      determined spectrophotometrically. ALC was used prophylactic or after cisplatin
      application. The level of cisplatin doses were determined in both type of NB
      cells at which 50% cell death occurred along with synchronized apoptosis induced.
      Prophylactic 10 and 50 micromol of ALC concentrations were decreased cisplatin
      induced lipid peroxidation compared to controls that normally exhibited apoptosis
      especially in SH-SY5Y cells. Cisplatin caused oxidative stress through decreasing
      glutathione levels in both cell types. ALC were effectively inhibited the
      increase in cisplatin induced oxidized glutathione and lipid peroxidation
      formation in NB cells. We suggested that prophylactic ALC would be a useful agent
      for cisplatin induced toxicity in NB cells.

PMID- 19851865
TI  - D-beta-hydroxybutyrate prevents MPP+-induced neurotoxicity in PC12 cells.
AB  - Numerous studies show that D-beta-Hydroxybutyrate (DbetaHB) is neuroprotective.
      The present study was to explore the neuroprotective effects of DbetaHB against
      the cell death and apoptosis induced by 1-methyl-4-phenylpyridinium ion (MPP+) in
      PC12 cells. PC12 cells were pretreated with DbetaHB and followed by MPP+
      exposure. The cell viability was determined by MTT assay. The morphological
      characteristics of apoptosis was observed by Acridine Orange (AO) staining and
      apoptotic rates were measured by flow cytometer. The product of lipid
      peroxidation, malondialdehyde (MDA), was measured using thiobarbituric acid
      method. The mitochondrial membrane potential (MMP), intracellular ROS and total
      glutathione were detected by microplate reader. In PC12 cells, pretreatment with
      DbetaHB significantly reduced MPP+-induced the decrease of cell viability. AO
      staining and flow cytometric analysis found DbetaHB inhibited MPP+-induced
      apoptosis. The measurement of MDA formation showed that DbetaHB alleviated lipid
      peroxidation induced by MPP+. The loss of MMP induced by MPP+ was preventive by
      DbetaHB. The changes of intracellular ROS and total glutathione induced by MPP+
      were reversed by DbetaHB. DbetaHB protected PC12 cells against MPP+-induced death
      and apoptosis.

PMID- 19851867
TI  - Spatiotemporal changes of NGF, BDNF and NT-3 in the developing spinal cords of
      embryonic chicken.
AB  - Spatiotemporal changes of nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF) and neurotrophin-3 (NT-3) in the spinal cords of chick embryonic
      stage day 7 (E7) and day 14 (E14) were examined by using immunohistochemistry and
      Western blot. Intensive NGF immunoreaction (IR) was detected in the white matter
      of the spinal cords, while BDNF-IR in perikaryon and neurite, and NT-3-IR in the
      nucleus and cytoplasm were seen in the neurons of the ventral horn in the gray
      matter. Comparatively, the expressions for three growth factors have expanded
      largely into the dorsal horn at E14, and the level of proteins for these growth
      factors increased significantly in the spinal cords from E7 to E14. Morphological
      observation showed that the lumbar spinal cords of E7 appeared rectangular,
      whereas it gave a butterfly shape in the gray matter consisting of the typical
      ventral horn, dorsal horn and intermediate zone at E14. The present findings
      indicated that the spatiotemporal changes of NGF, BDNF and NT-3 could be
      associated to the morphological changes of developing spinal cords, suggesting
      the possible roles of three growth factors in the development of spinal cords.

PMID- 19851868
TI  - Systems analysis of the role of bone morphogenic protein 4 in endothelial
      inflammation.
AB  - Shear stress is an important factor in the onset and progression of
      atherosclerosis. High and unidirectional laminar stress is seen as protective,
      while low and oscillatory shear stress is considered pro-inflammatory and pro
      atherogenic. The mechanosensitive response of endothelial cells is governed by a
      complex system of genes, proteins, and signals that operate at distinctly
      different time scales. We propose a dynamic mathematical model that
      quantitatively describes this mechanosensing system and permits novel insights
      into its functioning. The model, the first of its kind, is constructed within the
      guidelines of Biochemical Systems Theory and accounts for different time scales
      by means of approximated delays. Parameter values are obtained directly from
      biochemical observations in an ad hoc fashion. The model reflects most documented
      observations well and leads to a number of predictions and novel hypotheses. In
      particular, it demonstrates the crucial role of Bone Morphogenic Protein 4 and
      p47(phox)-dependent NADPH oxidases in endothelial inflammation.

PMID- 19851869
TI  - The relationship between the content and the form of metaphorical statements.
AB  - Recent research suggests that the quality of a metaphorical topic-vehicle pairing
      should be the determinant to the choice of a proper grammatical form, nominal
      metaphor versus simile. Two studies examined the relationship between the quality
      of the content of a metaphorical statement and its grammatical form. Study 1
      showed that the two grammatical forms did not differ in aptness when the quality
      of topic-vehicle pairs and the conventionality of vehicles, a factor associated
      with the quality of metaphorical expressions, were controlled. With an online
      comprehension measure, Study 2 found that high quality metaphorical pairings were
      easier to process than low quality metaphorical pairings in both the metaphor
      form and the simile form. For high quality metaphorical pairings, information
      related to both the topics and the vehicles was highly activated at an early
      stage of processing. The relations among factors involved in the interpretive
      process of metaphorical language are discussed.

PMID- 19851870
TI  - Inhibiting TNF-mediated signaling: a novel therapeutic paradigm for androgen
      independent prostate cancer.
AB  - The tumor necrosis factor (TNF) receptor super family comprises of members that
      induce two distinct signaling cascades, leading to either cell survival or
      apoptosis. However, in prostate cancer (PCa), TNF-mediated prosurvival signaling
      is the predominant pathway that leads to cell survival and resistance to therapy.
      Although inhibition of TNF signaling by pharmacological agents or monoclonal
      antibodies has gained importance in the field of cancer therapy, toxicity to
      normal cells has impaired their extensive use for cancer treatment. We previously
      identified a natural, nontoxic compound psoralidin that inhibited viability and
      induced apoptosis in androgen independent prostate cancer (AIPC) cells. Thus, the
      goal of our study is to investigate whether psoralidin inhibits TNF-mediated
      prosurvival signaling in AIPC cells. Our results suggest that psoralidin inhibits
      constitutive and TNF-induced expression of TNF-alpha and its downstream
      prosurvival signaling molecules such as NF-kappaB and Bcl-2 in AIPC cells. On the
      other hand, psoralidin simultaneously induces the death receptor (DR)-mediated
      apoptotic signaling eventually causing the activation of caspase cascade and
      resultant induction of apoptosis. Oral administration of psoralidin inhibits
      expression of TNF-alpha and NF-kappaB/p65 in tumor sections, resulting in tumor
      regression in PC-3 xenografts. Our results suggest that psoralidin inhibits TNF
      mediated survival signaling in AIPC and thus is a potent therapeutic agent for
      prostate cancer.

PMID- 19851871
TI  - Cytochrome c-induced lymphocyte death from the outside in: inhibition by serum
      leucine-rich alpha-2-glycoprotein-1.
AB  - Previously we reported that serum leucine-rich alpha-2-glycoprotein-1 (LRG) binds
      cytochrome c (Cyt c; Cummings et al., Apoptosis 11:1121-1129, 2009). Here we show
      that LRG binding to Cyt c is similar to that of Apaf-1. LRG and Apaf-1 share
      partial amino acid sequences, compete for binding Cyt c, and are inhibited by
      modification at lysine 72 in Cyt c. However, in contrast to Apaf-1, LRG acts as a
      survival factor in vitro rather than a pro-apoptotic factor. By depleting LRG
      from culture medium we found that LRG protects against a toxic effect of
      exogenous Cyt c on lymphocytes that would otherwise result in an apoptotic
      phenotype. LRG, as well as antibodies specific for Cyt c, increased cell
      viability in the absence of added Cyt c indicating that Cyt c released by dying
      cells in the cultures is itself toxic. Protection from extracellular Cyt c
      induced lymphotoxicity appears to involve an active mechanism rather than steric
      hindrance of Cyt c. Thus, serum LRG when bound to extracellular Cyt c that is
      released from apoptotic cells acts as a survival factor for lymphocytes and
      possibly other cells that are susceptible to the toxic effect of extracellular
      Cyt c.

PMID- 19851872
TI  - Formation of biodegradable microcapsules utilizing 3D, selectively surface
      modified PDMS microfluidic devices.
AB  - We have successfully demonstrated the formation of biodegradable microcapsules
      utilizing PDMS double-emulsification devices. Specially designed 3D PDMS
      microchannels with surfaces selectively modified by a self-aligned photografting
      process are employed to generate monodisperse water-in-organic-solvent-in-water
      (W/O/W) emulsions in a controlled manner. Mainly by varying the outer and inner
      fluid flow-rates, the dimensions of resulting double emulsions can be adjusted as
      desired. Meanwhile, biodegradable materials are dissolved in the middle organic
      solvent (in this work ethyl acetate is used), and solidified into microcapsules
      once the solvent is extracted. In the prototype demonstration, microcapsules made
      up of poly(L-lactic acid), trilaurin, and phosphocholine were successfully
      fabricated. In addition, it was also demonstrated that gamma-Fe(2)O(3)
      nanoparticles can be simultaneously embedded into the microcapsules, which
      consequently become responsive to electromagnetic stimulation. As such, the
      presented PDMS microfluidic devices could potentially serve as versatile
      encapsulation apparatus, and the fabricated biodegradable microcapsules could
      function as controlled delivery systems, which are desired for a variety of
      biological and pharmaceutical applications.

PMID- 19851873
TI  - Pharmacokinetic and pharmacodynamic modeling of a monoclonal antibody antagonist
      of glucagon receptor in male ob/ob mice.
AB  - Elevated basal concentrations of glucagon and reduced postprandial glucagon
      suppression are partly responsible for the increased hepatic glucose production
      seen in type 2 diabetic patients. Recently, it was demonstrated that an
      antagonistic human monoclonal antibody (mAb) blocking glucagon receptor (GCGR)
      has profound glucose-lowering effects in various animal models. To further
      understand the effects on glucose homeostasis mediated by such an antibody, a
      pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in a diabetic ob/ob
      mouse model. Four groups of ob/ob mice were randomized to receive single
      intraperitoneal administration of placebo, 0.6, 1, or 3 mg/kg of mAb GCGR, a
      fully human mAb against GCGR. The concentration-time data were used for
      noncompartmental and compartmental analysis. A semi-mechanistic PK-PD model
      incorporating the glucose-glucagon inter-regulation and the hypothesized
      inhibitory effect of mAb GCGR on GCGR signaling pathway via competitive
      inhibition was included to describe the disposition of glucose and glucagon over
      time. The pharmacokinetics of mAb GCGR was well characterized by a two
      compartment model with parallel linear and nonlinear saturable eliminations.
      Single injection of mAb GCGR caused a rapid glucose-lowering effect with blood
      glucose concentrations returning to baseline by 4 to 18 days with increasing dose
      from 0.6 to 3 mg/kg. Elevation of glucagon concentrations was also observed in a
      dose-dependent manner. The results illustrated that the feedback relationship
      between glucose and glucagon in the presence of mAb GCGR could be quantitatively
      described by the developed model. The model may provide additional understanding
      in the underlying mechanism of GCGR antagonism by mAb.

PMID- 19851874
TI  - Genome-wide analysis of genes targeted by qLTG3-1 controlling low-temperature
      germinability in rice.
AB  - The control of seed germination under environmental conditions, where plants will
      be grown, is important for the adaptability of plants. Low-temperature is one of
      the most common environmental stress factors that affect plant growth and
      development and places a major limit on crop productivity in cultivated areas.
      Previously, qLTG3-1, a major quantitative trait locus controlling low-temperature
      tolerance at the germination stage in rice (called low-temperature germinability)
      was identified, which encodes a protein of unknown function. To identify genes
      targeted by qLTG3-1, a genome-wide expression profiling analysis using the 44 K
      Rice Oligo microarray was performed. Because the expression of qLTG3-1 was
      dramatically increased at 1 day after incubation, the expression profiles at this
      time were compared between Hayamasari, which has a loss-of-function qLTG3-1
      allele, and a near isogenic line with a functional allele. A total of 4,587 genes
      showed significant differences between their expression levels in the two lines.
      Most of these genes might be involved in the process of seed germination itself,
      and then a focus was made on qLTG3-1 dependently induced or suppressed genes,
      defined as 'qLTG3-1 dependent' genes. Twenty-nine 'qLTG3-1 dependent' genes with
      diverse functions were categorized, implying that disruption of cellular
      homeostasis leads to a wide range of metabolic alterations and diverse cross-talk
      between various signaling pathways. In particular, genes involved in defense
      responses were up-regulated by qLTG3-1, indicating that qLTG3-1 expression is
      required for the expression of defense response genes in low-temperature
      germinability in rice.

PMID- 19851875
TI  - Mhc class II diversity and balancing selection in greater prairie-chickens.
AB  - The major histocompatibility complex (Mhc) of domestic chickens has been
      characterized as small and relatively simple compared with that of mammals.
      However, there is growing evidence that the Mhc of many bird lineages may be more
      complex, even within the Order Galliformes. In this study, we measured genetic
      variation and balancing selection at Mhc loci in another galliform, the greater
      prairie-chicken. We cloned and sequenced a 239 bp fragment of Mhc Class II beta
      chain (BLB) exon 2 in 14 individuals. There was a total of 10 unique sequences
      and a minimum of four BLB loci. The d(N)/d(S) ratio at peptide-binding codons was
      significantly greater than one, suggesting balancing selection is acting on the
      BLB. We also recovered two YLB sequences, which clustered tightly with YLB
      sequences from three other species: domestic chicken, black grouse and common
      quail. The relatively large number of loci revealed in our study suggests that
      even closely related galliforms differ in the level of Mhc variation and
      structure.

PMID- 19851877
TI  - Intentional weight loss and risk of lymphohematopoietic cancers.
AB  - OBJECTIVES: We hypothesized that intentional weight loss may be associated with
      development of lymphohematopoietic cancers, based on observations of immune
      suppression following weight loss in short-term studies. METHODS: At the baseline
      of the Women's Health Initiative Observational Study (1994-1998), participants
      reported information about intentional weight loss episodes in the past 20 years.
      We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) among 81,219
      women for associations between past intentional weight loss and risk of
      developing non-Hodgkin lymphoma (NHL), leukemia, and multiple myeloma during an
      average 9.9 years of follow-up. RESULTS: The risk of NHL was associated with
      having lost a large maximum amount of weight (> or =50 pounds, HR = 1.68, 95% CI
      1.13-2.50). NHL risk also varied by the frequency of intentional weight loss;
      women had increased risk if they lost 50 pounds or more > or =3 times (HR = 1.97,
      95% CI 0.93-4.16; p trend by frequency = 0.09) or 20-49 pounds > or =3 times (HR
      = 1.55, 95% CI 1.00-2.40; p trend = 0.05), but there was no risk associated with
      smaller amounts of weight loss (10-19 pounds > or =3 times, HR = 0.78, 95% CI
      0.46-1.33). These associations persisted with adjustment for body mass index at
      different ages. We observed non-significant associations of similar magnitude for
      multiple myeloma, but past intentional weight loss episodes were not associated
      with leukemia. CONCLUSION: Further assessment of intentional weight loss as a
      possible risk factor for lymphomas may provide insight into the etiology of these
      cancers.

PMID- 19851876
TI  - Reproductive biology of Varroa destructor in Africanized honey bees (Apis
      mellifera).
AB  - Since its first contact with Apis mellifera, the population dynamics of the
      parasitic mite Varroa destructor varies from one region to another. In many
      regions of the world, apiculture has come to depend on the use of acaricides,
      because of the extensive damage caused by varroa to bee colonies. At present, the
      mite is considered to contribute to the recent decline of honey bee colonies in
      North America and Europe. Because in tropical climates worker brood rearing and
      varroa reproduction occurs all year round, it could be expected that here the
      impact of the parasite will be even more devastating. Yet, this has not been the
      case in tropical areas of South America. In Brazil, varroa was introduced more
      than 30 years ago and got established at low levels of infestation, without
      causing apparent damage to apiculture with Africanized honey bees (AHB). The
      tolerance of AHB to varroa is apparently attributable, at least in part, to
      resistance in the bees. The low fertility of this parasite in Africanized worker
      brood and the grooming and hygienic behavior of the bees are referred as
      important factors in keeping mite infestation low in the colonies. It has also
      been suggested that the type of mite influences the level of tolerance in a honey
      bee population. The Korea haplotype is predominant in unbalanced host-parasite
      systems, as exist in Europe, whereas in stable systems, as in Brazil, the Japan
      haplotype used to predominate. However, the patterns of varroa genetic variation
      have changed in Brazil. All recently sampled mites were of the Korea haplotype,
      regardless whether the mites had reproduced or not. The fertile mites on AHB in
      Brazil significantly increased from 56% in the 1980s to 86% in recent years.
      Nevertheless, despite the increased fertility, no increase in mite infestation
      rates in the colonies has been detected so far. A comprehensive literature review
      of varroa reproduction data, focusing on fertility and production of viable
      female mites, was conducted to provide insight into the Africanized bee host
      parasite relationship.

PMID- 19851878
TI  - Identification of heavy metal sources by multivariable analysis in a typical
      Mediterranean city (SE Spain).
AB  - Problems associated with heavy metal characterization in the majority of sites
      are often due to multiple sources of pollution. This work presents the results
      through the use of advanced statistical techniques to identify sources of soil
      heavy metals in a typical Mediterranean city. The multivariable analysis
      performed on seven metals identified four sources controlling their variability.
      Cr, Mn, and Ni contents were associated to soil parent materials; Cd and Pb
      contents were related to anthropogenic activities, specifically industrial
      activities and traffic; Cu content is controlled by long-term application of
      inorganic fertilizers in agricultural areas. Finally, zinc concentration is
      associated to commercial and outdoor activities in the area. These results were
      supported by the fact that metals associated to parent material (Cr, Mn, and Ni)
      were better correlated with soil lithogenic properties, while anthropogenic
      metals were correlated with more variable soil constituents.

PMID- 19851879
TI  - Preface.

PMID- 19851880
TI  - Associations among milk production traits and glycosylated haemoglobin in dairy
      cattle; importance of lactose synthesis potential.
AB  - Glucose is the major precursor of lactose synthesis in the mammary gland. Lactose
      the major carbohydrate and osmolyte of milk, controls milk volume and its
      concentration. Glycosylated haemoglobin (HbG) is a retrospective measure of mean
      blood glucose level and it is largely unaffected by recent physiological
      conditions and environmental events. The purposes of this study were to determine
      the correlations between lactose traits and other milk production traits in dairy
      cattle and to investigate whether HbG level can be correlated with milk and
      lactose production traits. Here, HbG percentage, milk and lactose production
      traits including milk yield, lactose, protein, SNF, total solid and fat
      percentages and yields were measured in 485 second calved Iranian Holstein
      cattle. Statistically significant negative correlations were established between
      HbG and milk yield (r = -0.88), lactose yield (r = -0.83), SNF yield (r = -0.81),
      protein yield (r = -0.79) and total solid yield (r = -0.74). Positive
      correlations were established between lactose yield and milk (r = 0.96), protein
      (r = 0.81), SNF (r = 0.92) and total solid (r = 0.79) yields. The negative
      correlation between HbG and milk and total lactose production is probably related
      to the higher glucose demands in the lactating mammary gland of more productive
      cows. The positive correlation between lactose yield and milk, protein, SNF and
      total solid yield indicates that the level of lactose synthesis influences milk
      production traits in ways other than merely via its osmolytic action.

PMID- 19851881
TI  - Arabidopsis thaliana Rubisco small subunit transit peptide increases the
      accumulation of Thermotoga maritima endoglucanase Cel5A in chloroplasts of
      transgenic tobacco plants.
AB  - Over the past decade various approaches have been used to increase the expression
      level of recombinant proteins in plants. One successful approach has been to
      target proteins to specific subcellular sites/compartments of plant cells, such
      as the chloroplast. In the study reported here, hyperthermostable endoglucanase
      Cel5A was targeted into the chloroplasts of tobacco plants via the N-terminal
      transit peptide of nuclear-encoded plastid proteins. The expression levels of
      Cel5A transgenic lines were then determined using three distinct transit
      peptides, namely, the light-harvesting chlorophyll a/b-binding protein (CAB),
      Rubisco small subunit (RS), and Rubisco activase (RA). RS:Cel5A transgenic lines
      produced highly stable active enzymes, and the protein accumulation of these
      transgenic lines was up to 5.2% of the total soluble protein in the crude leaf
      extract, remaining stable throughout the life cycle of the tobacco plant.
      Transmission election microscopy analysis showed that efficient targeting of
      Cel5A protein was under the control of the transit peptide.

PMID- 19851882
TI  - Intracranial artery calcification in hemodialysis patients.
AB  - Intracranial artery calcification is an independent risk factor for ischemic
      stroke, and while it is frequently observed on computed tomographic images of the
      brain in hemodialysis patients, its distribution has not been well studied. Fifty
      patients on maintenance hemodialysis were enrolled in this study. We divided the
      patients with intracranial artery calcification into two groups according to the
      duration of maintenance hemodialysis and compared the frequency of intracranial
      calcification of each of the intracranial arteries between the two groups.
      Intracranial artery calcification was found in 36 of the 50 hemodialysis
      patients. Among the 36 patients with intracranial artery calcification, the
      prevalence of calcification of each of the arteries was as follows: vertebral
      artery, 58.3%; internal carotid artery, 61.1%; basilar artery, 41.7%; anterior
      cerebral artery, 16.7%; middle cerebral artery, 30.6%; posterior cerebral artery,
      8.3%. The prevalence of calcification of each of the intracranial arteries did
      not differ significantly between the patients with a hemodialysis duration of
      more than 20 years and those less than 20 years. The most frequently involved
      site of calcification was the internal carotid artery. The prevalence of
      calcification of the other intracranial arteries, particularly of the basilar
      artery, were relatively high. The prevalence of calcification of each of the
      intracranial arteries did not differ significantly between the patients with a
      hemodialysis duration of more than 20 years and less than 20 years.

PMID- 19851884
TI  - Relation of plaque size to compositions as determined by an in vivo volumetric
      intravascular ultrasound radiofrequency analysis.
AB  - As the plaques have enlarged, the changes in specific plaque compositions have
      not been sufficiently investigated. We evaluated the relation of plaque size to
      each plaque component (fibrotic, fibrofatty, dense calcium, and necrotic core) in
      244 patients with volumetric virtual histology intravascular ultrasound analysis.
      Plaque volume was significantly correlated with fibrotic volume (r = 0.886, P <
      0.001), necrotic core volume (r = 0.716, P < 0.001), fibrofatty volume (r =
      0.572, P < 0.001), and dense calcium volume (r = 0.382, P < 0.001). There was a
      weak correlation between plaque volume and percentage of fibrofatty plaque and
      dense calcium (r = 0.140, P = 0.030 and r = -0.146, P = 0.023, respectively).
      Plaque volume was not significantly correlated with percentage of fibrotic plaque
      and necrotic core. As the plaque volume increased, there was an increase in
      absolute amounts of each plaque component (fibrotic > necrotic core > fibrofatty
      > dense calcium). However, there were no significantly relevant correlations
      between plaque volume and percentage of each plaque component.

PMID- 19851885
TI  - Examination of potential virulence factors of Candida tropicalis clinical
      isolates from hospitalized patients.
AB  - Candida tropicalis has been reported to be one of the Candida species which is
      most likely to cause bloodstream and urinary tract infections in hospitalized
      patients. Accordingly, the aim of this study was to characterize the virulence of
      C. tropicalis by assessing antifungal susceptibility and comparing the expression
      of several virulence factors. This study was conducted with seven isolates of C.
      tropicalis from urine and blood cultures and from central venous catheter. C.
      tropicalis ATCC 750 was used as reference strain. Yeasts adhered (2 h) to
      epithelial cells and silicone and 24 h biofilm biomass were determined by crystal
      violet staining. Pseudohyphae formation ability was determined after growth in
      fetal bovine serum. Enzymes production (hemolysins, proteases, phospholipases)
      was assessed by halo formation on agar plates. Susceptibility to antifungal
      agents was determined by E-test. Regarding adhesion, it can be highlighted that
      C. tropicalis strains adhered significantly more to epithelium than to silicone.
      Furthermore, all C. tropicalis strains were able to form biofilms and to express
      total hemolytic activity. However, protease was only produced by two isolates
      from urine and by the isolates from catheter and blood. Moreover, only one C.
      tropicalis (from catheter) was phospholipase positive. All isolates were
      susceptible to voriconazole, fluconazole and amphotericin B. Four strains were
      susceptible-dose dependent to itraconazole and one clinical isolate was found to
      be resistant.

PMID- 19851883
TI  - Optical microscopy in photosynthesis.
AB  - Emerging as well as the most frequently used optical microscopy techniques are
      reviewed and image contrast generation methods in a microscope are presented,
      focusing on the nonlinear contrasts such as harmonic generation and multiphoton
      excitation fluorescence. Nonlinear microscopy presents numerous advantages over
      linear microscopy techniques including improved deep tissue imaging, optical
      sectioning, and imaging of live unstained samples. Nonetheless, with the
      exception of multiphoton excitation fluorescence, nonlinear microscopy is in its
      infancy, lacking protocols, users and applications; hence, this review focuses on
      the potential of nonlinear microscopy for studying photosynthetic organisms.
      Examples of nonlinear microscopic imaging are presented including isolated light
      harvesting antenna complexes from higher plants, starch granules, chloroplasts,
      unicellular alga Chlamydomonas reinhardtii, and cyanobacteria Leptolyngbya sp.
      and Anabaena sp. While focusing on nonlinear microscopy techniques, second and
      third harmonic generation and multiphoton excitation fluorescence microscopy,
      other emerging nonlinear imaging modalities are described and several linear
      optical microscopy techniques are reviewed in order to clearly describe their
      capabilities and to highlight the advantages of nonlinear microscopy.

PMID- 19851886
TI  - CK2 phosphorylates TNFAIP1 to affect its subcellular localization and interaction
      with PCNA.
AB  - TNFAIP1 is a protein which can be induced by tumor necrosis factoralpha
      (TNFalpha) and interleukin-6 (IL-6), it may play roles in DNA synthesis, DNA
      repair, cell apoptosis and human diseases. However, very little has been known
      about how TNFAIP1 acts in these physiological processes. In this paper, CK2beta
      was identified as a partner of TNFAIP1 by screening the HeLa cDNA library in
      yeast two-hybrid system with TNFAIP1 as a bait. Furthermore, it was demonstrated
      that CK2 could phosphorylate TNFAIP1 in vitro and in vivo, which facilitated the
      distribution of TNFAIP1 in nucleus and enhanced its interaction with PCNA. It is
      suggested that the phosphorylation of TNFAIP1 may be required for its functions.

PMID- 19851888
TI  - Complex governance to cope with global environmental risk: an assessment of the
      United Nations Framework Convention on Climate Change.
AB  - In this article, a framework is suggested to deal with the analysis of global
      environmental risk governance. Climate Change is taken as a particular form of
      contemporary environmental risk, and mobilised to refine and characterize some
      salient aspects of new governance challenges. A governance framework is
      elaborated along three basic features: (1) a close relationship with science, (2)
      an in-built reflexivity, and (3) forms of governmentality. The UNFCCC-centered
      system is then assessed according to this three-tier framework. While the two
      first requisites are largely met, the analysis of governmentality points to some
      institutional weak spots.

PMID- 19851887
TI  - An Ashkenazi founder mutation in the MSH6 gene leading to HNPCC.
AB  - Mutations in DNA mismatch repair genes underlie lynch syndrome (HNPCC). Lynch
      syndrome resulting from mutations in MSH6 is considered to be attenuated in
      comparison to that caused by mutations in MLH1 and MSH2, thus more likely to be
      under diagnosed. In this study we report of a common mutation in the MSH6 gene in
      Ashkenazi Jews. Genetic counseling and diagnostic work-up for HNPCC was conducted
      in families who attended the high risk clinic for inherited cancer. We identified
      the mutation c.3984_3987dup in the MSH6 gene in 19 members of four unrelated
      Ashkenazi families. This mutation results in truncation of the transcript and in
      loss of expression of the MSH6 protein in tumors. Tumor spectrum among carriers
      included colon, endometrial, gastric, ovarian, urinary, and breast cancer. All
      but one family qualified for the Bethesda guidelines and none fulfilled the
      Amsterdam Criteria. Members of one family also co-inherited the c.6174delT
      mutation in the BRCA2 gene. The c.3984_3987dup in the MSH6 gene is a mutation
      leading to HNPCC among Ashkenazi Jews. This is most probably a founder mutation.
      In contrast to the c.1906G>C founder mutation in the MSH2 gene, tumors tend to
      occur later in life, and none of the families qualified for the Amsterdam
      criteria. c.3984_3987dup is responsible for 1/6 of the mutations identified among
      Ashkenazi HNPCC families in our cohort. Both mutations: c.3984_3987dup and
      c.1906G>C account for 61% of HNPCC Ashkenazi families in this cohort. These
      findings are of great importance for counseling, diagnosis, management and
      surveillance for Ashkenazi families with Lynch syndrome.

PMID- 19851889
TI  - (1)H, (15)N, and (13)C chemical shift assignments of neuronal calcium sensor-1
      homolog from fission yeast.
AB  - The neuronal calcium sensor (NCS) proteins regulate signal transduction processes
      and are highly conserved from yeast to humans. We report complete NMR chemical
      shift assignments of the NCS homolog from fission yeast (Schizosaccharomyces
      pombe), referred to in this study as Ncs1p. (BMRB no. 16446).

PMID- 19851890
TI  - Activation of p38 MAPK pathway by hepatitis C virus E2 in cells transiently
      expressing DC-SIGN.
AB  - Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin
      (DC-SIGN) is a cellular receptor for hepatitis C virus for the binding of viral
      envelope glycoprotein E2. Interaction of DC-SIGN with the E2 may evoke cellular
      signal transduction implicated in viral pathogenesis. We developed a cell model
      with DC-SIGN transient transfection to study p38 mitogen-activated protein kinase
      (MAPK) signaling pathway in response to the E2 treatment. HEK293T and HeLa were
      DC-SIGN-deficient cell lines. DC-SIGN was detectable at the surface of HEK293T
      and HeLa transfected with DC-SIGN, and the levels of DC-SIGN were high in
      transfected-HEK293T as compared with HeLa. The transfected-HEK293T displayed
      ability for the E2 binding. In the transfected-HEK293T, level of p38 MAPK
      phosphorylation was increased upon the E2 treatment and reduced following
      blockage of DC-SIGN with an antibody against DC-SIGN. Phosphorylation of
      downstream transcription factor activating transcription factor (ATF)-2 was also
      up-regulated by the E2 via DC-SIGN. Similar results were obtained with NIH3T3
      cells stably expressing DC-SIGN and Huh7 cells. Our results indicate that DC-SIGN
      transient expression in HEK293T is a useful cell model for investigating p38 MAPK
      pathway triggered by the E2, which may provide information for understanding
      cellular receptors-mediated signaling events and the viral pathogenesis.

PMID- 19851891
TI  - The influence of 1800 MHz GSM-like signals on hepatic oxidative DNA and lipid
      damage in nonpregnant, pregnant, and newly born rabbits.
AB  - The aim of our study is to evaluate the possible biological effects of whole-body
      1800 MHz GSM-like radiofrequency (RF) radiation exposure on liver oxidative DNA
      damage and lipid peroxidation levels in nonpregnant, pregnant New Zealand White
      rabbits, and in their newly borns. Eighteen nonpregnant and pregnant rabbits were
      used and randomly divided into four groups which were composed of nine rabbits:
      (i) Group I (nonpregnant control), (ii) Group II (nonpregnant-RF exposed), (iii)
      Group III (pregnant control), (iv) Group IV (pregnant-RF exposed). Newborns of
      the pregnant rabbits were also divided into two groups: (v) Group V (newborns of
      Group III) and (vi) Group VI (newborns of Group III). 1800 MHz GSM-like RF
      radiation whole-body exposure (15 min/day for a week) was applied to Group II and
      Group IV. No significant differences were found in liver 8 OHdG/10(6) dG levels
      of exposure groups (Group II and Group IV) compared to controls (Group I and
      Group III). However, in Group II and Group IV malondialdehyde (MDA) and ferrous
      oxidation in xylenol orange (FOX) levels were increased compared to Group I (P <
      0.05, Mann-Whitney). No significant differences were found in liver tissue of 8
      OHdG/10(6) dG and MDA levels between Group VI and Group V (P > 0.05, Mann
      Whitney) while liver FOX levels were found significantly increased in Group VI
      with respect to Group V (P < 0.05, Mann-Whitney). Consequently, the whole-body
      1800 MHz GSM-like RF radiation exposure may lead to oxidative destruction as
      being indicators of subsequent reactions that occur to form oxygen toxicity in
      tissues.

PMID- 19851892
TI  - How I treat patients with EEG patterns on the ictal-interictal continuum in the
      neuro ICU.
AB  - Refractory status epilepticus (RSE) is associated with a high risk of poor
      outcome and treated by most neurointensivists with continuous intravenous
      antiepileptic medications (cIV-AEDs). Continuous EEG monitoring has allowed us to
      unveil a number of epileptiform patterns of less certain significance. These have
      been labeled ictal to interictal continuum (IIC), many of which are associated
      with poor outcome. It is unclear to which extent individual patterns are
      epiphenomena or lead to additional brain injury. The treatment of these patterns
      is highly controversial and guidelines how to manage them are non existent. In
      this review of a challenging case, I will discuss a number of approaches to
      determine the ictal nature of the IIC in an effort to minimize neuronal injury
      from epileptiform brain activity on the one hand and from the treatment on the
      other hand. Ultimately it will be most important to replace the dichotomy of
      ictal versus non-ictal patterns by differentiating between harmful and non
      harmful patterns.

PMID- 19851894
TI  - Erythrocyte osmotic fragility and lipid peroxidation in experimental
      hyperthyroidism.
AB  - This study investigated the relation between erythrocyte osmotic fragility and
      oxidative stress and antioxidant state in primary hyperthyroidism induced
      experimental rats. Twenty-four Spraque-Dawley-type female rats weighing between
      160 and 200 g were divided into two, as control (n = 10) and experimental (n =
      12), groups. The experimental group animals have received tap water and L
      Tiroksin (0.4 mg/100 g fodder) added standard fodder for 30 days to induce
      hyperthyroidism. Control group animals were fed tap water and standard fodder for
      the same period. Blood samples were drawn from the abdominal aorta of the rats
      under ether anesthesia. T3, T4, and TSH levels, osmotic fragility,
      malondialdehyde (MDA), superoxide dismutase, and glutathione levels were measured
      in the blood. There was a statistically significant deviation found in maximum
      and minimum osmotic hemolysis limit values of experimental group when compared to
      controls. The standard hemolytic increment curve of the hyperthyroid group
      shifted to the right when compared to control group's curve. There was a
      statistically significant increase found in MDA and superoxide dismutase, but
      statistically a significant decrease was detected in glutathione levels in
      hyperthyroid group when compared to controls. As a result of our study, it may be
      concluded that hyperthyroidism may led to an increase in osmotic fragility of
      erythrocytes and this situation may possibly originate from the increased lipid
      peroxidation in hyperthyroidism.

PMID- 19851893
TI  - Identification of european allergy patterns to the allergen families PR-10, LTP,
      and profilin from Rosaceae fruits.
AB  - High fruit intakes are associated with significant health benefits but fruit
      allergy sufferers may be discouraged from eating fruit due to the symptoms they
      experience. Knowledge about allergens involved in fruit allergy and the frequent
      cross-reactions to other allergens is essential to (a) design the best strategy
      for fruit allergy testing (b) prescribe optimal avoidance diets, and (c) design
      technological solutions for development of hypoallergenic fruits. The objective
      of this review was to investigate whether some characteristic disease entities
      could be identified in Europe for allergy to Rosaceae fruits. Five allergy
      patterns were found involving the allergen families PR-10, LTP, and profilin. In
      the Western Mediterranean area allergies to Rosaceae fruits are caused by
      monosensitization to LTP, monosensitization to profilin, or co-sensitization to
      both these allergens. On the contrary, monosensitization to PR-10 and, to a
      lesser degree, co-sensitization to profilin and PR-10 is dominant in Northern and
      Central Europe. LTP sensitization is present both in pollinosis and non
      pollinosis patients and is associated with peach allergy in particular. The
      disease pattern for patients sensitized to profilin is characterized by several
      concomitant allergies including grass and other pollens, Rosaceae and non
      Rosaceae fruits. Finally, PR-10 sensitization is primarily associated to
      concomitant birch pollen and apple allergy.

PMID- 19851895
TI  - Clinicopathological analysis of primary epithelial appendiceal neoplasms.
AB  - Appendiceal carcinomas are classified into three distinct histopathological
      disease entities: disseminated peritoneal adenomucinosis (DPAM), peritoneal
      mucinous carcinomatosis (PMCA), or peritoneal mucinous carcinomatosis with
      intermediate or discorant features (PMCA I/D). The treatment of appendiceal
      tumors should be based on accurate histopathological classification, per
      previously reported case series. The objective of this study was to evaluate the
      clinicopathologic presentation and outcome of patients with appendiceal tumors
      treated at our institution over a 15-year period. We identified patients with
      appendiceal tumors diagnosed or treated at our institution from January 1989
      through May 2004. Chart review for age, gender, signs and symptoms at diagnosis,
      and treatment was performed. Review of the pathologic specimens was performed and
      tumors were classified as DPAM, PMCA I/D, or PMCA. Forty patients were identified
      (median age 52.5 years; males 38%). The number of patients with DPAM, PMCA I/D,
      and PMCA was 15 (38%), 6 (15%), and 18 (46%), respectively. Peritoneal
      involvement was seen in 11 (73%) of patients with DPAM, 5 (83%) of PMCA I/D, and
      11 (61%) of PMCA. The median survival for patients with DPAM, PMCA I/D, and PMCA
      was 7.7 years (90% CI: 2.9--upper limit not estimable), 1.2 years (90% CI: 0.9
      1.6), and 0.7 years (90% CI: 0.4-1.5), respectively. The difference in survival
      across the three groups was statistically significant. Three distinct
      histopathological disease entities exist in appendiceal tumors. The prognosis and
      management of these tumors should be based on the extent of disease and
      pathologic diagnosis.

PMID- 19851896
TI  - Using accumulated degree-days to estimate postmortem interval from the DNA yield
      of porcine skeletal muscle.
AB  - Determining the age of meat may require DNA extraction from tissue that may be
      frozen, chilled or sold over the counter of butchers. Until now, there has no
      systematic study on the ageing of meat. In the human application, the parallel is
      the determination of the time of death or postmortem interval (PMI). The purpose
      of this study was to investigate the effect of accumulated degree-days on the DNA
      yield of skeletal muscle and its possible application to estimate PMI. This study
      focused on the exposure of skeletal muscle tissue to a coastal environment. Two
      specimens of Sus domesticus, each weighing approximately 45 kg, were placed above
      ground to decompose over time. One pig was sampled over the summer season
      (December to February) and the other specimen during the winter season (June to
      August). Both the summer and winter pig studies were conducted in Drummond Cove,
      on the Mid West coast of Western Australia. Samples of muscle were collected at 2
      day intervals for the summer and winter pigs. The daily maximum and minimum
      environmental temperature and humidity was recorded. Although time is an
      important factor in the degradation of DNA it is not critical. This study
      confirms that DNA degradation is best modelled as dependent on accumulated
      temperature rather than just time. The sequential nature and an initial decrease
      in the DNA yield in skeletal muscle has the potential to apply to estimation of
      PMI but further tests need to be conducted to confirm our findings.

PMID- 19851897
TI  - Retinal hemorrhages associated with meningitis in a child with a congenital
      disorder of glycosylation.
AB  - A 9-month old infant presented in a state of shock to a district hospital. She
      was subsequently referred to the regional tertiary hospital. On admission,
      bruises were noted on the vertex of the skull. Retinal hemorrhages were present
      on ophthalmological examination. CT scan of the brain showed poor grey-white
      matter differentiation with apparent frontoparietal fractures of the skull. Her
      case was subsequently referred to the relevant authorities as it was suspicious
      for nonaccident injury (NAI). Her condition deteriorated and she died the next
      day. Postmortem examination showed that the bruises on the vertex were caused by
      rapid widening of the sutures of the skull, caused by rising intracranial
      pressure. There was no skull fracture or evidence of trauma. Histological
      examination of the brain showed meningitis which had extended to the optic nerve
      sheath. Hemorrhages were noted in the retinas as well as the optic nerve sheath.
      An incidental congenital disorder of glycosylation (CDG) was diagnosed on brain
      histology and confirmed by metabolic tests. Retinal hemorrhages are known to
      occur in head injuries especially in association with NAI. In this case,
      suspicion of NAI was further augmented by the presence of apparent bruises on the
      head. The full postmortem examination showed no evidence of injuries and instead
      showed that the child was suffering from meningitis. Blood culture grew Group A
      Streptococcus pyogenes. The underlying mechanisms for such a presentation and the
      association with CDG are discussed.

PMID- 19851898
TI  - Age differences in output-monitoring accuracy.
AB  - Output monitoring refers to memory for whether an intended action has been
      completed. Failures in output monitoring can lead to action repetitions or action
      omissions. Output monitoring is difficult for both younger and older adults, but
      few studies have examined age differences in output monitoring. Two experiments
      using a picture-based prospective memory task with an output-monitoring component
      were conducted to investigate the role of increased contextual detail and pre
      exposure on output-monitoring accuracy in younger and older adults. Across the
      two experimental manipulations older adults demonstrated less accurate output
      monitoring by primarily committing errors of repetition. Pre-exposure to targets
      resulted in worse output-monitoring accuracy for both younger and older adults.

PMID- 19851899
TI  - Self-reported cognitive inconsistency in older adults.
AB  - Insight into one's own cognitive abilities, or metacognition, has been widely
      studied in developmental psychology. Relevance to the clinician is high, as
      memory complaints in older adults show an association with impending dementia,
      even after controlling for likely confounds. Another candidate marker of
      impending dementia under study is inconsistency in cognitive performance over
      short time intervals. Although there has been a recent proliferation of studies
      of cognitive inconsistency in older adults, to date, no one has examined adults'
      self-perceptions of cognitive inconsistency. Ninety-four community-dwelling older
      adults (aged 70-91) were randomly selected from a parent longitudinal study of
      short-term inconsistency and long-term cognitive change in aging. Participants
      completed a novel 40-item self-report measure of everyday cognitive
      inconsistency, including parallel scales indexing perceived inconsistency 5 years
      ago and at present, yielding measures of past, present, and 5-year change in
      inconsistency. The questionnaire showed acceptable psychometric characteristics.
      The sample reported an increase in perceived inconsistency over time. Higher
      reported present inconsistency and greater 5-year increase in inconsistency were
      associated with noncognitive (e.g., older age, poorer ADLs, poorer health, higher
      depression), metacognitive (e.g., poorer self-rated memory) and
      neuropsychological (e.g., poorer performance and greater 5-year decline in global
      cognitive status, vocabulary, and memory) measures. Correlations between self
      reported inconsistency and neuropsychological performance were attenuated, but
      largely persisted when self-rated memory and age were controlled. Observed
      relationships between self-reported inconsistency and measures of
      neuropsychological (including memory) status and decline suggest that self
      perceived inconsistency may be an area of relevance in evaluating older adults
      for memory disorders.

PMID- 19851901
TI  - '1966 and all that': Trends and developments in UK ergonomics during the 1960s.
AB  - The 1960s represents a key decade in the expansion of ergonomics within the UK.
      This paper reviews trends and developments that emerged out of the 1960s and
      compares these with ergonomics research and practice today. The focus in
      particular is on the expansion of ergonomics as a discipline within industry, as
      well as more specific topics, such as the emergence of areas of interest, for
      example, computers and technology, automation and systems ergonomics and consumer
      ergonomics. The account is illustrated with a detailed timeline of developments,
      a set of industrial case studies and the contents of important publications
      during the decade. A key aim of the paper is to provide the opportunity to
      reflect on the past and the implications this may have for future directions for
      ergonomics within the UK. The paper provides practitioners with an insight into
      the development of ergonomics in the UK during one of the most important decades
      of its history. This is especially relevant given the fact that in 2009 the
      Ergonomics Society celebrates its 60th anniversary.

PMID- 19851902
TI  - Influence of 2D and 3D view on performance and time estimation in minimal
      invasive surgery.
AB  - This study aimed to evaluate the impact of two-dimensional (2D) and three
      dimensional (3D) images on time performance and time estimation during a surgical
      motor task. A total of 60 subjects without any surgical experience (nurses) and
      20 expert surgeons performed a fine surgical task with a new laparoscopic
      technology (da Vinci robotic system). The 80 subjects were divided into two
      groups, one using 3D view option and the other using 2D view option. We measured
      time performance and asked subjects to verbally estimate their time performance.
      Our results showed faster performance in 3D than in 2D view for novice subjects
      while the performance in 2D and 3D was similar in the expert group. We obtained a
      significant interaction between time performance and time evaluation: in 2D
      condition, all subjects accurately estimated their time performance while they
      overestimated it in the 3D condition. Our results emphasise the role of 3D in
      improving performance and the contradictory feeling about time evaluation in 2D
      and 3D. This finding is discussed in regard with the retrospective paradigm and
      suggests that 2D and 3D images are differently processed and memorised.

PMID- 19851903
TI  - The influence of laboratory set-up in usability tests: effects on user
      performance, subjective ratings and physiological measures.
AB  - This article examines the influences of situational factors on user behaviour in
      usability tests. Sixty participants carried out two tasks on a computer-simulated
      prototype of a mobile phone. Employing a 3 x 2 mixed experimental design,
      laboratory set-up was varied as a between-subjects variable (presence of
      facilitator and two non-interactive observers, presence of facilitator or no
      person present) while task difficulty was manipulated as a within-subjects
      variable (low vs. high). Performance data, subjective measures and physiological
      parameters (e.g. heart rate variability) were taken. The results showed that the
      presence of non-interactive observers during a usability test led to a
      physiological stress response, decreased performance on some measures and
      affected the emotional state of test participants. The presence of a facilitator
      (i.e. a participating observer) also influenced the emotional state of the test
      participant. Practitioners involved in usability testing need to be aware of
      undue influences of observers, in particular, if the observers are non
      interactive. The findings presented in this paper have implications for the
      practice of usability testing. They indicated a considerable influence of
      observers on test participants (physiology and emotions) and on the outcomes of
      usability tests (performance measures). This should be considered when selecting
      the set-up of a usability testing procedure.

PMID- 19851904
TI  - Hand dominance and hand use behaviour reported in a survey of 2437 Koreans.
AB  - Most tools, utensils, office equipment, home appliances, clothes, medical
      instruments, sporting goods, weapons and public facilities are made for people
      who are right-handed. Many left-handed people have to endure a certain amount of
      inconvenience or difficulty in carrying out daily activities in such an
      environment. In this study, 2437 Korean male and female participants were
      randomly selected to collect a variety of data on hand dominance and hand
      preference when handling diverse products and facilities. Their responses in a
      questionnaire survey revealed that 5.8% were left-handed and 7.9% were
      ambidextrous. The younger participants who were from teens to 39 years reported
      higher percentages of left-handedness than those over 40 years, with those in
      their thirties reporting the highest proportion of left-handedness (7.3-7.6%) for
      both men and women. A slightly higher percentage of the male participants (5.9%)
      said that they were left-handed than did the female participants (5.6%). However,
      the percentage who were ambidextrous varied with age group, but overall there was
      a higher percentage of women (8.3%) than of men (7.6%). The analysis of hand use
      behaviour revealed that the right-handed and ambidextrous people had a tendency
      to use their right hands more for actions that required accuracy than those that
      required force. The left-handed people had a strong tendency to use their left
      hands more often when making a forceful action than for one that required
      accuracy. Derived from these results, the conclusion is that, depending on their
      hand dominance, people seem to use their hands differently when they handle
      objects or use facilities, which should be considered in the design of hand
      controlled devices. Depending on which hand is the dominant one, people seem to
      use their hands differently when they handle objects or use facilities. The left
      handed tend to use their left hands more with force-required motions than with
      accuracy-required motions, while ambidextrous and right-handed people use their
      right hands more with accuracy-required motions than with force-required motions.
      Designers of products and facilities will find the results of this study useful
      for developing hand-controlled devices and systems.

PMID- 19851905
TI  - Task factor usability ratings for different age groups writing Chinese.
AB  - This study evaluated how different task factors affect performance and user
      subjective preferences for three different age groups of Chinese subjects (6-11,
      20-23, 65-70 years) when hand writing Chinese characters. The subjects copied
      Chinese character sentences with different settings for the task factors of
      writing plane angle (horizontal 0 degrees , slanted 15 degrees ), writing
      direction (horizontal, vertical), and line spacing (5 mm, 7 mm and no lines).
      Writing speed was measured and subjective preferences (effectiveness and
      satisfaction) were assessed for each of the task factor settings. The result
      showed that there was a conflict between writing speed and personal preference
      for the line spacing factor; 5 mm line spacing increased writing speed but it was
      the least preferred. It was also found that: vertical and horizontal writing
      directions and a slanted work surface suited school-aged children; a horizontal
      work surface and horizontal writing direction suited university students; and a
      horizontal writing direction with either a horizontal or slanted work surface
      suited the older adults.

PMID- 19851906
TI  - Principles for the wise use of computers by children.
AB  - Computer use by children at home and school is now common in many countries.
      Child computer exposure varies with the type of computer technology available and
      the child's age, gender and social group. This paper reviews the current exposure
      data and the evidence for positive and negative effects of computer use by
      children. Potential positive effects of computer use by children include enhanced
      cognitive development and school achievement, reduced barriers to social
      interaction, enhanced fine motor skills and visual processing and effective
      rehabilitation. Potential negative effects include threats to child safety,
      inappropriate content, exposure to violence, bullying, Internet 'addiction',
      displacement of moderate/vigorous physical activity, exposure to junk food
      advertising, sleep displacement, vision problems and musculoskeletal problems.
      The case for child specific evidence-based guidelines for wise use of computers
      is presented based on children using computers differently to adults, being
      physically, cognitively and socially different to adults, being in a state of
      change and development and the potential to impact on later adult risk. Progress
      towards child-specific guidelines is reported. Finally, a set of guideline
      principles is presented as the basis for more detailed guidelines on the
      physical, cognitive and social impact of computer use by children. The principles
      cover computer literacy, technology safety, child safety and privacy and
      appropriate social, cognitive and physical development. The majority of children
      in affluent communities now have substantial exposure to computers. This is
      likely to have significant effects on child physical, cognitive and social
      development. Ergonomics can provide and promote guidelines for wise use of
      computers by children and by doing so promote the positive effects and reduce the
      negative effects of computer-child, and subsequent computer-adult, interaction.

PMID- 19851907
TI  - Studying the relationship between low back pain and working postures among those
      who stand and those who sit most of the working day.
AB  - A relationship between low back pain (LBP) and prolonged standing or prolonged
      sitting at work has not been clearly shown, despite its biological plausibility.
      Because sitting and standing postures vary as to duration and freedom to
      alternate postures, and standing postures vary as to mobility, associations
      between specific working postures and LBP were explored using multiple logistic
      regression. Associations between work factors and self-reported LBP during the
      previous 12 months that interfered with usual activities were examined among 4493
      standing workers and 3237 sitting workers interviewed in the 1998 Quebec Health
      and Social Survey; 24.5% reported significant LBP. Since the same conditions can
      correspond to different physiological demands for sitting compared with standing
      workers, analyses were performed separately for the two groups. Standing without
      freedom to sit was associated with LBP. Different occupational physical and
      psychosocial factors were associated with LBP in sitting compared with standing
      populations.

PMID- 19851908
TI  - The impact of ergonomic work environment exposures on the risk of disability
      pension: Prospective results from DWECS/DREAM.
AB  - The objectives were to identify the impact of ergonomic work environment
      exposures on the risk of disability pension. A representative sample of 8475
      employees of the total working population in Denmark were interviewed regarding
      work environment exposures and followed in a national register with data on
      granted disability pension. For women, approximately 34% of the disability
      pension cases were attributable to ergonomic work environment exposures. For men,
      21% of the disability pension cases were attributable to ergonomic work
      environment. Ergonomic work environment, especially physically demanding work,
      working with hands lifted and repetitive work, are areas of intervention at the
      workplace that can facilitate and prolong labour market participation. The study
      provides estimates for the association between ergonomic exposures at work and
      administrative, cost-related measures of work disability in a large population
      based longitudinal cohort study over 14 years. Approximately 21% for men and 34%
      for women of the disability pension cases were attributable to ergonomic work
      environment exposures.

PMID- 19851909
TI  - Effects of acoustic environment on work in private office rooms and open-plan
      offices - longitudinal study during relocation.
AB  - The aim was to determine how the perceived work environment, especially acoustic
      environment, and its effects differed in private office rooms and in open-plan
      offices. The subjects consisted of 31 workers who moved from private office rooms
      to open-plan offices and who answered the questionnaire before and after the
      relocation. Private office rooms were occupied only by one person while open-plan
      offices were occupied by more than 20 persons. Room acoustical descriptors showed
      a significant reduction in speech privacy after relocation. The noise level
      averaged over the whole work day did not change but the variability of noise
      level reduced significantly. Negative effects of acoustic environment increased
      significantly, including increased distraction, reduced privacy, increased
      concentration difficulties and increased use of coping strategies. Self-rated
      loss of work performance because of noise doubled. Cognitively demanding work and
      phone conversations were most distracted by noise. The benefits that are often
      associated with open-plan offices did not appear: cooperation became less
      pleasant and direct and information flow did not change. Nowadays, most office
      workers, independent of job type, are located in open-plan offices without the
      individual needs of privacy, concentration and interaction being analysed. This
      intervention study consisted of professional workers. Their work tasks mainly
      required individual efforts, and interaction between other workers was not of
      primary concern, although necessary. The results suggest that the open-plan
      office is not recommended for professional workers. Similar intervention studies
      should also be made for other job types.

PMID- 19851910
TI  - The effects of caffeine during exercise in fire protective ensemble.
AB  - To examine the effects of caffeine during exercise in fire protective ensemble
      (FPE), 10 healthy males completed 3 x 10 min bouts of treadmill exercise on two
      separate days. Sixty minutes prior to exercise either 6 mg/kg of caffeine (CAFF)
      or dextrose placebo (PLA) capsules were ingested (randomly assigned, double
      blind). End-exercise gastrointestinal temperature (T(gi)) was higher in CAFF
      compared to PLA (38.80 +/- 0.08 degrees C vs. 38.43 +/- 0.11 degrees C, p < or =
      0.01). Ventilation (V(E)) and tidal volume (V(t)) were also significantly higher
      in CAFF, which resulted in higher consumption of air from the self-contained
      breathing apparatus. While perceived exertion in the caffeine condition was
      decreased (p < or = 0.05) compared to placebo, the higher T(gi) values increased
      calculated physiological strain index in CAFF (p < or = 0.01). Caffeine appears
      to alter the physiological and psycho-physical responses to exercise in FPE and
      may influence factors related to work tolerance in firefighting. These findings
      are relevant to occupations such as firefighting where workers are encapsulated
      during exposure to heavy physical work and/or environmental heat. The results
      indicate that workers may be more susceptible to heat-related fatigue, illness or
      injury with ingestion of significant amounts of caffeine. To the authors'
      knowledge this is the first study involving humans and exercise to detect an
      increase in body temperature with caffeine ingestion.

PMID- 19851911
TI  - Advancing newborn health: The Saving Newborn Lives initiative.
AB  - Until recently, newborn health was virtually absent from the global health
      agenda. Now, assistance agencies, national governments and non-governmental
      organisations are increasingly addressing this previously neglected issue of
      close to four million newborns dying every year. The experience of the Saving
      Newborn Lives initiative documents some of the progress that has been made and
      the challenges and opportunities that lie ahead. Since the start of the
      initiative in 2000, targeted research, focused on overcoming the key barriers to
      improved newborn survival, has demonstrated low-cost, community-based
      interventions and strategies that can significantly reduce newborn mortality.
      Building on what has been learned from this and other efforts to date, the
      challenge now is to reach the millions of newborns still at risk.

PMID- 19851913
TI  - Obesity--the facts are now in--now what to do.

PMID- 19851914
TI  - Online illegal drug use information: an exploratory analysis of drug-related
      website viewing by adolescents.
AB  - Given the uncertain effects of antidrug media campaigns, and the ease of finding
      online illegal drug information, research is needed on the Internet role in
      disseminating drug information to youths. This exploratory study analyzes
      National Survey of Parents and Youth (NSPY) data on drug website viewing among 12
      18 year olds (N = 7,145). Approximately 10.4% reported drug-related website
      exposure: 5.4% viewed only websites that communicated how to avoid drugs or bad
      things about drugs (antidrug websites); 1.7% only viewed websites that
      communicated how to use drugs and good things about drugs (prodrug websites); and
      3.2% viewed both types of websites. The low rates of viewing antidrug websites
      occurred despite efforts in the National Youth Antidrug Media Campaign (NYAMC) to
      encourage youths to visit such websites. Prodrug website viewers had used
      inhalants and been offered marijuana, perceived little risk in trying marijuana,
      intended to use marijuana, had close friends who used drugs, reported low
      parental monitoring, and had been exposed to antidrug media messages. Viewing
      antidrug websites was related to gender, income, likelihood of using marijuana in
      the next 12 months, having close friends who use drugs and talking to friends
      about avoiding drugs, parental monitoring, and drug prevention exposure. Prior
      prevention exposure increased drug website viewing overall, perhaps by increasing
      general curiosity about drugs. Because adolescents increasingly seek health
      information online, research is needed on how they use the Internet as a drug
      information source, the temporal relationships of prevention exposure and drug
      website viewing, and the effects of viewing prodrug websites on drug risk.

PMID- 19851915
TI  - A front-of-pack nutrition logo: a quantitative and qualitative process evaluation
      in the Netherlands.
AB  - This study aimed to perform a quantitative and qualitative process evaluation of
      the introduction of the Choices logo, a front-of-pack nutrition logo on products
      with a favorable product composition, adopted by many food producers, retail and
      food service organizations, conditionally endorsed by the Dutch government,
      validated by scientists, and in the process of international dissemination. An
      online questionnaire was sent to adult consumers 4 months after the introduction
      of the logo (n = 1,032) and 1 year later (n = 1,127). Additionally, seven
      consumer focus groups (n = 41) were conducted to provide more insight into the
      questionnaire responses. Quantitative analyses showed that exposure to the logo
      had significantly increased. Elderly and obese respondents reported to be more in
      need of a logo than younger and normal-weight individuals. Women perceived the
      logo more attractive and credible than men did. Further qualitative analyses
      indicated that the logo's credibility would improve if it became known that
      governmental and scientific authorities support it. Elderly respondents indicated
      that they needed a logo due to health concerns. Consumers interested in health
      reported that they used the logo. Further research focusing on specific target
      groups, forming healthful diets, and health outcomes is needed to investigate the
      effectiveness of the Choices logo.

PMID- 19851916
TI  - Comparing computer-tailored, internet-based smoking cessation counseling reports
      with generic, untailored reports: a randomized trial.
AB  - To assess and compare the impact on quit attempts of online computer-tailored
      smoking cessation counseling reports and untailored reports, we performed a
      randomized controlled trial on a smoking cessation website in 2007-2008. After
      answering a questionnaire, current and former smokers were randomly assigned to
      immediately receiving either an online, individually tailored counseling report
      or a personalized but untailored generic report. Participants were invited by e
      mail to report any smoking in the previous 24 hours, 48 hours after baseline. We
      used an intention-to-treat analysis, where nonrespondents at follow-up were
      counted as smokers. There were 2,872 participants at baseline and 2,226 at follow
      up (78%). At baseline, there were 76% of current smokers (mean = 18
      cigarettes/day) and 24% of recent quitters (median = 7 days of abstinence). The
      same proportion of smokers in both study groups had made a 24-hour quit attempt
      at follow-up (12.1%, P = 1.0). In baseline recent quitters, lapse/relapse rates
      at follow-up were similar in both groups (tailored: 25.1%, untailored: 23.5%, P =
      0.64). We conclude that untailored reports were as effective as tailored reports
      in the short term. Even though these particular computer-tailored reports were
      not more effective than untailored reports, meta-analyses show that computer
      tailored documents are in general more effective than untailored ones.

PMID- 19851917
TI  - The content of cigarette counter-advertising: are perceived functions of smoking
      addressed?
AB  - Media campaigns can be an effective tool in reducing adolescent smoking. To
      better understand the types of ads that have been used in campaigns in the United
      States, a content analysis was conducted of ads available at the U.S. Centers for
      Disease Control and Prevention (CDC) Media Campaign Resource Center (MCRC; Waves
      1 through 7). A total of 487 ads were coded. Ads were coded for target audience,
      primary theme present in the ad, and sensation value-production techniques that
      have been demonstrated to attract attention and increase arousal. Primary themes
      extended earlier studies by focusing on the perceived functions of smoking
      (weight lose, stress management, controlling negative affect) as well as the
      traditional themes of industry attack, the health consequences of smoking,
      secondhand smoke, quitting, and the social image of smokers. A majority of ads
      were rated as having moderate sensation value, and ads targeted at teens and
      children were, on the average, higher in sensation value than those targeting
      general audiences. Changes across time suggest that campaigns are focusing more
      on adolescent smoking and relying more on attacking the tobacco industry.
      Research indicates that the functions of stress relief, mood regulation, and
      weight loss are strong reasons for initiating and continuing to smoke cigarettes;
      however, none of the 487 ads addressed these functional themes. Implications for
      developing campaigns that more closely relate to the functions of smoking are
      discussed.

PMID- 19851918
TI  - Developing a global health diplomacy supply chain--a viable option for the United
      States to curb extremism.
AB  - This study examines the idea of developing a global health diplomacy supply chain
      as an important foreign policy approach with the aim of improving the lives of
      vulnerable populations and serving the best interests of the United States. The
      study was based on the review of academic literature, news events, and military
      communiques, and historical writings were studied to determine the feasibility of
      the idea and the extent of costs and benefits of such an endeavor. An integrated
      strategic business model, supported by a medical care delivery process, was
      developed to create a framework for a feasible global health diplomacy supply
      chain. The findings indicate that extremism can be contained by creating and
      efficiently executing an effective supply chain to get medical care units to
      those that need them. The limitations are the potential exit strategies required,
      the tactical abilities, and diplomatic techniques needed in order to create
      positive diplomatic change in aid distribution. Managers must consider how supply
      chains will affect other organizations giving aid and the potential public
      response. Moreover, determining the level of care necessary to achieve the
      greatest positive health diplomacy continues to require vigilant scrutiny over
      the potential cost/benefit analysis. The analysis is valuable to policymakers
      considering the impacts of health diplomacy by utilizing supply chain management.

PMID- 19851919
TI  - Improving reproductive health knowledge in rural China--a web-based strategy.
AB  - In China, one of the major problems in upgrading rural health services is the
      difficulty of communicating between the rural and urban areas. Enabling local
      agencies to access the Internet in resource-poor areas can provide an efficient
      means of diffusing current training and information and will have far-reaching
      policy implications. To test the feasibility of using the Internet to deliver
      needed health information to the countryside, the UCLA School of Public Health
      and the Institute of Health Studies of Kunming Medical College (IHS-KMC)
      collaborated in an experimental website project to improve the quality of
      reproductive health services to promote women's health in three rural counties of
      Yunnan. The project involved the county government and the Bureau of Public
      Health, the Bureau of Family Planning; the Bureau of Education, Women's
      Federation, and the Maternal and Child Health Station targeting village health
      workers and teachers; women's cadres. Three counties, matched on socioeconomic
      status, participated in the study and were randomized to receive three programs.
      Nanhua County received computer skill training and logistic support including a
      planning workshop for information diffusion. Mouding County received computers
      only. Dayao, the control county, did not receive the full program until the
      conclusion of the project. The study demonstrated that the use of a website to
      disseminate health information in remote rural areas is not only feasible but
      that it also will be enthusiastically adopted by local health workers and
      interested parties. Moreover, the knowledge was diffused from the primary
      population of village doctors, family planning workers, women's cadres, and
      teachers to the secondary population of villagers and students.

PMID- 19851921
TI  - Comparision of the volatile components of unripe and ripe Japanese apricot
      (Prunus mume Sieb. et Zucc.).
AB  - The composition of the volatile components from unripe (I) and ripe (II) Japanese
      apricot (Prunus mume Sieb. et Zucc.) have been investigated. Seventy-six volatile
      components were identified, 25 for the first time as volatile constituents of
      Japanese apricot. The main components were benzaldehyde (I, 59.16%; II, 1.81%),
      isolongifololyl acetate (II, 19.21%), palmitic acid (I, trace; 10.22%), linalool
      (I, 9.93%; II, 7.34%), and butyl acetate (II, 8.30%). Unripe Japanese apricot
      have a green colour due to the main components being aldehydes. On the contrary,
      ripe Japanese apricot had a fruity note due to the increase of the ratio of
      esters during ripening.

PMID- 19851922
TI  - Microsphaeropsisin A, a new sesquiterpenoid isolated from the mangrove endophytic
      fungus (No. DZ39).
AB  - A new sesquiterpenoid compound, microsphaeropsisin A (1), together with three
      known dihydroisocoumarin compounds, (R)-mellein (2), 4-hydroxymellein (3) and 5
      hydroxymellein (4) were isolated from the culture of the mangrove fungus (No.
      DZ39). The structure of the new compound was established by comprehensive
      spectral analysis, especially 2D NMR spectroscopy.

PMID- 19851923
TI  - Persicasulphide C, a new sulphur-containing derivative from Ferula persica.
AB  - A new sulphur-containing compound, persicasulphide C, was isolated from the roots
      of Ferula persica, and its structure was characterised by 1D- and 2D-NMR
      spectroscopy as well as HRMS. In addition, closer inspection of NMR spectra of
      the previously reported polysulphides (persicasulphides A and B) revealed that
      their structures are slightly different from those reported. In this article, the
      correct structures of persicasulphides A and B are also presented.

PMID- 19851924
TI  - Separation and elucidation of anthocyanins in the fruit of mockstrawberry
      (Duchesnea indica Focke).
AB  - Anthocyanin pigments in the fruit of mockstrawberry (Duchesnea indica Focke),
      were extracted with 0.1% HCl in ethanol, and the crude anthocyanin extract was
      purified by a C18 Sep-Pak cartridge open-column chromatography. High-performance
      liquid chromatography (HPLC) with photodiode array detection and mass
      spectrometry (MS) was applied for the isolation and composition analysis of
      anthocyanins in the fruit of mockstrawberry and their aglycones from acid
      hydrolysis. Three anthocyanins were found in the fruit of mockstrawberry and they
      were identified as cyanidin 3-O-rutinoside (61%), peonidin 3-O-rutinoside (34%),
      and petunidin 3-O-rutinoside (5%), respectively, by spectroscopic methods (UV-vis
      and MS). The two major anthocyanins were isolated by preparative HPLC, and their
      chemical structures were further characterised by Heuro(1) NMR. On the basis of
      chromatographic data, the total anthocyanin content was 205 mg g(-1) of the fresh
      fruit of mockstrawberry.

PMID- 19851925
TI  - A new indole alkaloid from Alstonia scholaris.
AB  - A new indole alkaloid, N-formylscholarine, together with picrinine, strictamine
      and nareline has been isolated from the fruit pods of Alstonia scholaris, and
      their structures were established by various spectral data. This is the first
      report of these alkaloids in A. scholaris fruit pods.

PMID- 19851926
TI  - Two new triterpenoid isomers from Nerium oleander leaves.
AB  - Two new triterpenoid isomers alpha-neriursate (1) and beta-neriursate (2) have
      been isolated from the fresh, uncrushed leaves of Nerium oleander and their
      structures elucidated as 3alpha-acetophenoxy-urs-12-en-28-oic acid and 3beta
      acetophenoxy-urs-12-en-28-oic acid, respectively. The structure elucidation is
      based on spectroscopic methods, including 1D ((1)H NMR, (13)C NMR) and 2D ((1)H
      (1)H COSY, NOESY, HMQC, HMBC and J-resolved) NMR data and chemical
      transformation.

PMID- 19851927
TI  - Bioactive flavonoids from Satureja atropatana Bonge.
AB  - From the ethyl acetate and methanol extract of the aerial parts of Satureja
      atropatana Bonge, which belongs to the Lamiaceae family, four flavonoids were
      isolated. Their structures were determined to be 5,6,3'-trihydroxy-7,8,4'
      trimethoxyflavone (1), 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone or 5
      desmethoxynobiletin (2), 5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone or thymonin
      (3) and luteolin (4) using (1)H and (13)C-NMR and MS spectra. Brine shrimp
      cytotoxicity effects of the crude extracts and isolated compounds were examined.
      Berberine hydrochloride (LC(50) = 26 microg mL(-1)) was used as a positive
      control. Among them, compounds 2 (199 microg mL(-1)) and 3 (157 microg mL(-1))
      were effective against Artemia salina larva.

PMID- 19851928
TI  - Minor sesquiterpenes from the volatile oil from leaves of Guarea guidonia Sleumer
      (Meliaceae).
AB  - The essential oil from leaves of Guarea guidonia was subjected to chromatographic
      separation procedures to afford nine sesquiterpenes; two of them are new
      eudesmane derivatives. The chemical structures of the obtained compounds were
      characterised by spectrometric analysis, mainly mass spectrometry and NMR.

PMID- 19851929
TI  - A new myricetin-rhamnodiglucoside from Camellia sinensis.
AB  - The isolation and structural elucidation of the novel myricetin-3-O-[beta-D
      glucopyranosyl-(1 --> 3)-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D
      glucopyranoside] from tea (Camellia sinensis (L.) O. Kuntze) by means of HPLC
      MS/MS and various NMR techniques is described. The compound was not present in
      all tea samples analysed. In the case of white tea, it was detected in 20 out of
      40 samples analysed (35-255 mg kg(-1)), in green tea it was detected in 18 out of
      35 samples in the same concentration range (37-205 mg kg(-1)), while it was found
      only in 1 sample (51 mg kg(-1)) of 5 black teas analysed.

PMID- 19851930
TI  - Bacterial production of tetrodotoxin in the pufferfish Arothron hispidus.
AB  - This study evaluates the presence, location and production source of tetrodotoxin
      (TTX) in two species of pufferfish, Diodon histrix and Arothron hispidus, common
      to Hawaiian waters. Organs from each fish were analysed for TTX and used to
      isolate bacteria for evaluation of possible TTX production. Comparative analyses
      of extracts of fish and bacterial culture media were performed with liquid
      chromatography-mass spectrometry (LC-MS) and a sodium channel specific bioassay.
      Bacterial cultivation experiments were performed in two different growth media
      and bacteria were identified through sequence homology of the 16S rRNA gene.
      Forty-two and forty-seven distinct strains were cultivated from D. histrix and A.
      hispidus, respectively. However, no commonality was found between the populations
      of bacteria isolated from the two fish. TTX was detected only in A. hispidus and
      was present in the flesh, pectoral fin and kidneys, as well as the skin slime.
      Sixteen of the forty-seven bacterial species isolated from A. hispidus were
      cultivated for further evaluation of TTX production. Among these sixteen
      bacterial species, Vibrio harveyi strains isolated from the skin slime and
      kidneys of A. hispidus were found to produce TTX, being the source of TTX
      produced in the pufferfish.

PMID- 19851931
TI  - Synthesis and characterisation of seleno-Cynomorium songaricum Rupr.
      polysaccharide.
AB  - In this article, the structural properties of Cynomorium songaricum Rupr.
      polysaccharide (CSP) after selenylation were investigated. The crude
      polysaccharide was obtained from C. songaricum Rupr. by water extraction followed
      by ethanol precipitation and freeze vacuum drying. Then selenylation of CSP has
      been accomplished by employing sodium selenite to modify the polysaccharide under
      the catalysis of nitric acid-barium chloride. After selenylation, the sugar
      content and the molecular weight increased but the protein content reduced. The
      maximum selenic content determined by ICP-AES was 2925 microg g(-1). The selenide
      CSP (Se-CSP) was characterised by the methods of UV spectra, FT-IR, Raman spectra
      and X-ray photoelectron spectroscopy. The results showed that the hydroxyl
      hydrogen of the sugar moieties was substituted by Se=O. Thermal stability of Se
      CSP was also measured by TG-DTA.

PMID- 19851932
TI  - A chromanone alkaloid from Derris ovalifolia stem.
AB  - From the stem of Derris ovalifolia, a new chromanone alkaloid characterised as 7
      methoxy-3-[1-(3-pyridyl)methylidene]-4-chromanone (1) was isolated along with
      four known compounds, dehydrotoxicarol (2), dehydrodeguelin (3), toxicarol
      isoflavone (4) and indole-3-carbaldehyde (5). Their structures were determined on
      the basis of spectral data interpretation. The structure of compound 1 has also
      been confirmed by synthesis.

PMID- 19851933
TI  - Trends in senescent life expectancy.
AB  - The distinction between senescent and non-senescent mortality proves to be very
      valuable for describing and analysing age patterns of death rates. Unfortunately,
      standard methods for estimating these mortality components are lacking. The first
      part of this paper discusses alternative methods for estimating background and
      senescent mortality among adults and proposes a simple approach based on death
      rates by causes of death. The second part examines trends in senescent life
      expectancy (i.e., the life expectancy implied by senescent mortality) and
      compares them with trends in conventional longevity indicators between 1960 and
      2000 in a group of 17 developed countries with low mortality. Senescent life
      expectancy for females rises at an average rate of 1.54 years per decade between
      1960 and 2000 in these countries. The shape of the distribution of senescent
      deaths by age remains relatively invariant while the entire distribution shifts
      over time to higher ages as longevity rises.

PMID- 19851934
TI  - The effects of child-related benefits and pensions on fertility by birth order: a
      test on Hungarian data.
AB  - Using aggregate time-series data from post-war Hungary, we investigated the
      effect of child-related benefits and pensions on overall fertility and fertility
      by birth order. The results indicate moderate effects that are robust across a
      wide range of specifications. According to our estimates, a 1-per-cent increase
      in child-related benefits would increase total fertility by 0.2 per cent, while
      the same increase in pensions would decrease fertility by 0.2 per cent. The
      magnitude of both effects increases by birth order; this is more robust for child
      related benefits.

PMID- 19851935
TI  - The joint effect of maternal malnutrition and cold weather on neonatal mortality
      in nineteenth-century Venice: an assessment of the hypothermia hypothesis.
AB  - Recent studies stress the key role played by neonatal mortality in the
      demographic regime of north-eastern Italy. In particular, during the period 1700
      1830 this area experienced a dramatic upsurge in winter neonatal deaths, pushing
      overall neonatal and infant mortality rates to the highest in Italy and most of
      Europe. Scholars have argued that this trend was caused by a general
      pauperization leading to widespread maternal malnutrition, low birth weight, and
      an increased frequency of winter neonatal deaths caused by the higher sensitivity
      of low-birth-weight infants to the cold. The study presented here tested this
      hypothesis using a large mid-nineteenth-century longitudinal sample of the
      Venetian population. Two alternative measures of maternal malnutrition were
      applied: chronic undernourishment and temporary nutritional stress during late
      gestation. Only the second condition is significantly associated with higher
      neonatal mortality when outside temperatures were low. This is consistent with
      mechanisms of neonatal thermoregulation but casts doubt on the pauperization
      hypothesis suggested by other studies.

PMID- 19851936
TI  - Employment first, then childbearing: women's strategy in post-socialist Poland.
AB  - Poland experienced a rapid fertility decline after the end of the socialist
      regime in 1989. At the same time, it became much more difficult, especially for
      women, to act on their determination to find and keep paid employment. To
      investigate whether women postponed childbearing until they found a job, we
      undertook a simultaneous estimation of transitions to childbirth and entry to and
      exit from employment. The results reveal a strong incompatibility between
      childbearing and employment, but also that employment does not function as a
      barrier to childbearing but rather that it is an important precursor when women
      plan how to reconcile their intentions to work and to have children. We conclude
      that better prospects for women's employment could result in increased fertility.

PMID- 19851937
TI  - Ethnic diversity, traditional norms, and marriage behaviour in Indonesia.
AB  - What role do cultural norms play in shaping individual behaviour and how does
      this relationship change with rapid socio-economic development? While
      modernization and convergence theories predict a weakened relationship between
      culture and behaviour as individuals rely less on family and community members
      for economic opportunities, recent research suggests that such norms can persist
      and continue to influence behaviour. We explored this question for Indonesia,
      asking whether cultural norms for age at marriage and post-marriage residence-as
      embodied in local ethnicity-based laws and customs known as 'adat'-relate to
      actual marriage behaviour. We demonstrate that adat norms are strong predictors
      of marriage behaviour, both over time and net of large increases in educational
      attainment. Our results suggest more generally that traditional marriage norms
      can persist even when a society is in the process of rapid socio-economic
      development.

PMID- 19851940
TI  - Fairness concerns predict medial frontal negativity amplitude in ultimatum
      bargaining.
AB  - Despite evidence that anterior cingulate cortex (ACC) activity is related to
      social exclusion, rejection and unfairness, evidence that medial frontal
      negativity (MFN), which has its source in the ACC, reflects these constructs
      remains unforthcoming. In the present study, subjects participated as recipients
      in an ultimatum game, while we recorded their electro-encephalogram (EEG).
      Participants responded to fair and unfair offers from different human proposers.
      In addition, participants rated themselves on a measure evaluating their concern
      for fairness. Results showed that MFN amplitude was more pronounced for unfair
      offers compared to fair offers. Moreover, this effect was shown to be most
      pronounced for subjects with high concerns for fairness. Our findings suggest
      that the MFN not only reflects whether outcomes match expectations, but also
      reflects whether the process by which these outcomes came about matches a social
      or even a moral norm. In addition, the present results suggest that people in
      bargaining situations are not only concerned with their own outcomes, but are
      also concerned with the fairness of the process that resulted in these outcomes.

PMID- 19851938
TI  - Individual capital and cognitive ageing in Guatemala.
AB  - Using data from adults 50 years and older in Guatemala (N = 643), we assessed to
      what extent measures of individual capital-economic, social, intellectual, and
      biological-were associated with and account for variation in cognitive
      functioning, as measured by the Modified Mini-Mental Status Exam (M-MMSE).
      Measures of these components of individual capital are positively associated with
      cognitive functioning, and together with other attributes, account for 29.6 per
      cent of its variance. Schooling accounts for the largest unique share (5.3 per
      cent) of the variance, followed by household standard of living (2.0 per cent),
      church attendance (1.3 per cent), and z-score for height (0.9 per cent). In a
      setting like Guatemala-with low schooling, widespread poverty, malnutrition, and
      infectious disease-early life investments that increase schooling and improve
      nutrition may be valuable as investments to mitigate cognitive impairment in
      older adults and its contribution to the disease burden.

PMID- 19851941
TI  - Applying an exemplar model to the artificial-grammar task: String completion and
      performance on individual items.
AB  - Jamieson and Mewhort (2009a) demonstrated that performance in the artificial
      grammar task could be understood using an exemplar model of memory. We reinforce
      the position by testing the model against data for individual test items both in
      a standard artificial-grammar experiment and in a string-completion variant of
      the standard procedure. We argue that retrieval is sensitive to structure in
      memory. The work ties performance in the artificial-grammar task to principles of
      explicit memory.

PMID- 19851942
TI  - Women's sexual orientation and health: results from a Canadian population-based
      survey.
AB  - The current study sought to determine whether health status and health risk
      behaviors of Canadian women varied based on sexual identity. This was a cross
      sectional analysis of data from the Canadian Community Health Survey: cycle 2.1,
      a national population-based survey designed to gather health data on a
      representative sample of over 135,000 Canadians including 354 lesbian
      respondents, 424 bisexual women respondents, and 60,937 heterosexual women
      respondents. Sexual orientation was associated with disparities in health status
      and health risk behaviors for lesbian and bisexual women in Canada. Bisexual
      women were more likely than lesbians or heterosexual women to report poor or fair
      mental and physical health, mood or anxiety disorders, lifetime STD diagnosis,
      and, most markedly, life-time suicidality. Lesbians and bisexual women were also
      more likely to report daily smoking and risky drinking than heterosexual women.
      In sum, sexual orientation was associated with health status in Canada. Bisexual
      women, in particular, reported poorer health outcomes than lesbian or
      heterosexual women, indicating this group may be an appropriate target for
      specific health promotion interventions.

PMID- 19851943
TI  - A comparison of the occurrence and perceived stress of major life events in black
      and white women.
AB  - PURPOSE: To describe the occurrence and perceived stress of major life events,
      and to investigate whether adjusting for socioeconomic status reduced
      race/ethnicity differences. METHODS: Black (n = 639) and white (n = 419) women
      aged 35-49 years responded to 14 major life event questions within the domains of
      employment, health, relationship, finance, residential change, and crime. MAIN
      FINDINGS: The total number of life events did not differ by race/ethnicity, but
      black women reported significantly more events in the domains of relationship,
      financial, and residential change than white women. White women generally
      reported higher stress for a given event than black women, although for
      "residential change" black women reported more severe stress than the white
      women. CONCLUSIONS: Inclusion of both the occurrence and perceived stress of
      major life events can improve our understanding of how this stressor may affect
      health.

PMID- 19851944
TI  - Perceived benefits of online support groups for women with metastatic breast
      cancer.
AB  - Women with metastatic breast cancer (MBC), a life-threatening illness, stand to
      benefit a great deal from online support groups, but none have been studied
      specifically within this population. The present mixed-method study was carried
      out to determine which therapeutic factors occurred in online MBC support groups,
      and to see how such factors might have acted to benefit participants.
      Participants were 20 women with MBC who participated in online peer support
      groups. Most reported benefiting in some way from their groups. Six therapeutic
      factors theorized to be helpful in online support groups and cancer support
      groups were present in the groups studied: group cohesiveness, information
      exchange, universality, instillation of hope, catharsis, and altruism. However,
      although participants reported being able to discuss many other concerns freely,
      they had difficulty discussing death and dying, which are critical issues for
      this category of women with BC.

PMID- 19851945
TI  - Menstrual problems and health seeking in Sri Lanka.
AB  - Menstruation is associated with some morbidity, although it is a normal
      physiological event. In this article, we draw on qualitative research conducted
      in Sri Lanka in 2006-2007, which included eight key informant interviews with
      healthcare providers, six focus group discussions with eight women in each, and
      five case studies. We describe and analyze women's perceptions of menstruation
      and menstrual problems, their help-seeking behaviors to reduce these health
      problems, and the consequences of them on their lives. The majority of women
      perceived menstruation as a physiological process and related problems to changes
      in hormone levels, pathological conditions of the uterus, and the side effects of
      contraceptive methods. Menstrual problems significantly affected their daily
      activities, mental well-being, social life, and sexual life, but few sought
      medical advice to resolve these problems. Implications of the findings included
      the need for health care providers and educators to provide accurate information
      on menstruation to girls and women to enable them to identify normal variation of
      menstruation and to take appropriate action regarding health care.

PMID- 19851946
TI  - Risk messages about HPV, cervical cancer, and the HPV vaccine Gardasil: a content
      analysis of Canadian and U.S. national newspaper articles.
AB  - The human papillomavirus vaccine (Gardasil) is a significant advancement in
      women's health. We compared the reporting of fear-inducing messages about human
      papillomavirus, cervical cancer, and the human papillomavirus vaccine in Canadian
      and U.S. national newspapers between January 2006 and December 2007. Significant
      differences between countries were found in the number of articles containing
      fear messages about human papillomavirus, cervical cancer, and the human
      papillomavirus vaccine. Educational level of readability was higher than
      recommended for the public, and the emotional tone of the articles became
      progressively negative over time. Our findings suggest that public discussion of
      some elements of the human papillomavirus vaccine message that could cause alarm
      or worry for women may need to be addressed within political and cultural
      contexts.

PMID- 19851947
TI  - Creating the "desired mindset": Philip Morris's efforts to improve its corporate
      image among women.
AB  - Through analysis of tobacco company documents, we explored how and why Philip
      Morris sought to enhance its corporate image among American women. Philip Morris
      regarded women as an influential political group. To improve its image among
      women, while keeping tobacco off their organizational agendas, the company
      sponsored women's groups and programs. It also sought to appeal to women it
      defined as "active moms" by advertising its commitment to domestic violence
      victims. It was more successful in securing women's organizations as allies than
      active moms. Increasing tobacco's visibility as a global women's health issue may
      require addressing industry influence.

PMID- 19851949
TI  - Testing bilingual speakers: challenges and potential solutions. Preface.

PMID- 19851950
TI  - Bilingual children and communication disorders: a 30-year research retrospective.
AB  - We present a review of the empirical literature at the intersection of
      bilingualism and pediatric communication disorders. A computer search of six
      electronic databases was done to identify studies published in English since 1950
      that directly investigated some aspect of speech, language, or cognitive
      performance in developing bilinguals and children with communication impairments.
      The computer search yielded 116 non-duplicated articles, the first published in
      1978. An article review by the authors further reduced the number of studies
      meeting search criteria to 64. A majority of studies focused on primary
      developmental language impairment (LI) and children learning two languages
      sequentially. Spanish and English were the most frequent combination of languages
      for bilingual participants. Collective study findings are presented with respect
      to trends, clinical implications, and areas for future research.

PMID- 19851951
TI  - Using language sampling in clinical assessments with bilingual children:
      challenges and future directions.
AB  - Current language tests designed to assess Spanish-English-speaking children have
      limited clinical accuracy and do not provide sufficient information to plan
      language intervention. In contrast, spontaneous language samples obtained in the
      two languages can help identify language impairment with higher accuracy. In this
      article, we describe several diagnostic indicators that can be used in language
      assessments based on spontaneous language samples. First, based on previous
      research with monolingual and bilingual English speakers, we show that a verb
      morphology composite measure in combination with a measure of mean length of
      utterance (MLU) can provide valuable diagnostic information for English
      development in bilingual children. Dialectal considerations are discussed.
      Second, we discuss the available research with bilingual Spanish speakers and
      show a series of procedures to be used for the analysis of Spanish samples: (a)
      limited MLU and proportional use of ungrammatical utterances; (b) limited
      grammatical accuracy on articles, verbs, and clitic pronouns; and (c) limited
      MLU, omission of theme arguments, and limited use of ditransitive verbs. Third,
      we illustrate the analysis of verb argument structure using a rubric as an
      assessment tool. Estimated scores on morphological and syntactic measures are
      expected to increase the sensitivity of clinical assessments with young bilingual
      children. Further research using other measures of language will be needed for
      older school-age children.

PMID- 19851952
TI  - Cross-linguistic universals in reading acquisition with applications to English
      language learners with reading disabilities.
AB  - There is a considerable gap in English reading achievement between English
      language learners and native speakers in the United States. Differentiation of
      whether English language learners' struggles are symptomatic of reading
      disability or related to second language acquisition is often challenging. These
      issues highlight the need for increased insight into reading development and
      disability in this population. The purpose of this article is to provide an
      overview of cross-linguistic universals in reading acquisition, how reading
      disabilities manifest in various languages, and whether diagnostic and
      instructional approaches that are effective for native English speakers are also
      appropriate for English-language learners. Recommendations for assessment and
      intervention practices for at-risk and reading-disabled English-language learners
      are provided.

PMID- 19851953
TI  - Multicultural issues in test interpretation.
AB  - Designing the ideal test or series of tests to assess individuals who speak
      languages other than English is difficult. This article first describes some of
      the roadblocks-one of which is the lack of identification criteria for language
      and learning disabilities in monolingual and bilingual populations in most
      countries of the non-English-speaking world. This lag exists, in part, because
      access to general education is often limited. The second section describes tests
      that have been developed in the United States, primarily for Spanish-speaking
      individuals because they now represent the largest first-language majority in the
      United States (80% of English-language learners [ELLs] speak Spanish at home). We
      discuss tests developed for monolingual and bilingual English-Spanish speakers in
      the United States and divide this coverage into two parts: The first addresses
      assessment of students' first language (L1) and second language (L2), usually
      English, with different versions of the same test; the second describes
      assessment of L1 and L2 using the same version of the test, administered in the
      two languages. Examples of tests that fit a priori-determined criteria are
      briefly discussed throughout the article. Suggestions how to develop tests for
      speakers of languages other than English are also provided. In conclusion, we
      maintain that there will never be a perfect test or set of tests to adequately
      assess the communication skills of a bilingual individual. This is not surprising
      because we have yet to develop an ideal test or set of tests that fits
      monolingual Anglo speakers perfectly. Tests are tools, and the speech-language
      pathologist needs to know how to use those tools most effectively and equitably.
      The goal of this article is to provide such guidance.

PMID- 19851954
TI  - Considerations in working successfully with culturally/linguistically diverse
      families in assessment and intervention of communication disorders.
AB  - The framework of the International Classification of Functioning is used to
      explain the importance of understanding cultural behaviors, values, and beliefs
      when assessing and providing intervention for communication impairments in
      persons from culturally/linguistically diverse backgrounds. The use of skilled
      dialogue in developing anchored understanding of a family's culture is described.
      By using their anchored understanding, professionals can create a 3rd space as a
      way to integrate the differing perspectives of families and professionals to
      provide culturally/linguistically appropriate assessments and interventions.

PMID- 19851955
TI  - Pulsatility of an intracavernous aneurysm demonstrated by dynamic 320-detector
      row CTA at high temporal resolution.
AB  - Studying the flow dynamics of intracranial aneurysms and the associated
      pulsatility of the aneurysm wall may help to risk-stratify unruptured aneurysms.
      Currently, in-vivo methods that visualize aneurysm wall movement at high temporal
      resolution are not yet fully established. We describe a patient with an
      intracavernous aneurysm in whom the area of increased aneurysm pulsatility as
      demonstrated by high-temporal resolution CTA was identical to the area of
      aneurysm growth on follow-up. A 35-year-old man presented with headaches and a
      sixth nerve palsy. CT including dynamic CTA demonstrated a pulsating
      intracavernous aneurysm. On follow-up one week later, the patient had developed
      hypesthesia in his V1 and V2 distribution and repeat imaging demonstrated
      aneurysm growth in the aneurysm part that demonstrated pulsatile movements on
      dynamic CTA. Stent-assisted coiling of the aneurysm was performed and led to
      clinical improvement. Dynamic CTA was performed using a 320-detector row CT
      following continuous rotational scanning during the administration of contrast
      with subsequent image reconstructions at 100 msec intervals. Dynamic CTA can
      demonstrate aneurysm pulsations that, as in the present case of a patient with a
      giant intracavernous aneurysm, were associated with aneurysm growth in the area
      of maximum pulsation. We hypothesize that this technique may predict aneurysm
      growth and may therefore be helpful in the non-invasive in vivo assessment of
      individual aneurysm features such as dome and bleb pulsations in both unruptured
      and ruptured aneurysms.

PMID- 19851956
TI  - Are there false-negative results of motor evoked potential monitoring in brain
      surgery?
AB  - OBJECT: The present study explores the causes of occasional postoperative pareses
      despite unchanged or fully recovered intraoperative motor evoked potentials
      (MEPs) in supratentorial brain surgeries. METHODS: In a prospective,
      observational design, MEP monitoring results, motor outcome, and perioperative
      imaging were correlated in 200 procedures for brain tumours and cortical
      dysplasias critically related to motor areas and pathways. RESULTS: Persisting
      pareses after unchanged or recovered MEPs occurred in four cases due to delayed
      ischemia, or venous congestive oedema. Transient new deficit in four cases after
      stable MEP monitoring occurred due to inadvertently strong stimulation bypassing
      the target lesion, due to marked postresectional oedema, and after cortical
      transsections for alleviation of epilepsy. DISCUSSION AND CONCLUSIONS: With
      technically adequate MEP monitoring, truly false-negative results missing
      manifest corticospinal impairment do not occur. However, sustained vascular
      dynamics (vasospasm, congestive oedema) may cause delayed pareses which are
      missed, or hardly reflected by intraoperative MEP changes. Even minor MEP changes
      must therefore be observed to prevent impending motor deficit.

PMID- 19851957
TI  - Nonconvulsive status epilepticus as a possible cause of coma in neurosurgical
      intensive care.
AB  - Nonconvulsive status epilepticus (NCSE) can occur in comatose patients without
      clinical signs of seizure activity. We evaluated the occurrence of NCSE in
      patients who were admitted to our neurosurgical intensive care unit between 1998
      and 2000. EEGs were obtained from 158 patients with head trauma, spontaneous
      bleeding or brain tumour. Patients with clinically apparent seizure activity or
      no electrophysiological signs of seizure activity were excluded from the study.
      Epileptiform activity was seen in 28 out of 158 patients. 11/28 of these patients
      had a Glasgow-Coma-Scale (GCS) Score below 9 and showed continuous epileptiform
      discharge without clinical signs of seizure activity (NCSE). The clinical status
      of 4 of these 11 NCSE patients improved after initiation of anticonvulsive
      medication. NCSE may be an under-recognised cause of coma in neurosurgical
      intensive medicine. EEG should be included in the routine evaluation of comatose
      patients, even if clinical seizure activity is not apparent.

PMID- 19851958
TI  - Effects of GYKI 52466 on early vasospasm in rats.
AB  - OBJECTIVE: The pathogenesis and treatment of cerebral vasospasm (CV) after
      subarachnoid hemorrhage (SAH) remains a matter of discussion. The authors
      investigated the efficacy of GYKI 52466, a 2,3-benzodiazepine that is a selective
      and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA)
      receptor antagonist, in a rat femoral artery vasospasm model. METHODS: Twenty
      seven Wistar albino rats were used in this study. The animals were divided into 3
      groups of 9 animals each: sham-operated control (group 1), vasospasm group (group
      2), and vasospasm-plus-treatment group (group 3). In groups 2 and 3, autologous
      blood (0.1 mL) was applied to a 1-cm segment of the femoral artery, which was
      then wrapped with a silicone cuff. One minute after blood application, the rats
      in group 3 received an intraperitoneal injection of 15 mg/kg GYKI 52466 every 12
      h for 24 h. Responses to blood application and treatment were evaluated with
      light and electron microscopy examinations of femoral artery specimens at 72 h.
      RESULTS: On light microscope examination, the mean diameters of the arterial
      lumens in groups 1, 2, and 3 were 514.47+/-15.3, 317.63+/-12.1, and 503.91+/-9.6
      microm, respectively. At 24 h, the mean arterial wall thickness in group 1 was
      77.69+/-4.2 microm. This mean thickness in group 2 increased to 164.82+/-9.1
      microm. After GYKI treatment in group 3, the mean arterial wall thickness
      measured 95.37+/-5.3 microm. In group 2 rats, electron microscopy demonstrated
      various changes including marked luminal narrowing and increased wall thickness
      in the femoral arterial wall. The most striking finding were the degenerative
      changes in the endothelium, which presented as a corrugated appearance of the
      internal elastic lamina. Rats in group 3 had endothelia that were slightly
      constricted and smooth muscle cells that were relaxed; changes in the vessel wall
      and internal elastic lamina were less prominent in these rats than in the rats of
      group 2. CONCLUSIONS: The results of the present study suggest that GYKI 52466
      inhibited AMPA receptors and induced relaxation of smooth muscle cells in the
      wall of the femoral artery in a rat model. This substance may be a protective and
      therapeutic agent in the treatment of cerebral vasospasm.

PMID- 19851959
TI  - Completely ossified pseudomeningocele, a rare complication after spinal surgery.
AB  - BACKGROUND: We report the rare case of an ossified pseudomeningocele following
      laminectomy. The extradural pseudocyst has completely ossified without an overt
      communication to the subarachnoid space. CASE REPORT: In 1986, a 41 year-old
      woman suffered from spinal stenosis at levels L3-5 and was treated by
      laminectomy. A cerebrospinal fluid (CSF) leakage was observed postoperatively. A
      follow-up CT scan eleven years after surgery showed an ossified pseudomeningocele
      in the operated region. However, in our case no surgical resection was performed
      since the patient suffered only from diffuse back pain without sciatica or any
      neurological deficit. In 2009 the patient continues to be neurologically intact
      without a change in clinical complaints. Hence, the file was closed after 23
      years without neurosurgical intervention. DISCUSSION: Seven cases of ossified
      pseudomeningocele have been previously described in the literature and all were
      operated on. However, our case shows that ossified extradural pseudocysts do not
      require operation in every case.

PMID- 19851960
TI  - Ileorectal anastomotic obstruction treated with a dual endoscopic
      transillumination technique.

PMID- 19851961
TI  - [The investigation of Toxoplasma gondii seropositivity in women in the Kayseri
      province].
AB  - Toxoplasmosis is a parasitic disease caused by a protozoon, Toxoplasma gondii.
      Its prevalence varies according to geographical status, age, eating habits and
      life style. The aim of this study was to determine seropositivity of Toxoplasma
      gondii in women who presented at the Kayseri Obstetric and Children Hospital.
      Anti-Toxoplasma IgG and IgM antibodies were investigated with the microparticle
      enzyme immunoassay (MEIA) method in sera of 2235 women from August 2005 to
      December 2008. It was found that Toxoplasma seropositivity was 33.42% and that
      increases in the seropositivity rate is statistically significant in regard to
      the increase in age (p<0.05).

PMID- 19851962
TI  - [Comparison of commercial IFA, IHA and in-house IFA tests in the diagnosis of
      cystic echinococosis].
AB  - Hydatidosis is an endemic illness in many regions of world. Several
      serodiagnostic techniques have been evaluated for the diagnosis of cystic hydatid
      disease caused by Echinococcus granulosus. The aim of this study was to assess
      the efficiency of the commercial fluorescent antibody test (IFAT), indirect
      hemaglutination test (IHAT) and in-house IFA tests. For this purpose sera from
      one hundred patients who had been given a diagnosis of hydatid cyst by surgery
      were used. In-house IFA was developed using the germinal membrane of Echinococcus
      granulosus and sera were studied by the three different methods. As a result, the
      specificity of commercial IFA, IHA and in-house IFA was found to be 100% and
      sensitivities of these tests were 87.7%, 74.6% and 83.3% respectively. In
      conclusion, in-house IFA test is a useful and cost effective but difficult test
      to prepare for the routine laboratory.

PMID- 19851963
TI  - The detection of Echinococcus granulosus strains using larval rostellar hook
      morphometry.
AB  - The purpose of this study was to determine the morphometrical characteristics of
      the larval hooks of Echinococcus granulosus in Turkey. The number of rostellar
      hooks (NH) and the total length of long blades, length of the blade of the long
      hooks, the total length of small blades and the length of the blade of the small
      hooks were measured in sheep and cattle isolates. The principal component and
      discriminant function analyses were used to analyze the data. Rostellar structure
      of protoscoleces was very similar in the sheep and cattle samples. According to
      the correlation matrix, the hook number and the hook length was negatively
      correlated. However, the correlation between the hook lengths was positive. It
      was found that the morphometric characteristics of the samples from the sheep and
      cattle closely resembled each other.

PMID- 19851964
TI  - [Should cystic echinococcosis be investigated in patients having high eosinophil
      counts?].
AB  - Cystic echinococcosis (CE) caused by the metacestode form of Echinococcus
      granulosus is one of the important health problems in Turkey and in the world. In
      this study, whether or not the presence of CE in patients with a high eosinophil
      count should be determined was investigated. A total of 946 specimens from
      patients with a high eosinophil count (>or=350/mm3) were evaluated. The age of
      patients ranged from 1-94 years. Of the patients, 392 (41.4%) were male and 554
      (58.6%), female. The specific antibody response in the specimens was determined
      by ELISA and IHA. Specific antibody response was detected in five sera of 946
      (0.53%) patients with ELISA and IHA. The patients, with an antibody response,
      were evaluated further with liver ultrasonography and chest X-ray. One patient,
      in which an antibody response was detected, had a history of renal cell carcinoma
      surgery. In one patient (0.11%), CE was detected in the liver and the diagnosis
      was confirmed by surgery. No CE was found in the other three patients. In
      conclusion, eosinophilia is not a sufficient indicator for CE alone and this
      parasite should be sought in patients with clinical and radiological signs.

PMID- 19851965
TI  - Serum leptin concentrations in patients with intestinal parasites.
AB  - Leptin is a protein hormone controlling food intake and energy expenditure. In
      all infections including parasitic infections there is loss of appetite and
      anorexia. The aim of the present study was to clarify the relationship between
      intestinal parasites and serum leptin concentrations in children and adults.
      Forty patients with intestinal parasites and 34 healthy subjects took part in
      this study. Body weight, height and body mass index (BMI) were measured for all
      patients and controls. Patients were grouped according to age and parasitic
      infections (Giardia intestinalis, Blastocystis hominis, Enterobius vermicularis,
      Entamoeba histolytica/Entamoeba dispar, Entamoeba coli). Serum leptin
      concentrations were detected by immunoenzymometric assay using the Biosource
      Leptin EASIA kit. Statistical analysis was made by Mann-Whitney-U test using SPSS
      version 10.0. In children, the serum leptin levels were not statistically
      significant (patient: 1.49+/-1.97 ng/ml, control: 3.48+/-4.97; p=0.854) But for
      adults, although the BMI of patients were similar to that of the control group;
      the leptin levels of patients were low. These levels were not significant
      (patients: 9.06+/-10.34; controls: 4.7+/-9.02 ng/ml; p=0.271). There was no
      statistical difference for leptin levels in patient groups, children and adults
      due to intestinal parasitic infections. Further investigations are needed.

PMID- 19851966
TI  - [The first report of Mulcticola hypoleucus (Denny, 1842) (Phthiraptera:
      Ischnocera) from nightjars (Caprimulgus europaeus L.) in Turkey].
AB  - In this study, two nightjars (Caprimulgus europaeus L.) were examined for
      ectoparasites. They were investigated macroscopically for lice. Then, they were
      placed into a plastic box and propoxur applied to their whole bodies. The
      ectoparasites which fell to the bottom of the box were collected and preserved in
      a vial with 70% of alcohol. No ectoparasite was observed on one nightjar while
      eleven lice specimens were collected from the other. The lice specimens were
      cleared in 10% of KOH until they were transparent. The lice were mounted on
      slides using by Canada balsam and dried in an incubater. They were examined under
      the light microscope and identified as Mulcticola hypoleucus (Denny, 1842). This
      is the first time the genus Mulcticola and the species M. hypoleucus has been
      reported from the nightjars in Turkey.

PMID- 19851967
TI  - [Investigation of the prevalence of gastrointestinal parasites in aviary birds in
      homes in the Van province].
AB  - This study was conducted to investigate the prevalence of gastrointestinal
      parasites in aviary birds in the Van province. For this purpose, fecal samples
      were collected from aviary birds (6 parrots, 5 nightingales, 24 canaries and 35
      lovebirds) in Van. In the parasitology laboratory, seventy fecal samples were
      examined using the native and sedimentation technique for helminth eggs, Eimeria
      sp. oocysts and Giardia sp. cysts. The same samples were examined by modified
      acid-fast staining for Cryptosporidium sp. oocysts. Prevalence of
      gastrointestinal parasites was found to be 8.57% (6/70) in Van. Eimeria sp.
      oocysts were detected in lovebird (8.57%) and canaries (8.33%). Cryptosporidium
      sp. oocysts were detected only in parrots (16.67%). Helminth eggs and Giardia sp.
      cysts were not found in aviary birds. However no parasites were detected in
      nightingales.

PMID- 19851968
TI  - Investigation of intestinal parasites in pig feces that are also human pathogens.
AB  - A total of 238 pig fecal specimens were collected from pig farms in Corlu
      (Tekirdag), Ayazma, and Arnavutkoy (Istanbul) during the summer. Out of the 238
      pig specimens, 105 were from pigs younger than 6 months and 133 from pigs older
      than 6 months. These were investigated for intestine parasites in particular the
      ones that are human pathogens. Cryptosporidium spp. was detected In 21 fecal
      specimens (8.8%), Giardia spp. in 9 (3.7%), Balantidium coli cysts in 4 (1.6%)
      and Ascaris suum eggs in 9 (4.1%). Giardia lamblia were found in 8 (7.6%) of 105
      pigs younger than 6 months, Cryptosporidium spp. in 12 (11.4%), Balantidium coli
      cysts in 2 (1.5%). In the pigs older than 6 months Giardia lamblia were found in
      1 (0.7%), Cryptosporidium spp. in 9 (6.7%), Balantidium coli cysts in 2 (1.5%).
      and Ascaris suum eggs in 9 (6.7%). The difference in the rate of G. lamblia
      (p=0.01) in pigs less than 6 months and of A. suum in those over 6 months was
      found to be statistically significant (p=0.005). Our results revealed that pigs
      are important sources of these parasites.

PMID- 19851969
TI  - [Sheep trichostrongylidosis in Van province].
AB  - This study was performed in the Van Municipality Slaughterhouse from January to
      December 2001. Abomasums and small intestines from a total of 104 sheep were
      transported to the parasitology laboratory of the Veterinary Faculty of Yuzuncu
      Yil University for parasitological examination. The abomasums and small
      intestines of the animals were opened with appropriate technique in the
      laboratory, and male nematodes were collected from the contents of the abomasums
      and small intestines using a sampling method, and then these parasites were
      identified. Gastrointestinal nematodes were encountered in 87.5% out of 104
      sheep. Marshallagia marshalli (85%), Teladorsagia circumcincta (75%), Nematodirus
      oiratianus (75%), N. spathiger (65%), Haemonchus contortus (40%), Tel.
      occidentalis (36%), Trichostrongylus axei (33%), N. abnormalis (19%) and T.
      probolurus (19%), Tel. davtiani (15%), Tel. trifurcate (10%), and
      Camelostrongylus mentulatus (1%) were detected. Among the parasites, the species
      encountered most often were Tel. circumcincta (45.23%) in abomasums and
      N.oiratianus (65.73%) in small intestines. The highest rate of parasites in both
      abomasums and small intestines occurred in August, September and October. It was
      found that the young animals have a parasite density higher than the adults and
      the females have parasite density higher than the males.

PMID- 19851970
TI  - [Hybrid designs in studies].
AB  - The traditional cohort and case-control designs offer a number of advantages but
      they have several important limitations. There are some alternative study designs
      for coping with limitations of conventional study designs. These studies are
      hybrid designs that are economical and efficient in studying risk factors for
      rare diseases or drug adverse reactions. Hybrid designs are increasingly commonly
      used in studies. In this paper, hybrid designs including nested case-control,
      case-cohort, case crossover and case-time control designs were presented.

PMID- 19851971
TI  - [Evaluation of cystic echinococcosis cases given a histopathologic diagnosis from
      2002 to 2007 in Diyarbakir].
AB  - Echinococcosis is a common parasitic disease manifesting as cyst formation in
      humans and animals, caused by the platyhelminth, Echinococcosis and it is an
      important health problem in our country. The aim of this study was to acquire
      knowledge about the topographic features, the prevalence of cystic echinococcosis
      and to predict its frequency in the Diyarbakir region. From 2005 to 2007, 234
      patients who had been given a histopathological diagnosis of cystic
      echinococcosis were analysed retrospectively. Based on the pathological records
      age, sex and location of the parasite were evaluated, and if a patient had the
      parasite in more than one location, it was counted as one. Female patients
      constituted 60.25% of the cases, and males, 39.74%. The average age of the
      patients was 27.01 years (28.2 years in females and 25.3 years in males). The
      most frequent location of echinococcus was in the liver (44.01%), and the second
      in the lung (31.19%). In general the characteristics of the patients correlated
      with the characteristics of previous literatures results but the age of the
      patients when diagnosed was earlier than that previously reported in the
      literature. Cystic echinococcosis was found to be an important public health
      problem in Diyarbakir region. For the eradication of echinococcosis it is
      necessary to get reliable data, and to implement an appropriate eradication
      program.

PMID- 19851972
TI  - [Case report: primary renal hydatic cyst].
AB  - Hydatic cyst is a prevalent parasitic disease in Mediterranean region, Middle
      East and Australia. Its diagnosis is sometimes problematic because of nonspecific
      complaints and unavailability of any positive result in a routine laboratory
      analysis. In this study, an primary right renal hydatic cyst which was found in a
      young female has been presented. The multilocular cyst was completely removed by
      total nephrectomia surgery. A late diagnosis due to unclear clinic manifestations
      was considered to be the main reason for the loss of the organ. It will be
      beneficial to consider a renal hydatic cyst when the patients with blurred flank
      pain are encountered.

PMID- 19851973
TI  - [Case report: Loffler's syndrome due to Ascaris lumbricoides mimicking acute
      bacterial community--acquired pneumonia].
AB  - In this study we present a patient with Loeffler's syndrome caused by Ascaris
      lumbricoides who presented with the clinical findings of community-acquired
      pneumonia (CAP). Our patient, who was twenty-five years old, and who had had
      symptoms such as coughing, expectorating, dyspnea and fever for approximately ten
      days, was hospitalized. We auscultated polyphonic rhonchuses at the both
      hemithoraxes. A chest X-ray revealed bilateral lower zone patch consolidation.
      Acute bacterial community acquired pneumonia (CAP) was diagnosed due to these
      findings and empirical antibiotic treatment was begun. Repeated sputum Gram
      stains were negative, and both sputum and blood cultures were sterile. A sputum
      smear was negative for acid-fast bacilli. The patient's fever and respiratory
      complaint did not respond to the empirical antibiotics therapy. During the course
      of advanced investigations, we measured peripheric eosinophilia, and high levels
      of total Eo and total IgE, and observed Ascaris lumbricoides eggs during stool
      examination. The patient was given a diagnosis of Loeffler's syndrome. Thereupon
      the patient was treated successfully with one dose of albendazol 400 mg. In
      conclusion, we suggest that Loeffler's syndrome must be considered early in the
      differential diagnosis for CAP when peripheric eosinophilia is seen in patients
      if they live in an endemic area for parasitic disease.

PMID- 19851974
TI  - Case report: Dermanyssus gallinae in a patient with pruritus and skin lesions.
AB  - A 40-year old woman patient who presented at the Dumlupinar University Faculty of
      Medicine Hospital reported intensified itching on her body during evening hours.
      During her physical examination, puritic dermatitis lesions were found on the
      patient's shoulders, neck and arms in particular, and systemic examination and
      laboratory tests were found to be normal. The patient's story showed that similar
      signs had been seen in other members of the household. They reside on the top
      floor of a building and pigeons are occasionally seen in the ventilation shaft.
      Examination of the house was made. The walls of the house, door architraves and
      finally beds, sheets and blankets and the windows opening to the outside were
      examined. During the examination, arthropoda smaller than 1 mm were detected.
      Following preparation of the collected samples, these were found to be
      Dermanyssus gallinae. Together with this presentation of this event, it is
      believed cutaneous reactions stemming from birds could be missed and that whether
      or not of pets or wild birds exist in or around the homes should be investigated.

PMID- 19851975
TI  - First report of Eimeria lancasterensis in a red squirrel (Sciurus vulgaris L.) in
      Turkey.
AB  - A case of coccidiosis in a young, red male squirrel (Sciurus vulgaris L.) has
      been described in this report. The squirrel was found dead and presented to the
      department of pathology for necropsy. A traumatic lesion was observed on the face
      that could have caused death. At necropsy the large and small intestines were
      swollen due to fluid and gas. During the examination of gut content numerous
      coccidia oocysts were observed. After sporulation, the oocysts were identified as
      those of Eimeria lancasterensis. In the histopathological examination numerous
      coccidia developmental stages were observed in the epithelium of small intestine.
      This is the first report of Eimeria lancasterensis identification in squirrels in
      Turkey.

PMID- 19851976
TI  - [A study on the helminth fauna linked to seasonal changes and size of the fish
      host, Leuciscus cephalus L., from Lake Dam Orenler, Afyonkarahisar].
AB  - In this study, the presence of helminths on 103 Leuciscus cephalus from the
      Orenler Dam Lake, Turkey was investigated from July 2007 to May 2008. Five
      parasite species were found in the host fish: Of these species Dactylogyrus
      vistuale was found in the gills (42.7%, 10.6+/-14.8 parasite/fish), Diplostomum
      sp. in the lens of eyes (12.6%, 4.1+/-4.0), Bothriocephalus acheilognathi in the
      intestine (23.3%, 4.8+/-10.4), Ligula intestinalis in the body cavity (12.6%,
      2.1+/-1.2), and Pomphorhynchus laevis in the intestine (32.4%,.4.6+/-5.5).
      Infection data for parasite species were determined using seasonal data and size
      distribution of the host fish.

PMID- 19851977
TI  - Observation on Monocystis constricta n. sp. (Protozoa: Apicomplexa: Monocystidae)
      from an Indian earthworm, Eutyphoeus quaripapillatus Michelsen, 1907.
AB  - A biodiversity survey of aseptate gregarines in earthworm hosts in the Calcutta
      district of West Bengal State revealed the existence of a new species of aseptate
      gregarine under the genus Monocystis Stein, 1848. The monocystid gregarines
      obtained from the earthworm host, Eutyphoeus quaripapillatus Michelsen, 1907 have
      been identified as a new species. The mucron was indistinct. The gamonts are
      elongated, ovoid, have a hood like structure at the anterior end and measure
      150.1-212.4 (188.1+/-2.1) micromx66.1-112.1 (72.3+/-1.1) microm. The gametocysts
      are ellipsoid and measure 92.3-136.3 microm (111.2+/-2.1)x78.3-114.4 microm
      (82.6+/-3.6) microm. Prominent syzygy was apparent. Oocysts are navicular,
      measuring 14.1-22.3 (18.1+/-3.2) micromx9.1-15.2 (11.9+/-1.1) microm.

PMID- 19851978
TI  - Therapeutic potential of biofilm-dispersing enzymes.
AB  - Surface-attached colonies of bacteria known as biofilms play a major role in the
      pathogenesis of medical device infections. Biofilm colonies are notorious for
      their resistance to antibiotics and host defenses, which makes most device
      infections difficult or impossible to eradicate. Bacterial cells in a biofilm are
      held together by an extracellular polymeric matrix that is synthesized by the
      bacteria themselves. Enzymes that degrade biofilm matrix polymers have been shown
      to inhibit biofilm formation, detach established biofilm colonies, and render
      biofilm cells sensitive to killing by antimicrobial agents. This review discusses
      the potential use of biofilm matrix-degrading enzymes as anti-biofilm agents for
      the treatment and prevention of device infections. Two enzymes, deoxyribonuclease
      I and the glycoside hydrolase dispersin B, will be reviewed in detail. In vitro
      and in vivo studies demonstrating the anti-biofilm activities of these two
      enzymes will be summarized, and the therapeutic potential and possible drawbacks
      of using these enzymes as clinical agents will be discussed.

PMID- 19851980
TI  - Phytochemical Analysis-the new generation.

PMID- 19851979
TI  - Suicide and fratricide in bacterial biofilms.
AB  - Bacterial autolysis has recently been identified as a key mechanism that
      regulates different phases of biofilm development including microcolony formation
      and dispersal. However such autolytic measures are limited to a subfraction of
      cells within the entire biofilm population. Here we speculate on the role biofilm
      heterogeneity plays in limiting autolysis within biofilms and further describe
      the molecular regulation of suicidal and fratricidal mechanisms in biofilm
      development of Staphylococcus aureus and Enterococcus faecalis.

PMID- 19851981
TI  - Satyajit D. Sarker to take over from Barry V. Charlwood as editor-in-chief of
      Phytochemical Analysis.

PMID- 19851982
TI  - The effects of extreme seasonality of climate and day length on the activity
      budget and diet of semi-commensal chacma baboons (Papio ursinus) in the Cape
      Peninsula of South Africa.
AB  - We examined the effects of extreme seasonality on the activity budget and diet of
      wild chacma baboons with access to a high-quality, human-derived food source. The
      Cape Peninsula of South Africa is unusual among nonhuman primate habitats due to
      its seasonal extremes in day length and climate. Winter days are markedly shorter
      and colder than summer days but have higher rainfall and higher primary
      production of annually flowering plants. This combination of fewer daylight hours
      but higher rainfall is substantially different from the ecological constraints
      faced by both equatorial baboon populations and those living in temperate
      climates with summer rainfall. We sought to understand how these seasonal
      differences affect time budgets of food-enhanced troops in comparison to both
      other food-enhanced troops and wild foraging troops at similar latitudes. Our
      results revealed significant seasonal differences in activity budget and diet, a
      finding that contrasts with other baboon populations with access to high-return
      anthropogenic foods. Similar to nonprovisioned troops at similar latitudes, troop
      members spent more time feeding, socializing, and traveling during the long
      summer days compared to the short winter days, and proportionately more time
      feeding and less time resting in summer compared to winter. Summer diets
      consisted mainly of fynbos and nonindigenous foods, whereas winter diets were
      dominated by annually flowering plants (mainly grasses) and ostrich pellets
      raided from a nearby ostrich farm. In this case, food enhancement may have
      effectively exaggerated seasonal differences in activity budgets by providing
      access to a high-return food (ostrich pellets) that was spatially and temporally
      coincident with abundant winter fallback foods (grasses). The frequent use of
      both alien vegetation and high-return, human-derived foods highlights the dietary
      flexibility of baboons as a key element of their overall success in rapidly
      transforming environments such as the South African Cape Peninsula.

PMID- 19851983
TI  - Could mindfulness decrease anger, hostility, and aggression by decreasing
      rumination?
AB  - Research suggests that rumination increases anger and aggression. Mindfulness, or
      present-focused and intentional awareness, may counteract rumination. Using
      structural equation modeling, we examined the relations between mindfulness,
      rumination, and aggression. In a pair of studies, we found a pattern of
      correlations consistent with rumination partially mediating a causal link between
      mindfulness and hostility, anger, and verbal aggression. The pattern was not
      consistent with rumination mediating the association between mindfulness and
      physical aggression. Although it is impossible with the current nonexperimental
      data to test causal mediation, these correlations support the idea that
      mindfulness could reduce rumination, which in turn could reduce aggression. These
      results suggest that longitudinal work and experimental manipulations mindfulness
      would be worthwhile approaches for further study of rumination and aggression. We
      discuss possible implications of these results.

PMID- 19851984
TI  - Genetic variation in MicroRNA genes and risk of oral premalignant lesions.
AB  - MicroRNAs (miRNAs) have been reported to play a key role in oncogenesis and,
      recently, studies have examined the role miRNAs might play in the risk of
      premalignant lesions. To our knowledge, no study has investigated the association
      between miRNA polymorphisms and risk of oral premalignant lesions (OPLs). We
      genotyped 31 single nucleotide polymorphisms (SNPs) among 21 miRNA-related genes
      in a case-control study including 136 OPL patients and 136 matched controls.
      Patients with at least one variant allele of mir26a-1:rs7372209 had a
      significantly increased risk of OPL (OR, 2.09; 95% CI, 1.23-3.56). Likewise,
      patients with at least one variant allele of DICER:rs3742330 had a significantly
      increased risk of OPL (OR, 2.09; 95% CI, 1.03-4.24). To assess the cumulative
      effects, we performed a combined unfavorable genotype analysis that included all
      SNPs showing at least a borderline statistical significance. A significant trend
      of increased risk of OPL with increasing number of unfavorable genotypes was
      observed (P for trend <0.0001). This study presents the first epidemiologic
      evidence supporting that individual as well as combined genotypes of miRNA
      related variants may be used to predict the risk of OPL, and may be useful for
      identifying patients with OPL at high risk for progression to oral cancer.

PMID- 19851985
TI  - Identification of susceptibility loci at 7q31 and 9p13 for bipolar disorder in an
      isolated population.
AB  - We performed a linkage analysis on 23 Finnish families with bipolar disorder and
      originating from the North-Eastern region of Finland, using the Illumina Linkage
      Panel IV (6K) Array with an average intermarker spacing of 0.65 cM across the
      genome. We detected genome-wide significant evidence for linkage of mood disorder
      (bipolar disorder type I, II, or not otherwise specified, manic type of
      schizoaffective psychosis, cyclothymia, or recurrent depression) to chromosomes
      7q31 (LOD = 3.20) and 9p13.1 (LOD = 4.02). Analyzing the best markers on the
      complete set of 179 Finnish bipolar families supported the findings on chromosome
      9p13 (maximum LOD score of 3.02 at position 383 Mb, immediately upstream of the
      centromere). This region harbors several interesting candidate genes, including
      contactin associated protein-like 3 (CNTNAP3) and aldehyde dehydrogenase 1
      (ALDH1B1). For the 7q31 locus, only one extended pedigree and ten families
      originating from the same late settlement region in North-Eastern Finland
      provided evidence for linkage, suggesting that a gene predisposing to bipolar
      disorder is enriched in that region. Candidate genes of interest in this locus
      include potassium-voltage-gated channel, member 2 (KCND2) and calcium-dependent
      activator protein for secretion 2 (CADPS2). The loci on the centromeric region of
      9p13 and the telomeric region of 7q31 may represent susceptibility loci for mood
      disorder in the Finnish population.

PMID- 19851986
TI  - Association of the SAT1 in/del polymorphism with suicide completion.
AB  - Several studies have observed decreased expression of spermidine/spermine N1
      acetyltransferase (SAT1) in the brains of suicide completers, and we previously
      identified a single-nucleotide polymorphism in the promoter region of SAT1 which
      was associated with suicide completion and SAT1 expression in the brain. We
      recently characterized the haplotype structure of the SAT1 promoter region and
      identified an insertion/deletion (in/del) of 15 adenine residues. This variant
      appears to be a predictor of SAT1 expression, and we were thus interested in
      determining if the lower expressing deletion allele was found more frequently
      among suicide completers. To this end, we genotyped the in/del in a sample of 771
      French-Canadian males, comprising 326 suicide completers and 445 non-suicide
      controls. We found no significant difference in the frequencies of the two
      alleles between suicide completers and controls in the entire sample. However, we
      observed a significantly higher frequency of the deletion in the depressed
      suicide completers compared to the depressed non-suicides. These results add
      support for a role of SAT1 in conferring a risk for suicide completion, in
      particular in the context of depressive disorders.

PMID- 19851987
TI  - Preventive effect of piperonyl butoxide on cyclophosphamide-induced teratogenesis
      in rats.
AB  - BACKGROUND: Cyclophosphamide induces fetal defects through metabolic activation
      by cytochrome P-450 monooxygenases (CYP). The effects of piperonyl butoxide
      (PBO), a CYP inhibitor, on the fetal development and external, visceral, and
      skeletal abnormalities induced by cyclophosphamide were investigated in rats.
      METHODS: Pregnant rats were daily administered PBO (400 mg/kg) by gavage for 7
      days (the 6th to 12th day of gestation), and intraperitoneally administered with
      cyclophosphamide (12 mg/kg) 4 h after the final treatment. On the 20th day of
      gestation, maternal and fetal abnormalities were determined by Cesarean section.
      RESULTS: Cyclophosphamide reduced fetal body weights by 30-40% without increasing
      resorption or death. In addition, it induced malformations in live fetuses: 100,
      98, and 98.2% of the external (head and limb defects), visceral
      (cerebroventricular dilatation, cleft palate, and renal pelvic/ureteric
      dilatation), and skeletal (acrania, vertebral/costal malformations, and delayed
      ossification) abnormalities, respectively. The pre-treatment of PBO greatly
      decreased mRNA expression and activity of hepatic CYP2B, which metabolizes
      cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard.
      Moreover, PBO remarkably attenuated cyclophosphamide-induced body weight loss and
      abnormalities of fetuses; score 3.57 versus 1.87 for exencephaly, 75.5% versus
      42.5% for limb defects, 65.3% versus 22% for cerebroventricular dilatation, 59.2%
      versus 5.1% for cleft palate, score 1.28 versus 0.93 for renal pelvic/ureteric
      dilatation, 71.9-82.5% versus 23-45.9% for vertebral/costal malformations, and
      84.2% versus 57.4% for delayed ossification in cyclophosphamide alone and PBO co
      administration groups. CONCLUSIONS: These results suggest that repeated treatment
      with PBO may improve cyclophosphamide-induced body weight loss and malformations
      of fetuses by down-regulating CYP2B.

PMID- 19851989
TI  - Severe embryolethality of artesunate related to pharmacokinetics following
      intravenous and intramuscular doses in pregnant rats.
AB  - Artesunate (AS), a rapid, effective, and safe antimalarial drug, has been used
      for the treatment of malaria for decades. However, severe embryolethality was
      found for injectable AS in pregnant animals. In the present study, pregnant rats
      were selected and dosed with AS (GMP product) intravenously (IV) and
      intramuscularly (IM) at varied doses daily for 13 days from gestation day (GD) 6
      to 18. In addition, a toxic dose of 1.2 mg/kg/day was subsequently tested in the
      GD 6-10, GD 11-15, and GD 16-20 periods of rat pregnancy. A pharmacokinetic study
      was also conducted to evaluate the bioavailability of AS following the IM
      administrations. Results showed that no significant adverse effects were found in
      maternal rats. All of the fetuses were either damaged or reabsorbed by placentas
      in treated pregnant rats, but doses did not show an adverse effect at 0.4 and 0.5
      mg/kg after IV and IM administrations, respectively. The survival rate of fetuses
      is dose-dependent and the 50% fetus re-absorption doses (FRD(50)) were 0.61 and
      0.60 mg/kg following the IV and IM, respectively. The most drug-sensitive period,
      showing severe embryotoxicity, was between GD 11 and 15 for injectable AS. When
      calculated with total concentrations of AS and dihydroartemisinin, an active
      metabolite of AS, the bioavailability of 97.8% after intramuscular injection was
      fulfilled to a bioequivalence of that in intravenous treatment. The fact that
      injectable AS exhibited severe embryolethality after both IV and IM injections
      seems related to their comparable pharmacokinetic profiles that indicate high
      peak concentrations in pregnant animals.

PMID- 19851988
TI  - Late-gestation ventricular myocardial reduction in fetuses of hyperglycemic CD1
      mice is associated with increased apoptosis.
AB  - BACKGROUND: Previous work in our laboratory showed reduced myocardium and dilated
      ventricular chambers in gestation day (GD) 17 hearts that were collected from
      hyperglycemic CD1 mouse dams. Pre-breeding maternal immune stimulation, using
      Freund's complete adjuvant (FCA), diminished the severity of these fetal heart
      lesions. The following experiments were performed to detect possible changes in
      fetal heart apoptotic cell death, under hyperglycemic conditions and with or
      without maternal immune stimulation. METHODS: Female CD1 mice were injected with
      200 mg/kg of streptozocin (STZ) to induce insulin-dependent diabetes mellitus.
      Half of these mice received prior FCA injection. Fetal hearts were collected on
      GD 17 and myocardial apoptotic cells were quantified using flow cytometry. A
      panel of apoptosis regulatory genes (Bcl2, p53, Casp3, Casp9, PkCe) was then
      examined in the fetal myocardium using RT-PCR. RESULTS: Early apoptotic cells and
      late apoptotic/necrotic cells were significantly increased in fetal hearts from
      STZ or STZ+FCA dams. Pre-treatment with FCA reduced late apoptotic/necrotic cells
      to control level, suggesting some cell death protection was rendered by FCA.
      Paradoxically in the face of such increased cell death, the expression of pro
      apoptotic genes Casp3 and Casp9 was decreased by diabetes, while the anti
      apoptotic gene Bcl2 was increased. CONCLUSIONS: Maternal hyperglycemia causes dys
      regulated apoptosis of fetal myocardial cells. Such effect may be prevented by
      maternal immune stimulation.

PMID- 19851991
TI  - What's in a name? Classifying 'the dropout' from treatment for anorexia nervosa.
AB  - Treatment drop-out rates for anorexia nervosa (AN) are notoriously high, and have
      remained so over the course of time, and across different treatment settings and
      modalities. The outcome for such patients is frequently poor. Despite the
      prevalence of this problem, there is little quality evidence as to why this is
      the case, and what the predictors of drop-out are. Methodological uniformity has
      been called for in order to develop a cohesive literature in this field, and this
      paper argues that we must also reflect upon how our labelling of 'the dropout'
      has shaped what we have examined to date, and how that has in turn led to a weak
      evidence base. A new, less pejorative term for those who do not complete
      treatment is needed to reflect the direction research in this area needs to take.

PMID- 19851992
TI  - Biological effects of a maternal ED on pregnancy and foetal development: a
      review.
AB  - The aim of this paper was to review the literature on the biological effects of a
      maternal eating disorder (ED) (and relevant comorbidities) in pregnancy on
      mothers and in particular on the foetus. We also aimed to highlight possible
      mechanisms of risk for long-term consequences in the offspring. Relevant
      literature was searched for using PubMed, PsychInfo and Google Scholar and
      manually through relevant research papers. The consequences of maternal EDs in
      pregnancy on EDs symptoms, psychopathology and perinatal outcomes are discussed.
      A developmental model of possible risk mechanisms for adverse long-term
      nutritional and psychopathological outcomes in the offspring is proposed.
      Maternal EDs during pregnancy are likely to have important long-term biological
      effects on the foetus. Further research needs to clarify potential biological
      risk mechanisms highlighted in this review.

PMID- 19851993
TI  - Obsessive compulsive disorder as a cause of atypical eating disorder: a case
      report.
AB  - OBJECTIVE: To describe a case of an atypical eating disorder with a diagnosis of
      obsessive-compulsive disorder and discuss the phenomenological and
      neurobiological aspects links between the disorders. CASE: a 20-year-old
      Caucasian woman presented with obsessive-compulsive disorder followed by altered
      eating habits with major weight loss and amenorrhea. The medical workup,
      treatment and outcome are described. Using cognitive-behavioural therapy,
      clomipramine and enteral nutrition, weight gain and disappearance of restrictive
      and obsessive-compulsive behaviours were obtained. CONCLUSION: Available evidence
      in the literature suggests a continuum in eating disorder and obsessive
      compulsive disorder. Our case illustrates that an obsessive-compulsive disorder
      may precede or precipitate the development of an eating disorder and highlights
      the importance of a precise differential diagnosis in eating disorders clinics.

PMID- 19851994
TI  - Comparison of body size estimation in adolescents with different types of eating
      disorders.
AB  - OBJECTIVE: To examine differences in body size estimation in adolescents with
      different types of eating disorders. METHOD: A total of 129 patients with eating
      disorders (M(age) = 16.0 +/- 1.8) and 354 healthy control participants (CP)
      (M(age) = 15.2 +/- 2.1) completed the EDI-2 and were asked to estimate the
      circumference of selected body parts by using string (BID-CA). RESULTS: CP showed
      an average overestimation of 8-16%, depending on the estimated body part. Eating
      disorder patients overestimated their body parts on average by about 30%. Thigh
      and waist estimations were the best variables for discriminating between patients
      with eating disorders and CP. No significant differences were found between
      bulimia nervosa and anorexia nervosa patients. CONCLUSIONS: Body image distortion
      plays an important role in both anorexia nervosa and bulimia nervosa. The BID-CA
      is well suited to discriminate between healthy and disordered overestimation of
      body parts.

PMID- 19851995
TI  - Animal-based welfare monitoring: using keeper ratings as an assessment tool.
AB  - Zoological institutions are in urgent need of identifying and implementing
      welfare assessment tools that allow for ongoing, quantitative monitoring of
      individual animal well-being. Although the American Zoological Association's
      (AZA) Animal Welfare Committee (AWC) promotes the use of such tools in internal
      review processes, current approaches to institutional welfare assessment are
      resource-based and outline the resources, environmental parameters and "best
      practices" recommended for promoting good welfare in a species in general. We
      highlight the value of incorporating animal-based monitoring tools that capture
      the individual animal's perspective and subjective experiences, including
      positive events and feelings, by validating zookeepers' qualitative assessments.
      We present evidence that, across a variety of species, caretakers' assessments of
      traits related to the well-being of individual animals can be both reliable and
      valid. Furthermore, we demonstrate that among researchers investigating the
      welfare of farm, laboratory, companion and even zoo animals, support already
      exists for developing and validating instruments that objectively evaluate the
      qualitative assessments of caretakers. Finally, we outline a process currently
      being evaluated at Brookfield Zoo for developing, validating and testing a cost
      effective, user-friendly monitoring tool that will help to quantify keepers'
      qualitative assessments of individual well-being and can be integrated into daily
      operations. This tool (i.e. species-specific Welfare Score Sheets designed
      through consultation with animal experts) will result in weekly scores of
      individual well-being that are expected to provide a first indicator of welfare
      issues in the collection. Specifically, scores can be reviewed during regular
      workgroup meetings to identify welfare issues proactively, to assess whether
      particular conditions, practices or events impact individual well-being, and
      finally, to evaluate the effectiveness of efforts to address welfare issues. Upon
      completion of the tool validation and testing phases, we plan to make the Welfare
      Score Sheets for our 12 study species available to other institutions, and the
      methods we applied may serve as a "blueprint" for creating similar tools for
      additional species and institutions.

PMID- 19851996
TI  - Female reproductive parameters in the Javan gibbon (Hylobates moloch).
AB  - Javan gibbons (Hylobates moloch) are one of the most endangered gibbon species in
      the world. Data on the reproductive biology of the species are almost
      nonexistent, and a general understanding of the female reproductive biology of
      this species is important for both ex situ and in situ conservation. Using 18
      years of data from 11 captive individuals, we provide new information on the
      reproductive biology of Javan gibbons based on sexual swelling and menstrual
      bleeding, including reproductive development, interbirth intervals, and ovarian
      cycle lengths. Menarche and the onset of sexual swelling occurred at 6.2 and 6.5
      years respectively, followed by a period of adolescent sterility of about 1.5
      years. Average age at first birth was 8.8 years, and interbirth intervals were
      about 2.3 years, decreasing to 1.0 year during cases of infant mortality at or
      shortly after birth. Ovarian cyclicity was measured through periods between
      menstrual bleeding and sexual swelling. Menstrual bleeding indicates the start of
      a new ovarian cycle, while sexual swelling normally occurs near the time of
      ovulation. Menstrual bleeding intervals gave a cycle length of 25.6 days, while
      sexual swelling intervals gave a cycle length of 27.3 days. These both correspond
      closely to cycle lengths in other gibbon species, as well as hormonal studies in
      Javan gibbons. In particular, observing the presence/absence of swellings was
      found to be a useful and easy method to monitor female ovarian cycles, and could
      be a practical noninvasive technique for caretakers and researchers.

PMID- 19852000
TI  - A comment on 'the impact of statins, ace inhibitors and gastric acid suppressants
      on pneumonia mortality in a UK general practice population cohort'.

PMID- 19852001
TI  - Herbal medicines during pregnancy and childhood cancers: an analysis of data from
      a pregnancy cohort study.

PMID- 19852002
TI  - Apathy is a prominent neuropsychiatric feature of radiological white-matter
      changes in patients with dementia.
AB  - OBJECTIVE: Cerebral white-matter changes (WMCs) are frequently found in dementia
      and have been proposed to be related to vascular factors and a certain
      symptomatological profile. However, few studies have included both vascular
      factors and a broad spectrum of cognitive, neurological and psychiatric symptoms,
      easily detectable by the physician in the everyday clinical work. The objective
      was to study the relationships between WMCs on MRI/CT and neuropsychiatric
      symptoms and vascular factors in patients with cognitive impairment. METHODS: One
      hundred and seventy-six patients with Alzheimer's disease, vascular dementia,
      mixed dementia, and mild cognitive impairment were included. All patients
      underwent a standardized examination including medical history, clinical
      examinations, laboratory tests and brain imaging (CT or MRI). The identification
      and severity degree of WMCs was assessed blindly to clinical findings, using a
      semi-quantitative scale. For statistical analyses, patients were grouped based on
      absence or presence of WMCs. Significant variables in bivariate analyses were
      included as predictors in stepwise multiple logistic regression analyses.
      RESULTS: Bivariate analyses showed significant associations between WMCs and age,
      gender, blood pressure, hypertension, ischaemic heart disease and TIA/RIND.
      Furthermore, there were significant associations between WMCs and apathy, mental
      slowness, disinhibition, gait disturbance and focal neurologic symptoms. The
      multivariate logistic model revealed apathy, mental slowness and age as the most
      consistent predicting factors for WMCs, together with MRI as a radiological
      method for the detection of WMCs. CONCLUSIONS: The findings indicate that WMCs in
      patients with dementia are associated with a dysexecutive-related behavioural
      symptom profile, vascular factors related to small and large vessel diseases and
      age.

PMID- 19852003
TI  - Use of film for community conservation education in primate habitat countries.
AB  - Wildlife films have become an integral part of broadcast schedules in developed
      countries. As charismatic mammals, primates are frequently the focus of the
      wildlife filmmaker's attention. Yet the people watching these films tend to be
      situated on different continents from the species concerned. Communities in
      primate habitat countries are unlikely to ever have the opportunity to gain such
      an insight into the species with which they share their environment and the
      threats these species face. Over recent years, an increasing number of filmmakers
      are realizing the importance of reaching local audiences through film for
      conservation purposes. Published research on the impact films can have on
      eliciting conservation action in developed or developing countries is minimal.
      The perceived power of wildlife films to change attitudes and behaviors is
      largely based on anecdotal evidence. This commentary highlights the on-going
      debate regarding the conservation impact of wildlife films, discusses the work of
      various NGOs that are using films for conservation purposes in habitat countries
      and makes recommendations with regards to the film type and situational context
      necessary to promote positive conservation behavior in communities. Bespoke
      conservation films convey a specific message to a specific audience at a
      particular point in time. If produced by trained local conservation educators,
      these films are likely to have the biggest impact. Films must be shown as a part
      of a conservation education program that incorporates other education materials
      and group discussion so that the desired conservation message can be clearly
      defined and reinforced. Audiences should not be made to feel disillusioned,
      depressed or vilified by the content of wildlife films. Rather films should
      increase support for conservation and empower people to act. Once enthusiasm for
      specific conservation actions has been created, practical assistance and follow
      up support is necessary to ensure ideas are implemented.

PMID- 19852004
TI  - Effects of habitat fragmentation and disturbance on howler monkeys: a review.
AB  - We examined the literature on the effects of habitat fragmentation and
      disturbance on howler monkeys (genus Alouatta) to (1) identify different threats
      that may affect howlers in fragmented landscapes; (2) review specific predictions
      developed in fragmentation theory and (3) identify the empirical evidence
      supporting these predictions. Although howlers are known for their ability to
      persist in both conserved and disturbed conditions, we found evidence that they
      are negatively affected by high levels of habitat loss, fragmentation and
      degradation. Patch size appears to be the main factor constraining populations in
      fragmented habitats, probably because patch size is positively related to food
      availability, and negatively related to anthropogenic pressures, physiological
      stress and parasite loads. Patch isolation is not a strong predictor of either
      patch occupancy or population size in howlers, a result that may be related to
      the ability of howlers to move among forest patches. Thus, we propose that it is
      probable that habitat loss has larger consistent negative effects on howler
      populations than habitat fragmentation per se. In general, food availability
      decreases with patch size, not only due to habitat loss, but also because the
      density of big trees, plant species richness and howlers' home range size are
      lower in smaller patches, where howlers' population densities are commonly
      higher. However, it is unclear which vegetation attributes have the biggest
      influence on howler populations. Similarly, our knowledge is still limited
      concerning the effects of postfragmentation threats (e.g. hunting and logging) on
      howlers living in forest patches, and how several endogenous threats (e.g.
      genetic diversity, physiological stress, and parasitism) affect the distribution,
      population structure and persistence of howlers. More long-term studies with
      comparable methods are necessary to quantify some of the patterns discussed in
      this review, and determine through meta-analyses whether there are significant
      inter-specific differences in species' responses to habitat loss and
      fragmentation.

PMID- 19852005
TI  - Density estimates of Panamanian owl monkeys (Aotus zonalis) in three habitat
      types.
AB  - The resolution of the ambiguity surrounding the taxonomy of Aotus means data on
      newly classified species are urgently needed for conservation efforts. We
      conducted a study on the Panamanian owl monkey (Aotus zonalis) between May and
      July 2008 at three localities in Chagres National Park, located east of the
      Panama Canal, using the line transect method to quantify abundance and
      distribution. Vegetation surveys were also conducted to provide a baseline
      quantification of the three habitat types. We observed 33 individuals within 16
      groups in two out of the three sites. Population density was highest in Campo
      Chagres with 19.7 individuals/km(2) and intermediate densities of 14.3
      individuals/km(2) were observed at Cerro Azul. In la Llana A. zonalis was not
      found to be present. The presence of A. zonalis in Chagres National Park, albeit
      at seemingly low abundance, is encouraging. A longer-term study will be necessary
      to validate the further abundance estimates gained in this pilot study in order
      to make conservation policy decisions.

PMID- 19852006
TI  - Differential expression of PCA3 and BMCC1 in prostate cancer.

PMID- 19852009
TI  - Double group transfer reactions: role of activation strain and aromaticity in
      reaction barriers.
AB  - Double group transfer (DGT) reactions, such as the bimolecular automerization of
      ethane plus ethene, are known to have high reaction barriers despite the fact
      that their cyclic transition states have a pronounced in-plane aromatic
      character, as indicated by NMR spectroscopic parameters. To arrive at a way of
      understanding this somewhat paradoxical and incompletely understood phenomenon of
      high-energy aromatic transition states, we have explored six archetypal DGT
      reactions using density functional theory (DFT) at the OLYP/TZ2P level. The main
      trends in reactivity are rationalized using the activation strain model of
      chemical reactivity. In this model, the shape of the reaction profile
      DeltaE(zeta) and the height of the overall reaction barrier DeltaE( not
      equal)=DeltaE(zeta=zeta(TS)) is interpreted in terms of the strain energy
      DeltaE(strain)(zeta) associated with deforming the reactants along the reaction
      coordinate zeta plus the interaction energy DeltaE(int)(zeta) between these
      deformed reactants: DeltaE(zeta)=DeltaE(strain)(zeta)+DeltaE(int)(zeta). We also
      use an alternative fragmentation and a valence bond model for analyzing the
      character of the transition states.

PMID- 19852008
TI  - Depression and parkinsonism in older Europeans: results from the EURODEP
      concerted action.
AB  - OBJECTIVE: The prevalence rate of depression among patients with Parkinson's
      disease (PD) has been estimated at 25%, although prevalence figures range between
      7-76%. Relatively few studies on PD and depression are based on random samples in
      the general population. Some depressive symptoms can also be understood as
      symptoms of parkinsonism, and the current study aims to describe which 'overlap'
      symptoms can be identified in a community sample. METHODS: Data are employed from
      the EURODEP collaboration. Nine study centres, from eight western European
      countries, provided data on depression (most GMS-AGECAT), depressive symptoms
      (EURO-D items and anxiety), parkinsonism (self-report of PD or clinical signs of
      PD), functional disability and dementia diagnosis. RESULTS: Data were complete
      for 16 313 respondents, aged 65 and older; 306 (1.9%) reported or had signs of
      parkinsonism. The rate of depression was about twice as high among respondents
      with parkinsonism (unadjusted Odds Ratio 2.44, 95% Confidence Interval 1.88
      3.17), also among those without functional disability. 'Overlap' symptoms between
      parkinsonism and depression, were represented by motivation and concentration
      problems, appetite problems and especially the symptom of fatigue (energy loss).
      However, principal component analysis showed that these 'overlap' symptoms loaded
      on different factors of the EURO-D scale. CONCLUSIONS: As among clinical patients
      with PD, depression is highly common in community dwelling older people with
      parkinsonism, even among those without functional disability. Although fatigue
      did not strongly relate to motivational symptoms, both types of 'overlap'
      symptoms possibly trigger a final common pathway towards a full depressive
      syndrome.

PMID- 19852010
TI  - Mechanistic studies on the reaction between R2N-NONOates and aquacobalamin:
      evidence for direct transfer of a nitroxyl group from R2N-NONOates to cobalt(III)
      centers.

PMID- 19852011
TI  - Ion-molecule reactions in helium nanodroplets doped with C60 and water clusters.

PMID- 19852012
TI  - A rigid helical peptide axle for a [2]rotaxane molecular machine.

PMID- 19852013
TI  - Chivosazoles A and F, cytostatic macrolides from myxobacteria, interfere with
      actin.
AB  - Chivosazoles A and F, isolated from Sorangium cellulosum, showed high
      antiproliferative activity with different mammalian cell lines including human
      cancer cells. The chivosazoles caused a delay in G2/M phase of the cell cycle,
      and treated cells often contained two nuclei. By labeling F-actin it was shown
      that the actin cytoskeleton of the cells starts to break down after a few minutes
      of treatment. In vitro polymerization assays with purified G-actin revealed that
      the chivosazoles inhibit actin polymerization and also cause a depolymerization
      of pyrene-labeled F-actin microfilaments prepared in vitro. Chivosazoles are new
      tools for the investigation of issues concerning the actin cytoskeleton and they
      have a different mode of action from the known microfilament-disrupting compounds
      like rhizopodin and cytochalasin D.

PMID- 19852014
TI  - Theoretical study on hydrogen-bond effects in IR spectra of high- and low
      temperature phases of nitric acid dihydrate.
AB  - The low- and high-temperature phases (alpha and beta, respectively) of solid
      nitric acid dihydrate (NAD) are studied in depth by DFT methods. Each phase
      contains two types of complex structures (H(3)O(+)) x (H(2)O), designated A and
      B, with different hydrogen-bonding (HB) characteristics. The theoretical study
      reveals that type A complexes are weakly bound and could be described as
      (H(3)O)(+) and H(2)O aggregates, with decoupled vibrational modes, whereas in
      type B structures the proton is situated close to the centre of the O...O bond
      and induces strong vibrational coupling. The proton-transfer mode is predicted at
      quite different wavenumbers in each complex, which provides an important
      differentiating spectral feature, together with splitting of some bands in beta
      NAD. Theoretical spectra are estimated by using two GGA parameterizations,
      namely, PBE and BLYP. The potential-energy surface for each type of HB in NAD is
      also studied, as is the spectral influence of displacement of the shared H atom
      along the O-O bond. The results are compared to literature infrared spectra
      recorded by different techniques, namely, transmission and reflection-absorption,
      with both normal and tilted incident radiation. This work provides a thorough
      assignment of the observed spectra, and predictions for some spectra not yet
      available. The usefulness of high-level theoretical calculations as performed
      herein to discriminate between two phases of a solid crystal is thus evidenced.

PMID- 19852015
TI  - Optical fiber/nanowire hybrid structures for efficient three-dimensional dye
      sensitized solar cells.

PMID- 19852016
TI  - Fast prediction of cytochrome P450 mediated drug metabolism.
AB  - Cytochrome P450 mediated metabolism of drugs is one of the major determinants of
      their kinetic profile, and prediction of this metabolism is therefore highly
      relevant during the drug discovery and development process. A new rule-based
      method, based on results from density functional theory calculations, for
      predicting activation energies for aliphatic and aromatic oxidations by
      cytochromes P450 is developed and compared with several other methods. Although
      the applicability of the method is currently limited to a subset of P450
      reactions, these reactions describe more than 90 % of the metabolites. The rules
      employed are relatively few and general, and when combined with solvent
      accessible surface area calculations to account for steric accessibility, the
      method gives a major P450 metabolite as first-ranked position for 75 % of the
      substrates, and ranked in the top three for 90 % of substrates for a set of 20
      substrates. In combination with docking, it can predict isoform-specific
      metabolism, and we apply this on CYP1A2 with very good results on 81 substrates,
      for which we find a major metabolite ranked in the top three for 90 % of the
      substrates (100 % in the training set and 87 % in the larger test set).

PMID- 19852017
TI  - Occupational obstructive airway diseases caused by the natural gas odorant
      tetrahydrothiophene--two case reports.
AB  - BACKGROUND: Tetrahydrothiophene (THT) is frequently used to odorize natural
      (city) gas. Only sparse data on adverse health effects of THT on humans are
      available. METHODS: We performed a literature search and clinical investigations
      including case history and cardiopulmonary diagnostic tests in two symptomatic
      THT-exposed outpatients. RESULTS: The two THT-exposed city workers developed
      transient neurologic symptoms such as nausea, vomiting, headaches, as well as
      skin and mucosa irritation, chronic rhinitis, chronic obstructive pulmonary
      disease, arterial hypertension, and cardiac arrhythmia. The neurological symptoms
      and respiratory disorders were found to be caused by intermittently high THT
      exposures. In favor of a causal relationship were severe work-related
      neurological and respiratory symptoms in previously healthy workers, results of
      animal experiments, and another report with very similar findings in the
      literature. The etiology of arterial hypertension and cardiac arrhythmia,
      however, remains unclear. CONCLUSIONS: Our two case reports demonstrate that
      repeated high THT-exposures can--in addition to neurotoxic symptoms--elicit
      chronic obstructive pulmonary disease. We recommend improved primary and
      secondary preventive measures, including the establishment of a TLV.

PMID- 19852018
TI  - Occupational injuries among aides and nurses in acute care.
AB  - BACKGROUND: Occupational injuries are common among nursing personnel. Most
      epidemiologic research on nursing aides comes from long-term care settings.
      Reports from acute care settings often combine data on nurses and aides even
      though their job requirements and personal characteristics are quite different.
      Our objective was to assess risk of work-related injuries in an acute care
      setting while contrasting injuries of aides and nurses. METHODS: A retrospective
      cohort of aides (n = 1,689) and nurses (n = 5,082) working in acute care at a
      large healthcare system between 1997 and 2004 were identified via personnel
      records. Workers' compensation filings were used to ascertain occupational
      injuries. Poisson regression was used to estimate rate ratios (RR) and 95%
      confidence intervals (95% CI). RESULTS: Aides had higher overall injury rates
      than nurses for no-lost work time (RR = 1.2, 95% CI: 1.1-1.3) and lost work time
      (RR = 2.8, 95% CI: 2.1-3.8) injuries. The risk of an injury due to lifting was
      greater among aides compared to nurses for both non-lost work time and lost work
      time injuries. Injury rates among aides were particularly high in rehabilitation
      and orthopedics units. Most of the injuries requiring time away from work for
      both groups were related to the process of delivering direct patient care.
      CONCLUSIONS: Our findings illustrate the importance of evaluating work-related
      injuries separately for aides and nurses, given differences in injury risk
      profiles and injury outcomes. It is particularly important that occupational
      safety needs of aides be addressed as this occupation experiences significant job
      growth.

PMID- 19852019
TI  - Excessive longitudinal FEV1 decline and risks to future health: a case-control
      study.
AB  - BACKGROUND: Accelerated loss of forced expiratory volume in 1 s (FEV(1)) in an
      individual is considered an indicator of developing lung disease. METHODS: We
      investigated longitudinal FEV(1) slopes, calculated by simple linear regression,
      and adverse health outcomes after 10-30 years, among 1,428 chemical plant
      workers. Cases were defined by FEV(1) slopes below 5th percentile values for the
      cohort. Cases were matched with controls (107 pairs) for race, gender, smoking
      status, year of birth, age, height, and calendar year at first test. Matched pair
      statistics were used for comparisons. RESULTS: Cases had a higher proportion,
      compared to controls, of diagnosis of COPD or emphysema (17.8% vs. 1.9%, P =
      0.0002), medication use for respiratory diseases (24.3% vs. 4.7%, P < 0.0001),
      dyspnea (15% vs. 3.7%, P = 0.0042), and wheezing or rhonchi on examination (10.3%
      vs. 1.9%, P = 0.0225). CONCLUSIONS: Chemical plant workers who experienced
      accelerated FEV(1) declines experienced four to nine times as many adverse health
      conditions over 10-30 years.

PMID- 19852020
TI  - Assessing the contribution of working conditions to socioeconomic disparities in
      health: a commentary.
AB  - INTRODUCTION: Occupational health researchers can play a pivotal role in
      increasing our understanding of the role of physical and psychosocial working
      conditions in producing socioeconomic health disparities and trends of increasing
      socioeconomic health disparities, contributing to interventions to reduce such
      disparities, and helping to improve public education materials on this subject.
      However, a number of methodological challenges in this field need to be
      considered. METHODS: Commentary, including a review of selected studies.
      RESULTS/CONCLUSION: Research needs to be guided by models of the associations
      between social (socioeconomic position (SEP), race/ethnicity, immigration status,
      and gender) and occupational variables and health, to avoid inappropriate control
      for confounding, and to specify causal pathways (mediation) and interaction
      effects. Different approaches to the theory and measurement of SEP also need to
      be tested.

PMID- 19852022
TI  - Transgene expression of transfected supercoiled plasmid DNA concatemers in
      mammalian cells.

PMID- 19852024
TI  - Methods of elderly suicides in England and Wales by country of birth groupings.

PMID- 19852026
TI  - Sporadic late onset nemaline myopathy responsive to IVIg and immunotherapy.
AB  - Sporadic late onset nemaline myopathy (SLONM) is a progressive myopathy of
      indeterminate etiology and poor outcome. If associated with a monoclonal
      gammopathy, SLONM carries a more unfavorable prognosis. Immunotherapy was
      unsuccessful. We report two HIV-negative SLONM/monoclonal gammopathy patients who
      improved following intravenous immunoglobulin (IVIg) treatment alone or in
      combination with immunosuppressant agents. This favorable response to treatment
      suggests that a dysimmune mechanism is operative in some SLONM individuals. We
      suggest that IVIg deserves initial consideration for SLONM therapy.

PMID- 19852027
TI  - Rituximab in the management of refractory myasthenia gravis.
AB  - Myasthenia gravis (MG) is an immune-mediated disorder with a variable response to
      treatment. In this study, patients with refractory MG who were treated with
      rituximab were identified. A review of patients referred to the Yale
      Neuromuscular Clinic was performed. Patients with refractory MG who were treated
      with rituximab were reviewed for response to treatment. Patients who had muscle
      specific kinase (MuSK(+)) or acetylcholine receptor (AChR(+)) antibodies were
      included. Six patients were identified who met the criteria described. All
      patients tolerated rituximab without side effects and had a reduced need for
      immunosuppressants and/or improvement in clinical function. Patients with
      refractory MG appeared to respond to rituximab in this small, retrospective
      study. This result suggests that a larger, prospective trial is indicated.

PMID- 19852030
TI  - Racial disparities for uterine corpus tumors: changes in clinical characteristics
      and treatment over time.

PMID- 19852031
TI  - Inflammatory myofibroblastic tumors in childhood: a report from the Italian
      Cooperative Group studies.
AB  - BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are myofibroblastic
      lesions with unpredictable biologic behavior that occur at a young age. For this
      report, the authors investigated clinicopathologic features in a series of
      pediatric IMTs. The objective of the study was to identify morphologic or
      immunohistochemical prognostic markers and the possible pathogenic role of human
      herpes virus 8 (HHV-8). METHODS: Twenty-six patients were observed over a period
      of 18 years. Clinical/histologic data were reviewed, and
      immunohistochemical/molecular studies were performed. RESULTS: Patients ages 8
      216 months (median age, 60 months) presented with tumors of the lung-bronchus (8
      patients), abdomen (17 patients), and thoracic wall (1 patient). Twenty-one
      patients underwent complete excision, and microscopic or macroscopic residual
      disease was present in 5 of those patients. Chemotherapy was received by 5
      patients. After a median follow-up of 6.6 years, 24 patients were in complete
      remission, and 2 patients had died of disease. Local recurrences were observed in
      6 patients (including 4 recurrences that occurred after a complete excision).
      Cytologic atypia, low inflammatory infiltrate, and a rich myxoid pattern were
      detected in patients who had recurrent disease or a poor prognosis. Anaplastic
      lymphoma kinase (ALK) was positive in 7 patients (including 2 patients with
      recurrent disease). No correlation between clusterin expression and prognosis was
      demonstrated. HHV-8 was identified in 1 pulmonary IMT. CONCLUSIONS: IMTs are
      locally aggressive lesions. In this series, the local recurrence rate was 23%,
      and the 5-year and 10-year event-free survival rates were 87.4% and 72.8%,
      respectively. The results indicated that the treatment of choice is a complete,
      nonmutilating excision; chemotherapy may be given to patients who have
      microscopic or macroscopic residual disease, although the results are
      controversial; cytologic atypia and positive ALK status are more frequent in
      aggressive tumors, whereas metastatic tumors are negative for ALK; and HHV8 is
      not involved in the pathogenesis of IMT.

PMID- 19852032
TI  - Topographical short-term memory differentiates Alzheimer's disease from
      frontotemporal lobar degeneration.
AB  - We used a recently developed test of spatial memory--the Four Mountains Test--to
      investigate the core cognitive processes underpinning topographical
      disorientation in patients with amnestic mild cognitive impairment (a-MCI) and
      mild Alzheimer's disease (AD). Performance of these clinical groups was compared
      with age-matched controls, patients with frontotemporal lobar degeneration
      (FTLD), and patients with subjective memory impairments. We investigated the
      perception (concurrent match-to-sample) and short-term retention (2-s delayed
      match-to-sample) of the configuration of topographical features in computer
      generated landscapes shown from different viewpoints. Thirty-one patients were
      tested (7 AD, 6 a-MCI, 7 temporal variant FTLD, 5 frontal variant FTLD, 6
      subjective memory impairment) and 25 age- and gender-matched controls. Brain MRI
      was available for 27 patients; medial temporal lobe atrophy was assessed using a
      visual rating scale. Patients with a-MCI or mild AD were impaired on
      topographical short-term memory, but not perception. No other group differences
      were found on the topographical subtests. Notably, patients with temporal
      variants of FTLD performed normally, regardless of the laterality of damage.
      Subtests for the perception and retention of nonspatial aspects of the landscapes
      (weather conditions, seasonal and daily variations in lighting and color) were
      poor at differentiating the patient groups. These results indicate a core deficit
      in representing topographical layout, even for very short durations, within the
      context of more general long-term memory impairments found in AD, and suggest
      that this function is particularly sensitive to the earliest stages of the
      disease.

PMID- 19852033
TI  - Prognostic value of symptom burden for overall survival in patients receiving
      chemotherapy for advanced nonsmall cell lung cancer.
AB  - BACKGROUND: Patient-reported outcomes have shown independent prognostic value for
      patients with nonsmall cell lung cancer (NSCLC). However, translating patient
      reported outcomes into useful prognostic information for individual patients has
      been problematic. METHODS: A total of 94 patients with advanced NSCLC and an
      Eastern Cooperative Oncology Group performance status (PS) of 0 to 2 who
      qualified for chemotherapy rated symptom severity using the M. D. Anderson
      Symptom Inventory before and after their first chemotherapy cycle. Prognostic
      values of baseline symptoms and changes in symptom severity were examined by Cox
      proportional hazards models. RESULTS: In multivariate analysis, controlled for
      demographic and other factors, baseline coughing rated > or =4 independently
      predicted significantly higher risk for shorter survival (hazards ratio [HR],
      8.69; P < .0001). Patients with coughing > or =4 and a PS of 2 were more likely
      to have shorter survival (HR, 20.6; P < .0001) than patients with coughing <4 and
      a PS of 0 to 1. A 1-point or greater increase in severity of fatigue (P < .05),
      shortness of breath, or poor appetite (P < .01) from baseline to the end of the
      first chemotherapy cycle was also found to be independently associated with
      higher risk for poor survival. CONCLUSIONS: An increased risk for shorter
      survival was indicated by moderate to severe coughing at baseline or by increased
      fatigue or shortness of breath during the first chemotherapy cycle in patients
      with advanced NSCLC. Although cross-validation is needed, these data suggest that
      an individual patient's symptom severity scores, quickly obtainable in the
      clinic, might contribute clinically useful information for treatment planning for
      that patient. Society.

PMID- 19852034
TI  - Premalignant and malignant cells in sputum from lung cancer patients.
AB  - BACKGROUND: The objective of this study was to assess the frequency of
      premalignant and malignant cells in sputum from patients with lung cancer and to
      measure the dependence of these cells on cancer stage, histologic type, tumor
      size, and tumor location. METHODS: This analysis included 444 patients with lung
      cancer. First, all patients were asked to produce sputum spontaneously; then,
      they underwent sputum induction. Slide preparations of the sputa were screened
      for the presence of abnormal cells. RESULTS: Of all patients with lung cancer who
      had produced adequate specimens, 74.6% had sputum that was positive for
      premalignant or worse cells, whereas 48.7% had sputum that was positive for
      malignant cells alone. Surprisingly, the presence of premalignant or worse cells
      in sputum depended only moderately on disease stage (82.9% of stage IV cancers vs
      65.9% of stage I cancers), tumor size (78.6% of tumors >2 cm vs 64.7% of tumors
      <or=2 cm), and location (83.3% of central lesions vs 68% of peripheral lesions)
      and was found to be independent of histologic tumor type (78.4% of squamous cell
      carcinomas vs 71.5% of adenocarcinomas, 74.5% of small cell carcinomas, and 75%
      of large cell carcinomas). CONCLUSIONS: The findings of the current study
      suggested the important potential of sputum cytology for lung cancer detection
      and risk assessment across all stages, histologic types, tumor sizes, and
      locations. However, the high sensitivities in this study were achieved with a
      level of scrutiny not feasible in the laboratory routine. The diagnostic
      potential of sputum cytology may be exploited better through the standardization
      and automation of sputum preparation and analysis.

PMID- 19852035
TI  - A further investigation on a MALDI-based method for evaluation of markers of
      renal damage.
AB  - The validity of the urinary protein profile to characterize the pathological
      states of diabetic, nephropathic and diabetic-nephropathic patients was
      considered on the basis of previously obtained results by MALDI/MS, showing a
      different abundance ratio of the collagen alpha1 and alpha5 chain precursor
      fragments at m/z 1219 and 2049 and of the uromodulin precursor fragment at m/z
      1912 observed in healthy subjects and patients; a larger number of subjects was
      examined and the obtained results were statistically evaluated. The p values
      related to the observed differences indicate that they are statistically
      significant when comparing all patients versus healthy controls, diabetic with
      normo or microalbuminuria versus nephropathic with advanced renal disease
      patients and diabetic with normo or microalbuminuria versus diabetic with
      advanced nephropathy patients. The scatter plot matrix gives evidence of the
      strict inverse relationship between the abundances of ions at m/z 1912 and 1219,
      the correlation coefficient being particularly high (r = 0.921, p < 0.001). The
      relationship between the true positive rate (sensitivity) and false positive rate
      (1-specificity) for every possible cutoff value in abundance of the considered
      ionic species was investigated through the receiver-operating characteristic
      (ROC) curve. The obtained data indicate that a good differentiation of
      nephropathic patients with advanced renal disease and diabetic patients with
      advanced nephropathy versus healthy subjects can be easily obtained by this
      approach.

PMID- 19852036
TI  - The Journal of Pathology 2008 Jeremy Jass Prize for Research Excellence in
      Pathology.
AB  - The first Jass Prize for Research Excellence has been awarded to a group from
      Hannover in Germany. These authors discovered the epigenetic inactivation of
      microRNA gene hsa-mir-9-1 in human breast cancer and characterized its biological
      and clinical relevance. This frequent epigenetic silencing was found to occur
      early in the development of breast cancer, and illustrates another mechanism by
      which tumour development is influenced by genes that operate without expression
      as proteins.

PMID- 19852037
TI  - Significance of protein binding in pharmacokinetics and pharmacodynamics.
AB  - The significance of plasma protein binding on drug efficacy and, subsequently,
      the clinical relevance of changes in protein binding has been controversially
      discussed for decades. The uncertainty concerning the impact of plasma protein
      binding on a drug's pharmacological activity is, in part, related to the approach
      used when investigating and interpreting protein binding effects in vitro and in
      vivo. Frequently, a generalized one-size-fits-all approach, such as "protein
      binding does matter/does not matter," may not be applicable. An appropriate
      analysis requires careful consideration of both pharmacokinetic and
      pharmacodynamic processes, as they both contribute to the safety and efficacy of
      drugs. Therefore, the aim of this article is to provide a concise review of the
      theoretical concepts of protein binding, and to discuss relevant examples where
      applicable.

PMID- 19852038
TI  - Nuchal translucency screening in monochorionic twin pregnancies.

PMID- 19852039
TI  - MRgFUS: a sound approach to fibroid therapy.

PMID- 19852040
TI  - Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis
      C pegylated interferon and ribavirin nonresponders.
AB  - Merimepodib (MMPD) is an orally administered, inosine monophosphate dehydrogenase
      inhibitor that has shown antiviral activity in nonresponders with chronic
      hepatitis C (CHC) when combined with pegylated interferon alfa 2a (Peg-IFN-alfa
      2a) and ribavirin (RBV). We conducted a randomized, double-blind, multicenter,
      phase 2b study to evaluate the antiviral activity, safety, and tolerability of
      MMPD in combination with Peg-IFN-alfa-2a and RBV in patients with genotype 1 CHC
      who were nonresponders to prior therapy with Peg-IFN and RBV. Patients received
      50 mg MMPD, 100 mg MMPD, or placebo every 12 hours, in addition to Peg-IFN-alfa
      2a and RBV, for 24 weeks. Patients with a 2-log or more decrease from baseline or
      undetectable hepatitis C virus (HCV) RNA levels at week 24 were then eligible to
      continue Peg-IFN-alfa-2a and RBV for a further 24 weeks, followed by 24 weeks of
      follow-up. The primary efficacy endpoint was sustained virological response (SVR)
      rate at week 72 in all randomized patients who received at least one dose of
      study drug and had a history of nonresponse to standard therapy. A total of 354
      patients were randomized to treatment (117 to placebo; 119 to 50 mg MMPD; 118 to
      100 mg MMPD), and 286 completed the core study. The proportion of patients who
      achieved SVR was similar among the treatment groups: 6% (6/107) for 50 mg MMPD,
      4% (5/112) for 100 mg MMPD, and 5% (5/104) for placebo (P = 0.8431). Adverse
      event profiles for the MMPD combination groups were similar to that for Peg-IFN
      alfa and RBV alone. Nausea, arthralgia, cough, dyspnea, neutropenia, and anemia
      were more common in patients taking MMPD. CONCLUSION: The addition of MMPD to Peg
      IFN-alfa-2a and RBV combination therapy did not increase the proportion of
      nonresponder patients with genotype 1 CHC achieving an SVR.

PMID- 19852041
TI  - Clinical outcomes of magnetic resonance-guided focused ultrasound surgery for
      uterine myomas: 24-month follow-up.
AB  - OBJECTIVES: To assess the volume reduction ratio, symptom improvement and
      reintervention rate following magnetic resonance-guided focused ultrasound
      surgery (MRgFUS) for uterine myomas. METHODS: A total of 91 Japanese women with
      symptomatic myomas underwent MRgFUS between June 2004 and June 2008 using the
      ExAblate 2000 system. The volume change ratio was calculated at 6, 12 and 24
      months following MRgFUS based on T2-weighted magnetic resonance images. The
      symptom severity score (SSS) was examined before and after the treatment (at 3,
      6, 12 and 24 months). Additional post-MRgFUS treatments, such as hysterectomy,
      myomectomy, uterine artery embolization or repeat MRgFUS, were recorded and the
      reinterventional treatment rates were compared according to the signal intensity
      of pretreatment T2-weighted magnetic resonance images of the myomas. RESULTS: The
      mean volume change ratios of low- and intermediate-intensity (Type 1/2) myomas
      were -36.5% 6 months post-procedure and -39.5% 24 months post-procedure. The mean
      +/- SD SSS value for patients with Type 1/2 myomas before MRgFUS was 35.1 +/-
      21.0, and the values diminished significantly during the 24-month follow-up
      period to a mean value of around 15.0. High-intensity (Type 3) myomas were not
      observed to have decreased in size 6 months after MRgFUS. Of the 45 Type 1/2
      myoma patients with complete follow-up, seven required reinterventional treatment
      within 24 months. The reintervention rates were 14.0% for Type 1/2 patients and
      21.6% for Type 3 patients at 24 months post-treatment. CONCLUSIONS: Moderate
      volume reductions of Type 1/2 myomas were noted following MRgFUS, and the
      reduction in SSS values and the relatively low reintervention rates observed are
      encouraging. We found MRgFUS to be an appropriate treatment method for Type 1/2
      uterine myomas.

PMID- 19852042
TI  - Non-invasive magnetic resonance-guided focused ultrasound treatment of uterine
      fibroids in a large Japanese population: impact of the learning curve on patient
      outcome.
AB  - OBJECTIVES: To describe the learning curve effect of magnetic resonance-guided
      focused ultrasound surgery (MRgFUS) on the outcomes of patients treated for
      uterine fibroids in four centers in Japan. METHODS: The extent of fibroid
      ablation (often used to measure treatment success) was evaluated using the non
      perfused volume (NPV) ratio in 287 Japanese patients. The patients were divided
      into two equal groups according to the chronological treatment time and results
      were compared between these groups to estimate the learning curve effect. Results
      were also compared with published data from clinical trials. RESULTS: The NPV
      ratio increased chronologically, from 39.3% to 54.0% (P < 0.001), indicating
      increasing effectiveness of the treatment with experience. The mean NPV ratios
      for the entire patient population were over double that of previous clinical
      trials (46.6% vs. 21.9%; P < 0.001). No serious complications were reported.
      CONCLUSION: The learning process and accumulation of data on MRgFUS enable the
      optimization of treatments in order to safely achieve large NPV ratios and
      sustained clinical benefit.

PMID- 19852043
TI  - Automated sonographic tubal patency evaluation with three-dimensional coded
      contrast imaging (CCI) during hysterosalpingo-contrast sonography (HyCoSy).

PMID- 19852044
TI  - Feasibility of focused ultrasound therapy for recurrent cervicitis with high-risk
      human papillomavirus infection.
AB  - OBJECTIVE: To investigate the feasibility of focused ultrasound therapy for
      recurrent cervicitis with high-risk human papillomavirus (HR-HPV) infection.
      METHODS: This was a prospective clinical study, in which 20 patients with HR-HPV
      positive recurrent cervicitis were enrolled. Focused ultrasound therapy was
      performed by one gynecologist. All patients were followed up for 6 months after
      ultrasound therapy. Telephone interviews, colposcopic examinations and Hybrid
      Capture II tests were performed to assess the safety and effectiveness of focused
      ultrasound therapy for HR-HPV-positive cervicitis. RESULTS: Ultrasound therapy
      was tolerated well, and no severe complications were observed in any patient.
      Vaginal discharge was found intermittently in 95% of patients. Without any
      intervention this disappeared 1 month after ultrasound therapy. Patients'
      symptoms were relieved significantly by ultrasound therapy, including 88.9%
      patients who had abundant leukorrhea, 80% who had pelvic pain and 87.5% who had
      postcoital bleeding. No colposcopic evidence of cervicitis remained
      postoperatively in 75% of patients, and cytological examination showed that the
      lesions had disappeared in 80% of patients. Follow-up HPV testing revealed that
      75% of patients presented negative HR-HPV infection following treatment.
      CONCLUSIONS: Focused ultrasound therapy is feasible and effective in the
      treatment of patients with HR-HPV-positive cervicitis. It may provide a useful
      non-invasive treatment for recurrent cervicitis with HR-HPV infection.

PMID- 19852045
TI  - Nasal bone length in trisomy 18, triploidy and Turner syndrome analyzed on
      postmortem radiographs.

PMID- 19852047
TI  - Reference intervals of gestational sac, yolk sac and embryo volumes using three
      dimensional ultrasound.
AB  - OBJECTIVES: To create reference intervals of gestational sac volume (GSV), yolk
      sac volume (YSV), embryo volume (EV), crown-rump length (CRL) and gestational sac
      diameter (GSD) in the first trimester of pregnancy using three-dimensional
      ultrasound. METHODS: Women in the first trimester of pregnancy were invited to
      participate in the study. Inclusion criteria were well-established dates, and
      that the women were non-smokers and healthy, without any medical disorders. Three
      dimensional ultrasound volumetric data (GSV, YSV, EV) were collected together
      with standard two-dimensional measurements of CRL and GSD. For each measurement
      separate regression models were fitted to estimate the mean and SD at each
      gestational age. The 5(th), 50(th) and 95(th) centiles were derived using a
      combination of these regression models. RESULTS: One hundred and sixty-six women
      at between 6 and 12 weeks' gestation were scanned once. The mean ( +/- SD)
      maternal age was 29.4 ( +/- 5) years. There were no miscarriages and no
      congenital abnormalities were noted. Mean gestational age at delivery was 39.3 (
      +/- 1.4) weeks and mean birth weight was 3.3 ( +/- 0.4) kg. The CRL centiles
      fitted a cubic model and the GSD centiles fitted a linear model. The centiles for
      YSV fitted a quadratic model on the modified log-transformed data. The centiles
      for GSV and EV were modeled using quantile regression. CONCLUSION: Reference
      intervals and centile charts for first-trimester GSV, YSV and EV have been
      created in addition to CRL and GSD using rigorous methodology.

PMID- 19852046
TI  - Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal
      hysterectomy for treatment of uterine leiomyomas.
AB  - OBJECTIVES: To compare women undergoing magnetic resonance-guided focused
      ultrasound (MRgFUS) to a group of contemporaneously recruited women undergoing
      total abdominal hysterectomy. Patient demographics, safety parameters, quality of
      life outcomes and disability measures are reported. METHODS: One hundred and nine
      women were recruited in seven centers for MRgFUS treatment and 83 women who
      underwent abdominal hysterectomy were recruited in seven separate centers to
      provide contemporaneous assessment of safety. The adverse-event profile and
      disability parameters were prospectively assessed. Patients were also screened at
      baseline and at 1, 3 and 6 months using the SF-36 health survey questionnaire.
      RESULTS: There were no life-threatening adverse events in either group. Overall,
      the number of significant clinical complications and adverse events was lower in
      women in the MRgFUS group compared to women undergoing hysterectomy. MRgFUS was
      associated with significantly faster recovery, including resumption of usual
      activities. At 6 months of follow-up, there were four (4%) treatment failures in
      the MRgFUS arm. Regarding SF-36 subscale scores, at 6 months there was
      improvement in all SF-36 subscales for both treatment groups. However, most of
      the SF-36 subscale scores were significantly better at this stage in the
      hysterectomy group than in the MRgFUS group. Women undergoing MRgFUS had steady
      improvement in all parameters throughout the 6-month follow-up period, despite
      the fact that they continued to have myomatous uteri and menstruation, which at
      baseline had given them significant symptomatology. CONCLUSIONS: The results of
      this study show that MRgFUS treatment of uterine leiomyomas leads to clinical
      improvement with fewer significant clinical complications and adverse events
      compared to hysterectomy at 6 months' follow-up.

PMID- 19852048
TI  - Measurement of compensatory hyperplasia of the contralateral kidney: usefulness
      for differential diagnosis of fetal unilateral empty renal fossa.
AB  - OBJECTIVE: To assess the usefulness of sonographic evaluation of compensatory
      hyperplasia of the contralateral kidney for the differential diagnosis of fetal
      unilateral empty renal fossa (ERF). METHODS: We retrospectively measured the
      ratio of the anteroposterior (AP) and transverse (TR) diameters of the
      contralateral kidney in 24 fetuses with unilateral ERF including 12 cases of
      unilateral renal agenesis, six cases of a unilateral pelvic kidney and six cases
      of a unilateral ectopic multicystic dysplastic kidney (MCDK). For the normal
      reference value, we calculated the AP : TR diameter ratios of both kidneys in 20
      normal fetuses in the second and third trimesters. We calculated the accuracy of
      the AP : TR ratio to detect contralateral compensatory hyperplasia. RESULTS: The
      median (range) AP : TR diameter ratios of the normal kidneys were 0.84 (0.72
      0.89) in the second trimester and 0.81 (0.65-0.89) in the third trimester. All
      cases of unilateral renal agenesis and ectopic MCDK showed the presence of
      compensatory hyperplasia, while no case of renal ectopy was seen with
      compensatory hyperplasia. The median (range) ratios for unilateral renal agenesis
      and ectopic MCDK were 1.0 (0.95-1.02) and 1.1 (1-1.25) in the second and third
      trimesters, respectively. The median ratios for a unilateral pelvic kidney were
      0.8 (0.74-0.85) and 0.77 (0.74-0.84) in the second and third trimesters,
      respectively. Using 0.9 as the discriminating value, the sensitivity,
      specificity, and accuracy of the AP : TR diameter ratio for the prenatal
      diagnosis of compensatory renal hyperplasia was 100%. CONCLUSION: Sonographic
      evaluation of compensatory hyperplasia of the contralateral kidney may be useful
      for the differential diagnosis of a fetal unilateral ERF. Prospective studies are
      warranted.

PMID- 19852049
TI  - Anatomy in the Third Reich: an outline, part 3. The science and ethics of anatomy
      in National Socialist Germany and postwar consequences.
AB  - Anatomists in National Socialist (NS) Germany did research on materials from
      animals and humans, including tissues from the bodies of NS victims. The research
      was competent but rarely innovative. This may be due to the isolation of the
      German research community from international developments, as well as to the
      dismissal of a great number of successful anatomists for racial or political
      reasons. Other research was unproductive because of its foundation in the
      pseudoscience of racial hygiene. Anatomists in the Third Reich acted according to
      a new set of medical ethics favored by the NS regime. Not the individual human
      being but the "body of the people" as a whole was the object of this ethics.
      Every action was ethical that ensured the health of the German people, including
      sterilization, so-called euthanasia, and finally mass murder. Anatomists made use
      of the opportunities given to them by the NS regime, which led to the postmortem
      utilization of the bodies of NS victims. After the war, most anatomists retained
      their positions and NS history was not discussed until the later 20th century.
      Since then, historical research and public discussions have led to an increased
      awareness of questions of ethics in anatomy. The history of anatomy in the Third
      Reich illustrates that the theory and practice of a science is dependent on the
      political system it exists in, and that the scientists' competence not only in
      their science but also in politics and ethics is a prerequisite for the freedom
      of science.

PMID- 19852050
TI  - Hic locus est Ubi Mortui Viveuntes Docent.

PMID- 19852051
TI  - The plastinate: lessons from the mummy and Kentai.

PMID- 19852052
TI  - Response to the letter to the editor by William E. Seidelman: Hermann Stieve's
      clinical-anatomical research on executed women during the "Third Reich".

PMID- 19852053
TI  - Anatomy in the Third Reich: an outline, part 1. National Socialist politics,
      anatomical institutions, and anatomists.
AB  - Although it is known that anatomists working in Germany during the Third Reich
      have used bodies of victims of the National Socialist (NS) regime for dissection
      and research, a comprehensive history of the anatomy in the Third Reich has not
      yet been written. Recent studies of the history of German anatomy departments
      during this time period provide material for a first outline of the subject
      matter. A historical review can help with the formulation of ethical foundations
      in modern anatomy. From the outset, the NS regime sought to reorganize German
      universities according to NS leadership principles and political goals. Many
      German academics, especially physicians and among them anatomists, followed these
      intentions with a voluntary "self-alignment" that encompassed their professional
      actions as well as their ethics. Currently, political information is available
      for 111 of 178 anatomists. Thirty-eight of the anatomists were dismissed for
      racial or political reasons, among them 10 chairmen of anatomy, whereas 35 of the
      anatomists were politically active members of one of the NS organizations. Over
      70% of the chairmen of anatomical departments in the time period from 1941 to
      1944 were members of NS organizations. Anatomists, as so many other physicians
      and academics, belonged both, to the group of victims of the regime, i.e., those
      being dismissed from their positions for racial and political reasons, and to the
      group of supporters and sometimes active perpetrators of NS policies.

PMID- 19852054
TI  - Anatomy in the Third Reich: an outline, part 2. Bodies for anatomy and related
      medical disciplines.
AB  - All anatomical departments of German universities used bodies of the executed and
      other victims of the National Socialist (NS) regime for their work. Many of these
      victims had been executed in prisons and were members of the German political
      opposition; others had perished in camps for prisoners of war or forced laborers
      and concentration camps, and were of various European and other descent.
      Anatomists generally welcomed the increased influx of "fresh material" for
      purposes of research and education of the growing numbers of medical students. No
      anatomist is known to have refused work with the bodies of NS victims. Other
      medical disciplines also made use of these bodies, among them were racial
      hygienists and neuropathologists. In the late 19th and early 20th century, the
      fields of anatomy, physical anthropology, and racial hygiene (eugenics) were
      closely related in their subject matter. Anatomists were involved in the
      biological foundation of racial hygiene, most prominently among them Eugen
      Fischer. The discipline was established as part of the medical curriculum after
      1920. Racial hygiene became the scientific justification for NS policies that led
      to racial discrimination, involuntary sterilization and ultimately mass murder.
      Anatomists taught racial hygiene throughout the Third Reich and did research in
      this area. Some were actively involved in NS policies through propaganda and
      evaluations for the so-called Genetic Health Courts, whereas others became
      victims of their own science in that they were dismissed for racial reasons.

PMID- 19852056
TI  - Stromal vascular progenitors in adult human adipose tissue.
AB  - The in vivo progenitor of culture-expanded mesenchymal-like adipose-derived stem
      cells (ADSC) remains elusive, owing in part to the complex organization of
      stromal cells surrounding the small vessels, and the rapidity with which adipose
      stromal vascular cells adopt a mesenchymal phenotype in vitro.
      Immunohistostaining of intact adipose tissue was used to identify three markers
      (CD31, CD34, and CD146), which together unambiguously discriminate histologically
      distinct inner and outer rings of vessel-associated stromal cells, as well as
      capillary and small vessel endothelial cells. These markers were used in
      multiparameter flow cytometry in conjunction with stem/progenitor markers (CD90
      and CD117) to further characterize stromal vascular fraction (SVF)
      subpopulations. Two mesenchymal and two endothelial populations were isolated by
      high speed flow cytometric sorting, expanded in short term culture, and tested
      for adipogenesis. The inner layer of stromal cells in contact with small vessel
      endothelium (pericytes) was CD146+/alpha-SMA+/CD90+/-/CD34-/CD31-; the outer
      adventitial stromal ring (designated supra adventitial-adipose stromal cells, SA
      ASC) was CD146-/alpha-SMA-/CD90+/CD34+/CD31-. Capillary endothelial cells were
      CD31+/CD34+/CD90+ (endothelial progenitor), whereas small vessel endothelium was
      CD31+/CD34-/CD90- (endothelial mature). Flow cytometry confirmed these expression
      patterns and revealed a CD146+/CD90+/CD34+/CD31- pericyte subset that may be
      transitional between pericytes and SA-ASC. Pericytes had the most potent
      adipogenic potential, followed by the more numerous SA-ASC. Endothelial
      populations had significantly reduced adipogenic potential compared with unsorted
      expanded SVF cells. In adipose tissue, perivascular stromal cells are organized
      in two discrete layers, the innermost consisting of CD146+/CD34- pericytes, and
      the outermost of CD146-/CD34+ SA-ASC, both of which have adipogenic potential in
      culture. A CD146+/CD34+ subset detected by flow cytometry at low frequency
      suggests a population transitional between pericytes and SA-ASC.

PMID- 19852058
TI  - What's new in the laryngoscope.

PMID- 19852057
TI  - Response to "Hermann Stieve's clinical-anatomical research on executed women
      during the 'Third Reich'" by Winkelmann and Schagen.

PMID- 19852059
TI  - What is the role of long-term macrolide therapy in the treatment of recalcitrant
      chronic rhinosinusitis?

PMID- 19852060
TI  - Development of small and inexpensive digital data acquisition systems using a
      microcontroller-based approach.
AB  - Fully digital data acquisition systems for use in flow cytometry provide
      excellent flexibility and precision. Here, we demonstrate the development of a
      low cost, small, and low power digital flow cytometry data acquisition system
      using a single microcontroller chip with an integrated analog to digital
      converter (ADC). Our demonstration system uses a commercially available
      evaluation board making the system simple to integrate into a flow cytometer. We
      have evaluated this system using calibration microspheres analyzed on commercial,
      slow-flow, and CCD-based flow cytometers. In our evaluations, our demonstration
      data system clearly resolves all eight peaks of a Rainbow microsphere set on both
      a slow-flow flow cytometer and a retrofitted BD FACScalibur, which indicates it
      has the sensitivity and resolution required for most flow cytometry applications.
      It is also capable of millisecond time resolution, full waveform collection, and
      selective triggering of data collection from a CCD camera. The capability of our
      demonstration system suggests that the use of microcontrollers for flow cytometry
      digital data-acquisition will be increasingly valuable for extending the life of
      older cytometers and provides a compelling data-system design approach for low
      cost, portable flow cytometers.

PMID- 19852061
TI  - Adjuvant dendritic cell-based tumour vaccination for children with malignant
      brain tumours.
AB  - BACKGROUND: A large experience with dendritic cell (DC)-based vaccination for
      malignant brain tumours has been gained in adults. Here we focus on the results
      obtained in children with relapsed malignant brain tumours. PROCEDURE: In total
      45 children were vaccinated: 33 high grade glioma (HGG), 5 medulloblastoma
      (MB)/primitive neuro-ectodermal tumour (PNET), 4 ependymoma and 3 atypical
      teratoid-rhabdoid tumour (ATRT). Autologous, monocyte-derived DC were generated
      and loaded with tumour lysate, which was used as source of tumour-associated
      antigens. RESULTS: In 38 patients peripheral blood mononuclear cells (PBMC) were
      obtained from leukapheresis and in 7 patients from fresh blood samples. 7 HGG
      patients are still alive with median follow-up (FU) of 35.7 months (range: 12.1
      85.6). Median overall survival (OS) was 13.5 months (range: 1.4-85.6). All
      patients with MB/PNET died (median OS 5.7 months; range 4.3-51.2). One patient
      with ependymoma is still alive at 22.3 months FU. The other three patients died
      at, respectively, 7.7, 30.1 and 31.5 months. Two patients with ATRT are still
      alive at, respectively, 34.1 and 52.6 months FU. The third patient died at 50.5
      months. No severe adverse events were noticed. CONCLUSIONS: In this exploratory
      study, HGG and ATRT seem to respond more favourably to vaccination than MB/PNET
      and ependymoma. Although preliminary, our results are promising and support
      further testing of DC-based immunotherapy in new treatment protocols for HGG and
      ATRT.

PMID- 19852062
TI  - Coding microsatellite instability analysis in microsatellite unstable small
      intestinal adenocarcinomas identifies MARCKS as a common target of inactivation.
AB  - Approximately 15% of small intestinal adenocarcinomas show inactivation of DNA
      mismatch repair (MMR) and display high-level microsatellite instability (MSI-H).
      MSI-H tumors progress as a result of mutations affecting coding microsatellites
      (coding microsatellite instability, cMSI) that may result in a functional
      inactivation of the encoded proteins and provide a selective growth advantage for
      the affected cell. To investigate the cMSI selection in small intestinal
      carcinogenesis 56 adenocarcinomas were tested for MSI. Eleven MSI-H carcinomas
      (19.6%) were identified and subjected to cMSI analysis in 24 potentially tumor
      relevant genes. Mutation frequencies were similar to those observed in colorectal
      cancer (CRC). Beside high frequencies of cMSI in TGFbetaR2, ACVR2, and AIM2 we
      detected MARCKS mutations in 10 out of 11 (91%) tumors with a 30% share of
      biallelic mutations. Since little is known about MARCKS expression in the
      intestine, we analyzed MARCKS protein expression in 31 carcinomas. In non
      neoplastic mucosa, MARCKS was found to be expressed with a concentration gradient
      along the crypt-villus axis. In line with cMSI induced functional inactivation of
      MARCKS, 8 out of 11 MSI-H adenocarcinomas showed regional or complete loss of the
      protein. In microsatellite stable (MSS) small bowel adenocarcinoma, loss of
      MARCKS expression was seen in 2 out of 20 tumors (10%). In conclusion, we herein
      present a cMSI profile of MSI-H small intestinal adenocarcinomas identifying
      MARCKS as a frequent target of mutation. Loss of MARCKS protein expression
      suggests a significant role of MARCKS inactivation in the pathogenesis of small
      intestinal adenocarcinomas.

PMID- 19852063
TI  - Hyaluronic acid ameliorates bladder hyperactivity via the inhibition of H2O2
      enhanced purinergic and muscarinic signaling in the rat.
AB  - AIMS: We hypothesize that increased H(2)O(2) in the urinary bladder may affect
      ATP and acetylcholine release and activate urothelial purinergic and muscarinic
      signaling consequently leading to hyperactive bladder. MATERIALS AND METHODS: We
      infused 0.3% and 1.5% H(2)O(2) to the urinary bladder to evaluate the voiding
      function and frequency, pelvic afferent (PANA) and pelvic efferent nerve activity
      (PENA) simultaneously in the urethane anesthetized rats. We measured ATP and
      acetylcholine content in the rat urinary bladder under saline or H(2)O(2)
      stimulation. Hyaluronic acid, muscarinic, and purinergic receptor antagonists
      were used to evaluate their effects and mechanisms on H(2)O(2)-induced
      hyperactive bladder. RESULTS: Intravesical H(2)O(2) administration increased the
      frequency of voiding and the maximal amplitude of intravesical pressure (IVP) in
      the urethane anesthetized rats. Intravesical H(2)O(2) decreased the threshold
      level of PANA and PENA for triggering micturition and increased ATP and
      acetylcholine contents in the H(2)O(2)-treated bladder in the rat. Hyaluronic
      acid in vitro directly scavenged H(2)O(2) in a dose-dependent manner.
      Intravesical hyaluronic acid for 30 min attenuated H(2)O(2)-elicited excitatory
      effects on the frequency of voiding, amplitude of IVP and the sensitization of
      PANA and PENA in the rats. Hyaluronic acid treatment reduced H(2)O(2)-induced ATP
      and acetylcholine release in the urinary bladder. Intravesical administration of
      muscarinic receptor antagonist atropine methyl nitrate (50 microM) or purinergic
      receptor antagonist PPADS (1 mM) ameliorated H(2)O(2)-induced hyperactive
      bladder. CONCLUSIONS: These results indicate that hyaluronic acid treatment can
      ameliorate H(2)O(2)-induced bladder hyperactivity possibly via the antioxidant
      activity and the inhibition of activating purinergic and muscarinic signaling
      pathway.

PMID- 19852064
TI  - Voiding dysfunctions in children with mental retardation.
AB  - AIMS: This study aims to evaluate the voiding disorder and lower urinary tract
      symptoms in mentally retarded children. METHODS: Fifty-one mentally retarded
      children (age 7.7 years) was assessed. A volunteer sample comprised of 36
      typically developing children (age 6.4 years) served as the comparative group.
      All participants underwent uroflometric investigation, and residual urine was
      detected by sonography. Urological history including history of urinary tract
      infection, incontinence, frequency, and dysurea was collected. In addition, the
      mentally retarded group was classified according to IQ: severe mentally retarded
      group (IQ below 40) (n = 11), moderate mentally retarded group (IQ: 41 to 55) (n
      = 19), mild mentally retarded group (IQ: 56 to 70) (n = 21). Group comparisons
      were analyzed using Chi-square and Student's t-test. RESULTS: Of the 51 mentally
      retarded children, 18(35.2%) were found to have voiding dysfunction, which is
      significantly higher than the control group (8.3%). The incidence of urine
      incontinence and frequency is also significantly higher in the mentally retarded
      group. The comparison of the three mentally retarded subgroups showed that the
      severe mentally retarded group had the highest incidence of voiding dysfunction
      and urinary incontinence. Overall, the mentally retarded group had higher
      percentage of small bladder capacity. CONCLUSIONS: We concluded that mentally
      retarded children have a higher incidence of voiding dysfunction and incontinence
      than the control group. Early detection of voiding dysfunction in an objective,
      non-invasive manner is important in mentally retarded children, particularly
      those with severe cognitive impairment.

PMID- 19852066
TI  - Hemoglobin Hakkari: an autosomal dominant form of beta thalassemia with inclusion
      bodies arising from de novo mutation in exon 2 of beta globin gene.
AB  - Certain beta globin gene mutations produce a thalassemia major phenotype in the
      heterozygous state. While most such patients have thalassemia intermedia, we
      describe a young Guatemalan child with a de novo mutation in the beta globin
      gene, codon 31 T --> G (Hemoglobin Hakkari), who developed severe anemia at the
      age of 10 months and remains transfusion-dependent. The substitution of B13
      leucine with arginine in the beta globin results in alteration of a critical heme
      contact point resulting in an extremely unstable variant hemoglobin and a
      clinical picture that is characterized by ineffective erythropoiesis and numerous
      intracytoplasmic inclusions within the erythrocyte precursors of the bone marrow.
      .

PMID- 19852065
TI  - Organization of the posterior parietal cortex in galagos: I. Functional zones
      identified by microstimulation.
AB  - We used half-second trains of intracortical microstimulation to study the
      functional organization of the posterior parietal cortex (PPC) in prosimian
      galagos. These trains of current pulses evoked meaningful behaviors from the
      anterior, but not posterior, half of PPC. Stimulation of dorsal PPC caused
      contralateral forelimb movements, including defensive, hand-to-mouth, and
      reaching movements. Defensive and hand-to-mouth movement territories overlapped,
      although hand-to-mouth movements were usually evoked from more rostrolateral
      sites than defensive movements. Reaching movement sites were typically more
      caudal than defensive or hand-to-mouth movement sites. Stimulation of the most
      medial PPC sites evoked complex movements of forelimbs and hindlimbs. Ventral PPC
      commonly represented defensive face movements. Similar defensive movements, with
      the addition of widely opening the mouth to expose the teeth, were elicited from
      a small area in front of the PPC defensive face zone. Sometimes defensive face
      movements occurred with forelimb movements. Thus, subregions of PPC relate to
      different ethologically relevant categories of behavior. Most movements were
      initiated within 33-100 msec after stimulus onset. Face, eye blink, and ear
      movements were generally less delayed than forelimb movements. The present
      results in galagos, together with those obtained from macaque monkeys by Graziano
      and coworkers (Graziano et al. [2002a] Neuron 34:841-851; Cooke et al., [2003]
      Proc. Natl. Acad. Sci. U.S.A. 100:6163-6168), suggest that the functional
      involvement of the PPC in specific types of sensorimotor behavior evolved early
      in the course of primate evolution and that networks for complex movements
      involving motor and posterior parietal areas are characteristic of all primate
      brains.

PMID- 19852067
TI  - Cumulus cell-enclosed oocytes acquire a capacity to synthesize GSH by FSH
      stimulation during in vitro maturation in pigs.
AB  - We investigated (i) follicle stimulating hormone (FSH)-modulated changes in the
      expression of glutathione (GSH) and its rate-limiting enzyme, glutamate cysteine
      ligase (GCL), in porcine oocytes and cumulus cells, and (ii) the contribution of
      gap-junctional communications (GJCs) in cumulus-oocyte complexes (COCs) to
      intraoocyte GSH accumulation. In experiment (i), COCs were cultured for 48 h with
      (+FSH group) or without FSH (-FSH group). The GSH content of oocytes increased
      with cultivation time in the +FSH group, but decreased in the -FSH group. The GSH
      content of cumulus cells at 48 h was also higher in the +FSH group than that in
      the -FSH group. Expression of GCL subunit mRNAs in oocytes and cumulus cells was
      increased by FSH stimulation until 12 h, and then fell to the baseline level. On
      the other hand, the amount of GCL subunit proteins in oocytes and cumulus cells
      increased gradually throughout the period of culture with FSH. In experiment
      (ii), blocking of GJCs in COCs during 0-24 h of culture led to a decrease in the
      GSH content of oocytes at 24 h of culture, whereas the GSH content at 48 h of
      culture did not differ even after blocking of the GJCs during 24-48 h of culture.
      These findings indicate that FSH initiates GSH synthesis in cumulus cells and
      oocytes by modulating the expression of GCL, and that porcine oocytes are able to
      synthesize GSH without GJC-mediated support from cumulus cells, at least in the
      later half of maturation culture.

PMID- 19852068
TI  - Effects of 660-nm gallium-aluminum-arsenide low-energy laser on nerve
      regeneration after acellular nerve allograft in rats.
AB  - PURPOSE: The purpose of this study was to explore and discuss the effects of 660
      nm gallium-aluminum-arsenide low-energy laser (GaAlAs LEL) irradiation on neural
      regeneration after acellular nerve allograft repair of the sciatic nerve gap in
      rats. METHODS: Eight male and female Sprague-Dawley rats were used as nerve
      donors, and 32 healthy Wistar rats were randomly divided into four groups: normal
      control group, acellular rat sciatic nerve (ARSN) group, laser group, and
      autograft group. Twelve weeks after surgery, nerve conduction velocity,
      restoration rate of tibialis anterior wet muscle weight, myelinated nerve number,
      and calcitonin gene-related peptide (CGRP) protein and mRNA expression of the
      spinal cord and muscle at the injury site were quantified and statistically
      analyzed. RESULTS: Compared with the ARSN group, laser therapy significantly
      increased nerve conduction velocity, restoration rate of tibialis anterior wet
      muscle weight, myelinated nerve number, and CGRP protein and mRNA expression of
      the L(4) spinal cord at the injury site. CONCLUSIONS: These findings demonstrate
      that 660-nm GaAlAs LEL therapy upregulates CGRP protein and mRNA expression of
      the L(4) spinal cord at the injury site and increases the rate of regeneration
      and target reinnervation after acellular nerve allograft repair of the sciatic
      nerve gap in rats. Low-energy laser irradiation may be a useful, noninvasive
      adjunct for promoting nerve regeneration in surgically induced defects repaired
      with ARSN.

PMID- 19852069
TI  - Effects of cAMP-dependent protein kinase activator and inhibitor on in vivo
      rolipram binding to phosphodiesterase 4 in conscious rats.
AB  - Rolipram is a selective inhibitor of phosphodiesterase-4 (PDE4), and positron
      emission tomography (PET) using [(11)C]rolipram can monitor the in vivo activity
      of this enzyme that is part of the cAMP second messenger cascade. cAMP-dependent
      protein kinase (PKA) phosphorylates PDE4 and increases both enzyme activity and
      affinity for rolipram. In the present PET study, we examined effects of PKA
      modulators in conscious rats on the binding of [(11)C](R)-rolipram in comparison
      to the much less active enantiomer [(11)C](S)-rolipram. Unilateral injection of a
      PKA activator (dibutyryl-cAMP) and a PKA inhibitor (Rp-adenosine-3',5'-cyclic
      monophosphorothioate) into the striatum significantly increased and decreased,
      respectively, the binding of [(11)C](R)-rolipram. These effects were not caused
      by changes in blood flow or delivery of radioligand to brain, since these agents
      had no effect on the binding of [(11)C](S)-rolipram binding. These results
      support the value of measuring in vivo [(11)C](R)-rolipram binding in brain to
      assess responses to physiological or pharmacological challenges to the cAMP
      second messenger system.

PMID- 19852070
TI  - N-ethyl lidocaine (QX-314) protects striatal neurons against ischemia: an in
      vitro electrophysiological study.
AB  - In this study, we have investigated the neuroprotective actions of the membrane
      impermeable, lidocaine analog, N-ethyl lidocaine (QX-314) in the striatum. The
      effects of this drug were compared with those caused by the strictly-related
      compound and sodium channel blocker lidocaine. To address this issue,
      electrophysiological recordings were performed in striatal slices, in control
      condition (normoxia) and during combined oxygen and glucose deprivation (in vitro
      ischemia). Either QX-314 or lidocaine induced, to some extent, a protection of
      the permanent electrophysiological alteration (field potential loss) caused by a
      period (12 min) of ischemia. Thus, both compounds permitted a partial recovery of
      the ischemic depression of the corticostriatal transmission and reduced the
      amplitude of the ischemic depolarization in medium spiny neurons. However, while
      QX-314, at the effective concentration of 100 microM, slightly reduced the
      amplitude of the excitatory field potential and did not affect the current-evoked
      spikes discharge of medium spiny striatal neurons, equimolar lidocaine depressed
      the field potential and eliminated repetitive spikes on a depolarizing step. On
      the basis of these observations, our results suggest the use of QX-314 as a
      neuroprotective agent in ischemic brain disorders.

PMID- 19852071
TI  - Dopamine transporter PET in normal aging: dopamine transporter decline and its
      possible role in preservation of motor function.
AB  - OBJECTIVES: To determine the impact of age-related decline in dopamine
      transporter (DAT) expression on motor function in the elderly. METHODS: About 33
      normal individuals of a wide age range were scanned with PET employing d-threo
      [(11)C]-methylphenidate (MP, a marker of DAT) and [(11)C]-dihydrotetrabenazine
      (DTBZ, that binds to the vesicular monoamine transporter Type 2). Motor function
      was assessed using the Purdue Pegboard Test (PPB). We analyzed the relationship
      between [(11)C]-MP and motor performance. RESULTS: Age ranged from 27- to 77-year
      old (mean +/- SD, 54.75 +/- 14.14). There was no age-related decline in binding
      potentials (BP) for [(11)C]-DTBZ. In contrast, [(11)C]-MP BP was inversely
      related to age in all striatal regions analyzed (caudate: reduction of 11.2% per
      decade, P < 0.0001, r = -0.86; putamen: reduction of 10.5% per decade, P <
      0.0001, r = -0.80). A differential effect of [(11)C]-MP on PPB could be observed
      according to age group. There was a positive relation between the PPB and [(11)C]
      MP in young individuals (coefficient = 13.56), whereas in individuals greater
      than 57 years this relationship was negative (coefficient = -19.53, P = 0.031).
      CONCLUSIONS: Our findings confirm prior observations of age-related DAT decline
      and suggest that this phenomenon is independent of changes in VMAT2. After the
      fifth decade of life, this reduction in DAT binding is associated with a motor
      performance comparable to mid-adult life. These findings imply that biochemical
      processes associated with healthy aging may offset the naturaldecline in motor
      function observed in the elderly.

PMID- 19852073
TI  - Synaptic recruitment of AMPA glutamate receptor subunits in levodopa-induced
      dyskinesia in the MPTP-lesioned nonhuman primate.

PMID- 19852074
TI  - Trace metal dynamics in zooplankton from the Bay of Bengal during summer monsoon.
AB  - Trace metal (Fe, Co, Ni, Cu, Zn, Cd, and Pb) concentrations in zooplankton from
      the mixed layer were investigated at 8 coastal and 20 offshore stations in the
      western Bay of Bengal during the summer monsoon of 2003. The ecotoxicological
      importance of trace metal uptake was apparent within the Bay of Bengal
      zooplankton. There was a distinct spatial heterogeneity of metals, with highest
      concentrations in the upwelling zones of the southeast coast, moderate
      concentrations in the cyclonic eddy of the northeast coast, and lowest
      concentrations in the open ocean warm gyre regions. The average trace metal
      concentrations (MUg g-1) in coastal zooplankton (Fe, 44894.1 +/- 12198.2; Co,
      46.2 +/- 4.6; Ni, 62.8 +/- 6.5; Cu, 84.9 +/- 6.7; Zn, 7546.8 +/- 1051.7; Cd, 46.2
      +/- 5.6; Pb, 19.2 +/- 2.6) were higher than in offshore zooplankton (Fe, 3423.4
      +/- 681.6; Co, 19.5 +/- 3.81; Ni, 25.3 +/- 7.3; Cu, 29.4 +/- 4.2; Zn, 502.3 +/-
      124.3; Cd, 14.3 +/- 2.9; Pb, 3.2 +/- 2.0). A comparison of average trace metal
      concentrations in zooplankton from the Bay of Bengal showed enrichment of Fe, Co,
      Ni, Cu, Zn, Cd, and Pb in coastal zooplankton may be related to metal absorption
      from primary producers, and differences in metal concentrations in phytoplankton
      from coastal waters (upwelling zone and cyclonic eddy) compared with offshore
      waters (warm gyre). Zooplankton showed a great capacity for accumulations of
      trace metals, with average concentration factors of 4 867 929 +/- 569 971, 246
      757 +/- 51 321, 337 180 +/- 125 725, 43 480 +/- 11 212, 1 046 371 +/- 110 286,
      601 679 +/- 213 949, and 15 420 +/- 9201 for Fe, Co, Ni, Cu, Zn, Cd, and Pb with
      respect to dissolved concentrations in coastal and offshore waters of the Bay of
      Bengal. (c) 2009 Wiley Periodicals, Inc. Environ Toxicol, 2009.

PMID- 19852072
TI  - Altered response to antidepressant treatment in FoxG1 heterozygous knockout mice.
AB  - Evidence from a variety of sources suggests that structural alterations in the
      brain, including neurogenesis, may play a role in both the pathogenesis of mood
      disorders and the mechanism of action of antidepressants. Previous studies have
      implicated both the transforming growth factor-beta (TGF-beta), and the
      phosphatidyl inositol-3 kinase (PI3K)-Akt pathways in the neurogenesis-promoting
      and behavioral properties of antidepressants. Forkhead box protein G1 (FoxG1) is
      a major regulator of both of these pathways, and FoxG1 heterozygous null mice
      (FoxG1+/-) have previously been reported to have deficits in adult hippocampal
      neurogenesis and behavioral abnormalities including deficits in contextual fear
      learning. However the role of FoxG1, if any, in the response to antidepressants
      has not been previously investigated.To investigate the role of the FoxG1 gene in
      the behavioral and neurogenic properties of antidepressants, we tested FoxG1+/-
      mice and littermate controls in two different rodent models of antidepressant
      action: the tail suspension test and the forced swim test. FoxG1+/- mice showed
      no response to antidepressants in either of these tests. These results suggest
      that normal levels of FoxG1 may be required for the behavioral response to
      antidepressants.

PMID- 19852075
TI  - Response and recovery of hybrid sturgeon from subchronic oral administration of
      cyanobacteria.
AB  - A 90-day growth trial was conducted on hybrid sturgeon (Acipenser baeri ? * A.
      gueldenstaedtii ?) to investigate the effect of dietary inclusion of
      cyanobacteria on growth, feed utilization, and fish tissue microcystins (MCs)
      accumulation and the recovery of fish when they were free of cyanobacteria. Four
      diets were formualted isonitrogenous and isocaloric to contain different MCs
      concentrations: the control diet (free of cyanobacteria), low cyanobacteria diet
      (LCD, 26.60 MUg MCs/g diet), medium cyanobacteria diet (MCD, 78.82 MUg MCs/g
      diet), and high cyanobacteria diet (HCD, 201.03 MUg MCs/g diet). During the first
      47 days, each diet was fed to fish in five replicates and then all fish were fed
      the control diet during the next 43 days. The results showed that a dose
      dependent decrease in feeding rate (FR) and specific growth rate (SGR) were
      observed in the fish fed with MCD and HCD. MCs contents in fish liver, intestine,
      and dorsal white muscle increased with dietary MCs and were time dependent (P <
      0.05). After the 43-day recovery, there were no significant differences in FR or
      SGR between the fish previously fed LCD or MCD and the fish fed with the control
      diet (P > 0.05), while the fish previously fed HCD showed higher FR and SGR than
      those fed the control diet (P < 0.05). MCs clearance in fish liver and intestine
      showed time-dependence during the 43-day recovery.

PMID- 19852077
TI  - Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and
      recent update from clinical pharmacology perspectives.
AB  - The introduction of irinotecan has revolutionized the applicability of
      camptothecins as predominant topoisomerase I inhibitor for anti-cancer therapy.
      The potent anti-tumor activity of irinotecan is due to rapid formation of an in
      vivo active metabolite, SN-38. Therefore, irinotecan is considered as a pro-drug
      to generate SN-38. Over the past decade, side-by-side with the clinical
      advancement of the use of irinotecan in the oncology field, a plethora of
      bioanalytical methods have been published to quantify irinotecan, SN-38 and other
      metabolites. Because of the availability of HPLC, LC-MS and LC-MS/MS methods, the
      pharmacokinetic profiling of irinotecan and its metabolites has been accomplished
      in multiple species, including cancer patients. The developed assays continue to
      find use in the optimization of newly designed delivery systems with regard to
      pharmacokinetics to promote safe and effective use of either irinotecan or SN-38.
      This review intends to: firstly, provide an exhaustive compilation of the
      published assays for irinotecan, SN-38 and other metabolite(s) of irinotecan, as
      applicable; secondly, to enumerate the validation parameters and applicable
      conclusions; and thirdly, provide some recent perspectives in the clinical
      pharmacology arena pertaining to efflux transporters, pediatric profiling, role
      of kidney function in defining toxicity, drug-drug interaction potential of
      irinotecan, etc.

PMID- 19852076
TI  - Effects of the Fas/Fas-L pathway on fluoride-induced apoptosis in SH-SY5Y cells.
AB  - The mechanisms underlying fluoride-induced apoptosis in neurons still remain
      unknown. To investigate apoptosis, caspase-3 activity, and mRNA expression of
      Fas, Fas-L, and caspases (-3 and -8) induced by fluoride, human neuroblastoma (SH
      SY5Y) cells were incubated with 0, 20, 40, and 80 mg/L sodium fluoride (NaF) for
      24 h in vitro. The data show that cell viability in the 40 and 80 mg/L fluoride
      groups were significantly lower than that of the control group. The percentages
      of apoptosis in the 40 and 80 mg/L fluoride groups were markedly higher than
      those in the control group, and they increased with the increase in fluoride
      concentration. The activity of caspase-3 and mRNA expression levels for Fas, Fas
      L, and caspases (-3 and -8) in the 40 and 80 mg/L fluoride groups were
      significantly higher than those in the control group. An agonistic anti-Fas
      monoclonal antibody (CH-11) significantly augmented apoptosis induction by
      fluoride, showing a synergistic effect, while a Fas-blocking antibody (ZB4)
      partly inhibited fluoride-induced apoptosis of SH-SY5Y cells. The results
      indicate that fluoride exposure could induce apoptosis in SH-SY5Y cells, and the
      Fas/Fas-L signaling pathway may play an important role in the process.

PMID- 19852078
TI  - Inflammatory bowel disease.

PMID- 19852079
TI  - Comment on "Quality of drug interaction alerts in prescribing and dispensing
      software".

PMID- 19852080
TI  - Proceedings of the Procida Update on Psoriatic Disease, May 22-24, 2008, Procida,
      Italy.

PMID- 19852081
TI  - [Life-long professional education].

PMID- 19852082
TI  - [Preparing a plan for continuing education].

PMID- 19852083
TI  - Vitamins and minerals. What you should know about essential nutrients.

PMID- 19852084
TI  - [Genopole: a genesis of ten long years].
AB  - At the beginning of 1990s, the first human genome maps put in the front of the
      scene the very large scale biology. However, it will take a decade to convince
      the French scientists of the interest of this approach and the politicians of
      that to invest in the future Genopole, a "genomic valley" who will group together
      researchers, academics and industrialists.

PMID- 19852085
TI  - [Designing Genopole, a new concept and actor for science, technology and
      innovation policy in France].
AB  - At the dawn of the 20th century, the economic dynamics of modern biotechnology in
      the USA was coming from scientific and industrial centres. These bio parks
      combined the development of academic knowledge with innovating industrial and
      biomedical activities using public and private fundings. In France, the goal of
      competitiveness within a knowledge-based economy focusing on life sciences, led
      the government to change its institutional schemes supporting innovation. The
      creation of Genopole in Evry in 1998 institutionalizes a bifurcation in Science
      and Technology public policy to diffusion-oriented instruments. This centre of
      excellence connected together heterogeneous partners and resources around large
      scale facilities and the implementation of a technological and logistic support
      to stimulate start up companies. Although the dynamics created by Genopole for
      both the knowledge base and commercialisation in genomics is a unique outcome of
      a public/private combination and national/local process, this experimental
      intermediary institution generated new bridges between science and society.

PMID- 19852086
TI  - [Biotechnology, the key to therapeutic innovation in the field of health].
AB  - The therapeutic innovation cannot be conceived today without biotechnology. Their
      insights on current development, the short-term outlook, and how to boost the
      sector health. Facilitate their development, it is also, during the last ten
      years, the work of Biopark Genopole and young biotechnology companies from the
      public and private researches.

PMID- 19852087
TI  - [Synthetic and integrative biology].
AB  - Integrative biology currently undergoes a deep renewal as we witness the
      increasing influence of systems biology, which explores life's logic, and of
      synthetic biology, which exploits it.

PMID- 19852089
TI  - [Basic examination before clinical examination. That is why it is worthwhile to
      return to the laboratory].

PMID- 19852088
TI  - A non-heme iron-mediated chemical demethylation in DNA and RNA.
AB  - DNA methylation is arguably one of the most important chemical signals in
      biology. However, aberrant DNA methylation can lead to cytotoxic or mutagenic
      consequences. A DNA repair protein in Escherichia coli, AlkB, corrects some of
      the unwanted methylations of DNA bases by a unique oxidative demethylation in
      which the methyl carbon is liberated as formaldehyde. The enzyme also repairs
      exocyclic DNA lesions--that is, derivatives in which the base is augmented with
      an additional heterocyclic subunit--by a similar mechanism. Two proteins in
      humans that are homologous to AlkB, ABH2 and ABH3, repair the same spectrum of
      lesions; another human homologue of AlkB, FTO, is linked to obesity. In this
      Account, we describe our studies of AlkB, ABH2, and ABH3, including our
      development of a general strategy to trap homogeneous protein-DNA complexes
      through active-site disulfide cross-linking. AlkB uses a non-heme mononuclear
      iron(II) and the cofactors 2-ketoglutarate (2KG) and dioxygen to effect oxidative
      demethylation of the DNA base lesions 1-methyladenine (1-meA), 3-methylcytosine
      (3-meC), 1-methylguanine (1-meG), and 3-methylthymine (3-meT). ABH3, like AlkB,
      works better on single-stranded DNA (ssDNA) and is capable of repairing damaged
      bases in RNA. Conversely, ABH2 primarily repairs lesions in double-stranded DNA
      (dsDNA); it is the main housekeeping enzyme that protects the mammalian genome
      from 1-meA base damage. The AlkB-family proteins have moderate affinities for
      their substrates and bind DNA in a non-sequence-specific manner. Knowing that
      these proteins flip the damaged base out from the duplex DNA and insert it into
      the active site for further processing, we first engineered a disulfide cross
      link in the active site to stabilize the Michaelis complex. Based on the detailed
      structural information afforded by the active-site cross-linked structures, we
      can readily install a cross-link away from the active site to obtain the native
      like structures of these complexes. The crystal structures show a distinct base
      flipping feature in AlkB and establish ABH2 as a dsDNA repair protein. They also
      provide a molecular framework for understanding the demethylation reaction
      catalyzed by these proteins and help to explain their substrate preferences. The
      chemical cross-linking method demonstrated here can be applied to trap other
      labile protein-DNA interactions and can serve as a general strategy for exploring
      the structural and functional aspects of base-flipping proteins.

PMID- 19852090
TI  - [Atorvastatin dreduces sympathetic activity and improves baroreceptor reflex
      sensitivity in patients with hypercholesterolemia and hypertension].

PMID- 19852091
TI  - [Ambulatory cardiac rehabilitation - can its utilization be improved?].

PMID- 19852092
TI  - [Genetic evaluation of inflammation reaction and coronary disease].

PMID- 19852093
TI  - [Elevated levels of inflammation reactive factors as a sign of restenosis after
      stenting].

PMID- 19852095
TI  - [Can results of STICH examination be saved? Obviously, yes!].

PMID- 19852094
TI  - [Myocarditis - challenge for contemporary cardiology].

PMID- 19852096
TI  - To mesh or not to mesh, that is the question: comment on "Use of Seamguard to
      prevent pancreatic leak following distal pancreatectomy".

PMID- 19852097
TI  - "Hardening of the arteries" is a systemic disease: comment on "Ischemic colitis
      after endovascular aortoiliac aneurysm repair".

PMID- 19852098
TI  - HBV and HCC: comment on "Role of hepatitis B virus infection in the prognosis
      after hepatectomy for hepatocellular carcinoma in patients with cirrhosis: a
      Western dual-center experience".

PMID- 19852099
TI  - Possible lack of survival advantage for one group: comment on "Predictors of long
      term mortality after bariatric surgery performed in Veterans Affairs medical
      centers".

PMID- 19852100
TI  - Questions regarding surgery to correct short-segment BE: comment on "Late results
      of the surgical treatment of 125 patients with short-segment Barrett esophagus".

PMID- 19852101
TI  - Searching for the source of venous clots: an unsolved old problem: comment on
      "Pulmonary embolism and deep venous thrombosis in trauma: are they related?".

PMID- 19852103
TI  - [Importance of studies about the etiopathogenesis of childhood diseases for
      clinical practice. Introduction].

PMID- 19852102
TI  - [Medicine and the sexual distribution of work: an analysis of the scientific
      discourse on the role of the "human factor" in improving performance at work
      (Spain, 1922-1936)].
AB  - During the first third of the twentieth century, and especially after the 1920s,
      a discourse on occupational hygiene and safety began to develop in Spain. This
      discourse, without rejecting the value of the work carried out in the factory
      environment, particularly stressed the need to take into account what was called
      the "human factor." Promoted mainly by the budding occupational doctors and
      psychologists, this discourse became part of both the lines of biological
      thinking of constitutional pathology as well as the economic ideas of the so
      called OCT, and it expounded the need to take the somatic and psychic
      characteristics of people into account in order to carry out "rational"
      distribution of the same in the workplace. The article aims to highlight the way
      in which this discourse contained elements that would help to attribute specific
      roles within the workplace based on the biological and psychological
      characteristics of men and women, so facilitating the legitimisation of a sexual
      distribution of work which helped to reinforce the social organization of gender
      at that time.

PMID- 19852104
TI  - [Toward healthy offspring: early prenatal testing in Spain].
AB  - This paper deals with prenatal diagnosis practices in Spain. For pursuing this
      aim it reviews both literature on the origins of these practices in foreign
      countries as well as some of the early publications by Spanish practitioners.
      Those publications appeared to be connected to previous genetic testing in
      children such as the case of Down syndrome. Socio-political norms and values of
      Franco's regime together with clinicians' interests on introducing new testing
      techniques resulted in the stabilization of these practices associated to a
      reconceptualisation of pregnancy. Although prenatal diagnosis techniques made the
      body of pregnant women invisible, women's bodies remained at the core of the
      technicalisation of contemporary reproductive options.

PMID- 19852105
TI  - Hemoprotein formation in yeast. VI. Mutants with changed levels of catalase and
      of other heme enzymes under conditions of glucose repression.
AB  - Three mutants with altered response of the hemoprotein level to glucose
      repression and anoxia were characterized biochemically. Two mutants show complete
      resistance of catalase activity to glucose repression and a lower degree of
      resistance of cytochrome c oxidase and of some other enzymes. Liquid nitrogen
      spectra of these mutants grown in high glucose medium are typical for those of
      glusoce-derepressed spectra of wild-type cells. The third mutant is
      hypersensitive to glucose repression and shows only traces of catalase T activity
      when grown in high-glucose media. In these conditions its spectrum is almost
      devoid of typical peaks of cytochromes. When grown on ethanol or raffinose it
      forms catalase and shows a typical derepressed spectrum of cytochromes. The
      regulatory mechanism impaired in the mutants is not known. It seems likely that
      the regulation of the heme pathway in the mutants does not differ from that of
      the wild-type.

PMID- 19852106
TI  - Hemoprotein formation in yeast. VII. Genetic analysis of pleiotropic mutants
      affected in the response to glucose repression and anoxia.
AB  - Genetical analysis of three pleiotropic mutants with changed regulation of
      hemoprotein level was performed. It was proved that single recessive mutations
      cgr4, cas1 and cgh1 are responsible for simultaneous changes of catalase T,
      cytochrome c oxidase and of some other enzyme levels, in glucose repression
      conditions. Two mutations cgr4 and cas1, responsible for glucose resistance of
      hemoprotein formation in aerobic conditions enable also anaerobic synthesis of
      catalase T. Mutation cgh1 causing hypersensitivity of several respiratory enzymes
      to glucose repression is partly epistatic to cas1 and cgr4 mutations.

PMID- 19852107
TI  - Cloning of Aspergillus nidulans DNA. I. Selection and analysis of recombinant
      plasmids capable of complementing pyrF, argIF and proAB mutations in Escherichia
      coli.
AB  - Fragments of Aspergillus nidulans DNA obtained after digestion with EcoRI, BamHI
      and HindIII endonucleases were cloned in Escherichia coli in plasmid pBR322.
      These gene banks were used for transformation of 15 E. coli auxotrophic mutants
      and in 5 cases prototrophic clones containing recombinant plasmids were selected.
      Three different recombinant plasmids conferring prototrophy to pyrF, proAB and
      argIF mutants were analyzed. Hybridization experiments indicated that in two of
      these plasmids the inserted fragment of DNA hybridized not only to the A.
      nidulans but also to the E. coli DNA.

PMID- 19852108
TI  - Primary and secondary immune response to measles vaccine strain.
AB  - The rates of primary and secondary cell-mediated immune responses and their
      correlation with humoral responses were estimated. Cell-mediated reactions were
      evaluated by the leucocyte migration inhibition test. No significant differences
      were found in the intensity of primary and secondary cellular responses. The cell
      mediated response was not intensified by complete Freund adjuvant, which
      stimulated the humoral response. The kinetics of changes in cell-mediated
      reaction was comparable with that observed for other viruses.

PMID- 19852109
TI  - Separation and properties of polyhydric alcohol dehydrogenases from Mycobacterium
      sp. 279 and Mycobacterium phlei.
AB  - Glucose- or polyol-grown mycobacteria were disrupted by ultrasonication and cell
      free extracts fractionated with ammonium sulfate, Sephadex G-100 and DEAE
      cellulose chromatography. In various enzyme preparations, NAD-coupled polyol
      dehydrogenase activities were determined spectrophotometrically at 340 nm.
      Evidence is presented forthe occurrence of three types of enzymes called after
      the most active substrates: ribitol dehydrogenase, D-arabitol dehydrogenase and D
      sorbitol dehydrogenase. The enzymes have been separated, and characterized on the
      basis of their polyol specificity, molecular weight, heat resistance and pH
      stability. The dehydrogenation reaction was influenced by the kind of buffer and
      proceeded most rapidly with glycine/NaOH in a range of pH from about 9 (for
      glycerol, erythritol, and ribitol) to about 11 (for other polyols). Tris buffer
      was found to inhibit the reaction with polyhydric alcohols containing D-ribo or D
      xylo configuration. Km values for several polyols and Ki for Tris have been
      established.

PMID- 19852110
TI  - A mannoglucokinese of Mycobacterium tuberculosis H37Ra.
AB  - An ATP: D-glucose and D-mannose 6-phosphotransferase activity was found in
      Mycobacterium tuberculosis HERa. The activity was separated from other ATP- and
      polyphosphate D-glucose phosphotransferases in a procedure involving
      precipitation with ammonium sulfate, treatment with calcium phosphate gel, DEAE
      cellulose and DEAE-Sephadex A50 chromatography. The optimum pH of the
      phosphorylation reaction was from 9 to 10.5. The hexokinase phosphorylated D
      glucose with a Km of 20 mM under conditions of MgATP saturation. The Km for MgATP
      was 0.2 mM. The enzyme showed a higher activity on D-mannose at a saturation
      level being about 100-fold lower than that of D-glucose; it did not utilize
      either D-fructose or D-glucosamine. Inorganic poly(P) could not replace ATP as
      the phosphate donor. M. tuberculosis H37Ra was unable to grow on D-mannose which
      may suggest that the enzyme studied is involved in endogenous metabolism of this
      sugar.

PMID- 19852111
TI  - The effect of naphthylthiourea salts on the growth of acid-fast saprophytic
      bacilli.
AB  - SS'-naphthylisothiourea-1,4 and SS'-naphthylisothiourea-1,5 inhibit growth of
      acid-fast saprophytic bacilli. The lowest inhibitory concentration for the most
      sensitive strain, Mycobacterium smegmatis, is 1.562 microg/ml. These compounds
      act bacteriostatically on Mycobacterium sp. The growth of other investigated
      microorganisms was inhibited only at markedly higher concentrations.

PMID- 19852112
TI  - Studies on thiosulfate reduction by Desulfovibrio vulgaris.
AB  - Dissimilatory reduction of thiosulfate in a-glycerophosphate, lactate and
      pyruvate media has been studied. Simplified equations describing respiration of
      bacteria have been proposed on the ground of the established stoichiometry of the
      reduction process.

PMID- 19852113
TI  - Studies on the synthesis of basic proteins and antigenic components in measles
      virus infected cells.
AB  - The synthesis of histone f1 fraction in synchronous culture of (3H)-L-lysine
      labeled HeLa cells was inhibited 30 to 45 hours earlier and to a higher degree
      after infection with attenuated L-16 strain of the measles virus than after
      infection with laboratory Edmonston strain. Dithiothreitol and triton X-100 were
      used to isolate a cytoplasmatic component (K-2c) lacking infectivity but
      associated with hemagglutinating activity, from both strains. The component from
      both strain induced the synthesis of measles antibodies detected by the
      hemagglutination inhibition, neutralization and immunodiffusion techniques. The
      antibody titers in the sera of animals vaccinated with K-2c of L-16 strain were
      similar or higher than for K-2c of the Edmonston strain.

PMID- 19852114
TI  - Estimation of antibodies to human cytomegalovirus by immunofluorescence and
      radioimmunoassay.
AB  - The 125J labeled IgG fraction against rabbit IgG of goat origin was employed for
      the detection of CMV IgG and IgM antibodies in the double indirect
      radioimmunoassay. The results were compared with those obtained in complement
      fixation, indirect immunofluorescence and anti-complement immunofluorescence
      tests. The application of labeled anti-fc antisera, instead of antisera against
      whole IgG in the tests for detection of specific CMV IgG antibody resulted in
      increased sensitivity of radioimmunoassay and reduction of non-specific
      cytoplasmatic reactions in preparations stained by indirect immunofluorescence.
      The absorption of sera with protein A rich staphylococci and aggregates to
      immunoglobulin eliminated unwanted secondary IgM staining caused by rheumatoid
      factors both in indirect immunofluorescence and radioimmunoassay tests for CMV
      antibodies.

PMID- 19852115
TI  - The lethal effects of some onolophosphate insecticides on yeast Saccharomyces
      cerevisiae.
AB  - Thre enolophosphate insecticides (chlorphenvinphos: 0-/-/2',4'-dichlorophenyl/-2
      chlorovinyl/diethyl phosphate, bromphenvinphos: 0-/1-/2',4'-dichlorophenyl/-2
      bromovinyl/diethyl phosphate, mebromvinphos: 0-/1-/2',4'-dichlorophenyl/-2
      bromovinyl/dimethyl phosphate) have been tested for their biological activity in
      baker's yeast. The results indicate that the chemicals exert an immediate
      hibitory effect on amino acid transport system, respiration, fermentation and ell
      growth. Consequently the effect of precipitous cell death also occurred.
      Furthermore the direct destroying action of the studied chemicals on protoplast
      as also observed. The main cause of cell death is the development of membrane
      leakiness. It was found that the loss of sugar transport activity parallels the
      loss of cell viability. All the studied insecticides showed negligible netic
      activity.

PMID- 19852116
TI  - Starch contents in alfalfa nodules with effective and ineffective symbiotic
      responses.
AB  - Rhizobium meliloti auxotrophic and ineffective mutants induced nodules
      containing: 9.35 microg of starch per mg of the plant tissue (wet wt.) in the
      case of strain his-240 which did not occupy host cells and 2.7 to 3.5 microg of
      starch in strains: arg-55, cys-243, cys-244 and cys-246 which occupied part of
      the host cells (bacteroidal zone). Nodules induced by prototrophic and effective
      strains i.e. L5-30 (wilde type) and prototrophic transductants of arg-55 and his
      240 mutants contained 0.13 to 0.06 microg of starch per mg of the plant tissue
      (wet wt.). These results indicate that iodometric estimation of starch contents
      in the nodules may by used as a simple test showing the quantity of plant cells
      infected by rhizobia.

PMID- 19852117
TI  - Intracellular localization of the ATP-dependent deoxyribonuclease of Caulobacter
      crescentus.

PMID- 19852118
TI  - The filler revolution: a six-year retrospective.
AB  - There are currently more than 20 FDA-approved fillers in the United States
      (U.S.), noteworthy considering that it was only six years ago that the first
      hyaluronic acid filler was approved. The pace of development of filler substances
      in the last few years has been extremely rapid. The authors review the
      development, advantages, and disadvantages of fillers currently available in the
      U.S.

PMID- 19852119
TI  - Treatment of severe alopecia areata with intralesional steroid injections.
AB  - BACKGROUND: Treatment of alopecia areata with intralesional steroid injection is
      generally recommended for people who have less than 50% scalp involvement. In a
      specialized hair loss clinic, the authors successfully treated patients with
      extensive alopecia areata (over 50% but under 99%) with intralesional
      corticosteroid injections. OBSERVATIONS: A review of patients with extensive
      alopecia areata was done. Six out of 10 patients responded to treatment with
      intralesional triamcinolone acetonide. In comparison to the non-responders, the
      responders tended to have exclamation mark hairs and a positive hair pull test at
      their initial physical examination, and exhibited improvement during the initial
      months of treatment. Complications were negligible, with mild reversible atrophy
      in three patients. The treatment was well tolerated and, in some patients, pain
      was minimized by use of a topical anesthetic agent applied under occlusion prior
      to the visit. CONCLUSION: Intralesional triamcinolone acetonide is a safe and
      effective treatment for patients with extensive alopecia areata. Patients with
      exclamation point hairs and a positive hair pull test may be more likely to
      respond.

PMID- 19852120
TI  - Cost effectiveness of Mohs micrographic surgery: review of the literature.
AB  - BACKGROUND: A number of treatment modalities are currently in existence for non
      melanoma skin cancer, including microscopically controlled surgical excision
      (e.g., Mohs micrographic surgery [MMS]), traditional surgical excision, radiation
      therapy, electrodessication and curettage, cryosurgery, photodynamic therapy and
      topical chemotherapeutic agents. MMS has the significant advantage of the lower
      recurrence rates of all treatment modalities, where five-year cure rates for MMS
      for primary BCCs are 1% relative to surgical excision (10.1%), electrodessication
      and curettage (7.7%), radiation therapy (8.7%) and cryotherapy (7.5%). Previous
      studies have also indicated, across specialties, that dermatologists have the
      highest rates for complete removal of non melanoma skin cancer (NMSC) which are
      significantly greater than those for otolaryngologists (P>0.02) and plastic
      surgeons (P<0.0008). OBJECTIVE: To evaluate and compare the results of recent
      studies comparing the cost effectiveness of MMS to other treatment modalities
      performed by dermatologists and other physicians performing treatment of NMSC
      (otolaryngologic (ENT) surgeons, plastic surgeons, general surgeons). RESULTS:
      MMS is equivalent in cost to excision with permanent sections, 12% less costly
      than office based excision with frozen sections and 27% less costly than excision
      with frozen sections in an ambulatory surgical center (ASC). The most significant
      difference between MMS and surgical excision was the facility fee of excision
      with frozen sections in an ASC, (differential of $443-$555). With surgical
      excision, 32-39% of cases require a second procedure for clear margins.
      Additionally, with subsequent procedures for surgical excision cases, there is
      likely a greater volume of tissue removed and ramifications on functional
      preservation and cosmesis, which are difficult to quantify. CONCLUSION: Analysis
      of the existing literature on MMS relative to surgical excision confirms the
      value of MMS in both obtaining the highest initial cure rates and lowest
      recurrence rates. This analysis confirms that MMS is a cost effective treatment,
      which is lower in cost than surgical excision, which often includes an ASC
      facility fee and a subsequent re-excision procedure. Cost effectiveness analysis
      demonstrating the outcomes based efficiency of MMS are critical in the current
      health care climate with heightened sensitivity to financial pressures and
      declining reimbursement rates which may challenge our ability to provide patients
      with the optimal treatment for NMSC.

PMID- 19852121
TI  - A single-center dose-comparison study of botulinum neurotoxin type A in females
      with upper facial rhytids: assessing patients' perception of treatment outcomes.
AB  - BACKGROUND: Few studies evaluate patient-reported outcomes (PROs). OBJECTIVES: To
      assess the PROs of treatment with botulinum neurotoxin type A (BoNTA) in upper
      facial lines; to evaluate two new PRO instruments. METHODS: Prospective,
      randomized, double-blind study of 32 U, 64 U, or 96 U BoNTA divided among 16
      sites. Measurements included the Facial Line Outcomes (FLO-11) Questionnaire
      version 1.0 and the Self-Perception of Age (SPA) measure version 2.0. RESULTS:
      Sixty females, mean age 42 +/- 8.7 years, were enrolled. Significant improvements
      (P<0.01) in mean FLO-11 scores occurred by week 2 for all groups and remained
      significant through week 16 for all groups except the 32-U group. Approximately
      45-60% of the patients reported looking younger by a mean of 3.6-5.8 years.
      CONCLUSION: BoNTA treatment resulted in desired relaxed and younger appearance,
      as measured by the FLO-11 Questionnaire and the SPA measure.

PMID- 19852122
TI  - A stabilized 0.1% retinol facial moisturizer improves the appearance of
      photodamaged skin in an eight-week, double-blind, vehicle-controlled study.
AB  - Retinol is a cosmetic ingredient that is structurally similar to all-trans
      retinoic acid, which has been shown to be effective in the treatment of
      photodamage. Since skin keratinocytes are reported to metabolize retinol to
      retinoic acid, investigators have hypothesized that retinol may also be helpful
      in improving skin photodamage. In this eight-week, double-blind, split-face,
      randomized clinical study, a stabilized 0.1% retinol-containing moisturizer was
      tested (36 subjects) against the vehicle (28 subjects) in women with moderate
      facial photodamage. Each product was applied once daily to the designated half
      side of the face. Subjects were evaluated at baseline and after four and eight
      weeks of treatment using a 0-9 scale for photoaging parameters. The results
      showed that, after eight weeks, the retinol moisturizer was significantly more
      efficacious than the vehicle in improving lines and wrinkles, pigmentation,
      elasticity, firmness and overall photodamage. Many of these differences were
      significant at week 4, with a progressive improvement to week 8. This study
      demonstrates that a formulation containing stabilized retinol is safe and
      effective to ameliorate the appearance of photoaged skin.

PMID- 19852123
TI  - Treatment of aging neck with Lipostabil Endovena.
AB  - BACKGROUND: The lower third of the face and neck have distinct changes that occur
      with aging: the lost of the perfect jaw line due to laxicity of skin and fat
      deposits associated with "turkey neck." Theses changes can be globally and
      drastically addressed with traditional rhytidectomy, however patients
      increasingly seek less invasive procedures. Injections with Lipostabil Endovena-a
      mixture of phosphatidylcholine and deoxycholate, a bile salt-have been used to
      reduce unwanted, accumulated fat. Recent in vivo investigations indicate that
      phosphatidylcholine and deoxycholate cause adipocyte lysis, an inflammatory
      processes and fibrosis. These reactions lead to skin retraction. OBJECTIVE: This
      paper reports the author's experience treating aging neck using Lipostabil
      Endovena. RESULTS: Laxity of the skin improved in all patients. A marked
      reduction in double chins was noted and the jaw line was reconstructed. Adverse
      effects, including transient burning, erythema and local swelling were present in
      all patients, but resolved themselves without intervention. CONCLUSION: The
      author's clinical experience supports the conclusion that Lipostabil Endovena
      treats subcutaneous fat tissue and that fibrosis after the inflammatory process
      retracts the skin, tightening the injected area and improving the aging neck.

PMID- 19852124
TI  - Successful treatment of pemphigus vulgaris with etanercept in four patients.
AB  - Pemphigus vulgaris is an autoimmune disease characterized by intraepidermal
      blister formation. The treatment of pemphigus vulgaris is generally regarded as
      difficult. Corticosteroids, the drug class of first choice, often must be
      combined with steroid-sparing agents to prevent hazardous, long-term side
      effects. The authors describe four patients with severe pemphigus vulgaris who
      were treated with the tumor necrosis factor (TNF)-alpha antagonist, etanercept,
      twice weekly. In all four cases, the addition of etanercept produced dramatic
      clinical improvement and facilitated the reduction of corticosteroids necessary
      to maintain symptom control. Thus, etanercept may be an effective therapeutic
      agent for pemphigus vulgaris and should be considered as an alternative treatment
      option for patients presenting with recalcitrant disease.

PMID- 19852125
TI  - Incontinentia pigmenti: treatment of IP with topical tacrolimus.
AB  - Incontinentia pigmenti (IP), or Bloch-Sulzberger syndrome, is a rare X-linked
      dominant genodermatosis primarily affecting females. Although IP affects many
      organ systems, the hallmark feature of this disease is its characteristic
      cutaneous eruption along the lines of Blaschko that evolves through four distinct
      stages: inflammatory/vesiculobullous, verrucous, hyperpigmented and
      hypopigmented/ atrophic. We describe a case of IP in its vesicular stage that
      completely resolved with topical Protopic (tacrolimus) 0.1% ointment. The
      treatment successfully halted the progression of disease through its subsequent
      disfiguring stages.

PMID- 19852126
TI  - The combined use of forced cold air and topical anesthetic cream for analgesia
      during the treatment of palmar hyperhydrosis with botulinum toxin injections.
AB  - BACKGROUND: Palmar hyperhidrosis is an uncomfortable condition that can severely
      affect a patient's quality of life. Injections of botulinum toxin have proven to
      be an efficient treatment modality, however the pain associated with palmar
      injections has limited the use of this therapy. OBJECTIVE: The authors describe a
      novel method of analgesia combining topical analgesic cream and forced cold air
      during botulinum injection treatment of palmar hyperhidrosis. CASE REPORT: This
      is a case report of a patient with a 10-year history of palmar hyperhidrosis.
      Both hands were pretreated with topical anesthetic cream and the right hand was
      additionally treated with forced cold air at a distance of 1 cm for up to 30
      seconds before injection administration. After the botulinum injection was
      administered to both hands, the patient was subjectively asked about pain during
      injection. RESULTS: The patient subjectively reported a 75% decrease in the
      intensity of pain with the combination use of topical anesthetic cream and forced
      cold air, which she said made the injections more tolerable. No epidermal changes
      were noted at the time of treatment or at follow-up. CONCLUSION: The use of
      botulinum toxin for the treatment of palmar hyperhidrosis is limited due to the
      pain associated with injections of the palm. In this case report, we describe the
      successful use of forced cold air with topical anesthetic cream to lessen the
      pain of botulinum toxin injections during the treatment of hyperhidrosis.

PMID- 19852127
TI  - Delayed onset nodules from liquid injectable silicone: report of a case,
      evaluation of associated histopathology and results of treatment with minocycline
      and celocoxib.
AB  - Although liquid injectable silicone is safe for the majority of patients treated,
      there are a few individuals for whom this treatment has been problematic. The
      problems that arise include migration and granuloma formation. In some instances
      the granulomas may arise years after the injections. Treatment of these
      granulomas typically involves the use of steroids. However, the complications
      associated with long-term steroid usage, as well as the limited efficacy in some
      patients, have prompted clinicians to seek alternative treatments. This article
      presents the case of a woman who had delayed granuloma formation to liquid
      injectable silicone treated with a combination of minocycline and celocoxib. The
      histology of this case, as well as potential mechanisms of action for the
      treatment, are also presented.

PMID- 19852128
TI  - Nanotechnology in cosmetics and sunscreens: an update.

PMID- 19852129
TI  - Unexplained agglutination of stored red blood cells in Alsever's solution caused
      by the gram-negative bacterium Serratia liquefaciens.
AB  - Alsever's solution has been used for decades as a preservative solution for
      storage of RBCs. From October 2005 to January 2006, unexplained hemagglutination
      of approximately 10 to 20 percent of RBCs stored for several days in a modified
      version of Alsever's solution was noticed in quality control testing at the
      Canadian Blood Services Serology Laboratory. An investigation, including
      microbial testing, was initiated to determine the cause of the unexplained
      hemagglutination. The gram-negative bacterium Serratia liquefaciens was isolated
      from supernatant solutions of agglutinated RBCs. Further characterization of this
      strain revealed that it has the ability to form biofilms; presents high levels of
      resistance to chloramphenicol, neomycin, and gentamicin; and causes mannose
      sensitive hemagglutination. The source of S. liquefaciens contamination in RBC
      supernatants was not found. However, this bacterium has not been isolated since
      January 2006 after enhanced cleaning practices were implemented in the serology
      laboratory where the RBCs are stored. This biofilm-forming, antibiotic-resistant
      S. liquefaciens strain could be directly linked to the unexplained
      hemagglutination observed in stored RBCs.

PMID- 19852130
TI  - Hyperhemolytic transfusion reaction attributable to anti-Fy3 in a patient with
      sickle cell disease.
AB  - A case of hyperhemolytic transfusion reaction attributable to anti-Fy3 in a 30
      year-oldAfricanAmerican woman with a history of sickle cell disease is reported.
      The patient was admitted for vaso-occlusive sickle cell crisis and received 4
      units of packed RBCs secondary to worsening symptomatic anemia (Hb 5.0 g/dL). On
      admission, the patient's antibody screen and identification showed anti-V and
      anti-E, and her antibody history included anti-E,-C,-Jk(b),-N, -V,-S,-Sl(a), and
      a cold agglutinin with possible anti-I specificity. A DAT performed on her RBCs
      was negative. RBC units that lacked E, C, Jk(b), N,V, and S were transfused.
      Posttransfusion Hb was 8.9 g/dL. On day 10 she developed a fever of 103 degrees
      F, and on day 11 her Hb decreased to 6.4 g/dL. She complained of severe back pain
      and dark urine. In addition, she became hypertensive, tachycardic, and jaundiced.
      The DAT indicated the presence of IgG on the patient's RBCs. Anti-Fy3 was
      identified in the serum and eluate. During the next 24 hours, her Hb decreased to
      2.4 g/dL. The LDH level was 1687 U/L, and her reticulocyte count was 2.6%. A
      delayed hemolytic transfusion reaction with hyperhemolysis secondary to anti-Fy3
      was suspected and was successfully treated with IVIG and high-dose prednisone. To
      the best of our knowledge, this is the first published case of hyperhemolysis in
      sickle cell disease attributable to anti-Fy3.

PMID- 19852131
TI  - Managing a pregnancy with antibodies: a clinician's perspective.

PMID- 19852132
TI  - Antibodies to Le(a) and Le(b): a challenge to identify regardless of how you
      detect them.

PMID- 19852133
TI  - 2008 Immunohematology Reference Laboratory Conference. Summary of presentations.

PMID- 19852134
TI  - The bottom line: students must be engaged.

PMID- 19852135
TI  - Merging departments: dealing with the good, the bad, and the ugly.

PMID- 19852136
TI  - Online mentoring through MentorNet.net.

PMID- 19852137
TI  - Natural selection and national trends in mitral repair.

PMID- 19852138
TI  - Trends in mitral valve surgery: a single practice experience.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral repair has evolved to a point where three
      methods can be used to address most pathologies: full ring annuloplasty (RA) for
      annular disease; Gore-Tex artificial chordal replacement (ACR) for chordal
      disease; and autologous pericardial augmentation (PA) for leaflet disease. The
      study aim was to assess the impact of the increasing application of these methods
      on operative results over time. METHODS: Of 328 consecutive mitral valve
      procedures, 34% involved myxomatous prolapse, 23% rheumatic, 13% ischemic, 12%
      pure annular dilatation, 7% prosthetic dysfunction, 6% endocarditis, 3%
      hypertrophic obstructive cardiomyopathy (HOCM), and 2% 'other'. All patients
      underwent RA. Myxomatous prolapse was repaired with ACR, and ischemic and annular
      dilatation with RA alone. Rheumatic, endocarditis, and HOCM etiologies were
      repaired with all three methods. Patients were allocated to two-year increments,
      and also to repair versus replacement groups. Operative outcomes over time were
      assessed with linear and binomial regression. RESULTS: Overall, 66% of mitral
      valves were repaired; the average operative mortality was 6% (2% for repair, 7%
      for replacement), and 18% involved multiple valve procedures (mortality 16%). The
      extent of repair increased over time, from 55% to 100% of all etiologies. Over
      the same period, operative mortality fell from 6% in 1994 to 0% over the past six
      years. Other variables, such as age, presentation status, left ventricular
      dysfunction and etiology were relatively constant over the period. Reoperation
      rates after repair have been only 2% over the past 10 years of follow up.
      CONCLUSION: With recent innovations, most mitral disease can be repaired with
      combinations of RA, ACR and PA. Today, operative mortality is approaching zero,
      and one factor may be the increasing application of repair to all mitral
      pathologies. These data support the trend of expanding valve repair across most
      mitral disorders.

PMID- 19852139
TI  - Aortic valve-in-valve implantation: impact of transcatheter- bioprosthesis size
      mismatch.
AB  - BACKGROUND AND AIM OF THE STUDY: Transcatheter aortic valves (TAVs) provide
      minimally invasive treatment for high-risk patients with severe native aortic
      stenosis. While the off-label application of TAV for degenerative bioprosthetic
      stenosis (valve-in-valve therapy) is attractive, few cases have been reported. If
      the rigid annulus and stent posts of bioprostheses prevent full expansion of the
      TAV, the hemodynamic performance may be compromised. The study aim was to
      evaluate the use of a 23 mm TAV within normal bioprostheses of equivalent or
      smaller orifice sizes. METHODS: Twelve TAVs designed to mimic the 23 mm Edwards
      SAPIEN valve were created using stainless steel stents and trileaflet pericardial
      valves. A custom-built pulse duplicator was used to measure the hemodynamic
      performance of the TAV within 19, 21 and 23 mm Edwards pericardial
      bioprostlieses. The transvalvular gradient, effective orifice area (EOA) and
      regurgitant volume were used to evaluate valve-in-valve therapy for each valve
      size. RESULTS: The TAV demonstrated similar hemodynamics to the Edwards SAPIEN
      valve (mean pressure gradient 6.68 +/- 2.11 mmHg and EOA 2.07 +/- 0.35 cm2).
      Acceptable valve-in-valve hemodynamics were achieved only in the 23 mm
      bioprosthesis after TAV implantation, with no significant change in mean pressure
      gradient (5.93 +/- 0.87 to 8.27 +/- 1.19 mmHg, p = 0.052) and EOA (2.13 +/- 0.15
      to 1.79 +/- 0.15 cm2, p = 0.053). In 19 and 21 mm valves, the excess pericardial
      tissue relative to the stent EOA resulted in severe and moderate stenosis,
      respectively. The mean pressure gradient increased from 16.18 +/- 2.20 mmHg to
      45.53 +/- 12.54 mmHg (p = 0.004) in 19 mm bioprostheses, and from 11.84 +/- 1.88
      mmHg to 28.18 +/- 9.03 mmHg (p = 0.004) in 21 mm bioprostheses. Furthermore, the
      EOA was reduced from 1.28 +/- 0.1 to 0.78 +/- 0.11 cm2 (p < 0.001) in 19 mm
      valves, and from 1.51 +/- 0.15 to 1.01 +/- 0.19 cm2 (p < 0.001) in 21 mm
      bioprostheses. The TAV resulted in an increased regurgitant volume for all valve
      sizes. CONCLUSION: Oversized TAVs are constrained by rigid bioprostheses,
      creating hemodynamic complications. Patients with 19 and 21 mm Edwards
      pericardial bioprostheses may be poor candidates for valve-in-valve therapy with
      the currently available technology.

PMID- 19852140
TI  - Pulmonary function and immediate outcome of patients undergoing aortic valve
      replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate whether pulmonary
      function, as assessed by spirometry, affects immediate outcome after aortic valve
      replacement (AVR). METHODS: Data relating to the preoperative percentages of
      predicted forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)
      were retrieved from a series of 453 patients who underwent AVR, with or without
      coronary artery bypass surgery. RESULTS: The percentage of predictive FVC (odds
      ratio (OR) 0.952; 95% CI 0.914-0.990; AUC 0.749; p = 0.019), but not of predicted
      FEV1, nor any history of pulmonary disease, proved to be independent predictors
      of in-hospital mortality, even when adjusted for the logistic EuroSCORE. A
      percentage predictive FVC of < 80% proved to be the best cut-off (in-hospital
      mortality 6.3% versus 1.3%; p = 0.005; OR 5.100; 95% CI 1.544-16.849; specificity
      69%, sensitivity 69%). The percentage of predictive FVC was found to be an
      independent predictor of stroke (OR 0.956; 95% CI 0.923-0.989; p = 0.009).
      Patients with a percentage of predictive FVC < 80% had a risk of postoperative
      stroke of 6.9% versus 1.9% among those patients with better FVC values (OR 3.769;
      95% CI 1.342-10.581; p = 0.012). Patients with a percentage of predictive FVC <
      80% (10.4% versus 4.2%; OR 2.648; 95% CI 1.225-5.724; p = 0.011) and a history of
      pulmonary disease (13.1% versus 5.1%; OR 2.808; 95% CI 1.117-6.694; p = 0.016)
      had a significantly higher risk of an intensive care unit stay of five or more
      days. Postoperative pneumonia was not associated with either spirometric
      parameters, nor with any history of pulmonary disease. CONCLUSION: Pulmonary
      disease, as indicated by decreased preoperative values of FVC and FEV1, is an
      important comorbidity factor in patients undergoing AVR surgery. Further studies
      are required to demonstrate whether the identification and treatment of these
      patients could improve their outcome after AVR.

PMID- 19852141
TI  - The role of the sinuses of Valsalva in aortic root flow dynamics and aortic root
      surgery: evaluation by magnetic resonance imaging.
AB  - BACKGROUND AND AIM OF THE STUDY: Combined replacement of the aortic valve and
      ascending aorta using a composite graft represents the standard treatment for
      dilated aortic root with concomitant structural damage of the aortic valve,
      especially when the aortic valve cannot be preserved. Unfortunately, hemodynamic
      changes associated with prosthetic replacement of the aortic root have not been
      fully elucidated. The study aim was to compare hemodynamics within the replaced
      aortic root using either a prosthetic vascular graft with bulges mimicking the
      sinuses of Valsalva and including a stented pericardial valve, or a straight
      xenopericardial conduit and a stentless porcine valve. METHODS: Between July 2004
      and March 2006, a total of 35 patients (mean age 65.2 years: range: 32-80 years)
      was enrolled into the present study. Aortic root replacement was performed in
      nine patients with a Valsalva graft (Gelweave Valsalva; Vascutek, Renfrewshire,
      UK) including a stented pericardial valve, and in 19 patients with a
      xenopericardial conduit containing a stentless porcine valve. All patients
      underwent postoperative magnetic resonance imaging (MRI). A control group of
      seven patients allowed for comparison with native aortic root hemodynamics.
      RESULTS: Maximum flow-velocity above the aortic valve as one marker of compliance
      of the aortic root was slightly higher in patients with a Valsalva graft compared
      to native aortic roots (1.9 m/s versus 1.3 m/s, p = 0.001), but was significantly
      lower than in patients with the xenopericardial graft without neo-sinuses (1.3
      m/s versus 2.4 m/s, p < 0.001). CONCLUSION: The pre-shaped bulges in the
      prosthetic Valsalva graft effectively mimic the native sinuses of Valsalva,
      improve compliance of the aortic root, and result in a more physiologic flow
      pattern, as demonstrated by postoperative MRI.

PMID- 19852142
TI  - Infective endocarditis: a continuous challenge. The recent experience of a
      European tertiary center.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to monitor infective
      endocarditis (IE) before and after the condition was brought into focus in
      hospitals in the Aarhus region of Denmark. METHODS: A total of 172 patients with
      IE, all of whom had been referred to the regional tertiary center during 2000
      2001 or during 2005-2006, was included prospectively into the study. RESULTS:
      Between 2000-1 (n = 51) and 2005-6 (n = 121), a very large (137%) increase
      occurred in the number of IE patients referred (p < 0.01). Yet, over this period,
      the delay from onset of symptoms to admission remained at one month, with a
      further prolongation of one week (p < 0.05) in 40% of patients who had received
      pre-hospital antibiotic treatment. A previous healthcare procedure was recorded
      in 37% of cases, with an ascending trend from 2000-1 to 2005-6. The increase in
      six-month mortality was high, from 16% to 26%, but was not statistically
      significant. Independent predictors were prosthetic valve IE (p = 0.02), advanced
      age (p = 0.03) and co-morbidity (p = 0.05); all three of these features increased
      over the five-year study interval. CONCLUSION: Although increased regional
      hospital attention to IE seemed to facilitate admission to the authors' center,
      this did not improve survival, apparently because of an unchanged admission delay
      and increasing age, comorbidity, and prosthetic valve IE. Delayed admission and
      health care-induced IE were susceptible to modification. Future measures should,
      therefore, be particularly focused on high-risk patients, on educating the
      general practitioners, and on improving access to primary healthcare facilities
      for blood culture and echocardiography.

PMID- 19852143
TI  - Infective endocarditis in the Czech Republic: eight years of experience at one of
      the country's largest medical centers.
AB  - BACKGROUND AND AIM OF THE STUDY: Limited data have been reported that
      characterize infective endocarditis (IE) in the Czech Republic. Hence, some local
      cases of IE were examined to provide a current profile of the disease in Central
      Europe. METHODS: A descriptive case series of IE patients seen on all internal
      medicine services of a major teaching institution in the Czech Republic over an
      eight-year period was developed. RESULTS: Prosthetic valves and rheumatic
      carditis were the underlying predisposing conditions in 18% and 17%,
      respectively, of all IE episodes. Staphylococcal species were the most common
      pathogens identified, and were present in 45% of IE episodes. In contrast,
      streptococcal species were recovered in only 14% of episodes. The proportion of
      culture-negative endocarditis cases was sizable (18%). The aortic valve was most
      commonly involved in IE episodes (47%), followed by the mitral valve (33%). The
      in-hospital mortality rate was 21%. CONCLUSION: Younger patients, the occurrence
      of underlying rheumatic carditis, a lack of injection drug use, and an increased
      frequency of culture-negative infections are unique IE characteristics among
      Czech patients, as compared to those seen in patients from Western Europe and the
      United States. The heralded microbiological shift from viridans group
      streptococci to Staphylococcus aureus may apply to the current study.

PMID- 19852144
TI  - Non-typhoid Salmonellae and prosthetic valve endocarditis: more than a rare
      coincidence? A review of the literature.
AB  - Non-typhoid Salmonellae (NTS) commonly cause gastroenteritis but are rarely found
      pathogens in prosthetic heart valve endocarditis. The details of two patients
      from the authors' institution and 15 published cases are reviewed in terms of
      their risk factors, clinical findings and outcomes. Only two of eight patients
      with paravalvular leakage or abscess--the most serious local complications-
      survived, both with surgery. It appears that NTS bacteremia in patients with
      prosthetic valves and concomitant risk factors should be treated early with high
      dose antimicrobials for up to six weeks in order to minimize the risk of
      endocarditis.

PMID- 19852145
TI  - Pathogen burden in degenerative aortic valves is associated with inflammatory and
      immune reactions.
AB  - BACKGROUND AND AIM OF THE STUDY: The presence of five pathogens was assessed,
      together with a possible correlation of the total pathogen burden on inflammation
      and (auto)immunity in aortic stenosis (AS) and degenerative aortic valve
      bioprosthesis (BP). METHODS: Diseased valve specimens from a total of 68 patients
      (52 with AS, 16 with BP) were studied. The presence and localization was assessed
      of Chlamydia pneumoniae (cHSP60), Helicobacter pylori (HP), cytomegalovirus
      (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV), as well as of
      macrophages (CD68), C-reactive protein (CRP) and human heat shock protein 60
      (hHSP60), by using immunohistochemical and morphometric analyses. RESULTS: In the
      majority of degenerative aortic valves, specific pathogens, inflammation and
      immunity were localized predominantly in the fibrosa of AS patients, and in
      superficial regions of the BP. The categorization of valves as having four or
      more pathogens (n = 37) or fewer pathogens (n = 31) demonstrated an increased
      signaling of CD68 (p = 0.03) and CRP (p = 0.02). Specifically, cHSP60, HP and
      hHSP60 levels were increased in valves where one or two bacteria were identified
      (n = 59) compared to those without bacterial presence (n = 9) (p = 0.04).
      CONCLUSION: The pathogen burden may contribute to valvular degeneration by
      promoting further deleterious inflammatory and (auto)immune processes at the
      level of the valvular fibrosa.

PMID- 19852146
TI  - Extracorporeal support in a patient with cardiogenic shock due to Aerococcus
      urinae endocarditis.
AB  - Aerococcus urinae is a newly identified Gram-positive coccus that causes serious
      infections. To date, only 15 cases of A. urinae infective endocarditis have been
      reported, but with a very high mortality. The case is reported of a patient with
      A. urinae double valve endocarditis. Following aortic and mitral valve
      replacement, the patient suffered from refractory cardiogenic shock;
      extracorporeal membrane oxygenation was used successfully as a rescue mechanical
      support.

PMID- 19852147
TI  - Interstitial cells from left-sided heart valves display more calcification
      potential than from right-sided valves: an in-vitro study of porcine valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The calcification of cardiac valves is more
      frequently observed on left-sided (aortic or mitral) than right-sided (pulmonic
      or tricuspid) valves. The cause of this preferential left-sided calcification
      remains relatively unknown. The study aim was to evaluate the capacity of
      interstitial cells isolated from the four cardiac valves of healthy adult pigs to
      calcify in culture. METHODS: Interstitial cells were isolated from the valve
      leaflets of three healthy young pigs and cultured in DMEM/fetal bovine serum
      (10%) in the presence or absence of osteogenic additives (ascorbic acid,
      dexamethasone, beta-glycerophosphate). RESULTS: The proliferation rate was
      similar for cells from each of the four valves. After longer periods of culture
      (> 10 days), cells from each valve spontaneously formed several calcification
      nodules, the process being accelerated in the presence of osteogenic additives
      (to 4-7 days). Alkaline phosphatase (AP) activity was highest in cells
      originating from the aortic and mitral valves, respectively, and least in those
      from the pulmonic and tricuspid valves. Culture with the osteogenic additives
      increased the AP activity by at least 50% for each valve, but the relative AP
      activity between cells from each valve origin tended to remain similar (aortic >
      mitral > pulmonic > tricuspid). Interestingly, the levels of matrix Gla-protein
      mRNA (an endogenous calcification inhibitor) followed an opposite trend of
      expression for each valve. CONCLUSION: Interstitial cells from porcine cardiac
      valves share similarities, although the capacity to calcify is more evident in
      cells from valves of the left side of the heart. Interstitial cells from the
      aortic valve displayed the greatest potential for calcification.

PMID- 19852148
TI  - Valvular calcification and its relationship to atherosclerosis in chronic kidney
      disease.
AB  - BACKGROUND AND AIM OF THE STUDY: Cardiovascular calcification is a common
      complication in patients with chronic kidney disease (CKD). The study aim was to
      identify the characteristics and risk factors of valvular calcification, and its
      relationship to atherosclerosis, in CKD. METHODS: In this cross-sectional study,
      a total of 135 patients with CKD (mean age 52 +/- 11 years) included 58 pre
      dialysis patients, 36 dialysis patients, and 41 renal transplant recipients. A
      control group of 58 subjects was also examined. The characteristics of valvular
      calcification were assessed using transthoracic echocardiography. RESULTS: The
      combined prevalences of mitral or aortic valve calcification were 31% in pre
      dialysis patients, 50% in dialysis patients, 29% in renal transplant recipients,
      and 12% in controls (p = 0.001). The prevalences of mitral annular calcification
      were 17%, 31%, 27% and 2%, respectively (p = 0.001). In multivariate analysis,
      the risk factors for valvular calcification in CKD were age, duration of dialysis
      treatment and interleukin-6 level. Mitral annular calcification proved to be five
      fold more common in diabetic patients than among non-diabetics. A close
      association between valvular calcification and patients with or without increased
      carotid intima-media thickness (44% versus 15%, p < 0.001), carotid plaque (77%
      versus 49%, p = 0.002), calcified carotid plaque (65% versus 26%, p = 0.001),
      coronary artery disease (40% versus 15%, p = 0.003) and peripheral arterial
      disease (46% versus 9%, p < 0.001) was found. CONCLUSION: Valvular calcification
      is common in CKD, and is closely associated with findings of intimal arterial
      disease. The presence of inflammation and the duration of dialysis treatment
      contribute to this complication. Diabetes is also a prominent risk factor for
      mitral annular calcification in CKD.

PMID- 19852149
TI  - Immunoblot detection of soluble protein antigens from sodium dodecyl sulfate- and
      sodium deoxycholate-treated candidate bioscaffold tissues.
AB  - BACKGROUND AND AIMS OF THE STUDY: The detergent-based 'decellularization' of
      xenogeneic tissues is one approach to scaffolding a tissue-engineered heart valve
      construct; however, concern persists regarding the immunogenicity of
      decellularized xenogeneic bioscaffolds. The study aims were to: (i) develop a
      sensitive and robust immunoblot-based assay for the detection of soluble protein
      antigens in xenogeneic bioscaffolds; and (ii) evaluate the completeness of
      protein antigen removal from sodium dodecyl sulfate (SDS)- or sodium deoxycholate
      (SD)-treated bovine pericardium (BP) or porcine aortic valve (PAV) conduit.
      METHODS: Homogenized BP or PAV were injected into rabbits to generate immune
      serum towards these tissues. Soluble proteins were extracted from untreated BP
      and PAV. Immunoblot analyses of the extracts were performed using pre-immune and
      14-, 28-, 42-, 56- and 70-day post-immune serum. BP and PAV were treated
      sequentially with 4 h hypotonic lysis; with 0, 0.01, 0.025, 0.05, 0.1, 0.25 or
      0.5% SDS or SD for 24 h; and with 96 h of aqueous wash-out. Immunoblot analyses
      of protein extracts from treated tissues were performed using 70-day post-immune
      rabbit serum. RESULTS: Immunoblot analysis of untreated BP or PAV with pre-immune
      serum showed no immune banding. The immune banding density increased
      progressively when immunoblots were performed with 14-day through 70-day post
      immune serum. The immunoblot analysis of treated BP and PAV showed that soluble
      protein antigen removal from SDS- or SD-treated tissues was incomplete.
      CONCLUSION: Immunoblot analysis is a sensitive and robust assay for detecting
      soluble protein xenogeneic antigens after the decellularization of xenogeneic
      bioscaffolds. Under the study conditions, hypotonic lysis, SDS or SD detergent
      treatment, and aqueous wash-out-based decellularization of bovine pericardium and
      porcine aortic valve conduit did not completely remove detectable protein
      antigens.

PMID- 19852151
TI  - Four decades with a Starr-Edwards ball valve in the aortic position.
AB  - As the first reliable prosthetic heart valve to be introduced, the Starr-Edwards
      ball valve prosthesis has gained worldwide clinical acceptance. Although very few
      instances have been described of valve durability exceeding 30 years, the case is
      reported of a patient with a well-functioning Starr-Edwards ball valve prosthesis
      in the aortic position, 43 years after implantation.

PMID- 19852150
TI  - Fifteen years' single-center experience with the ATS bileaflet valve.
AB  - BACKGROUND AND AIM OF THE STUDY: Since its introduction in May 1992, the
      bileaflet ATS Open Pivot valve has been implanted routinely at the authors'
      institution. The study aim was to analyze, retrospectively, the 15-year clinical
      results of these implanted ATS valves. METHODS: Between May 1992 and December
      2005, a total of 1,160 ATS valves (749 aortic, 381 mitral, 21 tricuspid, nine
      pulmonary) was implanted in 1,047 consecutive patients (655 males, 392 females;
      mean age 62.1 +/- 12.4 years). Preoperatively, 75% of the patients were in NYHA
      class III or higher (mean 3.1). The most frequent comorbidities included atrial
      fibrillation (n = 381), coronary disease (n = 288) and diabetes (n = 172).
      RESULTS: The mean follow up was 78 months (range: 24-183 months); the total
      follow up was 6,887 patient-years (pt-yr) and was 99.8% complete. In-hospital
      mortality was 4% (n = 43; three valve-related). Survival (Kaplan-Meier) at five
      and 10 years was significantly better for aortic than for mitral valve patients
      (84% and 65% versus 75% and 41%, respectively) (Mantel-Cox, p < 0.001). A log
      rank analysis detected no statistical difference in the incidence of
      thromboembolism (p = 0.182) or bleeding (p = 0.375) between both groups. The
      overall linearized incidences were: thromboembolism 1.08%/pt-yr; bleeding
      0.91%/pt-yr; endocarditis 0.22%/pt-yr; paravalvular leakage 0.33%/pt-yr; and
      valve thrombosis 0.21%/pt-yr. Multivariate analysis (Cox regression) indicated
      age > 70 years (p < 0.0001), NYHA class > or = III (p < 0.0001), non-sinus rhythm
      (p = 0.001), concomitant CABG (p = 0.008) and higher INR values (p = 0.013) to be
      significant risk factors for death. CONCLUSION: This 15-year experience with the
      ATS bileaflet prosthesis showed excellent clinical outcomes for patients, with no
      structural failure and an acceptable incidence of adverse events.

PMID- 19852153
TI  - Coronary angiography prior to valve surgery: time to redefine the algorithms?

PMID- 19852152
TI  - Screening coronary angiography prior to surgery in rheumatic valvular heart
      disease: a study of 2,188 patients.
AB  - BACKGROUND AND AIM OF THE STUDY: The role of screening coronary angiography in
      Asian Indian patients with rheumatic heart disease (RHD) due to undergo valve
      replacement surgery is unclear. Hence, the study aim was to determine the
      prevalence of coronary artery disease (CAD), and to monitor its correlation with
      demographic variables and valvular lesion type, in this patient group. METHODS: A
      retrospective analysis of 2,188 consecutive patients (1,319 men, 869 women; mean
      age 48 +/- 7 years) with rheumatic valvular heart disease was conducted. The
      patients underwent preoperative coronary angiography in a tertiary care hospital
      between 1991 and 2004. RESULTS: The overall prevalence of CAD was 11% (12% in
      men, 8% in women). The prevalence of CAD in the age groups of 40-44, 45-49, 50
      54, 55-59 and > 60 years was 4%, 5%, 9%, 15% and 20% in men, and 2%, 2%, 3%, 7%
      and 10% in women, respectively. Both, age and male gender were independently
      associated with the occurrence of CAD (p < 0.01). The unadjusted odds ratio of
      having CAD was highest in patients with aortic stenosis (2.08; p < 0.01), and
      lowest in those with aortic regurgitation (AR) (0.58; p = 0.018). Those patients
      with AR also showed an independent inverse association with the occurrence of CAD
      (p = 0.006). CONCLUSION: The overall prevalence of CAD among Asian Indian
      patients with RHD was lower than that in patients from western countries. The cut
      off age to perform coronary angiographic screening should be maintained at 40
      years for men, and 55 years for women. The prevalence of CAD may be lower in
      those patients with AR.

PMID- 19852154
TI  - Heart abnormalities in Parkinson patients after discontinuation or continuation
      of ergot-derived dopamine agonists: a treatment-blinded echocardiographic study.
AB  - BACKGROUND AND AIM OF THE STUDY: Ergot-derived dopamine agonists (DAs) are used
      in the treatment of Parkinson's disease, but may be associated with valvular
      heart disease and pulmonary hypertension. The study aim was to examine changes in
      cardiovascular abnormalities after the discontinuation or continuation of anti
      parkinson treatment. METHODS: Parkinson patients treated with either ergot
      derived (n = 32) or non-ergot-derived (n = 8) DAs who had been diagnosed with
      valvular abnormalities or pulmonary hypertension, were included in this one-year
      follow up study. After an initial echocardiography, five patients continued ergot
      derived DA treatment, while the remaining 35 either changed (n = 27) or continued
      (n = 8) non-ergot-derived DA treatment. The patients were followed up after a
      mean of 14 months (range: 12-18 months). Changes in the severity of valve disease
      and pulmonary hypertension were evaluated by an analysis of digitally stored
      echocardiograms. The recordings were performed blinded to medical treatment,
      while the analyses were blinded to both the medical treatment and the timing of
      image acquisition. RESULTS: Follow up revealed the risk of worsening
      cardiovascular abnormalities to be 60% in patients who continued ergot-derived DA
      treatment, compared to 14% in those who changed to, or continued with, non-ergot
      derived DA medication (p < 0.05). Overall, patients who changed from ergot
      derived to non-ergot-derived DAs did not exhibit any significant worsening or
      improvement of their valve abnormality, although the pulmonary artery pressure
      (PAP) fell from 26 +/- 12 mmHg to 22 +/- 8 mmHg at follow up (p < 0.005).
      CONCLUSION: At one year after discontinuation of ergot-derived DAs, a mild but
      statistically significant reduction in PAP was detected. Overall, valvular
      regurgitation remained without definite worsening or improvement in these
      patients. Among patients who continued ergot-derived DAs despite a cardiovascular
      abnormality, the follow-up indicated an increased risk of worsening.

PMID- 19852155
TI  - An intra-left ventricular varicosity.

PMID- 19852156
TI  - Endocarditis of mitral annuloplasty ring due to coagulase-negative staphylococci.

PMID- 19852157
TI  - Aspergillus fumigatus mitral native valve endocarditis.

PMID- 19852158
TI  - Successful repair of a periannular tear complicated by aortic valve replacement
      using a Dacron patch.

PMID- 19852159
TI  - Polyvalvular disease associated with multiple congenital anomalies and
      pericentric inversion of chromosome 1 (p32q25).

PMID- 19852160
TI  - [More general practitioners are needed for clever quality registries].

PMID- 19852161
TI  - [New guidelines for more efficient treatment of hepatitis C. Individualized
      therapy increases the chance of cure].

PMID- 19852162
TI  - [Results following standardized routine at the emergency department. Fewer
      circulatory/respiratory arrest and increased survival with METTS].

PMID- 19852164
TI  - [Health and disease with focus on men].

PMID- 19852163
TI  - [Artificial neural networks make difficult medical decisions easier. Examples
      from pancreatology].

PMID- 19852165
TI  - [Male sexual dysfunction: not only a question of impotence].

PMID- 19852166
TI  - [The key role of testosterone in male hypogonadism].

PMID- 19852167
TI  - [The androgen receptor and effects of testosterone].

PMID- 19852168
TI  - [Erectile dysfunction--early sign of cardiovascular disease].

PMID- 19852169
TI  - [New knowledge about whiplash injuries].

PMID- 19852170
TI  - [What is a board decision worth?].

PMID- 19852171
TI  - [Non-systematic literature review on suicide prevention may mislead].

PMID- 19852172
TI  - [Premature infants' right to cae and the unwillingness to modify the view on
      abortions].

PMID- 19852173
TI  - MDT's five-minute interview.

PMID- 19852174
TI  - Different directions for the biological evaluation of biomaterials.
AB  - The standard tests for the biological evaluation of biomaterials, as promoted by
      the International Organisation for Standardisation, have evolved over the years
      to become an important part of the process for ensuring, as far as is possible,
      the biological safety of medical devices. There is, however, some scope for
      improvement, especially when we consider the extremely different requirements for
      new medical technology products.

PMID- 19852175
TI  - Leak testing medical devices.
AB  - Products and packaging require leak detection for quality assurance. This article
      compares and contrasts the two commonly used methods of pressure decay and trace
      gas testing and provides examples of using these techniques on a catheter and a
      sealed, impermeable pack.

PMID- 19852176
TI  - Stroke diagnosis with lab-on-a-chip.
AB  - A magnetic-based sensing platform with increased sensitivity has been developed
      for integration into lab-on-a-chip systems. The methodology consists of moving
      the magnetic particles to the most sensitive spot of the sensor. To demonstrate
      its effectiveness, the protein S100betabeta, a diagnostic marker for stroke, was
      used as target protein.

PMID- 19852177
TI  - Advanced materials: testing, QC and inspection.
AB  - The latest materials testing and analysis techniques are examined. Examples of
      their use illustrate how they can help in the development of new products, solve
      product and process issues and ensure quality control.

PMID- 19852178
TI  - New European guidance on borderline products.
AB  - The European Commission has recently updated an important guidance document on
      determining whether or not a medical product is subject to medical device or
      medicinal product regulations. In addition, a new manual that provides practical
      examples has also been issued. This article discusses these documents.

PMID- 19852179
TI  - Patient protection at risk in IEC 60601-1 3rd edition.
AB  - Engineers developing medical electrical equipment in accordance with IEC 60601-1
      3rd edition are in immediate need of short- and long-term solutions to avoid
      potentially hazardous designs as a result of misinterpretation of the
      requirements. Several options are described to ensure consistency and safety of
      devices.

PMID- 19852180
TI  - Micro abrasive blasting delivers 21st century stents.
AB  - As the applications for stents expand, contract manufacturers have responded with
      improvements in manufacturing operations.

PMID- 19852181
TI  - Implantable devices: challenges and opportunities.
AB  - Breakthroughs in technology are progressing at a phenomenal pace, but bringing
      them to the patient in the form of a device remains a challenge.The technical
      issues involved in designing an implantable device are outlined together with
      some potential solutions.

PMID- 19852182
TI  - Today's machine vision systems.
AB  - The latest machine vision technology is enabling manufacturers to increase
      production and offer complete quality control and traceability.

PMID- 19852183
TI  - Using simulation methods for orthopaedic implant design.
AB  - New virtual test methods are being used to better understand the functional
      performance of implants within the musculoskeletal system. Developing validated
      virtual models and tests reduces prototyping costs and compresses product
      development cycles.

PMID- 19852184
TI  - Alloy powders for medical applications.
AB  - The use of gas atomised alloy powders for the fabrication of medical devices
      offers a number of cost saving benefits and is therefore gaining in popularity.
      Their use in established and emerging manufacturing processes for products
      including hip and knee implants is described.

PMID- 19852185
TI  - Benefits of the spring.
AB  - The simple canted-coil spring may be the answer to manufacturers' device
      fastening difficulties.

PMID- 19852186
TI  - Murder by structure: dominance relations and the social structure of gang
      homicide.
AB  - Most sociological theories consider murder an outcome of the differential
      distribution of individual, neighborhood, or social characteristics. And while
      such studies explain variation in aggregate homicide rates, they do not explain
      the social order of murder, that is, who kills whom, when, where, and for what
      reason. This article argues that gang murder is best understood not by searching
      for its individual determinants but by examining the social networks of action
      and reaction that create it. In short, the social structure of gang murder is
      defined by the manner in which social networks are constructed and by people's
      placement in them. The author uses a network approach and incident-level homicide
      records to recreate and analyze the structure of gang murders in Chicago.
      Findings demonstrate that individual murders between gangs create an
      institutionalized network of group conflict, net of any individual's
      participation or motive. Within this network, murders spread through an epidemic
      like process of social contagion as gangs evaluate the highly visible actions of
      others in their local networks and negotiate dominance considerations that arise
      during violent incidents.

PMID- 19852187
TI  - How do people transform landscapes? A sociological perspective on suburban sprawl
      and tropical deforestation.
AB  - Humans transformed landscapes at an unprecedented scale and pace during the 20th
      century, creating sprawling urban areas in affluent countries and large-scale
      agricultural expanses in tropics. To date, attempts to explain these processes in
      other disciplines have had a disembodied, a historical quality to them. A
      sociological account of these changes emphasizes the role of strategic actions by
      states and coalitions of interested parties in transforming landscapes. It
      identifies the agents of change and the timing of transformative events. Case
      studies of suburban sprawl and tropical deforestation illustrate the value of the
      sociological approach and the wide range of situations to which it applies.

PMID- 19852188
TI  - Targeting capital: A cultural economy approach to understanding the efficacy of
      two anti-genetic engineering movements.
AB  - In the late 1990s, the British anti-genetic engineering (GE) movement effectively
      closed Britain's market for genetically modified foods, while the U.S. anti-GE
      movement had a negligible impact. In seeking to explain the different outcomes of
      these similar social movements, the authors draw upon the global commodity chains
      (GCC) literature to extend the understanding of the economic and industry-related
      openings and closures social movements face as they seek to promote social
      change. This analysis not only illustrates the importance of economic structures
      and organization for movement outcomes, but also shows how the economic sphere is
      culturally constituted. In this fashion, it broadens the social movement
      literature's understanding both of the way that political economy matters to
      movement efficacy and of the way that cultural processes infuse the economic
      sphere. The study advances the GCC literature by showing how GCCs are cultural as
      well as economic constructs.

PMID- 19852189
TI  - Oriental cockroaches.

PMID- 19852190
TI  - Smoking cessation toolbox for allergists.
AB  - OBJECTIVES: To review nicotine addiction, to examine how tobacco use has a direct
      negative impact on common disorders seen in allergy practice, and to provide a
      summary of the national guidelines for treating tobacco use and dependence. DATA
      SOURCES: OVID searches were performed cross-referencing the keywords tobacco
      cessation, tobacco use, environmental tobacco exposure, and smoking with multiple
      disorders commonly seen in allergy practice. References of the chosen articles
      were also examined. STUDY SELECTION: Articles were selected based on their
      relevance to the subject matter and currency. RESULTS: The current US smoking
      rate far exceeds the desired national goal established by Healthy People 2010.
      Efforts have been made by the US Public Health Department to streamline the
      treatment of smoking use and dependence for all physicians. Published research
      strongly supports the negative impact smoking has on asthma, chronic rhinitis,
      allergic sensitization, and immunodeficiency disorders. CONCLUSIONS: Allergists
      know the significant impact that smoking has and will make on the lives and
      health of patients. It is important for these specialists to make an impact on
      the chronic disease of tobacco addiction because it directly affects the care
      rendered. By using the standardized tobacco use treatment concept of the 5 A's
      (ask, advise, assess, assist, and arrange), allergists can make a positive impact
      on reducing US smoking rates and improve patient health. Screening, providing
      brief counseling, and prescribing first-line smoking cessation medications will
      help the United States get closer to achieving the national goal laid out in
      Healthy People 2010 of smoking rates of 12% or less.

PMID- 19852192
TI  - Sleep actigraphy evidence of improved sleep after treatment of allergic rhinitis.
AB  - BACKGROUND: Children with allergic rhinitis (AR) are reported to have disturbed
      sleep and daytime fatigue due to nasal obstruction. OBJECTIVE: To evaluate sleep
      impairment in children with AR using actigraphic evaluation. METHODS: Fourteen
      children aged 7 to 16 years with grass pollen-sensitized seasonal AR were
      enrolled. They completed the Total 4-Symptom Score (T4SS) scoring system for AR
      symptom score and the Pittsburgh Sleep Quality Index (PSQI) questionnaire for
      sleep quality, and they underwent actigraphy for 3 days in the pretreatment
      period. After topical corticosteroid and antihistaminic treatment for 8 weeks,
      actigraphy, the T4SS, and the PSQI were repeated. Fourteen healthy children aged
      8 to 16 years underwent actigraphy and completed the PSQI questionnaire as
      controls. RESULTS: There were no significant age or sex differences between the
      AR and control groups. Pretreatment PSQI and actigraphy scores were worse in the
      AR group vs the control group. After treatment, sleep quality improved, and there
      were no differences in actigraphy and PSQI scores between the 2 groups. Before
      treatment, the T4SS was significantly correlated with the sleep efficiency,
      daytime napping episodes, and total nap duration variables of actigraphy (r = 
      0.53, P = .004; r = 0.43, P = .02; and r = 0.39, P = .04, respectively). The T4SS
      was correlated with the total PSQI score (r = 0.67, P < .001). CONCLUSIONS: Sleep
      can be compromised in children with AR. There is a significant correlation of
      clinical symptom score with the actigraphic and PSQI variables. Therefore,
      actigraphy may be used as an objective tool to evaluate sleep disturbance in
      children with AR.

PMID- 19852191
TI  - The atopic march: what's the evidence?
AB  - OBJECTIVE: To review and compile data from published studies that provide support
      for the existence of the atopic march. DATA SOURCES: Relevant articles and
      references found via a PubMed search using the following keywords: atopic march,
      allergic march, atopic dermatitis, eczema, atopic eczema, atopy, rhinitis,
      wheeze, bronchiolitis, and asthma. STUDY SELECTION: All articles were reviewed
      and the most relevant were selected for inclusion in this review and for the
      compilation and graphical presentation of disease trends. RESULTS: Data on the
      prevalence of each phenotype of the atopic march confirm the temporal pattern of
      progression from eczema to allergic rhinitis and asthma. However, the atopic
      march as it is currently defined, is lacking precision, which affects its
      usefulness. Early events in the atopic march, such as eczema, may be more useful
      with more careful refinement of the phenotype into atopic and nonatopic eczema.
      CONCLUSION: Evidence supports that the atopic march is a useful paradigm to
      describe the clinically observed progression of atopy in certain children. There
      may be more precise phenotypes of the early stages of the atopic march that may
      improve its utility in predicting the development of later atopic, comorbid
      chronic disease.

PMID- 19852194
TI  - Differences in physicians' self-reported knowledge of, attitudes toward, and
      responses to the black box warning on long-acting beta-agonists.
AB  - BACKGROUND: Inhaled corticosteroids and long-acting beta-agonists (LABAs) are
      recommended for treating moderate to severe persistent asthma. The Food and Drug
      Administration has issued a black box warning (BBW) for LABAs. OBJECTIVE: To
      investigate physician knowledge of the BBW and its effect on the practice of
      specialists (pulmonologists and allergists) and primary care physicians (PCPs)
      (internists and family physicians). METHODS: A total of 1,107 physicians
      responded to a questionnaire to determine their awareness of the BBW and whether
      it changed their practice. RESULTS: The group comprised 429 pulmonologists
      (38.8%), 395 allergists (35.7%), 141 internists (12.7%), 132 family physicians
      (11.9%), and 10 pediatricians (0.9%). Comparing specialists with PCPs, there was
      approximately a 10% difference in the rate of knowledge concerning the BBW (99.0%
      vs 90.8%, P < .001). Approximately a quarter of specialists agreed with the BBW
      compared with 52.9% of family physicians and 40.3% of internists. Twice as many
      PCPs vs specialists agreed with the warning (45.6% vs 24.2%, P < .001). The PCPs
      were more likely to alter their prescribing habits than were specialists (40.1%
      vs 34.6%, P < .005). Specialists were more likely to discuss the warning with
      patients than were PCPs (87.4% vs 64.8%, P < .001). For mild persistent asthma,
      most respondents chose inhaled corticosteroids as the preferred first-line
      therapy, but 11.4% of PCPs and 2.1% of specialists identified LABA monotherapy as
      their first choice. For moderate to severe asthma, the pattern of response was
      similar. CONCLUSION: Although most physicians were aware of the BBW for LABAs,
      there was a difference in how specialists and PCPs approached it and altered
      their prescribing habits.

PMID- 19852193
TI  - Decrease in airway mucous gene expression caused by treatment with anti-tumor
      necrosis factor alpha in a murine model of allergic asthma.
AB  - BACKGROUND: Mucous hypersecretion increases asthma morbidity and mortality. Tumor
      necrosis factor a (TNF-a) levels are elevated in bronchoalveolar fluid, sputum,
      and monocyte membranes in some patients with asthma. Anti-TNF-a decreased asthma
      exacerbations and improved forced expiratory volume in 1 second in these
      patients. Whether anti-TNF-a reduces mucous cell metaplasia or hyperplasia has
      not been evaluated. OBJECTIVE: To investigate the role of anti-TNF-alpha in
      mucous hypersecretion. METHODS: BALB/c mice sensitized intraperitoneally and
      challenged intratracheally with ovalbumin were treated with 250 microg of anti
      TNF-alpha before ovalbumin sensitization and challenge or before only ovalbumin
      challenge. Control groups were sham treated. The tumor necrosis factor receptor
      (TNFR) mice (TNFR-/- and TNFR+/+) were identically sensitized and challenged.
      Seventy-two hours after the final challenge, the airway pressure time index
      (APTI), which measures airway hyperresponsiveness, was recorded. Mucous cell
      metaplasia was accessed by quantitative polymerase chain reaction for MUC-5AC
      (the epithelial cell mucous-inducing gene) and the percentage of periodic acid
      Schiff (PAS) staining of bronchial epithelial cells. A human airway cell line
      (constitutively expressing MUC-5AC) was pretreated with a NF-kappaB inhibitor
      before TNF-alpha culture. RESULTS: The mean (SE) fold change of MUC-5AC
      expression (compared with naive controls), the percentage of PAS-positive
      bronchiole epithelial cells, and the APTI decreased in BALB/c mice treated with
      anti-TNF-alpha before sensitization and challenge (4.9 [1.14], P = .007; 28.9%
      [6.8%], P < .001; and 545.8 [104.5] cm H2O/s, P < .001, respectively) and before
      challenge alone (9.3 [1.8], P = .03; 43.6% [10.7%], P = .009; and 896.8 [81.23]
      cm H2O/s, P = .06, respectively) compared with sham-treated mice (20.9 [3.9],
      82.4% [1.8%], and 1,055 [30.6] cm H20/s, respectively). MUC-5AC expression
      decreased in ovalbumin sensitized or challenged TNFR-/- (2.41 [0.4]) compared
      with ovalbumin sensitized or challenged TNFR+/+ mice (18.4 [2.5], P < .001). TNF
      alpha-induced MUC-5AC expression in human airway culture significantly decreased
      with pretreatment of a NF-kappaB inhibitor. CONCLUSIONS: Anti-TNF-alpha treatment
      reduces airway mucous cell metaplasia in a mouse model of asthma, which may in
      part underlie its beneficial effect as asthma therapy.

PMID- 19852195
TI  - Factors associated with severity and exacerbation of asthma: a baseline analysis
      of the cohort for reality and evolution of adult asthma in Korea (COREA).
AB  - BACKGROUND: Asthma presents with heterogeneous features, and patients show
      various phenotypes of differing severities. Therefore, it is necessary to define
      reliable predictable clinical factors that influence severity. To date, few large
      scale studies have gathered clinical data on adult asthma patients in Asia.
      OBJECTIVES: To establish an adult asthma cohort in Korea and to define
      significant factors associated with asthma severity and exacerbation. METHODS:
      Researchers from 11 university hospitals have established an asthma cohort termed
      the COhort for Reality and Evolution of adult Asthma in Korea (COREA). We
      classified the severity of asthma into 3 groups: mild, moderate, and severe. In
      this article, the first analysis of our cohort, we evaluate various clinical
      factors associated with the severity and exacerbation of asthma using data from
      1,260 asthma patients. RESULTS: Physician-evaluated severity of asthma was
      associated with a history of asthma exacerbation (P < .001), a history of smoking
      (P < .001), symptom duration (P = .007), and treatment duration (P < .001). It
      was also significantly correlated with predicted forced vital capacity (FVC) and
      forced expiratory volume in 1 second (FEV1) values and FEV1/FVC ratio (all P <
      .001). Previous exacerbation was associated with smoking (P = .02), predicted FVC
      and FEV1 values (both P < .001), FEV1/FVC ratio (P = .02), airway
      hyperresponsiveness (P = .002), and duration of disease (P < .001). CONCLUSIONS:
      Previous exacerbation, duration of disease, and decrease in lung function were
      important clinical indices associated with asthma severity in the COREA study
      patients. Our long-term follow-up study is expected to soon yield more accurate
      and detailed outcomes.

PMID- 19852196
TI  - Factors associated with delayed use or nonuse of systemic corticosteroids in
      emergency department patients with acute asthma.
AB  - BACKGROUND: Little is known about factors associated with systemic corticosteroid
      (SC) use in emergency department (ED) patients with acute asthma. OBJECTIVE: To
      determine the patient and system factors associated with delayed use or nonuse of
      SCs in the ED. METHODS: We analyzed the asthma component of the National
      Emergency Department Safety Study. Patients with acute asthma in 62 urban EDs in
      23 US states between 2003 and 2006 were identified. The primary outcome measure
      was the pattern of SC use in the ED, which was categorized as timely use (< or =
      60 minutes), delayed use (> 60 minutes), or nonuse. Multinomial logistic
      regression was performed to identify factors associated with delayed use or
      nonuse of SCs. RESULTS: A total of 2,559 of 3,798 patients with acute asthma
      (67.4%) received SCs. Of these, the median door-to-SC time was 62 minutes
      (interquartile range, 35-100 minutes), with 1,319 patients (51.5%) having delayed
      SC treatment. Nonuse of SCs was largely explained by markers of asthma
      exacerbations (never intubated for asthma, lower respiratory rate, and higher
      oxygen saturation). In contrast, in addition to these factors, delayed SC
      treatment was associated with age of 40 years or older, female sex, longer
      duration of symptoms, ED presentation between 8 AM and 11:59 PM, and ED with a
      longer average patient wait time. CONCLUSIONS: Physicians in the ED seem to
      appropriately administer SCs to higher-acuity asthmatic patients; however, the
      additional nonmedical factors represent opportunities to improve the timeliness
      of SC treatment in the ED.

PMID- 19852197
TI  - Assessing the validity of self-reported medication adherence among inner-city
      asthmatic adults: the Medication Adherence Report Scale for Asthma.
AB  - BACKGROUND: A validated tool to assess adherence with inhaled corticosteroids
      (ICS) could help physicians and researchers determine whether poor asthma control
      is due to poor adherence or severe intrinsic asthma. OBJECTIVE: To assess the
      performance of the Medication Adherence Report Scale for Asthma (MARS-A), a 10
      item, self-reported measure of adherence with ICS. METHODS: We interviewed 318
      asthmatic adults receiving care at 2 inner-city clinics. Self-reported adherence
      with ICS was measured by MARS-A at baseline and 1 and 3 months. ICS adherence was
      measured electronically in 53 patients. Electronic adherence was the percentage
      of days patients used ICS. Patients with a mean MARS-A score of 4.5 or higher or
      with electronic adherence of more than 70% were defined as good adherers. We
      assessed internal validity (Cronbach alpha, test-retest correlations), criterion
      validity (associations between self-reported adherence and electronic adherence),
      and construct validity (correlating self-reported adherence with ICS beliefs).
      RESULTS: The mean patient age was 47 years; 40% of patients were Hispanic, 40%
      were black, and 18% were white; 53% had prior asthma hospitalizations; and 70%
      had prior oral steroid use. Electronic substudy patients were similar to the rest
      of the cohort in age, sex, race, and asthma severity. MARS-A had good interitem
      correlation in English and Spanish (Cronbach alpha = 0.85 and 0.86, respectively)
      and good test-retest reliability (r = 0.65, P < .001). According to electronic
      measurements, patients used ICS 52% of days. Continuous MARS-A scores correlated
      with continuous electronic adherence (r = 0.42, P<.001), and dichotomized high
      self-reported adherence predicted high electronic adherence (odds ratio, 10.6;
      95% confidence interval, 2.5-44.5; P < .001). Construct validity was good, with
      self-reported adherence higher in those saying daily ICS use was important and
      ICS were controller medications (P = .04). CONCLUSIONS: MARS-A demonstrated good
      psychometric performance as a self-reported measure of adherence with ICS among
      English- and Spanish-speaking, low-income, minority patients with asthma.

PMID- 19852198
TI  - High sensitization rate to food allergens in breastfed infants with atopic
      dermatitis.
AB  - BACKGROUND: The differences in the characteristics of breastfed and formula fed
      individuals with allergy have been addressed in few studies and remain
      controversial. OBJECTIVE: To evaluate the effect of breastfed on the development
      of food allergy and sensitization against food allergens in infants with atopic
      dermatitis (AD). METHODS: We reviewed 143 infants (77 boys and 66 girls) with AD
      who were younger than 6 months and were classified into the following 3 groups
      based on the type of feeding they received: breastfed, mixed feeding, and formula
      fed. All infants had never been fed egg or soy. The total and specific IgE levels
      were then assessed using a commercially available assay. RESULTS: The total IgE
      level (P = .004) and egg specific IgE level (P = .002) were significantly higher
      in the BF group than in the FF group. The rate of sensitization to egg (P = .001)
      was also significantly higher in the BF group when compared with the FF group, as
      was the egg allergy rate (P = .004). CONCLUSION: Our results suggest that
      breastfeeding might not always be beneficial in allergy prevention in some high
      risk infants.

PMID- 19852199
TI  - Influence of dose and frequency of antigen injection on IgE development in young
      children: a comparison of fire ant stings and tetanus immunizations.
AB  - BACKGROUND: Previous studies suggest that small antigen doses given frequently
      are more likely to induce IgE production than are large antigen doses given
      infrequently. OBJECTIVE: To compare the prevalence of antitetanus IgE resulting
      from the relatively large dose of tetanus toxoid delivered by standard
      immunizations at 2, 4, 6, and 18 months of age with the previously reported
      prevalence of anti-fire ant venom IgE resulting from the relatively small dose of
      venom delivered sporadically by accidental fire ant stings in children younger
      than 5 years. METHODS: This study uses previously published data on the
      prevalence of IgE antibodies to imported fire ant venom among children living in
      an imported fire ant endemic area of Georgia and antitetanus IgE measurements of
      children recruited between August 1, 2003, and December 30, 2007, as part of the
      Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study in
      Michigan, where there are no imported fire ants. The prevalence of anti-fire ant
      venom IgE antibodies was compared with the prevalence of antitetanus IgE
      antibodies in these 2 cohorts of children. RESULTS: The reported prevalence of
      IgE to fire ant venom among 42 children 2 to 5 years old was 57.1% using a cutoff
      of 0.1 IU/mL and 35.7% using a cutoff of 0.35 IU/mL. The prevalence of
      antitetanus IgE in 395 children 2 years old was 52.9% using a cutoff of 0.1 IU/mL
      and 42.7% using a cutoff of 0.35 IU/mL. The proportion of children with
      detectable anti-fire ant venom IgE was not statistically significantly different
      from the proportion of those with antitetanus IgE at either cutoff level (P = .74
      and .50 at 0.1 and 0.35 IU/mL, respectively). CONCLUSIONS: The relatively large
      dose of tetanus toxoid delivered 4 times during the first 24 months of life
      produces detectable tetanus specific IgE antibodies as frequently as the smaller
      doses of venom delivered sporadically by fire ant stings in young children.

PMID- 19852201
TI  - Bromotyrosines in sputum proteins and treatment effects of terbutaline and
      budesonide in asthma.
AB  - BACKGROUND: Inhaled corticosteroids are widely used in the treatment of
      persistent asthma, usually combined with inhaled beta2-agonists. Previous
      research suggests that short-acting beta2-agonists (SABAs) may downregulate the
      anti-inflammatory effects of inhaled corticosteroids, thereby increasing asthma
      morbidity. OBJECTIVE: To determine whether 3-bromotyrosine and 3,5
      dibromotyrosine levels, specific markers of eosinophil activation, reflect
      treatment effects on airway inflammation of inhaled corticosteroids and SABAs and
      support previous conclusions. METHODS: Levels of 3-bromotyrosine and 3,5
      dibromotyrosine were measured in sputum supernatants using stable isotope
      dilution gas chromatography-mass spectrometry in a randomized, placebo
      controlled, crossover study of treatment with terbutaline, budesonide, and their
      combination in patients with persistent asthma. Thirty-four individuals were
      randomized, and 28 completed the study. RESULTS: Treatment with budesonide
      lowered median 3-bromotyrosine levels compared with treatment with placebo,
      terbutaline, and budesonide-terbutaline (0.24 vs 0.64, 0.62, and 0.43 3
      bromotyosine/tyrosine [mmol/mol]; P < .05) and lowered median 3,5-dibromotyrosine
      levels compared with placebo and terbutaline treatments (0.04 vs 0.11 and 0.07
      3,5-dibromotyrosine/ tyrosine [mmol/mol], P < .05). Unlike eosinophil numbers, 3
      bromotyrosine and 3,5-dibromotyrosine levels did not increase with terbutaline
      treatment compared with placebo treatment but were significantly raised when
      terbutaline was added to budesonide treatment. 3-Bromotyrosine levels correlated
      significantly with eosinophil cationic protein levels in all groups. CONCLUSIONS:
      3-Bromotyrosine and 3,5-dibromotyrosine levels reflect treatment effects in
      asthma and support previous findings that SABAs impair the anti-inflammatory
      effects of inhaled corticosteroids. In addition to eosinophil numbers and
      eosinophil cationic protein levels, these modified tyrosine residues provide
      useful information about the inflammatory state of the airways.

PMID- 19852200
TI  - Differences in total and allergen specific IgE during pregnancy compared with 1
      month and 1 year post partum.
AB  - BACKGROUND: Pregnancy alters the function of many body systems, including the
      immune system. However, little is known regarding the effect of pregnancy on
      maternal IgE levels or atopy. OBJECTIVE: To determine whether pregnancy
      consistently influences serum levels of total or allergen specific IgE. METHODS:
      Blood samples were obtained from 764 women during the third trimester of
      pregnancy and 1 month post partum. A third sample was obtained from 106 of these
      women 1 year post partum. Samples were analyzed for total and specific IgE to 8
      regionally common allergens using a commercially available system. Sensitization
      was defined as an allergen specific IgE level of 0.35 kU of allergen per liter or
      higher to any allergen. RESULTS: Total IgE increased significantly post partum,
      both at 1 month (40.36 vs 35.37 IU/mL intrapartum; P = .001) and at 1 year (44.97
      vs 37.00 IU/mL intrapartum; P = .005). Allergen specific IgE decreased
      significantly at 1 month for cat, dog, ragweed, timothy grass, and egg (P = .001
      to P = .02) but not for dust mite, cockroach, or Alternaria (P = .15 to P = .90).
      Similar patterns of change in total and specific IgE were seen at 1 year.
      However, on average, only 3.5% of participants changed sensitization status to
      the individual allergens studied during the 1 year of observation. CONCLUSIONS:
      Compared with intrapartum levels, total IgE levels increased significantly at 1
      month and 1 year post partum. Conversely, at the same time points, IgE levels
      specific for common allergens significantly declined to most but not all
      allergens. Few women changed their sensitization status over 1 year.

PMID- 19852202
TI  - Latex as a significant source of Hevea brasiliensis allergen exposure.

PMID- 19852203
TI  - Unusual complication with use of an instant cold pack.

PMID- 19852204
TI  - Regulation of monocyte chemoattractant protein 1 by cysteinyl leukotriene D4 in
      human lung epithelial A549 cells.

PMID- 19852205
TI  - Severe anaphylactoid shock secondary to gadolinium contrast media.

PMID- 19852206
TI  - [In vitro studies of the mechanical load capability of resorbable monofilament
      suture materials].
AB  - In a vast spectrum of wound closures there is an indication for resorbable suture
      materials. For surgeons detailed knowledge of the physicochemical properties is
      important in order to find the right suture for each indication. For this
      purpose, various new monofilament polymers were employed. The objective of the
      present study was to investigate the effects of hydrolysis and gamma-irradiation
      on the linear strength. The final analysis of all tested suture materials
      concluded that gamma-irradiation had no effects on linear strength. However, the
      analysis showed significant discrepancies between individual polymers with regard
      to loss of tensile strength associated with hydrolysis. Polydioxanone- and
      caprolactone-lactid-based resorbable suture materials both displayed adequate
      tensile strength after a five-week period of hydrolysis. In comparison the
      triblock-copolymer is subject to rapid degradation. Polydioxanone- and
      caprolactone-lactid-based resorbable suture materials are indicated for use in
      tissues which require mechanical support over a longer period. Monosyn is more
      suitable for short-term wound support.

PMID- 19852207
TI  - [Eosinophilic granuloma of the mandible--a case report].
AB  - BACKGROUND: Langerhans cell histiocytosis is characterized by a clonal
      proliferation of Langerhans cells. The clinical manifestation varies from a
      localized lesion (eosinophilic granuloma) to a systemic disease. The diagnosis
      can only be confirmed histopathologically. A comprehensive staging is necessary
      to determine the extent of the disease and to establish an adequate therapy. CASE
      REPORT: We report on a 27 years old patient who was referred to our clinic with
      the diagnosis of an osteomyelitis of the mandibular angle and a pathological
      fracture after extraction of tooth 38 one month before. Curettage and primary
      bone grafting were performed. In the histological examination of the specimen
      infiltrates of a Langerhans cell histiocytosis were found. The clinical and
      radiological staging demonstrated a solitary mandibular lesion (eosinophilic
      granuloma). After wound healing a low-dose radiotherapy with 6 Gray was
      performed. Two years after completion of the therapy the patient is asymptomatic
      and does not show any evidence of recurrence. CONCLUSION: Langerhans cell
      histiocytosis has to be included in the differential diagnosis of osteolytic
      lesions of the mandible. A low-dose radiotherapy is a reasonable and well
      tolerated treatment option.

PMID- 19852208
TI  - [Locator or ball attachment: a guide for clinical decision making].
AB  - Various attachments are available to retain overdentures on natural roots or
      implants. Technical aspects, the clinical handling, the capability to adapt or
      repair and the costs are parameters to be considered when choosing the
      appropriate attachment. Ball attachments and bars are clinically established and
      well documented. Ball attachments as prefabricated, unsplinted units are easily
      replaceable and show hygienic advantages, while bars show favorable stability.
      The Locator is a newer, popular clinical alternative to these established
      attachments. The ball attachment and the Locator are compared from a technical
      and clinical point of view.

PMID- 19852209
TI  - President's message, AMCA president 2008.

PMID- 19852210
TI  - 2009 AMCA Memorial Lecture Honoree: Dr. Chester Lamar Meek.
AB  - Chester Lamar Meek (1944-2000), 2009 AMCA Memorial Lecture Honoree, was husband
      to Sharon Kay Meek, father of Bradley Lamar and Jody Keith, and a member of the
      faculty of Louisiana State University for 25 years when he passed away on June
      27, 2000, while conducting field research on mosquitoes in Cleveland,
      Mississippi. Dr. Meek was born in Monticello, Arkansas, and attended Ouachita
      Baptist University, University of Arkansas, and Texas A&M University, where he
      took his B.S., M.S., and Ph.D., respectively. He was an expert in the biology and
      control of rice-field mosquitoes and in forensic entomology. He served in the
      medical service corps of the US Army, authored or co-authored over 65 scientific
      publications, and was mentor to graduate students in medical and forensic
      entomology. Dr. Meek was a member of the Louisiana Mosquito Control Association,
      the Texas Mosquito Control Association, the American Mosquito Control
      Association, the Entomological Society of America, the American Registry of
      Professional Entomologists, and the Society for Vector Ecology. He received the
      American Mosquito Control Association's awards for Meritorious Service (1986) and
      the Memorial Lectureship Award (1991) and was recognized for his service by the
      Louisiana Mosquito Control Association with the 1989 Hathaway-Ritter
      Distinguished Achievement award.

PMID- 19852211
TI  - The mosquitoes of Glacier National Park, Montana.
AB  - Twenty-nine mosquito species belonging to 4 genera are reported for Glacier
      National Park, Montana. These include 22 originally reported by H.G. Dyar and 7
      additional records, one of which, Ochlerotatus euedes (=Aedes eueedes) is a new
      state record for Montana.

PMID- 19852212
TI  - Description of the pupa of the Himalayan mosquito, Ochlerotatus pulchriventer.
AB  - The pupa of Ochlerotatus pulchriventer (=Aedes pulchriventer) is described and
      illustrated for the first time. It was collected at midrange altitudes in the
      Himalaya Mountains of Nepal. A subspecies from Taiwan is discussed.

PMID- 19852213
TI  - Introduction, control, and spread of Aedes albopictus on Grand Cayman Island,
      1997-2001.
AB  - Infestations of Aedes albopictus were first identified in the Cayman Islands on
      June 19, 1997. Control techniques that had previously been effective in the
      elimination of Ae. aegypti from these islands were employed with the aim of
      eliminating this species. Chemical control methods against adult mosquitoes used
      a combination of ultra-low-volume applications of fenthion, backpack spraying
      with permethrin, and residual wall treatments with lambda-cyhalothrin. Larval
      stages were also targeted with the use of granular formulations of temephos and
      methoprene applied to all containers capable of sustaining larval development.
      For a 2-year period after the discovery of the introduction the abundance of this
      mosquito remained low (Breteau index = 0.6); however, in 1999 Ae. albopictus
      became firmly established (Breteau index = 5.5). By the end of 2001 it was
      apparent that the control methods utilized had failed to stop the spread of this
      species. This work describes the control methods utilized and discusses possible
      reasons for the failure of the elimination campaign.

PMID- 19852214
TI  - Reintroduction of Aedes aegypti into Grand Cayman.
AB  - In October 2002 Aedes aegypti was detected on Grand Cayman after an absence of 5
      years. This study outlines the techniques used by the Mosquito Research & Control
      Unit of the Cayman Islands to monitor the reintroduction of Ae. aegypti and to
      determine the extent of the new infestation. Suggestions are made for
      improvements of port disinsection activities to minimize further introductions.

PMID- 19852215
TI  - Rapid assessment of mosquitoes and arbovirus activity after floods in
      southeastern Kansas, 2007.
AB  - A rapid assessment was conducted in July-August 2007 to determine the impact of
      heavy rains and early summer floods on the mosquitoes and arbovirus activity in 4
      southeastern Kansas counties. During 10 days and nights of collections using
      different types and styles of mosquito traps, a total of 10,512 adult female
      mosquitoes representing 29 species were collected, including a new species record
      for Kansas (Psorophora mathesoni). High numbers of Aedes albopictus were
      collected. Over 4,000 specimens of 4 Culex species in 235 species-specific pools
      were tested for the presence of West Nile, St. Louis, and western equine
      encephalitis viruses. Thirty pools representing 3 Culex species were positive for
      West Nile virus (WNV). No other arboviruses were detected in the samples.
      Infection rates of WNV in Culex pipiens complex in 2 counties (10.7/1,000 to
      22.6/1,000) and in Culex salinarius in 1 county (6.0/1,000) were sufficiently
      high to increase the risk of transmission to humans. The infection rate of WNV in
      Culex erraticus was 1.9/1,000 in one county. Two focal hot spots of intense WNV
      transmission were identified in Montgomery and Wilson counties, where infection
      rates in Cx. pipiens complex were 26/ 1,000 and 19.9/1,000, respectively. Despite
      confirmed evidence of WNV activity in the area, there was no increase in human
      cases of arboviral disease documented in the 4 counties for the remainder of
      2007.

PMID- 19852216
TI  - Arboviruses isolated from mosquitoes collected from urban and peri-urban areas of
      eastern Australia.
AB  - To determine the presence of arboviruses in mosquito populations from major urban
      areas of eastern Australia, a total of 67,825 mosquitoes, representing -60
      species, was collected and tested from Cairns, Brisbane, and Sydney between
      January 2005 and April 2008. Mosquito pools were screened by inoculation onto
      mosquito cell cultures and the detection of viral antigen using a panel of
      flavivirus and alphavirus monoclonal antibodies in an enzyme-linked immunosorbent
      assay. Suspect positive samples were confirmed using virus-specific real-time
      reverse transcriptase-polymerase chain reaction assays. No flaviviruses were
      detected, but 2 alphaviruses were isolated from mosquito pools collected from
      Cairns, with 1 Barmah Forest virus isolate from a pool of 100 Aedes vigilax and 1
      Ross River virus isolate from a pool of 83 Verrallina carmenti. In addition, a
      single Aedes alternans collected from Sydney yielded an isolate most similar to
      Stretch Lagoon virus, a newly described virus from the genus Orbivirus. These
      results suggest that during the study, arboviruses were circulating at a low
      level in the areas sampled. The findings from this study will promote public
      health awareness of the risk of arboviruses in urban areas, leading to more
      informative public health campaigns to safeguard the Australian public.

PMID- 19852217
TI  - Ecological study of avian malaria vectors on the island of Minami-Daito, Japan.
AB  - The seasonal prevalence and spatial distribution of mosquitoes were examined as
      part of an avian malaria study on the oceanic island of Minami-Daito Island,
      Japan. Because dry ice was not available in this study, yeast-generated CO2 was
      used to attract biting mosquitoes. Adult mosquitoes were collected biweekly using
      battery-operated traps enhanced with yeast-generated CO2 and a gravid trap from
      March 2006 to February 2007. The CO2-baited traps were distributed in 4 different
      habitats: sugar cane field, forest and vegetation ring, residential area, and
      swamp area. At 3 collection sites beside sugar cane fields, traps were fixed at 2
      different heights (3 and 6 m above the ground). A total of 1,437 mosquitoes of
      the following 9 species were collected: Culex quinquefasciatus, Aedes albopictus,
      Coquillettidia sp., Mansonia uniformis, Culex rubithoracis, Armigeres subalbatus,
      Lutzia fuscanus, Aedes daitensis, and Aedes togoi. Among them, Cx.
      quinquefasciatus, Ae. albopictus, and Coquillettidia sp. were dominant. The high
      density and wide distribution of Cx. quinquefasciatus throughout the island
      suggested the importance of this species as a principal vector of avian malaria
      on the island.

PMID- 19852218
TI  - Response of adult mosquitoes to light-emitting diodes placed in resting boxes and
      in the field.
AB  - The response of adult mosquitoes to 4 light-emitting diode (LED) wavelengths was
      evaluated using diode-equipped sticky cards (DESCs) and diode-equipped resting
      boxes at 2 sites in north central Florida. Wavelengths evaluated were blue (470
      nm), green (502 nm), red (660 nm), and infrared (IR) (860 nm). When trapping with
      DESCs, 15 mosquito species from 7 genera (Aedes, Anopheles, Coquillettidia,
      Culex, Mansonia, Psorophora, and Uranotaenia) were captured. Overall,
      approximately 43.8% of all mosquitoes were trapped on DESCs fitted with green
      LEDs. Significantly more females of Aedes infirmatus, Aedes vexans, and Culex
      nigripalpus were captured on DESCs fitted with blue LEDs compared with red or IR
      LEDs. DESCs with blue LEDs captured significantly more Culex erraticus females
      than those with IR LEDs. Using resting boxes, 12 species from 5 genera
      (Anopheles, Coquillettidia, Culex, Mansonia, and Uranotaenia) were collected.
      Resting boxes without LEDs captured 1,585 mosquitoes (22.2% of total). The fewest
      number of mosquitoes (16.7%) were collected from boxes affixed with the blue
      LEDs. Significantly more Anopheles quadrimaculatus females were aspirated from
      resting boxes fitted with red and IR LEDs than from those with blue or green
      LEDs, or from the unlit control. Blood-fed mosquitoes were recovered in highest
      numbers from unlit resting boxes, followed by resting boxes fitted with green,
      IR, and blue LEDs. Culex erraticus accounted for the majority of blood-fed
      mosquitoes followed by Coquillettidia perturbans. No blood-fed mosquitoes were
      recovered from resting boxes fitted with red LEDs.

PMID- 19852219
TI  - Are commercially available essential oils from Australian native plants repellent
      to mosquitoes?
AB  - While the use of topical insect repellents, particularly those containing
      synthetic active ingredients such as deet (N,N-diethyl-3-methylbenzamide), are a
      mainstay in personal protection strategies emphasized in public health messages,
      there is a growing demand in the community for alternative repellents,
      particularly those of botanical origin and thus deemed to be "natural." This
      study evaluated the repellency of essential oils from 11 Australian native plants
      in 5% v/v formulations against Aedes aegypti, Culex quinquefasciatus, and Culex
      annulirostris under laboratory conditions. A blend of the top 3 performing oils
      was then compared with deet and a commercially available botanical insect
      repellent. All essential oils provided at least some protection against the 3
      mosquito species, with the longest protection time (110 min) afforded by
      Prostanthera melissifolia against Cx. quinquefasciatus. Mean protection times
      against Ae. aegypti were substantially lower than those for the Culex spp.
      tested. Deet provided significantly longer protection against Ae. aegypti than
      both the 5% v/v blend of Leptospermum petersonii, Prostanthera melissifolia, and
      Melaleuca alternifolia (the 3 most effective oils) and the commercial botanical
      repellent. The results of this study indicate that these essential oils from
      Australian native plants offer limited protection against biting mosquitoes and
      that a blend of essential oils holds may offer commercial potential as a short
      period repellent or under conditions of low mosquito abundance. However, it is
      important that public health messages continue to emphasize the greater
      effectiveness of deet-based repellents in areas with risks of mosquito-borne
      disease.

PMID- 19852220
TI  - Investigation of fathead minnows (Pimephales promelas) as a biological control
      agent of Culex mosquitoes under laboratory and field conditions.
AB  - Many urban areas have engineered storm-water runoff control structures such as
      ditches and detention ponds. These often serve as excellent habitats for Culex
      pipiens and Culex restuans, the primary enzootic vectors of West Nile virus in
      the Midwest. We evaluated predation and control of these species by a fish
      species native to Wisconsin, the fathead minnow (Pimephales promelas). In the
      lab, a single minnow consumed an average of 74 Cx. pipiens larvae in a 24-h
      period. Minnow gender and age had minimal effect on predation of 2nd and 4th
      instars. In the field, fathead minnows (1,000 fish/ha) were introduced 1 time
      into 3 storm-water ditches with an additional 9 sites serving as controls. Sites
      where fish were introduced required no Bacillus sphaericus (VectoLex) treatments
      during the 10-week experiment. The control sites required 19 VectoLex treatments
      during the same 10-week time span. Survival analysis revealed a statistically
      significant difference in time to first VectoLex treatment between fish sites and
      control sites. Our results suggest fathead minnows may provide a long-lasting and
      ecologically and economically feasible alternative to the use of VectoLex for
      Culex larval control.

PMID- 19852221
TI  - Evaluation of Bacillus sphaericus against Mansonia dyari larvae in phosphate
      lakes in Polk County, Florida.
AB  - Effective Mansonia larval control is difficult to achieve in Polk County,
      Florida, because the larvae attach to the root and stem mass of water lettuce
      (Pistia stratiotes) and water hyacinth (Eichhornia crassipes). This study
      evaluated 2 Bacillus sphaericus larvicides as possible control products in 3
      phosphate lakes in 2 areas maintained by Polk County Mosquito Control. VectoLex
      WDG was applied at 56 kg/km2 and 170 kg/km2 and VectoLex CG at 560 kg/km2 and
      1,100 kg/km2. One lake in each site was an untreated control. Larval collections
      were made by collecting water lettuce plants that were shaken, washed, and
      processed through a series of sieves to grade larvae as early (1st, 2nd) and late
      (3rd, 4th) instars. Pretreatment and posttreatment collections were made in each
      lake. More than 3,100 larvae were collected during the study. Approximately 65%
      of the larvae collected were Ist/2nd instars in both areas. The higher rate of
      VectoLex CG reduced the larval population 63% and the higher rate of VectoLex WDG
      by 44%. Against the Ist/2nd instar aggregate the higher rate of VectoLex CG was
      more effective (69%) than the VectoLex WDG. The VectoLex CG granules appeared to
      remain nearer the surface and the larvae than the WDG granules. Better
      effectiveness might have been attained if the entire lake had been treated. In
      this study, VectoLex CG appeared to be more effective than VectoLex WDG.

PMID- 19852222
TI  - Efficacy of novaluron against Culex quinquefasciatus in small- and medium-scale
      trials, India.
AB  - Novaluron 10% emulsifiable concentrate (EC), an insect growth regulator (IGR),
      was tested against Culex quinquefasciatus immatures at 1, 5, and 10 mg active
      ingredient (AI)/m2 applied to cesspits, drains, and abandoned wells. The IGR
      produced 80-100% inhibition of adult emergence (IE) for > 1 week (10-14 days) in
      cesspits, 1-2 weeks in street drains, and 5-10 weeks in abandoned wells at the 3
      application rates. The efficacy increased with the increasing dose in street
      drains and abandoned wells. The residual activity of the IGR was longer in
      abandoned wells compared to drains and cesspits. Based on the small-scale trial,
      doses of 1, 5, and 10 mg AI/m2 were used in the medium-scale trial for cesspits,
      abandoned wells, and street drains, respectively. The efficacy observed in medium
      scale trial was similar to that in the small-scale trial. The results indicate
      that novaluron 10% EC can be used for larval control against Cx. quinquefisciatus
      at the application rate of 1 mg AI/m2 at 10-day intervals in cesspits, at 5 mg
      AI/m2 at 2-month intervals in abandoned wells, and at 10 mg AI/m2 applied at
      fortnightly intervals to drains. Even at the lowest rate of 1 mg AI/m2, the IGR
      prevented adult emergence for at least a week in cesspits and street drains and
      for a month in abandoned wells. Novaluron 10% EC could be one of the options for
      larval control operations in integrated vector management.

PMID- 19852223
TI  - Canopy penetration and deposition of barrier sprays from electrostatic and
      conventional sprayers.
AB  - An experimental study was conducted to investigate the usefulness of
      electrostatic and conventional sprayers for barrier applications. Two
      conventional and three electrostatic sprayers were used in the study. Usefulness
      of the sprayers was rated based on penetration of spray into and deposition onto
      2 sides of leaves on natural vegetation. Bifenthrin (Talstar adulticide) was
      applied at labeled rate, fluorescent dye was added to the tank mix as tracer, and
      all sprayers applied the dye and insecticide at the same rate. The results
      indicated that sprayers producing larger droplets produced significantly higher
      deposition on vegetation in barrier applications than the sprayers producing
      smaller droplets. Sprayers with higher air velocity at the nozzle discharge
      proved significantly better for barrier sprays than the sprayers with lower air
      velocity. Electrostatic sprayers did not show any improvement in deposition on
      vegetation or in penetration into vegetation over the conventional sprayers.
      There was no difference in deposition between truck-mounted and backpack
      sprayers.

PMID- 19852224
TI  - Spray characterization of ultra-low-volume sprayers typically used in vector
      control.
AB  - Numerous spray machines are used to apply pesticides for the control of human
      disease vectors, such as mosquitoes and flies, and the selection and setup of
      these machines significantly affects the level of control achieved during an
      application. The droplet spectra produced by 9 different ultra-low-volume
      sprayers with oil- and water-based spray solutions were evaluated along with 2
      thermal foggers with the use of diesel-based spray solutions. The droplet spectra
      from the sprayers were measured with the use of laser diffraction droplet sizing
      equipment. The volume median diameter from the sprayers ranged from 14.8 to 61.9
      microm for the oil-based spray solutions and 15.5 to 87.5 microm for the water
      based spray solutions. The 2 thermal foggers generated sprays with a volume
      median diameter of 3.5 microm. The data presented will allow spray applicators to
      select the spray solution and sprayer that generate the droplet-size spectra that
      meet the desired specific spray application scenarios.

PMID- 19852225
TI  - Environmental factors affecting efficacy of bifenthrin-treated vegetation for
      mosquito control.
AB  - The use of pesticide-treated vegetation as a barrier for control of nuisance and
      disease-bearing mosquitoes has become an option for mosquito management for home
      owners and public health and mosquito control professionals. Potted wax myrtle
      and azalea plants were treated with bifenthrin (0.79% AI) at maximum label rate
      using backpack and electrostatic sprayers and exposed to various treatments that
      could affect the residual degradation of the applied pesticides. Treatments
      included leaf aspect, simulated rainfall, shade, and natural sun exposure with
      the residual effectiveness of leaves examined in tarsal contact Petri dish assays
      using laboratory-reared Aedes aegypti. There was no significant difference in
      efficacy between the adaxial (top) or abaxial (bottom) surfaces of
      electrostatically or backpack-treated leaves. Significant differences existed
      between application method, plant species, and exposure with most significant
      effects between weeks 1 and 4. Simulated heavy rainfalls applied 3 times weekly
      reduced knockdown by leaves treated with electrostatic and backpack methods with
      reductions seen as soon as 1 wk after treatment. Reductions were seen with both
      wax myrtle and azalea leaves and after 1, 4, and 24 h contact of mosquitoes to
      leaves. Placement of plants with full exposure to sunlight also significantly
      reduced efficacy compared to plants placed in the shade. Differences were
      observed most often for 4 and 24 h knockdown counts, and significant decreases
      were seen from week 4 onwards. Clearly factors such as rain and exposure to sun
      impact degradation of efficacy of bifenthrin-treated vegetation in the field.
      Degradation of bifenthrin efficacy was slowest in sites protected from rain and
      sun, which coincide with preferred resting site locations for many mosquito
      species.

PMID- 19852226
TI  - Effect of effluent-treated water on mosquito development in simulated ponds at
      the Prado Wetlands of southern California.
AB  - Studies were conducted to determine the effect of water quality on mosquito
      development at the Prado Wetlands in southern California during 2003-04. In field
      experimental ponds, mosquito abundance was significantly higher in the sewage
      effluent-treated water than in untreated control. As compared to untreated
      control, treated water had higher dissolved oxygen, total nitrogen, phosphorus,
      and turbidity, and it showed lower electrical conductivity, sulfate, carbonates,
      and bicarbonates. Diverse vegetation and invertebrate fauna as influenced by
      water quality may have contributed to higher mosquito breeding in the treated
      ponds. In laboratory studies, the treated water did not significantly affect the
      developmental rate, adult emergence, sex ratio, and overall mortality of Culex
      quinquefasciatus and Culex tarsalis, known vectors of encephalitides in southern
      California. However, the ovipositional response, especially of the former
      species, was numerically higher to the treated than to untreated control water.
      Besides smaller body size of 3rd/4th instars of both species, 4th-stage larvae of
      Cx. quinquefasciatus reared in the treated pond water weighed lighter than the
      control larvae.

PMID- 19852227
TI  - Evaluation of manhole inserts as structural barriers to mosquito entry into
      belowground stormwater systems using a simulated treatment device.
AB  - Belowground proprietary stormwater treatment devices can produce mosquitoes,
      including vectors of West Nile virus. Elimination of vertical entry points such
      as pick holes in manhole covers may reduce the number of mosquitoes entering and
      reproducing in these structures. Plastic manhole dish inserts were evaluated as
      structural barriers against mosquito entry through pick holes in a simulated
      stormwater treatment device. Inserts were 100% effective at preventing mosquito
      entry through covers when no other openings existed. In devices configured with
      an open lateral conveyance pipe, the addition of an insert under the cover
      reduced mosquito oviposition significantly. Subsequent trials to further
      elucidate mosquito entry through manhole covers found a significant positive
      correlation between increasing number of pick holes and mosquito oviposition.
      Results of the study suggest the potential for manhole dish inserts to decrease
      the number of mosquitoes entering belowground structures. The different available
      stormwater treatment systems and site-specific installations may, however,
      provide a much greater variety of possible alternate entry points for mosquitoes
      than was addressed in the current study. Further work is needed in field
      installations to quantify the significance of pick holes to mosquito entry and
      determine under what conditions, if any, manhole dish inserts would be most
      effective and appropriate.

PMID- 19852228
TI  - Survey of mosquito control knowledge, attitudes, and practices among county and
      municipal programs in Mississippi.
AB  - After Hurricane Katrina, 87 qualifying communities in Mississippi were issued
      contracts for disbursement of $2.8 million in federal funds for mosquito control.
      As part of this funding, a survey of mosquito control personnel was conducted to
      evaluate effectiveness of mosquito control programs at these 87 sites before and
      after disbursement of funds. Two nearly identical questionnaires requested
      information from county and municipal personnel about specifics for each of the
      sites, descriptions of operations and practices, information about mosquito
      control personnel, and information about attitudes of the respondents before and
      after implementation of the grant. Findings revealed that municipal mosquito
      control in Mississippi is conducted mostly by personnel in small town/city public
      works departments and not by contract to an outside agency. Also, mosquito
      control is composed mostly of routine spraying, based loosely on complaints, time
      of year, or other factors. For example, only 3% of participants in our survey
      utilized adult mosquito trapping surveillance data in their spray decisions, and
      only 11% said they dipped for larvae before treating standing water sites. In
      light of current environmental consciousness and chemophobia, much work remains
      to bring Mississippi mosquito control up to current scientific standards. The
      survey described herein was the first step, shedding light on specific problems
      encountered in mosquito control and providing public health and regulatory
      officials with guidance as to which issues to address first.

PMID- 19852229
TI  - First collection records of Aedes japonicus in Minnesota.
AB  - Aedes japonicus was first identified in the eastern United States during 1998 and
      has since spread to locations west of the Mississippi River. This species was
      found in Minnesota for the first time during 2007 at a tire recycling facility in
      Scott County and was identified during 2008 at 43 locations in 4 additional
      Minnesota counties south and east of the initial finding. These records document
      the presence of Ae. japonicus in 5 counties of southeastern Minnesota and
      indicate that the species overwinters locally.

PMID- 19852230
TI  - An unusual larval collection and survival of Orthopodomyia signifera in the
      presence of the predator Toxorhynchites rutilus septentrionalis.
AB  - From a discarded heavy-equipment tire (ca. 57 liter) at an industrial
      construction site, we collected 655 (86.0%) Orthopodomyia signifera, 23 (3.0%)
      Toxorhynchites rutilus septentrionalis, 17 (2.2%) Aedes japonicus japonicus, and
      67 (8.8%) Culex pipiens pipiens. Although larvae of Aedes albopictus and Aedes
      triseriatus were not collected from this container, both species were prevalent
      as host-seeking adults and readily collected as larvae from other containers at
      this site. Laboratory trials to test the survival of prey (Ae. albopictus, Cx. p.
      pipiens, or Or. signifera) in the presence of Tx. rut. septentrionalis showed
      that survival of prey larvae differed among species. Multiple comparisons
      revealed that Ae. albopictus had the lowest and Or. signifera the highest
      survival in the presence of Tx. rut. septentrionalis. Survival of Or. signifera
      and Cx. p. pipiens was not significantly different from one another, but both
      were different from Ae. albopictus. Further testing is warranted to test other
      factors responsible for differences in the interspecific relationship between Or.
      signifera and other species in tree hole communities.

PMID- 19852231
TI  - A model to assess the accuracy of detecting arboviruses in mosquito pools.
AB  - Vigilant surveillance of virus prevalence in mosquitoes is essential for risk
      assessment and outbreak prediction. Accurate virus detection methods are
      essential for arbovirus surveillance. We have developed a model to estimate the
      probability of accurately detecting a virus-positive mosquito from pooled field
      collections using standard molecular techniques. We discuss several factors
      influencing the probability of virus detection, including the number of virions
      in the sample, the total sample volume, and the portion of the sample volume that
      is being tested. Our model determines the probability of obtaining at least 1
      virion in the sample that is tested. The model also determines the optimal sample
      volume that is required in any test to ensure a desired probability of virus
      detection is achieved, and can be used to support the accuracy of current tests
      or to optimize existing techniques.

PMID- 19852232
TI  - Field evaluation of three botanical repellents against Psorophora ferox, Aedes
      atlanticus, and Aedes mitchellae.
AB  - Three botanical natural repellents, Swamp Buddy Bug Chaser (AI 12% plant-based
      essential oils), All Sport (AI plant-based essential oils, benzophenone-3,
      octinoxate, and octisalate), and Geraniol (AI 25% geraniol oil and lemongrass
      extract) were evaluated at a field site in Elkton, Florida, to determine the
      protection time provided against Psorophora ferox, Aedes atlanticus, and Ae.
      mitchellae. These three products provided different protection times against
      biting mosquitoes. Geraniol provided the longest protection time from mosquito
      bites (4 h), followed by All Sport (1.5 h) and Swamp Buddy Bug Chaser (1 h). This
      study provides the first information about botanical insect repellents against
      these floodwater mosquito species.

PMID- 19852233
TI  - Effect of repeated application of microbial larvicides on malaria transmission in
      central Cote d'Ivoire.
AB  - The effect of repeated applications of Bacillus thuringiensis var israeliensis
      (Bti) and B. sphaericus (Bs) on different entomologic parameters of malaria
      transmission was investigated in a village in central Cote d'Ivoire. The study
      area was monitored for potential mosquito breeding sites over a 7-month period.
      Microbial larvicides were applied once every 3 wk; first Bti (0.8 mg/liter),
      followed by Bs (10 mg/liter) 3-4 days later. Adult mosquitoes were collected
      inside and outside sentinel houses in 4 cross-sectional surveys using human
      landing catch. Repeated applications of Bti and Bs showed a decline in the biting
      rate of both Anopheles funestus and Anopheles gambiae. Moreover, the entomologic
      inoculation rate of An. funestus was significantly reduced (from 328 to 142, P =
      0.005), whereas that of An. gambiae remained stable. In conclusion, microbial
      larvicides might play a role in an integrated approach for malaria control.

PMID- 19852234
TI  - Insecticidal action of sodium anacardate from Brazilian cashew nut shell liquid
      against Aedes aegypti.
AB  - Aedes aegypti is the major vector of 1 of the most concerning arboviruses of the
      world, the dengue fever. The only effective way of reducing the incidence of
      dengue fever is to control the vector mosquito, mainly by application of
      insecticides to its breeding places. This study was aimed at assessing the
      insecticidal activity of sodium anacardate, isolated from Brazilian cashew nut
      shell liquid (CNSL), against the eggs, 3rd instars or pupae of Ae. aegypti. In
      addition, the acute toxicity of sodium anacardate to mice was also investigated.
      Sodium anacardate showed toxicity against Ae. aegypti eggs (median effective
      concentration [EC50] = 162.93 +/- 29.93 microg/ml), larvae (median lethal
      concentration [LC50] = 55.47 +/- 3.0 microg/ml) and pupae (LC50 = 369.78 - 52.30
      microg/ml). On the other hand, even at high dose (0.3 g/kg body weight), this
      compound did not cause any adverse effects on mice, suggesting that this compound
      is safe to mammals. Therefore, sodium anacardate may be a viable low-cost
      alternative to help combat Ae. aegypti.

PMID- 19852236
TI  - Psychohistory: creating a new discipline.

PMID- 19852235
TI  - Sentinel chicken coop modification for canopy-level arbovirus disease
      surveillance.
AB  - A pulley-block system for elevating sentinel chicken coops was designed to
      conduct mosquito-borne virus surveillance in the forest canopy. This modified
      design allows traditional captive sentinel bird cages to be hoisted easily to the
      desired height and lowered at regular intervals for routine maintenance and
      sampling of the flocks. The design specifications of this canopy system are
      modifications that can easily be incorporated to existing rabbit hutches used in
      ground-level captive sentinel systems.

PMID- 19852237
TI  - Evolution of childrearing and deMause's helping mode: an Australian case study.

PMID- 19852238
TI  - Modernization and dangerous women in Japan.

PMID- 19852239
TI  - The fear of infanticide and filicide in the emotional journey from Rosh Hashanah
      through Yom Kippur.

PMID- 19852240
TI  - The implications of denying fear and anxiety and idealizing victimizers.

PMID- 19852241
TI  - The European-American psychosis: psychohistoriographic perspective of
      contemporary Western civilization.

PMID- 19852242
TI  - [Iconography of embryos and fetuses in the treaties of delivery and anatomy from
      16th century till 18th century].
AB  - Leonardo', Eurakius' and Jacob Rueff's carved woods focus attention as they are
      sketches of foetuses in breech presentation. From the very beginning foetus is a
      little man made in the image of God in the works of Guillemeau, Mauriceau and
      Viardel. Later the liking for Baroque made the Putti, embryos with kindly faces
      created in Padua and Venice. Hunter's treatise finishes this picturesque review.

PMID- 19852243
TI  - [Louise Bourgeois (1563-1636): a midwife enters two worlds].
AB  - As a well-known practitioner Louise Bourgeois (1563-1636) lived experience of
      popular Parisian suburbs, middle-class and of the Court. As midwife of the Queen,
      she delivered Queen's six babies. One of them was the Dauphin who became King
      Louis XIII. Her habit of language and her vocabulary demonstrate that she was
      belonging to both of popular and educated worlds. Obstetrics was not free of
      Hippocrates and Galen conceptions and the theoretic weakness of her written works
      is noticeable while Pare then Guillemeau began the increasing knowledge of
      obstetrics.

PMID- 19852244
TI  - [Virtuousness and obstetrical practice in 19th century].
AB  - Childbirth was an almost secret process. In 1846 the mother or the husband of the
      parturient was admitted and on the other hand the nurses could follow the labour
      with the new positions. Interference of the sense of modesty for the patients as
      well as for the doctors greatly changed their relationship during the nineteenth
      century. Some situations are presented.

PMID- 19852245
TI  - [Return to the self-government of the midwife].
AB  - At first involved in private practice the majority of midwives became hospital
      practitioners as great changes of social behaviour occurred after 1945. After the
      creation of the Order of midwives they were directly subordinated to the medical
      profession. Their abilities were redefined in 1983; in 1995 they found again a
      part of autonomy and were admitted in the teaching of the Hospitals of the
      Universities.

PMID- 19852246
TI  - [Attitudes of medieval doctors on birth].
AB  - In the towns practitioners taught midwives whoses attendance is noticed in well
      known texts. Labour rooms might have been in lazarettos from the thirteenth
      century. Practice of delivery by Salerne's School was uncertain and heavy with
      superstition as the child birth's time was considered with fear of unknown forces
      and Chauliac's work seemed important during this period.

PMID- 19852247
TI  - [Stephane Leduc (1853-1939), from medicine to synthetic biology].
AB  - At the beginning of the XXth century, Stephane Leduc (1853-1939), physician and
      biologist in Nantes (France), believed that he created a new discipline: the
      synthetic biology. Using his own works on diffusion and osmotic growths, he
      considered that the structures obtained by him were very closed to living beings.
      In 1907, his conclusions were strongly criticized and his papers were refused by
      the Academie des Sciences de Paris, because they questioned spontaneous
      generations. This paper relates Leduc's experimental works and conclusions and as
      well analyses his analogical method.

PMID- 19852248
TI  - [The Treaty of diseases of the bones of the funds of the Museum Laennec de
      Nantes].
AB  - In this article, we analyse and give commentaries on one of the rare Guillaume
      Laennec's medical manuscripts. It is a treatise of bones' diseases, which is in
      fact a compilation of notes made, between 1769 and 1772, of Antoine Petit's
      lectures and other sources. This original document confirms at this time the
      emergence of rheumatology. It brings it obvious that the paediatrics assert their
      specific clinical forms. It illustrates the links between surgical and medical
      pathologies in the eighteenth century. It shows the old humoral theories to be
      the main obstacle in the way of understanding these pathologies. At last, it
      reveals that Guillaume Laennec is a member of a medical elite, and contributes to
      explain the beneficial effect he had on his nephew of genius, Rene Laennec.

PMID- 19852249
TI  - [Family practice in a rural environment in the west of France (1908-1920):
      chronicle of mortality].
AB  - This paper reports about a manuscript from Doctor Pelletier who accounted the
      causes of death rate in a village of the Vendee: pneumopathy, typhoid, diarrhoea
      linked to unhealthiness provoked by stagnant waters.

PMID- 19852250
TI  - [Maurice Sourdille, otologist of Nantes, famous and unknown].
AB  - Fenestration was the first surgical operation to improve deaf persons affected by
      otosclerosis. Its story is on a par with Maurice Sourdille's. Not only this
      author had perfected this surgery even before the use of antibiotics and
      audiometry but he was a forerunner in the field of ear surgery and in medical
      otology.

PMID- 19852251
TI  - [The amazing treatment of ringworm in a Nantes hospital at the beginning of the
      20th century].
AB  - In 1900, in Nantes, the ringworm was a real plague. Despite the very painful
      cares recovery could not be hoped before two years while the poor boys were
      roaming around far from school. At the Home St Jacques, a district for children
      suffering from ringworm and a department of electro-radiology were open where
      Doctor Gustave Bureau began to use X Rays to cure the ill hair and create a long
      lasting alopecia. The result was spectacular and patches disappeared in a few
      days. Besides three cases of radio dermatitis, there was no noticeable incident
      in spite of irradiation for twenty to twenty five minutes. The treatment has been
      used for about fifty years as it changed the life of the children till an
      effective drug. Then some studies showed the harmful long-term effects of such
      expositions to X rays.

PMID- 19852252
TI  - Motivation and justification: a dual-process model of culture in action.
AB  - This article presents a new model of culture in action. Although most
      sociologists who study culture emphasize its role in post hoc sense making,
      sociologists of religion and social psychologists tend to focus on the role
      beliefs play in motivation. The dual-process model integrates justificatory and
      motivational approaches by distinguishing between "discursive" and "practical"
      modes of culture and cognition. The author uses panel data from the National
      Study of Youth and Religion to illustrate the model's usefulness. Consistent with
      its predictions, he finds that though respondents cannot articulate clear
      principles of moral judgment, their choice from a list of moral-cultural scripts
      strongly predicts later behavior.

PMID- 19852253
TI  - Segregation, racial structure, and neighborhood violent crime.
AB  - Drawing on structural racism and urban disadvantage approaches, this article
      posits a broad influence of citywide racial residential segregation on levels of
      violent crime across all urban neighborhoods regardless of their racial/ethnic
      composition. Multilevel models based on data from the National Neighborhood Crime
      Study for 7,622 neighborhoods in 79 cities throughout the United States reveal
      that segregation is positively associated with violent crime for white and
      various types of nonwhite neighborhoods. Nonetheless, there is a lack of parity
      in violence across these types of communities reflecting the larger racialized
      social system in which whites are able to use their privileged position to reside
      in the most advantaged neighborhoods, while African-Americans and Latinos live in
      the most disadvantaged urban communities and therefore bear the brunt of urban
      criminal violence.

PMID- 19852254
TI  - Incest avoidance, the incest taboo, and social cohesion: revisiting Westermarck
      and the case of the Israeli kibbutzim.
AB  - During the past 50 years, a consensus has been forming around Edward
      Westermarck's idea that incest avoidance results from an aversion that develops
      when individuals are brought up in propinquity. The argument here presented
      counters this emerging consensus. Reexamining the case of the Israeli kibbutzim,
      the authors show that individuals who grew up in the kibbutzim's communal
      education system were in fact often attracted to their peers, and only rarely did
      they develop sexual aversion toward these peers. This article offers an
      alternative explanation to the problem of incest avoidance and the incest taboo,
      one that brings sociological factors back into the picture.

PMID- 19852255
TI  - Opening up and closing down: notes on the end of an asylum.
AB  - Deinstitutionalisation describes the process in which, throughout the western
      world, psychiatric hospitals discharged most of their patients and most often
      closed their doors. It coincided with an influential rethinking of the status of
      the mentally ill as citizens. At Wolston Park Hospital, Queensland's first and
      major psychiatric facility, opened in 1865, this was an extended process
      beginning in the 1930s that ended only in 2001. This paper considers how this
      happened, over what period of time, and with what kinds of impact on the
      institutional community. It makes use of oral histories collected among those who
      worked at the hospital as well as those who were its patients and clients.

PMID- 19852256
TI  - Seeking refuge: Why asylum facilities might still be relevant for mental health
      care services today.
AB  - This article reassesses the history of mental asylums in New South Wales, arguing
      that far from being 'cemeteries for the still breathing,' Victorian and Edwardian
      asylums served multiple purposes, providing genuinely therapeutic conditions for
      many patients, while warehousing chronic incurables and those without networks of
      support. Mental asylums in nineteenth century New South Wales rarely resorted to
      measures of restraint and seclusion and had a notable record of high rates of
      recovery and low rates of readmission. The marked institutional decline of the
      twentieth century that eventually prompted critics from many quarters to demand
      the closure of large asylums represented more a loss of faith in
      institutionalisation and the desire of psychiatrists to achieve higher status and
      more lucrative remuneration treating new middle class populations of neurotics
      than inherent flaws in the asylum ideal itself. Thus deinstitutionalisation
      policies were built on a fundamentally revisionist history that failed to
      consider the reality of care in these institutions, an insight that opens up
      opportunities to rethink the role and function of refuge in contemporary mental
      health policy.

PMID- 19852257
TI  - Australian asylum architecture through German eyes: Kew, Melbourne, 1867.
AB  - Kew Asylum in Melbourne, which by the 1890s was the largest in Australia, was
      planned in the 1850s, built on a prominent site in the 1860s, and opened in the
      early 1870s with accommodation for over 500 patients. Costing nearly 200,000
      pounds sterling and visible for miles, it was hailed by some as a 'palace.' Yet,
      in terms of international asylum architecture, the building was already out-of
      date when it received its first patients in 1871; within a few years it was being
      labelled 'backward.' Recently an article, published in a Berlin medical journal
      in 1867, has come to light that contains notes and a plan supplied by Kew's
      German architect. This enables us to study more closely the thinking behind the
      design of the asylum, the overseas models on which it was based and why it
      attracted so much criticism so quickly. Kew's problems reflect many of the
      fundamental shortcomings of mid-nineteenth-century asylum architecture in
      Australia and elsewhere.

PMID- 19852258
TI  - Families, insanity, and the psychiatric institution in Australia and New Zealand,
      1860-1914.
AB  - International historians have begun to challenge the view that the nineteenth
      century psychiatric hospital was a place of horrors and custody, and have shown
      that families were sometimes intimate with the institutions of the past, often
      participating in the process of institutional committal. This article explores
      the state of historical inquiry into families and insanity in Australia and New
      Zealand. It asserts that by re-examining patient cases we might find fresh
      insights into the dynamic between families and mental health. Through a close
      examination of archival sources, the article argues, we can see the presence of
      families 'inside' the asylum in several ways. Overall, the article suggests that
      institutional archives present both opportunity and risk for historians intent on
      discovering 'what happened' to the insane and their families.

PMID- 19852259
TI  - Working in the asylum: attendants to the insane.
AB  - Contemporary representations of nineteenth-century attendants were often
      negative, finding fault with both their character and conduct. Historians were
      inclined initially to agree, concluding that attendants were 'recruited from the
      dregs of society' and that asylum work was 'an occupation of last resort.' Other
      scholars argue that such conclusions rely too much on contemporary depictions.
      Taking Victoria as a case study, this article explores who attendants were and
      why they chose to do asylum work. Many of the attendants employed in Victoria's
      asylums were ordinary working people, recruited for their skills and experience,
      and for whom attending held considerable attractions. For some, indeed, attending
      became their life's work and an occupation whose reputation they felt was worth
      defending.

PMID- 19852260
TI  - Suicide, mental illness, and psychiatry in Queensland, 1890-1950.
AB  - This article contributes to the history of psychiatry by examining the practice
      of institutional and community psychiatry in early-twentieth-century Queensland.
      The source material for this article emerged from a larger project on the history
      of suicide and a review of the publications and lectures of the state's leading
      psychiatrist, John Bostock. The paper comes to several conclusions. First,
      asylums responded to the diversity of illnesses by making case-based judgments
      about the duration of treatment and the possibility of paroles. Many suicidal
      patients were not locked up for long periods if their ailments showed promise of
      alleviation. Second, we suggest that in the interwar period private practice was
      vibrant and worked interactively with traditional asylum committal. Third, even
      in rural areas there was awareness by the 1930s of urban-based alternatives to
      the asylums. Finally, we found evidence of attentive families who pursued several
      avenues of care for their loved-ones. Ultimately, the findings point to a complex
      mixed marketplace in psychiatric care during this time period.

PMID- 19852261
TI  - Divine service, music, sport, and recreation as medicinal in Australian asylums
      1860s-1945.
AB  - Australian asylum records (circa 1860 to circa 1945) demonstrate that medical
      staff went to great lengths to provide recreation to suitable patients. This
      article examines how the demarcation of Australian institutional spaces along
      gender divisions was also mirrored by the gender-specific recreational activities
      provided in purpose-built facilities. Using Australian examples I demonstrate how
      the main forms of recreation-that is divine service, music and dance, and sport
      were justified to governments on medical grounds. Some designated recreational
      spaces even offered select female and male patients the opportunity to mix under
      medical supervision. Recreation was therapeutic because of its psychological,
      physical, social, and moral benefits, and government authorities funded the
      construction of costly chapels, recreation halls, and sports grounds expressly
      for this medical purpose.

PMID- 19852262
TI  - Imprisoned in state care? Life inside Kew Cottages 1925-2008.
AB  - Established in 1887, Kew Cottages was Australia's oldest and largest specialised
      institution for people with intellectual disability. Kew Cottages was originally
      designed as a place of benevolent care and education for children. However its
      secluded location, adjacent to a 'Lunatic Asylum,' and its use of physical
      security measures resulted in its reputation as a place of incarceration. This
      viewpoint emerged through oral history testimony collected as part of the Kew
      Cottages History Project during 2005-08. Oral histories, which were recorded from
      people closely associated with Kew Cottages, reveal that despite the introduction
      of reforms in the mid-twentieth century to accord residents greater freedoms,
      poor living conditions, strict regimentation, violence, and abuse, all
      contributed to a prison-like environment within the institution.

PMID- 19852263
TI  - Advertising cadavers in the republic of letters: anatomical publications in the
      early modern Netherlands.
AB  - This paper sketches how late seventeenth-century Dutch anatomists used printed
      publications to advertise their anatomical preparations, inventions and
      instructional technologies to an international clientele. It focuses on
      anatomists Frederik Ruysch (1638-1732) and Lodewijk de Bils (1624-69), inventors
      of two separate anatomical preparation methods for preserving cadavers and body
      parts in a lifelike state for decades or centuries. Ruysch's and de Bils's
      publications functioned as an 'advertisement' for their preparations. These
      printed volumes informed potential customers that anatomical preparations were
      aesthetically pleasing and scientifically important but did not divulge the trade
      secrets of the method of production. Thanks to this strategy of non-disclosure
      and advertisement, de Bils and Ruysch could create a well-working monopoly market
      of anatomical preparations. The 'advertising' rhetorics of anatomical
      publications highlight the potential dangers of equating the growth of print
      culture with the development of an open system of knowledge exchange.

PMID- 19852264
TI  - [Importance should be attached to the causes of azoospermia].
AB  - Azoospermia is determined when no spermatozoa can be detected on high-powered
      microscopic examination of a pellet after centrifugation of the seminal fluid. A
      physician can initially identify the causes of azoospermia by an exhausted
      history and a complete physical examination. Men with testicular or pretesticular
      azoospermia should be offered genetic testing and measurement of serum sex
      hormones to exclude genetic abnormalities or hypogonadism. And the CFTR mutation
      test should be recommended to exclude the possibility of CF present in the
      offspring when azoospermia is related to CBAVD or primary epididymal obstruction.
      Testicular size, inhibin B levels and serum FSH concentration help to evaluate
      spermatogenesis of the testis, and diagnostic testicular biopsy can further
      distinguish obstructive causes from testicular failure in case of normal-sized
      testes. Vasography may be used to identify the site of obstruction, but only when
      reconstructive surgery is performed.

PMID- 19852265
TI  - [Changes of serum reproductive hormones with aging among healthy males in a
      community population of Hebei Province].
AB  - OBJECTIVE: To investigate the changes of serum reproductive hormones with male
      aging and to compare the differences in the hormone levels among different age
      groups or between township and rural males of the same age group. METHODS: Using
      cluster and stratified sampling, we recruited 434 healthy old and middle-aged (40
      69 years) males, 198 from the township and 236 from the rural communities. We
      determined the concentrations of serum total testosterone (tT), luteinizing
      hormone (LH) and sex hormone binding globulin (SHBG), free testosterone (fT), bio
      available testosterone (Bio-T), and obtained the testosterone secretion index
      (TSI) and free testosterone index (fTI). Meanwhile, we included fifty-nine 20-39
      years old males from the same communities in a control group. RESULTS: With the
      increase of age, the serum tT levels did not change significantly, while the
      levels of serum LH and SHBG increased, and those of fT, Bio-T, TSI and fTI
      decreased gradually. Statistically significant differences were found among the
      four different age groups in all the parameters of reproductive hormones (P <
      0.01), except in the serum tT level (P > 0.05). The serum tT level was not
      significantly correlated with aging and LH (P > 0.05). Serum LH and SHBG had a
      marked positive correlation with aging, and SHBG with LH (P < 0.01), while fT,
      Bio-T, TSI and fTI were negatively correlated with aging and the LH level (P <
      0.01). Serum LH, TSI and fTI showed statistical differences (P < 0.05), while fT
      and Bio-T exhibited extremely significant differences (P < 0.01) between the
      township and rural males in the 40 -49 yr group, and in the same age group, the
      increase rates of serum LH and SHBG and reduction rates of fT, Bio-T, TSI and fTI
      were higher in the rural men than in the township residents. However, the results
      were just the opposite in the 50 - 59 and 60 - 69 yr groups. CONCLUSION: The
      levels of serum LH, SHBG, fT, Bio-T, TSI and fTI changed with aging in a
      gradientmanner in the old and middle-aged males, but no significant changes were
      observed in the level of serum tT. There were statistical differences in many
      parameters of serum reproductive hormones among different age groups or between
      township and rural males.

PMID- 19852266
TI  - [Effects of smoking on sperm apoptosis and semen quality of adult males in the
      main urban area of Chongqing].
AB  - OBJECTIVE: To investigate the effects of smoking on sperm apoptosis and semen
      quality of healthy adult males in the main urban area of Chongqing. METHODS:
      According to the smoking habit, we divided 235 healthy adult males into a non
      smoking group (n = 89) and a smoking group (n = 146). Then we detected the
      routine semen parameters by the computer-assisted semen analysis system and
      obtained the parameters of sperm apoptosis (the ratios of AN-/PI-, AN+/PI-,
      AN+/PI+ and AN-/PI+ sperm) by flow cytometry combined with Annexin V-FITC/PI
      fluorescence staining. RESULTS: The rate of early apoptotic sperm (AN+/PI-) was
      higher in the smoking than in the non-smoking group ([8.1 +/- 5.1]% vs [6.8 +/-
      3.8]%; P = 0.039), but there were no significant differences between the two
      groups in the rate of late apoptotic sperm (AN+/PI+) ([5.6 +/- 5.2]% vs [5.5 +/-
      5.1]%; P = 0.87), as well as in such routine semen indexes as semen volume, sperm
      density, sperm motility, sperm vitality and normal sperm morphology (P = 0.30,
      0.82, 0.37, 0.81 and 0.84, respectively). CONCLUSION: The rate of early apoptotic
      sperm is higher in smokers than in non-smokers, suggesting that smoking may
      induce early damage to sperm cells. Compared with routine semen parameters, sperm
      apoptosis is a more sensitive biomarker to reflect smoking-induced damage to
      sperm.

PMID- 19852267
TI  - [Impact of rAd5-shRNA- PDE5A3 on cGMP in the smooth muscle cells of human corpus
      cavernosum].
AB  - OBJECTIVE: To investigate the effect of phosphodiesterase type 5 (PDE5) small
      interfering RNA (siRNA) on cyclic guanosine monophosphatethe (cGMP) in the smooth
      muscle cells of human corpus cavernosum, and to provide laboratory evidence for
      the application of the RNA interference (RNAi) technique for the treatment of
      erectile dysfunction. METHODS: The recombinant adenovirus rAd5-shRNA-PDE5A3
      expressing three pairs of specific shRNA was constructed successfully. The smooth
      muscle cells of human corpus cavernosum were divided into an experimental, a
      negative control and a blank control group, and transfected respectively with
      rAd5-shRNA-PDE5A3, adenovirus rAd5-mock and phosphate buffered saline. The
      concentration of cGMP was measured by radioimmunoassay at 24, 48 and 72 hours
      after transfection, and the effect of rAd5-shRNA-PDE5A3 was detected on the cGMP
      in the smooth muscle cells of the corpus cavernosum. RESULTS: The cGMP level in
      the smooth muscle cells of the corpus cavernosum was significantly higher in the
      rAd5-shRNA-PDE5A3 group than in the rAd5-mock control and blank control groups (P
      < 0.05), most significantly at 72 hours after transfection. CONCLUSION: The rAd5
      shRNA-PDE5A3 can obviously increase the cGMP level in the smooth muscle cells of
      human corpus cavernosum, and enhance the inhibition of the PDE5 gene.

PMID- 19852268
TI  - [Repair and functional reconstruction of the penis (a report of 62 cases)].
AB  - OBJECTIVE: To investigate the effects of surgery treatment on serious penile
      lesions and malformation. METHODS: Sixty-two patients, aged from 19 to 63 years
      old (mean 35 ys), were included in the study. Among them, 4 patients suffered
      from penis partial defection were respectively treated with restoring defective
      penis, penis lengthening and urethroplasty; three patients with penis completely
      missing were treated with penis reconstruction surgery; 22 cases with serious
      penile curvature were treated with the 16-dot plication technique (Lue's
      procedure); 15 cases with penile fracture were treated with conservative
      treatment for 1 case and with patch penis, corpus spongiosum, and deep penile
      dorsal vein ligation for 14 cases; 5 cases with post-operative complications of 3
      pieces of penile prosthesis, including the prosthesis perforating to the urethra,
      water pump failure, broken connection tube, erection angle < 60 degrees and
      failure to expansion the corpus cavernosum, were treated by taking out
      prostheses, urethral repair cracks, replacement of the prostheses, excision of
      fibrosis scar and re-implantation prostheses respectively. Four cases with penis
      complete amputation were treated with the penis replantation; three cases of
      avulsion injury were treated with the replantation and free flap skin; 6 with
      Paget's disease of penises were treated with the lesion free skin buried in the
      scrotum and penis. RESULTS: All these patients were followed up for 3 months to 4
      years, with the average of 9 months. Among the 4 cases of penis partial
      defection, 2 patients were satisfied with the penile appearance and sexual
      function; 1 got some satisfactory and 1 was unsatisfied. Three cases with the
      loss of the penis completely were satisfied with both the postoperative
      appearance and urination, and 1 was not satisfied. Twenty-two cases of penile
      curvature deformities were corrected, and one case was recurrence. Fourteen of
      the 15 patients with penile fracture were followed, and all got the restoration
      of sexual function. Among them, 5 cases with post-operative complications,
      including mild bending, algopareunia, subcutaneous induration, poor hardness and
      poor sexual pleasure, were not further treated, and another case lost; Five cases
      with post-operative complications of three-pieces penile prosthesis were treated
      successfully, and 4 of their spouses were satisfied with their sexual function
      after operation, only 1 of their spouse not satisfied. Among four cases with
      complete amputation of penis, two cases of penis were replanted successfully
      while two necrosis. Three cases with avulsion were treated with skin grafting
      successfully. All 6 cases with penile Paget's disease were followed for 2 -4
      years, and free skin grafts were all survival. One patient died of brain
      metastases 18 months after operation and five cases were disease-free survival.
      CONCLUSION: The patients should be treated based on the procedure of andrological
      and urological surgery, together with microsurgical, flap or skin graft
      technique. The urologist should design personalized surgical procedure. Most of
      the patient's penis shape and erectile dysfunction can be reconstructed by our
      procedures, but some patients can not achieve the desired appearance or function
      of penis. New approaches of the treatment ought to be developed to restore both
      of the shape and function for those severe injury of the penis.

PMID- 19852269
TI  - [Nandeshi: a powerful inhibitor of human acrosin activity].
AB  - OBJECTIVE: To evaluate the inhibitory effect of Nandeshi, an acrosin inhibitor,
      on human acrosin activity. METHODS: We collected sperm samples from 10 healthy
      fertile men and cultured them with Nandeshi at 30 degrees C for 5 minutes at the
      concentrations of 0. 100, 0.120, 0.144, 0.173, 0.207, 0.249, 0.299, 0.358 and
      0.430 mmol/L, with the controls treated with a well-known acrosin inhibitor N
      alpha-p-tosyl-L-lysine chloromethylketone (TLCK) at 150.0, 189.8, 213.6, 240.3,
      270.3, 304.1 and 342.1 mmol/L. Then we determined the residual activity of human
      acrosin by improved Kennedy assay. RESULTS: The residual activity of acrosin was
      negatively correlated with the Nandeshi concentration, and Nandeshi exhibited an
      inhibition rate about 800 times that of TLCK. CONCLUSION: Nandeshi has a powerful
      inhibitory effect on human acrosin, and improved Kennedy assay is a simple,
      practical and highly sensitive technique for the detection of human acrosin
      activity.

PMID- 19852270
TI  - [Establishment of recipient mouse model of stem cell transplantation into
      testicular seminiferous tubules and improvement of transplantation techniques].
AB  - OBJECTIVE: To establish a stable recipient mouse model for stem cell
      transplantation into seminiferous tubules and improve the traditional techniques
      for transplantation. METHODS: Sixty male ICR mice were equally divided into
      Groups A, B, C and D, and injected with Busulfan at 15 mg/kg, 30 mg/kg, 40 mg/kg
      and 0 mg/kg, respectively. The survival rate was recorded every day, and the
      testis weight and spermatogenesis of testicular tubules were determined at 4, 8
      and 12 weeks after the injection. We improved the stem cell transplantation
      technique and designed a new transplantation device, which connected the nozzle
      end, syringe and puncture needle by a three-way joint. The nozzle end was used
      for tentative injection, and the syringe for drawing and then injecting the cell
      suspension. RESULTS: Only one mouse in Group C died after the injection. At 4
      weeks after Busulfan treatment, the testis weight decreased apparently in Groups
      A, B and C, with significant differences from D (P < 0.05). The differences
      remained significant at 8 weeks (P < 0.05), except between Groups A and D (P >
      0.05), but at 12 weeks none of the first three groups showed any significant
      difference from Group D (P > 0.05). At 4 and 8 weeks, the rate of hollow
      seminiferous tubules was < 50% in Group A and > 50% in Groups B and C, and almost
      returned to normal at 12 weeks, with no significant differences among the three
      groups (P > 0.05), but it remained unchanged in Group D. The improved
      transplantation device increased the success rate (> 90%), lowered the donor cell
      loss (< 50 microl cell suspension needed for both testes) and shortened the
      process ( < 10 min for one testis). CONCLUSION: Intraperitoneal injection of
      Busulfan at 30 mg/kg is suitable for the establishment of the recipient mouse
      model of stem cell transplantation. The improved transplantation device and
      methods help promote the efficiency and success rate of the transplantation
      operation.

PMID- 19852271
TI  - [Observation of the changes in ventral prostatic microcirculation in castrated
      rats].
AB  - OBJECTIVE: Castrated rats exhibit significant shrinkage of the ventral prostate
      and apoptosis of prostatic cells, which can be attributed to the reduced blood
      supply to the prostate. But what causes the blood decrease in the prostate
      remains unknown. This study aims to explore the molecular mechanism of the
      changes in the microcirculation of the ventral prostate of rats following
      castration. METHODS: We randomized 24 male adult rats into 6 groups of equal
      number, and collected their ventral prostates at 0, 1/2, 1, 2, 3 and 7 d,
      respectively, after castration. Then we observed the changes of the microvessels
      under the transmission electron microscope, detected the apoptosis of endothelial
      cells by TUNEL, and determined the expressions of VEGF, endostatin, angiostatin
      and angiopoietin-2 by Western blot. RESULTS: The castrated rats showed dramatic
      changes in the microvessels of the ventral prostate, obvious apoptosis of the
      endothelial cells, down-regulated expression of VEGF, and up-regulated
      expressions of endostatin and angiostatin, while angiopoietin-2 remained
      unchanged. CONCLUSION: The decreased level of VEGF and increased levels of
      endostatin and angiostatin might underlie the mechanism of the changes in the
      microcirculation of the ventral prostate of rats following castration.

PMID- 19852272
TI  - [Effects of hyperbaric oxygen on tumor growth in the mouse model of LNCaP
      prostate cancer cell line].
AB  - OBJECTIVE: To assess the safety of hyperbaric oxygen in the treatment of
      radiation-induced hemorrhagic cystitis in patients with prostate cancer, and to
      investigate its effect on the growth of indolent prostate cancer in vivo.
      METHODS: Thirty severe combined-immunodeficient mice received subcutaneous
      injection of human prostate cancer LNCaP cells. Then they were randomized to an
      experimental and a control group and exposed to 20 sessions of hyperbaric oxygen
      and normobaric air, respectively, followed by a 4-week observation on the growth
      of the transplanted tumors and analyses of their histopathological features at 28
      days, including the volume, microvessel density (CD34), apoptosis markers (p53
      and p27 proteins) and the proliferation index (Ki-67) of the LNCaP tumors.
      RESULTS: On the 28th day after tumor vaccination, the tumor volume was (120 +/-
      7.9) mm3 in the HBO and (122 +/- 8.2) mm3 in the control group; the microvessel
      density and the expressions of Ki-67, p53 and p27 were 39.3 +/- 5.2, (78.1 +/-
      7.6)%, (40.4 +/- 6.2)% and (63.7 +/- 5.1)% in the former, and 36.2 +/- 4.9, (75.3
      +/- 8.4)%, (44.2 +/- 5.7)% and (61.5 +/- 5.5)% in the latter. There were no
      significant differences in all the indexes above between the two groups (P >
      0.05). CONCLUSION: Hyperbaric oxygen did not promote the growth of indolent
      prostate cancer in the murine model, nor did it have any significant effect on
      the new vessels.

PMID- 19852274
TI  - [Clinical features and minimally invasive treatment of prostatic utricle cyst].
AB  - OBJECTIVE: To investigate the clinical characteristics, diagnostic methods and
      minimally invasive treatment of prostatic utricle cyst. METHODS: We
      retrospectively analyzed the clinical data of 9 cases of prostatic utricle cyst,
      of whom 5 presented with frequent or urgent micturition, 3 with difficult
      urination or thinning urinary stream, and the other 1 with hemospermia. All the
      cases underwent ultrasonography and MRI. Transurethral cyst deroofing was
      performed for 3 of the patients with smaller cysts close to the prostatic
      urethra, and laparoscopic excision of the prostatic utricle was conducted for the
      other 6 with bigger cysts behind the prostatic urethra. RESULTS: The duration of
      transurethral cyst deroofing ranged from 30 to 50 min and intraoperative bleeding
      was 20 -70 ml; the mean time of laparoscopic excision of the prostatic utricle
      was 100 - 150 min and intraoperative bleeding was 30 -50 ml. All the patients
      were followed up for 3 - 12 months, which revealed normal penile erection and
      ejaculation, and no urinary tract irritation or difficult urination. CONCLUSION:
      Ultrasonography and MRI are excellent imaging modalities for accurate depiction
      of prostatic utricle cyst. Transurethral cyst deroofing is valuable for prostatic
      utricle cyst close to the prostatic urethra. Laparoscopic excision of the
      prostatic utricle, owing to its safety, effectiveness, minimal invasiveness,
      fewer complications and rapid recovery, can be used as the first option for the
      treatment of prostatic utricle cyst.

PMID- 19852273
TI  - [Retrospective analysis of the combined therapy of terazosin with chlormezanone
      for chronic prostatitis/chronic pelvic pain syndrome].
AB  - OBJECTIVE: To investigate the efficacy and safety of the alpha1-receptor
      inhibitor terazosin combined with chlormezanone in the treatment of chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 168 CPPS
      patients, aged 20 -50 (mean 32.9) years and with the disease course of 3 months
      to 7 years (mean 17 months), were equally randomized into a terazosin group (n =
      58), a chlormezanone group (n = 38) and a terazosin + chlormezanone (T + C) group
      (n = 72), and treated accordingly for 4 weeks. All the patients were scored on
      NIH-CPSI (National Institute of Health-Chronic Prostatitis Symptom Index) after
      the treatment and the therapeutic effects were compared among the three groups.
      RESULTS: Of the total number of patients, 159 completed the treatment and were
      evaluated, including 55 of the terazosin group, 35 of the chlormezanone group and
      69 of the T + C group. After the treatment, the NIH-CPSI scores of the three
      groups decreased from 24.05 +/- 3.02 to 16.15 +/- 3.25 (mean 7.90), from 23.43 +/
      3.58 to 17.51 +/- 3.08 (mean 5.92), and from 23.93 +/- 3.30 to 15.01 +/- 3.08
      (mean 8.92), respectively, with statistically significant differences from
      pretreatment (P < 0.05) as well as between the combined therapy group and the
      other two (P < 0.05). The adverse events included postural hypotension (17.1% in
      the terazosin group and 15.4% in the T + C group), dysspermatism (3.4% in the
      terazosin group only), lassitude, fatigue and anorexia (18.5% in the
      chlormezanone group and 12.6% in the T + C group). Nine of the patients failed to
      accomplish the treatment because of adverse events, 3 (5.2%) in the terazosin
      group, 3 (7.9%) in the chlormezanone group and 3 (12.6%) in the T + C group.
      CONCLUSION: Both terazosin and chlormezanone can relieve the symptoms in CP/CPPS
      patients and improve their life quality, but their combined use may produce a
      better efficacy than either terazosin or chlormezanone used alone.

PMID- 19852275
TI  - [Epidemiological changes of ED patients: investigations in 11 Chinese cities
      during the past 5 years].
AB  - OBJECTIVE: To investigate the epidemiological changes of erectile dysfunction
      (ED) patients in the past five years. METHODS: In 2003 and 2008, we conducted two
      questionnaire investigations on the epidemiological changes of ED outpatients in
      11 Chinese cities in such aspects as age, disease course, ED severity, smoking
      and drinking habits, accompanying hypertension, diabetes and coronary heart
      disease (CHD), and sexual intercourse satisfaction. RESULTS: According to the
      valid copies of the questionnaire collected (808 in 2003 and 858 in 2008), the
      age pattern of the ED patients hardly changed in the past five years, over 60%
      aged 30 - 50 years. Compared with the results obtained in 2003, the second
      investigation showed obvious increases in the following numbers of the ED
      patients: by 13% in those with longer disease courses (5 - 10 yr), from 24.1 to
      42.9% in those with moderate ED, from 20.4 to 29.9% in those with severe ED, by
      at least 10% in those with smoking and drinking habits, from 11.5 to 16.2% in
      those with hypertension, from 9.4 to 13.5% in those with diabetes, and from 57.6
      to 73.3% in those without sexual satisfaction, while the number of those with CHD
      did not change significantly. CONCLUSION: Increased unhealthy living habits and
      erectile function impairing diseases have added to the incidence and severity of
      ED. There is still much work to be done in the prevention and early treatment of
      ED.

PMID- 19852276
TI  - [Diagnosis and treatment of rare mixed prostatic carcinoma].
AB  - OBJECTIVE: To discuss the diagnosis and treatment of rare mixed prostatic
      carcinoma. METHODS: We retrospectively analyzed the clinical data of 6 cases of
      mixed prostatic tumor confirmed by surgery or transrectal ultrasound guided
      prostate biopsy, and reviewed the related literature. RESULTS: Three of the
      patients (2 with mixed small cell carcinoma and adenocarcinoma and 1 with
      adenosquamous carcinoma of the prostate) underwent palliative transurethral
      electrovaporization of the prostate (TUVP) and endocrine therapy, but all died
      within 7 - 10 months. The other 3 (2 with adenosquamous carcinoma and 1 with
      carcinosarcoma of the prostate) received cystoprostatectomy, urinary diversion,
      pelvic lymphadenectomy and radiation therapy, and survived for more than 12
      months, with 2 of them still under the follow-up observation. CONCLUSION: Mixed
      prostatic carcinoma behaves aggressively with poor prognosis, of which the
      diagnosis relies on meticulous pathological examination and immunohistochemical
      techniques, and the most effective treatment is radical surgery.

PMID- 19852277
TI  - [Minute dose of tadalafil for nocturnal penile tumescence].
AB  - OBJECTIVE: To investigate the efficacy of tadalafil on nocturnal penile
      tumescence (NPT). METHODS: Thirty-four patients with organic erectile dysfunction
      (ED) were treated with oral tadalafil at the dose of 10 mg/3 d before bedtime. A
      month later, 14 of the patients were observed for NPT by nocturnal
      electrobioimpedance volumetric assessment (NEVA). RESULTS: The parameters of
      erectile function significantly improved in the 14 patients (P < 0.05).
      CONCLUSION: Oral administration of minute dose of tadalafil can improve NPT in
      organic ED patients.

PMID- 19852278
TI  - [Primary Burkitt lymphoma of the seminal vesicle: a case report and review of the
      literature].
AB  - OBJECTIVE: To investigate the clinicopathological features of primary Burkitt
      lymphoma of the seminal vesicle. METHODS: We reported the clinical
      characteristics, histological changes and the results of immunohistochemical
      staining and molecular in situ hybridization of 1 case of primary Burkitt
      lymphoma of the seminal vesicle. We also reviewed the related literature and
      studied the pathomorphological characteristics and differential diagnosis of the
      tumor. RESULTS: The characteristic manifestations of the patient were frequent
      micturition with dysuria, followed by inguinal lymphadenectasis 2 months later.
      Medical imaging showed a diffuse and monotonous infiltration of neoplastic cells
      with scanty cytoplasm and a few mitosis images. Microscopy displayed a starry sky
      pattern. The tumor cells were positive for CD10, CD20, CD79alpha, Bcl-6 and EBER
      in situ hybridization, but negative for CD3, CD6 and Cyclin D1. The Ki-67 index
      was > 95%. CONCLUSION: Primary Burkitt lymphoma of the seminal vesicle is a very
      rare tumor with aggressive behavior. The pathological diagnosis of the tumor
      depends on histopathological examination and immunohistochemical techniques.
      However it should be differentiated from diffuse large B-cell lymphoma,
      lymphoblastic lymphoma and small cell carcinoma of the seminal vesicle or
      prostate gland.

PMID- 19852279
TI  - [Incidences of erectile dysfunction and retrograde ejaculation after suprapubic
      prostatectomy and transurethral resection of the prostate in Chinese men: a meta
      analysis].
AB  - OBJECTIVE: To compare suprapubic prostatectomy (SPPC) with transurethral
      resection of the prostate (TURP) in inducing erectile dysfunction (ED) and
      retrograde ejaculation (RE) in Chinese men. METHODS: We retrieved all the case
      controlled studies on the comparison of SPPC and TURP in inducing ED and RE by
      searching Medline and Chinese Journal Full-text Database (CJFD) (up to January
      2009), screened the eligible literature according to the selection and exclusion
      criteria, and performed meta-analyses on the included studies using the software
      Revman 4. 2. RESULTS: Eight eligible reports were identified in this study,
      including 515 cases of SPPC and 462 cases of TURP. The SPPC group showed a little
      higher incidence of ED than the TURP group (pooled OR: 1.34; 95% CI, 0.97, 1.85),
      with no statistically significant difference (P > 0.05), while the latter
      exhibited a significantly higher incidence of RE than the former (pooled OR:
      0.58; 95% CI, 0.44, 0.76, P < 0.05). CONCLUSION: There is no significant
      difference between the incidence of ED after SPPC and that after TURP in Chinese
      men, but the latter may induce a much higher rate of retrograde ejaculation than
      the former.

PMID- 19852280
TI  - [Research progress in the in vitro culture of testicular spermatogenic cells].
AB  - The production of sperm is a very complicated and orderly process, which involves
      the proliferation and differentiation of cells. The in vitro culture of
      spermatogenic cells includes tissue culture and cell culture. This study focuses
      on the advances in the in vitro culture of spermatogenic cells, testicular tissue
      culture and their culture conditions, and sums up the advantages and
      disadvantages of various culture methods, in an attempt to find the best method
      for differentiating spermatogenic cells in vitro and make the culture of
      spermatogenic cells an important means of treating male infertility.

PMID- 19852281
TI  - [Human zona pellucida glycoproteins and their binding to sperm].
AB  - Human zona pellucida (hZP) plays a critical role in the recognition, binding of
      sperms and oocytes, induction of acrosomal exocytosis, and avoidance of
      polyspermy. Human ZP is composed of four glycoproteins designated as hZP1, hZP2,
      hZP3 and hZP4. This paper reviews the actions of native hZP or recombinant hZP on
      acrosomal exocytosis and sperm-ZP binding.

PMID- 19852283
TI  - [Moving towards a global definition of myocardial infarction].

PMID- 19852282
TI  - [Clinical efficacy of Shengjing capsule on patients with oligoasthenospermia].
AB  - OBJECTIVE: To investigate the clinical effect of the Chinese medicinal
      preparation Shengling Capsule on patients with oligoasthenospermia. METHODS: A
      total of 270 male patients with infertility induced by oligoasthenospermia were
      equally divided into a treatment and a control group, the former medicated with
      Shengling Capsule at the dose of 1.6 g tid, and the latter given Vit E at 50 mg
      tid, both for a course of 12 weeks. Then we analyzed the changes in the
      patients'seminal parameters and the pregnancy of their wives. RESULTS: After 12
      weeks of medication, both the seminal parameters of the patients and pregnancy of
      their wives were remarkably improved, with extremely significant differences from
      pre-treatment and the control (P < 0.01). CONCLUSION: Shengjing Capsule can
      improve sperm motility and vitality as well as sperm count. With few adverse
      effects, it can be used as a safe and effective therapeutic for male infertility
      induced by oligoasthenospermia.

PMID- 19852284
TI  - [Problems and countermeasures of Chinese and Western medical treatment of chronic
      hepatitis B].

PMID- 19852285
TI  - [Fifty years of experience on integrative medical treatment of polycystic ovarian
      syndrome].

PMID- 19852286
TI  - [Genetic mechanism of polycystic ovarian syndrome].

PMID- 19852287
TI  - [Exploration into the pathogenesis and treatment of polycystic ovarian syndrome
      from viewpoints of menstrual disorder and phlegm accumulation in uterus].

PMID- 19852288
TI  - [A multi-centered randomized double-blinded controlled clinical study on efficacy
      of gulling pa'an capsule in treating Parkinson's disease].
AB  - OBJECTIVE: To objectively evaluate the clinical efficacy of Gulling Pa'an Capsule
      (GPC), a Chinese medicine, in treating Parkinson's disease (PD). METHODS:
      According to the good clinical practice (GCP) principle, a multi-centered, double
      blinded, layered, randomized and grouping-controlled clinical trial was carried
      out from May 2002 to January 2005 on 242 PD patients. Among them, 53 patients who
      had never received levodopa were randomized into two groups, 28 in group A
      treated with GPC, and 25 in group B treated with placebo; patients who had
      received levodopa were assigned depending on the Hoehn & Yahr (H-Y) grade, to 4
      groups, 75 and 19 of grade 1.5 -3 in group C and E, respectively, 79 and 16 of
      grade 4 in group D and F, respectively, patients in group C and E were treated
      with GPC and Levodopa, and those in group D and F treated with placebo and
      Levodopa for control. The treatment course was 12 weeks for all. Changes of
      unified Parkinson's disease rating scale (UPDRS) II/III scores in comparing with
      the baseline were assessed. For the groups C, D, E and F, the dosage of levodopa
      administered was also recorded. Meanwhile, the blood pressure, pulse rate, blood
      and urine routine, liver and renal functions, electrocardiogram (ECG) and adverse
      reactions were monitored as the indices for safety supervise. RESULTS: (1) After
      treatment, symptoms were markedly improved in 1 out of the 28 patients in group A
      and improved in 11, the markedly improving rate was 3.6% and the improving rate
      39.3%; while in group B, the corresponding outcomes were 0 (0/25) and 28.0%
      (7/25) respectively, showing insignificant difference between the two groups.
      UPDRS scores, including the total, II and III scores were all significantly
      lowered in group A after treatment (P < 0.01, P < 0.05); while in group B,
      significant lowering only showed in terms of UPDRS III (P < 0.05); but the inter
      group comparison of the changes in all the three items showed no significant
      difference. (2) The significant improving rate was 12.0% (9/75) and improving
      rate 48.0% (36/75) in group C, while those in group D, 12.7% (10/79) and 24.1%
      (19/79) respectively, the efficacy in group C was better (P < 0.05). The items of
      3 UPDRS scores in groups C and D were all significantly lowered after treatment
      (P < 0.01), and the lowering in group C was more significant in terms of the
      total and II scores (P < 0.05). (3) The significant improving rate was 5.3%
      (1/19) and improving rate 36.8% (7/19) in group E, while in group F 0% (0/19) and
      25.0% (4/16), respectively, showing insignificant difference between them; UPDRS
      scores lowered significantly in the two groups after treatment (P < 0.01), also
      showed no statistical significance in comparison (P > 0.05). (4) The dosage of
      Levodopa required in groups C and E was significantly reduced after treatment (P
      < 0.05), while in groups D and F, it was unchanged (P > 0.05); yet, the further
      analysis displayed that significant reduction only presented in group C (P <
      0.05), not in the other three groups. CONCLUSIONS: The overall efficacy of
      levodopa in combined with GPC for treating PD patients of H-Y grade 1.5 -3 is
      significantly higher than that of levodopa alone. GPC shows obvious effects in
      improving patients' motor syndrome and the quality of life; as used in combining
      with levodopa, the dosage of levodopa required could be reduced.

PMID- 19852289
TI  - [Advantages of Chinese medicine for treatment of blood sugar and lipid metabolic
      disorders in patients with polycystic ovarian syndrome].
AB  - OBJECTIVE: To study the advantages of Chinese medicine (CM) in treating insulin
      resistance and disorders of glucose and lipid metabolism in patients with
      polycystic ovarian syndrome (PCOS), and to explore its underlying mechanisms.
      METHODS: One hundred PCOS patients were assigned to three groups: 40 patients in
      the CM group treated by CM, 30 in the WM1 group treated by metformin, and 30 in
      the WM2 group treated by cyproterone. Before treatment and at 3 cycles and 6
      cycles after treatment, changes of body mass index (BMI), fasting serum insulin
      (FINS) and fasting blood sugar (FBG) levels as well as lipid spectrum were
      measured and the homeostasis model of insulin resistance (HOMA-IR) was
      calculated. Meanwhile, the recovery of ovulation was observed. RESULTS: There
      were 30, 22 and 23 patients in the CM, WM1 and WM2 group respectively completed
      their 6-month treatments. Levels of FINS, FBG, HOMA-IR, total cholesterol (TC)
      and low-density lipoprotein cholesterol (LDL-C) were lowered and high-density
      lipoprotein cholesterol (HDL-C) level increased in the CM group after 6-month
      treatment, showing significant difference as compared with the baseline (P <
      0.05), and the difference in comparing with the WM2 group was statistically
      significant in terms of MBI, FINS, FBG, HOMA-IR, TC and LDL-C (P < 0.05). The
      ovulation rate was 53.3% (16/30) in the CM group, 27.3% (6/22) in the WM1 group
      and 21.7% (5/23) in the WM2 group, comparison between them showed a significant
      difference between the CM group and the WM2 group (P < 0.01). CONCLUSION: CM is
      effective for the treatment of PCOS in improving insulin resistance, adjusting
      blood sugar and lipids levels and recovering ovulation.

PMID- 19852291
TI  - [Relationship between Chinese medicine pattern with blood levels of sex hormone,
      lipid and glucose in climacteric women patients with hypertension].
AB  - OBJECTIVE: To find the objective indices for traditional Chinese medicine (TCM)
      pattern identification in women patients with climacteric hypertension (CH) by
      exploring the relationship between TCM pattern with blood levels of sex hormone,
      lipid and glucose. METHODS: TCM syndrome differentiation was made in 75 women CH
      patients, 43 as yin-deficiency with inner dryness pattern (YDD) and 32 as non
      YDD, and correlation analyses were conducted on TCM patterns and blood levels of
      estradiol (E2), lipids and glucose. RESULTS: Besides the level of E2 in YDD was
      lower than that in non-YDD [(112.26 -/+ 66.81) pmol/L vs (146.69 +/- 83.59)
      pmol/L, P < 0.05), no difference between the two patterns was found in the other
      indices measured (P > 0.05). Further subunit analysis showed that in patients
      with CH grade 1, blood levels of total cholesterol (TC), high density lipoprotein
      (HDL) and apoprotein A-I (ApoA-I) were higher in the 13 patients of YDD than
      those in the 9 of non-TDD (P < 0.05); in patients with CH grade 2, levels of E2,
      progesterone (T), HDL and ApoA-I were lower but level of follicle stimulating
      hormone (FSH) was higher in the 20 YDD than those in the 10 non-YDD (all P <
      0.05); while in patients with CH grade, no statistically significant difference
      was shown between 3 patients of 10 with YDD and 13 with non-YDD in all the
      indices measured (P > 0.05). CONCLUSION: Blood level of E2 shows different
      characteristics between CH patients of YDD and non-YDD patterns, suggesting that
      it may provide some help to syndrome micro-differentiation, and taking it as an
      objective index for syndrome typing of climacteric hypertension in female is
      considerable.

PMID- 19852290
TI  - [Effect of bushen zhuanggu granule on the gonadal hormone and blood lipid
      metabolism in climacteric women].
AB  - OBJECTIVE: To investigate the effect of Bushen Zhuanggu Granule (BZG) on the
      gonadal hormone, blood lipids, serum level of nitric oxide (NO) and free oxygen
      radical (FOR) in climacteric women. METHODS: Climacteric women were randomized
      according the digital table into the CM group (188 cases) and the WM group (189
      cases). They were treated by BZG and Premarin plus Depogeston respectively for 2
      years. The therapeutic effect on patients' symptoms and changes of blood lipids,
      gonadal hormones, NO, superoxide dismutase (SOD) and malonaldehyde (MDA) were
      observed. RESULTS: There were 53 women in the CM group and 96 in the WM group
      dropping out in the 2-year follow-up period, the difference between them was
      significant (P < 0.01). The obvious and effective rates in the CM group were
      36.30% (49/135), 82.96% (112/135), and in WM were 30.11% (28/93), 73.12% (68/93),
      the difference between the two group was significant (P < 0.05). The score of
      complaint was significantly lower in both groups (P < 0.05, P < 0.01), and the
      effect was more obvious in the CM group (P < 0.01). Effects on gonadal hormones
      and blood lipids were significantly improved in both groups after treatment (P <
      0.05); comparison between groups showed the superiority of WM in increasing
      estrogen (P < 0.05), Blood levels of NO and SOD increased and MDA decreased in
      both groups after 1- and 2-year treatment (P < 0.05 or P < 0.01), showing no
      significant inter-group difference (P > 0.05). No evident adverse reaction was
      found in the routine tests on blood, urine and stool, hepatic and renal functions
      and electrocardiogram examined once every 6 months. CONCLUSION: BZG can
      effectively restore the disordered indices of gonadal hormones, blood lipids, NO,
      and SOD in climacteric women, with the efficacy equivalent to the effect of
      hormone replacement therapy, but it is more safe and inexpensive.

PMID- 19852292
TI  - [Effect of qingyi decoction in preventing post-endoscopic retrograde
      cholangiopancreatography pancreatitis and hyperamylasemia].
AB  - OBJECTIVE: To explore the preventive effect of Qingyi Decoction (QYD) on post
      endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and
      hyperamylasemia. METHODS: One hundred and twenty-five patients scheduled to
      receive ERCP were randomized by the digital table into three groups, two were
      medicated respectively with QYD (39 cases) and octreotide (42 cases), the other
      one was untreated for control (44 cases). Changes of blood levels of amylase, C
      reactive protein (CRP), and interleukin-10 (IL-10), as well as the incidence of
      pancreatitis and hyperamylasemia was observed and compared. RESULTS: The 4 h and
      24 h post-operational blood amylase (U/L) was 132.03 +/- 75.29 and 153.15 +/-
      78.69 in the QYD group, and 134.74 +/- 22.24 and 148.50 +/- 79.37 in the
      octreotide group, all were significantly lower than those in the control group
      (241.27 +/- 137.04 and 286.89 +/- 133.77), respectively. The 24 h CRP (mg/L) in
      both QYD and octreotide group (11.05 +/- 3.57 and 12.48 +/- 3.80) was also lower
      than that in the control group (17.70 +/- 4.93, P < 0.05), while the 24 h IL-10
      (ng/L) in the QYD group (105.00 +/- 31.85) was higher than that in the octreotide
      group (77.98 +/- 33.13) and the control group (75.98 +/- 30.99) respectively. The
      incidence of pancreatitis in the QYD, octreotide, and the control group was 2.6%,
      0 and 11.4%, that of hyperamylasemia in them 28.2%, 21.4%, and 56.8%,
      respectively. The occurrence rate of hyperamylasemia was lower in the QYD group
      and the octreotide group than in the control group (P < 0.05). CONCLUSION: QYD
      could lower CRP and up-regulate IL-10 level, restrain the inflammation reaction
      and reduce the blood amylase level in the post-ERCP period, thus reducing the
      incidence of hyperamylasemia.

PMID- 19852293
TI  - [Effect of guishen zhiyang recipe for treatment of patients with senile pruritus
      of blood-deficiency and Gan-hyperactive syndrome type and its impact on stem cell
      factor and dynorphin].
AB  - OBJECTIVE: To explore the mechanism of Chinese medicinal therapy for nourishing
      blood and softening Gan in treating senile pruritus through observing the impact
      of Guishen Zhiyang Recipe (GZR) on serum levels of stem cell factor (SCF) and
      dynorphin (DYN) in patients suffered from the disease of blood-deficiency and Gan
      hyperactive syndrome type (BDGH). METHODS: Sixty patients with senile pruritus
      were equally randomized into two groups, the patients in the treated group (33
      cases) were treated by GZR, and those in the control group (28 cases) were
      treated by Fuyang Granule, all for 8 weeks. Changes of symptoms and skin lesions
      as well as blood levels of SCF and DYN were observed before and after treatment.
      RESULTS: Three patients were rejected from the treated group. Twenty patients in
      the treated group were cured after treatment, the cure rate being 66.7%, which
      was significantly higher than that in the control group (10 patients, 35.7%, P <
      0.05). Levels of SCF and DYN in the treated group significantly lowered after
      treatment (all P < 0.01), and were lower than those in the control group (P <
      0.05 and P < 0.01, respectively). CONCLUSION: GZR shows favorite effect in
      treating senile pruritus of BDGH type and it may be achieved by regulating SCF
      and DYN levels to improve the pruritus associated inflammatory media.

PMID- 19852294
TI  - [Clinical and experimental study on effect of qinbal ointment in treating
      psoriasis in the active stage of blood-heat syndrome type].
AB  - OBJECTIVE: To investigate and compare the efficacy and safety of two kinds of
      Qinbai ointment prepared conventionally and finely (C-QBO and F-QBO) in treating
      psoriasis in the active stage of blood-heat syndrome type, and to observe their
      influences on vaginal epithelial cell mitosis, also on keratinization of caudal
      flakes in mice. METHODS:  CLINICAL OBSERVATION: Adopting randomized, single
      blinded, controlled design, 93 patients administered orally with Liangxue Huoxue
      Decoction were randomized into three groups treated externally with C-QBO, F-QBO
      and white vaseline respectively, applied twice a day for 8 weeks. The safety was
      checked and the changes of modified psoriasis area severity index (PASI), as well
      as the conditions of skin lesions (size, erythema, infiltration, squama, and
      itching) and symptom improving time were compared. Experimental study 1: Mice
      were randomized into the model group, the C-QBO group, the F-QBO group and the
      blank group, 7 in each group. Their vaginal epithelial cell mitosis indices were
      compared after 3 days of treatment with corresponding remedies. Experimental
      study 2: Mice were randomized into the C-QBO group, the F-QBO group and the blank
      group, 7 in each group. After the mice had been treated with corresponding
      remedies for 28 days, the granular layer formation in their caudal scales was
      compared. RESULTS:  CLINICAL OBSERVATION: The markedly effective rate was 63.3%
      (25/30) in the C-QBO group, 66.7% (20/30) in the F-QBO group, and 36.7% (11/30)
      in the control group. No statistical difference was showen between the two QBO
      treated groups (P > 0.05), but that in both of them was significantly different
      from that in the control group (P < 0.05). PASI scores lowered after treatment in
      all the three groups (P < 0.01), but the improvement in the two QBO groups was
      better than that in the control group (P < 0.05); the conditions of skin lesion
      were improved in all groups, but the improvements were more significant in the
      two QBO groups in terms of squama, infiltration and itching (P < 0.05), in
      aspects of improving time on erythema, infiltration and itching, especially the
      itching, F-QBO was superior to the C-QBO. Experimental study 1: The mitosis index
      in both QBO groups was lower than that in the blank group and the model group (P
      < 0.01). Experimental study 2: Number of scales with granular layer formation was
      higher in the two QBO groups than in the blank group (P < 0.01). CONCLUSION: C
      QBO and F-QBO can effectively relieve the skin lesion of psoriasis patients in
      the active stage of blood-heat type, and they could also promote the formation of
      epithelial granular layer in the caudal scales of mice.

PMID- 19852295
TI  - [The protective roles of tiangui gengnian soft capsule on brain in aged female
      rats and its mechanism].
AB  - OBJECTIVE: To investigate the brain-protective and anti-aging effects and the
      mechanism of action of Tiangui Gengnian Soft Capsule (TGSC), a Chinese herbal
      preparation composed of sea buckthorn fatty acids. METHODS: Sixteen-month-old
      female rats were administered via gastric perfusion with low, medium and high
      doses (0.72 g/kg, 1.80 g/kg and 4.5 g/kg) of TGSC for 180 days. The 3-month and
      22-month old rats were taken as controls. Expression of estrogen receptor
      beta(ERbeta), tyrosine hydroxylase (TH), granulocyte colony-stimulating factor (G
      CSF) and vascular endothelial growth factor (VEGF) in the brain of rats were
      observed and analyzed using immunohistochemical technique, and changes in the
      number of neurons and glial cells were counted with Nissl's staining. RESULTS:
      Immunohistochemistry showed the number of ERbeta- and TH-positive neurons in the
      hypothalamus was significantly higher (P < 0.01 and P < 0.05), G-CSF-positive
      astrocyte stain was much weaker (P < 0.01) and the expression of VEGF-positive
      cerebral vessel was stronger (P < 0.05) in the TGSC treated groups than those in
      the control. Nissl's staining showed no significant difference in the number of
      neurons and glial cells among groups. CONCLUSION: TGSC could up-regulate the
      expressions of ERbeta, TH and VEGF in the brain of aged female rats, modulate the
      responsibility of astrocyte and its G-CSF expression, suggesting that TGSC may
      have certain neuro-protective and anti-aging effects.

PMID- 19852296
TI  - [Of berberine and puerarin on dexamethasone-induced insulin resistance in porcine
      ovarian thecal cells].
AB  - OBJECTIVE: To explore the direct contribution of dexamethasone (Dex) for insulin
      resistance inducing in thecal cells and effects of berberine (Ber) and puerarin
      (Pue). METHODS: Ovarian thecal cells from porcine follicles were isolated and
      cultured in vitro. Insulin resistance of thecal cells was induced by Dex
      treatment for 48 h. Then the glucose utilization ratio of thecal cells was
      detected. Meanwhile, the effects of Ber and Pue on insulin signal transmission
      and steroid hormones synthesis were determined by RT-PCR and Western blotting.
      RESULTS: (1) After being treated by Dex for 48 h, the [3-3H] -glucose uptake in
      cells was lowered by about half, and the glucose content in supernate increased
      for about 1/3. (2) The RT-PCR and Western blotting showed that levels of insulin
      receptor substrate-1 (IRS-1), mRNA and protein expression of glucose transporter
      4 (GLUT4) lowered, peroxisome proliferator-activated receptor -gamma(PPARgamma)
      and cytochrome P450 17 hydroxylase (CYP17) mRNA or protein expression increased
      in the model cells. However, the changes of above insulin signal molecules and
      CYP17 expression were inversed significantly after treated with Ber and Pue for
      48 h. (3) As compared with the control, in the model cells, levels of
      testosterone (T, microg/mL) was higher (0.82 +/- 0.20 vs 0.38 +/- 0.01, P <
      0.05), while after Ber and Pue treatment it was 0.44 +/- 0.24 and 0.45 +/- 0.21
      respectively, all lower than that in the model cells (P < 0.05). No significant
      change of serum progesterone was found in all groups (P > 0.05). CONCLUSIONS:
      After insulin resistance has been induced, the androgen synthetic capacity of
      thecal cells enhanced significantly. Ber and Pue could lower the degree of
      insulin resistance and the androgen synthesis in the model cells, displaying the
      favorable prospect of the two insulin sensitizing agents for the treatment of
      polycystic syndrome.

PMID- 19852297
TI  - [Effects of bushen zhuyun recipe on protein expressions of estrogen receptor,
      progesterone receptor and integrin alpha5 and beta3 in endometrium of rats at the
      implantation stage].
AB  - OBJECTIVE: To observe the effects of Bushen Zhuyun Recipe (BZR) on protein
      expressions of estrogen receptor (ER), progesterone receptor (PR) and integrin
      alpha5 and beta3 in endometrium of rats at the implantation stage, for exploring
      the possible mechanism of the recipe in treating luteal phase defect (LPD)
      infertility. METHODS: Female SD rats were randomly divided into 6 groups, the
      blank group, the model group, the WM group treated by Western medicine, and the
      three BZR groups treated by low-, middle- and high-dose BZR respectively. Rats
      were made to pregnancy and sacrificed at the implantation stage, their middle
      segment of uterus, about 1 cm in length was gotten for detecting the protein
      expressions by Western blot. Results The protein expressions of endometrial ER
      and PR were significantly higher, while those of integrin alpha5 and beta3 were
      significantly lower than those of the control group (P < 0.05). The protein
      expressions of endometrial ER and PR were significantly lower, but those of
      integrin alpha5 and integrin beta3 were higher in rats treated by middle- and
      high- dose BZR than those in model rats (P < 0.05). CONCLUSION: BZR can raise the
      receptivity of rats' endometrium through down-regulating the expressions of ER,
      PR and increasing the protein expression of integrin alpha5 and beta3 in
      endometrium and thus to enhance the pregnant rate.

PMID- 19852298
TI  - [Inhibitory effects of puerarin on invasion and metastasis of oophoroma cells HO
      8910].
AB  - OBJECTIVE: To investigate the inhibitory effect of puerarin on invasive and
      metastatic abilities of tumor cells, and its possible mechanism through observing
      its impacts on the migratory, adhesive and invasive capacities of human oophoroma
      cells HO-8910 to the artificial recombined basement membrane. METHODS: Expression
      of estrogen receptor (ER) in HO-8910 cells was detected using PCR assay. Effects
      of puerarin on HO-8910 proliferation was detected with MTT assay; on its adhesion
      potential was tested with cell-matrigel adhesion assay, and on invasive and
      migratory capacities were measured with Transwell matrigel invasion assay and
      Transwell motility assay respectively. RESULTS: ER was positively expressed in HO
      8910 cells. After being treated with 20 micromol/L puerarin for 12 h, the
      adhesive test showed that OD value in the tested group was significantly lower
      than that in the control (P < 0.01), the inhibiting rate reached 50.63%; and the
      Transwell assay showed a significant lowering of penetrated cells (P < 0.01), the
      inhibition rate for invasion was 38.59% and that for motility migration 40.63%.
      The number of penetrated cells was lower in the group intervened with combination
      of Puerarin and estrogen than in the group intervened with estrogen alone, 33.40
      +/- 3.30 vs 48.05 +/- 3. 56 for invasion and 35.35 +/- 3.03 vs 52.45 +/- 1.04 for
      motility (all P < 0.01). CONCLUSION: Puerarin can inhibit the adhesion, invasion
      and migration of HO-8910 cells, plays an antagonist effect against the
      stimulation of estrogen on the malignant behavior of tumor cells.

PMID- 19852299
TI  - [Dynamical distribution of bone marrow mesenchymal stem cells in rat model of
      chronic aristolochic acid nephropathy].
AB  - OBJECTIVE: To investigate the distributive path and proliferative rule of marrow
      mesenchymal stem cells (MSCs) in the rat transplanted via caudal vein from male
      rat to female rats model of chronic aristolochic acid nephropathy (CAAN).
      METHODS: Cells taken from femoral bone marrow of male Wistar rats were made into
      single cell suspension, cultured, purified and identified as MSCs. MSCs were
      transplanted via caudal vein into 50 female Wistar CAAN model rats allocated in
      the test group, they were killed, 10 rats in a batch, at various time points (6
      h, 48 h, 10 d, 30 d and 60 d after transplantation). Besides, 10 rats allocated
      in the control group were killed on the 30th day after received sham
      transplantation. Kidney tissue of all rats was taken for detecting cells
      originated from the donors by fluorescence in situ hybridization test with FAM
      labeled sex determining region of Y chromosome (SRY FISH) probe, and their number
      in SRY was counted using SRY PCR. RESULTS: MSCs were mainly distributed in the
      glomerular capillaries at the time points of 6 h and 48 h, but the number of MSCs
      in glomerular capillaries decreased and those in renal mesenchyma increased at
      the time points from 10 d to 60 d gradually, then tended to a steady state,
      meanwhile it showed a stable increasing trend in renal tubule. Cell colony of
      MSCs could be found in mesenchyma with a slowed down increasing between 30 d to
      60 d, but the increasing in tubule was still steady. CONCLUSION: MSCs originated
      from the donor can enter the kidney of acceptor and distribute from blood
      capillary to renal mesenchyma and tubule, and they can long time inhabit there
      and make propagation.

PMID- 19852301
TI  - [Study on the objectivity of traditional Chinese medicinal tongue inspection].
AB  - The traditional Chinese medicinal (TCM) inspection on tongue features are always
      observed with naked eye, and the syndrome is differentiated depended only on
      experience. These disadvantages cannot but badly impact not only the inheritance
      but also the advance and development of TCM. Hence, to bring out the
      standardization and objectivity of TCM tongue inspection is a task urgently
      expected. Along with the advancing of modernized TCM research, to study the
      tongue feature with modern scientific and technologic approaches for making it
      more quantitative, objective and standardized becomes the main research
      orientations of tongue inspection. Taking computerized automatic reorganization
      of tongue feature as a main clue, the techniques involving collection, resolution
      and signature analysis of tongue feature were discussed in this paper.

PMID- 19852300
TI  - [Protective effect of Pogostemon cablin on membrane fluidity of intestinal
      epithelia cell in ischemia/ reperfusion rats after ischemia/reperfusion].
AB  - OBJECTIVE: To observe the effects of Pogostemon cablin (Blanco) Benth. (PCB), a
      Chinese aromatic herbal medicine, on serum levels of nitric oxide (NO), tumor
      necrosis factor-alpha (TNF-alpha), and membrane fluidity of intestinal epithelial
      cells (IMC) in rats undergoing lower limbs ischemic reperfusion (I/R), for
      exploring its action in protecting intestinal barrier and the possible
      mechanisms, and to seek a new way, viewing from Chinese medicine, for providing
      the experimental bases of gastrointestinal protection against trauma or surgical
      operation. METHODS: Eighty adult Wistar rats were induced into lower limb I/R
      model and randomized equally into the model group, the three PCB water extract
      groups treated respectively with high- (4 g x kg(-1) x d(-10), middle- (3 g x kg(
      1) x d(-1)), and low-dose (2 g x kg(-1) x d(-1)) of PCB water extract, and three
      PCB volatile oil groups treated respectively with high- (4 g x kg(-1) x d(-1)),
      middle- (3 g x kg(-1) x d(-1)), low-dose (2 g x kg(-1) d(-1) of PCB volatile oil.
      Besides, 10 healthy rats was allocated in a normal control group. PCB preparation
      was given via gastric infusion for 5 successive days just before modeling. The
      serum levels of NO and TNF-alpha were monitored, and the membranous fluidity of
      IMC at I/R region was determined by fluorescence polarization technique. RESULTS:
      Compared with the control group, both serum NO and TNF-alpha levels in model rats
      were significantly higher (P < 0.01), and the fluorescence polarization value (P)
      of IMC obviously increased at the same time (P < 0.05). As compared with the
      model group, the serum level of NO and TNF-alpha significantly reduced in all the
      PCB treated groups (P < 0.01 or P < 0.05). As for the membrane fluidity,
      significant difference was shown between the model group with low-dose of PCB
      water extract and middle-dose of PCB volatile oil (P < 0.05). CONCLUSION: PCB
      could effectively protect the intestinal barrier function by way of maintaining
      the membrane fluidity of IMC through regulating the level of NO and TNF-alpha in
      serum.

PMID- 19852302
TI  - [Observation on therapeutic effect of runmushu oral liquid in treating
      xerophthalmia in postmenopausal women].
AB  - OBJECTIVE: To objectively evaluate the therapeutic effect and safety of Runmushu
      Oral Liquid (RMS) for the treatment of xerophthalmia in postmenopausal women.
      METHODS: Seventy-two postmenopausal women (144 eyes) with xerophthalmia of
      aqueous tear deficiency type were assigned to two groups. Patients in the treated
      group were treated with RMS (consisted of prepared and crude rehmannia root,
      figwort, lilyturf root, dendrobium stem, wolfberry fruit, chrysanthemum and
      sticktight) orally combining with local applying of Hialid eye drops; while those
      in the control group were treated with Hialid eye drops alone. Changes of
      subjective symptoms and objective indices in the two groups were observed and
      compared before and after 1-month treatment. RESULTS: After 1 month of treatment,
      the total effective rate was 86.1% (62/72) in the treated group and 66.7% (48/72)
      in the control group, showing significant difference between them (P < 0.01).
      Significant differences between groups were also shown in improvements of total
      scores of subjective symptoms (P < 0.01), scores of tear film break-up time (BUT)
      and Schirmer I test, these indices in the treated group were better (P < 0.01).
      However, the improvement of cornea fluorescin staining scores was insignificant
      different between groups (P > 0.05). CONCLUSION: RMS with artificial-tears can
      alleviate the eye symptoms, prolong the BUT, promote the secretion of tears in
      treating postmenopausal women xerophthalmia, showing a therapeutic effect
      superior to that by artificial-tears alone.

PMID- 19852303
TI  - [Clinical observation on treatment of 10 patients with chronic inflammatory
      demyelinating polyneuropathy by gullong tongluo capsule combined with
      prednisone].
AB  - OBJECTIVE: To observe and evaluate objectively the clinical effect of Guilong
      Tongluo Capsule (GTC) in treating chronic inflammatory demyelinating
      polyneuropathy (CIDP). METHODS: Sixty CIDP patients were equally randomized into
      two groups. The treated group was administered with GTC and prednisone, while the
      control group with prednisone alone. Changes before and after 3-month treatment
      in terms of muscle force, functional and sensory disturbance of extremities, as
      well as scoring by Activity of Daily Living Scale (ADL) and electromyogram (EMG)
      for nerve conduction velocity were observed and compared. RESULTS: The total
      effective rate gained in the treated group and the control group was 90.0%
      (27/30) and 70.0% (21/30) respectively, showing significant difference between
      them (chi2 = 14.82, P < 0.01). The improvement in the treated group was superior
      to the control group in muscle force of lower limb, motive and sensory function
      of extremities, ADL scores and motive function of ulnar nerve (P < 0.05, P <
      0.01). CONCLUSION: The curative effect of GTC combined with prednisone in
      treating CIDP was better than that of prednisone alone.

PMID- 19852304
TI  - [The design, implementation, supervision and reporting of multi-centered
      acupunctural clinical trial].
AB  - In order to ensure and enhance the level and quality of acupunctural clinical
      trial, the design, implementation, supervision and reporting of multi-centered
      acupunctural clinical trial, its concrete methods and main significance, were
      introduced in this paper by taking the Major State Basic Research Development
      Program of China("973 Program") and "11th Five-Year Plan Period" National Key
      Technology Research and Development Program of China supported items for
      illustration. Besides that attention should be paid to randomization, controlling
      and blinded methods, the power and the sample size calculation as well as the
      medical ethics are also important in design. The registration of clinical trials,
      formulation of the standard operation procedures and training of researchers are
      the key points in the implementing process. And the emphases in supervision are
      the establishment and execution of a supervising system, which are the important
      links for ensuring the quality of research. In addition, the reporting of
      acupunctural clinical trials should follow the CONSORT (Consolidated Standards
      for Reporting Trials) statement and the STRICTA (Standards for Reporting
      Interventions in Controlled Trials of Acupuncture) recommendations.

PMID- 19852305
TI  - [Exploration into the preparation of placebos used in Chinese medicinal clinical
      trial].
AB  - Placebo-controlled clinical trials have been more and more emphasized in
      traditional Chinese medicine (TCM) researches, while the preparation of TCM
      placebos is still to be improved. For this work, some elements should be taken
      into consideration comprehensively, including the design of clinical trial, the
      characteristics of researched disease, the nature of testing drugs, and the way
      of medication, etc. And the technological process for placebo manufacturing
      should be selected properly depending upon the basis of the above elements. Un
      biased foodstuff is good as excipient for TCM placebos preparation. The placebo
      should be made in dosage-form similar to that of the testing drug as possible, if
      there are difficulties for simulating them in appearance and smell completely.
      However, its potential pharmacological activity meeting to the acceptance of
      researchers should be ensured.

PMID- 19852306
TI  - [Progress of research in respect of improving uterine membranous receptivity by
      Chinese drugs].

PMID- 19852307
TI  - Occluding the round window causes no change in threshold, but an increase in
      hearing loss following noise exposure.
AB  - AIM: To assess the effects of occluding the round window on the degree of hearing
      loss following exposure to broad band noise. DESIGN: Following opening of the
      middle ear bulla in both ears of ten sand rats, auditory nerve-brainstem evoked
      response (ABR) thresholds were determined in each ear separately using an insert
      earphone. The round window of one ear was then occluded with super-glue. The
      opposite ear was sham-operated. ABR thresholds were again assessed immediately.
      The animals were then exposed to 113 dB SPL broad band noise for 12 hours. 24
      hours after the round window was occluded, which was 8-10 hours after the end of
      the noise exposure, ABR thresholds were again determined in each ear. In four
      control animals, the round window was blocked, but they were not exposed to
      noise. RESULTS: Following the noise exposure, the mean ABR threshold elevation in
      the round window blocked ears (54.5 +/- 5.5 dB) was significantly (p < 0.004)
      greater than that in the sham-operated ear (40.5 +/- 8.6 dB). In the four control
      ears, there was no change in ABR threshold 24 hours after the round window was
      occluded. CONCLUSION: Occluding the round window was not accompanied by a
      threshold elevation, but following noise exposure, the noise induced hearing loss
      was increased, probably by reducing the efficacy of an inherent protective
      mechanical mechanism.

PMID- 19852308
TI  - Central auditory processing development in adolescents with and without learning
      disabilities.
AB  - Auditory processing deficit (APD) is estimated to affect 5% of school-age
      children and adolescents, and 30-50% of those diagnosed with learning problems.
      The diagnosis and indeed the existence of APD, however, remain controversial. One
      reason for this controversy is that the factors contributing to normal variations
      in auditory processing and its development are poorly understood. To address the
      developmental issue, we compared the performance of younger (14 yr/o) and older
      (18 yr/o) adolescents on frequency discrimination, backward masking detection and
      gap detection using an oddball paradigm. Older adolescents had lower backward
      masking thresholds compared with younger adolescents, but the prolonged
      development of thresholds was not accompanied by a corresponding increase in
      performance consistency. The distribution of thresholds on all three tasks did
      not differ between typically developing adolescents and those diagnosed with
      learning disabilities. A questionnaire designed to tap difficulties in daily
      listening situations also failed to differentiate the two groups. These findings
      suggest that basing the diagnosis of APD on tests conducted with the oddball
      procedure requires the establishment of norms from large and age specific
      samples. They also suggest that the development of auditory sensory acuity in the
      general population is longer than typically assumed.

PMID- 19852309
TI  - Are changes in pitch and formants enough to influence talker normalization
      processes in children and adults?
AB  - In the present study, we examined the influence of mean F0 and formant values on
      talker normalization. Initially, two speakers recorded an identical set of 10
      isophonemic word lists in Hebrew, consisting of 10 words each. These recordings
      were then manipulated by means that affect F0 only, or both F0 and formant
      frequencies. Different degrees of manipulation were carried out in order to
      create a new set of lists which were perceived to have been obtained from
      multiple talkers. The original and manipulated lists were presented to a group of
      12 adults and 12 children at 30 dB above pure-tone average thresholds (PTA). Half
      of the listeners was presented with the single-talker lists first and then the
      multiple-talker lists, and the other half was presented with the word lists in
      reversed order. Listeners were instructed to repeat the words they heard. Correct
      word recognition was scored. The results indicated: (1) lower word recognition
      scores for the multiple-talker lists than for the single-talker lists, for both
      children and adults, (2) larger inter-subject variability in performance for the
      multiple-talker compared to the single-talker lists for both age groups, and (3)
      that order of presentation influenced word recognition of the multiple-talker
      lists only, being worse when presented first. Our findings support the following:
      (1) manipulations of F0 and formants of a single talker are sufficient to
      influence talker normalization processes, (2) this influence varies between
      listeners suggesting that listeners do not use the same acoustic information in
      their speech perception process, and (3) even adults, who are proficient in the
      language, do not eliminate entirely the irrelevant talker-specific acoustic
      information in the speech perception process.

PMID- 19852310
TI  - Wavelet analysis of the frontal auditory evoked potentials obtained in the
      passive oddball paradigm in healthy subjects and schizophrenics.
AB  - The goal of the present study was to apply the oscillatory brain dynamics model
      to the structural and quantitative analysis of neurocognitive functions
      considered as a potential marker of schizophrenia. This was achieved in tests of
      the detection of auditory events deviating in the regular auditory stream
      (oddball paradigm, MMN effect). It was hypothesized that the post-stimulus peaks
      of the oscillation power localized in post-stimulus time in the definite EEG
      oscillators represented neuro-electrical 'events' evoked in the specific neuronal
      nets characterized by this oscillation frequency band. We suggest that the time
      frequency destination of these events related to the activation of the functional
      neuronal nets could be used for the determination of specific neurocognitive
      functions. Thus it was an attempt to distinguish the different neuro-functional
      parts of auditory processing and to compare these results between healthy
      subjects and patients with schizophrenia. The present results demonstrate the
      significant difference between the frontal averaged EEG oscillatory dynamics in
      healthy subjects and patients with schizophrenia related to neurocognitive
      function marked by the MMN and orienting response N200/P300a.

PMID- 19852311
TI  - [Two cases of cerebral sparganosis].

PMID- 19852312
TI  - Neonatal tetanus in Malaysia.

PMID- 19852313
TI  - Selecting antihypertensive medication in patients with essential hypertension in
      Malaysia.

PMID- 19852314
TI  - Comparing extracorporeal shock wave lithotripsy and ureteroscopy for treatment of
      proximal ureteric calculi: a cost-effectiveness study.
AB  - Extracorporeal shockwave lithotripsy (ESWL) and ureteroscopy (URS) are two main
      methods of treating proximal ureteric stones. Success rates and cost
      effectiveness of the two methods were compared. A total of 67 patients who
      underwent treatment between January 2007 and July 2007 at a state general
      hospital were included in the study. The success rate for ESWL group was 81.8%
      and for URS group was 84.6%. ESWL technique produced a significant higher overall
      cost per patient than URS (RM930.02 versus RM621.95 respectively). There was no
      significant difference in quality of patient's life. Cost-effectiveness ratio was
      lower for URS. The analysis suggested that URS was more cost-effective than ESWL.

PMID- 19852315
TI  - Is the femoral neck geometry adequate for placement of the proximal femoral nail
      in the Malaysian population? A review of 100 cases.
AB  - Issues that had been encountered during proximal femoral fracture fixation using
      proximal femoral nail include (i) the adequacy of the femoral neck width in the
      local population and (ii) the potential difficulty encountered during fixation in
      certain prefixed angles as determined by the implant. This was a retrospective,
      descriptive study evaluating the anterior-posterior pelvic radiographs of 100
      consecutive patients, from January to August 2007, managed at University Malaya
      Medical Centre, Kuala Lumpur. The femoral neck width in the population studied
      was adequate for placement of femoral neck screw and anti-rotation pin or hip pin
      using the proximal femoral nail implant. (mean = 34.0 +/- 3.7 mm, min = 24.6 mm).
      There was no significant difference between the working area using an implant
      angled at 130 degrees or 135 degrees (P = 0.91). Both femoral neck width and neck
      shaft angle of the Malaysian population studied were not a factor influencing the
      placement of femoral neck lag screws and anti-rotation pin.

PMID- 19852316
TI  - Pahang melioidosis registry.
AB  - Melioidosis has a high annual incidence and mortality rate in Pahang, Malaysia.
      We initiated the first melioidosis registry in the country on 1st July 2005 to
      improve the management of melioidosis in the state. Continuous medical education
      on melioidosis was carried out in all hospitals in the state to highlight the
      magnitude of the disease and to educate the doctors on the treatment of the
      disease. All culture confirmed cases were registered and analysed. During the one
      year study period from 1st July 2005 till 30th June 2006, a total of 63 patients
      had positive culture for Burkholderia pseudomallei. The calculated annual
      incidence of melioidosis in Pahang state was 4.3 per 100,000 population per year
      (Adult, 6.0 per 100, 000 population per year and paediatric, 1.6 per 100,000
      population per year). There were 55 Malays (87.3%), three Chinese (4.8%), four
      aborigines (6.3%) and one Indonesian. Nine (14.3%) were less than 18 years old.
      The median age was 49 years (range: 1-68 years). Only one patient (1.6%) had a
      previous history of confirmed melioidosis. With this programme, we had observed a
      decline in adult mortality from 54% to 44%, although this was not statistically
      significant. However, culture-confirmed relapses had dropped from 19% to nil.
      Several measures need to be taken to decrease mortality from melioidosis in
      endemic countries.

PMID- 19852317
TI  - A review of parotid tumours and their management: a ten-year-experience.
AB  - To review the demographics, management and outcome of patients undergoing
      parotidectomy at a tertiary center. A total of 76 patients who underwent
      parotidectomies from January 1996 to December 2005 at the ORL department of our
      center were reviewed. All clinical, operative, postoperative, histology data were
      gathered and reviewed. Fine-needle aspiration cytology (FNAC) was diagnostic in
      90% of patients with a sensitivity of 76% and specificity of 96%. Twenty-one
      patients had malignant tumours and the rest had benign or inflammatory lesions.
      There were a total of 48 superficial and 28 total parotidectomies performed.
      Facial nerve palsy occurred in 30 (39%) patients with 4% permanent palsy and 35%
      temporary palsy. The recurrence rate of pleomorphic adenoma was 2.6%. FNAC and CT
      scan were performed prior to the surgery were useful guidance in planning the
      operation but clinical judgment is more important. The most common surgery
      performed was superficial parotidectomy and the most common cause was due to
      pleomorphic adenoma. The incidence of complications and recurrence of tumour are
      comparable to other international studies. Prior knowledge of anatomy and careful
      planning is needed to decrease the incidence of facial nerve palsy.

PMID- 19852318
TI  - Acute stroke patients with high BMI are less likely to have severe disability at
      initial presentation.
AB  - This is a prospective study to determine the severity of disability and prognosis
      of acute stroke patients related to their Body Mass index (BMI). A total of 79
      consecutive CT-scan-proven acute stroke patients who were admitted to Hospital
      Tuanku Ja'afar, Seremban between November 2006 and April 2007 were recruited
      (male:female 49:30; mean age 62.7 years; ischemic stroke 70, intracerebral bleed
      9). The patients were divided according to BMI less than 25 (Group A) and equal
      or greater than 25 (Group B). Severity of disability was measured between 24-48
      hours by modified Rankin's score. Patients were followed up after one month.
      Thirty-seven patients had severe disability (Rankin Score 5). Twenty-nine
      patients had adverse outcomes including 11 deaths and 18 rehospitalizations or
      prolonged hospital/nursing home stay. 34.3% of Group B had severe disability
      compared to 56.8% of Group A (chi2 P = 0.046). Conversely 42.9% of Group B had
      adverse events at one month compared to 31.8% of Group A (chi2 P = 0.312). There
      were no statistical differences between high- and low-BMI groups for gender
      ratio, smoking, hypertension, diabetes, prior cardiovascular disease, mean age,
      mean lipid profile and blood pressure. When comparing patients with Rankin Score
      1-4 versus 5, age and BMI were statistically significant between the two groups.
      By multivariate analysis only age is independent predictor for severe disability
      (P < 0.05). The results of this pilot study should be confirmed in larger
      prospective multicentre trial.

PMID- 19852319
TI  - Isolation of measles virus from clinical specimens using B95a and Vero/hSLAM cell
      lines.
AB  - The clinical presentation of acute measles is normally quite typical, especially
      in the presence of Koplik's spots, that laboratory test is seldom required to
      confirm the diagnosis. However, with wide measles vaccination coverage and the
      extensive use of immunosuppressive chemotherapy, the diagnosis of atypical
      manifestations of acute measles may require laboratory confirmation. When
      compared with B95a cell-line, this study shows that the Vero/hSLAM cell-line is
      sensitive and is recommended for use in the primary isolation of wild-type
      measles virus from clinical specimens. Throat swab and urine specimens are the
      clinical specimens of choice and both are recommended for optimal isolation of
      measles virus from patients suspected of acute measles virus infection.

PMID- 19852320
TI  - Awareness and knowledge on eye donation among university students.
AB  - Four hundred (400) students studying first year Medicine, Dentistry, Laboratory
      Technology, Pharmacy, Biomedicine and Bioengineering degree courses in the
      University of Malaya were assessed on their awareness and knowledge on eye
      donation using an open ended questionnaire. The majority of the students (344,
      86%) in this study were aware about eye donation; the awareness was higher in
      biomedical (77.1%) and medical students (76.7%) compared to the others (55.9%
      70.7%). One hundred and eight students (27%) were willing to donate their eyes.
      Most of the students (376, 94%) did not know about any eye bank in Malaysia. One
      hundred and sixty (40%) students were aware that whole eye can be removed from
      the donor and 101 (25.25%) were aware that the cornea can be removed separately.
      However, only 121 (30.25%) knew that donated eyes were used for corneal grafting.
      More than half of the students (231, 57.7%) did not know that the donor eye could
      be stored before transplantation. The results of this study indicate that there
      is a need to educate the young adults in our society about corneal
      transplantation so that they can in turn motivate other members of society and
      their own family members to become eye donors, thus facilitating the availability
      of donor corneas for corneal transplantation in Malaysia.

PMID- 19852321
TI  - How should Malaysia respond to its ageing society?
AB  - As Malaysia ages its health and social care systems will have to adapt to a
      changing pattern of disease and dependency. Improved public health measures
      extend life expectancy at the relative expense of increased prevalence of
      currently incurable conditions such as dementia and Parkinson's disease. In this
      article we discuss how these demographic changes will impact and suggest possible
      means of coping with the altered epidemiology of disease and disability. Malaysia
      will need to swiftly develop sufficient expertise in acute Geriatric Medicine,
      rehabilitation of older people; the management of long-term conditions in older
      people with multiple complex problems within Primary Care; as well as an
      infrastructure for home and institutional care.

PMID- 19852322
TI  - Training future doctors to be patient-centred: efficacy of a communication skills
      training (CST) programme in a Malaysian medical institution.
AB  - This study evaluates the efficacy of the preclinical communication skills
      training (CST) programme at the International Medical University in Malaysia.
      Efficacy indicators include students' (1) perceived competency (2) attitude (3)
      conceptual knowledge, and (4) performance with regard to patient-centred
      communication. A longitudinal study with a before-after design tracked a
      preclinical cohort's progress on the aforementioned indicators as they advance
      through the training. Results indicate that following the CST, students perceived
      themselves to be more competent in interpersonal communication, had more positive
      attitude towards patient-centred communication, and developed a better conceptual
      knowledge of doctor-patient communication. In addition, those with good
      conceptual knowledge tend to demonstrate better communication skills performance
      at the Objective Structure Clinical Examination 12 months following the initial
      CST.

PMID- 19852323
TI  - Dizziness, a review of walk-in patients at a specialised neurotology clinic.
AB  - A retrospective review of 100 walk-in patients at a specialized neurotology
      clinic in dizziness at a tertiary referral centre is presented. The most common
      cause of dizziness was BPPV, forming 31% of the cases. Other causes in order of
      frequency include recurrent vestibulopathy, idiopathic causes, Meniere's disease
      and central causes.

PMID- 19852324
TI  - Routine histological examination for nasal polyp specimens: is it necessary?
AB  - Nasal polyp is one of the common causes of nasal obstruction. The diagnosis is
      usually made on clinical ground and rarely needs histological examination.
      However, when a candidate is selected for the surgical option of polyp removal,
      there is tendency to send all specimens for routine histological examination. The
      objective of this study was to assess the necessity of routinely performed
      histological examination in all nasal polyp specimens. A retrospective review of
      all nasal polyp histological reports was done from patients who underwent
      polypectomy or functional endoscopic sinus surgery in Universiti Sains Malaysia
      Hospital between January 2000 to July 2006. It consisted of 95 patients. Majority
      of the reports came back as inflammatory nasal polyp (93.6%) and other varieties
      of benign nasal mass (5.3%). However, one specimen was noted to be malignant
      (1.1%). In conclusion all nasal polyp specimens should be sent for histological
      examination in order to confirm the diagnosis.

PMID- 19852325
TI  - Candidaemia and antifungal susceptibility testing in a teaching hospital.
AB  - We reviewed cases of candidaemia at Universiti Kebangsaan Malaysia Medical Centre
      from 1st January 2005 to 30th June 2006. All blood cultures positive for Candida
      species or its teleomorphs within the study period were identified and antifungal
      susceptibility testing was performed. Out of 50 blood isolates, 20 (40%) were
      identified as Candida albicans, 16 (32%) C. tropicalis, five (10%) C.
      parapsilosis, three (6%) C. famata, two (4%) C. glabrata, two (4%) Pichia ohmeri,
      one (2%) C. krusei and one (2%) P. etchell/carsonii. Susceptibility to
      amphotericin B was 100%, fluconazole 90%, itraconazole 40%, ketoconazole 88%, 5
      flucytosine 98% and voriconazole 98%.

PMID- 19852326
TI  - Compliance towards methadone maintenance therapy and its associated factors in
      Selangor primary care centers and Kuala Lumpur hospital.
AB  - This paper seeks to determine the client's compliance level towards Methadone
      Maintenance Therapy (MMT) and identify its associated factors. A cross sectional
      study was conducted from June to September 2007 where 288 samples were
      interviewed. The outcomes were divided into good compliance and partial
      compliance categories. Overall client's compliance level is good at 86.1%. There
      are significant difference between mean age of groups (t = -2.041, p = 0.04); and
      significant associations of job's status (chi2 = 9.54, p = 0.008); client's
      confident score (t = -3.12, p = 0.023), client'ssocial function score (t = 
      2.308, p = 0.002) and client's social function level (chi2 = 5.43, p = 0.02) with
      compliance toward program. With multivariate analysis, only client's age,
      client's confidence score and client's job status were related to compliance
      status. It was concluded that there is high compliance rate among client's who
      received the program. Younger clients, low scores on client's confident and
      social function, and clients with unsteady jobs are at risk not to comply with
      treatment.

PMID- 19852327
TI  - Comparison of morphine with fentanyl added to intrathecal 0.5% hyperbaric
      bupivacaine for analgesia after caesarean section.
AB  - This was a prospective randomised, controlled, single-blind study done to
      determine the effect of intrathecal morphine 0.1 mg as compared with intrathecal
      fentanyl 25 microg in terms of analgesia and duration for postoperative pain
      relief after Caesarean section. Sixty ASA I or II parturients were randomised
      into two groups. Group 1 (n=33) received 1.8 ml of 0.5% hyperbaric bupivacaine
      combined with 0.1 mg morphine while Group 2 (n=27) received 1.8 ml of 0.5%
      hyperbaric bupivacaine combined with 25 microg fentanyl for spinal anaesthesia.
      Postoperatively, all patients were provided with patient controlled analgesia
      (PCA) morphine. Pain was assessed using visual analogue score (VAS) at 6, 12, 18
      and 24 hours. Time to first demand of PCA morphine, cumulative PCA morphine
      requirement and opioid side effects were documented. The VAS for pain and the
      cumulative PCA morphine requirement were both significantly lower in Group 1 (p <
      0.05) during the 24 hours study period. The time to first demand was also
      significantly longer in Group 1 (p < 0.05). Overall, there were no significant
      difference between the two groups in side effects, except for a high incidence of
      nausea and vomiting requiring treatment in Group B in the first six hours. In
      conclusion the addition of 0.1 mg morphine for spinal anaesthesia provided
      superior and longer postoperative analgesia after Caesarean section.

PMID- 19852328
TI  - Pleurovideoscopy in a general hospital.
AB  - A 48 a year old Malay gentleman, was investigated for recurrent unexplained right
      pleural effusion. Initial investigations showed exudative pleural effusion with
      neutrophil predominance. Tuberculosis (TB) workout were negative. Pleuroscopy
      showed multiple adhesions with granulomatous deposits at the parietal pleural
      surface. Adhesions were released by forceps. A chest tube was inserted.
      Intrapleural streptokinase instilled for three consecutive days. TB treatment was
      initiated. There was clinical and radiological improvement and he was discharged
      well after one week of hospitalization. He remained well at follow-up two months
      later.

PMID- 19852329
TI  - Domiciliary non-invasive ventilatory devices--a general hospital experience.
AB  - Treatment for chronic respiratory failure has advanced since the introduction of
      domiciliary non-invasive ventilatory devices. This has given a new light of hope
      for patients with chronic respiratory failure secondary to various causes. We
      report a series of patients with respiratory failure of different origins and
      types of management that they received. Four patients received bilevel positive
      airway pressure (BiPAP) and one patient received continuous positive airway
      pressure (CPAP).

PMID- 19852330
TI  - Neonatal tetanus: a study of five cases in Sandakan, Sabah.
AB  - This study aims to study the demographics, clinical presentation, treatment and
      outcome of neonatal tetanus patients managed at Hospital Duchess of Kent from
      January 1st 2006 to December 31st 2006. Five neonates were studied. All presented
      with fever, poor sucking and limb stiffness, with a history of unsterile delivery
      and uncertain maternal tetanus immunity status. All were nursed in a minimal
      stimuli environment and were given IV penicillin G, IM tetanus immunoglobulin and
      sedatives to control spasms. Nutrition and chest physiotherapy were rendered.
      Three patients required artificial ventilation. Duration of treatment ranged from
      25 to 44 days. All survived. Inadequate maternal immunization, unsterile delivery
      and inappropriate umbilical cord care are major contributing factors of neonatal
      tetanus in our study. Supportive measures are the mainstay of treatment in our
      setting with very limited resources.

PMID- 19852331
TI  - A case of neonatal diarrhoea caused by congenital glucose-galactose
      malabsorption.
AB  - A five-month-old Indian girl, product of consanguineous marriage, presented with
      diarrhoea with an onset within two days after birth, severe malnutrition and
      metabolic acidosis. The diarrhoea persisted even with lactose-free formula, amino
      acid-based formula and glucose-containing oral rehydration solution, but stopped
      when fasted. She required prolonged parenteral nutrition. Fructose and glucose
      tolerance tests were performed, confirming the child was able to absorb and
      metabolize fructose but not glucose, indicating a diagnosis of glucose-galactose
      malabsorption. This case illustrate how simple and pertinent clinical
      observations and laboratory investigations is sufficient to allow a firm
      diagnosis to be made.

PMID- 19852332
TI  - Disseminated Penicilium marneffei infection.
AB  - This is a case report of disseminated Penicillium marneffei infection in a
      patient with leprosy, responding to antifungal therapy. Radiologically there were
      nodules in the left lung, right pleural effusion, lymphadenopathy in neck,
      mediastinum and upper abdomen and abscesses in the liver and right parietal lobe.
      This case highlights a rare infection in a non-HIV related immunocompromised
      patient, and its nonspecific radiologic manifestations.

PMID- 19852333
TI  - Unilateral adductor vocal cord palsy treated with the titanium vocal fold
      medializing implant (TVFMI).
AB  - Vocal cord palsy secondary to recurrent laryngeal nerve injury may be
      attributable to trauma, infiltrating neoplasm, congenital cardiac anomaly and
      others. Regardless the causes, majority of unilateral adductor palsy cases are
      usually managed by speech rehabilitation in order to allow compensation. In
      selected cases, medialization procedure may be required to achieve a complete
      glottal closure during phonation. Multiple techniques have been developed to
      achieve this goal. This case report illustrates the recent advancement in vocal
      fold medialization procedure, which has not been widely practiced in Malaysia.

PMID- 19852334
TI  - Malays in peninsular Malaysia may have the lowest incidence of stomach cancer in
      the world.
AB  - The Malaysian National Cancer Registry (NCR) report for the period 2003-2005
      shows an incidence of stomach cancer of 2.2 for Malay, 11.3 for Chinese and 11.9
      for Indian males per 100,000 population. Malay (1.3), Chinese (7.2) and Indian
      (7.2) women have rates lower than men. Malays in Peninsular Malaysia have five
      times less stomach cancer than Chinese and Indians. This racial difference is
      more marked than that noted in the Singapore cancer registry. Regional data from
      Kelantan has an even lower rate for Malays there (1.5 for males and 0.9 for
      females per 100,000 population). The incidence of Helicobacter pylori infection,
      a known risk factor for stomach cancer, is low among Malays.

PMID- 19852335
TI  - The A-B-C of haematopoietic stem cell transplantation.
AB  - Haematopoietic stem cell transplantation (HSCT) has progressed rapidly since its
      introduction about five decades ago. There is now an increasing demand for
      transplant physicians in both public and private domains to perform this
      procedure in view of significant improvement of remission rates in haematological
      malignancies and increasing indications of HSCT. Peripheral blood has largely
      replaced bone marrow as the preferred source of haematopoietic stem cells (HSC).
      Transplantation-related mortality and morbidity rates have considerably decreased
      because of improved conditioning regimens, human leukocyte antigen (HLA) typing
      methods, supportive care, and most importantly, prophylaxis, diagnosis and
      treatment of serious infections. New transplantation strategies, such as reduced
      intensity transplantation, have extended the use of allogeneic transplant to
      patients with older age and co-morbidities. Current efforts are focused on ways
      to increase the donor pool and to improve the long term outcome of HSCT survivors
      in particular to reduce the relapse rate and the late effects of HSCT. This
      article summarizes the sources and procurement of HSC, the types and process of
      HSCT, indications for HSCT and complications associated with HSCT with particular
      reference to the current practice within the local settings.

PMID- 19852336
TI  - Pre-eclampsia: a foetal view.

PMID- 19852337
TI  - Does elective re-siting of intravenous cannulae decrease peripheral
      thrombophlebitis? A randomized controlled study.
AB  - BACKGROUND: Peripheral venous thrombophlebitis (PVT) is a common complication of
      intravenous cannulation, occurring in about 30% of patients. We evaluated the
      effect of elective re-siting of intravenous cannulae every 48 hours on the
      incidence and severity of PVT in patients receiving intravenous fluids/drugs.
      METHODS: We randomized 42 patients who were admitted for major abdominal surgery
      to either the control or study group (n = 21 in either group). Informed consent
      was obtained from all of them. Cannulae in the control group were removed only if
      the site became painful, the cannula got dislodged or there were signs and
      symptoms suggestive of PVT, namely pain, erythema, swelling, excessive warmth or
      a palpable venous cord. Cannulae in the study group were changed and re-sited
      electively every 48 hours. All the patients were examined every 24 hours for
      signs and symptoms of PVT at the current and previous sites of infusion. RESULTS:
      The incidence of PVT was 100% (21/21) in the control group and only 9.5% (2/21)
      in the study group (p < 0.0001). The severity of PVT was also less in the study
      group compared with that in the control group. Day-wise correlation of the
      incidence of PVT showed that 82.6% of the episodes of PVT occurred on day 3.
      CONCLUSION: Elective re-siting of intravenous cannulae every 48 hours results in
      a significant reduction in the incidence and severity of PVT. We recommend that
      this should be adopted as standard practice in managing all patients who require
      prolonged intravenous therapy.

PMID- 19852338
TI  - Short-term heart rate variability measures in students during examinations.
AB  - BACKGROUND: Heart rate variability measures are reported to be altered in
      patients with various diseases, implying related abnormality of cardiac autonomic
      function. Could associated anxiety-induced mental stress, invariably present in
      all patients, contribute to these alterations? To address this question, we
      compared heart rate variability parameters computed from students during
      university examinations, a known cause of mental stress, with those computed
      during holidays when students are mentally relaxed. We felt that the changes in
      heart rate variability, if any, could be attributed to mental stress alone.
      METHODS: We compared short-term heart rate variability parameters computed from 5
      minute electrocardiogram recordings during supine rest in 18 healthy students,
      along with recordings of respiratory rate and blood pressure, during university
      examinations and holidays. RESULTS: The mean of all the RR intervals was
      significantly lower, while the mean arterial pressure was significantly higher at
      the time of examinations. Measures of total variability, namely standard
      deviation of the normal-to-normal RR intervals and total spectral power, were
      significantly reduced during examinations. Low frequency normalized units (LF
      nu), high frequency (HF) nu and the LF/HF ratio were not significantly different.
      CONCLUSION: The decreased mean RR interval indicates an overall increase in heart
      rate or cardiac sympatho-excitation during examinations. This is associated with
      a decrease in total heart rate variability at the time of mental stress. None of
      the parameters indicative of the ratio of the extent of modulation of cardiac
      sympathetic to parasympathetic activity were different. These findings may be
      useful when interpreting measures of heart rate variability in patients.

PMID- 19852339
TI  - Modified, weekly dosing with docetaxel and cisplatin as first-line therapy in
      advanced non-small cell lung cancer.
AB  - BACKGROUND: Platinum-based combination chemotherapy regimens provide modest
      improvement in both survival and quality of life for patients with non-small cell
      lung cancers and docetaxel is the first agent approved for both first- and second
      line treatment in patients with advanced disease. However, the regimens are
      associated with adverse effects. METHODS: We used a modified, shortened regimen
      with only 2 consecutive weekly infusions of docetaxel followed by rest for 1
      week, and evaluated the efficacy and toxicity profiles in patients undergoing
      treatment for non-small cell lung cancers. Thirty-five patients (19 men, 16
      women) with advanced non-small cell lung cancers received docetaxel (35 mg/m2
      i.v. infusion on days 1 and 8) with cisplatin (60 mg/m2 i.v. infusion on day 8)
      in 126 cycles. RESULTS: Two of the 35 patients achieved complete response (5.7%),
      while 16 patients achieved partial response (45.7%). The overall response rate
      was 51.4% and median overall survival was 10.6 months. The toxicities were mild;
      the most common grades 3 and 4 toxicities were anaemia (5.6%), neutropenia (4.8%)
      and vomiting (5.6%). Other grades 3 and 4 non-haematological toxicities included
      diarrhoea (3.2%), neurotoxicity (0.8%), asthenia (0.8%) and phlebitis (0.8%).
      CONCLUSION: Combination chemotherapy with cisplatin and 2 consecutive weekly
      infusions of docetaxel can be considered an active and well-tolerated regimen
      with a good response rate and less toxicity for patients with advanced non-small
      cell lung cancers.

PMID- 19852340
TI  - Laryngeal stridor and myocardial infarction in a renal transplant recipient.
AB  - A living-unrelated renal transplant recipient presented with a history of fever
      with chills and rigors for 3 days. Clinically, the cause of the fever could not
      be localized. During a hospital stay of 72 hours, the patient developed sore
      throat, laryngeal stridor and acute myocardial infarction. A post-mortem revealed
      disseminated mucormycosis involving the larynx, heart, intestines, brain and the
      transplanted kidney.

PMID- 19852341
TI  - Prevalence of rheumatic heart disease: has it declined in India?
AB  - Rheumatic heart disease continues to be a major health problem in many parts of
      the world. The epidemiology of rheumatic heart disease in India is of special
      interest as it may help to understand the effects of economic transition on this
      enigmatic disease. Critical appraisal of the published literature suggests the
      possibility of a real decline in the occurrence of the disease in some parts of
      the country, but a continuing onslaught in several other regions. The rate of
      decline seems to correlate more with improved public health facilities than with
      economic development alone. However, the cumulative burden of the disease remains
      high, and sustained efforts for the prevention of rheumatic heart disease are
      warranted.

PMID- 19852342
TI  - Lymphocytosis and chronic leukaemia.

PMID- 19852344
TI  - Coronary artery bypass or percutaneous intervention for multivessel coronary
      artery disease.

PMID- 19852343
TI  - The role of mechanical bowel preparation before colorectal surgery.

PMID- 19852345
TI  - Deafness: burden, prevention and control in India.
AB  - The high burden of deafness globally and in India is largely preventable and
      avoidable. According to the 2005 estimates of WHO, 278 million people have
      disabling hearing impairment. The prevalence of deafness in Southeast Asia ranges
      from 4.6% to 8.8%. In India, 63 million people (6.3%) suffer from significant
      auditory loss. Nationwide disability surveys have estimated hearing loss to be
      the second most common cause of disability. A lack of skilled manpower and human
      resources make this problem a huge challenge. The Government of India has
      launched the National Programme for Prevention and Control of Deafness. This
      article highlights the major components of the programme with a focus on manpower
      development and ear service provision including rehabilitation. Since the
      programme is also being implemented at the primary healthcare level, it envisages
      a reduction in the burden of deafness and prevention of future hearing loss in
      India.

PMID- 19852346
TI  - Internal assessment revisited.

PMID- 19852347
TI  - Prakash and Mandakini Amte. Interview by Prabha Desikan.

PMID- 19852348
TI  - Science and stimulus.

PMID- 19852349
TI  - AIDS at the margin: experiences and lessons from marginalized groups in India
      (Part I).

PMID- 19852351
TI  - Adventure sports events in India need better medical preparedness.

PMID- 19852350
TI  - Medical students' awareness and motivation for research.

PMID- 19852352
TI  - Oseltamivir (Tamiflu) for pandemic influenza in India: some issues.

PMID- 19852353
TI  - [Urinary infestation of Tarsonemus mites complicated with hematuria in three
      males].

PMID- 19852354
TI  - [Enhancing protective immunity effects of TPI DNA vaccine against Schistosoma
      japonicum through codon optimization].
AB  - OBJECTIVE: To study the protective effect of codon optimized TPI DNA vaccine
      against Schistosoma japonicum infection. METHODS: Sixty female BALB/c mice were
      randomly divided into 5 groups. The mice were injected through musculus
      quadriceps femoris with 100 microg pcDNA 3.1 control (Group A), pcDNA3.1-TPI
      (Group B), pcDNA 3.1-TPI-mHSP70 (Group C), pcDNA3.1-TPI.opt (Group D), and
      pcDNA3.1-TPI.opt-mHSP70 (Group E) respectively. All mice were immunized for three
      times with an interval of two weeks. The mice were challenged with (40+/-1)
      cercariae of S. japonicum per mouse by abdominal skin penetration 4 weeks after
      the last immunization, and sacrificed at 42 days post-challenge, the number of
      worms or hepatic eggs was counted. Blood was taken for the detection of IgG,
      IgG1, and IgG2a 2 days before immunization and before challenge, respectively.
      Spleen cells of 2 mice from each group were cultured and stimulated with ConA and
      rSjCTPI peptide, and the supernatant was collected for detection of IL-2, IL-4,
      IL-5, IFN-gamma, and TNF by flow cytometry. RESULTS: ELISA showed that the mice
      in groups B, C, D, and E produced specific IgG and IgG1, IgG2a antibody isotypes,
      and the ratio of IgG2a/IgG1 was 1.73, 2.06, 2.44, and 3.09, respectively. The
      levels of IL-2, IFN-gamma and TNF in groups D and E were higher than that of
      groups B and C. The worm reduction rate and hepatic egg reduction rate in groups
      D (36.03%, 41.7%) and E (39.03%, 46.85%) were higher than those of groups B
      (26.28%, 28.35%) and C (28.38%, 31.39%) (P<0.01) . CONCLUSIONS: The codon
      optimized TPI DNA vaccine induces higher level of protective effect and Th1
      biased cellular immune response than those of non-optimized TPI DNA vaccine.

PMID- 19852355
TI  - [An imported case of falciparum malaria in Cixi City].

PMID- 19852356
TI  - [Cloning, expression and immunogenicity analysis of cathepsin L-like protease of
      Fasciola hepatica].
AB  - OBJECTIVE: To clone and express the cathepsin L-like protease gene of Fasciola
      hepatica (FhCL) and investigate the immunogenicity of the recombinant FhCL
      protein. METHODS: Specific primers were designed according to the reported FhCL
      gene in GenBank. Using total RNA from adult worms of F. hepatica, FhCL gene was
      amplified by RT-PCR. The PCR product was cloned into pMD18-T vector and then
      subcloned into pET30a(+) vector. The recombinant plasmid was transformed into E.
      coli BL21 (DE3) and followed by expression of the protein induced by IPTG. The
      expression situation of recombinant FhCL was analyzed by SDS-PAGE. Its
      immunoresponse to the sera of infected goat and the antisera of SD rats against
      FhCL was examined by Western blotting analysis. RESULTS: PCR and double enzyme
      digestion showed that the FhCL gene fragment was about 1,000 bp in length. The
      constructed recombinant plasmid pET30a (+)-FhCL was identified by sequencing. The
      recombinant protein (Mr 42,000) was expressed in the form of inclusion body. The
      protein was recognized respectively by the sera of infected goat and the sera
      from rat immunized with FhCL. CONCLUSION: The recombinant plasmid pET30a(+)-FhCL
      has been constructed, which shows high antigenicity.

PMID- 19852357
TI  - [Two cases of trichinellosis in Nyingchi prefecture of Tibet].

PMID- 19852358
TI  - [In vitro influence of multi-frequency focused ultrasound on the ultrastructure
      of Echinococcus granulosus hydatid cysts].
AB  - OBJECTIVE: To investigate the change of Echinococcus granulosus hydatid cysts in
      vitro treated with single-frequency and multi-frequency focused ultrasound.
      METHODS: Mice were inoculated with echinococcus protoscolices from infected
      sheep, and sacrificed after one year. Forty cysts (about 2 cm in diameter) were
      taken from infected mice, and randomly divided into four groups. Cysts in the
      control group were immediately opened, fixed with 3% glutaraldehyde solution, and
      frozen. Cysts in groups A, B and C were treated with transducer No. 2 (4W),
      transducer No. 2 (4W) +No. 3 (5W), and transducer No. 1 (4W) +No. 2 (4W) +No. 3
      (5W), respectively. After irradiated for 1 minute, the cysts were all fixed and
      refrigerated, then observed by naked eyes, transmission electron microscopy and
      scanning electron microscopy. RESULTS: The wall of hydatid cyst in the
      experimental groups became thicker and less transparent. Images from the
      transmission electron microscopy showed more serious damage of cyst wall with the
      increase in ultrasonic power and irradiation time. The fiber of the laminated
      layer became thicker and disordered, the nucleus in germinal layer became swollen
      and broken, the mitochondria were destroyed remarkably and the microvillus got
      shorter, fractured or even disappeared. In some occasions, only cell debris and
      broken nucleolus left. Scanning electron microscopy also demonstrated that with
      the increase in ultrasound power and irradiation time, the damage of the cyst
      wall became more serious even the normal structure was completely destroyed.
      CONCLUSION: Multi-frequency focused ultrasound causes significant damage of the
      Echinococcus granulosus hydatid in vitro, and the damage level is related to the
      ultrasound power and irradiation time.

PMID- 19852359
TI  - [Transcription profile of PfRON4 gene in Plasmodium falciparum erythrocytic
      stage].
AB  - OBJECTIVE: To reveal the transcription profile of PfRON4 gene in Plasmodium
      falciparum erythrocytic stage. METHODS: P. falciparum schizonts were purified by
      differential centrifugation on a Percoll-sorbitol gradient, after which the
      released merozoites were allowed to invade uninfected erythrocytes for 4 hours
      before the clearance of all remaining schizonts using 5% D-sorbitol. The cultured
      synchronous parasites were harvested for RNA assay immediately, 24 hours later,
      and then at every 6th hour. PfRON4 and related genes (PfAMA1 and PfRhopH2) were
      amplified by real-time PCR for establishing standard curves to evaluate the copy
      number of genes. RESULTS: P. falciparum parasites were well synchronized. Those
      quantative analyses were reliable because the R value of standard curves were
      more than 0.98 and the melting curve showed a single peak. When parasites were in
      the schizont stage, PfRON4 gene transcription reached a peak in 36-40 hours after
      invasion. CONCLUSION: The transcription of PfRON4 peaks at mature schizont stage,
      suggesting that the PfRON4 gene may involve in erythrocyte-invasion of P.
      falciparum.

PMID- 19852360
TI  - [Construction and immunoscreening of cDNA library of Babesia orientalis].
AB  - OBJECTIVE: To construct a cDNA library for Babesia orientalis and screen
      immunologically positive clones. METHODS: Total RNA of B. orientalis in red blood
      cells from an infected calf was isolated. cDNA was synthesized by reverse
      transcriptase, amplified by PCR and ligated into lambdaTriplEx2 vector. The
      recombined vectors were packaged and the unamplified cDNA library was
      constructed. The cDNA library was then amplified and immunologically screened
      with rabbit anti-B. orientalis serum. The recombinant lambdaTriplEx2 of positive
      clones were converted to the corresponding recombinant pTriplEx2. The inserted
      fragments were identified by PCR amplification. The plasmids were sequenced and
      compared against GenBank database by Blast. RESULTS: The titer of the unamplified
      library was 2.0 x 10(6) pfu/ml. The inserted fragment length of the library
      ranged from 500 to 3,000 bp, and the recombination efficiency accounted for
      98.8%. The titer of the amplified library was 5.8 x 10(8) pfu/ml. Three positive
      clones were selected by serum immunological screening and named B04, B05, and
      B41, respectively. The inserted fragments of the B04, B05 and B41 were about
      1,300 bp, 1,000 bp, and 2,400 bp, respectively. Sequence analysis revealed that
      the 3 clones contained open reading frames. Blast results showed that they were
      highly homologous to the nuclear movement protein gene, the hypothetical protein
      gene and the heat shock protein 70 (HSP70) gene, respectively. The deduced amino
      acid sequences of B04, B05 and B41 contained 310, 192 and 647 amino acid
      residues, with Mr of 34,000, 21,000, and 70,700, respectively. CONCLUSION: A
      qualified cDNA library of B. orientalis has been constructed and three positive
      clones of B. orientalis discovered.

PMID- 19852362
TI  - [In vitro cultivation model of Cryptosporidium parvum in MDCK cells and its
      development].
AB  - OBJECTIVE: To develop an in vitro culture system for Cryptosporidium parvum in
      Madin-Darby canine kidney (MDCK) cell and observe its life cycle (from desquamate
      to oocyst). METHODS: Oocysts of C. parvum were co-cultured with MDCK cells in
      vitro. Culture condition was optimized and the life cycle of C.parvum
      investigated. RESULTS: The optimal culture conditions for C. parvum in MDCK cells
      were 2.0 x 10(5) cells cultured for 12 h, and infected by 1.0 x 10(5) oocysts in
      the Dulbecco's Modified Eagle Medium with 5% FBS. Following 72 h co-culture,
      desquamate, sporozoites, trophozoites, meronts, microgametocytes,
      macrogametocytes, zygote, thin-wall oocyst, and thick-wall oocyst appeared
      orderly. Between the 60th and 72nd hour, many oocysts emerged. Inoculated by the
      C. parvum-infected cell culture supernatant at the 48th hour, the
      immunosuppressed mice became infected. CONCLUSION: The culture system provides a
      model for propagation of the parasites and demonstrates a complete in vitro life
      cycle of C. parvum.

PMID- 19852361
TI  - [Therapeutic effect of tribendimidine, artesunate and praziquantel administered
      to hamsters infected with Clonorchis sinensis].
AB  - OBJECTIVE: To observe the effect of tribendimidine, artesunate and praziquantel
      in treatment of hamsters (Mesocricetus auratus) infected with Clonorchis
      sinensis. METHODS: A total of 93 hamsters, each infected with 30 C. sinensis
      metacercariae, were treated intragastrically with above-mentioned drugs at a
      single dose. (1) In order to observe the effect of the drugs against juvenile C.
      sinensis, 20 out of 31 infected hamsters were randomly divided into 4 groups (5
      hamsters per group) 14 d post-infection: artesunate 300 mg/kg, tribendimidine 100
      mg/kg or 200 mg/kg, and praziquantel 200 mg/kg. Other 6 hamsters were divided
      equally into 2 groups 24 d post-infection and treated with tribendimidine 200
      mg/kg and artesunate 300 mg/kg, respectively. The remained 5 untreated hamsters
      served as control. (2) Twenty-two hamsters were randomly divided into 5 groups (4
      5 hamsters per group) 28 d post-infection and treated with tribendimidine 25
      mg/kg or 50 mg/kg, artesunate 25 mg/kg and praziquantel 50 mg/kg, respectively.
      Other untreated hamsters served as control. (3) Forty hamsters 28 d after
      infection were randomly divided into 8 groups (4-6 hamsters per group) and
      treated with tribendimidine 50 mg/kg, 100 mg/kg or 200 mg/kg, artesunate 100
      mg/kg or 200 mg/kg, praziquantel 100mg/kg or 200mg/kg, respectively. The remained
      hamsters served as control. All hamsters were sacrificed 14 d post-treatment and
      worms were recovered from the bile duct and liver tissue. The mean worm burden
      and its reduction were calculated. The differences of mean worm burden between
      each treated group and the corresponding control were analyzed statistically.
      RESULTS: In hamsters infected with 14-d-old C. sinensis and treated orally with
      tribendimidine at a single dose of 100 or 200 mg/kg, the mean worm burdens were
      significantly lower than that of the control (P<0.01) with a worm reduction of
      90.6% and 85.9% respectively. The mean worm burden obtained from the infected
      hamsters treated with praziquantel at a single dose of 200 mg/kg was also
      significantly lower than that of the control (P<0.05) with a worm reduction of
      71.9%. However, the difference of mean worm burden between artesunate and control
      groups was not statistically significant. The juvenile parasites developed into
      adult worms 24 d after infection. By administering tribendimidine 200 mg/kg to
      the adult C. sinensis-infected hamsters, the mean worm burden was significantly
      lower than that of the control (P<0.01) with a worm reduction of 89.8%. Whilst
      the administration of artesunate at a higher dose of 300 mg/kg, all hamsters were
      cured. Further tests indicated that tribendimidine in a lower dose of 25 mg/kg to
      the hamsters 28 d after infection resulted in a significantly lower mean worm
      burden compared to the control (P<0.05) with a worm reduction of 71.8%. With an
      increased dose of tribendimidine 100 mg/kg, all hamsters were cured. The worm
      reduction was only 20.0% and 56.4% when 25 mg/kg and 100 mg/kg of artesunate were
      administered. With 200 mg/kg artesunate, the worm reduction reached as high as
      98.5% and the mean worm burden was significantly lower than that of the control
      (P<0.01). Furthermore, administration of praziquantel at a dose of 100 mg/kg or
      200 mg/kg at 28 d post-infection resulted in a significantly lower mean worm
      burden than that of the control (P<0.05) with a worm reduction of 78.9% and 83.5%
      respectively. CONCLUSION: In hamster model, tribendimidine and praziquantel
      exhibit promising effect against both juvenile and adult C. sinensis, while
      artesunate is only efficacious against adult worms.

PMID- 19852363
TI  - [Application of magnetic particle antibody immunoassay in detection of anti
      Schistosoma japonicum egg antibody].
AB  - OBJECTIVE: To establish a magnetic particle antibody immunoassay (MPAIA) for the
      detection of specific antibody in sera of schistosomiasis patients. METHODS:
      Fluorescein isothiocyanate (FITC) was used to label Schistosoma japonicum soluble
      egg antigen (Sj-SEA). Anti-human IgG coated with alkaline phosphatase (ALP) as
      enzyme-labeled second antibody, and magnetic beads were coupled with sheep anti
      FITC antibody as solid phase. Phenolphthale in monophosphate was used as
      substrate to set up MPAIA for the detection. Serum samples from cases with
      schistosomiasis or other helminth infections were tested. RESULTS: The positive
      rate of MPAIA was 96.7% (116/120) with the sera of S. japonicum-infected cases.
      No cross reaction was observed with sera of trichinellosis, paragonimiasis or
      cysticercosis cases. The positive titer with reference sample was 1: 1,600. The
      precision was lower than 10%. The MPAIA tips can be stored at 4 degrees C for 12
      months. CONCLUSION: MPAIA shows a high sensitivity, proper specificity and long
      term validity for schistosomiasis detection.

PMID- 19852364
TI  - [Cloning, sequencing of G3PD gene from Brugia malayi and prediction of B cell
      epitopes in its amino acid sequence].
AB  - Specific primers were designed and synthesized based on the reported
      glyceraldehyde-3-phosphate dehydrogenase (BmG3PD) gene of Brugia malayi (GenBank
      Accession No. U18137). Total RNA was extracted from Brugia malayi and its BmG3PD
      gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR).
      The PCR product was purified and cloned into plasmid pGEM-T, then transformed
      into Escherichia coli DH5alpha. The recombinant plasmids were screened and
      identified by digestion with restriction enzyme and PCR amplification. The
      positive recombinant plasmid pGEM-T-BmG3PD was confirmed by sequencing and
      homology comparison. Five parameters and methods were used to predict B-cell
      epitopes in amino acid sequence of BmG3PD. The amplified DNA fragment (1,020 bp)
      had a high identity of 99% with the BmG3PD gene sequence of Brugia malayi. B-cell
      epitopes of BmG3PD were probably at or adjacent to 22-36, 242-255, 303-318 and
      326-336 in its amino acid sequence.

PMID- 19852365
TI  - [In vitro culture of Toxoplasma gondii tachyzoites in HFF and HeLa cells].
AB  - OBJECTIVE: To study the proliferation of Toxoplasma gondii RH strain tachyzoites
      in human foreskin fibroblast (HFF) cells and HeLa cells. METHODS: HFF cells and
      HeLa cells were cultured in 35 mm cell culture dishes with glass cover slip.
      Confluent cells were co-cultured with tachyzoites which purified by 3 microm
      filter membrane. At 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, and 96 h after co
      culture, the invasion of tachyzoites into the cells and proliferation in cells
      were observed with Giemsa staining. RESULTS: In 4 h after co-culture, there were
      dozens of T. gondii tachyzoites in the HFF cells. At 24 h many pseudocysts
      emerged. At 72 h most of the cells were destroyed by tachyzoites. While cultured
      in HeLa cells for 8 h, there were only 3-5 tachyzoites in one cell, and
      pseudocysts emerged at 48 h. At 96 h after co-culture, most cells were destroyed.
      CONCLUSION: Toxoplasma gondii tachyzoites can be cultured in HFF cells and HeLa
      cells. The proliferation of tachyzoites in HFF cells was quicker than that in
      HeLa cells.

PMID- 19852366
TI  - [Comparative study on morphology and development of two species of Raillietina
      from chicken].
AB  - OBJECTIVE: To compare the morphological features and the development of
      Raillietina echinobothrida and R. tetragonal from chicken. METHODS: The parasites
      were collected from chicken digestive tract, and 3-5 fresh scolex fragments were
      separated. After being washed, fixed, dried, glided by ion sputter, the specimens
      were observed and photographed under scanning electron microscope. The cestodes
      were immersed in tap water for natural stretch and proglottids of different
      development stages were used for serial paraffin sections by conventional method,
      stained with HE and mounted in gum. Morphological observation was carried out by
      optical microscopy. The naturally stretched worms were pressed between two glass,
      stained, dehydrated, cleared, mounted, and observed under optical microscope.
      RESULTS: The body of the two species consists of scolex, neck and strobilae. Each
      mature proglottid showed a set of male and female reproductive system and genital
      openings on one side. Testes located on both sides of the ovary and behind
      vitellarium. A complete worm of R. echinobothrida was shorter than R. tetragonal,
      with a round scolex and suckers and short neck. The ovary looked like leaf and
      vitellarium was in kidney-shape. There were many acid particles and calcareous
      corpuscles in gravid proglottids. Egg capsule showed no clear boundary and
      contained only one egg. However, the scolex and suckers of R. tetragonal were
      oval in shape, and the neck was long and thin. The ovary was flower-like. Each
      egg capsule contained 4-12 eggs and many calcareous corpuscles, each of which was
      surrounded by a membrane. The male reproductive system matures first in both
      species. As the two reproductive systems matured, the proglottids became gravid
      after fertilization. The formation of egg capsule in the two species was similar.
      CONCLUSION: There are no significant morphological and development differences
      between the two species of Raillietina.

PMID- 19852367
TI  - [An epidemiological survey of visceral leishmaniasis in Hamangou coal mine area
      of Korla City, Xinjiang].
AB  - OBJECTIVE: To investigate the epidemiological status of visceral leishmaniasis in
      Hamangou coal mine area of Korla City of Xinjiang Uygur Autonomous Region.
      METHODS: Based on a hint of possible existence of patients, a retrospective
      survey was carried out house by house to find cases with suspected signs/symptoms
      of the disease. Meanwhile, a survey on current status was conducted, including
      physical examination (liver and spleen palpation) to those less than 15 years
      old, leishmanin skin test and rk39 immunochromatographic strip test for part of
      the residents. Bone marrow smears were examined for the cases with clinical
      signs/symptoms and positive rk39 strip test. Sandflies were collected using
      routine methods in and around the area, identified, and dissected to find
      infection of promastigotes. RESULTS: Leishmanin skin test was performed in 185
      people with a positive rate of 21.1% (39/185), 39 out of 140 local residents who
      have lived there for more than 6 years showed positive (27.9%), while all
      residents who have lived less than 6 years and children under 5 years old were
      negative. Of the 81 children under 15 years old with a negative skin test, one
      showed positive for rk39 strip test, and leishmania body was found in the bone
      marrow smear of this case, so confirmed as visceral leishmaniasis. 12 sandflies
      were identified as Phlebotomus alexandri, and natural infection with
      promastigotes was found in one sandly. CONCLUSION: The investigation confirms
      that visceral leishmaniasis is endemic in the Hamangou coal mine area.

PMID- 19852368
TI  - [Diversity of ectoparasites on Niviventer confucianus in the surrounding areas of
      Erhai Lake].
AB  - OBJECTIVE: To understand the species diversity of ectoparasites on Niviventer
      confucianus in the surrounding areas of Erhai Lake. METHODS: Small mammals were
      randomly captured in 12 investigated sites surrounding Erhai Lake with baited
      mouse cages. The cage-traps were examined and re-baited each morning. Trapped
      small mammals were brought to the laboratory for identification according to
      color, body length, ear length, hind foot length. All ectoparasites on the
      surface of the hosts were collected and identified. The constituent ratio (C),
      prevalence (P) and average ectoparasite abundance (A) were used to evaluate the
      prevalence and density of ectoparasites. Non-parametric Mann-Whitney U-test was
      used to test differences in the abundance and richness of ectoparasites between
      female and male hosts. Spearman correlation analysis was used to analyze the
      relationship between ectoparasites and the body parameters of hosts. RESULTS:
      Eighty-nine individuals of N. confucianus were captured, of which 79% were found
      infested with 51 species of ectoparasites, including 31 species of chigger mites,
      13 species of mesostigmatid (gamasid) mites, 4 species of fleas and 3 species of
      sucking lice. Walchia ewingi Fuller (66.2%), Laelaps turkestanicus Lange (38.5%),
      Paradoxopsyllus custodis Jordan (42.9%) and Hoplopleura pacifica (80.1%) were the
      most predominant species of chigger mites, gamasid mites, fleas, and sucking
      lice, respectively. Non-parametric Mann-Whitney U-test showed that there was no
      significant difference between male and female hosts on the species richness and
      abundance of total ectoparasites, chigger mites, sucking lice, fleas or gamasid
      mites. Spearman correlation analysis showed that the abundance and species of
      total ectoparasites, chigger mites, sucking lice, fleas or gamasid mites were not
      correlated with the body weight of hosts. CONCLUSION: There is a high speices
      diversity of ectoparasites on N. confucianus. Sucking lice, fleas, chiggers and
      gamasid mites are the main ectoparasites.

PMID- 19852369
TI  - [Clinical analysis of 78 cases of parasitic encephalopathy].
AB  - OBJECTIVE: To investigate the epidemiology, clinical characteristics, therapeutic
      approaches and outcomes of parasitic encephalopathy. METHODS: A retrospective
      study was carried out to analyze 78 cases of parasitic encephalopathy in Huashan
      Hospital between June 2003 and June 2008. RESULTS: There were 52 male and 26
      female patients with a mean age of (34.5+/-11.4) years. Among these patients,
      32.1% (25/78) had a history of eating raw, neurocysticercosis accounted for 78.2%
      (61/78), cerebral sparganosis 15.4% (12/78), cerebral paragonimiasis 3.8% (3/78),
      and cerebral toxoplasmosis 2.6% (2/78). The common clinical features were
      epilepsy, headache, nausea, vomiting, vision and hearing loss, facial paralysis
      and mental retardation. Internal medical therapy resulted in an improvement in
      69.2% of the patients. 7 out of 9 patients got improved or cured by combined
      surgical and internal medical treatment. 42 cases were diagnosed as parasitic
      encephalopathy while 36 cases (46.1%) were once misdiagnosed as other disorders.
      CONCLUSION: Parasitic encephalopathy is associated with a history of eating raw,
      with a high rate of misdiagnosis. Internal medicine combined with surgery is an
      effective way for the therapy.

PMID- 19852370
TI  - [Expressed sequence tags (ESTs) analysis of Angiostrongylus cantonensis].
AB  - A total of 1,277 ESTs of Angiostrongylus cantonensis were downloaded from GenBank
      and analyzed with BlastX. SignalP V3.0 analysis was applied to predict potential
      putative antigen or allergen relative proteins with N-terminal secreted signal
      peptides or signal anchors. BlastX analysis showed that there were 614 ESTs
      scored more than 100, of which 14 were identical with A. cantonensis, 60 ESTs did
      not match any proteins in the databases. The identified 614 ESTs could be grouped
      into 10 categories, 80 ESTs expressed 22 antigen or allergen relative proteins,
      in which 12 had N-terminal secreted signal peptides and 3 had signal anchors.

PMID- 19852371
TI  - [Human plerocercoidosis and sparganosis: II. A historical review on pathology,
      clinics, epidemiology and control].
AB  - This article is the second part of the previous review and summarizes the
      research advances on pathology, clinical manifestation, diagnosis, treatment,
      epidemiology, and control of human plerocercoidosis and sparganosis.

PMID- 19852373
TI  - [Impact of climate warming on schistosomiasis transmission and application of
      relative research techniques].
AB  - Oncomelania hupensis is the intermediate host of Schistosoma japonicum, and its
      distribution is consistent with that of schistosomiasis. Temperature is an
      essential environmental factor for the survival of snails. Therefore, it is
      important to study the impact of climate warming on snail-breeding and
      schistosomiasis transmission. This paper reviews the importance of climate
      warming to snail breeding and the spreading of the disease, and the application
      of relative research techniques.

PMID- 19852372
TI  - [Application of molecular marker techniques in taxonomic identification of
      parasites].
AB  - Different subspecies or strains of the same species produce varied clinical
      manifestations. The clarification of parasite taxonomy is useful for the
      researches of their biology, epidemiology and control. DNA molecular markers have
      the advantages of high polymorphism, non-pleiotropy, and clear identifying
      alleles, etc. This paper summarizes the first generation (restriction fragment
      length polymorphism, random amplified polymorphic DNA), second generation (simple
      sequence repeat-anchored PCR, inter-simple sequence repeat) and third generation
      (single nucleotide polymorphism) molecular marker techniques, and their
      application in taxonomic identification of parasites.

PMID- 19852374
TI  - [Facial Demodex infection among college students in Tangshan].
AB  - A survey indicated that the prevalence of Demodex infection among 512 college
      students in Tangshan was 36.3% (186/512), that of males and females was 39.3%
      (81/206) and 34.3% (105/306) respectively (P>0.05). The infection of Demodex
      folliculorum accounted for 82.3% (153/186), followed by D. brevis (7.5%, 14/186)
      and mixed infection (10.2%, 19/186). The prevalence was 47.0% (93/198) in
      subjects with oily skin, 26.6% (37/139) in those with dry skin, and 33.9%
      (56/165) in mixed-type skin (P<0.05). Subjects with facial diseases (62.0%,
      75/121), such as rosacea and acne, were more likely to be infected with Demodex
      than those with healthy skin (27.6%, 80/290) (P<0.05). Prevalence in those lived
      in humid environment (67.9%, 95/140) was higher than those lived in the
      desiccating environment (24.5%, 91/372) (P<0.05).

PMID- 19852375
TI  - [Are parasitic infections advantageous to humans?].
AB  - Humans are negatively affected by parasitic infection. However, recent researches
      revealed that to some extent, parasitic infections are advantageous to humans.
      Parasitic infections are found to benefit patients of inflammatory bowel disease,
      diabetes mellitus, autoimmune disease and allergic disorder. Furthermore, they
      promoted studies on pathogenesis of these diseases, and therefore on safe and
      effective therapeutic strategy. In addition, by taking the Caenorhabditis elegans
      as model organism, researchers have made a breakthrough in the area of life
      science, including signal transduction, functional genomics and drug screening.

PMID- 19852376
TI  - [Investigation on the prevalence of gastrointestinal parasites in pet hamsters].
AB  - One hundred and fifty-three fecal samples of pet hamsters (Mesocricetus auratus,
      Phodopus sungorus, P. campbelli and P. roborovskii) were collected from a pet
      market in Zhengzhou, and examined by Sheather's sugar flotation, modified acid
      fast staining and Lugol's iodine-solution staining. The prevalence of parasites
      was 70.7% (41/58), 96.7% (59/61), 83.9% (26/31), and 100% (3/3) respectively,
      with an overall prevalence of 84.3%. Eggs, cysts or oocysts of Cryptosporidium
      sp. (15.0%), Giardia sp. (22.2%), coccidian (2.0%), Hymenolepis nana (31.4%),
      Hymenolepis diminuta (25.5%), Syphacia spp. (41.8%), Aspiculuris tetraptera
      (7.2%) and undetermined Trichurata nematode (18.3%) were found from the samples.
      The results suggest that pet hamsters may be infected and transmit several
      zoonotic parasites.

PMID- 19852377
TI  - [Transmission dynamic model for echinococcosis granulosus: establishment and
      application].
AB  - A dynamic model of disease can be used to quantitatively describe the pattern and
      characteristics of disease transmission, predict the disease status and evaluate
      the efficacy of control strategy. This review summarizes the basic transmission
      dynamic models of echinococcosis granulosus and their application.

PMID- 19852378
TI  - [Molluscicidal effect and toxicity of META-Li on Oncomelania snails in the
      mountain area].
AB  - The molluscicidal effect and toxicity of META-Li were evaluated and compared with
      niclosamide in Yushan county of Jiangxi Province in August 2008. There are four
      groups named as META-Li ridge group (1 g/m2), META-Li field group (1 g/m2),
      niclosamide group (2 g/m2) and control group. At 3 d, 7 d, 15 d and 2 months
      after drugs sprayed, the corrected mortalities of snails in the 3 groups were
      considerably higher than those of control (P<0.05). The corrected mortalities in
      META-Li field group were significantly lower than those of META-Li ridge group
      and niclosamide group (P<0.05). No adverse effect was observed to non-target
      organisms in META-Li groups, while fishes, snails and frogs all died at the first
      day after treated with niclosamide.

PMID- 19852379
TI  - [Bibliometric analysis of the Chinese Journal of Parasitology and Parasitic
      Diseases in 2006-2008].
AB  - The published articles and citation of the Chinese Journal of Parasitology and
      Parasitic Diseases in 2006-2008 were statistically analyzed. Among 431 papers
      published in the three years, original articles and experimental researches
      occupied 31.8% and 17.6%, respectively. Authors were mainly from
      colleges/universities (53.8%) and institutions for disease control (34.1%). 71.5%
      of the articles received financial supports from research funds/foundations.
      Reference citation was mostly from periodicals. The average Price index was
      46.5%. This Journal possesses a group of stable and qualified authors, covers
      substantial content with relatively broad citation, and is an important source of
      information in parasitological research.

PMID- 19852380
TI  - Image, text and Observatio: the Codex Kentmanus.
AB  - This paper examines the inter-relationship between image, text and object in the
      Codex Kentmanus, which is one of the earliest records of the plants in the
      botanical garden at Padua, studied by Johannes Kentmann (1518-77). The manuscript
      shows that "observation" for Kentmann involved a gradual process of assimilating
      knowledge from other physicians, apothecaries, and books in order to make the
      plants which were originally encountered at a specific time and place into a more
      generalised object of study for learned physicians.

PMID- 19852381
TI  - [The pastor Jean-Frederick Oberlin (1740-1826) and medicine. Scientific and human
      aspects].
AB  - J.Fr. Oberlin was a Lutheran clergyman in a remote valley of Vosges between
      Alsace and Lorraine. He is well-known for his numerous philantropic acrivities
      and his spiritual living. In his youth he acquired some knowledge in medicine and
      botany which allowed him to cure many people whose well-being and vitality
      improved during the 60 years of his life at the Ban de la Roche. He profited of
      progress of medicine in the XVIIIth and XIXth centuries and the exceptionnel
      botanical abundance of the valley. There are little information about the stock
      and the preparation of drugs but Oberlin is the source of a great liveliness for
      medical researchers about medicine of his epoch.

PMID- 19852383
TI  - [Jean-Baptist Tyrbas de Chamberet (1779-1870). Military doctor, actor and witness
      of his time].
AB  - As military physician Tyrbas de Chamberet was a witness of his time. In 1804 he
      arrived in Paris and became a medical student. Later he followed the army in
      Italy, Spain and took part to a mission in Poland where cholera epidemic had
      broken. As chief of the Hospital Val-de-Grace he knew people around Larrey and
      Broussais. In his writings he gave some advices for the organisation of the
      Military Health Service according to the different governments as well as the
      characters of his contemporaries.

PMID- 19852382
TI  - [The death of the king Henry IV (May 14th, 1610). Analysis of the report of
      postmortem examination of Jacques Guillemeau].
AB  - Henri IV, King of France, was killed on Friday, May 14th, 1610 in Paris, inside
      his partially open coach. The autopsy was performed the following day by Jacques
      Guillemeau, whose report was published in 1612. The murderer's position was
      deduced from the direction of the lethal second wound. We suppose that Ravaillac
      used his left hand (he was an ambidexter) hitting Henri IV under the left arm;
      the King was bent on his right side after the first wound, a superficial one.
      Ravaillac jumped up on a post by his left foot, then on the nave of the left-back
      wheel with his right foot and turning, gripped something high on the coach and
      hit with his long knife the left side of the king's chest. The direction of the
      wound was 40 degrees posterior and 30 degrees ascending. The pulmonary
      perforation involved a haemoptysis, an inability to speak and a bilateral
      pulmonary inundation. The left haemothorax was very probably associated to an
      haemopericardium and an haemomediastinum leading to a rapid collapse with a loss
      of consciousness which could not last than ten or fifteen minutes before death.

PMID- 19852384
TI  - [A curious certificate recalling the abolition of the Faculty of Medicine of
      Paris on November 21st, 1822].
AB  - The author deals with the strange certificate of the surgeon Nicolas Marjolin
      about events which led to the suppression of the "Faculte de Medecine" in Paris
      on the 21st November 1822 and all the consequences of orders of King Louis XVIII.

PMID- 19852385
TI  - [Regarding the Manuscript D " Dell' occhio " of Leonardo da Vinci].
AB  - Leonardo da Vinci's Manuscript D consists of five double pages sheets, which,
      folded in two, comprise ten folios. This document, in the old Tuscan dialect and
      mirror writing, reveals the ideas of Leonardo on the anatomy of the eye in
      relation to the formation of images and visual perception. Leonardo explains in
      particular the behavior of the rays in the eye in terms of refraction and
      reflection, and is very mechanistic in his conception of the eye and of the
      visual process. The most significant innovations found in these folios are the
      concept of the eye as a camera obscura and the intersection of light rays in the
      interior of the eye. His texts nevertheless show hesitation, doubts and a
      troubled confusion, reflecting the ideas and uncertainties of his era. He did not
      share his results in his lifetime, despite both printing and etching being
      readily available to him.

PMID- 19852386
TI  - Infanticide, child rape and war in early states.

PMID- 19852387
TI  - On the roles played by psychoclasses in the evolution of parenting.

PMID- 19852388
TI  - From their cradle to your grave: how child abuse and dissociation drive violent
      crime.

PMID- 19852389
TI  - Religious fundamentalism and its impact on the female gender.

PMID- 19852390
TI  - [An ethnographic study of an Ottoman city at the end of the 18th century. Viage a
      Esmirna by Pedro Maria Gonzalez].
AB  - In the summer of 1796, Pedro Maria Gonzalez, a surgeon trained at the College of
      Cadiz, took part in an expedition commissioned by the Cadiz Consulate with the
      aim of initiating trading relationships with Smyrna, the most important
      commercial centre in the Ottoman Empire. On his return, he wrote a document to
      facilitate future business ventures by Spaniards, describing in detail the
      customs and traditions of the various social and ethnic groups that inhabited the
      city of Smyrna. In this paper, I analyse the view of the Turks held by Europeans
      in the 17th and 18th centuries and the ideological and conceptual factors
      underlying their negative opinions. I then describe the viewpoint of Gonzalez
      himself, especially in relation to Jews, the ethnic group he studied in greatest
      depth. The fact that they shared a common language, Spanish, undoubtedly
      facilitated his relationships and his close analysis.

PMID- 19852391
TI  - Alexander von Humboldt's perceptions of colonial Spanish America.
AB  - This study presents an in-depth analysis of Alexander von Humboldt's descriptions
      and critical comments on the colonial society of the different regions he visited
      during his well-known expedition through the Americas (1799-1804). The criticisms
      of colonialism that he expressed, reflecting his personal convictions, have
      already been the focal point of many studies, but Humboldt also was able to offer
      a more differentiated assessment through comparisons of regional and local
      traditions and developments. This essay focuses on his personal diaries, which
      offer many interesting comments on colonial societies. These considerations and
      impressions made during the expedition are of particular scholarly value since
      they were not subject to censorship of any kind.

PMID- 19852392
TI  - [Regenerationism, health and racial discourse: Felipe Ovilo Canales and the
      convergence between Spain and Morocco at the end of the 19th century].
AB  - The army medical officer, Felipe Ovilo Canales, was a prominent and
      representative figure in colonialist projects in Morocco during the Restoration.
      Unlike other European powers, Spain's colonial missions were mainly aimed at
      fostering and controlling the ongoing process of Moroccan administrative reform.
      In the context of this overall reform strategy, Ovilo developed a political
      discourse that affirmed the historic convergence of Spanish and Moroccan
      interests; he played a leading role in Moroccan public health through the
      Tangiers Health Authority and the Tangiers School of Military Medicine. Finally,
      he formulated a racial discourse on the "Moors" that was based on historical and
      moral rather than biological criteria.

PMID- 19852393
TI  - [Anthropology and "crisis in medicine": The pathologist M. Kuczynski-Godard (1890
      1967) and the indigenous peoples of Central Asia and Peru].
AB  - This article examines the work of the German-Peruvian physician Max
      Kuczynski/Maxime Kuczynski-Godard (Berlin 1890-Lima 1967) in rural areas of
      Central Asia (1924-26) and Peru (1938-48). The main focus of the text is on the
      scientific approach behind the specific interest of this pathologist in disease
      and health issues among native populations. Kuczynski's theoretical
      considerations are analyzed in the context of the wide controversies within the
      German medical community around a "crisis in medicine" when he was professor at
      Berlin University during the interwar years. Accordingly, his determination to
      leave the laboratory and to shift research and healthcare practice closer to
      rural populations proves to be the expression of profound epistemological and
      ethical considerations.

PMID- 19852394
TI  - Radioisotopes "economy of promises": on the limits of biomedicine in public
      legitimization of nuclear activities.
AB  - This paper aims to examine the rise and the fall of biomedicine in the public
      legitimization of the development of nuclear energy. Until the late 1950s,
      biological and medical applications of radioisotopes were presented as the most
      important successes of the peaceful uses of atomic energy. I will argue that
      despite the major financial investment, the development of the uses of
      radioisotopes and their important impact on biology and clinical practices, the
      assessment of medical uses remained relatively limited. As consequence, the place
      of biomedicine in the public legitimization of financial investment and civilian
      uses of nuclear energy began to decline from the late 1950s.

PMID- 19852395
TI  - From prophylaxis to atomic cocktail: circulation of radioiodine.
AB  - This paper is a history of iodine. To trace the trajectory of this element,
      goiter is used as a guideline for the articulation of a historical account, as a
      representation of thyroid disorders and of the spaces of knowledge and practices
      related to iodine. Iodine's journey from goiter treatment and prophylaxis in the
      late interwar period took on a new course after WWII by including the element's
      radioactive isotopes. I intend to show how the introduction of radioiodine
      contributed to stabilize the epistemic role of iodine, in both its non
      radioactive and radioactive form, in thyroid gland studies and in the treatment
      of its disorders.

PMID- 19852396
TI  - Controlling life: from Jacques Loeb to regenerative medicine.
AB  - In his 1987 book Controlling Life: Jacques Loeb and the Engineering Ideal in
      Biology, Philip Pauly presented his readers with the biologist Jacques Loeb and
      his role in developing an emphasis on control of life processes. Loeb's work on
      artificial parthenogenesis, for example, provided an example of bioengineering at
      work. This paper revisits Pauly's study of Loeb and explores the way current
      research in regenerative medicine reflects the same tradition. A history of
      regeneration research reveals patterns of thinking and research methods that both
      echo Loeb's ideology and point the way to modern studies. Pauly's work revealed
      far more than we readers realized at the time of its publication.

PMID- 19852397
TI  - The monstering of tamarisk: how scientists made a plant into a problem.
AB  - Dispersal of biota by humans is a hallmark of civilization, but the results are
      often unforeseen and sometimes costly. Like kudzu vine in the American South,
      some examples become the stuff of regional folklore. In recent decades, "invasion
      biology," conservation-motivated scientists and their allies have focused largely
      on the most negative outcomes and often promoted the perception that introduced
      species are monsters. However, cases of monstering by scientists preceded the
      rise of popular environmentalism. The story of tamarisk (Tamarix spp.), flowering
      trees and shrubs imported to New England sometime before 1818, provides an
      example of scientific "monstering" and shows how slaying the monster, rather than
      allaying its impacts, became a goal in itself. Tamarisks' drought and salt
      tolerance suggested usefulness for both coastal and inland erosion control, and
      politicians as well as academic and agency scientists promoted planting them in
      the southern Great Plains and Southwest. But when erosion control efforts in
      Arizona, New Mexico and Texas became entangled with water shortages, economic
      development during the Depression and copper mining for national defense during
      World War Two, federal hydrologists moved quickly to recast tamarisks as water
      wasting foreign monsters. Demonstrating significant water salvage was difficult
      and became subsidiary to focusing on ways to eradicate the plants, and a federal
      interagency effort devoted specifically to the latter purpose was organized and
      continued until it, in turn, conflicted with regional environmental concerns in
      the late 1960s.

PMID- 19852398
TI  - Frits Went's atomic age greenhouse: the changing labscape on the lab-field
      border.
AB  - In Landscapes and Labscapes Robert Kohler emphasized the separation between
      laboratory and field cultures and the creation of new "hybrid" or mixed practices
      as field sciences matured in the early twentieth century. This article explores
      related changes in laboratory practices, especially novel designs for the
      analysis of organism-environment relations in the mid-twentieth century. American
      ecologist Victor Shelford argued in 1929 that technological improvements and
      indoor climate control should be applied to ecological laboratories, but his
      recommendations were too ambitious for the time. In the postwar period Frits W.
      Went, plant physiologist at the California Institute of Technology, created a new
      high-tech laboratory, dubbed a "phytotron", in the hope that it would transform
      plant sciences by allowing for unprecedented control of environmental variables.
      Went's aspirations, the research conducted in his laboratory, and its impact in
      initiating an international movement, are considered. Went's laboratory can be
      seen as a "hybrid culture" evolving in the laboratory, complementing and
      intersecting with some of the field practices that Kohler describes. It was also
      a countercultural movement against the reductionist trends of molecular biology
      in the 1950s and 1960s. By considering the history of the laboratory in relation
      to field sciences, we can explore how new funding sources and cross-disciplinary
      relations affected the development of field sciences, especially in the postwar
      period.

PMID- 19852399
TI  - Subtypes of alcohol and intimate partner violence: a latent class analysis.
AB  - The investigation explored whether subtypes of relapse to violence exist for
      different levels of intimate partner violence and drinking behavior among men who
      relapse to both alcohol and violence after alcoholism treatment. Male clients
      entering an alcoholism treatment program who reported at least one incident of
      intimate partner violence and their female partners (N = 294) were recruited for
      participation. Data were analyzed using a latent class analysis of mixture model.
      Findings revealed that two classes of violence best described the sample of men
      that relapsed to violence. Class 1 contained males who had perpetrated more days
      of violence, relapsed to violence faster, more frequently relapsed to alcohol,
      and had a higher percentage of males identified as meeting diagnostic criteria
      for antisocial personality disorder compared to those in class 2.

PMID- 19852400
TI  - The relationship between dating violence and psychosocial problems in a sample of
      adolescent pregnancy termination patients.
AB  - The relationship between dating violence and 13 psychosocial problems,
      conceptually organized into three symptom clusters--depressive, family problem,
      and posttraumatic stress--was investigated in a sample of adolescent pregnancy
      termination patients, ages 14 to 21. Results of a multivariate multiple
      regression analysis indicated that, after controlling for age, ethnicity, general
      aggression problems, and problems with peers, dating violence was significantly
      related with the symptoms clusters. At the univariate level, the results
      suggested that dating violence was significantly related with self-esteem
      problems, guilt, and suicidal thinking from the depressive symptoms cluster and
      with guilt and stress from the posttraumatic stress cluster. The implications of
      these findings are discussed.

PMID- 19852401
TI  - The domestic violence home-visit intervention: impact on police-reported
      incidents of repeat violence over 12 months.
AB  - The domestic violence home-visit intervention (DVHVI) provides home visits by
      police-advocate teams within 72-hours of domestic incident to provide safety,
      psychoeducation, mental health, legal, or additional police assistance. Clinical
      and police record data were collected for 512 cases, and repeat calls to the
      police were tracked for 12 months. Analyses revealed that women who engaged with
      the DVHVI were more likely to contact the police for subsequent events than those
      who received no or minimal DVHVI contact. Hispanic women served by Spanish
      speaking advocate-officer teams were the most likely to utilize services and call
      the police for subsequent incidents.

PMID- 19852402
TI  - Social reactions to rape: experiences and perceptions of women rape survivors and
      their potential support providers in Dar es Salaam, Tanzania.
AB  - Social reactions to rape are socioculturally determined and have a strong
      influence on the coping and recovery of the survivor. The existing knowledge on
      social reactions emanates from Western countries with limited research attention
      on non-Western populations, particularly sub-Saharan Africa. We aimed to
      establish the types and perceptions of social reactions that are expressed to
      rape survivors and people's intentions to express them to survivors of varied
      social backgrounds in Tanzania. Using triangulation of research methods,
      experiences of social reactions among rape survivors (n = 50) and nurses (n = 44)
      from a community in Tanzania were explored, and the intentions to express typical
      social reactions to rape survivors of different social backgrounds were
      established from a representative community sample (n = 1,505). Twelve typical
      social reactions were identified with the positive reactions more commonly
      mentioned than the negative reactions. Nondisclosure of rape events and
      distracting the survivor from the event were perceived as both positive and
      negative. A commercial sex worker was most vulnerable to negative reactions. The
      cultural influences of social reactions and implications for practical
      applicability of the results are discussed.

PMID- 19852403
TI  - Age, period, and cohort effects on intimate partner violence.
AB  - This study sought to determine if the recent secular decrease in reported
      intimate partner violence (IPV) in women was due to cohort or period effects.
      Women ages 18 to 64 were interviewed about IPV during their adult lifetimes. The
      lifetime prevalence of any IPV was 42%. Regardless of birth cohort, IPV was most
      common among women in their mid-20s to early 30s. After adjusting for cohort and
      period effects, women 26 to 30 had the highest risk of any IPV; risk decreased
      with age. Younger birth cohorts were at decreased risk for IPV. The estimated
      risk is lowest for those born between 1966 and 1975, with 31% lower risk of IPV
      than those born in 1946-1955. There was a substantial drop in IPV for all age
      groups beginning in the 1990s.

PMID- 19852404
TI  - Examining the correlates of aggression among male and female Vietnam veterans.
AB  - This study examined the correlates of general aggression among a nationally
      representative sample of male and female Vietnam veterans (N = 1,632). Findings
      indicated that the rates of aggression for men and women were 41% and 32%,
      respectively, and men appeared to perpetrate relatively more acts of severe
      aggression. Correlates of aggression for men included lower socioeconomic status
      and age, minority status, unemployment, degree of exposure to the malevolent war
      zone environment and perceived threat in the war zone, posttraumatic stress
      disorder, antisocial personality disorder, major depressive episode, alcohol
      abuse/dependence, and drug abuse/dependence. For women, only lower age and
      unemployment were associated with aggression. Findings highlight the importance
      of developing models for aggression among those experiencing military
      deployments.

PMID- 19852405
TI  - Reliability of self-reported childhood physical abuse by adults and factors
      predictive of inconsistent reporting.
AB  - Little is known about the reliability of self-reported child physical abuse (CPA)
      or CPA reporting practices. We estimated reliability and prevalence of self
      reported CPA and identified factors predictive of inconsistent CPA reporting
      among 2,256 participants using surveys administered in 1995 and 2000. Reliability
      of CPA was fair to moderate (kappa = 0.41). Using a positive report from either
      survey, the prevalence of moderate (61.8%) and severe (12.0%) CPA was higher than
      at either survey alone. Compared to consistent reporters of having experienced
      CPA, inconsistent reporters were less likely to be > or = 30 years old (vs. 18
      29) or Black (vs. White) and more likely to have < 12 years of education (vs.
      12), have no alcohol-related problems (vs. having problems), or report one type
      (vs. > or = 2) of CPA. These findings may assist researchers conducting and
      interpreting studies of CPA.

PMID- 19852406
TI  - Resource loss as a predictor of posttrauma symptoms among college women following
      the mass shooting at Virginia Tech.
AB  - We examined risk factors for posttrauma symptomatology, 2 and 6 months following
      the April 2007 mass shooting at Virginia Tech. Using a conservation of resources
      framework and a Web-based survey methodology, we prospectively evaluated the
      relations among preshooting distress, social support, resource loss, and
      posttrauma symptomatology in a sample of 293 female students enrolled at the
      university at the time of the shootings. Structural equation modeling supported
      that preshooting social support and distress predicted resource loss
      postshooting. Resource loss predicted symptomatology 2 months and 6 months after
      the shooting. Implications of the results for research and intervention following
      mass trauma are discussed.

PMID- 19852407
TI  - The long-term effects of extreme war-related trauma on the second generation of
      Holocaust survivors.
AB  - The psychological consequences of intergenerational trauma on the second
      generation of Holocaust survivors were studied in a sample of 40 nonimmigrant
      Italian Jews and compared to a control group. Differences between offspring of
      Holocaust survivors (HSO) and a comparison group were assessed by the Adjective
      Check List, Anxiety Questionnaire Scale, Defence Mechanism Inventory, and Family
      Environment Scale. Although the HSO displayed no serious psychological
      consequences, they had higher anxiety levels than controls, low self-esteem,
      inhibition of aggression, and relational ambivalence. These data partially
      confirm previous research on the topic, although the level of psychological
      distress seems to be lower in the Italian sample than in other samples of second
      generation Holocaust survivors.

PMID- 19852408
TI  - Integration of STI and HIV prevention, care, and treatment into family planning
      services: a review of the literature.
AB  - The last comprehensive literature review to examine the effectiveness of family
      planning (FP) services in delivering STI and HIV prevention and care was
      published in 2000. This review updates that report by examining evidence of the
      impact of integrating any component of STI or HIV prevention, care, and treatment
      into a family planning setting in developing countries. Forty-four reports were
      identified from a comprehensive search of published databases and "grey
      literature". The weight of evidence demonstrates that integrated services can
      have a positive impact on client satisfaction, improve access to component
      services, and reduce clinic-based HIV-related stigma, and that they are cost
      effective. Evidence of FP services reaching men and adolescents and of their
      impact on health outcomes is inconclusive. Several studies found that providers
      frequently miss opportunities to integrate care and that the capacity to maintain
      the quality of care is also influenced by many programmatic challenges. The range
      of experiences indicates that managers need to determine appropriate health-care
      service-delivery models based on a consideration of epidemiological, structural,
      and health-systems factors.

PMID- 19852409
TI  - Behavioral mechanisms in HIV epidemiology and prevention: past, present, and
      future roles.
AB  - In the 1980s, behavioral variations across geographically and socially defined
      populations were the central focus of AIDS research, and behavior change was seen
      as the primary means of controlling HIV epidemics. Today, biological mechanisms-
      especially other sexually transmitted infections, antiretroviral therapy, and
      male circumcision--predominate in HIV epidemiology and prevention. We describe
      several reasons for this shift in emphasis. Although the shift is understandable,
      we argue for a sustained focus on behavioral mechanisms in HIV research in order
      to realize the theoretical promise of interventions targeting the biological
      aspects of HIV risk. We also provide evidence to suggest that large reductions in
      HIV prevalence may be accomplished by small changes in behavior. Moreover, we
      contend that behavioral mechanisms will find their proper place in HIV
      epidemiology and prevention only when investigators adopt a conceptual model that
      treats prevalence as a determinant as well as an outcome of behavior and that
      explicitly recognizes the dynamic interdependence between behavior and other
      epidemiological and demographic parameters.

PMID- 19852410
TI  - How contraceptive use affects birth intervals: results of a literature review.
AB  - Short birth intervals can have adverse consequences for maternal and infant
      outcomes. Optimal birth spacing is often presumed to be achieved through the
      practice of family planning and use of contraceptives, yet most of the available
      research does not address explicitly the contribution of contraceptive-method use
      to birth spacing or maternal and infant survival. We conducted a systematic
      literature review to assess the body of evidence linking contraceptive use to
      birth-interval length. Fourteen studies published in English between 1980 and
      2008 met our eligibility criteria for inclusion. The findings from these studies
      are mixed but suggest that the use of contraceptives is protective against short
      birth intervals. Although results are favorable, many of the studies and
      methodologies employed are dated. More current research is needed to determine
      the impact of contraceptive-method use on birth-interval length in order to
      inform the promotion of family planning for reducing maternal and infant
      morbidity and mortality through birth spacing.

PMID- 19852411
TI  - Toward replacement fertility in Egypt and Tunisia.
AB  - Egypt and Tunisia began their fertility transition at almost identical fertility
      levels and at roughly the same time period, yet the difference in the pace of
      decline has been such that the total fertility rate (TFR) in Tunisia reached
      replacement level by the year 2001, whereas the TFR in Egypt remains above three
      live births per woman. This article draws on the secondary literature and on
      several nationally representative surveys from the two countries between 1978 and
      2005 to provide empirical evidence of the difference in the pace of fertility
      decline and to analyze the determinants of the differential. Findings include (a)
      variation across the two countries in the consistency of fertility decline among
      the segments of the population leading the transition; (b) that the success of
      each country's family planning program was influenced by the role of political
      leaders and the extent of the program's integration within socioeconomic
      development objectives; (c) that the impact of contraception on TFR decline
      became an important factor in the mid-1980s; and (d) that the greatest
      determinant of the discrepancy in the pace of fertility decline is the disparity
      in age at marriage, which rose more significantly in Tunisia than in Egypt. The
      latter finding indicates that reaching replacement fertility in Egypt hinges
      primarily on further declines in marital fertility, resulting from reduction of
      wanted fertility and from an expansion of family planning program coverage and
      improved efficiency of service delivery and use.

PMID- 19852412
TI  - Fertility decline in Paraguay.
AB  - Recent reproductive health surveys show that the fertility rate in Paraguay
      decreased precipitously from 4.3 lifetime births per woman in 1995-98 to 2.9
      births in 2001-04. In this study, we establish data consistency between the 1998
      and 2004 surveys by comparing a series of cohort-specific period rates and use
      the Bongaarts framework of proximate determinants of fertility to demonstrate
      that an increase in the contraceptive prevalence rate (CPR) between 1998 and 2004
      fully accounts for the fertility decline. Decomposition of rates shows that
      changes in group-specific CPRs explain a greater proportion of the change in the
      overall CPR than do changes in population composition by educational attainment,
      urban residence, region, and language spoken at home. Finally, we show that
      younger cohorts of women in 2004 reported ideal completed fertility desires of
      less than 2.9 births, suggesting that the fertility rate is likely to continue to
      decrease.

PMID- 19852413
TI  - Meeting the family planning needs of postpartum women.

PMID- 19852414
TI  - [The first resource physician: a simple sorter?].

PMID- 19852415
TI  - [Advantages of capillary INR monitoring for oral anticoagulation].
AB  - More and more patients are treated with long term oral anticoagulation. The time
      spent in therapeutic range is often limited since many factors affect INR. Too
      high or too low INRs increase respectively the hemorrhagic or thromboembolic
      risks. INR monitoring by a capillary device either in autonomy (self-management)
      by some selected patients or in relation with the treating physician (self
      control), allows increasing the time spent in therapeutic range. Capillary INR
      monitoring can also be made at the medical office: it is less invasive and
      provides a quicker answer than a venous INR.

PMID- 19852416
TI  - [Urinalysis: what a primary care physician needs to know].
AB  - Dipstick urinalysis is a very useful diagnostic tool in primary care when used in
      a specific context (urinary complaints, follow-up of systemic diseases, or
      pregnancy), but not as a screening instrument. Urine collection in appropriate
      conditions, together with a correct interpretation of dipstick results, reduces
      the use of microscopic urinalysis and urine culture. Leucocyturia and positive
      nitrits indicate the presence of a urinary tract infection and do not generally
      require additional tests. Persistent haematuria or proteinuria need to be further
      explored (microscopic urinalysis and 24h urine collection). Presence of crystals
      in the microscopic urinalysis reflects the precipitation of the substance
      eliminated in the urinary tract, but does not systematically indicate a disease.

PMID- 19852417
TI  - [Interpretation of 24h ambulatory blood pressure monitoring by primary care
      physicians].
AB  - Comparatively to office blood pressure measurement, 24h ambulatory blood pressure
      monitoring (ABPM) provides a more accurate evaluation of the patient's blood
      pressure and of the burden of the arterial pressure in real life. This
      measurement is better correlated with cardiovascular risk, with hypertension
      related organ damage and its changes with treatment, than does office blood
      pressure. It allows diagnosis of white coat and masked hypertension, and of
      alteration in blood pressure's circadian rhythm. This article aims to summarise
      ABPM's indications, to point out its advantages and give some key practical
      messages to realize and properly interpret this exam.

PMID- 19852418
TI  - [How to perform and interpret spirometry in primary care].
AB  - Spirometry is a simple test, which has a central role in the early diagnosis and
      management of diseases that are very prevalent and may become symptomatic late in
      their evolution. This manuscript explores all the necessary steps for an optimal
      use of spirometry (choice of equipment, quality control, technique, and
      interpretation). Spirometry is easy to perform in a primary care setting and its
      use should be encouraged among primary care physicians. We discuss the
      indications of this test in the follow up of patients and cover the situations
      that need referral to the specialist.

PMID- 19852419
TI  - [Home-based nocturnal oxymetry by the primary care practitioner].
AB  - Sleep-related disordered breathing is frequent and associated with high morbidity
      and mortality, thus representing a public health problem. Sleep apnea-hypopnea
      syndrome (SAHS) is sorely under-diagnosed. Our questioning was about the
      usefulness of a home-based overnight oxymetry organised by the primary care
      physician (PCP) for SAHS detection. It appears from our review that patients with
      snoring and excessive daytime sleepiness can benefit from this tool. Oxygen
      desaturation index less than 5/h does not rule out SAHS but makes it very
      unlikely. In accordance with the symptoms, one should refer the patient for
      complementary investigation. Besides detection, PCP has an important role to play
      in partnership with the pneumologist in helping the patient to cope with his
      respiratory device and contributing to treatment com-

PMID- 19852420
TI  - [Interpretation of exercise stress testing by primary care physicians].
AB  - Considering that angina is an important symptom of coronary heart disease,
      exercise stress testing has proven its usefulness and remains a reference exam.
      Indeed, it is reasonably reliable and accessible, even for non cardiologist
      physicians, and provides both diagnostic as well as prognostic information. In
      this article, we review the key points to know about stress testing, in
      particular patient selection and interpretation of it results. A good
      comprehension of these different aspects is likely to improve patient care and to
      help avoid, additional tests that may be unnecessary.

PMID- 19852421
TI  - [Mortuary notice...].

PMID- 19852422
TI  - [The long and very beautiful history of the condom].

PMID- 19852423
TI  - [A(H1N1): should physicians get vaccinated?].

PMID- 19852424
TI  - [Double effect of antibiotics].

PMID- 19852425
TI  - [Understanding].

PMID- 19852426
TI  - The frequency of consanguineous marriage in eastern Turkey.
AB  - The frequency of consanguineous marriage in Eastern Turkey: OBJECTIVE: The rate
      of consanguineous marriage (CM) varies depended on different factors such as
      race, characteristics of population, and religion and moral features in different
      countries. Gene frequency and genetic structure are changed by CMs. The aim of
      the present study is to assess the prevalence of CM and its effects on
      miscarriage, stillbirth, congenital malformation and ratio of newborn death.
      METHODS: This study was performed in Van region, Eastern Turkey, between
      September 2005 and April 2006. A total of 650 families from 24 districts chosen
      in accordance with the number of inhabitants were included in this study. First
      cousin marriages were accepted as a first degree CMs, sesquialter and second
      cousin marriages as second degree and marriages between distant relatives were
      accepted as a third degree CM. Monthly income of the families was classified in
      accordance with minimum wage determined by government. RESULTS: Of all families,
      224 (34.4%) had CM, and 168 (75%) had first-degree consanguinity. A lower CM rate
      was found in mothers who graduated from secondary school or upgrading (p < 0.01).
      However, no relationship was found between CM and fathers' education level. While
      a low CM rate was found in families who had two or less children (p < 0.01), high
      rate was observed in families who had five or more children. In addition, a high
      rate of miscarriage, stillbirth and mental-motor retardation was found in
      families with CM (p < 0.05). The rate of child mortality between the aged 0-2
      years was found to be higher in families with CM (p < 0.01). The higher CM rate
      was observed in families who married due to pressure or insistence of their
      families than married voluntarily (p < 0.05). CONCLUSION: Our study showed that
      CM rate was very high, 34.4%, in our region Eastern Turkey.

PMID- 19852427
TI  - Mode of inheritance in systemic lupus erythematosus in Saudi multiplex families.
AB  - Systemic lupus erythematosus (SLE) is a an autoimmune disease causing
      inflammation and injury of multiple organs like joints, skin, kidneys, eyes,
      central nervous system, heart. The etiology of SLE remains unknown. However;
      genetic component significantly contributes to the etiology of SLE. Familial SLE
      patients were defined as a family with more than one sibling diagnosed with SLE.
      The objective of the study is to describe the clinical features of the familial
      SLE and analyze the family pedigrees. Twenty-five individuals with SLE belonging
      to seven Saudi families were included. Three-generation pedigree was taken from
      the candidate families. The mean age at onset of the disease was 84.5 months
      (range: 18-144) while the mean age at diagnosis was 90.6 months (range: 24-144)
      and the mean duration of follow up was 48.5 months (range: 7-108). The proportion
      of girls was predominant (78%). Malar rash, arthritis and nephritis were the more
      frequent features. Sixteen patients had renal lesions, 10 of them had class VI
      nephritis according WHO classification. Five of the seven families are
      consanguineous reflecting the high percentage of consanguinity in our population.
      As many other autoimmune diseases, multifactorial is the most common form of
      inheritance. In the current study, the suggested mode of inheritance is autosomal
      recessive assuming Mendelian inheritance of single gene disorder.

PMID- 19852428
TI  - Double aneuploidy (48,XXY,+21) of maternal origin in a child born to a 13-year
      old mother: evaluation of the maternal folate metabolism.
AB  - The occurrence of non-mosaic double trisomy is exceptional in newborns. In this
      paper, a 48,XXY,+21 child, the parental origin of the extra chromosomes and the
      evaluation of the maternal folate metabolism are presented. The infant was born
      to a 13-year-old mother and presented with the typical clinical features of Down
      syndrome (DS). The origin of the additional chromosomes was maternal and most
      likely resulted from errors during the first meiotic division. Molecular analysis
      of 12 genetic polymorphisms involved in the folate metabolism revealed that the
      mother is heterozygous for the MTHFR C677T and TC2 A67G polymorphisms, and
      homozygous for the mutant MTRR A66G polymorphism. The maternal homocysteine
      concentration was 4.7 miromol/L, a value close to the one considered as a risk
      factor for DS in our previous study. Plasma methylmalonic acid and serum folate
      concentrations were 0.17 micromol/L and 18.4 ng/mL, respectively. It is possible
      that the presence of allelic variants for the folate metabolism and Hey
      concentration might have favored errors in chromosomal disjunction during
      gametogenesis in this young mother. To our knowledge, this is the first patient
      with non-mosaic Down-Klinefelter born to a teenage mother, resulting from a rare
      fertilization event combining an abnormal 25,XX,+21 oocyte and a 23,Y
      spermatozoon.

PMID- 19852429
TI  - The clinical effects of isochromosome Xq in Klinefelter syndrome: report of a
      case and review of literature.
AB  - We describe a male with a variant Klinefelter syndrome (KS), and trisomy Xq
      resulting from an isochromosome Xq [47,Xi(Xq)Y]. He had many characteristics of
      classical KS: bilateral atrophic testes and microcalcifications, normal
      masculinization, azoospermia, hypergonadotropic hypogonadism, elevated FSH and
      LH, normal intelligence and normal androgenization, but his stature was not
      increased. Ultrasonographic evaluation also revealed parenchymal alterations
      secondary to previous epididymo-orchitis. After initial evaluation the patient
      underwent incisional biopsy of testes which showed tubular hyalinisation, Leydig
      cell hyperplasia and Certoli cell syndrome. The i(Xq) was found in all cells
      analyzed. These findings indicate that extra copies of the long arm of X have
      phenotypic expression, even though activated only in early development. In
      conclusion, review of literature on 20 adult patients supports the view that the
      presence of an isochromosome Xq in KS has a favorable prognosis in terms of
      normal mental development and normal stature.

PMID- 19852430
TI  - Toriello-Carey syndrome in a Turkish newborn.
AB  - Toriello-Carey syndrome in a Turkish newborn: Toriello-Carey syndrome is
      characterized by agenesis of the corpus callosum, telecanthus, short palpebral
      fissures, small nose with anteverted nares, retrognathia, abnormal ears,
      laryngeal and cardiac anomalies, brachydactyly, and hypotonia. We describe the
      findings in a Turkish newborn, presumed to be another example of the Toriello
      Carey syndrome, which extends the phenotype of the syndrome.

PMID- 19852431
TI  - Analysis of the SRY gene in a girl with 45,X/46,XY genotype.
AB  - Analysis of the SRY gene in a girl with 45,X/46,XY genotype: We present a Turner
      syndrome patient with a 45, X/46, XY mosaicism. A seven-year-old patient was
      admitted to our laboratory for evaluation of Turner Syndrome. On physical
      examination, short stature, a webbed neck, a broad chest with widely spaced
      nipples, syndactyly on toes, horse shoe kidney and typical findings of aortic
      coarctation were present. The chromosome karyotype of the patient was 45 X/46 XY.
      Molecular analysis of the blood lymphocytes confirmed the presence of the SRY
      gene of the patient. We report here the clinical and cytogenetic findings in a
      patient with an unusual sex chromosome mosaicism.

PMID- 19852432
TI  - Rubinstein-Taybi syndrome and CREBBP c.201 202delTA mutation: a case presenting
      with varicella meningoencephalitis.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare syndrome with a frequency of
      approximately 1 in 125,000 affected newborns, which is characterized by mental
      retardation, growth retardation, a particular dysmorphology and, in a subset of
      cases, immunodeficiency. RTS is typically caused by CREBBP deficiency, and
      heterozygous mutation or deletion of the CREBBP gene has been identified in 60
      70% of patients. The inheritance is autosomal dominant but reports of vertical
      transmission are exceedingly rare; near-all cases are caused by de novo
      mutations. Here we present an 8-month-old boy with varicella meningoencephalitis,
      RTS, and a de novo deletion of the CREBBP gene of two base pairs at position 201
      202 in exon 2, c. 201 202delT. The mutation has not been described previously but
      it predicts a protein truncation, and truncating CREBBP mutations are typical
      causes of RTS.

PMID- 19852433
TI  - A Feingold syndrome case with previously undescribed features and a new mutation.
AB  - Feingold syndrome (FS) is a dominantly inherited combination of microcephaly with
      or without learning disabilities, hand and foot abnormalities, short palpebral
      fissures and esophageal/duodenal atresia. The syndrome has autosomal dominant
      inheritance with full penetrance, and variable expressivity. Digital anomalies
      are almost always present. The gene for FS is localized to a 2.2 cM region in
      2p23-p24. We report on the first Turkish family with Feingold syndrome. The
      propositus is a male infant with microcephaly, frontal balding,
      brachymesophalangy of the second and fifth fingers, bilateral syndactyly of toes
      2-3, facial anomalies, choanal atresia and focal epilepsy. His father has
      microcephaly, and more severe hands and feet abnormalities. One of his brothers
      died because of eosofageal atresia. Clinical presentation of the family was
      suggestive of Feingold syndrome, and genetic testing of the MYCN gene confirmed
      the diagnosis. The missense mutation we report here has not been described
      previously. FS is an autosomal dominant condition, and therefore, the diagnosis
      has important implications for genetic counseling.

PMID- 19852434
TI  - Down syndrome associated with severe combined immunodeficiency: a case report.
AB  - An 8-month-old boy was admitted to the hospital because of recurrent
      bronchopneumonia and gastrointestinal tract infections. On physical examination,
      he had hypotonia, mental retardation, microcephaly with flat facies, low nasal
      bridge, small nose, small ears. Laboratory evaluation revealed Down syndrome,
      lymphopenia, hypogammaglobulinemia, reduced proportions of the peripheral blood
      lymphocytes with an inverted CD4/CD8 ratio and markedly reduced mitogen response
      of the lymphocytes. We report here unique case of Down syndrome associated with
      severe combined immunodeficiency.

PMID- 19852435
TI  - Hyperekplexia in a neonate: a novel finding in Fukuyama type congenital muscular
      dystrophy.
AB  - The Fukuyama type congenital muscular dystrophy (FCMD) is a rare autosomal
      recessive disorder characterized by cranial, cerebellar and ocular malformations
      and congenital muscular dystrophy. Hyperekplexia is characterized by transient,
      generalized rigidity in response to unexpected loud noises or sudden tactile
      stimulation. Herein, we report an infant who had typical clinical features of
      FCMD with hyperekplexia. Our purpose is to draw attention to this first report of
      concomitant FCMD and hyperekplexia.

PMID- 19852436
TI  - Prenatal diagnosis of partial trisomy 14q (14q31.1-->qter) and partial monosomy
      5p (5p13.2-->pter) associated with polyhydramnios, short limbs, micropenis and
      brain malformations.

PMID- 19852437
TI  - Joubert syndrome associated with patent ductus arteriosus in a newborn infant.

PMID- 19852438
TI  - Elastic moduli of cellulose nanoparticle-reinforced composites: a micromechanical
      model.
AB  - A model for the elastic coefficients of fiber-reinforced materials is applied
      toward the analysis of the tensile and shear moduli of nanocomposites reinforced
      by rod-like cellulose nanoparticles. Our formalism integrates results from
      percolation theory with micromechanical and effective medium approaches.
      Polydispersity in the fiber length distribution and anisotropies in the stiffness
      coefficients of cellulose nanoparticles are taken into account explicitly.
      Results from calculations employing our model display reasonable agreement with
      experimental measurements of the moduli as functions of the filler volume
      fraction for several cellulose nanoparticle-reinforced thermoplastic-based
      composites.

PMID- 19852439
TI  - Improving virtual screening performance against conformational variations of
      receptors by shape matching with ligand binding pocket.
AB  - In this report, we present a novel virtual high-throughput screening methodology
      to assist in computer-aided drug discovery. Our method, designated as SLIM,
      involves ligand-free shape and chemical feature matching. The procedure takes
      advantage of a negative image of a binding pocket in a target receptor. The
      negative image is a set of virtual atoms representing the inner shape and
      chemical features of the binding pocket. Using this image, SLIM implements a
      shape-based similarity search based on molecular volume superposition for the
      ensemble of conformers of each molecule. The superposed structures, prioritized
      by shape similarity, are subjected to comparison of chemical feature
      similarities. To validate the merits of the SLIM method, we compared its
      performance with those of three distinct widely used tools ROCS, GLIDE, and GOLD.
      ROCS was selected as a representative of the ligand-centric methods, and docking
      programs GLIDE and GOLD as representatives of the receptor-centric methods. Our
      data suggest that SLIM has overall hit ranking ability that is comparable to that
      of the docking method, retaining the high computational speed of the ligand
      centric method. It is notable that the SLIM method offers consistently reliable
      screening quality against conformational variations of receptors, whereas the
      docking methods have limited screening performance.

PMID- 19852440
TI  - Stereostructure and biological activity of 42-hydroxy-palytoxin: a new palytoxin
      analogue from Hawaiian Palythoa subspecies.
AB  - This paper reports on the analysis of the toxin content from Palythoa tuberculosa
      and Palythoa toxica samples collected off of the Hawaiian coast. Our work, based
      on in-depth high-resolution liquid chromatography-mass spectrometry analysis
      along with extensive NMR study, led us to structurally characterize 42-hydroxy
      palytoxin, a new palytoxin congener. This toxin and palytoxin itself appeared to
      be the major components of toxic extract from a P. tuberculosa sample, while 42
      hydroxy-palytoxin was proven by far to be the main palytoxin derivative in P.
      toxica. Functional studies on this new palytoxin-like compound suggest that the
      new palytoxin analogue and palytoxin itself present similar biological
      activities.

PMID- 19852441
TI  - Colorimetric assay for lead ions based on the leaching of gold nanoparticles.
AB  - A colorimetric, label-free, and nonaggregation-based gold nanoparticles (Au NPs)
      probe has been developed for the detection of Pb(2+) in aqueous solution, based
      on the fact that Pb(2+) ions accelerate the leaching rate of Au NPs by
      thiosulfate (S(2)O(3)(2-)) and 2-mercaptoethanol (2-ME). Au NPs reacted with
      S(2)O(3)(2-) ions in solution to form Au(S(2)O(3))(2)(3-) complexes on the Au NP
      surfaces, leading to slight decreases in their surface plasmon resonance (SPR)
      absorption. Surface-assisted laser desorption/ionization time-of-flight
      ionization mass spectrometry (SALDI-TOF MS) data reveals the formation of Pb-Au
      alloys on the surfaces of the Au NPs in the presence of Pb(2+) ions and 2-ME. The
      formation of Pb-Au alloys accelerated the Au NPs rapidly dissolved into solution,
      leading to dramatic decreases in the SPR absorption. The 2-ME/S(2)O(3)(2-)-Au NP
      probe is highly sensitive (LOD = 0.5 nM) and selective (by at least 1000-fold
      over other metal ions) toward Pb(2+) ions, with a linear detection range (2.5 nM
      10 muM) over nearly 4 orders of magnitude. The cost-effective probe allows rapid
      and simple determination of the concentrations of Pb(2+) ions in environmental
      samples (Montana soil and river), with results showing its great practicality for
      the detection of lead in real samples.

PMID- 19852442
TI  - Diversity-oriented synthesis of angular bis-benzimidazole derivatives under
      microwave irradiation.
AB  - Pharmaceutically interesting, angular bis-benzimidazoles with three appendages
      have been synthesized successfully through a diversity-oriented approach with
      soluble support under microwave irradiation. Polymer immobilized o
      phenylenediamine was selectively N-acylated with 2-chloro-3-nitrobenzoic acid in
      a primary aromatic amino moiety. The obtained amide was cyclized to benzimidazole
      in an acidic condition, and subsequently nucleophilic aromatic substitution with
      different amines was performed. Successive reduction, cyclization with various
      aldehydes and activated isothiocyanates yielded angular biheterocyclic
      benzimidazoles in good quantities. Reaction progress on polymer support was
      precisely monitored using the conventional proton NMR spectroscopy. Preliminary
      screening results showed some of these interesting compounds exhibited moderately
      to good inhibition against vascular endothelial growth factor receptor 3 (VEGFR
      3), which is related to invasion and migration of cancer cells.

PMID- 19852443
TI  - High-k organic, inorganic, and hybrid dielectrics for low-voltage organic field
      effect transistors.

PMID- 19852445
TI  - Endohedral cluster of Li(10)O with T(d) symmetry.
AB  - A detailed numerical study of several isomers of the Li(10) cluster has been
      done. The analysis of the electronic localization function and the analysis of
      energy diagrams revealed the existence of one cluster with an inner space capable
      to suit a heteroatom. The perfect candidate is the Li(10)O cluster due to the
      experimental evidence of the [Li(6)O](4+) core, the same core present in Li(10)O.
      In order to check the thermodynamic stability of this cluster, an analysis of its
      dissociation channels has been done. The IR and UV-vis spectra have been
      calculated to help in the further identification of this new cluster.

PMID- 19852446
TI  - Double-channel photoionization followed by geminate charge
      recombination/separation.
AB  - The photoionization of perylene by tetracyanoethylene (TCNE) in liquid solutions
      is reconsidered within the corrected energy scheme for a double channel electron
      transfer: to the ground and excited states of the produced ion pair. The complex
      space dependence of a total (double channel) rate of multiphonon transfer is
      specified and compared to the recently proposed monoexponential model. The
      fitting of the forward electron transfer (ionization) is essentially improved,
      and the real electron coupling and tunneling parameters are firmly established.
      The same has been done for the geminate recombination/separation kinetics,
      accounting theoretically for the hot recombination experienced by 2/3 of the
      initially produced ion pairs. Only 1/3 of them is left for subsequent thermal
      recombination and even less are left for their separation into free ions. The
      yields of the latter, strongly dependent on the initial concentration of TCNE,
      are brought into reasonable coincidence with the theoretical predictions by a
      renormalization of the empirically calibrated ion densities especially at large
      concentrations. Altogether, this is a precedent spin-less treatment of
      photoionization well-fitted to the experimental data at all times (from the
      excitation until charge separation), with a single set of varying parameters.

PMID- 19852447
TI  - Chlorine-catalyzed ozone destruction: Cl atom production from ClOOCl photolysis.
AB  - Recent laboratory measurements of the absorption cross sections of the ClO dimer,
      ClOOCl, have called into question the validity of the mechanism that describes
      the catalytic removal of ozone by chlorine. Here we describe direct measurements
      of the rate-determining step of that mechanism, the production of Cl atoms from
      the photolysis of ClOOCl, under laboratory conditions similar to those in the
      stratosphere. ClOOCl is formed in a cold-temperature flowing system, with
      production initiated by a microwave discharge of Cl(2) or photolysis of
      CF(2)Cl(2). Excimer lasers operating at 248, 308, and 352 nm photodissociate
      ClOOCl, and the Cl atoms produced are detected with time-resolved atomic
      resonance fluorescence. Cl(2), the primary contaminant, is measured directly for
      the first time in a ClOOCl cross section experiment. We find the product of the
      quantum yield of the Cl atom production channel of ClOOCl photolysis and the
      ClOOCl absorption cross section, (phisigma)(ClOOCl) = 660 +/- 100 at 248 nm, 39.3
      +/- 4.9 at 308 nm, and 8.6 +/- 1.2 at 352 nm (units of 10(-20) cm(2) molecule(
      1)). The data set includes 468 total cross section measurements over a wide range
      of experimental conditions, significantly reducing the possibility of a
      systematic error impacting the results. These new measurements demonstrate that
      long-wavelength photons (lambda = 352 nm) are absorbed by ClOOCl directly,
      producing Cl atoms with a probability commensurate with the observed rate of
      ozone destruction in the atmosphere.

PMID- 19852448
TI  - Structures and energetics of H(6)(+) clusters.
AB  - Theoretical investigations of the equilibrium structures and associated
      isomerization reactions of the hydrogen clusters H(6)(+) have been carried out.
      Three equilibrium structures and three isomerization transition states were
      located on the electronic doublet and quartet states of the respective potential
      energy surfaces. The research employed ab initio self-consistent-field (SCF),
      coupled cluster (CC) with single and double excitations (CCSD), CCSD with
      perturbative triple excitations (CCSD(T)), and full triple excitations (CCSDT)
      wave functions and a wide variety of correlation-consistent polarized valence cc
      pVXZ and aug-cc-pVXZ (where X = D, T, Q) basis sets. For each structure the
      geometry, energy, dipole moment, harmonic vibrational frequencies, and infrared
      intensities are predicted. Complete active space SCF (CASSCF) and multireference
      configuration interaction (MRCI) wave functions are used to analyze the effect of
      correlation on physical properties and energetics. Extensive focal point analyses
      (including CCSDTQ and full CI energies and basis sets up to sextuple zeta) are
      used to obtain complete basis set (CBS) limit energies. The H(2)(+)-core H(6)(+)
      cluster with D(2d) symmetry is the global minimum, lying 3.9 (4.2) +/- 0.1 kcal
      mol(-1) below the H(3)(+)-core H(6)(+) cluster with C(s) symmetry, where zero
      point vibrational energy (ZPVE) corrected value are shown in parentheses. The
      barrier of the isomerization reaction between these two structures is 7.4 (5.2)
      +/- 0.1 kcal mol(-1). The dissociation energies for the H(2)(+)-core H(6)(+)
      isomer [H(6)(+) (D(2d)) --> 2H(2) + H(2)(+)] and the H(3)(+)-core H(6)(+) isomer
      [H(6)(+) (C(s)) --> H(3)(+) + H(2) + H] are 57.5 (50.9) +/- 0.1 and 12.3 (8.3) +/
      0.1 kcal mol(-1), respectively.

PMID- 19852449
TI  - Spectroscopic and theoretical study of the "azo"-dye E124 in condensate phase:
      evidence of a dominant hydrazo form.
AB  - Spectroscopic techniques, including Raman, IR, UV/vis, and NMR were used to
      characterize the samples of the azo dye Ponceau 4R (also known as E124, New
      Coccine; Cochineal Red; C.I. no. 16255; Food Red No. 102), which is 1,3
      naphthalenedisulfonic acid, 7-hydroxy-8-[(4-sulfo-1-naphthalenyl) azo] trisodium
      salt in aqueous solution and solid state. In addition, first principle
      calculations were carried out for the azo (OH) and hydrazo (NH) tautomers in
      order to assist in the assignment of the experimental data. The two intense bands
      observed in the UV/vis spectrum, centered at 332 and 507 nm, can be compared to
      the calculated values at 296 and 474 nm for azo and 315 and 500 nm for hydrazo
      isomer, with the latter in closer agreement to the experiment. The Raman spectrum
      is quite sensitive to tautomeric equilibrium; in solid state and aqueous
      solution, three bands were observed around 1574, 1515, and 1364 cm(-1), assigned
      to mixed modes including deltaNH + betaCH + nuCC, deltaNH + nuC horizontal lineO
      + nuC horizontal lineN + betaCH and nuCC vibrations, respectively. These
      assignments are predicted only for the NH species centered at 1606, 1554, and
      1375 cm(-1). The calculated Raman spectrum for the azo (OH) tautomer showed two
      strong bands at 1468 (nuN = N + deltaOH) and 1324 cm(-1) (nuCC + nuC-N), which
      were not obtained experimentally. The (13)C NMR spectrum showed a very
      characteristic peak at 192 ppm assigned to the carbon bound to oxygen in the
      naphthol ring; the predicted values were 165 ppm for OH and 187 for NH isomer,
      supporting once again the predominance of NH species in solution. Therefore, all
      of the experimental and theoretical results strongly suggest the food dye Ponceau
      4R or E124 has a major contribution of the hydrazo structure instead of the azo
      form as the most abundant in condensate phase.

PMID- 19852450
TI  - Molecular dynamics investigation of the bimolecular reaction BeH + H(2) -->
      BeH(2) + H on an ab initio potential-energy surface obtained using neural network
      methods with both potential and gradient accuracy determination.
AB  - The classical reaction dynamics of a four-body, bimolecular reaction on a neural
      network (NN) potential-energy surface (PES) fitted to a database obtained solely
      from ab initio MP2/6-311G(d,p) calculations are reported. The present work
      represents the first reported application of ab initio NN methods to a four-body,
      bimolecular, gas-phase reaction where bond extensions reach 8.1 A for the BeH +
      H(2) --> BeH(2) + H reaction. A modified, iterative novelty sampling method is
      used to select data points based on classical trajectories computed on temporary
      NN surfaces. After seven iterations, the sampling process is found to converge
      after selecting 9604 configurations. Incorporation of symmetry increases this to
      19 208 BeH(3) configurations. The analytic PES for the system is obtained from
      the ensemble average of a five-member (6-60-1) NN committee. The mean absolute
      error (MAE) for the committee is 0.0046 eV (0.44 kJ mol(-1)). The total energy
      range of the BeH(3) database is 147.0 kJ mol(-1). Therefore, this MAE represents
      a percent energy error of 0.30%. Since it is the gradient of the PES that
      constitutes the most important quantity in molecular dynamics simulations, the
      paper also reports mean absolute error for the gradient. This result is 0.026 eV
      A(-1) (2.51 kJ mol(-1) A(-1)). Since the gradient magnitudes span a range of
      15.32 eV A(-1) over the configuration space tested, this mean absolute gradient
      error represents a percent error of 0.17%. The mean percent absolute relative
      gradient error is 4.67%. The classically computed reaction cross sections
      generally increase with total energy. They vary from 0.007 to 0.030 A(2) when
      H(2) is at ground state, and from 0.05 to 0.10 A(2) when H(2) is in the first
      excited state. Trajectory integration is very fast using the five-member NN PES.
      The average trajectory integration time is 1.07 s on a CPU with a clock speed of
      2.4 GHz. Zero angular momentum collisions are also investigated and compared with
      previously reported quantum dynamics on the same system. The quantum reaction
      probabilities exhibit pronounced resonance effects that are absent in the
      classical calculations. The magnitudes of quantum and classical results are in
      fair accord with the classical results being about 30-40% higher due to the lack
      of quantum restrictions on the zero-point vibrational energy.

PMID- 19852451
TI  - Thermodynamic properties of hyperbranched polymer, Boltorn U3000, using inverse
      gas chromatography.
AB  - Mass-fraction activity coefficients at infinite dilution (Omega13(infinity)) of
      alkanes (C5-C10), cycloalkanes (C5-C8), alkenes (C5-C8), alkynes (C5-C8),
      aromatic hydrocarbons (benzene, toluene, ethylbenzene, o-, m-, p-xylene,
      thiophene), alcohols (C1-C5), water, ethers (tetrahydrofuran (THF), methyl-tert
      butylether (MTBE), diethyl-, di-n-propyl-, di-n-butyl ether), and ketones
      (propanone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, cyclopentanone) in
      the hyperbranched polymer, Boltorn U3000 (B-U3000), have been determined by
      inverse gas chromatography (IGC) using the polymer as the stationary phase. The
      measurements were carried out at different temperatures between 308.15 and 348.15
      K. The density and thermophysical properties of polymer were described. The
      specific retention volume (V(g)), the Flory-Huggins interaction parameter
      (chi13(infinity)), the molar enthalpy of sorption (the partial molar enthalpies
      of solute dissolution) (Delta(s)H), the partial molar excess enthalpy at infinite
      dilution of the solute and polymer (DeltaH1(E,infinity)), the partial molar Gibbs
      excess energy at infinite dilution (DeltaG1(E,infinity)), and the solubility
      parameter (delta3) were calculated.

PMID- 19852452
TI  - Short-range structure of invert glasses along the pseudo-binary join MgSiO3
      Mg2SiO4: results from 29Si and 25Mg MAS NMR spectroscopy.
AB  - The short-range structure of "invert" glasses along the pseudobinary join
      MgSiO(3)-Mg(2)SiO(4) has been studied using (29)Si and (25)Mg MAS NMR
      spectroscopy. The results indicate a progressive compositional evolution in Q
      speciation that approximately follows a statistical distribution. The Mg(2)SiO(4)
      glass shows an abrupt deviation from this trend with the presence of nearly 40%
      of the Si atoms as (Si(2)O(7))(6-) dimers, i.e., Q(1) species. Mg(2+) ions are
      present in predominantly octahedral coordination in all glasses. When taken
      together, these results indicate that glasses with MgO contents between 50 and 60
      mol % are characterized by a structure consisting primarily of at least three
      types of Q species and MgO(6) octahedra. On the other hand, the structure of
      glasses with >60 mol % MgO appears to consist of Q(0) and Q(1) species with
      structural connectivity being primarily provided by the MgO(6) octahedra. The
      possible consequences of such compositional evolution of structure on the ability
      of glass formation in this system are discussed.

PMID- 19852453
TI  - Ligand migration between internal docking sites in photodissociated carbonmonoxy
      neuroglobin.
AB  - Neuroglobin (Ngb) belongs to the large family of globular heme proteins capable
      of binding small gaseous ligands such as O(2), CO, or NO within their active
      site. In this work, we have analyzed CO migration pathways in photolyzed NgbCO
      using molecular dynamics (MD) simulations in combination with Fourier transform
      infrared temperature derivative spectroscopy (FTIR-TDS). A total of 55 ns of MD
      simulation was analyzed to explore the approximately 300 A(3) internal Ngb
      cavity. Overall, the simulations differentiated between eight possible docking
      sites, three of which were also identified experimentally. Low-temperature FTIR
      TDS experiments on wild-type (wt) and F28W mutant NgbCO revealed that a small
      fraction of ligands migrates from site B to site C from which they rebound after
      slow cool illumination. For the F28L mutant, however, population of site C was
      not observed. In agreement with these findings, the simulations at 20 K showed
      ligand transfer between sites B and C for wt Ngb, but not for the F28L mutant.
      The ligand migration network could be mapped out and two key gate residues, Phe28
      and Pro52, were identified. Ligand population analysis from the MD simulations
      revealed a direct relation between the size of the B10 side chain (Phe28 in wild
      type Ngb) and the barrier against migration. Barriers for the transition of
      photodissociated CO from the distal pocket to the Xe4 site in Ngb are lower by up
      to 4 kcal/mol compared to myoglobin, suggesting that ligand migration between
      different docking sites is more facile in Ngb than in myoglobin.

PMID- 19852454
TI  - Unexpected hydrogen bond dynamics in imidazolium-based ionic liquids.
AB  - Employing first-principles molecular dynamics simulations, we characterize the
      structural and dynamical hydrogen bonding in the ionic liquid [C(2)C(1)im][SCN].
      The geometric picture indicates a superior role for the most acidic hydrogen bond
      (at H2) as compared to the two other hydrogen atoms at the rear. Despite the
      structural picture, the hydrogen bond dynamics at H2 is found to decay faster
      than the according dynamics at the H4 and H5 proton. Neglecting the
      directionality provides a dynamics which reflects the geometrical analysis. Two
      movements are identified. First, a fast (<0.3 ps) hopping of the anion above and
      below the imidazolium ring and second translational motion of the anion away from
      the cation in-plane of the imidazolium ring (5-10 ps).

PMID- 19852455
TI  - Role of the range in the fluid-crystal coexistence for a patchy particle model.
AB  - We evaluate the phase diagram of the four-site Kern-Frenkel patchy particle model
      [Kern, N.; Frenkel, D. J. Chem. Phys. 2003, 118, 9882.], a model representative
      of particles interacting via short-range orientational interactions, for several
      values of the interaction range. Similar to what has been found for isotropic
      potentials, the liquid phase disappears as an equilibrium phase for values of the
      range on the order of 15% of the particle diameter. For smaller ranges, the gas
      liquid phase separation becomes metastable with respect to crystallization into a
      diamond-like structure. Interestingly, and differently from the isotropic case,
      the supersaturation of the fluid at the critical point does not significantly
      increase upon going toward the adhesive (vanishing interaction range) limit.

PMID- 19852456
TI  - Deprotonation and oligomerization in photo-, radiolytically, and
      electrochemically induced redox reactions in hydrophobic alkylalkylimidazolium
      ionic liquids.
AB  - Radical chemistry initiated by one-electron reduction of 1-methyl-3
      alkylimidazolium cations in the corresponding ionic liquids (ILs) is examined.
      The reaction scheme is examined in light of the recent experimental data on photo
      , radiation-, and electrochemically induced degradation of the practically
      important hydrophobic alkylimidazolium ILs. It is suggested that the primary
      species leading to the formation of the oligomers and acidification of the IL is
      a sigmasigma* dimer radical cation that loses a proton, yielding a neutral
      radical whose subsequent reactions produce C(2)-C(2) linked oligomers, both
      neutral and charged. The neutral oligomers (up to the tetramer) account for the
      features observed in the NMR spectra of cathodic liquid generated in electrolytic
      breakdown of the IL solvent. In photolysis and radiolysis, these neutral species
      and/or their radical precursors are oxidized by radical (ions) derived from the
      counteranions, and only charged dimers are observed. The dication dimers account
      for the features observed in the mass spectra of irradiated ILs. The products of
      these ion radical and radical reactions closely resemble those generated via
      carbene chemistry, without the formation of the carbene via the deprotonation of
      the parent cation. As the loss of 2-protons increases the proticity of the
      irradiated IL, it interferes with the extraction of metal ions by ionophore
      solutes, while the formation of the oligomers modifies solvent properties. Thus,
      the peculiarities of radical chemistry in the alkylimidazolium ILs have
      significant import for their practical applications.

PMID- 19852457
TI  - Surface and catalytic elucidation of Rh/gamma-Al2O3 catalysts during NO reduction
      by C3H8 in the presence of excess O2, H2O, and SO2.
AB  - The present study aims at exploring the surface and catalytic behavior of
      Rh/gamma-Al(2)O(3) catalysts during the selective reduction of NO by C(3)H(8) in
      the presence of excess oxygen, H(2)O, and SO(2) with particular emphasis on
      identifying the elementary steps that describe the reaction mechanism. To this
      end, detailed activity and stability tests were employed and a precise kinetic
      analysis was carried out at differential conditions to elucidate the effect of
      each reactant, including H(2)O and SO(2), on the total reaction rate. At the same
      time, temperature programmed desorption (TPD) studies in combination with in situ
      diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy were carried
      out under various reaction conditions to correlate the catalytic performance of
      Rh/gamma-Al(2)O(3) catalyst with its corresponding surface chemistry. The results
      reveal that in the absence of H(2)O and SO(2), the reaction follows a typical
      "reduction" type mechanism, where the active intermediates (NO(X), carboxylates,
      isocyanates) are interacting to yield the final products. In this reaction
      sequence the formation of carboxylate (C(x)H(y)O(z)) species is considered as the
      rate determining step. Water affects in a different way the NO and C(3)H(8)
      conversion performance of Rh/gamma-Al(2)O(3) catalyst; its effect is totally
      reversible in the case of C(3)H(8) oxidation, while the NO reduction was
      permanently affected mainly due to the oxidation of Rh active sites. In contrast,
      SO(2) poisons both reactions irreversibly via the formation of strongly adsorbed
      sulfate compounds, which hinder the adsorption and consequently the activation of
      reactants.

PMID- 19852458
TI  - Efficient synthesis of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate: a
      versatile precursor to o-benzyne.
AB  - An efficient procedure for the gram-scale preparation of 2-(trimethylsilyl)phenyl
      trifluoromethanesulfonate, a versatile precursor to o-benzyne, is presented. The
      three-step sequence utilizes phenol as the starting material, requires only one
      chromatographic purification, and ultimately delivers the desired silyltriflate
      in 66% overall yield.

PMID- 19852459
TI  - Stereoselective synthesis of the C31-C40/C43-C52 unit of amphidinol 3.
AB  - A concise synthesis of a tetrahydropyran ring system corresponding to the C31-C40
      and C43-C52 units of amphidinol 3 is described. Successive chemoselective
      reactions, i.e., cross-metathesis to differentiate the iodoolefin from the
      terminal olefin and Sharpless asymmetric dihydroxylation on the resulting E
      olefin, resulted in expeditious synthesis of an intermediate that was then cross
      coupled to afford an E,E-diene system. Four contiguous stereogenic centers were
      installed via construction of the tetrahydropyran ring by means of Katsuki
      Sharpless asymmetric epoxidation, 6-endo-tet cyclization, and Sharpless
      asymmetric dihydroxylation.

PMID- 19852460
TI  - Synthesis of gamma-butyrolactams by photoinduced PhSe group transfer radical
      cyclization and formal synthesis of (+/-)-isocynometrine with diphenyldiselenide
      as promoter.
AB  - We have developed a strategy for constructing nitrogen heterocycles by
      photoinduced PhSe group transfer radical cyclization. trans-Alpha,beta
      disubstituted gamma-butyrolactams (2-pyrrolidinones) were prepared in good yields
      (38-73%) with high regioselectivity and stereoselectivity from N-alkenyl alpha
      PhSe beta-keto amides. Reaction outcomes were modulated by the steric effect of
      the substituents on the nitrogen atom of the cyclization precursors and the
      stereoelectronic effect of the substrates. Diphenyldiselenide, as an additive,
      was found to promote ring closure. The advantage of this strategy in natural
      product synthesis is demonstrated by a formal synthesis of (+/-)-isocynometrine.

PMID- 19852461
TI  - Hydrogen storage in high surface area carbons: experimental demonstration of the
      effects of nitrogen doping.
AB  - The influence of nitrogen doping on the hydrogen uptake and storage capacity of
      high surface area carbon materials is presented in this report. To generate
      suitable study materials, we have exploited the relationship between synthesis
      conditions and textural properties of zeolite-templated carbons to generate a
      range of high surface area carbons with similar pore size distribution but which
      are either N-doped or N-free. For N-doped carbons, the nitrogen content was kept
      within a narrow range of between 4.7 and 7.7 wt %. The carbon materials,
      irrespective of whether they were doped or not, exhibited high surface area (1900
      3700 m(2)/g) and pore volume (0.99 and 1.88 cm(3)/g), a micropore surface area of
      1500-2800 m(2)/g, and a micropore volume of 0.65-1.24 cm(3)/g. The hydrogen
      uptake varied between 4.1 and 6.9 wt %. We present experimental data that
      indicates that the effect of N-doping on hydrogen uptake is only apparent when
      related to the surface area and pore volume associated with micropores rather
      than total porosity. Furthermore, by considering the isosteric heat of hydrogen
      adsorption and excess hydrogen uptake on N-free or N-doped carbons, it is shown
      that N-doping can be beneficial at lower coverage (low hydrogen uptake) but is
      detrimental at higher coverage (higher hydrogen uptake). The findings are
      consistent with previous theoretical predictions on the effect of N-doping of
      carbon on hydrogen uptake. The findings, therefore, add new insights that are
      useful for the development of carbon materials with enhanced hydrogen storage
      capacity.

PMID- 19852463
TI  - Anionic surfactant with hydrophobic and hydrophilic chains for nanoparticle
      dispersion and shape memory polymer nanocomposites.
AB  - An anionic surfactant comprising a hydrophilic poly(ethylene glycol) (PEG) chain,
      hydrophobic alkyl chain, and polymerizable vinyl group was synthesized as a
      capping agent of nanoparticles. TiO(2) nanoparticles modified by this surfactant
      were completely dispersible in various organic solvents with a wide range of
      polarities, such as nitriles, alcohols, ketones, and acetates. Furthermore, these
      particles were found to be dispersible in various polymers with different
      properties, such as thermosetting epoxy resins and radical polymerized
      poly(methylmethacrylate) (PMMA). A polymer composite of surface-modified TiO(2)
      nanoparticles in epoxy resins prepared by using the developed surfactant also
      possessed temperature-induced shape memory properties.

PMID- 19852462
TI  - C-H bond functionalization via hydride transfer: direct coupling of unactivated
      alkynes and sp(3) C-H bonds catalyzed by platinum tetraiodide.
AB  - We report a catalytic intramolecular coupling between terminal unactivated
      alkynes and sp(3) C-H bonds via through-space hydride transfer (HT-cyclization of
      alkynes). This method enables one-step preparation of complex heterocyclic
      compounds by alpha-alkenylation of readily available cyclic ethers and amines. We
      show that PtI(4) is an effective Lewis acid catalyst for the activation of
      terminal alkynes for hydride attack and subsequent C-C bond formation. In
      addition, we have shown that the activity of neutral platinum salts (PtX(n)) can
      be modulated by the halide ligands. This modulation in turn allows for fine
      tuning of the platinum center reactivity to match the reactivity and stability of
      selected substrates and products.

PMID- 19852466
TI  - Nanodroplet activated and guided folding of graphene nanostructures.
AB  - We demonstrate by molecular dynamics simulations that water nanodroplets can
      activate and guide the folding of planar graphene nanostructures. Once the
      nanodroplets are deposited at selected spots on the planar nanostructure, they
      can act as catalytic elements that initiate conformational changes and help to
      overcome deformation barriers associated with them. Nanodroplets can induce rapid
      bending, folding, sliding, rolling, and zipping of the planar nanostructures,
      which can lead to the assembly of nanoscale sandwiches, capsules, knots, and
      rings.

PMID- 19852465
TI  - Functional neoglycopeptides: synthesis and characterization of a new class of
      MUC1 glycoprotein models having core 2-based O-glycan and complex-type N-glycan
      chains.
AB  - An efficient protocol for the construction of MUC1-related glycopeptide analogues
      having complex O-glycan and N-glycan chains was established by integrating
      chemical and enzymatic approaches on the functional polymer platforms. We
      demonstrated the feasibility of sortase A-mediated ligation between two
      glycopeptide segments by tagging with signal peptides, LPKTGLR and GG, at each C-
      or N-terminal position. Structural analysis of the macromolecular N,O
      glycopeptides was performed by means of ESI-TOFMS (MS/MS) equipped with an
      electron-captured dissociation device. Immunological assay using MUC1
      glycopeptides synthesized in this study revealed that N-glycosylation near the
      antigenic O-glycosylated PDTR motif did not disturb the interaction between the
      anti-MUC1 monoclonal antibody and this crucial O-glycopeptide moiety. NMR study
      indicated that the N-terminal immunodominant region [Ala-Pro-Asp-Thr(O-glycan)
      Arg] forms an inverse gamma-turn-like structure, while the C-terminal region
      composed of N-glycopeptide and linker SrtA-peptide was proved to be an
      independently random structure. These results indicate that the bulky O- and N
      glycan chains can function independently as disease-relevant epitopes and ligands
      for carbohydrate-binding proteins, when both are combined by an artificial
      intervening peptide having a possible effect of separating N- and C-terminal
      regions. The present strategy will greatly facilitate rapid synthesis of multiply
      functionalized complex neoglycopeptides as new types of convenient tools or
      models for the investigation of thhe structure-function relationship of various
      glycoproteins and development of novel class glycopeptide-based
      biopharmaceuticals, drug delivery systems, and biomedical materials.

PMID- 19852467
TI  - Fluorescence of 5-arylvinyl-5'-methyl-2,2'-bipyridyl ligands and their zinc
      complexes.
AB  - The photophysical properties of 5-arylvinyl-5'-methyl-2,2'-bipyridyls (AVMBs, 1
      9, 11) and their zinc complexes were studied. Similar 2,2'-bipyridyl-based
      ligands have been applied as optical sensors for metal ions and sensitizers for
      solar energy conversion. The goal of this investigation is to reveal the factors
      that determine the emission band shift and fluorescence quantum yield change of
      the title ligand system upon zinc binding. The outcome of this study will not
      only advance the fundamental understanding of the coordination-driven
      photophysical processes embodied in the AVMB platform but facilitate the rational
      design of fluorescent probes for metal ions, particularly zinc. The AVMB ligands
      were synthesized using the Horner-Wadsworth-Emmons reaction. AVMBs containing
      electron-donating aryl groups show absorption and emission in the visible region,
      which can be assigned to charge-transfer transitions as supported by solvent
      dependency and computational studies. The binding between AVMB ligands and zinc
      ion in acetonitrile was studied using isothermal titration calorimetry (ITC). A
      multicomponent equilibrium model is suggested that explains the multiple
      transitions evidenced in fluorescence titration isotherms. Coordination to zinc
      ion stabilizes the charge-transfer excited state of an AVMB ligand with an
      electron-donating aryl substituent, consequently results in bathochromic shifts
      in both absorption and emission. However, unlike the emission band shift, the
      fluorescence quantum yield change upon zinc complex formation does not have an
      intuitive correlation with the electronic nature of the aryl group. Lifetime
      measurements using the Time-Correlated Single Photon Counting method enabled the
      determination of nonradiative and radiative decay rate constants. Both rates of
      an AVMB ligand decrease upon zinc binding. The collective effect gives rise to
      the change in fluorescence quantum yield with the apparent lack of correlation
      with the electronic property of the aryl group.

PMID- 19852468
TI  - Synthesis of 3-alkoxymethylcoumarin from 3-cyanochromene via a novel intermediate
      2-phenylimino-3-alkoxymethylchromene.
AB  - In this paper a concise, efficient, and environmentally benign method for the
      synthesis of 3-alkoxymethylcoumarin is described. From the reaction of 3
      cyanochromene with an alkoxide and arylamine in THF, (Z)-2-phenylimino-3
      alkoxymethylchromene was obtained as a novel intermediate via an isomerization of
      the double bond, a 1,2-addition of alkoxide, a Michael-type addition of aniline,
      an another isomerization of double bond and an elimination of ammonia.
      Subsequently, the intermediate was converted into the desired coumarin by
      treatment with 15% HCl in THF in good yield.

PMID- 19852469
TI  - Novel juvenogens (insect hormonogenic agents): preparation and biological tests
      on Neobellieria bullata.
AB  - The development of new types of environmentally safe insecticides has been
      advantageous to replace toxic and persistent insecticides, which have adverse
      effects on animals and humans. Our effort in this field was aimed at the
      synthesis of insect juvenile hormone analogues, juvenoids, nontoxic for warm
      blooded animals and fish, which can become advanced compounds in regulating many
      aspects in insect physiology. Structure modification of juvenoids via juvenogen
      derivatives (hormonogenic substances) plays an important role in controlling the
      juvenoid liberation rate in the insect digestive system and can also play an
      important role in the mode of action toward different arthropod groups, with
      focus on insect pest species. For that reason, juvenoids were esterified with
      hexadecanoic, butanoic, and 3-methylbut-2-enoic acids. A total of 12 new
      compounds with potential insecticidal activity were synthesized and
      characterized, and the results of biological screening tests on blowflies
      Neobellieria (Sarcophaga) bullata were presented. Results of the inhibitory
      activity of the tested compounds on the reproduction of the blowflies were also
      presented.

PMID- 19852470
TI  - A laundry detergent-stable alkaline trypsin from striped seabream (Lithognathus
      mormyrus) viscera: purification and characterization.
AB  - An alkaline trypsin from the intestine of striped seabream (Lithognathus
      mormyrus) was purified and characterized. The enzyme was purified to homogeneity
      by precipitation with ammonium sulfate, Sephadex G-100 gel filtration and CM
      Sephadex cation-exchange chromatography, with a 24.9-fold increase in specific
      activity and 13% recovery. The molecular weight of the purified alkaline trypsin
      was estimated to be 27.5 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and size exclusion chromatography. The purified
      trypsin appeared as a single band on native PAGE. Interestingly, the enzyme was
      highly active over a wide range of pH from 8.0 to 11.0, with an optimum at pH
      10.0 using Nalpha-benzoyl-dl-arginine-p-nitroanilide (BAPNA) as a substrate. The
      relative activities at pH 8.0, 11.0, and 12.0 were 73%, 67% and 50.4%,
      respectively. The enzyme was extremely stable over a broad pH range (5.0-12.0).
      The optimum temperature for enzyme activity was 50 degrees C. The purified enzyme
      was strongly inhibited by soybean trypsin inhibitor (SBTI). In addition, the
      enzyme showed excellent stability toward various surfactants and bleache agents
      and compatibility with some commercial solid and liquid detergents. The trypsin
      kinetic constants, Km and kcat of the enzyme for BAPNA, were 0.29 mM and 1.36 s(
      1), respectively, while the catalytic efficiency kcat/Km was 4.68 s(-1) mM(-1).

PMID- 19852471
TI  - Identification of lead compounds as antagonists of protein Bcl-xL with a
      diversity-oriented multidisciplinary approach.
AB  - We report on the use of a diversity oriented synthesis (DOS) approach that
      resulted in the generation of a set of libraries of compounds presenting novel
      structural cores. These chemical cores have been employed to design potential
      antagonists of the antiapoptotic protein Bcl-x(L) through reiterated steps of
      molecular docking calculations followed by experimental verification of binding.
      Our data suggest that the DOS approach is suitable to generate novel scaffolds,
      which can be employed to target protein-protein interactions.

PMID- 19852472
TI  - A promising drug controlled-release system based on diacetylene/phospholipid
      polymerized vesicles.
AB  - A novel polymerized vesicular carrier loaded with paclitaxel was developed by
      introducing the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid
      (PCDA) into bilayered phospholipid vesicles with the purpose of improving the
      physicochemical stability as well as the controlled-release property of
      liposomes. Dynamic light scattering (DLS) and transmission electron microscopy
      (TEM) results revealed the enhanced stability of PCDA-polymerized vesicles
      against Triton X-100. In particular, alteration in PCDA/phospholipids ratios and
      UV-irradiation time can modulate the cumulative paclitaxel released. For
      instance, vesicles composed of phospholipids only released 98.0 +/- 2.1% of
      paclitaxel within 24 h. Over the same time period, 72.0 +/- 5.8%, 43.9 +/- 6.5%,
      and 20.1 +/- 5.4% of paclitaxel was released from polymerized PCDA/phospholipid
      vesicles at molar ratios of 1:3, 1:1, and 3:1, respectively. Likewise, by
      increasing the UV-irradiation time from 20 to 40 min, the cumulative release of
      paclitaxel from polymerized PCDA/phospholipid vesicles at molar ratio of 1:1
      decreased from 90.5 +/- 3.7% to 37.6 +/- 2.3% over a time period of experimental
      observation of 24 h. The influences of vesicle composition (i.e.,
      PCDA/phospholipids ratio) and UV-irradiation time on the release rates of
      paclitaxel were further examined by finite element (FE) analyzed using Abaqus.
      Our results demonstrate that novel polymerized vesicles capable of regulating the
      release of anticancer drugs such as paclitaxel have been developed.

PMID- 19852473
TI  - DC electrokinetic particle transport in an L-shaped microchannel.
AB  - Electrokinetic transport of particles through an L-shaped microchannel under DC
      electric fields is theoretically and experimentally investigated. The emphasis is
      placed on the direct current (DC) dielectrophoretic (DEP) effect arising from the
      interactions between the induced spatially nonuniform electric field around the
      corner and the dielectric particles. A transient multiphysics model is developed
      in an arbitrary Lagrangian-Eulerian (ALE) framework, which comprises the Navier
      Stokes equations for the fluid flow and the Laplace equation for the electrical
      potential. The predictions of the DEP-induced particle trajectory shift in the L
      shaped microchannel are in quantitative agreement with the obtained experimental
      results. Numerical studies also show that the DEP effect can alter the angular
      velocity and even the direction of the particle's rotation. Further parametric
      studies suggest that the L-shaped microfluidic channel may be utilized to focus
      and separate particles by size via the induced DEP effect.

PMID- 19852474
TI  - Colloidal amphiphile self-assembly particles composed of gadolinium oleate and
      myverol: evaluation as contrast agents for magnetic resonance imaging.
AB  - Gadolinium oleate has been added at various concentrations to a Myverol inverse
      bicontinuous cubic phase forming system, and the potential of these systems as
      magnetic resonance imaging (MRI) contrast agents has been investigated.
      Differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), and
      cryo-transmission electron microscopy (cryo-TEM) measurements on the Gd
      oleate/Myverol systems indicate that Gd oleate is at least partially incorporated
      within the cubic phase of Myverol. However, at Gd oleate concentrations greater
      than 1 wt %, partial phase separation of the system may occur with the formation
      of a Gd-oleate-rich lamellar phase as well as the cubic phase. Bulk Gd
      oleate/Myverol mixtures can be dispersed into stable colloidal dispersions. SAXS
      and cryo-TEM measurements on these dispersions indicate that the presence of Gd
      oleate in the Myverol system prevents the formation of cubosomes from the bulk
      cubic phase. Instead, the dispersion consists of putative Gd-oleate-rich
      nonswelling lamellar nanoparticles as well as colloidal particles lacking ordered
      internal structure. In vitro studies on these dispersions demonstrated that the
      relaxivity of select Gd oleate/Myverol systems is much higher than that of pure
      Gd oleate, exemplifying the promise of this system type for magnetic resonance
      imaging. The highest water proton relaxivities (r(1) = 34.2 mM(-1) s(-1) and r(2)
      = 27.3 mM(-1) s(-1) at 20 MHz and room temperature) were obtained at a Gd oleate
      loading concentration of 1 wt %, with a subsequent decrease in relaxivity with
      increasing Gd oleate concentration. These maximum relaxivities compare favorably
      with the relaxivities for the commercial contrast agent, Magnevist (r(1) = 4.91
      mM(-1) s(-1) and r(2) = 6.26 mM(-1) s(-1) at 20 MHz and room temperature).

PMID- 19852475
TI  - Accurate random coil chemical shifts from an analysis of loop regions in native
      states of proteins.
AB  - We present a method for calculating accurate random coil chemical shift values of
      proteins. These values are obtained by analyzing the relationship between the
      amino acid sequences in flexible loop regions of native states and the
      corresponding experimentally measured chemical shifts. We estimate the errors in
      the random coil chemical shift scales to be 0.31 ppm for (13)C(alpha), 0.37 ppm
      for (13)C(beta), 0.31 ppm for (13)CO, 0.68 ppm for (15)N, 0.09 ppm for (1)H, and
      0.04 ppm for (1)H(alpha).

PMID- 19852476
TI  - Cyclodextrin supramolecular complex as a water-soluble ratiometric sensor for
      ferric ion sensing.
AB  - Heightened concern for human health and environmental protection has stimulated
      active research on the potential impact of transition-metal ions and their toxic
      effects, thus it is very demanding to design transition-metal ion detection
      methods that are cost-effective, rapid, facile, and applicable to the
      environmental and biological milieus. In this study, we demonstrated an
      alternative strategy for constructing a water-soluble FRET-based ratiometric
      sensor for ferric ion detection by forming a supramolecular beta-cyclodextrin/dye
      complex. This water-soluble FRET system consists of a dansyl-linked beta
      cyclodextrin (beta-CD-DNS) and a spirolactam rhodamine-linked adamantane (AD
      SRhB). The dansyl moiety serves as the donor, and the spirolactam-rhodamine B
      derivative (SRhB) was chosen as a sensitive, selective chemosensor for Fe(III)
      ions and a very efficient ring-opening reaction induced by Fe(III) generates the
      long-wavelength rhodamine B fluorophore that can act as the energy acceptor.
      Moreover, the adamantyl (AD) group, which is known for its capability to form
      stable host-guest inclusion complexes with beta-CD derivatives, was covalently
      linked to the spirolactam rhodamine, thus the adamantyl moiety of the ion
      recognition element can be anchored inside the CD cavity. In this way, the donor
      acceptor separation can be kept within the critical Forster distance;
      accordingly, energy transfer can take place from the donor (dansyl) to the
      acceptor (rhodamine derivative/Fe(III) complex), and thus ratiometric detection
      for Fe(III) in an aqueous medium can be fulfilled. This FRET-based supramolecular
      sensor can be readily formed via an inclusion process using the donor part and
      the acceptor part, hence this strategy could afford a robust approach for
      constructing a wide range of FRET-based water-soluble sensing systems simply by
      assembling a specifically predesigned donor-linked CD and acceptor-linked
      adamantane.

PMID- 19852477
TI  - Valency dependence of polymorphism and polyamorphism in DNA-functionalized
      nanoparticles.
AB  - Nanoparticles (NP) functionalized with single-stranded DNA (ssDNA) offer a route
      to custom-designed, self-assembled nanomaterials with potentially unusual
      properties. The bonding selectivity of DNA guarantees one-to-one binding to form
      double-stranded DNA (dsDNA), and an appropriate base sequence results in head-to
      tail binding linking NP into networks. We explore the phase behavior and
      structure of a model for NP functionalized with between 3 and 6 short ssDNA
      through simulations of a coarse-grained molecular model, allowing us to examine
      both the role of the number of attached strands (valency) and their relative
      orientations. The NP assemble into networks where the number of NP links is
      controlled by the number of attached strands. The large length scale of the DNA
      links relative to the core NP size opens the possibility for the formation of
      interpenetrating networks that give rise to multiple thermodynamically distinct
      states. We find that the 3-functionalized NP have only a single phase transition
      between a dilute solution of NPs and an assembled network state. 4-Functionalized
      NP (with tetrahedral symmetry) exhibit four amorphous phases, or polyamorphism,
      each higher density phase consisting of an additional interpenetrating network.
      The two investigated geometries of 5-functionalized NP both exhibit two phase
      transitions and three amorphous phases. Like the 4-functionalized NP, the highest
      density phase consists of interpenetrating networks, demonstrating that regular
      symmetry is not a prerequisite for interpenetration to produce thermodynamically
      distinct phases. The width of the coexistence regions for all phase transitions
      increases with increasing functionality. Finally, for 6-functionalized NP with
      octahedral symmetry, the possibility of observing disordered phases with
      significantly bonded particles is preempted by the formation of ordered crystal
      phases. Interestingly, the extreme softness of the potential combined with the
      directional interaction allows for the formation of (at least) six distinct
      crystalline structures (i.e., polymorphism) consisting of up to six
      interpenetrating simple cubic lattices.

PMID- 19852478
TI  - Three-dimensional simulations of liquid bridges between two cylinders: forces,
      energies, and torques.
AB  - We present numerical simulations of three-dimensional liquid bridges between two
      identical smooth and chemically homogeneous cylinders held at a fixed distance
      and angle one with respect to the other. Despite the limited range of parameters
      studied, an analysis of resultant forces, energies, and torques reveals a rich
      level of detail. For large enough separations between the cylinders, the bridges
      appear symmetric and stable in shape and are found to yield a negligible torque
      on the cylinders. The force of adhesion is found to be positive in this case (the
      cylinders are attracted one to the other). A reduction in the distance between
      the cylinders reveals different behavior depending on the particular value of the
      set of parameters considered. For example, it appears that while relatively low
      contact angle systems favor attractive (positive) forces and stable symmetric
      bridges for small separation distances, larger contact angles lead to the
      coexistence of stable asymmetric and (apparently) unstable symmetric solutions,
      mostly (and respectively) associated with near-zero and negative (repulsive)
      forces of adhesion. In addition, while the larger values of contact angles
      studied here (90 degrees, 110 degrees) are associated with barely detectable
      torques, smaller values of contact angle are found to be associated with torques
      acting to rotate cylinders into a position where they are parallel one with
      respect to the other.

PMID- 19852479
TI  - Charge interaction between particle-laden fluid interfaces.
AB  - Experiments are described where two oil/water interfaces laden with charged
      particles move at close proximity relative to one another. The particles on one
      of the interfaces were observed to be attracted toward the point of closest
      approach, forming a denser particle monolayer, while the particles on the
      opposite interface were repelled away from this point, forming a particle
      depletion zone. Such particle attraction/repulsion was observed even if one of
      the interfaces was free of particles. This phenomenon can be explained by the
      electrostatic interaction between the two interfaces, which causes surface
      charges (charged particles and ions) to redistribute in order to satisfy surface
      electric equipotential at each interface. In a forced particle oscillation
      experiment, we demonstrated the control of charged particle positions on the
      interface by manipulating charge interaction between interfaces.

PMID- 19852480
TI  - Structural rearrangements and interaction within H(II) mesophase induced by
      cosolubilization of vitamin E and ascorbic acid.
AB  - We investigated the effect of ascorbic acid (AA) cosolubilized with vitamin E
      (VE) on reverse hexagonal (H(II)) mesophase. The H(II) phase comprises monoolein
      (GMO)/d-alpha-tocopherol (VE) in a ratio of 90/10 by weight and 12.5 wt % water.
      The macrostructural characteristics of this system were determined by polarized
      light microscopy and small-angle X-ray scattering measurements. We used
      differential scanning calorimetry and attenuated total reflectance Fourier
      transform infrared to characterize the microstructure, the vibration of the
      functional groups, and the location of the AA guest molecule. AA was incorporated
      to the system in two steps: 1-4 wt % AA and 5-6 wt % AA. We compared this system
      to one containing tricaprylin as the oil phase, as previously reported. These
      measurements revealed that AA is localized first in the water rich-core and in
      the interface, and acts as a chaotropic molecule that decreases the water melting
      point. When a larger quantity of AA (5-6 wt %) is added, the system is saturated,
      and the AA is located in the inner cylinder and manifested by more moderate
      distortion. The addition of AA also causes alteration in the behavior of the GMO
      hydrocarbon chains and makes them more flexible. Further addition of AA caused
      the GMO hydrocarbon chain to be more solvated by the VE hydrocarbon chain and
      enabled additional migration of VE; hence a decrease in the hydrophobic melting
      temperature occurred (similar to tricaprylin). Increasing the amount of AA
      weakened the bonding between the GMO and water and created new bonds between AA
      and GMO and AA with water.

PMID- 19852481
TI  - Behavior of asphaltene model compounds at w/o interfaces.
AB  - Asphaltenes, present in significant amounts in heavy crude oil, contains
      subfractions capable of stabilizing water-in-oil emulsions. Still, the
      composition of these subfractions is not known in detail, and the actual
      mechanism behind emulsion stability is dependent on perceived interfacial
      concentrations and compositions. This study aims at utilizing polyaromatic
      surfactants which contains an acidic moiety as model compounds for the surface
      active subfraction of asphaltenes. A modified pulse-field gradient (PFG) NMR
      method has been used to study droplet sizes and stability of emulsions prepared
      with asphaltene model compounds. The method has been compared to the standard
      microscopy droplet counting method. Arithmetic and volumetric mean droplet sizes
      as a function of surfactant concentration and water content clearly showed that
      the interfacial area was dependent on the available surfactant at the emulsion
      interface. Adsorption of the model compounds onto hydrophilic silica has been
      investigated by UV depletion, and minor differences in the chemical structure of
      the model compounds caused significant differences in the affinity toward this
      highly polar surface. The cross-sectional areas obtained have been compared to
      areas from the surface-to-volume ratio found by NMR and gave similar results for
      one of the two model compounds. The mean molecular area for this compound
      suggested a tilted geometry of the aromatic core with respect to the interface,
      which has also been proposed for real asphaltenic samples. The film behavior was
      further investigated using a liquid-liquid Langmuir trough supporting the ability
      to form stable interfacial films. This study supports that acidic, or strong
      hydrogen-bonding fractions, can promote stable water-in-oil emulsion. The use of
      model compounds opens up for studying emulsion behavior and demulsifier
      efficiency based on true interfacial concentrations rather than perceived
      interfaces.

PMID- 19852482
TI  - Shear-induced phase separation in polyelectrolyte/mixed micelle coacervates.
AB  - A quantitative study of the shear-induced phase separation of a
      polycation/anionic-nonionic micelle coacervate is presented. Simultaneous
      rheology and small-angle light scattering (SALS) measurements allow the
      elucidation of micrometer-scale phase separation under flow in three coacervate
      solutions. Below 18 degrees C, all three of the coacervate solutions are
      optically clear Newtonian fluids across the entire shear rate range investigated.
      Once a critical temperature range and/or shear rate is achieved, phase separation
      is observed in the small-angle light scattering images and the fluid exhibits
      shear thinning. Two definitive SALS patterns demonstrate the appearance of
      circular droplets at low shear rates near the critical temperature and
      ellipsoidal droplets at higher temperatures and shear rates. The shear-induced
      droplets range in size from approximately 1 to 4 mum. The ellipsoidal droplets
      have aspect ratios as high as 4. A conceptual picture in which shear flow extends
      the polyelectrolyte chains of the clear coacervate liquid phase is proposed. The
      extended chains create interpolyelectrolyte-micelle interactions and promote
      expulsion of small ions from the complex, resulting in the formation of
      micrometer-scale phase-separated droplets.

PMID- 19852483
TI  - Hybrid heterojunction and photoelectrochemistry solar cell based on silicon
      nanowires and double-walled carbon nanotubes.
AB  - A hybrid solar cell model composed of a heterojunction cell and a
      photoelectrochemical (PEC) cell has been proposed and characterized. In the
      hybrid cell, a thin film of double-walled carbon nanotubes forms a heterojunction
      with the silicon nanowire (SiNW) array and also functions as the transparent
      counter electrode of the PEC cell. The cell performance can be readily tuned by
      controlling the SiNW density. Under AM 1.5G illumination, a power conversion
      efficiency of 1.29%, higher than those reported for SiNW array-based PEC cells,
      has been obtained.

PMID- 19852484
TI  - MgF(3)(-) and alpha-galactose 1-phosphate in the active site of beta
      phosphoglucomutase form a transition state analogue of phosphoryl transfer.
AB  - (19)F-based NMR analysis and hydrogen/deuterium primary isotope shifts establish
      the formation of a highly populated solution-state trigonal bipyramidal complex
      involving beta-phosphoglucomutase (beta-PGM), alpha-galactose 1-phosphate
      (alphaGal1P), and trifluoromagnesate (MgF(3)(-)), PGM-MgF(3)-alphaGal1P, that is
      a transition state analogue for phosphoryl transfer. Full backbone resonance
      assignment of the protein shows that its structure is in the closed conformation
      required for catalytic activity and is closely related to the corresponding
      complex with glucose 6-phosphate, which we have recently identified using NMR
      analysis in solution and X-ray crystallography in the solid state. The previous
      identification of three structural waters in a PGM-alphaGal1P binary substrate
      complex had indicated that, in the presence of alphaGal1P, magnesium ions, and
      fluoride, beta-PGM should indeed form a PGM-MgF(3)-alphaGal1P-TSA complex
      whereas, in the solid-state, apparently it did not. This cast doubt on the
      validity of the interpretation of MgF(3)(-) complexes. The present work
      establishes that, in solution, the expectation that a PGM-MgF(3)-alphaGal1P-TSA
      complex should readily form is fulfilled. These results thus refute the final
      evidence used to claim that the trigonal bipyramidal species observed in some
      solid-state structures of complexes involving beta-PGM are pentaoxyphosphorane
      intermediates.

PMID- 19852485
TI  - Thermochromic absorption and photoluminescence in [Pt(ppy)(mu-Ph2pz)]2.
AB  - The temperature effects on the spectral properties and photophysics of a new d(8)
      d(8) dinuclear Pt(II) chromophore, [Pt(ppy)(mu-Ph(2)pz)](2) (ppy is 2
      phenylpyridine and Ph(2)pz is 3,5-diphenylpyrazolate), have been investigated.
      The thermochromic shifts are tentatively ascribed to intramolecular sigma
      interactions between the two pseudocofacial d(z(2)) orbitals. Substantial
      emission profile changes occur in the solid state, solution, and doped polymer
      films.

PMID- 19852486
TI  - Dip-pen nanolithography of electrical contacts to single-walled carbon nanotubes.
AB  - This paper discusses a method for the direct patterning of Au electrodes at
      nanoscale resolution using dip-pen nanolithography, with proof-of-concept
      demonstrated by creating single-walled carbon nanotube devices. This technique
      enables insight into three key concepts at the nanoscale: using dip-pen
      nanolithography as an alternative to electron-beam lithography for writing
      contacts to carbon nanotubes, understanding the integrity of contacts and devices
      patterned with this technique, and on a more fundamental level, providing a
      facile method to compare and understand electrical and Raman spectroscopy data
      from the same isolated carbon nanotube. Electrical contacts to individual and
      small bundle single-walled carbon nanotubes were masked by an alkylthiol that was
      deposited via dip-pen nanolithography on a thin film of Au evaporated onto spin
      cast, nonpercolating, and highly isolated single-walled carbon nanotubes. A wet
      Au etching step was used to form the individual devices. The electrical
      characteristics for three different single-walled carbon nanotube devices are
      reported: semimetallic, semiconducting, and metallic. Raman analysis on
      representative devices corroborates the results from AFM imaging and electrical
      testing. This work demonstrates a technique for making electrical contact to
      nanostructures of interest and provides a platform for directly corroborating
      electrical and optical measurements. The merits of using dip-pen nanolithography
      include flexible device configuration (such as varying the channel length and the
      number, size, and orientation of contacts), targeted patterning of individual
      devices with imaging and writing conducted in the same instrument under ambient
      conditions, and negligible damage to single-walled carbon nanotubes during the
      fabrication process.

PMID- 19852487
TI  - Molecular insights into the self-aggregation of aromatic molecules in the
      synthesis of nanoporous aluminophosphates: a multilevel approach.
AB  - Fluorescence spectroscopy and a range of computer simulation techniques are used
      to study the structure directing effect of benzylpyrrolidine (BP) and (S)-(-)-N
      benzylpyrrolidine-2-methanol (BPM) in the synthesis of nanoporous
      aluminophosphate frameworks with AFI (one-dimensional channels) and SAO (three
      dimensional interconnected channels) topologies. We study the supramolecular
      chemistry of BP and BPM molecules in aqueous solution and compare it with the
      aggregation state of the molecules found when they are inside the AlPO nanopores
      after crystallization. The aggregation of the molecules within the structures can
      be explained by a combination of thermodynamic and kinetic effects. The former
      are given by the stability of the molecular species interacting with the oxide
      networks relative to their stability in solution; the latter depend on the
      aggregation behavior of the molecules in the synthesis gels prior to
      crystallization. Whereas BPM only forms one type of aggregate in solution, which
      has the appropriate conformation to match the empty channels of the forming
      nanoporous frameworks, BP forms aggregates with different molecular orientations,
      of which only one matches the framework interstices. This different
      supramolecular chemistry, together with the higher interaction of BPM with the
      oxide networks, makes BPM a better structure directing agent (SDA); it is also
      responsible for the higher incorporation of BPM as dimers in the frameworks,
      especially in the AFI structure, observed experimentally. The concentration of
      the SDA molecules in the gels, and so the density per volume of the SDAs,
      determines the exclusion zone from which the pores and/or cavities of the
      framework will arise, and so the porous network of the formed material. A clear
      relationship between the SDA density in solution and in the framework is
      observed, thus enabling an eventual control of the material density by adjusting
      the SDA concentration in the gels. The topological instability intrinsic to these
      open framework structures is compensated by a high host-guest interaction energy;
      the SAO topology is further stabilized by doping with Zn. Our computational
      results account for and rationalize all the effects observed experimentally,
      providing a complete picture of the mode of structure direction of these aromatic
      molecules in the synthesis of nanoporous aluminophosphates.

PMID- 19852488
TI  - Scanning tunneling microscopy characterization of the electrical properties of
      wrinkles in exfoliated graphene monolayers.
AB  - We report on the scanning tunneling microscopy study of a new class of
      corrugations in exfoliated monolayer graphene sheets, that is, wrinkles
      approximately 10 nm in width and approximately 3 nm in height. We found such
      corrugations to be ubiquitous in graphene and have distinctly different
      properties when compared to other regions of graphene. In particular, a "three
      for-six" triangular pattern of atoms is exclusively and consistently observed on
      wrinkles, suggesting the local curvature of the wrinkle provides a sufficient
      perturbation to break the 6-fold symmetry of the graphene lattice. Through
      scanning tunneling spectroscopy, we further demonstrate that the wrinkles have
      lower electrical conductance and are characterized by the presence of midgap
      states, which is in agreement with recent theoretical predictions. The observed
      wrinkles are likely important for understanding the electrical properties of
      graphene.

PMID- 19852489
TI  - Structural and electronic properties of PTCDA thin films on epitaxial graphene.
AB  - In situ low-temperature scanning tunneling microscopy is used to study the growth
      of 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA) on epitaxial graphene
      (EG) on 6H-SiC(0001), as well as on HOPG for comparison. PTCDA adopts a layer-by
      layer growth mode, with its molecular plane lying flat on both surfaces. The
      PTCDA films grow continuously over the EG step edges, but not on HOPG. STS
      performed on single-layer PTCDA on monolayer EG shows a wide band gap larger than
      3.3 eV, consistent with pristine PTCDA films. Synchrotron-based high-resolution
      photoemission spectroscopy reveals weak charge transfer between PTCDA and EG.
      This suggests weak electronic coupling between PTCDA and the underlying EG layer.

PMID- 19852491
TI  - High-throughput discovery of Mycobacterium tuberculosis protein tyrosine
      phosphatase B (MptpB) inhibitors using click chemistry.
AB  - A approximately 3500-member library of bidentate inhibitors against protein
      tyrosine phosphatases (PTPs) was rapidly assembled using click chemistry.
      Subsequent high-throughput screening had led to the discovery of highly potent
      (K(i) as low as 150 nM) and selective MptpB inhibitors, some of which represent
      the most potent MptpB inhibitors developed to date.

PMID- 19852490
TI  - Organocatalytic enantioselective cascade Michael-Michael-Wittig reactions of
      phosphorus ylides: one-pot synthesis of the all-cis trisubstituted
      cyclohexenecarboxylates via the [1 + 2 + 3] annulation.
AB  - The stereoselective synthesis of all-cis 5-nitro-4,6-diphenylcyclohex-1
      enecarboxylic ester has been achieved by an organocatalytic asymmetric Michael
      Michael-Wittig cascade reaction of phosphorus ylides, nitroolefins, and
      alpha,beta-unsaturated aldehydes with excellent enantioselectivities (up to >99%
      ee).

PMID- 19852492
TI  - Asymmetrically 4,7-disubstituted benzothiadiazoles as efficient non-doped
      solution-processable green fluorescent emitters.
AB  - Asymmetrically 4,7-disubstituted benzothiadiazole derivatives involving a
      carbazolyl moiety at one end and a solubilizing dendron at the opposite end have
      been synthesized and characterized. A two-layer electroluminescent device based
      on one of these solution-processed molecular emitters revealed a maximal luminous
      efficiency of approximately 10.6 cd A(-1) and green light emission with CIE
      coordinates (0.34, 0.58).

PMID- 19852493
TI  - 6-O-Modified beta-cyclodextrin enabling inclusion complex formation in nonpolar
      media.
AB  - Heptakis(6-O-tert-butyldimethylsilyl)-beta-cyclodextrin (TBDMS-beta-CD)
      effectively forms inclusion complexes with chlorinated benzenes in nonpolar
      solvents such as benzene-d(6) and cyclohexane-d(12). The inclusion selectivity
      toward 1,2- and 1,3-dichlorobenzenes can be switched by changing the solvent from
      benzene-d(6) to cyclohexane-d(12). Moreover, 1,2,4-trichlorobenzene (90 ppm) is
      perfectly removed from insulating oil by using TBDMS-beta-CD as an adsorbent.

PMID- 19852494
TI  - Identification of codon-specific serine to asparagine mistranslation in
      recombinant monoclonal antibodies by high-resolution mass spectrometry.
AB  - Translation errors in protein biosynthesis may result in low level amino acid
      misincorporation and contribute to product heterogeneity of recombinant protein
      therapeutics. We report the use of peptide map analysis by reversed-phase high
      performance liquid chromatography and high-resolution mass spectrometry to detect
      and identify mistranslation events in recombinant monoclonal antibodies expressed
      in mammalian cell lines including Chinese hamster ovary (CHO) cells.
      Misincorporation of an asparagine residue at multiple serine positions was
      detected as earlier-eluting peptides with masses 27.01 Da higher than expected.
      The exact positions at which misincorporation occurred were identified by tandem
      mass spectrometry of the asparagine-containing variant peptides. The identified
      asparagine misincorporation sites correlated with the use of codon AGC but with
      none of the other five serine codons. The relative levels of misincorporation
      ranged from 0.01%-0.2% among multiple serine positions detected across three
      different antibodies by targeted analysis of expected and variant peptides. The
      low levels of misincorporation are consistent with published predictions for in
      vivo translation error rates. Our results demonstrate that state-of-the-art mass
      spectrometry with a combination of high sensitivity, accuracy, and dynamic range
      provides a new ability to discover and characterize low level protein variants
      that arise from mistranslation events.

PMID- 19852495
TI  - Density functional theory study of finite carbon chains.
AB  - The structural, electronic, and vibrational properties of the free finite carbon
      chains and those encapsulated inside carbon nanotubes (CNTs) are studied by
      density functional theory calculations. The end effect and chain symmetry are
      found to play key roles in deciding the structural characteristics of the free
      finite carbon chains based on the parity of the carbon numbers. Due to the
      potential interaction between the carbon chains and CNTs, the electrons of the
      chain-CNT systems will redistribute, and some charges may transfer to the inner
      carbon chains from CNTs. We suggest that the attractive potential of chain atoms
      inside CNTs could be the driving force for formation of the linear carbon inside
      CNTs. Unexpectedly, we find that inside CNTs the carbon chains with even-numbered
      carbons present almost constant bond length alternation, which is independent of
      the chain length. This trend of the even-numbered carbon chains in CNTs helps to
      explain the universal experimental observation that the Raman peaks from chains
      in CNTs are within 1820-1860 cm(-1).

PMID- 19852496
TI  - Degradation of carbon-supported Pt bimetallic nanoparticles by surface
      segregation.
AB  - Surface segregation of the non-noble component of a Pt bimetallic core-shell
      catalyst can occur even at room temperature under typical fuel cell cathode
      application conditions. While in an alkaline environment the nanoparticles remain
      stable, and the alteration in the surface composition can be tracked in situ; in
      an acidic electrolyte, any non-noble alloying material at the surface would
      immediately dissolve into the electrolyte. Therefore, such catalysts are expected
      to degrade steadily during operation in an acidic fuel cell until only Pt is
      left.

PMID- 19852497
TI  - A multistep continuous-flow system for rapid on-demand synthesis of receptor
      ligands.
AB  - A multistep continuous-flow system for synthesis of receptor ligands by assembly
      of three variable building blocks in a single unbroken flow is described. The
      sequence consists of three reactions and two scavenger steps, where a Cbz
      protected diamine is reacted with an isocyanate, deprotected, and reacted further
      with an alkylating agent.

PMID- 19852498
TI  - Dramatic red-shifted fluorescence of [2.2]paracyclophanes with peripheral
      substituents attached to the saturated bridges.
AB  - A bridge-substituted [2.2]paracyclophane obtained from the organic solid state
      exhibits a dramatic red shift in fluorescence relative to [2.2]paracyclophane. A
      further red shift occurs upon alkylation of the pyridylcyclobutyl bridges. Our
      results demonstrate that [2.2]cyclophanes substituted at the bridge, despite not
      being attached via the extended pi-system, are promising building blocks in the
      development of optical materials.

PMID- 19852499
TI  - Diversity synthesis of N-substituted 2-amino-1,6-naphthyridine derivatives under
      microwave irradiation.
AB  - A sequential three-component reaction of 3,5-diarylidenepiperidin-4-one,
      malononitrile, and amine (such as aromatic amine, cyclopropanamine, and NH(4)OAc)
      in acetic acid under microwave irradiation has been developed. In this one-pot
      reaction, a series of new N-substituted 2-amino-1,6-naphthyridine derivatives
      were synthesized with excellent yields. This method has the advantages of
      operational simplicity and increased safety for small-scale fast synthesis of N
      aryl 2-amino-1,6-naphthyridines for biomedical screening.

PMID- 19852500
TI  - Transparent metal nanowire thin films prepared in mesostructured templates.
AB  - The preparation of conductive and transparent gold/silver nanowire mesh films is
      reported. The nanowires formed after the reduction of the metal ions was
      triggered and a thin growth solution film was spread on a substrate. Metal
      reduction progressed within a template of a highly concentrated surfactant liquid
      crystalline mesostructure formed on the substrate during film drying to form
      ordered bundles of ultrathin nanowires. The films exhibited metallic conductivity
      over large areas, high transparency, and flexibility.

PMID- 19852501
TI  - Self-assembly of 1-D n-type nanostructures based on naphthalene diimide-appended
      dipeptides.
AB  - n-Type 1D nanostructures are formed from the beta-sheet assembly of dipeptides
      bearing a 1,4,5,8-naphthalenetetracarboxylic acid diimide (NDI) side chain into
      either helical nanofibers or twisted nanoribbons. Amyloid-like 1-D helical
      nanofibers and twisted nanoribbons assemble in an aqueous solution depending on
      the placement of the NDI group. beta-Sheet-type hydrogen bonding and pi-pi
      association play important roles in directing the assembly process. A delicate
      balance between electrostatic repulsion and hydrophobic interactions is critical
      for self-assembly. Fluorescence lifetime and anisotropy experiments indicate that
      the nature of the intermolecular organization and packing within the
      nanostructures critically impacts intermolecular energy migration pi-electron
      delocalization.

PMID- 19852503
TI  - Photochemical gluing of colloidal particles by a simple interparticle
      polymerization route.
AB  - We have developed a simple strategy to chemically cross-link polystyrene latex
      spheres by UV-light-induced polymerization after the particles, which themselves
      were internally cross-linked with divinylbenzene (DVB), have been carefully
      swollen in aqueous dispersion with a small amount of the monomer styrene. As a
      proof of concept, aggregates were preformed by salt-induced aggregation, and
      successful fixation of the aggregate structure was quantitatively confirmed by
      dynamic light scattering after the sample was diluted with distilled water and
      treated with ultrasound. Under this treatment, non-UV-irradiated aggregates
      dispersed and the single particle size was recovered. This concept was
      successfully applied also to commercial latex particles. For the future,
      arranging the colloids in a well-defined way by laser traps before photo-cross
      linking opens up a facile method to prepare microscopic devices.

PMID- 19852502
TI  - A convenient catalyst for aqueous and protein Suzuki-Miyaura cross-coupling.
AB  - A phosphine-free palladium catalyst for aqueous Suzuki-Miyaura cross-coupling is
      presented. The catalyst is active enough to mediate hindered, ortho-substituted
      biaryl couplings but mild enough for use on peptides and proteins. The Suzuki
      Miyaura couplings on protein substrates are the first to proceed in useful
      conversions. Notably, hydrophobic aryl and vinyl groups can be transferred to the
      protein surface without the aid of organic solvent since the aryl- and
      vinylboronic acids used in the coupling are water-soluble as borate salts. The
      convenience and activity of this catalyst prompts use in both general synthesis
      and bioconjugation.

PMID- 19852504
TI  - Multi-gram scale synthesis of FR180204.
AB  - A concise synthesis of the ERK inhibitor FR180204 has been developed. The
      synthesis consists of six operationally simple steps and can be utilized to make
      multi-gram quantities of FR180204.

PMID- 19852505
TI  - Orientational order of fluorinated mesogens containing the 1,3,2-dioxaborinane
      ring: a multidisciplinary approach.
AB  - Orientational order properties of two fluorinated liquid crystals containing the
      1,3,2-dioxaborinane ring have been investigated by means of optical, dielectric,
      and (13)C and (19)F NMR spectroscopies. The optical birefringence and dielectric
      anisotropy values determined in the mesomorphic phases were analyzed in terms of
      well-established theoretical models to obtain the order parameters relative to
      the principal axis of the polarizability tensor and molecular dipole moment,
      respectively. A large set of data, including (13)C and (19)F chemical shift
      anisotropies and (13)C-(19)F and (1)H-(19)F couplings relative to nuclei on the
      aromatic rings, was acquired in the NMR experiments and analyzed to determine
      local order parameters (principal order parameter and biaxiality) for different
      rigid fragments of the mesogen aromatic core using advanced DFT methods for the
      calculation of geometrical parameters and chemical shift tensors. A critical
      analysis of the dependence of the order parameters on the data set employed and
      on the theoretical assumptions and approximations has also been performed. The
      orientational order parameters obtained using the different techniques are
      compared and discussed in relation to the reference frame associated with the
      anisotropic properties monitored.

PMID- 19852506
TI  - Deducing 2D crystal structure at the liquid/solid interface with atomic
      resolution: a combined STM and SFG study.
AB  - Sum frequency generation vibrational spectroscopy (SFG) has been applied to study
      two-dimensional (2D) crystals formed by an isophthalic acid diester on the
      surface of highly oriented pyrolytic graphite, providing complementary
      measurements to scanning tunneling microscopy (STM) and computational modeling.
      SFG results indicate that both aromatic and C=O groups in the 2D crystal tilt
      from the surface. This study demonstrates that a combination of SFG and STM
      techniques can be used to gain a more complete picture of 2D crystal structure,
      and it is necessary to consider solvent-2D crystal interactions and dynamics in
      the computer models to achieve an accurate representation of interfacial
      structure.

PMID- 19852507
TI  - One-pot synthesis of symmetric and unsymmetric 1,1-bis-indolylmethanes via tandem
      iron-catalyzed C-H bond oxidation and C-O bond cleavage.
AB  - The reactions of indoles with ethers give a variety of symmetric and unsymmetric
      1,1-bis-indolylmethane derivatives via iron-catalyzed C-H bond oxidation and C-O
      bond cleavage.

PMID- 19852508
TI  - Laser control of vibrational transfer based on exceptional points.
AB  - The coalescence of two Floquet resonances with complex quasi-energies in the
      photodissociation of a molecule can be reached through an appropriate choice of
      laser parameters (wavelength and intensity). The corresponding point in the
      parameter plane is called exceptional. We show that a condition for two
      resonances to yield such a point is that they correspond, respectively, to a
      shape-like resonance and a Feshbach-like resonance. We examine how the resonances
      behave along a contour in the parameter plane, which goes around the exceptional
      point. The resonances exchange their labels. This amounts to a laser control of
      the vibrational transfer of the undissociated molecules from one field-free state
      to another.

PMID- 19852509
TI  - Rapid deposition of hydrophobic nanoparticle monolayers onto hydrophilic surfaces
      from liquid-liquid interfaces.
AB  - Dense, hydrophobic coatings comprising hydrophilic nanoparticles are deposited
      rapidly from water/toluene emulsions. The process of deposition is driven by a
      subtle interplay between interfacial phenomena, electrostatic interparticle
      repulsions, and hydrogen bonding between the NPs and the substrate(s). The
      packing fractions and the plasmonic properties of the coatings can be controlled
      by the pH of the aqueous phase. Once formed, the coatings can be further
      functionalized without a loss of mechanical integrity.

PMID- 19852510
TI  - Probing the aggregated state of 4-(9-anthryl)-N,N-dimethylaniline by UV-vis
      absorption and fluorescence spectroscopy, microscopy, and crystallography.
AB  - The aggregated state of the electron donor-acceptor molecule, 4-(9-anthryl)-N,N
      dimethylaniline, abbreviated here as ADMA, has been studied by electronic
      absorption and fluorescence spectroscopy, microscopy, and crystallography. Self
      assembled aggregates have been prepared by reprecipitation method under various
      conditions without using any stabilizing agent and characterized by different
      microscopic techniques. These studies reveal spherical and platelike morphologies
      and both amorphous and crystalline nature of the aggregates, whose sizes vary
      between 250 and 600 nm. The optical properties of these well-characterized
      aggregates have been studied and compared with those in molecular form.
      Intermolecular interaction in the aggregates induces remarkable change in the
      absorption and fluorescence properties of this dipolar system, and the formation
      of stable aggregates can be conveniently followed by monitoring the spectral
      response of the system as a function of time. Intramolecular charge transfer
      process, which dominates the photophysical behavior of this molecular system,
      could not be observed in the solid or aggregated state. The nature of the
      intermolecular interactions responsible for the formation and stabilization of
      the aggregates has been identified from the spectral and crystal structure data
      of the system. The results highlight the scope of broadening the spectral
      response of the present system by exploiting the advantageous optical properties
      of the aggregated state of the molecule.

PMID- 19852511
TI  - Targeted delivery of antisense oligodeoxynucleotide by transferrin conjugated pH
      sensitive lipopolyplex nanoparticles: a novel oligonucleotide-based therapeutic
      strategy in acute myeloid leukemia.
AB  - Therapeutic use of oligodeoxynucleotides (ODNs) that hybridize to and
      downregulate target mRNAs encoding proteins that contribute to malignant
      transformation has a sound rationale, but has had an overall limited clinical
      success in cancer due to insufficient intracellular delivery. Here we report a
      development of formulations capable of promoting targeted delivery and enhanced
      pharmacologic activity of ODNs in acute myeloid leukemia (AML) cell lines and
      patient primary cells. In this study, transferrin (Tf) conjugated pH-sensitive
      lipopolyplex nanoparticles (LPs) were prepared to deliver GTI-2040, an antisense
      ODN against the R2 subunit of ribonucleotide reductase that has been shown to
      contribute to chemoresistance in AML. LPs had an average particle size around 110
      nm and a moderately positive zeta potential at approximately 10 mV. The ODN
      encapsulation efficiency of LPs was >90%. These nanoparticles could release ODNs
      at acidic endosomal pH and facilitate the cytoplasmic delivery of ODNs after
      endocytosis. In addition, Tf-mediated targeted delivery of GTI-2040 was achieved.
      R2 downregulation at both mRNA and protein levels was improved by 8-fold in
      Kasumi-1 cells and 2- to 20-fold in AML patient primary cells treated with GTI
      2040-Tf-LPs, compared to free GTI-2040 treatment. Moreover, Tf-LPs were more
      effective than nontargeted LPs, with 10 to 100% improvement at various
      concentrations in Kasumi-1 cells and an average of 45% improvement at 3 microM
      concentration in AML patient primary cells. Treatment with 1 microM GTI-2040-Tf
      LPs sensitized AML cells to the chemotherapy agent cytarabine, by decreasing its
      IC(50) value from 47.69 nM to 9.05 nM. This study suggests that the combination
      of pH sensitive LP formulation and Tf mediated targeting is a promising strategy
      for antisense ODN delivery in leukemia therapy.

PMID- 19852513
TI  - Enterobactin synthetase-catalyzed formation of P(1),P(3)-diadenosine-5'
      tetraphosphate.
AB  - The EntE enzyme, involved in the synthesis of the iron siderophore enterobactin,
      catalyzes the adenylation of 2,3-dihydroxybenzoic acid, followed by its transfer
      to the phosphopantetheine arm of holo-EntB, an aryl carrier protein. In the
      absence of EntB, EntE catalyzes the formation of Ap(4)A, a molecule that is
      implicated in regulating cell division during oxidative stress. We propose that
      the expression of EntE during iron starvation produces Ap(4)A to slow growth
      until intracellular iron stores can be restored.

PMID- 19852514
TI  - Apoptotic, regenerative, and immune-related signaling in human islets from type 2
      diabetes individuals.
AB  - Islet dysfunction is a primary cause of developing type 2 diabetes mellitus
      (T2DM). Events leading to islet failure are still poorly defined due to the
      complexity of the disease and scarcity of human T2DM islets. The aim of the
      present study was to identify cellular mechanisms involved in the T2DM
      pathophysiology by protein profiling islets obtained from T2DM individuals and
      age- and weight-matched controls using liquid chromatography Fourier transform
      ion cyclotron resonance mass spectrometry and surface enhanced laser
      desorption/ionization time-of-flight mass spectrometry. In T2DM islets, multiple
      differentially expressed proteins correlated with insulin secretion. When these
      T2DM islet proteins were analyzed for differential pathway activation, three of
      the five most activated pathways were pathways of cell arrest and apoptosis (p53,
      caspase, stress-activated), one represented immune-response (Fas), and the most
      activated pathway was connected with proliferation and regeneration (E2F). Among
      the inactivated pathways, three out of five were pathways of proliferation and
      regeneration (insulin, PRL, PDGF). The present study is the first to report
      differential activation of specific pathways during T2DM islet deterioration. The
      information about alterations in pathway signaling patterns may open new ways to
      develop strategies aimed at restoring islet cell function and survival.

PMID- 19852512
TI  - Impact of hydrogel nanoparticle size and functionalization on in vivo behavior
      for lung imaging and therapeutics.
AB  - Polymer chemistry offers the possibility of synthesizing multifunctional
      nanoparticles which incorporate moieties that enhance diagnostic and therapeutic
      targeting of cargo delivery to the lung. However, since rules for predicting
      particle behavior following modification are not well-defined, it is essential
      that probes for tracking fate in vivo are also included. Accordingly, we designed
      polyacrylamide-based hydrogel particles of differing sizes, functionalized with a
      nona-arginine cell-penetrating peptide (Arg(9)), and labeled with imaging
      components to assess lung retention and cellular uptake after intratracheal
      administration. Radiolabeled microparticles (1-5 microm diameter) and
      nanoparticles (20-40 nm diameter) without and with Arg(9) showed diffuse airspace
      distribution by positron emission tomography imaging. Biodistribution studies
      revealed that particle clearance and extrapulmonary distribution was, in part,
      size dependent. Microparticles were rapidly cleared by mucociliary routes but,
      unexpectedly, also through the circulation. In contrast, nanoparticles had
      prolonged lung retention enhanced by Arg(9) and were significantly restricted to
      the lung. For all particle types, uptake was predominant in alveolar macrophages
      and, to a lesser extent, lung epithelial cells. In general, particles did not
      induce local inflammatory responses, with the exception of microparticles bearing
      Arg(9). Whereas microparticles may be advantageous for short-term applications,
      nanosized particles constitute an efficient high-retention and non-inflammatory
      vehicle for the delivery of diagnostic imaging agents and therapeutics to lung
      airspaces and alveolar macrophages that can be enhanced by Arg(9). Importantly,
      our results show that minor particle modifications may significantly impact in
      vivo behavior within the complex environments of the lung, underscoring the need
      for animal modeling.

PMID- 19852515
TI  - Do biologically relevant compounds have more chance to be drugs?
AB  - To prove the innate advantages of endogenous compounds/fragments for drug
      discovery and development, a novel index termed biological relevance (BR) is
      proposed. The results clearly indicate its ability to distinguish between
      synthetic chemicals, bioactive compounds, drug candidates, and launched drugs.
      Primarily, the average BR of the databases investigated decreases in the order
      DNP > CMC > ACD-3D > MDDR. Second, for compounds with the same bioactivity, drugs
      (CMC) possess higher average BR than their candidates (MDDR). These results
      suggest that compounds with higher BR have more chance to survive the drug
      development pipeline. Third, the above conclusion is supported by the fact that
      compounds in the later development phases possess higher BR than those in the
      earlier phases. Comparisons were made between BR and other indices, including
      toxicity, druglikeness, and natural productlikeness.

PMID- 19852516
TI  - jSimMacs for GROMACS: a Java application for advanced molecular dynamics
      simulations with remote access capability.
AB  - Molecular dynamics (MD) is a technique to simulate movements of molecular
      structures to understand their functional behavior. GROMACS is a software package
      primarily developed for biological MD and offers a huge amount of possible
      options and settings for tailoring the simulations. This makes it powerful but
      also complicated to handle. We introduce jSimMacs, a Java application for
      creating molecular dynamics projects in GROMACS. It simplifies the handling of
      files and options via an intuitive user interface. Users unexperienced in MD can
      work along prepared lines, while experts may enjoy a significant relief from the
      tedium of typing and scripting. Furthermore, jSimMacs supports 3D interactivity
      and the launch of remote projects on other computers accessible via networks.
      Thus, jSimMacs not only opens GROMACS to a broader public but also eases the
      burden of performing series of MD runs, as necessary in parameter studies.

PMID- 19852517
TI  - Structural and catalytic characterization of a heterovalent Mn(II)Mn(III) complex
      that mimics purple acid phosphatases.
AB  - The binuclear heterovalent manganese model complex [Mn(II)Mn(III)(L1)(OAc)(2)]
      ClO(4) x H(2)O (H(2)L1 = 2-(((3-((bis(pyridin-2-ylmethyl)amino)methyl)-2-hydroxy
      5-methylbenzyl)(pyridin-2-ylmethyl)amino)-methyl)phenol) has been prepared and
      studied structurally, spectroscopically, and computationally. The magnetic and
      electronic properties of the complex have been related to its structure. The
      complex is weakly antiferromagnetically coupled (J approximately -5 cm(-1), H = 
      2J S(1) x S(2)) and the electron paramagnetic resonance (EPR) and magnetic
      circular dichroism (MCD) spectra identify the Jahn-Teller distortion of the
      Mn(III) center as predominantly a tetragonal compression, with a significant
      rhombic component. Electronic structure calculations using density functional
      theory have confirmed the conclusions derived from the experimental
      investigations. In contrast to isostructural M(II)Fe(III) complexes (M = Fe, Mn,
      Zn, Ni), the Mn(II)Mn(III) system is bifunctional possessing both catalase and
      hydrolase activities, and only one catalytically relevant pK(a) (= 8.2) is
      detected. Mechanistic implications are discussed.

PMID- 19852518
TI  - Redox effects on the coordination geometry and heme conformation of bis(N
      methylimidazole) complexes of superstructured Fe-porphyrins. A spectroscopic
      study.
AB  - Electronic absorption, electron paramagnetic resonance (EPR), and Soret-excited
      resonance Raman (RR) spectra are reported for bis(N-alkylimidazole) complexes of
      various iron(III)-"basket-handle" (Fe(III)BHP(+)) and "picket-fence"
      (Fe(III)PFP(+)) porphyrins in methylene chloride. The Fe(III)BHP(+) derivatives
      consist of four cross-trans (CT) and two adjacent-cis (AC) -linked in which the
      composition and the length of the handles are variable (CT
      Fe(III)[(C(11)Im)(2)(+)], CT and AC Fe(III)[((C(4))(2)phi)(2)](+), CT
      Fe(III)[((C(3))(2)phi)(C(12))](+), CT and AC Fe(III)[((C(3))(2)phi)(2)](+)). The
      meso-alphaalpha betabeta and meso-alphabeta alphabeta atropisomers of Fe(III)
      tetrakis(o-pivalamidophenyl)-porphyrins represents the Fe(III)PFP(+) derivatives
      (Fe(III)alphaalpha betabeta-T(piv)PP(+) and Fe(III)alphabeta alphabeta
      T(piv)PP(+), respectively). The absorption and RR data obtained for these ferric
      compounds were compared to those previously published for the homologous ferrous
      complexes (Picaud, T., Le Moigne, C., Loock, B., Momenteau, M. and Desbois, A. J.
      Am. Chem. Soc. 2003, 125, 11616 and Le Moigne, C., Picaud, T., Boussac, A.,
      Loock, B., Momenteau, M. and Desbois, A. Inorg. Chem. 2003, 42, 6081). The Soret
      band position of the eight investigated ferric compounds is observed between 417
      and 424 nm, indicating that none of the complexes possesses a planar heme. The
      EPR spectra show that most of the Fe(III)BHP(+) complexes and all the
      Fe(III)PFP(+) complexes are rhombic B-type hemichromes (g(max) = 2.86-2.96).
      Notable exceptions concern the bis(N-methylimidazole) complexes of two CT
      Fe(III)BHP(+). The Fe(III)BHP(+) with the shortest handles
      (Fe(III)[((C(3))(2)phi)(2)](+)) exhibits a g value at 2.80. When the handles are
      lengthened by two methylene units (Fe(III)[((C(3))(2)phi)(2)](+)), the EPR
      spectrum corresponds to a mixture of two "highly anisotropic low-spin " or "large
      g(max)" type I EPR signals, a major species at g = 3.17 and a minor species at g
      = 3.77. All these EPR data were converted in terms of dihedral angle formed by
      the rings of the axial ligands. The RR spectra of the Fe(III)BHP(+) and
      Fe(III)PFP(+) complexes exhibited variable frequencies for the structure
      sensitive nu(2) and nu(8) lines (1558-1563 cm(-1) and 386-401 cm(-1),
      respectively). In considering the ability of the different superstructures to
      stabilize particular out-of-plane distortions, this vibrational information was
      analyzed in terms of heme structure through changes in core size and Fe
      N(pyrrole) bond length, in relation to changes in coordination geometry. The
      bis(N-methylimidazole) complex of Fe(III)[((C(3))(2)phi)(2)](+) was found to be
      the most distorted with a strongly ruffled tetrapyrrole. Because of a handle
      asymmetry, the heme conformation of the bis(N-methylimidazole) complex of
      Fe(III)[((C(3))(2)phi)(C(12))](+) was deduced to be a composition of ruffled and
      domed structures. The heme structure of the other complexes is a mixture of
      ruffled and saddled or ruffled and waved conformations. Taking into account our
      previous data on the ferrous series, this investigation provides information
      about the reorganization of the heme structure upon iron oxidation. The general
      trend is a decrease of either the core-size, or the Fe-N(pyrrole) bond length, or
      both. However, we demonstrated that the heme superstructures precisely control
      the nature and the extent of the tetrapyrrole reshaping. These results point out
      similar possible effect in the heme proteins, considering both an analogy between
      porphyrin superstructures and amino acids forming the heme sites and the
      diversity of the heme environments in the proteins.

PMID- 19852519
TI  - One-pot, template syntheses of a new class of metallomacrocycles with a
      tetraoxime cyclic skeleton.
AB  - Most common macrocycles such as crown ethers, porphyrins, and macrocyclic
      polyamines show versatile, excellent functions in a variety of research fields
      such as coordination chemistry, supramolecular chemistry, analytical chemistry,
      and material sciences. Thus, the rational design of a new class of readily
      synthesized macrocyclic metal ligands is a key to the development of a new
      category of functionalized macrocyclic metal complexes. Herein, we report one
      pot, template syntheses of a new class of metallomacrocycles with a 16-membered
      tetraoxime cyclic skeleton from a dioxime in the presence of a template
      transition-metal ion such as Fe(2+), Ni(2+), Cu(2+), Co(2+), or Ag(+). These
      metal ions can be easily removed from the mononuclear metallomacrocycles, and,
      for example, the metal-free tetraoxime ligand was obtained in 90% yield when
      Fe(2+) was used as the template. It would appear that this one-pot, metal
      template cyclization efficiently proceeds through continual metal-mediated oxime
      exchange reactions. Interestingly, Pd(2+), which does not afford any cyclized
      products, formed a 1:1 complex with the macrocyclic ligand. The molecular
      structures of the metal-free ligand, its 1:1 metal complexes with Fe(2+), Ni(2+),
      Cu(2+), Pd(2+), and Ag(+), and a dinuclear complex with Ag(+) were fully
      determined by single-crystal X-ray analyses. UV-visible absorption spectra and
      cyclic voltammetry measurements of these complexes are also reported.

PMID- 19852520
TI  - Morphology-controlled synthesis of inorganic nanocrystals via surface
      reconstruction of nuclei.
AB  - The growth mechanism of shape-selected synthesis of nanocrystals in all systems
      can be attributed to an oriented surface assembly process of growth units, in the
      present of additives or not. In this article, we present an example displaying
      the influence of the surface reconstruction process of nuclei on the shape
      selected growth behaviors of inorganic nanocrystals. The basic principle lies in
      the sufficient diffusion of growth units on crystal surfaces according to
      Kossel's growth model. Shape-controlled octahedral and truncated octahedral
      crystals of zinc tin oxide (ZTO) were successfully synthesized by pretreating
      precursors at room temperature without any surfactants. And, the method can be
      applied to CaSn(OH)(6), SrSn(OH)(6), and ZnO. We also found out that there is a
      linear correlativity between the truncated degrees and the amount of NaOH when
      studying morphological evolution behavior from an octahedron to a cube of ZTO.

PMID- 19852521
TI  - Mercury(II) recognition and fluorescence imaging in vitro through a 3D
      complexation structure.
AB  - 8,8'-(1,4,10,13-Tetrathia-7,16-diazacyclooctadecane-7,16-diyl)
      bis(methylene)diquinolin-7-ol (TTBQ) was synthesized and proved to selectively
      recognize Hg(2+), forming a Hg(2+)/TTBQ complex with an association constant
      (K(a)) as large as approximately 1.3 x 10(4) +/- 520 M(-1) in aqueous solution.
      Single crystals of TTBQ and a TTBQ-Hg(2+) complex have also been successfully
      grown, in which the latter unambiguously revealed a cagelike configuration
      consisting of thiol-crown and dual 7-hydroxyquinoline moieties to firmly trap
      Hg(2+). This 3D-complexation structure accounts for approximately 25-fold
      luminescence enhancement and a detection limit of sub-microM in water for sensing
      Hg(2+). Great selectivity toward Hg(2+) has been exhibited over alkali- and
      alkaline-earth metal ions, first-row transition-metal ions, and other cations
      studied. This chemosensor is particularly suited for the detection of Hg(2+) in a
      pH range of 5.5 to 7.5. This, in combination with its fine biocompatibility,
      leads to the success toward in vitro mercury recognition based on fluorescence
      imaging.

PMID- 19852522
TI  - Composition and structure of polynuclear chromium(III) hydroxo complexes.
AB  - The structures of the polynuclear hydrolysis complexes of chromium(III) formed in
      acidic and alkaline aqueous solution have been determined by means of extended X
      ray absorption fine structure and large angle X-ray scattering. Chromium(III) is
      present as mononuclear hydrated ions below pH 3-4, with the upper limit depending
      on concentration, ionic strength, and temperature. Chromium(III) hydrolyzes in
      aqueous solution above this pH in concentrated aged solutions to mainly cationic
      tetrameric complexes containing both single and double hydroxo bridges between
      the chromium(III) ions. Above pH 5, the solubility of chromium(III) decreases
      sharply to form solid hydrated chromium(III) hydroxide. The solubility of
      chromium(III) increases sharply at elevated pH, and fairly concentrated solutions
      can be prepared in concentrated aqueous solutions of sodium hydroxide. According
      to the literature, mononuclear tetrahydroxochromate(III) complexes, Cr(OH)(4)(-),
      are formed in alkaline aqueous solution. However, this study shows polymeric
      chains of six-coordinated chromium(III) ions connected through double hydroxo
      bridges and with two terminal hydroxo groups giving an overall composition of
      (Cr(OH)(4))(n)(n-). This polymer is stable for a long time in solution at pH =
      15. However, at pH < 15, this polymer precipitates slowly with time, over months,
      to an amorphous phase with a structure around chromium similar to that in alpha
      chromium(III) oxide hydroxide.

PMID- 19852523
TI  - Predictors of treatment response in chronic hepatitis B.
AB  - The ultimate goal of treatment for chronic hepatitis B is to reduce liver-related
      complications and mortality. Sustained hepatitis B e antigen (HBeAg)
      seroconversion and hepatitis B surface antigen (HBsAg) clearance 6-12 months
      after stopping treatment are the short-term surrogate outcomes for interferon or
      peginterferon therapy. As most patients require long-term nucleos(t)ide analogue
      treatment, which also has the risk of drug resistance in the case of incomplete
      viral suppression, maintained hepatitis B virus (HBV) DNA suppression to an
      undetectable level is the appropriate surrogate outcome. Because no antiviral
      treatment is perfect, it is desirable for treatment response to be predicted and
      the treatment regimen modified accordingly. At baseline, high ALT and low HBV DNA
      levels can predict response to both (peg)interferon and nucleos(t)ide analogues.
      Genotype A HBV responds best to peginterferon but HBV genotype has no predictive
      value for nucleos(t)ide analogue treatment. HBV DNA is a good on-treatment
      predictor of response for nucleos(t)ide analogues but not for (peg)interferon.
      The data supporting the use of quantitative HBsAg and HBeAg to predict response
      to peginterferon is stronger than that for nucleos(t)ide analogues. In
      conclusion, predictors of response are useful to provide the most appropriate
      antiviral therapy to the most suitable patients, in order to achieve the best
      response and improve the clinical outcome of chronic hepatitis B patients.

PMID- 19852524
TI  - Enzyme replacement therapy for Fabry disease: a systematic review of available
      evidence.
AB  - Fabry disease is a progressive and life-threatening glycolipid storage disorder
      affecting both males and females. The primary driver of the disease is the
      accumulation of glycolipids (globotriaosylceramide [GL-3]) in a variety of cell
      types, including vascular endothelial cells, a range of renal cell types,
      cardiomyocytes and neurons, which is caused by deficient activity of the
      lysosomal enzyme, alpha-galactosidase. The disease typically presents during
      childhood or adolescence. First manifestations reflect involvement of small nerve
      fibres of the peripheral and autonomic nervous systems. With age, severe
      complications involving the kidneys, heart and brain cause considerable morbidity
      and premature death. Outside the US, enzyme replacement therapy (ERT) with
      agalsidase alfa 0.2 mg/kg every other week (EOW) and agalsidase beta 1.0 mg/kg
      EOW is available for the treatment of patients with Fabry disease, while
      agalsidase beta 1.0 mg/kg EOW is the only approved drug in the US. To analyse the
      evidence for ERT, a systematic review of the literature was performed to identify
      prospectively designed randomized, controlled trials (RCTs) and open-label
      studies on the efficacy of agalsidase alfa and agalsidase beta. MEDLINE and
      EMBASE databases were searched; inclusion criteria for the systematic review were
      prospectively designed clinical studies evaluating ERT with quantifiable
      endpoints: double-blind and open-label studies were eligible. Exclusion criteria
      were review articles, case reports, case studies, letters to the editor and
      articles based on registry data (Fabry Outcome Survey or Fabry Registry). In
      addition, any studies with a retrospective design or data based on post hoc
      analyses were excluded. The evidence was reviewed with respect to the clinical
      benefits of ERT at the level of the end organ. A total of 9 RCTs and 23 open
      label studies were identified for inclusion. The efficacy of ERT in Fabry disease
      has been measured against a variety of endpoints, the majority of which were
      subclinical parameters rather than clinical outcomes. Plasma levels of GL-3
      together with accumulation in the kidney, heart and skin were the most commonly
      studied endpoints, followed by renal endpoints of proteinuria and glomerular
      filtration rate, whereas cardiac and neurological endpoints were not commonly
      studied. To date, only one RCT with ERT defined hard clinical outcomes in the
      form of cardiac, renal or cerebrovascular events, or death as its primary
      endpoint. The currently available data from prospective RCTs and open-label
      studies in patients with Fabry disease are more robust for ERT at a dose of 1
      mg/kg EOW than a dose of 0.2 mg/kg EOW, although the beneficial effects of ERT
      with either dose or preparation are variable.

PMID- 19852525
TI  - Medical therapy of acromegaly: efficacy and safety of somatostatin analogues.
AB  - Acromegaly is a chronic disease with signs and symptoms due to growth hormone
      (GH) excess. The most frequent cause of acromegaly is a GH-producing pituitary
      adenoma. Chronic GH excess is accompanied by long-term complications of the
      locomotor (arthrosis) and cardiovascular (atherosclerosis, cardiomyopathy)
      systems and is, when untreated, associated with an increased mortality. The aim
      of treatment of acromegaly is to improve symptoms, to achieve local tumour mass
      control, and to decrease morbidity and mortality. Treatment options include
      surgery, medical therapy and radiotherapy. Transsphenoidal surgery is the first
      choice of treatment when a definitive cure can be achieved, particularly in the
      case of microadenomas and when decompression of surrounding structures (optic
      chiasm, ophthalmic motor nerves) is indicated. Primary medical therapy has been
      increasingly applied in recent years, especially when a priori chances of
      surgical cure are low (because of adenoma size and localization) and in patients
      with advanced age and/or serious co-morbidity. In addition, preoperative primary
      medical therapy may result in tumour shrinkage, facilitating tumour resection,
      and may reduce perioperative complications due to GH excess. Within the spectrum
      of medical therapy, long-acting somatostatin analogues (somatostatins) are
      considered as first-line treatment. Treatment with somatostatin analogues results
      in GH control in approximately 60% of patients. In addition, somatostatin
      analogues induce tumour shrinkage in 30-50% of patients, particularly when
      applied as primary therapy. Prolonged treatment with somatostatin analogues
      appears to be safe and is usually well tolerated. The currently available
      somatostatin analogues, octreotide and lanreotide, seem to be equally effective;
      however, this should still be evaluated in prospective, randomized trials
      evaluating efficacy with respect to GH control and tumour shrinkage. In patients
      with an insufficient clinical and biochemical response to somatostatin analogues,
      combination therapy with dopamine receptor agonists or the GH receptor antagonist
      pegvisomant usually leads to disease control. New developments in the medical
      therapy of acromegaly include the universal somatostatin receptor agonist
      pasireotide, which has a broader affinity for all somatostatin receptor (sst)
      subtypes compared with the currently available somatostatin analogues with
      preferential affinity for the sst2 receptor, and chimeric compounds that interact
      with both somatostatin and dopamine receptors with synergizing effects on GH
      secretion.

PMID- 19852527
TI  - Tenofovir disoproxil fumarate: in chronic hepatitis B.
AB  - Tenofovir disoproxil fumarate (tenofovir DF) is an orally administered ester
      prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor that shows
      potent in vitro activity against both hepatitis B virus (HBV) and HIV-1. As a
      component of antiretroviral combination therapy regimens, tenofovir DF is well
      established in the treatment of adults with HIV-1 infection. Tenofovir DF,
      administered once daily, is also used in the treatment of adults with chronic
      hepatitis B (CHB) [the main focus of this profile]. In CHB, the efficacy of
      tenofovir DF against HBV has been evaluated in two large randomized, phase III
      clinical studies in hepatitis B e antigen (HBeAg)-negative or HBeAg-positive
      adults, with compensated liver function. The trials (planned duration 8 years)
      were double-blind for the first 48 weeks; thereafter, patients received open
      label tenofovir DF. Results at 48 and 96 weeks are available. In these studies,
      at week 48, a significantly greater proportion of recipients of tenofovir DF 300
      mg once daily than oral adefovir dipivoxil 10 mg once daily achieved a complete
      response (primary endpoint). A complete response was defined as a reduction from
      baseline in plasma HBV DNA level to <400 copies/mL and histological improvement
      (reduction of 2 or more points in Knodell necroinflammatory score without
      worsening of fibrosis). The efficacy of tenofovir DF in the treatment of CHB was
      also demonstrated over a 96-week treatment period in both studies. Tenofovir DF
      was generally well tolerated by adults with CHB in the two phase III trials.

PMID- 19852526
TI  - Immunosuppressive drugs in kidney transplantation: impact on patient survival,
      and incidence of cardiovascular disease, malignancy and infection.
AB  - Renal transplant recipients have increased mortality rates when compared with the
      general population. The new immunosuppressive drugs have improved short-term
      patient survival up to 95% at 1-2 years, but these data have to be confirmed in
      long-term follow-up. Furthermore, no particular regimen has proved to be superior
      over others with regard to patient survival. Cardiovascular diseases are the most
      common cause of mortality in renal transplant recipients and while no
      immunosuppressive drug has been directly associated with cardiovascular events,
      immunosuppressive drugs have different impacts on traditional risk factors.
      Corticosteroids and ciclosporin are the agents with the most negative impact on
      weight gain, blood pressure and lipids. Tacrolimus increases the risk of new
      onset diabetes mellitus. Sirolimus and everolimus have the most impact on risk
      factors for post-transplant hyperlipidaemia. Modifications in immunosuppression
      could improve the cardiovascular profile but there is little evidence regarding
      the beneficial effects of these changes on patient outcomes. Malignancies are
      also an increasing cause of mortality, overtaking cardiovascular disease in some
      series. Induction therapy, azathioprine and calcineurin inhibitors (CNIs) are
      probably the immunosuppressive agents most linked with post-transplant
      malignancies. Mycophenolate mofetil (MMF) has no negative impact on the incidence
      of malignancies. Target of rapamycin (mTOR) inhibitors have antioncogenic
      properties and they are associated with a lower incidence of malignancies. In
      addition, these agents have been recommended for use to decrease the dose or
      withdrawal of CNIs in patients with malignancies. Infections are still an
      important cause of morbidity and mortality in renal transplant recipients. Some
      immunosuppressive agents such as MMF increase the incidence of cytomegalovirus
      infection and the need for prophylactic measures in risk recipients. The use of
      potent immunosuppressive therapy has resulted in the appearance of BK virus
      nephropathy, which progresses to graft failure in a high percentage of patients.
      Although first associated with tacrolimus and MMF immunosuppression, recent data
      suggest that BK nephropathy appears with any kind of triple therapy. In
      conclusion, reducing risk factors for patient death should be a major target to
      improve outcomes after renal transplantation. Effort should be made to control
      cardiovascular diseases, malignancies and infections with improved use of
      immunosuppressive drugs. Preliminary results with belatacept suggest its safety
      and efficacy, and open new perspectives in the immunosuppression of de novo renal
      transplant recipients.

PMID- 19852528
TI  - Palonosetron: in the prevention of nausea and vomiting.
AB  - Palonosetron is a second-generation serotonin 5-HT3 receptor antagonist, with a
      distinct pharmacological profile that differs from first-generation 5-HT3
      receptor antagonists. Intravenous palonosetron is widely indicated for the
      prevention of chemotherapy-induced nausea and vomiting (CINV) in the acute and
      delayed phases following moderately emetogenic chemotherapy (MEC) and the
      prevention of CINV in the acute phase following highly emetogenic chemotherapy
      (HEC). In the US, oral palonosetron is approved for the prevention of CINV in the
      acute phase following MEC (although this formulation is not currently available),
      and intravenous palonosetron is indicated for the prevention of postoperative
      nausea and vomiting (PONV) in the first 24 hours following surgery. All
      indications are currently limited to adult patients. Intravenous palonosetron was
      noninferior to intravenous ondansetron (with statistically greater efficacy than
      ondansetron) or dolasetron in preventing CINV following MEC, or to intravenous
      ondansetron or granisetron in preventing CINV following HEC, in the acute phase.
      Statistically greater efficacy was seen with intravenous palonosetron than
      ondansetron or dolasetron in preventing CINV following MEC in the delayed phase.
      Oral palonosetron was noninferior to intravenous palonosetron in preventing CINV
      in the acute phase in patients receiving MEC. Intravenous palonosetron was
      superior to placebo in preventing PONV in the first 24 hours following surgery.
      Palonosetron was generally well tolerated in clinical trials. Intravenous
      palonosetron is a valuable option in the prevention of acute- and delayed-phase
      CINV in adult patients receiving MEC, and of acute-phase CINV in patients
      receiving HEC. Oral palonosetron is likely to be a useful addition to oral
      formulations of other 5-HT3 receptor antagonists in preventing CINV in patients
      receiving MEC. Intravenous palonosetron is a useful alternative to currently
      recommended agents in PONV prevention.

PMID- 19852529
TI  - Pemetrexed: a review of its use in the management of advanced non-squamous non
      small cell lung cancer.
AB  - Pemetrexed (Alimta) is a multi-targeted antifolate cytotoxic agent available for
      use in the treatment of adults with advanced non-squamous non-small cell lung
      cancer (NSCLC). It is indicated as initial therapy in combination with cisplatin,
      as monotherapy after prior chemotherapy, and as maintenance monotherapy in
      patients with locally advanced or metastatic non-squamous NSCLC. Pemetrexed has
      demonstrated efficacy and is generally well tolerated as a first-line therapy (in
      combination with cisplatin) and as second-line or maintenance monotherapy in
      advanced non-squamous NSCLC. While the survival benefits of comparator
      chemotherapies are retained with pemetrexed, pemetrexed has tolerability
      advantages that may also translate to pharmacoeconomic benefits, although this
      has yet to be shown in robust pharmacoeconomic analyses. Pemetrexed is an
      important option for the management of NSCLC, in particular as targeted therapy
      in patients with non-squamous histology.

PMID- 19852530
TI  - Gefitinib: a review of its use in the treatment of locally advanced/metastatic
      non-small cell lung cancer.
AB  - Gefitinib (Iressa) is an epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor that offers treatment for patients with locally advanced or metastatic
      non-small cell lung cancer (NSCLC), in particular in those who are harbouring
      EGFR mutations. In a large phase III trial (IPASS) in chemotherapy-naive Asian
      patients with adenocarcinoma who were never smokers or former light smokers, oral
      gefitinib was more effective than carboplatin plus paclitaxel in prolonging
      progression-free survival (PFS). In a prespecified subgroup analysis, EGFR
      mutation-positive status was associated with a positive response to gefitinib
      treatment. Furthermore, a trial in chemotherapy-naive patients with NSCLC that
      was restricted to those with EGFR mutations found that gefitinib recipients had
      significantly longer PFS than carboplatin plus paclitaxel recipients. In large
      phase III trials (INTEREST, V-15-32) in unselected, previously treated patients,
      the overall survival (OS) in gefitinib recipients was noninferior to, or not
      significantly different from, that of docetaxel recipients. In a placebo
      controlled trial in previously treated patients (ISEL), pre-planned subgroup
      analyses in Asian patients and non-smokers showed that in these subgroups
      gefitinib prolonged OS, and that EGFR biomarkers predicted a positive response to
      gefitinib. Gefitinib was also associated with greater improvements in quality of
      life (QOL) in both chemotherapy-naive and previously treated patients. A head-to
      head trial of gefitinib versus erlotinib in EGFR-mutation-positive patients would
      help position gefitinib relative to erlotinib in this population. Further
      research is also required to identify factors associated with non-response to
      EGFR-tyrosine-kinase inhibitors in EGFR-mutation-positive patients. Gefitinib was
      a generally well tolerated treatment, with rash and diarrhoea being the most
      common treatment-emergent adverse events. Interstitial lung disease (ILD) is a
      serious co-morbidity of NSCLC associated with gefitinib and other cancer
      treatments; ILD-type events occurred with an overall incidence of approximately
      1% in gefitinib recipients participating in clinical trials, and were more common
      in Asian patients. Notably, gefitinib was associated with significantly fewer
      haematological and neurological adverse effects than comparator chemotherapy
      regimens. Gefitinib as monotherapy is an effective treatment for patients with
      locally advanced or metastatic NSCLC with EGFR mutations.

PMID- 19852531
TI  - Lanthanum carbonate: a review of its use in lowering serum phosphate in patients
      with end-stage renal disease.
AB  - Orally administered lanthanum carbonate (Fosrenol) dissociates in the acid
      environment of the upper gastrointestinal tract to release the cation lanthanum,
      which then binds dietary phosphate. Lanthanum carbonate was effective in reducing
      levels of serum phosphate and serum calcium x phosphate product and then
      maintaining these levels within target ranges for up to 6 years in adult patients
      with end-stage renal disease (ESRD) on haemodialysis or peritoneal dialysis. The
      reduction in serum phosphate levels with lanthanum carbonate was generally
      similar to that with calcium carbonate or sevelamer hydrochloride. This agent was
      generally well tolerated, with the most frequently reported adverse events being
      gastrointestinal in nature and occurring at a similar rate to that with calcium
      carbonate. However, lanthanum carbonate was associated with fewer episodes of
      hypercalcaemia than calcium carbonate. Overall, lanthanum carbonate is a valuable
      option for the reduction of serum phosphate levels in patients with ESRD on
      haemodialysis or peritoneal dialysis.

PMID- 19852532
TI  - Erratum: "Viscoelastic properties of crystals" [J. Chem. Phys. 131, 024115
      (2009)].

PMID- 19852534
TI  - Retraction: "The zero kinetic energy photoelectron spectra of the propargyl
      radical, C3H3" [J. Chem. Phys. 112, 2575 (2000)].

PMID- 19852533
TI  - Erratum: "Phase diagram of Hertzian spheres" [J. Chem. Phys. 131, 044514 (2009)].

PMID- 19852536
TI  - Endovascular coil occlusion of 152 middle cerebral artery aneurysms: initial and
      midterm angiographic and clinical results.
AB  - OBJECT: The object of this study was to evaluate the initial and mid-term
      angiographic and clinical results after endovascular coil occlusion of middle
      cerebral artery (MCA) aneurysms at the authors' institution. METHODS: The authors
      conducted a retrospective analysis of a consecutive series of 152 MCA aneurysms
      (73 ruptured) treated by endovascular coiling in 140 patients. Angiographic and
      clinical data at initial and midterm follow-up as well as procedure-related
      complications were prospectively registered. RESULTS: At discharge, favorable
      clinical outcomes (Glasgow Outcome Scale score of 1 or 2) were obtained in 89.3%
      of patients (125/140). Seven patients (5%) were in a vegetative state or had
      died. Complications were encountered in association with 11.8% of the procedures
      (18/152), and most (13/18) involved thromboembolic events (which led to permanent
      ischemia in 4 cases and death in 1). The overall procedure-related mortality rate
      was 0.7%, and the rates of permanent and transient morbidity were 2.6 and 2%,
      respectively. At a mean follow-up duration of 4.3 years there had been 4 cases of
      rebleeding: early rebleeding occurred during the initial postoperative period in
      3 cases and later in 1. Total or subtotal occlusion was obtained in 84.2% of
      aneurysms (128/152). At follow-up, this satisfactory occlusion persisted in 83.3%
      of aneurysms (110/132) at 1 year posttreatment, 79.5% (89/112) at 3 years, and
      80.2% (73/91) at 5 years. CONCLUSIONS: Risks and initial and midterm angiographic
      and clinical results after endovascular treatment of MCA aneurysms are nearly
      identical to other locations. Endovascular treatment may thus be proposed as an
      alternative to surgical clipping at this location. Nevertheless, a longer follow
      up period is necessary to determine its efficacy, particularly in cases of
      unruptured aneurysms.

PMID- 19852537
TI  - The impact of therapeutic modality on outcomes following repair of ruptured
      intracranial aneurysms: an administrative data analysis. Clinical article.
AB  - OBJECT: Enrolling a selected sample of ruptured intracranial aneurysms, the
      International Subarachnoid Aneurysm Trial (ISAT) found endovascular coiling to be
      superior to microsurgical clipping. The performance of coiling in a more general
      population of ruptured aneurysms has not been adequately studied. METHODS: Using
      provincial administrative data from Ontario, the authors conducted a
      retrospective cohort study of adult patients with subarachnoid hemorrhage (SAH)
      who underwent aneurysm repair. The exposure was defined as endovascular versus
      surgical aneurysm repair. The prespecified primary outcome was time to death or
      readmission for SAH. Data from the entire cohort were analyzed using a
      multivariable adjusted Cox proportional hazards model. Propensity scores were
      used to compare a matched subgroup of patients with aneurysms who had similar
      baseline characteristics. The potential impact of unmeasured confounding was
      assessed using sensitivity analysis. RESULTS: Between 1995 and 2004, 2342
      aneurysms were clipped and 778 were coiled in Ontario. The proportion of
      aneurysms treated by coiling increased steadily over time. In the adjusted
      analysis of the entire cohort, endovascular coiling was associated with a
      significantly increased hazard of death or SAH readmission (hazard ratio 1.25
      [95% CI 1.00-1.55], p = 0.04). Similar results were obtained from the propensity
      score matched analysis (hazard ratio 1.25 [95% CI 1.04-1.50], p = 0.02). Measures
      of procedural morbidity and mortality were not significantly different between
      groups. CONCLUSIONS: The results of the current analysis call into question the
      generalizability of the ISAT to all ruptured aneurysms. Given the limitations
      inherent in this form of analysis, further clinical studies-rigorously assessing
      the performance of endovascular therapy in patients with non-ISAT-like aneurysms
      are indicated.

PMID- 19852538
TI  - Microvascular decompression of the optic chiasm. Case report.
AB  - Elongation of the anterior cerebral artery (ACA) and subsequent compression of
      the chiasm rarely have been reported as causes of a visual field deficit. Neither
      has microvascular decompression of the chiasm been described in this
      circumstance. The authors report on a case of progressive visual deficits caused
      by compression of the optic apparatus by a right elongated ACA as documented on
      MR imaging. Microvascular decompression was proposed as treatment. The right A(1)
      segment was larger than usual and tortuous, transmitting its pulsations into the
      chiasm. A piece of Teflon was inserted between the A(1) segment and the chiasm.
      Following surgery, the visual field deficit progressively improved. At 4 months
      after surgery, the patient's visual fields were normal. Therefore, an elongated
      ACA can compress the chiasm and result in a visual field deficit. In such
      circumstances when facing a progressive visual field deficit, microvascular
      decompression may improve vision.

PMID- 19852539
TI  - Induction of panic attack by stimulation of the ventromedial hypothalamus.
AB  - Panic attacks are sudden debilitating attacks of intense distress often
      accompanied by physical symptoms such as shortness of breath and heart
      palpitations. Numerous brain regions, hormones, and neurotransmitter systems are
      putatively involved, but the etiology and neurocircuitry of panic attacks is far
      from established. One particular brain region of interest is the ventromedial
      hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH
      has been shown to evoke an emotional "panic attack-like" escape behavior, and in
      humans, stimulation targeting nuclei just posterior or anterior to the VMH has
      reportedly induced panic attacks. The authors report findings obtained in an
      awake patient undergoing bilateral implantation of deep brain stimulation
      electrodes into the hypothalamus that strongly implicates the VMH as being
      critically involved in the genesis of panic attacks. First, as the stimulating
      electrode progressed deeper into the VMH, the intensity of stimulation required
      to evoke an attack systematically decreased; second, while stimulation of the VMH
      in either hemisphere evoked panic, stimulation that appeared to be in the center
      of the VMH was more potent. Thus, this evidence supports the role of the VMH in
      the induction of panic attacks purported by animal studies.

PMID- 19852541
TI  - Prevalence and impact of diffuse axonal injury in patients with moderate and
      severe head injury: a cohort study of early magnetic resonance imaging findings
      and 1-year outcome.
AB  - OBJECT: In this prospective cohort study the authors examined patients with
      moderate to severe head injuries using MR imaging in the early phase. The
      objective was to explore the occurrence of diffuse axonal injury (DAI) and
      determine whether DAI was related to level of consciousness and patient outcome.
      METHODS: One hundred and fifty-nine patients (age range 5-65 years) with
      traumatic brain injury, who survived the acute phase, and who had a Glasgow Coma
      Scale (GCS) score of 3-13 were admitted between October 2004 and August 2008. Of
      these 159 patients, 106 were examined using MR imaging within 4 weeks postinjury.
      Patients were classified into 1 of 3 stages of DAI: Stage 1, in which lesions
      were confined to the lobar white matter; Stage 2, in which there were callosal
      lesions; and Stage 3, in which lesions occurred in the dorsolateral brainstem.
      The outcome measure used 12 months postinjury was the Glasgow Outcome Scale
      Extended (GOSE). RESULTS: Diffuse axonal injury was detected in 72% of the
      patients and a combination of DAI and contusions or hematomas was found in 50%.
      The GCS score was significantly lower in patients with "pure DAI" (median GCS
      Score 9) than in patients without DAI (median GCS Score 12; p < 0.001). The GCS
      score was related to outcome only in those patients with DAI (r = 0.47; p =
      0.001). Patients with DAI had a median GOSE score of 7, and patients without DAI
      had a median GOSE score of 8 (p = 0.10). Outcome was better in patients with DAI
      Stage 1 (median GOSE Score 8) and DAI Stage 2 (median GOSE Score 7.5) than in
      patients with DAI Stage 3 (median GOSE Score 4; p < 0.001). Thus, in patients
      without any brainstem injury, there was no difference in good recovery between
      patients with DAI (67%) and patients without DAI (66%). CONCLUSIONS: Diffuse
      axonal injury was found in almost three-quarters of the patients with moderate
      and severe head injury who survived the acute phase. Diffuse axonal injury
      influenced the level of consciousness, and only in patients with DAI was GCS
      score related to outcome. Finally, DAI was a negative prognostic sign only when
      located in the brainstem.

PMID- 19852540
TI  - A prospective, randomized clinical trial to compare the effect of hyperbaric to
      normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen
      toxicity in severe traumatic brain injury.
AB  - OBJECT: Oxygen delivered in supraphysiological amounts is currently under
      investigation as a therapy for severe traumatic brain injury (TBI). Hyperoxia can
      be delivered to the brain under normobaric as well as hyperbaric conditions. In
      this study the authors directly compare hyperbaric oxygen (HBO2) and normobaric
      hyperoxia (NBH) treatment effects. METHODS: Sixty-nine patients who had sustained
      severe TBIs (mean Glasgow Coma Scale Score 5.8) were prospectively randomized to
      1 of 3 groups within 24 hours of injury: 1) HBO2, 60 minutes of HBO(2) at 1.5
      ATA; 2) NBH, 3 hours of 100% fraction of inspired oxygen at 1 ATA; and 3)
      control, standard care. Treatments occurred once every 24 hours for 3 consecutive
      days. Brain tissue PO(2), microdialysis, and intracranial pressure were
      continuously monitored. Cerebral blood flow (CBF), arteriovenous differences in
      oxygen, cerebral metabolic rate of oxygen (CMRO2), CSF lactate and F2-isoprostane
      concentrations, and bronchial alveolar lavage (BAL) fluid interleukin (IL)-8 and
      IL-6 assays were obtained pretreatment and 1 and 6 hours posttreatment. Mixed
      effects linear modeling was used to statistically test differences among the
      treatment arms as well as changes from pretreatment to posttreatment. RESULTS: In
      comparison with values in the control group, the brain tissue PO2 levels were
      significantly increased during treatment in both the HBO2 (mean +/- SEM, 223 +/-
      29 mm Hg) and NBH (86 +/- 12 mm Hg) groups (p < 0.0001) and following HBO2 until
      the next treatment session (p = 0.003). Hyperbaric O2 significantly increased CBF
      and CMRO2 for 6 hours (p < or = 0.01). Cerebrospinal fluid lactate concentrations
      decreased posttreatment in both the HBO2 and NBH groups (p < 0.05). The dialysate
      lactate levels in patients who had received HBO2 decreased for 5 hours
      posttreatment (p = 0.017). Microdialysis lactate/pyruvate (L/P) ratios were
      significantly decreased posttreatment in both HBO2 and NBH groups (p < 0.05).
      Cerebral blood flow, CMRO2, microdialysate lactate, and the L/P ratio had
      significantly greater improvement when a brain tissue PO2 > or = 200 mm Hg was
      achieved during treatment (p < 0.01). Intracranial pressure was significantly
      lower after HBO2 until the next treatment session (p < 0.001) in comparison with
      levels in the control group. The treatment effect persisted over all 3 days. No
      increase was seen in the CSF F2-isoprostane levels, microdialysate glycerol, and
      BAL inflammatory markers, which were used to monitor potential O2 toxicity.
      CONCLUSIONS: Hyperbaric O2 has a more robust posttreatment effect than NBH on
      oxidative cerebral metabolism related to its ability to produce a brain tissue
      PO2 > or = 200 mm Hg. However, it appears that O2 treatment for severe TBI is not
      an all or nothing phenomenon but represents a graduated effect. No signs of
      pulmonary or cerebral O2 toxicity were present.

PMID- 19852542
TI  - Preoperative evaluation of neurovascular relationships for microvascular
      decompression in the cerebellopontine angle in a virtual reality environment.
AB  - OBJECT: In this paper the authors' goal was to evaluate the feasibility and
      efficacy of a virtual reality (VR) system in preoperative planning for
      microvascular decompression (MVD) procedures treating idiopathic trigeminal
      neuralgia and hemifacial spasm. The system's role in surgical simulation and
      training was also assessed. METHODS: Between May 2008 and April 2009, the authors
      used the Dextroscope system to visualize the neurovascular complex and simulate
      MVD in the cerebellopontine angle in a VR environment in 16 patients (6 patients
      had trigeminal neuralgia and 10 had hemifacial spasm). Reconstructions were
      carried out 2-3 days before MVD. Images were printed in a red-blue stereoscopic
      format for teaching and discussion and were brought into the operating room to be
      compared with real-time intraoperative findings. RESULTS: The VR environment was
      a powerful aid for spatial understanding of the neurovascular relationship in MVD
      for operating surgeons and trainees. Through an initial series of
      comparison/confirmation experiences, the senior neurosurgeon became accustomed to
      the system. He could predict intraoperative problems and simulate surgical
      maneuvering, which increased his confidence in performing the procedure.
      CONCLUSIONS: The Dextroscope system is an easy and rapid method to create a
      stereoscopic neurovascular model for MVD that is highly concordant with
      intraoperative findings. It effectively shortens the learning curve and adds to
      the surgeon's confidence.

PMID- 19852543
TI  - Toll-like receptor 4 expression during cerebral aneurysm formation. Laboratory
      investigation.
AB  - OBJECT: The pathophysiological origin of cerebral aneurysms is closely associated
      with chronic inflammation in arterial walls. Recently, the authors identified
      nuclear factor-kappa B (NF-kappaB) as a key mediator of cerebral aneurysm
      formation and progression. Because Toll-like receptor 4 (TLR4) stimulates NF
      kappaB activation in arterial walls in atherosclerosis, the authors hypothesize
      that TLR4 expresses in cerebral aneurysms and contributes to the activation of NF
      kappaB in cerebral aneurysm walls. METHODS: Cerebral aneurysms were induced in
      male Sprague-Dawley rats. Expression of TLRs in cerebral aneurysm walls was
      assessed using reverse transcriptase polymerase chain reaction (RT-PCR). The
      expression of TLR4 was examined using RT-PCR, immunohistochemical studies, and
      Western blotting. To assess TLR4 dependency on NF-kappaB activation, double
      immunostaining and a study using NF-kappaB-deficient mice were done. Finally,
      TLR4 expression in human cerebral aneurysm walls was assessed using
      immunohistochemical studies. RESULTS: In cerebral aneurysm walls, TLR1, -4, -5, 
      6, -10, and -11 were expressed. Among them, TLR4 and TLR10 expression changed
      during cerebral aneurysm formation. Expression of TLR4 was predominantly in the
      endothelial cell layer of cerebral aneurysm walls, and was transitionally
      upregulated at the early stage of cerebral aneurysm formation. The TLR4
      expression coincided well with NF-kappaB activation. In human cerebral aneurysms,
      TLR4 was also expressed in the endothelial cell layer, as it was in rats.
      CONCLUSIONS: Toll-like receptor 4 was expressed in cerebral aneurysm walls both
      in rats and humans. This receptor may play a crucial role in cerebral aneurysm
      formation through NF-kappaB activation in endothelial cells. The results of the
      present study will shed new light on the pathogenesis of cerebral aneurysm
      formation.

PMID- 19852544
TI  - Embolization of middle cerebral artery aneurysms: ready for prime time?

PMID- 19852545
TI  - Gamma Knife radiosurgery for trigeminal neuralgia: the impact of magnetic
      resonance imaging-detected vascular impingement of the affected nerve.
AB  - OBJECT: Trigeminal neuralgia is believed to be related to vascular compression of
      the affected nerve. Radiosurgery has been shown to be reasonably effective for
      treatment of medically refractory trigeminal neuralgia. This study explores the
      rate of occurrence of MR imaging-demonstrated vascular impingement of the
      affected nerve and the extent to which vascular impingement affects pain relief
      in a population of trigeminal neuralgia patients undergoing Gamma Knife
      radiosurgery (GKRS). METHODS: The authors performed a retrospective analysis of
      106 cases involving patients treated for typical trigeminal neuralgia using GKRS.
      Patients with or without single-vessel impingement on CISS MR imaging sequences
      and with no previous surgery were included in the study. Pain relief was assessed
      according to the Barrow Neurological Institute (BNI) pain intensity score at the
      last follow-up. Degree of impingement, nerve diameter preand post-impingement,
      isocenter placement, and dose to the point of maximum impingement were evaluated
      in relation to the improvement of BNI score. RESULTS: The overall median follow
      up period was 31 months. Overall, a BNI pain score of 1 was achieved in 59.4% of
      patients at last follow-up. Vessel impingement was seen in 63 patients (59%).
      There was no significant difference in pain relief between those with and without
      vascular impingement following GKRS (p > 0.05). In those with vascular
      impingement on MR imaging, the median fraction of vessel impingement was 0.3
      (range 0.04-0.59). The median dose to the site of maximum impingement was 42 Gy
      (range 2.9-79 Gy). Increased dose (p = 0.019) and closer proximity of the
      isocenter to the site of maximum vessel impingement (p = 0.012) correlated in a
      statistically significant fashion with improved BNI scores in those demonstrating
      vascular impingement on the GKRS planning MR imaging. CONCLUSIONS: Vascular
      impingement of the affected nerve was seen in the majority of patients with
      trigeminal neuralgia. Overall pain relief following GKRS was comparable in those
      with and without evidence of vascular compression on MR imaging. In subgroup
      analysis of those with MR imaging evidence of vessel impingement of the affected
      trigeminal nerve, pain relief correlated with a higher dose to the point of
      contact between the impinging vessel and the trigeminal nerve. Such a finding may
      point to vascular changes affording at least some degree of relief following GKRS
      for trigeminal neuralgia.

PMID- 19852546
TI  - Hyperbaric oxygen therapy.

PMID- 19852548
TI  - Source category-specific PM2.5 and urinary levels of Clara cell protein CC16. The
      ULTRA study.
AB  - INTRODUCTION: We have previously reported that outdoor levels of fine particles
      (PM(2.5), diameter <2.5 microm) are associated with urinary CC16, a marker for
      lung damage, in Helsinki, Finland, but not in the other two ULTRA cities
      (Amsterdam, The Netherlands, and Erfurt, Germany). We here evaluated whether
      PM(2.5) from specific source categories would be more strongly associated with
      CC16 than (total) PM(2.5). In addition, we compared two source apportionment
      methods. METHODS: We collected biweekly spot urinary samples over 6 months from
      121 subjects with coronary heart disease for the determination of CC16 (n =
      1251). Principal component analysis (PCA) was used to apportion daily outdoor
      PM(2.5) between different source categories. In addition, the multilinear engine
      (ME) was used for the source apportionment in Amsterdam and Helsinki. We analyzed
      associations of source category-specific PM(2.5) and PM(2.5) absorbance, an
      indicator for combustion originating particles, with logarithmized values of CC16
      adjusting for urinary creatinine using multivariate mixed models in STATA.
      RESULTS: In the pooled analyses, CC16 was increased by 0.6% (standard error 0.3%)
      per 1 x 10(-5) m(-1) increase in the same-day levels of PM(2.5) absorbance.
      Source category-specific PM(2.5) concentrations were not consistently associated
      with the levels of CC16 in the three cities. Correlations between source category
      specific PM(2.5) determined using either PCA or ME were in general high.
      Associations of source category-specific PM(2.5) with CC16 in Amsterdam and
      Helsinki were statistically less significant when ME was used. CONCLUSIONS: The
      present results suggest that PM(2.5) from combustion sources increases epithelial
      barrier permeability in lungs.

PMID- 19852549
TI  - Determination of carboxyhaemoglobin in humans following low-level exposures to
      carbon monoxide.
AB  - This study proposes to estimate carboxyhaemoglobin (COHb) levels in the blood of
      men and women of various ages exposed to common concentrations of carbon monoxide
      (CO) using a model with only one free parameter while integrating alveoli-blood
      and blood-tissue CO exchanges. The model retained is essentially that of Coburn
      et al. (1965) with two important additions: an alveoli compartment for the
      dynamics of CO exchanges between alveoli and blood, and a compartment for the
      significant amounts of CO bound to heme proteins in extravascular spaces. The
      model was validated by comparing its simulations with various published data sets
      for the COHb time profiles of volunteers exposed to known CO concentrations. Once
      the model was validated, it was used to simulate various situations of interest
      for their impact on public health. This approach yields reliable estimations of
      the time profiles of COHb levels resulting from different levels of CO exposure
      over various periods of time and under various conditions (resting, exercise,
      working, and smoking). The non-linear kinetics of CO, observed experimentally,
      were correctly reproduced by simulations with the model. Simulations were also
      carried out iteratively to determine the exposure times and CO concentrations in
      ambient air needed to reach the maximum levels of COHb recommended by Health
      Canada, the U.S. Environmental Protection Agency (EPA), and the World Health
      Organisation (WHO) for each age group of the general population. The lowest CO
      concentrations leading to maximum COHb levels of 1.5, 2, and 2.5% were
      determined.

PMID- 19852547
TI  - Effect of diesel exhaust inhalation on antioxidant and oxidative stress responses
      in adults with metabolic syndrome.
AB  - BACKGROUND: Traffic-related air pollution is associated with cardiovascular
      morbidity and mortality. Although the biological mechanisms are not well
      understood, oxidative stress may be a primary pathway. Subpopulations, such as
      individuals with metabolic syndrome (MeS), may be at increased risk of adverse
      effects associated with air pollution. Our aim was to assess the relationship
      between exposure to diesel exhaust (DE) and indicators of systemic antioxidant
      and oxidative responses in adults with MeS. We hypothesized that DE exposure
      would result in greater oxidative stress and antioxidant responses compared with
      filtered air (FA). METHODS: Ten adult subjects with MeS were exposed on separate
      days for two hours to FA or DE (at 200microg/m3), in a double blind, crossover
      experiment. Urinary 8-isoPGF2alpha (F2-isoprostanes), and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) were assessed as markers of oxidative stress at 3 hrs and
      22 hrs, respectively, after exposure initiation. To assess the short-term
      antioxidant response we analyzed plasma ascorbic acid (AA) 90 minutes after
      exposure initiation. All outcomes were compared to pre-exposure levels, and mean
      changes were compared between FA and DE exposures. RESULTS: Mean changes in
      urinary F2-isoprostanes (ng/mg creatinine), (-0.05 [95% CI = -0.29, 0.15]), and 8
      OHdG (microg/g creatinine) (-0.09 [-0.13, 0.31]), were not statistically
      significant. Mean changes in plasma AA (mg/dl) were also not significant (-0.02 [
      0.78, 0.04]). CONCLUSIONS: In this carefully controlled experiment, we did not
      detect significant changes in oxidative stress or systemic antioxidant responses
      in subjects with MeS exposed to 200microg/m3 DE.

PMID- 19852550
TI  - Air pollution and hospital admissions for pneumonia: are there potentially
      sensitive groups?
AB  - Recent studies have shown that air pollution is a risk factor for hospitalization
      for pneumonia. However, there is limited evidence to suggest what subpopulations
      are at greater risk from air pollution. This study was undertaken to examine the
      modifying effect of specific secondary diagnosis (including hypertension,
      diabetes, asthma, and upper respiratory infections) on the relationship between
      hospital admissions for pneumonia and ambient air pollutants. Hospital admissions
      for pneumonia and ambient air pollution data for Kaohsiung were obtained for the
      period 1996-2006. The relative risk of hospital admission was estimated using a
      case-crossover approach. We found that an interquartile range (IQR) increase in
      PM(10), NO(2), and CO on warm days was associated with a 28% (95% confidence
      interval [CI], 11-48%), 40% (95% CI, 20-63%), and 31% (95% CI, 19-45%),
      respectively, increase in admissions for pneumonia with upper respiratory
      infections (URI), but only 23% (95% CI, 18-28%), 30% (95% CI, 25-36%), and 24%
      (95% CI, 21-28%), respectively, increase for persons without URI. An IQR increase
      in PM(10), SO(2), and CO on cool days was associated with a 70% (95% CI, 50-92%),
      30% (95% CI, 15-47%), and 64% (95% CI, 47-83%), respectively, increase in
      admissions in persons with URI, and an increase of 64% (95% CI, 57-70%), 18% (95%
      CI, 14-22%), and 55% (95% CI, 50-60%), respectively, in admissions in persons
      without URI. Our findings provide evidence that patients with comorbid URI may
      increase the risk of hospital admissions for pneumonia, in relation to air
      pollutant levels.

PMID- 19852551
TI  - Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis
      sativa.
AB  - Cannabis sativa is a well-known recreational drug and, as such, a controlled
      substance of which possession and use are illegal in most countries of the world.
      Due to the legal constraints on the possession and use of C. sativa, relatively
      little research on the medicinal qualities of this plant has been conducted.
      Interest in the medicinal uses of this plant has, however, increased in the last
      decades. The methods of administration for medicinal purposes are mainly through
      oral ingestion, smoking, and nowadays also inhalation through vaporization.
      During this study the commercially available Volcano vaporizing device was
      compared with cannabis cigarette smoke. The cannabis smoke and vapor (obtained at
      different temperatures) were quantitatively analyzed by high-performance liquid
      chromatography (HPLC). In addition, different quantities of cannabis material
      were also tested with the vaporizer. The cannabinoids:by-products ratio in the
      vapor obtained at 200 degrees C and 230 degrees C was significantly higher than
      in the cigarette smoke. The worst ratio of cannabinoids:by-products was obtained
      from the vaporized cannabis sample at 170 degrees C.

PMID- 19852552
TI  - Air pollution and emergency room visits for cardiac arrhythmia in a subtropical
      city: Taipei, Taiwan.
AB  - This study was undertaken to determine whether there was an association between
      air pollutant levels and emergency room (ER) visits for cardiac arrhythmia in
      Taipei, Taiwan. ER visits for cardiac arrhythmia and ambient air pollution data
      for Taipei were obtained for the period 2000-2006. The relative risk of ER visits
      was estimated using a case-crossover approach, controlling for weather variables,
      day of the week, seasonality, and long-term time trends. In the single-pollutant
      model, on warm days (> or =23 degrees C), statistically significant positive
      associations were found for all pollutants except SO(2). On cool days (<23
      degrees C), all pollutants were also significantly associated with the number of
      ER visits for cardiac arrhythmia, except SO(2). For the two-pollutant model,
      results for O(3) and NO(2) remained statistically significant on both warm and
      cool days. This study provides evidence that higher levels of ambient air
      pollutants increase the risk of ER visits for cardiac arrhythmia.

PMID- 19852553
TI  - Histopathological changes of the nasal mucosa induced by smoking.
AB  - Changes in the histopathology of the respiratory epithelium in response to
      cigarette smoking have been studied in depth in the lungs, but data on the nasal
      lining are lacking. The aim of the present retrospective study was to investigate
      the histological changes that occur in the nasal mucosa of smokers compared with
      non-smokers. The study group included 47 patients who underwent partial resection
      of the inferior turbinates. Archival nasal tissue samples were collected and
      examined by light microscopy: the number of goblet cells was counted, and the
      degree of inflammation, congestion, and edema was graded as mild, moderate, or
      severe. Epithelial thickness was measured as well. Findings were compared between
      smokers (n = 21) and non-smokers (n = 26). On statistical analysis, significant
      differences were found between the smokers and non-smokers in mean number of
      goblet cells in the nasal epithelium, 43.43 +/- 16.80 vs. 16.23 +/- 5.65
      respectively (p < 0.0001), mean edema grade, 2.43 +/- 0.75 vs. 1.12 +/- 0.33
      respectively (p < 0.0001), and mean epithelial thickness, 111.9 +/- 25.8 microm
      vs. 60.4 +/- 18.4 microm respectively (p < 0.0001). The corresponding mean values
      of congestion were 2 +/- 0.71 and 1.27 +/- 0.67 (p < 0.001), and of inflammation,
      1.81 +/- 0.60 and 1.81 +/- 0.85 (NS). In conclusion, the histopathological
      findings in the nasal mucosa of smokers resemble reported findings in the
      bronchial respiratory epithelium. The main differences from non-smokers are
      greater goblet cell hyperplasia and thicker epithelium.

PMID- 19852554
TI  - Acute airway effects of diacetyl in mice.
AB  - Occupational exposures to the butter flavouring agent diacetyl (2,3-butanedione)
      have caused lung inflammation and severe airflow limitation due to bronchiolitis
      obliterans. Diacetyl is naturally present in butter, beer, white wine, etc., and
      its pleasant odour is easily recognized by consumers. However, this pleasant
      odour may induce a false sense of safety when higher airborne concentrations are
      encountered in industrial use. In this study, the acute warning properties, in
      terms of sensory irritation, that could be useful to prevent workers from
      exposures to a high concentration were first investigated in a mouse bioassay.
      Then at higher exposure concentrations, the possibility of airflow limitation and
      pulmonary irritation were studied with the same mouse bioassay. Diacetyl induces
      concentration-dependent irritation in all parts of the respiratory tract during a
      2-h exposure period. The no-observed-effect levels for each effect in the mice
      were above 100 ppm and initiation of sensory irritation in humans was estimated
      to occur above 20 ppm. No acute warning signal from the airways is expected at
      diacetyl levels that have caused bronchiolitis obliterans and other toxic
      effects. The sensory irritation effect, which occurred rapidly upon initiation of
      exposure, faded rapidly. Furthermore, high-level diacetyl exposures decreased the
      sensory irritation warning signal in mice upon repeated exposure, which suggests
      that the compound is especially insidious.

PMID- 19852555
TI  - Effect of pre- and postnatal exposure to urban air pollution on myocardial lipid
      peroxidation levels in adult mice.
AB  - Exposure to air pollution can elicit cardiovascular health effects. Children and
      unborn fetuses appear to be particularly vulnerable. However, the mechanisms
      involved in cardiovascular damage are poorly understood. It has been suggested
      that the oxidative stress generated by air pollution exposure triggers tissue
      injury. To investigate whether prenatal exposure can enhance oxidative stress in
      myocardium of adult animals, mice were placed in a clean chamber (CC, filtered
      urban air) and in a polluted chamber (PC, Sao Paulo city) during the gestational
      period and/or for 3 mo after birth, according to 4 protocols: control group
      prenatal and postnatal life in CC; prenatal group-prenatal in PC and postnatal
      life in CC; postnatal group-prenatal in CC and postnatal life in PC; and pre-post
      group-prenatal and postnatal life in PC. As an indicator of oxidative stress,
      levels of lipid peroxidation in hearts were measured by malondialdehyde (MDA)
      quantification and by quantification of the myocardial immunoreactivity for 15
      F2t-isoprostane. Ultrastructural studies were performed to detect cellular
      alterations related to oxidative stress. Concentration of MDA was significantly
      increased in postnatal (2.45 +/- 0.84 nmol/mg) and pre-post groups (3.84 +/- 1.39
      nmol/mg) compared to the control group (0.31 +/- 0.10 nmol/mg) (p < .01). MDA
      values in the pre-post group were significantly increased compared to the
      prenatal group (0.71 +/- 0.15 nmol/mg) (p = .017). Myocardial isoprostane area
      fraction in the pre-post group was increased compared to other groups (p < or =
      .01). Results show that ambient levels of air pollution elicit cardiac oxidative
      stress in adult mice, and that gestational exposure may enhance this effect.

PMID- 19852556
TI  - A cross-sectional investigation of biomarkers of risk after a decade of smoking.
AB  - Two groups of 20 healthy volunteers with cigarettes of different tar yield were
      compared with a group of 20 never smokers over 24 h for several biomarkers. All
      groups were of similar mean ages and the smokers had smoked for a homogeneous
      period of approximately 10 yr. The groups were assessed using routine medical
      parameters as well as biomarkers of recent smoke exposure and other biomarkers
      that were under evaluation as possible markers of risk for smoking-associated
      diseases. All biomarkers of exposure-carbon monoxide, nicotine plus its five
      major metabolites, and 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol (NNAL)-were
      significantly elevated in smokers. For biomarkers of potential risk evaluated in
      the blood, white cells and immunoglobulin (Ig) G showed a decrease related to
      smoking status (p < .01). Interleukin 6 levels were higher in smoker groups
      compared to never smokers, with a significant increasing trend across the groups
      (p < .05). Among the urinary biomarkers studied, 11-deydro-thromboxane B2, 2,3
      dinor-thromboxane B2, and thymidine glycol showed significant increasing trends
      across the groups (p < .01). The results suggest that after the first decade or
      less of smoking, changes in inflammatory, immunological, and cardiovascular
      function can be observed. However, further studies on larger groups will be
      required to better understand the kinetics of these subtle effects observed early
      in smokers and their relationship with the potential risk of subsequent smoking
      associated disease.

PMID- 19852557
TI  - A new tool for the early diagnosis of carbon monoxide intoxication.
AB  - Invasive measurement of carboxyhemoglobin (COHb) by blood gas analysis (BGA) is
      accepted as the standard diagnostic procedure in diagnosis of inhalation injury
      and carbon monoxide (CO) intoxications. The main disadvantage of BGA with COHb
      testing is the unavailability in pre-hospital rescue conditions. The non-invasive
      SpCO analysis using pulse CO oximetry (Rad57, Masimo Corp., USA) represents an
      easy-to-handle device to facilitate the diagnosis of CO intoxication. Between
      January 2006 and August 2008, 20 patients who were admitted with CO intoxication
      to our burn centre were included in this study. Blood gas analysis including COHb
      testing was performed on the first day, hourly. At the same time, SpCO was
      determined using the Rad57 pulse CO oximeter. Patients received inhalative oxygen
      according to the parameters of blood gas analysis or hyperbaric oxygenation if
      COHb > 10%. Five young healthy volunteers served as control group. The SpCO of
      the volunteers was cross-checked against their COHb levels, which were measured
      by blood gas analysis. Results of pulse CO oximetry revealed a mean error of
      approximately 3.15% from the results achieved by blood gas analysis. If COHb
      resulted in values higher than 10%, the bias remained approximately the same
      (3.43%/precision 2.362%). When different blood gas analyzers in our department
      were tested with the same patient sample, a mean error of 2.4% was found. This is
      only 1% lower compared to the mean error of pulse CO oximetry. Therefore, pulse
      CO oximetry represents a reliable measurement technique that is easy to handle
      and could facilitate the early diagnosis of CO intoxication in pre-hospital
      rescue conditions.

PMID- 19852558
TI  - Comparison of two in vitro models of cigarette smoke exposure.
AB  - Cigarette smoke is associated with a high morbidity and mortality, and affects
      particularly the respiratory tract. Various in vitro models have been developed
      to study the effects of cigarette smoke on bronchial epithelial cells. To
      identify an adequate exposure model of cigarette smoke, we analysed the effects
      of cigarette smoke extract (CSE) and a smoking chamber on bronchial epithelial
      cells. The release of monocyte chemoattractant protein (MCP)-1, interleukin (IL)
      10, and vascular endothelial growth factor (VEGF) was measured. Bronchial
      epithelial cells isolated from Sprague-Dawley rat (NRBE) were exposed to 3% CSE
      or air control every day for 3 days. In the second model, NRBE were placed in an
      air/liquid interface and exposed, in a smoking chamber, to whole smoke from 2
      cigarettes, twice daily for 3 days. Levels of MCP-1, IL-10, and VEGF were
      measured by enzyme-linked immunosorbent assay (ELISA), 24 h after the last
      exposure. The pattern of MCP-1 production by bronchial epithelial cells was
      different between the two models. MCP-1 release was increased after 3 days of
      exposure in the CSE model, but was inhibited using the smoking chamber model.
      Production of IL-10 by NRBE was reduced after 3 days in both models. Finally, no
      difference was observed in the production of VEGF between the two models. CSE and
      the smoking chamber differently modulate bronchial epithelial cell mediator
      production, demonstrating that the model of cigarette smoke exposure used can
      influence the data obtained.

PMID- 19852559
TI  - Meta-analysis of nitrogen dioxide exposure and airway hyper-responsiveness in
      asthmatics.
AB  - The effects of 0.1 to 0.6 ppm nitrogen dioxide (NO2) on airway hyper
      responsiveness (AHR) to airway challenges in asthmatics have been evaluated in
      several controlled exposure studies. The authors conducted meta-analyses and meta
      regressions of these studies using several effect measures for AHR: a change (in
      NO2 versus air) in (1) the provocative dose of a challenge agent necessary to
      cause a specified change in lung function (PD), (2) the change in FEV1 after an
      airway challenge, and (3) the fraction of subjects with increased AHR. Although
      several effect estimates from the meta-analyses are statistically significant,
      they are all so small that they are not likely to be clinically relevant. More
      importantly, there are no exposure-response associations for any effect estimates
      based on linear meta-regressions or analyses of effect estimates for exposure
      groups (0.1 to <0.2 ppm, 0.2 to <0.3 ppm, etc.). This is also generally the case
      for analyses stratified by airway challenge (specific/nonspecific), exposure
      method (mouthpiece/whole chamber), and activity during exposure (rest/exercise).
      The results of these analyses indicate that, to the extent the effects observed
      are associated with NO2 exposure, they are sufficiently small such that they do
      not provide evidence that NO2 has a significant adverse effect on AHR at
      concentrations up to 0.6 ppm.

PMID- 19852560
TI  - Critical review of the human data on short-term nitrogen dioxide (NO2) exposures:
      evidence for NO2 no-effect levels.
AB  - Nitrogen dioxide (NO2) is a ubiquitous atmospheric pollutant due to the
      widespread prevalence of both natural and anthropogenic sources, and it can be a
      respiratory irritant when inhaled at elevated concentrations. Evidence for health
      effects of ambient NO2 derives from three types of studies: observational
      epidemiology, human clinical exposures, and animal toxicology. Our review focuses
      on the human clinical studies of adverse health effects of short-term NO2
      exposures, given the substantial uncertainties and limitations in interpretation
      of the other lines of evidence. We examined more than 50 experimental studies of
      humans inhaling NO2, finding notably that the reporting of statistically
      significant changes in lung function and bronchial sensitivity did not show a
      consistent trend with increasing NO2 concentrations. Functional changes were
      generally mild and transient, the reported effects were not uniformly adverse,
      and they were not usually accompanied by NO2-dependent increases in symptoms. The
      available human clinical results do not establish a mechanistic pathway leading
      to adverse health impacts for short-term NO2 exposures at levels typical of
      maximum 1-h concentrations in the present-day ambient environment (i.e., below
      0.2 ppm). Our review of these data indicates that a health-protective, short-term
      NO2 guideline level for susceptible (and healthy) populations would reflect a
      policy choice between 0.2 and 0.6 ppm. EXTENDED ABSTRACT: Nitrogen dioxide (NO2)
      is a ubiquitous atmospheric pollutant due to the widespread prevalence of both
      natural and anthropogenic sources, and it can be a respiratory irritant when
      inhaled at elevated concentrations. Natural NO2 sources include volcanic action,
      forest fires, lightning, and the stratosphere; man-made NO2 emissions derive from
      fossil fuel combustion and incineration. The current National Ambient Air Quality
      Standard (NAAQS) for NO2, initially established in 1971, is 0.053 ppm (annual
      average). Ambient concentrations monitored in urban areas in the United States
      are approximately 0.015 ppm, as an annual mean, i.e., below the current NAAQS.
      Short-term (1-h peak) NO2 concentrations outdoors are not likely to exceed 0.2
      ppm, and even 1-h periods exceeding 0.1 ppm are infrequent. Inside homes, 1-h NO2
      peaks, typically arising from gas cooking, can range between 0.4 and 1.5 ppm. The
      health effects evidence of relevance to ambient NO2 derives from three lines of
      investigation: epidemiology studies, human clinical studies, and animal
      toxicology studies. The NO2 epidemiology remains inconsistent and uncertain due
      to the potential for exposure misclassification, residual confounding, and co
      pollutant effects, whereas animal toxicology findings using high levels of NO2
      exposure require extrapolation to humans exposed at low ambient NO2 levels. Given
      the limitations and uncertainties in the other lines of health effects evidence,
      our review thus focused on clinical studies where human volunteers (including
      asthmatics, children, and elderly) inhaled NO2 at levels from 0.1 to 3.5 ppm
      during short-term ((1/2)-6-h) exposures, often combined with exercise, and
      occasionally combined with co-pollutants. We examined the reported biological
      effects and classified them into (a) lung immune responses and inflammation, (b)
      lung function changes and airway hyperresponsiveness (AHR), and (c) health
      effects outside the lungs (extrapulmonary). We examined more than 50 experimental
      studies of humans inhaling NO2, finding that such clinical data on short-term
      exposure allowed discrimination of NO2 no-effect levels versus lowest-adverse
      effects levels. Our conclusions are summarized by these six points: For lung
      immune responses and inflammation: (1) healthy subjects exposed to NO2 below 1
      ppm do not show pulmonary inflammation; (2) at 2 ppm for 4 h, neutrophils and
      cytokines in lung-lavage fluid can increase, but these changes do not necessarily
      correlate with significant or sustained changes in lung function; (3) there is no
      consistent evidence that NO2 concentrations below 2 ppm increase susceptibility
      to viral infection; (4) for asthmatics and individuals having chronic obstructive
      pulmonary disease (COPD), NO2-induced lung inflammation is not expected below 0.6
      ppm, although one research group reported enhancement of proinflammatory
      processes at 0.26 ppm. With regard to NO2-induced AHR: (5) studies of responses
      to specific or nonspecific airway challenges (e.g., ragweed, methacholine)
      suggest that asthmatic individuals were not affected by NO2 up to about 0.6 ppm,
      although some sensitive subsets may respond to levels as low as 0.2 ppm. And
      finally, for extra-pulmonary effects: (6) such effects (e.g., changes in blood
      chemistry) generally required NO2 concentrations above 1-2 ppm. Overall, our
      review of data from experiments with humans indicates that a health-protective,
      short-term-average NO2 guideline level for susceptible populations (and healthy
      populations) would reflect a policy choice between 0.2 and 0.6 ppm. The available
      human clinical results do not establish a mechanistic pathway leading to adverse
      health impacts for short-term NO2 exposures at levels typical of maximum 1-h
      concentrations in the present-day ambient environment (i.e., below 0.2 ppm).

PMID- 19852561
TI  - Trichloroethylene risk assessment: a review and commentary.
AB  - Trichloroethylene (TCE) is a widespread environmental contaminant that is
      carcinogenic when given in high, chronic doses to certain strains of mice and
      rats. The capacity of TCE to cause cancer in humans is less clear. The current
      maximum contaminant level (MCL) of 5 ppb (microg/L) is based on an US Environment
      Protection Agency (USEPA) policy decision rather than the underlying science. In
      view of major advances in understanding the etiology and mechanisms of chemically
      induced cancer, USEPA began in the late 1990s to revise its guidelines for cancer
      risk assessment. TCE was chosen as the pilot chemical. The USEPA (2005) final
      guidelines emphasized a "weight-of-evidence" approach with consideration of dose
      response relationships, modes of action, and metabolic/toxicokinetic processes.
      Where adequate data are available to support reversible binding of the
      carcinogenic moiety to biological receptors as the initiating event (i.e., a
      threshold exists), a nonlinear approach is to be used. Otherwise, the default
      assumption of a linear (i.e., nonthreshold) dose-response is utilized. When
      validated physiologically based pharmacokinetic (PBPK) models are available, they
      are to be used to predict internal dosimetry as the basis for species and dose
      extrapolations. The present article reviews pertinent literature and discusses
      areas where research may resolve some outstanding issues and facilitate the
      reassessment process. Key research needs are proposed, including role of
      dichloroacetic acid (DCA) in TCE-induced liver tumorigenesis in humans; extension
      of current PBPK models to predict target organ deposition of trichloroacetic acid
      (TCA) and DCA in humans ingesting TCE in drinking water; use of human hepatocytes
      to ascertain metabolic rate constants for use in PBPK models that incorporate
      variability in metabolism of TCE by potentially sensitive subpopulations;
      measurement of the efficiency of first-pass elimination of trace levels of TCE in
      drinking water; and assessment of exogenous factors' (e.g., alcohol, drugs)
      ability to alter metabolic activation and risks at such low-level exposure.

PMID- 19852562
TI  - A review of health effects of carbon disulfide in viscose industry and a proposal
      for an occupational exposure limit.
AB  - Occupational exposure limits (OELs) for carbon disulfide vary between 1 and 10
      ppm worldwide. They are generally based on health effects observed in viscose
      industry. Publications after the mid-1970s are reviewed to determine whether
      there is a scientific justification for an OEL below 10 ppm. The exposure
      situation in viscose industry is governed by long exposure durations, high
      exposures in past decades, high peak exposures, former analytical procedures
      underestimating exposure, and shift work. Three approaches were used to define an
      OEL based on workplace data: (1) Division of a cumulative exposure index by
      lifetime exposure duration. This approach ignores the possible existence of a
      threshold and fails to differentiate between brief high and sustained low
      exposures. (2) Defining the NOEL/LOEL by mean exposure levels. With a wide range
      of exposures, effects observed at the mean are driven by high exposures
      underestimating the true NOEL. (3) Assessment of effects observed at workplaces
      complying with a predefined exposure limit. Without adverse effects at such a
      limit this should be the starting point to define the OEL. The most important
      health effects for carbon disulfide are coronary heart disease, coronary risk
      factors, retinal angiopathy, color discrimination, effects on peripheral nerves,
      psychophysiological effects, morphological and other central nervous system (CNS)
      effects, and fertility and hormonal effects. The data generally support an OEL of
      10 ppm. Some uncertainties exist for effects on electrocardiogram (ECG), heart
      rate, retinal microaneurysms (in Japanese workers), peripheral nerve conduction
      velocities, some psychophysiological parameters, brain magnetic resonance imaging
      (MRI; hyperintensive spots), and hearing function. Further investigations on
      workers under defined long-term exposure conditions might help to come to a final
      conclusion. Finally, the reproductive capacity of female workers may not be
      adequately protected at exposures around 10 ppm.

PMID- 19852563
TI  - Abstracts of the 5th Congress of the Asia Pacific Society for the Study of Aging
      Male (APSSAM), in conjunction with the 9th Annual Meeting of the Japanese Society
      of Men's Health (JSMH) and the 4th Japan-ASEAN Men's Health & Aging Conference.
      October 15-18, 2009. Osaka, Japan.

PMID- 19852565
TI  - The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer.
AB  - BACKGROUND: The p38 mitogen-activated protein kinase (MAPK) is activated by
      various pro-inflammatory and stressful stimuli. Mounting evidence suggests that
      the p38 MAPK signaling cascade is involved in various biological responses other
      than inflammation such as cell proliferation, differentiation, apoptosis and
      invasion, suggesting that the p38 MAPK can serve as a potential therapeutic
      target for the treatment of not only inflammatory diseases but also cancer.
      METHODS: The unique characteristics of p38 MAPK are summarized with regard to
      activation and function of p38 MAPK signaling cascades. We then discuss the
      involvement of p38 MAPK in diseases and the implications of the possible
      therapeutic use of p38 MAPK inhibitors. The p38 MAPK inhibitors that have been
      used in the in vitro/in vivo systems as well as in the clinical trials are
      summarized. RESULTS/CONCLUSION: The p38 MAPK plays an important role in key
      cellular processes related to inflammation and cancer. Understanding the signal
      transduction mechanisms and gene regulation by p38 MAPK provides useful
      information in the development of p38 MAPK inhibitors with therapeutic benefits
      with reduced side effects. In this review, we summarize and present the list of
      p38 MAPK inhibitors in in vitro/in vivo studies as well as in clinical trials.

PMID- 19852566
TI  - Monotherapy versus combination therapy for the treatment of chronic hepatitis B.
AB  - BACKGROUND: Nucleos(t)ide analogues, active against hepatitis B polymerase,
      suppress viral replication and improve clinical outcome. However, the emergence
      of drug-resistant mutants can result in treatment failure. OBJECTIVES: We
      describe how the choice of first-line therapy is critical to long-term treatment
      success. METHODS: A review of current drug therapies is provided.
      RESULTS/CONCLUSIONS: Monotherapy with early-generation drugs (lamivudine or
      adefovir) was associated with a high rate of viral drug resistance and
      combination therapy with these agents was shown to reduce the incidence of
      resistance. The latest-generation drugs (entecavir and tenofovir) are potent
      inhibitors of viral replication and, in treatment-naive subjects, viral
      resistance to entecavir is uncommon and is not yet reported to tenofovir.
      Therefore, monotherapy with either entecavir or tenofovir is the current
      preferred option in treatment-naive patients. Combination therapy is appropriate
      in those with drug-resistant HBV infection, where drug choice is guided by the
      viral drug-resistance genotype/phenotype. Although combination therapy has been
      advocated in other patient groups (e.g., those with decompensated cirrhosis and
      following liver transplantation), there are, as yet, no data to mandate the use
      of combination therapy in such patients and any perceived benefit must be weighed
      against increased cost and risk for toxicity.

PMID- 19852567
TI  - Discontinued drugs 2008: pulmonary and allergy.
AB  - This is the annual perspectives paper on discontinued drugs in the field of
      pulmonary disease and allergy. It is part of a series of papers discussing drugs
      dropped from clinical development in the previous year and presented according to
      therapeutic indication. Specifically, this paper presents the six pulmonary and
      five allergy drugs discontinued in 2008. Information for this perspective was
      derived from a search of the Pharmaprojects database for drugs discontinued after
      reaching Phase I - III clinical trials.

PMID- 19852568
TI  - Seven years' experience in laparoscopic dissection of intact ovarian dermoid
      cysts.
AB  - A large case series on laparoscopic removal of dermoid cysts with a diameter
      between 3 and 12 cm, via an endobag, is reported (127 cysts in 121 premenopausal
      women). The incidence of spillage and recurrence rate of laparoscopic ovarian
      dermoid cystectomy, the duration of the surgical procedure, the length of
      hospitalization, the incidence of recurrence and pregnancies was evaluated. In
      2.5% of cases, the endobag ruptured during removal, and a total spillage rate of
      12% was seen. No signs or symptoms of peritonitis were observed regardless of
      cystic spillage or not. Laparoscopic cystectomy of dermoid cysts in premenopausal
      women is safe and effective and appears to be a valuable alternative to
      laparotomy. Controlled intraperitoneal spillage of cyst contents does not
      increase postoperative morbidity as long as an endobag is used and the peritoneal
      cavity is washed out thoroughly.

PMID- 19852569
TI  - Lateral episiotomy protects primiparous but not multiparous women from obstetric
      anal sphincter rupture.
AB  - OBJECTIVE: To identify the risk factors for obstetric anal sphincter rupture
      (OASR). DESIGN AND SETTING: Retrospective population-based register study.
      POPULATION: A total of 514,741 women with singleton pregnancy and vaginal
      delivery between 1997 and 2007 in Finland. METHODS: Primiparous (n = 2,315) and
      multiparous women (n = 534) with OASR were compared with primiparous and
      multiparous women without OASR by using stepwise logistic regression analysis.
      MAIN OUTCOME MEASURE: The OASR risk. RESULTS: Episiotomy decreased the likelihood
      of OASR for the primiparous [odds ratio (OR) 0.83, 95% CI (confidence interval)
      0.75-0.92], but not the multiparous women (OR 2.01, 95% CI 1.67-2.44). The
      strongest risk factors for OASR among the primiparous women were forceps delivery
      (OR 10.20, 95% CI 3.60-28.90), birth weight over 4,000 g (OR 4.66, 95% CI 3.86
      5.63), vacuum assisted delivery (OR 3.88, 95% CI 3.25-4.63), occiput posterior
      presentation (OR 3.17, 95% CI 1.64-6.15), and prolonged active second stage of
      birth (OR 2.06, 95% CI 1.65-2.58). Episiotomy was associated with decreased risks
      for OASR in vacuum assisted deliveries (OR 0.70, 95% CI 0.57-0.85). Risk factors
      for OASR among the multiparous women included forceps delivery (OR 10.13, 95% CI
      2.46-41.81), prolonged active second stage of the birth (OR 7.18, 95% CI 4.32
      11.91), birth weight over 4,000 g (OR 5.84, 95% CI 3.40-10.02), and vacuum
      assisted delivery (OR 4.17, 95% CI 3.17-5.48). CONCLUSIONS: The results support
      the restrictive use of episiotomy, since 909 episiotomies appear to be needed to
      prevent one OASR among primiparous women. Equivalent estimate in vacuum assisted
      deliveries among primiparous women was 66, favoring routine use of episiotomy in
      such cases.

PMID- 19852570
TI  - Laparoscopic treatment of diaphragmatic endometriosis causing chronic shoulder
      and arm pain.

PMID- 19852571
TI  - Microcephaly with chorioretinal dysplasia: two case reports and a review of the
      literature.
AB  - We describe two cases of chorioretinal dysplasia and microcephaly and review the
      current literature regarding this topic.

PMID- 19852572
TI  - Lack of association between the C2 allele of transferrin and age-related macular
      degeneration in the Israeli population.
AB  - BACKGROUND: Altered iron metabolism and transferrin expression were associated
      with neurodegenerations including age-related macular degeneration (AMD) and
      Alzheimer's disease (AD). Carriers of transferrin C2 allele alone or in
      combination with the hemochromatosis C282Y variant may have increased risk for
      developing AD. We aim to assess if these alleles also predispose to AMD. METHODS:
      DNA was collected from 290 AMD patients and 157 unaffected, age-matched,
      controls. Genotyping was performed for transferrin C1/C2 alleles and
      hemochromatosis C282Y allele, and association with AMD was evaluated. RESULTS:
      There was no association between the C1/C2 transferrin alleles and AMD.
      Hemochromatosis C282Y variant was identified in four individuals; one was an AMD
      patient and three were unaffected. CONCLUSION: Transferrin C2 and hemochromatosis
      C282Y alleles are not associated with increased risk for developing AMD in
      Israel.

PMID- 19852573
TI  - Subclinical optic neuropathy in Fabry disease.
AB  - BACKGROUND: Fabry disease is a rare X-linked lysosomal storage disorder, caused
      by the deficiency of alpha-galactosidase A. Ophthalmic features comprise a cornea
      verticillata, conjunctival aneurysms, tortuous conjunctival and/or retinal
      vessels, and anterior and posterior subcapsular cataracts. The issue of a
      possible subclinical optic neuropathy in Fabry disease has been raised recently.
      In this pilot study, we looked for signs of optic neuropathy in our cohort of
      Fabry patients. METHODS: Thirty-one Fabry patients (15 male, 16 female, mean age
      34 years) underwent an ophthalmological investigation consisting of assessment of
      best corrected visual acuity, slit lamp investigation, testing of pupillary
      reaction, funduscopy, applanation tonometry, and automated perimetry (Humphrey 30
      2). Twenty-nine patients received enzyme replacement therapy with agalsidase
      alpha (Replagal). RESULTS: Twenty-five of thirty-one patients showed the typical
      cornea verticillata, tortuous vessels were seen in 17. Two patients exhibited the
      pathognomonic posterior subcapsular spoke-like ('Fabry') cataract. Intraocular
      pressure (IOP) was < or = 20 mm Hg in all patients (mean IOP, range 10-20 mm Hg),
      and all had normal appearing discs on direct funduscopy. Ten out of 31 patients
      revealed pathological visual fields exhibiting relative central scotomas in
      automated 30 degrees static perimetry. CONCLUSIONS: In the absence of any other
      plausible explanation responsible for the field defects detected, we found
      subclinical optic neuropathy in 10/31 patients suffering from Fabry disease. This
      figure is in line with a previous report and raises the question whether
      perimetry should become a part of the ophthalmological examination in Fabry
      patients. Remarkably, our patients did not complain about any visual impairment.
      Further investigations are needed to more precisely define this complication of
      Fabry disease.

PMID- 19852575
TI  - Retinal vasculopathy in a family with autosomal dominant dyskeratosis congenita.
AB  - BACKGROUND: Dyskeratosis congenita is a rare multisystem bone marrow failure
      genetic disorder characterized by reticular skin hyperpigmentation, nail
      dystrophy, and oral leukoplakia. Clinical ophthalmic features in these patients
      include retinal hemorrhages, retinal vasculopathy, telangiectasia, and macular
      exudates. METHODS: Complete family medical history, clinical examination,
      complete blood profile, ophthalmologic examination, fundus color photography and
      fundus fluorescein angiography, and optical coherence tomography. RESULTS: We
      report a case of a young white adult male with a family history of clinically
      diagnosed autosomal dominant dyskeratosis congenita, who presented with retinal
      edema and peripheral retinal ischemia. The sister had milder manifestations and
      the father had very subtle manifestations. CONCLUSIONS: This case is consistent
      with the previously reported observations of genetic anticipation and variable
      expressivity in the retinal findings of dyskeratosis congenita.

PMID- 19852576
TI  - Characterization of CTNS mutations in Arab patients with cystinosis.
AB  - BACKGROUND: Cystinosis is an autosomal recessive disease characterized by
      impaired transport of free cystine out of lysosomes with resulting renal and
      ophthalmic manifestations. Mutations in CTNS, encoding cystinosin, are the only
      known cause of this autosomal recessive disorder with more than 85 different
      mutations described so far. PURPOSE: To identify CTNS mutations in Arab
      cystinosis patients. METHODS: In this study, we have analyzed the mutational
      spectrum of CTNS in a population of 21 patients from 13 families of Arab origin.
      The entire coding region and flanking intronic regions of CTNS were analyzed by
      direct sequencing. RESULTS: Eight mutations were identified, four of which are
      novel (c.530A>G, c.681G>A, 1013T>G, and c.1018_1041del). CONCLUSION: These
      alleles will provide the basis for routine molecular diagnosis of cystinosis in
      the region.

PMID- 19852574
TI  - Retinal pathology of a patient with Goldmann-Favre syndrome.
AB  - PURPOSE: To define the retinal pathology in an 88-year-old male affected with
      Goldmann-Favre syndrome with a 2 bp 5' A>C splice site mutation in the NR2E3
      gene. METHODS: Retinal tissue from the macula and periphery was processed for
      immunohistochemistry. Perimacular retina was processed for transmission electron
      microscopy. Cryosections were studied by indirect immunofluorescence, using well
      characterized antibodies to rhodopsin, cone cytoplasm, and cone opsins. The
      affected donor eye was compared to a postmortem matched normal eye. RESULTS: The
      retina was highly disorganized without laminar organization. The RPE was
      discontinuous in some perimacular regions. Large (>1 mm) spherical electrondense
      melanosomes were observed in the RPE and choroid by TEM. Rods were virtually
      absent in the affected retina. Cones were present in the macula, but were mostly
      absent from the retinal periphery. In addition, cone rosettes were observed in
      the perimacular area. Both red/green and blue cone opsins were distributed along
      the entire cellular expanse of the cone photoreceptors in the affected eye, but
      were restricted to the cone outer segments in the control retina. CONCLUSIONS:
      The histological data obtained from the retina of an elderly male patient with
      Goldmann-Favre syndrome showed an absence of rods and abnormal distribution of
      red/green and blue cone opsins.

PMID- 19852577
TI  - Autofluorescence and infrared retinal imaging in patients and obligate carriers
      with neuronal ceroid lipofuscinosis.
AB  - PURPOSE: To measure fundus autofluorescence (FAF) in patients and obligate
      carriers with Neuronal Ceroid Lipofuscinosis (NCL) and document fundus
      abnormalities in NCL patients using standard retinal photography and confocal
      infra-red (IR) imaging. METHODS: Twenty-seven patients with NCL, 50 obligate
      carriers of NCL, and 19 controls were imaged in IR and FAF modes by a confocal
      scanning laser opthalmoscope (HRA II, Heidelberg-Engineering, Inc). FAF
      intensities were referenced to the mean and standard deviation at the optic disk
      to remove inter-subject variance and then quantified along the horizontal and
      vertical meridians. RESULTS: For NCL subjects, FAF images were successfully
      obtained in 16 eyes (9 of 27 subjects). Of these, 11 eyes had severely reduced or
      extinguished FAF and 5 eyes (3 subjects) could be analyzed along the meridians.
      An NCL subject with bilateral bull's eye maculopathy showed overall increased
      FAF, the remaining 3 eyes had advanced retinal degeneration and showed reduced
      FAF. Four patterns of macular disease were observed: 1) bull's eye atrophy 2)
      retinal pigment epithelium (RPE) dropout without pigmentary alterations, 3) RPE
      dropout with pigmentary alterations, 4) RPE dropout with pigmentary alterations
      and retinal flecks. Standard photography revealed focal retinal flecks in
      addition to severe retinal atrophy, RPE dropout, pigmentary clumping, and
      constricted vessels. Linear striations near the optic disc were highlighted by IR
      imaging. Topographical comparison of images demonstrated the focal flecks were
      not hyperfluorescent while the linear striations showed slight increases in FAF.
      For obligate carriers, FAF profiles were similar to controls with a mild increase
      in mean FAF intensity. CONCLUSIONS: Patients with NCL show increases in retinal
      fluorophores in early stages and decreases in FAF in late stages of the disease.
      Obligate carriers of NCL have mildly elevated FAF but this finding is not a
      specific measure of the carrier state.

PMID- 19852578
TI  - Diagnosis of retinoblastoma: how good are referring physicians?
AB  - PURPOSE: To evaluate accuracy of the referring diagnoses of retinoblastoma to a
      tertiary cancer referral center. METHODS: Retrospective chart review of 352
      retinoblastoma-related patients seen by the ophthalmic oncology service during a
      4-year period from January 1, 2004 to October 21, 2008. Of these, 111 were
      referred with a suspicion of new retinoblastoma and were included in the study.
      Fundus photographs, gender, family history of retinoblastoma, initial symptoms,
      age, initial and referring physicians' specialty (eg, pediatrician, general
      ophthalmologist, retinal specialist) and their suspected diagnoses were recorded.
      The main outcome measure was accuracy of diagnosis given by referring providers.
      RESULTS: Of 111 patients, 62% had retinoblastoma and 38% did not. Persistent
      fetal vasculature (PFV) and Coats' Disease were the most common simulating
      lesions accounting for 31% and 29% of the simulating lesions respectively. Other
      simulating lesions included infrequent cases of rare conditions such as primary
      ocular teratoma, a retinal pigment epithelial tumor, and astrocytic hamartoma.
      CONCLUSIONS: Retinoblastoma continues to present a diagnostic dilemma. There has
      been limited improvement in the rate of correct diagnosis in the United States in
      the last 15 years. There has however been a change in the composition of
      misdiagnosed lesions with rare conditions accounting for more than 1/3 of cases.
      Attention to age, family history, laterality and presenting signs such as globe
      size can aid diagnosis of retinoblastoma.

PMID- 19852579
TI  - Mutations in KIF21A and PHOX2A are absent in 16 patients with congenital vertical
      incomitant strabismus.

PMID- 19852581
TI  - Early events of secondary degeneration after partial optic nerve transection: an
      immunohistochemical study.
AB  - Secondary degeneration in the central nervous system involves indirect damage to
      neurons and glia away from the initial injury. Partial transection of the dorsal
      optic nerve (ON) results in precise spatial separation of the primary trauma from
      delayed degenerative events in ventrally placed axons and parent somata. Here we
      conduct an immunohistochemical survey of secondary cellular changes in and around
      axons and their parent retinal ganglion cell (RGC) somata during the first 3 days
      after a restricted, dorsal ON transection. This is before the secondary loss of
      RGCs and axons projecting through the uninjured, ventral portion of the ON.
      Within 5 min, manganese superoxide dismutase (MnSOD; a marker of oxidative
      stress) co-localizes within the astrocytic network across the entire profile of
      the ON. Secondary astrocyte hypertrophy of immunofluorescent labeling was evident
      from 3 h, with sustained increases in myelin basic protein immunoreactivity
      across the nerve by 24 h. Increases in NG-2-positive oligodendrocyte precursor
      cells, ED-1-positive activated microglia/macrophages, and Iba1-positive reactive
      resident microglia/macrophage numbers were only seen in ON vulnerable to
      secondary degeneration by 3 days. Changes within RGC somata exclusively
      vulnerable to secondary degeneration were detected at 24 h, as evidenced by
      increases in MnSOD immunoreactivity, followed by increases in c-jun
      immunoreactivity at 3 days. Treatment with the voltage-gated calcium channel
      blocker lomerizine did not alter any measured outcome. We conclude that oxidative
      stress spreading via the astrocytic network and from injured axons to parent RGC
      somata is an early event during secondary degeneration, and containment is likely
      to be required in order to prevent further damage to the nerve.

PMID- 19852583
TI  - Low-level blast raises intracranial pressure and impairs cognitive function in
      rats: prophylaxis with processed cereal feed.
AB  - There is increasing evidence that even low levels of blast cause brain injury,
      but little is known about their thresholds and mechanisms. Exposure of rats to 10
      60 kPa blasts elevate intracranial pressure (ICP) in a dose-dependent manner and
      impair cognitive function. We have evaluated a prophylactic measure against these
      brain injuries in a rat animal model, consisting of feeding them processed
      cereal. This type of feed is known to ameliorate disturbances in secretion of
      body fluids and to have anti-inflammatory effects. In humans, intake of processed
      cereals is effective against intestinal diarrhea and also reduces the symptoms of
      Meniere's disease. Rats were given either standard laboratory feed or processed
      cereal feed for 2 weeks before exposure to blast in a shock tube. The ICP was
      monitored at different time points up to 1 week after exposure to a 60-kPa blast,
      and for up to 24 h after exposure to a 30-kPa blast. Maximal ICP elevation was
      reached at 10 h in both groups. In the group of rats on standard feed exposed to
      60 kPa, an ICP increase of 145% was noted at 10 h, and the corresponding increase
      in the rats fed processed cereal feed was only 50%. In rats exposed to a 30-kPa
      blast, those fed standard feed and processed cereal feed demonstrated increases
      of ICP of 80% and 40%, respectively. Cognitive function as measured by the Morris
      water maze was assessed in other groups of rats at 2 days after exposure to 10-
      or 30-kPa blasts. Their performance was significantly impaired at both exposure
      levels in rats on standard feed, but no functional impairment was seen in rats
      fed processed cereal feed.

PMID- 19852584
TI  - The status of the fourth ventricle and ambient cisterns predict outcome in
      moderate and severe traumatic brain injury.
AB  - Computed tomography (CT) of the head has become the diagnostic tool of choice,
      particularly for moderate and severe traumatic brain injury (TBI). Various CT
      characteristics are associated with outcome, and may therefore be used as outcome
      predictors. One of the most prominent predictors appears to be the status of the
      basal cisterns. This study describes the prognostic value of the appearance of
      individual cisterns and ventricles in relation to that of the basal cisterns.
      Further, we determine the interrater and intrarater reliability in the evaluation
      of the cisterns and ventricles. All consecutive moderate and severe adult TBI
      patients admitted to our hospital were included in this study as part of the
      prospective Radboud University Brain Injury Cohort Study (RUBICS). Outcome was
      assessed at 6 months post-trauma using the Glasgow Outcome Scale-Extended (GOS
      E). The predictive value of cisterns and ventricles was determined using
      multivariate binary logistic regression analysis. We included 126 moderate and
      574 severe TBI patients. Absence (complete obliteration), but also compression of
      the ambient cisterns and/or the fourth ventricle were strongly related to
      unfavorable outcome and death and emerged as the only significant outcome
      predictors after multivariate analysis. The assessment of the ambient cisterns
      and the fourth ventricle had a satisfactory inter- and intrarater reliability
      (kappa coefficients: 0.80-0.95). We conclude that, because obliteration of the
      ambient cisterns and the fourth ventricle both are better than the status of the
      basal cisterns as outcome predictors, they might be used in CT prediction models
      in cases of moderate and severe TBI.

PMID- 19852585
TI  - Systematic fluctuation expansion for neural network activity equations.
AB  - Population rate or activity equations are the foundation of a common approach to
      modeling for neural networks. These equations provide mean field dynamics for the
      firing rate or activity of neurons within a network given some connectivity. The
      shortcoming of these equations is that they take into account only the average
      firing rate, while leaving out higher-order statistics like correlations between
      firing. A stochastic theory of neural networks that includes statistics at all
      orders was recently formulated. We describe how this theory yields a systematic
      extension to population rate equations by introducing equations for correlations
      and appropriate coupling terms. Each level of the approximation yields closed
      equations; they depend only on the mean and specific correlations of interest,
      without an ad hoc criterion for doing so. We show in an example of an all-to-all
      connected network how our system of generalized activity equations captures
      phenomena missed by the mean field rate equations alone.

PMID- 19852586
TI  - What shapes pulse amplitude of intracranial pressure?
AB  - The pulsatile component of intracranial pressure (ICP) has been shown to be a
      predictor of outcome in normal pressure hydrocephalus (NPH) and traumatic brain
      injury (TBI). Experimental studies have demonstrated that the pulse amplitude of
      ICP (AMP(ICP)) is dependent on the mean ICP (mICP), and on the pulse amplitude of
      the cerebral arterial blood volume (AMP(CaBV)), according to the exponential
      craniospinal compliance curve. In this study, we compared the influence of mICP
      and AMP(CaBV) on AMP(ICP) in patients with NPH (infusion study) and TBI
      (spontaneous recording). We retrospectively analyzed 25 NPH and 43 TBI patients
      with continuous monitoring of ICP and cerebral blood flow velocity (CBFV), as
      assessed with transcranial doppler. AMP(CaBV) was extracted from the CBFV
      waveform. The influence of mICP and AMP(CaBV) on AMP(ICP) were determined using
      partial coefficients a, b, and c of the multiple regression model: AMP(ICP) = a *
      mICP + b * AMP(CaBV) + c. AMP(ICP) was more dependent on mICP in NPH patients
      than in TBI patients (partial coefficient a = 0.93 versus -0.03; p < 0.001). On
      the contrary, AMP(ICP) was more dependent on AMP(CaBV) in patients with TBI than
      in those with NPH (b = 0.86 versus 0.10; p < 0.001). This study shows that
      AMP(ICP) depends mostly on changes in mean ICP during cerebrospinal fluid (CSF)
      infusion studies in patients with NPH, and on changes in cerebral arterial blood
      volume (AMP(CaBV)) in TBI patients. Further clinical studies will reveal whether
      AMP(ICP) is a better indicator of clinical severity and outcome than mICP in TBI
      and NPH patients.

PMID- 19852587
TI  - A relationship between p27(kip1) and Skp2 after adult brain injury: implications
      for glial proliferation.
AB  - S-phase-associated kinase protein-2 (Skp2) is involved in ubiquitination and
      proteasome-mediated degradation of p27(kip1), which plays an important role in
      mammalian cell-cycle regulation and neurogenesis in the developing central
      nervous system. To investigate their expression and function in central nervous
      system injury and repair, we used a brain-penetrating injury model in adult rats.
      Western blot analysis showed a significant downregulation of p27(kip1) and a
      concomitant upregulation of Skp2 following brain injury, and their expression
      profiles were temporally correlative (r = -0.910, p = 0.037). Immunofluorescence
      double-labeling revealed that p27(kip1) was highly expressed in neurons (51%),
      astrocytes (72%), and microglia (76%) in the sham group, while its expression was
      decreased prominently in microglia (26%) and astrocytes (32%) at 3 days after
      injury. Meanwhile, Skp2 expression was very low in all cell types in the sham
      group; however, 3 days after injury, its expression was increased significantly
      in microglia (51%) and astrocytes (31%) (p < 0.001), and less significantly in
      neurons (8%) (p = 0.038), and the astrocytes and microglia had proliferated. We
      also examined the expression profiles of CDK2, threonine-187 phosphorylated
      p27(kip1), proliferating cell nuclear antigen (PCNA), and Ki67, and their changes
      correlated with the expression profiles of p27(kip1) and Skp2. Moreover, co
      immunoprecipitation data suggested that the protein-protein interactions between
      p27(kip1) and Skp2 were enhanced after injury. Taken with results of previous
      reports, we hypothesize the Skp2 is related to the downregulation of p27(kip1)
      expression after brain injury, and such an event may be associated with glial
      proliferation, including that of astrocytes and microglia.

PMID- 19852588
TI  - Shear bond strength of repair composite resin to an acid-etched and a laser
      irradiated feldspathic ceramic surface.
AB  - OBJECTIVE: The purpose of this study was to evaluate the shear bond strength of a
      repair composite resin to a feldspathic ceramic surface that had been either
      etched with 9.5% hydrofluoric acid (HFA), irradiated by an Er:YAG or Nd:YAG
      laser, or etched with 9.5% HFA after being irradiated by each laser type.
      BACKGROUND DATA: New findings have shown that combined laser irradiation and acid
      etching of a ceramic surface can be used to roughen ceramic surfaces. METHODS:
      Seventy-eight feldspathic ceramic discs were assigned to six surface treatment
      groups (n = 13): C, no treatment; HFA, 9.5% HFA etching; ER, Er:YAG laser
      irradiation; ND, Nd:YAG laser irradiation; ER + HFA, Er:YAG laser irradiation
      followed by HFA etching; ND + HFA, Nd:YAG laser irradiation followed by HFA
      etching. The surface of one disc from each treatment group was examined under a
      scanning electron microscope. After the surface treatments and silanization, a
      repair composite resin was applied to each disc using a commercial ceramic repair
      kit. Shear bond strength testing was then done after storing the specimens in
      distilled water for 24 h at 37 degrees C and thermocycling. Each ruptured
      specimen was examined under a stereoscopic light microscope. RESULTS: The highest
      shear bond strength was found after HFA etching, and the lowest was found after
      Er:YAG laser irradiation. HFA etching also caused the most pronounced changes of
      all the surface treatments. When HFA was applied after either laser irradiation,
      the fissures and cracks were larger than those seen on the only laser-irradiated
      surfaces. CONCLUSIONS: HFA etching is the most effective surface treatment for
      increasing the shear bond strength between a repair composite resin and a
      feldspathic ceramic surface. The shear bond strength after laser irradiation can
      be increased by HFA etching, but the strength of the bond is still smaller than
      that after HFA etching alone.

PMID- 19852589
TI  - A biographical portrait of Edward Hartley Angle, the first specialist in
      orthodontics, part 1.
AB  - Much of what is known about Edward Hartley Angle, MD, DDS (1855-1930), the
      acknowledged "father" of modern orthodontics, has been derived from secondary
      sources, accounts written by his contemporaries and others. New historical
      research using primary sources, largely the recently published four-volume
      sourcebook of Angle's correspondence and business transactions from 1899 to 1910,
      gives a broad view of the personality, interests, and activities of this prime
      mover in the evolution of orthodontics. This three-part article highlights
      aspects of Edward H. Angle's life and persona, based on new findings culled from
      his letters and other personal documents. Part 3 presents a biographical
      chronology of Angle's remarkable life.

PMID- 19852590
TI  - A biographical portrait of Edward Hartley Angle, the first specialist in
      orthodontics, part 2.

PMID- 19852591
TI  - A biographical portrait of Edward Hartley Angle, the first specialist in
      orthodontics, part 3.

PMID- 19852593
TI  - Reliability of traditional cephalometric landmarks as seen in three-dimensional
      analysis in maxillary expansion treatments.
AB  - OBJECTIVE: To evaluate intra-examiner and inter-examiner reliability of 3D CBCT
      generated landmarks previously used in traditional 2D cephalometry. MATERIALS AND
      METHODS: Twenty-four CBCTs NewTom 3G (Aperio Services, Verona, Italy) were
      randomly selected from patients participating in a clinical trial involving
      maxillary expansion treatments. The principal investigator located the landmarks
      five times, and four other investigators located the same landmarks once. Intra
      examiner and inter-examiner reliability values were determined using intraclass
      correlation coefficients (ICCs). To assist in interpretation of the clinical
      significance of landmark identification differences, average mean differences for
      x, y, and z landmark coordinates were determined from the repeated assessments.
      Landmarks then were separated into groups with respect to the region they
      represented and then were compared via repeated measures ANOVA and multiple
      comparisons via Bonferroni corrected alpha. RESULTS: Intra-examiner and inter
      examiner reliability for x, y, and z coordinates for all landmarks were
      acceptable, all being greater than 0.80. Most of the mean measurement differences
      obtained from trials within the principal investigator in all three axes were
      less than 1.5 mm. Inter-examiner mean measurement differences generally were
      larger than the intra-examiner differences. CONCLUSIONS: Based on this, the best
      landmarks for use in verifying expansion treatment results are Ekm, buccal
      surface, and apexes of upper molars, upper premolars and upper canines, and
      buccal surfaces of lower molars and lower canines. Foramen Spinosum, ELSA,
      Auditory External Meatus, and Dorsum Foramen Magnum demonstrated adequate
      reliability for determining a standardized reference system.

PMID- 19852592
TI  - Automated cephalometry: system performance reliability using landmark-dependent
      criteria.
AB  - OBJECTIVE: The purpose of the present study was to evaluate reliability of a
      system that performs automatic recognition of anatomic landmarks and adjacent
      structures on lateral cephalograms using landmark-dependent criteria unique to
      each landmark. MATERIALS AND METHODS: To evaluate the reliability of the system,
      the system was used to examine 65 lateral cephalograms. The area of each system
      identified anatomic structure surrounding the landmark and the position of each
      system-identified landmark were compared with norms using confidence ellipses
      with alpha = .01, which were derived from the scattergrams of 100 estimates
      obtained according to the method reported by Baumrind and Frantz. When the system
      identified area overlapped with the norm area, anatomic structure recognition was
      considered successful. In addition, when the system-identified point was located
      within the norm area, landmark identification was considered successful. Based on
      these judgment criteria, success rates were calculated for all landmarks.
      RESULTS: The system successfully identified all specified anatomic structures in
      all the images and determined the positions of the landmarks with a mean success
      rate of 88% (range, 77%- 100%). CONCLUSION: With the incorporation of the
      rational assessment criteria provided by confidence ellipses, the proposed system
      was confirmed to be reliable.

PMID- 19852594
TI  - Long-term follow-up of craniofacial alterations in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate changes in the craniofacial skeleton in relation to the
      changes in condylar alterations that occur during long-term follow-up in patients
      with juvenile idiopathic arthritis. MATERIALS AND METHODS: Temporomandibular
      joint (TMJ) involvement is defined as a condylar alteration that is observed on
      the orthopantomogram. Lateral cephalograms were used to determine linear and
      angular measurements. RESULTS: Seventy of 97 patients from the initial study
      cohort were included, with a mean follow-up of 68 months. The overall prevalence
      of condylar alterations and posterior rotation of the mandible decreased;
      however, the prevalence of retrognathia remained the same. Patients showed
      improvement in the degree of retrognathia and posterior rotation (40% ANB, 51% OP
      SN, and 44% GO-GN-SN). Improvement in the degree of retrognathia was seen more
      often in patients with improved condylar alterations than in patients with
      persistent alterations and in those without alterations (50%, 33%, and 28%,
      respectively). The degree of posterior rotation improved almost equally in
      patients without TMJ involvement and in patients with improved condylar
      alterations (57% and 50% by OP-SN, and 67% and 38% GO-GN-SN, respectively) and
      did not improve in patients with stable persistent alterations. CONCLUSION: Both
      condylar and craniofacial alterations can improve in patients with juvenile
      idiopathic arthritis.

PMID- 19852595
TI  - Relationship between occlusal force and mandibular condyle morphology. Evaluated
      by limited cone-beam computed tomography.
AB  - OBJECTIVE: To clarify the relationship between occlusal force and mandibular
      condyle morphology using clinical data. MATERIALS AND METHODS: The subjects were
      40 female patients with malocclusion. The mandibular condyle morphology was
      assessed by using limited cone-beam CT imaging. The maximum occlusal force was
      calculated by using pressure-sensitive films. Maxillofacial morphologies were
      analyzed by using data from lateral cephalograms. RESULTS: Correlation analysis
      showed that the occlusal force was correlated with the lateral and posterior
      radii of the condyles, and with the mandibular plane angle to the Frankfort
      horizontal plane (FH). Moreover, condylar length was significantly correlated
      with the occlusal plane angle to the FH, the mandibular plane angle to the FH,
      the ramus inclination, and the posterior facial height (S-Go). Low-occlusal-force
      patients tended to have smaller mandibular condyles. This size-related difference
      was more remarkable on the lateral and posterior side. CONCLUSIONS: Occlusal
      force influences not only maxillofacial morphology but also mandibular condyle
      morphology.

PMID- 19852596
TI  - A photographic system for the three-dimensional study of facial morphology.
AB  - OBJECTIVES: To test whether digital photographs supported by three-dimensional
      (3D) software are suitable for measuring the facial soft tissues of healthy
      subjects as compared with data obtained by a certified 3D computerized
      electromagnetic digitizer. MATERIALS AND METHODS: Three-dimensional soft tissue
      facial landmarks were obtained from the faces of 15 healthy young adults, using a
      3D computerized electromagnetic digitizer and a new low-cost photogrammetry
      system. Twelve linear and 18 angular measurements were computed. Errors between
      methods and repeatability of the new method were calculated. RESULTS: Systematic
      errors between methods were found for only two distances and three angles (paired
      t-test, P < .05). The mean absolute differences between methods were always lower
      than 3 mm and 3 degrees. Repeated digitization of photographs showed that the
      method was repeatable (no systematic differences; random errors lower than 1.6 mm
      and 3 degrees). Repeated sets of photographs showed random errors of up to 5.3 mm
      and 5.6 degrees, without systematic biases. CONCLUSION: The 3D photogrammetry
      system can provide reliable facial measurements. The method is relatively fast
      and requires only inexpensive equipment. It is simple to use for private
      practice, research, or other practice.

PMID- 19852597
TI  - Orthodontic treatment of malocclusion improves impaired skillfulness of
      masticatory jaw movements.
AB  - OBJECTIVE: To investigate whether individuals with malocclusion show less
      skillfulness, as represented by kinematic parameters that characterize
      masticatory jaw movement, compared with those having normal occlusion and, if so,
      to examine whether more skilled movements are achieved after completion of
      orthodontic treatment. MATERIALS AND METHODS: Lower incisor point movement in
      space during gum chewing was recorded, and the kinematic traits of such movement
      were compared among four subject groups: a Control Group (36 females with good
      occlusion), a Malocclusion Group (24 females with dental malocclusions), an
      Extraction Group (31 females who had received orthodontic treatment with premolar
      extraction) and a Nonextraction Group (27 females who had been treated
      orthodontically without tooth extraction). Before treatment, all subjects in the
      three experimental groups exhibited dental malocclusions and skeletal class I jaw
      base relationship. RESULTS: Compared with the Malocclusion Group, the lower
      normalized jerk-cost, the shorter phase durations, the more symmetric property of
      the velocity profile, and the smaller variance of lateral jaw-closing
      trajectories near the tooth intercuspation position were determined in the
      Extraction Group and the Nonextraction Group as well as in the Control Group.
      CONCLUSIONS: As measured by kinematic parameters such as normalized jerk-costs,
      velocity profile, and variance of movement trajectories near the endpoint of
      movement, dental malocclusions were associated with significantly lower
      skillfulness of masticatory jaw motion, whereas good occlusion and
      orthodontically improved occlusion (either with or without premolar extraction)
      were both associated with more skillful motion.

PMID- 19852598
TI  - Stepwise advancement Herbst appliance versus mandibular sagittal split osteotomy.
      Treatment effects and long-term stability of adult Class II patients.
AB  - OBJECTIVE: To compare the treatment effects and long-term stability of the
      stepwise Herbst appliance and mandibular sagittal split osteotomy in skeletal
      Class II adult patients. MATERIALS AND METHODS: Subjects comprised 16 patients in
      the Herbst group and another 16 patients in the surgery (mandibular sagittal
      split osteotomy) group. Lateral head films were taken before treatment (T0),
      after removal of the Herbst appliance/surgery (T1), after the fixed appliance
      treatment (T2), and 3 years after treatment (T3). All films were analyzed by
      standard cephalometrics and SO-analysis (analysis of changes in sagittal
      occlusion). RESULTS: All Herbst and surgery patients were treated successfully to
      Class I occlusal relationships with normal overjet and overbite. Both groups
      showed a significant change in mandibular base advancement (SNB, SNPg, Pg/OLp),
      which resulted in a decrease in the ANB angle, the Wits appraisal, and facial
      convexity. However, the surgery group showed larger changes in the parameters
      mentioned above. In terms of long-term stability, both groups achieved stable
      results, and no significant difference occurred over time. CONCLUSION: Stepwise
      advancement Herbst appliance therapy can be used to treat borderline skeletal
      Class II adult patients with long-term stability.

PMID- 19852599
TI  - Effects of mandibular advancement plus prohibition of lower incisor movement on
      mandibular growth in rats.
AB  - INTRODUCTION: To test the hypothesis that mandibular advancement with the use of
      a fixed functional appliance combined with prohibition of labial movement of the
      lower incisors will have no effect on mandibular growth in growing rats.
      MATERIALS AND METHODS: Fifteen 4-week-old male rats were divided into fixed,
      unfixed, and control groups (n = 5, each). Bite-jumping appliances were used in
      the fixed and unfixed groups. Sites of bone perforation and the lower incisors
      were connected with ligature wires in the fixed group. The ramus height,
      mandibular length, and inclination of lower incisors were examined for 4 weeks,
      and those values were compared among five intervals and three groups by through
      one-way analysis of variance models and the Bonferroni multiple comparison test
      for post hoc comparison. RESULTS: Increases in ramus height and mandibular length
      during the experimental period were 1.5 mm and 2.5 mm in the fixed group, 1 mm
      and 1.5 mm in the unfixed group, and 1.2 mm and 1.9 mm in the control group,
      respectively. Growth of ramus height and growth of mandibular length in the fixed
      group were greater than in the unfixed and control groups during the experimental
      period. The inclination of lower incisors in the unfixed group was increased 8.0
      degrees throughout the experimental period, which differed from results obtained
      in the other groups. CONCLUSIONS: Mandibular growth was accelerated effectively
      before and during the pubertal period in rats by mandibular advancement with a
      fixed functional appliance combined with prohibition of labial movement of the
      lower incisor.

PMID- 19852600
TI  - Optimal loading conditions for controlled movement of anterior teeth in sliding
      mechanics.
AB  - OBJECTIVE: To determine optimal loading conditions such as height of retraction
      force on the power arm and its position on the archwire in sliding mechanics.
      MATERIALS AND METHODS: A 3D finite element method (FEM) was used to simulate en
      masse anterior teeth retraction in sliding mechanics. The degree of labiolingual
      tipping of the maxillary central incisor was calculated when the retraction force
      was applied to different heights of a power arm set mesial or distal to the
      canine. RESULTS: When the power arm was placed mesial to the canine, at the level
      of 0 mm (bracket slot level), uncontrolled lingual crown tipping of the incisor
      was observed and the anterior segment of the archwire was deformed downward. At a
      power arm height of 5.5 mm, bodily movement was produced and the archwire was
      less deformed. When the power arm height exceeded 5.5 mm, the anterior segment of
      the archwire was raised upward and lingual root tipping occurred. When the power
      arm was placed distal to the canine, lingual crown tipping was observed up to a
      level of 11.2 mm. CONCLUSIONS: Placement of the power arm of an archwire between
      the lateral incisor and canine enables orthodontists to maintain better control
      of the anterior teeth in sliding mechanics. Both the biomechanical principles
      associated with the tooth's center of resistance and the deformation of the
      archwire should be taken into consideration for predicting and planning
      orthodontic tooth movement.

PMID- 19852601
TI  - Molecular markers of early orthodontic tooth movement.
AB  - OBJECTIVE: To understand the molecular basis of early orthodontic tooth movement
      by looking at the expression of KI-67, runt-related transcription factor 2
      (Runx2), and tumor necrosis factor ligand superfamily member 11 (RANKL) proteins.
      MATERIALS AND METHODS: We employed a rat model of early orthodontic tooth
      movement using a split-mouth design (where contralateral side serves as a
      control) and performed immunohistochemical staining to map the spatial expression
      patterns of three proteins at 3 and 24 hours after appliance insertion. RESULTS:
      We observed increased expression of KI-67, a proliferation marker, and RANKL, a
      molecule associated with osteoclastic differentiation, in the compression sites
      of the periodontal ligament subjected to 3 hours of force. In contrast, there was
      increased expression of KI-67 and Runx2, a marker of osteoblast precursors, in
      tension areas after 24 hours of force. Decreased KI-67 expression in the mesial
      and distal regions of the periodontal ligament was observed at the midpoint of
      the tooth root. CONCLUSIONS: The early RANKL expression indicates that at this
      early stage cells are involved in osteoclast precursor signaling. Also, decreased
      KI-67 expression found near the midpoint of the tooth root is believed to
      represent the center of rotation, providing a molecular means of visualizing
      mechanical loading patterns.

PMID- 19852602
TI  - Effects of intrusive force on selected determinants of pulp vitality.
AB  - OBJECTIVE: To determine the activity of aspartate aminotransferase (AST) in the
      pulp of orthodontically intruded teeth and to test the sensitivity of these teeth
      by means of electrical pulp testing (EPT). MATERIALS AND METHODS: The study
      sample consisted of 21 healthy subjects who needed extraction of first premolars
      for orthodontic reasons. In every subject, one premolar included in a 0.016''-
      0.022'' stainless steel spring from the first molar and loaded by the force was
      regarded as a test tooth. The magnitude of the intrusive tipping force for every
      tooth was calculated with the use of ANSYS 10.0 software. The contralateral
      premolar was used as a control tooth. After 7 days, the spring was removed, and
      EPT was applied to test and control teeth. The teeth were extracted, and the
      dental pulp was removed. AST activity in the pulp was determined
      spectrophotometrically at 20 degrees C. RESULTS: Estimated mean AST activity
      values ranged from 0.572 +/- 0.097 U/mg in the test teeth to 0.348 +/- 0.053 U/mg
      in the control teeth (P < .01). The EPT test showed significant differences
      between test and control teeth (P < .001). The mean estimated magnitude of the
      intrusive tipping force was 61 +/- 4.5 g. CONCLUSION: Seven days of orthodontic
      intrusion can cause metabolic changes in the pulp expressed by increased AST
      activity. The increased threshold in the pulp reaction to EPT indicates changes
      in the neural response of the pulp.

PMID- 19852604
TI  - Changes of caspase-1 after the application of orthodontic forces in the
      periodontal tissues of rats.
AB  - OBJECTIVE: To investigate the changes of caspase-1 in orthodontic tooth movement
      and to determine whether the changes are phase-specific. MATERIALS AND METHODS:
      Eighty Wistar rats were included in this study. Sentalloy closed-coil springs
      were placed to induce a mesial traction force on the lower right first molar. The
      animals were killed after 1, 3, 7, and 14 days (n = 20 at each time point). The
      mandibles of 10 rats were sampled for histomorphometric analysis and
      immunohistochemical assay, and the periodontal tissues of 10 other rats were
      sampled for detecting caspase-1 mRNA and protein by real-time RT-PCR and by
      Western blotting, respectively. RESULTS: The inflammatory reaction was evident in
      paraffin sections with hematoxylin-eosin staining. The immunohistochemical assay
      showed that orthodontic forces significantly increased the number of caspase-1
      positive cells in the periodontal ligament (PDL). Mechanical force triggered an
      increase of caspase-1 mRNA in periodontal tissues. The expression of caspase-1
      mRNA increased from day 1, reached the peak on day 3, and then decreased. The
      results of Western blotting indicated that the levels of both procaspase-1 and
      P20 subunit significantly increased after the application of orthodontic forces,
      compared with those in controls (P < .05). CONCLUSION: Caspase-1 level increases
      during orthodontic tooth movement and changes with different phases, which might
      play a significant role in orthodontic tooth movement.

PMID- 19852603
TI  - MMP-2, MMP-9, and iNOS expression in human dental pulp subjected to orthodontic
      traction.
AB  - OBJECTIVE: To test the hypothesis that some metalloproteinases (MMP-2, MMP-9) and
      inducible nitric oxide synthetase (iNOS) enzymes in dental pulp samples do not
      vary when subjected to orthodontic treatment. MATERIALS AND METHODS: Human dental
      pulps were taken from male and female patients (N=10; age 10-14 years). A
      straight wire technique was used with nickel-titanium or steel archwires. The
      increase of pressure applied on teeth was gradual. Five patients were subjected
      to premolar extractions after 14 months of treatment and one after 24 months.
      Samples were Bouin-fixed, paraffin-embedded, and afterwards processed for
      immunohistochemistry using anti-MMP-2, anti-MMP-9, and anti-iNOS antibodies.
      RESULTS: A reduction of MMP-2, MMP-9, and iNOS expression occurred in treated
      samples. This became more evident with increased treatment time. CONCLUSION: The
      hypothesis is rejected. The reduction of expression of those proteins revealed a
      time-dependent relationship.

PMID- 19852605
TI  - Cytotoxicity and degree of conversion of orthodontic adhesives.
AB  - OBJECTIVES: To test the hypothesis that there is no difference in the
      cytotoxicity related to the modes of polymerization of five commercially
      available orthodontic bonding resins, with and without an oxygen-inhibited layer
      (OIL), and to evaluate the degree of conversion (DC) of these resins and
      correlate this to cytotoxicity. MATERIALS AND METHODS: Five commercially
      available orthodontic bonding resins were tested for cytotoxicity and DC. Thirty
      six disks of standardized dimensions, for each resin, were used for cytotoxicity
      assessment. Half of them were washed with 99% acetone to remove the OIL (washed
      resins), and the remaining disks were left intact (intact resins). Glass disks
      were used as a control. Vero cells were exposed to intact and washed resins on
      day 1. Cell viability was determined by tetrazolium bromide reduction assay 1, 3,
      and 6 days after exposure. The DC of the adhesive specimens of each resin,
      prepared with a procedure identical to the clinical bonding process, was assessed
      by Fourier transform infrared spectroscopy. RESULTS: Single-cured systems were
      comparatively less cytotoxic than dual-cured systems. With removal of the OIL,
      increased cell viability was noted only with two resins on all three days. Resins
      tested showed differences in DC. A positive correlation was demonstrated by two
      resins. CONCLUSION: The hypothesis is rejected. Single-cured systems are superior
      to dual-cured systems in exhibiting comparatively less toxicity and higher DC. A
      significant positive correlation was not established between cytotoxicity and DC.

PMID- 19852606
TI  - Opinions of American and Swedish orthodontists about the role of erupting third
      molars as a cause of dental crowding.
AB  - OBJECTIVE: To compare the opinions of Swedish orthodontists and American
      orthodontists regarding the association between third molar eruption and dental
      crowding. MATERIALS AND METHODS: A survey was distributed to Swedish
      orthodontists (n = 230) asking their views on the force exerted by erupting third
      molars, its relationship to crowding, and their recommendations for prophylactic
      removal. Results were compared with those from a similar study conducted in the
      United States. Chi square analysis was used to determine differences in responses
      to questions between Swedish and American orthodontists. P < or = .05 was
      considered significant. RESULTS: Both Swedish and American orthodontists believed
      that lower third molars were more likely than upper third molars to cause force
      (65% and 58% for Swedish and American orthodontists, respectively) and crowding
      (42% and 40%, respectively). No statistically significant differences were seen
      between the answers of American and Swedish orthodontists regarding the role of
      upper and lower third molars in causing crowding. Although only 18% of Swedish
      orthodontists "generally" or "sometimes" recommended prophylactic removal of
      mandibular third molars, 36% of American orthodontists "generally" or "sometimes"
      recommended removal (P < .0001). CONCLUSIONS: Most orthodontists in the United
      States and Sweden do believe that erupting lower third molars exert an anterior
      force; however, they also believe that these teeth "rarely" or "never" cause
      crowding of the dentition. The reason that more American orthodontists recommend
      prophylactic removal of mandibular third molars remains unexplained.

PMID- 19852607
TI  - Influence of first premolar extraction on mandibular third molar angulation.
AB  - OBJECTIVE: To compare the angular changes in the developing mandibular third
      molars in both first premolar extraction and nonextraction cases and to determine
      whether premolar extraction results in a more mesial movement of the mandibular
      buccal segment and causes favorable rotational changes in the mandibular third
      molar tilt, which can enhance later eruption of the third molars. MATERIALS AND
      METHODS: Pretreatment (T1) and posttreatment (T2) panoramic radiographs were
      taken of 25 subjects who had been treated by the extraction of all the first
      premolars and 25 subjects who had been treated with nonextraction. The horizontal
      reference plane was used to measure and compare the changes in the angles of the
      developing mandibular third molars. RESULTS: The mean uprighting of the
      mandibular third molars seen in the extraction group was 8.2 +/- 5.4 degrees on
      the left side and 6.3 +/- 6.5 degrees on the right side following treatment (T2 -
      T1). For the nonextraction group the mean difference was 1.3 +/- 4.3 degrees on
      the left side and 1.7 +/- 5.4 degrees on the right side. There was a
      statistically significant difference between the groups (P = .012 on the right
      side and P < .001 on the left side). CONCLUSIONS: Premolar extractions had a
      positive influence on the developing third molar angulations. Nonextraction
      therapy did not have any adverse effects.

PMID- 19852608
TI  - Microbiologic changes in subgingival plaque after removal of fixed orthodontic
      appliances.
AB  - OBJECTIVE: To evaluate changes that occur in the subgingival microbiota after
      removal of fixed orthodontic appliances using polymerase chain reaction (PCR).
      MATERIALS AND METHODS: Thirty orthodontic patients (11 males and 19 females; aged
      20 +/- 7.3 yr) were included in this study. Subgingival plaque samplings were
      gathered from the disto-buccal gingival crevice of the left upper central
      incisors and the left lower central incisors, and from the mesio-buccal gingival
      crevice of the left upper first molars and the left lower first molars, at two
      different times: 2 weeks before appliance removal (T1), and 3 months after
      appliance removal (T2). DNA was extracted from the samples and the 16S rRNA-based
      PCR detection method was used to determine the prevalence of Actinobacillus
      actinomycetemcomitans , Tannerella forsythia , Campylobacter rectus , Eikenella
      corrodens , Porphyromonas gingivalis , Prevotella intermedia , Prevotella
      nigrescens , and Treponema denticola , which are considered as putative
      periodontopathogens. RESULTS: The frequency of positive sites at T1 and T2 was
      65% and 43.3% for C. rectus , and 53.3% and 30.8% for E. corrodens ,
      respectively. For the other bacteria, the frequency tended to be reduced between
      times. CONCLUSION: Periodontopathogens during orthodontic treatment were
      significantly reduced within 3 months of appliance removal. However, how long it
      takes to return to the preorthodontic composition of the subgingival microbiota
      and whether it happens at all remain to be seen.

PMID- 19852609
TI  - Pitch and longitudinal fluting effects on the primary stability of miniscrew
      implants.
AB  - OBJECTIVE: To test the hypotheses that pitch and fluting have no effect on the
      primary stability of miniscrew implants (MSIs). MATERIALS AND METHODS: Maximum
      placement torque and pullout strength of experimental MSIs were compared with
      those of control MSIs with the use of synthetic and cadaver bone. MSIs with 1.00
      mm pitch were compared with those with 1.25 mm and 0.75 mm pitch; MSIs with three
      longitudinal flutes were compared with the same MSIs without flutes. A total of
      60 MSIs (15 of each design) were evaluated with synthetic bone; a split-mouth
      cadaver model was used to compare the three experimental designs against the 1 mm
      control MSIs (total of 90 MSIs). RESULTS: The synthetic bone model showed higher
      placement torque and pullout strength for the 0.75 pitch than for the 1.0 mm and
      1.25 mm pitch MSIs, but differences were significant (P < .05) only for pullout
      strength. The cadaver model showed no significant differences in placement torque
      or pullout strength associated with pitch. Both synthetic and cadaver bone models
      showed that MSIs with flutes had significantly (P < .05) higher placement torque
      and pullout strength. Spearman correlations between placement torque and pullout
      strength were statistically significant for both synthetic (r = .504) and cadaver
      (r = .502) bone. CONCLUSION: Within limits, decreasing MSI pitch increases
      pullout strength, and fluting increases both placement torque and pullout
      strength.

PMID- 19852610
TI  - Cephalometric floating norms as a guide toward a harmonious individual
      craniofacial pattern among Filipinos.
AB  - OBJECTIVE: To construct a harmony box based on correlated cephalometric
      variables, which may serve as a valuable diagnostic tool in orthodontic treatment
      planning, by analyzing the harmonious relationships of existing individual
      craniofacial patterns among Filipinos. MATERIALS AND METHODS: Eighty-one
      subjects, 37 females and 44 males, were selected from the student population of a
      University according to established inclusion criteria. Five cephalometric
      angular measurements were obtained and digitized. Pearson correlation
      coefficients described the high association among the five variables. The
      bivariate linear regression analysis was used to construct a harmony box, which
      contained the cephalometric floating norms of the five correlated variables.
      Multiple regression analysis and the standard error of the estimate were
      calculated to construct the harmony schema, which describes the individual
      craniofacial pattern. RESULTS: Correlations between the five variables were
      significant at .001 and .05 levels. Linear regression equations with
      corresponding r(2) and standard error of the estimate (SE) were illustrated as
      the harmony box. The multiple correlation coefficient R, the adjusted R(2), and
      the SE when one of the five measured variables was predicted from the remaining
      four by means of a multiple regression analysis were displayed as the harmony
      schema. CONCLUSION: The cephalometric floating norms describing the individual
      craniofacial pattern among Filipinos were established based on five correlated
      variables in the form of a harmony box.

PMID- 19852611
TI  - Effect of celecoxib on emotional stress and pain-related behaviors evoked by
      experimental tooth movement in the rat.
AB  - OBJECTIVE: To test the efficacy of an animal model of pain and stress and
      evaluate the effects of celecoxib administered when orthodontic force is applied.
      MATERIALS AND METHODS: A 20-g reciprocal force was applied via an orthodontic
      appliance to the maxillary left first and second molars of 7-week-old male
      Sprague-Dawley rats. Rat behavior was evaluated at 5, 24, and 48 hours after the
      appliance was set. Behavior was assessed in a test field by the number of lines
      crossed in the first 30 seconds and 5 minutes following force application; number
      of lines crossed to the center; rearing time; and facial grooming time.
      Experimental group 1 received intraperitoneal administration of 30 mg/kg
      celecoxib before every behavioral test. Experimental group 2 received 90 mg/kg
      before the first behavioral test, and physiologic saline was administered before
      the remaining behavioral tests. Control groups received saline before every
      behavioral test and were given passive (passive control group) and active (active
      control group) appliances, respectively. RESULTS: Parameters related to pain
      increased in the active controls, whereas the parameters in the experimental
      groups decreased to the level seen in the passive controls. Statistically
      significant differences in pain-related behavior between control and experimental
      groups were found at 5 and 24 hours after placing the appliance. Stress-related
      behavior was significantly less in the experimental groups compared to the active
      control group during experimental periods. CONCLUSIONS: The administration of
      celecoxib relieves pain- and stress-related behavior evoked by orthodontic tooth
      movement in the rat. This model might be a useful tool for the evaluation of pain
      and stress.

PMID- 19852612
TI  - Pain and orthodontic treatment.
AB  - OBJECTIVE: To explore whether patients' pain experiences and orthodontists'
      assessments of their patients' pain levels are consistent and whether
      orthodontists are aware of their patients' use of pain medication. MATERIALS AND
      METHODS: Survey data were collected from 116 adolescent patients (44 male, 72
      female; aged 10 to 19 years; mean age, 14.27 years) and from their orthodontic
      care providers. RESULTS: While only 18.0% of these patients agreed that they had
      pain during their last orthodontic appointment, 58.5% indicated that they
      experienced pain for a few days after their appointment. On average, dentists
      underestimated the patients' pain during the last appointment (rated on a 5-point
      scale, with 1 indicating no pain: providers = 2.01 vs patients = 2.28; P = .042),
      immediately after the last appointment (1.93 vs 2.34; P = .005), and 1 day (1.77
      vs 2.53; P < .001) and 2 days (1.57 vs 2.19; P < .001) after the previous
      appointment. Only 26.5% of the patients used pain medication immediately
      following and 1 day after the last appointment. Providers underestimated the
      amount of medication used. CONCLUSION: Orthodontists underestimated the degree to
      which orthodontic treatment caused pain for their patients and their patients'
      use of pain medication.

PMID- 19852613
TI  - Blood flow distribution of repaired lip in cleft lip patients.
AB  - OBJECTIVE: To investigate the blood flow distribution in the repaired lip of
      cleft patients using a laser Doppler imager and to evaluate the difference in
      blood flow of the scar tissue between unilateral cleft lip patients with and
      without cleft palate. MATERIALS AND METHODS: Twenty patients with either
      unilateral cleft lip only (CL group, n = 8) or cleft lip and palate (CLP group, n
      = 12) were used as subjects. The blood flow of the upper lip was two
      dimensionally visualized by a color scale alongside the corresponding photo image
      of the tissue surface with laser Doppler imaging. The upper lip photo image was
      divided into five regions: scar, white lip on the cleft side, white lip on the
      noncleft side, red lip on the cleft side, and red lip on the noncleft side. The
      average flux score (AFS), which is proportional to blood flow, was analyzed in
      each region. RESULTS: The AFS for the scar region was significantly (P < .05)
      lower than in the other four regions. The AFS for the red lip on the cleft side
      was not significantly different from that for the noncleft side. The white lip
      revealed a significantly (P < .05) higher score on the cleft side than on the
      noncleft side. The AFS ratio (AFS in the scar region/AFS in the white lip region)
      was significantly (P < .01) lower in the CLP group than in the CL group.
      CONCLUSIONS: These results suggest that blood flow distribution in the repaired
      lip might be affected by the anatomic features of the cleft.

PMID- 19852614
TI  - Psychosocial impact of dental esthetics on quality of life in adolescents.
AB  - OBJECTIVE: To test the hypothesis that several dimensions of the self-perceived
      psychosocial impacts of dental esthetics are not associated with grades of
      malocclusion, oral health-related quality-of-life measures, and body self-image
      in adolescents. MATERIALS AND METHODS: This cross-sectional study included a
      convenience sample of 301 adolescents (mean age 16.1 +/- 1.8 years, 58.1% female
      subjects). Demographic data were collected and dental conditions were assessed.
      The Dental Aesthetic Index (DAI) was used for assessment of malocclusion and
      determination of orthodontic treatment needs. The short form of the Oral Health
      Impact Profile (OHIP-14), the Psychosocial Impact of Dental Aesthetics
      Questionnaire (PIDAQ), and the Body Satisfaction Scale (BSS) were used to measure
      adolescents' self-perceived variables. RESULTS: All variables (DAI, OHIP-14, and
      BSS) were correlated with PIDAQ (P < .001). Stepwise multiple regression analysis
      revealed significant associations (P < .001) of independent variables with the
      total score of PIDAQ (R(2) = 0.29) and dental self-confidence (R(2) = 0.30),
      social impact (R(2) = 0.14), psychological impact (R(2) = 0.23), and esthetic
      concern (R(2) = 0.13). CONCLUSION: The hypothesis is rejected. A broad range of
      adolescents' self-perceived impact of dental esthetics is influenced by severity
      of malocclusion, oral health-related quality of life, and body satisfaction.

PMID- 19852615
TI  - Face and neck dermatitis from a stainless steel orthodontic appliance.
AB  - Although nickel is the most common cause of contact allergy, nickel-containing
      orthodontic appliances seldom cause adverse reactions that result in
      discontinuation of treatment. We report on an eruption of dermatitis in the face
      and neck of an adult female patient after placement of a rapid maxillary
      expansion appliance (RME). Because the patient suspected nickel allergy, her
      tolerance to the appliance material was tested intraorally before treatment by
      cementing bands on four teeth for a week. No visible adverse reactions were seen
      during the test. One week after cementation of the RME appliance, the patient
      reported strong itching of the face and a red rash. Clinical examination showed
      itchy papular erythema on the face and neck. No intraoral reactions or symptoms
      were present. The RME appliance was removed, and symptoms disappeared in 4 to 5
      days. The patient was referred for a nickel patch test, which gave a strong
      positive result. Adverse patient reactions of potential allergic origin should be
      diagnosed carefully, and their possible impact on further treatment should be
      evaluated accordingly.

PMID- 19852616
TI  - Selection, epistasis, and parent-of-origin effects on deleterious mutations
      across environments in Drosophila melanogaster.
AB  - Understanding the nature of selection against deleterious alleles is central to
      determining how populations are affected by the constant influx of new mutations.
      Important progress has been made in estimating basic attributes of the
      distribution of selection coefficients and gene interaction effects (epistasis).
      Although most aspects of selection are likely to be context dependent, little is
      known about the effect of stress on selection and epistasis at the level of
      individual genes, especially in multicellular organisms. Using Drosophila
      melanogaster, we measure how selection on 20 mutant alleles is affected by direct
      and indirect genetic factors across two environments. We find that environmental
      stress increases selection against individual mutations but reduces selection
      against combinations of mutations (i.e., epistasis becomes more positive). In
      addition, we find a high incidence of indirect genetic effects whereby the
      strength of selection against the alleles carried by offspring is dependent on
      the genotypes of their parents.

PMID- 19852617
TI  - Selective isolation of young cells from human corneal endothelium by the sphere
      forming assay.
AB  - This study aimed to investigate whether a representative adult stem
      cell/precursor cell isolation method (the sphere-forming assay) could isolate
      cells with differences of telomere length, telomerase activity, and
      characteristics reflecting senescence. The sphere-forming assay was performed to
      obtain precursors from cultured sixth passage (P6) human corneal endothelial
      cells (CECs). P6 and P7 cultured CECs were used as the controls. Telomere length,
      telomerase activity, and senescence-associated factors were evaluated in
      precursors and controls. Precursors obtained from the spheres had longer
      telomeres and higher telomerase activity than cultured P6 cells. Strong positive
      staining for senescence-associated beta-galactosidase activity was detected in P6
      and P7 cultured CECs, whereas little or no staining was detected in the
      precursors within spheres obtained from P6-cultured CECs or their progeny. The
      progeny of spheres derived from cultured CECs were small regular cells that grew
      at a higher density and contained more 5-bromo-2'-deoxyuridine-incorporating
      cells compared with the parental cultured cells. These findings indicate that the
      sphere-forming assay enriches precursors with longer telomeres, higher telomerase
      activity, and younger progeny than the original cells. Thus, the sphere-forming
      assay may contribute to obtaining the young cells needed for regenerative
      medicine.

PMID- 19852618
TI  - Inverse-gene-for-gene infection genetics and coevolutionary dynamics.
AB  - The genetic basis of infection in host-parasite interactions has traditionally
      been considered within the framework of either gene-for-gene (GFG) or matching
      allele models. We present an alternative model, termed inverse-gene-for-gene
      (IGFG), where pathogen infectiousness is determined by parasite recognition of
      host signals and/or receptors or where there is active host searching by
      parasites. We show that coevolutionary dynamics under IGFG are both qualitatively
      and quantitatively different from those of the GFG model, and we suggest that
      this new approach may be applicable to a range of important host-parasite systems
      that are not currently catered for by the existing frameworks.

PMID- 19852619
TI  - On the use of dynamic Bayesian networks in reconstructing functional neuronal
      networks from spike train ensembles.
AB  - Coordination among cortical neurons is believed to be a key element in mediating
      many high-level cortical processes such as perception, attention, learning, and
      memory formation. Inferring the structure of the neural circuitry underlying this
      coordination is important to characterize the highly nonlinear, time-varying
      interactions between cortical neurons in the presence of complex stimuli. In this
      work, we investigate the applicability of dynamic Bayesian networks (DBNs) in
      inferring the effective connectivity between spiking cortical neurons from their
      observed spike trains. We demonstrate that DBNs can infer the underlying
      nonlinear and time-varying causal interactions between these neurons and can
      discriminate between mono- and polysynaptic links between them under certain
      constraints governing their putative connectivity. We analyzed conditionally
      Poisson spike train data mimicking spiking activity of cortical networks of small
      and moderately large size. The performance was assessed and compared to other
      methods under systematic variations of the network structure to mimic a wide
      range of responses typically observed in the cortex. Results demonstrate the
      utility of DBN in inferring the effective connectivity in cortical networks.

PMID- 19852620
TI  - A comparison of sodium calcium edetate (edetate calcium disodium) and succimer
      (DMSA) in the treatment of inorganic lead poisoning.
AB  - INTRODUCTION: This article reviews the experimental and clinical studies that
      have compared the efficacy (impact on urine lead excretion, blood and tissue lead
      concentrations, resolution of features and survival) of sodium calcium edetate
      (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead
      poisoning. It also summarizes the pharmacokinetic and pharmacodynamic aspects and
      the adverse effects of treatment. METHODS: Medline, Toxline, and Embase were
      searched for all available years to June 2009. PHARMACOKINETICS AND
      PHARMACODYNAMICS: The absorption of oral DMSA is more complete than sodium
      calcium edetate; the latter has to be administered parenterally. Both antidotes
      are distributed predominantly extracellularly. Sodium calcium edetate is not
      metabolized, whereas DMSA is extensively metabolized to mixed disulfides of
      cysteine. The two antidotes have elimination half-lives of less than 60 min.
      There is no evidence that either antidote crosses the blood-brain barrier to any
      major extent. Sodium calcium edetate chelates lead by displacement of the central
      Ca2+ ion with Pb2+. The nature of the DMSA-lead chelate is less clearly defined.
      There is evidence that the mixed disulfides of cysteine are the active chelating
      moiety in humans. If this is the case, this suggests that chelation occurs
      principally, if not exclusively, in the kidney. The primary source of lead
      mobilized by sodium calcium edetate is bone with an additional contribution from
      kidney and liver. EFFICACY: Comparison of the experimental studies is complicated
      by substantial variations in study design, particularly the antidote dose, the
      route and duration of treatment, the amount and duration of lead dosing, and lack
      of direct comparison between antidotes (comparison was usually made with
      control). In experimental studies that used equimolar and clinically relevant
      antidote doses and assessed the impact of DMSA and sodium calcium edetate on
      urine lead excretion and/or blood lead concentrations, similar results were
      found, though no direct comparison between antidotes was undertaken. DMSA was
      more effective than sodium calcium edetate in reducing the kidney lead
      concentration, sodium calcium edetate was more effective than DMSA in reducing
      bone lead concentrations, and there was no consistently observed effect of
      chelation therapy on brain lead concentrations in these experimental studies.
      Only two clinical studies have compared equimolar or similar antidote doses in
      enhancing urine lead excretion; there was no statistical difference between the
      antidotes, though both studies had limitations. DMSA and sodium calcium edetate
      had a comparable impact on lowering blood lead concentrations in a clinical study
      using similar molar antidote doses. ADVERSE EFFECTS: Sodium calcium edetate
      causes dose-related nephrotoxicity. Both agents deplete zinc and copper, the
      effect on zinc being significantly greater with sodium calcium edetate. A
      transient increase in hepatic transaminase activity has been reported with both
      antidotes but appears to be more common with DMSA and neither has been associated
      with clinically significant hepatic toxicity. Skin lesions during treatment with
      sodium calcium edetate are unusual and have been attributed to zinc deficiency.
      DMSA has occasionally been associated with a severe mucocutaneous reaction
      necessitating discontinuation of therapy. CONCLUSIONS: Oral DMSA and parenteral
      sodium calcium edetate are both effective chelators of lead. There are currently
      insufficient data, however, to conclude that either antidote is superior in
      enhancing lead excretion. Both antidotes resolve the symptoms of moderate and
      severe lead toxicity rapidly. Although there is greater clinical experience with
      sodium calcium edetate, particularly in the treatment of lead encephalopathy,
      oral DMSA may now be considered as an alternative in circumstances where oral
      therapy is preferable.

PMID- 19852621
TI  - Are calcium oxalate crystals involved in the mechanism of acute renal failure in
      ethylene glycol poisoning?
AB  - INTRODUCTION: Ethylene glycol (EG) poisoning often results in acute renal
      failure, particularly if treatment with fomepizole or ethanol is delayed because
      of late presentation or diagnosis. The mechanism has not been established but is
      thought to result from the production of a toxic metabolite. METHODS: A
      literature review utilizing PubMed identified papers dealing with renal toxicity
      and EG or oxalate. The list of papers was culled to those relevant to the
      mechanism and treatment of the renal toxicity associated with either compound.
      ROLE OF METABOLITES: Although the "aldehyde" metabolites of EG, glycolaldehyde,
      and glyoxalate, have been suggested as the metabolites responsible, recent
      studies have shown definitively that the accumulation of calcium oxalate
      monohydrate (COM) crystals in kidney tissue produces renal tubular necrosis that
      leads to kidney failure. In vivo studies in EG-dosed rats have correlated the
      severity of renal damage with the total accumulation of COM crystals in kidney
      tissue. Studies in cultured kidney cells, including human proximal tubule (HPT)
      cells, have demonstrated that only COM crystals, not the oxalate ion,
      glycolaldehyde, or glyoxylate, produce a necrotic cell death at toxicologically
      relevant concentrations. COM CRYSTAL ACCUMULATION: In EG poisoning, COM crystals
      accumulate to high concentrations in the kidney through a process involving
      adherence to tubular cell membranes, followed by internalization of the crystals.
      MECHANISM OF TOXICITY: COM crystals have been shown to alter membrane structure
      and function, to increase reactive oxygen species and to produce mitochondrial
      dysfunction. These processes are likely to be involved in the mechanism of cell
      death. CONCLUSIONS: Accumulation of COM crystals in the kidney is responsible for
      producing the renal toxicity associated with EG poisoning. The development of a
      pharmacological approach to reduce COM crystal adherence to tubular cells and its
      cellular interactions would be valuable as this would decrease the renal toxicity
      not only in late treated cases of EG poisoning, but also in other hyperoxaluric
      diseases such as primary hyperoxaluria and kidney stone formation.

PMID- 19852622
TI  - Retrograde transport of a traditional Chinese medicine, alpha-trichosanthin, and
      its selective neural toxicity.
AB  - OBJECTIVE: To investigate the peripheral neuronal toxicity of a traditional
      Chinese medicine, alpha-trichosanthin (TCS). METHODS: TCS and rhodamine
      conjugated TCS were separately injected into the rat sciatic nerve. Saline and
      rhodamine were used alone and separately as control solutions. The motor neurons
      in the spinal cord and sensory neurons in the dorsal root ganglia were separately
      counted. The entry of TCS molecules into neurons was observed under the
      fluorescence microscope. The glial reactions were studied by lectin staining and
      immunohistochemical method. The muscles innervated by the sciatic nerve and
      distal to the injection sites, and the nerves proximal to the injection sites
      were also collected and examined. RESULTS: TCS was taken up and transported by
      peripheral axons, and at a dose of 1 nmol, killed more than 90% of the motor
      neurons in 5 days, but only one-third of the sensory neurons of the injected
      nerve. The loss of neurons was permanent, while the increase of glial activities
      was mild and transient. CONCLUSION: TCS is retrogradely transported by axons of
      the injected nerve. TCS shows a selective neurotoxicity on different types of
      neurons. Hence TCS is useful in producing neural lesion in research, and this use
      may also be of applicational value in treating chronic spasticity, hyperalgesia,
      and pain.

PMID- 19852623
TI  - DMPS can reverse the features of severe mercury vapor-induced neurological
      damage.
AB  - CASE REPORT: A 36-year-old jewelry producer presented with tremor, slurred
      speech, lethargy, headache, and incoordination. On examination he had a coarse
      tremor of the outstretched hands and protruded tongue, slurred speech, "Hatter's
      shakes" handwriting, impaired heel-toe walking and heel-shin coordination, mild
      dysdiadochokinesis, and constricted visual fields to confrontation. The patient
      received four 5-day courses of oral 2,3-dimercapto-1-propanesulfonate (30
      mg/kg/day), which was associated with substantial objective clinical improvement
      and the excretion of 99,406 microg mercury. CONCLUSION: We recommend that the
      administration of 2,3-dimercapto-1-propanesulfonate should be considered in
      symptomatic patients who have been exposed to mercury vapor and who have
      supporting analytical confirmation of the diagnosis.

PMID- 19852624
TI  - Death in a toddler following endosulfan ingestion.
AB  - INTRODUCTION: Endosulfan, an organochlorine insecticide widely used in
      agriculture, is rapidly absorbed following ingestion, inhalation, or skin
      exposure. Poisonings rarely result in morbidity and mortality. Symptoms occur
      rapidly following exposure with CNS toxicity. Endosulfan has been banned in many
      countries; however, it is still used in the United States. CASE REPORT: A 2.5
      year-old ingested an unknown amount of endosulfan from a 20-ounce soft drink
      bottle. He immediately developed generalized tonic-clonic seizure activity and
      became unresponsive. He was transferred to the local hospital and to a tertiary
      children's hospital where the seizures were refractory to treatment despite
      treatment with multiple anticonvulsants. He became hypotensive requiring
      vasopressors. On day 3, an MRI showed cerebral edema, and a nuclear medicine flow
      scan failed to show blood flow to the brain and he was pronounced dead.
      DISCUSSION: This is the first published pediatric death in the United States
      because of endosulfan. Central nervous system stimulation is frequently the
      presenting symptom with or without other organ dysfunction. Status epilepticus
      causes the highest morbidity and mortality, therefore prompt administration of
      anticonvulsant drugs is important although not always effective. The child is our
      case demonstrated the most severe features of endosulfan exposure. CONCLUSION: In
      summary, prevention of a potentially toxic exposure is critical. The presence of
      this substance in a soft drink bottle contributed to the toxic exposure in this
      child, thus emphasizing the need for poison prevention education. The severe
      toxicity to those exposed raises the question of the need of this compound on the
      U.S. market.

PMID- 19852633
TI  - Long-term effects of rapid maxillary expansion followed by fixed appliances.
AB  - OBJECTIVE: To evaluate the long-term changes in maxillary arch widths, overjet,
      and overbite in patients who were treated with rapid maxillary expansion (RME)
      followed by edgewise appliances. MATERIALS AND METHODS: The material for the
      study consisted of study casts taken from 41 patients (19 males, 22 females) on
      four different occasions (before treatment, T1; after RME, T2; after treatment,
      T3; and during follow-up period, T4). The upper intercanine, interpremolar, and
      intermolar widths and overjet and overbite were measured on each set of study
      casts. Mean age of the subjects was 13.2 +/- 1.3 years (range, 11.2-16.9 years)
      at T1, 13.3 +/- 1.3 years (range, 11.3-17 years) at T2, 15.5 +/- 1.4 years
      (range, 13.1-18.8 years) at T3, and 20.4 +/- 1.6 years (range, 17.9-24.8 years)
      at T4. RESULTS: The net increase in intercanine width, interpremolar width,
      intermolar width, overjet, and overbite was 1.4 +/- 2.4 mm, 4.6 +/- 2.6 mm, 4.3
      +/- 2.5 mm, 0.1 +/- 0.6 mm, and 0.2 +/- 0.6 mm, respectively, and the relapse
      rates were 37% for intercanine width, 19% for interpremolar width, and 17% for
      intermolar width at the end of the follow-up period. CONCLUSIONS: A significant
      amount of relapse occurred in maxillary arch widths at the postretention
      assessment, the greatest being in intercanine width. RME significantly decreased
      overbite and increased overjet, and a statistically significant decrease was
      observed in both overbite and overjet at the postretention assessment.

PMID- 19852634
TI  - Long-term dentoskeletal effects and facial profile changes induced by bionator
      therapy.
AB  - OBJECTIVE: To evaluate the long-term skeletal and soft tissue changes induced by
      the bionator in Class II subjects. MATERIALS AND METHODS: The treatment sample
      consisted of 20 Class II patients (6 males and 14 females) treated consecutively
      with the bionator. The sample was evaluated at T1, start of treatment; T2, end of
      bionator therapy; and T3, long-term observation (including fixed appliances).
      Mean age at the start of treatment was 10 years 2 months (T1); at posttreatment,
      12 years 4 months (T2); and at long-term follow-up, 18 years 11 months (CS 6).
      The control group consisted of 20 subjects (8 males and 12 females) with
      untreated Class II malocclusions. Lateral cephalograms were analyzed at the three
      time points for all groups. Student's t-tests were used for comparisons of
      starting forms, and of the T1-T2 and T1-T3 changes between groups. RESULTS: The
      bionator group showed significant, favorable T1-T2 changes both at the skeletal
      and dentoalveolar levels. The vertical dimension was increased. Significant
      modifications were assessed for the soft tissues as well. The treated group
      showed a final improvement in soft tissue pogonion of about 2.5 mm. Significant
      mandibular changes were noted in the treated group, with a net average 3.3 mm
      long-term increase in mandibular length compared with untreated Class II
      controls. CONCLUSIONS: This study suggests that bionator treatment of Class II
      malocclusion maintains favorable results over the long-term with a combination of
      skeletal, dentoalveolar, and soft tissue changes.

PMID- 19852635
TI  - Long-term dentoskeletal changes with the Bionator, Herbst, Twin Block, and MARA
      functional appliances.
AB  - OBJECTIVE: To determine if the long-term dentoskeletal changes in patients
      treated with tooth-borne functional appliances were comparable to each other and
      to matched controls. MATERIALS AND METHODS: The experimental sample consisted of
      80 consecutively treated patients who were equally divided into Bionator, Herbst,
      Twin Block, and mandibular anterior repositioning appliance (MARA) groups. The
      control group comprised 21 children with untreated skeletal Class II
      malocclusions. Lateral cephalograms were taken for the treated group at T1
      (initial records), T2 (completion of functional therapy), and T3 (completion of
      fixed appliance therapy). A repeated measure analysis of variance (ANOVA) was
      used to assess the differences between and within groups. If ANOVA results were
      significant, Tukey-Kramer tests were used to determine where the significant
      differences occurred. RESULTS: (1) Temporary restriction of maxillary growth was
      found in the MARA group (T2-T1). (2) SNB increased more with the Twin Block and
      Herbst groups when compared with the Bionator and MARA groups. (3) The occlusal
      plane significantly changed in the Herbst and Twin Block groups. (4) The Twin
      Block group expressed better control of the vertical dimension. (5) The overbite,
      overjet, and Wits appraisal decreased significantly with all of the appliances.
      (6) The Twin Block group had significant flaring of the lower incisors at the end
      of treatment. (7) Over the long-term, there were no significant soft tissue
      changes among treated and untreated subjects. CONCLUSIONS: No significant
      dentoskeletal differences were observed long-term, among the various treatment
      groups and matched controls.

PMID- 19852636
TI  - Five years of sleep apnea treatment with a mandibular advancement device. Side
      effects and technical complications.
AB  - OBJECTIVE: To determine the variation in prevalence of temporomandibular
      disorders (TMD), other side effects, and technical complications during 5 years
      of sleep apnea treatment with a mandibular advancement device. MATERIALS AND
      METHODS: Forty patients diagnosed with obstructive sleep apnea received an
      adjustable appliance at 70% of the maximum protrusion. The protrusion was then
      progressively increased. TMD (diagnosed according to the Research Diagnostic
      Criteria for TMD), overjet, overbite, occlusal contacts, subjective side effects,
      and technical complications were recorded before and a mean of 14, 21, and 58
      months after treatment and analyzed by the Wilcoxon test (P < .05). RESULTS:
      Fifteen patients still used the oral appliance at the 5-year follow-up, and no
      significant variation in TMD prevalence was observed. Subjective side effects
      were common, and a significant reduction was found in overjet, overbite, and in
      the number of occlusal contacts. Furthermore, the patients made a mean of 2.5
      unscheduled dental visits per year and a mean of 0.8 appliance repairs/relines
      per year by a dental technician. The most frequent unscheduled visits were needed
      during the first year and were a result of acrylic breakage on the lateral
      telescopic attachment, poor retention, and other adjustments to improve comfort.
      CONCLUSIONS: Five-year oral appliance treatment does not affect TMD prevalence
      but is associated with permanent occlusal changes in most sleep apnea patients
      during the first 2 years. Patients seek several unscheduled visits, mainly
      because of technical complications.

PMID- 19852637
TI  - Facial profile shape, malocclusion and palatal morphology in Malay obstructive
      sleep apnea patients.
AB  - OBJECTIVE: To test the null hypothesis that there is no difference in facial
      profile shape, malocclusion class, or palatal morphology in Malay adults with and
      without obstructive sleep apnea (OSA). MATERIALS AND METHODS: Subjects were 120
      adult Malays aged 18 to 65 years (mean +/- standard deviation [SD], 33.2 +/-
      13.31) divided into two groups of 60. Both groups underwent clinical examination
      and limited channel polysomnography (PSG). The mean OSA and control values were
      subjected to t-test and the chi square test. RESULTS: Physical examination showed
      that 61.7% of the OSA patients were obese, and 41.7% of those obese patients had
      severe OSA. The mean body mass index (BMI) was significantly greater for the OSA
      group (33.2 kg/m2 +/- 6.5) than for the control group (22.7 kg/m2 +/- 3.5; P <
      .001). The mean neck size and systolic blood pressure were greater for the OSA
      group (43.6 cm +/- 6.02; 129.1 mm Hg +/- 17.55) than for the control group (35.6
      cm +/- 3.52; 114.1 mm Hg +/- 13.67; P < .001). Clinical examination showed that
      the most frequent findings among OSA groups when compared with the control group
      were convex profiles (71.7%), Class II malocclusion (51.7%), and V palatal shape
      (53.3%), respectively; the chi square test revealed a significant difference in
      terms of facial profile and malocclusion class (P < .05), but no significant
      difference in palatal shape was found. CONCLUSION: The null hypothesis is
      rejected. A convex facial profile and Class II malocclusion were significantly
      more common in the OSA group. The V palatal shape was a frequent finding in the
      OSA group.

PMID- 19852638
TI  - Psychological status of patients referred for orthognathic correction of skeletal
      II and III discrepancies.
AB  - OBJECTIVE: To establish the extent of psychological problems among patients who
      require orthognathic treatment. MATERIALS AND METHODS: Five aspects of
      psychological functioning were assessed for 162 patients who required
      orthognathic treatment and compared with 157 control subjects. RESULTS: Analysis
      of variance did not detect any significant difference in the five psychological
      scores recorded for the skeletal II, skeletal III, and control groups. The
      proportion of subjects with one or more psychological measure beyond the normal
      range was 27% for skeletal II subjects, 25% for skeletal III subjects, and 26%
      for control subjects. One skeletal II subject (1.5%), three skeletal III subjects
      (3%), and five control subjects (3%) required referral for psychological
      counseling. CONCLUSIONS: The orthognathic patients did not differ significantly
      from the control subjects in their psychological status.

PMID- 19852639
TI  - Fixed orthodontic appliance therapy and its impact on oral health-related quality
      of life in Chinese patients.
AB  - OBJECTIVE: To determine changes in oral health-related quality of life (OHRQoL)
      during fixed orthodontic appliance therapy in Chinese patients. MATERIALS AND
      METHODS: Two-hundred fifty Chinese orthodontic patients completed six distinct
      intervals of the 14-item Oral Health Impact Profile (OHIP-14, Chinese version):
      before treatment (T0); after the placement of the fixed appliance at 1 week (T1),
      1 month (T2), 3 months (T3), and 6 months (T4); and posttreatment (T5). RESULTS:
      The overall response rate was 88.8% (222 of 250). Significant differences of
      overall OHIP-14 scores could be found between any two time points (P < .001),
      except for between T0 and T2 (P > .05) and between T3 and T4 (P > .05). Overall
      scores at T1 were significantly higher than the scores at the other intervals (P
      < .001), with a significant change in the scores on physical pain (P < .001),
      psychological discomfort (P < .001), and physical disability (P < .001). Scores
      at T5 were lowest among the six time points (P < .001). CONCLUSIONS: Fixed
      orthodontic appliance therapy did affect Chinese patients' OHRQoL. Patients were
      considerably compromised in terms of their overall OHRQoL until approximately 1
      month after insertion. The severity of the compromised condition in terms of
      overall OHRQoL was greatest at 1 week with the reported impact on physical pain,
      psychological discomfort, and physical disability. Patients' OHRQoL was better
      after they completed the orthodontic treatment than before or during treatment.

PMID- 19852640
TI  - Duration of the pubertal peak in skeletal Class I and Class III subjects.
AB  - OBJECTIVE: To estimate and compare the duration of the pubertal growth peak in
      Class I and Class III subjects. MATERIALS AND METHODS: The data examined
      consisted of pretreatment lateral cephalometric records of 218 skeletal Class I
      or Class III subjects (93 female and 125 male subjects) of white ancestry. The
      duration of the pubertal peak was calculated from the average chronological age
      intervals between stages CS3 and CS4 of the cervical vertebral maturation in
      Class I vs Class III groups (t-test). RESULTS: In skeletal Class I subjects, the
      pubertal peak had a mean duration of 11 months, whereas in Class III subjects it
      lasted 16 months. The average difference (5 months) was statistically significant
      (P < .001). CONCLUSIONS: The growth interval corresponding to the pubertal growth
      spurt (CS3-CS4) was longer in Class III subjects than in subjects with normal
      skeletal relationships; the larger increases in mandibular length during the
      pubertal peak reported in the literature for Class III subjects may be related to
      the longer duration of the pubertal peak.

PMID- 19852641
TI  - Soft tissue images from cephalograms compared with those from a 3D surface
      acquisition system.
AB  - OBJECTIVE: To assess whether 2D cephalometrics is comparable with 3D imaging
      devices and whether 3D technology could replace traditional 2D image capture in
      posttreatment evaluation. MATERIALS AND METHODS: The study is a prospective
      evaluation of superimposition techniques obtained from a cohort of 40 patients
      who underwent orthognathic surgery in a private practice environment. Surgical
      records were obtained from lateral cephalometric radiographs taken by a Kodak
      8000C machine, and the 3D images were obtained from the 3dMD stereo
      photogrammetric camera capture system. Pre- and postlateral cephalometric records
      were superimposed on the cranial base (SN line) while pre- and post-3D surgical
      records were superimposed on the regional best-fit method. A mathematical
      algorithm, or best-fit calculation, was carried out on the selected surfaces.
      Each set of superimposed records was analyzed, and five soft tissue landmarks
      were plotted. The differences between the five surface points were analyzed for
      each set of records. RESULTS: The final sample consisted of 34 subjects with full
      records. A total of 680 surface landmarks were plotted and analyzed. The mean
      differences of the soft tissue landmarks were analyzed for each pair of data sets
      and were found to range between 1.06 and 8.07 mm and 1.26 and 7.34 mm for lateral
      cephalometric and 3D readings, respectively. Paired t-tests were carried out
      using the SPSS 15.0 software, and they showed that the results were not
      statistically significant between the superimposition techniques on the image
      capture systems (P > .05). CONCLUSIONS: The types of superimposition techniques
      used in the imaging modalities studied were comparable with one another.

PMID- 19852642
TI  - Functional occlusal patterns and their relationship to static occlusion.
AB  - OBJECTIVES: To test the hypothesis that there is no relationship between static
      occlusion and dynamic occlusion. MATERIALS AND METHODS: The relationship between
      static and dynamic occlusion was investigated in a sample of 94 dental students
      (39 males and 55 females) with an age range of 21-30 years. Static occlusion was
      determined by intraoral examination. Dynamic occlusion was determined in
      regulated lateral (0.5 mm and 3 mm lateral to the intercuspal position) and
      protrusive movements of the mandible by intraoral examination with the aid of
      shimstock. RESULTS: At the 0.5 mm lateral excursion, 24.5% had bilateral group
      function and 12.7% had bilateral canine guidance. At the 3 mm positions, the
      guidance pattern changed to a predominantly canine guidance. Fifty percent of
      subjects had bilateral canine guidance, and only 8.8% had bilateral group
      function. In terms of the anterior guidance pattern, a predominant anterior
      contact with posterior disocclusion (77.5%) was noted. Examination of the
      relationship between static and dynamic occlusions revealed that at the 0.5 mm
      position, the pattern of dynamic occlusion was different in relation to various
      static occlusion features but without reaching a significant level. While at the
      3 mm position, the pattern of dynamic occlusion was significantly affected by
      incisor relationship. The distribution of protrusive excursion patterns was
      significantly influenced by incisor, canine, and molar relationships.
      CONCLUSIONS: The hypothesis is rejected. An association exists between dynamic
      occlusion and different aspects of static occlusion.

PMID- 19852643
TI  - Maximum closing force of mentolabial muscles and type of malocclusion.
AB  - OBJECTIVE: To measure the closing force of the upper and lower lips and to
      ascertain the relationship between the maximum closing force of the mentolabial
      muscles and types of malocclusion. MATERIALS AND METHODS: Of those who showed the
      full eruption of a second molar and no permanent tooth loss, 99 subjects were
      chosen who showed a positive overbite and ANB and no skeletal asymmetry. By using
      the Y-meter, which can measure the lip force in the vertical direction using a
      load cell, the closing forces of the upper and lower lips were measured
      separately. A one-way analysis of variance (ANOVA) test and the Pearson's
      correlation test were used to evaluate the interrelationship between lip force
      and dentofacial morphology. RESULTS: The lip closing force was greater in male
      and Class I subjects. Upper lip force was greater than that of the lower lip in
      all groups. The values of lip closing forces were related to the variables of
      upper incisor angulation. In Class II subjects, the values of lip closing forces
      were also related to the vertical skeletal pattern. CONCLUSIONS: The mentolabial
      muscle force was highly correlated with dentofacial structure and types of
      malocclusion.

PMID- 19852645
TI  - Cephalometric characteristics of Korean children with Class III malocclusion in
      the deciduous dentition.
AB  - OBJECTIVE: To compare the cephalometric characteristics of children with Class
      III malocclusion to those of children with normal occlusion during the deciduous
      dentition phase. MATERIALS AND METHODS: Cephalometric measurements of 27 children
      (mean age: 5.03 years) diagnosed with Class III malocclusion were compared with
      32 children (mean age: 4.85 years) diagnosed with normal occlusion in the
      following four categories: sagittal skeletal analysis, vertical skeletal
      analysis, dentoalveolar analysis, and soft tissue analysis. RESULTS: Significant
      differences were seen in all categories except vertical skeletal analysis.
      Sagittal skeletal measurements included ANB (Class III group: -0.91 +/- 1.60;
      normal group: 5.28 +/- 1.29), facial convexity (Class III group: 0.47 +/- 4.32;
      normal group: 13.65 +/- 3.44), Wits appraisal (Class III group: -5.54 +/- 2.36;
      normal group: -0.84 +/- 1.91), and A to N-perpendicular (Class III group: -2.94
      +/- 3.05; normal group: 0.78 +/- 2.53). Dentoalveolar measurements included U1 to
      NA (Class III group: 11.98 +/- 5.25; normal group: 8.12 +/- 5.43), IMPA (Class
      III group: 81.34 +/- 7.40; normal group: 86.57 +/- 5.67), and interincisal angle
      (Class III group: 152.65 +/- 8.82; normal group: 145.03 +/- 7.34). Soft tissue
      measurements included soft tissue convexity (Class III group: 2.47 +/- 4.20;
      normal group: 12.71 +/- 3.95), nasofacial angle (Class III group: 22.68 +/- 4.22;
      normal group: 26.24 +/- 3.84), and upper lip to esthetic plane (Class III group: 
      0.65 +/- 2.74; normal group: 3.07 +/- 1.90). CONCLUSIONS: There are significant
      differences between the craniofacial patterns of normal children and those of
      children with Class III malocclusion that can be identified with cephalometric
      analysis as early as the deciduous dentition phase.

PMID- 19852644
TI  - Soft tissue morphology of Jordanian adolescents.
AB  - OBJECTIVE: To determine soft tissue cephalometric norms of a sample of Jordanian
      adolescents and to compare them with those of North Americans. MATERIALS AND
      METHODS: Forty-one subjects aged 14 to 17 years were selected from a larger
      random and representative sample of 320 adolescents attending 12 schools in the
      capital of Jordan, Amman. Seven reference lines were identified and traced
      according to definitions by Holdaway and Ricketts, and 2 angular and 12 linear
      measurements were analyzed. RESULTS: Significant differences were found between
      males and females in measurements of soft tissue facial angle, H angle, subnasale
      to H line, basic upper lip thickness, upper lip thickness and labrale inferius
      and superius to E line (P < .05). Males had a more prominent upper lip in
      relation to the overall soft tissue profile, while the lips of females were
      considerably more retrusive in relation to the nose and chin. Jordanian norms
      were similar to those of North Americans, with only two exceptions: the H angle
      and skeletal convexity which were 5.4 degrees and 3.2 mm greater in Jordanians,
      respectively. CONCLUSIONS: Jordanian soft tissue norms were similar to American
      norms with the exception of the former having a more prominent upper lip position
      in relation to the overall soft tissue profile.

PMID- 19852646
TI  - Skeletal and soft tissue point A and B changes following orthodontic treatment of
      Nepalese Class I bimaxillary protrusive patients.
AB  - OBJECTIVES: To test the hypothesis that there is no correlation in the
      interrelationships of skeletal and soft tissue points A and B with anterior teeth
      retraction. MATERIALS AND METHODS: Thirty adult Class I bimaxillary protrusion
      patients treated with preadjusted appliances after first premolar extraction were
      included. Pretreatment and posttreatment variables were compared using paired t
      test, and the relationship of soft and hard tissue variables was studied using
      Pearson correlation coefficient and linear regression equation. RESULTS: Mean
      point A and soft tissue point A (sA) were retracted 2.7 mm (P < .001) and 1.7 mm
      (P < .001), and mean point B and soft tissue point B (sB) were retracted 2.1 mm
      (P < .001) and 1.2 mm (P < .001), respectively. Mean ratio of retraction of point
      A with sA and point B with sB was 1.5:1 and 1.7:1, respectively. A significant
      degree of correlation existed between retraction of point A and soft tissue point
      A (r = 0.648, P < .01) and point B and soft tissue point B (r = 0.806, P < .01).
      Linear regression analysis used to predict the changes in sA and sB showed
      significant relationship between point A and sA (r = 0.543, F = 11.7, R2 = 0.29,
      P < .001) and point B and sB (r = 0.825, F = 59.7, R2 = 0.68, P < .001).
      Decreases in hard and soft tissue convexity were due to the retraction of the
      skeletal and soft tissue points A and B in addition to the lips retraction.
      CONCLUSIONS: The hypothesis is rejected. Retraction of skeletal point A and B
      lead to retraction of sA and sB under controlled root positions. Nearly
      proportionate changes existed in the skeletal points and overlying corresponding
      soft tissue points.

PMID- 19852647
TI  - Mandibular growth, remodeling, and maturation during infancy and early childhood.
AB  - OBJECTIVE: To describe the growth, maturation, and remodeling changes of the
      mandible during infancy and early childhood. MATERIALS AND METHODS: Seven Bolton
      Brush Growth Study longitudinal cephalograms (N = 336) of each of 24 females and
      24 males, taken between birth and 5 years of age, as well as early adulthood,
      were traced and digitized. Five measurements and nine landmarks were used to
      characterize mandibular growth, remodeling, and degree of adult maturity.
      RESULTS: Overall, mandibular length showed the greatest growth changes, followed
      by ramus height and corpus length. Corpus length was the most mature of the three
      linear measures; ramus height was less mature than overall mandibular length. The
      greatest growth rates occurred between 0.4-1 year; yearly velocities decelerated
      thereafter. The ramus remodeled superiorly only slightly more than it remodeled
      posteriorly. Male mandibles were significantly (P < or = .05) larger, displayed
      greater growth rates, and were significantly less mature than female mandibles.
      There were no significant differences in mandibular growth or maturation between
      Class I and Class II patients. CONCLUSIONS: The mandible displays decelerating
      rates of growth and a maturity gradient during infancy and early childhood, with
      males showing more growth and being more mature than females.

PMID- 19852648
TI  - Rapid maxillary expansion affects the spheno-occipital synchondrosis in
      youngsters. A study with low-dose computed tomography.
AB  - OBJECTIVE: To test the null hypothesis that the spheno-occipital synchondrosis
      does not show bony displacement in response to rapid maxillary expansion (RME)
      therapy in youngsters. MATERIALS AND METHODS: A total of 16 computed tomography
      (CT) records were taken from 8 growing patients (2 males and 6 females), before
      (T0) and after (T1) treatment with RME. All patients had been diagnosed
      originally with transverse maxillary deficiency. The mean chronological age of
      the patients was 9.8 +/- 1.8 years (range, 8 to 11.4 years). High-resolution
      multislice multidetector CT was used to study quantitatively the extent of the
      opening of the spheno-occipital synchondrosis following RME. A low-dose CT scan
      protocol was used (80 kV, 10 mA) and the data file of each patient was
      transferred to a workstation where the anteroposterior width of the spheno
      occipital synchondrosis was measured on axial images. RESULTS: Before treatment
      with RME (T0), the anteroposterior mean width of the spheno-occipital
      synchondrosis was 1.73 +/- 0.46 mm immediately after the active phase of
      expansion (T1), and the width of the synchondrosis increased to 2.30 +/- 0.47.
      This difference was statistically significant according to the Wilcoxon signed
      rank test (P < .05). CONCLUSION: Rapid maxillary expansion leads to a small
      immediate widening of the spheno-occipital synchondrosis in youngsters.

PMID- 19852649
TI  - Tooth movement activates the central amygdala and the lateral hypothalamus by the
      magnitude of the force applied.
AB  - OBJECTIVE: To determine if the magnitude of the force used to induce incisor
      tooth movement promotes distinct activation in cells in the central amygdala
      (CEA) and lateral hypothalamus (LH) of rats. Also, the effect of morphine on Fos
      immunoreactivity (Fos-IR) was investigated in these nuclei. MATERIALS AND
      METHODS: Adult male rats were anesthetized and divided into six groups: only
      anesthetized (control), without orthodontic appliance (OA), OA but without force,
      OA activated with 30g or 70g, OA with 70g in animals pretreated with morphine (2
      mg/kg, intraperitoneal). Three hours after the onset of the experiment the rats
      were reanesthetized and perfused with 4% paraformaldehyde. The brains were
      removed and fixed, and sections containing CEA and LH were processed for Fos
      protein immunohistochemistry. RESULTS: The results show that in the control
      group, the intramuscular injection of a ketamine/ xylazine mixture did not induce
      Fos-IR cells in the CEA or in the LH. Again, the without force group showed a
      little Fos-IR. However, in the 70g group the Fos-IR was the biggest observed (P <
      .05, Tukey) in the CEA and LH compared with the other groups. In the 30g group,
      the Fos-IR did not differ from the control group, the without OA group, and the
      without force group. Furthermore, pretreatment with morphine in the 70g group
      reduced Fos-IR in these regions. CONCLUSIONS: Tooth movement promotes Fos-IR in
      the CEA and LH according to the magnitude of the force applied.

PMID- 19852650
TI  - Effects of low-level laser therapy and orthodontic tooth movement on dental pulps
      in rats.
AB  - OBJECTIVES: To describe the microscopic pulpal reactions resulting from
      orthodontically induced tooth movement associated with low-level laser therapy
      (LLLT) in rats. MATERIALS AND METHODS: Forty-five young male Wistar rats were
      randomly assigned to three groups. In group I (n = 20), the maxillary right first
      molars were submitted to orthodontic movement with placement of a coil spring. In
      group II (n = 20), the teeth were submitted to orthodontic movement plus LLLT at
      4 seconds per point (buccal, palatal, and mesial) with a GaAlAs diode laser
      source (830 nm, 100 mW, 18 J/cm(2)). Group III (n = 5) served as a control (no
      orthodontic movement or LLLT). Groups I and II were divided into four subgroups
      according to the time elapsed between the start of tooth movement and sacrifice
      (12 hours, 24 hours, 3 days, and 7 days). RESULTS: Up until the 3-day period, the
      specimens in group I presented a thicker odontoblastic layer, no cell-free zone
      of Weil, pulp core with differentiated mesenchymal and defense cells, and a high
      concentration of blood vessels. In group II, at the 12- and 24-hour time points,
      the odontoblastic layer was disorganized and the cell-free zone of Weil was
      absent, presenting undifferentiated cells, intensive vascularization with
      congested capillaries, and scarce defense cells in the cell-rich zone. In groups
      I and II, pulpal responses to the stimuli were more intense in the area
      underneath the region of application of the force or force/laser. CONCLUSIONS:
      The orthodontic-induced tooth movement and LLLT association showed reversible
      hyperemia as a tissue response to the stimulus. LLLT leads to a faster repair of
      the pulpal tissue due to orthodontic movement.

PMID- 19852651
TI  - Resistance to immediate orthodontic loading of surface-treated mini-implants.
AB  - OBJECTIVE: To test the hypothesis that there is no difference in the stability
      and resistance to orthodontic forces of immediately loaded sandblasted and acid
      etched (SAE) mini-implants and those of machined-surface implants of the same
      size and shape. MATERIALS AND METHODS: Two types of mini-implants were used in
      the tibiae of 44 rabbits; some had an SAE surface and some had machined surfaces.
      Orthodontic loading of 150 g was applied immediately after placement. The success
      rates and maximum removal torque values (RTVs) of 412 mini-implants were recorded
      and compared immediately after placement, 3 days after placement, and 1, 6, and
      10 weeks after placement. The RTV data were analyzed using multiple regression
      analysis to evaluate differences with respect to surface treatment, loading, and
      loading periods (P < .05). Multiple comparisons using the Scheffe method were
      performed to evaluate the RTVs for the subsequent loading periods. RESULTS:
      Thirteen mini-implants failed during the experimental period. The SAE group had a
      higher RTV than the machined group, and there was significant difference in RTVs
      in accordance with loading periods (P < .001). However, there was no significant
      RTV difference between loaded and unloaded mini-implants. CONCLUSIONS: The
      hypothesis was supported. Both SAE mini-implants and machined mini-implants can
      be loaded immediately and experience similar success rates. RTVs were higher for
      the SAE mini-implants than for the machined mini-implants. The latter finding
      suggests that, for immediate loading, SAE mini-implants may provide more stable
      retention than machined mini-implants.

PMID- 19852652
TI  - Root contact during drilling for microimplant placement. Affect of surgery site
      and operator expertise.
AB  - OBJECTIVE: To determine the surgery site dependency of root contact during
      drilling for orthodontic microimplant placement and to analyze the influence of
      clinicians' expertise on the results. MATERIALS AND METHODS: Dental arches with
      resin teeth were mounted on a dental phantom (P-5/3 TS, Frasaco, Germany).
      Drilling was conducted in six locations frequently selected for microimplant
      placement: between the central incisors, between the maxillary first molar and
      second premolar, and between the mandibular first and second molars, bilaterally.
      The 28 qualified dentists who participated were divided into two groups based on
      their clinical experience. A total of 192 drillings were performed by the
      experienced group and 240 by the inexperienced group. The damaged root surfaces
      were classified as "moderate" or "severe." RESULTS: Significant differences in
      both overall and site-dependent rates of root contacts were found between the
      groups. Overall rates for the experienced and inexperienced groups were 13.5% and
      21.3%, respectively. For the experienced group, the incidents occurred
      predominantly in the lower left (34.4%) and upper right (18.8%) posterior
      regions. The most susceptible teeth were numbers 36 and 16. In contrast, for the
      inexperienced group, all four posterior regions were susceptible. CONCLUSIONS:
      The surgery site and clinicians' expertise had significant effects on the rate as
      well as the pattern of root contacts.

PMID- 19852653
TI  - Palatal bone density in adult subjects: implications for mini-implant placement.
AB  - OBJECTIVES: To evaluate palatal bone density to allow for better selection of
      palatal implant anchorage sites. MATERIALS AND METHODS: Computed tomographic (CT)
      images were obtained from 15 males and 15 females (mean age, 27 years; range, 23
      35 years). Bone density was measured in Hounsfield units (HU) at 80 coordinates
      at regular mediolateral and anteroposterior intervals along the midpalatal
      suture. RESULTS: Bone densities ranged from 805 to 1247 HU. A significant
      difference between male and female groups was noted, although no difference was
      found between left and right sides of individual palates. Palatal bone densities
      showed a tendency to decrease laterally and posteriorly. The midpalatal area
      within 3 mm of the midsagittal suture had the densest bone in the entire palate.
      CONCLUSION: Results suggest that mini-implants for orthodontic anchorage may be
      effectively placed in most areas with bone density equivalent to the palatal area
      if they are placed from 3 mm posterior to the incisive foramen and 1 to 5 mm to
      the paramedian side.

PMID- 19852654
TI  - Optimal palatal configuration for miniscrew applications.
AB  - OBJECTIVE: To test the hypothesis that palatal bone is not able to support
      titanium miniscrews (11 mm in length and 2 mm in diameter) when subjected to
      forces normally generated during orthodontic treatment. MATERIALS AND METHODS:
      The miniscrew-palatal bone system was modeled and analyzed using the commercial
      finite element method software ANSYS Multiphysics 10.0; tests were done in both a
      state of total osseointegration and in the absence of it. Calculations were
      carried out in both cases in configurations where the miniscrew was inserted into
      two different palatal regions: in the first it was anchored in one layer of
      cortical bone and in the underlying trabecular bone; in the second, two layers of
      cortical bone and the trabecular bone in between were involved. Two different
      loads were taken into account, 240 gf and 480 gf, both of which are within the
      normal range for orthodontic treatment, and applied to the miniscrew heads.
      RESULTS: The results demonstrated that the miniscrew inserted into the palate can
      be anchored to bone and loaded within normal orthodontic force range without
      exceeding the stress levels that lead to bone fracture. The osseointegrated
      system was characterized by a lower level of stress than the nonosseointegrated
      one, but anchorage within the second layer of cortical bone markedly reduced the
      stress on the trabecular bone, thereby improving the stability of the implant,
      also in the absence of osseointegration. CONCLUSIONS: The hypothesis is rejected.
      Miniscrews loaded within the normal orthodontic force range do not exceed the
      stress levels that lead to bone fracture.

PMID- 19852655
TI  - Palatal volume following rapid maxillary expansion in mixed dentition.
AB  - OBJECTIVE: To evaluate volumetric variations in the palate following rapid
      expansion, both immediately after treatment and over time. MATERIALS AND METHODS:
      The sample was composed of 30 patients in early mixed dentition treated with a
      Haas-type device cemented onto the primary second molars. The mean age of the
      patients upon commencement of expansion was 7 years and 6 months (standard
      deviation [SD], 12 months). Measurement of palatal volume was conducted via 3D
      acquisition of plaster models using laser scanning before treatment (T1), upon
      device removal (T2), and 2.6 years afterward (T3). RESULTS: The volume of the
      palate increased in a statistically significant fashion from T1 to T2 and from T1
      to T3, and it decreased in a nonsignificant fashion from T2 to T3. CONCLUSIONS:
      Palatal volume significantly increases with rapid maxillary expansion (RME)
      treatment with insignificant relapse. The use of virtual 3D models with the aid
      of Apposite software permits evaluation of the morphologic and volumetric changes
      induced by orthodontic treatment.

PMID- 19852656
TI  - The validity of in vivo tooth volume determinations from cone-beam computed
      tomography.
AB  - OBJECTIVE: To determine the accuracy of volumetric analysis of teeth in vivo
      using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The physical
      volume (Vw) of 24 bicuspids extracted for orthodontic purposes (16 were imaged
      with the I-CAT and 8 with the CB MercuRay) were determined using the water
      displacement technique. Corresponding pretreatment CBCT image data were uploaded
      into Amira 4.0 for segmentation and radiographic volume (Va). All measurements
      were performed twice by two observers. The statistical difference between Vw and
      Va was assessed using a paired t-test. The intraobserver and interobserver
      reliability were determined by calculating Pearson correlation coefficients and
      intraclass correlation coefficients. RESULTS: The overall mean Vw of teeth
      specimens was 0.553 +/- 0.082 cm3, while the overall mean Va was 0.548 +/- 0.079
      cm3 (0.529 +/- 0.078 cm3 for observer 1 and 0.567 +/- 0.085 cm3 for observer 2).
      There were statistically significant differences between Va and Vw (P < .05).
      Between observer 1 and observer 2, Va measurements were statistically
      significantly different (P < .05). The interobserver and intraobserver
      correlation coefficient for Vw was high. Lastly, surface smoothing reduced the
      volume by 3% to 12%. CONCLUSIONS: In vivo determination of tooth volumes from
      CBCT data is feasible. The measurements slightly deviate from the physical
      volumes within -4% to 7%. Smoothing operations reduce volume measurements.
      Currently, no requirements for accuracy of volumetric determinations of tooth
      volume have been established.

PMID- 19852657
TI  - Porcelain surface alterations and refinishing after use of two orthodontic
      bonding methods.
AB  - OBJECTIVE: To compare porcelain surfaces at debonding after use of two surface
      preparation methods and to evaluate a method for restoring the surface. MATERIALS
      AND METHODS: Lava Ceram feldspathic porcelain discs (n = 40) underwent one of two
      surface treatments prior to bonding orthodontic brackets. Half the discs had
      sandblasting, hydrofluoric acid, and silane (SB + HF + S), and the other half,
      phosphoric acid and silane (PA + S). Brackets were debonded using bracket
      removing pliers, and resin was removed with a 12-fluted carbide bur. The surface
      was refinished using a porcelain polishing kit, followed by diamond polishing
      paste. Measurements for surface roughness (Ra), gloss, and color were made before
      bonding (baseline), after debonding, and after each step of refinishing. Surfaces
      were also examined by scanning electron microscopy (SEM). Data was analyzed with
      2-way ANOVA followed by Tukey HSD tests (alpha = 0.05). RESULTS: The SB + HF + S
      bonding method increased Ra (0.160 to 1.121 microm), decreased gloss (41.3 to
      3.7) and altered color (DeltaE = 4.37; P < .001). The PA + S method increased Ra
      (0.173 to 0.341 microm; P < .001), but the increase in Ra was significantly less
      than that caused by the SB + HF + S bonding method (P < . 001). The PA + S method
      caused insignificant changes in gloss (41.7 to 38.0) and color (DeltaE = 0.50).
      The measurements and SEM observations showed that changes were fully restored to
      baseline with refinishing. CONCLUSIONS: The PA + S method caused significantly
      less damage to porcelain than the SB + HF + S method. The refinishing protocol
      fully restored the porcelain surfaces.

PMID- 19852658
TI  - Physical properties of conventional and Super Slick elastomeric ligatures after
      intraoral use.
AB  - OBJECTIVE: To investigate the change in the physical properties of conventional
      and Super Slick elastomeric ligatures after they have been in the mouth.
      MATERIALS AND METHODS: Nine healthy volunteers took part. One orthodontic bracket
      was bonded to a premolar tooth in each of the four quadrants of the mouth. Two
      conventional and two Super Slick elastomeric ligatures were placed at random
      locations on either side of the mouth. The ligatures were collected after various
      time intervals and tested using an Instron Universal testing machine. The two
      outcome measures were failure load and the static frictional resistance. RESULTS:
      The failure load for conventional ligatures was reduced to 67% of the original
      value after 6 weeks in situ. Super Slick elastomeric ligatures showed a
      comparable reduction after 6 weeks in situ (63% of original value). There were no
      statistical differences in the static friction between conventional and Super
      Slick elastomerics that had been in situ for either 24 hours (P = .686) or 6
      weeks (P = .416). There was a good correlation between failure load and static
      friction (r = .49). CONCLUSIONS: There were statistically significant differences
      in the failure loads of elastomerics that had not be placed in the mouth and
      those that had been in the mouth for 6 weeks. There were no differences in the
      static frictional forces produced by conventional and Super Slick ligatures
      either before or after they had been placed in the mouth. There appears to be a
      direct proportional relationship between failure load and static friction of
      elastomeric ligatures.

PMID- 19852659
TI  - Forces of various nickel titanium closed coil springs.
AB  - OBJECTIVE: To compare the forces generated by 14 different 9 mm springs supplied
      by five different companies. MATERIALS AND METHODS: Five replicates of 14
      different 9 mm springs were evaluated, resulting in 70 total specimens. Each was
      extended once from its resting length to 12 mm and then was deactivated. All
      tests were performed in a 37 degrees C water bath. Forces were recorded at the 12
      mm extension and deactivation distances of 9 mm, 6 mm, 3 mm, and 1 mm using an
      MTS force gauge. Data were collected with Testworks software, version 4.0, and
      were analyzed by analysis of variance (ANOVA) with one factor alternated.
      RESULTS: Mean peak load forces at 12 mm were significantly different between
      springs, and these forces varied from 147 to 474 grams. Mean unload forces
      measured at 9 mm, 6 mm, and 3 mm of deactivation values were highly variable, and
      only 6 of the 14 springs exhibited a "physiologic" mean unload force of 50 grams
      or less over the total deactivation range. CONCLUSIONS: Few springs tested
      exhibited physiologic peak load forces and constant deactivation forces. This
      study suggests that labeling of nickel titanium closed coil springs is confusing
      and misleading.

PMID- 19852660
TI  - Self-ligation esthetic brackets with low frictional resistance.
AB  - OBJECTIVE: To test the frictional resistance forces (FRS) generated between
      several archwires and (1) interactive self-ligating (ISL) brackets and (2)
      conventionally ligated (CL) brackets. MATERIALS AND METHODS: Frictional forces
      produced between three different archwire combinations and self-ligating (SL)
      brackets (ceramic and metal-slot or all-metal) and CL brackets (metal or ceramic)
      were evaluated in a dry environment. The three ISL brackets tested were In
      Ovation-C, In-Ovation-R, and Damon 3. The three CL brackets were Mystique with
      Neo Clip, Clarity, and Ovation. Each bracket was tested with 0.020'' SS, 0.019''
      x 0.025'' SS and 0.018'' x 0.018'' coated SS. RESULTS: The ISL brackets generally
      exhibited the lowest frictional forces irrespective of the bracket material and
      the wire size, and CL brackets exhibited consistently higher frictional forces.
      Mystique with Neo Clip produced the lowest frictional resistance of all brackets.
      The In-Ovation-C brackets demonstrated significantly lower frictional resistance
      than the SL brackets In-Ovation-R and Damon 3 as well as the CL brackets Clarity
      and Ovation. CONCLUSIONS: The ISL ceramic brackets produced the lowest frictional
      resistance of all the self-ligating brackets. The CL ceramic brackets produced
      the greatest friction.

PMID- 19852661
TI  - Flowable composites for bonding orthodontic retainers.
AB  - OBJECTIVE: To test the null hypothesis that there are no statistically
      significant differences between flowables and an orthodontic adhesive tested in
      terms of shear bond strength (SBS) and pullout resistance. MATERIALS AND METHODS:
      To test the SBS of Light Bond, FlowTain, Filtek Supreme, and Tetric Flow were
      applied to the enamel surfaces of 15 teeth. Using matrices for application, each
      composite material was cured for 40 seconds and subjected to SBS testing. To test
      pullout resistance, 15 samples were prepared for each composite in which a wire
      was embedded; then the composite was cured for 40 seconds. Later, the ends of the
      wire were drawn up and tensile stress was applied until the resin failed.
      Findings were analyzed using an ANOVA and a Tukey HSD test. RESULTS: The SBS
      values for Light Bond, FlowTain, Filtek Supreme, and Tetric Flow were 19.0 +/-
      10.9, 14.7 +/- 9.3, 22.4 +/- 16.3, and 16.8 +/- 11.8 MPa, respectively, and mean
      pullout values were 42.2 +/- 13.0, 24.0 +/- 6.9, 26.3 +/- 9.4, and 33.8 +/- 18.0
      N, respectively. No statistically significant differences were found among the
      groups in terms of SBS (P > .05). On the other hand, Light Bond yielded
      significantly higher pullout values compared with the flowables Filtek Supreme
      and Flow-Tain (P < .01). However, there were no significant differences among the
      pullout values of flowables, nor between Light Bond and Tetric Flow (P > .05).
      CONCLUSIONS: The hypothesis is rejected. Light Bond yielded significantly higher
      pullout values compared with the flowables Filtek Supreme and FlowTain. However,
      flowable composites provided satisfactory SBS and wire pullout values, comparable
      to a standard orthodontic resin, and therefore can be used as an alternative for
      direct bonding of lingual retainers.

PMID- 19852662
TI  - Torque expression in stainless steel orthodontic brackets. A systematic review.
AB  - OBJECTIVE: To evaluate the quantitative effects on torque expression of varying
      the slot size of stainless steel orthodontic brackets and the dimension of
      stainless steel wire, and to analyze the limitations of the experimental methods
      used. MATERIALS AND METHODS: In vitro studies measuring torque expression in
      conventional and self-ligating stainless steel brackets with a torque-measuring
      device, with the use of straight stainless steel orthodontic wire without second
      order mechanics and without loops, coils, or auxiliary wires, were sought through
      a systematic review process. RESULTS: Eleven articles were selected. Direct
      comparison of different studies was limited by differences in the measuring
      devices used and in the parameters measured. On the basis of the selected
      studies, in a 0.018 inch stainless steel bracket slot, the engagement angle
      ranges from 31 degrees with a 0.016 x 0.016 inch stainless steel archwire to 4.6
      degrees with a 0.018 x 0.025 inch stainless steel archwire. In a 0.022 inch
      stainless steel bracket slot, the engagement angle ranges from 18 degrees with a
      0.018 x 0.025 inch stainless steel archwire to 6 degrees with a 0.021 x 0.025
      inch stainless steel archwire. Active stainless steel self-ligating brackets
      demonstrate an engagement angle of approximately 7.5 degrees, whereas passive
      stainless steel self-ligating brackets show an engagement angle of approximately
      14 degrees with 0.019 x 0.025 inch stainless steel wire in a 0.022 inch slot.
      CONCLUSIONS: The engagement angle depends on archwire dimension and edge shape,
      as well as on bracket slot dimension, and is variable and larger than published
      theoretical values. Clinically effective torque can be achieved in a 0.022 inch
      bracket slot with archwire torsion of 15 to 31 degrees for active self-ligating
      brackets and of 23 to 35 degrees for passive self-ligating brackets with a 0.019
      x 0.025 inch stainless steel wire.

PMID- 19852663
TI  - Soft tissue changes following the extraction of premolars in nongrowing patients
      with bimaxillary protrusion. A systematic review.
AB  - OBJECTIVE: To quantify the amount of perioral tissue changes following the
      extraction of four premolars in patients with bimaxillary protrusion who had
      nearly completed active growth. MATERIALS AND METHODS: A literature search was
      conducted to identify clinical trials that assessed cephalometric perioral soft
      tissue changes in patients affected by biprotrusion and treated with extractions.
      Electronic databases (PubMed, ISI WoS Science Citation Index Expanded, and
      HubMed) were searched. Abstracts that appeared to fulfill the initial selection
      criteria were selected, and the full-text original articles were retrieved and
      analyzed. Only articles that fulfilled the final selection criteria were finally
      considered. Their references were also hand-searched for possible missing
      articles from the database searches. RESULTS: Nine abstracts met the initial
      inclusion criteria and these articles were retrieved. From these, five were later
      rejected mostly because the sample dealt with growing subjects. Four articles
      remained and they showed that the upper and lower lips retracted and the
      nasolabial angle increased following premolar extraction. Upper lip retraction
      ranged from 2 mm to 3.2 mm, lower lip retraction ranged from 2 mm to 4.5 mm.
      CONCLUSIONS: The lip procumbency improves following the extraction of four
      premolars and this improvement is predictable. However, the changes are small and
      do not dramatically modify the profile. A "dished in" profile is not to be
      expected. Individual variation in response is large.

PMID- 19852664
TI  - Risk factors for mortality in patients with nosocomial Stenotrophomonas
      maltophilia pneumonia.
AB  - OBJECTIVE: The aim of this study was to determine potential risk factors for
      mortality in patients with nosocomial Stenotrophomonas maltophilia pneumonia.
      DESIGN: A retrospective, single-center, observational study. SETTING: A 2400-bed
      tertiary teaching hospital in southern Taiwan. PATIENTS AND METHODS: This
      retrospective study evaluated patients (age, at least 18 years) with nosocomial
      pneumonia (S. maltophilia isolated from respiratory culture) who were seen at
      Kaohsiung Chang Gung Memorial Hospital over a 3-year period. A total of 406
      patients (64% male, mean age +/- standard deviation, 69.6 +/- 14.93 years; mean
      duration of hospital +/- standard deviation, 57.5 +/- 39.47 days) were included.
      RESULTS: Most index isolates (53.9%) were from the first sample cultured.
      Polymicrobial isolates were cultured from samples from 177 (43.6%) of the 406
      study patients. The most common copathogen was Pseudomonas aeruginosa (53.11% of
      isolates). The all-cause hospital mortality rate was 42.6% (173 deaths among 406
      patients). Survivors had a shorter time from admission to a positive index
      culture result than did nonsurvivors (26.1 vs 31.7 days; P = .04). Mortality was
      significantly higher among patients with malignancy (adjusted odds ratio [AOR],
      2.48; 95% confidence interval [CI], 1.52-4.07; P < .001), renal disease (AOR,
      2.6; 95% CI, 1.51-4.47; P = .001), intensive care unit stay (AOR, 1.72; 95% CI,
      1.1-2.7; P = .018), and inadequate initial empirical antibiotic therapy (AOR,
      2.17; 95% CI, 1.4-3.38; P = .001). CONCLUSIONS: S. maltophilia pneumonia is
      associated with a high mortality rate and is commonly associated with concomitant
      polymicrobial colonization or infection. Underlying comorbidities and inadequate
      initial empirical antibiotic therapy substantially account for increased
      mortality rates.

PMID- 19852665
TI  - Should vascular surgery patients be screened preoperatively for methicillin
      resistant Staphylococcus aureus?
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) can cause severe
      infection in patients who are undergoing vascular surgical operations. Testing
      all vascular surgery patients preoperatively for MRSA and attempting to
      decolonize those who have positive results may be a strategy to prevent MRSA
      infection. The economic value of such a strategy has not yet been determined.
      METHODS: We developed a decision-analytic computer simulation model to determine
      the economic value of using such a strategy before all vascular surgical
      procedures from the societal and third-party payer perspectives at different MRSA
      prevalence and decolonization success rates. RESULTS: The model showed
      preoperative MRSA testing to be cost-effective (incremental cost-effectiveness
      ratio, <$50,000 per quality-adjusted life year) when the MRSA prevalence is > or
      = 0.01 and the decolonization success rate is > or = 0.25. In fact, this strategy
      was dominant (ie, less costly and more effective) at the following thresholds:
      MRSA prevalence > or = 0.01 and decolonization success rate > or = 0.5, and MRSA
      prevalence > or = 0.025 and decolonization success rate > or = 0.25. CONCLUSION:
      Testing and decolonizing patients for MRSA before vascular surgery may be a cost
      effective strategy over a wide range of MRSA prevalence and decolonization
      success rates.

PMID- 19852666
TI  - Antimicrobial stewardship programs in pediatrics.
AB  - OBJECTIVE: To describe the prevalence, characteristics, and barriers to
      implementation of antimicrobial stewardship programs (ASPs) in pediatrics. DESIGN
      AND PARTICIPANTS: In December 2008, we surveyed the pediatric members of the
      Emerging Infections Network, a network of infectious diseases consultants located
      throughout North America. Participants responded regarding whether their hospital
      had or planned to develop an ASP, its characteristics, barriers to improvement or
      implementation, and perceptions about antimicrobial resistance. RESULTS: Of 246
      pediatric infectious disease consultants surveyed, 147 (60%) responded. Forty
      five respondents (33%) reported having an ASP, and 25 (18%) were planning a
      program. The percentage of respondents from freestanding children's hospitals who
      were planning ASPs was higher than the percentage of respondents from other
      settings who were planning ASPs (P = .04). Most existing programs were developed
      before 2000 and had a limited number of full-time equivalent staff, and few
      programs used a prospective audit-and-feedback structure. Many programs were not
      monitoring important end points associated with ASPs, including cost and number
      of antibiotic-days. The major barriers to implementation of an ASP were lack of
      resources, including funding, time, and personnel, noted by more than 50% of
      respondents. Regardless of the presence of an ASP, respondents perceived
      antibiotic resistance as a more significant problem nationally than at their
      local hospital (P < .001). CONCLUSIONS: The prevalence of ASPs in pediatrics is
      limited, and opportunities exist to improve current programs.

PMID- 19852668
TI  - Natural control of HIV-1 replication and long-term nonprogression: overlapping
      but distinct phenotypes.

PMID- 19852667
TI  - Domain 3 of hepatitis C virus core protein is sufficient for intracellular lipid
      accumulation.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver disease worldwide,
      with steatosis, or "fatty liver," being a frequent histologic finding. In
      previous work, we identified sequence polymorphisms within domain 3 (d3) of
      genotype 3 HCV core protein that correlated with steatosis and in vitro lipid
      accumulation. In this study, we investigated the sufficiency of d3 to promote
      lipid accumulation, the role of HCV genotype in d3 lipid accumulation, and the
      subcellular distribution of d3. METHODS: Stable cell lines expressing green
      fluorescent protein (GFP) fusions with isolates of HCV genotype 3 core steatosis
      associated d3 (d3S), non-steatosis-associated d3 (d3NS), and genotype 1 d3 (d3G1)
      were analyzed by means of immunofluorescence, oil red O (ORO) staining, and
      triglyceride quantitation. RESULTS: Cells that expressed d3S had statistically
      significantly more ORO than did cells expressing d3NS or d3G1 (P=.02 and <.001,
      respectively), as well as higher triglyceride levels P =.03 and .003,
      respectively). Immunofluorescence analysis showed that d3 does not colocalize to
      lipid droplets but partially colocalizes to the Golgi apparatus. CONCLUSIONS: Our
      results suggest that HCV core d3 is sufficient to mediate the accumulation of
      lipid by means of a mechanism that is independent of domains 1 and 2. Our results
      also suggest that altered lipid trafficking may be involved.

PMID- 19852669
TI  - Clinical outcomes of elite controllers, viremic controllers, and long-term
      nonprogressors in the US Department of Defense HIV natural history study.
AB  - Durable control of human immunodeficiency virus (HIV) replication and lack of
      disease progression in the absence of antiretroviral therapy were studied in a
      military cohort of 4586 subjects. We examined groups of elite controllers (ie,
      subjects with plasma HIV RNA levels of <50 copies/mL; prevalence, 0.55% [95%
      confidence interval {CI}, 0.35%-0.80%]), viremic controllers (ie, subjects with
      plasma HIV RNA levels of 50-2000 copies/mL; prevalence, 3.34% [95% CI, 2.83%
      3.91%]), and subjects with a lack of disease progression (ie, long-term
      nonprogressors [LTNPs]) through 7 years of follow-up (LTNP7s; prevalence, 3.32%
      [95% CI, 2.70%-4.01%]) or 10 years of follow-up (LTNP10s; prevalence, 2.04% [95%
      CI, 1.52%-2.68%]). For elite and viremic controllers, spontaneous virologic
      control was established early and was typically observed when the initial viral
      load measurement was obtained within 1 year of estimated seroconversion. Elite
      controllers had favorable time to development of AIDS (P=.048), a CD4 cell count
      of 350 cells/microL (P= .009), and more-stable CD4 cell trends, compared with
      viremic controllers. LTNPs defined by 10-year versus 7-year criteria had a longer
      survival time (P=.001), even after adjustment for differing periods of
      invulnerability (P= .042). Definitions of controllers and LTNPs describe distinct
      populations whose differing clinical outcomes improve with the stringency of
      criteria, underscoring the need for comparability between study populations.

PMID- 19852670
TI  - Salmonella infection of gallbladder epithelial cells drives local inflammation
      and injury in a model of acute typhoid fever.
AB  - The gallbladder is often colonized by Salmonella during typhoid fever, yet little
      is known about bacterial pathogenesis in this organ. With use of a mouse model of
      acute typhoid fever, we demonstrate that Salmonella infect gallbladder epithelial
      cells in vivo. Bacteria in the gallbladder showed a unique behavior as they
      replicated within gallbladder epithelial cells and remained confined to those
      cells without translocating to the mucosa. Infected gallbladders showed
      histopathological damage characterized by destruction of the epithelium and
      massive infiltration of neutrophils, accompanied by a local increase of
      proinflammatory cytokines. Damage was determined by the ability of Salmonella to
      invade gallbladder epithelial cells and was independent of high numbers of
      replication-competent, although invasion-deficient, bacteria in the lumen. Our
      results establish gallbladder epithelial cells as a novel niche for in vivo
      replication of Salmonella and reveal the involvement of these cells in the
      pathogenesis of Salmonella in the gallbladder during the course of acute typhoid
      fever.

PMID- 19852672
TI  - Comment on 'Culture as an explanation in population health'.

PMID- 19852673
TI  - Body fat and skinfold thicknesses: a dimensional analytic approach.
AB  - BACKGROUND: Body fat may be estimated from skinfold thickness measurements
      (Skfs), but current prediction equations are dimensionally inconsistent and do
      not properly allow for the influence of body size on fat mass. AIM: To find a
      dimensionally correct formula relating fat content to Skfs and body size.
      SUBJECTS AND METHODS: 285 African children aged 9-11 years, with fat content
      measured by dual-energy X-ray absorptiometry, were studied. Because least-squares
      regression parameters can be a misleading guide to true functional relationships,
      the real data were compared with simulated data sets conforming to a
      dimensionally correct statistical model. RESULTS: The data are consistent with
      functional relationships such that fat mass is proportional to Skfxheight(2). The
      mean ratio (fat mass)/(Skfxheight(2)) is 6% higher in the girls than in the boys.
      DISCUSSION: Appropriately, Skfxheight(2) has the dimensions of fat mass/density.
      Height(2) has no obvious physical significance and a more meaningful expression
      might be 'heightxX', where X corresponds to some measure of body width or girth.
      CONCLUSION: In formulae for predicting fat mass, multiplying Skfs by height(2)
      gives better estimates, especially for the tallest and shortest individuals. Fat
      mass, rather than percentage body fat (%BF), is best taken as the variable
      initially predicted.

PMID- 19852674
TI  - The effect of socio-economic status and area of residence on household food
      variety in Morocco.
AB  - BACKGROUND: In Morocco, few studies have specifically addressed the association
      between food variety and household socio-economic status and area of residence.
      AIM: The study's objective was to obtain a qualitative description of food
      consumption in samples of Moroccan households and to examine the influence of
      socio-economic factors and area of residence on their food variety. SUBJECTS AND
      METHODS: A qualitative food frequency questionnaire was administered by
      adolescent school pupils in their own households between March 2005 and March
      2006 in 526 households in the regions of Marrakesh north of the High Atlas range
      and Ouarzazate to the south. We calculated the Food Variety Index (FVI) based on
      183 food items and compared scores for advantaged/disadvantaged and urban/rural
      households. RESULTS: Mean FVI scores for all individuals and total food groups
      differ significantly between the area of residence, urban and peri-urban
      Marrakesh and urban Ouarzazate having the highest scores. The mean total FVI
      scores, presented according to the household's socio-economic status from highest
      to lowest, are 123.8 +/- 17.1 for urban Marrakesh, 107.6 +/- 21.6 for urban
      Ouarzazate, 92.0 +/- 22.4 for rural Skoura, 110.5 +/- 21.5 for peri-urban
      Marrakesh and 89.9 +/- 10.8 for rural Iguerferouane (F-test = 26.7, p < 0.001).
      Advantaged households have significantly greater variety than disadvantaged
      households for all variables only in the two urban samples. In peri-urban
      Marrakesh and rural Skoura, there are no significant differences between
      advantaged and disadvantaged households. CONCLUSION: In our Moroccan sample, food
      variety is distributed according to two patterns: One based on area of residence,
      urban areas having greater variety than rural areas, and the other on socio
      economic factors, with advantaged households having higher FVI values but only in
      urban areas. The limited availability of certain foods and food preferences by
      the populations mean that not all households are able to diversify their diets.

PMID- 19852675
TI  - Growth status of indigenous school children 6-14 years in the Tarahumara Sierra,
      Northern Mexico, in 1990 and 2007.
AB  - AIMS: The study evaluated the growth status and secular change in body size of
      indigenous Tarahumara children in northern Mexico. METHODS: Heights and weights
      of Tarahumara children 6-14 years were measured in 1990 (n = 601) and 2007 (n =
      583); the BMI was calculated. International criteria defined weight status while
      United States reference data defined stunting. RESULTS: Estimated secular gains
      in height from 1990 to 2007 were greatest in 6-7 year-old boys and declined with
      age to a small, non-significant secular decline in boys 12-14 years. Among girls
      secular gains in height were similar at 6-7 and 8-9 years, largest at 10-11 years
      and small and non-significant at 12-14 years. Secular gains in weight were
      similar among 6-7 and 8-9 year-old boys and girls, were greater in girls than in
      boys at 10-11 years and showed a small, non-significant secular decline in boys
      and girls 12-14 years. Secular change in the BMI paralleled those for weight. The
      prevalence of stunting declined from 1990 to 2007 in both sexes and all age
      groups except 12-14 year youth. Overweight was more prevalent in girls than boys
      in both years and increased from 4% to 7% in boys and 9% to 13% in girls. Obesity
      was not common among boys and girls in each age group and in both years. Stunting
      and overweight/obesity were not related in either 1990 or 2007. CONCLUSION:
      Positive secular changes in growth status have occurred in Tarahumara children 6
      11 years in contrast to negligible changes among children 12-14 years. The
      results suggest recent improvements in health and nutrition sufficient to support
      a positive secular trend in younger children.

PMID- 19852676
TI  - Secular growth changes in stature and weight for Chinese Mongolian youth, 1964
      2005.
AB  - BACKGROUND: A secular growth trend has been demonstrated in China during the past
      half century. However, few studies have involved minority ethnicity. AIM: This
      study demonstrates secular changes in stature and weight for Chinese Mongolians
      from 1964 to 2005, and analyses the correlations with environmental factors,
      revealing inequalities within populations. SUBJECTS AND METHODS: Data were
      gathered from 7- to 18-year-old students in the Inner Mongolian Autonomous Region
      of China, both from local records in 1964 and from the 1985, 1991, 1995, 2000 and
      2005 cycles of the Chinese National Survey on Students' Constitution and Health.
      RESULTS: During the past 41 years, the average rates of stature increments for 7-
      to 17- year-olds are 1.9 and 2.0 cm per decade, of weight are 2.2 and 1.5 kg per
      decade and of BMI are 0.5 and 0.3 kg/m(2) per decade, for males and females,
      respectively. The overall increments of stature in 18-year-old males and females
      from 1985 to 2005 are 2.3 and 2.1 cm, respectively. The rate of change of stature
      is stronger in the first three decades, while that of weight and BMI are greater
      in the last decade. Evidence strongly suggests that changes may have occurred
      since the late 1970s. CONCLUSION: The positive growth changes of Chinese
      Mongolian people are closely related to urbanization, socio-economic progress and
      living improvements.

PMID- 19852677
TI  - Hypertension and its correlates in two communities of dissimilar genetic ancestry
      in Sikkim, India.
AB  - BACKGROUND: Hypertension has emerged as a major health risk among adults and the
      elderly in India. In spite of sharing similar physical and cultural environments,
      group level cultural variability and distinct genetic ancestry may result in
      differences in patterns of hypertension prevalence. AIM: The present study
      investigates the relationships between socio-economic, lifestyle and
      anthropometric variables and hypertension in two communities (Rai and Bhutia) of
      Sikkim. Both groups live in a similar ecological setting and are exposed to
      forces of modernization of almost equal magnitude. SUBJECTS AND METHODS: The
      study sample consists of 582 Rais and 315 Bhutias. Information on socio
      demographic characteristics, substance uses and other lifestyle variables were
      collected through relevant pre-tested questionnaires. Anthropometric measurements
      were taken following standard methods. Three consecutive blood pressure
      measurements were taken and averaged for analysis. RESULTS: The results of
      covariance analyses show that ethnicity is not a significant covariate of either
      systolic or diastolic blood pressure. Use of tobacco and alcohol consumption,
      level of education and activity patterns were found to be significant correlates
      of hypertension. The diagnostic ability of waist circumference is found to be
      better than body mass index for assessment of risk of hypertension among the
      present study populations. CONCLUSIONS: Lifestyle factors more than ethnicity and
      socio-economic factors contribute to the development of hypertension in these
      populations. Based on the results of this study, we would suggest that a
      sustainable increase in physical activity and reduction in alcohol consumption
      would be helpful in the proper management of hypertension for both groups.

PMID- 19852679
TI  - Human mitochondrial DNA variation in Southern Italy.
AB  - BACKGROUND: Since prehistoric times Southern Italy has been a cultural crossroads
      of the Mediterranean basin. Genetic data on the peoples of Basilicata and
      Calabria are scarce and, particularly, no records on mtDNA variability have been
      published. AIM: In this study mtDNA haplotypes of populations from Basilicata,
      Calabria and Sicily are compared with those of other Italian and Mediterranean
      populations, so as to investigate their genetic relationships. SUBJECTS AND
      METHODS: A total of 341 individuals was analysed for mtDNA in order to provide
      their classification into haplogroups. Multivariate analysis was used to compare
      the studied populations with other Mediterranean samples; median-joining network
      analysis was applied to observe the relationship between the major lineages of
      the Southern Italians. RESULTS: The haplogroup distribution in the Southern
      Italian samples falls within the typical pattern of mtDNA variability of Western
      Eurasia. The comparison with other Mediterranean countries showed a substantial
      homogeneity of the area, which is probably related to the historic contact
      through the Mediterranean Sea. CONCLUSION: The mtDNA analysis demonstrated that
      Southern Italy displays a typical pattern of Mediterranean basin variability,
      even though it appears plausible that Southern Italy was less affected by the
      effects of the Late Glacial Maximum, which reduced genetic diversity in Europe.

PMID- 19852680
TI  - Preclinical models for pulmonary drug delivery.
AB  - BACKGROUND: The lung comprises an interesting route of administration not only
      for topical drugs but also for systemically acting drugs. Over the last years,
      several models have been developed in order to study the efficacy and safety of
      pulmonary drug delivery. OBJECTIVE: This review describes relevant drug delivery
      models for preclinical evaluation of inhaled drug products. METHODS: Epithelial
      cell culture models, the isolated perfused lung and in vivo models are reviewed.
      The suitability and limitations of each method are discussed. This review is
      mostly based on publications from the last 10 years. RESULTS/CONCLUSION: Cell
      cultures are ideal models to compare transport rates of molecules and to study
      their mechanisms of transepithelial transport. Yet the most complete assessment
      of pulmonary drug delivery including delivery efficacy and safety remains
      provided by studies performed in vivo in animal models.

PMID- 19852681
TI  - Technology for improving the bioavailability of small molecules extracted from
      traditional Chinese medicines.
AB  - Evidence that small molecules extracted from traditional Chinese medicines (TCMs)
      have beneficial effects on health is increasingly being reported in the
      scientific literature and these compounds are now widely recognized as potential
      therapeutic drugs. There have been several detailed studies of the absorption,
      distribution, metabolism and excretion of these compounds in rats and humans.
      However, some active components have low bioavailability owing to their
      unsuitable physicochemical and biopharmaceutical characteristics, resulting in
      differences in vivo. The main problem in using natural products as a source of
      pharmaceutical lead compounds is the need to improve the bioavailability of these
      compounds. This review presents and discusses the current methods used for
      improvement and their impact on the bioavailability of some new pharmaceutical
      lead compounds from TCMs.

PMID- 19852682
TI  - The platelet protein kinase C substrate pleckstrin binds directly to SDPR
      protein.
AB  - Pleckstrin is a modular platelet protein consisting of N- and C-terminal
      pleckstrin homology (PH) domains, a central dishevelled egl10 and pleckstrin
      (DEP) domain and a phosphorylation region. Following agonist-induced platelet
      stimulation, dimeric pleckstrin translocates to the plasma membrane, is
      phosphorylated and then monomerizes. A recent study found that pleckstrin null
      platelets from a knockout mouse have a defect in granule secretion, actin
      polymerization and aggregation. However, the mechanism of pleckstrin signaling
      for this function is unknown. Our recent studies have led to the identification
      of a novel pleckstrin-binding protein, serum deprivation response protein (SDPR),
      by co-immunoprecipitation, GST-pulldowns and nanospray quadruple time of flight
      mass spectrometry. We show that this interaction occurs directly through N
      terminal sequences of pleckstrin. Both pleckstrin and SDPR are phosphorylated by
      protein kinase C (PKC), but the interaction between pleckstrin and SDPR was shown
      to be independent of PKC inhibition or activation. These results suggest that
      SDPR may facilitate the translocation of nonphosphorylated pleckstrin to the
      plasma membrane in conjunction with phosphoinositides that bind to the C-terminal
      PH domain. After binding of pleckstrin to the plasma membrane, its
      phosphorylation by PKC exerts downstream effects on platelet
      aggregation/secretion.

PMID- 19852683
TI  - Pre-analytical effects of pneumatic tube transport on impedance platelet
      aggregometry.
AB  - Point-of-care platelet monitoring is increasingly used in cardiac patients
      treated with antiplatelet agents. The validity of a new assay needs to be
      evaluated not only for reproducible data in clinical samples, but also for other
      pre-analytical conditions that may influence measurements. The aim of this study
      was to evaluate the influence of a pneumatic tube system (PTS) for specimen
      transport on impedance platelet aggregometry. We evaluated 50 consecutive
      patients scheduled for coronary artery bypass surgery under oral therapy with 100
      mg/d acetylsalicylic acid (aspirin). In each patient, three blood samples for
      platelet function analysis were taken before induction of anesthesia. The first
      sample was measured in the operating room (OR) area and designated as the
      reference value. The second sample was again measured by the same operator in the
      OR area using a random PTS transport. The third sample was sent to the central
      laboratory by PTS where it was measured by a local technician. Platelet function
      was assessed in whole blood by impedance aggregometry with a Multiplate analyzer
      using thrombin-related activation peptide (TRAP test) and arachidonic acid (ASPI
      test) (Dynabite GmbH, Munich, Germany). Mean +/- SD for TRAP test was 1009 +/-
      196 in the reference measurement. Bias +/- 95% limit of agreement between the
      reference measurement and a second measurement for TRAP test were 126 +/- 284 (n
      = 25) for untransported and 181 +/- 316 (n = 25) for PTS transported samples. In
      the reference measurements, 48/50 (96%) of TRAP values were within the normal
      range. After PTS transport, 35/50 (70%) of TRAP measurements in the central
      laboratory were within the normal range (p < 0.001). Mean +/- SD for ASPI test
      was 175 +/- 137. Bias +/- 95% limit of agreement for ASPI test were 12 +/- 109 (n
      = 25) for untransported and 68 +/- 250 (n = 25) for PTS transported samples. In
      the reference measurements, 7/50 (14%) ASPI values were above the cut-off level
      and defined as reduced aspirin responsiveness. After PTS transport, only 1/50
      (2%) of the patients showed reduced aspirin responsiveness in the central
      laboratory measurements (p = 0.031). In conclusion, PTS transport had a
      significant influence on platelet function testing by the Multiplate() analyzer.
      Significantly fewer test results indicated normal platelet function in TRAP test
      and reduced aspirin responsiveness in ASPI test after PTS transport. Therefore,
      clinical decisions regarding platelet function and aspirin responsiveness should
      not be based on blood specimens transported by a PTS system.

PMID- 19852684
TI  - Circadian variation of platelet function measured with the PFA-100.
AB  - The circadian rhythm plays an important role in the physiology and
      pathophysiology of the human being. Previous investigations revealed a circadian
      rhythm also in platelet function but these investigations have been limited to
      optical aggregometry with platelet-rich plasma and low shear stress. The aim of
      the present study was to further elucidate the impact of the circadian rhythm on
      platelet function using whole blood at high shear rates. Platelet function
      determined with the platelet function analyzer PFA-100 and concentration of
      fibrinogen and factor VIII activity were measured in healthy volunteers during
      day and night time, and even at shorter intervals (8:00, 12:00, 16:00, 20:00,
      22:00, 0:00, 2:00, 4:00, 6:00 h). The mean peak closure time of the
      collagen/epinephrine cartridge of the PFA-100 was maximal at 2:00 h (192.0 +/-
      57.4 s) and declined to the trough value at 8:00 h (140.1 +/- 33.4 s) (p =
      0.004). This was paralleled by data from the collagen/ADP cartridge (22:00 h:
      99.1 +/- 38.5 s/2:00 h: 81.3 +/- 16.7 s; p = 0.049). Concentration of fibrinogen
      and factor VIII activity were lowest during night time (22:00-4:00 h). These
      findings demonstrate a circadian rhythm in platelet function as measured with the
      PFA-100. The PFA-100 seems to be an appropriate tool to describe circadian
      alterations and is easier to use than optical aggregometry in analogous studies.

PMID- 19852685
TI  - Stroke and aspirin non-responder patients: relation with hypertension and
      platelet response to adenosine diphosphate.
AB  - Despite its widespread use, there are many concerns about the efficacy of aspirin
      in the secondary prevention of cardiovascular events after stroke, leading to the
      concept of aspirin non-response (ANR). Although the mechanisms of ANR remain
      uncertain, it is expected to be due to a combination of clinical, biological and
      genetic characteristics affecting platelet function. In this study, we
      investigated whether clinical and/or biological factors such as hypertension and
      platelet response to ADP could contribute to the ANR. As a secondary objective,
      we determine whether ANR and collagen/ADP closure time (CADP-CT) could be related
      to platelet glycoprotein single nucleotide polymorphisms (SNPs). One hundred
      patients on aspirin (160 mg/day) were enrolled. ANR was measured with a platelet
      function analyzer (PFA-100); genotyping of four SNPs (GP IIIa, GP Ia, P2Y12 and
      GP VI) was performed using a tetra-primer amplification refractory mutation
      system. Using a collagen/epinephrine-coated cartridge on the PFA-100, the
      prevalence of ANR was 15% (n = 15). In the ANR group, (i) CADP-CT was
      significantly shorter and (ii) hypertension was an independent clinical
      predictive factor of ANR (OR = 4.25; 95%CI: 1.06-17.11). No clear relation was
      found between CADT-CT and platelet gene polymorphism as well as ANR status and
      SNPs. In conclusion our study confirms the independent relationship between
      hypertension, platelet hypersensitivity to ADP and aspirin (160 mg/day) non
      response. The differential sensitivity to aspirin may have potential clinical
      implications, where adaptation of antiplatelet therapy is necessary according to
      a patient's clinical and genetic characteristics.

PMID- 19852686
TI  - Nitric oxide inhibits platelet adhesion to collagen through cGMP-dependent and
      independent mechanisms: the potential role for S-nitrosylation.
AB  - Nitric oxide (NO)-mediated inhibition of platelet function occurs primarily
      through elevations in cGMP, although cGMP-independent mechanisms such as S
      nitrosylation have been suggested as alternative NO-signaling pathways. In the
      present study we investigated the potential for S-nitrosylation to act as a NO
      mediated cGMP-independent signaling mechanism in platelets. The NO-donor, S
      nitrosoglutathione (GSNO), induced a concentration-dependent inhibition of
      platelet adhesion to immobilized collagen. In the presence of the soluble
      guanylyl cyclase inhibitor, ODQ, NO-mediated activation of the cGMP/protein
      kinase G signaling pathway was ablated. However, ODQ failed to completely abolish
      the inhibitory effect of NO on collagen-mediated adhesion, confirming that cGMP
      independent signaling events contribute to the regulation of platelet adhesion by
      NO. Biotin-switch analysis of platelets demonstrated the presence of several S
      nitrosylated proteins under basal conditions. Treatment of platelets with
      exogenous NO-donors, at concentrations that inhibited platelet adhesion,
      increased the number of S-nitrosylated bands and led to hyper-nitrosylation of
      basally S-nitrosylated proteins. The extent of S-nitrosylation in response to
      exogenous NO was unaffected by platelet activation. Importantly, platelet
      activation in the absence of exogenous NO failed to increase S-nitrosylation
      beyond basal levels, indicating that platelet-derived NO was unable to induce
      this type of protein modification. Our data demonstrate that S-nitrosylation of
      platelet proteins in response to exogenous NO may act as a potentially important
      cGMP-independent signaling mechanism for controlling platelet adhesion.

PMID- 19852687
TI  - Effects of garcinol and guttiferone K isolated from Garcinia cambogia on
      oxidative/nitrative modifications in blood platelets and plasma.
AB  - The effects of garcinol and guttiferone K, two polyisoprenylated benzophenones
      occurring a food plant called Garcinia cambogia, on oxidative/nitrative protein
      damage (determined by parameters such as levels of protein carbonyl groups and
      nitrotyrosine residues) in human blood platelets and plasma after treatment with
      peroxynitrite (ONOO(-)) were studied in vitro. We also investigated the effects
      of garcinol and guttiferone K on lipid peroxidation in blood platelets and plasma
      induced by ONOO(-) (100 microM). Exposure of blood platelets or plasma to
      peroxynitrite (100 microM) resulted in an increased level of carbonyl groups and
      nitrotyrosine residues in proteins, and an increase of lipid peroxidation
      measured by the level of thiobarbituric acid reactive species (TBARS). In the
      presence of garcinol and guttiferone K (0.1-25 microg/ml), a distinct reduction
      in the formation of carbonyl groups in plasma and platelet proteins together with
      the decrease of TBARS caused by 100 microM peroxynitrite, was observed. However,
      garcinol and guttiferone K did not inhibit plasma and platelet protein nitration
      induced by peroxynitrite. Polyisoprenylated benzophenones present in human diet
      such as garcinol or guttiferone K in vitro have protective effects against lipid
      and protein oxidation and may have some promising effects in vivo because they
      are good antioxidants in the tested models in vitro. Garcinol and guttiferone K
      can be also useful as protecting factors against diseases associated with
      oxidative stress.

PMID- 19852688
TI  - Elevated platelet-monocyte complexes in patients with psoriatic arthritis.
AB  - We evaluated platelet and endothelial activation parameters in psoriatic
      arthritis (PsA), a disease reported to be associated with the development of
      endothelial dysfunction and increased atherosclerotic complications. Twenty
      patients with PsA, eight psoriasis and 20 healthy controls were included into the
      study. The patients' clinical features and acute phase parameters were assessed.
      In all patients and controls, platelet-monocyte complexes (PMC), platelet
      neutrophil complexes (PNC), and basal and ADP-stimulated P-selectin expression
      were determined with flow cytometry; soluble E-selectin (sE-selectin) and soluble
      CD40L (sCD40L) were determined with ELISA. Patterns of joint involvement and
      degrees of skin involvement in PsA patients were assessed. PMC in PsA patients
      were significantly higher than in the control group (p = 0.02). PNC were not
      significantly different among the three groups (p values > 0.05). sE-selectin
      levels in both PsA and psoriasis groups were significantly higher than in healthy
      controls (p values, respectively, <0.001 and 0.023). Basal and ADP-stimulated
      CD62P expression and sCD40L level were similar in all groups (p values > 0.05).
      Polyarticular PsA patients had significantly higher sCD40L than oligoarticular
      plus spondylitic PsA groups (p = 0.04). sCD40L level was higher in active PsA
      group than in inactive PsA group (p = 0.03). Groups with limited and extensive
      skin involvement did not differ significantly in the evaluated parameters. C
      reactive protein (CRP) level in PsA patients correlated with sCD40L (r = 0.69, p
      = 0.012), basal CD62P expression (r = 0.89, p < 0.001) and ADP-stimulated CD62P
      expression (r = 0.73, p = 0.001). Endothelial activation might be have a role in
      the pathogenesis of both psoriasis and PsA. Among parameters of platelet
      activation, only PMC might play a role in the pathogenesis of PsA.

PMID- 19852689
TI  - Clinical management of clopidogrel inefficiency by point of care platelet
      function testing and individual adjustment of anti-platelet therapy--initial
      experiences.
AB  - Insufficient inhibition of ADP dependent platelet aggregation by clopidogrel is
      associated with an increased risk for adverse coronary events, such as stent
      thrombosis, after percutaneous coronary intervention. Here, we describe an
      approach to the clinical management of patients with insufficient inhibition of
      ADP dependent platelet aggregation by clopidogrel involving dose adjustment or
      switching of the thienoyridine. We put special emphasize on a patient who
      experienced recurrent acute myocardial infarction due to stent thrombosis
      associated with severe clopidogrel non response following elective coronary drug
      eluting stent implantation. In this patient, an inadequate clopidogrel effect at
      maintenance doses was confirmed by repeated platelet function assessment with a
      multiple electrode impedance point of care platelet function test. Subsequent
      dose adjustments still did not result in sufficient inhibition of ADP dependent
      platelet aggregation. Only after switching to the then shortly available new
      thienopyridine prasugrel could a sufficient platelet inhibition be obtained.
      However, our data from further patients show that although this may overcome
      inadequate clopidogrel efficiency in many cases, even under prasugrel suboptimal
      platelet inhibition may occur.

PMID- 19852690
TI  - Capture of platelets to the endothelium of the femoral vein is mediated by CD62P
      and CD162.
AB  - Platelets contribute to blood coagulation at sites of vascular injury and to the
      recruitment of leukocytes at sites of inflammation. Under pathological
      conditions, platelets are involved in numerous diseases and clinical
      complications, such as deep venous thrombosis, embolism and atherosclerosis. But
      so far, little is known about the mechanisms of inflammation in large veins and
      the role of platelets in inflamed large veins. For this purpose, we investigated
      primary and secondary interactions between platelets, leukocytes and endothelial
      cells in the femoral vein in vivo with special regard to the role of CD62P (P
      selectin) and CD162 (PSGL-1). Mice were challenged with lipopolysaccharide
      (LPS)/D-galactosamine (D-gal) and either CD162 or CD62P was blocked by
      intravenous administration of a corresponding antibody at the time point of LPS/D
      gal injection. Four hours after LPS/gal injection, intravital fluorescence
      microscopy of the femoral vein was performed and primary and secondary platelet
      leukocyte-endothelial cell-interactions were visualized after in vivo platelet
      and leukocyte staining with rhodamine 6G. Analysis of intravital fluorescence
      microscopy revealed that LPS/D-gal caused a strong inflammatory reaction of the
      venous endothelium with significant induction of platelet and leukocyte
      tethering, rolling and adhesion. Secondary interactions of platelets to adherent
      or rolling platelets or leukocytes were also increased after LPS/D-gal-injection.
      Immunoneutralization of either CD162 or CD62P significantly decreased platelet
      primary and secondary capture as well as leukocyte rolling and adhesion. CD162
      and CD62P play a central role in mediating inflammatory primary and secondary
      interactions of platelets and leukocytes to the endothelium in inflamed large
      veins in vivo. Thus, blocking CD162 or CD62P might be an attractive tool for
      preventing platelet and leukocyte-driven venous diseases.

PMID- 19852691
TI  - Nephropathy in type 1 diabetes is associated with increased circulating activated
      platelets and platelet hyperreactivity.
AB  - Patients with diabetes mellitus (DM) have increased platelet activation compared
      to non-diabetic controls. Platelet hyperreactivity has been associated with
      adverse cardiovascular outcomes in Type 2 DM, and with diabetic nephropathy. We
      investigated the relationship between platelet activation and nephropathy in Type
      1 DM. Patients with Type 1 DM and diabetic nephropathy (n = 35), age- and sex
      matched Type 1 DM patients with persistent normoalbuminuria (n = 51), and healthy
      age- and sex-matched controls (n = 30) were studied. Platelet surface P-selectin,
      platelet surface activated GPIIb/IIIa, monocyte-platelet aggregates (MPAs) and
      neutrophil-platelet aggregates (NPAs) were measured by whole blood flow cytometry
      as markers of platelet activation. Platelet reactivity was assessed in response
      to exogenously added ADP and thrombin receptor activating peptide (TRAP).
      Platelet surface P-selectin (basal and in response to 0.5 or 20 microM ADP) was
      higher in nephropathy patients compared with normoalbuminuric patients (P =
      0.027), and non-diabetic controls (P = 0.0057). NPAs were higher in nephropathy
      patients compared to normoalbuminuric patients (P = 0.0088). MPAs were higher in
      nephropathy patients compared to non-diabetic controls (P = 0.0075). There were
      no differences between groups in activated GPIIb/IIIa or in response to TRAP at
      any end-point. More patients with nephropathy received aspirin (71.4%) compared
      to normoalbuminuric patients (27.4%) (P < 0.0001). Type 1 diabetic nephropathy,
      as compared with normoalbuminuria, is associated with circulating activated
      platelets and platelet hyperreactivity to ADP, despite the confounding variable
      of more nephropathy patients receiving aspirin. This platelet activation is
      likely to contribute to the known increased risk of cardiovascular events in
      patients with diabetic nephropathy.

PMID- 19852692
TI  - Thrombopoiesis in small for gestational age newborns.
AB  - Thrombocytopenia in small for gestational age (SGA) newborns may be due to
      placental vascular pathology, fetal consumptive coagulopathy and platelet
      destruction, local imbalance of thromboxane A2 causing placental vasoconstriction
      and platelet aggregation. Thrombopoiesis in SGA newborns is poorly recognized. In
      61 SGA newborns we evaluated thrombocytopoiesis in relation to gender and the
      rate maturity expressed as <5th percentile and <10th percentile. Female newborns
      demonstrated higher thrombopoietin (TPO) level at 92.06 pg/ml than male newborns
      at 79.81 pg/ml. Newborns less developed <5th percentile, showed increased TPO
      level of 92.0 pg/ml in comparison to <10th percentile of 78.0 pg/ml. This
      observation is more pronounced in female newborns. Contrary to our expectations
      we did not find any statistically significant differences in the percentage of
      reticulated platelets (PLRET) and platelets count in relation to gender and <5th
      percentile or <10th percentile. We can postulate intrauterine hypoxia is
      responsible for the increase of erythropoietin and impairment of thrombopoiesis
      in SGA newborns.

PMID- 19852693
TI  - Efficacy and safety of anti-D for treatment of adults with immune
      thrombocytopenia.
AB  - This study was planned to assess the response of anti-D in patients with immune
      thrombocytopenia (ITP). Twenty adults (8 males: 12 females) with a median age
      33.5 years (19-59 years) were included. Nine patients had newly-diagnosed ITP, 6
      had persistent ITP and 5 had chronic ITP. The overall response rate was 65%.
      Patients with newly diagnosed ITP showed response rates of 77% (7/9), persistent
      ITP had response rates 50% (3/6) and patients with chronic ITP had response rates
      of 60% (3/5). The median time to response was 3 days (1-11 days). There was no
      correlation of response with age, sex, severity of bleeding, presenting platelet
      counts, ABO blood group or prior steroid or IVIG response.

PMID- 19852694
TI  - Effects of heat on camel platelet structure and function--a comparative study
      with humans.

PMID- 19852697
TI  - Long-term treatment of patients with Alzheimer's disease in primary and secondary
      care: results from an international survey.
AB  - OBJECTIVE: The International Outcomes Survey in Dementia (IOSID) was initiated to
      observe the effects of current standard of care for Alzheimer's disease (AD) on
      patient outcomes and caregiver burden in a real-life setting. RESEARCH DESIGN AND
      METHODS: This 2-year, international, prospective, longitudinal and observational
      cohort survey involved patients with mild-to-moderate AD (Mini-Mental State
      Examination [MMSE] scores of 10-26 points) living in an ordinary household at
      baseline. There was no intervention with regard to patient management. Primary
      informal caregivers were also included in the survey. MAIN OUTCOME MEASURES:
      Patient parameters assessed included the MMSE, Disability Assessment for Dementia
      (DAD), Neuropsychiatric Inventory (NPI), and Clinical Global Impression (CGI).
      Caregiver burden was evaluated with the Zarit Burden Interview and caregiver
      distress was assessed as part of the NPI. Adverse events (AEs) were monitored.
      RESULTS: Of 2288 patients recruited, 1382 (60.4%) completed the survey. At
      baseline, the majority (79.3%) of patients were receiving treatment with
      acetylcholinesterase inhibitors (AChEIs) or/and memantine. MMSE, DAD, NPI and CGI
      scores all showed that patients experienced deterioration of AD symptoms during
      the survey. MMSE scores declined less steeply than might have been expected based
      on historical data. Scores on the four outcome scales were significantly
      correlated at all time points. Mean caregivers' feeling of strain and caregiver
      distress increased during the survey. AEs occurring in more than 2% of patients
      were nausea (3.0%), injury (2.6%), fall (2.4%), depression (2.2%) and urinary
      tract infection (2.2%). CONCLUSIONS: Community patients with AD experience
      progressive and interconnected decline in cognition, behaviour and functioning
      over time, placing increased burden on caregivers. However, improved care in
      recent years, including AChEI use, might be reflected in slower rates of patient
      decline than were evident in the past. Overall, relatively low rates of AEs were
      apparent during the survey. Limitations of this survey included a smaller than
      anticipated number of recruited patients confounding the possibility of
      performing comprehensive subgroup analyses, and the lack of randomisation
      inherent in the survey methodology.

PMID- 19852698
TI  - Hydrogen sulfide increases glutathione production and suppresses oxidative stress
      in mitochondria.
AB  - Hydrogen sulfide (H(2)S) is a synaptic modulator as well as a neuroprotectant in
      the brain. We recently showed that H(2)S protects neurons from oxidative stress
      by increasing the levels of glutathione (GSH), a major cellular antioxidant, by
      more than twice that of a control through enhancing the cystine transport. Here
      we show that H(2)S enhances the transport of cysteine to increase GSH production
      more than cystine transport and to redistribute the localization of GSH to
      mitochondria. The efficiency of GSH production enhanced by H(2)S is even greater
      by fourfold under oxidative stress by glutamate. H(2)S reinstated GSH levels in
      the fetal brain decreased by ischemia/reperfusion in utero. In addition, Neuro2a
      cells expressing a mitochondrial H(2)S-producing enzyme, 3-mercaptopyruvate
      sulfurtransferase (3MST), along with cysteine aminotransferase (CAT), showed
      significant resistance to oxidative stress. The present study shows that H(2)S
      protects cells from oxidative stress by two mechanisms. It enhances the
      production of GSH by enhancing cystine/cysteine transporters and redistributes
      GSH to mitochondria. H(2)S produced in mitochondria also may directly suppress
      oxidative stress. It provides a new mechanism of neuroprotection from oxidative
      stress by H(2)S.

PMID- 19852699
TI  - Incidence and economic burden of suspected adverse events and adverse event
      monitoring during AF therapy.
AB  - OBJECTIVE: Rhythm- and rate-control therapies are an essential part of atrial
      fibrillation (AF) management; however, the use of existing agents is often
      limited by the occurrence of adverse events. The aim of this study was to
      evaluate suspected adverse events and adverse event monitoring, and associated
      medical costs, in patients receiving AF rhythm-control and/or rate-control
      therapy. RESEARCH DESIGN AND METHODS: This retrospective cohort study used claims
      data from the Integrated Healthcare Information Systems National Managed Care
      Benchmark Database from 2002-2006. Patients hospitalized for AF (primary
      diagnosis), and who had at least 365 days' enrollment before and after the
      initial (index) AF hospitalization, were included in the analysis. Suspected AF
      therapy-related adverse events and function tests for adverse event monitoring
      were identified according to pre-specified diagnosis codes/procedures, and
      examined over the 12 months following discharge from the index hospitalization.
      Events/function tests had to have occurred within 90 days of a claim for AF
      therapy to be considered a suspected adverse event/adverse event monitoring.
      RESULTS: Of 4174 AF patients meeting the study criteria, 3323 received AF drugs;
      428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765
      combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients
      had a suspected adverse event and/or function test for adverse event monitoring
      (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined
      rhythm/rate-control). Suspected cardiovascular adverse events were the most
      common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and
      endocrine events (5.9%). Overall, suspected adverse events/function tests were
      associated with mean annual per-patient costs of $3089 ($1750 with rhythm
      control, $2041 with rate control, and $6755 with combined rhythm/rate-control).
      LIMITATIONS: As a retrospective analysis, the study is subject to potential
      selection bias, while its reliance on diagnostic codes for identification of AF
      and suspected adverse events is a source of potential investigator error. A
      direct cause-effect relationship between suspected adverse events/function tests
      and AF therapy cannot be confirmed based on the claims data available.
      CONCLUSIONS: The incidence of suspected adverse events and adverse event
      monitoring during AF rhythm-control and/or rate-control therapy is high. Costs
      associated with adverse events and adverse event monitoring are likely to add
      considerably to the overall burden of AF management.

PMID- 19852700
TI  - Development of a participatory process to address fragmented application of
      outcome measurement for rehabilitation in community settings.
AB  - PURPOSE: Outcome measurement is an integral part of delivering rehabilitation
      services in community settings. However, measurement is of little value if
      instruments are chosen ad hoc and are not administered consistently. The purpose
      of this study was to develop and test a participatory process of outcome measure
      selection which would engender consistent use of robust and appropriate
      instruments. METHOD: The ICF provided the conceptual framework for a systematic
      review of the literature for relevant outcome measures. A summary of the critical
      appraisal of the clinimetric properties of the identified instruments was
      created. The summaries were reviewed and vetted by stakeholders including
      clinicians, researchers, and managers/policy makers. RESULTS: From the 300
      identified and appraised measures, 28 were chosen and made available in a
      Compendium of Clinical Measures for Community Rehabilitation. The Compendium
      contains three core measures to be used routinely with all rehabilitation clients
      and a further 25 that cover particular discipline and client needs. This resource
      is now available to all clinicians working in the participating rehabilitation
      services. CONCLUSION: A participatory process combining rigorous review of the
      literature, expert opinion, and clinician feedback is recommended in the
      selection and implementation of outcome measures in rehabilitation settings in
      the community.

PMID- 19852701
TI  - Disability and rehabilitation: do we ever think about needed dental care? A case
      study: the USA.
AB  - PURPOSE: To foster an awareness of the need for oral health care as a component
      of a programme for rehabilitation of individuals with disabilities. METHOD: A
      case study of the USA is used to illustrate the evolving community residential
      settings for individuals with disabilities and the resulting complexities in the
      delivery of health services. Examples of oral health conditions frequently
      present in individuals with disabilities are provided. RESULTS: National and
      local reports indicate that barriers exist in the delivery of oral health
      services for individuals with intellectual/developmental and later life
      disabilities. CONCLUSION: Oral health care is a component of rehabilitation, as
      long as attendant pain erodes energy and aspirations of individuals with
      disabilities. Dental practitioners face many of the same complex difficulties
      encountered by other health practitioners in the provision of services for
      individuals with disabilities. The need is for the practitioners in the many
      health fields to play an important role in developing an awareness of, and
      referrals for, necessary oral health care.

PMID- 19852702
TI  - The experiences of adults with complex communication needs who volunteer.
AB  - PURPOSE: The aim of this study was to explore the experiences of adults with
      complex communication needs (CCN) who engage in volunteering. METHOD: In-depth
      interviews were conducted with 24 adults with CCN who had worked as volunteers.
      Interview transcripts were analysed according to grounded theory methodology.
      RESULTS: 'Control' emerged as the most important factor determining the nature of
      the participants' volunteering experiences. Two key strategies for enhancing
      control were the provision of augmentative and alternative communication (AAC)
      systems and appropriate support to volunteer. A theoretical model to account for
      the experiences of volunteers with CCN is presented. CONCLUSIONS: Adults with CCN
      who want to volunteer must have access to an effective communication system and
      appropriate support if they are to volunteer successfully for the benefit of
      themselves and others.

PMID- 19852703
TI  - Recovery from acute injury: clinical, methodological and philosophical
      considerations.
AB  - BACKGROUND: The foundational basis for rehabilitation of musculoskeletal injury
      as a profession rests upon the ability of an organism to recover from a deviation
      in homeostasis, and the clinician's ability to influence that process. Much work
      has been done in an effort to describe and predict recovery from acute injury, in
      particular soft tissue injuries of the spine (whiplash and low back pain). Recent
      reviews have identified inconsistencies in the criteria for identifying recovery
      in this literature that hamper attempts at knowledge translation. PURPOSE: This
      article is intended to stimulate discussion around a new, standardised and
      acceptable set of criteria for discriminating between the injured individual who
      reaches a satisfying end to the experience of injury and the individual who does
      not reach that end. CONCLUSIONS: Self-discrepancy theory and self-determination
      theory are used to frame the discussion. It is hoped that the introduction of a
      new paradigm will lead to the development of more standardised, acceptable and
      useful outcomes, and will facilitate data synthesis from studies on prognosis and
      intervention for acute musculoskeletal injury.

PMID- 19852704
TI  - Perceptions of informal care givers: health and support services provided to
      people with multiple sclerosis.
AB  - PURPOSE: About 30% of people with multiple sclerosis (MS) need some form of home
      care assistance, with 80% of that assistance provided by informal or unpaid care
      givers. This study focuses on the care givers to 530 more disabled people with
      MS, with the objective to learn more about informal care giving to people with
      greater dependency and need for assistance. METHOD: The data presented in this
      study were collected in a national survey of 530 informal care givers to people
      with MS who have greater levels of physical dependency. RESULTS: About 70% of
      informal care givers responded that assisting the person with MS perform daily
      activities or personal care took up the largest amount of their care giving time.
      Care givers also reported a range of home and community-based services that would
      make care giving easier or improve the care provided. However, informal care
      givers generally reported low satisfaction with health insurance coverage of
      these services, especially coverage by health maintenance organizations and other
      managed care plans. CONCLUSIONS: Lack of health insurance coverage of needed home
      and community-based services can reduce the quality of informal care provided, as
      well as increase the burden of informal care giving.

PMID- 19852705
TI  - WHODAS II - Practical and theoretical issues.

PMID- 19852706
TI  - The effect of physiotherapy on sit-to-stand movements in a child with spastic
      diplegia.
AB  - PURPOSE: The purpose of this study was to assess sit-to-stand (STS) movements of
      a child with cerebral palsy before and after physiotherapy (PT), based on
      objective kinematic data. METHODS: A child with cerebral spastic diplegia, aged 4
      years and 6 months, and had no prior surgery, was the subject. In order to assess
      the STS movements before and after PT, a motion analysis system was used. STS
      movements data before and after PT which included the total duration of STS
      movement and angular movement of each joint were collected and compared. RESULTS:
      The total duration of STS movement was 3.06 s before PT and 2.44 s after PT. As
      for angular movement before PT, knee, hip joint, and trunk were flexed strongly
      just after ankle joint was in plantarflexion, in shifting the center of mass
      forward. In contrast, these flexion patterns were less noticeable after PT. In
      addition, standing postures showed marked improvement. Range of motion of ankle
      dorsiflexion was -25 degrees before PT; after PT, it was 6 degrees. CONCLUSION:
      These findings lead us to conclude that the effect of PT on STS movement before
      and after PT showed objective kinematic data.

PMID- 19852707
TI  - Implementing the ICF in a psychiatric rehabilitation setting for people with
      serious mental illness in the Lombardy region of Italy.
AB  - PURPOSE: We describe issues encountered in implementing the International
      Classification of Functioning, Disability, and Health (ICF) in a comprehensive
      psychiatric rehabilitation settings for people with Serious Mental Illness (SMI),
      with the goal of facilitating other implementation projects and stimulating
      international discussion. METHODS: In 2006, the Hospital Mellino Mellini
      Department of Mental Health undertook a 2-year evaluation of the applicability of
      the ICF to its community-based program for people with SMI, in collaboration with
      the Neurological Institute Carlo Besta Foundation. An ICF-based assessment of
      functional status was administered at intake, 3 months, and at 6 months, using an
      extended checklist of ICF codes determined to reflect the most important aspects
      of functioning among the SMI client population. All project focused on three
      important aspects of participation of these persons: housing, working, and
      socialization. RESULTS: Issues encountered during the project related to: (1) the
      identification of a relevant code set for the population; (2) difficulty in
      administering the checklist as a primary functional status measure; (3) whose
      perspective would be followed in rating functional status; (4) how to
      conceptualize the ICF Capacity qualifier; and (5) the need for teamwork and
      culture change for successful ICF implementation. CONCLUSIONS: On the basis of
      this experience and input from an international workshop convened by the
      Department, the project team concluded that the ICF is a helpful conceptual frame
      for functional status among people with SMI, promotes a common language and
      integrated treatment model, supports the development of individual rehabilitation
      plans, and can be used to improve services for this population.

PMID- 19852708
TI  - Detection of warning surfaces in pedestrian environments: the importance for
      blind people of kerbs, depth, and structure of tactile surfaces.
AB  - PURPOSE: The overall purpose was to study whether and how persons with blindness
      detect warning surfaces with a long white cane in a real pedestrian environment
      after following a natural guidance surface to the warning surfaces. Of particular
      interest was the importance of kerb, depth, and structure of the warning
      surfaces. METHOD: A concurrently mixed methods approach, with a combination of
      observation using a structured form together with 'think aloud' and a structured
      interview, was used. It was done with well-defined samples and study sites in an
      inter-disciplinary research context. RESULTS: The results show that the most
      important design characteristic for detection of the warning surfaces with a
      white cane is the structure of the surface, while the depth of the surface and
      availability of a kerb do not have any impact on the detection. A precondition
      was that there is a distinct natural guidance surface leading up to the warning
      surface. CONCLUSIONS: The probability among pedestrians with blindness to detect
      a tactile surface is not higher if the design solution has a kerb. This study
      also confirms the complexity of being a blind pedestrian in the traffic
      environment. The results can be used for evidence-based physical planning. The
      study also has implications for development of more efficient vision
      rehabilitation.

PMID- 19852709
TI  - Physical-activity coaching and health status in rheumatoid arthritis: a person
      oriented approach.
AB  - PURPOSE: No interventions to promote physical activity can succeed for all
      participants. Insights into the specific characteristics of those who do succeed
      are needed. One aim was to investigate whether a selection of correlates of
      general health perception creates cluster typologies in individuals with
      rheumatoid arthritis (RA). Another was to evaluate whether magnitude of change in
      health status differs between clusters after a 1-year coaching intervention
      targeting health-enhancing physical activity. METHOD: Two hundred and twenty
      eight patients (74% women, mean age 56 years, disease duration 1 year) with RA,
      from 10 rheumatology clinics in Sweden, participated. The patients were assigned
      at random to intervention or control. The intervention group underwent 1 year of
      coaching to adopt health-enhancing physical activity (moderately intensive, 30
      min/day, > 4 days/week). The cluster analysis included five correlates of general
      health perception: disease activity; pain; timed standing; activity limitation;
      and self-reported physical activity. The primary outcome of the coaching
      intervention was self-reported health status. RESULTS: One-hundred and forty-six
      patients were eligible for inclusion in the cluster analysis. The eight clusters
      identified both at baseline and post interventions were operationalized according
      to the number of cluster variables affected: less (LE) affected or more (MO)
      affected, respectively. Clusters with LE affected variables had significantly
      better general health perception at baseline than those with MO affected
      variables. Further, coached individuals in MO affected clusters significantly
      improved self-reported health status compared both to those coached in LE
      affected clusters and to those in MO affected clusters in the control group.
      CONCLUSION: This person-based approach contributed more than did the results in a
      previous randomized controlled trial to the understanding of which patients
      benefit most from the present physical-activity coaching intervention. The
      intervention may thus be most beneficial for individuals more severely affected
      by their disease at baseline.

PMID- 19852710
TI  - Quality of life: an important outcome measure in a trial of very early
      mobilisation after stroke.
AB  - Purpose. Commencing an early and active mobilisation programme in the acute
      stages of stroke may have important physical and psychological benefits that
      might improve long-term quality of life. We hypothesised that patients who
      received very early mobilisation (VEM) would experience better quality of life
      than those receiving standard care (SC). Methods. The study was a Phase II single
      blind randomised controlled trial: VEM patients received earlier (within 24 h of
      stroke onset) and more intensive physical therapy than SC patients for the first
      14 days (or until discharge). Quality of life was measured using the Assessment
      of Quality of Life (AQoL) questionnaire, administered face-to-face by a blinded
      assessor at 12 months post-stroke. Results. Seventy-one individuals with stroke
      (VEM 38, SC 33) were recruited. At follow-up, the median overall AQoL score was
      higher in VEM patients (0.32) than SC patients (0.24). This group difference was
      not significant (p = 0.17), but it was significant at the 75th percentile (p =
      0.003) in favour of VEM. VEM patients also reported higher quality of life than
      SC patients in the physical function related 'Independent Living' domain of the
      AQoL (p = 0.03 adjusted for age; p = 0.04 adjusted for stroke severity).
      Conclusions. VEM may help improve long-term quality of life after stroke,
      particularly in relation to functional independence, but this requires further
      examination.

PMID- 19852711
TI  - Mapping an obesity clinical evaluation protocol to the International
      Classification of Functioning, Disability and Health.
AB  - PURPOSE: To evaluate a multidisciplinary clinical protocol for obesity treatment
      by mapping it against the International Classification of Functioning, Disability
      and Health (ICF) and to determine the areas, defined by the ICF, in which no
      standardized assessment tools are available. METHOD: Assessment instruments used
      by a multidisciplinary team were linked to ICF categories and compared with a
      list of ICF categories composed by the ICF checklist and the comprehensive ICF
      core-set for obesity. Other relevant ICF categories were added, and not relevant
      ones were deleted when appropriate. RESULTS: Five ICF categories were deleted and
      11 were added, and 166 ICF categories were linked to assessment tools and to semi
      structured interviews. The majority were linked to assessment tools, but within
      the domain of the environmental factors all ICF categories were mapped using semi
      structured interviews. CONCLUSIONS: Our results show that an extended list of ICF
      categories is adequate to cover a wide spectrum of clinical and functional
      information, and it could be employed to describe, disability profiles of obese
      patients, to develop preventive measures and to identify what factors in the
      environment need to be changed to improve rehabilitation's outcomes.

PMID- 19852712
TI  - Pain and fatigue consistency in adults with cerebral palsy.
AB  - PURPOSE: To examine the consistency of pain and fatigue and describe pain
      interference with daily activities in ambulatory (AMB) and non-ambulatory (non
      AMB) adults with cerebral palsy (CP) over a 3-month period. METHOD: A repeated
      measures design with 26 participants (12 AMB, 14 non-AMB) acting as their own
      controls. Pain and fatigue data were collected once per month for three
      consecutive months using the FACES pain scale and PedsQL Multidimensional Fatigue
      Scale. Pain interference with daily life was assessed using the Pain Disability
      Index (PDI). RESULTS: No significant differences were found in maximum pain
      intensity. AMB reported significantly fewer pain sites in the whole body during
      month 1 than non-AMB. Fatigue was consistent across months; however, AMB reported
      significantly more General fatigue. Across groups, significant correlations were
      found between PDI and General, Resting, and Overall fatigue. Non-AMB exhibited
      significant correlations between total number of pain sites and General and
      Cognitive fatigue, as well as PDI and Overall fatigue. For the AMB group, PDI and
      total number of pain sites were significantly correlated. CONCLUSIONS: Pain and
      fatigue consistently and significantly affect adults with CP. Both factors impact
      the ability of adults, who have CP, to participate in daily life.

PMID- 19852713
TI  - Goal-directed functional therapy: a longitudinal study on gross motor function in
      children with cerebral palsy.
AB  - PURPOSE: To investigate gross motor function and goal attainment in children with
      cerebral palsy before, during and after goal-directed functional therapy (GDT),
      to evaluate body functions, and explore relationships. METHOD: Prospective
      longitudinal intervention study. Twenty-two children, uni- or bilateral CP, 1-6
      years (mean: 46 months SD: 16 months), classified in GMFCS and MACS level I-IV
      participated. Outcome measures were Gross Motor Function Measure (GMFM-66),
      performed at seven occasions, Goal Attainment Scale, assessments of passive range
      of motion, spasticity and selective motor control (SMC). Baseline, the GDT
      intervention and the follow-up period were 12 weeks each. RESULTS: Improvements
      were demonstrated in GMFM-66 during the intervention (mean difference: 5.07, CI:
      3.8-6.4, p < 0.001). The baseline and follow-up assessments were stable.
      Evaluations of ankle dorsiflexion displayed small improvement (mean difference: 9
      degrees , CI: 5-13, p < 0.001). Estimations of spasticity and SMC did not
      demonstrate significant changes. Goal attainment to the expected level or higher
      was achieved in 93/110 goals and further improved at the long-term follow-up
      (103/110). CONCLUSION: Gross motor function improved during GDT, and was
      maintained 12 weeks later. The goals were reached to a high extent, and the
      children gradually progressed towards their goals after the end of the
      intervention. The therapy did not induce any deterioration of body functions.

PMID- 19852714
TI  - Oral hygiene in scleroderma: The effectiveness of a multi-disciplinary
      intervention program.
AB  - PURPOSE: To investigate whether oral hygiene improves after persons with
      scleroderma received structured oral hygiene instructions and facial and hand
      exercises. METHODS: Seventeen persons with scleroderma received a baseline dental
      evaluation including an examination for decayed or missing teeth, calculus, sites
      that bleed upon probing, measures of oral aperture, and the Patient Hygiene
      Performance Index. Upper extremity functioning including strength, joint motion,
      and dexterity were also measured. Participants received a structured home program
      consisting of patient education on brushing and flossing techniques, hand and
      facial exercises, adapted dental appliances, and a 6-month supply of dental
      products. RESULTS: At the end of the 6-month intervention, there was a
      significant decrease (improvement) in mean PHP scores and a significant decrease
      in the number of teeth that bled on probing and with subgingival calculus. There
      were no differences in any of the upper extremity measures or oral aperture.
      Correlations between the upper extremity and oral measures showed associations
      between oral aperture and two of the dexterity measures and number of teeth with
      caries. CONCLUSION: These findings suggest that oral exercises and education
      regarding proper dental care may be useful in managing oral hygiene in persons
      with scleroderma.

PMID- 19852715
TI  - Evaluating rehabilitation outcomes from the client's perspective by identifying
      the gap between current and preferred movement ability.
AB  - PURPOSE: Examine the theoretical construct of a gap between people's perceived
      current and preferred movement abilities and its potential for evaluating
      rehabilitation outcomes against clients' desired goals. METHOD: A cross-section
      of 311 community-dwelling adults completed a 24-item movement ability measure
      (MAM) and a visual analog movement scale. In a nonrandomized pre-post design, two
      subsets of that population completed the measures again after 2 weeks: 35 clients
      undergoing outpatient physical therapy and 34 in a comparison group who were not
      undergoing physical therapy. Scores on the MAM were analyzed using item response
      theory methods. RESULTS: The gap between current and preferred ability in the 311
      adults represented one level difference on average out of six designated movement
      levels on both measures. Clients about to undergo physical therapy had gaps
      approximately twice the size of gaps in the 34-person comparison group on both
      measures (P < 0.001). Both the MAM and the movement scale showed a significantly
      narrower gap after 2 weeks for the group in physical therapy (P < 0.001) but no
      change for the comparison group. CONCLUSIONS: Assessing gaps between client
      perceived current and preferred movement ability following intervention may help
      in the evaluation of rehabilitation outcomes from the client's perspective.

PMID- 19852716
TI  - Discharge planning for patients receiving rehabilitation after hip fracture: a
      qualitative analysis of physiotherapists' perceptions.
AB  - PURPOSE: To explore the perceptions of clinicians about walking requirements and
      discharge criteria for patients being discharged home in the community from
      rehabilitation after hip fracture. METHODS: Twelve experienced clinicians (all
      females) (mean experience in rehabilitation 13 years) were interviewed using an
      in-depth semi-structured format. The recorded interviews were transcribed and
      coded independently by two researchers. From these codes themes were developed.
      RESULTS: For discharge planning, all clinicians considered personal/psychosocial
      factors such as patient goals and social support. Almost all clinicians
      considered that the performance factor of safe and independent ambulation was
      important to consider when planning the patient's discharge, but did not set
      specific distances or speeds. Clinicians expected that pain, a lack of
      confidence, and walking outdoors would affect the mobility at home but these
      factors were considered little in discharge planning. CONCLUSIONS: In planning
      discharge after rehabilitation for hip fracture, clinicians place more emphasis
      on the individual needs and goals of the patient than on specifying objective
      performance criteria that must be met. The expectation that lack of confidence
      could be a problem after returning home suggests that this factor could be
      considered more in discharge planning.

PMID- 19852717
TI  - 'They don't know how to defend themselves': talk about disability and HIV risk in
      South Africa.
AB  - PURPOSE: Disabled people in South Africa have been included, for the first time,
      in policy documents on HIV prevention. However, little is known about how persons
      with disabilities in South Africa may be at risk, or not. For policy to be
      implemented in effective practice, we need to know what the risk issues are for
      disabled people in South Africa. METHODS: This study draws on qualitative
      findings from a survey and interview study exploring organisational responses to
      the HIV epidemic for disabled people. Qualitative data were analysed using
      thematic and discourse analysis. RESULTS: An analysis of comments made about risk
      factors for HIV, identified sexual abuse as a key risk. Furthermore, findings
      suggest that disability stigma may be a key factor on increasing disabled
      people's vulnerability in engaging in unsafe sex. CONCLUSION: The findings
      provide much needed exploratory findings, in an area in which little is known;
      useful for considering issues for HIV prevention. However, caution needs to be
      taken that these findings are not the perspectives of disabled people themselves,
      and may reproduce accepted discursive truths.

PMID- 19852718
TI  - Evolution of sodium glucose co-transporter 2 inhibitors as anti-diabetic agents.
AB  - BACKGROUND: A critical factor for maintenance of glucose balance is the renal
      recovery of glucose from the glomerular filtrate mediated primarily by sodium
      glucose co-transporter 2 (SGLT2). This capacity can be modulated by SGLT2
      inhibitors thereby providing a unique insulin independent method of treatment of
      diabetes. OBJECTIVE/METHOD: A discussion of the evolution of SGLT inhibitors as
      inferred from patents published from 2005 to 2009 is prefaced by a brief review
      of the role of SGLT in glucose transport and the clinical findings illustrating
      the therapeutic potential of SGLT inhibitors as anti-diabetic agents. These
      compounds comprise O, C and N-glycosides generated by attachment of an
      appropriate lipophilic aglycone component to a suitable glucose analogue.
      CONCLUSION: The realization that the in vivo potency of O-glucosides was markedly
      less than that of C-glucosides necessitated a shift in medicinal chemistry focus
      of the pharmaceutical companies pursuing SGLT2 inhibitors. Particular emphasis is
      placed on the strategy that each used to circumvent the constraints imposed by
      prior art while utilizing a common pharmacophore. The role of SGLT2 inhibitors
      for treatment of diabetes will be established by the outcome of the five
      compounds in advanced clinical trials.

PMID- 19852719
TI  - Aptamers: from bench side research towards patented molecules with therapeutic
      applications.
AB  - BACKGROUND: RNA and DNA aptamers recognize their targets with high specificity
      and affinity. These aptamers can be developed against almost any target protein
      through iterative cycles of in vitro screening of a combinatorial oligonucleotide
      library for target binding. Aptamer sequences from the final pool of in vitro
      selection are screened for pharmacological activity and possible medical
      applications. METHODS: Chemical modifications and improvements of the
      identification of aptamer selection procedures made aptamers rival antibodies in
      diagnostic and therapeutic applications. This article reviews recent literature
      and patents and discusses the properties of aptamers as high-affinity and
      specificity target binders as well as their stability in biological fluids that
      turns them into therapeutic agents. CONCLUSION: The development of aptamers into
      compounds with therapeutic and diagnostic compounds has resulted in patents
      protecting the sequences and the use of these oligonucleotides. Several of these
      patented aptamers are currently being tested in Phase I or II clinical trials.
      Moreover, an anti-VEGF aptamer has already been approved by the FDA for treatment
      of age-related macular degeneration in humans.

PMID- 19852721
TI  - New porcine model for training for laparoscopic ureteral reimplantation with horn
      of uterus to mimic enlarged ureter.
AB  - PURPOSE: To develop a new porcine model with horn of the uterus to mimic an
      enlarged ureter for training for laparoscopic ureteral reimplantation (LUR) and
      to evaluate its feasibility. MATERIALS AND METHODS: Ten female pigs were used in
      the training. The pig was placed to a dorsal position after an anesthetic was
      administered. The horn of the uterus near the bladder was dissected, then
      spatulated and trimmed to replace the enlarged ureter. LUR was performed
      according to standard operation steps. Four trainees completed the LUR procedure
      based on a mentor-trainee model to guarantee the success of the procedure and the
      quality of the anastomoses. The learning curve of operative time was analyzed.
      The anastomotic stoma was cut off postoperatively and checked extracorporeally.
      After the course, questionnaire surveys were sent to the trainees to investigate
      satisfaction of the training and assess the impact of the training on their
      learning of "real" LUR in future practice. RESULTS: This model reproduced the key
      technique steps of LUR. Four LUR procedures were performed on each pig. The
      operative time declined from 170.0 +/- 10.3 minutes to 90.3 +/- 3.7 minutes (P <
      0.01) after the trainees had performed 10 LURs. There was proper stitching in
      each "ureterovesical" anastomosis. At the end of training, all trainees could
      accomplish a LUR procedure skillfully on the model; they were satisfied after the
      course and thought the training was helpful to future practice of LUR.
      CONCLUSION: The new model was feasible and cost-effective for training in the
      basic skills of laparoscopic ureteral reconstruction procedures.

PMID- 19852723
TI  - Changing trends in the use of ureteroscopic instruments from 1996 to 2008.
AB  - PURPOSE: Despite ongoing advances in the field of endourology, there are few
      reports describing specific changes adopted by urologists that have come as a
      result. We investigated the progression of single surgeon's clinical practice
      over a 12-year period, noting differences in ureteroscopes, ancillary equipment,
      and indications for surgery over that time. METHODS: The records of 1181 patients
      undergoing ureteroscopy by a single surgeon were reviewed. Consecutive patients
      from the years 1996 (n = 200), 1998 (n = 179), 2000 (n = 198), 2002 (n = 127),
      2004 (n = 137), 2006 (n = 200), and 2008 (n = 140) were included in the study.
      Patients remained grouped by the year of their procedure for comparison. Compared
      variables included the indication for surgery, type of anesthesia, method of
      ureteral dilation and stabilization, specific ureteroscopes used, type and number
      of working instruments employed, and the method of postprocedure ureteral
      drainage. RESULTS: A change favoring smaller, more flexible ureteroscopes was
      seen. An increase in the percentage of surgeries performed for upper tract tumors
      paralleled decreasing trends in urolithiasis and ureteropelvic junction
      obstruction surgery. A divergence in the devices used for calculi and upper tract
      tumors was seen. CONCLUSIONS: Over the past 12 years, technological advancements
      in the field of endourologic surgery have resulted in shifting clinical practice
      for endourologists, with trends favoring smaller, actively flexible
      ureteroscopes, intrarenal surgery, and nitinol basket use.

PMID- 19852722
TI  - Holmium laser enucleation of the prostate for prostates larger than 175 grams.
AB  - BACKGROUND AND PURPOSE: Open simple prostatectomy has been considered the
      treatment of choice for symptomatic benign prostatic hyperplasia (BPH) of large
      prostates because traditional endoscopic techniques have not proven either
      effective or feasible. We present our experience with holmium laser enucleation
      of the prostate (HoLEP) for glands >175 cc. METHODS: An Institutional Review
      Board approved prospective database has been maintained since January 1999 for
      all HoLEP procedures. The database was reviewed retrospectively for patients who
      underwent HoLEP for BPH with a preoperative transrectal ultrasonography (TRUS)
      volume of >175 cc. RESULTS: From January 1999 to November 2008, we identified 57
      patients with a mean pretreatment TRUS volume of 217.8 cc (range 175-391 cc).
      Preoperative retention was present in 30 patients. Preoperative mean prostate
      specific antigen level was 14.6 ng/mL, mean American Urological Association (AUA)
      symptom index was 19.0, and mean peak flow (Qmax) was 8.2 mL/sec. Mean hospital
      stay was 26 hours, and postoperative catheterization was 18.5 hours (range 6-96
      hrs). All patients were able to void after catheter removal. Mean enucleated
      tissue weight was 176.4 g (range 48-532.2 g). At 6-month follow-up, AUA symptom
      index was 6.5, mean PSA level was 0.78 ng/mL, and Qmax was 18.5. During the
      follow-up period, no patient needed catheterization or had persistent
      incontinence. CONCLUSIONS: Even in the large prostate gland, HoLEP provides a
      satisfactory outcome with low morbidity. HoLEP is the only endoscopic technique
      that allows for tissue removal comparable to that of open prostatectomy for such
      patients.

PMID- 19852724
TI  - Epithelial-mesenchymal transition in tumor metastasis: a method to the madness.

PMID- 19852725
TI  - Epithelial-mesenchymal transition in mouse mammary tumorigenesis.
AB  - Epithelial-mesenchymal transition tumorigenesis in the mouse has been described
      for over 100 years using various terms and with little comprehension of the
      underlying mechanisms. Recently, epithelial-mesenchymal transition tumors have
      been recognized in mammary glands of genetically engineered mice. This review
      provides a historical perspective and the current observations in the context of
      some of the key molecular biology. The biology of mouse mammary epithelial
      mesenchymal transition tumorigenesis is discussed with comparisons to human
      breast cancer.

PMID- 19852726
TI  - Epithelial-mesenchymal transition in development and cancer.
AB  - The epithelial-mesenchymal transition (EMT) is a critical developmental process
      from the earliest events of embryogenesis to later morphogenesis and organ
      formation. EMT contributes to the complex architecture of the embryo by
      permitting the progression of embryogenesis from a simple single-cell layer
      epithelium to a complex three-dimensional organism composed of both epithelial
      and mesenchymal cells. However, in most tissues EMT is a developmentally
      restricted process and fully differentiated epithelia typically maintain their
      epithelial phenotype. Recently, elements of EMT, specifically the loss of
      epithelial markers and the gain of mesenchymal markers, have been observed in
      pathological states, including epithelial cancers. Analysis of the molecular
      mechanisms of this oncogenic epithelial plasticity have implicated the
      inappropriate expression and activation of developmental EMT programs, suggesting
      that cancer cells may reinstitute properties of developmental EMT including
      enhanced migration and invasion. Thus, in the context of cancer, an EMT-like
      process may permit dissemination of tumor cells from the primary tumor into the
      surrounding stroma, setting the stage for metastatic spread. Consistent with this
      hypothesis, activation of these developmental EMT programs in human cancer
      correlates with advanced disease and poor prognosis. This review will focus on
      the current knowledge regarding developmental EMT pathways that have been
      implicated in cancer progression.

PMID- 19852729
TI  - Bevacizumab in brain tumors: ready for primetime?

PMID- 19852728
TI  - Epithelial-mesenchymal transition in hepatocellular carcinoma.
AB  - The transition of epithelial cells to a mesenchymal phenotype is of paramount
      relevance for embryonic development and adult wound healing. During the past
      decade, the epithelial-mesenchymal transition (EMT) has been increasingly
      recognized to occur during the progression of various carcinomas such as
      hepatocellular carcinoma (HCC). Here, we focus on EMT in both experimental liver
      models and human HCC, emphasizing the underlying molecular mechanisms which show
      partial recurrence of embryonic programs such as TGF-beta and Wnt/ beta-catenin
      signaling, including collaboration with hepatitis viruses. We further discuss the
      differentiation repertoire of malignant hepatocytes with respect to the potential
      acquisition of stemness, and the involvement of the mesenchymal to epithelial
      transition, the reversal of EMT, in cancer dissemination and metastatic
      colonization. The strong evidence for EMT in HCC patients demands novel
      strategies in pathological assessments and therapeutic concepts to efficiently
      combat HCC progression.

PMID- 19852730
TI  - Down's syndrome: protection against cancer and the therapeutic potential of
      DSCR1.

PMID- 19852731
TI  - Nanomolecular targeting of dendritic cells for ovarian cancer therapy.

PMID- 19852727
TI  - Mechanisms of the epithelial-mesenchymal transition by TGF-beta.
AB  - The formation of epithelial cell barriers results from the defined spatiotemporal
      differentiation of stem cells into a specialized and polarized epithelium, a
      process termed mesenchymal-epithelial transition. The reverse process, epithelial
      mesenchymal transition (EMT), is a metastable process that enables polarized
      epithelial cells to acquire a motile fibroblastoid phenotype. Physiological EMT
      also plays an essential role in promoting tissue healing, remodeling or repair in
      response to a variety of pathological insults. On the other hand,
      pathophysiological EMT is a critical step in mediating the acquisition of
      metastatic phenotypes by localized carcinomas. Although metastasis clearly is the
      most lethal aspect of cancer, our knowledge of the molecular events that govern
      its development, including those underlying EMT, remain relatively undefined.
      Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that
      oversees and directs all aspects of cell development, differentiation and
      homeostasis, as well as suppresses their uncontrolled proliferation and
      transformation. Quite dichotomously, tumorigenesis subverts the tumor suppressing
      function of TGF-beta, and in doing so, converts TGF-beta to a tumor promoter that
      stimulates pathophysiological EMT and metastasis. It therefore stands to reason
      that determining how TGF-beta induces EMT in developing neoplasms will enable
      science and medicine to produce novel pharmacological agents capable of
      preventing its ability to do so, thereby improving the clinical course of cancer
      patients. Here we review the cellular, molecular and microenvironmental
      mechanisms used by TGF-beta to mediate its stimulation of EMT in normal and
      malignant cells.

PMID- 19852733
TI  - Clofarabine for the treatment of adult acute myeloid leukemia.
AB  - Clofarabine, a next-generation deoxyadenosine analog, has demonstrated
      significant activity in patients with acute myeloid leukemia (AML). The single
      agent activity compares favorably with that demonstrated by the current standard
      antileukemia agents. Clofarabine has been safely and effectively combined with
      other agents and will probably become an integral part of induction and/or
      consolidation regimens in AML. Current studies are underway to better define the
      role of clofarabine in younger and elderly patients with AML, and also explore
      development strategies for an oral formulation.

PMID- 19852734
TI  - Nonsteroidal selective androgen receptor modulator Ostarine in cancer cachexia.
AB  - Cancer cachexia is a complex syndrome, affecting up to 60% of the approximately
      1.4 million patients diagnosed with cancer each year in the USA. This condition
      is characterized by progressive deterioration of a patient's nutritional status,
      weight loss, anorexia, diminished quality of life and increased mortality and
      morbidity. Current therapy with progestational, anti-inflammatory and anabolic
      agents is often ineffective and has a large number of undesirable effects. The
      newly developed nonsteroidal selective androgen receptor modulator Ostarine has
      demonstrated promising results in Phase I and II clinical trials, increasing
      total lean body mass, enhancing functional performance and decreasing total
      tissue percent fat. This selective androgen receptor modulator may have the
      ability to perform as a potent anabolic agent with minimal side effects on other
      organs (prostate and hair follicles), thus presenting a new strategy in managing
      cancer cachexia. However, more extensive data is required before its efficacy is
      confirmed.

PMID- 19852735
TI  - Oral oncology: imagine the future.

PMID- 19852736
TI  - Is BRAF mutation screening useful for preoperative risk stratification in
      papillary thyroid cancer?

PMID- 19852737
TI  - Characterization and functional role of the stroma compartment in prostate
      tumors.

PMID- 19852738
TI  - Wharton's jelly stromal cells as potential delivery vehicles for cancer
      therapeutics.
AB  - There is now compelling evidence that stem cells can be used as gene therapy
      delivery cells. Stem cells isolated from the Wharton's jelly of the umbilical
      cord (termed Wharton's jelly stromal cells) can be harvested noninvasively in
      large numbers and have been shown to traffic to tumors but do not form tumors
      themselves. WJS cells have low immunogenicity and they have also been engineered
      to secrete a cytokine, shown to home locally into the tumors in mice and with
      subsequent tumor attenuation. Naive rat and human Wharton's jelly stromal cells
      that are not engineered to secrete an exogenous protein also exert a potent
      anticancer effect in preclinical models.

PMID- 19852739
TI  - DNA methylation as a biomarker in breast cancer.
AB  - In cancer, epigenetic changes such as covalent addition of methyl groups to the
      genomic DNA itself are more prominent than genetic changes. Cytosine-phosphate
      guanosine (CpG) methylation negatively affects gene transcription of an adjacent
      gene. It is thought that DNA methylation significantly contributes to all
      hallmarks of cancer. Next to being a potential therapy target, DNA methylation is
      an emerging field of biomarkers. Technically, DNA provides a stable and robust
      analyte that is particularly suitable for clinical applications. Moreover, there
      are numerous potential human DNA sources that could facilitate integration of
      methylation tests in clinical practice. In breast cancer, DNA methylation has
      shown promise as a potential biomarker for early detection, therapy monitoring,
      assessment of prognosis or prediction of therapy response. In particular, paired
      like homeodomain transcription factor 2 (PITX2) DNA methylation has been
      validated using a robust assay for paraffin-embedded tissue for clinically
      relevant outcome prediction in early breast cancer patients treated by adjuvant
      tamoxifen therapy.

PMID- 19852740
TI  - Dietary patterns, risk and prognosis of breast cancer.
AB  - Survival in women diagnosed with early-stage, invasive breast cancer has improved
      dramatically in the past 10-15 years. This is largely due to the use of
      pharmacological therapies targeting a reduction in estrogen action and exposure.
      Women diagnosed with breast cancer often alter their eating behavior towards
      healthier food choices in an attempt to improve their survival and their overall
      health and well being. Mounting interest in the role of diet to modify breast
      cancer survival and/or comorbidity and mortality has led researchers to evaluate
      the effects of differential dietary patterns on this disease. Current findings
      suggest a possible, but inconsistent, benefit of a prudent, vegetable-rich, low
      fat/high-vegetable eating pattern on disease-free survival, but the results to
      date are limited by strong treatment effectiveness and low overall recurrence
      rates. It is more likely this prudent eating pattern will improve non-breast
      cancer mortality (e.g., cardiovascular disease) compared with a Western dietary
      pattern. Efforts to educate women diagnosed with breast cancer to consume a diet
      lower in total and saturated fat, higher in vegetables and fiber, and which
      results in mild to modest weight loss among overweight/obese women is sensible in
      light of the high survivability of breast cancer and need to direct attention to
      comorbidities that likely increase as a consequence of treatment and treatment
      related weight gain and sedentary behavior. Additional research is needed to
      address the importance of diet in the breast cancer patient, particularly in
      relation to the effect of select dietary patterns on factors that influence
      individual recurrence risk (e.g., hormone levels, drug metabolism and oxidative
      stress), as well as factors that influence non-breast cancer morbidity risk and
      causes of death in the survivor population.

PMID- 19852741
TI  - Molecular pathology of mixed-lineage leukemia.
AB  - Genomic rearrangements of the locus 11q23 are frequently observed in aggressive
      acute leukemias with poor prognosis. These chromosomal aberrations fuse the mixed
      lineage leukemia (MLL) gene to one of more than 50 partners. The resulting mixed
      lineage leukemia fusions often code for chimeric transcriptional activators,
      which are able to transform normal hematopoietic cells through the deregulation
      of leukemogenic target genes. This review provides a concise overview about the
      known functions encoded in MLL and the respective fusion partners. Additionally,
      the roles of some target genes, as well as co-factors of mixed-lineage leukemia
      fusion proteins, are described with an emphasis on recent advances potentially
      uncovering novel therapeutic targets.

PMID- 19852742
TI  - Diagnostic markers and prognostic factors in thyroid cancer.
AB  - There has been considerable progress identifying biomarkers in thyroid tumors
      that improve the accuracy of fine-needle aspiration biopsy and also help predict
      tumor aggressiveness or behavior. In this review we address both the clinical
      potential of molecular biomarkers and their usefulness, based on the most recent
      literature. We describe the current best clinical staging systems and the common
      somatic mutations in thyroid cancer. The BRAF mutation is the most common
      mutation in papillary thyroid cancer and has recently been reported to be
      associated with disease aggressiveness; it is also an independent predictor of
      tumor behavior. Combined testing of RET/PTC, NTRK, RAS and PAX8-PPARgamma, which
      are mutually exclusive mutations, helps improve the accuracy of fine-needle
      aspiration biopsy. Gene-expression profiling studies have identified a variety of
      potential molecular markers to help distinguish benign from malignant thyroid
      neoplasms. Expression analysis of differentially expressed microRNAs also appears
      to be a promising diagnostic approach for distinguishing benign from malignant
      thyroid neoplasm. It is especially useful for indeterminate nodules by fine
      needle aspiration biopsy.

PMID- 19852743
TI  - Preoperative staging of rectal cancer.
AB  - Preoperative staging is now an essential factor in the multidisciplinary
      management of rectal cancer because tumor stage is the strongest predictive
      factor for recurrence. Preoperative staging of rectal cancer can be divided into
      either local or distant staging. Local staging incorporates the assessment of
      mural wall invasion, circumferential resection margin involvement, as well as the
      nodal status for metastasis. Distant staging assesses for evidence of metastatic
      disease. The aim of this review is to consider the indications and limitations of
      the current preoperative imaging modalities for rectal cancer staging including
      clinical examination, endorectal ultrasound, magnetic resonance imaging, computed
      tomography and positron emission tomography-computed tomography, with respect to
      local and distant disease.

PMID- 19852745
TI  - International competition on mass spectrometry proteomic diagnosis.
AB  - This editorial describes a special issue of Statistical Applications in Genetics
      and Molecular Biology that presents a full report on an international competition
      on mass spectrometry proteomic diagnosis, recently organised at the Leiden
      University Medical Centre in The Netherlands.

PMID- 19852746
TI  - Rheumatoid arthritis and systemic lupus erythematosus as immune complex diseases.
AB  - Rheumatoid factors are 9s IgM autoantibodies directed against the hinge regions
      of 7s IgG's that have been changed consequent to their encounter with a foreign
      antigen, such as those produced by oral bacteria. Occasionally self-aggregating
      7s IgG's serve this function. When these complexes are taken up by phagocytes in
      the joint, they form the "RA cell," a cell analogous to the LE cell of Hargraves.
      The circulating complexes, which activate complement cascades in the joint, are
      not specific for RA, being found in other rheumatic and autoimmune diseases as
      well as having a low prevalence in the normal population. Recently, other
      antigens resulting in autoimmune complex formation with greater specificity for
      RA have been described. These antibodies, known as anti-cyclic citrullinated
      peptide (anti-CCP) antibodies recognize citrullinated protein residues, which are
      present as antigenic determinants in patients with RA. This is in contrast to
      systemic lupus erythematosus (SLE), another autoimmune disease characterized by
      immune complexes in the systemic circulation. In the case of SLE, 7s IgG's
      directed against several nuclear antigens localize mainly in the kidneys and
      blood vessels. They also produce cerebral and pulmonary disease by activating
      complement systemically. Genetic defects in the complement cascade associated
      with SLE result in inadequate clearance of immune complexes as well as apoptotic
      blebs containing autoantigens.

PMID- 19852747
TI  - Can RAPID3, an index without formal joint counts or laboratory tests, serve to
      guide rheumatologists in tight control of rheumatoid arthritis in usual clinical
      care?
AB  - Tight control of rheumatoid arthritis (RA) may be guided by RAPID3 (routine
      assessment of patient index data), an index without formal joint counts or
      laboratory tests, which can be scored on a multidimensional health assessment
      questionnaire (MDHAQ) in 5 seconds, compared to 42 seconds to score a standard
      HAQ, 90 seconds to perform a 28-joint count, 114 seconds to score a disease
      activity score 28 (DAS28), and 106 seconds to score a clinical disease activity
      index (CDAI). RAPID3 scores are correlated significantly with DAS28 and CDAI (rho
      > 0.65, p < 0.001), and distinguish active from control treatment similarly to
      DAS28 and CDAI in clinical trials of methotrexate, lefunomide, adalimumab,
      abatacept, certolizumab, and infiximab. RAPID3 scores can be used to classify
      patient disease activity status as high (> 12), moderate (6.1-12), low (3.1-6),
      and remission (<or= 3), analogous to activity categories of DAS28 and CDAI. In
      clinical care settings, 78% to 84% of patients who met the criteria for moderate
      high activity status of greater than 3.2 for DAS28 and greater than 10 for CDAI
      had RAPID3 scores greater than 6, while 68% to 77% who met low activity-remission
      criteria of a DAS less than or equal to 3.2 and a CDAI of less than or equal to
      10 also had RAPID3 scores that were less than or equal to 6. The most effective
      strategy to collect MDHAQ-RAPID3 data is for the receptionist to ask each patient
      to complete a questionnaire upon registration at each visit, prior to seeing the
      physician in the infrastructure of clinical care. Clinical judgment ultimately
      enters into all clinical decisions, but judgment is enhanced considerably by
      quantitative data provided by the MDHAQ and RAPID3 to supplement nonquantitative
      impressions. RAPID3 provides a feasible, informative quantitative index for busy
      clinical settings.

PMID- 19852748
TI  - Clinical trials for lupus--are we there yet?

PMID- 19852749
TI  - Updates on lupus and pregnancy.
AB  - This review focuses on events subsequent to planning a pregnancy and addresses
      three components of concern for women with systemic lupus erythematosus:
      maternal, placental, and fetal. Flare rates are generally low for patients who
      are clinically stable at conception. For patients who have never had renal
      disease, there is no frm evidence that they will develop active renal disease
      simply due to being pregnant. For patients who begin pregnancy with an abnormal
      creatinine (> 2 mg/dl is ill advised), risks include hypertension, preeclampsia,
      high rate of fetal loss, and possible further deterioration of renal function.
      Discontinuation of angiotensin converting enzyme inhibitors, angiotensin receptor
      blockers, and mycophenalate is mandatory. Elevated levels of sVEGF-1 may be a
      harbinger of preeclampsia. For patients with anti-phospholipid antibodies
      detected in the frst trimester of pregnancy, the lupus anticoagulant per se may
      be the strongest predictor of pregnancy complications. For women with anti-SSA/Ro
      antibodies the risk of having a child with congenital heart block is 2% which
      rises to a recurrence rate of 18%. Information on current approaches to
      prevention and treatment of heart complications of neonatal lupus is provided.

PMID- 19852750
TI  - Demystifying neuropsychiatric lupus--is it possible?
AB  - The occurrence of nervous system events in patients with systemic lupus
      erythematosus (SLE) remains a diagnostic and therapeutic challenge due to the
      diversity of clinical manifestations, the correction attribution of events to SLE
      or other causes, and the lack of clinical trial data to facilitate the selection
      of treatment options. Over the past decade the classifcation and attribution of
      neuropsychiatric (NP) events has received more rigorous attention and new
      insights into the pathogenetic mechanisms have emerged through neuroimaging
      studies and elucidation of autoimmune and infammatory mechanisms. Although much
      work remains to be done on this complex and fascinating aspect of lupus, there is
      an emerging consensus on the pathogenesis and treatment of NP-SLE.

PMID- 19852751
TI  - Low bone mass--assessing absolute fracture risk and the need to treat younger
      postmenopausal women.
AB  - The need to initiate treatment for a postmenopausal woman with a low bone mass
      should be based on that individual's fracture risk over a fnite period of time.
      Fracture assessment tools, such as the recently introduced FRAX(TM) model, allows
      the clinician to estimate an individual's absolute fracture risk over the next
      decade of their life. Such estimates are particularly useful for younger
      postmenopausal females with bone density values in the osteopenic range. Fracture
      risk increases with age and is inversely related to bone mineral density values.
      A history of previous fracture after the age of 45 and within 10 years of
      assessment increases subsequent fracture risk.

PMID- 19852752
TI  - Hyperuricemia, gout, and cardiovascular disease--an important "muddle".
AB  - Multiple epidemiologic studies confrm an association between hyperuricemia and
      cardiovascular disease (CVD), but it remains uncertain whether hyperuricemia is
      an independent or dependent risk factor for CVD. The question is particularly
      complex since patients with gout frequently have multiple comorbid conditions and
      adjusting for these conditions tends to reduce the strength of hyperuricemia as a
      risk factor. In this article, we review the data supporting a possible
      independent role for hyperuricemia in CVD. A close reading of the literature
      suggests that hyperuricemia may be both an independent and dependent risk factor,
      and is more likely to act as an independent risk factor in blacks, women, and
      patients with high risk for CVD. We also review the literature that suggests that
      hyperuricemia may directly contribute to the development of a number of comorbid
      conditions that in turn contribute to CVD risk (e.g., hypertension, glucose
      intolerance, renal insuffciency, and adiposity), suggesting that adjusting
      studies for these risk factors may be biologically inappropriate. Finally, we
      review the limited literature addressing the question of whether gout per se,
      above and beyond the presence of hyperuricemia, may convey an additional
      independent CVD risk. Given the ready ability of physicians to pharmacologically
      manage serum urate levels, a better understanding of the interaction between
      hyperuricemia, gout and vascular disease may be critical for the reduction of
      morbidity and mortality in high-risk CVD patients.

PMID- 19852753
TI  - Juvenile idiopathic arthritis--current and future therapies.
AB  - Juvenile idiopathic arthritis (JIA) consists of a group of heterogeneous
      disorders of chronic arthritis in childhoodwith no apparent cause. JIA is the
      most common rheumatic disease in children and may still result in signifcant
      morbidity, with joint deformity, growth impairment, and persistence of active
      arthritis into adulthood. In addition to arthritis, the extra-articular features
      that may be present in JIA, such as anterior uveitis or the fever of systemic
      onset JIA, are often the greater focus of therapy. Prior to the mid 1990s, the
      therapeutic armamentarium for JIA was more limited, utilizing nonspecifc agents,
      many with signifcant adverse effects. In the new era of target-specifc biologic
      therapy, the clinician is now able to better tailor therapy for patients with
      JIA. Still, despite the bells and whistles of biologics, the consistent
      performance of methotrexate as the gold standard disease-modifying anti-rheumatic
      drug (DMARD), against which all other agents are compared, cannot be
      overemphasized. Through continued translational research, rheumatologists better
      understand the biology behind the clinical symptoms. This review will discuss the
      clinical features of JIA, as well as past, present, and future therapeutic
      approaches in the care of children with arthritis.

PMID- 19852754
TI  - Necrotizing vasculitis--a 2009 update.
AB  - Necrotizing vasculitis continues to be a condition where difficult diagnostic and
      treatment decisions need to be made, with only a few well-done studies as
      clinical reference and support. New data suggest that both methotrexate and
      azathioprine may be effective agents for maintaining remission in
      antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis after
      remission is achieved with cyclophosphamide-based therapies. In addition,
      Behcet's syndrome appears to be more common than previously assumed and is likely
      more common than a combination of ANCA-associated vasculitis (AAV) syndromes.

PMID- 19852755
TI  - Development of hepatic fibrosis occurs normally in AMPK-deficient mice.
AB  - Inhibition or blockade of HSCs (hepatic stellate cells), the main matrix
      producing cells involved in the wound-healing response, represents an attractive
      strategy for the treatment of liver fibrosis. In vitro studies have shown that
      activation of AMPK (AMP-activated protein kinase), a key player in the regulation
      of cellular energy homoeostasis, inhibits proliferation of myofibroblasts derived
      from HSCs. If AMPK is a true regulator of fibrogenesis then defective AMPK
      activity would enhance fibrogenesis and hepatic fibrosis. To test this, in the
      present work, in vitro studies were performed on mouse primary HSCs treated or
      not with the AMPK activator AICAR (5-amino-4-imidazolecarboxamide ribonucleotide)
      or isolated from mice lacking the AMPKalpha1 catalytic subunit (AMPKalpha1-/-) or
      their littermates (AMPKalpha1+/+). Liver fibrosis was induced in vivo in
      AMPKalpha1-/- and AMPKalpha1+/+ mice by repeated injections of CCl(4) (carbon
      tetrachloride). During culture activation of HSCs, AMPK protein and activity
      significantly increased and regulatory AMPKgamma3 mRNA was specifically up
      regulated. Stimulation of AMPK activity by AICAR inhibited HSC proliferation, as
      expected, as well as collagen alpha1(I) expression. Importantly, AMPKalpha1
      deletion inhibited proliferation of HSCs, but not fibrogenesis, in vivo.
      Moreover, AMPKalpha1 deletion was not associated with enhanced CCl(4)-induced
      fibrosis in vivo. In conclusion, our present findings demonstrate that HSC
      transdifferentiation is associated with increased AMPK activity that could relate
      to the stabilization of AMPK complex by the gamma3 subunits. Activation of AMPK
      in HSCs inhibits in vitro fibrogenesis. By contrast, low AMPK activity does not
      prevent HSC activation in vitro nor in in vivo fibrosis.

PMID- 19852756
TI  - Peroxisome-proliferator-activated receptor-binding protein (PBP) is essential for
      the growth of active Notch4-immortalized mammary epithelial cells by activating
      SOX10 expression.
AB  - PBP (peroxisome-proliferator-activated receptor-binding protein) [Med1 (mediator
      1)/TRAP220 (thyroid-hormone-receptor-associated protein 220)] is essential for
      mammary gland development. We established a mammary epithelial cell line with a
      genotype of PBPLoxP/LoxP by expressing an active form of Notch4. Null mutation of
      PBP caused severe growth inhibition of the Notch4-immortalized mammary cells. We
      found that truncated PBP without the two LXXLL motifs could reverse the growth
      inhibition due to the deficiency of endogenous PBP, indicating that signalling
      through nuclear receptors is unlikely to be responsible for the growth inhibition
      as the result of PBP deficiency. Loss of PBP expression was shown to completely
      ablate the expression of SOX10 [Sry-related HMG (high-mobility group) box gene
      10]. The re-expression of SOX10 was capable of reversing the growth inhibition
      due to PBP deficiency, whereas suppressed expression of SOX10 inhibited the
      growth of Notch4-immortalized mammary cells. Further studies revealed PBP is
      directly recruited to the enhancer of the SOX10 gene, indicating that SOX10 is a
      direct target gene of PBP. We conclude that PBP is essential for the growth of
      Notch4-immortalized mammary cells by activating SOX10 expression, providing a
      potential molecular mechanism through which PBP regulates the growth of mammary
      stem/progenitor cells.

PMID- 19852757
TI  - Functional assessment of temperature-gated ion-channel activity using a real-time
      PCR machine.
AB  - The functional activity of a number of ion channels is highly sensitive to large
      changes in temperature. Foremost among these are the thermosensing TRP channels
      which include cold- (TRPM8, TRPA1), warmth- (TRPV3, TRPV4), and heat-sensing
      (TRPV1, TRPV2) members. TRPV1, also known as the vanilloid receptor (VR1), is
      activated by ligands such as capsaicin, acidic pH, and heat (an increase in
      temperature to approximately 42 degrees C will lead to channel opening).
      Screening against the thermal gating of TRPV1 is generally performed using
      perfusion systems or water baths for temperature control, in conjunction with
      electrophysiology or Ca2 + influx readouts for direct functional assessment.
      These approaches are very useful, but have limited throughput or minimal thermo
      temporal control. A standard real-time PCR machine with standard microplates
      allowed us to combine fluorescent Ca2 + detection with precise temperature
      manipulation to develop a homogeneous (Z' = 0.53), cell-based assay that uses
      temperature as the agonist. A temperature response curve of TRPV1 was obtained,
      which provided a T50 of 46.1 degrees C, and IC50 values against heat agonism were
      determined for known TRPV1 antagonists. Furthermore, we expanded this approach to
      a cold-activated ion channel, TRPM8. We developed and validated an analytical
      technique with broad applications for the study and screening of temperature
      gated ion channels.

PMID- 19852759
TI  - A novel method for sensitive and specific detection of DNA methylation biomarkers
      based on DNA restriction during PCR cycling.
AB  - DNA methylation is an important epigenetic mechanism involved in fundamental
      biological processes such as development, imprinting, and carcino-genesis. For
      these reasons, DNA methylation represents a valuable source for cancer
      biomarkers. Methods for the sensitive and specific detection of methylated DNA
      are a prerequisite for the implementation of DNA biomarkers into clinical routine
      when early detection based on the analysis of body fluids is desired. Here, a
      novel technique is presented for the detection of DNA methylation biomarkers,
      based on real-time PCR of bisulfite-treated template with enzymatic digestion of
      background DNA during amplification using the heat-stable enzyme Tsp509I. An
      assay for the lung cancer methylation biomarker BARHL2 was used to show clinical
      and analytical performance of the method in comparison with methylation-specific
      PCR technology. Both technologies showed comparable performance when analyzing
      technical DNA mixtures and bronchial lavage samples from 75 patients suspected of
      having lung cancer. The results demonstrate that the approach is useful for
      sensitive and specific detection of a few copies of methylated DNA in samples
      with a high background of unmethylated DNA, such as in clinical samples from body
      fluids.

PMID- 19852758
TI  - Arraycount, an algorithm for automatic cell counting in microwell arrays.
AB  - Microscale technologies have emerged as a powerful tool for studying and
      manipulating biological systems and miniaturizing experiments. However, the lack
      of software complementing these techniques has made it difficult to apply them
      for many high-throughput experiments. This work establishes Arraycount, an
      approach to automatically count cells in microwell arrays. The procedure consists
      of fluorescent microscope imaging of cells that are seeded in microwells of a
      microarray system and then analyzing images via computer to recognize the array
      and count cells inside each microwell. To start counting, green and red
      fluorescent images (representing live and dead cells, respectively) are extracted
      from the original image and processed separately. A template-matching algorithm
      is proposed in which pre-defined well and cell templates are matched against the
      red and green images to locate microwells and cells. Subsequently, local maxima
      in the correlation maps are determined and local maxima maps are thresholded. At
      the end, the software records the cell counts for each detected microwell on the
      original image in high-throughput. The automated counting was shown to be
      accurate compared with manual counting, with a difference of approximately 1-2
      cells per microwell: based on cell concentration, the absolute difference between
      manual and automatic counting measurements was 2.5-13%.

PMID- 19852760
TI  - An improved Huffman coding method for archiving text, images, and music
      characters in DNA.
AB  - An improved Huffman coding method for information storage in DNA is described.
      The method entails the utilization of modified unambiguous base assignment that
      enables efficient coding of characters. A plasmid-based library with efficient
      and reliable information retrieval and assembly with uniquely designed primers is
      described. We illustrate our approach by synthesis of DNA that encodes text,
      images, and music, which could easily be retrieved by DNA sequencing using the
      specific primers. The method is simple and lends itself to automated information
      retrieval.

PMID- 19852761
TI  - Cyclic stretch of the substratum using a shape-memory alloy induces directional
      migration in Dictyostelium cells.
AB  - Living cells are constantly subjected to various mechanical stimulations. They
      must sense the mechanical aspects of their environment and respond appropriately
      for proper cell function. In general, cells adhere to substrata. Thus, the cells
      must receive and respond to mechanical stimuli mainly from the substrata. For
      example, migrating cells can create their own polarity and migrate in a certain
      direction even in the absence of any attractive substance. In order to generate
      such polarity, cells must sense mechanical stimuli from the substrata and
      transduce these stimuli into intracellular signals. To investigate the
      relationship between signals derived from mechanical stimuli and related cell
      functions, one of the most commonly used techniques is the application of
      mechanical stimuli via stretching of elastic substrata. Here, we developed a new
      stretching device using a shape-memory alloy (SMA). An SMA has three advantages
      as an actuator of stretching devices: (i) the cost of the SMA required for the
      device is inexpensive, approximately 30 USD, (ii) the size of an SMA is very
      small (0.62 mm in diameter and 22 mm in length), and (iii) an SMA does not
      generate any vibrating noise, which can negatively affect cells. In response to
      the cyclic stretching by the new stretching device, Dictyostelium discoideum
      cells migrated perpendicular to the stretching direction and the migrating speed
      increased significantly. To our knowledge, this is the first report indicating
      that migrating cells can create their own polarity by the mechanical stimuli from
      the substrata.

PMID- 19852762
TI  - Direct pH measurements by using subcellular targeting of 5(and 6-)
      carboxyseminaphthorhodafluor in mammalian cells.
AB  - As a means of reliably measuring intracellular pH, we have precisely targeted
      5(and 6-) carboxyseminaphthorhodafluor to cellular subcompartments. This was
      accomplished by combining the well-established pH-sensitive dye with a protein
      based reporter system. When expressed in cells, the reporter protein is designed
      to covalently bind ligands composed of a functional group and a reactive linker.
      In order to make a pH-sensitive ligand, we chemically coupled the pH sensor to a
      reactive linker. Several ligands of differing linker lengths were made and tested
      for their pH responsiveness in vitro. The most responsive of these ligands was
      then evaluated for its efficacy in live cell labeling and its use as an
      intracellular pH sensor for ratiometric confocal microscopy. Here we show that we
      could target this pH sensor within mammalian cells exclusively to either the
      nucleus or cytoplasm. Exhibiting the versatility of this reporter technology, we
      were also able to specifically limit pH sensor labeling to within the trafficking
      pathway of integrins and directly measure pH of this environment. Results
      correspond well with previously published reports. Both the simplicity and
      flexibility of the technology used in this study make possible the development of
      diverse targeted microenvironmental sensors or other moieties of interest.

PMID- 19852763
TI  - Enhanced amplification of GC-rich DNA with two organic reagents.
AB  - Amplification of GC-rich DNA sequences is still a difficult task worldwide. Two
      frequently seen and inexpensive reagents-ethylene glycol and 1,2-propanediol-were
      found to be more effective than betaine in the amplification of 104 randomly
      selected GC-rich human DNA sequences with GC contents of 60-80% and lengths of
      700-800 bp.

PMID- 19852764
TI  - New clustering module in BDPC bisulfite sequencing data presentation and
      compilation web application for DNA methylation analyses.
AB  - The Bisulfite Sequencing Data Presentation and Compilation (BDPC) web interface
      for compilation and presentation of data from bisulfite sequencing DNA
      methylation studies has been improved by adding a new module. This module allows
      visualization of the whole data set in form of a heatmap of DNA methylation
      levels and clustering and comparison of tissue methylation patterns. It can also
      be used for data not processed by BDPC. In addition, several functions of the
      existing BDPC compilation module have been improved.

PMID- 19852765
TI  - A rapid method for titrating baculovirus stocks using the Sf-9 Easy Titer cell
      line.
AB  - A new rapid method for titrating baculovirus stocks has been developed using a
      novel cell line Sf-9 Easy Titer (Sf-9ET). The Sf-9ET cell line has been
      transfected with plasmid DNA containing the enhanced green fluorescent protein
      (eGFP) gene under the control of the baculovirus polyhedrin promoter. When used
      in the titration assay, the Sf-9ET cells turn green when they are infected with
      baculovirus due to the activation of the polyhedrin promoter/eGFP complex by
      baculovirus gene products expressed during the infection. Using a 96-well plate
      format end-point dilution assay, baculovirus titers can be determined in three
      days using a fluorescence microscope.

PMID- 19852766
TI  - Chaotic micromixing in open wells using audio-frequency acoustic microstreaming.
AB  - Mixing fluids for biochemical assays is problematic when volumes are very small
      (on the order of the 10 microL typical of single drops), which has inspired the
      development of many micromixing devices. In this paper, we show that micromixing
      is possible in the simple open wells of standard laboratory consumables using
      appropriate acoustic frequencies that can be applied using cheap, conventional
      audio components. Earlier work has shown that the phenomenon of acoustic
      microstreaming can mix fluids, provided that bubbles are introduced into a
      specially designed microchamber or that high-frequency surface acoustic wave
      devices are constructed. We demonstrate a key simplification: acoustic
      micromixing at audio frequencies by ensuring the system has a liquid-air
      interface with a small radius of curvature. The meniscus of a drop in a small
      well provided an appropriately small radius, and so an introduced bubble was not
      necessary. Microstreaming showed improvement over diffusion-based mixing by 1-2
      orders of magnitude. Furthermore, significant improvements are attainable through
      the utilization of chaotic mixing principles, whereby alternating fluid flow
      patterns are created by applying, in sequence, two different acoustic frequencies
      to a drop of liquid in an open well.

PMID- 19852767
TI  - Heterogeneous transition metal-based fluorescence polarization (HTFP) assay for
      probing protein interactions.
AB  - Analyses of protein interactions are fundamental for the investigation of
      molecular mechanisms responsible for cellular processes and diseases, as well as
      for drug discovery in the pharmaceutical industry. The present study details the
      development of a fluorescence polarization assay using melanoma inhibitory
      activity (MIA) protein-binding compounds and studies of the binding properties of
      this protein. Since they are dependent on the the lifetime of the fluorescent
      label, currently available fluorescence polarization assays can only determine
      interactions with either high- or low-molecular weight interaction partners. Our
      new approach eliminates this limitation by immobilizing a known binding partner
      of MIA protein to a well plate and by labeling the target protein using
      luminescent transition metal labels such as Ru(bpy)3 for binding studies with
      both high- and low-molecular weight interaction partners. Due to the use of a
      functionalized surface, we termed our concept heterogeneous transition metal
      based fluorescence polarization (HTFP) assay. The assay's independence from the
      molecular weight of potential binding partners should make the technique amenable
      to investigations on subjects as diverse as multimerization, interactions with
      pharmacophores, or binding affinity determination.

PMID- 19852768
TI  - A dual-activation, adenoviral-based system for the controlled induction of DNA
      double-strand breaks by the restriction endonuclease SacI.
AB  - Spontaneous damage to DNA is frequent and may lead to cell death, cell
      senescence, or mutations. DNA double-strand breaks (DSBs) are of special interest
      because they are highly toxic and have been implicated in neurodegeneration,
      cancer, and aging. Until now, there has not been a reliable system allowing
      tunable induction of random DSBs without affecting other macromolecules or cell
      functions. Here, we describe an adenoviral-based, doxycycline-mediated, and
      tamoxifen-dependent system for quantitative introduction of DSBs in mammalian
      cells. We generated a single adenoviral vector containing a tet-inducible,
      composite SacI restriction endonuclease/estrogen receptor (ERT2) gene, and a
      constitutively expressed reverse transactivator (rtTA) gene. Transduced mouse
      embryonic fibroblasts-as well as mouse liver cells in vivo-demonstrated a high
      level of DSBs in response to treatment with doxycycline and tamoxifen. We show
      that the amount of induced DSBs can be titrated by doxycycline dose and duration
      of treatment. This system should be useful for studying the processing of
      randomly induced DSBs and their effects on cell fate, without the side effects
      normally associated with radiation or chemical treatment.

PMID- 19852769
TI  - Reducing the impact of PCR-mediated recombination in molecular evolution and
      environmental studies using a new-generation high-fidelity DNA polymerase.
AB  - PCR-mediated recombination can greatly impact estimates of diversity, both in
      environmental studies and in analyses of gene family evolution. Here we measure
      chimera (PCR-mediated recombinant) formation by analyzing a mixture of eight
      partial actin sequences isolated from the amoeba Arcella hemisphaerica amplified
      under a variety of conditions that mimic standard laboratory situations. We
      further compare a new-generation proofreading processivity-enhanced polymerase to
      both a standard proofreading enzyme and previously published results.
      Proofreading polymerases are preferred over other polymerases in instances where
      evolutionary inferences must be made. Our analyses reveal that reducing the
      initial template concentration is as critical as reducing the number of cycles
      for decreasing chimera formation and improving accuracy. Furthermore, assessing
      the efficiency of recovery of original haplotypes demonstrates that multiple PCR
      reactions are required to capture the actual genetic diversity of a sample.
      Finally, the experiments confirm that processivity-enhanced polymerases enable a
      substantial decrease in PCR-mediated recombination through reducing starting
      template concentration, without compromising the robustness of PCR reactions.

PMID- 19852770
TI  - Using phiX174 DNA as an exogenous reference for measuring mitochondrial DNA copy
      number.
AB  - Quantitative real-time PCR has become a popular method to analyze and quantify
      changes in the copy number of mitochondrial DNA (mtDNA), and nuclear DNA (nDNA)
      is often used as an endogenous reference for mtDNA abundance. In our experience,
      using nDNA as a reference is problematic, due to differences in the extraction
      efficiency of nDNA and mtDNA and variation in the ploidy of experimental samples.
      Here, we report that the ratio of mtDNA to nDNA varies in repeated DNA
      extractions but that PhiX174 DNA, added before DNA extraction, is extracted with
      a similar efficiency to mtDNA, making it a suitable alternative reference for
      quantifying mtDNA copy number.

PMID- 19852771
TI  - A simplified, 96-well-adapted, ATP luminescence-based motility assay.
AB  - Directional motility assays make use of Boyden chambers or Transwell culture
      inserts with porous membranes that separate cells seeded in the upper chamber
      from a chemoattractant supplied in a lower chamber. These assays are often time
      consuming and are associated with several limitations due to manual counting and
      inconsistent results; low signal-to-noise ratio and fluorescence interference;
      and high cost and the need for specific equipment. Here, we describe a simple,
      direct, and easy ATP luminescence-based motility assay (ALMA), which can be used
      for 96-well plate quantification.

PMID- 19852772
TI  - Next-generation 9216-microwell cell arrays for high-content screening microscopy.
AB  - Reverse transfection on cell arrays is a high-throughput method for the parallel
      transfection of mammalian cells for use in high-content screening light
      microscopy. Here, we present novel 9216-microwell cell arrays which combine the
      advantages of multiwell plates (physically separated samples) and cell
      microarrays (high sample density and long-term storage).

PMID- 19852773
TI  - Comparative transcriptional survey between laser-microdissected cells from
      laminar abscission zone and petiolar cortical tissue during ethylene-promoted
      abscission in citrus leaves.
AB  - BACKGROUND: Abscission is the cell separation process by which plants are able to
      shed organs. It has a great impact on the yield of most crop plants. At the same
      time, the process itself also constitutes an excellent model to study cell
      separation processes, since it occurs in concrete areas known as abscission zones
      (AZs) which are composed of a specific cell type. However, molecular approaches
      are generally hampered by the limited area and cell number constituting the AZ.
      Therefore, detailed studies at the resolution of cell type are of great relevance
      in order to accurately describe the process and to identify potential candidate
      genes for biotechnological applications. RESULTS: Efficient protocols for the
      isolation of specific citrus cell types, namely laminar abscission zone (LAZ) and
      petiolar cortical (Pet) cells based on laser capture microdissection (LCM) and
      for RNA microextraction and amplification have been developed. A comparative
      transcriptome analysis between LAZ and Pet from citrus leaf explants subjected to
      an in-vitro 24 h ethylene treatment was performed utilising microarray
      hybridization and analysis. Our analyses of gene functional classes
      differentially represented in ethylene-treated LAZ revealed an activation program
      dominated by the expression of genes associated with protein synthesis, protein
      fate, cell type differentiation, development and transcription. The extensive
      repertoire of genes associated with cell wall biosynthesis and metabolism
      strongly suggests that LAZ layers activate both catabolic and anabolic wall
      modification pathways during the abscission program. In addition, over
      representation of particular members of different transcription factor families
      suggests important roles for these genes in the differentiation of the effective
      cell separation layer within the many layers contained in the citrus LAZ.
      Preferential expression of stress-related and defensive genes in Pet reveals that
      this tissue is likely to be reprogrammed to prevent pathogen attacks and general
      abiotic stresses after organ shedding. CONCLUSION: The LCM-based data generated
      in this survey represent the most accurate description of the main biological
      processes and genes involved in organ abscission in citrus. This study provides
      novel molecular insight into ethylene-promoted leaf abscission and identifies new
      putative target genes for characterization and manipulation of organ abscission
      in citrus.

PMID- 19852774
TI  - Patient with neuromyelitis optica and inflammatory demyelinating lesions
      comprising whole spinal cord from C2 level till conus: case report.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is an idiopathic, severe, inflammatory
      demyelinating disease of the central nervous system, that causes severe optic
      neuritis and myelitis attacks. Early discrimination between multiple sclerosis
      (MS) and NMO is important, as optimum treatment for both diseases may differ
      considerably. CASE PRESENTATION: We report a case of a patient who initially
      presented as longitudinally extensive transverse myelitis (LETM), having spastic
      upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and
      urinary incontinence, as well as extensive inflammatory spinal cord lesions from
      C2 level to conus. After 5 months the patient had another attack of transverse
      myelitis, had electrophysiological findings consistent with optic neuritis, was
      seropositive for NMO-IgG (aquaporin-4 IgG) and thus fulfilled NMO diagnostic
      criteria. Following treatment of disease attacks with pulse corticosteroid
      therapy and intravenous immunoglobulins, we included oral azathioprine in a
      combination with oral prednisone in the therapy. Since there was no significant
      clinical improvement, we decided to use cyclophosphamide therapy, which resulted
      in good clinical improvement and gradual decrease of cord swelling. CONCLUSION:
      In this NMO case report we wanted to emphasize the extensiveness of inflammatory
      spinal cord changes in our patient, from C2 level to conus. In the conclusion it
      is important to say that accurate, early diagnosis and distinction from MS is
      critical to facilitate initiation of immunosuppressive therapy for attack
      prevention.

PMID- 19852775
TI  - Characteristics of national registries for occupational diseases: international
      development and validation of an audit tool (ODIT).
AB  - BACKGROUND: The aim of the study was to develop quality indicators that can be
      used for quality assessment of registries of occupational diseases in relation to
      preventive policy on a national level. The research questions were: 1. Which
      indicators determine the quality of national registries of occupational diseases
      with respect to their ability to provide appropriate information for preventive
      policy? 2. What are the criteria that can distinguish low quality from high
      quality? METHODS: First, we performed a literature search to assess which output
      of registries can be considered appropriate for preventive policy and to develop
      a set of preliminary indicators and criteria. Second, final indicators and
      criteria were assessed and their content validity was tested in a Delphi study,
      for which experts from the 25 EU Member States were invited. RESULTS: The
      literature search revealed two different types of information output to be
      appropriate for preventive policy: monitor and alert information. For the
      evaluation of the quality of the monitor and alert function we developed ten
      indicators and criteria. Sixteen of the twenty-five experts responded in the
      first round of the Delphi study, and eleven in the second round. Based on their
      comments, we assessed the final nine indicators: the completeness of the
      notification form, coverage of registration, guidelines or criteria for
      notification, education and training of reporting physicians, completeness of
      registration, statistical methods used, investigation of special cases,
      presentation of monitor information, and presentation of alert information.
      Except for the indicator "coverage of registration" for the alert function, all
      the indicators met the preset requirements of content validity. CONCLUSION: We
      have developed quality indicators and criteria to evaluate registries for
      occupational diseases on the ability to provide appropriate information for
      preventive policy on a national level. Together, these indicators form a tool
      which can be used for quality improvement of registries of occupational diseases.

PMID- 19852776
TI  - Medical net cost of low alcohol consumption - a cause to reconsider improved
      health as the link between alcohol and wage?
AB  - BACKGROUND: Studies have found a positive effect of low/moderate alcohol
      consumption on wages. This has often been explained by referring to
      epidemiological research showing that alcohol has protective effects on certain
      diseases, i.e., the health link is normally justified using selected
      epidemiological information. Few papers have tested this link between alcohol and
      health explicitly, including all diseases where alcohol has been shown to have
      either a protective or a detrimental effect. AIM: Based on the full
      epidemiological information, we study the effect of low alcohol consumption on
      health, in order to determine if it is reasonable to explain the positive effect
      of low consumption on wages using the epidemiological literature. METHODS: We
      apply a non-econometrical cost-of-illness approach to calculate the medical care
      cost and episodes attributable to low alcohol consumption. RESULTS: Low alcohol
      consumption carries a net cost for medical care and there is a net benefit only
      for the oldest age group (80+). Low alcohol consumption also causes more episodes
      in medical care then what is saved, although inpatient care for women and older
      men show savings. CONCLUSION: Using health as an explanation in the alcohol-wage
      literature appears invalid when applying the full epidemiological information
      instead of selected information.

PMID- 19852777
TI  - Isolation and preservation of schistosome eggs and larvae in RNAlater(R)
      facilitates genetic profiling of individuals.
AB  - Although field-sampling procedures to capture gDNA from individual schistosome
      larval stages directly from their natural hosts exist, they do pose some
      technical and logistical challenges hampering certain epidemiological studies.
      The aim of this study was to develop, refine and evaluate an alternative
      methodology, which enables better preservation of large numbers of individual
      schistosome larval stages and eggs collected in low resource endemic areas, to
      provide PCR-quality DNA for multi-locus genetic analysis. The techniques reported
      here present simple and effective short-term field and long-term laboratory
      preservation and storage systems for individually sampled schistosome eggs and
      larval stages using a commercially available aqueous stabilisation reagent,
      RNAlater(R) eliminating the need for more cumbersome resources such as
      refrigerators, heaters and centrifuge equipment for immediate specimen
      processing. Adaptations to a general gDNA extraction method are described, that
      enables the acquisition of a gDNA extract (~50 mul), facilitating multiple
      molecular analyses of each sampled schistosome. The methodology provided PCR
      quality mitochondrial and nuclear DNA from laboratory cercariae, miracidia and
      eggs that had been stored at up to 37 degrees C for 2 weeks and at 4 degrees C
      for 6 months and also from field collected samples. This present protocol
      provides significant epidemiological, ethical and practical advantages over
      existing sampling methods and has the potential to be transferred to studies on
      other organisms, especially where specimens are unable to be seen by the naked
      eye, are difficult to handle and need to be obtained from a field environment.

PMID- 19852778
TI  - c-KIT positive Gastrointestinal Stromal Tumor presenting with acute bleeding in a
      patient with neurofibromatosis type 1: a case report.
AB  - BACKGROUND: Gastrointestinal stromal tumours are rare (GIST). However, the
      incidence of GIST among neurofibromatosis type 1 (NF-1) patients is approximately
      3.9-25%. GIST can present clinically in different ways such as abdominal pain,
      gastrointestinal bleeding and obstruction. CASE REPORT: We present 51 year female
      patient admitted with Background of neurofibromatosis type 1 admitted with
      melena. OGD has been done and showed duodenitis with large volume fresh blood in
      distal duodenum but no obvious bleeding point. Exploratory laparotomy revealed
      smooth nodular masses on the serosal surface of jejunum. Small bowel resection
      and side-to-side anastomosis were performed. Histopathoogical examination
      revealed small bowel gasrointestinal stromal tumour with low risk malignant
      potential. CONCLUSION: The incidence of GIST among neurofibromatosis type 1 (NF
      1) patients is not uncommon and we should pay attention to gastrointestinal
      manifestation in such patients.

PMID- 19852779
TI  - Next generation sequence analysis for mitochondrial disorders.
AB  - BACKGROUND: Mitochondrial disorders can originate from mutations in one of many
      nuclear genes controlling the organelle function or in the mitochondrial genome
      (mitochondrial DNA (mtDNA)). The large numbers of potential culprit genes,
      together with the little guidance offered by most clinical phenotypes as to which
      gene may be causative, are a great challenge for the molecular diagnosis of these
      disorders. METHODS: We developed a novel targeted resequencing assay for
      mitochondrial disorders relying on microarray-based hybrid capture coupled to
      next-generation sequencing. Specifically, we subjected the entire mtDNA genome
      and the exons and intron-exon boundary regions of 362 known or candidate
      causative nuclear genes to targeted capture and resequencing. We here provide
      proof-of-concept data by testing one HapMap DNA sample and two positive control
      samples. RESULTS: Over 94% of the targeted regions were captured and sequenced
      with appropriate coverage and quality, allowing reliable variant calling.
      Pathogenic mutations blindly tested in patients' samples were 100% concordant
      with previous Sanger sequencing results: a known mutation in Pyruvate
      dehydrogenase alpha 1 subunit (PDHA1), a novel splicing and a known coding
      mutation in Hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) were correctly
      identified. Of the additional variants recognized, 90 to 94% were present in
      dbSNP while 6 to 10% represented new alterations. The novel nonsynonymous
      variants were all in heterozygote state and mostly predicted to be benign. The
      depth of sequencing coverage of mtDNA was extremely high, suggesting that it may
      be feasible to detect pathogenic mtDNA mutations confounded by low level
      heteroplasmy. Only one sequencing lane of an eight lane flow cell was utilized
      for each sample, indicating that a cost-effective clinical test can be achieved.
      CONCLUSIONS: Our study indicates that the use of next generation sequencing
      technology holds great promise as a tool for screening mitochondrial disorders.
      The availability of a comprehensive molecular diagnostic tool will increase the
      capacity for early and rapid identification of mitochondrial disorders. In
      addition, the proposed approach has the potential to identify new mutations in
      candidate genes, expanding and redefining the spectrum of causative genes
      responsible for mitochondrial disorders.

PMID- 19852780
TI  - Determination of risk factors for hepatitis B and C in male patients suffering
      from chronic hepatitis.
AB  - BACKGROUND: Hepatitis B and C is common in Pakistan and various risk factors are
      attributable to its spread.One thousand and fifty consecutive male cases
      suffering from chronic liver disease (327 HBV and 723 HCV) were selected from the
      OPD of public sector hospital and a private clinic dealing exclusively with the
      liver patients. To compare the results 723 age and gender matched controls were
      selected from the blood transfusion services of the public sector hospital. A
      standard questionnaire was filled for all patients and controls which included
      the information on possible risk factors. FINDINGS: Family history of liver
      disease was significantly higher (43% and 34%) in HBV and HCV positive cases as
      compared to 5% in controls [odds ratio 15.6; 95% Confidence Interval CI: 10.1 -
      24.1, 10.9; 95% Confidence Interval CI: 7.3 - 16.4] and same trend was seen for
      death due to liver disease in the family. Majority 74% hepatitis B positive cases
      had their shaves done at communal barbers but this practice was equally prevalent
      amongst controls (68%), thus negating it as a possible risk factor, but there is
      a significant risk with p < 0.05 associated with HCV in male that get their shave
      in barber. Very strong association of the disease was found with history of
      dental treatment (38% HCV 36% HBV and 21% controls) [Odd ratio 2.3; 95% CI: 1.8
      3.0, Odd ratio 2.1; 95% CI: 1.5-2.8], surgery (23% HCV cases,14% HBV cases and
      12% controls), history of blood transfusion was significantly higher in HCV (6%)
      as compared to controls (2.1%) [Odd ratio 2.9; 95% CI: 1.5-5.5]. History of
      taking injections for various ailments by the general practitioners (over 90%
      patients in both hepatitis B and C cases) was significantly higher as compared to
      75% in controls [Odds ratio 3.8, 6.9; 95% CI: 2.4-6.1, 4.5-10.4] but
      hospitalization was not significant in HBV and HCV cases. CONCLUSION: Injections,
      surgery and dental treatment appear as major risk factors for the transmission of
      hepatitis B and C in the community. Massive health care awareness drives need to
      be done for both health care providers and the public to reduce this menace.

PMID- 19852781
TI  - Chemistry in second life.
AB  - This review will focus on the current level on chemistry research, education, and
      visualization possible within the multi-user virtual environment of Second Life.
      We discuss how Second Life has been used as a platform for the interactive and
      collaborative visualization of data from molecules and proteins to spectra and
      experimental data. We then review how these visualizations can be scripted for
      immersive educational activities and real-life collaborative research. We also
      discuss the benefits of the social networking affordances of Second Life for both
      chemists and chemistry students.

PMID- 19852782
TI  - Cholecystectomy and sphincterotomy in patients with mild acute biliary
      pancreatitis in Sweden 1988 - 2003: a nationwide register study.
AB  - BACKGROUND: Gallstones represent the most common cause of acute pancreatitis in
      Sweden. Epidemiological data concerning timing of cholecystectomy and
      sphincterotomy in patients with first attack of mild acute biliary pancreatitis
      (MABP) are scarce. Our aim was to analyse readmissions for biliary disease,
      cholecystectomy within one year, and mortality within 90 days of index admission
      for MABP. METHODS: Hospital discharge and death certificate data were linked for
      patients with first attack acute pancreatitis in Sweden 1988-2003. Mortality was
      calculated as case fatality rate (CFR) and standardized mortality ratio (SMR).
      MABP was defined as acute pancreatitis of biliary aetiology without mortality
      during an index stay of 10 days or shorter. Patients were analysed according to
      four different treatment policies: Cholecystectomy during index stay (group 1),
      no cholecystectomy during index stay but within 30 days of index admission (group
      2), sphincterotomy but not cholecystectomy within 30 days of index admission
      (group 3), and neither cholecystectomy nor sphincterotomy within 30 days of index
      admission (group 4). RESULTS: Of 11636 patients with acute biliary pancreatitis,
      8631 patients (74%) met the criteria for MABP. After exclusion of those with
      cholecystectomy or sphincterotomy during the year before index admission (N =
      212), 8419 patients with MABP remained for analysis. Patients in group 1 and 2
      were significantly younger than patients in group 3 and 4. Length of index stay
      differed significantly between the groups, from 4 (3-6) days, (representing
      median, 25 and 75 percentiles) in group 2 to 7 (5-8) days in groups 1. In group
      1, 4.9% of patients were readmitted at least once for biliary disease within one
      year after index admission, compared to 100% in group 2, 62.5% in group 3, and
      76.3% in group 4. One year after index admission, 30.8% of patients in group 3
      and 47.7% of patients in group 4 had undergone cholecystectomy. SMR did not
      differ between the four groups. CONCLUSION: Cholecystectomy during index stay
      slightly prolongs this stay, but drastically reduces readmissions for biliary
      indications.

PMID- 19852783
TI  - Galactorrhea associated with juvenile systemic lupus erythematosus: a review of
      the role of prolactin.
AB  - This case report is based on the clinical observation of a patient with juvenile
      systemic lupus erythematosus (SLE) who developed transient galactorrhea. The
      subsequent literature review documented an interesting association between
      prolactin and rheumatic diseases and in particular, hyperprolactinemia and SLE.
      The discussion that follows the case report explores this relationship and
      proposes a hypothesis regarding why this patient with juvenile SLE developed
      galactorrhea.

PMID- 19852784
TI  - Implementation research design: integrating participatory action research into
      randomized controlled trials.
AB  - BACKGROUND: A gap continues to exist between what is known to be effective and
      what is actually delivered in the usual course of medical care. The goal of
      implementation research is to reduce this gap. However, a tension exists between
      the need to obtain generalizeable knowledge through implementation trials, and
      the inherent differences between healthcare organizations that make standard
      interventional approaches less likely to succeed. The purpose of this paper is to
      explore the integration of participatory action research and randomized
      controlled trial (RCT) study designs to suggest a new approach for studying
      interventions in healthcare settings. DISCUSSION: We summarize key elements of
      participatory action research, with particular attention to its collaborative,
      reflective approach. Elements of participatory action research and RCT study
      designs are discussed and contrasted, with a complex adaptive systems approach
      used to frame their integration. SUMMARY: The integration of participatory action
      research and RCT design results in a new approach that reflects not only the
      complex nature of healthcare organizations, but also the need to obtain
      generalizeable knowledge regarding the implementation process.

PMID- 19852785
TI  - Joint contractures in the absence of inflammation may indicate
      mucopolysaccharidosis.
AB  - BACKGROUND: Undiagnosed patients with the attenuated form of
      mucopolysaccharidosis (MPS) type I often have joint symptoms in childhood that
      prompt referral to a rheumatologist. A survey conducted by Genzyme Corporation of
      60 European and Canadian rheumatologists and pediatric rheumatologists
      demonstrated that < 20% recognized signs and symptoms of MPS I or could identify
      appropriate diagnosis tests. These results prompted formation of an international
      working group of rheumatologists, pediatric rheumatologists, and experts on MPS I
      to formulate a rheumatology-based diagnostic algorithm. The resulting algorithm
      applies to all MPS disorders with musculoskeletal manifestations.Bone and joint
      manifestations are prominent among most patients with MPS disorders. These life
      threatening lysosomal storage diseases are caused by deficient activity of
      specific enzymes involved in the degradation of glycosaminoglycans. Patients with
      attenuated MPS disease often experience diagnostic delays. Enzyme replacement
      therapy is now commercially available for MPS I (laronidase), MPS II
      (idursulfase), and MPS VI (galsulfase). PRESENTATION OF THE HYPOTHESIS: Evolving
      joint pain and joint contractures in the absence of inflammation should always
      raise the suspicion of an MPS disorder. All such patients should undergo urinary
      glycosaminoglycan (uGAG) analysis (not spot tests for screening) in a reputable
      laboratory. Elevated uGAG levels and/or an abnormal uGAG pattern confirms an MPS
      disorder and specific enzyme testing will determine the MPS type. If uGAG
      analysis is unavailable and the patient exhibits any other common sign or symptom
      of an MPS disorder, such as corneal clouding, history of hernia surgery, frequent
      respiratory and/or ear, nose and throat infections; carpal tunnel syndrome, or
      heart murmur, proceed directly to enzymatic testing. Refer patients with
      confirmed MPS to a geneticist or metabolic specialist for further evaluation and
      treatment. TESTING OF THE HYPOTHESIS: We propose that rheumatologists, pediatric
      rheumatologists, and orthopedists consider our diagnostic algorithm when
      evaluating patients with joint pain and joint contractures. IMPLICATIONS OF THE
      HYPOTHESIS: Children and young adults can suffer for years and sometimes even
      decades with unrecognized MPS. Rheumatologists may facilitate early diagnosis of
      MPS based on the presenting signs and symptoms, followed by appropriate testing.
      Early diagnosis helps ensure prompt and appropriate treatment for these
      progressive and debilitating diseases.

PMID- 19852786
TI  - Pharmacokinetics and biodistribution of Erufosine in nude mice--implications for
      combination with radiotherapy.
AB  - BACKGROUND: Alkylphosphocholines represent promising antineoplastic drugs that
      induce cell death in tumor cells by primary interaction with the cell membrane.
      Recently we could show that a combination of radiotherapy with Erufosine, a
      paradigmatic intravenously applicable alkylphosphocholine, in vitro leads to a
      clear increase of irradiation-induced cell death. In view of a possible
      combination of Erufosine and radiotherapy in vivo we determined the
      pharmacokinetics and bioavailability as well as the tolerability of Erufosine in
      nude mice. METHODS: NMRI (nu/nu) nude mice were treated by intraperitoneal or
      subcutaneous injections of 5 to 40 mg/kg body weight Erufosine every 48 h for one
      to three weeks. Erufosine-concentrations were measured in brain, lungs, liver,
      small intestine, colon, spleen, kidney, stomach, adipoid tissue, and muscle by
      tandem-mass spectroscopy. Weight course, blood cell count and clinical chemistry
      were analyzed to evaluate general toxicity. RESULTS: Intraperitoneal injections
      were generally well tolerated in all dose groups but led to a transient loss of
      the bodyweight (<10%) in a dose dependent manner. Subcutaneous injections of high
      dose Erufosine caused local reactions at the injection site. Therefore, this
      regimen at 40 mg/kg body weight Erufosine was stopped after 14 days. No gross
      changes were observed in organ weight, clinical chemistry and white blood cell
      count in treated compared to untreated controls except for a moderate increase in
      lactate dehydrogenase and aspartate-aminotransferase after intensive treatment.
      Repeated Erufosine injections resulted in drug-accumulation in different organs
      with maximum concentrations of about 1000 nmol/g in spleen, kidney and lungs.
      CONCLUSION: Erufosine was well tolerated and organ-concentrations surpassed the
      cytotoxic drug concentrations in vitro. Our investigations establish the basis
      for a future efficacy testing of Erufosine in xenograft tumor models in nude mice
      alone and in combination with chemo- or radiotherapy.

PMID- 19852787
TI  - Panorametry: suggestion of a method for mandibular measurements on panoramic
      radiographs.
AB  - BACKGROUND: Orthopantomography (panoramic radiography) has been used for the
      study of measurements involving particularly the prediction of the eruption of
      impacted lower third molars and analyses of measurements of the ramus and head of
      mandible. The discrepancies involved with the projection of this radiographic
      image has stimulated the search for further ways to use it, particularly in
      orthodontic treatments and oral and maxillofacial surgeries. The author proposes
      a graphimetric method for the mandible, based on panoramic radiography. The
      results are expressed in linear and angular measurements, aiming at bilateral
      comparisons as well as the determination of the proportion of skeletal and dental
      structures, individually and among themselves as a whole. The method has been
      named Panorametry, and allows measurement of the mandible (Mandibular
      Panorametry) or the posterior mandibular teeth (Dental Panorametry). When
      combining mandible and maxilla, it should be referred to as Total Panorametry. It
      may also be used, in the future, with Cone Beam computed tomography (CT) images,
      and in this case it may be mentioned as CT Panorametry.

PMID- 19852788
TI  - Metabolomics: moving towards personalized medicine.
AB  - In many fields of medicine there is a growing interest in characterizing
      diseases at molecular level with a view to developing an individually tailored
      therapeutic approach. Metabolomics is a novel area that promises to contribute
      significantly to the characterization of various disease phenotypes and to the
      identification of personal metabolic features that can predict response to
      therapies. Based on analytical platforms such as mass spectrometry or NMR-based
      spectroscopy, the metabolomic approach enables a comprehensive overview of the
      metabolites, leading to the characterization of the metabolic fingerprint of a
      given sample. These metabolic fingerprints can then be used to distinguish
      between different disease phenotypes and to predict a drug's effectiveness and/or
      toxicity.Several studies published in the last few years applied the metabolomic
      approach in the field of pediatric medicine. Being a highly informative technique
      that can be used on samples collected non-invasively (e.g. urine or exhaled
      breath condensate), metabolomics has appeal for the study of pediatric diseases.
      Here we present and discuss the pediatric clinical studies that have taken the
      metabolomic approach.

PMID- 19852789
TI  - Safety and efficacy of oral DMSA therapy for children with autism spectrum
      disorders: Part A--medical results.
AB  - BACKGROUND: This study investigated the effect of oral dimercapto succinic acid
      (DMSA) therapy for children with autism spectrum disorders ages 3-8 years.
      METHODS: Phase 1 involved 65 children who received one round of DMSA (3 days).
      Participants who had high urinary excretion of toxic metals were selected to
      continue on to phase 2. In phase 2, 49 participants were randomly assigned in a
      double-blind design to receive an additional 6 rounds of either DMSA or placebo.
      RESULTS: DMSA greatly increased the excretion of lead, substantially increased
      excretion of tin and bismuth, and somewhat increased the excretion of thallium,
      mercury, antimony, and tungsten. There was some increase in urinary excretion of
      essential minerals, especially potassium and chromium. The Phase 1 single round
      of DMSA led to a dramatic normalization of RBC glutathione in almost all cases,
      and greatly improved abnormal platelet counts, suggesting a significant decrease
      in inflammation. CONCLUSION: Overall, DMSA therapy seems to be reasonably safe,
      effective in removing several toxic metals (especially lead), dramatically
      effective in normalizing RBC glutathione, and effective in normalizing platelet
      counts. Only 1 round (3 days) was sufficient to improve glutathione and
      platelets. Additional rounds increased excretion of toxic metals.

PMID- 19852790
TI  - Safety and efficacy of oral DMSA therapy for children with autism spectrum
      disorders: part B - behavioral results.
AB  - BACKGROUND: This study investigated the effects of oral dimercapto succinic acid
      (DMSA) therapy on the behavioural symptoms of children with autism spectrum
      disorders (ASD) ages 3-8 years. METHODS: Phase 1 involved 65 children with ASD
      who received one round of DMSA (3 days). Participants who had high urinary
      excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49
      participants were randomly assigned in a double-blind design to receive an
      additional 6 rounds of either DMSA or placebo. RESULTS: The groups receiving one
      round and seven rounds of DMSA had significant improvements on all the assessment
      measures. For the seven round group, the degree of improvement on the assessment
      measures could be partially explained by a regression analysis based on excretion
      of toxic metals and changes in glutathione (adjusted R2 of 0.28-0.75, p < 0.02 in
      all cases). One round of DMSA had nearly the same benefit as seven rounds. The
      assessment measures correlated reasonably with one another at the beginning of
      the study (r = 0.60-0.87) and even better at the end of the study (r = 0.63
      0.94). CONCLUSION: Overall, both one and seven rounds of DMSA therapy seems to be
      reasonably safe in children with ASD who have high urinary excretion of toxic
      metals, and possibly helpful in reducing some of the symptoms of autism in those
      children.

PMID- 19852791
TI  - Model and experiences of initiating collaboration with traditional healers in
      validation of ethnomedicines for HIV/AIDS in Namibia.
AB  - Many people with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome
      (HIV/AIDS) in Namibia have access to antiretroviral drugs but some still use
      traditional medicines to treat opportunistic infections and offset side-effects
      from antiretroviral medication. Namibia has a rich biodiversity of indigenous
      plants that could contain novel anti-HIV agents. However, such medicinal plants
      have not been identified and properly documented. Various ethnomedicines used to
      treat HIV/AIDS opportunistic infections have not been scientifically validated
      for safety and efficacy. These limitations are mostly attributable to the lack of
      collaboration between biomedical scientists and traditional healers. This paper
      presents a five-step contextual model for initiating collaboration with Namibian
      traditional healers in order that candidate plants that may contain novel anti
      HIV agents are identified, and traditional medicines used to treat HIV/AIDS
      opportunistic infections are subjected to scientific validation. The model
      includes key structures and processes used to initiate collaboration with
      traditional healers in Namibia; namely, the National Biosciences Forum, a
      steering committee with the University of Namibia (UNAM) as the focal point, a
      study tour to Zambia and South Africa where other collaborative frameworks were
      examined, commemorations of the African Traditional Medicine Day (ATMD), and
      consultations with stakeholders in north-eastern Namibia. Experiences from these
      structures and processes are discussed. All traditional healers in north-eastern
      Namibia were willing to collaborate with UNAM in order that their traditional
      medicines could be subjected to scientific validation. The current study provides
      a framework for future collaboration with traditional healers and the selection
      of candidate anti-HIV medicinal plants and ethnomedicines for scientific testing
      in Namibia.

PMID- 19852792
TI  - Oscillating magnetic field disrupts magnetic orientation in Zebra finches,
      Taeniopygia guttata.
AB  - BACKGROUND: Zebra finches can be trained to use the geomagnetic field as a
      directional cue for short distance orientation. The physical mechanisms
      underlying the primary processes of magnetoreception are, however, largely
      unknown. Two hypotheses of how birds perceive magnetic information are mainly
      discussed, one dealing with modulation of radical pair processes in retinal
      structures, the other assuming that iron deposits in the upper beak of the birds
      are involved. Oscillating magnetic fields in the MHz range disturb radical pair
      mechanisms but do not affect magnetic particles. Thus, application of such
      oscillating fields in behavioral experiments can be used as a diagnostic tool to
      decide between the two alternatives. METHODS: In a setup that eliminates all
      directional cues except the geomagnetic field zebra finches were trained to
      search for food in the magnetic north/south axis. The birds were then tested for
      orientation performance in two magnetic conditions. In condition 1 the horizontal
      component of the geomagnetic field was shifted by 90 degrees using a helmholtz
      coil. In condition 2 a high frequently oscillating field (1.156 MHz) was applied
      in addition to the shifted field. Another group of birds was trained to solve the
      orientation task, but with visual landmarks as directional cue. The birds were
      then tested for their orientation performance in the same magnetic conditions as
      applied for the first experiment. RESULTS: The zebra finches could be trained
      successfully to orient in the geomagnetic field for food search in the
      north/south axis. They were also well oriented in test condition 1, with the
      magnetic field shifted horizontally by 90 degrees. In contrast, when the
      oscillating field was added, the directional choices during food search were
      randomly distributed. Birds that were trained to visually guided orientation
      showed no difference of orientation performance in the two magnetic conditions.
      CONCLUSION: The results indicate that zebra finches use a receptor that bases on
      radical pair processes for sensing the direction of the earth magnetic field in
      this short distance orientation behavior.

PMID- 19852793
TI  - Prostaglandin treatment is associated with a withdrawal of progesterone and
      androgen at the receptor level in the uterine cervix.
AB  - Treatment with prostaglandin(PG)-E2 is clinically efficient for cervical priming.
      The aim of this study was to evaluate the impact of PG-E2 on the expression of
      the progesterone (PR), androgen (AR) and glucocorticoid (GR) receptors in human
      uterine cervix in prolonged pregnancy. The study groups were postterm nulliparous
      women with unripe cervices undergoing cervical priming with PG-E2 before labor
      induction. Responders (n = 12) who delivered vaginally were compared with non
      responders (n = 10), who underwent cesarean section due to failure to progress to
      the active phase of labor. Controls (n = 18) with vaginal partus at a normal
      gestational age served as a reference group. Cervical levels of PR-A and PR- B
      isoforms, AR and GR, serum levels of their ligands and sex hormone-binding
      globulin (SHBG) were quantified. The responder group displayed lower total PR-AB
      and AR protein levels as compared to non-responders, and lower PR-B and AR
      protein levels as compared to controls. In addition, the PR mRNA level was lower
      in responders as compared to non-responders. The GR protein level did not differ
      between the groups. We conclude that successful PG-E2 priming was followed by a
      progesterone and androgen withdrawal at the receptor level in the uterine cervix.

PMID- 19852794
TI  - TGF-beta inhibits IL-1beta-activated PAR-2 expression through multiple pathways
      in human primary synovial cells.
AB  - To investigate the mechanism how Transforming growth factor-beta(TGF-beta)
      represses Interleukin-1beta (IL-1beta)-induced Proteinase-Activated Receptor-2
      (PAR-2) expression in human primary synovial cells (hPSCs). Human chondrocytes
      and hPSCs isolated from cartilages and synovium of Osteoarthritis (OA) patients
      were cultured with 10% fetal bovine serum media or serum free media before
      treatment with IL-1beta, TGF-beta1, or Connective tissue growth factor (CTGF).
      The expression of PAR-2 was detected using reverse transcriptase-polymerase chain
      reaction (RT-PCR) and western blotting. Collagen zymography was performed to
      assess the activity of Matrix metalloproteinases-13 (MMP-13). It was demonstrated
      that IL-1beta induces PAR-2 expression via p38 pathway in hPSCs. This induction
      can be repressed by TGF-beta and was observed to persist for at least 48 hrs,
      suggesting that TGF-beta inhibits PAR-2 expression through multiple pathways.
      First of all, TGF-beta was able to inhibit PAR-2 activity by inhibiting IL-1beta
      induced p38 signal transduction and secondly the inhibition was also indirectly
      due to MMP-13 inactivation. Finally, TGF-beta was able to induce CTGF, and in
      turn CTGF represses PAR-2 expression by inhibiting IL-1beta-induced phospho-p38
      level. TGF-beta could prevent OA from progression with the anabolic ability to
      induce CTGF production to maintain extracellular matrix (ECM) integrity and to
      down regulate PAR-2 expression, and the anti-catabolic ability to induce Tissue
      inhibitors of metalloproteinase-3 (TIMP-3) production to inhibit MMPs leading to
      avoid PAR-2 over-expression. Because IL-1beta-induced PAR-2 expressed in hPSCs
      might play a significantly important role in early phase of OA, PAR-2 repression
      by exogenous TGF-beta or other agents might be an ideal therapeutic target to
      prevent OA from progression.

PMID- 19852795
TI  - Sublingual immunotherapy in children: facts and needs.
AB  - Allergen specific immunotherapy (SIT) is the practice of administering gradually
      increasing doses of the specific causative allergen to reduce the clinical
      reactivity of allergic subjects, and is the only treatment targeting the causes
      of hypersensitivity and not only the symptoms, as done by drugs. The traditional,
      subcutaneous immunotherapy (SCIT) was burdened by the problem of systemic
      reactions which may be sometimes severe and - though very rarely - even fatal.
      This was the background to develop non injections routes for SIT and particularly
      sublingual immunotherapy (SLIT), that emerged as a real treatment option for
      respiratory allergy.A number of studies was conducted to evaluate efficacy and
      safety of SLIT, the first meta-analysis - including 22 placebo-controlled trials 
      concluded for positive results in both issues, but the number of studies on
      children was too low to draw definite conclusions. Since then, many other studies
      became available and make possible to analyze SLIT in children in its well
      defined aspects as well as in sides still requiring more solid data.

PMID- 19852796
TI  - Suggestive linkage detected for blood pressure related traits on 2q and 22q in
      the population on the Samoan islands.
AB  - BACKGROUND: High blood pressure or hypertension is a major risk factor involved
      in the development of cardiovascular diseases. We conducted genome-wide variance
      component linkage analyses to search for loci influencing five blood pressure
      related traits including the quantitative traits systolic blood pressure (SBP),
      diastolic blood pressure (DBP) and pulse pressure (PP), the dichotomous trait
      hypertension (HT) and the bivariate quantitative trait SBP-DBP in families
      residing in American Samoa and Samoa, as well as in the combined sample from the
      two polities. We adjusted the traits for a number of environmental covariates
      such as smoking, alcohol consumption, physical activity and material life style.
      RESULTS: We found suggestive univariate linkage for SBP on chromosome 2q35-q37
      (LOD 2.4) and for PP on chromosome 22q13 (LOD 2.2), two chromosomal regions that
      recently have been associated with SBP and PP, respectively. CONCLUSION: We have
      detected additional evidence for a recently reported locus associated with SBP on
      chromosome 2q and a susceptibility locus for PP on chromosome 22q. However,
      differences observed between the results from our three partly overlapping
      genetically homogenous study samples from the Samoan islands suggest that
      additional studies should be performed in order to verify these results.

PMID- 19852797
TI  - GIFtS: annotation landscape analysis with GeneCards.
AB  - BACKGROUND: Gene annotation is a pivotal component in computational genomics,
      encompassing prediction of gene function, expression analysis, and sequence
      scrutiny. Hence, quantitative measures of the annotation landscape constitute a
      pertinent bioinformatics tool. GeneCards is a gene-centric compendium of rich
      annotative information for over 50,000 human gene entries, building upon 68 data
      sources, including Gene Ontology (GO), pathways, interactions, phenotypes,
      publications and many more. RESULTS: We present the GeneCards Inferred
      Functionality Score (GIFtS) which allows a quantitative assessment of a gene's
      annotation status, by exploiting the unique wealth and diversity of GeneCards
      information. The GIFtS tool, linked from the GeneCards home page, facilitates
      browsing the human genome by searching for the annotation level of a specified
      gene, retrieving a list of genes within a specified range of GIFtS value,
      obtaining random genes with a specific GIFtS value, and experimenting with the
      GIFtS weighting algorithm for a variety of annotation categories. The bimodal
      shape of the GIFtS distribution suggests a division of the human gene repertoire
      into two main groups: the high-GIFtS peak consists almost entirely of protein
      coding genes; the low-GIFtS peak consists of genes from all of the categories.
      Cluster analysis of GIFtS annotation vectors provides the classification of gene
      groups by detailed positioning in the annotation arena. GIFtS also provide
      measures which enable the evaluation of the databases that serve as GeneCards
      sources. An inverse correlation is found (for GIFtS>25) between the number of
      genes annotated by each source, and the average GIFtS value of genes associated
      with that source. Three typical source prototypes are revealed by their GIFtS
      distribution: genome-wide sources, sources comprising mainly highly annotated
      genes, and sources comprising mainly poorly annotated genes. The degree of
      accumulated knowledge for a given gene measured by GIFtS was correlated (for
      GIFtS>30) with the number of publications for a gene, and with the seniority of
      this entry in the HGNC database. CONCLUSION: GIFtS can be a valuable tool for
      computational procedures which analyze lists of large set of genes resulting from
      wet-lab or computational research. GIFtS may also assist the scientific community
      with identification of groups of uncharacterized genes for diverse applications,
      such as delineation of novel functions and charting unexplored areas of the human
      genome.

PMID- 19852798
TI  - Construction of an annotated corpus to support biomedical information extraction.
AB  - BACKGROUND: Information Extraction (IE) is a component of text mining that
      facilitates knowledge discovery by automatically locating instances of
      interesting biomedical events from huge document collections. As events are
      usually centred on verbs and nominalised verbs, understanding the syntactic and
      semantic behaviour of these words is highly important. Corpora annotated with
      information concerning this behaviour can constitute a valuable resource in the
      training of IE components and resources. RESULTS: We have defined a new scheme
      for annotating sentence-bound gene regulation events, centred on both verbs and
      nominalised verbs. For each event instance, all participants (arguments) in the
      same sentence are identified and assigned a semantic role from a rich set of 13
      roles tailored to biomedical research articles, together with a biological
      concept type linked to the Gene Regulation Ontology. To our knowledge, our scheme
      is unique within the biomedical field in terms of the range of event arguments
      identified. Using the scheme, we have created the Gene Regulation Event Corpus
      (GREC), consisting of 240 MEDLINE abstracts, in which events relating to gene
      regulation and expression have been annotated by biologists. A novel method of
      evaluating various different facets of the annotation task showed that average
      inter-annotator agreement rates fall within the range of 66% - 90%. CONCLUSION:
      The GREC is a unique resource within the biomedical field, in that it annotates
      not only core relationships between entities, but also a range of other important
      details about these relationships, e.g., location, temporal, manner and
      environmental conditions. As such, it is specifically designed to support bio
      specific tool and resource development. It has already been used to acquire
      semantic frames for inclusion within the BioLexicon (a lexical, terminological
      resource to aid biomedical text mining). Initial experiments have also shown that
      the corpus may viably be used to train IE components, such as semantic role
      labellers. The corpus and annotation guidelines are freely available for academic
      purposes.

PMID- 19852799
TI  - Suboptimal management of severe menopausal symptoms by Nigerian Gynaecologists: a
      call for mandatory continuing medical education for physicians.
AB  - BACKGROUND: Effective management of menopause is an important way to improve the
      quality of life of the increasing number of older women. The study sought to find
      out if Nigerian Gynaecologists offer effective treatment for severe menopausal
      symptoms. METHODS: 126 Nigerian Gynaecologists representing the six health zones
      of Nigeria were interviewed to determine the menopausal symptoms they had ever
      encountered in their practices, frequency of the symptoms, treatments ever
      offered for severe symptoms including their attitude to, and practice of hormone
      replacement therapy. RESULTS: A Nigerian Gynaecologist encountered an average of
      one patient with menopausal symptoms every three months (range: 0-3 patients per
      month). The commoner symptoms they encountered were hot flushes (88%), insomnia
      (75.4%), depression (58.0%), irritability (56.3%), night sweats (55.6%) and
      muscle pains (54.8%) while urinary symptoms (16.7%) and fracture (1.6%) were less
      common. Treatments ever offered for severe symptoms were reassurance (90.5%),
      anxiolytics (68.3%), analgesics (14.3), HRT (7.9%), Vitamins (4%), Beta-blockers
      (3.2%) and Danazol (2.4%). These treatments were offered as a matter of
      institutional traditions rather than being based on any evidence of their
      efficacy. CONCLUSION: The result revealed that most Nigerian Gynaecologists
      prefer reassurance and anxiolytics for managing severe menopausal symptoms
      instead of evidence-based effective therapies. A policy of mandatory continuing
      medical education for Nigerian physicians is recommended to ensure evidence-based
      management of gynaecological problems, including menopause.

PMID- 19852800
TI  - Downregulation of MIP-1alpha/CCL3 with praziquantel treatment in Schistosoma
      haematobium and HIV-1 co-infected individuals in a rural community in Zimbabwe.
AB  - BACKGROUND: Chemokines have been reported to play an important role in
      granulomatous inflammation during Schistosoma mansoni infection. However there is
      less information on their role in Schistosoma haematobium infection, or on the
      effect of concurrent HIV-1 infection, as a potential modifying influence.
      METHODS: To determine levels of MIP-1alpha/CCL3 chemokine in plasma of S.
      haematobium and HIV-1 co-infected and uninfected individuals in a rural black
      Zimbabwean community.A cohort was established of HIV-1 and schistosomiasis
      infection and co-infection comprising 379 participants. Outcome measures
      consisted of HIV-1 and schistosomiasis status and levels of MIP-1alpha/CCL3 in
      plasma at baseline and three months post treatment. An association was
      established between MIP-1alpha/CCL3 plasma levels with HIV-1 and S. haematobium
      infections. RESULTS: A total of 379 adults formed the established cohort
      comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62
      years. The median MIP-1alpha/CCL3 plasma concentration was significantly higher
      in S. haematobium infected compared with uninfected individuals (p = 0.029). In
      contrast, there was no difference in the median MIP-1alpha/CCL3 levels between
      HIV-1 positive and negative individuals (p = 0.631). MIP-1alpha/CCL3
      concentration in plasma was significantly reduced at three months after treatment
      with praziquantel (p = 000). CONCLUSION: The results of our study show that the
      MIP-1alpha/CCL3 levels were positively associated with S. haematobium egg counts
      at baseline but not with HIV-1 infection status. MIP-1alpha/CCL3 levels were
      significantly reduced at three months post treatment with praziquantel. We
      therefore conclude that MIP-1alpha/CCL3 is produced during infection with S
      haematobium. S. haematobium infection is associated with increased MIP
      1alpha/CCL3 levels in an egg intensity-dependent manner and treatment of S.
      haematobium is associated with a reduction in MIP-1alpha/CCL3.

PMID- 19852801
TI  - Predictive factors for breast cancer in patients diagnosed atypical ductal
      hyperplasia at core needle biopsy.
AB  - BACKGROUND: Percutaneous core needle biopsy (CNB) is considered to be the
      standard technique for histological diagnosis of breast lesions. But, it is less
      reliable for diagnosing atypical ductal hyperplasia (ADH). The purpose of the
      present study was to predict, based on clinical and radiological findings, which
      cases of ADH diagnosed by CNB would be more likely to be associated with a more
      advanced lesion on subsequent surgical excision. METHODS: Between February 2002
      and December 2007, consecutive ultrasound-guided CNBs were performed on
      suspicious breast lesions at Seoul St. Mary's Hospital. A total of 69 CNBs led to
      a diagnosis of ADH, and 45 patients underwent follow-up surgical excision. We
      reviewed the medical records and analyses retrospectively. RESULTS: Sixty-nine
      patients were diagnosed with ADH at CNB. Of these patients, 45 underwent surgical
      excision and 10 (22.2%) were subsequently diagnosed with a malignancy (ductal
      carcinoma in situ, n = 8; invasive cancer, n = 2). Univariate analysis revealed
      age (>or= 50-years) at the time of core needle biopsy (p = 0.006), size (> 10 mm)
      on imaging (p = 0.033), and combined mass with microcalcification on sonography
      (p = 0.029) to be associated with underestimation. When those three factors were
      included in multivariate analysis, only age (p = 0.035, HR 6.201, 95% CI 1.135
      33.891) was an independent predictor of malignancy. CONCLUSION: Age (>or= 50) at
      the time of biopsy is an independent predictive factor for breast cancer at
      surgical excision in patients with diagnosed ADH at CNB. For patients diagnosed
      with ADH at CNB, only complete surgical excision is the suitable treatment
      option, because we could not find any combination of factors that can safely
      predict the absence of DCIS or invasive cancer in a case of ADH.

PMID- 19852802
TI  - Characterization of immunoglobulin G antibodies to Plasmodium falciparum
      sporozoite surface antigen MB2 in malaria exposed individuals.
AB  - BACKGROUND: MB2 protein is a sporozoite surface antigen on the human malaria
      parasite Plasmodium falciparum. MB2 was identified by screening a P. falciparum
      sporozoite cDNA expression library using immune sera from a protected donor
      immunized via the bites of P. falciparum-infected irradiated mosquitoes. It is
      not known whether natural exposure to P. falciparum also induces the anti-MB2
      response and if this response differs from that in protected individuals
      immunized via the bites of P. falciparum infected irradiated mosquitoes. The anti
      MB2 antibody response may be part of a robust protective response against the
      sporozoite. METHODS: Fragments of polypeptide regions of MB2 were constructed as
      recombinant fusions sandwiched between glutathione S-transferase and a hexa
      histidine tag for bacterial expression. The hexa histidine tag affinity purified
      proteins were used to immunize rabbits and the polyclonal sera evaluated in an in
      vitro inhibition of sporozoite invasion assay. The proteins were also used in
      immunoblots with sera from a limited number of donors immunized via the bites of
      P. falciparum infected irradiated mosquitoes and plasma and serum obtained from
      naturally exposed individuals in Kenya. RESULTS: Rabbit polyclonal antibodies
      targeting the non-repeat region of the basic domain of MB2 inhibited sporozoites
      entry into HepG2-A16 cells in vitro. Analysis of serum from five human volunteers
      that were immunized via the bites of P. falciparum infected irradiated mosquitoes
      that developed immunity and were completely protected against subsequent
      challenge with non-irradiated parasite also had detectable levels of antibody
      against MB2 basic domain. In contrast, in three volunteers not protected, anti
      MB2 antibodies were below the level of detection. Sera from protected volunteers
      preferentially recognized a non-repeat region of the basic domain of MB2, whereas
      plasma from naturally-infected individuals also had antibodies that recognize
      regions of MB2 that contain a repeat motif in immunoblots. Sequence analysis of
      eleven field isolates and four laboratory strains showed that these antigenic
      regions of the basic domain of the MB2 gene are highly conserved in parasites
      obtained from different parts of the world. Moreover, anti-MB2 antibodies also
      were detected in the plasma of 83% of the individuals living in a malaria endemic
      area of Kenya (n = 41). CONCLUSION: A preliminary analysis of the human humoral
      response against MB2 indicates that it may be an additional highly conserved
      target for immune intervention at the pre-erythrocytic stage of P. falciparum
      life cycle.

PMID- 19852803
TI  - Measuring disease-specific quality of life in rare populations: a practical
      approach to cross-cultural translation.
AB  - BACKGROUND: Disease-specific quality of life (QoL) measures have enhanced the
      capacity of outcome measures to evaluate subtle changes and differences between
      groups. However, when the specific disease is rare, the cohort of patients is
      small and international collaboration is often necessary to accomplish meaningful
      research. As many of the QoL measures have been developed in North American
      English, they require translation to ensure their usefulness in a multi-cultural
      and/or international society. Published guidelines provide formal methods to
      achieve cross-culturally comparable versions of a QoL tool. However, these
      guidelines describe a rigorous process that is not always feasible, particularly
      in rare disease groups. The objective of this manuscript is to describe the
      process that was developed to achieve accurate cross-cultural translations of a
      disease-specific QoL measure, to overcome the challenges of a small sample size,
      i.e. children with a rare disorder. PROCEDURE: A measurement study was conducted
      in the United Kingdom (UK), France, Germany and Uruguay, during which the
      validated measure was translated into the languages of the respective countries.
      RESULTS: This is a report of a modified, child-centric, cross-cultural
      translation and adaptation process in which culturally appropriate and
      methodologically valid translations of a disease-specific QoL measure, the Kids'
      ITP Tools (KIT), were performed in children with immune thrombocytopenic purpura
      (ITP). The KIT was translated from North American English into UK English,
      French, German, and Spanish. CONCLUSION: This study was a successful
      international collaboration. The modified process through which culturally
      appropriate and methodologically valid translations of QoL measures may be
      achieved in a pediatric population with a relatively rare disorder is reported.

PMID- 19852804
TI  - Local cell metrics: a novel method for analysis of cell-cell interactions.
AB  - BACKGROUND: The regulation of many cell functions is inherently linked to cell
      cell contact interactions. However, effects of contact interactions among
      adherent cells can be difficult to detect with global summary statistics due to
      the localized nature and noise inherent to cell-cell interactions. The lack of
      informatics approaches specific for detecting cell-cell interactions is a
      limitation in the analysis of large sets of cell image data, including
      traditional and combinatorial or high-throughput studies. Here we introduce a
      novel histogram-based data analysis strategy, termed local cell metrics (LCMs),
      which addresses this shortcoming. RESULTS: The new LCM method is demonstrated via
      a study of contact inhibition of proliferation of MC3T3-E1 osteoblasts. We
      describe how LCMs can be used to quantify the local environment of cells and how
      LCMs are decomposed mathematically into metrics specific to each cell type in a
      culture, e.g., differently-labelled cells in fluorescence imaging. Using this
      approach, a quantitative, probabilistic description of the contact inhibition
      effects in MC3T3-E1 cultures has been achieved. We also show how LCMs are related
      to the naive Bayes model. Namely, LCMs are Bayes class-conditional probability
      functions, suggesting their use for data mining and classification. CONCLUSION:
      LCMs are successful in robust detection of cell contact inhibition in situations
      where conventional global statistics fail to do so. The noise due to the random
      features of cell behavior was suppressed significantly as a result of the focus
      on local distances, providing sensitive detection of cell-cell contact effects.
      The methodology can be extended to any quantifiable feature that can be obtained
      from imaging of cell cultures or tissue samples, including optical, fluorescent,
      and confocal microscopy. This approach may prove useful in interpreting culture
      and histological data in fields where cell-cell interactions play a critical role
      in determining cell fate, e.g., cancer, developmental biology, and tissue
      regeneration.

PMID- 19852805
TI  - Sero-prevalence of latent Toxoplasma gondii infection among HIV-infected and HIV
      uninfected people in Addis Ababa, Ethiopia: A comparative cross-sectional study.
AB  - BACKGROUND: Toxoplasmosis in immuno-compromised hosts manifests primarily as a
      life threatening condition, toxoplasmic encephalitis. However, there is scarce
      information about the magnitude of Toxoplasma gondii infection among HIV-infected
      people in Ethiopia. This study was, therefore, conducted to determine the sero
      prevalence of T. gondii infection among HIV-infected and HIV-uninfected subjects.
      FINDINGS: Sera were collected from people with and without HIV infection for the
      purpose of studying hepatitis B virus (HBV) at St. Paul Hospital, Addis Ababa,
      Ethiopia from 24 January 2007 to 15 February 2007. Among these sera, the first
      330 consecutive sera, 165 from each HIV sero-group, were selected and tested for
      anti-T. gondii IgG antibodies using Enzyme Linked Immunosorbent Assay. The
      seroprevalence of Toxoplasma infection was assessed against socio-demographic
      characteristics, HIV and HBV serostatus and HBV-related risk factors. The overall
      sero-prevalence of latent T. gondii infection among the study subjects was 90.0%.
      Toxoplasma infection was observed with respective prevalence of 93.3% and 86.7%
      among HIV-infected and HIV-uninfected people. Though Toxoplasma infection seems
      to be influenced by age, gender and HIV serostatus, only HBV serostatus was
      significantly associated (OR 2.71, CI 1.12 to 6.57) in multivariate logistic
      regression analysis. CONCLUSION: The seroprevalence of latent T. gondii infection
      is high and similar by HIV status. Educating people to prevent acquisition of new
      Toxoplasma infection and minimizing the risk of disease manifestations among HIV
      Toxoplasma co-infected individuals is important.

PMID- 19852806
TI  - SNP_tools: A compact tool package for analysis and conversion of genotype data
      for MS-Excel.
AB  - BACKGROUND: Single nucleotide polymorphism (SNP) genotyping is a major activity
      in biomedical research. Scientists prefer to have a facile access to the results
      which may require conversions between data formats. First hand SNP data is often
      entered in or saved in the MS-Excel format, but this software lacks genetic and
      epidemiological related functions. A general tool to do basic genetic and
      epidemiological analysis and data conversion for MS-Excel is needed. FINDINGS:
      The SNP_tools package is prepared as an add-in for MS-Excel. The code is written
      in Visual Basic for Application, embedded in the Microsoft Office package. This
      add-in is an easy to use tool for users with basic computer knowledge (and
      requirements for basic statistical analysis). CONCLUSION: Our implementation for
      Microsoft Excel 2000-2007 in Microsoft Windows 2000, XP, Vista and Windows 7 beta
      can handle files in different formats and converts them into other formats. It is
      a free software.

PMID- 19852807
TI  - Characterizing multisegment foot kinematics during gait in diabetic foot
      patients.
AB  - BACKGROUND: The prevalence of diabetes mellitus has reached epidemic proportions,
      this condition may result in multiple and chronic invalidating long term
      complications. Among these, the diabetic foot, is determined by the simultaneous
      presence of both peripheral neuropathy and vasculopathy that alter the
      biomechanics of the foot with the formation of callosity and ulcerations. To
      diagnose and treat the diabetic foot is crucial to understand the foot complex
      kinematics. Most of gait analysis protocols represent the entire foot as a rigid
      body connected to the shank. Nevertheless the existing multisegment models cannot
      completely decipher the impairments associated with the diabetic foot. METHODS: A
      four segment foot and ankle model for assessing the kinematics of the diabetic
      foot was developed. Ten normal subjects and 10 diabetics gait patterns were
      collected and major sources of variability were tested. Repeatability analysis
      was performed both on a normal and on a diabetic subject. Direct skin marker
      placement was chosen in correspondence of 13 anatomical landmarks and an
      optoelectronic system was used to collect the data. RESULTS: Joint rotation
      normative bands (mean plus/minus one standard deviation) were generated using the
      data of the control group. Three representative strides per subject were
      selected. The repeatability analysis on normal and pathological subjects results
      have been compared with literature and found comparable. Normal and pathological
      gait have been compared and showed major statistically significant differences in
      the forefoot and midfoot dorsi-plantarflexion. CONCLUSION: Even though various
      biomechanical models have been developed so far to study the properties and
      behaviour of the foot, the present study focuses on developing a methodology for
      the functional assessment of the foot-ankle complex and for the definition of a
      functional model of the diabetic neuropathic foot. It is, of course, important to
      evaluate the major sources of variation (true variation in the subject's gait and
      artefacts from the measurement procedure). The repeatability of the protocol was
      therefore examined, and results showed the suitability of this method both on
      normal and pathological subjects. Comparison between normal and pathological
      kinematics analysis confirmed the validity of a similar approach in order to
      assess neuropathics biomechanics impairment.

PMID- 19852808
TI  - Multilocus sequence typing of Cronobacter sakazakii and Cronobacter malonaticus
      reveals stable clonal structures with clinical significance which do not
      correlate with biotypes.
AB  - BACKGROUND: The Cronobacter genus (Enterobacter sakazakii) has come to prominence
      due to its association with infant infections, and the ingestion of contaminated
      reconstituted infant formula. C. sakazakii and C. malonaticus are closely
      related, and are defined according their biotype. Due to the ubiquitous nature of
      the organism, and the high severity of infection for the immunocompromised, a
      multilocus sequence typing (MLST) scheme has been developed for the fast and
      reliable identification and discrimination of C. sakazakii and C. malonaticus
      strains. It was applied to 60 strains of C. sakazakii and 16 strains of C.
      malonaticus, including the index strains used to define the biotypes. The strains
      were from clinical and non-clinical sources between 1951 and 2008 in USA, Canada,
      Europe, New Zealand and the Far East. RESULTS: This scheme uses 7 loci; atpD,
      fusA, glnS, gltB, gyrB, infB, and pps. There were 12 sequence types (ST)
      identified in C. sakazakii, and 3 in C. malonaticus. A third (22/60) of C.
      sakazakii strains were in ST4, which had almost equal numbers of clinical and
      infant formula isolates from 1951 to 2008. ST8 may represent a particularly
      virulent grouping of C. sakazakii as 7/8 strains were clinical in origin which
      had been isolated between 1977 - 2006, from four countries. C. malonaticus
      divided into three STs. The previous Cronobacter biotyping scheme did not clearly
      correspond with STs nor with species. CONCLUSION: In conclusion, MLST is a more
      robust means of identifying and discriminating between C. sakazakii and C.
      malonaticus than biotyping. The MLST database for these organisms is available
      online at http://pubmlst.org/cronobacter/.

PMID- 19852809
TI  - Nme protein family evolutionary history, a vertebrate perspective.
AB  - BACKGROUND: The Nme family, previously known as Nm23 or NDPK, is involved in
      various molecular processes including tumor metastasis and some members of the
      family, but not all, exhibit a Nucleoside Diphosphate Kinase (NDPK) activity. Ten
      genes are known in humans, in which some members have been extensively studied.
      In non-mammalian species, the Nme protein family has received, in contrast, far
      less attention. The picture of the vertebrate Nme family remains thus incomplete
      and orthology relationships with mammalian counterparts were only partially
      characterized. The present study therefore aimed at characterizing the Nme gene
      repertoire in vertebrates with special interest for teleosts, and providing a
      comprehensive overview of the Nme gene family evolutionary history in
      vertebrates. RESULTS: In the present study, we present the evolutionary history
      of the Nme family in vertebrates and characterize the gene family repertoire for
      the first time in several non-mammalian species. Our observations show that
      vertebrate Nme genes can be separated in two evolutionary distinct groups. Nme1,
      Nme2, Nme3, and Nme4 belong to Group I while vertebrate Nme5, Nme6, Nme7, Nme8,
      and Nme9 belong to Group II. The position of Nme10 is in contrast more debatable
      due to its very specific evolutionary history. The present study clearly
      indicates that Nme5, Nme6, Nme7, and Nme8 originate from duplication events that
      occurred before the chordate radiation. In contrast, Nme genes of the Group I
      have a very different evolutionary history as our results suggest that they all
      arise from a common gene present in the chordate ancestor. In addition,
      expression patterns of all zebrafish nme transcripts were studied in a broad
      range of tissues by quantitative PCR and discussed in the light of the function
      of their mammalian counterparts. CONCLUSION: This work offers an evolutionary
      framework that will pave the way for future studies on vertebrate Nme proteins
      and provides a unified vertebrate Nme nomenclature that is consistent with the
      nomenclature in use in mammals. Based on protein structure and expression data,
      we also provide new insight into molecular functions of Nme proteins among
      vertebrates and raise intriguing questions on the roles of Nme proteins in
      gonads.

PMID- 19852811
TI  - Use of short message service (SMS) to improve malaria chemoprophylaxis compliance
      after returning from a malaria endemic area.
AB  - BACKGROUND: Malaria chemoprophylaxis compliance is suboptimal among French
      soldiers despite the availability of free malaria chemoprophylaxis and repeated
      health education before, during and after deployment to malaria endemic areas.
      METHODS: In 2007, a randomized controlled study was performed among a cohort of
      French soldiers returning from Cote d'Ivoire to assess the feasibility and
      acceptability of sending a daily short message service (SMS) reminder message via
      mobile device to remind soldiers to take their malaria chemoprophylaxis, and to
      assess the impact of the daily reminder SMS on chemoprophylaxis compliance.
      Malaria chemoprophylaxis consisted of a daily dose of 100 mg doxycycline
      monohydrate, which began upon arrival in Cote d'Ivoire and was to be continued
      for 28 days following return to France. Feasibility and acceptability were
      assessed by questionnaire. Cohort members were followed for a 28 day period, with
      compliance assessed by use of an electronic medication monitoring device, from
      which several indicators were developed: daily proportion of compliant
      individuals, average number of pills taken, and early discontinuation. RESULTS:
      Among 424 volunteers randomized to the study, 47.6% were assigned to the SMS
      group and 52.3% to the control group. Approximately 90% of subjects assigned to
      the SMS group received a daily SMS at midday during the study. Persons of the SMS
      group agreed more frequently that SMS reminders were very useful and that the
      device was not annoying. Compliance did not vary significantly between groups
      across the compliance indicators. CONCLUSION: SMS did not increase malaria
      chemoprophylaxis compliance above baseline, likely because the persons did not
      benefit from holidays after the return and stayed together. So the reminder by
      SMS was noted by all subjects of the study. Another study should be done to
      confirm these results on soldiers going on holidays from employment after return
      or with individual travellers.

PMID- 19852810
TI  - AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members,
      activates the SAPK/JNK pathway and enhances radiation-induced apoptosis.
AB  - BACKGROUND: Gossypol, a naturally occurring polyphenolic compound has been
      identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins.
      It induces apoptosis in a wide range of tumor cell lines and enhances
      chemotherapy- and radiation-induced cytotoxicity both in vitro and in vivo. Bcl-2
      and related proteins are important inhibitors of apoptosis and frequently
      overexpressed in human tumors. Increased levels of these proteins confer radio-
      and chemoresistance and may be associated with poor prognosis. Consequently,
      inhibition of the anti-apoptotic functions of Bcl-2 family members represents a
      promising strategy to overcome resistance to anticancer therapies. METHODS: We
      tested the effect of (-)-gossypol, also denominated as AT-101, radiation and the
      combination of both on apoptosis induction in human leukemic cells, Jurkat T and
      U937. Because activation of the SAPK/JNK pathway is important for apoptosis
      induction by many different stress stimuli, and Bcl-X(L) is known to inhibit
      activation of SAPK/JNK, we also investigated the role of this signaling cascade
      in AT-101-induced apoptosis using a pharmacologic and genetic approach. RESULTS:
      AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED50 values
      of 1.9 and 2.4 microM in Jurkat T and U937 cells, respectively. Isobolographic
      analysis revealed a synergistic interaction between AT-101 and radiation, which
      also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK
      which was blocked by the kinase inhibitor SP600125. In cells overexpressing a
      dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly
      reduced. CONCLUSION: Our data show that AT-101 strongly enhances radiation
      induced apoptosis in human leukemic cells and indicate a requirement for the
      SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation
      may overcome treatment resistance and lead to the development of new effective
      combination therapies.

PMID- 19852812
TI  - Osteopontin and the C-terminal peptide of thrombospondin-4 compete for CD44
      binding and have opposite effects on CD133+ cell colony formation.
AB  - BACKGROUND: C21, the C-terminal peptide of thrombospondin-4, has growth promoting
      activity and was discovered as one of several erythropoietin-dependent
      endothelial proteins. C21 stimulates red cell formation in anemic mice and is a
      growth factor for CD34+ and CD36+ hematopoietic cells, skin fibroblasts and
      kidney epithelial cells. ROD1 has been identified as an intracellular mediator.
      Nothing is known about the existence of putative C21 receptors on plasma
      membranes of target cells. FINDINGS: We analyzed the nature of C21-binding
      proteins in cell lysates of skin fibroblasts using C21 affinity columns. The
      membrane receptor CD44 was identified as C21-binding protein by mass
      spectrometry. We were unable to demonstrate any direct involvement of CD44 on
      cell growth or the effect of C21 on cell proliferation. A soluble form of CD44
      was synthesized in insect cells and purified from culture supernatants with a
      combination of PVDF filtration in the presence of ammonium sulphate and HPLC.
      Both osteopontin and hyaluronic acid competitively displaced Biotin-C21 binding
      to CD44. In a colony-forming assay using primitive CD133+ hematopoietic stem
      cells from cord blood, osteopontin and C21 had opposite effects and C21 reduced
      the inhibitory action of osteopontin. CONCLUSION: CD44 is a C21-binding membrane
      protein. We could not demonstrate an involvement of CD44 in the proliferative
      action of C21. Nevertheless, based on the antagonism of C21 and osteopontin in
      hematopoietic precursors, we speculate that C21 could indirectly have a major
      impact on hematopoietic stem cell proliferation, by hindering osteopontin
      membrane binding at the level of the bone marrow niche.

PMID- 19852813
TI  - Aetiology of thrombosed external haemorrhoids: a questionnaire study.
AB  - BACKGROUND: It is important to better understand the aetiology of thrombosed
      external haemorrhoids (TEH) because recurrence rates are high, prophylaxis is
      unknown, and optimal therapy is highly debated. FINDINGS: We conducted a
      questionnaire study of individuals with and without TEH. Aetiology was studied by
      comparison of answers to a questionnaire given to individuals with and without
      TEH concerning demography, history, and published aetiologic hypotheses.
      Participants were evaluated consecutively at our institution from March 2004
      through August 2005.One hundred forty-eight individuals were enrolled, including
      72 patients with TEH and 76 individuals without TEH but with alternative
      diagnoses, such as a screening colonoscopy or colonic polyps. Out of 38 possible
      aetiologic factors evaluated, 20 showed no significant bivariate correlation to
      TEH and were no longer traced, and 16 factors showed a significant bivariate
      relationship to TEH. By multivariate analysis, six independent variables were
      found to predict TEH correctly in 79.1% of cases: age of 46 years or younger, use
      of excessive physical effort, and use of dry toilet paper combined with wet
      cleaning methods after defaecation were associated with a significantly higher
      risk of developing TEH; use of bathtub, use of the shower, and genital cleaning
      before sleep at least once a week were associated with a significantly lower risk
      of developing TEH. CONCLUSION: Six hypotheses on the causes of TEH have a high
      probability of being correct and should be considered in future studies on
      aetiology, prophylaxis, and therapy of TEH.

PMID- 19852814
TI  - Treatment of retained placenta with misoprostol: a randomised controlled trial in
      a low-resource setting (Tanzania).
AB  - BACKGROUND: Retained placenta is one of the common causes of maternal mortality
      in developing countries where access to appropriate obstetrical care is limited.
      Current treatment of retained placenta is manual removal of the placenta under
      anaesthesia, which can only take place in larger health care facilities. Medical
      treatment of retained placenta with prostaglandins E1 (misoprostol) could be cost
      effective and easy-to-use and could be a life-saving option in many low-resource
      settings. The aim of this study is to assess the efficacy and safety of
      sublingually administered misoprostol in women with retained placenta in a low
      resource setting. METHODS:  DESIGN: Multicentered randomised, double-blind,
      placebo-controlled trial, to be conducted in 5 hospitals in Tanzania, Africa.
      INCLUSION CRITERIA: Women with retained placenta, at a gestational age of 28
      weeks or more and blood loss less than 750 ml, 30 minutes after delivery of the
      newborn despite active management of third stage of labour. Trial Entry &
      Randomisation & Study Medication: After obtaining informed consent, eligible
      women will be allocated randomly to the treatment groups using numbered envelopes
      that will be randomized in variable blocks containing identical capsules with
      either 800 microgram of misoprostol or placebo. The drugs will be given
      sublingually. The women, maternal care providers and researchers will be blinded
      to treatment allocation. SAMPLE SIZE: 117 women, to show a 40% reduction in
      manual removals of the placenta (p = 0.05, 80% power). The randomization will be
      misoprostol: placebo = 2:1. PRIMARY STUDY OUTCOME: Expulsion of the placenta
      without manual removal. Secondary outcome is the number of blood transfusions.
      DISCUSSION: This is a protocol for a randomized trial in a low resource setting
      to assess if medical treatment of women with retained placenta with misoprostol
      reduces the incidence of manual removal of the placenta. CLINICAL TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN16104753.

PMID- 19852816
TI  - Drosophila KDM2 is a H3K4me3 demethylase regulating nucleolar organization.
AB  - BACKGROUND: CG11033 (dKDM2) is the Drosophila homolog of the gene KDM2B. dKDM2
      has been known to possess histone lysine demethylase activity towards H3K36me2 in
      cell lines and it regulates H2A ubiquitination. The human homolog of the gene has
      dual activity towards H3K36me2 as well as H3K4me3, and plays an important role in
      cellular senescence. FINDINGS: We have used transgenic flies bearing an RNAi
      construct for the dKDM2 gene. The knockdown of dKDM2 gene was performed by
      crossing UAS-RNAi-dKDM2 flies with actin-Gal4 flies. Western blots of acid
      extracted histones and immunofluoresence analysis of polytene chromosome showed
      the activity of the enzyme dKDM2 to be specific for H3K4me3 in adult flies.
      Immunofluoresence analysis of polytene chromosome also revealed the presence of
      multiple nucleoli in RNAi knockdown mutants of dKDM2 and decreased H3-acetylation
      marks associated with active transcription. CONCLUSION: Our findings indicate
      that dKDM2 is a histone lysine demethylase with specificity for H3K4me3 and
      regulates nucleolar organization.

PMID- 19852815
TI  - A new procedure for determining the genetic basis of a physiological process in a
      non-model species, illustrated by cold induced angiogenesis in the carp.
AB  - BACKGROUND: Physiological processes occur in many species for which there is yet
      no sequenced genome and for which we would like to identify the genetic basis.
      For example, some species increase their vascular network to minimise the effects
      of reduced oxygen diffusion and increased blood viscosity associated with low
      temperatures. Since many angiogenic and endothelial genes have been discovered in
      man, functional homolog relationships between carp, zebrafish and human were used
      to predict the genetic basis of cold-induced angiogenesis in Cyprinus Carpio
      (carp). In this work, carp sequences were collected and built into contigs. Human
      carp functional homolog relationships were derived via zebrafish using a new
      Conditional Stepped Reciprocal Best Hit (CSRBH) protocol. Data sources including
      publications, Gene Ontology and cDNA libraries were then used to predict the
      identity of known or potential angiogenic genes. Finally, re-analyses of cold
      carp microarray data identified carp genes up-regulated in response to low
      temperatures in heart and muscle. RESULTS: The CSRBH approach outperformed all
      other methods and attained 8,726 carp to human functional homolog relationships
      for 16,650 contiguous sequences. This represented 3,762 non-redundant genes and
      908 of them were predicted to have a role in angiogenesis. The total number of up
      regulated differentially expressed genes was 698 and 171 of them were putatively
      angiogenic. Of these, 5 genes representing the functional homologs NCL, RHOA,
      MMP9, GRN and MAPK1 are angiogenesis-related genes expressed in response to low
      temperature. CONCLUSION: We show that CSRBH functional homologs relationships and
      re-analyses of gene expression data can be combined in a non-model species to
      predict genes of biological interest before a genome sequence is fully available.
      Programs to run these analyses locally are available from
      http://www.cbrg.ox.ac.uk/~jherbert/.

PMID- 19852817
TI  - Pathogenesis of aerosolized Eastern Equine Encephalitis virus infection in guinea
      pigs.
AB  - Mice and guinea pigs were experimentally exposed to aerosols containing
      regionally-distinct strains (NJ1959 or ArgM) of eastern equine encephalitis virus
      (EEEV) at two exclusive particle size distributions. Mice were more susceptible
      to either strain of aerosolized EEEV than were guinea pigs; however, clinical
      signs indicating encephalitis were more readily observed in the guinea pigs.
      Lower lethality was observed in both species when EEEV was presented at the
      larger aerosol distribution (> 6 mum), although the differences in the median
      lethal dose (LD50) were not significant. Virus isolation and immunohistochemistry
      indicated that virus invaded the brains of guinea pigs within one day
      postexposure, regardless of viral strain or particle size distribution.
      Immunohistochemistry further demonstrated that neuroinvasion occurred through the
      olfactory system, followed by transneuronal spread to all regions of the brain.
      Olfactory bipolar neurons and neurons throughout the brain were the key viral
      targets. The main microscopic lesions in infected guinea pigs were neuronal
      necrosis, inflammation of the meninges and neuropil of the brain, and vasculitis
      in the brain. These results indicate that guinea pigs experimentally infected by
      aerosolized EEEV recapitulate several key features of fatal human infection and
      thus should serve as a suitable animal model for aerosol exposure to EEEV.

PMID- 19852818
TI  - Association of APOE polymorphism with chronic kidney disease in a nationally
      representative sample: a Third National Health and Nutrition Examination Survey
      (NHANES III) Genetic Study.
AB  - BACKGROUND: Apolipoprotein E polymorphisms (APOE) have been associated with
      lowered glomerular filtration rate (GFR) and chronic kidney disease (CKD) with e2
      allele conferring risk and e4 providing protection. However, few data are
      available in non-European ethnic groups or in a population-based cohort. METHODS:
      The authors analyzed 5,583 individuals from the Third National Health and
      Nutrition Examination Survey (NHANES III) to determine association with estimated
      GFR by the Modification of Diet in Renal Disease (MDRD) equation and low-GFR
      cases. Low-GFR cases were defined as GFR <75 ml/min/1.73 m2; additionally, GFR
      was analyzed continuously. RESULTS: In univariate analysis, the e4 allele was
      negatively associated with low-GFR cases in non-Hispanic whites, odds ratio (OR):
      0.76, 95% confidence interval (CI): 0.60, 0.97. In whites, there was a
      significant association between increasing APOE score (indicating greater number
      of e2 alleles) and higher prevalence of low-GFR cases (OR: 1.21, 95%CI: 1.01,
      1.45). Analysis of continuous GFR in whites found the e4 allele was associated
      with higher levels of continuous GFR (beta-coefficient: 2.57 ml/min/1.73 m2,
      95%CI: 0.005, 5.14); in non-Hispanic blacks the e2 allele was associated with
      lower levels of continuous GFR (beta-coefficient: -3.73 ml/min/1.73 m2, 95%CI: 
      6.61, -0.84). APOE e2 and e4 alleles were rare and not associated with low-GFR
      cases or continuous GFR in Mexican Americans. CONCLUSION: In conclusion, the
      authors observed a weak association between the APOE e4 allele and low-GFR cases
      and continuous GFR in non-Hispanic whites, and the APOE e2 allele and continuous
      GFR in non-Hispanic blacks, but found no association with either measure of
      kidney function in Mexican Americans. Larger studies including multiethnic groups
      are needed to determine the significance of this association.

PMID- 19852819
TI  - Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of
      endogenous interferon-gamma and IL-4.
AB  - INTRODUCTION: Interleukin (IL)-17 plays an important role in the pathogenesis of
      rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA).
      Interferon(IFN)-gamma and IL-4 have been shown to suppress Th17 development in
      vitro, but their potential immunoregulatory roles in vivo are uncertain. The
      goals of this study were to determine the relationship between Th17 responses and
      disease severity in CIA and to assess regulation of IL-17 by endogenous IFN-gamma
      and IL-4. METHODS: DBA1/LacJ mice were immunized with type II collagen in
      complete Freund's adjuvant (CFA) to induce arthritis, and treated with
      neutralizing antibody to IFN-gamma and/or IL-4. Systemic IL-17, IFN-gamma, and IL
      4 were measured in serum. At the peak of disease, cytokine production was
      measured by ELISA of supernatants from spleen, lymph node and paw cultures. Paws
      were also scored for histologic severity of arthritis. RESULTS: Joint
      inflammation was associated with a higher ratio of systemic IL-17/IFN-gamma.
      Neutralization of IFN-gamma accelerated the course of CIA and was associated with
      increased IL-17 levels in the serum and joints. The IFN-gamma/IL-4/IL-17
      responses in the lymphoid organ were distinct from such responses in the joints.
      Neutralization of IL-4 led to increased arthritis only in the absence of IFN
      gamma and was associated with increased bone and cartilage damage without an
      increase in the levels of IL-17. CONCLUSIONS: IL-4 and IFN-gamma both play
      protective roles in CIA, but through different mechanisms. Our data suggests that
      the absolute level of IL-17 is not the only determinant of joint inflammation.
      Instead, the balance of Th1, Th2 and Th17 cytokines control the immune events
      leading to joint inflammation.

PMID- 19852820
TI  - Myocardium tissue changes caused by electrical transthoracic discharges in rats.
AB  - BACKGROUND: Cardiomyocytes cytoarchitecture changes caused by transthoracic
      countershocks have been focused recently. We aimed to evaluate the effects of
      electrical discharge application in the mitochondria structure in atrial
      myocardium of rats. METHODS: An electrical cardioverter was adapted to small
      rodent animals for our research. Electrical discharges were applied to the
      precordial region of 30 albino rats: (1) control group - animals that remained on
      resting period and were afterwards sacrificed; (2) electrical discharge group -
      animals that remained on resting period, followed by ten electrical discharges of
      300 mV and sacrificed, and; (3) electrical post-discharge group - animals that
      remained on a resting period and received ten electrical discharges like the
      electrical discharge group, but were sacrificed seven days subsequently. We
      examined liver, adrenal and left atrium tissue fragments of the three groups.
      RESULTS: It was observed in control and post-discharge groups a normal cellular
      structure aspect with preserved architecture of cardiomyocytes and continuous
      sarcoplasmic membrane integrity. On the other hand, cardiac muscle fibers with
      mitochondrial edema and lysis occurred in the discharge group. Glycogen and
      adrenal lipids were not depleted in all groups. CONCLUSION: These data suggest
      that transthoracic electrical discharges induce mitochondrial injuries in atrial
      cardiac cells of rats.

PMID- 19852821
TI  - Impact on allergic immune response after treatment with vitamin A.
AB  - BACKGROUND: Vitamin A may have some influence on the immune system, but the role
      in allergy modulation is still unclear. OBJECTIVE: To clarify whether high levels
      of retinoic acid (RA) affects allergic response in vivo, we used a murine
      experimental model of airway allergic disease. METHODS: Ovalbumin (OVA)
      immunization/OVA-challenge (OVA/OVA) and house dust mite (HDM)-immunization/HDM
      challenge (HDM/HDM) experimental murine models of allergic airway disease, using
      C57Bl.10/Q groups of mice (n = 10) treated subcutaneously with different
      concentrations of all-trans RA (0, 50, 500 and 2,500 ug) every 2-days were used
      to assess the allergic immune response. RESULTS: Levels of total and specific-IgE
      in sera were increased in all groups of RA treated OVA/OVA and HDM/HDM mice.
      Percentage and total amount of recruited eosinophil in airways by bronchoalveolar
      lavage fluid (BALF) were significantly enhanced in groups treated with 50, 500
      and 2,500 ug of RA compared to non-treated mice. However, the group of mice
      treated with 2,500 ug had less eosinophil recruitment than the other two groups
      (50 and 500 ug). In parallel, levels of IL-5 and total IgE in BALF were also
      significantly diminished in the group treated with 2,500 ug compared to the other
      2 groups (50 and 500 ug). Finally, total lung resistance was decreased in group
      treated with 2,500 ug compared to non-treated mice. CONCLUSION: Our results
      suggest that retinoic acid directly enhances allergic response in vivo, but in
      higher doses may produce of immune suppression.

PMID- 19852822
TI  - Liposarcoma of the colon presenting as an endoluminal mass.
AB  - BACKGROUND: Liposarcoma is one of the most common soft tissue sarcoma of adult
      life, usually occurring in the retroperitoneum and the extremities. Primary
      liposarcoma of the colon is very rare. The optimal treatment has not been
      established due to the small number of cases reported. We report a case of
      primary liposarcoma of the colon presenting as a massive intraluminal lesion.
      CASE PRESENTATION: A 79-year-old woman presented with abdominal pain, progressive
      constipation and weight loss. A CT scan and a colonoscopy revealed an
      intraluminal mass in the transverse colon and multiple intraperitoneal lesions.
      The patient underwent surgical resection of the lesions. Pathologic examination
      was consistent with pleomorphic liposarcoma of the colon. CONCLUSION: Although no
      guidelines are available for the management of liposarcoma of the colon, surgical
      resection should be performed when feasible. Our patient's overall survival was
      satisfactory in spite of the multiple negative prognostic factors.

PMID- 19852823
TI  - Whole-genome analysis of pseudorabies virus gene expression by real-time
      quantitative RT-PCR assay.
AB  - BACKGROUND: Pseudorabies virus (PRV), a neurotropic herpesvirus of pigs, serves
      as an excellent model system with which to investigate the herpesvirus life cycle
      both in cultured cells and in vivo. Real-time RT-PCR is a very sensitive,
      accurate and reproducible technique that can be used to detect very small amounts
      of RNA molecules, and it can therefore be applied for analysis of the expression
      of herpesvirus genes from the very early period of infection. RESULTS: In this
      study, we have developed and applied a quantitative reverse transcriptase-based
      real-time PCR technique in order to profile transcription from the whole genome
      of PRV after lytic infection in porcine kidney cells. We calculated the relative
      expression ratios in a novel way, which allowed us to compare different PRV genes
      with respect to their expression dynamics, and to divide the PRV genes into
      distinct kinetic classes. This is the first publication on the whole-genome
      analysis of the gene expression of an alpha-herpesvirus by qRT2-PCR. We
      additionally established the kinetic properties of uncharacterized PRV genes and
      revised or confirmed data on PRV genes earlier examined by traditional methods
      such as Northern blot analysis. Our investigations revealed that genes with the
      same expression properties form clusters on the PRV genome: nested overlapping
      genes belong in the same kinetic class, while most convergent genes belong in
      different kinetic classes. Further, we detected inverse relationships as concerns
      the expressions of EP0 and IE180 mRNAs and their antisense partners. CONCLUSION:
      Most (if not all) PRV genes begin to be expressed from the onset of viral
      expression. No sharp boundary was found between the groups of early and late
      genes classified on the basis of their requirement for viral DNA synthesis. The
      expressions of the PRV genes were analyzed, categorized and compared by qRT2-PCR
      assay, with the average of the minimum cycle threshold used as a control for the
      calculation of a particular R value. In principle, this new calculation technique
      is applicable for the analysis of gene expression in all temporally changing
      genetic systems.

PMID- 19852824
TI  - CD44 expression positively correlates with Foxp3 expression and suppressive
      function of CD4+ Treg cells.
AB  - BACKGROUND: CD4(+)CD25(+) regulatory T (T(reg)) cells develop in the thymus and
      can suppress T cell proliferation, modulated by Foxp3 and cytokines; however, the
      relevance of CD44 in T(reg) cell development is less clear. To address this
      issue, we analyzed Foxp3 expression in CD44(+) T(reg) cells by using multiple
      parameters, measured the levels of the immunoregulatory cytokine interleukin (IL)
      10 in various thymocyte subsets, and determined the suppressor activity in
      different splenic T(reg) cell populations. RESULTS: Within mouse thymocytes, we
      detected T(reg) cells with two novel phenotypes, namely the CD4(+)CD8(
      )CD25(+)CD44(+) and CD4(+)CD8(-)CD25(+)CD44(-)staining features. Additional multi
      parameter analyses at the single-cell and molecular levels suggested to us that
      CD44 expression positively correlated with Foxp3 expression in thymocytes, the
      production of IL-10, and T(reg) activity in splenic CD4(+)CD25(+) T cells. This
      suppressive effect of T(reg) cells on T cell proliferation could be blocked by
      using anti-IL-10 neutralizing antibodies. In addition, CD4(+)CD25(+)CD44(+)
      T(reg) cells expressed higher levels of IL-10 and were more potent in suppressing
      effector T cell proliferation than were CD4(+)CD25(+)CD44(-) cells. CONCLUSION:
      This study indicates the presence of two novel phenotypes of T(reg) cells in the
      thymus, the functional relevance of CD44 in defining T(reg) cell subsets, and the
      role of both IL-10 and Foxp3 in modulating the function of T(reg) cells.
      REVIEWERS: This article was reviewed by Dr. M. Lenardo, Dr. L. Klein & G.
      Wirnsberger (nominated by Dr. JC Zungia-Pfluker), and Dr. E.M. Shevach.

PMID- 19852825
TI  - Evaluation of errors and limits of the 63-microuse-dust-fraction method, a
      surrogate to predict hidden moisture damage.
AB  - BACKGROUND: The aim of this study is to analyze possible random and systematic
      measurement errors and to detect methodological limits of the previously
      established method. FINDINGS: To examine the distribution of random errors
      (repeatability standard deviation) of the detection procedure, collective samples
      were taken from two uncontaminated rooms using a sampling vacuum cleaner, and 10
      sub-samples each were examined with 3 parallel cultivation plates (DG18). In this
      two collective samples of new dust, the total counts of Aspergillus spp. varied
      moderately by 25 and 29% (both 9 cfu per plate). At an average of 28 cfu/plate,
      the total number varied only by 13%.For the evaluation of the influence of old
      dust, old and fresh dust samples were examined. In both cases with old dust, the
      old dust influenced the results indicating false positive results, where hidden
      moist was indicated but was not present. To quantify the influence of sand and
      sieving, 13 sites were sampled in parallel using the 63-mum- and total dust
      collection approaches. Sieving to 63-mum resulted in a more then 10-fold
      enrichment, due to the different quantity of inert sand in each total dust
      sample. CONCLUSION: The major errors during the quantitative evaluation from
      house dust samples for mould fungi as reference values for assessment resulted
      from missing filtration, contamination with old dust and the massive influence of
      soil. If the assessment is guided by indicator genera, the percentage standard
      deviation lies in a moderate range.

PMID- 19852826
TI  - Traditional eye medicine use by newly presenting ophthalmic patients to a
      teaching hospital in south-eastern Nigeria: socio-demographic and clinical
      correlates.
AB  - BACKGROUND: This study set out to determine the incidence, socio-demographic, and
      clinical correlates of Traditional Eye Medicine (TEM) use in a population of
      newly presenting ophthalmic outpatients attending a tertiary eye care centre in
      south-eastern Nigeria. METHODS: In a comparative cross-sectional survey at the
      eye clinic of the University of Nigeria Teaching Hospital (UNTH), Enugu, between
      August 2004 - July 2006, all newly presenting ophthalmic outpatients were
      recruited. Participants' socio-demographic and clinical data and profile of TEM
      use were obtained from history and examination of each participant and entered
      into a pretested questionnaire and proforma. Participants were subsequently
      categorized into TEM- users and non-users; intra-group analysis yielded
      proportions, frequencies, and percentages while chi-square test was used for
      inter-group comparisons at P = 0.01, df = 1. RESULTS: Of the 2,542 (males, 48.1%;
      females, 51.9%) participants, 149 (5.9%) (males, 45%; females, 55%) used TEM for
      their current eye disease. The TEMs used were chemical substances (57.7%), plant
      products (37.7%), and animal products (4.7%). They were more often prescribed by
      non-traditional (66.4%) than traditional (36.9%) medicine practitioners. TEMs
      were used on account of vision loss (58.5%), ocular itching (25.4%) and eye
      discharge (3.8%). Reported efficacy from previous users (67.1%) and belief in
      potency (28.2%) were the main reasons for using TEM. Civil servants (20.1%),
      farmers (17.7%), and traders (14.1%) were the leading users of TEM. TEM use was
      significantly associated with younger age (p < 0.01), being married (p < 0.01),
      rural residence (p < 0.01), ocular anterior segment disease (p < 0.01), delayed
      presentation (p < 0.01), low presenting visual acuity (p < 0.01), and co-morbid
      chronic medical disease (p < 0.01), but not with gender (p = 0.157), and
      educational status (p = 0.115). CONCLUSION: The incidence of TEM use among new
      ophthalmic outpatients at UNTH is low. The reasons for TEM use are amenable to
      positive change through enhanced delivery of promotive, preventive, and curative
      public eye care services. This has implications for eye care planners and
      implementers. To reverse the trend, we suggest strengthening of eye care
      programmes, even distribution of eye care resources, active collaboration with
      orthodox eye care providers and traditional medical practitioners, and
      intensification of research efforts into the pharmacology of TEMs.

PMID- 19852828
TI  - Can economic evaluation in telemedicine be trusted? A systematic review of the
      literature.
AB  - BACKGROUND: Telemedicine has been advocated as an effective means to provide
      health care services over a distance. Systematic information on costs and
      consequences has been called for to support decision-making in this field. This
      paper provides a review of the quality, validity and generalisability of economic
      evaluations in telemedicine. METHODS: A systematic literature search in all
      relevant databases was conducted and forms the basis for addressing these issues.
      Only articles published in peer-reviewed journals and written in English in the
      period from 1990 to 2007 were analysed. The literature search identified 33
      economic evaluations where both costs (resource use) and outcomes (non-resource
      consequences) were measured. RESULTS: This review shows that economic evaluations
      in telemedicine are highly diverse in terms of both the study context and the
      methods applied. The articles covered several medical specialities ranging from
      cardiology and dermatology to psychiatry. The studies analysed telemedicine in
      home care, and in primary and secondary care settings using a variety of
      different technologies including videoconferencing, still-images and monitoring
      (store-and-forward telemedicine). Most studies used multiple outcome measures and
      analysed the effects using disaggregated cost-consequence frameworks. Objectives,
      study design, and choice of comparators were mostly well reported. The majority
      of the studies lacked information on perspective and costing method, few used
      general statistics and sensitivity analysis to assess validity, and even fewer
      used marginal analysis. CONCLUSION: As this paper demonstrates, the majority of
      the economic evaluations reviewed were not in accordance with standard evaluation
      techniques. Further research is needed to explore the reasons for this and to
      address how economic evaluation in telemedicine best can take advantage of local
      constraints and at the same time produce valid and generalisable results.

PMID- 19852827
TI  - Selenium deficiency impairs host innate immune response and induces
      susceptibility to Listeria monocytogenes infection.
AB  - BACKGROUND: Susceptibility or resistance to infection with Listeria monocytogenes
      correlates with Selenium (Se) deficiency in response to infection. RESULTS: Se
      deficient mouse models of listeriosis were used to study the innate immune
      response during the course of L. monocytogenes infection. Blood samples from
      mouse models were used for Se status. The concentration of MDA, SOD, GPx and CAT
      in blood has revealed that lower Se level exist in Se-deficient mice. Intestine,
      mesenteric lymph node, liver, spleen and brain from each mouse were to study the
      bacterial burden in organs. The analysis of cell types of spleen from Se
      deficient mice revealed that the ability of the host to elicit a rapid
      recruitment and activation of systemic innate immune response to infection was to
      a certain extent compromised under conditions of Se deficiency. The cytokine
      levels in the serum and cytokine expression levels in the livers from Se
      deficient mice revealed that the innate immune response of Se-deficient mice was
      impaired throughout the course of infection. These results suggest that innate
      immune response is altered by Se deficiency after infection with L.
      monocytogenes. CONCLUSION: In conclusion, induced susceptibility of host
      resistance is associated with an impaired innate immune response following
      infection with L. monocytogenes in C57BL/6 Se-deficient mice.

PMID- 19852829
TI  - Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine
      for malaria prophylaxis in children with sickle cell anaemia in Uganda: a
      randomized controlled trial.
AB  - BACKGROUND: Malaria carries high case fatality among children with sickle cell
      anaemia. In Uganda, chloroquine is used for prophylaxis in these children despite
      unacceptably high levels of resistance. Intermittent presumptive treatment with
      sulphadoxine-pyrimethamine (SP) has shown great potential for reducing prevalence
      of malaria and anaemia among pregnant women and infants. OBJECTIVE: To compare
      the efficacy of monthly SP presumptive treatment, versus weekly chloroquine for
      malaria prophylaxis in children attending the Sickle Cell Clinic, Mulago
      Hospital. METHODS: Two hundred and forty two children with sickle cell anaemia
      were randomized to presumptive treatment with SP or weekly chloroquine for
      malaria prophylaxis. Active detection of malaria was made at each weekly visit to
      the clinic over one month. The primary outcome measure was the proportion of
      children with one malaria episode at one month follow-up. The secondary outcome
      measures included malaria-related admissions and adverse effects of the drugs.
      RESULTS: Ninety-three percent (114/122) of the children in the chloroquine group
      and 94% (113/120) in the SP group completed one month follow up. SP reduced
      prevalence of malaria by 50% compared to chloroquine [OR = 0.50, (95% CI 0.26
      0.97)]; p = 0.042. Six percent (7/122) of the children receiving weekly
      chloroquine had malaria related admissions compared to 2.5% (3/120) on
      presumptive treatment with SP. No serious drug effects were reported in both
      treatment groups CONCLUSION: Presumptive treatment with SP was more efficacious
      than weekly chloroquine in reducing prevalence of malaria in children with sickle
      cell anaemia. Continued use of chloroquine for malaria chemoprophylaxis in
      children with sickle cell anaemia in Uganda does not seem to be justified.

PMID- 19852830
TI  - Financial access to health care in Karuzi, Burundi: a household-survey based
      performance evaluation.
AB  - BACKGROUND: In 2003, Medecins Sans Frontieres, the provincial government, and the
      provincial health authority began a community project to guarantee financial
      access to primary health care in Karuzi province, Burundi. The project used a
      community-based assessment to provide exemption cards for indigent households and
      a reduced flat fee for consultations for all other households. METHODS: An
      evaluation was carried out in 2005 to assess the impact of this project. Primary
      data collection was through a cross-sectional household survey of the catchment
      areas of 10 public health centres. A questionnaire was used to determine the
      accuracy of the community-identification method, households' access to health
      care, and costs of care. Household socioeconomic status was determined by
      reported expenditures and access to land. RESULTS: Financial access to care at
      the nearest health centre was ensured for 70% of the population. Of the remaining
      30%, half experienced financial barriers to access and the other half chose
      alternative sites of care. The community-based assessment increased the number of
      people of the population who qualified for fee exemptions to 8.6% but many people
      who met the indigent criteria did not receive a card. Eighty-eight percent of the
      population lived under the poverty threshold. Referring to the last sickness
      episode, 87% of households reported having no money available and 25% risked
      further impoverishment because of healthcare costs even with the financial
      support system in place. CONCLUSION: The flat fee policy was found to reduce cost
      barriers for some households but, given the generalized poverty in the area, the
      fee still posed a significant financial burden. This report showed the limits of
      a programme of fee exemption for indigent households and a flat fee for others in
      a context of widespread poverty.

PMID- 19852831
TI  - Co-transfection of plasmid DNA and laser-generated gold nanoparticles does not
      disturb the bioactivity of GFP-HMGB1 fusion protein.
AB  - Ultrashort pulsed laser ablation in liquids represents a powerful tool for the
      generation of pure gold nanoparticles (AuNPs) avoiding chemical precursors and
      thereby making them especially interesting for biomedical applications. However,
      because of their electron accepting properties, laser-generated AuNPs might
      affect biochemical properties of biomolecules, which often adsorb onto the
      nanoparticles. We investigated possible effects of such laser-generated AuNPs on
      biological functionality of DNA molecules. We tested four differently sized and
      positively charged AuNPs by incubating them with recombinant eGFP-C1-HMGB1 DNA
      expression plasmids that code for eGFP fusion proteins and contain the canine
      architectural transcription factor HMGB1. We were able to show that successfully
      transfected mammalian cells are still able to synthesize and process the fusion
      proteins. Our observations revealed that incubation of AuNP with the plasmid DNA
      encoding the recombinant canine HMGB1 neither prevented the mediated uptake of
      the vector through the plasma membrane in presence of a transfection reagent nor
      had any effect on the transport of the synthesized fusion proteins to the nuclei.
      Biological activity of the recombinant GFP-HMGB1 fusion protein appears to have
      not been affected either, as a strong characteristic protein accumulation in the
      nucleus could be observed. We also discovered that transfection efficiencies
      depend on the size of AuNP. In conclusion, our data indicate that laser-generated
      AuNPs present a good alternative to chemically synthesized nanoparticles for use
      in biomedical applications.

PMID- 19852832
TI  - Using theories of behaviour to understand transfusion prescribing in three
      clinical contexts in two countries: development work for an implementation trial.
AB  - BACKGROUND: Blood transfusion is an essential part of healthcare and can improve
      patient outcomes. However, like most therapies, it is also associated with
      significant clinical risks. In addition, there is some evidence of overuse.
      Understanding the potential barriers and enablers to reduced prescribing of blood
      products will facilitate the selection of intervention components likely to be
      effective, thereby reducing the number of costly trials evaluating different
      implementation strategies. Using a theoretical basis to understand behaviours
      targeted for change will contribute to a 'basic science' relating to determinants
      of professional behaviour and how these inform the selection of techniques for
      changing behaviour. However, it is not clear which theories of behaviour are
      relevant to clinicians' transfusing behaviour. The aim of this study is to use a
      theoretical domains framework to identify relevant theories, and to use these
      theories to identify factors that predict the decision to transfuse. METHODS: The
      study involves two steps: interview study and questionnaire study. Using a
      previously identified framework, we will conduct semi-structured interviews with
      clinicians to elicit their views about which factors are associated with waiting
      and further monitoring the patient rather than transfusing red blood cells.
      Interviews will cover the following theoretical domains: knowledge; skills;
      social/professional role and identity; beliefs about capabilities; beliefs about
      consequences; motivation and goals; memory, attention, and decision processes;
      environmental context and resources; social influences; emotion; behavioural
      regulation; nature of the behaviour. The interviews will take place independently
      in Canada and the UK and involve two groups of physicians in each country (UK:
      adult and neonatal intensive care physicians; Canada: intensive care physicians
      and orthopaedic surgeons). We will: analyse interview transcript content to
      select relevant theoretical domains; use consensus processes to map these domains
      on to theories of behaviour; develop questionnaires based on these theories; and
      mail them to each group of physicians in the two countries. From our previous
      work, it is likely that the theories will include: theory of planned behaviour,
      social cognitive theory and the evidence-based strategy, implementation
      intention. The questionnaire data will measure predictor variables (theoretical
      constructs) and outcome variables (intention and clinical decision), and will be
      analysed using multiple regression analysis. We aim to achieve 150 respondents in
      each of the four groups for each postal survey.

PMID- 19852833
TI  - Maintaining over time clinical performance targets on anaemia correction in
      unselected population on chronic dialysis at 20 Italian centres. Data from a
      retrospective study for a clinical audit.
AB  - BACKGROUND: The Italian and European Best Practice Guidelines (EBPG) recommend a
      target haemoglobin value greater than 11 g/dl in most patients with Chronic
      Kidney Diseases. However, it is still difficult to maintain these values at a
      steady rate. Thus, the main aim of the study was to evaluate, throughout 2005,
      how many patients steadily maintained the performance targets related to anaemia
      treatment. METHODS: The survey was conducted on 3283 patients on haemodialysis
      (HD) and peritoneal dialysis (PD) at 20 Italian dialysis centres. 540 patients
      were randomly selected; each centre provided a statistically significant sample
      proportional to its total number of patients. Maintenance of the following target
      levels was assessed over time: Haemoglobin (HB) 11-12 gr/dl; Iron: 60-160 mcg/dl;
      Ferritin: 30-400 mcg/l; Transferrin: 200-360 mg/dl; Transferrin saturation
      percentage (TSAT %):> 25 <50; Dialysis doses (KT/V): >1.2 <2.0 for non-diabetic
      HD patients; >1.5 <2.2 for diabetic HD patients; DP: >1.8 <2.5.Outcome included:1
      Percentage of target maintenance for each parameter.2- Erythropoietin dose in
      relation to dialysis techniques, presence of cancer or myeloma, diabetic status,
      Vitamin B therapy.3- Erythropoietin dose (International Units/kg/week) (IU/kg/wk)
      depending on: haemoglobin values, hospitalization of more than 3 days. RESULTS:
      Mean age was 65.1; mean haemoglobin concentration over the whole population was
      11.3 gr/dl (Standard Deviation (SD): 0.91). The clinical performance targets were
      maintained over time as follows: HB: 4.3% (Mean 11.43 gr/dl) (SD: 0.42);
      Ferritin: 71.1% (Mean: 250.23 mcg/L (SD:104.07); Iron: 95.0% (Mean 59.79
      mcg/dl)(SD:16.76); Transferrin: 44.8% (Mean 216.83 mg/dl) (SD: 19,50); TSAT %: in
      8.4% (Mean: 34.33% (SD: 6.56); HD KT/V: 61.0% (Mean:1.46) (SD: 0.7); PD
      KT/V:31.4% (Mean: 2.10) (SD: 0.02). The average weekly dose of Erythropoietin
      (IU/Kg/Wk) was significantly lower for the peritoneal dialysis technique; the
      higher haemoglobin values, the lower the Erythropoietin dose (IU/Kg/Wk).
      CONCLUSION: A very low percentage of patients maintained haemoglobin target
      values over time. We need to identify precise criteria to evaluate the stability
      over time of clinical performance targets proposed by the guidelines.

PMID- 19852834
TI  - Accountable priority setting for trust in health systems--the need for research
      into a new approach for strengthening sustainable health action in developing
      countries.
AB  - Despite multiple efforts to strengthen health systems in low and middle income
      countries, intended sustainable improvements in health outcomes have not been
      shown. To date most priority setting initiatives in health systems have mainly
      focused on technical approaches involving information derived from burden of
      disease statistics, cost effectiveness analysis, and published clinical trials.
      However, priority setting involves value-laden choices and these technical
      approaches do not equip decision-makers to address a broader range of relevant
      values - such as trust, equity, accountability and fairness - that are of concern
      to other partners and, not least, the populations concerned. A new focus for
      priority setting is needed.Accountability for Reasonableness (AFR) is an explicit
      ethical framework for legitimate and fair priority setting that provides guidance
      for decision-makers who must identify and consider the full range of relevant
      values. AFR consists of four conditions: i) relevance to the local setting,
      decided by agreed criteria; ii) publicizing priority-setting decisions and the
      reasons behind them; iii) the establishment of revisions/appeal mechanisms for
      challenging and revising decisions; iv) the provision of leadership to ensure
      that the first three conditions are met.REACT - "REsponse to ACcountable priority
      setting for Trust in health systems" is an EU-funded five-year intervention study
      started in 2006, which is testing the application and effects of the AFR approach
      in one district each in Kenya, Tanzania and Zambia. The objectives of REACT are
      to describe and evaluate district-level priority setting, to develop and
      implement improvement strategies guided by AFR and to measure their effect on
      quality, equity and trust indicators. Effects are monitored within selected
      disease and programme interventions and services and within human resources and
      health systems management. Qualitative and quantitative methods are being applied
      in an action research framework to examine the potential of AFR to support
      sustainable improvements to health systems performance.This paper reports on the
      project design and progress and argues that there is a high need for research
      into legitimate and fair priority setting to improve the knowledge base for
      achieving sustainable improvements in health outcomes.

PMID- 19852835
TI  - Expulsion of Trichuris muris is associated with increased expression of
      angiogenin 4 in the gut and increased acidity of mucins within the goblet cell.
AB  - BACKGROUND: Trichuris muris in the mouse is an invaluable model for infection of
      man with the gastrointestinal nematode Trichuris trichiura. Three T. muris
      isolates have been studied, the Edinburgh (E), the Japan (J) and the Sobreda (S)
      isolates. The S isolate survives to chronicity within the C57BL/6 host whereas E
      and J are expelled prior to reaching fecundity. How the S isolate survives so
      successfully in its host is unclear. RESULTS: Microarray analysis was used as a
      tool to identify genes whose expression could determine the differences in
      expulsion kinetics between the E and S T. muris isolates. Clear differences in
      gene expression profiles were evident as early as day 7 post-infection (p.i.). 43
      probe sets associated with immune and defence responses were up-regulated in gut
      tissue from an E isolate-infected C57BL/6 mouse compared to tissue from an S
      isolate infection, including the message for the anti-microbial protein,
      angiogenin 4 (Ang4). This led to the identification of distinct differences in
      the goblet cell phenotype post-infection with the two isolates. CONCLUSION:
      Differences in gene expression levels identified between the S and E-infected
      mice early during infection have furthered our knowledge of how the S isolate
      persists for longer than the E isolate in the C57BL/6 mouse. Potential new
      targets for manipulation in order to aid expulsion have been identified. Further
      we provide evidence for a potential new marker involving the acidity of the
      mucins within the goblet cell which may predict outcome of infection within days
      of parasite exposure.

PMID- 19852836
TI  - A structure filter for the Eukaryotic Linear Motif Resource.
AB  - BACKGROUND: Many proteins are highly modular, being assembled from globular
      domains and segments of natively disordered polypeptides. Linear motifs, short
      sequence modules functioning independently of protein tertiary structure, are
      most abundant in natively disordered polypeptides but are also found in
      accessible parts of globular domains, such as exposed loops. The prediction of
      novel occurrences of known linear motifs attempts the difficult task of
      distinguishing functional matches from stochastically occurring non-functional
      matches. Although functionality can only be confirmed experimentally, confidence
      in a putative motif is increased if a motif exhibits attributes associated with
      functional instances such as occurrence in the correct taxonomic range, cellular
      compartment, conservation in homologues and accessibility to interacting
      partners. Several tools now use these attributes to classify putative motifs
      based on confidence of functionality. RESULTS: Current methods assessing motif
      accessibility do not consider much of the information available, either
      predicting accessibility from primary sequence or regarding any motif occurring
      in a globular region as low confidence. We present a method considering
      accessibility and secondary structural context derived from experimentally solved
      protein structures to rectify this situation. Putatively functional motif
      occurrences are mapped onto a representative domain, given that a high quality
      reference SCOP domain structure is available for the protein itself or a close
      relative. Candidate motifs can then be scored for solvent-accessibility and
      secondary structure context. The scores are calibrated on a benchmark set of
      experimentally verified motif instances compared with a set of random matches. A
      combined score yields 3-fold enrichment for functional motifs assigned to high
      confidence classifications and 2.5-fold enrichment for random motifs assigned to
      low confidence classifications. The structure filter is implemented as a pipeline
      with both a graphical interface via the ELM resource http://elm.eu.org/ and
      through a Web Service protocol. CONCLUSION: New occurrences of known linear
      motifs require experimental validation as the bioinformatics tools currently have
      limited reliability. The ELM structure filter will aid users assessing candidate
      motifs presenting in globular structural regions. Most importantly, it will help
      users to decide whether to expend their valuable time and resources on
      experimental testing of interesting motif candidates.

PMID- 19852837
TI  - An effectiveness analysis of healthcare systems using a systems theoretic
      approach.
AB  - BACKGROUND: The use of accreditation and quality measurement and reporting to
      improve healthcare quality and patient safety has been widespread across many
      countries. A review of the literature reveals no association between the
      accreditation system and the quality measurement and reporting systems, even when
      hospital compliance with these systems is satisfactory. Improvement of health
      care outcomes needs to be based on an appreciation of the whole system that
      contributes to those outcomes. The research literature currently lacks an
      appropriate analysis and is fragmented among activities. This paper aims to
      propose an integrated research model of these two systems and to demonstrate the
      usefulness of the resulting model for strategic research planning.
      METHODS/DESIGN: To achieve these aims, a systematic integration of the healthcare
      accreditation and quality measurement/reporting systems is structured
      hierarchically. A holistic systems relationship model of the administration
      segment is developed to act as an investigation framework. A literature-based
      empirical study is used to validate the proposed relationships derived from the
      model. Australian experiences are used as evidence for the system effectiveness
      analysis and design base for an adaptive-control study proposal to show the
      usefulness of the system model for guiding strategic research. RESULTS: Three
      basic relationships were revealed and validated from the research literature. The
      systemic weaknesses of the accreditation system and quality measurement/reporting
      system from a system flow perspective were examined. The approach provides a
      system thinking structure to assist the design of quality improvement strategies.
      The proposed model discovers a fourth implicit relationship, a feedback between
      quality performance reporting components and choice of accreditation components
      that is likely to play an important role in health care outcomes. An example
      involving accreditation surveyors is developed that provides a systematic search
      for improving the impact of accreditation on quality of care and hence on the
      accreditation/performance correlation. CONCLUSION: There is clear value in
      developing a theoretical systems approach to achieving quality in health care.
      The introduction of the systematic surveyor-based search for improvements creates
      an adaptive-control system to optimize health care quality. It is hoped that
      these outcomes will stimulate further research in the development of strategic
      planning using systems theoretic approach for the improvement of quality in
      health care.

PMID- 19852838
TI  - Structural insights into the substrate tunnel of Saccharomyces cerevisiae
      carbonic anhydrase Nce103.
AB  - BACKGROUND: The carbonic anhydrases (CAs) are involved in inorganic carbon
      utilization. They have been classified into six evolutionary and structural
      families: alpha-, beta-, gamma-, delta-, epsilon-, zeta- CAs, with beta-CAs
      present in higher plants, algae and prokaryotes. The yeast Saccharomyces
      cerevisiae encodes a single copy of beta-CA Nce103/YNL036W. RESULTS: We
      determined the crystal structure of Nce103 in complex with a substrate analog at
      2.04 A resolution. It assembles as a homodimer, with the active site located at
      the interface between two monomers. At the bottom of the substrate pocket, a zinc
      ion is coordinated by the three highly conserved residues Cys57, His112 and
      Cys115 in addition to a water molecule. Residues Asp59, Arg61, Gly111, Leu102,
      Val80, Phe75 and Phe97 form a tunnel to the bottom of the active site which is
      occupied by a molecule of the substrate analog acetate. Activity assays of full
      length and two truncated versions of Nce103 indicated that the N-terminal arm is
      indispensable. CONCLUSION: The quaternary structure of Nce103 resembles the
      typical plant type beta-CAs of known structure, with an N-terminal arm
      indispensable for the enzymatic activity. Comparative structure analysis enables
      us to draw a possible tunnel for the substrate to access the active site which is
      located at the bottom of a funnel-shaped substrate pocket.

PMID- 19852839
TI  - Computational annotation of genes differentially expressed along olive fruit
      development.
AB  - BACKGROUND: Olea europaea L. is a traditional tree crop of the Mediterranean
      basin with a worldwide economical high impact. Differently from other fruit tree
      species, little is known about the physiological and molecular basis of the olive
      fruit development and a few sequences of genes and gene products are available
      for olive in public databases. This study deals with the identification of large
      sets of differentially expressed genes in developing olive fruits and the
      subsequent computational annotation by means of different software. RESULTS: mRNA
      from fruits of the cv. Leccino sampled at three different stages [i.e., initial
      fruit set (stage 1), completed pit hardening (stage 2) and veraison (stage 3)]
      was used for the identification of differentially expressed genes putatively
      involved in main processes along fruit development. Four subtractive
      hybridization libraries were constructed: forward and reverse between stage 1 and
      2 (libraries A and B), and 2 and 3 (libraries C and D). All sequenced clones
      (1,132 in total) were analyzed through BlastX against non-redundant NCBI
      databases and about 60% of them showed similarity to known proteins. A total of
      89 out of 642 differentially expressed unique sequences was further investigated
      by Real-Time PCR, showing a validation of the SSH results as high as 69%. Library
      specific cDNA repertories were annotated according to the three main vocabularies
      of the gene ontology (GO): cellular component, biological process and molecular
      function. BlastX analysis, GO terms mapping and annotation analysis were
      performed using the Blast2GO software, a research tool designed with the main
      purpose of enabling GO based data mining on sequence sets for which no GO
      annotation is yet available. Bioinformatic analysis pointed out a significantly
      different distribution of the annotated sequences for each GO category, when
      comparing the three fruit developmental stages. The olive fruit-specific
      transcriptome dataset was used to query all known KEGG (Kyoto Encyclopaedia of
      Genes and Genomes) metabolic pathways for characterizing and positioning
      retrieved EST records. The integration of the olive sequence datasets within the
      MapMan platform for microarray analysis allowed the identification of specific
      biosynthetic pathways useful for the definition of key functional categories in
      time course analyses for gene groups. CONCLUSION: The bioinformatic annotation of
      all gene sequences was useful to shed light on metabolic pathways and
      transcriptional aspects related to carbohydrates, fatty acids, secondary
      metabolites, transcription factors and hormones as well as response to biotic and
      abiotic stresses throughout olive drupe development. These results represent a
      first step toward both functional genomics and systems biology research for
      understanding the gene functions and regulatory networks in olive fruit growth
      and ripening.

PMID- 19852840
TI  - Internal sphincterotomy reduces postoperative pain after Milligan Morgan
      haemorrhoidectomy.
AB  - BACKGROUND: Over the last few years, there has been increasing attention on
      surgical procedures to treat haemorrhoids. The Milligan-Morgan haemorrhoidectomy
      is still one of the most popular surgical treatments of haemorrhoids. The aim of
      the present work is to assess postoperative pain, together with other early and
      late complications, after Milligan-Morgan haemorrhoidectomy as we could observe
      in our experience before and after performing an internal sphincterotomy.
      METHODS: from January 1980 to May 2007, we operated 850 patients, but only 699
      patients (median age 53) were included in the present study because they
      satisfied our inclusion criteria. The patients were divided into two groups: all
      the patients operated on before 1995 (group A); all the patients operated on
      after 1995 (group B). Since 1995 an internal sphincterotomy of about 1 cm has
      been performed at the end of the procedure. The data concerning the complications
      of these two groups were compared. All the patients received a check-up at one
      and six months after operation and a telephone questionnaire three years after
      operation to evalue medium and long term results. RESULTS: after one month 507
      patients (72.5%) did not have any postoperative complication. Only 192 patients
      (27.46%) out of 699 presented postoperative complication and the most frequent
      one (23.03%) was pain. The number of patients who suffered from postoperative
      pain decreased significantly when performing internal sphincterotomy, going from
      28.8% down to 10.45% (chi(2): 10,880; p = 0,0001); 95% Confidence Interval (CI)
      24.7 to 28.9 (group A) and 10.17 to 10.72 (group B). In 51 cases (7.29%) urinary
      retention was registered. Six cases of bleeding (0.85%) were registered. Medium
      and long term follow up did not show any difference among the two groups.
      CONCLUSION: internal sphincterotomy: reduces significantly pain only in the first
      postoperative period, but not in the medium-long term follow up; does not
      increase the incidence of continence impairment when performed; does not
      influence the incidence of the other postoperative complications especially as
      regard medium and long term results.

PMID- 19852841
TI  - Acupuncture for pain and osteoarthritis of the knee: a pilot study for an open
      parallel-arm randomised controlled trial.
AB  - BACKGROUND: There is some evidence that acupuncture for pain and osteoarthritis
      (OA) of the knee is more than a placebo, and short term clinical benefits have
      been observed when acupuncture is compared to usual care. However there is
      insufficient evidence on whether clinical benefits of acupuncture are sustained
      over the longer term. In this study our key objectives are to inform the design
      parameters for a fully powered pragmatic randomised controlled trial. These
      objectives include establishing potential recruitment rates, appropriate
      validated outcome measures, attendance levels for acupuncture treatment, loss to
      follow up and the sample size for a full scale trial. METHODS: Potential
      participants aged over 50 with pain and osteoarthritis of the knee were
      identified from a GP database. Eligible patients were randomised to either
      'acupuncture plus usual care' and 'usual care' alone, with allocation
      appropriately concealed. Acupuncture consisted of up to 10 sessions usually
      weekly. Outcome measures included Western Ontario and McMaster Universities
      (WOMAC) index with the sample size for a full scale trial determined from the
      variance. RESULTS: From the GP database of 15,927 patients, 335 potential trial
      participants were identified and invited to participate. After screening
      responses, 78 (23%) were identified as eligible and 30 patients who responded
      most promptly were randomised to 'acupuncture plus usual care' (15 patients) and
      'usual care' alone (15 patients). Attendance for acupuncture appointments was
      high at 90% of the maximum. Although the trial was not powered to detect
      significant changes in outcome, the WOMAC pain index showed a statistically
      significant reduction at 3 months in the acupuncture group compared to usual
      care. This was not sustained at 12 months. The sample size for a fully powered
      two-arm trial was estimated to be 350. CONCLUSION: This pilot study provided the
      evidence that a fully powered study to explore the longer term impact of
      acupuncture would be worthwhile, and relevant design features for such a trial
      were determined. TRIAL REGISTRATION NUMBER: ISRCTN25134802.

PMID- 19852842
TI  - Quality control in microarray assessment of gene expression in human airway
      epithelium.
AB  - BACKGROUND: Microarray technology provides a powerful tool for defining gene
      expression profiles of airway epithelium that lend insight into the pathogenesis
      of human airway disorders. The focus of this study was to establish rigorous
      quality control parameters to ensure that microarray assessment of the airway
      epithelium is not confounded by experimental artifact. Samples (total n = 223) of
      trachea, large and small airway epithelium were collected by fiberoptic
      bronchoscopy of 144 individuals and hybridized to Affymetrix microarrays. The pre
      and post-chip quality control (QC) criteria established, included: (1) RNA
      quality, assessed by RNA Integrity Number (RIN) > or = 7.0; (2) cRNA transcript
      integrity, assessed by signal intensity ratio of GAPDH 3' to 5' probe sets < or =
      3.0; and (3) the multi-chip normalization scaling factor < or = 10.0. RESULTS: Of
      the 223 samples, all three criteria were assessed in 191; of these 184 (96.3%)
      passed all three criteria. For the remaining 32 samples, the RIN was not
      available, and only the other two criteria were used; of these 29 (90.6%) passed
      these two criteria. Correlation coefficients for pairwise comparisons of
      expression levels for 100 maintenance genes in which at least one array failed
      the QC criteria (average Pearson r = 0.90 +/- 0.04) were significantly lower (p <
      0.0001) than correlation coefficients for pairwise comparisons between arrays
      that passed the QC criteria (average Pearson r = 0.97 +/- 0.01). Inter-array
      variability was significantly decreased (p < 0.0001) among samples passing the QC
      criteria compared with samples failing the QC criteria. CONCLUSION: Based on the
      aberrant maintenance gene data generated from samples failing the established QC
      criteria, we propose that the QC criteria outlined in this study can accurately
      distinguish high quality from low quality data, and can be used to delete poor
      quality microarray samples before proceeding to higher-order biological analyses
      and interpretation.

PMID- 19852843
TI  - Irritable mood and the Diagnostic and Statistical Manual of Mental Disorders.
AB  - BACKGROUND: The terms 'irritable mood' and 'irritability' have been applied to
      describe and define a variety of different categories in the Diagnostic and
      Statistical Manual of Mental Disorders (DSM). More precise diagnostic terms and
      concepts are needed. METHODS: A concise critical historical review of DSM
      categories characterized by irritability, anger, and aggression is presented
      followed by recommendations. RESULTS: This analysis describes the broad ranging
      and imprecise use of the term irritability since the first DSM in 1952. A more
      age-appropriate and functional realignment of psychiatric categories linked to
      dysfunctional anger is suggested. Among other recommendations, this realignment
      would remove irritability as a problematic definer in the present DSM mood
      categories: expand oppositional defiant disorder to include adults; link the
      callous unemotional subtype of conduct disorder in adolescents to antisocial
      personality disorder; move intermittent explosive disorder to an appropriate
      category: and expand the term 'mood' to apply also to dysfunctional anger and
      anxiety. CONCLUSION: The non-specific term 'irritability' commonly used in the
      DSM has had an adverse effect on diagnostic specificity and thereby on treatment.
      Dysfunctional anger is a major mood disorder which merits a more prominent and
      better defined representation in psychiatric nomenclature.

PMID- 19852844
TI  - Mechanisms of FUS1/TUSC2 deficiency in mesothelioma and its tumorigenic
      transcriptional effects.
AB  - BACKGROUND: FUS1/TUSC2 is a novel tumor suppressor located in the critical 3p21.3
      chromosomal region frequently deleted in multiple cancers. We previously showed
      that Tusc2-deficient mice display a complex immuno-inflammatory phenotype with a
      predisposition to cancer. The goal of this study was to analyze possible
      involvement of TUSC2 in malignant pleural mesothelioma (MPM) - an aggressive
      inflammatory cancer associated with exposure to asbestos. METHODS: TUSC2
      insufficiency in clinical specimens of MPM was assessed via RT-PCR (mRNA level),
      Representational Oligonucleotide Microarray Analysis (DNA level), and
      immunohistochemical evaluation (protein level). A possible link between TUSC2
      expression and exposure to asbestos was studied using asbestos-treated
      mesothelial cells and ROS (reactive oxygen species) scavengers. Transcripional
      effects of TUSC2 in MPM were assessed through expression array analysis of TUSC2
      transfected MPM cells. RESULTS: Expression of TUSC2 was downregulated in
      approximately 84% of MM specimens while loss of TUSC2-containing 3p21.3 region
      observed in approximately 36% of MPMs including stage 1 tumors. Exposure to
      asbestos led to a transcriptional suppression of TUSC2, which we found to be ROS
      dependent. Expression array studies showed that TUSC2 activates transcription of
      multiple genes with tumor suppressor properties and down-regulates pro
      tumorigenic genes, thus supporting its role as a tumor suppressor. In agreement
      with our knockout model, TUSC2 up-regulated IL-15 and also modulated more than 40
      other genes (approximately 20% of total TUSC2-affected genes) associated with
      immune system. Among these genes, we identified CD24 and CD274, key
      immunoreceptors that regulate immunogenic T and B cells and play important roles
      in systemic autoimmune diseases. Finally, clinical significance of TUSC2
      transcriptional effects was validated on the expression array data produced
      previously on clinical specimens of MPM. In this analysis, 42 TUSC2 targets
      proved to be concordantly modulated in MM serving as disease discriminators.
      CONCLUSION: Our data support immuno-therapeutic potential of TUSC2, define its
      targets, and underscore its importance as a transcriptional stimulator of anti
      tumorigenic pathways.

PMID- 19852845
TI  - Survey of abuses against injecting drug users in Indonesia.
AB  - In Indonesia, an ongoing government "war on drugs" has resulted in numerous
      arrests and anecdotal reports of abuse in detention, but to date there has been
      little documentation or analysis of this issue. JANGKAR (also known in English as
      the Indonesian Harm Reduction Network), a nongovernmental organization (NGO)
      based in Jakarta, surveyed 1106 injecting drug users in 13 cities about their
      experiences of police abuse. Of those interviewed, 667 or 60% reported physical
      abuse by police. These findings indicate the importance of continuing efforts to
      promote police reform and harm reduction in Indonesia.

PMID- 19852846
TI  - The transplant iron score as a predictor of stem cell transplant survival.
AB  - Recent studies have suggested that the presence of iron overload prior to stem
      cell transplantation is associated with decreased survival. Within these studies,
      the criteria used to define iron overload have varied considerably. Given the
      lack of consensus regarding the definition of iron overload in the transplant
      setting, we sought to methodically examine iron status among transplant patients.
      We studied 78 consecutive patients at risk for transfusion-related iron overload
      (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either
      autologous or allogeneic stem cell transplant. Multiple measures of iron status
      were collected prior to transplantation and examined for their association with
      survival. Using this data, three potentially prognostic iron measures were
      identified and incorporated into a rational and unified scoring system. The
      resulting Transplant Iron Score assigns a point for each of the following
      variables: (1) greater than 25 red cell units transfused prior to
      transplantation; (2) serum ferritin > 1000 ng/ml; and (3) a semi-quantitative
      bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more
      closely associated with survival than any available single iron parameter. In
      multivariate analysis, we observed an independent effect of iron overload on
      transplant survival (p = 0.01) primarily attributable to an increase in early
      treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis,
      the predictive power of the iron score was most pronounced among allogeneic
      transplant patients, where a high score (> or = 2) was associated with a 50%
      absolute decrease in survival at one year. In summary, our results lend further
      credence to the notion that iron overload prior to transplant is detrimental and
      suggest iron overload may predispose to a higher rate of lethal infections.

PMID- 19852847
TI  - Novel cerebrovascular pathology in mice fed a high cholesterol diet.
AB  - BACKGROUND: Hypercholesterolemia causes atherosclerosis in medium to large sized
      arteries. Cholesterol is less known for affecting the microvasculature and has
      not been previously reported to induce microvascular pathology in the central
      nervous system (CNS). RESULTS: Mice with a null mutation in the low-density
      lipoprotein receptor (LDLR) gene as well as C57BL/6J mice fed a high cholesterol
      diet developed a distinct microvascular pathology in the CNS that differs from
      cholesterol-induced atherosclerotic disease. Microvessel diameter was increased
      but microvascular density and length were not consistently affected. Degenerative
      changes and thickened vascular basement membranes were present ultrastructurally.
      The observed pathology shares features with the microvascular pathology of
      Alzheimer's disease (AD), including the presence of string-like vessels. Brain
      apolipoprotein E levels which have been previously found to be elevated in LDLR-/
      mice were also increased in C57BL/6J mice fed a high cholesterol diet.
      CONCLUSION: In addition to its effects as an inducer of atherosclerosis in medium
      to large sized arteries, hypercholesterolemia also induces a microvascular
      pathology in the CNS that shares features of the vascular pathology found in AD.
      These observations suggest that high cholesterol may induce microvascular disease
      in a range of CNS disorders including AD.

PMID- 19852848
TI  - Third molar surgery: the patient's and the clinician's perspective.
AB  - BACKGROUND: In this report, the problems of third molar surgery have been
      reviewed from the perspective of both patient and clinician; additionally an
      overall analysis of preoperative imaging investigations was carried
      out.Specifically, three main areas of interest were investigated: the prediction
      of surgical difficulty and potential complications; the assessment of stress and
      anxiety and finally the assessment of postoperative complications and the
      surgeon's experience. FINDINGS: In the first study, the prediction of surgical
      difficulty and potential injury to the inferior alveolar nerve was assessed. This
      was achieved by examining the patient's orthopantomograms and by using the
      Pederson Difficulty Index (PDI). Several radiological signs were identified and a
      classification tree was created to help predict the incidence of such event.In
      the second study, a prospective assessment addressing the patient's stress and
      anxiety pre-, intra- and postoperatively was employed. Midazolam was the active
      drug used against placebo. Objective and subjective parameters were assessed,
      including measuring the cortisol level in saliva. Midazolam was found to
      significantly reduce anxiety levels and salivary cortisol was identified as an
      accurate anxiety marker.In the third study, postoperative complications and the
      surgeon's experience were examined. Few patients in this study suffered permanent
      nerve dysfunction. Junior surgeons reported a higher complication rate
      particularly in trismus, alveolar osteitis, infection and paraesthesia over the
      distributions of the inferior alveolar and lingual nerves. In apparent contrast,
      senior surgeons reported higher incidence of postoperative bleeding. DISCUSSION:
      These studies if well employed can lead to favourable alteration in patient
      management and might have a positive impact on future healthcare service.

PMID- 19852849
TI  - Empiric antibiotic therapy in acute uncomplicated urinary tract infections and
      fluoroquinolone resistance: a prospective observational study.
AB  - BACKGROUND: The aims of this study were to determine the antimicrobial
      susceptibility patterns of urinary isolates from community acquired acute
      uncomplicated urinary tract infections (uUTI) and to evaluate which antibiotics
      were empirically prescribed in the outpatient management of uUTI. METHODS: Among
      the patients which were admitted to outpatient clinics of Ankara University
      Medical Faculty, Ibni-Sina Hospital during 2005-2006, a total of 429 women
      between the age of 18 and 65 years old who were clinically diagnosed with uUTI
      and to whom prescribed empirical antibiotics were enrolled in this prospective
      observational study. Patients' demographical data, urine culture results,
      resistance rates to antimicrobial agents and prescribed empiric antimicrobial
      therapy were analyzed. RESULTS: Totally 390 (90.9%) patients among all study
      population were requested for urine culture by their physicians. 150 (38.5%) of
      these urine cultures were positive. The most common isolated uropathogen was
      Escherichia coli (E. coli) (71.3%). The variations of uropathogens according to
      age and menopause status were not significantly different.The resistance rates of
      E. coli isolates for ampicillin, ampicillin-sulbactam, amoxicillin-clavulonate,
      cefuroxime, ceftriaxone, fluoroquinolones (FQ), co-trimoxazole (TMP-SMX) and
      gentamicin were 55.1%, 32.7%, 32.7%, 23.4%, 15.9%, 25.2%, 41.1%, 6.1%
      respectively. FQ were the most common prescribed antibiotics (77.9%) (P < 0.001),
      followed by TMP-SMX (10.7%), fosfomycin (9.2%), nitrofurantoin (2.1%). Treatment
      durations were statistically longer than the recommended 3-day course (P <
      0.001). CONCLUSION: Empirical use of FQ in uUTI should be discouraged because of
      increased antimicrobial resistance rates.

PMID- 19852850
TI  - A simple cost-effective high performance liquid chromatographic assay of
      sulphadoxine in whole blood spotted on filter paper for field studies.
AB  - BACKGROUND: Artesunate plus sulphadoxine-pyrimethamine is one of the four
      artemisinin-based combination therapies currently recommended by WHO as first
      line treatment for falciparum malaria. Sulphadoxine-pyrimethamine is also used
      for intermittent preventive treatment for malaria in pregnancy. Drug use patterns
      and drug pharmacokinetics are important factors impacting the spread of drug
      resistant parasites hence it is imperative to monitor the effect of
      pharmacokinetic variability on therapeutic efficacy. Unfortunately, information
      on the pharmacokinetics of sulphadoxine in children and pregnant women with
      malaria is very limited. Methods for the assay of sulphadoxine-pyrimethamine have
      been previously reported, but they are not cost-effective and practicable in
      analytical laboratories in low resource areas where malaria is endemic. Efforts
      in this study were thus devoted to development and evaluation of a simple, cost
      effective and sensitive method for quantification of sulphadoxine in small
      capillary samples of whole blood dried on filter paper. METHODS: Sulphadoxine was
      determined in whole blood by reversed-phase high performance liquid
      chromatography with UV detection at 340 nm. Sulisoxazole (SLX) was used as
      internal standard. Chromatographic separation was achieved using a Beckman
      Coulter ODS C18 and a mobile phase consisting of 0.05 M phosphate buffer-methanol
      acetonitrile (70:17:13 V/V/V) containing 1% triethylamine solution. RESULTS:
      Standard curves from sulphadoxine-spiked blood added to filter paper were linear
      over the concentration range studied. Linear regression analysis yielded
      correlation coefficient r2>0.99 (n=6). Extraction recoveries were about 82-85%.
      The limit of quantification was 120 ng/ml while the within and between assay
      coefficient of variations were <10%. The inter-day precision was <5.8% and inter
      day accuracy ranged from 4.1 to 5.3%. There was no interference from endogenous
      compounds or any of the commonly used anti-malarial, analgesic and anti-infective
      drugs with the peaks of SDX or the internal standard. CONCLUSION: The recovery
      and accuracy of determination of SDX from whole blood filter paper samples using
      the method described in this study is satisfactory, thus making the method a
      valuable tool in epidemiological studies and therapeutic drug monitoring in
      developing endemic countries. Furthermore, the applicability of the method in
      studying the pharmacokinetic disposition of SDX in a patient suggests that the
      method is suitable in malaria endemic areas.

PMID- 19852852
TI  - Unilateral versus bilateral thyroarytenoid Botulinum toxin injections in adductor
      spasmodic dysphonia: a prospective study.
AB  - OBJECTIVES: In this preliminary prospective study, we compared unilateral and
      bilateral thyroarytenoid muscle injections of Botulinum toxin (Dysport) in 31
      patients with adductor spasmodic dysphonia, who had undergone more than 5
      consecutive Dysport injections (either unilateral or bilateral) and had completed
      5 concomitant self-rated efficacy and complication scores questionnaires related
      to the previous injections. We also developed a Neurophysiological Scoring (NPS)
      system which has utility in the treatment administration. METHOD AND MATERIALS:
      Data were gathered prospectively on voice improvement (self-rated 6 point scale),
      length of response and duration of complications (breathiness, cough, dysphagia
      and total voice loss). Injections were performed under electromyography (EMG)
      guidance. NPS scale was used to describe the EMG response. Dose and
      unilateral/bilateral injections were determined by clinical judgment based on
      previous response. Time intervals between injections were patient driven.
      RESULTS: Low dose unilateral Dysport injection was associated with no significant
      difference in the patient's outcome in terms of duration of action, voice score
      (VS) and complication rate when compared to bilateral injections. Unilateral
      injections were not associated with any post treatment total voice loss unlike
      the bilateral injections. CONCLUSION: Unilateral low dose Dysport injections are
      recommended in the treatment of adductor spasmodic dysphonia.

PMID- 19852851
TI  - Asthma and genes encoding components of the vitamin D pathway.
AB  - BACKGROUND: Genetic variants at the vitamin D receptor (VDR) locus are associated
      with asthma and atopy. We hypothesized that polymorphisms in other genes of the
      vitamin D pathway are associated with asthma or atopy. METHODS: Eleven candidate
      genes were chosen for this study, five of which code for proteins in the vitamin
      D metabolism pathway (CYP27A1, CYP27B1, CYP2R1, CYP24A1, GC) and six that are
      known to be transcriptionally regulated by vitamin D (IL10, IL1RL1, CD28, CD86,
      IL8, SKIIP). For each gene, we selected a maximally informative set of common
      SNPs (tagSNPs) using the European-derived (CEU) HapMap dataset. A total of 87
      SNPs were genotyped in a French-Canadian family sample ascertained through
      asthmatic probands (388 nuclear families, 1064 individuals) and evaluated using
      the Family Based Association Test (FBAT) program. We then sought to replicate the
      positive findings in four independent samples: two from Western Canada, one from
      Australia and one from the USA (CAMP). RESULTS: A number of SNPs in the IL10,
      CYP24A1, CYP2R1, IL1RL1 and CD86 genes were modestly associated with asthma and
      atopy (p < 0.05). Two-gene models testing for both main effects and the
      interaction were then performed using conditional logistic regression. Two-gene
      models implicating functional variants in the IL10 and VDR genes as well as in
      the IL10 and IL1RL1 genes were associated with asthma (p < 0.0002). In the
      replicate samples, SNPs in the IL10 and CYP24A1 genes were again modestly
      associated with asthma and atopy (p < 0.05). However, the SNPs or the orientation
      of the risk alleles were different between populations. A two-gene model
      involving IL10 and VDR was replicated in CAMP, but not in the other populations.
      CONCLUSION: A number of genes involved in the vitamin D pathway demonstrate
      modest levels of association with asthma and atopy. Multilocus models testing
      genes in the same pathway are potentially more effective to evaluate the risk of
      asthma, but the effects are not uniform across populations.

PMID- 19852854
TI  - Validation of AIDS-related mortality in Botswana.
AB  - BACKGROUND: Mortality data are used to conduct disease surveillance, describe
      health status and inform planning processes for health service provision and
      resource allocation. In many countries, HIV- and AIDS-related deaths are believed
      to be under-reported in government statistics. METHODS: To estimate the extent of
      under-reporting of HIV- and AIDS-related deaths in Botswana, we conducted a
      retrospective study of a sample of deaths reported in the government vital
      registration database from eight hospitals, where more than 40% of deaths in the
      country in 2005 occurred. We used the consensus of three physicians conducting
      independent reviews of medical records as the gold standard comparison. We
      examined the sensitivity, specificity and other validity statistics. RESULTS: Of
      the 5276 deaths registered in the eight hospitals, 29% were HIV- and AIDS
      related. The percentage of HIV- and AIDS-related deaths confirmed by physician
      consensus (positive predictive value) was 95.4%; however, the percentage of non
      HIV- and non-AIDS-related deaths confirmed (negative predictive value) was only
      69.1%. The sensitivity and specificity of the vital registration system was 55.7%
      and 97.3%, respectively. After correcting for misclassification, the percentage
      of HIV- and AIDS--related deaths was estimated to be in the range of 48.8% to
      54.4%, depending on the definition. CONCLUSION: Improvements in hospitals and
      within government offices are necessary to strengthen the vital registration
      system. These should include such strategies as training physicians and coders in
      accurate reporting and recording of death statistics, implementing continuous
      quality assurance methods, and working with the government to underscore the
      importance of using mortality statistics in future evidence-based planning.

PMID- 19852853
TI  - Efficacy of customised foot orthoses in the treatment of Achilles tendinopathy:
      study protocol for a randomised trial.
AB  - BACKGROUND: Achilles tendinopathy is a common condition that can cause marked
      pain and disability. Numerous non-surgical treatments have been proposed for the
      treatment of this condition, but many of these treatments have a poor or non
      existent evidence base. The exception to this is eccentric calf muscle exercises,
      which have become a standard non-surgical intervention for Achilles tendinopathy.
      Foot orthoses have also been advocated as a treatment for Achilles tendinopathy,
      but the long-term efficacy of foot orthoses for this condition is unknown. This
      manuscript describes the design of a randomised trial to evaluate the efficacy of
      customised foot orthoses to reduce pain and improve function in people with
      Achilles tendinopathy. METHODS: One hundred and forty community-dwelling men and
      women aged 18 to 55 years with Achilles tendinopathy (who satisfy inclusion and
      exclusion criteria) will be recruited. Participants will be randomised, using a
      computer-generated random number sequence, to either a control group (sham foot
      orthoses made from compressible ethylene vinyl acetate foam) or an experimental
      group (customised foot orthoses made from semi-rigid polypropylene). Both groups
      will be prescribed a calf muscle eccentric exercise program, however, the primary
      difference between the groups will be that the experimental group receive
      customised foot orthoses, while the control group receive sham foot orthoses. The
      participants will be instructed to perform eccentric exercises 2 times per day, 7
      days per week, for 12 weeks. The primary outcome measure will be the total score
      of the Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaire.
      The secondary outcome measures will be participant perception of treatment
      effect, comfort of the foot orthoses, use of co-interventions, frequency and
      severity of adverse events, level of physical activity and health-related quality
      of life (assessed using the Short-Form-36 questionnaire - Version two). Data will
      be collected at baseline, then at 1, 3, 6 and 12 months. Data will be analysed
      using the intention to treat principle. DISCUSSION: This study is the first
      randomised trial to evaluate the long-term efficacy of customised foot orthoses
      for the treatment of Achilles tendinopathy. The study has been pragmatically
      designed to ensure that the study findings are generalisable to clinical
      practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      Number: ACTRN12609000829213.

PMID- 19852855
TI  - An insight into the role of phosphotransacetylase (pta) and the acetate/acetyl
      CoA node in Escherichia coli.
AB  - BACKGROUND: Acetate metabolism in Escherichia coli plays an important role in the
      control of the central metabolism and in bioprocess performance. The main
      problems related to the use of E. coli as cellular factory are i) the deficient
      utilization of carbon source due to the excretion of acetate during aerobic
      growth, ii) the inhibition of cellular growth and protein production by acetate
      and iii) the need for cofactor recycling (namely redox coenzymes and free CoASH)
      to sustain balanced growth and cellular homeostasis. RESULTS: This work analyzes
      the effect of mutations in the acetate excretion/assimilation pathways, acetyl
      CoA synthethase (acs) and phosphotransacetylase (pta), in E. coli BW25113 grown
      on glucose or acetate minimal media. Biomass and metabolite production, redox
      (NADH/NAD+) and energy (ATP) state, enzyme activities and gene expression
      profiles related to the central metabolism were analyzed. The knock-out of pta
      led to a more altered phenotype than that of acs. Deletion of pta reduced the
      ability to grow on acetate as carbon source and strongly affected the expression
      of several genes related to central metabolic pathways. CONCLUSION: Results
      showed that pta limits biomass yield in aerobic glucose cultures, due to acetate
      production (overflow metabolism) and its inefficient use during glucose
      starvation. Deletion of pta severely impaired growth on acetate minimal medium
      and under anaerobiosis due to decreased acetyl-coenzyme A synthethase, glyoxylate
      shunt and gluconeogenic activities, leading to lower growth rate. When acetate is
      used as carbon source, the joint expression of pta and acs is crucial for growth
      and substrate assimilation, while pta deletion severely impaired anaerobic
      growth. Finally, at an adaptive level, pta deficiency makes the strain more
      sensitive to environmental changes and de-regulates the central metabolism.

PMID- 19852856
TI  - A fast radiotherapy paradigm for anal cancer with volumetric modulated arc
      therapy (VMAT).
AB  - BACKGROUND/PURPOSE: Radiotherapy (RT) volumes for anal cancer are large and of
      moderate complexity when organs at risk (OAR) such as testis, small bowel and
      bladder are at least partially to be shielded. Volumetric intensity modulated arc
      therapy (VMAT) might provide OAR-shielding comparable to step-and-shoot intensity
      modulated radiotherapy (IMRT) for this tumor entity with better treatment
      efficiency. MATERIALS AND METHODS: Based on treatment planning CTs of 8 patients,
      we compared dose distributions, comformality index (CI), homogeneity index (HI),
      number of monitor units (MU) and treatment time (TTT) for plans generated for
      VMAT, 3D-CRT and step-and-shoot-IMRT (optimized based on Pencil Beam (PB) or
      Monte Carlo (MC) dose calculation) for typical anal cancer planning target
      volumes (PTV) including inguinal lymph nodes as usually treated during the first
      phase (0-36 Gy) of a shrinking field regimen. RESULTS: With values of 1.33 +/-
      0.21/1.26 +/- 0.05/1.3 +/- 0.02 and 1.39 +/- 0.09, the CI's for IMRT (PB
      Corvus/PB-Hyperion/MC-Hyperion) and VMAT are better than for 3D-CRT with 2.00 +/-
      0.16. The HI's for the prescribed dose (HI36) for 3D-CRT were 1.06 +/- 0.01 and
      1.11 +/- 0.02 for VMAT, respectively and 1.15 +/- 0.02/1.10 +/- 0.02/1.11 +/-
      0.08 for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion). Mean TTT and MU's for 3D-CRT
      is 220s/225 +/- 11MU and for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion) is
      575s/1260 +/- 172MU, 570s/477 +/- 84MU and 610s748 +/- 193MU while TTT and MU for
      two-arc-VMAT is 290s/268 +/- 19MU. CONCLUSION: VMAT provides treatment plans with
      high conformity and homogeneity equivalent to step-and-shoot-IMRT for this mono
      concave treatment volume. Short treatment delivery time and low primary MU are
      the most important advantages.

PMID- 19852857
TI  - Barriers to the effective treatment and prevention of malaria in Africa: A
      systematic review of qualitative studies.
AB  - BACKGROUND: In Africa, an estimated 300-500 million cases of malaria occur each
      year resulting in approximately 1 million deaths. More than 90% of these are in
      children under 5 years of age. To identify commonly held beliefs about malaria
      that might present barriers to its successful treatment and prevention, we
      conducted a systematic review of qualitative studies examining beliefs and
      practices concerning malaria in sub-Saharan African countries. METHODS: We
      searched Medline and Scopus (1966-2009) and identified 39 studies that employed
      qualitative methods (focus groups and interviews) to examine the knowledge,
      attitudes, and practices of people living in African countries where malaria is
      endemic. Data were extracted relating to study characteristics, and themes
      pertaining to barriers to malaria treatment and prevention. RESULTS: The majority
      of studies were conducted in rural areas, and focused mostly or entirely on
      children. Major barriers to prevention reported included a lack of understanding
      of the cause and transmission of malaria (29/39), the belief that malaria cannot
      be prevented (7/39), and the use of ineffective prevention measures (12/39).
      Thirty-seven of 39 articles identified barriers to malaria treatment, including
      concerns about the safety and efficacy of conventional medicines (15/39),
      logistical obstacles, and reliance on traditional remedies. Specific barriers to
      the treatment of childhood malaria identified included the belief that a child
      with convulsions could die if given an injection or taken to hospital (10/39).
      CONCLUSION: These findings suggest that large-scale malaria prevention and
      treatment programs must account for the social and cultural contexts in which
      they are deployed. Further quantitative research should be undertaken to more
      precisely measure the impact of the themes uncovered by this exploratory
      analysis.

PMID- 19852858
TI  - Bcl-2 expression is altered with ovarian tumor progression: an
      immunohistochemical evaluation.
AB  - BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy. The ovarian
      tumor microenvironment is comprised of tumor cells, surrounding stroma, and
      circulating lymphocytes, an important component of the immune response, in
      tumors. Previous reports have shown that the anti-apoptotic protein Bcl-2 is
      overexpressed in many solid neoplasms, including ovarian cancers, and contributes
      to neoplastic transformation and drug-resistant disease, resulting in poor
      clinical outcome. Likewise, studies indicate improved clinical outcome with
      increased presence of lymphocytes. Therefore, we sought to examine Bcl-2
      expression in normal, benign, and cancerous ovarian tissues to determine the
      potential relationship between epithelial and stromal Bcl-2 expression in
      conjunction with the presence of lymphocytes for epithelial ovarian tumor
      progression. METHODS: Ovarian tissue sections were classified as normal (n = 2),
      benign (n = 17) or cancerous (n = 28) and immunohistochemically stained for Bcl
      2. Bcl-2 expression was assessed according to cellular localization, extent, and
      intensity of staining. The number of lymphocyte nests as well as the number of
      lymphocytes within these nests was counted. RESULTS: While Bcl-2 staining
      remained cytoplasmic, both percent and intensity of epithelial and stromal Bcl-2
      staining decreased with tumor progression. Further, the number of lymphocyte
      nests dramatically increased with tumor progression. CONCLUSION: The data suggest
      alterations in Bcl-2 expression and lymphocyte infiltration correlate with
      epithelial ovarian cancer progression. Consequently, Bcl-2 expression and
      lymphocyte status may be important for prognostic outcome or useful targets for
      therapeutic intervention.

PMID- 19852859
TI  - Five-year follow up of genotypic resistance patterns in HIV-1 subtype C infected
      patients in Botswana after failure of thymidine analogue-based regimens.
AB  - OBJECTIVE: Our objective was to establish genotypic resistance profiles among the
      4% of Batswana patients who experienced virologic failure while being followed
      within Botswana's National Antiretroviral Treatment Program between 2002 and
      2007. METHODS: At the beginning of the national program in 2002, almost all
      patients received stavudine (d4T), together with didanosine (ddI), as part of
      their first nucleoside reverse transcriptase inhibitor (NRTI)-based regimen
      (Group 1). In contrast, the standard of care for all patients subsequently
      enrolled (2002-2007) included zidovudine/lamivudine (ZDV/3TC) (Group 2).
      Genotypes were analyzed in 26 patients from Group 1 and 37 patients from Group 2.
      Associations between mutations were determined using Pearson's correlation
      coefficient and Jaccard's coefficient of similarity. RESULTS: Seventy-eight
      percent of genotyped patients possessed mutations associated with protease
      inhibitor (PI) resistance while 87% and 90%, respectively, exhibited mutations
      associated with NRTIs and non-nucleoside reverse transcriptase inhibitors
      (NNRTIs). The most frequent PI mutations involving resistance to NFV were L90M
      (25.2%) and D30N (16.2%), but mutations at positions K45Q and D30N were often
      observed in tandem (P = 60.5, J = 50; p = 0.002; Group 2) alongside Q61E in 42.8%
      of patients who received ZDV/3TC. Both major patterns of thymidine analogue
      mutations, TAM 1 (48%) and TAM 2 (59%), were represented in patients from Group 1
      and 2, although M184V was higher among individuals who had initially received ddI
      (61% versus 40.5%). In contrast, L74V was more frequent among individuals from
      Group 2 (16.2% versus 7.7%). Differences in regard to NNRTI mutations were also
      observed between Group 1 and Group 2 patients. CONCLUSION: Despite a low rate of
      therapeutic failure (4%) among these patients, those who failed possessed high
      numbers of resistance mutations as well as novel resistance mutations and/or
      polymorphisms at sites within reverse transcriptase and protease.

PMID- 19852861
TI  - GAP-43 expression correlates with spinal motoneuron regeneration following root
      avulsion.
AB  - BACKGROUND: The growth-associated protein GAP-43 plays a crucial role in axonal
      regeneration in injured neurons. METHODS: We have used immunohistochemistry to
      investigate the expression of GAP-43 in spinal motoneurons during nerve
      reconstruction following root avulsion in the neonatal and adult rats. RESULTS:
      Following the injury, GAP-43-immunoreactivity (IR) could be found in adult
      avulsed motoneurons as early as 1 day, increased from 3 to 7 days and reached a
      maximal level at 2 weeks post-injury. The up-regulation of GAP-43 in adult
      avulsed motoneurons was accompanied with the axonal regeneration indicated by
      numerous regenerating motor axons entering the reimplanted ventral root and
      nerve. In contrast, GAP-43-IR could not be found in the neonatal avulsed
      motoneurons at any examined post-injury time points. This failure of up
      regulation of GAP-43 was coincident with no axonal regeneration in the
      reimplanted nerve in the neonatal rats. CONCLUSION: Close association of GAP-43
      expression and capacity of regeneration in reimplanted spinal nerve of avulsed
      motoneurons suggests that GAP-43 is a potential therapeutic target for treatment
      of root avulsion of brachial plexus.

PMID- 19852860
TI  - Preliminary molecular characterization of the human pathogen Angiostrongylus
      cantonensis.
AB  - BACKGROUND: Human angiostrongyliasis is an emerging food-borne public health
      problem, with the number of cases increasing worldwide, especially in mainland
      China. Angiostrongylus cantonensis is the causative agent of this severe disease.
      However, little is known about the genetics and basic biology of A. cantonensis.
      RESULTS: A cDNA library of A. cantonensis fourth-stage larvae was constructed,
      and approximately 1,200 clones were sequenced. Bioinformatic analyses revealed
      378 cDNA clusters, 54.2% of which matched known genes at a cutoff expectation
      value of 10(-20). Of these 378 unique cDNAs, 168 contained open reading frames
      encoding proteins containing an average of 238 amino acids. Characterization of
      the functions of these encoded proteins by Gene Ontology analysis showed
      enrichment in proteins with binding and catalytic activity. The observed pattern
      of enzymes involved in protein metabolism, lipid metabolism and glycolysis may
      reflect the central nervous system habitat of this pathogen. Four proteins were
      tested for their immunogenicity using enzyme-linked immunosorbent assays and
      histopathological examinations. The specificity of each of the four proteins was
      superior to that of crude somatic and excretory/secretory antigens of larvae,
      although their sensitivity was relatively low. We further showed that mice
      immunized with recombinant cystatin, a product of one of the four cDNA candidate
      genes, were partially protected from A. cantonensis infection. CONCLUSION: The
      data presented here substantially expand the available genetic information about
      the human pathogen A. cantonensis, and should be a significant resource for
      angiostrongyliasis researchers. As such, this work serves as a starting point for
      molecular approaches for diagnosing and controlling human angiostrongyliasis.

PMID- 19852862
TI  - Functional recovery after implantation of artificial nerve grafts in the rat- a
      systematic review.
AB  - PURPOSE: The aim of this study was to compare functional data of different nerve
      gap bridging materials evaluated in rat experiments by means of a systematic
      review. MATERIALS AND METHODS: A systematic review was conducted, searching
      MEDLINE, HTS and CENTRAL to identify all trials evaluating functional recovery of
      artificial nerve conduits in the rat model. RESULTS: There was a trend towards a
      favourable outcome of conduits coated with Schwann-cells compared to the plain
      synthetics. Histomorphometry, electrophysiology and muscle-weight correlated
      poorly with functional outcome. CONCLUSION: Schwann-cell coated conduits showed
      promising results concerning functional recovery. Further standardization in
      outcome reporting is encouraged.

PMID- 19852864
TI  - Using milk flow rate to investigate milk ejection in the left and right breasts
      during simultaneous breast expression in women.
AB  - BACKGROUND: Milk ejection is essential for a successful lactation, however
      techniques to measure milk ejection in women are often complex and invasive.
      Recent research has demonstrated that at milk ejection, milk duct diameter
      increased in the breast (measured by ultrasound) at the same time as milk flow
      rate increased (measured using a weigh balance). This study aimed to evaluate a
      purpose-built continuous weigh balance (Showmilk, Medela AG) to measure changes
      in milk flow rate from the breast to identify milk ejections during milk
      expression. In addition, the Showmilk was used to determine if milk ejection
      occurred simultaneously in both breasts during double pumping. METHODS: Increased
      milk flow rates during single pumping were compared to simultaneous ultrasound
      measurements of increased milk duct diameters in 14 mothers. In addition,
      increases in milk flow rate were compared between the left and right breasts of
      28 mothers during double pumping for 15 minutes with two separate electric breast
      pumps attached to two Showmilks to record milk flow rate. RESULTS: Increased milk
      flow rates were associated with increased milk duct diameters during single
      pumping. The mean number of milk ejections was not different between the Showmilk
      (4.2 +/- 2.0) and ultrasound (4.5 +/- 1.5) techniques. Overall, 67 milk ejections
      were measured and of these, 48 (72%) were identified by both techniques. The left
      and right breasts responded synchronously with 95.5% of the flow rate increases
      corresponding between the breasts. The mean number of milk ejections identified
      by an increase in milk flow rate during double pumping was 5.1 +/- 1.7 and 5.0 +/
      1.7 for the left and right breasts, respectively. In addition, mothers chose the
      same expression vacuum for the left (-198 +/- 31 mmHg) and right (193 +/- 33
      mmHg) breasts. CONCLUSION: The Showmilk can simply and non-invasively record milk
      ejections by measuring increases in milk flow rate that correspond with increases
      in milk duct diameter. For the first time measurement of milk flow rate has been
      used to confirm that milk ejections occur simultaneously in the left and right
      breasts during double pumping. The use of the Showmilk will facilitate further
      research into the relationship of milk ejection and milk removal.

PMID- 19852863
TI  - Molecular characterization of the Great Lakes viral hemorrhagic septicemia virus
      (VHSV) isolate from USA.
AB  - BACKGROUND: Viral hemorrhagic septicemia virus (VHSV) is a highly contagious
      viral disease of fresh and saltwater fish worldwide. VHSV caused several large
      scale fish kills in the Great Lakes area and has been found in 28 different host
      species. The emergence of VHS in the Great Lakes began with the isolation of VHSV
      from a diseased muskellunge (Esox masquinongy) caught from Lake St. Clair in
      2003. VHSV is a member of the genus Novirhabdovirus, within the family
      Rhabdoviridae. It has a linear single-stranded, negative-sense RNA genome of
      approximately 11 kbp, with six genes. VHSV replicates in the cytoplasm and
      produces six monocistronic mRNAs. The gene order of VHSV is 3'-N-P-M-G-NV-L-5'.
      This study describes molecular characterization of the Great Lakes VHSV strain
      (MI03GL), and its phylogenetic relationships with selected European and North
      American isolates. RESULTS: The complete genomic sequences of VHSV-MI03GL strain
      was determined from cloned cDNA of six overlapping fragments, obtained by RT-PCR
      amplification of genomic RNA. The complete genome sequence of MI03GL comprises
      11,184 nucleotides (GenBank GQ385941) with the gene order of 3'-N-P-M-G-NV-L-5'.
      These genes are separated by conserved gene junctions, with di-nucleotide gene
      spacers. The first 4 nucleotides at the termini of the VHSV genome are
      complementary and identical to other novirhadoviruses genomic termini. Sequence
      homology and phylogenetic analysis show that the Great Lakes virus is closely
      related to the Japanese strains JF00Ehi1 (96%) and KRRV9822 (95%). Among other
      novirhabdoviruses, VHSV shares highest sequence homology (62%) with snakehead
      rhabdovirus. CONCLUSION: Phylogenetic tree obtained by comparing 48 glycoprotein
      gene sequences of different VHSV strains demonstrate that the Great Lakes VHSV is
      closely related to the North American and Japanese genotype IVa, but forms a
      distinct genotype IVb, which is clearly different from the three European
      genotypes. Molecular characterization of the Great Lakes isolate will be helpful
      in studying the pathogenesis of VHSV using a reverse genetics approach and
      developing efficient control strategies.

PMID- 19852865
TI  - Secular trend of very low birth weight rate in Porto Alegre, Southern Brazil.
AB  - The strong association of very low birth weight (VLBW; <1500 g) with infant
      mortality is well known. There are no data related to VLBW trends in Brazil
      although findings from some large surveys carried out in small- and medium-sized
      cities have demonstrated an increase in low birth weight (LBW; <2500 g) rates
      over the last 30 years. The aim of this study was to evaluate the secular trend
      of VLBW in the city of Porto Alegre, a large city in a developed area in southern
      Brazil, and the potential determinants of this trend during the 1990s and early
      2000s. This is a registry-based study. Data were obtained from birth certificates
      of all live births in the city from 1994 to 2005. The variables analysed were:
      VLBW as the dependent variable and maternal age and schooling, type of delivery,
      type of hospital, number of live births, gestational age, newborn gender and
      unemployment rate. The incidence ratio rate (IRR) using Poisson regression was
      calculated to identify possible trends in VLBW rates. Poisson regressions were
      performed in order to assess the influence of some independent variables on VLBW.
      A total of 257,740 singleton newborns were delivered in the city during the
      period, with a steady reduction in the total number of live births per year from
      23,296 in 1994 to 18,325 in 2005. The results showed a small but significant
      increase in VLBW (p for trend=0.049). There was a significant trend towards
      adequacy for gestational age per birth weight, suggesting a reduction in rates of
      intrauterine growth restriction (IUGR) (p<0.001). The findings showed a
      significant increase of 1% per year in the probability of VLBW. The main risk
      factors were related to VLBW mothers with low levels of schooling, public
      hospitals and multiparity and nulliparity. After adjustment, nulliparity remained
      as a significant risk factor. The interaction between type of hospital and type
      of delivery indicated that the probability for VLBW was 3.6 times higher
      (p<0.001) among those born in public hospitals by Caesarean section than those
      born in private hospitals by vaginal delivery. The results show that southern
      Brazil is going through a demographic transition characterized by a significant
      decrease in number of live births associated with a small increase in VLBW rates,
      a decrease in IUGR rates and stabilization of LBW.

PMID- 19852866
TI  - Using a reproductive life course approach to understand contraceptive method use
      in Australia.
AB  - This paper examines contraceptive method use at different stages of the
      reproductive life course. Previous research on contraceptive practice in
      developed countries typically applies age as a proxy for reproductive history.
      While age is an essential and useful life course measure for understanding
      contraceptive use, investigations of contraceptive practice should also consider
      parity and fertility intentions, as they may be more accurate measures of
      reproductive life course stage. Analysis is based on data collected in the 2005
      Household, Income and Labour Dynamics in Australia (HILDA) survey, a nationally
      representative sample of women of reproductive age (18-44). For women at risk of
      pregnancy, the most commonly used methods are easily reversed methods such as the
      oral contraceptive pill (30%) and condom (23%), medium-term methods such as the
      intrauterine device and implantation (5%) and permanent methods (7% tubal
      ligation and 9% vasectomy of partner). Logistic regression models are used to
      investigate the use of four popular contraceptive methods by parity, age and
      fertility intentions controlling for socio-demographic factors. The main findings
      indicate that the use of these methods varies substantially by the stage of a
      woman's reproductive life course: age, parity and fertility intentions are all
      associated with method use.

PMID- 19852867
TI  - Effect of inbreeding on weight gain of offspring from birth to 12 months after
      birth: a study from Iran.
AB  - Consanguinity, the marriage between relatives, has been associated with adverse
      child health outcomes. The objective of the present study was to assess the
      effect of consanguinity on offspring weight gain from birth to 12 months after
      birth. Data were collected on 250 consecutive live-born singleton newborns
      referred to a local health centre in Shiraz (Fars province, southern Iran).
      Collected data covered socio-demographic characteristics (such as parental age at
      delivery and parental education), sex, birth order, weights from birth to 12
      months after birth and consanguinity of marriages of parents. Considering the low
      prevalence of double first cousin, first cousin once removed, second cousin, and
      beyond second cousin marriages, only first cousin and unrelated marriages were
      included in the study. The study population consisted of a total of 207 newborns
      (57 offspring of first cousins, 150 offspring of unrelated marriages). Based on
      the results of repeated measurements analysis of variance, weight gain was
      associated with type of marriage (p=0.018), sex of offspring (p=0.001) and
      paternal education (p<0.001). There was no interaction between type of marriage
      and sex (p=0.831). Birth weight was not affected by type of marriage (p=0.46).
      There was significant interaction between inbreeding and time (p=0.034).
      Offspring of consanguineous marriages showed lower weight gain in comparison with
      those of unrelated marriages during 3-12 months after birth.

PMID- 19852868
TI  - Peri-operative use of dexmedetomidine in airway reconstruction surgery for
      obstructive sleep apnoea.
AB  - OBJECTIVE: To evaluate the peri-operative usefulness of dexmedetomidine in
      obstructive sleep apnoea surgery. METHODS: In a clinical audit, patients were
      divided into a study group (dexmedetomidine used; n = 125; 82.9 per cent males,
      17.1 per cent females; mean age 48.1 years) and a control group (dexmedetomidine
      not used; n = 143; 85.5 per cent males, 14.5 per cent females; mean age 47.4
      years). The selected outcome measures were mean arterial pressure, use of anti
      hypertensives and use of opioids. RESULTS: Mean arterial pressure was stable
      (i.e. below 100 mmHg) in 93.3 per cent of the study group and 72.0 per cent of
      the control group (relative risk 1.30, 95 per cent confidence interval 1.14
      1.47). The use of glyceryl trinitrate and hydralazine was significantly less in
      the study group, compared with controls (p = 0.005 and <0.001, respectively).
      Study group patients underwent more procedures than control patients (p < 0.001)
      and were more likely to require morphine. No difference was noted in the median
      dose of opioids. CONCLUSION: Dexmedetomidine improves haemodynamic stability in
      patients undergoing surgery for obstructive sleep apnoea. It is reliable and
      reduces the need for polypharmacy. Its opioid-sparing action has been established
      in the literature; however, this was not demonstrated in our study.

PMID- 19852869
TI  - Results for audiology and distortion product and transient evoked otoacoustic
      emissions in patients with systemic lupus erythematosus.
AB  - The aim of the current study was to investigate hearing loss and cochlear
      function in patients with systemic lupus erythematosus, using audiology,
      distortion product otoacoustic emissions and transient evoked otoacoustic
      emissions. STUDY DESIGN: Prospective, case-control study. METHODS: The study
      included 26 randomised patients with systemic lupus erythematosus (52 ears) and
      30 healthy control subjects (60 ears). Pure tone audiometry was performed at 250
      and 500 Hz and at 1, 2, 4, 6, 8, 10, 12, 14 and 16 kHz. Distortion product
      otoacoustic emissions and transient evoked otoacoustic emissions were measured
      using Biologic System equipment with Scout Acoustic Emissions System software.
      RESULTS: The distortion product otoacoustic emission signal responses were
      significantly different only at 750 Hz, while the distortion product otoacoustic
      emission signal-noise ratios were significantly different at 750 Hz and 6 kHz (p
      < 0.05), comparing patients and controls. The transient evoked otoacoustic
      emission signal-noise ratios were significantly different at 2 and 3 kHz,
      comparing patients and controls (p < 0.05). The transient evoked otoacoustic
      emission total signal-noise ratios were significantly different, comparing
      patients and controls (p < 0.05). In addition, the pure tone audiometry
      thresholds were significantly different at 250 and 500 Hz and at 1, 2, 10 and 12
      kHz, comparing patients and controls (p < 0.05). CONCLUSION: Our findings do not
      completely agree with those of previous temporal bone histopathological studies.
      However, our results do support a general picture of low frequency hearing loss
      in systemic lupus erythematosus patients. We consider these results to be related
      to endolymphatic and cochlear hydrops, and we suggest that electrocochleography
      could be performed in further studies for clarification of this subject.

PMID- 19852870
TI  - 'Honeycomb' tegmen: multiple tegmen defects associated with superior semicircular
      canal dehiscence.
AB  - OBJECTIVE: To report the coexistence of multiple tegmen defects, forming a
      'honeycomb' pattern, together with dehiscence of the superior semicircular canal.
      CASE REPORTS: We describe three cases in which the above findings were noted, and
      we review the relevant literature. CONCLUSION: Superior semicircular canal
      dehiscence is defined as the absence of portions of bone over the canal along the
      floor of the middle fossa. Most published articles describe the defect as an
      isolated finding which is either unilateral or bilateral. Studies on temporal
      bones show either a defect over the superior semicircular canal or isolated
      defects over the tegmen. We describe three cases in which we found multiple
      tegmen defects, giving a characteristic honeycomb appearance, coexisting with
      dehiscence over the superior semicircular canal. This finding, which supports the
      theory of a developmental defect as the origin of the condition, has not
      previously been reported. A literature review is presented, with discussion of
      the aetiology and management of superior semicircular canal dehiscence.

PMID- 19852871
TI  - Laryngeal sensory testing in the assessment of patients with laryngopharyngeal
      reflux.
AB  - Laryngopharyngeal reflux is commonly encountered in the ENT out-patient setting.
      It leads to impaired sensory capacity of the laryngeal mucosa. The sensory
      integrity of the laryngopharynx can be evaluated through endoscopic
      administration of pulsed air, which stimulates the laryngeal adductor reflex. The
      pressure of air needed to elicit this reflex indicates the degree of sensory
      impairment. Such laryngeal sensory testing gives a quantifiable means of
      assessment in patients with laryngopharyngeal reflux, and can be used to measure
      the response to treatment. Laryngeal sensory testing is safe and well tolerated
      by patients.

PMID- 19852872
TI  - Comparison of (6 S)-5-methyltetrahydrofolic acid v. folic acid as the reference
      folate in longer-term human dietary intervention studies assessing the relative
      bioavailability of natural food folates: comparative changes in folate status
      following a 16-week placebo-controlled study in healthy adults.
AB  - Folic acid (pteroylmonoglutamic acid) has historically been used as the reference
      folate in human intervention studies assessing the relative bioavailability of
      dietary folate. Recent studies using labelled folates indicated different plasma
      response kinetics to folic acid than to natural (food) folates, thus obviously
      precluding its use in single-dose experiments. Since differences in tissue
      distribution and site of biotransformation were hypothesised, the question is
      whether folic acid remains suitable as a reference folate for longer-term
      intervention studies, where the relative bioavailability of natural (food) folate
      is assessed based on changes in folate status. Healthy adults aged 18-65 years (n
      163) completed a 16-week placebo-controlled intervention study in which the
      relative bioavailability of increased folate intake (453 nmol/d) from folate-rich
      foods was assessed by comparing changes in plasma and erythrocyte folate
      concentration with changes induced by an equal reference dose of supplemental
      (6S)-5-methyltetrahydrofolic acid or folic acid. The relative increase in plasma
      folate concentration in the food group was 31 % when compared with that induced
      by folic acid, but 39 % when compared with (6S)-5-methyltetrahydrofolic acid. The
      relative increase in erythrocyte folate concentration in the food group when
      compared with that induced by folic acid was 43 %, and 40 % when compared with
      (6S)-5-methyltetrahydrofolic acid. When recent published observations were
      additionally taken into account it was concluded that, in principle, folic acid
      should not be used as the reference folate when attempting to estimate relative
      natural (food) folate bioavailability in longer-term human intervention studies.
      Using (6S)-5-methyltetrahydrofolic acid as the reference folate would avoid
      future results' validity being questioned.

PMID- 19852873
TI  - Calcium requirements for bone growth in Canadian boys and girls during
      adolescence.
AB  - Adequate dietary intake during the growth period is critical for bone mineral
      accretion. In 1997, an adequate intake (AI) of 1300 mg/d Ca was set for North
      American adolescents aged 9-18 years based on best available data. We determined
      bone Ca accrual values from age 9 to 18 years taking into account sex and
      maturity. Furthermore, we used the accrual data to estimate adolescents' Ca
      requirements. Total body bone mineral content (TBBMC) of eighty-five boys and
      sixty-seven girls participating in the Saskatchewan Paediatric Bone Mineral
      Accrual Study were used to determine annual TBBMC accumulation over the pubertal
      growth period. Using a similar factorial approach as the AI, we estimated Ca
      requirements of adolescent boys and girls for two age groups: 9-13 and 14-18
      years. Between 9 and 18 years, boys accrued 198.8 (SD 74.5) g bone mineral
      content (BMC) per year, equivalent to 175.4 (SD 65.7) mg Ca per d with the
      maximum BMC accrual of 335.9 g from age 13 to 14 years. Girls had 138.1 (SD 64.2)
      g BMC per year, equalling121.8 (SD 56.6) mg Ca per d with the maximum annual BMC
      accrual of 266.0 g from age 12 to 13 years. Differences were observed between
      both sex and age groups with respect to Ca needs: boys and girls aged 9-13 years
      would require 1000-1100 mg/d Ca, and from age 14 to 18 years, the mean Ca
      requirements would be relatively stable at 1000 mg/d for girls but would rise to
      1200 mg/d for boys.

PMID- 19852874
TI  - Building skeletons during adolescence: what is the target?

PMID- 19852875
TI  - EELS of niobium and stoichiometric niobium-oxide phases--Part II: quantification.
AB  - A comprehensive electron energy-loss spectroscopy (EELS) study of niobium (Nb)
      and stable Nb-oxide phases (NbO, NbO2, Nb2O5) was carried out. Part II of this
      work is devoted to quantitative EELS by means of experimental k-factors derived
      from the intensity ratio of the O-K edge and the Nb-M4,5 or Nb-M2,3 edges for all
      three stable Nb-oxides. The precision and accuracy of the quantification are
      investigated with respect to the influence of intensity-measurement energy
      windows, background subtraction, and sample thickness. Integration-window widths
      allowing optimum accuracy are determined. Owing to background-subtraction errors,
      the Nb-M4,5 edges rather than Nb-M2,3 are preferred for quantification. Different
      approaches are applied to improve the precision with regard to thickness-related
      errors. Thus, a precision up to +/-1.5% is achieved by averaging spectra from all
      three reference oxides to determine a k-factor using Nb-M4,5. Using the
      experimental k-factor, the determination of atomic concentration ratios CNb/CO in
      the range of 0.4 (Nb2O5) to 1 (NbO) was found to be possible with an accuracy of
      0.6% (relative deviation between measured and nominal composition), whereas
      ratios of calculated partial ionization cross sections lead to less accurate
      results.

PMID- 19852876
TI  - Different components of metacognition and their relationship to psychotic-like
      experiences.
AB  - BACKGROUND: Theories of the development of psychotic symptoms have suggested that
      metacognitive beliefs might play a part. However, studies offering supporting
      evidence have failed to distinguish between metacognitive beliefs about the
      consequences of having certain thoughts, and metacognitive beliefs about one's
      own cognitive skills. AIMS: To distinguish metacognitive beliefs and investigate
      the extent of their association with psychotic-like experiences. METHOD:
      Participants were 60 healthy adults recruited primarily from two university
      campuses. Three measures of metacognition were administered: (i) Metacognitions
      Questionnaire (MCQ-30); (ii) Metacognitive Assessment Inventory; and (iii) Koriat
      General Questions Test; and two schizotypy questionnaires: O-Life and SPQ-B and
      data were analysed using an exploratory principal components analysis of the
      metacognition measures. RESULTS: Three principal components were identified: (i)
      Beliefs about thoughts; (ii) Cognitive confidence; and (iii) Beliefs about
      cognitive regulation. Only the "beliefs about thoughts" component was
      significantly associated with the "psychotic-like experiences" factor, extracted
      from the measures of schizotypy. CONCLUSIONS: The finding supports theories
      suggesting that psychotic symptoms may be caused in part by negative
      metacognitive beliefs about thoughts. However, metacognition is a complex
      construct that is currently poorly understood.

PMID- 19852877
TI  - Learning the futility of the thought suppression enterprise in normal experience
      and in obsessive compulsive disorder.
AB  - BACKGROUND: The belief that we can control our thoughts is not inevitably
      adaptive, particularly when it fuels mental control activities that have ironic
      unintended consequences. The conviction that the mind can and should be
      controlled can prompt people to suppress unwanted thoughts, and so can set the
      stage for the intrusive return of those very thoughts. An important question is
      whether or not these beliefs about the control of thoughts can be reduced
      experimentally. One possibility is that behavioral experiments aimed at revealing
      the ironic return of suppressed thoughts might create a lesson that could reduce
      unrealistic beliefs about the control of thoughts. AIMS: The present research
      assessed the influence of the thought suppression demonstration on beliefs about
      the control of thoughts in a non-clinical sample, and among individuals with
      obsessive-compulsive disorder (OCD). METHOD: In Study 1, we assessed the effect
      of the thought suppression demonstration on beliefs about the control of thoughts
      among low and high obsessive individuals in the non-clinical population (N = 62).
      In Study 2, we conducted a similar study with individuals with OCD (N = 29).
      RESULTS: Results suggest that high obsessive individuals in the non-clinical
      population are able to learn the futility of suppression through the thought
      suppression demonstration and to alter their faulty beliefs about the control of
      thoughts; however, for individuals with OCD, the demonstration may be
      insufficient for altering underlying beliefs. CONCLUSIONS: For individuals with
      OCD, the connection between suppressing a neutral thought in the suppression
      demonstration and suppressing a personally relevant obsession may need to be
      stated explicitly in order to affect their obsessive beliefs.

PMID- 19852878
TI  - Brief CBT-I for insomnia comorbid with social phobia: A case study.
AB  - BACKGROUND: Despite an obvious link between social anxiety and acute state of
      insomnia, chronic types of sleep disturbances in people with social phobia have
      so far received limited research/clinical attention. This case report aims to
      illustrate the possibility of rectifying sleep disturbances comorbid with social
      phobia, using a brief cognitive behaviour therapy for insomnia (CBT-I). METHOD:
      Treatment involved five sessions of CBT-I provided individually on a weekly
      basis. Major treatment components included psychoeducation, sleep restriction
      therapy, stimulus control and cognitive restructuring. RESULTS: Treatment effects
      were assessed using sleep diary and questionnaires over the course of the
      treatment and at ~9 month follow-up. The results were encouraging with all
      targeted sleep parameters demonstrating improvements that met dual criteria for
      clinical significance. The gains were well maintained even at ~9 months after
      treatment. These improvements in sleep were accompanied by a reduction in sleep
      related anxiety and dysfunctional beliefs and attitudes about sleep. Whilst the
      patient also reported a corresponding improvement in daytime functioning and
      general anxiety, no gains were observed in depression and social anxiety.
      CONCLUSIONS: These findings highlight the potential benefits of incorporating
      brief CBT-I into existing treatments for social phobia and encourage further
      research on the intricate relationship between sleep, mood and social anxiety.

PMID- 19852879
TI  - Substudies of the Japan EPA Lipid Intervention Study (JELIS).

PMID- 19852880
TI  - Impact of circulating esterified eicosanoids and other oxylipins on endothelial
      function.
AB  - Eicosanoids, including epoxyeicosatrienoic acids, hydroxyeicosatetraenoic acids,
      and other oxylipins derived from polyunsaturated fatty acids, have emerging roles
      in endothelial inflammation and subsequent atherosclerosis. Unlike eicosanoids in
      the prostanoid series, they are known to be esterified in cell lipids such as
      phospholipids and triglycerides; however, our understanding of these reservoirs
      is in its infancy. This review focuses on recent work identifying circulating
      oxylipins, primarily esterified with lipoprotein lipids, and their effects on
      markers of endothelial dysfunction. These oxylipins are known to be released by
      at least one lipase (lipoprotein lipase) and to mediate increased expression of
      inflammatory markers in endothelial cells, which coincides with the known roles
      of lipoproteins in endothelial dysfunction. The implications of the lipolytic
      release of lipoprotein-bound oxylipins for the inflammatory response, challenges
      to analysis of this oxylipin compartment, and the potential importance of non
      arachidonate-derived oxylipins are discussed.

PMID- 19852881
TI  - The omega-3 index: from biomarker to risk marker to risk factor.
AB  - Blood levels of omega-3 fatty acids reflect the interplay of metabolism and the
      intake of omega-3-rich foods (eg, oily fish). Multiple lines of evidence link
      reduced tissue and/or blood levels of omega-3 fatty acids, as reflected in the
      erythrocyte eicosapentaenoic acid plus docosahexaenoic acid level (ie, the omega
      3 index), with increased risk for coronary heart disease, especially sudden
      cardiac death. The purpose of this review is to examine the extent to which
      biomarkers like the omega-3 index qualify as coronary heart disease risk markers
      and/or risk factors based on new criteria from the American Heart Association and
      older guidelines proposed in 1965 by Sir Austin Bradford Hill. These standards
      include consistency, strength of association, biological plausibility, coherence,
      dose-response relationship, clinical utility, cost effectiveness, and prospective
      validation. The omega-3 index appears to fulfill many of the requirements for a
      risk marker and, more importantly, for a risk factor.

PMID- 19852882
TI  - Dietary cholesterol and coronary artery disease: a systematic review.
AB  - Coronary heart disease (CHD) remains one of the leading causes of death in the
      United States and other industrialized nations. A better understanding of
      modifiable risk factors for CHD is critical in order to effectively prevent this
      disease. Dietary factors known to influence the risk of CHD include saturated
      fats, trans-fats, and polyunsaturated fatty acids. Although higher plasma levels
      of low-density lipoprotein cholesterol are associated with an increased risk of
      coronary disease and lipid-lowering therapy has been shown to reduce the risk of
      cardiovascular disease, the relation between dietary cholesterol and the risk of
      CHD is not clearly understood. This article reviews the current evidence on the
      association between dietary cholesterol and the risk of CHD.

PMID- 19852883
TI  - Trans-fatty acids and nonlipid risk factors.
AB  - Consumption of industrially produced trans-fatty acids (TFA) is associated with
      substantial risk of coronary heart disease (CHD). The magnitude of this
      relationship, as well as emerging associations with end points such as diabetes
      and sudden cardiac death, cannot be fully explained by the well-established
      adverse effects of TFA on serum lipids. We review the evidence for effects of TFA
      intake on nonlipid risk factors. Based on evidence from randomized controlled
      trials, observational studies, animal experiments, and in vitro studies, these
      include effects on systemic inflammation, endothelial dysfunction, visceral
      adiposity, insulin resistance, and arrhythmic risk. The types and strength of
      evidence for each of these nonlipid effects varies, but the overall constellation
      of findings is qualitatively and quantitatively unique among dietary fats. The
      multiple adverse effects and implicated pathways are consistent with the observed
      strong associations of TFA consumption with CHD risk. These nonlipid effects also
      explain why TFA consumption may adversely impact other non-CHD diseases and end
      points.

PMID- 19852884
TI  - Carotenoids and cardiovascular disease.
AB  - Carotenoids are a class of natural fat-soluble pigments found principally in
      plants. They have potential antioxidant biological properties due to their
      chemical structure and interaction with biological membranes. The most abundant
      carotenoids in the diet are beta-carotene, lycopene, lutein, beta-cryptoxanthin,
      zeaxanthin, and astaxanthin. Numerous epidemiologic studies have supported the
      hypothesis that antioxidants could be used as an inexpensive means of prevention,
      and possibly treatment, of cardiovascular diseases, even though findings from
      interventional trials have been mixed, with some positive findings, many null
      findings, and some suggestion of harm in certain high-risk populations. Recent
      smaller interventional studies with carefully chosen populations, such as those
      under high levels of oxidative stress, have yielded largely positive results.
      This suggests that we need more hypothesis-driven and rigorous clinical trial
      designs. The aim of this review is to examine the published studies about the use
      of carotenoids, especially lycopene and astaxanthin, in the treatment of
      cardiovascular diseases.

PMID- 19852885
TI  - Omega-3 fatty acids and heart failure.
AB  - During the past three decades, the protective role of omega (n)-3 polyunsaturated
      fatty acids (PUFA), mainly eicosapentaenoic acid and docosahexaenoic acid, in
      patients with coronary heart disease has been widely reported. The Gruppo
      Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure
      (GISSI-HF) study, a large-scale clinical trial, recently showed that n-3 PUFA
      (850-882 mg/d) reduced mortality and admission to the hospital for cardiovascular
      reasons in patients with chronic heart failure (HF) who were already receiving
      recommended therapies. The favorable effects of n-3 PUFA in GISSI-HF suggest that
      marine fish oils could confer protection in HF mainly through their
      antiarrhythmic action and in part by influencing the mechanisms related to HF
      progression. This article reviews recent clinical and experimental evidence on
      the effect of n-3 PUFA in coronary heart disease, with particular attention on HF
      and its pathophysiologic mechanisms.

PMID- 19852886
TI  - Cardiovascular disease-related genes and regulation by diet.
AB  - Diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as alpha
      linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are associated
      with decreased incidence and severity of cardiovascular disease (CVD). At least
      some of the beneficial effects of these dietary fatty acids are mediated by
      metabolites such as prostaglandins, leukotrienes, thromboxanes, and resolvins.
      The effects of n-3 PUFAs often differ from those of other fatty acids with very
      similar structures, such as linoleic acid and arachidonic acid (n-6 PUFAs) and
      their corresponding metabolites. This article reviews the evidence that specific
      receptors exist for fatty acids or their metabolites that are able to regulate
      gene expression and coordinately affect metabolic or signaling pathways
      associated with CVD. Four nuclear receptor subfamilies that respond to dietary
      and endogenous ligands and have implications for CVD are emphasized in this
      article: peroxisome proliferator-activated receptors, retinoid X receptors, liver
      X receptors, and the farnesoid X receptor.

PMID- 19852887
TI  - Vitamin D and cardiovascular disease.
AB  - Recent studies indicate that deficient vitamin D status may increase risk of both
      ischemic and nonischemic cardiovascular diseases independently of established
      cardiovascular risk factors. The role of vitamin D in potentially regulating many
      functions in the cardiovascular system is just beginning to be understood. Among
      the potentially relevant mechanisms for cardiovascular diseases, vitamin D may
      influence blood pressure through the renin-angiotensin system, parathyroid
      hormone levels, myocardial function, inflammation, and vascular calcification.
      Cardiovascular risk appears especially elevated at 25-hydroxy-vitamin D levels
      below 10 or 15 ng/mL, and optimal levels may be at least 30 ng/mL. Among
      individuals who are not receiving substantial exposure to sun, intakes of 1000 to
      2000 IU may be needed to achieve levels of at least 30 ng/mL. Further study,
      including properly designed randomized control trials, is required to further
      establish the role of vitamin D on cardiovascular diseases.

PMID- 19852888
TI  - Carbohydrate-restricted diets for obesity and related diseases: an update.
AB  - Basic, clinical, and epidemiologic research on carbohydrate-restricted dietary
      patterns continues to grow, evaluating the impact of this way of eating on weight
      loss, obesity-associated comorbidities, and development of any adverse effects.
      Randomized, controlled, dietary weight loss trials conducted in adults in the
      past 2 years reinforce previous findings that carbohydrate-restricted diets
      (CRDs) promote weight loss while increasing serum high-density lipoprotein
      cholesterol, lowering serum triglycerides, and improving glucose homeostasis.
      Studies showing that reduction of dietary carbohydrate leads to reduced
      postprandial serum glucose and insulin levels have spurred further research on
      CRDs in patients with type 2 diabetes. Emerging interest into the effect of diet
      on endothelial function has spawned studies that are harnessing new technologies,
      such as flow-mediated vascular dilation, to gain insight into the impact of diet
      on long-term cardiovascular disease outcomes. Studies on the effect of a CRD on
      appetite, health-related quality of life, bone density and turnover, acid-base
      metabolism, and potassium equilibrium help clinicians better weigh the perceived
      risks of the diet with the recognized benefits. This review synthesizes important
      clinical and physiologic studies on CRDs published between January 2007 and May
      2009.

PMID- 19852889
TI  - Nutritional supplements and serum lipids: does anything work?
AB  - Hyperlipidemia is a risk factor for the development of coronary heart disease.
      Many patients decline prescription lipid-lowering agents and opt instead for
      supplements. Before any supplement can be routinely recommended it is crucial to
      examine the types of clinical trials that have been performed, the mechanism by
      which a supplement is felt to alter lipids, the population studied, potential
      adverse effects, and the possibility that investigators might be biased. Clinical
      trial evidence strongly supports the notion that both red yeast rice and plant
      stanols and sterols effectively lower low-density lipoprotein (LDL) cholesterol.
      Preliminary evidence supports the possibility that green tea catechins and black
      tea theaflavins may lower LDL. Data do not support an LDL-lowering claim for
      guggulipid, policosanol, or cinnamon. Finally, there is strong clinical trial
      evidence suggesting that marine omega-3 fatty acids lower triglycerides.

PMID- 19852890
TI  - [Uniform format for disclosure of competing interests in the International
      Committee of Medical Journal Editors journals].

PMID- 19852891
TI  - [Obesity and health risk--what shall we measure?].

PMID- 19852892
TI  - [Measurement of body mass index and waist and hip circumference in adults].

PMID- 19852893
TI  - [Urinary incontinence during 12 years after delivery].
AB  - INTRODUCTION: First pregnancy and delivery often result in urinary incontinence.
      The aim of this 12-year cohort study was to estimate the impact of incontinence
      and the need for treatment. MATERIAL AND METHODS: A total of 305 women were
      questioned about lower urinary tract symptoms a few days, three months, five
      years and 12 years after their first delivery. RESULTS: A total of 242 women
      (79%) answered a questionnaire 12 years after their first delivery. Urinary
      incontinence increased significantly (p < 0.05) during the 12-year period to a
      total of 114 symptomatic women (47%); 25 of 102 women had stress incontinence
      (SI) and seven of 49 women had urge incontinence (UI) for at least 12 years.
      Three of 114 incontinent women (2.6%) had received treatment, while 162 women had
      exercised the pelvic floor the previous three months. None underwent SI surgery.
      Eighteen incontinent women wanted treatment; six of whom had SI alone and 12 of
      whom had both SI and UI. Among the 18 SI women ten had daily symptoms, while nine
      experienced social or hygienic inconvenience. Among the 86 incontinent women who
      did not want treatment, 51 had SI alone, 24 had both SI and UI, and 11 women had
      UI alone. Among the 75 SI women, five had daily symptoms, while ten experienced
      social or hygienic inconvenience. CONCLUSION: Urinary incontinence is prevalent
      12 years after first delivery, though few receive treatment. Incontinence
      severity is associated with a desire for treatment.

PMID- 19852895
TI  - [Walk-in spirometry pilot project for discovering of early chronic obstructive
      pulmonary disease].
AB  - INTRODUCTION: In Denmark, 10% of the health budget is spent on treating chronic
      obstructive lung disease (COPD) and the economic burden from COPD looks more than
      likely to grow in the near future. With this in mind we initiated a pilot project
      with The Danish Lung association to discover early stages of COPD by using
      spirometry. MATERIAL AND METHODS: A total of 344 persons from Aarhus and the
      surrounding area participated in a free anonymous walk-in spirometry project in
      the Health Centre, Aarhus. Among these, 291 persons were asked to fill in a
      questionnaire. A total of 135 smokers and/or persons with reduced lung function
      came to a second examination with yet another spirometry measurement and an
      advanced questionnaire. COPD staging was performed according to the GOLD and
      ERS/ATS criteria. RESULTS: 61% of the participants were women aged 60 years or
      older. 43% had normal lung function at the first examination. Only every fourth
      of those with COPD were aware of the fact that they had a lung disease. 33% would
      have visited their GP to have their lungs examined. 11-16% gave up smoking
      between the two examinations. CONCLUSION: This rather cost-effective walk-in
      design makes it possible to discover a substantial group of persons with
      previously unknown, mild and moderate COPD prior to examination and at the same
      time motivate people to give up smoking. Whether this is a long-term effect has
      yet to be determined.

PMID- 19852894
TI  - [Extraintestinal manifestations in inflammatory bowel disease].
AB  - Extraintestinal manifestations are relatively common in chronic inflammatory
      bowel disease and affect joints, skin, eyes and bile ducts. The most frequent
      rheumatologic manifestations are peripheral arthritis and axial arthropathies.
      Erythema nodosum and pyoderma gangraenosum are common dermatological
      manifestations, while episcleritis, iridocyclitis and uveitis are common
      ophthalmological complications. Conventional drugs and biologicals have proven
      effective in the treatment of several of the manifestations, including peripheral
      arthritis, pyoderma gangraenosum and episcleritis.

PMID- 19852896
TI  - [Status of the use of laboratory animals since 2000 in Denmark].
AB  - Since 2000 the annual use of laboratory animals in Denmark has remained constant
      at approx. 350,000 animals. Two thirds, i.e. approx. 220,000 of these, were used
      for medical research. The majority (48-69%) were used for research in
      neurological and psychiatric diseases, while 7-13% were used for cancer research,
      and 2-3% for cardiovascular research. The use of rabbits has declined since 2000,
      while the use of pigs is increasing.

PMID- 19852897
TI  - [Healthy obese subjects. Is weight loss treatment indicated?].
AB  - Recent studies have shown that about 20% of obese subjects are metabolically
      healthy with no increased risk for development of cardio-vascular disease or type
      2 diabetes. This group is characterized by normal metabolic parameters (do not
      have metabolic syndrome) and by minimal ectopic fat accumulation in the visceral
      depot, in the liver etc. It is argued that treatment intensity to obtain a weight
      loss should take the benign form of obesity into account since more active
      treatments such as pharmacotherapy and surgery may potentially be harmful rather
      than having a beneficial effect in this subgroup of obese subjects.

PMID- 19852898
TI  - [Delirium in the critically ill].
AB  - Interest in and the quantity of publications on delirium in critically ill
      patients have grown increasingly over the last decade. Critically ill patients
      have traditionally been sedated to facilitate mechanical ventilation. This
      practice impeded the recognition of delirium in the critically ill patients, and
      consequently the disorder was underdiagnosed. Delirium in the critically ill
      patients is associated with increased morbidity and mortality. Less sedation,
      guided by protocols with daily wake up trials, and validated delirium scoring
      systems, have improved the opportunities to diagnose and monitor delirium in the
      critically ill patients.

PMID- 19852899
TI  - [Cardiac arrest in child caused by button battery in the oesophagus and
      complicated by aorto-oesophageal fistula].
AB  - Ingestion of button battery can result in serious complications if the battery
      becomes lodged in the oesophagus. We report a case of a 14-month-old child who
      died from exanguination due to aorto-oesophageal fistula caused by a lithium
      button battery lodged in the oesophagus. Recommendations concerning diagnostics,
      treatment and observations are described.

PMID- 19852900
TI  - [Severe vitamin B12 deficiency in infants breastfed by vegans].
AB  - Weight loss and reduction of motor skills resulted in paediatric evaluation of a
      10-month-old girl and a 12-month-old boy. Both children suffered form anaemia and
      delayed development due to vitamin B12 deficiency caused by strict maternal vegan
      diet during pregnancy and nursing. Therapy with cyanocobalamin was instituted
      with remission of symptoms. Since infants risk irreversible neurologic damage
      following severe vitamin B12 deficiency, early diagnosis and treatment are
      mandatory. Vegan and vegetarian women should take vitamin B12 supplementation
      during the pregnancy and nursing period.

PMID- 19852901
TI  - [False-positive findings in screening for abdominal aortic aneurysm].
AB  - The incidence of false-positive screening results in connection with ultrasound
      scans (US) for abdominal aortic aneurysms (AAA) is unknown, but it is presumably
      a rare occurrence. The estimated predictive values of both false and true
      screening results are high because abdominal US describes the aortic diameter
      with a high precision. We describe a false-positive finding in a 66-year-old
      male. US abdominal screening led to a suspected 8.3 cm AAA. Consequently, a
      computed tomography was performed showing an AAA of normal proportions and a big
      bladder diverticulum in front of the aorta abdominalis.

PMID- 19852903
TI  - Current prescription patterns and safety profile of irreversible monoamine
      oxidase inhibitors: a population-based cohort study of older adults.
AB  - OBJECTIVE: To determine the prescription pattern and safety profile for
      irreversible monoamine oxidase inhibitors (MAOIs) in older adults over the past
      decade. METHOD: A population-based observational cohort study of older adults was
      conducted from January 1, 1997, to April 14, 2007, utilizing large administrative
      health care databases in Ontario, Canada. We examined the prevalence and
      incidence of irreversible MAOI use, as well as the frequency of coprescribing of
      MAOIs with contraindicated medications such as serotonergic and sympathomimetic
      drugs. We reviewed the most responsible diagnosis of emergency department (ED)
      visits and acute care admissions to assess for serious adverse events that may
      occur during MAOI treatment (ie, serotonin syndrome and hypertensive crisis).
      RESULTS: Over a 10-year period, there were 348 new users of irreversible MAOIs.
      The majority of patients showed a previous treatment pattern consistent with
      recurrent major depressive disorder, including prior use of antidepressant
      treatment and electroconvulsive therapy. The yearly incidence of MAOI
      prescriptions remained low and decreased from a rate of 3.1/100,000 to
      1.4/100,000. Concomitant exposure to at least 1 serotonergic drug occurred in
      18.1% of patients treated with an MAOI. No ED visits or acute care admissions for
      serotonin syndrome or hypertensive crisis were identified. CONCLUSIONS: The low
      prescription rate of MAOIs is not consistent with the continued recommendation of
      MAOIs by expert opinion leaders and consensus guidelines for use in atypical
      depression and treatment-refractory depression. While their use appeared safe,
      heightened awareness of the potential risk of concomitant use of serotonergic
      agents is necessary. Relative underuse of the MAOIs for a significant subgroup of
      depressed patients with atypical and treatment-refractory depression remains a
      concern.

PMID- 19852904
TI  - The efficacy of cognitive-behavioral therapy in bipolar disorder: a quantitative
      meta-analysis.
AB  - OBJECTIVE: The goal of the current study was to conduct a quantitative meta
      analysis investigating the role of cognitive-behavioral therapy (CBT) as
      adjunctive treatment to medication for patients diagnosed with bipolar disorder.
      DATA SOURCES: Studies included in the sample were identified through a computer
      search of articles in English in the MEDLINE database from January 1980 to March
      2008. Key terms entered were cognitive and bipolar disorder, cognitive therapy
      and bipolar disorder, cognitive behavioral therapy and bipolar disorder,
      psychotherapy and bipolar disorder, and psychosocial and bipolar disorder. STUDY
      SELECTION: Inclusion criteria were (1) randomized clinical trial investigating
      the role of adjunctive CBT in patients diagnosed with bipolar disorder, (2)
      clearly defined CBT intervention, (3) the inclusion of a control group, and (4)
      sufficient data reported to allow calculation of effect sizes. Twelve randomized
      clinical trials were selected for analysis on the basis of these criteria. DATA
      EXTRACTION: Effect sizes (Cohen d) were calculated according to published
      procedures. DATA SYNTHESIS: We found a low to medium overall effect size of CBT
      at posttreatment (d = -0.42, P < .05) and follow-up (d = -0.27, P < .05), and we
      found a positive impact of CBT on clinical symptoms (posttreatment d = -0.44, P <
      .05), cognitive-behavioral etiopathogenetic mechanisms (posttreatment d = -0.49,
      P < .05), treatment adherence (posttreatment d = -0.53, P < .05), and quality of
      life (posttreatment d = -0.36, P < .05). The impact was less evident in the case
      of relapse and/or recurrence (posttreatment d = -0.28). These effects on outcome
      categories were more evident at posttreatment compared to follow-up. CONCLUSIONS:
      Cognitive-behavioral therapy can be used as an adjunctive treatment to medication
      for patients with bipolar disorder, but new CBT strategies are needed to increase
      and enrich the impact of CBT at posttreatment and to maintain its benefits during
      follow-up.

PMID- 19852902
TI  - Loss of control over eating predicts outcomes in bariatric surgery patients: a
      prospective, 24-month follow-up study.
AB  - OBJECTIVE: This study examined the clinical significance of loss of control (LOC)
      over eating in bariatric surgery patients over 24 months of prospective,
      multiwave follow-ups. METHOD: Three hundred sixty-one gastric bypass surgery
      patients completed a battery of assessments before surgery and at 6, 12, and 24
      months following surgery. In addition to weight loss and LOC over eating, the
      assessments targeted eating disorder psychopathology, depression levels, and
      quality of life. The study was conducted between January 2002 and February 2008.
      RESULTS: Prior to surgery, 61% of patients reported general LOC; postsurgery, 31%
      reported LOC at 6-month follow-up, 36% reported LOC at 12-month follow-up, and
      39% reported LOC at 24-month follow-up. Preoperative LOC did not predict
      postoperative outcomes. In contrast, mixed models analyses revealed that
      postsurgery LOC was predictive of weight loss outcomes: patients with LOC
      postsurgery lost significantly less weight at 12-month (34.6% vs 37.2% BMI loss)
      and 24-month (35.8% vs 39.1% BMI loss) postsurgery follow-ups. Postsurgery LOC
      also significantly predicted eating disorder psychopathology, depression, and
      quality of life at 12- and 24-month postsurgery follow-ups. CONCLUSIONS:
      Preoperative LOC does not appear to be a negative prognostic indicator for
      postsurgical outcomes. Postoperative LOC, however, significantly predicts poorer
      postsurgical weight loss and psychosocial outcomes at 12 and 24 months following
      surgery. Since LOC following bariatric surgery significantly predicts attenuated
      postsurgical improvements, it may signal a need for clinical attention.

PMID- 19852905
TI  - Generalizability of the results of efficacy trials in first-episode
      schizophrenia: comparisons between subgroups of participants of the European
      First Episode Schizophrenia Trial (EUFEST).
AB  - OBJECTIVE: Most randomized drug trials in schizophrenia exclude patients with
      comorbidities such as suicidality or substance use, which may limit the
      generalizability of the results. We aimed to evaluate the generalizability of the
      results of these trials in participants of a randomized clinical trial with broad
      inclusion criteria. METHOD: In 50 sites in 14 countries, 498 patients with first
      episode psychosis (DSM-IV schizophrenia, schizoaffective disorder, or
      schizophreniform disorder) were recruited between December 2002 and January 2006
      in an open, randomized clinical drug trial with 12 months of follow-up. Baseline
      characteristics and follow-up data were compared between patients with versus
      patients without baseline suicidality and/or substance use. RESULTS: Of the 489
      participants with data on baseline suicidality and substance use, 153 (31%)
      patients were suicidal and/or using substances. Groups differed on only a few of
      the many baseline characteristics tested: comorbid patients were younger (25.1 vs
      26.5 years of age; P < .01), less often female (25% vs 47%; P < .001) or married
      (4% vs 17%; P < .001), had fewer years of education (11.8 vs 12.8; P < .001), and
      experienced lower levels of overall psychosocial functioning (Global Assessment
      of Functioning; 38.4 vs 40.8; P <or= .05) and higher levels of depression
      (Calgary Depression Scale for Schizophrenia; 6.1 vs 4.6; P < .001). At follow-up,
      comorbid patients showed shorter time to (re)hospitalization and reported higher
      levels of depression than patients without comorbidity (hazard ratio = 2.02, P =
      .004; chi(2)(7) = 17.25, P = .016, respectively), without differences on other
      outcome measures. CONCLUSIONS: Although it appears that the generalizability of
      antipsychotic treatment trials in first-episode patients is not seriously
      affected by the exclusion of patients with suicidal symptoms and/or substance
      use, researchers should be cautious about the exclusion of such patients. TRIAL
      REGISTRATION: controlled-trials.com Identifier: ISRCTN68736636.

PMID- 19852907
TI  - [Carcinoma of unknown origin: are we closer to finding that origin?].

PMID- 19852906
TI  - Risk factors for the development of posttraumatic stress disorder following
      combat trauma: a semiprospective study.
AB  - OBJECTIVE: When positioned in a combat situation, soldiers may be subjected to
      extreme stress. However, only a few combat-exposed soldiers develop long-term
      disturbance, namely, posttraumatic stress disorder (PTSD). This study aimed to
      explore risk factors for developing PTSD in order to improve the psychiatric
      screening process of new recruits. METHOD: In a semiprospective design, we
      compared 2,362 war veterans who developed PTSD (according to DSM-IV criteria)
      with an equal number of war veterans who did not develop PTSD. Controls were
      matched on the basis of sequential army identification numbers, that is, the
      soldier drafted immediately after the index PTSD veteran (usually on the same
      day). This method ensured similar demographic variables such as socioeconomic
      level and education. Data were collected from the Israeli Defense Force database
      and used in a comprehensive survey conducted between January 2000 and March 2001.
      Comparisons were made on predrafting personal factors (behavioral assessment,
      cognitive assessment, linguistic ability, and education) and pretrauma army
      characteristics (ie, rank and training). RESULTS: Neither behavioral assessment
      nor training were found to predict PTSD. The predictive factors that were found
      were essentially nonspecific, such as cognitive functioning, education, rank, and
      position during the trauma, with little effect from training. CONCLUSIONS: In an
      armed force that uses universal recruitment, carefully structured predrafting
      psychological assessment of social and individual qualifications (including
      motivation) failed to identify increased risk factors for PTSD. However,
      nonspecific factors were found to be associated with an increased risk for PTSD.
      This study suggests that the focus of future research on risk factors for PTSD
      should incorporate other domains rather than behavioral assessment alone. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00229359.

PMID- 19852908
TI  - [Time to first antibiotic dose in community-acquired pneumonia diagnosed in an
      emergency department].
AB  - BACKGROUND: Early antibiotic administration to patients diagnosed of community
      acquired pneumonia (CAP) has been associated with a lower mortality. In the USA,
      its administration within four hours has been implanted as a quality standard.
      The objective of this work was to analyze, in a Spanish emergency department, the
      performance with patients with CAP, focusing on the administration of the first
      dose of antibiotic. PATIENTS AND METHOD: Clinics, welfare and organizational
      aspects have been analysed on 93 patients diagnosed of CAP in an emergency
      department in order to identify their influence on antibiotic administration
      within 4 hours. RESULTS: 46.2% of patients received antibiotics within 4 hours.
      The fact that patients were assisted in the higher complexity level showed a
      positive association with the antibiotic administration within 4 hours. On the
      contrary, presence of more than 10 patients waiting to be admitted showed a
      negative association. CONCLUSIONS: Early antibiotic administration in the CAP is
      possible. On order to guarantee a higher number of patients taking antibiotics
      within 4 hours we have to improve quality of care in both the emergency
      department (to guarantee correct classification according to the level of
      complexity) and in the hospital (management of beds to avoid delay in the
      admission of the patients).

PMID- 19852909
TI  - [LDL-cholesterol goals and changes in C reactive protein in high coronary risk
      patients].
AB  - INTRODUCTION: We performed this study to compare the achievement of lipid targets
      as well as the change on C reactive protein (CRP) values of two different
      strategies, the combination of ezetimibe plus statins compared to the doubling of
      the previous statin dose. METHODS: Retrospective longitudinal study of 111
      dyslipidemic patients, treated with statins, whose cholesterol values were still
      elevated. In 59 patients the previous statin dose was doubled, in 52 patients
      ezetimibe was added to the statin. Differences on lipid parameters and CRP were
      measured. RESULTS: Patients treated with the association of ezetimibe plus
      statins obtained a higher reduction of LDL-cholesterol levels (38% vs. 18.1%,
      p<0.001), compared with those doubling the statin dose. A reduction on CRP values
      was observed only in patients on combined therapy (22.5%; p<0.005), CRP change
      was not related to lipids variation. More patients with high coronary risk
      treated with ezetimibe plus statin, reached lipid goals (LDL<100 mg/dl) compared
      to those whose statin dose was doubled (47% vs 19%; p<0.001) and the same
      happened on very high coronary risk patients (LDL<70 mg/dl) (43% vs 2%; p<0,001).
      More patients in the group ezetimibe plus statin achieved the combined target
      lipid control and CRP<3 mg/l (19% vs. 3%, p=0.002). DISCUSSION: Combination
      treatment of ezetimibe with statins on high coronary risk patients showed a
      better achievement of LDL-cholesterol goals with a reduction of CRP values.

PMID- 19852911
TI  - [Vertebral osteomyelitis caused by Streptococcus agalactiae in healthy adults.
      Description of 2 new cases].
AB  - The importance of Streptococcus agalactiae as a pathogen in nonpregnant adults
      has been widely recognized in recent years, especially in the elderly or
      immunocompromised patients. Two cases of vertebral osteomyelitis caused by S.
      agalactiae in young patients with no known underlying diseases or predisposing
      factor to infection are reported. A systematic review of the literature (MEDLINE,
      1976-May 2008) was performed, 10 cases previously reported in the literature of
      vertebral osteomyelitis due to S. agalactiae being found in adults under 65 years
      of age with no predisposing risk factors for infection, most of which have been
      reported over the last 10 years. We believe that this microbial etiology should
      be considered in patients of any age and immunological status. Other factors,
      other than increasing the number of patients with chronic diseases, explaining
      the increased rate of S. agalactiae infections in adults need to be studied.

PMID- 19852912
TI  - [Coronary calcification and subclinical myocardial dysfuncion in rheumatoid
      arthritis].
AB  - Rheumatoid arthritis (RA) is characterized by high cardiovascular (CV) mortality,
      which has been related to systemic inflammation. Our aim was to analyze coronary
      calcification by computed tomography and subclinical myocardial dysfunction
      evaluated by brain natriuretic peptide (BNP) levels and an electrocardiogram in
      RA patients and its relationship with disease characteristics. Seventy-three RA
      patients and same number of controls formed by osteoarthritis patients were
      studied, all without a background of cardiovascular clinical events. RA patients
      had a higher calcium score than the control group (19.2% vs. 11%; p=0.17)), this
      being associated with disease duration. BNP levels (90.0 vs. 45.4; p=0.003),
      corrected QT length, large QT frequency and silent myocardial infarct were higher
      in the RA group. In conclusion, RA patients showed more coronary calcification
      frequency than in general population and more biochemical and electrocardiogram
      myocardial subclinical dysfunction signs.

PMID- 19852913
TI  - [Therapeutic alternatives to CPAP in the sleep apnea-hypopnea syndrome.
      Scientific evidence].
AB  - Sleep apnea-hypopnea syndrome (SAPS) is a very prevalent disease in the general
      population.Its existence has been related with the appearance of cardiovascular
      and cerebrovascular events, greater risk of traffic accidents and deterioration
      of the quality of life of the patients.Currently, continuous positive airway
      pressure (CPAP) is the treatment of choice in SAPS. Although it is generally well
      tolerated and the side effects derived from its use are generally mild and
      transient, there are some patients who refuse it or do not tolerate it. Other
      alterative or complementary treatments should be offered to these patients.

PMID- 19852914
TI  - [Therapeutic management of cancer of unknown primary site by pathological types].
AB  - The term cancer of unknown primary site includes metastatic tumours with
      different histology and behaviour. Although most of them have a poor short-term
      prognosis, some patients can benefit from a treatment and will achieve a longer
      survival. The treatable cases are: metastases of squamous carcinoma in cervical
      or inguinal adenopathies, metastases of adenocarcinoma in axilar adenopathies in
      women, malignant ascites due to adenocarcinoma in women, osteoblastic bone
      metastases in men with elevated serum prostatic specific antigen levels, poorly
      differentiated tumours with features of a germinal extragonadal tumour, poorly
      differentiated neuroendocrine carcinomas and patients with a single metastasis.
      Chemotherapy must be considered in the rest of patients, although the optimum
      regimen is not well established yet.

PMID- 19852915
TI  - [59 year-old man with progressive renal failure, orbital pseudotumor, pericardial
      effusion and Raynaud phenomenon].

PMID- 19852916
TI  - [Acanthosis nigricans in 43 year old woman].

PMID- 19852917
TI  - [Pregnant women with complete atelectasia of the left lung and cardiac
      tamponade].

PMID- 19852918
TI  - [HCV-HIV coinfected woman with exercise dyspnea of 6 months course].

PMID- 19852919
TI  - [Abdominal muscle paralysis as a complication of herpes zoster].

PMID- 19852921
TI  - [Was I wrong in choosing internal medicine?].

PMID- 19852920
TI  - [Sinus histiocytosis sinusal with massive linphadenopathy (Rosai-Dorfman
      disease)].

PMID- 19852922
TI  - [Has improved the application of the European Society of Hypertension Guidelines
      2003 by physicians in Spain? Data from the PRETEND study].

PMID- 19852923
TI  - Feeding-associated gene expression in sheep scab mites (Psoroptes ovis).
AB  - The mite Psoroptes ovis is the causative agent of sheep scab. Although not
      usually fatal, the disease can spread rapidly and is a serious animal welfare
      concern. Vaccine development against ectoparasites has primarily focussed on two
      sources of candidate vaccine antigens - "exposed" antigens that are secreted in
      saliva during feeding on a host and "concealed" antigens that are usually
      expressed in the parasite gut and may be involved in digestion. Here, we sought
      to identify genes encoding proteins important for mite feeding and digestion by a
      subtractive suppressive hybridisation approach comparing mRNA transcript
      abundance in "fed" and "starved" mites. The study identified a variety of genes
      which are up-regulated by feeding mites. These included group 1, 5, 7 and 13
      allergens including the previously described cysteine protease Pso o 1. In
      addition, numerous novel genes were identified here including some encoding
      potential salivary gland proteins and others encoding proteins which may
      facilitate feeding such as a serum opacity factor. An olfactory receptor-like
      protein was identified in the starved mite population which may help the mite to
      identify a host.

PMID- 19852924
TI  - Optimization of time-resolved fluorescence assay for detection of europium
      tetraazacyclododecyltetraacetic acid-labeled ligand-receptor interactions.
AB  - Lanthanide-based luminescent ligand binding assays are superior to traditional
      radiolabel assays due to improving sensitivity and affordability in high
      throughput screening while eliminating the use of radioactivity. Despite
      significant progress using lanthanide(III)-coordinated chelators such as
      diethylenetriaminepentaacetic acid (DTPA) derivatives, dissociation-enhanced
      lanthanide fluoroimmunoassays (DELFIAs) have not yet been successfully used with
      more stable chelators (e.g., tetraazacyclododecyltetraacetic acid [DOTA]
      derivatives) due to the incomplete release of lanthanide(III) ions from the
      complex. Here a modified and optimized DELFIA procedure incorporating an acid
      treatment protocol is introduced for use with Eu(III)-DOTA-labeled peptides.
      Complete release of Eu(III) ions from DOTA-labeled ligands was observed using
      hydrochloric acid (2.0M) prior to the luminescent enhancement step. [Nle(4),d
      Phe(7)]-alpha-melanocyte-stimulating hormone (NDP-alpha-MSH) labeled with Eu(III)
      DOTA was synthesized, and the binding affinity to cells overexpressing the human
      melanocortin-4 (hMC4) receptor was evaluated using the modified protocol. Binding
      data indicate that the Eu(III)-DOTA-linked peptide bound to these cells with an
      affinity similar to its DTPA analogue. The modified DELFIA procedure was further
      used to monitor the binding of an Eu(III)-DOTA-labeled heterobivalent peptide to
      the cells expressing both hMC4 and cholecystokinin-2 (CCK-2) receptors. The
      modified assay provides superior results and is appropriate for high-throughput
      screening of ligand libraries.

PMID- 19852925
TI  - Influences of electrolytes and glucose on formulation of carbonate apatite
      nanocrystals for efficient gene delivery to mammalian cells.
AB  - Genetic manipulation of human cells through delivery of a functional gene or a
      gene-silencing element is an attractive approach to treat critical diseases very
      precisely and effectively. Extensive research on the genetic basis of human
      diseases with complete sequencing of human genome has revealed many vital genes
      as possible targets in gene therapy programs. On the other hand, to facilitate
      cell- or tissue-directed delivery of genes and gene-silencing nucleic acid
      sequences, both genetic and chemical engineering approaches have led to the
      generation of various viral and nonviral carriers. However, considering the
      issues of both safety and efficacy, none of the existing vectors is an ideal
      candidate for clinical use. We recently established pH-sensitive inorganic
      nanocrystals of carbonate apatite with capability of efficient intracellular
      delivery and release of associated DNA molecules for subsequent protein
      expression. Here we show a new synthetic approach for carbonate apatite crystals
      with stronger affinity toward DNA, leading to significant increment in both
      transgene delivery and expression. Moreover, CaCl(2) and NaCl, existing as the
      major electrolytes in the bicarbonate-buffered solution, dose-dependently govern
      particle size and eventually internalization and expression of particle
      associated DNA.

PMID- 19852926
TI  - Selective and facile assay of human immunodeficiency virus protease activity by a
      novel fluorogenic reaction.
AB  - A highly selective and facile assay of human immunodeficiency virus protease (HIV
      PR) has been required for the screening of medicinal inhibitors and also for
      classifying the subtypes of HIV in the therapeutic treatment of acquired immune
      deficiency syndrome (AIDS). This article describes a novel assay method of HIV-PR
      based on the selective fluorogenic reaction of peptides. A peptide fragment
      generated from a substrate by the enzymatic digestion with HIV-PR could be
      selectively quantified by the spectrofluorometric detection after the fluorogenic
      reaction with catechol in the presence of sodium periodate and sodium borate (pH
      7.0). This assay system uses an N-terminal acetyl peptide as the substrate and
      crude extracts from Escherichia coli expressing recombinant HIV-PR. The activity
      obtained by the proposed assay correlated with that obtained by a conventional
      HIV-PR assay based on fluorescence resonance energy transfer detection.

PMID- 19852927
TI  - Sublingual vaccination with outer membrane protein of Porphyromonas gingivalis
      and Flt3 ligand elicits protective immunity in the oral cavity.
AB  - In this study, we demonstrated that the 40-kDa outer membrane protein of
      Porphyromonas gingivalis (40k-OMP) sublingually administered with a cDNA vector
      plasmid encoding Flt3 ligand (pFL) elicited a protective immune response.
      Sublingual immunization of mice with 40k-OMP plus pFL induced significant serum
      IgG and IgA, as well as salivary IgA, antibody responses that were comparable to
      those induced by 40k-OMP plus cholera toxin as adjuvant. When the subclasses of
      40k-OMP-specific IgG were evaluated, sublingual immunization with 40k-OMP plus
      pFL induced both IgG1 and IgG2a antibody responses. Sublingual delivery of pFL
      resulted in FL expression in submandibular glands, but not in other oral tissues.
      Furthermore, marked increases in FL protein occurred in saliva and serum, and the
      frequencies of both CD11c(+)CD11b(+) and CD11c(+)CD8alpha(+) dendritic cells with
      up-regulated expression of CD80, CD86 and CD40 molecules significantly increased
      in submandibular lymph nodes and spleen. Importantly, the mice given sublingual
      40k-OMP plus pFL showed a significant reduction of alveolar bone loss caused by
      oral infection with P. gingivalis. These findings suggest that sublingual
      administration of 40k-OMP with pFL acts as an effective and safe mucosal vaccine
      against oral P. gingivalis infection, and may be a useful tool in the prevention
      of chronic periodontitis.

PMID- 19852928
TI  - Saturated fatty acids stimulate and insulin suppresses BMCP1 expression in bovine
      mammary epithelial cells.
AB  - Brain-specific uncoupling proteins such as uncoupling protein 4 (UCP4) and brain
      mitochondrial carrier protein 1 (BMCP1; also known as UCP5) were identified by
      computational analysis for expressed sequence tag and hybridization screening.
      Both were detected at the mRNA level by RT-PCR in cloned bovine mammary
      epithelial cells (bMEC) and lactating bovine mammary glands. Physiological
      concentrations of saturated fatty acids (stearate and palmitate), but not
      unsaturated fatty acids (oleate and linoleate), induced up-regulation of BMCP1
      mRNA in bMEC. Treatment with insulin induced down-regulation of UCP4 and BMCP1.
      These results suggest that UCP4 and BMCP1 are regulated by insulin and/or fatty
      acids in mammary epithelial cells and lactating mammary glands, and thereby may
      play an important role in lipid and energy metabolism.

PMID- 19852929
TI  - TRESK channel as a potential target to treat T-cell mediated immune dysfunction.
AB  - In this review, we propose that TRESK background K(+) channel could serve as a
      potential therapeutic target for T-cell mediated immune dysfunction. TRESK has
      many immune function-related properties. TRESK is abundantly expressed in the
      thymus, the spleen, and human leukemic T-lymphocytes. TRESK is highly activated
      by Ca(2+), calcineurin, acetylcholine, and histamine which induce hypertrophy,
      whereas TRESK is inhibited by immunosuppressants, such as cyclosporin A and
      FK506. Cyclosporine A and FK506 target the binding site of nuclear factor of
      activated T-cells (NFAT) to inhibit calcineurin. Interestingly, TRESK possesses
      an NFAT-like docking site that is present at its intracellular loop. Calcineurin
      has been found to interact with TRESK via specific NFAT-like docking site. When
      the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK.
      The activation of both TRESK and NFAT via Ca(2+)-calcineurin-NFAT/TRESK pathway
      could modulate the transcription of new genes in addition to regulating several
      aspects of T-cell function.

PMID- 19852930
TI  - Association of caspase-8 mutation with chemoresistance to cisplatin in HOC313
      head and neck squamous cell carcinoma cells.
AB  - Caspase-8 is a critical upstream mediator of apoptosis in the death receptor
      pathway. However, the relationship between caspase-8 mutation and
      chemosensitivity remain unclear in head and neck squamous cell carcinoma (HNSCC)
      carrying p53 mutation. In this study, we identified a caspase-8 nonsense
      mutation, accompanied by the loss of the second allele, in a drug-resistant
      HOC313 HNSCC cell line. The nonsense mutation (R68X) leads to truncation of all
      defined functional domains. Reconstitution of caspase-8 by stable transfection of
      wild-type caspase-8 sensitized the cells to cisplatin-, but not etoposide-induced
      apoptosis. Consistent with this, cisplatin, but not etoposide, induced TNF-alpha
      and TRAIL mRNA in caspase-8 reconstituted HOC313 cells, accompanied by activation
      of the reconstituted caspase-8 and its downstream caspase-3. These results
      indicate that the loss of caspase-8 plays an important role in acquisition of
      chemoresistance to cisplatin in HOC313 cells.

PMID- 19852931
TI  - Channel beta2-4 subunits fail to substitute for beta1 in sensitizing BK channels
      to lithocholate.
AB  - Large conductance, calcium- and voltage-gated potassium (BK) channels regulate
      numerous physiological processes. While most basic functional characteristics of
      native BK channels are reproduced by BK alpha (slo1) subunit homotetramers, key
      biophysical and pharmacological properties are drastically modified by the
      presence of auxiliary beta subunits (encoded by KCNMB1-4). Numerous physiological
      steroids, including sex hormones, gluco- and mineralocorticoids, activate beta
      subunit-containing BK channels, yet these steroids appear to be sensed by
      different types of beta subunits, with some steroids being sensed by homomeric
      slo1 channels as well. We recently showed that beta1 sensitizes the BK channel to
      microM concentrations of lithocholate (LC). Following expression of rat cerebral
      artery myocyte slo1 subunits ("cbv1") with beta1, beta2, beta3 or beta4 in
      Xenopus laevis oocytes we now demonstrate that BK beta2, beta3 and beta4 subunits
      fail to substitute for beta1 in providing LC-sensitivity (150 microM) to the BK
      channel. These findings document for the first time a rather selective steroid
      activation of BK channels via a particular channel accessory subunit. In
      addition, LC routinely activated native BK channels in myocytes freshly isolated
      from rat cerebral artery smooth muscle, where BK beta1 is highly expressed, while
      failing to do so in skeletal (flexor digitorum brevis) muscle, where BK beta1
      expression is negligible. This indicates that the native environment of the BK
      channel sustains the LC-sensitivity distinctly provided to the BK channel by
      beta1 subunits. Our study indicates that LC represents a unique tool to probe the
      presence of functional beta1-subunits and selectively activate BK channels in
      tissues that highly express KCNMB1.

PMID- 19852932
TI  - An efficient gene-disruption method in Cryptococcus neoformans by double-joint
      PCR with NAT-split markers.
AB  - Targeted gene disruption via biolistic transformation and homologous
      recombination is a method widely used to identify and investigate the function of
      genes in Cryptococcus neoformans that causes fatal fungal meningitis if not
      timely treated. Currently, most laboratories employ the overlap-PCR method to
      generate a gene-disruption cassette with dominant selectable markers, such as
      nourseothricin acetyltransferase (NAT). However, the conventional overlap-PCR
      method is often found to be inefficient because of the presence of multiple
      templates and of the long length of the final overlap-PCR products. In this
      report, we suggested an efficient gene-disruption method for C. neoformans,
      termed a double-joint PCR with NAT-split markers. Here we demonstrated that the
      gene-disruption cassette generated using double-joint PCR with NAT-split markers
      can be used successfully for targeted C. neoformans gene disruption with the
      advantages of providing a more convenient construction of gene-disruption
      cassettes and high targeted-integration frequency.

PMID- 19852933
TI  - The TryPIKinome of five human pathogenic trypanosomatids: Trypanosoma brucei,
      Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania
      infantum--new tools for designing specific inhibitors.
AB  - Phosphatidylinositol (PI) kinases are at the heart of one of the major pathways
      of intracellular signal transduction. Herein, we present the first report on a
      survey made by similarity searches against the five human pathogenic
      trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, Leishmania major,
      Leishmania braziliensis and Leishmania infantum genomes available to date for
      phosphatidylinositol- and related-kinases (TryPIKs). In addition to generating a
      panel called "The TryPIKinome", we propose a model of signaling pathways for
      these TryPIKs. The involvement of TryPIKs in fundamental pathways, such as
      intracellular signal transduction and host invasion processes, makes the study of
      TryPIKs an important area for further inquiry. New subtype-specific inhibitors
      are expected to work on individual members of the PIK family and, therefore, can
      presumably neutralize trypanosomatid invasion processes.

PMID- 19852934
TI  - Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS.
AB  - With a view toward improving delivery of exogenous glial cell line-derived
      neurotrophic factor (GDNF) to CNS motor neurons in vivo, we evaluated the
      bioavailability and pharmacological activity of a recombinant GDNF:tetanus toxin
      C-fragment fusion protein in mouse CNS. Following intramuscular injection,
      GDNF:TTC but not recombinant GDNF (rGDNF) produced strong GDNF immunostaining
      within ventral horn cells of the spinal cord. Intrathecal infusion of GDNF:TTC
      resulted in tissue concentrations of GDNF in lumbar spinal cord that were at
      least 150-fold higher than those in mice treated with rGDNF. While levels of
      immunoreactive choline acetyltransferase and GFRalpha-1 in lumbar cord were not
      altered significantly by intrathecal infusion of rGNDF, GDNF:TTC, or TTC, only
      rGDNF and GDNF:TTC caused significant weight loss following
      intracerebroventricular infusion. These studies indicate that insect cell-derived
      GDNF:TTC retains its bi-functional activity in mammalian CNS in vivo and improves
      delivery of GDNF to spinal cord following intramuscular- or intrathecal
      administration.

PMID- 19852935
TI  - PIKfyve upregulates CFTR activity.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      activated Cl(-) channel critically important in Cl(-) secreting epithelia.
      Mutations in the CFTR gene, such as (DeltaF508)CFTR leads to cystic fibrosis, a
      severe disease with defective Cl(-) secretion. CFTR is stimulated by the serum
      and glucocorticoid-inducible kinase SGK1. The SGK1 dependent regulation of
      several carriers and channels involves the phosphatidylinositol-3-phosphate-5
      kinase PIKfyve, which similarly mediates the regulation of glucose carriers by
      PKB/Akt. The present study was thus performed to elucidate whether PKB/Akt and
      PIKfyve are regulators of CFTR. To this end CFTR or (DeltaF508)CFTR were
      expressed in Xenopus oocytes alone or together with PKB, PIKfyve or the SGK1/PKB
      resistant mutant (S318A)PIKfyve, and the current generated by cAMP upregulation
      with 10muM forskolin+1mM IBMX determined utilizing dual electrode voltage clamp.
      As a result, forskolin/IBMX treatment triggered a current (I(cAMP)) in CFTR
      expressing Xenopus oocytes, but not in oocytes expressing (DeltaF508)CFTR.
      Coexpression of PKB/Akt and PIKfyve, but not of (S318A)PIKfyve, stimulated
      I(cAMP) in CFTR-expressing ( approximately 2- to 3-fold) but not in
      (DeltaF508)CFTR-expressing or water injected Xenopus oocytes.
      Immunohistochemistry revealed that the coexpression of PIKfyve, but not of
      (S318A)PIKfyve, enhanced the CFTR protein abundance but not the (DeltaF508)CFTR
      protein abundance in CFTR or (DeltaF508)CFTR-expressing oocytes. The present
      observations reveal a novel powerful regulator of intact but not of defective
      CFTR.

PMID- 19852936
TI  - Fibrinogen, fibrin, and FDP induce C-reactive protein generation in rat vascular
      smooth muscle cells: pro-inflammatory effect on atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease in the vessel. As an
      inflammatory cytokine, C-reactive protein (CRP) participates in the pathogenesis
      of atherosclerosis through multiple bioactivities. It has been widely accepted
      that hyperfibrinogenemia is associated with the formation and progression of
      atherosclerosis. But, it is unknown whether fibrinogen exerts a pro-inflammatory
      effect on vascular smooth muscle cells (VSMCs). The purpose of the present study
      was to observe the effect of fibrinogen, fibrin, and fibrin degradation products
      (FDP) on CRP generation in VSMCs. CRP mRNA expression was identified with the
      reverse transcription polymerase chain reaction. CRP level in the supernatant of
      VSMCs was measured with the enzyme-linked immunosorbent assay. CRP expression in
      VSMCs was examined with the immunocytochemical method. The results showed that
      fibrinogen, fibrin, and FDP all induced CRP production in VSMCs both in mRNA
      level and in protein level in a time- and concentration-dependent manner. The
      potency is FDP>fibrin>fibrinogen, which seems to mean that their pro-inflammatory
      activity decreases with increase of molecular weight of these three proteins. The
      finding provides a new mechanism for atherogenic effect of fibrin(ogen) and FDP,
      and emphasizes the importance of therapy of hyperfibrinogenemia in
      atherosclerosis.

PMID- 19852938
TI  - Nesfatin-1 evokes Ca2+ signaling in isolated vagal afferent neurons via Ca2+
      influx through N-type channels.
AB  - Nesfatin-1, processed from nucleobindin 2, is an anorexigenic peptide expressed
      in the brain and several peripheral tissues including the stomach and pancreas.
      Peripheral, as well as intracerebroventricular, administration of nesfatin-1
      suppresses feeding behavior, though underlying mechanisms are unknown. In this
      study, we examined effects of nesfatin-1 on cytosolic Ca(2+) concentration
      ([Ca(2+)](i)) in the neurons isolated from the vagal afferent nodose ganglion of
      mice. Nesfatin-1 at 10(-10)-10(-8)M increased [Ca(2+)](i) in the isolated neurons
      in a concentration-dependent manner, and at 10(-8)M it increased [Ca(2+)](i) in
      33 out of 263 (12.5%) neurons. These responses were inhibited under Ca(2+)-free
      conditions and by N-type Ca(2+) channel blocker, omega-conotoxin GVIA. All the
      nesfatin-1-responsive neurons also exhibited [Ca(2+)](i) responses to capsaicin
      and cholecystokinin-8. These results provide direct evidence that nesfatin-1
      activates vagal afferent neurons by stimulating Ca(2+) influx through N-type
      channels, demonstrating the machinery through which peripheral nesfatin-1 can
      convey signals to the brain.

PMID- 19852937
TI  - Cell-free production of Gaussia princeps luciferase--antibody fragment
      bioconjugates for ex vivo detection of tumor cells.
AB  - Antibody fragments (scFvs) fused to luciferase reporter proteins have been used
      as highly sensitive optical imaging probes. Gaussia princeps luciferase (GLuc) is
      an attractive choice for a reporter protein because it is small and bright and
      does not require ATP to stimulate bioluminescence-producing reactions. Both GLuc
      and scFv proteins contain multiple disulfide bonds, and consequently the
      production of active and properly folded GLuc-scFv fusions is challenging. We
      therefore produced both proteins individually in active form, followed by
      covalent coupling to produce the intended conjugate. We used an Escherichia coli
      based cell-free protein synthesis (CFPS) platform to produce GLuc and scFv
      proteins containing non-natural amino acids (nnAAs) for subsequent conjugation by
      azide-alkyne click chemistry. GLuc mutants with exposed alkyne reactive groups
      were produced by global replacement of methionine residues in CFPS. Antibody
      fragment scFvs contained a single exposed azide group using a scheme for site
      specific incorporation of tyrosine analogs. Incorporation of tyrosine analogs at
      specific sites in proteins was performed using an engineered orthogonal tRNA-tRNA
      synthetase pair from an archaebacterium. The unique azide and alkyne side chains
      in GLuc and the antibody fragment scFv facilitated conjugation by click
      chemistry. GLuc-scFv conjugates were shown to differentiate between cells
      expressing a surface target of the scFv and cells that did not carry this marker.

PMID- 19852939
TI  - Identification of small-molecule HSF1 amplifiers by high content screening in
      protection of cells from stress induced injury.
AB  - Small molecule amplifiers of heat shock response have shown promising results in
      rescuing stress related injury through chaperone amplification. Herein, we report
      the results of a high content target-based primary screening of several known
      bioactive libraries. Screening resulted in the identification of three potent
      gedunin derivatives and a sappanone A derivative. Western blot results confirmed
      compound-induced activation of HSF1 and increased expression level of HSP70.
      These compounds rescued cells from cell death caused by proteasome inhibitor MG
      132 and RNAi knockdown of HSF1 significantly reversed the cytoprotective effects,
      confirming an HSF1-dependent mechanism of action. These HSF1 amplifiers were
      tested in two mammalian cell based models of Huntington's disease (HD) and found
      to improve survival. Therefore, these screening hits may have therapeutic
      potential for HD and possibly other protein conformational disorders.

PMID- 19852940
TI  - Response letter to comments on "Cyclodextrins promote protein aggregation posing
      risks for therapeutic applications".

PMID- 19852942
TI  - Cell-to-cell contact induces human adipose tissue-derived stromal cells to
      differentiate into urothelium-like cells in vitro.
AB  - Human adipose-derived stromal cells (hASCs) are capable of multi-lineage
      differentiation. Co-culture of stem cells with mature cells or tissues can drive
      their differentiation toward required lineages. We investigated whether direct
      cell-to-cell contact between hASCs and human UCs, or soluble signaling molecules,
      could induce the differentiation of hASCs into urothelium-like cells in vitro.
      hASCs were isolated from human subcutaneous adipose tissue and amplified in
      vitro. After labeled by green fluorescent protein, hASCs were cultured with human
      UCs in direct co-culture, indirect co-culture and conditioned culture,
      respectively. Two weeks later, expressions of specific urothelial differentiation
      markers were analyzed by RT-PCR and immunofluorescence. We found that hASCs in
      direct co-culture expressed urothelial-specific genes uroplakin Ib, uroplakin II
      and cytokeratin 18. However, uroplakin III gene was not detected during the
      experimental period. Additionally, uroplakin Ib and cytokeratin 18 were observed
      in differentiated hASCs by immunofluorescence. Notably, none of these markers
      were detected in hASCs cultured in indirect co-culture and conditioned culture.
      These findings suggest that direct cell-to-cell contact between hASCs and human
      UCs can induce the differentiation of hASCs along urothelial lineage.

PMID- 19852941
TI  - Purification and characterization of a novel salivary antimicrobial peptide from
      the tick, Ixodes scapularis.
AB  - A novel antimicrobial peptide was isolated from the saliva of the Lyme disease
      tick vector, Ixodes scapularis, henceforth designated as ISAMP (I. scapularis
      Antimicrobial Peptide). ISAMP was purified using a sequential method including
      ultra filtration, gel filtration and reverse-phase high performance liquid
      chromatography. The purified peak had a molecular weight of 5.3kDa by MALDI/TOF
      MS and its amino acid sequence, determined by Edman degradation was
      PDxGxPxxVKAGRxPxxSI. A BLASTP search revealed that the protein is a putative
      5.3kDa secreted protein (AAM93656) from I. scapularis. The predicted protein is
      composed of 69 amino acids with no conserved domain motifs. Purified ISAMP was
      found to have antimicrobial activities against bacteria. Gene expression studies
      were carried out to observe ISAMP expression in different tick tissues. RT-PCR
      results indicated that the gene was expressed in hemocytes, fat body and salivary
      gland but virtually no expression was observed in the midgut. ISAMP is only
      similar to other Ixodid tick proteins, thus it is a member of a unique family.

PMID- 19852943
TI  - Primary human colonic epithelial cells are transiently protected from anoikis by
      a Src-dependent mechanism.
AB  - Complete loss of cell anchorage triggers apoptosis in primary human colonic
      epithelial cells (CEC), a phenomenon known as anoikis. Besides the induction of
      pro-apoptotic events, activation of survival pathways was observed in detached
      intestinal epithelial cell lines, providing a transient apoptosis protection.
      However, nothing is known about molecular mechanisms protecting primary CEC from
      anoikis. In this study intact CEC crypts were isolated and kept in suspension, a
      condition which leads to the loss of cell-cell anchorage and induces anoikis. To
      reconstitute cell-cell contacts, cells were centrifuged to form cell aggregates.
      Induction of apoptosis was assessed by caspase-3 activity assay; activation of
      survival pathways was analyzed by Western blot. Immediately after loss of cell
      anchorage a rapid activation of survival proteins was observed before active
      caspase-3 could be detected. Src hyperactivation significantly contributed to
      transient protection from anoikis in CEC because its inhibition reversed the
      protecting effect of re-establishment of cell contacts. Basal levels of active
      Src in CEC from patients with inflammatory bowel disease were markedly reduced
      compared to control patients. These results demonstrate that loss of cell
      anchorage activates survival pathways in primary human CEC providing transient
      anoikis protection. Src is an important mediator of this mechanism and therefore
      constitutes a key regulatory molecule coordinating survival signals mediated by
      cell adhesion in primary human CEC.

PMID- 19852944
TI  - Direct injection of autologous mesenchymal stromal cells improves myocardial
      function.
AB  - Cell-based therapies have been employed with conflicting results. Whether direct
      injection of ex-vivo expanded autologous marrow stromal cells (MSCs) would
      improve the function of ischemic myocardium and enhance angiogenesis is not well
      defined. In a porcine model of chronic ischemia, MSCs were isolated and cultured
      for 4 weeks. Sixteen animals were random divided into two groups to receive
      either direct intramyocardial injection of autologous MSCs, or equal volumes and
      injections sites of saline. Cine MRI and epicardial echocardiography were
      performed just prior to the injections and again 6 weeks later at the time of
      sacrifice at which point tissue was also analyzed. Myocardial function as
      assessed by regional wall thickening (as measured by dobutamine stress
      echocardiograms) demonstrated a 40.9% improvement after cell treatment of the
      ischemic zone (p=0.016) whereas the saline treated animals only had a 3.7% change
      (p=0.82) compared to baseline. The left ventricular ejection fractions of MSC
      group showed 19.5% improvement from baseline 35.9+/-3.8% to 42.9+/-5.8%
      (p=0.049). Increased vascularity was found in the MSC group compared to controls
      (0.80+/-0.30 vs 0.50+/-0.19 capillary/myocyte ratio, p=0.018). Direct injection
      of autologous MSCs promotes angiogenesis and enhances the functional improvements
      following chronic myocardial ischemia. This suggests that the angiogenesis
      engendered by cell treatment may be physiologically meaningful by improving the
      contractility of ischemic myocardium.

PMID- 19852945
TI  - Discovery and evaluation of Escherichia coli nitroreductases that activate the
      anti-cancer prodrug CB1954.
AB  - Gene-directed enzyme prodrug therapy (GDEPT) aims to achieve highly selective
      tumor-cell killing through the use of tumor-tropic gene delivery vectors coupled
      with systemic administration of otherwise inert prodrugs. Nitroaromatic prodrugs
      such as CB1954 hold promise for GDEPT as they are readily reduced to potent DNA
      alkylating agents by bacterial nitroreductase enzymes (NTRs). Transfection with
      the nfsB gene from Escherichia coli can increase the sensitivity of tumor cells
      to CB1954 by greater than 1000-fold. However, poor catalytic efficiency limits
      the activation of CB1954 by NfsB at clinically relevant doses. A lack of
      flexible, high-throughput screening technology has hindered efforts to discover
      superior NTR candidates. Here we demonstrate how the SOS chromotest and
      complementary screening technologies can be used to evaluate novel enzymes that
      activate CB1954 and other bioreductive and/or genotoxic prodrugs. We identify the
      major E. coli NTR, NfsA, as 10-fold more efficient than NfsB in activating CB1954
      as purified protein (k(cat)/K(m)) and when over-expressed in an E. coli nfsA(
      )/nfsB(-) gene deleted strain. NfsA also confers sensitivity to CB1954 when
      expressed in HCT-116 human colon carcinoma cells, with similar efficiency to
      NfsB. In addition, we identify two novel E. coli NTRs, AzoR and NemA, that have
      not previously been characterized in the context of nitroaromatic prodrug
      activation.

PMID- 19852946
TI  - The macrostructural and microstructural abnormalities of corpus callosum in
      children with attention deficit/hyperactivity disorder: a combined morphometric
      and diffusion tensor MRI study.
AB  - The corpus callosum (CC) is one of focused target areas which may play an
      important role in the pathophysiology of attention deficit hyperactivity disorder
      (ADHD). Conventional structural magnetic resonance imaging (MRI) studies have
      revealed the macrostructural abnormalities of CC and its subdivisions in ADHD
      compared with controls. However, no study has examined the macrostructural and
      microstructural characteristics of the CC in the same ADHD group. In this study,
      MRI morphometric and diffusion tensor imaging (DTI) techniques were combined to
      explore the area and measure fractional anisotropy (FA) abnormality of CC and its
      seven subdivisions in children with ADHD. Twenty-eight boys with ADHD (13.3+/-1.5
      years) and 27 age- and gender- matched controls (13.2+/-0.9 years) were included.
      We co-registered individual structural MRI and DTI images manually and subdivided
      the midsagittal CC into seven subdivisions. The area and FA of the CC and its
      subdivisions were then compared between the patients and the matched controls.
      Results showed that ADHD had decreased area of entire CC, anterior middle-body,
      and isthmus. Meanwhile, reduced FA value of the isthmus was found in the ADHD
      group compared with the controls. Our study indicated that not only
      macrostructural abnormalities but also microstructural alterations in CC,
      especially in isthmus occurred in ADHD. The abnormality of the isthmus, the
      subdivision that contains the fibers connecting posterior regions of brain, may
      play an important role in the pathophysiology of ADHD and may be implicated in
      the disorders of attention.

PMID- 19852947
TI  - Oral supplementation of catalpol ameliorates diabetic encephalopathy in rats.
AB  - Diabetes mellitus can cause dysfunction of the central nervous system called
      "diabetic encephalopathy." Although insulin and various oral drugs are used to
      treat diabetes, they do not completely prevent the development of diabetic
      encephalopathy, and novel strategies for the prevention and treatment are
      urgently needed. Catalpol, an iridoid glycoside, has properties of anti
      inflammation, antioxidant and decreasing blood glucose level and thus has the
      possibility of treating diabetic encephalopathy. Therefore, the study was
      designed to investigate the effects of catalpol on diabetic encephalopathy in
      rats. A single dose of 65 mg/kg streptozotocin was injected intraperitoneally to
      induce diabetes. Intragastric infusion of catalpol was performed for 6 weeks with
      the doses of 10, 50 and 100 mg/kg, respectively. The Y-type maze test,
      biochemical measurement, Nissl staining and the terminal deoxynucleotidyl
      transferase-mediated UTP nick end labeling methods were used to evaluate the
      neuropathological changes and the effects of catalpol on diabetic rats. The
      results showed that streptozotocin-induced diabetes produced obvious neuron
      damage and cognitive dysfunction coupling with markedly increased oxidative
      stress in the brain. Long-term oral supplementation of catalpol improved neuronal
      injury and cognitive dysfunction by attenuating oxidative stress. The effects
      that catalpol could both increase the nerve growth factor concentration and
      decrease the blood glucose level were related with the function of defending
      against oxidative stress of catalpol. The study suggested that oral
      supplementation of catalpol might be a potential therapeutic strategy for the
      treatment and/or prevention of diabetic encephalopathy.

PMID- 19852948
TI  - G protein-coupled receptor kinase 5, overexpressed in the alpha-synuclein up
      regulation model of Parkinson's disease, regulates bcl-2 expression.
AB  - G protein-coupled receptor kinase 5 (GRK5) has been reported to accumulate in
      Lewy bodies (LBs), a histological hallmark of Parkinson's disease. Recent
      findings propose that GRK5 might function in Parkinson's disease via
      phosphorylation of alpha-synuclein, a major component of LBs. In this study, the
      changes of the expression levels of GRK5 and its possible effects in Parkinson's
      disease were evaluated in cell lines and transgenic mice model of alpha-synuclein
      overexpression. Both the expression levels of cytoplasmic and nuclear distributed
      GRK5 were induced an increase via alpha-synuclein overexpression in vivo and in
      vitro. The observations that the levels of alpha-synuclein phosphorylated at Ser
      129 (pS129-alpha-synuclein) remain unchanged despite the downregulation of GRK5
      by short hairpin ribonucleic acid (shRNA) transfection suggest that GRK5 is not
      the sole kinase involved in phosphorylating alpha-synuclein in Parkinson's
      disease. In addition, the findings that nuclear accumulation of GRK5 inhibits bcl
      2 transcription and expression, at least in part by enhancing histone deacetylase
      (HDAC) activity, show an unexpected role for nuclear GRK5 in the regulation of an
      apoptosis-related gene. The present study suggests that GRK5 may be extensively
      involved in the mechanism of Parkinson's disease.

PMID- 19852949
TI  - Effects of a structural analogue of salsolinol, 1-MeDIQ, on pituitary prolactin
      release and dopaminergic activity in the mediobasal hypothalamus in nursing
      sheep.
AB  - The prolactin release caused by salsolinol (a derivative of dopamine, DA) in rats
      could be prevented by its structural analogue 1-methyl-3,4-dihydroisoqinoline (1
      MeDIQ). To study the participation of salsolinol in the neural stimulatory
      mechanism of prolactin release in lactating sheep, we tested whether 1-MeDIQ,
      acting at the central nervous system (CNS) level, would diminish basal prolactin
      release and reduce prolactin surge induced by suckling. A series of
      intracerebroventricular (icv) infusions of 1-MeDIQ (5 x 60 microg/60 microl/30
      min, at 30-min intervals) were performed in nursing ewes (n=8) during the fifth
      week of lactation. Additionally, by combining these infusions with push-pull
      perfusion, we studied the concentration of dopaminergic components, i.e.,
      salsolinol, DA and 3,4-dihydroxyphenylacetic acid (DOPAC) within the infundibular
      nucleus/median eminence (IN/ME) in four of the ewes. Treatment with 1-MeDIQ
      significantly (P<0.001) reduced either the basal prolactin release during the non
      suckling period or the suckling-induced prolactin surge. Specifically, the
      suppressive effect occurred gradually, affecting both the duration and amplitude
      of the prolactin surge. In the control ewes, the perfusate salsolinol
      concentration increased significantly (P<0.001) during suckling, while in the
      ewes treated with 1-MeDIQ only vestigial amounts of this compound were found
      during the non-suckling period. No DA was detected in the perfusates collected
      from the IN/ME of control and 1-MeDIQ-treated groups and no significant
      differences were found in the DOPAC concentrations between these groups. In
      conclusion, 1-MeDIQ is able to inhibit prolactin secretion in lactating sheep,
      acting at the CNS level. In addition, one of the way of 1-MeDIQ action may be
      directed to the local salsolinol release within the mediobasal hypothalamus.

PMID- 19852951
TI  - Fronto-cerebellar circuits and eye movement control: a diffusion imaging
      tractography study of human cortico-pontine projections.
AB  - A possible role of the cerebellum in cognitive function might be revealed through
      its anatomical connections with specific regions of the cerebral cortex. To
      understand the kind of information transmitted between the cortex and cerebellum,
      we studied the connections from six subdivisions of frontal and prefrontal cortex
      using diffusion imaging tractography. Cortico-pontine fibers travel through the
      cerebral peduncles and reach the cerebellum by way of a synaptic link in the
      pontine nuclei. In 19 human data sets, we tracked connections between the
      cerebral peduncle and left hemispheric masks of the superior frontal gyrus (SFG),
      precentral gyrus (PcG), middle frontal gyrus (MFG), orbital frontal cortex, and
      two regions of inferior frontal gyrus, including pars opercularis and pars
      triangularis. Cortico-pontine fibers arose from the PcG, the caudal/medial SFG
      and a small region of the MFG in a majority of the subjects analyzed. While these
      regions do have known roles in cognitive and executive functions, all three are
      strongly associated with the planning and execution of eye movements. Connections
      from more ventral prefrontal cortex were negligible, indicating that these
      regions are only sparsely represented in the circuit. Based on this pattern of
      connectivity, it is likely that the prefrontal connections to the cerebellum are
      involved in covert motor operations and the control of eye movements.

PMID- 19852950
TI  - The association of catechol-O-methyltransferase genotype with the phenotype of
      women with eating disorders.
AB  - OBJECTIVE: The modern brain imaging studies in patients with eating disorders
      have shown that neurotransmitting regulation differs distinctly from control
      groups. These disturbances have involved serotonin and dopamine system can be
      inherited and conditioned by genes. The aim of this work has been the analysis of
      association between eating disorders of anorexia or bulimia type and two
      polymorphisms of COMT gene. The additional goal has been the analysis of
      correlation among chosen personality and psychological features of ED women with
      the research gene variations. METHODS: The group taken as research sample
      consisted of adult 103 women (mean age=22.45+/-3.8 years) suffered from serious
      ED with illness lasting minimum 12 months. According to ICD-10 criteria, 61 women
      were diagnosed as anorexia nervosa while as 42 bulimia nervosa. The control group
      consisted of 108 ethnically and age-matched women with excluded major psychiatric
      disorders. The study groups were filling up the Eating Disorders Inventory and
      the Temperament and Character Inventory. The genotype of catechol-O
      methyltransferase in two polymorphisms rs4633 (his102his) and rs4680 (val158met)
      was determined. RESULTS: The joined GGCT genotype increased the risk of having ED
      over fivefold and over sevenfold the risk of having bulimia. Also haplotype CT
      was found three times more often in ED women than in controls. Besides the
      homozygous genotypes, AACC and GGCC reduced substantially the relative risk of
      ED. The patients with the low activity COMT genotype scored higher in EDI scales
      ineffectiveness, drive for thinness and perfectionism. The high activity genotype
      was connected with underdeveloped features of character marked in the poor
      cooperativeness and the poor self-directedness. These connections among genotypes
      and character scales were more expressed in bulimia group.

PMID- 19852952
TI  - Sensitive detection of MPLW515L/K mutations by amplification refractory mutation
      system (ARMS)-PCR.

PMID- 19852953
TI  - Curve fitting approach for measurement of cellular osmotic properties by the
      electrical sensing zone method. II. Membrane water permeability.
AB  - In a companion paper, we demonstrated that dynamic range limitations can confound
      measurement of the osmotically inactive volume using electrical sensing zone
      instruments (e.g., Coulter counters), and presented an improved parameter
      estimation method in which a lognormal function was fit to the cell volume
      distribution to allow extrapolation beyond the bounds of the data. Presently, we
      have investigated the effect of dynamic range limitations on measurement of the
      cell membrane water permeability (L(p)), and adapted the lognormal extrapolation
      method for estimation of L(p) from transient volume data. An alternative strategy
      (the volume limit adjustment method, in which the measured isotonic volume
      distribution is used to generate model predictions for curve fitting, and the
      bounds of the dynamic range are adjusted such that extrapolation is not required)
      was also developed. The performance of these new algorithms was compared to that
      of a conventional parameter estimation method. The best-fit L(p) values from in
      vitro experiments with mouse insulinoma (MIN6) cells differed significantly for
      the different parameter estimation techniques (p<0.001). Using in silico
      experiments, the volume limit adjustment method was shown to be the most accurate
      (relative error 0.4+/-3.2%), whereas the conventional method underestimated L(p)
      by 19+/-2% for MIN6 cells. Parametric analysis revealed that the error associated
      with the conventional method was sensitive to the dynamic range and the width of
      the volume distribution. Our initial implementation of the lognormal
      extrapolation method also yielded significant errors, whereas accuracy of this
      algorithm improved after including a normalization scheme.

PMID- 19852954
TI  - The Zn finger protein Iguana impacts Hedgehog signaling by promoting
      ciliogenesis.
AB  - Hedgehog signaling is critical for metazoan development and requires cilia for
      pathway activity. The gene iguana was discovered in zebrafish as required for
      Hedgehog signaling, and encodes a novel Zn finger protein. Planarians are
      flatworms with robust regenerative capacities and utilize epidermal cilia for
      locomotion. RNA interference of Smed-iguana in the planarian Schmidtea
      mediterranea caused cilia loss and failure to regenerate new cilia, but did not
      cause defects similar to those observed in hedgehog(RNAi) animals. Smed-iguana
      gene expression was also similar in pattern to the expression of multiple other
      ciliogenesis genes, but was not required for expression of these ciliogenesis
      genes. iguana-defective zebrafish had too few motile cilia in pronephric ducts
      and in Kupffer's vesicle. Kupffer's vesicle promotes left-right asymmetry and
      iguana mutant embryos had left-right asymmetry defects. Finally, human Iguana
      proteins (dZIP1 and dZIP1L) localize to the basal bodies of primary cilia and,
      together, are required for primary cilia formation. Our results indicate that a
      critical and broadly conserved function for Iguana is in ciliogenesis and that
      this function has come to be required for Hedgehog signaling in vertebrates.

PMID- 19852955
TI  - Zip6-attenuation promotes epithelial-to-mesenchymal transition in ductal breast
      tumor (T47D) cells.
AB  - Breast cancer is associated with zinc (Zn) hyper-accumulation in breast tissue
      which is postulated to be potentiated by the over-expression of Zn importing
      proteins. Zip6 (LIV-1) over-expression has been documented in estrogen receptor
      positive (ER+) breast tumors. Anti-estrogens, such as fulvestrant, are typically
      prescribed for ER+ breast cancer and thus may play a role in modulating cellular
      Zn hyper-accumulation. Herein, we investigated the physiological relevance of
      Zip6 over-expression and the consequences of Zip6-attenuation in breast tumor
      cells as a mechanism in the development of anti-estrogen resistance. We
      documented that over-expression of Zip6 was associated with significantly higher
      cellular Zn levels in tumor cells compared with normal breast cells. Fulvestrant
      significantly reduced Zn accumulation in tumor cells, without robust effects on
      Zip6 protein abundance. Zip6-attenuation significantly reduced cellular Zn pools,
      which was associated with increased mitochondrial membrane potential (DeltaPsim)
      and decreased apoptotic stimuli (cytoplasmic cytochrome C release, caspase-3 and 
      9 activities). Importantly, decreased apoptosis significantly increased tumor
      colony formation in soft agar and was associated with reduced E-cadherin
      expression. Our data suggest that anti-estrogen treatment regulates Zn level and
      importantly verify that Zip6 over-expression is not an underlying mechanism
      initiating breast cancer, but in fact may play a "tumor-constraining" role.

PMID- 19852956
TI  - Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and
      migration.
AB  - Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell
      migration by regulating the organization of actin filaments. Previous results
      suggested that mutationally activated forms of the Rho GTPases can activate the
      Signal Transducer and Activator of Transcription-3 (Stat3), but the exact
      mechanism is a matter of controversy. We recently demonstrated that Stat3
      activity of cultured cells increases dramatically following E-cadherin
      engagement. To better understand this pathway, we now compared Stat3 activity
      levels in mouse HC11 cells before and after expression of the mutationally
      activated Rac1 (Rac(V12)), at different cell densities. The results revealed for
      the first time a dramatic increase in protein levels and activity of both the
      endogenous Rac and Rac(V12) with cell density, which was due to inhibition of
      proteasomal degradation. In addition, Rac(V12)-expressing cells had higher Stat3,
      tyrosine-705 phosphorylation and activity levels at all densities, indicating
      that Rac(V12) is able to activate Stat3. Further examination of the mechanism of
      Stat3 activation showed that Rac(V12) expression caused a surge in mRNA of
      Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of
      gp130, the common subunit of this family reduced Stat3 activity, indicating that
      these cytokines may be responsible for the Stat3 activation by Rac(V12). The
      upregulation of IL6 family cytokines was required for cell migration and
      proliferation induced by Rac(V12), as shown by gp130 knockdown experiments, thus
      demonstrating that the gp130/Stat3 axis represents an essential effector of
      activated Rac for the regulation of key cellular functions.

PMID- 19852957
TI  - Lymphocytic infiltration leads to degradation of lacrimal gland extracellular
      matrix structures in NOD mice exhibiting a Sjogren's syndrome-like exocrinopathy.
AB  - We previously reported that lacrimal glands (LGs) of male non-obese diabetic
      (NOD) mice, an established mouse model of autoimmune inflammatory LG disease that
      displays many features of human LGs in patients afflicted with Sjogren's syndrome
      (SjS), exhibit significant degradation of extracellular matrix (ECM) structures
      as well as increased expression of matrix metalloproteinases (MMPs). The purpose
      of the current study was to expand the spectrum of proteases identified, to
      clarify their probable origin as well as to identify the contribution of these
      changes to disease pathogenesis. We explored in depth the changes in ECM
      structures and ECM protease expression at the onset of disease (6 weeks) versus
      late stage disease (18 weeks) in male NOD mouse LGs, relative to LGs of age
      matched male NODscid, a severely immunocompromised congenic strain, and healthy
      BALB/c mice. LG tissues were examined using routine histological,
      immunohistochemical, Western Blot and gene expression analyses novel multiphoton
      imaging technologies. We further characterized the profile of infiltrating immune
      cells under each condition using flow cytometry. Our results show that the
      initial infiltrating cells at 6 weeks of age are responsible for increased MMP
      and cathepsin H expression and therefore initiate the LG ECM degradation in NOD
      mice. More importantly, NODscid mice exhibited normal LG ECM structures,
      indicating the lymphocytes seen in the LGs of NOD mice are responsible for the
      degradation of the LG ECM. The disease-related remodeling of LG ECM structures
      may play a crucial role in altering the acinar signaling environment, disrupting
      the signaling scaffolds within the cells, which are required to mobilize the
      exocytotic trafficking machinery, ultimately leading to a loss of LG function in
      patients afflicted with SjS.

PMID- 19852958
TI  - Teladorsagia circumcincta: survival of adults in vitro is enhanced by the
      presence of a mammalian cell line.
AB  - Adult Teladorsagia circumcincta survival and motility in vitro was examined in a
      range of different cell culture media, supplements and gas mixes. Under optimum
      conditions, worms survived for 14 days, exhibiting high motility for 9 days and
      egg production for 72 h. Optimum conditions involved co-culture of worms with a
      HeLa cell line in a supplemented cell medium (CEM) and an atmosphere containing
      10% CO(2), 5% O(2) 85% N(2), 65% humidity at 37 degrees C. The incubation medium
      consisted of Minimum Essential Medium with 10% fetal calf serum, 1% non-essential
      amino acids, 1% glutamax and 1% penicillin-neomycin-streptomycin cocktail mix.
      Compared with optimum conditions, incubation in CEM alone, cell conditioned CEM,
      RPMI alone, Medium 199 alone, reduced CO(2) or O(2), or when cells were replaced
      with Escherichia coli, both survival and motility were reduced. Optimum
      conditions for adult T. circumcincta maintenance for culture, anthelmintic
      testing or generation of excretory/secretory products are described.

PMID- 19852959
TI  - Significance of glycosphingolipid fatty acid chain length on membrane microdomain
      mediated signal transduction.
AB  - Lactosylceramide (LacCer), a neutral glycosphingolipid, is abundantly expressed
      on human neutrophils, and specifically recognizes several pathogenic
      microorganisms. LacCer forms membrane microdomains coupled with the Src family
      kinase Lyn on the plasma membrane, and ligand binding to LacCer activates Lyn,
      resulting in neutrophil functions. In contrast, neutrophilic differentiated HL-60
      cells do not have Lyn-associated LacCer-enriched microdomains and lack LacCer
      mediated functions. In neutrophil plasma membranes, the very long fatty acid
      C24:0 and C24:1 chains are the main components of LacCer, whereas plasma membrane
      of D-HL-60 cells mainly includes C16-LacCer species. Here, we suggest that LacCer
      species containing very long fatty acid chains are indispensable for the
      association of Lyn with LacCer-enriched microdomains and LacCer-mediated
      functions.

PMID- 19852960
TI  - A novel neural-specific BMP antagonist, Brorin-like, of the Chordin family.
AB  - We identified a gene encoding a novel secreted protein in mice, humans, and
      zebrafish. As the protein of 222 amino acids is similar to Brorin, a secreted BMP
      antagonist, which is a member of the Chordin family, we named it Brorin-like.
      Recombinant Brorin-like protein weakly but significantly inhibited the activity
      of BMP in mouse preosteoblastic cells and promoted neurogenesis in mouse neural
      precursor cells. Brorin-like was predominantly expressed in the adult brain and
      embryonic neural tissues. The inhibition of Brorin-like functions in zebrafish
      resulted in the impairment of neural development. Brorin-like potentially plays
      roles in neural development and functions.

PMID- 19852961
TI  - In vivo molecular imaging of colorectal cancer with confocal endomicroscopy by
      targeting epidermal growth factor receptor.
AB  - BACKGROUND & AIMS: Epidermal growth factor receptor (EGFR) is a therapeutic
      target for colorectal cancer (CRC). However, technical challenges have limited in
      vivo imaging of EGFR in CRCs. Confocal laser endomicroscopy (CLE) enables
      accurate microscopic visualization of CRC in patients during endoscopy. We
      evaluated the ability to use CLE in vivo for instantaneous molecular imaging of
      EGFR in CRC models. METHODS: Tumors were grown in mice (n = 68) from human CRC
      cell lines that expressed high (SW480 cells) or low (SW620 cells) levels of EGFR.
      Tumors were visualized in vivo with a handheld CLE probe after injection of
      fluorescently labeled EGFR antibodies. EGFR-specific fluorescence was graded from
      0 to 3+. Neoplastic and non-neoplastic specimens from human colorectal mucosa
      were examined. In vivo findings were correlated with histopathology,
      immunohistochemistry, and fluorescence microscopy analyses. RESULTS: CLE analysis
      of cell cultures confirmed the different expression levels of EGFR between cell
      lines. In living animals, CLE differentiated EGFR expression levels between tumor
      cell limes (mean fluorescence, 1.92 +/- 0.22 [SW480] and 0.59 +/- 0.21 [SW620], P
      = .0004). CLE analysis of EGFR expression in human specimens allowed distinction
      of neoplastic from non-neoplastic tissues (mean fluorescence, 2.0 +/- 0.37 vs
      0.25 +/- 0.16, respectively, P = .0035). CONCLUSIONS: CLE can be used for in
      vivo, molecular analysis of CRC and to differentiate EGFR expression patterns in
      xenograft tumors and human tissue samples. Because CLE can be performed during
      endoscopy, in vivo molecular imaging might be used in diagnosis of CRC and to
      predict response to targeted therapies.

PMID- 19852962
TI  - Rapid HCV-RNA decline with once daily TMC435: a phase I study in healthy
      volunteers and hepatitis C patients.
AB  - BACKGROUND & AIMS: The search for targeted anti-hepatitis C virus (HCV) drugs is
      driven by the adverse effect profile and limited efficacy of the current standard
      of care (pegylated interferon-alpha/ribavirin). In a first-in-human trial, we
      tested the safety, tolerability, and pharmacokinetics of the macrocyclic HCV
      NS3/4A protease inhibitor TMC435 in healthy volunteers, followed by HCV genotype
      1-infected patients to assess antiviral activity. METHODS: The TMC435350-C101
      study was a phase I, randomized, double-blind, placebo-controlled trial in 49
      healthy volunteers, followed by an open-label, nonplacebo-controlled panel in 6
      genotype 1 hepatitis C patients. Healthy volunteers received oral, single,
      ascending doses (up to 600 mg) or 5-day multiple ascending doses (200 mg twice
      daily or 100, 200, or 400 mg once daily). Patients received 200 mg once daily for
      5 days. Pharmacokinetics and safety were evaluated for all panels, and plasma HCV
      RNA levels were determined in patients. RESULTS: There were no serious adverse
      events, no grade 3 reactions, and no treatment-related discontinuations;
      pharmacokinetics supported a once daily dosing regimen. Plasma HCV-RNA levels
      dropped rapidly in all patients, with a median maximal reduction of 3.9-log(10)
      IU/mL and a median of 6 days to maximal reduction. The initial steep reduction of
      HCV-RNA (median 3.5-log(10) IU/mL at day 3) was followed by a more gradual
      decline that was maintained over the dosing period. No viral breakthroughs (>1
      log(10) IU/mL HCV-RNA increase from nadir) were observed during treatment nor in
      the 3 days posttreatment; HCV-RNA returned to pretreatment levels by week 4.
      CONCLUSIONS: Once daily TMC435 given orally was generally safe and well tolerated
      and demonstrated potent antiviral activity.

PMID- 19852963
TI  - Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early
      detection of hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The outcome of patients with hepatocellular carcinoma (HCC)
      remains poor because of late diagnosis. The aim of this study was to compare the
      accuracy of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in
      the early diagnosis of HCC. METHODS: Among 1031 patients randomized in the
      Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial, a
      nested case-control study of 39 HCC cases (24 early stage) and 77 matched
      controls was conducted to compare the performance of AFP and DCP. Testing was
      performed on sera from 12 months prior (month -12) to the time of HCC diagnosis
      (month 0). RESULTS: The sensitivity and specificity of DCP at month 0 was 74% and
      86%, respectively, at a cutoff of 40 mAU/mL and 43% and 100%, respectively, at a
      cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61%
      and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At
      month -12, the sensitivity and specificity at the low cutoff was 43% and 94%,
      respectively, for DCP and 47% and 75%, respectively, for AFP. Combining both
      markers increased the sensitivity to 91% at month 0 and 73% at month 12, but the
      specificity decreased to 74% and 71%, respectively. Diagnosis of early HCC was
      triggered by surveillance ultrasound in 14, doubling of AFP in 5, and combination
      of tests in 5 patients. CONCLUSIONS: Biomarkers are needed to complement
      ultrasound in the detection of early HCC, but neither DCP nor AFP is optimal.

PMID- 19852965
TI  - Tick-susceptible Bos taurus cattle display an increased cellular response at the
      site of larval Rhipicephalus (Boophilus) microplus attachment, compared with tick
      resistant Bos indicus cattle.
AB  - Cattle demonstrate divergent and heritable phenotypes of resistance and
      susceptibility to infestation with the cattle tick Rhipicephalus (Boophilus)
      microplus. Bos indicus cattle are generally more resistant to tick infestation
      than Bos taurus breeds although large variations in resistance can occur within
      subspecies and within breed. Increased tick resistance has been previously
      associated with an intense hypersensitivity response in B. taurus breeds;
      however, the mechanism by which highly resistant B. indicus cattle acquire and
      sustain high levels of tick resistance remains to be elucidated. Using the
      commercially available Affymetrix microarray gene expression platform, together
      with histological examination of the larval attachment site, this study aimed to
      describe those processes responsible for high levels of tick resistance in
      Brahman (B. indicus) cattle that differ from those in low-resistance Holstein
      Friesian (B. taurus) cattle. We found that genes involved in inflammatory
      processes and immune responsiveness to infestation by ticks, although up
      regulated in tick-infested Holstein-Friesian cattle, were not up-regulated in
      Brahman cattle. In contrast, genes encoding constituents of the extracellular
      matrix were up-regulated in Brahmans. Furthermore, the susceptible Holstein
      Friesian animals displayed a much greater cellular inflammatory response at the
      site of larval R. microplus attachment compared with the tick-resistant Brahman
      cattle.

PMID- 19852964
TI  - Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b
      plus ribavirin for treating chronic hepatitis C virus infection.
AB  - BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection are
      frequently treated with a combination of pegylated interferon (peginterferon) and
      ribavirin. This study compared the efficacy and safety of peginterferon alfa-2a
      and peginterferon alfa-2b, each in combination with ribavirin. METHODS: A total
      of 320 consecutive, treatment-naive, HCV RNA-positive patients with chronic
      hepatitis were randomly assigned to once-weekly peginterferon alfa-2a (180
      microg, group A) or peginterferon alfa-2b (1.5 microg/kg, group B) plus ribavirin
      1000 mg/day (body weight <75 kg) or 1200 mg/day (body weight >or=75 kg) for 48
      weeks (genotype 1 or 4) or 24 weeks (genotype 2 or 3). The primary end point was
      sustained virological response (SVR) by intention-to-treat. RESULTS: More
      patients in group A than group B achieved an SVR (110/160 [68.8%] vs 87/160
      [54.4%]; P = .008). Higher SVR rates were obtained in group A than group B among
      patients with genotype 1/4 (51/93 [54.8%] vs 37/93 [39.8%]; P = .04), with
      genotype 2/3 (59/67 [88.1%] vs 50/67 [74.6%]; P = .046), without cirrhosis
      (96/127 [75.6%] vs 75/134 [55.9%]; P = .005), and with baseline levels HCV RNA
      >500,000 IU/mL (58/84 [69%] vs 43/93 [46.2%]; P = .002). SVR rates in groups A
      and B were not statistically different among patients with baseline HCV RNA
      <or=500,000 IU/mL (52/76 [68.4%] vs 44/67 [65.7%]; P = .727) or in patients with
      cirrhosis (14/33 [42.4%] vs 12/26 [46.1%]; P = .774). CONCLUSIONS: In patients
      with chronic HCV infection, peginterferon alfa-2a plus ribavirin produced a
      significantly higher SVR rate than peginterferon alfa-2b plus ribavirin.

PMID- 19852966
TI  - Analysis of pupal head proteome and its alteration in diapausing pupae of
      Helicoverpa armigera.
AB  - The proteomic approach has proven to be an useful tool for understanding insect
      diapause processes. Using 2D gel electrophoresis and matrix assisted
      laser/desorption ionization (MALDI) time of flight (TOF), we identified 24
      proteins in the head of Helicoverpa armigera pupae with diverse functional
      characteristics, including cytoskeleton proteins, heat-shock proteins, insect
      development regulation factors, ATPases, proteins regulating signal pathway and
      enzymes involved in metabolism, etc. A proteomic comparison between nondiapausing
      and diapausing pupae revealed three proteins that were present only in
      nondiapausing pupae, and six proteins represented >or=2.0-fold or <or=0.5-fold
      changes. The differentially expressed proteins, including heat-shock protein 90,
      chitin deacetylase, alpha-tubulin and transitional endoplasmic reticulum ATPase,
      etc. were reported for the first time in H. armigera. Identification of these
      proteins will enable us to further characterize the regulated functions of
      diapause in this important species.

PMID- 19852967
TI  - Vibration receptive sensilla on the wing margins of the silkworm moth Bombyx
      mori.
AB  - Bristles along the wing margins (wm-bristles) of the silkworm moth, Bombyx mori,
      were studied morphologically and electrophysiologically. The male moth has ca. 50
      wm-bristles on each forewing and hindwing. Scanning electron microscopy revealed
      that these wm-bristles are typical mechanosensilla. Leuco-methylene blue staining
      demonstrated that each wm-bristle has a single receptor neuron, which is also
      characteristic of the mechanosensillum. The receptor neuron responded to
      vibrating air currents but did not respond to a constant air current. The wm
      bristles showed clear directional sensitivity to vibrating air currents. The wm
      bristles were classified into two types, type I and type II, by their response
      patterns to sinusoidal movements of the bristle. The neuron in type I discharged
      bursting spikes immediately following stimulation onset and also discharged a
      single spike for each sinusoidal cycle for frequencies less than ca. 60 Hz. The
      neuron in type II only responded to vibrations over 40 Hz and, specifically at 75
      Hz, discharged a single spike for each sinusoidal cycle throughout the
      stimulation period. These results suggest that the two types of wm-bristles are
      highly tuned in different ways to detect vibrations due to the wing beat. The
      roles of the wm-bristles in the wing beat are discussed.

PMID- 19852969
TI  - A model for all genomes: the role of transcription factories.
AB  - A model for all genomes involving one major architectural motif is presented: DNA
      or chromatin loops are tethered to "factories" through the transcription
      machinery-a polymerase (active or inactive) or its transcription factors
      (activators or repressors). These loops appear and disappear as polymerases
      initiate and terminate (and as factors bind and dissociate), so the structure is
      ever-changing and self-organizing. This model is parsimonious, detailed (and so
      easily tested), and incorporates elements found in various other models.

PMID- 19852968
TI  - FTY720 prevents ischemia/reperfusion injury-associated arrhythmias in an ex vivo
      rat heart model via activation of Pak1/Akt signaling.
AB  - Recent studies demonstrated a role of sphingosine-1-phosphate (S1P) in the
      protection against the stress of ischemia/reperfusion (I/R) injury. In
      experiments reported here, we have investigated the signaling through the S1P
      cascade by FTY720, a sphingolipid drug candidate displaying structural similarity
      to S1P, underlying the S1P cardioprotective effect. In ex vivo rat heart and
      isolated sinoatrial node models, FTY720 significantly prevented arrhythmic events
      associated with I/R injury including premature ventricular beats, VT, and sinus
      bradycardia as well as A-V conduction block. Real-time PCR and Western blot
      analysis demonstrated the expression of the S1P receptor transcript pools and
      corresponding proteins including S1P1, S1P2, and S1P3 in tissues dissected from
      sinoatrial node, atrium and ventricle. FTY720 (25 nM) significantly blunted the
      depression of the levels of phospho-Pak1 and phospho-Akt with ischemia and with
      reperfusion. There was a significant increase in phospho-Pak1 levels by 35%,
      199%, and 205% after 5, 10, and 15 min of treatment with 25 nM FTY720 compared
      with control nontreated myocytes. However, there was no significant difference in
      the levels of total Pak1 expression between nontreated and FTY720 treated.
      Phospho-Akt levels were increased by 44%, 63%, and 61% after 5, 10, and 15 min of
      treatment with 25 nM FTY720, respectively. Our data provide the first evidence
      that FTY720 prevents I/R injury-associated arrhythmias and indicate its potential
      significance as an important and new agent protecting against I/R injury. Our
      data also indicate, for the first time, that the cardioprotective effect of
      FTY720 is likely to involve activation of signaling through the Pak1.

PMID- 19852970
TI  - An enhanced system for unnatural amino acid mutagenesis in E. coli.
AB  - We report a new vector, pEVOL, for the incorporation of unnatural amino acids
      into proteins in Escherichia coli using evolved Methanocaldococcus jannaschii
      aminoacyl-tRNA synthetase(s) (aaRS)/suppressor tRNA pairs. This new system
      affords higher yields of mutant proteins through the use of both constitutive and
      inducible promoters to drive the transcription of two copies of the M. jannaschii
      aaRS gene. Yields were further increased by coupling the dual-aaRS promoter
      system with a newly optimized suppressor tRNA(CUA)(opt) in a single-vector
      construct. The optimized suppressor tRNA(CUA)(opt) afforded increased plasmid
      stability compared with previously reported vectors for unnatural amino acid
      mutagenesis. To demonstrate the utility of this new system, we introduced 14
      mutant aaRS into pEVOL and compared their ability to insert unnatural amino acids
      in response to three independent amber nonsense codons in sperm whale myoglobin
      or green fluorescent protein. When cultured in rich media in shake flasks, pEVOL
      was capable of producing more than 100 mg/L mutant GroEL protein. The
      versatility, increased yields, and increased stability of the pEVOL vector will
      further facilitate the expression of proteins with unnatural amino acids.

PMID- 19852971
TI  - Engineered cystine knot miniproteins as potent inhibitors of human mast cell
      tryptase beta.
AB  - Here we report the design, chemical and recombinant synthesis, and functional
      properties of a series of novel inhibitors of human mast cell tryptase beta, a
      protease of considerable interest as a therapeutic target for the treatment of
      allergic asthma and inflammatory disorders. These inhibitors are derived from a
      linear variant of the cyclic cystine knot miniprotein MCoTI-II, originally
      isolated from the seeds of Momordica cochinchinensis. A synthetic cyclic
      miniprotein that bears additional positive charge in the loop connecting the N-
      and C-termini inhibits all monomers of the tryptase beta tetramer with an overall
      equilibrium dissociation constant K(i) of 1 nM and thus is one of the most potent
      proteinaceous inhibitors of tryptase beta described to date. These cystine knot
      miniproteins may therefore become valuable scaffolds for the design of a new
      generation of tryptase inhibitors.

PMID- 19852972
TI  - The evolution of phenotypic traits in a predator-prey system subject to Allee
      effect.
AB  - This paper considers the evolution of phenotypic traits in a community comprising
      the populations of predators and prey subject to Allee effect. The evolutionary
      model is constructed from a deterministic approximation of the stochastic process
      of mutation and selection. Firstly, we investigate the ecological and
      evolutionary conditions that allow for continuously stable strategy and
      evolutionary branching. We find that the strong Allee effect of prey facilitates
      the formation of continuously stable strategy in the case that prey population
      undergoes evolutionary branching if the Allee effect of prey is not strong
      enough. Secondly, we show that evolutionary suicide is impossible for prey
      population when the intraspecific competition of prey is symmetric about the
      origin. However, evolutionary suicide can occur deterministically on prey
      population if prey individuals undergo strong asymmetric competition and are
      subject to Allee effect. Thirdly, we show that the evolutionary model with
      symmetric interactions admits a stable limit cycle if the Allee effect of prey is
      weak. Evolutionary cycle is a likely outcome of the process, which depends on the
      strength of Allee effect and the mutation rates of predators and prey.

PMID- 19852973
TI  - Anti-social cells: predicting the influence of E-cadherin loss on the growth of
      epithelial cell populations.
AB  - The characteristics of biological tissues are determined by the interactions of
      large numbers of autonomous cells. These interactions can be mediated remotely by
      diffusive biochemical factors, or by direct cell-cell contact. E-cadherin is a
      protein expressed on the surface of normal epithelial cells that plays a key role
      in mediating intercellular adhesion via calcium-dependent homotypic interactions.
      E-cadherin is a metastasis-suppressor protein and its loss of function is
      associated with malignant progression. The purpose of this study was to apply an
      agent-based simulation paradigm in order to examine the emergent growth
      properties of mixed populations consisting of normal and E-cadherin defective
      cells in monolayer cell culture. Specifically, we have investigated the dynamics
      of normal cell:cell interactions in terms of intercellular adhesion and
      migration, and have used a simplified rule to represent the concepts of
      juxtacrine epidermal growth factor receptor (EGFR) activation and subsequent
      effect on cell proliferation. This cellular level control determines the overall
      population growth in a simulated experiment. Our approach provides a tool for
      modelling the development of defined biological abnormalities in epithelial and
      other biological tissues, raising novel predictions for future experimental
      testing. The results predict that even a relatively small number of abnormal
      ('anti-social') cells can modify the rate of the total population expansion, but
      the magnitude of this effect also depends on the extrinsic (culture) environment.
      In addition to directly influencing population dynamics, 'anti-social' cells can
      also disrupt the behaviour of the normal cells around them.

PMID- 19852974
TI  - First evidence of azaspiracids (AZAs): A family of lipophilic polyether marine
      toxins in scallops (Argopecten purpuratus) and mussels (Mytilus chilensis)
      collected in two regions of Chile.
AB  - Azaspiracids are a family of lipophilic polyether marine biotoxins that have
      caused a number of human intoxication incidents in Europe since 1995 following
      the consumption by consumers of intoxicated shellfish (Mytilus edulis). These
      azaspiracids have now been identified in mussels (Mytilus chilensis) and scallops
      (Argopecten purpuratus) from two Chilean locations. This is the first report of
      the occurrence of azaspiracid toxins in these species (Mytilus chilensis and
      Argopecten purpuratus) from Chile. The areas studied were Bahia Inglesa (III
      Region, 27 degrees SL) and Chiloe Archipelago, both important scallop and mussels
      farming areas. Separation of azaspiracid (AZA1), azaspiracid isomer (AZA6) and
      its analogues, 8-methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3), was
      achieved using reversed-phase LC and toxins were identified using a turbo
      electrospray ionisation (ESI) source, to a triple quadrupole mass spectrometer.
      In mussels, AZA1 was the predominant toxin in mussel hepatopancreas with AZA2,
      AZA3 and AZA6 present in approximate equivalent amounts in the remaining tissues,
      20-30% of the AZA1 level. AZA2 predominated in the scallop samples with the toxin
      almost entirely present in the hepatopancreas (digestive gland). AZA1 was only
      observed in some of the scallop samples and was present at 12-15% of the AZA2
      levels. Whilst the levels of AZAs in Chilean samples are below the EU regulatory
      limit of 160mug/kg, it is significant that this toxin is present in Pacific Ocean
      species. Consequently measures should be taken by regulatory authorities to
      implement regular seafood monitoring to ensure safety of harvested product.

PMID- 19852975
TI  - Distribution and linkage of domoic acid (amnesic shellfish poisoning toxins) in
      subcellular fractions of the digestive gland of the scallop Pecten maximus.
AB  - The king scallop Pecten maximus accumulates domoic acid, the main amnesic
      shellfish poisoning toxin, in the digestive gland for a long time. To try to find
      if the cause of this characteristic is the binding of the toxin to some cellular
      component, the subcellular distribution of domoic acid in the cells of the
      digestive gland was studied, by means of serial centrifugation, ultrafiltration
      and size exclusion chromatography (SEC). Domoic acid was found to be present
      mostly in soluble form in the cytosol, as more than 90% was found in the
      supernatant after a centrifugation of 1h at 45,000 x g, and passed a 10 kDa
      ultrafilter. The retention time of the peak with an absorption maximum of 242 nm-
      the one characteristic of domoic acid--observed in the SEC chromatograms of the
      scallop samples was found identical to be one of a reference solution of the
      toxin, indicating therefore, that domoic acid is free in the cytosol of the
      digestive gland of Pecten maximus. This finding turns the focus from binding to
      the lack of membrane transporters in this species of the scallop as the cause of
      the long retention time of domoic acid in this species.

PMID- 19852977
TI  - Venom analysis of long-term captive Pakistan cobra (Naja naja) populations.
AB  - Venom production facilities keep established colonies of captive snakes to obtain
      venom for research and antiserum production. Due to strict regulations of
      importation, some of these colonies are formed with only a small number of
      initial animals and consist of closely related individuals (sometimes siblings).
      To understand the effect of long-term captivity on the venom composition and its
      impact on antiserum production, we analyzed 15 long-term captive Naja naja
      (Pakistan) originating from two separate venom production colonies using liquid
      chromatography-mass spectrometry and electrophoresis. The chromatogram produced
      from each individual cobra venom was found to be different. When the protein
      molecular masses of the peaks were identified, it was found that all the venoms
      consisted of the same protein composition, but the concentration of the proteins
      were different. Although three-finger toxins and phospholipase A(2) enzymes are
      the major toxic components present in these venoms, there was a clear difference
      in the amounts of each individual isoform. Such variation may affect the ability
      of antivenoms in neutralizing the toxic components of the wild type venom.

PMID- 19852976
TI  - Lipid and cationic polymer based transduction of botulinum holotoxin, or toxin
      protease alone, extends the target cell range and improves the efficiency of
      intoxication.
AB  - Botulinum neurotoxin (BoNT) heavy chain (Hc) facilitates receptor-mediated
      endocytosis into neuronal cells and transport of the light chain (Lc) protease to
      the cytosol where neurotransmission is inhibited as a result of SNARE protein
      cleavage. Here we show that the role of BoNT Hc in cell intoxication can be
      replaced by commercial lipid-based and polycationic polymer DNA transfection
      reagents. BoNT "transduction" by these reagents permits efficient intoxication of
      neuronal cells as well as some non-neuronal cell lines normally refractory to
      BoNT. Surprisingly, the reagents facilitate delivery of recombinant BoNT Lc
      protease to the cytosol of both neuronal and non-neuronal cells in the absence of
      BoNT Hc, and with sensitivities approaching that of BoNT holotoxin. Transduction
      of BoNT, as with natural intoxication, is inhibited by bafilomycin A1,
      methylamine and ammonium chloride indicating that both pathways require endosome
      acidification. DNA transfection reagents facilitate intoxication by holotoxins,
      or isolated Lc proteases, of all three BoNT serotypes tested (A, B, E). These
      results suggest that lipid and cationic polymer transfection reagents facilitate
      cytosolic delivery of BoNT holotoxins and isolated Lc proteases by an endosomal
      uptake pathway.

PMID- 19852978
TI  - A case report of an unusual complication of Amanita phalloides poisoning:
      Development of cardiogenic shock and its successful treatment with intra-aortic
      balloon counterpulsation.
AB  - Amanita phalloides is responsible for the majority of the fatalities caused by
      mushroom poisoning. It causes damage in liver, kidneys and rarely pancreas,
      causing encephalopathic coma, disseminated intravascular coagulation, hemorrhage
      and hypovolemic shock. However, its effect on cardiac functions has not been
      established yet. In this case report, we aimed to present a female patient
      poisoned by A. phalloides mushroom complicated with multi-organ failure and
      cardiogenic shock due to advanced left ventricular systolic dysfunction. This
      case report was the first to show a successful treatment of cardiogenic shock due
      to mushroom poisoning with intra-aortic balloon counterpulsation, whereas she did
      not respond to other therapies.

PMID- 19852979
TI  - A unified model of illusory and occluded contour interpolation.
AB  - Models of contour interpolation have been proposed for illusory contour
      interpolation but seldom for interpolation of occluded contours. The identity
      hypothesis (Kellman & Loukides, 1987; Kellman & Shipley, 1991) posits that an
      early interpolation mechanism is shared by interpolated contours that are
      ultimately perceived as either illusory or occluded. Here we propose a model of
      such a unified interpolation mechanism for illusory and occluded contours,
      building on the framework established in Heitger, von der Heydt, Peterhans,
      Rosenthaler, and Kubler (1998). We show that a single, neurally plausible
      mechanism that is consistent with the identity hypothesis also generates contour
      interpolations in agreement with perception for cases of transparency, self
      splitting objects, interpolation with mixed boundary assignment, and "quasimodal"
      interpolations. Limiting cases for this local, feed-forward approach are
      presented, demonstrating that both early, local interpolation mechanisms and non
      local scene constraints are necessary for describing the perception of
      interpolated contours.

PMID- 19852980
TI  - Two recombinant peptides, SpStrongylocins 1 and 2, from Strongylocentrotus
      purpuratus, show antimicrobial activity against Gram-positive and Gram-negative
      bacteria.
AB  - The cysteine-rich strongylocins were the first antimicrobial peptides (AMPs)
      discovered from the sea urchin species, Strongylocentrotus droebachiensis.
      Homologous putative proteins (called SpStrongylocin) were found in the sister
      species, S. purpuratus. To demonstrate that they exhibit the same antibacterial
      activity as strongylocins, cDNAs encoding the 'mature' peptides (SpStrongylocins
      1 and 2) were cloned into a direct expression system fusing a protease cleavage
      site and two purification tags to the recombinant peptide. Both recombinant
      fusion peptides were expressed in a soluble form in an Escherichia coli strain
      tolerant to toxic proteins. Enterokinase was used to remove the fusion tags and
      purified recombinant SpStrongylocins 1 and 2 showed antimicrobial activity
      against both Gram-negative and Gram-positive bacteria. The results of membrane
      integrity assays against cytoplasmic membranes of E. coli suggest that both
      recombinant SpStrongylocins 1 and 2 conduct their antibacterial activity by
      intracellular killing mechanisms because no increase in membrane permeability was
      detected.

PMID- 19852981
TI  - Successful treatment of immune reconstitution inflammatory syndrome in Whipple's
      disease using thalidomide.
AB  - A patient with classic Whipple's disease developed erythema nodosum leprosum-like
      lesions and fever one month after the beginning of an accurate therapy with
      trimethoprim-sulfamethoxazole. Immune reconstitution inflammatory syndrome was
      suspected, but corticosteroid therapy failed to improve the patient. Finally,
      thalidomide was used and successfully induced rapid improvement.

PMID- 19852982
TI  - A semi-automated analysis method of small sensory nerve fibers in human skin
      biopsies.
AB  - Computerized detection method (CDM) software programs have been extensively
      developed in the field of astronomy to process and analyze images from nearby
      bright stars to tiny galaxies at the edge of the Universe. These object
      recognition algorithms have potentially broader applications, including the
      detection and quantification of cutaneous small sensory nerve fibers (SSNFs)
      found in the dermal and epidermal layers, and in the intervening basement
      membrane of a skin punch biopsy. Here, we report the use of astronomical software
      adapted as a semi-automated method to perform density measurements of SSNFs in
      skin-biopsies imaged by Laser Scanning Confocal Microscopy (LSCM). In the first
      half of the paper, we present a detailed description of how the CDM is applied to
      analyze the images of skin punch biopsies. We compare the CDM results to the
      visual classification results in the second half of the paper. Abbreviations used
      in the paper, description of each astronomical tools, and their basic settings
      and how-tos are described in the appendices. Comparison between the normalized
      CDM and the visual classification results on identical images demonstrates that
      the two density measurements are comparable. The CDM therefore can be used - at a
      relatively low cost - as a quick (a few hours for entire processing of a single
      biopsy with 8-10 scans) and reliable (high-repeatability with minimum user
      dependence) method to determine the densities of SSNFs.

PMID- 19852983
TI  - In search of a selective therapy of viral infections.
AB  - This article is meant as an introductory chapter to the special issue of
      Antiviral Research on "Twenty-five years of antiretroviral drug development:
      progress and prospects", commemorating the first description of azidothymidine
      (AZT) as an antiretroviral agent. This has prompted me to highlight some of the
      hallmarks that played an important role in my own search of a selective therapy
      of viral infections: i.e., the induction of interferon by double-stranded RNA
      [such as poly(I).poly(C)], allowing the cloning and expression of beta
      interferon; the discovery of the reverse transcriptase (RT) (and HIV as a
      retrovirus depending for its replication on RT), allowing the identification and
      development of a wide variety of RT inhibitors, nowadays used for the treatment
      of AIDS; the specificity of herpesvirus inhibitors such as acyclovir and BVDU, in
      the treatment of HSV and VZV infections; the role of acyclic nucleoside
      phosphonates (tenofovir, adefovir and cidofovir) in the treatment of HIV, HBV and
      DNA virus infections; and that of the NNRTIs (leading from TIBO to rilpivirine)
      as an essential part of the current anti-HIV drug cocktails. This article forms
      part of a special issue of Antiviral Research marking the 25th anniversary of
      antiretroviral drug discovery and development, vol. 85, issue 1, 2010.

PMID- 19852984
TI  - Prenatal exposure to moderate levels of ethanol alters social behavior in adult
      rats: relationship to structural plasticity and immediate early gene expression
      in frontal cortex.
AB  - The goals of the present study were to characterize the effects of prenatal
      exposure to moderate levels of ethanol on adult social behavior, and to evaluate
      fetal-ethanol-related effects on dendritic morphology, structural plasticity and
      activity-related immediate early gene (IEG) expression in the agranular insular
      (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol
      related alterations in social behavior were limited to reductions in social
      investigation in males. Repeated experience with novel cage-mates resulted in
      comparable increases in wrestling and social investigation among saccharin- and
      ethanol-exposed females, whereas social behavioral effects among males were more
      evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed
      profound increases in wrestling when social interaction was motivated by 24h of
      isolation. Baseline decreases in dendritic length and spine density in AID were
      observed in ethanol-exposed rats that were always housed with the same cage-mate.
      Modest experience-related decreases in dendritic length and spine density in AID
      were observed in saccharin-exposed rats housed with various cage-mates. In
      contrast, fetal-ethanol-exposed rats displayed experience-related increases in
      dendritic length in AID, and no experience-related changes in spine density. The
      only effect observed in Cg3 was a baseline increase in basilar dendritic length
      among male ethanol-exposed rats. Robust increases in activity-related IEG
      expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social
      interaction in saccharin-exposed rats, however, activity-related increases in IEG
      expression were not observed in fetal-ethanol-exposed rats in either region. The
      results indicate that deficits in social behavior are among the long-lasting
      behavioral consequences of moderate ethanol exposure during brain development,
      and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social
      behavior abnormalities.

PMID- 19852985
TI  - The role of local secondary structure in the function of the trans-splicing motif
      of Brugia malayi.
AB  - A 7-nt motif (the trans-splicing motif or TSM) was previously shown to be
      necessary and sufficient to direct trans-splicing of transgenic mRNAs in
      transgenic Brugia malayi embryos. Insertion of the TSM into two genes lacking a
      TSM homologue resulted in trans-splicing of transgenic mRNAs from one transgene
      but not the other, suggesting that local sequence context might affect TSM
      function. To test this hypothesis, constructs inserting the TSM into different
      positions of two B. malayi genes were tested for their ability to support trans
      splicing of transgenic mRNAs. Transgenic mRNAs derived from constructs in which
      the insertion of the TSM did not result in a perturbation of the local predicted
      secondary structure were trans-spliced, while those in which the TSM perturbed
      the local secondary structure were not. These data suggest that local secondary
      structure plays a role in the ability of the TSM to direct trans-splicing.

PMID- 19852986
TI  - Corticotropin-releasing hormone attenuates vascular endothelial growth factor
      release from human HaCaT keratinocytes.
AB  - OBJECTIVES: Corticotropin-releasing hormone (CRH) is a central component of the
      local hypothalamic-pituitary-adrenal (HPA) axis, which has a functional
      equivalent in the skin. To determine whether CRH and its receptor, CRH-R1,
      modulate the expression of vascular endothelial growth factor (VEGF), which is
      overexpressed in psoriatic epidermis and plays a causal role in the pathogenesis
      of psoriasis, we investigated the effect of CRH on the expression of VEGF in a
      human keratinocyte cell line (HaCaT) and whether this effect is via the mitogen
      activated protein kinase (MAPK) signal transduction pathways. METHODS: Real-time
      RT-PCR, ELISA assay and western blot were used in the present study to
      investigate the expression of VEGF in CRH-treated HaCaT cells. RESULTS: The mRNA
      and protein levels of VEGF in CRH-treated HaCaT cells were significantly
      attenuated. However, this downregulation was abrogated by pretreatment with
      antalarmin, SB203580 and SP600125; pretreatment with PD98059 did not attenuate
      the effects of CRH on the expression of VEGF. In addition, CRH treatment induced
      rapid phosphorylation of p38 MAPK and JNK1/2, and antalarmin, SB203580 and
      SP600125 inhibited CRH-induced phosphorylation of p38 MAPK and JNK1/2.
      CONCLUSIONS: CRH might downregulate the expression of VEGF through the CRH-R1 and
      MAPK (p38 MAPK and JNK1/2) signaling pathways in human HaCaT cells.

PMID- 19852987
TI  - Rethinking phosphatidylinositol 3-monophosphate.
AB  - A generally accepted view considers phosphatidylinositol 3-monophosphate
      (PtdIns3P) as a lipid confined to the endosomal compartment where it regulates
      trafficking pathways and is produced constitutively and exclusively by class III
      phosphoinositide 3-kinase (PI3K). Recent evidence suggests that this
      phosphoinositide has a more complex role as a second messenger involved in
      different physiological and pathological events and that specific intracellular
      localization of kinases and/or phosphatases is critical for PtdIns3P synthesis
      and PtdIns3P-dependent intracellular functions. Here, we review the current
      knowledge of the regulation and function of PtdIns3P and discuss how the view of
      PtdIns3P changed in the last few years.

PMID- 19852988
TI  - Phage-type specific markers identified by Diversity Arrays Technology (DArT)
      analysis of Salmonella enterica ssp. enterica serovars Enteritidis and
      Typhimurium.
AB  - Diversity Arrays Technology (DArT) was applied to differentiate between S.
      enterica serovar Enteritidis and Typhimurium strains, respectively. Ten and
      eleven, mainly phage and plasmid-related markers were identified for serovars
      Enteritidis and Typhimurium. In combination, these markers can be used for
      subtyping among and within phage types.

PMID- 19852989
TI  - The open reading frame 3 (ORF3) of porcine circovirus type 2 (PCV2) is
      dispensable for virus infection but evidence of reduced pathogenicity is limited
      in pigs infected by an ORF3-null PCV2 mutant.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine
      circovirus-associated diseases (PCVAD) in pigs. The open reading frame (ORF) 3 of
      PCV2 reportedly induces apoptosis and is associated with PCV2 pathogenicity. In
      this study, we first created an ORF3-null PCV2 mutant (muPCV2) by site-directed
      mutagenesis and demonstrated that the dimerized plasmid DNA of muPCV2 clone is
      infectious when injected intramuscularly (I.M.) into pigs. Subsequently, by using
      a well-characterized pig model we compared the pathogenicity of the muPCV2 and
      the wildtype PCV2. Thirty-one pigs were divided into 3 groups of 11, 10, and 10
      each: group 1 pigs were each inoculated I.M. with PBS buffer as negative
      controls, group 2 pigs each with 200 microg of muPCV2 infectious DNA clone, and
      group 3 pigs each with 200 microg of wildtype PCV2 infectious DNA clone. Blood
      was collected prior to inoculation and weekly thereafter, and tested for PCV2
      antibodies by ELISA and serum viral DNA loads by quantitative PCR. All pigs were
      necropsied at 35 days post-inoculation. The results showed that pigs inoculated
      with muPCV2 had a delayed seroconversion and lower serum viral load. However,
      there was no significant difference in the average scores of the histological or
      gross lesions or the amount of PCV2-specific antigen in tissues between wildtype
      PCV2- and muPCV2-inoculated groups. Thus, the data from this study do not fully
      support the conclusion of a previous report regarding PCV2 attenuation by
      abrogation of ORF3 although the results did show that ORF3 is dispensable for
      PCV2 replication in pigs.

PMID- 19852990
TI  - Structure-activity relationship of human liver-expressed antimicrobial peptide 2.
AB  - Liver-expressed antimicrobial peptide 2 (LEAP-2) is a 40-residue cationic peptide
      originally purified from human blood ultrafiltrate. The native peptide contains
      two disulfide bonds and is unique regarding its primary structure. Its biological
      role is not known but a previous study showed that chemically synthesized LEAP-2
      exhibited in vitro antimicrobial activities against several Gram-positive
      bacteria. In order to determine its antimicrobial mode of action, we expressed
      human recombinant LEAP-2 in Escherichia coli. Circular dichroism spectroscopy and
      nuclear magnetic resonance analyses showed that the structure of the recombinant
      peptide was identical to that of the chemically synthesized and oxidized LEAP-2,
      with two disulfide bonds between Cys residues in relative 1-3 and 2-4 positions.
      Minimal inhibitory concentration (MIC) of the recombinant human LEAP-2 was
      determined by a conventional broth dilution assay. It was found to be
      bactericidal against Bacillus megaterium at a 200microM concentration.
      Interestingly, the linear LEAP-2 had a greater antimicrobial activity with a MIC
      value of 12.5microM, which was comparable to that of magainin2. SYTOX Green
      uptake was used to assess bacterial membrane integrity. Linear LEAP-2 and
      magainin2 permeabilized B. megaterium membranes with the same efficiency, whereas
      oxidized LEAP-2 did not induce stain uptake. Binding of the peptides to plasmid
      DNA was evaluated by gel retardation assays. The DNA-binding efficacy of linear
      LEAP-2 was three times higher than that of the peptide-containing disulfide
      bridges. Altogether, these results show that the secondary structure of human
      LEAP-2 has a profound impact on its antibacterial activity.

PMID- 19852991
TI  - Combining in silico transcriptome mining and biological mass spectrometry for
      neuropeptide discovery in the Pacific white shrimp Litopenaeus vannamei.
AB  - The shrimp Litopenaeus vannamei is arguably the most important aquacultured
      crustacean, being the subject of a multi-billion dollar industry worldwide. To
      extend our knowledge of peptidergic control in this species, we conducted an
      investigation combining transcriptomics and mass spectrometry to identify its
      neuropeptides. Specifically, in silico searches of the L. vannamei EST database
      were conducted to identify putative prepro-hormone-encoding transcripts, with the
      mature peptides contained within the deduced precursors predicted via online
      software programs and homology to known isoforms. MALDI-FT mass spectrometry was
      used to screen tissue fragments and extracts via accurate mass measurements for
      the predicted peptides, as well as for known ones from other species. ESI-Q-TOF
      tandem mass spectrometry was used to de novo sequence peptides from tissue
      extracts. In total 120 peptides were characterized using this combined approach,
      including 5 identified both by transcriptomics and by mass spectrometry (e.g.
      pQTFQYSRGWTNamide, Arg(7)-corazonin, and pQDLDHVFLRFamide, a myosuppressin), 49
      predicted via transcriptomics only (e.g. pQIRYHQCYFNPISCF and pQIRYHQCYFIPVSCF,
      two C-type allatostatins, and RYLPT, authentic proctolin), and 66 identified
      solely by mass spectrometry (e.g. the orcokinin NFDEIDRAGMGFA). While some of the
      characterized peptides were known L. vannamei isoforms (e.g. the pyrokinins
      DFAFSPRLamide and ADFAFNPRLamide), most were novel, either for this species (e.g.
      pEGFYSQRYamide, an RYamide) or in general (e.g. the tachykinin-related peptides
      APAGFLGMRamide, APSGFNGMRamide and APSGFLDMRamide). Collectively, our data not
      only expand greatly the number of known L. vannamei neuropeptides, but also
      provide a foundation for future investigations of the physiological roles played
      by them in this commercially important species.

PMID- 19852993
TI  - Blockade of adenosine A2A receptors downregulates DARPP-32 but increases ERK1/2
      activity in striatum of dopamine deficient "weaver" mouse.
AB  - In the present study we investigated the signal transduction cascade modulated by
      adenosine A(2A) receptors under chronic dopamine deficiency in the "weaver"
      mouse. We determined the phosphorylation state of cAMP-regulated phosphoprotein
      of 32 kDa (DARPP-32) at Thr34 and of Extracellular Signal-regulated Protein
      Kinases 1/2 (ERK1/2), under basal conditions and after in vivo stimulation of
      A(2A) receptors by administration of the agonist CGS21680. Our results revealed
      that the endogenous levels of phospho-DARPPP-32 and phospho-ERK1/2 are elevated
      in "weaver" striatum probably as an adaptation phenomenon to gradual dopaminergic
      neurodegeneration appearing in this animal model, characterized as phenocopy of
      Parkinson's disease. Stimulation of A(2A) receptors by CGS21680 further increases
      phospho-DARPP-32 but downregulates significantly the elevated phospho-ERK1/2
      levels bringing them close to those observed in wild type animals. Consistently,
      blockade of A(2A) receptors by MSX-3 (A(2A) receptor antagonist) downregulates
      phospho-DARPP-32 but significantly increases even more the
      phosphorylation/activation of ERK1/2. These results indicate that under chronic
      dopamine deficiency (a) the A(2A)/cAMP/PKA/DARPP-32 cascade is overactive due to
      the elevated endogenous phospho-DARPP-32 levels and (b) the A(2A) receptor
      modulatory effect on ERK1/2 signaling is dysregulated exerting opposing action
      compared to that observed in normal animals (Quiroz et al., 2006), i.e. in
      "weaver" animals A(2A) receptor blockade increases the activity of ERK1/2
      cascade. This could be of clinical relevance since A(2A) antagonists are already
      used in clinical trials for ameliorating Parkinson's disease (PD) symptoms.

PMID- 19852992
TI  - Promethazine protects against 3-nitropropionic acid-induced neurotoxicity.
AB  - Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a
      potentially neuroprotective compound in a NINDS screening program. It was shown
      to protect against ischemia in mice, to delay disease onset in a mouse model of
      amyotrophic lateral sclerosis and to inhibit Ca(2+)-induced mitochondrial
      permeability transition in rat liver mitochondria. We investigated whether PMZ
      could protect against the neurotoxic effects induced by 3-nitropropionic acid (3
      NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's
      disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP
      were treated with PMZ. The findings indicate that chronic PMZ treatment
      significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic
      neurons and number of apoptotic cells in the striatum. PMZ showed a strong
      neuroprotective effect against 3-NP toxicity in vivo.

PMID- 19852995
TI  - Dissociation of performance parameters at the IAT requires specific exercise
      recommendations for depressed patients.
AB  - Aerobic exercise training is considered an adequate complementary treatment
      strategy for major depressive disorder (MDD). However, there is a need for
      comparative methodological investigations to determine the appropriate exercise
      intensity for these patients. The study compared submaximal exercise intensity
      determination with those derived from maximal parameters such as percentages of
      heart rate reserve (HRR), maximal heart rate (HR(max)) and peak oxygen uptake
      (VO(2peak)) of patients and controls. An exhaustive incremental bicycle exercise
      test was completed by 15 female MDD patients and matched controls. The individual
      anaerobic lactate threshold (IAT) as a gold standard to determine individual
      aerobic exercise intensity was assessed according to Stegmann and coworkers.
      Exercise intensities at 70 and 85% of HR(max), 70 and 85% of HRR and 50 to 80% of
      VO(2peak) were compared to the IAT. Patients suffering from MDD switched earlier
      to anaerobic metabolism than matched healthy controls. But interestingly, the
      level of self-rated perceived exertion, concentration of lactate, respiratory
      exchange ratio and heart rate at the IAT level revealed no significant difference
      between both groups. Due to a growing number of clinical aerobic exercise
      treatments in depressive disorders exercise intensities >70% of (a) HR(max), (b)
      HRR, (c) VO(2peak) should be amended by the IAT and Borg scale measurements to
      avoid over challenging as well as increased anaerobic metabolism.

PMID- 19852996
TI  - Total and regional brain volume reductions due to the Syndrome of Irreversible
      Lithium-Effectuated Neurotoxicity (SILENT): a voxel-based morphometric study.

PMID- 19852997
TI  - Modulatory role of alizarin from Rubia cordifolia L. against genotoxicity of
      mutagens.
AB  - Rubia cordifolia L. (Rubiaceae) is an important medicinal plant used in the
      Ayurvedic medicinal system. Its use as a traditional therapeutic has been related
      to the treatment of skin disorders and cancer. Besides its medicinal value,
      anthraquinones from this plant are used as natural food colourants and as natural
      hair dyes. Dyes derived from natural sources have emerged as important
      alternatives to synthetic dyes. Alizarin (1,2-dihydroxyanthraquinone) was
      isolated and characterized from R. cordifolia L. and evaluated for its
      antigenotoxic potential against a battery of mutagens viz. 4-nitro-o
      phenylenediamine (NPD) and 2-aminofluorene (2-AF) in Ames assay using TA98 tester
      strain of Salmonella typhimurium; hydrogen peroxide (H(2)O(2)) and 4
      nitroquinoline-1-oxide (4NQO) in SOS chromotest using PQ37 strain of Escherichia
      coli and in Comet assay using human blood lymphocytes. Our results showed that
      alizarin possessed significant modulatory role against the genotoxicity of
      mutagens.

PMID- 19852999
TI  - Cytotoxic and apoptotic activity of essential oil from Ocimumviride towards COLO
      205 cells.
AB  - We investigated the apoptosis inducing effect of essential oil (EO) from aerial
      parts of Ocimumviride in human colorectal adenocarcinoma cells (COLO 205 cell
      line). The COLO 205 cells were exposed to 0.0125-0.1 microl/ml of EO for 24, 48
      and 72h. Growth inhibition was determined by sulphorhodamine B (SRB) assay.
      Double staining with acridine orange and ethidium bromide for nuclear changes was
      performed. Cell cycle analysis and change in mitochondrial membrane potential was
      quantified by flow cytometry. Subsequently, using annexin V/PI assay, the
      proportion of cells actively undergoing apoptosis was determined. Changes in DNA
      were observed by DNA ladder assay. Eventually the surface morphology of apoptotic
      cells was studied by scanning electron microscopy. EO is cytotoxic to COLO 205
      cells in dose and time-dependent manner, as is evident by SRB assay. This
      observed cell death was due to apoptosis, as established by annexin V/PI assay,
      DNA ladder formation and scanning electron microscopy. Our results reveal that EO
      has apoptosis inducing effect against COLO 205 cells in vitro and is a promising
      candidate for further anti-cancer study.

PMID- 19852998
TI  - Protective effect of Corchorus olitorius leaves on sodium arsenite-induced
      toxicity in experimental rats.
AB  - The present study was undertaken to evaluate the protective effect of aqueous
      extract of Corchorus olitorius leaves (AECO) against sodium arsenite-induced
      toxicity in experimental rats. The animals exposed to sodium arsenite at a dose
      of 10mg/kg body weight p.o. for 10days exhibited a significant inhibition
      (p<0.01) of hepatic and renal antioxidant enzymes namely superoxide dismutase,
      catalase, glutathione-S-transferase, glutathione peroxidase and glutathione
      reductase. In addition, arsenic intoxication significantly decreased (p<0.01) the
      level of reduced glutathione and increased (p<0.01) the levels of oxidized
      glutathione and thiobarbituric acid reactive substances in selected tissues.
      Treatment with AECO at doses of 50 and 100mg/kg body weight p.o. for 15days prior
      to arsenic intoxication significantly improved hepatic and renal antioxidant
      markers in a dose dependant manner. AECO treatment also significantly reduced the
      arsenic-induced DNA fragmentation of hepatic and renal tissues. Histological
      studies on the ultrastructural changes of liver and kidney supported the
      protective activity of the AECO. The results concluded that the treatment with
      AECO prior to arsenic intoxication has significant role in protecting animals
      from arsenic-induced hepatic and renal toxicity.

PMID- 19853000
TI  - The pyrethroid metabolites 3-phenoxybenzoic acid and 3-phenoxybenzyl alcohol do
      not exhibit estrogenic activity in the MCF-7 human breast carcinoma cell line or
      Sprague-Dawley rats.
AB  - Synthetic pyrethroids are one of the most frequently and widely used class of
      insecticides, primarily because they have a higher insect to mammalian toxicity
      ratio than organochlorines or organophosphates. The basic structure of
      pyrethroids can be characterized as an acid joined to an alcohol by an ester
      bond. Pyrethroid degradation occurs through either oxidation at one or more sites
      located in the alcohol or acid moieties or hydrolysis at the central ester bond,
      the latter reaction being important for mammalian metabolism of most pyrethroids.
      The primary alcohol liberated from the ester cleavage is hydroxylated to 3
      phenoxybenzyl alcohol, which for most pyrethroids is then oxidized to 3
      phenoxybenzoic acid. These products may then be conjugated with amino acids,
      sulfates, sugars, or sugar acids. In vitro studies have suggested that some of
      the pyrethroids may have estrogenic activity. Interestingly, the chemical
      structure of specific pyrethroid metabolites indicates that they may be more
      likely to interact with the estrogen receptor than the parent compounds. Two of
      the pyrethroid metabolites, 3-phenoxybenzoic acid (3PBA) and 3-phenoxybenzyl
      alcohol (3PBalc) have been reported to have endocrine activity using a yeast
      based assay. 3PBAlc exhibited estrogenic activity with reported EC(50)s of 6.67 x
      10(-6) and 2 x 10(-5) while 3PBAcid exhibited anti-estrogenic activity with a
      calculated IC(50) of 6.5 x 10(-5). To determine if the metabolites were able to
      cause the same effects in a mammalian system, the estrogen-dependent cell line,
      MCF-7, was utilized. Cells were treated with 1.0, 10.0 or 100.0 microM
      concentrations of each metabolite and cytotoxicity was assessed. The two lowest
      concentrations of both metabolites did not induce cell death and even appeared to
      increase proliferation over that of the control cells. However, when cellular
      proliferation was measured using a Coulter counter neither metabolite stimulated
      proliferation (1.0 nM, 10.0 nM, or 10.0 microM) or induced an estrogen receptor
      alpha/ERE-controlled luciferase reporter in the MCF-7 cells. Following the in
      vitro screenings, the metabolites were then evaluated for estrogenic activity in
      vivo using the uterotrophic assay in Sprague-Dawley rats. Animals were orally
      gavaged (10.0, 5.0, and 1.0 mg/kg) once daily for 3 days. Neither metabolite had
      any effect on uterine wet weight, body weight, or organ weight. Lastly, in order
      to determine if either metabolite was able to alter the onset of puberty,
      immature female rats were orally gavaged (10.0, 5.0, and 1.0 mg/kg) once a day
      with the metabolites beginning 1 day post-weaning until the onset of puberty as
      evidenced by vaginal opening (VO). Again, neither metabolite had any effect on
      the onset of VO.

PMID- 19853001
TI  - Up-regulation of CYP1A1 by rutaecarpine is dependent on aryl hydrocarbon receptor
      and calcium.
AB  - Rutaecarpine is a quinazolinocarboline alkaloid isolated from a traditional
      Chinese medicinal fruit, Evodia rutaecarpa. In the present study, we investigated
      the effect of rutaecarpine on CYP1A1 expression mediated by [Ca(2+)] and the AhR
      pathway in mouse hepatoma Hepa-1c1c7 cells. Rutaecarpine also significantly
      increased CYP1A1 enzyme activity and mRNA and protein levels. Rutaecarpine
      markedly induced XRE and AhR binding activity. CH-223191, an AhR antagonist,
      blocked the rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein
      expression. In addition, rutaecarpine remarkably induced the phosphorylation of
      Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK). W7 and BAPTA/AM, a CaM
      antagonist and an intracellular Ca(2+) chelator, respectively, blocked the
      rutaecarpine-induced CYP1A1 enzyme activity and mRNA and protein expression.
      These results indicate that rutaecarpine induces CYP1A1 expression through AhR-
      and calcium-dependent mechanisms.

PMID- 19853002
TI  - Differential aggressiveness of ethylenediamine tetraacetic acid in causing canal
      wall erosion in the presence of sodium hypochlorite.
AB  - OBJECTIVE: This study tested the hypothesis that the use of ethylenediamine
      tetraacetic acid (EDTA) as a final irrigant causes canal wall erosion only after
      prolonged use of 5.25% sodium hypochlorite (NaOCl) as the initial irrigant.
      METHODS: Two irrigation protocols were employed: (1) 5.25% NaOCl as the initial
      irrigant for 10 min and 17% EDTA as the final irrigant for 2 min; and (2) 5.25%
      NaOCl for 60 min and 17% EDTA for 2 min. Flexural strengths of dentine beams
      prepared from human mid-coronal dentine were evaluated using a miniature three
      point bending device after they were irrigated with either protocol. Transmission
      electron microscopy was used to examine the conditions of instrumented canal
      walls irrigated with either protocol after they were bonded with methacrylate
      resin-based sealers. RESULTS: Immersion of dentine beams in NaOCl for 60 min
      instead of 10 min prior to the use of EDTA resulted in a significant (p<0.001)
      decline in flexural strength. For both NaOCl initial rinsing times, a 2-min final
      irrigation with EDTA created similar 0.5 microm thick demineralisation fronts.
      However, extensive surface and subsurface erosion of radicular dentine was seen
      only when the dentine was immersed in NaOCl for 60 min. CONCLUSION: The apparent
      aggressiveness of EDTA in causing canal wall erosion is attributed to the
      prolonged use of NaOCl. The associated decline in dentine flexural strength has
      potential clinical relevance when thin pulp chamber dentine is immersed in NaOCl
      for lengthy periods during canal instrumentation. This may render root-treated
      teeth more prone to vertical fracture.

PMID- 19853003
TI  - The C-terminal amphipathic alpha-helix of Pseudomonas aeruginosa PelC outer
      membrane protein is required for its function.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen, which causes numerous
      infections and can adopt a versatile lifestyle. During chronic infection, P.
      aeruginosa becomes established as a bacterial community known as a biofilm.
      Biofilm formation results from the production of a matrix mainly comprised of
      exopolysaccharides. P. aeruginosa possesses several gene clusters which
      contribute to the formation of the matrix, including the pel genes. Among the pel
      genes, pelC encodes an outer membrane protein, which may serve as a transporter
      of polysaccharide to the bacterial cell surface. Whereas outer membrane proteins
      usually display an amphipathic beta-barrel fold, we show that PelC requires a C
      terminal amphipathic alpha-helix for outer membrane insertion and function. Such
      a structural feature has only previously been reported for the Wza outer membrane
      protein of Escherichia coli, and our data suggest that this characteristic may be
      found in a large family of proteins, particularly outer membrane proteins
      specialized in polysaccharide transport.

PMID- 19853004
TI  - Alterations of matrix metalloproteinases, gastric mucin and prostaglandin E(2)
      levels by pectic polysaccharide of swallow root (Decalepis hamiltonii) during
      ulcer healing.
AB  - Gastric ulcer is a multi-step disease caused due to imbalance between mucosal
      defense and aggressive factors. Available anti-ulcer drugs although effective at
      various steps of ulcer pathogenecity, pose adverse effects. Pectic polysaccharide
      (SRPP) from swallow root (Decalepis hamiltonii) - previously shown to possess
      ulcer preventive effect against swim stress and ethanol induced gastric ulcers.
      In the current study, alteration of matrix metalloproteinases, gastric mucin and
      prostaglandin E(2) levels during polysaccharide mediated ulcer healing was
      determined in acetic acid induced gastric ulcer model in Wistar albino rats.
      Results indicated the potential ulcer healing effect of SRPP as evidenced by
      approximately 90% reduction in ulcer index; improvement in the antioxidant
      defense such as increase of glutathione levels together with significant
      reduction in lipid and protein oxidation and protection to damaged gastric mucin.
      Further, histological studies substantiated the result of the recovery of mucin
      that was eroded during ulceration, rejuvenation of mucosal epithelium and
      enhancement of high molecular mass mucin as opposed to the degraded approximately
      55 kDa mucin that appeared only during ulcer condition. Matrix metalloproteinases
      (MMPs) that are involved in tissue injury was found to be modulated by SRPP
      treatment in addition to increased cytoprotectivity due to enhanced synthesis of
      PGE(2) that necessitates the active proliferation of gastric mucin cells.
      Further, reduction in approximately 3 folds of galectin-3, an inflammatory marker
      suggests gastro protection against acid induced inflammation and gastric wall
      damages. Overall, studies show the effectiveness of SRPP in inhibiting MMPs and
      galectin-3 levels which were up-regulated during ulcer conditions. In addition
      SRPP ensured cytoprotectivity and rejuvenation of mucosal barrier via PGE(2)
      trigger leading to ulcer healing.

PMID- 19853005
TI  - Studies on the hippocampal formation: From basic development to clinical
      applications: Studies on schizophrenia.
AB  - The hippocampal formation plays a critical role in cognitive function. The
      developmental events that shape the hippocampal formation are continuing to be
      elucidated and their implications for brain function are emerging as well as
      applying those advances to interventions that have important possibilities for
      the treatment of brain dysfunction. The story told in this chapter is about the
      use of the in oculo transplant method to illuminate intrinsic and extrinsic
      features that underlie the development of the dentate gyrus and adjacent
      hippocampus and the role of one molecule in the hippocampus and schizophrenia.
      Schizophrenia, originally conceptualized as a dysfunction in dopaminergic
      neurotransmission, is now known to involve multiple neuronal systems. Dysfunction
      of hippocampal neurons is emerging as one of its signature pathological features.
      Basic insights into the development and function of hippocampal interneurons form
      the basis of a new treatment initiative for this illness. Evidence for the role
      of the alpha 7-nicotinic acetylcholine receptor in the development and function
      of these neurons in rodents has led to human trials of nicotinic agonists for
      cognitive dysfunction in schizophrenia and the possibility of improving
      hippocampal development in children at risk for schizophrenia by perinatal
      supplementation with choline, which can act as an alpha 7-nicotinic acetylcholine
      receptor agonist.

PMID- 19853006
TI  - Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and
      anxiety: Structural and functional analysis.
AB  - Dopamine plays an important role in fear and anxiety modulating a cortical brake
      that the medial prefrontal cortex exerts on the anxiogenic output of the amygdala
      and have an important influence on the trafficking of impulses between the
      basolateral (BLA) and central nuclei (CeA) of amygdala. Dopamine afferents from
      the ventral tegmental area innervate preferentially the rostrolateral main and
      paracapsular intercalated islands as well as the lateral central nucleus of
      amygdala activating non-overlapping populations of D1- and D2-dopamine receptors
      located in these structures. Behaviorally, the intra-amygdaloid infusion of D1
      agonists and antagonists elicits anxiogenic and anxiolytic effects respectively
      on conditioned and non-conditioned models of fear/anxiety suggesting an
      anxiogenic role for D1 receptors in amygdala. The analysis of the effects of D2
      agonists and antagonists suggest that depending of the nature of the threat the
      animal experiences in anxiety models either anxiogenic or anxiolytic effects are
      elicited. It is suggested that D1- and D2-dopamine receptors in the amygdala may
      have a differential role in the modulation of anxiety. The possibility is
      discussed that D1 receptors participate in danger recognition facilitating
      conditioned-unconditioned associations by the retrieval of the affective
      properties of the unconditioned stimuli, and in the control of impulse
      trafficking from cortical and BLA regions to BLA and CeA nuclei respectively
      whereas D2 receptors have a role in setting up adaptive responses to cope with
      aversive environmental stimuli.

PMID- 19853007
TI  - The discovery of central monoamine neurons gave volume transmission to the wired
      brain.
AB  - The dawn of chemical neuroanatomy in the CNS came with the discovery and mapping
      of the central dopamine, noradrenaline and 5-hydroxytryptamine neurons by means
      of transmitter histochemistry using the Falck-Hillarp formaldehyde fluorescence
      technique in the early 1960s. Our mapping of the central monoamine neurons was
      continued and further established with tyrosine hydroxylase, dopa decarboxylase
      and dopamine-beta-hydroxylase immunohistochemistry in collaboration with Menek
      Goldstein and Tomas Hokfelt. During recent years an evolutionary constraint in
      the nuclear parcellation of the DA, NA and 5-HT neurons was demonstrated in the
      order Rodentia and other mammals. The abundant existence of global monoamine
      varicose nerve terminal networks synthesizing, storing and releasing monoamines
      in various parts of the CNS, including the release of DA by tubero-infundibular
      DA neurons as a prolactin inhibitory factor from the external layer of the median
      eminence into the portal vessels and the appearance of extraneuronal DA
      fluorescence after, e.g., treatment with amphetamine in nialamide pretreated rats
      (Falck-Hillarp technique) were also remarkable observations. These observations
      and others like the discovery of transmitter-receptor mismatches opened up the
      possibility that monoamines were modulating the wired brain, built up mainly by
      glutamate and GABA neurons, through diffusion and flow in the extracellular fluid
      of the extracellular space and in the CSF. This transmission also involved long
      distance channels along myelinated fibers and blood vessels and was called volume
      transmission (VT). The extracellular space (ECS), filled with a 3D matrix, plays
      a fundamental role in this communication. Energy gradients for signal migration
      in the ECS are produced via concentration, temperature and pressure gradients,
      the latter two allowing a flow of the ECF and CSF carrying the VT signals. The
      differential properties of the wiring transmission (WT) and VT circuits and
      communication channels will be discussed as well as the role of neurosteroids and
      oxytocin receptors in volume transmission leading to a new understanding of the
      integrative actions of neuronal-glial networks. The role of tunneling nanotubes
      with mitochondrial transfer in CNS inter alia as part of neuron-glia interactions
      will also be introduced representing a novel type of wiring transmission. The
      impact of the technicolour approach to the connectome for the future
      characterization of the wired networks of the brain is emphasized.

PMID- 19853008
TI  - Looking at neurotransmitters in the microscope.
AB  - This review article covers the early period of my career. I first summarize
      research initiated by the late Nils-Ake Hillarp, after his appointment in 1962 as
      professor in the Department of Histology at Karolinska Institutet. He only lived
      for three more years, but during this short period he started up a group of ten
      students who explored various aspects of the three monoamine transmitters,
      dopamine, noradrenaline and 5-hydroxytryptamine, using the new formaldehyde
      fluorescence method developed by Bengt Falck and Hillarp in Lund. This method
      allowed visualization of the cellular localization in the microscope of these
      monoamines, which introduced a new discipline in neurobiology-chemical
      neuroanatomy. I then deal with work aiming at localizing the monoamines at the
      ultrastructural level, as well as attempts to use radioactively labeled
      aminoacids, especially gamma-aminobutyric acid (GABA), and autoradiography, to
      identify, in the microscope, neurons using such transmitters. Finally, our
      immunohistochemical work together with Kjell Fuxe and the late Menek Goldstein,
      using antibodies to four monoamine-synthesizing enzymes is summarized, including
      some aspects on the adrenaline neurons, which had escaped detection with the
      Falck-Hillarp technique.

PMID- 19853009
TI  - Grafted dopamine neurons: Morphology, neurochemistry, and electrophysiology.
AB  - Grafting of dopamine-rich tissue to counteract the symptoms in Parkinson's
      disease became a promising tool for future treatment. This article discusses how
      to improve the functional outcome with respect to graft outgrowth and functions
      of dopamine release and electrophysiological responses to graft implantation in
      the host brain striatal target. It has been documented that a subpopulation of
      the dopamine neurons innervates the host brain in a target-specific manner, while
      some of the grafted dopamine neurons never project to the host striatum.
      Neurochemical studies have demonstrated that the graft-induced outgrowth
      synthesize, store, metabolize and release dopamine and possibly other
      neurotransmitters such as 5-HT. Furthermore, the released dopamine affects the
      dopamine-depleted brain in areas that are larger than the graft-derived nerve
      fibers reach. While stem cells will most likely be the future source of cells to
      be used in grafting, it is important to find the guiding cues for how to
      reinnervate the dopamine-depleted striatum in a proper way with respect to the
      dopamine subpopulations of A9 and A10 to efficiently treat the motor
      abnormalities seen in Parkinson's disease.

PMID- 19853010
TI  - Connection between inflammatory processes and transmittor function-Modulatory
      effects of interleukin-1.
AB  - Cells in the nervous system can respond to different kinds of stress, e.g.
      injury, with production and release of inflammatory molecules, including
      cytokines. One of the most important proinflammatory cytokines is interleukin-1,
      affecting most organs of the body. The high constitutive expression of
      interleukin-1 in the adrenal gland provides a source for local and systemic
      actions, in addition to activated monocytes. In the brain, the constitutive
      expression is low, but activated microglia produce and release interleukin-1
      during pathological conditions such as neurodegenerative disorders (e.g. stroke,
      traumatic brain injury, Alzheimer's disease, Parkinson's disease). Interleukin-1
      has an important role in mediating 'sickness symptoms' such as fever, in response
      to infections. Its role in neurodegeneration is not fully elucidated, but there
      is evidence for involvement in both amyloidosis and tau pathology, major
      neuropathological hallmarks of Alzheimer's disease. The interleukin-1 family at
      present consists of 11 members, one of which is the endogenous receptor
      antagonist. Overexpression of this antagonist in the CNS in a transgenic mouse
      strain, Tg hsIL-1ra, has allowed studies on morphological and functional effects
      of blocking interleukin-1 receptor-mediated activity in the brain. Marked
      alterations of brain morphology such as reduced hippocampal and cortical volume
      correlate with behavioural deficits. Decreased anxiety and impaired long-term
      memory are among the consequences. Intact interleukin-1 signalling is important
      for the brain's ability to adapt to acute and chronic neuroinflammation.
      Increased amplitude and prolongation of proinflammatory cytokine production
      underly the behavioural alterations characteristic for ageing. Moreover,
      deregulated expression of interleukin-1 is associated with ageing-related chronic
      neurodegenerative disorders.

PMID- 19853011
TI  - Nitric oxide neurons and neurotransmission.
AB  - Nitric oxide was identified as a biological intercellular messenger just over 20
      years ago, and its presence and potential importance in the nervous system was
      immediately noted. With the cloning of NO synthase and the physiological NO
      receptor soluble guanylyl cyclase, a variety of histochemical methods quickly led
      to a rather complete picture of where NO is produced and acts in the nervous
      system. However, the details regarding the subcellular localization of NO
      synthase and the identity of its molecular binding partners require further
      clarification. Although the hypothesis that calcium influx via activation of NMDA
      receptors is a key trigger for NO production has proven very popular and led to
      suggested roles for NO in synaptic plasticity, there is little direct evidence to
      support this notion. Instead, studies from the peripheral nervous system indicate
      a key role for voltage-sensitive calcium channels in regulating NO synthase
      activity. A similar mechanism may also be important in central neurons, and it
      remains an important task to identify the precise sources of calcium regulating
      NO production in specific NO neurons. Also, although cGMP production appears to
      mediate the physiological signaling by NO, the specific roles of cGMP-dependent
      ion channels, protein kinases and phosphodiesterases in mediating NO action
      remain to be determined.

PMID- 19853013
TI  - The catecholamine neuron: Historical and future perspectives.
AB  - My goals for this perspective are to enumerate what I consider to have been the
      major discoveries in the investigations of the central catecholamine neuron
      systems from the synaptic, cellular and systems physiological and
      neurohistochemical perspectives. To do so, I will emphasize here the synaptic and
      physiological aspects of the central noradrenergic (NE) system, considering both
      the past research and what we may expect to witness in the decades ahead.

PMID- 19853014
TI  - Mouse MAPC-mediated immunomodulation: Cell-line dependent variation.

PMID- 19853012
TI  - A dual-hit animal model for age-related parkinsonism.
AB  - Parkinson's disease is a neurological disorder which afflicts an increasing
      number of individuals. If the wider complex of extrapyramidal symptoms referred
      to as "age-related parkinsonism" is included, the incidence is near 50% of the
      population above 80 years of age. This review summarizes recent studies from our
      laboratories as well as other research groups in the quest to explore the multi
      faceted etiology of age-related neurodegeneration, in general, and degeneration
      of the substantia nigra dopaminergic neurons, in particular. Our work during
      recent years has focused on assessment of potential interactive effects of a
      reduction in glial cell line-derived neurotrophic factor (GDNF) and the aging
      process (intrinsic factors) and early neurotoxin exposure (an extrinsic factor)
      on dopamine (DA) systems and the behaviors they mediate. The guiding hypothesis
      directing the research to be described was that a combination of the two factors
      would exacerbate the decline in the DA transmitter system function that occurs
      during aging. The results obtained were consistent with the well-established
      aging-related decline in function and structure of neurons utilizing DA as a
      transmitter and motor function, and extended knowledge by establishing that the
      genetic reduction of Gdnf exacerbated these aging related changes. Thus, GDNF
      reduction appears to increase the vulnerability of the DA neurons to the many
      different challenges associated with the aging process. Assessment of
      methamphetamine effects on young Gdnf(+/-) mice indicated that reduced GDNF
      availability increased the vulnerability of DA systems to this well-established
      neurotoxin. The work discussed in this review is consistent with earlier work
      demonstrating the importance of GDNF for maintenance of DA neurons and also
      provides a novel model for progressive DA degeneration and motor dysfunction.

PMID- 19853016
TI  - A multi-objective differential evolutionary approach toward more stable gene
      regulatory networks.
AB  - Models are of central importance in many scientific contexts. Mathematical and
      computational modeling of genetic regulatory networks promises to uncover the
      fundamental principles of living systems. Biological models, such as gene
      regulatory models, can help us better understand interactions among genes and how
      cells regulate their production of proteins and enzymes. One feature shared among
      living systems is their ability to cope with perturbations and remain stable, a
      property that is the result of evolutionary fine-tuning over many generations. In
      this study we use random Boolean networks (RBNs) as an abstract model of gene
      regulatory systems. By applying Differential Evolution (DE), an evolution-based
      optimization technique, we produce networks with increased stability. DE requires
      relatively few user-specified parameters, has fast convergence and does not rely
      on initial conditions to find the global minima within multi-dimensional search
      spaces. The stability of networks is evaluated by taking parameters such as their
      network sensitivity, attractor cycle length and number of attractor basins into
      account. In this study we present an evolutionary approach to produce networks
      with specific properties (high stability) starting from chaotic regimes. From
      this chaotic regime and randomly generated classical RBNs with static input
      degree, our evolutionary approach is able to produce networks with homogenous
      Boolean functions and highly structured state spaces.

PMID- 19853015
TI  - Preclinical development of a bridging therapy for radiation casualties.
AB  - OBJECTIVE: Victims of a terrorist attack presenting with the hematopoietic
      syndrome resulting from exposure to excessive levels of ionizing radiation will
      succumb to sepsis if not adequately treated. The probability of survival is
      increased substantially if the victim's immune system is allowed to recover
      before sepsis sets in. We report here preclinical development of a new bridging
      therapy that will allow the victim's immune system to recover from damage caused
      by ionizing radiation. MATERIALS AND METHODS: The hematopoietic progenitor cells
      in blood from tocopherol succinate (TS)-injected mice were analyzed
      quantitatively by standard in vitro soft matrix colony procedures. CD2F1 mice
      were irradiated with lethal, whole-body doses (9.2 Gy) of (60)Co gamma-rays and
      then transfused intravenously (periorbital sinus, venous plexus behind the eye)
      with whole blood, peripheral blood mononuclear cells, or plasma from TS-injected
      mice 2 and 24 hours postirradiation. Survival was monitored for 30 days after
      transfusion of whole blood, peripheral blood mononuclear cells, or plasma.
      RESULTS: Progenitor cell analyses revealed that hematopoietic progenitors were
      mobilized into the peripheral blood of TS-injected mice. Our results demonstrated
      that infusions of whole blood or peripheral blood mononuclear cells from TS
      injected mice greatly improved chances of extended survival of lethally
      irradiated mice. CONCLUSION: TS-stimulated granulocyte colony-stimulating factor
      mobilizes high numbers of progenitors into the peripheral circulation; in turn,
      this blood-these progenitors-can be used upon subsequent transfusion to
      effectively mitigate and repair primary acute radiation injury. The transfused
      cells act secondarily as a bridging therapy for irradiated mice while their own
      immune system recovers from the radiation-induced damage.

PMID- 19853017
TI  - Dexamethasone and the inflammatory response in explants of human omental adipose
      tissue.
AB  - Dexamethasone is a synthetic glucocorticoid that is a potent anti-inflammatory
      agent. The present studies examined the changes in gene expression of 64 proteins
      in human omental adipose tissue explants incubated for 48h both in the absence
      and presence of dexamethasone as well as the release of 8 of these proteins that
      are putative adipokines. The proteins were chosen because they are inflammatory
      response proteins in other cells, are key regulatory proteins or are proteins
      with known functions. About 50% were significantly up-regulated while about 10%
      were unchanged and the remaining 40% were down-regulated. Dexamethasone
      significantly up-regulated the expression of about 33% of the proteins but down
      regulated the expression of about 12% of the proteins. We conclude that
      dexamethasone is a selective anti-inflammatory agent since it inhibits only about
      one-fourth of the proteins up-regulated during in vitro incubation of human
      omental adipose tissue.

PMID- 19853018
TI  - Hand dominancy--a feature affecting sensitivity to pain.
AB  - Hand dominancy (i.e. handedness) is a factor that should be considered for
      further characterizing individual variations in sensitivity to pain. The aim of
      the present study was to examine the contribution of handedness and gender to
      sensitivity to tonic cold pain in healthy subjects. Participants were 109 healthy
      volunteers (52 males and 57 females), of whom 65 were right-handed and 44 left
      handed. Subjects were exposed to the cold pressor test (1 degrees C) for both
      hands while measuring the cold pain threshold, intensity, and tolerance. No
      significant differences were found in pain threshold or intensity between the
      right versus the left hands among either the right-handed or the left-handed
      subjects. However, among the right-handed subjects only, cold pain tolerance was
      significantly longer in the right hand than in the left hand (32.9+/-5.1s vs.
      27.0+/-4.2s, respectively; p=0.018). Significant differences were found between
      males and females in pain threshold, but not in pain intensity or tolerance,
      either when their right or left hand was tested (p=0.027 and p=0.009,
      respectively). Analyzing pain perception by handedness and gender revealed that
      the right-handed males were less sensitive to pain in their right versus their
      left hand, as determined by lower pain intensity (p=0.031) and longer tolerance
      (p=0.047). No significant differences were found among the left-handed males or
      among the females. The results provide further evidence that handedness is one
      vital feature that should be considered more often when designing a
      psychophysical study. This may lead towards improving the translation of
      laboratory research findings to the clinical setting.

PMID- 19853019
TI  - p53 mediates nitric oxide-induced apoptosis in murine neural progenitor cells.
AB  - Studies have shown that nitric oxide (NO)-induced apoptosis is mediated by a
      variety of cellular signaling pathways. However, the information is relatively
      limited to neural progenitor cells (NPCs). In this study, the role of p53 in the
      NO-induced apoptosis was examined in an in vitro model of NPCs. Comparisons were
      made between NPCs derived from either wild type or p53 knockout mice brain
      stimulated by diethylenetriamine/nitric oxide adduct (DETA/NO), an established NO
      donor that constantly releases NO through its known first order pharmacological
      kinetics and prolonged half-life. We found that treatment by DETA/NO both time-
      and dose-dependently induced a significant increase of apoptosis in wild type
      NPCs, while p53 knockout NPCs were resistant to the DETA/NO challenge. In
      addition, the DETA/NO-triggered alteration of mitochondrial membrane
      permeability, cleavage of caspase-9/3, and expression of pro-apoptotic Bcl-2
      family members noxa and puma occurred in wild type NPCs but not in p53 knockout
      NPCs. Our current results suggest a central role of p53 in the NO-induced
      apoptotic pathway in NPCs, which may hence provide new insights into the
      regulation of cell death in NPCs that respond to overproduction of NO in injured
      brain.

PMID- 19853020
TI  - Amphetamine and extinction of cued fear.
AB  - Much research is focused on developing novel drugs to improve memory. In
      particular, psychostimulants have been shown to enhance memory and have a long
      history of safe use in humans. In prior work, we have shown that very low doses
      of amphetamine administered before training on a Pavlovian fear-conditioning task
      can dramatically facilitate the acquisition of cued fear. The current experiment
      sought to expand these findings to the extinction of cued fear, a well-known
      paradigm with therapeutic implications for learned phobias and post-traumatic
      stress disorder. If extinction reflects new learning, one might expect drugs that
      enhance the acquisition of cued fear to also enhance the extinction of cued fear.
      This experiment examined whether 0.005 or 0.05 mg/kg of D-amphetamine
      (therapeutic doses shown to enhance acquisition) also enhance the extinction of
      cued fear. Contrary to our hypothesis, amphetamine did not accelerate extinction.
      Thus, at doses that enhance acquisition of conditioned fear, amphetamine does not
      appear to enhance extinction.

PMID- 19853021
TI  - Nonlinearity of coding in primary auditory cortex of the awake ferret.
AB  - Neural computation in sensory systems is often modeled as a linear system. This
      first order approximation is computed by reverse correlating a stimulus with the
      spike train it evokes. The spectro-temporal receptive field (STRF) is a
      generalization of this procedure which characterizes processing in the auditory
      pathway in both frequency and time. While the STRF performs well in predicting
      the overall course of the response to a novel stimulus, it is unable to account
      for aspects of the neural output which are inherently nonlinear (e.g. discrete
      events and non-negative spike rates). We measured the STRFs of neurons in the
      primary auditory cortex (AI) of the awake ferret using spectro-temporally
      modulated auditory gratings, or ripples. We quantified the degree of nonlinearity
      of these neurons by comparing their responses to the responses predicted from
      their respective STRFs. The responses of most cells in AI exhibited a squaring,
      nonlinear relation to the stimuli used to evoke them. Thus, the nonlinearity of
      these cells was nontrivial, that is it was not solely the result of spike rate
      rectification or saturation. By modeling the nonlinearity as a polynomial static
      output function, the predictive power of the STRF was significantly improved.

PMID- 19853022
TI  - Abnormal expressions of glutamate transporters and metabotropic glutamate
      receptor 1 in the spontaneously epileptic rat hippocampus.
AB  - Excessive glutamatergic neurotransmission is considered an underlying factor of
      epilepsy. The modulation of the synaptic activity occurs both by the removal of
      glutamate from the synaptic cleft and by excitatory amino acid transporters
      (EAATs) and by modulation of glutamate receptors. The spontaneously epileptic rat
      (SER), a double mutant (zi/zi, tm/tm), exhibits both tonic convulsions and
      absence-like seizures from the age of 8 weeks. However, there are no reports that
      can elucidate the effects of EAATs and metabotropic glutamate receptors (mGluRs)
      in SER. The present study was undertaken to detect EAATs (GLAST, GLT-1 and EAAC
      1) and Group I metabotropic glutamate receptors (mGluR1) in SER hippocampus from
      both the level of mRNA and protein in SERs hippocampus compared with control
      Wistar rats. In this study, the glutamate concentration in SERs hippocampus was
      increased compared with that of control rats by high performance liquid
      chromatography; the mRNA expressions of GLAST and mGluR1 in SERs hippocampus were
      significantly lower than those in control rats hippocampus, whereas an abundant
      increase in mRNA for GLT-1 was observed by RT-PCR; EAAC-1 and mGluR1 protein in
      SERs and control rats were localized widely in the hippocampus including CA1, CA3
      and dentate gyrus regions by immunohistochemistry; the number of GLAST and mGluR1
      positive cells in the hippocampus of SERs were less than those in control rats,
      especially for CA3 and DG region; the protein expression of GLT-1 was up
      regulated, but the protein expressions of GLAST and mGluR1 were down-regulated in
      SER hippocampus by western blot. Our data show that epileptogenesis in SER are
      associated with regulations of glutamate transporters and mGluR1, which might be
      potential targets for therapy in genetic epilepsy.

PMID- 19853023
TI  - Gender- and age-dependent changes in nucleoside levels in the cerebral cortex and
      white matter of the human brain.
AB  - Nucleosides are neuromodulators that participate in various neuronal functions in
      the brain. In previous studies, we described regional differences in the
      concentrations of nucleosides and their derivatives in the human brain. To better
      understand the functions of nucleosides in the central nervous system, we
      investigated gender- and age-dependent changes in the levels of nucleosides and
      their metabolites. The concentrations of uridine, inosine, guanosine and
      adenosine as well as uracil, hypoxanthine and xanthine were measured in the
      frontal cortex and white matter of post-mortem brain tissue samples of middle
      aged and old men as well as women. The average in vivo concentrations calculated
      from the 40 samples investigated (regardless of anatomical locations, gender or
      age; mean +/- S.E.M.) were as follows (pmol/mg wet tissue weight): 9.7 +/- 0.8
      adenosine, 85.8 +/- 3.9 inosine, 14.3 +/- 0.9 guanosine, 37.3 +/- 1.8 uridine,
      8.9 +/- 0.6 uracil, 63.3 +/- 2.1 hypoxanthine and 38.7 +/- 1.5 xanthine. We
      conclude that concentration differences between uridine, inosine, guanosine and
      adenosine in the frontal cortex and cerebral white matter suggest that nucleoside
      metabolism is altered with aging and regulated differently between men and women.

PMID- 19853024
TI  - Topical application of naltrexone facilitates reepithelialization of the cornea
      in diabetic rabbits.
AB  - Delayed corneal reepithelialization is a complication of diabetes, and may lead
      to ulcers and erosions, which cause ocular morbidity and visual loss. This study
      examined the efficacy of naltrexone (NTX), a long-acting, potent opioid
      antagonist, applied topically, to facilitate the repair of standardized corneal
      abrasions in diabetic (alloxan-induced) New Zealand White rabbits (glucose
      levels>450 mg/dL). NTX at a concentration of 10(-4)M, or sterile vehicle (SV),
      was administered topically 4 times per day for 7 days to the abraded eye of
      uncontrolled Type 1 diabetic (DB), insulin-controlled Type 1 diabetic (DB-IN), or
      non-diabetic (Normal) rabbits. Wound healing was monitored, and non-invasive
      (tonopen, pachymeter, hand-held slit lamp, and retinal camera) and invasive
      (histopathology) measurements evaluated. Corneal reepithelialization in the
      uncontrolled DB rabbits was significantly enhanced (up to a 47% reduction in
      wound area) following treatment with NTX relative to both Normal SV and DB SV
      rabbits at 24, 48, and 56 h following surgery. At 72 h, DB NTX rabbits had
      residual defects that were 64-82% smaller than Normal and DB SV animals. NTX
      treated DB-IN rabbits had residual defects that were 9-37% smaller than DB-IN
      rabbits receiving SV, and 6-40% smaller than Normal rabbits. No signs of toxicity
      from topical applications were noted. These data confirm and extend those
      documented in rats that demonstrated a lack of toxicity of NTX at a wide range of
      dosages, as well as efficacy for enhanced corneal epithelialization. These
      studies set the stage for clinical trials using NTX as a therapy for diabetic
      keratopathy.

PMID- 19853025
TI  - Cd-induced apoptosis was mediated by the release of Ca2+ from intracellular Ca
      storage.
AB  - Previous studies found that cadmium (Cd) could induce apoptosis via interfering
      with the intracellular calcium (Ca) ions homeostasis. But the detailed mechanisms
      remain poorly understood. In the present study two cell lines (normal human liver
      cell HL-7702, and tumor cell Raji cell) were exposed to Cd along or co-incubated
      with ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA)
      and 1,2-bis (2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester
      (BAPTA-AM), respectively. After the incubation, the apoptosis and intracellular
      Ca(2+) ([Ca(2+)](i)) were measured. Excessive apoptosis was observed both in HL
      7702 and Raji cells treated with Cd. Significant elevation of [Ca(2+)](i) was
      also detected in the cells with higher levels of apoptosis. EGTA (the
      extracellular Ca(2+) chelator) decreased Cd-elicited [Ca(2+)](i) (22% in HL-7702
      and 41% in Raji cells; p<0.05) significantly except for apoptosis. However, BAMTA
      AM (the [Ca(2+)](i) chelator) attenuated the Cd-elevated [Ca(2+)](i) (78% in HL
      7702 and 59% in Raji cells; p<0.05) and inhibited Cd-induced apoptosis
      significantly (p<0.05). These results suggest that (1) Ca(2+) was primarily
      generated intracellularly and only a small portion was generated extracellularly;
      (2) Cd-induced apoptosis was mediated by the release of Ca(2+) from intracellular
      Ca storage but not an influx of extracellular Ca(2+).

PMID- 19853026
TI  - Increase the cisplatin cytotoxicity and cisplatin-induced DNA damage in HepG2
      cells by XRCC1 abrogation related mechanisms.
AB  - Cisplatin is one of the most potent chemotherapeutic anticancer drugs for the
      treatment of various cancers. The cytotoxic action of the drug is often thought
      to be associated with its ability to bind DNA to form cisplatin-DNA adducts.
      Impaired DNA repair processes including base excision repair (BER) play important
      roles on its cytotoxicity. XRCC1 is a key protein known to play a central role at
      an early stage in the BER pathway. However, whether XRCC1 contributes to decrease
      the cisplatin cytotoxicity and cisplatin-induced DNA damage in HepG2 still
      remains unknown. Hence, the purpose of this study was to explore whether
      abrogation of XRCC1 gene expression by short hairpin RNAs (shRNA) could reduce
      DNA repair and thus sensitize liver cancer cells to cisplatin. We abrogated the
      XRCC1 gene in HepG2 cell using shRNA transfection. Cell viability was measured by
      MTT assay and clonogenicity assay. Comet assay was used to detect the DNA damage
      induced by cisplatin. The host cell reactivation was employed to assess the DNA
      repair capacity of cisplatin-damaged luciferase reporter plasmid. Flow cytometry
      analysis was used to determine cisplatin-induced apoptosis, cell cycle and
      reactive oxygen species (ROS). The results showed that abrogation of XRCC1 could
      sensitize HepG2 cells to cisplatin. This enhanced cytotoxicity could be
      attributed to the increased DNA damage and reduced DNA repair capacity.
      Increasing cell cycle arrest and intracellular ROS production lead to more tumor
      cell apoptosis and then enhanced the cisplatin cytotoxicity. Our results
      suggested that the cisplatin cytotoxicity may increase by targeting inhibition of
      XRCC1.

PMID- 19853027
TI  - Use of coarse ethylcellulose and PEO in beads produced by extrusion
      spheronization.
AB  - This study evaluated the potential of coarse ethylcellulose (CPEC) and high
      molecular weight polyethylene oxide (PEO) as excipients in the production of
      beads by extrusion-spheronization. CPEC was investigated as a diluent and PEO as
      an extrusion aid and a binder. Beads were manufactured with caffeine as a model
      drug. Release studies were conducted, and the bead size, shape, yield, and
      friability were determined. The effects of formulation and process variables and
      their interactions were studied by a sequential experimental design based on a
      response surface method. In the initial stage, a two level half fractional
      factorial design was employed as a screening design, which was subsequently
      augmented to a central composite design. Statistical analysis indicated that
      formulation variables including PEO content, microcrystalline cellulose (MCC)
      content, and water content, and two process variables, namely spheronizer speed
      and spheronization time, significantly affected the properties of the beads.
      Interactions between two factors have significant effects on several of the
      measured responses. Simultaneous optimization of the responses was conducted and
      validated by performing experiments at the optimal conditions. Overall, the
      results confirmed that immediate release, spherical beads with low friability and
      narrow size distribution could be produced with minimal amounts of MCC.

PMID- 19853028
TI  - Development of inhalable dry powder formulation of basic fibroblast growth
      factor.
AB  - Basic fibroblast growth factor (bFGF) is a promising agent for therapy of asthma
      or chronic obstructive pulmonary disease. We aim to develop an inhalable powder
      formulation of bFGF, which may provide a safe, effective, and convenient way of
      delivering bFGF to the disease-ridden lungs. Development of a bFGF dry powder
      formulation is constrained by the poor stability of bFGF and the uncertainty in
      compatibility of the protein with carrier excipients. With these constraints in
      mind, we prepared dry powders containing bFGF in combinations of albumin,
      phospholipid, lactose, and/or leucine, by spray drying, and evaluated the
      aerodynamic properties of the powders and the stability of bFGF loaded in the
      powders. While an ethanolic solution of phospholipid, albumin, and lactose
      produced dispersible powder, bFGF was unstable in ethanol. The stability of bFGF
      was preserved when spray-dried with lactose in an aqueous solution. Leucine was
      required to obtain dry powder with good dispersibility; however, increase in the
      leucine content more than 50% (w/w) negatively influenced the bFGF stability with
      no additional benefit to the aerodynamic properties of the powders. Dry powders
      containing 20% (w/w) leucine provided desirable aerodynamic properties (fine
      particle fraction of 25.2+/-5.4% and mass median aerodynamic diameter of 4.7+/
      0.9 microm) and 98.1+/-7% recovery of bioactive bFGF. This result warrants
      further investigation of the biological activity of the inhaled bFGF in a disease
      model.

PMID- 19853029
TI  - Multiple roles for the tectorial membrane in the active cochlea.
AB  - This review is concerned with experimental results that reveal multiple roles for
      the tectorial membrane in active signal processing in the mammalian cochlea. We
      discuss the dynamic mechanical properties of the tectorial membrane as a
      mechanical system with several degrees of freedom and how its different modes of
      movement can lead to hair-cell excitation. The role of the tectorial membrane in
      distributing energy along the cochlear partition and how it channels this energy
      to the inner hair cells is described.

PMID- 19853030
TI  - Protective effect of Calotropis procera latex extracts on experimentally induced
      gastric ulcers in rat.
AB  - AIM OF THE STUDY: Calotropis procera is a wild growing plant with multifarious
      medicinal properties. The present study was carried out to evaluate the effect of
      dried latex (DL) of Calotropis procera and its methanol extract (MeDL) against
      gastric ulcers induced in rats. MATERIALS AND METHODS: Aqueous suspension of DL
      (20 and 100mg/kg) and MeDL (10 and 50mg/kg) were given orally to 36h fasted rats
      and ulcers were induced by ethanol, pyloric ligation and aspirin. Parameters like
      ulcer score and levels of oxidative stress markers were measured in all the
      models. The effect on gastric hemorrhage and tissue histology was studied in
      ethanol model and on acidity, pH and volume of gastric secretion was evaluated in
      pyloric ligation model. The protective effect of DL and MeDL was compared with
      that of standard anti-ulcer drug famotidine (20 mg/kg). RESULTS: DL and MeDL
      produced 85-95% inhibition of gastric mucosal damage in ethanol model and 70-80%
      inhibition in aspirin model. The protective effect of these extracts was
      associated with marked reduction in gastric hemorrhage, maintenance of tissue
      integrity and normalization of levels of oxidative stress markers like
      glutathione, thiobarbituric acid reactive substances and superoxide dismutase.
      Like famotidine, DL and MeDL decreased the gastric acidity from 376.17+/-21.47
      mequiv./l to 163.88+/-6.86 and 201.48+/-8.86 mequiv./l respectively in pyloric
      ligation model. These extracts increased the gastric pH without affording any
      protection to gastric mucosa in this model. CONCLUSION: The latex of Calotropis
      procera has the therapeutic potential to relieve gastric hyperacidity and to
      prevent gastric ulceration induced by necrotizing agents.

PMID- 19853031
TI  - Differential susceptibility of inbred mouse strains to Burkholderia thailandensis
      aerosol infection.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis, an emerging
      bacterial disease that accounts for high rates of septicaemia and death in parts
      of Southeast Asia and Northern Australia. The closely related species
      Burkholderia thailandensis is considered avirulent in humans and has been used as
      a surrogate for B. pseudomallei in several studies. The pathogenesis of B.
      pseudomallei and the role of Toll-like receptors (TLRs) in host immunity to
      infection are not well-defined. In this study, we exposed four strains of inbred
      mice (BALB/c, C57BL/6, TLR4-deficient C3H/HeJ, and TLR4-competent C3H/HeN) to
      increasing doses of aerosolized B. thailandensis to determine strain
      susceptibility and the role of TLR4 during pulmonary infection. Our results
      indicate an increased susceptibility in the C57BL/6 and BALB/c strains, who
      displayed lethality, bacterial burden in organs, and pulmonary and systemic
      inflammation. C3H/HeJ were as resistant as C3H/HeN mice to B. thailandensis at
      the highest challenge dose examined, but TLR4-deficient animals exhibited a
      modest increase in chronic pulmonary inflammation. These results demonstrate that
      B. thailandensis can be used as a surrogate for experimental laboratory
      investigation of melioidosis in small animal models and that TLR4 may not play a
      prominent role during acute pneumonic melioidosis.

PMID- 19853032
TI  - Biliary efflux transporters involved in the clearance of rosuvastatin in sandwich
      culture of primary rat hepatocytes.
AB  - Rosuvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) has
      been shown to be excreted mostly unchanged into the bile; interactions on the
      level of hepatic apical efflux transporters may represent a risk of liver
      toxicity. So far, controversial and insufficient data are available concerning
      transporters involved in the elimination process. This study was designed to
      elucidate, which transporters take part in the biliary clearance of rosuvastatin
      using sandwich-cultured primary rat hepatocytes. The canalicular efflux of
      rosuvastatin was measured in the presence of inhibitors: Ko 134, mitoxanthrone,
      novobiocin for breast cancer resistance protein (Bcrp); verapamil for multidrug
      resistance protein (Mdr1); benzbromarone, sulfasalazine, probenecid for multidrug
      resistance associated protein (Mrp 2); and cyclosporine A, glibenclamide,
      troglitazone for bile salt export pump (Bsep). Mrp2 inhibitors decreased the
      biliary efflux of rosuvastatin most potently by 78.9%, 35%, 54.1%; benzbromarone,
      probenecid, sulfasalazine, respectively, while Bcrp and Bsep inhibitors showed
      much less effect (29.1%, 23.0% ,30.0%; Ko 134, mitoxanthrone, novobiocin,
      respectively, and 32.6%, 29.3%, 20.6%, glibenclamide, cyclosporine A,
      troglitazone, respectively). The marked decline of canalicular transport by Mrp2
      inhibitors suggests major role of Mrp2 in this process; however, Bcrp and Bsep
      might also contribute to the biliary elimination of rosuvatatin in sandwich
      cultured rat hepatocytes.

PMID- 19853033
TI  - Intrathecal antibodies and brain damage in autoimmune MRL mice.
AB  - Neuropsychiatric (NP) manifestations and brain pathology are poorly understood
      and potentially fatal concomitants of systemic lupus erythematosus (SLE). For
      many years, autoantibodies to brain tissue (i.e., brain-reactive antibodies, BRA)
      were proposed as a key factor in pathogenesis of CNS manifestations. Recent
      evidence suggests that intrathecal BRA, rather than serum autoantibodies, are a
      better predictor of disturbed brain morphology and function. We presently test
      this hypothesis by examining the relationship among BRA in cerebrospinal fluid
      (CSF), behavioral deficits, and brain pathology in a well-established animal
      model of CNS lupus. We showed earlier that significant diversity in disease
      manifestations within genetically homogenous MRL-lpr mice allows for constructive
      and informative correlational analysis. Therefore, levels of CSF antibodies were
      presently correlated with behavioral, neuropathological and immune measures in a
      cohort of diseased MRL-lpr males (N=40). ELISA, Western Blotting, standardized
      behavioral battery, digital planimetry, HE staining, and immunohistochemistry
      were employed in overall data collection. The IgG antibodies from CSF were
      binding to different regions of brain parenchyma, with dentate gyrus, amygdale,
      and subventricular zones showing enhanced immunoreactivity. High levels of CSF
      antibodies correlated with increased immobility in the forced-swim test and
      density of HE(+) cells in the paraventricular nucleus. Peripheral measures of
      autoimmunity were associated with other deficits in behavior and neuropathology.
      This correlation pattern suggests that etiology of brain damage in lupus-prone
      mice is multifactorial. Intrathecal BRA may be important in altering motivated
      responses and activity of major neuroendocrine axes at the onset of SLE-like
      disease.

PMID- 19853035
TI  - Involvement of Dab1 in APP processing and beta-amyloid deposition in sporadic
      Creutzfeldt-Jakob patients.
AB  - Alzheimer's disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD))
      display profound neural lesions associated with aberrant protein processing and
      extracellular amyloid deposits. Dab1 has been implicated in the regulation of
      amyloid precursor protein (APP), but a direct link between human prion diseases
      and Dab1/APP interactions has not been published. Here we examined this putative
      relationship in 17 cases of sporadic CJD (sCJD) post-mortem. Biochemical analyses
      of brain tissue revealed two groups, which also correlated with PrP(sc) types 1
      and 2. One group with PrP(sc) type 1 showed increased Dab1 phosphorylation and
      lower betaCTF production with an absence of Abeta deposition. The second sCJD
      group, which carried PrP(sc) type 2, showed lower levels of Dab1 phosphorylation
      and betaCTF production, and Abeta deposition. Thus, the present observations
      suggest a correlation between Dab1 phosphorylation, Abeta deposition and PrP(sc)
      type in sCJD.

PMID- 19853034
TI  - Neonatal dexamethasone treatment leads to alterations in cell signaling cascades
      controlling hepatic and cardiac function in adulthood.
AB  - Increasing evidence indicates that early-life glucocorticoid exposure, either
      involving stress or the therapy of preterm labor, contributes to metabolic and
      cardiovascular disorders in adulthood. We investigated cellular mechanisms
      underlying these effects by administering dexamethasone (DEX) to neonatal rats on
      postnatal (PN) days 1-3 or 7-9, using doses spanning the threshold for somatic
      growth impairment: 0.05, 0.2 and 0.8 mg/kg. In adulthood, we assessed the effects
      on hepatic and cardiac cell function mediated through the adenylyl cyclase (AC)
      signaling cascade, which controls neuronal and hormonal inputs that regulate
      hepatic glucose metabolism and cardiac contractility. Treatment on PN1-3 produced
      heterologous sensitization of hepatic signaling, with upregulation of AC itself
      leading to parallel increases in the responses to beta-adrenergic or glucagon
      receptor stimulation, or to activation of G-proteins by fluoride. The effects
      were seen at the lowest dose but increasing DEX past the point of somatic growth
      impairment led to loss of the effect in females. Nonmonotonic effects were also
      present in the heart, where males showed AC sensitization at the lowest dose,
      with decreasing effects as the dose was raised; females showed progressive
      deficits of cardiac AC activity. Shifting the exposure to PN7-9 still elicited AC
      sensitization but with a greater offsetting contribution at the higher doses. Our
      findings show that, in contrast to growth restriction, the glucocorticoids
      associated with stress or the therapy of preterm labor are more sensitive and
      more important contributors to the cellular abnormalities underlying subsequent
      metabolic and cardiovascular dysfunction.

PMID- 19853036
TI  - Ablation of TrpV1 neurons reveals their selective role in thermal pain sensation.
AB  - Here we make use of neural ablation to investigate the properties of the TrpV1
      expressing neurons in the trigeminal and dorsal root ganglia of mice.
      Resiniferotoxin (RTX), a potent TrpV1 agonist, administered either by direct
      injection in the ganglion or intrathecally killed approximately 70% of TrpV1
      cells and resulted in modest thermal analgesia. Interestingly, after carageenan
      injection in the hind paw, the analgesic effects of RTX were dramatically
      increased with mice now paradoxically showing far less response to heat applied
      at sites of inflammation. This additional carageenan and RTX-induced analgesia
      was transient, lasting less than 2 days, and likely resulted from deafferentation
      of remaining TrpV1 neurons. Remarkably, although RTX affected sensitivity to
      heat, mechanical sensitivity (both of normal and inflamed tissue) was completely
      unaltered by toxin-mediated silencing of the TrpV1 sensory input. Thus, our data
      demonstrate that TrpV1 neurons are selectively tuned nociceptors that mediate
      responses to thermal but not mechanical pain and insinuate a labeled line model
      for somatosensory coding.

PMID- 19853037
TI  - Refolding active human DNA polymerase nu from inclusion bodies.
AB  - Human DNA polymerase nu (Pol nu) is a conserved family A DNA polymerase of
      uncertain biological function. Physical and biochemical characterization aimed at
      understanding Pol nu function is hindered by the fact that, when over-expressed
      in Escherichia coli, Pol nu is largely insoluble, and the small amount of soluble
      protein is difficult to purify. Here we describe the use of high hydrostatic
      pressure to refold Pol nu from inclusion bodies, in soluble and active form. The
      refolded Pol nu has properties comparable to those of the small amount of Pol nu
      that was purified from the soluble fraction. The approach described here may be
      applicable to other DNA polymerases that are expressed as insoluble inclusion
      bodies in E. coli.

PMID- 19853038
TI  - Crystal structure of Hyp-1, a St. John's wort protein implicated in the
      biosynthesis of hypericin.
AB  - Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in
      the medicinal plant Hypericum perforatum, widely known as St. John's wort.
      Hypericin has been attracting a growing attention of the pharmaceutical industry
      because of its potential application in various therapies, including the
      treatment of depression. In vivo, hypericin is synthesized by dimerization of
      emodin in a complicated multistep reaction that is reportedly catalyzed by a
      small (17.8kDa) protein, Hyp-1. Based on relatively low sequence similarity (
      approximately 50%), Hyp-1 has been tentatively classified as a plant PR-10
      (pathogenesis-related class 10) protein. Members of the PR-10 family are
      ubiquitous plant proteins associated with stress control and tissue
      differentiation but with no clearly understood molecular mechanism. They have,
      however, a well-defined folding canon, consisting of an extended antiparallel
      beta-sheet wrapped around a C-terminal alpha-helix, enclosing in the protein
      interior a huge cavity, in which various hydrophobic ligands can be bound. Apart
      from Hyp-1, only two other PR-10 members have been found to possess enzymatic
      activity (S-norcoclaurine synthase and TcmN aromatase/cyclase). In this paper, we
      report a high-resolution crystal structure of Hyp-1, confirming that it indeed
      has a PR-10 fold. The protein binds multiple polyethylene glycol molecules, some
      of which occupy the hydrophobic cavity. The crystallographic model illustrates a
      high degree of conformational adaptability of both interacting partners for
      efficient binding. We have been unable, however, to dimerize emodin to hypericin
      using Hyp-1 as biocatalyst. This puzzling result does not have a clear
      explanation at this time.

PMID- 19853039
TI  - Functional immune response in Pecten maximus: combined effects of a pathogen
      associated molecular pattern and PAH exposure.
AB  - Pathogen-associated molecular patterns (PAMPs) enable recognition of structures
      present in microorganisms such as lipopolysaccharides (LPS). LPS are an essential
      constituent of the outer membrane of Gram-negative bacteria, stimulating the
      innate immune system of invertebrates. Here, LPS from Escherichia coli (055:B5)
      were used to investigate the functional immune response of Pecten maximus after
      stimulation with a PAMP and to determine the combined effect of a phenanthrene
      exposure and LPS challenge. Organisms were exposed to 200 mug l(-1) phenanthrene
      and after 7 d were injected with either physiological saline (injection controls)
      or LPS solution, and returned to their respective exposure tanks. Haemolymph was
      sampled from the scallops 48 h post-injection and immune function was assessed
      using a combination of cellular biological responses. The LPS challenge
      significantly altered the immune response in P. maximus with increased cell
      counts and phagocytic activity. An immunosuppressive effect of phenanthrene was
      also observed in this study; however, exposure to phenanthrene did not
      significantly impair the organism's ability to respond to a PAMP challenge. The
      overall level of phagocytosis and cytotoxic capability following the LPS
      challenge was lower in phenanthrene exposed scallops and may have consequences
      for disease resistance in this commercially-exploited species.

PMID- 19853040
TI  - Right-hemispheric brain activation correlates to language performance.
AB  - Language function in the right-hemispheric homologues of Broca's and Wernicke's
      areas does not only correlate with left-handedness or pathology, but occurs
      naturally in right-handed healthy subjects as well. In the current study, two non
      invasive methods of assessing language lateralization are correlated with
      behavioral results in order to link hemispheric dominance to language ability in
      healthy subjects. Functional magnetic resonance imaging (fMRI) together with a
      sentence-completion paradigm was used to determine region-specific lateralization
      indices in the left- and right-sided Broca's and Wernicke's areas, the frontal
      temporal lobe, the anterior cingulate cortex and the parietal lobe. In addition,
      dichotic listening results were used to determine overall language lateralization
      and to strengthen conclusions by correlating with fMRI indices. Results showed
      that fMRI lateralization in the superior parietal, the posterior temporal, and
      the anterior cingulate cortices correlated to dichotic listening. A decreased
      right ear advantage (REA), which indicates less left-hemispheric dominance in
      language, correlated with higher performance in most administered language tasks,
      including reading, language ability, fluency, and non-word discrimination.
      Furthermore, right hemispheric involvement in the posterior temporal lobe and the
      homologue of Broca's area suggests better performance in behavioral language
      tasks. This strongly indicates a supportive role of the right-hemispheric
      counterparts of Broca's and Wernicke's areas in language performance.

PMID- 19853041
TI  - Physical activity and memory functions: are neurotrophins and cerebral gray
      matter volume the missing link?
AB  - Epidemiological studies reveal better cognitive function in physically active
      individuals. Possible mediators for this effect are neurotrophins, which are up
      regulated through physical exercise and induce neuronal growth and synaptogenesis
      in the animal model. Here we cross-sectionally assessed 75 healthy older
      individuals for levels of physical activity, aerobic fitness, and memory
      encoding, as well as neurotrophin levels and cerebral gray matter volume. We
      found that physical activity, but not cardiovascular fitness, was associated with
      better memory encoding after controlling for age, sex, education, depression,
      alcohol consumption, and smoking. Higher levels of physical activity were
      associated with higher levels of the neurotrophin granulocyte colony stimulating
      factor (G-CSF) and increased cerebral gray matter volume in prefrontal and
      cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While
      mediating factors will need to be further elucidated, these findings indicate
      that even low-level physical activity exerts beneficial effects on memory
      functions in older individuals.

PMID- 19853042
TI  - A mean three-dimensional atlas of the human thalamus: generation from multiple
      histological data.
AB  - Functional neurosurgery relies on robust localization of the subcortical target
      structures, which cannot be visualized directly with current clinically available
      in-vivo imaging techniques. Therefore, one has still to rely on an indirect
      approach, by transferring detailed histological maps onto the patient's
      individual brain images. In contrast to macroscopic MRI atlases, which often
      represent the average of a population, each stack of sections, which a
      stereotactic atlas provides, is based on a single specimen. In addition to this
      bias, the anatomy is displayed with a highly anisotropic resolution, leading to
      topological ambiguities and limiting the accuracy of geometric reconstruction. In
      this work we construct an unbiased, high-resolution three-dimensional atlas of
      the thalamic structures, representing the average of several stereotactically
      oriented histological maps. We resolve the topological ambiguity by combining the
      information provided by histological data from different stereotactic directions.
      Since the stacks differ not only in geometrical detail provided, but also due to
      inter-individual variability, we adopt an iterative approach for reconstructing
      the mean model. Starting with a reconstruction from a single stack of sections,
      we iteratively register the current reference model onto the available data and
      reconstruct a refined mean three-dimensional model. The results show that
      integration of multiple stereotactic anatomical data to produce an unbiased, mean
      model of the thalamic nuclei and their subdivisions is feasible and that the
      integration reduces problems of atlas reconstruction inherent to histological
      stacks to a large extent.

PMID- 19853043
TI  - Gradual inversion affects the processing of human body shapes.
AB  - Inversion (rotation around 180 degrees ) impairs body recognition and affects
      early electrophysiological responses (especially the N170). However, the
      relationship between electrophysiological responses and behavior is as yet
      unclear. Furthermore, the presence of the head seems to have an impact on body
      recognition performances as well as on related electrophysiological responses.
      The present study aimed to investigate the course of behavioral and
      electrophysiological body inversion effects depending upon the degree of
      deviation from the upright position (0 degrees , 360 degrees ) to the inverted
      position (180 degrees ). Body stimuli were presented either with heads (masked
      face) or without heads in a delayed matching task. For human bodies presented
      with and without heads, there was a quadratic relationship between the angle of
      rotation and the behavioral performance as well as the N170 amplitude, with
      maximum performance disruption at 180 degrees deviation from the upright
      stimulus. The data indicate that configural body processing occurs during the
      structural encoding of body stimuli.

PMID- 19853045
TI  - The current state, challenges and perspectives of MR-PET.
AB  - Following the success of PET/CT during the last decade and the recent increasing
      proliferation of SPECT/CT, another hybrid imaging instrument has been gaining
      more and more interest: MR-PET. First combined, simultaneous PET and MR studies
      carried out in small animals demonstrated the feasibility of the new approach.
      Concurrently, some prototypes of an MR-PET scanner for simultaneous human brain
      studies have been built, their performance is being tested and preliminary
      applications have already been shown. Through this pioneering work, it has become
      clear that advances in the detector design are necessary for further
      optimization. Recently, the different issues related to the present state and
      future prospects of MR-PET were presented and discussed during an international 2
      day workshop at the Forschungszentrum Julich, Germany, held after, and in
      conjunction with, the 2008 IEEE Nuclear Science Symposium and Medical Imaging
      Conference in Dresden, Germany on October 27-28, 2008. The topics ranged from
      small animal MR-PET imaging to human MR-BrainPET imaging, new detector
      developments, challenges/opportunities for ultra-high field MR-PET imaging and
      considerations of possible future research and clinical applications. This report
      presents a critical summary of the contributions made to the workshop.

PMID- 19853046
TI  - The causal role of category-specific neuronal representations in the left ventral
      premotor cortex (PMv) in semantic processing.
AB  - The left ventral premotor cortex (PMv) is preferentially activated by exemplars
      of tools, suggestive of category specificity in this region. Here we used state
      dependent transcranial magnetic stimulation (TMS) to investigate the causal role
      of such category-specific neuronal representations in the encoding of tool words.
      Priming to a category name (either "Tool" or "Animal") was used with the
      objective of modulating the initial activation state of this region prior to
      application of TMS and the presentation of the target stimulus. When the target
      word was an exemplar of the "Tool" category, the effects of TMS applied over PMv
      (but not PMd) interacted with priming history by facilitating reaction times on
      incongruent trials while not affecting congruent trials. This congruency/TMS
      interaction implies that the "Tool" and "Animal" primes had a differential effect
      on the initial activation state of the left PMv and implies that this region is
      one neural locus of category-specific behavioral priming for the "Tool" category.
      TMS applied over PMv had no behavioral effect when the target stimulus was an
      exemplar of the "Animal" category, regardless of whether the target word was
      congruent or incongruent with the prime. That TMS applied over the left PMv
      interacted with a priming effect that extended from the category name ("Tool") to
      exemplars of that category suggests that this region contains neuronal
      representation associated with a specific semantic category. Our results also
      demonstrate that the state-dependent effects obtained in the combination of
      visual priming and TMS are useful in the study of higher-level cognitive
      functions.

PMID- 19853044
TI  - Imaging serotonergic transmission with [11C]DASB-PET in depressed and non
      depressed patients infected with HIV.
AB  - INTRODUCTION: Site-selective imaging can provide significant insight into the
      mechanism of HIV-associated neurological disease. The goal of this study was to
      evaluate the involvement of serotonergic transmission in HIV-associated
      depression using [(11)C]DASB, a serotonin transporter (5-HTT)-specific
      radiopharmaceutical for positron emission tomography (PET). METHODS: Nine
      depressed HIV+ subjects (HIV-D), 9 non-depressed HIV+ subjects (HIV-ND) and 7
      healthy controls (HC) underwent an MRI scan and a [(11)C]DASB-PET scan. The
      outcome measure was 5-HTT binding potential normalized to non-displaceable tissue
      radioligand (BP(ND)). RESULTS: HIV-ND subjects had lower mean regional 5-HTT
      BP(ND) estimates across regions compared to HC, while HIV-D subjects demonstrated
      higher mean regional binding values than HIV-ND subjects in most regions. Prior
      to correction for the false discovery rate, HIV-ND had significantly lower BP(ND)
      values compared to HC subjects in two regions (insula and anterior cingulate) and
      all HIV+ patients had significantly lower binding than HC in all regions except
      for the midbrain, thalamus and pons. After correction for the false discovery
      rate, only the insula showed significantly lower binding in HIV+ subjects
      compared to HC (P<0.0045). Despite a significant difference in the duration of
      illness between the HIV-D and HIV-ND groups, there was no definite correlation
      between the duration of illness and BP(ND). CONCLUSION: Lower [(11)C]DASB binding
      in HIV+ patients compared to HC may reflect serotonergic neuronal loss as a
      component of generalized HIV-associated neurodegeneration. Higher mean regional
      BP(ND) values in HIV-D compared to HIV-ND subjects could reflect increased
      density of 5-HTT, leading to increased clearance of serotonin from the synapse,
      which could account, in part, for symptoms of depression. The lack of correlation
      between duration of illness and binding argues against these findings being the
      result of differential neurodegeneration only. Our findings suggest a possible
      role for dysregulated serotonergic transmission in HIV-associated depression.

PMID- 19853047
TI  - Feature-based morphometry: discovering group-related anatomical patterns.
AB  - This paper presents feature-based morphometry (FBM), a new fully data-driven
      technique for discovering patterns of group-related anatomical structure in
      volumetric imagery. In contrast to most morphometry methods which assume one-to
      one correspondence between subjects, FBM explicitly aims to identify distinctive
      anatomical patterns that may only be present in subsets of subjects, due to
      disease or anatomical variability. The image is modeled as a collage of generic,
      localized image features that need not be present in all subjects. Scale-space
      theory is applied to analyze image features at the characteristic scale of
      underlying anatomical structures, instead of at arbitrary scales such as global
      or voxel-level. A probabilistic model describes features in terms of their
      appearance, geometry, and relationship to subject groups, and is automatically
      learned from a set of subject images and group labels. Features resulting from
      learning correspond to group-related anatomical structures that can potentially
      be used as image biomarkers of disease or as a basis for computer-aided
      diagnosis. The relationship between features and groups is quantified by the
      likelihood of feature occurrence within a specific group vs. the rest of the
      population, and feature significance is quantified in terms of the false
      discovery rate. Experiments validate FBM clinically in the analysis of normal
      (NC) and Alzheimer's (AD) brain images using the freely available OASIS database.
      FBM automatically identifies known structural differences between NC and AD
      subjects in a fully data-driven fashion, and an equal error classification rate
      of 0.80 is achieved for subjects aged 60-80 years exhibiting mild AD (CDR=1).

PMID- 19853048
TI  - Prefrontal hemodynamic changes produced by anodal direct current stimulation.
AB  - Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation
      technique that has been investigated for the treatment of many neurological or
      neuropsychiatric disorders. Its main effect is to modulate the cortical
      excitability depending on the polarity of the current applied. However,
      understanding the mechanisms by which these modulations are induced and persist
      is still an open question. A possible marker indicating a change in cortical
      activity is the subsequent variation in regional blood flow and metabolism. These
      variations can be effectively monitored using functional near-infrared
      spectroscopy (fNIRS), which offers a noninvasive and portable measure of regional
      blood oxygenation state in cortical tissue. We studied healthy volunteers at rest
      and evaluated the changes in cortical oxygenation related to tDCS using fNIRS.
      Subjects were tested after active stimulation (12 subjects) and sham stimulation
      (10 subjects). Electrodes were applied at two prefrontal locations; stimulation
      lasted 10 min and fNIRS data were then collected for 20 min. The anodal
      stimulation induced a significant increase in oxyhemoglobin (HbO(2))
      concentration compared to sham stimulation. Additionally, the effect of active 10
      min tDCS was localized in time and lasted up to 8-10 min after the end of the
      stimulation. The cathodal stimulation manifested instead a negligible effect. The
      changes induced by tDCS on HbO(2), as captured by fNIRS, agreed with the results
      of previous studies. Taken together, these results help clarify the mechanisms
      underlying the regional alterations induced by tDCS and validate the use of fNIRS
      as a possible noninvasive method to monitor the neuromodulation effect of tDCS.

PMID- 19853049
TI  - A molecular phylogeny shows the single origin of the Pyrenean subterranean
      Trechini ground beetles (Coleoptera: Carabidae).
AB  - Trechini ground beetles include some of the most spectacular radiations of cave
      and endogean Coleoptera, but the origin of the subterranean taxa and their
      typical morphological adaptations (loss of eyes and wings, depigmentation,
      elongation of body and appendages) have never been studied in a formal
      phylogenetic framework. We provide here a molecular phylogeny of the Pyrenean
      subterranean Trechini based on a combination of mitochondrial (cox1, cyb, rrnL,
      tRNA-Leu, nad1) and nuclear (SSU, LSU) markers of 102 specimens of 90 species. We
      found all Pyrenean highly modified subterranean taxa to be monophyletic, to the
      exclusion of all epigean and all subterranean species from other geographical
      areas (Cantabrian and Iberian mountains, Alps). Within the Pyrenean subterranean
      clade the three genera (Geotrechus, Aphaenops and Hydraphaenops) were
      polyphyletic, indicating multiple origins of their special adaptations to
      different ways of life (endogean, troglobitic or living in deep fissures).
      Diversification followed a geographical pattern, with two main clades in the
      western and central-eastern Pyrenees respectively, and several smaller lineages
      of more restricted range. Based on a Bayesian relaxed-clock approach, and using
      as an approximation a standard mitochondrial mutation rate of 2.3% MY, we
      estimate the origin of the subterranean clade at ca. 10 MY. Cladogenetic events
      in the Pliocene and Pleistocene were almost exclusively within the same
      geographical area and involving species of the same morphological type.

PMID- 19853050
TI  - Phylogeography of Helleria brevicornis (Crustacea, Oniscidea): old and recent
      differentiations of an ancient lineage.
AB  - Helleria brevicornis has a disjunct, peri-Tyrrhenian distribution that mirrors
      that of several organisms, for which geographic vicariance is invoked, due to the
      geological events started with the Oligocene split of the Sardo-Corsican
      microplate from the Pyrenees, and successive separation between Sardinia and
      Corsica. Molecular phylogenetic analyses demonstrated that such a biogeographic
      model does not apply to Helleria. The original split of the Sardinian and
      Corsican lineages originated in the Early Pliocene. Further diversification
      occurred later. The colonization of the Tuscan archipelago, French, and Italian
      mainland occurred most recently, but a possible time dependency bias suggests
      that such colonization was driven by human-transport.

PMID- 19853051
TI  - Evolutionary inferences based on ITS rDNA and actin sequences reveal extensive
      diversity of the common lichen alga Asterochloris (Trebouxiophyceae,
      Chlorophyta).
AB  - The genus Asterochloris is one of the most common lichen photobionts. We present
      a molecular investigation of 41 cultured strains, for which nuclear-encoded ITS
      rDNA and partial actin I sequences were determined. The loci studied revealed
      considerable differences in their evolutionary dynamics as well as sequence
      variation. As compared to ITS data, the actin sequences show much greater
      variation, and the phylogenies yield strong resolution and support of many
      internal branches. The partitioning of ITS dataset into several regions yielded
      better node resolution. We recognized 16 well-supported monophyletic lineages, of
      which one represents the type species of the genus (Asterochloris phycobiontica),
      and six correspond to species previously classified to the genus Trebouxia (T.
      erici, T. excentrica, T. glomerata, T. irregularis, T. italiana and T. magna).
      Only 15% of isolated photobionts considered in our study could be assigned with
      certainty to previously described species, emphasizing amazing cryptic
      variability in Asterochloris. Concurrently with the formal delimitation of the
      genus Asterochloris, we propose new combinations for the former Trebouxia
      species; furthermore, T. pyriformis is reduced to a synonym of A. glomerata. The
      present knowledge of global diversity of Asterochloris algae is discussed.

PMID- 19853053
TI  - On the value of Elongation factor-1alpha for reconstructing pterygote insect
      phylogeny.
AB  - Pterygota are traditionally divided in two lineages, the "Palaeoptera" and
      Neoptera. Despite several efforts neither morphology nor molecular systematics
      have resolved the phylogeny of the pterygote insects. Too few markers have yet
      been identified for adequately tracking mesozoic-aged divergences. We tested the
      Elongation factor-1alpha for its phylogenetic value in pterygote insect
      systematics. This highly conserved nuclear protein-coding gene has previously
      been reported to be useful in other groups for phylogenetic analyses at the
      intraordinal level as well as at the interordinal level. The analyses suggest
      that EF-1alpha DNA sequences as well as intron positions provide informative
      markers for pterygote phylogenetics.

PMID- 19853052
TI  - The phylogeny of mosses - addressing open issues with a new mitochondrial locus:
      group I intron cobi420.
AB  - Mosses are an ancient clade of land plants, set apart from the two other
      monophyletic groups of bryophytes, the liverworts and the hornworts. Different
      molecular data sets seem to converge towards a consensus backbone phylogeny of
      mosses. Nevertheless, for some crucial nodes open questions remain, which
      obviously require additional phylogenetic information. We here report that a
      group I intron in the mitochondrial cob gene (cobi420) is universally conserved
      in the mosses, including basal genera such as Sphagnum and Takakia. Well resolved
      phylogenetic trees were obtained for 56 mosses of wide phylogenetic sampling,
      e.g. supporting a placement of Drummondia branching after the genera Timmiella
      and Catoscopium basal in the Dicranidae. Taxon gaps have been filled in the
      previously established data sets nad5i753, nad2i156, the nad5-nad4 intergenic
      region and chloroplast rbcL and rps4 genes. A concatenated 6-loci analysis
      suggests reconsideration of a Funariidae concept which includes Gigaspermaceae
      but leaves the isolated genus Timmia at the radiation of arthrodontous mosses
      unresolved.

PMID- 19853054
TI  - Evolution of a multifunctional gene: The warm temperature acclimation protein
      Wap65 in the European seabass Dicentrarchus labrax.
AB  - The warm temperature acclimation protein Wap65 has been shown to be involved in
      temperature acclimation, in immune response as well as in development. In
      teleosts, two types of Wap65 proteins, Wap65-1 and Wap65-2 are found, both acting
      as a multifunctional agent in several biological processes. In the present study
      we identified both transcripts Wap65-1 and Wap65-2 for the European seabass
      (Dicentrarchus labrax), examined their evolutionary rate and performed selection
      tests. The two paralogues were shown to be under moderate positive selection
      indicating their evolutionary adaptation. This functional diversification was
      further explored through expression studies. Both transcripts were differentially
      expressed during development as well as in various tissues and pathogen
      challenges, showing that Wap65-1 and Wap65-2 have evolved diverse functions.
      These results direct to the hypothesis that Wap65 proteins may, similarly to heat
      shock proteins, have a general role in cell physiology.

PMID- 19853055
TI  - Rapid radiation, ancient incomplete lineage sorting and ancient hybridization in
      the endemic Lake Tanganyika cichlid tribe Tropheini.
AB  - The evolutionary history of the endemic Lake Tanganyika cichlid tribe Tropheini,
      the sister group of the species flocks of Lake Malawi and the Lake Victoria
      region, was reconstructed from 2009 bp DNA sequence of two mitochondrial genes
      (ND2 and control region) and from 1293 AFLP markers. A period of rapid
      cladogenesis at the onset of the diversification of the Tropheini produced a
      multitude of specialized, predominantly rock-dwelling aufwuchs-feeders that now
      dominate in Lake Tanganyika's shallow habitat. Nested within the stenotopic rock
      dwellers is a monophyletic group of species, which also utilize more sediment
      rich habitat. Most of the extant species date back to at least 0.7 million years
      ago. Several instances of disagreement between AFLP and mtDNA tree topology are
      attributed to ancient incomplete lineage sorting, introgression and
      hybridization. A large degree of correspondence between AFLP clustering and
      trophic types indicated fewer cases of parallel evolution of trophic
      ecomorphology than previously inferred from mitochondrial data.

PMID- 19853056
TI  - Learning strategy trumps motivational level in determining learning-induced
      auditory cortical plasticity.
AB  - Associative memory for auditory-cued events involves specific plasticity in the
      primary auditory cortex (A1) that facilitates responses to tones which gain
      behavioral significance, by modifying representational parameters of sensory
      coding. Learning strategy, rather than the amount or content of learning, can
      determine this learning-induced cortical (high order) associative
      representational plasticity (HARP). Thus, tone-contingent learning with signaled
      errors can be accomplished either by (1) responding only during tone duration
      ("tone-duration" strategy, T-Dur), or (2) responding from tone onset until
      receiving an error signal for responses made immediately after tone offset ("tone
      onset-to-error", TOTE). While rats using both strategies achieve the same high
      level of performance, only those using the TOTE strategy develop HARP, viz.,
      frequency-specific decreased threshold (increased sensitivity) and decreased
      bandwidth (increased selectivity) (Berlau & Weinberger, 2008). The present study
      challenged the generality of learning strategy by determining if high motivation
      dominates in the formation of HARP. Two groups of adult male rats were trained to
      bar-press during a 5.0kHz (10s, 70dB) tone for a water reward under either high
      (HiMot) or moderate (ModMot) levels of motivation. The HiMot group achieved a
      higher level of correct performance. However, terminal mapping of A1 showed that
      only the ModMot group developed HARP, i.e., increased sensitivity and selectivity
      in the signal-frequency band. Behavioral analysis revealed that the ModMot group
      used the TOTE strategy while HiMot subjects used the T-Dur strategy. Thus, type
      of learning strategy, not level of learning or motivation, is dominant for the
      formation of cortical plasticity.

PMID- 19853058
TI  - Nonclinical development of biopharmaceuticals.
AB  - The nonclinical development plan (NDP) for biotechnology-derived pharmaceuticals
      (biologics) as addressed in this review comprises aspects of nonclinical drug
      safety (toxicology and safety pharmacology), nonclinical pharmacokinetics (PKs)
      and nonclinical and clinical bioanalytics. A variety of bioanalytical methods are
      needed to describe PK behavior and to monitor immune response in laboratory
      animals and humans. The NDP will often differ from established programs for small
      molecules to account for target differences, a lack of or limited species
      crossreactivity and/or the limited applicability of long-term studies, as well as
      immunogenicity assessment. Special study designs, scientifically justified and
      driven by a case-by-case approach, might overcome these hurdles.

PMID- 19853057
TI  - The Botrytis cinerea aspartic proteinase family.
AB  - The ascomycete plant pathogen Botrytis cinerea secretes aspartic proteinase (AP)
      activity. Functional analysis was carried out on five aspartic proteinase genes
      (Bcap1-5) reported previously. Single and double mutants lacking these five genes
      showed neither a reduced secreted proteolytic activity, nor a reduction in
      virulence and they showed no alteration in sensitivity to antifungal proteins
      purified from grape juice. Scrutiny of the B. cinerea genome revealed the
      presence of nine additional Bcap genes, denoted Bcap6-14. The product of the
      Bcap8 gene was found to constitute up to 23% of the total protein secreted by B.
      cinerea. Bcap8-deficient mutants secreted approximately 70% less AP activity but
      were just as virulent as the wild-type strain. Phylogenetic analysis showed that
      Bcap8 has orthologs in many basidiomycetes but only few ascomycetes including the
      biocontrol fungus Trichoderma harzanium. Potential functions of the 14 APs in B.
      cinerea are discussed based on their sequence characteristics, phylogeny and
      predicted localization.

PMID- 19853059
TI  - Clinical prediction rules: new opportunities for pharma.
AB  - Clinical prediction rules (CPRs) are important tools in the development of an
      evidence-based, personalized medical system. This article compares CPRs to other
      medical information tools, giving solvent examples of their clinical application
      and potential to increase efficacy and efficiency, as well as their utility in
      drug development. The primary focus is on the potential of CPRs to define the
      most effective level of generalization, predictably and reproducibly identifying
      homogenous groups of subjects (based on outcome) in heterogeneous and
      undifferentiated trial populations. This potential can be met if CPR construction
      integrates three elements: the identification of variables both within and
      outside the disorder that affect outcome and the mapping of relevant human
      physiome types based upon identifiable trait and reactionary patterns.

PMID- 19853060
TI  - Surrogate approaches in development of monoclonal antibodies.
AB  - When cross-reactivity of a lead antibody across species is limited, antibody
      development programs require the generation of surrogate molecules or surrogate
      animal models necessary for the conduct of preclinical pharmacology and safety
      studies. When surrogate approaches are employed, the complexities and challenges
      for translation of preclinical safety and efficacy results to the clinic are
      undoubtedly enhanced. Because there are no currently established criteria or
      regulatory guidance regarding the application of surrogate approaches, a science
      based strategy for translation of preclinical information to the clinic is vital
      for effective development of the lead antibody.

PMID- 19853061
TI  - Phenotype and functions of spleen dendritic cells in RICK-knockout mice.
AB  - RICK (receptor-interacting caspase-like apoptosis-regulatory kinase), a protein
      kinase, promotes nuclear factor kappa B and caspase activation. Herein, in order
      to further learn the immune role of RICK, its gene in mice was knocked out. Then
      the phenotype, cytokine, endocytosis and stimulatory capacity of spleen dendritic
      cells (SDCs) from RICK(-) (knockout) and RICK(+) (wild type) mice were analyzed.
      Our results showed that the levels of I-Ad, CD11b, CD80 on SDCs from RICK(-) mice
      were higher while the levels of CD8alpha, CD40, CD45R were lower compared with
      those from RICK(+) mice; The intracellular levels of IL-4, IL-10, IL-12, IFN
      gamma, and TNF-alpha in SDCs from RICK(-) mice were higher than those from
      RICK(+) mice; The endocytosis and stimulatory capacities of SDCs from RICK(-)
      mice were higher and lower than those from RICK(+) mice respectively. These data
      suggested that RICK had a profound influence on the maturation and functions of
      murine SDCs and subsequently regulated the organ immune responses.

PMID- 19853062
TI  - Caloric restriction: from soup to nuts.
AB  - Caloric restriction (CR), reduced protein, methionine, or tryptophan diets; and
      reduced insulin and/or IGFI intracellular signaling can extend mean and/or
      maximum lifespan and delay deleterious age-related physiological changes in
      animals. Mice and flies can shift readily between the control and CR
      physiological states, even at older ages. Many health benefits are induced by
      even brief periods of CR in flies, rodents, monkeys, and humans. In humans and
      nonhuman primates, CR produces most of the physiologic, hematologic, hormonal,
      and biochemical changes it produces in other animals. In primates, CR provides
      protection from type 2 diabetes, cardiovascular and cerebral vascular diseases,
      immunological decline, malignancy, hepatotoxicity, liver fibrosis and failure,
      sarcopenia, inflammation, and DNA damage. It also enhances muscle mitochondrial
      biogenesis, affords neuroprotection; and extends mean and maximum lifespan. CR
      rapidly induces antineoplastic effects in mice. Most claims of lifespan extension
      in rodents by drugs or nutrients are confounded by CR effects. Transcription
      factors and co-activators involved in the regulation of mitochondrial biogenesis
      and energy metabolism, including SirT1, PGC-1alpha, AMPK and TOR may be involved
      in the lifespan effects of CR. Paradoxically, low body weight in middle aged and
      elderly humans is associated with increased mortality. Thus, enhancement of human
      longevity may require pharmaceutical interventions.

PMID- 19853063
TI  - Control of breathing: two types of delays studied in an integrated model of the
      respiratory system.
AB  - We use a recently developed mathematical model that integrates a reduced
      representation of the brainstem respiratory neural controller together with
      peripheral gas exchange and transport to study numerically the dynamic response
      of the respiratory system to several physiological stimuli. We compare between
      the system responses with two major sources of delay: circulatory transport vs.
      neural feedback dynamics, and we show that the dynamics of the neural feedback
      processes dictates the dynamic response to hypoxia and hypercapnia. The source of
      the circulatory delay (blood velocity vs. distance from the lungs to
      chemoreceptors) was found to be important. Our model predicts that periodic
      breathing is associated with the ventilatory "afterdischarge" (slow recovery of
      ventilation) after a brief perturbation of CO(2). We also predict that there
      could be two possible mechanisms for the appearance of periodic breathing and
      that circulatory delay is not a necessary condition for this to occur in certain
      cases.

PMID- 19853064
TI  - Exercise-induced VEGF transcriptional activation in brain, lung and skeletal
      muscle.
AB  - Muscle VEGF expression is upregulated by exercise. Whether this VEGF response is
      regulated by transcription and/or post-transcriptional mechanisms is unknown.
      Hypoxia may be responsible: myocyte P(O2) falls greatly during exercise and VEGF
      is a hypoxia-responsive gene. Whether exercise induces VEGF expression in other
      organs important to acute physical activity is also unknown. To address these
      questions, we created a VEGF-Luciferase reporter mouse and measured VEGF
      transcription, mRNA and protein responses to (a) acute exercise and (b) short
      term hypoxia (FI(O2) = 0.06) in brain (brainstem, cerebellum, cortex, hippocampus
      and striatum), muscle, lung, heart and liver. Exercise increased VEGF
      transcription, mRNA and protein in brain (hippocampus only), lungs and skeletal
      muscles, but not liver or heart. Hypoxia increased VEGF expression only in brain
      (cortex, hippocampus and striatum). New transcription appears to be a major
      exercise-induced regulatory step for increasing VEGF expression in muscle, lung
      and brain. Hippocampal VEGF expression was the only component of the exercise
      response recapitulated by hypoxia equivalent to the Everest summit.

PMID- 19853065
TI  - A comparative analysis of the fluorescence properties of the wild-type and active
      site mutants of the hepatitis C virus autoprotease NS2-3.
AB  - Hepatitis C virus encodes an autoprotease, NS2-3, which is required for
      processing of the viral polyprotein between the non-structural NS2 and NS3
      proteins. This protease activity is vital for the replication and assembly of the
      virus and therefore represents a target for the development of anti-viral drugs.
      The mechanism of this auto-processing reaction is not yet clear but the protease
      activity has been shown to map to the C-terminal region of NS2 and the N-terminal
      serine protease region of NS3. The NS2-3 precursor can be expressed in
      Escherichia coli as inclusion bodies, purified as denatured protein and refolded,
      in the presence of detergents and the divalent metal ion zinc, into an active
      form capable of auto-cleavage. Here, intrinsic tryptophan fluorescence has been
      used to assess refolding in the wild-type protein and specific active site
      mutants. We also investigate the effects on protein folding of alterations to the
      reaction conditions that have been shown to prevent auto-cleavage. Our data
      demonstrate that these active site mutations do not solely affect the cleavage
      activity of the HCV NS2-3 protease but significantly affect the integrity of the
      global protein fold.

PMID- 19853068
TI  - Mechanical modeling of a wrinkled fingertip immersed in water.
AB  - Fingertips often wrinkle after extended exposure to water. The underlying
      mechanics issues, in particular the critical parameters governing the wrinkled
      morphology, are studied by using both finite element simulation and analytical
      modeling. The wrinkling behaviors, characterized by the wrinkle-to-wrinkle
      distance (wavelength), wrinkle depth (amplitude) and critical wrinkling
      stress/strain, are investigated as the geometry and material parameters of the
      fingertip are varied. A simple reduced model is employed to understand the effect
      of finger curvature and skin thickness, whereas a more refined full anatomical
      model provides the basis for analyzing the effect of a multilayered skin
      structure. The simulation results demonstrate that the stiffness of the stratum
      corneum and the dermal layer in the skin has a large effect on the wrinkling
      behavior, which agrees well with the analytical predictions. From the uncovered
      mechanical principles, potential ways for effectively slowing down and
      suppressing skin wrinkles are proposed; among them, increasing the modulus of the
      dermal layer in the skin appears to be the most effective.

PMID- 19853067
TI  - Modified PHBV scaffolds by in situ UV polymerization: structural characteristic,
      mechanical properties and bone mesenchymal stem cell compatibility.
AB  - An ideal scaffold provides an interface for cell adhesion and maintains enough
      biomechanical support during tissue regeneration. Poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV) scaffolds with pore sizes ranging from 100 to 500 microm
      and porosity approximately 90% were prepared by the particulate-leaching method,
      and then modified by the introduction of polyacrylamide (PAM) on the inner
      surface of scaffolds using in situ UV polymerization, with the aim of enhancing
      the biological and mechanical properties of the PHBV scaffolds. The modified PHBV
      scaffolds had interconnected pores with porosity of 75.4-78.6% and pore sizes at
      peak volume from 20 to 50 microm. The compressive load and modulus were up to
      62.45 N and 1.06 MPa, respectively. The water swelling percentage (WSP) of the
      modified PHBV scaffolds increased notably compared with that of the PHBV
      scaffolds, with the maximum WSP at 537%. Sheep bone mesenchymal stem cells (BMSC)
      were cultured on the PHBV and modified PHBV. The hydrophilic PAM chains did not
      influence BMSC viability or proliferation index, but the initial cell adhesion at
      1h of culture was enhanced significantly. Framing PHBV scaffold along with gel
      like PAM chains inside is a novel model of inner surface modification for PHBV
      scaffolds, which shows potential in tissue engineering applications.

PMID- 19853066
TI  - Biodegradable fibrous scaffolds with diverse properties by electrospinning
      candidates from a combinatorial macromer library.
AB  - The properties of electrospun fibrous scaffolds, including degradation, mechanics
      and cellular interactions, are important for their use in tissue engineering
      applications. Although some diversity has been obtained previously in fibrous
      scaffolds, optimization of scaffold properties relies on iterative techniques in
      both polymer synthesis and processing. Here, we electrospun candidates from a
      combinatorial library of biodegradable and photopolymerizable poly(beta-amino
      ester)s (PBAEs) to show that the diversity in properties found in this library is
      retained when processed into fibrous scaffolds. Specifically, three PBAE
      macromers were electrospun into scaffolds and possessed similar initial
      mechanical properties, but exhibited mass loss ranging from rapid (complete
      degradation within approximately 2 weeks) to moderate (complete degradation
      within approximately 3 months) to slow (only partial degradation after 3 months).
      These trends in mechanics and degradation mimicked what was previously observed
      in the bulk polymers. Although cellular adhesion was dependent on the polymer
      composition in films, adhesion to scaffolds that were electrospun with gelatin
      was similar on all formulations and controls. To further illustrate the diverse
      properties that are attainable in these systems, the fastest and slowest
      degrading polymers were electrospun together into one scaffold, but as distinct
      fiber populations. This dual-polymer scaffold exhibited behavior in mass loss and
      mechanics with time that fell between the single-polymer scaffolds. In general,
      this work indicates that combinatorial libraries may be an important source of
      information and specific polymer compositions for the fabrication of electrospun
      fibrous scaffolds with tunable properties.

PMID- 19853070
TI  - Muscle and bone follow similar temporal patterns of recovery from muscle-induced
      disuse due to botulinum toxin injection.
AB  - If muscle force is a primary source for triggering bone adaptation, with disuse
      and reloading, bone changes should follow muscle changes. We examined the timing
      and magnitude of changes in muscle cross-sectional area (MCSA) and bone
      architecture in response to muscle inactivity following botulinum toxin (BTX)
      injection. We hypothesized that MCSA would return to baseline levels sooner than
      bone properties following BTX injection. Female BALB mice (15 weeks old) were
      injected with 20 muL of BTX (1 U/100 g body mass, n=18) or saline (SAL, n=18)
      into the posterior calf musculature of one limb. The contralateral limb (CON)
      served as an internal control. MCSA and bone properties were assessed at
      baseline, 2, 4, 8, 12, and 16 weeks post-injection using in vivo micro-CT at the
      tibia proximal metaphysis (bone only) and diaphysis. Muscles were dissected and
      weighed after sacrifice. Significant GroupxLegxTime interactions indicated that
      the maximal decrease in MCSA (56%), proximal metaphyseal BV/TV (38%) and proximal
      diaphyseal Ct.Ar (7%) occurred 4 weeks after injection. There was no delay prior
      to bone recovery as both muscle and bone properties began to recover after this
      time, but MCSA and BV/TV remained 15% and 20% lower, respectively, in the BTX
      injected leg than the BTX-CON leg 16 weeks post-injection. Gastrocnemius mass
      (primarily fast-twitch) was 14% lower in the BTX-injected leg than the SAL
      injected leg, while soleus mass (primarily slow-twitch) was 15% greater in the
      BTX group than the SAL group. Our finding that muscle size and bone began to
      recover at similar times after BTX injection was unexpected. This suggested that
      partial weight-bearing and/or return of slow-twitch muscle activity in the BTX
      leg may have been sufficient to stimulate bone recovery. Alternatively, muscle
      function may have recovered sooner than MCSA. Our results indicated that muscle
      cross-sectional area, while important, may not be the primary factor associated
      with bone loss and recovery when muscle atrophy is induced through BTX injection.
      To understand the nature of the interaction between muscle and bone, future work
      should focus on the functional recovery of individual muscles in relation to
      bone.

PMID- 19853069
TI  - Reduced size-independent mechanical properties of cortical bone in high-fat diet
      induced obesity.
AB  - Overweight and obesity are rapidly expanding health problems in children and
      adolescents. Obesity is associated with greater bone mineral content that might
      be expected to protect against fracture, which has been observed in adults.
      Paradoxically, however, the incidence of bone fractures has been found to
      increase in overweight and obese children and adolescents. Prior studies have
      shown some reduced mechanical properties as a result of high-fat diet (HFD) but
      do not fully address size-independent measures of mechanical properties, which
      are important to understand material behavior. To clarify the effects of HFD on
      the mechanical properties and microstructure of bone, femora from C57BL/6 mice
      fed either a HFD or standard laboratory chow (Chow) were evaluated for structural
      changes and tested for bending strength, bending stiffness and fracture
      toughness. Here, we find that in young, obese, high-fat fed mice, all geometric
      parameters of the femoral bone, except length, are increased, but strength,
      bending stiffness, and fracture toughness are all reduced. This increased bone
      size and reduced size-independent mechanical properties suggests that obesity
      leads to a general reduction in bone quality despite an increase in bone
      quantity; yield and maximum loads, however, remained unchanged, suggesting
      compensatory mechanisms. We conclude that diet-induced obesity increases bone
      size and reduces size-independent mechanical properties of cortical bone in mice.
      This study indicates that bone quantity and bone quality play important
      compensatory roles in determining fracture risk.

PMID- 19853071
TI  - Insulin-like growth factor-1 is associated with bone formation markers, PTH and
      bone mineral density in healthy premenopausal women.
AB  - Bone turnover markers (BTM) progressively decrease in young adult women. This
      might be linked to changes in insulin-like growth factor-1 (IGF-I). Four serum
      BTMs [serum C-telopeptide of type 1 collagen (CTX), osteocalcin (OC), N-terminal
      propeptide of type 1 procollagen (P1NP), and bone alkaline phosphatase (bone
      AP)], serum calcium (sCa), phosphate (sPO(4)), magnesium, 25-hydroxyvitamin D
      [25(OH)D], intact parathyroid hormone (PTH) and IGF-I were measured in 531 young
      healthy premenopausal women aged 20-50 years participating in the BONTURNO study.
      In all subjects bone mineral density (BMD) was measured at the spine and at the
      hip by dual-energy X-ray densitometry. Hip BMD, IGF-I, the four BTMs, sCa and
      sPO(4) progressively decreased with advancing age and this was associated with
      proportional increases in PTH. IGF-I levels were significantly and positively
      correlated with sCa, sPO(4), CTX, OC, P1NP, bone AP, spine BMD, femoral neck BMD
      and total hip BMD and negatively with age, BMI and serum PTH. When the IGF-I
      levels were adjusted for age and BMI, the only correlations maintaining a
      statistical significance were those with serum PTH, P1NP and bone AP. These
      associations were weak and IGF-I accounted for a only a small proportion of the
      BTM variance. The mean, age-adjusted IGF-I values were significantly higher in
      women practicing physical exercises for more then 60 min per week than in
      sedentary women. In conclusion, in this study we provide evidence of an
      association between the age-related decline in IGF-I with the progressive
      decrease in bone formation markers in premenopausal women.

PMID- 19853073
TI  - National influenza surveillance in Vietnam, 2006-2007.
AB  - In 2006, national influenza surveillance was implemented in Vietnam.
      Epidemiologic and demographic data and a throat swab for influenza testing were
      collected from a subset of outpatients with influenza-like illness (ILI). During
      January 1, 2006 through December 31, 2007, of 184,521 ILI cases identified at
      surveillance sites, 11,082 were tested and 2112 (19%) were positive for influenza
      by reverse transcription polymerase chain reaction. Influenza viruses were
      detected year-round, and similar peaks in influenza activity were observed in all
      surveillance regions, coinciding with cooler and rainy periods. Studies are
      needed to ascertain the disease burden and impact of influenza in Vietnam.

PMID- 19853072
TI  - HO-1 expression increases mesenchymal stem cell-derived osteoblasts but decreases
      adipocyte lineage.
AB  - Human bone marrow mesenchymal stem cells (MSC) are pleiotropic cells that
      differentiate to either adipocytes or osteoblasts as a result of cross-talk by
      specific signaling pathways including heme oxygenase (HO)-1/-2 expression. We
      examined the effect of inducers of HO-1 expression and inhibitors of HO activity
      on MSC differentiation to the osteoblast and adipocyte lineage. HO-1 expression
      is increased during osteoblast stem cell development but remains elevated at 25
      days. The increase in HO-1 levels precedes an increase in alkaline phosphatase
      (AP) activity and an increase in BMP, osteonectin and RUNX-2 mRNA. Induction of
      HO-1 by osteogenic growth peptide (OGP) was associated with an increase in BMP-2
      and osteonectin. Exposure of MSC to high glucose levels decreased osteocalcin and
      osteogenic protein expression, which was reversed by upregulation of the OGP
      mediated increase in HO-1 expression. The glucose-mediated decrease in HO-1
      resulted in decreased levels of pAMPK, pAKT and the eNOS signaling pathway and
      was reversed by OGP. In contrast, MSC-derived adipocytes were increased by
      glucose. HO-1 siRNA decreased HO-1 expression but increased adipocyte stem cell
      differentiation and the adipogenesis marker, PPARgamma. Thus, upregulation of HO
      1 expression shifts the balance of MSC differentiation in favor of the osteoblast
      lineage. In contrast, a decrease in HO-1 or exposure to glucose drives the MSC
      towards adipogenesis. Thus, targeting HO-1 expression is a portal to increased
      osteoblast stem cell differentiation and to the attenuation of osteoporosis by
      the promotion of bone formation.

PMID- 19853074
TI  - Ovine atadenovirus, a novel and highly immunogenic vector in prime-boost studies
      of a candidate HIV-1 vaccine.
AB  - Ovine adenovirus type 7 (OAdV) is the prototype member of the genus Atadenovirus.
      No immunity to the virus has so far been detected in human sera. We describe the
      construction and evaluation of a candidate HIV-1 vaccine based on OAdV and its
      utilisation alone and in combination with plasmid-, human adenovirus type 5
      (HAdV5; a Mastadenovirus)-, and modified vaccinia Ankara (MVA)-vectored vaccines.
      All vectors expressed HIVA, an immunogen consisting of HIV-1 clade A consensus
      Gag-derived protein coupled to a T cell polyepitope. OAdV.HIVA was genetically
      stable, grew well and expressed high levels of protein from the Rous sarcoma
      virus promoter. OAdV.HIVA was highly immunogenic in mice and efficiently primed
      and boosted HIV-1-specific T cell responses together with heterologous HIVA
      expressing vectors. There were significant differences between OAdV and HAdV5
      vectors in priming of naive CD8(+) T cell responses to HIVA and in the
      persistence of MHC class I-restricted epitope presentation in the local draining
      lymph nodes. OAdV.HIVA primed T cells more rapidly but was less persistent than
      AdV5.HIVA and thus induced a qualitatively distinct T cell response.
      Nevertheless, both vectors primed a response in mice that reduced viral titres in
      a surrogate challenge model by three to four orders of magnitude. Thus, OAdV is a
      novel, underexplored vaccine vector with potential for further development for
      HIV-1 and other vaccines. The data are discussed in the context of the latest HIV
      1 vaccine developments.

PMID- 19853075
TI  - Left ventricular assist devices: psychosocial challenges in the elderly.
AB  - As the baby boom generation ages, the number of people with heart failure is
      expected to rise exponentially. A rapid increase in the demand for heart
      transplants will result in an increased use of left ventricular assist devices.
      This case illustrates the challenges facing transplant teams in evaluating
      elderly heart failure patients as candidates for assist devices. The critical
      elements of a psychosocial assessment are described.

PMID- 19853076
TI  - Percutaneous implantation of CoreValve aortic prostheses in patients with a
      mechanical mitral valve.
AB  - Concerns exist in the field of transcatheter aortic valve implantation regarding
      the treatment of patients with mechanical mitral valve for possible interference
      between the percutaneous aortic valve and the mechanical mitral prosthesis. We
      report our experience with percutaneous aortic valve implantation in 4 patients
      with severe aortic stenosis, previously operated on for mitral valve replacement
      with a mechanical prosthesis. All patients underwent uneventful percutaneous
      retrograde CoreValve implantation (CoreValve Inc, Irvine, CA). No deformation of
      the nitinol tubing of the prostheses (ie, neither distortion nor malfunction of
      the mechanical valve in the mitral position) occurred in any of the patients. All
      patients are alive and asymptomatic at a mean follow-up of 171 days.

PMID- 19853077
TI  - Cardiac tamponade: chylopericardium presenting 2 weeks after mechanical aortic
      valve replacement through a median sternotomy.
AB  - Chylopericardium is a rare disorder that can be secondary to thoracic duct
      injury. Consequences include nutritional, metabolic, and immunologic
      abnormalities, as well as cardiac complications, such as pericarditis and cardiac
      tamponade. We present a case of chylopericardium presenting as cardiac tamponade
      after a median sternotomy for mechanical aortic valve replacement.

PMID- 19853078
TI  - Extracorporeal membrane oxygenation bridging to living-donor lobar lung
      transplantation.
AB  - A 21-year-old man with pulmonary fibrosis and a 27-year-old woman with idiopathic
      pulmonary hypertension, who were in pulmonary hypertensive crisis, were
      successfully treated by using venoarterial extracorporeal membrane oxygenation,
      followed by living-donor lobar lung transplantation. In both of the patients,
      bridging time of extracorporeal membrane oxygenation to lung transplantation was
      2 days, and both could be weaned from cardiopulmonary support immediately after
      transplantation in the operating room. No major complications were seen,
      including primary graft dysfunction. The cardiopulmonary functions of these
      patients markedly improved after living-donor lobar lung transplantation.

PMID- 19853079
TI  - Uncommon etiology of an anterior chest wall mass.
AB  - A rare but important constellation of musculoskeletal and cutaneous symptoms,
      including synovitis, acne, pustulosis, hyperostosis, and osteitis, has recently
      been designated the SAPHO syndrome. The exact etiology is unknown, although
      various infectious agents have been proposed. The most common site of
      osteoarticular involvement is the sternoclavicular joint, and therefore,
      recognition of this syndrome and appropriate workup and management is crucial in
      the differential diagnosis of an anterior chest wall mass.

PMID- 19853080
TI  - Surgeon specialty is associated with better outcomes: the facts speak for
      themselves.

PMID- 19853081
TI  - Microcirculatory alterations in cardiac surgery: effects of cardiopulmonary
      bypass and anesthesia.
AB  - BACKGROUND: Heterogeneity in microvascular perfusion is associated with impaired
      tissue oxygenation. We hypothesized that cardiac surgery with or without
      cardiopulmonary bypass (CPB) could induce microvascular alterations. METHODS: We
      used an orthogonal polarization spectral imaging technique to evaluate the
      sublingual microcirculation in patients undergoing cardiac surgery with (n = 9)
      or without (n = 6) CPB. We also included, as a control group, 7 patients
      undergoing thyroidectomy with the same anesthetic procedure. Hemodynamic and
      microcirculatory variables were obtained the day before surgery, after induction
      of anesthesia, during CPB, on admission to the intensive care unit or the
      recovery room, and 6 and 24 hours after the end of the surgical procedure. Data
      are presented as median (25th to 75th percentile). RESULTS: No differences in
      hemodynamic variables were observed between the two cardiac surgery groups. The
      proportion of perfused vessels was similar in all three groups at baseline (89%
      [87% to 90%]), and decreased similarly after induction of anesthesia to 71% (69%
      to 74%). It decreased further during CPB to 53% (50% to 56%). On admission to the
      intensive care unit or recovery room, alterations were more severe in CPB than in
      off-pump patients (60% [59% to 62%] versus 64% [61% to 65%]; p = 0.03), whereas
      they had already normalized in thyroidectomy patients (89% [86% to 90%]; p =
      0.0005 versus cardiac surgery). In both cardiac surgery groups these
      microcirculatory alterations decreased with time, but persisted at 24 hours. The
      severity of microvascular alterations correlated with peak lactate levels after
      cardiac surgery (y = 11.5 - 0.15x; r(2) = 0.65; p < 0.05). CONCLUSIONS:
      Microcirculatory alterations are observed in cardiac surgery patients whether or
      not CPB is used. Anesthesia contributes to these alterations, but its effects are
      transient.

PMID- 19853082
TI  - Choice of conduit for the right coronary system: 8-year analysis of Radial Artery
      Patency and Clinical Outcomes trial.
AB  - BACKGROUND: Previous reports have supported the use of bilateral internal
      thoracic arteries to revascularize the left coronary circulation. If this becomes
      standardized practice, the optimal conduit for the right coronary system remains
      to be established. Our objective is to compare the performance of the radial
      artery versus the saphenous vein when used to graft the right coronary artery or
      its branches during an 8-year period after primary coronary artery bypass graft
      surgery. METHODS: The Radial Artery Patency and Clinical Outcomes study is a
      randomized controlled trial comparing radial artery, saphenous vein, and free
      right internal thoracic artery. Of the 621 patients enrolled in the study, 465
      patients received a graft to the right coronary artery or its branches. The
      retrospectively compiled database was used to establish patency rates and
      clinical events among these patients. RESULTS: Absolute graft patency rates were
      as follows: radial artery, 86.9% of 68 (95% confidence interval, 76.6% to 93.1%);
      and saphenous vein, 81.2% of 197 (95% confidence interval, 75.1% to 86.1%).
      Noninferiority tests show that absolute radial patency to saphenous patency is at
      least 0.9526 (p = 0.025). Kaplan-Meier estimates of angiographic outcomes show no
      significant difference (log rank p = 0.22). Cardiac events in the right coronary
      territory occurred in the radial artery group (1.79%) versus the saphenous vein
      group (4.93%; p = 0.26). Overall mortality was 8.03% in the radial artery group
      versus 12.5% in the saphenous vein group (p = 0.23). CONCLUSIONS: The radial
      artery patency is at least comparable to that of the saphenous vein when grafted
      to the right coronary artery or its branches. The paucity of clinical events in
      both grafts is notable. Selection of best conduit may therefore be made according
      to other factors.

PMID- 19853083
TI  - Transfusion and pulmonary morbidity after cardiac surgery.
AB  - BACKGROUND: True lung injury is among the leading causes of transfusion-related
      mortality. Pulmonary morbidity after cardiac surgery has been related to damaging
      effects of cardiopulmonary bypass and transfusion, but is confounded by cardiac
      related events that may not reflect true lung injury. Thus, cardiac surgery poses
      unique challenges to criteria-specific diagnosis of transfusion-related acute
      lung injury (TRALI). Our objective was to determine the prevalence of pulmonary
      morbidity related to transfusion and whether TRALI consensus-criteria are
      applicable to cardiac surgery. METHODS: A total of 16,847 patients underwent on
      pump, coronary artery bypass grafting (CABG), valve, or CABG-valve surgery from
      September 1998 to February 1, 2006. We performed four propensity-score-matching
      analyses with logistic regression on probability of receiving a transfusion:
      total hospital red blood cell (RBC) and fresh frozen plasma (FFP) transfusion and
      intraoperative RBC and FFP transfusion. Outcomes included traditional cardiac
      surgery-defined pulmonary morbidity and ratio of arterial partial pressure of
      oxygen to fractional inspired oxygen concentration (PaO(2)/FiO(2)), a criterion
      for TRALI. RESULTS: Patients receiving RBC transfusion had more risk-adjusted
      pulmonary complications: respiratory distress 4.8% vs 1.5%, p < 0.001;
      respiratory failure 2.2% vs 0.39%, p < 0.0001; longer intubation times, 9.9 hours
      vs 7.5 hours, p < 0.0001; acute respiratory distress syndrome, 0.64% vs 0.21%, p
      = 0.015; and reintubation, 5.6% vs 1.3%, p < 0.0001. The FFP was similarly
      related to more pulmonary complications after surgery. By TRALI criteria, the
      majority manifested "lung injury" (PaO(2)/FiO(2) ratio < 300) but unrelated to
      transfusion (65% vs 64%). CONCLUSIONS: Transfusion is associated with many
      measures of postoperative pulmonary morbidity. Yet the PaO(2)/FiO(2) ratio as
      important criterion of TRALI is unrelated to transfusion. Thus, due to the nature
      of cardiac surgery, application of consensus guided diagnosis of TRALI is
      problematic.

PMID- 19853084
TI  - Improved myocardial perfusion and thickening after off-pump revascularization: 5
      year follow-up.
AB  - BACKGROUND: Late improvements in myocardial perfusion and thickening after off
      pump revascularization were evaluated during a 5-year follow-up by myocardial
      single photon emission computed tomography. METHODS: Between 2001 and 2003, 68
      patients who underwent off-pump coronary artery bypass grafting using bilateral
      internal thoracic artery Y-composite (group Y, n = 41) or in situ (group I, n =
      27) grafts for revascularization of the left coronary artery territory were
      enrolled. Myocardial single photon emission computed tomography was performed
      preoperatively and at 3 months, 1 year, and 5 years postoperatively. A 20-segment
      model was adopted. As an indicator of ischemic myocardium, the reversibility
      score was defined as a measure of rest minus stress perfusion values. A total of
      374 segments that showed a reversibility score of > or = 7 preoperatively were
      included. Z values for thickening were calculated as observed values minus
      reference values divided by the reference standard deviation. Mixed-model
      analysis was used to compare the two groups with respect to the time sequences of
      myocardial reversibility scores and Z values. RESULTS: Postoperative
      reversibility scores improved significantly at 3 months (p < 0.001) and further
      at 5 years (p = 0.030). Postoperative Z values improved significantly at 3 months
      (p < 0.001), between 1 year and 5 years (p = 0.006), and further at 5 years (p =
      0.004). In the mixed models, there were no significant differences in
      reversibility scores and Z values between groups Y and I at any point.
      CONCLUSIONS: Reversibility scores and thickening gradually improved during 5
      years after off-pump revascularization using bilateral internal thoracic
      arteries. No significant differences were observed between Y-composite and
      bilateral in situ grafts in terms of reversibility score and thickening
      improvement at 5 years postoperatively.

PMID- 19853085
TI  - Plasma amyloid beta42 and amyloid beta40 levels are associated with early
      cognitive dysfunction after cardiac surgery.
AB  - BACKGROUND: Decreased cognitive function associated with coronary artery bypass
      graft surgery is common. These deficits may be similar to the cognitive
      dysfunction seen in the spectrum of mild cognitive impairment to Alzheimer's
      disease, which are believed to result from the accumulation of amyloid beta
      (Abeta) peptide in the brain. We measured cognition both before and after
      coronary artery bypass graft surgery and assayed Abeta levels to investigate
      whether the cognitive dysfunction of cardiac surgery was associated with Abeta
      levels. METHODS: The plasma of 332 patients, who had undergone neuropsychological
      testing before and 3 and 12 months after coronary artery bypass graft surgery,
      was analyzed for Abeta(42) and Abeta(40). Patients were classified as having
      preexisting cognitive impairment if cognitive function was decreased in two or
      more tests compared with a healthy control group, and postoperative cognitive
      dysfunction was defined as a decline in two or more tests compared with the group
      mean baseline score. RESULTS: Preexisting cognitive impairment was present in 117
      patients (35.2%), and postoperative cognitive dysfunction was present in 40 (12%)
      at 3 months and 41 (13%) at 12 months after surgery. Both plasma Abeta(42) and
      Abeta(40) levels assessed before the surgery were significantly lower in patients
      who later had postoperative cognitive dysfunction at 3 months. CONCLUSIONS:
      Decreased preoperative plasma levels of Abeta(42) and Abeta(40) in patients who
      exhibit postoperative cognitive dysfunction at 3 months suggest that
      postoperative cognitive dysfunction at this time may share a common mechanism
      with mild cognitive impairment and Alzheimer's disease. This process may be
      exacerbated by anesthesia.

PMID- 19853086
TI  - Invited commentary.

PMID- 19853087
TI  - A three-group model to predict mortality in emergent coronary artery bypass graft
      surgery.
AB  - BACKGROUND: Emergent coronary artery bypass graft surgery (CABG) for acute
      myocardial infarction is associated with an increased operative risk. For
      estimation of mortality risk, the European System for Cardiac Operative Risk
      Evaluation (EuroSCORE) is appropriate up to a medium risk score (<6 points). To
      predict mortality risk more accurately in cases of higher EuroSCORE, additional
      cardiac data can be helpful. METHODS: Over a 3-year period, patient data
      including acute myocardial infarction and emergent CABG were retrospectively
      reviewed. Univariate and multivariate analysis for in-hospital mortality was
      performed. The EuroSCORE analysis and follow-up was investigated. RESULTS:
      Overall in-hospital mortality was 18.3%. Preoperative cardiac related predictors
      for in-hospital mortality were cardiogenic shock (p < 0.001), very poor left
      ventricular function (p = 0.001), and ST-segment elevation (p = 0.012). In
      multivariate regression analysis, age, cardiogenic shock, and pulmonary
      hypertension were independent preoperative risk factors. According to the
      EuroSCORE, we could define three statistically different groups: intermediate
      risk, high-risk, and very high risk, with an observed mortality of 3.3%, 20.0%,
      and 63.2%, respectively. The EuroSCORE correlates with but overestimates the
      mortality risk. In subgroup analysis, the creatine kinase-myocardial band/hour
      ratio for the intermediate-risk group and ST-segment elevation for the high-risk
      group were additional cardiac risk factors. CONCLUSIONS: Patients with an acute
      myocardial infarction and emergency aortocoronary CABG have an elevated operative
      risk. Logistic EuroSCORE overestimates the mortality rate. Three different risk
      groups can be defined, in which creatine kinase-MB/h-ratio and ST-segment
      elevation can more accurately predict operative risk.

PMID- 19853088
TI  - Efficacy of aggressive lipid controlling therapy for preventing saphenous vein
      graft disease.
AB  - BACKGROUND: We assessed the efficacy of aggressive lipid controlling therapy
      (ALCT), which maintains low-density lipoprotein cholesterol (LDL-C) below to 80
      mg/dL and LDL/high-density lipoprotein cholesterol (HDL-C) ratio less than 1.5
      for preventing postcoronary bypass (CABG) saphenous vein graft (SVG) diseases by
      using intracoronary angioscopy. METHODS: Twenty-one patients after CABG were
      divided into two groups: group I consisted of 10 patients whose serum LDL-C level
      and LDL/HDL could be controlled less than 80 mg/dL and 1.5, respectively, by
      rosuvastatin for about one year; group II consisted of 11 patients whose LDL-C
      level and LDL/HDL have been higher than 100 mg/dL and 2.5, respectively,
      regardless of having medication of pravastatin. Twenty-seven SVGs were assessed
      by intravascular ultrasound (IVUS) and angioscopy on postoperative 12 to 16
      months. RESULTS: The serum LDL-C level (I: 64.1 vs II: 130.2 mg/dL) and LDL/HDL
      (I: 1.36 vs II: 2.64), and high sensitive C-reactive protein (I: 0.045 +/- 0.100
      vs II: 0.116 +/- 0.020 mg/dL) were significantly lower in group I. In group II,
      IVUS detected eccentric plaques in 11 (78.6%) of 14 SVGs. Furthermore the
      angioscope showed yellow plaque in all 14 SVGs (100%) and 11 (78.6%) of them had
      thrombi. On the other hand, in group I, all 13 SVGs had no eccentric, yellow
      plaques or thrombi and the intima was entirely clear white. CONCLUSIONS:
      Prophylactic treatment for yellow plaque and thrombus formation are extremely
      important in the development of early and late SVG disease. Aggressive lipid
      controlling therapy is quite attractive to avoid post CABG SVG disease and may be
      effective to maintain the long-term graft patency.

PMID- 19853089
TI  - Randomized prospective study comparing conventional subcuticular skin closure
      with Dermabond skin glue after saphenous vein harvesting.
AB  - BACKGROUND: Dermabond (Ethicon UK, Edinburgh, United Kingdom) is a topical skin
      adhesive used for surgical wound closure, with purported advantages over
      conventional sutures on cosmetic outcomes, cost benefits, and operative times.
      This study compared results of skin closure using Dermabond and subcuticular
      sutures after coronary artery bypass grafting (CABG). METHODS: The study
      prospectively enrolled and randomized 106 patients who underwent CABG. The groups
      received closure with Dermabond skin glue or subcuticular sutures (n = 53 each)
      after saphenous vein harvesting using the bridging technique. Wound closure time
      for the two methods was recorded. Cosmetic appearance was assessed using the
      Hollander, the Vancouver, and the visual analog scale. Patient satisfaction was
      recorded before discharge and at week 6. RESULTS: There were no significant
      differences in the total operative time between the two groups (p = 0.43).
      Closure time was significantly shorter in the Dermabond group (p = 0.017).
      Patients in the Dermabond group also reported superior cosmetic outcome at weeks
      1 (p < 0.001) and 6 (p = 0.001) and improved patient satisfaction (p < 0.001).
      CONCLUSIONS: Dermabond has demonstrated superiority over traditional subcuticular
      skin sutures in terms of closure time, cosmetic appearance, and patient
      satisfaction. This technique provides a novel method of wound closure after CABG.

PMID- 19853090
TI  - Invited commentary.

PMID- 19853091
TI  - Diabetes mellitus and long-term outcome in heart failure patients after surgical
      ventricular restoration.
AB  - BACKGROUND: This study aimed to identify the impact of diabetes mellitus and
      related comorbidities on long-term survival of heart failure patients who had
      undergone surgical ventricular restoration. Surgical ventricular restoration is
      an optional therapeutic strategy for patients with ischemic dilated
      cardiomyopathy. Reported prognostic predictors for late morbidity and mortality
      are predominantly related to cardiac conditions, whereas the prognostic impact of
      comorbidities still needs to be defined. METHODS: A total of 329 patients (234
      nondiabetic and 95 diabetic) who survived the surgical ventricular restoration
      operation were admitted to this study. Cardiac mortality follow-up data were
      collected. Actuarial survival curves were calculated for the two groups;
      differences between groups and the impact of other comorbidities were established
      using a log-rank test and a Cox regression analysis. RESULTS: The mean follow-up
      time was 44 months. Diabetic patients had a significantly worse survival rate: at
      5 years, their survival rate was 81%, versus 89% for nondiabetic patients (p =
      0.019). Other comorbidities significantly associated with the survival rate were
      chronic renal failure, New York Heart Association class, and liver dysfunction.
      Diabetic patients without comorbidities had a survival rate similar to that of
      nondiabetic patients. Diabetic patients with at least one comorbidity had a
      significantly worse outcome. Diabetic patients with chronic renal failure had a 5
      year survival rate of 40%, versus 85% for nondiabetic patients (p = 0.002).
      CONCLUSIONS: Noncomplicated diabetes has no negative impact on long-term survival
      after surgical ventricular restoration. Conversely, complicated diabetes, namely
      the presence of chronic renal failure, carries a long-term cardiac mortality risk
      that is four times higher than the risk for nondiabetic patients.

PMID- 19853092
TI  - Impact of left ventricular assist device bridging on posttransplant outcomes.
AB  - BACKGROUND: Bridge to heart transplantation with a left ventricular assist device
      (LVAD) can be a promising therapy for patients who are not effectively stabilized
      with conservative measures. However, referral for LVAD therapy may be limited
      secondary to reports of poor outcomes when mechanical circulatory support is
      required before transplantation. METHODS: A retrospective review was undertaken
      to evaluate outcomes in United Network of Organ Sharing (UNOS) status 1 heart
      transplant recipients who were bridged to transplant with an implantable LVAD or
      with intravenous inotropes only from 1994 to 2007. Preoperative characteristics,
      posttransplant survival, and postoperative complications were compared between 86
      patients with an implantable LVAD and 173 patients bridged with intravenous
      inotropes only. RESULTS: The patients had similar baseline characteristics and
      pretransplant hemodynamics. Hemodynamics in the LVAD group, as measured by
      cardiac index, pulmonary vascular resistance, central venous pressure, and
      pulmonary capillary wedge pressure, significantly improved during mechanical
      support. Short-term and long-term posttransplant survival and the incidence of
      posttransplant infectious complications and rejection episodes during the first
      year was similar. The incidence of posttransplant renal dysfunction was higher in
      patients bridged with inotropes. CONCLUSIONS: Patients bridged to transplant with
      a LVAD represent a subset of UNOS status 1 patients who deteriorated on
      intravenous inotropic therapy. Bridging to heart transplantation with an
      implantable LVAD provides comparable outcomes to similar status 1 patients who
      were stabilized on inotropic infusions only. In contrast with International
      Society of Heart and Lung Transplantation data, no increase in posttransplant
      morbidity or mortality occurred in LVAD-bridged patients.

PMID- 19853093
TI  - Role of a percutaneous ventricular assist device in decision making for a cardiac
      transplant program.
AB  - BACKGROUND: The role of a percutaneous ventricular assist device (VAD) for left
      heart support in the management of patients in cardiogenic shock is not well
      defined. METHODS: All patients who received LV support using the percutaneous
      TandemHeart (percTH) ventricular support device (Cardiac Assist, Pittsburgh, PA)
      were retrospectively reviewed. Indications for insertion included bridge to
      decision (BTD) or "salvage" and bridge to transplant (BTT). RESULTS: Between
      April 2005 and December 2008, 22 percTH devices were successfully implanted in
      patients (13 men) with isolated left heart failure. Mean duration of support was
      6.8 +/- 9.4 days (median, 4; maximum, 45 days). Of patients requiring percTH
      support for at least 3 days, mean pump flows were 3.77 +/- 1.10, 4.22 +/- 0.69,
      and 4.04 +/- 0.41 L/min on at days 1, 2, and 3. Mean serum aspartate
      aminotransferase levels were 455 +/- 994 mg/dL before percTH, 551 +/- 1046 mg/dL
      at day 1, and 231 +/- 225 mg/dL at day 3 after percTH. No mechanical device
      failure, device-related infections, or cerebrovascular accidents occurred. Ten of
      11 BTT patients were successfully bridged. Support was withdrawn in 7 of 11 BTD
      patients. The percTHs were successfully explanted in 4 BTD patients: 1 as
      recovery, 1 direct to transplant, and 2 to VAD. CONCLUSIONS: The percTH was
      reliable, with no mechanical device failures and minimal associated adverse
      events. We support the use of the percTH in the BTD mode, allowing time for a
      more complete evaluation of neurologic and end-organ status without the added
      expense and morbidity of a long-term VAD.

PMID- 19853094
TI  - Invited commentary.

PMID- 19853095
TI  - Transcatheter aortic valve implantation in patients with very high risk for
      conventional aortic valve replacement.
AB  - BACKGROUND: We sought to determine whether transcatheter aortic valve
      implantation is a reasonable treatment option in patients with a very or
      extremely high risk for conventional aortic valve replacement, presenting with a
      logistic EuroSCORE greater than 30% or a Society of Thoracic Surgeons score
      greater than 15%. METHODS: Between May 2005 and November 2008, 39 of 85
      transcatheter aortic valve implantation patients with a very high risk for aortic
      valve replacement underwent either transfemoral (n = 15) or transapical (n = 24)
      transcatheter aortic valve implantation with a mean estimated logistic EuroSCORE
      of 44.2% +/- 12.6% (mean +/- standard deviation) and a Society of Thoracic
      Surgeons score of 17.9% +/- 6.1%. Transcatheter aortic valve implantation was
      performed in a hybrid operative theater using the Cribier-Edwards or Edwards
      SAPIEN prosthesis. RESULTS: Valve implantation was successful in 97% of the
      patients. Operative mortality was 2.6%, and mortality at 30 days was 17.9%. After
      valve implantation, hemodynamic improvement was assessed by decreased mean
      pressure gradient (p < 0.001) and increased aortic valve area (p < 0.001),
      accompanied by improved New York Heart Association functional status (p < 0.01).
      Actuarial survival was 74.4% at 3 months, 74.4% at 6 months, and 64.1% at 12
      months of follow-up. Echocardiography revealed aortic regurgitation in 58% of the
      patients during hospital stay, 43% at 6 months of follow-up, and 40% at 12 months
      of follow-up, but no structural valve deterioration could be observed during the
      complete follow-up period. CONCLUSIONS: Transcatheter aortic valve implantation
      in patients with severe aortic stenosis and a very high risk for aortic valve
      replacement is feasible and may be a reasonable treatment option in these
      patients.

PMID- 19853096
TI  - Invited commentary.

PMID- 19853097
TI  - Mechanical strain and the aortic valve: influence on fibroblasts, extracellular
      matrix, and potential stenosis.
AB  - BACKGROUND: Mechanical strain may affect aortic valve cusp, leading to an altered
      extracellular matrix ultrastructure and eventually aortic stenosis. The aim of
      this study was to evaluate the affect of these potential relationships on human
      tissue. METHODS: Extracellular matrix protein disposition was analyzed on human
      aortic valve cusp retrieved from 31 patients during routine aortic valve
      replacement surgery. Samples were immediately fixed in 2-hydroxyethyl
      methacrylate. Immunohistology and Western blot analysis were used to quantify
      decorin, tenascin-C, biglycan, alkaline-phosphatase, osteocalcin, and osteopontin
      content. Fibroblast function was analyzed on interstitial cells derived from
      aortic valve cups from patients undergoing aortic valve replacement. Cells were
      grown to confluency in modified Eagle's medium supplemented with 10% fetal calf
      serum under sterile conditions. Thereafter, mechanical strain was applied for 72
      hours and 60 cycles per minute. Elongation of as much as 10% in comparison with
      no elongation (control group) was applied. All results were correlated to
      hemodynamic variables. RESULTS: Decorin and biglycan were mostly located at the
      inflow aspects of the cusp, tenascin-C in the central layer, and osteopontin,
      osteocalcin, and alkaline phosphatase were concentrated near the cell populations
      surrounding calcified areas. The intensity of this protein expression was
      significantly related to the pressure gradient. Expression levels were twice to
      five times higher than normal in patients with a preoperative pressure gradient
      of more than 100 mm Hg. On fibroblasts subjected to mechanical strain, a similar
      significant increase in the expression for decorin, biglycan, alkaline
      phosphatase, tenascin-C, osteocalcin, and osteopontin was found by
      immunohistology. Western blot analysis confirmed significantly enhanced
      expressions of two and eight times the normal levels. CONCLUSIONS: A specific
      pattern of extracellular matrix protein expression was found in relation to
      mechanical strain on human aortic valve cusp tissue and in mechanically
      stimulated human valvular fibroblasts. This new insight into the process of
      aortic valve degeneration may be important for further therapeutic approaches to
      ameliorate the progression or even the initiation of potential aortic valve
      stenosis.

PMID- 19853098
TI  - A comparison of mechanical properties of materials used in aortic arch
      reconstruction.
AB  - BACKGROUND: Differences in the mechanical properties of aortic tissues and
      replacement materials can have unwanted hemodynamic effects leading to graft
      failure. The aim of this experimental study was to compare the mechanical
      properties of different graft-patch materials used in aortic arch reconstruction
      with those of healthy and dilated human ascending aortas (AAs). METHODS: Four
      square samples were taken from 30 healthy (n = 120) and 14 dilated (n = 56) AA
      rings and from 34 human pericardial sections (fresh [n = 68] and Carpentiers
      solution fixed [n = 68]). In addition, square samples from commercial bovine
      pericardium (n = 14) were also compared with woven Dacron grafts (n = 24) and
      tested biaxially. Stress-strain curves (0% to 30%) were generated using a biaxial
      tensile tester to quantify the anisotropic properties and stiffness of the
      materials at 37 degrees C. RESULTS: We found significant differences in stiffness
      and anisotropy among all material types. Fresh and fixed human pericardia, bovine
      pericardium, and Dacron were 9.5, 7.1, 16.4, and 18.4 times stiffer than dilated
      AAs, which was 1.3 times stiffer than healthy AAs under physiologic stretch. Only
      dilated and healthy AAs showed an increase in anisotropic properties with
      increasing strain. CONCLUSIONS: The significant differences in the mechanical
      properties among all materials we found are intended to increase the awareness of
      these differences in materials used in aortic reconstruction surgery. This
      finding suggests that improvements are needed in prosthetic material design to
      better mimic native tissue.

PMID- 19853099
TI  - Early clinical experience and echocardiographic results with a new semirigid
      mitral annuloplasty ring: the Sorin Memo 3D.
AB  - BACKGROUND: The Sorin Memo 3D (Sorin Biomedica Cardio S.r.L., Saluggia, Italy) is
      a new, complete semirigid annuloplasty ring. Clinical use, outcomes, and
      echocardiographic results are reported as an evaluation of its safety and
      efficacy in the treatment of mitral valve regurgitation (MVR). METHODS: This
      device was assessed in 63 patients (63.5% men; mean age, 70.2 +/- 10.3 years) who
      underwent MVR operations between January 2007 and June 2008. Functional
      classification was normal leaflet motion (type I; 1.6%), leaflet prolapse (type
      II; 66.7%), and restricted leaflet motion (type III; 31.7%). Valve disease was
      degenerative (68.25%), ischemic (25.4%), and nonischemic dilated cardiomyopathy
      (6.35%). RESULTS: Early mortality (< or = 30 days) was 3.3% (2 patients). Late
      mortality (11.2 +/- 5.1 months) was 4.9% (3 patients). No deaths were device
      related. Thromboembolic stroke occurred in 3.3% and endocarditis in 1.6%. Freedom
      from reoperation was 98.4%. At 6 months, MVR was grade 0/1 in 93.7% and grade 2+
      in 6.4%. Left end-diastolic ventricular diameters decreased significantly from
      59.3 +/- 6.9 mm preoperatively to 50.6 +/- 12.2 mm at 6 months, pulmonary
      arterial pressure decreased from 44.8 +/- 7.1 mm Hg to 38.4 +/- 5.5 mm Hg, and
      left ventricular ejection fraction increased significantly from 0.469 +/- 0.129
      to 0.582 +/- 0.106. New York Heart Association functional class was I in 81% and
      II in 13.8%. CONCLUSIONS: Early results indicate the Sorin Memo 3D ring safely
      and effectively minimizes secondary MVR resulting from all causes and preserves
      mitral annular flexibility and function at follow-up.

PMID- 19853100
TI  - Saddle shape of the mitral annulus reduces systolic strains on the P2 segment of
      the posterior mitral leaflet.
AB  - BACKGROUND: The three-dimensional saddle shape of the mitral annulus is well
      characterized in animals and humans, but the impact of annular nonplanarity on
      valve function or mechanics is poorly understood. In this study, we investigated
      the impact of the saddle shaped mitral annulus on the mechanics of the P2 segment
      of the posterior mitral leaflet. METHODS: Eight porcine mitral valves (n = 8)
      were studied in an in-vitro left heart simulator with an adjustable annulus that
      could be changed from flat to different degrees of saddle. Miniature markers were
      placed on the atrial face of the posterior leaflet, and leaflet strains at 0%,
      10%, and 20% saddle were measured using dual-camera stereophotogrammetry.
      Averaged areal strain and the principal strain components are reported. RESULTS:
      Peak areal strain magnitude decreased significantly from flat to 20% saddle
      annulus, with a 78% reduction in the measured strain over the entire P2 region.
      In the radial direction (annulus free edge), a 44.4% reduction in strain was
      measured, whereas in the circumferential direction (commissure-commissure), a 34%
      reduction was measured from flat to 20% saddle. CONCLUSIONS: Nonplanar shape of
      the mitral annulus significantly reduced the mechanical strains on the posterior
      leaflet during systolic valve closure. Reduction in strain in both the radial and
      circumferential directions may reduce loading on the suture lines and potentially
      improve repair durability, and also inhibit progression of valve degeneration in
      patients with myxomatous valve disease.

PMID- 19853101
TI  - Invited commentary.

PMID- 19853102
TI  - Temperature dependence of cerebral blood flow for isolated regions of the brain
      during selective cerebral perfusion in pigs.
AB  - BACKGROUND: Hypothermic circulatory arrest (HCA) and antegrade selective cerebral
      perfusion (ASCP) are utilized for cerebral protection during aortic surgery.
      However, no consensus exists regarding optimal ASCP-temperature showing a
      tendency toward higher values during the last years. This study investigates
      regional changes of cerebral blood flow (CBF) during ASCP at two temperatures.
      METHODS: In this blinded study, 20 pigs (35 to 37 kg) were randomized to two
      groups. Animals were cooled to 10 minutes of HCA followed by 60 minutes of ASCP.
      Afterward the animals were perfused at 25 degrees C and 30 degrees C according to
      the study group. Fluorescent microspheres were injected at seven time points
      during the experiment to calculate total and regional CBF. Hemodynamics,
      cerebrovascular resistance (CVR) and cerebral metabolic rate of oxygen (CMRO(2))
      were assessed. Tissue samples from the cortex, cerebellum, hippocampus, and pons
      were taken for microsphere count. RESULTS: The CBF and CMRO(2) decreased
      significantly (p < 0.002) during cooling in both groups; it was significantly
      higher throughout ASCP in the 30 degrees C versus the 25 degrees C group (p =
      0.0001). These findings were similar among all brain regions, certainly at
      different levels. The CBF increased significantly (p = 0.002) during the early
      period of ASCP for analyzed regions and decreased significantly (p = 0.034) below
      baseline after 60 minutes of ASCP, reaching critical levels in the hippocampus
      and neocortex. The hippocampus turned out to have the lowest CBF, while the pons
      showed the highest CBF. Thirty minutes and more ASCP provides less CBF compared
      with baseline values at both temperatures. CONCLUSIONS: Antegrade selective
      cerebral perfusion improves CBF in all regions of the brain for a limited time.
      Our study characterizes the brain specific hierarchy of blood flow during ASCP.
      These dynamics are highly relevant for clinical strategies of perfusion.

PMID- 19853103
TI  - Invited commentary.

PMID- 19853104
TI  - Simplified management of hemodialysis-dependent patients undergoing cardiac
      surgery.
AB  - BACKGROUND: The mortality and morbidity rates are high after cardiac surgery in
      hemodialysis (HD)-dependent patients. To improve their outcomes, optimal
      perioperative managements should be discussed. METHODS: A retrospective analysis
      of 245 HD patients who underwent cardiac surgery between 1994 and 2007 was
      conducted. The basic management strategies were (1) low-potassium HD for 2 days
      before surgery, (2) only hemofiltration during cardiopulmonary bypass, and (3)
      start of regular intermittent HD on the first postoperative day. Continuous
      venovenous hemodiafiltration was applied only for patients with hemodynamic
      instability. RESULTS: The causes of renal failure included diabetic (n = 89,
      36%), glomerulonephritis (n = 49, 20%), and unknown (n = 75, 31%). The history of
      HD was 9.7 +/- 7.6 years. The operative procedures included coronary (n = 135),
      valve (n = 103), and others. The amount of intraoperative ultrafiltration was
      6,123 +/- 324 mL during cardiopulmonary bypass for 197 +/- 67 minutes. Two
      hundred eight patients (85%) were managed with only intermittent HD, whereas 36
      patients (15%) needed continuous venovenous hemodiafiltration. The use of
      continuous venovenous hemodiafiltration significantly declined during the year
      (26% before 2003 and 3% after 2003; p < 0.001). The amount of fluid removal on
      the first postoperative day was 1,297 +/- 81 mL. The hospital mortality was 9.7%
      with the causes including infection (n = 11), cardiac events (n = 6),
      gastrointestinal events (n = 5), and stroke (n = 2). A multivariate logistic
      regression analysis revealed that selection of intermittent HD or continuous
      venovenous hemodiafiltration was not related to the hospital mortality.
      CONCLUSIONS: Simplified management only with intermittent HD can be safely
      performed in most HD-dependent patients undergoing cardiac surgery.

PMID- 19853105
TI  - Prospective, randomized clinical trial of the FloSeal matrix sealant in cardiac
      surgery.
AB  - BACKGROUND: Topical hemostatic agents composed of a gelatin-based matrix and
      thrombin have been reported to be effective, in addition to traditional means, in
      terminating bleeding during cardiac operations. We compared a hemostatic matrix
      sealant agent (FloSeal; Baxter Inc, Deerfield, IL) with alternative topical
      hemostatic agents in a mixed cohort of elective cardiac and thoracic aortic
      operations. METHODS: Following sample size calculation, in a prospective
      randomized study design, 209 patients were treated with FloSeal matrix sealant
      (FloSeal group) and 206 patients received alternative agents as topical
      hemostatic materials (comparison group). FloSeal is composed of a self-expandable
      gelatin matrix component and purified bovine thrombin. Comparisons included
      hemostatic patches or sponges composed of either oxidized regenerated cellulose
      or purified porcine skin gelatin. Study endpoints were the following: rate of
      successful intraoperative hemostasis (identified by cessation of bleeding) and
      time required for hemostasis; overall postoperative bleeding; rate of transfusion
      of blood products; rate of surgical revision for bleeding; postoperative
      morbidity; and intensive care unit stay. RESULTS: Statistically higher rates of
      successful hemostasis and shorter time-to-hemostasis were observed in the FloSeal
      group (p < 0.001 both). Time-to-event analysis confirmed this finding (p =
      0.0025). Postoperative bleeding and rate of transfusion of blood products were
      statistically decreased in the FloSeal group (p < 0.001 both). Rates of revision
      for bleeding and of minor complications were not statistically different among
      groups in the overall cohort, but were significantly lesser in the FloSeal group
      if only patients with overt intraoperative bleeding are considered (p = 0.04
      both). The advantages observed in the FloSeal group were not offset in patients
      undergoing systemic hypothermia. CONCLUSIONS: The topical hemostatic agent used
      in the FloSeal group is effective in terminating intraoperative bleeding as an
      adjunct to traditional surgical methods for stopping bleeding. Its judicious use
      is associated with lesser need for transfusion of blood products and rate of
      revision for bleeding. Its cost-utility profile should be addressed in dedicated
      trials.

PMID- 19853106
TI  - Current surgical management of ascending aortic aneurysm in children and young
      adults.
AB  - BACKGROUND: The low incidence of aortic aneurysm among children and young adults
      limits information about etiology, surgical indications, procedures of choice,
      and operative results. METHODS: From 2003 to 2008, 35 patients aged 7 to 35 years
      (mean 21) underwent replacement of the ascending aorta for 19 ascending aortic
      aneurysms and 16 aortic root aneurysms. Underlying diseases included 10
      congenital aortic stenoses, 10 bicuspid aortic valves, 8 congenital heart
      diseases, 6 Marfan syndromes, and 1 aortitis. RESULTS: Indications for surgery
      were maximal diameter of 200% of normal for isolated aneurysms, and 160% of
      normal in case of associated aortic valve dysfunction or symptoms. Operative
      procedures included 27 ascending aortic replacements with or without aortic valve
      replacement (including 22 conduits) and 8 valve-sparing operations, performed in
      6 patients with Marfan syndrome and 2 with congenital heart diseases. There was 1
      in-hospital death. Thirty-four patients survived the operation and are in New
      York Heart Association functional class II or less at a maximum of 5 years of
      follow-up. All patients are free from reoperation, but 1 patient had a
      thromboembolic event. Aortic valve function is good in all 8 patients after the
      valve-sparing operation. CONCLUSIONS: Ascending aortic aneurysm in children and
      young adults was surgically treated with excellent midterm outcome. A diameter of
      200% of normal was the indication for surgery; however, in case of associated
      lesions, smaller diameters should be considered for surgery. Conduit implantation
      is the gold standard. Valve-sparing operation can be performed in selected
      patients with encouraging results.

PMID- 19853107
TI  - A comparative study of mechanical and homograft prostheses in the pulmonary
      position.
AB  - BACKGROUND: Homografts (HGs) are considered the gold standard for pulmonary valve
      replacement. However, to avoid further operations, the use of mechanical valves
      (MVs) might be considered, especially in patients who had had multiple prior
      operations or require an additional MV in another position. METHODS: Data of 19
      patients with MVs were compared with 19 patients with HGs, matched for age, sex,
      and follow-up time. Development of gradient and regurgitation were analyzed using
      hierarchical multilevel modeling. Mean follow-up time was 5.8 +/- 2.6 years.
      RESULTS: The initial pressure gradient was significantly lower in HGs compared
      with MVs (11.7 mm Hg vs 19.2 mm Hg, p = 0.006), but the annual increase was
      significantly higher in HGs compared with MVs (4.0 mm Hg/year vs 1.1 mm Hg/year,
      p = 0.008). The initial regurgitation grade was significantly higher in HGs
      compared with MVs (0.81 vs 0.37, p < 0.001), and the annual increase was also
      significantly higher in HGs compared with MVs (0.09 grade/year vs -0.01
      grade/year, p < 0.001). Reintervention was required in 3 HGs (stenosis), and in 2
      MVs (thrombosis after irregular anticoagulation, dysfunction due to ingrowth of
      tissue). Freedom from reintervention was not significantly different between both
      groups (p = 0.32). CONCLUSIONS: The hemodynamic performances of MVs are superior
      to HGs because gradient and regurgitation develop significantly slower. However,
      this does not lead to lower reintervention rates. Because reoperations of MVs can
      be prevented by appropriate surgical technique and strict anticoagulation, MVs
      should be considered for the pulmonary position, especially in patients who
      require anticoagulation treatment for additional MVs or rhythm disturbances.

PMID- 19853108
TI  - Invited commentary.

PMID- 19853109
TI  - Ring-enforced right ventricle-to-pulmonary artery conduit in Norwood stage I
      reduces proximal conduit stenosis.
AB  - BACKGROUND: An increasing number of surgeons prefer to place a conduit from the
      right ventricle to the pulmonary artery at the time of the Norwood stage I
      procedure. Proximal conduit stenoses have led us to modify this technique by
      using ring-enforced polytetrafluoroethylene conduits. METHODS: Angiograms of 24
      patients with conventional conduits (CC) and 28 patients with ring-enforced
      conduits (RC) before partial bidirectional cavopulmonary anastomosis were
      analyzed. The degree of conduit stenosis on three different levels--proximal
      anastomosis, substernal part of the conduit, and distal anastomosis--was compared
      between the two groups. RESULTS: In the RC group, the extent of conduit stenosis
      at the level of proximal anastomosis and within the substernal proximal third of
      the conduit was minimized (23% +/- 22% vs 45% +/- 22%, p = 0.001, and 7% +/- 6%
      vs 49% +/- 26%, p < 0.001, respectively). At the level of the anastomosis with
      the pulmonary arteries, results were similar in the RC group (24% +/- 14%) vs CC
      group (31% +/- 15%, p = 0.103). Significantly fewer patients in the RS group
      required urgent intervention (dilatation +/- stenting) or early stage II
      operation (1 vs 6 patients, p = 0.034). CONCLUSIONS: The use of a ring-enforced
      polytetrafluoroethylene conduit between the right ventricle and the pulmonary
      artery in Norwood stage I palliation effectively prevents substernal compression
      and reduces interstage morbidity.

PMID- 19853110
TI  - Pericardiectomy for pericarditis in the pediatric population.
AB  - BACKGROUND: Pericarditis requiring pericardiectomy is uncommon in the pediatric
      population. The aim of this study is to characterize our experience with this
      subset of patients. METHODS: Between February 1978 and May 2008 pericardiectomy
      was performed on 27 pediatric patients (25 male). The indication for surgery was
      inflammatory pericarditis in 16 and constrictive pericarditis in 11. Mean age was
      16.7 years (range, 3 to 21 years). Chest pain was the most common presenting
      complaint. Median duration of symptoms prior to operation was 1 year. Most
      patients had aggressive pharmacologic treatment prior to operation. Before
      pericardiectomy, 10 patients were hospitalized for treatment of symptoms, 15
      underwent pericardiocentesis, and 3 had a prior partial pericardiectomy. RESULTS:
      Twenty-one patients underwent complete pericardiectomy, 3 a biventricular
      pericardiectomy, and 3 a completion pericardiectomy. Pathologic histology of all
      specimens was positive for pericarditis. Pericardial cultures were obtained in 13
      cases with bacteria retrieved from only 2 specimens. Median length of stay was 7
      days, and the majority had an uneventful postoperative course. The one early
      mortality was due to acute hepatic failure in a patient with radiation-induced
      heart disease, 155 days after operation. After median follow-up of 1 year,
      complete resolution of symptoms was achieved in 89% of patients. CONCLUSIONS: In
      properly selected pediatric patients, complete pericardiectomy can be performed
      with good outcomes. Although the etiology of pericardial irritation is frequently
      elusive, resolution of symptoms can be expected in most patients. Confronted with
      medically refractory pericarditis, earlier consideration for pericardiectomy may
      be warranted.

PMID- 19853111
TI  - Transcatheter closure of postoperative residual perimembranous ventricular septal
      defects.
AB  - BACKGROUND: The presence of postoperative residual perimembranous ventricular
      septal defect (PmVSD) is relatively uncommon. However, reoperation might be
      associated with an increased surgical risk. Transcatheter device closure is an
      alternative strategy for management of postoperative residual defects. METHODS:
      Between July 2002 and November 2008, transcatheter closure of postoperative
      residual PmVSDs was attempted in 26 patients (11 male, 15 female). Symmetric and
      asymmetric PmVSD occluders were used. RESULTS: The diameter of residual defects
      was from 3 mm to 10 mm (mean 6.3 +/- 2.3 mm) on transthoracic echocardiography.
      In 24 of 26 patients, the residual defects were successfully closed. No direct
      residual defect was found on left ventriculography after the procedure. Total
      occlusion rate was 62% (15 of 24) at completion of the procedure, rising to 71%
      (19 of 24) at one week and 96% (23 of 24) during the follow-up. Twenty patients
      had only one device implanted, whereas 4 patients had two devices implanted. The
      waist size of occluders used ranged from 5 mm to 12 mm (mean 8.6 +/- 2.5 mm). One
      patient presented with complete atrioventricular block 3 days after the procedure
      and recovered 2 weeks later. Hemolysis occurred in 3 patients after the procedure
      within 12 hours. These patients recovered 4 weeks, 4 days, and 8 days later,
      respectively. During follow-up, the devices were in a stable position with
      optimal shapes. No late complications were observed. CONCLUSIONS: Transcatheter
      closure of postoperative residual PmVSDs is possible without the need for
      reoperation. The early and midterm prognosis of patients with transcatheter
      closure is good.

PMID- 19853112
TI  - Surgical lung resection for severe hemoptysis.
AB  - BACKGROUND: The role of surgical lung resection in the management of severe
      hemoptysis has evolved after advances in interventional radiology. We sought to
      describe the indications for surgical lung resection in such patients and to
      identify predictive factors of postoperative complications. METHODS: This study
      is a retrospective analysis (May 1995 to July 2006) of consecutive patients
      referred to the intensive care unit of a tertiary hospital for severe hemoptysis
      who underwent surgical lung resection. RESULTS: Among 813 patients referred for
      severe hemoptysis, 111 underwent surgical lung resection. Interventional
      radiology had been first attempted in 87 patients (78%); 68 underwent surgery
      because of a failed procedure (n = 28) or bleeding persistence or recurrence
      within 72 hours despite a completed procedure (n = 40); 19 patients underwent
      surgery after bleeding control. The remaining 24 patients (22%) were directly
      referred to the surgeon (5 for emergency surgery). Overall, surgery was performed
      in emergency (n = 48), scheduled after bleeding control (n = 48), or planned
      after discharge (n = 15). The main indications for surgery were mycetoma, cancer,
      bronchiectasis, and active tuberculosis. Surgery for mycetoma (odds ratio, 9.4;
      95% confidence interval, 2.8 to 32), emergency surgery (odds ratio, 5.3; 95%
      confidence interval, 1.8 to 16), and pneumonectomy (odds ratio, 4.7; 95%
      confidence interval, 1.2 to 18) independently predicted complications. Fifteen
      patients died in the intensive care unit, of whom 14 underwent emergency surgery.
      Chronic alcoholism (odds ratio, 4.6; 95% confidence interval, 1.1 to 19), the
      need for mechanical ventilation or vasoactive drugs on admission (odds ratio,
      8.2; 95% confidence interval, 1.9 to 35), and blood transfusion before surgery
      (odds ratio, 8; 95% confidence interval, 1.5 to 42) predicted mortality.
      CONCLUSIONS: Attempting at controlling bleeding with first-line nonsurgical
      approaches appears necessary to optimize the operative conditions and improve
      outcome of patients with severe hemoptysis.

PMID- 19853113
TI  - Invited commentary.

PMID- 19853114
TI  - The influence of surgeon specialty on outcomes in general thoracic surgery: a
      national sample 1996 to 2005.
AB  - BACKGROUND: While general thoracic surgical procedures are performed by several
      different surgical subspecialties, debate remains as to whether surgeon specialty
      impacts outcomes. METHODS: The Nationwide Inpatient Sample (NIS) was queried for
      procedure codes for pneumonectomy, lobectomy, limited lung resection, and
      decortication. We constructed multivariate logistic regression models to
      calculate odds of hospital mortality or length-of-stay (LOS) greater than 14 days
      (a marker of morbidity), adjusted for age, sex, patient comorbidities, hospital
      setting, and surgeon specialty. A surgeon was considered general thoracic if they
      performed greater than 75% general thoracic operations and less than 10% cardiac
      operations, Cardiac if greater than 10% cardiac operations, and general surgeon
      if less than 75% general thoracic and less than 10% cardiac operations. A second
      set of models additionally adjusted for procedure-specific hospital and surgeon
      volume. RESULTS: From 1996 to 2005, the NIS estimates 41,808 pneumonectomies,
      321,767 lobectomies, 75,200 limited lung resections, and 149,318 decortications
      were performed in the United States. For all procedures studied, general thoracic
      surgeons had significantly decreased odds-of-death and LOS greater than 14 days
      compared with general surgeons. Cardiac surgeons had significantly decreased LOS
      greater than 14 days for all operations and decreased odds-of-death for
      decortications, lobectomy, and limited lung resection compared with general
      surgeons. When further adjusted for surgeon volume, most differences in odds-of
      death were no longer present; however, significantly decreased LOS greater than
      14 days largely persisted for both general thoracic and cardiac surgeons.
      CONCLUSIONS: The majority of general thoracic surgical operations in the United
      States are performed by surgeons not specializing in thoracic surgery. Both
      general thoracic surgeons and cardiac surgeons achieve better outcomes than
      general surgeons. Differences in mortality may be more dependent on surgeon
      volume than subspecialty. Differences in morbidity are significantly impacted by
      surgeon specialty and volume.

PMID- 19853115
TI  - Long-term results of sleeve lobectomy in the management of non-small cell lung
      carcinoma and low-grade neoplasms.
AB  - BACKGROUND: The objective of this study was to evaluate the operative mortality,
      morbidity, and long-term survival of sleeve lobectomy for non-small cell lung
      cancer and low-grade neoplasms. We evaluated the effects of neoadjuvant therapy
      on the bronchial anastomotic complication rate and determined whether sleeve
      lobectomy performed in patients with N1 disease resulted in decreased overall
      survival. METHODS: This study is a retrospective review of 196 patients who
      underwent sleeve lobectomy. One hundred twenty-five patients had non-small cell
      lung cancer. There were 117 men (59.7%) and 79 women (40.3%) with a mean age of
      54 years. Sixteen patients (13%) received neoadjuvant therapy. Fifty-six patients
      with N1 disease underwent sleeve lobectomy. RESULTS: There were 4 (2.0%)
      postoperative deaths. The postoperative morbidity rate was 36.7%. Four patients
      (2.0%) experienced bronchopleural fistulas. Multivariate analysis demonstrated
      that age older than 70 years (p = 0.02) and the diagnosis of non-small cell lung
      cancer (p = 0.0002) were risk factors for postoperative complications.
      Multivariate analysis also demonstrated that neoadjuvant therapy predicted
      anastomotic complications (p = 0.01). For non-small cell lung cancer patients,
      the 5-year survival rate was 44%. The 5-year survival rates for patients with
      pathologic N0 disease and N1 disease were 52.6% versus 39.3%, respectively (p =
      0.205). CONCLUSIONS: Sleeve lobectomy can be performed with minimal bronchial
      anastomotic complications and low postoperative mortality. In our study,
      neoadjuvant therapy for non-small cell lung cancer adversely influenced the rate
      of anastomotic complications. Performing sleeve lobectomy for patients with N1
      disease was not associated with decreased overall survival rates.

PMID- 19853116
TI  - The prognostic impact of main bronchial lymph node involvement in non-small cell
      lung carcinoma: suggestions for a modification of the staging system.
AB  - BACKGROUND: The therapeutic strategies for non-small cell lung carcinoma (NSCLC)
      with N1 and N2 disease differ remarkably. Debate exists about the definition of
      the borderline between N1 and N2 stations. This study evaluated the prognostic
      effect of N1 disease, especially focused on the significance of the main
      bronchial node (No. 10) vs N2 disease. METHODS: The records of 1601 patients who
      underwent complete pulmonary resection for NSCLC were reviewed to examine the
      clinical features of lymph nodal involvement. RESULTS: There were 1086 patients
      (67.8%) with pN0 disease, 202 (12.6%) with pN1, and 274 (17.1%) with pN2 disease;
      overall 5-year survival rates were 74.7%, 56.1% and 28.9%, respectively (p <
      0.001). Overall 5-year survival rates were 60.2% in hilar N1 and 49.6% in
      intralobar N1. Overall 5-year survival rates were 58.6% in N1 without node 10 and
      35.1% in N1 with node 10. A significant difference was observed between N0 and N1
      without node 10 (p < 0.001), and N1 without node 10 and N1 with node 10 (p =
      0.033); however, the difference between N1 with node 10 and N2 was not
      significant. The status of node 10 involvement was an independent prognostic
      factor of pN1 patients, as well as age and gender. CONCLUSIONS: Patients with
      node 10-positive N1 disease have an unfavorable prognosis, and the disease
      behaves like N2 disease. The definition of clear borderline between N1 and N2 is
      mandatory to achieve a uniform classification map. This study offers further
      information for clinical and therapeutic purposes.

PMID- 19853117
TI  - Risk factor comparison and clinical analysis of early and late bronchopleural
      fistula after non-small cell lung cancer surgery.
AB  - BACKGROUND: We retrospectively analyzed risk factors for late bronchopleural
      fistula after non-small cell lung cancer (NSCLC) surgery and compared with those
      for early bronchopleural fistula. METHODS: In all, 6,239 patients with NSCLC who
      underwent surgery were studied, and clinical risk factors were examined by
      univariate and multivariate analysis. This study included 23 patients (0.38%)
      with late bronchopleural fistula and 43 patients (0.65%) with early
      bronchopleural fistula among all 6,239 patients. Follow-up data were recorded
      until December 2005 or until death. Statistical significance was calculated using
      the log rank test. RESULTS: By univariate analysis, patients with radiotherapy
      after operation, pneumonia after operation, pneumonectomy, and advanced age were
      related to higher risk of bronchopleural fistula. In the multiple logistic
      regression models, both pneumonia and operative procedure were among the
      independent risk factors of early and late bronchopleural fistula. Early
      bronchopleural fistula was observed primarily in the aged. Late bronchopleural
      fistula was associated with postoperative radiotherapy. The average intervals of
      bronchopleural fistula between pneumonectomy and lobectomy were significantly
      different. Compared with the mortality rate of late bronchopleural fistula (0%),
      the mortality rate of early bronchopleural fistula (11.6%) was significantly
      higher. CONCLUSIONS: There are both similarities and differences between the risk
      factors for early and late bronchopleural fistula. We should analyze the
      different reasons for the occurrence of bronchopleural fistula, and adopt
      different preventive measures. Different follow-up should be provided for the
      different operations.

PMID- 19853118
TI  - Stereotactic radiosurgery for the treatment of lung neoplasm: experience in 100
      consecutive patients.
AB  - BACKGROUND: Surgical resection is the standard of care for patients with
      resectable non-small cell lung cancer or selected patients with pulmonary
      metastases. Stereotactic radiosurgery may offer an alternative option for high
      risk patients who are not surgical candidates. We report our initial experience
      with stereotactic radiosurgery in the treatment of lung neoplasm in 100
      consecutive patients. METHODS: Patients who were medically inoperable were
      offered stereotactic radiosurgery. Thoracic surgeons evaluated all patients,
      placed fiducials, and performed treatment planning in collaboration with
      radiation oncologists. Initially, a median dose of 20 Gy prescribed to the 80%
      isodose line was administered in a single fraction, and this was subsequently
      increased to a total of 60 Gy in three fractions. The primary end point evaluated
      was overall survival. RESULTS: We treated 100 patients (median age, 70 years; 51
      men, 49 women) with stereotactic radiosurgery: 46 (46%) with primary lung
      neoplasm, 35 (35%) with recurrent cancer, and 19 (19%) with pulmonary metastases.
      The median follow-up was 20 months. The median overall survival was 24 months.
      Local recurrence occurred in 25 patients. The probability of 2-year overall
      survival was 50% for the entire group, 44% for primary lung cancer, 41% for
      recurrent cancer, and 84% for metastatic cancer. CONCLUSIONS: Our initial
      experience indicates that stereotactic radiosurgery has reasonable results in
      these high-risk patients. Resection continues to remain the standard treatment;
      however, stereotactic radiosurgery may offer an alternative in high-risk
      patients. Further prospective studies with different dose schema are needed to
      evaluate the efficacy of stereotactic radiosurgery.

PMID- 19853119
TI  - Image-guided radiofrequency ablation of lung neoplasm in 100 consecutive patients
      by a thoracic surgical service.
AB  - BACKGROUND: Surgical resection is the standard of care for patients with
      resectable non-small cell lung cancer or selected patients with pulmonary
      metastases. However, for high-risk patients radiofrequency ablation (RFA) may
      offer an alternative option. The objective of this study was to evaluate computed
      tomography-guided RFA for high-risk patients and report our initial experience in
      100 consecutive patients by a thoracic surgical service. METHODS: Medically
      inoperable patients were offered RFA. Thoracic surgeons evaluated and performed
      RFA under computed tomography guidance. Patients were followed in the thoracic
      surgery clinic. The primary end point evaluated was overall survival. RESULTS:
      One hundred patients underwent image-guided RFA for lung neoplasm (40 men, 60
      women; median age, 73.5 years; range, 26 to 95 years). Forty-six patients (46%)
      with primary lung neoplasm, 25 patients (25%) with recurrent cancer, and 29
      patients (29%) with pulmonary metastases underwent RFA. The mean follow-up for
      alive patients was 17 months. The median overall survival for the entire group of
      patients was 23 months. The probabilities of 2-year overall survival for the
      entire group, primary lung cancer patients, recurrent cancer patients, and
      metastatic cancer patients were 49% (95% confidence interval, 37 to 60), 50% (95%
      confidence interval, 33 to 65), 55% (95% confidence interval, 25 to 77), and 41%
      (95% confidence interval, 19 to 62), respectively. CONCLUSIONS: Our experience
      indicates that image-guided RFA done by the thoracic surgeons is feasible and
      safe in high-risk patients with lung neoplasm with reasonable results in patients
      who are not fit for surgery. Thoracic surgeons can perform RFA safely, and should
      continue to investigate this new image-guided modality that may offer an
      alternative option in medically inoperable patients.

PMID- 19853120
TI  - Lung transplantation and donation after cardiac death: a single center
      experience.
AB  - BACKGROUND: Lung donation after cardiac death (DCD) can enlarge the donor pool.
      Single-center reports have shown comparable outcomes after lung transplantation
      using conventional donors versus DCD in small numbers of patients. METHODS: We
      performed a retrospective review of DCD experience at a single lung transplant
      program using a prospective database. RESULTS: Between January 2003 and April
      2008, 293 lung transplantations were performed, including 11 bilateral
      transplantations (3.7%) using DCD lungs. Similar criteria were used to assess
      donor quality. The hospital mortality for DCD recipients was 2 of 11 (18%) and
      overall mortality was 4 of 11 (36%) by 18 months of follow-up. Seven DCD patients
      (64%) are alive with a median follow-up of 32 months. The DCD group was
      comparable to the control group in age and ischemic times. The 4 deaths, when
      compared with 7 DCD survivors, had longer ischemic time (293 minutes versus 232
      minutes) and a higher incidence of nonlocal donors (3 of 4 versus 1 of 7).
      CONCLUSIONS: At our center, early outcomes after DCD lung transplantations are
      somewhat inferior to those of series from other centers but approach national
      averages for conventional lung transplantation. Thus, DCD lung transplantation
      has the potential to increase the donor pool but must be offered cautiously.

PMID- 19853121
TI  - Survival after single versus bilateral lung transplantation for high-risk
      patients with pulmonary fibrosis.
AB  - BACKGROUND: Whether single lung transplantation (SLT) or bilateral lung
      transplantation (BLT) is optimal for patients with severe idiopathic pulmonary
      fibrosis (IPF) is unknown. We examine a large multi-institutional cohort of high
      risk IPF patients to address this question. METHODS: We retrospectively reviewed
      United Network for Organ Sharing data to identify 1,256 lung transplant (LTx)
      recipients with IPF between 2005 and 2007. Risk of 30-day, 90-day, and 1-year
      mortality for SLT versus BLT was examined across levels of the lung allocation
      score (LAS [both continuous with incorporation of interaction terms and
      categorized by LAS quartiles]). Multivariable analysis was conducted through Cox
      proportional hazards regression. RESULTS: Lung allocation score quartiles were as
      follows: quartile 1, 29.8 to 37.8, n = 315; quartile 2, 37.9 to 42.4, n = 313;
      quartile 3, 42.5 to 51.9, n = 314; and quartile 4, 52.0 to 94.1, n = 314.
      Overall, 21.1% more patients received BLT in the highest LAS quartile (59.5%)
      than in the lowest LAS quartile (38.4%, p < 0.05). In patients at highest risk,
      BLT was associated with a 14.4% decrease in mortality at 1 year after LTx. This
      survival benefit was confirmed on univariate analysis (hazard ratio 1.90 [95%
      confidence interval: 1.16 to 3.13], p = 0.01) and multivariable analysis (hazard
      ratio 2.09 [95% confidence interval: 1.07 to 4.10], p = 0.03) as well as in
      sensitivity analyses incorporating pulmonary hypertension and maximizing follow
      up. There were no differences in the risk of death with SLT at 30 or 90 days
      after LTx in any quartile on unadjusted or multivariable adjusted analysis.
      CONCLUSIONS: We provide an initial examination of survival by procedure type and
      LAS score for LTx recipients with IPF. Bilateral LTx appears to offer advantages
      over SLT for high-risk patients.

PMID- 19853122
TI  - Surgery for recurrent pectus deformities.
AB  - BACKGROUND: Pectus repair in adults can be challenging. Standard repair has been
      the modified Ravitch procedure. More recently the minimally invasive Nuss
      procedure, used exclusively in children, has been introduced for correction of
      pectus deformities in adults. There is a paucity of data on which procedure is
      most appropriate for adults and even less information on the most appropriate
      operation for pectus recurrence in adults. The purpose of this study is to
      determine if any specific patient characteristic exists that places patients at
      an increased risk for recurrence and describe our management of recurrent pectus
      defects in adults. METHODS: We retrospectively reviewed the records of all
      patients (>16 years of age) who underwent primary or recurrent repair of pectus
      deformities from April 1999 through December 2006. RESULTS: Forty-eight patients,
      37 (77%) men and 11 women, underwent pectus repair with a median age of 28 years
      (range, 16 to 54 years). Indication for initial repair was pectus excavatum in 39
      (81%) and pectus carinatum in 9. The primary procedure was a modified Ravitch
      repair in 40 patients and a Nuss procedure in 8. Thirteen patients (27%)
      underwent reoperation for recurrence; 8 (62%) patients had undergone a previous
      Nuss procedure and 5 had a modified Ravitch repair. All reoperative patients had
      a primary pectus index (PI) greater than 4.0, while 8 (62%) also had an
      asymmetrical defect. All failed Nuss procedure patients underwent a modified
      Ravitch repair for correction, while the recurrent open repair patients required
      complex reconstructions. Results were good or excellent in greater than 90% of
      patients undergoing a reoperative procedure. CONCLUSIONS: Adults with severe
      pectus deformities (PI > 4.0) and asymmetric defects are at a greater risk of
      recurrence after a Nuss procedure. These patients may better be served with a
      modified Ravitch repair initially. Reoperation for failed pectus repair in adults
      can be performed safely with outstanding results.

PMID- 19853123
TI  - Solitary fibrous tumors of the pleura: an analysis of 110 patients treated in a
      single institution.
AB  - BACKGROUND: Solitary (localized) fibrous tumors of the pleura (SFTP) are rare
      slow-growing neoplasms that generally have a favorable prognosis. The aim of this
      paper is to evaluate the predictors of outcome in a series of 110 patients with
      SFTP. METHODS: The records of 110 patients (63 men; mean age 56.4 years; range,
      17 to 79) surgically treated for SFTP from July 1990 to February 2008, were
      evaluated for demographics, operative procedure, histopathology, morbidity,
      mortality, postoperative chemotherapy or radiotherapy, and long-term follow-up.
      RESULTS: Operative mortality was 0.9% (1 of 110) and the overall morbidity was
      10.9% (12 of 110). The main surgical approach was video-assisted thoracoscopic
      surgery (69 procedures with a conversion rate of 14.5%); 40 patients underwent
      thoracotomy and 1 had sternotomy. The visceral pleura was the site of origin in
      95 tumors, the parietal pleura in 13, the mediastinal pleura in 2 cases. Sixty
      three tumors were pedunculated, 35 were sessile, and 12 were inverted fibroma.
      Tumors were pathologically benign in 95 cases (86.4%), and malignant in 15
      (13.6%). Symptomatic patients presented with malignant tumors more often than
      asymptomatic (19.1% versus 9.5%). Overall 10-year survival rate was 97.5%. The
      overall disease-free survival rate was 90.8% (95.7% in benign cases and 67.1% in
      malignant cases; p < 0.05). Eight patients presented with recurrence of disease,
      4 cases of which were malignant and 4 were benign. CONCLUSIONS: Solitary fibrous
      tumor of the pleura is a rare disease that includes both benign and malignant
      variants.The outcome is mostly benign, with an overall 10-year survival rate of
      97.5%. Pathologically benign lesions show a better disease-free survival rate
      than malignant lesions (95.7% versus 67.1%; p < 0.05). Surgery is the gold
      standard of treatment as neither radiotherapy nor chemotherapy proved to be
      effective.

PMID- 19853124
TI  - Modified maximal thymectomy for myasthenia gravis: effect of maximal resection on
      late neurologic outcome and predictors of disease remission.
AB  - BACKGROUND: Although thymectomy is a standard practice of care in patients with
      myasthenia gravis, the best approach to thymic resection remains controversial.
      This study was conducted to assess the effect of maximal resection on neurologic
      outcome and identify predictors of disease remission. METHODS: Data of 78
      myasthenic patients who underwent modified maximal thymectomy during a 17-year
      period were retrospectively analyzed. The primary study end point was the
      achievement of complete remission. Separate analysis was performed for thymoma
      and nonthymoma patients regarding the factors predicting the neurologic outcome.
      RESULTS: No patients died perioperatively. Surgical morbidity was 7.7%. The rate
      of postoperative myasthenic crisis was 3.8%. Thymoma and nonthymoma patients
      experienced comparable complete stable remission prediction (74.5% vs 85.7% at 15
      years; p = 0.632). The absence of steroids in the preoperative medical treatment
      was statistically related to the prediction for complete stable remission in both
      thymoma (95% confidence interval [CI], 2.687 to 339.182, p = 0.006) and
      nonthymoma patients (95% CI, 1.607 to 19.183; p = 0.007) in multivariate
      analysis. In thymomatous myasthenia gravis, there was a statistically significant
      association between disease remission and the World Health Organization (WHO)
      histologic classification (95% CI, 0.262 to 0.827; p = 0.009). CONCLUSIONS:
      Maximal resections are recommended in myasthenic patients. Disease severity
      represents the prime determinant of the neurologic outcome after thymectomy. The
      neurologic outcome in patients after thymectomy may be statistically associated
      with the WHO classification subtypes but not necessarily with the aggressiveness
      of these tumors.

PMID- 19853125
TI  - Invited commentary.

PMID- 19853126
TI  - Colon interposition after esophagectomy with extended lymphadenectomy for
      esophageal cancer.
AB  - BACKGROUND: The purpose of this retrospective study was to investigate the
      feasibility of colon interposition procedures after esophagectomy with extended
      lymphadenectomy. METHODS: Between 1990 and 2008, 95 consecutive patients
      underwent colon interposition after esophagectomy with extended lymphadenectomy
      for esophageal cancer in our Institution. We reviewed clinical data and long-term
      survival, and also investigated the association between anastomotic leakage and
      clinicopathologic findings. RESULTS: We applied three-field lymphadenectomy to 71
      patients and two-field to 24 patients, by a right thoracotomy. Ninety-two
      patients underwent reconstruction by a retrosternal route, and a posterior
      mediastinal route was applied to only three patients. We performed hand-sewn
      anastomosis in the neck in all cases. Three patients required microvascular
      surgery. Sixty-one patients (64%) experienced postoperative morbidity, most
      commonly pulmonary complications. Anastomotic leakage occurred in 12 patients
      (13%). No colon conduit necrosis was detected. Overall mortality, including
      hospital mortality, was 5.3%. Dysphagia (39%) and diarrhea (38%) were common and
      stricture was low (6%) after discharge. The overall 5-year survival rate was 43%.
      During the latter period (1998 to 2008), when ileocolon grafts evolved as the
      primary choice for interposition, the rate of leakage decreased from 17% (1990 to
      1997) to 5.4%. No mortality was recorded during the latter period. CONCLUSIONS:
      Results from this study demonstrate that colon interposition after esophagectomy
      with extended lymphadenectomy is feasible and can have a favorable outcome.

PMID- 19853127
TI  - Invited commentary.

PMID- 19853128
TI  - A new epicardial lesion set for minimal access left atrial maze: the Dallas
      lesion set.
AB  - PURPOSE: Improvements in enabling technology have facilitated minimal access
      techniques to the surgical ablation of atrial fibrillation. A variety of lesion
      sets (usually targeting only the left atrium) have been used in attempts to
      ablate atrial fibrillation. We describe a new epicardial approach to apply a set
      of left atrial lesions, which are electrophysiologically equivalent to all the
      left atrial lesions of the Cox maze III while using minimal access techniques.
      DESCRIPTION: Using minimal access techniques, we have isolated the pulmonary
      veins and made connecting lesions on the dome of the left atrium to create a set
      of lesions electrophysiologically equivalent to all the left atrial lesions of
      the Cox maze III. Intraoperative electrophysiological evaluation is used to
      insure complete isolation across each lesion line. EVALUATION: Using these
      minimal access procedures, we have obtained a complete block across all lesion
      lines in all patients. CONCLUSIONS: These techniques have made it possible to
      perform the full Cox maze III left atrial lesion set with minimal access
      techniques.

PMID- 19853129
TI  - Calcium phosphate cements improve bone density when used in osteoporotic
      sternums.
AB  - PURPOSE: Calcium phosphate cements control bleeding and are safe to use in
      osteoporotic sternums during open heart surgery. We looked at the clinical and
      radiographic effects of this agent on bone healing. DESCRIPTION: Since March
      2006, 18 patients had calcium phosphate cement inserted in their sternal tables
      at heart surgery. They were followed-up by office visits and chest computed
      tomographic (CT) scans. All preoperative and postoperative CT chest scans were
      evaluated for cement absorption, bone replacement, and bone density. EVALUATION:
      Five preoperative and 41 postoperative CT chest scans were available for
      evaluation. Median interval from surgery to CT scan was 531 days (range, 3 to 966
      days). At follow-up there were neither clinical dehiscences nor nonunions of the
      sternums. Calcium phosphate cement appears to reabsorb quickly, but not
      completely. Five patients with pre-surgical CT chest scans demonstrated an
      average, improved bone density of 281.66 Hounsfield units at follow-up (p =
      0.006). CONCLUSIONS: In each patient, cement was replaced by new bone, and there
      is evidence that more bone is present as a result of cement use.

PMID- 19853130
TI  - Successful transapical aortic valve replacement in a patient with a previous
      mechanical mitral valve replacement.
AB  - In this case we illustrate our experience with transapical minimal invasive
      aortic valve replacement in a patient who previously underwent mitral valve
      replacement. The implantation did not interfere with the existing prosthesis and
      could even be used as a further landmark, helping height positioning of the
      aortic valve.

PMID- 19853131
TI  - Post-traumatic rupture of the anterolateral papillary muscle.
AB  - Rupture of cardiac valves as a consequence of nonpenetrating cardiac trauma is an
      uncommon phenomenon. We report the case of a 24-year-old patient with a "two
      stage" traumatic rupture of the anterolateral papillary muscle of the mitral
      valve, after a blunt chest trauma, who successfully underwent emergency mitral
      valve replacement.

PMID- 19853132
TI  - Prophylactic use of factor IX concentrate in a Jehovah's Witness patient.
AB  - In Jehovah's Witness patients, the use of red blood cells, platelets, and fresh
      frozen plasma is not optional. Various blood conservation techniques are
      available, but complex cardiac surgery remains a major challenge. The feasibility
      of fractions of "primary components" has not been fully considered in published
      case reports. For Jehovah's Witness patients who preoperatively give consent,
      factor IX concentrates may be acceptable for hemostatic therapy. We hereby
      describe a combination of "secondary components" to prevent excessive bleeding in
      a Jehovah's Witness patient undergoing complex replacement of the aortic arch.

PMID- 19853133
TI  - Surgical treatment of a thoracoabdominal aneurysm in Cogan's syndrome.
AB  - Cogan's syndrome is a rare systemic disease which occurs predominantly in
      children and young adults. It was originally described as the combination of
      interstitial keratitis and audiovestibular disturbance. The nonspecific symptoms
      of the patients can be associated with numerous of systemic manifestations and,
      most characteristic, cardiovascular involvement. It affects large vessels
      (Takayasu-like) and medium size (polyarteritis nodosa-like) vessels. Here a case
      of extensive thoracoabdominal aortic replacement in a 28-year-old woman with
      Cogan's syndrome due to the symptomatic aortic aneurysm is described.

PMID- 19853134
TI  - Acute thrombosis of abdominal aortic aneurysm during cardiac surgery.
AB  - Aortic thrombosis has been described in the medical literature as a rare and
      catastrophic complication of abdominal aortic aneurysms. However, it has only
      been reported once in cardiac surgical settings. We report a unique case of
      thrombosis of an abdominal aortic aneurysms during the course of cardiac surgery,
      in a fully anticoagulated patient on cardiopulmonary bypass. Prompt diagnosis and
      immediate surgical management were critical for a successful outcome.

PMID- 19853135
TI  - Syphilitic aortitis: an uncommon cause of acquired aortopulmonary fistula.
AB  - Cardiovascular syphilis has become a medical curiosity with the advent of
      widespread use of penicillin for the treatment of early syphilis. We report a
      case of a 37-year-old man who presented with sudden onset breathlessness that
      worsened insidiously for 1 year. Diagnosis of syphilitic aortopulmonary fistula
      was confirmed by aortography, contrast computed tomography, and histopathology.
      The patient underwent successful surgical correction. A high level of suspicion
      and awareness is needed for the diagnosis of this now rare disease. This entity
      is only amenable to surgical correction, even as existing surgical techniques
      need constant improvisation and individualization to each patient.

PMID- 19853136
TI  - Fibrosing mediastinitis and occlusion of pulmonary veins after radiofrequency
      ablation.
AB  - Pulmonary vein stenosis is a known complication of radiofrequency ablation; its
      incidence ranges from 8% to 50%. However, complete occlusion of unilateral
      pulmonary veins is uncommon. We report a case with radiofrequency ablation that
      was complicated by complete occlusion of pulmonary veins along with fibrosing
      mediastinitis, which we believe has not been previously reported.

PMID- 19853137
TI  - Parallel application of extracorporeal membrane oxygenation and the CardioWest
      total artificial heart as a bridge to transplant.
AB  - Circulatory assist devices are an increasingly common method of treating patients
      with refractory cardiogenic shock. We describe a patient who was a heart
      transplant candidate with biventricular failure who underwent CardioWest total
      artificial heart-temporary (SynCardia Inc, Tucson, AZ) implantation with
      extracorporeal membrane oxygenation to manage the patient's subsequent
      respiratory failure. After respiratory and hemodynamic stabilization, the
      CardioWest total artificial heart-temporary served as a successful 62-day bridge
      to-heart transplantation.

PMID- 19853138
TI  - Left ventricular aneurysm in a child with severe combined immunodeficiency
      syndrome.
AB  - We describe the case of a 23-month-old girl with combined immunodeficiency
      syndrome and a left ventricular aneurysm. Due to the size of the aneurysm and
      development of an intramural thrombus, repair was performed after confirmation of
      bone marrow transplant engraftment. Endoventricular circular patch plasty (Dor
      procedure) was performed, with excellent outcome and normalization of ventricular
      geometry and function.

PMID- 19853139
TI  - A symptomatic neonate with tetralogy of Fallot, an absent pulmonary valve, and a
      single coronary artery with a major fistula.
AB  - We present a case with a rare combination of tetralogy of Fallot with an absent
      pulmonary valve, and a single coronary artery with a major fistula to the main
      pulmonary artery. Myocardial ischemia developed in response to increasing shunt
      flow through the coronary fistula, resulting in heart failure. We ligated the
      coronary fistula and plicated the anterior wall of the dilated pulmonary arteries
      during the neonatal period. Complete repair through a transatrial-transpulmonary
      approach was performed at the age of 17 months. The postoperative course was
      excellent and the patient maintained a stable hemodynamic and respiratory state
      with no evidence of myocardial ischemia.

PMID- 19853140
TI  - Duplicate mitral valve in an infant with Shone's anomaly.
AB  - Duplication of mitral valve is a very rare anomaly. It is characterized by two
      independent mitral valve apparatuses (leaflets and annulus) and subvalvular
      apparatuses (chordae and papillary muscles) that function well by themselves. In
      this report, we present duplicate mitral valve with parachute chordal attachment
      and mitral stenosis in an infant. The patient was successfully treated with the
      reconstruction of the larger valve without any intervention to the smaller one.

PMID- 19853141
TI  - Isolated subclavian artery: anatomical and surgical considerations.
AB  - Isolated subclavial artery is a rare congenital anomaly. Herein we discuss a
      patient with isolated left subclavian artery and bilateral patent arterial ducts
      who underwent successful repair. We also describe the detailed anatomy of both
      recurrent nerves in this condition and embryology of the anomaly.

PMID- 19853142
TI  - Percutaneous atrioseptostomy for right heart failure after left pneumonectomy.
AB  - We present a case of right heart failure after left pneumonectomy as a result of
      an isolated, contralateral partial anomalous pulmonary venous return. We
      successfully treated this with percutaneous atrioseptostomy. For unstable
      patients with postoperative acute heart failure from an undetected partial
      anomalous pulmonary venous return, this minimally invasive procedure represents a
      useful primary option while allowing secondary conventional surgery if required.

PMID- 19853143
TI  - Successful treatment of infected residual pleural space after pulmonary resection
      with autologous platelet-leukocyte gel.
AB  - Complications of the residual pleural space after pulmonary resection have been
      reported to be between 5% and 40% depending on the type of resection, and they
      increase morbidity, mortality, hospital stays, and costs. The therapeutic use of
      autologous prepared platelet leukocyte-enriched gel is a relatively new
      technology for the stimulation and acceleration of soft tissue and bone healing.
      This gel can be applied to a diversity of tissue. We describe the case of a
      successful application through a chest tube of platelet leukocyte gel to treat an
      infected residual pleural space that developed after pulmonary lobectomy for lung
      cancer.

PMID- 19853144
TI  - Successful endobronchial seal of surgical bronchopleural fistulas using BioGlue.
AB  - Postoperative bronchopleural fistula is uncommon, but it is associated with a
      high mortality and morbidity, and a prolonged hospital stay. Surgical treatment
      is gold standard, but it can prove challenging especially in the presence of
      infection. We describe three cases of bronchopleural fistula that developed after
      surgery for lung cancer in 1 patient and for bronchiectasis in 2 patients. All
      were successfully treated endoscopically by direct application of albumin
      glutaraldehyde tissue adhesive (BioGlue; Cryolife Inc, Kennesaw, GA) through a
      rigid bronchoscope. Complete resolution was obtained in each patient within 24
      hours.

PMID- 19853145
TI  - Cystic seminoma with elevated value of carbohydrate antigen 19-9 in tumor fluid
      mimicking cystic teratoma.
AB  - The incidence of cystic lesions of anterior mediastinum is low, which is
      responsible for approximately 10% of anterior mediastinal tumors. We presented a
      special case of primary anterior mediastinal tumor with both prominent cystic
      change and extreme high carbohydrate antigen 19-9 level of cystic fluid here.
      From the finding of this case report, we suggested that the diagnosis of cystic
      anterior mediastinal tumors should include both cystic seminoma and mature cystic
      teratoma.

PMID- 19853146
TI  - Lipoblastoma: a rare mediastinal tumor.
AB  - Lipoblastoma is a rare benign mesenchymal tumor of embryonal fat that occurs
      almost exclusively in infants and children less than age 3. It is a benign tumor
      with a high recurrence rate. We present a case of mediastinal lipoblastoma in a
      21-month-old girl who presented with respiratory infection and progressive
      dyspnea. Complete surgical excision of the mass was achieved through a lateral
      thoracotomy. Her postoperative course was uneventful and the histopathologic
      examination proved that the mass was a lipoblastoma. We emphasize that this rare
      mediastinal tumor should be included in the differential diagnosis of infants
      having a mediastinal mass.

PMID- 19853147
TI  - Two cases of an enormous single-lung metastasis from synovial sarcoma.
AB  - Synovial sarcoma constitutes 8% to 10% of all sarcomas, and most commonly it
      affects adults in the third to fifth decades of life. This malignancy usually
      involves the extremities, and although local control by curative resection and
      adjuvant irradiation has improved, metastases develop in 40% of patients, with
      lung involvement in the metastatic process in 90% of cases. A single metastasis
      to the lungs from synovial sarcoma is rare, and a case of a large, single
      metastasis is even rarer. Herein, we present two cases of patients with an
      enormous metastatic synovial sarcoma that were successfully removed surgically.

PMID- 19853148
TI  - Repair of a postesophagectomy bronchogastric tube fistula with polyglactin mesh
      supported with a muscle flap.
AB  - A bronchogastric fistula is a very rare complication of transthoracic
      esophagectomy. We report a case of bronchogastric fistula after transthoracic
      esophagectomy caused by dehiscence of the staple line in the gastric tube, with
      subsequent erosion into the right main bronchus. The patient was managed
      successfully in two surgical stages. First, the bronchial defect was repaired
      using a polyglactin mesh covered by a serratus anterior muscle flap. Two months
      later, the esophagogastric continuity was restored with colon interposition.

PMID- 19853149
TI  - A rare complication of esophageal stent: spinal epidural abscess.
AB  - The esophageal stent is used extensively for a malignant stricture, and many
      complications have been reported. We present a case of esophageal cancer with
      surgical esophageal stenting. Spinal epidural abscess occurred postoperatively,
      and we believe that the pathogenesis may be related to the esophageal stent.

PMID- 19853150
TI  - Subaortic stenosis in an adult caused by two discrete membranes: a three
      dimensional transesophageal echocardiographic visualization.

PMID- 19853151
TI  - Minocycline-induced pigmentation of the aortic valve and sinuses of Valsalva.

PMID- 19853152
TI  - A modified composite valve Dacron graft for prevention of postoperative bleeding
      from the proximal anastomosis after Bentall procedure.
AB  - Bleeding is one of the most devastating complications of the Bentall procedure.
      We describe a simple, modified composite valve Dacron (DuPont, Wilmington, DE)
      graft to prevent bleeding from the proximal anastomosis between the graft and
      aortic annulus. The composite graft was modified by adding a short skirt of
      Dacron tube to a standard composite graft root. After the proximal end of the
      modified composite graft was implanted in the aortic annulus, the short skirt of
      Dacron tube was sewn to the remaining native aortic wall to wrap the proximal
      graft and aortic annular anastomosis. Our initial application of the modified
      composite graft demonstrated that this modified composite graft is an easy and
      effective way to prevent bleeding from the proximal anastomosis after the Bentall
      procedure.

PMID- 19853153
TI  - Double-valve endocarditis homograft and patch repair.
AB  - We present our technique for reconstruction of aortic valve, mitral valve, and
      aortomitral curtain in double-valve endocarditis with involvement of
      intervalvular fibrous body.

PMID- 19853154
TI  - Hybrid approach to repair of pulmonary venous baffle obstruction after atrial
      switch operation.
AB  - Pulmonary venous pathway obstruction is a late complication of the atrial switch
      operation for transposition of the great arteries. Gaining peripheral access to
      the pulmonary venous baffle obstruction to treat the obstruction with stent
      deployment is difficult if not impossible. We present three patients in which we
      used hybrid procedures in the operating room to relieve the pulmonary venous
      pathway obstructions.

PMID- 19853155
TI  - Bronchial flap closure of the right lower lobe bronchus.
AB  - We describe a novel method for closure of the bronchus intermedius, after right
      lower lobectomy, using a flap derived from the lower lobe apical segmental
      bronchus. We have successfully used this technique in an endobronchial carcinoid
      tumor occurring in a young man. It allowed middle lobe preservation despite a
      very proximal tumor position within the basal trunk bronchus. Adequate tumor
      margins were confirmed by on-table frozen section examination. This technique may
      have particular use in carcinoids or benign tumors.

PMID- 19853156
TI  - Cell-based therapy for ischemic heart disease: a clinical update.
AB  - Progenitor cell therapy is a promising treatment for ischemic heart disease.
      Early clinical trials of autologous bone marrow-derived progenitor cell therapy
      for acute and chronic myocardial ischemia showed modest functional improvements
      after cell delivery; however, the duration of these benefits remains unclear.
      Ongoing investigations continue to enhance our understanding of the mechanisms by
      which progenitor and stem cells function and how their survival and
      cardioprotective abilities can be improved. This review discusses: (1) relevant
      progenitor and stem cells in myocardial regenerative therapy, (2) routes of cell
      delivery to ischemic myocardium, (3) clinical trials investigating bone marrow
      derived progenitor cell therapy for myocardial ischemia, and (4) future
      directions of the field.

PMID- 19853157
TI  - When is the request of a surrogate too unreasonable to follow?

PMID- 19853159
TI  - Is there any prospective, randomized study to confirm significantly better
      angiographic radial artery conduit patency compared with saphenous vein graft
      patency?

PMID- 19853161
TI  - A patent left internal thoracic artery should not be dissected or clamped during
      reoperative cardiac surgery.

PMID- 19853162
TI  - Mechanism of delayed aortic injury in left-sided rib fractures.

PMID- 19853164
TI  - Direct true lumen cannulation in surgery for acute type A aortic dissection is a
      valuable but risky alternative.

PMID- 19853166
TI  - On the association between body mass index and Barrett's esophagus.

PMID- 19853167
TI  - Fabrication of the mandibular implant-supported fixed restoration using CAD/CAM
      technology: a clinical report.
AB  - The mandibular implant-supported fixed restoration is an appropriate treatment
      choice for patients with inadequate bone volume in the posterior mandible.
      Computer-aided design/computer-aided manufacturing (CAD/CAM) technology has
      broadened the scope and application for this treatment option. A milled titanium
      bar retaining individual all-ceramic zirconium oxide crowns, with composite resin
      replicating gingival tissues, is recommended as an acceptable variation for this
      type of prosthesis. An alternative method for fabricating a mandibular implant
      supported fixed restoration using CAD/CAM technology is described.

PMID- 19853168
TI  - The interdisciplinary management of a Class II division 1 malocclusion with an
      associated mandibular defect following surgical excision of fibromatosis: a
      clinical report.
AB  - Surgical excision of malignant or nonmalignant tumors of the maxillofacial region
      can result in significant anatomical loss/compromise. Correction of the residual
      defect can be complicated by the presence of an underlying malocclusion and can
      be a significant clinical challenge if large numbers of teeth have been lost in
      surgery. This clinical report discusses the interdisciplinary treatment to
      rehabilitate a patient with a history of surgical removal of fibromatosis.
      Treatment involved the use of osseointegrated implants to facilitate orthodontic
      correction of an underlying malocclusion. The implants were subsequently used in
      the prosthodontic rehabilitation of the residual surgical defect.

PMID- 19853169
TI  - A removable partial denture using an esthetically designed round-rest distal
      clasp on maxillary anterior abutment teeth: a clinical report.
AB  - A round-rest, distal depression clasp is suggested as an esthetic alternative to
      a conventional clasp for maxillary anterior teeth serving as abutments for a
      removable partial denture. A lingual round rest provides support for the
      prosthesis, and a mesiolingual reciprocating plate is present. A split minor
      connector engages a distal depression for retention. The facial surface of the
      abutment displays no metal and provides an esthetic result.

PMID- 19853170
TI  - Prospective observation of CAD/CAM titanium ceramic single crowns: a three-year
      follow up.
AB  - STATEMENT OF PROBLEM: Computer-aided design/computer-aided manufacturing
      (CAD/CAM) titanium ceramic restorations were developed with the potential for
      replacing expensive, high noble metal ceramic restorations. However, there is a
      lack of information about the clinical performance of CAD/CAM titanium ceramic
      single crowns. PURPOSE: The purpose of this study was to evaluate CAD/CAM
      titanium ceramic single crowns after 3 years in function. MATERIAL AND METHODS: A
      total of 41 crowns were fabricated for 21 patients. The titanium copings were
      CAD/CAM milled (Everest CAD/CAM system) with an even thickness of 0.5 mm, and low
      fusing veneering porcelain (Vita Titanium Porcelain) was added incrementally. The
      crowns were cemented using zinc phosphate cement after confirming that there were
      no mechanical and biological complications. The patients were recalled at 12, 24,
      and 36 months after cementation to examine the presence of any complications and
      measure periodontal parameters such as probing depth (PD), bleeding on probing
      (BOP), and plaque index (PI). The success and survival rates were estimated using
      the Kaplan-Meier analysis. RESULTS: The success rate of CAD/CAM titanium ceramic
      crowns with regard to mechanical complications was 82.3% (95% confidence
      interval: 71.2% to 95.1%). The cumulative survival rate of the crowns was 94.9%
      (95% confidence interval: 88.3% to 100%) after 3 years. No biological
      complications were observed. At the end of the follow up, PD was 2.93 mm,
      percentile of surface with BOP was 29.2, and PI was 0.31. CONCLUSIONS: The
      clinical performances of the CAD/CAM titanium ceramic crowns for 3 years were
      acceptable, with no biologic complications and a high cumulative survival rate.

PMID- 19853171
TI  - Interactions between impression materials and immediate dentin sealing.
AB  - STATEMENT OF PROBLEM: Immediate dentin sealing is a new strategy in which a
      dentin bonding agent is applied to freshly cut dentin and polymerized before
      making an impression. Interactions are suspected between the resin coating and
      the impression material. PURPOSE: The purpose of this study was to identify
      possible interactions between 2 impression materials and resin-coated tooth
      surfaces using 2 different dentin bonding agents. MATERIAL AND METHODS: Extracted
      molars (n=6) with flat midcoronal preparations underwent 1 of 4 procedures:
      control group, unsealed tooth surface/impression; IDS group, immediate dentin
      sealing (Optibond FL or Clearfil SE Bond)/impression; IDS/AB group, immediate
      dentin sealing/air blocking/impression; IDS/AB-P group, immediate dentin
      sealing/air blocking/pumicing/impression. All specimens underwent impressions
      (Impregum Soft or Extrude). Optical microscopy was used to detect unpolymerized
      and residual impression material on the bonded tooth surface. RESULTS: A
      substantial layer of unpolymerized resin (oxygen-inhibited layer) was found in
      the IDS group, which resulted in100% faulty impressions (unpolymerized impression
      material) for both adhesives and impression materials. Air blocking the resin
      coating (IDS/AB group) did not completely eliminate the oxygen-inhibited layer of
      Optibond FL and slightly altered the surface of SE Bond (wrinkles). Only SE Bond
      along with Extrude generated ideal impressions in group IDS/AB, while all other
      combinations of adhesive/impression material resulted in faulty impressions
      (unpolymerized impression material or adhesions). The IDS/AB-P group yielded
      ideal Extrude impressions but generated faulty Impregum impressions (adhesions)
      in more than 50% of the specimens. CONCLUSIONS: Immediate dentin sealing should
      be followed by air blocking and pumicing to generate ideal impressions with
      Extrude. Impregum is not recommended in combination with immediate dentin
      sealing.

PMID- 19853173
TI  - Delayed setting and hygroscopic linear expansion of three gypsum products used
      for cast articulation.
AB  - STATEMENT OF PROBLEM: Wetting of the set gypsum product used for cast
      articulation may result in additional expansion. PURPOSE: The purpose of this
      study was to evaluate the linear expansion of 2 type II and 1 type III gypsum
      products with and without addition of water after setting, over a time period of
      120 hours. MATERIAL AND METHODS: The gypsum products tested in this study were
      Model Plaster, Lab Plaster, and Mounting Stone. All materials were hand mixed for
      5 seconds and mechanically mixed under vacuum for another 15 seconds. The mixes
      were poured into a linear expansion-measuring instrument (n=20). Half of the
      specimens were wet with 25 ml of water immediately after the setting time
      recommended by the manufacturer, and at all time intervals, immediately after
      data collection. No treatment was performed on the remainder of the specimens.
      The expansion values were recorded with an expansion-measuring device over a
      period of 120 hours. Collected data were subjected to a 2-way repeated-measures
      analysis of variance (ANOVA) (alpha=.05). RESULTS: The highest expansion values
      for all gypsum products were recorded at 96 and 120 hours. No significant
      difference in setting expansion values was recorded between these 2 time
      intervals for any of the materials and treatment conditions (dry vs. wet). Mean
      expansion values ranged between 0.08% +/-0.06% for dry Mounting Stone specimens
      at 15 minutes, to 0.57% +/- 0.02% for wet Lab Plaster specimens at 96 and 120
      hours. Significant differences (P<.001) between different mounting gypsum
      products and time were identified. A significant difference between wet and dry
      specimens was not observed. CONCLUSIONS: The expansion of all gypsum products
      used for articulation purposes was complete at 96 hours. The type III gypsum
      product demonstrated lower mean expansion values than type II products. Time and
      material were more important factors than the dry/wet condition when measuring
      total expansion values. Type II gypsum products demonstrated 80% or more of the
      total expansion values in the first 45 minutes, while type III stone demonstrated
      the same expansion after 24 hours.

PMID- 19853172
TI  - Microtensile bond strength of new self-adhesive luting agents and conventional
      multistep systems.
AB  - STATEMENT OF PROBLEM: Several self-adhesive luting agents have recently been
      introduced on the market. It is crucial to know the effectiveness of such luting
      agents prior to their clinical application. PURPOSE: The purpose of this study
      was to evaluate the microtensile bond strengths (microTBS) produced by different
      self-adhesive cements and compare them with conventional luting agents. MATERIAL
      AND METHODS: Six self-adhesive cements (RelyX Unicem (UN), RelyX U100 (UC),
      SmartCem 2 (SC), G-Cem (GC), Maxcem (MC), and SeT (SET), and 2 conventional
      luting agents, one that uses a 2-step etch-and-rinse adhesive (RelyX ARC (RX)),
      and one that uses a 1-step self-etching adhesive (Panavia F (PF)), were used in
      this study. An additional group included the use of a 2-step self-etching primer
      adhesive system (Clearfil SE Bond) prior to the application of Panavia F (PS).
      Fifty-four human molars were abraded to expose occlusal surfaces and were
      assigned to 9 groups according to the luting material (n=6). Five composite resin
      (Filtek Z250) discs (12 mm in diameter, 5 mm thick) were cemented on the teeth
      according to manufacturers' instructions. After 24 hours of water storage,
      restored teeth were serially sectioned into beams with a cross-sectional area of
      approximately 1 mm2 at the bonded interface and were tested in tension with a
      crosshead speed of 1 mm/min. Failure mode was determined using scanning electron
      microscopy. Data were statistically analyzed by 1-way ANOVA and Tukey's
      studentized range HSD test (alpha =.05). RESULTS: Mean bond strengths (SD) in MPa
      were: RX, 69.6 (16.6)A; PS, 49.2 (9.7)A; PF, 33.7 (13.9)AB; GC, 16.9 (10.3)BC;
      UC, 15.3 (3.4)BC; UN, 12.5 (2.4)C; MC 11.5 (6.8)CD; SC, 8.5 (4.9)CD; SET, 4.6
      (0.5)D. Groups with different uppercase letters were significantly different from
      each other (P<.05). The predominant failure mode of the self-adhesive cements was
      adhesive between the resin cement and dentin. CONCLUSIONS: The bond strengths
      produced by the multistep luting agents were significantly higher than those
      observed for most self-adhesive cements.

PMID- 19853174
TI  - Pressure transmission and distribution under impact load using artificial denture
      teeth made of different materials.
AB  - STATEMENT OF PROBLEM: Pressure transmission and distribution under denture bases
      may be different depending on the material of the artificial denture teeth used.
      PURPOSE: The purposes of this study were to evaluate pressure transmission and
      distribution under impact load using artificial denture teeth composed of
      different materials, and to examine the modulus of elasticity of the artificial
      denture teeth. MATERIAL AND METHODS: The denture base specimens with artificial
      denture teeth made of 4 different materials (acrylic resin, microfilled composite
      resin, nanocomposite resin, and ceramic) were evaluated. Pressure transmission,
      distribution, and maximum pressure (n=10) were observed with pressure-sensitive
      sheets under an impact load. Modulus of elasticity of the artificial denture
      teeth (n=10) was measured by using an ultramicroindentation system. Data were
      statistically analyzed with 1-way ANOVA, followed by Tukey HSD and Tamhane's
      multiple range post hoc tests (alpha=.05). RESULTS: Maximum pressure transmission
      observed from ceramic denture teeth was significantly higher than that of other
      groups (P<.001). Nanocomposite resin denture teeth presented the lowest pressure
      transmission, whereas a localized stress transmission area was observed in the
      ceramic denture teeth group. Significant differences in the modulus of elasticity
      were observed among the 4 types of artificial denture teeth (P<.001).
      CONCLUSIONS: Pressure transmission and distribution varied among the denture
      tooth materials. Differences in the modulus of elasticity of each type of denture
      tooth were demonstrated.

PMID- 19853175
TI  - Further experience with modification of an intraluminal button for hands-free
      tracheoesophageal speech after laryngectomy.
AB  - Tracheoesophageal (TE) speech using a voice prosthesis and hands-free speaking
      valve with an intraluminal attachment is the gold standard for voice restoration
      after total laryngectomy. Modification of a standard self-retaining silicone
      cannula or laryngectomy button often aids in the attachment of a speaking valve
      within the tracheal lumen for hands-free TE speech production. An increased
      number of laryngectomized individuals are able to achieve hands-free TE speech
      when the standard length, flange, and diameter of a silicone button is customized
      to accommodate individual tracheostomal contours. A technique is presented for
      modification of a standard silicone laryngectomy button to facilitate hands-free
      TE speech after total laryngectomy.

PMID- 19853176
TI  - Fabricating a cast for denture tooth repair.

PMID- 19853177
TI  - ICRP publication 109. Application of the Commission's Recommendations for the
      protection of people in emergency exposure situations.
AB  - This report was prepared to provide advice on the application of the Commission's
      2007 Recommendations. The advice includes the preparedness for, and response to,
      all radiation emergency exposure situations defined as: 'situations that may
      occur during the operation of a planned situation, or from a malicious act, or
      from any other unexpected situation and require urgent action in order to avoid
      or reduce undesirable consequences'. An emergency exposure situation may evolve,
      in time, into an existing exposure situation. The Commission's advice for these
      types of situation is published in two complementary documents (that for
      emergency exposure situations in this report, that for existing exposure
      situations following emergency exposure situations in a forthcoming report
      entitled 'Application of the Commission's recommendations to the protection of
      individuals living in long-term contaminated territories after a nuclear accident
      or a radiation emergency'). The Commission's 2007 Recommendations re-state its
      principles of justification and optimisation, and the requirement to protect
      against severe deterministic injury, as applying to emergency exposure
      situations. For the purpose of protection, reference levels for emergency
      exposure situations should be set in the band of 20-100 mSv effective dose (acute
      or per year). The reference level represents the level of residual dose or risk
      above which it is generally judged to be inappropriate to plan to allow exposures
      to occur. The Commission considers that a dose rising towards 100 mSv will almost
      always justify protective measures. Protection against all exposures, above or
      below the reference level, should be optimised. More complete protection is
      offered by simultaneously considering all exposure pathways and all relevant
      protection options when deciding on the optimum course of action in the context
      of an overall protection strategy. Such an overall protection strategy must be
      justified, resulting in more good than harm. In order to optimise an overall
      strategy, it is necessary to identify the dominant exposure pathways, the time
      scales over which components of the dose will be received, and the potential
      effectiveness of individual protective options. If, in application of an overall
      protection strategy, protection measures do not achieve their planned residual
      dose objectives, or worse, result in exposures exceeding reference levels defined
      at the planning stage, a re-assessment of the situation is warranted. In planning
      and in the event of an emergency, decisions to terminate protective measures
      should have due regard for the appropriate reference level. The change from an
      emergency exposure situation to an existing exposure situation will be based on a
      decision by the authority responsible for the overall response. This transition
      may happen at any time during an emergency exposure situation, and may take place
      at different geographical locations at different times. The transfer should be
      undertaken in a co-ordinated and fully transparent manner, and should be
      understood by all parties involved.

PMID- 19853181
TI  - Preface.

PMID- 19853182
TI  - HPV-related carcinogenesis: basic concepts, viral types and variants.
AB  - Human papillomavirus (HPV) constitutes a diverse group of small DNA virus, some
      extensively studied during the last three decades due to their carcinogenic
      potential. Persistence of viral infections and uncontrolled expression of E6 and
      E7 viral oncogenes are critical events in transformation. A surprisingly large
      number of different HPV types have been identified and classified (>100) and it
      has been anticipated that almost 200 may exist. HPV types are thought to have
      originated very early during human evolution and are now defined by their L1
      genomic sequence, differing by >10% among them. Importantly, viral types are cell
      type specific and usually produce different kinds of lesions, benign or
      malignant. In addition, these types have co-evolved with their hosts and have
      generated what we call now intratype variants. Variants of HPV types are found
      associated with the ethnicity of the populations and have been grouped
      geographically. It is believed that HPV intratype variants may differ in
      biological behavior. Recognition of the crucial role that some specific HPV types
      play in cervical cancer development is highly important for their prevention and
      implementation of public health strategies to control cervical cancer, still the
      leading cause of death among cancer patients in many developing nations. Here we
      review basic concepts of HPV-induced carcinogenesis and molecular differences
      found among HPV types and intratype variants and discuss their clinical and
      functional implications.

PMID- 19853183
TI  - Host factors in HPV-related carcinogenesis: cellular mechanisms controlling HPV
      infections.

PMID- 19853184
TI  - Immunobiology of HPV Infection.

PMID- 19853185
TI  - The role of retinoid deficiency and estrogens as cofactors in cervical cancer.
AB  - Persistent infection with high-risk human papillomaviruses (HR-HPVs) is involved
      in cervical cancer (CC), a major cause of cancer mortality worldwide. Infection
      occurs primarily at the transformation zone (TZ), the most estrogen- and retinoid
      sensitive region of the cervix. Development of CC affects a small percentage of
      HR-HPV-infected women and often takes decades after infection, suggesting that HR
      HPV is a necessary but not sufficient cause of CC. Thus, other cofactors are
      necessary for progression from cervical HR-HPV infection to cancer such as long
      term use of hormonal contraceptives, multiparity, smoking, as well as
      micronutrient depletion and in particular retinoid deficiency, which alters
      epithelial differentiation, cellular growth and apoptosis of malignant cells.
      Therefore, early detection of HR-HPV and management of precancerous lesions
      together with a profound understanding of additional risk factors could be a
      strategy to avoid this disease. In this review we focus on the synergic effect of
      estrogens, retinoid deficiency and HR-HPVs in the development of CC. These risk
      factors may act in concert to induce neoplastic transformation in squamous
      epithelium of the cervix, setting the stage for secondary genetic or epigenetic
      events leading to cervical cancer.

PMID- 19853186
TI  - HPV vaccines: preclinical development.
AB  - The knowledge about immune biology of human papillomaviruses stems mainly from
      animal models that also formed the basis for establishing the strategy for the
      current vaccines. They consist of virus-like particles (VLP) that are DNA-free
      virus particles composed of 360 molecules of the major structural protein L1.
      Protection against virus infection depends upon neutralizing antibodies that
      prevent the interaction between the virus and its host cell, i.e., the
      keratinocyte at the basal layer of the epithelium. Despite the good performance
      of the current vaccines (prevention of infection with the high-risk HPV types 16
      and 18 and the anogenital lesions induced by them), development of second
      generation product(s) is mandatory, in particular in view of the medical need in
      areas of the highest burden of cervical cancer.

PMID- 19853187
TI  - Advantages and disadvantages of current prophylactic vaccines against HPV.
AB  - Persistent infections with human papillomavirus (HPV) types of the alpha
      papillomavirus genus that form the so-called high-risk (HR) group constitute the
      major risk for developing cancer of the uterine cervix, with nearly 500,000 new
      cases every year worldwide and approximately 250,000 deaths. Infections with low
      risk (LR) types are usually associated with development of genital warts.
      Asymptomatic infections with both HR and LR types constitute the leading sexually
      transmitted disease, with approximately 8-12% of all sexually active women
      infected at a given time. Two commercial vaccines against HPV (Gardasil and
      Cervarix) are currently in the market in many countries worldwide. Both are
      produced with recombinant technologies, consist of self-assembled virus-like
      particles, the so-called VLPs, and have shown high immunogenicity. More
      important, they have been found to be highly efficient in preventing persistent
      infections and lesions not only from the uterine cervix, but also from the anus,
      vagina, and vulva. Unfortunately, vaccines are very expensive and unaffordable
      for many public health initiatives in developing countries. They include two
      types involved in cancer development (types 16 and 18); therefore, we can only
      expect a partial protection against cancer (70/100), making it necessary to
      implement novel strategies to detect precursor lesions and cancer in the
      postvaccine era. Strategies that include education and organized screening
      programs with detection of persistent infections should be implemented in
      developing countries if a reduction of cancer of the uterine cervix is expected
      over the next years.

PMID- 19853188
TI  - The expected impact of HPV vaccination on the accuracy of cervical cancer
      screening: the need for a paradigm change.
AB  - We used modeling approaches to estimate the impact of human papillomavirus (HPV)
      vaccination on the performance of Pap cytology screening under different
      assumptions of lesion prevalence and expected changes in sensitivity and
      specificity likely to prevail post-vaccination. A major driver of the efficiency
      and costs of screening, the positive predictive value will be severely affected
      if Pap cytology continues to serve as the primary screening test in the post
      vaccination era. Molecular-based screening with an HPV DNA test followed by Pap
      triage of HPV-positive cases has the potential for circumventing this problem. As
      a primary screening test, HPV testing can improve the overall quality of
      screening programs, thus allowing for increased testing intervals that would
      lower program costs with acceptable safety. Cytology should be reserved for the
      more labor-efficient task of triaging HPV-positive cases, a situation in which
      case loads would be "enriched" with smears containing relevant abnormalities. HPV
      followed by Pap strategy can also serve a secondary role in post-vaccination
      surveillance.

PMID- 19853189
TI  - Innovation in cervical cancer prevention and control in Mexico.
AB  - Disparities related to cervical cancer continue to exist in Mexico, including
      insufficient screening coverage, problems with quality control and a resulting
      greater risk of mortality among women from marginalized areas. A lack of
      opportunities and requirements for continuing education and accreditation of
      healthcare personnel involved in the screening program is also an issue. HPV DNA
      testing and HPV vaccines are recent technological innovations that offer a
      potential solution to the continued negative impact of cervical cancer among
      Mexican women. This essay attempts to answer questions such as: Why should HPV
      testing be integrated into the early detection program in Mexico? How can HPV
      testing best be integrated into the program in Mexico? How-from a public health
      perspective that seeks to reduce disparities-can HPV vaccination best be
      implemented in Mexico? HPV testing allows increased positive predictive value
      while also reducing costly and unnecessary overtreatment of low-grade
      abnormalities, and HPV vaccines offer the possibility of primary prevention of
      cervical cancer. The strategy proposed for Mexico includes primary prevention
      with HPV vaccination for girls aged between 12 and 16 years (before sexual
      initiation), Pap testing with excellent quality control for women 24-34 years of
      age and high-risk HPV DNA testing for women 35 years and older. HPV samples would
      be either clinically collected or self-collected and women with positive HPV test
      results would receive follow-up high-quality Pap testing. This approach is
      creative and focuses on reducing disparities and providing high-quality care that
      is also cost effective.

PMID- 19853190
TI  - The therapeutic vaccine: is it feasible?
AB  - In contrast to the prophylactic HPV vaccines that exhibit great promise in
      reducing the burden of cervical cancer, there is limited progress towards the
      development of immune therapeutic strategies that would help those women who are
      already infected with high-risk HPV and do not benefit from the current vaccines.
      The reason for this drawback is the lack of knowledge about the immune mechanisms
      that control the growth of HPV-infected or -transformed cells in vivo. It became
      evident that the preclinical models in rodents provide only limited information
      about the performance of a candidate vaccine in humans. In particular, the immune
      correlate for a clinical response remains to be determined. On the other hand,
      HPV-related malignancies provide an excellent model for cancer immune therapies
      in general. There is hope that the continuous efforts of academic research
      combined with corporate involvement will finally present an efficient product.

PMID- 19853191
TI  - Ethical dilemmas and great expectations for human papilloma virus vaccination.
AB  - When the first preventive HPV vaccine became available in 2006, it drew both
      enthusiasm and multiple ethical problems. In the case of HPV vaccination, there
      is a clear conflict between the scientific data that claim a definitive advantage
      for preventing HPV infection in the exposed population and the ethical and moral
      issues resulting from a compulsory program. Despite the evident success of
      routine and compulsory vaccination in young women, there is increasing concern
      about safety, efficacy, and equity of the vaccine and to close the knowledge
      "gaps" about HPV infection and consequent health outcomes. Some of these fears
      are expressed particularly in conservative groups that link these arguments to
      those of religious and moral issues contending that HPV vaccination is an
      indirect license for liberal sexual activity in youths, resulting in promiscuity
      and/or less participation in cervical cancer screening. It has been well
      demonstrated that HPV infection can lead to harm through the induction of
      premalignant and cancerous lesions. Therefore, any proven method for preventing
      infection, such as HPV vaccines, should be used in persons at risk. These
      policies, however, should be strictly linked to cervical cancer screening
      programs.

PMID- 19853192
TI  - Cost-effectiveness analysis of a quadrivalent human papilloma virus vaccine in
      Mexico.
AB  - BACKGROUND AND AIMS: Cervical cancer is one of the main causes of death in women
      in low- and middle-income countries. Despite technological and scientific
      advances that allow an early detection of precancerous lesions and curative
      treatment of cervical cancer, Mexico and other Latin American countries have only
      been able to obtain a small decrease in the mortality rates for this kind of
      cancer. How to implement and sustain effective public health strategies for
      cervical cancer prevention, such as increasing cytology-based screening program
      coverage and implementing HPV-DNA testing and vaccination, are important
      questions. The aim of this study is to perform a cost-effectiveness analysis of
      the introduction of a quadrivalent (HPV 6/11/16/18) HPV vaccine into the public
      health system and evaluate the epidemiological and economic benefits on
      prevention of cervical cancer in Mexico. METHODS: A Markov model is used to
      simulate the natural history of HPV infection in a cohort of Mexican women to
      evaluate the cost-effectiveness of the cervical cancer screening strategy used in
      Mexico as well as the benefits of other potential strategies such as 1)
      vaccination only, 2) conventional cytology-based screening program only and 3)
      vaccination followed by screening. For the strategies that involve screening we
      have chosen screening intervals of 3 and 5 years. The model produces results that
      are reasonably close to the epidemiological data related to HPV and cervical
      cancer in Mexico. RESULTS: The quadrivalent HPV vaccine could reduce the
      probability of persistent HPV-16/18 infection by at least 60%, which would result
      in a near-proportional reduction in HPV-16/18-associated invasive cervical cancer
      and CIN 3. CONCLUSIONS: The strategy of using only vaccination ($45 USD for three
      doses) as a preventive measure was a very cost-effective strategy in Mexico
      ($68USD/LYS). The strategy of vaccination with traditional screening of Pap test
      every 3 years produced higher cost by a lower performance of cervical cytology in
      Mexico, at a cost of $15,935 USD per life-year. The cost-effectiveness of the
      vaccination strategy was highly sensitive to age of vaccination, duration of
      vaccine efficacy, and cost of vaccination. The Mexican model predicts that a
      quadrivalent HPV vaccine will reduce the incidence of high- and low-risk
      associated cervical cancer. A program of vaccination as a preventive strategy is
      likely cost effective. The results of this study could be of great value in
      decision-making for the implementation of an HPV vaccine as a public health
      policy in Mexico provided that the cost of each dose will be, at most, $15
      dollars (USD) dollars, combined with HPV testing, the new strategy of national
      secondary prevention program.

PMID- 19853193
TI  - Impact of a quadrivalent HPV6/11/16/18 vaccine in Mexican women: public health
      implications for the region.
AB  - BACKGROUND AND AIMS: Recognition of human papillomavirus (HPV) as a necessary
      cause of cervical cancer (CC) led to new perspectives for its control and the
      demonstration of an effective primary prevention strategy through vaccination. We
      undertook this study to evaluate the safety, efficacy and immunogenicity of a
      quadrivalent HPV6/11/16/18 vaccine in Mexican women. METHODS: A total of 679
      Mexican women between 18 and 23 years old participated in two Phase III double
      blind, randomized, placebo-controlled clinical trials of a quadrivalent HPV
      6/11/16/18 vaccine. Women were enrolled who tested negative for pregnancy and
      reported having four or less sexual partners during their lifetime. Vaccine or
      placebo was administered at day 1, month 2 and month 6. RESULTS: Among Mexican
      women who were naive to the respective vaccine type at enrollment, the
      quadrivalent vaccine was highly efficacious, preventing 100% of HPV6/11/16/18
      related cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ,
      condyloma and vaginal intraepithelial neoplasia. Statistical significance was not
      reached for every endpoint due to the limited sample size. Vaccination was
      generally well tolerated and immunogenic. DISCUSSION: To widely administer the
      vaccine, collaborative efforts should be coordinated among public, private and
      local community sectors. In light of the scarce knowledge of many health
      professionals with respect to the primary prevention of CC, it will be necessary
      to educate health providers on the advantages and specific recommendations of HPV
      vaccines and secondary prevention. Decision making should be based on scientific
      evidence, allowing health professionals to provide an organized social response
      that supports the universal right to health.

PMID- 19853194
TI  - Doctors without metaphors.

PMID- 19853195
TI  - Quiz Page November 2009. Refractory hypertension in a man undergoing long-term
      hemodialysis: renovascular hypertension secondary to left renal arteriovenous
      malformation.

PMID- 19853197
TI  - p-Cresol sulfate: further understanding of its cardiovascular disease potential
      in CKD.

PMID- 19853196
TI  - Peridialytic, intradialytic, and interdialytic blood pressure measurement in
      hemodialysis patients.

PMID- 19853198
TI  - Solute-solver: a web-based tool for modeling urea kinetics for a broad range of
      hemodialysis schedules in multiple patients.
AB  - Practical application of urea kinetic modeling to measure the delivered dose of
      hemodialysis is hampered by lack of a reference or gold-standard program that
      would be widely available and freely distributed. We developed and here describe
      an open-source JavaScript tool, "Solute-Solver," capable of batch processing of
      urea kinetics calculations. The Solute-Solver online interface is available at
      (www.ureakinetics.org); in addition, the tool can be used as a standalone HTML
      file that is designed to be run using a web browser. Solute-Solver is written in
      uncompiled JavaScript for transparency and easy modification, and the source code
      is available for download and modification. The program uses fourth-order Runge
      Kutta numerical integration applied to a variable-extracellular-volume 2-pool
      model to compute a variety of clearance measures, including 1-pool and 2-pool
      Kt/V, "standard" weekly Kt/V, and other equivalent clearance measures. The
      program accepts comma- or semicolon-delimited input (which can be produced from a
      spreadsheet) and generates a separator-delimited output file that can be imported
      back into a spreadsheet or other database. The program also produces individual
      patient-by-patient report pages. It typically provides kinetic output for 300
      patient treatments in 30-60 seconds. Advantages of this program over previously
      available equations and algorithms include the capacity to properly model such
      newer dialysis schedules as 6-times-weekly short daily or nocturnal hemodialysis,
      as well as account for substantial variation in residual renal function.
      Ultimately, this effort may promote wider use of formal urea modeling and
      facilitate research that requires measurement of hemodialysis or hemodialysis
      adequacy, especially involving the newer expressions of continuous equivalent
      clearance, and expressions of clearance normalized to body surface area.

PMID- 19853199
TI  - Hepcidin levels in acute kidney injury following cardiopulmonary bypass grafting.

PMID- 19853201
TI  - Evidence of occult hepatitis C virus infection in hemodialysis patients.

PMID- 19853202
TI  - Intramuscular or intradermal hepatitis B vaccine administration in hemodialysis
      patients?

PMID- 19853205
TI  - Estimated GFR for drug dosing: a bedside formula.

PMID- 19853206
TI  - Drug dose adjustments in patients with renal impairment.

PMID- 19853207
TI  - Estimated GFR vs creatinine clearance for drug dosing.

PMID- 19853208
TI  - Use of the MDRD study equation for drug dosing.

PMID- 19853210
TI  - Fluid infusion during CPR and after ROSC--is it safe?

PMID- 19853211
TI  - Epilepsy. Preface.

PMID- 19853212
TI  - Determinants of quality of life in people with epilepsy.
AB  - This article reviews evidence of quality of life (QOL) determinants in people
      affected by epilepsy, including detractors and promoters. Emerging factors of
      particular significance for QOL are highlighted, including seizure frequency,
      medication side effects, psychological comorbidity, and stigma and
      discrimination. This article also examines the role of resilience, interpreted in
      its widest sense, for promoting good QOL, even in the presence of poorly
      controlled seizures. The importance of addressing both clinical and wider
      psychosocial issues is highlighted and some possible directions for future
      research into QOL in epilepsy are suggested.

PMID- 19853213
TI  - Depression and epilepsy: a review of multiple facets of their close relation.
AB  - Depressive disorders are the most frequent comorbidity of PWE. As discussed in
      this article, the depressive disorder is another expression of a neurologic
      disorder with psychiatric symptoms. The high comorbidity of both conditions can
      be explained by the existence of common pathogenic mechanisms whereby one
      condition facilitates the occurrence of the other. The negative impact of
      depressive disorders in the life of PWE is significant; hence, a prompt
      recognition should be followed by a treatment designed to yield complete symptom
      remission.

PMID- 19853215
TI  - The etiology of psychogenic non-epileptic seizures: toward a biopsychosocial
      model.
AB  - Psychogenic non-epileptic seizures (PNES) are one of the most common differential
      diagnoses of epilepsy. PNES are poorly understood and often sub-optimally
      treated. This article summarizes current knowledge about the etiology of PNES.
      Through describing the interactions of predisposing, precipitating, perpetuating,
      and triggering factors, an integrated biopsychosocial model of a complex disorder
      is developed. PNES emerge as a dissociative response to a range of different
      stressors in vulnerable individuals. Once established, maintaining factors turn a
      temporary disturbance into a chronically disabling disorder.

PMID- 19853216
TI  - Predicting seizures: a behavioral approach.
AB  - This article reviews the epilepsy cycle, distinguishing the interictal, preictal,
      ictal, and postictal phases. Evidence suggesting that the preictal phase can
      sometimes be identified based on neurophysiologic signals, premonitory features,
      the presence of trigger factors, or self-report is also reviewed. Diary studies
      have shown that seizures are not randomly distributed in time and that a subgroup
      of persons with epilepsy can predict an impending seizure. Paper diary data and
      preliminary analysis of electronic diary data suggest that seizure prediction is
      feasible. Whereas all of this evidence sets the stage for seizure prediction and
      preemptive therapy, several questions remain unanswered. First, what proportion
      of persons with epilepsy can predict their seizures? Second, within and among
      individuals, how accurate is prediction? Third, can prediction be improved
      through education about group level or individual predictors? And finally, in a
      group that can make robust predictions what are the most effective interventions
      for reducing seizure probability at times of high risk? The answers to these
      questions could reduce the burden of epilepsy by making seizures predictable and
      setting the stage for preemptive therapy. This work could improve the
      understanding of epilepsy by providing a context for studying the transitions
      from the interictal to preictal and ictal states. More prospective studies are
      needed; challenges certainly exist, but as the studies discussed here
      demonstrate, the field is rich with promise for improving the lives of patients
      with epilepsy.

PMID- 19853214
TI  - The emerging architecture of neuropsychological impairment in epilepsy.
AB  - A new literature is now under way, one linking cognitive abnormalities directly
      to indices of structural, functional, metabolic, and other neurobiologic markers
      of cerebral integrity, independent of their association with clinical epilepsy
      characteristics. These trends are reviewed in this article. The focus is on
      temporal lobe epilepsy (TLE) as a model with which to address the core points
      because this form of localization-related epilepsy has been very carefully
      studied from both a cognitive and imaging standpoint. Some pertinent historical
      issues are touched on first, followed by more detailed reviews of the cognitive
      and neuroimaging abnormalities that have been found in TLE, followed by an
      overview of studies examining direct structure-function relationships in TLE and
      other epilepsies.

PMID- 19853218
TI  - Selection of antiepileptic drugs in adults.
AB  - Epilepsy affects approximately 50 million people worldwide, with an annual
      incidence of 50 to 70 cases per 100,000 population. The condition can strike at
      any time of life, with an immediate impact on everyday activities and routine.
      Key to optimal management is swift referral to an epilepsy specialist,
      appropriate investigation, and timely institution of antiepileptic drug therapy.
      In the past 20 years, the explosion of 13 new agents into the marketplace has
      greatly increased the potential for therapeutic intervention. This article
      explores the rationale for treatment selection in adults with epilepsy.

PMID- 19853217
TI  - Hormonal aspects of epilepsy.
AB  - The relationships among hormones, epilepsy, and the medications used to treat
      epilepsy are complex, with tridirectional interactions that affect both men and
      women in various ways. Abnormalities of baseline endocrine status occur more
      commonly in people with epilepsy. Abnormalities are most often described for the
      sex steroid hormone axis, commonly presenting as sexual dysfunction in men and
      women with epilepsy and lower fertility. Other signs and symptoms in women with
      epilepsy include menstrual irregularities, premature menopause, and polycystic
      ovarian syndrome. The evaluation and care of adult patients with epilepsy should
      include considerations of the common hormonal aberrations that occur in this
      patient population. Questions about reproductive health disorders, sexual
      function, symptoms of thyroid disorders, and bone health should be part of the
      evaluation of all adult patients with epilepsy. Further laboratory or radiologic
      testing and referral to other specialists to participate in collaborative care
      may be warranted if underlying disorders are suspected, especially given that
      many of these hormone abnormalities can result in long-term health risks as well
      as negatively affect quality of life. AEDs and hormones have a bidirectional
      interaction that can impair the efficacy of contraceptive hormone treatments and
      of the AEDs. Endogenous hormones can influence seizure severity and frequency,
      resulting in catamenial patterns of epilepsy. However, this susceptibility to
      hormonal influences can be used to develop hormonal strategies to improve seizure
      control in women with epilepsy with use of cyclic PROG supplementation or
      alteration of the endogenous hormone release. Additionally, development of the
      neurosteroid analog ganaxolone provides a novel approach that can potentially be
      used across both genders and all age groups.

PMID- 19853219
TI  - Teratogenic effects of antiepileptic medications.
AB  - Data on clinical teratogenicity are at best derived from carefully conducted
      observational studies, whereas randomized, controlled trials have no place in
      this research area. We can only expect level B recommendations and lower. New
      relevant information has become available during the last 5 years on pregnancy
      outcomes with 3 of the most frequently used AEDs: carbamazepine, valproate, and
      lamotrigine. It seems that birth defect rates with arbamazepine monotherapy are
      lower than previously thought. In some large studies rates are only marginally
      increased compared with different control populations. More recent data do not
      suggest adverse effects of carbamazepine on cognitive development. The overall
      prevalence of malformations in association with lamotrigine exposure seems to be
      similar to that of carbamazepine. The only available prospective study on
      cognition does not indicate any adverse effects of lamotrigine. Malformation
      rates with valproate have consistently been found to be 2 to 3 times higher
      compared with carbamazepine or lamotrigine. More limited data also suggest
      adverse effects of high doses of valproate on cognitive development of the
      exposed child. For newer generation AEDs other than lamotrigine, data are still
      too limited to determine the risks for birth defects and are nonexisting with
      respect to possible adverse effects on cognitive development. Doses are
      important, and evidence is lacking for higher risks with valproate compared with
      other AEDs if doses are less than 800 to 1000 mg/d. Confounding factors
      contribute to some of the apparent differences between AEDs in pregnancy
      outcomes, and more data are needed, particularly concerning cognitive outcomes
      and specific birth defects. Based on these observations, valproate should not be
      a first-line AED for women who are considering pregnancy. In this situation this
      drug is best avoided if other effective but safer AEDs can be found for each
      individual woman's seizure disorder. Based on pregnancy outcome data,
      carbamazepine seems comparatively safe and a reasonable first-line choice in
      localization-related epilepsy. Alternatives are less clear in idiopathic
      generalized epilepsies. Lamotrigine seems comparatively safe, but its use in
      pregnancy is complicated by pharmacokinetic changes and risks of breakthrough
      seizures. The experience with use of levetiracetam and topiramate during
      pregnancy is still insufficient. Any attempt to change drugs should be completed
      and evaluated before conception; withdrawals or other major changes should be
      avoided during pregnancy. These conclusions are largely in line with the recently
      published report of the Quality Standards Subcommittee and Therapeutics and
      Technology Subcommittee of the American Academy of Neurology and the American
      Epilepsy Society.

PMID- 19853220
TI  - Identification of pharmacoresistant epilepsy.
AB  - There is no single definition of pharmacoresistant (intractable, refractory)
      epilepsy. Prospective identification of pharmacoresistance is complicated by the
      variability of its appearance across different types of epilepsy and the
      variability of seizure control within a given patient over time. Failure of
      informative trials of two appropriate antiepileptic drugs has been recommended as
      a threshold that should trigger referral for evaluation at a comprehensive
      epilepsy center. Maximizing seizure control is imperative for reducing the risks
      and consequences of epilepsy, including the cognitive and psychiatric
      comorbidities and even sudden death.

PMID- 19853221
TI  - Localization in epilepsy.
AB  - Pharmacologic therapy represents the first line of treatment of epilepsy and is
      effective in most patients. However, about 20% to 30% of cases develop
      intractable seizures that cannot be controlled by medication alone. In such
      cases, surgical intervention is considered for therapeutic, often curative
      purposes. Dynamic spatiotemporal variability in the epileptic focus renders
      seizure localization a challenge to the clinician. Many diagnostic modalities
      have been developed to identify different aspects of the epileptic focus. Older
      techniques are being increasingly supplemented by a variety of anatomic and
      functional imaging modalities that can help clarify discrepancies. Invasive
      electroencephalography remains the gold standard for identifying epileptic foci
      and guiding the surgeon to successful resections.

PMID- 19853222
TI  - Therapeutic brain stimulation for epilepsy.
AB  - DBS has been a possible therapy for epilepsy for more than 30 years, and now it
      is moving to the point of clinical utility. Animal models have shown efficacy of
      DBS at several brain regions, although not all animal studies have shown
      efficacy. Clinically, an array of sites have been explored, including the
      cerebellum, anterior nucleus of the thalamus, CM nucleus, hippocampus,
      subthalamic nucleus, brainstem, and corpus callosum; direct stimulation of the
      cortex has also been explored. Interest in evaluating these sites for treatment
      of epilepsy has been enhanced by the success of vagus nerve stimulation for
      epilepsy and DBS for movement disorders. Literature consists of mostly small and
      uncontrolled studies that are subject to limitations in interpretation. A pivotal
      large, double-blind controlled trial of anterior nucleus of the thalamus has
      recently been completed, and it showed efficacy for partial seizures with or
      without secondary generalization.28 A controlled trial for RNS is underway.57 In
      addition, pilot studies of hippocampal stimulation 41,43 are expected to lead to
      more definitive trials of this site.Brain stimulation for epilepsy holds several
      challenges for the future. Mechanisms of DBS are poorly understood, although
      investigations are actively being pursued. Little is known about optimal
      stimulation parameters. DBS has been little examined in cases of intractable
      generalized epilepsy. Because DBS carries some risk, mainly of hemorrhage and
      infection, clinicians will need to develop an effective method of identifying the
      best candidates. DBS is palliative rather than curative, but experience suggests
      that this relatively new therapy may be of benefit to some people with otherwise
      untreatable epilepsy.

PMID- 19853223
TI  - Advances on the genetics of mendelian idiopathic epilepsies.
AB  - Genetic factors play an increasingly recognized role in idiopathic epilepsies.
      Since 1995, positional cloning strategies in multi-generational families with
      autosomal dominant transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4,
      CHRNA2, CHRNB2, SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGI1) and numerous loci
      for febrile seizures and epilepsies. To date, all genes with the exception of
      LGI1 (leucine-rich glioma inactivated 1), encode neuronal ion channel or
      neurotransmitter receptor subunits. Molecular approaches have revealed great
      genetic heterogeneity, with the vast majority of genes remaining to be
      identified. One of the major challenges is now to understand phenotype-genotype
      correlations. This review focuses on the current knowledge on the molecular basis
      of these rare Mendelian autosomal dominant forms of idiopathic epilepsies.

PMID- 19853224
TI  - Sudden unexpected death in epilepsy (SUDEP): update and reflections.
AB  - SUDEP remains a significant clinical problem, which, in the authors' opinion, is
      to some extent potentially preventable. Research needs to focus on interventions
      that may alter risk. Some wide-ranging suggestions for future developments that
      in time can translate to clinical practice have been presented. These
      suggestions, the authors believe, give rise to cautious optimism.

PMID- 19853225
TI  - Introduction.

PMID- 19853226
TI  - Acute gastrointestinal hemorrhage.
AB  - Although most cases of acute gastrointestinal (GI) hemorrhage either
      spontaneously resolve or respond to medical management and/or endoscopic
      treatment, there remain a significant number of patients who require emergency
      evaluation and treatment by the interventional radiologist. Any angiographic
      evaluation should begin with selective catheterization of the artery supplying
      the most likely site of bleeding, as determined by the available clinical,
      endoscopic, and imaging data. If a source of hemorrhage is identified,
      superselective catheterization followed by transcatheter embolization with
      microcoils is the most effective means of successfully controlling hemorrhage
      while minimizing potential complications. This is now well-recognized as a viable
      and safe alternative to emergency surgery. In selected situations transcatheter
      intra-arterial infusion of vasopressin may also be useful in controlling acute GI
      bleeding. One must be aware of the various side effects and potential
      complications associated with this treatment, however, and recognize the high
      rebleeding rate. In this article, we review the current role of angiography,
      transcatheter arterial embolization, and infusion therapy in the evaluation and
      management of GI hemorrhage.

PMID- 19853227
TI  - Transjugular intrahepatic portosystemic shunt for acute variceal hemorrhage.
AB  - Acute variceal hemorrhage is life-threatening and requires a multidisciplinary
      approach for effective therapy. Transfusion of blood products, systemic therapy
      with vasopressin, octreotide, and selective beta-blockers and early endoscopic
      therapy are often effective; however, uncontrollable variceal hemorrhage is best
      treated with transjugular intrahepatic porto-systemic shunt (TIPS) creation. This
      procedure involves establishment of a direct pathway between the hepatic veins
      and the portal veins to decompress the portal venous hypertension that is the
      source of the patient's hemorrhage. The procedure is technically challenging,
      especially in critically ill patients, and has a mortality of 30%-50% in the
      emergency setting, but has greater than 90% effectiveness in controlling bleeding
      from gastroesophageal varices. In this review, we discuss the technical aspects
      of TIPS and briefly examine the results of TIPS in managing acute variceal
      hemorrhage.

PMID- 19853228
TI  - Evaluation and management of acute vascular trauma.
AB  - With the technical advances and the increasing availability of sophisticated
      imaging equipment, techniques, and protocols, and with continually evolving
      transcatheter endovascular therapies, minimally invasive imaging and treatment
      options are being routinely used for the clinical management of trauma patients.
      Thus, the primary treatment algorithm for managing acute vascular trauma now
      increasingly involves the interventional radiologist or other endovascular
      specialist. Endovascular techniques represent an attractive option for both
      stabilizing and definitively treating patients who have sustained significant
      trauma, with resultant vascular injury. Endovascular treatment frequently offers
      the benefit of a focused definitive therapy, even in the presence of massive
      hemorrhage that allows for preservation of major vessels or injured solid organs
      and serves as an alternative to an open surgical intervention. This article
      presents an overview of various endovascular techniques that can be used for
      trauma patients presenting with vascular injuries.

PMID- 19853229
TI  - Acute limb ischemia.
AB  - Acute limb ischemia occurs when there is an abrupt interruption of blood flow to
      an extremity usually because of either embolic or thrombotic vascular occlusion.
      When profound ischemia ensues, this represents an emergency in which restoration
      of perfusion through early intervention can lead to limb salvage, whereas delay
      may result in significant morbidity, including limb loss and, potentially, death.
      Patients in whom urgent or semi-urgent surgical or endovascular revascularization
      is indicated may undergo catheter angiography unless there is a contraindication,
      such as profound critical limb ischemia, renal dysfunction, or contrast allergy.
      Alternative imaging modalities include ultrasound, contrast-enhanced computed
      tomographic angiography, and magnetic resonance angiography. The clinical degree
      of the ischemic insult will determine the most appropriate course of management,
      as severely ischemic limbs may require immediate surgical revascularization,
      while endovascular interventions, such as catheter-directed thrombolysis, may be
      appropriate in patients with moderate ischemia. Additionally, many percutaneous
      mechanical thrombectomy devices are being used or undergoing clinical evaluation,
      either alone or in combination with pharmacologic thrombolysis, for the treatment
      of acute limb-threatening ischemia. In this article, we present our approach to
      an acutely ischemic limb, with a focus on the pertinent aspects of endovascular
      intervention.

PMID- 19853230
TI  - Bronchial artery embolization.
AB  - Massive hemoptysis is a life-threatening emergency. Chest radiograph, computed
      tomography, and bronchoscopy play a complementary role in diagnosing the
      underlying cause of hemorrhage and localizing the bleeding site. Bronchial artery
      embolization remains the primary and most effective method in controlling massive
      hemoptysis. Bronchial and nonbronchial systemic arteries are the main source of
      bleeding and are embolized with polyvinyl alcohol particles or gelatin sponge.
      Immediate cessation of bleeding occurs in more than 75% of patients; however,
      long-term recurrences are common in patients with progressive lung disease.
      Complications are infrequent except for a rare occurrence of spinal cord
      ischemia.

PMID- 19853231
TI  - Transcatheter endovascular techniques for management of obstetrical and
      gynecologic emergencies.
AB  - Since the initial description of selective uterine artery embolization for the
      treatment of postpartum hemorrhage in 1979, transcatheter embolization and other
      endovascular techniques have become the second-line therapeutic option for the
      management of intractable obstetrical and gynecologic bleeding. Advances in
      catheter-based techniques, as well as recognition of the effectiveness of
      minimally invasive treatment options, have expanded the role of interventional
      radiology in the management of hemorrhage for a variety of indications, such as
      postpartum hemorrhage, menorrhagia, and postmenopausal bleeding. Transcatheter
      interventions include the following: (1) prophylactic selective catheterization
      of the internal iliac arteries, with either temporary balloon occlusion or
      embolotherapy; (2) selective embolization of collateral pelvic vessels in the
      setting of surgical ligation of the internal iliac arteries and/or delivery
      related injuries to the genital tract; (3) transarterial embolization for the
      management of abnormal placentation; and (4) massive bleeding secondary to
      uterine leiomyomas (fibroids) and/or arteriovenous malformations. Transcatheter
      embolization is a fast, safe, and effective minimally invasive alternative to
      hysterectomy, when medical treatment fails to control uterine bleeding. Moreover,
      it preserves the uterus with little or no significant impact on future
      pregnancies and fertility. This article reviews the transcatheter endovascular
      techniques that are used in a variety of clinical scenarios for the management of
      obstetrical and gynecologic emergencies.

PMID- 19853232
TI  - Acute deep vein thrombosis and thrombolysis.
AB  - Pulmonary embolism is a well-known and feared complication of deep venous
      thrombosis (DVT). Patients who present with acute DVT are treated with
      anticoagulation therapy whenever possible. Nonetheless, anticoagulation therapy
      does not actually treat DVT by dissolution of thrombus but instead prevents the
      propagation of the existing acute DVT. Unfortunately, a significant number of
      patients, particularly those with femoral or iliofemoral DVT, will develop the
      postthrombotic syndrome (PTS), despite receiving anticoagulation therapy. PTS is
      clinically manifested by leg pain, swelling, skin discoloration, and venous
      claudication; venous ulceration is the most severe form of PTS. The natural
      course of DVT is that of recanalization of the thrombosed segment, which may
      ultimately lead to venous insufficiency and/or reflux because of damage to the
      venous valves. Venous insufficiency, valvular incompetence, and reflux following
      DVT are known to play a major role in the development of PTS. Catheter-directed
      venous thrombolysis has been proposed as a means of reducing the risk of PTS, as
      this will actually dissolve the acute thrombus, restore venous patency, and, most
      importantly, restore venous valve function. This review examines the different
      techniques of thrombolysis and thrombectomy.

PMID- 19853233
TI  - Emergent nephrostomy tube placement for acute urinary obstruction.
AB  - Obstructive uropathy and urosepsis constitute a medical emergency and require
      emergent decompression of the urinary collecting system. Image-guided
      percutaneous nephrostomy tube placement using ultrasound and fluoroscopy allows
      for decompression of the obstructed renal collecting system with minimal
      complications.

PMID- 19853234
TI  - Biliary tract interventions.
AB  - Biliary tract interventions remain a tremendous technical challenge to the
      interventionalist and require appropriate clinical postprocedural management. The
      increased use of endoscopy for biliary tract evaluation and intervention has
      served to largely replace percutaneous techniques, resulting in a decreased
      number of patients requiring primary percutaneous transhepatic biliary
      interventions. However, those patients who do present for percutaneous biliary
      procedures often represent a more technically difficult subset. Thorough
      familiarity with normal and variant biliary tract anatomy, and experience with a
      variety of techniques, will allow for successful biliary tract interventions in
      complex situations. This article reviews the current role of percutaneous
      transhepatic interventions in the emergency evaluation and management of biliary
      tract disease.

PMID- 19853235
TI  - A distinct DNA-methylation boundary in the 5'- upstream sequence of the FMR1
      promoter binds nuclear proteins and is lost in fragile X syndrome.
AB  - We have discovered a distinct DNA-methylation boundary at a site between 650 and
      800 nucleotides upstream of the CGG repeat in the first exon of the human FMR1
      gene. This boundary, identified by bisulfite sequencing, is present in all human
      cell lines and cell types, irrespective of age, gender, and developmental stage.
      The same boundary is found also in different mouse tissues, although sequence
      homology between human and mouse in this region is only 46.7%. This boundary
      sequence, in both the unmethylated and the CpG-methylated modes, binds
      specifically to nuclear proteins from human cells. We interpret this boundary as
      carrying a specific chromatin structure that delineates a hypermethylated area in
      the genome from the unmethylated FMR1 promoter and protecting it from the
      spreading of DNA methylation. In individuals with the fragile X syndrome (FRAXA),
      the methylation boundary is lost; methylation has penetrated into the FMR1
      promoter and inactivated the FMR1 gene. In one FRAXA genome, the upstream
      terminus of the methylation boundary region exhibits decreased methylation as
      compared to that of healthy individuals. This finding suggests changes in
      nucleotide sequence and chromatin structure in the boundary region of this FRAXA
      individual. In the completely de novo methylated FMR1 promoter, there are
      isolated unmethylated CpG dinucleotides that are, however, not found when the
      FMR1 promoter and upstream sequences are methylated in vitro with the bacterial M
      SssI DNA methyltransferase. They may arise during de novo methylation only in DNA
      that is organized in chromatin and be due to the binding of specific proteins.

PMID- 19853236
TI  - Sequence variants in three loci influence monocyte counts and erythrocyte volume.
AB  - Blood cells participate in vital physiological processes, and their numbers are
      tightly regulated so that homeostasis is maintained. Disruption of key regulatory
      mechanisms underlies many blood-related Mendelian diseases but also contributes
      to more common disorders, including atherosclerosis. We searched for quantitative
      trait loci (QTL) for hematology traits through a whole-genome association study,
      because these could provide new insights into both hemopoeitic and disease
      mechanisms. We tested 1.8 million variants for association with 13 hematology
      traits measured in 6015 individuals from the Australian and Dutch populations.
      These traits included hemoglobin composition, platelet counts, and red blood cell
      and white blood cell indices. We identified three regions of strong association
      that, to our knowledge, have not been previously reported in the literature. The
      first was located in an intergenic region of chromosome 9q31 near LPAR1,
      explaining 1.5% of the variation in monocyte counts (best SNP rs7023923,
      p=8.9x10(-14)). The second locus was located on chromosome 6p21 and associated
      with mean cell erythrocyte volume (rs12661667, p=1.2x10(-9), 0.7% variance
      explained) in a region that spanned five genes, including CCND3, a member of the
      D-cyclin gene family that is involved in hematopoietic stem cell expansion. The
      third region was also associated with erythrocyte volume and was located in an
      intergenic region on chromosome 6q24 (rs592423, p=5.3x10(-9), 0.6% variance
      explained). All three loci replicated in an independent panel of 1543 individuals
      (p values=0.001, 9.9x10(-5), and 7x10(-5), respectively). The identification of
      these QTL provides new opportunities for furthering our understanding of the
      mechanisms regulating hemopoietic cell fate.

PMID- 19853238
TI  - Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause
      retinitis pigmentosa.
AB  - Bestrophin-1 is preferentially expressed at the basolateral membrane of the
      retinal pigmented epithelium (RPE) of the retina. Mutations in the BEST1 gene
      cause the retinal dystrophies vitelliform macular dystrophy, autosomal-dominant
      vitreochoroidopathy, and autosomal-recessive bestrophinopathy. Here, we describe
      four missense mutations in bestrophin-1, three that we believe are previously
      unreported, in patients diagnosed with autosomal-dominant and -recessive forms of
      retinitis pigmentosa (RP). The physiological function of bestrophin-1 remains
      poorly understood although its heterologous expression induces a Cl--specific
      current. We tested the effect of RP-causing variants on Cl- channel activity and
      cellular localization of bestrophin-1. Two (p.L140V and p.I205T) produced
      significantly decreased chloride-selective whole-cell currents in comparison to
      those of wild-type protein. In a model system of a polarized epithelium, two of
      three mutations (p.L140V and p.D228N) caused mislocalization of bestrophin-1 from
      the basolateral membrane to the cytoplasm. Mutations in bestrophin-1 are
      increasingly recognized as an important cause of inherited retinal dystrophy.

PMID- 19853237
TI  - Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation
      amelogenesis imperfecta.
AB  - Healthy dental enamel is the hardest and most highly mineralized human tissue.
      Though acellular, nonvital, and without capacity for turnover or repair, it can
      nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term
      for failure of normal enamel development, covering diverse clinical phenotypes
      that typically show Mendelian inheritance patterns. One subset, known as
      hypomaturation AI, is characterised by near-normal volumes of organic enamel
      matrix but with weak, creamy-brown opaque enamel that fails prematurely after
      tooth eruption. Mutations in genes critical to enamel matrix formation have been
      documented, but current understanding of other key events in enamel
      biomineralization is limited. We investigated autosomal-recessive hypomaturation
      AI in a consanguineous Pakistani family. A whole-genome SNP autozygosity screen
      identified a locus on chromosome 15q21.3. Sequencing candidate genes revealed a
      point mutation in the poorly characterized WDR72 gene. Screening of WDR72 in a
      panel of nine additional hypomaturation AI families revealed the same mutation in
      a second, apparently unrelated, Pakistani family and two further nonsense
      mutations in Omani families. Immunohistochemistry confirmed intracellular
      localization in maturation-stage ameloblasts. WDR72 function is unknown, but as a
      putative beta propeller is expected to be a scaffold for protein-protein
      interactions. The nearest homolog, WDR7, is involved in vesicle mobilization and
      Ca2+-dependent exocytosis at synapses. Vesicle trafficking is important in
      maturation-stage ameloblasts with respect to secretion into immature enamel and
      removal of cleaved enamel matrix proteins via endocytosis. This raises the
      intriguing possibility that WDR72 is critical to ameloblast vesicle turnover
      during enamel maturation.

PMID- 19853239
TI  - Identification of CANT1 mutations in Desbuquois dysplasia.
AB  - Desbuquois dysplasia is a severe condition characterized by short stature, joint
      laxity, scoliosis, and advanced carpal ossification with a delta phalanx.
      Studying nine Desbuquois families, we identified seven distinct mutations in the
      Calcium-Activated Nucleotidase 1 gene (CANT1), which encodes a soluble UDP
      preferring nucleotidase belonging to the apyrase family. Among the seven
      mutations, four were nonsense mutations (Del 5' UTR and exon 1, p.P245RfsX3,
      p.S303AfsX20, and p.W125X), and three were missense mutations (p.R300C, p.R300H,
      and p.P299L) responsible for the change of conserved amino acids located in the
      seventh nucleotidase conserved region (NRC). The arginine substitution at
      position 300 was identified in five out of nine families. The specific function
      of CANT1 is as yet unknown, but its substrates are involved in several major
      signaling functions, including Ca2+ release, through activation of pyrimidinergic
      signaling. Importantly, using RT-PCR analysis, we observed a specific expression
      in chondrocytes. We also found electron-dense material within distended rough
      endoplasmic reticulum in the fibroblasts of Desbuquois patients. Our findings
      demonstrate the specific involvement of a nucleotidase in the endochondral
      ossification process.

PMID- 19853240
TI  - Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme
      replacement therapy for Fabry disease.
AB  - A modified alpha-N-acetylgalactosaminidase (NAGA) with alpha-galactosidase A
      (GLA)-like substrate specificity was designed on the basis of structural studies
      and was produced in Chinese hamster ovary cells. The enzyme acquired the ability
      to catalyze the degradation of 4-methylumbelliferyl-alpha-D-galactopyranoside. It
      retained the original NAGA's stability in plasma and N-glycans containing many
      mannose 6-phosphate (M6P) residues, which are advantageous for uptake by cells
      via M6P receptors. There was no immunological cross-reactivity between the
      modified NAGA and GLA, and the modified NAGA did not react to serum from a
      patient with Fabry disease recurrently treated with a recombinant GLA. The enzyme
      cleaved globotriaosylceramide (Gb3) accumulated in cultured fibroblasts from a
      patient with Fabry disease. Furthermore, like recombinant GLA proteins presently
      used for enzyme replacement therapy (ERT) for Fabry disease, the enzyme
      intravenously injected into Fabry model mice prevented Gb3 storage in the liver,
      kidneys, and heart and improved the pathological changes in these organs. Because
      this modified NAGA is hardly expected to cause an allergic reaction in Fabry
      disease patients, it is highly promising as a new and safe enzyme for ERT for
      Fabry disease.

PMID- 19853241
TI  - The relationship between imputation error and statistical power in genetic
      association studies in diverse populations.
AB  - Genotype-imputation methods provide an essential technique for high-resolution
      genome-wide association (GWA) studies with millions of single-nucleotide
      polymorphisms. For optimal design and interpretation of imputation-based GWA
      studies, it is important to understand the connection between imputation error
      and power to detect associations at imputed markers. Here, using a 2x3 chi-square
      test, we describe a relationship between genotype-imputation error rates and the
      sample-size inflation required for achieving statistical power at an imputed
      marker equal to that obtained if genotypes at the marker were known with
      certainty. Surprisingly, typical imputation error rates (approximately 2%-6%)
      lead to a large increase in the required sample size (approximately 10%-60%), and
      in some African populations whose genotypes are particularly difficult to impute,
      the required sample-size increase is as high as approximately 30%-150%. In most
      populations, each 1% increase in imputation error leads to an increase of
      approximately 5%-13% in the sample size required for maintaining power. These
      results imply that in GWA sample-size calculations investigators will need to
      account for a potentially considerable loss of power from even low levels of
      imputation error and that development of additional genomic resources that
      decrease imputation error will translate into substantial reduction in the sample
      sizes needed for imputation-based detection of the variants that underlie complex
      human diseases.

PMID- 19853242
TI  - Effect of stimulus parameters and contraction level on inhibitory responses in
      human jaw-closing muscles: Implications for contingent stimulation.
AB  - OBJECTIVE: Examine the effect of stimulus duration, intensity and level of muscle
      contraction on the inhibitory responses evoked by electrical stimuli in human jaw
      closing muscles applied to the right mental nerve. DESIGN: The inhibitory jaw
      reflexes, short-latency (ES1) and long-latency (ES2), were recorded in the
      surface electromyogram (EMG) of masseter and temporalis muscles in 16 healthy
      subjects. Three stimulus durations (1ms single square-wave pulse, 10 and 450ms
      square-wave pulse train), two stimulus intensities adjusted to perceived
      intensity of 3 (non-painful) and 7 (distinct painful) on a 0-10 verbal rating
      scale were applied to the right mental nerve while the subject was biting at 25%
      and 50% of the maximal voluntary contraction (MVC). RESULTS: The magnitude of
      suppression in the ES2 evoked by 1 and 10ms stimuli was dependent on stimulus
      intensity (P<0.002 and P<0.001, respectively) but not contraction level. However,
      ES1 could not be observed in most of the recordings. There were significant
      decreases evoked by the 450ms stimuli in RMS-EMG values in the 400-500ms compared
      with the pre-stimulus interval (P<0.001) which was dependent on contraction level
      (P<0.01) but not on stimulus intensity (P=0.486). CONCLUSIONS: The present
      results suggest that the ES2 reflex response is associated with the duration of
      the electrical stimuli, the intensity level but not the contraction level. In
      contrast, the inhibitory effects of ultra-long stimuli (450ms) are not
      specifically related to the intensity level suggesting that this is a non
      nociceptive response.

PMID- 19853243
TI  - Comparing the role of psychological flexibility and traditional pain management
      coping strategies in chronic pain treatment outcomes.
AB  - Psychologically-based interventions for chronic pain traditionally include a mix
      of methods, including physical conditioning, training in relaxation or attention
      control, strategies to decrease irrational or dysfunctional thinking patterns,
      and activity management training. Recent developments suggest additional methods
      to promote acceptance, mindfulness, values-based action, and cognitive defusion
      (a cognitive process entailing change in the influences exerted by thoughts
      without necessarily changing their form or frequency). Collectively, these
      processes entail what is referred to as psychological flexibility. This study
      examined how changes in traditionally conceived methods of coping compare to
      changes in psychological flexibility in relation to improvements in functioning
      over the course of an interdisciplinary treatment program. Participants were 114
      chronic pain sufferers. Results indicated that changes in the traditionally
      conceived methods were essentially unrelated to treatment improvements, while
      changes in psychological flexibility were consistently and significantly related
      to these improvements. We suggest that psychological flexibility appears highly
      relevant to the study of chronic pain and to future treatment developments. The
      utility of more traditionally conceived pain management strategies, on the other
      hand, may require a reappraisal.

PMID- 19853244
TI  - Reactions of phenyl and ethyl 2-O-sulfonyl-1-thio-alpha-D-manno- and beta-D
      glucopyranosides with thionucleophiles.
AB  - Persubstituted derivatives of phenyl and ethyl 2-O-sulfonyl-1-thio-alpha-D-manno-
      and beta-D-glucopyranosides were synthesized and reacted either with PhSNa or
      with MeSNa. The phenyl-1-thio compounds afforded the dithio-1,2-cis
      axial/equatorial-alpha-D-glucopyranosides or dithio-1,2-cis-equatorial/axial-beta
      D-mannopyranosides by means of S(N)2 type of reactions. Starting from the ethyl-1
      thio derivatives intramolecular 1,2-thio-migration took place predominantly. In
      the case of mannosides both nucleophilic reagents facilitate the formation of 1
      SPh- or 1-SEt glycals by elimination. The formation of unsubstituted glycal could
      also be observed from the ethyl-1-thio derivatives, especially by using PhSNa as
      a nucleophile. The 1,2-dithio-glycosides are glycosyl donors affording 1,2-trans
      2-thio-glycosides.

PMID- 19853246
TI  - A motion aftereffect from visual imagery of motion.
AB  - Mental imagery is thought to share properties with perception. To what extent
      does the process of imagining a scene share neural circuits and computational
      mechanisms with actually perceiving the same scene? Here, we investigated whether
      mental imagery of motion in a particular direction recruits neural circuits tuned
      to the same direction of perceptual motion. To address this question we made use
      of a visual illusion, the motion aftereffect. We found that following prolonged
      imagery of motion in one direction, people are more likely to perceive real
      motion test probes as moving in the direction opposite to the direction of motion
      imagery. The transfer of adaptation from imagined to perceived motion provides
      evidence that motion imagery and motion perception recruit shared direction
      selective neural circuitry. Even in the absence of any visual stimuli, people can
      selectively recruit specific low-level sensory neurons through mental imagery.

PMID- 19853245
TI  - Identification of (1-->6)-beta-D-glucan as the major carbohydrate component of
      the Malassezia sympodialis cell wall.
AB  - Members of the genus Malassezia are commensal fungi found on the skin of both
      human and domestic animals and are associated with skin diseases including
      dandruff/seborrheic dermatitis, pityriasis versicolor, and atopic eczema (AE) in
      humans. In this study we have characterized the cell-wall carbohydrates of
      Malassezia sympodialis, one of the species most frequently isolated from both AE
      patients and healthy individuals. Cells were grown in liquid Dixon media at 32
      degrees C, harvested, and processed using a standard Fehling's precipitation
      methodology for the isolation of mannan and a standard base/acid extraction for
      (1-->3)-beta-D-glucans. Using these classic extraction methods we were unable to
      isolate precipitable mannan or insoluble (1-->3)-beta-D-glucan. However,
      acidification and addition of methanol to the remaining Fehling's-treated sample
      resulted in a very clean precipitate. This material was characterized by GPC
      MALLS, 1D and 2D NMR, and GC-MS for monomer-type and linkage-type composition. We
      determined that trace amounts of both mannan and branched (1-->3, 1-->6)-beta-D
      glucan were present in the recovered precipitate, but not linear (1-->3)-beta-D
      glucan. Surprisingly, NMR analysis indicated that (1-->6)-beta-D-glucan was the
      major carbohydrate component isolated from M. sympodialis cell wall. GC-MS
      linkage analysis confirmed the (1-->6)-beta-D-glucan structure. Based on these
      studies we have determined that the M. sympodialis cell wall contains (1-->6)
      beta-D-glucan as the major carbohydrate component along with trace amounts of
      mannan and (1-->3, 1-->6)-beta-d-glucan. In addition, these data indicate that
      modification of the classic mannan isolation methodology may be useful in the
      simultaneous isolation of both mannan and (1-->6)-beta-D-glucan from other fungi.

PMID- 19853247
TI  - Functional activation in the cerebellum during working memory and simple speech
      tasks.
AB  - Verbal working memory is the ability to temporarily store and manipulate verbal
      information. This study tested the predictions of a neuroanatomical model of how
      the cerebellum contributes to verbal working memory (Desmond et al., 1997). In
      this model, a large bilateral region in the superior cerebellum is associated
      with articulatory rehearsal and a right-lateralized region in the inferior
      cerebellum is associated with the correction of errors within the working memory
      system. The Desmond et al. (1997) model was based on neuroimaging findings using
      item recognition tasks and comparisons between working memory and covert
      rehearsal tasks, whereas in this functional magnetic resonance imaging (fMRI)
      study we used a delayed serial recall (DSR) task because it relies more heavily
      on articulatory rehearsal, and our comparison tasks included both overt and
      covert speech tasks. Our results provide some support for the Desmond et al.
      (1997) model. In particular, we found multiple activation foci within the
      superior and inferior sectors of the cerebellum and evidence that these regions
      show different patterns of activation across working memory and speech tasks.
      However, the specific patterns of activation were not fully consistent with those
      reported by Desmond et al. (1997). Namely, our results indicate that activation
      in the superior sector should be functionally subdivided into a medial focus
      involved in speech processing and a lateral focus more specific to verbal working
      memory; the results also indicate that activation in the inferior sector is not
      uniquely right lateralized. These complex findings speak to the need for future
      studies to consider the speech-motor aspects of tasks, to investigate the
      functional significance of adjacent peaks of activation within large regions of
      cerebellar activation, and to use analysis procedures that support regional
      distinctions through direct statistical tests. Such studies would help to refine
      our understanding of how the cerebellum contributes to speech and verbal working
      memory.

PMID- 19853248
TI  - Covert processing of facial expressions by people with Williams syndrome.
AB  - Although individuals with Williams Syndrome (WS) are empathic and sociable and
      perform relatively well on face recognition tasks, they perform poorly on tasks
      of facial expression recognition. The current study sought to investigate this
      seeming inconsistency. Participants were tested on a Garner-type matching
      paradigm in which identities and expressions were manipulated simultaneously as
      the relevant or irrelevant dimensions. Performance of people with WS on the
      expression-matching task was poor and relied primarily on facilitation afforded
      by congruent identities. Performance on the identity matching task came close to
      the level of performance of matched controls and was significantly facilitated by
      congruent expressions. We discuss potential accounts for the discrepant
      processing of expressions in the task-relevant (overt) and task-irrelevant
      (covert) conditions, expanding on the inherently semantic-conceptual nature of
      overt expression matching and its dependence on general cognitive level.

PMID- 19853249
TI  - Height of skull base as an indicator of living conditions in historical native
      populations from Europe, Australia and Africa.
AB  - Flattening and lowering of the skull base in response to improper bone growth is
      called platybasis, and is considered a sensitive and reliable indicator of
      adverse living conditions such as malnutrition and disease during the prenatal
      period and early childhood. The degree of platybasis was assessed in three series
      of skulls representing geographically distinct historical native populations from
      Europe, Australia and Africa. Platybasis was determined by measuring the height
      of the base of the skull. The degree of platybasis varied among the populations
      examined, and was the lowest in the Australian group, and the highest in the
      African group. This may be due to either variability of living conditions or
      genetic factors, which have an influence on robusticity and cranial architecture.
      There were also differences among the groups in terms of the other skull
      measurements and indices examined. The height of the base of the skull was
      generally greater in males than in females, which indicates sexual dimorphism or
      fact that females had worse living conditions. Correlation coefficients between
      the height of the base of the skull and other measurements including skull length
      and skull width were also calculated indicating significant relationships. The
      differences between the height of the base of the skull and height/length index
      and height/width index, were statistically significant.

PMID- 19853250
TI  - Sexual dimorphism in southeast Asian crania: a geometric morphometric approach.
AB  - Despite a number of studies stating that sexual dimorphism is population
      specific, sexual differences in Southeast Asian populations have received little
      attention. Previous studies in this region have focused on samples from Thailand
      or East Asian populations from China and Japan, examining sexual dimorphism
      predominantly of the postcranial bones, teeth and mandible with comparatively few
      cranial studies. These earlier studies have used traditional methods to
      metrically assess differences between the sexes. The aim of this study is to use
      geometric morphometric methods for the first time to quantify sexual dimorphism
      of Southeast Asian crania and extend knowledge of cranial sexual dimorphism
      beyond China, Japan and Thailand. A total of 35 unilateral and midline landmark
      coordinates were collected from 144 mainland and island Southeast Asian crania
      (89 male, 55 female). Using the shape analysis software Morphologika, principal
      components analysis and thin plate splines allowed for the statistical and visual
      exploration of shape differences. Differences included relative facial breadth,
      particularly across the zygomatic and postorbital regions and cranial vault
      breadth. Significant size dimorphism was also apparent. Overall expected
      accuracies were highest in the discriminant analysis using both shape and
      centroid size (86.8%).

PMID- 19853251
TI  - A systematic review of the costs and benefits of helicopter emergency medical
      services.
AB  - INTRODUCTION: Helicopter emergency medical services (HEMS) are popular in first
      world health systems despite inconsistent evidence in the scientific literature
      to support their use. The aim of the current study was to perform a systematic
      review of economic evaluations of HEMS, in order to determine the economic cost
      of HEMS and the associated patient-centered benefits. METHOD: A systematic review
      was performed of studies that provided a cost estimate of HEMS. The inclusion
      criteria consisted of English language articles that estimated both the costs and
      outcomes of a HEMS and fulfilled pre-specified criteria in relation to a cost
      analysis, cost-minimisation, cost-effectiveness or cost-benefit evaluation.
      Identified studies were synthesised according to the patient diagnosis (trauma,
      non-trauma or non-specific) and the type of HEMS transport under review (primary
      scene retrieval or secondary inter-facility transport). All costs were converted
      to US dollars and indexed for inflation. RESULTS: Fifteen studies met the
      inclusion criteria. Among all studies the annual cost of HEMS ranged from
      $115,777 to $5,571,578. Five studies showed HEMS to be a more expensive transport
      alternative without an associated benefit while eight studies provided cost
      effectiveness ratios of $3292 and $2227 per life year saved for trauma, $3258 per
      life saved and $7138 and $12,022 per quality adjusted life year for non-trauma
      and $30,365 and $91,478 per beneficial mission for non-specific patient
      populations. One study also evaluated the cost of HEMS to societal benefit,
      producing a ratio of 1:6. INTERPRETATION: The cost and effectiveness of HEMS
      varied considerably between studies. Despite generally being more expensive than
      ground transport, a number of studies found HEMS to be cost-effective. However,
      given the variation in the intervention design, context and study methods between
      studies it was not possible to assess the cost-effectiveness of HEMS in general.
      Given the variation inherent in the health systems in which HEMS operate,
      synthesis and extrapolation of study findings across differing health
      environments is difficult. To address economic and clinical evidence in relation
      to HEMS, future research that is tailored to account for local system factors is
      required.

PMID- 19853252
TI  - [Laparoscopic hysterectomy in 10 steps].

PMID- 19853253
TI  - Beyond the antioxidant properties: pomegranate juice polyphenols increase
      hepatocyte paraoxonase 1 secretion.

PMID- 19853254
TI  - Use of non-porous pillar array columns for the separation of Pseudomonas
      pyoverdine siderophores as an example of a real-world biological sample.
AB  - We report on the first separation of a complex biomixture in pressure-driven mode
      using perfectly ordered pillar array columns. The separations were conducted in
      the reversed-phase mode using a highly aqueous mobile phase, while the outer
      surface of the non-porous pillars was chemically functionalized with a
      hydrophobic C8-layer. The samples originated from two different bacterial strains
      (Pseudomonas aeruginosa PAO1 and Pseudomonas sp. W15Feb38) of fluorescent
      pseudomonads. These produce fluorescent yellow-green pyoverdines that serve as
      siderophores to shuttle iron inside the cell. The pyoverdines of both strains
      were prepared from the supernatant through a crude solid phase extraction without
      any further purification step. In case of the PAO1 mixture, a separation of 15
      components within a column length of 2.5 cm could be observed through the
      transparent cover glass of the chip. For the W15Feb38 mixture, a separation of
      eight components could be observed within the same distance. These fast
      chromatographic separations were compared with those obtained via iso
      electrofocusing (IEF), which is the traditionally employed fingerprinting method
      to characterize pseudomonad strains based on their pyoverdine profiles
      (siderotyping). With this technique, and despite the injection of a 10,000 times
      larger sample mass, only nine bands were maximally observed for the PAO1 mixture,
      whereas maximally six bands were observed in case of the W15Feb38 mixture. The
      chromatographic pillar array method, yielding a separation in less than 1 min,
      was also significantly faster than the IEF method, which typically needs 1.5h.
      The present system can therefore be considered as a potential alternative
      fingerprinting tool for the fast identification of different strains of
      fluorescent pseudomonads, including as diagnostic tool for typing strains of the
      important opportunistic pathogen P. aeruginosa.

PMID- 19853255
TI  - Preparation of a mixed stir bar for sorptive extraction based on monolithic
      material for the extraction of quinolones from wastewater.
AB  - In this study, a novel mixed mode monolithic material was prepared and acted as
      the SBSE coating. The monolithic material was prepared by in situ
      copolymerization of methacrylic acid-3-sulfopropyl ester potassium salt (MASE)
      and divinylbenzene (DB) in the presence of a porogen solvent containing
      cyclohexanol, 1-dodecanol, and water with azobisisobutyronitrile as initiator.
      The influences of the contents of the porogen solvent and monomer in the
      polymerization mixture on the extraction performance were investigated
      thoroughly. Several characteristic techniques, such as elemental analysis,
      scanning electron microscopy and infrared spectroscopy were used to characterize
      the monolithic material. To achieve optimum extraction performance for
      quinolones, several parameters, including pH value, desorption solvent, ionic
      strength in sample matrix, extraction and desorption time were investigated. The
      results show that under the optimized experimental conditions, the method has
      good sensitivity, linearity, simplicity and low cost. The extraction performance
      of present method to the target compounds was compared with commercial SBSE which
      using polydimethylsiloxane as coating and other SBSEs which based on monolithic
      materials. The comparative results indicate that present SBSE can extract the
      analytes more effectively than other SBSEs because both ion-exchange and
      hydrophobic interactions contribute to the extraction of quinolones.

PMID- 19853256
TI  - Identification of sildenafil, tadalafil and vardenafil by gas chromatography-mass
      spectrometry on short capillary column.
AB  - Sildenafil and its analogues (tadalafil and vardenafil) are phosphodiesterase
      type 5 inhibitors used in the treatment of male erectile dysfunction. Some
      dietary supplements, herbal preparations and food products which claim to enhance
      male sexual function have been found to be adulterated with these drugs. In this
      study, a gas chromatograph-mass spectrometer (GC-MS) assay was developed for
      identification of the drugs. In addition to good and short chromatographic
      separation that can be achieved within 6 min by using a short 10 m capillary
      column, no prior sample clean-up before GC-MS analysis was required, thus making
      this assay a cost saving and rapid method. Furthermore, the assay is specific as
      the identification of sildenafil, tadalafil and vardenafil were done by detection
      of molecular ions; m/z 474, 389 and 488, [corrected] respectively, and several
      other characteristic ions resulted from the mass fragmentation of individual
      molecules. Using our currently developed assay, sildenafil and its analogues were
      successfully identified in food and herbal matrices.

PMID- 19853257
TI  - Comparison of the adsorption mechanisms of pyridine in hydrophilic interaction
      chromatography and in reversed-phase aqueous liquid chromatography.
AB  - The adsorption isotherms of pyridine were measured by frontal analysis (FA) on a
      column packed with shell particles of neat porous silica (Halo), using water
      acetonitrile mixtures as the mobile phase at 295K. The isotherm data were
      measured for pyridine concentrations covering a dynamic range of four millions.
      The degree of heterogeneity of the surface was characterized by the adsorption
      energy distribution (AED) function calculated from the raw adsorption data, using
      the expectation-maximization (EM) procedure. The results showed that two
      different retention mechanisms dominate in Per aqueous liquid chromatography
      (PALC) at low acetonitrile concentrations and in hydrophilic interaction
      chromatography (HILIC) at high acetonitrile concentrations. In the PALC mode, the
      adsorption mechanism of pyridine on the silica surface is controlled by
      hydrophobic interactions that take place on very few and ultra-active adsorption
      sites, which might be pores on the irregular and rugose surface of the porous
      silica particles. The surface is seriously heterogeneous, with up to five
      distinct adsorption sites and five different energy peaks on the AED of the
      packing material. In contrast, in the HILIC mode, the adsorption behavior is
      quasi-homogeneous and pyridine retention is governed by its adsorption onto free
      silanol groups. For intermediate mobile phase compositions, the siloxane and the
      silanol groups are both significantly saturated with acetonitrile and water,
      respectively, causing a minimum of the retention factor of pyridine on the Halo
      column.

PMID- 19853258
TI  - On the effect of a non-ionic surfactant on the surface of sucrose crystals and on
      the crystal growth process by inverse gas chromatography.
AB  - The effect of Hodag CB6, a widely used non-ionic surfactant in sugar
      crystallization process, on the surface properties of sucrose was studied in
      detail by inverse gas chromatography (IGC) experiments. IGC experiments were
      performed with pure sucrose crystals, surfactant coated sucrose crystals, and
      crystals grown in the presence of surfactant at 313.05 and 323.05 K. The
      surfactant promotes the specific interactions with the polar probes. The sorption
      of basic, acidic and amphoteric probes onto pure and surfactant coated sucrose
      was found to be endothermic and in the case of neutral probes was found to be
      exothermic. The surfactant increases both the acidity and basicity of the sucrose
      surface with the latter effect being significant. The role of interfacial tension
      on the growth kinetics of sucrose crystals was studied using IGC for different
      surfactant concentrations. IGC results with the surfactant coated sucrose were
      used to interpret the thermodynamic effect of surfactants during the crystal
      growth process. The dispersive component of the surface energy, gamma(s)(D), of
      surfactant coated sucrose crystals was found to be lower than that of pure
      sucrose crystals and was found to be in the range of 33.49-35.27 mJ/m(2).

PMID- 19853259
TI  - Encapsulation of polyaniline in 3-D interconnected mesopores of silica KIT-6.
AB  - Composite material PANI/KIT-6, with polyaniline (PANI) chains encapsulated in the
      3-D interconnected pore channels of mesoporous silica, KIT-6, has been
      synthesized via a gas-phase method. The composite formation and the presence of
      PANI inside the pore channels of KIT-6 were evidenced by Fourier transform
      infrared spectroscopy (FTIR), scanning electron microscopy (SEM), small-angle X
      ray scatter (SAXS), transmission electron microscopy (TEM), and N(2) adsorption
      desorption isotherms. The PANI/KIT-6 composite showed good electrical
      conductivity (2.4x10(-3) S/cm) due to the formation of 3-D networks of PANI
      inside the 3-D interconnected channels of KIT-6. The resistance of PANI/KIT-6
      composite at different relative humidities (RH) was investigated. An essentially
      linear relationship between the relative resistance of the composite and the
      relative humidity of the environment was found from 11.3% to 97.3% RH.

PMID- 19853260
TI  - In vitro activation of human peripheral blood mononuclear cells induced by human
      biologic meshes.
AB  - BACKGROUND: Inflammation and wound healing play critical roles in the integration
      of biologic meshes (BMs) at sites of hernia repair. Monocytes/macrophages (M/MQs)
      are key cells involved in mesh integration. Interleukin-1beta (IL-1beta) is one
      of the major M/MQ-derived cytokines, and its expression is a reflection of the
      degree of M/MQ activation. We hypothesized that BMs induce M/MQ activation in
      vitro and that IL-1beta expression by M/MQ varies among various BMs. MATERIALS
      AND METHODS: Acellular human dermis-derived BM samples (AlloDerm, AlloMax,
      FlexHD) were placed in 48-well plates and cultured with peripheral blood
      mononuclear cells (PBMCs) from three healthy human subjects for 7 d. The
      resulting supernatants were assayed for IL-1beta levels by enzyme-linked
      immunosorbent assay (ELISA), and the BMs were evaluated histologically. RESULTS:
      IL-1beta expression varied among donors as well as the BMs [AlloDerm (2.11
      38.25pg/10(6) PBMCs); AlloMax (13.12-715.40pg/10(6) PBMCs); and FlexHD (116.69
      665.40pg/10(6) PBMCs)]. Analysis of this data indicated that AlloMax and FlexHD
      induced significantly more M/MQ activation compared with AlloDerm (P<0.05).
      Histologic evaluation of the BMs indicated adherence of M/MQs on BM surface,
      however no degradation was detected. CONCLUSION: For the first time, we have
      demonstrated that M/MQs are activated to varying levels by human BMs in vitro.
      These differences may be related to BM processing technologies and/or the
      biologic variation between donors. Our results raise the possibility that these
      differences in M/MQ activation could result in varying intensity of inflammation
      and wound healing that control the integration of BMs at sites of hernia repair.

PMID- 19853261
TI  - Combined treatment with cisplatin and sirolimus to enhance cell death in human
      mesothelioma.
AB  - OBJECTIVE: Although platinum-based chemotherapy is widely used in malignant
      pleural mesothelioma, its modest therapeutic effect warrants identification of
      enhancing agents. As with many cancers, the phosphatidylinositol 3-kinase/Akt
      pathway is often activated in malignant pleural mesothelioma and has been
      implicated in the tumor's aggressiveness. Sirolimus is a well-established
      inhibitor of the mammalian target of rapamycin. We sought to determine whether
      combination treatment with sirolimus and cisplatin would enhance cell death in
      malignant pleural mesothelioma. METHODS: Human malignant pleural mesothelioma
      cell lines were incubated with sirolimus or cisplatin alone or in combination and
      assayed for cell viability. To characterize phosphorylation status after
      treatment, Akt and downstream proteins of mammalian target of rapamycin pathway,
      p70 S6 kinase and 4E-BP1, were analyzed by Western blot. Effect of combination
      treatment was also analyzed with extreme drug resistance assay in 12 human
      malignant pleural mesothelioma tumors with varying resistance to cisplatin.
      RESULTS: Individual malignant pleural mesothelioma cell lines exhibited a range
      of sensitivities to each drug without correlation with subtype. Sirolimus and
      cisplatin significantly (P = .029) increased cell death versus either drug alone
      in 4 cell lines. Combined treatment caused dephosphorylation of Akt, 4E-BP1, and
      p70 S6 kinase. Cell proliferation was significantly decreased in tumors subjected
      to sirolimus and cisplatin versus cisplatin or sirolimus alone. CONCLUSIONS:
      Sirolimus appears to enhance the cytotoxicity of cisplatin in malignant pleural
      mesothelioma cell lines through the mammalian target of rapamycin pathway. These
      results provide a basis for the clinical evaluation of combined sirolimus and
      cisplatin chemotherapy in malignant pleural mesothelioma.

PMID- 19853262
TI  - Benthic foraminifera response and geochemical characterization of the coastal
      environment surrounding the polluted industrial area of Portovesme (South-Western
      Sardinia, Italy).
AB  - To study the benthic foraminifers' response to heavy metal pollution and analyse
      the geochemical parameters, samples of surface sediments were collected in 2005
      and 2006 from a polluted coastal zone shorefront to the industrial complex of
      Portoscuso-Portovesme (Sulcis, South-Western Sardinia). The samples came from the
      upper 1-2 cm of the undisturbed sediments in water less than 2m deep, along
      coastline (about 8.5 km in length) proximal to emerged alluvial plain. The entire
      examined marine area represents a shallow inner shelf, which is physiographically
      fairly protected and characterized by low turbulence, but subjected to southwards
      littoral drift. Geochemical analyses of seawater, sediments and foraminiferal
      tests correlated to biotic indexes (Dominance, Shannon-Weaver, Simpson, Eveness,
      Menhinick, Margalef, Equitability, Fisher-alpha, Berger-Parker and Q-mode Cluster
      Analyses--Ward Method) and provide data on environmental stress. A total of 38
      benthic foraminiferal species were identified. Increasing pollution results in
      low species diversity, low population density and more frequent abnormal
      specimens. Results from ESEM images allow recognition of a strong infestation on
      the calcareous foraminiferal tests by microbial communities developed in the
      polluted environment.

PMID- 19853263
TI  - [Molecular genetic reports in clinical practice: content and nomenclature of
      mutations].

PMID- 19853264
TI  - [Transient osteoporosis of the hip and pregnancy].

PMID- 19853265
TI  - Metabolic profiles of sunflower genotypes with contrasting response to
      Sclerotinia sclerotiorum infection.
AB  - We report a comprehensive primary metabolite profiling of sunflower (Helianthus
      annuus) genotypes displaying contrasting behavior to Sclerotinia sclerotiorum
      infection. Applying a GC-MS-based metabolite profiling approach, we were able to
      identify differential patterns involving a total of 63 metabolites including
      major and minor sugars and sugar alcohols, organic acids, amino acids, fatty
      acids and few soluble secondary metabolites in the sunflower capitulum, the main
      target organ of pathogen attack. Metabolic changes and disease incidence of the
      two contrasting genotypes were determined throughout the main infection period
      (R5.2-R6). Both point-by-point and non-parametric statistical analyses showed
      metabolic differences between genotypes as well as interaction effects between
      genotype and time after inoculation. Network correlation analyses suggested that
      these metabolic changes were synchronized in a time-dependent manner in response
      to the pathogen. Concerted differential metabolic changes were detected to a
      higher extent in the susceptible, rather than the resistant genotype, thereby
      allowing differentiation of modules composed by intermediates of the same pathway
      which are highly interconnected in the susceptible line but not in the resistant
      one. Evaluation of these data also demonstrated a genotype specific regulation of
      distinct metabolic pathways, suggesting the importance of detection of metabolic
      patterns rather than specific metabolite changes when looking for metabolic
      markers differentially responding to pathogen infection. In summary, the GC-MS
      strategy developed in this study was suitable for detection of differences in
      carbon primary metabolism in sunflower capitulum, a tissue which is the main
      entry point for this and other pathogens which cause great detrimental impact on
      crop yield.

PMID- 19853266
TI  - [A case of temporary nonthrombotic hemiplegia and aphasia due to neurotoxicity
      from angiographic contrast material?].
AB  - We present the case of a 75-year-old woman who suddenly developed hemiplegia,
      aphasia, and reduced consciousness three hours after embolization of a cerebral
      aneurysm. No complications occurred during embolization and the findings at end
      procedure angiography were normal. Cranial computed tomography (CT) after
      embolization showed hyperdensity of the cortex and sulci of the convexity;
      another CT examination performed four hours later showed these findings had
      disappeared. Cerebral arteriography 24h after embolization showed delayed blood
      flow to the parenchyma of the left hemisphere compared to the right but no
      vascular occlusion. The neurological deficit lasted 72 h and resolved
      spontaneously and completely as suddenly as it developed. This is one of the few
      cases of temporary neurological deficit related to iodinated contrast
      administration to be reported outside the posterior circulation (cortical
      blindness). When neurological symptoms occur after endovascular procedures in the
      brain, it is fundamental to distinguish this rare clinical syndrome of probable
      toxic origin from possible ischemic complications of the procedure.

PMID- 19853267
TI  - Distribution and morphology of argyrophilic cells in the digestive tract of the
      African ostrich.
AB  - We used light microscopy to elucidate the morphological features of argyrophilic
      cells in the digestive tract of the African ostrich (Struthio camelus). The
      results indicated that argyrophilic cells were found to be distributed among the
      epithelial cells of the mucosa or glands throughout the digestive tract, except
      for the esophagus; two types of argyrophilic cells were found; i.e., closed-type
      cells and cells with triangular or elongated shapes and with their apical
      cytoplasmic process in contact with the lumen (open-type cells); the greatest
      number of argyrophilic cells was found in the proventriculus, and the
      argyrophilic cell density gradually decreased from the proventriculus to the
      rectum; Furthermore, the number of argyrophilic cells in the duodenum and ileum
      was higher than that in the jejunum. This text still combined the characteristics
      that the argyrophilic cells in digestive tract of ostrich maybe related to
      different digestive function of different region and the basis of their
      morphology to carry on a discussion. It was speculated that argyrophilic cells in
      the digestive tract may have both endocrine and exocrine functions.

PMID- 19853268
TI  - Hydrodynamic sono-voltammetry of ferrocene in [Tf2N]- based ionic liquid media.
AB  - The present work deals with the hydrodynamic behavior of several room-temperature
      ionic liquids presenting the same bis(trifluoromethanesulfonyles)imide anion,
      associated with four different cations: 1-butyl-3-methylimidazolium, 1-octyl-3
      methylimidazolium, N-trimethyl-N-propylammonium and 1-butyl-1-methylpyrrolidinium
      cations. Steady state voltammetry was used as an electrochemical technique to
      characterize mass transfer in both silent and sonicated conditions, using a
      rotating disk electrode. Results obtained in RTILs media are compared to those
      acquired in synthetic solutions of controlled viscosity, in order to develop a
      better understanding of the phenomena involved in such media.

PMID- 19853269
TI  - Ultrasonic material characterization using large-aperture PVDF receivers.
AB  - This work describes the use of a large-aperture PVDF receiver in the measurement
      of liquid density and composite material elastic constants. The density
      measurement of several liquids is obtained with accuracy of 0.2% using a
      conventional NDE emitter transducer and a 70-mm-diameter, 52-microm P(VDF-TrFE)
      membrane with gold electrodes. The determination of the elastic constants is
      based on the phase velocity measurement. Diffraction can lead to errors around 1%
      in velocity measurement when using alternatively the conventional pair of
      ultrasonic transducers (1-MHz frequency and 19-mm-diameter) operating in through
      transmission mode, separated by a distance of 100 mm. This effect is negligible
      when using a pair of 10-MHz, 19-mm-diameter transducers. Nevertheless, the
      dispersion at 10 MHz can result in errors of about 0.5%, when measuring the
      velocity in composite materials. The use of an 80-mm diameter, 52-microm-thick
      PVDF membrane receiver practically eliminates the diffraction effects in phase
      velocity measurement. The elastic constants of a carbon fiber reinforced polymer
      were determined and compared with the values obtained by a tensile test.

PMID- 19853270
TI  - Current topics on sonoelectrochemistry.
AB  - Sonoelectrochemistry is undergoing a reemerging activity in the last years with
      an increasing number of papers appearing in a wide range of peer review journals.
      Applied studies which cover environmental treatments, synthesis or
      characterization of nanostructures, polymeric materials synthesis, analytical
      procedures, films preparations, membrane preparations among other interesting
      applications have been reviewed. The revised fundamental analyses trying to
      elucidate the mechanism of the interactions between the ultrasound and electrical
      fields, are focused on test electrochemical processes, on the use of
      unconventional solvents and combination with other techniques. After the review
      of the achievements and faults of sonoelectrochemistry, future research lines are
      suggested.

PMID- 19853272
TI  - Degradation of fifteen emerging contaminants at microg L(-1) initial
      concentrations by mild solar photo-Fenton in MWTP effluents.
AB  - The degradation of 15 emerging contaminants (ECs) at low concentrations in
      simulated and real effluent of municipal wastewater treatment plant with photo
      Fenton at unchanged pH and Fe=5 mg L(-1) in a pilot-scale solar CPC reactor was
      studied. The degradation of those 15 compounds (Acetaminophen, Antipyrine,
      Atrazine, Caffeine, Carbamazepine, Diclofenac, Flumequine, Hydroxybiphenyl,
      Ibuprofen, Isoproturon, Ketorolac, Ofloxacin, Progesterone, Sulfamethoxazole and
      Triclosan), each with an initial concentration of 100 microg L(-1), was found to
      depend on the presence of CO(3)(2-) and HCO(3)(-) (hydroxyl radicals scavengers)
      and on the type of water (simulated water, simulated effluent wastewater and real
      effluent wastewater), but is relatively independent of pH, the type of acid used
      for release of hydroxyl radicals scavengers and the initial H(2)O(2)
      concentration used. Toxicity tests with Vibrio fisheri showed that degradation of
      the compounds in real effluent wastewater led to toxicity increase.

PMID- 19853273
TI  - In ovo nanoinjection of nonylphenol affects embryonic development of a transgenic
      see-through medaka (Oryzias latipes), olvas-GFP/STII-YI strain.
AB  - We performed in ovo nanoinjection of 4-nonylphenol (NP) into embryos of a
      transgenic see-through medaka (Oryzias latipes), olvas-GFP/STII-YI strain, which
      has two genotypic sex markers, and examined the effects on development and sexual
      differentiation. The transgene consisted of a green fluorescent protein (GFP)
      gene fused to the regulatory region of the medaka vasa gene. Germ cell-specific
      GFP expression was visualized in the gonad through the transparent body wall of
      the living fish. The development of each embryo was observed after nanoinjection
      of 2.0, 10, 50, 125, or 250 ng of NP. NP administration caused significant higher
      mortality at > or = 50 ng egg(-1) and inhibited embryonic development, including
      abnormal hatch and swim-up failure in all treatment groups except 10 ng egg(-1)
      group. However, it did not cause adverse effects on germ cell proliferation by
      10d posthatch (dph) or sex differentiation of survivors by 100 dph. We concluded
      that single-dose in ovo exposure to nonylphenol affected embryonic development in
      the medaka but not gonadal development by 10 dph or sexual differentiation in
      adult fish by 100 dph. Although further investigations might be needed to
      elucidate the usefulness of nanoinjection of embryos of this strain, present
      study indicated that the nanoinjection model using olvas-GFP/STII-YI strain
      medaka has potential for use in evaluating the effects of chemicals on early
      development and sexual differentiation.

PMID- 19853271
TI  - A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral
      agents in vitro and in vivo.
AB  - Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease
      caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to
      facilitate antiviral research. We adapted and characterized a new strain of SARS
      CoV (strain v2163) that was highly lethal in 5- to 6-week-old BALB/c mice. It had
      nine mutations affecting 10 amino acid residues. Strain v2163 increased IL
      1alpha, IL-6, MIP-1alpha, MCP-1, and RANTES in mice, and high IL-6 expression
      correlated with mortality. The infection largely mimicked human disease, but lung
      pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was
      shown with known inhibitors of SARS-CoV replication. In v2163-infected mice,
      Ampligen was fully protective, stinging nettle lectin (UDA) was partially
      protective, ribavirin was disputable and possibly exacerbated disease, and
      EP128533 was inactive. Ribavirin, UDA, and Ampligen decreased IL-6 expression.
      Strain v2163 provided a valuable model for anti-SARS research.

PMID- 19853274
TI  - Advanced oxidation and reduction process chemistry of methyl tert-butyl ether
      (MTBE) reaction intermediates in aqueous solution: 2-methoxy-2-methyl-propanal, 2
      methoxy-2-methyl-propanol, and 2-methoxy-2-methyl-propanoic acid.
AB  - Absolute rate constants for the reaction of three important degradation products
      of methyl-tert-butyl ether (MTBE) with the hydroxyl radical, hydrated electron
      and hydrogen atom were determined in aqueous solution at room temperature. These
      three intermediate species; 2-methoxy-2-methyl propanal (MMP), 2-methoxy-2-methyl
      propanol (MMP-OH) and 2-methoxy-2-methyl-propionic acid (MMP-acid), are formed in
      the degradation of MTBE under advanced oxidation and reduction process
      conditions. The rate constants for their hydroxyl radical oxidation of (3.99+/
      0.29)x10(9), (8.02+/-0.53)x10(8), and (7.73+/-0.48)x10(8)M(-1)s(-1),
      respectively, show that this reaction would be the overall dominant degradation
      pathway for these three compounds, relative to their corresponding hydrated
      electron reduction values of (3.11+/-0.32)x10(7), (7.8+/-1.8)x10(6) and (1.40+/
      0.10)x10(9)M(-1)s(-1), and hydrogen atom rate constants of (1.65+/-0.14)x10(7),
      (1.30+/-0.13) x10(8) and <1.2 x 10(6)M(-1)s(-1).

PMID- 19853275
TI  - Degradation and adsorption of selected pharmaceuticals and personal care products
      (PPCPs) in agricultural soils.
AB  - Pharmaceuticals and personal care products (PPCPs) are emerging contaminants in
      the environment, which have drawn popular concerns recently. Most studies on the
      environmental fate of PPCPs have focused on their behaviors during wastewater
      treatment processes, in aquatic environments, and in the sludge, however, little
      is known about their behavior in agricultural soils. In this study, adsorption
      and degradation of six selected PPCPs, including clofibric acid, ibuprofen,
      naproxen, triclosan, diclofenac and bisphenol A have been investigated in the
      laboratory using four US agricultural soils associated with reclaimed wastewater
      reuse. Adsorption test using a batch equilibrium method demonstrated that
      adsorption of all tested chemicals in soils could be well described with
      Freundlich equation, and their adsorption affinity on soil followed the order of
      triclosan>bisphenol A>clofibric acid>naproxen>diclofenac>ibuprofen. Retardation
      factor (R(F)) suggested that ibuprofen had potential to move downward with
      percolating water, while triclosan and bisphenol A were readily retarded in
      soils. Degradation of selected PPCPs in soils generally followed first-order
      exponential decay kinetics, with half-lives ranging from 0.81 to 20.44 d.
      Degradation of PPCPs in soils appeared to be influenced by the soil organic
      matter and clay contents. Sterilization generally decreased the degradation
      rates, indicating microbial activity played a significant role in the degradation
      in soils. The degradation rate constant decreased with increasing initial
      chemical concentrations in soil, implying that the microbial activity was
      inhibited with high chemical loading levels.

PMID- 19853276
TI  - Coastal sewage discharge and its impact on fish with reference to antibiotic
      resistant enteric bacteria and enteric pathogens as bio-indicators of pollution.
AB  - Presence of antibiotic resistant bacteria as bio-indicators of pollution was
      monitored in fish (colons and gills) and in sewage treated effluent (STE) in two
      marine sites in the Gulf of Oman, Muscat. One site was polluted as the sewage
      effluent STE was directly discharged into the sea while the unpolluted site was
      10 km away. A total of 42 water samples (250 mL each) were collected from both
      sites. In the polluted site, 14 samples were taken directly from the STE
      discharge point and 14 from the surrounding area near the STE discharging point
      (7-10 m). Water and fish samples were collected from polluted and unpolluted
      sites. Chlorine and nitrate levels were significantly higher in STE samples. A
      significant difference (P<0.005) was found in total bacterial count of fish colon
      and gills in the two sites. Most probable number (MPN) was significantly higher
      in STE and polluted seawater over unpolluted. Coliforms were detected in the
      polluted site only. A total of 320 target enteric normal flora of animals and
      pathogenic species were isolated from 10 genera taken from water and fish
      samples. The isolates were exposed to 14 antibiotics. Most of the isolates were
      resistant to at least one antibiotic with ampicillin was the dominant antibiotic.
      This is a clear indication that sewage effluent causes contamination of marine
      wildlife along coastal lines.

PMID- 19853277
TI  - Cumulative and residual effects of de-oiled two-phase olive mill waste
      application to soil on diuron sorption, leaching, degradation, and persistence.
AB  - Laboratory and field experiments were conducted to evaluate the influence of de
      oiled two-phase olive mill waste (DTPOMW) amendments on the sorption-desorption,
      degradation, leaching, and persistence of the herbicide diuron in a
      representative olive grove soil. The soil was amended in the laboratory with
      DTPOMW at the rates of 5% and 10% (w/w), and in the field with 27 and 54 Mg ha(
      1) of DTPOMW for 7 years. Cumulative and residual effects were evaluated in the
      last year and 2 years after the last DTPOMW field application (2005 and 2007,
      respectively). The results showed that the adsorption of diuron to the soil
      significantly increased in the presence of DTPOMW in the laboratory and field
      amended soils, and that humic acid content was mainly responsible for this
      increase. The DTPOMW soil application only significantly increased the half-life
      of diuron in the laboratory-amended soils, ranging from 8.6d for the original
      soil to 51 d at the greater application rate. The DTPOMW amendments significantly
      reduced the downward mobility of diuron, and reduced the amount of herbicide
      leached in the laboratory and field-amended soils, and no residues of diuron were
      detected in the leacheate of the residual-amended columns. In the field study,
      DTPOMW addition increased the persistence of diuron in the upper 10 and 5 cm of
      the soils in the cumulative and residual years, respectively, decreasing the
      herbicide's vertical movement through the amended soils with increasing DTPOMW
      rate. This study has shown that in olive grove soils DTPOMW amendment may be an
      effective management practice for controlling ground water contamination by
      diuron.

PMID- 19853278
TI  - Out of the North Sea: the Zeeland ridges Neandertal.
AB  - In 2001, a portion of human frontal bone was discovered in sediments extracted
      from the bottom of the North Sea, 15km off the coast of the Netherlands. The
      extraction zone is located in the so-called Zeeland Ridges area located at 51
      degrees 40' northern latitude and 3 degrees 20' eastern longitude. The specimen
      was dredged up from sediments containing Late Pleistocene faunal remains and
      Middle Palaeolithic artefacts, including well-finished small handaxes and
      Levallois flakes. The details of the supraorbital morphology, as well as the
      quantitative assessment of the shape of the external surface of the squama using
      traditional and 3D geometric morphometrics, unambiguously assign the Zeeland
      Ridges frontal bone to Homo neanderthalensis. Carbon and nitrogen isotopic
      analysis indicate that the Zeeland Ridges hominin, like other Neandertals, was
      highly carnivorous and does not show evidence for the consumption of aquatic
      foods. A lesion on the outer table and diploic layer of the bone in the area of
      the supratoral sulcus can be interpreted as the result of an intradiploic
      epidermoid cyst, a type of neoplasm diagnosed for the first time in Neandertal
      remains. So far, the Zeeland Ridges Neandertal is the first Pleistocene fossil
      hominin found under seawater and the first recorded in the Netherlands.

PMID- 19853279
TI  - The distribution of depleted uranium contamination in Colonie, NY, USA.
AB  - Uranium oxide particles were dispersed into the environment from a factory in
      Colonie (NY, USA) by prevailing winds during the 1960s and '70s. Uranium
      concentrations and isotope ratios from bulk soil samples have been accurately
      measured using inductively coupled plasma quadrupole mass spectrometry (ICP-QMS)
      without the need for analyte separation chemistry. The natural range of uranium
      concentrations in the Colonie soils has been estimated as 0.7-2.1 microg g(-1),
      with a weighted geometric mean of 1.05 microg g(-1); the contaminated soil
      samples comprise uranium up to 500+/-40 microg g(-1). A plot of (236)U/(238)U
      against (235)U/(238)U isotope ratios describes a mixing line between natural
      uranium and depleted uranium (DU) in bulk soil samples; scatter from this line
      can be accounted for by heterogeneity in the DU particulate. The end-member of DU
      compositions aggregated in these bulk samples comprises (2.05+/-0.06) x 10(
      3)(235)U/(238)U, (3.2+/-0.1)x10(-5)(236)U/(238)U, and (7.1+/-0.3) x 10(
      6)(234)U/(238)U. The analytical method is sensitive to as little as 50 ng g(-1)
      DU mixed with the natural uranium occurring in these soils. The contamination
      footprint has been mapped northward from site, and at least one third of the
      uranium in a soil sample from the surface 5 cm, collected 5. 1km NNW of the site,
      is DU. The distribution of contamination within the surface soil horizon follows
      a trend of exponential decrease with depth, which can be approximated by a simple
      diffusion model. Bioturbation by earthworms can account for dispersal of
      contaminant from the soil surface, in the form of primary uranium oxide
      particulates, and uranyl species that are adsorbed to organic matter. Considering
      this distribution, the total mass of uranium contamination emitted from the
      factory is estimated to be c. 4.8 tonnes.

PMID- 19853280
TI  - Ambient temperature and mortality: an international study in four capital cities
      of East Asia.
AB  - Extreme ambient temperature has been associated with increased daily mortality
      across the world. We describe the ambient temperature-mortality association for
      four capital cities in East Asia, Seoul, Beijing, Tokyo, and Taipei, and identify
      a threshold temperature for each city and the percent increase in mortality. We
      adapted generalized linear modeling with natural cubic splines (GLM+NS) to
      examine the association between daily mean apparent temperature (AT) and total
      mortality, as well as mortality due to respiratory (RD) and cardiovascular (CVD)
      causes in a threshold model. We conducted a time-series analysis adjusting for
      day of the week and long-term time trend. The study period differed by city. The
      threshold temperature for all seasons was estimated to be 30.1-33.5 degrees C,
      31.3-32.3 degrees C, 29.4-30.8 degrees C, and 25.2 degrees -31.5 degrees C for
      Seoul, Beijing, Tokyo, and Taipei, respectively, on the same day. For the mean
      daily AT increase of 1 degrees C above the thresholds in Seoul, Tokyo, and
      Taipei, estimated percentage increases in daily total mortality were 2.7 (95%
      confidence interval (CI)=2.2-3.1), 1.7 (95% CI=1.5-2.0), and 4.3 (95% CI=2.9
      5.7), respectively. Beijing provided no total mortality counts. Estimated
      percentage increases were 2.7-10.5 for RD mortality, 1.1-9.3 for CVD mortality in
      4 cities. This study identified increased mortality due to exposure to elevated
      AT. The importance of effects of AT and city-specific threshold temperatures
      suggests that analyses of the impact of climate change should take regional
      differences into consideration.

PMID- 19853281
TI  - Differentiation in the fertility of Inceptisols as related to land use in the
      upper Solimoes river region, western Amazon.
AB  - The Upper Solimoes river region, western Amazon, is the homeland of indigenous
      populations and contains small-scale agricultural systems that are important for
      biodiversity conservation. Although traditional slash-and-burn agriculture is
      being practiced over many years, deforestation there is relatively small compared
      to other Amazon regions. Pastures are restricted to the vicinity of cities and do
      not spread to the small communities along the river. Inceptisols are the main
      soil order (>90%) in the area and have unique attributes including high Al
      content and high cation exchange capacity (CEC) due to the enrichment of the clay
      fraction with 2:1 secondary aluminosilicates. Despite its importance, few studies
      have focussed on this soil order when considering land use effects on the
      fertility of Amazon soils. Thus, the objective of this study was to evaluate
      changes in soil fertility of representative land use systems (LUSs) in the Upper
      Solimoes region, namely: primary rainforest, old secondary forest, young
      secondary forest, agroforestry, pasture and agriculture. LUSs were significantly
      differentiated by the chemical attributes of their topsoil (0-20 cm). Secondary
      forests presented soil chemical attributes more similar to primary rainforest
      areas, while pastures exhibited the highest dissimilarity from all the other
      LUSs. As a whole, soil chemical changes among Inceptisols dominated LUSs showed
      patterns that were distinct from those reported from other Amazon soils like
      Oxisols and Ultisols. This is probably related to the presence of high-activity
      clays enriched in exchangeable aluminum that heavily influenced the soil chemical
      reactions over the expected importance of organic matter found in most studies
      conducted over Oxisol and Ultisol.

PMID- 19853282
TI  - Maternal levels of organochlorines in two communities in southern Vietnam.
AB  - Some pesticides and PCBs continue to be reported as environmental problems in
      some areas of Vietnam. In 2005, a study among delivering women took place in two
      communities in south-central Vietnam (Khanh Hoa Province), namely the coastal
      city of Nha Trang and the rural district of Dien Khanh located about 10 km
      inland. The main findings in plasma (n=189) were relatively high mean
      concentrations of p,p'-DDE (12.2 microg/l in Nha Trang and 11.4 microg/l in Dien
      Khanh) and p,p'-DDT (1.2 microg/l in Nha Trang and 1.1 microg/l in Dien Khanh)
      with no significant community differences. The ratio of p,p'-DDE/p,p'-DDT (11.5
      in Nha Trang/12.7 in Dien Khanh) suggests, as in other Vietnamese OCs studies, a
      relatively recent use of this pesticide. Mean concentrations of PCB 153 (0.15
      microg/l in Nha Trang and 0.10 microg/l in Dien Khanh) and other congeners were
      low in both communities. Age and parity (all compounds), as well as community of
      residence for PCB 153, were the most important predictors of plasma OCs
      concentrations.

PMID- 19853283
TI  - Connexin 43 gene expression in male and female gonads of porcine offspring
      following in utero exposure to an anti-androgen, flutamide.
AB  - The aim of this study was to show the effect of maternal exposure to flutamide on
      connexin 43 (Cx43) gene expression in testes and ovaries of 2-day-old piglets.
      Additionally, anogenital distance (AGD) was measured both in male and female
      offspring. Immunohistochemistry, Western blotting, and RT-PCR were performed to
      assess the immunoreactivity and the presence of Cx43 protein and it's mRNA,
      respectively. Following flutamide exposure strong immunostaining for Cx43 was
      observed between testicular Leydig cells, between granulosa cells of primary
      follicles, and between interstitial cells surrounding clusters of oocyte nests in
      the ovarian cortex as in the respective controls. Differences between the
      flutamide-treated groups and the controls obtained by qualitative
      immunohistochemistry were confirmed by quantitative image analysis (*P<0.05;
      **P<0.01). In Western blotting, Cx43 appeared as a band of 43kDa, whereas
      electrophoresis revealed PCR products of the predicted sizes. Screening for Cx43
      expression revealed the presence of a transcript, both in control and in
      flutamide-treated pigs. The AGD values differed significantly from the control
      (*P<0.05). Overall, since no obvious changes in gonad morphology were observed
      and the Cx43 signal was present in all the examined tissues, it seems likely that
      androgens acting through ARs are not involved in the control of Cx43 gene
      expression in neonatal pig gonads.

PMID- 19853284
TI  - Cellular localization of aquaporins along the secretory pathway of the lactating
      bovine mammary gland: an immunohistochemical study.
AB  - In this study we examined the cellular localization of aquaporins (AQPs) along
      the secretory pathway of actively lactating bovine mammary glands using
      immunohistochemistry. Mammary tissues examined included secretory ducts and
      acini, gland cisterns, teats, stromal and adipose tissues. Aquaporin 1 (AQP1) was
      localized in capillary endothelia throughout the mammary gland in addition to
      myoepithelial cells underlying teat duct epithelia. AQP2 and AQP6 were not
      detected and AQP9 was found only in leukocytes. AQP3 and AQP4 were observed in
      selected epithelial cells in the teat, cistern and secretory tubuloalveoli. AQP5
      immunopositivity was prominent in the cistern. AQP3 and AQP7 were found in smooth
      muscle bundles in the teat, secretory epithelial cells and duct epithelial cells.
      These immunohistochemical findings support a functional role for aquaporins in
      the transport of water and small solutes across endothelial and epithelial
      barriers in the mammary gland and in the production and secretion of milk.

PMID- 19853285
TI  - PRDM16 expression in the developing mouse embryo.
AB  - PRDM16 is a member of the PR domain-containing protein family and is associated
      with various disease states including myelodysplastic syndrome and adult T-cell
      leukemia, as well as developmental abnormalities such as cleft palate. It is also
      known to act as a regulator of cell differentiation. Expression analysis of
      PRDM16 is limited, especially within the developing embryo. The current study
      evaluated the temporal and spatial localization of PRDM16 during early mouse
      development (embryonic days 8.5-14.5). PRDM16 was first detected on E9.5 in a
      limited number of tissues and by E14.5, was expressed in a broad range of
      developing tissues including those of the brain, lung, kidney, and
      gastrointestinal tract. The expression pattern is consistent with a role for
      PRDM16 in the development of multiple tissues. Collectively, these studies are
      the first to characterize the expression of the PRDM16 gene during early murine
      development.

PMID- 19853286
TI  - AKT1 pleckstrin homology domain E17K activating mutation in endometrial
      carcinoma.
AB  - OBJECTIVES: The PI3K/AKT pathway is frequently activated in endometrial carcinoma
      (EC) mainly due to mutations in the PIK3CA and PTEN genes. These events are
      common and believed to be the key to endometrial carcinogenesis. Recently, a
      somatic activating mutation in the AKT1 gene (E17K) was identified in several
      cancer types. In this study we explored the frequency of this AKT1 mutation in
      endometrial carcinoma. METHODS: Tumor DNA, extracted from 73 EC was analyzed for
      AKT1 E17K mutation (G49A) using matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF MS). In addition, the tumors were screened
      for coexisting common mutations in PTEN, PIK3CA and KRAS. RESULTS: The AKT1 E17K
      mutation was detected in 4% of EC. One of the AKT1-mutated tumors showed
      coexisting PTEN loss-of-function mutation. CONCLUSION: We identified the AKT1
      E17K mutation in 4% of endometrial carcinomas. The presence of double AKT1/ PTEN
      mutants is in accord with the hypothesis that in EC more than one hit is required
      to completely activate the PI3K pathway. Furthermore, AKT1 mutations were limited
      to high grade, advanced stage tumors suggesting that this mutation confers a more
      aggressive tumor behavior.

PMID- 19853288
TI  - Architecture-dependent noise discriminates functionally analogous differentiation
      circuits.
AB  - Gene regulatory circuits with different architectures (patterns of regulatory
      interactions) can generate similar dynamics. This raises the question of why a
      particular circuit architecture is selected to implement a given cellular
      process. To investigate this problem, we compared the Bacillus subtilis circuit
      that regulates differentiation into the competence state to an engineered circuit
      with an alternative architecture (SynEx) in silico and in vivo. Time-lapse
      microscopy measurements showed that SynEx cells generated competence dynamics
      similar to native cells and reconstituted the physiology of differentiation.
      However, architectural differences between the circuits altered the dynamic
      distribution of stochastic fluctuations (noise) during circuit operation. This
      distinction in noise causes functional differences between the circuits by
      selectively controlling the timing of competence episodes and response of the
      system to various DNA concentrations. These results reveal a tradeoff between
      temporal precision and physiological response range that is controlled by
      distinct noise characteristics of alternative circuit architectures.

PMID- 19853287
TI  - Prognostic factors for response to cisplatin-based chemotherapy in advanced
      cervical carcinoma: a Gynecologic Oncology Group Study.
AB  - PURPOSE: Cisplatin-based combination chemotherapy is considered standard
      treatment for advanced/recurrent cervical carcinoma; however, the majority of
      patients do not respond. This study was undertaken to identify the prognostic
      factors and develop a model predictive of (non-) response to chemotherapy.
      METHODS: Four-hundred twenty-eight patients with advanced cervical cancer who
      received a cisplatin-containing combination in three Gynecologic Oncology Group
      (GOG) protocols (110, 169 and 179) were evaluated for baseline clinical
      characteristics and multivariate analysis was conducted to identify factors
      independently prognostic predictive of response using a Logistic regression
      model. A predictive model was developed and externally validated using an
      independent GOG protocol (149) data. RESULTS: Multivariate analysis identified
      five factors (African-American, performance status [PS] >0, pelvic disease, prior
      radiosensitizer and time interval from diagnosis to first recurrence <1 year)
      independently prognostic of poor response. A simple prognostic index was derived
      based on the total number of risk factors. When patients were classified into
      three risk groups (low risk: 0-1 factor; mid risk: 2-3 factors; high risk: 4-5
      factors), patients with 4-5 risk factors were estimated to have a response rate
      of only 13%, and median progression-free and overall survival of 2.8 months and
      5.5 months, respectively. The accuracy of the index was supported by both
      internal and external datasets. CONCLUSIONS: A simple index based on five
      prognostic factors may have utility in clinical practice to identify the women
      who are not likely to respond to the cisplatin-containing regimens. This subgroup
      of patients should be considered for non-cisplatin chemotherapy or
      investigational trials.

PMID- 19853289
TI  - Embryo production after in vitro fertilization with frozen-thawed, sex-sorted, re
      frozen-thawed bull sperm.
AB  - The objective of this study was to determine the in vitro fertilizing capacity of
      bull sperm derived from fresh or frozen samples and subjected to sex sorting and
      re-cryopreservation. Four sperm types were assessed for their ability to
      fertilize and sustain early embryo development in vitro. Semen from three Bos
      taurus bulls of different breeds (Jersey, Holstein and Simmental) was collected
      and either sorted immediately and then frozen (SF) or frozen for later sorting.
      Frozen sperm destined for sorting were thawed, sex-sorted, and re-frozen (FSF) or
      thawed, sex-sorted (FS), and used immediately for in vitro fertilization (IVF).
      Frozen-thawed nonsorted semen from the same ejaculate was used as a control.
      Oocytes from donor cows were aspirated via ovum pick-up and matured in vitro
      prior to IVF and culture. On average, 19.0+/-1.7 (mean+/-SEM) oocytes were
      aspirated per donor cow, of which 74.4+/-2.2% were selected for maturation. The
      proportion of cleaved embryos (Day 3) did not differ between sperm groups
      (P=0.91). Likewise, IVF with FSF sperm resulted in similar Day 7 blastocyst rates
      (as a percentage of total oocytes) as those of control, SF, and FS sperm (FSF,
      34.5+/-4.7; control, 32.2+/-4.6; SF, 35.9+/-4.8; and FS, 26.9+/-4.1%; P=0.23).
      These encouraging results show that frozen-thawed sex-sorted sperm may be re
      frozen and used for in vitro embryo production with similar blastocyst production
      as that of nonsorted frozen-thawed and sex-sorted frozen-thawed sperm.

PMID- 19853290
TI  - Word order and Broca's region: evidence for a supra-syntactic perspective.
AB  - It has often been suggested that the role of Broca's region in sentence
      comprehension can be explained with reference to general cognitive mechanisms
      (e.g. working memory, cognitive control). However, the (language-related) basis
      for such proposals is often restricted to findings on English. Here, we argue
      that an extension of the database to other languages can shed new light on the
      types of mechanisms that an adequate account of Broca's region should be equipped
      to deal with. This becomes most readily apparent in the domain of word order
      variations, which we examined in German verb-final sentences using event-related
      fMRI. Our results showed that activation in the pars opercularis--a core
      subregion of Broca's area--was not only modulated by the relative ordering of
      subject and object, but also by a further factor known to affect word order in a
      number of languages, namely referentiality. Notably, the finding provides the
      first demonstration of a word order-related activation difference within subject
      initial sentences in this region. Additional parametric analyses using individual
      behavioral data as predictors further attest to the independence of the pars
      opercularis activation from: (a) sentence acceptability, and (b) difficulty in
      performing the experimental (judgment) task. We argue that these and related
      findings attest to the need for a processing mechanism that can manipulate
      predicate-independent, interacting and hierarchically structured relational
      representations during real time comprehension. These properties pose a challenge
      to existing accounts of pars opercularis function.

PMID- 19853291
TI  - Metal intracellular partitioning as a detoxification mechanism for mummichogs
      (Fundulus heteroclitus) living in metal-polluted salt marshes.
AB  - Intracellular partitioning of trace metals is critical to metal detoxification in
      aquatic organisms. In the present study, we assessed metal (Cd, Cu, Pb, and Zn)
      handling capacities of mummichogs (Fundulus heteroclitus) in metal-polluted salt
      marshes in New York, USA by examining metal intracellular partitioning. Despite
      the lack of differences in the whole body burdens, partitioning patterns of
      metals in intracellular components (heat-stable proteins, heat-denaturable
      proteins, organelles, and metal-rich granules) revealed clear differential metal
      handling capacities among the populations of mummichogs. In general, mummichogs
      living in metal-polluted sites stored a large amount of metals in detoxifying
      cellular components, particularly metal-rich granules (MRG). Moreover, only
      metals associated with MRG were consistently correlated with variations in the
      whole body burdens. These findings suggest that metal detoxification through
      intracellular partitioning, particularly the sequestration to MRG, may have
      important implications for metal tolerance of mummichogs living in chronically
      metal-polluted habitats.

PMID- 19853292
TI  - Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to
      the brain.
AB  - Trimethylated chitosan (TMC) surface-modified poly(d,l-lactide-co-glycolide)
      (PLGA) nanoparticles (TMC/PLGA-NP) were synthesized as a drug carrier for brain
      delivery. TMC was covalently coupled to the surface of PLGA nanoparticles (PLGA
      NP) via a carbodiimide-mediated link. The zeta potential of TMC/PLGA-NP was about
      20mV with a mean diameter around 150nm. 6-coumarin loaded PLGA-NP and TMC/PLGA-NP
      were injected into the caudal vein of mice, and fluorescent microscopy of brain
      sections showed a higher accumulation of TMC/PLGA-NP in the cortex, paracoele,
      the third ventricle and choroid plexus epithelium, while no brain uptake of PLGA
      NP was observed. There was no pronounced difference in cell viability between
      TMC/PLGA-NP and PLGA-NP as shown by MTT assay. Behavioral testing showed that the
      injection of coenzyme Q(10) loaded TMC/PLGA-NP greatly improved memory
      impairment, restoring it to a normal level, but the efficacy was slight for
      loaded PLGA-NP, without TMC conjugation. The senile plaque and biochemical
      parameter tests confirmed the brain-targeted effects of TMC/PLGA-NP. These
      experiments show that TMC surface-modified nanoparticles are able to cross the
      blood-brain barrier and appear to be a promising brain drug delivery carrier with
      low toxicity.

PMID- 19853293
TI  - The exploitation of differential endocytic pathways in normal and tumor cells in
      the selective targeting of nanoparticulate chemotherapeutic agents.
AB  - Polymeric micelles with cross-linked ionic cores of poly(methacrylic acid) and
      nonionic shell of poly(ethylene oxide) (cl-micelles) are shown here to readily
      internalize in epithelial cancer cells but not in normal epithelial cells that
      form tight junctions (TJ). The internalization of such cl-micelles in the cancer
      cells proceeded mainly through caveolae-mediated endocytosis. In confluent normal
      epithelial cells this endocytosis route was absent at the apical side and the cl
      micelles sequestered in TJ regions of the cell membrane without entering the
      cells for at least 24h. Disruption of the TJ by calcium deprivation resulted in
      redistribution of cl-micelles inside the cells. In cancer cells following initial
      cellular entry the cl-micelles bypassed the early endosomes and reached the
      lysosomes within 30min. This allowed designing cl-micelles with cytotoxic drug,
      doxorubicin, linked via pH-sensitive hydrazone bonds, which were cleaved in the
      acidic environment of lysosomes resulting in accumulation of the drug in the
      nucleus after 5h. Such pH-sensitive cl-micelles displayed selective toxicity to
      cancer cells but were non-toxic to normal epithelial cells. In conclusion, we
      describe major difference in interactions of cl-micelles with cancer and normal
      cells that can lead to development of novel drug delivery system with reduced
      side effects and higher efficacy in cancer chemotherapy.

PMID- 19853294
TI  - Myogenic differentiation of human bone marrow mesenchymal stem cells on a 3D nano
      fibrous scaffold for bladder tissue engineering.
AB  - Current strategies for engineering bladder tissues include a bladder biopsy for
      in vitro cell expansion for use in reconstructive procedures. However, this
      approach cannot be used in patients with bladder cancer who need a complete
      bladder replacement. Bone marrow mesenchymal stem cells (BMSC) might be an
      alternative cell source to better meet this need. We investigated the effects of
      soluble growth factors, bladder extracellular matrix (ECM), and 3D dynamic
      culture on cell proliferation and differentiation of human BMSC into smooth
      muscle cells (SMC). Myogenic growth factors (PDGF-BB and TGF-beta1) alone, or
      combined either with bladder ECM or dynamic cultures, induced BMSC to express
      smooth muscle-specific genes and proteins. Either ECM or the dynamic culture
      alone promoted cell proliferation but did not induce myogenic differentiation of
      BMSC. A highly porous poly-l-lactic acid (PLLA) scaffold provided a 3D structure
      for maximizing the cell-matrix penetration, maintained myogenic differentiation
      of the induced BMSC, and promoted tissue remolding with rich capillary formation
      in vivo. Our results demonstrate that myogenic-differentiated BMSC seeded on a
      nano fibrous PLLA scaffold can be potentially used for cell-based tissue
      engineering for bladder cancer patients requiring cystoplasty.

PMID- 19853295
TI  - Biomaterial mediated epithelial-mesenchymal interaction of salivary tissue under
      serum free condition.
AB  - Many organs develop from epithelial-mesenchymal interactions such that in order
      to regenerate these organs, it might be a preferable strategy to recapitulate
      this process. However, in the current culture system designed for tissue
      interaction, the supplement of serum is required. The aim of this study is to
      explore the possibility of reproducing epithelial-mesenchymal interaction and
      ensuing morphogenesis in a serum-free condition. In accordance with the previous
      studies, by using a standard model of murine fetal submandibular gland (SMG), the
      tissue interaction and the morphogenesis were largely dependent on serum.
      Nonetheless, when tissue recombinants were cultivated on polyvinylidene fluoride
      (PVDF), but not on other biomaterials, the serum-deprived effect could be
      rescued. On PVDF, SMG tissue recombinant was able to increase epithelial size, de
      novo synthesize basement membrane, and develop new branches without serum.
      Although the gene expression levels of selected morphogens were not significantly
      altered, the precise localization of morphogenetic-decisive extracellular matrix
      such as type III collagen and the superior adsorbing capacity of essential
      diffusible factors like fibroblast growth factor 7 (FGF7) might account for PVDF
      effect. Accordingly, the result demonstrates that it is possible to establish a
      serum-free system that is competent in facilitating epithelial-mesenchymal
      interaction of salivary tissue. With PVDF, the crosstalk between SMG epithelia
      and mesenchyme could be sustained without serum.

PMID- 19853297
TI  - A collagen-mimetic triple helical supramolecule that evokes integrin-dependent
      cell responses.
AB  - Collagen is an abundantly distributed extracellular matrix protein in mammalian
      bodies that maintains structural integrity of the organs and tissues. Besides its
      function as a structural protein, collagen has various biological functions which
      regulate cell adhesion, migration and differentiation. In order to develop
      totally synthetic collagen-surrogates, we recently reported a basic concept for
      preparing collagen-like triple helical supramolecules based on the self-assembly
      of staggered trimeric peptides with self-complementary shapes. In this paper, we
      add one of the specific cellular functions of the native collagen to the collagen
      mimetic supramolecule. We synthesized a self-assembling peptide unit containing
      the integrin-binding sequence Gly-Phe-Hyp-Gly-Glu-Arg. The supramolecule carrying
      the sequence exhibited significant binding activity to human dermal fibroblasts.
      The supramolecular structure was found to be essential for function in in vitro
      cell culture. Cell adhesion was shown to be comparable to that of native
      collagen, and was further demonstrated to be mediated solely by integrin alpha 2
      beta 1. Well-grown focal contacts and stress fibers were observed in cells spread
      on the supramolecular collagen-mimetic. The results demonstrate the potential of
      peptide-based artificial collagen as a biomaterial for regulating specific
      cellular function and fate.

PMID- 19853298
TI  - The proprotein convertase furin in human trophoblast: Possible role in promoting
      trophoblast cell migration and invasion.
AB  - Furin, a proprotein convertase (PC), is ubiquitously expressed and implicated in
      many physiological and pathological processes. This study is aimed to identify
      the role of furin in human trophoblast invasion and migration. Furin was found to
      be highly expressed in placental villi of both rhesus monkeys and human beings
      during early pregnancy. Specifically, furin was found in trophoblast column and
      trophoblast shell, regions where highly invasive cytotrophoblast cells invade the
      maternal decidua during human placentation. To determine whether furin plays any
      role in trophoblast invasion and migration, we employed human extravillous
      HTR8/SVneo cells in Matrigel invasion and transwell migration assays. Knocking
      down furin expression by siRNA significantly inhibited invasion and migration of
      HTR8/SVneo cells (P<0.01), with corresponding decrease of matrix
      metalloproteinase-9 (MMP-9) activities. In contrast, over-expression of furin
      markedly increased cell invasion and migration (P<0.01), accompanied by
      significant increase of MMP-9 activities. Furthermore, furin siRNA significantly
      increased the levels of both tissue inhibitors of MMPs (TIMP)-1 and -2. Our
      results suggest that furin may play an important role in the invasion and
      migration of human trophoblast cells during early pregnancy.

PMID- 19853296
TI  - Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced
      ocular wounds.
AB  - Half mustard (CEES) and nitrogen mustard (NM) are commonly used surrogates and
      vesicant analogs of the chemical warfare agent sulfur mustard. In the current
      study, in situ forming poly(ethylene glycol) (PEG)-based doxycycline hydrogels
      are developed and evaluated for their wound healing efficacy in CEES and NM
      exposed rabbit corneas in organ culture. The hydrogels, characterized by UV-Vis
      spectrophotometry, rheometry, and swelling kinetics, showed that the hydrogels
      are optically transparent, have good mechanical strength and a relatively low
      degree of swelling (<7%). In vitro doxycycline release from the hydrogel disks
      (0.25% w/v) was found to be biphasic with release half times of approximately 12
      and 72h, respectively, with 80-100% released over a 7-day period. Permeation of
      doxycycline through vesicant wounded corneas was found to be 2.5 to 3.4 fold
      higher than non-wounded corneas. Histology and immunofluorescence studies showed
      a significant reduction of matrix metalloproteinase-9 (MMP-9) and improved
      healing of vesicant-exposed corneas by doxycycline hydrogels compared to a
      similar dose of doxycycline delivered in phosphate buffered saline (PBS, pH 7.4).
      In conclusion, the current studies demonstrate that the doxycycline-PEG hydrogels
      accelerate corneal wound healing after vesicant injury offering a therapeutic
      option for ocular mustard injuries.

PMID- 19853299
TI  - p53 Mediates epidermal growth factor (EGF) induction of MMP-2 transcription and
      trophoblast invasion.
AB  - Trophoblast invasion is a highly restricted process, regulated by growth factors,
      hormones and cytokines. Trophoblast invasion is attainable due to proteolytic
      degradation of the epithelial basement membrane and the extracellular matrix by
      proteolytic enzymes like the matrix metalloproteinases (MMPs) particularly MMP-2.
      Epidermal growth factor (EGF), a major mediator of implantation, has been
      documented to induce MMP-2 and trophoblast invasion. The aim of this study was to
      investigate the transcriptional regulation of MMP-2 in EGF- stimulated invasive
      trophoblast cells, using JAR choriocarcinoma cell line and 6-8w 1st trimester
      trophoblasts. MMP-2 expression was induced by EGF within 1 hour. Gelshift and
      supershift assay were used to explore transcription factors involved in MMP-2
      regulation. EGF induced binding activity and expression of phophorylated p53, AP
      2alpha and -gamma, C/EBPepsilon and -lambda to their responding sequences, found
      in the MMP-2 promoter. Additionally EGF induced binding activity to SP-1, but
      reduced the expression of SP-1 and SP-4. Inhibition of p53 by antisense reduced
      both basic and EGF- induced MMP-2 expression. In summary: MMP-2 transcriptional
      regulation by EGF in invasive trophoblasts is mediated through several binding
      sites and transcription factors including p53, AP-2alpha and -gamma, C/EBPepsilon
      and -lambda and SP-1. p53 mediates both basic and EGF-induced MMP-2
      transcription.

PMID- 19853300
TI  - Gross abnormalities of the umbilical cord: related placental histology and
      clinical significance.
AB  - OBJECTIVE: To evaluate umbilical cord abnormalities predisposing to mechanical
      cord compression and determine their relationship to adverse clinical outcomes
      and stasis-associated histologic changes in the placenta. METHODS: Placental
      slides of 224 singleton pregnancies with gross cord abnormality (true knots, long
      cords, nuchal/body cords, abnormal cord insertion, hypercoiled cords, narrow
      cords with diminished Wharton's jelly), delivered on or after 28 weeks
      gestational age, and 317 gestational age-matched controls, were reviewed and
      specifically evaluated for the following histologic changes: (1) fetal vascular
      ectasia, (2) fetal vascular thrombosis, (3) and fetal thrombotic
      vasculopathy/avascular villi. These changes were analyzed in relation to both
      clinical information and findings at gross pathologic examination. RESULTS: Gross
      cord abnormalities were associated with stillbirth, intrauterine growth
      restriction, non-reassuring fetal tracing, meconium-stained amniotic fluid, and
      increased rate of emergency Cesarean section. At microscopic evaluation, cases
      with gross cord abnormalities showed a statistically significant association with
      both ectasia and thrombosis in the fetal vasculature, as well as changes of fetal
      thrombotic vasculopathy in the terminal villi. When considering individual gross
      cord abnormalities, long cord and nuchal cord had the highest rates of thrombosis
      related histopathology. Finally, cases with both abnormal cords and histologic
      thrombosis had significantly higher rates of adverse outcomes, including IUGR and
      stillbirth. CONCLUSION: Gross cord abnormalities predispose the fetus to stasis
      induced vascular ectasia and thrombosis, thus leading to vascular obstruction and
      adverse neonatal outcome, including IUGR and stillbirth. We recommend a thorough
      histopathologic evaluation of all placentas with gross cord abnormalities
      predisposing to cord compression.

PMID- 19853301
TI  - ISPCAN Child Abuse Screening Tools Retrospective version (ICAST-R): Delphi study
      and field testing in seven countries.
AB  - OBJECTIVES: To gain consensus among an ethnically and linguistically diverse
      group of international child protection experts on the structure and content of a
      new survey tool for retrospective measurement of child abuse, and to determine
      the performance of the instrument through an international field trial with young
      adults. METHODS: The questionnaire was developed through focus group discussions
      with international experts, and then subjected to a Delphi study in two waves to
      determine the perceived importance and translatability of items. The resultant
      questionnaire was translated into six languages and field tested in seven
      countries with convenient samples of young adults aged 18-26 years (N=842).
      RESULTS: Child maltreatment experts from 28 countries provided input to
      questionnaire development. Satisfactory agreement on draft item inclusion and
      exclusion and the translatability of items was gained. The tool includes 15
      primary questions about potentially abusive physical, sexual and emotional
      events, with follow-up questions about perpetrator characteristics, frequency of
      acts and periods in childhood when the recalled abuse occurred. The field test
      revealed lifetime prevalence per item usually exceeded 10% (11/15 items; range
      2.1-49.5%). Internal consistency (Cronbach's alpha) was moderate to high for each
      of three item sub-sets (between .61 and .82) and the rates of missing data were
      low (less than 1.5% for 14 of 15 items). The great majority of respondents
      nominated either peer and/or adult perpetrators (between 82.3% and 98.2%
      depending upon the item), and among these, child/adolescent peers and non-family
      adults (including teachers for emotional and physical acts) were nominated often.
      CONCLUSIONS: The ICAST-R is based on consensus from international experts,
      translates clearly and has satisfactory properties for adoption as a survey tool
      to estimate prevalence and describe perpetrators and other contextual aspects of
      child abuse. PRACTICE IMPLICATIONS: This tool can be utilized in a broad range of
      cultures and languages and may contribute to improved research practice. Although
      the core items are limited to just 15 acts of maltreatment, if these behaviorally
      specific questions are adopted as key indicators and incorporated into
      comprehensive local, national or regional surveys, eventually there should be
      greater comparability in survey estimates.

PMID- 19853302
TI  - Evaluation for community-based programs: the integration of logic models and
      factor analysis.
AB  - PURPOSE: To discuss the utility of and value of the use of logic models for
      program evaluation of community-based programs and more specifically, the
      integration of logic models and factor analysis to develop and revise a survey as
      part of an effective evaluation plan. PRINCIPAL RESULTS: Diverse stakeholders
      with varying outlooks used a logic model as a framework to reach agreement on a
      plan for a state-wide evaluation. This evaluation plan utilized a survey of sixth
      grade students, administered before and after exposure to a year-long abstinence
      education program. Components of the logic model were linked to specific survey
      questions. Exploratory factor analysis was then used to assess whether and how
      the questions in the survey fit with the constructs of the model; confirmatory
      factor analysis was used to test the hypothesis that the factors identified in
      the exploratory analysis were consistently represented in the survey. MAJOR
      CONCLUSIONS: A logic model is a tool that engages stakeholders to link evaluation
      instruments more closely to specific program objectives. Thus, stakeholders can
      more closely assess the extent to which project outcomes have been achieved. In
      addition, use of factor analysis in the evaluation process can help the
      stakeholders better understand whether evaluation instruments such as a survey
      adequately assess program effectiveness. Lastly, a logic model process can help
      to achieve consensus among diverse stakeholders, by allowing them to focus on
      objectives that are concrete, measurable, and mutually acceptable.

PMID- 19853303
TI  - Influence of metal ions on thermal aggregation of bovine serum albumin:
      aggregation kinetics and structural changes.
AB  - Metal ions are implicated in protein aggregation processes of several
      neurodegenerative pathologies. In this work the effects of Cu(II) and Zn(II) ions
      on heat-induced structural modifications of bovine serum albumin (BSA) were
      studied, with the aim of delineating the role of these ions in the early stages
      of proteins aggregation kinetics. A joint application of different techniques was
      used. The aggregate growth was followed by dynamic light scattering measurements,
      whereas the conformational changes occurring in the protein structure were
      monitored by Raman and IR spectroscopy. Both in absence and in presence of metal
      ions, heating treatment gave rise to beta-structures to the detriment of alpha
      helix conformation of BSA. The temperature of protein unfolding was not
      sensitively affected by the presence of Zn(II) or Cu(II) ions; on the contrary,
      only Zn(II) ions slightly promoted the heat-induced aggregation of the protein,
      since bigger aggregates were formed in their presence. The different efficacy of
      the Cu(II) and Zn(II) ions in promoting the BSA aggregation were highlighted by
      Raman measurements, assessing the role of His residues in metal binding. A
      distinct polypeptide folding of the two metal-BSA systems takes place, since the
      predominant mode of metal binding depends on metal. In particular, in Zn-BSA the
      metal coordination involves the imidazole N(tau) atom of His which can promote
      inter-molecular cross-linking.

PMID- 19853304
TI  - Structural biology of heme binding in the Staphylococcus aureus Isd system.
AB  - Iron is an absolute requirement for nearly all organisms, but most bacterial
      pathogens are faced with extreme iron-restriction within their host environments.
      To overcome iron limitation pathogens have evolved precise mechanisms to steal
      iron from host supplies. Staphylococcus aureus employs the iron-responsive
      surface determinant (Isd) system as its primary heme-iron uptake pathway.
      Hemoglobin or hemoglobin-haptoglobin complexes are bound by Near iron-Transport
      (NEAT) domains within cell surface anchored proteins IsdB or IsdH. Heme is
      stripped from the host proteins and transferred between NEAT domains through IsdA
      and IsdC to the membrane transporter IsdEF for internalization. Once
      internalized, heme can be degraded by IsdG or IsdI, thereby liberating iron for
      the organism. Most components of the Isd system have been structurally
      characterized to provide insight into the mechanisms of heme binding and
      transport. This review summarizes recent research on the Isd system with a focus
      on the structural biology of heme recognition.

PMID- 19853305
TI  - Influence of divalent copper, manganese and zinc ions on fibril nucleation and
      elongation of the amyloid-like yeast prion determinant Sup35p-NM.
AB  - There is a large body of evidence that divalent metal ions, particularly copper,
      might play a role in several protein folding pathologies like Alzheimer's
      disease, Parkinson's disease or the prion diseases. However, contribution of
      metal ions on pathogenesis and their molecular influence on the formation of
      amyloid structures is not clear. Therefore, the general influence of metals on
      the formation of amyloids is still controversially discussed. We have utilized
      the well established system of yeast Sup35p-NM to investigate the role of three
      different metal ions, Cu(2+), Mn(2+) and Zn(2+), on amyloidogenesis. Recently, it
      has been shown that the prion determining region NM of the Saccharomyces
      cerevisiae prion protein Sup35p, which is responsible for the yeast prion
      phenotype [PSI(+)], specifically binds Cu(2+) ions. We further characterized the
      affinity of NM for Cu(2+), which were found to be comparable to that of other
      amyloidogenic proteins like the mammalian prion protein PrP. The specific binding
      sites could be located in the aminoterminal N-region which is known to initiate
      formation of amyloidogenic nuclei. In the presence of Cu(2+), fibril nucleation
      was significantly delayed, probably due to influences of copper on the oligomeric
      ensemble of soluble Sup35p-NM, since Cu(2+) altered the tertiary structure of
      soluble Sup35p-NM, while no influences on fibril elongation could be detected.
      The secondary structure of soluble or fibrous protein and the morphology of the
      fibrils were apparently not altered when assembled in presence of Cu(2+). In
      contrast, Mn(2+) and Zn(2+) did not bind to Sup35p-NM and did not exhibit
      significant effects on the formation of NM amyloid fibrils.

PMID- 19853307
TI  - The sperm proteasome during sperm capacitation and fertilization.
AB  - The 26S proteasome is a multi-subunit protease specifically targeting
      ubiquitinated proteins. A consensus has emerged from studies by multiple
      laboratories on the role of sperm-borne proteasomes in human, mouse, pig, bovine,
      ascidian and echinoderm fertilization. Major findings from the studies in various
      mammalian and non-mammalian fertilization systems are (1) proteasomes are present
      in the mammalian sperm acrosome and on the acrosomal surface; (2) ubiquitinated
      proteins are present on the mammalian, ascidian and echinoderm egg coat; (3)
      proteasomal proteolytic and ubiquitin-deconjugating (deubiquitinating) activities
      can be detected in viable, motile mammalian spermatozoa; (4) proteasomes remain
      associated with the sperm head following ZP-induced acrosomal exocytosis; (5)
      inhibition of ubiquitination and proteasomal proteolysis blocks fertilization in
      mammals, ascidians and echinoderms; (6) inhibition of proteasomal proteolysis
      alters the course of mammalian sperm capacitation and acrosomal exocytosis
      induced by sperm binding to the egg coat, zona pellucida (ZP); (7) depletion of
      the sperm surface-associated ATP blocks porcine and echinoderm fertilization,
      most likely by affecting the integrity of sperm proteasomes, of which several
      subunits are ATPases; (8) inhibition of proteasomal proteolysis blocks sperm-ZP
      penetration, but does not alter the rate of sperm-ZP binding in mammals, and (9)
      experimental modification of sperm-associated deubiquitinating activities shifts
      the balance of monospermic fertilization to polyspermic fertilization in vitro.
      Altogether, these studies provide evidence for the involvement of the 26S
      proteasome in multiple steps of animal and human fertilization, offering a novel
      model of sperm-egg coat interactions, and identifying a range of potential new
      sperm quality markers and contraceptive targets.

PMID- 19853308
TI  - Modulation of innate immunity by IL-18.
AB  - IL-18 is expressed in various reproductive organs and its expression in the
      uterus fluctuates in linkage with menstrual cycle, implantation, pregnancy and
      delivery. However, the roles of this cytokine in reproduction remain obscure. IL
      18 is a pleiotropic cytokine and exerts apparently complicated and sometimes
      paradoxical functions in immune and inflammatory responses, and a consensus
      understanding of its action has not been attained. Recent investigations reveal
      that IL-18 activates anti-apoptotic signals and promotes both survival and
      proliferation of activated lymphocytes as well as various cells exposed to
      different stressors. Especially, IL-18 enhances the expansion of NK and
      gammadelta T cells isolated from the circulation and stimulated in various ways.
      The expansion of gammadelta T cells, stimulated by zoledronate and IL-2, was
      strongly promoted by exogenous IL-18 and was inhibited by neutralizing anti-IL-18
      receptor antibody. The expansion of gammadelta T cells was coincident with an
      increased number of CD11c+ cells. The gammadelta T cells that expanded in the
      presence of zoledronate, IL-2 and IL-18 exhibited the phenotype of effector
      memory cells characterized as CD44+ CD27- CD45RA- cells. In addition, they
      expressed NKG2D, perforin, CD94, CD25 and CD122, and 30-40% of them were positive
      for CD56. Incubation of expanded gammadelta T cells with IL-18 induced production
      of GM-CSF, IFNgamma and TNFalpha at much higher levels than those incubated
      without IL-18. They showed strong cytotoxicity against tumor cells, including
      mesothelioma cells, and inhibited growth of mesothelioma xenografts in mice.
      These observations suggest that IL-18 can efficiently promote expansion of
      gammadelta T cells with potent cytotoxicity.

PMID- 19853306
TI  - Pathways linking socioeconomic status to obesity through depression and lifestyle
      factors among young US adults.
AB  - Obesity and depression are two diseases of major public health importance. While
      both correlate with each other, potential pathways involving depression that
      would link socioeconomic status (SES) to lifestyle factors and obesity have not
      been systematically examined using nationally representative data. Using rich
      data on 2217 US young adults aged 20-39years from the 1999-2004 National Health
      and Nutrition Surveys (NHANES) and multivariate linear and logistic regression
      models, we examined associations between major depressive disorder (MDD), dietary
      intake, physical activity (PA), and measured body mass index (BMI) controlling
      for socio-demographic factors. Further, structural equation models (SEM) were fit
      to test pathway explaining SES disparities in BMI through MDD and lifestyle
      factors. Recent prevalence of MDD was lower among young US men than women (6.4%
      vs. 9.2%) although their prevalence of obesity was similar (21.2% vs. 22.7%).
      Among women, MDD was associated with higher BMI and inversely associated with PA,
      but not among men. MDD was specifically associated with increased risk of morbid
      obesity (BMI>/=40) among women (OR: 2.88 (1.32, 6.30)). Using SEM, a main pathway
      linking SES to BMI among women was linking SES-->food insecurity-->MDD-->PA-
      >BMI. A main pathway linking MDD to BMI in both genders was going through PA
      rather than overall dietary quality. Gender and ethnic differences existed
      underlying how MDD, SES and lifestyle factors were associated with adiposity.
      Future prospective studies are needed to examine potential mechanisms using
      physiological markers of depression, lifestyle and obesity.

PMID- 19853309
TI  - Molecular cloning, promoter analysis and SNP identification of Italian Nicastrese
      and Saanen lactoferrin gene.
AB  - Lactoferrin (Lf) is an iron-binding glycoprotein found in exocrine secretions
      including milk. High levels of lactoferrin may have a role in the prevention of
      microbial infection of the mammary gland. In this report we sequenced and
      characterized goat lactoferrin cDNA and its promoter region in two different
      breeds of goat. The complete cDNA comprised 2356 nucleotides, including 38 bp at
      the 5'-UTR and 194 bp at the 3'-UTR. The open reading frame is 2127 bp long and
      it encodes a mature protein of 689 aminoacids. A total of 19 nucleotide
      differences, 11 of them being responsible for 8 aminoacid changes, were
      identified through the comparison with French, Korean and Tibetan goat
      lactoferrin cDNAs. About 1700 bp of the lactoferrin gene promoter were sequenced.
      Sequence analysis revealed a non-canonical TATA box, multiple SP1/GC elements,
      and other putative binding sites for transcription factors, such as NF-kappaB,
      STAT3 and AP2. Two SNPs were identified, one of which would seem to create a new
      putative AP2 consensus sequence. The presence of an additional AP2 binding site
      could be associated with quantitative differences of such protein fraction, which
      could enhance all the activities related to such protein, and improve mammary
      gland defence against bacterial infections.

PMID- 19853310
TI  - Depressive emotioning in adolescents with cochlear implant and normal hearing.
AB  - OBJECTIVE: The purpose of this study is to compare the levels of depressive
      emotioning of adolescents with cochlear implants and the ones who have normal
      hearing. METHODS: For this purpose, Rosenberg Self-Esteem Scale is applied upon
      the study group which consists of 30 adolescents with cochlear implant between
      the ages of 12-19 and upon the control group which consists of 60 adolescents
      having the similar characteristics. The scale is used to evaluate the level of
      depressive emotioning of adolescents with cochlear implant and with normal
      hearing. RESULTS: At the end of the application, the scores of these two groups
      which they got according to their answers were compared statistically. When the
      results were examined, there seemed to be no significant difference statistically
      between the depressive emotioning values of the cochlear implant group and the
      control group. Apart from this, in this study, we examined changes in the level
      of depressive emotioning according to different variables. As a result, it was
      found out that in both groups level of depressive emotioning was lower for
      adolescents who had had preschool education, had brothers/sisters, high level of
      income, whose father and mother had higher levels of education. On the other
      hand, the birth sequence and the child's father's profession did not seem to have
      any effect on the child's level of depressive emotioning. CONCLUSIONS: As a
      result of these findings, it was thought that cochlear implantation had a
      positive effect on life quality and it was suggested that the adolescents and
      their families should get assistance from experts about the characteristics and
      principles of approaching the child in this period. The adolescent should be
      directed towards social activities and courses, their positive sides should be
      supported and further studies should be carried out with different case groups on
      this matter. In addition to, examining the interactions of hearing loss effects
      can help professionals determine the individuals who are at a higher risk for
      developing mental distress.

PMID- 19853311
TI  - Evaluation for language and speech development in Kabuki make-up syndrome: a case
      report.
AB  - Kabuki make-up syndrome (KMS) is defined as a rare syndrome with mental
      retardation, growth deficiency and multiple anomalies of unknown cause. Cases
      have a characteristic facial appearance of broad and low auricles, wide forehead,
      broad and flattened nose root. In this article, 4-year, 10-month-old boy with
      speech delay reported due to characteristics of the facial appearance is
      considered as KMS, a rare syndrome. Otological, audiological and developmental
      evaluation of the patient consisted of six parameters. (1) ENT examination:
      normal. (2) Audiological findings were at normal hearing levels. (3) General
      development (according to the Denver II test), was normal. (4) Language and
      speech development: receptive language development was 2 years more than the
      chronological age. However in expressive language development, there was 5-month
      delay which was likely to complete by training in a short time. (5) The
      development of speech sounds and articulation: the delay is observed in CVC
      words. Speech sounds of /l/, /t/, /r/ and /g/ were evaluated as "distorted
      expression". He used /v/ instead of /l/; /y/ instead of /r/; /d/ instead of /g/.
      (6) OBSERVATIONS: diffident, deficit in self-confidence, and difficulty in
      communicating have been observed.Unlike the cases in literature, mental
      retardation, growth deficiency and learning difficulties were not found in our
      case with KMS. Normal findings were obtained in five parameters. Only the /l/,
      /r/ and /g/ speech sounds were expressed as distorted. For our case, we planned
      to follow him in the future to see whether developmental and central auditory
      processing disorders will occur or not.

PMID- 19853312
TI  - Effect of lipooligosaccharide mutations of Haemophilus influenzae on the middle
      and inner ears.
AB  - OBJECTIVE: The purpose of this study was to determine the virulence of
      nontypeable Haemophilus influenzae 2019 (NTHi 2019) and its two
      lipooligosaccharide (LOS) mutant strains, B29 (gene htrB) and DK1 (gene rfaD),
      and compare their effect on the middle ear, round window membrane, and inner ear.
      RESULTS: Fifteen chinchillas were divided into three equal groups and their
      bullas inoculated bilaterally with 0.5 ml of 10(2)CFU/ml of parent NTHi 2019, B29
      or DK1 mutant strains. Two days after inoculation all animals had otitis media
      and inflamed middle ear mucosa. There was a trend of greater thickness and
      infiltration of the round window membrane in animals inoculated with the wild
      type NTHi strain compared to the mutant strains and a significant increase in
      both inflammatory cell infiltration and bacteria presence in the scala tympani
      area of the inner ear. Strial edema was only observed in the wild-type-inoculated
      group. CONCLUSIONS: LOS mutants of NTHi appear to have a reduced ability to pass
      through the round window membrane resulting in less inner ear inflammation and
      pathological changes.

PMID- 19853313
TI  - Needs of caregivers of the patients with dementia.
AB  - This study was conducted to isolate the needs families express both for medical
      and psychological care, and for educational and social support in 112 caregivers
      of patients affected by moderate to severe dementia (mini mental state
      examination=MMSE score: 9+/-7) consecutively recruited at our Memory Clinic, to
      develop approaches as individualized as possible. The medical needs caregivers
      express are mainly relative to a better knowledge of the disease (78%) and the
      exact diagnosis (65%); the education-related needs are mainly relative to the
      acquisition of communicational skills (83%) and the optimal handling of cognitive
      (77%) and behavioral disorders (81%); the psychological ones mainly concern the
      area of assistance induced emotional stress management (37%) and the elaboration
      of feelings such as anxiety, rage and guilt (49%). Variance analysis shows a
      correlation between emotional caregivers' needs and the subjective and objective
      burdens they carry. Despite the attention to the role families play in caring for
      patients with a diagnoses of moderate to severe dementia, caregivers still
      express low levels of illness-consciousness and high levels of psychological
      discomfort. A lot more ought to be done in order to provide better information
      about the disease, about appropriate cognitive and behavioral disorder management
      skills, and about viable psychological support.

PMID- 19853314
TI  - High levels of mannose-binding lectin are associated with the risk of severe
      cardiomyopathy in chronic Chagas Disease.

PMID- 19853315
TI  - A study of middle ear function in the treatment of nasopharyngeal carcinoma with
      IMRT technique.
AB  - PURPOSE: This study evaluates the difference in damage to middle ear function
      with CRT and IMRT techniques in the treatment of nasopharyngeal carcinoma (NPC).
      We explore the isthmus of the Eustachian tube (ET) as the key anatomic site for
      the prevention of radiation-induced otitis media with effusion. METHODS AND
      MATERIALS: Eighty-two patients with NPC were divided into two groups: 40 patients
      treated with CRT and 42 patients treated with IMRT. The difference between dosage
      over the middle ear cavity and the isthmus of the ET was evaluated in both CRT
      group and IMRT group. All patients underwent hearing tests including pure tone
      audiometry and impedance audiometry before and after RT. RESULTS: The dosage
      difference to the middle ear cavity and isthmus between these two groups was
      statistically significant (p<0.05). The difference in hearing test results
      between these two groups was also statistically significant (p<0.05). If we
      limited the dose to the middle ear cavity under 34 Gy and the dose to the isthmus
      under 53 Gy with IMRT, we may decrease radiation-induced OME even with the larger
      2.25 Gy fraction size. CONCLUSIONS: IMRT may have better protected the middle ear
      function compared with the CRT technique, even with larger fraction sizes than
      for the conventional CRT technique.

PMID- 19853316
TI  - Delineation guidelines for organs at risk involved in radiation-induced salivary
      dysfunction and xerostomia.
AB  - BACKGROUND AND PURPOSE: It is believed that minimizing inconsistencies in OAR
      volume definition will help to improve adequate reporting and interpreting of
      radiation treatment results. The aim of this paper is to introduce computed
      tomography (CT)-based delineation guidelines for organs at risk (OARs) in the
      head and neck area, associated with radiation-induced salivary dysfunction and
      xerostomia. MATERIAL AND METHODS: After analyses of the human anatomy of the head
      and neck area, computed tomography (CT)-based guidelines for delineation of the
      most relevant OARs were described by a panel of experts. RESULTS AND CONCLUSIONS:
      The provided OAR guidelines are accompanied by CT-based illustrations presenting
      examples of the delineated structures and their corresponding anatomic
      boundaries. The parts of the tongue bearing minor salivary glands could not be
      outlined. Difficulties and uncertainties in defining these minor salivary glands
      on CT remain to be resolved. Implementation of these guidelines in practice
      should lead to a reduction in inter- and intra-observer variability and therefore
      unambiguous reporting of possible dose-volume effect relationships.

PMID- 19853317
TI  - Re: Accelerated partial breast irradiation as part of breast conserving therapy
      of early breast carcinoma: a systematic review.

PMID- 19853318
TI  - Amount and structure of force variability during short, ramp and sustained
      contractions in males and females.
AB  - The aim of this study was to investigate the effect of gender differences on
      force variability as assessed by means of linear and nonlinear estimators during
      short duration, ramp and sustained isometric elbow flexions. Ten males and ten
      females performed elbow flexion receiving visual feedback from the direction of
      force exertion. Isometric elbow flexions were performed during: maximum voluntary
      contraction (MVC before and after endurance test), short contraction at 10-90%
      MVC with 10% increment for 5s, ramp contraction from 5% to 50% MVC over 30s, and
      endurance contraction at 20% MVC. Standard deviation (SD), coefficient of
      variations (CV), and sample entropy (SaEn) were computed from the force signals
      recorded in 3D. During short and ramp contraction, SD increased with contraction
      level while SaEn followed an inverted U-shape function (p<.01). During endurance
      test, SD and CV increased with contraction time (p<.01). SD and SaEn were
      consistently higher in males than females while it was opposite for CV (p<.05).
      Separate control and compensatory mechanisms could be responsible for the
      observed changes in the amount and structure of task-related and tangential
      forces variability. Moreover, gender differences most likely point towards gender
      dependent force control mechanisms. The lower magnitude and structure of
      variability observed in females may increase the risk of muscle overload and
      damage.

PMID- 19853319
TI  - Crossborder trade in health services: Lessons from the European laboratory.
AB  - We find four key lessons that health policymakers and practitioners should be
      aware of: the potential of services liberalization to incur high transition and
      transaction costs; the difficulty of reconciling economic and social policy goals
      and the subsequent high likelihood of backlash; the tendency of rule-based
      systems to promote policy spillover; and the importance (and difficulty) of early
      monitoring in order to avoid unwanted policy outcomes. We conclude that continued
      awareness of new policy developments, coordination of expertise on health and
      trade and preemptive regulation are vital in order to deal with the expansion of
      crossborder trade in health services.

PMID- 19853320
TI  - The demand for preventive care services and its relationship with inpatient
      services.
AB  - OBJECTIVE: To examine not only the relationship between the utilization of
      preventive health care services and inpatient services, but to also investigate
      the factors affecting the utilization of such services by the middle-aged and
      elderly. METHOD: We use data obtained from the 2003 Survey of Health and Living
      Status of the Elderly in Taiwan (SHLSE), hypothesizing that preventive health
      care services can be regarded as an appropriate substitute for subsequent medical
      services such as inpatient services; a recursive simultaneous model is used to
      avoid the problems of endogeneity. RESULTS: The main results of this study
      indicate that the utilization of preventive health care services has the effect
      of reducing the probability of the utilization of inpatient services. CONCLUSION:
      The utilization of preventive care services can help to promote healthier
      lifestyles, provide early detection of illnesses, and reduce the need for
      subsequent inpatient care services amongst individuals. We suggest that effective
      outreach strategies to promote the utilization of preventive care services are
      essential.

PMID- 19853321
TI  - Towards an evolutionary ecology of sexual traits.
AB  - Empirical studies of sexual traits continue to generate conflicting results,
      leading to a growing awareness that the current understanding of this topic is
      limited. Here we argue that this is because studies of sexual traits fail to
      encompass three important features of evolution. First, sexual traits evolve via
      natural selection of which sexual selection is just one part. Second, selection
      on sexual traits fluctuates in strength, direction and form due to spatial and
      temporal environmental heterogeneity. Third, phenotypic plasticity is ubiquitous
      and generates selection and responses to selection within and across generations.
      A move from purely gene-focused theories of sexual selection towards research
      that explicitly integrates development, ecology and evolution is necessary to
      break the stasis in research on sexual traits.

PMID- 19853322
TI  - [Falls: geriatric syndrome par excellence].

PMID- 19853323
TI  - [Changes in the incidence of falls in an intermediate and long-term care center].
AB  - INTRODUCTION: The characteristics of falls in older patients admitted to an
      institution in 2 different periods. MATERIAL AND METHODS: We performed a
      prospective study of falls among inpatients admitted to an intermediate and long
      term care center. Age, sex, Barthel index, main diagnoses, medication at the time
      of the fall, place, the shift when the fall occurred, lighting, characteristics
      of the floor, the use of walking aids and/or restraints, the kind of shoes worn,
      and activity at the moment of the fall were registered. During the first 2-year
      study period (period A), there were 332 beds (intermediate care and
      rehabilitation unit, long-term care unit, palliative care unit, psychogeriatric
      unit and assisted residential home). During the second 2-year period (period B),
      the palliative and intermediate care units were moved to another center (255 beds
      remaining). RESULTS: Period A: there were 647 falls in 227 patients; the total
      number of patients admitted was 1387 (accumulated incidence of falls: 46.6%).
      Period B: there were 539 falls in 191 patients; the total number of patients
      admitted was 908 (accumulated incidence of falls: 59.3%). Significant differences
      between the two periods were found in age (79.8+/-10.6 versus 81.3 10.2)
      (p<0.02), the percentage of women (55.2% versus 66.4%) (p<0.001), neurological
      diagnoses (26.7% versus 36.1%) (p< 0.001), antidepressants (12.6% versus 16.4%),
      neuroleptics (10.3% versus 15.2%) (p<0.001), falls in the bedroom (39.7% versus
      41.6%) (p<0.001), falls when moving from bed to chair (41.3% versus 30.8%)
      (p<0.001), and the use of walking aids (65.8% versus 40.5%) (p<0.001).
      CONCLUSIONS: a) the incidence of falls increased in the second period of the
      study; b) in period A, risk factors for falls related to rehabilitation (moving
      from bed to chair, use of walking aids) were more frequent. In period B, risk
      factors related to the characteristics of psychogeriatric patients were
      predominant (neurological illness, use of psychotropic drugs, and c) the
      difference in the incidence of falls between the two study periods may be related
      to the distinct characteristics of the patients (case mix).

PMID- 19853324
TI  - [Inguinal herniation of a bladder diverticulum, diagnosed by PET-CT].

PMID- 19853325
TI  - [Utility of bone SPECT-CT in percutaneous vertebroplasty].
AB  - Percutaneous vertebroplasty is a minimally invasive procedure that has shown
      excellent results in the treatment of back pain due to acute-subacute vertebral
      fracture. The bone scintigraphy shows the increase of metabolic exchange in the
      fracture. The new hybrid SPECT-CT equipment combines bone SPECT images with
      Computed Tomography (CT), making it possible to obtain more combined, functional
      and anatomical information. We present 5 selected patients studied by bone SPECT
      CT in whom fused images made it possible to obtain a more precise localization of
      the pain origin, and thus assess other possible causes of the vertebral pain or
      even reassess the vertebroplasty indication.

PMID- 19853327
TI  - Synthesis of some new pyrazolo[3,4-d]pyrimidine derivatives of expected
      anticancer and radioprotective activity.
AB  - On the account of the reported anticancer activity of pyrazolo[3,4-d]pyrimidines,
      a new series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized and tested
      for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell
      line. Moreover, one of the target products was evaluated for in-vivo
      radioprotective activity. The reaction of o-aminoester 1 with benzylamine in
      presence of triethylorthoformate yielded the corresponding 5
      benzylpyrazolopyrimidine derivative 2. The N-amino derivative 3 was used to
      synthesize new derivatives of pyrazolopyrimidines 4-7. The corresponding 1,3,4
      oxadiazolopyrazolopyrimidine derivatives 12 and 14 were obtained via reaction of
      compound 9 with reagent 10 and/or triethylorthoformate. Thiophosgenation of
      compound 1 furnished the corresponding 5-isothiocyanate derivative 15, which was
      reacted with o-phenylenediamine, thiosemicarbazide and anthranilic acid to give
      benzimidazolopyrazolopyrimidine, 17, pyrazolotriazolopyrimidine, 19 and
      pyrazolopyrimidobenzoxazine, 20 respectively. The structures of the synthesized
      compounds were confirmed by microanalyses, IR, NMR, and mass spectral data.
      Compounds 2 and 9 showed intermediate anticancer activity compared to doxorubicin
      as positive control with IC50 values of 90 and 100 microg/ml, respectively. On
      the other hand, compound 5 showed significant radioprotective effect.

PMID- 19853326
TI  - [Three outbreaks of brucellosis in a one-year period investigated by the
      occupational health service in Ciudad Real (Spain)].
AB  - We describe 3 outbreaks of brucellosis investigated by our Occupational Health
      Service in a 1-year period. Two of these outbreaks, with 2 cases each, occurred
      in 2 cheese factories and the third outbreak, also with 2 cases, occurred in a
      cattle laboratory belonging to the local government. In both cheese factories,
      numerous opportunities for the workers to become infected were found. The
      greatest risk was considered to be the area for unloading milk, while failure to
      use personal protection equipment by workers, deficiencies in the laboratories,
      and the lack of effective separation between areas were also potential risk
      factors. In the cattle laboratory, we found at least 13 major risk factors that
      could allow brucellosis transmission. In Spain, there is a substantial risk of
      Brucella infection in laboratories or dairy factories and current preventive
      measures are ineffective.

PMID- 19853329
TI  - 1,3-Dipolar cycloaddition of C-aryl-N-phenylnitrones to (R)-1-(1-phenylethyl)-3
      [(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: synthesis and
      antimycobacterial evaluation of enantiomerically pure spiroisoxazolidines.
AB  - A series of novel enantiomerically pure spiroisoxazolidines were synthesized
      regioselectively by the 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones to
      (R)-1-(1-phenylethyl)-3-[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones. These
      compounds have been screened for their in vitro activity against Mycobacterium
      tuberculosis H37Rv (MTB) using agar dilution method. Among the twenty two
      compounds screened, (3S,4S,5R)-3,4-di(4-methylphenyl)-2-phenyl-7-[(R)-1
      phenylethyl]-1-oxa-2,7-diazaspiro[4.5]decan-10-one (3e) was found to possess the
      maximum activity with MIC of 3.02 microM, being 2.5 times more potent than the
      first-line anti-TB drug ethambutol. For comparison, a series of ten
      enantiomerically pure spirooxazolines were also screened, among which (4R,5S)-3,4
      bis(4-chlorophenyl)-7-[(R)-1-phenylethyl]-1-oxa-2,7-diazaspiro[4.5]dec-2-en-10
      one and (4R,5S)-4-(2-chlorophenyl)-3-(4-chlorophenyl)-7-[(R)-1-phenylethyl]-1-oxa
      2,7-diazaspiro[4.5]dec-2-en-10-one were found to display maximum activity with
      MIC of 3.25 microM.

PMID- 19853328
TI  - Synthesis, spectral characterization and biological evaluation of phosphorylated
      derivatives of galanthamine.
AB  - A series of novel phosphorylated derivatives of galanthamine 6-11 and 12-17 were
      synthesized in two step process with high yields. In the first step galanthamine
      1 was reacted with bis (2-chloroethyl) phosphoramidic dichloride 2/4-nitrophenyl
      phosphorodichloridate 3 in presence of triethylamine (TEA) in dry tetrahydrofuran
      (THF) yielded the intermediates 4/5. They were further reacted with various
      compounds like 2-aminoethanol, ethyleneglycol, ethylenediamine, 2
      aminoethanethiol, 2-hydroxyethanethiol, monopotassium dihydrogenphosphate to
      obtain the title compounds 6-11 and 12-17. The title compounds showed promising
      antimicrobial, antioxidant activities and was greatly influenced by the presence
      of different bioactive groups.

PMID- 19853330
TI  - [Behcet's disease diagnosis].

PMID- 19853331
TI  - [Multiresistant tuberculosis].

PMID- 19853333
TI  - Factors affecting the success of moxibustion in the management of a breech
      presentation as a preliminary treatment to external cephalic version.
AB  - OBJECTIVES: to explore the effects of moxibustion treatment, to examine the
      predictors of its use in causing a breech presentation to spontaneously turn to a
      cephalic presentation which will result in a vaginal birth (the paper will refer
      to this as 'successful') and offer external cephalic version (ECV) subsequently
      after moxibustion treatment when the fetus remains in a breech presentation.
      DESIGN: a prospective study over a two-year time period from February 2004 until
      January 2006. PARTICIPANTS: 76 pregnant women from various acupuncture practices
      in the UK, with a third trimester breech presentation. INTERVENTIONS: the
      acupuncturist taught the women how to apply moxibustion (sticks of compressed
      dried herbs-Artemisia vulgaris) treatment at home by stimulating the acupoint on
      the outer edge at the base of the little toe nail for seven days twice a day
      (morning and afternoon). If the breech presentation persisted after treatment,
      ECV was carried out towards the end of the pregnancy. The obstetricians offered
      this during the routine antenatal hospital visits. FINDINGS: the results show
      that following treatment with moxibustion, 31 (40.8%) of the breech presentations
      spontaneously turned to cephalic presentations, and a further 33 (43.4%) breech
      presentations were turned by ECV. Women who involved other people in the
      administration of moxibustion were twice as likely to be successful. Multiparous
      women were also 16% more likely than primiparous women to succeed in achieving a
      spontaneous version with the use of moxibustion. Fewer side effects reported when
      using moxibustion were the strongest predictor of successful spontaneous cephalic
      version with an odds ratio of 12% (p = 0.02). KEY CONCLUSIONS: moxibustion
      creates a better chance of vaginal birth for expectant mothers. Of the women who
      were successful in turning their babies using moxibustion, 88% went on to have a
      normal birth and 12% had a caesarean section. Moxibustion treatment also
      significantly increases version from a breech presentation to a cephalic
      presentation where there are fewer side effects reported, if the woman is
      multiparous and has support during the administration of moxibustion treatment.
      IMPLICATIONS FOR PRACTICE: moxibustion treatment should be offered to all women
      with a breech presentation because it is non-invasive and can be self
      administered by the woman. It is therefore a simple, cost-effective technique
      that requires no medical intervention.

PMID- 19853332
TI  - The S-100B substudy of the GLUTAMICS trial: glutamate infusion not associated
      with sustained elevation of plasma S-100B after coronary surgery.
AB  - BACKGROUND & AIMS: Concerns have been raised about potential neurological injury
      related to exogenous glutamate. In cardiac surgery glutamate has been
      administered as a putative cardioprotective agent by cardioplegia or intravenous
      infusion. In the GLUTAMICS trial, in addition to surveillance of clinical
      neurological injuries, a prespecified subgroup was analyzed with regard to
      postoperative S-100B levels to detect potential subclinical neurological injury
      related to glutamate infusion. METHODS: Sixty-nine patients operated on for
      unstable coronary syndrome were randomized to intravenous infusion of glutamate
      (n=35) or saline (n=34) perioperatively. Plasma levels of S-100B were obtained on
      the third postoperative day. RESULTS: S-100B in the glutamate group and the
      control group were 0.079+/-0.034microg/L and 0.090+/-0.042microg/L respectively
      (p=0.245). There were no patients with stroke or mortality. Three patients in the
      control group and two in the glutamate group had postoperative confusion. These
      patients had significantly elevated S-100B compared with those without confusion
      (0.132+/-0.047vs 0.081+/-0.036microg/L; p=0.003). Overall, 21 patients had S-100B
      above reference level (> or =0.10microg/L) and these patients had significantly
      more calcifications in the ascending aorta on epiaortic scanning. CONCLUSIONS:
      Intravenous glutamate infusion during surgery for unstable coronary artery
      disease did not initiate a sustained elevation of plasma S-100B. Thus, no
      evidence for subclinical neurological injury related to glutamate infusion was
      found. In contrast, postoperative elevation of plasma S-100B was linked to
      calcification of the ascending aorta and postoperative confusion.

PMID- 19853334
TI  - In vivo deep-flexion kinematics in patients with posterior-cruciate retaining and
      anterior-cruciate substituting total knee arthroplasty.
AB  - BACKGROUND: Posterior-cruciate ligament retaining total knee arthroplasty designs
      have long been used with excellent clinical success, but often have shown
      kinematics and flexion performance that are significantly different from the
      natural knee. The purpose of this study was to compare deep-flexion knee
      kinematics in patients with two types of posterior-cruciate ligament retaining
      total knee arthroplasty. METHODS: One group received a traditional curved
      symmetric articular configuration, and one group received a design incorporating
      a lateral compartment which constrains the lateral condyle to the antero
      posterior center of the tibial plateau in extension, but allows translation in
      flexion--roughly approximating the role of the anterior cruciate ligament. In
      vivo kinematics were analyzed using three-dimensional model registration and
      plain radiographs of kneeling and squatting activities in 20 knees in 18
      patients. FINDINGS: Knees with the anterior cruciate ligament substituting design
      exhibited greater flexion, femoral antero-posterior translation and tibial
      internal rotation. INTERPRETATION: Geometric features intended to improve knee
      flexion, including greater antero-posterior stability, a more posterior tibial
      sulcus, and reshaped femoral condyles, do provide measurable and significant
      differences in deep-flexion knee kinematics.

PMID- 19853335
TI  - Risk factors for CKD in persons with kidney stones: a case-control study in
      Olmsted County, Minnesota.
AB  - BACKGROUND: Kidney stones are associated with increased risk of chronic kidney
      disease (CKD); however, risk factors in the general community are poorly defined.
      STUDY DESIGN: A nested case-control study was performed in residents of Olmsted
      County, MN, who presented with a kidney stone at the Mayo Clinic in 1980-1994 to
      contrast patients with kidney stones who developed CKD with a group that did not.
      SETTING & PARTICIPANTS: Participants were selected from the Rochester
      Epidemiology Project, an electronic linkage system among health care providers in
      Olmsted County, MN. Cases were identified by diagnostic code for CKD and
      confirmed to have an estimated glomerular filtration rate < 60 mL/min/1.73 m(2).
      Controls were matched 2:1 to cases for age, sex, date of first kidney stone, and
      length of medical record. PREDICTOR: Charts were abstracted to characterize stone
      disease, hypertension, diabetes, obesity, tobacco use, ileal conduit, symptomatic
      stones, type and number of stones, urinary tract infections, number and type of
      surgical procedures, and medical therapy. OUTCOMES & MEASUREMENTS: Kidney stone
      patients with CKD were compared with matched stone patients without CKD. RESULTS:
      There were 53 cases and 106 controls with a mean age of 57 years at first stone
      event and 59% men. In kidney stone patients, cases with CKD were significantly
      more likely (P < 0.05) than controls to have had a history of diabetes (41.5% vs
      17.0%), hypertension (71.7% vs 49.1%), frequent urinary tract infections (22.6%
      vs 6.6%), struvite stones (7.5% vs 0%), and allopurinol use (32.1% vs 4.7%) based
      on univariate analysis. LIMITATIONS: Potential limitations include limited
      statistical power to detect associations, incomplete data from 24-hour urine
      studies, and that stone composition was not always available. CONCLUSION: As in
      the general population, hypertension and diabetes are associated with increased
      risk of CKD in patients with kidney stones. However, other unique predictors were
      identified in patients with kidney stones that increased the possibility of CKD.
      Further studies are warranted to elucidate the nature of these associations.

PMID- 19853336
TI  - Association of hemodialysis treatment time and dose with mortality and the role
      of race and sex.
AB  - BACKGROUND: The association of survival with characteristics of thrice-weekly
      hemodialysis (HD) treatment, including dose or duration of treatment, has not
      been completely elucidated, especially in different race and sex categories.
      STUDY DESIGN: We examined associations of time-averaged and quarterly varying
      (time-dependent) delivered HD dose and treatment time and 5-year (July 2001-June
      2006) survival. SETTING & PARTICIPANTS: 88,153 thrice-weekly-treated HD patients
      from DaVita dialysis clinics. PREDICTORS: HD treatment dose (single-pool Kt/V)
      and treatment time. OUTCOMES & OTHER MEASUREMENTS: 5-Year mortality. RESULTS:
      Thrice-weekly treatment time < 3 hours (but > or = 2.5 hours) per HD session
      compared with > or = 3.5 hours (but < 5 hours) was associated with increased
      death risk independent of Kt/V dose. The greatest survival gain of higher HD dose
      was associated with a Kt/V approaching the 1.6-1.8 range, beyond which survival
      gain was minimal, nonexistent, or even tended to reverse in African American men
      and those with 4-5 hours of HD treatment. In non-Hispanic white women, Kt/V > 1.8
      continued to show survival advantage trends, especially in time-dependent models.
      LIMITATIONS: Our results may incorporate uncontrolled confounding. Achieved Kt/V
      may have different associations than targeted Kt/V. CONCLUSIONS: HD treatment
      dose and time appear to have different associations with survival in different
      sex or race groups. Randomized controlled trials may be warranted to examine
      these associations across different racial and demographic groups.

PMID- 19853338
TI  - The contribution of new social science research to patient safety.
AB  - Social sciences have given much to the science and practice of patient safety,
      but have more to offer. The purposes of this paper are to give a background to
      the studies presented in this special issue, and to encourage more social
      scientist to contribute to this important and rapidly growing field. This is
      largely preaching to the converted - there is one other purpose which may be
      achieved if more traditional medical researchers and reviewers see this special
      issue. That is to show how social sciences help to understand, explain and
      address many issues which traditional medical research methods are not designed
      to penetrate. This special issue shows the value of social science patient safety
      research, and gives a reference point for future researchers in making proposals,
      designing research and comparing their findings. It highlights areas which this
      research needs to address in its methods, presentation, and subjects studied.

PMID- 19853337
TI  - Intradialytic hypertension: a less-recognized cardiovascular complication of
      hemodialysis.
AB  - Intradialytic hypertension, defined as an increase in blood pressure during or
      immediately after hemodialysis that results in postdialysis hypertension, has
      long been recognized to complicate the hemodialysis procedure, yet often is
      largely ignored. In light of recent investigations suggesting that intradialytic
      hypertension is associated with adverse outcomes, this review broadly covers the
      epidemiologic characteristics, prognostic significance, potential pathogenic
      mechanisms, prevention, and possible treatment of intradialytic hypertension.
      Intradialytic hypertension affects up to 15% of hemodialysis patients and occurs
      more frequently in patients who are older, have lower dry weights, are prescribed
      more antihypertensive medications, and have lower serum creatinine levels. Recent
      studies associated intradialytic hypertension independently with higher
      hospitalization rates and decreased survival. Although the pathophysiologic
      mechanisms of intradialytic hypertension are uncertain, it likely is
      multifactorial and includes subclinical volume overload, sympathetic
      overactivity, activation of the renin-angiotensin system, endothelial cell
      dysfunction, and specific dialytic techniques. Prevention and treatment of
      intradialytic hypertension may include careful attention to dry weight, avoidance
      of dialyzable antihypertensive medications, limiting the use of high-calcium
      dialysate, achieving adequate sodium solute removal during hemodialysis, and
      using medications that inhibit the renin-angiotensin-aldosterone system or
      decrease endothelin 1 levels. In summary, although intradialytic hypertension
      often is underappreciated, recent studies suggest that it should not be ignored.
      However, further work is necessary to elucidate the pathophysiologic mechanisms
      of intradialytic hypertension and its appropriate management and determine
      whether treatment of intradialytic hypertension can improve clinical outcomes.

PMID- 19853339
TI  - Routine checks for HIV in children attending primary health care facilities in
      South Africa: attitudes of nurses and child caregivers.
AB  - Management of HIV-infected and exposed children is challenging for health workers
      in primary care settings. Integrated management of childhood illness (IMCI) is a
      WHO/UNICEF strategy for improving morbidity and mortality in under 5 children
      attending first level facilities in developing countries. In high HIV-prevalence
      settings, IMCI includes an HIV component for identification and management of HIV
      infected and exposed children, which requires health workers to ask all mothers
      about their HIV status and check all children for signs of HIV. Effective
      implementation of the HIV component depends on the ability and willingness of
      health workers to take every opportunity to identify HIV-infected children during
      routine care, and implementation in South Africa is poor. In 2006, we conducted
      10 focus groups in two provinces in South Africa with IMCI-trained nurses, and
      with mothers attending first level facilities, to determine their attitudes
      towards, and experiences of, routine checks for HIV during consultations with
      sick children. Nurses were frequently unwilling to check for HIV in all children,
      believing it was unnecessary, unacceptable to mothers, and that they lack skills
      to implement HIV care. Nurses feared mothers would become upset or make a
      complaint. Mothers consistently recognised the importance of checking children
      for HIV and supported implementation of routine checks, although the attitude of
      the nurse was important in determining the acceptability of HIV-related
      questions. Mothers expressed fears about lack of confidentiality from nurses, and
      that receiving HIV-related services could lead to unintentional disclosure of
      their HIV status. Nurses lack the skills in HIV management and communication
      skills to implement the HIV component of IMCI. We identify issues relate to
      improved training, clear policies on record keeping, and organization of health
      services to respect privacy and confidentiality, to improve the willingness of
      health workers to provide HIV care and mothers to accept it.

PMID- 19853340
TI  - Social scientists and patient safety: critics or contributors?
AB  - Patient safety has been high on the national and international agenda in
      healthcare for almost a decade. It is proving to be a tough problem; tough in
      cultural, technical, clinical, and psychological terms and because of its massive
      scale and heterogeneity. While many of the challenges and problems of patient
      safety are social and organisational, few social scientists are involved in
      patient safety. Clinicians and clinical researchers are for the most part open to
      other perspectives, but that they may not fully appreciate the potential
      contribution of the social sciences. Social scientists can, for instance, assist
      in drawing attention to the need to take an account of the social and cultural
      context of patient safety interventions, by drawing on narratives and stories to
      illuminate organisational processes and by encouraging greater use of
      ethnographic and observational research. However, if social scientists are to
      have a real impact they need to do more than simply offer critiques of patient
      safety and move to active engagement with clinicians and patient safety
      researchers.

PMID- 19853341
TI  - "Broad" consent, exceptions to consent and the question of using biological
      samples for research purposes different from the initial collection purpose.
AB  - An important ethical issue regarding biological samples stored in biobanks is
      unforeseen future sample use, when no or limited subject consent is obtained.
      Biobanks of biological samples have significant future research potential, but
      may cause conflicts of interest regarding the consent obtained. Indeed, ethics,
      deontology, and jurisprudence generally advise that consent must be specific and
      circumstantiated. However, it is not possible to foresee all of the future
      circumstances in which the samples might be useful, nor is it possible to re
      contact all subjects in order to gain consent for a new use. The main arguments
      for the use of "broad" consent are presented with a brief discussion of the
      conditions where it may be legitimate not to obtain consent. Particular attention
      is given to the expressed positions of national and international bioethics
      bodies.

PMID- 19853342
TI  - Promoting health equity in conflict-affected fragile states.
AB  - Issues around health equity in conflict-affected fragile states have received
      very little analysis to date. This paper examines the main factors that threaten
      health equity, the populations that are most vulnerable and potential strategies
      to improve health equity. The methods employed are a review of the published and
      grey literature, key informant interviews and an analysis of data on social
      determinants of health indicators. A new conceptual framework was developed
      outlining types of inequity, factors that influence equity and possible
      strategies to strengthen equity. Factors that affect equity include displacement,
      gender and financial barriers. Strategies to strengthen health equity include
      strengthening pro-equity policy and planning functions; building provider
      capacity to provide health services; and reducing access and participation
      barriers for excluded groups. In conclusion, conflict is a key social determinant
      of health. More data is needed to determine how conflict affects within-country
      and between-country equity, and better evaluated strategies are needed to reduce
      inequity.

PMID- 19853343
TI  - Managed care and measuring medical outcomes: did the rise of HMOs contribute to
      the fall in the autopsy rate?
AB  - The U.S. autopsy rate has fallen precipitously since the 1940s, decreasing from
      50 percent of bodies to less than eight percent today. Much of the decrease
      occurred after 1971 when hospitals were no longer required to do a minimum number
      of autopsies for accreditation. Since this time, major changes in the health care
      sector have occurred in the United States, highlighted by the increased
      importance of managed care. Using data for 46 states from 1987 to 2000, we
      analyze the degree to which the rise in manage care explains the decrease in the
      autopsy rate. We find that increases in health maintenance organization market
      share explain 21 percent of the decrease in the autopsy rate over the years from
      1987 to 2000 and reductions in the number of hospital deaths explain another 30
      percent. In contrast, we find that increases in the availability of magnetic
      resonance imaging had no significant effect on autopsy rates when other factors
      are held constant. Reforming health care financing to restrain the growth in
      health care costs using incentive mechanisms similar to those employed by managed
      care organizations has been a recurring policy goal in the United States. Our
      results imply that these reforms may inadvertently reduce the incentive to
      monitor medical outcomes using techniques such as autopsies, which is often
      called the "gold standard" in measuring medical outcomes.

PMID- 19853344
TI  - Uptake of a team briefing in the operating theatre: a Burkean dramatistic
      analysis.
AB  - Communication among healthcare professionals is a focus for research and policy
      interventions designed to improve patient safety, but the challenges of changing
      interprofessional communication patterns are rarely described. We present an
      analysis of 756 preoperative briefings conducted by general surgery teams
      (anesthesiologists, nurses, and surgeons) at four urban Canadian hospitals in the
      context of two research studies conducted between August 2004 and December 2007.
      We ask the questions: how and why did briefings succeed, how and why did they
      fail, and what did they mean for different participants? Ethnographic fieldnotes
      documenting the coordination and performance of team briefings were analyzed
      using Kenneth Burke's concepts of motive and attitude. The language and behaviour
      of participants were interpreted as purposive and situated actions which reveal
      perceptions, beliefs and values. Motives and attitudes varied both within and
      across sites, professions, individuals, and briefings. They were contingent on
      the organizational, medical and social scenes in which the briefings took place
      and on participants' multiple perceived purposes for participating (protecting
      patient safety, exchanging information, engaging with the team, fulfilling
      professional commitments, participating in research, and meeting social
      expectations). Participants' attitudes reflected their recognition (or rejection)
      of specific purposes, the briefings' perceived effectiveness in serving these
      purposes, and the briefings' perceived alignment (or conflict) with other
      priorities. Our findings illustrate the intrinsically rhetorical and variable
      nature of change.

PMID- 19853345
TI  - [Comments of article "Training of the plastic surgeon: Comparison of the French
      formation and the Canadian program of residence of the Royal College"].

PMID- 19853346
TI  - [Microsurgical nail reconstruction with free short-pedicle vascularized nail
      flap: about 13 cases].
AB  - This study was performed to review our 24-year experience in nail reconstruction
      with special attention to surgical technique, outcomes and cosmesis. A
      retrospective chart review of 13 toenail complexes transfers alone over a 24-year
      period was performed. The patients, nine men and four women, had an average age
      of 20 years (range, 2 to 38 years) at the time of surgery. Etiologies were trauma
      in 10 cases and tumor in three cases. The mean follow-up time was 13 years
      (range, 2 to 23 years). One nail flap necrosis occurred after surgery accounting
      for a complication rate of 8 %. Regarding nail cosmetic, the mean Foucher score
      was 15.4 points. Though nail reconstruction has been sometimes associated with
      complications and low cosmetic improvements, this study showed how microsurgery
      is able to reduce trauma issues.

PMID- 19853347
TI  - [Custom made chest-wall implant and Poland's syndrome: Between art and science].
AB  - Poland's syndrome is a well-described congenital thoracic deformity with mostly
      only an aesthetic damage. We report the case of a chest-wall correction of a
      young male patient by a custom made silicone implant, detailing the original
      process of manufacturing, and justifying the choice not to use a conventional
      technique of reconstruction. This alternative enhances the surgeon's therapeutic
      arsenal, so that he can provide a customized answer, adapted to the requirements
      and the morphological characteristics of each patient.

PMID- 19853348
TI  - [Horner syndrome due to first rib fracture].

PMID- 19853350
TI  - Neurologic recovery following cardiac arrest due to benzodiazepine and opiate
      toxicity.

PMID- 19853351
TI  - Cariporide given during resuscitation promotes return of electrically stable and
      mechanically competent cardiac activity.
AB  - Episodes of ventricular fibrillation (VF) and myocardial dysfunction commonly
      occur after cardiac resuscitation compromising the return of stable circulation.
      We investigated in a pig model of VF whether limiting Na(+)-induced cytosolic
      Ca(2+) overload using the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1)
      inhibitor cariporide promotes resuscitation with stable circulation. METHODS: VF
      was electrically induced in 20 male pigs and left untreated for 6 min after which
      CPR was initiated and continued for 8 min before attempting defibrillation. Pigs
      were randomized to receive 3-mg/kg cariporide (n=10) or 0.9%-NaCl (n=10) before
      chest compression. RESULTS: Seven of 10 pigs in each group were successfully
      resuscitated and survived 2h. Cariporide ameliorated post-resuscitation
      ventricular ectopic activity such that fewer singlets (5+/-5 vs. 26+/-21; p<0.05)
      and fewer bigemini (1+/-3 vs. 33+/-25; p<0.05) were observed during the initial 5
      min post-resuscitation. Additionally, cariporide-treated pigs did not require
      additional post-resuscitation shocks for ventricular tachycardia or recurrent VF
      (0.0+/-0.0 vs. 5.3+/-7.8 shocks; p=0.073). During the initial 60 min cariporide
      treated pigs had higher, cardiac index (6.1+/-0.7 vs. 4.4+/-1.1L/min/m(2);
      p<0.01), left ventricular stroke work index (45+/-9 vs. 36+/-10 gmm/beat/m(2);
      p<0.05), and numerically higher mean aortic pressure (104+/-11 vs. 91+/-12 mmHg;
      p=0.054). CONCLUSION: Cariporide administered at the start of chest compression
      may help restore electrically and mechanically stable circulation after
      resuscitation from cardiac arrest.

PMID- 19853352
TI  - Cold saline infusion and ice packs alone are effective in inducing and
      maintaining therapeutic hypothermia after cardiac arrest.
AB  - AIM OF THE STUDY: Hypothermia treatment with cold intravenous infusion and ice
      packs after cardiac arrest has been described and used in clinical practice. We
      hypothesised that with this method a target temperature of 32-34 degrees C could
      be achieved and maintained during treatment and that rewarming could be
      controlled. MATERIALS AND METHODS: Thirty-eight patients treated with hypothermia
      after cardiac arrest were included in this prospective observational study. The
      patients were cooled with 4 degrees C intravenous saline infusion combined with
      ice packs applied in the groins, axillae, and along the neck. Hypothermia
      treatment was maintained for 26 h after cardiac arrest. It was estimated that
      passive rewarming would occur over a period of 8h. Body temperature was monitored
      continuously and recorded every 15 min up to 44 h after cardiac arrest. RESULTS:
      All patients reached the target temperature interval of 32-34 degrees C within
      279+/-185 min from cardiac arrest and 216+/-177 min from induction of cooling. In
      nine patients the temperature dropped to below 32 degrees C during a period of 15
      min up to 2.5h, with the lowest (nadir) temperature of 31.3 degrees C in one of
      the patients. The target temperature was maintained by periodically applying ice
      packs on the patients. Passive rewarming started 26 h after cardiac arrest and
      continued for 8+/-3h. Rebound hyperthermia (>38 degrees C) occurred in eight
      patients 44 h after cardiac arrest. CONCLUSIONS: Intravenous cold saline infusion
      combined with ice packs is effective in inducing and maintaining therapeutic
      hypothermia, with good temperature control even during rewarming.

PMID- 19853353
TI  - Does heredity determine the allergy manifestation or the sensitisation to a
      specific allergen?
AB  - BACKGROUND: The role of genetics in allergy development is well accepted.
      However, studies could not delineate the mode of inheritance or what is
      specifically being inherited. The purpose of this study was to determine the
      effect of genetics on the development of allergy manifestation, serum IgE level,
      and sensitization to specific allergens. METHODS: Fifty-eight twin sets (age 7
      months to 11 years) were evaluated for allergy by medical history, family
      history, physical examination, serum total IgE level, and percutaneous testing to
      selected common allergens. RESULTS: In 25 monozygotic (MZ) sets, concordance of
      atopy was significantly higher than in 33 dizygotic (DZ) sets (84.6% vs 62.5%).
      The age at onset tended to be earlier when the mother was allergic than when the
      father was (23.5 months vs 30.5 months). When both twins were allergic, the intra
      pair difference in age at onset was within <6 months in 50% of MZ sets versus
      31.8% in DZ sets. Total IgE level in twins showed a very strong correlation in MZ
      sets (r 0.92), but only a moderate correlation among DZ sets (r 0.57). Skin test
      positivity to specific allergens did not show a significant concordance between
      twins in either group. CONCLUSION: Our study indicates that the genetic influence
      was strongest on the inheritance of IgE phenotype, the development of the atopic
      tendency, the age of onset, and to some extent on the specific allergy
      manifestation. The effect seemed less on determining the specific offending
      allergen(s), suggesting possible roles of epigenetic and environmental factors.

PMID- 19853354
TI  - Evaluation of phagocytes in atopic dermatitis.
AB  - BACKGROUND: Patients with atopic dermatitis frequently present recurrent
      infections by pyogenic bacteria or by intracellular microorganisms, suggesting an
      immune disorder. OBJECTIVE: Laboratorial investigation of phagocyte activity and
      chemotactic response by neutrophilic polymorphonuclear and mononuclear phagocytes
      in the peripheral blood of patients with atopic dermatitis from moderate to
      severe. METHODS: Through a transversal study, patients with atopic dermatitis
      from moderate to severe were selected. The neutrophilic and mononuclear
      phagocytes were separated and the phagocytic ingestion of zymosan particles was
      analysed, in addition to migration distance to the bacterial lipopolysaccharide
      chemotactic factor, comparing the results to the values obtained from healthy
      individuals within the same age group. RESULTS: Nineteen patients were selected,
      11 female and 8 male. The mean age was 6.47 years (+/-4.65). Among the 19
      patients studied, 14 (73.68%) presented a reduction in the neutrophilic and
      mononuclear phagocyte activity, with two (1.53%) patients presenting a reduction
      in the activity of both phagocytes. CONCLUSION: Our results demonstrated a
      reduction in chemotactic response and phagocytic activity by neutrophilic and/or
      mononuclear phagocytes in the majority of patients with atopic dermatitis from
      moderate to severe. Our results were coherent with the clinical data concerning
      the higher incidence of infections by pyogenic bacteria and fungi in patients
      with atopic dermatitis, which are microorganisms that require defence by the
      phagocytes researched in the present study.

PMID- 19853356
TI  - Sensitisation to aeroallergens among asthmatic and non-asthmatic adolescents
      living in a poor region in the Northeast of Brazil.
AB  - OBJECTIVES: To assess the kind and frequency of sensitisation to aeroallergens
      (skin prick test - SPT) of asthmatic and non-asthmatic adolescents (13-14 years
      old) living in the city of Caruaru, Northeast of Brazil, and to analyse their
      exposure to some environmental factors. METHOD: A case-control study was
      conducted with asthmatic (50) and non-asthmatic (150) adolescents diagnosed by
      the International Study of Asthma and Allergies in Childhood (ISAAC) written
      questionnaire. All were submitted to SPT with aeroallergens (house dust mites,
      cat and dog epithelium, cockroaches, moulds and grass) and completed a
      questionnaire to evaluate their environmental exposure. RESULTS: There were no
      significant differences between groups regarding gender, age, number of siblings
      and environmental exposure. Asthmatic subjects exhibited a higher frequency of
      positive SPTs than non-asthmatic subjects (54.0% vs 33.3%, p=0.009) mainly due to
      Periplaneta americana (34.0% vs 12.7%, p=0.0007 respectively) and Canis
      familiaris (20.0% vs 8.7%, p=0.029). CONCLUSION: Although sensitisation to
      aeroallergens was high among non-asthmatic adolescents, asthma was associated
      with parental history of atopic disease and sensitisation to P. americana and
      Canis familiaris but not to D. pteronyssinus showing that local studies are
      mandatory for the tailoring of appropriate management of allergic diseases.

PMID- 19853355
TI  - Neonatal sepsis and later development of atopy.
AB  - BACKGROUND: The role of infections on the development of atopy is still widely
      debated. We aimed to evaluate the effects of neonatal severe sepsis and
      consequent antibiotic treatment on the development of atopy and allergic
      diseases. MATERIAL AND METHODS: A retrospective enrollment at school age of
      children with a clear history of neonatal sepsis (NS) was performed from
      registers of neonatal intensive care units. A normal control was assigned to each
      patient with sepsis. Thirty six cases with sepsis (18 males, 18 females) and 36
      controls (21 males, 15 females) were selected (8.5+/-3.6 yrs). Physical
      examination and lung function evaluation were performed. Atopic status was
      verified by blood eosinophil count, total IgE serum level and skin prick tests
      (SPT). RESULTS: SPT positivity for at least one allergen was present in 30% of
      subjects in both groups. No difference for all investigated parameters between
      groups and no influence by other factors such as familiarity or gender was
      observed. No correlation was associated to NS history. CONCLUSIONS: Neonatal
      sepsis, even if clinically severe and dramatic, could represent an event too
      limited and really precocious in life to influence the development of immune
      response. Furthermore, other factors, besides infections, may influence the
      atopic future of newborns.

PMID- 19853357
TI  - A simple 3-day "rush" venom immunotherapy protocol: documentation of safety.
AB  - BACKGROUND: Venom immunotherapy (VIT) is the only effective treatment for
      hymenoptera hypersensitivity, but conventional protocols require a few weeks.
      OBJECTIVE: We present the safety of a 3-day "rush" protocol that requires only 7
      injections and 255 mgr cumulative dose before the 100 microg maintenance dose.
      METHODS: Forty-nine patients (33 males, 16 females) of mean age 43.57+/-12.9 yrs
      received "rush" VIT. Only 7 injections were required until the maintenance dose
      of 100 mgr was reached on Day 5. On Day 1, four injections were administered with
      initial dose of 5 mgr and total dose of 75 microg. On Day 3 a cumulative dose of
      180 mgr was administered in three injections (40 mgr, 60 mgr and 80 mgr). A dose
      of 100 mgr was administered on Day 5. Twenty-nine individuals were treated with
      Honey-Bee venom; 18 with Common wasp; 5 with Paper Wasp; while 13 patients
      received Mixed Vespid preparation. Inclusion criteria were documented IgE
      mediated allergy with intradermal sensitivity to < or =0.1 mgr/ml venom
      concentration and concomitant detection of specific venom IgE > or =0.35 kU/l.
      RESULTS: All patients reached the maintenance dose. Forty-nine patients received
      65 immunotherapy courses, resulting in 1520 injections. Thirty-three systemic
      reactions: 7 during building phase (1.5%); and 26 in the maintenance dose (2.4%)
      were observed in 9 patients. The percentage of reactions/total injection number
      was 2.2%; all reactions were mild-to-moderate. Fourteen patients reported
      documented field stings at least two months after VIT onset with only one
      reported mild systemic reaction. CONCLUSION: We propose a simple "rush" VIT
      protocol in an outpatient setting as an easy-to-perform alternative option for
      VIT induction phase.

PMID- 19853358
TI  - Contact allergy to propolis in beekeepers.
AB  - BACKGROUND: Allergy to propolis seems to be rare and little is known about it.
      OBJECTIVE: The aim of the study was to survey a subset of affected beekeepers to
      determine aspects such as time of onset of disease, comorbidity, and possible
      methods of prevention. METHODS: With the help of two German journals for
      beekeepers we contacted 41 beekeepers with propolis allergy. They were sent a
      questionnaire which assessed several aspects of the disease and was based on the
      current literature. RESULTS: 70.7% returned our questionnaire and had clear signs
      of propolis allergy with positive testing by their local allergologists. They
      reported that allergy had developed after an average of 9.5 years beekeeping. We
      also found a high prevalence of other allergies (72.4%). Interestingly, there
      were also systemic reactions to propolis in some beekeepers but not necessarily
      when using propolis as a medication against other diseases. Beekeepers believed
      that solvents used to clean the hands could play a role in the development of the
      disease. CONCLUSION: This study provides new insights into allergy to propolis.
      The hypothesis that solvents used to clean the hands could play a role in the
      development of the disease should be addressed in future studies.

PMID- 19853359
TI  - Persistence of cow's milk allergy beyond two years of age.
AB  - BACKGROUND: Cow's milk allergy (CMA) epidemiology seems to be changing over time,
      with an increase in prevalence and persistence. Our aim was to characterise a
      population of children with CMA beyond two years of age, followed up in a
      Paediatric Allergy Clinic at the tertiary care level. METHODS: Retrospective
      study of children with persistent CMA diagnosed from January 1997 to June 2006.
      Medical records were analysed regarding: clinical presentation, follow-up,
      treatment and acquisition of tolerance. Data analysis was performed using Excel
      2007 for Windows. RESULTS: Seventy-nine children were included, with mean age at
      first symptoms of 3 months. The symptoms were immediate in 93%, with cutaneous
      (87.3%), gastrointestinal (55.7%) and respiratory (25.3%) manifestations. During
      the follow-up period, 30% developed atopic eczema, 52% asthma and 35%
      rhinoconjunctivitis. A family history of atopy was identified in 53%. The
      majority presented increased serum total IgE (376+/-723 KU/l) and positive skin
      prick test (SPT) to cow's milk (CM) (79%). SPT to goat's milk was positive in 2/3
      of cases. Fifty-five percent had at least one accidental exposure to CM (severe
      reactions in 6%). During CM elimination diet, 35% were initially given an
      extensively hydrolysed formula, 17% a soy formula, and 48% both. By the age of 10
      years, 44% of children persisted with CMA. DISCUSSION: Our population of CM
      allergic children presented immediate symptoms with cutaneous expression in the
      majority. Severe reactions were common on accidental exposure. By the age of 10
      years, 44% maintained CMA, highlighting the importance of a multidisciplinary
      follow-up.

PMID- 19853360
TI  - The significance of toll-like receptors in human diseases.
AB  - Toll-like receptors (TLRs) are a family of transmembrane receptors that have been
      preserved throughout evolution and which selectively recognize a broad spectrum
      of microbial components and endogenous molecules released by injured tissue.
      Identification of these ligands by TLRs triggers signalling pathways which lead
      to the expression of numerous genes involved in a defensive response. In mammals,
      the products of these genes initiate inflammation, coordinate the effector
      functions of innate immunity, instruct and modulate adaptive immunity and
      initiate tissue repair and regeneration. Different mutations and experimental
      models which alter TLR function have revealed the significance of these receptors
      in susceptibility to infection and their involvement in the pathogenesis of a
      large number of non-infective inflammatory disorders such as cancer, allergy,
      autoimmunity, inflammatory bowel disease, or atherosclerosis. TLRs are currently
      viewed as important targets for the development of new vaccines and innovative
      therapies to prevent and treat human diseases.

PMID- 19853361
TI  - Process for European accreditation in Paediatric Allergology.
AB  - The present paper reviews the process by which the accreditation for the
      Paediatric Allergy specialty has been implemented in Europe according to the
      Section of Pediatrics Assembly of the European Academy of Allergy and Clinical
      Immunology. The itinerary by which the members of the Spanish Society of
      Pediatric Allergy and Clinical Immunology (SEICAP) have gained this accreditation
      and how it can be applied for in the future is also explained. Prospects for the
      future are also analysed.

PMID- 19853362
TI  - Premenopausal bleeding: When should the endometrium be investigated?--A
      retrospective non-comparative study of 3006 women.
AB  - OBJECTIVE: There is lack of consensus amongst professional organizations as
      regards the cut-off age for endometrial sampling of premenopausal women
      presenting with abnormal uterine bleeding (AUB) to exclude endometrial
      hyperplasia or carcinoma. Therefore we conducted this study to quantify the
      prevalence of hyperplasia and carcinoma in different age categories in
      premenopausal women with AUB to identify the appropriate cut-off age for
      endometrial sampling. STUDY DESIGN: A retrospective review of the histopathology
      reports of endometrial samples taken from 3006 women presenting with AUB and aged
      from > or =30 to < or =50 years at Ipswich Hospital, UK, from 1 January 1998 to
      31 December 2007. Women were divided into three subgroups according to age; group
      1: 30 to < or =40 (n=862), group 2: 40 to < or =45 (n=1035) and group 3: 45 to <
      or =50 (n=1109). RESULTS: Logistic regression revealed that the prevalence of
      atypical hyperplasia (OR: 3.85; 95% CI: 1.75, 8.49; p=0.01) and carcinoma (OR:
      4.03; 95% CI: 1.54, 10.5; p=0.04) was significantly higher in women in group 3
      when compared to younger women. There was no statistically significant difference
      as regards simple and complex hyperplasia in the different age categories. All
      but one of the women (n=23) who had complex atypical hyperplasia or carcinoma
      under the age of 45 years, presented with irregular rather than cyclical heavy
      menstrual bleeding. CONCLUSION: Our study, the largest in the literature,
      suggests using the age 45 years as a cut-off for sampling the endometrium in all
      women with AUB. However, irregular menstrual bleeding justifies investigating
      women regardless of their age.

PMID- 19853363
TI  - New insights into DNA-binding behavior of Wilms tumor protein (WT1)--a dual
      study.
AB  - Wilms Tumor suppressor protein (WT1) is a transcription factor that is involved
      in a variety of developmental functions during organ development. It is also
      implicated in the pathology of several different cancer forms. The protein
      contains four C(2)H(2)-type zinc fingers and it specifically binds GC-rich
      sequences in the promoter regions of its target genes, which are either up or
      down regulated. Two properties make WT1 a more unusual transcription factor - an
      unconventional amino acid composition for zinc finger 1, and the insertion of a
      tri-peptide KTS in some of the splice isoforms of WT1. Using six WT1 constructs
      in which zinc fingers are systematically deleted, a dual study based on a
      bacterial 1-hybrid system and surface plasmon resonance measurements is
      performed. The experiments show that the effect of zinc finger 1 is not
      significant in terms of overall DNA-binding kinetics, however it influences both
      the specificity of target recognition and stability of interaction in presence of
      KTS. The KTS insertion, however, only mildly retards binding affinity, mainly by
      affecting the on-rate. We suggest that the insertion disturbs zinc finger 4 from
      its binding frame, thus weakening the rate of target recognition. Finally, for
      the construct in which both zinc fingers 1 and 4 were deleted, the two middle
      fingers 2-3 still could function as a 'minimal DNA-recognition domain' for WT1,
      however the formation of a stable protein-DNA complex is impaired since the
      overall affinity was dramatically reduced mainly since the off-rate was severely
      affected.

PMID- 19853365
TI  - Photochemical model evaluation of the surface ozone impact of a power plant in a
      heavily industrialized area of southwestern Spain.
AB  - The characterization and evaluation of the impact that an industry is likely to
      have on the surrounding ozone levels is one of many problems confronting air
      quality managers and should be taken into consideration when authorizing its
      installation. The correct management of an environment, in terms of monitoring
      existing industries and planning new activities, requires adequate knowledge of
      the processes sustained by the industrial emissions therein. This paper explores
      the improvements in air quality management arising from taking into account the
      uncertainties involved in the photochemical modeling of the impact of an industry
      on surface ozone levels. For this, we evaluate the impact on ozone levels of a
      power plant located in an industrial area of southwestern Spain (Huelva). The
      evaluation takes into account the effects of both emissions' uncertainty and the
      non-linear chemistry between ozone and its precursors, thus providing a probable
      range of increase over the normative values (hourly and 8-hourly maximums)
      defined in the European Directive. The proposed methodology is easily applicable
      by air quality managers. Advanced modeling techniques were used for the power
      plant assessment, MM5 atmospheric modeling system, and air quality model CAMx.
      The results from meteorology and ozone forecasts have shown acceptable agreement
      with the observations. The spatial distribution of the impact is found to be
      strongly determined by mesoscale meteorological processes, which are reinforced
      by the local orography; there is also a marked temporal evolution. The industrial
      plume is observed to induce a decrease (or maintenance) of the ozone levels near
      the emission source (0-10km), and an increase in the ozone concentrations farther
      away (with maximums between 10 and 50km). In fact, in the meteorological episodes
      with a predominance of local breeze circulations, impacts have been detected at
      distances of more than 100km from the emission source. Sensitivity of the power
      plant impact to variations in ozone precursor emissions is described, and the
      scenarios and the points in the domain presenting higher sensitivity and
      registering larger impacts are also identified. The results show that the largest
      impacts take place in emission scenarios where the NO(x) has been reduced with
      respect to the base case scenario. In contrast, in scenarios where the VOC
      emissions are reduced with respect to the base case scenario, the impact is
      smaller or remains unchanged. This is important in areas like the study case,
      where there is a high percentage of biogenic VOC emissions and the industrial
      areas are close to natural protected areas and agricultural fields.

PMID- 19853364
TI  - CD44 expression is developmentally regulated in the mouse lens and increases in
      the lens epithelium after injury.
AB  - Hyaluronan is an oligosaccharide found in the pericellular matrix of numerous
      cell types and hyaluronan-induced signaling is known to facilitate fibrosis and
      cancer progression in some tissues. Hyaluronan is also commonly instilled into
      the eye during cataract surgery to protect the corneal endothelium from damage.
      Despite this, little is known about the distribution of hyaluronan or its
      receptors in the normal ocular lens. In this study, hyaluronan was found
      throughout the mouse lens, with apparently higher concentrations in the lens
      epithelium. CD44, a major cellular receptor for hyaluronan, is expressed
      predominately in mouse secondary lens fiber cells born from late embryogenesis
      into adulthood. Surgical removal of lens fiber cells from adult mice resulted in
      a robust upregulation of CD44 protein, which preceded the upregulation of alpha
      smooth muscle actin expression typically used as a marker of epithelial
      mesenchyma transition in this model of lens epithelial cell fibrosis. Mice
      lacking the CD44 gene had morphologically normal lenses with a response to lens
      fiber cell removal similar to wildtype, although they exhibited an increase in
      cell-associated hyaluronan. Overall, these data suggest that lens cells have a
      hyaluronan-containing pericellular matrix whose structure is partially regulated
      by CD44. Further, these data indicate that CD44 upregulation in the lens
      epithelium may be an earlier marker of lens injury responses in the mouse lens
      than the upregulation of alpha-smooth muscle actin.

PMID- 19853366
TI  - Analysis of arable land loss and its impact on rural sustainability in Southern
      Jiangsu Province of China.
AB  - Rapid urbanization and industrialization in southern Jiangsu Province have
      consumed a huge amount of arable land. Through comparative analysis of land cover
      maps derived from TM images in 1990, 2000 and 2006, we identified the trend of
      arable land loss. It is found that most arable land is lost to urbanization and
      rural settlements development. Urban settlements, rural settlements, and
      industrial park-mine-transport land increased, respectively, by 87 997 ha
      (174.65%), 81 041 ha (104.52%), and 12 692 ha (397.99%) from 1990 to 2006. Most
      of the source (e.g., change from) land covers are rice paddy fields and dryland.
      These two covers contributed to newly urbanized areas by 37.12% and 73.52% during
      1990-2000, and 46.39% and 38.86% during 2000-2006. However, the loss of arable
      land is weakly correlated with ecological service value, per capita net income of
      farmers, but positively with grain yield for some counties. Most areas in the
      study site have a low arable land depletion rate and a high potential for
      sustainable development. More attention should be directed at those counties that
      have a high depletion rate but a low potential for sustainable development. Rural
      settlements should be controlled and rationalized through legislative measures to
      achieve harmonious development between urban and rural areas, and sustainable
      development for rural areas with a minimal impact on the ecoenvironment.

PMID- 19853367
TI  - Factors affecting the implementation of green specifications in construction.
AB  - Green specifications constitute one of the important elements in green
      construction. New sustainability requirements and changing priorities in
      construction management have spurred the emerging green specifications to a
      faster pace of development. A cross-sectional survey has been conducted in Hong
      Kong in 2007 to identify principal factors leading to the success of preparing
      green specifications. Based on extensive construction management literature, 20
      variables concerning sustainable construction were summarized. Using the Mann
      Whitney U-test, the subtle differences between stakeholders in specifying
      construction work have been detected even with the high consistency of the
      responses among the groups. Moreover, five independent factors for successful
      specification of green construction have been categorized by factor analysis.
      They are related to (1) green technology and techniques, (2) reliability and
      quality of specification, (3) leadership and responsibility, (4) stakeholder
      involvement, and (5) guide and benchmarking systems. Whilst the first and fourth
      factors are generally more important, different stakeholder groups have different
      emphases. The results of the survey have been validated against established
      principles.

PMID- 19853368
TI  - Investigating biodiversity trajectories using scenarios--lessons from two
      contrasting agricultural landscapes.
AB  - Agriculture is the major land use at a global scale. In addition to food
      production, multifunctionality of landscapes, including values and ecosystem
      services like biodiversity, recreation and culture, is now focus for management.
      This study explores how a scenario approach, involving different stakeholders,
      may help to improve landscape management for biodiversity conservation. Local
      farmers and executives at the County Administrative Board were invited to discuss
      rural development and conditions for farmland biodiversity in two Swedish
      landscapes. The potential biodiversity for three future land use scenarios for
      the two landscapes was discussed: nature conservation, outdoor recreation and
      energy production, and compared with current and historical landscapes in each
      region. Analyses of habitat areas, connectedness and landscape diversity
      suggested that the energy and recreation scenarios had a negative impact on
      farmland biodiversity, whereas the nature conservation scenario, the current and
      historically reconstructed landscapes had a higher potential for biodiversity.
      The farmers appreciated the nature conservation scenario, but also the energy
      production scenario and they highlighted the need of increased subsidies for
      management of biodiversity. The farmers in the high production area were less
      interested in nature quality per se. The executives had similar opinions as the
      farmers, but disagreed on the advantages with energy production, as this would be
      in conflict with the high biodiversity and recreational values. The local
      physical and socio-economical conditions differ between landscapes and
      potentially shaped the stakeholders emotional attachment to the local
      environment, their opinions and decisions on how to manage the land. We stress
      the importance of incorporating local knowledge, visions and regional
      prerequisites for different land uses in conservation, since site and landscape
      specific planning for biodiversity together with a flexible subsidy system are
      necessary to reach the conservation goals within EU.

PMID- 19853369
TI  - Environmentally conscious manufacturing and product recovery (ECMPRO): A review
      of the state of the art.
AB  - Gungor and Gupta [1999, Issues in environmentally conscious manufacturing and
      product recovery: a survey. Computers and Industrial Engineering, 36(4), 811-853]
      presented an important review of the development of research in Environmentally
      Conscious Manufacturing and Product Recovery (ECMPRO) and provided a state of the
      art survey of published work. However, that survey covered most papers published
      through 1998. Since then, a lot of activity has taken place in EMCPRO and several
      areas have become richer. Many new areas also have emerged. In this paper we
      primarily discuss the evolution of ECMPRO that has taken place in the last decade
      and discuss the new areas that have come into focus during this time. After
      presenting some background information, the paper systematically investigates the
      literature by classifying over 540 published references into four major
      categories, viz., environmentally conscious product design, reverse and closed
      loop supply chains, remanufacturing, and disassembly. Finally, we conclude by
      summarizing the evolution of ECMPRO over the past decade together with the
      avenues for future research.

PMID- 19853370
TI  - Morphologic characterization of preoperatively treated prostate cancer: toward a
      post-therapy histologic classification.
AB  - BACKGROUND: Preoperative treatment of prostate cancer (PCa) changes morphology of
      residual tumors so that the Gleason score is no longer valid. OBJECTIVE: To
      codify morphologic features of preoperatively treated PCa and identify potential
      classifiers predictive of outcome. DESIGN, SETTING, AND PARTICIPANTS: We
      performed a detailed morphologic evaluation of specimens obtained from 115
      patients with high-risk PCa who had preoperative androgen ablation, alone or in
      combination with chemotherapy. MEASUREMENTS: Included hierarchical clustering
      analysis of morphologic characteristics, associations with other pathologic
      parameters, and univariate and multivariate analyses in search for associations
      with disease outcome. RESULTS AND LIMITATIONS: Based on hierarchical clustering
      analysis, we categorized pretreated prostate cancer in three morphologically
      distinct groups: group A, characterized by a predominance of cell clusters, cell
      cords, and isolated cells; group B tumors, by intact and fused small glands; and
      group C tumors by any degree of cribriform growth pattern or intraductal tumor
      spread. Univariate analysis identified associations between this grouping,
      pathologic tumor stage (p<0.01) and residual tumor volume (p<0.001). Presence of
      intraductal spread or cribriform pattern in biopsies was associated with group C
      tumors. The presence of cribriform or intraductal spread morphology and positive
      surgical margins were stronger predictors of biochemical relapse than pathologic
      stage on multivariate analysis. The number of specimens evaluated in this study
      was limited, and a prospective validation is warranted along with molecular
      studies to validate the proposed morphologic classifier. CONCLUSIONS: If
      validated, this classification will introduce uniformity in the selection of
      tissue samples for biomarker studies, facilitate the comparison of trials among
      different institutions, and may provide a new prognostic tool for preoperatively
      treated PCa.

PMID- 19853371
TI  - Re: Felix K. Chun, Alexandre de la Taille, Hendrik van Poppel, et al. Prostate
      cancer gene 3 (PCA3): development and internal validation of a novel biopsy
      nomogram. Eur Urol 2009;56:659-68.

PMID- 19853372
TI  - Re: Reinhold Zimmermann, Alin Cumpanas, Florin Miclea, Gunter Janetschek.
      Extracorporeal shock wave therapy for the treatment of chronic pelvic pain
      syndrome in males: a randomised, double-blind placebo-controlled study. Eur Urol
      2009;56:418-24.

PMID- 19853373
TI  - mTOR inhibitor rapamycin alone or combined with cisplatin inhibits growth of
      esophageal squamous cell carcinoma in nude mice.
AB  - Accumulating evidences have demonstrated that mTOR pathway has a central role not
      only in cell growth but also in invasion and metastasis of cancers. Here we
      reported that rapamycin or cisplatin alone inhibited significantly the tumor
      growth and their combination had the strongest anticancer effect on
      transplantable tumor growth of human ESCC cell line EC9706 in nude mice.
      Furthermore, western blots, RT-PCR and TUNEL assay revealed that rapamycin
      specifically blocked mTOR pathway and induced apoptosis of ESCC cells in vivo.
      These findings indicate a rationale for using mTOR inhibitors as a mechanism
      based therapeutic approach to patients with ESCC.

PMID- 19853374
TI  - Biosorption of Pb2+ from aqueous solutions by Moringa oleifera bark: equilibrium
      and kinetic studies.
AB  - Biosorption of Pb(2+) from aqueous solution by biomass prepared from Moringa
      oleifera bark (MOB), an agricultural solid waste has been studied. Parameters
      that influence the biosorption such as pH, biosorbent dose, contact time and
      concentration of metal ion were investigated. The experimental equilibrium
      adsorption data were tested by four widely used two-parameter equations, the
      Langmuir, Freundlich, Dubinin-Radushkevich (D-R) and Temkin isotherms. Results
      indicated that the data of Pb(2+) adsorption onto MOB were best fit by the
      Freundlich model. The adsorption capacity (Q(m)) calculated from the Langmuir
      isotherm was 34.6mgPb(2+)g(-1) at an initial pH of 5.0. Adsorption kinetics data
      were analyzed using the pseudo-first-, pseudo-second-order equations and
      intraparticle diffusion models. The results indicated that the adsorption kinetic
      data were best described by pseudo-second-order model. Infrared (IR) spectral
      analysis revealed that the lead ions were chelated to hydroxyl and/or carboxyl
      functional groups present on the surface of MOB. Biosorbent was effective in
      removing lead in the presence of common metal ions like Na(+), K(+), Ca(2+) and
      Mg(2+) present in water. Desorption studies were carried out with dilute
      hydrochloric acid for quantitative recovery of the metal ion as well as to
      regenerate the adsorbent. Based on the results obtained such as good uptake
      capacity, rapid kinetics, and its low cost, M. oleifera bark appears to be a
      promising biosorbent material for the removal of heavy metal ions from
      wastewater/effluents.

PMID- 19853375
TI  - Assessment of water contamination caused by a mutagenic textile effluent/dyehouse
      effluent bearing disperse dyes.
AB  - High performance liquid chromatography coupled to a diode array detector method
      was developed to detect disperse dyes in water samples over the range 0.50-35 ng,
      with detection limits of 0.09 ng, 0.84 ng and 0.08 ng, respectively, with good
      repeatability and accuracy. This study identifies the disperse azo dyes C.I.
      Disperse Blue 373, C.I. Disperse Orange 37 and Disperse Violet 93 as components
      of a commercial dye formulation assigned as Dispersol Black Dye (CVS) used in the
      textile industry for dyeing synthetic fibers that are contributing to the
      mutagenicity found in the Cristais River, Sao Paulo, Brazil. High performance
      liquid chromatography coupled to a diode array detector was applied to monitor
      the occurrence of these dyes in: (1) the treated industrial effluent, (2) raw
      river water, (3) treated river water, and (4) the sludge produced by a Drinking
      Water Treatment Plant (DWTP) which is located 6 km downstream from the textile
      industrial discharge, where dyes' concentrations changed from 1.65 ng L(-1) to
      316 microL(-1).

PMID- 19853376
TI  - Nitrobenzene-adsorption capacity of carbon materials released during the
      combustion of woody biomass.
AB  - The present study investigated the adsorptive ability of carbon materials (C1 and
      C2) released during the combustion of woody biomass. The physical and chemical
      properties, adsorption dynamics and adsorption isotherms of the adsorbents were
      compared with those of commercially available carbon that was powdered and
      activated. The percent nitrobenzene adsorption from an aqueous solution
      (nitrobenzene: 50mg/L) after 3h of adsorption using C1 was 92% compared with 81%
      when using the activated carbon powder. The saturated adsorption amounts of
      nitrobenzene were 294 mg/g for C1 and 344 mg/g for the activated carbon powder.
      However, the adsorption equilibrium constant for C1 was approximately 7-fold
      greater than that of the activated carbon powder. The methylene blue-adsorption
      capacity of C1 was similar to nitrobenzene adsorption. Thus, the results of the
      present study confirm that the carbon material resulting from the combustion of
      woody biomass is an inexpensive and environmentally friendly adsorbent for
      nitrobenzene.

PMID- 19853377
TI  - Investigation of accelerated and natural carbonation of MSWI fly ash with a high
      content of Ca.
AB  - The application of accelerated carbonation and natural carbonation to treat
      municipal solid waste incinerator (MSWI) fly ash was presented. The influence of
      reaction time and the liquid-to-solid (L/S) ratio, which both affect the
      reactivity of CO(2), was evaluated to determine their impact on the quality of
      carbonation. The optimum carbonation reaction of fly ash was found to occur when
      an L/S of 0.25 was used. Carbonation decreased the leaching of Pb, Cu, Zn and As,
      but increased the leaching of Cd and Sb. Based on the leaching of these six heavy
      metals, the optimum pH of the carbonated fly ash was 9.5-10.5. The release of
      soluble salts such as SO(4), Cl and F changed little following carbonation, and
      their release occurred independently of pH. The release potential and leaching
      behavior of carbonated fly ash were further evaluated using the three-step
      sequential extraction procedure proposed by the commission of the European
      Communities Bureau of Reference (BCR). The results of the BCR analyses revealed
      that carbonation exerted a significant effect on the heavy metal fractions in
      steps 1 and 2, but little effect on the distribution of heavy metals in step 3
      and residue fraction. Physical and chemical changes induced by carbonation were
      presented and discussed.

PMID- 19853378
TI  - Model AVSWAT apropos of simulating non-point source pollution in Taihu lake
      basin.
AB  - Accelerated eutrophication and nutrient loads in the lakes are of major concern
      for human health and environment. This study was undertaken for modeling the non
      point source pollution of Taihu lake basin in eastern China. The SWAT model
      having an interface in ArcView GIS was employed. Model sensitive parameters
      related to hydrology and water quality were obtained by sensitivity analysis, and
      then calibrated and validated by comparing model predictions with field data. The
      GIS showed good potential for parameterization of hill-slopes, channels, and
      representative slope profiles for SWAT model simulations. In a monthly and daily
      time step, the model's Nash-Sutcliffe coefficient (E) and the coefficient of
      determination (R(2)) indicated that values of simulated runoff, NH(4)(+)-N and
      total phosphorus were acceptably closer to the measured data. Surface water
      parameters especially CN, Soil-AWC and ESCO were the most sensitive and had more
      recognition in the model. It is concluded that runoff carrying N and P nutrients
      from chemical fertilizer inputs in agricultural areas is the major contributor to
      NPSP in the lake basin. So, decrease in excessive use of N and P fertilizers and
      their synergism with organic manures is recommended that would significantly
      reduce nutrient pollution in the lake ecosystem.

PMID- 19853379
TI  - The NALP1 inflammasome controls cytokine production and nociception in a rat
      fracture model of complex regional pain syndrome.
AB  - Tibia fracture followed by limb immobilization in rats evokes nociceptive and
      vascular changes resembling complex regional pain syndrome type I (CRPS I).
      Previously we observed that substance P (SP) and interleukin-1beta (IL-1beta)
      signaling contribute to chronic regional nociceptive sensitization in this model.
      It is known that inflammasome multi-protein complexes containing caspase-1 and
      NALP1 are involved in the activation of the IL-1beta family of pro-nociceptive
      cytokines expressed in skin and other tissues. Therefore, we hypothesized that SP
      activated inflammasomes might contribute to mechanical allodynia after fracture.
      Using this model we observed that: (1) inflammasome components and products
      NALP1, caspase-1, IL-1beta and IL-18 were present in low levels in normal skin,
      but expression of all these was strongly up-regulated after fracture, (2) NALP1,
      caspase-1 and IL-1beta were co-expressed in keratinocytes, and the number of
      NALP1, caspase-1, and IL-1beta positive cells dramatically increased at 4 weeks
      post-fracture, (3) LY303870, an NK1 receptor antagonist, effectively blocked
      fracture-induced up-regulation of activated inflammasome components and
      cytokines, (4) IL-1beta and IL-18 intraplantar injection induced mechanical
      allodynia in normal rats, and (5) both a selective caspase-1 inhibitor and an IL
      1 receptor antagonist attenuated fracture-induced hindpaw mechanical allodynia.
      Collectively, these data suggest that NALP1 containing inflammasomes activated by
      NK1 receptors are expressed in keratinocytes and contribute to post-traumatic
      regional nociceptive sensitization. These findings highlight the possible
      importance of neuro-cutaneous signaling and innate immunity mechanisms in the
      development of CRPS.

PMID- 19853380
TI  - The case for publishing 'negative' clinical trials.

PMID- 19853382
TI  - Immunization via the anal mucosa and adjacent skin to protect against respiratory
      virus infections and allergic rhinitis: a hypothesis.
AB  - Exposure of the immune system to environmental antigens and infectious agents by
      way of the anal mucosa and perianal skin could play an important role in
      protecting the respiratory tract against allergic conditions and virus
      infections. Hygienic practices that have reduced exposure of the immune system to
      such agents include the use of modern toiletry, disposable diapers and clothes
      dryers. Historically, the anal region was cleansed following defecation with
      natural materials that would have brought antigens and infectious agents from the
      environment into frequent contact with the perianal skin and anal mucosa. This
      practice was a crude form of transcutaneous and mucosal vaccination, whereby
      antigenic agents that are topically applied to skin or mucosal surfaces,
      penetrate into the tissues and stimulate immune responses that can extend to the
      respiratory tract. Furthermore, until the 1960s, diapers and other cloth items
      were often dried outdoors where they would have collected environmental antigens
      that, when applied to the body, could have made contact with the immune system in
      the skin. Herein, it is hypothesized that prevention of allergic rhinitis and
      possibly other disorders involving the immune system could be achieved by the
      daily application of preparations composed of environmental antigens and
      infectious agents to the anal mucosa and adjacent skin. In support of the
      proposal, immunotherapy for allergic rhinitis currently involves administration
      of specific allergens to subcutaneous tissue or to the sublingual mucosa. It is
      considered that superior protection could be achieved by applying the allergens
      to the anal region where they would target the immune system in both mucosal
      tissue and adjacent skin. It is also hypothesized that respiratory viruses
      applied to the anal region would infect tissues at that site and induce immune
      responses that would protect the respiratory tract against the common cold and
      influenza. This approach is supported by evidence that orally administered
      adenovirus vaccine can induce an infection in the intestinal mucosa that
      stimulates immunity to protect the respiratory tract. Although other respiratory
      viruses are unlikely to survive passage through the intestinal tract, rhinovirus
      has on rare occasion been detected in stool specimens, suggesting the possibility
      of an infection at the terminal end of the digestive tract. Respiratory syncytial
      viruses and influenza viruses are amenable to modification by reverse genetics
      and other techniques and it is expected that natural or modified viruses applied
      to the anal region could serve to immunize the respiratory tract.

PMID- 19853383
TI  - Is pituitary failure the real therapeutic target in septic shock?
AB  - Severe sepsis and septic shock have been part of intensivists' major challenges
      since the birth of the specialty. This clinical picture is followed by the
      development of a multiple organ failure syndrome. Our working hypothesis today is
      that multiple organ failures develop due to a systemic intravascular malignant
      inflammatory response. This article proposes an alternative understanding of the
      problem based on some of the recent data and understandings of non glycemic, non
      insulinemic endocrine dysfunction in severe sepsis and septic shock. Our
      presentation of selected literature supports the presence of a decreased
      production and activity in steroids, thyroid hormones, growth hormone,
      vasopressin and prolactin in septic shock. These hormones have important and
      synergistic functions. The disruption of which can lead to multiple organ failure
      in septic shock. Developing research focusing on the broad hypothalamic and
      pituitary functions could improve our understanding of metabolic derangements in
      severe sepsis and septic shock and thus provide new therapeutic options. These
      new therapies based on hormonal replacement are currently available at low cost
      and could improve outcomes.

PMID- 19853384
TI  - Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma
      with sarcomatous features - "Ependymosarcoma".
AB  - By analogy to gliosarcoma, the term "ependymosarcoma" has recently been coined to
      thematize the rare phenomenon of a malignant mesenchymal component arising within
      an ependymoma. We report on an example of this paradigm, involving tanycytic
      ependymoma as the host tumor in a 40-year-old female who underwent two tumor
      extirpation procedures at one-year interval. She first presented with severe
      headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5cm in
      diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus.
      Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells
      that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic
      activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A
      histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and
      no adjuvant therapy given. At recurrence, the lesion was 3.5cm in diameter,
      intensely enhancing, and had already seeded into the subarachnoid space.
      Histology showed a biphasic glial-sarcomatous architecture with remnants of the
      original ependymoma now displaying hypercellularity and atypical - yet not
      frankly anaplastic - features. The sarcomatous moiety consisted of spindle and
      epithelioid cells densely interwoven with reticulin fibers. While the ependymal
      component was GFAP and S100 protein positive, and featured punctate staining for
      EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the
      latter reacted for vimentin and smooth muscle actin. To the best of our
      knowledge, this is the first documentation of tanycytic ependymoma undergoing
      malignant transformation, one driven by a highly anaplastic mesenchymal
      component, corresponding to "ependymosarcoma".

PMID- 19853381
TI  - Peripheral and central sensitization in remote spinal cord regions contribute to
      central neuropathic pain after spinal cord injury.
AB  - Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is
      described by the region affected: above-level, at-level and below-level pain
      occurs in dermatomes rostral, at/near, or below the SCI level, respectively.
      People with SCI and rodent models of SCI develop above-level pain characterized
      by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain
      are unknown and the goals of this study were to elucidate components contributing
      to the generation of above-level CNP. Following a thoracic (T10) contusion,
      forelimb nociceptors had enhanced spontaneous activity and were sensitized to
      mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical
      dorsal horn neurons showed enhanced responses to non-noxious and noxious
      mechanical stimulation as well as thermal stimulation of receptive fields.
      Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating
      transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal
      damage as a cause for above-level sensitization since few C8 DRG cells expressed
      AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally,
      activated microglia and astrocytes were present in thoracic and cervical cord at
      35 days post-SCI, indicating a rostral spread of glial activation from the injury
      site. Based on these data, we conclude that peripheral and central sensitization
      as well as reactive glia in the uninjured cervical cord contribute to CNP. We
      hypothesize that reactive glia in the cervical cord release pro-inflammatory
      substances which drive chronic CNP. Thus a complex cascade of events spanning
      many cord segments underlies above-level CNP.

PMID- 19853385
TI  - [Asphyxiating thoracic dysplasia (Jeune syndrome): about two cases].
AB  - Asphyxiating thoracic dysplasia (Jeune syndrome) is an osteochondrodysplasia with
      autosomal recessive inheritance, characterised by a nanism with rhizomelic
      predominance, associated with a narrow thorax. It induces an alteration of the
      respiratory function that conditions the prognosis, which is worsened in case of
      associated visceral lesions (probably related to mutations of genes implicated in
      ciliary development, as recently described). We report the observation of two
      severe cases of Jeune syndrome to emphasize the advancement of imaging,
      especially echography, and molecular biology in establishing prenatal diagnosis
      as well as prognosis of this syndrome.

PMID- 19853387
TI  - [Continuous medical evaluation in a gynaecological and obstetrical unit: Our
      experience about scheduled caesarean].
AB  - Continuous medical evaluation (CME) is compulsory which aims to ameliorate and
      guarantee quality of care. This paper describes the experience of our unit during
      the different stages of evaluation that permit us to obtain our accreditation.
      Our evaluation dealt with the "amelioration of women's and newborn's care after
      scheduled caesarean section". A first retrospective study of files of scheduled
      caesareans allowed to update possible points of improvement, after application of
      adapted corrective actions, both at the medical and paramedical level. The second
      study, made after application of these actions, allowed to appreciate the results
      of our initiative of CME, to update new possible points of improvement, but also
      to notice certain limits in the achievement of the objectives.

PMID- 19853386
TI  - [Atypical epithelial hyperplasia of the breast: current state of knowledge and
      clinical practice].
AB  - INTRODUCTION: The diagnosis of atypical epithelial hyperplasia (AEH) increases
      with breast cancer screening. AEH is divided in three groups: atypical ductal
      hyperplasia, columnar cell lesions with atypia, lobular neoplasia. The management
      of women with AEH is not consensual because of uncertainty about their diagnosis
      related to the type of the biopsy sampling (core needle biopsy or surgical
      excision) and their controversial clinical signification between risk marker and
      true precursor of breast cancer. MATERIAL AND METHODS: A systematic review of
      published studies was performed. Medline baseline interrogation was performed
      with the following keywords: atypical ductal hyperplasia, columnar cell lesions
      with atypia, lobular neoplasia, core needle biopsy, breast cancer, precursor
      lesion, hormonal replacement therapy. For each breast lesion, identified
      publications (English or French) were assessed for clinical practise in
      epidemiology, diagnosis and patient management. RESULTS: With
      immunohistochemistry and molecular studies, AEH seems to be precursor of breast
      cancer. But, epidemiological studies show low rate of breast cancer in women with
      AEH. AEH were still classified as risk factor of breast cancer. CONCLUSION:
      Because of high rate of breast cancer underestimation, surgical excision is
      necessary after the diagnosis of AEH at core needle biopsy. Surgical oncology
      rules and collaboration with radiologist are required for this surgery. A second
      operation was not required due to involved margins by AEH (except with
      pleiomorphic lobular neoplasia) because local control of breast cancer seems to
      be unchanged. Besides, hormonal replacement therapy for patient with AEH is not
      recommended because of lack of studies about this subject.

PMID- 19853388
TI  - Phylogenetic identification of Aeromonas simiae from a pig, first isolate since
      species description.
AB  - The species Aeromonas simiae was first described on the basis of two strains (CIP
      107798(T) and CIP 107797) isolated from faeces of healthy monkeys (M.
      fascicularis) from Mauritius, which were kept in quarantine in the Centre for
      Primatology, Louis Pasteur University, Strasbourg, France. In the present study,
      during a survey to determine the prevalence of Aeromonas at three different pig
      slaughterhouses at north of Portugal, a single strain MDC2374 (out of 703
      isolates) was identified as A. simiae on the basis of 16S rDNA, gyrB and rpoD
      sequencing, confirming that traditional biochemical approaches are not resolute
      to identify rarely isolated Aeromonas species. To our knowledge, this is the
      first time since species description that A. simiae is newly isolated and
      identified.

PMID- 19853389
TI  - Peripheral arterial disease in women.
AB  - Peripheral arterial disease (PAD) is chronic arterial occlusive disease of the
      lower extremities caused by atherosclerosis whose prevalence increases with age.
      Only one-half of women with PAD are symptomatic. Symptomatic and asymptomatic
      women with PAD are at increased risk for all-cause mortality, cardiovascular
      mortality, and mortality from coronary artery disease. Modifiable risk factors
      that predispose women to PAD include active cigarette smoking, passive smoking,
      diabetes mellitus, hypertension, dyslipidemia, increased plasma homocysteine
      levels and hypothyroidism. With regard to management, women who smoke should be
      encouraged to quit and referred to a smoking cessation program. Hypertension,
      diabetes mellitus, dyslipidemia, and hypothyroidism require treatment. Statins
      reduce the incidence of intermittent claudication and improve exercise duration
      until the onset of intermittent claudication in women with PAD and
      hypercholesterolemia. Anti-platelet drugs such as aspirin or especially
      clopidogrel, angiotensin-converting enzyme inhibitors and statins should be given
      to all women with PAD. Beta blockers are recommended if coronary artery disease
      is present. Exercise rehabilitation programs and cilostazol increase exercise
      time until intermittent claudication develops. Chelation therapy should be
      avoided as it is ineffective. Indications for lower extremity percutaneous
      transluminal angioplasty or bypass surgery in women are (1) incapacitating
      claudication interfering with work or lifestyle; and (2) limb salvage in women
      with limb-threatening ischemia as manifested by rest pain, non-healing ulcers,
      and/or infection or gangrene. Future research includes investigation of
      mechanisms underlying why women have a higher risk of graft failure and major
      amputation.

PMID- 19853390
TI  - Techniques for siding manual phalanges.
AB  - Identifying the anatomical origin of skeletal elements is a basic and important
      part of a forensic anthropological investigation, but techniques for determining
      the side and ray of the phalanges are conspicuously scarce in the physical
      anthropology literature. Features of particular phalanges are important to
      aspects of archaeological and paleoanthropological studies, as well as for
      identification and trauma analysis in forensic cases. Correct siding of phalanges
      may therefore be quite critical in certain contexts. This study evaluates several
      siding techniques previously developed and/or described in a recent study by Case
      and Heilman (2000). Unlike in their study where observers were provided all
      phalange positional information except for side, observations in this study were
      undertaken with no positional information provided thus making the examinations
      more similar to those performed in a forensic context. Tests of phalange siding
      techniques were carried out on two skeletal samples: the Terry Collection at the
      Smithsonian's National Museum of Natural History where the ray and side of
      phalanges are documented and phalange collections are often complete, and the
      Bass Collection at the University of Tennessee where phalange positional
      information is undocumented and where phalange collections are seldom complete.
      The features described by Case and Heilman were found to work quite well. In the
      documented (Terry) sample, there was a high rate of correct siding, up to 100%
      for several phalanges. In the undocumented (Bass) sample, the features could be
      used to side the phalanges to a reasonable degree of certainty, and certainty
      increased when both sides of a particular phalange were present. Finally, several
      other useful siding and ray identification features were identified.

PMID- 19853391
TI  - Forensic age estimation of living individuals: a retrospective analysis.
AB  - In recent years, skeletal age determination has become increasingly important in
      criminal investigations for determining the age of living individuals. To
      increase diagnostic accuracy, a physical examination, an X-ray examination of the
      left hand, as well as a dental examination including the determination of the
      dental status and an X-ray of the dentition should always be performed. In this
      work, the authors analyze a sample of 52 illegal immigrants who came under their
      observation in the period from May 1989 to September 2007. A statistical analysis
      of the results of dental and skeletal age estimations was performed as well as an
      analysis between the reported and assessed ages. The results showed a significant
      difference between reported age and assessed biological age (p<0.001); however,
      no statistical difference was shown between skeletal and assessed dental age
      (p=0.431).

PMID- 19853392
TI  - Degradation of N-hydroxy-3,4-methylenedioxymethamphetamine in aqueous solution
      and its prevention.
AB  - N-Hydroxy-3,4-methylenedioxymethamphetamine (N-OH-MDMA) is a lesser known
      psychedelic drug that has recently circulated in the Japanese illicit drug
      market. From the instability of the similarly structured N-hydroxy-3,4
      methylenedioxyamphetamine (N-OH-MDA) in neutral-to-basic aqueous solution, it was
      presumed that N-OH-MDMA would also degrade in aqueous solution. The aims of this
      study were: (i) investigation of the degradation of N-OH-MDMA in aqueous solution
      and its prevention, (ii) identification of the degradation products, (iii)
      determination of the pKa for the conjugate acid of N-OH-MDMA, and (iv) evaluation
      of liquid-liquid extraction recovery. N-OH-MDA was also included in some of these
      studies. N-OH-MDMA degraded to 14.9% of initial concentration after 2 h storage
      in pH 10 buffer solution at 22 degrees C. This degradation was completely
      inhibited at least for 2 h by addition of L-ascorbic acid, a strong reactive
      oxygen scavenger. These findings indicate that reactive oxygen species in
      alkaline solution were involved in N-OH-MDMA degradation. N-OH-MDA, alpha-methyl
      (N-methylene)-3',4'-methylenedioxybenzeneethanamine and 3',4'
      methylenedioxyphenyl-2-propanone oxime were found as degradation products of N-OH
      MDMA in alkaline solution. The pKa for the conjugate acid of N-OH-MDMA was
      determined by titration to be 5.52, which was much lower than that reported for
      3,4-methylenedioxymethamphetamine (pKa=10.38). Excellent recoveries for N-OH-MDMA
      and N-OH-MDA (>98%) were achieved by extraction with ethyl acetate or chloroform
      from a basic buffer (pH 10) solution containing 0.1% L-ascorbic acid.

PMID- 19853393
TI  - Current management of febrile seizures in Japan: an overview.
AB  - Febrile seizures (FS) require both acute and chronic management. Acute management
      includes the treatment and differential diagnosis of FS and depend on the
      presence of seizures and a patient's level of consciousness upon arrival at
      hospital: a patient may be discharged after physical examination if there are no
      seizures and no alteration of consciousness; close observation and laboratory
      examinations may be indicated in cases when there are no seizures but the patient
      exhibits altered consciousness; and intravenous diazepam (DZP) is indicated if
      seizures persist. Central nervous system infections should be ruled out: if the
      patient has signs of meningeal irritation or increased intracranial pressure,
      disturbed consciousness for >1h, atypical seizures (partial seizures, seizures
      for >15 min, or recurrent seizures within 24h), cerebrospinal fluid examinations
      and/or computed tomography/magnetic resonance imaging are warranted. Chronic
      management includes the prevention of recurrent FS, counseling parents, and
      vaccination. Japanese guideline for the prevention of recurrent FS defines two
      types of warning factors (WF) for selecting patients who should be monitored
      carefully: factors related to the onset of epilepsy (EP factors) and recurrence
      of FS (FS factors). The EP factors consist of neurological or developmental
      abnormalities prior to the onset of FS, atypical seizures, and history of
      epilepsy in parents or siblings. The FS factors include the onset of FS before 1
      year of age and a history of FS in one or both parents. The guideline recommends
      no medication for children with two or fewer past episodes of FS without WF;
      prophylactic DZP for children with prolonged FS exceeding 15 min, or two or more
      episodes of FS with two or more WF; and daily administration of phenobarbital or
      valproate for children in whom FS occur under 38 degrees C or who have prolonged
      FS despite prophylactic DZP. To reduce parents' anxiety, the natural history of
      FS should be explained. A child can be given all current vaccinations 2-3 months
      after the last episode of FS by his/her family doctor with information provided
      to the parents as to how to cope with fever and convulsions.

PMID- 19853394
TI  - [Cystic duct cyst: what about Todani's VI?].

PMID- 19853395
TI  - Impact of stereotactic 11-g vacuum-assisted breast biopsy on cost of diagnosis in
      Austria.
AB  - PURPOSE: To determine the frequency with which stereotactic 11-g vacuum-assisted
      breast biopsy (11-g SVAB) obviates an open surgical biopsy (OSB), to compare the
      costs of these two biopsy methods, and to estimate the potential cost savings
      attributable to 11-g SVAB in the diagnosis of suspicious breast lesions in
      patients in Austria. MATERIALS AND METHODS: We retrospectively reviewed 318
      consecutive breast lesions of BI-RADS categories IV and V (microcalcifications
      n=166; masses n=152) on which 11-g SVAB and OSB were performed. Cost savings were
      calculated using nationally allowed flat rates and patient charges. Costs were
      measured from a hospital and a socioeconomic perspective. Common clinical
      scenarios and sensitivity analyses assessed the extent of achievable cost
      savings. RESULTS: 11-g SVAB obviated the need for an OSB in 93 (29%) of 318
      women. Overall cost savings per 11-g SVAB over OSB were ? 242 per case from a
      hospital perspective, and ? 422 per case from a socioeconomic perspective. The
      use of 11-g SVAB decreased the cost of diagnosis by 7% from a hospital
      perspective, and by 10% from a socioeconomic perspective. CONCLUSION: In Austria,
      annual national savings of over 5 million Euro could be realized with the use of
      11-g SVAB for the diagnosis of suspicious breast lesions. Although savings per
      case are modest, the national health care system realizes significant cost
      reduction as women benefit from a faster and less invasive approach to diagnosis.

PMID- 19853396
TI  - To be or not to be: significance of lymph nodes on pretreatment CT in predicting
      survival of rectal cancer patients.
AB  - PURPOSE: To assess the extent to which pretreatment imaging of lymph nodes by
      computed tomography (CT) predicts survival of patients with rectal cancer.
      MATERIALS AND METHODS: We retrospectively analyzed 70 patients with rectal
      cancer, who had pretreatment CT and curative surgery between December 1999 and
      October 2003. These patients were followed until December 2007, ensuring minimal
      follow-up time of 49 months. Two radiologists who reviewed the CT images on
      workstations had no prior access to clinical and treatment information regarding
      the selected patients. The parameters assessed for survival analysis were as
      follows: patient age, sex, CEA and CA199 level, preoperational therapy, tumor
      location, serosal invasion, largest diameters and numbers of lymph nodes on
      pretreatment CT. Kaplan-Meier survival curves, the log-rank test, and the
      multivariate Cox proportional hazards model were used to evaluate the prognostic
      value of the parameters. RESULTS: Using pretreatment CT as prognostic tool, we
      found that both size and number of lymph nodes correlated with the overall
      survival of patients with rectal cancer. The data proved that a diameter smaller
      than 8mm for the largest lymph node was correlated with prolonged survival (P <
      0.001). Meanwhile, patients with more than 4 lymph nodes had a significantly
      worse disease-specific survival (P = 0.042). Both parameters are independent
      prognostic factors (hazard ratio 4.910 and 3.563) and could predict the overall
      survival of rectal cancer patients. CONCLUSION: The lymph node size and number,
      as determined by pretreatment CT, is an important clinical prognostic factor in
      patients with rectal cancer. The pretreatment CT findings could be used to
      predict survival and plan appropriate therapies.

PMID- 19853397
TI  - Performance qualification of an electronic tongue based on ICH guideline Q2.
AB  - Recent progress in sensor technology has led to the development and application
      of electronic taste sensing systems. Especially taste prediction of
      pharmaceutical formulations is a matter of particular interest and is
      increasingly performed using electronic tongues. Several studies have dealt with
      electronic tongues before, but an analytical approach describing successfully
      conducted qualification has not been reported yet. Performance qualification of
      the taste sensing system SA402B (Insent Inc., Atsugi-chi, Japan) equipped with
      seven lipid membrane sensors was undertaken with special regard to bitter taste
      assessment. These sensors represent the gustatory stimuli bitterness, umami,
      saltiness, sourness, and the nociceptive sensation astringency. Specificity,
      linearity, range, accuracy, precision, detection and quantitation limit as well
      as robustness were established for each sensor type referring to ICH guideline Q2
      (R1). Some items mentioned in the guideline were applicable whereas others had to
      be modified due to differences of the system to other commonly used analytical
      techniques. Quinine hydrochloride being one of the bitterest drugs served as
      model substance. A large range of linearity (0.01-100mM) with corresponding
      precision (RSD<4%) was found for most sensors. One sensor had a lower detection
      threshold (0.0025mM) for quinine hydrochloride than humans typically have.
      Different methods for determination of detection and quantitation limits were
      implemented and discussed with respect to rationality and feasibility. Therefore
      the approach based on visual evaluation was found as most adequate. An adapted
      guidance following ICH guideline Q2 was developed serving qualification of taste
      sensing systems in the future.

PMID- 19853398
TI  - Interaction of kaempferol with human serum albumin: a fluorescence and circular
      dichroism study.
AB  - The interaction of kaempferol (kaemp), a natural flavonoid to which
      antioxidative, anti-inflammatory and cardio-protective biological activities have
      been attributed, with human serum albumin (HSA), the main in vivo transporter of
      exogenous substances, was investigated by steady-state, synchronous fluorescence
      and circular dichroism spectroscopies. The binding constant, K, and number of
      binding sites, n, were computed using literature models that showed satisfactory
      agreement and revealed a strong interaction (K approximately 3.5x10(5)M(-1), n
      approximately 1). The binding process was investigated at temperatures in the
      range 298-313K, allowing for the evaluation of the thermodynamic parameters,
      which indicate the occurrence of hydrogen bonding interactions. The distance
      between kaemp and the tryptophan residue of HSA was estimated at 2.7nm using
      Forster's theory of nonradiative resonance energy transfer. Using circular
      dichroism we evidenced some degree of HSA defolding upon binding.

PMID- 19853399
TI  - Disease-specific education in the primary care setting increases the knowledge of
      people with chronic obstructive pulmonary disease: a randomized controlled trial.
AB  - OBJECTIVE: To examine the effect of brief disease-specific education delivered in
      primary care on objective measures of knowledge in individuals recently diagnosed
      with chronic obstructive pulmonary disease (COPD). METHODS: A randomized control
      trial was undertaken during which an experimental group received 2h of education
      delivered by a certified COPD educator and a control group received usual care.
      The Bristol COPD Knowledge Questionnaire (BCKQ) was self-administered at the time
      of randomization and approximately three months later. RESULTS: Of the 93
      individuals that completed the study, 50 (forced expiratory volume in 1s
      [FEV(1)]=60.0+/-14.3% predicted; 22 males) and 43 (FEV(1)=58.2+/-14.4% predicted;
      20 males) participants were randomized to the experimental and control groups,
      respectively. The BCKQ increased from 27.6+/-8.7 to 36.5+/-7.7 points (p<0.001)
      in the experimental group, which was greater than any seen in the control group
      (between-group difference 8.3, 95% confidence interval 5.5-11.2 points).
      CONCLUSION: As little as 2h of education delivered in primary care was effective
      at increasing objective measures of disease-specific knowledge. PRACTICE
      IMPLICATIONS: A program of brief education delivered in the primary care setting,
      represents an important approach for many individuals with COPD who are unlikely
      to access pulmonary rehabilitation.

PMID- 19853400
TI  - Management of diabetic foot problems.
AB  - BACKGROUND: Diabetic foot problems and their complications are a medical and
      economic challenge to the health care system and require an aggressive
      multidisciplinary approach to achieve limb salvage. The goals of this review
      article are to delve into this comprehensive topic and summarize key points
      regarding diabetic foot problems from the perspective of the vascular specialist
      treating these patients. METHODS: The MEDLINE database was searched to identify
      articles on this topic. RESULTS: We found 112 relevant articles. These were used
      to provide current data on (1) the pathogenesis leading to diabetic foot lesions
      (ie, the etiologic triad of ischemia, neuropathy, and infection), (2) the
      clinical presentation of these foot lesions and their systemic manifestations,
      (3) the optimal methods of diagnostic evaluation, including noninvasive testing
      and arteriography, (4) treatment selection guidelines to help delineate which
      patients require revascularization, and (5) medical and interventional
      treatments, including prevention strategies, wound healing strategies, use of
      antibiotics, and endovascular and open surgical options for revascularization.
      CONCLUSIONS: The data presented in this review article allow vascular clinicians
      to optimize patient care and achieve effective limb salvage for this growing
      segment of the population.

PMID- 19853401
TI  - Postoperative renal function preservation with nonischemic femoral arterial
      cannulation for thoracoabdominal aortic repair.
AB  - BACKGROUND: Renal failure after thoracoabdominal aortic repair is a significant
      clinical problem. Distal aortic perfusion for organ and spinal cord protection
      requires cannulation of the left femoral artery. In 2006, we reported the finding
      that direct cannulation led to leg ischemia in some patients and was associated
      with increased renal failure. After this finding, we modified our perfusion
      technique to eliminate leg ischemia from cannulation. In this article, we present
      the effects of this change on postoperative renal function. METHODS: Between
      February 1991 and July 2008, we repaired 1464 thoracoabdominal aortic aneurysms.
      Distal aortic perfusion was used in 1088, and these were studied. Median patient
      age was 68 years, and 378 (35%) were women. In September 2006, we began to adopt
      a sidearm femoral cannulation technique that provides distal aortic perfusion
      while maintaining downstream flow to the leg. This was used in 167 patients
      (15%). We measured the joint effects of preoperative glomerular filtration rate
      (GFR) and cannulation technique on the highest postoperative creatinine level,
      postoperative renal failure, and death. Analysis was by multiple linear or
      logistic regression with interaction. RESULTS: The preoperative GFR was the
      strongest predictor of postoperative renal dysfunction and death. No significant
      main effects of sidearm cannulation were noted. For peak creatinine level and
      postoperative renal failure, however, strong interactions between preoperative
      GFR and sidearm cannulation were present, resulting in reductions of
      postoperative renal complications of 15% to 20% when GFR was <60 mL/min/1.73
      m(2). For normal GFR, the effect was negated or even reversed at very high levels
      of GFR. Mortality, although not significantly affected by sidearm cannulation,
      showed a similar trend to the renal outcomes. CONCLUSION: Use of sidearm
      cannulation is associated with a clinically important and highly statistically
      significant reduction in postoperative renal complications in patients with a low
      GFR. Reduced renal effect of skeletal muscle ischemia is the proposed mechanism.
      Effects among patients with good preoperative renal function are less clear. A
      randomized trial is needed.

PMID- 19853402
TI  - A giant femoral artery pseudoaneurysm in an infant boy.

PMID- 19853403
TI  - Balloon expandable stents facilitate right renal artery reconstruction during
      complex open aortic aneurysm repair.
AB  - OBJECTIVE: Patients undergoing repair of thoracoabdominal (TAA) or visceral
      aortic segment aneurysms typically require reconstruction of the renal arteries.
      The use of balloon expandable stents (BES) has been proposed as an alternative to
      endarterectomy or bypass for renal artery reconstruction (RAR) during open aortic
      aneurysm repair. We report technical aspects and long-term patency data for this
      method of right RAR during complex open aortic aneurysm repair. METHODS: During
      the interval July 1, 2005 to December 31, 2007, a total of 67 patients underwent
      right RAR using a BES during concomitant TAA (type I: n = 2 [2.9%], type II: n =
      8 [11.9%], type III: n = 13 [19.4%], and type IV: n = 22 [32.8%]), juxtarenal (n
      = 9 [13.4%]) or suprarenal (n = 13 [19.4%]) AAA repair. Indications for RAR were
      orificial stenosis (n = 21 [31%]) and/or technical considerations referable to
      the proximal aortic suture line. Patency of the renal stent was evaluated in
      patients with computed tomography angiography using three-dimensional
      reconstruction or with abdominal duplex evaluation at follow-up. RESULTS: The
      mean patient age was 75.1 years, 54.4% were male, and 18% of operations were in
      nonelective circumstances. Twenty-seven (39%) out of 67 patients had a
      preoperative creatinine level > or = 1.4 mg/dL. Two patients (2.9%) developed
      permanent renal failure postoperatively (neither related to renal artery
      occlusion). Mean radiologic follow-up was 405 days (11-1281) with 98% stent
      patency noted. One patient had an early stent occlusion noted at 1 month. An
      additional patient was noted to have a nonflow-limiting dissection distal to the
      renal stent, and another was noted to have distal migration of the stent beyond
      the renal ostium; however, these findings were clinically silent. CONCLUSIONS:
      The use of BES during complex open aortic aneurysm repair affords a rapid and
      durable mode of RAR, obviating the need for endarterectomy and its associated
      technical complications.

PMID- 19853404
TI  - Keratoconus, cross-link-induction, comparison between fitting exponential
      function and a fitting equation obtained by a mathematical model.
AB  - With reference to experimental data in the literature, we present a model
      consisting of two elastic elements, conceived to simulate resistance to
      stretching, at constant velocity of elongation, of corneal tissue affected by
      keratoconus, treated with riboflavin and ultraviolet irradiation to induce cross
      linking. The function describing model behaviour adapted to stress and strain
      values. It was found that the Young's moduli of the two elastic elements
      increased in cross-linked tissues and that cross-linking treatment therefore
      increased corneal rigidity. It is recognized that this observation is
      substantially in line with the conclusion reported in the literature, obtained
      using an exponential fitting function. It is observed, however, that the latter
      function implies a condition of non-zero stresses without strain, and does not
      provide interpretative insights for lack of any biomechanical basis. Above all,
      the function fits a singular trend, inexplicably claimed to be viscoelastic, with
      surprising perfection. In any case, using the reported data, the study
      demonstrates that a fitting equation obtained by a modelling approach not only
      shows the evident efficacy of the treatment, but also provides orientations for
      studying modifications induced in cross-linked fibres.

PMID- 19853405
TI  - [Digit purpura: an unreported sign of trichotillomania].

PMID- 19853406
TI  - [Thoughts about patient education: the experience of diabetes].
AB  - Patient education is not simply information or teaching or coaching. It is
      learning that is both practical and specialized, intended to help patients
      acquire therapeutic skills and to support them in changing their self-care
      practices to attain personalized objectives. It is therapeutic. An effective
      strategy to overcome health problems requires that patients not avoid the problem
      by denying the disease. Health prevention behavior requires that the patient be
      simultaneously confident in the prescribed treatments and able to project into
      the future. It is more difficult for asymptomatic patients to have a mental
      representation of the disease and thus be able to modify their lifestyle. Self
      measurement of blood glucose can create anxiety and make the risk of
      complications more tangible, but it is beneficial only if it induces action or
      reassurance. Changing behavior is possible only to the extent that it does not
      challenge the patient's own well-being. It may be unreasonable but it is also
      rational to refuse what the patient perceives as a threat to his or her own
      identity. Thus, physicians caring for patients with a chronic disease must be
      skilled in three different fields: biomedicine, pedagogy, and psychology.

PMID- 19853407
TI  - An item analysis of Raven's Colored Progressive Matrices among participants with
      Down syndrome.
AB  - Standardized tests are widely used in intellectual disability research, either as
      dependent or control variables. Yet, it is not certain that their items give rise
      to the same performance in various groups under study. In the present work, 48
      participants with Down syndrome were matched on their raw score on Raven's
      Colored Progressive Matrices (RCPM) with 48 participants with intellectual
      disability of undifferentiated etiology and 48 typical children. An item analysis
      was then conducted using the transformed item difficulties method, a statistical
      approach designed to detect differential item functioning between groups. Results
      showed that the difficulty of items was highly similar for the three groups. It
      is concluded that RCPM can be used with considerable confidence in comparative
      studies including typical, Down syndrome and intellectually disabled participants
      of undifferentiated etiology. Some methodological implications of these findings
      are discussed.

PMID- 19853409
TI  - Treatment of functional ventricular fold phonation by temporary suture
      lateralization.
AB  - Ventricular fold phonation (VFP) is a phenomenon characterized by phonation using
      the false vocal folds. Besides a substitution voice due to loss of the true vocal
      folds-so called compensatory type-the noncompensatory types have a psychogenic,
      functional, or habitual background. Therapeutic options for these cases so far
      comprise voice therapy, pharmacological therapy (injection of anesthetics or
      botulinum toxin), and, in case of failure, surgical resection of the ventricular
      folds. Indication for aggressive surgical interventions is usually difficult, as
      there is always a risk of producing an irreversible state with an even worse
      situation. We present two cases of functional (psychogenic) VFP treatment
      refractory to conservative treatment. Lateralization of the ventricular folds by
      an endo-extralaryngeal temporary suture, similar to that used in bilateral vocal
      fold paralysis, was performed. Immediately after the procedure, a constant
      phonation at glottic level could be achieved in both cases. Sutures were removed
      4 days after surgery, and phonation remained at the glottic level. Vocal fold
      phonation could be stabilized in the long run, and both patients recovered
      completely under additional voice therapy.

PMID- 19853408
TI  - Implantation of esterified hyaluronic acid in microdissected Reinke's space after
      vocal fold microsurgery: short- and long-term results.
AB  - In this study are reported the laryngeal and vocal results obtained after a
      microflap excision of benign vocal fold (VF) lesions and immediate implantation
      of esterified hyaluronic acid (EHA) in the surgical wound. In a previous pilot
      study on 11 cases, we have shown an excellent tolerance of this bioimplant. The
      objectives are to confirm the innocuity of the technique, to demonstrate the
      laryngeal and vocal evolution at short and long term, and to evaluate the
      eventual positive impact of EHA implantation on the pliability of the superficial
      layer of the lamina propria (SLLP) and on voice. This is a prospective and
      comparative study on 83 patients suffering from various benign VF lesions. Thirty
      three patients were implanted with EHA, whereas 50 patients did not undergo
      implantation at the end of the microsurgical procedure. All patients undergo
      rigid laryngoscopy and microflap excision procedure under general anesthesia.
      After freeing up of the Reinke's space and creation of a mucosal microflap, a few
      fibers of EHA are inserted in the surgical wound, before closure of the incision
      with fibrin glue. Serial laryngeal and vocal assessments are performed in all
      patients using videostroboscopy (Wolff and Xion), perceptual and objective voice
      evaluation (MDVP software, Kay Elemetrics), and phonatory function measurements
      (Aerophone II). Pre- and early postoperative means are compared by analysis of
      variance. Delayed and long-term evolution of laryngeal and vocal data are
      compared by means of nonparametric statistical methods. The longest follow-up in
      the implanted group is 4 years. Early postoperative results are similar in both
      groups: a significant improvement of a majority of laryngeal and vocal data is
      observed after microsurgery. In the long term, the two groups exhibit a different
      behavior: further improvement of voice, as an ongoing process, is only observed
      in the EHA implanted group, together with improvement of some videostroboscopic
      characteristics. The nonimplanted group remains stable, with no further
      improvement of the voice quality obtained after microsurgery. Excellent short-
      and long-term tolerance of EHA implantation is confirmed by this larger series.
      The use of EHA implant in microdissected SLLP is safe and leads to good laryngeal
      and vocal outcomes in the treated patients. More interestingly, treated cases
      exhibit a continuous improvement over a long period of time.

PMID- 19853410
TI  - Vocal fold nodules: morphological and immunohistochemical investigations.
AB  - The objective of this study was to investigate the morphological and
      immunohistochemical characteristics of vocal fold nodules. The study design was
      prospective and retrospective. For the histological study, we reviewed 15 slides
      from the surgical cases of vocal fold nodules, in which we analyzed epithelium,
      basal membrane (bm), and lamina propria. For the transmission and scanning
      electron microscopy (TEM, SEM) studies, five new cases on vocal fold nodules were
      included. Immunohistochemistry study was carried out in the 15 specimens, using
      antifibronectin, antilaminin, and anticollagen IV antibodies. The main
      histological alterations were epithelial hyperplasia (73.33%), basement membrane
      thickening (86.66%), edema, and fibrosis (93.33%). SEM--reduction in mucous
      lacing and increase in the desquamating cells, without epithelial erosion. TEM-
      hyperplasia of the epithelium, enlargement of the intercellular junctions, which
      was filled by fluid, subepithelial thickening of the lamina reticularis, and
      break points in the basal membrane. Immunohistochemistry--we identified greater
      immunoexpression of fibronectin on the basal membrane, on the lamina propria, and
      around the vessels. Antilaminin and anticollagen IV antibodies showed higher
      pigmentation on the endothelium of the vessels than that on the basal membrane.
      In vocal fold nodules, combined assessment using light microscopy, electron
      microscopy, and immunohistochemistry can reveal important morphological details
      useful in characterizing these lesions.

PMID- 19853411
TI  - Fourier cross-sectional profile for vessel detection on retinal images.
AB  - Retinal blood vessels are important objects in ophthalmologic images. In spite of
      many attempts for vessel detection, it appears that existing methodologies are
      based on edge detection or modeling of vessel cross-sectional profiles in
      intensity. The application of these methodologies is hampered by the presence of
      a wide range of retinal vessels. In this paper we define a universal
      representation for upward and downward vessel cross-sectional profiles with
      varying boundary sharpness. This expression is used to define a new scheme of
      vessel detection based on symmetry and asymmetry in the Fourier domain. Phase
      congruency is utilized for measuring symmetry and asymmetry so that our scheme is
      invariant to vessel brightness variations. We have performed experiments on
      fluorescein images and color fundus images to show the efficiency of the proposed
      algorithm technique. We also have performed a width measurement study, using an
      optimal medial axis skeletonization scheme as a post-processing step, to compare
      the technique with the generalized Gaussian profile modeling. The new algorithm
      technique is promising for automated vessel detection where optimizing profile
      models is difficult and preserving vessel width information is necessary.

PMID- 19853412
TI  - The clinical spectrum and immunobiology of parainfectious neuromyelitis optica
      (Devic) syndromes.
AB  - In a subgroup of patients with neuromyelitis optica (NMO), a severe inflammatory
      demyelinating disorder of autoimmune origin characterized by recurrent attacks of
      optic neuritis and longitudinally extensive transverse myelitis, a parainfectious
      pathogenesis may play a central role. We systematically evaluated such reports in
      the literature published between 1975 and 2009 in order to characterize
      parainfectious NMO syndromes. Identified were 25 cases, whereof 11 were in
      association with viral and 14 with bacterial pathogens. Sufficient clinical and
      paraclinical information was available in 16 patients (11 women). Median age was
      8 years for children and 32 years for adults. Acute febrile illness preceding or
      in close relation with neurological symptoms was most common and the association
      with varicella-zoster virus and Mycobacterium pneumonia most frequent. In the
      majority, the course was monophasic (88%) and disability sustained (with complete
      recovery in only 25%). Seven patients fulfilled the revised NMO diagnosis
      criteria of 2006; none was seropositve for aquaporin-4 antibodies. Immune
      mechanisms potentially involved in parainfectious NMO syndromes include bystander
      activation, molecular mimicry, and the exacerbation of a pre-existing central
      nervous system (CNS) disorder by a systemic infection. However, current studies
      are not sufficient to define the place of parainfectious NMO syndromes within the
      spectrum of inflammatory disorders of the CNS.

PMID- 19853413
TI  - Living skin equivalents constructed using human amnions as a matrix.
AB  - BACKGROUND: Living skin equivalents (LSEs) are being used to treat burn wounds,
      skin defects, and chronic wounds, and today, several biomaterials are applied as
      dermal matrices in LSEs. The amnionic membrane (AM) is known to have useful
      properties as a dermal matrix and can be used to construct a LSE. OBJECTIVE: To
      develop a new LSE with human AM as the matrix. METHODS: Human AM was de
      epithelialized and investigated to determine whether it supported keratinocyte
      adherence and proliferation, and fibroblast in-growth and proliferation. A new
      LSE was constructed by seeding keratinocytes on the epithelial side of fibroblast
      populated, de-epithelialized AM and was investigated histologically. The LSE was
      transplanted onto a full-thickness wound on a nude mouse and a histological
      examination was conducted. RESULTS: De-epithelialized AM supported the adherence
      and proliferation of keratinocytes and the in-growth of fibroblasts. The new LSE
      demonstrated good mechanical properties and revealed good morphology, with a well
      differentiated epidermis and well developed basement membrane. The LSE grafts
      survived well on nude mice, showing good morphology. CONCLUSION: A LSE with
      amnions as a matrix exhibited good morphology, low cost, and good mechanical
      properties and may be useful as a skin substitute for clinical use.

PMID- 19853414
TI  - White matter 'potholes' in early-onset schizophrenia: a new approach to evaluate
      white matter microstructure using diffusion tensor imaging.
AB  - There is considerable evidence implicating white matter abnormalities in the
      pathophysiology of schizophrenia. Many of the recent studies examining white
      matter have utilized diffusion tensor imaging (DTI) using either region of
      interest (ROI) or voxel-based approaches. Both voxel-based and ROI approaches are
      based on the assumption that the abnormalities in white matter overlap spatially.
      However, this is an assumption that has not been tested, and it is possible that
      aberrations in white matter occur in non-overlapping regions. In order to test
      for the presence of non-overlapping regions of aberrant white matter, we
      developed a novel image processing technique that evaluates for white matter
      'potholes,' referring to within-subject clusters of white matter voxels that show
      a significant reduction in fractional anisotropy. We applied this algorithm to a
      group of children and adolescents with schizophrenia compared to controls and
      found an increased number of 'potholes' in the patient group. These results
      suggest that voxel-based and ROI approaches may be missing some white matter
      differences that do not overlap spatially. This algorithm may be also be well
      suited to detect white matter abnormalities in disorders such as substance abuse,
      head trauma, or specific neurological conditions affecting white matter.

PMID- 19853415
TI  - Efficiency of working memory encoding in twins discordant for schizophrenia.
AB  - It has been proposed that patients with schizophrenia and some of their relatives
      suffer from reduced neurocognitive efficiency, increasing their sensitivity to
      experimental task demands. The present study evaluated such a possibility during
      performance of a working memory task by schizophrenia patients and their co-twins
      along with a healthy control sample. Electrophysiological data were obtained from
      sets of nine twin pairs (monozygotic and dizygotic pairs collapsed) discordant
      for a diagnosis of schizophrenia and from nine matched healthy control twin
      pairs, during administration of a variable-load spatial working memory task.
      Event-related potentials (ERPs) were measured immediately after memory set onset
      and during a delay period. For correctly performed trials, slow-wave ERP activity
      measured during the late stimulus encoding and delay periods exhibited a
      significant Diagnostic Group-by-Memory Load interaction, with schizophrenia
      patients showing a differentially strong load effect. Patients' co-twins
      displayed an intermediate level of load sensitivity while healthy controls showed
      no significant load effect. These results support an inefficiency model of
      neurocognitive dysfunction in schizophrenia, a pattern that appears to be related
      to the pathogenesis and inheritance of the disorder. Furthermore, this
      inefficiency appeared during the late stimulus encoding stage of working memory
      functioning, possibly reflecting disruptions in stimulus representation
      consolidation.

PMID- 19853416
TI  - Volumes of brain, grey and white matter and cerebrospinal fluid in schizophrenia
      in the Northern Finland 1966 Birth Cohort: an epidemiological approach to
      analysis.
AB  - Magnetic resonance imaging (MRI) studies in schizophrenia have seldom involved a
      general population birth cohort or other epidemiological samples. We studied the
      Northern Finland 1966 Birth Cohort and identified all people with psychotic
      disorders. Along with an unaffected age-matched control sample (n = 100) from the
      cohort, 54 subjects with schizophrenia underwent MRI brain scan at age 33-35
      years from which we defined volumes of whole brain, grey and white matter and
      intracranial cerebrospinal fluid (CSF). Whole brain, grey and white matter
      volumes were 2-3% smaller in the schizophrenia subjects, who showed a 7% increase
      in CSF volume. These volume changes were independent of the effects of gender,
      family history of psychosis, perinatal risks or age at onset of illness.
      Moreover, there was no evidence that the effects were due to particular subgroups
      of cases having very low or high values. Rather, there were linear trends in the
      associations between whole brain and grey matter volume measures and
      schizophrenia. Our study replicates the previous findings of brain volume
      differences in schizophrenia on a general population level.

PMID- 19853417
TI  - Midline and right frontal brain function as a physiologic biomarker of remission
      in major depression.
AB  - Prior investigations have reported that changes in the prefrontal
      electroencephalogram (EEG) precede symptom improvement from antidepressant
      medications, and could serve as a biomarker of treatment outcome in major
      depressive disorder (MDD). A new physiologically defined region of interest
      (ROI), overlying the midline and right frontal (MRF) cortical area, was examined
      here for a relationship between early decreases in theta-band cordance and
      remission. Subjects were 72 adults with unipolar MDD who had completed placebo
      controlled antidepressant treatment trials, with 37 randomized to medication and
      35 to placebo. We assessed changes in cordance and absolute and relative power in
      the MRF region at 48 h, 1 week, and 2 weeks after start of drug, as potential
      predictors of remission (final score on the 17-item Hamilton Depression Rating
      Scale of 5 or below. Out of 37 medication-treated subjects, 11 (30%) remitted
      versus 6 of 35 placebo subjects (17%). Change in MRF cordance 1 and 2 weeks after
      the beginning of treatment was significantly associated with remission in
      medication-treated subjects at 1 week, with receiver operating characteristic
      (ROC) analysis yielding 0.76 area under the curve. Decreases in MRF cordance at 1
      week predicted remission with medication with 69% overall accuracy (90%
      sensitivity; 60% specificity). MRF cordance changes were not associated with
      remission with placebo. Absolute and relative power did not differentiate groups.
      These results suggest that remission may be predictable from physiologic
      measurements after 1 week of treatment, and that this region merits further
      investigation in the neurobiology of treatment response.

PMID- 19853419
TI  - Complex methyl groups dynamics in [(CH3)4P]3Sb2Br9 (PBA) from low to high
      temperatures by proton spin-lattice relaxation and narrowing of proton NMR
      spectrum.
AB  - Molecular dynamics of a polycrystalline sample of [(CH(3))(4)P](3)Sb(2)Br(9)
      (PBA) has been studied on the basis of the T(1) (24.7 MHz) relaxation time
      measurement, the proton second moment of NMR and the earlier published T(1) (90
      MHz) relaxation times. The study was performed in a wide range of temperatures
      (30-337 K). The tunnel splitting omega(T) of the methyl groups was estimated as
      of low frequency (from kHz to few MHz). The proton spin pairs of the methyl group
      are known to perform a complex internal motion being a resultant of four
      components. Three of them involve mass transportation over and through the
      potential barrier and are characterized by the correlation times tau(3) and
      tau(T)of the jumps over the barrier and tunnel jumps in the threefold potential
      of the methyl group and tau(iso) the correlation time of isotropic rotation of
      the whole TMP cation. For tau(3) and tau(iso) the Arrhenius temperature
      dependence was assumed, while for tau(T)--the Schrodinger one. The fourth motion
      causes fluctuations of the tunnel splitting frequency, omega(T), and it is
      related to the lifetime of the methyl spin at the energy level. The correlation
      function for this fourth motion (tau(omega) correlation time) has been proposed
      by Muller-Warmuth et al. In this paper a formula for the correlation function and
      spectral density of the complex motion made of the above-mentioned four
      components was derived and used in interpretation of the T(1) relaxation time.
      The second moment of proton NMR line at temperatures below 50K is four times
      lower than its value for the rigid structure. The three components of the
      internal motion characterized by tau(T), tau(H), and tau(iso) were proved to
      reduce the second moment of the NMR line. The tunnel jumps of the methyl group
      reduce M(2) at almost 0K, the classical jumps over the barrier reduce M(2) in the
      vicinity of 50K, while the isotropic motion near 150K. Results of the study on
      the dynamics of CH(3) groups of TMP cation based on the second moment
      measurements were correlated with those based on T(1) time measurements.

PMID- 19853418
TI  - A voxel-based morphometry comparison of regional gray matter between fragile X
      syndrome and autism.
AB  - The phenotypic association between fragile X syndrome (FXS) and autism is well
      established, but no studies have directly compared whole-brain anatomy between
      the two disorders. We performed voxel-based morphometry analyses of magnetic
      resonance imaging (MRI) scans on 10 individuals with FXS, 10 individuals with
      autism, and 10 healthy comparison subjects to identify volumetric changes in each
      disorder. Regional gray matter volumes within frontal, parietal, temporal, and
      cingulate gyri, as well as in the caudate nuclei and cerebellum, were larger in
      the FXS group relative to the autism group. In addition, volume increases in FXS
      were observed in frontal gyri and caudate nuclei compared to controls. The autism
      group exhibited volume increases in frontal and temporal gyri relative to the FXS
      group, and no volume increases relative to controls. Volumetric deficits relative
      to controls were observed in regions of the cerebellum for both groups, with
      additional deficits in parietal and temporal gyri for the FXS group. Our caudate
      nuclei and frontal gyri results may implicate dysfunction of frontostriatal
      circuitry in FXS. Cerebellar deficits suggest atypical development of the
      cerebellum contributing to the phenotype of both disorders, but further imply
      that unique cerebellar regions contribute to the phenotype of each disorder.

PMID- 19853420
TI  - Ammonium methacrylate units polymer content and their effect on acyclovir
      colloidal nanoparticles properties and bioavailability in human volunteers.
AB  - Acyclovir (ACV)-Eudragit (EUD) nanoparticles (NPs) were prepared using both EUD
      RS 100 and RL 100 with different charge density. The effect of charge intensity
      on particle size, encapsulation efficiency, and in vitro dissolution was
      assessed. The bioavailability of ACV NP colloids were evaluated in human
      volunteers, compared with commercial product using a validated LC-MS/MS method
      with a lower limit of quantification (LLOQ) of 0.02 microg/ml. EUD RL 100 with
      higher ammonium groups gave smaller NPs than EUD RS 100. The surface charge of
      the polymer did not affect encapsulation efficiency and in vitro dissolution. In
      human volunteers, both F2 and F5 colloidal nanosuspensions prepared with EUD RS
      and RL respectively in drug to polymer ratio 1:3 sustained the oral absorption of
      ACV, expressed by the significant lower C(max), significant delayed T(max) and
      the significant higher HVD(t 50%C(max)). The mean C(max) of F2, F5, and Zovirax
      were 0.61+/-0.06, 0.73+/-0.07 and 0.92+/-0.21 microg/ml respectively.
      Furthermore, the AUC(0-12) of F2 and F5 was significantly higher than that of
      Zovirax((R)) with values of 4.37+/-0.88, 5.14+/-0.87 and 3.21+/-0.53 microg/ml h
      respectively. The higher AUC(0-12) for both F2 and F5 reflected high relative
      bioavailability of 136.2% and 159.9% respectively compared to commercial ACV
      tablets.

PMID- 19853421
TI  - Hyaluronidase binds differently DPPC, DPPS or GlcNAc-bearing glycolipid
      biomimetic monolayers.
AB  - Bovine testis hyaluronidase (btHyal) had been shown to have direct effects on
      cancer cells and to be a useful adjuvant in several medicines. Furthermore this
      enzyme had been found to be membrane-associated. Thus, in this work, the
      interactions between btHyal and membranes were analyzed by using lipid monolayers
      at the air-water interface as a biomimetic membrane system. This allowed us to
      define the btHyal interactions with two residues of hyaluronic acid (a btHyal
      substrate), GlcNAc and carboxylic group, which are present in cholesteryl
      triethoxy-N-acetylglucosamine (Chol-E3-GlcNAc) and in DPPS, respectively. btHyal
      bound preferentially Chol-E3-GlcNAc monolayers and showed a decreasing affinity
      for Chol-E3-GlcNAc-DPPC monolayers containing decreasing amount of glycolipid,
      suggesting a crucial role of the glycolipid GlcNAc. Furthermore the significant
      btHyal binding to DPPS was not affected by the presence of free GlcNAc in the
      subphase. These results and the absence of significant binding of btHyal to pure
      DPPC monolayer suggest that the protein interacts with the lipid monolayer by
      mimicking the enzyme-substrate interactions or by electrostatic interactions.

PMID- 19853422
TI  - S-layer templated bioinspired synthesis of silica.
AB  - The current understanding of the molecular mechanisms involved in the bioinspired
      formation of silica structures laid foundation for investigating the potential of
      the S-layer protein SbpA from Lysinibacillus sphaericus CCM 2177 as catalyst,
      template and scaffold for the generation of novel silica architectures. SbpA
      reassembles into monomolecular lattices with square (p4) lattice symmetry and a
      lattice constant of 13.1 nm. Silica layers on the S-layer lattice were formed
      using tetramethoxysilane (TMOS) and visualized by transmission electron
      microscopy. In situ quartz crystal microbalance with dissipation monitoring (QCM
      D) measurements showed the adsorption of silica in dependence on the presence of
      phosphate in the silicate solution and on the preceding chemical modification of
      the S-layer. An increased amount of precipitated silica could be observed when
      K2HPO4/KH2PO4 was present in the solution (pH 7.2). Further on, independent of
      the presence of phosphate the silica deposition was higher on S-layer lattices
      upon activation of their carboxyl groups with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide hydrochloride (EDC) compared to native S-layers
      or EDC treated S-layers when the activated carboxyl groups were blocked with
      ethylene diamine (EDA). Fourier transform infrared attenuated total reflectance
      (FTIR-ATR) spectroscopy revealed the formation of an amorphous silica gel
      (SiO2)x.yH2O on the S-layer. The silica surface concentrations on the S-layer was
      4 x 10(-9) to 2 x 10(-8) mol cm(-2) depending on the modification of the protein
      layer and corresponded to 4-21 monolayers of SiO2.

PMID- 19853423
TI  - PLGA particle production for water-soluble drug encapsulation: degradation and
      release behaviour.
AB  - Particles for subcutaneous depot use encapsulating a model water-soluble drug
      have been produced from poly(lactic-glycolic acid) (PLGA) using a membrane
      emulsification-solvent evaporation technique. The release behaviour, mainly the
      change in size and inner morphology are reported. During release, the particles
      initially swelled in size, then reduced. A diffusion based model, taking in to
      account the change in particle size, is presented. Surface erosion is evident
      from the particle size and image evidence, and the diffusion model provides a fit
      to the data even during the surface erosion period, suggesting that the model
      drug diffuses before the particle degrades.

PMID- 19853424
TI  - [Drugs news].

PMID- 19853425
TI  - Bacterial community in the East Rongbuk Glacier, Mt. Qomolangma (Everest) by
      culture and culture-independent methods.
AB  - The abundance of total and culturable bacteria deposited into the East Rongbuk
      ice core was investigated, and the bacterial content was examined through culture
      and culture-independent approaches. Total counts of bacteria in the ice core
      ranged from 0.02 x 10(3) to 6.4 x 10(3) cells ml(-1). Viable bacteria varied
      between 0 and 5.6 CFU ml(-1) on PYGV and R2A media. The phylogenetic trees placed
      the culturable bacteria into four major groups: Actinobacteria, Firmicutes,
      Proteobacteria and Deinococcus-Thermus, with Firmicutes being the most prevalent.
      They exhibited unique phenotypic properties with large and non-pigmented cells.
      The diversity revealed by H' index of DGGE analysis was 0-0.75, and closer
      sections showed higher similarity of bacterial DNA structure. Members of two
      major lineages were found: Firmicutes and Proteobacteria. The combined culture
      and culture-independent methods indicated layer distribution of bacterial
      community in the ice core section, which might reflect the ecological
      environments on glacier at time of their deposition.

PMID- 19853426
TI  - Purification and characterization of a novel glucansucrase from Leuconostoc
      lactis EG001.
AB  - A gene encoding glucansucrase was identified in Leuconostoc lactis EG001 isolated
      from lactic acid bacteria (LAB) in Kimchi, a traditional Korean fermented food.
      The L. lactis EG001 glucansucrase gene consists of 4503 bp open reading frame
      (ORF) and encodes an enzyme of 1500 amino acids with an apparent molecular mass
      of 165 kDa. The deduced amino-acid sequence showed the highest amino-acid
      sequence identity (75%) to that of dextransucrase of L. mesenteroides. The gene
      was cloned and over-expressed in Escherichia coli strain. The recombinant enzyme
      was purified via Ni-NTA affinity chromatography and its enzymatic properties were
      characterized. The enzyme exhibited optimum activity at 30 degrees C and pH 5.0.
      In addition, the enzyme was able to catalyze the glycosylation of l-ascorbic acid
      to l-ascorbic acid 2-glucoside. The glycosylated product via EG001 glucansucrase
      has the potential as an antioxidant in industrial applications.

PMID- 19853427
TI  - A chimeric laccase with hybrid properties of the parental Lentinula edodes
      laccases.
AB  - We created a chimeric laccase from two different laccases, Lcc1 and Lcc4, from
      Lentinula edodes. Lcc1 is a secretory lignin-degrading enzyme produced in liquid
      cultures of L. edodes. Lcc4 is a tissue-accumulating-type enzyme, which is
      thought to be involved in melanin synthesis in fruiting body after harvesting.
      Lcc1 and Lcc4 differ in their Km values for some substrates, especially beta-(3,4
      dihydroxyphenyl) alanine (L-DOPA) and catechol. The novel chimeric laccase,
      Lcc4/1, has properties that are a hybrid of those of Lcc1 and Lcc4. Lcc4/1 acts
      upon both Lcc1 and Lcc4 substrates and most of its Km values are lower than those
      of Lcc1 and Lcc4. Homology modeling indicates that the deduced shape of the
      substrate-binding pocket of the chimeric laccase is larger than that of Lcc1 and
      similar to that of Lcc4. The other biochemical properties, such as temperature
      and pH dependency, are intermediate between those of Lcc1 and Lcc4.

PMID- 19853428
TI  - Experimental evidences of pSym transfer in a native peanut-associated rhizobia.
AB  - In previous works we have characterized the native bacterial diversity associated
      with root nodules of peanut grown in Cordoba province, Argentina. Studies
      performed in the isolate Rhizobium sp. NET30 revealed a phylogenetic incongruence
      between housekeeping and nodulation genes. This discrepancy could be explained by
      the horizontal transfer of nodulation genes from the native peanut isolate
      Rhizobium sp. NCHA22, a bacterium that showed high identity percentages with
      Rhizobium tropici IIB strains in the basic and symbiotic genes analyzed. In this
      work, we demonstrate that, in R. sp. NCHA22, genes required for nodule formation
      in common bean (Phaseolus vulgaris L.) are plasmid-borne. A symbiotic plasmid
      capable of conjugal transfer to different genetic backgrounds was identified in
      this isolate. The mechanism involved in the plasmidic transfer differs from that
      described for R. tropici CIAT899 (R. tropici IIB type strain). The transfer of a
      symbiotic plasmid, and the subsequent homologous recombination of nodulation
      genes in R. sp. NET30 genetic background could account for the phylogenetic
      incongruence determined in this isolate. Results are also indicating that the
      transfer of the R. tropici NCHA22 pSym may be a frequent event in native
      conditions.

PMID- 19853430
TI  - Material and energy recovery from Automotive Shredded Residues (ASR) via
      sequential gasification and combustion.
AB  - Shredding is the common end-of-life treatment in Europe for dismantled car
      wrecks. It produces the so-called Automotive Shredded Residue (ASR), usually
      disposed of in landfill. This paper summarizes the outcome of a study carried out
      by Politecnico di Milano and LEAP with the support of Actelios SpA on the
      prospects of a technology based on sequential gasification and combustion of this
      specific waste stream. Its application to the treatment of ASR allows the
      recovery of large fractions of metals as non-oxidized, easily marketable
      secondary raw materials, the vitrification of most of the ash content and the
      production of power via a steam cycle. Results show that despite the unfavourable
      characteristics of ASR, the proposed technology can reach appealing energy
      performances. Three of four environmental impact indicators and the cumulative
      energy demand index are favourable, the main positive contributes being
      electricity production and metal recovery (mainly aluminium and copper). The only
      unfavourable indicator is the global warming index because, since most of the
      carbon in ASR comes from fossil sources, the carbon dioxide emissions at the
      stack of the thermal treatment plant are mainly non-renewable and, at the same
      time, the avoided biogas production from the alternative disposal route of
      landfilling is minor.

PMID- 19853431
TI  - Combining stakeholder analysis and spatial multicriteria evaluation to select and
      rank inert landfill sites.
AB  - This paper presents a method based on the combination of stakeholder analysis and
      spatial multicriteria evaluation (SMCE) to first design possible sites for an
      inert landfill, and then rank them according to their suitability. The method was
      tested for the siting of an inert landfill in the Sarca's Plain, located in south
      western Trentino, an alpine region in northern Italy. Firstly, stakeholder
      analysis was conducted to identify a set of criteria to be satisfied by new inert
      landfill sites. SMCE techniques were then applied to combine the criteria, and
      obtain a suitability map of the study region. Subsequently, the most suitable
      sites were extracted by taking into account also thresholds based on size and
      shape. These sites were then compared and ranked according to their visibility,
      accessibility and dust pollution. All these criteria were assessed through GIS
      modelling. Sensitivity analyses were performed on the results to assess the
      stability of the ranking with respect to variations in the input (criterion
      scores and weights). The study concluded that the three top-ranking sites are
      located close to each other, in the northernmost sector of the study area. A more
      general finding was that the use of different criteria in the different stages of
      the analysis allowed to better differentiate the suitability of the potential
      landfill sites.

PMID- 19853429
TI  - Anti-inflammatory and pro-resolving properties of benzo-lipoxin A(4) analogs.
AB  - Lipoxins (LXs) are potent endogenous counter-regulatory lipid mediators that
      dampen acute inflammation and promote its resolution. Here, we present our
      investigation of a new class of thermally and metabolically stable benzo-LXA(4)
      analogs that are potently anti-inflammatory and easier to synthesize. Replacement
      of the tetraene unit of native LXA(4) with a benzo-fused ring system not only
      increases the thermal stability but also enables highly convergent and efficient
      syntheses of these analogs. In addition, they resist rapid catalysis and
      inactivation by eicosanoid oxidoreductase. Like native LXs, o-[9, 12]-benzo
      omega6-epi-LXA(4), o-[9, 12]-benzo-deoxy-LXA(4), m-[9, 12]-benzo-omega6-epi
      LXA(4) and [9, 14]-benzo-omega6-(R/S)-LXA(4) demonstrated potent time-dependent
      reduction, at nanogram dosages, of PMN infiltration and pro-inflammatory cytokine
      generation in vivo in murine peritonitis and were organ protective in hind limb
      ischemia-reperfusion injury of the lung. The o-[9, 12]-benzo-omega6-epi-LXA(4)
      and m-[9, 12]-benzo-omega6-epi-LXA(4) were most potent in nanogram doses; both
      decreased PMN infiltration by approximately 32%, while o-[9, 12]-benzo-deoxy
      LXA(4) and [9, 15]-omega6-(R/S)-LXA(4) were less potent. The [9,12]-benzo-omega6
      epi-LXA(4) also activated a lipoxin A(4) GPCR and increased macrophage phagocytic
      activity. Taken together, these findings demonstrate a new generation of LXA(4)
      stable analogs that are easy to synthesize and anti-inflammatory. These benzo
      LXA(4) analogs are promising tools for new therapeutic approaches as well as
      assessing endogenous mechanisms in anti-inflammation and resolution.

PMID- 19853432
TI  - The influence of artificial sealing on the capillary barrier's function.
AB  - Regulations for the sealing of landfill sites require two independent sealing
      components. To satisfy this requirement, the combined capillary barrier was
      developed using impermeable sheeting placed between the capillary layer and the
      capillary block of the traditional capillary barrier. In this study, a numerical
      model is introduced based on hydraulic characteristics obtained by means of
      measurements of samples of capillary barrier materials. To make a comparison
      possible, samples of a laboratory investigated barrier were measured. Two
      laboratory experiments with a simple and a combined capillary barrier were
      repeated using the developed numerical model and good agreement between computed
      and measured results was found. Subsequently, the model was used for
      investigating the effect of failure of the artificial sheeting on the capillary
      barrier's efficiency. The obtained results are presented and discussed.

PMID- 19853433
TI  - An investigation on the use of shredded waste PET bottles as aggregate in
      lightweight concrete.
AB  - In this work, the utilization of shredded waste Poly-ethylene Terephthalate (PET)
      bottle granules as a lightweight aggregate in mortar was investigated.
      Investigation was carried out on two groups of mortar samples, one made with only
      PET aggregates and, second made with PET and sand aggregates together.
      Additionally, blast-furnace slag was also used as the replacement of cement on
      mass basis at the replacement ratio of 50% to reduce the amount of cement used
      and provide savings. The water-binder (w/b) ratio and PET-binder (PET/b) ratio
      used in the mixtures were 0.45 and 0.50, respectively. The size of shredded PET
      granules used in the preparation of mortar mixtures were between 0 and 4 mm. The
      results of the laboratory study and testing carried out showed that mortar
      containing only PET aggregate, mortar containing PET and sand aggregate, and
      mortars modified with slag as cement replacement can be drop into structural
      lightweight concrete category in terms of unit weight and strength properties.
      Therefore, it was concluded that there is a potential for the use of shredded
      waste PET granules as aggregate in the production of structural lightweight
      concrete. The use of shredded waste PET granules due to its low unit weight
      reduces the unit weight of concrete which results in a reduction in the death
      weight of a structural concrete member of a building. Reduction in the death
      weight of a building will help to reduce the seismic risk of the building since
      the earthquake forces linearly dependent on the dead-weight. Furthermore, it was
      also concluded that the use of industrial wastes such as PET granules and blast
      furnace slag in concrete provides some advantages, i.e., reduction in the use of
      natural resources, disposal of wastes, prevention of environmental pollution, and
      energy saving.

PMID- 19853434
TI  - Low-reactive circulating fluidized bed combustion (CFBC) fly ashes as source
      material for geopolymer synthesis.
AB  - In this contribution, low-reactive circulating fluidized bed combustion (CFBC)
      fly ashes (CFAs) have firstly been utilized as a source material for geopolymer
      synthesis. An alkali fusion process was employed to promote the dissolution of Si
      and Al species from the CFAs, and thus to enhance the reactivity of the ashes. A
      high-reactive metakaolin (MK) was also used to consume the excess alkali needed
      for the fusion. Reactivities of the CFAs and MK were examined by a series of
      dissolution tests in sodium hydroxide solutions. Geopolymer samples were prepared
      by alkali activation of the source materials using a sodium silicate solution as
      the activator. The synthesized products were characterized by mechanical testing,
      scanning electron microscopy (SEM), X-ray diffractography (XRD), as well as
      Fourier transform infrared spectroscopy (FTIR). The results of this study
      indicate that, via enhancing the reactivity by alkali fusion and balancing the
      Na/Al ratio by additional aluminosilicate source, low-reactive CFAs could also be
      recycled as an alternative source material for geopolymer production.

PMID- 19853435
TI  - A biosensor based on photonic crystal surface waves with an independent
      registration of the liquid refractive index.
AB  - A high-precision optical biosensor technique capable of independently determining
      the refractive index (RI) of liquids is presented. Photonic crystal surface waves
      were used to detect surface binding events, while an independent registration of
      the critical angle was used for accurate determination of the liquid RI. This
      technique was tested using binding of biotin molecules to a streptavidin
      monolayer at low and high biotin concentrations. The attained baseline noise is
      5x10(-13) m/Hz(1/2) for adlayer thickness changes and 9x10(-8) RIU/Hz(1/2) for RI
      changes.

PMID- 19853436
TI  - Ultrasensitive chemiluminescence quantification of single-nucleotide
      polymorphisms by using monobase-modified Au and CuS nanoparticles.
AB  - An ultrasensitive chemiluminescence method based on the Au nanoparticles
      amplification for the quantitative detection of single-nucleotide polymorphisms
      (SNPs) in genomic DNA was accomplished by the DNA polymerase I (Klenow fragment)
      induced coupling of the nucleotide-modified nanoparticle probe to the mutant
      sites of duplex DNA under the Watson-Crick base-pairing rule. The concentration
      of the one-base mutant DNA was determined by chemiluminescence (CL) detection of
      the cupric ions dissolved from the CuS nanoparticles (NPs) modified on the Au
      NPs. The incorporation of Au NPs in this method significantly enhanced the
      sensitivity because a single Au NP can be loaded with 77 CuS NPs through the link
      age of an amidization reaction between mercaptoacetic acid on the surface of Au
      NPs and aminoethanethiol on the surface of CuS NPs. A preconcentration process of
      cupric ions performed by anodic stripping voltammetric (ASV) technology further
      increased the sensitivity of the design for about 10-fold. As a result of these
      two combined effects, this method could detect as low as 19 aM SNPs and the
      linear range for SNPs was from 8.0x10(-17) to 1.0x10(-14) M.

PMID- 19853437
TI  - Prognostic and predictive factors for outcome to first-line ifosfamide-containing
      chemotherapy for adult patients with advanced soft tissue sarcomas: an
      exploratory, retrospective analysis on large series from the European
      Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma
      Group (EORTC-STBSG).
AB  - BACKGROUND: Adult patients with advanced soft tissue sarcomas (STS) are generally
      treated similarly, regardless of great differences between STS subtypes, disease
      presentation and patients' characteristics. As ifosfamide is frequently applied
      in first line systemic therapy, we aimed to establish prognostic and predictive
      factors for outcome to ifosfamide-based therapy. METHODS: A retrospective,
      exploratory analysis was performed on data from 1337 advanced STS patients who
      received first-line ifosfamide-containing chemotherapy. For predictive factor
      analysis, 660 patients treated with doxorubicin monotherapy served as
      comparators. RESULTS: Independent favourable prognostic factors for overall
      survival (OS) were good performance status, female gender, low histological
      grade, extremity primary tumour site and locally advanced disease; for
      progression-free survival (PFS), the combination of doxorubicin and ifosfamide,
      locally advanced disease, and tumour entity with a lower risk to progress for
      synovial sarcoma patients compared to leiomyosarcoma. For response, independent
      favourable prognostic factors were doxorubicin combined with ifosfamide, higher
      histological grade, and histology with synovial sarcoma patients having the
      highest chance to respond. Predictive factor analysis showed that compared to
      doxorubicin monotherapy, patients who benefited less from ifosfamide-based
      therapies were leiomyosarcoma patients in terms of OS, and patients with
      liposarcoma for response. No predictive factors were found for PFS. CONCLUSION:
      In this study, we established an independent set of prognostic and predictive
      factors for outcome to ifosfamide-based chemotherapy in advanced STS patients.
      This study provides important information for the interpretation and design of
      clinical trials for specific STS entities and may contribute to further treatment
      individualisation of advanced STS patients.

PMID- 19853439
TI  - Novel biphenylcarboxylic acid peroxisome proliferator-activated receptor (PPAR)
      delta selective antagonists.
AB  - We designed and synthesized novel PPARdelta antagonists based on the crystal
      structure of the PPARdelta full agonist TIPP-204 bound to the PPARdelta ligand
      binding domain, in combination with our nuclear receptor helix 12 folding
      modification hypothesis. Representative compound 3a exhibits PPARdelta
      preferential antagonistic activity.

PMID- 19853438
TI  - A case of ectopic breast cancer with a literature review.
AB  - A 63-year-old woman was referred to our hospital because of a right axillary
      nodule in 2004. Physical examination showed a spherical nodule measuring 0.5cm in
      diameter in the right axilla. No mass was palpable in either breast. Mammograms
      were normal. Ultrasonography revealed a subcutaneous hypoechoic mass 0.7mm in
      maximum diameter in the right axilla. The patient underwent an excisional biopsy.
      Histological examination revealed an invasive ductal carcinoma (scirrhous
      carcinoma) in ectopic breast tissue. The patient subsequently underwent a wide
      local excision of the tissue surrounding the biopsy scar, with axillary lymph
      node dissection. Histologically, no residual tumor or nodal metastasis was found.
      Postoperatively, she received endocrine therapy and remains well, without any
      evidence of recurrence 4 years 10 months after operation. Cancer of the ectopic
      breast tissue is rare, and most cases present as a solitary axillary mass. Long
      term outcomes remain unclear. We present a case of breast carcinoma in the
      axillary ectopic mammary gland and summarize the clinical features of 94 cases,
      including ours, in Japan. We also compare long-term survival between ectopic
      breast cancer and usual breast cancer according to TNM T stage and lymph node
      metastasis.

PMID- 19853440
TI  - Anti-HBV agents. Part 3: preliminary structure-activity relationships of tetra
      acylalisol A derivatives as potent hepatitis B virus inhibitors.
AB  - Thirty-two tetra-acylated derivatives of alisol A were synthesized and evaluated
      for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro.
      Among the series of alisol A derivatives examined, five analogues were active
      against HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion in HepG
      2.2.15 cells. These results also provide interesting structure-activity
      relationships of tetra-acylalisol A derivatives. Compounds tetra-acetyl alisol A
      (A1), tetra-methoxyacetyl alisol A (A23), and tetra-ethoxyacetyl alisol A (A24)
      exhibited high activities against secretion of HBsAg with IC(50) values of
      0.0048, 0.0044, and 0.014 mM, respectively, HBeAg with IC(50) values of 0.011,
      0.012, and 0.018 mM, respectively, and remarkable selective index values
      SI(HBsAg)>333, SI(HBeAg)>145; SI(HBsAg)=209, SI(HBeAg)=77; and SI(HBsAg)>200,
      SI(HBeAg)>156, respectively. Additional studies in rats showed that compound A1
      has favorable pharmacokinetic prosperities for further development purpose, with
      elimination half-time (t(1/2)) of 1.63 h and oral bioavailability (F) of 40.9%.

PMID- 19853441
TI  - Synthesis and evaluation of D-gluco-pyranocyclopropyl amines as potential
      glucosidase inhibitors.
AB  - In the recent past sugar-derived cyclopropylamines were proposed as structurally
      new glycosidase inhibitors. In this Letter we report our efforts in the synthesis
      of a set of alpha-glucose configured oxabicyclo[4.1.0] heptanes, based on this
      hypothesis, bearing an amine substituent on the propyl ring and reveal that their
      inhibitory potential towards a range of mammalian glucosidases is modest.

PMID- 19853442
TI  - New classes of potent and bioavailable human renin inhibitors.
AB  - New classes of de novo designed renin inhibitors are reported. Some of these
      compounds display excellent in vitro and in vivo activities toward human renin in
      a TGR model. The synthesis of these new types of mono- and bicyclic scaffolds are
      reported, and properties of selected compounds discussed.

PMID- 19853443
TI  - (4-Piperidinyl)-piperazine: a new platform for acetyl-CoA carboxylase inhibitors.
AB  - Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid
      synthesis, play important roles in modulating energy metabolism. The inhibition
      of ACC has demonstrated promising therapeutic potential for treating obesity and
      type 2 diabetes mellitus in transgenic mice and preclinical animal models. We
      describe herein the synthesis and structure-activity relationships of a series of
      disubstituted (4-piperidinyl)-piperazine derivatives as a new platform for ACC1/2
      non-selective inhibitors.

PMID- 19853444
TI  - Novel Twinkle gene mutation in autosomal dominant progressive external
      ophthalmoplegia and multisystem failure.
AB  - A Saudi Arabian family presented with adult onset autosomal dominant progressive
      external ophthalmoplegia (adPEO) complicated by late onset reversible failure of
      the CNS, respiratory, hepatic, and endocrine systems. Clinical findings were
      suggestive of mitochondrial dysfunction and multiple mitochondrial DNA deletions
      were demonstrated on long range and real time polymerase chain reaction assays
      but not on Southern blotting. The disorder is caused by a novel heterozygous PEO1
      mutation predicting a Leu360Gly substitution in the twinkle protein. The peculiar
      clinical presentation expands the variable phenotype observed in adPEO and
      Twinkle gene mutations.

PMID- 19853445
TI  - Neuromuscular disease presentation with three genetic defects involving two
      genomes.
AB  - An extensive range of molecular defects have been identified in the human
      mitochondrial genome (mtDNA), many associated with well-characterised,
      progressive neurological syndromes. We describe a patient who presented to a
      mitochondrial clinic with progressive bilateral ptosis, external opthalmoplegia
      and increasing difficulty with walking. He had previously been diagnosed with a
      dominant, demyelinating polyneuropathy due to PMP22 gene duplication and had also
      developed gout, presenting in acute renal failure, due to an X-linked recessive
      HPRT gene mutation. Muscle biopsy revealed many COX-deficient fibres which we
      show contain high levels of a third genetic defect--a novel, mitochondrial
      tRNA(Leu(CUN)) (MTTL2) gene mutation.

PMID- 19853446
TI  - Late-onset MNGIE without peripheral neuropathy due to incomplete loss of
      thymidine phosphorylase activity.
AB  - Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE) is an autosomal
      recessive disorder characterized by severe gastrointestinal dysmotility,
      cachexia, peripheral neuropathy, ptosis, ophthalmoplegia, and leukoencephalopathy
      with early onset and severe prognosis. Mutations in the TYMP/ECGF1 gene cause a
      loss of thymidine phosphorylase catalytic activity, disrupting the homeostasis of
      intramitochondrial nucleotide pool. We report a woman with a very late onset of
      MNGIE, lacking peripheral neuropathy. Thymidine phosphorylase activity was
      markedly reduced in cultured fibroblasts, but only mildly reduced in buffy coat,
      where the defect is usually detected, and plasma thymidine was mildly increased
      compared to typical MNGIE patients. TYMP/ECGF1 analysis detected two heterozygous
      mutations, including a novel missense mutation. These findings indicate that a
      partial loss of thymidine phosphorylase activity may induce a late-onset and
      incomplete MNGIE phenotype.

PMID- 19853447
TI  - Wild chimpanzees rely on cultural knowledge to solve an experimental honey
      acquisition task.
AB  - Population and group-specific behavioral differences have been taken as evidence
      for animal cultures, a notion that remains controversial. Skeptics argue that
      ecological or genetic factors, rather than social learning, provide a more
      parsimonious explanation. Work with captive chimpanzees has addressed this
      criticism by showing that experimentally created traditions can be transmitted
      through social learning. Recent fieldwork further suggests that ecological and
      genetic factors are insufficient to explain the behavioral differences seen
      between communities, but the data are only observational. Here, we present the
      results of a field experiment that compared the performance of chimpanzees (P. t.
      schweinfurthii) from two Ugandan communities, Kanyawara and Sonso, on an
      identical task in the physical domain-extracting honey from holes drilled into
      horizontal logs. Kanyawara chimpanzees, who occasionally use sticks to acquire
      honey, spontaneously manufactured sticks to extract the experimentally provided
      honey. In contrast, Sonso chimpanzees, who possess a considerable leaf technology
      but no food-related stick use, relied on their fingers, but some also produced
      leaf sponges to access the honey. Our results indicate that, when genetic and
      environmental factors are controlled, wild chimpanzees rely on their cultural
      knowledge to solve a novel task.

PMID- 19853448
TI  - Testing for direct and indirect effects of mate choice by manipulating female
      choosiness.
AB  - Despite a massive research effort, our understanding of the evolution of female
      mate choice remains incomplete [1, 2]. A central problem is that the
      predominating empirical research tradition has focused on male traits, yet the
      key question is whether female choice traits are maintained because of direct
      effects on female fitness or because of indirect genetic effects in offspring
      that may be associated with such traits. Here, we address this question by using
      a novel research strategy that employs experimental phenotypic manipulation of a
      female choice trait in an insect model system, the seed beetle Callosobruchus
      chinensis (Coleoptera: Bruchidae). We show that females with increased efficiency
      of choice enjoy strongly elevated fitness compared to females with reduced choice
      efficiency. In contrast, we found no effects of female choice efficiency on
      offspring fitness. Our results show that female choice is maintained by direct
      selection in females in this system, whereas indirect selection is relatively
      weak at most. We suggest that phenotypic engineering of female choice traits can
      greatly advance our ability to elucidate the relative importance of direct and
      indirect selection for the maintenance of female choice.

PMID- 19853449
TI  - Oriented cell division as a response to cell death and cell competition.
AB  - The imaginal disc epithelia that give rise to the adult ectoderm of Drosophila
      can compensate to produce normal adult organs after damage. We looked at the
      local response to cell death by using two genetic methods to elevate cell death
      rates. During cell competition, sporadic cell death occurs predictably along the
      boundaries between populations of competing wild-type and "Minute" cells (M/+).
      Boundaries between M/+ and wild-type populations show an unusual degree of
      mixing, associated with mitotic reorientation of wild-type cells toward M/+
      territory that they take over. Apoptosis of M/+ cells was the cue, and reoriented
      mitosis required the planar cell polarity genes dachsous, fat, and atrophin.
      Clones mutated for pineapple eye, an essential gene, elevate apoptosis by a
      noncompetitive mechanism. Mitosis was also reoriented near cells mutant for
      pineapple eye, likewise dependent on the planar cell polarity genes. These
      findings show that planar cell polarity genes are required for responses to cell
      death. Oriented mitosis may help maintain morphology as dividing cells replace
      those that have been lost.

PMID- 19853450
TI  - Crowding in peripheral vision: why bigger is better.
AB  - We enjoy the illusion that visual resolution is high across the entire field of
      vision. However, this illusion can be easily dispelled by trying to identify
      objects in a cluttered environment out of the corner of your eye. This reflects,
      in part, the well-known decline in visual resolution in peripheral vision;
      however, the main bottleneck for reading or object recognition in peripheral
      vision is crowding. Objects that can be easily identified in isolation seem
      indistinct and jumbled in clutter. Crowding is thought to reflect inappropriate
      integration of the target and flankers in peripheral vision [1, 2]. Here, we
      uncover and explain a paradox in peripheral crowding: under certain conditions,
      increasing the size or number of flanking rings results in a paradoxical decrease
      in the magnitude of crowding-i.e., the bigger or more numerous the flanks, the
      smaller the crowding. These surprising results are predicted by a model in which
      crowding is determined by the centroids of approximately 4-8 independent features
      within approximately 0.5x the target eccentricity. These features are then
      integrated into a texture beyond the stage of feature analysis. We speculate that
      this process may contribute to the illusion of high resolution across the field
      of vision.

PMID- 19853452
TI  - A reflection from the other side of the bed--an account of what it is like to be
      a patient and a relative in an intensive care unit.
AB  - Following a two-day history of pyrexia, stomach pain, diarrhoea and an emergency
      laparotomy my wife was admitted to an intensive care unit (ICU) with septic
      shock. Lucy was artificially ventilated for seven days, and was treated with
      fluids, vasopressors and antibiotics. Her condition continued to deteriorate and
      on about the third day she looked as though she might die. However over the next
      few days Lucy began to recover and she was eventually transferred to a ward and
      came home three weeks after admission to hospital. During her stay in the
      intensive care unit, Lucy developed pneumonia, bilateral pleural effusions, acute
      renal failure and a pericardial effusion. Over the weeks and months that
      followed, Lucy began to describe her experiences and the impact that these have
      had on her. She described what it felt like to be a patient in the ICU and the
      challenges that she faced during her recovery. I am a Registered Nurse and at the
      time my wife was admitted to the ICU I had spent twenty years working within the
      field of intensive care. Until my wife had been admitted to ICU, I thought that I
      had a good appreciation of what it was like to be a patient or a relative in an
      intensive care unit. Having experienced critical care at first hand and having
      had an opportunity to reflect on what happened I now realise what little insight
      I had. I have now come to realise that as nurses in intensive care there is much
      we can do to alleviate the suffering and discomfort experienced by some of our
      patients and relatives. Perhaps by describing what happened, I will enable the
      reader to understand more clearly and to reflect on those factors which have a
      deep and lasting impact on patients and their relatives and which can be
      influenced by nurses at the bedside. For the purpose of this account, I have
      chosen to call my wife, Lucy.

PMID- 19853451
TI  - The C. elegans dosage compensation complex propagates dynamically and
      independently of X chromosome sequence.
AB  - BACKGROUND: The C. elegans dosage compensation complex (DCC) associates with both
      X chromosomes of XX animals to reduce X-linked transcript levels. Five DCC
      members are homologous to subunits of the evolutionarily conserved condensin
      complex, and two noncondensin subunits are required for DCC recruitment to X.
      RESULTS: We investigated the molecular mechanism of DCC recruitment and spreading
      along X by examining gene expression and the binding patterns of DCC subunits in
      different stages of development, and in strains harboring X;autosome (X;A)
      fusions. We show that DCC binding is dynamically specified according to gene
      activity during development and that the mechanism of DCC spreading is
      independent of X chromosome DNA sequence. Accordingly, in X;A fusion strains, DCC
      binding propagates from X-linked recruitment sites onto autosomal promoters as a
      function of distance. Quantitative analysis of spreading suggests that the
      condensin-like subunits spread from recruitment sites to promoters more readily
      than subunits involved in initial X targeting. CONCLUSIONS: A highly conserved
      chromatin complex is appropriated to accomplish domain-scale transcriptional
      regulation during C. elegans development. Unlike X recognition, which is
      specified partly by DNA sequence, spreading is sequence independent and coupled
      to transcriptional activity. Similarities to the X recognition and spreading
      strategies used by the Drosophila DCC suggest mechanisms fundamental to
      chromosome-scale gene regulation.

PMID- 19853453
TI  - Seating and pressure ulcers: clinical practice guideline.
AB  - Pressure ulcers (bedsores) often develop following prolonged sitting especially
      where people are immobile or are unable to feel discomfort due to injury or
      disease. This guideline provides health professionals with specific
      recommendations intended to minimise any risk of developing pressure ulcers when
      their clients are seated. The guideline covers sitting when people are acutely
      ill in hospital and, more commonly, where people have a long-term need for
      prolonged sitting for example after spinal injury. Particular focus is placed
      upon the need to make sure the physical size and shape of the seat is appropriate
      for the seated individual. Guidance is provided upon areas where seated
      individuals require information to help them minimise pressure ulcer development.
      The advantages and disadvantages of different cushion materials are described.

PMID- 19853454
TI  - Postural sway in low back pain: Effects of dual tasks.
AB  - Recurrence quantification analysis (RQA), a nonlinear method of postural
      analysis, was used to explore the effects of dual-tasking on postural performance
      in people with nonspecific low back pain (LBP) compared with healthy
      participants. Postural performance was quantified by RQA % recurrence, %
      determinism, entropy and trend. People with nonspecific LBP (n=22) and unimpaired
      individuals (n=22) randomly performed quiet standing tasks with three levels of
      difficulty (rigid-surface eyes open, rigid-surface eyes closed and foam-surface
      eyes closed). These tasks were performed in isolation or concurrently with an
      easy or difficult cognitive task. Increasing postural difficulty was associated
      with higher % determinism, higher entropy and lower trend in anteroposterior (AP)
      and mediolateral (ML) directions in people with LBP and healthy participants. All
      RQA variables in the ML direction decreased as cognitive conditions became more
      difficult. Significant interactions between group and cognitive difficulty were
      shown for % recurrence, % determinism and trend in the AP direction. While
      healthy participants decreased % recurrence and trend by increasing the level of
      cognitive difficulty, the LBP patients did not. This preliminary study suggests
      that LBP may be one factor that modulates the posture-cognition interaction.

PMID- 19853455
TI  - Quantification of soft tissue artifact in lower limb human motion analysis: a
      systematic review.
AB  - This systematic review critically evaluates the quantification of soft tissue
      artifact (STA) in lower limb human motion analysis. It has a specific focus on
      assessing the quality of previous studies and comparing quantitative results. A
      specific search strategy identified 20 published articles or abstracts that
      fulfilled the selection criteria. The quality of the articles was evaluated using
      a customised critical appraisal tool. Data extraction tools were used to identify
      key aspects reported in the articles. Most studies had small sample sizes of
      mostly young, slim participants. Eleven of the reviewed articles used physically
      invasive techniques to assess STA. STA was found to reach magnitudes of greater
      than 30 mm on the thigh segment, and up to 15 mm on the tibia. The range of soft
      tissue artifact reached greater than 25 mm in some cases when comparing the
      results of reviewed studies.

PMID- 19853456
TI  - Bacterial tyrosine kinases: novel targets for antibacterial therapy?
AB  - The resistance of pathogenic bacteria to current antibiotics has become a crucial
      public health problem. To combat this resistance, there is a constant need for
      antibacterial drugs with new modes of action on therapeutic targets. Recent data
      have shown that a variety of cellular processes essential for bacterial survival
      and virulence are regulated by the phosphorylation of certain endogenous proteins
      catalyzed by specific tyrosine kinases. In this article, I highlight a selection
      of recent findings that confirm the central role of protein tyrosine
      phosphorylation in the control of bacterial physiology. Based on this knowledge,
      potential applications in the discovery of novel antibiotics are proposed.

PMID- 19853457
TI  - Actinobacteria as mutualists: general healthcare for insects?
AB  - Mutualistic microorganisms are well known to play a key role in providing
      nutrients for successful growth and reproduction in many insects. Several recent
      studies indicate that they can be equally important for the protection of the
      host and its nutritional resources against pathogen attack. In particular,
      different actinobacteria have been found to defend ants, beetles and wasps
      against detrimental microorganisms by producing antibiotics. The extraordinary
      abilities of actinobacteria to exploit a wide variety of carbon and nitrogen
      sources and their extensive repertoire of secondary metabolites probably
      predispose this group to engage in protective symbioses. Defensive mutualisms
      with actinobacteria might constitute a general and widespread theme in the
      ecology and evolution of arthropods, and the study of the secondary metabolites
      involved promises to uncover novel drug candidates for human medicine.

PMID- 19853458
TI  - N-glycan structures: recognition and processing in the ER.
AB  - The processing of N-linked glycans determines secretory protein homeostasis in
      the eukaryotic cell. Folding and degradation of glycoproteins in the endoplasmic
      reticulum (ER) are regulated by molecular chaperones and enzymes recruited by
      specific oligosaccharide structures. Recent findings have identified several
      components of this protein quality control system that specifically modify N
      linked glycans, thereby generating oligosaccharide structures recognized by
      carbohydrate-binding proteins, lectins. In turn, lectins direct newly synthesized
      polypeptides to the folding, secretion or degradation pathways. The "glyco-code
      of the ER" displays the folding status of a multitude of cargo proteins.
      Deciphering this code will be instrumental in understanding protein homeostasis
      regulation in eukaryotic cells and for intervention because such processes can
      have crucial importance for clinical and industrial applications.

PMID- 19853460
TI  - The selective quantification of iron by hexadentate fluorescent probes.
AB  - The synthesis of four hexadentate fluorescent probes is described, where the
      fluorescent moiety is based on either coumarin or fluorescein and the chelating
      moiety is based on either 3-hydroxypyridin-4-one or 3-hydroxypyran-4-one. The
      fluorescence is quenched when the probe chelating moieties bind iron. The probes
      were found to be selective for iron over other metals such as Cu, Zn, Ni, Mn and
      Co. The effect of Cu on fluorescence quenching can be eliminated in the presence
      of N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine. Competition studies
      demonstrate that the exchange of iron between pyridinone-based probes and
      apotransferrin is very slow. The ability to scavenge iron from oligomeric
      iron(III) citrate complexes demonstrate that the pyridinone probes scavenges iron
      faster than deferiprone and desferrioxamine. The fluorescence intensity of the
      fluorescein-based probe is quantitatively related to the iron concentration with
      the limit of detection being 10(-8)M.

PMID- 19853459
TI  - Natural and synthetic 2'-hydroxy-chalcones and aurones: synthesis,
      characterization and evaluation of the antioxidant and soybean lipoxygenase
      inhibitory activity.
AB  - A series of 2'-hydroxy-chalcones and their oxidative cyclization products,
      aurones, have been synthesized and tested for their antioxidant and lipoxygenase
      inhibitory activity. The natural product aureusidin (31) was synthesized in high
      yield by a new approach. An extensive structure-relationship study was performed
      and revealed that several chalcones and aurones possess an appealing
      pharmacological profile combining high antioxidant and lipid peroxidation
      activity with potent soybean LOX inhibition.

PMID- 19853461
TI  - Structural optimization of a CXCR2-directed antagonist that indirectly inhibits
      gamma-secretase and reduces Abeta.
AB  - Amyloid beta (Abeta), a key molecule in the pathogenesis of Alzheimer's disease
      (AD), is derived from the amyloid precursor protein (APP) by sequential
      proteolysis via beta- and gamma-secretases. Because of their role in generation
      of Abeta, these enzymes have emerged as important therapeutic targets for AD. In
      the case of gamma-secretase, progress has been made towards designing potent
      inhibitors with suitable pharmacological profiles. Direct gamma-secretase
      inhibitors are being evaluated in clinical trials and new strategies are being
      explored to block gamma-secretase activity indirectly as well. In this regard, we
      have previously reported an indirect regulation of gamma-secretase through
      antagonism of CXCR2, a G-protein coupled receptor (GPCR). We demonstrated that N
      (2-hydroxy-4-nitrophenyl)-N'-(2-bromophenyl)urea (SB225002), a selective
      inhibitor of CXCR2 also plays a role in an indirect inhibition of gamma
      secretase. Furthermore, we reported a approximately 5-fold difference in the
      selective inhibition of APP versus Notch processing via gamma-secretase following
      treatment with SB225002. Herein we describe the synthesis and optimization of
      SB225002. By determination of the structure-activity relationship (SAR), we
      derived small molecules that inhibit Abeta40 production with IC(50) values in the
      sub-micromolar range in a cell-based assay and also validated the potential of
      CXCR2 as a new target for therapeutic intervention in AD.

PMID- 19853462
TI  - 4-(3-aryloxyaryl)quinoline alcohols are liver X receptor agonists.
AB  - A series of 4-(3-aryloxyaryl)quinolines with alcohol substituents on the terminal
      aryl ring was prepared as potential LXR agonists, in which an alcohol group
      replaced an amide in previously reported amide analogs. High affinity LXR ligands
      with excellent agonist potency and efficacy in a functional model of LXR activity
      were identified, demonstrating that alcohols can substitute for amides while
      retaining LXR activity. The most potent compound was 5b which had an IC(50)=3.3
      nM for LXRbeta binding and EC(50)=12 nM (122% efficacy relative to T0901317) in
      an ABCA1 mRNA induction assay in J774 mouse cells.

PMID- 19853464
TI  - Response to letter to the editor published in ARI 67 (2009) 206-207.

PMID- 19853463
TI  - Radium-226 concentration in spring water sampled in high radon regions.
AB  - Water (226)Ra concentration in springs was measured in regions with high indoor
      radon: Ural, North Caucasus (Russia), Niska Banja (Serbia), Piestany (Slovakia),
      and Issyk-Kul (Kyrgyzstan). This paper presents the results for (226)Ra
      concentration above 0.03 Bq l(-1). Radium in water could indicate indoor radon
      problem in the region and water investigation is useful at the initial stage of
      radon survey. Even low (226)Ra concentration in water (0.1-0.6 Bq l(-1)) caused
      high (226)Ra activity in travertine (up to 1500 Bq kg(-1)), which resulted in
      indoor radon concentration above 2000 Bq m(-3) (Niska Banja).

PMID- 19853465
TI  - Radiation sources in the environment near NPP Temelin.
AB  - A widely discussed question is how much a nuclear power plant really contributes
      to irradiation of the people living in its vicinity. A number of laboratory and
      in situ measurements were performed in the area surrounding NPP Temelin, on the
      basis of which we can specify the irradiation of this area from various sources.
      The evaluation includes the contributions from natural sources, such as radon,
      terrestrial radiation and cosmic radiation, together with the contribution from
      inhalation and ingestion of radionuclides. Medical irradiation and nuclear
      fallout are also included.

PMID- 19853466
TI  - Pharmacological preconditioning of the heart during surgery.

PMID- 19853467
TI  - Postoperative consumption of opioid analgesics following correction of pectus
      excavatum is influenced by pectus severity: a single-centre study of 236 patients
      undergoing minimally invasive correction of pectus excavatum.
AB  - OBJECTIVE: Surgical correction of pectus excavatum (PE) is primarily performed to
      achieve cosmetic and psychological benefits for the patient. Minimally invasive
      repair of PE is often associated with severe postoperative pain. This study
      estimates the effect of the severity of PE on the postoperative consumption of
      opioid analgesics following this procedure to optimise pain management. METHODS:
      A retrospective study was conducted on 236 consecutive patients undergoing
      minimally invasive repair of PE from 2005 to 2008. The collected data included
      depth of preoperative pectus excavation, patient demographics, peri- and
      postoperative information, including data on pain management. The consumption of
      opioid analgesics was registered after discontinuation of epidural analgesia and
      other types of opioid analgesics used during the study period were converted to
      morphine equivalents. Multiple linear regression analysis was performed to
      estimate the effect of the severity of PE on the postoperative consumption of
      opioid analgesics and to adjust for potential confounding. RESULTS: The total
      morphine consumption following minimally invasive repair of PE ranged between 20
      and 370 mg day(-1). Multiple linear regression analysis explained approximately
      30% of the variation in daily morphine consumption (R-squared=0.2957). There was
      a significant positive linear relationship between pectus severity and the daily
      consumption of morphine. Thus, postoperative consumption of morphine increased by
      6% (95% confidence interval (CI): 0.3-11%) when preoperative PE depth
      deteriorated with 1cm. CONCLUSION: This study confirms that pectus severity has a
      significant impact on the consumption of opioid analgesics following minimally
      invasive repair of PE. We conclude that knowledge of pectus severity might be
      useful in the prediction of the expected morphine consumption in future patients,
      especially during the critical transition period from epidural analgesia to oral
      analgesia.

PMID- 19853468
TI  - Preoperative atrial fibrillation decreases event-free survival following cardiac
      surgery: when a good story is not compelling.

PMID- 19853469
TI  - Right coronary artery to coronary sinus fistula.

PMID- 19853470
TI  - Femoro-axillary cardiopulmonary bypass for giant abdominal aortic aneurysm repair
      prior to staged cardiac operation for ischaemic cardiomyopathy.
AB  - The optimal surgical management of simultaneous abdominal aortic aneurysm and
      cardiac disease remains a major challenge in case of larger aneurysms and severe
      cardiac disease. In case of symptomatic aneurysms or impending rupture, a single
      stage combined operation is the most widely accepted procedure. We report the
      successful use of closed-chest cardiopulmonary bypass, with femoral venous and
      axillary arterial peripheral cannulation, to support cardiac function on the
      beating heart during resection of a giant abdominal aortic aneurysm and ischaemic
      cardiomyopathy. One month later, the patient underwent a second-stage deferred
      cardiac operation, consisting of triple coronary bypass grafting, undersized
      mitral annuloplasty and epicardial left ventricular lead implantation for cardiac
      resynchronisation therapy.

PMID- 19853471
TI  - Isomeric discrimination and quantification of thyroid hormones, T3 and rT3, by
      the single ratio kinetic method using electrospray ionization mass spectrometry.
AB  - The single ratio kinetic method is applied to the discrimination and
      quantification of the thyroid hormone isomers, 3,5,3'-triiodothyronine and
      3,3',5'-triiodothyronine, in the gas phase, based on the kinetics of the
      competitive unimolecular dissociations of singly charged transition-metal ion
      bound trimeric complexes [M(II)(A)(ref*)(2)-H](+) (M(II) = divalent transition
      metal ion; A = T(3) or rT(3); ref* = reference ligand). The trimeric complex ions
      are generated using electrospray ionization mass spectrometry and the ions
      undergo collisional activation to realize isomeric discrimination from the
      branching ratio of the two fragment pathways that form the dimeric complexes
      [M(II)(A)(ref*)-H](+) and [M(II)(ref*)(2)-H](+). The ratio of the individual
      branching ratios for the two isomers R(iso) is found strongly dependent on the
      references and the metal ions. Various sets are tried by choosing the reference
      from amino acids, substituted amino acids, and dipeptides in combination with the
      central metal ion chosen from five transition-metal ions (Co(II), Cu(II), Mn(II),
      Ni(II), and Zn(II)) for the complexes in this experiment. The results are
      compared in terms of the isomeric discrimination for the T(3)/rT(3) pair.
      Calibration curves are constructed by relating the ratio of the branching ratios
      against the isomeric composition of their mixture to allow rapid quantitative
      isomer analysis of the sample pair. Furthermore, the instrument-dependence of
      this method is investigated by comparing the two sets of results, one obtained
      from a quadrupole ion trap mass spectrometer and the other from a quadrupole time
      of-flight mass spectrometer.

PMID- 19853472
TI  - Consideration on a few aspects of the stability studies post licensure.
AB  - Stability studies represent a significant workload for both manufacturers and
      regulatory reviewers and therefore a careful selection of the study design and of
      the stability indicator test is required to make sure that the study will provide
      the relevant information. Moreover, alternatives to the existing regulatory
      approaches should be favoured in order to better or quicker analyze the impact of
      a specific change. In this article, examples of alternative approaches are given.
      For the stability monitoring study, emphasis is put on the bulk stability
      program. Concerning comparability stability study, two case studies illustrating
      how accelerated stability studies could be used to support manufacturing changes
      are presented.

PMID- 19853473
TI  - Delayed abdominal muscle onsets and self-report measures of pain and disability
      in chronic low back pain.
AB  - OBJECTIVE: The objective of this study was the measure the onset time of the
      transverse abdominis (TA) muscle during rapid unilateral shoulder movements in
      individuals with chronic low back pain (LBP), and to evaluate the relationship
      between latency times and self-report measures of pain and disability. DESIGN:
      Descriptive cross-sectional study. SETTING: University laboratory. PARTICIPANTS:
      Eighty individuals with chronic LBP of a non-specific origin (males n=44, females
      n=36). MAIN OUTCOME MEASURES: Responses of the right and left surface TA/internal
      obliques were measured using surface electromyography (EMG) during rapid
      unilateral shoulder flexion, abduction, and extension. Pain intensity was
      measured using a visual analog scale (VAS), and disability with the Oswestry
      disability index (ODI). RESULTS: Seventy-five percent of individuals were
      identified as lacking feedforward activation. A significant sidexdirection main
      effect was identified, with the ipsilateral latency more delayed in flexion and
      abduction (F(2316)=58.2, p<0.001). Individuals without feedforward activation had
      lower ODI scores (23.2+/-6.9% vs 31.0+/-9.2%, mean difference 7.8%, 95% CI 3.9 to
      11.6%, p<0.001). Regression analysis found that 17% of the variance in VAS scores
      for the entire sample (n=80) were explained by the latency times measured. This
      relationship was stronger when the sample was separated into individuals who did
      (n=20), and did not (n=60) have feedforward activation. CONCLUSION: Deep
      abdominal muscle onsets during rapid limb movement were significantly associated
      with self-rated pain scores. Seventy-five percent of individuals with chronic non
      specific LBP exhibited delayed activation. No evidence has been provided in this
      study to support, or refute the use of specific localized deep abdominal
      contractions for exercise rehabilitation programs.

PMID- 19853474
TI  - Underreporting of energy intake in peritoneal dialysis patients.
AB  - OBJECTIVES: This study aimed to assess the prevalence of underreporting among
      patients treated by peritoneal dialysis (PD), and to investigate whether the
      reported energy intake is influenced by overweight status in this population.
      DESIGN: This was a prospective, observational study. SETTING: This study took
      place at the Dialysis Unit of the Nephrology Division, Federal University of Sao
      Paulo-Oswaldo Ramos Foundation, Sao Paulo, Brazil. PATIENTS: Forty adult patients
      were recruited: 24 men and 16 women; age, 53.4+/-16.5 years; body mass index
      (BMI), 25.1+/-3.8 kg/m(2) (x+/-SD); median duration of dialysis, 19 months
      (range, 3 to 101 months). Only patients on PD >3 months, free of peritonitis for
      at least 3 months, without catabolic conditions and with normal thyroid function,
      were included. METHODS: Energy intake was evaluated using a 3-day food record.
      Resting energy expenditure (REE) was measured by indirect calorimetry. Body
      composition was assessed using dual-energy x-ray absorptiometry. The total energy
      (TE) offered was considered the sum of energy intake plus energy provided by
      glucose absorption. All measurements were collected at baseline and after 6
      months. Underreporting of energy intake was considered to have occurred when the
      TE/REE ratio was <1.40. RESULTS: The TE/REE ratio was 1.35+/-0.31. Twenty-one
      patients (52.5%) had a TE/REE ratio <1.40. The TE/REE ratio correlated negatively
      with BMI (r=-0.52, P < .01), and positively with duration of dialysis (r=0.44, P
      < .01). No correlation was found between TE/REE ratio and any other variables.
      Patients were divided into two groups according to BMI <25 kg/m(2) and BMI > or
      =25 kg/m(2). The majority of patients (83.3%) in the higher BMI group had a
      TE/REE ratio <1.40. In a logistic regression analysis, using TE/REE ratio <1.40
      or > or =1.40 as the dependent variable, BMI> or =25 kg/m2 was the only
      determinant of energy underreporting. After 6 months of follow-up, no change in
      either body weight or BMI was evident. CONCLUSIONS: This study showed that a
      significant number of PD patients underreported the energy intake evaluated by 3
      day food diaries. This finding was evidenced particularly in overweight patients.

PMID- 19853475
TI  - Nutritional management of hyperkalemic infants with chronic kidney disease, using
      adult renal formulas.
AB  - OBJECTIVE: This study sought to evaluate the use of adult renal formulas in
      hyperkalemic infants with chronic kidney disease (CKD). DESIGN: This was a
      retrospective, single-center cohort study. SETTING: This study took place at the
      Department of Pediatric Nephrology, Dialysis, and Transplantation at Helen DeVos
      Children's Hospital (Grand Rapids, MI). PATIENTS: Seven hyperkalemic infants
      (mean age, 6.9 months) comprised the study population: 29% with stage 3 CKD, 29%
      with stage 4 CKD, and 42% with stage 5 CKD. INTERVENTION: Infants were
      empirically treated with adult renal formulas for an average duration of 9.6
      months. Six of seven infants were started on breast milk or infant formula
      (Similac PM 60/40, Abbott Laboratories, Columbus, OH), but because of inadequate
      growth and hyperkalemia, were transitioned to adult renal formulas (Suplena,
      Abbott Laboratories, Columbus, OH; Nepro, Abbott Laboratories, Columbus, OH;
      and/or Renalcal, Nestle Nutrition, Minnetonka, MN). One infant received adult
      renal formula at birth. MAIN OUTCOME MEASURES: The outcome measures included
      amount of potassium delivered by infant and adult renal formulas, level of serum
      potassium, and anthropometric measurements adjusted for age and gender (z
      scores). RESULTS: The transition from infant to adult renal formula resulted in a
      decrease in mean amount of potassium delivered by formula (from 2.6 to 1.0
      mEq/kg/day, P < .001) and a decrease in mean serum potassium (from 5.1 to 4.0
      mmol/L, P < .01). During treatment with adult renal formula, the infants
      demonstrated a significant increase in mean weight z-score (from -1.0 to 0.5, P <
      .01), height z-score (from -1.9 to -0.5, P < .01), and head-circumference z-score
      (from -1.5 to -1.0, P=.03). Adult renal formulas were well-tolerated.
      CONCLUSIONS: Hyperkalemic infants with CKD can be nutritionally managed on adult
      renal formula.

PMID- 19853476
TI  - Sources of variation in estimates of lean body mass by creatinine kinetics and by
      methods based on body water or body mass index in patients on continuous
      peritoneal dialysis.
AB  - OBJECTIVE: We identified factors that account for differences between lean body
      mass computed from creatinine kinetics (LBM(cr)) and from either body water
      (LBM(V)) or body mass index (LBM(BMI)) in patients on continuous peritoneal
      dialysis (CPD). DESIGN: We compared the LBM(cr) and LBM(V) or LBM(BMI) in
      hypothetical subjects and actual CPD patients. PATIENTS: We studied 439 CPD
      patients in Albuquerque, Pittsburgh, and Toronto, with 925 clearance studies.
      INTERVENTION: Creatinine production was estimated using formulas derived in CPD
      patients. Body water (V) was estimated from anthropometric formulas. We
      calculated LBM(BMI) from a formula that estimates body composition based on body
      mass index. In hypothetical subjects, LBM values were calculated by varying the
      determinants of body composition (gender, diabetic status, age, weight, and
      height) one at a time, while the other determinants were kept constant. In actual
      CPD patients, multiple linear regression and logistic regression were used to
      identify factors associated with differences in the estimates of LBM
      (LBM(cr)<LBM(V), or LBM(cr)<LBM(BMI)). MAIN OUTCOME MEASURE: We sought predictors
      of the differences LBM(V) - LBM(cr) and LBM(BMI) - LBM(cr). RESULTS: Both LBM(V)
      (regardless of formula used to estimate V) and LBM(BMI) exceeded LBM(cr) in
      hypothetical subjects with average body compositions. The sources of differences
      between LBM estimates in this group involved differences in the coefficients
      assigned to gender, age, height, weight, presence or absence of diabetes, and
      serum creatinine concentration. In CPD patients, mean LBM(V) or LBM(BMI) exceeded
      mean LBM(cr) by 6.2 to 6.9 kg. For example, the LBM(V) obtained from one
      anthropometric formula was 50.4+/-10.4 kg and the LBM(cr) was 44.1+/-13.6 kg (P <
      .001), whereas among the 925 clearance studies, only 216 (23.3%) had
      LBM(cr)>LBM(V). The differences in determinants of body composition between
      groups with high versus low LBM(cr) were similar in hypothetical and actual CPD
      patients. Multivariate analysis in actual CPD patients identified serum
      creatinine, height, age, gender, weight, and body mass index as predictors of the
      differences LBM(V)-LBM(cr) and LBM(BMI)-LBM(cr). CONCLUSIONS: Overhydration is
      not the sole factor accounting for the differences between LBM(cr) and either
      LBM(V) or LBM(BMI) in CPD patients. These differences also stem from the
      coefficients assigned to major determinants of body composition by the formulas
      estimating LBM.

PMID- 19853477
TI  - Serum carboxymethyl-lysine, a dominant advanced glycation end product, is
      associated with chronic kidney disease: the Baltimore longitudinal study of
      aging.
AB  - OBJECTIVE: Advanced glycation end products (AGEs) are modifiable risk factors for
      renal disease that were primarily studied in persons with diabetes or endstage
      renal disease. Our objective was to characterize the relationship between AGEs
      and renal function in community-dwelling adults. DESIGN: The presence of serum L
      carboxymethyl-lysine (CML), a dominant AGE, was compared with renal function in a
      cross-sectional analysis. SETTING: This study was part of the Baltimore
      Longitudinal Study of Aging in Baltimore, Maryland. PATIENTS OR OTHER
      PARTICIPANTS: Participants included community-dwelling men and women, aged 26 to
      93 years, seen during a regular follow-up visit to the Baltimore Longitudinal
      Study of Aging between 2002 and 2007. MAIN OUTCOME MEASURES: The main outcome
      measures included chronic kidney disease (CKD) at stage >/=3 of the National
      Kidney Foundation classification (estimated glomerular filtration rate [eGFR]
      of<60 mL/minute/1.73 m(2)) and eGFR. RESULTS: Of 750 adults, 121 (16.1%) had CKD.
      Serum CML was associated with CKD (odds ratio expressed per one standard
      deviation, 1.37; 95% confidence interval, 1.11 to 1.67; P=.003) in a multivariate
      logistic regression model adjusting for age, race, smoking, and chronic diseases.
      Serum CML was associated with eGFR (mL/minute/1.73 m(2)) (beta=-2.21, standard
      error=0.57, P=.0001) in a multivariate linear regression model, adjusting for
      age, race, smoking, and chronic diseases. After excluding patients with diabetes,
      serum CML was associated with CKD (odds ratio per one standard deviation, 1.38;
      95% confidence interval, 1.12 to 1.70; P=.003) and eGFR (beta=-2.09, standard
      error=0.59, P=.0005), adjusting for the same covariates. CONCLUSION: Serum CML, a
      dominant AGE, is independently associated with CKD and eGFR.

PMID- 19853478
TI  - Changing trends in infectious disease in heart transplantation.
AB  - BACKGROUND: During the past 25 years, advances in immunosuppression and the use
      of selective anti-microbial prophylaxis have progressively reduced the risk of
      infection after heart transplantation. This study presents a historical
      perspective of the changing trends of infectious disease after heart
      transplantation. METHODS: Infectious complications in 4 representative eras of
      immunosuppression and anti-microbial prophylaxis were analyzed: (1) 38 in the pre
      cyclosporine era (1978-1980), (2) 72 in the early cyclosporine era (1982-1984),
      where maintenance immunosuppression included high-dose cyclosporine and
      corticosteroid therapy; (3) 395 in the cyclosporine era (1988-1997), where
      maintenance immunosuppression included cyclosporine, azathioprine, and lower
      corticosteroid doses; and (4) 167 in the more recent era (2002-2005), where
      maintenance immunosuppression included cyclosporine and mycophenolate mofetil.
      RESULTS: The overall incidence of infections decreased in the 4 cohorts from 3.35
      episodes/patient to 2.03, 1.35, and 0.60 in the more recent cohorts (p < 0.001).
      Gram-positive bacteria are emerging as the predominant cause of bacterial
      infections (28.6%, 31.4%, 51.0%, 67.6%, p = 0.001). Cytomegalovirus infections
      have significantly decreased in incidence and occur later after transplantation
      (88 +/- 77 days, pre-cyclosporine era; 304 +/- 238 days, recent cohort; p <
      0.001). Fungal infections also decreased, from an incidence of 0.29/patient in
      the pre-cyclosporine era to 0.08 in the most recent era. A major decrease in
      Pneumocystis jiroveci and Nocardia infections has also occurred. CONCLUSIONS: The
      overall incidence and mortality associated with infections continues to decrease
      in heart transplantation and coincides with advances in immunosuppression, the
      use of selective anti-microbial prophylaxis, and more effective treatment
      regimens.

PMID- 19853479
TI  - The efficacy of photopheresis for bronchiolitis obliterans syndrome after lung
      transplantation.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) has been used to treat acute and
      chronic rejection after solid organ transplantation. However, data supporting the
      use of ECP for bronchiolitis obliterans syndrome (BOS) after lung transplantation
      are limited. METHODS: We retrospectively analyzed the efficacy and safety of ECP
      for progressive BOS at our institution. Between January 1, 2000, and December 31,
      2007, 60 lung allograft recipients were treated with ECP for progressive BOS.
      RESULTS: During the 6-month period before the initiation of ECP, the average rate
      of decline in forced expiratory volume in 1 second (FEV(1)) was -116.0 ml/month,
      but the slope decreased to -28.9 ml/month during the 6-month period after the
      initiation of ECP, and the mean difference in the rate of decline was 87.1
      ml/month (95% confidence interval, 57.3-116.9; p < 0.0001). The FEV(1) improved
      in 25.0% of patients after the initiation of ECP, with a mean increase of 20.1
      ml/month. CONCLUSIONS: ECP is associated with a reduction in the rate of decline
      in lung function associated with progressive BOS.

PMID- 19853482
TI  - Radiographic anatomy of the rabbit skull with particular reference to the
      tympanic bulla and temporomandibular joint: Part 1: Lateral and long axis
      rotational angles.
AB  - Radiography is frequently used to investigate otitis media and dental disease in
      rabbits, although there are few detailed reports regarding the radiographic
      anatomy of the rabbit skull. The aim of this study was to document rabbit skull
      radiographic anatomy, with particular reference to the tympanic bulla (TB) and
      temporomandibular joint (TMJ), and to identify views that allowed optimal
      assessment of these areas. Equipment was used that allowed repeatable positioning
      of skulls at known rotational angles in lateral (lateral to rostrocaudal) and
      long axis (lateral to ventrodorsal) directions. The views were repeated with lead
      markers attached to anatomical features and cadaver heads. The TB could be best
      examined between 30 degrees  and 60 degrees  in both planes. The TMJ was best
      visualised between 70 degrees  and 90 degrees  in a lateral direction,
      particularly along a true rostrocaudal plane, but could not be imaged well at any
      of the long axis rotational angles. Similar images were obtained using cadavers.

PMID- 19853480
TI  - Hepatitis C treatment experiences and decision making among patients living with
      HIV infection.
AB  - Hepatitis C infection is a major problem for approximately 250,000 HIV-infected
      persons in the United States. Although HIV infection is well-controlled in most
      of this population, they suffer liver-associated morbidity and mortality.
      Conversely, hepatitis C virus (HCV) treatment uptake remains quite low (15%-30%).
      Therefore, the purpose of this qualitative study was to explore HCV treatment
      experiences and decision making in adults with HIV infection. The study sample
      included 39 coinfected adults; 16 in the HCV-treated cohort (who were interviewed
      a maximum of 3 times) and 23 in the HCV-nontreatment cohort. Analysis of
      interviews identified 2 treatment barriers (fears and vicarious experiences) and
      4 facilitating factors (experience with illness management, patient-provider
      relationships, gaining sober time, and facing treatment head-on). Analysis of
      these data also revealed a preliminary model to guide intervention development
      and theoretical perspectives. Ultimately, research is urgently needed to test
      interventions that improve HCV evaluation and treatment uptake among HIV-infected
      patients.

PMID- 19853483
TI  - Diffusion effects on the CPMG relaxation rate in a dipolar field.
AB  - The diffusion in the magnetic dipolar field around a sphere is considered. The
      diffusion is restricted to the space between two concentric spheres, where the
      inner sphere is the source of the magnetic dipolar field. Analytical expressions
      for the CPMG transverse relaxation rate as well as the free induction decay and
      the spin echo time evolution are given in the Gaussian approximation. The
      influence of the inter-echo time is analyzed. The limiting cases of small and
      large inter-echo times as well as the short and long time behavior are evaluated.

PMID- 19853484
TI  - Quantitative two-dimensional HSQC experiment for high magnetic field NMR
      spectrometers.
AB  - The finite RF power available on carbon channel in proton-carbon correlation
      experiments leads to non-uniform cross peak intensity response across carbon
      chemical shift range. Several classes of broadband pulses are available that
      alleviate this problem. Adiabatic pulses provide an excellent magnetization
      inversion over a large bandwidth, and very recently, novel phase-modulated pulses
      have been proposed that perform 90 degrees and 180 degrees magnetization
      rotations with good offset tolerance. Here, we present a study how these
      broadband pulses (adiabatic and phase-modulated) can improve quantitative
      application of the heteronuclear single quantum coherence (HSQC) experiment on
      high magnetic field strength NMR spectrometers. Theoretical and experimental
      examinations of the quantitative, offset-compensated, CPMG-adjusted HSQC (Q
      OCCAHSQC) experiment are presented. The proposed experiment offers a formidable
      improvement to the offset performance; (13)C offset-dependent standard deviation
      of the peak intensity was below 6% in range of+/-20 kHz. This covers the carbon
      chemical shift range of 150 ppm, which contains the protonated carbons excluding
      the aldehydes, for 22.3 T NMR magnets. A demonstration of the quantitative
      analysis of a fasting blood plasma sample obtained from a healthy volunteer is
      given.

PMID- 19853481
TI  - Interleukin-17 is required for T helper 1 cell immunity and host resistance to
      the intracellular pathogen Francisella tularensis.
AB  - The importance of T helper type 1 (Th1) cell immunity in host resistance to the
      intracellular bacterium Francisella tularensis is well established. However, the
      relative roles of interleukin (IL)-12-Th1 and IL-23-Th17 cell responses in
      immunity to F. tularensis have not been studied. The IL-23-Th17 cell pathway is
      critical for protective immunity against extracellular bacterial infections. In
      contrast, the IL-23-Th17 cell pathway is dispensable for protection against
      intracellular pathogens such as Mycobacteria. Here we show that the IL-23-Th17
      pathway regulates the IL-12-Th1 cell pathway and was required for protective
      immunity against F.tularensis live vaccine strain. We show that IL-17A, but not
      IL-17F or IL-22, induced IL-12 production in dendritic cells and mediated Th1
      responses. Furthermore, we show that IL-17A also induced IL-12 and interferon
      gamma production in macrophages and mediated bacterial killing. Together, these
      findings illustrate a biological function for IL-17A in regulating IL-12-Th1 cell
      immunity and host responses to an intracellular pathogen.

PMID- 19853485
TI  - Line-narrowing in proton-detected nitrogen-14 NMR.
AB  - In solids spinning at the magic angle, the indirect detection of single-quantum
      (SQ) and double-quantum (DQ) (14)N spectra (I=1) via spy nuclei S=1/2 such as
      protons can be achieved in the manner of heteronuclear single- or multiple
      quantum correlation (HSQC or HMQC) spectroscopy. The HMQC method relies on the
      excitation of two-spin coherences of the type T(11)(I)T(11)(S) and
      T(21)(I)T(11)(S) at the beginning of the evolution interval t(1). The spectra
      obtained by Fourier transformation from t(1) to omega(1) may be broadened by the
      homogenous decay of the transverse terms of the spy nuclei S. This broadening is
      mostly due to homonuclear dipolar S-S' interactions between the proton spy
      nuclei. In this work we have investigated the possibility of inserting rotor
      synchronized symmetry-based C or R sequences and decoupling schemes such as Phase
      Modulated Lee-Goldburg (PMLG) sequences in the evolution period. These schemes
      reduce the homonuclear proton-proton interactions and lead to an enhancement of
      the resolution of both SQ and DQ proton-detected (14)N HMQC spectra. In addition,
      we have investigated the combination of HSQC with symmetry-based sequences and
      PMLG and shown that the highest resolution in the (14)N dimension is achieved by
      using HSQC in combination with symmetry-based sequences of the R-type. We show
      improvements in resolution in samples of l-alanine and the tripeptide ala-ala-gly
      (AAG). In particular, for l-alanine the width of the (14)N SQ peak is reduced
      from 2 to 1.2 kHz, in agreement with simulations. We report accurate measurements
      of quadrupolar coupling constants and asymmetry parameters for amide (14)N in AAG
      peptide bonds.

PMID- 19853486
TI  - Recurrent isolated sixth nerve palsy after consecutive annual influenza
      vaccination in a child.

PMID- 19853487
TI  - Pomegranate extract induces apoptosis in human prostate cancer cells by
      modulation of the IGF-IGFBP axis.
AB  - The IGF axis is critical for the regulation of apoptosis in many human cancer
      cell lines. Recently, potent anti-tumorigenic effects of pomegranate juice and
      extracts have been reported. Consequently, pomegranate has potential not only as
      a treatment but also as a preventative measure against certain types of cancer,
      including prostate. In this study, we investigated the relationship between
      pomegranate-induced apoptosis in human prostate cancer cells and the IGF/IGFBP
      system. Treatment of LAPC4 prostate cancer cells with 10microg/ml POMx, a highly
      potent pomegranate extract prepared from skin and arils minus seeds and
      standardized to ellagitannin content (37% punicalagins by HPLC), resulted in
      inhibition of cell proliferation and induction of apoptosis. Interestingly, co
      treatment with POMx and IGFBP-3 revealed synergistic stimulation of apoptosis and
      additive inhibition of cell growth. Western blot analysis revealed that treatment
      with POMx or POMx/IGFBP-3 combination resulted in increased JNK phosphorylation,
      and decreased Akt and mTOR activation, consistent with a growth inhibitory, pro
      apoptotic function. We also investigated the relationship between IGF-1 and
      pomegranate-induced apoptosis in 22RV1 prostate cancer cells. Co-treatment with
      100ng/ml IGF-1 completely blocked apoptosis induction by POMx. In contrast, IGF-I
      failed to inhibit POMx-induced apoptosis in R(-) cells, suggesting the importance
      of IGF-IR. POMx-treatment decreased Igf1 mRNA expression in a dose-dependent
      manner indicating that its actions also involve tumor-specific suppression of IGF
      1. These studies revealed novel interactions between the IGF system and
      pomegranate-induced apoptosis.

PMID- 19853489
TI  - Usefulness of blood vessels as a DNA source for PCR-based genotyping based on two
      cases of corpse dismemberment.
AB  - The success of PCR-based genotyping of decomposed remains depends on the quality
      of extracted DNA. Hard tissues and muscles are preferred because of their DNA
      stability. However, in dismembered corpses the choice of a suitable DNA source is
      more limited. In short tandem repeat (STR) analysis in two cases of dismembered
      corpses, we found an advantage of using blood vessels over muscles. To confirm
      that blood vessels are better for STR typing compared to muscle, we collected
      nine sets of blood vessels and the adjacent muscle from six other decomposed
      remains and compared the STR profiles between the blood vessel and muscle
      samples. Better results for STR typing were obtained in blood vessels. Based on
      these results, we recommend use of blood vessels as material for PCR-based
      genotyping in identification of dismembered human remains with heavy postmortem
      changes.

PMID- 19853488
TI  - Alpha-1-antitrypsin deficiency and smoking as risk factors for mismatch repair
      deficient colorectal cancer: a study from the colon cancer family registry.
AB  - In a previous study, alpha-1-antitrypsin (A1AT) deficiency alleles were found to
      be over represented among individuals with microsatellite unstable (MSI-high)
      colorectal cancers, and this was most significant in former or current smokers.
      We evaluated this association in a larger case-control study, stratified by
      microsatellite instability phenotypes. Concordant with prior observations, gender
      (female) and smoking history were positively associated with colorectal cancers
      having an MSI-high phenotype. No difference in frequency of A1AT deficiency
      alleles was found between cases and controls, irrespective of the MSI subtype.

PMID- 19853490
TI  - Forensic age estimation in human skeletal remains: current concepts and future
      directions.
AB  - Skeletal identification has a long tradition in both physical and forensic
      anthropology. The process generally begins with formulation of a biological
      profile (osteobiography); specifically, estimation of sex, age, ethnicity and
      stature. The present paper briefly reviews a selection of the principal methods
      used for one aspect of the identification process; the estimation of personal
      age. It is well-documented that variability in the morphological features used to
      assess age in the human skeleton progressively increases from birth to old age.
      Thus choice of method is inherently related to whether unidentified remains are
      those of a juvenile or an adult. This review, therefore, considers methods
      appropriate for age estimation in both juvenile and adult remains; the former
      being primarily based on developmental, and the latter degenerative,
      morphological features. Such a review is timely as new methods are constantly
      being developed, concurrent with refinements to those already well established in
      mainstream anthropology.

PMID- 19853491
TI  - An efficient one-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone directly from
      acetophenones and aromatic aldehydes under ultrasound irradiation.
AB  - A convenient and efficient one-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone
      directly from acetophenones and aromatic aldehydes under ultrasound irradiation
      at room temperature has been described. In comparison to two-step methods, the
      present procedure has the advantages of mild conditions, shorter reaction time,
      without isolation of any intermediate, saves energy and no requirement of toxic
      solvent.

PMID- 19853492
TI  - Using sonochemistry for the fabrication of hollow ZnO microspheres.
AB  - Hollow ZnO microspheres assembled by nanoparticles have been prepared by a
      sonochemical synthesis at room temperature using carbon spheres as template. The
      growth process of the precursor was investigated. The prepared hollow spheres
      were characterized by X-ray diffraction (XRD), field-emission scanning electron
      microscopy (FE-SEM), high-resolution transmission electron microscopy (HRTEM).
      The diameter of the obtained hollow spheres is about 500nm, and the walls are
      composed of numerous ZnO aggregate nanocrystallines with diameters of 90nm. A
      possible growth mechanism for the formation of ZnO microspheres has been
      proposed, in which carbon spheres play a crucial role in the formation of the
      wurtzite hollow ZnO microspheres. The specific structure of the hollow spheres
      may find applications in nanoelectronics, nanophotonics and nanomedicine.

PMID- 19853493
TI  - When more is better: multigene engineering in plants.
AB  - The genomics revolution has taught us that a great deal of information can be
      derived from studying many genes or proteins at the same time. We are beginning
      to see this approach blossoming in applied research. Instead of attempting to
      generate useful transgenic plants by introducing single genes, we now see an
      increasing number of researchers embracing multigene transfer (MGT) as an
      approach to generate plants with more ambitious phenotypes. MGT allows
      researchers to achieve goals that were once impossible - the import of entire
      metabolic pathways, the expression of entire protein complexes, the development
      of transgenic crops simultaneously engineered to produce a spectrum of added
      value compounds. The potential appears limitless.

PMID- 19853494
TI  - Carbohydrate arrays: recent developments in fabrication and detection methods
      with applications.
AB  - Carbohydrate arrays can provide facile analyses of carbohydrate-binding proteins,
      antibodies in serum, and enzyme activities with minimal quantities of sugar
      samples. Recent developments in detection methods for carbohydrate arrays,
      especially surface plasmon resonance (SPR) and mass spectrometry, have enabled
      not only qualitative but in some cases quantitative data analysis in a variety of
      multivalent display formats. These advancements make diagnostic tools based on
      carbohydrate arrays more promising for infectious disease detection, cancer
      monitoring, and vaccine development.

PMID- 19853495
TI  - The promise and challenge of '-omic' approaches.

PMID- 19853496
TI  - Leaf development: what it needs to be complex.
AB  - Formation of dissected compound leaves involves the transient maintenance of an
      indeterminate environment and the generation of new growth axes that will
      generate leaflets. Recent work has revealed additional multi-layered mechanisms
      controlling the activities of the KNOXI homeodomains factors that play a
      prominent role in the control of indeterminacy associated with compound leaf
      development. Patterning and individualisation of the leaflets has been shown to
      involve gradients of the phytohormone auxin and the contribution of the NAM/CUC3
      boundary genes. Identification of these novel actors governing compound leaf
      development opens the opportunity for further comparative studies aimed at
      understanding the molecular basis of leaf shape evolution.

PMID- 19853497
TI  - All in a spin: centrifugal organ formation and floral patterning.
AB  - Understanding floral patterning is a primary goal in plant biology, yet the
      temporal sequence of organ development is rarely factored into developmental
      models. In flowers, occasional examples of centrifugal or basipetal organ
      initiation, both within organ zones (intrazonal) and between them (interzonal),
      present a paradox with respect to developmental models. A centripetal/acropetal
      sequence of floral organ initiation is ancestral in angiosperms, but
      centrifugal/basipetal development has evolved many times, indicating that these
      apparently major developmental shifts have relatively simple genetic triggers.
      Review of the sequence of organ initiation in angiosperms supports evidence that
      the four floral organ types develop independently of each other, in response to
      genetic factors that predetermine radial patterning.

PMID- 19853499
TI  - The role of sex in fungal evolution.
AB  - Sex in fungi is often associated with dispersal and dormancy, but in many species
      is not required for reproduction, and its evolutionary genetic role is unclear.
      Sex can accelerate adaptation to a new environment, and recombination in
      Saccharomyces cerevisiae, though historically rare, has had a prominent role in
      the origins of many sequenced strains, in particular the origin of clinical
      strains from domesticated ancestors. Sex and recombination have recently been
      discovered in several human pathogens that were long thought to be asexual, but
      so far there is no compelling evidence that it plays an important genetic role in
      their adaptation. The self-compatible (homothallic) sexual systems of many fungi
      severely limit their potential for recombination, but increase the rate at which
      they can segregate new adaptive mutations into homozygotes, a possible benefit of
      sex that has received much less attention than recombination.

PMID- 19853498
TI  - White-opaque switching in Candida albicans.
AB  - The human commensal yeast Candida albicans undergoes an epigenetic switch between
      two distinct types of cells, referred to as white and opaque. These two cell
      types differ in many respects, including their cell and colony morphologies,
      their metabolic states, their mating behaviors, their preferred niches in the
      host, and their interactions with the host immune system. Each of the two cell
      types is heritable for many generations and switching between them appears
      stochastic; however, environmental cues can significantly alter the frequency of
      switching. We review recent work on white-opaque switching, including the
      establishment of the transcriptional circuit underlying this switch, the
      identification of environmental signals that affect switching rates, newly
      discovered differences between the two types of cells, and the involvement of
      white-opaque switching in biofilm formation. We also review recent speculation on
      the evolution and adaptive value of white-opaque switching.

PMID- 19853500
TI  - Genetic code ambiguity: an unexpected source of proteome innovation and
      phenotypic diversity.
AB  - Translation of the genome into the proteome is a highly accurate biological
      process. However, the molecular mechanisms involved in protein synthesis are not
      error free and downstream protein quality control systems are needed to
      counteract the negative effects of translational errors (mistranslation) on
      proteome and cell homeostasis. This plus human and mice diseases caused by
      translational error generalized the idea that codon ambiguity is detrimental to
      life. Here we depart from this classical view of deleterious translational error
      and highlight how codon ambiguity can play important roles in the evolution of
      novel proteins. We also explain how tRNA mischarging can be relevant for the
      synthesis of functional proteomes, how codon ambiguity generates phenotypic and
      genetic diversity and how advantageous phenotypes can be selected, fixed, and
      inherited. A brief introduction to the molecular nature of translational error is
      provided; however, detailed information on the mechanistic aspects of
      mistranslation or comprehensive literature reviews of this topic should be
      obtained elsewhere.

PMID- 19853501
TI  - Comorbidity study of ADHD: applying association rule mining (ARM) to National
      Health Insurance Database of Taiwan.
AB  - OBJECTIVE: This paper intends to apply association rule mining (ARM) to explore
      the labyrinthian network of ADHD comorbidity, and to examine the practicality of
      ARM in comorbidity studies using clinic databases. METHODS: From clinic records
      of enrollees of Taiwan National Health Insurance (NHI), 18,321 youngsters aged 18
      or less with diagnosis of ADHD in 2001 were recruited as case group in this
      study. And all their clinic diagnoses made from 2000 to 2002, as comorbidity,
      were categorized according to "The International Classification of Disease, 9th
      Revision, Clinical Modification" (ICD-9-CM) diagnosis system. For comparison,
      fourfold non-ADHD controls were recruited from 2001s NHI enrollees on a random
      base but matched gender and age of cases. ARM was done with Apriori algorithm to
      examine the strengths of associations among those diagnoses. The support and
      confidence values of ARM results were examined. Comorbidity rates and relative
      risk (RR) ratios of both groups of each diagnosis were compared one another.
      RESULTS: ADHD case group has apparently higher risk of comorbidity with
      psychiatric comorbidity than with other physical illnesses. From results of ARM,
      developmental delay (DD) appears as an important node between ADHD and anxiety
      disorder (support: 5.12%, confidence: 97.42%), mild mental retardation (support:
      4.42%, confidence: 92.09%) and autism (support: 6.49%, confidence: 94.93%).
      CONCLUSIONS: The finding of this study, an important role of DD between ADHD and
      other psychiatric comorbidity, supports neurological findings in developmental
      delay of ADHD children's front cortex, as well as some epidemiology findings.
      This study also demonstrated the practicality of ARM in comorbidity studies using
      enormous clinic databases like NHIRD.

PMID- 19853502
TI  - Holes in the head.

PMID- 19853503
TI  - Put the right person in the right place: Segmental evaluation of the peripheral
      nerve for a diagnosis of CIDP.

PMID- 19853504
TI  - Homotopic long-term depression of trigeminal pain and blink reflex within one
      side of the human face.
AB  - OBJECTIVE: Electrical low-frequency stimulation (LFS) of cutaneous afferents
      elicits long-term depression (LTD) of craniofacial nociception and pain. The
      study addresses spatial organization of LTD within one side of the face. METHODS:
      The blink reflex was evoked by electrical test stimulation in the supraorbital
      nerve area before and after conditioning LFS in 10 healthy volunteers. Noxious
      LFS (1Hz) was applied to skin afferents of supraorbital (sLFS), infraorbital
      (iLFS), or mental (mLFS) nerves. All stimuli were applied to the same side of the
      face with intensities of three times pain threshold. Volunteers rated the test
      stimulus intensity. Each volunteer participated in four sessions with sLFS, iLFS,
      mLFS, or without LFS (control). RESULTS: Pain ratings of electrical test
      stimulation were differently affected in experimental sessions (p<0.01) with
      strongest reduction by -19.6% after sLFS. The reflex integral decreased by -34.7%
      significantly stronger after sLFS than in all other experimental conditions
      (p<0.001). Electrical pain thresholds increased significantly stronger in sLFS
      than in iLFS, mLFS, and control (p<0.001). CONCLUSIONS: Trigeminal nociception
      and pain were inhibited by homotopic LFS at the forehead but not after
      heterotopic LFS of infraorbital and mental nerve skin afferents. SIGNIFICANCE:
      Homotopic organization of ipsilateral trigeminal LTD in man may have implications
      for future neuromodulatory treatment of chronic craniofacial pain.

PMID- 19853505
TI  - The -174 G/C polymorphism of the IL6 gene is associated with elite power
      performance.
AB  - The -174 G/C polymorphism [rs1800795] of the IL6 gene is a candidate to explain
      individual variations in health and exercise related phenotypes. We compared -174
      G/C genotypic and allelic frequencies in three groups of men of the same
      Caucasian (Spanish) descent: elite endurance athletes (cyclists, runners; n=100);
      elite power athletes (jumpers, throwers, sprinters; n=53) and non-athletic
      controls (n=100). The frequency of the GG genotype (P=0.030) and G allele
      (P=0.026) was higher in the power athletes group compared with the control group.
      The frequency of the GG genotype (P=0.033) and G allele (P=0.013) was also higher
      in the power athletes group compared with the endurance athletes group. The odds
      ratio of being a power athlete if the subject had the GG genotype (dominant
      model) was 2.471 (95% confidence interval: 1.242-4.915) compared to the control
      group or the endurance athlete group. We did not find differences between the
      control and endurance athlete groups. In summary, our findings suggest that the G
      allele of the IL6 -174 G/C polymorphism might favour sprint/power sports
      performance.

PMID- 19853506
TI  - The acute effects of different whole-body vibration amplitudes and frequencies on
      flexibility and vertical jumping performance.
AB  - Frequency and amplitude determine the training load of whole-body vibration (WBV)
      exercise and thereby possible neuromuscular adaptations. We investigated the
      effects of amplitude and frequency of a single bout of WBV on flexibility and
      squat jump performance (SJ) and the time-course of these effects. In the
      amplitude study, twenty-five females performed three vibration protocols (VPs)
      for 6 min at frequency of 25Hz and amplitudes of 4 mm, 6 mm, and 8 mm and one
      control protocol (CP). In the frequency study, eighteen females performed three
      VPs at 6mm amplitude and frequencies of 15 Hz, 20 Hz, and 30 Hz and one CP.
      Flexibility and SJ were measured before, immediately-post and 15 min recovery.
      All protocols were performed on a side-to-side alternating vibration plate. In
      the amplitude study, flexibility was improved (p<0.01) immediately-post in VP4,
      VP6, VP8 (31.8+/-8.2, 31.9+/-7.6, 31.5+/-7.9, respectively) and at 15 min
      recovery (31.6+/-8.1, 31.5+/-7.9, 31.0+/-8.2, respectively) vs. pre-vibration
      (30.2+/-8.6, 30.3+/-8.1, 30.2+/-8.3, respectively), but remained unchanged in CP
      (30.6+/-8.3 immediately-post, 30.7+/-8.2 at 15 min vs. 30.4+/-8.2 pre-vibration).
      In the frequency study, flexibility was improved (p<0.01) immediately-post in
      VP15, VP20, VP30 (31.5+/-5.2, 31.3+/-5, 31.7+/-5.3, respectively) and at 15 min
      recovery (31.3+/-5.4, 31.3+/-5.0, 31.3+/-5.3, respectively) vs. pre-vibration
      (30.6+/-5.4, 30.2+/-5.7, 30.3+/-5.9, respectively), but not in CP (30.7+/-5.1
      immediately-post, 30.6+/-5 at 15 min vs. pre-vibration 30.5+/-5.7). There were no
      significant effects of amplitude or frequency on SJ. In conclusion, a single WBV
      bout using a side-to-side alternating vibration plate may increase flexibility
      which persists for at least 15 min, without altering jumping performance. These
      effects were observed irrespective of frequency and amplitude.

PMID- 19853507
TI  - Accuracy and reliability of GPS devices for measurement of movement patterns in
      confined spaces for court-based sports.
AB  - The aim of this study was to assess the accuracy and reliability of global
      positioning system (GPS) measures of distance and speed, compared to a high
      resolution motion analysis system, for confined movement patterns used in many
      court-based sports. A single male participant performed 10 repetitions of four
      respective drills replicating court-based movement patterns and six repetitions
      of a random movement drill that replicated tennis match-play movement patterns.
      Two 1Hz and two 5Hz GPS devices concurrently measured distance covered and speed
      of all court-based drills. A 22 camera VICON motion analysis system, operating at
      100Hz, tracked the position of an 18mm reflective marker affixed to one of the
      GPS devices to provide the criterion movement data. Results indicated that both 1
      and 5Hz GPS devices under reported distance covered as well as both mean and peak
      speed compared to the VICON system (P<0.05). The coefficient of variation for
      both GPS devices for distance and speed measures ranged between 4 and 25%.
      Further, the faster the speed and more repetitive the movement pattern (over a
      similar location), the greater the measurement error. The inter-unit reliability
      for distance and speed measures of both 1 and 5Hz systems for movements in
      confined spaces was generally low to moderate (r=0.10-0.70). In conclusion, for
      court-based sports or movements in confined spaces, GPS technology under reports
      distance covered and both mean and peak speed of movement.

PMID- 19853508
TI  - Match running performance in elite Australian Rules Football.
AB  - There is little information describing the match running demands of elite-level
      Australian Rules Football (AF). The aims of this study were to examine: (1) match
      running demands; and (2) the influence of periods of increased physical activity
      on subsequent running performance in the Australian Football League. Time-motion
      analyses were performed 1-9 times per player from 16 professional AF players from
      the same club during games in 2005-2007, using portable global positioning
      systems during 65 matches. Game movements (standing, walking, jogging, running,
      higher-speed running, and sprinting) and distances (total distance covered [TD];
      low-intensity activity [LIA, distance <14.4kmh(-1)]; and, high-intensity running
      distance [HIR, distance>14.4kmh(-1)]) were collected. The influence of the first
      half physical activities on second half activities, and each quarter on the
      subsequent quarter were analysed. The mean (+/-SD) TD and HIR distance covered
      during the games were 12,939+/-1145m and 3880+/-663m respectively. There were
      reductions in TD in the second (-7.3%), third (-5.5%) and fourth (-10.7%)
      quarters compared to the first quarter (p<0.01). The HIR was reduced after the
      first quarter (p<0.001). Players that covered larger TD or HIR during the first
      half or quarter decreased distance in the next half and quarter, respectively
      (p<0.001). These results show that a reduction in exercise intensity is
      inevitable during an AF match and that higher intensity activities reduce towards
      the end of games. High average speed during each half or quarter also affects
      subsequent running performance in elite-level AF.

PMID- 19853509
TI  - Epicardial cardiac basal annuloplasty: Preliminary findings on extra-cardiac
      mitral valve repair.
AB  - BACKGROUND: Correction of functional mitral regurgitation in ischaemic heart
      disease, with a better risk:benefit ratio is an unmet need. A new methodology of
      external approach of correcting the annulus (BACE: basal annuloplasty of the
      cardia externally) to repair and stabilise the mitral valve without entering the
      heart was used in this prospective study. This study was conducted to assess the
      efficacy and safety of the concept BACE device in patients with moderate
      functional mitral valve regurgitation as a result of symptomatic coronary artery
      disease and heart failure. METHODS: The study involved a group of patients who
      had complex cardiac surgery between January 2000 and December 2001 at the
      University of Melbourne Campus Hospitals, Melbourne, Australia. Twelve patients
      with ischaemic heart disease, congestive heart failure, and moderate functional
      mitral regurgitation (MR) (minimum 2+) underwent the BACE procedure along with
      coronary artery bypass grafting and/or left ventricular reconstruction. RESULTS:
      No peri-operative complications or deaths related to surgical procedures occurred
      in the study group. There were no clinically significant problems related to the
      BACE implantation procedure. Mean MR grade was significantly improved in BACE
      Group from baseline to post BACE implant (2.8 pre- and 0.3 post-surgery; P<0.05).
      Mean left ventricular ejection fraction (LVEF) was significantly improved
      (P<0.05) and maintained at 6, 12, and 18 months post BACE implant compared to pre
      operative baseline, with a mean improvement of 20% (24% at baseline to 44% at 18
      months post-operatively) (P<0.05). In addition to that the patients also had a
      significant improvement (P<0.05) in mean New York Heart Association (NYHA)
      functional status from pre-operative baseline to 6 and 18 months post procedure
      with BACE. CONCLUSIONS: External stabilisation of the cardiac base with BACE was
      associated with significant improvement in mitral valve function with no
      significant intra-operative or post-operative problems in patients with moderate
      functional MR. These findings support further study of BACE in functional MR.

PMID- 19853511
TI  - Towards a new standard of care for patients with myeloma?

PMID- 19853510
TI  - Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose
      dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open
      label randomised controlled trial.
AB  - BACKGROUND: High-dose dexamethasone is a mainstay of therapy for multiple
      myeloma. We studied whether low-dose dexamethasone in combination with
      lenalidomide is non-inferior to and has lower toxicity than high-dose
      dexamethasone plus lenalidomide. METHODS: Patients with untreated symptomatic
      myeloma were randomly assigned in this open-label non-inferiority trial to
      lenalidomide 25 mg on days 1-21 plus dexamethasone 40 mg on days 1-4, 9-12, and
      17-20 of a 28-day cycle (high dose), or lenalidomide given on the same schedule
      with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle (low dose).
      After four cycles, patients could discontinue therapy to pursue stem-cell
      transplantation or continue treatment until disease progression. The primary
      endpoint was response rate after four cycles assessed with European Group for
      Blood and Bone Marrow Transplant criteria. The non-inferiority margin was an
      absolute difference of 15% in response rate. Analysis was by modified intention
      to treat. This trial is registered with ClinicalTrials.gov, number NCT00098475.
      FINDINGS: 445 patients were randomly assigned: 223 to high-dose and 222 to low
      dose regimens. 169 (79%) of 214 patients receiving high-dose therapy and 142
      (68%) of 205 patients on low-dose therapy had complete or partial response within
      four cycles (odds ratio 1.75, 80% CI 1.30-2.32; p=0.008). However, at the second
      interim analysis at 1 year, overall survival was 96% (95% CI 94-99) in the low
      dose dexamethasone group compared with 87% (82-92) in the high-dose group
      (p=0.0002). As a result, the trial was stopped and patients on high-dose therapy
      were crossed over to low-dose therapy. 117 patients (52%) on the high-dose
      regimen had grade three or worse toxic effects in the first 4 months, compared
      with 76 (35%) of the 220 on the low-dose regimen for whom toxicity data were
      available (p=0.0001), 12 of 222 on high dose and one of 220 on low-dose
      dexamethasone died in the first 4 months (p=0.003). The three most common grade
      three or higher toxicities were deep-vein thrombosis, 57 (26%) of 223 versus 27
      (12%) of 220 (p=0.0003); infections including pneumonia, 35 (16%) of 223 versus
      20 (9%) of 220 (p=0.04), and fatigue 33 (15%) of 223 versus 20 (9%) of 220
      (p=0.08), respectively. INTERPRETATION: Lenalidomide plus low-dose dexamethasone
      is associated with better short-term overall survival and with lower toxicity
      than lenalidomide plus high-dose dexamethasone in patients with newly diagnosed
      myeloma. FUNDING: National Cancer Institute, Rockville, MD, USA.

PMID- 19853512
TI  - Monocytes and gammadelta T cells: close encounters in microbial infection.
AB  - gammadelta T cells comprise an evolutionarily conserved yet poorly understood
      subset of T cells. Numerous features place these unconventional lymphocytes at
      the branching point between antigen-presenting cells and natural killer cells of
      the innate immune system and major-histocompatibility-complex-restricted
      alphabeta T cells of the adaptive immune system. We propose a role for human
      Vgamma9/Vdelta2 T cells in the generation of monocyte-derived inflammatory
      dendritic cells during infection. Our model incorporates the peculiar innate-like
      specificity of Vgamma9/Vdelta2 T cells for the microbial metabolite (E)-4-hydroxy
      3-methyl-but-2-enyl pyrophosphate (HMB-PP), co-recruitment of monocytes and
      Vgamma9/Vdelta2 T cells to sites of infection, and their crosstalk, with profound
      consequences for the initiation of antigen-specific alphabeta T-cell responses.
      Vgamma9/Vdelta2 T cells act thus as a cellular switch between innate and adaptive
      defence mechanisms.

PMID- 19853513
TI  - Focusing on complement in the antiparasitic defense of mosquitoes.
AB  - Malaria is an infectious disease caused by Plasmodium and transmitted to humans
      by the Anopheles mosquitoes. The mosquito immune system predominantly targets
      Plasmodium at the ookinete stage, and efficiently eliminates the majority of
      invading parasites. Identification of the components of the mosquito complement
      system now provides new focus for studies on the activation and control of this
      pathway, whose manipulation is expected to block malaria transmission at the
      vector level.

PMID- 19853514
TI  - Efficiency analysis of KNN and minimum distance-based classifiers in enzyme
      family prediction.
AB  - Nearly all enzymes are proteins. They are the biological catalysts that
      accelerate the function of cellular reactions. Because of different
      characteristics of reaction tasks, they split into six classes: oxidoreductases
      (EC-1), transferases (EC-2), hydrolases (EC-3), lyases (EC-4), isomerases (EC-5),
      ligases (EC-6). Prediction of enzyme classes is of great importance in
      identifying which enzyme class is a member of a protein. Since the enzyme
      sequences increase day by day, contrary to experimental analysis in prediction of
      enzyme classes for a newly found enzyme sequence, providing from data mining
      techniques becomes very useful and time-saving. In this paper, two kinds of
      simple minimum distance-based classifier methods have been proposed. These
      methods and known K-nearest neighbor (KNN) classification algorithm have been
      performed in order to classify enzymes according to their amino acid composition.
      Performance measurements and elapsed time to execute algorithms have been
      compared. In addition, equality of two proposed approaches under special
      condition has been proved in order to be a guide for researchers.

PMID- 19853515
TI  - Orthotopic and heterotopic ovarian tissue transplantation.
AB  - Although still experimental, cryopreservation and transplantation techniques for
      ovarian tissue have been well described, and a number of successful human
      pregnancies have occurred. Ovarian cryopreservation is the only fertility
      preservation procedure that can be offered to prepubertal children, and when
      cytotoxic treatment is urgent. There are two main approaches for
      autotransplantation of human ovarian tissue. In the heterotopic transplantation,
      cortical fragments can be grafted subcutaneously at various sites whereas in
      orthotopic transplantation cortical pieces are transplanted into its original
      location. Both approaches have their own advantages and disadvantages. While
      natural pregnancy can occur in orthotopic transplantation, heterotopic
      transplantation may be indicated if the pelvis is not suitable for
      transplantation due to previous radiation or severe scar formation. Furthermore,
      tissue monitoring may be easier in the heterotopic site. In this article, we
      reviewed the indications, limitations, risks and transplantation techniques for
      ovarian tissue.

PMID- 19853517
TI  - Should patients with psychogenic nonepileptic seizures be allowed to drive?
      Recommendations of German experts.
AB  - In the absence of evidence-based regulations on the driving ability of patients
      with psychogenic nonepileptic seizures (PNES), we asked 41 German epileptologists
      via e-mail for their recommendations on driving with PNES. This survey was
      modeled on an earlier study by Benbadis et al. in the United States and was
      compared with it. Thirty-four (82.9%) epileptologists responded. Three responses
      were possible: (A) same restrictions as stipulated for patients with epilepsy,
      answered by 11 epileptologists (32.4%); (B) no restrictions at all, which no
      German expert gave as an answer (0%); (C) decision on an individual basis,
      answered by 23 experts (67.6%). The divergent approaches reflect the poor data on
      motor vehicle accidents of patients with PNES and the great variability of PNES
      with respect to semiology, psychiatric morbidity, and prognosis. In the study by
      Benbadis et al., 49% chose A, 32% B, and 19% C. The considerable national
      differences may be explained by differences between the two countries with
      respect to driving regulations and cultural aspects.

PMID- 19853516
TI  - From Galapagos to the labs: Darwinian medicine and epilepsy today.
AB  - In 1991, a mummy frozen in ice was found by climbers in the Tyrolean Alps. Otzi
      the Iceman has since been studied in the light of evolutionary explanations for
      diseases. This year, which marks Charles Darwin's 200th birthday and the 150th
      anniversary of his publication On the Origin of Species, should re-ignite
      discussion of the importance of the correlation between nutritional diet and
      diseases. Epilepsy is one of the commonest diseases in the world. Individuals
      with epilepsy are at higher risk of death than the general population, and sudden
      unexpected death (SUDEP) is the most important direct epilepsy-related cause of
      death. A number of factors may influence the risk for SUDEP. Along these lines,
      several studies have demonstrated that polyunsaturated (omega-3) fatty acids may
      reduce the risk of cardiovascular mortality, and diminish neuronal excitability.
      Also, omega-3 fatty acids may decrease seizure frequency, contributing to the
      reduction of SUDEP risk. Reconstruction of the nutritional patterns of Stone Age
      humans and optimal human nutrition in the present may be relevant to the
      prevention and treatment of chronic diseases such as epilepsy and the
      catastrophic evolution into epilepsy refractoriness and SUDEP.

PMID- 19853518
TI  - Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for
      cancer bone pain.
AB  - This multicenter study assessed the feasibility of conducting a phase III trial
      of transcutaneous electrical nerve stimulation (TENS) in patients with cancer
      bone pain recruited from palliative care services. Eligible patients received
      active and placebo TENS for 1 hour at site of pain in a randomized crossover
      design; median interval between applications 3 days. Responses assessed at 30 and
      60 minutes included numerical and verbal ratings of pain at rest and on movement,
      and pain relief. Recruitment, tolerability, adverse events, and effectiveness of
      blinding were also evaluated. Twenty-four patients were randomised and 19
      completed both applications. The intervention was well tolerated. Five patients
      withdrew: 3 due to deteriorating performance status, and 2 due to increased pain
      (1 each following active and placebo TENS). Confidence interval estimation around
      the differences in outcomes between active and placebo TENS suggests that TENS
      has the potential to decrease pain on movement more than pain on rest. Nine
      patients did not consider that a placebo was used; the remaining 10 correctly
      identified placebo TENS. Feasibility studies are important in palliative care
      prior to undertaking clinical trials. Our findings suggest that further work is
      required on recruitment strategies and refining the control arm before evaluating
      TENS in cancer bone pain. PERSPECTIVE: Cancer bone pain is common and severe, and
      partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous
      Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the
      feasibility of evaluating TENS in patients with cancer bone pain in order to
      optimize methods before a phase III trial.

PMID- 19853519
TI  - Predictability of painful stimulation modulates subjective and physiological
      responses.
AB  - Clinical observations suggest that the perceived intensity of a painful event
      increases as the unpredictability of its occurrence increases. We examined the
      effect of varying stimulus predictability on the Somatosensory Evoked Potential
      (SEP), Pupil Diameter Response (PDR), Pain Report (PR), and Fear Report (FR) in
      25 healthy female volunteers experiencing repeated noxious fingertip shocks. Each
      volunteer underwent high- and low-stimulus intensities in 4 stimulus patterns
      defined by stimulus sequence (SEQ) and interstimulus interval (ISI) as follows:
      A) serial stimulus intensity SEQ with fixed ISI; B) serial stimulus intensity SEQ
      with varied ISI; C) random stimulus intensity SEQ with fixed ISI; and D) random
      stimulus intensity SEQ with varied ISI. Results revealed that: (1) lower stimulus
      predictability led to higher PR and FR, greater PDR magnitude, and greater SEP
      amplitude; and (2) the 4 dependent measures showed the same response pattern
      across levels of stimulus predictability. These findings support the hypothesis
      that lower stimulus predictability is associated with higher reported pain and
      fear as well as greater physiological arousal. PERSPECTIVE: Patients undergoing
      painful procedures experience more distress when the occurrence of a painful
      event is unpredictable. Poor predictability increases pain, fear, and associated
      physiological arousal. Maximizing the predictability of painful events may
      improve the quality of patient care by minimizing associated levels of pain and
      fear.

PMID- 19853520
TI  - Differential roles of peripheral metabotropic glutamate receptors in bee venom
      induced nociception and inflammation in conscious rats.
AB  - Intraplantar injection of bee venom (BV) produces persistent spontaneous
      nociception (PSN), hyperalgesia, and inflammatory swelling of the injected paw.
      The present study was designed to determine the roles of peripheral metabotropic
      glutamate receptors (mGluRs) in BV-induced nociception and inflammation. We
      determined the effects of the group I mGluR antagonist AIDA, the group II mGluR
      agonist ADPC, and the group III mGluR agonist L-AP4 on BV-induced PSN, mechanical
      hyperalgesia, and inflammatory swelling. Pretreatment with intraplantar
      injections of AIDA, ADPC or L-AP4 at different doses significantly inhibited BV
      induced PSN over the 1-hour observational period. The inhibitory effects of ADPC
      and L-AP4 were completely abolished by pretreatment with the group II mGluR
      antagonist LY341495 and the group III mGluR antagonist MSOP, respectively.
      Pretreatment with ADPC prevented the BV-induced decrease in paw-withdrawal
      mechanical threshold (PWMT) in a dose-dependent manner, while pretreatment with
      AIDA or L-AP4 had no effect. The antihyperalgesic effect of ADPC was completely
      abolished by pretreatment with LY341495. Pretreatment with AIDA, ADPC or L-AP4 at
      different doses had no effect on the BV-induced increase in the paw volume (PV),
      a measurement of inflammatory swelling. All contralateral drug treatments at the
      highest doses had no effect on BV-induced PSN, decreases in PWMT or increases in
      PV, eliminating the possibility of drug-induced systemic effects. These data
      suggest that the activation of mGluRs in the periphery may play a differential
      role in BV-induced nociception and inflammation. PERSPECTIVE: The present study
      demonstrated that the intraplantar injection of antagonists or agonists of
      different mGluRs produced differential effects on bee venom-induced persistent
      spontaneous nociception and mechanical hyperalgesia. However, no effects on
      inflammation were observed, suggesting that mGluRs in the periphery have
      differential roles. Thus, therapies specifically targeting metabotropic glutamate
      receptors may improve the treatment of patients with persistent spontaneous
      nociception and hyperalgesia.

PMID- 19853522
TI  - Attachment and pain outcomes in adolescents: the mediating role of pain
      catastrophizing and anxiety.
AB  - This study examined the relations between attachment styles and pain
      severity/depression in adolescents. Analyses examined whether anxiety and the 3
      dimensions of pain catastrophizing mediated the associations between attachment
      styles, pain severity and depression. A total of 382 high-school students
      completed questionnaires assessing attachment styles, catastrophizing,
      depression, anxiety and, for those who reported pain during the last month, pain
      severity. Results revealed that secure attachment was associated with lower
      levels of pain severity, depression, pain catastrophizing and anxiety.
      Preoccupied and fearful attachment styles were associated with heightened pain
      severity, depression, pain catastrophizing and anxiety. Dismissing attachment
      style was only associated with high levels of depression and anxiety. Regression
      analyses revealed that anxiety and the helplessness dimension of pain
      catastrophizing mediated the relations between secure, preoccupied and fearful
      attachment styles and pain severity. Moreover, anxiety and the rumination
      dimension of pain catastrophizing mediated the relation between secure,
      preoccupied and fearful attachment styles and depression. These findings suggest
      that anxiety, pain catastrophizing and attachment styles are related processes
      but nevertheless make independent contributions to the prediction of pain
      severity and depression. In addition, these findings suggest that attachment
      styles and cognitive-affective factors might increase the risk of problematic
      outcomes in adolescents with pain conditions. Theoretical and clinical
      implications of these results are discussed. PERSPECTIVE: The results of this
      study revealed that anxiety and the helplessness dimension of pain
      catastrophizing mediated the relation between attachment and pain severity
      whereas anxiety and rumination mediated the relation between attachment and
      depression. Attachment style and cognitive-affective factors might increase
      vulnerability for problematic pain outcomes in adolescents.

PMID- 19853521
TI  - Pain catastrophizing and salivary cortisol responses to laboratory pain testing
      in temporomandibular disorder and healthy participants.
AB  - Pain catastrophizing is an important variable in the context of acute and chronic
      pain. The neurophysiological correlates of pain catastrophizing, however, have
      not been rigorously evaluated. We examined the relationship between trait-pain
      catastrophizing and morning salivary cortisol levels before and following a 45
      minute laboratory pain-testing session in healthy, pain-free (n = 22), and
      temporomandibular disorder (TMD) participants (n = 39). We also examined whether
      TMD patients evidenced generalized hyperalgesia and hypercortisolism. Pain
      catastrophizing was associated with a flattened morning salivary cortisol profile
      in the context of pain testing, irrespective of pain status. Cortisol profiles
      did not differ between healthy and TMD participants. TMD was associated with
      mechanical hyperalgesia only at the masseter. These data are the first to show an
      association between pain catastrophizing and elevated salivary cortisol profiles
      in the context of standardized experimental pain testing. These findings in both
      healthy individuals and those with chronic orofacial pain suggest that aberrant
      adrenocortical responses to pain may serve as a neurophysiologic pathway by which
      pain catastrophizing enhances vulnerability for development of chronic pain and
      maintains and/or exaggerates existing pain and associated morbidity. PERSPECTIVE:
      Neurophysiological mechanisms by which pain catastrophizing is related to acute
      and chronic pain recently have come under empirical study. Understanding of these
      mechanisms has the unique potential to shed light on key central-nervous-system
      factors that mediate catastrophizing-pain relations and therapeutic benefits
      associated with changes in catastrophizing and related cognitive processes.

PMID- 19853523
TI  - Interaction of morphine with a new alpha2-adrenoceptor agonist in mice.
AB  - Finding new chemicals or adjuvants with analgesic effects in the central nervous
      system is clinically relevant due to the limited number of drugs with these
      properties. Here, we present PT-31, which is chemically related to 3-benzyl
      imidazolidine, with an analgesic profile that results from alpha(2)-adrenoceptor
      activation. Intraperitoneal administration of PT-31 dose-dependently produced
      antinociception in the hot plate test, and interacted synergistically with
      morphine. This effect was completely reversed by yohimbine, a non-selective
      antagonist of alpha(2)-adrenoceptors, and by BRL 44408, a selective alpha(2A)
      adrenoceptor antagonist. The combination of morphine and PT-31 produced greater
      antinociceptive activity than either alone, and isobolographic analysis revealed
      a synergistic interaction between these compounds. Docking results confirm the
      high affinity of the PT-31 ligand at the alpha(2A)-adrenoceptor. PERSPECTIVE:
      This study introduces a new analgesic compound (PT-31) that acts via alpha(2A)
      adrenoceptor activation. A significant increase in analgesia was observed when co
      administered with morphine. PT-31 is an interesting new substance for pain
      therapy.

PMID- 19853524
TI  - Relationship of intersession variation in negative pain-related affect and
      responses to thermally-evoked pain.
AB  - The purpose of this study was to determine whether session-specific measures of
      negative pain-related affect would account for longitudinal variability in the
      ratings of the evoked thermal pain. Pain-free subjects rated pain evoked on the
      posterior leg using thermal stimuli of 45 degrees , 47 degrees , 49 degrees , and
      51 degrees C on 3 occasions, each separated by 2 weeks. Session-specific negative
      pain-related affect measures were also collected. Ratings of pain decreased
      significantly with repeated testing, demonstrating a systematic change in rating
      from the first to second sessions that ranged from a mean of 5.3 at 47 degrees C
      to 9.1 at 49 degrees C. In addition, large random variation occurred across all
      sessions, resulting in minimal detectable change ranging from 14 to 27. The least
      variability occurred when a mean rating of the 4 temperatures was used. Session
      specific measures of pain-related affect decreased with repeated testing;
      however, the significant between-subject variability in both rating of pain and
      pain-related affect were not related to each other. No associations were
      identified between psychological measures and variability in rating of evoked
      pain. Future studies of the variability in ratings should consider other factors
      such as attentional focus. PERSPECTIVE: The individual variability in thermal
      rating was not explained by individual variation in session-specific measures of
      negative pain-related affect. The results of this study support the use of
      repeated baseline measures of thermal stimuli when feasible. When this is not
      possible, the variability in ratings of thermal stimuli over multiple sessions is
      reduced when the mean of multiple temperatures is used.

PMID- 19853525
TI  - Activation of NMDA receptors in the brainstem, rostral ventromedial medulla, and
      nucleus reticularis gigantocellularis mediates mechanical hyperalgesia produced
      by repeated intramuscular injections of acidic saline in rats.
AB  - Repeated injections of acidic saline into the gastrocnemius muscle induce both
      muscle and cutaneous hypersensitivity. We have previously shown that
      microinjection of local anesthetic into either the rostral ventromedial medulla
      (RVM) or the nucleus reticularis gigantocellularis (NGC) reverses this muscle and
      cutaneous hypersensitivity. Although prior studies show that NMDA receptors in
      the RVM play a clear role in mediating visceral and inflammatory
      hypersensitivity, the role of NMDA receptors in the NGC or in noninflammatory
      muscle pain is unclear. Therefore, the present study evaluated involvement of the
      NMDA receptors in the RVM and NGC in muscle and cutaneous hypersensitivity
      induced by repeated intramuscular injections of acidic saline. Repeated
      intramuscular injections of acidic saline, 5 days apart, resulted in a bilateral
      decrease in the withdrawal thresholds of the paw and muscle in all groups 24
      hours after the second injection. Microinjection of NMDA receptor antagonists
      into the RVM reversed both the muscle and cutaneous hypersensitivity. However,
      microinjection of NMDA receptor antagonists into the NGC only reversed cutaneous
      but not muscle hypersensitivity. These results suggest that NMDA receptors in the
      RVM mediate both muscle and cutaneous hypersensitivity, but those in the NGC
      mediate only cutaneous hypersensitivity after muscle insult. PERSPECTIVE: The
      current study shows that NMDA receptors in supraspinal facilitatory sites
      maintain noninflammatory muscle pain. Clinical studies in people with chronic
      widespread, noninflammatory pain, similarly, show alterations in central
      excitability. Thus, understanding mechanisms in an animal model could lead to
      improved treatment for patients with chronic muscle pain.

PMID- 19853526
TI  - Sex differences and hormonal influences on response to mechanical pressure pain
      in humans.
AB  - Previous studies have demonstrated that sex differences in pain responsivity can
      be detected using various models of experimentally induced pain. The present
      study employed the mechanical pressure test in order to examine potential
      differences in pain report among men, normally menstruating women (NMW), and
      women taking monophasic oral contraceptives (OCW). Testing occurred during 5
      phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late
      luteal) and all participants completed 10 sessions (2 sessions per phase).
      Menstrual-cycle phase was estimated for OCW based on their first day of menses.
      Men were tested at time points that roughly corresponded to the intervals during
      which the different phases occurred in NMW. During the mechanical pressure test,
      4 different weights were placed on the fingers, one at a time, and ratings of
      pain were recorded for 30 seconds. The statistical decision-making model and a
      forced-choice procedure were used to analyze the response data. Two variables,
      based on signal detection theory, were thus generated: P(A), a measure of sensory
      pain, and B, a measure of response bias. P(A) is believed to be a measure of pain
      sensitivity while B measures stoicism. NMW tended to report lower P(A) values,
      indicating reduced ability to discriminate among different stimulus intensities,
      during the menstrual and late luteal phases compared to the luteal phase. OCW
      reported lower B values, indicating less stoicism, during the menstrual compared
      to the follicular and ovulatory phases. Men tended to have significantly lower B
      values than OCW, but not NMW. These results demonstrate subtle menstrual-cycle
      effects in NMW and OCW. Sex differences were few, with more group differences and
      trends emerging between OCW and men, as opposed to men and NMW. PERSPECTIVE: The
      lack of consistent differences between men and NMW underscores the subtle impact
      of sex and hormonal changes in pain report. In addition, the data obtained in NMW
      support the notion that changes in hormone levels during the menstrual cycle can
      lead to changes in pain responsivity as NMW had trends for better discrimination
      in menstrual phases when estradiol levels were highest.

PMID- 19853528
TI  - Increased risk of complex regional pain syndrome in siblings of patients?
AB  - An increased risk among siblings of probands with complex regional pain syndrome
      (CRPS) may be indicative of a genetic contribution. We calculated the sibling
      recurrence risk ratio (lambda(sibling)), a measure of familial aggregation. We
      surveyed 405 CRPS patients to collect information on the occurrence of CRPS in
      their siblings and compared this risk with the population risk to develop the
      syndrome. Information on disease status was collected from 1242 siblings, of
      which 24 were possibly affected according to their siblings. The diagnosis was
      confirmed in 16 patients, rejected in 2, and could not be verified in the
      remaining 6. Age-specific risk ratios were calculated for younger (<50 years) and
      older (> or =50 years) age groups. The strongest effects were seen in the younger
      age group, with a lambda(sibling) for possibly affected and confirmed cases of
      5.6 (95% CI, 3.0 to 9.8) and 3.4 (95% CI, 1.5 to 6.8), respectively. We concluded
      that this study yielded no indications for an overall increased risk of
      developing CRPS for siblings of CRPS patients but that the risk was significantly
      increased in siblings younger than 50, which may indicate that genetic factors
      play a more pronounced role in this subgroup. PERSPECTIVE: We studied the risk of
      developing CRPS for siblings of patients with this syndrome. Although the overall
      risk for siblings was not increased compared with the population risk, the risk
      for younger siblings was elevated. To enhance chances of success, future genetic
      studies may consider restricting inclusion to younger-onset cases.

PMID- 19853527
TI  - Race, care seeking, and utilization for chronic back and neck pain: population
      perspectives.
AB  - We analyzed a statewide survey of individuals with chronic back and neck pain to
      determine whether prevalence and care use varied by patient race or ethnicity. We
      conducted a telephone survey of a random sample of 5,357 North Carolina
      households in 2006. Adults with chronic (>3 months duration or >24 episodes of
      pain per year), impairing back or neck pain were identified and were asked to
      complete a survey about their health and care utilization. 837 respondents (620
      white, 183 black, 34 Latino) reported chronic back or neck pain. Whites and
      blacks had similar rates of chronic back pain. Back pain prevalence was lower in
      Latinos (10.4% [9.3-11.6] vs 6.3% [3.8-8.8]), likely due to their younger age;
      and the prevalence of chronic, disabling neck pain was lower in blacks (2.5% [1.9
      3.1] vs 1.1% [.04-1.9]). Blacks had higher pain scores in the previous 3 months
      (5.2 vs 5.9 P < .05), and higher Roland disability scores (0-23 point scale):
      14.2 vs 16.8, P < .05. Care seeking was similar among races (83% white, 85%
      black, 72% Latino). Use of opioids was also similar between races, at 49% for
      whites, 52% for blacks, and trended lower at 35% for Latinos. We found few
      racial/ethnic differences in care seeking, treatment use, and use of narcotics
      for the treatment of chronic back and neck pain. PERSPECTIVE: This article
      presents new, population-based data on the issue of racial and ethnic disparities
      in neck- and back-pain prevalence and care. Few disparities were found; care
      quality issues may affect all ethnic groups similarly. Previous findings of
      disparities in chronic-pain management may be decreasing, or may perhaps be site
      specific.

PMID- 19853529
TI  - Impact of postherpetic neuralgia and painful diabetic peripheral neuropathy on
      health care costs.
AB  - Knowledge of the health care costs associated with neuropathic pain is limited.
      Existing studies have not directly compared the health care costs of different
      neuropathic pain conditions, and patients with neuropathic pain have not been
      compared with control subjects with the same underlying conditions (for example,
      diabetes). To determine health care costs associated with postherpetic neuralgia
      (PHN) and painful diabetic peripheral neuropathy (DPN), patients with these
      conditions were selected from 2 different administrative databases of health care
      claims and respectively matched to control subjects who had a diagnosis of herpes
      zoster without persisting pain or a diagnosis of diabetes without neurological
      complications using propensity scores for demographic and clinical factors. Total
      excess health care costs attributable to PHN and painful DPN and excess costs for
      inpatient care, outpatient/professional services, and pharmacy expenses were
      calculated. The results indicated that the annual excess health care costs
      associated with peripheral neuropathic pain in patients of all ages range from
      approximately $1600 to $7000, depending on the specific pain condition. Total
      excess health care costs associated with painful DPN were substantially greater
      than those associated with PHN, which might reflect the great medical comorbidity
      associated with DPN. PERSPECTIVE: The data demonstrate that the health care costs
      associated with 1 peripheral neuropathic pain condition cannot be extrapolated to
      other neuropathic pain conditions. The results also increase understanding of the
      economic burden of PHN and painful DPN and provide a basis for evaluating the
      impact on health care costs of new interventions for their treatment and
      prevention.

PMID- 19853530
TI  - The effects of brief mindfulness meditation training on experimentally induced
      pain.
AB  - This study investigated the effects of brief mindfulness meditation training on
      ratings of painful electrical stimulation. In Experiment 1, we used a 3-day (20
      min/d) mindfulness meditation intervention and measured pain ratings before and
      after the intervention. Participants' numerical ratings of pain to "low" and
      "high" electrical stimulation significantly decreased after meditation training.
      Pain sensitivity, measured by change in stimulus intensity thresholds, also
      decreased after training. We investigated, in Experiment 2, how well relaxation
      and a math distraction task attenuated experimental pain. Math distraction but
      not relaxation reduced high pain ratings. There was no reduction in pain
      sensitivity in these participants. In Experiment 3, we directly compared the
      effects of meditation with math distraction and relaxation conditions. Our
      findings indicated significant effects of both meditation and math distraction.
      Consistent with what was observed in Experiment 1, these participants also
      demonstrated a decrease in pain sensitivity after meditation training. Changes in
      the mindfulness and anxiety assessments suggest that meditation's analgesic
      effects are related to reduced anxiety and the enhanced ability to focus on the
      present moment. PERSPECTIVE: Our findings indicate that a brief 3-day mindfulness
      meditation intervention was effective at reducing pain ratings and anxiety scores
      when compared with baseline testing and other cognitive manipulations. The brief
      meditation training was also effective at increasing mindfulness skills.

PMID- 19853531
TI  - Practical considerations for prostate HDR brachytherapy.
AB  - PURPOSE: A process for prostate high-dose-rate (HDR) brachytherapy was developed
      and implemented successfully in the community hospital setting. The practical
      aspects of the program are reviewed and may serve as a foundation for clinics
      interested in offering this clinical service. METHODS AND MATERIALS: A generic
      needle distribution geometry was established to accommodate target volumes of
      variable size. A system to identify and assign treatment channels to each implant
      needle was devised. The computerized tomography (CT)-based treatment planning was
      used with dose constraints defined for sensitive structures and target
      uniformity. Implant needle stability was promoted by supporting the patient on a
      CT compatible padded sliding board. A process that aligns dwell position to CT
      imaging without the use of radiographic markers was followed. Graphical
      optimization of dwell times was used to generate the treatment dose
      distributions. RESULTS: Prostate HDR brachytherapy as a boost or as monotherapy
      has been offered in a program that has evolved over the past 8 years. Practical
      aspects of the program promote its feasibility and precision. Collaboration with
      commercial entities has also led to the development of products that support the
      technique. CONCLUSIONS: Prostate HDR brachytherapy offers a relatively high
      degree of dose distribution control in comparison with other prostate
      radiotherapy modalities. The practical aspects described offer assurance to
      achieve that goal.

PMID- 19853532
TI  - Less-restrictive, patient-specific radiation safety precautions can be safely
      prescribed after permanent seed implantation.
AB  - PURPOSE: To use radiation exposure rate measurements to determine patient
      specific radiation safety instructions with the aim of reducing unnecessary
      precaution times and to evaluate potential doses to members of the public.
      METHODS AND MATERIALS: Radiation exposure rate measurements were obtained from
      1279 patients with Stage T1-2 prostate cancer who underwent transperineal (125)I
      or (103)Pd seed implantation from January 1995 through July 2008. An algorithm
      was developed from these measurements to determine the required precaution times
      to maintain public effective doses below 50% of the limits for specific exposure
      situations. RESULTS: The median air kerma rates at 30 cm from the anterior skin
      surface were 4.9 microGy/h (range: 0.1-31.5) for (125)I and 1.5 microGy/h (range:
      0.02-14.9) for (103)Pd. The derived algorithms depended primarily on the half
      life T(p), the measured exposure rate at 30 cm, and specific exposure situation
      factors. For the typical (103)Pd patient, no radiation safety precautions are
      required. For the typical (125)I patient, no precautions are required for
      coworkers, nonpregnant adults who do not sleep with the patient, or nonpregnant
      adults who sleep with the patient. Typical (125)I patients should only avoid
      sleeping in the "spoon" position (i.e., in contact) with pregnant adults and
      avoid holding a child for long periods of time in the lap for about 2 months.
      CONCLUSIONS: The large number of cases available for this study permitted the
      development of an algorithm to simply determine patient-specific radiation safety
      instructions. The resulting precaution times are significantly less restrictive
      than those generally prescribed currently.

PMID- 19853533
TI  - Late rectal toxicity after prostate brachytherapy: influence of supplemental
      external beam radiation on dose-volume histogram analysis.
AB  - PURPOSE: To describe the rate of gastrointestinal (GI) toxicity after prostate
      brachytherapy and describe how external beam radiation therapy (EBRT) may
      influence the association of rectal dose-volume histogram (DVH) parameters with
      rectal toxicity. METHODS AND MATERIALS: One hundred ten patients with prostate
      cancer were treated with I-125 brachytherapy alone (n=62, 144 Gy) or as a boost
      (n=48, 108 Gy) after 45-Gy EBRT. CT-based dosimetry was performed a median of 29
      days after implantation. GI toxicity was evaluated by Radiation Therapy Oncology
      Group criteria. Median followup was 41 months. RESULTS: Eleven patients developed
      Grade 2+GI toxicity. Men treated with EBRT had an increased risk of GI toxicity,
      with freedom from Grade 2+ toxicity of 82% vs. 91% for implant alone, but this
      difference was not statistically significant (p=0.3044). Of the DVH parameters
      analyzed, only the rectal volume receiving the prescription dose (rV(100)(%)) was
      associated with late Grade 2+GI toxicity. Men with rV(100%) >or= 0.05 cc had a 4
      year freedom from Grade 2+ toxicity of 77% vs. 100% for those with an rV(100%)
      <0.05 cc (p=0.0248). However, this relationship was only significant for the
      subset of patients treated with EBRT, where men with rV(100%) >or= 0.05 cc had a
      26% risk of Grade 2+ toxicity compared with 0% for rV(100%) <0.05 cc. Additional
      DVH parameters, including dose to the hottest 0.1 cc (p=0.0199), 1% (p=0.0086),
      and 3% (p=0.0043), were also associated with GI toxicity but only in men treated
      with EBRT. CONCLUSIONS: Supplemental EBRT may lower the threshold for rectal
      toxicity after prostate brachytherapy. Morbidity can be minimized by observing
      rectal constraints.

PMID- 19853534
TI  - Preliminary results in prostate cancer patients treated with high-dose-rate
      brachytherapy and intensity modulated radiation therapy (IMRT) vs. IMRT alone.
AB  - PURPOSE: To analyze results with high-dose-rate (HDR) brachytherapy and intensity
      modulated radiation therapy (IMRT) vs. IMRT alone for prostate cancer. METHODS
      AND MATERIALS: Between October 2003 and August 2008, 284 patients with early
      stage prostate cancer underwent HDR brachytherapy to 2200cGy and IMRT to 5040cGy
      (n=240) or IMRT alone to 7920-8100cGy (n=44). RESULTS: The median followup was
      2.2 years. There was no significant difference in terms of the proportions of
      patients who had diabetes mellitus (p=0.07) or who received hormonal therapy
      (p=0.75) by radiotherapy technique. The 3-year biochemical disease-free survival
      rates in low-risk, intermediate-risk, and high-risk patients treated with HDR
      brachytherapy and IMRT are 100%, 98%, and 93%, respectively. The 3-year
      biochemical disease-free survival rates in low-risk, intermediate-risk, and high
      risk patients treated with IMRT alone are 100%, 100%, and 67%, respectively.
      There was no significant difference in biochemical disease-free survival or
      toxicity between treatment groups. The similarity in outcomes between treatment
      groups remained unchanged when we examined only hormone-naive patients.
      CONCLUSIONS: The HDR brachytherapy and IMRT yielded similar biochemical disease
      free survival and toxicity to IMRT alone. As a result, we continue to base
      treatment on physician and patient preference. Longer followup will help to
      determine the role of HDR brachytherapy and IMRT in the treatment of early stage
      prostate cancer, particularly because a number of patients received androgen
      deprivation therapy and we delivered a higher biologically effective dose with
      combined modality therapy.

PMID- 19853535
TI  - Effect of planning margin on dosimetric quality in 131Cs permanent prostate
      brachytherapy.
AB  - PURPOSE: To investigate the dosimetric effect of planning margin in (131)Cs
      prostate seed implants. METHODS AND MATERIALS: The transrectal ultrasonography
      images are obtained intraoperatively in 5-mm steps from base to apex. The
      prostate is contoured as clinical target volume (CTV). The CTV is enlarged with
      3mm expansion except the posterior. The CTV and planning target volume (PTV) are
      then used as planning target for treatment planning, respectively. Dose
      calculations are performed using VariSeed treatment planning system using AAPM TG
      43 formalism. The total activity implanted, target coverage (the percent of the
      prostate volume covered by the prescription dose, V(100); the dose that covers
      90% of the prostate volume, D(90)) for CTV and PTV, dose inhomogeneity (the
      percentage volume of the prostate receiving 150% of the prescription dose
      [V(150)]), and the critical organ dose (the dose that covers 10% of the urethra
      volume [UD(10)] for urethra and the dose that covers 50% of the rectum volume
      [RD(50)] for rectum) are compared. RESULTS: When CTV is used as target for
      planning, compared with PTV as planning target, the total activity implanted is
      decreased by 5.6%. Integral dose is thus lower by 5.6%. Coverage for CTV
      (CTV(100)) is increased by 0.3%. Coverage for PTV (PTV(100)) is lower by 2.1%.
      CTV(150) is increased by 13.6%. PTV(150) is higher by 2.5% with a standard
      deviation of 10.2%. Rectum dose (RD(50)) is lower by 4.5%. Urethra dose (UD(10))
      is higher by 10.0%. CONCLUSION: It is shown that the planning margin has minimal
      effect on dosimetric quality because of (131)Cs's gradual dose fall-off. Thus, it
      is possible to reduce or even eliminate planning margin using (131)Cs. The modest
      benefits in reducing the planning margin, such as lower total activity (lower
      integral dose), dose reduction to surrounding healthy tissues and reduced
      likelihood of seeds migration, can be achieved while adequate coverage is
      maintained.

PMID- 19853536
TI  - 3D CT-based volumetric dose assessment of 2D plans using GEC-ESTRO guidelines for
      cervical cancer brachytherapy.
AB  - PURPOSE: To investigate two-dimensional (2D) radiograph-based plans using three
      dimensional (3D) dose-volume histogram (DVH) parameters following guidelines from
      Gynecologic GEC-ESTRO Working Group (GEC-ESTRO). METHODS AND MATERIALS: Nineteen
      high-dose-rate (HDR) fractions from 8 patients were studied. Prescription was 45
      Gy from external beam radiation therapy plus 30 Gy in five fractions from HDR
      using tandem and ring/ovoids. Both radiographs and CT scan were obtained.
      Treatment was planned using radiographs following American Brachytherapy Society
      (ABS) guidelines. Retrospective evaluation of above 2D plans on a 3D volumetric
      basis was achieved by generating CT image-based 3D plans using same dwell times.
      RESULTS: In 2D plans, International Commission on Radiation Units and Measurement
      (ICRU) bladder and rectal point doses were 3.8+/-0.4 and 3.0+/-0.5 Gy,
      respectively. In 3D plans, rectum D(2 cc) is 4.0+/-1.0 Gy and bladder D(2 cc) is
      5.4+/-0.9 Gy. Position of actual hottest spot in 3D rectum volume was close to
      the position of ICRU rectal point. ICRU bladder point did not match with the
      actual hottest spot in 3D bladder volume. In 2D plans, H-point dose was 5.8+/-0.2
      Gy. In 3D plans, dose to CT-based cervix (D(90)) reduced from 7.1 to 4.2 Gy as
      the cervical volume increased from 12 to 39 cc. Average D(2 cc)/ICRU dose ratio
      was calculated to be 1.36/1.01 for bladder/rectum, respectively. CONCLUSIONS: The
      DVH analysis of 2D plans revealed a suboptimal coverage of CT-based cervix and a
      negative correlation between coverage and cervical size. Rectum dose to 2 cc
      weakly correlated with ICRU point dose. Currently published constraint for
      bladder in 3D planning is tighter than ABS guidelines in past 2D planning.

PMID- 19853537
TI  - Intraoperative placement of MammoSite for breast brachytherapy treatment and
      seroma incidence.
AB  - PURPOSE: To identify possible risk factors for development of clinically
      significant seroma (CSS) (seroma requiring intervention) and to report on
      incidence of infection after intraoperative placement of MammoSite for breast
      brachytherapy. METHODS AND MATERIALS: Fifty-eight postmenopausal patients with
      early stage breast cancer and no nodal metastases, treated with partial breast
      irradiation using the MammoSite catheter from June 2003 to November 2007 were
      analyzed retrospectively for CSS predictive factors and incidence of infection.
      After a lumpectomy, a MammoSite catheter was placed by intraoperative open-cavity
      technique (OCT). All the patients received wound care and prophylactic
      antibiotics. A dose of 3400 cGy was prescribed at 1cm from the surface of the
      balloon and was delivered at 340 cGy twice daily 6h apart for 5 days. The
      patients with seroma who underwent intervention were considered to have CSS. On
      the basis of the characteristics and symptoms associated with seroma,
      interventions, such as aspiration, core biopsy, or re-excision of the lumpectomy
      cavity were performed either to relieve symptoms or to rule out a local
      recurrence. RESULTS: Fifty-seven of the 58 patients were eligible for analysis.
      One patient, who died 4 weeks after treatment from unrelated causes, was excluded
      from final analysis. All the patients were postmenopausal, with a median age of
      71 years (range, 53-88 years). Eighteen of the 57 patients (31.5%) had CSS; 9 of
      them had re-excision of the lumpectomy cavity. Pathology in all revealed evidence
      of fat necrosis, chronic inflammatory cells, and fibrosis. There was no evidence
      of tumor recurrence in any of these patients. Technical and nontechnical
      parameters were analyzed to determine possible risk factors for CSS, and none
      were found to be statistically significant. No patient developed acute
      postprocedural infection. CONCLUSIONS: Meticulous wound care and postoperative
      antibiotics prevented acute infection. Infection was not a contributing factor
      for seroma formation in these patients. Placement of the MammoSite catheter by
      OCT did not increase the risk of CSS development, in postmenopausal breast cancer
      patients.

PMID- 19853538
TI  - Periauricular mold brachytherapy.
AB  - PURPOSE: We present a patient with recurrent basal cell carcinoma (BCCA) who was
      treated with custom-made mold brachytherapy. METHODS AND MATERIALS: The patient
      was admitted to the hospital with the complaint of recurrent BCCA of the auditory
      canal. He has previously treated by surgery and external beam radiotherapy. We
      decided to continue with reirradiation to tumor bed after surgical excision. A
      total of 25 Gy to 5mm depth of surgical bed was delivered by mold brachytherapy.
      RESULTS: The patient did well during the treatment without any acute toxicity. He
      was lost to followup after 2 years of treatment without any obvious late
      morbidity. CONCLUSION: Custom-made mold brachytherapy is an alternative treatment
      modality, for reirradiation of selected group of patients, with minimal morbidity
      and good disease control.

PMID- 19853539
TI  - Comment on: Rationale for reversal of failed bariatric operations.

PMID- 19853540
TI  - Penetration of cefuroxime in subcutaneous tissue during coronary artery bypass
      grafting surgery.
AB  - A sensitive and rapid HPLC assay for determining cefuroxime penetration in the
      subcutaneous tissue near to surgical incision of patients submitted to coronary
      artery bypass grafting (CABG) with or without cardiopulmonary bypass (CPB) was
      performed. Blood and subcutaneous tissue samples were collected from 14 patients,
      in four periods during surgery. The analytical method presented linearity from
      0.5 to 100 microg/g, LOQ=0.50 microg/g, LOD=0.25 microg/g, intra- and interday
      precision (%CV) ranged from 4.9 to 8.9% and 6.4 to 9.9%, respectively, and intra-
      and interday accuracy expressed as % of the nominal concentration ranged from
      87.1 to 104.6% and 94.8 to 103.8%, respectively (mean of three concentrations).
      Relative recovery was 98.4%. Tissue/plasma ratios obtained for CPB and non-CPB
      were, respectively: 14.6% vs 19.0% (0.6 h); 15.7% vs 15.7% (2.1 h); 22.5% vs
      19.9% (3.6 h); 15.7% vs 18.8% (4.5 h). Data obtained indicate that tissue/plasma
      ratio remains unchanged in CPB and non-CPB patients during all period of surgery
      and the CPB does not affect the penetration of cefuroxime in tissues close to the
      surgical wound.

PMID- 19853541
TI  - A single LC-tandem mass spectrometry method for the simultaneous determination of
      four H2 antagonists in human plasma.
AB  - A sensitive and universal LC-MS/MS method for the simultaneous determination of
      famotidine, cimetidine, ranitidine and lafutidine in human plasma was presented.
      This is the first single LC-MS/MS method reported for the simultaneous analysis
      of these four H(2) antagonists in human plasma. Following liquid-liquid
      extraction with ethyl acetate, the separation was performed on an Agilent Zorbax
      SB-CN (150 mm x 2.1mm I.D., 5 microm) column using a mobile phase consisted of
      methanol:20 mM ammonium acetate (55:45, v/v). The total run time was 7 min per
      sample. Quantification was performed by electrospray ionization-triple quadrupole
      mass spectrometry by selected reaction monitoring (SRM) detection in the positive
      mode. All calibration curves showed good linear regression (r(2)>0.99) from 0.5
      to 1000 ng/mL for famotidine and lafutidine, and 5-20,000 ng/mL for cimetidine
      and ranitidine. The method showed good precision and accuracy with overall intra-
      and inter-day variations of 1.37-9.29% and 3.51-9.40%, respectively. The assay
      was successfully applied to a bioequivalence study using ranitidine as the model
      compound.

PMID- 19853542
TI  - Height and body mass index values of nineteenth-century New York legislators.
AB  - Previous studies of mid-nineteenth-century American BMI values have used data
      created by military academies and penitentiaries. This paper uses an alternative
      data set, constructed from legislative documents in which the heights and weights
      of New York State legislators were recorded. The results reveal that middle- to
      upper-middle class Americans maintained BMI values closer to the modern standard
      than did students and prisoners. The average BMI value among this group was 24
      and their height-weight combinations did not greatly diverge from historical
      mortality risk optima.

PMID- 19853543
TI  - [Long standing intestinal disorder as a form of presentation of
      spondylodiscitis].

PMID- 19853544
TI  - Effects of maternal obesity on fetal growth and body composition: implications
      for programming and future health.
AB  - Since the hypothesis linking low birth weight and poor fetal growth with future
      risk of cardiovascular disease was first proposed, there has been much interest
      in the early origins of disease. As rates of obesity increase and as maternal
      obesity has become common, interest has been directed towards the early origins
      of obesity. It is likely that a complex interaction of inherited gene effects and
      in-utero environment may interact in the developing fetus to programme pathways
      leading to future obesity. It is clear that maternal metabolism is disturbed in
      pregnancy in obese women, and that offspring of obese mothers have a higher
      percentage of body fat and are insulin resistant. This review discusses the ideas
      contributing to the current working concept of obesity programming, and discusses
      several potential mechanisms that may underlie obesity programming and
      susceptibility to future metabolic and vascular disease.

PMID- 19853545
TI  - Quilting of full thickness grafts in the hand.
AB  - A skin graft is the simplest way to reconstruct an area of skin loss. To improve
      the chance of successful take, shearing forces and haematoma formation between
      the bed and the graft must be reduced. To achieve this, many surgeons use a tie
      over dressing to secure the graft. However, 'quilting' the graft to the wound bed
      is an alternative method for securing grafts which may be superior to tie-over
      dressings. The purpose of this study was to compare the outcome of securing a
      full thickness graft by tie-over dressing versus quilting in the hand. To do
      this, we performed a retrospective review of graft-take in a consecutive series
      of 40 patients undergoing dermofasciectomy for Dupuytren's disease over a five
      year period. Our results demonstrate no significant difference in graft-take
      comparing grafts secured with a tie-over dressing or by quilting. Importantly,
      there were no cases of injury to the tendons or neurovascular structures in those
      cases where the graft was secured by quilting. Our technique for securing the
      graft by quilting is less time-consuming compared with a tie-over dressing.
      Therefore, we no longer use tie-over dressings to secure full-thickness grafts in
      the hand.

PMID- 19853546
TI  - Safety in the operating room: are we neglecting ourselves?

PMID- 19853548
TI  - [Prevalence and determinants of microalbuminuria and macroalbuminuria in children
      and young adults with type 1 diabetes in Kinshasa].
AB  - AIM: To determine the prevalence and determinants of microalbuminuria and
      macroalbuminuria in type 1 Congolese diabetics aged less than 30 years. METHODS:
      Cross sectional study (june-july 2008) at the Primary Health Care Center Boyambi
      in Kinshasa, The Democratic Republic of the Congo. HbA(1c) and urine albumin
      excretion (UAE) were measured by an enzyme immunoassay method. Determinants of
      microalbuminuria and macroalbuminuria were assessed by logistic regression.
      RESULTS: One hundred and eighty-one type 1 diabetics (female gender: 61.3%) were
      included in this study. They were aged 19.1+/-5.8 years and were diabetics for
      57.6+/-45.1 months. HbA(1c) was superior or equal to 10% in 88%, between 7 and
      10% in 4% and inferior to 7% in 8%. Prevalence of microalbuminuria and
      macroalbuminuria was 21.9% and 7.3%, respectively. Diabetes duration superior to
      5 years (OR: 4.1; 95% CI [1.9-8.4]), age superior to 18 years (OR: 2.9 [1.3-6.2])
      and HbA(1c) superior to 10% (OR: 2.6 [1.1-6.4]) were independent determinants of
      pathological UAE. CONCLUSION: Microalbuminuria and even macroalbuminuria are very
      frequent in type 1 Congolese diabetics aged above or equal to 30 years,
      especially in those aged above 18 years and diabetics for more than 5 years.
      Improving diabetes control and treating microalbuminuria is urgently needed to
      prevent renal insufficiency among children and young adults with type 1 diabetes
      of The Democratic Republic of the Congo.

PMID- 19853550
TI  - A life without teeth.

PMID- 19853551
TI  - Educating pediatricians and family physicians in children's oral health.
AB  - Publication of Oral Health in America: A Report of the Surgeon General (SGROH)
      alerted the public and health professionals to the importance of oral health and
      the vulnerability of poor and underserved children to dental disease. In
      response, the American Academy of Pediatrics (AAP), the American Academy of
      Family Physicians (AAFP), and the Society of Teachers of Family Medicine (STFM)
      have initiated training programs for residents and practicing physicians,
      allowing them to conduct oral health screenings, apply preventive strategies, and
      facilitate appropriate referrals to dentists. Training programs are increasingly
      available on the Web, but their quality and effectiveness are rarely assessed. To
      ensure greater inclusion of oral health in graduate medical education, voluntary
      curricular guidelines have been developed, and education in oral health is
      mandated in family medicine residency programs. Several initiatives engaging
      practicing physicians in oral health activities have demonstrated improved access
      and reduced dental disease in children, but evaluation of all programs is
      essential to determine cost effectiveness and outcomes. The actions of AAP, AAFP,
      STFM, and other large-scale initiatives have helped break down the traditional
      separation between medicine and dentistry. Collaboration between physicians and
      dentists should be encouraged at all levels of education to ensure improvement of
      the oral health of America's children.

PMID- 19853549
TI  - Lessons from development: A role for asymmetric stem cell division in cancer.
AB  - Asymmetric stem cell division has emerged as a major regulatory mechanism for
      physiologic control of stem cell numbers. Reinvigoration of the cancer stem cell
      theory suggests that tumorigenesis may be regulated by maintaining the balance
      between asymmetric and symmetric cell division. Therefore, mutations affecting
      this balance could result in aberrant expansion of stem cells. Although a number
      of molecules have been implicated in regulation of asymmetric stem cell division,
      here, we highlight known tumor suppressors with established roles in this
      process. While a subset of these tumor suppressors were originally defined in
      developmental contexts, recent investigations reveal they are also lost or
      mutated in human cancers. Mutations in tumor suppressors involved in asymmetric
      stem cell division provide mechanisms by which cancer stem cells can
      hyperproliferate and offer an intriguing new focus for understanding cancer
      biology. Our discussion of this emerging research area derives insight from a
      frontier area of basic science and links these discoveries to human
      tumorigenesis. This highlights an important new focus for understanding the
      mechanism underlying expansion of cancer stem cells in driving tumorigenesis.

PMID- 19853552
TI  - Adding dental therapists to the health care team to improve access to oral health
      care for children.
AB  - Oral Health in America: A Report of the Surgeon General, and the subsequent
      National Call to Action to Promote Oral Health, contributed significantly to
      raising awareness regarding the lack of access to oral health care by many
      Americans, especially minority and low-income populations, with resulting
      disparities in oral health. The problem is particularly acute among children. The
      current dental workforce in the United States is inadequate to meet the oral
      health care needs of children. It is inadequate in terms of numbers of dentists,
      as well as their geographic distribution, ethnicity, education, and practice
      orientation. Dental therapists, paraprofessionals trained in a 2 academic-year
      program of postsecondary education, have been employed internationally to improve
      access to oral health care for children. Research has documented that utilizing
      dental therapists is a cost-effective method of providing quality oral health
      care for children. Dental therapists have recently been introduced in Alaska by
      the Alaska Native Tribal Health Consortium. Dental therapists could potentially
      care for children in dental offices, public health clinics, and school systems,
      as well as in the offices of pediatricians and family physicians. Adding dental
      therapists to the health care team would be a significant strategy for improving
      access to care for children and reducing oral health disparities.

PMID- 19853547
TI  - [Mineral and bone status in French maintenance hemodialysis patients: a
      comparison of June 2005 and June 2008].
AB  - INTRODUCTION: Because of the high associated morbi-mortality, phosphate and
      calcium disorders remain a major therapeutic challenge for nephrologists.
      Previous studies showed that only few patients had serum calcium, phosphate and
      parathyroid hormone within Kidney-Disease Outcomes Quality Initiative (K/DOQI)
      targets. PATIENTS AND METHODS: The French calcium and phosphate observatory
      monitors mineral metabolism at local, regional and national level and its follow
      up every six months since 2005. More than 200 nephrologists collected more than
      9000 patients' data. We compared the results recorded in June 2005 with those
      collected in June 2008. RESULTS: As compared with June 2005, in June 2008 fewer
      patients were hypercalcemic according to the K/DOQI targets (-26.2%, p<0.001) and
      hyperphosphatemic (-16.5%, p<0.001), more patients were hypocalcemic (+45.5%,
      p<0.001) and hypophosphatemic (+8.8%, p<0.02). A greater number of patients had
      elevated serum PTH above 300ng/l (+17.6%, p<0.001) and fewer had a PTH lower than
      150ng/l (-25.4%, p<0.001). Serum 25OH vitamin D level was 21.7+/-20.0microg/l in
      June 2008. Overall, 10.5% of patients met all three K/DOQI targets, an
      improvement compared with June 2005 (6.8%, p<0.001). Between 2005 and 2008,
      cinacalcet, lanthane carbonate and native vitamin D derivatives prescription
      increased whereas calcium-based phosphate binders, sevelamer-HCL and active
      vitamin D derivatives decreased. CONCLUSION: Despite a significant improvement
      between 2005 and 2008, only few patients reach the three K/DOQI targets (10.5%)
      in 2008. The prospective biannual follow-up during three years will allow us to
      identify the impact of different treatments on calcium and phosphate metabolic
      control and patient's survival.

PMID- 19853553
TI  - Cancer pattern and survival in a rural district in South India.
AB  - BACKGROUND: Cancer pattern data are rare and survival data are none from rural
      districts of India. METHODS: The Dindigul Ambilikkai Cancer Registry (DACR)
      covering rural population of 2 millions in Dindigul district, Tamil Nadu state,
      South India, registered 4516 incident cancers during 2003-2006 by active case
      finding from 102 data sources for studying incidence pattern, of which, 1045
      incident cancers registered in 2003 were followed up for estimating survival.
      House visits were undertaken annually for each registered case for data
      completion. Cancer pattern was described using average annual incidence rates and
      survival experience was expressed by computing observed survival by actuarial
      method and age-standardized relative survival (ASRS). RESULTS: The average annual
      age-standardized rate per 100,000 of all cancers together was higher among women
      (62.6) than men (51.9) in DACR. The most common cancers among men were stomach
      (5.6), mouth (4.2) and esophagus (3.7). Cervical cancer (22.1) was ranked at the
      top among women followed by breast (10.9) and ovary (3.3). DACR incidence rates
      were lesser by at least two folds and 5-year survival were on par or lower than
      Chennai metropolitan registry for most cancers. Five-year age-standardized
      relative survival (%) in DACR was as follows: all cancers (29%), larynx (48),
      mouth (42), breast/tongue (38) and cervix (37). CONCLUSION: Cancer incidence was
      significantly lower, cancer patterns were markedly different and population-based
      cancer survival was lower in rural areas than urban areas thus providing valuable
      leads in estimating realistic cancer burden and instituting cancer control
      programs in India.

PMID- 19853554
TI  - Incidence of extranodal non-Hodgkin lymphomas among whites, blacks, and
      Asians/Pacific Islanders in the United States: anatomic site and histology
      differences.
AB  - BACKGROUND: Extranodal non-Hodgkin lymphoma (NHL) accounts for much of the
      increase in NHL incidence in the past three decades in the United States, but its
      descriptive epidemiology is scarce in the literature. METHODS: Incidence data for
      the years 1999-2003 were from 38 population-based cancer registries, covering 82%
      of US population. We grouped anatomic sites of extranodal NHLs according to the
      Surveillance, Epidemiology, and End Results (SEER) site recodes, and histology
      subtypes according to the nested classification of lymphoid neoplasms developed
      by the Pathology Working Group of the International Lymphoma Epidemiology
      Consortium. RESULTS: Blacks and Asians/Pacific Islanders (APIs) experienced
      incidence rates about the same as or lower than whites' for B-cell extranodal NHL
      as a whole and most of its histologic subtypes. The significant exceptions are:
      API men had a 40% higher rate of marginal zone lymphoma (MZL) than white men, and
      API women had a 12% higher rate of diffuse large B-cell lymphoma (DLBCL) than
      white women. The rates of all T-cell extranodal NHLs combined and peripheral T
      cell lymphoma (PTCL) among black women exceeded those of white women by 46% and
      18%, respectively. Blacks also had higher rates of mycosis fungoides (MF) than
      whites (28% higher for men and 99% higher for women). The most common sites of
      extranodal NHL are stomach, skin, and oral cavity and pharynx. Compared with
      whites, blacks had either lower or similar incidence of NHL for all sites except
      skin for women while APIs had higher rates of NHL of the stomach, nose/nasal
      cavity/middle ear, colorectum (women only), and brain (men only). Age was
      associated with race- and sex-specific differences in histology-specific
      incidence rates. CONCLUSION: While blacks and APIs had lower or similar overall
      incidence rates for extranodal NHL, they experienced excessive rates in some
      subtypes. Blacks had higher rates of the two most common types of T-cell
      extranodal NHL and APIs had higher rate of the two common types of B-cell types
      than whites. Distinct race-specific patterns in histology- and site-specific
      incidence of extranodal NHL may implicate racial differences in risk factor
      exposure and/or genetic predisposition.

PMID- 19853555
TI  - More than a pipe dream: uncovering mechanisms of vascular lumen formation.
AB  - An unresolved question in vasculogenesis is how mammalian endothelial cells make
      lumens in developing vessels. In this issue of Developmental Cell, Strilic et al.
      present a comprehensive analysis of murine arterial lumen formation that defines
      cellular and molecular events required for lumen morphogenesis and argues against
      a previous paradigm of lumen formation.

PMID- 19853556
TI  - Microtubule length control, a team sport?
AB  - Kinesin-8 family members function in microtubule length control and exhibit
      highly processive plus-end directed motility in conjunction with microtubule
      dissassembly activity. In a recent issue of Cell, Varga and colleagues describe
      how these two activities may be used to simultaneously measure and adjust the
      length of cellular microtubules.

PMID- 19853557
TI  - More than patterning--Hox genes and the control of posterior axial elongation.
AB  - Hox genes are well known for their evolutionarily conserved role in patterning
      the body axis. Now, Young et al. in this issue of Developmental Cell present
      evidence that at least in mouse embryos Hox genes do more, namely controlling the
      process of axis formation itself.

PMID- 19853558
TI  - About combs, notches, and tumors: epigenetics meets signaling.
AB  - The identities of cells, determined by differential gene expression, are
      heritably maintained by the antagonistic functions of Polycomb group (PcG) and
      Trithorax group proteins. Two recent papers shed new light on tumor suppressive
      functions of PcG by reporting direct silencing of the Notch and JAK/STAT
      signaling pathways in Drosophila melanogaster.

PMID- 19853560
TI  - A role for C. elegans Eph RTK signaling in PTEN regulation.
AB  - PTEN is one of the most commonly lost tumor suppressors in human cancer and is
      known to inhibit insulin signaling. Eph receptor tyrosine kinases (RTKs) have
      also been implicated in cancer formation and progression, and they have diverse
      functions, including nervous and vascular system development. We show that in C.
      elegans, the VAB-1 Eph kinase domain physically interacts with and phosphorylates
      PTEN (DAF-18), diminishing its protein levels and function. vab-1 mutants show
      increased longevity and sensitivity to dauer conditions, consistent with
      increased DAF-18/PTEN activity and decreased insulin-like signaling. Moreover,
      daf-18 mutations suppress vab-1 oocyte maturation phenotypes independent of PI3K
      signaling. We also present evidence that DAF-18 has protein phosphatase activity
      to antagonize VAB-1 action. Possible implications for human cancers are
      discussed, based on the idea that mutually inhibitory interactions between PTEN
      and Eph RTKs may be conserved.

PMID- 19853559
TI  - Arrestin development: emerging roles for beta-arrestins in developmental
      signaling pathways.
AB  - Arrestins were identified as mediators of G protein-coupled receptor (GPCR)
      desensitization and endocytosis. However, it is now clear that they scaffold many
      intracellular signaling networks to modulate the strength and duration of
      signaling by diverse types of receptors--including those relevant to the
      Hedgehog, Wnt, Notch, and TGFbeta pathways--and downstream kinases such as the
      MAPK and Akt/PI3K cascades. The involvement of arrestins in many discrete
      developmental signaling events suggests an indispensable role for these
      multifaceted molecular scaffolds.

PMID- 19853561
TI  - The core protein of glypican Dally-like determines its biphasic activity in
      wingless morphogen signaling.
AB  - Dally-like (Dlp) is a glypican-type heparan sulfate proteoglycan (HSPG),
      containing a protein core and attached glycosaminoglycan (GAG) chains. In
      Drosophila wing discs, Dlp represses short-range Wingless (Wg) signaling, but
      activates long-range Wg signaling. Here, we show that Dlp core protein has
      similar biphasic activity as wild-type Dlp. Dlp core protein can interact with
      Wg; the GAG chains enhance this interaction. Importantly, we find that Dlp
      exhibits a biphasic response, regardless of whether its
      glycosylphosphatidylinositol linkage to the membrane can be cleaved. Rather, the
      transition from signaling activator to repressor is determined by the relative
      expression levels of Dlp and the Wg receptor, Frizzled (Fz) 2. Based on these
      data, we propose that the principal function of Dlp is to retain Wg on the cell
      surface. As such, it can either compete with the receptor or provide ligands to
      the receptor, depending on the ratios of Wg, Fz2, and Dlp.

PMID- 19853562
TI  - MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular
      gland branching morphogenesis.
AB  - Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs
      and their proteolytic products are not clearly understood. Here, we discover that
      decreasing MT-MMP activity during submandibular gland branching morphogenesis
      decreases proliferation and increases collagen IV and MT-MMP expression.
      Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and
      morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV,
      and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we
      demonstrate the presence of collagen IV NC1 domains in developing tissue.
      Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis
      after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression
      via beta1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2
      siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and
      Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP
      dependent release of bioactive NC1 domains from collagen IV is critical for
      integrating collagen IV synthesis and proteolysis with epithelial proliferation
      during branching morphogenesis.

PMID- 19853563
TI  - Latrophilin signaling links anterior-posterior tissue polarity and oriented cell
      divisions in the C. elegans embryo.
AB  - Understanding the mechanisms that coordinate the orientation of cell division
      planes during embryogenesis and morphogenesis is a fundamental problem in
      developmental biology. Here we show that the orphan receptor lat-1, a homolog of
      vertebrate latrophilins, plays an essential role in the establishment of tissue
      polarity in the C. elegans embryo. We provide evidence that lat-1 is required for
      the alignment of cell division planes to the anterior-posterior axis and acts in
      parallel to known polarity and morphogenesis signals. lat-1 is a member of the
      Adhesion-GPCR protein family and is structurally related to flamingo/CELSR, an
      essential component of the planar cell polarity pathway. We dissect the molecular
      requirements of lat-1 signaling and implicate lat-1 in an anterior-posterior
      tissue polarity pathway in the premorphogenesis stage of C. elegans development.

PMID- 19853564
TI  - The molecular basis of vascular lumen formation in the developing mouse aorta.
AB  - In vertebrates, endothelial cells (ECs) form blood vessels in every tissue. Here,
      we investigated vascular lumen formation in the developing aorta, the first and
      largest arterial blood vessel in all vertebrates. Comprehensive imaging,
      pharmacological manipulation, and genetic approaches reveal that, in mouse
      embryos, the aortic lumen develops extracellularly between adjacent ECs. We show
      that ECs adhere to each other, and that CD34-sialomucins, Moesin, F-actin, and
      non-muscle Myosin II localize at the endothelial cell-cell contact to define the
      luminal cell surface. Resultant changes in EC shape lead to lumen formation.
      Importantly, VE-Cadherin and VEGF-A act at different steps. VE-Cadherin is
      required for localizing CD34-sialomucins to the endothelial cell-cell contact, a
      prerequisite to Moesin and F-actin recruitment. In contrast, VEGF-A is required
      for F-actin-nm-Myosin II interactions and EC shape change. Based on these data,
      we propose a molecular mechanism of in vivo vascular lumen formation in
      developing blood vessels.

PMID- 19853565
TI  - Cdx and Hox genes differentially regulate posterior axial growth in mammalian
      embryos.
AB  - Hox and Cdx transcription factors regulate embryonic positional identities. Cdx
      mutant mice display posterior body truncations of the axial skeleton, neuraxis,
      and caudal urorectal structures. We show that trunk Hox genes stimulate axial
      extension, as they can largely rescue these Cdx mutant phenotypes. Conversely,
      posterior (paralog group 13) Hox genes can prematurely arrest posterior axial
      growth when precociously expressed. Our data suggest that the transition from
      trunk to tail Hox gene expression successively regulates the construction and
      termination of axial structures in the mouse embryo. Thus, Hox genes seem to
      differentially orchestrate posterior expansion of embryonic tissues during axial
      morphogenesis as an integral part of their function in specifying head-to-tail
      identity. In addition, we present evidence that Cdx and Hox transcription factors
      exert these effects by controlling Wnt signaling. Concomitant regulation of
      Cyp26a1 expression, restraining retinoic acid signaling away from the posterior
      growth zone, may likewise play a role in timing the trunk-tail transition.

PMID- 19853567
TI  - DNA damage checkpoint maintains CDH1 in an active state to inhibit anaphase
      progression.
AB  - DNA damage checkpoint prevents segregation of damaged chromosomes by imposing
      cell-cycle arrest. In budding yeast, Mec1, Chk1, and Rad53 (homologous to human
      ATM/ATR, Chk1, and Chk2 kinases, respectively) are among the main effectors of
      this pathway. The DNA damage checkpoint is thought to inhibit chromosome
      segregation by preventing separase-mediated cleavage of cohesins. Here, we
      describe a regulatory network that prevents segregation of damaged chromosomes by
      restricting spindle elongation and acts in parallel with inhibition of cohesin
      cleavage. This control circuit involves Rad53, polo kinase, the anaphase
      promoting complex activator Cdh1, and the bimC kinesin family proteins Cin8 and
      Kip1. The inhibition of polo kinase by Rad53-dependent phosphorylation prevents
      it from inactivating Cdh1. As a result, Cdh1 remains in a partially active state
      and limits Cin8 and Kip1 accumulation, thereby restraining spindle elongation.
      Hence, the DNA damage checkpoint suppresses both cohesin cleavage and spindle
      elongation to preserve chromosome stability.

PMID- 19853566
TI  - LRF is an essential downstream target of GATA1 in erythroid development and
      regulates BIM-dependent apoptosis.
AB  - GATA-1-dependent transcription is essential for erythroid differentiation and
      maturation. Suppression of programmed cell death is also thought to be critical
      for this process; however, the link between these two features of erythropoiesis
      has remained elusive. Here, we show that the POZ-Kruppel family transcription
      factor, LRF (also known as Zbtb7a/Pokemon), is a direct target of GATA1 and plays
      an essential antiapoptotic role during terminal erythroid differentiation. We
      find that loss of Lrf leads to lethal anemia in embryos, due to increased
      apoptosis of late-stage erythroblasts. This programmed cell death is Arf and p53
      independent and is instead mediated by upregulation of the proapoptotic factor
      Bim. We identify Lrf as a direct repressor of Bim transcription. In strong
      support of this mechanism, genetic Bim loss delays the lethality of Lrf-deficient
      embryos and rescues their anemia phenotype. Thus, our data define a key
      transcriptional cascade for effective erythropoiesis, whereby GATA-1 suppresses
      BIM-mediated apoptosis via LRF.

PMID- 19853568
TI  - A yeast killer toxin screen provides insights into a/b toxin entry, trafficking,
      and killing mechanisms.
AB  - Like Ricin, Shiga, and Cholera toxins, yeast K28 is an A/B toxin that depends on
      endocytosis and retrograde trafficking for toxicity. Knowledge of the specific
      proteins, lipids, and mechanisms required for trafficking and killing by these
      toxins remains incomplete. Since K28 is a model for clinically relevant toxins,
      we screened over 5000 yeast mutants, identifying 365 that affect K28 sensitivity.
      Hypersensitive mutants revealed cytoprotective pathways, including stress
      activated signaling and protein degradation. Resistant mutants clustered to
      endocytic, lipid organization, and cell wall biogenesis pathways. Furthermore,
      GPI anchors and transcriptional regulation are important for K28-cell binding.
      Strikingly, the AP2 complex, which in metazoans links endocytic cargo to the
      clathrin coat, but had no assigned function in yeast, was critical for K28
      toxicity. Yeast AP2 localizes to endocytic sites and has a cargo-specific
      function in K28 uptake. This comprehensive genetic analysis identified conserved
      processes important for A/B toxin trafficking and killing.

PMID- 19853569
TI  - Meis cofactors control HDAC and CBP accessibility at Hox-regulated promoters
      during zebrafish embryogenesis.
AB  - Hox proteins form complexes with Pbx and Meis cofactors to control gene
      expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated
      promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx,
      and Meis in zebrafish tissues where these promoters are active. Inhibition of
      Meis blocks gene expression and reduces AcH4 levels at these promoters,
      suggesting a role for Meis in maintaining AcH4. Within Hox transcription
      complexes, Meis binds directly to Pbx and we find that this binding displaces
      histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos.
      Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting
      HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis
      are constitutively active and recruit CBP to increase AcH4 levels. We conclude
      that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox
      regulated promoters.

PMID- 19853570
TI  - Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and
      mouse.
AB  - We present new approaches to cis-regulatory module (CRM) discovery in the common
      scenario where relevant transcription factors and/or motifs are unknown.
      Beginning with a small list of CRMs mediating a common gene expression pattern,
      we search genome-wide for CRMs with similar functionality, using new statistical
      scores and without requiring known motifs or accurate motif discovery. We cross
      validate our predictions on 31 regulatory networks in Drosophila and through
      correlations with gene expression data. Five predicted modules tested using an in
      vivo reporter gene assay all show tissue-specific regulatory activity. We also
      demonstrate our methods' ability to predict mammalian tissue-specific enhancers.
      Finally, we predict human CRMs that regulate early blood and cardiovascular
      development. In vivo transgenic mouse analysis of two predicted CRMs demonstrates
      that both have appropriate enhancer activity. Overall, 7/7 predictions were
      validated successfully in vivo, demonstrating the effectiveness of our approach
      for insect and mammalian genomes.

PMID- 19853571
TI  - Vibrational spectroscopy and chemometrics to characterize and quantitate
      trehalose crystallization.
AB  - Investigating the phase behavior of sugars in ice and lyophilized solids is of
      significant interest in the pharmaceutical industry. In this study, Raman and
      near infrared (NIR) spectroscopy are used to characterize and quantitate
      trehalose crystallization using several chemometric models. The predictive
      behaviors of partial least squares (PLS), principal component analysis (PCA), and
      multiple linear regression (MLR) models are compared. In general, PLS and PCA
      outperform linear and MLR models. Changes in specific vibrational modes
      associated with several coupled motions are described and assigned as a function
      of crystal content. In addition to characterization and quantitation, our method
      may be used to localize gradients of amorphous and/or crystallized trehalose
      within a sample.

PMID- 19853572
TI  - HflD, an Escherichia coli protein involved in the lambda lysis-lysogeny switch,
      impairs transcription activation by lambdaCII.
AB  - The CII protein of bacteriophage lambda is the key regulator for the lytic
      lysogenic choice of the viral lifecycle. An unstable homotetrameric transcription
      activator of the three phage promoters p(E), p(I) and p(aQ), lambdaCII is
      stabilized by lambdaCIII and destabilized by the host protease, Escherichia coli
      HflB (FtsH). In addition, other E. coli proteins HflK, HflC and HflD also
      influence lysogeny by acting upon CII. Among these, HflD (22.9kDa), a peripheral
      membrane protein that is exposed towards the cytoplasm, interacts with CII and
      decreases the frequency of lysogenization of lambda by stimulating the
      degradation of CII. In this study, we show that in addition to helping CII
      degradation, HflD inhibits the DNA binding by CII, thereby inhibiting CII
      dependent transcription activation. From biochemical, biophysical and modelling
      studies we also suggest that HflD-CII interaction takes place through the Cys31
      accessible surface area of monomeric HflD, which binds to tetrameric CII as a 1:1
      complex.

PMID- 19853573
TI  - A new Factor Xa inhibitor from Amblyomma cajennense with a unique domain
      composition.
AB  - Bioactive compounds of great interest are found in the saliva of hematophagous
      organisms. While exploring a cDNA library derived from the salivary glands of the
      tick Amblyomma cajennense, a transcript that codes for a protein with unique
      structure (containing an N-terminal Kunitz-type domain and a C-terminus with no
      homology to any annotated sequences) was found. The recombinant mature form of
      this protein ( approximately 13.5kDa) was produced in Escherichia coli BL21
      (DE3), and it was able to inhibit Factor Xa (FXa) and extend global blood
      clotting times in vitro and ex vivo. Static and dynamic predictions of its
      tertiary structure indicate regions that may be related to its FXa inhibitor
      function.

PMID- 19853575
TI  - Quantum chemistry as a tool in bioenergetics.
AB  - Recent developments of quantum chemical methods have made it possible to tackle
      crucial questions in bioenergetics. The most important systems, cytochrome c
      oxidase in cellular respiration and photosystem II (PSII) in photosynthesis will
      here be used as examples to illustrate the power of the quantum chemical tools.
      One main contribution from quantum chemistry is to put mechanistic suggestions
      onto an energy scale. Accordingly, free energy profiles can be constructed both
      for reduction of molecular oxygen in cytochrome c oxidase and water oxidation in
      PSII, including O-O bond cleavage and formation, and also proton pumping in
      cytochrome c oxidase. For the construction of the energy diagrams, the
      computational results sometimes have to be combined with experimental
      information, such as reduction potentials and rate constants for individual steps
      in the reactions.

PMID- 19853574
TI  - Hydrodynamic and mass spectrometry analysis of nearly-intact human fibrinogen,
      chicken fibrinogen, and of a substantially monodisperse human fibrinogen fragment
      X.
AB  - The shape and solution properties of fibrinogen are affected by the location of
      the C-terminal portion of the Aalpha chains, which is presently still
      controversial. We have measured the hydrodynamic properties of a human fibrinogen
      fraction with these appendages mostly intact, of chicken fibrinogen, where they
      lack 11 characteristic 13-amino acids repeats, and of human fragment X, a plasmin
      early degradation product in which they have been removed. The human
      fibrinogen/fragment X samples were extensively characterized by SDS-PAGE/Western
      blotting and mass spectrometry, allowing their composition to be precisely
      determined. The solution properties of all samples were then investigated by
      analytical ultracentrifugation and size-exclusion HPLC coupled with multi-angle
      light scattering and differential pressure viscometry detectors. The measured
      parameters suggest that the extra repeats have little influence on the overall
      fibrinogen conformation, while a significant change is brought about by the
      removal of the C-terminal portion of the Aalpha chains beyond residue Aalpha200.

PMID- 19853576
TI  - Functional analysis of Photosystem I light-harvesting complexes (Lhca) gene
      products of Chlamydomonas reinhardtii.
AB  - The outer antenna system of Chlamydomonas reinhardtii Photosystem I is composed
      of nine gene products, but due to difficulty in purification their individual
      properties are not known. In this work, the functional properties of the nine
      Lhca antennas of Chlamydomonas, have been investigated upon expression of the
      apoproteins in bacteria and refolding in vitro of the pigment-protein complexes.
      It is shown that all Lhca complexes have a red-shifted fluorescence emission as
      compared to the antenna complexes of Photosystem II, similar to Lhca from higher
      plants, but less red-shifted. Three complexes, namely Lhca2, Lhca4 and Lhca9,
      exhibit emission maxima above 707 nm and all carry an asparagine as ligand for
      Chl 603. The comparison of the protein sequences and the
      biochemical/spectroscopic properties of the refolded Chlamydomonas complexes with
      those of the well-characterized Arabidopsis thaliana Lhcas shows that all the
      Chlamydomonas complexes have a chromophore organization similar to that of A.
      thaliana antennas, particularly to Lhca2, despite low sequence identity. All the
      major biochemical and spectroscopic properties of the Lhca complexes have been
      conserved through the evolution, including those involved in "red forms"
      absorption. It has been proposed that in Chlamydomonas PSI antenna size and
      polypeptide composition can be modulated in vivo depending on growth conditions,
      at variance as compared to higher plants. Thus, the different properties of the
      individual Lhca complexes can be functional to adapt the architecture of the PSI
      LHCI supercomplex to different environmental conditions.

PMID- 19853577
TI  - Structural and thermodynamic determinants of chain-melting transition
      temperatures for phospholipid and glycolipids membranes.
AB  - For optimum function, biological membranes need a fluid environment, which is
      afforded by the liquid-disordered phase of lipids with low chain-melting
      temperatures or the liquid-ordered phase that is formed by combining high chain
      melting lipids with cholesterol. The dependence of chain-melting transition
      temperature on lipid chain structure is therefore of central importance. The
      currently available database, including sphingolipids and glycolipids, is
      summarised here by parameterising systematic dependences on molecular structure
      in terms of suitable thermodynamic models. Chain-length dependence, chain
      asymmetry of lipids forming partially interdigitated and mixed interdigitated gel
      phases, chain unsaturation, positional dependence of methyl branching, headgroup
      attached and alpha-branched chains, and length of zwitterionic headgroups are all
      covered. This type of information is essential for biophysical approaches to
      functional lipidomics.

PMID- 19853578
TI  - Letter to the editor regarding recent retractions.

PMID- 19853579
TI  - Alzheimer's disease and Notch signaling.
AB  - Cleavage of the amyloid precursor protein (APP) by gamma-secretase generates a
      neurotoxic amyloid beta-peptide (Abeta) that is thought to be associated with the
      neurodegeneration observed in Alzheimer's disease (AD) patients. Presenilin is
      the catalytic member of the gamma-secretase proteolytic complex and mutations in
      presenilins are the major cause of early-onset familial Alzheimer's disease. In
      addition to APP, gamma-secretase substrates include Notch1 homologues, Notch
      ligands Delta and Jagged, and additional type I membrane proteins, raising
      concerns about mechanism-based toxicities that might arise as a consequence of
      inhibiting gamma-secretase. Notch signaling is involved in tumorigenesis as well
      as in determining the fates of neural and nonneural cells during development and
      in adults. Alterations in proteolysis of the Notch by gamma-secretase could be
      involved in the pathogenesis of AD. Inconsistently, several recent observations
      have indicated that enhanced Notch signaling and expression could be instrumental
      in neurodegeneration in AD. Therefore, detailed and precise study of Notch
      signaling in AD is important for elucidating diverse mechanisms of pathogenesis
      and potentially for treating and preventing Alzheimer's disease.

PMID- 19853580
TI  - Development of a functional in vitro integration system for an integral membrane
      protein, SecG.
AB  - A functional in vitro integration system for an integral membrane protein, SecG,
      comprising an efficient translation system supplemented with inverted membrane
      vesicles (IMV) was developed. When SecG was synthesized in the presence of IMV
      prepared from a DeltasecG strain (DeltaSecG IMV), the synthesized SecG was
      recovered with the IMV. A population of SecG was resistant to urea extraction,
      indicating that the synthesized SecG was integrated into DeltaSecG IMV. Addition
      of signal recognition particle and its receptor (SRP) and SecA caused an increase
      in the amount of the urea-resistant form of SecG. When IMV into which SecG had
      been integrated were subjected to the translocation assay, the translocation
      activity was found to be significantly stimulated compared with for DeltaSecG
      IMV. Moreover, when SRP and SecA had been supplemented, the translocation
      activity nearly recovered to the level in IMV prepared from the wild type strain.
      These results indicate that the in vitro synthesized SecG could be functionally
      integrated into DeltaSecG IMV with the help of SRP and SecA. We also present
      evidence that the membrane targeting and integration of SecG is stimulated by
      externally added SecA and SecG itself.

PMID- 19853581
TI  - Genomic structure and transcriptional regulation of grass carp calmodulin gene.
AB  - A fish calmodulin (CaM) gene was characterized for the first time in grass carp.
      The CaM gene is about 12-Kb in size with identical intron/exon organization as
      that of mammalian CaM genes. When compared to mammalian counterparts, the 5'
      promoter region of grass carp CaM gene contains a TATA box and has a much lower
      GC content and CpG dinucleotide frequency. Interestingly, the 5'-promoter of carp
      CaM gene is AT-rich with multiple IRS elements and putative binding sites for Pit
      1, Sp1/Sp3 and AP1. Using luciferase reporter assay, a potent silencer region was
      identified in the distal region of grass carp CaM promoter. Besides, the CaM
      promoter activity could be upregulated by IGF but suppressed by PACAP, forskolin
      and over-expression of Sp1 and Sp3. These findings, taken together, indicate that
      grass carp CaM gene does not exhibit the typical features of housekeeping genes
      and its expression is under the control of hormone factors, presumably by
      coupling with the appropriate signaling pathways/transcription factors.

PMID- 19853582
TI  - The conserved Trp155 in human frataxin as a hotspot for oxidative stress related
      chemical modifications.
AB  - Frataxin is a mitochondrial protein that is defective in Friedreich's ataxia
      resulting in iron accumulation and an environment prone to Fenton reactions. We
      report that frataxin is susceptible to carbonylation and nitration modifications
      in residues from the beta-sheet surface (Tyr143, Tyr174, Tyr205 and Trp155).
      Frataxin functions are not significantly affected: frataxin-mediated protection
      against ROS is still observed, as well as iron-binding (5 Fe(3+)mol(-1), K(d)
      from 13-36 microM) necessary for the metallochaperone activity. However, the
      protein is up to 1.0 kcal mol(-1) destabilized, with conformational opening.
      Interestingly, the strictly conserved Trp155, which is mutated in patients, may
      be a functional hotspot in frataxin.

PMID- 19853583
TI  - FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the
      repression of the ENT1 expression.
AB  - Fms-related tyrosine kinase 3-internal tandem duplications (FLT3-ITD) are
      strongly associated with the refractory nature of acute myeloid leukemia (AML) by
      the standard combined chemotherapy. FLT3-ITD-expressing murine and human myeloid
      cell lines, HF6/FLT3-ITD and K562/FLT3-ITD cells, respectively, were developed in
      order to clarify whether FLT3-ITD is involved in the resistance to cytotoxic
      agents in AML. Both of these cell lines were specifically resistant to the
      pyrimidine analogue cytosine arabinoside (ara-C), an essential agent for AML,
      accompanied by the downregulation of equilibrative nucleoside transporter 1
      (ENT1), a transporter responsible for the cellular uptake of ara-C. The ENT1
      promoter activity and the cellular uptake of ara-C were reduced in K562/FLT3-ITD
      cells, and rescued by pretreating the cells with PKC412, a FLT3 inhibitor. In
      addition, the expression of hypoxia inducible factor 1 alpha subunit (HIF1A)
      transcripts was upregulated in K562/FLT3-ITD cells, and the induction of HIF
      1alpha reduced the promoter activity of ENT1 gene in K562 cells. Taken together,
      these findings suggest that FLT3-ITD specifically induces ara-C resistance in
      leukemic cells by the repression of ENT1 expression, possibly through the
      upregulation of HIF-1alpha, while also partially accounting for the poor
      prognosis of AML with FLT3-ITD due to resistance to the standard chemotherapy
      protocols which include ara-C.

PMID- 19853584
TI  - Apoptosis induction with electric pulses - a new approach to cancer therapy with
      drug free.
AB  - Electrical pulses have been widely used in biomedical fields, whose applications
      depend on the parameters such as durations and electric intensity. Conventional
      electroporation (0.1-1kV/cm, 100micros) has been used in cell fusion,
      transfection and electrochemotherapy. Recent studies with high-intensity (MV/cm)
      electric field applications with durations of several tens of nanoseconds can
      affect intracellular signal transduction and intracellular structures with plasma
      intact, resulting in an application of intracellular manipulation. The most
      recent development is the finding that parameters between those two ranges could
      be used to induce apoptosis of cancer cells. Proposal of apoptosis induction and
      tumor inhibition has advantages to pursue the treatment of cancer free of
      cytotoxic drugs.

PMID- 19853585
TI  - Neural substrates of irony comprehension: A functional MRI study.
AB  - In daily communication, we sometimes use ironic expressions to convey the
      opposite meaning. To understand these contradictory statements, we have to infer
      contextual implications and the speaker's mental state. However, little is known
      about how our brains carry out these complex processes. In this study, we
      investigated the neural substrates involved in irony comprehension using echoic
      utterance (Sperber and Wilson, 1986, 1995). Participants read a short scenario
      that consisted of five sentences. The first four sentences explained the
      situation of the protagonists. The fifth connoted either an ironic, literal, or
      unconnected meaning. The participants had to press a button to indicate whether
      or not the final sentence expressed irony. In the ironic sentence condition, the
      bilateral superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus,
      medial prefrontal cortex, superior temporal gyrus, inferior parietal lobule,
      caudate, thalamus, the left insula, and amygdala were activated. In the literal
      sentence condition, the right superior frontal gyrus, the bilateral middle
      frontal gyrus, inferior frontal gyrus, medial prefrontal cortex, superior
      temporal gyrus, inferior parietal lobule, caudate, the left insula, the right
      thalamus, and the left amygdala were activated. However, in the ironic sentence
      condition minus the literal sentence condition, we observed higher activation in
      the right medial prefrontal cortex (BA 10), the right precentral (BA 6), and the
      left superior temporal sulcus (BA 21). Our results suggest that irony
      comprehension is strongly related to mentalizing processes and that activation in
      these regions might be affected by higher-order cognitive operations.

PMID- 19853586
TI  - Electrophysiological attention effects in a virtual cocktail-party setting.
AB  - The selection of one of two concurrent speech messages for comprehension was
      investigated in healthy young adults in two event-related potential experiments.
      The stories were presented from virtual locations located 30 degrees to the left
      and right azimuth by convolving the speech message by the appropriate head
      related transfer function determined for each individual participant. In
      addition, task irrelevant probe stimuli were presented in rapid sequence from the
      same virtual locations. In experiment 1, phoneme probes (/da/ voiced by the same
      talkers as attended and unattended messages) and band-pass filtered noise probes
      were presented. Phoneme probes coinciding with the attended message gave rise to
      a fronto-central negativity similar to the Nd-attention effect relative to the
      phoneme probes coinciding with the unattended speech message, whereas noise
      probes from the attended message's location showed a more positive frontal ERP
      response compared to probes from the unattended location resembling the so-called
      rejection positivity. In experiment 2, phoneme probes (as in exp. 1) and
      frequency-shifted (+400 Hz) were compared. The latter were characterized by a
      succession of negative and positive components that were modulated by location.
      The results suggest that at least two different neural mechanisms contribute to
      stream segregation in a cocktail-party setting: enhanced neural processing of
      stimuli matching the attended message closely (indexed by the Nd-effect) and
      rejection of stimuli that do not match the attended message at the attended
      location only (indexed by the rejection positivity).

PMID- 19853587
TI  - Protein 4.1 expression in the developing hair cells of the mouse inner ear.
AB  - Protein 4.1 (band 4.1 or 4.1R) was originally identified as an abundant protein
      of the human erythrocyte, in which it stabilizes the spectrin/actin cytoskeleton.
      Subsequently, several new family members, 4.1N, 4.1G and 4.1B, have been
      identified, which are expressed in many cell types, in particular at cell-cell
      junctions. We previously reported that 4.1R and 4.1N are expressed in the inner
      ear hair cells with specific localization patterns, and that 4.1R forms a complex
      with the membrane-associated guanylate kinase (MAGUK) protein p55 and two
      deafness gene products, myosin XV and whirlin. To determine the functions of the
      other family members, 4.1G and 4.1B, we observed their expression patterns in
      developing stereocilia in mice inner ear hair cells. 4.1G is expressed in the
      basal tapers of the stereocilia bundle in early postnatal stages. 4.1B was
      specifically and constantly expressed in the stereocilia tips during postnatal
      development. Additionally, we found that 4.1B is ablated in the hair cells of
      both myosin XV and whirlin mutant mice at all stages in hair cell development.
      These results suggest that 4.1 family members play important roles in the
      development and maintenance of the inner ear hair cells, and that 4.1B may be a
      member of the myosin XV-whirlin complex that is important for stereocilia
      maturation.

PMID- 19853588
TI  - 12/15-Lipoxygenase inhibitor baicalein suppresses PPAR gamma expression and
      nuclear translocation induced by cerebral ischemia/reperfusion.
AB  - Accumulating evidences have demonstrated the beneficial actions of peroxisome
      proliferator-activated receptor gamma (PPAR gamma) in a variety of animal stroke
      models. Following middle cerebral artery occlusion (60 min) and 2-24 hr
      reperfusion in rats, we observed cerebral ischemia/reperfusion (I/R) induced up
      regulation of PPAR gamma protein expression and translocation from the cytoplasm
      into the nucleus in a time-dependent manner. We also found that PPAR gamma
      agonist rosiglitazone enhanced whereas PPAR gamma antagonist GW9662 inhibited the
      alteration of PPAR gamma stimulated by I/R, suggesting that the changes of PPAR
      gamma may result from the activation by endogenous ligands. Moreover, the link
      between the 12/15-lipoxygenase and the production of activating ligands for PPAR
      gamma has been proved in various tissues. However, the relation of them in brain
      tissue has not been identified. We demonstrated that the I/R-induced PPAR gamma
      alteration was reversed by baicalein, the specific inhibitor of 12/15
      lipoxygenase. Baicalein treatment significantly inhibited the up-regulation of
      PPAR gamma expression and, furthermore, suppressed PPAR gamma nuclear
      accumulation as well as maintained PPAR gamma cytoplasmic retention. Together,
      these results suggest that I/R induces both PPAR gamma expression and
      translocation, probably through the activation by endogenous ligands in a 12/15
      lipoxygenase inhibitor-sensitive way.

PMID- 19853589
TI  - Retinal ganglion cell death induced by endoplasmic reticulum stress in a chronic
      glaucoma model.
AB  - This study investigated whether endoplasmic reticulum (ER) stress induced retinal
      ganglion cell (RGC) death in chronic ocular hypertension, one of the RGC death
      mechanisms, using an experimental glaucoma rat model. Glaucoma was induced in
      adult male Sprague-Dawley rats by cauterizing three episcleral veins. The
      intraocular pressure (IOP) remained elevated in the cauterized eyes for the 8
      week experiment, whereas it was not elevated in the contralateral control eyes.
      The average number of RGCs decreased significantly, and TUNEL-positive cells were
      detected in the ganglion cell layer. In western blotting, Bip, the phosphorylated
      form of PKR (p-PERK), and C/EBP-homologous protein (CHOP) were significantly
      expressed at 1 or 2 weeks, and this persisted throughout the 8-week experiment.
      Phosphorylated eukaryotic initiation factor 2 (p-eIF2alpha) began to increase at
      1 week, was sustained through 4 weeks, and decreased slightly at 8 weeks. In
      cauterized eyes, strong p-PERK and CHOP immunoreactivity was observed in ganglion
      cells after 8 weeks of IOP elevation. Taken together, in the experimental chronic
      glaucoma model, ER stress is involved in RGC death, and the PERK-p-eIF2alpha-CHOP
      pathway plays a role in the RGC apoptosis associated with ER stress. This might
      be a good therapeutic target to protect RGCs from ER stress injury in glaucoma.

PMID- 19853590
TI  - Motor area localization using fMRI-constrained cortical current density
      reconstruction of movement-related cortical potentials, a comparison with fMRI
      and TMS mapping.
AB  - The localization of human hand primary motor area (M1) has been the object of
      several studies during the last decades. EEG source analysis, functional magnetic
      resonance imaging (fMRI) and focal transcranial magnetic stimulation (TMS) are
      non-invasive methods for localizing M1 with good accuracy compared to direct
      electrocorticography (ECoG) results. EEG sources were reconstructed with Cortical
      Current Density (CCD) method, allowing to evaluate simultaneous and distributed
      patterns of activation and to increase accuracy by constraining on information
      derived from fMRI (fMRI-CCD). The aim of this study was to compare the M1
      contribution of movement-related cortical potentials (MRCP) with TMS and fMRI
      results and to test the effect of constraints strength, algorithm norm and
      localization methods over CCD reconstruction. Seven right-handed healthy subjects
      underwent 64-channel EEG recording of MRCP to right thumb movement, focal TMS
      mapping of the right abductor pollicis brevis muscle and fMRI during right hand
      movement. We found fMRI activations, EEG sources and TMS mapping corresponding to
      the anatomical landmark of the hand area in all subjects with fMRI and TMS center
      of-gravity and in almost all subjects using fMRI-CCD with moderate constraint. A
      significant improvement was found using fMRI-CCD compared to CCD alone. This
      study confirms the usefulness of multimodal integration of fMRI, EEG and TMS in
      localizing M1 and the possibility to increase EEG spatial resolution using fMRI
      information.

PMID- 19853591
TI  - Comparative study of the oxidation of propranolol enantiomers in hepatic and
      small intestinal microsomes from cynomolgus and marmoset monkeys.
AB  - Oxidative metabolism of propranolol (PL) enantiomers (R-PL and S-PL) to 4
      hydroxypropranolol (4-OH-PL), 5-OH-PL and N-deisopropylpropranolol (NDP) was
      examined in hepatic microsomes from cynomolgus and marmoset monkeys and in small
      intestinal microsomes from monkeys and humans. In hepatic microsomes, levels of
      oxidation activities were similar between the two monkey species, and substrate
      enantioselectivity (R-PL<S-PL) was observed in the formation of 5-OH-PL and/or
      NDP. Kinetic experiments revealed that the formation of all metabolites was
      biphasic in cynomolgus monkeys, whereas only the formation of NDP was biphasic in
      marmosets. Inhibition experiments employing human CYP antibodies and chemical
      inhibitors suggested that mainly CYP2D enzymes and partially CYP1A and 2C enzymes
      are involved in the oxidation of PL in both monkey liver microsomes. In small
      intestinal microsomes, activity levels were much higher in cynomolgus monkeys
      than in marmosets and humans and reversed substrate enantioselectivity (R-PL>S
      PL) was seen in the formation of NDP in cynomolgus monkeys and humans and in the
      formation of 5-OH-PL in marmosets. The formation of the three metabolites in
      cynomolgus monkeys and the formation of NDP in marmosets were biphasic, while the
      formation of 4-OH-PL in humans was monophasic. From the inhibition experiments
      using CYP antibodies, CYP2C9 and 2C19 were thought to be involved as N
      deisopropylases and CYP2D6 and 3A4 as 4-hydroxylases in human small intestine.
      Furthermore, CYP1A, 2C and 3A enzymes could be involved in cynomolgus monkeys and
      CYP2C and 3A enzymes in marmosets. These results indicate that the oxidative
      profile of PL in hepatic and small intestinal microsomes differ considerably
      among cynomolgus monkeys, marmosets and humans.

PMID- 19853592
TI  - Local anesthetics structure-dependently interact with anionic phospholipid
      membranes to modify the fluidity.
AB  - While bupivacaine is more cardiotoxic than other local anesthetics, the
      mechanistic background for different toxic effects remains unclear. Several
      cardiotoxic compounds act on lipid bilayers to change the physicochemical
      properties of membranes. We comparatively studied the interaction of local
      anesthetics with lipid membranous systems which might be related to their
      structure-selective cardiotoxicity. Amide local anesthetics (10-300 microM) were
      reacted with unilamellar vesicles which were prepared with different
      phospholipids and cholesterol of varying lipid compositions. They were compared
      on the potencies to modify membrane fluidity by measuring fluorescence
      polarization. Local anesthetics interacted with liposomal membranes to increase
      the fluidity. Increasing anionic phospholipids in membranes enhanced the membrane
      fluidizing effects of local anesthetics with the potency being
      cardiolipin>>phosphatidic acid>phosphatidylglycerol>phosphatidylserine.
      Cardiolipin was most effective on bupivacaine, followed by ropivacaine. Local
      anesthetics interacted differently with biomimetic membranes consisting of 10mol%
      cardiolipin, 50mol% other phospholipids and 40mol% cholesterol with the potency
      being bupivacaine>>ropivacaine>lidocaine>prilocaine, which agreed with the rank
      order of cardiotoxicity. Bupivacaine significantly fluidized 2.5-12.5mol%
      cardiolipin-containing membranes at cardiotoxicologically relevant
      concentrations. Bupivacaine is considered to affect lipid bilayers by interacting
      electrostatically with negatively charged cardiolipin head groups and
      hydrophobically with phospholipid acyl chains. The structure-dependent
      interaction with lipid membranes containing cardiolipin, which is preferentially
      localized in cardiomyocyte mitochondrial membranes, may be a mechanistic clue to
      explain the structure-selective cardiotoxicity of local anesthetics.

PMID- 19853593
TI  - Protective effect of anacardic acids from cashew (Anacardium occidentale) on
      ethanol-induced gastric damage in mice.
AB  - Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown
      to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and
      antitumor properties. Despite these known effects, hitherto there were no
      published reports on their likely gastroprotective effects. The present study was
      designed to verify whether AAs afford gastroprotection against the ethanol
      induced gastric damage and to examine the underlying mechanism(s). Gastric damage
      was induced by intragastric administration of 0.2mL of ethanol (96%). Mice in
      groups were pretreated orally with AAs (10, 30 and 100mg/kg), misoprostol (50
      microg/kg), or vehicle (2% Tween 80 in saline, 10mL/kg), 45min before ethanol
      administration. They were sacrificed 30min later, the stomachs excised, and the
      mucosal lesion area (mm(2)) measured by planimetry. Gastroprotection was assessed
      in relation to inhibition of gastric lesion area. To study the gastroprotective
      mechanism(s), its relations to capsaicin-sensitive fibers, endogenous
      prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed.
      Treatments effects on ethanol-associated oxidative stress markers GSH, MDA,
      catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured
      in gastric tissue. Besides, the effects of AAs on gastric secretory volume and
      total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose
      related gastroprotection against the ethanol damage and further prevented the
      ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and
      nitrate/nitrite. However, they failed to modify the gastric secretion or the
      total acidity. It was observed that the gastroprotection by AAs was greatly
      reduced in animals pretreated with capsazepine, indomethacin, l-NAME or
      glibenclamide. These results suggest that AAs afford gastroprotection principally
      through an antioxidant mechanism. Other complementary mechanisms include the
      activation of capsaicin-sensitive gastric afferents, stimulation of endogenous
      prostaglandins and nitric oxide, and opening of K(+)(ATP) channels. These
      combined effects are likely to be accompanied by an increase in gastric
      microcirculation.

PMID- 19853594
TI  - Imatinib assay by HPLC with photodiode-array UV detection in plasma from patients
      with chronic myeloid leukemia: Comparison with LC-MS/MS.
AB  - BACKGROUND: Imatinib, a competitive inhibitor of BCR-ABL tyrosine kinase, is now
      the first-line treatment for chronic myelogenous leukemia (CML). Therapeutic drug
      monitoring targeting trough plasma levels of about 1000ng/mL may help to optimize
      the therapeutic effect. METHODS: We developed a high-performance liquid
      chromatography (HPLC) method with UV/Diode Array Detection (DAD) for trough
      imatinib concentration determination in human plasma. Imatinib trough levels were
      measured in plasma from 65 CML patients using our method and LC-MS/MS as the
      reference method. Results with these two methods were compared using Deming
      regression, chi-square test, and sign test. RESULTS: The calibration curve was
      prepared in blank human plasma. HPLC-UV/DAD calibration curves were linear from
      80 to 4000ng/mL, and the limit of quantification was set at 80ng/mL. The between
      day variation was 6.1% with greater than 96% recovery after direct plasma
      deproteinization and greater than 98% recovery from the column. No significant
      differences in imatinib plasma levels were found between HPLC-UV/DAD and LC
      MS/MS. CONCLUSIONS: This HPLC-UV/DAD method was sufficiently specific and
      sensitive for imatinib TDM, with no evidence of interference. Our rapid
      inexpensive HPLC-UV/DAD method that requires only widely available equipment
      performs well for plasma imatinib assays.

PMID- 19853595
TI  - Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae
      exposed to ibogaine is adaptation to acute decrease in ATP energy pool.
AB  - Ibogaine has been extensively studied in the last decades in relation to its anti
      addictive properties that have been repeatedly reported as being addiction
      interruptive and craving eliminative. In our previous study we have already
      demonstrated induction of energy related enzymes in rat brains treated with
      ibogaine at a dose of 20mg/kg i.p. 24 and 72 h prior to proteomic analysis. In
      this study a model organism yeast Saccharomyces cerevisiae was cultivated with
      ibogaine in a concentration of 1mg/l. Energy metabolism cluster enzymes
      glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, enolase and
      alcohol dehydrogenase were induced after 5h of exposure. This is a compensation
      of demonstrated ATP pool decrease after ibogaine. Yeast in a stationary growth
      phase is an accepted model for studies of housekeeping metabolism of eukaryotes,
      including humans. Study showed that ibogaine's influence on metabolism is neither
      species nor tissue specific. Effect is not mediated by binding of ibogaine to
      receptors, as previously described in literature since they are lacking in this
      model.

PMID- 19853596
TI  - Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5,
      displaced [3H]-rolipram from high-affinity rolipram binding sites and reversed
      xylazine/ketamine-induced anesthesia.
AB  - The aim of the present study was to investigate the mode of action of luteolin on
      phisphodiesterase (PDE) 1-5, and the possible adverse effects, such as nausea,
      vomiting, and gastric hypersecretion, determined by replacing [(3)H]-rolipram
      binding and reversing xylazine/ketamine-induced anesthesia. The reversing effect
      was reported to occur through a presynaptic alpha(2)-adrenoceptor inhibition and
      trigger vomiting in ferrets. In contrast, clonidine, an alpha(2)-adrenoceptor
      agonist, prevented emesis induced by PDE4 inhibitors in ferrets. According to the
      Lineweaver-Burk analysis, luteolin (3-30 microM) competitively inhibited PDE1-5
      activities, with K(i) values of 15.0, 6.4, 13.9, 11.1, and 9.5 microM,
      respectively, which did not significantly differ from each other. The equilibrium
      dissociation constant (K(d)) and maximal density (B(max)) for [(3)H]-rolipram
      binding at high-affinity rolipram binding sites of guinea pig brain cell
      membranes were 10.1 nM and 3.7 p mol/g of tissue, respectively. The EC(50)
      (PDE4(H)) values of luteolin and Ro 20-1724, a selective PDE4 inhibitor, for
      displacing 2 nM [(3)H]-rolipram binding were 11.2 microM and 45.6 nM,
      respectively. The therapeutic (PDE4(H)/PDE4(L)) ratios of luteolin and Ro 20-1724
      were calculated to be 0.6, and 0.004, respectively. Both luteolin (10-30
      micromol/kg, s.c.) and Ro 20-1724 (0.1-1 micromol/kg, s.c.) significantly
      reversed the xylazine/ketamine-induced anesthesia in mice. Although luteolin non
      selectively and competitively inhibited PDE1-5, only PDE4 inhibition contributed
      to a reversing effect. In conclusion, because of the low therapeutic
      (PDE4(H)/PDE4(L)) ratio of luteolin, the gastrointestinal adverse effects such as
      nausea, vomiting and gastric hypersecretion should be carefully monitored,
      whenever luteolin is used for treating allergies, asthma or chronic obstructive
      pulmonary disease.

PMID- 19853597
TI  - MS275 enhances cytotoxicity induced by 5-fluorouracil in the colorectal cancer
      cells.
AB  - Histone deacetylases (HDACs) activity determines the acetylation status of
      histons, and has the ability to regulate gene expression through chromatin
      remodelling. HDACs are a promising target for pharmacological inhibition, since
      it has been discovered that some genes are repressed by their inappropriate
      recruitment. To test this we have addressed the hypothesis that histone
      deacetylase inhibitors SBHA and MS275 potentiate inhibitory effects of classical
      anti-colorectal cancer cytostatic, 5-fluorouracil (5-FU), on survival of
      colorectal cancer (CRC) cells in vitro. We are reporting here that HDAC
      inhibitors show potent synergistic interaction with 5-FU. The observed synergism
      between HDAC inhibitors and 5-FU is most probably related to the augmented
      apoptotic signal allowed for significant (both biological and statistical)
      reduction of the cytotoxic doses.

PMID- 19853598
TI  - Extracellular matrix components direct porcine muscle stem cell behavior.
AB  - In muscle tissue, extracellular matrix proteins, together with the vasculature
      system, muscle-residence cells and muscle fibers, create the niche for muscle
      stem cells. The niche is important in controlling proliferation and directing
      differentiation of muscle stem cells to sustain muscle tissue. Mimicking the
      extracellular muscle environment improves tools exploring the behavior of primary
      muscle cells. Optimizing cell culture conditions to maintain muscle commitment is
      important in stem cell-based studies concerning toxicology screening, ex vivo
      skeletal muscle tissue engineering and in the enhancement of clinical efficiency.
      We used the muscle extracellular matrix proteins collagen type I, fibronectin,
      laminin, and also gelatin and Matrigel as surface coatings of tissue culture
      plastic to resemble the muscle extracellular matrix. Several important factors
      that determine myogenic commitment of the primary muscle cells were characterized
      by quantitative real-time RT-PCR and immunofluorescence. Adhesion of high PAX7
      expressing satellite cells was improved if the cells were cultured on fibronectin
      or laminin coatings. Cells cultured on Matrigel and laminin coatings showed
      dominant integrin expression levels and exhibited an activated Wnt pathway. Under
      these conditions both stem cell proliferation and myogenic differentiation
      capacity were superior if compared to cells cultured on collagen type I,
      fibronectin and gelatin. In conclusion, Matrigel and laminin are the preferred
      coatings to sustain the proliferation and myogenic differentiation capacity of
      the primary porcine muscle stem cells, when cells are removed from their natural
      environment for in vitro culture.

PMID- 19853599
TI  - Exclusion of mRNPs and ribosomal particles from a thin zone beneath the nuclear
      envelope revealed upon inhibition of transport.
AB  - We have studied the nucleocytoplasmic transport of a specific messenger RNP
      (mRNP) particle, named Balbiani ring (BR) granule, and ribosomal RNP (rRNP)
      particles in the salivary glands of the dipteran Chironomus tentans. The passage
      of the RNPs through the nuclear pore complex (NPC) was inhibited with the
      nucleoporin-binding wheat germ agglutinin, and the effects were examined by
      electron microscopy. BR mRNPs bound to the nuclear basket increased in number,
      while BR mRNPs translocating through the central channel decreased, suggesting
      that the initiation of translocation proper had been inhibited. The rRNPs
      accumulated heavily in nucleoplasm, while no or very few rRNPs were recorded
      within nuclear baskets. Thus, the transport of rRNPs had been blocked prior to
      the entry into the baskets. Remarkably, the rRNPs had been excluded both from
      baskets and the space in between the baskets. We propose that normally basket
      fibrils move freely and repel RNPs from the exclusion zone unless the particles
      have affinity for and bind to nucleoporins within the baskets.

PMID- 19853600
TI  - Tumor endothelial marker 5 expression in endothelial cells during capillary
      morphogenesis is induced by the small GTPase Rac and mediates contact inhibition
      of cell proliferation.
AB  - Tumor endothelial marker (TEM) 5 is an adhesion G-protein-coupled receptor
      upregulated in endothelial cells during tumor and physiologic angiogenesis. So
      far, the mechanisms leading to upregulation of TEM5 and its function during
      angiogenesis have not been identified. Here, we report that TEM5 expression in
      endothelial cells is induced during capillary-like network formation on Matrigel,
      during capillary morphogenesis in a three-dimensional collagen I matrix, and upon
      confluence on a two-dimensional matrix. TEM5 expression was not induced by a
      variety of soluble angiogenic factors, including VEGF and bFGF, in subconfluent
      endothelial cells. TEM5 upregulation was blocked by toxin B from Clostridium
      difficile, an inhibitor of the small GTPases Rho, Rac, and Cdc42. The Rho
      inhibitor C3 transferase from Clostridium botulinum did not affect TEM5
      expression, whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation. An
      excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5
      antibody blocked contact inhibition of endothelial cell proliferation resulting
      in multilayered islands within the endothelial monolayer and increased vessel
      density during capillary formation. Based on our results we conclude that TEM5
      expression during capillary morphogenesis is induced by the small GTPase Rac and
      mediates contact inhibition of proliferation in endothelial cells.

PMID- 19853601
TI  - Synemin interacts with the LIM domain protein zyxin and is essential for cell
      adhesion and migration.
AB  - Synemin is a unique cytoplasmic intermediate filament protein for which there is
      limited understanding of its exact cellular functions. The single human synemin
      gene encodes at least two splice variants named alpha-synemin and beta-synemin,
      with the larger alpha-synemin containing an additional 312 amino acid insert
      within the C-terminal tail domain. We report herein that, by using the entire
      tail domain of the smaller beta-synemin as the bait in a yeast two-hybrid screen
      of a human skeletal muscle cDNA library, the LIM domain protein zyxin was
      identified as an interaction partner for human synemin. The synemin binding site
      in human zyxin was subsequently mapped to the C-terminal three tandem LIM-domain
      repeats, whereas the binding site for zyxin within beta-synemin is within the C
      terminal 332 amino acid region (SNbetaTII) at the end of the long tail domain.
      Transient expression of SNbetaTII within mammalian cells markedly reduced zyxin
      protein level, blocked localization of zyxin at focal adhesion sites and resulted
      in decreased cell adhesion and increased motility. Knockdown of synemin
      expression with siRNAs within mammalian cells resulted in significantly
      compromised cell adhesion and cell motility. Our results suggest that synemin
      participates in focal adhesion dynamics and is essential for cell adhesion and
      migration.

PMID- 19853602
TI  - The presence and distribution of elastin in the posterior and retrobulbar regions
      of the mouse eye.
AB  - The Presence and distribution of elastin in the posterior and retrobulbar regions
      of the mouse eye was investigated. Mice of two strains (C57/BL6 and DBA/2J) were
      studied at 2 months and 8-12 months of age. Light, confocal, and transmission
      electron microscopy were used to identify elastin, using immunohistochemical
      techniques and ultrastructural evaluation. Elastin was found in the following
      ocular structures: conjunctiva, muscle tendons, sclera, choroid, and meninges.
      The elastin in the sclera was most dense in a ring surrounding the peripapillary
      optic nerve head, with its presence in the inner sclera declining with greater
      distance from the nerve head. Elastin fibers were oriented in the sclera along
      what would be expected to be the principal stress directions generated from the
      intraocular pressure, though actual biomechanical measurements have not yet been
      made in the mouse sclera. Elastin comprises a portion of the mouse sclera and its
      distribution in the peripapillary area is similar to that in human eyes.

PMID- 19853603
TI  - Quantification of dynamic blood flow autoregulation in optic nerve head of rhesus
      monkeys.
AB  - Autoregulation capacity has been classically assessed with a 'two-point'
      measurement or static autoregulation (sAR). In such an approach, stabilized
      hemodynamic parameters are determined before and after a perfusion pressure
      challenge. Analysis of dynamic autoregulation (dAR), an early phase of blood flow
      response to a sudden perfusion pressure change is emerging as a preferred
      approach to assess the capacity of autoregulation in many non-ocular tissues and
      has developed rapidly in the last decade. The purpose of this study was to
      develop a method to quantify dAR in the optic nerve head (ONH). In six
      pentobarbital (6-9 mg/kg/h, IV) anesthetized rhesus monkeys, dAR was elicited by
      increasing intraocular pressure (IOP) from 10 to 30 or 40 mmHg (IOP(10-30)/IOP(10
      40)) manometrically via switch between reservoirs connected to the anterior
      chamber. Relative blood flow changes during dAR in the ONH, estimated with a
      laser speckle flowgraph (LSFG), were continuously measured for 1 min. Time-domain
      parameters of dAR response, including: BF(Deltamax) (maximal blood flow decrease,
      %), K(r) (descending slope of blood flow from baseline to BF(Deltamax)) and T(r)
      (descending time of blood flow from baseline to BF(Deltamax)) were extracted and
      analyzed offline. For each monkey, same procedure was repeated three times during
      three different visits. The test-retest repeatability and inter-ocular difference
      of the parameters was statistically evaluated. During IOP(10-30) and IOP(10-40),
      the mean arterial BP was 89 +/- 7 and 85 +/- 6 mmHg, respectively. Immediately
      after the reservoir was switched, the blood flow started to decline and reached
      maximal in approximately 4 s. The blood flow then returned back toward baseline
      despite continuous IOP increase, which took 8-11 s to reach the level of the
      raised reservoir. The general pattern of blood flow responses was similar between
      IOP(10-30) and IOP(10-40) and there was no statistically significant difference
      for T(r) (P > 0.05). However, IOP(10-40) caused greater BF(Deltamax) and deeper
      K(r) than IOP(10-30) (P < 0.0001 and P < 0.05, respectively). The blood flow
      during steady state, 5 min after IOP elevation, showed no statistically
      significant difference from baseline (P > 0.05). All dAR parameters (T(r), K(r)
      and BF(Deltamax)) showed no significant difference across the 3 visits (Repeat
      measures ANOVA, P = 0.7, 0.2 and 0.2, respectively); the corresponding
      coefficients of variance were 24%, 43% and 34% during IOP(10-30) and 11.8%, 30.3%
      and 19.0% during IOP(10-40). The mean dAR parameters between the eyes showed no
      statistically differences (P = 0.6) during both IOP(10-30) and IOP(10-40). The
      current study showed that a rapid ocular perfusion pressure decrease induced by a
      sudden IOP step increase evoked a transient and reproducible dAR response in the
      ONH of non-human primates measured with LSFG. Quantitative analysis of dAR may
      provide a direct view of vasomotorial activity in the resistant vessels and thus
      a new approach to assess the autoregulatory capacity in the ONH.

PMID- 19853604
TI  - Focus on molecules: ELOVL4.

PMID- 19853605
TI  - Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke
      after intra-arterial injection.
AB  - Cell-based treatments have been considered a promising therapy for neurological
      diseases. However, currently there are no clinically available methods to monitor
      whether the transplanted cells reach and remain in the brain. In this study we
      investigated the feasibility of detecting the distribution and homing of
      autologous bone-marrow mononuclear cells (BMMCs) labeled with Technetium-99 m
      ((99m)Tc) in a cell-based therapy clinical study for chronic ischemic stroke. Six
      male patients (ages 24-65 years) with ischemic cerebral infarcts within the
      middle cerebral artery (MCA) between 59 and 82 days were included. Cell dose
      ranged from 1.25x10(8) to 5x10(8). Approximately 2x10(7) cells were labeled with
      (99m)Tc and intra-arterially delivered together with the unlabeled cells via a
      catheter navigated to the MCA. None of the patients showed any complications on
      the 120-day follow-up. Whole body scintigraphies indicated cell homing in the
      brain of all patients at 2 h, while the remaining uptake was mainly distributed
      to liver, lungs, spleen, kidneys and bladder. Moreover, quantification of uptake
      in Single-Photon Emission Computed Tomography (SPECT) at 2 h showed preferential
      accumulation of radioactivity in the hemisphere affected by the ischemic infarct
      in all patients. However, at 24 h homing could only distinguished in the brains
      of 2 patients, while in all patients uptake was still seen in the other organs.
      Taken together, these results indicate that labeling of BMMCs with (99m)Tc is a
      safe and feasible technique that allows monitoring the migration and engraftment
      of intra-arterially transplanted cells for at least 24 h.

PMID- 19853606
TI  - Hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure
      susceptibility.
AB  - Disrupted ontogeny of forebrain inhibitory interneurons leads to neurological
      disorders, including epilepsy. Adult mice lacking the urokinase plasminogen
      activator receptor (Plaur) have decreased numbers of neocortical GABAergic
      interneurons and spontaneous seizures, attributed to a reduction of hepatocyte
      growth factor/scatter factor (HGF/SF). We report that by increasing endogenous
      HGF/SF concentration in the postnatal Plaur null mouse brain maintains the
      interneuron populations in the adult, reverses the seizure behavior and
      stabilizes the spontaneous electroencephalogram activity. The perinatal
      intervention provides a pathway to reverse potential birth defects and ameliorate
      seizures in the adult.

PMID- 19853607
TI  - Exposed proteins of the Schistosoma japonicum tegument.
AB  - The ability of the mammalian blood fluke Schistosoma japonicum to survive in the
      inhospitable environment of the mammalian bloodstream can be attributed, at least
      in part, to its host-exposed outer surface, called the tegument. The tegument is
      a dynamic organ and is involved in nutrition, immune evasion and modulation,
      excretion, osmoregulation and signal transduction. Given its importance for
      parasite survival, proteins exposed to the host at the surface of the tegument
      are ideal targets for the development of vaccines and drugs. By biotinylating
      live adult worms and using a combination of OFFGEL electrophoresis and tandem
      mass spectrometry 54 proteins were identified as putatively host-exposed in S.
      japonicum. These included glucose transport proteins, an amino permease, a
      leucine aminopeptidase and a range of transporters, heat shock proteins and novel
      immune-active proteins. Members of the tetraspanin protein family and a homologue
      of Sm 29, a tegument membrane protein from Schistosoma mansoni, both effective
      vaccine antigens in S. mansoni, were also identified. The fate of labelled
      surface proteins was monitored over time using electron microscopy and revealed
      that biotinylated proteins were rapidly internalised from the surface of the
      tegument and trafficked into the cytoplasmic bridges that connect the distal
      cytoplasm of the tegument to the underlying cell bodies. The results reported
      herein dramatically increase the number of S. japonicum proteins known to be
      exposed to the host and, hence, those of interest as therapeutic targets. The
      ability of the parasite to rapidly internalise proteins at its surface has
      implications for the development of vaccines and may explain how these parasites
      are able to avoid the host immune system for long periods of time.

PMID- 19853608
TI  - Phylogenetic analysis of nuclear and mitochondrial DNA reveals a complex of
      cryptic species in Crassicutis cichlasomae (Digenea: Apocreadiidae), a parasite
      of Middle-American cichlids.
AB  - We obtained nuclear ITS-1 and mitochondrial cox1 sequences from 225 Crassicutis
      cichlasomae adults collected in 12 species of cichlids from 32 localities to
      prospect for the presence of cryptic species. This trematode is commonly found in
      species of cichlids over a wide geographic range in Middle-America. Population
      level phylogenetic analyses of ITS-1 and cox1, assessments of genetic and
      haplotype diversity, and morphological observations revealed that C. cichlasomae
      represents a complex of seven cryptic species for which no morphological
      diagnostic characters have been discovered thus far. Bayesian and Maximum
      Likelihood analyses of concatenated datasets (906 bp) recovered eight lineages of
      C. cichlasomae, all with high posterior probabilities and bootstrap branch
      support. Values of genetic divergence between clades ranged from 1.0% to 5.2% for
      ITS-1, and from 7.2% to 30.0% for cox1. Morphological study of more than 300
      individuals did not reveal structural diagnostic traits for the species defined
      using molecular evidence. These observations indicate that some traditional
      morphological characters (e.g., testes position) have substantial intra-specific
      variation, and should be used with caution when classifying C. cichlasomae and
      their sister taxa. Additionally, phylogenetic analyses did not reveal a strict
      correlation between these cryptic species and their host species or geographic
      distribution, however it appears that genetic distinctiveness of these cryptic
      species was influenced by the diversification and biogeographical history of
      Middle-American cichlids.

PMID- 19853609
TI  - Developmental inflexibility of larval tapeworms in response to resource
      variation.
AB  - The timing of habitat switching in organisms with complex life cycles is an
      important life history characteristic that is often influenced by the larval
      growth environment. Under starvation, longer developmental times are frequently
      observed, probably as a consequence of developmental thresholds, but prolonged
      ontogeny sometimes also occurs under good conditions, as organisms may take
      advantage of the large potential gains in body size. I investigated whether
      variation in growth conditions affects the larval development time of a complex
      life cycle tapeworm (Schistocephalus solidus) in its copepod first host.
      Moreover, I reviewed patterns of developmental plasticity in larval tapeworms to
      assess the generality of my findings. Copepod starvation weakly retarded parasite
      growth but did not affect development. Worms grew bigger in larger copepods, but
      they developed at a similar rate in large and small hosts. Thus, S. solidus does
      not delay ontogeny under good conditions nor does it fail to reach a
      developmental threshold under poor conditions. Although unusual in comparison to
      free-living organisms, such inflexibility is common in tapeworms. Plasticity,
      namely prolonged ontogeny, has been mainly observed at high infection
      intensities. For S. solidus, there were large cross-environment genetic
      correlations for development, suggesting there may be genetic constraints on the
      evolution of developmental plasticity.

PMID- 19853610
TI  - Neural cell adhesion molecule is a cardioprotective factor up-regulated by
      metabolic stress.
AB  - Screening for cell surface proteins up-regulated under stress conditions may lead
      to the identification of new therapeutic targets. To search for genes whose
      expression was enhanced by treatment with oligomycin, a mitochondrial-F(0)F(1)
      ATP synthase inhibitor, signal sequence trapping was performed in H9C2 rat
      cardiac myoblasts. One of the genes identified was that for neural cell adhesion
      molecule (NCAM, CD56), a major regulator of development, cell survival,
      migration, and neurite outgrowth in the nervous system. Immunohistochemical
      analyses in a mouse myocardial infarction model revealed that NCAM was strongly
      expressed in residual cardiac myocytes in the infarcted region. Increased
      expression of NCAM was also found during the remodeling period in a rat model of
      hypertension-induced heart failure. Lentivirus-mediated knockdown of NCAM
      decreased the cell growth and survival following oligomycin treatment in H9C2
      cells. In primary rat neonatal cardiac myocytes, NCAM was also found to be up
      regulated and played a protective role following oligomycin treatment. Analyses
      of downstream signaling revealed that knockdown of NCAM significantly decreased
      the basal AKT phosphorylation level. In contrast, NCAM mimetic peptide P2d
      activated AKT and significantly reduced oligomycin-induced cardiomyocyte death,
      which was abolished by treatment with the PI3K inhibitor LY-294002 as well as
      overexpression of the dominant-negative AKT mutant. These findings demonstrate
      that NCAM is a cardioprotective factor up-regulated under metabolic stress in
      cardiomyocytes and augmentation of this signal improved survival.

PMID- 19853611
TI  - The crystal structure of the hinge domain of the Escherichia coli structural
      maintenance of chromosomes protein MukB.
AB  - MukB, a divergent structural maintenance of chromosomes (SMC) protein, is
      important for chromosomal segregation and condensation in gamma-proteobacteria.
      MukB and canonical SMC proteins share a characteristic five-domain structure.
      Globular N- and C-terminal domains interact to form an ATP-binding cassette-like
      ATPase or "head" domain, which is connected to a smaller dimerization or "hinge"
      domain by a long, antiparallel coiled coil. In addition to mediating
      dimerization, this hinge region has been implicated in both conformational
      flexibility and dynamic protein-DNA interactions. We report here the first
      crystallographic model of the MukB hinge domain. This model also contains
      approximately 20% of the coiled-coil domain, including an unusual coiled-coil
      deviation. These results will facilitate studies to clarify the roles of both the
      hinge and the coiled-coil domains in MukB function.

PMID- 19853612
TI  - Exploring the linkage dependence of polyubiquitin conformations using molecular
      modeling.
AB  - Posttranslational modification of proteins by covalent attachment of a small
      protein ubiquitin (Ub) or a polymeric chain of Ub molecules (called
      polyubiquitin) is involved in controlling a vast variety of processes in
      eukaryotic cells. The question of how different polyubiquitin signals are
      recognized is central to understanding the specificity of various types of
      polyubiquitination. In polyubiquitin, monomers are linked to each other via an
      isopeptide bond between the C-terminal glycine of one Ub and a lysine of the
      other. The functional outcome of polyubiquitination depends on the particular
      lysine involved in chain formation and appears to rely on linkage-dependent
      conformation of polyubiquitin. Thus, K48-linked chains, a universal signal for
      proteasomal degradation, under physiological conditions adopt a closed
      conformation where functionally important residues L8, I44, and V70 are
      sequestered at the interface between two adjacent Ub monomers. By contrast, K63
      linked chains, which act as a nonproteolytic regulatory signal, adopt an extended
      conformation that lacks hydrophobic interubiquitin contact. Little is known about
      the functional roles of the so-called "noncanonical" chains (linked via K6, K11,
      K27, K29, or K33, or linked head-to-tail), and no structural information on these
      chains is available, except for information on the crystal structure of the head
      to-tail-linked diubiquitin (Ub(2)). In this study, we use molecular modeling to
      examine whether any of the noncanonical chains can adopt a closed conformation
      similar to that in K48-linked polyubiquitin. Our results show that the eight
      possible Ub(2) chains can be divided into two groups: chains linked via K6, K11,
      K27, or K48 are predicted to form a closed conformation, whereas chains linked
      via K29, K33, or K63, or linked head-to-tail are unable to form such a contact
      due to steric occlusion. These predictions are validated by the known structures
      of K48-, K63-, and head-to-tail-linked chains. Our study also predicts structural
      models for Ub(2) chains linked via K6, K11, or K27. The implications of these
      findings for linkage-selective recognition of noncanonical polyubiquitin signals
      by various receptors are discussed.

PMID- 19853613
TI  - Identification of a new region of SARS-CoV S protein critical for viral entry.
AB  - Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) is
      initiated by specific interactions between the SARS-CoV spike (S) protein and its
      receptor ACE2. In this report, we screened a peptide library representing the
      SARS-CoV S protein sequence using a human immunodeficiency virus-based
      pseudotyping system to identify specific regions that affect viral entry. One of
      the 169 peptides screened, peptide 9626 (S residues 217-234), inhibited SARS-CoV
      S-mediated entry of the pseudotyped virions in 293T cells expressing a functional
      SARS-CoV receptor (human angiotensin-converting enzyme 2) in a dose-dependent
      manner (IC(50) approximately 11 microM). Alanine scanning mutagenesis was
      performed to assess the roles of individual residues within this region of S,
      which was previously uncharacterized. The effects included significant reductions
      in expression (K223A), viral incorporation (L218A, I230A, and N232A), and reduced
      viral entry (L224A, L226A, I228A, T231A, and F233A). Taken together, these
      results reveal a new region of the S protein that is crucial for SARS-CoV entry.

PMID- 19853614
TI  - The 19S ATPase S6a (S6'/TBP1) regulates the transcription initiation of class II
      transactivator.
AB  - Class II transactivator (CIITA) is the master regulator of the major
      histocompatibility class II transcription complex (MHC-II) and is critical for
      initiation of adaptive immune responses. We have previously demonstrated that the
      19S proteasome ATPase Sug1 plays a significant role in regulating CIITA activity
      and MHC-II expression. We now show that an additional component of the 19S
      complex, the 19S ATPase S6a (S6'/Tat-binding protein 1), is crucial for
      regulating cytokine-inducible transcription of CIITA. Lack of S6a negatively
      impacts CIITA activity and CIITA expression. Decreased expression of S6a
      significantly diminishes the recruitment of transcription factors to the CIITA
      interferon-gamma-inducible promoter [CIITA promoter IV (pIV)] and significantly
      decreases CIITApIV histone H3 and histone H4 acetylation, with a preferential
      loss of acetylation at H3 lysine 18 and H4 lysine 8. In addition, we provide
      evidence for the involvement of the 19S AAA (ATPases associated with diverse
      cellular activity) ATPase hexamer as the 19S ATPase S6b binds CIITApIV in an S6a
      dependent fashion and has effects similar to S6a on CIITApIV histone acetylation.
      These analyses demonstrate the importance of 19S ATPases in the assembly of
      CIITApIV transcription machinery and provide additional insight into the
      regulatory mechanisms of the 19S proteasome in mammalian transcription.

PMID- 19853615
TI  - Mechanical coupling in myosin V: a simulation study.
AB  - Myosin motor function depends on the interaction between different domains that
      transmit information from one part of the molecule to another. The interdomain
      coupling in myosin V is studied with restrained targeted molecular dynamics using
      an all-atom representation in explicit solvent. To elucidate the origin of the
      conformational change due to the binding of ATP, targeting forces are applied to
      small sets of atoms (the forcing sets, FSs) in the direction of their
      displacement from the rigor conformation, which has a closed actin-binding cleft,
      to the post-rigor conformation, in which the cleft is open. The "minimal" FS that
      results in extensive structural changes in the overall myosin conformation is
      composed of ATP, switch 1, and the nearby HF, HG, and HH helices. Addition of
      switch 2 to the FS is required to achieve a complete opening of the actin-binding
      cleft. The restrained targeted molecular dynamics simulations reveal the
      mechanical coupling pathways between (i) the nucleotide-binding pocket (NBP) and
      the actin-binding cleft, (ii) the NBP and the converter, and (iii) the actin
      binding cleft and the converter. Closing of the NBP due to ATP binding is tightly
      coupled to the opening of the cleft and leads to the rupture of a key hydrogen
      bond (F441N/A684O) between switch 2 and the SH1 helix. The actin-binding cleft
      may mediate the rupture of this bond via a connection between the HW helix, the
      relay helix, and switch 2. The findings are consistent with experimental studies
      and a recent normal mode analysis. The present method is expected to be useful
      more generally in studies of interdomain coupling in proteins.

PMID- 19853616
TI  - In vitro dynamic visualization analysis of fluorescently labeled minor capsid
      protein IX and core protein V by simultaneous detection.
AB  - Oncolytic adenoviruses represent a promising therapeutic medicine for human
      cancer therapy, but successful translation into human clinical trials requires
      careful evaluation of their viral characteristics. While the function of
      adenovirus proteins has been analyzed in detail, the dynamics of adenovirus
      infection remain largely unknown due to technological constraints that prevent
      adequate tracking of adenovirus particles after infection. Fluorescence labeling
      of adenoviral particles is one new strategy designed to directly analyze the
      dynamic processes of viral infection in virus-host cell interactions. We
      hypothesized that the double labeling of an adenovirus with fluorescent proteins
      would allow us to properly analyze intracellular viruses and the fate of viral
      proteins in a live analysis of an adenovirus as compared to single labeling.
      Thus, we generated a fluorescently labeled adenovirus with both a red fluorescent
      minor capsid protein IX (pIX) [pIX monomeric red fluorescent protein 1 (mRFP1)]
      and a green fluorescent minor core protein V (pV) [pV enhanced green fluorescent
      protein (EGFP)], resulting in Ad5-IX-mRFP1-E3-V-EGFP. The fluorescent signals for
      pIX-mRFP1 and pV-EGFP were detected within 10 min in living cells. However, a
      growth curve analysis of Ad5-IX-mRFP1-E3-V-EGFP showed an approximately 150-fold
      reduced production of the viral progeny at 48 h postinfection as compared to
      adenovirus type 5. Interestingly, pIX-mRFP1 and pV-EGFP were initially localized
      in the cytoplasm and nucleolus, respectively, at 18 h postinfection. These
      proteins were observed in the nucleus during the late stage of infection, and
      relocalization of the proteins was observed in an adenoviral-replication
      dependent manner. These results indicate that simultaneous detection of
      adenoviruses using dual-fluorescent proteins is suitable for real-time analysis,
      including identification of infected cells and monitoring of viral spread, which
      will be required for a complete evaluation of oncolytic adenoviruses.

PMID- 19853617
TI  - Bicarbonate-mediated stimulation of RegA, the global virulence regulator from
      Citrobacter rodentium.
AB  - The global virulence regulatory protein RegA, an AraC-like regulator, controls
      the expression of more than 60 genes in the mouse enteric pathogen Citrobacter
      rodentium. In the presence of bicarbonate, RegA activates the transcription of a
      number of virulence determinants and inhibits the expression of a series of
      housekeeping genes. To elucidate the molecular mechanism by which bicarbonate
      stimulates RegA activity, we carried out biophysical and mutational analyses. Our
      data indicate that RegA exists as a dimer in solution regardless of bicarbonate
      concentration. A leucine zipper, located in the region downstream of the N
      terminal domain, is responsible for dimerisation. The N-terminal arm itself is
      involved in modulating the response to bicarbonate, which appears to bind to a
      region comprising a series of beta-sheets within the N-terminal domain. The
      presence of bicarbonate relieves the autoinhibition of RegA activity by its N
      terminal arm. RegA is the first example of a bacterial virulence regulator that
      utilises the light switch mechanism, previously described for the Escherichia
      coli AraC protein, to respond to a gut-associated effector that controls its
      activity.

PMID- 19853618
TI  - Factors that determine the efficiency of HIV-1 strand transfer initiated at a
      specific site.
AB  - Human immunodeficiency virus-1 employs strand transfer for recombination between
      two viral genomes. We have previously provided evidence that strand transfer
      proceeds by an invasion-mediated mechanism in which a DNA segment on the original
      RNA template is invaded by a second RNA template at a gap site. The initial RNA
      DNA hybrid then expands until the DNA is fully transferred. Ribonuclease H (RNase
      H) cleavages and nucleocapsid protein (NC) were required for long-distance
      propagation of the hybrid. Evaluation was performed on a unique substrate, with a
      short gap serving as a precreated invasion site. In our current work, this
      substrate provided an opportunity for us to test what factors influence a
      specific invasion site to support transfer, and to distinguish factors that
      influence invasion site creation from those that impact later steps. RNase H can
      act in a polymerization-dependent or polymerization-independent mode.
      Polymerization-dependent and polymerization-independent RNase H were found to be
      important in creating efficiently used invasion sites in the primer-donor
      complex, with or without NC. Propagation and terminus transfer steps, emanating
      from a precreated invasion site in the presence of NC, were stimulated by
      polymerization-dependent, but not polymerization-independent, RNase H. RNase H
      can carry out primary and secondary cleavages during synthesis. While both modes
      of cleavage promoted invasion, only primary cleavage promoted propagation in the
      presence of NC in our system. These observations suggest that once invasion is
      initiated at a short gap, it can propagate through an adjacent region interrupted
      only by nicks, with help by NC. We considered the possibility that propagation
      solely by strand exchange was a significant contributor to transfers. However, it
      did not promote transfer even if synthetic progress of reverse transcriptase was
      intentionally slowed, consistent with strand exchange by random walk in which
      rate declines precipitously with distance.

PMID- 19853620
TI  - A synergistic approach for neural repair: cell transplantation and induction of
      endogenous precursor cell activity.
AB  - Stem cell research offers enormous potential for treating many diseases of the
      nervous system. At present, therapeutic strategies in stem cell research
      segregate into two approaches: cell transplantation or endogenous cell
      stimulation. Realistically, future cell therapies will most likely involve a
      combination of these two approaches, a theme of our current research. Here, we
      propose that there exists a 'synergy' between exogenous (transplanted) and
      endogenous stem cell actions that can be utilized to achieve therapeutic ends.
      Elucidating mechanisms underlying this exogenous-endogenous stem cell synergism
      may lead to the development of optimal cell therapies for neural disorders.

PMID- 19853619
TI  - Discriminative stimulus effects of L-838,417 (7-tert-butyl-3-(2,5-difluoro
      phenyl)-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-[1,2,4]triazolo[4,3
      b]pyridazine): role of GABA(A) receptor subtypes.
AB  - Previous reports suggest that gamma-aminobutyric acid type A (GABA(A)) receptors
      containing alpha1 subunits may play a pivotal role in mediating the
      discriminative stimulus effects of benzodiazepines (BZs). L-838,417 (7-tert-Butyl
      3-(2,5-difluoro-phenyl)-6-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)
      [1,2,4]triazolo[4,3-b]pyridazine) is a GABA(A) receptor modulator with intrinsic
      efficacy in vitro at alpha2, alpha3, and alpha5 subunit-containing GABA(A)
      receptors, and little demonstrable intrinsic efficacy in vitro at alpha1 subunit
      containing GABA(A) receptors. The present study evaluated the discriminative
      stimulus effects of L-838,417 in order to determine the extent to which the
      alpha2, alpha3, and alpha5 subunit-containing GABA(A) receptors contribute to the
      interoceptive effects of BZ-type drugs. Squirrel monkeys (Saimiri sciureus) were
      trained to discriminate L-838,417 (0.3 mg/kg, i.v.) from vehicle under a 5
      response fixed-ratio schedule of food reinforcement. Under test conditions, L
      838,417 administration resulted in dose-dependent increases in drug-lever
      responding that were antagonized by the BZ-site antagonist, flumazenil.
      Administration of non-selective BZs, compounds with 10-fold greater affinity for
      alpha1 subunit-containing GABA(A) receptors compared to alpha2, alpha3, and
      alpha5 subunit-containing GABA(A) receptors, barbiturates and ethanol (which
      modulate the GABA(A) receptor via a non-BZ site), all resulted in a majority of
      responses on the L-838,417-paired lever (65-100% drug-lever responding). betaCCT,
      an antagonist that binds with 20-fold greater affinity for alpha1 subunit
      containing GABA(A) receptors relative to alpha2, alpha3, and alpha5-containing
      GABA(A) receptors, had no significant effect on the discriminative stimulus
      effects of L-838,417 or the L-838,417-like effects of diazepam or zolpidem. These
      data suggest that efficacy at alpha2, alpha3, and/or alpha5 subunit-containing
      GABA(A) receptors likely are sufficient for engendering BZ-like discriminative
      stimulus effects.

PMID- 19853621
TI  - Physical activity interventions and changes in perceived home and facility
      environments.
AB  - OBJECTIVE: To examine changes in environmental perceptions over time and
      associations between changes in perceptions and physical activity among
      participants in two physical activity interventions. METHODS: Two independent
      trials were examined. Project STRIDE (STRIDE) (N=239) was conducted from 2000 to
      2004 in Rhode Island. Step into Motion (SIM) (N=249) was conducted from 2003 to
      2006 in Rhode Island and Pennsylvania. Both trials tested various delivery
      channels for providing individually tailored motivational materials to increase
      physical activity among sedentary adults. Neither intervention aimed to change
      perceptions of the environment. At baseline, 6, and 12 months, surveys assessed
      physical activity and perceived facility and home equipment availability.
      RESULTS: In both trials, perceived facility availability increased from baseline
      to 6 months. Significant increases continued from 6 to 12 months in SIM only.
      Increases were not significantly different by treatment group. Perceived home
      equipment availability also increased from baseline to 6 months in both trials
      and from 6 to 12 months in SIM only. In STRIDE, greater increases were observed
      for intervention compared to control participants. Increased facility and home
      equipment availability were associated with increased minutes of physical
      activity in both trials. CONCLUSIONS: Perceived facility and home equipment
      availability improved during participation in two individual-level physical
      activity interventions.

PMID- 19853622
TI  - Altered adult locomotor activity in rats from phencyclidine treatment on
      postnatal days 7, 9 and 11, but not repeated ketamine treatment on postnatal day
      7.
AB  - Neonatal ketamine (KET) or phencyclidine (PCP) treatment can trigger apoptotic
      neurodegeneration in rodents. Previously, we described KET- and PCP-induced
      altered body weight and home cage, slant board and forelimb hang behaviors in
      preweaning rats (Boctor et al., 2008). In that study, L-carnitine (LC) attenuated
      the KET-induced behavioral alterations and body weight decrements. The four
      subcutaneous (sc) treatment groups were: (1) saline; (2) 10 mg/kg PCP on PNDs 7,
      9 and 11; (3) 20 mg/kg KET (6 injections; one every 2h on PND 7); or (4) a
      regimen of KET and 250 mg/kg LC (KLC) both administered on PND 7, with additional
      250 mg/kg doses of LC on PNDs 8-11. A portion of each treatment group was
      evaluated for postweaning behaviors which included grip strength and motor
      coordination (postnatal days (PNDs) 22 or 71), locomotor sensitization (PND 42),
      spatial alternation (PNDs 22-70) and residential running wheel activity (PNDs 72
      77). On PND 42 or 78, whole and regional brain weights were measured. Grip
      strength and motor coordination were unaffected at either age by neonatal
      treatment. On PND 42, neonatally treated KET- or KLC-treated rats responded to a
      challenge of 5mg/kg KET with activity similar to controls that received the same
      challenge. Neonatal PCP treatment, however, induced significant sensitization to
      a challenge of 3mg/kg PCP on PND 42 relative to controls that received the same
      challenge, causing increased activity which was especially profound in females.
      Performance on a continuous spatial alternation task requiring a "win-shift, lose
      stay" strategy appeared unaffected by neonatal KET or KLC treatment. PCP
      treatment, however, caused significantly increased random responding and shorter
      choice latencies. In addition, neonatal PCP treatment elevated light and dark
      period running wheel activity and reduced PND 42 and 78 body and whole brain
      weights. These findings provide further evidence that PCP treatment on PNDs 7, 9,
      and 11 causes subtle cognitive deficits and long-term alterations in activity
      that are unrelated to deficits in grip strength or motor coordination. Further,
      repeated KET treatment on PND 7 does not appear to result in severe behavioral
      modifications.

PMID- 19853623
TI  - Assessing the effects of the neonicotinoid insecticide imidacloprid in the
      cholinergic synapses of the stellate cells of the mouse cochlear nucleus using
      whole-cell patch-clamp recording.
AB  - Imidacloprid (IMI) is widely used systemic insecticide that acts as an agonist on
      nicotinic acetylcholine receptors (nAChRs). IMI has been reported to be more
      active against insect nAChRs (EC(50) 0.86-1 microM) than it is against mammalian
      nAChRs (EC(50) 70 microM). The objective of this study was to determine to what
      extent IMI affects the nAChRs of the stellate cells of mouse cochlear nucleus
      (CN), using whole-cell patch-clamp recording. Puff application of 1 microM IMI
      had no significant effect on the membrane properties of the neurons tested, while
      a concentration of 10 microM caused a significant depolarizing shift in the
      membrane potential and resulted in increases in the fluctuation of the membrane
      potential and in the frequency of miniature postsynaptic potentials (mpps) within
      less than a minute of exposure. IMI at concentrations >or=50 microM caused a
      significant depolarizing shift in the membrane potential, accompanied by a marked
      increase in the frequency of action potential. IMI decreased the membrane input
      resistance and the membrane time constants. Bath application of 50 microM d
      tubocurarine (d-TC) reversibly blocked the depolarizing shift of the resting
      membrane potential and the spontaneous firing induced by IMI application in
      current clamp and blocked the inward currents through nicotinic receptors induced
      by IMI application in voltage clamp. Similarly, 100 nM alpha-bungarotoxin (alpha
      BgTx) blocked the spontaneous firing induced by IMI (n=3). The amplitude of the
      100 microM IMI-induced inward current at -60 mV holding potential was 115.0+/
      16.2 pA (n=7). IMI at a concentration of 10 microM produced 11.3+/-3.4 pA inward
      current (n=4). We conclude that exposure to IMI at concentrations >or=10 microM
      for <1 min can change the membrane properties of neurons that have nAChRs and, as
      a consequence, their function.

PMID- 19853624
TI  - AICAR (5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside) increases the
      production of toxic molecules and affects the profile of cytokines release in LPS
      stimulated rat primary microglial cultures.
AB  - AICAR (5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside, Acadesine, AICA
      riboside) is an activator of AMP-activated protein kinase (AMPK). The results of
      recent studies suggest that AICAR, in addition to its application for treating
      metabolic disorders, may also have therapeutic potential for treating
      neuroinflammatory diseases where reactive microglia play an etiological role.
      However, the molecular mechanisms of action by which AICAR exerts its anti
      inflammatory effects still remain unclear or controversial. In this paper we
      attempt to evaluate the effects of AICAR on non-stimulated and LPS-activated rat
      primary microglial cell cultures. The presented evidence supports the conclusion
      that AMPK activated by AICAR is involved in regulation of ROS and cytokine
      production (IL-1 beta, TNF-alpha (6h), IL-10 and TGF-beta) as well as arginase I
      and PGC-1alpha expression. Furthermore, we found that the effects of AICAR on IL
      6 and TNF-alpha (12, 24h) release and on the expression of iNOS and NF-kappaB p65
      are not AMPK-dependent because the pre-treatment of LPS-activated microglia with
      compound C (a pharmacological inhibitor of AMPK) did not reverse the effect of
      AICAR. The results of the presented study provide additional data about AMPK
      dependent and -independent mechanisms whereby AICAR may modulate inflammatory
      response of microglia.

PMID- 19853625
TI  - Associations between immunologic, inflammatory, and oxidative stress markers with
      severity of depressive symptoms: an analysis of the 2005-2006 National Health and
      Nutrition Examination Survey.
AB  - Previous studies have demonstrated increased levels of serum markers of systemic
      inflammation and immune system function among individuals with depressive
      symptoms. Despite these observations, the biological mechanisms behind this
      association remain elusive. The objective of the present analysis was to examine
      the individual and joint associations of white blood cell counts, platelet
      counts, and C-reactive protein with depression severity and to determine whether
      oxidative stress might mediate these associations. We conducted an analysis of
      3867 subjects from the 2005-2006 National Health and Nutritional Examination
      Survey. Ordinal logistic regression was used to assess associations between three
      levels of depression symptom severity (as measured by the nine-item Patient
      Health Questionnaire) and serum C-reactive protein, white blood cell counts,
      platelet counts, and four surrogate markers of oxidative stress. Covariates
      included sex, age, smoking status, physical activity, education, poverty to
      income ratio, as well as medication use and medical conditions influencing
      inflammation levels. In separate models, the risk of moderate to severe
      depression was significantly greater in the highest quartiles of CRP (OR=1.84. 95
      percent confidence interval (CI)=1.35-2.52), WBC (OR=1.70, CI=1.31-2.19), and
      platelet counts (OR=1.41, CI=1.13-1.76) after adjusting for basic
      sociodemographic and behavioral factors. After additional adjustment for
      medication use and oxidative stress surrogate measures, the highest quartile of
      WBC counts remained associated with depression (OR=1.60, CI=1.23-2.09).
      Adjustment for oxidative stress measures did not substantially affect estimated
      associations of inflammation/immunologic markers. In summary, we observed
      significantly elevated white blood cell counts among subjects with moderate and
      severe depression, and oxidative stress and a medical history of inflammatory
      diseases do not appear to mediate this association. Although limited through its
      use of cross-sectional data, this is the first analysis to simultaneously
      consider immunologic and oxidative stress markers. Further research is needed to
      identify the biological basis for this persistent association.

PMID- 19853626
TI  - A review on the inferior temporal cortex of the macaque.
AB  - In our review, we summarize recent advances in the research of the inferior
      temporal cortex (ITC) of the macaque monkey. This area of the cortex is known to
      have a crucial role in visual shape recognition and is regarded as being at the
      end stage of the so-called ventral visual pathway. In the last decade, several
      new findings appeared in the field without being integrated in a coherent view
      about the function, position, and operating principles of the area. During this
      decade, experimental techniques developed a great deal, and the way we look at
      the brain and brain function changed too. In this review, we try to integrate
      knowledge about the ITC to the changing view about the brain while outlining the
      work that has been done in the last decade.

PMID- 19853627
TI  - Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance.
AB  - HIV protease plays a crucial role in the viral life cycle and is essential for
      the generation of mature infectious virus particles. Detailed knowledge of the
      structure of HIV protease and its substrate has led to the design of specific HIV
      protease inhibitors. Unfortunately, resistance to all protease inhibitors (PIs)
      has been observed and the genetic basis of resistance has been well documented
      over the past 15 years. The arrival of the early PIs was a pivotal moment in the
      development of antiretroviral therapy. They made possible the dual class triple
      combination therapy that became known as HAART. However, the clinical utility of
      the first generation of PIs was limited by low bioavailability and high pill
      burdens, which ultimately reduced adherence and limited long-term viral
      inhibition. When therapy failure occurred multiple protease resistance mutations
      were observed, often resulting in broad class resistance. To combat PI-resistance
      development, second-generation approaches have been developed. The first advance
      was to increase the level of existing PIs in the plasma by boosting with
      ritonavir. The second was to develop novel PIs with high potency against the
      known PI-resistant HIV protease variants. Both approaches increased the number of
      protease mutations required for clinical resistance, thereby raising the genetic
      barrier. This review provides an overview of the history of protease inhibitor
      therapy, its current status and future perspectives. It forms part of a special
      issue of Antiviral Research marking the 25th anniversary of antiretroviral drug
      discovery and development, vol. 85, issue 1, 2010.

PMID- 19853628
TI  - A new tool linking human cytomegalovirus drug resistance mutations to resistance
      phenotypes.
AB  - Drug resistant strains of human cytomegalovirus (HCMV) in patients at risk may
      increasingly develop into a problem in the clinical setting. Genotypic resistance
      testing is becoming the method of choice, but requires previous phenotypic
      characterisation of each newly found mutation. In order to facilitate the
      interpretation of the patient's CMV sequence data, a web-based search tool was
      generated that links the sequence to a database containing all published UL97
      (protein kinase) and UL54 (DNA polymerase) mutations and corresponding antiviral
      drug susceptibility phenotypes. It is reasonable to assume that HCMV drug
      resistance testing will provide relevant data for an adjustment of therapy and on
      prognosis of clinical outcome. HCMV drug susceptibility testing will become even
      more important once new drugs will be available for therapy allowing a wider
      choice of antiviral agents to treat HCMV disease. These topics will also play a
      pivotal role for optimising antiviral therapy of HCMV- and other viral diseases.

PMID- 19853629
TI  - Dopamine D4 receptor (D4R) deletion in mice does not affect operant responding
      for food or cocaine.
AB  - In this study we examined the genetic contribution of the D4R in food and cocaine
      self-administration using D4R mice. Mice were examined for operant responding to
      food pellets or intravenous cocaine. Compared to wild-type mice (D4R(+/+)), both
      heterozygous (D4R(+/-)) and knockout (D4R(-/-)) mice showed no difference in
      responding for food or cocaine. Our findings suggest that the D4R is not directly
      involved in mediating operant response behaviors for food or cocaine.

PMID- 19853630
TI  - My thoughts through a robot's eyes: an augmented reality-brain-machine interface.
AB  - A brain-machine interface (BMI) uses neurophysiological signals from the brain to
      control external devices, such as robot arms or computer cursors. Combining
      augmented reality with a BMI, we show that the user's brain signals successfully
      controlled an agent robot and operated devices in the robot's environment. The
      user's thoughts became reality through the robot's eyes, enabling the
      augmentation of real environments outside the anatomy of the human body.

PMID- 19853631
TI  - Transcription factor AP1 modulates the internal promoter activity of bovine foamy
      virus.
AB  - Foamy virus contains two promoters, which are the canonical long terminal repeat
      (LTR) promoter and the internal promoter (IP). FV gene expression was considered
      to initiate at the internal promoter. However, little was known about how basal
      transcription of IP was triggered by the host cellular factors. Previous studies
      found some cellular proteins could affect HFV viral replication, but it was no
      known whether the AP1 signal pathway was involved in the activation of viral
      replication or not. In this study, we reported that treatment with TPA or AP1
      increased basal transcription of IP and did not affect basal transcription of the
      promoter in the LTR. In addition, the c-Jun mutant blocked the IP activity
      stimulated by TPA. Two AP1 binding sites located in BFV-IP promoter were found by
      bioinformatics and mutants of two AP1 binding sites decreased luciferase reporter
      activity of IP activated by AP1. EMSA assay showed that two AP1 binding sites
      could bind to c-Jun/c-Fos heterodimeric. We also found TPA and AP1 enhanced
      BFV3026 replication. Taken together, these data suggested that AP1 was a positive
      regulator of BFV internal promoter.

PMID- 19853632
TI  - Serotonin transporter gene promoter polymorphism affects the severity of binge
      eating in general population.
AB  - OBJECTIVE: The s-allele of the 5-HTTLPR has been suggested to lead to the
      development of less efficient and less flexible 5-HT system and has been
      associated to different forms of psychopathology. It has also been shown that
      alterations in serotonergic activity contribute to the pathophysiology of binge
      eating but it is not clear which changes in 5-HT function observed in eating
      disorder patients represent trait vs state effect. We investigated the
      association between the 5-HTTLPR and binge eating in a population-representative
      sample of women, and tested whether the 5-HTTLPR genotype influences the severity
      of binge eating. METHODS: The sample was based on women participating in the
      third wave of the Estonian Children Personality, Behaviour and Health Study. EDI
      2 subscales - drive for thinness and bulimia - were used to assess eating
      behaviour and attitudes. Barratt Impulsiveness Scale (BIS-11) and State and Trait
      Anxiety Inventory (STAI) were used to measure impulsivity and anxiety.
      Participants were genotyped for the 5-HTTLPR. RESULTS: There was no 5-HTTLPR
      genotype effect on binge eating even after the covarying effect of impulsivity
      and anxiety was controlled for. However, women prone to binge eating and carrying
      the s-allele showed significantly higher levels of bulimia scores, and among
      them, women with s/s genotype had also higher levels of state anxiety and
      tendency for higher impulsivity. CONCLUSIONS: While the 5-HTTLPR genotype does
      not predict symptoms of eating disorder in general population, the s-allele, and
      especially the s/s genotype increases the risk for affective instability and
      symptom severity.

PMID- 19853633
TI  - Risk assessment of pesticides and heavy metals contaminants in vegetables: a
      novel bioassay method using Daphnia magna Straus.
AB  - Cucumber and potato samples of known levels of pesticides and heavy metal
      residues, as respectively measured by gas chromatography and atomic absorption,
      were subjected to a bioassay method using Daphnia magna in order to assess the
      potential of the toxic hazard of their contaminants. Based on the estimated
      lethal time for 50% mortality (LT50) in daphnids, we suggested a classification
      to categorize toxic hazards in six definite ratings. Either samples of cucumbers
      (from conventional, greenhouse and organic farming) or potatoes (from
      conventional and organic farming) were evaluated for toxic hazard of the mixtures
      of pesticide residues and heavy metals, as well as mixtures of both. Accordingly,
      a 53.7% of cucumber samples were ranked as "Highly Toxic: HT"; a 18.5%
      "Moderately Toxic: MT); a 9.3% "Slightly Toxic: ST"; and a 18.5% "Practically Non
      Toxic: NT". For potato samples, the ranking pattern to different classes was:
      Extremely Toxic: ET (LT50=<1h) for 11.1%; Very Toxic: VT (LT50=1-<3h) for 50.0%;
      HT (LT50=3-<12h) for 13.9%; MT (LT50=12-<24h) for 11.1%; ST (LT50=24-48 h) for
      0.0%; and NT (LT50= >48 h) for 13.9% of the samples bioassayed.

PMID- 19853634
TI  - A subchronic oral toxicity study of almond skins in rats.
AB  - Almond skins have been suggested to have some potential benefits. To investigate
      the subchronic toxicity of almond skins, a 90-feeding study was conducted in
      rats. Sprague-Dawley rats were randomly divided into four groups (20
      rats/sex/group) and received a diet containing 0%, 2.5%, 5.0% and 10% (w/w)
      almond skins for 90 days. Daily clinical observations and weekly measurement of
      body weights and food consumption were conducted. Ophthalmic examinations were
      performed at pre-test and termination. Blood samples were obtained on day 46 and
      day 91 for the measurement of hematology, coagulation and clinical chemistry
      parameters. Urine samples were collected on day 91 for urinalysis. Animals were
      euthanized for necropsy. Selected organs were weighted and recorded. Histological
      examination was performed on all tissues from animals in the control and high
      dose groups. No mortality, body weight, ophthalmic abnormalities or treatment
      related findings in clinical observations, hematology, coagulation, urinalysis
      parameters, macroscopic or microscopic examinations were observed. Differences
      between treated and control groups in weight gain, food consumption, clinical
      chemistry, and organ weight were not considered treatment-related. The no
      observed-adverse-effect-level (NOAEL) for almond skins was considered to be 10%
      (w/w) for both genders (females, 9.7 g/kg body weight/day; males, 8.2g/kg body
      weight/day).

PMID- 19853635
TI  - Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague
      Dawley rats.
AB  - Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax
      (LMPW) and low viscosity white oils can cause inflammatory changes in the liver
      and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast,
      only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes
      in the liver. In this study, the response of female F-344 and S-D rats was
      compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the
      F-344 rats were significantly greater than in the S-D rats: increased liver and
      splenic weights and inflammatory changes (hepatic microgranulomas) in these
      tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were
      observed in both strains but the effects were substantially greater in the F-344
      rats. Cellular markers of inflammation were examined in a subset of rats from
      each group using immunohistochemical staining. An increase in staining for CD3 (T
      cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated
      with an increase in lymphoid cells in the livers of treated F-344 rats. The
      majority of macrophages in the hepatic microgranulomas of treated F-344 rats were
      negative for the ED2 marker, indicating a likely origin from non-resident
      macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia
      in treated F-344 rats. However, lysozyme staining (indicating activation of
      epithelioid macrophages) decreased with increasing granuloma size. Non-ED2
      expressing cells may have been recruited but not sufficiently activated to be
      lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in
      previous studies of LMPW were also seen in the F-344 rats in this study but not
      in the S-D rats. Chemical analysis showed that MHC accumulated in livers from
      treated F-344 but not S-D rats and the concentration was more than 2-fold greater
      in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more
      immunologically sensitive to a number of agents than other rat strains and the
      results of this study suggest that this may contribute, along with
      pharmacokinetic differences, to the inflammatory response of F-344 rats to
      dietary MHCs.

PMID- 19853636
TI  - Comparative study of quality characteristics of meju, a Korean soybean
      fermentation starter, made by soybeans germinated under dark and light
      conditions.
AB  - This study was conducted to evaluate the effect of dark and light conditions on
      the quality characteristics of whole soybean meju, a Koran soybean fermentation
      starter, made by germinated soybeans. The sprouting rates of soybeans under dark
      and light conditions after 24h were 25.6+/-1.2% and 20.5+/-1.5%, respectively and
      reaching to a level of 99.4+/-0.4% and 98.9+/-0.5%, respectively at 60h. The pH,
      moisture contents and amino-type nitrogen contents had no significant differences
      under dark and light conditions, however, the contents were significantly
      different as compared to control. Also there was a significant difference in the
      color change values of whole soybean meju under dark and light conditions. The
      compositions of total organic acids in MNG, MGD and MGL were noted to be 942.2+/
      111.0, 1075+/-120.2 and 1019+/-108.1mg%, respectively. However, no significant
      differences were observed in free amino acid contents of MNG, MGD and MGL. It was
      observed that isoflavone contents were significantly differed in MGD and MGL as
      compared to MNG.

PMID- 19853637
TI  - Anomalous genotoxic responses induced in mouse lymphoma L5178Y cells by potassium
      bromate.
AB  - Potassium bromate (KBrO3) is a well-established rodent kidney carcinogen and its
      oxidising activity is considered to be a significant factor in its mechanism of
      action. Although it has also been shown to be clearly genotoxic in a range of in
      vivo and in vitro test systems, surprisingly, it is not readily detected in
      several cell lines using the standard alkaline Comet assay. However, previous
      results from this laboratory demonstrated huge increases in tail intensity by
      modifying the method to include incubation with either human 8-oxodeoxyguanosine
      DNA glycosylase-1 (hOGG1) or bacterial formamidopyrimidine DNA glycosylase (FPG)
      indicating that, as expected, significant amounts of 8-oxodeoxyguanosine (8-OHdG)
      were induced. The purpose of this work, therefore, was to investigate why KBrO3,
      in contrast to other oxidising agents, gives a relatively poor response in the
      standard Comet assay. Results confirmed that it is a potent genotoxin in mouse
      lymphoma L5178Y cells inducing micronuclei and mutation at the tk and hprt loci
      at relatively non-cytotoxic concentrations. Subsequent time-course studies
      demonstrated that substantial amounts of 8-OHdG appear to remain in cells 24h
      after treatment with KBrO3 but result in no increase in frank stand breaks (FSB)
      even though phosphorylated histone H2AX (gamma-H2AX) antibody labelling confirmed
      the presence of double-strand breaks. Using bromodeoxyuracil (BrdU) incorporation
      together with measured increases in cell numbers, L5178Y cells also appeared to
      go through the cell cycle with unrepaired hOGG1-recognisable damage. Since
      unrepaired 8-OHdG can give rise to point mutations through G:C-->T:A
      transversions, it was also surprising that mutation could not be detected at the
      Na+/K+ATPase locus as determined by ouabain resistance. Some increases in strand
      breakage could be seen in the Comet assay by increasing the unwinding time, but
      only at highly toxic concentrations and to a much smaller extent than would be
      expected from the magnitude of the other genotoxic responses. It was considered
      unlikely that these anomalous observations were due to the inability of L5178Y
      cells to recognise 8-OHdG because these cells were shown to express mOGG1 and
      have functional cleavage activity at the adducted site. It appears that the
      responses of L5178Y cells to KBrO3 are complex and differ from those induced by
      other oxidising agents.

PMID- 19853638
TI  - Sorting of neuropeptides and neuropeptide receptors into secretory pathways.
AB  - There are two major secretory pathways in neurons, the regulated pathway and the
      constitutive pathway. Neuropeptides and other regulated secretory proteins are
      known to be sorted into large dense-core vesicles of the regulated pathway in the
      trans-Golgi network and are secreted upon stimulus-induced increases in
      intracellular Ca(2+). The newly synthesized cell surface receptors are usually
      sorted into microvesicles of the constitutive pathway and inserted into the
      plasma membrane by spontaneous exocytosis. Small-diameter sensory neurons in
      dorsal root ganglia and pheochromocytoma cells express neuropeptides (e.g.,
      substance P) and several neuropeptide receptors including opioid receptors. The
      mu-opioid receptors are delivered to the cell surface through the constitutive
      pathway, whereas another type of opioid receptor, the delta-opioid receptor, is
      often found in the membrane of large dense-core vesicles and can be inserted into
      the plasma membrane when exocytosis occurs. Recent studies show that sequences
      with opposite electrical polarity within the prohormones of substance P are
      essential for their sorting into large dense-core vesicles. Moreover, the delta
      opioid receptor is sorted into large dense-core vesicles by its interaction with
      protachykinin, a prohormone of substance P. These findings provide insight into
      the molecular mechanisms that determine the sorting and trafficking of
      neuropeptides and neuropeptide receptors in neurons.

PMID- 19853639
TI  - Effect of propofol on the levels of neurotransmitters in normal human brain: a
      magnetic resonance spectroscopy study.
AB  - Though widely used in anesthesia for many years, the mechanism underlying
      propofol anesthesia on human is not clear. Animal studies have already
      demonstrated that propofol functioned mainly by affecting neurotransmitters
      release. In our study, 10 healthy volunteers ranging from 20 to 40 years old were
      enrolled. With the help of target-controlled infusion pump, propofol was
      delivered intravenously. The target-controlled concentration (TCC) of propofol
      was gradually elevated from 0.5 to 3.0 microg/ml (for 6 steps with an increment
      of 0.5 microg/ml). During each step the Observer's Assessment of
      Alertness/Sedation Scale (OAA/S) was performed to evaluate asleep to awake/alert
      status. Magnetic resonance spectroscopy (MRS) was performed to evaluate
      neurotransmitters (choline compounds (Cho), creatine (Cr), glutamate (GLU), gamma
      aminobutyric acid (GABA) and N-acetyl aspartate (NAA)) changes in brains
      following propofol anesthesia. OAA/S scoring showed that when the TCCs of
      propofol were 0, 1.5 and 3.0 microg/ml, the volunteers were in awake, sedative
      and unconscious, respectively. Significantly down-regulated Cho and GLU, but up
      regulated GABA was observed in unconscious state in all the detected regions. NAA
      was decreased in unconscious status only in the hippocampus and thalamus. There
      was no obvious change in Cr levels in any statuses or brain regions. Our results
      indicate that propofol has an impact on the levels of neurotransmitters such as
      NAA, GLU, GABA and Cho in normal human brain. During propofol anesthesia,
      enhancement of inhibition or suppression of excitation may each play key roles in
      different brain regions.

PMID- 19853640
TI  - Progesterone and dexamethasone differentially regulate the IGF-system in glial
      cells.
AB  - IGF-1 is an important factor for myelin synthesis and hence possesses therapeutic
      potential in treating demyelinating disease such as multiple sclerosis. However,
      IGF-1 poorly crosses the blood-brain barrier. In this study, we investigated the
      effects of the sex steroid progesterone and the glucocorticoid dexamethasone on
      regulation of the IGF-system in glial cells. By means of quantitative PCR
      analysis, we demonstrate that progesterone upregulates IGF-1, the type 1 IGF
      receptor and IGFBP-2 in primary rat astrocytes and both IGF-1 and IGFBP-6 in OLN
      93 oligodendroglial progenitor cells. In contrast, dexamethasone showed a
      negative effect on expression of IGF-1, the type 1 IGF receptor and the
      respective IGF binding proteins in both cell types. In oligodendrocytes, the
      differentiation marker CNPase was positively regulated by progesterone and
      negatively regulated by dexamethasone. Further, oligodendroglial cell migration
      was enhanced approximately 4-fold by progesterone. This study implicates
      progesterone as a positive regulator of IGF-system in glial cells and
      demonstrates a further biological function of progesterone in oligodendrocyte
      biology, namely stimulation of progenitor cell migration. Dexamethasone, on the
      other hand, is a negative regulator of the IGF-system in glial cells.

PMID- 19853641
TI  - Proteome analysis reveals candidate markers of disease progression in amyotrophic
      lateral sclerosis (ALS).
AB  - OBJECTIVES: In amyotrophic lateral sclerosis (ALS) the pathological determinants
      of disease progression remain poorly understood. We aimed to identify a
      characteristic CSF protein pattern that could provide new candidate biomarkers of
      disease progression in ALS. METHODS: Using the two-dimensional difference in gel
      electrophoresis (2-D-DIGE), we compared CSF samples from patients with ALS that
      showed a rapid progression of disease (ALS-rp, n=9) over a follow-up time of 2
      years and from patients with ALS that showed a slow progression of disease over
      follow-up (ALS-sl, n=9) 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
      and nephelometry were performed for two candidate proteins on a second cohort of
      patients (n=40). RESULTS: We identified 6 different proteins and their isoforms
      which were all upregulated in ALS-rp as compared to ALS-sl (heat shock protein1,
      alpha-1 antitrypsin, fetuin-A precursor, transferrin, transthyretin (TTR),
      nebulin-related anchoring protein). For Fetuin-A and TTR, our findings could be
      confirmed by quantitative assay. CONCLUSIONS: Fetuin-A and TTR are promising
      candidate markers for disease progression in ALS that warrant further evaluation
      on a larger cohort of patients.

PMID- 19853642
TI  - A role of nitric oxide in neurite outgrowth of neuroblastoma cells triggered by
      mevastatin or serum reduction.
AB  - Neuroblastoma cell lines are commonly used as a model to study neuronal
      differentiation as they retain the capacity to differentiate into a neuronal-like
      phenotype. It is of great medical interest to understand the signalling pathways
      biasing differentiation versus proliferation. Neuroblastoma cells differentiate
      in response to serum reduction or addition of the cholesterol synthesis inhibitor
      mevastatin. The responsible pathways are not well characterized. In Neuro2a
      neuroblastoma cells, we found that mevastatin and serum withdrawal triggered the
      production of nitric oxide (NO). In addition, the differentiation of Neuro2a
      cells and the activation of Akt/PKB triggered by serum withdrawal could be
      blocked by addition of the NO synthetase (NOS) inhibitor l-NAME. Moreover,
      mevastatin and serum withdrawal rapidly increased the expression of the neuronal
      NOS isoform nNOS. However, addition of an NO donor SNP per se did not trigger
      neurite outgrowth. Taken together, we report for the first time a role of NO in
      neurite outgrowth of neuroblastoma cells triggered by mevastatin or serum
      reduction.

PMID- 19853643
TI  - A novel presenilin 1 mutation (Ser169del) in a Chinese family with early-onset
      Alzheimer's disease.
AB  - Early-onset familial Alzheimer's disease (EOFAD) has been associated with
      mutations in three genes, of which presenilin 1 (PSEN1) mutations are the most
      frequent. Here we report a novel PSEN1 mutation in a Chinese family with
      autosomal dominant Alzheimer's disease with an onset age in the early 40s.
      Molecular genetic analysis showed a 507-509delATC mutation at codon 169, leading
      to the deletion of serine in residue 169 (Ser169del). The amnestic presentation
      and absence of other features contrast with the other two mutations at codon 169
      which have been associated with myoclonic jerks and seizures.

PMID- 19853644
TI  - Promoter polymorphisms of the NOS3 gene are associated with hypnotizability
      dependent vascular response to nociceptive stimulation.
AB  - Hypnotizability is associated with a few physiological characteristics also in
      the normal awake state. Differences in flow-mediated dilation (FMD) have been
      observed in subjects with high (Highs) or low (Lows) hypnotizability during
      nociceptive stimulation. FMD is largely due to the nitric oxide (NO) produced by
      vascular endothelium through the activity of NO synthase (eNOS). Endothelial NOS
      is encoded by the NOS3 locus. Aim of this pilot study was to investigate the
      association between genetic polymorphisms of NOS3 involved in NO blood levels and
      hypnotizability. Nine single nucleotide polymorphisms (SNPs) of the NOS3 gene
      were analyzed in the DNA of 24 Highs, 22 Lows, and 61 newborns. Two SNPs,
      rs1800783 (-1474 T/A) and rs2070744 (-786 T/C), located in the upstream and
      promoter region of the gene, respectively, showed significant differences between
      Highs and Lows in allele frequency. Haplotype analysis showed that the newborns
      were in linkage equilibrium for these SNPs, whereas both Highs and Lows showed
      linkage disequilibrium. The A-C haplotype (associated with lower NO availability
      in the general population) was more frequent in Highs, and the T-T haplotype was
      more frequent in Lows. Thus, the lower FMD reduction observed in Highs during
      nociceptive stimulation, which is indicative of higher NO availability, should be
      due to greater efficacy of shear stress-related transcriptional factors and/or to
      lower effects of NOS inhibitory controls. A consequent theoretical proposal
      concerns the possible role of NO in the brain vessels where, in stimulation
      conditions, NO diffusion to the extracellular compartment might be involved in
      hypnotic responding.

PMID- 19853646
TI  - Electroencephalogram functional connectivity between rat hippocampus and cortex
      after pilocarpine treatment.
AB  - The muscarinic agonist pilocarpine has been shown to increase the duration and
      total number of episodes presenting theta rhythm-simultaneously in hippocampus
      and cortex-in rats during the waking states. Theta waves are suggested to be
      involved in the flow of information between hippocampus and cortex during memory
      processes. This work investigates this functional interdependence using the
      spectral and phase synchronization analysis of the electroencephalogram (EEG)
      theta band recorded in these brain structures of rats after pilocarpine
      treatment. Pilocarpine was used at doses devoid of epilepticus-like seizures
      effects in conscious freely moving rats. The results showed that pilocarpine
      administration significantly increased the relative theta power during the waking
      states in the cortex, but not in the hippocampus of rats. Additionally, the EEG
      coherence between the hippocampal EEG theta band and that arising at the frontal
      cortex increased after pilocarpine treatment but only during the waking states.
      This result reveals an increase of the linear correlation between the theta waves
      of these two brain structures after pilocarpine treatment during the waking
      states. Moreover, phase synchronization results showed an effective phase locking
      with non-zero phase difference between hippocampus and frontal cortex theta waves
      that remained after pilocarpine treatment. Therefore, pilocarpine seems to
      reinforce the neural transmission waves from the hippocampus toward the cortex
      during waking. In conclusion, the present EEG study could suggest an effect of
      the muscarinic cholinergic agonist pilocarpine on the hippocampal-cortical
      functional connectivity.

PMID- 19853645
TI  - Targeted drug delivery in pancreatic cancer.
AB  - Effective drug delivery in pancreatic cancer treatment remains a major challenge.
      Because of the high resistance to chemo and radiation therapy, the overall
      survival rate for pancreatic cancer is extremely low. Recent advances in drug
      delivery systems hold great promise for improving cancer therapy. Using
      liposomes, nanoparticles, and carbon nanotubes to deliver cancer drugs and other
      therapeutic agents such as siRNA, suicide gene, oncolytic virus, small molecule
      inhibitor, and antibody has been a success in recent preclinical trials. However,
      how to improve the specificity and stability of the delivered drug using ligand
      or antibody directed delivery represent a major problem. Therefore, developing
      novel, specific, tumor-targeted drug delivery systems is urgently needed for this
      terrible disease. This review summarizes the current progress on targeted drug
      delivery in pancreatic cancer and provides important information on potential
      therapeutic targets for pancreatic cancer treatment.

PMID- 19853647
TI  - Education, occupation, noise exposure history and the 10-yr cumulative incidence
      of hearing impairment in older adults.
AB  - The purpose of this study was to determine the 10-yr cumulative incidence of
      hearing impairment and associations of education, occupation and noise exposure
      history with the incidence of hearing impairment in a population-based cohort
      study of 3753 adults ages 48-92 yr at the baseline examinations during 1993-1995
      in Beaver Dam, WI. Hearing thresholds were measured at baseline, 2.5 yr-, 5 yr-,
      and 10-yr follow-up examinations. Hearing impairment was defined as a pure-tone
      average (PTA)>25 dB HL at 500, 1000, 2000, and 4000 Hz. Demographic
      characteristics and occupational histories were obtained by questionnaire. The 10
      yr cumulative incidence of hearing impairment was 37.2%. Age (5 yr; Hazard Ratio
      (HR)=1.81), sex (M vs W; HR=2.29), occupation based on longest held job
      (production/operations/farming vs others; HR=1.34), marital status (unmarried vs
      married; HR=1.29) and education (<16 vs 16+yr; HR=1.40) were associated with the
      10 yr incidence. History of noisy jobs was not associated with the 10-yr
      incidence of hearing impairment. The risk of hearing impairment was high, with
      women experiencing a slightly later onset. Markers of socioeconomic status were
      associated with hearing impairment, suggesting that hearing impairment in older
      adults may be associated with modifiable lifestyle and environmental factors, and
      therefore, at least partially preventable.

PMID- 19853648
TI  - The antinociceptive activity of Polygonatum verticillatum rhizomes in pain
      models.
AB  - AIM OF THE STUDY: The current study was designed to establish the pharmacological
      rationale for the traditional use of the rhizomes of Polygonatum verticillatum in
      the treatment of painful conditions and as a plant diuretic. MATERIALS AND
      METHODS: The crude methanolic extract of the rhizomes of Polygonatumverticillatum
      (PR) was tested in various established pain models in rodents at 50, 100 and
      200mg/kg i.p. while the diuretic activity was assessed at 300 and 600 mg/kg p.o.
      in rats. RESULTS: PR demonstrated significant reduction (14-72%) in the number of
      writhes induced by acetic acid in a dose-dependent manner. When nociceptive
      threshold was measured in the formalin test, PR strongly attenuated the formalin
      induced flinching behaviour in both phases (6-30% in first phase while 12-72% in
      second phase). Central involvement in the analgesic profile of PR was confirmed
      by the hot plate test, in which PR elicited a significant (P<0.01) analgesic
      activity by increasing latency time. However, an opioid receptor antagonist,
      naloxone (2mg/kg s.c.) strongly antagonized the antinociceptive activity of PR.
      As a plant diuretic, PR showed mild but statistically insignificant diuretic
      activity at 300 mg/kg. The crude extract and solvent fractions of the plant
      contained reasonable quantity of total saponin and alkaloid contents.
      CONCLUSIONS: The mechanisms underlying the analgesic action of PR shows that the
      opioid dependant central mediation has synergistic effect by enforcing the
      peripheral analgesic effects. Interestingly, our findings not only substantiated
      the folk use of the plant as an analgesic but also reported for the first time in
      the whole genus.

PMID- 19853649
TI  - Growth factors and cytokines/chemokines as surrogate biomarkers in cerebrospinal
      fluid and blood for diagnosing Alzheimer's disease and mild cognitive impairment.
AB  - Alzheimer's disease (AD) is a severe chronic neurodegenerative disorder of the
      brain. A probable diagnosis of AD can be obtained by cerebrospinal fluid levels
      of 3 biomarkers: beta-amyloid (1-42), total tau and phospho-tau181. Researchers
      are interested in finding additional biomarkers in CSF to improve the specificity
      and sensitivity of diagnosis, including also other forms of dementia, such as
      mild cognitive impairment (MCI). In addition, less invasive diagnostic methods
      using blood or blood-derived cells are being investigated. This mini-review (in
      concert with the other reviews of this special issue) summarizes the usefulness
      of growth factors and cytokines/chemokines as putative surrogate biomarkers for
      diagnosing AD and MCI in CSF and blood. Briefly, the expression levels of growth
      factors and cytokines/chemokines are very heterogenous, indicating the
      pathological diversity of these diseases. At present, no single growth factor or
      cytokine alone stands out as a useful biomarker for diagnosing AD or MCI.
      However, the combined "patients profile signature" of several selected growth
      factors and/or cytokines/chemokines may allow to diagnose AD and MCI with higher
      selectively and specificity.

PMID- 19853651
TI  - Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human
      lymphocytes from healthy individuals and cancer patients.
AB  - Many patients being treated for cancer use dietary supplements, particularly
      antioxidants, in the hope of reducing the toxicity of chemotherapy or
      radiotherapy. However, clinicians should advise their patients against using
      antioxidant dietary supplements during chemotherapy. Irinotecan (CPT-11) is a
      common chemotherapeutic agent, but it causes side effects, including genotoxicity
      with damages the DNA of blood cells. The aim of this work was to evaluate the
      modulating effect of A, C and E vitamins on genotoxic activity of irinotecan (CPT
      11) and to analyse the efficacy of DNA repair in lymphocytes of both patients
      with diagnosed colorectal carcinoma and healthy individuals in vitro. In healthy
      donors' cells CPT-11 did not exert a strong, genotoxic effect, both in the
      presence of vitamins and without them. In turn, a statistically significant
      increase of DNA migration in the comet tails was noted in patients' lymphocytes.
      The presence of vitamins A, C and E in incubation solutions acted
      synergistically, increasing the level of DNA lesions in cells caused by the
      exposure of the material on tested irinotecan concentrations. Analysis of the
      efficacy of DNA repair, performed after 2h of postincubation, showed the decrease
      of DNA percentage in comet tails in all experimental samples.

PMID- 19853650
TI  - Total and phosphorylated tau protein as biological markers of Alzheimer's
      disease.
AB  - Advances in our understanding of tau-mediated neurodegeneration in Alzheimer's
      disease (AD) are moving this disease pathway to center stage for the development
      of biomarkers and disease modifying drug discovery efforts. Immunoassays were
      developed detecting total (t-tau) and tau phosphorylated at specific epitopes (p
      tauX) in cerebrospinal fluid (CSF), methods to analyse tau in blood are at the
      experimental beginning. Clinical research consistently demonstrated CSF t- and p
      tau increased in AD compared to controls. Measuring these tau species proved
      informative for classifying AD from relevant differential diagnoses. Tau
      phosphorylated at threonine 231 (p-tau231) differentiated between AD and
      frontotemporal dementia, tau phosphorylated at serine 181 (p-tau181) enhanced
      classification between AD and dementia with Lewy bodies. T- and p-tau are
      considered "core" AD biomarkers that have been successfully validated by
      controlled large-scale multi-center studies. Tau biomarkers are implemented in
      clinical trials to reflect biological activity, mechanisms of action of
      compounds, support enrichment of target populations, provide endpoints for proof
      of-concept and confirmatory trials on disease modification. World-wide quality
      control initiatives are underway to set required methodological and protocol
      standards. Discussions with regulatory authorities gain momentum defining the
      role of tau biomarkers for trial designs and how they may be further qualified
      for surrogate marker status.

PMID- 19853652
TI  - Autoschizis of T-cells is induced by the nutritional supplement,
      Cr(III)picolinate.
AB  - In recent times, Cr(III)(picolinate)(3) [Cr(III)(pic)(3)] a nutritional
      supplement, is gaining attention because of its clastogenic and mutagenic
      properties. Earlier studies of ours indicated that Cr(III)(pic)(3) is cytotoxic
      to lymphocytes with ROS and mitochondrial events playing a role in bringing about
      apoptosis. Now, we report that, autoschizis is induced in lymphocytes in a
      concentration and time dependent manner which is confirmed through TEM and SEM.
      Lymphocytes treated with concentrations of 100microM of Cr(III)(pic)(3) exhibit
      features such as cytoplasmic bleb, self excision of cytoplasm, cytoplasmic
      leakage and membrane bound bodies formed from the excised pieces apart from
      apoptosis and necrosis. Though autoschizis has been described in tumor cell lines
      treated with menadione and ascorbate, occurrence of this cell death in normal T
      lymphocytes is reported here. The cellular events that accompany autoschizis are
      found to be increase in intracellular Reactive Oxygen Species (ROS) and
      cytoplasmic lactate dehydrogenase, loss of mitochondrial membrane potential (MMP)
      and depletion of ATP. Further, autoschizis is effected through increases in DNase
      I and DNase II activity with a concomitant decrease in caspase-3 activity which
      leads to a random cleavage of the DNA as demonstrated by a smear like pattern
      after electrophoresis on agarose gel.

PMID- 19853653
TI  - Establishment of yeast reporter assay systems to detect ligands of thyroid
      hormone receptors alpha and beta.
AB  - Thyroid hormones are essential for proper development and differentiation in
      vertebrates. Recently, concern over the disruption of thyroid hormone homeostasis
      by industrial chemicals and environmental pollutants has been spreading. To
      evaluate these chemicals, several bioassays have been developed to detect thyroid
      hormone ligand activity. Nevertheless, a simple and useful assay is required for
      the assessment of an enormous number of environmental chemicals. We established
      yeast reporter assays by expression of full-length thyroid hormone receptor
      (TRalpha or TRbeta) cDNA and of the TR-dependent reporter gene in yeasts. By
      additional introduction of the general coactivator SRC-1 cDNA into the yeasts, a
      higher response to endogenous thyroid hormones, thyroxine (T4), and
      triiodothyronine (T3) was obtained. The EC50 values for T3 were 35 and 1.5nM for
      TRalpha and TRbeta assay yeasts, respectively. We tested four chemicals,
      tetrabromobisphenol A, tetramethylbisphenol A, 2-isopropylphenol, and o-t
      butylphenol, which are suspected to have thyroid hormone-disrupting activity. All
      four chemicals showed agonistic activities in both assay yeasts; however, their
      activities were weak in comparison with endogenous TR ligands. Antagonist
      activities of 2-isopropylphenol and o-t-butylphenol were also found in the
      TRalpha yeast assay. Taken together, these assay yeasts will be powerful tools
      for assessing TR ligand activity of industrial chemicals and environmental
      pollutants.

PMID- 19853655
TI  - Effects of water-filtered infrared A irradiation on human fibroblasts.
AB  - Infrared radiation is a substantial part of the solar energy output reaching the
      earth surface. Therefore, exposure of humans to infrared radiation is common.
      However, whether and how infrared (IR) or infrared A acts on human skin cells is
      still under debate. Recently the generation of reactive oxygen species by water
      filtered infrared A (wIRA) irradiation was postulated. wIRA shows a spectral
      distribution similar to that of solar irradiation at the earth's surface. Thus,
      the need for protection of human skin from both solar- and artificially generated
      infrared A irradiation was concluded. Here we demonstrate that in human dermal
      fibroblasts this reactive oxygen species generation is dependent on heat
      formation by infrared A and can be reproduced by thermal exposure. On the other
      hand wIRA irradiation had no detectable effect if the temperature in the cells
      was kept constant, even if irradiance exceeded the extraterrestrial solar
      irradiance in the IR range by a factor of about 4 and the maximum at noontime in
      the tropics by a factor up to about 6. This could be demonstrated by the
      measurement of oxidant formation using H(2)DCFDA and the determination of protein
      carbonyls. In additional experiments we could show that during thermal exposure
      the mitochondria contribute significantly to oxidant production. Further
      experiments revealed that the major absorbance of infrared is due to absorption
      of the energy by cellular water.

PMID- 19853654
TI  - Behavioral state-dependent reconfiguration of song-related network activity and
      cholinergic systems.
AB  - The song system of oscine songbirds mediates multiple complex perceptive and
      productive behaviors. These discrete behaviors are modulated according to
      external variables such as social context, directed attention and other forms of
      experience. In addition, sleep has been implicated in song learning and song
      maintenance. Changes in behavioral state are associated with complex changes in
      auditory responsiveness and tonic/bursting properties of song system neurons.
      Cholinergic input, principally from the basal forebrain has been implicated in
      some of these state-dependent properties. Cholinergic modulation may affect
      numerous song system nuclei, with in vivo and in vitro studies indicating that a
      major target of cholinergic input is the forebrain nucleus HVC. Within HVC, a
      muscarinic cholinergic system has strong regulatory effects on most neurons, and
      may serve to couple and uncouple circuitry within HVC projecting along the
      premotor pathway with circuitry within HVC projecting along the cortico-basal
      ganglia pathway. These observations begin to describe how neuromodulatory
      regulation in the song system may contribute to learning phenomena.

PMID- 19853656
TI  - Evidence against tetrahydrobiopterin depletion of vascular tissue exposed to
      nitric oxide/superoxide or nitroglycerin.
AB  - Several cardiovascular disorders, including atherosclerosis and tolerance to the
      antianginal drug nitroglycerin (GTN), may be associated with the generation of
      superoxide anions, which react with nitric oxide (NO) to yield peroxynitrite.
      According to a widely held view, oxidation of tetrahydrobiopterin (BH(4)) by
      peroxynitrite causes uncoupling of endothelial NO synthase (eNOS), resulting in
      reduced NO bioavailability and endothelial dysfunction under conditions of
      oxidative stress. In this study we determined the levels of reduced biopterins
      and endothelial function in cultured cells exposed to peroxynitrite and GTN as
      well as in blood vessels isolated from GTN-tolerant guinea pigs and rats. BH(4)
      was rapidly oxidized by peroxynitrite and 3-morpholino sydnonimine (SIN-1) in
      buffer, but this was prevented by glutathione and not observed in endothelial
      cells exposed to SIN-1 or GTN. Prolonged treatment of the cells with 0.1 mM GTN
      caused slow N(G)-nitro-l-arginine-sensitive formation of reactive oxygen species
      without affecting eNOS activity. Endothelial function and BH(4)/BH(2) levels were
      identical in blood vessels of control and GTN-tolerant animals. Our results
      suggest that peroxynitrite-triggered BH(4) oxidation does not occur in
      endothelial cells or GTN-exposed blood vessels. GTN seems to trigger minor eNOS
      uncoupling that is unrelated to BH(4) depletion and without observable
      consequence on eNOS function.

PMID- 19853658
TI  - Mitochondrial dysfunction is a trigger of Alzheimer's disease pathophysiology.
AB  - Mitochondria are uniquely poised to play a pivotal role in neuronal cell survival
      or death because they are regulators of both energy metabolism and cell death
      pathways. Extensive literature exists supporting a role for mitochondrial
      dysfunction and oxidative damage in the pathogenesis of Alzheimer's disease. This
      review discusses evidence indicating that mitochondrial dysfunction has an early
      and preponderant role in Alzheimer's disease. Furthermore, the link between
      mitochondrial dysfunction and autophagy in Alzheimer's disease is also discussed.
      As a result of insufficient digestion of oxidatively damaged macromolecules and
      organelles by autophagy, neurons progressively accumulate lipofuscin that could
      exacerbate neuronal dysfunction. Since autophagy is the major pathway involved in
      the degradation of protein aggregates and defective organelles, an intense
      interest in developing autophagy-related therapies is growing among the
      scientific community. The final part of this review is devoted to discuss
      autophagy as a potential target of therapeutic interventions in Alzheimer's
      disease pathophysiology.

PMID- 19853657
TI  - Mitochondria: a therapeutic target in neurodegeneration.
AB  - Mitochondrial dysfunction has long been associated with neurodegenerative
      disease. Therefore, mitochondrial protective agents represent a unique direction
      for the development of drug candidates that can modify the pathogenesis of
      neurodegeneration. This review discusses evidence showing that mitochondrial
      dysfunction has a central role in the pathogenesis of Alzheimer's, Parkinson's
      and Huntington's diseases and amyotrophic lateral sclerosis. We also debate the
      potential therapeutic efficacy of metabolic antioxidants, mitochondria-directed
      antioxidants and Szeto-Schiller (SS) peptides. Since these compounds
      preferentially target mitochondria, a major source of oxidative damage, they are
      promising therapeutic candidates for neurodegenerative diseases. Furthermore, we
      will briefly discuss the novel action of the antihistamine drug Dimebon on
      mitochondria.

PMID- 19853659
TI  - Matriptase/epithin participates in mammary epithelial cell growth and
      morphogenesis through HGF activation.
AB  - The epithelial-derived, type II transmembrane serine protease matriptase, the
      mouse homologue of which is epithin, has been shown to be involved in epidermal
      differentiation, hair formation, and thymus function. We show in this study that
      epithin/matriptase (Epi/MTP) plays a significant role in mammary epithelial cell
      growth and morphogenesis. Epi/MTP is expressed at low level in the mouse mammary
      epithelium of young animals and it accumulates at the terminal end-bud of the
      growing ducts. The level of Epi/MTP is elevated in the mammary glands at stages
      when epithelial proliferation and modeling occur. It is primarily present in the
      luminal epithelial cells of mouse mammary ducts and lobules. Using an ex vivo
      three-dimensional culture system for mammary epithelial functional assays, we
      show that mammary epithelial growth and morphogenesis in the presence of the
      latent form hepatocyte growth factor (pro-HGF) are blocked either by an inhibitor
      of the Epi/MTP protease activity or by siRNA knockdown of the Epi/MTP expression.
      These studies demonstrate that Epi/MTP participates in mammary epithelial growth
      and modeling through activation of pro-HGF. Our findings reveal an important
      pathway in normal mammary epithelial morphogenesis which may participate in
      breast cancer progression.

PMID- 19853660
TI  - Guidelines to cell engineering for monoclonal antibody production.
AB  - Monoclonal antibodies (mAbs) are currently used for many diagnostic and
      therapeutic applications. The high demand for these biopharmaceuticals has led to
      the development of large-scale manufacturing processes, with productivity
      improvements being mainly achieved by optimization of bioreactor systems.
      However, more recently, the early steps of production, previous to bioreactor
      culture, have been presented as alternative areas where productivity enhancements
      can be achieved. Thus, this review describes the progress made for the
      improvement of productivity in mammalian expression systems for the high
      production of mAbs. Advances in the development of mAb-producing cell lines are
      being made, particularly regarding expression vector design and methods used for
      transfection, with the intent to create a reproducible methodology. Selection of
      the most suitable clones is also a critical step that can be improved, by
      including variables other than the expression level, which is still the common
      practice. Furthermore, strategies of cell engineering, although still mostly
      based on trial-and-error experimentation and not in standard protocols, hold
      great interest to improve cell growth and productivity, as well as product
      quality in the future. Improvements of the initial steps of the production
      process would not only result in cells with higher expression ability, but would
      also speed-up the process development.

PMID- 19853661
TI  - Cortical dopamine dysfunction in symptomatic and premanifest Huntington's disease
      gene carriers.
AB  - We used (11)C-raclopride PET, a marker of D(2) dopamine receptor binding, and
      statistical parametric mapping (SPM) to localise cortical D(2) receptor
      dysfunction in individual Huntington's disease (HD) gene carriers (16 symptomatic
      and 11 premanifest subjects) and assess its clinical significance. 62.5% of
      symptomatic HD patients and 54.5% of premanifest carriers showed cortical
      reductions in D(2) binding. The most frequent decreases in cortical binding in
      individual HD subjects were seen in temporal and frontal areas. Symptomatic HD
      subjects with decreased cortical D(2) binding had worse scores on
      neuropsychological tests assessing attention and executive functions than
      subjects without cortical dopamine dysfunction, notwithstanding comparable
      reduction in striatal D(2) binding and motor disability. Our results indicate
      that cortical dopaminergic dysfunction is common in both symptomatic and
      premanifest HD gene carriers. It is an early event in HD pathophysiology and
      could contribute to the impairment in neuropsychological performance in these
      patients.

PMID- 19853662
TI  - In toxic demyelination oligodendroglial cell death occurs early and is FAS
      independent.
AB  - Oligodendroglial cell death is a frequent phenomenon of many neurological
      diseases, e.g. in demyelinating diseases such as multiple sclerosis (MS). The
      underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic
      demyelination cuprizone model, oligodendroglial cell death and downregulation of
      myelin genes start days after initiation of the cuprizone diet and weeks before
      demyelination is obvious. In early - but not in later - stages, dying
      oligodendrocytes express activated caspase 3, suggesting a switch from classical
      apoptotic pathways to caspase 3-independent mechanisms during the course of the
      cuprizone diet. The expression level of FAS in the corpus callosum, a cell death
      receptor crucial for oligodendroglial cell death in experimental autoimmune
      encephalomyelitis (EAE), correlates with the expression of activated caspase 3 in
      oligodendrocytes. However, mice lacking FAS in oligodendrocytes are not protected
      against cuprizone-induced oligodendroglial cell death, showing that FAS is
      dispensable for oligodendroglial cell death in the cuprizone model.

PMID- 19853663
TI  - Defining the chromatin landscape in demyelinating disorders.
AB  - An intricate network of epigenetic factors regulates cell differentiation by
      modulating the chromatin structure and ultimately affecting gene expression. This
      review describes the chromatin landscape defining oligodendrocyte progenitor
      differentiation during development and remyelination. We shall discuss the
      current knowledge regarding modifications of chromatin components during the
      progression of progenitors into myelinating cells and discuss the potential
      contribution of histone variants, microRNAs, and DNA methylation. We shall also
      briefly address how changes to this chromatin landscape can disturb this natural
      progression and alter the capacity to remyelinate.

PMID- 19853664
TI  - Effective connectivity of neural networks in automatic movements in Parkinson's
      disease.
AB  - Patients with Parkinson's disease (PD) have difficulty in performing learned
      movements automatically. The neural mechanism of this deficiency remains unclear.
      In the current study, we used functional MRI (fMRI) and psychophysiological
      interaction (PPI) methods to investigate the changes in effective connectivity of
      the brain networks when movements become automatic in PD patients and age-matched
      normal controls. We found that during automaticity, the rostral supplementary
      motor area, cerebellum, and cingulate motor area had increased effective
      connectivity with brain networks in PD patients. In controls, in addition to
      these regions, the putamen also had automaticity-related strengthened
      interactions with brain networks. The dorsal lateral prefrontal cortex had more
      connectivity at the novel stage than in the automatic stage in normal subjects,
      but not in PD patients. The comparison of the PPI results between the groups
      showed that the rostral supplementary motor area, cerebellum, and cingulate motor
      area had significantly more increased effective connectivity with several regions
      in normal subjects than in PD. The changes of effective connectivity in some
      areas negatively correlated with the Unified Parkinson's Disease Rating Scale
      (UPDRS). Our findings show that some of the factors related to PD patients having
      difficulty achieving automaticity are less efficient neural coding of movement
      and failure to shift execution of automatic movements more subcortically. The
      changes of effective connectivity become more abnormal as the disorder
      progresses. In addition, in PD, the connections of the attentional networks are
      altered.

PMID- 19853665
TI  - The relationship between structural and functional connectivity: graph
      theoretical analysis of an EEG neural mass model.
AB  - We investigated the relationship between structural network properties and both
      synchronization strength and functional characteristics in a combined neural mass
      and graph theoretical model of the electroencephalogram (EEG). Thirty-two neural
      mass models (NMMs), each representing the lump activity of reasonably large
      groups of interacting excitatory and inhibitory neurons, were reciprocally and
      excitatory coupled using random rewiring as described by Watts and Strogatz.
      Numerical analysis of the network revealed an abrupt transition towards a
      synchronized state as a function of increasing coupling strength alpha.
      Synchronization increased with increasing degree and decreasing regularity of the
      network. Parameters of the functional network showed a diverse dependency on
      structural connectivity: normalized clustering coefficient gamma and path length
      lambda increased with increasing alpha. For sufficiently large alpha, however,
      gamma decreased with increasing rewiring probability p, while lambda increased.
      Hence, a structured functional network exists despite the randomness of the
      underlying structural network. That is, patterns of functional connectivity are
      influenced by patterns of the corresponding structural level but do not
      necessarily agree with those.

PMID- 19853666
TI  - Clostridium difficile testing algorithms: what is practical and feasible?
AB  - There has been renewed interest in the laboratory diagnosis of Clostridium
      difficile infections due in large measure to the increase in both numbers and
      severity of cases of this disease. For the past two decades, enzyme-immunoassays
      (EIAs) for the detection of first C. difficile toxin A and then toxins A and B
      have been the most widely used diagnostic test for diagnosis of C. difficile
      infections. Recently this diagnostic approach has been called into question by
      the recognition that a screening test which detects glutamate dehydrogenase, a
      cell wall antigen of C. difficile, was significantly more sensitive than toxins A
      and B EIAs making it an effective screening test for C. difficile infection.
      Although sensitive, GDH lacks specificity and so if this test was utilized, a
      confirmatory test to differentiate false positives from true positives was
      needed. Studies to date have used cytotoxin neutralization or toxigenic culture
      as confirmatory tests but both of these have their limitations. A testing
      algorithm using rapid immunochromatographic devices for detection of GDH and
      toxins A and B as screening tests will give an accurate test result in
      approximately 90% of specimens within one hour when using cytotoxin
      neutralization as a reference method. For the other 10% of specimens, a third
      test would be needed in the algorithm. This test could be cytotoxin
      neutralization, toxigenic culture, or PCR for toxin or toxin operon genes.

PMID- 19853668
TI  - Antileishmanial effect of cisplatin against murine visceral leishmaniasis.
AB  - Drug development in visceral leishmaniasis is extremely vital as the existing
      therapeutic modalities are plagued by the unwanted twosome of toxicity and drug
      resistance. Antineoplastic drugs have in the past been effective against the
      parasitic infections, for example, miltefosine. Cisplatin is a first-generation
      platinum-containing drug, used in the treatment of various solid tumors. Its in
      vitro antileishmanial effect has already been demonstrated. In the present study,
      the leishmanicidal potential of two doses (0.5mg/kg body weight and 1mg/kg body
      weight) of the drug was studied in BALB/c mice. The antileishmanial effect of the
      drug was revealed by significant reduction in the parasite burden. The infected
      and treated animals were also found to exhibit increased DTH responses. An
      initial transient and reversible increase in levels of SGOT, SGPT, BUN, blood
      urea, creatinine and phosphorus was observed in infected animals treated with
      both doses of the drug. The reduction in parasite load, increase in DTH response
      and various biochemical parameters were more pronounced in animals treated with
      1mg/kg body weight of cisplatin as compared to those treated with 0.5mg/kg body
      weight of the drug. Though some histopathological changes were observed in the
      kidneys of animals treated with 1mg/kg body weight of cisplatin, no such change
      was observed in mice treated with the lower dose. Thus, we have for the first
      time characterized the in vivo effect of cisplatin in murine experimental
      visceral leishmaniasis.

PMID- 19853667
TI  - TNF-alpha inhibitors in asthma and COPD: we must not throw the baby out with the
      bath water.
AB  - Tumor necrosis factor (TNF)-alpha, a pleiotropic cytokine that exerts a variety
      of effects, such as growth promotion, growth inhibition, angiogenesis,
      cytotoxicity, inflammation, and immunomodulation, has been implicated in several
      inflammatory conditions. It plays a significant role in many inflammatory
      diseases of lungs. Given that there is significant literature supporting the
      pathobiologic role of TNF-alpha in asthma, mainly in severe refractory asthma,
      and COPD, TNF-alpha inhibitors (infliximab, golimumab and etanercept) are now
      regarded as the potential new medications in asthma and COPD management. The
      studies reported in literature indicate that TNF-alpha inhibitors are effective
      in a relatively small subgroup of patients with severe asthma, possibly defined
      by an increased TNF axis, but they seem to be ineffective in COPD, although an
      observational study demonstrated that TNF-alpha inhibitors were associated with a
      reduction in the rate of COPD hospitalisation among patients with COPD receiving
      these agents to treat their rheumatoid arthritis. These findings require a smart
      approach because there is still good reason to target TNF-alpha, perhaps in a
      more carefully selected patient group. TNF-alpha treatment should, therefore, not
      be thrown out, or abandoned. Indeed, since severe asthma and COPD are
      heterogeneous diseases that have characteristics that occur with different
      phenotypes that remained poorly characterized and little known about the
      underlying pathobiology contributing to them, it is likely that definition of
      these phenotypes and choice of the right outcome measure will allow us to
      understand which kind of patients can benefit from TNF-alpha inhibitors.

PMID- 19853669
TI  - The expression and distribution of Wnt and Wnt receptor mRNAs during early sea
      urchin development.
AB  - The protein beta-catenin plays a critically important role in establishing axial
      polarity during early animal development. In many organisms, beta-catenin is
      degraded preferentially on one side of the cleavage stage embryo. On the opposite
      side of the embryo, beta-catenin is stabilized and accumulates in the nucleus,
      where it functions in concert with members of the LEF/TCF family to activate the
      transcription of diverse target genes. Genes that are activated by beta-catenin
      play an essential role in the specification of endomesoderm and in the
      establishment of key signaling centers in the early embryo. In several organisms,
      the asymmetric distribution of maternal components of the canonical Wnt pathway
      has been shown to be responsible for the polarized stabilization of beta-catenin.
      In this study, we identified all Wnt and Wnt receptor mRNAs that are present in
      unfertilized sea urchin eggs and early embryos and analyzed their distributions
      along the primary (AV) axis. Our findings indicate that the asymmetric
      distribution of a maternal Wnt or Wnt receptor mRNA is unlikely to be a primary
      determinant of the polarized stabilization of beta-catenin along the AV axis.
      This contrasts sharply with findings in other organisms and points to remarkable
      evolutionary flexibility in the molecular mechanisms that underlie this otherwise
      very highly conserved patterning process.

PMID- 19853670
TI  - Morphine-mediated suppression of phagocytosis.

PMID- 19853671
TI  - Contributions of active site residues to cofactor binding and catalysis of 3alpha
      hydroxysteroid dehydrogenase/carbonyl reductase.
AB  - 3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase reversely catalyzes the
      oxidation of androsterone with NAD(+) to form androstanedione and NADH. In this
      study, we investigated the function of active site residues N86, Y155, and K159
      in NADH binding and catalysis in the reduction of androstanedione, using site
      directed mutagenesis, steady-state kinetics, fluorescence quenching, and
      anisotropy measurements. The N86A, Y155F, and K159A mutant enzymes decreased the
      catalytic constant by 37- to 220-fold and increased the dissociation constant by
      3- to 75-fold, respectively. Binding of NADH with wild-type and mutant enzymes
      caused different levels of fluorescence resonance energy transfer, implying a
      different orientation of nicotinamide ring versus W173. In addition, the enzyme
      bound NADH decreased the fluorescence anisotropy value in the order
      WT>N86A>Y155F>K159A, indicating an increase in the mobility of the bound NADH for
      the mutants. Data suggest that hydrogen bonding with the hydroxyl group of
      nicotinamide ribose by K159 and Y155 is important to maintain the orientation of
      NADH and contributes greatly to the transition-state binding energy to facilitate
      the catalysis. N86 is important for stabilizing the position of K159.
      Substitution of alanine for N86 has a minor effect on NADH binding through K159,
      resulting in a slight increase in the mobility of the bound NADH and decreases in
      affinity and catalytic constant.

PMID- 19853672
TI  - Traditional polypropylene and lightweight meshes in totally extraperitoneal
      inguinal herniorrhaphy.
AB  - BACKGROUND: Placement of a prosthetic mesh is integral to successful totally
      extraperitoneal (TEP) herniorrhaphy. Available meshes have supported the surgical
      efforts well but search for an ideal mesh continues. Post-herniorrhaphy pain is
      an index of patient reported outcomes (PRO). The pain is attributable to balloon
      dissection, cautery, sutures, tackers and prosthesis. Reducing polypropylene
      content of the mesh is associated with attenuated inflammatory response by the
      host and improved compliance and comfort. We report the difference in PROs in TEP
      herniorrhaphy with either heavy polypropylene (PPM) or light weight mesh (LWM)
      being used for the repair. PATIENTS AND METHODS: From June 2004 to December 2005,
      consecutive candidates for TEP herniorrhaphy were enrolled for this prospective
      study with an informed consent and compliance to Ethics guidelines. They were
      operated under general anesthesia (GA) on a day care basis using either PPM or
      LWM meshes as per the patient's choice. Operative and postoperative PRO were
      statistically analyzed by an independent doctor using the Microsoft Office Excel
      2003. RESULTS: One hundred fourteen (84 PPMs and 30 LWMs) TEP herniorrhaphies
      were performed under GA on 57 male patients without any exclusion, on a day care
      basis. There was no technical difficulty, operative complications, conversion or
      prolonged hospital stay in either group. Patients of LWM reported better outcome
      in regards to pain, NSAID usage, seroma and recurrence. All patients of LWM
      reported an earlier return to activity. CONCLUSION: Light weight meshes result in
      comparatively better "patient reported outcomes" in TEP inguinal herniorrhaphy as
      compared to heavy polypropylene meshes.

PMID- 19853674
TI  - Epigenetic regulation of latent Epstein-Barr virus promoters.
AB  - Epigenotypes are modified cellular or viral genotypes that differ in
      transcriptional activity in spite of having an identical or nearly identical DNA
      sequence. Restricted expression of latent, episomal Epstein-Barr virus (EBV)
      genomes is a consequence of a series of epigenetic modifications. In tight
      latency, there is no virus production (lytic viral replication, associated with
      the expression of all viral genes), and only a limited set of viral promoters is
      activated in a host-cell-dependent manner. The latent EBV promoters control the
      expression of growth-transformation-associated viral genes. The role of major
      epigenetic mechanisms in the regulation of latent EBV promoters is variable. DNA
      methylation contributes to silencing of Wp and Cp (alternative promoters for
      transcripts coding for nuclear antigens EBNA 1-6) and LMP1p, LMP2Ap and LMP2Bp
      (promoters for transcripts encoding transmembrane proteins). DNA methylation does
      not control, however, Qp (a promoter for EBNA1 transcripts only) in B
      lymphoblastoid cell lines (LCLs, immortalized by EBV in vitro), although in vitro
      methylated Qp-reporter gene constructs are silenced. The invariably unmethylated
      Qp is probably switched off by binding of a repressor protein in LCLs. Histone
      modifications may also contribute to the regulation of latent EBV promoters
      because the active Cp, Qp and LMP2Ap promoters that are marked by strong binding
      of cellular regulatory proteins are located on "acetylation islands" enriched in
      diacetylated histone H3 and tetraacetylated histone H4. We speculate that binding
      of the chromatin insulator protein CTCF to 3 distinct sites (within, close to and
      far from the matrix attachment region) may contribute to the three-dimensional
      organization of the viral episomes. We also raise the point that latent EBV
      episomes may relocate to new nuclear subcompartments before the start of lytic
      EBV replication. We propose that a similar relocation of EBV episomes may result
      in a promoter switch (from Qp to Cp) due to the access of Cp to a B-lymphoblast
      specific transcription factory when in vitro cultivated Burkitt's lymphoma cells
      undergo a phenotypic drift.

PMID- 19853675
TI  - Determination of the core promoter regions of the Saccharomyces cerevisiae RPS3
      gene.
AB  - Ribosomal protein genes (RPG), which are scattered throughout the genomes of all
      eukaryotes, are subjected to coordinated expression. In yeast, the expression of
      RPGs is highly regulated, mainly at the transcriptional level. Recent research
      has found that many ribosomal proteins (RPs) function in multiple processes in
      addition to protein synthesis. Therefore, detailed knowledge of promoter
      architecture as well as gene regulation is important in understanding the
      multiple cellular processes mediated by RPGs. In this study, we investigated the
      functional architecture of the yeast RPS3 promoter and identified many putative
      cis-elements. Using beta-galactosidase reporter analysis and EMSA, the core
      promoter of RPS3 containing UASrpg and T-rich regions was corroborated. Moreover,
      the promoter occupancy of RPS3 by three transcription factors was confirmed.
      Taken together, our results further the current understanding of the promoter
      architecture and trans-elements of the Saccharomyces cerevisiae RPS3 gene.

PMID- 19853673
TI  - Chromatin organization of gammaherpesvirus latent genomes.
AB  - The gammaherpesviruses are a subclass of the herpesvirus family that establish
      stable latent infections in proliferating lymphoid and epithelial cells. The
      latent genomes are maintained as multicopy chromatinized episomes that replicate
      in synchrony with the cellular genome. Importantly, most of the episomes do not
      integrate into the host chromosome. Therefore, it is essential that the viral
      "minichromosome" establish a chromatin structure that is suitable for gene
      expression, DNA replication, and chromosome segregation. Evidence suggests that
      chromatin organization is important for each of these functions and plays a
      regulatory role in the establishment and maintenance of latent infection. Here,
      we review recent studies on the chromatin organization of the human
      gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated
      herpesvirus (KSHV). We discuss the potential role of viral origins of DNA
      replication and viral encoded origin-binding proteins like EBNA1 and LANA in
      establishment of viral chromosome organization during latent infection. We also
      discuss the roles of host cell factors, like CTCF and cohesins, that contribute
      to higher-order chromosome structures that may be important for stable gene
      expression programs during latent infection in proliferating cells.

PMID- 19853676
TI  - Osteoarthritic cartilage chondrocytes alter subchondral bone osteoblast
      differentiation via MAPK signalling pathway involving ERK1/2.
AB  - Osteoarthritic subchondral bone is characterized by abnormal bone density and
      enhanced production of bone turnover markers, an indication of osteoblast
      dysfunction. Several studies have proposed that pathological changes in articular
      cartilage influence the subchondral bone changes, which are typical of the
      progression of osteoarthritis; however, direct evidence of this has yet to be
      reported. The aim of the present study was to investigate what effects articular
      cartilage cells, isolated from normal and osteoarthritic joints, may have on the
      subchondral bone osteoblast phenotype, and also the potential involvement of the
      mitogen activated protein kinase (MAPK) signalling pathway during this process.
      Our results suggest that chondrocytes isolated from a normal joint inhibited
      osteoblast differentiation, whereas chondrocytes isolated from an osteoarthritic
      joint enhanced osteoblast differentiation, both via a direct and indirect cell
      interaction mechanisms. Furthermore, the interaction of subchondral bone
      osteoblasts with osteoarthritic chondrocyte conditioned media appeared to
      significantly activate ERK1/2 phosphorylation. On the other hand, conditioned
      media from normal articular chondrocytes did not affect ERK1/2 phosphorylation.
      Inhibition of the MAPK-ERK1/2 pathways reversed the phenotype changes of
      subchondral bone osteoblast, which would otherwise be induced by the conditioned
      media from osteoarthritic chondrocytes. In conclusion, our findings provide
      evidence that osteoarthritic chondrocytes affect subchondral bone osteoblast
      metabolism via an ERK1/2 dependent pathway.

PMID- 19853677
TI  - Distraction osteogenesis induces endothelial progenitor cell mobilization without
      inflammatory response in man.
AB  - INTRODUCTION: Distraction osteogenesis (DO) is a unique postnatal bone formation
      process, which is characterized by a profuse increase in vascularization.
      Recently endothelial progenitor cells (EPCs) have been reported to circulate in
      substantial numbers under physiologic conditions and to contribute to bone
      regeneration. The authors investigated EPC mobilization in patients undergoing
      limb lengthening. MATERIALS AND METHODS: Thirteen of 24 consecutive patients who
      underwent limb-lengthening procedures on weight-bearing long bones (femur and
      tibia) were included in this study. Peripheral blood samples were taken at four
      different time points from each patient, that is, before operation (pre-Op), 2 or
      3 days after osteotomy (early-PO), before the start of distraction (pre-Dist),
      and at 7 to 14 days after the start of distraction (during-Dist). Numbers of
      leukocytes and levels of plasma C-reactive protein (CRP) were determined. After
      isolating mononuclear cells (MNCs) by centrifugation, we performed FACS analysis
      on freshly isolated MNCs using antibodies to the cell surface markers; CD34,
      CD133, vascular endothelial growth factor receptor 2 (VEGFR2), and alkaline
      phosphatase. MNCs were also cultured in endothelial cell growth medium and
      numbers of EPC colony-forming units were counted. Plasma levels of EPC-mobilizing
      cytokines, such as, VEGF, SDF-1, and MCP-1, were determined by ELISA. RESULTS:
      Numbers of leukocytes and CRP plasma levels increased significantly during the
      early-PO period (p<0.01) but were maintained within normal range in the during
      Dist period. FACS analysis of freshly isolated MNCs showed that EPC-enriched cell
      fractions increased after distraction, but that alkaline phosphatase-positive
      cell numbers were unchanged. Numbers of EPC colony-forming units significantly
      increased in the during-Dist period (p<0.01). Plasma levels of VEGF and SDF-1
      significantly increased in the during-Dist period (p<0.05). In femoral
      lengthening patients whose healing index was less than 30 days/cm, the number of
      CFUs was 46.8 in the during-Dist period, whereas it was 12.7 in patients whose
      healing index was more than 30 days/cm (p=0.088). CONCLUSIONS: This study
      demonstrates a mobilization of EPC population during distraction osteogenesis in
      human limb-lengthening patients. Distraction strain provoked increases in the
      plasma levels of EPC-mobilizing cytokines, such as, VEGF and SDF-1. These
      findings suggest a possibility that therapeutical approaches which modulate EPC
      mobilization may speed bone healing by angiogenesis-osteogenesis coupling during
      distraction osteogenesis.

PMID- 19853678
TI  - The effect of risedronate on hip structural geometry in chemotherapy-induced
      postmenopausal women with or without use of aromatase inhibitors: a 2-year trial.
AB  - INTRODUCTION: Osteoporosis is a major health problem for postmenopausal women.
      Adjuvant hormonal therapy with aromatase inhibitors (AIs) in postmenopausal
      breast cancer patients further worsens bone loss. Bisphosphonates are able to
      prevent AI-induced bone loss, but limited data exists on their effect on bone
      structure. Our objectives were to (1) examine the impact of AIs and no-AIs on hip
      structural geometry (HSA) of chemotherapy-induced postmenopausal women, and (2)
      determine if oral bisphosphonates could affect these changes. METHODS: This is a
      sub-analysis of a 2-year double-blind randomized trial of 67 women with
      nonmetastatic breast cancer, newly postmenopausal following chemotherapy (up to 8
      years), who were randomized to risedronate, 35 mg once weekly (RIS) and placebo
      (PBO). Many women changed their cancer therapy from a no-AI to an AI during the
      trial. Outcomes were changes in Beck's HSA-derived BMD and structural parameters.
      RESULTS: Eighteen women did not receive adjuvant hormone therapy, while 41 women
      received other therapy and 8 received AIs at baseline distributed similarly
      between RIS and PBO. Women on AIs and PBO were found to have the lowest BMD and
      indices. RIS improved BMD and several HSA indices at the intertrochanteric site
      in women regardless of their hormonal therapy, but most improvement was observed
      in women who were not on AIs (all p< or =0.05 except buckling ratio). Changes at
      the narrow neck and femoral shaft were similar. CONCLUSION: The use of AIs
      appears to lead to lower HSA-derived BMD and hip structural indices as compared
      to women on no or non-AI therapy in chemotherapy-induced postmenopausal breast
      cancer patients. Preventive therapy with once weekly oral risedronate maintains
      structural, skeletal integrity independently of the use of or type of adjuvant
      therapy.

PMID- 19853679
TI  - Alphavirus replicon particle vaccines developed for use in humans induce high
      levels of antibodies to influenza virus hemagglutinin in swine: proof of concept.
AB  - A propagation-defective, single-cycle, alphavirus replicon particle (RP) system
      was used to produce two vaccines against human influenza virus A/Wyoming/03/2003
      (H3N2). One vaccine was prepared from Venezeulan equine encephalitis virus (VEEV)
      strain 3014 and the other from VEEV strain TC-83. Both vaccines induced high
      antibody titers to the influenza hemagglutinin (HA) protein and illustrated the
      potential of using alphavirus RP influenza vaccines in swine.

PMID- 19853681
TI  - Modulation of inter-vaccination interval to avoid antigenic competition in
      multivalent footrot (Dichelobacter nodosus) vaccines in sheep.
AB  - Virulent footrot is a significant disease of sheep in most sheep farming
      countries; a strain/serogroup of the anaerobic bacterium Dichelobacter nodosus is
      the essential transmitting agent. Commercial multivalent footrot vaccines
      containing nine fimbrial serogroups (A through I) of D. nodosus produce
      relatively low and short term antibody responses due to antigenic competition, in
      contrast to higher and longer responses provided by monovalent or bivalent
      vaccines. The latter were important components of successful eradication programs
      for endemic footrot caused by either one or two serogroups of D. nodosus in
      Nepal, Bhutan, and several flocks in Australia. However, the presence of up to
      six serogroups in some Australian flocks and the use of an annual bivalent
      vaccination regime to progressively eradicate serogroups would require a long
      term program. In this study we report the results of a sequential vaccination
      trial testing different time intervals between different bivalent vaccinations.
      Intervals of 12, 9, 6, 3 and 0 months were tested. The 1st vaccination was with
      recombinant fimbrial antigens for serogroups A and B while the 2nd vaccination
      was with D and E. There were no significant differences between the antibody
      responses for time intervals of 3, 6, 9 and 12 months whereas there was a reduced
      response when sheep were vaccinated with two bivalent vaccines (four antigens)
      concurrently, indicating antigenic competition. Therefore an inter-vaccination
      interval of 3 months can be applied between two different bivalent vaccines
      without detrimental impact on the humoral immune responses to the various
      fimbrial antigens of D. nodosus. These results could have wider applications in
      vaccination against diseases caused by multivalent or multistrain microbes.

PMID- 19853680
TI  - Double-blind, randomized, placebo-controlled Phase I Clinical Trial of the
      therapeutical antituberculous vaccine RUTI.
AB  - A Phase I interventional Clinical Trial was performed with a potential
      tuberculosis vaccine, based on detoxified cellular fragments of M. tuberculosis,
      named RUTI. The objective was to evaluate the safety profile and T-cell immune
      responses over a 6-month period following subcutaneous inoculation. The double
      blind, randomized and placebo-controlled trial was conducted in healthy
      volunteers, all recruited at one site. RUTI, at each of the four tested doses,
      starting from 5microg and going up to 200microg, and placebo were inoculated to
      groups of 4 and 2 volunteers respectively, consecutively. RUTI appeared to be
      well tolerated as judged by local and systemic clinical evaluation, though
      vaccine dose dependent local adverse reactions were recorded. T-cell responses of
      blood lymphocytes to PPD and a number of antigen subunits were elevated, when
      compared with controls subjects. These results support the feasibility of future
      evaluation, to be targeted at subjects with latent tuberculosis infection (LTBI).

PMID- 19853682
TI  - Evaluation of live-attenuated Salmonella vaccines expressing Campylobacter
      antigens for control of C. jejuni in poultry.
AB  - Campylobacter jejuni is a zoonotic bacterial pathogen of worldwide importance. It
      is estimated that 460,000 human infections occur in the United Kingdom per annum
      and these involve acute enteritis and may be complicated by severe systemic
      sequelae. Such infections are frequently associated with the consumption of
      contaminated poultry meat and strategies to control C. jejuni in poultry are
      expected to limit pathogen entry into the food chain and the incidence of human
      disease. Toward this aim, a total of 840 Light Sussex chickens were used to
      evaluate a Salmonella enterica serovar Typhimurium DeltaaroA vaccine expressing
      the C. jejuni amino acid binding protein CjaA as a plasmid-borne fusion to the C
      terminus of fragment C of tetanus toxin. Chickens were given the vaccine at 1-day
      old and two weeks later by oral gavage, then challenged after a further two weeks
      with C. jejuni. Across six biological replicates, statistically significant
      reductions in caecal C. jejuni of c. 1.4log(10) colony-forming units/g were
      observed at three and four weeks post-challenge relative to age-matched
      unvaccinated birds. Protection was associated with the induction of CjaA-specific
      serum IgY and biliary IgA. Protection was not observed using a vaccine strain
      containing the empty plasmid. Vaccination with recombinant CjaA subcutaneously at
      the same intervals significantly reduced the caecal load of C. jejuni at three
      and four weeks post-challenge. Taken together these data imply that responses
      directed against CjaA, rather than competitive or cross-protective effects
      mediated by the carrier, confer protection. The impact of varying parameters on
      the efficacy of the S. Typhimurium DeltaaroA vaccine expressing TetC-CjaA was
      also tested. Delaying the age at primary vaccination had little impact on
      protection or humoral responses to CjaA. The use of the parent strain as carrier
      or changing the attenuating mutation of the carrier to DeltaspaS or DeltassaU
      enhanced the protective effect, consistent with increased invasion and
      persistence of the vaccine strains relative to the DeltaaroA mutant. Expression
      in the DeltaaroA strain of a TetC fusion to Peb1A, but not TetC fusions to GlnH
      or ChuA, elicited protection against intestinal colonisation by C. jejuni that
      was comparable to that observed with the TetC-CjaA fusion. Our data are rendered
      highly relevant by use of the target host in large numbers and support the
      potential of CjaA- and Peb1A-based vaccines for control of C. jejuni in poultry.

PMID- 19853683
TI  - Atrial fibrillation and quality of life.

PMID- 19853685
TI  - Management of ST-segment elevation myocardial infarction: Comparison of the
      updated guidelines from North America and Europe.
AB  - The American College of Cardiology/American Heart Association and the European
      Society of Cardiology each recently published updated guidelines for management
      of patients with acute ST elevation myocardial infarction. In this article, we
      highlight the most important new recommendations, review their supporting data,
      and describe differences between the guidelines. Key aspects of these updates
      include detailed guidance regarding the selection of a reperfusion strategy and
      the incorporation of newer adjunctive antithrombotic agents. Both new guidelines
      suggest caution in the administration of intravenous beta-blockers, avoidance of
      nonsteroidal anti-inflammatory agents, and support a more aggressive approach to
      secondary risk factor management. The 2 guidelines have some nuanced differences
      as well as some recommendations that are unique to each guideline. They present
      different levels of support for the 4 available adjunctive parenteral
      anticoagulants, vary in their endorsement of routine elective coronary
      angiography after fibrinolysis, and cite different targets for low density
      lipoprotein long-term. Major unique recommendations include the American College
      of Cardiology/American Heart Assocaition's emphasis of a stepped approach to
      analgesia in patients with musculoskeletal pain beginning with acetaminophen or
      aspirin and a lower target international normalized ratio in patients receiving
      warfarin, aspirin, and clopidogrel. Meanwhile, unique recommendations in the
      European Society of Cardiology guidelines include measures to prevent/treat
      microvascular obstruction and reperfusion injury associated with percutaneous
      coronary intervention and greater emphasis on maintaining eugylcemia. As these
      guidelines represent an evidence based approach, health care providers should
      become familiar with the new data and the resultant updated recommendations to
      ensure optimal treatment of their patients with ST-elevation myocardial
      infarction.

PMID- 19853686
TI  - Magnitude and consequences of missing the acute infarct-related circumflex
      artery.
AB  - Emergent reperfusion strategies are integral to providing optimal patient
      outcomes in the setting of acute coronary artery occlusion. ST-segment elevation
      on the surface 12-lead electrocardiogram, although specific as a surrogate
      marker, is insensitive to acute posterior circulation coronary artery occlusion.
      Studies of non-ST-segment elevation acute coronary syndrome consistently identify
      patients who have epicardial vessel occlusion at the time of initial angiography,
      which is usually delayed for hours or days after the initial presentation. In
      addition, studies of ST-segment elevation myocardial infarction often divulge a
      disparity in identification of the infarct-related artery, with an
      underrepresentation of the left circumflex artery. Taken together, it is likely
      that many patients with left circumflex artery occlusion are "missed" during the
      early phases of myocardial infarction due to the electrocardiographically silent
      nature of the posterior territory, resulting in delayed myocardial salvage and
      worse cardiovascular outcomes. In this review, we report on the magnitude of
      missed left circumflex infarction and the consequences of this delay in
      diagnosis. We review the electrocardiographic findings of left circumflex
      occlusion and discuss strategies to enhance early identification. Heightened
      awareness of this clinical scenario and the available methods to avoid missing
      this elusive diagnosis are imperative in our quest to further improve the
      outcomes of patients with acute myocardial infarction.

PMID- 19853687
TI  - Design and rationale of the WOEST trial: What is the Optimal antiplatElet and
      anticoagulant therapy in patients with oral anticoagulation and coronary StenTing
      (WOEST).
AB  - BACKGROUND: Long-term oral anticoagulant treatment is obligatory in patients
      (class I) with mechanical heart valves and most patients with atrial
      fibrillation. When these patients undergo percutaneous coronary intervention with
      stenting, there is also an indication for treatment with aspirin and clopidogrel.
      However, triple therapy is known to increase the risk of bleeding complications.
      Unfortunately, there are no prospective data available to resolve this issue.
      Nevertheless, it all comes down to finding the ideal therapy in patients with
      indications of both chronic anticoagulation therapy and percutaneous intervention
      to prevent thrombotic complications (eg, stent thrombosis) without increasing the
      risk of bleeding. OBJECTIVES: This prospective randomized multicenter study will
      assess the hypothesis that after percutaneous coronary intervention with stent
      implantation in patients on oral anticoagulant therapy, the combination of oral
      anticoagulation therapy and clopidogrel 75 mg/d reduces the risk of bleeding and
      is not inferior to triple therapy treatment with respect to the prevention of
      thrombotic complications. DESIGN: Multicenter, international, open-label
      randomized trial evaluating triple therapy (clopidogrel + oral anticoagulants +
      aspirin) in patients with an indication for oral anticoagulants who undergo
      coronary stenting versus the combination of oral anticoagulants and clopidogrel.
      The primary outcome is the combination of TIMI and GUSTO minor and major bleeding
      up to 30 days and 1 year. The secondary outcomes are major adverse cardiac
      events. The sample size is 496. CONCLUSIONS: No prospective randomized study has
      yet addressed the issue of optimal antiplatelet therapy in patients with chronic
      oral anticoagulant therapy undergoing coronary stenting. Therefore, the WOEST
      trial will help to define new guidelines for patients with indication for chronic
      anticoagulation who need coronary stenting.

PMID- 19853688
TI  - Rationale and design of the Duke Electrophysiology Genetic and Genomic Studies
      (EPGEN) biorepository.
AB  - BACKGROUND: Disturbances in cardiac rhythm can lead to significant morbidity and
      mortality. Many arrhythmias are known to have a heritable component, but the
      degree to which genetic variation contributes to disease risk and morbidity is
      poorly understood. METHODS AND RESULTS: The EPGEN is a prospective single-center
      repository that archives DNA, RNA, and protein samples obtained at the time of an
      electrophysiologic evaluation or intervention. To identify genes and molecular
      variants that are associated with risk for arrhythmic phenotypes, EPGEN uses
      unbiased genomic screening; candidate gene analysis; and both unbiased and
      targeted transcript, protein, and metabolite profiling. To date, EPGEN has
      successfully enrolled >1,500 subjects. The median age of the study population is
      62.9 years; 35% of the subjects are female and 21% are black. To this point, the
      study population has been composed of patients who had undergone defibrillator
      (implantable cardioverter-defibrillator or cardiac resynchronization therapy
      defibrillator) implantation (45%), electrophysiology studies or ablation
      procedures (35%), and pacemaker implantation or other procedures (20%). The
      cohort has a high prevalence of comorbidities, including diabetes (33%),
      hypertension (73%), chronic kidney disease (26%), and peripheral vascular disease
      (13%). CONCLUSIONS: We have established a biorepository and clinical database
      composed of patients with electrophysiologic diseases. EPGEN will seek to (1)
      improve risk stratification, (2) elucidate mechanisms of arrhythmogenesis, and
      (3) identify novel pharmacologic targets for the treatment of heart rhythm
      disorders.

PMID- 19853689
TI  - Design and rationale of the Evaluation of M118 IN pErcutaNeous Coronary
      intErvention (EMINENCE) trial.
AB  - BACKGROUND: Currently recommended anticoagulant agents used in the setting of
      percutaneous coronary intervention (PCI) inhibit, with varying degrees of
      intensity, 2 critical targets (factor Xa and/or IIa) of the coagulation cascade,
      yet they carry significant limitations. M118-a novel, rationally engineered
      heparin-provides consistent anti-Xa and anti-IIa activity with a constant anti
      Xa:anti-IIa ratio over time. M118 also combines the desired anticoagulant effects
      of unfractionated heparin with the beneficial attributes of low-molecular-weight
      heparin, and may represent the next generation of heparin therapy in patients
      diagnosed with acute coronary syndrome. STUDY DESIGN: The EMINENCE trial is a
      prospective, randomized, open-label, multicenter phase 2 study that will evaluate
      the safety and feasibility of M118 as an anticoagulant versus unfractionated
      heparin in subjects with stable coronary artery disease undergoing PCI. The
      primary end point of the study will be the combined incidence of clinical events
      defined as the composite of 30-day death, myocardial infarction, repeat
      revascularization, catheter thrombus, stroke, thrombocytopenia, bailout use of
      glycoprotein IIb/IIIa inhibitors, and major or minor bleeding. CONCLUSION: The
      EMINENCE trial will assess the safety and feasibility of M118 as an anticoagulant
      in the setting of PCI and will provide important information to determine the
      appropriate therapeutic range of activated clotting time for M118 and the
      appropriate dose or doses to be explored in a phase 3 clinical trial.

PMID- 19853690
TI  - High-intensity interval training may reduce in-stent restenosis following
      percutaneous coronary intervention with stent implantation A randomized
      controlled trial evaluating the relationship to endothelial function and
      inflammation.
AB  - BACKGROUND: High-intensity interval training has been shown to be superior to
      moderate continuous exercise training in improving exercise capacity and
      endothelial function in patients with coronary artery disease. The objective of
      this study was to evaluate this training model on in-stent restenosis following
      percutaneous coronary intervention for stable or unstable angina. METHODS AND
      RESULTS: We prospectively randomized 40 patients after percutaneous coronary
      intervention with implantation of a bare metal stent (n = 30) or drug eluting
      stent (n = 32) to a 6-month supervised high-intensity interval exercise training
      program (n = 20) or to a control group (n = 20). At six months, restenosis,
      measured as in-segment late luminal loss of the stented coronary area, was
      smaller in the training group 0.10 (0.52) mm compared to the control group 0.39
      (0.38) mm (P = .01). Reduction of late luminal loss in the training group was
      consistent with both stent types. Peak oxygen uptake increased in the training
      and control group by 16.8% and 7.8%, respectively (P < .01). Flow-mediated
      dilation improved 5.2% (7.6) in the training group and decreased -0.1% (8.1) in
      the control group (P = .01). Levels of high-sensitivity C-reactive protein
      decreased by -0.4 (1.1) mg/L in the training group and increased by 0.1 (1.2)
      mg/L in the control group (P = .03 for trend). CONCLUSIONS: Regular high
      intensity interval exercise training was associated with a significant reduction
      in late luminal loss in the stented coronary segment. This effect was associated
      with increased aerobic capacity, improved endothelium function, and attenuated
      inflammation.

PMID- 19853691
TI  - Reporting and representation of race/ethnicity in published randomized trials.
AB  - BACKGROUND: Although adequate representation of specific subgroups (eg, women and
      the elderly) in randomized controlled trials (RCTs) has been under intense
      scrutiny, there are few data on representation by race. METHODS: Using all RCTs
      cited by the 2007 American Heart Association guidelines for cardiovascular
      disease prevention in women (although trials were included whether or not there
      were female participants), we explored the extent to which information on race
      was reported in the baseline characteristics. Race/ethnicity categories were
      whites, blacks, Asians, Hispanics, and "others." RESULTS: Overall, 156 trials
      were analyzed. Demographic data on race/ethnicity were reported in 55 (35%)
      trials and increased significantly over time (1970s, 12.5%; 1980s, 25%; 1990s,
      30.5%; 2000s, 46.2%; P for trend = .011). Among the 55 trials reporting any
      race/ethnicity information, trial inclusion of whites, blacks, Asians, Hispanics,
      and "others" was reported in 27%, 13%, 14%, 5%, and 10% of trials, respectively,
      and increased over time (P for trend < .05 for all). Trials enrolling subjects
      only in the United States or globally, including the US, were more likely to
      report race composition than trials that included no US sites (US only 64% vs
      global 62% vs non-US 21%, P < .01). Industry- and federal/foundation-funded RCTs
      reported race with similar frequency (industry 36% vs federal 34% vs both 24%, P
      = .44). When we isolated our analyses to trials that were funded by the National
      Institutes of Health, 12 (67%) of 18 RCTs reported race/ethnicity as a baseline
      characteristic. CONCLUSION: Although reporting the race/ethnic composition of
      study populations is increasing over time, two thirds of all RCTs supporting a
      recent American Heart Association () guideline failed to publish any information
      on race. A necessary first requirement in translating RCT evidence to patients of
      all races is information regarding racial demographics. Such information should
      be strongly encouraged in future publications.

PMID- 19853692
TI  - Comparative trends in guidelines adherence among patients with non-ST-segment
      elevation acute coronary syndromes treated with invasive versus conservative
      management strategies: Results from the CRUSADE quality improvement initiative.
AB  - BACKGROUND: Prior studies have demonstrated differences in adherence to non-ST
      segment elevation acute coronary syndromes (NSTE ACS) guidelines-recommended
      therapies among patients managed conservatively without cardiac catheterization
      compared with those managed invasively. We evaluated the degree of yearly change
      in use of guidelines-recommended therapies for patients with NSTE ACS in CRUSADE
      stratified by use of cardiac catheterization and revascularization procedures.
      METHODS: We analyzed data from 138,714 high-risk patients with NSTE ACS treated
      at 547 hospitals during the first 4 years of the CRUSADE initiative. Patients
      were categorized as no cardiac catheterization (29% of the total population),
      cardiac catheterization without revascularization (21%), percutaneous coronary
      intervention (40%), and coronary artery bypass graft surgery (11%). Composite
      guidelines adherence scores were used to compare yearly changes in use of
      guidelines-recommended therapies among the groups. RESULTS: Although guidelines
      adherence improved in all 4 groups each year and was consistently highest in the
      percutaneous coronary intervention group, the adjusted yearly increase in the use
      of acute guidelines-recommended medications was highest in the no cardiac
      catheterization group, and the adjusted yearly increase in the use of discharge
      medications was highest in the coronary artery bypass graft surgery group.
      CONCLUSIONS: Improvements in the use of guidelines-recommended therapies were
      seen among all patients with NSTE ACS in CRUSADE over a 4-year period regardless
      of management strategy, and the trajectory of improvement in acute care was
      greatest in patients managed conservatively.

PMID- 19853693
TI  - Contribution of angiographic and electrocardiographic parameters of reperfusion
      to prediction of mortality and morbidity after acute ST-elevation myocardial
      infarction: Insights from the Assessment of Pexelizumab in Acute Myocardial
      Infarction trial.
AB  - BACKGROUND: Reperfusion with primary percutaneous intervention (PCI) in ST
      segment elevation myocardial infarction leads to improved clinical outcomes. The
      contribution angiographic vs electrocardiographic reperfusion parameters confer
      on prognosis is unclear. METHODS: A prespecified subset of the APEX-AMI trial
      patients was analyzed by independent angiographic and electrocardiographic core
      laboratories (n = 1,018). Angiographic reperfusion after PCI and
      electrocardiogram 30 minutes post-PCI were assessed. RESULTS: Of the 941 patients
      in the angiographic substudy, 796 (85%) attained post-PCI Thrombolysis In
      Myocardial Infarction (TIMI) flow 3 and 852 (91%) had TIMI Myocardial Perfusion
      Grade (TMPG) 2/3. There were 664 (71%) patients with residual ST elevation (ST-E)
      <2 mm. Ninety-day mortality and death/CHF/shock were lower in patients with TIMI
      flow 3 vs <3 (1.9% vs 6.2%, P = .002; 5.8% vs 10.4%, P = .044) and those with
      TMPG 2/3 vs 0/1 (2.0% vs 7.9%, P = .001; 6.0% vs 11.9%, P = .028). Patients with
      residual ST-E <2 mm had similar rates of mortality as those with > or =2 mm (2.3%
      vs 3.3%, P = .374) but lower rates of death/CHF/shock (5.2% vs 9.6%, P = .013).
      After multivariable adjustment, only post-PCI TMPG 2/3 was significantly
      associated with survival (P = .001), whereas residual ST-E (P = .606) and post
      PCI TIMI flow grade (P = .086) were not. Conversely, residual ST-E > or =2 mm (P
      = .012) rather than angiographic reperfusion was associated with the composite of
      death/CHF/shock events. CONCLUSION: Angiographic and electrocardiographic
      estimates of reperfusion with primary PCI in ST-segment elevation myocardial
      infarction provide different and complementary predictions of morbidity and
      mortality.

PMID- 19853694
TI  - Intake of total trans, trans-18:1, and trans-18:2 fatty acids and risk of sudden
      cardiac death in women.
AB  - BACKGROUND: Total intake of trans fat is associated with coronary heart disease
      (CHD), and recent reports in primarily male populations suggest that blood levels
      of specific trans isomers may have different effects on risk, particularly risk
      of sudden cardiac death (SCD). METHODS: We prospectively examined the association
      between dietary intake of trans fat and SCD among 86,762 women from the Nurses'
      Health Study. Coronary heart disease risk factors, including diet and lifestyle
      factors, were updated via questionnaires every 2 to 4 years, beginning in 1980.
      RESULTS: Over 26 years, we documented 317 SCD events. In the primary analysis, we
      found no significant association between intake of total trans fat, trans-18:1,
      or trans-18:2 isomers and risk of SCD. Compared to the lowest quintile of intake,
      the relative risk (95% CI) of SCD in the highest quintile was 1.28 (0.82-2.00)
      for total trans, 1.08 (0.64-1.83) for trans-18:1, and 1.19 (0.76-1.88) for trans
      18:2. In a secondary prespecified analysis, total trans fat was significantly
      related to SCD among women who reported a diagnosis of CHD before SCD (relative
      risk 3.24, 95% CI 1.42-7.40 for the highest vs lowest quintile, P trend = .01);
      however, the test for interaction was not significant (P = .11). CONCLUSIONS: In
      this large prospective cohort of women, neither dietary intake of trans fat nor
      the individual trans isomers, trans-18:1 and trans-18:2, were significantly
      associated with risk of SCD. However, trans fat intake may be associated with SCD
      risk among women with CHD, suggesting that trans fat intake may play a greater
      role in SCD risk among those with clinically manifest atherosclerosis.

PMID- 19853695
TI  - Addition of inspiratory muscle training to aerobic training improves
      cardiorespiratory responses to exercise in patients with heart failure and
      inspiratory muscle weakness.
AB  - BACKGROUND: This small clinical trial tested the hypothesis that the addition of
      inspiratory muscle training (IMT) to aerobic exercise training (AE) results in
      further improvement in cardiorespiratory responses to exercise than those
      obtained with AE in patients with chronic heart failure (CHF) and inspiratory
      muscle weakness (IMW). METHODS: Twenty-four patients with CHF and IMW (maximal
      inspiratory pressure <70% of predicted) were randomly assigned to a 12-week
      program of AE plus IMT (AE + IMT, n = 12) or to AE alone (AE, n = 12). Before and
      after intervention, the following measures were obtained: maximal inspiratory
      muscle pressure (PI(max)), peak oxygen uptake (Vo(2)peak), peak circulatory
      power, oxygen uptake efficiency slope, ventilatory efficiency, ventilatory
      oscillation, oxygen uptake kinetics during recovery (T(1/2)Vo(2)), 6-minute walk
      test distance, and quality of life scores. RESULTS: Compared to AE, AE + IMT
      resulted in additional significant improvement in PI(max) (110% vs 72%),
      Vo(2)peak (40% vs 21%), circulatory power, oxygen uptake efficiency slope,
      ventilatory efficiency, ventilatory oscillation, and T(1/2)Vo(2). Six-minute walk
      distance and quality of life scores improved similarly in the 2 groups.
      CONCLUSION: This randomized trial demonstrates that the addition of IMT to AE
      results in improvement in cardiorespiratory responses to exercise in selected
      patients with CHF and IMW. The clinical significance of these findings should be
      addressed by larger randomized trials.

PMID- 19853696
TI  - Cardiac resynchronization therapy in patients with ischemic versus non-ischemic
      heart failure: Differential effect of optimizing interventricular pacing
      interval.
AB  - BACKGROUND: Whether sequential biventricular pacing provides substantial benefits
      over conventional simultaneous stimulation remains unclear, particularly
      regarding the differences between ischemic and non-ischemic patients. The purpose
      of this study was to evaluate the acute effect of interventricular pacing
      interval (V-V) optimization on left ventricular (LV) systolic performance and
      dyssynchrony in ischemic versus non-ischemic patients. METHODS: Sixty-nine
      consecutive patients underwent cardiac resynchronization therapy. Within 3 days
      after implantation, V-V was optimized by measuring (every 20-millisecond
      interval) LV systolic performance (LV outflow-tract velocity-time-integral, LVOT
      VTI) and LV dyssynchrony (using tissue Doppler imaging). Optimal pacing
      configuration was the one achieving maximal increase in LVOT VTI. RESULTS:
      Optimized sequential pacing provided a significant improvement in LVOT VTI
      compared to simultaneous stimulation (from 138 +/- 42 to 163 +/- 38 mm, P < .001)
      and was associated with a significant reduction in LV dyssynchrony (from 33 +/-
      31 to 19 +/- 24 milliseconds, P < .001). The increase in LVOT VTI and LV ejection
      fraction after implantation was greater in non-ischemic as compared to ischemic
      patients (P < .001). However, V-V optimization yielded a larger improvement in LV
      systolic performance in ischemic patients (P = .03). Consequently, the 2 groups
      showed comparable response after V-V optimization. A significant correlation was
      observed between LV scar tissue and optimal V-V interval (r = 0.58, P < .001),
      with a larger extent of scar related to a larger level of LV preactivation,
      probably reflecting slow intra-LV conduction. CONCLUSIONS: Optimized sequential
      biventricular pacing further increased LV systolic performance as compared to
      simultaneous stimulation, particularly in ischemic patients where the presence of
      a large scar was correlated with a larger LV preactivation.

PMID- 19853697
TI  - Prognostic value of B-type natriuretic peptide for cardiovascular events
      independent of left ventricular end-diastolic pressure.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) correlates with left ventricular
      (LV) end-diastolic pressure (LVEDP) and predicts cardiovascular events. We sought
      to determine whether BNP has prognostic value independent of LVEDP. METHODS:
      Eligible patients were referred for coronary angiography between March 15, 2002,
      and April 30, 2008, at a single institution. Inclusion criteria were having BNP,
      LV ejection fraction (EF), and LVEDP measured within 24 hours of the angiogram.
      The predictive value of BNP for events independent of LVEDP, EF, and other
      confounders was determined. RESULTS: The study population (n = 1,059) was
      followed for a mean of 1.8 +/- 1.7 years. The mean age was 63 +/- 13 years. The
      median BNP value was 182 pg/mL; 59% of patients had LVEDP > or =16 mm Hg. B-type
      natriuretic peptide and LVEDP had a modest but statistically significant
      correlation (r = 0.24, P < .0001). After adjustment for LVEDP and EF, the hazard
      ratio for the composite outcome of heart failure admissions and death was 1.37
      (1.21-1.55, P < .0001) per unit increase in log BNP. After adjustment for BNP and
      EF, LVEDP did not predict heart failure admissions and death (hazard ratio 1.05
      [0.95-1.10], per 5-mm Hg increase, P = .30). Those with BNP value below the
      median had longer event-free survival as compared to those with BNP value above
      the median, regardless of the LVEDP strata (log-rank P < .0001 for LVEDP > or =16
      and <16 mm Hg). CONCLUSION: B-type natriuretic peptide has prognostic value
      independent of LVEDP in this cohort with suspected coronary artery disease,
      suggesting this biomarker is not just a prognostic surrogate for elevated LV
      filling pressure.

PMID- 19853698
TI  - The relation between platelet reactivity and glycemic control in diabetic
      patients with cardiovascular disease on maintenance aspirin and clopidogrel
      therapy.
AB  - BACKGROUND: High platelet reactivity (HPR) during aspirin and clopidogrel therapy
      in patients with diabetes has been reported and may affect outcomes. However, the
      relation of platelet reactivity to glycemic control is less studied in patients
      on dual antiplatelet therapy. METHODS: Platelet aggregation (PA) in response to 5
      and 20 micromol/L adenosine diphosphate (ADP) was compared in type 2 diabetic (n
      = 36) and nondiabetic patients (n = 35) undergoing elective stenting on aspirin
      and clopidogrel maintenance therapy. The relation of glycosylated hemoglobin
      (HbA(1c)) <7 g/dL (n = 16) and HbA(1c) > or =7 g/dL (n = 20) on PA was examined.
      High platelet reactivity was defined as >46% for 5 micromol/L ADP-induced and
      >59% for 20 micromol/L ADP-induced PA. RESULTS: Diabetic patients had higher 5
      and 20 micromol/L ADP-induced PA than nondiabetic patients (45 +/- 17 vs 33 +/-
      12, P = .009 and 52 +/- 19 vs 40 +/- 12, P = .004, respectively). Diabetic
      patients with HbA(1c) > or =7.0 g/dL had significantly higher 5 and 20 micromol/L
      ADP-induced PA versus patients with diabetes with HbA(1c) <7.0 g/dL (54 +/- 15 vs
      34 +/- 14, P < .001 and 62 +/- 14 vs 40 +/- 17, P < .001, respectively). Among
      diabetic patients with HbA(1c) > or =7 g/dL, the prevalence of HPR was 65% and
      60%; and among diabetic patients with HbA(1c) <7 g/dL, the prevalence of HPR was
      19% and 13% as measured by 5 and 20 micromol/L ADP-induced PA, respectively. A
      correlation was present between 5 and 20 micromol/L ADP-induced PA and HbA(1c) (r
      = 0.60 and 0.62, P = .0001, respectively). CONCLUSION: An important relation
      exists between glycemic control and platelet reactivity in patients with type 2
      diabetes mellitus treated with dual antiplatelet therapy. Poorly controlled
      patients with diabetes have the greatest platelet reactivity and may require
      alternative antiplatelet strategies, and further clinical investigations are
      warranted.

PMID- 19853699
TI  - Does intensity of rate control influence outcome in persistent atrial
      fibrillation? Data of the RACE study.
AB  - BACKGROUND: Large trials have demonstrated that rate control is an acceptable
      alternative for rhythm control. However, optimal heart rate during atrial
      fibrillation (AF) remains unknown. Aim of this analysis was to compare outcome
      between rate control > or =80 and <80 beat/min in patients with persistent atrial
      fibrillation. METHODS: In the RAte Control versus Electrical cardioversion for
      persistent atrial fibrillation study, 522 patients were included, and 256 were
      randomized to rate control. This post hoc analysis included patients randomized
      to rate control. Patients were divided according to their mean resting heart rate
      during follow-up, <80 beat/min (n = 75) or > or =80 beat/min (n = 139). The end
      point, a composite of cardiovascular mortality, heart failure, thromboembolic
      complications, bleeding, pacemaker implantation, and severe drug side effects,
      was compared between both groups. RESULTS: During follow-up (2.3 +/- 0.6 years),
      a significant difference between both groups in heart rate was observed (72 +/- 5
      vs 90 +/- 8 beat/min; P < .001). Rate control drugs were not significantly
      different between both groups. New York Heart Association class and fractional
      shortening remained unchanged in both groups. There were 17 (23%) end points in
      the low heart rate group and 24 (17%) in the higher heart rate group (absolute
      difference, 5.4 [-7.3 to 8.2]; P = ns). Independent predictors for the primary
      end point were coronary artery disease, digoxin use, and interrupted
      anticoagulation, not high heart rate. Quality of life was comparable in both
      groups during follow-up. CONCLUSIONS: In patients treated with a rate control
      strategy, no differences were observed in terms of cardiovascular morbidity,
      mortality, and quality of life between the observed differences in level of rate
      control throughout follow-up.

PMID- 19853700
TI  - Patterns of management of atrial fibrillation complicating coronary artery bypass
      grafting: Results from the PRoject of Ex-vivo Vein graft ENgineering via
      Transfection IV (PREVENT-IV) Trial.
AB  - BACKGROUND: Current practice related to the management of atrial fibrillation
      (AF) complicating coronary artery bypass grafting (CABG) is uncertain. METHODS:
      We examined management of post-CABG AF in the PREVENT-IV trial, and we explored
      patterns of use of postoperative rhythm versus rate control and anticoagulation
      for AF by geographic region and type of site. We also compared outcomes of
      patients who developed post-CABG AF (663) with those who did not (2,131).
      RESULTS: The incidence of AF was 24%. Post-CABG AF was treated with a rhythm
      control strategy in 81% of patients and with warfarin in 23% of patients.
      Although there were significant variations across sites in the management of post
      CABG AF, patterns of use of postoperative rhythm versus rate control and
      anticoagulation did not differ by geographic region or by whether or not the
      enrolling site was an academic institution. Mortality was higher in patients with
      post-CABG AF than patients without AF at 30 days (1.5% vs 0.7%, P = .01) but not
      at 3 years (6.9% vs 4.9%, P = .41). There was a trend toward a higher risk of
      mortality or stroke at 30 days in patients with AF (2.4% vs 1.9%, P = .08).
      CONCLUSION: Although a rhythm control strategy was used in most of the patients
      in this trial and the overall rate of use of warfarin was low, the significance
      of these findings is uncertain because of the lack of data from randomized
      clinical trials. The substantial variations in the management of post-CABG AF
      across sites are likely because of definitive data on the most effective
      therapies, highlighting the need for clinical trials on rate versus rhythm
      control and on anticoagulation for AF in this setting.

PMID- 19853702
TI  - Prognostic significance and magnetic resonance imaging findings in aborted
      myocardial infarction after primary angioplasty.
AB  - BACKGROUND: Aborted myocardial infarction (MI) is defined by major (> or =50%) ST
      segment resolution and a lack of subsequent cardiac enzyme rise > or =2 the upper
      normal limit. This ultimate myocardial salvage has been observed in approximately
      15% of ST-elevation MI (STEMI) patients after fibrinolysis. So far, the
      prognostic significance and magnetic resonance imaging (MRI) findings of an
      aborted MI after primary angioplasty have not been evaluated appropriately.
      METHODS: We examined 420 consecutive STEMI patients undergoing primary
      angioplasty within 12 hours after symptom onset. All patients underwent MRI
      within 1 to 4 days. Clinical end points were major adverse cardiovascular events
      within 6 months after the index event. RESULTS: Of the 420 STEMI patients, 58
      (14%) fulfilled aborted MI criteria. As compared with true MI, patients with
      aborted MI had a significant lower infarct size, shorter pain-to-balloon time,
      and better left ventricular ejection fraction (P < .001, respectively). Aborted
      MI patients had a 6-month major adverse cardiovascular event rate of 1.7% versus
      19.6% of true MI patients (P = .001). In aborted MI patients, MRI detected no
      myocardial scar in 30 (56%), and a minor necrosis/scar formation in 24 patients
      (44%). CONCLUSION: The proven prognostic relevance of aborted MI makes it a
      meaningful end point and therapeutic target in future MI studies. MRI can further
      distinguish between true aborted MI with absence of myocardial scar and aborted
      MI with scar formations.

PMID- 19853701
TI  - Histologic characterization of hypertrophic cardiomyopathy with and without
      myofilament mutations.
AB  - BACKGROUND: Between 30% and 60% of clinical cases of hypertrophic cardiomyopathy
      (HC) can be attributed to mutations in the genes encoding cardiac myofilament
      proteins. Interestingly, it appears that the likelihood of an underlying
      myofilament mutation can be predicted by echocardiographic assessment of left
      ventricular morphology. However, it is not known whether genotypically
      characterized HC exists as a separate entity with discrete phenotypic morphology
      and histology or to what extent recognized polymorphisms of the renin-angiotensin
      aldosterone system (RAAS) influence this relationship. The presence of cardiac
      myofilament and mutations and RAAS polymorphisms will have a strong association
      with the severity of histologic features of HC and characteristic septal shape.
      METHODS: We conducted a retrospective review of histology specimens, obtained at
      septal myectomy among 181 patients with medically refractory symptomatic HC. All
      patients underwent comprehensive genetic analysis for mutations in 8 myofilament
      encoding genes; a subset was genotyped for 6 known RAAS-polymorphisms. Patients
      underwent comprehensive echocardiography by an expert blinded to genotype and
      microscopic status. RESULTS: Microscopically, severity of myocyte hypertrophy
      appears to be associated with the presence of recognized HC cardiac myofilament
      mutations (P = .03). Other histologic features characteristic of HC were not
      consistently associated with myofilament mutation status. A higher burden of pro
      LVH RAAS polymorphisms also appeared to predict only myocyte hypertrophy (P =
      .01). The presence of RAAS polymorphisms was not associated with the development
      of a specific septal morphology (P = .6). CONCLUSION: Myofilament-positive HC
      does not appear to represent a distinct clinical phenotypic entity as evidenced
      by specific histologic characteristics and septal shape.

PMID- 19853703
TI  - Transradial versus transfemoral percutaneous coronary intervention in acute
      myocardial infarction Systematic overview and meta-analysis.
AB  - BACKGROUND: Although transradial percutaneous coronary intervention (TRPCI) is
      widely applied for percutaneous procedures, its safety in the setting of ST
      segment elevation (STEMI) is controversial. Our aim was to assess the safety and
      efficacy of TRPCI versus transfemoral PCI in the context of treating patients
      suffering acute myocardial infarction with STEMI. METHODS: Randomized, case
      control, and cohort studies comparing access-related complications were analyzed.
      Our objective was to determine if radial access reduces major bleeding and
      thereby reduces death and ischemic events compared to femoral access in this
      setting. A fixed-effects model was used with random effects for sensitivity
      analysis. RESULTS: Twelve studies involving 3324 patients were identified.
      Transradial PCI reduced major bleeding compared to transfemoral PCI (P = .0001),
      and significant reductions were found in the composite of death, myocardial
      infarction, or stroke (P = .001). Mortality reduction showed a significant toward
      benefit in the case of TRPCI (2.04% vs 3.06%, OR 0.54 [95% CI 0.33-0.86], P =
      .01). The fluoroscopic time was longer, and access site crossover was more
      frequent for TRPCI (P = .001, P < .00001, respectively). CONCLUSIONS: Transradial
      PCI reduces the risk of periprocedural major bleeding and major adverse events in
      the STEMI setting.

PMID- 19853705
TI  - Achieving routine sub 30 minute door-to-balloon times in a high volume 24/7
      primary angioplasty center with autonomous ambulance diagnosis and immediate
      catheter laboratory access.
AB  - BACKGROUND: In primary angioplasty (primary percutaneous coronary intervention
      [PPCI]) for acute myocardial infarction, institutional logistical delays can
      increase door-to-balloon times, resulting in increased mortality. METHODS: We
      moved from a thrombolysis (TL) service to 24/7 PPCI for direct access and
      interhospital transfer in April 2004. Using autonomous ambulance diagnosis with
      open access to the myocardial infarction center catheter laboratory, we compared
      reperfusion times and clinical outcomes for the final 2 years of TL with the
      first 3 years of PPCI. RESULTS: Comparison was made between TL (2002-2004, n =
      185) and PPCI (2004-2007, n = 704); all times are medians in minutes
      (interquartile range): for TL, symptom to needle 153 (85-225), call to needle 58
      (49-73), first professional contact (FPC) to needle 47 (39-63), door to needle 18
      (12-30) (mortality: 7.6% at 30 days, 9.2% at 1 year); for interhospital transfer
      PPCI (n = 227), symptom to balloon 226 (175-350), call to balloon 135 (117-188),
      FPC to balloon 121 (102-166), first door-to-balloon 100 (80-142) (mortality: 7.0%
      at 30 days, 12.3% at 1 year); for direct-access PPCI (n = 477), symptom to
      balloon 142 (101-238), call to balloon 79 (70-93), FPC to balloon 69 (59-82),
      door to balloon 20 (16-29) (mortality: 4.6% at 30 days, 8.6% at 1 year). There
      was no difference between direct-access PPCI and TL times for symptom to
      needle/balloon. Direct-access PPCI was significantly quicker for the group than
      in-hospital thrombolysis for door to needle/balloon times due to the lack of any
      long wait patients (P < .001). CONCLUSIONS: Interhospital transfer remains slow
      even with rapid institutional door-to-balloon times. With autonomous ambulance
      diagnosis and open access direct to the catheter laboratory, a median door-to
      balloon time of <30 minutes day and night was achieved, and >95% of patients were
      reperfused within 1 hour.

PMID- 19853706
TI  - Incremental value of 2-dimensional speckle tracking strain imaging to wall motion
      analysis for detection of coronary artery disease in patients undergoing
      dobutamine stress echocardiography.
AB  - BACKGROUND: Interpretation of dobutamine stress echocardiogram (DSE) is often
      subjective and requires expert training. The purposes of this study was to
      determine optimal cutoff values for longitudinal, circumferential, and radial
      strains at peak DSE for detection of significant stenoses on coronary angiography
      and to investigate incremental value of combining strain measurements to wall
      motion analysis. METHODS: In this multicenter study, 102 patients underwent
      concomitant DSE and coronary angiography. Optimal cutoff values for mean global
      longitudinal (-20%), global circumferential (-26%), and mean radial (50%) strains
      at peak stress for detection of significant stenoses on coronary angiography were
      determined in a derivation group (n = 62) and tested in a prospectively recruited
      validation group (n = 40). RESULTS: Respective sensitivities for longitudinal,
      circumferential, radial strains, and expert wall motion score index (WMSI) were
      84.2%, 73.9%, 78.3%, and 76%; respective specificities were 87.5%, 78.6%, 57.1%,
      and 92.9%; and respective accuracies were 85.2%, 75.7%, 70.3%, and 82.1%.
      Longitudinal strain analysis had comparable accuracy to WMSI (P = .70). However,
      combination longitudinal strain and WMSI had the highest sensitivity,
      specificity, and accuracy (100%, 87.5%, and 96.3% respectively), and its
      diagnostic accuracy was incremental to either longitudinal strain (P = .034) or
      WMSI alone (P = .008). CONCLUSION: Longitudinal strain analysis had higher
      diagnostic accuracy than circumferential and radial strains and was comparable to
      WMSI for detection of significant coronary artery disease. However, combination
      longitudinal strain and WMSI resulted in significant incremental increase in
      diagnostic accuracy.

PMID- 19853704
TI  - Nephrotoxicity of iodixanol versus iopamidol in patients with chronic kidney
      disease and diabetes mellitus undergoing coronary angiographic procedures.
AB  - BACKGROUND: The choice of radiographic contrast media for use in patients at
      increased risk of contrast-induced nephropathy (CIN) is of ongoing interest.
      METHODS: The current study is a prospective, multicenter, randomized, double
      blind design comparing the renal effects of the non-ionic, iso-osmolal agent,
      iodixanol, versus the non-ionic, low-osmolal agent, iopamidol, in 526 subjects
      with impaired baseline renal function (chronic kidney disease) and diabetes
      mellitus undergoing diagnostic and/or therapeutic coronary angiographic
      procedures. The co-primary end points were the peak increase in serum creatinine
      (SCr) and the incidence of CIN (increase > or =0.5 mg/dL) in SCr from baseline
      within 3 days of receiving contrast media. RESULTS: In 418 evaluable subjects
      with complete postcontrast media SCr data, the median peak increase in SCr in the
      iodixanol arm was 0.10 mg/dL, whereas in the iopamidol arm, the median peak
      increase was 0.09 mg/dL (P = .13). The overall CIN incidence was 10.5% (11.2% %
      in the iodixanol arm and 9.8% in the iopamidol arm, P = .7). The volume of
      contrast media, volume of saline administered, frequency of coronary
      interventional procedures, and severity of baseline kidney disease and of
      diabetes mellitus were similar between treatments. CONCLUSIONS: In the present
      study, the overall rate of CIN in patients with chronic kidney disease and DM
      undergoing coronary angiographic procedures was 10.5%. There was no significant
      difference between iodixanol and iopamidol in either peak increase in SCr or risk
      of CIN.

PMID- 19853707
TI  - Additional prognostic value of physical examination, exercise testing, and
      arterial ultrasonography for coronary risk assessment in primary prevention.
AB  - BACKGROUND: The choice of noninvasive tests used in primary prevention of
      cardiovascular diseases must be based on medical evidence. The aim of this study
      was to assess the additional prognostic value, over conventional risk factors, of
      physical examination, exercise testing, and arterial ultrasonography, in
      predicting a first coronary event. METHODS: A prospective cohort study was
      conducted between 1996 and 2004 (n = 2,709), with follow-up in 2006 (response
      rate 96.6%). Participants had no history or symptoms of cardiovascular disease
      and had a standardized physical examination, a cardiac exercise testing, and
      carotid and femoral ultrasonography at baseline. Incident cases of definite
      coronary events were recorded during follow-up. RESULTS: Over the Framingham risk
      score, femoral bruit, positive exercise test, intima-media thickness >0.63 mm,
      and a femoral plaque provided significant additional information to the
      prediction model. The addition of the exercise test to the traditional risk
      factors, then the intima-media thickness and lastly the presence of femoral
      plaques, produces incremental increases in the area under the receiver operating
      characteristic curve (0.73-0.78, P = .02) and about a 50% increase in the
      positive predictive value (15.8%-31.4%), with no effect on the negative
      predictive value (96.4%-96.9%). CONCLUSION: Physical examination, exercise
      testing, and arterial ultrasonography provide incremental information on the risk
      of coronary event in asymptomatic adults. Exercise testing and femoral
      ultrasonography also improve the accuracy of the risk stratification.

PMID- 19853708
TI  - Barriers to participation in cardiac rehabilitation.
AB  - BACKGROUND: Participation rates in cardiac rehabilitation after myocardial
      infarction (MI) remain low. Studies investigating the predictive value of
      psychosocial variables are sparse and often qualitative. We aimed to examine the
      demographic, clinical, and psychosocial predictors of participation in cardiac
      rehabilitation after MI in the community. METHODS: Olmsted County, Minnesota,
      residents hospitalized with MI between June 2004 and May 2006 were prospectively
      recruited, and a 46-item questionnaire was administered before hospital
      dismissal. Associations between variables and cardiac rehabilitation
      participation were examined using logistic regression. RESULTS: Among 179 survey
      respondents (mean age 64.8 years, 65.9% male), 115 (64.2%) attended cardiac
      rehabilitation. The median (25th-75th percentile) number of sessions attended
      within 90 days of MI was 13 (5-20). Clinical characteristics associated with
      rehabilitation participation included younger age (odds ratio [OR] 0.95 per 1
      year increase), male sex (OR 1.93), lack of diabetes (OR 2.50), ST-elevation MI
      (OR 2.63), receipt of reperfusion therapy (OR 7.96), in-hospital cardiologist
      provider (OR 18.82), no prior MI (OR 4.17), no prior cardiac rehabilitation
      attendance (OR 3.85), and referral to rehabilitation in the hospital (OR 12.16).
      Psychosocial predictors of participation included placing a high importance on
      rehabilitation (OR 2.35), feeling that rehabilitation was necessary (OR 10.11),
      better perceived health before MI (excellent vs poor OR 7.33), the ability to
      drive (OR 6.25), and post-secondary education (OR 3.32). CONCLUSIONS: Several
      clinical and psychosocial factors are associated with decreased participation in
      cardiac rehabilitation programs after MI in the community. As many are
      modifiable, addressing them may improve participation and outcomes.

PMID- 19853709
TI  - Low- and high-density lipoprotein cholesterol goal attainment in dyslipidemic
      women: The Lipid Treatment Assessment Project (L-TAP) 2.
AB  - BACKGROUND: Differences between women and men have been documented for both
      diagnostic testing and treatment in cardiology. This analysis evaluates whether
      low-density lipoprotein cholesterol (LDL-C) success rates according to current
      guidelines and high-density lipoprotein cholesterol (HDL-C) levels differ by
      gender in the L-TAP 2 population. METHODS: Patients aged > or =20 years with
      dyslipidemia on stable lipid-lowering therapy were assessed in 9 countries
      between September 2006 and April 2007. Low-density lipoprotein cholesterol goal
      attainment by cardiovascular risk level and region and determinants of low HDL-C
      were compared between genders. RESULTS: Of 9,955 patients (45.3% women)
      evaluated, women had a significantly lower overall LDL-C success rate than men
      (71.5% vs 73.7%, P = .014), due entirely to the difference in the high
      risk/coronary heart disease (CHD) group (LDL-C goal <100 mg/dL, 62.6% vs 70.6%, P
      < .0001) Among CHD patients with > or =2 additional risk factors, only 26.7% of
      women and 31.5% of men (P = .021) attained the optional LDL-C goal of <70 mg/dL.
      High-density lipoprotein cholesterol was <50 mg/dL in 32.2% of women and <40
      mg/dL in 26.8% of men (P < .0001), including 38.2% of women and 29.8% of men in
      the high risk/CHD group (P < .0001). Predictors of low HDL-C in women included
      diabetes, smoking, waist circumference, and hypertension. CONCLUSIONS:
      Cholesterol treatment has improved substantially since the original L-TAP a
      decade ago, when only 39% of women attained their LDL-C goal. However, high-risk
      women are undertreated compared to men, and a substantial opportunity remains to
      reduce their cardiovascular risk.

PMID- 19853711
TI  - Mortality associated with adult congenital heart disease: Trends in the US
      population from 1979 to 2005.
AB  - BACKGROUND: Significant advances over the last 5 decades have allowed most
      patients with congenital heart disease to survive well past childhood and into
      adulthood. Population-based data from the United States are limited regarding
      mortality in adult survivors. METHODS: We used the Center for Disease Control
      Multiple Cause-of-Death registry to determine trends in mortality from 1979 to
      2005 among individuals with congenital heart disease in the United States.
      RESULTS: There were significant reductions in death rates for adults with a
      number of congenital defects including ventricular septal defect, patent ductus
      arteriosus, coarctation of the aorta, and Ebstein anomaly. Notably, when all ages
      were analyzed, there was a 71% decline in deaths associated with transposition of
      the great arteries (P = .001) and a 40% reduction in deaths associated with
      tetralogy of Fallot (P < .001). Mortality related to other lesions declined as
      well. Among adults with cyanotic lesions, the primary contributing cause of death
      was arrhythmia followed by heart failure. For adults with noncyanotic lesions,
      the major contributing cause before 1990 was arrhythmia; after 1990, myocardial
      infarction became the leading contributing cause of death. There was an overall
      decrease in the incidence of arrhythmia as the cause of death in all ages,
      particularly among children. CONCLUSIONS: Patients with congenital heart disease
      are living longer. Arrhythmia remains the primary contributing cause of death for
      those with cyanotic lesions. Myocardial infarction is now the leading
      contributing cause for adults with noncyanotic congenital heart disease
      consistent with late survival and an increasing impact of acquired heart disease.

PMID- 19853710
TI  - Self-reported anxiety and the risk of clinical events and atherosclerotic
      progression among patients with Coronary Artery Bypass Grafts (CABG).
AB  - BACKGROUND: Symptoms of anxiety are associated with increased risk of coronary
      artery disease and potentially poor prognosis among patients with existing
      coronary artery disease, but whether symptoms of anxiety influence
      atherosclerotic progression among such patients is uncertain. Accordingly, we
      evaluated the hypotheses that symptoms of anxiety are associated with adverse
      clinical outcomes and progression of atherosclerosis among individuals with
      previous coronary artery bypass graft (CABG) surgery and saphenous vein grafts
      enrolled in the Post-CABG Trial. METHODS: The Post-CABG Trial randomized patients
      with a history of CABG surgery to either aggressive or moderate lipid lowering
      and to either warfarin or placebo. Patients were followed up for clinical end
      points and coronary angiography was conducted at enrollment and after a median
      follow-up of 4.3 years. Anxiety symptoms were assessed at enrollment using the
      state portion of the Spielberger State-Trait Anxiety Inventory (STAI) in 1317
      patients. RESULTS: In models adjusting for age, sex, race, treatment assignment
      and years since CABG surgery, a STAI score > or =40 was positively associated
      with risk of death or myocardial infarction (MI) (OR 1.55, 95% CI 1.01-2.36, P =
      .044). This association was attenuated slightly when depressive symptoms were
      included in the model, but lost statistical significance (P = .11). There was a
      dose-response relationship between STAI score and risk of death or MI. There was
      no association between self-reported anxiety and atherosclerotic progression of
      grafts. CONCLUSIONS: Anxiety symptoms are associated with increased risk of death
      or MI among patients with saphenous vein grafts, but this risk does not appear to
      be mediated by more extensive atherosclerotic progression.

PMID- 19853712
TI  - [Specific trait and state anxiety's roles in emergence and maintenance of
      attentional biases associated with anxiety: Inventories and investigation
      tracks].
AB  - BACKGROUND: During these two last decades, much research has shown that anxiety
      can be characterised by an attentional bias favouring threat stimuli processing.
      This bias plays a central role in the development and maintenance of pathological
      states associated with anxiety. The first part of this article concerns numerous
      variables that elucidate parts of the appearance and maintenance conditions of
      attentional bias associated with anxiety. Thus, clinical versus non-clinical
      states of individuals play an important role in attentional behaviour of anxiety:
      at an early stage of information processing, which involves mainly automatic
      processes, the attentional bias appears whatever the status of anxious
      individuals. At a later stage, which involves controlled processes, non-clinical
      anxious subjects would be able to use defensive strategies, which allow them to
      counterbalance the bias that appeared before, while clinical anxious subjects
      would not be able to ignore this threat, because of the major rooting of their
      anxiety. A vigilance attentional bias would be shown in clinical individuals
      throughout a continuum of information processing. In addition, a near unanimous
      observation highlights the importance of the material specificity in obtaining
      attentional bias. However, this observation appears less obvious for the
      subliminal condition in which anxious individuals can perfect a surface analysis
      of the material, identifying the emotional valence of a word and not its
      specificity. Literature findings on anxiety impact in order to release more
      clarity and in an attempt to explain empirical results that sometimes remain
      contradictory; the second part of this article is particularly focused on another
      research track, rarely used but very promising: it concerns differentiating the
      specific roles of anxiety state and anxiety trait in the attentional patterns.
      The anxiety trait is defined as "an acquired behavioural disposition, which
      predisposes an individual to perceive a whole of circumstances objectively and
      not as dangerous or threatening". On the other hand, anxiety state reflects
      variable component and is defined as an emotive state "characterized by
      subjective and conscious feelings of apprehension and tension associated with an
      activation of the autonomous nervous system". For a long time, researchers have
      mainly focused on this first variable while occulting the second. However,
      various theoretical models underline that the anxiety trait variable alone is
      certainly a condition necessary but insufficient in the appearance and
      maintenance of attentional bias. Thus, some empirical research, highlighting the
      potential role of the anxiety state was born. Although they have, for the moment,
      a limited range due to the heterogeneity of their results, these studies open a
      new route of considerable research. Thus, on the preattentive level, the dominant
      role of the interaction between anxiety state and anxiety trait in the release of
      bias was highlighted in a near consensual way. It is not the same at a later
      stage of information processing, which is a stage where two tracks of results are
      confronted: a part of research suggests that maintenance of bias is due to, as at
      the preattentive level, an interactive effect of state and trait anxieties,
      whereas other research shows a central role of anxiety state in maintenance of
      attentional bias. Recent studies using different paradigms confirm the idea of a
      central role of anxiety state. Further research, separating the specific roles of
      state and trait anxiety, will be necessary to decide clearly. DISCUSSION: Various
      explanatory tracks were suggested to try to clear up these data. Thus, it's
      possible that the time-course of the stressor may be an important variable. In
      addition, the review highlights that state anxiety averages are too often far
      from the norms established by Spielberger et al. In short, if the state anxiety
      level is not sufficiently high in a number of searches, it then appears difficult
      to highlight the attentional biases, which are associated with it. Among them,
      the resort to a methodology combining physiological measurements (salivary index,
      ocular movements recording...) and cognitive measurements (questionnaires, dot
      probe paradigm, Stroop task...) seems to warrant a better understanding of
      attentional processes.

PMID- 19853713
TI  - [Self-esteem, self-centeredness and social-emotional adjustment of gifted
      children and adolescents].
AB  - BACKGROUND: There is an ongoing debate of how giftedness affects social-emotional
      adjustment. Self-esteem may be an indicator of social-emotional adjustment but
      insufficient in its explanatory capacity, especially high self-esteem which tends
      to produce opposite responses in regards to adjustment. A distinction between
      defensive and genuine high self-esteem could account for these results. In order
      to understand how self-esteem operates on social-emotional adjustment, it should
      be associated with other measurements relating to self-concern. In the Rorschach
      comprehensive system (CS), egocentricity index measures self-centeredness, which
      can be defined as the balance between self-concern and concern for others. High
      self-concern is associated with a neglect of the others. Operationalized here, as
      the interaction of high self-esteem and excessive self-concern, defensive high
      self-esteem should predict maladaptive outcomes. METHOD: Participants were aged
      from 9 to 15 years old, with an IQ greater or equal to 130 on the WISC-III. They
      were attending regular classes and were not in counseling or psychotherapy.
      Children and adolescents were administrated the Rorschach CS and the Coopersmith
      self-esteem inventory. Parents completed the child behaviour checklist (CBCL)
      which assesses general psychopathology. RESULTS: Seventy-eight subjects' data
      satisfy the conditions of validity of the instruments used. Gifted boys present
      more behavior and emotional problems than gifted girls in this study. Self-esteem
      predicts social-emotional adjustment. There is an interaction between self-esteem
      and self-concern on psychopathology only for high values of self-esteem. Gifted
      with high self-esteem associated with high self-concern are more vulnerable to
      maladjustment than high self-esteem associated with low self-concern. Gifted
      children and adolescents with low self-esteem experience more problems anyhow.
      CONCLUSION: These findings reinforce the view that the gifted are a diverse group
      in terms of social-emotional adjustment and self-esteem. Self-esteem operates as
      a valuable resource for the social-emotional adjustment of gifted children and
      adolescents but only under some conditions. Low self-esteem gifted seem to be at
      more risk of maladjustment, but that does not mean any causal relationship.
      Gifted children and adolescents with high self-esteem can be considered as a
      heterogeneous category. High self-esteem associated to excessive self-concern has
      less beneficial effects on adjustment than high self-esteem associated to low
      self-concern.

PMID- 19853714
TI  - [Heart rate variability. Applications in psychiatry].
AB  - BACKGROUND: The autonomic nervous system sends messages through the sympathetic
      and parasympathetic nervous system. The sympathetic nervous system innervates the
      cardioaccelerating center of the heart, the lungs (increased ventilatory rhythm
      and dilatation of the bronchi) and the non-striated muscles (artery contraction).
      It releases adrenaline and noradrenaline. As opposed to the sympathetic nervous
      system, it innervates the cardiomoderator center of the heart, the lungs (slower
      ventilatory rhythm and contraction of the bronchi) and the non-striated muscles
      (artery dilatation). It uses acetylcholine (ACh) as its neurotransmitter.
      Sympathetic and parasympathetic divisions function antagonistically to preserve a
      dynamic modulation of vital functions. These systems act on the heart
      respectively through the stellar ganglion and the vagus nerve. The interaction of
      these messages towards the sinoauricular node is responsible for normal cardiac
      variability, which can be measured by monitoring heart rate variability (HRV).
      Heart rate is primarily controlled by vagal activity. Sensorial data coming from
      the heart are fed back to the central nervous system. HRV is an indicator of both
      how the central nervous system regulates the autonomic nervous system, and of how
      peripheral neurons feed information back to the central level. HRV measures are
      derived by estimating the variation among a set of temporally ordered interbeat
      intervals. The state of perfect symmetry, which, in medical parlance, is called
      respiratory sinus arrhythmia (RSA), can be described as a state of cardiac
      coherence. Obtaining a series of interbeat intervals requires a continuous
      measure of heart rate, typically electrocardiography (ECG). Commercially
      available software is then used to define the interbeat intervals within an ECG
      recording. LITERATURE FINDINGS: The autonomic nervous system is highly adaptable
      and allows the organism to maintain its balance when experiencing strain or
      stress. Conversely, a lack of flexibility and a rigid system can lead to somatic
      and psychological pathologies. Several studies have shown a link between reduced
      HRV in postmyocardial infarction patients and increased risk for adverse
      cardiovascular events, including ventricular arrhythmias and sudden death.
      Recently, studies indicate that patients with depression and anxiety disorders
      exhibit abnormally low HRV compared with non-psychiatric controls. Reduced HRV
      seems indicate decreased cardiac vagal tone and elevated sympathetic activity in
      anxious and depressive patients and would reflect deficit in flexibility of
      emotional physiological mechanisms. A few studies have also revealed that
      biofeedback using respiratory control, relaxation and meditation techniques can
      increase HRV. For now, there is insufficient data to determine if paced
      respiration or subjective relaxation is necessary or sufficient for the efficacy
      of HRV biofeedback. Although the literature is modest, this review suggests that
      the use of biofeedback with relaxation and meditation approaches may result in
      increased HRV and parasympathetic activity. Limitations of the review literature
      have also been considered to identify areas for future research.

PMID- 19853715
TI  - [Renal transplantation, anxiety and depressive disorders and quality of life].
AB  - Until now there are few data in the literature describing psychiatric comorbidity
      in patients waiting for renal transplantation. We have conducted a cross
      sectional study estimating the prevalence of anxiety and depressive disorders in
      three groups of renal transplant patients, before transplantation, six months and
      one year after. The MINI was used to estimate the prevalence of anxiety and
      depressive disorders. Anxiety and depressive symptoms were assessed using the
      HAD. Patients' quality of life was also assessed using the SF-36. This study did
      not find any major impact of renal transplantation on the prevalence of
      structured psychiatric disorders. Indeed, the prevalence of depressive and
      anxiety disorders did not differ significantly between the three groups. The mean
      scores of anxiety did not differ significantly between the three groups in
      contrast to the mean scores of depression, which differed significantly between
      the group "before transplantation" and the group "one year after
      transplantation". We did not find any significant difference concerning the
      scores of patient's quality of life between the three groups, except for the item
      "health perceived by the patients themselves". Health perceived by the patients
      was greater in the group "after transplantation". The quality of life of dialysed
      or transplant patients was strongly correlated with anxiety and depressive
      symptoms scores, emphasizing the major interest of a multidisciplinary approach
      for these patients.

PMID- 19853716
TI  - [Psychometric properties of the Questionnaire de Fonctionnement Social in
      borderline personality disorder].
AB  - OBJECTIVE: Social functioning is a primordial aspect of mental health and it
      should be considered as an important outcome measure in psychiatric treatments
      and studies. Few short and simple assessment instruments are available in French.
      Recently, the Questionnaire de Fonctionnement Social (QFS) was developed to study
      social behavior of psychiatric patients. The QFS is a 16-item self-report
      questionnaire assessing the frequency of and the satisfaction with social
      behavior during the last two weeks. The aim of the present study is to explore
      QFS psychometric properties in a sample of patients with borderline personality
      disorder. METHODS: Eighty-six outpatients (78 women and eight men, mean age:
      30.5+/-8.6) with borderline personality disorder and 100 healthy matched control
      subjects (89 women and 11 men, mean age: 30.2+/-7.7) completed the QFS. The
      convergent and divergent validities of the QFS were tested with the following
      instruments: Social Adaptation Self-Evaluation Scale (SASS), Brief Symptom
      Inventory (BSI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS)
      and a visual scale of suffering (EVS). Test-retest reliability of the QFS was
      calculated in a sub-sample of 28 subjects and its sensitivity to change was
      measured for 45 patients. RESULTS: Internal consistency of the QFS' global index
      was satisfying (Cronbach alpha from 0.59 to 0.84). Test-retest reliability of the
      QFS indexes ranged from 0.77 to 0.79 (intraclass correlation coefficient).
      Correlations between QFS and SASS demonstrated moderate convergent validity
      (r>0.59) whilst associations with others psychological measures (BSI, BDI, BHS,
      EVS) showed satisfying divergent validity (-0.42<r<-0.12). Discriminate validity
      was excellent as the group of healthy control subjects scored significantly
      higher than the group of patients in all variables (Mann-Whitney all p<0.001).
      QFS sensitivity to change after psychotherapeutic treatment was good as shown by
      the significant change observed in Frequency and Satisfaction index (Wilcoxon
      respectively p=0.002 and p<0.001). CONCLUSION: The QFS demonstrated satisfying
      psychometric properties in the studied population. This study confirms it is a
      valuable tool to assess social functioning of borderline personality disorder
      patients.

PMID- 19853717
TI  - [Relationship between depressive symptoms, hopelessness and suicidal ideation
      among 1547 high school students].
AB  - OBJECTIVES: The aim of the study was to evaluate the incidence of depressive
      symptoms and suicidal ideation, and to test the mediating role of hopelessness
      between depressive symptoms and the wish to kill oneself. METHOD: A random sample
      of 1547 high school students from the department of Haute-Garonne, France, (854
      girls, mean age=16.9+/-1.5; 693 boys, mean age=17.4+/-1.5) completed a
      questionnaire assessing cannabis use, the Center for Epidemiological Studies
      Depression Scale (CES-D) completed by the three items subscale measuring suicidal
      ideation proposed by Garrison et al. (1991) ("I felt life was not worth living";
      "I felt like hurting myself"; "I felt like killing myself"). The measure of
      hopelessness was based on a single item, "I felt life was not worth living".
      RESULTS: At least occasional wish to kill oneself were reported by 13% of boys
      and 14% of girls (NS). The mean CES-D score for girls was significantly higher
      than for boys (20.3+/-10.7 versus 16.7+/-9.9; p<0.01). According to the cut-off
      score of 24, 19% of boys and 34% of girls had a moderate to severe depressive
      symptomatology (p<0.0001). The mean suicidal ideation score was significantly
      higher in participants scoring 24 or above on the CES-D than participants scoring
      less than 24 (2.4+/-2.7 versus 0.3+/-0.9; p<0.0001). Among participants with CES
      D greater or equal to 24, 34% reported at least occasional wish to kill oneself
      versus 6% of participants with CES-D less than 24 (p<0.0001). CES-D scores and
      suicidal ideation scores were moderately correlated in girls (Pearson's r=0.59)
      and boys (r=0.61) in the total sample. To explore the role of hopelessness as
      mediator between depressive symptoms and the wish to kill oneself, multiple
      regression analyses were performed separately by gender. To establish mediation,
      three regression equations should be estimated and the four following conditions
      must hold: First, the independent variable (CES-D scores) must affect the
      mediator in the first equation; second, the independent variable must affect the
      dependent variable (the wish to kill oneself) in the second equation; third, the
      mediator must affect the dependent variable in the third equation regressing the
      dependent variable on both the independent variable and on the mediator; fourth,
      the effect of the independent variable on the dependent variable must be less in
      the third equation than in the second. Among girls, in the first equation, CES-D
      score explained 35% of the variance of hopelessness (beta=0.59, t=21.5, p<0.001).
      In the second equation, CES-D score explained 16% of the variance in the wish to
      kill oneself (beta=0.40, t=12.7, p<0.001). In the third equation, CES-D and
      hopelessness scores explained 32% of the variance in the wish to kill oneself.
      Hopelessness was the main predictor (beta=0.50, t=14, p<0.001) while the effect
      of CES-D was markedly reduced (beta=0.10, t=2.9, p<0.01). Among boys, in the
      first equation, CES-D score explained 38% of the variance of hopelessness
      (beta=0.62, t=20.7, p<0.001). In the second equation, CES-D score explained 25%
      of the variance in the wish to kill oneself (beta=0.50, t=15.1, p<0.001). In the
      third equation, CES-D and hopelessness scores explained 47% of the variance in
      the wish to kill oneself. Hopelessness was the main predictor (beta=0.60, t=17,
      p<0.001) while the effect of CES-D was substantially weakened (beta=0.13, t=3.6,
      p<0.001). DISCUSSION: These results showed a strong association between
      depressive symptoms and suicidal ideation in this nonclinical sample of
      adolescents. According to Beck's assumption, hopelessness appeared to be a
      mediator between depressive symptoms and the wish to kill oneself both in boys
      and girls. These findings are relevant for prevention and therapy. They suggest
      that targeting hopelessness may be as important in adolescents as in adults to
      reduce suicidal ideation and prevent suicidal attempts.

PMID- 19853718
TI  - [Impact of personality disorders in a sample of 212 homeless drug users].
AB  - INTRODUCTION: The impact of the mental disorders (axis I and II, according to DSM
      IV) on psychosocial problems (axis IV) is now a well-known fact, notably when
      substance abuse disorders are encountered on axis I. This leads to the conclusion
      that personality disorders increase the risk of substance abuse, that substance
      abuse increases the risk of homelessness, that dual diagnosis has a high impact
      on homelessness and underlines interactions between personality disorders (PD),
      drug abuse (DA) and homelessness. The aim of this paper is also to study these
      interactions. METHOD: We will process the classical epidemiological measures,
      which have already produced interesting findings on other substance-linked
      disorders. We will study the multiplicative interaction (I(AB)) and the
      etiological fraction (EFi) linked to interaction, which evaluate the effects of
      two factors on another. According to the authors, the I(AB) determines whether
      the co-occurrence of two risk factors in a group induces more cases than each
      factor acting together; also if the I(AB) is greater than 1 it is possible to
      estimate the EFi, that proportionally measures the number of cases of the third
      factor that can be attributed to the co-occurrence. We will also study the
      interactions of homelessness and PD on DA, of the PD and DA on homelessness, and
      of this association DA and homelessness on PD. The data we will use in the paper
      deal with the prevalence of PD in general, drug users (n=226), homeless (n=999)
      and homeless drug abusers (n=212). The two last data are extracted from the same
      population and have been collected through clinical interviews, and the diagnosis
      follows the DSM criteria. They are comparable to Kokkevi et al.'s sample
      regarding the drug (heroin), the mean age (28 years for Kokkevi et al., 27 years
      in our sample), and the geographic origin of the populations (Mediterranean
      basin). RESULTS: The repartition of PD differs significantly (0.001) in the
      homeless population and the homeless drug abusers (chi(2)=70.5, df=20).
      Therefore, the intensity of this link is low (rphi=0.30), which is a consequence
      of the high prevalence of PD in the homeless population (80% versus 10% in
      general population). On the other hand, the reparation of PD in the homeless drug
      abusers sample and Kokkevi et al.'s drug abusers is different at 0.001
      (chi(2)=92.64, df=20). The link is high (rphi=0.45) and could be interpreted as a
      supplementary effect of PD's linked to homelessness and in the PD linked to DA,
      thus motivating further exploration of the interactions. The comorbidity DA/PD
      multiplies by 7 the risk of homelessness and explains 46% of the cases of
      homelessness of our sample (n=212). According to table 4, the association
      PD/homelessness multiplies by 13 the risk of DA and explains three-quarter of the
      cases of DA in the personality-disordered homeless people. Moreover, PD appear as
      basic in the etiopathology of such a morbid constellation since the frequency of
      their observation is independent of the association homelessness/DA. These
      findings rejoin the outcomes of similar studies on other addictions. DISCUSSION:
      It could be objected that our sample of homeless men presents a high prevalence
      (20%) of DA; therefore agreeing with epidemiological works on the homeless
      population. The results could be discussed regarding other outcomes in drug
      abuser populations, in which a higher prevalence of PD has been found. Hence, the
      main results concerning interactions would not change and would have still led to
      the conclusion that PD are not influenced by the association homelessness/DA.
      This does not mean that neither homelessness nor DA have an impact on PD. Indeed,
      some authors have shown that there are variations in drug users' PD or in the
      neuropsychological effects of drugs. According to this and to the theory of a
      central role of PD in substance abuse, PD could influence drug use and be
      increased by the abuse. This hypothesis should be tested in another study.
      CONCLUSION: Clinically, the association between DA and PD in homeless populations
      is a major concern regarding the future of these persons. This paper leads to the
      conclusion that the association PD/homelessness is a risk factor for DA, as is
      the dual diagnosis PD/DA for homelessness. In other words, in the case of PD, the
      DA increases the risk of homelessness, which is a risk factor for DA. Lastly,
      these findings confirm the interest of therapeutic approaches focused on PD.

PMID- 19853719
TI  - [Perception and use of an electronic medical record system by professionals of a
      public psychiatric hospital].
AB  - OBJECTIVES: The aim of this study was to evaluate the interest taken by the
      health care providers in the electronic medical file and its use within the
      quality improvement process. SETTING: Our institution is a 204-bed psychiatric
      hospital, employing 328 professionals and comprising three sectors: six units of
      complete hospitalisation (102 beds), one unit of week hospitalisation (15 beds),
      one unit of emergency (7 beds) and one unit of night hospitalisation (15 beds).
      Three extrahospital structures include the day hospitalisation (65 places), the
      medicopsychological centers (CMP) and the part-time therapeutic reception centers
      (CATTP) of the three sectors. METHODS: We conducted face-to-face, semi-structured
      interviews with health care providers of a public psychiatric hospital. All the
      solicited people agreed to answer the investigation. The interviews were
      conducted until no new ideas emerged in the content analysis performed in real
      time, comprising 60 care providers: 10 psychiatrists, 42 nurses and eight
      paramedical professionals. Content analysis was performed by two members of the
      steering committee who were skilled in textual analysis. A descriptive analysis
      was also performed. The variables were described by proportions and means. The
      proportions were compared using the Chi-squared test or Fisher exact test where
      appropriate. A two-tailed P-value of greater than 0.05 was considered to indicate
      statistical significance. Statistical analyses were carried out using SPSS
      version 13.0. RESULTS: Ninety-six percent of the interviewed subjects used the
      electronic medical file. The average number of daily use was seven (S.D.=5).
      Sixty-seven percent had a favorable opinion of the electronic medical file.
      Physicians had more frequent favorable opinions than nurses who considered that
      electronic medical files cannot capture real nursing activity. Health care
      providers considered that electronic medical file could be associated with
      improved quality of care, but two points should be taken into account: the
      increased documentation time (slow system response, multiple screens, the lack of
      computer knowledge, the absence of bedside documentation technology...) and
      dysfunctions in the information processing system. This could have an impact on
      documentation completeness, and quality and could also lead to a reduction of
      time devoted to care. CONCLUSION: This study proposes tracks of improvement in
      the use of the DPIP. In spite of this, a true debate must be initiated on these
      new information systems in psychiatry since their real objectives can be
      perceived as ambiguous, so that programs of clarification, education and
      reinsurance can be set-up.

PMID- 19853720
TI  - [Genetic factors of alcohol-dependence].
AB  - INTRODUCTION: Alcohol dependence is a complex and multifactorial disease
      resulting both from neurobiological mechanisms and environmental factors. It is
      frequently associated with comorbid psychiatric disorders or with specific
      personality or behavioral features. Although action can be taken on the
      environment in order to decrease the risk of the illness, current methods used to
      prevent or to treat this pathology show moderate efficacy: problematic
      consumption of ethanol in the general population as well as relapse rates under
      treatment in dependent patients remain indeed very high. LITERATURE FINDINGS: It
      is therefore of major importance to broaden our knowledge of alcohol dependence
      and its comorbidities so as to improve both their prevention and treatment. In
      this perspective, recent progress in the field of neurosciences may contribute to
      achieve this goal. Precisely, genetics is a promising way benefiting from many
      advances in genetic epidemiology, cellular and molecular biology, neuroimaging
      and pharmacology. In parallel with a better understanding of the neurobiology of
      addictions and associated behaviors, these techniques led to the identification
      of brain mechanisms in which a genetic variation may influence the individual
      vulnerability towards alcohol dependence. Moreover, there is growing evidence
      that alcoholism results from the interaction of genetic and environmental factors
      influencing both its expression and its course. Given the fact that alcohol
      dependence seems highly heritable (50 to 60% of the variance in both men and
      women), this review assesses the role of some of the genomic regions linked with
      the disease, as well as the principal variants of candidate genes identified as
      specifically involved in the predisposition. Polymorphisms of genes influencing
      alcohol metabolism, GABAergic, dopaminergic and serotonergic neurotransmission
      seem, indeed, at stake in the development of alcohol-dependence and its related
      features such as personality, behavior, impulse control or craving. In the
      future, a better characterization of the links between genotypes and phenotypes
      will probably increase our ability to treat alcoholic patients.

PMID- 19853721
TI  - [Ten-year psychosocial outcome of 29 adolescent suicide-attempters].
AB  - OBJECTIVES: This study investigates the psychosocial outcome of adolescents
      admitted to the Nancy University Children's Hospital between the 1st January 1996
      and 31st December 1996 following a suicide attempt, and the influence that the
      initial characteristics (personal, familial and social) of these patients can
      have on their long-term outcome. Defining prognostic factors for a long-term
      negative outcome in young suicide-attempters will enable us to focus our
      therapeutic approach on long-term prevention, as opposed to simple crisis
      management. METHODS: Longitudinal study conducted in 2006 on the basis of self
      questionnaires distributed to former patients and their parents. The self
      questionnaires consisted of 39 questions: 22 questions requiring yes/no answers
      and 12 open questions, 11 of which required a quantitative or objective answer
      (for example, level of education, number of cigarettes consumed, etc.), and one
      of which required a subjective answer (concerning perceived improvements in care
      received), and five satisfaction scales graded from 1 to 10 for the different
      parameters considered, on which responders were asked to make a cross. The
      questions were grouped into three main categories: family life, professional
      status and education, and finally physical and mental health. Patients were also
      asked to answer a second self-questionnaire, the Center for Epidemiologic Studies
      Depression scale (CES-D), which provides an objective assessment of psychological
      well-being. Composed of 20 items (16 presented in negative form and four in
      positive form), this test measures the frequency of symptoms experienced in the
      past week. Symptom frequency is graded from 0 to 3; possible scores therefore
      range from 0 to 60. In France for adults, the depression threshold is considered
      to be 17 in men and 23 in women. The data collected from the different self
      questionnaires was then cross-matched with the personal, familial and social
      characteristics recorded in the former patients' medical and social case notes,
      taken at the time of their suicide attempt in 1996. RESULTS: It was possible to
      trace 67.2% of the former patients and 67.4% of these answered the
      questionnaires, i.e. 45.3% of the initial population. The psychosocial outcome of
      the former patients in our study was quite encouraging, with over three quarters
      of former suicide-attempters stating they were happy in their personal lives, and
      more than half of the 65.5% actually working considering themselves to be
      satisfied or very satisfied with their professional lives. In addition, 66.7% of
      responders did not report any particular psychiatric problem. However, one
      patient completed suicide in the course of 1996. 17.2% of the former patients
      responding to the questionnaire reported a chronic psychiatric condition,
      sometimes accompanied by repeated suicide attempts, and 13.8% situated themselves
      somewhere in between. Learning difficulties and falling behind at school were
      evidenced as risk factors for recurrence, and personal psychiatric antecedents
      were evidenced as factors for poor psychosocial outcome. However, other factors,
      such as personal suicide attempt antecedents, were not evidenced as risk factors
      for poor psychosocial outcome. CONCLUSION: The psychosocial outcome of the former
      patients in our study was quite encouraging. Suicide-attempters who relapsed,
      those who had had more school difficulties, and those who experienced a less
      favourable ten-year psychosocial outcome, had more personal psychiatric
      antecedents.

PMID- 19853722
TI  - [Impact of interferon alpha immunotherapy on tryptophan metabolism in patients
      with chronic hepatitis C. Results of a pilot studies on ten patients].
AB  - INTRODUCTION: The proinflammatory cytokine interferon (IFN) alpha is commonly
      used in the treatment of patients with hepatitis C but its administration is
      often responsible for neuropsychiatric side effects (low mood, fatigue, sleep
      wake disorders, irritability and weight loss). Various mechanisms have been
      incriminated to explain the production of depression and anxiety symptoms, among
      which serotonergic hypothesis is supported by a growing body of evidence. The
      latter posits that IFN-alpha is responsible for central serotonin (5-HT)
      depletion by deviating its precursor, tryptophan (TRP), to a catabolic kynurenine
      (KYN) pathway through induction of indoleamine 2.3 dioxygenase (IDO). The aim of
      the study was to examine the time variation of 5-HT blood (serum and platelet)
      levels and serum KYN/TRP ratio along with instauration of IFN-alpha therapy and
      to correlate these biological variations with mood fluctuations. METHOD:
      Patients. Ten patients (mean [S.D.] age 45 years [12.7], range 29-63; three
      males, seven females) with chronic hepatitis C eligible to receive IFN-alpha
      (1.5microg/kg/week Viraferon, Schering-Plough, administered subcutaneously) were
      recruited from the Gastroenterology department of the University hospital of
      Lille, France. Patients with cirrhosis, HIV or hepatitis B or D co-infection,
      persistent intravenous addiction, corticoid therapy or any DSM-IV axis 1
      psychiatric disorder (diagnosed with MINI interview) were excluded. Patients with
      chronic active hepatitis C were assessed at baseline and monthly during the first
      semester of IFN-alpha and ribavirine bi-therapy. Measurements. The Montgomery
      Asberg Depression Rating Scale (MADRS) and the Hamilton Rating Scale for Anxiety
      (HAM-A) were used to assess depression and anxiety fluctuations. Serum and
      platelet serotonin levels were determined by HPLC with coulometric detection.
      Simultaneous quantification of TRP and KYN was determined by means of HPLC with
      fluorescence detection (TRP) or UV detection (KYN). Statistics. TRP, KYN
      concentrations and KYN/TRP ratio as well as MADRS and HAM-A measurements were
      performed at three time points (day 1, weeks 4 and 12) of IFN-alpha therapy.
      Analysis of variance used a linear model (with subject as the random factor) and
      correlation between measurements used an autoregressive model of order 1. For all
      probabilities, the level of significance was set at P<.05. RESULTS: Two patients
      were excluded before the first post-treatment assessment (results not shown). In
      the eight remaining patients, we observed significant increase of KYN/TRP ratio
      from baseline to early (week 4) and late (week 12) assessments (respectively,
      mean [S.D.] 5.57[5.24], 13.52[15.53] and 29.78[14.11], with P=.04). Similarly,
      significant increase in the MADRS (respectively 7.13[5.2], 12[6.9] and 16.6[8.6],
      with P=.03) and HAM-A (respectively 9.25[6.27], 15.1[6.95] and 18.7[6.27], with
      P=.02) mean scores were observed. Serum and platelet serotonin levels showed no
      significant variation with time. CONCLUSION: The results are consistent with the
      physiopathological hypothesis of an induction of IDO underlying depressive and
      anxiety symptoms related to IFN-alpha therapy in patients with chronic active
      hepatitis C. Nevertheless, this pilot study allows no firm conclusion since
      sample effective is weak and delay between IFN-alpha weekly injection and
      psychiatric and biological assessment was not controlled and thus may have biased
      our findings. However, these encouraging results advocate for further exploration
      of tryptophan metabolism for a better understanding of individual vulnerability
      to IFN-alpha-induced psychiatric adverse effects.

PMID- 19853723
TI  - [Emotional reactivity in euthymic bipolar patients].
AB  - BACKGROUND: Euthymic states in bipolar disorders are usually considered to be
      lacking serious psychiatric disorders. Moreover, recent results prove the need to
      take an interest in a potential emotional dysregulation during these intercrisis
      periods. Therefore, it seems relevant not only to focus on the emotions tonality
      (sadness/euphoria) felt by patients, but also on the intensity of their emotional
      background. Several reasons argue for a disturbance of emotional reactivity in
      euthymic bipolar patients. First, most bipolar patients spontaneously claim they
      have a higher sensitivity than average, which may lead to extreme emotional
      reactions, even during intercrisis periods. Secondly, the emotional reactivity is
      a way to raise the question of the bipolar patients' vulnerability to stress in
      euthymic periods. Several studies have shown the impact of stressful life events
      on the rate of relapse into bipolar disorders. The aim of this study is to
      examine the emotional reactivity of euthymic bipolar patients in comparison with
      a control group, using a test of emotional induction. Our hypothesis is that
      euthymic bipolar patients have a higher emotional reactivity than controls.
      METHOD: One hundred and forty-five subjects were recruited: 90 controls and 55
      euthymic bipolar patients. The patients were interviewed by a trained
      psychologist using the French version of the DIGS providing DSM-IV diagnosis. The
      euthymic state was confirmed with both MADRS (score<12) and Bech's Manic Scale
      (score<4). The subjective emotional reactivity of the subjects was assessed using
      a method of emotional induction, based on viewing a set of 18 (positive, negative
      or neutral) pictures. The subjects have to appreciate the valence (pleasant,
      neutral or unpleasant thoughts) and assess the arousal (degree of emotion
      triggered by each picture). RESULTS: On average, euthymic bipolar patients report
      the same valence and arousal to positive (F [1.143]=0.18, p=0.68) and negative (F
      [1.143]=0.52, p=0.47) pictures as control subjects. Neutral pictures, however,
      were considered more pleasant and moving by euthymic bipolar patients than by
      control subjects (F [1.143]=8.40, p=0.004). CONCLUSION: Euthymic bipolar patients
      seem to present an emotional hyperactivity which occurs especially in neutral
      situations. These results partly corroborate outcomes of other authors, while
      providing a new methodology through the emotional induction test. The highlight
      of emotional hyperreactivity during intercrisis periods allows us to understand
      differently the topic of specific vulnerability to stress of bipolar patients.
      This hypersensitivity could lead to thymic decompensations and could be linked
      with an emotional dysregulation, potential endophenotype of the bipolar
      pathology. Beyond the interest in understanding the physiopathology of the
      bipolar disorder, it could be associated with several clinical applications as
      well as in the psychoeducational field and in the screening of the individual
      risk within the family of bipolar subjects.

PMID- 19853724
TI  - [The case of temporal lobes dysfunction in atypical psychiatric episodes].
AB  - CASE-REPORT: A thirty-seven-year-old man, with temporal epilepsy, had transient,
      atypical psychiatric states with periods of time without any symptom. These
      episodes included hypersexuality with qualitative changes of sex drive, obscene
      behavior, exhibitionism, masturbation and modified sexual orientation. Blunted
      affect, inability to recognize significant persons (visual agnosia) were also
      detected. Magnetic resonance imaging was normal and interictal single-photon
      emission computed tomography (SPECT) showed decreased cerebral perfusion in both
      temporal lobes. DISCUSSION: The principal hypothesis is a Kluver-Bucy syndrome
      (KBS). In animals and human beings, this syndrome can be produced by bilateral
      temporal lobectomy. It is characterised by hypersexuality, visual agnosia, strong
      oral tendency, dietary changes, hypermetamorphosis and blunted affect. A minimum
      of three KBS elements suggests bilateral temporal dysfunction and supports the
      diagnosis. The syndrome may occur in herpes encephalitis, head trauma, Pick
      disease and temporal epilepsy. A single case of a patient, without any evidence
      for structural lesion in temporal lobes, is presented with many KBS symptoms,
      behavioral changes being due to complex partial seizure. Bitemporal dysfunction
      for this patient was confirmed by SPECT scan. On the other hand, the detected
      behavioral changes cannot be explained by temporal epilepsy alone. Postictal
      hypersexuality in temporal epilepsy consists in sexual arousal but not sexual
      aberrations as found in KBS. CONCLUSION: KBS following complex partial status
      epilepticus is a rare phenomenum. The case described here shows how atypical
      psychiatric episodes can cover complex neurologic disorders.

PMID- 19853725
TI  - [Aripiprazole induced Parkinsonism: A case report].
AB  - INTRODUCTION: Aripiprazole is an atypical antipsychotic with a pharmacological
      profile, different from other atypical antipsychotics. It is a high-affinity
      partial agonist at the dopamine D2 and serotonin 5-HT1A receptors and an
      antagonist at serotonin 5-HT2 receptors. It is associated with a good safety and
      tolerability profile including extrapyramidal side-effects. CASE-REPORT: We
      report on a 37 year-old female patient with paranoid schizophrenia who developed
      Parkinsonian symptoms after one month of aripiprazole 10mg per day. She had been
      admitted to our unit for a psychotic episode with delusions of persecution and
      grandiosity. It was her second hospitalization. During the first hospitalization,
      seven years earlier, she had been treated with haloperidol. We do not have any
      information about the tolerability of that treatment. At the start, she received
      olanzapine with good tolerability but without efficacy on psychotic symptoms.
      After 4 weeks, we switched from olanzapine to risperidone 6 mg per day. After a
      few days, the patient developed severe Parkinsonian symptoms. We reduced the dose
      to 4 mg per day without any effect on the extrapyramidal symptoms.We decided to
      discontinue risperidone and to introduce aripiprazole 10mg per day. After one
      month, the patient developed severe Parkinsonian symptoms including hypertonia,
      akinesia, and shuffling gait. After reduction of the dose of Aripiprazole to 5mg
      per day, all the Parkinsonian symptoms had disappeared within 5 days without any
      other medication. DISCUSSION: Few reports of Parkinsonian symptoms with
      aripiprazole have been published in the adult population. There is one report of
      Parkinsonian symptoms, associated with hypersalivation without akathisia, in a
      patient treated with 30 mg per day of aripiprazole. All the symptoms disappeared
      after a switch to olanzapine. The other cases have been reported when
      aripiprazole was associated with anti-depressant serotonin specific reuptake
      inhibitors or serotonin-norepinephrine reuptake inhibitors. One report has been
      published of a 16 year-old girl who had already developed extrapyramidal symptoms
      with olanzapine and risperidone. Another has been published concerning a 3 year
      old child who had taken a half tablet of aripiprazole 15 mg. CONCLUSION: We
      hypothesise that cytochrome P450 2D6 is implicated in this case-report because it
      is active in metabolizing aripiprazole. This patient could have been deficient in
      this enzyme, thus failing to metabolize aripiprazole at a normal rate.

PMID- 19853726
TI  - [Comparative efficacy and acceptability of new-generation antidepressants.
      Synthesis meta-analysis Cipriani].
AB  - Conventional meta-analyses have shown inconsistent results for efficacy of new
      generation antidepressants. The authors therefore did a multiple-treatments meta
      analysis, which accounts for both direct and indirect comparisons, to assess the
      effects of 12 of these antidepressants. They systematically reviewed 117
      randomised controlled trials (25,928 participants), which compared any of the
      following antidepressants for the acute treatment of unipolar major depression in
      adults: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine,
      milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine.
      The main outcomes were the proportion of patients who responded to or dropped out
      of the allocated treatment. Analysis was done on an intention-to-treat basis.
      Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more
      efficacious than duloxetine, fluoxetine, fluvoxamine, paroxetine, and reboxetine.
      Escitalopram and sertraline showed the best profile of acceptability, leading to
      significantly fewer discontinuations than did duloxetine, fluvoxamine,
      paroxetine, reboxetine, and venlafaxine. Clinically important differences exist
      between commonly prescribed antidepressants for both efficacy and acceptability
      in favour of escitalopram and sertraline.

PMID- 19853728
TI  - [Psychological factors and quality of life after percutaneous transluminal
      coronary angioplasty].

PMID- 19853729
TI  - From ST-elevation myocardial infarction to ST elevation with no myocardial
      infarction--review and overview of a new horizon of computerized
      electrocardiographic ischemia detection using high-fidelity implantable devices.
AB  - ST-segment elevation is the clinical hallmark of ST-elevation myocardial
      infarction; however pathophysiologically ST elevation occurs in association with
      acute coronary occlusion long before any myocardial necrosis occurs, for example.
      with no myocardial infarction (MI). The clinical utility of these laboratory
      observations has previously been limited; however, with the advent of permanently
      implantable high-fidelity electrocardiogram monitors, such utility constitutes a
      new horizon for high-risk patients. Rapidly progressive changes in the
      endocardial electrogram, with real-time alarms, could shift the timing, and hence
      the paradigm of care from interruption of MI to prevention of MI.

PMID- 19853730
TI  - New material for implantable cardiac leads.
AB  - Cardiac function management devices, including implantable pacemakers and
      implantable defibrillators, include at least 1 cardiac lead having an electrode
      for making contact with a portion of the heart. It has been previously shown that
      the braided multifilament wire electrodes have a high failure rate both for
      sensing of spontaneous heart activity and for safe heart stimulation. Therefore,
      it is desirable to have cardiac leads made of materials with mechanical and
      electrical properties to insure safe pacemaker function. We have developed a new
      fiber material suitable for implantable cardiac leads with superior high modulus,
      high mechanical strength, and excellent electrical conductivity. METHODS: The
      material comprises poly(p-phenylene benzobisoxazole) fibers plated with gold by
      using an electroless plating method. Due to the difficulty in plating gold
      directly on organic and inorganic fibers, gold plating was carried out on the
      surface of silver-plated fibers. RESULTS: The morphology of plated fibers was
      studied by x-ray diffraction, scanning electron microscopy with energy dispersive
      spectroscopy, and electrochemical polarization measurements. It was found that
      gold was uniformly plated on the poly(p-phenylene benzobisoxazole) fiber, and the
      gold-plated fibers have good corrosion resistance. The electrical conductivity of
      the gold-plated fibers was higher than 4 x 104 S/cm, and its tensile strengths
      and Young moduli were greater than 1.9 and 130 GPa, respectively, when estimated
      in terms of a single-fiber strand. CONCLUSIONS: The metal-clad polymer fibers
      have advantages over conventional metal cardiac leads in flexibility, weight
      savings, mechanical strength, durability, and tailored electrical conductivity.
      Therefore, the combined engineering properties of the new fiber afford
      implantable cardiac lead applications at reduced diameter while having higher
      strength. Furthermore, the new fiber can be terminated just like a regular metal
      wire with the choice of ultrasonic bonding, crimping, or band connection.

PMID- 19853731
TI  - Risk prediction by heart rate turbulence and deceleration capacity in
      postinfarction patients with preserved left ventricular function retrospective
      analysis of 4 independent trials.
AB  - BACKGROUND AND AIM: In the Improved Stratification of Autonomic Regulation-Risk
      trial, postinfarction patients with severe autonomic failure (SAF)-defined as
      abnormal heart rate turbulence in the presence of abnormal deceleration capacity
      (DC)-were at high risk of subsequent death, even if left ventricular function was
      not particularly compromised. The aim of this study was to investigate SAF as a
      risk predictor in independent postinfarction cohorts. METHODS AND RESULTS: The
      data of 3 postinfarction trials (ie, St George's Hospital Medical School
      Postinfarction Survey, Holter substudy of the European Myocardial Infarction
      Amiodarone Trial with both the placebo and the amiodarone arms, and Multiple Risk
      Factor Analysis Trial) were reanalyzed in a blinded fashion. The populations
      included a total of 2534 postinfarction patients. Heart rate turbulence and DC
      were obtained from 24-hour Holter recordings. Patients with both abnormal heart
      rate turbulence (slope < or =2.5 ms/R-R and onset > or =0%) and abnormal DC (< or
      =4.5 milliseconds) were considered suffering from SAF and prospectively
      classified as high risk. Primary end point was all-cause mortality. During follow
      up, 291 of 2534 patients died. In all populations, SAF was a highly significant
      predictor of death in the subgroups of patients with preserved left ventricular
      ejection fraction (LVEF; >30%). The mortality risk of these patients was not
      statistically different from that of patients with impaired LVEF (< or =30%). The
      combined use of the criteria, LVEF of 30% or less and LVEF of more than 30% as
      well as SAF lead to a significant increase of sensitivity in all populations,
      whereas the positive predictive accuracies were preserved. CONCLUSION: In
      postinfarction patients with preserved left ventricular function, SAF identifies
      a subgroup with increased mortality risk equivalent to patients with LVEF of 30%
      or less.

PMID- 19853732
TI  - Laparoscopic total esophagogastric dissociation.
AB  - The total esophagogastric dissociation (Bianchi's procedure) is used to control
      the severe gastroesophageal reflux in patients after failure of the
      fundoplication techniques. The laparoscopic approach can be usefully performed in
      patients with impaired respiratory function. We report here 2 patients in whom
      the total esophagogastric dissociation has been entirely performed by
      laparoscopy. The laparoscopic examination of the proximal esojejunal anastomosis
      is made feasible using an intestinal clamp placed to avoid the esophageal
      retraction up into the posterior mediastinum. The principal complication after
      this surgery is the risk of internal hernia.

PMID- 19853733
TI  - Primary intestinal lymphangiectasia successfully treated by segmental resections
      of small bowel.
AB  - Primary intestinal lymphangiectasia is a rare cause of protein-losing enteropathy
      and usually presents with intermittent diarrhea or malnutrition. Diagnosis
      depends largely on its pathologic condition demonstrating greatly dilated
      lymphatics mainly in the lamina propria of the mucosa. We report a case of
      primary intestinal lymphangiectasia, of the diffuse type, presenting with
      abdominal pain and voluminous diarrhea in a previously healthy 8-year-old boy. He
      had periumbilical pain for 3 months before presentation. He was managed by
      segmental bowel resections and end-to-end anastomoses. The histopathologic
      condition of the resected small intestine showed lymphatic dilation limited
      mainly to the subserosa and mesentery but was not prominent in the mucosa.
      Abdominal pain and diarrhea subsided postoperatively. The present case is the
      fourth report describing a response to operative resection.

PMID- 19853734
TI  - Congenital intrahepatic arterioportal fistula presenting as severe undernutrition
      and chronic watery diarrhea in a 2-year-old girl.
AB  - Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension
      in young children. We report the case of a 2-year-old girl with severe
      undernutrition, chronic watery diarrhea, and gastrointestinal bleeding because of
      a congenital intrahepatic arterioportal fistula. Radiographic embolization and
      surgical ligation of the left hepatic artery were attempted, with no resolution
      of the symptoms. So, a left lobectomy was performed, with excellent results and
      prompt disappearance of the diarrhea. Hepatectomy should be considered as a
      definitive and reliable therapy for congenital IAPF.

PMID- 19853735
TI  - Downsizing to resectability of a large solid and cystic papillary tumor of the
      pancreas by single-agent chemotherapy.
AB  - Solid and cystic pseudopapillary tumor (SCPT) is an uncommon cancer that
      typically affects young women. Most patients with SCPT have a favorable prognosis
      provided a complete resection is attained. There are anecdotal reports of the use
      of neoadjuvant chemotherapy or radiation therapy for patients with unresectable
      tumors. We report the case of a 14-year-old female with SCPT who was successfully
      downsized with gemcitabine before definitive surgical resection.

PMID- 19853736
TI  - H-type rectovaginal fistula in a patient with bilateral single ectopic ureters.
AB  - Congenital H-type rectovaginal fistulas and single ectopic bilateral ureters are
      each rare malformations. We describe a baby girl with a congenital rectovaginal
      fistula diagnosed 2 years after correction of single ectopic bilateral ureters.
      To our knowledge, this is the first association of these entities. Repair of
      fistula was complicated by recurrence, requiring a second procedure. The
      recommended operation for this anomaly requires separating the suture lines on
      the vagina and rectum. The practice of simply oversewing and then buttressing the
      suture lines is probably not sufficient.

PMID- 19853737
TI  - Management of a traumatic hepatic artery pseudoaneurysm and arterioportal fistula
      with a combination of a stent graft and coil embolization using flow control with
      balloon remodeling.
AB  - We describe a child who presented with a traumatic hepatic artery pseudoaneurysm
      and arterioportal fistula, which were subsequently managed with an endovascular
      stent graft and coil embolization using flow control with balloon remodeling.
      This case demonstrates a rarely seen condition in the pediatric population and a
      novel management strategy, which should be considered in the management of this
      complex injury.

PMID- 19853738
TI  - Infant botulism mimicking Hirschprung's disease.
AB  - We report a case of infant botulism presenting as primary colonic ileus-
      mimicking Hirschprung's megacolon. Infant botulism should be considered in any
      infant with constipation and neurologic abnormalities.

PMID- 19853739
TI  - An extremely rare abnormality of a double tracheoesophageal fistula without
      atresia of the esophagus; a case report and review of the literature.
AB  - Tracheoesophageal fistulas without atresia of the esophagus are rare
      abnormalities of the upper gastrointestinal tract with an incidence rate of
      between 1% and 5%. Even more infrequent are 2 tracheoesophageal fistulas without
      atresia of the esophagus. This case report illustrates the history of an infant
      with 2 tracheoesophageal fistulas. The corresponding literature was reviewed, and
      a diagnostic algorithm was described.

PMID- 19853740
TI  - Morbidity in obese adolescents who meet the adult National Institutes of Health
      criteria for bariatric surgery.
AB  - PURPOSE: Some have suggested that the criteria for weight loss surgery in
      adolescents be stricter than those currently recommended for adults by the
      National Institutes of Health (NIH). The aim of the current study is to define
      the characteristics of adolescents who meet NIH consensus criteria for bariatric
      surgery in adults to determine their level of morbidity. MATERIALS AND METHODS:
      Using the Medical Expenditure Panel Survey 2000-2004, children designated as
      meeting NIH criteria were 13 to 17 years of age with (1) a body mass index >or=40
      or (2) a body mass index >35, and one or more comorbidity. We contrasted surgery
      candidates with noncandidates. We examined items that comprise a screener for
      identifying children with special health care needs. The Columbia Impairment
      Scale (CIS) was used to assess child functioning. RESULTS: There were 134
      children identified as candidates for bariatric surgery and 4736 noncandidates in
      the same age range. Candidates were more likely to have special health care needs
      (36% vs 23%) and more likely to have a CIS above 16 (34% vs 16%). Candidates for
      weight loss surgery were 2.36 times as likely to have a CIS score of 16 or higher
      and 1.87 times as likely to be identified as a child with special health care
      needs (P <or= .001). CONCLUSIONS: We conclude that adolescents who meet NIH
      consensus criteria for weight loss surgery in adults require specialized health
      services and have functional impairment. Thus, we advocate the use of the
      standard adult criteria defined by the NIH as the initial screening requirements
      so that enhanced access to weight loss surgery for morbidly obese adolescents may
      be achieved.

PMID- 19853741
TI  - Long-term follow-up of children with extrahepatic portal vein obstruction: impact
      of an endoscopic sclerotherapy program on bleeding episodes, hepatic function,
      hypersplenism, and mortality.
AB  - BACKGROUND: Endoscopic sclerotherapy (ES) has been the standard treatment for
      children with idiopathic extrahepatic portal vein obstruction (EHPVO).
      Portosystemic shunts are indicated when variceal bleeding cannot be controlled by
      ES. Recently, mesenteric left portal vein bypass was indicated as a surgical
      intervention and preventative measure for hepatic dysfunction in children with
      long-term EHPVO. Nevertheless, there is a lack of published data confirming the
      extent of hepatic dysfunction, hypersplenism, and physical development in
      children with long-term follow-up. METHOD: We retrospectively verified the long
      term outcomes in 82 children with EHPVO treated with ES protocol, focusing on
      mortality, control of bleeding, hypersplenism, and consequent hepatic
      dysfunction. RESULTS: Of the children, 56% were free from bleeding after the
      initiation of ES. The most frequent cause of rebleeding was gastric varices
      (30%). Four patients had recurrent bleeding from esophageal varices (4.6%). Four
      patients underwent surgery as a consequence of uncontrolled gastric varices.
      There were no deaths. Most patients showed good physical development. We observed
      a mild but statistically significant drop in factor V motion, as well as
      leukocyte and platelet count. CONCLUSION: Endoscopic sclerotherapy is an
      efficient treatment for children with EHPVO. The incidence of rebleeding is low,
      and there was no mortality. Children develop mild liver dysfunction and
      hypersplenism with long-term follow-up. Only a few patients manifest symptoms of
      hypersplenism, portal biliopathy, or liver dysfunction before adolescence.

PMID- 19853742
TI  - Apoptosis during the development of pelvic floor muscle in anorectal malformation
      rats.
AB  - PURPOSE: Fecal incontinence and constipation still remain as major postoperative
      complications after procedures for anorectal malformations (ARM). The striated
      muscle complex (SMC) is one of the most important factors that influence
      defecation. Previous studies have demonstrated different degrees of the muscle
      complex dysplasia dependent on the complexity of ARM. To explore the mechanisms
      of maldevelopment of SMC in ARM, apoptosis was investigated during pelvic floor
      muscle development in rat embryos with ARM. METHODS: Anorectal malformations in
      rat embryos were induced by treating pregnant rats with ethylenethiourea on the
      10th embryonic day (E10). Normal and ARM rat embryos from E16 to E21 were serial
      sectioned transversely or sagittally, and SMCs were dissected and snap frozen.
      TdT mediated dUTP Nick Ending Labeling (TUNEL) staining and DNA ladder analysis
      were performed to identify apoptosis and expression of Bax/Bcl-2 were confirmed
      with immunohistochemical staining and Reverse Transcription-Polymerase Chain
      Reaction (RT-PCR) analysis. RESULTS: Hypoplastic and disordered SMC sling shifted
      cephalad, ventrally, and converged inferior to the rectourethral fistula and
      infiltrated connective tissue in ARM embryos. In the normal group, TUNEL-positive
      cells became evident on E17; sporadic positive staining was mainly localized in 2
      areas as follows: the junction area between SMC and bulbocarvernosus muscle and
      posterior to the rectum where bilateral SMC converged. In the ARM group, massive
      positive staining of nuclei was observed from E16 to E21 and was mainly
      distributed in the dorsal part of the SMC. Electrophoresis of DNA samples yielded
      a "ladder" pattern of migration both in normal and the ARM group from E17 to E21,
      the ladders were stronger in the ARM group. In both groups, the expression of
      Bax/Bcl-2 was detectable on E17, the immunoreactivity increased on E19 and E21.
      Compared with the normal group, the expression of Bax was increased, whereas Bcl
      2 was declined in the ARM group. Significant upregulation of Bax messenger RNA
      (mRNA) levels and downregulation of Bcl-2 mRNA levels were observed in ARM
      embryos. CONCLUSIONS: In the current study, abnormal apoptosis and disturbed
      expression of Bax/Bcl-2 were identified during SMC development in ARM embryos. It
      is suggested that precocious, excessive, and dislocated apoptosis might be a
      fundamental pathogenesis for the maldeveloped SMC in ARM rats. The temporospatial
      expressions of Bax/Bcl-2 indicate they may have an important role in the
      regulation of apoptosis of SMC.

PMID- 19853743
TI  - MNX1 (HLXB9) mutations in Currarino patients.
AB  - PURPOSE: The combination of partial absence of the sacrum, anorectal anomalies,
      and presacral mass constitutes Currarino syndrome (CS), which is associated with
      mutations in MNX1 motor neuron and pancreas homeobox 1 (previously HLXB9). Here,
      we report on the MNX1 mutations found in a family segregating CS and in 3
      sporadic CS patients, as well as on the clinical characteristics of the affected
      individuals. METHODS: MNX1 mutations were identified by direct sequencing the
      coding regions, intron/exon boundaries of MNX1 in 5 CS Japanese family members
      and 3 Chinese sporadic cases and their parents. RESULTS: There were 2 novel
      (P18PfsX37, R243W) and 2 previously described (W288G and IVS2 + 1G > A)
      mutations. These mutations were not found in 198 control individuals and are
      predicted to impair the functioning of the MNX1 protein. CONCLUSIONS: The
      variability of the CS phenotype among related or unrelated patients bearing the
      same mutation advocates for differences in the genetic background of each
      individual and invokes the implication of additional CS susceptibility genes.

PMID- 19853744
TI  - Clinical and genetic differences in total colonic aganglionosis in Hirschsprung's
      disease.
AB  - Although apparently the same condition as Hirschsprung's disease (HSCR), total
      colonic aganglionosis (TCA) patients (2%-14% congenital aganglionosis) display
      clinical, histopathologic, and genetic differences that may account for altered
      clinical presentations. PATIENTS AND METHODS: Clinical, radiologic, and
      histologic features of 22 TCA patients of 114 HSCR cases (including 16 kindreds)
      were retrospectively evaluated by chart review. With ethical permission, DNA
      mutation analysis of the RET and EDNRB genes was carried out. Polymerase Chain
      Reaction (PCR) products were screened for genetic variation of by Hetroduplex
      Single Strand conformation polymorphism (HEX/SSCP) analysis and compared with 60
      normal population control samples (20/ethnic groups). The SSCP variants were
      validated with automated sequencing techniques showing conformational variants in
      acrylamide gel. RESULTS: Of the 22 patients, 12 (55%) presented within the first
      28 days of extrauterine life, but 10 presented later with 3 (14%) presenting more
      than 6 months of age. The TCA patients evaluated differed clinically,
      radiologically, and histologically, and misdiagnosis occurred in 23% (5/22).
      Seven patients (32%) were familial-the remainder being nonrelated. Histologic
      features varied, and difficulties in diagnosis occurred in 5 (24%), with unclear
      histologic condition delaying diagnosis in one and a mistaken aganglionic level,
      requiring repeat surgery in two. RET variations were detected in 82% (18/22)of
      TCA as opposed to 33% short segment (S-HSCR) with multiple genetic RET variations
      in 5 (28%). Genetic variations included exon 2 SNPs but less than in S-HSCR. One
      had an isolated RET A4 variation with no other abnormalities. Intronic RET
      variations occurred in intron 6 (2 patients) (IVS6+56delG) and intron 16 (2
      patients) (IVS16-38delG). A cysteine radical mutation (C620R) (2 patients) was
      related to Multiple Endocrine Neoplasia Type 2 (MEN2) in the family. In contrast
      to S-HSCR, genetic variations in TCA aggregated to the important tyrosine kinase
      (intracellular) region in 5 patients suggesting a possible pathogenetic link.
      EDNRB variations occurred in 7 patients (32%) all within exon 4 of the gene.
      CONCLUSIONS: Total colonic aganglionosis differs clinically from other HSCR
      phenotypes and may lead to misdiagnosis. Potential disease-related RET gene
      mutations include exon 17-21 genetic variations that suggest the possibility of
      disrupted downstream signaling pathways from vital gene recruitment sites as
      possible TCA contributing factors.

PMID- 19853746
TI  - Long-term results of anterior sagittal anorectoplasty for the treatment of
      vestibular fistula.
AB  - PURPOSE: Vestibular fistula is the commonest anorectal malformation in the female
      child. This article reports the treatment and long-term follow-up of 1206
      patients of vestibular fistula treated by anterior sagittal anorectoplasty
      (ASARP) in a single center for 38 years. MATERIAL AND METHODS: All patients of
      vestibular fistula admitted and operated on at the Department of Pediatric
      Surgery, King George Medical University (Lucknow, UP India), from 1970 were
      included in the study; the age ranged from 2 days to 40 years. The diagnosis was
      made by clinical examination. We differentiated between anovestibular fistula
      (AVF) and rectovestibular fistula (RVF) in that the latter is a longer narrow
      fistula closely applied to the posterior wall of the vagina. Preoperative
      investigations included hemogram and blood glucose. Echocardiography was done in
      those patients showing a physical sign of cardiac anomaly. All patients were
      operated on in the lithotomy position by ASARP; this was done without colostomy
      in 1169 patients. In 6 patients, preliminary colostomy was done because of
      excessive perineal excoriation, and 31 others had colostomy done elsewhere. The
      striated muscle complex was delineated by electrostimulation, and anoplasty was
      performed after anchoring the rectum within the muscle complex. Washing of the
      perineum after passage of stools with application of povidone-iodine ointment
      constituted the local care. Intravenous antibiotics were administered for 48
      hours and oral antibiotics (including metronidazole) for 5 days. The patient was
      discharged home by the fifth day. RESULTS: Follow-up ranges from 3 months to 19
      years; uneventful postoperative recovery was seen in 1147 patients. They had
      normal growth and development, normal appearance of the perineum, and a normal
      quality of life. Complications were seen in 60 patients (5%) of which 42 had AVF
      and 18 had RVF. Eight patients had postoperative wound disruption that was minor
      in 4 and required colostomy in the other 4. Four patients had recurrence of
      vestibular fistula thus creating an iatrogenic perineal canal; this could be
      repaired by a second ASARP in 3 patients and required colostomy and PSARP in one
      child. Anal stenosis was seen in 11 patients; this was treated by dilatation
      alone in 6 and required posterior Y-V plasty in 5. The rate of complications in
      RVF was lower than AVF probably because of lesser number of patients; there was
      no difference in stooling pattern or continence between uncomplicated patient of
      RVF and AVF; however, fecal staining was seen in all patients undergoing revision
      surgery for complications. CONCLUSIONS: This experience with ASARP showed a good
      result in 95% patients in a single-stage procedure. The technical ease and
      minimal preoperative and postoperative measures make ASARP the procedure of
      choice for vestibular fistula in females at all ages. Until sufficient experience
      is gained, it may be safer to operate on patients with RVF under cover of a
      protective colostomy.

PMID- 19853745
TI  - Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3.
AB  - BACKGROUND: The rearranged during transfection (RET) gene encodes a single-pass
      receptor whose proper expression and function are essential for the development
      of enteric nervous system. Mutations in RET regulatory regions are also
      associated with Hirschsprung disease (HSCR) (aganglionosis of the colon). We
      previously showed that 2 polymorphisms in RET promoter are associated with the
      increased risk of HSCR. These single nucleotide polymorphisms overlap with the
      NK2 homeobox 1 (Nkx2-1) binding motif interrupting the physical interaction of
      NKX2-1 with the RET promoter and result in reduced RET transcription. In this
      study, we further delineated Nkx2-1-mediated RET Transcription. METHODS AND
      RESULTS: First, we demonstrated that PHOX2B, like SOX10 and NKX2-1, is expressed
      in the mature enteric ganglions of human gut by immunohistochemistry. Second,
      subsequent dual-luciferase-reporter studies indicated that Nkx2-1 indeed works
      coordinately with Phox2b and Sox10, but not Pax3, to mediate RET transcription.
      In addition, identification of Phox2b responsive region in RET promoter further
      provides solid evidence of the potential functional interaction between Phox2b
      and RET. CONCLUSION: In sum, Phox2b and Sox10 act together with Nkx2.1 to modify
      RET signaling and this interaction may also contribute to HSCR susceptibility.

PMID- 19853747
TI  - Vulvar lipomas in children: an analysis of 7 cases.
AB  - PURPOSE: Vulvar lipomas are a type of rare benign soft tissue tumor. This study
      describes 7 cases of vulvar lipomas in children, and it evaluates the clinical
      characteristics of this disease. METHOD: We performed a retrospective review of
      pediatric patients at our institution who were diagnosed with vulvar lipomas
      between January 1998 and December 2007. RESULTS: Seven girls who were between the
      ages of 7 and 11 years were included in the study. In 6 cases, the lipomas were
      located on the right side of the vulva. In 4 of those 6 cases, the lipomas were
      found on the right anterolateral side. Five cases had gross swelling of the vulva
      with a poorly demarcated mass, but 2 cases had a well-demarcated or pedunculated
      mass. The initial tentative diagnoses made before imaging studies were right
      inguinal hernia in 4 cases and Bartholin's cyst in 2 cases. Preoperative imaging
      studies of ultrasound, computed tomography, and magnetic resonance imaging showed
      lipomatous characteristics of these tumors. All cases underwent surgical
      excision. Subsequent histopathologic examination demonstrated lipomas in each
      case. CONCLUSIONS: Vulvar lipomas in children tend to occur on the right side,
      especially the right anterolateral side. It is necessary to differentiate this
      tumor from an inguinal hernia. Radiologic studies such as ultrasonography,
      computed tomography, and magnetic resonance imaging are useful for making the
      proper diagnosis. Surgical excision is the treatment of choice.

PMID- 19853748
TI  - Complicated appendicitis in children: is laparoscopic appendectomy appropriate? A
      comparative study with the open appendectomy--our experience.
AB  - PURPOSE: Good outcomes have been reported with laparoscopic appendectomy (LA) for
      uncomplicated appendicitis in children, but the use of laparoscopy for
      complicated appendicitis in children is more controversial. This is related to a
      higher incidence of postoperative abdominal and wound infections. The purpose of
      this trial was to retrospectively compare LA and open appendectomy (OA) for
      complicated appendicitis and evaluate the efficacy of LA in children with
      complicated appendicitis. METHODS: The outcome of 128 patients with complicated
      appendicitis in children was retrospectively analyzed. There were 80 children in
      the LA group and 48 in the OA group. The appendectomies were performed by a
      single senior surgeon and his surgical trainees. There was no selection of cases
      for LA. Data collection included demographics, operative time, resumption of
      diet, infectious complications (wound infection and intraabdominal abscess),
      length of hospitalization, and duration of antibiotic use. RESULTS: There were no
      cases of LA that required conversion to OA. The operative time for LA (88.5 +/-
      28.8 minutes for LA vs 71.8 +/- 30.6 minutes for OA; t = 3.10; P = .002) was
      longer. Patients in the LA group returned to oral intake earlier (1.8 +/- 0.6
      days for LA vs 2.8 +/- 0.8 days for OA; t = -8.04; P < .01) and had a shorter
      length of hospital stay (6.5 +/- 2.2 days for LA vs 7.8 +/- 2.9 days for OA; t = 
      2.87; P = .005). The incidence of wound infection (1/80 [1.3%] for LA vs 6/48
      [12.5%] for OA; P < .05) and postoperative intraabdominal abscess (2/80 [2.5%]
      for LA vs 7/48 [14.6%] for OA; P < .05) in LA group was lower. No significant
      difference was found in the duration of antibiotic administration between the 2
      groups (5.8 +/- 1.8 days for LA vs 6.3 +/- 2.3 days for OA; t = -1.37; P = .174).
      No mortality was observed in either group. CONCLUSIONS: The minimally invasive
      laparoscopic technique is feasible, safe, and efficacious for children with
      complicated appendicitis. Laparoscopic appendectomy should be the initial
      procedure of choice for most cases of complicated appendicitis in children.

PMID- 19853749
TI  - Surgical outcomes of esophageal atresia without fistula for 24 years at a single
      institution.
AB  - PURPOSE: The aim of the study was to evaluate the surgical outcome of esophageal
      atresia (EA) without fistula for 24 years at a single tertiary center for
      pediatric surgery. METHODS: The study used a retrospective chart review of
      infants diagnosed with EA without fistula between 1981 and 2005. RESULTS: Of 33
      patients with EA without fistula, 31 charts were available. Mean birth weight was
      2327 g (range, 905-3390 g), and 71% were male. Most common associated anomalies
      were cardiac (n = 6; 19%) and renal (n = 5; 16%), followed by vertebral (n = 4;
      13%) and anorectal (n = 2; 7%). The median initial esophageal gap was 5 vertebral
      bodies. Six had a primary repair, and 25 patients had esophageal replacement at a
      median age of 7 months. This involved gastric transposition in 20 (1 followed
      failed jejunal interposition), colonic interposition in 5, jejunal interposition
      in 1 (after a failed colonic), and repair at another center in 1. With a median
      review of 9 years, 21 patients had long-term sequelae with the need for multiple
      further surgical procedures including an antireflux procedure in 5. One patient
      died. CONCLUSIONS: Management of EA without fistula remains challenging. Most
      patients required staged treatment that included esophageal replacement. The
      frequency of late complications indicates the need for programmed long-term
      review.

PMID- 19853750
TI  - Prenatal retinoic acid up-regulates pulmonary gene expression of COUP-TFII, FOG2,
      and GATA4 in pulmonary hypoplasia.
AB  - PURPOSE: Retinoids play an important role in lung development. Recently, prenatal
      treatment with retinoic acid (RA) has been reported to stimulate alveologenesis
      in hypoplastic lungs in the nitrofen model of congenital diaphragmatic hernia
      (CDH). Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is
      a transcription factor in the steroid/thyroid hormone receptor superfamily, and
      targeted ablation of COUP-TFII causes CDH and associated lung hypoplasia in mice.
      Friend of GATA 2 (FOG2) is a zinc finger-containing protein that modulates the
      transcriptional activity of GATA proteins. GATA4 is a member of a family of DNA
      binding proteins, which is found in the promoter regions of many genes. The COUP
      TFII, FOG2, and GATA4 genes, regulated by the retinoid signaling pathway, are
      located on chromosomes 15q26, 8q23, and 8p23.1 respectively, regions reported to
      be deleted in individuals with CDH. The aim of this study was to examine the
      pulmonary gene expression of COUP-TFII, FOG2, and GATA4 in the nitrofen model of
      CDH. MATERIALS AND METHODS: Pregnant rats were exposed to either olive oil or 100
      mg nitrofen on day 9 of gestation (D9). 5 mg/kg of RA was given intraperitoneally
      on days D18, D19, and D20. The fetuses were recovered by caesarean section on
      D21, and the diaphragm was carefully examined for the presence of a hernia under
      a microscope. Left lungs were obtained from CDH fetuses and controls and divided
      into four groups: control (n = 9), control + RA (n = 9), CDH (n = 9), and CDH +
      RA (n = 9). The relative mRNA expression levels of COUP-TFII, FOG2, and GATA4
      were analyzed in each lung by real-time reverse transcriptase-polymerase chain
      reaction from cDNA generated by mRNA from pulmonary total RNA. RESULTS: The
      relative mRNA expression levels of COUP-TFII, FOG2, and GATA4 were significantly
      increased in CDH + RA lungs compared to control, control + RA, and CDH (P < .05).
      CONCLUSIONS: Up-regulation of pulmonary gene expression of COUP-TFII, FOG2, and
      GATA4 after prenatal treatment with retinoic acid in the nitrofen model of CDH
      suggests that RA may have a therapeutic potential in modulating lung growth.
      Furthermore, these results support the concept that these proteins work together
      to regulate downstream target genes that play an important role in the
      development of lung.

PMID- 19853751
TI  - Pepsin measured in induced sputum--a test for pulmonary aspiration in children?
AB  - PURPOSE: The purpose of this study was to investigate if pepsin measured in
      sputum is a useful marker of pulmonary aspiration secondary to gastroesophageal
      reflux (GER) in children. It is possible that the induced sputum procedure could
      cause GER and invalidate the results. The hypothesis stated that healthy children
      (those without history of respiratory or gastroesophageal symptoms) would not
      have pepsin detected in induced sputum. METHODS: Children attending surgical
      outpatients in the Royal Belfast Hospital for Sick Children (Belfast, Northern
      Ireland) were recruited. After spirometry, sputum was obtained by induction with
      hypertonic 3% saline. Spirometry was repeated, and complications were noted. An
      "in-house" enzyme-linked immunosorbent assay was used to measure pepsin
      concentration in sputum. The lower limit of detection of pepsin was 1.19 ng/mL.
      RESULTS: Children (n = 21) aged 4 to 16 years were recruited. Twenty children
      completed the study. No adverse effects were reported. Pepsin was detected in 17
      (85%) of 20 sputum samples. CONCLUSIONS: The act of sputum induction appears to
      induce physiologic GER in a healthy childhood population. The analysis of pepsin
      in sputum obtained by sputum induction is therefore not useful in the
      investigation of reflux-related respiratory disease.

PMID- 19853752
TI  - Impact of spinal anesthesia for open pyloromyotomy on operating room time.
AB  - PURPOSE: When pyloromyotomy for hypertrophic pyloric stenosis (HPS) is performed
      under general anesthesia, metabolic abnormalities and fluid deficits coupled with
      residual anesthetics may increase the risk of postoperative apnea, thereby,
      prolonging operating room time and delaying extubation. Spinal anesthesia has
      been found to reduce the rate of postoperative apnea in high-risk infants. The
      aim of the study was to evaluate the effect of spinal vs general anesthesia on
      operating room time in infants undergoing open pyloromyotomy. METHODS: Data for
      60 infants who underwent pyloromyotomy under spinal (n = 24) or general (n = 36)
      anesthesia at a tertiary pediatric medical center were derived from the
      computerized database. Primary outcome measures were total operating room time,
      procedure duration, anesthesia release time, wake-up time, and anesthesia control
      time (anesthesia release plus wake-up). Nonparametric Mann-Whitney test was used
      for statistical analysis, and Levene's test was used to assess the equality of
      variances in samples; P <or= .05 was considered significant. RESULTS: Mean total
      operating room time was 50.9 (12.1) minutes in the spinal anesthesia group and
      69.5 (26.8) minutes in the general anesthesia group (P = .001). Corresponding
      values for mean wake-up time were 3.6 (2.9) and 17.2 (25.3) minutes (P < .001),
      and for mean anesthesia control time, 13.2 (6.7) and 28.5 (24.6) minutes (P <
      .001). There were no between-group differences in procedure duration or
      anesthesia release time. On Levene's test, between-group differences were
      significant for total operating time and wake-up time (P = .01 for both).
      CONCLUSIONS: The use of spinal anesthesia for open pyloromyotomy in infants with
      HPS shortens the operating room time by reducing the wake-up time.

PMID- 19853753
TI  - Outcomes of sutureless gastroschisis closure.
AB  - INTRODUCTION: A new technique of gastroschisis closure in which the defect is
      covered with sterile dressings and allowed to granulate without suture repair was
      first described in 2004. Little is known about the outcomes of this technique.
      This study evaluated short-term outcomes from the largest series of sutureless
      gastroschisis closures. METHODS AND PATIENTS: A retrospective case control study
      of 26 patients undergoing sutureless closure between 2006 and 2008 was compared
      to a historical control group of 20 patients with suture closure of the abdominal
      fascia between 2004 and 2006. Four major outcomes were assessed: (1) time spent
      on ventilator, (2) time to initiating enteral feeds, (3) time to discharge from
      the neonatal intensive care unit, and (4) rate of complications. RESULTS: In
      multivariate analysis, sutureless closure of gastroschisis defects independently
      reduced the time to extubation as compared to traditional closure (5.0 vs 12.1
      days, P = .025). There was no difference in time to full enteral feeds (16.8 vs
      21.4 days, P = .15) or time to discharge (34.8 vs 49.7 days, P = .22) with
      sutureless closure. The need for silo reduction independently increased the time
      to extubation (odds ratio, 4.2; P = .002) and time to enteral feeds (odds ratio,
      5.2; P < .001). Small umbilical hernias were seen in all patients. CONCLUSION:
      Sutureless closure of uncomplicated gastroschisis is a safe technique that
      reduces length of intubation and does not significantly alter the time required
      to reach full enteral feeds or hospital discharge.

PMID- 19853754
TI  - Lack of insurance negatively affects trauma mortality in US children.
AB  - PURPOSE: Uninsured children face health-related disparities in screening,
      treatment, and outcomes. To ensure payer status would not influence the decision
      to provide emergency care, the Emergency Medical Treatment and Active Labor Act
      (EMTALA) was passed in 1986, which states patients cannot be refused treatment or
      transferred from one hospital to another when medically unstable. Given findings
      indicating the widespread nature of disparities based on insurance, we
      hypothesized that a disparity in patient outcome (death) after trauma among the
      uninsured may exist, despite the EMTALA. METHODS: Data on patients age 17 years
      or younger (n = 174,921) were collected from the National Trauma Data Bank (2002
      2006), containing data from more than 900 trauma centers in the United States. We
      controlled for race, injury severity score, sex, and injury type to detect
      differences in mortality among the uninsured and insured. Logistic regression
      with adjustment for clustering on hospital was used. RESULTS: Crude analysis
      revealed higher mortality for uninsured children and adolescents compared with
      the commercially or publicly insured (odds ratio [OR] 2.97; 95% confidence
      interval [CI], 2.64-3.34; P < .001). Controlling for sex, race, age, injury
      severity, and injury type, and clustering within hospital facility, uninsured
      children had the highest mortality compared with the commercially insured (OR,
      3.32; 95% CI, 2.95-3.74; P < .001], whereas children and adolescents with
      Medicaid also had higher mortality (OR, 1.19; 95% CI, 1.07-1.33; P = .001).
      CONCLUSIONS: These results demonstrate that uninsured and publicly insured
      American children and adolescents have higher mortality after sustaining trauma
      while accounting for a priori confounders. Possible mechanisms for this disparity
      include treatment delay, receipt of fewer diagnostic tests, and decreased health
      literacy, among others.

PMID- 19853755
TI  - Outcomes of truncal vascular injuries in children.
AB  - BACKGROUND: Pediatric truncal vascular injuries occur infrequently and have a
      reported mortality rate of 30% to 50%. This report examines the demographics,
      mechanisms of injury, associated trauma, and outcome of patients presenting for
      the past 10 years at a single institution with truncal vascular injuries.
      METHODS: A retrospective review (1997-2006) of a pediatric trauma registry at a
      single institution was undertaken. RESULTS: Seventy-five truncal vascular
      injuries occurred in 57 patients (age, 12 +/- 3 years); the injury mechanisms
      were penetrating in 37%. Concomitant injuries occurred with 76%, 62%, and 43% of
      abdominal, thoracic, and neck vascular injuries, respectively. Nonvascular
      complications occurred more frequently in patients with abdominal vascular
      injuries who were hemodynamically unstable on presentation. All patients with
      thoracic vascular injuries presenting with hemodynamic instability died. In
      patients with neck vascular injuries, 1 of 2 patients who were hemodynamically
      unstable died, compared to 1 of 12 patients who died in those who presented
      hemodynamically stable. Overall survival was 75%. CONCLUSIONS: Survival and
      complications of pediatric truncal vascular injury are related to hemodynamic
      status at the time of presentation. Associated injuries are higher with trauma
      involving the abdomen.

PMID- 19853756
TI  - Body wall and visceral nonrhabdomyosarcoma soft tissue sarcomas in children and
      adolescents.
AB  - BACKGROUND: Predictors of outcome have not been established for pediatric
      visceral and body wall nonrhabdomyosarcoma soft tissue sarcomas (NRSTS). METHODS:
      The study used a retrospective review of clinical features and outcome of 61
      patients with visceral and body wall NRSTS evaluated at our institution between
      March 1962 and December 1999. RESULTS: Median age at diagnosis was 9.9 years
      (range, birth to 17.4 years). Tumors were greater than 5 cm in 43 (70%), high
      grade in 33 (54%), invasive in 25 (41%), and metastatic at presentation in 14
      (23%) patients. Visceral tumors (n = 27) were more likely than body wall tumors
      (n = 34) to be greater than 5 cm (93% vs 53%; P < .001) and invasive (70% vs 18%;
      P < .001) and were less likely to be resected at diagnosis (44% vs 85%; P =
      .001). Estimated 10-year event-free survival (EFS) and overall survival (OS) for
      the entire cohort were 45.5% +/- 6.9% and 56.8% +/- 6.7%, respectively. The 10
      year EFS and OS were better for patients with body wall sites than for those with
      visceral sites (61.8% +/- 8.5% and 67.5% +/- 8.2% vs 24.2% +/- 9.4% and 43.0% +/-
      10.3%; P = .004 and P = .004). The 10-year estimated cumulative incidence (CI) of
      local recurrence was higher for patients with visceral sites than for those with
      body wall sites (64.3% +/- 9.8% vs 26.5% +/- 7.7%; P = .004), whereas CI of
      distant recurrence was similar for the 2 sites (15.2% +/- 7.2% vs 23.5% +/- 7.4%;
      P = .39). CONCLUSIONS: Pediatric patients with visceral NRSTS are more likely to
      have invasive, large, and unresectable tumors compared to those with body wall
      tumors. More than two thirds of visceral NRSTS recur locally, and fewer than half
      of patients with visceral tumors survive.

PMID- 19853757
TI  - Retrospective study of the surgical management and outcome of nonrhabdomyosarcoma
      soft tissue sarcomas of the groin and axilla in children.
AB  - PURPOSE: The incidence of pediatric nonrhabdomyosarcoma soft tissue sarcomas
      (NRSTSs) of the groin and axilla is unknown, and the optimal surgical approach to
      these patients is unclear. METHODS: We conducted a retrospective study of
      patients treated at St Jude Children's Research Hospital from January 1962 to
      March 2007 for NRSTSs of the groin and axilla. Demographic variables, tumor
      pathology, clinical management, and outcome were reviewed. RESULTS: Of the 300
      patients treated for NRSTSs, only 10 had tumors of the axilla or groin (6 of whom
      had synovial sarcoma). Surgical interventions included wide resection of the
      tumor (n = 7), marginal resection (n = 1), subtotal resection (n = 1), and biopsy
      only (n = 1). Six patients underwent lymph node sampling; all were negative for
      tumor. Short- and long-term surgical complications were rare. Four patients
      received adjuvant chemotherapy (n = 3) and/or radiotherapy (n = 2). At a median
      follow-up of 8.5 years, 7 of the 10 were surviving free of disease. Two of these
      patients died of tumor progression (1 with metastases at diagnosis and 1 with an
      unresectable tumor at diagnosis), and one patient who was free of NRSTS died of
      secondary breast carcinoma. CONCLUSIONS: Pediatric NRSTSs of the axilla and groin
      are rare, but outcomes are similar to those of other patients with NRSTS. Wide
      local excision of the tumor with preservation of good limb function should be the
      surgical goal and may be sufficient therapy in some cases.

PMID- 19853758
TI  - Perfusion computed tomography could be a new tool for single-session imaging of
      ureteric obstructive pathology: an experimental study in rats.
AB  - BACKGROUND/PURPOSE: Perfusion imaging redefines computed tomography (CT) as a
      technique that can now depict vascular physiology in addition to detailed
      anatomy. The major clinical applications of perfusion CT are in acute stroke and
      oncology. Currently, there are very limited data on the application of perfusion
      CT in urology. The aim of the present study is to investigate the potential value
      of perfusion CT in anatomic and functional evaluation of obstruction in a single
      session on experimental hydronephrosis model in rats. Thus, we evaluate the
      perfusion CT in a new clinical application. METHODS: Twenty-eight rats were
      randomly allocated into 4 groups each consisting of 7 rats. At the third week of
      experimental intervention, postoperative renogram curves and perfusion parameters
      of the right kidneys' cortex and pelvis were assessed by CT. The right ureter was
      sutured as proximal complete obstruction in group 1, as distal complete
      obstruction in group 2, and as proximal partial obstruction in group 3. Group 4
      served as the sham control group. Computed tomography was performed with single
      slice tomography. Dynamic examination was performed with the help of perfusion
      software through contrast-enhanced tomography examination. RESULTS: In all study
      groups, the aorta time/density curves showed a rapid increase after a rapid
      decrease, and the duration to reach peak concentration in the normal kidney
      cortex was observed to be later than the aorta as expected. In groups 1, 2, and
      3, the duration to reach peak concentration lengthened and the peak concentration
      values decreased. The time/density curves gradually increased as a result of the
      accumulation of the contrast agent in the pelvis, and a peak was observed at the
      end of the procedure in all study groups. In groups 1, 2, and 3, a statistically
      significant decrease (P = .01, P = .01, and P = .01, respectively) was observed
      in the peak concentration values of the contrast agent in comparison to group 4.
      The flow and blood volume values gradually decreased as the grade of the
      obstruction increased and the localization of the obstruction or grade of
      obstruction moved closer to the kidney. CONCLUSION: In conclusion, perfusion CT
      technique, performed in a single session, is a useful method for anatomic
      visualization, together with functional evaluation, in the diagnosis of ureteric
      obstructive pathology of experimental hydronephrosis model.

PMID- 19853759
TI  - Role of magnetic resonance urography in the diagnosis of single-system ureteral
      ectopia with congenital renal dysplasia: a tertiary care center experience in
      India.
AB  - OBJECTIVE: The purpose of this article is to study the role of magnetic resonance
      urography (MRU) in single-system ureteral ectopia with congenital renal dysplasia
      in children. MATERIALS AND METHODS: Patients of incontinence with an otherwise
      normal voiding pattern were investigated by MRU and conventional radiology. All
      the patients underwent laparoscopic nephroureterectomy after MRU. RESULTS:
      Magnetic resonance urography picked up the dysplastic moieties and their location
      as well as functional status and also depicted the course of the ectopic ureter
      in all the 7 patients. CONCLUSION: Magnetic resonance urography is the better
      method of investigation for the diagnosis of this condition than conventional
      radiologic investigations and renal scan.

PMID- 19853760
TI  - Protective effect of erythropoietin on torsion/detorsion injury in rat model.
AB  - PURPOSE: The aim of the study is to investigate the effects of erythropoietin on
      torsion/detorsion injury in rats. METHODS: Forty rats were divided randomly into
      5 groups: group I (sham, S), sham operation; group II (torsion/detorsion 1,
      T/D(1)), 3 hours ischemia and 1 hour reperfusion; group III (torsion/detorsion 2,
      T/D(2)), 3 hours ischemia and 48 hours reperfusion; group IV (erythropoietin 1,
      EPO(1)), 3 hours ischemia, 1 hour reperfusion, and a single dose of EPO; and
      group V (erythropoietin 2, EPO(2)), 3 hours ischemia, 48 hours reperfusion, and 2
      doses of EPO. Malondialdehyde (MDA) and nitric oxide (NO) levels and activities
      of superoxide dismutase and catalase were measured. Tissue damage to ovarian
      tissue was scored by histologic examination. Data were compared among groups with
      parametric tests. RESULTS: The MDA levels in the S and EPO groups were
      significantly lower than the T/D groups (P < .001). Catalase and superoxide
      dismutase activities, and NO levels in the S and EPO groups were significantly
      higher than in the T/D groups (P < .05). Ovarian tissue damage in the S and EPO
      groups was significantly less than in the T/D groups (P < .05). Levels of all
      biochemical markers and ovarian tissue damage scores were similar among the S,
      EPO(1), and EPO(2) groups (P > .05). CONCLUSION: Erythropoietin attenuates
      ischemia-reperfusion injury when given during the acute phase of ovarian torsion
      detorsion in a rat model.

PMID- 19853761
TI  - Effects of grade 1 varicocele detected in the pediatric age-group on testicular
      development.
AB  - PURPOSE: A number of reports have indicated the effectiveness of varicocelectomy
      on large varicoceles in adolescents. We carried out a 5-year follow-up study to
      examine the effect of grade 1 varicocele on testicular development. METHODS: Of
      31 boys with left grade 1 varicocele (mean age, 12.6 years), 10 underwent
      microsurgical varicocelectomy and 21 were conservatively observed and evaluated
      for testicular volume and varicocele grade. The control group consisted of 20
      healthy age-matched boys without a varicocele. The mean relative left testicular
      volume was compared with the right testis and the absolute bilateral testicular
      volumes among the boys in all groups. RESULTS: Of 21 boys who were observed, 13
      (62%) continued to have grade 1 varicocele, 4 (19%) developed grade 2 varicocele,
      and the other 4 boys (19%) showed spontaneous resolution. Twelve testes (57%)
      developed in parallel with the right testis, and 1 boy (5%) who experienced
      spontaneous resolution of the varicocele had catch-up testicular growth, whereas
      8 boys (38%) had left testicular growth delay with or without an increasing grade
      of varicocele. Varicocelectomy, but not observation, improved the previously
      noted testicular growth delay. Furthermore, right testicular growth delay was
      also noted during observation. CONCLUSIONS: More than half of the total number of
      boys with grade 1 varicocele showed normal development, whereas many boys
      presented with growth delay in both testes. Thus, we still need to define
      reliable predictors that will permit selection of the best candidates for
      varicocelectomy.

PMID- 19853762
TI  - Is the Fowler-Stephens procedure still indicated for the treatment of nonpalpable
      intraabdominal testis?
AB  - PURPOSE: There are no formal guidelines for the management of boys with
      nonpalpable testis. In this article, we report our experience in treating all
      nonpalpable intraabdominal testis (NPIT) with standard inguinal orchidopexy
      without dividing the spermatic vessels stating that the Fowler-Stephens technique
      is no longer indicated for the treatment of the intraabdominal testis. METHODS:
      Between June 2003 and April 2008, we treated 23 boys with NPIT confirmed by
      ultrasound or laparoscopy. All cases were treated through an inguinal orchidopexy
      without division of the spermatic vessels by fixing the testis to the scrotum by
      2 absorbable stitches even if there was an upward retraction of the scrotal skin.
      Location and size of testis were reported at 1 week, 1 month, 3 months, and 6
      months through physical examination. RESULTS: Average age at presentation was 24
      months. Ten patients (43%) had the NPIT on the right side, 8 (35%) on the left
      side, and 5 (22%) were bilateral. We had no intraoperative complications. All
      patients were discharged on the same day. In all cases, the testis was normal in
      size and found in the scrotum after 6 months of follow-up. CONCLUSION: On the
      basis of our experience, we believe that the Fowler-Stephens procedure is not
      indicated anymore in the management of NPIT. Orchidopexy without division of the
      spermatic vessels should be the treatment of choice even for the cases of very
      high intraabdominal testis because it does not affect normal testicular
      vascularization and is minimally invasive.

PMID- 19853763
TI  - Etiology of chest wall deformities--a genetic review for the treating physician.
AB  - Chest wall deformities such as pectus excavatum, pectus carinatum, and cleft
      sternum can be isolated malformations or dysmorphic features of genetic
      associations, monogenic disorders, and various numeric and structural chromosomal
      aberrations. In contrast to the most important syndromes such as Marfan syndrome
      or Noonan syndrome that can be associated with a chest wall deformity and for
      which the causative genes are known, etiology of isolated chest wall deformities
      is still a matter of research. Therefore, an interdisciplinary approach,
      particularly in patients with additional symptoms is strongly recommended to
      choose the best therapeutic approach for each patient and its family.

PMID- 19853764
TI  - Iatrogenic Horner syndrome after tube thoracostomy.
AB  - Iatrogenic Horner syndrome is a rare complication of chest tube insertion, with
      little information available on this topic in the pediatric literature. We
      present a case of a 13-month-old boy with a left-sided pneumonia and an
      associated pleural effusion for which a chest tube was inserted. His respiratory
      and septic parameters improved, but he was noted to have ptosis, miosis, and
      anhydrosis of the left side. These resolved in the days after chest tube removal.
      Although tube thoracostomy is a common procedure in surgical practice, little is
      written about the potential for injury to the ipsilateral sympathetic chain. This
      report reviews the available literature, with an emphasis on complication
      avoidance.

PMID- 19853765
TI  - Cystic lymphangioma of the breast in a 6-year-old boy.
AB  - Cystic lymphangiomas commonly occur in childhood, but breast involvement is an
      extremely rare entity that tends to be more common in adults, with only a few
      cases reported in children. We describe a 6-year-old boy who presented with a
      lump in the left breast that measured 4.5 x 3.5 x 2.5 cm. A local excision was
      performed, and a diagnosis of cystic lymphangioma was confirmed. There was no
      recurrence of the lesion after 18 months after surgical excision. A brief case
      description and review of the relevant literature is presented.

PMID- 19853766
TI  - Modified slide tracheoplasty for congenital tracheal stenosis.
AB  - Slide tracheoplasty has become a standard procedure to treat long-segment
      congenital tracheal stenosis because it is a reasonable and simple technique.
      Slide tracheoplasty does not affect the carina during long-segment congenital
      tracheal stenosis management, and thus lesions of the carina, such as stenosis
      and tracheobronchomalacia can become important causes of extubation failure after
      surgery. In this manusript, we describe the effectiveness of our modified slide
      tracheoplasty, which includes reconstruction of the carina. We have performed
      this technique on three patients, all of whom were extubated without developing
      any respiratory symptoms.

PMID- 19853767
TI  - Ovarian epithelial tumors of low malignant potential: a case series of 5
      adolescent patients.
AB  - Epithelial ovarian neoplasms are uncommon in pediatric and adolescent patients,
      accounting for approximately 20% to 30% of ovarian tumors in adolescent females
      and women younger than 25. Tumors of low malignant potential (LMP) account for a
      significant proportion of epithelial neoplasms in this patient population. This
      case series describes 5 adolescent patients, with a mean age of 14.4 +/- 2.4
      years, diagnosed with ovarian tumors of LMP at one institution. Between November
      2001 and January 2006, 5 patients were diagnosed with ovarian tumors of LMP of
      126 patients who had surgery for adnexal masses. All patients underwent initial
      surgery via laparotomy. Two patients underwent ovarian cystectomy, and 3 had at
      least a unilateral salpingo-oophorectomy. One patient had stage IIIc disease,
      whereas the other 4 patients, not all completely staged, had presumed stage I
      disease. Three patients developed recurrent ovarian masses on follow-up. Two had
      recurrent LMP tumors (one bilateral) and one was a benign mucinous cystadenoma.
      This case series of 5 adolescent patients with ovarian tumors of LMP highlights
      the importance of considering epithelial neoplasms in any pediatric or adolescent
      patient with a pelvic mass and supports conservative management, with staging and
      fertility-sparing surgery; however, appropriate follow-up is essential, as
      evidenced by 3 of 5 patients exhibiting recurrent ovarian masses.

PMID- 19853768
TI  - Intrauterine intussusception: a rare cause of intestinal atresia.
AB  - Intrauterine intussusception is an uncommon cause of intestinal atresia. We
      report a case of ileal atresia owing to antenatal intussusception revealed as an
      intraluminal polypoid lesion after surgical intervention.

PMID- 19853769
TI  - Vascular characterization of clear cell sarcoma of the kidney in a child: a case
      report and review.
AB  - Clear cell sarcoma of the kidney (CCSK) is uncommon pediatric renal tumor and can
      present a significant therapeutic challenge in those patients whose tumors spread
      beyond the kidney. Thus, identifying potential novel targets for treatment may be
      clinically important. Clear cell sarcoma of the kidney is characterized by a
      unique vascular pattern, in which nests of tumor cells are separated by regularly
      spaced, fine fibrovascular septa. This distinctive histopathology raises the
      possibility that understanding the factors which drive angiogenesis in CCSK
      tumors may suggest new therapeutic targets. Here, we describe a case of CCSK and
      present immunohistochemical studies of its vasculature.

PMID- 19853770
TI  - Sonographic evaluation of gastrointestinal obstruction in infants: a pictorial
      essay.
AB  - Traditionally, gastrointestinal contrast studies have been the mainstay of
      evaluating infantile gastrointestinal problems. Because of technological
      advancements, good ultrasonography (USG) machines can provide high-resolution
      images with graphic anatomical clarity, especially in infants and children and
      thus change the traditional diagnostic trends. In this article, we illustrate the
      USG appearances of various causes of gastrointestinal obstruction in infants and
      discuss the role of USG in their evaluation.

PMID- 19853771
TI  - Preoperative imaging of left portal vein at the Rex recess for Rex shunt
      formation using wedged hepatic vein carbon dioxide portography.
AB  - BACKGROUND: In children with extrahepatic portal vein obstruction (EHPVO),
      formation of a mesentericoportal bypass (Rex shunt) restores hepatopetal flow,
      relieves portal hypertension, and reduces variceal bleeding and hypersplenism.
      The Rex shunt is created by inserting a vein graft between the superior
      mesenteric vein and the umbilical segment (Rex) of the left portal vein within
      the Rex recess of the liver. The preoperative evaluation of a patient with EHPVO
      includes an accurate assessment of the venous inflow and outflow. The inflow
      portal vein is readily assessed by ultrasound and magnetic resonance imaging. The
      outflow intrahepatic portal vein is harder to assess. We report our experience of
      patients evaluated with wedged hepatic vein carbon dioxide portography (WHVCP).
      METHOD: All children referred for venography from October 2001 to October 2007
      were prospectively identified, and clinical and radiologic data were reviewed
      retrospectively. The imaging findings were correlated to findings at surgery.
      RESULTS: Eleven children (range, 3-14 years, median, 6 years) were referred for
      preoperative wedged hepatic venography. The left portal vein at the Rex recess
      was clearly identified in 9 patients (82%). In the other 2 patients (18%), the
      Rex segment was not identified despite opacification of left and right
      intrahepatic portal veins; this was taken to indicate an occluded segment. Wedged
      venography was performed with carbon dioxide in 10 patients (91%). Carbon dioxide
      was contraindicated in the final patient because of the presence of a ventricular
      septal defect. CONCLUSION: Our series demonstrates the use of WHVCP as a
      diagnostic tool in preoperative assessment of the Rex segment of left portal vein
      in children with extrahepatic portal vein obstruction.

PMID- 19853772
TI  - Bipolar scissors circumcision is a safe, fast, and bloodless procedure in
      children.
AB  - PURPOSE: The aim of this study is to evaluate bipolar scissors circumcision by
      comparing it with standard freehand scalpel procedure. PATIENTS AND METHODS: Data
      were analyzed from a prospective, randomized study, comparing 2 different
      surgical techniques for pediatric circumcision: the bipolar diathermy scissors
      circumcision technique with those of a conventional scalpel technique. A total of
      230 pediatric patients younger than 16 years (115 in each arm of the trial) who
      were undergoing circumcision were reviewed prospectively. Operative time,
      surgical bleeding, complications, and postoperative morbidity were analyzed.
      Differences between bipolar scissors circumcision and conventional surgery were
      compared. RESULTS: Median blood loss for bipolar circumcision was 0.2 mL (range,
      0-0.8 mL) compared with 2.1 mL in the standard group (range, 0.9-4.2 mL) (P <
      .001). Operative time in the bipolar diathermy treated group was significantly
      decreased compared with conventionally treated patients (10.8 +/- 1.2 vs 19.1 +/-
      2.6 minutes; P < .01). Early and late postoperative morbidity were significantly
      decreased in circumcised patients who underwent the bipolar circumcision
      technique as compared with those who underwent the conventional approach
      regardless of the postoperative edema (22 vs 10; P = .02). CONCLUSIONS: Bipolar
      scissors circumcision approach is an effective and safe procedure alternative to
      the standard scalpel technique in pediatric circumcision with no significant
      morbidity.

PMID- 19853773
TI  - Single-incision multiport laparoscopic orchidopexy: initial report.
AB  - PURPOSE: We report the first use of single-incision multiport access to perform 1
      stage laparoscopic orchidopexy in children without section of the spermatic
      vessels. MATERIAL AND METHODS: Three boys with cryptorchidism were submitted to
      primary laparoscopic 1-stage orchidopexy by using 3 ports (a 10-mm [or 5-mm] port
      placed using open technique and 2 additional 5-mm [or 3-mm] ports) inserted
      through the same periumbilical skin incision with different entrances through the
      abdominal wall. After dissection of the testicular vessels and vas deferens, a 5
      mm port was placed in a tunnel from the scrotum to pull the remnant of the
      gubernaculum down and fix the testicle in a dartos pouch. RESULTS: The mean
      operative time was 83.3 minutes. The estimated blood loss was almost nil, and
      there were no intraoperative complications. CONCLUSION: This approach was
      feasible and safe. However, as with any new technique, its use requires a larger
      number of cases and a longer follow-up to fully evaluate its benefits and
      limitations.

PMID- 19853774
TI  - Pancreatic heterotopia in the skin of the abdominal wall.

PMID- 19853775
TI  - Laparoscopic-percutaneous kidney biopsy in children--a new approach.

PMID- 19853777
TI  - Diagnosis of BD relied in great measure on gallbladder ejection fraction (GBEF)
      after sincalide stimulation on hepatobiliary scintigraphy.

PMID- 19853778
TI  - Report of past meeting 60th annual meeting of the Section on Surgery-American
      Academy of Pediatrics.

PMID- 19853779
TI  - [Renal function as a prognostic marker of mortality in heart failure].

PMID- 19853780
TI  - Annals of Emergency Medicine Journal Club. Journal club: clinical prediction
      rules.
AB  - WHAT IS ALREADY KNOWN ON THIS TOPIC: Previous out-of-hospital studies indicate
      that selective spinal immobilization may miss patients with cervical injury. WHAT
      QUESTION THIS STUDY ADDRESSED: Can paramedics apply the Canadian C-Spine Rule in
      alert, stable, cooperative, blunt-trauma patients to reserve spinal
      immobilization for high-risk patients while avoiding immobilization for low-risk
      patients? WHAT THIS STUDY ADDS TO OUR KNOWLEDGE: In this 1,949-patient cohort,
      paramedics achieved 100% sensitivity and 38% specificity for important cervical
      fractures. HOW THIS MIGHT CHANGE CLINICAL PRACTICE: Use of the Canadian C-spine
      Rule by paramedics may safely avoid unnecessary spinal immobilization.

PMID- 19853781
TI  - Clinical policy: critical issues in the management of adult patients presenting
      to the emergency department with community-acquired pneumonia.
AB  - This clinical policy from the American College of Emergency Physicians focuses on
      critical issues concerning the management of adult patients presenting to the
      emergency department (ED)with community-acquired pneumonia. It is an update of
      the 2001 clinical policy for the management and risk stratification of adult
      patients presenting to the ED with community-acquired pneumonia. A subcommittee
      reviewed the current literature to derive evidence-based recommendations to help
      answer the following questions: (1) Are routine blood cultures indicated in
      patients admitted with community-acquired pneumonia? (2) In adult patients with
      community-acquired pneumonia without severe sepsis, is there a benefit in
      mortality or morbidity from the administration of antibiotics within aspecific
      time course? The evidence was graded and recommendations were given based on the
      strength of evidence.

PMID- 19853783
TI  - Point of the ploughshare.

PMID- 19853784
TI  - Night shift.

PMID- 19853785
TI  - Psychotic woman with painful abdominal distension. Life-threatening psychotropic
      drug-induced gastrointestinal hypomotility.

PMID- 19853786
TI  - Life-threatening cardiac toxicity after chewing inverted nut (pinang-wang).

PMID- 19853787
TI  - Additional information on taser safety.

PMID- 19853789
TI  - Giving and using information: what we know and don't know.

PMID- 19853790
TI  - Prevalence and psychosocial impact of lower urinary tract symptoms in patients
      with Duchenne muscular dystrophy.
AB  - Patients with Duchenne muscular dystrophy (DMD) frequently report lower urinary
      tract symptoms at the outpatient rehabilitation clinic. The purpose of this study
      was to determine the prevalence of lower urinary tract symptoms in the Dutch male
      DMD population and their effect on quality of life. A postal questionnaire was
      sent to members of Dutch DMD patient organisations. 199 male patients with
      confirmed DMD and over the age of 3years were included. 170/199 (85%) patients
      reported one or more lower urinary tract symptoms. Generally, post micturition
      dribble, straining and feeling of incomplete emptying were most frequently
      mentioned. 42% of patients (range 18-76%) experienced the symptoms as a problem.
      In 49/170 (29%) patients, it reduced quality of life. In conclusion, lower
      urinary tract symptoms in DMD patients are under reported and under diagnosed.
      However, the vast majority of male DMD patients with symptoms experience them as
      a problem, often reducing quality of life.

PMID- 19853791
TI  - Chronic alcoholism: insights from neurophysiology.
AB  - INTRODUCTION: Increasing knowledge of the anatomical structures and cellular
      processes underlying psychiatric disorders may help bridge the gap between
      clinical signs and basic physiological processes. Accordingly, considerable
      insight has been gained in recent years into a common psychiatric condition,
      i.e., chronic alcoholism. MATERIAL AND METHODS: We reviewed various physiological
      parameters that are altered in chronic alcoholic patients compared to healthy
      individuals--continuous electroencephalogram, oculomotor measures, cognitive
      event-related potentials and event-related oscillations--to identify links
      between these physiological parameters, altered cognitive processes and specific
      clinical symptoms. RESULTS: Alcoholic patients display: (1) high beta and theta
      power in the resting electroencephalogram, suggesting hyperarousal of their
      central nervous system; (2) abnormalities in smooth pursuit eye movements, in
      saccadic inhibition during antisaccade tasks, and in prepulse inhibition,
      suggesting disturbed attention modulation and abnormal patterns of prefrontal
      activation that may stem from the same prefrontal "inhibitory" cortical
      dysfunction; (3) decreased amplitude for cognitive event-related potentials
      situated along the continuum of information-processing, suggesting that
      alcoholism is associated with neurophysiological deficits at the level of the
      sensory cortex and not only disturbances involving associative cortices and
      limbic structures; and (4) decreased theta, gamma and delta oscillations,
      suggesting cognitive disinhibition at a functional level. DISCUSSION: The
      heterogeneity of alcoholic disorders in terms of symptomatology, course and
      outcome is the result of various pathophysiological processes that physiological
      parameters may help to define. These alterations may be related to precise
      cognitive processes that could be easily monitored neurophysiologically in order
      to create more homogeneous subgroups of alcoholic individuals.

PMID- 19853792
TI  - Autonomic aspect of emotional response in depressed patients: relationships with
      personality.
AB  - STUDY AIM: Affective symptoms are major descriptors of depression; therefore, a
      lot of studies investigated emotional-responsiveness modulation in depression,
      and reported either a potentiation of negative affects, a reduction of positive
      affects, or a reduction of both positive and negative affects. On the other hand,
      personality was classically found to be modulated in depression, with behavioral
      inhibition system (BIS)-related dimensions (namely harm avoidance (HA),
      neuroticism) showing higher scores in depressed subjects. The aim of this study
      was to investigate the relationships between emotional responsiveness (as
      measured by skin conductance response [SCR]) and personality in depression.
      METHODS: SCR was recorded following the presentation of neutral, pleasant, and
      unpleasant pictures in 20 depressed subjects and 20 controls. RESULTS: Pleasant
      pictures elicited more and larger responses than unpleasant ones in control but
      not in depressed subjects. This effect was not modulated by personality.
      Moreover, depressed subjects were found to show generally faster half-recovery
      times and to rate emotional pictures as less arousing than control subjects and
      these effects disappeared when BIS-related dimensions were controlled.
      CONCLUSIONS: These results suggest that BIS-related dimensions are independent
      from the specifically reduced responses to pleasant pictures, but are involved in
      the observed general affect reducing.

PMID- 19853793
TI  - Haemodynamic changes during seizure-like activity in a neonate: a simultaneous AC
      EEG-SPIR and high-resolution DC EEG recording.
AB  - OBJECTIVE: We sought to define the interaction between neonatal epileptic
      discharges and the haemodynamic activities in a control situation (i.e. in the
      absence of cardiorespiratory perturbation or any interaction with normal,
      ongoing, synchronized neuronal activity). METHOD: Alternating-current
      electroencephalography (AC EEG), near-infrared spectroscopy (NIRS), and high
      resolution direct-current (HR DC) EEG were performed in a curarized, ventilated
      neonate with a flat interictal EEG. The seizure-like discharges (SLD) first spike
      was used as a trigger for further averaging of NIRS, AC and DC EEG. Source
      localization was performed on the averaged spike and the averaged, negative DC
      shift. RESULTS: SLD were of maximal amplitude in centroparietal areas and induced
      a change in local haemodynamic parameters characterized by a first increase in
      [HHb] followed by an increase in [HbO(2)] and [HbT]. [HHb] returned to baseline
      at the end of the seizure and decreased thereafter. The negative DC shift started
      before the first spike and the increase in haemodynamic parameters. It then
      became positive and returned to baseline at the end of the seizure. Source
      localization revealed different positions for the first spike and the negative DC
      shift. DISCUSSION: Pure SLD in neonates might induce a negative blood oxygen
      level-dependent (BOLD) effect on the cortex, which occurs after the negative DC
      shift and which has a closer temporal relationship with the neuronal discharge
      than a positive BOLD effect.

PMID- 19853794
TI  - How far do patients with sensory ataxia benefit from so-called "proprioceptive
      rehabilitation"?
AB  - A rehabilitation program including foot sensory stimulation, balance and gait
      training with limited vision was performed in 24 patients with clinically defined
      sensory ataxia. There were 15 patients with bilateral somatosensory loss related
      to chronic neuropathy and nine patients with unilateral loss-related to multiple
      sclerosis. After training, balance control assessed using the Berg Balance Test
      improved similarly in both groups, and Romberg's sign disappeared in some
      patients, suggesting an improvement in dynamic balance and in the proprioceptive
      contribution. Conversely, balance assessed on a static force platform remained
      similar in the open-eyes condition and improved in the closed-eyes condition only
      in patients with unilateral sensory loss. These results show that ataxic patients
      can improve their balance with better results in dynamic conditions and that the
      relative contribution of proprioceptive and visual inputs may depend on the
      extent of somatosensory loss.

PMID- 19853795
TI  - Vestibulocervical reflexes in idiopathic Parkinson disease.
AB  - OBJECTIVES: The mechanism of gait instability in Parkinson disease (PD) is not
      completely understood. We examined the saccular part of the otolith function and
      its possible contribution to gait difficulties in idiopathic PD. METHODS: Fifty
      four PD patients (mean age 66 years, 32 men) were included. These were
      characterized with respect to disease severity, duration, treatment, as well as
      the presence of disease complications, dementia and depression. Vestibular evoked
      myogenic potentials (VEMP) were recorded in patients and 53 healthy controls.
      RESULTS: VEMP responses were recorded in all controls. Unilaterally absent VEMP
      responses were found in 20 (37%) of PD patients and bilaterally absent responses
      in four (7.4%). All patients with preserved peaks had normal latencies as
      compared with controls. The number of PD patients with abnormal/absent VEMP was
      thus significantly higher than in controls (p<0.00). There were no correlations
      between VEMP abnormality and disease stage, falls or medication. A correlation
      was found between abnormal VEMP and depression/antidepressant treatment.
      CONCLUSION: PD patients often have absent vestibulocollic reflexes. Further
      investigations are needed to elucidate the significance of this finding for
      postural stability and gait in this disorder.

PMID- 19853796
TI  - A new case of slow alpha variant during REM sleep.

PMID- 19853799
TI  - Endovascular management of intracranial aneurysms.
AB  - Data from our clinical series and others supports the idea that endovascular coil
      embolization is a reliable form of treatment for both ruptured and unruptured
      cerebral aneurysms. This form of treatment appears from preliminary data to be
      protective against subarachnoid hemorrhage. Although not likely to replace open
      surgery, the continued advancements in technology and supportive clinical data
      will allow endovascular therapy to become a more durable mode of treatment.

PMID- 19853800
TI  - Endovascular treatment of intracranial arteriovenous malformation.
AB  - Arteriovenous malformations (AVMs) of the brain are vascular lesions in which an
      abnormal tangle or nidus of vessels permits pathologic shunting of blood flow
      from the arterial to the venous tree without an intervening capillary bed. With
      brain imaging techniques, an increasing number of AVMs are detected before they
      hemorrhage, leading to new considerations and modifications of interdisciplinary
      management strategies. Treatment options include endovascular embolization,
      microsurgical resection, radiosurgery, medical management, or a combination of
      these. Neuroendovascular therapy is a critical component of this
      multidisciplinary and multimodal approach. The development and introduction of
      newer techniques and agents will continue to affect embolization treatments.

PMID- 19853801
TI  - Neuroendovascular management of acute ischemic stroke.
AB  - Endovascular reperfusion therapy is evolving as a promising treatment in the
      setting of acute ischemic stroke. Careful patient selection and angiographic
      evaluation of the location and extent of occlusion are necessary for the
      successful management of stroke patients. Intra-arterial chemical thrombolysis,
      with such agents as alteplase and urokinase, has shown favorable results in the
      early management of cerebrovascular ischemia. Mechanical thrombolysis is becoming
      an adjunctive or alternative treatment therapy via novel clot dissolution and
      retrieval techniques. Existing and upcoming trials are investigating the safety
      and efficacy of neuroendovascular therapy while attempting to expand its
      indications in acute ischemic stroke.

PMID- 19853802
TI  - Neuroendovascular management of dural arteriovenous malformations.
AB  - Dural arteriovenous fistulas are characterized by abnormal arteriovenous shunting
      localized to the pachymeninges. Fistulae venous drainage is essential to their
      classification, symptomatology, and treatment. Endovascular therapy is rapidly
      progressing to an adjunct or even alternative treatment to microsurgical
      resection. Several techniques, such as transarterial or transvenous embolization
      with metallic coils, NBCA, or Onyx, have been used successfully in several
      studies. The long-term clinical and radiographic outcomes of endovascular therapy
      for the treatment of dural arteriovenous fistulas are satisfactory, and future
      studies are underway for the refinement of these techniques.

PMID- 19853803
TI  - Neuroendovascular management of vasospasm following aneurysmal subarachnoid
      hemorrhage.
AB  - Cerebral vasospasm continues to be the leading treatable cause of death and
      disability in patients with subarachnoid hemorrhage. Transluminal balloon
      angioplasty has been considered a safe and effective treatment for cerebral
      vasospasm resistant to maximal medical treatment. However, it should be performed
      in a timely manner, any delays could potentially increase the risk of hemorrhagic
      infarct. Angioplasty in the affected territory may be of benefit in improving not
      only the angiographic appearance but also the ultimate outcome for the patient,
      if performed in a timely fashion.

PMID- 19853804
TI  - Neuroendovascular management of carotid cavernous fistulae.
AB  - Carotid-cavernous fistulae are abnormal arterial communications within the
      cavernous sinus. Endovascular obliteration is the mainstay therapy for the
      definitive treatment of these lesions. Several approaches have been described.
      These include transarterial or transvenous embolization with balloons, coils,
      particles, or covered stents, and arterial sacrifice. The preferred technique is
      based on the fistula type (direct or indirect), microanatomy, chronicity, and the
      extent of the arterial defect.

PMID- 19853805
TI  - Neuroendovascular management of tumors and vascular malformations of the head and
      neck.
AB  - Endovascular procedures are rapidly expanding as treatment options for
      cerebrovascular diseases and neoplasms of the head and neck and are becoming less
      invasive but more effective. There are potentially dangerous anastomoses between
      the extracranial and intracranial circulations; hence, thorough knowledge of the
      anatomy is essential to minimize the risk of cranial nerve palsies, blindness, or
      neurologic deficits. It is essential to understand the scientific basis of
      treatment rationale based on advancing new neuroimaging techniques to better
      serve patients. An interdisciplinary approach and treatment in high-volume
      centers are vital to obtain maximal benefit for patients.

PMID- 19853806
TI  - Endovascular management of extracranial carotid and vertebral disease.
AB  - Endovascular therapies have become a mainstream option for treatment of many
      extracranial vascular disorders and is the preferred management strategy for
      vascular injury secondary to head and neck malignancy. The interventionalist must
      be familiar with the clinical trials as basis for the management of extracranial
      atherosclerotic disease as well as understanding the therapeutic options, risks,
      and benefits. Nonatherosclerotic injury including trauma, injury due to neoplasm
      or its treatment, and idiopathic lesions have unique considerations important to
      the use and deployment of various devices. The diagnostic approaches, treatment
      strategies, and the role of endovascular techniques in patients with extracranial
      vascular disease are discussed.

PMID- 19853807
TI  - Asymmetric dimethylarginine: understanding the physiology, genetics, and clinical
      relevance of this novel biomarker. Proceedings of the 4th International Symposium
      on ADMA.

PMID- 19853808
TI  - Late myocardial remodeling in cardiac allografts: challenges and opportunities.

PMID- 19853809
TI  - An introduction to the ASPAN evidence-based clinical practice guideline for the
      promotion of perioperative normothermia.

PMID- 19853810
TI  - ASPAN's evidence-based clinical practice guideline for the promotion of
      perioperative normothermia.

PMID- 19853811
TI  - Scope of practice.

PMID- 19853812
TI  - Innovative use of perianesthesia nurses in imaging services: meeting the needs of
      children with disabilities.
AB  - A new imaging center was established within a children's specialty hospital that
      provides services for children and adults with childhood-onset disabilities. New
      services in this advanced imaging center include computed tomography, magnetic
      resonance imaging, fluoroscopy, and ultrasound. Individuals with disabilities are
      particularly at risk for complications during procedures requiring sedation and
      anesthesia. The perianesthesia nurses' role was developed to support the sedation
      needs of this population during imaging services. Perianesthesia nurses developed
      an advanced imaging screening process to prepare patients for sedation during
      imaging services. With these processes, the new Advanced Imaging Center is
      providing timelier and better coordinated imaging services.

PMID- 19853813
TI  - Interventional procedures: best practice to avoid complications.
AB  - Technological advances have allowed treatment of patients using interventional
      radiological imaging including the performance of multiple procedures in almost
      any vessel, eg, angioplasty, stenting, embolization, and coilings. Patients
      undergoing any procedure are at risk for complications because of contrast media,
      radiation exposure, vessel injury, and prolonged time in one position during the
      procedure. Diagnostic-only procedures minimize use of contrast medium and
      radiation time, and generally take about one hour to complete. On the other hand,
      interventional procedures can take several hours and require larger volumes of
      contrast medium and radiation, as well as increased time lying supine on a
      procedure table. This article will discuss several potential and known risks
      associated with interventional procedures, how to monitor for these risks, and
      evidence-based measures to prevent or minimize their occurrence.

PMID- 19853814
TI  - Nurse reports of adverse events during sedation procedures at a pediatric
      hospital.
AB  - The purpose of our study was to examine the reliability of nurse reports of
      adverse events related to procedural sedation in children. A descriptive,
      correlational design was used to analyze for inter-rater agreement between
      prospective adverse event reporting and that identified on independent review of
      the medical record. All sedation documentation at a pediatric hospital over one
      calendar year was reviewed, and inter-rater reliability of reporting was analyzed
      using K statistics. Five thousand forty-five sedation documentation records were
      reviewed. An adverse event rate of 6.52% was identified: 1.92% of adverse events
      were serious, and 4.60% were minor. Although overall agreement between nurse
      reports and independent review was greater than 99%, subanalysis suggested
      greater agreement for serious events than for minor ones (K values: 0.85 vs 0.49,
      P < .01). The results of our study revealed that minor adverse events associated
      with procedural sedation were under-reported, despite clear perianesthesia
      documentation in the medical record that an event had occurred. Improved
      education for perianesthesia nurses regarding the importance of monitoring both
      for serious and minor adverse events will help to identify opportunities to
      improve sedation protocols.

PMID- 19853815
TI  - Effectiveness of the essential oils lavender and ginger in promoting children's
      comfort in a perianesthesia setting.
AB  - This randomized, controlled, blinded study examined the effectiveness of an
      aromatherapy intervention on the reduction of children's distress in a
      perianesthesia setting. The sample included children with and without
      developmental disabilities (n = 94). Subjects in the intervention group received
      an aromatherapy intervention of lavender and ginger essential oils. The control
      group received a placebo intervention of jojoba oil. Distress was measured at two
      times: before induction and in the PACU, using the Faces, Legs, Arms, Cry and
      Consolability (FLACC) scale. The mean distress level was lower for the children
      in the essential oil group, but the effect was not statistically significant (P =
      .055). Parents' responses to survey questions about satisfaction with
      aromatherapy did not differ between groups, although open-ended comments
      indicated a more positive opinion of the benefits of the intervention in the
      aromatherapy group.

PMID- 19853816
TI  - Extubation of pediatric patients: can nurses safely pull the tube?
AB  - The purpose of this study was to evaluate the safety of pediatric extubation
      performed by nurses in the PACU after the implementation of an extubation policy.
      A total of 673 patients were extubated over 12 months. Five-hundred twenty-four
      (77.9%) of these patients met the criteria for nurse extubation; however, only
      304 (58%) were extubated by nurses. One-hundred seventy-nine (34%) patients were
      not extubated by nurses because of a lack of physician order; a physician was
      present for 49 (9.3%) patients, and four (0.8%) patients had complications,
      resulting in a physician extubation. Only 8 (3%) patients extubated by nurses
      developed complications. These results suggest that nurses can safely perform
      endotracheal extubation of the pediatric population.

PMID- 19853817
TI  - Evaluating your information system implementation.

PMID- 19853818
TI  - Perianesthesia practice and the underserved.

PMID- 19853819
TI  - Handoff communication: opportunities for improvement.

PMID- 19853820
TI  - Electronic medical records: the promises and challenges.

PMID- 19853821
TI  - Community grants for research projects.

PMID- 19853822
TI  - Obesity and the perianesthesia patient.

PMID- 19853823
TI  - Advancing your education: just do it!

PMID- 19853824
TI  - Editorial and introduction: new developments in paediatric rheumatic diseases.

PMID- 19853825
TI  - An overview of genetics of paediatric rheumatic diseases.
AB  - The evidence so far suggests that the paediatric inflammatory diseases
      encountered in rheumatology practice may be largely genetic in origin, where
      common single nucleotide polymorphisms (SNPs) in multiple genes contribute to
      risk, with real but variable environmental components. As far as genetic
      susceptibility to common paediatric rheumatic diseases is concerned, only
      juvenile idiopathic arthritis (JIA) has been investigated in any substantial way
      so far. This article discusses susceptibility for different types of JIA, the
      different methods used and their advantages and disadvantages. The genetic code
      is also modifiable by epigenetic mechanisms and examples of these in immunity and
      rheumatoid arthritis are given to indicate another area of research in the
      elucidation of the genetics of paediatric rheumatic diseases.

PMID- 19853826
TI  - Using biology of disease to understand and guide therapy of JIA.
AB  - Juvenile idiopathic arthritis (JIA) is a heterogeneous, multi-factorial disease.
      The ability to distinguish various subtypes of JIA has enabled more directed and
      uniform clinical care. Possible triggers of the disease include genetic and
      environmental factors such as infections and vaccinations. Autoreactive T cells
      responding to unknown antigens are among the mechanisms that perpetuate the cycle
      of autoimmune inflammation once established. There are two groups of candidate
      auto-antigens that are thought to play a role in induction or modulation of T
      cell responses. The first group is derived from cartilage and other joint-related
      tissue and the second group is derived from stress proteins. Several molecules
      have been implicated in the quest to restore immune homeostasis and tolerance,
      such as regulatory T cells, FoxP3, heat shock proteins, cytokines, chemokines and
      other key mediators of inflammation. Treatment strategies might focus on the
      induction of regulation in a more specific fashion.

PMID- 19853827
TI  - Developing outcome measures for paediatric rheumatic diseases.
AB  - This review provides a theoretical background and approach for developing outcome
      measures that are often used to assess the state and course of paediatric
      rheumatic diseases. It describes the important steps in scale development such as
      item generation and reduction, the assessment of scale reliability and various
      forms of validation. The second part of this review described the newly developed
      outcome measures as well as their state of validation. These outcome measures
      include therapeutic response measures, composite disease activity scores for
      juvenile idiopathic arthritis (JIA), global disease activity tools for juvenile
      systemic lupus erythematosus and juvenile dermatomyositis, disease status
      measures in JIA, measures of physical function, measures of health-related
      quality of life, clinical measures of damage and radiographic scoring systems in
      JIA.

PMID- 19853828
TI  - Ensuring that all paediatricians and rheumatologists recognise significant
      rheumatic diseases.
AB  - In many health-care systems around the world, many generalists (defined here as a
      clinician who is not an expert in paediatric musculoskeletal [pMSK] medicine)
      will be the doctor to whom children with MSK problems are most likely to present.
      The generalist is likely to have a clinical background in family medicine and
      paediatrics, but may be a specialist in adult orthopaedics, adult rheumatology or
      emergency care. Therefore, it is critical that the generalist is able to quickly
      recognise a child with significant rheumatic disease in order to initiate the
      proper treatment or referral to a specialist. However, most generalists are ill
      equipped to be able to do so, because of current deficiencies in education and
      training. The aims of this article are as follows:

PMID- 19853829
TI  - Improving the management of paediatric rheumatic diseases globally.
AB  - This article aims to review the various aspects of paediatric rheumatology that
      might be looked on as having a more global emphasis, the advances achieved
      through new technology and communication, the importance of education for both
      the medical community as well as the patient population, the epidemiologic
      variation of diseases and how population migration has brought potential changes
      as well as canvassing some of the considerable new challenges that still need to
      be addressed.

PMID- 19853830
TI  - Systemic JIA: new developments in the understanding of the pathophysiology and
      therapy.
AB  - Systemic juvenile idiopathic arthritis (sJIA) is a rare, systemic inflammatory
      disease classified as a subtype of JIA. Besides arthritis, it is characterised by
      systemic features such as spiking fever, skin rash, hepatosplenomegaly or
      serositis. It is becoming clear now that abnormalities in the innate immunity
      (cytokines such as interleukin (IL)-1, IL-6 and IL-18, and neutrophils and
      monocytes/macrophages rather than lymphocytes) play a major role in the
      pathogenesis of sJIA, distinguishing it from other JIA subtypes. Another
      distinctive feature of sJIA is its strong association with macrophage activation
      syndrome (MAS). Based on this, consensus is emerging that sJIA should be viewed
      as an autoinflammatory syndrome rather than a classic auto-immune disease. As a
      consequence of the progression in understanding the underlying mechanisms of
      sJIA, major changes in the management are evolving. So far, treatment has been
      based on glucocorticosteroids in combination with disease-modifying drugs such as
      methotrexate. Recently, remarkable improvement has been observed with IL-1 and IL
      6 targeted therapies. These therapies might also change the long-term outcome of
      this disease. However, controlled trials set up in international collaboration
      are needed to determine the optimal treatment strategies for all sJIA patients.

PMID- 19853832
TI  - Update in paediatric vasculitis.
AB  - Vasculitis refers to a heterogeneous group of disorders that are characterised by
      inflammatory destruction of blood vessels. Although simple to define, almost
      nothing about vasculitis is simple. From classification to diagnosis, and from
      pathogenesis to management, large gaps remain in our understanding. Despite
      extensive and ongoing research, the fundamental mechanisms underlying the
      initiation and continuation of systemic vasculitis remain poorly understood.
      Thus, vasculitis continues to provide tremendous challenges to both clinicians
      and investigators and remains a rich source of issues for discussion. This review
      concentrates on recent changes proposed for the classification of paediatric
      vasculitis and advances in the concepts of aetiopathogenesis. Availability of
      improved classification criteria for children should prompt planning for
      multicentre-controlled studies for the treatment of these rare but important
      diseases.

PMID- 19853833
TI  - Atypical and incomplete Kawasaki disease.
AB  - Kawasaki disease (KD) is the most common systemic vasculitis in childhood after
      Henoch-Schonlein purpura, and the most common cause of acquired heart disease
      among children living in Western countries. Its diagnosis relies on clinical
      findings; laboratory tests are useful to rule out other causes of unexplained
      fever but are not specific for the diagnosis of KD. Numerous efforts to produce a
      diagnostic algorithm have been made, but without success. Expert opinion is
      therefore required in doubtful cases, especially those that lack classical
      criteria (the so-called atypical or incomplete cases). Renal, gastrointestinal,
      neurologic, pulmonary and ocular involvements have all been described. Infants
      may be at higher risk of complications since recognising manifestations of the
      disease might be more difficult in this group. Approaches to treatment and follow
      up of KD are changing in parallel with changes in concepts of what constitutes
      classical and incomplete KD. Guiding this evolution is the probability that the
      diagnosis is actually KD, the duration of the child's illness and the desired
      effects of therapy. Until a gold standard for diagnosing KD is available, these
      therapeutic decisions will continue to be made on an individual basis.

PMID- 19853834
TI  - What's new in paediatric SLE?
AB  - Although more commonly presenting in adulthood, approximately 15-20% of systemic
      lupus erythematosus (SLE) cases occur before age 16 years. Unfortunately, SLE is
      usually more severe when presenting in childhood, and frequently involves vital
      organs such as the kidney. Over the past several decades, mortality rates have
      dropped, largely due to earlier diagnosis, improved management of the SLE and
      improved general medical care to reduce infection. Treatment strategies for
      nephritis in children is largely adopted from experience in adults, and the
      recent advances in therapeutic options for adults have brought new treatment to
      children. However, determining efficacy is difficult due to the absence of
      clinical trial data. Furthermore, determination of safety in a developing child
      or adolescent cannot be extrapolated from adult studies. As survival has
      improved, numerous secondary complications have emerged, including early
      atherosclerosis. As for adults with SLE, it is generally accepted that
      atherogenesis in SLE results from both disease- and treatment-related factors.
      Most surprising is that persons with childhood-onset SLE can develop myocardial
      ischaemia as early as 20-30 years of age. Better understanding of the
      pathogenesis and development of preventative strategies is needed to ensure that
      these young people do not succumb to atherosclerosis instead of to SLE.

PMID- 19853831
TI  - Juvenile dermatomyositis: new developments in pathogenesis, assessment and
      treatment.
AB  - Juvenile dermatomyositis (JDM) is a rare, potentially life-threatening systemic
      autoimmune disease primarily affecting muscle and skin. Recent advances in the
      recognition, standardised assessment and treatment of JDM have been greatly
      facilitated by large collaborative research networks. Through these networks, a
      number of immunogenetic risk factors have now been defined, as well as a number
      of potential pathways identified in the aetio-pathogenesis of JDM. Myositis
      associated and myositis-specific autoantibodies are helping to sub-phenotype JDM,
      defined by clinical features, outcomes and immunogenetic risk factors. Partially
      validated tools to assess disease activity and damage have assisted in
      standardising outcomes. Aggressive treatment approaches, including multiple
      initial therapies, as well as new drugs and biological therapies for refractory
      disease, offer promise of improved outcomes and less corticosteroid-related
      toxicity.

PMID- 19853835
TI  - [Myasis associated with nasal basal cell carcinoma].

PMID- 19853836
TI  - Script knowledge enhances the development of children's false memories.
AB  - We examined whether script knowledge contributes to the development of children's
      false memories. Sixty 7-year-old and 60 11-year-old children listened to false
      narratives describing either a high-knowledge event (i.e., fingers being caught
      in a mousetrap) or a low-knowledge event (i.e., receiving a rectal enema) that
      were similar in terms of plausibility and pleasantness. Moreover, half of the
      children in each condition received additional suggestive details about the false
      events. Across two interviews, children had to report everything they remembered
      about the events. Script knowledge affected children's false memories in that
      both younger and older children developed more false memories for the high
      knowledge event than for the low-knowledge event. Moreover, at the first
      interview, additional suggestive details inhibited the development of children's
      images into false memories.

PMID- 19853837
TI  - Effectiveness of an ergonomic intervention on work-related posture and low back
      pain in video display terminal operators: a 3 year cross-over trial.
AB  - This study investigated the effectiveness of a workstation ergonomic intervention
      for work-related posture and low back pain (LBP) in Video Display Terminal (VDT)
      workers. 100 VDT workers were selected to receive the ergonomic intervention,
      whereas 100 were assigned to a control group. The two groups were then crossed
      over after 30 months from baseline. Follow-ups were repeated at 5, 12, and 30
      months from baseline and then at 6 months following crossover. OUTCOMES: Work
      related posture and LBP point-prevalence using the Rapid Entire Body Assessment
      method and a Pain Drawing, respectively. The ergonomic intervention at the
      workstation improved work-related posture and was effective in reducing LBP point
      prevalence both in the first study period and after crossover, and these effects
      persisted for at least 30 months. In conclusion, our findings contribute to the
      evidence that individualized ergonomic interventions may be able to improve work
      related posture and reduce LBP for VDT workers.

PMID- 19853838
TI  - Involvement of medullary dorsal horn glial cell activation in mediation of
      masseter mechanical allodynia induced by experimental tooth movement.
AB  - OBJECTIVE: To investigate the involvement of microglial and astrocytic activation
      in the medullary dorsal horn (MDH) during the mediation of masseter area
      allodynia induced by experimental tooth movement (ETM). DESIGN: Five groups of
      adult Sprague-Dawley rats (n=60) were divided into control (CON), minocycline
      (MIN), ETM, and 10mg/kg or 30mg/kg MIN plus ETM (METM) groups. The upper-first
      molar was moved mesially for rats in ETM and METM groups. Rats were pre-injected
      with minocycline in the MIN (30mg/kg) and METM (10mg/kg or 30mg/kg) groups.
      Pressure pain threshold (PPT) in masseter area was tested from day 0 to 14 for
      all 5 groups. Immunohistochemistry against OX42 (microglial marker) or GFAP
      (astrocytic maker) in the MDH was examined at days 1, 3, 7 and 14 for CON, MIN
      and 30mg/kg METM groups. RESULTS: Baseline PPT was expectedly seen in either CON
      or MIN groups, masseter mechanical allodynia was detected in the ETM group from
      day 4 to 13 (P<0.05). OX42 expression level at days 1, 3 and 7, and GFAP
      expression level at days 3, 7 and 14 were higher in ETM (P<0.05), but not in
      30mg/kg METM, than in CON group. Minocycline reduced activation of microglia and
      astrocytes, and significantly attenuated the development of masseter mechanical
      allodynia in this model. CONCLUSIONS: These results indicate that mechanical
      allodynia in the masseter area induced by ETM can be attenuated by minocycline.
      Activation of microglia, possibly together with subsequent activation of
      astrocytes, seems to contribute to masseter mechanical allodynia.

PMID- 19853839
TI  - The ANKK1 gene associated with addictions is expressed in astroglial cells and
      upregulated by apomorphine.
AB  - BACKGROUND: TaqIA, the most widely analyzed genetic polymorphism in addictions,
      has traditionally been considered a gene marker for association with D2 dopamine
      receptor gene (DRD2). TaqIA is located in the coding region of the ANKK1 gene
      that overlaps DRD2 and encodes a predicted kinase ANKK1. The ANKK1 protein
      nonetheless had yet to be identified. This study examined the ANKK1 expression
      pattern as a first step to uncover the biological bases of TaqIA-associated
      phenotypes. METHODS: Northern blot and quantitative reverse-transcriptase
      polymerase chain reaction analyses were performed to analyze the ANKK1 mRNA. To
      study ANKK1 protein expression, we developed two polyclonal antibodies to a
      synthetic peptides contained in the putative Ser/Thr kinase domain. RESULTS: We
      demonstrate that ANKK1 mRNA and protein were expressed in the adult central
      nervous system (CNS) in human and rodents, exclusively in astrocytes. Ankk1 mRNA
      level in mouse astrocyte cultures was upregulated by apomorphine, suggesting a
      potential relationship with the dopaminergic system. Developmental studies in
      mice showed that ANKK1 protein was ubiquitously located in radial glia in the
      CNS, with an mRNA expression pick around embryonic Day 15. This time expression
      pattern coincided with that of the Drd2 mRNA. On induction of differentiation by
      retinoic acid, a sequential expression was found in human neuroblastoma, where
      ANKK1 was expressed first, followed by that of DRD2. An opposite time expression
      pattern was found in rat glioma. CONCLUSIONS: Spatial and temporal regulation of
      the expression of ANKK1 suggest an involvement of astroglial cells in TaqIA
      related neuropsychiatric phenotypes both during development and adult life.

PMID- 19853840
TI  - Determination of deacetylation degree of chitosan: a comparison between
      conductometric titration and CHN elemental analysis.
AB  - Chitosan is a polysaccharide used in a broad range of applications. Many of its
      unique properties come from the presence of amino groups in its structure. A
      proper quantification of these amino groups is very important, in order to
      specify if a given chitosan sample can be used in a particular application. In
      this work, a comparison between the determination of chitosan degree of
      deacetylation by conductometry and CHN elemental analysis was carried out, using
      a rigorous error analysis. Accurate expressions relating CHN composition,
      conductometric titration, and degree of deacetylation, in conjunction with their
      associated errors, were developed and reported in this note. Error analysis
      showed conductometric analysis as an inexpensive and secure method for the
      determination of the degree of deacetylation of chitosan.

PMID- 19853841
TI  - Preparation of a glucan from the roots of Rubus crataegifolius Bge. and its
      immunological activity.
AB  - A water-soluble glucan (RCP-1) was prepared from the roots of Rubus
      crataegifolius Bge. by extraction with hot-water, deproteination by Sevag
      reagent, alpha-amylase treatment and ultrafiltration. RCP-1 consisted of only
      glucose, and its molecular weight was determined to be approximately 7KD by high
      performance gel permeation chromatography (HPGPC). Fourier transform infra-red
      spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), methylation
      and periodate oxidation analyses indicated that RCP-1 was an alpha-d-glucan. Its
      main chains were composed of (1-->4)- and (1-->6)-linked alpha-glucopyranosyls,
      and side chains were single alpha-glucopyranosyl residues attached to the O-6 of
      glucosyls in the main chains. RCP-1 could increase both cytotoxic activity
      against B16 melanoma cells and the production of nitric oxide (NO) of macrophages
      in vitro. Furthermore, in vivo bioassay tests indicated that RCP-1 could
      remarkably enhance T and B lymphocyte proliferations, augment the phagocytosis of
      macrophages and increase the tumour necrosis factor-alpha (TNF-alpha) levels in
      serum.

PMID- 19853842
TI  - Foxn1 is essential for vascularization of the murine thymus anlage.
AB  - We addressed whether vascularization of the thymus anlage depends on Foxn1
      expression. In the thymus anlagen of wild-type mice, CD31(+) endothelial cells
      are initially observed between epithelial cells on embryonic day (Ed)12.5 and
      form luminal structure on Ed13. VEGF are produced in epithelial cells and
      mesenchymal cells which invaginate in the epithelial region of the anlagen on
      Ed13. However, in the nude thymus anlagen, neither CD31(+) cells nor VEGF
      producing mesenchymal cells is detected in the epithelial region. The present
      results indicate that Foxn1 dependent epithelial development is essential for
      vascularization of the thymus anlagen.

PMID- 19853843
TI  - Immune system stimulation in rats by Lactobacillus sp. isolates from Raffia wine
      (Raphia vinifera).
AB  - The immune system consists of organs and several cell types. Antigen interaction
      with these cells induces a cellular immune response mediated by activated cells.
      The effects of lactic acid bacteria on the systemic immune response and on the
      secretory immune system are described. The current investigation sets out to
      examine the possible effects of isolated wine lacto-bacilli upon various
      hematologic and immunologic parameters in rats. We have fed rats with probiotic
      isolates from Raffia wine and challenged with castor oil; two control groups were
      fed with castor oil and others were not. We counted blood cells at the end of the
      experiment; all isolates seemed to cause a decrease of circulating white blood
      cells. The percentage of lymphocytes and the total protein in the spleen
      increased in the treated animals; also a normal aspect of faeces was observed
      compared to the control. These isolates of Lactobacillus seem to occur to immune
      cell-mediated responses in rats.

PMID- 19853844
TI  - [Introduction and operation of a multiple trauma unit in a general hospital].
AB  - INTRODUCTION: Although there is ample evidence on the importance of having good
      protocols for Trauma patient care, a teaching system for the personnel involved
      in this care is needed. METHODS: The aim is to describe how we have organised the
      care for this type of patient in Torrevieja Hospital by creating a Trauma Surgery
      Unit, a Trauma Committee and a Trauma Team. We also describe how we have
      developed training in order to ensure personnel get the knowledge and skills to
      care for these patients correctly (Trauma Surgery Course). RESULTS: We
      prospectively describe the results. Seventy-nine patients were attended to and
      38% had sustained combined multiple injuries, 35% isolated thoracic trauma, 15%
      combined thorax and abdomen, and 12% abdomen. The most frequent cause of trauma
      was traffic accident, closely followed by stab wounds. Trauma team activation was
      made in 27 cases. Overall mortality rate was 8.8%. During this period of time, 5
      editions of the course have been given and 29.5% of the target personnel have
      already participated in them. CONCLUSIONS: We conclude by highlighting the
      importance of having adequate protocols for treating these patients and the
      correct means for teaching the personnel.

PMID- 19853845
TI  - A purple giraffe is faster than a purple elephant: inconsistent phonology affects
      determiner selection in English.
AB  - The form of a determiner is dependent on different contextual factors: in some
      languages grammatical number and grammatical gender determine the choice of a
      determiner variant. In other languages, the phonological onset of the element
      immediately following the determiner affects selection, too. Previous work has
      shown that the activation of opposing determiner forms by a noun's grammatical
      properties leads to slower naming latencies in a picture naming task, as does the
      activation of opposing forms by the interaction between a noun's gender and the
      phonological context. The present paper addresses the question of whether
      phonological context alone is sufficient to evoke competition between determiner
      forms. Participants produced English phrases in which a noun phrase's phonology
      required a determiner that was the same as or differed from the determiner
      required by the noun itself (e.g., apurple giraffe; an orange giraffe). Naming
      latencies were slower when the phrase-initial determiner differed from the
      determiner required by the noun in isolation than when the phrase-initial
      determiner matched the isolated-noun determiner. This was true both for definite
      and indefinite determiners. The data show that during the production of a
      determiner-noun phrase, nouns automatically activate the phonological forms of
      their determiners, which can compete with the phonological forms that are
      generated by an assimilation rule.

PMID- 19853846
TI  - Automated classification of cells in sub-epithelial connective tissue of oral sub
      mucous fibrosis-an SVM based approach.
AB  - Quantitative evaluation of histopathological features is not only vital for
      precise characterization of any precancerous condition but also crucial in
      developing automated computer aided diagnostic system. In this study segmentation
      and classification of sub-epithelial connective tissue (SECT) cells except
      endothelial cells in oral mucosa of normal and OSF conditions has been reported.
      Segmentation has been carried out using multi-level thresholding and subsequently
      the cell population has been classified using support vector machine (SVM) based
      classifier. Moreover, the geometric features used here have been observed to be
      statistically significant, which enhance the statistical learning potential and
      classification accuracy of the classifier. Automated classification of SECT cells
      characterizes this precancerous condition very precisely in a quantitative manner
      and unveils the opportunity to understand OSF related changes in cell population
      having definite geometric properties. The paper presents an automated
      classification method for understanding the deviation of normal structural
      profile of oral mucosa during precancerous changes.

PMID- 19853847
TI  - A computationally advantageous system for fitting probabilistic decompression
      models to empirical data.
AB  - To investigate the nature and mechanisms of decompression sickness (DCS), we
      developed a system for evaluating the success of decompression models in
      predicting DCS probability from empirical data. Model parameters were estimated
      using maximum likelihood techniques. Exact integrals of risk functions and tissue
      kinetics transition times were derived. Agreement with previously published
      results was excellent including: (a) maximum likelihood values within one log
      likelihood unit of previous results and improvements by re-optimization; (b) mean
      predicted DCS incidents within 1.4% of observed DCS; and (c) time of DCS
      occurrence prediction. Alternative optimization and homogeneous parallel
      processing techniques yielded faster model optimization times.

PMID- 19853848
TI  - Cognitive and affective disturbances following focal cerebellar damage in adults:
      a neuropsychological and SPECT study.
AB  - The traditional view on cerebellar functioning has recently been challenged by
      results from neuroanatomical, neuroimaging and clinical studies. In this
      contribution, eighteen patients with primary cerebellar lesions (vascular: n=13;
      neoplastic: n=5) were systematically investigated by means of an extensive
      neuropsychological test battery. Fifteen patients (83%) presented with a broad
      variety of cognitive and linguistic deficits following cerebellar damage.
      Disturbances of attention (72%), executive functioning (50%) and memory (50%)
      were most commonly found. Analyses of our results tend to support the hypothesis
      of a lateralization of cognitive modulation within the cerebellum, the right
      cerebellar hemisphere being associated with logical reasoning and language
      processing and the left cerebellum mediating right-hemispheric functions
      including attentional and visuo-spatial skills. In addition, nine patients (50%)
      presented with frontal-like behavioural and affective alterations. In an attempt
      to determine the working-mechanism underlying cerebellar-induced cognitive and
      affective disturbances, all patients were investigated by means of quantified Tc
      99m-ethylenecysteine dimer (ECD) single photon emission computerized tomography
      (SPECT) studies. From a semiological point of view, damage to the cerebellum can
      cause a broad spectrum of clinically significant cognitive and affective
      disturbances. From a pathophysiological point of view, quantified SPECT data,
      reflecting the phenomenon of cerebello-cerebral diaschisis, support the
      functional impact of the cerebellar lesion on cortical functioning through
      disruption of cerebello-cerebral connections.

PMID- 19853849
TI  - Is the visual analyzer orthographic-specific? Reading words and numbers in letter
      position dyslexia.
AB  - Letter position dyslexia (LPD) is a deficit in the encoding of letter position
      within words. It is characterized by errors of letter migration within words,
      such as reading trail as trial and form as from. In order to examine whether LPD
      is domain-specific, and to assess the domain-specificity of the visual analysis
      system, this study explored whether LPD extends to number reading, by testing
      whether individuals who have letter migrations in word reading also show
      migrations while reading numbers. The reading of words and numbers of 12 Hebrew
      speaking individuals with developmental LPD was assessed. Experiment 1 tested
      reading aloud of words and numbers, and Experiment 2 tested same-different
      decisions in words and numbers. The findings indicated that whereas the
      participants with developmental LPD showed a large number of migration errors in
      reading words, 10 of them read numbers well, without migration errors, and not
      differently from the control participants. A closer inspection of the pattern of
      errors in words and numbers of two individuals who had migrations in both numbers
      and words showed qualitative differences in the characteristics of migration
      errors in the two types of stimuli. In word reading, migration errors appeared
      predominantly in middle letters, whereas the errors in numbers occurred mainly in
      final (rightmost) digits. Migrations in numbers occurred almost exclusively in
      adjacent digits, but in words migrations occurred both in adjacent and in
      nonadjacent letters. The results thus indicate that words can be selectively
      impaired, without a parallel impairment in numbers, and that even when numbers
      are also impaired they show different error pattern. Thus, the visual analyzer is
      actually an orthographic visual analyzer, a module that is domain-specific for
      the analysis of words.

PMID- 19853851
TI  - Robust model predictive control design with input constraints.
AB  - The paper addresses the problem of designing a robust output/state model
      predictive control for linear polytopic systems with input constraints. The new
      predictive and control horizon model is derived as a linear polytopic system.
      Lyapunov function approach guarantees the quadratic stability and guaranteed cost
      for closed-loop system. The invariant set and an algorithm approach similar to
      Soft Variable-Structure Control (SVSC), ensures input constraints for the model
      predictive plant control system. In the proposed control scheme, the required on
      line computation load is significantly less than in MPC literature, which opens
      the possibility to use these control design schemes not only for plants with slow
      dynamics, but also for faster ones.

PMID- 19853850
TI  - The relative cost of bent-hip bent-knee walking is reduced in water.
AB  - The debate about how early hominids walked may be characterised as two competing
      hypotheses: They moved with a fully upright (FU) gait, like modern humans, or
      with a bent-hip, bent-knee (BK) gait, like apes. Both have assumed that this
      bipedalism was almost exclusively on land, in trees or a combination of the two.
      Recent findings favoured the FU hypothesis by showing that the BK gait is 50-60%
      more energetically costly than a FU human gait on land. We confirm these findings
      but show that in water this cost differential is markedly reduced, especially in
      deeper water, at slower speeds and with greater knee flexion. These data suggest
      that the controversy about australopithecine locomotion may be eased if it is
      assumed that wading was a component of their locomotor repertoire and supports
      the idea that shallow water might have been an environment favourable to the
      evolution of early forms of "non-optimal" hominid bipedalism.

PMID- 19853852
TI  - Early diagnosis of compartment syndrome: continuous pressure measurement or not?

PMID- 19853853
TI  - Capillary electrophoretic study of thiolated alpha-cyclodextrin-capped gold
      nanoparticles with tetraalkylammonium ions.
AB  - Capillary zone electrophoresis (CZE) has been employed to characterize nanometer
      sized thiolated alpha-cyclodextrin-capped gold nanoparticles (alpha-CD-S-AuNPs).
      The addition of tetrabutylammonium (Bu(4)N(+)) ions to the run buffer greatly
      narrows the migration peak of alpha-CD-S-AuNP. The optimal run buffer was
      determined to be 10mM Bu(4)N(+) in 30 mM phosphate buffer at pH 12 and an applied
      voltage of 15 kV. The effect of various tetraalkylammonium ions on the peak width
      and electrophoretic mobility (mu(e)) of alpha-CD-S-AuNP was studied in detail.
      Bu(4)N(+) ions assist in inter-linking the alpha-CD-S-AuNPs and narrowing the
      migration peak in CZE. This observation can be explained by the fact that each
      Bu(4)N(+) ion can simultaneously interact with several hydrophobic cavities of
      the surface-attached alpha-CDs on AuNPs. The TEM images show that alpha-CD-S
      AuNPs with Bu(4)N(+) are linked together but in the absence of Bu(4)N(+), they
      are more dispersed. The migration mechanism in CZE is based on the formation of
      inclusion complexes between Bu(4)N(+) and alpha-CD-S-AuNPs which induces changes
      in the charge-to-size ratio of alpha-CD-S-AuNPs and mu(e). An inverse linear
      relationship (r(2)>0.998) exists between the mu(e) and size of alpha-CD-S-AuNPs
      in the core range 1.4-4.1 nm. The CZE analyses are rapid with migration time less
      than 4 min. A few nanoliters of each of the alpha-CD-S-AuNP samples were injected
      hydrodynamically at 0.5 psi for 5s. Our work confirms that CZE is an efficient
      tool for characterizing the sizes of alpha-CD-S-AuNPs using Bu(4)N(+) ions.

PMID- 19853854
TI  - Development of a versatile, easy and rapid atmospheric monitor for benzene,
      toluene, ethylbenzene and xylenes determination in air.
AB  - A new procedure for the passive sampling in air of benzene, toluene, ethylbenzene
      and xylene isomers (BTEX) is proposed. A low-density polyethylene layflat tube
      filled with a mixture of solid phases provided a high versatility tool for the
      sampling of volatile compounds from air. Several solid phases were assayed in
      order to increase the BTEX absorption in the sampler and a mixture of florisil
      and activated carbon provided the best results. Direct head-space-gas
      chromatography-mass spectrometry (HS-GC-MS) measurement of the whole deployed
      sampler was employed for a fast determination of BTEX. Absorption isotherms were
      used to develop simple mathematical models for the estimation of BTEX time
      weighted average concentrations in air. The proposed samplers were used to
      determine BTEX in indoor air environments and results were compared with those
      found using two reference methodologies: triolein-containing semipermeable
      membrane devices (SPMDs) and diffusive Radiello samplers. In short, the developed
      sampling system and analytical strategy provides a versatile, easy and rapid
      atmospheric monitor (VERAM).

PMID- 19853855
TI  - Characterizing the Memory Effect on the amylose tris(3,5-dimethylphenyl)
      carbamate stationary phase.
AB  - Acid/base modifiers are sometimes used as additives in normal phase elution on
      columns packed with CHIRALPAK AD. They affect enantioseparations in ways that are
      not understood for the lack of systematic studies, which makes the scale-up of
      preparative separations difficult to predict. Once a column has been exposed to
      these modifiers, the selectivity of certain pairs of enantiomers may change, for
      the better or the worse. Numerous molecules that are affected by this phenomenon
      are listed in the literature. We selected five of them, the selectivity of which
      changes as more acidic or basic solutions are percolated through the column. The
      selectivity of ketoprofen, 4-chlorophenylalanine methyl and ethyl esters improves
      as a solution of Ethanesulfonic Acid is percolated through the column. The
      selectivity of Propranolol HCl and Troger's base increases as a solution of
      diisopropylamine is percolated through the column. Each one of these five
      compounds is inversely affected by the percolation of the opposite acid/base
      solution. We used trans-Stilbene Oxide (tso) as a "standard" to determine the
      columns stability because no Memory Effect is observed for it (its retention,
      enantioselectivity, and resolution remain constant). Karl Fisher titrations
      showed that only slight changes in the water content of the mobile phase
      occurred, and that a unique water to polymer moiety ratio is important.
      Analytical studies of the stationary phase suggest that slow
      protonation/deprotonation of water attached to the carbamate moiety may be
      responsible for the acid/base Memory Effect. Finally, we showed that the Memory
      Effect can be minimized by percolating through the column a sufficiently
      concentrated solution of the appropriate acid or base. Thus, columns that were
      unreliable for method development, due to the Memory Effect, can now be used. As
      a result, the need to store several CHIRALPAK AD columns, specific for each
      condition of the Memory Effect, is eliminated.

PMID- 19853856
TI  - Microscale solid phase extraction of glyphosate and aminomethylphosphonic acid in
      water and guava fruit extract using alumina-coated iron oxide nanoparticles
      followed by capillary electrophoresis and electrochemiluminescence detection.
AB  - A microscale solid-phase extraction (SPE) method using alumina-coated iron oxide
      nanoparticles (Fe(3)O(4)@Al(2)O(3) NPs) as the affinity adsorbent for glyphosate
      (GLY) and its major metabolite aminomethylphosphonic acid (AMPA) in aqueous
      solution is reported. One milligram of Fe(3)O(4)@Al(2)O(3) NPs was employed to
      extract both analytes in 5 ml of aqueous solution. After 5 min extraction,
      magnetic NPs were isolated from sample solution by employing an external magnet.
      Followed by rinsing the NPs with 5 microl of 20 mM Na(4)P(2)O(7) solution for 5
      min, the extract was directly analyzed using the derivatization-free CE
      electrochemiluminescence (CE-ECL) method. With a sample-to-extract volume ratio
      of 1000, the enrichment factors for GLY and AMPA were 460 and 64, respectively.
      The limits of detection (LODs) were 0.3 and 30 ng ml(-1) for GLY and AMPA in
      water, respectively. The developed method was applied to the analysis of GLY in
      guava fruit. The LOD of GLY in guava was 0.01 microg g(-1). Total analysis time
      including sample pretreatment, SPE and CE-ECL was less than 1h.

PMID- 19853857
TI  - Catechol derivatives-coated Fe3O4 and gamma-Fe2O3 nanoparticles as potential MRI
      contrast agents.
AB  - Superparamagnetic iron oxide nanoparticles, Fe(3)O(4) and gamma-Fe(2)O(3), were
      produced by the so-called polyol process. In order to stabilize the particles in
      a physiological environment as potential contrast agents for Magnetic Resonance
      Imaging (MRI), the as-prepared particles were successfully transferred to an
      aqueous medium through ligand exchange chemistry of the adsorbed polyol species
      with the dopamine or the catechaldehyde. The ligands were able to participate in
      bidentate binding to the nanoparticles surface and to improve the stability of
      aqueous suspensions of the nanoparticles. Analysis was performed by various
      techniques including X-ray diffraction, transmission electron microscopy,
      infrared spectroscopy and thermal analysis. The results of magnetic measurements
      and initial in vitro magnetic resonance imaging essays are presented for the pre-
      and post-surface modified nanoparticles, respectively and discussed in relation
      with their structure and microstructure.

PMID- 19853858
TI  - Droplets wetting on filament rails: surface energy and morphology transition.
AB  - The morphology of liquid droplets wetting on filaments depends on the filament
      configuration, droplet volume, and contact angle. A stable morphology is the one
      that minimizes the potential energy of the droplet-filament system, while
      morphology transition may happen when an intermediate state exists which
      corresponds to a higher potential energy. This paper aims to explore such
      morphology transition of droplet wetting on filament rails made of two parallel
      identical microfilaments. Detailed numerical simulations were performed to
      extract the surface energy of the droplet-filament system at varying filament
      spacings, droplet volumes, and contact angles. Critical conditions of the
      morphology transition between two symmetrical wetting morphologies (i.e., liquid
      droplet bridge and barrel-shaped droplet) were determined. A family of
      characteristic curves in terms of the dimensionless droplet volume vs the
      filament spacing at varying contact angles was obtained, which can be used as a
      universal law to govern the morphology transition for such droplet-filament rail
      systems. The results and concepts presented in this work can be extended to broad
      wetting systems and utilized for the analysis and design of microfluidic devices
      and testers based on droplet-filament systems.

PMID- 19853859
TI  - Effect of alkyl chain asymmetry on catanionic mixtures of hydrogenated and
      fluorinated surfactants.
AB  - In this work we studied and compared the physicochemical properties of the
      catanionic mixtures cetyltrimethyl-ammonium bromide-sodium dodecanoate,
      cetyltrimethyl-ammonium bromide-sodium perfluorodacanoate, octyltrimethylammonium
      bromide-sodium perfluorodacanoate and cetyltrimethyl-ammonium bromide-sodium
      octanoate by a combination of rheological, transmission electron microscopy (TEM)
      and polarized optical microscopy measurements. The binary mixtures of the
      surfactants have been analyzed at different mixed ratios and total concentration
      of the mixture. Mixtures containing a perfluorinated surfactant are able to form
      lamellar liquid crystals and stable spontaneous vesicles. Meanwhile, system
      containing just hydrogenated surfactants form hexagonal phases or they are
      arranged in elongated aggregates.

PMID- 19853860
TI  - Aortic intima media thickness is an early marker of atherosclerosis in children
      with type 1 diabetes mellitus.
AB  - OBJECTIVE: To compare aortic intima media thickness (aIMT) to carotid intima
      media thickness (cIMT) as a marker of early atherosclerosis in children with type
      1 diabetes mellitus and to examine the associations of aIMT to known
      cardiovascular risk factors. STUDY DESIGN: 66 children with type 1 diabetes
      mellitus (age, 14.1 +/- 2.5 years; 37 male) and 32 healthy control subjects (age,
      14.2 +/- 3 years; 15 male) underwent assessment of vascular structure (cIMT and
      aIMT) and vascular function (flow mediated dilatation [FMD] and glyceryl
      trinitrate induced dilatation [GTN]). Fasting blood tests were taken to measure
      levels of hemoglobin A1c, high sensitive C reactive protein, total
      homocyst(e)ine, serum folate, red cell folate, and lipids. RESULTS: aIMT, but not
      cIMT, was significantly greater in the children with type 1 diabetes mellitus
      than in control subjects (P < .001). In children with type 1 diabetes mellitus,
      aIMT correlated with glycosylated hemoglobin (r = 0.31, P = .01) and was
      independently associated with age (beta = 0.38, P = .001) and low-density
      lipoprotein cholesterol level (beta = 0.38, P = .001). Vascular function (GTN)
      was worse in children with type 1 diabetes mellitus who had an aIMT >95th
      percentile, as defined with the control subjects. CONCLUSIONS: aIMT is an earlier
      marker than cIMT of preclinical atherosclerosis in children with type 1 diabetes
      mellitus and relates to known cardiovascular risk factors and metabolic control.

PMID- 19853861
TI  - Reversible acute leukoencephalopathy as a form of presentation in cerebral
      amyloid angiopathy.
AB  - BACKGROUND: Cerebral amyloid angiopathy (CAA) may present as cerebral
      haemorrhage, cerebral infarction and periventricular white matter lesions.
      Reversible leukoencephalopathy is a rare manifestation of CAA. AIMS OF THE STUDY:
      To describe two patients with reversible acute leukoencephalopathy as the first
      manifestation of CAA. PATIENTS: Two consecutive patients were admitted to our
      neurology department with transient focal neurological symptoms. They showed
      reversible focal leukoencephalopathy on magnetic resonance imaging (MRI). CAA was
      finally diagnosed in both, and pathologically confirmed in one. The latter
      patient showed multiple foci of petechial bleeding in the cortex and subcortex in
      T2-weighted GRE sequences, suggestive of CAA. CONCLUSION: Reversible acute focal
      leukoencephalopathy may be an infrequent clinical and radiological pattern of
      CAA.

PMID- 19853862
TI  - Relation of baseline presence and severity of renal disease to long-term
      mortality in persons with known stroke.
AB  - BACKGROUND: Little is known about the long-term prognostic impact of baseline
      chronic kidney disease (CKD) on outcomes after stroke. We assessed the
      association of diagnosis and severity of baseline CKD with risk of mortality
      among persons with a history of stroke. METHODS: Data from the National Health
      and Nutrition Examination Survey (NHANES) a nationally representative sample of
      US adults were analyzed. The study population consisted of 425 individuals aged >
      or =55 years with a baseline history of stroke followed-up from NHANES III survey
      participation (1988-1994) through mortality assessment in 2000. CKD outcomes were
      glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) and urinary albumin to
      creatinine ratio (UACR) >30 mg/g of creatinine. CKD severity was categorized per
      national guidelines. Proportional hazard regression (Cox) was utilized to explore
      the independent relationship between CKD vs. all-cause and cardiovascular
      mortality after adjusting for confounders. RESULTS: Among the cohort, 55.8% were
      female, 77.3% aged > or =65 years. Baseline serum creatinine was higher among
      persons with known stroke who later died vs. remained alive (p<0.01).
      Multivariable models showed that persons with low GFR (HR, 1.87 95% CI=1.30
      2.68), CKD stages 1-2 (HR 1.84; 95% CI=1.06-3.20), 3 (HR 2.58; 95% CI=1.54-4.32),
      and 4-5 (HR 5.93; 95% CI=2.31-5.20) but not elevated UACR, had an independently
      higher relative hazard of death compared to individuals without these conditions.
      Similar results were seen with cardiovascular-specific mortality. CONCLUSIONS:
      Baseline CKD, even of mild severity, is an independent predictor of future
      mortality among persons with known stroke.

PMID- 19853863
TI  - Complex diaphragm reconstruction using dermal collagen matrix after multivisceral
      resection of retroperitoneal sarcoma.

PMID- 19853864
TI  - Survival of patients on dialysis having off-pump versus on-pump coronary artery
      bypass surgery in the United States.
AB  - BACKGROUND: Patients on dialysis sustain at least a threefold higher in-hospital
      mortality rate and markedly higher long-term mortality following coronary artery
      bypass graft surgery than the general population. Smaller studies have suggested
      that dialysis patients have superior outcomes with off-pump compared with on-pump
      coronary artery bypass surgery. METHODS: From the United States Renal Data System
      database, 13,085 patients on dialysis having first coronary artery bypass surgery
      between 2001 and 2006 were identified. Of these, 2335 (17.8%) had off-pump
      coronary artery bypass surgery. The Kaplan-Meier method was used to estimate
      survival of patients having off-pump coronary artery bypass and patients having
      on-pump coronary artery bypass. A Cox proportional hazards model was used to
      assess effects of off-pump coronary artery bypass on mortality with adjustment
      for baseline patient characteristics. RESULTS: Off-pump coronary artery bypass
      surgery was associated with significantly reduced all-cause mortality compared
      with on-pump coronary artery bypass surgery (hazard ratio 0.92, 95% confidence
      interval 0.86-0.99, P = .02). The observed survival benefit was most notable in
      the first year after surgery (70.3% vs 68.7%) and was lost 2 years after surgery
      (55.4% vs 55.2%). No difference was noted in the in-hospital mortality rate with
      off-pump coronary artery bypass surgery versus on-pump coronary artery bypass
      surgery (9.7% vs 11.0%, P = .06). Cardiac mortality during the follow-up period
      was similar (23.6% vs 23.8%; adjusted hazard ratio 0.95, 95% confidence interval
      0.86-1.04, P = .26). Use of internal thoracic grafts was independently associated
      with improved survival after coronary artery bypass surgery (hazard ratio, 0.92;
      95% confidence interval, 0.87-0.98, P = .0057). CONCLUSIONS: Patients on dialysis
      sustain high in-hospital and 2-year mortality rates after coronary artery bypass
      surgery. Off-pump coronary artery bypass is associated with modestly increased
      survival compared with on-pump coronary artery bypass, a benefit most marked
      early after off-pump coronary artery bypass.

PMID- 19853865
TI  - Ibuprofen for neuroprotection after cerebral ischemia.
AB  - OBJECTIVE: Ibuprofen has been shown to reduce cerebral ischemic injury, such as
      may occur after deep hypothermic circulatory arrest. We investigated whether
      ibuprofen has direct protective effects against excitotoxic neuronal injury, as
      may be seen after cerebral ischemia, by using a cell culture model. METHODS:
      Mixed cortical cultures containing neuronal and glial cells were prepared from
      fetal mice at 13 to 15 days gestation, plated on a layer of confluent astrocytes
      from 1- to 3-day-old postnatal pups. Near-pure neuronal cultures containing less
      than 5% astrocytes were obtained from mice of the same gestational stage. Slowly
      triggered excitotoxic injury was induced at 37 degrees C by 24-hour exposure to
      12.5 micromol/L N-methyl-D-aspartate or 50 micromol/L kainate. Neuronal death was
      quantified by release of lactate dehydrogenase from damaged cells. Data were
      analyzed using 1-way analysis of variance with Tukey post hoc multiple
      comparisons. RESULTS: In mixed cultures, ibuprofen concentrations of 25
      microg/mL, 50 microg/mL, and 100 microg/mL all significantly reduced N-methyl-D
      aspartate-induced neuronal cell death from 74.5% to 56.1%, 38.7%, and 12.3%,
      respectively, revealing a strong dose response (P < .001). In near-pure cultures,
      ibuprofen at a concentration of 25 microg/mL failed to protect neurons,
      indicating that the neuroprotective effects of ibuprofen require interaction with
      glial cells. Furthermore, ibuprofen at 100 microg/mL was not protective against
      neuronal cell death induced by kainate excitotoxicity in near-pure culture but
      was effective in mixed cultures. CONCLUSION: Ibuprofen provides neuroprotection
      through glial cells against excitotoxic neuronal injury caused by glutamatergic
      excitotoxicity after cerebral ischemia as demonstrated by reduced neuronal cell
      death in mixed cell cultures. Further studies are needed to evaluate the
      potential of ibuprofen to reduce neurologic injury in patients experiencing an
      hypoxic/ischemic insult.

PMID- 19853866
TI  - Excision of atrial myxoma using robotic technology.
AB  - OBJECTIVE: This study is to discuss a surgical approach for ideal and safe
      resection of atrial myxoma using the da Vinci S Surgical System (Intuitive
      Surgical, Inc, Sunnyvale, Calif). METHODS: Nineteen consecutive patients
      underwent resection of atrial myxomas with the da Vinci S Surgical System. Mean
      age of the patients was 46 +/- 16 years. Mean tumor size was 45 x 5.5 cm. Fifteen
      tumors were in the left atrium, of which 11 tumors arose from the interatrial
      septum, 2 from the posterocaudal wall, 1 from the root of the anterior leaflet of
      the mitral valve, and 1 from the left atrial roof. In 13 patients, exploration
      was conducted through a left atriotomy anterior to the pulmonary veins and
      excision was achieved by dissecting a plane through the atrial muscle at the
      point of attachment. In the first 2 patients, exploration and excision were
      conducted through an oblique right atriotomy. Four tumors were in right atrium,
      all of which were resected from the beating heart. The da Vinci instrument arms
      were inserted through three 1-cm trocar incisions in the right side of the chest.
      Via 4 port incisions and a 1.5-cm working port, all the procedures were completed
      with a 30 degrees angled endoscope facing upward with the da Vinci S robot.
      RESULTS: Resection was successful in all patients. There were no operative
      deaths, strokes, or other complications. All the patients were discharged. No
      recurrences of tumor or septal leakage were found in the complete 1- to 18-month
      follow-up. CONCLUSIONS: The excision of atrial myxomas with the da Vinci S
      Surgical System is feasible, efficacious, and safe. Surgical results are
      excellent.

PMID- 19853867
TI  - The unidirectional valve patch provides no benefits to early and long-term
      survival in patients with ventricular septal defect and severe pulmonary artery
      hypertension.
AB  - OBJECTIVE: Our aim was to test whether a unidirectional valve patch would provide
      benefit to early and long-term survival for patients with ventricular septal
      defect and severe pulmonary artery hypertension. METHODS: Eight hundred seventy
      six cases of ventricular septal defect with severe pulmonary artery hypertension
      were closed with or without a unidirectional valve patch and were classified as
      the unidirectional valve patch (UVP) group (n = 195) and nonvalve patch (NVP)
      group (n = 681), respectively. Propensity scores of inclusion into the UVP group
      were used to match 138 pairs between the 2 groups. Kaplan-Meier survival curves
      were constructed to compare early and long-term survival. RESULTS: For the 138
      propensity-matched pairs, there were 7 and 9 early deaths (in-hospital deaths) in
      the UVP and NVP groups, respectively. The difference in early mortality between
      the 2 groups did not reach statistical significance (chi(2) = 0.265, P = .6064).
      With a mean of 9.2 +/- 4.92 years' and 2511 patient-years' follow-up, there were
      6 late deaths in the UVP group and 7 late deaths in the NVP group. The difference
      in actuarial survival at 5, 10, 15, and 18 years between the 2 groups was not
      significant (log-rank test, chi(2) = 0.565, P = .331). The difference in the late
      mortality between the groups with or without a patent patch at the time of
      discharge did not reach statistical significance (chi(2) = 1.140, P = .2856).
      There was no difference between the 2 groups in the 6-minute walk distance
      assessed at the last follow-up (525.9 +/- 88.0 meters for the UVP group and 536.5
      +/- 95.8 meters for the NVP group, F = 1.550, P = .214). CONCLUSION: A
      unidirectional valve patch provides no benefits to early and long-term survival
      when it is used to deal with ventricular septal defect and severe pulmonary
      artery hypertension.

PMID- 19853868
TI  - Mediastinoscopy-assisted minimally invasive closure of a bronchopleural fistula:
      a new technique to manage an old problem.

PMID- 19853869
TI  - Sex- and ethnic group-specific nationwide trends in the use of coronary artery
      bypass grafting in the United States.
AB  - OBJECTIVE: This study examined nationwide trends in use of coronary artery bypass
      grafting between 1988 and 2004. METHODS: The Nationwide Inpatient Sample database
      was used to calculate age-adjusted rate of coronary artery bypass grafting from
      1988 to 2004. Specific International Classification of Diseases, Ninth Revision,
      Clinical Modification codes for coronary artery bypass grafting were used to
      compile data. Patient demographic data were also analyzed. RESULTS: The database
      recorded 1,145,285 patients older than 40 years who underwent coronary artery
      bypass grafting from 1988 to 2004. Mean age was 60.21 +/- 10.55 years. Male
      patients underwent coronary artery bypass grafting more than twice as frequently
      as female patients (70.6% vs 29.4%). From 1988, total age-adjusted rate gradually
      increased for 10 years until 1997 (79.29 per 100,000 with 95% confidence interval
      70.88-87.71 per 100,000 in 1988, 131.31 per 100,000 with 95% confidence interval
      119.02-143.59 per 100,000 in 1997, P < .01), with ensuing rapid decline to nearly
      the lowest level at end of study in 2004 (83.01 per 100,000 with 95% confidence
      interval 75.68-90.33 per 100,000, P < .01). Although trends were similar across
      ethnicity and sex, female and ethnic minority patients had lower rates of bypass
      surgery than did male and white patients. CONCLUSIONS: Use of coronary artery
      bypass grafting has decreased dramatically in recent years, with even lower use
      among female and ethnic minority patients. This decline may be related to
      significant advances in percutaneous coronary interventions and improved medical
      treatment of atherosclerosis in the past 10 years.

PMID- 19853870
TI  - MB49 murine urothelial carcinoma: molecular and phenotypic comparison to human
      cell lines as a model of the direct tumor response to bacillus Calmette-Guerin.
AB  - PURPOSE: The mouse urothelial carcinoma cell line MB49 is widely used as an in
      vitro and in vivo model of urothelial carcinoma. Little comparative data exist on
      the molecular and phenotypic responses of this cell line relative to human cell
      lines. We compared the effect of bacillus Calmette-Guerin on the MB49 cell line
      relative to responses previously observed in the human urothelial carcinoma lines
      T24 (ATCC) and 253J. MATERIALS AND METHODS: Molecular end points in MB49 cells
      after bacillus Calmette-Guerin exposure were signaling pathway activation (NF
      kappaB, AP1 and C/EBP), gene expression (IL-6 and p21), HMGB1
      release/responsiveness and gene expression profiling at 6 hours. Phenotypic
      response end points were direct cytotoxicity using dye exclusion, viability on
      MTT assay, apoptotic sensitivity and cell cycle compartmentalization. RESULTS: NF
      kappaB, AP1, C/EBP, IL-6 and p21 reporter constructs were activated in MB49 cells
      in response to bacillus Calmette-Guerin. Gene expression profiles showed an
      inflammatory/immune clustering response. Bacillus Calmette-Guerin decreased cell
      viability and induced G1 cell cycle arrest. Treatment of MB49 cells with bacillus
      Calmette-Guerin induced caspase independent cell death while simultaneously
      decreasing sensitivity to pro-apoptotic agents. Cell death was associated with
      release of the necrotic cell death marker HMGB1. MB49 cells expressed HMGB1
      receptors and activated intracellular NF-kappaB signaling pathways in response to
      bacillus Calmette-Guerin. CONCLUSIONS: MB49 cells show molecular and phenotypic
      responses to bacillus Calmette-Guerin that replicate those observed in human
      urothelial carcinoma lines. MB49 cells appear to be an excellent model in which
      to study bacillus Calmette-Guerin as an antitumor agent for urothelial carcinoma.

PMID- 19853871
TI  - Dead zone dilemma.

PMID- 19853872
TI  - Large-scale dispersant leaching and effectiveness experiments with oils on calm
      water.
AB  - The use of dispersants to treat oil spills in calm seas is discouraged because
      there is insufficient 'mixing energy' to cause immediate dispersion of the oil.
      However, dispersants might be applied while the seas are calm, in the expectation
      that they would work later when sea states increase. The present study examined
      the persistence of dispersants in treated oil slicks on calm water in a large
      outdoor wave tank. Test slicks, pre-mixed with dispersant, were allowed to stand
      on static and flowing water for up to six days, after which their dispersibility
      was tested by exposing them to breaking waves. Results showed that thicker slicks
      exposed to calm water for up to six days dispersed completely with the addition
      of breaking waves. Thinner slicks and slicks exposed to water movement became
      less dispersible within two days. The loss of dispersibility was caused by
      dispersant loss rather than by oil weathering.

PMID- 19853873
TI  - Multi-scale modeling of CO2 dispersion leaked from seafloor off the Japanese
      coast.
AB  - A numerical simulation was conducted to predict the change of pCO(2) in the ocean
      caused by CO(2) leaked from an underground aquifer, in which CO(2) is
      purposefully stored. The target space of the present model was the ocean above
      the seafloor. The behavior of CO(2) bubbles, their dissolution, and the advection
      diffusion of dissolved CO(2) were numerically simulated. Here, two cases for the
      leakage rate were studied: an extreme case, 94,600 t/y, which assumed that a
      large fault accidentally connects the CO(2) reservoir and the seafloor; and a
      reasonable case, 3800 t/y, based on the seepage rate of an existing EOR site. In
      the extreme case, the calculated increase in DeltapCO(2) experienced by floating
      organisms was less than 300 ppm, while that for immobile organisms directly over
      the fault surface periodically exceeded 1000 ppm, if momentarily. In the
      reasonable case, the calculated DeltapCO(2) and pH were within the range of
      natural fluctuation.

PMID- 19853874
TI  - [Advanced age, female gender, infarction with ST segment elevation and absence of
      reperfusion therapy: a bad prognostic combination].

PMID- 19853875
TI  - [Neoplasms and HIV in the epidemic's third decade].

PMID- 19853876
TI  - Genotype of the CYBA promoter -930A/G, polymorphism C677T of the MTHFR and APOE
      genotype in patients with hypertensive disorders of pregnancy: an observational
      study.
AB  - BACKGROUND AND OBJECTIVE: Hypertensive disorders of pregnancy could be favoured
      by polymorphisms in genes affecting vascular physiology. The aim of our work was
      to study several variants in the genes regulating oxidative stress, plasma lipids
      metabolism and endothelial function (observational study). MATERIAL AND METHODS:
      We studied the -930A/G polymorphism of the CYBA gene promoter, the apolipoprotein
      E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T
      polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric
      hypertension (NPH) and 184 patients with preeclampsia (PE). RESULTS: The GG
      genotype of the CYBA gene promoter was present in 32.1% of the control
      population, 38.7% of patients with NPH (P=0.19) and 21.2% of the women with PE
      (P=0.03). A higher frequency of epsilon 3/epsilon 4 and epsilon 4/epsilon 4
      genotypes of APOE was observed in patients with PE or NPH compared with controls
      (P<0.01). There were no significant differences detected in genotype or allele
      distribution of the MTHFR, C677T polymorphism. APOE epsilon 3/epsilon 4 and
      epsilon 4/epsilon 4 genotypes had a worse lipoprotein profile characterized by
      higher plasma values of total cholesterol (P<0.05) and triglycerides (P<0.005).
      Despite no differences in MTHFR C677T polymorphism distribution, higher levels of
      plasma homocysteine were observed in patients with PE than in patients with NPH
      or controls. CONCLUSIONS: CYBA and APOE polymorphism showed a different
      distribution in the groups studied, while no differences were observed in MTHFR
      C677T polymorphism. APOE genotype was associated with changes in lipid and
      lipoprotein profiles in pregnant women.

PMID- 19853877
TI  - Gender-related explanatory models of depression: a critical evaluation of medical
      articles.
AB  - OBJECTIVES: Although research has consistently shown a higher prevalence of
      depression among women compared with men, there is a lack of consensus regarding
      explanatory factors for these gender-related differences. The aim of this paper
      was to analyse the scientific quality of different gender-related explanatory
      models of depression in the medical database PubMed. STUDY DESIGN: Qualitative
      and quantitative analyses of PubMed articles. METHODS: In a database search in
      PubMed for 2002, 82 articles on gender and depression were selected and analysed
      with qualitative and quantitative content analyses. In total, 10 explanatory
      factors and four explanatory models were found. The ISI Web of Science database
      was searched in order to obtain the citation number and journal impact factor for
      each article. RESULTS: The most commonly used gender-related explanatory model
      for depression was the biomedical model (especially gonadal hormones), followed
      by the sociocultural and psychological models. Compared with the other models,
      the biomedical model scored highest on bibliometric measures but lowest on
      measures of multifactorial dimensions and differences within the group of
      men/women. CONCLUSION: The biomedical model for explaining gender-related aspects
      of depression had the highest quality when bibliometric methods were used.
      However, the sociocultural and psychological models had higher quality than the
      biomedical model when multifactoriality and intersectionality were analysed.
      There is a need for the development of new methods in order to evaluate the
      scientific quality of research.

PMID- 19853878
TI  - [Estimating intracranial fluid dynamics using quantitative analyses of phase
      contrast magnetic resonance images].
AB  - OBJECTIVE: To estimate the dynamic relations between cerebrospinal fluid (CSF)
      and blood in the cerebral and spinal subarachnoid spaces and in the ventricles by
      quantifying phase contrast magnetic resonance imaging (MRI). MATERIAL AND
      METHODS: We analyzed 15 healthy volunteers during the same time of day and using
      the same magnetic field strength (3T). Each study consisted of four phase
      contrast sequences: two to calculate the CSF (aqueduct of Sylvius and the C2-C3
      perimedullary space) and two to calculate the blood flow (internal carotid and
      vertebral arteries, superior sagittal sinus, and straight sinus). We calculated
      the amplitude parameters (systolic volume, mean flow, pulsatility and compliance
      indexes, absolute pressure gradient, and ratio of CSF volume per cycle) and
      temporal parameters (delays respect to arterial flow). RESULTS: With respect to
      the input of arterial blood, the displacement of venous blood (22% and 38% of the
      cardiac cycle in the straight sinus and superior sagittal sinus, respectively)
      and of CSF (12% and 25% of the cardiac cycle in the C2-C3 perimedullary space and
      in the aqueduct of Sylvius, respectively) show the distribution of the
      pulsatility of the intracranial fluids. We calculated the indexes of compliance
      of the encephalic and medullary compartments in normal subjects. CONCLUSIONS: It
      is possible to quantitatively describe the dynamic relations between intracranial
      fluids and infer the elastic behavior of the brain and spinal canal by using flow
      velocity maps obtained with phase contrast MRI.

PMID- 19853879
TI  - Role of predation by zooplankton in transport and fate of protozoan (oo)cysts in
      granular activated carbon filtration.
AB  - The significance of zooplankton in the transport and fate of pathogenic organisms
      in drinking water is poorly understood, although many hints of the role of
      predation in the persistence of microorganisms through water treatment processes
      can be found in literature. The objective of this study was to assess the impact
      of predation by natural zooplankton on the transport and fate of protozoan
      (oo)cysts in granular activated carbon (GAC) filtration process. UV-irradiated
      unlabelled Cryptosporidium parvum and Giardia lamblia (oo)cysts were seeded into
      two pilot-scale GAC filtration columns operated under full-scale conditions. In a
      two-week period after seeding, a reduction of free (oo)cysts retained in the
      filter bed was observed. Zooplankton was isolated from the filter bed and
      effluent water on a 30 microm net before and during the two-week period after
      seeding; it was enumerated and identified. Rotifers, which are potential
      predators of (oo)cysts, accounted for the major part of the isolated zooplankton.
      Analytical methods were developed to detect (oo)cysts internalized in natural
      zooplankton isolated from the filter bed and effluent water. Sample sonication
      was optimized to disrupt zooplankton organisms and release internalized
      microorganisms. (Oo)cysts released from zooplankton after sonication were
      isolated by IMS and stained (EasyStain) for microscopic counting. Both
      Cryptosporidium and Giardia (oo)cysts were detected in association with
      zooplankton in the filter bed samples as well as in the effluent of GAC filters.
      The results of this study suggest that predation by zooplankton can play a role
      in the remobilization of persistent pathogens such as Cryptosporidium and Giardia
      (oo)cysts retained in GAC filter beds, and consequently in the transmission of
      these pathogens in drinking water.

PMID- 19853880
TI  - Influence of organic matter on the transport of Cryptosporidium parvum oocysts in
      a ferric oxyhydroxide-coated quartz sand saturated porous medium.
AB  - To assess the effect of organic matter on the transport of Cryptosporidium parvum
      oocysts in a geochemically heterogeneous saturated porous medium, we measured the
      breakthrough and collision efficiencies of oocysts as a function of dissolved
      organic matter concentration in a flow-through column containing ferric
      oxyhydroxide-coated sand. We characterized the surface properties of the oocysts
      and ferric oxyhydroxide-coated sand using microelectrophoresis and streaming
      potential, respectively, and the amount of organic matter adsorbed on the ferric
      oxyhydroxide-coated sand as a function of the concentration of dissolved organic
      matter (a fulvic acid isolated from Florida Everglades water). The dissolved
      organic matter had no significant effect on the zeta potential of the oocysts.
      Low concentrations of dissolved organic matter were responsible for reversing the
      charge of the ferric oxyhydroxide-coated sand surface from positive to negative.
      The charge reversal and accumulation of negative charge on the ferric
      oxyhydroxide-coated sand led to increases in oocyst breakthrough and decreases in
      oocyst collision efficiency with increasing dissolved organic matter
      concentration. The increase in dissolved organic matter concentration from 0 to
      20mg L(-1) resulted in a two-fold decrease in the collision efficiency.

PMID- 19853881
TI  - Macromolecule mediated transport and retention of Escherichia coli O157:H7 in
      saturated porous media.
AB  - The role of extracellular macromolecules on Escherichia coli O157:H7 transport
      and retention was investigated in saturated porous media. To compare the relative
      transport and retention of E. coli cells that are macromolecule rich and
      deficient, macromolecules were partially cleaved using a proteolytic enzyme.
      Characterization of bacterial cell surfaces, cell aggregation, and experiments in
      a packed sand column were conducted over a range of ionic strength (IS). The
      results showed that macromolecule-related interactions contribute to retention of
      E. coli O157:H7 and are strongly linked to solution IS. Under low IS conditions
      (IS < or = 0.1 mM), partial removal of the macromolecules resulted in a more
      negative electrophoretic mobility of cells and created more unfavorable
      conditions for cell-quartz and cell-cell interactions as suggested by Derjaguin
      Landau-Verwey-Overbeek (DLVO) interaction energy profiles and cell aggregation
      kinetics. Consequently, less retention was observed for enzyme treated cells in
      the corresponding column experiments. In addition, a time-dependent deposition
      process (i.e., ripening) was observed for untreated cells, but not for treated
      cells, supporting the fact that the macromolecules enhanced cell-cell
      interactions. Additional column experiments for untreated cells under favorable
      conditions (IS > or = 1 mM) showed that a significant amount of the cells were
      reversibly retained in the column, which contradicts predictions of DLVO theory.
      Furthermore, a non-monotonic cell retention profile was observed under favorable
      attachment conditions. These observations indicated that the presence of
      macromolecules hindered irreversible interactions between the cells and the
      quartz surface.

PMID- 19853882
TI  - Synthesis and NMR properties of the first boron analogues of uracil.
AB  - Synthesis of 4-hydroxyborauracil and 4-hydroxy-3-methylborauracil, the first
      boron analogues of uracil, and comparison of their 1H and 13C NMR properties with
      those of uracil, are presented. The analyses of NMR-monitored boron compound
      alcohol and boron compound-amine interactions pointed to the existence of sp3
      hybridized, B,B-bis-methoxyborauracils and pyridine-/n-butylamine-borauracils ate
      complexes in solution.

PMID- 19853883
TI  - Greywater disinfection with the environmentally friendly Hydrogen Peroxide Plus
      (HPP).
AB  - Hydrogen Peroxide Plus (HPP) is a newly developed, stabilized-H(2)O(2)-based
      compound. This study was aimed at determining the disinfection efficiency of HPP
      in greywater (GW), assessing HPP dose requirements and evaluating the feasibility
      of its use in small-scale GW-treatment systems. Fecal coliforms were the most
      sensitive to treatment, followed by somatic coliphages and F+ bacteriophages. The
      calculated HPP dose required to reduce fecal coliform counts by 99% was 125mg
      H(2)O(2)L(-1), with a contact time of 35min. The use of HPP was found feasible
      and comparable to the use of chlorine for small systems with a flow rate of
      5m(3)d(-1). HPP is suggested as an alternative for GW disinfection in small
      communities and private houses.

PMID- 19853884
TI  - Molecular phylogenies and evolutionary behavior of AhR (aryl hydrocarbon
      receptor) pathway genes in aquatic animals: implications for the toxicology
      mechanism of some persistent organic pollutants (POPs).
AB  - Phylogenetic analysis of AhR pathway genes and their evolutionary rate variations
      were studied on aquatic animals. The gene sequences for the proteins involved in
      this pathway were obtained from four major phylogenetic groups, including
      bivalvia, amphibian, teleostei and mammalia. These genes were distributed under
      four major steps of toxicology regulation: formation of cytosolic complex,
      translocation of AhR, heterodimerization of AhR and induction of CYP1A. The NJ,
      MP, and ML algorithm were used on protein coding DNA sequences to deduce the
      evolutionary relationship for the respective AhR pathway gene among different
      aquatic animals. The rate of non-synonymous nucleotide substitutions per non
      synonymous site (d(N)) and synonymous nucleotide substitutions per synonymous
      site (d(S)) were calculated for different clade of the respective phylogenetic
      tree for each AhR pathway gene. The phylogenetic analysis suggests that
      evolutionary pattern of AhR pathway genes in aquatic animals is characterized
      mainly through gene duplication events or alterative splicing. The d(N) values
      indicate that all AhR pathway genes are well conserved in aquatic animals, except
      for CYP1A gene. Furthermore, compare with other aquatic animals, the d(N) value
      indicates that AhR pathway genes of fish are less conserved, and these genes
      likely go through an adaptive evolution within aquatic animals.

PMID- 19853885
TI  - Mechanism study on the frequent variations of cell-bound microcystins in
      cyanobacterial blooms in Lake Taihu: implications for water quality monitoring
      and assessments.
AB  - Although Microcystis-based toxins have been intensively studied, previous studies
      using laboratory cultures of Microcystis strains are difficult to explain the
      phenomenon that microcystin concentrations and toxin variants in natural blooms
      differ widely and frequently within a short-term period. The present study was
      designed to unravel the mechanisms for the frequent variations of intracellular
      toxins related to the differences in cyanobacterial colonies during bloom seasons
      in Lake Taihu, China. Monitoring of Microcystis colonies during warm seasons
      indicated that the variations in microcystins in both concentrations and toxin
      species were associated with the frequent alteration of Microcystis colonies in
      Lake Taihu. High concentration of microcystins in the blooms was always
      associated with two Microcystis colonies, Microcystis flos-aquae and Microcystis
      aeruginosa, whereas when Microcystis wesenbergii was the dominant colonial type,
      the toxin production of the blooms was low. Additionally, environmental factors
      such as temperature and nutrition were also shown to have an effect on the toxin
      production of the blooms, and may also potentially influence the Microcystis
      species present. The results of the present study provides insight into a new
      consideration for quick water quality monitoring, assessment and risk alert in
      cyanobacterium- and toxin-contaminated freshwaters, which will be beneficial not
      only for water agencies but also for public health.

PMID- 19853887
TI  - Quantitative assessment of intrinsic groundwater vulnerability to contamination
      using numerical simulations.
AB  - Intrinsic vulnerability assessment to groundwater contamination is part of
      groundwater management in many areas of the world. However, popular assessment
      methods estimate vulnerability only qualitatively. To enhance vulnerability
      assessment, an approach for quantitative vulnerability assessment using numerical
      simulation of water flow and solute transport with transient boundary conditions
      and new vulnerability indicators are presented in this work. Based on a
      conceptual model of the unsaturated underground with distinct hydrogeological
      layers and site specific hydrological characteristics the numerical simulations
      of water flow and solute transport are applied on each hydrogeological layer with
      standardized conditions separately. Analysis of the simulation results reveals
      functional relationships between layer thickness, groundwater recharge and
      transit time. Based on the first, second and third quartiles of solute mass
      breakthrough at the lower boundary of the unsaturated zone, and the solute
      dilution, four vulnerability indicators are extracted. The indicator transit time
      t(50) is the time were 50% of solute mass breakthrough passes the groundwater
      table. Dilution is referred as maximum solute concentration C(max) in the
      percolation water when entering the groundwater table in relation to the injected
      mass or solute concentration C(0) at the ground surface. Duration of solute
      breakthrough is defined as the time period between 25% and 75% (t(25%)-t(75%)) of
      total solute mass breakthrough at the groundwater table. The temporal shape of
      the breakthrough curve is expressed with the quotient (t(25%)-t(50%))/(t(25%)
      t(75%)). Results from an application of this new quantitative vulnerability
      assessment approach, its advantages and disadvantages, and potential benefits for
      future groundwater management strategies are discussed.

PMID- 19853886
TI  - Evaluation of home lead remediation in an Australian mining community.
AB  - In 1994 a comprehensive program was established to reduce children's blood lead
      levels in Broken Hill, NSW, Australia. Home remediation (abatement of lead
      hazards in a child's home) was included as part of a case management strategy for
      children with blood lead levels >or=15 microg/dL. Children with blood lead levels
      >or=30 microg/dL were offered immediate home remediation. Children with blood
      lead levels of 15-29 microg/dL were allocated to 'immediate' or 'delayed' home
      remediation; a subset of these participated in a randomized controlled trial
      (RCT) to evaluate the effectiveness of home remediation for reducing blood lead
      levels. One hundred and seventeen children received home remediation. One hundred
      and thirteen returned for follow-up blood tests, 88 of whom participated in the
      RCT. On average children's blood lead levels decreased by 1.7 microg/dL (10%) in
      the 6 months after remediation and by 2.2 microg/dL (13%) in the 6-12 months
      after remediation. However, remediation did not significantly change the rate of
      decline in blood lead levels (P=0.609). There was no evidence of association
      between change in children's blood lead levels and changes in lead loading in
      their homes. The results are consistent with the published literature, which
      suggests that home remediation does not reduce children's exposure to lead
      sufficiently to cause a moderate or greater decrease in their blood lead level.
      In communities where lead is widely dispersed, the study suggests that it is
      important to assess potential sources and pathways by which children are exposed
      to lead when developing an intervention plan, and the need for multiple
      interventions to effectively reduce blood lead levels. The findings reinforce the
      ongoing need for rigorous epidemiological evaluation of lead management programs
      to improve the evidence base, and for effective primary prevention to avoid
      children being exposed to lead in the first place.

PMID- 19853888
TI  - Traffic pollution affects tree-ring width and isotopic composition of Pinus
      pinea.
AB  - This study presents new evidence that radiocarbon, combined with
      dendrochronological and stable isotopes analysis in tree rings and needles, can
      help to better understand the influence of pollution on trees. Pinus pinea
      individuals, adjacent to main roads in the urban area of Caserta (South Italy)
      and exposed to large amounts of traffic exhaust since 1980, were sampled and the
      time-related trend in the growth residuals was estimated. We found a consistent
      decrease in the ring width starting from 1980, with a slight increase in
      delta(13)C value, which was considered to be a consequence of environmental
      stress. No clear pattern was identified in delta(15)N, while an increasing effect
      of the fossil fuel dilution on the atmospheric bomb-enriched (14)C background was
      detected in tree rings, possibly as a consequence of the increase in traffic
      exhausts. Our findings suggested that radiocarbon is a very sensitive tool to
      investigate small-scale (i.e. traffic exhaust at the level crossing) and large
      scale (urban area pollution) induced disturbances.

PMID- 19853889
TI  - Antimicrobial resistance of fecal bacteria in waters of the Seine river watershed
      (France).
AB  - We studied the prevalences of antimicrobial resistance (AR) and multiple
      antimicrobial resistance (MAR) among the fecal bacteria found in the rivers of a
      large watershed under strong anthropogenic pressures, the Seine river watershed
      (France). Two groups of fecal indicator bacteria, Escherichia coli and intestinal
      enterococci, were tested for their susceptibility to 16 and 10 antimicrobials
      respectively, using the disk diffusion method. We found that 42% of the 214 E.
      coli river isolates were AR (resistant to at least one antimicrobial) and 35%
      were MAR (resistant to at least two antimicrobials). Among the 148 intestinal
      enterococci isolates from rivers, 83% were AR and 49% were MAR. We also
      investigated the sources of AR fecal bacteria found in the rivers of the
      watershed. A total of 715 E. coli isolates and 476 intestinal enterococci
      isolates were collected in point sources (municipal and hospital wastewaters) and
      non-point sources (surface runoff and soil leaching waters from agricultural or
      forest areas). For E. coli, the prevalence of AR differed widely from source to
      source and ranked in this order: hospital wastewaters (71%)>municipal wastewaters
      (44%)>agricultural non-point sources (16%)>forest non-point sources (2%). The
      prevalence of MAR ranked similarly, and the same trend was observed for
      intestinal enterococci. The AR level of fecal bacteria in the sources was related
      to their expected exposure level to antimicrobials before their release into the
      environment. A MAR index was calculated for every source and a good
      discrimination between them was thus obtained. At the global scale of the Seine
      river watershed, domestic wastewaters seemed more likely to be the predominant
      source of the AR fecal bacteria found in the rivers. This was corroborated by the
      similarity of the MAR indices from river and municipal wastewater isolates for
      both fecal indicators.

PMID- 19853890
TI  - 'Pergularain e I'--a plant cysteine protease with thrombin-like activity from
      Pergularia extensa latex.
AB  - Pergularain e I, a cysteine protease with thrombin-like activity, was purified by
      ion exchange chromatography from the latex of Pergularia extensa. Its homogeneity
      was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE), native PAGE and reverse-phase high-performance liquid chromatography
      (RP-HPLC). The molecular mass of pergularain e I by matrix-assisted laser
      desorption ionization-time of flight (MALDI-TOF) was found to be 23.356 kDa and
      the N-terminal sequence is L-P-H-D-V-E. Pergularain e I is a glycoprotein
      containing approximately 20% of carbohydrate. Pergularain e I constituted 6.7% of
      the total protein with a specific activity of 9.5 units/mg/min with a 2.11-fold
      increased purity. Proteolytic activity of the pergularain e I was completely
      inhibited by iodoacetic acid (IAA). Pergularain e I exhibited procoagulant
      activity with citrated plasma and fibrinogen similar to thrombin. Pergularain e I
      increases the absorbance of fibrinogen solution in concentration-dependent and
      time-dependent manner. At 10 microg concentration, an absorbance of 0.48 was
      reached within 10 min of incubation time. Similar absorbance was observed when
      0.2 NIH units of thrombin were used. Thrombin-like activity of pergularain e I is
      because of the selective hydrolysis of A alpha and B beta chains of fibrinogen
      and gamma-chain was observed to be insusceptible to hydrolysis. Molecular masses
      of the two peptide fragments released from fibrinogen due to the hydrolysis by
      pergularain e I at 5-min incubation time were found to be 1537.21 and 1553.29 and
      were in close agreement with the molecular masses of 16 amino acid sequence of
      fibrinopeptide A and 14 amino acid sequence of fibrinopeptide B, respectively.
      Prolonged fibrinogen-pergularain e I incubation releases additional peptides and
      their sequence comparison of molecular masses of the released peptides suggested
      that pergularain e I hydrolyzes specifically after arginine residues.

PMID- 19853891
TI  - Risk factors for failure of heparin thromboprophylaxis in patients with acute
      traumatic spinal cord injury.
AB  - Venous thromboembolism (VTE) is a well-recognized complication of Acute Traumatic
      Spinal Cord Injury (ATSCI). Despite prophylaxis by heparins, VTE occurs in a
      substantial number of ATSCI patients without an obvious explanation. In this
      matched case-control study we examined whether thrombophilia and other risk
      factors are associated with failure of thromboprophylaxis. Cases and controls
      receiving heparin thromboprophylaxis were selected from consecutively admitted
      ATSCI patients. Patients who developed a new, objectively confirmed, symptomatic
      VTE despite prophylaxis at hospital were matched by gender, age, level and
      mechanism of ATSCI with 2-3 controls without VTE. Patients were interviewed about
      VTE risk factors and tested for factor V Leiden (FVL), prothrombin G20210A (PT),
      methylenetetrahydrofolate reductase C677T homozygosity (MTHFR), lupus
      anticoagulant, homocysteine (Hcy) and plasma factor VIII (FVIII) levels. Twenty
      two patients with new VTE episodes and 64 controls were ascertained. The total
      number of gene alterations for MTHFR, FVL and PT or elevated levels of Hcy or
      FVIII was significantly more common in patients compared to controls (82% vs.
      48%, p=0.006). Multiple logistic regression proved the PT mutation, a positive
      family history of thrombosis and elevated levels of either FVIII or Hcy to be
      predictors of thrombosis. CONCLUSION: A positive family history of VTE,
      carriership of the prothrombin mutation and elevated FVIII or Hcy levels were
      significantly associated with failure to prevent VTE by heparin therapy following
      ATSCI. Testing for thrombophilia in patients with ATSCI and possibly a more
      intense thromboprophylactic regimen seem desirable but need to be verified by a
      prospective study.

PMID- 19853892
TI  - Home treatment in pulmonary embolism.
AB  - BACKGROUND: Limited data exist on the feasibility of providing outpatient care to
      patients with acute pulmonary embolism (PE). METHODS: We conducted a multicenter
      randomized clinical trial in acute symptomatic PE to compare the efficacy and
      safety of early discharge versus standard hospitalization. A clinical prediction
      rule was used to identify low-risk patients. All patients were followed for three
      months. The primary outcomes were venous thromboembolic recurrences, major and
      minor bleeding, and overall mortality. RESULTS: One hundred and thirty two low
      risk patients with acute symptomatic PE were randomized to early discharge (n=72)
      or standard hospitalization (n=60). Overall mortality was 4.2% (95% CI, 0.5-8.9)
      in the early discharge group and 8.3% (95% CI, 1.1-15) in the standard
      hospitalization group (Relative Risk (RR) 0.5; 95% confidence interval [CI], 0.12
      2.01). Non-fatal recurrences were 2.8% (95% CI, 1.1-6.6) in the early discharge
      group and 3.3% (95% CI, 1.3-8%) in the standard hospitalization group (RR 0.8;
      95% CI, 0.12-5.74). The rates of clinically relevant bleeding were 5.5% in the
      early discharge group and 5% in the standard hospitalization group (P=0.60).
      Short-term mortality was 2.8% (95% CI, 0.8-9.6%) in the early discharge group as
      compared with 0% in the standard hospitalization group. Based on the rate of
      short-term death in a carefully selected population, the study was suspended.
      CONCLUSIONS: In spite of the number of complications in patients with acute
      symptomatic PE randomized to standard hospitalization or early discharge did not
      differ significantly. The rate of short-term mortality was unexpectedly high in a
      (a priori) low-risk group of patients with acute PE. The accuracy of clinical
      prediction scores needs to be validated in well designed clinical trials.
      (ClinicalTrials.gov number, NCT00214929.).

PMID- 19853894
TI  - The role of macrophages in the disappearance of Meckel's cartilage during
      mandibular development in mice.
AB  - Meckel's cartilage is a supporting tissue in the embryonic mandible that
      disappears during development; however, the precise mechanisms of this
      disappearance process are still undetermined. In this study, we observed
      morphological changes of Meckel's cartilage with development and analyzed the
      factors which might be related to this process. Meckel's cartilage of ICR strain
      mice from 14 to 19 days gestation (E14-19) were used in this study. Histological
      and immunohistochemical studies indicated the decrease in the amount of sulfated
      glycoconjugates and the localization of type I collagen in the Meckel's cartilage
      matrix during development. Chondrocytes also expressed high acid phosphatase
      activities at these stages. An organ culture study indicated that Meckel's
      cartilage at E17 disappeared during the cultivation period, while the cartilage
      at E14 did not disappear. Massive penetration of macrophages into the
      perichondrium was detected at E16. RT-PCR analysis of Meckel's cartilage
      indicated the expression of interleukin-1beta, type I collagen, MMP-9 at E17, but
      not at E14. MIP-1alpha, the candidate molecule for macrophage chemoattractant
      factor, was expressed at E14. These results indicated the dynamic matrix changes
      of Meckel's cartilage during development and suggested that the functional
      changes of chondrocytes in synthesis of type I collagen might be induced by
      interleukin-1beta secreted by the penetrating macrophages.

PMID- 19853893
TI  - Flow-based measurements of von Willebrand factor (VWF) function: binding to
      collagen and platelet adhesion under physiological shear rate.
AB  - INTRODUCTION: VWF circulates in plasma as a series of heterogeneous multimers,
      mediating platelet tethering, translocation and finally adhesion to areas of
      injured endothelium under physiological high arterial blood flow. VWF-platelet
      binding requires conformational changes in VWF, which are induced by
      immobilization and shear. Because of unavailability of a simple flow-based
      measurement system, VWF activity assays are generally performed under static
      conditions. We describe an easily reproducible in vitro flow-chamber model using
      commercially available flow devices to examine VWF-collagen binding and VWF
      mediated platelet adhesion under physiological flow conditions. METHODS: The
      collagen surface of the flow-chamber was analyzed by atomic force microscopy.
      Collagen-bound VWF was characterized by multimer analysis and multi labelling
      immunofluorescence detection of exposed GPIb binding domains. Platelet adhesion
      was captured by time-lapse microscopy. RESULTS: The described flow-chamber system
      facilitates multimer analysis of collagen-bound VWF, whereas all VWF multimers
      bound to collagen under physiological low to high shear rates. Multi labelling
      immunofluorescence detection exhibited exposed GPIb binding domains co-localized
      with VWF molecules. VWF-dependent platelet adhesion using time-lapse microscopy
      showed values comparable to experiments done with whole blood, and platelet
      adhesion was dependent on the VWF concentration. CONCLUSIONS: The established
      flow-chamber model represents an easy-to-set-up and customized tool for the
      characterization of VWF-binding to collagen as well as the determination of VWF
      dependent platelet adhesion under defined flow conditions in real-time.

PMID- 19853895
TI  - Abelardo Gallego (1879-1930) and his contributions to histotechnology: the
      Gallego stains.
AB  - The Gallego general tissue stain is used in histology and histopathology and
      stains beautifully connective tissue, in which all nuclei are stained in magenta
      red, epithelial cytoplasm in red-yellow, connective tissue is stained in
      brilliant green, muscle in olive green, and keratinized epithelium and blood in
      grass green. There is also Gallego's method for differential staining of elastic
      tissue that enables a complete differentiation between elastic and collagenous
      connective tissue. The elastic tissue is stained in brilliant fuschin red, while
      collagen is stained in brilliant green. Abelardo Gallego was born in Spain on
      September 10, 1879. He was appointed as professor of Pharmacology and
      Therapeutics at the Faculty of Veterinary Medicine at the University of Santiago
      de Compostela, Spain, and in 1921 became full-time professor of Histology and
      Pathology in Madrid supported by Ramon y Cajal. Gallego conducted extensive
      research into veterinary pathology. Don Abelardo was a quiet, reserved, but
      friendly, sensitive, optimistic and persistent person. Weakened by a bout of
      bronchitis, Gallego died aged 51 on February 3, 1930, and was buried at the
      Almudena Cemetery, in Madrid. Gallego was one of the most outstanding scientists
      of Spanish veterinary medicine and some of his achievements are reviewed.

PMID- 19853898
TI  - Uterine sarcomas: a review.
AB  - OBJECTIVE: Uterine sarcomas are rare tumors that account for 3% of uterine
      cancers. Their histopathologic classification was revised by the World Health
      Organization (WHO) in 2003. A new staging system has been recently designed by
      the International Federation of Gynecology and Obstetrics (FIGO). Currently,
      there is no consensus on risk factors for adverse outcome. This review summarizes
      the available clinicopathological data on uterine sarcomas classified by the WHO
      diagnostic criteria. METHODS: Medline was searched between 1976 and 2009 for all
      publications in English where the studied population included women diagnosed of
      uterine sarcomas. RESULTS: Since carcinosarcomas (malignant mixed mesodermal
      tumors or MMMT) are currently classified as metaplastic carcinomas,
      leiomyosarcomas remain the most common uterine sarcomas. Exclusion of several
      histologic variants of leiomyoma, as well as "smooth muscle tumors of uncertain
      malignant potential," frequently misdiagnosed as sarcomas, has made apparent that
      leiomyosarcomas are associated with poor prognosis even when seemingly confined
      to the uterus. Endometrial stromal sarcomas are indolent tumors associated with
      long-term survival. Undifferentiated endometrial sarcomas exhibiting nuclear
      pleomorphism behave more aggressively than tumors showing nuclear uniformity.
      Adenosarcomas have a favorable prognosis except for tumors showing myometrial
      invasion or sarcomatous overgrowth. Adenofibromas may represent well
      differentiated adenosarcomas. The prognosis of carcinosarcomas (which are
      considered here in a post-script fashion) is usually worse than that of grade 3
      endometrial carcinomas. Immunohistochemical expression of Ki67, p53, and p16 is
      significantly higher in leiomyosarcomas and undifferentiated endometrial sarcomas
      than in endometrial stromal sarcomas. CONCLUSIONS: Evaluation of H&E stained
      sections has been equivocal in the prediction of behavior of uterine sarcomas.
      Immunohistochemical studies of oncoproteins as well as molecular analysis of non
      random translocations will undoubtedly lead to an accurate and prognostically
      relevant classification of these rare tumors.

PMID- 19853899
TI  - Trial design for evaluation of novel targeted therapies.
AB  - OBJECTIVES: The vast number of novel targeted therapies available for testing in
      the United States dictates that a more efficient system aimed at identifying
      promising agents for phase III testing needs to be developed. Alternatives to
      traditional phase II trial design including alternative end points, randomized
      designs, biomarkers, and imaging tools are discussed. METHODS: Novel techniques
      for phase II trials were researched in the literature. Incorporation of surrogate
      endpoints and novel approaches were identified. RESULTS: Phase II trials are
      traditionally designed evaluating response rates compared to historical controls.
      In addition to identifying surrogates, novel approaches to phase II study design
      need to be tested. Incorporation of biomarkers into phase II trial design could
      allow for more accurate identification of patients who will benefit from targeted
      therapies. Tumor response as measured by anatomic imaging has been used to
      measure therapeutic efficacy in the era of cytotoxic drugs. Fluorodeoxyglucose
      (FDG)-positron emission tomography (PET) however, has been used increasingly in
      the evaluation of biologic responses. CONCLUSIONS: Alternatives to traditional
      phase II trial design including alternative end points, randomized designs,
      biomarkers, and imaging tools should allow ineffective agents to be discarded and
      promising agents to undergo further investigation.

PMID- 19853900
TI  - Factors affecting spontaneous reduction of corpora lutea and twin embryos during
      the late embryonic/early fetal period in multiple-ovulating dairy cows.
AB  - Spontaneous reduction of advanced twin embryos has been described in high
      producing, Holstein-Fresian (Bos taurus) dairy herds. The first objective of the
      current study was to determine whether management and cow factors could have an
      effect on such a reduction in twin pregnancies during the early fetal period.
      Because loss of a corpus luteum was noted in cows suffering twin reduction, we
      expanded our study to include multiple-ovulating cows carrying singletons.
      Pregnancy was diagnosed and confirmed from Days 28 to 34 and 56 to 62
      postinsemination. Sixty-nine (23.5%) of 293 pregnant cows with two corpora lutea
      carrying singletons and 132 (28.4%) of 464 twin pregnancies recorded on first
      pregnancy diagnosis subsequently lost one of the corpora lutea or one of the
      embryos, respectively. Thirty-four (25.8%) of the 132 twin pregnancies suffering
      embryo reduction lost one corpus luteum along with the embryo. Corpus luteum
      reduction always occurred in the ovary ipsilateral to the gravid horn suffering
      embryo reduction. Binary logistic regressions were performed considering corpus
      luteum and embryo reduction as dependent variables in single and twin
      pregnancies, respectively, and several management- and cow-related factors as
      independent variables. In cows carrying singletons, the risk of corpus luteum
      reduction was 14.3 (1/0.07) times lower for a given herd, whereas the interaction
      season by laterality significantly affected corpus luteum reduction such that in
      cows with two corpora lutea ipsilateral to the horn of pregnancy, the risk of
      reduction decreased during the winter period. In cows carrying twins, ipsilateral
      twin pregnancies were 3.45 (1/0.29) times more likely to undergo the loss of one
      embryo than bilateral twin pregnancies. As an overall conclusion, both corpora
      lutea and embryos were vulnerable to the effects of stress factors during the
      early fetal period in cows maintaining their pregnancies. A strong unilateral
      relationship between the corpus luteum and the conceptus was also observed.

PMID- 19853901
TI  - Epidermal growth factor, transforming growth factor-alpha, and epidermal growth
      factor receptor expression and localization in the canine endometrium during the
      estrous cycle and in bitches with pyometra.
AB  - Gene expression and immunohistochemical localization of epidermal growth factor
      (EGF), transforming growth factor-alpha (TGF-alpha), and epidermal growth factor
      receptor (EGF-R) were compared between the endometrium of bitches (Canis
      familiaris) with pyometra accompanied by cystic endometrial hyperplasia (CEH) and
      that of healthy bitches at similar stages of the estrous cycle. In normal
      bitches, endometrial TGF-alpha mRNA levels were highest at proestrus and
      gradually decreased as the cycle progressed to anestrus. Epidermal growth factor
      receptor mRNA levels were not significantly affected by the stage of the estrous
      cycle. Epidermal growth factor mRNA levels were higher at Day 35 of diestrus than
      at other stages of the estrous cycle (P<0.05). In bitches with pyometra,
      endometrial TGF-alpha and EGF-R mRNA levels did not differ significantly from
      those at diestrus in normal bitches, but EGF mRNA levels were lower than those at
      Day 35 of diestrus in normal bitches (P<0.05). In normal bitches, positive
      immunohistochemical staining for TGF-alpha, EGF, and EGF-R was mainly present in
      the glandular and luminal epithelial cells of the endometrium. In contrast, in
      bitches with pyometra, immunoreactivity for EGF was clearly present in
      endometrial stromal cells. Inflammatory cells that had infiltrated the
      endometrial stroma stained strongly for TGF-alpha and EGF-R. Luminal and
      glandular epithelial cells also stained positive for EGF-R. In conclusion,
      expression of TGF-alpha by inflammatory cells and a low level of expression and
      differential localization of EGF may be involved in aberrant growth of
      endometrial glands and development of CEH.

PMID- 19853903
TI  - Testis stereology, seminiferous epithelium cycle length, and daily sperm
      production in the ocelot (Leopardus pardalis).
AB  - Similar to most wild felids, the ocelot (Leopardus pardalis) is an endangered
      species. However, knowledge regarding reproductive biology of the ocelot is very
      limited. Germ cell transplantation is an effective technique for investigating
      spermatogenesis and stem cell biology in mammals, and the morphologic
      characterization of germ cells and knowledge of cycle length are potential tools
      for tracking the development of transplanted germ cells. Our goal was to
      investigate basic aspects related to testis structure, particularly
      spermatogenesis, in the ocelot. Four adult males were used. After unilateral
      orchiectomy, testis samples were routinely prepared for histologic, stereologic,
      and autoradiographic analyses. Testis weight and the gonadosomatic index were
      11+/-0.6g and 0.16+/-0.01%, respectively, whereas the volume density of
      seminiferous tubules and Leydig cells was 83.2+/-1.6% and 9.8+/-1.5%. Based on
      the acrosomic system, eight stages of spermatogenesis were characterized, and
      germ cell morphology was very similar to that of domestic cats. Each
      spermatogenic cycle lasted 12.5+/-0.4 d, and the entire spermatogenic process
      lasted 56.3+/-1.9 d. Individual Leydig cell volume was 2522mum(3), whereas the
      number of Leydig and Sertoli cells per gram of testis was 38+/-5x10(6) and 46+/
      3x10(6). Approximately 4.5 spermatids were found per Sertoli cell, whereas daily
      sperm production per gram of testis was 18.3+/-1x10(6), slightly higher than
      values reported for other felids. The knowledge obtained in this study could be
      very useful to the preservation of the ocelot using domestic cat testes to
      generate and propagate the ocelot genome.

PMID- 19853902
TI  - Oocyte quality and estradiol supplementation affect in vitro maturation success
      in the white-tailed deer (Odocoileus virginianus).
AB  - White-tailed deer oocyte biology is not well documented. The objective of this
      study was to determine (1) the influence of estradiol (E(2)) supplementation on
      meiotic resumption and the ability to "rescue" poorer quality (lower grade)
      oocytes and (2) the kinetics of oocyte nuclear maturation in vitro in the white
      tailed deer. In Experiment 1, immature oocytes harvested during hunting-culling
      operations were cultured for 24h in the presence or absence of E(2). Incubation
      in 1mug/mL E(2) promoted nuclear maturation (to telophase I, TI; or to metaphase
      II, MII) in a higher proportion of Grade 1 oocytes ( approximately 77%; P<0.05)
      compared with that in Grade 2 or Grade 3 counterparts ( approximately 51%). For
      Grades 2 and 3 oocytes, there was no advantage (P>0.05) for E(2) supplementation
      in reaching TI/MII. In Experiment 2, Grade 1 oocytes were cultured in the
      presence of E(2) and nuclear status evaluated at 0, 3, 6, 12, and 24h of in vitro
      incubation. At 0h,>70% of oocytes already had undergone germinal vesicle
      breakdown. After 12h, approximately 70% of oocytes had reached metaphase I of
      nuclear maturation, with approximately 75% achieving TI/MII by 24h in vitro. In
      summary, adding E(2) to an in vitro maturation (IVM) culture system for white
      tailed deer was advantageous, but only for the highest quality oocytes, with
      approximately 75% achieving nuclear maturation. In contrast, E(2) supplement did
      not benefit lower-grade oocytes, half of which will reach MII, with the other
      half failing. Under the described culture conditions, good-quality white-tailed
      deer oocytes achieve nuclear maturation over a time duration comparable with that
      reported in other ungulates.

PMID- 19853904
TI  - Cryopreservation of immature porcine testis tissue to maintain its developmental
      potential after xenografting into recipient mice.
AB  - The purpose of this study was to develop effective strategies for cooling and
      cryopreservation of immature porcine testis tissue that maintain its
      developmental potential. Testes from 1-wk-old piglets (Sus domestica) were
      subjected to 1 of 12 cooling/cryopreservation protocols: as intact testes,
      cooling at 4 degrees C for 24, 48, or 72h (Experiment 1); as fragments,
      programmed slow-freezing with dimethyl sulfoxide (DMSO), glycerol, or ethylene
      glycol (Experiment 2); or solid-surface vitrification using DMSO, glycerol, or
      ethylene glycol, each using 5-, 15-, or 30-min cryoprotectant exposure times
      (Experiment 3). For testis tissue xenografting, four immunodeficient recipient
      mice were assigned to each protocol, and each mouse received eight grafts.
      Recipient mice were killed 16 wk after grafting to assess the status of graft
      development. Based on morphology and in vitro assessment of cell viability,
      cooling of testis tissue for up to 72h maintained structural integrity, cell
      viability, in vivo growth, and developmental potential up to complete
      spermatogenesis comparable with that of fresh tissue (control). In frozen-thawed
      testis tissues, higher numbers of viable cells were present after programmed slow
      freezing using glycerol compared with that after DMSO or ethylene glycol
      (P<0.001). Among the vitrified groups, exposure to DMSO for 5min yielded
      numerically higher viable cell numbers than that of other groups. Cryopreserved
      tissue fragments recovered after xenografting had normal spermatogenesis; germ
      cells advanced to round and elongated spermatids after programmed slow-freezing
      using glycerol, as well as after vitrification using glycerol with 5- or 15-min
      exposures, or using DMSO for a 5-min exposure.

PMID- 19853907
TI  - Gastrointestinal hormones and weight management.

PMID- 19853905
TI  - The relationship of neurogenesis and growth of brain regions to song learning.
AB  - Song learning, maintenance and production require coordinated activity across
      multiple auditory, sensory-motor, and neuromuscular structures. Telencephalic
      components of the sensory-motor circuitry are unique to avian species that engage
      in song learning. The song system shows protracted development that begins prior
      to hatching but continues well into adulthood. The staggered developmental
      timetable for construction of the song system provides clues of subsystems
      involved in specific stages of song learning and maintenance. Progressive events,
      including neurogenesis and song system growth, as well as regressive events such
      as apoptosis and synapse elimination, occur during periods of song learning and
      the transitions between variable and stereotyped song during both development and
      adulthood. There is clear evidence that gonadal steroids influence the
      development of song attributes and shape the underlying neural circuitry. Some
      aspects of song system development are influenced by sensory, motor and social
      experience, while other aspects of neural development appear to be experience
      independent. Although there are species differences in the extent to which song
      learning continues into adulthood, growing evidence suggests that despite
      differences in learning trajectories, adult refinement of song motor control and
      song maintenance can require remarkable behavioral and neural flexibility
      reminiscent of sensory-motor learning.

PMID- 19853906
TI  - Effects of liraglutide in the treatment of obesity: a randomised, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: The frequency of obesity has risen dramatically in recent years but
      only few safe and effective drugs are currently available. We assessed the effect
      of liraglutide on bodyweight and tolerability in obese individuals without type 2
      diabetes. METHODS: We did a double-blind, placebo-controlled 20-week trial, with
      open-label orlistat comparator in 19 sites in Europe. 564 individuals (18-65
      years of age, body-mass index 30-40 kg/m2) were randomly assigned, with a
      telephone or web-based system, to one of four liraglutide doses (1.2 mg, 1.8 mg,
      2.4 mg, or 3.0 mg, n=90-95) or to placebo (n=98) administered once a day
      subcutaneously, or orlistat (120 mg, n=95) three times a day orally. All
      individuals had a 500 kcal per day energy-deficit diet and increased their
      physical activity throughout the trial, including the 2-week run-in. Weight
      change analysed by intention to treat was the primary endpoint. An 84-week open
      label extension followed. This study is registered with ClinicalTrials.gov,
      number NCT00422058. FINDINGS: Participants on liraglutide lost significantly more
      weight than did those on placebo (p=0.003 for liraglutide 1.2 mg and p<0.0001 for
      liraglutide 1.8-3.0 mg) and orlistat (p=0.003 for liraglutide 2.4 mg and p<0.0001
      for liraglutide 3.0 mg). Mean weight loss with liraglutide 1.2-3.0 mg was 4.8 kg,
      5.5 kg, 6.3 kg, and 7.2 kg compared with 2.8 kg with placebo and 4.1 kg with
      orlistat, and was 2.1 kg (95% CI 0.6-3.6) to 4.4 kg (2.9-6.0) greater than that
      with placebo. More individuals (76%, n=70) lost more than 5% weight with
      liraglutide 3.0 mg that with placebo (30%, n=29) or orlistat (44%, n=42).
      Liraglutide reduced blood pressure at all doses, and reduced the prevalence of
      prediabetes (84-96% reduction) with 1.8-3.0 mg per day. Nausea and vomiting
      occurred more often in individuals on liraglutide than in those on placebo, but
      adverse events were mainly transient and rarely led to discontinuation of
      treatment. INTERPRETATION: Liraglutide treatment over 20 weeks is well tolerated,
      induces weight loss, improves certain obesity-related risk factors, and reduces
      prediabetes. FUNDING: Novo Nordisk A/S, Bagsvaerd, Denmark.

PMID- 19853908
TI  - Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in
      collagen scaffolds for vascular tissue engineering.
AB  - We investigated the delivery of R136K-CBD (a collagen-binding mutant chimera of
      fibroblast growth factor-1) with a type I collagen scaffold as the delivery
      vehicle to smooth muscle cells (SMCs) for vascular tissue engineering. The
      binding affinity of R136K-CBD to 3-D collagen scaffolds was investigated both in
      the presence and absence of cells and/or salts. 2-D and 3-D visualization of
      delivery of R136K-CBD into SMCs were accomplished by combined fluorescent and
      reflection confocal microscopy. The mitogenic effect of collagen-immobilized
      R136K-CBD on SMCs in 3-D collagen was studied by Cyquant assay at different time
      intervals. In the group devoid of salt and cells, no detectable release of R136K
      CBD into overlying culture media was found, compared with burst-and-continuous
      release of R136K and FGF-1 over a 14-day period in all other groups. The release
      rate of R136K-CBD was 1.7 and 1.6-fold less than R-136K and FGF-1 when media was
      supplemented with 2m salt (P<0.0001), and 2.6 and 2.5-fold less in cell-populated
      collagen hydrogels (P<0.0001), respectively. R136K-CBD showed essentially uniform
      binding to collagen and its distribution was dependent on that of the collagen
      scaffold. Internalization of R136K-CBD into SMCs was documented by confocal
      microscopy. 3-D local delivery of collagen-immobilized R136K-CBD increased the
      proliferation of SMCs in the collagen matrix to significantly greater levels and
      for a significantly greater duration than R136K or FGF-1, with 2.0 and 2.1-fold
      more mitogenicity than R136K and FGF-1 respectively (P<0.0001) at day 7. The
      results suggest that our collagen-binding fusion protein is an effective strategy
      for growth factor delivery for vascular tissue engineering.

PMID- 19853909
TI  - Ring-opening metathesis polymerization-based synthesis of polymeric nanoparticles
      for enhanced tumor imaging in vivo: Synergistic effect of folate-receptor
      targeting and PEGylation.
AB  - We have synthesized amphiphilic copolymers using ring-opening metathesis
      polymerization (ROMP), a copper-catalyzed dipolar click reaction, and osmium
      catalyzed dihydroxylation. The resulting copolymers were easily conjugated with
      folate and dye (indocyanine green) moieties, using a transamidation method. The
      copolymers exhibited high water solubility and formed nanometer-sized self
      assemblies in aqueous medium. The amphiphilic copolymers modified by
      dihydroxylation of the polymer backbone exhibited much lower cmc values than the
      non dihydroxylated copolymer. Copolymers conjugated with folate moieties reduced
      the fluorescence intensity of aqueous polymer solutions both in vitro and in
      vivo, but their self-assemblies efficiently accumulated at tumor sites because of
      folate-receptor recognition at tumor tissue. The PEGylation of copolymers
      improved the stability of the self-assemblies in aqueous medium as well as the
      tumor site selectivity in vivo. Furthermore, the fluorescent nanoparticles
      consisting of PEG- and folate-conjugated ROMP-based copolymers accumulated in
      tumor tissue selectively and efficiently, whereas accumulation in all other
      normal organs was reduced. The PEGylation and folate conjugation can
      synergistically improve the in vivo tumor site selectivity of ROMP-based
      copolymers.

PMID- 19853910
TI  - Signalling pathways involved in the activation of dendritic cells by layered
      double hydroxide nanoparticles.
AB  - Layered double hydroxide (LDH) nanoparticles are attractive as potential drug
      vectors for the targeting not only of tissues, but also of intracellular
      organelles, and particularly the acidic endolysosomes created after cell
      endocytosis. The purpose of this study was to investigate the ability of LDH
      nanoparticles designed as vectors to activate dendritic cells (DCs), as measured
      by various cellular functions. The study also explored the possible signaling
      pathway through which the LDH nanoparticles exerted their effects on the cellular
      functions of DCs. First, LDH nanoparticles with different ratios of Mg(OH)(2) to
      Al(OH)(3) (1:1, 2:1 and 3:1, called R1, R2 and R3 respectively) were optimized
      and had a hydrodynamic diameter of 57 nm with a zeta potential of +35 mV. Then,
      the efficient endocytosis of the optimized LDH nanoparticles by bone marrow
      derived dendritic cells (MDDCs) was monitored by fluorescence-activated cell
      sorting. The effect of R1, R2 and R3 on the expression of the pro- and anti
      inflammatory cytokines (TNF-alpha, IL-6, and IL-12) and the co-stimulatory
      molecules (CD40, CD80, CD86, and MHC class II) in MDDCs was examined. The
      exposure of R1 caused a dose-dependent increase in the expression of TNF-alpha,
      IL-12, CD86 and CD40, while R2 and R3 did not up-regulate these cytokines and co
      stimulatory molecules. Migration assays showed that R1 could increase the
      migration capacity of DCs to CCL21 and up-regulate the expression of CCR7.
      Furthermore, we found that R1 significantly increased the NF-kappaB expression in
      the nucleus (in a dose-dependent manner) and promoted the degradation of total
      IkappaBalpha levels, indicating that the NF-kappaB signaling pathway might
      involve in an R1-induced DC activation. Our results suggested that LDH
      nanoparticles, in the future, may function as a useful vector for ex vivo
      engineering to promote vaccine delivery in immune cells.

PMID- 19853912
TI  - The apoptotic and anti-proliferative activity of Origanum majorana extracts on
      human leukemic cell line.
AB  - Scientists are constantly searching for phytochemicals and compounds with anti
      cancer and antioxidant activity. In this study, the anti-proliferative activity
      of plant extracts from Origanum majorana (marjoram) was tested on human
      lymphoblastic leukemia cell line Jurkat. Cytotoxicity was examined using non
      radioactive cytotoxicity assay and the IC(50) was calculated. At non-cytotoxic
      concentrations, the viability of cells decreased with increase of concentration
      of plant extract. The anti-proliferative effect was also found to be dose
      dependent. Analysis via flow cytometry shows that marjoram extracts stimulated
      apoptosis. Induction of apoptosis was caused by an up-regulation of p53 protein
      levels and down-regulation of Bcl-2alpha. Marjoram exhibited a strong scavenging
      activity (SC(50)=0.03mg dry weight). The conclusions from this study suggest that
      marjoram extracts exhibit anti-proliferative effect and high antioxidant
      activity. For that it merits further investigation as a potential therapeutic
      agent.

PMID- 19853911
TI  - Creation of lysine-deficient mutant lymphotoxin-alpha with receptor selectivity
      by using a phage display system.
AB  - The cytokine lymphotoxin-alpha (LT alpha) activates various biological functions
      through its three receptor subtypes, tumor necrosis factor receptor 1 (TNFR1),
      TNFR2 and herpes virus entry mediator (HVEM), but the relative contribution of
      each receptor to each function is unclear. Therefore it is important to create
      mutant LT alpha with receptor selectivity for optimized cancer therapy and the
      analysis of receptor function. Here, we attempted to create a lysine-deficient
      mutant LT alpha with TNFR1-selective bioactivity using a phage display technique.
      We obtained the TNFR1-selective mutant LT alpha R1selLT, which contained the
      mutations K19N, K28Q, K39S, K84Q, K89V, and K119H. Compared with wild-type LT
      alpha (wtLT alpha), R1selLT showed several-fold higher bioactivity via TNFR1 but
      40-fold lower bioactivity via TNFR2. Kinetic association-dissociation parameters
      of R1selLT with TNFR2 were higher than those of wtLT alpha, whereas these
      parameters of R1selLT with TNFR1 were lower than those of wtLT alpha, suggesting
      that destabilization of the R1selLT-TNFR2 complex causes the decreased
      bioactivity of R1selLT on TNFR2. We also showed that the K84Q mutation
      contributed to the enhanced activity via TNFR1, and K39S lowered activity via
      TNFR2. R1selLT likely will be useful in cancer therapy and in analysis of the LT
      alpha structure-function relationship.

PMID- 19853913
TI  - ID4 methylation predicts high risk of leukemic transformation in patients with
      myelodysplastic syndrome.
AB  - Epigenetic gene silencing due to promoter methylation is observed in human
      cancers like acute myeloid leukemia (AML). Little is known about aberrant
      methylation in myelodysplastic syndrome (MDS), a heterogeneous clonal stem cell
      disorder with a approximately 30% risk of transformation into secondary AML.
      Recent evidence demonstrated that ID4, a negative regulator of transcription, may
      act as a tumor-suppressor gene. To clarify the role of ID4 in MDS, we employed
      methylation-specific PCR (MSP) to examine the methylation status of ID4 in 144
      adult de novo MDS patients. We found that ID4 methylation was present in 35.4%
      (n=51) of these MDS patients and methylaiton was correlated significantly with
      World Health Organization (WHO) subtypes and International Prognostic Scoring
      System (IPSS) risk groups. Patients with advanced stages of WHO subtypes (45.8%
      vs. 21.3%, P=0.002) and higher risk IPSS subgroups (45.7% vs. 26.0%, P=0.014)
      exhibited a significantly higher frequency of ID4 methylation. The median
      survival of patients with ID4 methylation was shorter than patients without ID4
      methylation (12.2 months vs. 26.9 months, P=0.005). Multivariate analysis
      indicated that ID4 methylation status was the independent factor that impacted
      leukemia-free survival (LFS). Disease in patients with ID4 methylation progressed
      more rapidly than those without ID4 methylation (P=0.047, HR=2.11). Our results
      suggest that ID4 may be a therapeutic target in MDS.

PMID- 19853914
TI  - Littoral cell angioma: a correctable cause of progressive pancytopenia in a
      patient with myelodysplastic syndrome.

PMID- 19853915
TI  - The utility and challenges of using ICD codes in child maltreatment research: A
      review of existing literature.
AB  - OBJECTIVE: The objectives of this article are to explore the extent to which the
      International Statistical Classification of Diseases and Related Health Problems
      (ICD) has been used in child abuse research, to describe how the ICD system has
      been applied, and to assess factors affecting the reliability of ICD coded data
      in child abuse research. METHODS: PubMed, CINAHL, PsychInfo and Google Scholar
      were searched for peer reviewed articles written since 1989 that used ICD as the
      classification system to identify cases and research child abuse using health
      databases. Snowballing strategies were also employed by searching the
      bibliographies of retrieved references to identify relevant associated articles.
      The papers identified through the search were independently screened by two
      authors for inclusion, resulting in 47 studies selected for the review. Due to
      heterogeneity of studies meta-analysis was not performed. RESULTS: This paper
      highlights both utility and limitations of ICD coded data. ICD codes have been
      widely used to conduct research into child maltreatment in health data systems.
      The codes appear to be used primarily to determine child maltreatment patterns
      within identified diagnoses or to identify child maltreatment cases for research.
      CONCLUSIONS: A significant impediment to the use of ICD codes in child
      maltreatment research is the under ascertainment of child maltreatment by using
      coded data alone. This is most clearly identified and, to some degree,
      quantified, in research where data linkage is used. PRACTICE IMPLICATIONS: The
      importance of improved child maltreatment identification will assist in
      identifying risk factors and creating programs that can prevent and treat child
      maltreatment and assist in meeting reporting obligations under the CRC.

PMID- 19853916
TI  - The effects of pollution on the vitamins A, E, C, beta-carotene contents and
      oxidative stress of the freshwater crayfish, Astacus leptodactylus.
AB  - In this study, we determined the effects of pollution on levels of antioxidant
      vitamins (A, E, C), beta-carotene and malondialdehyde (MDA), in the
      hepatopancreas and muscle tissues of freshwater crayfish (Astacus leptodactylus).
      The crayfish samples were collected from Aydincik (unpolluted control site) and
      Agin (polluted site) in the Keban Dam Lake (Elazig-Turkey) in August 2007. The
      results showed that the concentrations of vitamins E, C and beta-carotene in both
      tissues were significantly lower, and MDA levels were higher than in controls.
      There were no significant alterations in vitamin A levels. In comparison among
      the sex groups, some values were different significantly between the localities.
      The comparison of same-sex groups of the different localities also showed that
      concentrations of the vitamins E, C, beta-carotene and MDA changed statistically
      according to the tissues between the localities.

PMID- 19853917
TI  - Measuring the performance of police forces in Taiwan using data envelopment
      analysis.
AB  - Recently, the National Police Agency of Taiwan has begun to measure performance
      levels for police forces across the entire island. The performance benchmarks
      resulting from this strategy have become the basis for allocation of government
      funding and other scarce resources. In this work, data envelopment analysis (DEA)
      was used to construct a scalar measure of efficiency for all police precincts.
      Further analyses on the effect of degree of urbanization and possible weight
      restrictions on the outputs upon the efficiency scores of each decision making
      unit (DMU) were conducted. In addition, a three-stage DEA model was applied to
      explicitly incorporate environmental factors into the DEA model. The results show
      that the external environmental factors specified in this study may have some
      effects on the efficiency scores of each district, albeit not statistically
      significant. Most decision making units are technically efficient; the average
      technical efficiency of all DMUs was as high as 98.46% when external
      environmental factors were accounted for.

PMID- 19853918
TI  - Binding site of C-reactive protein on M-ficolin.
AB  - The binding abilities of human C-reactive protein (CRP) with the C-terminal
      fibrinogen-like (FBG) domain and the full-length form of human M-ficolin were
      investigated by pull-down and zonal affinity chromatography analyses. Pull-down
      assays using an N-acetyl-D-glucosamine (GlcNAc)-agarose column demonstrated that
      CRP binds to the trimeric FBG domains, and that the GlcNAc-binding ability of the
      FBG domain is unaffected by CRP binding. Interestingly, the full-length M
      ficolin, comprising the N-terminal collagen-like (COL) and C-terminal FBG
      domains, displayed lower affinity for CRP, and the monomeric FBG domain showed
      virtually no binding to CRP, as qualitatively judged by zonal affinity
      chromatography using a GlcNAc column. These results indicated that CRP binding
      requires the trimeric form of the FBG domain, and that the presence of the COL
      domain reduces the interaction between CRP and M-ficolin. In addition, pull-down
      assays using a histidine-tag affinity column demonstrated that neither the full
      length M-ficolin nor the trimeric FBG domains, immobilized through their C
      terminal histidine tags, showed any affinity for CRP, indicating that the CRP
      binding site is located near Ala326 at the C-terminus of M-ficolin, spatially
      close to a neck region (around Pro115) between the FBG and COL domains. From
      these findings, we concluded that CRP binding is enhanced by conformational
      bending at the neck region of M-ficolin, to avoid steric hindrance by the COL
      domain. Such a situation may be generated by oligomeric M-ficolin binding to
      surfaces with widely distributed ligands, such as pathogens.

PMID- 19853919
TI  - Nucleotide oligomerization domain-2 interacts with 2'-5'-oligoadenylate
      synthetase type 2 and enhances RNase-L function in THP-1 cells.
AB  - Nucleotide-binding and oligomerization domain-2 (NOD2) is an intracellular
      protein involved in innate immunity and linked to chronic inflammatory diseases
      in humans. Further characterization of the full spectrum of proteins capable of
      binding to NOD2 may provide new insights into its normal functioning as well as
      the mechanisms by which mutated forms cause disease. Using a proteomics approach
      to study human THP-1 cells, we have identified 2'-5'-oligoadenylate synthetase
      type 2 (OAS2), a dsRNA binding protein involved in the pathway that activates
      RNase-L, as a new binding partner for NOD2. The interaction was confirmed using
      over-expression of OAS2 and NOD2 in HEK cells. Further confirmation was obtained
      by detecting NOD2 in immunoprecipitates of endogenous OAS2 in THP-1 cells.
      Finally, over-expression of NOD2 in THP-1 cells led to enhanced RNase-L activity
      in cells treated with poly(I:C), a mimic of double-stranded RNA virus infection.
      These data indicate connectivity in pathways involved in innate immunity to
      bacteria and viruses and suggest a regulatory role whereby NOD2 enhances the
      function of RNase-L.

PMID- 19853920
TI  - Variable epitope library-based vaccines: shooting moving targets.
AB  - While the antigenic variability is the major obstacle for developing vaccines
      against antigenically variable pathogens (AVPs) and cancer, this issue is not
      addressed adequately in current vaccine efforts. We developed a novel variable
      epitope library (VEL)-based vaccine strategy using immunogens carrying a mixture
      of thousands of variants of a single epitope. In this proof-of-concept study, we
      used an immunodominant HIV-1-derived CD8+ cytotoxic T-lymphocyte (CTL) epitope as
      a model antigen to construct immunogens in the form of plasmid DNA and
      recombinant M13 bacteriophages. We generated combinatorial libraries expressing
      epitope variants with random amino acid substitutions at 2-5 amino acid positions
      within the epitope. Mice immunized with these immunogens developed epitope
      specific CD8+ IFN-gamma+ T-cell responses that recognized more than 50% of
      heavily mutated variants of wild-type epitope, as demonstrated in T-cell
      proliferation assays and FACS analysis. Strikingly, these potent and broad
      epitope-specific immune responses were long lasting: after 12 months of priming,
      epitope variants were recognized by CD8+ cells and effector memory T cells were
      induced. In addition, we showed, for the first time, the inhibition of T-cell
      responses at the molecular level by immune interference: the mice primed with
      wild-type epitope and 8 or 12 months later immunized with VELs, were not able to
      recognize variant epitopes efficiently. These data may give a mechanistic
      explanation for the failure of recent HIV vaccine trials as well as highlight
      specific hurdles in current molecular vaccine efforts targeting other important
      antigenically variable pathogens and diseases. These findings suggest that the
      VEL-based strategy for immunogen construction can be used as a reliable
      technological platform for the generation of vaccines against AVPs and cancer,
      and contribute to better understanding complex host-pathogen interactions.

PMID- 19853921
TI  - Studies on the formation of a complex of Cu(II) with sodium 1,4-dihydroxy-9,10
      anthraquinone-2-sulphonate - an analogue of the core unit of anthracycline
      anticancer drugs and its interaction with calf thymus DNA.
AB  - Copper(II) forms a complex with sodium 1,4-dihydroxy-9,10-anthraquinone-2
      sulphonate (sodium quinizarin-2-sulphonate, NaQSH(2)), an analogue of the core
      unit of anthracycline antibiotics used in the treatment of cancer. The 1:2 metal
      ligand complex is formed in aqueous solution at neutral and acidic pH while in
      alkaline pH both 1:1 and 1:2 species are formed. The effective stability constant
      of the 1:2 metal-ligand complex is 9.64x10(16) while that of the 1:1 metal-ligand
      complex is 9.4x10(9). The 1:2 complex Cu(NaQSH)(2)(H(2)O)(2) was synthesized and
      characterized by different techniques in solid state and in solution. The complex
      Cu(NaQSH)(2)(H(2)O)(2) interacts with calf thymus DNA which was studied by
      fluorescence spectroscopy. The binding constant and site size for the interaction
      with DNA were determined.

PMID- 19853922
TI  - The impact of staging bipolar disorder on treatment outcome of family
      psychoeducation.
AB  - BACKGROUND: Psychological interventions on top of pharmacological treatment can
      improve the outcome of bipolar disorder. However, there is a paucity of data on
      the aspects that may influence the effectiveness of psychological approaches to
      bipolar disorders. The staging models suggest a progression from prodromal to
      more severe and treatment-resistant presentations. The aim of this study was to
      assess whether a staging model in bipolar disorder was related to patients'
      response to psychoeducation delivered to caregivers. METHODS: Post-hoc analysis
      from a 15-month randomized controlled trial showing the efficacy of group
      psychoeducation for caregivers in the prophylaxis of recurrences. The sample was
      composed of 113 medicated euthymic bipolar outpatients who lived with their
      caregivers. For the purpose of this study the patients were subdivided into two
      groups according to staging. The prophylactic efficacy of caregiver
      psychoeducation was studied based on staging. RESULTS: Patients on Stage I
      benefited from caregiver psychoeducation by having longer time to recurrence (Log
      rank chi-square: 6.26; p=0.012). No significant benefits from caregiver
      psychoeducation were found in patients on advanced stages. LIMITATIONS: The
      present post-hoc analysis was not properly powered to compare each one of the
      four stages with each other, instead staging was divided into Stage I and
      advanced stages (II, III or IV). CONCLUSIONS: Psychoeducation for caregivers of
      bipolar patients on Stage I may improve long-term outcome in terms of time to
      recurrence. This study highlights the need to introduce psychological
      interventions early in the course of the illness as some treatments may be more
      useful in patients at earlier stages of bipolar disorder.

PMID- 19853923
TI  - Chlamydial protease-like activity factor--insights into immunity and vaccine
      development.
AB  - Chlamydia trachomatis is a Gram-negative obligate intracellular pathogen that
      remains the leading cause of bacterial sexually transmitted disease worldwide,
      despite the availability of efficacious antimicrobial therapy. Given that
      chlamydial infections cause severe pathological sequelae in the upper genital
      tract, a licensed vaccine to prevent infection and disease would be an ideal
      solution. Chlamydial protease-like activity factor (CPAF) is a protein secreted
      in considerable amounts into the cytosol of infected cells and released into the
      extracellular milieu upon cellular lysis, which therefore is accessible to the
      host immune system. This is further substantiated by the observation that CPAF is
      immunodominant among other antigens in Chlamydia sero-positive humans. The
      efficacy of vaccination with CPAF against genital chlamydial challenge has been
      evaluated extensively in the murine model. This review will discuss important
      insights into the potential of CPAF as a component of an anti-chlamydial vaccine.

PMID- 19853924
TI  - Development of genetically engineered human sperm immunocontraceptives.
AB  - Contraceptive vaccines targeting sperm are an exciting proposition. This review
      is focused on anti-sperm contraceptive vaccines and genetically engineered human
      antibodies that can be used as immunocontraceptives. Various methods of
      vaccinology and antibody engineering have been used to obtain multi-epitope
      contraceptive vaccines and human single chain variable fragment (scFv) antibodies
      from immunoinfertile and vasectomized men. Contraceptive vaccines comprised of
      various sperm antigens, peptide epitopes or DNA have shown various degrees of
      reversible contraceptive effect in the mouse model and their efficacy is enhanced
      with the multi-epitope combination vaccine. Failure to achieve a complete
      fertility block is probably due to variability in the host immune response. Using
      phage display technology, our laboratory has synthesized in vitro at least four
      novel scFv antibodies with unique complementarity determining regions (CDRs) that
      react with specific fertility-related sperm antigens employing cDNA from
      immunoinfertile and vasectomized men. These antibodies inhibit human sperm
      function in vitro, and their immunocontraceptive effect in vivo is being
      investigated. If these human scFv antibodies block fertility in vivo they may
      provide unique and novel immunocontraceptives, a first-in-kind for human use. The
      multi-epitope contraceptive vaccines and preformed engineered antibodies of
      defined specificity may eliminate concern related to inter-individual variability
      of the immune response.

PMID- 19853925
TI  - Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in
      preeclampsia--a step forward but not the definitive answer.
AB  - Preeclampsia (PE) is a pregnancy-specific syndrome characterized by hypertension,
      proteinuria and edema, which resolves on placental delivery. It is thought to be
      the consequence of impaired placentation due to inadequate trophoblastic invasion
      of the maternal spiral arteries. In PE the maternal plasma concentration of free
      vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) is
      decreased whereas the concentration of soluble fms-like tyrosine kinase-1 (sFlt
      1) and of soluble endoglin (sEng) is increased. These soluble receptors may bind
      VEGF, PLGF and TGFbeta1 and TGFbeta3 in the maternal circulation, causing
      endothelial dysfunction in many maternal tissues. Hence there is a view that the
      pathogenesis is more or less clarified. According to the vascular theory, poor
      placentation leads to poor uteroplacental perfusion and hypoxia, which stimulates
      sFlt-1 and sEng production causing the maternal syndrome. This assumption has
      been recently challenged. The role of hypoxia as the main stimulus for release of
      sFlt-1 has been questioned and the role of inflammatory mechanisms has been
      emphasized. According to this inflammatory theory, poor placentation may
      predispose more to placental oxidative stress than hypoxia and endothelial
      dysfunction may be part of a broader disorder of systemic inflammation. Finally,
      the recent demonstration of activating auto-antibodies to the angiotensin 1
      receptor that experimentally play a major pathogenic role in PE further suggests
      a pleiotropism of aetiologies for this condition. The purpose of this review is
      to critically evaluate the recent hypotheses and their possible insights on early
      diagnosis, prevention and treatment.

PMID- 19853926
TI  - Knocking off the suppressors of cytokine signaling (SOCS): their roles in
      mammalian pregnancy.
AB  - This review discusses the possible role of the suppressor of cytokine signaling
      (SOCS) proteins in mammalian reproduction. SOCS are regulatory proteins that are
      rapidly transcribed in response to intracellular Janus kinase-signal transducer
      and activator of transcription (JAK-STAT) signaling, a cascade governing
      biological functions including cytokine-induced immunological responses and
      reproductive processes. For instance STAT3 appears to mediate trophoblast
      invasion induced by LIF. The SOCS family includes 8 members (cytokine-inducible
      SH2 protein [CIS] and SOCS1-7) that orchestrate distinct reactions by
      antagonizing STAT activation. Emerging evidence points to a role of some family
      members in synchronizing Th1/Th2 cell profiles, the balance in which is
      considered vital to pregnancy maintenance. The reproductive phenotypes of mutant
      mice harboring targeted disruption of SOCS gene isoforms offer insights for
      reproductive immunology, trophoblast function and human pregnancy. CIS transgenic
      mice display impaired responses to IL-2 and resemble STAT5 deficient mice, except
      they are fertile. SOCS1 deficiency leads to an overabundance of IFNgamma
      signaling, yet SOCS1 null mutant mice are able to reproduce. Lack of SOCS3 is
      embryonically lethal due to placental insufficiency, while SOCS3 over-expression
      leads to elevated Th2 responses. SOCS3 seems to be vital for reproduction by
      regulating LIF-driven trophoblast differentiation. SOCS5 inhibits IL-4 signaling,
      yet the SOCS5 transgenic mouse has no conspicuous reproductive phenotype. SOCS-6
      and SOCS-7 null mutant mice display growth retardation. In summary, SOCS proteins
      are avidly involved in fine regulation of immunological and other vital cellular
      responses. Many of the above phenotypes present contradictions to accepted
      reproductive immunological paradigms.

PMID- 19853928
TI  - Sequence analysis, characterization and mRNA distribution of channel catfish
      (Ictalurus punctatus Rafinesque, 1818) chemokine (C-X-C motif) receptor 4 (CXCR4)
      cDNA.
AB  - Chemokine receptor CXCR4, a member of the G protein-coupled receptor superfamily,
      binds selectively CXCL12. This protein plays many important roles in
      immunological as well as pathophysiological functions. In this study, we
      identified and characterized the channel catfish CXCR4 transcript. The full
      length nucleic acid sequence of channel catfish CXCR4 cDNA comprised of 1994
      nucleotides, including an open reading frame, which appears to encode a putative
      peptide of 357 amino acid residues with a calculated molecular mass of 40.1kDa.
      By comparison with the human counterpart, the channel catfish CXCR4 peptide can
      be divided into domains, including seven transmembrane domains, four cytoplasmic
      domains, and four extracellular domains. The CXCR4 transcript was detected in
      spleen, anterior kidney, liver, intestine, skin and gill of all catfish examined
      in this study. Because four CXCL of channel catfish have been identified, the
      result provides valuable information for further exploring the channel catfish
      chemokine signalling pathways and their roles in immune responses to infection.

PMID- 19853929
TI  - Conversion of peripheral CD4(+)CD25(-) T cells to CD4(+)CD25(+) regulatory T
      cells by IFN-gamma in patients with Guillain-Barre syndrome.
AB  - CD4(+)CD25(-) T cells from 25 Guillain-Barre syndrome (GBS) patients were
      stimulated by IFN-gamma to generate the induced CD4(+)CD25(+) regulatory T cells
      (iTregs). Then, their phenotypical and functional characterizations were
      analyzed. Results show that iTregs can be generated from CD4(+)CD25(-) T cells in
      GBS patients by IFN-gamma in the presence of activating anti-CD3 and anti-CD28
      antibodies in vitro. When CD4(+)CD25(-) T cells are stimulated by 40ng/ml IFN
      gamma for 3days, the ratio of conversion is the highest under this condition and
      iTregs are similar to naturally occurring CD4(+)CD25(+) regulatory T cells of
      healthy donors phenotypically and functionally.

PMID- 19853927
TI  - Mucosal immunology of the genital and gastrointestinal tracts and HIV-1
      infection.
AB  - The male and female genital tracts are protected by a local immune system that
      displays features distinguishing them from other mucosal sites. In contrast to
      the intestinal tract, where locally produced IgA is the dominant Ig, secretions
      of the male and female genital tract contain predominantly IgG of both local and
      systemic origin. Genital tract tissues also lack mucosal lymphoepithelial
      inductive sites analogous to intestinal Peyer's patches; consequently, local
      immunization or infections with sexually transmitted pathogens induce low immune
      responses. Human immunodeficiency virus 1 (HIV-1) infection must be primarily
      considered as a mucosal disease with extensive involvement of the systemic immune
      compartment. Although the majority of infections is acquired through the genital
      mucosa, a high rate of virus replication and profound CD4(+) T cell depletion
      occurs in the intestinal mucosa and other mucosal tissues shortly after
      infection. Evaluation of HIV-specific antibodies in sera and external secretions,
      including vaginal washes and semen, unexpectedly revealed a selective lack of IgA
      responses. Moreover, specific antibody-secreting cells in peripheral blood were
      of the IgG isotype, even in mucosally infected individuals. Whether humoral
      responses to previously or newly encountered antigens are compromised in HIV-1
      infected persons is under current investigation.

PMID- 19853930
TI  - Psychological stress and family functioning in mothers of children with allergic
      rhinitis.
AB  - OBJECTIVE: Psychiatric symptoms are observed more commonly in mothers of children
      with allergic disease compared to the general population. In our study, we aimed
      to compare family functioning and anxiety parameters in mothers of children
      diagnosed allergic rhinitis and healthy controls. METHODS: Study group consisted
      of 82 mothers of 7-15 years old children with allergic rhinitis. Control group
      consisted of 70 mothers of children with no chronic diseases. State-Trait Anxiety
      Inventory (STAI) and McMaster Family Assessment Device (FAD) scales was obtained
      from participants. RESULTS: Anxiety scores in mother of children with allergic
      rhinitis were significantly higher than the ones in the control group (50+/-7.54,
      32+/-5.44, p=0.02, respectively). Family assessment scores were higher in mother
      of children with allergic rhinitis when compared to the control group but did not
      reach statistical significance (1.89+/-0.12, 1.87+/-0.95, p=0.19, respectively).
      Smoking status at home and jobless father were found to have a significant impact
      on the evaluation scale in mothers in the case group. CONCLUSION: Psychiatric
      symptoms observed in mothers of children with allergic rhinitis might be
      associated with child disease and the functioning of the entire family rather
      than features of the mother alone. Having a child with allergic rhinitis does not
      affect family functions according to the mother's aspect.

PMID- 19853931
TI  - The impact of chronic suppurative otitis media on children's and teenagers'
      hearing.
AB  - OBJECTIVE: Otitis media is the most common otological condition during childhood
      which compromises sound conduction in the middle ear. In chronic cases, it is
      estimated that the degree to which hearing is compromised is directly
      proportional to the damage caused to the middle ear's structures. It means that
      hearing thresholds may be influenced by factors such as the size and location of
      the tympanic perforation, the presence of ossicular chain erosion or
      disarticulation as well as the presence of cholesteatoma and its growth patterns.
      The goals of this study were to compare air conduction, bone conduction
      thresholds and air-bone gaps of children and teenagers between those with chronic
      suppurative otitis media with cholesteatoma and those without cholesteatoma. To
      compare air-bone gap values for different cholesteatoma growth patterns. To
      verify the relationship between the number of perforated quadrants and the size
      of the air-bone gap. To compare air-bone gap values between tympanic perforations
      in posterior quadrants with those in anterior quadrants. METHODS: A transversal
      study involving 202 children and teenagers (287 ears), aged between 6 and 18,
      with chronic suppurative otitis media with and without cholesteatoma, submitted
      to digital videotoscopy and pure tone audiometry (PTA) was conducted. RESULTS AND
      CONCLUSIONS: Air conduction, bone conduction thresholds and air-bone gaps in
      children and teenagers with CCOM are significantly greater. There were no
      significative differences between air-bone gaps in epitympanic and posterior
      mesotympanic cholesteatomas. In NCCOM, the gap value is positively correlated
      with the number of quadrants with tympanic perforation. There was no
      significative difference between the air-bone gaps in tympanic perforations
      affecting the posterior and anterior quadrants.

PMID- 19853932
TI  - Effects of silver and gold nanoparticles on rainbow trout (Oncorhynchus mykiss)
      hepatocytes.
AB  - The use of nanomaterials is rapidly increasing, while little is known about their
      possible ecotoxicological effects. This work investigates the toxic effects of
      silver (Ag) and gold (Au) nanoparticles on rainbow trout hepatocytes. In addition
      to toxicity assessment the particles were characterized by transmission electron
      microscopy (TEM) and nanoparticle tracking analysis (NTA). Hepatocyte primary
      cultures were exposed to Au and Ag nanoparticles, with and without dissolved
      organic carbon (DOC), as well as HAuCl(4) and AgNO(3) as ionic solutions at
      concentrations up to 17.4mg/L and 19mg/L, respectively. Ag and Au particles were
      within the small nanometer size range when dispersed in pure water. In media with
      higher ionic strength and DOC, particles tended to agglomerate. Cytotoxicity
      assessments showed that Ag nanoparticles caused a significant reduction in
      membrane integrity and cellular metabolic activity in a concentration-dependent
      manner. Au nanoparticles caused a threefold elevation of ROS levels, but no
      cytotoxicity occurred at concentrations tested. The addition of DOC did not alter
      the particles potency of cytotoxicity or ROS induction capacity. The current
      study shows that Ag and Au nanoparticles have adverse effects on rainbow trout
      hepatocytes at low mg/L concentrations.

PMID- 19853934
TI  - Left-ventricular non-compaction with coronary artery disease.
AB  - Left-ventricular non-compaction (LVNC) associated with coronary artery disease
      (CAD) is very rare. We present the case of a 48-year-old man who presented with
      recent anterior wall myocardial infarction and detected to have LVNC
      predominantly involving septum diagnosed by two-dimensional echocardiography. He
      also had significant two-vessel coronary artery disease. To the best of our
      knowledge, this is the first case of LVNC associated with CAD described in the
      literature.

PMID- 19853935
TI  - A distinctly bimodal distribution pattern in the RR interval histogram predicts
      early recurrence of atrial fibrillation after electrical cardioversion.
AB  - Abnormal AV nodal behaviour could contribute to recurrence of Atrial Fibrillation
      (AF) after electrical cardioversion (ECV). We constructed RR interval histograms
      from 24-hour ECGs recorded before ECV in 98 patients with persistent AF. RR
      histograms were classified as unimodal or bimodal, and bimodal histograms
      classified into distinctly or indistinctly bimodal. At 1 week after ECV, 52
      patients (53%) were in AF and at one-month 66 (67%) were in AF. A bimodal RR
      interval distribution during AF was found in 17 patients (18%), a distinctly
      bimodal RR histogram in 8 of these (47%). Compared to those with indistinct
      bimodality, patients with a distinctly bimodal RR histogram were more likely to
      have AF at one-week and one-month (88 vs. 33%, 100 vs. 33%, p=0.01, p=0.009,
      respectively).

PMID- 19853936
TI  - Knowledge and attitudes toward seeking medical care for AMI-symptoms.
AB  - BACKGROUND: Time is crucial when an acute myocardial infarction (AMI) occurs, but
      patients often wait before seeking medical care. AIM: To investigate and compare
      patients' and relatives' knowledge of AMI, attitudes toward seeking medical care,
      and intended behaviour if AMI-symptoms occur. METHODS: The present study was a
      descriptive, multicentre study. Participants were AMI-patients <= 75 years (n =
      364) and relatives to AMI-patients (n = 319). Questionnaires were used to explore
      the participants' knowledge of AMI and attitudes toward seeking medical care.
      RESULTS: Both patients and relatives appeared to act more appropriate to someone
      else's chest pain than to their own. Patients did not have better knowledge of
      AMI-symptoms than relatives. Women would more often contact someone else before
      seeking medical care. A greater percentage of elderly (65-75 years), compared to
      younger individuals, reported that they would call for an ambulance if chest pain
      occurred. CONCLUSIONS: There were only minor differences between patients and
      relatives, regarding both knowledge and attitudes. It seems easier to act
      correctly as a bystander than as a patient. Therefore, in order to decrease
      patients' delay time it is important to educate relatives as well as patients on
      how to respond to symptoms of an AMI.

PMID- 19853937
TI  - CFC1 mutations in Chinese children with congenital heart disease.
AB  - BACKGROUND: Congenital heart disease (CHD) is one of the most common human birth
      defects. Over the last few decades, a variety of CHD-causing gene mutations have
      been identified. The aim of this study was to identify potential pathological
      mutations in the Cryptic (CFC1) gene in 500 Chinese children with CHD and to gain
      insight into the etiology of CHD. METHOD: Sequence analysis of CFC1 in 500 non
      syndromic CHD patients and 250 healthy controls. RESULT: We identified three
      novel non-synonymous variants (c. G506T p. Gly169Val; c. G517A p. Gly173Arg; c.
      G658T p. Leu219Phe). These variants were not observed in 250 controls. All of the
      non-synonymous variants were located in or very close to the hydrophobic C
      terminus. CONCLUSIONS: To our knowledge, this is the first study to suggest that
      CFC1 may be involved in the etiology of non-syndromic CHD in a Chinese
      population.

PMID- 19853938
TI  - Teratocarcinoma-derived growth factor 1 (TDGF1) sequence variants in patients
      with congenital heart defect.
AB  - The goal of our study was to identify potential pathogenic mutations in the TDGF1
      gene in Chinese people with isolated CHD, particularly those with VSD, and to
      provide further insight into the etiology of CHD. A total of 500 CHD Chinese
      patients were investigated for mutations in the TDGF1 gene. Thirteen variants
      were found among the 500 isolated VSD patients and 250 controls, including one
      non-synonymous variant identified in patients but not in controls. This work
      firstly provides human genetic evidence of TDGF1 involved in the pathogenesis of
      VSD, expanding our knowledge of the causative mutations of congenital heart
      defects, in particular, the causative mutations of VSD.

PMID- 19853939
TI  - Driven to drink: Sin taxes near a border.
AB  - This paper investigates household purchasing behavior in response to differing
      alcohol and tobacco taxes near an international border. Our study suggests that
      large tax differentials near borders induce economically important tax avoidance
      behavior, which may limit a government's ability to raise revenue and potentially
      undermine important health and social policy goals. We match novel supermarket
      scanner and consumer expenditure data to measure the size and scope of the effect
      for households and stores. We find that stores near/far from the international
      border have statistically significantly lower/higher sales of beer and tobacco
      than comparable stores far/near the border. Moreover, we find that households
      near the border report higher consumption of these same goods. This is consistent
      with households facing lower prices. Finally, we find measures of externalities
      associated with these goods are higher near the border.

PMID- 19853940
TI  - FTIR microspectroscopy for improved prostate cancer diagnosis.
AB  - Accurate diagnosis and prognosis is essential for cancer management but is
      subject to sampling and inter-observer error. In a recent study, Baker et al.
      compared Fourier transform infrared (FTIR) microspectroscopy with histological
      pathology to evaluate prostate tissue for disease severity. The authors found
      that biochemical changes associated with prostate cancer could be discriminated
      by FTIR to classify confined and locally invasive prostate cancers. These
      findings could enable the development of improved diagnostic and prognostic
      methods for the detection and treatment of prostate cancers.

PMID- 19853941
TI  - Acoustic wave biosensors: physical models and biological applications of quartz
      crystal microbalance.
AB  - Piezoelectric sensors are acoustic sensors that enable the selective and label
      free detection of biological events in real time. These sensors generate acoustic
      waves and utilize measurements of the variation of the wave propagation
      properties as a signal for probing events at the sensor surface. Quartz crystal
      microbalance (QCM) devices, the most widespread acoustic resonators, allow the
      study of viscoelastic properties of matter, the adsorption of molecules, or the
      motility of living cells. In a tutorial-like approach, this review addresses the
      physical principles associated with the QCM, as well as the origin and effects of
      major interfering phenomena. Special attention is paid to the possibilities
      offered by QCM that go beyond microweighing, and important recent examples are
      presented.

PMID- 19853942
TI  - Genetically engineered wheat, redux.

PMID- 19853944
TI  - Tests for determining in-use concentrations of antibiotics and disinfectants are
      based on entirely different concepts: "resistance" has different meanings.
AB  - There are concerns that more extensive application of disinfectants in the food
      industry could result in increased resistance of bacteria to antibiotics and that
      therapeutic failure could ensue. This paper highlights the differences in
      application and mode of action between antibiotics in human or animal medicine
      and disinfectants in the food industry. It describes the completely different
      methods used to determine in-use concentrations in the two contexts. It points
      out that the minimum inhibitory concentration (MIC) is never the concentration at
      which disinfectants should be applied. It also discusses erroneous conclusions
      that may be drawn when the failure of therapy or disinfection is attributed to
      intrinsic properties of the molecules rather than to misuse of antibiotics or
      disinfectants. The paper suggests that the intended meaning of the word
      "resistance" be carefully defined in scientific articles with due reference to
      the measurement mentioned in the abstract and possibly reflected in the title. It
      also suggests that in matters of disinfection the word "resistance" be preferred
      when the phenomenon being studied is killing and "tolerance" when it is the
      adaptation to inhibitory concentrations.

PMID- 19853943
TI  - Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is
      primarily by inhibition of the Raf>MEK>ERK mitogen-activated protein kinase
      cascade and radiosensitization of lapatinib-resistant cells restored by direct
      inhibition of MEK.
AB  - BACKGROUND AND PURPOSE: We recently showed that lapatinib, an EGFR/HER2
      inhibitor, radiosensitized breast cancer cells of the basal and HER2+ subtypes.
      The purpose of this study was to identify the downstream signaling pathways
      responsible for lapatinib-mediated radiosensitization in breast cancer. MATERIALS
      AND METHODS: Response of EGFR downstream signaling pathways was assessed by
      Western blot and clonogenic cell survival assays in breast tumor cells after
      irradiation (5Gy), lapatinib, CI-1040, or combined treatment. RESULTS: In SUM102
      cells, an EGFR+ basal breast cancer cell line, exposure to ionizing radiation
      elicited strong activation of ERK1/2 and JNK, which was blocked by lapatinib, and
      weak/no activation of p38, AKT or STAT3. Direct inhibition of MEK1 with CI-1040
      resulted in 95% inhibition of surviving colonies when combined with radiation
      while inhibition of JNK with SP600125 had no effect. Lapatinib-mediated
      radiosensitization of SUM102 cells was completely abrogated with expression of
      constitutively active Raf. Treatment of lapatinib-resistant SUM185 cells with CI
      1040 restored radiosensitization with 45% fewer surviving colonies when combined
      with radiation. CONCLUSIONS: These data suggest that radiosensitization by
      lapatinib is mediated largely through inhibition of MEK/ERK and that direct
      inhibition of this pathway may provide an additional avenue of radiosensitization
      in EGFR+ or HER2+ breast cancers.

PMID- 19853945
TI  - Comparative analysis of transcriptional and physiological responses of Bacillus
      cereus to organic and inorganic acid shocks.
AB  - Comparative phenotype and transcriptome analyses were performed with Bacillus
      cereus ATCC 14579 exposed to pH 5.5 set with different acidulants including
      hydrochloric acid (HCl), lactic acid (HL) and acetic acid (HAc). Phenotypes
      observed included a decreased growth rate (with HCl), bacteriostatic and
      bactericidal conditions, with 2mM undissociated HAc or HL, and 15mM undissociated
      HAc, respectively. In the latter condition a concomitant decrease in
      intracellular ATP levels was observed. The transcriptome analyses revealed
      general and specific responses to the acidulants used. The general acid stress
      response includes modulation of pyruvate metabolism with activation of the
      butanediol fermentation pathway, and an oxidative stress response that was,
      however, more extensive in the bacteriostatic and bactericidal conditions. HL
      specific and HAc-specific responses include modulation of metabolic pathways for
      amino acid metabolism. Activation of lactate, formate, and ethanol fermentation
      pathways, alternative electron-transport chain components and fatty acid
      biosynthesis genes was noted in the presence of 15mM undissociated HAc. In
      conclusion, our study has provided insights in phenotype-associated, and general
      and acidulant-specific responses in B. cereus.

PMID- 19853946
TI  - Bedside capillary blood glucose measurements in critically ill patients:
      influence of catecholamine therapy.
AB  - OBJECTIVE: To evaluate the effects of catecholamine therapy on the accuracy of
      capillary glucose measurements in hyperglycemic patients. PARTICIPANTS: 43
      hyperglycemic patients older than 18 years admitted to the intensive care unit of
      a tertiary medical center were included from December 2005 to March 2006.
      MEASUREMENTS: This prospective study compares fingerstick and earlobe
      measurements simultaneously to sampled laboratory venous glucose in patients
      treated without (group 1) or with (group 2) catecholamine. Three venous samples
      for serum glucose analysis at three fixed hours and simultaneously two capillary
      glucose determinations were performed during the two first successive days after
      inclusion. A difference between the methods of glucose measurements greater than
      2.3 mmol/l was considered significant. RESULTS: The mean difference between the
      two methods was -0.05 mmol/l in group 1 and +0.29 mmol/l in group 2, while the
      limits of agreement were +4.03 and -4.13 mmol/l and +5.63 and -5.05 mmol/l in
      groups 1 and 2, respectively. A difference between paired measurements greater
      than 2.3 mmol/l was observed in 29% in group 1 and in 40% in group 2 (p=0.038).
      The alternative site did not improve the accuracy. CONCLUSIONS: In critically ill
      patients treated with catecholamine capillary fingerstick blood glucose
      measurement seems inaccurate. Earlobe sampling does not improve accuracy.

PMID- 19853947
TI  - Aspirin for primary prevention of cardiovascular events in patients with
      diabetes: A meta-analysis.
AB  - BACKGROUND: To systematically review trials concerning the benefit and risk of
      aspirin therapy for primary prevention of cardiovascular events in patients with
      diabetes mellitus. METHODS: We searched MEDLINE, EMBASE and the Cochrane Central
      Register of Controlled Trials. Eligible studies were prospective, randomized
      controlled trials of aspirin therapy for primary cardiovascular prevention in
      patients with diabetes with follow-up duration at least 12 months. RESULTS: 7
      trials included 11,618 individuals with diabetes. Aspirin therapy was not
      associated with a statistically significant reduction in major cardiovascular
      events (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83-1.02, p=0.11).
      Aspirin use also did not significantly reduce all-cause mortality (0.95, 95% CI
      0.85-1.06; p=0.33), cardiovascular mortality (0.95, 95% CI 0.71-1.27; p=0.71),
      stroke (0.83, 95% CI 0.63-1.10; p=0.20), or myocardial infarction (MI) (0.85, 95%
      CI 0.65-1.11; p=0.24). There was no significant increased risk of major bleeding
      in aspirin group (2.46, 95% CI 0.70-8.61; p=0.16). Meta-regression suggested that
      aspirin agent could reduce the risk of stroke in women and MI in men.
      CONCLUSIONS: In patients with diabetes, aspirin therapy did not significantly
      reduce the risk of cardiovascular events without an increased risk of major
      bleeding, and showed sex-specific effects on MI and stroke.

PMID- 19853948
TI  - Analysis of continuous patient data from the Czech National Register of patients
      with type 1 and type 2 diabetes using insulin pump therapy.
AB  - AIM: Patient data from the Czech National Register of patients treated with
      Continuous Subcutaneous Insulin Infusion (CSII) were evaluated to compare
      treatment indication, efficacy and safety with specific regard to the type of
      diabetes (T1 vs. T2). METHODS: Evaluation was done on complete data sets of at
      least 3 years from patients with either T1 diabetes (n=730, 93.1%) or T2 diabetes
      (n=54, 6.9%) between 1995 and 2006. RESULTS: HbA(1c) decreased from 9.65 (+/
      0.07) and 9.66 (+/-0.05) for T1 and T2 respectively to 8.24 (+/-0.07) for T1 and
      8.52 (+/-0.27) for T2 after 1 year of treatment, 8.34 (+/-0.07) and 8.54 (+/
      0.26) after 2 years and 8.44 (+/-0.07) and 8.71 (+/-0.25) after 3 years (adjusted
      mean values, +/-SEM). This reduction is significant for both diabetes types.
      Results gathered from the safety analysis revealed almost comparable results for
      both patient groups (rates of adverse events of 42.5 and 34.8 for T1 and T2, per
      100 patients and year). CONCLUSION: Both patient groups achieved substantial
      reduction of HbA(1c). Safety evaluation showed that fewer patients with T2
      diabetes were affected by adverse events. According to that CSII treatment for
      patients with T2 diabetes is similarly effective with a slightly better safety
      profile.

PMID- 19853949
TI  - Oral antiviral therapies are cost-effective vs. no treatment but indirect
      comparisons should be avoided.

PMID- 19853950
TI  - Transarterial therapies in HCC: does embolization increase survival?

PMID- 19853951
TI  - Antiviral therapy for chronic hepatitis B: challenges in Hong Kong.

PMID- 19853952
TI  - A novel model of CCl4-induced cirrhosis with ascites in the mouse.
AB  - BACKGROUND/AIMS: The current approaches to study the molecular mechanisms
      involved in the pathophysiology of liver diseases often rely on the use of
      transgenic mice. However, experimental models of decompensated cirrhosis have not
      been clearly established in mice. Thus, we aimed to set an efficient and well
      tolerated protocol to induce cirrhosis in mice able to progress up to the ascitic
      stage. METHODS: C57BL/6N mice received CCl(4) subcutaneously, intraperitoneally
      or by inhalation. In the latter group, gaseous CCl(4) was administered according
      to three different schedules: increasing exposure times, twice weekly
      (traditional protocol; TP), short inhalation cycles, twice or three times weekly.
      RESULTS: Portal hypertension, sodium retention, and ascites developed in all
      groups between 11 and 15 weeks. Mortality reached 70% in the TP group, but it was
      only 0-10% with all other protocols. All the inhalation groups had significantly
      more ascites at sacrifice than those receiving CCl(4) subcutaneously and
      intraperitoneally. Extensive abdominal adhesions and evidence of enhanced hepatic
      inflammation, as suggested by the increased gene expression of pro-inflammatory
      cytokines in liver tissue, were found in the intraperitoneal group, while large
      granulomas at the injection site and marked neutrophil infiltration of lungs
      developed in the subcutaneous group. No extra-hepatic damage could be detected in
      mice inhaling CCl(4). CONCLUSIONS: The use of short cycles of CCl(4) inhalation
      represents a novel, safe, and effective method to induce decompensated cirrhosis
      in mice. Intraperitoneal CCl(4) leads instead to abdominal adhesions precluding a
      correct evaluation of ascites, while subcutaneous CCl(4) causes an unwanted
      systemic inflammatory response.

PMID- 19853953
TI  - Early prediction of encephalopathy in hospitalized patients with severe acute
      liver disease: the narrow window of opportunity for transplant-free survival.

PMID- 19853954
TI  - Pegylated interferon alpha2b versus pegylated interferon alpha2a for chronic
      hepatitis C: the unreached goal of superiority.

PMID- 19853955
TI  - Absence of viral interference and different susceptibility to interferon between
      hepatitis B virus and hepatitis C virus in human hepatocyte chimeric mice.
AB  - BACKGROUND/AIMS: Both hepatitis B virus (HBV) and hepatitis C virus (HCV)
      replicate in the liver and show resistance against innate immunity and interferon
      (IFN) treatment. Whether there is interference between these two viruses is still
      controversial. We investigated the interference between these two viruses and the
      mode of resistance against IFN. METHODS: We performed infection experiments with
      either or both of the two hepatitis viruses in human hepatocyte chimeric mice.
      Huh7 cell lines with stable production of HBV were also established and
      transfected with HCV JFH1 clone. Mice and cell lines were treated with IFN. The
      viral levels in mice sera and culture supernatants and messenger RNA levels of
      IFN-stimulated genes were measured. RESULTS: No apparent interference between the
      two viruses was seen in vivo. Only a small (0.3 log) reduction in serum HBV and a
      rapid reduction in HCV were observed after IFN treatment, regardless of infection
      with the other virus. In in vitro studies, no interference between the two
      viruses was observed. The effect of IFN on each virus was not affected by the
      presence of the other virus. IFN-induced reductions of viruses in culture
      supernatants were similar to those in in vivo study. CONCLUSIONS: No interference
      between the two hepatitis viruses exists in the liver in the absence of
      hepatitis. The mechanisms of IFN resistance of the two viruses target different
      areas of the IFN system.

PMID- 19853957
TI  - Health problems and retirement due to ill-health among Australian retirees aged
      45-64 years.
AB  - OBJECTIVE: To examine which health problems are associated with retirement due to
      ill-health among Australians aged 45-64 years. METHODS: Cross-sectional analysis
      of self-reported data of 1933 retired men and 3160 retired women aged 45 and
      over, living in NSW in 2008, who took part in the 45 and Up Study. MAIN OUTCOME
      MEASURE: retirement due to ill-health versus retirement for other reasons.
      RESULTS: Among retired women, those who reported ever having been told by a
      doctor that they had thrombosis, depression, osteoarthritis or cancer (except
      melanoma and skin and breast cancer), were twice as likely to have retired early
      due to ill-health as those without these health problems. The number of health
      problems associated with early retirement due to ill-health appeared to be
      slightly greater for men than for women. From most to least significant stroke,
      cancer (except melanoma and skin and prostate cancer), osteoarthritis,
      depression, anxiety and heart disease had significant associations with early
      retirement. In men and women, the strongest association with retirement due to
      ill-health was in self-reported health status. CONCLUSION: Legislators, decision
      makers, and health policymakers should be aware that several health problems are
      associated with early retirement due to ill-health among men and women aged 45-64
      years. Interventions to prevent or treat these health problems would not only
      bring immediate health gains to the individuals themselves but would increase
      their ability to participate in the workforce and/or be otherwise productive in
      society. Interventions would need to be tailored for men and women separately,
      given the gender differences in disease profiles and social roles.

PMID- 19853958
TI  - Increased rate of human mutations where DNA and RNA polymerases collide.
AB  - Gene density and orientation of genes in eukaryotes seem to be correlated with
      the replication origin and the mutation rate is greater in late replicating
      regions; however, the reason for these patterns is unknown. Here, we investigate
      predicted replication origins in the human genome and find that levels of
      polymorphism as well as divergence from the chimpanzee genome are greater in
      genes transcribed on the lagging strand than those on the leading strand. This
      might be caused by interference between RNA and DNA polymerases, and avoidance of
      collisions between these enzymes might be an evolutionary force shaping gene
      orientation and density surrounding replication start sites. Physical constraints
      might have a larger influence on genome evolution than previously thought.

PMID- 19853959
TI  - Thromboxane receptor alpha mediates tumor growth and angiogenesis via induction
      of vascular endothelial growth factor expression in human lung cancer cells.
AB  - The role of thromboxane receptor alpha (TPalpha) in tumor growth and angiogenesis
      was investigated in a nude mice model and in cell culture. Stable human lung
      cancer A549 cells over-expressing TPalpha (A549-TPalpha) was generated and used
      to inoculate athymic nude mice. A549-TPalpha cells induced greater tumor growth
      and increased vascularization in tumors than in the control A549 cells. Increased
      angiogenesis was further verified by studying the induction of vascular
      endothelial growth factor (VEGF) in A549-TPalpha cells. I-BOP, an agonist of TP,
      stimulated the expression of VEGF in this cell line as well as in another human
      lung cancer H157 cells in a time and dose dependent manner. The expression of
      VEGF was determined at both the mRNA and protein levels. The signaling pathways
      that are involved in I-BOP-induced VEGF expression were further examined by the
      use of inhibitors. Inhibition of the extracellular signal-regulated kinase (ERK)
      activation blocked the induction almost completely indicating that ERK activation
      was an essential step in the induction. Each of the three upstream kinases,
      protein kinase A, EGFR kinase and Src kinase, contributed partially to the
      overall induction. However, PI 3-kinase and protein kinase C had minimal
      contribution. These results indicate that activation of the TPalpha induces the
      expression of VEGF through multiple signaling pathways.

PMID- 19853960
TI  - A phase II study of amrubicin, a synthetic 9-aminoanthracycline, in patients with
      previously treated lung cancer.
AB  - PURPOSE: This study was designed to confirm the efficacy and safety of amrubicin,
      a new anthracycline agent, in patients with previously treated non-small cell
      lung cancer (NSCLC) and small cell lung cancer (SCLC). METHODS: Eligible patients
      were required to have recurrent or refractory NSCLC and SCLC after one or two
      previous chemotherapy regimens. All patients received intravenous amrubicin 35
      mg/m(2) on days 1-3 every 3 weeks. Overall response rate (ORR), progression-free
      survival (PFS), and overall survival (OS) were evaluated. RESULTS: Sixty-six
      patients (37 NSCLC and 29 SCLC) were assessable for efficacy and safety
      evaluation. Grade 3 or 4 neutropenia was observed in 39.4% of all patients
      (NSCLC, 37.8%; SCLC, 41.4%). Nonhematological toxicities were mild. No treatment
      related death was observed. The ORRs were 13.5% (95% CI, 4.5-28.8%) in NSCLC and
      44.8% (95% CI, 26.4-64.3%) in SCLC. In SCLC, ORRs were 60.0% in the sensitive
      relapse and 36.8% in the refractory relapse (p=0.2332). In NSCLC, the PFS, OS,
      and 1-year survival were 3.3 months, 12.0 months, and 35.3%, respectively. In
      SCLC, the PFS, OS, and 1-year survival were 4.0 months, 12.0 months, and 46.7%,
      respectively. CONCLUSIONS: Amrubicin is an active and well-tolerated regimen in
      patients with previously treated lung cancer. Amrubicin 35 mg/m(2) seems to
      achieve similar efficacy with less toxicity than amrubicin 40 mg/m(2) in this
      patient population. These results warrant further evaluation in previously
      treated lung cancer.

PMID- 19853961
TI  - Vadose zone attenuation of organic compounds at a crude oil spill site -
      interactions between biogeochemical reactions and multicomponent gas transport.
AB  - Contaminant attenuation processes in the vadose zone of a crude oil spill site
      near Bemidji, MN have been simulated with a reactive transport model that
      includes multicomponent gas transport, solute transport, and the most relevant
      biogeochemical reactions. Dissolution and volatilization of oil components, their
      aerobic and anaerobic degradation coupled with sequential electron acceptor
      consumption, ingress of atmospheric O(2), and the release of CH(4) and CO(2) from
      the smear zone generated by the floating oil were considered. The focus of the
      simulations was to assess the dynamics between biodegradation and gas transport
      processes in the vadose zone, to evaluate the rates and contributions of
      different electron accepting processes towards vadose zone natural attenuation,
      and to provide an estimate of the historical mass loss. Concentration
      distributions of reactive (O(2), CH(4), and CO(2)) and non-reactive (Ar and N(2))
      gases served as key constraints for the model calibration. Simulation results
      confirm that as of 2007, the main degradation pathway can be attributed to
      methanogenic degradation of organic compounds in the smear zone and the vadose
      zone resulting in a contaminant plume dominated by high CH(4) concentrations. In
      accordance with field observations, zones of volatilization and CH(4) generation
      are correlated to slightly elevated total gas pressures and low partial pressures
      of N(2) and Ar, while zones of aerobic CH(4) oxidation are characterized by
      slightly reduced gas pressures and elevated concentrations of N(2) and Ar.
      Diffusion is the most significant transport mechanism for gases in the vadose
      zone; however, the simulations also indicate that, despite very small pressure
      gradients, advection contributes up to 15% towards the net flux of CH(4), and to
      a more limited extent to O(2) ingress. Model calibration strongly suggests that
      transfer of biogenically generated gases from the smear zone provides a major
      control on vadose zone gas distributions and vadose zone carbon balance. Overall,
      the model was successful in capturing the complex interactions between
      biogeochemical reactions and multicomponent gas transport processes. However,
      despite employing a process-based modeling approach, honoring observed parameter
      ranges, and generally obtaining good agreement between field observations and
      model simulations, accurate quantification of natural attenuation rates remains
      difficult. The modeling results are affected by uncertainties regarding gas phase
      saturations, tortuosities, and the magnitude of CH(4) and CO(2) flux from the
      smear zone. These findings highlight the need to better delineate gas fluxes at
      the model boundaries, which will help constrain contaminant degradation rates,
      and ultimately source zone longevity.

PMID- 19853962
TI  - A novel bZIP gene from Tamarix hispida mediates physiological responses to salt
      stress in tobacco plants.
AB  - Basic leucine zipper proteins (bZIPs) are transcription factors that bind
      abscisic acid (ABA)-responsive elements (ABREs) and enable plants to withstand
      adverse environmental conditions. In the present study, a novel bZIP gene,
      ThbZIP1 was cloned from Tamarix hispida. Expression studies in T. hispida showed
      differential regulation of ThbZIP1 in response to treatment with NaCl,
      polyethylene glycol (PEG) 6000, NaHCO(3), and CdCl(2), suggesting that ThbZIP1 is
      involved in abiotic stress responses. To identify the physiological responses
      mediated by ThbZIP1, transgenic tobacco plants overexpressing exogenous ThbZIP1
      were generated. Various physiological parameters related to salt stress were
      measured and compared between transgenic and wild type (WT) plants. Our results
      indicate that overexpression of ThbZIP1 can enhance the activity of both
      peroxidase (POD) and superoxide dismutase (SOD), and increase the content of
      soluble sugars and soluble proteins under salt stress conditions. These results
      suggest that ThbZIP1 contributes to salt tolerance by mediating signaling through
      multiple physiological pathways. Furthermore, ThbZIP1 confers stress tolerance to
      plants by enhancing reactive oxygen species (ROS) scavenging, facilitating the
      accumulation of compatible osmolytes, and inducing and/or enhancing the
      biosynthesis of soluble proteins.

PMID- 19853964
TI  - Metal-tolerant moss Scopelophila cataractae accumulates copper in the cell wall
      pectin of the protonema.
AB  - The growth kinetics in the presence of copper (Cu) of the protonema of the moss
      Scopelophila cataractae and the matrix polysaccharides of its cell walls have
      been analyzed in this study. Protonemal cells cultured in a medium containing
      0.2mM CuSO(4) showed a rapid accumulation of Cu, reaching a maximum between 30
      and 60d at approximately 65 micromolg(-1) DW. Uronic acids were found in similar
      amounts in cell walls of both control and Cu-treated cells, whereas arabinose and
      galactose decreased to 61-67% in the presence of Cu. Cell wall polysaccharides
      were determined after successive extraction with 50mM CDTA, 50mM Na(2)CO(3), 1M
      KOH, and 4M KOH. The pectic fractions (CDTA- and Na(2)CO(3)-soluble) decreased to
      47% and the hemicellulosic fractions (1M KOH- and 4M KOH-soluble) to 86% under Cu
      application. Approximately 43% of the Cu taken into cell walls was released
      following endo-pectate lyase treatment, suggesting that two-fifths of the total
      Cu accumulation was tightly bound to the homogalacturonan of the cell wall
      pectin.

PMID- 19853965
TI  - [Basedow exophthalmos].
AB  - Dysthyroid orbitopathy is a disease that is edematous and inflammatory, generally
      chronic, sometimes subacute or acute, and is characterized by exophthalmos in the
      majority of cases, retraction of the lid, restrictive strabismus with diplopia,
      corneal ulceration, ocular hypertension, and compressive optic neuropathy.
      Proptosis is the cardinal sign. Exophthalmos is frequently axial and is bilateral
      in 85%-90% of cases. Displacement of the globe in the vertical and horizontal
      axes is not rare, particularly when intense enlargement of an extraocular muscle
      produces a mass effect. Proptosis stems from a conflict for the space in the
      orbital cavity. The infiltration of the fat, muscles, and lacrimal gland by
      lymphocytes, plasma cells, and mucopolysaccharides, which are very hydrophilic,
      all contribute to the orbitopathy. The majority of patients with minimal
      exophthalmos do not require special treatment since they tend to improve
      spontaneously. In severe forms, it is important to evaluate the activity for
      steroid use to eliminate the inflammation in the soft tissues and to make
      rehabilitative surgery possible under better conditions. When a good response is
      not obtained, radiotherapy is evaluated. The surgical treatment by bone orbital
      decompression and sometimes lipectomy is indicated in inactive forms, disfiguring
      exophthalmos, certain particular cases such as dysthyroid optic neuropathy,
      ocular hypertension, corneal exposition.

PMID- 19853963
TI  - Comparative proteomic analysis of the short-term responses of rice roots and
      leaves to cadmium.
AB  - Cadmium (Cd) is a non-essential heavy metal that is recognized as a major
      environmental pollutant. While Cd responses and toxicities in some plant species
      have been well established, there are few reports about the effects of short-term
      exposure to Cd on rice, a model monocotyledonous plant, at the proteome level. To
      investigate the effect of Cd in rice, we monitored the influence of Cd exposure
      on root and leaf proteomes. After Cd treatment, root and leaf tissues were
      separately collected and leaf proteins were fractionated with polyethylene
      glycol. Differentially regulated proteins were selected after image analysis and
      identified using MALDI-TOF MS. A total of 36 proteins were up- or down-regulated
      following Cd treatment. As expected, total glutathione levels were significantly
      decreased in Cd-treated roots, and approximately half of the up-regulated
      proteins in roots were involved in responses to oxidative stress. These results
      suggested that prompt antioxidative responses might be necessary for the
      reduction of Cd-induced oxidative stress in roots but not in leaves. In addition,
      RNA gel blot analysis showed that the proteins identified in the proteomic
      analysis were also differentially regulated at the transcriptional level.
      Collectively, our study provides insights into the integrated molecular
      mechanisms of early responses to Cd in rice.

PMID- 19853966
TI  - [Tumoral exophthalmitis].
AB  - Proptosis due to intraorbital tumors is frequent and secondary to several
      etiologies. Generally, young people (0-20 years of age) will be affected mainly
      by benign diseases, such as angiomas or cysts (often dermoid cysts). Yet the
      ophthalmologist must never forget the possibility of rhabdomyosarcoma occurrence
      in a child. Adults (20-60 years of age) will for the most part develop benign
      tumors (cavernous hemangiomas, meningiomas) and inflammatory diseases. Last,
      malignant tumors, such as lymphomas and metastasized tumors, will mainly be
      observed in elderly people over 60 years of age.

PMID- 19853967
TI  - Emergency physician perceptions of patient safety risks.
AB  - STUDY OBJECTIVE: Although national standards to address patient safety exist,
      their relevance to emergency department (ED) patient safety is unclear. We survey
      practicing emergency physicians to assess their perceptions of the relative
      importance of patient safety concerns and how these varied by urban/rural
      location and practice characteristics. METHODS: We developed and analyzed
      electronically collected survey data that assessed emergency physician
      perceptions of patient safety risks. American College of Emergency Physicians
      (ACEP) members rated 16 patient safety concerns with a 5-point Likert scale.
      RESULTS: Of 2,507 emergency physician respondents, 1,114 (44%) practiced in
      urban, 1,056 (42%) in suburban, and 337 (13%) in rural settings. Crowding from
      inpatient boarding (mean Likert scale score 4.3), availability of specialty
      consultation (mean 4.1), and nursing shortages (mean 3.9) were the greatest
      concerns. Rural respondents ranked consultant availability (mean 4.3), lack of
      follow-up after ED care (mean 3.8), and nurse shortages (mean 3.8) as top
      concerns. Crowding was the greatest concern for suburban (mean 4.3) and urban
      emergency physicians (mean 4.5) but was ranked seventh by rural emergency
      physicians (mean 3.5). Crowding was perceived as a greater problem as hospital
      size, ED volume, and the percentage of patients who left without being seen
      increased, regardless of practice location. CONCLUSION: In this sample of
      practicing emergency physicians, rural emergency physicians' patient safety
      concerns differ from those of their urban/suburban counterparts. For
      urban/suburban emergency physicians, crowding is the greatest safety concern; for
      rural emergency physicians, consultant availability was the greatest concern.
      Emergency physicians' greatest concerns are not routinely measured and reported
      as part of national patient safety benchmarking programs.

PMID- 19853968
TI  - Pool chemical blast injury.
AB  - Swimming pools are one of the most popular forms of recreation in the United
      States. Pool-related injuries may produce significant morbidity and mortality,
      and those related to pool chemicals are of particular importance. The majority of
      injuries associated with pool chemicals are respiratory, with the remainder
      composed mainly of dermal exposures. There are few case reports about injuries
      from pool chemicals, and the potential for significant injury from blast force is
      presented here.

PMID- 19853969
TI  - Effect of exclusion policy on the control of outbreaks of suspected viral
      gastroenteritis: Analysis of outbreak investigations in care homes.
AB  - BACKGROUND: Norovirus is an important cause of gastroenteritis outbreaks in care
      homes. Differences exist in the recommended duration of exclusion for affected
      staff during an outbreak. METHODS: We conducted a retrospective analysis of
      outbreak reports in 2006 and 2007 managed by health protection staff in 2
      counties with differing exclusion policies, one advising exclusion of affected
      staff and isolation of residents for 72 hours and the other for 48 hours after
      the resolution of symptoms. We compared attack rates and average numbers of cases
      in residents and staff, adjusting for type of care home and staffing rate.
      RESULTS: A total of 96 outbreaks were managed, 63 with a 72-hour exclusion policy
      and 33 with a 48-hour exclusion policy. The longer exclusion policy resulted in
      lower mean number of cases among staff (6.5 vs 9.6; P=.044) and a lower overall
      attack rate (32.6% vs 35.1%; P=.05). No differences in the mean number of cases
      or the attack rate among residents were seen. CONCLUSION: This brief study
      suggests that a longer exclusion policy reduces the number of cases among staff
      affected with viral gastroenteritis, possibly resulting in less staff absences.
      This could have potential benefits, particularly when resources are limited.

PMID- 19853970
TI  - [The treatment of arterial hypertension: evidence of efficacy and conclusions
      that may be drawn].

PMID- 19853971
TI  - [Current considerations on coffee consumption and sport].

PMID- 19853973
TI  - [Costal involvement due to proximity of an unknown pulmonary neoplasm diagnosed
      by SPECT-CT].

PMID- 19853974
TI  - [Validation of the renogram with immediate diuretic stimulus].
AB  - OBJECTIVE: The aim of this study is to determine the diagnostic reliability of
      the renogram with diuretic stimulus simultaneously at the administration of the
      dose, comparing two groups of 59 patients each one (F0 and F+10), to select
      patients for surgery. MATERIAL AND METHODS: This is an retrospective study about
      two groups of 59 patients to whom the diuretic renogram was carried out by
      stimulus (furosemide), by suspicion of ureteropelvic or vesicoureteral
      obstruction, using (99m)Tc-Mercaptoacetylglicine. In the first one, the study was
      conducted applying the diuretic stimulus 600 seconds after the administration of
      the dose of the radiotracer (F+10). In the second one it was carried out
      simultaneously to the administration (F0). For the interpretation there was used
      the visual analysis, the parameters of the curves and the percentage of
      elimination after modification by the severity and micturition. Statistical
      analysis of the information was made. RESULTS: The F+10 renogram shows a
      sensitivity of 96,7%, specificity of 96,1%, positive predictive value of 90,6%,
      and a negative predictive value of 98,6%. The F0 renogram shows a sensitivity of
      95,2%, specificity of 98,9%, positive predictive value of 95,2%, and a negative
      predictive value of 98,9%. CONCLUSION: The performance of renogram by means of
      the administration of diuretic stimulus at the same time as the administration of
      the radiotracer is a useful and comfortable method in paediatric patients, not
      supposing a significant wastage in the parameters of efficiency of the test in
      the patients selection for surgery.

PMID- 19853975
TI  - [Antibiotic use in patients with renal or hepatic failure].
AB  - Renal or hepatic failure implies the need adjust the dosage of antibiotics that
      are eliminated in active form through the kidneys or metabolized through the
      liver. In the first case, the dose should be reduced by 30% for each level of
      renal impairment (moderate and severe). In hepatic failure, there is no general
      rule, and the specific information provided for each antibiotic should be used.
      Hemodialysis clears antibiotics with a low molecular weight, and a reduced
      protein binding and distribution volume. Thus, the dose should be administered
      immediately after the session or a supplementary dose should be provided. When
      the most intensive extrarenal clearance techniques are used, the presence of a
      high volume of distribution is the only guarantee that the antibiotic will not be
      eliminated.

PMID- 19853976
TI  - Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and
      1-acetyl-pyrazolin derivatives of aminobenzothiazole.
AB  - A series of 6-substituted-[3-substituted-prop-2-eneamido]benzothiazole 9-32 and 6
      substituted-2-[(1-acetyl-5-substituted)-2-pyrazolin-3-yl]aminobenzothiazole 33-56
      were synthesized using appropriate synthetic route and evaluated experimentally
      against maximal electroshock test. Selected compounds were evaluated for
      neurotoxicity, hepatotoxicity and behavioral study. The most active compound, 6
      methyl-2-[(1-acetyl-5-(4-chlorophenyl))-2-pyrazolin-3-yl]aminobenzothiazole 52
      exhibited an ED50 of 25.49 micromol/kg, TD50 of 123.87 micromol/kg and high
      protective index (PI) of 4.86 compared to standard drug phenytoin. The 3D-QSAR
      analysis was carried out by PHASE program and a statistically reliable model with
      good predictive power (r2=0.9220, q2=0.8144) was achieved. The 3D-QSAR plots
      illustrated insights into the structure activity relationship of these compounds
      which may aids in the design of potent aminobenzothiazole derivatives as
      anticonvulsant agents.

PMID- 19853977
TI  - Synthesis, characterization and in vitro evaluation of new oxorhenium- and
      oxotechnetium-CCK4 derivatives as molecular imaging agents for CCK2-receptor
      targeting.
AB  - The goal of this study is to design new (99m)Tc-radiolabelled shortened CCK
      derivatives that might be suitable for the molecular imaging of cholecystokinin-2
      receptors (CCK2-R), these receptors being over-expressed in a number of
      neuroendocrine tumors such as medullary thyroid cancer and small-cell lung
      cancer. For this purpose, we designed several modified CCK4 analogs bearing an
      ON(2)S tetradentate chelating agent at the N-terminus, the CCK4 sequence
      representing the minimal peptide sequence that presents nanomolar affinity and
      activity towards the CCK2-R. Four peptide conjugates of general formula
      (Trt)SN(2)OPh-(X)(n)-CCK4 (X=beta-alanine or 6-aminohexanoic acid spacers; n=0,
      2, 4) and their oxorhenium peptide conjugates have been synthesized and
      characterized. In vitro evaluation of these compounds showed a close relationship
      between the nature and the length of the spacer and the corresponding binding
      affinity values. The most promising oxorhenium complex 5-Re exhibited potent CCK2
      receptor agonist properties in promoting the production of inositol phosphate in
      COS-7 cells (EC(50)=5.17nM). Preliminary (99m)Tc-radiolabelling studies with
      peptide conjugates 3 or 5 led exclusively to the corresponding (99m)TcO-complexes
      3-Tc and 5-Tc, which exhibited high resistance towards an excess of cysteine and
      satisfactory stabilities in human serum. To conclude, the promising in vitro
      characteristics of compounds 5-Re, 5-Tc illustrate the feasibility to develop
      stable radiolabelled shortened CCK4 derivatives with a nanomolar CCK2-R affinity.

PMID- 19853978
TI  - The role of p53 in the cellular toxicity by active trans-platinum complexes
      containing isopropylamine and hydroxymethylpyridine.
AB  - Despite some initial research that reported a lack of activity of trans geometry,
      complexes with general formula trans-[PtCl2(L)(L')] exhibit an important
      cytotoxic activity in cisplatin-sensitive and resistant cell lines. Based on the
      proposed mechanism of action for the trans-platinum compounds, they might form
      DNA adducts initiating a DNA-damage response and ultimately ending in the
      activation of the p53 protein. In the present work, we have studied the
      biochemical properties of the trans-[PtCl2(isopropylamine)(L)] complexes (where L
      is 3- or 4-(hydroxymethyl)-pyridine) against several cell lines and the
      relationship between cytotoxicity and the protein p53. Both complexes showed
      different antitumoral properties depending on the presence or absence of protein
      p53 in isogenic colon carcinoma HCT116 cell lines. Cell cycle studies with the
      complexes in these cell lines were performed to investigate their antitumoral
      activity. Apoptosis was observed to be launched from G1 or G2/M accumulations.
      Confocal microscopy showed the different behaviour of isogenic tumoral cell lines
      treated with the trans-platinum complexes. Our data suggest that small
      differences in the carrier ligands could play an important role in the overall
      biological effects. The body of the research regarding structure-activity
      relationships such as the different position of groups in the carrier ligands
      will provide new rational basis for the design of new platinum antitumor drugs.

PMID- 19853979
TI  - [New developments in iron homeostasis].

PMID- 19853980
TI  - Validity of predictive equations for resting energy expenditure in Belgian normal
      weight to morbid obese women.
AB  - BACKGROUND & AIMS: Individual energy requirements of overweight and obese adults
      can often not be measured by indirect calorimetry, mainly due to the time
      consuming procedure and the high costs. To analyze which resting energy
      expenditure (REE) predictive equation is the best alternative for indirect
      calorimetry in Belgian normal weight to morbid obese women. METHODS: Predictive
      equations were included when based on weight, height, gender, age, fat free mass
      and fat mass. REE was measured with indirect calorimetry. Accuracy of equations
      was evaluated by the percentage of subjects predicted within 10% of REE measured,
      the root mean squared prediction error (RMSE) and the mean percentage difference
      (bias) between predicted and measured REE. RESULTS: Twenty-seven predictive
      equations (of which 9 based on FFM) were included. Validation was based on 536 F
      (18-71 year). Most accurate and precise for the Belgian women were the Huang,
      Siervo, Muller (FFM), Harris-Benedict (HB), and the Mifflin equation with 71%,
      71%, 70%, 69%, and 68% accurate predictions, respectively; bias -1.7, -0.5, +1.1,
      +2.2, and -1.8%, RMSE 168, 170, 163, 167, and 173kcal/d. The equations of HB and
      Mifflin are most widely used in clinical practice and both provide accurate
      predictions across a wide range of BMI groups. In an already overweight group the
      underpredicting Mifflin equation might be preferred. Above BMI 45kg/m(2), the
      Siervo equation performed best, while the FAO/WHO/UNU or Schofield equation
      should not be used in this extremely obese group. CONCLUSIONS: In Belgian women,
      the original Harris-Benedict or the Mifflin equation is a reliable tool to
      predict REE across a wide variety of body weight (BMI 18.5-50). Estimations for
      the BMI range between 30 and 40kg/m(2), however, should be improved.

PMID- 19853981
TI  - Comparative evaluation of ten different condylar base fracture osteosynthesis
      techniques.
AB  - The aim of this study on the mandibles of minipigs was to compare the
      biomechanical stability of different methods of osteosynthesis that are used in
      the operative treatment of fractures of the base of the condyle. Ten different
      systems of osteosynthesis were used to fix 164 fractures, which were tested by a
      two-point bending test after repositioning and fixing. This stress test was
      applied in four directions: lateral to medial, anterior to distal, distal to
      anterior, and medial to lateral. The Eckelt lag screw, one or two 2.0mm
      miniplates, one miniplate with bar (KLS Martin), minicompression plates
      (Medicon), zygoma compression plates (Medartis), condylus fracture plates
      (Medartis), square 4-hole plates (KLS Martin), and either one or two resorbable 4
      hole miniplates (Resorb-X, Martin) were used for osteosynthesis. A total of 164
      tests were done using a universal test machine that measured forces until the
      osteosynthesis failed. Advantages in mechanical load capacity were also measured
      for the Eckelt lag screw when force was applied from medial to lateral. Fixation
      with one resorbable miniplate was not functionally stable. Irrespective of the
      direction of force applied, two miniplates were the most stable technique. There
      were pronounced differences depending on the direction of force applied. The
      results suggest that treatment with a single resorbable miniplate is not
      functionally stable.

PMID- 19853982
TI  - Multiple pathways to functional impairment in obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a chronic and debilitating condition that
      is relatively common in both children and adults, and it is associated with a
      wide range of functional impairments. Mental health researchers and practitioners
      have placed considerable attention on OCD over the past two decades, with the
      goal of advancing treatment and understanding its etiology. Until recently, it
      was unknown to what extent this disorder was associated with functional
      impairment. However, recent research shows that the condition has significant
      social and occupational liabilities. This article discusses etiology, common
      symptom presentations (including comorbid and ancillary symptoms), basic OCD
      subtypes, neuropsychological functioning, and the relation these have with
      functional disability in OCD. Recommendations for future research are also
      considered.

PMID- 19853983
TI  - A developmental-contextual approach to understanding mental health and well-being
      in early adulthood.
AB  - There is an increasing awareness of the social and economic burden of untreated
      mental illness. However, the question remains whether the individuals who are not
      identified as having a mental disorder are mentally healthy and socially
      functioning. This study aims to examine the sequence of Keyes's (Keyes, C. L. M.
      (2002). The mental health continuum: from languishing to flourishing in life.
      Journal of Health and Social Behavior, 43, 207-222.) mental health categories
      based on psychological status and well-being, and to identify qualitative
      differences in these categories by developmental-contextual factors and
      concurrent physical health status and social functioning. This study uses data
      from the UK 1958 National Child Development Study. Information was collected on
      the cohort members from childhood to age 33 years. Psychological distress
      (measured using the Malaise Inventory) and well-being (self-efficacy and
      appraisals of life circumstances) were assessed at age 33 years. Multinomial
      (polytomous) logistic regression models were used to examine the effects of
      individual characteristics and social contextual factors from childhood through
      adolescence on cross categorisations of psychological distress and well-being.
      Our findings suggest that there are similar early life predictors for both poor
      psychosocial functioning and mental ill-health. Our results also demonstrated a
      clear gradient of physical health and social functioning across mental health
      categories, even in the absence of mental disorder. Individual and social
      contextual factors in early life appear to offer clues as to why the absence of
      psychological distress does not always imply good mental health or social
      functioning.

PMID- 19853984
TI  - New approaches to researching patient safety.
AB  - This article presents an overview of contemporary research into patient safety.
      The article suggests that patient safety research to date has tended to privilege
      the formal and structural dimensions of safety at the expense of the social and
      affective dimensions of safety. The article previews the research articles
      brought together in this special issue of Social Science & Medicine, paying
      particular attention to the impact of these studies on the field of patient
      safety research generally. The present article summarises this impact in the form
      of the following three patient safety research principles. First, to account for
      whether and how safe and improvement-oriented practice is achieved, research must
      engage with both the predictability and the complexity of the sites and processes
      it seeks to describe, explain and/or impact on. Second, engaging with complexity
      implicates researchers in experiencing it, and this implicates the research
      process and its methodology in a process of sense-making of the practical and
      affective consequences for and with practitioners inhabiting and enacting that
      complexity. Third, besides numerically-based descriptions, abstracted
      explanations and procedural prescriptions, patient safety research evidence must
      encompass experiential data, collaboratively-produced accounts and/or experience
      based designs.

PMID- 19853985
TI  - The risk of return: intimate partner violence in northern Uganda's armed
      conflict.
AB  - The physical and psychological consequences of armed conflict and intimate
      partner violence are well documented. Less research focuses on their intersection
      and the linkages between domestic violence, gender-based discrimination, and the
      structural violence of poverty in armed conflict. This paper describes emerging
      themes from qualitative interviews with young women who have returned from
      abduction into the Lord's Resistance Army in northern Uganda, many of whom were
      forcibly given as "wives" to commanders. Their interviews reveal multiple levels
      of violence that some women experience in war, including physical and sexual
      violence in an armed group, verbal and physical abuse from extended family
      members, and intimate partner violence. Striking is the violence they describe
      after escaping from the rebels, when they are back with their families. The
      interviews point to how abduction into the armed group may exacerbate problems
      but highlight the structural factors that permit and sustain intimate partner
      violence, including gender inequalities, corruption in the police system, and
      devastating poverty. Findings suggest that decreasing household violence will
      depend on the strength of interventions to address all levels, including
      increasing educational and economic opportunities, increasing accountability of
      the criminal justice system, minimizing substance abuse, and improving the coping
      mechanisms of families and individuals exposed to extreme violence.

PMID- 19853986
TI  - Emotional facilitation effect in the picture-word interference task: an ERP
      study.
AB  - In this paper, we aimed to verify the emotional facilitation effect in the
      picture-word interference task using event-related potentials. Twenty-one healthy
      subjects were asked to categorize the emotional valences of pictures accompanied
      by emotionally congruent, either centrally or laterally positioned Chinese words.
      For both the foveal and lateral word presentations, the reaction times were
      faster compared to the picture-only presentation. Compared to the picture-only
      presentation, P200 amplitude increased under the foveal word presentation
      condition and decreased under the lateral word presentation condition, indicating
      that more attentional resources were required when an accompanying word was in
      the center of a picture than when the word was in the lateral position. Latency
      of P300 was shorter in response to picture-word stimuli irrespective of word
      position, indicating that an emotionally congruent word facilitated the emotional
      processing of the target picture, which verified the emotional facilitation
      effect and was consistent with the results in psychology. The late positive
      component was more positive when the picture-word stimuli were more positive,
      which reflected the feature of positivity offset. The findings suggest that the
      time window for an emotional facilitation effect may be limited to processing
      aspects associated with P300 (i.e., affective evaluation).

PMID- 19853987
TI  - Prospective randomized controlled trial of robotic versus open radical cystectomy
      for bladder cancer: perioperative and pathologic results.
AB  - BACKGROUND: In recent years, surgeons have begun to report case series of
      minimally invasive approaches to radical cystectomy, including robotic-assisted
      techniques demonstrating the surgical feasibility of this procedure with the
      potential of lower blood loss and more rapid return of bowel function and
      hospital discharge. Despite these experiences and observations, at this point
      high levels of clinical evidence with regard to the benefits of robotic
      cystectomy are absent, and the current experiences represent case series with
      limited comparisons to historical controls at best. OBJECTIVE: We report our
      results on a prospective randomized trial of open versus robotic-assisted
      laparoscopic radical cystectomy with regard to perioperative outcomes,
      complications, and short-term narcotic usage. DESIGN, SETTING, AND PARTICIPANTS:
      A prospective randomized single-center noninferiority study comparing open versus
      robotic approaches to cystectomy in patients who are candidates for radical
      cystectomy for urothelial carcinoma of the bladder. Of the 41 patients who
      underwent surgery, 21 were randomized to the robotic approach and 20 to the open
      technique. INTERVENTION: Radical cystectomy, bilateral pelvic lymphadenectomy,
      and urinary diversion by either an open approach or by a robotic-assisted
      laparoscopic technique. MEASUREMENTS: The primary end point was lymph node (LN)
      yield with a noninferiority margin of four LNs. Secondary end points included
      demographic characteristics, perioperative outcomes, pathologic results, and
      short-term narcotic use. RESULTS AND LIMITATIONS: On univariate analysis, no
      significant differences were found between the two groups with regard to age,
      sex, body mass index, American Society of Anesthesiologists classification,
      anticoagulation regimen of aspirin, clinical stage, or diversion type.
      Significant differences were noted in operating room time, estimated blood loss,
      time to flatus, time to bowel movement, and use of inpatient morphine sulfate
      equivalents. There was no significant difference in regard to overall
      complication rate or hospital stay. On surgical pathology, in the robotic group
      14 patients had pT2 disease or higher; 3 patients had pT3/T4 disease; and 4
      patients had node-positive disease. In the open group, eight patients had pT2
      disease or higher; five patients had pT3/T4 disease; and seven patients had node
      positive disease. The mean number of LNs removed was 19 in the robotic group
      versus18 in the open group. Potential study limitations include the limited
      clinical and oncologic follow-up and the relatively small and single-institution
      nature of the study. CONCLUSIONS: We present the results of a prospective
      randomized controlled noninferiority study with a primary end point of LN yield,
      demonstrating the robotic approach to be noninferior to the open approach. The
      robotic approach also compares favorably with the open approach in several
      perioperative parameters.

PMID- 19853988
TI  - The expanding role of partial nephrectomy: a critical analysis of indications,
      results, and complications.
AB  - CONTEXT: The gained expertise in the surgical technique of partial nephrectomy
      (PN) with excellent oncologic outcome and reduced morbidity has contributed to
      more frequent use of PN in many centres of reference, and the recent evidence
      favouring PN over radical nephrectomy (RN) in the prevention of chronic kidney
      disease and possibly linking it to a better overall survival (OS) will constitute
      a strong argument for wider use of PN. OBJECTIVE: To objectively analyse the
      advantages of PN over RN and to evaluate the risk-benefit ratio of expanding the
      indications of PN T1b renal cortical tumours. EVIDENCE ACQUISITION: Literature
      searches on English-language publications were performed using the National
      Library of Medicine database. The queries included the keywords partial
      nephrectomy and nephron sparing surgery. Eight hundred four references were
      scrutinised, and 175 publications were identified and reviewed. Sixty-nine
      articles were selected for this review. These references formed the basis for
      this analysis and were selected based on their relevance and the importance of
      their content. EVIDENCE SYNTHESIS: The use of PN has been steadily increasing,
      particularly in tertiary care centres. This trend is now strengthened by evidence
      supporting the role of PN in reducing the risk of chronic kidney disease in
      patients with renal masses < or =4 cm. A wider use of PN for larger tumours,
      granted technical feasibility, is supported by the preliminary evidence,
      suggesting an OS advantage favouring PN over RN. However, the potential for
      selection bias and residual confounding factors may contribute to the observed
      difference. In the carefully selected patients with tumours >4 cm, PN obtained
      equivalent oncologic outcome to that achieved after RN. Although higher morbidity
      rates were seen after PN, the complication type and severity were not
      prohibitive. CONCLUSIONS: The available evidence supports elective PN as the
      standard surgical treatment for renal cortical tumours < or =4 cm. For larger
      tumours, PN has demonstrated feasibility and oncologic safety in the carefully
      selected patient population studied.

PMID- 19853989
TI  - A critical analysis of the actual role of minimally invasive surgery and active
      surveillance for kidney cancer.
AB  - CONTEXT: The incidence of renal cell carcinomas (RCCs) has increased steadily
      most rapidly for small renal masses (SRMs). Paralleling the changing face of RCC
      in the past 2 decades, new, less invasive surgical options have been developed.
      Laparoscopic radical nephrectomy (LRN) is an established procedure for the
      treatment of RCC. Treatment of SRMs includes open partial nephrectomy (OPN),
      laparoscopic partial nephrectomy (LPN), thermal ablation, and active
      surveillance. OBJECTIVE: To present an overview of minimally invasive treatment
      options and data on surveillance for kidney cancer. EVIDENCE ACQUISITION:
      Literature and meeting abstracts were searched using the terms renal cell
      carcinoma, minimally invasive surgery, laparoscopic surgery, thermal ablation,
      surveillance, and robotic surgery. The articles with the highest level of
      evidence were identified with the consensus of all the collaborative authors and
      reviewed. EVIDENCE SYNTHESIS: Renal insufficiency, as measured by the glomerular
      filtration rate, occurs more often after radical nephrectomy than partial
      nephrectomy (PN). OPN and LPN show comparable results in long-term oncologic
      outcomes. The treatment modality for SRMs should therefore be nephron-sparing
      surgery (NSS). In select patients, thermal ablation or active surveillance of
      SRMs is an alternative. CONCLUSIONS: LRN has become the standard of care for most
      organ-confined tumours not amenable to NSS. Amongst NSS options, PN is the
      treatment of choice, yet remains underutilised in the community. Initial data
      during its learning curve revealed that LPN had higher urologic morbidity.
      However, current emerging data indicate that in experienced hands, LPN has
      shorter ischaemia times, a lower complication rate, and equivalent long-term
      oncologic and renal functional outcomes, yet with decreased patient morbidity
      compared to OPN. Robotic partial nephrectomy is being explored at select centres,
      and cryotherapy and radiofrequency ablation are options for carefully selected
      tumours. Active surveillance is an option for selected high-risk patients.
      Percutaneous needle biopsy is likely to gain increasing relevance in the
      management of small renal tumours.

PMID- 19853990
TI  - Re: Michael J. Morris, Daisy Huang, William K. Kelly, et al. Phase 1 trial of
      high-dose exogenous testosterone in patients with castration-resistant metastatic
      prostate. Eur Urol 2009;56:237-44.

PMID- 19853991
TI  - Cloud point extraction combined with electrothermal atomic absorption
      spectrometry for the speciation of antimony(III) and antimony(V) in food
      packaging materials.
AB  - A simple, sensitive method for the speciation of inorganic antimony by cloud
      point extraction combined with electrothermal atomic absorption spectrometry
      (ETAAS) is presented and evaluated. The method based on the fact that formation
      of a hydrophobic complex of antimony(III) with ammonium pyrrolidine
      dithiocarbamate (APDC) at pH 5.0 and subsequently the hydrophobic complex enter
      into surfactant-rich phase, whereas antimony(V) remained in aqueous solutions.
      Antimony(III) in surfactant-rich phase was analyzed by ETAAS after dilution by
      0.2 mL nitric acid in methanol (0.1M), and antimony(V) was calculated by
      subtracting antimony(III) from the total antimony after reducing antimony(V) to
      antimony(III) by l-cysteine. The main factors affecting the cloud point
      extraction, such as pH, concentration of APDC and Triton X-114, equilibrium
      temperature and incubation time, sample volume were investigated in detail. Under
      the optimum conditions, the detection limit (3 sigma) of the proposed method was
      0.02 ng mL(-1) for antimony(III), and the relative standard deviation was 7.8%
      (c=1.0 ng mL(-1), n=7). The proposed method was successfully applied to
      speciation of inorganic antimony in the leaching solutions of different food
      packaging materials with satisfactory results.

PMID- 19853992
TI  - Soil remediation using a coupled process: soil washing with surfactant followed
      by photo-Fenton oxidation.
AB  - In the present work the use of a coupled process, soil washing and photo-Fenton
      oxidation, was investigated for remediation of a soil contaminated with p,p'-DDT
      (DDT) and p,p'-DDE (DDE), and a soil artificially contaminated with diesel. In
      the soil washing experiments, Triton X-100 (TX-100) aqueous solutions were used
      at different concentrations to obtain wastewaters with different compositions.
      Removal efficiencies of 66% (DDT), 80% (DDE) and 100% (diesel) were achieved for
      three sequential washings using a TX-100 solution strength equivalent to 12 times
      the effective critical micelle concentration of the surfactant (12 CMC(eff)). The
      wastewater obtained was then treated using a solar photo-Fenton process. After 6h
      irradiation, 99, 95 and 100% degradation efficiencies were achieved for DDT, DDE
      and diesel, respectively. In all experiments, the concentration of dissolved
      organic carbon decreased by at least 95%, indicating that residual concentration
      of contaminants and/or TX-100 in the wastewater was very low. The co-extraction
      of metals was also evaluated. Among the metals analyzed (Pb, Cr, Ni, Cu, Cd, Mn
      and Co), only Cr and Mn were detected in the wastewater at concentrations above
      the maximum value permitted by current Brazilian legislation. The effective
      removal of contaminants from soil by the TX-100 washing process, together with
      the high degradation efficiency of the solar photo-Fenton process, suggests that
      this procedure could be a useful option for soil remediation.

PMID- 19853993
TI  - Study of sorption processes and FT-IR analysis of arsenate sorbed onto red muds
      (a bauxite ore processing waste).
AB  - In this study we evaluated the arsenate adsorption capacity of red muds (RM),
      wastes tailing from the alumina production, at different pH values (4, 7, and
      10). RM samples were artificially enriched in batch tests with solutions
      containing increasing concentrations of As(V). The pH of the solution
      significantly affected the adsorption, which increased with the decrease of pH.
      Moreover a sequential extraction procedure [H(2)O; (NH(4))(2)SO(4);
      NH(4)H(2)PO(4); NH(4)(+)-oxalate; NH(4)(+)-oxalate+ascorbic acid] was applied to
      RM samples exchanged with arsenate. Using this approach it was shown that low
      concentrations of arsenate sorbed in RM were present as water soluble and
      exchangeable fractions, while NH(4)(+)-oxalate and NH(4)(+)-oxalate+ascorbic acid
      extracted most of the adsorbed arsenate from RM at different pH values. Besides,
      FT-IR spectroscopy was used to better understand the nature of RM surface
      configuration after As(V) sorption. In the FT-IR spectra the presence of As(V)
      species was highlighted by a well resolved band at 865 cm(-1). The intensity and
      broadness of this band increased at the decreasing of pH. This band could be
      related to nu(As-O) vibration of an inner-sphere Al-O-As complex and/or due to As
      O bonds of the adsorbed As(V) species on Fe oxides of RM samples.

PMID- 19853994
TI  - Comparative impact of cadmium on two phenanthrene-degrading bacteria isolated
      from cadmium and phenanthrene co-contaminated soil in China.
AB  - Alcaligenes faecalis strain J08 and Brevundimonas sp. strain X08 were isolated
      from soils co-contaminated by cadmium (Cd) and polycyclic aromatic hydrocarbons
      (PAHs) in Northeast China. The two strains of bacteria were identified by
      phenotypic tests and 16S rDNA. Different Cd treatments (0.01 mM, 0.1mM, 0.5mM)
      showed no significant influence (p>0.05) on the biodegradation of phenanthrene by
      A. faecalis strain J08. Brevundimonas sp. strain X08 also presented no
      significant differences in the biodegradation of phenanthrene in Cd treatments
      (0.01 mM, 0.1mM). The growth of Brevundimonas sp. strain X08 was prohibited
      significantly (p<0.05) by Cd in the concentration of 0.5mM, but the
      biodegradation of phenanthrene in this group was not impaired. The specific
      biodegradation rate of Brevundimonas sp. strain X08 in the 0.5mM Cd group was
      significantly (p<0.05) higher than rates in other Cd treatments (0mM, 0.01 mM,
      0.1mM).

PMID- 19853995
TI  - Isotherms, kinetics and thermodynamic studies of adsorption of Cu2+ from aqueous
      solutions by Mg2+/K+ type orange peel adsorbents.
AB  - Orange peel (OP) was used as raw material to prepare two novel adsorbents: MgOP
      (Mg(2+) type orange peel adsorbent) and KOP (K(+) type orange peel adsorbent).
      FTIR and SEM were used to characterize the adsorbents. Effects of pH,
      solid/liquid ratio, time and metal ion concentration on the Cu(2+) adsorption by
      these two adsorbents were investigated. The isotherms data were analyzed using
      the Langmuir, Freudlich, Temkin and Dubinin-Radushkevich models. Langmuir model
      provides the best correlation for the adsorption of Cu(2+) by both MgOP and KOP,
      and the mono-layer adsorption capacity for Cu(2+) removal by MgOP and KOP are
      40.37 and 59.77 mg/g, respectively. The adsorbed amounts of Cu(2+) increased with
      the increase in contact time and reached equilibrium within 20 min. The kinetics
      data were analyzed using four adsorption kinetic models: the pseudo-first and
      second-order equations, the Elovich equation and intraparticle diffusion
      equation. Results show that the pseudo-second-order equation fits the
      experimental data very well. Thermodynamic studies showed the spontaneous and
      exothermic nature of the adsorption of Cu(2+) by MgOP and KOP.

PMID- 19853996
TI  - A new insight into Fenton and Fenton-like processes for water treatment.
AB  - In this study, two Fenton (Fe(2+)/H(2)O(2)) and Fenton-like (Fe(3+)/H(2)O(2))
      reactions were compared to clarify their roles in phenol degradation under
      varying H(2)O(2) concentrations, iron dosages and pHs, as well as in the presence
      of radical scavenger. The results of this study showed that a Fenton-like
      reaction must proceed concurrently with a classic Fenton reaction, and the
      concurrent Fenton reaction played a major role in the degradation of pollutants.
      For the Fenton-like reaction, some oxidation intermediates of phenolic compounds
      may promote the conversion of Fe(III) to Fe(II) in addition to the uni-molecular
      decomposition of the Fe(III)-hydroperoxy complexes. The results also showed that
      varying H(2)O(2) concentrations exerted identical effects on the two reactions,
      and that phenol degradation in both reactions could be correlated to the
      decomposition of H(2)O(2). At low levels of iron concentration, the Fenton
      reaction appeared to be more efficient than the Fenton-like reaction in terms of
      the phenol degradation and H(2)O(2) decomposition. Additionally, the Fenton
      reaction had an effective pH range of 2.5-6.0, while the Fenton-like reaction was
      limited to a narrow pH range of 2.8-3.8. Although the Fenton-like reaction was
      much slower than that of the Fenton reaction, the overall extent of phenol
      degradation and H(2)O(2) decomposition at the optimal conditions was equivalent.

PMID- 19853997
TI  - SimulaTEM: multislice simulations for general objects.
AB  - In this work we present the program SimulaTEM for the simulation of high
      resolution micrographs and diffraction patterns. This is a program based on the
      multislice approach that does not assume a periodic object. It can calculate
      images from finite objects, from amorphous samples, from crystals, quasicrystals,
      grain boundaries, nanoparticles or arbitrary objects provided the coordinates of
      all the atoms can be supplied.

PMID- 19853998
TI  - Fabrication of ball-shaped atomic force microscope tips by ion-beam-induced
      deposition of platinum on multiwall carbon nanotubes.
AB  - Ball-shaped atomic force microscope (AFM) tips (ball tips) are useful in AFM
      metrology, particularly in critical dimension AFM metrology and in micro
      tribology. However, a systematic fabrication method for nano-scale ball tips has
      not been reported. We report that nano-scale ball tips can be fabricated by ion
      beam-induced deposition (IBID) of Pt at the free end of multiwall carbon
      nanotubes that are attached to AFM tips. Scanning electron microscopy and
      transmission electron microscopy analyses were done on the Pt ball tips produced
      by IBID in this manner, using ranges of Ga ion beam conditions. The Pt ball tips
      produced consisted of aggregated Pt nano-particles and were found to be strong
      enough for AFM imaging.

PMID- 19853999
TI  - A Pan-European evaluation of residential burns camps for children and young
      people.
AB  - INTRODUCTION: Residential camps for children who have experienced a severe burn
      have existed for over 20 years. The idea stemmed from recognition that children
      with burns face additional challenges, both physical and psychological, and
      therefore need long-term psychosocial support away from the acute care setting.
      Whilst individual programmes have published positive evaluation findings, there
      have been no cross-regional evaluations undertaken to date. METHODS: Five
      European burn camp programmes agreed to take part in a cross-regional study to
      assess the benefits as reported by participants. Shared objectives included:
      giving children the opportunity to experience success through overcoming
      challenging activities, enhancing self-esteem and confidence and enabling
      children to share their experiences of having a burn with peers and staff in a
      supportive environment. Each site collected qualitative feedback from children,
      parents and staff using a common framework. Simple Likert scale data were also
      collected. Each site coded responses into themes which were then collated at one
      site. RESULTS: 104 children, 57 parent/carers and 50 staff took part in the cross
      regional evaluation. Children were aged between 5 and 18 years. 98% of children
      reported that they had enjoyed camp, in particular the activities and the sense
      of achievement they brought, along with the ability to gain support and
      friendship from peers and staff. A large proportion felt that they had benefitted
      from having the opportunity to share their experiences of having a burn with
      peers, leaving them feeling less isolated. In addition some comments related to
      boosting confidence and self-esteem and mastering new skills. Parent/carers again
      cited the increase in their child's confidence in self and appearance as key
      benefits of the camps. Staff reports also included the benefits for burn care
      teams by increasing awareness of patient needs and improving multidisciplinary
      team working. DISCUSSION: The study highlighted the generic benefits of burn
      camps by collapsing themes across five different sites. Whilst this minimised the
      localised differences between camps, further research could be used to analyse
      these subtle differences in greater detail. Some consideration was made of the
      language barriers between sites which could have effected the interpretation of
      some of the individual themes. A multi-methodological approach could be used to
      reduce this effect in future.

PMID- 19854000
TI  - Burn prevention programs for children in developing countries require urgent
      attention: a targeted literature review.
AB  - BACKGROUND: Paediatric burns are a significant international public health
      problem. Developing and developed countries report similar challenges regarding
      paediatric burn prevention programs. Paediatric burns requiring healthcare often
      incur significant health and opportunity costs, death or long-term disability.
      This paper reviews international burn prevention strategies, and considers
      implementation of effective prevention strategies in South Africa. REVIEW
      QUESTION: Are there differences between developed and developing countries
      regarding causes and prevalence of paediatric burns, prevention strategies, and
      evidence of effectiveness? REVIEW FRAMEWORK: Implementing effective burn
      prevention strategies in South Africa. METHOD: This systematic literature review
      identified, and narratively synthesized information from studies reporting
      population-based initiatives to prevent paediatric burns. Strategies from
      developing and developed countries were compared. Common strategies were
      identified, and evidence of effectiveness described. FINDINGS: 30 studies were
      included from 16 developed/developing countries, reporting similar prevention
      strategies. Multi-pronged community-based interventions were most effective.
      Common elements comprised raising awareness of how burns occur, how burns can be
      prevented, the speed of sustaining significant injuries, and the short- and long
      term effects of burns. Burn prevention strategies relevant to South Africa were
      provision of education in different formats (written, pictorial and verbal) in
      places frequented by children and parents, monitoring children more closely in
      hazardous areas (e.g. kitchens), and better planning of homes to reduce hazards.
      CONCLUSION: More work is required to establish effective, sustainable community
      wide prevention programs in developed and developing countries. Effective
      paediatric burn prevention programs for South Africa should acknowledge parent
      and child literacy, how and where information is best accessed, the need to adapt
      effective hazard reduction programs to informal settlements, and the importance
      of legislated minimum safe housing standards. This requires significant
      commitment from Government, communities and individuals.

PMID- 19854001
TI  - Attentional orienting toward social stress stimuli predicts increased cortisol
      responsivity to psychosocial stress irrespective of the early socioeconomic
      status.
AB  - The principal aim of the study was to examine how the natural tendency to shift
      attention toward or away from social stress stimuli during a restful state,
      relates to the magnitude of cortisol elicited in response to a stressful context.
      It also assessed whether any relationship that did emerge between attentional
      biases and cortisol responsivity would be associated with the childhood
      socioeconomic status (SES). Twenty-five healthy normal controls rested for 45min
      during which time they completed an adaptation of Posner's attentional orienting
      paradigm comprising social stress words as cues. Immediately following,
      participants were exposed to a public stressful speech task adapted from the
      Trier Social Stress Test (TSST). Results indicated that a rapid attentional
      engagement in the direction of social stress words prior to stress exposure
      related to a pronounced cortisol response to the stress task, while a slow
      attentional engagement toward social stress words was related to a weak cortisol
      response to the stress task. It was also found that fast engagers of social
      stress information displayed lower self-esteem than slow engagers. Groups did not
      differ in terms of their reported past SES. These findings demonstrate that
      attentional biases for social stress stimuli at rest predict the magnitude of
      cortisol likely to be elicited in response to a subsequent stressor. A natural
      tendency to rapidly shift attention toward social stress-related information may
      be the driving force behind cortisol reactivity when handling psychological forms
      of stress, independent of the early SES environment.

PMID- 19854002
TI  - [Nuchal translucency thickness at 11-14 weeks of gestation: French charts and
      equations].
AB  - OBJECTIVES: To construct French reference charts and equations for nuchal
      translucency thickness (NT) using a large sample of fetuses. To compare this new
      reference with previous ones. MATERIALS AND METHODS: The study data were obtained
      from a single large screening center over seven years. Only measurements taken by
      trained and certified (Fetal Medicine Foundation) operators, with crown rump
      length (CRL) between of 45 to 84 mm were used. Multiple pregnancies, abnormal
      karyotype, cystic hygroma or measurements performed by operators performing less
      than 500 examinations over the study period were excluded. Raw centiles were
      computed for each CRL. They were then fitted using a least square regression
      model with high order polynomials. Predicted median values for NT were compared
      to previously published references and the impact of deviation in median NT was
      evaluated. RESULTS: There were 19,198 measurements included for NT modelling. New
      charts and equations for NT centiles calculations are reported. Median values
      were comparable to those reported in other populations. The small discrepancy in
      median NT did not impact on screening efficiency. CONCLUSION: We present new
      French reference charts and equations for NT at first trimester. These may serve
      as a basis for ongoing audit and quality control. Although they were derived from
      a very and unselected sample, they do not show clinically relevant difference as
      compared to existing references. Our results do no support the use or development
      of customized French reference charts and algorithm for first trimester
      screening.

PMID- 19854003
TI  - Distribution of G (VP7) and P (VP4) genotypes of group A bovine rotaviruses from
      Turkish calves with diarrhea, 1997-2008.
AB  - Group A rotaviruses are major enteric pathogens of calves. In order to
      investigate the genetic diversity of bovine rotaviruses (BRVs), a collection of
      53 BRVs, detected from diarrheic calves from several Turkish geographical areas,
      between 1997 and 2008 was analyzed by RT-PCR for specificities of the outer
      capsid proteins VP7 (G type) and VP4 (P type), for the first time. Overall, G6
      was the predominant G type, detected in 40/53 samples (75.4%), while P[11] was
      the predominant P type, detected in 52/53 samples (98.1%). The most common
      VP7/VP4 combinations were G6P[11] (60.3%) and G10P[11] (24.5%). Mixed infections
      were identified in 7/53 samples (13.2%). In the VP7 region the G6P[11] viruses
      were similar to other ones detected worldwide, forming an independent G6 lineage,
      distantly related to the G6 gene of the vaccine G6P[1] strain NCDV (90.1% amino
      acid identity), and suggesting that G6P[11] viruses represent a genetically
      stable BRV strain. The study of G and P type diversity is pivotal to understand
      the efficacy of the existing rotavirus vaccines and to provide the basis of
      future prophylaxis tools against rotaviral diarrhea of calves.

PMID- 19854004
TI  - A socio-psychological investigation into limitations and incentives concerning
      reporting a clinically suspect situation aimed at improving early detection of
      classical swine fever outbreaks.
AB  - The aim of this study was to identify limitations and incentives in reporting
      clinically suspect situations, possibly caused by classical swine fever (CSF), to
      veterinary authorities with the ultimate aim to facilitate early detection of CSF
      outbreaks. Focus group sessions were held with policy makers from the veterinary
      authorities, and representatives of veterinary practitioners and pig farmer
      unions. Personal interviews with a small group of pig farmers and practitioners
      were held to check limitations raised and solutions proposed during the focus
      group sessions. An electronic questionnaire was mailed to pig farmers and
      practitioners to investigate perceptions and attitudes with respect to clinically
      suspect situations possibly caused by CSF. After triangulating the responses of
      veterinary authorities, veterinary practitioners and farmers, six themes emerged
      across all groups: (1) lack of knowledge on the early signs of CSF; (2) guilt,
      shame and prejudice; (3) negative opinion on control measures; (4)
      dissatisfaction with post-reporting procedures; (5) lack of trust in government
      bodies; (6) uncertainty and lack of transparency of reporting procedures. The
      following solutions to facilitate early detection of CSF were put forward: (a)
      development of a clinical decision-support system for vets and farmers, in order
      to get faster diagnosis and detection of CSF; (b) possibility to submit blood
      samples directly to the reference laboratory to exclude CSF in a clinical
      situation with non-specific clinical signs, without isolation of the farm and
      free of charge for the individual farmer; (c) decrease social and economic
      consequences of reporting CSF, for example by improving the public opinion on
      first reports; (d) better schooling of veterinary officers to deal with emotions
      and insecurity of farmers in the process after reporting; (e) better
      communication of rules and regulations, where to report, what will happen next;
      (f) up-to-date website with information and visual material of the clinical signs
      of CSF.

PMID- 19854005
TI  - The effect of tissue degradation on detection of infectious virus and viral RNA
      to diagnose classical swine fever virus.
AB  - A considerable part of tissue samples that are collected for the monitoring of
      classical swine fever (CSF) from the wild boar population or from domestic pigs
      are unsuitable for virus detection using the fluorescent antibody test (FAT) or
      virus isolation (VI), due to tissue degradation. Reverse transcription polymerase
      chain reaction (RT-PCR) has a higher sensitivity than the FAT and VI, and is
      supposed to be less sensitive to sample degradation. Reliable and quantitative
      information on how long viral RNA and infectious virus can be detected in organs
      and which organs are most susceptible to degradation is, however, lacking. In the
      present study we generated survival curves of infectious CSF virus (CSFV) and
      viral RNA in the tonsil, mesenteric lymph node, spleen and kidney, obtained from
      24 pigs infected with a moderately virulent CSFV strain. Tissue samples were
      stored at room temperature and tested by VI and RT-PCR, directly after storage
      and 1, 2, 3, 4, 7, 14 and 21 days later. It was shown that the RT-PCR is not only
      more sensitive than VI on fresh tissue samples, but RT-PCR is also less
      vulnerable to sample degradation. Average half-life values of viral RNA in the
      tissues ranged from 0.95 to 2.55 days, while half-life values of infectious virus
      ranged from 0.21 to 0.31 days. The tonsil and spleen are regarded as the most
      appropriate organs for the detection of infectious virus and viral RNA, not only
      in fresh samples, but also in samples that suffer from tissue degradation.

PMID- 19854006
TI  - Characterisation of virus-specific peripheral blood cell cytokine responses
      following vaccination or infection with classical swine fever viruses.
AB  - Existing live attenuated classical swine fever virus (CSFV) vaccines provide a
      rapid onset of complete protection but pose problems in discriminating infected
      amongst vaccinated animals. With a view to providing additional information on
      the cellular mechanisms that may contribute to protection, which in turn may aid
      the development of the next generation of CSFV vaccines, we explored the kinetics
      of the cytokine responses from peripheral blood cells of pigs vaccinated with an
      attenuated C-strain vaccine strain and/or infected with a recent CSFV isolate.
      Peripheral blood cells were isolated over the course of vaccination/infection and
      stimulated in vitro with C-strain or UK2000/7.1 viruses. Virus-specific responses
      of peripheral blood cells isolated from C-strain vaccinated pigs were dominated
      by the production of IFN-gamma. IFN-gamma production in response to the C-strain
      virus was first detected in vaccinates 9 days post-vaccination and was sustained
      over the period of observation. In contrast, cells from challenge control animals
      did not secrete IFN-gamma in response to stimulation with C-strain or UK2000/7.1
      viruses. Supernatants from UK2000/7.1 infected animals contained significant
      levels of pro-inflammatory cytokines from day 8 post-infection and these
      cytokines were present in both virus and mock stimulated cultures. The results
      suggest that the C-strain virus is a potent inducer of a type-1 T cell response,
      which may play a role in the protection afforded by such vaccines, whereas the
      pro-inflammatory cytokine responses observed in cultures from infected pigs may
      reflect a pathological pro-inflammatory cascade initiated in vivo following the
      replication and spread of CSFV.

PMID- 19854007
TI  - Preventive vaccination contributes to control classical swine fever in wild boar
      (Sus scrofa sp.).
AB  - Over the last 20 years, oral vaccination implementing a live attenuated vaccine
      has been experimented in Europe in order to control classical swine fever (CSF)
      in Wild Boar (Sus scrofa sp.). This has generally led to an enhanced
      seroprevalence and a decreased viroprevalence at the scale of the whole
      vaccinated populations, but no quantitative analysis has demonstrated the
      protective effect of preventive vaccination or intensive baiting. In the present
      paper we conducted a retrospective analysis at the scale of the municipality,
      taking into account the local dynamics and possible covariates of infection to
      test the effect of preventive vaccination and of the baiting effort. To be
      efficient, vaccination was expected to increase seroprevalence above the level
      considered as suitable for preventing disease invasion (40-60%) independently of
      infection, to protect free areas from disease invasion or contribute to control
      subsequent disease intensity and duration. We also hypothesized that a better
      baiting effort would be correlated with an improvement of immunisation and
      disease control. In uninfected municipalities, seroprevalence increased up to 40%
      after 1 year, i.e., three vaccination campaigns. We observed a significant
      protective effect of preventive vaccination, especially within municipalities
      that had been vaccinated at least 1 year before disease emergence and where virus
      detection did not last more than one quarter. On the other hand, we did not
      detect a significant effect of the baiting effort on local seroprevalence or
      disease dynamics, suggesting that the baiting system could be improved. We
      discuss these results regarding the improvement of management measures and
      further research perspective.

PMID- 19854008
TI  - Cytokine mRNA expression profiles in peripheral blood mononuclear cells from
      piglets experimentally co-infected with porcine reproductive and respiratory
      syndrome virus and porcine circovirus type 2.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine
      circovirus type 2 (PCV2) significantly impact the swine industry worldwide. Co
      infections with these viruses are common and several lines of evidence suggest
      that both PRRSV and PCV2 modify host immune responses that facilitate infection.
      This study examined cytokine mRNA expression profiles of peripheral blood
      mononuclear cells (PBMCs) from piglets experimentally co-infected with PRRSV and
      PCV2 to define the influence of co-infection on host immunity. PBMCs from
      infected and control piglets were stimulated with concanavalin A and the IL-2, IL
      4, IL-6, IL-10, IL-12p40, IFN-gamma and TNF-alpha mRNA levels were determined by
      quantitative reverse transcription-polymerase chain reaction (RT-PCR). PBMCs from
      PRRSV/PCV2 co-infected piglets had significantly reduced IL-2, IL-4, IL-6, IL
      12p40 and IFN-gamma and significantly increased TNF-alpha mRNA levels compared to
      those of the piglets infected with either PRRSV or PCV2 alone. The IL-10 mRNA
      levels in all virus-infected groups were significantly up-regulated early during
      infection. These results suggested that co-infection synergistically suppresses T
      helper 1 (Th1)-type and Th2-type cytokine production by PBMCs, indicating that co
      infection likely compromises cell-mediated and humoral immune responses resulting
      in increased severity of the diseases in piglets.

PMID- 19854009
TI  - Explaining risk. A guide for health professionals.

PMID- 19854011
TI  - Poisoning deaths in China: type and prevalence detected at the Tongji Forensic
      Medical Center in Hubei.
AB  - The records of 218 poisoning deaths from a Department of Forensic Medicine in a
      University of China, Tongji Center for Medicolegal Expertise in Hubei (TCMEH),
      from 1999 to 2008 were retrospectively reviewed. The majority (69.7%) of
      fatalities was between the ages of 20 and 49 years, and there was a male
      preponderance (male:female=1.7:1). The most common classes of substances involved
      in fatalities were rodenticide (19.7%), insecticide and herbicide (17.9%), carbon
      monoxide (16.5%), drugs (13.8%) and alcohols (12.4%). Ingestion was the
      predominant route of exposure (65.1%), followed in frequency by inhalation,
      injection and dermal. In vast majority (64.7%), the manner of death was
      accidental; suicidal intent was present in 25.2% of cases, homicide in 3.7%, and
      undetermined 6.4%. When compared to the former reports from the same institution,
      one for 1956-1984 and another for 1983-1999, an increase was found in the
      proportion of deaths due to rodenticides, CO, alcohols and drugs, as well as in
      accidental poisoning deaths. Poisoning deaths due to pesticides remain the major
      public health problem in China. Further regulatory enforcement should be carried
      out by government to restrict and manage the use of pesticides and rodenticides
      which are most toxic to humans.

PMID- 19854010
TI  - Longitudinal associations between depression and functioning in midlife women.
AB  - Associations between depression and impaired functioning are well known and have
      been documented in numerous clinical, primary care and epidemiological studies.
      Reviews of this research have focused on the elderly. Recent studies suggest that
      women become increasingly vulnerable during the menopausal transition to declines
      in physical and role function and increases in depressive symptoms. The purpose
      of the current research is to review the literature since 1966 for studies
      examining the association between depression and physical and psychosocial
      impairment in midlife women. We selected only longitudinal studies that had the
      potential to elucidate the nature of the complex relationship between depression
      and functioning. Results of the review indicate evidence for bi-directional
      associations between depression and functioning in middle-aged women. However,
      the studies are only broadly informative. Most adjusted for only a limited group
      of factors that could be associated with both depression and functioning. None of
      them directly examined potential moderators or mediators of the relationship
      between depression and impaired functioning.

PMID- 19854012
TI  - Measurement of ethyl glucuronide in vitreous humor with liquid chromatography
      mass spectrometry.
AB  - BACKGROUND: It is important to detect alcohol intake in postmortem
      investigations. However it can be difficult to interpret the results of alcohol
      analysis in putrefied corpses. To avoid this difficulty, there have been studies
      on detection of ethyl glucuronide (EtG), a non-oxidative metabolite of ethyl
      alcohol. The aim of this study was investigate EtG levels in vitreous humor (VH),
      a valuable material in postmortem investigations, and to compare VH EtG levels
      with blood and urine EtG levels. METHODS: Blood, urine and VH specimens were
      collected from 110 cases. Twenty-four cases in which ethyl alcohol was detected
      were included in the study. Although ethanol could not be detected, one case was
      added after having positive results of EtG levels in urine and VH as if he was
      claimed that he was an alcoholic and he had taken alcohol when he died but it
      could not be detected after 6 days of hospitalization. Liquid chromatography-mass
      spectrometry was used to investigate EtG in blood, urine and VH specimens from 25
      cases. RESULTS AND CONCLUSION: VH EtG was in measurable amounts in 19 cases (n:
      25). In fact, VH EtG levels ranged from 0.05 to 1.90 mg/L and were below the
      limit of detection (LOD is 0.03 mg/L) in six cases (n: 25). Blood EtG was in
      measurable amounts in 21 cases (n: 25). Blood EtG levels ranged from 0.64 to 5.82
      mg/L and were below the limit of detection (LOD is 0.083 mg/L) in four cases. EtG
      was detected in urine in 17 cases (n: 19). Urine EtG levels ranged from 0.25 to
      623 mg/L and were below the limit of detection (LOD is 0.12 mg/L) in one case.
      There was a significant relation between VH EtG levels and blood and urine EtG
      levels. The results of the study showed that postmortem VH EtG can be measured to
      reveal alcohol intake.

PMID- 19854013
TI  - Behavioral improvement after transplantation of neural precursors derived from
      embryonic stem cells into the globally ischemic brain of adolescent rats.
AB  - PURPOSE: We intended to determine whether transplanted neural precursors, derived
      from mouse embryonic stem (ES) cells, can migrate and differentiate into mature
      neurons and glial cells in damaged brains and improve functional deficits caused
      by global cerebral ischemic injury in adolescent rats. METHODS: Global ischemia
      was induced using the four-vessel occlusion method. ES cells that display
      enhanced expression of yellow fluorescent protein were co-cultured in N2
      supplemented media with PA6 cells that had stromal derived inducing activity.
      Neural precursor cells were directly transplanted bilaterally into hippocampal C3
      areas 2 weeks after induction of global ischemia. Assessments of the Morris water
      maze test at eight weeks and, the Open field activity levels at two, four, six
      and eight weeks after transplantation were carried out according to standard
      methods. RESULTS: From neural precursors, we were able to generate neural
      lineages, including neurons and glial cells in vitro. Eight weeks following
      transplantation, cellular migration as well as generation of neural cells
      including neurons, astrocytes, and oligodendrocytes developed from the grafted ES
      cell-derived neural precursors were observed. Cell-transplanted animals exhibited
      enhanced functional recovery on sensorimotor and behavioral tests, compared to
      vehicle-treated control animals. CONCLUSION: Therefore, transplantation of mouse
      ES cell-derived neural precursor cells shows promise for improving recovery after
      global ischemia in adolescent rats.

PMID- 19854014
TI  - Genetic susceptibility to febrile seizures: case-control association studies.
AB  - OBJECTIVE: A genetic predisposition to febrile seizures (FS) has long been
      recognized. The inheritance appears to be polygenic in small families or sporadic
      cases of FS encountered in daily clinical practice. To determine whether
      candidate genes are responsible for the susceptibility to FS, we have performed
      genetic association studies in FS patients and controls. METHODS: The single
      nucleotide polymorphisms (SNPs) of genes involved in immune response (interleukin
      (IL) 1B), endocannabinoid signaling (CNR1), acid-base balance (SLC4A3, SLC9A1,
      SLC9A3), gap junction channel (CX43), and GABA(A) receptor trafficking (PRIP1)
      were examined in 249 FS patients (186 simple and 63 complex FS) and 225 controls.
      RESULTS: There were no significant differences in the allele frequencies of the
      SNPs between controls and all FS, simple FS, and complex FS patients. When the
      simple FS patients were divided into two groups according to either having
      (familial) or not having a family history of FS in close relatives (sporadic),
      there was a significant association between IL1B -511 SNP and sporadic simple FS
      (p=0.003). CONCLUSIONS: These data suggest that cytokine genes may act as
      enhancers or attenuators of FS susceptibility. Genetic association study may be
      an effective approach to understanding the molecular basis of FS at least in a
      subgroup of patients.

PMID- 19854015
TI  - [Ascites with high protein concentration 2 months after C-section delivery:
      diagnosis using adenosine deaminase analysis combined with iconography].
AB  - We report the case of a 38-year-old woman, born and raised in Congo, in France
      for 7 years, who developed ascites 2 months after delivery by C-section.
      Thrombopenia at 95,000 elements per millimeter cube was diagnosed during her
      pregnancy and her obstetrician initiated a treatment with corticosteroids.
      Analysis of the ascitic fluid showed a high concentration of proteins (55.7 g/l),
      with 2000 elements, 80% of which were lymphocytes, and very high levels of
      adenosine deaminase. Thoracoabdominal tomodensitometry revealed ascites, a
      multinodular spleen, and hyperemia of the peritoneum; but the liver and the lungs
      were normal and no adenoma was identified. Laparoscopy was not performed and the
      suspected diagnosis of peritoneal tuberculosis was confirmed by only one culture
      of ascitic fluid.

PMID- 19854016
TI  - Usefulness of 18F-FDG PET, combined FDG-PET/CT and EUS in diagnosing primary
      pancreatic carcinoma: a meta-analysis.
AB  - The aim was to evaluate the diagnostic value of (18)F-fluorodeoxyglucose-positron
      emission tomography ((18)F-FDG PET), combined (18)F-fluorodeoxyglucose-positron
      emission tomography/computed tomography ((18)F-FDG PET/CT) and endoscopic
      ultrasonography (EUS) in diagnosing patients with pancreatic carcinoma. MEDLINE,
      EMBASE, Cochrane library and some other databases, from January 1966 to April
      2009, were searched for initial studies. All the studies published in English or
      Chinese relating to the diagnostic value of (18)F-FDG PET, PET/CT and EUS for
      patients with pancreatic cancer were collected. Methodological quality was
      assessed. The statistic software called "Meta-Disc 1.4" was used for data
      analysis. RESULTS: 51 studies were included in this meta-analysis. The pooled
      sensitivity estimate for combined PET/CT (90.1%) was significantly higher than
      PET (88.4%) and EUS (81.2%). The pooled specificity estimate for EUS (93.2%) was
      significantly higher than PET (83.1%) and PET/CT (80.1%). The pooled DOR estimate
      for EUS (49.774) was significantly higher than PET (32.778) and PET/CT (27.105).
      SROC curves for PET/CT and EUS showed a little better diagnostic accuracy than
      PET alone. For PET alone, when interpreted the results with knowledge of other
      imaging tests, its sensitivity (89.4%) and specificity (80.1%) were closer to
      PET/CT. For EUS, its diagnostic value decreased in differentiating pancreatic
      cancer for patients with chronic pancreatitis. In conclusion, PET/CT was a high
      sensitive and EUS was a high specific modality in diagnosing patients with
      pancreatic cancer. PET/CT and EUS could play different roles during different
      conditions in diagnosing pancreatic carcinoma.

PMID- 19854017
TI  - Application of phase optimized liquid chromatography to oligopeptide separations.
AB  - Stationary phase optimized liquid chromatography (POPLC) has been applied to the
      separation of oligopeptides. The retention factors and theoretical plate numbers
      of 13 peptides were determined on five different stationary phases. Based on
      these values, an optimal stationary phase composition of 250mm total length
      consisting of 3 segments of 20mm octadecyl silica, 10mm phenyl silica and 220mm
      embedded polar octadecyl silica was calculated by the optimizer software. Good
      agreement between the calculated and experimental chromatograms was observed. In
      order to achieve short analysis time and baseline separation of all peptides
      gradient elution and optimization of the column temperature were performed. The
      optimized mobile phase conditions consisted of (A) acetonitrile and (B) 0.025M
      aqueous sodium phosphate buffer, pH 3.0, operated at 10% A (0-12min) followed by
      10-50% A (12-32min) at a flow rate of 0.5mLmin(-1) and column temperature of 35
      degrees C. Using these conditions all peptides could be separated in less than
      30min with good resolution and peak symmetry.

PMID- 19854018
TI  - Clinical predictors of significant findings on head computed tomographic
      angiography.
AB  - BACKGROUND: Although head computed tomographic angiography (CTA) is a sensitive
      tool for the evaluation of neurological symptoms in the emergency department
      (ED), little is known about which clinical signs predict significant CTA
      findings. OBJECTIVES: To identify clinical factors that predict significant
      findings on head CTA in patients presenting to the ED with neurological
      complaints. METHODS: Retrospective chart review of consecutive adult patients
      undergoing head CTA over a 6-month period in an urban, tertiary care ED with an
      annual volume of 76,000. Significant head CTA findings were defined as clinically
      significant neurological abnormalities undetected by previous imaging studies.
      Demographics, chief complaint, results of the neurological examinations (NE), and
      head non-contrast computed tomography (CT) results were used as predictors of
      significant head CTA. All predictors with a univariate p < 0.2 using Pearson's
      chi-squared were entered stepwise into a multivariable logistic regression
      including odds ratios (OR), with inclusion restricted to p < 0.05. RESULTS: Chart
      review yielded 456 cases; 215 (47%) were male. Mean age was 62 (SD 20) years.
      There were 189 patients (41%) with abnormal CTAs. Multivariable logistic
      regression indicated five variables that predicted a clinically significant CTA:
      abnormal CT (OR 3.72), chief complaint of subarachnoid hemorrhage-type headache
      (OR 2.30), and motor deficit (OR 2.23), visual deficit (OR 2.23), and other focal
      deficit (OR 2.18) on NE. A chief complaint of trauma (OR 0.23) predicted a normal
      CTA. CONCLUSIONS: Specific historical and focal neurological findings are useful
      for predicting clinically significant findings on head CTA.

PMID- 19854019
TI  - Acute internal jugular venous thrombosis from dialysis catheter.

PMID- 19854020
TI  - A key film.

PMID- 19854021
TI  - Emergency medicine in Argentina: a stepwise process to specialty recognition.
AB  - As emergency medicine (EM) has developed as a medical specialty throughout the
      world, each country has followed its own path to official recognition. Despite a
      successful EM model in the United States, some countries, especially those that
      require government approval of new medical specialties, have often found it
      difficult to attain recognition. As of early 2009, Argentina had yet to recognize
      EM as an official specialty, although some regional governments have acknowledged
      the specialty's status. The Argentine Society of EM has taken a number of steps
      and proposed educational paths to EM specialization to convince Argentina's
      political decision-makers that Emergency Medicine is a fundamental step toward a
      modern medical system. Such national recognition would further an already
      thriving EM community and improve the quality of patient care in Argentina. To
      assist colleagues around the world who are pursuing or will pursue this goal,
      this article outlines Argentina's complex and ongoing path to specialty
      recognition.

PMID- 19854022
TI  - Improving the usability of patient information leaflets.
AB  - OBJECTIVE: This study assesses the usability of three patient information
      leaflets and attempts to improve them while complying with the current EU
      regulations. METHODS: Three original leaflets were tested among 154 potential
      users. Every participant answered 15 scenario questions for one of the leaflets.
      The leaflets were subsequently redesigned based on the test results and evidence
      based Document Design principles. The revised texts were tested among 164
      participants. RESULTS: All three original leaflets suffered from usability
      problems, especially problems related to finding relevant information. On
      average, only 75% of the topics could be located. Comprehension of the
      information, once found, was around 90%. The revisions led to better performance.
      Information was found faster and more successful. Comprehension scores were
      higher as well. A follow-up study shows that these findings can be generalized
      over paper formats. CONCLUSION: Although the current EU regulations for patient
      information leaflets do not guarantee leaflet usability, the leaflets can be
      improved somewhat within the regulations. However, further research should
      evaluate the text structure currently imposed on leaflets. PRACTICAL
      IMPLICATIONS: Information leaflets must be written, or rewritten, according to
      Document Design principles. Furthermore, they must be user tested in a rigorous
      way.

PMID- 19854023
TI  - The role of numeracy on client knowledge in BRCA genetic counseling.
AB  - OBJECTIVE: To assess the impact of numeracy and health literacy on client's
      ability to learn information orally communicated during a BRCA 1/2 genetic
      counseling session. METHODS: Fifty-nine videotaped simulated genetic counseling
      sessions were shown to 246 analogue clients (AC) recruited to imagine themselves
      as the client in the genetic counseling session. AC numeracy, genetic literacy,
      state and trait anxiety, and decisional conflict were assessed. The primary
      outcome was AC learning about BRCA 1/2. RESULTS: Health literacy and numeracy
      were moderately correlated, and each independently predicted learning. Higher
      numeracy was associated with higher knowledge scores only among ACs with adequate
      literacy. Decisional conflict was not related to literacy, numeracy, or knowledge
      acquisition. It was, however, inversely related to state anxiety so that the
      higher post-session state anxiety, the lower the AC's decisional conflict.
      CONCLUSION: Numeracy and health literacy are associated with learning of orally
      communicated information during genetic counseling. It appears that numeracy can
      facilitate learning for literate subjects; it does not, however, make any
      difference in learning ability of clients with significant literacy deficits.
      PRACTICE IMPLICATIONS: Numeracy plays an important role in client's ability to
      learn information communicated during medical sessions, especially among clients
      who are otherwise regarded as literate.

PMID- 19854024
TI  - [Management of renal atrophy in hypertensive patients: experience in Lille].
AB  - INTRODUCTION: In the absence of specific treatment, patients with renal vascular
      disease develop renal atrophy. This population frequently has hypertension
      refractory to medical treatment. The patients who may respond to
      revascularization or at the worst to a nephrectomy must be identified to optimize
      their therapeutic management. METHODS: We conducted an observational
      retrospective study of hypertensive patients with unilateral renal atrophy (renal
      height < 9 cm) followed at the Lille University Hospital Center from 1998 to
      2006. Hypertension, renal clearance (by scintigraphy with MAG3), and
      hypersecretion of renin (segmental/selective venous renin samples) were studied.
      We subsequently classified the patients into 3 groups. Medical treatment was
      optimized for all. RESULTS: The mean follow-up period was 1.3+/-0.2 years. Eight
      patients were treated medically (group 1). Endovascular revascularization was
      used to treat the subjects for which atrophic kidney function accounted for more
      than 10% of their total renal function and with stenosis of the renal artery
      (>70%) (group 2, n=19). Those with a small nonfunctional kidney (<10% of total
      renal function) and hypersecretion of renin (ratio>1.5 in relation to the
      contralateral kidney) underwent a nephrectomy (group 3, n=8). The reduction in
      systolic blood pressure (SBP) was 27 mm Hg and diastolic blood pressure (DBP) 14
      mm Hg for the overall study population (p < 0.001), without any significant
      aggravation of renal function. In group 1, the reduction in blood pressure was
      lower, with medical treatment alone; SBP fell by 13 mm Hg and DBP by 4mm Hg
      (p=ns) ; this group had the lowest initial blood pressure. In group 2,
      revascularization made it possible to improve SBP by 26 mm Hg and DBP by 14 mm Hg
      (p < 0.01) without significant impairment of renal function. Group 3 showed the
      most spectacular improvement in blood pressure, with SBP dropping by 40 mm Hg and
      DBP by 19 mm Hg (p=0.016). But it was also in this group that we observed an
      aggravation in the rate of glomerular filtration with a nonsignificant reduction
      of 12.8 mL/min, nonetheless superior to that expected according to the
      preoperative scintigraphy. CONCLUSION: The results of this work underline the
      importance of multidisciplinary management of patients with small ischemic
      kidneys. Preselection of patients in unstable clinical situations (refractory
      hypertension, progressive kidney failure, flash pulmonary edema) by isotopic and
      endocrinal renal evaluation provides a basis for deciding on treatment. The
      existence of a renin ratio >1.5 can identify the patients most likely to respond
      to nephrectomy. The reduction of renal function following nephrectomy must be
      considered in the discussion about treatment. The functional threshold initially
      defined at 10% may be lowered to 5%, to limit this postoperative reduction.

PMID- 19854025
TI  - Regulations governing morphine prescription in Egypt: an urgent need for
      modification.

PMID- 19854026
TI  - A comparison study of adults with intellectual disability and psychiatric
      disorder with and without forensic involvement.
AB  - The current study describes and compares profiles of patients in the same
      specialized hospital program for patients with intellectual disability with and
      without forensic involvement. A retrospective chart review of 78 individuals (39
      forensic and 39 non-forensic) served between 2006 and 2008 was completed. The
      forensic sample was more likely to have a diagnosis of borderline to mild IQ and
      psychotic disorder was more common. Forensic patients were also more likely to
      have previously used drugs or alcohol. Forensic inpatients had significantly
      longer lengths of stay, and were more likely to change residence from admission
      to discharge than the non-forensic inpatients but the GAF scores did not differ
      between the two groups at admission or discharge. Although there are many
      similarities between the two groups, there are also some important differences
      that exist which should be considered in the design of inpatient and outpatient
      mental health and intellectual disability services.

PMID- 19854027
TI  - Psychometric properties of the Children's Scale of Hostility and Aggression:
      Reactive/Proactive (C-SHARP).
AB  - Although often lacking "malice", aggression is fairly common in children with
      intellectual or developmental disability (I/DD). Despite this, there are no
      scales available that are appropriate for an in-depth analysis of aggressive
      behavior in this population. Such scales are needed for the study of aggressive
      behavior, which is a common target symptom in clinical trials. We assessed the
      reliability and validity of the Children's Scale of Hostility and Aggression:
      Reactive/Proactive (C-SHARP), a new aggression scale created for children with
      I/DD. Data are presented from a survey of 365 children with I/DD aged 3-21 years.
      Interrater reliability was very high for the Problem Scale, which characterizes
      type of aggression. Reliability was lower but largely acceptable for the
      Provocation Scale, which assesses motivation. Validity of the Problem Scale was
      supported by expected differences in children with autism, Down syndrome,
      comorbid disruptive behavior disorders (DBDs) and ADHD. The Provocation Scale,
      which categorizes behavior as proactive or reactive, showed expected differences
      in children with DBD, but was less effective in those with ADHD. The C-SHARP
      appears to have fundamentally sound psychometric characteristics, although more
      research is needed.

PMID- 19854028
TI  - Amplitude of low-frequency oscillations in schizophrenia: a resting state fMRI
      study.
AB  - Recently, a great deal of interest has arisen in resting state fMRI as a measure
      of tonic brain function in clinical populations. Most studies have focused on the
      examination of temporal correlation between resting state fMRI low-frequency
      oscillations (LFOs). Studies on the amplitudes of these low-frequency
      oscillations are rarely reported. Here, we used amplitude of low-frequency
      fluctuations (ALFF) and fractional ALFF (fALFF; the relative amplitude that
      resides in the low frequencies) to examine the amplitude of LFO in schizophrenia.
      Twenty-six healthy controls and 29 patients with schizophrenia or schizoaffective
      disorder participated. Our findings show that patients showed reduced low
      frequency amplitude in proportion to the total frequency band investigated (i.e.,
      fALFF) in the lingual gyrus, left cuneus, left insula/superior temporal gyrus,
      and right caudate and increased fALFF in the medial prefrontal cortex and the
      right parahippocampal gyrus. ALFF was reduced in patients in the lingual gyrus,
      cuneus, and precuneus and increased in the left parahippocampal gyrus. These
      results suggest LFO abnormalities in schizophrenia. The implication of these
      abnormalities for schizophrenic symptomatology is further discussed.

PMID- 19854029
TI  - Scarless healing of oral mucosa is characterized by faster resolution of
      inflammation and control of myofibroblast action compared to skin wounds in the
      red Duroc pig model.
AB  - BACKGROUND: Scar formation following skin trauma can have devastating
      consequences causing physiological and psychosocial concerns. Currently, there
      are no accepted predictable treatments to prevent scarring which emphasizes a
      need for a better understanding of the wound healing and scar formation process.
      OBJECTIVES: Previously it was shown that healing of small experimental wounds in
      the oral mucosa of red Duroc pigs results in significantly reduced scar formation
      as compared with equivalent full-thickness skin wounds. In the present study,
      scar formation was assessed in 17 times larger experimental wounds in both oral
      mucosa and skin of the red Duroc pigs. METHODS: Equivalent experimental wounds
      were created in the oral mucosa and dorsal skin of red Duroc pigs, and scar
      formation, localization and abundance of key wound healing cells, transforming
      growth factor-beta (TGF-beta) and phosphorylated Smad3 (pSmad3) were assessed.
      RESULTS: Oral mucosal wounds displayed significantly less clinical and
      histological scar formation than did the corresponding skin wounds. The number of
      macrophages, mast cells, TGF-beta and pSmad3 immunopositive cells was
      significantly reduced in the oral mucosal wounds as compared with skin wounds
      during the maturation stage of the healing process. Although the number of
      myofibroblasts was significantly elevated, the oral mucosal wounds showed
      significantly less contraction than did the skin wounds over time. CONCLUSIONS:
      Earlier resolution of the inflammatory reaction and reduced wound contraction may
      promote scarless oral mucosal wound healing. In addition, scar formation likely
      depends not only on the number of myofibroblasts but also on the extracellular
      environment which regulates their function.

PMID- 19854030
TI  - Cannabinoid self-administration attenuates PCP-induced schizophrenia-like
      symptoms in adult rats.
AB  - Although considerable attention has been paid to the relationship between
      Cannabis use and schizophrenia, there is a significant uncertainty regarding the
      role of Cannabis consumption in the pathoetiology of the disorder. We
      investigated the correlation between voluntary cannabinoid consumption and
      behavioral traits in an animal model of schizophrenia. Male rats were trained to
      intravenously self-administer the cannabinoid CB1 receptor agonist WIN55,212-2
      (WIN; 12.5 microg/kg/infusion) or vehicle; they subsequently received acute or
      chronic-intermittent intraperitoneal administration of the non-competitive N
      methyl-d-aspartate receptor antagonist phencyclidine (PCP; 2.5mg/kg) or saline.
      We report that WIN self-administration attenuates PCP-induced deficits in (i)
      prepulse inhibition (PPI) of the acoustic startle reflex, (ii) cognitive skills,
      and (iii) sociability, suggesting that cannabinoid consumption can ameliorate the
      schizophrenia-like behavioral alterations caused by PCP. A parallel study
      performed in animals receiving WIN on a non-voluntary basis (experimenter-given)
      confirmed an ameliorating effect of cannabinoid administration on the symptoms of
      schizophrenia induced by PCP.

PMID- 19854031
TI  - Enhancement in thermal stability and resistance to denaturants of lipase
      encapsulated in mesoporous silica with alkyltrimethylammonium (CTAB).
AB  - We assembled a highly durable conjugate with both a high-density accumulation and
      a regular array of lipase, by encapsulating it in mesoporous silica (FSM) with
      alkyltrimethylammonium (CTAB) chains on the surface. The activity for hydrolyzing
      esters of the lipase immobilized in mesoporous silica was linearly related to the
      concentration of lipase, whereas that of non-immobilized lipase showed saturation
      due to self-aggregation at a high concentration. The lipase conjugate also had
      increased resistance to heating when stayed in the silica coupling with CTAB. In
      addition, encapsulating the enzyme with FSM coupled CTAB caused the lipase to
      remain stable even in the presence of urea and trypsin, suggesting that the
      encapsulation prevented dissociation and denaturing. This conjugate had much
      higher activity and much higher stability for hydrolyzing esters when compared to
      the native lipase. These results show that FSM provides suitable support for the
      immobilization and dispersion of proteins in mesopores with disintegration of the
      aggregates.

PMID- 19854032
TI  - [Imerslund-Grasbeck syndrome].
AB  - Anemia is a very common symptom encountered in numerous clinical situations in
      pediatrics. Etiologies range from classic iron-deficiency anemia to the more
      particular etiologies. We report on a clinical history where usual symptoms such
      as asthenia, drowsiness and proteinuria provided a rare diagnosis: Imerslund
      Grasbeck syndrome. We discuss the exams to be done with aregenerative macrocytic
      anemia so as not to underestimate these diagnoses, which each require adapted
      treatments.

PMID- 19854033
TI  - [A rare etiology of painful knee in child].

PMID- 19854034
TI  - [Very preterm birth: is maternal anesthesia a risk factor for neonatal intubation
      in the delivery room?].
AB  - OBJECTIVE: To assess the risk of tracheal intubation at birth in very premature
      neonates related to the type of maternal anesthesia in case of elective cesarean.
      POPULATION AND METHODS: All 219 live-born very premature neonates (28-32 weeks of
      gestation), delivered after an elective cesarean in the 27 maternity wards of 2
      French semi-rural neonatal networks. Eighty-three percent (182/219) were
      delivered in level III maternity wards in university hospitals. RESULTS: Of the
      very preterm neonates, 33.3% (73/219) were intubated in the delivery room, either
      for respiratory distress syndrome or a low APGAR score. Very preterm neonates
      delivered after maternal general anesthesia were more often intubated than those
      delivered after spinal anesthesia (48.7% vs 25.2%; OR: 2.8; 95% CI: 1.8-5.1). The
      risk of intubation related to maternal general anesthesia remained statistically
      significant after an adjustment for gestational age, fetal growth retardation,
      respiratory distress syndrome, type of maternity ward, and a propensity score
      that took into account maternal sociodemographic characteristics and the causes
      of very preterm birth (aOR: 3.4; 95% CI: 1.4-8.2). The risk of intubation related
      to general anesthesia was lower after adjusting for the 5-min APGAR score (aOR:
      2.8; 95% CI: 1.0-7.3). CONCLUSION: Very preterm neonates delivered after cesarean
      with general anesthesia require tracheal intubation in the delivery room more
      often than those delivered with spinal anesthesia. This study cannot assess a
      causal link between anesthesia and the need for neonatal intubation. However,
      neonatologists have to be aware of the type of maternal anesthesia because it may
      interfere with the non-invasive ventilation support policy of the very preterm
      neonate.

PMID- 19854035
TI  - Associations of plasma homocysteine level with brachial-ankle pulse wave
      velocity, LDL atherogenicity, and inflammation profile in healthy men.
AB  - AIMS: To investigate the association of plasma total homocysteine (tHcy) with
      arterial stiffness, measured as brachial-ankle pulse wave velocity (baPWV), LDL
      atherogenicity, and inflammation profile in healthy men. METHODS AND RESULTS: In
      this cross-sectional study, 612 healthy men aged 31-79 years were classified into
      quartiles according to plasma tHcy concentration. In the total study population,
      tHcy concentration showed positive correlation with age (r=0.083, P=0.040),
      interleukin (IL)-1beta (r=0.249, P<0.001), TNF-alpha (r=0.150, P<0.001), IL-6
      (r=0.154, P<0.001), oxidized LDL (oxLDL) (r=0.161, P=<0.001), and baPWV (r=0.087,
      P=0.032); and negative correlation with folate (r=-0.353, P<0.001) and vitamin
      B(12) (r=-0.269, P<0.001). In subgroup analysis based on plasma tHcy level, tHcy
      was associated with baPWV in men with high levels of tHcy (>= 13.1MUmol/L, n=153;
      r=0.258, P=0.001), but not in those with low-tHcy (<13.1 MUmol/L, n=459; r=
      0.033, P=0.478). The association between tHcy and baPWV in the high-tHcy group
      remained significant after adjustment for age, BMI, smoking, drinking, folate,
      and vitamin B12. In the high-tHcy group, tHcy level was also positively
      correlated with IL-1beta, TNF-alpha, oxLDL, and blood pressure; and negatively
      correlated with LDL particle size. In addition, baPWV showed negative correlation
      with LDL particle size and positive correlation with oxLDL in the high-tHcy
      group. CONCLUSION: This study shows an association between high levels of plasma
      tHcy and more advanced arterial stiffness, smaller LDL particle size, and higher
      levels of oxLDL and cytokines in men with hyperhomocysteinemia. Enhanced arterial
      stiffness in hyperhomocysteinemia might be attributed, in part, to Hcy-related
      LDL atherogenicity.

PMID- 19854036
TI  - Increased oral nitric oxide in obstructive sleep apnoea.
AB  - BACKGROUND: Hypoxia and snoring-related mechanical trauma contribute to airway
      inflammation in obstructive sleep apnoea (OSA). Increased exhaled nitric oxide
      (FENO), an airway inflammation marker, has been reported in OSA patients. We
      propose the measure of NO in the oral cavity (oNO) as marker of oropharyngeal
      inflammation in OSA. METHODS: We compared oNO and FENO of 39 OSA patients with
      those of 26 mild asthmatics (ASTHMA), 15 patients with chronic rhinitis or
      rhinosinusitis (CRS) and 24 healthy subjects. A special device was used for oNO
      measurement. Apnoea/hypopnoea index (AHI), oxygen desaturation index, mean and
      nadir SaO2 were calculated from the polysomnography. RESULTS: oNO was
      significantly increased in OSA (104.2 95%CI 80.2-135.5ppb) as compared to ASTHMA
      (71.9 95%CI 56.3-91.9ppb; p=0.015), CRS (54.4 95%CI 40.2-73.7ppb; p=0.009) and
      healthy subjects (63.6 95%CI 59-73ppb; p<0.001). oNO was directly related to AHI
      (r=0.466, p=0.003) and to minutes slept with SaO2 <90% (r=0.471, p=0.011) and it
      was inversely related to nadirSaO2 (r=-0.393, p=0.018). FENO was highest in
      asthmatics (40.3 95%CI 32.5-50.1ppb) and only slightly elevated in OSA (23.1
      95%CI 19,8-28.3ppb) and CRS (22.8 95%CI 16.8-32.5ppb). CONCLUSIONS: The finding
      that oral NO is increased in OSA and is related to upper airway obstructive
      episodes and to hypoxemia severity, strengthens the clinical and pathogenic role
      of oral inflammation in OSA.

PMID- 19854037
TI  - Systemic and airway inflammation and the presence of emphysema in patients with
      COPD.
AB  - The aim of this study was to determine the impact of HRCT-confirmed emphysema on
      biomarkers evaluating airway and systemic inflammation in COPD patients. Forty
      nine consecutive male COPD outpatients with stable COPD were divided in two
      groups according to the presence or absence of emphysema on HRCT. Patients
      underwent pulmonary function tests, plus assessment of exercise capacity, body
      composition and quality of life. Biomarkers were measured in serum (CRP,
      interleukin-6, TNF-alpha, leptin, adiponectin, osteocalcin, insulin growth factor
      1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole
      blood (B-type natriuretic peptide). TNF-alpha, 8-isoprostane and pH were
      additionally measured in exhaled breath condensate. Patients with emphysema had
      more severe lung function impairment, lower body-mass index and fat-free mass
      index, and poorer quality of life. Additionally, they presented increased
      systemic oxidative stress and plasma fibrinogen and lower BNP compared to
      patients without emphysema. After proper adjustment for disease severity, all
      differences remained with the exceptions of body-mass index, fat-free mass index
      and BNP. COPD patients with HRCT-confirmed emphysema present increased systemic
      oxidative stress and fibrinogen, suggesting that they may be more prone to the
      systemic consequences of COPD compared to patients without emphysema.

PMID- 19854038
TI  - Utilization of blended fluidized bed combustion (FBC) ash and pulverized coal
      combustion (PCC) fly ash in geopolymer.
AB  - In this paper, synthesis of geopolymer from fluidized bed combustion (FBC) ash
      and pulverized coal combustion (PCC) fly ash was studied in order to effectively
      utilize both ashes. FBC-fly ash and bottom ash were inter-ground to three
      different finenesses. The ashes were mixed with as-received PCC-fly ash in
      various proportions and used as source material for synthesis of geopolymer.
      Sodium silicate (Na(2)SiO(3)) and 10M sodium hydroxide (NaOH) solutions at mass
      ratio of Na(2)SiO(3)/NaOH of 1.5 and curing temperature of 65 degrees C for 48h
      were used for making geopolymer. X-ray diffraction (XRD), scanning electron
      microscopy (SEM), degree of reaction, and thermal gravimetric analysis (TGA) were
      performed on the geopolymer pastes. Compressive strength was also tested on
      geopolymer mortars. The results show that high strength geopolymer mortars of
      35.0-44.0MPa can be produced using mixture of ground FBC ash and as-received PCC
      fly ash. Fine FBC ash is more reactive and results in higher degree of reaction
      and higher strength geopolymer as compared to the use of coarser FBC ash.
      Grinding increases reactivity of ash by means of increasing surface area and the
      amount of reactive phase of the ash. In addition, the packing effect due to fine
      particles also contributed to increase in strength of geopolymers.

PMID- 19854039
TI  - Contribution of individual waste fractions to the environmental impacts from
      landfilling of municipal solid waste.
AB  - A number of LCA-based studies have reported on the environmental performance of
      landfilling of mixed waste, but little is known about the relative contributions
      of individual waste fractions to the overall impact potentials estimated for the
      mixed waste. In this paper, an empirical model has been used to estimate the
      emissions to the environment from landfilling of individual waste fractions. By
      means of the LCA-model EASEWASTE, the emissions estimated have been used to
      quantify how much of the overall impact potential for each impact category is to
      be attributed to the individual waste fractions. Impact potentials are estimated
      for 1 tonne of mixed waste disposed off in a conventional landfill with bottom
      liner, leachate collection and treatment and gas collection and utilization for
      electricity generation. All the environmental aspects are accounted for 100 years
      after disposal and several impact categories have been considered, including
      standard categories, toxicity-related categories and groundwater contamination.
      Amongst the standard and toxicity-related categories, the highest potential
      impact is estimated for human toxicity via soil (HTs; 12 mPE/tonne). This is
      mostly caused by leaching of heavy metals from ashes (e.g. residues from roads
      cleaning and vacuum cleaning bags), batteries, paper and metals. On the other
      hand, substantial net environmental savings are estimated for the categories
      Global Warming (GW; -31 mPE/tonne) and Eco-Toxicity in water chronic (ETwc; -53
      mPE/tonne). These savings are mostly determined by the waste fractions
      characterized by a high content of biogenic carbon (paper, organics, other
      combustible waste). These savings are due to emissions from energy generation
      avoided by landfill gas utilization, and by the storage of biogenic carbon in the
      landfill due to incomplete waste degradation.

PMID- 19854040
TI  - Interval-parameter semi-infinite fuzzy-stochastic mixed-integer programming
      approach for environmental management under multiple uncertainties.
AB  - In this study, an interval-parameter semi-infinite fuzzy-chance-constrained mixed
      integer linear programming (ISIFCIP) approach is developed for supporting long
      term planning of waste-management systems under multiple uncertainties in the
      City of Regina, Canada. The method improves upon the existing interval-parameter
      semi-infinite programming (ISIP) and fuzzy-chance-constrained programming (FCCP)
      by incorporating uncertainties expressed as dual uncertainties of functional
      intervals and multiple uncertainties of distributions with fuzzy-interval
      admissible probability of violating constraint within a general optimization
      framework. The binary-variable solutions represent the decisions of waste
      management-facility expansion, and the continuous ones are related to decisions
      of waste-flow allocation. The interval solutions can help decision-makers to
      obtain multiple decision alternatives, as well as provide bases for further
      analyses of tradeoffs between waste-management cost and system-failure risk. In
      the application to the City of Regina, Canada, two scenarios are considered. In
      Scenario 1, the City's waste-management practices would be based on the existing
      policy over the next 25 years. The total diversion rate for the residential waste
      would be approximately 14%. Scenario 2 is associated with a policy for waste
      minimization and diversion, where 35% diversion of residential waste should be
      achieved within 15 years, and 50% diversion over 25 years. In this scenario, not
      only landfill would be expanded, but also CF and MRF would be expanded. Through
      the scenario analyses, useful decision support for the City's solid-waste
      managers and decision-makers has been generated. Three special characteristics of
      the proposed method make it unique compared with other optimization techniques
      that deal with uncertainties. Firstly, it is useful for tackling multiple
      uncertainties expressed as intervals, functional intervals, probability
      distributions, fuzzy sets, and their combinations; secondly, it has capability in
      addressing the temporal variations of the functional intervals; thirdly, it can
      facilitate dynamic analysis for decisions of facility-expansion planning and
      waste-flow allocation within a multi-facility, multi-period and multi-option
      context.

PMID- 19854041
TI  - Optical probing of neuronal ensemble activity.
AB  - Neural computations are implemented in densely interconnected networks of
      excitable neurons as temporal sequences of coactive neuronal ensembles. Ensemble
      activity is produced by the interaction of external stimuli with internal states
      but has been difficult to directly study in the past. Currently, high-resolution
      optical imaging techniques are emerging as powerful tools to investigate neuronal
      ensembles in living animals and to characterize their spatiotemporal properties.
      Here we review recent advances of two-photon calcium imaging and highlight
      ongoing technical improvements as well as emerging applications. Significant
      progress has been made in the extent and speed of imaging and in the adaptation
      of imaging techniques to awake animals. These advances facilitate studies of the
      functional organization of local neural networks, their experience-dependent
      reconfiguration, and their functional impairment in diseases. Optical probing of
      neuronal ensemble dynamics in vivo thus promises to reveal fundamental principles
      of neural circuit function and dysfunction.

PMID- 19854042
TI  - Treatment of upper urinary tract urothelial carcinoma.
AB  - Upper urinary tract urothelial carcinoma (UUTUC) is relatively rare, occurring in
      only 5% of all urothelial cancers. It has not been as extensively studied and
      reviewed as carcinoma of the bladder. UUTUC has a propensity for multifocality,
      local recurrence, and development of metastases, which argues for an aggressive
      treatment approach. Open radical nephroureterectomy (ORNU) with removal of an
      ipsilateral bladder cuff still remains the gold standard treatment for patients
      with UUTUC and a normal contralateral kidney, which, however, is being challenged
      by minimally invasive approaches, such as endoscopic and laparoscopic approaches.
      They are rapidly evolving as reasonable alternatives of care depending on grade
      and stage of disease. Adjuvant therapy seems to be safe, although its efficacy is
      debatable. Immunotherapy appears to be most effective in patients with upper
      tract carcinoma in situ. Chemotherapy and radiotherapy also show some improvement
      in recurrence rates, but there have been no randomized, prospective trials. Gene
      and molecular-targeted therapy is expected. Several controversies remain in our
      management, including a selection of endoscopic versus laparoscopic approaches,
      management strategies on the distal ureter, the role of lymphadenectomy, and the
      value of immunotherapy, chemotherapy, radiotherapy and genetics and molecular
      markers in UUTUC. Aims of this paper are to critically review the treatment of
      UUTUC.

PMID- 19854043
TI  - Performance of pilot-scale vertical-flow constructed wetlands in responding to
      variation in influent C/N ratios of simulated urban sewage.
AB  - The performance response of planted and the unplanted wetlands to simulated
      wastewater with different ratios of carbon to nitrogen (C/N) was studied during a
      9-month period in greenhouse conditions. With different C/N ratios for influent
      water (C/N ratios 2.5:1, 5:1 and 10:1), average removal efficiencies for the
      unplanted and the planted wetlands were as follows: COD (41-52% and 59-68%), TN
      (24-48% and 25-62%), TP (35-64% and 59-71%) and TOC (22-37% and 16-33%). At C/N
      5:1, both systems performed most efficiently for removal of COD and TP. However,
      high N removal efficiency only occurred when C/N ratio ranged 2.5-5. Both
      wetlands exhibited good capabilities of total organic carbon removal at C/N 10:1.
      Maybe, appropriate control of the carbon or nitrogen source concentration and C/N
      ratio in the influent can achieve the optimal effect of nutrients removal.

PMID- 19854044
TI  - Characterization of biopolymeric flocculant (pectin) and organic synthetic
      flocculant (PAM): a comparative study on treatment and optimization in kaolin
      suspension.
AB  - Polyacrylamide (PAM), a commonly used organic synthetic flocculant, is known to
      have high reduction in turbidity treatment. However, PAM is not readily
      degradable. In this paper, pectin as a biopolymeric flocculant is used. The
      objectives are (i) to determine the characteristics of both flocculants (ii) to
      optimize the treatment processes of both flocculants in synthetic turbid waste
      water. The results obtained indicated that pectin has a lower average molecular
      weight at 1.63 x 10(5) and PAM at 6.00 x 10(7). However, the thermal degradation
      results showed that the onset temperature for pectin is at 165.58 degrees C,
      while the highest onset temperature obtained for PAM is at 235.39 degrees C. The
      optimum treatment conditions for the biopolymeric flocculant for flocculating
      activity was at pH 3, cation concentration at 0.55 mM, and pectin concentration
      at 3 mg/L. In contrast, PAM was at pH 4, cation concentration >0.05 mM and PAM
      concentration between 13 and 30 mg/L.

PMID- 19854045
TI  - Determination of ammonia and greenhouse gas emissions from land application of
      swine slurry: a comparison of three application methods.
AB  - In this study, the comparison and monitoring of the initial greenhouse gas (GHG)
      emissions using a flux chamber and gas analyzer from three different liquid
      manure application methods at a swine farm in Kentucky were carried out. Swine
      slurry was applied to farmland by row injection, surface spray, and Aerway
      injection. Ammonia and GHG concentrations were monitored immediately after
      application, 72 and 216h after application. The results showed that the initial
      ammonia flux ranged from 5.80 mg m(-2)h(-1) for the surface spray method to 1.80
      mg m(-2)h(-1) for the row injection method. The initial fluxes of methane ranged
      from 8.75 mg m(-2)h(-1) for surface spray to 2.27 mg m(-2)h(-1) for Aerway
      injection, carbon dioxide ranged from 4357 mg m(-2)h(-1) for surface spray to 60
      mg m(-2)h(-1) for row injection, and nitrous oxide ranged from 0.89 mg m(-2)h(-1)
      for surface spray to 0.22 mg m(-2)h(-1) for row injection. However, the Aerway
      injection method seemed to create the highest gas (GHG) concentrations inside the
      monitoring chambers at the initial application and produced the highest gas
      fluxes at subsequent sampling time (e.g., 72h after application). Nevertheless,
      the surface spray method appeared to produce the highest gas fluxes, and the row
      injection method appeared to emit the least amount of greenhouse gases into the
      atmosphere. Gas fluxes decreased over time and did not depend on the initial
      headspace concentration in the monitoring flux chambers.

PMID- 19854046
TI  - Stabilization of Candida rugosa lipase during transacetylation with vinyl
      acetate.
AB  - An optimally prepared Candida rugosa lipase aggregate cross-linked with bovine
      serum albumin, was found to overcome acetaldehyde deactivation during
      transacetylation of a series of benzyl alcohols with vinyl acetate. The
      formulation, under the same reaction conditions, exhibited 4-30x enhancement in
      the reaction rate as compared to the celite immobilized lyophilized formulation
      and 25-133x enhancement as compared to the free lyophilized enzyme depending upon
      the alcohol chosen. The racemic 1-phenylethanol, taken as one of the alcohols,
      underwent a more efficient enantioselective transacetylation giving 80%
      enantiomeric excess of the product, (R)-1-phenylethyl acetate, at 38% conversion
      (E = 15) within 24h while the enzyme immobilized on celite gave 83% enantiomeric
      excess at 18% conversion (E = 13) during the same period of time.

PMID- 19854047
TI  - Bamboo saccharification through cellulose solvent-based biomass pretreatment
      followed by enzymatic hydrolysis at ultra-low cellulase loadings.
AB  - The modified cellulose solvent- (concentrated phosphoric acid) and organic
      solvent- (95% ethanol) based lignocellulose fractionation (COSLIF) was applied to
      a naturally-dry moso bamboo sample. The biomass dissolution conditions were 50
      degrees C, 1 atm for 60 min. Glucan digestibility was 88.2% at an ultra-low
      cellulase loading of one filter paper unit per gram of glucan. The overall
      glucose and xylose yields were 86.0% and 82.6%, respectively. COSLIF efficiently
      destructed bamboo's fibril structure, resulting in a approximately 33-fold
      increase in cellulose accessibility to cellulase (CAC) from 0.27 to 9.14 m(2) per
      gram of biomass. Cost analysis indicated that a 15-fold decrease in use of costly
      cellulase would be of importance to decrease overall costs of biomass
      saccharification when cellulase costs are higher than $0.15 per gallon of
      cellulosic ethanol.

PMID- 19854048
TI  - Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput
      screening.
AB  - A novel series of isatin-based inhibitors of beta-secretase (BACE-1) have been
      identified using a virtual high-throughput screening approach. Structure-activity
      relationship studies revealed structural features important for inhibition.
      Docking studies suggest these inhibitors may bind within the BACE-1 active site
      through H-bonding interactions involving the catalytic aspartate residues.

PMID- 19854049
TI  - Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive
      antagonists of mGlu5.
AB  - A high-throughput cell-based screen identified a series of 6-substituted-4
      anilinoquinazolines as non-competitive antagonists of metabotropic glutamate
      receptor 5 (mGlu(5)). This Letter describes the SAR of this series and the
      profile of selected compounds in selectivity and radioligand binding assays.

PMID- 19854050
TI  - Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase
      inhibitor resistance in breast cancer cells.
AB  - A series of COX-2 selective inhibitor nimesulide derivatives were synthesized.
      Their anti-cell proliferation activities were evaluated with a long-term estrogen
      deprived MCF-7aro (LTEDaro) breast cancer cell line, which is the biological
      model of aromatase inhibitor resistance for hormone-dependent breast cancer.
      Compared to nimesulide which inhibited LTEDaro cell proliferation with an IC(50)
      at 170.30 microM, several new compounds showed IC(50) close to 1.0 microM.

PMID- 19854051
TI  - N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3
      phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor
      tyrosine kinase inhibitors.
AB  - A series of N-(4-(6,7-disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3
      phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases
      was designed and synthesized. The compounds were potent against these two enzymes
      with IC(50) values in the low nanomolar range in vitro, possessed favorable
      pharmacokinetic profiles and showed high efficacy in vivo in several human tumor
      xenograft models in mice.

PMID- 19854052
TI  - Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors.
      Part II.
AB  - A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte
      specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These
      type II inhibitors were optimized using a cellular Lck-dependent proliferation
      assay and are capable of inhibiting Lck at single-digit nanomolar concentrations.
      This scaffold is likely to serve a valuable template for developing potent
      inhibitors of a number of SFKs.

PMID- 19854053
TI  - Discovery and pharmacological characterization of aryl piperazine and piperidine
      ethers as dual acting norepinephrine reuptake inhibitors and 5-HT1A partial
      agonists.
AB  - Compounds that are both norepinephrine reuptake inhibitors (NRI) and 5-HT1(A)
      partial agonists may have the potential to treat neuropsychiatric disorders
      including attention deficit hyperactivity disorder (ADHD) and depression.
      Targeted screening of NRI-active compounds for binding to the 5-HT(1A) receptor
      provided a series of thiomorpholinone hits with this dual activity profile.
      Several iterations of design, synthesis, and testing led to substituted
      piperidine diphenyl ethers which are potent NRIs with 5-HT1(A) partial agonist
      properties. In addition, optimization of these molecules provided compounds which
      exhibit selectivity for NRI over the dopamine (DAT) and serotonin (SERT) reuptake
      transporters. Monoamine and 5-HT(1A) in vitro functional activities for select
      compounds from the developed piperidine diphenyl ether series are also presented.

PMID- 19854054
TI  - Nitric oxide-donating carbonic anhydrase inhibitors for the treatment of open
      angle glaucoma.
AB  - Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to
      a dorzolamide scaffold were investigated. Several compounds were synthesized and
      their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in
      vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed
      different degrees of potency and selectivity to hCA II. A high resolution X-ray
      crystal structure for the CA II adduct with 8 confirmed the high affinity of this
      class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and
      efficacious NO-mediated properties as assessed by their vascular relaxant effect
      on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6
      exerted potent intraocular pressure (IOP) lowering effects in vivo in
      normotensive rabbits thereby anticipating their potential for the treatment of
      hypertensive glaucoma.

PMID- 19854055
TI  - Immunolabelling and flow cytometry as new tools to explore dysferlinopathies.
AB  - Dysferlinopathies are autosomal recessive muscular dystrophies caused by DYSF
      mutations, which lead to a reduced amount or a complete lack of dysferlin. One
      step in dysferlinopathies diagnosis consists in Western blot analysis of proteins
      extracted from muscle biopsy, or blood monocytes. We have taken advantage of
      dysferlin expression in monocytes to develop a whole blood flow cytometry (WBFC),
      using antibodies directed against dysferlin. Six patients were submitted to WBFC
      analysis and immunofluorescence analysis on monocytes. Results obtained are
      correlated to Western blot from monocytes and muscle biopsies. The possible
      usefulness of this flow cytometry analysis in routine diagnosis is presented.

PMID- 19854057
TI  - Effects of obstacle height on obstacle crossing in mild Parkinson's disease.
AB  - The aim of this study was to compare the locomotor behavior of people with
      Parkinson's disease (PD) and healthy older adults during obstacle negotiation,
      both in the approaching and crossing phases. Twelve people with idiopathic PD,
      with mild to moderate disease, and 12 healthy individuals (CG) walked across an
      8m pathway for three obstacle conditions: no obstacle, low obstacle and high
      obstacle. Each performed five trials for each obstacle condition. Performance was
      more disturbed for the high obstacle than the low obstacle. During the approach
      phase, people with PD demonstrated shorter stride length (F(1,22)=8.55, P=0.008)
      and greater stride duration (F(1,22)=7.371, P=0.013) than controls. Those with PD
      also increased their stance phase durations (F(1,22)=7.426, P=0.012) for both
      obstacle conditions, while the CG maintained comparable step durations for all
      conditions. For the crossing phase, people with PD demonstrated shorter step
      length (F(1,22)=9.699, P=0.005) over the obstacle. Leading limbs were closer to
      the obstacle, before and after crossing. Thus PD hypokinesia compromises the
      approach and crossing phases of obstacle negotiation.

PMID- 19854056
TI  - Dynamic chromosome movements during meiosis: a way to eliminate unwanted
      connections?
AB  - Dramatic chromosome motion is a characteristic of mid-prophase of meiosis that is
      observed across broadly divergent eukaryotic phyla. Although the specific
      mechanisms underlying chromosome motions vary among organisms studied to date,
      the outcome is similar in all cases: vigorous back-and-forth movement (as fast as
      approximately 1mum/sec for budding yeast), led by chromosome ends (or near-end
      regions), and directed by cytoskeletal components via direct association through
      the nuclear envelope. The exact role(s) of these movements remains unknown,
      although an idea gaining currency is that movement serves as a stringency factor,
      eliminating unwanted inter-chromosomal associations or entanglements that have
      arisen as part of the homolog pairing process and, potentially, unwanted
      associations of chromatin with the nuclear envelope. Turbulent chromosome
      movements observed during bipolar orientation of chromosomes for segregation
      could also serve similar roles during mitosis. Recent advances shed light on the
      contribution of protein complexes involved in the meiotic movements in chromosome
      dynamics during the mitotic program.

PMID- 19854058
TI  - Age and electromyographic frequency alterations during walking in children with
      cerebral palsy.
AB  - The use of surface electromyography (sEMG) recorded during ambulation has
      provided valuable insight into motor development and changes with age in the
      pediatric population. However, no studies have reported sEMG differences with age
      in the children with cerebral palsy (CP). In this study, data from 50 children
      were divided retrospectively into four groups, representing either an older
      (above the age of seven years) or younger (below the age of seven years) age
      group with either typical development (TD) or CP. Data were analyzed from 16
      children in the younger age group with TD, and eight in the older age group with
      TD. Data were also available from 14 in the younger age group with CP, and 12 in
      the older age group with CP. SEMG signals from the rectus femoris (RF) and medial
      hamstring (MH) were analyzed using wavelet techniques to examine time-frequency
      content. RF muscle activity was statistically different between all groups
      (p<0.001), with an elevated instantaneous mean frequency (IMNF) in the older TD
      group than the younger TD group, an elevated IMNF in the younger CP group than
      the older CP group, and elevated IMNF in both CP groups compared to both TD
      groups. Activity for the MH muscle followed the same pattern except for the CP
      young and old group comparison, which indicated no difference. The results
      indicate that differences in neuromuscular activation exist between younger and
      older groups of children with both TD and CP, and may provide new insight into
      muscle activity pattern changes during the development of walking.

PMID- 19854059
TI  - Prescribers' attitudes toward elderly breast cancer patients. Discrimination or
      empathy?
AB  - Advancing age is often associated with co-morbidities. Patients' chronological
      and physiological ages do not always correspond. Elderly patients are often
      excluded from clinical trials and given sub-optimum treatment. In this context,
      the question of equity in access to health care arises. A specially designed
      questionnaire was mailed to French oncologists to determine what factors
      influenced them and to elicit their medical practice using four clinical cases.
      Significant differences in treatment choice depending only on patient's age were
      observed. The likelihood of an elderly breast cancer patient undergoing
      chemotherapy was found to depend on physician specialty and gender, kind of care
      structure, physician's perception of the age at which patients become elderly,
      and their knowledge about geriatric assessments. Some physicians did not always
      prescribe potentially beneficial treatments when dealing with elderly patients.
      Given the multidimensional nature of the care process, patients' preferences
      should be taken into account in medical decision-making.

PMID- 19854062
TI  - Does skeletal muscle oxidative stress initiate insulin resistance in genetically
      predisposed individuals?
AB  - Reactive oxygen species (ROS) are postulated to be a common trigger of insulin
      resistance. For example, treatment of adipocytes with either tumor-necrosis
      factor-alpha or dexamethasone increases ROS before impairing glucose uptake.
      Similarly, treatment with mitochondria-specific antioxidants preserves insulin
      sensitivity in animal models of insulin resistance. However, it remains unclear
      whether ROS contribute to insulin resistance in humans. First-degree relatives
      (FDRs) of type 2 diabetes subjects are at increased risk of developing insulin
      resistance and type 2 diabetes. Here we review the documented metabolic
      impairments in FDRs that could contribute to insulin resistance via increased
      oxidative stress. We propose that lipotoxic intermediates and lipid peroxides in
      skeletal muscle interfere with insulin signaling and might cause insulin
      resistance in these 'at risk' individuals.

PMID- 19854061
TI  - Hepatitis C virus hijacks host lipid metabolism.
AB  - Hepatitis C virus (HCV) enhances its replication by modulating host cell lipid
      metabolism. HCV circulates in the blood in association with lipoproteins. HCV
      infection is associated with enhanced lipogenesis, reduced secretion, and beta
      oxidation of lipids. HCV-induced imbalance in lipid homeostasis leads to
      steatosis. Many lipids are crucial for the virus life cycle, and inhibitors of
      cholesterol/fatty acid biosynthetic pathways inhibit virus replication,
      maturation and secretion. HCV negatively modulates the synthesis and secretion of
      very low-density lipoproteins (VLDL). Components involved in VLDL assembly are
      also required for HCV morphogenesis/secretion, suggesting that HCV co-opts the
      VLDL secretory pathway for its own secretion. This review highlights HCV-altered
      lipid metabolic events that aid the virus life cycle and ultimately promote liver
      disease.

PMID- 19854060
TI  - The molecular basis of hypopituitarism.
AB  - Hypopituitarism is defined as the deficiency of one or more of the hormones
      secreted by the pituitary gland. Several developmental factors necessary for
      pituitary embryogenesis and hormone secretion have been described, and mutations
      of these genes in humans provide a molecular understanding of hypopituitarism.
      Genetic studies of affected patients and their families provide insights into
      possible mechanisms of abnormal pituitary development; however, mutations are
      rare. This review characterizes several of these developmental proteins and their
      role in the pathogenesis of hypopituitarism. Continuing research is required to
      better understand the complexities and interplay between these pituitary factors
      and to make improvements in genetic diagnosis that can lead to early detection
      and provide a future cure.

PMID- 19854064
TI  - Uncovering patterns of forearm muscle activity using multi-channel
      mechanomyography.
AB  - A coordinated activation of distal forearm muscles allows the hand and fingers to
      be shaped during movement and grasp. However, little is known about how the
      muscle activation patterns are reflected in multi-channel mechanomyogram (MMG)
      signals. The purpose of this study is to determine if multi-site MMG signals
      exhibit distinctive patterns of forearm muscle activity. MMG signals were
      recorded from forearm muscle sites of nine able-bodied participants during hand
      movement. By using 14 features selected by a genetic algorithm and classified by
      a linear discriminant analysis classifier (LDA), we show that MMG patterns are
      specific and consistent enough to identify 7+/-1 hand movements with an accuracy
      of 90+/-4%. MMG-based movement recognition required a minimum of three recording
      sites. Further, by classifying five classes of contraction patterns with 98+/-3%
      accuracy from MMG signals recorded from the residual limb of an amputee
      participant, we demonstrate that MMG shows pattern-specificity even in the
      absence of typical musculature. Multi-site monitoring of the RMS of MMG signals
      is suggested as a method of estimating the relative contributions of muscles to
      motor tasks. The patterns in MMG facilitate our understanding of the mechanical
      activity of muscles during movement.

PMID- 19854063
TI  - Ion trap collision-induced dissociation of locked nucleic acids.
AB  - Gas-phase dissociation of model locked nucleic acid (LNA) oligonucleotides and
      functional LNA-DNA chimeras have been investigated as a function of precursor ion
      charge state using ion trap collision-induced dissociation (CID). For the model
      LNA 5 and 8 mer, containing all four LNA monomers in the sequence, cleavage of
      all backbone bonds, generating a/w-, b/x-, c/y-, and d/z-ions, was observed with
      no significant preference at lower charge states. Base loss ions, except loss of
      thymine, from the cleavage of N-glycosidic bonds were also present. In general,
      complete sequence coverage was achieved in all charge states. For the two LNA-DNA
      chimeras, however, dramatic differences in the relative contributions of the
      competing dissociation channels were observed among different precursor ion
      charge states. At lower charge states, sequence information limited to the a
      Base/w-fragment ions from cleavage of the 3'C-O bond of DNA nucleotides, except
      thymidine (dT), was acquired from CID of both the LNA gapmer and mixmer ions. On
      the other hand, extensive fragmentation from various dissociation channels was
      observed from post-ion/ion ion trap CID of the higher charge state ions of both
      LNA-DNA chimeras. This report demonstrates that tandem mass spectrometry is
      effective in the sequence characterization of LNA oligonucleotides and LNA-DNA
      chimeric therapeutics.

PMID- 19854065
TI  - Passive knee movement-induced modulation of the soleus H-reflex and alteration in
      the fascicle length of the medial gastrocnemius muscle in humans.
AB  - In humans, an inhibitory via Ia afferent pathway from the medial gastrocnemius
      (MG) to the soleus (SOL) motoneuron pool has been suggested. Herein, we examined
      the relation between MG fascicle length changes and the SOL H-reflex modulation
      during passive knee movement. Twelve subjects performed static and passive (5
      degrees s(-1)) knee movement tasks with the ankle immobilized using an isokinetic
      dynamometer in sitting posture. The maximal H- and M-waves were measured at four
      target angles (20 degrees, 40 degrees, 60 degrees, and 80 degrees flexion from
      full knee extension). The MG fascicles length and velocity were measured using a
      B-mode ultrasonic apparatus. Results demonstrated that the SOL Hmax/Mmax; i.e.,
      ratio of the maximal H- to M-waves, was attenuated with increasing MG fascicle
      length in static tasks. The SOL Hmax/Mmax at 20 degrees was significantly
      attenuated compared with 60 degrees and 80 degrees with increasing MG fascicle
      length and lengthening velocity in passive knee extension. However, no
      significant differences in the SOL Hmax/Mmax were found across the target angles
      in the passive knee flexion task. In conclusion, as muscle spindles increase
      their discharge with lengthening fascicle velocity, but keep silent when
      fascicles shorten, our data suggest that lengthening the MG facilitates an
      inhibitory Ia pathway from MG to SOL, and modulates SOL motoneuron activity
      during movements.

PMID- 19854066
TI  - Endovascular recanalization of symptomatic portomesenteric venous obstruction
      after pancreaticoduodenectomy and radiation.
AB  - Intraoperative radiation therapy (RT) may improve outcomes after
      pancreaticoduodenectomy for periampullary cancer; however, there is a 20% risk of
      late portomesenteric venous obstruction. This retrospective study evaluated the
      percutaneous treatment of portomesenteric venous obstruction that occurred a mean
      of 10 months after pancreaticoduodenectomy and intraoperative RT. Five patients
      with medically refractory ascites and portomesenteric obstruction on computed
      tomographic angiography had successful recanalization with elimination of the
      pressure gradient and no procedural complications. One patient showed no
      improvement clinically. Recurrent ascites after stent occlusion was successfully
      treated in two patients. Percutaneous transhepatic recanalization appears to be a
      safe and effective therapy in this population.

PMID- 19854067
TI  - Treatment of refractory iatrogenic femoral artery pseudoaneurysm with a vascular
      closure device.

PMID- 19854068
TI  - Optimization of radioembolic effect with extended-shelf-life yttrium-90
      microspheres: results from a pilot study.
AB  - PURPOSE: To evaluate the safety and efficacy of yttrium-90 ((90)Y)
      radioembolization with extended-shelf-life glass microspheres. We postulated that
      this approach, for the same planned tissue dose of 120 Gy, would increase the
      embolic load, improve distribution, and result in enhanced tumor response without
      causing additional adverse events. MATERIALS AND METHODS: Between June 2007 and
      September 2008, 50 patients with extensive tumor burden and/or markedly
      hypervascular tumors (13 hepatocellular carcinomas, and 37 liver metastases)
      underwent radioembolization with extended-shelf-life microspheres at a planned
      dose of 120 Gy. Baseline and follow-up imaging and laboratory data were obtained.
      Response in the target lesion was assessed with cross-sectional imaging by using
      World Health Organization (WHO) and European Association for the Study of the
      Liver (EASL) guidelines. RESULTS: The mean delivered radiation dose was 126 Gy.
      The mean increase in embolic load with this approach was 111%, corresponding to
      an increase from 3.6 to 7.3 million microspheres. Clinical toxicities included
      fatigue (28 patients, 56%), abdominal pain (19 patients, 38%), and
      nausea/vomiting (six patients, 12%). Grade 3-4 bilirubin toxicity was seen in one
      patient. Two gastroduodenal ulcers were observed. With cross-sectional imaging,
      response rates according to WHO and EASL guidelines were 51% and 69%,
      respectively. CONCLUSIONS: The results demonstrate the safety and efficacy of
      extended-shelf-life (90)Y glass microspheres. The increased embolic load and
      lowered activity per microsphere theoretically resulted in better tumor coverage
      and, hence, improved response rates. This standardizable treatment paradigm
      provides a minimally embolic therapy for liver tumors.

PMID- 19854070
TI  - Painful osteolytic metastasis involving the anterior and posterior arches of C1:
      percutaneous vertebroplasty with local anesthesia.

PMID- 19854069
TI  - Delivery site of perivascular endothelial cell matrices determines control of
      stenosis in a porcine femoral stent model.
AB  - PURPOSE: Endothelial cells, grown within gelatin matrices and implanted onto the
      adventitia of injured vessels, inhibit stenosis in experimental models. To
      determine if this technology could be adapted for minimally invasive procedures,
      the authors compared the effects of cells in an implantable sponge to that of an
      injectable formulation and investigated the importance of delivery site in a
      stent model. MATERIALS AND METHODS: Stents were implanted in the femoral arteries
      of 30 pigs. This was followed by perivascular implantation of sponges or
      injection of particles containing allogeneic endothelial cells. Controls received
      acellular matrices or nothing. The effects of delivery site were assessed by
      injecting cellular matrices into or adjacent to the perivascular tissue or into
      the neighboring muscle. Animals were sacrificed after 28 days. Pre-sacrifice
      angiograms and tissue sections were evaluated for stenosis. RESULTS: Arteries
      treated with cellular matrices had a 55%-63% decrease in angiographic stenosis (P
      < .05) and a 38%-43% reduction in histologic stenoses (P < .05) compared to
      controls. Intimal area was greatest when cellular matrices were delivered into
      the muscle (6.35 mm(2) +/- 0.95) rather than into or adjacent to the perivascular
      tissue (4.05 mm(2) +/- 0.56 and 4.73 mm(2) +/- 0.53, respectively; P < .05).
      CONCLUSIONS: Perivascular endothelial cell matrices reduced stenosis after stent
      induced injury. The effects were not dependent on the formulation but appeared to
      be dependent on delivery site. Minimally invasive injections of endothelial cell
      matrices to the adventitia of arteries following peripheral interventions may
      decrease restenosis rates.

PMID- 19854071
TI  - Sclerotherapy for peribiliary cysts accompanied by biliary stenosis.

PMID- 19854072
TI  - Fluoroscopically guided percutaneous jejunostomy with use of a 21-gauge needle: a
      prospective study in 51 patients.
AB  - PURPOSE: To assess the safety and clinical efficacy of fluoroscopically guided
      percutaneous jejunostomy with use of a 21-gauge needle and a single anchor
      technique in 51 patients. MATERIALS AND METHODS: From November 2006 to January
      2009, 51 consecutive patients (42 men and nine women; mean age, 63.7 years)
      underwent percutaneous jejunostomy under fluoroscopic guidance. A 7.5-F
      multifunctional coil catheter was used to insufflate the jejunum. The distended
      jejunum was punctured with a 21-gauge needle, with the inserted coil catheter as
      the target. A single anchor was used. The technical success, number of punctures,
      procedure time, complications, and follow-up data including 30-day mortality rate
      were evaluated. RESULTS: The technical success rate was 100%, and the single
      anchor technique was used in all but one patient, in whom three anchors were
      used. The mean number of punctures was 1.7 (range, 1-4), and the mean procedure
      time was 14.8 minutes (range, 7-29 min). Peritonitis was a major complication in
      two patients (3.9%), who were treated by changing the catheters from 14 F to 16 F
      and performing percutaneous drainage procedures. Three minor complications were
      encountered: superficial cellulitis (n = 2) and severe puncture site pain (n =
      1). The 30-day mortality rate was 5.9% (three of 51), although none of the deaths
      could be attributed to the jejunostomy procedures. CONCLUSIONS: Fluoroscopically
      guided percutaneous jejunostomy with use of a 21-gauge needle and the single
      anchor technique seems to be safe and effective, with high technical success and
      low complication rates.

PMID- 19854073
TI  - The novel 2009 H1N1 influenza virus pandemic: unique considerations for programs
      in cardiothoracic transplantation.
AB  - The emergence of the novel 2009 H1N1 influenza virus highlights unique aspects of
      transplant care that will require heightened vigilance in coming months.
      Recognition of the syndrome, aggressive diagnosis and early treatment should be
      paired with active preventative measures to stem the impact of infection in the
      transplant population. This special advisory addresses issues relevant to
      cardiothoracic transplant candidates, selection of donors, recipient management
      and those patients with mechanical circulatory support devices.

PMID- 19854075
TI  - Effectiveness of insoles used for the prevention of ulceration in the neuropathic
      diabetic foot: a systematic review.
AB  - CONTEXT: Ulceration can be a debilitating and costly complication of the
      neuropathic diabetic foot. Insoles inserted into footwear are routinely used in
      clinical practice to help to prevent ulceration. AIM AND SCOPE OF THE REVIEW:
      This review evaluated the effectiveness of insoles used for the prevention of
      ulcer in the neuropathic diabetic foot. METHODS: Databases were searched from
      inception to 2008, supplemented by hand searching of references and grey
      literature. Data extraction and methodological quality assessment were
      independently conducted by two reviewers following the recommendations of the
      Centre for Reviews and Dissemination. RESULTS: A total of five trials met the
      inclusion criteria: two randomised control trials (RCTs), two case control
      studies, and one follow-up study. The methodological quality of the majority of
      studies was poor. Omitted details regarding the generalisability of results made
      study comparison and inference to practice difficult. There is a small amount of
      limited evidence indicating that insoles are effective in reducing incidence of
      ulceration and reducing plantar peak pressures in the diabetic neuropathic foot.
      No study included economic analysis or patient-based outcome measures.
      CONCLUSIONS: Insoles appear of use for the prevention of neuropathic diabetic
      foot ulceration, although evidence is limited. Clinical recommendation regarding
      type and specification of insole is not possible at this time. There is an
      essential need for a large well-designed RCT comparing different types of
      commonly used insole for the prevention of ulceration in the diabetic neuropathic
      foot. Outcome measures should include patient perceptions of the effectiveness
      and cost-effectiveness analysis.

PMID- 19854074
TI  - Sitagliptin treatment of patients with type 2 diabetes does not affect CD4+ T
      cell activation.
AB  - Dipeptidyl peptidase IV (DPP4) inhibitors have recently become widely used for
      treating type 2 diabetes, but in meta-analyses are associated with a mildly
      increased risk of all-cause infections. CD26 is a cell-surface form of DPP4 which
      can costimulate T-cell proliferation, raising the possibility that DPP4
      inhibitors might adversely affect immune function. To address this issue in an
      observational study, two groups of 20 subjects each were recruited from a private
      endocrinology practice; one group consisted of type 2 diabetes patients treated
      for at least 6 months with the DPP4 inhibitor, sitagliptin, whereas patients in
      the other group had never been treated with this agent. The groups were similar
      with regard to sex and racial composition, body mass index, hemoglobin A(1c), and
      use of other medications for diabetes, but the sitagliptin group was slightly
      older. A blood sample from each patient was analyzed for CD4+ T-cell activation
      in response to phytohemagglutinin using adenosine triphosphate (ATP)-stimulated
      bioluminescence. There was not a significant difference in T-cell activation
      between the treatment groups (median, 419 and 481 ng/ml ATP in the groups that
      were and were not treated with sitagliptin, respectively). Thus the observed
      increased rate of infection in diabetic patients treated with sitagliptin cannot
      be explained by a major effect on T-cell activation. Randomized studies,
      preferably using several assays of immune function, should be performed to
      confirm and extend these findings.

PMID- 19854076
TI  - The effect of L-arginine and L-NAME on pentylenetetrazole induced seizures in
      ovariectomized rats, an in vivo study.
AB  - The role of ovarian hormones and nitric oxide (NO) on seizure and their
      interaction have been widely investigated. The present study carried out to
      evaluate the effect of chronic administration of L-arginine (LA) and L-NAME (LN)
      on pentylenetetrazole (PTZ) induced epilepsy in ovariectomized (OVX) and naive
      female rats. Fourty-eight female rats were randomly divided into six groups (n=8)
      as follows: (1) sham, (2) ovarectomized (OVX), (3) sham-LA, (4) sham-LN, (5) OVX
      LA, and (6) OVX-LN. The animals of sham-LA and OVX-LA received daily injection of
      500 mg/kg L-arginine (i.p.) during 4 weeks. Sham-LN and OVX-LN were treated by 10
      mg/kg L-NAME (i.p.) daily for 4 weeks. The animals of sham and OVX groups
      received 1 ml/kg saline (i.p.) instead of L-arginine and L-NAME. The latencies to
      minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) after
      intraperitoneal injection of penetylenetetrazole (PTZ, 90 mg/kg) was recorded and
      compared between groups. A significant increase in the GTCS, but not MCS, latency
      was seen in OVX rats in comparison with sham-operated animals. Pretreatment of
      animals with L-NAME resulted in a significant increase in the GTCS and MCS
      latencies in sham group while no significant effects were seen in OVX rats. On
      the contrary, while pretreatment with L-arginine had no effects on MCS and GTCS
      latencies in sham group, a significant decrease in GTCS latency was observed in
      OVX rats. It is concluded that ovarian sex hormones affect seizure thresholds
      induced by PTZ and NO has a role on seizures susceptibility following PTZ
      administration. This NO effect might be differing in the presence or absence of
      ovarian hormones, but further investigations need to be done.

PMID- 19854077
TI  - CIS is a surrogate marker of genetic instability and field carcinogenesis in the
      urothelial mucosa.
AB  - OBJECTIVE: To investigate whether carcinoma in situ (CIS) lesion could be
      considered a surrogate marker of urothelium genetic instability and field
      carcinogenesis or not, we evaluated DNA content, p53 overexpression, and
      proliferative index (Ki-67 expression) in primary tumor, in tumor-adjacent
      mucosa, and distant urothelial mucosa with and without presence of CIS. PATIENTS
      AND METHODS: A retrospective study in radical cystectomy specimens from 49
      patients was carried out. All the lesions present in each cystectomy specimen
      were studied, including the tumor area and the adjacent mucosa (AM). Whenever
      possible, the distant mucosa (DM) was also studied. When CIS was detected, this
      lesion and the surrounding normal mucosa were also studied. The 49 tumor areas
      included high grade papillary urothelial carcinoma (HGP) in 19 cases (38.8%) and
      invasive urothelial cell carcinomas in 30 cases (61.2%). The nuclear DNA content
      of cancer cells was evaluated using image cytometry allowing the determination of
      the DNA ploidy and 5cER parameters. The p53 and Ki-67 immunoexpression was
      evaluated by immunohistochemistry. RESULTS: CIS lesions were observed in the AM
      and DM of both tumor groups: 15.8% and 15.4% in AM and DM, for each one of them,
      in HGP group and 26.7% and 22.2% in AM and DM, for each one of them, in invasive
      tumors group. In CIS lesion aneuploid DNA content, p53 overexpression and high
      proliferative labeling index were observed. The so-called normal mucosa (AM and
      DM) with and without focus of CIS lesions were compared for genetic instability
      and molecular alterations profile. Statistical differences were observed between
      the normal mucosa with and without CIS: the so-called normal mucosa areas with
      focus of CIS revealed significantly higher frequencies of DNA content
      alterations, p53 overexpression, and higher proliferative index. These
      differences were significantly different in the invasive UCC group, but this
      profile it is also present in HPG group. CONCLUSION: This study points out that
      CIS is a marker of genetic instability of the urothelium mucosa. The CIS
      surrounding morphologically normal urothelium showed a high frequency of abnormal
      DNA content, with high percentage of clear aneuploid cells (high 5cER), p53
      mutated protein expression, and a proliferative status underlying a field
      carcinogenesis. These alterations in normal mucosa were not found when CIS was
      not present.

PMID- 19854078
TI  - Treatment of brain metastases from renal cell cancer.
AB  - OBJECTIVE: To evaluate disease pattern, patient characteristics, and survival in
      patients treated for brain metastases from renal cell carcinoma. METHODS:
      Retrospective analysis of all patients with brain metastases from renal cell
      carcinoma treated between 1983 and 2009 in northern Norway. RESULTS: The time
      interval between first cancer diagnosis and brain metastases was dependent on
      initial TNM stage (median 42 months in stage II vs. 10 months in both stage III
      and stage IV). Only few patients did not harbor extracranial metastases. Systemic
      therapy after diagnosis of brain metastases has been used in only three patients.
      Surgical resection and/or radiosurgery have been administered in 34% of patients,
      but whole-brain radiotherapy (WBRT) alone remained the cornerstone. Median
      survival was 4.1 months (3.7 months in the WBRT alone group, 10.1 months in the
      surgery and/or radiosurgery group). Two factors were significantly associated
      with better survival: solitary brain metastasis and age <=64 years. The
      prognostic impact of the recursive partitioning analysis classes was not
      confirmed, while the new graded prognostic assessment index performed better.
      CONCLUSIONS: Surgical resection and/or radiosurgery contribute to prolonged
      survival. As most patients harbor extracranial metastases that threaten their
      lives, systemic treatment theoretically might play a role in the management of
      these patients, but more data need to be collected to confirm the clinical impact
      of immunotherapy, angiogenesis inhibition, and other signal transduction
      inhibitor approaches.

PMID- 19854079
TI  - Intraluminal fibre-tip centring can improve endovenous laser ablation: a
      histological study.
AB  - OBJECTIVE: In this histological study, the lateral saphenous vein of the goat was
      treated using a laser fibre to which a tulip-shaped, self-expandable catheter had
      been fixed to achieve endovenous laser ablation (EVLA). The catheter centres the
      laser fibre in the vein preventing direct contact with the vein wall. This study
      aims to establish whether prevention of direct contact between the fibre tip and
      the vein wall prevents ulceration and perforation of the vein wall and perivenous
      tissue destruction. MATERIALS AND METHODS: Ten lateral saphenous veins were
      treated, using the tulip catheter, in goats under general anaesthesia. Ten more
      veins were treated with a normal bare fibre. We used a 980 nm diode laser to
      provide the energy. Postoperatively the veins were removed immediately, at 10
      days and after 3 weeks for histological examination. Destruction of the vessel
      wall was measured and perivenous tissue destruction was quantified using a graded
      scale. RESULTS: Ulceration and perforation were prevented when using the tulip
      catheter. It also achieved more even vein wall necrosis. Tulip-catheter-treated
      veins show a transmural vein wall necrosis in, on average, 80% of the total
      circumference compared to 64% in bare-fibre treated veins. Less perivenous tissue
      destruction was seen with the new catheter (perivenous tissue destruction scale:
      tulip catheter: 1.7 vs. bare fibre: 3.8). Three weeks after treatment, we found
      regression of the perivenous tissue destruction as the healing process continued.
      CONCLUSIONS: EVLA using the tulip catheter avoids ulceration and perforation of
      the vein associated with treatment using a bare fibre. It also results in more
      even circumferential vein wall necrosis and less perivenous tissue destruction.

PMID- 19854080
TI  - Pharmacokinetics of oral gabapentin in greyhound dogs.
AB  - The purpose of this study was to assess the pharmacokinetics of gabapentin in
      healthy greyhound dogs after single oral doses targeted at 10 and 20mg/kg PO. Six
      healthy greyhounds were enrolled (3 males, 3 females). Blood was obtained at
      predetermined times for the measurement of gabapentin plasma concentrations by
      liquid chromatography/mass spectrometry. Pharmacokinetic parameters were
      determined with computer software. The actual mean (and range) doses administered
      were 10.2 (9.1-12.0) mg/kg and 20.5 (18.2-24) mg/kg for the 10mg/kg and 20mg/kg
      targeted dose groups. The mean C(MAX) for the 10 and 20mg/kg groups were 8.54 and
      13.22 microg/mL at 1.3 and 1.5h, and the terminal half-lives were 3.3 and 3.4h,
      respectively. The relative bioavailability of the 10mg/kg group was 1.13 compared
      to the 20mg/kg group. Gabapentin was rapidly absorbed and eliminated in dogs,
      indicating that frequent dosing is needed to maintain minimum targeted plasma
      concentrations.

PMID- 19854082
TI  - DNP enhanced frequency-selective TEDOR experiments in bacteriorhodopsin.
AB  - We describe a new approach to multiple (13)C-(15)N distance measurements in
      uniformly labeled solids, frequency-selective (FS) TEDOR. The method shares
      features with FS-REDOR and ZF- and BASE-TEDOR, which also provide quantitative
      (15)N-(13)C spectral assignments and distance measurements in U-[(13)C,(15)N]
      samples. To demonstrate the validity of the FS-TEDOR sequence, we measured
      distances in [U-(13)C,(15)N]-asparagine which are in good agreement with other
      methods. In addition, we integrate high frequency dynamic nuclear polarization
      (DNP) into the experimental protocol and use FS-TEDOR to record a resolved
      correlation spectrum of the Arg-(13)C(gamma)-(15)N(epsilon) region in [U
      (13)C,(15)N]-bacteriorhodopsin. We resolve six of the seven cross-peaks expected
      based on the primary sequence of this membrane protein.

PMID- 19854083
TI  - Variable helix elongation as a tool to modulate RNA alignment and motional
      couplings.
AB  - The application of residual dipolar couplings (RDCs) in studies of RNA structure
      and dynamics can be complicated by the presence of couplings between collective
      helix motions and overall alignment and by the inability to modulate overall
      alignment of the molecule by changing the ordering medium. Here, we show for a 27
      nt TAR RNA construct that variable levels of helix elongation can be used to
      alter both overall alignment and couplings to collective helix motions in a semi
      predictable manner. In the absence of elongation, a four base-pair helix II
      capped by a UUCG apical loop exhibits a higher degree of order compared to a six
      base-pair helix I (theta(I)/theta(II)=0.56+/-0.1). The principal S(zz) direction
      is nearly parallel to the axis of helix II but deviates by approximately 40
      degrees relative to the axis of helix I. Elongating helix I by three base-pairs
      equalizes the alignment of the two helices and pushes the RNA into the motional
      coupling limit such that the two helices have comparable degrees of order
      (theta(I)/theta(II)=0.92+/-0.04) and orientations relative to S(zz) (
      approximately 17 degrees ). Increasing the length of elongation further to 22
      base-pairs pushes the RNA into the motional decoupling limit in which helix I
      dominates alignment (theta(II)/theta(I)=0.45+/-0.05), with S(zz) orientated
      nearly parallel to its helix axis. Many of these trends can be rationalized using
      PALES simulations that employ a previously proposed three-state dynamic ensemble
      of TAR. Our results provide new insights into motional couplings, offer
      guidelines for assessing their extent, and suggest that variable degrees of helix
      elongation can allow access to independent sets of RDCs for characterizing RNA
      structural dynamics.

PMID- 19854085
TI  - A tensor model and measures of microscopic anisotropy for double-wave-vector
      diffusion-weighting experiments with long mixing times.
AB  - Experiments with two diffusion-weighting periods applied successively in a single
      experiment, so-called double-wave-vector (DWV) diffusion-weighting experiments,
      are a promising tool for the investigation of material or tissue structure on a
      microscopic level, e.g. to determine cell or compartment sizes or to detect pore
      or cell anisotropy. However, the theoretical descriptions presented so far for
      experiments that aim to investigate the microscopic anisotropy with a long mixing
      time between the two diffusion weightings, are limited to certain wave vector
      orientations, specific pore shapes, and macroscopically isotropic samples. Here,
      the signal equations for fully restricted diffusion are re-investigated in more
      detail. A general description of the signal behavior for arbitrary wave vector
      directions, pore or cell shapes, and orientation distributions of the pores or
      cells is obtained that involves a fourth-order tensor approach. From these
      equations, a rotationally invariant measure of the microscopic anisotropy, termed
      MA, is derived that yields information complementary to that of the (macroscopic)
      anisotropy measures of standard diffusion-tensor acquisitions. Furthermore, the
      detailed angular modulation for arbitrary cell shapes with an isotropic
      orientation distribution is derived. Numerical simulations of the MR signal with
      a Monte-Carlo algorithms confirm the theoretical considerations. The extended
      theoretical description and the introduction of a reliable measure of the
      microscopic anisotropy may help to improve the applicability and reliability of
      corresponding experiments.

PMID- 19854084
TI  - Selective detection of single-enantiomer spectrum of chiral molecules aligned in
      the polypeptide liquid crystalline solvent: transition selective one-dimensional
      1H-1H COSY.
AB  - One-dimensional (1D) proton NMR spectra of enantiomers are generally
      undecipherable in chiral orienting poly-gamma-benzyl-L-glutamate (PBLG)/CDCl(3)
      solvent. This arises due to large number of couplings, in addition to
      superposition of spectra from both the enantiomers, severely hindering the (1)H
      detection. On the other hand in the present study the benefit is derived from the
      presence of several couplings among the entire network of interacting protons.
      Transition selective 1D (1)H-(1)H correlation experiment (1D-COSY) which utilizes
      the coupling assisted transfer of magnetization not only for unraveling the
      overlap but also for the selective detection of enantiopure spectrum is reported.
      The experiment is simple, easy to implement and provides accurate eanantiomeric
      excess in addition to the determination of the proton-proton couplings of an
      enantiomer within a short experimental time (few minutes).

PMID- 19854086
TI  - ["It's harder": nurses' experiences of caring for patients with cancer
      recurrence].
AB  - OBJECTIVE: To examine the experiences and responses of nurses caring for patients
      with recurrence of cancer. MATERIAL AND METHODS: A qualitative cross-sectional
      study based on grounded theory. Data was collected, based on semi-structured
      interviews carried out in four cancer units of two hospitals in Navarra, after
      obtaining ethical approval. The sample consisted of 14 nurses. RESULTS: Providing
      care during cancer recurrence is described as a difficult situation, even more
      than in the first diagnosis of cancer. This is because nurses have to deal with
      the loss of patient hope in treatment and the fear of the possibility of the
      patient's death. To deal with this reality, nurses try to do their best to meet
      the emotional needs of the patient, at the same time as managing barriers
      including lack of time, workload, and inadequate training in psycho-oncology.
      CONCLUSIONS: The data show the difficulty nurses have in dealing with the
      emotional care of patients with recurrence. If the Health Service commitment is
      to offer holistic care to cancer patients and their families, there should be a
      corresponding commitment towards improving nursing training in psychosocial
      issues.

PMID- 19854087
TI  - [Obstetrics-gynaecology nursing specialty (midwifery)].

PMID- 19854088
TI  - [Clinical case: Complicated grief in primary care. Care plan].
AB  - This is the case of a 61-year-old patient woman that visits her nurse in Primary
      Health Care to get the control of blood pressure and glycemia. In the last two
      years has suffered the loss of her husband and of two brothers beside having
      lived through other vital stressful events that have taken her to a situation of
      complicated grief. The care plan is realized using the M. Gordon assessment
      system and standardized languages NANDA, NOC and NIC. The principal aims were the
      improvement of the depression level and the improvement in the affliction
      resolution. As suggested interventions were proposed to facilitate the grief and
      the derivation to a mental health unit. A follow-up of the patient was realized
      in nursing consultation at Primary health care to weekly intervals, in the
      beginning, and monthly, later. The evaluation of the care plan reflects an
      improvement in the criteria of Prigerson's complicated grief; an increase of the
      recreative activities; the retreat of the mourning that still she was guarding;
      as well as an improvement in the control of the blood pressure numbers. The
      attention of nurses before a case of complicated grief turns out to be complex.
      Nevertheless the suitable accomplishment of certain interventions orientated to
      facilitating the grief, with a follow-up in consultation, shows the efficiency.
      The difficulty in the boarding of the psychosocial problems meets increased at
      the moment of are necessary the nursing diagnostics adapted for every individual
      case. The work in group between nurses could improves the consensus.

PMID- 19854089
TI  - Evaluation of the material assignment method used by a Monte Carlo treatment
      planning system.
AB  - An evaluation of the conversion process from Hounsfield units (HU) to material
      composition in computerised tomography (CT) images, employed by the Monte Carlo
      based treatment planning system ISOgray (DOSIsoft), is presented. A boundary in
      the HU for the material conversion between "air" and "lung" materials was
      determined based on a study using 22 patients. The dosimetric consequence of the
      new boundary was quantitatively evaluated for a lung patient plan.

PMID- 19854090
TI  - [Molecular imaging of tumor hypoxia].
AB  - By allowing an earlier diagnosis and a more exhaustive assessment of extension of
      the disease, the tomography by emission of positrons (TEP) transforms the care of
      numerous cancers. At present, (18)F-fluorodesoxyglucose ([(18)F]-FDG) imaging
      appears as the only one available but new molecular markers are being developed.
      In the next future they would modify the approach of cancers. In this context,
      the molecular imaging of the hypoxia and especially the (18)Ffluoromisonidazole
      TEP ([(18)F]-MISO TEP) can give supplementary information allowing the mapping of
      hypoxic regions within the tumour. Because of the links, which exist between
      tumour hypoxia and treatment resistance of very numerous cancers, this
      information can have an interest, for determination of prognosis as well as for
      the delineation, volumes to be irradiated. Head and neck tumours are doubtless
      those for which the literature gives the most elements on the therapeutic impact
      of tumour hypoxia. Targeted therapies, based on hypoxia, already exist and the
      contribution of the molecular imaging could be decisive in the evaluation of the
      impact of such treatment. Molecular imaging of brain tumours remains to be
      developed. The potential contributions of the [(18)F]-MISO TEP for the care of
      these patients need to be confirmed. In this context, we propose a review of
      hypoxia molecular imaging taking as examples head and neck tumours and
      glioblastomas (GB), two tumours for which hypoxia is one of the key factors to
      overcome in order to increase therapeutics results.

PMID- 19854091
TI  - [Quality assurance of enhanced dynamic wedge using the aS500-II, EPID].
AB  - PURPOSE: The work presented herein rests on the study of the Varian EPID aS500-II
      and the Image Acquisition system IAS3. We assessed the dosimetric performance of
      this EPID for measurements and quality assurance of enhanced dynamic wedge
      profiles and wedge factors. MATERIALS AND METHODS: We evaluated the dosimeter
      properties using the integrated asynchronous mode of acquisition in treatments
      with enhanced dynamic wedges (EDW). We studied the performance, stability and the
      reproducibility in measurements of the transmission factors and profiles of the
      fields with dynamic wedges. EPID profiles were compared to the "Profiler Sun
      Nuclear" diode array and PTW ion chamber. Analytical functions were developed in
      order to correct EDW profiles. The dependence of EPID measurements on wedge
      direction, beam dimensions and source to EPID distance was assessed. RESULTS: The
      backscatter produced by the "exact arm" was evaluated; EPID profiles depended on
      the EDW direction and on the detector source distance. Wedge factors were
      determined using this detector and compared to the ion chamber response,
      differences were all within 1 %. Two empirical correction functions were
      developed to produce EPID wedge profiles that correspond to diode for all wedge
      angles and energies depending on the wedge direction. CONCLUSION: The EPID is
      highly suited to regular measurement of EDW due to the reproducibility of the
      EPID-measured wedge factors and profiles.

PMID- 19854092
TI  - [Definitive treatment of anal canal carcinoma with radiotherapy: adverse impact
      of a pre-radiation resection. A retrospective study of 57 patients treated with
      curative intent].
AB  - PURPOSE: To describe retrospectively the overall survival, the cancer specific
      survival and the tumor control in an homogeneous series of patients with
      epidermoid carcinoma of the anal canal treated with definitive radiotherapy; to
      assess the impact of brachytherapy, chemotherapy and pre-radiotherapy resection
      on the risk of recurrence. PATIENTS AND METHODS: From 1997 to 2007, 57 patients
      (pts) presenting with an epidermoid carcinoma of the anal canal (T1: 14, T2: 33,
      T3-4: 10, N0: 31, N1: 19, N2: 3, N3: 4, M0: 57) were treated with definitive
      radiotherapy by the same radiation oncologist. The treatment included an external
      beam irradiation (EBRT) given to the posterior pelvis (45Gy/25 fractions) and,
      six weeks later, a boost delivered with interstitial brachytherapy (37/57) or
      external beam irradiation (20/57). Twelve pts had undergone a surgical resection
      of the tumour before radiotherapy. A belly board was used for EBRT in 13 pts. A
      concurrent platinum based chemotherapy was done in 42 pts. The mean follow-up was
      57 months. RESULTS: The overall survival rate at 5 years was 89% with a cause
      specific survival of 96%. Five patients recurred (5-year rate: 12%: four had
      local relapse (5-year rate: 8%), four had groin recurrence, and distant
      metastases were seen in two. In univariate analysis, the risk of relapse was
      higher in patients who had undergone a pre-radiation excision (p=0.018), in those
      who did not receive chemotherapy (p=0.076) and in those who were irradiated on a
      belly board (p=0.049). In multivariate analysis, a pre-radiotherapy resection
      (p=0.084) had an inverse impact on the tumour control reaching the level of
      statistical significance and the use of a belly board was of marginal influence
      (p=0.13). CONCLUSION: Radiotherapy and chemoradiation with cisplatine-based
      chemotherapy cure a vast majority of patients with epidermoid carcinoma of the
      anal canal. Therapeutic factors that may interfere with the definition of the
      target volume and the patients' repositioning may decrease the efficacy of
      radiotherapy. Pre-radiotherapy surgical resection should be avoided.

PMID- 19854093
TI  - [Evaluation of a new table, Exact IGRT(Varian), on the treatment beam attenuation
      and the image quality].
AB  - PURPOSE: A new couch top designed for IGRT procedures, Exact IGRT (EIC), has been
      developped. It has the advantage of having no removable support bars and is
      thicker than a standard table (Exact(EC)) in order to create the appropriate
      rigidity. The aim of this study was to quantify the beam attenuation caused by
      the EIC and to evaluate the EIC contribution to on-board image quality
      improvement. MATERIALS AND METHODS: The treatment beam attenuation and the
      surface-dose of the patient were measured for simple radiation geometries at
      different gantry angles and for two clinical cases, head and neck and posterior
      pelvis. The 2D and 3D image quality was analysed. RESULTS: The beam attenuation
      at 215 degrees was 2.0% to 4.1% for 6 MV and 1.2% to 2.2% for 18 MV according to
      the EIC part. The dose-surface tripled between the measurement without table and
      with table into the beam (similar results between EIC and EC). The EIC influence
      was significative for the posterior pelvic tumor, acceptable for the head and
      neck case. The EIC showed a clear improvement of the low contrast resolution
      (visualisation of a 7mm and 1% contrast disk [15mm for the EC]). CONCLUSION: In
      order to take into account the beam attenuation, the EIC should be modeled in the
      treatment planning system. However, the good quality of 3D images obtained with
      the EIC allows us to easily visualize soft tissues.

PMID- 19854094
TI  - Radiological stab wound channel depiction with instillation of contrast medium.
AB  - The radiological depiction of stab wounds in soft-tissues using multislice
      computed tomography is difficult and the hereby obtained images often lack
      contrast. To overcome these shortcomings we tried a new method. We gently
      instilled the contrast medium Lipiodol((R)) Ultra-fluide into five experimentally
      induced stab wounds on a pork haunch. Subsequent MSCT reconstructions of the
      wounds delivered clear, for medical laymen easily appreciable images regarding
      the stab direction and the stab depth. We believe that this easy and rapid
      technique can be useful in the examination of stab wounds in living and dead
      victims of sharp trauma.

PMID- 19854095
TI  - The LRRK2 G2385R variant is a risk factor for sporadic Parkinson's disease in the
      Korean population.
AB  - The G2385R (SNP accession no. rs34778348) and R1628P (rs33949390) variants of
      leucine-rich repeat kinase 2 (LRRK2, PARK8) are emerging as an important risk
      factor for Parkinson's disease (PD) in the ethnic Chinese and Japanese
      populations. The purpose of this study was to investigate whether these variants
      are a genetic risk factor in sporadic PD patients in the Korean population. A
      total of 923 patients and 422 healthy subjects were included. The variants were
      screened by a SNaPshot assay. The LRRK2 G2385R variant was detected in 82 PD
      patients (8.9%, two homozygous and 80 heterozygous) and in 21 normal controls
      (5.0%, all heterozygous). The frequency of the LRRK2 G2385R variant in PD was
      significantly higher than in normal controls (adjusted odds ratio 1.83, p =
      0.0170, 95% confidence interval 1.11-3.00). There were no differences in the mean
      age at onset or gender between the G2385R carriers and the non-carriers in PD
      patients. The LRRK2 R1628P variant was very rare (0.78% in patients versus 0.26%
      in controls) in the tested 384 patient-control pairs, and was not a significant
      risk factor. This study supports that the LRRK2 G2385R variant may be a genetic
      risk factor for sporadic PD in the Korean population.

PMID- 19854096
TI  - Practice and ethnic variations in avoidable hospital admission rates in
      Christchurch, New Zealand.
AB  - Using hospital admissions data for 2005-2007 this paper examines variations in
      avoidable hospital admission rates between general practitioner surgeries in
      Christchurch, New Zealand. There is a substantial variation in rates between
      surgeries which largely reflects the influence of material deprivation and also
      the independent effect of ethnicity. By contrast, other quantitative measures of
      primary care provision were insignificant. There was also a wide variation
      between practices in the uptake of Care Plus funding for patients with chronic
      conditions. Practice deprivation, ethnicity and age only explained a minor part
      of this variation. The findings suggest a need for possible strategies, in
      particular a greater targeting of funding to high risk patients in more deprived
      practices, to reduce hospitalisation. The wide variability in general practice
      use of hospital services needs further study to identify possible individual and
      contextual explanations.

PMID- 19854097
TI  - Actin and microtubule cytoskeleton interactions.
AB  - Plant cytoskeleton consists of two major networks of protein polymers, actin
      microfilaments (AFs) and microtubules (MTs). These networks perform numerous
      functions that are essential for cell division and for maintaining the integrity
      of cytoplasm required for intracellular transport and cell shape. Besides the
      more or less indirect cooperation between AFs and MTs, their direct interactions
      through specific physically interacting proteins has been well described in
      yeast, nematodes, insect and animal cells. Recently, promising candidates for
      corresponding homologous proteins have been identified in plants, although there
      is still lack of functional evidence for these interactions. Here we summarize
      recent advances in our knowledge about the candidate proteins or protein
      complexes that interact with both AFs and MTs and their role in fundamental
      cellular and developmental processes.

PMID- 19854098
TI  - Transport vesicle formation in plant cells.
AB  - In protein trafficking, transport vesicles bud from donor compartments and carry
      cargo proteins to target compartments with which they fuse. Thus, vesicle
      formation is an essential step in protein trafficking. As for mammals, plant
      cells contain the three major types of vesicles: COPI, COPII, and CCV and the
      major molecular players in vesicle-mediated protein transport are also present.
      However, plant cells generally contain more isoforms of the coat proteins, ARF
      GTPases and their regulatory proteins, as well as SNAREs. In addition, plants
      have established some unique subfamilies, which may reflect plant cell-specific
      conditions such as the absence of an ER-Golgi intermediate compartment and the
      combined activities of the TGN and early endosome. Thus, even though we are still
      at an early stage in understanding the physiological function of these proteins,
      it is already clear that vesicle-mediated protein transport in plant cells
      displays both similarities as well as differences in animal cells.

PMID- 19854100
TI  - Quantum chemical calculations to reveal the relationship between the chemical
      structure and the fluorescence characteristics of phenylquinolinylethynes and
      phenylisoquinolinylethynes derivatives, and to predict their relative
      fluorescence intensity.
AB  - In this paper the relationship between the chemical structure and fluorescence
      characteristics of 30 phenylquinolinylethyne (PhQE), and
      phenylisoquinolinylethyne (PhIE) derivatives compounds employing ab initio
      calculations have been elucidated. Quantum chemical calculations (6-31G) were
      carried out to obtain: the optimized geometry, energy levels, charges and dipole
      moments of these compounds, in the singlet (steady and excited states) and
      triplet states. The relationship between quantum chemical descriptors, and
      wavelength of maximum excitation and emission indicated that these two parameters
      have the most correlation with quantum chemical hardness (eta). Also, stokes
      shift has the most correlation with the square of difference between the maximum
      of positive charges in the singlet steady and singlet excited states. The
      quantitative structure-property relationship (QSPR) of PhQE and PhIE was studied
      for relative fluorescence intensity (RFI). The genetic algorithm (GA) was applied
      to select the variables that resulted in the best-fit models. After the variable
      selection, multiple linear regression (MLR) and support vector machine (SVM) were
      both utilized to construct linear and non-linear QSPR models, respectively. The
      SVM model demonstrated a better performance than that of the MLR model. The route
      mean square error (RMSE) in the training and the test sets for the SVM model was
      0.195 and 0.324, and the correlation coefficients were 0.965 and 0.960,
      respectively, thus revealing the reliability of this model. The resulting data
      indicated that SVM could be used as a powerful modeling tool for QSPR studies.
      According to the best of our knowledge, this is the first research on QSPR
      studies to predict RFI for a series of PhQE and PhIE derivative compounds using
      SVM.

PMID- 19854099
TI  - Signals of growth regulation in bacteria.
AB  - A fundamental characteristic of cells is their ability to regulate growth in
      response to changing environmental conditions. This review focuses on recent
      progress toward understanding the mechanisms by which bacterial growth is
      regulated. These phenomena include the 'viable but not culturable' (VBNC) state,
      in which bacterial growth becomes conditional, and 'persistence', which confers
      antibiotic resistance to a small fraction of bacteria in a population. Notably,
      at least one form of persistence appears to involve the generation of nongrowing
      phenotypic variants after transition through stationary phase. The possible roles
      of toxin-antitoxin modules in growth control are explored, as well as other
      mechanisms including contact-dependent growth inhibition, which regulates
      cellular metabolism and growth through binding to an outer membrane protein
      receptor.

PMID- 19854102
TI  - Neurophysiological changes with age probed by inverse modeling of EEG spectra.
AB  - OBJECTIVE: To investigate age-associated changes in physiologically-based EEG
      spectral parameters in the healthy population. METHODS: Eyes-closed EEG spectra
      of 1498 healthy subjects aged 6-86 years were fitted to a mean-field model of
      thalamocortical dynamics in a cross-sectional study. Parameters were
      synaptodendritic rates, cortical wave decay rates, connection strengths (gains),
      axonal delays for thalamocortical loops, and power normalizations. Age trends
      were approximated using smooth asymptotically linear functions with a single
      turning point. We also considered sex differences and relationships between model
      parameters and traditional quantitative EEG measures. RESULTS: The cross
      sectional data suggest that changes tend to be most rapid in childhood, generally
      leveling off at age 15-20 years. Most gains decrease in magnitude with age, as
      does power normalization. Axonal and dendritic delays decrease in childhood and
      then increase. Axonal delays and gains show small but significant sex
      differences. CONCLUSIONS: Mean-field brain modeling allows interpretation of age
      associated EEG trends in terms of physiological processes, including the growth
      and regression of white matter, influencing axonal delays, and the establishment
      and pruning of synaptic connections, influencing gains. SIGNIFICANCE: This study
      demonstrates the feasibility of inverse modeling of EEG spectra as a noninvasive
      method for investigating large-scale corticothalamic dynamics, and provides a
      basis for future comparisons.

PMID- 19854101
TI  - Emergent US adenovirus 3 strains associated with an epidemic and serious disease.
AB  - BACKGROUND: Adenovirus type 3 (HAdV3) is one of the most prevalent serotypes
      detected globally. Variants of HAdV3 have been associated with outbreaks of
      severe disease. OBJECTIVES: To better understand genetic diversity of circulating
      HAdV3s and examine risk factors for severe disease. STUDY DESIGN: Restriction
      enzyme analysis for genomic characterization of clinical HAdV3 isolates detected
      by 15 collaborative US laboratories during the period July 2004 to May 2007.
      Multivariate modeling was employed for statistical analyses. RESULTS: The most
      common HAdV3 types of 516 isolates studied were HAdV3a2 (36.9%), HAdV3a50
      (27.1%), HAdV3a51 (18.0%), and HAdV3a17 (4.6%). Non-HAdV3a genome types were rare
      (1.2%). HAdV3a50 and HAdV3a51 are newly described variants which became more
      prevalent in 2006 and 2007 and have been associated with at least one epidemic.
      Their uniqueness was determined by specific banding profiles generated by digests
      with endonucleases BclI, BglII, and HindIII. Multivariable risk factor modeling
      demonstrated that children under 2 years of age (OR=2.7; 95%CI 1.6-4.6), persons
      with chronic disease (OR=5.1; 95%CI 2.6-9.8), persons infected with HAdV3a2
      (OR=3.0; 95%CI 1.5-6.0), with HAdV3a50 (OR=2.5; 95%CI 1.2-5.2), or with multiple
      or rare strains (OR=2.8; 95%CI 1.3-6.5) were at increased risk of severe HAdV3
      clinical disease. CONCLUSIONS: In the study period considerable genetic diversity
      was found among US clinical HAdV3 strains. Novel variants emerged and became
      prevalent. One such emergent strain may be associated with more severe clinical
      disease.

PMID- 19854103
TI  - A patient with a transient photomyogenic response.

PMID- 19854104
TI  - Cloacal exstrophy: a comprehensive review of an uncommon problem.
AB  - OBJECTIVE: To provide a comprehensive overview of the clinical features,
      diagnosis, current management strategies, and outcomes of cloacal exstrophy.
      METHODS: A PUBMED/Medline search of the literature was performed on cloacal
      exstrophy focusing on associated anomalies, treatment, and quality of life
      issues. RESULTS: The incidence of cloacal exstrophy is between 1 in 200,000 and
      400,000 live births. Survival rates now approach 100% secondary to improved
      understanding of underlying abnormalities and advances in neonatal care and
      surgical technique. Important principles of initial management include proper
      nutritional support, early closure of exstrophy, and preservation of intestinal
      length. The achievement of urinary and fecal continence remains a challenge. Data
      for long-term outcomes are now emerging which provide new insight into issues of
      gender identity, function, and psychosocial development of these patients.
      CONCLUSION: Cloacal exstrophy remains a rare and complex congenital anomaly,
      characterized by an array of anatomical defects affecting multiple organ systems.
      A multidisciplinary approach to management is advocated with a focus on
      optimization of patient function and quality of life.

PMID- 19854105
TI  - Management of major blunt pediatric renal trauma: single-center experience.
AB  - OBJECTIVE: To review the impact of major pediatric renal trauma and its
      management on long-term function and morphology of the injured kidney. METHODS:
      Thirty-six blunt trauma patients (20 males, 16 females) presented in 2004-2007
      (age range 2 days to 14 years; mean 6.2 years). Thirty-seven renal units were
      included: 13 grade III, 14 grade IV, and 10 grade V injuries. Follow up was for 3
      38 (mean 14) months. Patients were managed non-operatively unless vitally
      unstable. The most common causes of trauma were motor vehicle accidents and
      falls. Fourteen patients had associated non-renal injuries. Four patients had pre
      existing renal problems. RESULTS: The surgical intervention group (13 patients,
      36%) included 9/10 grade V and 4/14 grade IV renal injuries. Surgical repair of
      lacerations was performed in seven cases, partial nephrectomy in four cases and
      nephrectomy in two cases. Follow up showed no significant change in renal
      function, and none developed hypertension. The non-operative group (24 patients,
      63.2%) included all grade III injuries, 10 grade IV injuries, and one grade V
      injury. There was an excellent outcome for 18/24 patients (75%) with kidney
      preservation, no complications from urinary extravasation and hematoma
      resolution. The remaining patients had lower polar infarction (1), renal atrophy
      (1), persistent subcapsular collection (2), recurrent hematuria requiring
      angioembolization (1), and there was one death related to central nervous system
      injury. CONCLUSION: The outcome of our management of pediatric major renal trauma
      was favorable overall. Longer follow up is needed with regard to renal function
      and development of hypertension.

PMID- 19854106
TI  - Essential and synergistic roles of IL1 and IL6 in human Th17 differentiation
      directed by TLR ligand-activated dendritic cells.
AB  - Requirements for human Th17 differentiation in the context of activated dendritic
      cells (DCs) are still emerging. Here, we demonstrate that several Toll-like
      receptor (TLR) ligands, particularly LPS and a synthetic lipoprotein, activate
      human DCs to direct increased human Th17 differentiation. Based on neutralization
      studies, IL1, IL6, and TGFbeta contributed to human Th17 differentiation induced
      by LPS-activated DCs. Furthermore, TLR ligand-activated DCs produced high levels
      of IL6 and low levels of IL1beta. In an antigen presenting cell (APC)-free
      system, the minimum requirements identified for human Th17 differentiation from
      adult naive CD4(+) T cells, depleted of CD25(+) cells, were TGFbeta and high
      levels of IL1beta. However, in the presence of the physiologically low levels of
      IL1 such as those produced by DCs, both TGFbeta and IL6 were also essential.
      These results help to explain the conflicting reports in the literature on the
      roles of IL1 and IL6 on human Th17 differentiation.

PMID- 19854107
TI  - Pathological assessment of intrauterine growth restriction.
AB  - Intrauterine growth restriction (IUGR) is a major cause of foetal and neonatal
      morbidity and mortality. During post mortem, the pathologist is well placed to
      diagnose the presence and cause of IUGR in a stillborn baby. This article
      describes the approach of the pathologist in diagnosing IUGR and some of the
      pitfalls. We distinguish between reduced growth potential (formerly symmetrical
      IUGR) and nutritional IUGR (formerly asymmetrical IUGR). Aetiologically,
      restricted growth can be of foetal, maternal and placental origin. We discuss the
      importance of identifying the cause of IUGR in a clinicopathological context and
      the pathological findings in some of the more frequent causes of IUGR presenting
      at post mortem. Based on an accurate gestational age, ideally determined by the
      obstetrician in early pregnancy, the pathologist can derive a birth weight
      centile. However, the pathologist is also able to identify other indicators of
      IUGR, such as an elevated brain/liver weight ratio, atrophic thymus and changes
      in other internal organs. Placental examination plays a major role in the
      investigation as the majority of IUGR cases have significant placental pathology.
      This includes pre-eclampsia-related changes, abnormalities of the villous
      parenchyma and pathology of the umbilical cord. The potential benefit of a
      meticulous workup of IUGR foetuses is to provide an explanation of the
      pathological condition and to identify avoidable causes.

PMID- 19854108
TI  - Correlation between memory, proton magnetic resonance spectroscopy, and
      interictal epileptiform discharges in temporal lobe epilepsy related to mesial
      temporal sclerosis.
AB  - OBJECTIVE: The aim of the study described here was to examine the relationship
      between memory function, proton magnetic resonance spectroscopy ((1)H-MRS)
      abnormalities, and interictal epileptiform discharge (IED) lateralization in
      patients with temporal lobe epilepsy (TLE) related to unilateral mesial temporal
      sclerosis. METHODS: We assessed performance on tests of memory function and
      intelligence quotient (IQ) in 29 right-handed outpatients and 24 controls. IEDs
      were assessed on 30-minute-awake and 30-minute-sleep EEG samples. Patients had
      (1)H-MRS at 1.5 T. RESULTS: There was a negative correlation between IQ (P=0.031)
      and Rey Auditory Verbal Learning Test results (P=0.022) and epilepsy duration;
      between(1)H-MRS findings and epilepsy duration (P=0.027); and between N
      acetylaspartate (NAA) levels and IEDs (P=0.006) in contralateral mesial temporal
      structures in the left MTS group. (1)H-MRS findings, IEDs, and verbal function
      were correlated. CONCLUSIONS: These findings suggest that IEDs and NAA/(Cho+Cr)
      ratios reflecting neural metabolism are closely related to verbal memory function
      in mesial temporal sclerosis. Higher interictal activity on the EEG was
      associated with a decline in total NAA in contralateral mesial temporal
      structures.

PMID- 19854109
TI  - Factors that affect interictal cardiovascular autonomic dysfunction in temporal
      lobe epilepsy: role of hippocampal sclerosis.
AB  - The aim of this study was to evaluate possible factors affecting interictal
      cardiovascular autonomic function in temporal lobe epilepsy with complex partial
      seizures, paying special attention to hippocampal sclerosis. The study was
      carried out with 88 patients with epilepsy (22 with left hippocampal sclerosis,
      22 with right hippocampal sclerosis, and 44 without hippocampal sclerosis) and 44
      healthy subjects. All subjects underwent three tests of cardiac autonomic
      function: heart rate variation during resting activity, heart rate variation in
      response to deep breathing and blood pressure response to rising quickly from the
      supine position. Hippocampal sclerosis and disease duration were found to have
      significantly important effects on parasympathetic autonomic function, whereas
      seizure control and type of antiepileptic drug had significant effects on
      sympathetic autonomic function. This study shows that in addition to factors
      related to the chronic nature of epilepsy and antiepileptic drug use, hippocampal
      sclerosis may cause autonomic dysfunction during the interictal period in persons
      with temporal lobe epilepsy.

PMID- 19854110
TI  - Commentary on Bonnier P. L'aschematie. Rev Neurol (Paris) 1905;13:605-9.

PMID- 19854111
TI  - The impact of social support on health related quality of life in persons with
      epilepsy.
AB  - Previous studies have found that psychosocial factors have the greatest impact on
      health-related quality of life (HRQOL). Social support can buffer the negative
      impact of stressful events and chronic health conditions. To date, no population
      studies have examined the association between social support and epilepsy. In the
      2003 California Health Interview Survey (CHIS), four questions were used to
      assess social support. A set of survey weight-adjusted logistic regression
      analyses were conducted with self-rated health status as the outcome. In those
      regression models, we examined the effect of epilepsy status, social support, and
      their interactions, after controlling for demographics. Analyses examining the
      interaction between epilepsy and social support showed a significant interaction
      between epilepsy and "availability of someone to love you and make you feel
      wanted." Once demographics were controlled for, persons without epilepsy and poor
      affectionate support reported fair/poor self-rated health status (odds
      ratio=1.7). Persons with epilepsy and good affectionate support also reported
      fair/poor self-rated health status (odds ratio=3.3). Persons with epilepsy and
      poor affectionate support were the most likely to report fair/poor self-rated
      health status (odds ratio=9.1). Persons with epilepsy need encouragement to
      actively seek and sustain supportive personal relationships that may help improve
      their quality of life.

PMID- 19854112
TI  - Antiseizure effects of 3alpha-androstanediol and/or 17beta-estradiol may involve
      actions at estrogen receptor beta.
AB  - Testosterone (T), the principal androgen secreted by the testes, can have
      antiseizure effects. Some of these effects may be mediated by T's metabolites. T
      is metabolized to 3alpha-androstanediol (3alpha-diol). T, but not 3alpha-diol,
      binds androgen receptor. We investigated effects of 3alpha-diol (1 mg/kg, SC)
      and/or an androgen receptor blocker (flutamide 10 mg, SC), 1 hour prior to
      administration of pentylenetetrazol (85 mg/kg, IP). Juvenile male rats
      administered 3alpha-diol had less seizure activity than those administered
      vehicle. Flutamide had no effects. T is aromatized to 17beta-estradiol (E(2)),
      which, like 3alpha-diol, acts at estrogen receptors (ERs). Selective estrogen
      receptor modulators that favor ERalpha (propyl pyrazole triol, 17alpha-E(2)) or
      ERbeta (diarylpropionitrile, coumestrol, 3alpha-diol), or both (17beta-E(2)),
      were administered (0.1 mg/kg, SC) to juvenile male rats 1 hour before
      pentylenetetrazol. Estrogens with activity at ERbeta, but not those selective for
      ERalpha, produced antiseizure effects. Actions at ERbeta may underlie some
      antiseizure effects of T's metabolites.

PMID- 19854113
TI  - Postpartum depression in women with epilepsy: influence of antiepileptic drugs in
      a prospective study.
AB  - Patients with epilepsy are at high risk for major depressive disorder (MDD) and,
      according to one report, postpartum depression (PPD) as well. The study described
      here sought to determine the prevalence and risk factors for PPD among women with
      epilepsy. Fifty-six women with epilepsy participating in a prospective study of
      perinatal antiepileptic drug (AED) pharmacokinetics were included. Participants
      completed the Beck Depression Inventory (BDI) during pregnancy and the postpartum
      period. Fourteen participants (25.0%) had a postnatal BDI score > or =12
      indicative of PPD. Logistic regression indicated that significant risk factors
      for PPD among women with epilepsy included multiparity (odds ratio=12.5) and AED
      polytherapy (odds ratio=9.3). The rate of PPD was unaffected by the use of
      specific AEDs. In conclusion, PPD rates are higher among women with epilepsy than
      the general population, particularly those who are multiparous or receiving AED
      polytherapy, and there is no evidence that AED selection modifies this risk.

PMID- 19854114
TI  - Preliminary results with accelerated partial breast irradiation in high-risk
      breast cancer patients.
AB  - PURPOSE: To analyze prognostic factors in adequately staged breast cancer
      patients who were treated with accelerated partial breast irradiation (APBI).
      METHODS AND MATERIALS: Axillary staging was required for invasive carcinomas.
      Between February 2003 and June 2009, 204 women with early stage breast carcinomas
      were treated with APBI using multicatheter, MammoSite, or Contura brachytherapy
      to 34 Gy in 10 fractions 2 times per day. Six patient characteristics were
      examined for prognostic significance: (1) N stage, (2) estrogen receptor (ER)
      status, (3) histologic subtype, (4) margin status, (5) age, and (6) tumor size.
      The median followup was 22 months. RESULTS: There were three failures in the
      ipsilateral breast (all were elsewhere failures), one relapse in the axilla, and
      seven relapses at any site. The presence of positive axillary node(s) had a
      significant adverse effect on ipsilateral breast tumor control (p=0.045) and
      locoregional control (p=0.001). The presence of an ER (-) tumor had a significant
      adverse effect on relapse-free survival (p=0.04). CONCLUSIONS: The patients with
      positive axillary node(s) were at increased risk for failure elsewhere in the
      ipsilateral breast or axilla, and the patients with ER (-) tumors were at
      increased risk for relapse at any site. However, it is unclear whether the pN1
      and ER (-) patients would have faired any better if they had received whole
      breast irradiation rather than APBI. We believe that the patients with positive
      axillary node(s) or ER (-) tumors should be treated on clinical trials to better
      define the role of APBI.

PMID- 19854115
TI  - Electrochemical and AFM characterization on gold and carbon electrodes of a high
      redox potential laccase from Fusarium proliferatum.
AB  - The redox potential of the T1 copper site of laccase from Fusarium proliferatum
      was determined by titration to be about 510 mV vs. SCE (750 mV vs. NHE), which
      makes it a high redox potential enzyme. Anaerobic electron transfer reactions
      between laccase and carbon and gold electrodes were detected, both in solution
      and when the enzyme was adsorbed on these surfaces. In solution, a single high
      potential signal (660 mV vs. SCE) was recorded at the carbon surfaces,
      attributable to the T1 copper site of the enzyme. However, a well-defined
      oxidative process at about 660 mV and an anodic wave at 350 mV vs. SCE were
      recorded at the gold electrode, respectively associated with the T1 and T2 copper
      sites. Laccase-modified carbon electrodes behaved analogously when the enzyme was
      in solution, unlike laccase adsorbed on gold, which showed only a low-potential
      signal. Laccase molecules were successfully imaged by AFM; obtaining a thick
      compact stable film on Au(111), and large aggregates forming a complex network of
      small branches leaving voids on the HOPG surface. Laccase-modified carbon
      electrodes retained significant enzymatic activity, efficiently oxidising
      violuric acid and reducing molecular oxygen. Explanations are proposed for how
      protein-film organisation affects the electrode function.

PMID- 19854116
TI  - Validation of a MLC method with fluorescence detection for the determination of
      quinolones in urine samples by direct injection.
AB  - A sensitive and robust method was developed and validated for the routine
      identification and quantification of five quinolones in urine samples directly
      injected into a micellar liquid chromatographic system without any pre-treatment
      step. Since the simultaneous elution of the five compounds was not resolved, two
      mobile phases have been proposed: (a) for ciprofloxacin and levofloxacin 0.15M
      sodium dodecyl sulphate, 12.5% propanol and 0.5% triethylamine at pH 3.0 as the
      mobile phase and the detector at excitation wavelength 285 nm and emission
      wavelength 465 nm; and (b) for lomefloxacin, ofloxacin and moxifloxacin 0.05 M
      sodium dodecyl sulphate, 12.5% propanol and 0.5% triethylamine at pH 3.0 as the
      mobile phase and the detector at excitation wavelength 295 nm and emission
      wavelength 485 nm. Using these conditions, and in accordance with the food and
      drug analysis (FDA) guideline, the limit of quantification was 1 ng/mL, and the
      relative standard deviation and accuracy of the inter-day assay were 1.0-8.4% and
      0.11-1.5%, respectively. Detection of the urinary excretion of four quinolones
      was followed up at 12h after the healthy volunteers had taken the drug. No
      potential interference from metabolites was observed. This procedure permits the
      rapid and reproducible measurement of low levels of quinolones in a small amount
      of urine.

PMID- 19854117
TI  - Development of a high-performance liquid chromatographic-mass spectrometric
      method for the determination of cellular levels of the tyrosine kinase inhibitors
      lapatinib and dasatinib.
AB  - A highly sensitive and selective liquid chromatography tandem mass spectrometry
      (LC-MS/MS) method has been developed to quantify cellular levels of the tyrosine
      kinase inhibitors (TKIs) dasatinib (Sprycel) and lapatinib (Tykerb, Tyverb).
      Cellular samples were extracted with a tert-butyl methyl ether:acetonitrile (3:1,
      v/v):1 M ammonium formate pH 3.5 (8:1, v/v) mixture. Separation was achieved on a
      Hyperclone BDS C18 (150 mm x 2.0 mm 3 microm) column with isocratic elution using
      a mobile phase of acetonitirile-10 mM ammonium formate, pH 4 (54:46, v/v), at a
      flow rate of 0.2 mL/min. The TKIs were quantified using a triple quadrupole mass
      spectrometer which was operated in multi-reaction-monitoring mode employing
      positive electrospray ionisation. The limit of detection and limit of
      quantification for lapatinib was determined to be 15 and 31 pg on column,
      respectively. The limit of detection and quantification for dasatinib was 3 and
      15 pg on column, respectively. The method allowed for sensitive and accurate
      determination of cellular levels of dasatinib and lapatinib. In addition, we
      examined the potential for this method to be utilised to quantitate other TKIs,
      using gefitinib, erlotinib, imatinib and sorafenib as examples. In principle,
      these agents were also quantifiable by this method, however, no drug specific
      validation studies were undertaken with these TKIs. The data indicates that in
      the cancer cell-line model, DLKP, significantly more lapatinib accumulates in
      cells in comparison to dasatinib. Additionally, over-expression of the membrane
      protein drug transporter, P-glycoprotein (P-gp) a common cancer drug resistance
      mechanism, greatly reduces the cellular accumulation of dasatinib but not of
      lapatinib.

PMID- 19854118
TI  - Rapid and simple method for determination of cephradine in human plasma using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS): application to the
      bioequivalence study.
AB  - A rapid and simple procedure was developed for the determination of cephradine in
      human plasma using liquid chromatography coupled with electrospray ionization
      tandem mass spectrometry (LC-ESI-MS/MS). After trichloroacetic acid (TCA)
      precipitation of proteins from plasma samples, cephradine and cefaclor (the
      internal standard; IS) were eluted on a CN column. The isocratic mobile phase
      used consisted of acetonitrile-water-formic acid (25:75:0.1, v/v/v). Cephradine
      and the IS were both detected in multiple reaction monitoring (MRM) mode at the
      transitions: m/z 350.0 --> 90.8 for cephradine and m/z 368.1 --> 106.0 for the
      IS, respectively. The calibration curve was linear over the concentration range
      from 0.05 to 50 microg/ml, and correlation coefficients were greater than 0.996.
      The coefficient of variation of assay precision was less than 9.36%, and its
      accuracy ranged from 87.92% to 111.16%. The chromatographic run time for each
      plasma sample was less than 3 min. The developed method was successfully applied
      to a bioequivalence study of cephradine in healthy male volunteers.

PMID- 19854120
TI  - Putting teeth in CHIP: 1997-2009 retrospective of congressional action on
      children's oral health.
AB  - When Congress reenacted the Child Health Insurance Program (CHIP) in 2009, it
      incorporated a range of dental provisions that had not been considered when the
      program was initiated in 1997. This paper posits that this change evidences the
      establishment of pediatric oral health as a distinct policy issue within
      Congressional deliberations. During this period, the US Congress received impetus
      for action on behalf of children's oral health from multiple streams of activity:
      the Surgeon General's Report, Oral Health in America, policies enacted by states,
      advocacy by the professions, promotion by policy groups, attention by the press,
      and actions of federal agencies. The death of 12-year-old Deamonte Driver appears
      to have created a tipping point for action that dovetailed with Congressional
      need to reauthorize CHIP. Federal legislative policymaking is a complex process
      that frequently builds on an issue that has emerged as timely and relevant.
      Although much remains to be done, children's oral health, cast as a public policy
      issue of import, is one such idea that appears to have gained traction among
      members of Congress.

PMID- 19854119
TI  - A randomized controlled community-based trial to improve breastfeeding rates
      among urban low-income mothers.
AB  - OBJECTIVE: The purpose of this study was to assess whether providing a
      breastfeeding support team results in higher breastfeeding rates at 6, 12, and 24
      weeks postpartum among urban low-income mothers. METHODS:  DESIGN: A randomized
      controlled trial with mother-infant dyads recruited from 2 urban hospitals.
      PARTICIPANTS: Breastfeeding mothers of full-term infants who were eligible for
      Special Supplemental Nutrition Program for Women, Infants, and Children (n=328)
      were randomized to intervention (n=168) or usual-care group (n=160).
      INTERVENTION: The 24-week intervention included hospital visits by a
      breastfeeding support team, home visits, telephone support, and 24-hour pager
      access. The usual-care group received standard care. OUTCOME MEASURE:
      Breastfeeding status was assessed by self-report at 6, 12, and 24 weeks
      postpartum. RESULTS: There were no differences in the sociodemographic
      characteristics between the groups: 87% were African American, 80% single, and
      51% primiparous. Compared with the usual-care group, more women reported
      breastfeeding in the intervention at 6 weeks postpartum, 66.7% vs 56.9% (odds
      ratio, 1.71; 95% confidence interval, 1.07-2.76). The difference in rates at 12
      weeks postpartum, 49.4% vs 40.6%, and 24 weeks postpartum, 29.2% vs 28.1%, were
      not statistically significant. CONCLUSIONS: The intervention group was more
      likely to be breastfeeding at 6 weeks postpartum compared with the usual-care
      group, a time that coincided with the most intensive part of the intervention.

PMID- 19854121
TI  - Addressing children's oral health in the new millennium: trends in the dental
      workforce.
AB  - Oral Health in America: A Report of the Surgeon General (SGROH) and National Call
      to Action to Promote Oral Health outlined the need to increase the diversity,
      capacity, and flexibility of the dental workforce to reduce oral health
      disparities. This paper provides an update on dental workforce trends since the
      SGROH in the context of children's oral health needs. Major challenges remain to
      ensure a workforce that is adequate to address the needs of all children. The
      dentist-to-population ratio is declining while shortages of dentists continue in
      rural and underserved communities. The diversity of the dental workforce has only
      improved slightly, and the the diversity of the pediatric population has
      increased substantially. More pediatric dentists have been trained, and dental
      educational programs are preparing students for practice in underserved areas,
      but the impact of these efforts on underserved children is uncertain. Other
      workforce developments with the potential to improve children's oral health
      include enhanced training in children's oral health for general dentists,
      expanded scope of practice for allied dental health professionals, new dental
      practitioners including the dental health aid therapist, and increased engagement
      of pediatricians and other medical practitioners in children's oral health. The
      evidence for increasing caries experience in young children points to the need
      for continued efforts to bolster the oral health workforce. However, workforce
      strategies alone will not be sufficient to change this situation. Requisite
      policy changes, educational efforts, and strong partnerships with communities
      will be needed to effect substantive changes in children's oral health.

PMID- 19854123
TI  - How to give a good talk.
AB  - We depend on talks to communicate our work, and we spend much of our time as
      audience members in talks. However, few scientists are taught the well
      established principles of giving good talks. Here, I describe how to prepare,
      present, and answer questions in a scientific talk. We will see how a talk
      prepared with a single premise and delivered with good eye contact is clear and
      enjoyable.

PMID- 19854122
TI  - How physicians caring for adult patients presenting with a chronic mental illness
      take into account the difficulties experienced by the children of those patients:
      preliminary study.
AB  - AIMS: To study how physicians caring for adult patients presenting a chronic
      mental disturbance take account of the difficulties of their patients' children
      under 18. METHOD: Exploratory and qualitative study based on an in-depth study of
      interviews. STUDY POPULATION: Thirteen physiatrists or neurologists following
      brain-damaged patients and 12 psychiatrists following patients with chronic
      psychiatric disorders. RESULTS: In the two groups of physicians, diversified
      practices in catering for the issues of the patient's parenthood, child-parent
      relationships, and difficulties experienced by the child. The child's
      difficulties are not approached as such. For many of the physicians,
      representations of the parenting function, and of the child's needs and
      difficulties are not often used in work with the patient. Patient-centred care
      appears at odds with catering for the patient's children and their specific
      difficulties. The seriousness of the mental pathologies, their chronic nature,
      and the fact that they can affect the patient in his/her parental functioning and
      concerns, appear as factors in the reluctance of physicians. Other reasons are
      lack of familiarity with issues relating to childhood, and the feeling of
      encroaching on a private and intimate sphere. The representations of physicians
      with regard to parenthood, parent-child relations, and the needs and difficulties
      of children, are often not integrated into the corpus of knowledge. These issues
      are more often aspects of physicians' own experience. CONCLUSION: The conflict of
      values and the uneasiness of the physicians suggest the need for ethical
      reflection groups or Balint groups.

PMID- 19854124
TI  - The CST complex and telomere maintenance: the exception becomes the rule.
AB  - Telomeres are bound and stabilized by two complexes-CST and shelterin-thought to
      be species specific and virtually unrelated. In this issue of Molecular Cell,
      Miyake et al. (2009) and Surovtseva et al. (2009) provide evidence that these
      complexes coexist and function at telomeres in many species.

PMID- 19854125
TI  - 22G-RNAs in transposon silencing and centromere function.
AB  - Three recent papers (Gu et al., 2009; Claycomb et al., 2009; van Wolfswinkel et
      al., 2009) provide evidence that links a new class of small RNAs and Argonaute
      associated complexes to centromere function and genome surveillance.

PMID- 19854126
TI  - Hormonal regulation of microRNA biogenesis.
AB  - In this issue of Molecular Cell, Yamagata et al. (2009) provide insight into the
      complex posttranscriptional regulation of miRNA biogenesis by showing that the
      processing of a subset of miRNAs is inhibited by the estrogen receptor.

PMID- 19854127
TI  - hMOF, a KAT(8) with many lives.
AB  - Dynamic lysine acetylation regulates proteins involved in diverse cellular
      processes, with individual enzymes often acetylating multiple substrates. Here,
      Li et al. (2009) show that the substrate specificity of hMOF/MYST1/KAT8 is
      controlled by differential interaction with two mutually exclusive partners.

PMID- 19854128
TI  - Targeting HSP70 for cancer therapy.
AB  - In a recent issue of Molecular Cell, Leu et al. (2009) demonstrate that a
      chemical inhibitor of HSP70 exerts prominent tumor-selective cytotoxic effects,
      thereby lending further support to the notion that non-oncogene addiction
      constitutes a promising target for anticancer therapy.

PMID- 19854129
TI  - "Cotranscriptionality": the transcription elongation complex as a nexus for
      nuclear transactions.
AB  - Much of the complex process of RNP biogenesis takes place at the gene
      cotranscriptionally. The target for RNA binding and processing factors is,
      therefore, not a solitary RNA molecule but, rather, a transcription elongation
      complex (TEC) comprising the growing nascent RNA and RNA polymerase traversing a
      chromatin template with associated passenger proteins. RNA maturation factors are
      not the only nuclear machines whose work is organized cotranscriptionally around
      the TEC scaffold. Additionally, DNA repair, covalent chromatin modification,
      "gene gating" at the nuclear pore, Ig gene hypermutation, and sister chromosome
      cohesion have all been demonstrated or suggested to involve a cotranscriptional
      component. From this perspective, TECs can be viewed as potent "community
      organizers" within the nucleus.

PMID- 19854130
TI  - RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and
      protects telomeres independently of the Pot1 pathway.
AB  - Budding yeast Cdc13, Stn1, and Ten1 form the CST complex to protect telomeres
      from lethal DNA degradation. It remains unknown whether similar complexes are
      conserved in higher eukaryotes or not. Here we isolated mammalian STN1 and TEN1
      homologs and CTC1 (conserved telomere maintenance component 1). The three
      proteins contain putative OB-fold domains and form a complex called CST, which
      binds to single-stranded DNA with high affinity in a sequence-independent manner.
      CST associates with a fraction of telomeres consistently during the cell cycle,
      in quiescent cells and Pot1-knockdown cells. It does not colocalize with
      replication foci in S phase. Significant increases in the abundance of single
      stranded G-strand telomeric DNA were observed in Stn1-knockdown cells. We propose
      that CST is a replication protein A (RPA)-like complex that is not directly
      involved in conventional DNA replication at forks but plays a role in DNA
      metabolism frequently required by telomeres.

PMID- 19854131
TI  - Conserved telomere maintenance component 1 interacts with STN1 and maintains
      chromosome ends in higher eukaryotes.
AB  - Orthologs of the yeast telomere protein Stn1 are present in plants, but other
      components of the Cdc13/Stn1/Ten1 (CST) complex have only been found in fungi.
      Here we report the identification of conserved telomere maintenance component 1
      (CTC1) in plants and vertebrates. CTC1 encodes an approximately 140 kDa telomere
      associated protein predicted to contain multiple OB-fold domains. Arabidopsis
      mutants null for CTC1 display a severe telomere deprotection phenotype
      accompanied by a rapid onset of developmental defects and sterility. Telomeric
      and subtelomeric tracts are dramatically eroded, and chromosome ends exhibit
      increased G overhangs, recombination, and end-to-end fusions. AtCTC1 both
      physically and genetically interacts with AtSTN1. Depletion of human CTC1 by RNAi
      triggers a DNA damage response, chromatin bridges, increased G overhangs, and
      sporadic telomere loss. These data indicate that CTC1 participates in telomere
      maintenance in diverse species and that a CST-like complex is required for
      telomere integrity in multicellular organisms.

PMID- 19854132
TI  - Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated
      induction of DNMT3B expression.
AB  - The RASSF1A tumor suppressor gene is epigenetically silenced in a variety of
      cancers. Here, we perform a genome-wide human shRNA screen and find that
      epigenetic silencing of RASSF1A requires the homeobox protein HOXB3. We show that
      HOXB3 binds to the DNA methyltransferase DNMT3B gene and increases its
      expression. DNMT3B, in turn, is recruited to the RASSF1A promoter, resulting in
      hypermethylation and silencing of RASSF1A expression. DNMT3B recruitment is
      facilitated through interactions with Polycomb repressor complex 2 and MYC, which
      is bound to the RASSF1A promoter. Mouse xenograft experiments indicate that the
      oncogenic activity of HOXB3 is due, at least in part, to epigenetic silencing of
      RASSF1A. Expression analysis in human lung adenocarcinoma samples reveals that
      RASSF1A silencing strongly correlates with overexpression of HOXB3 and DNMT3B.
      Analysis of human cancer cell lines indicates that the RASSF1A epigenetic
      silencing mechanism described here may be common in diverse cancer types.

PMID- 19854133
TI  - Biased chromatin signatures around polyadenylation sites and exons.
AB  - Core RNA-processing reactions in eukaryotic cells occur cotranscriptionally in a
      chromatin context, but the relationship between chromatin structure and pre-mRNA
      processing is poorly understood. We observed strong nucleosome depletion around
      human polyadenylation sites (PAS) and nucleosome enrichment just downstream of
      PAS. In genes with multiple alternative PAS, higher downstream nucleosome
      affinity was associated with higher PAS usage, independently of known PAS motifs
      that function at the RNA level. Conversely, exons were associated with distinct
      peaks in nucleosome density. Exons flanked by long introns or weak splice sites
      exhibited stronger nucleosome enrichment, and incorporation of nucleosome density
      data improved splicing simulation accuracy. Certain histone modifications,
      including H3K36me3 and H3K27me2, were specifically enriched on exons, suggesting
      active marking of exon locations at the chromatin level. Together, these findings
      provide evidence for extensive functional connections between chromatin structure
      and RNA processing.

PMID- 19854134
TI  - The Ess1 prolyl isomerase is required for transcription termination of small
      noncoding RNAs via the Nrd1 pathway.
AB  - Genome-wide studies have identified abundant small, noncoding RNAs, including
      small nuclear RNAs, small nucleolar RNAs (snoRNAs), cryptic unstable transcripts
      (CUTs), and upstream regulatory RNAs (uRNAs), that are transcribed by RNA
      polymerase II (pol II) and terminated by an Nrd1-dependent pathway. Here, we show
      that the prolyl isomerase Ess1 is required for Nrd1-dependent termination of
      noncoding RNAs. Ess1 binds the carboxy-terminal domain (CTD) of pol II and is
      thought to regulate transcription by conformational isomerization of Ser-Pro
      bonds within the CTD. In ess1 mutants, expression of approximately 10% of the
      genome was altered, due primarily to defects in termination of snoRNAs, CUTs,
      stable unannotated transcripts, and uRNAs. Ess1 promoted dephosphorylation of
      Ser5 (but not Ser2) within the CTD, most likely by the Ssu72 phosphatase. We also
      provide evidence for a competition between Nrd1 and Pcf11 for CTD binding that is
      regulated by Ess1. These data indicate that a prolyl isomerase is required for
      specifying the "CTD code."

PMID- 19854135
TI  - FLASH, a proapoptotic protein involved in activation of caspase-8, is essential
      for 3' end processing of histone pre-mRNAs.
AB  - 3' end processing of histone pre-mRNA requires U7 snRNP, which binds downstream
      of the cleavage site and recruits the endonuclease CPSF-73. U7 snRNP contains a
      unique Sm ring in which the canonical SmD2 protein is replaced by Lsm11. We used
      the yeast two-hybrid system to identify binding partners of Lsm11 and selected
      the proapoptotic protein FLASH. Human FLASH interacts with Lsm11 in vitro and
      stimulates 3' end processing of histone pre-mRNA in mammalian nuclear extracts.
      We also identified the FLASH ortholog in Drosophila and demonstrate that it
      interacts with Lsm11 in vitro and in vivo. Drosophila FLASH localizes to histone
      locus bodies, and its depletion from fly cells inhibits U7-dependent processing,
      resulting in polyadenylation of histone mRNAs. These results demonstrate that
      FLASH is an essential factor required for 3' end maturation of histone mRNAs in
      both vertebrates and invertebrates and suggest a potential link between this
      process and apoptosis.

PMID- 19854136
TI  - HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and
      splice factor 9G8.
AB  - A genetic screen previously identified the N-terminal 91 amino acids of the
      eukaryotic initiation factor 3 subunit f (N91-eIF3f) as a potent inhibitor of HIV
      1 replication. Overexpression of N91-eIF3f or full-length eIF3f reduced the level
      of HIV-1 mRNAs in the infected cell. Here we show that N91-eIF3f and eIF3f act by
      specifically blocking the 3' end processing of the HIV-1 pre-mRNA both in vivo
      and in vitro. Furthermore, the results suggest that eIF3f mediates this
      restriction of HIV-1 expression through the previously unsuspected involvement of
      a set of factors that includes eIF3f, the SR protein 9G8, and the cyclin
      dependent kinase 11 (CDK11). eIF3f affects HIV-1 3' end processing by modulating
      the sequence-specific recognition of the HIV-1 pre-mRNA by 9G8.

PMID- 19854137
TI  - Two mammalian MOF complexes regulate transcription activation by distinct
      mechanisms.
AB  - In mammals, MYST family histone acetyltransferase MOF plays important roles in
      transcription activation by acetylating histone H4 on K16, a prevalent mark
      associated with chromatin decondensation, and transcription factor p53 on K120,
      which is important for activation of proapoptotic genes. However, little is known
      about MOF regulation in higher eukaryotes. Here, we report that the
      acetyltransferase activity of MOF is tightly regulated in two different but
      evolutionarily conserved complexes, MSL and MOF-MSL1v1. Importantly, we
      demonstrate that while the two MOF complexes have indistinguishable activity on
      histone H4 K16, they differ dramatically in acetylating nonhistone substrate p53.
      We further demonstrate that MOF-MSL1v1 is specifically required for optimal
      transcription activation of p53 target genes both in vitro and in vivo. Our
      results support a model that these two MOF complexes regulate distinct stages of
      transcription activation in cooperation with other histone modifying activities.

PMID- 19854138
TI  - A ubiquitin replacement strategy in human cells reveals distinct mechanisms of
      IKK activation by TNFalpha and IL-1beta.
AB  - Lysine-63 (K63)-linked polyubiquitination has emerged as a mechanism regulating
      diverse cellular functions, including activation of the protein kinase IKK in the
      NF-kappaB pathways. However, genetic evidence for a key role of K63
      polyubiquitination in IKK activation is lacking. Here, we devise a tetracycline
      inducible RNAi strategy to replace endogenous ubiquitin with a K63R mutant in a
      human cell line. We demonstrate that K63 of ubiquitin and the catalytic activity
      of Ubc13, an E2 that catalyzes K63 polyubiquitination, are required for IKK
      activation by IL-1beta, but surprisingly, not by TNFalpha. We further show that
      IKK activation by TNFalpha requires Ubc5, which functions with the E3 cIAP1 to
      catalyze polyubiquitination of RIP1 not restricted to K63 of ubiquitin. These
      results indicate that distinct ubiquitin-dependent mechanisms are employed for
      IKK activation by different pathways. The ubiquitin replacement methodology
      described here provides a means to investigate the function of polyubiquitin
      topology in various cellular processes.

PMID- 19854139
TI  - Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3.
AB  - The mitochondrial antiviral signaling protein (MAVS; also known as IPS-1, VISA,
      and CARDIF) is essential for innate immune response against RNA viruses. MAVS
      transduces signals from the cytosolic RIG-I-like receptors, which bind to viral
      RNAs. But how MAVS activates downstream transcription factors such as IRF3 to
      induce type-I interferons is not well understood. We have established a cell-free
      system in which mitochondria derived from virus-infected cells activate IRF3 in
      the cytosol. Fractionation of the cytosol led to the identification of Ubc5 as a
      ubiquitin-conjugating enzyme (E2) required for IRF3 activation. Using an
      inducible RNAi strategy, we demonstrate that catalytically active Ubc5 is
      required for IRF3 activation by viral infection. The activation of IRF3 also
      requires two ubiquitin-binding domains of NEMO. Furthermore, we show that
      replacement of endogenous ubiquitin with its K63R mutant abolishes viral
      activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in
      IRF3 activation.

PMID- 19854140
TI  - Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes.
AB  - Inappropriate activation of oncogenic kinases at intracellular locations is
      frequently observed in human cancers, but its effects on global signaling are
      incompletely understood. Here, we show that the oncogenic mutant of Flt3 (Flt3
      ITD), when localized at the endoplasmic reticulum (ER), aberrantly activates
      STAT5 and upregulates its targets, Pim-1/2, but fails to activate PI3K and MAPK
      signaling. Conversely, membrane targeting of Flt3-ITD strongly activates the MAPK
      and PI3K pathways, with diminished phosphorylation of STAT5. Global
      phosphoproteomics quantified 12,186 phosphorylation sites, confirmed compartment
      dependent activation of these pathways and discovered many additional components
      of Flt3-ITD signaling. The differential activation of Akt and Pim kinases by ER
      retained Flt3-ITD helped to identify their putative targets. Surprisingly, we
      find spatial regulation of tyrosine phosphorylation patterns of the receptor
      itself. Thus, intracellular activation of RTKs by oncogenic mutations in the
      biosynthetic route may exploit cellular architecture to initiate aberrant
      signaling cascades, thus evading negative regulation.

PMID- 19854141
TI  - Maturation of microRNA is hormonally regulated by a nuclear receptor.
AB  - Steroid hormones and their cognate nuclear receptors exert a wide spectrum of
      biological actions through regulation of transcriptional and posttranscriptional
      processes. However, the underlying molecular mechanism by which steroid hormones
      control posttranscriptional processes is largely unknown. We now report that
      estrogen receptor alpha (ERalpha) inhibits the maturation of a particular
      microRNA (miRNA) and thereby stabilizes the mRNA of an ERalpha target gene
      through the 3'UTR. Estrogen-bound ERalpha downregulated expression of a set of
      miRNAs in both animals and cultured cells. Activated ERalpha attenuated the
      processing of primary miRNAs into pre-miRNAs through estrogen-dependent
      association with the Drosha complex, resulting in stabilization of the transcript
      of an ERalpha target gene through its 3'UTR. Thus, a steroid hormone achieves
      posttranscriptional control by regulating the maturation of miRNA.

PMID- 19854142
TI  - Laboratory and field evaluation of neem (Azadirachta indica A. Juss) and
      Chinaberry (Melia azedarach L.) oils as repellents against Phlebotomus orientalis
      and P. bergeroti (Diptera: Psychodidae) in Ethiopia.
AB  - The study evaluated the efficacy of neem (Azadirachta indica A. Juss.) and
      Chinaberry (Melia azedarach L.) seed oils as repellents against laboratory and
      field populations of some sandflies in Ethiopia. In the laboratory,
      concentrations of 2% and 5% neem oil in coconut oil tested against Phlebotomus
      orientalis (vector of visceral leishmaniasis) provided 96.28% (95% CI=95.60
      96.97) protection up to a mean time of 7h and 20 min and 98.26% (95% CI=93.46
      104. 07) protection up to 9h, respectively. Similarly, M. azedarach oil at 2%
      concentration produced 95.13% (95% CI=90.74-99.52) protection for the same
      duration (7h and 20 min), while the 5% oil gave 96.20 (95% CI=86.98-105.41)
      protection for 8h and 20 min against the same species with no significant
      difference in percentage protection between the two oils at 2% and 5%
      concentrations. In the field tests with only neem oil (A. indica) against field
      populations of P. orientalis and P. bergeroti, similar high level of repellencies
      were recorded with about the same duration of protection. Application of both
      neem and Chinaberry oils can be safe and low-cost means of personal protection
      against sandfly bites in endemic areas of Ethiopia, if the community is advised
      and encouraged to grow the plants abundantly.

PMID- 19854143
TI  - Knowledge, perceptions and practices of farming communities on linkages between
      malaria and agriculture in Mvomero District, Tanzania.
AB  - This study was carried out to determine knowledge, perceptions and practices of
      farming communities on linkages between agriculture and malaria in Mvomero
      District in Tanzania. A total of 661 adult males and females were interviewed
      using a structured questionnaire. Most respondents (85.6%) were engaged in crop
      production. Significantly, a larger proportion (55.2%) of the respondents had
      primary school education (P<0.001). Majority (88.2%) respondents described
      malaria as the most important public health problem. However, only 48.2% of the
      respondents had high knowledge of malaria. The level of knowledge on malaria was
      associated with level of education of the respondent. Those who had attended at
      least primary school education were more knowledgeable that those without formal
      education. A significantly larger proportion (67%) of the respondents experienced
      most malaria episodes during the rainy season (P<0.001). Respondents with low
      knowledge on malaria experienced 2.3 times more malaria cases in their households
      than those with higher knowledge. Respondents with low knowledge preferred to
      seek care from health facilities (OR: 7.28) than those with high knowledge (OR:
      0.15). Rice farming was significantly associated with malaria transmission
      compared to either maize or sugarcane farming (P<0.001). Cattle, sheep and goats
      were the domestic animals most frequently incriminated to create aquatic habitats
      for mosquito breeding. Householders with formal education (OR: 4.6, CI: 1.33
      15.89, P-value=0.016) and higher knowledge (OR: 1.7, CI: 1.15-2.55, P
      value=0.008) reported to incur large losses when having a malaria case than those
      without education/low knowledge. Majority (60.2%) of the respondent owned at
      least an insecticide treated mosquito net (ITN). Respondents with higher
      knowledge of malaria were likely to own at least an ITN than those with low
      knowledge (P<0.001). In conclusion, the knowledge on malaria and its linkage with
      agriculture among farming communities in Mvomero District is low. Malaria is a
      complex health problem and its control approach needs understanding of the
      environmental factors associated with agricultural practices. It therefore is
      important that education and communication messages on malaria targeting farming
      communities take into consideration local agricultural practices.

PMID- 19854144
TI  - Amplified fragment length polymorphism (AFLP) analysis is useful for
      distinguishing Leishmania species of visceral and cutaneous forms.
AB  - The Leishmania strains belonging to cutaneous leishmaniasis (CL) and visceral
      leishmaniasis (VL) have been reported to possess close homology in genome
      profiles. To confirm this on genetic basis an attempt was made to differentiate
      Leishmania major; Leishmania tropica and Leishmania donovani genetically for the
      first time using amplified fragment length polymorphism (AFLP)--a high throughput
      DNA fingerprinting technique. The objective of this research work was to identify
      DNA markers of CL and VL. Ten combinations of selective primers detect a total of
      1487 informative AFLP marker. Percentage of polymorphism was 45.12%. Three
      hundred and thirty-seven unique AFLP markers were also identified in three
      species of Leishmania. A clear distinction was revealed between L. major and L.
      donovani. It was inferred by AFLP analysis that a higher rate of polymorphisms
      occurred among Leishmania species which indicate the distinguished pattern of the
      disease cause by Leishmania, i.e. VL and CL. Analysis based on polymorphic AFLP
      markers revealed considerably high genetic variation among the genome of these
      species which was sufficient to distinguish between CL and VL.

PMID- 19854145
TI  - Benznidazole alters the pattern of Cyclophosphamide-induced reactivation in
      experimental Trypanosoma cruzi-dependent lineage infection.
AB  - The factors involved in the reactivation of chronic Chagas disease infection are
      not clear enough and may be related to host immune unbalance and/or parasite
      genetic diversity. To evaluate the role of the Trypanosoma cruzi genetic
      background in the Chagas disease reactivation, we inoculated Cyclophosphamide
      immunosupressed (CyI) Swiss mice with clonal stocks from T. cruzi I (Cuica cl1,
      P209 cl1, Gamba cl1, SP104 cl1), T. cruzi II (IVV cl4, MVB cl8) and T. cruzi
      (Bug2148 cl1, MN cl2) lineages. We used the parasitemia as the parameter for
      Chagas disease reactivation and observed that CyI animals infected with T. cruzi
      stocks showed no reactivation and those infected with T. cruzi II stocks showed
      only 5% of reactivation. In contrast, immunosuppressed mice infected with stocks
      from T. cruzi I lineage showed 77.5 and 51.25% reactivation of the infection when
      Cyclophosphamide treatment was performed 60 and 180 days after inoculation,
      respectively. Next, we evaluated the efficacy of the Benznidazole (Bz) pre
      treatment in reducing or preventing the recurrence of the infection in these CyI
      animals. In general, the percentage of the parasite recurrence was not altered
      among the CyI mice that received the Bz pre-treatment during the acute phase of
      the infection. Interestingly, when pre-Bz treatment was performed during the
      chronic phase, we observed two different patterns of response: (i) an increased
      protection among the animals inoculated with the SP104 cl1 (genotype 19) and
      Cuica cl1 (genotype 20) stocks; (ii) an increased percentage of parasitemia
      reactivation among mice inoculated with Gamba cl1 (genotype 19) and P209 cl1
      (genotype 20) T. cruzi stocks. Our results corroborate our hypothesis by showing
      that the T. cruzi genetic background in combination with specific Bz treatment
      has an important role in the Chagas disease reactivation in immunosuppressed
      animals.

PMID- 19854146
TI  - A spectrophotometric method for the determination of zinc, copper, and cobalt
      ions in metalloproteins using Zincon.
AB  - Zincon (2-carboxy-2'-hydroxy-5'-sulfoformazylbenzene) has long been known as an
      excellent colorimetric reagent for the detection of zinc and copper ions in
      aqueous solution. To extend the chelator's versatility to the quantification of
      metal ions in metalloproteins, the spectral properties of Zincon and its
      complexes with Zn(2+), Cu(2+), and Co(2+) were investigated in the presence of
      guanidine hydrochloride and urea, two common denaturants used to labilize metal
      ions in proteins. These studies revealed the detection of metals to be generally
      more sensitive with urea. In addition, pH profiles recorded for these metals
      indicated the optimal pH for complex formation and stability to be 9.0. As a
      consequence, an optimized method that allows the facile determination of Zn(2+),
      Cu(2+), and Co(2+) with detection limits in the high nanomolar range is
      presented. Furthermore, a simple two-step procedure for the quantification of
      both Zn(2+) and Cu(2+) within the same sample is described. Using the
      prototypical Cu(2+)/Zn(2+)-protein superoxide dismutase as an example, the
      effectiveness of this method of dual metal quantification in metalloproteins is
      demonstrated. Thus, the spectrophotometric determination of metal ions with
      Zincon can be exploited as a rapid and inexpensive means of assessing the metal
      contents of zinc-, copper-, cobalt-, and zinc/copper-containing proteins.

PMID- 19854147
TI  - Time-dependent density functional theory-assisted absolute configuration
      determination of cis-dihydrodiol metabolite produced from isoflavone by biphenyl
      dioxygenase.
AB  - Escherichia coli cells containing the biphenyl dioxygenase genes bphA1A2A3A4 from
      Pseudomonas pseudoalcaligenes KF707 were found to biotransform isoflavone and
      produced a metabolite that was not found in a control experiment. Liquid
      chromatography/mass spectrometry (LC/MS) and (1)H and (13)C nuclear magnetic
      resonance (NMR) analyses indicated that biphenyl dioxygenase induced 2',3'-cis
      dihydroxylation of the B-ring of isoflavone. In a previous report, the same
      enzyme showed dioxygenase activity toward flavone, producing flavone 2',3'-cis
      dihydrodiol. Due to growing interest in flavone chemistry and the absolute
      configuration of natural products, time-dependent density functional theory (TD
      DFT) calculations were combined with circular dichroism (CD) spectroscopy to
      determine the absolute configuration of the isoflavone dihydrodiol. By
      computational methods, the structure of the isoflavone metabolite was determined
      to be 3-[(5S,6R)-5,6-dihydroxycyclohexa-1,3-dienyl]-4H-chromen-4-one. This
      structure was confirmed further by the modified Mosher's method. The same
      protocol was applied to the flavone metabolite, and the absolute configuration
      was determined to be 2-[(5S,6R)-5,6-dihydroxycyclohexa-1,3-dienyl]-4H-chromen-4
      one. After determination of the absolute configurations of the biotransformation
      products, we suggest the binding mode of these substrate analogs to the enzyme
      active site.

PMID- 19854148
TI  - A continuous assay for alpha-methylacyl-coenzyme A racemase using circular
      dichroism.
AB  - alpha-Methylacyl-coenzyme A racemase (AMACR) catalyzes the epimerization of (2R)-
      and (2S)-methyl branched fatty acyl-coenzyme A (CoA) thioesters. AMACR is a
      biomarker for prostate cancer and a putative target for the development of
      therapeutic agents directed against the disease. To facilitate development of
      AMACR inhibitors, a continuous circular dichroism (CD)-based assay has been
      developed. The open reading frame encoding AMACR from Mycobacterium tuberculosis
      (MCR) was subcloned into a pET15b vector, and the enzyme was overexpressed and
      purified using metal ion affinity chromatography. The rates of MCR-catalyzed
      epimerization of either (2R)- or (2S)-ibuprofenoyl-CoA were determined by
      following the change in ellipticity at 279nm in the presence of octyl-beta-d
      glucopyranoside (0.2%). MCR exhibited slightly higher affinity for (2R)
      ibuprofenoyl-CoA (K(m)=48+/-5microM, k(cat)=291+/-30s(-1)), but turned over (2S)
      ibuprofenoyl-CoA (K(m)=86+/-6microM, k(cat)=450+/-14s(-1)) slightly faster. MCR
      expressed as a fusion protein bearing an N-terminal His(6)-tag had a catalytic
      efficiency (k(cat)/K(m)) that was reduced 22% and 47% in the 2S-->2R and 2R-->2S
      directions, respectively, relative to untagged enzyme. The continuous CD-based
      assay offers an economical and efficient alternative method to the labor
      intensive, fixed-time assays currently used to measure AMACR activity.

PMID- 19854149
TI  - Comparative determination of some phytohormones in wild-type and genetically
      modified plants by gas chromatography-mass spectrometry and high-performance
      liquid chromatography-tandem mass spectrometry.
AB  - The analytical performances of two optimized analytical methodologies used for
      the determination of auxins, cytokinins, and abscisic acid in plant samples were
      critically compared. Phytohormones were extracted from Nicotiana glauca samples
      using a modified Bieleski solvent and determined both by gas chromatography-mass
      spectrometry (GC-MS), after derivatization with N,O
      bis(trimethylsilyl)trifluoroacetamide (BSTFA), and by high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) on the Bieleski extract
      without any further treatment. HPLC-MS/MS gave better results in terms of higher
      coefficients of determination of the calibration curves, higher and more
      reproducible recoveries, lower limits of detection, faster sample preparation,
      and higher sample throughput. Thus, two sets of N. glauca and N. langsdorffii
      samples, both wild-type and genetically modified by inserting the glucocorticoid
      receptor (GR) gene encoding for the rat glucocorticoid receptor, were first
      characterized by reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis and then analyzed by HPLC-MS/MS. Significant differences in the
      phytohormone content between the two sample sets were found and are very
      important in terms of understanding the mechanisms and effects on growth
      processes and the development of transgenic plants.

PMID- 19854150
TI  - A robust assay measuring GLUT4 translocation in rat myoblasts overexpressing
      GLUT4-myc and AS160_v2.
AB  - Muscle and fat cells translocate GLUT4 (glucose transporter 4) to the plasma
      membrane when stimulated by insulin. Usually, this event is measured in
      differentiated adipocytes, myotubes, or cell lines overexpressing tagged GLUT4 by
      immunostaining. However, measurement of the translocation in differentiated
      adipocytes or myotubes or GLUT4 overexpressing cell lines is difficult because of
      high assay variability caused by either the differentiation protocol or low assay
      sensitivity. We recently reported the identification of a novel splice variant of
      AS160 (substrate of 160kDa), namely AS160_v2, and showed that its coexpression
      with GLUT4 in L6 myoblasts increased the insulin-stimulated glucose uptake rate
      due to an increased amount of GLUT4 on the cell surface. L6 cells, which
      coexpress myc-tagged GLUT4 and AS160_v2, can be efficiently used to generate an
      assay useful for identifying compounds that affect cellular responses to insulin.
      We compared the EC(50) values for radioactive glucose uptake and GLUT4
      translocation of different insulins and several small molecules to validate the
      assay. The use of L6 cells overexpressing AS160_v2 can be considered as a novel
      tool for the characterization of molecules modulating insulin signaling and GLUT4
      translocation, and an image-based assay increases our confidence in the mode of
      action of the compounds identified.

PMID- 19854151
TI  - Mammalian Oxa1 protein is useful for assessment of submitochondrial protein
      localization and mitochondrial membrane integrity.
AB  - Taking advantage of the unique topology of oxidase assembly 1 (Oxa1) protein, a
      mitochondrial inner membrane protein with N (intermembrane space)-C (matrix)
      orientation, we explored the usefulness of the protein as a marker for
      submitochondrial protein localization. Mammalian Oxa1 protein exhibited different
      proteolytic patterns depending on mitochondrial membrane integrity, and in
      mitochondria with a disrupted outer membrane and outer and inner membranes, the
      proteolytic patterns of Oxa1 protein were consistent with those of mitochondrial
      intermembrane space and matrix marker proteins, respectively, suggesting that
      Oxa1 protein, a single molecule, can serve as a versatile submitochondrial
      localization marker that doubles as a membrane integrity marker.

PMID- 19854152
TI  - Peroxisomal localization and function of NADP+ -specific isocitrate
      dehydrogenases in yeast.
AB  - Yeast peroxisomal NADP(+)-specific isocitrate dehydrogenase (IDP3) contains a
      canonical type I peroxisomal targeting sequence (a carboxyl-terminal Cys-Lys-Leu
      tripeptide), and provides the NADPH required for beta-oxidation of some fatty
      acids in that organelle. Cytosolic yeast IDP2 carrying a PTS1 (IDP2(+CKL)) was
      only partially localized to peroxisomes, and the enzyme was able to function in
      lieu of either peroxisomal IDP3 or cytosolic IDP2. The analogous isocitrate
      dehydrogenase enzyme (IDPA) from Aspergillus nidulans, irrespective of the
      presence or absence of a putative PTS1, was found to exhibit patterns of dual
      compartmental distribution and of dual function in yeast similar to those
      observed for IDP2(+CKL). To test a potential cellular limit on peroxisomal
      levels, authentic yeast IDP3, which is normally strictly peroxisomal, was over
      expressed. This also resulted in dual distribution and function of the enzyme in
      both the cytosol and in peroxisomes, supporting the possibility of a restriction
      on organellar amounts of IDP.

PMID- 19854153
TI  - Incorporation of the chlorophyll d-binding light-harvesting protein from
      Acaryochloris marina and its localization within the photosynthetic apparatus of
      Synechocystis sp. PCC6803.
AB  - The gene encoding a chlorophyll d-binding light-harvesting protein, pcbA from
      Acaryochloris marina (now called as accessory Chlorophyll Binding Protein CBPII)
      marked with a His-tag was transformed into the genome of Synechocystis PCC6803.
      Protein gel electrophoresis and western blotting confirmed that this foreign
      chlorophyll d-binding protein CBPII was expressed and integrated into the
      thylakoid membrane and bound with chlorophyll a, the only type of chlorophyll
      present in Synechocystis PCC 6803. Native electrophoresis suggested that CBPII
      interacts with photosystem II of Synechocystis PCC 6803. Surprisingly, spectral
      analyses showed that the phycobiliproteins were suppressed in the transformed
      Synechocystis pcbA(+), with a lower ratio of phycobilins to chlorophyll a. These
      results suggest that there are competitive interactions between the external
      antenna system of phycobiliproteins and the integral antenna system of
      chlorophyll-bound protein complexes.

PMID- 19854154
TI  - Knockdown of Cav2.1 calcium channels is sufficient to induce neurological
      disorders observed in natural occurring Cacna1a mutants in mice.
AB  - The CACNA1A gene encodes the poreforming, voltage-sensitive subunit of the
      voltage-dependent Ca(v)2.1 calcium channel. Mutations in this gene have been
      linked to several human disorders, including familial hemiplegic migraine type 1,
      episodic ataxia type 2, and spinocerebellar ataxia type 6. In mice, mutations of
      the homolog Cacna1a cause recessively inherited phenotypes in tottering, rolling
      Nagoya, rocker, and leaner mice. Here we describe two knockdown mice with 28.4+/
      3.4% and 13.8+/-3.3% of the wild-type Ca(v)2.1 quantity. 28.4+/-3.4% level
      mutants displayed ataxia, absence-like seizures and progressive cerebellar
      atrophy, although they had a normal life span. Mutants with 13.8+/-3.3% level
      exhibited ataxia severer than the 28.4+/-3.4% level mutants, absence-like
      seizures and additionally paroxysmal dyskinesia, and died premature around 3
      weeks of age. These results indicate that knock down of Ca(v)2.1 quantity to
      13.8+/-3.3% of the wild-type level are sufficient to induce the all neurological
      disorders observed in natural occurring Cacna1a mutants. These knockdown animals
      with Ca(v)2.1 calcium channels intact can contribute to functional studies of the
      molecule in the disease.

PMID- 19854155
TI  - Basic fibroblast growth factor promotes the generation of microtubule-associated
      protein 2-positive cells from microglia.
AB  - We recently demonstrated that microglia as multipotential stem cells give rise to
      microtubule-associated protein 2 (MAP2)-positive and glial fibrillary acidic
      protein (GFAP)-positive cells and that microglia-derived MAP2-positive cells
      possess properties of functional neurons. In this study, we investigated the role
      of fibroblast growth factor (FGF) signaling in the molecular mechanism underlying
      the generation of microglia-derived MAP2-positive and GFAP-positive cells. Real
      time quantitative PCR analyses demonstrated that mRNA levels of a family of three
      FGF receptors, Fgfr1-3, were upregulated in microglia treated with 70% fetal
      bovine serum (FBS). Immunocytochemical analyses demonstrated that basic FGF
      (bFGF) promoted the generation of microglia-derived MAP2-positive and GFAP
      positive cells, and the FGF receptor tyrosine kinase inhibitor SU5402 and the MEK
      inhibitor PD98059 both inhibited this process. Western blot analyses demonstrated
      that bFGF increased phosphorylated ERK1/2 levels without altering total ERK1/2
      levels. These results suggest that bFGF promotes the generation of microglia
      derived MAP2-positive and GFAP-positive cells via FGF receptors and the ERK-MAP
      kinase pathway.

PMID- 19854156
TI  - Simple strategy for bone regeneration with a BMP-2/7 gene expression cassette
      vector.
AB  - Bone morphogenetic protein (BMP) is one of the most promising candidates for bone
      regeneration therapy. Heterodimers of BMP family proteins, such as BMP-2/4 or BMP
      2/7, are well known to have stronger osteoinduction activity than BMP homodimers.
      Here, we constructed a double gene cassette vector encoding BMP-2 and BMP-7,
      pCAGGS-BMP-2/7, and examined its potential for osteoinduction in vitro and in
      vivo. Expression of the pCAGGS-BMP-2/7 vector induced osteogenic differentiation
      in various cell lines with the same efficiency as BMP-2 and BMP-7 co-expressed
      from separate vectors. Moreover, the pCAGGS-BMP-2/7 vector strongly induced bone
      formation in rat skeletal muscle when introduced by in vivo electroporation,
      compared with BMP-2 or BMP-7 alone. Thus, our BMP-2/7 double gene cassette
      vector, or some variation of it, may be applicable for the future clinical
      induction of bone formation, because it does not require multiple vectors or
      complicated preparation.

PMID- 19854158
TI  - Prohibitin interacts with phosphatidylinositol 3,4,5-triphosphate (PIP3) and
      modulates insulin signaling.
AB  - Mitochondrial protein prohibitin (PHB) is known to associate with the plasma
      membrane of various cell types. However, biological function of plasma membrane
      associated PHB is not known. Recently we have shown that PHB undergoes tyrosine
      phosphorylation in response to insulin and here we report that PHB interacts with
      phosphatidylinositol 3,4,5-triphosphate (PIP3). Furthermore, we demonstrate that
      over expression of PHB attenuates insulin signaling downstream of
      phosphatidylinositol 3 (PI3) kinase. This effect was not observed with over
      expression of tyrosine phosphorylation site mutant-PHB suggesting a role for
      tyrosine phosphorylation of PHB in this process. Interestingly phosphorylation of
      PHB by Akt attenuates its interaction with PIP3 and enhances insulin signaling.
      Thus, phosphorylation of PHB and its interaction with PIP3 may be a part of the
      regulatory mechanisms that is involved in the modulation of insulin signaling. We
      speculate that phosphorylation of PHB may serve as a general mechanism in the
      regulation of PI3 kinase signaling including growth factors and immune receptor
      signaling.

PMID- 19854157
TI  - Tumor suppressor CADM1 is involved in epithelial cell structure.
AB  - The tumor suppressor, CADM1, is involved in cell adhesion and preferentially
      inactivated in invasive cancer. We have previously reported that CADM1 associates
      with an actin-binding protein, 4.1B/DAL-1, and a scaffold protein, membrane
      protein palmitoylated 3 (MPP3)/DLG3. However, underlying mechanism of tumor
      suppression by CADM1 is not clarified yet. Here, we demonstrate that MPP1/p55 and
      MPP2/DLG2, as well as MPP3, interact with both CADM1 and 4.1B, forming a
      tripartite complex. We then examined cell biological roles of CADM1 and its
      complex in epithelia using HEK293 cells. Among MPP1-3, MPP2 is recruited to the
      CADM1-4.1B complex in the early process of adhesion in HEK293 cells. By
      suppression of CADM1 expression using siRNA, HEK293 lose epithelia-like structure
      and show flat morphology with immature cell adhesion. 4.1B and MPP2, as well as E
      cadherin and ZO-1, are mislocalized from the membrane by depletion of CADM1 in
      HEK293. Mislocalization of MPP2 is also observed in several cancer cells lacking
      CADM1 expression with the transformed morphology. These findings suggest that
      CADM1 is involved in the formation of epithelia-like cell structure with 4.1B and
      MPP2, while loss of its function could cause morphological transformation of
      cancer cells.

PMID- 19854159
TI  - 3,3'-Diindolylmethane attenuates experimental arthritis and osteoclastogenesis.
AB  - 3,3'-Diindolylmethane (DIM) is a natural compound formed during the autolysis of
      glucobrassicin present in Brassica food plants. This study aimed to investigate
      the therapeutic efficacies of DIM on experimental arthritis. The effects of DIM
      on experimental arthritis were examined on a rat model of adjuvant-induced
      arthritis (AIA), with daily AIA paw swelling observation and
      histological/radiographic analysis. To elucidate the possible mechanisms of its
      action, serum cytokine levels as well as the expression of receptor activator for
      nuclear factor kappa B ligand (RANKL) in infected tissues were subsequently
      analyzed. The impact of DIM on osteoclastogenesis was further investigated on a
      mouse model of endotoxin-induced bone resorption (EIBR) and in vitro cultures of
      fibroblast-like cells and osteoblasts, with RANKL expression being evaluated with
      great interest. The administration of DIM was demonstrated to attenuate AIA in
      animal models, as judged by clinical and histologic indices of inflammation and
      tissue damage. On the one hand, DIM could reduce the expression of several
      inflammatory cytokines, which was, however, not adequate to prevent the
      development of the arthritis. On the other hand, DIM was shown to effectively
      inhibit the expression of RANKL, leading to the blockade of osteoclastogenesis
      and consequently an alleviation of experimental arthritis. Further in vitro and
      in vivo studies confirmed the inhibition of RANKL by DIM. DIM has shown anti
      arthritis activity in animal models via inhibiting the expression of RANKL, and
      thus may offer potential treatments for arthritis and associated disorders.

PMID- 19854160
TI  - Inhibition of hepatic carnitine palmitoyl-transferase I (CPT IA) by valproyl-CoA
      as a possible mechanism of valproate-induced steatosis.
AB  - BACKGROUND/AIMS: Carnitine palmitoyl-transferase I (CPT I) catalyses the
      synthesis of long-chain (LC)-acylcarnitines from LC-acyl-CoA esters. It is the
      rate-limiting enzyme of mitochondrial fatty acid beta-oxidation (FAO) pathway and
      its activity is regulated by malonyl-CoA. The antiepileptic drug valproic acid
      (VPA) is a branched chain fatty acid that is activated to the respective CoA
      ester in the intra- and extra-mitochondrial compartments. This drug has been
      associated with a clear inhibition of mitochondrial FAO, which motivated our
      study on its potential effect on hepatic CPT I. METHODS: To investigate the
      effect of valproyl-CoA (VP-CoA) on CPT I, we performed in vitro studies using
      control human fibroblasts and rat CPT IA expressed in Saccharomyces cerevisiae.
      In addition to the wild-type enzyme, two mutant rCPT IAs were studied, one of
      which showing increased sensitivity towards malonyl-CoA (S24A/Q30A), whereas the
      other one is insensitive to malonyl-CoA (E3A). RESULTS: We demonstrate that VP
      CoA inhibits the CPT I activity in control fibroblasts. Similar results were
      obtained using rCPT IA WT and S24A/Q30A. Importantly, VP-CoA also inhibited the
      activity of the rCPT IA E3A. We show that VP-CoA inhibits CPT IA competitively
      with respect to palmitoyl-CoA, and non-competitively to carnitine. Evidence is
      provided that VP-CoA interferes at the catalytic domain of CPT IA affecting the
      sensitivity for malonyl-CoA. CONCLUSIONS: The interference of VP-CoA with CPT IA,
      a pivotal enzyme in mitochondrial fatty acid beta-oxidation, may be a crucial
      mechanism in the drug-induced hepatotoxicity and the weight gain frequently
      observed in patients under VPA therapy.

PMID- 19854161
TI  - Transcriptional and post-transcriptional regulation of iNOS expression in human
      chondrocytes.
AB  - Chondrocytes are important for the development and maintenance of articular
      cartilage. However, both in osteoarthritis (OA) and rheumatoid arthritis (RA)
      chondrocytes are involved in the process of cartilage degradation and synthesize
      important immunomodulatory mediators, including nitric oxide (NO) generated by
      the inducible NO synthase (iNOS). To uncover the role of iNOS in the
      pathomechanisms of OA and RA, we analyzed the regulation of iNOS expression using
      immortalized human chondrocytes as a reproducible model. In C-28/I2 chondrocytes,
      iNOS expression was associated with the expression of the chondrocyte phenotype.
      Peak induction by a cytokine cocktail occurred between 6 and 8h and declined by
      24h. Inhibition of p38MAPK, NF-kappaB and the JAK2-STAT-1alpha pathways resulted
      in a reduction of iNOS expression. In contrast to other cell types, the cytokine
      mediated induction of the human iNOS promoter paralleled the induction rate of
      the iNOS mRNA expression in C-28/I2 chondrocytes. However, in addition post
      transcriptional regulation of iNOS expression by the RNA binding protein KSRP
      seems to operate in these cells. As seen in other chondrocyte models,
      glucocorticoids were not able to inhibit cytokine-induced iNOS expression in C
      28/I2 cells, due to the lack of the glucocorticoid receptor mRNA expression. In
      this model of glucocorticoid-resistance, the new fungal anti-inflammatory
      compound S-curvularin was able to inhibit cytokine-induced iNOS expression and
      iNOS-dependent NO-production. In summary, we demonstrate for the first time that
      differentiated human immortalized C-28/I2 chondrocytes are a representative cell
      culture model to investigate iNOS gene expression in human joint diseases.

PMID- 19854162
TI  - Hippocampal infusions of MARCKS peptides impair memory of rats on the radial-arm
      maze.
AB  - In vitro hippocampal studies by Gay et al. (2008) demonstrated that a
      myristoylated alanine-rich C kinase substrate (MARCKS) peptide comprising the
      phosphorylation site or effector domain of the protein acts as a powerful
      inhibitor of alpha7 nicotinic acetylcholine receptors (nAChRs), which are known
      to be critically involved in memory function. However, behavioral consequences of
      hippocampal MARCKS peptide infusions have not been investigated. The purpose of
      the current study was to determine if local infusions in the rat ventral
      hippocampus of long (comprising amino acids 151-175) and short (amino acids 159
      165) forms of MARCKS peptides could affect memory performance in the 16-arm
      radial maze. Our results demonstrated a dramatic impairment of both working
      (changing) and reference (constant) memory with MARCKS(151-175) only. The shorter
      MARCKS peptide did not affect memory performance. This is in line with in vitro
      results reported by Gay et al. (2008) that long, but not short, MARCKS peptides
      inhibit alpha7 nAChRs. We also found that the effect of the MARCKS(151-175)
      peptide was dose-dependent, with a robust memory impairment at 10 microg/side,
      and smaller inconsistent effects at lower doses. Our present behavioral study,
      together with the earlier in vitro study by Gay et al. (2008), suggests that
      effector domain MARCKS peptides could play a significant role in memory
      regulation and impairment.

PMID- 19854163
TI  - The electrophysiological correlate of saliency: evidence from a figure-detection
      task.
AB  - Although figure-ground segregation in a natural environment usually relies on
      multiple cues, we experience a coherent figure without usually noticing the
      individual single cues. It is still unclear how various cues interact to achieve
      this unified percept and whether this interaction depends on task demands.
      Studies investigating the effect of cue combination on the human EEG are still
      lacking. In the present study, we combined psychophysics, ERP and time-frequency
      analysis to investigate the interaction of orientation and spatial frequency as
      visual cues in a figure detection task. The figure was embedded in a matrix of
      Gabor elements, and we systematically varied figure saliency by changing the
      underlying cue configuration. We found a strong correlation between the posterior
      P2 amplitude and the perceived saliency of the figure: the P2 amplitude decreased
      with increasing saliency. Analogously, the power of the theta-band decreased for
      more salient figures. At longer latencies, the posterior P3 component was
      modulated in amplitude and latency, possibly reflecting increased decision
      confidence at higher saliencies. In conclusion, when the cue composition (e.g.
      one or two cues) or cue strength is changed in a figure detection task, first
      differences in the electrophysiological response reflect the perceived saliency
      and not directly the underlying cue configuration.

PMID- 19854165
TI  - Glanzmann thrombasthenia: an update.
AB  - Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder
      characterized by qualitative or quantitative abnormalities of the platelet
      membrane glycoprotein (GP) IIb/IIIa. Physiologically, this platelet receptor
      normally binds several adhesive plasma proteins, and this facilitates attachment
      and aggregation of platelets to ensure thrombus formation at sites of vascular
      injury. The lack of resultant platelet aggregation in GT leads to mucocutaneous
      bleeding whose manifestation may be clinically variable, ranging from easy
      bruising to severe and potentially life-threatening hemorrhages. In this review
      we discuss the main characteristics of GT, focusing on molecular defects,
      diagnostic evaluation and treatment strategies.

PMID- 19854164
TI  - A quantitative study of brainstem projections from lamina I neurons in the
      cervical and lumbar enlargement of the rat.
AB  - Lamina I of the rat spinal cord contains neurons that project to various brain
      areas including thalamus, periaqueductal grey matter (PAG), lateral parabrachial
      area (LPb), caudal ventrolateral medulla and a region in dorsal medulla that
      includes the nucleus tractus solitarius and dorsal reticular nucleus. We have
      shown that spinothalamic lamina I neurons are infrequent in rat lumbar
      enlargement, where they constitute approximately 5% of the estimated 400
      projection neurons on each side of the L4 segment (Al-Khater and Todd, 2009).
      They are more numerous in cervical enlargement, but the total number of lamina I
      projection neurons in this region was not known. Here we have used paired
      injections of retrograde tracers into the brainstem to estimate the number of
      lamina I projection cells in the C7 segment. Our results suggest that there are
      approximately 215 lamina I projection cells per side, and that spinothalamic
      cells therefore make up approximately 42% of this population. The proportion of
      lamina I projection neurons labelled from PAG is higher in cervical than lumbar
      enlargement, while the proportion labelled from dorsal medulla is similar in the
      two regions. We also found that lamina I cells in L4 that project to the dorsal
      medulla are included in the population retrogradely labelled from LPb, thus
      confirming the estimate that there are around 400 lamina I projection cells in
      this segment.

PMID- 19854166
TI  - Identification of genetic polymorphisms of human OAT1 and OAT2 genes and their
      relationship to hOAT2 expression in human liver.
AB  - BACKGROUND: Organic anion transporters (OATs) play an essential role in the
      disposition of numerous organic anions. To clarify the interindividual variation
      in the function of OATs, genetic polymorphisms of the SLC22A6 and SLC22A7 in
      Korean subjects were investigated and associated with hepatic hOAT2 expression
      and the SLC22A7 genotype. METHODS: The genetic variants and their frequencies for
      the SLC22A6 and SLC22A7 genes in 50 Korean subjects were investigated by direct
      sequencing. The expression of hOAT2 protein from 34 human liver samples was
      examined by western blot analysis. RESULTS: Eight SNPs including 2 novel SNPs
      were identified in the SLC22A6 gene and eight SNPs including 4 novel SNPs were
      identified in the SLC22A7 gene. No amino acid alteration was found. Linkage
      disequilibrium (LD) analysis revealed that the SLC22A6 and SLC22A7 genes have
      separated single LD blocks and consist of a limited number of haplotypes (14
      haplotypes for SLC22A6 and 5 haplotypes for SLC22A7). The expression of the hOAT2
      protein varied 10-fold among 34 human livers but was not associated with the
      SLC22A7 genotype (p=0.16). CONCLUSIONS: The SLC22A7 genomic sequences showed low
      variability. A 10-fold variation in hOAT2 protein expression in the liver
      specimens was not correlated with SLC22A7 genotypes. These results suggest that
      genetic polymorphisms may not be a significant contributing factor to variations
      in the hOAT2 expression or hOAT2 transport activity.

PMID- 19854167
TI  - Cell cycle regulation in the inner ear sensory epithelia: role of cyclin D1 and
      cyclin-dependent kinase inhibitors.
AB  - Sensory hair cells and supporting cells of the mammalian cochlea and vestibular
      (balance) organs exit the cell cycle during embryogenesis and do not proliferate
      thereafter. Here, we have studied the mechanisms underlying the maintenance of
      the postmitotic state and the proliferative capacity of these cells. We provide
      the first evidence of the role of cyclin D1 in cell cycle regulation in these
      cells. Cyclin D1 expression disappeared from embryonic hair cells as
      differentiation started. The expression was transiently upregulated in cochlear
      hair cells early postnatally, paralleling the spatiotemporal pattern of
      unscheduled cell cycle re-entry of cochlear hair cells from the
      p19(Ink4d)/p21(Cip1) compound mutant mice. Cyclin D1 misexpression in vitro in
      neonatal vestibular HCs from these mutant mice triggered S-phase re-entry. Thus,
      cyclin D1 suppression is important for hair cell's quiescence, together with the
      maintained expression of cyclin-dependent kinase inhibitors. In contrast to hair
      cells, cyclin D1 expression was maintained in supporting cells when
      differentiation started. The expression continued during the neonatal period when
      supporting cells have been shown to re-enter the cell cycle upon stimulation with
      exogenous mitogens. Thereafter, the steep decline in supporting cell's
      proliferative activity paralleled with cyclin D1 downregulation. Thus, cyclin D1
      critically contributes to the proliferative plasticity of supporting cells. These
      data suggest that targeted cyclin D1 induction in supporting cells might be an
      avenue for proliferative regeneration in the inner ear.

PMID- 19854169
TI  - Penetration of azithromycin in experimental pleural empyema fluid.
AB  - There were no data about the extent of azithromycin penetration into the empyemic
      pleural fluid in humans and in experimental animals. An empyema was created via
      the intrapleural injection of an Escherichia coli solution into the pleural space
      of New Zealand white rabbits. After an empyema was verified by thoracocentesis,
      24h post inoculation, azithromycin (15 mg/kg) was administered intravenously.
      Antibiotic levels were determined in samples of pleural fluid and blood serum,
      collected serially at 2, 8, 24, 48 and 72 h, after administration. Azithromycin
      levels were estimated using an HPLC analytical method with fluorimetric
      detection. Azithromycin penetrated well into the empyemic pleural fluid,
      exhibiting a slower onset and decline compared to the corresponding blood serum
      levels. Equilibration between pleural fluid and blood serum compartments seemed
      to occur at 2h, with peak pleural fluid levels (C(maxpf) of 0.48 microg/ml)
      occurring 24h post administration and decreasing thereafter. Azithromycin peak
      serum concentration (C(maxserum) of 0.24 microg/ml) was observed 2h after
      administration and, thereafter, serum antibiotic levels remained lower than the
      corresponding pleural fluid ones. The area under the concentration versus time
      curve (AUC) and terminal half-life (T(1/2)) of azithromycin was three- to six
      fold and twofold higher, respectively, in the pleural fluid compared to the blood
      serum compartment. After intravenous administration, azithromycin penetrated well
      into the empyemic pleural fluid, exhibiting pleural fluid levels that are
      inhibitory for most erythromycin-sensitive pathogens causing empyema.

PMID- 19854170
TI  - Osteoclast migration on phosphorylated osteopontin is regulated by endogenous
      tartrate-resistant acid phosphatase.
AB  - Osteopontin (OPN) is a multifunctional protein implicated in cellular adhesion
      and migration. Phosphorylation has emerged as a post-translational modification
      important for certain biological activities of OPN. This study demonstrates that
      adhesion of isolated neonatal rat osteoclasts in vitro was augmented on bovine
      milk osteopontin (bmOPN) with post-translational modifications (PTMs) compared to
      human Escherichia-coli-derived recombinant OPN (hrOPN) without PTMs. The
      difference in adhesiveness between these OPN variants was more pronounced at low
      coating concentrations (</= 10 mug/ml). Both OPN forms adhered exclusively using
      a beta(3)-integrin. Partial (</=50%) dephosphorylation by tartrate-resistant acid
      phosphatase (TRAP) in vitro reduced osteoclast attachment to bmOPN to the same
      level as to hrOPN, demonstrating the importance of specific phosphorylations in
      OPN-dependent osteoclast adhesion. The involvement of PTMs of OPN in migration of
      primary rat and mouse osteoclasts was assessed on culture dishes coated with the
      different OPN forms and then overlaid with gold particles. Here, osteoclasts
      exhibited haptotactic migration on bmOPN but did not migrate on hrOPN. The
      presence of neutralizing antibodies to TRAP inhibited migration on bmOPN.
      Moreover, migration of osteoclasts isolated from TRAP-overexpressing transgenic
      mice was augmented on bmOPN, but not on hrOPN or type I collagen. These data
      collectively provide evidence in favor of a role for endogenous TRAP in
      regulating osteoclast migration on post-translationally modified OPN. In a tissue
      context, modulation of the phosphorylation level of OPN by extracellular
      phosphatases, e.g., TRAP, could regulate the extent of degradation such as depth
      and area at each bone resorption site by triggering osteoclast detachment and
      facilitate subsequent migration on the bone surface.

PMID- 19854168
TI  - The extracellular matrix in development and morphogenesis: a dynamic view.
AB  - The extracellular matrix (ECM) is synthesized and secreted by embryonic cells
      beginning at the earliest stages of development. Our understanding of ECM
      composition, structure and function has grown considerably in the last several
      decades and this knowledge has revealed that the extracellular microenvironment
      is critically important for cell growth, survival, differentiation and
      morphogenesis. ECM and the cellular receptors that interact with it mediate both
      physical linkages with the cytoskeleton and the bidirectional flow of information
      between the extracellular and intracellular compartments. This review considers
      the range of cell and tissue functions attributed to ECM molecules and summarizes
      recent findings specific to key developmental processes. The importance of ECM as
      a dynamic repository for growth factors is highlighted along with more recent
      studies implicating the 3-dimensional organization and physical properties of the
      ECM as it relates to cell signaling and the regulation of morphogenetic cell
      behaviors. Embryonic cell and tissue generated forces and mechanical signals
      arising from ECM adhesion represent emerging areas of interest in this field.

PMID- 19854171
TI  - Cholesterol efflux stimulates metalloproteinase-mediated cleavage of occludin and
      release of extracellular membrane particles containing its C-terminal fragments.
AB  - That changes in membrane lipid composition alter the barrier function of tight
      junctions illustrates the importance of the interactions between tetraspan
      integral tight junction proteins and lipids of the plasma membrane. Application
      of methyl-beta-cyclodextrin to both apical and basolateral surfaces of MDCK cell
      monolayers for 2 h, results in an approximately 80% decrease in cell cholesterol,
      a fall in transepithelial electrical resistance, and a 30% reduction in cell
      content of occludin, with a smaller reduction in levels of claudins-2, -3, and 
      7. There were negligible changes in levels of actin and the two non-tight
      junction membrane proteins GP-135 and caveolin-1. While in untreated control
      cells breakdown of occludin, and probably other tight junction proteins, is
      mediated by intracellular proteolysis, our current data suggest an alternative
      pathway whereby in a cholesterol-depleted membrane, levels of tight junction
      proteins are decreased via direct release into the intercellular space as
      components of membrane-bound particles. Occludin, along with two of its
      degradation products and several claudins, increases in the basolateral medium
      after incubation with methyl-beta-cyclodextrin for 30 min. In contrast caveolin-1
      is detected only in the apical medium after adding methyl-beta-cyclodextrin.
      Release of occludin and its proteolytic fragments continues even after removal of
      methyl-beta-cyclodextrin. Sedimentation and ultrastructural studies indicate that
      the extracellular tight junction proteins are associated with the membrane-bound
      particles that accumulate between adjacent cells. Disruption of the actin
      filament network by cytochalasin D did not diminish methyl-beta-cyclodextrin
      induced release of tight junction proteins into the medium, suggesting that the
      mechanism underlying their formation is not actin-dependent. The 41- and 48-kDa C
      terminal occludin fragments formed during cholesterol depletion result from the
      action of a GM6001-sensitive metalloproteinase(s) at some point in the path
      leading to release of the membrane particles.

PMID- 19854172
TI  - Detection, identification and molecular typing of Leishmania major in Phlebotomus
      papatasi from a focus of zoonotic cutaneous leishmaniasis in central of Iran.
AB  - Leishmania major is the causative agent and Phlebotomus papatasi is the main
      vector of rural zoonotic cutaneous leishmaniasis (ZCL) in Iran and elsewhere.
      Nested PCR protocols were used to amplify a region of the ribosomal RNA amplicon
      of Leishmania (ITS1-5.8S rRNA gene) in female P. papatasi. In the current
      investigation, L. major was found in Natanz, Isfahan province in centre of Iran,
      in a focus of rural ZCL. Ten (1.8%) out of 549 female P. papatasi was found to be
      infected with L. major based on the PCR detection and sequencing of parasite ITS
      rDNA. Nine (1.8%) out of 498 female P. papatasi infected with L. major came from
      animal shelters, inside houses and yards. And one (1.9%) out of 51 female P.
      papatasi infected with L. major came from gerbil borrows. Infection rates were
      higher for females containing red blood meals, large eggs (semi-mature and
      mature) than for those without either blood meals or eggs. From the 10 infections
      detected three different haplotypes of L. major were identified. Two haplotypes
      were found to be novel. The other haplotypes of L. major was found to be
      identical to that of isolates of L. major from Iran and in elsewhere using
      GenBank data. Comparisons of infection rates between habitats will be inaccurate
      when the proportions of blood-fed and gravid flies differ among sandfly samples.

PMID- 19854173
TI  - Toxoplasma gondii: Simple duplex RT-PCR assay for detecting SAG1 and BAG1 genes
      during stage conversion in immunosuppressed mice.
AB  - Toxoplasmic encephalitis (TE) is caused by reactivation of dormant bradyzoites
      into rapidly dividing tachyzoites of the apicomplexan parasite Toxoplasma gondii
      in immune-compromised hosts. Diagnosis of this life-threatening disease is
      complicated, since it is difficult to distinguish between these two stages. It
      is, therefore, mainly based on a test positive for T. gondii antibodies, and
      specific clinical symptoms. We developed a duplex RT-PCR to detect the expression
      of bradyzoite (BAG1) and tachyzoite (SAG1) specific genes simultaneously during
      tachyzoite/bradyzoite stage conversion. The conversion reaction was observed in
      many organs of experimental mice, indicated by tachyzoites in the cerebrum,
      cerebellum, heart and lung, beginning in week 1 after the suppression period, and
      continuing until the end. Bradyzoites were also detected in nearly all organs
      throughout the study, suggesting that during the reactivation period, bradyzoites
      not only escape from cysts and reinvade neighboring cells as tachyzoites, but are
      also driven into developing new bradyzoites. The results of our study show that
      duplex RT-PCR is an easy, rapid, sensitive, and reproducible method, which is
      particularly valuable when numerous samples must be analyzed. This technique may
      usefully serve as an alternate tool for diagnosing TE in severely
      immunocompromised patients.

PMID- 19854174
TI  - Changes in macrophage membrane properties during early Leishmania amazonensis
      infection differ from those observed during established infection and are
      partially explained by phagocytosis.
AB  - Understanding the impact of intracellular pathogens on the behavior of their host
      cells is key to designing new interventions. We are interested in how Leishmania
      alters the electrical function of the plasma membrane of the macrophage it
      infects. The specific question addressed here is the impact of Leishmania
      infection on macrophage membrane properties during the first 12h post-infection.
      A decrease of 29% in macrophage membrane capacitance at 3h post-infection
      indicates that the phagolysosome membrane is donated on entry by the macrophage
      plasma membrane. Macrophage membrane potential depolarized during the first 12h
      post-infection, which associated with a decreased inward potassium current
      density, changed in inward rectifier conductance and increased outward potassium
      current density. Decreased membrane capacitance and membrane potential, with no
      changes in ion current density, were found in macrophages after phagocytosis of
      latex beads. Therefore we suggest that the macrophage membrane changes observed
      during early Leishmania infection appear to be associated with the phagocytic and
      activation processes.

PMID- 19854175
TI  - Leishmania (Leishmania) infantum/chagasi: Histopathological aspects of the skin
      in naturally infected dogs in two endemic areas.
AB  - In the New World, visceral leishmaniasis (VL), which is a progressive disease and
      frequently fatal, is caused by Leishmania (Leishmania) infantum/chagasi. It is
      endemic in many regions of Brazil and occasionally occurs in non-endemic regions
      when dogs from an endemic area are introduced. The aim of the present study is to
      compare different skin infection patterns of dogs from two leishmaniasis endemic
      areas. A histological analysis of dogs from Campo Grande, Mato Grosso do Sul
      state, a region where epidemic episodes are currently taking place, showed dermic
      inflammatory infiltrates, composed of numerous vacuolated parasitized
      macrophages, few lymphocytes, plasma cells and many degranulated mast cells. In
      the other region of the study, Sao Luis, Maranhao state, the skin of dogs
      presented a remarkable inflammatory reaction composed mainly of plasma cells,
      lymphocytes and very few parasites. We concluded that there is a difference in
      the skin lesion patterns of dogs with leishmaniasis that is directly related to
      the endemic area where the animals live.

PMID- 19854176
TI  - The retinal structure of channelrhodopsin-2 assessed by resonance Raman
      spectroscopy.
AB  - Channelrhodopsin-2 mediates phototaxis in green algae by acting as a light-gated
      cation channel. As a result of this property, it is used as a novel optogenetic
      tool in neurophysiological applications. Structural information is still scant
      and we present here the first resonance Raman spectra of channelrhodopsin-2.
      Spectra of detergent solubilized and lipid-reconstituted protein were recorded
      under pre-resonant conditions to exclusively probe retinal in its electronic
      ground state. All-trans retinal was identified to be the favoured configuration
      of the chromophore but significant contributions of 13-cis were detected. Pre
      illumination hardly changed the isomeric composition but small amounts of
      presumably 9-cis retinal were found in the light-adapted state. Spectral analysis
      suggested that the Schiff base proton is strongly hydrogen-bonded to a nearby
      water molecule.

PMID- 19854177
TI  - Mechanisms of COPI vesicle formation.
AB  - Coat Protein I (COPI) is one of the most intensely investigated coat complexes.
      Numerous studies have contributed to a general understanding of how coat proteins
      act to initiate intracellular vesicular transport. This review highlights key
      recent findings that have shaped our current understanding of how COPI vesicles
      are formed.

PMID- 19854178
TI  - Diffusion of a membrane protein, Tat subunit Hcf106, is highly restricted within
      the chloroplast thylakoid network.
AB  - The thylakoid membrane forms stacked thylakoids interconnected by 'stromal'
      lamellae. Little is known about the mobility of proteins within this system. We
      studied a stromal lamellae protein, Hcf106, by targeting an Hcf106-GFP fusion
      protein to the thylakoids and photobleaching. We find that even small regions
      fail to recover Hcf106-GFP fluorescence over periods of up to 3 min after
      photobleaching. The protein is thus either immobile within the thylakoid
      membrane, or its diffusion is tightly restricted within distinct regions.
      Autofluorescence from the photosystem II light-harvesting complex in the granal
      stacks likewise fails to recover. Integral membrane proteins within both the
      stromal and granal membranes are therefore highly constrained, possibly forming
      'microdomains' that are sharply separated.

PMID- 19854179
TI  - A conserved sequence in caveolin-1 is both necessary and sufficient for caveolin
      polarity and cell directional migration.
AB  - Caveolin-1 (Cav-1) plays an important role in the organization of signaling
      molecules involved in a variety of signaling pathways, including those mediating
      cell motility. Here we show that amino acids K47-K57 of Cav-1 are a highly
      conserved sequence in Cav-1 and Cav-3 proteins, and that expression of either K47
      K57 deletion Cav-1 mutant or wild-type Cav-2 that lacks this sequence exhibits a
      non-polarized distribution pattern. Expression of K47-K57 in Cav-2 leads to Cav-2
      polarity, suggesting that expression of K47-K57 is sufficient to direct caveolin
      polarity. Importantly, we show that expression of this sequence is both necessary
      and sufficient to promote cell directional migration. Thus, our results support
      the conclusion that Cav-1 polarity is critical for cell directional migration.

PMID- 19854180
TI  - The KDEL receptor: new functions for an old protein.
AB  - The KDEL receptor is a seven-transmembrane-domain protein that was first
      described about 20 years ago. Its well-known function is to retrotransport
      chaperones from the Golgi complex to the endoplasmic reticulum. Recent studies,
      however, have suggested that the KDEL receptor has additional functions. Indeed,
      we have demonstrated that chaperone-bound KDEL receptor triggers the activation
      of Src family kinases on the Golgi complex. This activity is essential in the
      regulation of Golgi-to-plasma membrane transport. However, the identification of
      different KDEL receptor interactors that are inconsistent with these established
      functions opens the possibility of further receptor activities.

PMID- 19854181
TI  - Luteolin, a food-derived flavonoid, suppresses adipocyte-dependent activation of
      macrophages by inhibiting JNK activation.
AB  - Interaction between adipocytes and macrophages contributes to the development of
      insulin resistance in obese adipose tissues. In this study, we examined whether
      luteolin, food-derived flavonoid, could suppress the production of inflammatory
      mediators of the interaction between adipocytes and macrophages. Experiments
      using a coculture system of adipocytes and macrophages showed that luteolin
      suppressed the production of inflammatory mediators. In addition, activated
      macrophages were targets for the suppressive effect of luteolin. Luteolin
      inhibited the phosphorylation of JNK and suppressed the production of
      inflammatory mediators in the activated macrophages. The findings indicate that
      luteolin can inhibit the interaction between adipocytes and macrophages to
      suppress the production of inflammatory mediators, suggesting that luteolin is a
      valuable food-derived compound for the treatment of metabolic syndrome.

PMID- 19854183
TI  - Systems biology of lipid metabolism: from yeast to human.
AB  - Lipid metabolism is highly relevant as it plays a central role in a number of
      human diseases. Due to the highly interactive structure of lipid metabolism and
      its regulation, it is necessary to apply a holistic approach, and systems biology
      is therefore well suited for integrated analysis of lipid metabolism. In this
      paper it is demonstrated that the yeast Saccharomyces cerevisiae serves as an
      excellent model organism for studying the regulation of lipid metabolism in
      eukaryotes as most of the regulatory structures in this part of the metabolism
      are conserved between yeast and mammals. Hereby yeast systems biology can assist
      to improve our understanding of how lipid metabolism is regulated.

PMID- 19854184
TI  - The crystal structure of a hyperthermoactive exopolygalacturonase from Thermotoga
      maritima reveals a unique tetramer.
AB  - The exopolygalacturonase from Thermotoga maritima is the most thermoactive and
      thermostable pectinase known to date. Here we present its crystal structure at
      2.05A resolution. High structural homology around the active site allowed us to
      propose a model for substrate binding, explaining the exo-cleavage activity and
      specificity for non-methylated saturated galacturonate at the non-reducing end.
      Furthermore, the structure reveals unique features that contribute to the
      formation of stable tetramers in solution. Such an oligomerization has not been
      observed before for polygalacturonases.

PMID- 19854182
TI  - Clathrin and AP1B: key roles in basolateral trafficking through trans-endosomal
      routes.
AB  - Research following introduction of the MDCK model system to study epithelial
      polarity (1978) led to an initial paradigm that posited independent roles of the
      trans Golgi network (TGN) and recycling endosomes (RE) in the generation of,
      respectively, biosynthetic and recycling routes of plasma membrane (PM) proteins
      to apical and basolateral PM domains. This model dominated the field for 20
      years. However, studies over the past decade and the discovery of the involvement
      of clathrin and clathrin adaptors in protein trafficking to the basolateral PM
      has led to a new paradigm. TGN and RE are now believed to cooperate closely in
      both biosynthetic and recycling trafficking routes. Here, we critically review
      these recent advances and the questions that remain unanswered.

PMID- 19854185
TI  - Thermodynamic analysis of substrate induced domain closure of 3-phosphoglycerate
      kinase.
AB  - The energetic changes accompanying domain closure of 3-phosphoglycerate kinase, a
      typical hinge-bending enzyme, were assessed. Calorimetric titrations of the
      enzyme with each substrate, both in the absence and presence of the other one,
      provide information not only about the energetics of substrate binding, but of
      the associated conformational changes, including domain closure. Our results
      suggest that conformational rearrangements in the hinge generated by binding of
      both substrates provide the main driving force for domain closure overcoming the
      slightly unfavourable contact interactions between the domains.

PMID- 19854186
TI  - Formation and regulation of lipid microdomains in cell membranes: theory,
      modeling, and speculation.
AB  - Compositional lipid microdomains ("lipid rafts") in plasma membranes are believed
      to be important components of many cellular processes. The biophysical mechanisms
      by which cells regulate the size, lifetime, and spatial localization of these
      domains are rather poorly understood at the moment. Over the years, experimental
      studies of raft formation have inspired several phenomenological theories and
      speculations incorporating a wide variety of thermodynamic assumptions regarding
      lipid-lipid and lipid-protein interactions, and the potential role of active
      cellular processes on membrane structure. Here we critically review and discuss
      these theories, models, and speculations, and present our view on future
      directions.

PMID- 19854188
TI  - Evodiamine inhibits adipogenesis via the EGFR-PKCalpha-ERK signaling pathway.
AB  - The molecular mechanism of the anti-adipogenic effect of evodiamine (which has
      several capsaicin-like pharmacological actions) was investigated. The evodiamine
      effect was not blocked by the specific TRPV1 antagonist capsazepine in 3T3-L1
      preadipocytes, whereas its effect was greatly curtailed by inhibitors of protein
      kinase C (PKC) and epidermal growth factor receptor (EGFR). Signal analyses
      showed that evodiamine stimulated the phosphorylation of EGFR, PKCalpha, and ERK,
      all of which were reduced by an EGFR inhibitor. Silencing experiments of EGFR
      mRNA supported the involvement of these signaling molecules in the inhibitory
      effect of evodiamine. An unidentified mechanism whereby evodiamine inhibits
      adipogenesis via the EGFR-PKCalpha-ERK signaling pathway was revealed.

PMID- 19854187
TI  - The role of glycophosphatidylinositol anchor in the amplification of the scrapie
      isoform of prion protein in vitro.
AB  - Transmissible spongiform encephalopathies are associated with an autocatalytic
      conversion of normal prion protein, PrP(C), to a protease-resistant form, PrPres.
      This autocatalytic reaction can be reproduced in vitro using a procedure called
      protein misfolding cyclic amplification (PMCA). Here we show that, unlike brain
      derived PrP(C), bacterially-expressed recombinant prion protein (rPrP) is a poor
      substrate for PrPres amplification in a standard PMCA reaction. The differences
      between PrP(C) and rPrP appear to be due to the lack of the
      glycophosphatidylinositol anchor in the recombinant protein. These findings shed
      a new light on prion protein conversion process and have important implications
      for the efforts to generate synthetic prions for structural and biophysical
      studies.

PMID- 19854189
TI  - Cocaine- and amphetamine-regulated transcript mediates the actions of
      cholecystokinin on rat vagal afferent neurons.
AB  - BACKGROUND & AIMS: Cholecystokinin (CCK) acts on vagal afferent neurons to
      inhibit food intake and gastric emptying; it also increases expression of the
      neuropeptide cocaine- and amphetamine-regulated transcript (CART), but the
      significance of this is unknown. We investigated the role of CARTp in vagal
      afferent neurons. METHODS: Release of CART peptide (CARTp) from cultured vagal
      afferent neurons was determined by enzyme-linked immunosorbent assay. Expression
      of receptors and neuropeptides in rat vagal afferent neurons in response to CARTp
      was studied using immunohistochemistry and luciferase promoter reporter
      constructs. Effects of CARTp and CCK were studied on food intake. RESULTS: CCK
      stimulated CARTp release from cultured nodose neurons. CARTp replicated the
      effect of CCK in stimulating expression of Y2R and of CART itself in these
      neurons in vivo and in vitro, but not in inhibiting cannabinoid-1, melanin
      concentrating hormone, and melanin-concentrating hormone-1 receptor expression.
      Effects of CCK on Y2R and CART expression were reduced by CART small interfering
      RNA or brefeldin A. Exposure of rats to CARTp increased the inhibitory action of
      CCK on food intake after short-, but not long-duration, fasting. CONCLUSIONS: The
      actions of CCK in stimulating CART and Y2R expression in vagal afferent neurons
      and in inhibiting food intake are augmented by CARTp; CARTp is released by CCK
      from these neurons, indicating that it acts as an autocrine excitatory mediator.

PMID- 19854191
TI  - A novel prolactin-like protein (PRL-L) gene in chickens and zebrafish: cloning
      and characterization of its tissue expression.
AB  - In this study, a full-length cDNA encoding a prolactin-like protein (PRL-L) was
      cloned from chicken brain tissues using RT-PCR. This putative PRL-L precursor has
      225 amino acids in length and shares 30-35% amino acid sequence identity with
      prolactin (PRL) of chicken, zebrafish, Xenopus, rat and human. Using RT-PCR, the
      mRNA expression of PRL-L in chicken tissues was further examined. Unlike the
      predominant expression of PRL in pituitary, PRL-L was found to be widely
      expressed in adult chicken extra-pituitary tissues with only minimal expression
      detected in pituitary. In day-7 chicken embryos, the expression of PRL-L, but not
      PRL, was also detected in all extra-pituitary tissues examined. In line with this
      finding, the 5'-flanking region of chicken PRL-L (cPRL-L) gene, but not PRL gene,
      displayed a strong promoter activity in cultured DF-1 cell (a chicken embryo
      fibroblast cell line), suggesting that the basal expression of PRL-L gene is
      controlled by a transcriptional regulatory mechanism different from that of PRL
      gene. As the same findings in chickens, PRL-like protein(s), which share high
      amino acid sequence (42-86%) identity with chicken PRL-L, was identified in
      several non-mammalian vertebrate species including zebra finch, tiger puffer,
      green puffer and zebrafish. RT-PCR assay demonstrated that zebrafish PRL-L,
      similar to chicken PRL-L, is expressed in extra-pituitary tissues including
      brain, gill, muscle, ovary and testis. Taken together, these findings strongly
      suggest that a novel PRL-like protein exists in some non-mammalian vertebrates
      and may play an important role in target tissues, such as extra-pituitary tissues
      of chickens and zebrafish.

PMID- 19854190
TI  - Maternal androgen levels during pregnancy are associated with early-life growth
      in Geoffroy's marmosets, Callithrix geoffroyi.
AB  - Fetal development is a critical period of physical development, and factors in
      the intrauterine environment can cause lasting effects on the growth and
      development of offspring. There is little research evaluating organizational
      effects of early androgen exposure of endogenous maternal origins on the prenatal
      and postnatal growth of offspring. We evaluated the association between maternal
      androgen levels during gestation and pre- and postnatal growth of offspring.
      Maternal androgen levels in marmoset females were measured using enzyme
      immunoassays of urine samples acquired during 18 pregnancies. Somatic
      measurements of the resulting 25 viable offspring were taken on postnatal days
      (PND) 2, 30, 60, 120, 180, 240, and 300. Maternal androgen levels during the
      first trimester were negatively associated with weight, body length, and several
      girth measurements (i.e., torso, head, chest, and arm circumference) of offspring
      on PND 2. First trimester maternal androgen was also negatively associated with
      physical growth during early and late infancy but seemed to be positively
      associated with a rebound in juvenile growth. Exposure to maternal androgen
      during early gestation led to both a reduction in birth weight and postnatal
      catch-up for both males and females, equally. Fetal growth retardation and the
      reprogramming of metabolic tissues by exposure to prenatal androgen could be
      mediating factors of suppressed postnatal growth.

PMID- 19854192
TI  - Fish with thermolabile sex determination (TSD) as models to study brain sex
      differentiation.
AB  - As fish are ectothermic animals, water temperature can affect their basic
      biological processes such as larval development, growth and reproduction. Similar
      to reptiles, the incubation temperature during early phases of development is
      capable to modify sex ratios in a large number of fish species. This phenomenon,
      known as thermolabile sex determination (TSD) was first reported in Menidia
      menidia, a species belonging to the family Atherinopsidae. Since then, an
      increasing number of fish have also been found to exhibit TSD. Traditionally,
      likewise in reptiles, several TSD patterns have been described in fish, however
      it has been recently postulated that only one, females at low temperatures and
      males at high temperatures, may represent the "real" or "true" TSD. Many studies
      regarding the influence of temperature on the final sex ratios have been focused
      on the expression and activity of gonadal aromatase, the enzyme involved in the
      conversion of androgens into estrogens and encoded by the cyp19a1a gene. In this
      regard, teleost fish, may be due to a whole genome duplication event, produce
      another aromatase enzyme, commonly named brain aromatase, encoded by the cyp19a1b
      gene. Contrary to what has been described in other vertebrates, fish exhibit very
      high levels of aromatase activity in the brain and therefore they synthesize high
      amounts of neuroestrogens. However, its biological significance is still not
      understood. In addition, the mechanism whereby temperature can induce the
      development of a testis or an ovary still remains elusive. In this context the
      present review is aimed to discuss several theories about the possible role of
      brain aromatase using fish as models. The relevance of brain aromatase and
      therefore of neuroestrogens as the possible cue for gonadal differentiation is
      raised. In addition, the possible role of brain aromatase as the way to keep the
      high levels of neurogenesis in fish is also considered. Several key examples of
      how teleosts and aromatase regulation can offer more insight into basic
      mechanisms of TSD are also reviewed.

PMID- 19854193
TI  - Production, characterization, and applications of mouse monoclonal antibodies
      against gonadotropin, somatolactin, and prolactin from common carp (Cyprinus
      carpio).
AB  - The gonadotropin alpha subunit (cGTH alpha), gonadotropin II beta subunit (cGTHII
      beta), somatolactin (cSL), and prolactin (cPRL) were isolated from the
      pituitaries of common carps, purified by traditional chromatographic analysis,
      identified by mass-chromatographic analysis, and used as immunogens in the B
      lymphocyte hybridoma technique. Totally, 7, 11, 17, and 8 hybridoma cell lines
      were established, which were able to stably secrete monoclonal antibodies (mAbs)
      against cGTH alpha, cGTHII beta, cSL, and cPRL, and designated as FMU-cGTH alpha
      1-7, FMU-cGTHII beta 1-11, FMU-cSL 1-17, and FMU-cPRL 1-8, respectively. The
      isotype, titer, and specificity were identified by enzyme-linked immunosorbent
      assay (ELISA), Western blot, and immunohistochemical staining, respectively, and
      application of these mAbs in the aforementioned tests has been proved.
      Furthermore, sensitive sandwich-ELISA systems for quantitative detection of the
      hormones mentioned above were also developed.

PMID- 19854194
TI  - Is there a leptin gene in the chicken genome? Lessons from phylogenetics,
      bioinformatics and genomics.

PMID- 19854195
TI  - "Binge" drinking experience in adolescent mice shows sex differences and elevated
      ethanol intake in adulthood.
AB  - Binge drinking, defined as achieving blood ethanol concentrations (BEC) of 80
      mg%, has been increasing in adolescents and was reported to predispose later
      physical dependence. The present experiments utilized an animal model of binge
      drinking to compare the effect of ethanol "binge" experience during adolescence
      or adulthood on subsequent ethanol intake in male and female C57BL/6 mice.
      Adolescent and adult mice were initially exposed to the scheduled high alcohol
      consumption procedure, which produces BECs that exceed the levels for binge
      drinking following a 30-min ethanol session every third day. Ethanol intake and
      BECs were significantly higher in the adolescent ( approximately 3 g/kg, 199 mg%)
      versus adult ( approximately 2 g/kg, 135 mg%) mice during the first three ethanol
      sessions, but were more equivalent during the final two ethanol sessions (1.85
      2.0 g/kg, 129-143 mg%). Then, separate groups of the ethanol-experienced mice
      were tested with ethanol naive adolescent and adult mice for 2-h limited access
      (10% and 20% solutions) or 24-h (5%, 10% and 20% solutions) ethanol preference
      drinking. Limited access ethanol intake was significantly higher in female versus
      male mice, but was not altered by age or ethanol experience. In contrast, 24-h
      ethanol intake was significantly higher in the adolescent versus adult mice and
      in female versus male mice. Furthermore, binge drinking experience in the
      adolescent mice significantly increased subsequent ethanol intake, primarily due
      to intake in female mice. Thus, adolescent binge drinking significantly increased
      unlimited ethanol intake during adulthood, with female mice more susceptible to
      this effect.

PMID- 19854196
TI  - Phylogenetic relationships of haemosporidian parasites in New World
      Columbiformes, with emphasis on the endemic Galapagos dove.
AB  - DNA-sequence analyses of avian haemosporidian parasites, primarily of passerine
      birds, have described the phylogenetic relationships of major groups of these
      parasites, which are in general agreement with morphological taxonomy. However,
      less attention has been paid to haemosporidian parasites of non-passerine birds
      despite morphological and DNA-sequence evidence for unique clades of parasites in
      these birds. Detection of haemosporidian parasites in the Galapagos archipelago
      has raised conservation concerns and prompted us to characterise the origins and
      diversity of these parasites in the Galapagos dove (Zenaida galapagoensis). We
      used partial mitochondrial cytochrome b (cyt b) and apicoplast caseinolytic
      protease C (ClpC) genes to develop a phylogenetic hypothesis of relationships of
      haemosporidian parasites infecting New World Columbiformes, paying special
      attention to those parasites infecting the endemic Galapagos dove. We identified
      a well-supported and diverse monophyletic clade of haemosporidian parasites
      unique to Columbiformes, which belong to the sub-genus Haemoproteus
      (Haemoproteus). This is a sister clade to all the Haemoproteus (Parahaemoproteus)
      and Plasmodium parasites so far identified from birds as well as the Plasmodium
      parasites of mammals and reptiles. Our data suggest that the diverse Haemoproteus
      parasites observed in Galapagos doves are not endemic to the archipelago and
      likely represent multiple recent introductions.

PMID- 19854197
TI  - Comparison of the results obtained by ELISA and surface plasmon resonance for the
      determination of antibody affinity.
AB  - The aim of this study was to compare the affinity values obtained for a
      monoclonal antibody/antigen complex using two different techniques, surface
      plasmon resonance (SPR) and an enzyme linked immunosorbent assay (ELISA) approach
      recently described by Bobrovnik S.A. and by Stevens F.J. These two techniques can
      be used in particular to determine the equilibrium dissociation constant, K(D),
      of the complex in solution or on a surface. Bobrovnik's method gives two K(D)
      values that differ by a factor of 100, demonstrating that two populations of
      complexes are present in solution. In an initial step, one protein binds
      relatively weakly to the other (high K(D)) and this is followed by a
      conformational change in the most flexible portion of the antigen, which
      increases the affinity (low K(D)). Only the higher of the two K(D) values can be
      detected when complex formation in solution is investigated using SPR, because
      the interaction measured concerns the fibronectin/antibody complexes of lowest
      affinity. In contrast, when measuring association at the sensor surface, SPR
      gives an average result between the two K(D) values because complexes
      corresponding to both affinities can form in this situation. The constants that
      characterise the kinetics of the fibronectin-antibody interaction obtained by SPR
      and ELISA are therefore different, because the methods do not allow the same
      phenomena to be observed. However they are consistent and complementary.

PMID- 19854198
TI  - Mutations at the same amino acid in myosin that cause either skeletal or cardiac
      myopathy have distinct molecular phenotypes.
AB  - To date, more than 230 disease-causing mutations have been linked to the
      slow/cardiac muscle myosin gene, beta-MyHC (MYH7). Most of these mutations are
      located in the globular head region of the protein and result in
      cardiomyopathies. Recently, however, a number of novel disease-causing mutations
      have been described in the long, alpha-helical, coiled coil tail region of the
      beta-MyHC protein. Mutations in this region are of particular interest because
      they are associated with a multitude of human diseases, including both cardiac
      and skeletal myopathies. Here, we attempt to dissect the mechanism(s) by which
      mutations in the rod region of beta-MyHC can cause a variety of diseases by
      analyzing two mutations at a single amino acid (R1500P and R1500W) which cause
      two distinct diseases (Laing-type early-onset distal myopathy and dilated
      cardiomyopathy, respectively). For diseases linked to the R1500 residue, we find
      that each mutation displays distinct structural, thermodynamic, and functional
      properties. Both R1500P and R1500W cause a decrease in thermodynamic stability,
      although the R1500W phenotype is more severe. Both mutations also affect filament
      assembly, with R1500P causing an additional decrease in filament stability. In
      addition to furthering our understanding of the mechanism of pathogenesis for
      each of these diseases, these data also suggest how the variance in molecular
      phenotype may be associated with the variance in clinical phenotype present with
      mutations in the beta-MyHC rod.

PMID- 19854199
TI  - Calcineurin protects the heart in a murine model of dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a relatively common disease with a poor
      prognosis. Given that the only meaningful treatment for DCM is cardiac
      transplantation, investigators have explored the underlying molecular mechanisms
      of this disease in the hopes of identifying novel therapeutic targets. One such
      target is the serine-threonine phosphatase calcineurin, a Ca2+-activated
      signaling factor that is known to regulate the cardiac hypertrophic program,
      although its role in DCM is currently unknown. In order to address this issue, we
      crossed muscle lim protein (MLP) knock-out mice-a murine model of DCM-with
      calcineurin A beta ko mice, which lack the stress responsive isoform of
      calcineurin that critically regulates the cardiac hypertrophic response.
      Interestingly, the majority (73%) of the MLP/calcineurin A beta double knock-out
      mice died within 20 days of birth with signs of cardiomyopathy. Ultrastructural
      examination revealed enhanced cardiomyocyte apoptosis and necrosis in the
      postnatal myocardium of these mice. The MLP/calcineurin A beta double knock-out
      mice that survived until adulthood showed reduced left ventricular function,
      enhanced apoptotic and necrotic cardiomyocyte death and augmented myocardial
      fibrosis compared to various control groups. Antithetically, mild overexpression
      of activated calcineurin in the mouse heart improved function and adverse
      remodeling in MLP knock-out mice. Collectively, these results reveal an important
      and previously unrecognized protective function of endogenous myocardial
      calcineurin in a mouse model of dilated cardiomyopathy.

PMID- 19854200
TI  - Effects of myosin heavy chain manipulation in experimental heart failure.
AB  - The myosin heavy chain (MHC) isoforms, alpha- and beta-MHC, are expressed in
      developmental- and chamber-specific patterns. Healthy human ventricle contains
      approximately 2-10% alpha-MHC and these levels are reduced even further in the
      failing ventricle. While down-regulation of alpha-MHC in failing myocardium is
      considered compensatory, we previously demonstrated that persistent transgenic
      (TG) alpha-MHC expression in the cardiomyocytes is cardioprotective in rabbits
      with tachycardia-induced cardiomyopathy (TIC). We sought to determine if this
      benefit extends to other types of experimental heart failure and focused on two
      models relevant to human heart failure: myocardial infarction (MI) and left
      ventricular pressure overload. TG and nontransgenic rabbits underwent either
      coronary artery ligation at 8 months or aortic banding at 10 days of age. The
      effects of alpha-MHC expression were assessed at molecular, histological and
      organ levels. In the MI experiments, we unexpectedly found modest functional
      advantages to alpha-MHC expression. In contrast, despite subtle benefits in TG
      rabbits subjected to aortic banding, cardiac function was minimally affected. We
      conclude that the benefits of persistent alpha-MHC expression depend upon the
      mechanism of heart failure. Importantly, in none of the scenarios studied did we
      find any detrimental effects associated with persistent alpha-MHC expression.
      Thus manipulation of MHC composition may be beneficial in certain types of heart
      failure and does not appear to compromise heart function in others. Future
      considerations of myosin isoform manipulation as a therapeutic strategy should
      consider the underlying etiology of cardiac dysfunction.

PMID- 19854201
TI  - Structural analysis of cysteine S-nitrosylation: a modified acid-based motif and
      the emerging role of trans-nitrosylation.
AB  - S-Nitrosylation, the selective and reversible addition of nitric oxide (NO)
      moiety to cysteine (Cys) sulfur in proteins, regulates numerous cellular
      processes. In recent years, proteomic approaches that are capable of identifying
      nitrosylated Cys residues have been developed. However, the features underlying
      the specificity of Cys modification with NO remain poorly defined. Previous
      studies suggested that S-nitrosylated Cys may be flanked by an acid-base motif or
      hydrophobic areas and show high reactivity, low pK(a), and high sulfur atom
      exposure. In the current study, we prepared an extensive, manually curated data
      set of proteins with S-nitrosothiols, accounting for a variety of biochemical
      functions, organisms of origin, and physiological responses to NO. Analysis of
      this generic NO-Cys data set revealed that proximal acid-base motif, Cys pK(a),
      sulfur atom exposure, and Cys conservation or hydrophobicity in the vicinity of
      the modified Cys do not define the specificity of S-nitrosylation. Instead, this
      analysis revealed a revised acid-base motif, which is located more distantly to
      the Cys and has its charged groups exposed. We hypothesize that, rather than
      being strictly used for direct activation of Cys, the modified acid-base motif is
      engaged in protein-protein interactions thereby contributing to trans
      nitrosylation as an important and widespread mechanism for reversible
      modification of Cys with NO moiety. For proteins lacking the revised motif, we
      discuss alternative mechanisms including a potential role of nitrosoglutathione
      as a trans-acting agent.

PMID- 19854202
TI  - Triosephosphate isomerase: 15N and 13C chemical shift assignments and
      conformational change upon ligand binding by magic-angle spinning solid-state NMR
      spectroscopy.
AB  - Microcrystalline uniformly (13)C,(15)N-enriched yeast triosephosphate isomerase
      (TIM) is sequentially assigned by high-resolution solid-state NMR (SSNMR).
      Assignments are based on intraresidue and interresidue correlations, using
      dipolar polarization transfer methods, and guided by solution NMR assignments of
      the same protein. We obtained information on most of the active-site residues
      involved in chemistry, including some that were not reported in a previous
      solution NMR study, such as the side-chain carbons of His95. Chemical shift
      differences comparing the microcrystalline environment to the aqueous environment
      appear to be mainly due to crystal packing interactions. Site-specific
      perturbations of the enzyme's chemical shifts upon ligand binding are studied by
      SSNMR for the first time. These changes monitor proteinwide conformational
      adjustment upon ligand binding, including many of the sites probed by solution
      NMR and X-ray studies. Changes in Gln119, Ala163, and Gly210 were observed in our
      SSNMR studies, but were not reported in solution NMR studies (chicken or yeast).
      These studies identify a number of new sites with particularly clear markers for
      ligand binding, paving the way for future studies of triosephosphate isomerase
      dynamics and mechanism.

PMID- 19854203
TI  - The dominance of symmetry in the evolution of homo-oligomeric proteins.
AB  - The fact that aggregates of identical protein molecules are usually symmetric has
      remained an enigma. An idealized model of a soluble monomeric protein was
      constructed and accompanied through a simulated evolutionary process resulting in
      dimerization, in order to elucidate this peculiarity. The model showed that the
      probability of a symmetric association is by a factor of 100 or above higher than
      the probability of an asymmetric one. Unexpectedly, symmetry prevails in the
      dimer initiation phase much more than in the dimer improvement phase of
      evolution. The result is clear-cut and robust against a broad spectrum of model
      inadequacies. It rationalizes the predominance of symmetric homo-oligomers.

PMID- 19854206
TI  - Some model based considerations on observing generation times for communicable
      diseases.
AB  - The generation time of an infectious disease is usually defined as the time from
      the moment one person becomes infected until that person infects another person.
      The concept is similar to "generation gap" in demography, with new infections
      replacing births in a population. Originally applied to diseases such as measles
      where at least the first generations are clearly discernible, the concept has
      recently been extended to other diseases, such as influenza, where time order of
      infections is usually much less apparent. By formulating the relevant statistical
      questions within a simple yet basic mathematical model for infection spread, it
      is possible to derive theoretical properties of observations in various
      situations e.g. in "isolation", in households, or during large outbreaks. In each
      case, it is shown that the sampling distribution of observations depends on a
      number of factors, usually not considered in the literature and that must be
      taken into account in order to achieve unbiased inference about the generation
      time distribution. Some implications of these findings for statistical inference
      methods in epidemic spread models are discussed.

PMID- 19854204
TI  - DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling
      between dimerization and ubiquitin binding.
AB  - NEMO is an integral part of the IkappaB kinase complex and serves as a molecular
      switch by which the NF-kappaB signaling pathway can be regulated. Oligomerization
      and polyubiquitin (poly-Ub) binding, mediated through the regulatory CC2-LZ
      domain, were shown to be key features governing NEMO function, but the
      relationship between these two activities remains unclear. In this study, we
      solved the structure of this domain in complex with a designed ankyrin repeat
      protein, which helps its crystallization. We generated several NEMO mutants in
      this domain, including those associated with human diseases incontinentia
      pigmenti and immunodeficiency with or without anhidrotic ectodermal dysplasia.
      Analytical ultracentrifugation and thermal denaturation experiments were used to
      evaluate the dimerization properties of these mutants. A fluorescence-based assay
      was developed, as well, to quantify the interaction to monoubiquitin and poly-Ub
      chains. Moreover, the effect of these mutations was investigated for the full
      length protein. We show that a proper folding of the ubiquitin-binding domain,
      termed NOA/UBAN/NUB, into a stable coiled-coil dimer is required but not
      sufficient for efficient interaction with poly-Ub. In addition, we show that
      binding to poly-Ub and, to a lesser extent, to monoubiquitin increases the
      stability of the NOA coiled-coil dimer. Collectively, these data provide
      structural insights into how several pathological mutations within and outside of
      the CC2-LZ's NOA ubiquitin binding site affect IkappaB kinase activation in the
      NF-kappaB signaling pathway.

PMID- 19854205
TI  - Geometry, thermodynamics, and protein.
AB  - We derive a new continuous free energy formula for protein folding. We obtain the
      formula first by adding hydrophobic effect to a classical free energy formula for
      cavities in water. We then obtain the same formula by geometrically pursuing the
      structure that fits best the well-known global geometric features of native
      structures of globular proteins: 1. high density; 2. small surface area; 3.
      hydrophobic core; 4. forming domains for long polypeptide chains. Conformations
      of a protein are presented as an all atom CPK model P= union or logical
      sum(i=1)(N)B(x(i),r(i)) where each atom is a ball B(x(i),r(i)). All conformations
      satisfy generally defined steric conditions. For each conformation P of a
      globular protein, there is a closed thermodynamic system Omega(P) supersetP
      bounded by the molecular surface M(P). Both methods derive the same free energy
      aV(P)+bA(P)+cW(P), where a,b,c>0, V(P), A(P), and W(P) are volume of Omega(P),
      area of M(P), and area of the hydrophobic surface W(P) subsetM(P), which
      quantifies hydrophobic effect. Minimizing W(P) is sufficient to produce
      statistically significant native like secondary structures and hydrogen bonds in
      the proteins we simulated.

PMID- 19854207
TI  - Non-linear dynamics of the complement system activation.
AB  - The complement system (CS) plays a prominent role in the immune defense. The goal
      of this work is to study the dynamics of activation of the classic and
      alternative CS pathways based on the method of mathematical modeling. The
      principal difficulty that hinders modeling effort is the absence of the measured
      values of kinetic constants of many biochemical reactions forming the CS. To
      surmount this difficulty, an optimization procedure consisting of constrained
      minimization of the total protein consumption by the CS was designed. The
      constraints made use of published data on the in vitro kinetics of elimination of
      the Borrelia burgdorferi bacteria by the CS. Special features of the problem at
      hand called for a significant modification of the general constrained
      optimization procedure to include a mathematical model of the bactericidal effect
      of the CS in the iterative setting. Determination of the unknown kinetic
      constants of biochemical reactions forming the CS led to a fully specified
      mathematical model of the dynamics of cell killing induced by the CS. On the
      basis of the model, effects of the initial concentrations of complements and
      their inhibitors on the bactericidal action of the CS were studied. Proteins
      playing a critical role in the regulation of the bactericidal action of the CS
      were identified. Results obtained in this work serve as an important stepping
      stone for the study of functioning of the CS as a whole as well as for developing
      methods for control of pathogenic processes.

PMID- 19854209
TI  - The application of in vitro technologies to study the metabolism of the
      androgenic/anabolic steroid stanozolol in the equine.
AB  - In this study, the use of equine liver/lung microsomes and S9 tissue fractions
      were used to study the metabolism of the androgenic/anabolic steroid stanozolol
      as an example of the potential of in vitro technologies in sports drug
      surveillance. In vitro incubates were analysed qualitatively alongside urine
      samples originating from in vivo stanozolol administrations using LC-MS on a high
      resolution accurate mass Thermo Orbitrap Discovery instrument, by LC-MS/MS on an
      Applied Biosystems Sciex 5500 Q Trap and by GC-MS/MS on an Agilent 7000A. Using
      high-resolution accurate mass full scan analysis on the Orbitrap, equine liver
      microsome and S9 in vitro fractions were found to generate all the major phase-1
      metabolites observed following in vivo administrations. Additionally, analysis of
      the liver microsomal incubates using a shallower HPLC gradient combined with
      various MS/MS functions on the 5500 Q trap allowed the identification of a number
      of phase 1 metabolites previously unreported in the equine or any other species.
      Comparison between liver and lung S9 metabolism showed that the liver was the
      major site of metabolic activity in the equine. Furthermore, using chemical
      enzyme inhibitors that are known to be selective for particular isoforms in other
      species suggested that an enzyme related to CYP2C8 may be responsible the
      production of 16-hydroxy-stanozolol metabolites in the equine. In summary, the in
      vitro and in vivo phase 1 metabolism results reported herein compare well and
      demonstrate the potential of in vitro studies to compliment the existing in vivo
      paradigm and to benefit animal welfare through a reduction and refinement of
      animal experimentation.

PMID- 19854208
TI  - Methods for genome-wide analysis of DNA methylation in intestinal tumors.
AB  - Recent studies show that colorectal cancer is strongly associated with aberrant
      DNA methylation, which has been linked to the origin and progression of the
      disease. This fact indicates a need for deep analysis of DNA methylation
      alterations during colorectal carcinogenesis. The knowledge obtained from such
      studies will elucidate the mechanisms of epigenetic changes and, through the
      identification and characterization of DNA methylation markers and disease
      specific methylation patterns, will help improve the diagnosis and treatment
      options for patients. The introduction of new methods for genome-wide analysis of
      DNA methylation has been an important step towards achieving these goals. In this
      review, we discuss the role of DNA methylation in intestinal carcinogenesis as
      well as the different methodological approaches that are currently being used for
      methylation analysis on a genome-wide scale.

PMID- 19854210
TI  - The capsule drug device: novel approach for drug delivery to the eye.
AB  - Treatment of age-macular degeneration requires monthly intravitreal injections,
      which are costly and have serious risks. The objective of this study was to
      develop a novel intraocular implant for drug delivery. The capsule drug ring is a
      reservoir inserted in the lens capsule during cataract surgery, refillable and
      capable of delivering multiple drugs. Avastin was the drug of interest in this
      study. Prototypes were manufactured using polymethylmethacrylate sheets as the
      reservoir material, a semi-permeable membrane for controlled delivery and
      silicone check valves for refilling. The device showed near zero-order release
      kinetics and Avastin stability was investigated with accelerated temperature
      studies.

PMID- 19854212
TI  - Contribution of voltage-gated sodium channels to b- and d-waves of frog
      electroretinogram under different conditions of light adaptation.
AB  - The effect of blockade of voltage-gated sodium (Na(v)) channels by tetrodotoxin
      (TTX) on the V-log I function of the ERG b- and d-waves was investigated in light
      and dark adapted frog eyecups. TTX diminished the b- and d-wave amplitude under
      both conditions of adaptation at all stimulus intensities except for the middle
      intensity range in dark adapted eyes, where it had no effect on the b-wave
      amplitude. TTX delayed the time course of the responses, obtained with low
      intensity stimuli and widened the dynamic range of the b-wave. The inhibitory
      effect of TTX on the cone-mediated, but not rod-mediated b- and d-wave amplitude
      persisted after the blockade of proximal retinal activity by NMDA, indicating
      that it may be due to a blockade of Na(v) channels on the ON and OFF bipolar
      cells.

PMID- 19854213
TI  - The neuroendocrinology and neuroscience of energy balance.

PMID- 19854211
TI  - The value of measurement of macular carotenoid pigment optical densities and
      distributions in age-related macular degeneration and other retinal disorders.
AB  - There is increasing recognition that the optical and antioxidant properties of
      the xanthophyll carotenoids lutein and zeaxanthin play an important role in
      maintaining the health and function of the human macula. In this review article,
      we assess the value of non-invasive quantification of macular pigment levels and
      distributions to identify individuals potentially at risk for visual disability
      or catastrophic vision loss from age-related macular degeneration, and we
      consider the strengths and weaknesses of the diverse measurement methods
      currently available.

PMID- 19854214
TI  - The relation of environmental contaminants exposure to behavioral indicators in
      Inuit preschoolers in Arctic Quebec.
AB  - Although lead (Pb) exposure has been identified as an important risk factor in
      child behavioral development, less is known regarding the relation between child
      behavior and exposure to polychlorinated biphenyls (PCBs) and mercury (Hg). Inuit
      children are particularly exposed to these chemicals and the aim of this study
      was to investigate the association between prenatal and postnatal exposure to Pb,
      PCBs, Hg and several aspects of behavioral function in Inuit preschoolers. The
      sample consisted of one hundred and ten 5-year-old Inuit children from Arctic
      Quebec. An umbilical cord blood sample was used to document prenatal exposure to
      Pb, PCBs and Hg. Child blood samples were collected at age 5 and the same
      contaminants were measured. A modified version of the Infant Behavior Rating
      Scale from the Bayley Scales of Infant Development-II was used to assess child
      behavior through examiners' ratings. Furthermore, attention, activity and
      emotional outcomes were assessed through behavioral coding of video recordings
      taken during fine motor testing. Pb exposure during childhood was associated with
      examiners ratings of greater impulsivity, irritability and with coding of
      observed inattention. Prenatal exposure to PCB 153 correlated with the examiners
      ratings of increased state of unhappiness and anxiety during the testing session,
      which was corroborated from video coding since cord PCB 153 was related to fewer
      manifestations of positive affects. No association was found with Hg exposure.
      These data corroborated those from previous Pb cohort studies and revealed an
      association between prenatal PCBs exposure and emotional outcomes in
      preschoolers.

PMID- 19854215
TI  - An MR-compatible device for automated and safe application of laser stimuli in
      experiments employing nociceptive stimulation.
AB  - In this paper the establishment of an automatic laser application device that
      reproducibly delivers laser stimuli in a safe, controlled, and reliable manner is
      presented. Nociceptive stimulation is widely used in functional magnetic
      resonance imaging (fMRI) experiments and a number of different methods are
      employed. One major advantage of laser stimulation as a method to administer
      painful stimuli is that it selectively activates nociceptors. To avoid damage to
      the subject's skin, which might occur if the same skin area were stimulated too
      often, the laser focal spot needs to be repositioned after each stimulus. Here,
      we describe the design of the mechanical set-up, the functionality, the
      computation of laser stimulus intensity, the materials used, the monitoring
      system, and the interface to the control software. Additionally, MR-compatibility
      and functionality of the device were evaluated and assessed in a 3T MR scanner.
      Finally, the reliability and validity of the device were tested and demonstrated.
      It permits easy and investigator-independent use of laser stimulation in the MR
      scanner.

PMID- 19854216
TI  - The effects of immediate and short-term retest on the latencies and amplitudes of
      the auditory event-related potentials in healthy adults.
AB  - OBJECTIVE: To evaluate the immediate and short-term effects of repeated within
      session trials on N1, P2, N2 and P3 latencies and P2, N2 and P3 amplitudes in
      healthy adults. MATERIALS AND METHODS: ERPs were elicited by the auditory oddball
      paradigm and recorded over Fz, Cz and Pz in 18 healthy adults over two sessions,
      one to three days apart, and two within session trials with one to three minutes
      trial-retrial interval. The ERPs' latencies and amplitudes were blindly
      calculated and were analyzed by Analysis of Variance (ANOVA) with repeated
      measures. RESULTS: Significant decreases of N2 amplitude at Fz, P3 amplitude at
      Cz and P3 latency at Pz were recorded in the second-compared to the first within
      session trial (p=0.034, 0.041, 0.046, respectively). There were no significant
      inter-session differences regarding N1, P2, N2 and P3 latencies or amplitudes.
      There was no significant interaction between session and trial. A statistically
      significant difference was found between the first session's mental count errors
      (p=0.039) but there were no significant differences between the second session's
      trials (p=0.581) or between sessions (p=0.328). CONCLUSIONS: N1, P2, N2 and P3
      latencies and amplitudes are stable at short-term intervals of one to three days,
      but one to three minutes' retrial interval may affect P3 latency and N2 and P3
      amplitudes. We suggest that when primary novelty-induced cognitive processes are
      evaluated, single trial sessions or more than three-minute inter-trials interval
      should be employed in order to mitigate habituation.

PMID- 19854217
TI  - Selective up-regulation of CDK2 is critical for TLR9 signaling stimulated
      proliferation of human lung cancer cell.
AB  - Accumulating data suggested that functional TLR9 was expressed in various tumor
      cells and TLR9 signaling could enhance the progression of tumor cells. However,
      the underlying mechanism of TLR9 signaling on the progression of tumors cells
      remains largely undefined. Our previous study demonstrated that the TLR9 agonist
      CpG ODNs could significantly enhance the progression of human lung cancer cells
      in vivo. Here we further evaluated the direct effect of CpG ODNs on the
      proliferation and cell cycle of human lung cancer cells. Our data showed that
      TLR9 agonist CpG ODNs could robustly elevate the proliferation and stimulate cell
      cycle entry of 95D cells in vitro, accompanied by the selectively up-regulated
      expression of CDK2. Furthermore, we found that down-regulation of CDK2 expression
      using siRNA against CDK2 could significantly inhibit the enhanced proliferation
      of 95D cells induced by CpG ODNs. Finally, we investigated that the CpG ODNs
      could selectively enhance the promoter activity of CDK2. Our findings indicated
      that TLR9 signaling could selectively up-regulate the expression of CDK2, which
      was critical for the enhanced proliferation of human lung cancer cells. Our
      results might provide novel insight into the understanding of functional
      expression of TLR9 on the progression of tumor cells.

PMID- 19854218
TI  - CD27 and CCR7 expression on naive T cells, are both necessary?

PMID- 19854219
TI  - Recognition and partial genome characterization by non-specific DNA amplification
      and PCR of a new siadenovirus species in a sample originating from Parus major, a
      great tit.
AB  - A seemingly novel siadenovirus species was detected by PCR and sequencing in the
      sample of a great tit (Parus major) found dead in Hungary. Since the genus
      Siadenovirus has very few known members so far, further study of the virus was
      intriguing not only from epizootiological but also from taxonomical aspects. The
      sample, which had been tested in another PCR survey previously, consisted of less
      than 50 microl of extracted nucleic acid. To ensure sufficient target DNA for an
      extended study, the viral genome had to be preserved. To this end, the sample was
      subjected to a novel method of non-specific DNA amplification. Using the
      amplified DNA as target, different PCR and sequencing strategies were applied
      with consensus or specific primers for the study of the central genome part of
      the putative tit adenovirus. The sequence of supposedly one half (13,628 bp) of
      the genome was determined including eight full genes between the genes of the
      IVa2 and hexon proteins. The gene content of the viral genome fragment as well as
      the results of the phylogenetic analyses with different proteins confirmed the
      discovery of a new species in the genus Siadenovirus. This is the first report on
      the detection of an adenovirus in great tits. The methods, described in this
      work, proved suitable for the recovery of nucleic acid samples that contain
      irreplaceable microbial genomic DNA but are only available in limited quantities.

PMID- 19854220
TI  - Development of a multiplex real-time RT-PCR that allows universal detection of
      influenza A viruses and simultaneous typing of influenza A/H1N1/2009 virus.
AB  - On June 11, 2009, the World Health Organization declared that the influenza
      A/H1N1/2009 virus had become the first influenza pandemic of the 21st century.
      Rapid detection and differentiation from seasonal and avian influenza would be
      beneficial for patient management and infection control. It was the aim of this
      study to develop a real-time RT-PCR that can detect all influenza A viruses and
      offer simultaneous typing for influenza A/H1N1/2009. This would be a useful
      addition to existing diagnostic protocols for influenza A. Its routine use would
      allow laboratories to screen out influenza A/H1N1/2009 positive samples rapidly
      and would reduce overall testing costs.

PMID- 19854221
TI  - Development and clinical evaluation of a microarray for hepatitis C virus
      genotyping.
AB  - The hepatitis C virus (HCV) genotype is the most important factor in predicting
      the outcome of chronic hepatitis C treatment. Therefore, convenient and accurate
      HCV genotyping methods for routine laboratory testing are needed. In this study,
      to identify the HCV genotypes, an oligonucleotide DNA chip was designed using 15
      probes from the 5'-untranslated region. Reverse transcription was combined with
      asymmetric polymerase chain reaction (PCR) to obtain an amplified product for
      hybridization without the need for a denaturation step. In addition, a biotin
      labeled PCR product and streptavidin-Cy3 conjugate were cohybridized
      simultaneously. Clinical sera from Korean and French patients (n=112) were used
      to compare the chip results with those obtained by direct sequencing. The DNA
      chip showed 100% accuracy for the commercial panels and had a lower detection
      limit of 2.8x10(2) IU/ml. Agreement levels between the chip and sequencing
      results at the genotype and subgenotype levels were 100% and 94.6% (106/112),
      respectively. By the combined reverse transcription-asymmetric PCR and
      cohybridization methods, the DNA chip reduced assay time and was convenient to
      use. This DNA chip may be useful for identifying HCV genotypes in clinical
      laboratories.

PMID- 19854222
TI  - Performance of HSV-2 type specific serological tests in men in Kenya.
AB  - This study compared five serological tests with Western blot from University of
      Washington to determine the most accurate method for detecting antibodies to
      herpes simplex virus type 2 (HSV-2) in a male population in Kisumu, Kenya. A
      random sample of 250 fishermen from 18 beaches along Lake Victoria underwent
      serological testing by two generations of the HerpeSelect HSV-2 ELISA ("Focus Gen
      1" and "Focus Gen 2"), Kalon HSV-2 ELISA ("Kalon"), Biokit HSV-2 Rapid Test
      ("Biokit"), and HerpeSelect Express Rapid HSV-2 ("Express") against the Western
      blot test ("WB") as the "gold standard". Sensitivity and specificity of tests in
      this population with a high prevalence of HSV-2 (58% by WB) were: Focus Gen 1:
      98.6% and 63.5%; Focus Gen 2: 99.3% and 52.3%; Biokit: 66% and 90.9%; Express:
      99.3% and 44.3% and Kalon: 98.6% and 85.7%. Increasing the positive cut-off value
      improved the specificity of the Focus Gen 2-84.9% and Kalon to 92.2%. Focus Gen 2
      offered no improvement in specificity over that of Focus Gen 1. Neither rapid
      assay could be recommended as either a stand-alone assay or as a confirmatory
      test. The results of Kalon using a cut-off of 1.5 were the most concordant with
      those of WB for all the approaches tested. However, low positive Kalon test
      results should be interpreted with caution as they could reflect early
      seroconversion or false positive results.

PMID- 19854223
TI  - In vitro infectivity assay for prion titration for application to the evaluation
      of the prion removal capacity of biological products manufacturing processes.
AB  - Prions can be detected and quantified currently by using either immunoassays such
      as Western-blot, ELISA or conformation dependent immunoassay, or an infectivity
      assay in laboratory animals (bioassay). While immunoassays are inexpensive and
      rapid, they are based on the detection of PrP(Sc), the abnormal isoform of the
      prion protein, a surrogate marker for prion infectivity. The bioassay is
      considered the gold-standard analytical method for measuring prion infectivity,
      but it is very costly and time-consuming, involving the destruction of large
      numbers of animals. The use of the transgenic MovS6 cell line is described for
      the development of an in vitro tissue culture infectivity assay (TCIA) for prion
      detection and quantitation. Compared to a bioassay, the TCIA is rapid (
      approximately 8 weeks), easy to implement, much less expensive, and requires far
      fewer animals. After titrating concomitantly a prion-infected brain homogenate
      sample by Western-blot, TCIA and bioassay, data show that the sensitivity of the
      TCIA is close to that of the bioassay, since 1 TCID(50) corresponds to 4 ID(50),
      and 80-fold more sensitive than the Western-blot. The application of the TCIA to
      the evaluation of prion removal in biological products manufacturing processes is
      described using a 15 nm-nanofiltration step of human albumin as a model.

PMID- 19854224
TI  - Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: a
      brief history of stavudine (D4T) and its comparison with other
      dideoxynucleosides.
AB  - The occasion of this 25th anniversary issue encouraged us to reminisce about the
      important history of the discovery of the dideoxynucleoside analogues for the
      treatment of HIV/AIDS and to chronicle our thoughts about a particular exciting
      and rewarding period of our scientific careers. Following the identification of
      the anti-HIV activity of zidovudine (AZT), we participated in the urgent quest to
      discover optimal treatments of HIV infection and AIDS. A number of previously
      synthesized nucleoside analogues were comparatively evaluated, and stavudine
      (D4T) emerged as a promising candidate for development. Following clinical
      evaluation, D4T became a mainstay of the initial antiretroviral combination
      therapy, prolonging and saving numerous lives. It has only recently been
      supplanted by better-tolerated treatments. This article forms part of a special
      issue of Antiviral Research marking the 25th anniversary of antiretroviral drug
      discovery and development, vol. 85, issue 1, 2010.

PMID- 19854225
TI  - Fungal proteins with mannanase activity identified directly from a Congo Red
      stained zymogram by mass spectrometry.
AB  - Secreted fungal proteins with mannanase activity were identified by mass
      spectrometry of bands excised from a Congo Red stained zymogram containing locust
      bean gum as substrate. This technique circumvents the need to locate
      corresponding bands on a parallel gel without substrate and provides good
      accuracy in targeting proteins for identification.

PMID- 19854226
TI  - Experimental methods for studying microbial survival in extraterrestrial
      environments.
AB  - Microorganisms can be used as model systems for studying biological responses to
      extraterrestrial conditions; however, the methods for studying their response are
      extremely challenging. Since the first high altitude microbiological experiment
      in 1935 a large number of facilities have been developed for short- and long-term
      microbial exposure experiments. Examples are the BIOPAN facility, used for short
      term exposure, and the EXPOSE facility aboard the International Space Station,
      used for long-term exposure. Furthermore, simulation facilities have been
      developed to conduct microbiological experiments in the laboratory environment. A
      large number of microorganisms have been used for exposure experiments; these
      include pure cultures and microbial communities. Analyses of these experiments
      have involved both culture-dependent and independent methods. This review
      highlights and discusses the facilities available for microbiology experiments,
      both in space and in simulation environments. A description of the microorganisms
      and the techniques used to analyse survival is included. Finally we discuss the
      implications of microbiological studies for future missions and for space
      applications.

PMID- 19854227
TI  - Adenovirus E1A and E1B-19K proteins protect human hepatoma cells from
      transforming growth factor beta1-induced apoptosis.
AB  - Primary and some transformed hepatocytes undergo apoptosis in response to
      transforming growth factor beta1 (TGFbeta). We report that infection with species
      C human adenovirus conferred resistance to TGFbeta-induced apoptosis in human
      hepatocellular carcinoma cells (Huh-7). Protection against TGFbeta-mediated cell
      death in adenovirus-infected cells correlated with the maintenance of normal
      nuclear morphology, lack of pro-caspases 8 and 3 processing, maintenance of the
      mitochondrial membrane potential, and lack of cellular DNA degradation. The
      TGFbeta pro-apoptotic signaling pathway was blocked upstream of mitochondria in
      adenovirus-infected cells. Both the N-terminal sequences of the E1A proteins and
      the E1B-19K protein were necessary to protect infected cells against TGFbeta
      induced apoptosis.

PMID- 19854228
TI  - Chronic hyperleptinemia induces resistance to acute natriuretic and NO-mimetic
      effects of leptin.
AB  - Apart from controlling energy balance, leptin, secreted by adipose tissue, is
      also involved in the regulation of cardiovascular function. Previous studies have
      demonstrated that acutely administered leptin stimulates natriuresis and vascular
      nitric oxide (NO) production and that these effects are impaired in obese
      animals. However, the mechanism of resistance to leptin is not clear. Because
      obesity is associated with chronically elevated leptin, we examined if long-term
      hyperleptinemia impairs acute effects of leptin on sodium excretion and NO
      production in the absence of obesity. Hyperleptinemia was induced in lean rats by
      administration of exogenous leptin at a dose of 0.5mg/kg/day for 7 days, and then
      acute effect of leptin (1mg/kg i.v.) was studied under general anesthesia. Leptin
      increased fractional sodium excretion and decreased Na(+),K(+)-ATPase activity in
      the renal medulla. In addition, leptin increased the level of NO metabolites and
      cyclic GMP in plasma and aortic wall. These acute effects of leptin were impaired
      in hyperleptinemic animals. In both control and hyperleptinemic groups the effect
      of leptin on Na(+) excretion and renal Na(+),K(+)-ATPase was abolished by
      phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, but not by protein kinase
      B/Akt inhibitor, triciribine,. In contrast, acute effect of leptin on NO
      metabolites and cGMP was abolished by triciribine but not by wortmannin. Leptin
      stimulated Akt phosphorylation at Ser(473) in aortic tissue but not in the
      kidney, and this effect was comparable in control and hyperleptinemic groups.
      These results suggest that hyperleptinemia may mediate "renal" and "vascular"
      leptin resistance observed in obesity.

PMID- 19854229
TI  - Conservation of the egg-laying hormone neuropeptide and attractin pheromone in
      the spotted sea hare, Aplysia dactylomela.
AB  - In the marine opisthobranch mollusc, Aplysia, secreted peptides and proteins play
      an essential role in egg laying and mate attraction. Aplysia californica egg
      laying is initiated by secretion of the egg-laying hormone (ELH) peptide while
      mate attraction is made possible by protein pheromones, such as attractin,
      released into the surrounding seawater with the egg cordon. In this study, we
      investigated the existence of similar egg-laying hormone and attractin products
      in the spotted sea hare, Aplysia dactylomela, a species that is widely
      distributed in almost all tropical and temperate oceans, including Australia's
      Great Barrier Reef. Immunological analysis revealed that an ELH-like transmitter
      is present within bag cell somata and processes of the abdominal ganglion. A
      molecular genetic approach found that the ELH precursor mRNA is synthesized in
      the abdominal ganglia and encodes a 36-residue peptide (dELH) that is cleaved
      from the prohormone prior to secretion. It is most closely related to A.
      californica and A. brasiliana ELH (91.7% identical). We also found that A.
      dactylomela synthesize an attractin pheromone in the albumen gland that is
      released during egg laying. The gene encodes a 58-residue mature protein that is
      74.9% similar to A. californica attractin. We demonstrate that an increase in
      seawater temperature can disrupt attractins higher order interactions, such as
      those with the pheromone temptin, and accelerates attractin degradation.
      Together, these findings further expands our understanding of pheromone
      intermolecular interactions and presents an opportunity for further study of how
      increases in sea water temperature may affect this important marine communication
      system.

PMID- 19854230
TI  - Effects of Endokinin A/B and Endokinin C/D on the modulation of pain in mice.
AB  - Endokinins are novel tachykinins encoded on the human TAC4 and consist of
      Endokinin A (EKA), B (EKB), C (EKC) and D (EKD). To date, the function of
      Endokinins in pain processing was not fully understood. Therefore the aim of this
      study was to investigate the effects of Endokinin A/B (EKA/B, the common C
      terminal decapeptide in EKA and EKB) and Endokinin C/D (EKC/D, the common C
      terminal duodecapeptide in EKC and EKD) on pain modulation at supraspinal level
      in mice. Intracerebroventricular (i.c.v.) administration of EKA/B (1, 3, 12,
      20nmol/mouse) dose dependently induced potent analgesic effect. This effect could
      be fully antagonized by SR140333B but not SR48968C or SR142801. Naloxone could
      also block the analgesic effect, suggesting that this analgesic effect is related
      to opioid receptors. However, i.c.v. administration of EKA/B (10, 30,
      100pmol/mouse) caused hyperalgesic effect significantly, with a "U" shape curve.
      Interestingly, the hyperalgesic effect induced by EKA/B could be attenuated by
      SR140333B, SR142801 but not SR48968C. I.c.v. administration of EKC/D (1, 3, 12,
      20nmol/mouse) also dose dependently induced analgesic effect, which could not be
      blocked by SR48968C or SR142801 or naloxone. But to our astonishment, it could be
      significantly enhanced by SR140333B. More interestingly, the hyperalgesic effect
      induced by EKA/B could be significantly attenuated by EKC/D. In addition, the
      analgesic effect induced by co-administration of EKA/B and EKC/D was much less
      stronger than the effect of either EKA/B or EKC/D.

PMID- 19854231
TI  - Neurokinin-2 receptor antagonism in medial septum influences temporal-order
      memory for objects and forebrain cholinergic activity.
AB  - In the mammalian brain the neurokinin NK(2) receptors are predominantly located
      in the hippocampus, thalamus, septum and frontal cortex. It has been shown that
      administration of the NK(2) receptor agonist, neurokinin A (NKA), into the medial
      septum of rats increases extracellular levels of acetylcholine (ACh) in the
      hippocampus and that NK(2) receptor antagonism blocks this increase. Therefore,
      given the prominent role of hippocampal ACh in information processing, we
      hypothesized that NK(2) receptor antagonism in the medial septum would negatively
      affect learning and memory via its influence on the cholinergic neurons of the
      basal forebrain. We investigated the action of local application of the peptidic
      NK(2) receptor antagonist, Bz-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH (1, 10 and
      100pmol), into the medial septum on object memory for temporal order and spatial
      location using an object novelty paradigm. By means of in vivo microdialysis and
      HPLC analyses, we also examined the influence of NK(2) receptor antagonism in the
      medial septum on ACh in major cholinergic projection areas of the basal
      forebrain, namely, hippocampus, frontal cortex and amygdala. RESULTS: Injection
      of vehicle alone into the medial septum impaired memory for temporal order and
      spatial location of objects. Application of 1pmol of the NK(2) receptor
      antagonist partially reversed this deficit by reinstating memory for temporal
      order. Injection of 10pmol of the NK(2) receptor antagonist into the medial
      septum decreased levels of ACh in the hippocampus (at 30min post-injection), and
      frontal cortex (at 30 and 80min post-injection) in comparison to vehicle.
      However, this apparent decrease was the result of the blockade of a saline
      induced increase in ACh levels.

PMID- 19854232
TI  - Cloning and functional characterization of a new antimicrobial peptide gene StCT1
      from the venom of the scorpion Scorpiops tibetanus.
AB  - Scorpion has an innovative venom gland, which is an important determinant in
      contributing to its successful survival for more than 400 million years. Scorpion
      venom contains a diversity of bioactive peptides, which represent a tremendous
      hitherto unexplored resource for use in drug design and development. Here, StCT1,
      a new antimicrobial peptide gene, was screened and isolated from the venomous
      gland cDNA library of the scorpion Scorpiops tibetanus. The full-length cDNA of
      StCT1 is 369 nucleotides encoding the precursor that contains a putative 24
      residue signal peptide, a presumed 14-residue mature peptide, and an uncommon 37
      residue acidic propeptide at the C-terminus. The minimal inhibitory
      concentrations (MICs) of the synthetic StCT1 peptide against Staphylococcus
      aureus and Micrococcus luteus were 12.5microg/ml and 100microg/ml, respectively.
      The MICs of StCT1 against clinical antibiotics-resistant bacterial strains, were
      50-250microg/ml, 2-40 folds lower than those of penicillin. These results show
      that the antimicrobial peptide encoded by StCT1 gene from the venom of the
      scorpion S. tibetanus is a potential anti-infective polypeptide or lead compound,
      especially for treating antibiotics-resistant pathogens.

PMID- 19854233
TI  - Human astrocytic bradykinin B(2) receptor modulates zymosan-induced cytokine
      expression in 1321N1 cells.
AB  - Bradykinin is an important modulator of the neurons and glial cells of the
      nervous system. Bradykinin secreted from neurons affects astrocytic functions
      such as neurovascular coupling and astrocytic cytokine production. In human
      astrocytes, however, the detailed mechanism of bradykinin-mediated modulation of
      astrocytic functions has not yet been fully elucidated. Here, we report the
      functional expression of the bradykinin B(2) receptor and its modulation of
      zymosan-induced cytokine expression in human astrocytoma 1321N1 cells. Bradykinin
      increased cytosolic [Ca(2+)] in a concentration-dependent manner, whereas [des
      Arg(10)] kallidin (an agonist of the B(1) receptor) did not have this effect.
      Bradykinin also triggered intracellular InsP(3) production. Pretreating the cells
      with HOE140 (icatibant acetate, a B(2) receptor antagonist) inhibited the
      bradykinin-induced increase in cytosolic [Ca(2+)] and InsP(3) production. In
      contrast, [des-Arg(10)]HOE140 (a B(1) receptor antagonist) did not show any
      inhibitory effect. Bradykinin increased the zymosan-induced expression of TNF
      alpha, and interleukin 1beta (IL-1beta) but did not affect the expression of
      interleukin 6 (IL-6) or interleukin 10 (IL-10). Interestingly, a cyclooxygenase-2
      specific inhibitor blocked the bradykinin-induced effect. In contrast to the
      result in human glioma cells, bradykinin inhibits the zymosan-induced expression
      of TNF-alpha and IL-1beta in rat astrocytes, which shows a species-dependent
      manner. These data suggest that bradykinin B(2) receptors are expressed in human
      astrocytoma cells and that they modulate the expression pattern of inflammatory
      cytokines.

PMID- 19854234
TI  - Human health risk assessment of endosulfan. Part III: Occupational handler
      exposure and risk.
AB  - The United States Environmental Protection Agency (USEPA) and the California
      Department of Pesticide Regulation (CDPR) have authority to regulate pesticides,
      respectively, within the United States and within the state of California. Both
      agencies are obligated to protect human and environmental health within the
      geographical boundaries where they have authority. Risk assessment of pesticidal
      active ingredients is conducted by both USEPA and CDPR, yet the agencies have
      different legal mandates that influence how they conduct assessments. Exposure
      estimates are key inputs into the risk assessment. Both agencies released draft
      risk assessments for endosulfan in the same time frame, and while some exposure
      estimates were similar, many differed considerably. This paper focuses on the
      differences in exposure estimates for individuals involved in endosulfan
      applications (handler exposures). Although CDPR and USEPA relied on the same data
      sets for their exposure estimates for most handler scenarios, CDPR estimates were
      in some cases more than an order of magnitude higher than estimates from USEPA.
      Reasons underlying these disparities, and their effects on risk estimates and
      resulting regulatory decisions, are discussed in this paper. Additionally,
      because of differences in legal mandates, CDPR estimated exposures for scenarios
      lacking data, whereas USEPA did not.

PMID- 19854235
TI  - Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in
      rats.
AB  - This study was carried out to evaluate the effect of Moringa oleifera Lam
      (Moringa) seed extract on liver fibrosis. Liver fibrosis was induced by the oral
      administration of 20% carbon tetrachloride (CCl(4)), twice weekly and for 8
      weeks. Simultaneously, M.oleifera Lam seed extract (1g/kg) was orally
      administered daily. The biochemical and histological results showed that Moringa
      reduced liver damage as well as symptoms of liver fibrosis. The administration of
      Moringa seed extract decreased the CCl(4)-induced elevation of serum
      aminotransferase activities and globulin level. The elevations of hepatic
      hydroxyproline content and myeloperoxidase activity were also reduced by Moringa
      treatment. Furthermore, the immunohistochemical study showed that Moringa
      markedly reduced the numbers of smooth muscle alpha-actin-positive cells and the
      accumulation of collagens I and III in liver. Moringa seed extract showed
      significant inhibitory effect on 1,1-diphenyl-2-picrylhydrazyl free radical, as
      well as strong reducing antioxidant power. The activity of superoxide dismutase
      as well as the content of both malondialdehyde and protein carbonyl, which are
      oxidative stress markers, were reversed after treatment with Moringa. Finally,
      these results suggested that Moringa seed extract can act against CCl(4)-induced
      liver injury and fibrosis in rats by a mechanism related to its antioxidant
      properties, anti-inflammatory effect and its ability to attenuate the hepatic
      stellate cells activation.

PMID- 19854236
TI  - Evaluation of the usefulness of biomarkers for cardiac and skeletal myotoxicity
      in rats.
AB  - Since cardiac and skeletal myotoxicity affect the development of drug candidates,
      it is important to detect their toxicity at an early stage of drug development.
      For that purpose, in this study, the usefulness of several cardiac and skeletal
      myotoxic biomarkers in blood were evaluated using two rat models treated
      intraperitoneally with an acetylcholinesterase inhibitor carbofuran (CAF) or a
      synthetic catecholamine isoproterenol (ISO). The biomarkers assayed were fatty
      acid binding protein 3 (Fabp3), myosin light chain 1 (MLC1), cardiac troponin I
      (cTnI), cardiac troponin T (cTnT), aspartate transaminase (AST), lactate
      dehydrogenase (LDH) and creatine kinase (CK). CAF and ISO treatment of rats
      induced greater increases in the levels of Fabp3, MLC1, cTnI and cTnT than in the
      levels of AST, LDH and CK. A kinetic analysis indicated that the levels of all of
      the biomarkers had returned to the basal level by 24h after drug administration.
      Pathological examination revealed lesions in the heart, mainly at the left
      ventricle and septum, in both CAF- and ISO-treated rats. CAF-treated rats showed
      widespread lesions of skeletal muscle that were independent of muscle fiber type,
      while in ISO-treated rats locoregional lesions were observed only in slow twitch
      muscle. Receiver operating characteristic curve analysis of the sensitivity of
      the tested biomarkers indicated that MLC1 and cTnT were the most effective
      biomarkers of cardiotoxicity. For skeletal myotoxicity, Fabp3 and MLC1 were the
      most effective biomarkers based on the specific tissue distribution of these
      proteins. Conversely, the rapid blood clearance of these markers should be taken
      into account when considering the use of these biomarkers.

PMID- 19854237
TI  - Notation-dependent processing of numerical magnitude: electrophysiological
      evidence from Chinese numerals.
AB  - To investigate whether the semantic processing of numbers is notation-dependent
      or notation-independent, three notation stimuli-Arabic digits, Chinese numerals
      written in simple form (Ch-S), and Chinese numerals written in complex form (Ch
      C)-were presented to participants. The participants were asked to judge which
      target numeral (numerical values 1-4 and 6-9) was "smaller or larger than 5"
      while event-related potentials (ERPs) were recorded. Electrophysiological results
      revealed that the voltage activity associated with numerical semantic processing
      was largest across temporo-occipital-parietal electrode sites, regardless of
      input formats. However, the time windows for the semantic processing of numerals
      did not overlap across notations. Furthermore, the main effects of notation and
      notation/distance interaction were still observed at the stage of numerical
      magnitude processing, suggesting that notation might affect the semantic
      processing of numbers. In addition, a right-lateralized N1 for both Arabic digits
      and Ch-C numbers, and a bilateral N1 for Ch-S numbers, were observed; these data
      imply that number processing in Chinese speakers may be different from that in
      Western speakers.

PMID- 19854238
TI  - The variant methylenetetrahydrofolate reductase c.1298A>C (p.E429A) is associated
      with multiple sclerosis in a German case-control study.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of
      the central nervous system. We investigated the association of two missense
      variants of the MTHFR gene, i.e. MTHFR c.677C>T (p.A222V) and c.1298A>C
      (p.E429A), in 138 patients with clinically definite multiple sclerosis of
      relapsing-remitting course and 138 age- and gender-matched healthy controls. No
      significant differences were found in the frequency of the MTHFR c.677C>T
      polymorphism between MS patients and healthy controls. However, the genotype
      frequencies of the missense variant MTHFR c.1298A>C were significantly different
      between patients (AA/AC/CC: 0.34/0.55/0.11) and controls (0.52/0.36/0.12;
      Pearson's chi(2)=11.1; p=0.004). These results suggest that homozygosity for the
      A allele of MTHFR c.1298A>C may be protective against the incidence of MS. If
      confirmed in an independent study sample, the underlying mechanisms should be
      investigated, which may lead to novel insights in biochemical factors influencing
      the aetiology and pathophysiology of MS.

PMID- 19854239
TI  - Caloric restriction alleviates abnormal locomotor activity and dopamine levels in
      the brain of the methionine sulfoxide reductase A knockout mouse.
AB  - Oxidative stress is associated with the aging process, a risk factor for
      neurodegenerative diseases, and decreased by reduced energy intake. Oxidative
      modifications can affect protein function; the sulfur-containing amino acids,
      including methionine, are particularly susceptible to oxidation. A methionine
      sulfoxide can be enzymatically reduced by the methionine sulfoxide reductase
      (Msr) system. Previously, we have shown that MsrA(-/-) mice exhibit altered
      locomotor activity and brain dopamine levels as function of age. Previous studies
      have demonstrated that a caloric restriction enhances antioxidant defense and
      reduces the action of reactive oxygen species. Here we examine locomotor behavior
      and dopamine levels of MsrA(-/-) mice after caloric restriction starting at eight
      months of age and ending at 17 months. The MsrA(-/-) mice did not have any
      significant difference in spontaneous distance traveled when compared to controls
      at 17 months of age. In contrast, our previous report showed decreased locomotor
      activity in the MsrA(-/-) mice at 12 months of age and older when fed ad-libitum.
      After completion of the caloric restriction diet, dopamine levels were comparable
      to control mice. This differs from the abnormal dopamine levels previously
      observed in MsrA(-/-) mice fed ad-libitum. Thus, caloric restriction had a
      neutralization effect on MsrA ablation. In summary, it is suggested that caloric
      restriction alleviates abnormal locomotor activity and dopamine levels in the
      brain of the methionine sulfoxide reductase A knockout mouse.

PMID- 19854240
TI  - gamma-Irradiation induces P2X(7) receptor-dependent ATP release from B16 melanoma
      cells.
AB  - BACKGROUND: Ionizing irradiation causes not only growth arrest and cell death,
      but also release of growth factors or signal transmitters, which promote cancer
      malignancy. Extracellular ATP controls cancer growth through activation of
      purinoceptors. However, there is no report of radiation-induced ATP release from
      cancer cells. Here, we examined gamma-irradiation-induced ATP release and its
      mechanism in B16 melanoma. METHODS: Extracellular ATP was measured by luciferin
      luciferase assay. To investigate mechanism of radiation-induced ATP release, we
      pharmacologically inhibited the ATP release and established stable P2X(7)
      receptor-knockdown B16 melanoma cells using two short hairpin RNAs targeting
      P2X(7) receptor. RESULTS: Cells were exposed to 0.5-8 Gy of gamma-rays.
      Extracellular ATP was increased, peaking at 5 min after 0.5 Gy irradiation. A
      selective P2X(7) receptor channel antagonist, but not anion transporter
      inhibitors, blocked the release of ATP. Further, radiation-induced ATP release
      was significantly decreased in P2X(7) receptor-knockdown cells. Our results
      indicate that gamma-irradiation evokes ATP release from melanoma cells, and
      P2X(7) receptor channel plays a significant role in mediating the ATP release.
      GENERAL SIGNIFICANCE: We suggest that extracellular ATP could be a novel
      intercellular signaling molecule released from cancer cells when cells are
      exposed to ionizing radiation.

PMID- 19854241
TI  - Cathepsin D and apoptosis related proteins are elevated in the brain of autistic
      subjects.
AB  - Autism is a severe neurodevelopmental disorder characterized by problems in
      communication, social skills, and repetitive behavior. Recent studies suggest
      that apoptotic mechanisms may partially contribute to the pathogenesis of this
      disorder. Cathepsin D is the predominant lysosomal protease and is abundantly
      expressed in the brain. It plays an important role in regulation of cellular
      apoptosis and has been shown to mediate apoptosis induced by cytokines tumor
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma. In this study, we
      examined the expression levels of cathepsin D in the autistic brain. We found
      that cathepsin D protein expression was significantly increased in the frontal
      cortex, in pyramidal and granule cells of the hippocampus, and in cerebellar
      neurons in autistic subjects as compared to controls. In addition, we found that
      the expression of the anti-apoptotic protein Bcl-2 was significantly decreased,
      while caspase-3, a critical executioner of apoptosis, was increased in the
      cerebellum of autistic subjects. Previously our studies have shown that Bcl-2
      expression is decreased and the BDNF-Akt-Bcl-2 pathway is compromised in the
      frontal cortex of autistic subjects, which suggested that increased apoptosis may
      be involved in the pathogenesis of autism. Our current finding of decreased Bcl-2
      and increased capase-3 in the cerebellum of autistic subjects further supports
      this suggestion. In addition, the finding of increased cathepsin D in the
      cerebellum of autistic subjects suggests that, through its regulation of
      apoptosis, the altered activities of cathepsin D in the autistic brain may play
      an important role in the pathogenesis of autism.

PMID- 19854242
TI  - The effects of sub-chronic clozapine and haloperidol administration on isolation
      rearing induced changes in frontal cortical N-methyl-D-aspartate and D1 receptor
      binding in rats.
AB  - Glutamate and dopamine disturbances are implicated in frontal cortical
      dysfunction in schizophrenia. Little, however, is known about the nature of
      dopamine D(1) and N-methyl-D-aspartate (NMDA) receptor interactions in the
      illness, nor of the extent of their co-involvement in antipsychotic drug
      response. It is well known that early life adversity may pre-date the development
      of schizophrenia. Using a neurodevelopmental model of schizophrenia, namely post
      weaning social isolation rearing (SIR), we studied the effect of SIR (post natal
      day 21-61) on frontal cortical NMDA and D(1) receptor binding characteristics
      with/without chronic haloperidol (0.1 mg/kg/day i.p.) or clozapine (5 mg/kg/day
      i.p.) treatment, undertaken from post-natal day 50-60. SIR increased frontal
      cortical NMDA-density, with decreased affinity (decreased pK(D)), but reduced
      D(1) receptor density (without effects on pK(D)). In socially reared animals,
      clozapine but not haloperidol increased NMDA receptor density without effects on
      pK(D.) Neither drug markedly affected D(1) receptor density, although clozapine
      increased D(1) affinity. Increased NMDA density in SIR animals was unaffected by
      haloperidol, but further increased by clozapine. However, SIR-associated decrease
      in NMDA affinity remained unaltered despite drug treatment. Reduced D(1) receptor
      density in SIR animals was exacerbated by haloperidol, but unaltered by
      clozapine, without changes in pK(D). SIR thus induces opposing effects on frontal
      cortical NMDA and D(1) radio-receptor binding characteristics, which has direct
      bearing on the mutual interplay of these receptors in schizophrenia. The ability
      of SIR to affect NMDA receptor affinity warrants deeper study. Furthermore, at
      the doses examined, in contrast to haloperidol, clozapine bolsters frontal
      cortical glutamatergic but stabilizes D(1) dopaminergic pathways in a
      neurodevelopmental animal model of schizophrenia, possibly explaining the
      atypical clinical characteristics of this drug.

PMID- 19854243
TI  - Loss of long-term potentiation in the hippocampus after experimental subarachnoid
      hemorrhage in rats.
AB  - Survivors of aneurysmal subarachnoid hemorrhage (SAH) often suffer from cognitive
      impairment such as memory loss. However, the underlying mechanisms of these
      impairments are not known. Long-term potentiation (LTP) of synapses in the
      hippocampus is generally regarded as a molecular substrate of memory. The purpose
      of this study was to examine the effect of SAH on LTP in the hippocampal Schaffer
      collateral (CA3-CA1) pathway in a rat model of SAH. We found SAH caused
      significant vasospasm of the middle cerebral artery (MCA) compared to saline
      injected or sham controls (P<0.001). Basic neurotransmission quantified as
      excitatory post synaptic and spike response from animals with SAH were
      significantly decreased as compared to naive controls (P<0.05). However, sham
      operated and saline injected controls showed similar amplitude as naive controls.
      This suggests that reduction in basic neurotransmission is due to blood in the
      subarachnoid space. Similarly, analysis of LTP demonstrated that naive, sham and
      saline controls have a 92+/-16%, 69+/-27% and 71+/-14% increase over the baseline
      in the average spike amplitude following high frequency stimulation (HFS),
      respectively. This indicates the presence of LTP (P<0.05). In contrast, the spike
      amplitude in animals of SAH returned to baseline level within 60 min post HFS
      indicating the absence of LTP. We conclude that SAH caused vasospasm of the MCA
      that was associated with disrupted basic neurotransmission and plasticity at CA3
      CA1 synapses. These changes might be accountable for the memory loss in humans
      with SAH.

PMID- 19854244
TI  - Pathways from the ventral hippocampus and caudal amygdala to forebrain regions
      that regulate sensorimotor gating in the rat.
AB  - The neural substrates regulating sensorimotor gating in rodents are studied in
      order to understand the basis for gating deficits in clinical disorders such as
      schizophrenia. N-methyl-D-aspartate (NMDA) infusion into the ventral temporal
      lobe, including caudal parts of the ventral hippocampal region and amygdala, has
      been shown to disrupt sensorimotor gating in rats, as measured by prepulse
      inhibition (PPI) of startle. One working model is that reduced PPI after infusion
      of NMDA into this region is mediated via its efferents to ventral forebrain
      structures, i.e. medial prefrontal cortex (mPFC) and nucleus accumbens. Yet, PPI
      disruptive effects persist after lesions of the precommissural fornix, the
      principal output pathway of the hippocampal formation. Here, we aimed to
      characterize non-fornical forebrain projections from this region that might
      mediate the PPI-disruptive effects of the ventral temporal lobe. Electrolytic
      lesions of the precommissural fornix in male Sprague-Dawley rats were followed by
      infusions of fluorogold into the mPFC or by infusions of biotinylated dextan
      amine into the ventral temporal lobe. Projections from the ventral subiculum and
      CA1 regions of the ventral hippocampus to the mPFC and accumbens core and shell
      were interrupted by fornix lesions. Projections to the mPFC and accumbens from
      other regions of the ventral temporal lobe, particularly the lateral entorhinal
      cortex and the embedded olfactory and vomeronasal parts of the caudal amygdala,
      survived fornix lesions. These additional projections coursed rostrally through
      the amygdala and emerged via the stria terminalis, interstitial nuclei of the
      posterior limb of the anterior commissure, and the ventral amygdalofugal pathway.
      PPI-regulatory portions of the ventral temporal lobe innervate the accumbens and
      mPFC via multiple routes. It remains to be determined which of these non-fornical
      projections may be responsible for the persistent regulation of PPI after fornix
      lesions.

PMID- 19854245
TI  - Reactive oxygen species (ROS) in the human neocortex: role of aging and
      cognition.
AB  - Reactive oxygen species (ROS), formed during normal aerobic metabolism, are
      involved in signal transduction and cognitive functions, but highly increased ROS
      concentrations may also have detrimental effects. The aim of the present study
      was to investigate whether aging and cognitive functions are associated with ROS
      generation in human neocortex obtained from neurosurgical patients. ROS formation
      in mitochondria from fresh and re-thawed neocortical specimens was measured by
      monitoring ROS-mediated conversion of dihydrorhodamine 123 to fluorescent
      rhodamine 123. The validity of this technique was characterized in rat brain
      mitochondria. The increase in the concentration-response curve of the complex I
      inhibitor rotenone on ROS generation, as measured by rhodamine 123 (Rh123)
      fluorescence, was much more pronounced than that of rotenone on mitochondrial
      [(3)H]-choline uptake [which indicates changes in the mitochondrial membrane
      potential (DeltaPsi(M))]. Thus, mitochondrial ROS generation can be shown by
      Rh123 fluorescence although this fluorescence may also reflect changes in
      DeltaPsi(M) to some extent. ROS formation in human brain mitochondria positively
      correlated with the age of patients. Moreover, an age-corrected positive
      correlation of ROS formation with presurgical cognitive performance was observed.
      Our data suggest a mild increase in ROS formation with aging possibly reflecting
      a physiological compensation of mitochondrial function. Furthermore, higher
      cognitive performances in tests of executive functions may be paralleled by
      slightly increased ROS levels.

PMID- 19854246
TI  - A genome-wide linkage scan in German shepherd dogs localizes canine platelet
      procoagulant deficiency (Scott syndrome) to canine chromosome 27.
AB  - Scott syndrome is a rare hereditary bleeding disorder associated with an
      inability of stimulated platelets to externalize the negatively charged
      phospholipid, phosphatidylserine (PS). Canine Scott syndrome (CSS) is the only
      naturally occurring animal model of this defect and therefore represents a unique
      tool to discover a disease gene capable of producing this platelet phenotype. We
      undertook platelet function studies and linkage analyses in a pedigree of CSS
      affected German shepherd dogs. Based on residual serum prothrombin and flow
      cytometric assays, CSS segregates as an autosomal recessive trait. An initial
      genome scan, performed by genotyping 48 dogs for 280 microsatellite markers,
      suggested linkage with markers on chromosome 27. Genotypes ultimately obtained
      for a total of 56 dogs at 11 markers on chromosome 27 revealed significant LOD
      scores for 2 markers near the centromere, with multipoint linkage indicating a
      CSS trait locus spanning approximately 14 cm. These results provide the basis for
      fine mapping studies to narrow the disease interval and target the evaluation of
      putative disease genes.

PMID- 19854247
TI  - Proteomic analysis for testis of rats chronically exposed to perfluorododecanoic
      acid.
AB  - Perfluorododecanoic acid (PFDoA), a ubiquitous contaminant detected in
      environmental matrices, wildlife, and human blood, has been shown to produce
      adverse effects on male reproduction in rats. The mechanism of action of PFDoA in
      testis, however, is not well understood. In the present study, male rats were
      orally exposed to PFDoA (0.02, 0.2, and 0.5mg/kg/day for 110 days), and a two
      dimensional gel electrophoresis (2-DE) approach was employed to investigate the
      alteration of protein expression in the testes. Decreased serum progesterone
      levels were observed. Matrix-assisted laser desorption/ionization (MALDI) tandem
      time of flight (TOF/TOF) mass spectrometry analysis allowed the unambiguous
      identification of 40 differentially expressed proteins. These proteins are mainly
      involved in mitochondrial respiration, oxidative stress, sperm activity,
      cytoskeleton and intracellular signal transduction. Furthermore, PFDoA led to
      decreases in activities of superoxide dismutase (SOD), mitochondrial H-ATPase,
      and cytochrome c oxidase as well as to an increase in lipid peroxidation in
      testes. Our results indicated that these proteins, which are involved in
      mitochondrial respiratory and antioxidative responses, play important roles in
      the inhibition of testicular steriodogenesis in response to PFDoA. Our data
      demonstrate that alterations of multiple pathways may be associated with the
      toxic effects of PFDoA on testes. SOD and H-ATPase subunit d may be sensitive to
      PFDoA exposure in testis.

PMID- 19854248
TI  - Accumulation of cadmium in human placenta interacts with the transport of
      micronutrients to the fetus.
AB  - Cadmium (Cd) is a widespread, highly toxic environmental pollutant known to
      accumulate in human placenta. The aim of the present study was to elucidate to
      what extent the accumulation of Cd in human placenta interacts with the transport
      of micronutrients to the fetus. Cd and micronutrients were measured in placenta
      and umbilical cord blood from 44 non-smoking, rural Bangladeshi women, using
      ICPMS. Metallothionein (MT) protein expression was determined in placenta using
      Western blot. Cd in placenta (median 110 microg/kg dry weight, 20 microg/kg wet
      weight) was positively associated with maternal urinary Cd. It was also
      positively associated with Cd in umbilical cord blood (median 0.16 microg/kg),
      but negatively associated with zinc (Zn; median 3mg/kg) in umbilical cord blood.
      Umbilical cord blood Zn was positively associated with birth anthropometry
      measures, and the Cd-related impairment of Zn in umbilical cord blood seemed to
      decrease size at birth. In multivariate analysis, MT protein expression was
      associated with Cd (positively) in placenta, but not with Zn or copper (Cu) in
      placenta. In conclusion, the Cd concentrations in placenta were clearly elevated,
      which seemed to impair Zn transfer to the fetus. Induction of MT explained the
      placental accumulation of Cd, but not the impairment of Zn transport.

PMID- 19854249
TI  - SKH-1 mouse skin painting: a short-term assay to evaluate the tumorigenic
      activity of cigarette smoke condensate.
AB  - The hairless mouse strain SKH-1 was investigated in a short-term assay to assess
      the tumorigenic activity of mainstream cigarette smoke condensate (CSC). The
      design chosen was the two-stage dermal tumorigenicity assay (skin painting), with
      tumor initiation using a single dermal application of the carcinogen/mutagen
      dimethylbenz(a)anthracene applied to the back at a non-tumorigenic dose and tumor
      promotion by repeated dermal applications of CSC at the same site. The mice
      reproducibly developed skin tumors at the application site after 15 weeks at a
      frequency that allowed comparison of the treatment groups. The histopathological
      examination revealed the benign nature of the tumors (keratotic papillomas).
      Prolongation of the application period to 25 weeks resulted in the development of
      malignant tumors (carcinomas), indicating that the benign tumors after 15 weeks
      can be taken as surrogate endpoints for malignancies progressing after further
      treatment. After 15 weeks, tumor incidence (the percentage of tumor-bearing
      mice), tumor multiplicity (the number of tumors per mouse), and tumor-onset (the
      duration of the application period that resulted in a meaningful tumor incidence)
      were positively correlated with the initiating and promoting dose. The
      reproducibility of this assay was at least comparable to that described for other
      skin painting models in the literature. When the assay system was used to compare
      CSCs to which different concentrations of benzo(a)pyrene were added, its ability
      to distinguish these different condensate preparations was comparable to that of
      other models. The results obtained with the SKH-1 mouse strain suggest its
      usefulness in the short-term skin painting assay for the comparative
      investigation of the tumorigenic activity of different CSCs.

PMID- 19854251
TI  - The effects of MAPK inhibitors on a proteasome inhibitor, MG132-induced HeLa cell
      death in relation to reactive oxygen species and glutathione.
AB  - MG132 as a proteasome inhibitor can induce apoptotic cell death through formation
      of reactive oxygen species (ROS). In this study, we investigated the effects of
      MAPK (MEK, JNK or p38) inhibitors on MG132-induced HeLa cell death in relation to
      ROS and glutathione (GSH). MG132-induced cell growth inhibition and apoptosis in
      HeLa cells, which was accompanied by the loss of mitochondrial membrane potential
      (MMP; DeltaPsi(m)). MG132 increased ROS level including O(2)(*-) and GSH depleted
      cell number in HeLa cells. All the MAPK inhibitors slightly enhanced the cell
      growth inhibition but did not intensify apoptosis in MG132-treated HeLa cells.
      Each MAPK inhibitor differentially changed the levels of ROS and GSH content in
      MG132-treated cells. In conclusion, MAPK inhibitors partially influence
      apoptosis, ROS and GSH levels in MG132-treated HeLa cells.

PMID- 19854250
TI  - Investigation of the role of the thiazolidinedione ring of troglitazone in
      inducing hepatotoxicity.
AB  - Troglitazone (TGZ) is an orally active hypoglycemic agent which is used for the
      treatment of non-insulin-dependent diabetes mellitus. It had been associated with
      severe drug-induced liver failure which resulted in its withdrawal from the
      market in 2000. While the exact mechanism of its toxicity remains unknown, it has
      been postulated that the formation of toxic reactive metabolites (RMs) may play
      an important role in the hepatotoxicity of TGZ. The purpose of this study is to
      investigate the role of sulfur moiety of thiazolidinedione (TZD) nucleus in
      inducing liver toxicity via the formation of RMs. An analogue of TGZ,
      trosuccinimide (TSN), was synthesized chemically where the sulfur moiety of
      thiazolidinedione ring was replaced by a methylene group. Both compounds were
      incubated independently with human liver microsomes enriched with glutathione
      (GSH) and normal human hepatocytes (THLE-2 cell lines) to profile GSH-adducts
      using ultra performance liquid chromatography tandem mass spectrometry
      (UPLC/MS/MS). Four RM-GSH conjugates of TGZ were identified during the profiling
      experiments of which three were related to the sulfur moiety of the TZD ring,
      whereas no RM of TSN was detected in both microsomes and hepatocytes. MTT, GSH
      and protein carbonyl (PC) assays were performed using THLE-2 hepatocytes to
      measure the levels of toxicity of TGZ and TSN in vitro. Finally, peroxisome
      proliferator activated receptor gamma (PPAR(gamma)) binding activity was measured
      to check the binding affinities of both TGZ and TSN. The calculated binding
      affinities of TGZ and TSN were 332.2 and 1106.0 microM, respectively. Our results
      indicated collectively that TSN (EC(50)=138.5+/-7.32 microM) was less toxic than
      TGZ (EC(50)=27.2+/-4.8 microM) in THLE-2 hepatocytes. As both compounds were
      shown to bind to PPAR(gamma), the substitution of the TZD moiety may be
      beneficial from a drug design perspective. In conclusion, our study confirmed
      that the TZD ring of TGZ may be partially responsible for its liver toxicity in
      humans via the formation of RMs.

PMID- 19854252
TI  - Novel pMDI formulations for pulmonary delivery of proteins.
AB  - In this paper, we demonstrate that co-spray-drying a model protein with sodium
      carboxymethylcellulose (NaCMC) protects protein integrity during spray-drying,
      and that the resultant spray-dried powders can be successfully dispersed in
      hydrofluoroalkane (HFA) propellant to prepare pressurised metered dose (pMDI)
      formulations that exhibit high respirable fractions. The spray-dried powders were
      formulated as HFA-134a pMDI suspensions in the absence of any other excipients
      (e.g. surfactants) or co-solvents (e.g. ethanol). The in vitro aerosolisation
      profile of these systems was assessed using the twin stage impinger; fine
      particle fractions (FPF) > or = 50% of the recovered dose were obtained.
      Following storage for five months, the aerosolisation performance was reassessed;
      the NaCMC-free formulation demonstrated a significant decrease in FPF, whereas
      the performance of the NaCMC-modified formulations was statistically equivalent
      to their initial performance. Thus, formulation of pMDI suspensions using NaCMC
      based spray-dried powders is a promising approach for the pulmonary delivery of
      proteins and peptides.

PMID- 19854253
TI  - Enhancement of nasal and intestinal calcitonin delivery by the novel Pheroid
      fatty acid based delivery system, and by N-trimethyl chitosan chloride.
AB  - Therapeutic peptides are highly potent and specific in their functions, but
      difficulties in their administration require parallel development of viable
      delivery systems to improve their bioavailability. In this study the potential of
      a novel lipid-based colloidal delivery system for improving the absorption of
      nasally and intestinally administered salmon calcitonin (sCT) was investigated.
      Two types of delivery vehicles based on Pheroid technology was prepared and
      characterized. Liposome-like bilayer vesicles had a mean diameter of 1.0 microm
      and microsponges were 1.6 microm. Doses of 10 IU/kg and 500 IU/kg bodyweight sCT
      were administered intranasally and intestinally to rats, respectively. The
      obtained absorption enhancement with Pheroid vesicles and Pheroid microsponges
      were also compared with the absorption enhancement obtained with N-trimethyl
      chitosan chloride (TMC). With the inclusion of 0.5% (w/v) TMC the maximum plasma
      concentration (C(max)) of sCT increased from 72.6+/-6.1 pg/ml to 478.5+/-6.1
      pg/ml after nasal administration. Pheroid vesicles and Pheroid microsponges
      increased the C(max) values of sCT to 262.64+/-17.1 pg/ml and 202.66+/-28.6
      pg/ml, respectively. The time to reach the maximum concentration (T(max)) was
      also significantly decreased from 35 min to approximately 14 min. Intestinal
      administration of Pheroid formulations increased the C(max) of sCT from 249.1+/
      21.5 pg/ml to 386.2+/-45.5 and 432.1+/-18.9 pg/ml, respectively for Pheroid
      vesicles and Pheroid microsponges. TMC increased the C(max) of sCT to 738.9+/
      277.1 pg/ml. TMC and Pheroid technology could offer the potential to
      significantly improve intranasal and intestinal absorption of sCT and reduce the
      variability in absorption.

PMID- 19854254
TI  - Preparation and evaluation of carboplatin biodegradable polymeric nanoparticles.
AB  - The present study was designed to evaluate targeting efficiency of carboplatin
      anticancer drug. Drug was encapsulated in natural biodegradable polymer sodium
      alginate. The nanoparticles were prepared by the ion gelification technique and
      evaluated for encapsulation efficiency, loading capacity, in vitro release
      pattern and targeting efficiency. Drug encapsulation efficiency was about 52.24
      68.70% for different formulations. In vitro release profile showed duration of
      drug release was also increased (more than 12 h) by nanoparticulate formulation
      as compared to pure drug (up to 3 h). The formulations were parenterally
      administered to laca mice and the drug was detected in body organs like liver,
      lungs and spleen. In case of free drug, less amount of drug was found in liver,
      lungs and spleen as compared to drug encapsulated nanoparticles. Thus sodium
      alginate nanoparticles can be used for targeting carboplatin and it can be a
      promising tool in the delivery of anticancer drugs.

PMID- 19854256
TI  - Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in
      streptozotocin-induced-diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cucumis trigonus Roxb. (Cucurbitaceae) fruit is
      used in the Indian traditional medicine for the treatment of diabetes. Based on a
      number of reports on the blood glucose level reduction and the other
      complications of diabetes associated with some Cucurbitaceae plants, the
      antidiabetic effect of Cucumis trigonus fruit was investigated. AIM OF THE STUDY:
      To investigate the antidiabetic action of the aqueous extract of Cucumis trigonus
      fruits in the different models of rats. MATERIALS AND METHODS: The antidiabetic
      activity of aqueous extract of Cucumis trigonus fruit was evaluated by using
      normal and streptozotocin-induced-diabetic rats. The acute effect of aqueous
      extract was evaluated by administering 500 mg/kg p.o. to normoglycemic rats. In
      the chronic model, the aqueous extract was administered to normal and STZ-induced
      diabetic rats at dose of 500 mg/kg p.o. per day for 21 days. Blood glucose levels
      and body weights were monitored at specific intervals and different biochemical
      parameters were also carried out. RESULTS: The statistical data indicated the
      significant increase in the body weight, liver glycogen and serum insulin level
      and decrease in the blood glucose, glycosylated hemoglobin levels, total
      cholesterol and serum triglycerides. HDL cholesterol level was significantly
      increased when treated with the extract. CONCLUSION: The aqueous fruit extract of
      Cucumis trigonus has had beneficial effects in reducing the elevated blood
      glucose level and lipid profile of STZ-induced-diabetic rats.

PMID- 19854257
TI  - Ultrastructural alterations of the tegument of Raillietina echinobothrida treated
      with the stem bark of Acacia oxyphylla (Leguminosae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Acacia oxyphylla Graham ex
      Bentham is used as an anthelmintic by the natives of Mizoram (North-East India).
      AIM OF THE STUDY: The present study was performed to evaluate whether or not the
      plant-derived components caused any ultrastructural changes in the tegumental
      interface of the parasite. MATERIALS AND METHODS: The test parasite Raillietina
      echinobothrida, the cestode of domestic fowl, was exposed to the ethanolic crude
      extract and acetone fraction of stem bark of Acacia oxyphylla for varying
      concentrations and time duration and processed for transmission electron
      microscopy as soon as paralysis set in the treated parasites. RESULTS: Treatment
      with crude alcoholic extract and its acetone fraction revealed complete
      inactivation and flaccid paralysis of the cestode, which was soon followed by
      death. The treated parasites also exhibited intense vacuolization of the
      tegumental layers along with complete disorganization and/or erosion of
      microtriches. CONCLUSIONS: Considerable structural alterations in the treated
      parasites are suggestive of an efficient vermicidal activity of the Acacia
      oxyphylla stem bark-derived botanicals against cestodes.

PMID- 19854255
TI  - Age-related loss of spiral ganglion neurons.
AB  - Spiral ganglion neurons (SGNs) are the relay station for auditory information
      between hair cells and central nervous system. Age-related decline of auditory
      function due to SGN loss can not be ameliorated by hearing aids or cochlear
      implants. Recent findings clearly indicate that survival of SGNs during aging
      depends on genetic and environmental interactions, which can be demonstrated at
      the systemic, tissue, cellular, and molecular levels. At the systemic level, both
      insulin/insulin-like growth factor-1 and lipophilic/steroid hormone pathways
      influence SGN survival during aging. At the level of organ of the Corti, it is
      difficult to determine whether age-related SGN loss is primary or secondary
      degeneration. However, a late stage of SGN degeneration may be independent of age
      related loss of hair cells. At the cellular and molecular level, several
      pathways, particularly free radical and calcium signaling pathways, can influence
      age-related SGN loss, and further studies should determine how these pathways
      contribute to SGN loss, such as whether they directly or indirectly act on SGNs.
      With the advancement of recent genetic and pharmacologic tools, we should not
      only understand how SGNs die during aging, but also find ways to delay this loss.

PMID- 19854258
TI  - Evaluation of the diuretic and analgesic activities of the rhizomes of Rumex
      abyssinicus Jacq in mice.
AB  - AIM OF THE STUDY: Rumex abyssinicus Jacq (Polygonaceae) has been used
      traditionally for treatment of hypertension, inflammatory and painful conditions
      in Ethiopia. The present study aimed to evaluate the diuretic and analgesic
      activities of extracts of Rumex abyssinicus at different doses in mice. MATERIALS
      AND METHODS: The effect on urine volume and urinary electrolyte (Na(+), K(+) and
      Cl(-)) was assessed for a period of 5h following oral administration of aqueous
      (500 mg/kg, 750 mg/kg or 1000 mg/kg) or 80% methanolic (250 mg/kg, 500 mg/kg or
      750 mg/kg) extract or furosemide (10mg/kg). Acetic acid-induced writhing and hot
      plate tests were employed to study the analgesic effect of 80% methanolic
      extracts (250 mg/kg, 500 mg/kg or 1000 mg/kg, P.O.) and compared with that of
      aspirin (100mg/kg, P.O.) or morphine (10mg/kg, sc). RESULTS: The extracts
      displayed dose-dependent diuretic and analgesic effects. The highest doses of
      both extracts markedly and significantly increased (P<0.001) urine volume and
      urinary electrolytes, qualitatively similar to that of furosemide. 1000 mg/kg of
      the extract reduced the number of writhing by 67.6% (P<0.001) and conferred more
      than 70% protection against thermally induced pain stimuli after 45 min of
      treatment comparable to that of aspirin and morphine, respectively. CONCLUSION:
      These findings collectively indicate that the extracts exhibited significant
      diuretic and analgesic activities, providing evidence, at least in part, for its
      folkloric use.

PMID- 19854259
TI  - Serum and muscle interleukin-15 levels decrease in aging mice: correlation with
      declines in soluble interleukin-15 receptor alpha expression.
AB  - Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine with favorable
      effects on muscle mass and body composition. Modulation of IL-15 levels has been
      suggested as a treatment for sarcopenia and age-associated increases in
      adiposity. However, it is unclear whether IL-15 levels change during aging, as
      measurement of IL-15 at physiological concentrations in mice has been technically
      difficult, and translational regulation of IL-15 is complex. Moreover, the IL-15
      receptor alpha (IL-15Ralpha) can comprise part of a membrane-associated receptor
      complex, or appear as a soluble form which stabilizes IL-15 and facilitates IL-15
      secretion. Here, we report measurement of physiological levels of murine IL-15,
      and determine that muscle and serum IL-15 levels decline progressively with age.
      However, expression of IL-15 mRNA and membrane-associated subunits of the IL-15
      receptor did not change with age in muscle. Expression of soluble IL-15Ralpha
      (sIL-15Ralpha) mRNA declined 5-fold with age, and serum IL-15 levels correlated
      highly with muscle sIL-15 mRNA expression, suggesting declines in sIL-15Ralpha
      expression lead to decreased circulating IL-15 levels during aging. These
      findings complement studies which described several single-nucleotide
      polymorphisms in the human IL-15Ralpha gene which impact muscularity and
      adiposity, and provide a technical basis for further investigation of IL-15 and
      the sIL-15Ralpha in determining body composition in aging mice, as a model for
      humans.

PMID- 19854260
TI  - Regulatory role of monoamine neurotransmitters in astrocytic NT-3 synthesis.
AB  - Astrocytes actively control neuronal activity and synaptic transmission and by
      producing various neurotrophic factors represent an important local cellular
      source of trophic support in the normal and diseased brain. Our present study
      showed the ability of astrocytes to synthesize neurotrophin-3 (NT-3) and the
      active involvement of the monoamine neurotransmitters noradrenaline, adrenaline,
      dopamine, and serotonin, as well as basic intracellular second messenger systems,
      in the regulation of NT-3 production in neonatal rat cortical astrocytes. Using a
      new NT-3 specific enzyme-immunoassay, we showed that neonatal rat cortical and,
      for comparison, cerebellar astrocytes in primary culture can synthesize NT-3; the
      basal cellular content of NT-3 protein was 23.2+/-0.4 pg NT-3/mg cell protein and
      23.6+/-0.9 pg NT-3/mg cell protein, respectively. The examined neurotransmitters,
      with the exception of serotonin, were able to potently and transiently increase
      NT-3 mRNA and NT-3 protein content; their maximal effects were dose- and time
      dependent. Noradrenaline (1 microM), adrenaline (1 microM), and dopamine (100
      microM) showed a maximal increase in NT-3 cellular content after 6h treatment
      causing a 1.9-, 1.8- and 2.7-fold elevation, respectively. Prior to the observed
      increase in NT-3 protein levels, the examined catecholamines increased NT-3 mRNA
      levels with maximal effects observed after 1h (noradrenaline) and 2h (adrenaline
      and dopamine) of incubation causing 2.4-, 2.6- and 3-fold elevation,
      respectively. Screening different activators of basic intracellular second
      messenger systems for their influence on NT-3 synthesis revealed that forskolin
      (20 microM), dibutyryl cAMP (dBcAMP) (100 microM), as well as calcimycin (1
      microM) (Ca(2+) ionophore A23187) and phorbol 12-myristate 13-acetate (TPA) (100
      nM), markedly increased the cellular level of NT-3 protein. Neurotransmitter
      induced NT-3 levels were susceptible (to varying degrees) to inhibition by H-89
      (protein kinase A inhibitor) or staurosporin (protein kinase C inhibitor), which
      led us to conclude that downstream signaling responsible for the stimulation of
      NT-3 synthesis by monoamines in astrocytes consists of multiple, complex
      intracellular mechanisms involving the cAMP/protein kinase A pathway, activation
      of protein kinase C, as well as mobilization of Ca(2+) ions. Our results indicate
      for the first time that monoaminergic neurotransmitters play an important role in
      the regulation of NT-3 synthesis in cultured rat astrocytes.

PMID- 19854261
TI  - Effects of dinuclear copper(II) complexes with 6-(benzylamino)purine derivatives
      on AhR and PXR dependent expression of cytochromes P450 CYP1A2 and CYP3A4 genes
      in primary cultures of human hepatocytes.
AB  - A series of dinuclear copper(II) complexes of the compositions [Cu(2)(micro
      L(n))(2)(micro-Cl)(2)Cl(2)] (1, 2), [Cu(2)(micro-L(n))(4)Cl(2)]Cl(2).2H(2)O (3,
      4) and [Cu(2)(micro-L(n))(4)(ClO(4))(2)](ClO(4))(2).xSolv (5, 6; xSolv=4MeOH for
      5 and 2EtOH for 6), involving 6-(benzylamino)purine derivatives (L(n)), have been
      evaluated with the aim to determine their possible drug interactions and their
      capability to induce the expression of major drug-metabolizing cytochromes P450.
      The above-mentioned complexes have been chosen based on the fact that substantial
      both in vitro (cytotoxicity, SOD-mimic) and in vivo (antidiabetic) biological
      activity has been found for them. As models, primary cultures of human
      hepatocytes and human hepatoma cells HepG2 transiently transfected with a plasmid
      containing dioxin-responsive element fused to the luciferase reporter gene (DRE
      LUC) have been chosen. It has been found that the tested complexes 1-6 did not
      significantly induce the expression of CYP1A2 and CYP3A4 mRNAs in the
      concentration range of 0.1-10.0microM, in three different primary human
      hepatocyte cultures after 24h of the treatment. On the other hand, the model
      inducers, i.e. 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and rifampicin,
      significantly increased the levels of CYP1A2 and CYP3A4 mRNAs in all cultures. In
      addition, compounds 1-6 did not transactivate DRE-LUC in transiently transfected
      HepG2, while TCDD strongly induced luciferase activity after 24h of incubation.
      Based on the obtained results, it may be concluded that the studied dinuclear
      copper(II) complexes 1-6 possess very low toxicological potential to cause drug
      interactions in terms of transcriptional activation of the major human
      cytochromes P450.

PMID- 19854262
TI  - Alteration of serotonin transporter messenger RNA level in the peripheral blood
      mononuclear cells from simian/human immunodeficiency virus infected Chinese
      rhesus macaques (Macaca mulatta).
AB  - Serotonin transporter (SERT, 5-HTT) is a key element in the serotonergic system
      which is probably involved in the psychiatric disorders commonly observed in
      people living with HIV/AIDS. However, no information is available about the
      effects of HIV infection on SERT expression. In this study, a TaqMan real-time RT
      PCR method was established, levels of SERT mRNA in the peripheral blood
      mononuclear cells (PBMCs) and various tissues from normal Chinese rhesus
      macaques, in PBMCs from 32 SHIV-sf162p4 infected rhesus macaques and from 8
      rhesus macaques before and 7, 14, 21, 28 and 196 days after SHIV-sf162p4
      infection, and in PBMCs before and after in vitro phytohemagglutinin (PHA)
      stimulation were examined. It was found that SERT mRNA was widely distributed in
      lymphoid tissues; the level of SERT mRNA was significantly reduced in PBMCs from
      SHIV infected rhesus macaques and in PBMCs stimulated with PHA. The most evident
      decrease (to about one-tenth) in SERT mRNA level was observed at day 7 after SHIV
      infection. Difference in PBMC SERT mRNA level between 5-HTTLPR genotypes was not
      statistically significant. These data indicated that, in addition to previously
      observed abnormality in serotonin metabolism, SERT expression might be affected
      in HIV/AIDS, which might be associated with depression and other psychiatric
      disorders in HIV/AIDS. Besides, this study provided a basis for quantitative
      analysis of SERT gene expression under effects of host and environmental factors,
      such as 5-HTTLPR genotypes, SERT targeting drugs or other infectious agents.

PMID- 19854264
TI  - Antioxidants rescue photoreceptors in rd1 mice: Relationship with thiol
      metabolism.
AB  - We have previously shown that the use of a combination of antioxidants delayed
      the degeneration process in rd1 mouse retina. In an effort to understand the
      mechanism of action of these substances (zeaxanthin, lutein, alpha-lipoic acid,
      glutathione, and Lycium barbarum extract) the changes in the levels of several
      proteins and oxidative stress markers in the rd1 retina have been studied. The
      treatment increased glutathione peroxidase activity and glutathione levels and
      decreased cystine concentrations in rd1 retinas. Considering all the results
      obtained from treated and untreated animals, a high correlation was present
      between glutathione concentration and glutathione peroxidase activity, and there
      was a negative correlation between glutathione retinal concentration and number
      of TUNEL-positive cells. No difference was observed between the numbers of nNOS-
      and NADPH-diaphorase-positive cells in treated and untreated rd1 mice. Thiol
      contents and thiol-dependent peroxide metabolism seem to be directly related to
      the survival of photoreceptors in rd1 mouse retina.

PMID- 19854263
TI  - PKC-delta controls the fMLF-induced overproduction of superoxide by neutrophils.
AB  - Antimicrobial defense by neutrophils implicates the production of reactive oxygen
      species. Neutrophil responses can be modulated by agonists such as bacterial
      peptides and proinflammatory factors that modulate neutrophil activity and
      survival. We evaluated the production of superoxide anions (O(2)(-)) in response
      to fMLF by normal human neutrophils after 3 days of preincubation with GM-CSF +
      IL-4 + TNF-alpha (survival medium). After 3 days of incubation in survival
      medium, long-lived neutrophils produced up to six times more O(2)(-) relative to
      control neutrophils in response to fMLF and WKYMVM. This augmented response to
      fMLF was preferentially linked to formyl peptide receptor (FPR), whereas the
      response to WKYMVM was dependent on formyl peptide receptor-like 1 (FPRL-1). Real
      time RT-PCR revealed a diminution of FPR and FPRL-1 expression in neutrophils
      incubated in survival medium. fMLF-induced overproduction of O(2)(-) by long
      lived neutrophils was independent of intracellular calcium mobilization. The
      protein tyrosine phosphorylation profile of long-lived neutrophils was modified
      with respect to control cells. Pharmacological inhibitors of intracellular
      signals indicated that mechanisms of the excessive fMLF-induced production of
      O(2)(-) by long-lived neutrophils implicated the protein kinase C (PKC) pathway,
      preferentially the PKC-delta isoform, whose protein was augmented in these cells.
      Thus, long-term cytokine exposure modifies molecular pathways and functional
      characteristics of the neutrophil.

PMID- 19854265
TI  - Puerarin attenuates high-glucose-and diabetes-induced vascular smooth muscle cell
      proliferation by blocking PKCbeta2/Rac1-dependent signaling.
AB  - Oxidative stress has been implicated in several steps leading to the development
      of diabetic vascular complications. The purpose of this study was to determine
      the efficacy and the possible mechanism of puerarin on high-glucose (HG; 25 mM)
      induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and
      neointimal formation in a carotid arterial balloon injury model of obese Zucker
      rats. Our data demonstrated that puerarin significantly inhibited rat VSMC
      proliferation as well as reactive oxygen species (ROS) generation and NADPH
      oxidase activity induced by HG treatment. Further studies revealed that HG
      treatment resulted in phosphorylation and membrane translocation of PKCbeta2 as
      well as Rac1, p47phox, and p67phox subunits, leading to NADPH oxidase activation.
      Puerarin treatment remarkably disrupted the phosphorylation and membrane
      translocation of PKCbeta2 as well as Rac1, p47phox, and p67phox subunits.
      Blocking PKCbeta2 by infection with AdDNPKCbeta2 also abolished HG-induced
      phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits
      as well as ROS production and NADPH oxidase activation in VSMCs. In vivo
      neointimal formation of obese Zucker rats evoked by balloon injury was evidently
      attenuated by the administration of puerarin. These results demonstrate that
      puerarin may exert inhibitory effects on HG-induced VSMC proliferation via
      interfering with PKCbeta2/Rac1-dependent ROS pathways, thus resulting in the
      attenuation of neointimal formation in the context of hyperglycemia in diabetes
      mellitus.

PMID- 19854266
TI  - Consequences of long-term oral administration of the mitochondria-targeted
      antioxidant MitoQ to wild-type mice.
AB  - The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies
      of pathologies in vivo and is being developed as a therapy for humans. However,
      it is unclear whether the protective action of MitoQ is entirely due to its
      antioxidant properties, because long-term MitoQ administration may alter whole
      body metabolism and gene expression. To address this point, we administered high
      levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks and
      investigated the effects on whole-body physiology, metabolism, and gene
      expression, finding no measurable deleterious effects. In addition, because
      antioxidants can act as pro-oxidants under certain conditions in vitro, we
      examined the effects of MitoQ administration on markers of oxidative damage.
      There were no changes in the expression of mitochondrial or antioxidant genes as
      assessed by DNA microarray analysis. There were also no increases in oxidative
      damage to mitochondrial protein, DNA, or cardiolipin, and the activities of
      mitochondrial enzymes were unchanged. Therefore, MitoQ does not act as a pro
      oxidant in vivo. These findings indicate that mitochondria-targeted antioxidants
      can be safely administered long-term to wild-type mice.

PMID- 19854268
TI  - Isoprostanes in fetal and neonatal health and disease.
AB  - Isoprostanes are prostaglandin-like bioactive molecules generated via
      nonenzymatic peroxidation of lipid membrane-derived arachidonic acid by free
      radicals and reactive oxygen species. Their cognate receptors, biological
      actions, and signaling pathways are poorly understood. Aside from being sensitive
      and specific biomarkers of oxidative stress, E- and F-ring isoprostanes have
      important biological functions and likely mediate many of the disease-related
      pathological changes for which they are used as indicators. The biochemical
      pathways involved in isoprostane formation, their pathogenetic relevance to adult
      disease states, and their biological function are addressed. Developmentally,
      plasma and tissue content data show that isoprostane levels are highest during
      fetal and early neonatal life, when compared with adults. As such, the available
      data suggesting that isoprostanes play an important biological role, as well as
      possibly actively participate in the regulation of pulmonary vascular tone and
      the transition from fetal to postnatal life, are here reviewed. Lastly, the
      association between isoprostanes and certain neonatal clinical conditions is
      addressed. Although its existence has been recognized for almost 20 years, little
      is known about the critical importance of isoprostanes during fetal life and
      immediate neonatal period. This review is an attempt to bridge this knowledge
      gap.

PMID- 19854267
TI  - In vivo oxidative stress in brain of Alzheimer disease transgenic mice:
      Requirement for methionine 35 in amyloid beta-peptide of APP.
AB  - Numerous studies have demonstrated oxidative damage in the central nervous system
      in subjects with Alzheimer disease and in animal models of this dementing
      disorder. In this study, we show that transgenic mice modeling Alzheimer disease
      PDAPP mice with Swedish and Indiana mutations in the human amyloid precursor
      protein (APP)-develop oxidative damage in brain, including elevated levels of
      protein oxidation (indexed by protein carbonyls and 3-nitrotyrosine) and lipid
      peroxidation (indexed by protein-bound 4-hydroxy-2-nonenal). This oxidative
      damage requires the presence of a single methionine residue at position 35 of the
      amyloid beta-peptide (Abeta), because all indices of oxidative damage in brain
      were completely prevented in genetically and age-matched PDAPP mice with an M631L
      mutation in APP. No significant differences in the levels of APP, Abeta(1-42),
      and Abeta(1-40) or in the ratio Abeta(1-42)/Abeta(1-40) were found, suggesting
      that the loss of oxidative stress in vivo in the brain of PDAPP(M631L) mice
      results solely from the mutation of the Met35 residue to Leu in the Abeta
      peptide. However, a marked reduction in Abeta-immunoreactive plaques was observed
      in the M631L mice, which instead displayed small punctate areas of nonplaque
      immunoreactivity and a microglial response. In contrast to the requirement for
      Met at residue 35 of the Abeta sequence (M631 of APP) for oxidative damage,
      indices of spatial learning and memory were not significantly improved by the
      M631L substitution. Furthermore, a genetically matched line with a different
      mutation-PDAPP(D664A)-showed the reverse: no reduction in oxidative damage but
      marked improvement in memory. This is the first in vivo study to demonstrate the
      requirement for Abeta residue Met35 for oxidative stress in the brain of a
      mammalian model of Alzheimer disease. However, in this specific transgenic mouse
      model of AD, oxidative stress is neither required nor sufficient for memory
      abnormalities.

PMID- 19854269
TI  - Sonic hedgehog is involved in formation of the ventral optic cup by limiting Bmp4
      expression to the dorsal domain.
AB  - Accumulating evidence suggests that Sonic hedgehog (Shh) signaling plays a
      crucial role in eye vesicle patterning in vertebrates. Shh promotes expression of
      Pax2 in the optic stalk and represses expression of Pax6 in the optic cup. Shh
      signaling contributes to establishment of both proximal-distal and dorsal-ventral
      axes by activating Vax1, Vax2, and Pax2. In the dorsal part of the developing
      retina, Bmp4 is expressed and antagonizes the ventralizing effects of Shh
      signaling through the activation of Tbx5 expression in chick and Xenopus. To
      examine the roles of Shh signaling in optic cup formation and optic stalk
      development, we utilized the Smoothened (Smo) conditional knockout (CKO) mouse
      line. Smo is a membrane protein which mediates Shh signaling into inside of
      cells. Cre expression was driven by Fgf15 enhancer. The ventral evagination of
      the optic cup deteriorated from E10 in the Smo-CKO, whereas the dorsal optic cup
      and optic stalk develop normally until E11. We analyzed expression of various
      genes such as Pax family (Pax2/Pax6), Vax family (Vax1/Vax2) and Bmp4. Bmp4
      expression was greatly upregulated in the optic vesicle by the 21-somite stage.
      Then Vax1/2 expression was decreased at the 20- to 24-somite stages. Pax2/6
      expression was affected at the 27- to 32-somite stages. Our data suggest that the
      effects of the absence of Shh signaling on Vax1/Vax2 are mediated through
      increased Bmp4 expression throughout the optic cup. Also unchanged patterns of
      Raldh2 and Raldh3 suggest that retinoic acid is not the downstream to Shh
      signaling to control the ventral optic cup morphology.

PMID- 19854270
TI  - Pharmacology of EAPB0203, a novel imidazo[1,2-a]quinoxaline derivative with anti
      tumoral activity on melanoma.
AB  - In spite of the development of new anticancer drugs by the pharmaceutical
      industry, melanoma and T lymphomas are diseases for which medical advances remain
      limited. Thus, there was an urgent need of new therapeutics with an original
      mechanism of action. Since several years, our group develops quinoxalinic
      compounds. In this paper, the first preclinical results concerning one lead
      compound, EAPB0203, are presented. This compound exhibits in vitro cytotoxic
      activity on A375 and M4Be human melanoma cell lines superior to that of imiquimod
      and fotemustine. A liquid chromatography-mass spectrometry method was first
      validated to simultaneously quantify EAPB0203 and its metabolite, EAPB0202, in
      rat plasma. Thereafter, the pharmacokinetic profiles of EAPB0203 were studied in
      rat after intravenous and intraperitoneal administrations. After intraperitoneal
      administration the absolute bioavailability remains limited (22.7%). In
      xenografted mouse, after intraperitoneal administration of 5 and 20mg/kg,
      EAPB0203 is more potent than fotemustine. The survival time was increased up to 4
      and 2 weeks compared to control mice and mice treated by fotemustine,
      respectively. The results of this study demonstrate the relationship between the
      dose of EAPB0203 and its effects on tumor growth. Thus, promising efficacy,
      tolerance and pharmacokinetic data of EAPB0203 encourage the development towards
      patient benefit.

PMID- 19854271
TI  - Computational discovery of novel trypanosomicidal drug-like chemicals by using
      bond-based non-stochastic and stochastic quadratic maps and linear discriminant
      analysis.
AB  - Herein we present results of a quantitative structure-activity relationship
      (QSAR) studies to classify and design, in a rational way, new antitrypanosomal
      compounds by using non-stochastic and stochastic bond-based quadratic indices. A
      data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297
      having other clinical uses, is used to develop QSAR models based on linear
      discriminant analysis (LDA). Non-stochastic model correctly classifies more than
      93% and 95% of chemicals in both training and external prediction groups,
      respectively. On the other hand, the stochastic model shows an accuracy of about
      the 87% for both series. As an experiment of virtual lead generation, the present
      approach is finally satisfactorily applied to the virtual evaluation of 9 already
      synthesized in house compounds. The in vitro antitrypanosomal activity of this
      series against epimastigote forms of Trypanosoma cruzi is assayed. The model is
      able to predict correctly the behaviour for the majority of these compounds. Four
      compounds (FER16, FER32, FER33 and FER 132) showed more than 70% of epimastigote
      inhibition at a concentration of 100 microg/mL (86.74%, 78.12%, 88.85% and
      72.10%, respectively) and two of these chemicals, FER16 (78.22% of AE) and FER33
      (81.31% of AE), also showed good activity at a concentration of 10 microg/mL. At
      the same concentration, compound FER16 showed lower value of cytotoxicity
      (15.44%), and compound FER33 showed very low value of 1.37%. Taking into account
      all these results, we can say that these three compounds can be optimized in
      forthcoming works, but we consider that compound FER33 is the best candidate.
      Even though none of them resulted more active than Nifurtimox, the current
      results constitute a step forward in the search for efficient ways to discover
      new lead antitrypanosomals.

PMID- 19854272
TI  - Thermally sensitive gels based on chitosan derivatives for the treatment of oral
      mucositis.
AB  - The aim of the present work was the development of a thermally sensitive
      mucoadhesive gel based on chitosan derivatives for the treatment of oral
      mucositis. Trimethyl chitosan (TMC) and methylpyrrolidinone chitosan (MPC) were
      considered. They were mixed with glycerophosphate (GP) according to different
      polymer/GP molar ratios and characterized for gelation properties by means of
      rheological analysis in comparison with chitosan. The influence of molecular
      weight and substitution degree (SD) of TMC on gelation temperature and time was
      investigated. The mucoadhesive properties of the mixtures were also assessed
      using porcine buccal mucosa. The best properties were shown by TMC with high MW
      and low SD mixed with GP according to 1:2molar ratio. Such mixture was loaded
      with benzydamine hydrochloride, an anti-inflammatory drug with antimicrobial
      properties and subjected to in vitro drug release and wash away test. The
      formulation based on TMC/GP mixture was able to prolong drug release and to
      withstand the removal physiological mechanisms. The antimicrobial properties of
      both vehicle and formulation were investigated. Also in absence of drug, TMC/GP
      mixture was characterized by antimicrobial properties.

PMID- 19854273
TI  - Direct evidence of the cyclooxygenase pathway of prostaglandin synthesis in
      arthropods: genetic and biochemical characterization of two crustacean
      cyclooxygenases.
AB  - Prostaglandins, well-known lipid mediators in vertebrate animals, have also shown
      to play certain regulatory roles in insects and other arthropods acting on
      reproduction, immune system and ion transport. However, knowledge of their
      biosynthetic pathways in arthropods is lacking. In the present study, we report
      the cloning and expression of cyclooxygenase (COX) from amphipod crustaceans
      Gammarus spp and Caprella spp. The amphipod COX proteins contain key residues
      shown to be important for cyclooxygenase and peroxidase activities. Differently
      from all other known cyclooxygenases the N-terminal signal sequence of amphipod
      enzymes is not cleaved during protein expression in mammalian cells. The C
      terminus of amphipod COX is shorter than that of mammalian isoforms and lacks the
      KDEL(STEL)-type endoplasmic reticulum retention/retrieval signal. Despite that,
      amphipod COX proteins are N-glycosylated and locate similarly to the vertebrate
      COX on the endoplasmic reticulum and nuclear envelope. Both amphipod COX mRNAs
      encode functional cyclooxygenases that catalyze the transformation of arachidonic
      acid into prostaglandins. Using bioinformatic analysis we identified a COX-like
      gene from the human body louse Pediculus humanus corporis genome that encodes a
      protein with about 30% sequence identity with human COX-1 and COX-2. Although the
      COX gene is known to be absent from genomes of Drosophila sp., Aedes aegypti,
      Bombyx mori, and other insects, our studies establish the existence of the COX
      gene in certain lineages within the insect world.

PMID- 19854274
TI  - Crystal structure and statistical coupling analysis of highly glycosylated
      peroxidase from royal palm tree (Roystonea regia).
AB  - Royal palm tree peroxidase (RPTP) is a very stable enzyme in regards to acidity,
      temperature, H(2)O(2), and organic solvents. Thus, RPTP is a promising candidate
      for developing H(2)O(2)-sensitive biosensors for diverse applications in industry
      and analytical chemistry. RPTP belongs to the family of class III secretory plant
      peroxidases, which include horseradish peroxidase isozyme C, soybean and peanut
      peroxidases. Here we report the X-ray structure of native RPTP isolated from
      royal palm tree (Roystonea regia) refined to a resolution of 1.85A. RPTP has the
      same overall folding pattern of the plant peroxidase superfamily, and it contains
      one heme group and two calcium-binding sites in similar locations. The three
      dimensional structure of RPTP was solved for a hydroperoxide complex state, and
      it revealed a bound 2-(N-morpholino) ethanesulfonic acid molecule (MES)
      positioned at a putative substrate-binding secondary site. Nine N-glycosylation
      sites are clearly defined in the RPTP electron-density maps, revealing for the
      first time conformations of the glycan chains of this highly glycosylated enzyme.
      Furthermore, statistical coupling analysis (SCA) of the plant peroxidase
      superfamily was performed. This sequence-based method identified a set of
      evolutionarily conserved sites that mapped to regions surrounding the heme
      prosthetic group. The SCA matrix also predicted a set of energetically coupled
      residues that are involved in the maintenance of the structural folding of plant
      peroxidases. The combination of crystallographic data and SCA analysis provides
      information about the key structural elements that could contribute to explaining
      the unique stability of RPTP.

PMID- 19854275
TI  - Automatic identification and clustering of chromosome phenotypes in a genome wide
      RNAi screen by time-lapse imaging.
AB  - High-throughput time-lapse microscopy is an excellent way of studying gene
      function by collecting time-resolved image data of the cellular responses to gene
      perturbations. With the increase in both data amount and complexity,
      computational methods capable of dealing with large image data sets are required.
      While image processing methods have been successfully applied to endpoint assays
      in the past, the analysis of complex time-resolved read-outs was so far still too
      immature to be applied on a large-scale. Here, we present a complete
      computational processing pipeline for such screens. By automatic image processing
      and machine learning, a quantitative description of phenotypic dynamics is
      obtained from the raw bitmaps. In order to visualize the resulting phenotypes in
      their temporal context, we introduce Event Order Maps allowing a concise
      representation of the major tendencies of causes and consequences of phenotypic
      classes. In order to cluster the phenotypic kinetics, we propose a novel
      technique based on trajectory representation of multidimensional time series. We
      demonstrate the use of these methods applying them on a genome wide RNAi screen
      by time-lapse microscopy.

PMID- 19854276
TI  - Identification of genes differentially expressed in hemocytes of Scylla
      paramamosain in response to lipopolysaccharide.
AB  - Although the crab Scylla paramamosain has been cultured in China for a long time,
      little knowledge is available on how crabs respond to infection by bacteria. A
      forward suppression subtractive hybridization (SSH) cDNA library was constructed
      from their hemocytes and the up-regulated genes were identified in order to
      isolate differentially expressed genes in S. paramamosain in response to
      bacterial lipopolysaccharide (LPS). A total of 721 clones on the middle scale in
      the SSH library were sequenced. Among these genes, 271 potentially functional
      genes were recognized based on the BLAST searches in NCBI and were categorized
      into seven groups in association with different biological processes using AmiGO
      against the Gene Ontology database. Of the 271 genes, 269 translatable DNA
      sequences were predicted to be proteins, and the putative amino acid sequences
      were searched for conserved domains and proteins using the CD-Search service and
      BLASTp. Among 271 genes, 179 (66.1%) were annotated to be involved in different
      biological processes, while 92 genes (33.9%) were classified as an unknown
      function gene group. It was noted that only 18 of the 271 genes (6.6%) had
      previously been reported in other crustaceans and most of the screened genes
      showed less similarity to known sequences based on BLASTn results, suggesting
      that 253 genes were found for the first time in S. paramamosain. Furthermore, two
      up-regulated genes screened from the SSH library were selected for full-length
      cDNA sequence cloning and in vivo expression study, including Sp-superoxide
      dismutase (Sp-Cu-ZnSOD) gene and Sp-serpin gene. The differential expression
      pattern of the two genes during the time course of LPS challenge was analyzed
      using real-time PCR. We found that both genes were significantly expressed in LPS
      challenged crabs in comparison with control. Taken together, the study primarily
      provides the data of the up-regulated genes associated with different biological
      processes in S. paramamosain in response to LPS, by which the interesting genes
      or proteins potentially involved in the innate immune defense of S. paramamosain
      will be investigated in future.

PMID- 19854277
TI  - A long form of shrimp astakine transcript: molecular cloning, characterization
      and functional elucidation in promoting hematopoiesis.
AB  - Hemocytes play important roles in crustacean immune responses. Generation of new
      hemocytes (hematopoiesis) is thus necessary to maintain homeostasis which is
      vital to crustaceans. In vertebrates, certain cytokines have been demonstrated to
      regulate hematopoiesis and immune responses. In invertebrates, however, little is
      known about cytokines related to hematopoiesis. In the present study, we cloned
      an astakine molecule from hemocytic cDNA of tiger shrimp (Penaeus monodon) which
      was 1509 bp in length with a 5'-UTR of 143 bp, a coding region of 375 bp and a 3'
      UTR of 991 bp. The present clone (GenBank accession no. EU980444) showed to be a
      longer form of astakine transcript with an extra insert of 671 bp in the 3'-UTR
      than the NCBI-recorded shrimp astakine cDNA sequence (GenBank accession no.
      AY787657). The deduced protein had 124 amino acid residues, including a signal
      peptide and one prokineticin domain. The calculated molecular weight (MW) of the
      mature peptide was 11,295 Da and pI was 5.2. Phylogenetically, this molecule is
      most similar to astakine-related molecules of arthropod including tiger shrimp
      astakine, crayfish astakines 1, 2a and 2b, aphid astakine-like molecule and
      parasitic wasp astakine-like molecule. Nested RT-PCR showed that astakine mRNA is
      expressed in many tissues and organs of the shrimp such as eyestalk, subcuticular
      epithelium, gills, heart, hepatopancreas, lymphoid organ, intestine, muscle,
      nerve and hemocytes. Real-time PCR further revealed that astakine mRNA is
      expressed mainly in the hemocytes. The astakine transcript is not inducible in
      the hemocytes until 24 h post LPS injection of shrimp. The recombinant protein of
      shrimp astakine (rPmAst) was synthesized using insect cell-baculovirus expression
      system. The authenticity of rPmAst protein was examined by MALDI-MS/MS
      spectrometry. Using ESI-MS it was determined that the MW of C-terminally
      histidine-tagged recombinant protein is 12,107 Da. It is 10 Da less than the
      computer-predicted MW (12,117 Da), allowing the formation of five pairs of
      disulfide bonds. Using BrdU incorporation assay it was demonstrated that the
      injection of rPmAst to the shrimp promoted cell proliferation in hematopoietic
      tissues. Therefore, we conclude that shrimp astakine functions as a cytokine that
      influences cell proliferation in the hematopoietic tissues.

PMID- 19854278
TI  - Caffeine increases the linearity of the visual BOLD response.
AB  - Although the blood oxygenation level dependent (BOLD) signal used in most
      functional magnetic resonance imaging (fMRI) studies has been shown to exhibit
      nonlinear characteristics, most analyses assume that the BOLD signal responds in
      a linear fashion to stimulus. This assumption of linearity can lead to errors in
      the estimation of the BOLD response, especially for rapid event-related fMRI
      studies. In this study, we used a rapid event-related design and Volterra kernel
      analysis to assess the effect of a 200 mg oral dose of caffeine on the linearity
      of the visual BOLD response. The caffeine dose significantly (p<0.02) increased
      the linearity of the BOLD response in a sample of 11 healthy volunteers studied
      on a 3 T MRI system. In addition, the agreement between nonlinear and linear
      estimates of the hemodynamic response function was significantly increased
      (p=0.013) with the caffeine dose. These findings indicate that differences in
      caffeine usage should be considered as a potential source of bias in the analysis
      of rapid event-related fMRI studies.

PMID- 19854279
TI  - Musical and verbal semantic memory: two distinct neural networks?
AB  - Semantic memory has been investigated in numerous neuroimaging and clinical
      studies, most of which have used verbal or visual, but only very seldom, musical
      material. Clinical studies have suggested that there is a relative neural
      independence between verbal and musical semantic memory. In the present study,
      "musical semantic memory" is defined as memory for "well-known" melodies without
      any knowledge of the spatial or temporal circumstances of learning, while "verbal
      semantic memory" corresponds to general knowledge about concepts, again without
      any knowledge of the spatial or temporal circumstances of learning. Our aim was
      to compare the neural substrates of musical and verbal semantic memory by
      administering the same type of task in each modality. We used high-resolution PET
      H(2)O(15) to observe 11 young subjects performing two main tasks: (1) a musical
      semantic memory task, where the subjects heard the first part of familiar
      melodies and had to decide whether the second part they heard matched the first,
      and (2) a verbal semantic memory task with the same design, but where the
      material consisted of well-known expressions or proverbs. The musical semantic
      memory condition activated the superior temporal area and inferior and middle
      frontal areas in the left hemisphere and the inferior frontal area in the right
      hemisphere. The verbal semantic memory condition activated the middle temporal
      region in the left hemisphere and the cerebellum in the right hemisphere. We
      found that the verbal and musical semantic processes activated a common network
      extending throughout the left temporal neocortex. In addition, there was a
      material-dependent topographical preference within this network, with
      predominantly anterior activation during musical tasks and predominantly
      posterior activation during semantic verbal tasks.

PMID- 19854280
TI  - Improved characterization of BOLD responses for evoked sensory stimuli.
AB  - Pain and somatosensory processing involves an interaction of multiple neuronal
      networks. One result of these complex interactions is the presence of
      differential responses across brain regions that may be incompletely modeled by a
      straightforward application of standard general linear model (GLM) approaches
      based solely on the applied stimulus. We examined temporal blood oxygenation
      level dependent (BOLD) signatures elicited by two stimulation paradigms (brush
      and heat) providing innocuous and noxious stimuli. Data were acquired from 32
      healthy male subjects (2 independent cohorts). Regional time courses and model
      free analyses of the first cohort revealed distinct temporal features of the BOLD
      responses elicited during noxious versus innocuous stimulation. Specifically, a
      biphasic (dual peak) BOLD signal was observed in response to heat but much less
      so in response to brush stimuli. This signal was characterized by a stimulus
      locked response along with a second peak delayed by approximately 12.5 s. A cross
      validation error analysis determined a modified design matrix comprising two
      explanatory variables (EVs) as a parsimonious means to model the biphasic
      responses within a GLM framework. One EV was directly derived from the
      stimulation paradigm (EV1), while the second EV (EV2) was EV1 shifted by 12.5 s.
      The 2EV GLM analysis enabled a more detailed characterization of the elicited
      BOLD responses, particularly during pain processing. This was confirmed by
      application of the model to a second, independent cohort[AU1]. Furthermore, the
      delayed component of the biphasic response was strongly associated with the
      noxious heat stimuli, suggesting that this may represent a sensitive fMRI link of
      pain processing.

PMID- 19854281
TI  - Somatosensory cortical activation identified by functional MRI in preterm and
      term infants.
AB  - Functional MRI (fMRI) has not previously been used systematically to investigate
      brain function in preterm infants. We here describe statistically robust and
      reproducible fMRI results in this challenging subject group using a programmable
      somatosensory stimulus synchronized with MR image acquisition which induced well
      localized positive blood oxygen level dependent (BOLD) responses contralateral to
      the side of the stimulation in: 11 preterm infants (median post menstrual age 33
      weeks and 4 days, range 29+1 to 35+3); 6 control infants born at term gestational
      age; and 18 infants born preterm (median gestational age at birth 30 weeks and 5
      days, range 25+4 to 36+0) but studied at term corrected gestational age.
      Bilateral signals were identified in 8 of the ex-preterm infants at term age.
      Anatomical confirmation of appropriate activations was provided with diffusion
      tensor imaging (DTI) based tractography which identified connecting pathways from
      the regions of activation through the ipsilateral corticospinal tracts and
      posterior limb of the internal capsule. These results demonstrate that it is
      possible to reliably identify positive BOLD signals in the infant brain and that
      fMRI techniques can also be applied in the study of preterm infants.

PMID- 19854282
TI  - Calculation of glomerular filtration rate in conscious rats by the use of a bolus
      injection of iodixanol and a single blood sample.
AB  - INTRODUCTION: To establish a simple and convenient procedure for the
      determination of glomerular filtration rate (GFR) in conscious rats, we developed
      a single-blood-sample method, in contrast to the conventional three-sample
      method, using a bolus injection of the nonionic contrast medium iodixanol.
      METHODS: Iodixanol was intravenously administered at 1500 mg I/kg to healthy or
      renal-impaired rats, and blood was collected 60, 120, and 180 min later. Serum
      iodixanol concentrations were measured by HPLC, and serum urea nitrogen (UN) and
      creatinine concentrations were determined as renal function tests. RESULTS: In
      rats subjected to 1/2 and 3/4 nephrectomies, GFR values decreased significantly
      without and with increases in serum UN and creatinine concentrations,
      respectively. In rats treated subcutaneously with gentamicin sulfate (GM) at 80
      mg/kg/day or puromycin aminonucleoside (PAN) at 15 mg/kg/day for 10 consecutive
      days, the GFR values decreased or showed a tendency to decrease before increases
      in serum UN and creatinine concentrations. Accordingly, when the GFR decreased to
      more than 60% of the basal value, serum UN or creatinine concentrations became
      elevated. The GFR values obtained from the three-sample method were closely
      correlated (r=0.83) with those calculated from the estimated distribution volume
      (V) and serum iodixanol concentration 120 min after iodixanol injection in the
      single-blood-sample method in which serum iodixanol concentrations ranged between
      20 and 250 microg I/mL. DISCUSSION: These results suggest that the single-blood
      sample method with a bolus injection of iodixanol, allowing for the repeated use
      of the same animals, is an expedient procedure without ensuring accurate urine
      collection.

PMID- 19854283
TI  - A novel neuropsychological assessment to discriminate between ischemic and
      nonischemic dementia.
AB  - INTRODUCTION: In the present study we have elaborated a multivariate-multifactor
      diagnostic method for diagnosis of ischemic and nonischemic dementia, and
      validated it using different human populations. Our purpose was to improve
      dementia diagnosis by means of comprehensive neuropsychological assessment and
      the control of intervening variables. METHODS: Data were obtained from 114
      healthy volunteers to 101 patients consecutively referred for suspected dementia.
      On the basis of neuromorphological criteria, the patient sample was subdivided
      into those with ischemic lesions (IL: N=12) and without ischemic lesions (non-IL:
      N=89). The patient groups and the healthy subjects (HS) were matched according to
      age, education, sex ratio and handedness. A comprehensive neuropsychological
      battery was administered to all the participants. RESULTS: The two patient groups
      differed in their Hachinski ischemic score, but not in terms of demographic
      variables, the Blessed rating scale, Mini Mental State, Geriatric Depression
      Scale, or other measures. Discriminant analysis selected fifteen
      neuropsychological variables from the comprehensive battery, and these were found
      to provide accuracy of classification in 98% of HS and 87% of the patients
      considered as a whole. Considering the three groups, those variables provided
      accuracy of classification in 98% of HS, 82% of IL patients and 82% of non-IL
      patients. Subtests were internally consistent (Cronbach's alpha: 0.87) and a
      positive association between ischemic lesions and cognitive impairment was
      observed when the 15 dependent variables were added. DISCUSSION: It is possible
      to select a combination of cognitive tests that discriminated HS from dementia
      patients and, within this category, patients with and without ischemic lesions.
      Analysis of the 15 variables provides an improved method for diagnosis of
      ischemic vs. nonischemic lesion dementia in humans.

PMID- 19854284
TI  - Intestinal microflora functions in laboratory mice claimed to harbor a "normal"
      intestinal microflora. Is the SPF concept running out of date?
AB  - For many years, laboratory animal breeders have used a mixture of eight bacterial
      strains, the so-called Altered Schaedler Flora (ASF) to inoculate Caesarian
      derived offspring when establishing colonies of Specific Pathogen Free (SPF)
      rodents fulfilling the criteria worked out by regulatory agencies as AALAS,
      FELASA, etc. However, recently it was shown in this journal that such SPF animals
      harbored a fecal flora far different from that of feral mice. Over the years, we
      have worked with functional aspects of host-microbe interactions(s) and the aim
      of the present study was to analyze some intestinal microbial biochemical
      activities in mice harboring an ASF flora. In the five parameter studied, the ASF
      mice showed a pattern similar to what is found in germfree mice and rats,
      demonstrating an absence of microorganisms capable of performing these reactions.
      These findings call for a re-considering of the SPF concept. Presence of
      important microbiological functions should be taken into consideration when
      rodents are used in biomedical research.

PMID- 19854285
TI  - The therapeutic efficacy of erdosteine in the treatment of chronic obstructive
      bronchitis: a meta-analysis of individual patient data.
AB  - Erdosteine, a drug approved for the treatment of acute and chronic pulmonary
      diseases, has been shown to be an effective treatment for chronic bronchitis or
      COPD (CB/COPD) in several studies, although marked differences in the perception
      of its usefulness still remain. AIM: to test the available evidence for the
      efficacy of erdosteine in adults with stable or exacerbated CB/COPD. METHODS:
      Meta-analysis of individual patient data from both published and unpublished
      randomized controlled trials (RCTs) comparing erdosteine with placebo/mucolytics,
      given for up to 10 days in association with standard therapy (RCTs used for
      regulatory drug approval). Individual patient data were provided by the
      manufacturer of erdosteine, Edmond Pharma (Milano, Italy). Endpoints were symptom
      scores (cough frequency and intensity, sputum viscosity and purulence, difficulty
      to expectorate, catarrh rhonchi at auscultation, dyspnoea), a cumulative global
      efficacy index (cGEI), and an overall physician efficacy assessment (OA).
      RESULTS: individual data from 1046 patients from 15 RCTs (12 on exacerbated and 3
      on stable CB/COPD) were obtained. Erdosteine induced a significant reduction of
      cGEI vs comparators (-1.02; 95% CI: from -1.60 to -0.44; p=0.0006), both placebo
      and mucolytics. On individual symptoms, it positively impacted on cough frequency
      (-0.19; 95% CI: from -0.34 to -0.03) and intensity (-0.30; 95% CI: from -0.44 to 
      0.17), sputum viscosity (-0.28; 95% CI: from -0.49 to -0.07), difficulty to
      expectorate (-0.24; 95% CI: from -0.40 to -0.08), and catarrh ronchi at
      auscultation (-0.35; 95% CI: from -0.60 to -0.10). The effects on dyspnoea were
      only significant vs placebo, whereas sputum purulence was not significantly
      modified. The OA also favoured erdosteine, doubling the chance of success
      compared with placebo and mucolytics: OR (odds ratio) 2.06; (95% CI: from 1.27 to
      3.33). The treatment with erdosteine was well tolerated. Adverse events, mainly
      gastrointestinal, were reported by 10.2% of patients compared to 11.0% in the
      reference groups. CONCLUSIONS: Treatment with erdosteine is associated with a
      significant benefit in terms of symptom amelioration both vs placebo and
      mucolytics in patients with CB/COPD. Although with some limitations (e.g. not
      fully validated scores) this review reinforces the use of erdosteine, in
      combination with standard therapy, in respiratory diseases characterized by
      increased expectoration, namely acute CB/COPD exacerbations.

PMID- 19854286
TI  - Brood predation pressure during parental care does not influence parental enzyme
      activities related to swimming activity in a teleost fish.
AB  - Predation is considered one of the main costs to reproduction but is rarely
      examined from a physiological perspective. In particular, little is known about
      the influence of brood predation pressure on the physiology of parents engaged in
      care. Brood defense, even when there is no direct threat to the parent, can be
      costly as it requires constant vigilance and chasing predators to protect the
      developing brood and maintain parental investment (i.e., fitness). Our goal was
      to examine the influence of natural variation in nest predation pressure on the
      physiology of the teleost smallmouth bass Micropterus dolomieu, an animal that
      provides sole-paternal care for developing offspring. More specifically, we used
      indicators of anaerobic (lactate dehydrogenase [LDH]) and aerobic capacity
      (cytochrome c oxidase [CCO] and citrate synthase [CS]) in axial white muscle and
      pectoral red muscle to test for differences in antipredator performance of nest
      guarding males across six lakes with natural variation in nest predation
      pressure. Pectoral red muscle enzyme activities and protein concentrations were
      highly conserved among populations, while axial white muscle showed differences
      in LDH activities, CCO activities and protein concentrations. However, there was
      no evidence for higher metabolic capacities in fish from lakes with increased
      brood predation pressure. Clearly, factors other than predation pressure have a
      greater influence on white muscle metabolic capacities. Additional research is
      needed to clarify the extent to which biotic and abiotic factors influence the
      enzyme activity and organismal performance in wild animals, particularly at the
      level of the individual and population.

PMID- 19854287
TI  - Feast to famine: The effects of food quality and quantity on the gut structure
      and function of a detritivorous catfish (Teleostei: Loricariidae).
AB  - The gastrointestinal (GI) tract and associated organs are some of the most
      metabolically active tissues in an animal. Hence, when facing food shortages or
      poor food quality, an animal may reduce the size and function of their GI tract
      to conserve energy. We investigated the effects of prolonged starvation and
      varying food quality on the structure and function of the GI tract in a
      detritivorous catfish, Pterygoplichthys disjunctivus, native to the Amazonian
      basin, which experiences seasonal variation in food availability. After 150 days
      of starvation or consumption of a wood-diet too low in quality to meet their
      energetic needs, the fish reduced the surface area of their intestines by 70 and
      78%, respectively, and reduced the microvilli surface area by 52 and 27%,
      respectively, in comparison to wild-caught fish consuming their natural diet and
      those raised in the laboratory on a high-quality algal diet. Intake and dietary
      quality did not affect the patterns of digestive enzyme activity along the guts
      of the fish, and the fish on the low-quality diet had similar mass-specific
      digestive enzyme activities to wild-caught fish, but lower summed activity when
      considering the mass of the gut. Overall, P. disjunctivus can endure prolonged
      starvation and low food quality by down-regulating the size of its GI tract.

PMID- 19854288
TI  - The effect of peptide absorption on PepT1 gene expression and digestive system
      hormones in rainbow trout (Oncorhynchus mykiss).
AB  - The present study evaluates the effect of protein source (dipeptides, free amino
      acids, and intact protein) on development and growth of Salmonid fish alevin.
      Specifically, we follow the expression of oligopeptide transporter protein PepT1
      in the intestine of rainbow trout (Oncorhynchus mykiss). Fish were fed
      exogenously one of four diets: three formulated (lysyl-glycine dipeptide
      supplemented diet - PP, free lysine and glycine supplemented diet - AA, control
      diet with no lysine - CON) or commercial starter (Aller Futura - AF). Fish
      increased mean body weight 8 fold with PP- and AA-supplemented diets resulting in
      significantly higher weight gain than fish fed CON. Statistical analysis revealed
      a significant increase in relative PepT1 expression of fish fed experimental
      diets. Immunohistochemical staining with PepT1 antibody showed the presence of
      the transporter protein in the brush border membrane of the proximal intestinal
      enterocytes of fish from all experimental groups. Leptin immunoreactivity
      occurred not only in the gastric glands but also in proximal intestine and
      pyloric caeca of fish fed PP, AA and AF diets. Leptin immunoreactivity was also
      observed in hepatocyte cytoplasm and pancreatic acinar cells. Gastrin/CCK
      immunoreactive cells were present in the proximal intestine and pyloric caeca.

PMID- 19854289
TI  - Isolation and biochemical characterisation of lipid rafts from Atlantic cod
      (Gadus morhua) intestinal enterocytes.
AB  - Lipid rafts are glycosphingolipid/cholesterol-enriched membrane microdomains that
      have been extensively studied during the past two decades. Our aim was to isolate
      and perform biochemical characterization of lipid rafts from the intestinal brush
      border membrane (BBM) of Atlantic cod (Gadus morhua) to confirm their existence
      in a cold-water species and compare their characteristics with lipid rafts from
      other species in terms of lipid and protein content. To validate the isolation
      process, we assayed marker enzymes for subcellular organelles, including alkaline
      phosphatase (AP) and leucine aminopeptidase (LAP), both well-known marker enzymes
      for BBM and lipid rafts. All biochemical methods showed enrichment of AP in both
      the BBM and lipid raft fractions. Proteomic studies were performed by MALDI-TOF
      mass spectrometry using trypsin digested SDS-PAGE samples. Various proteins were
      associated with the cod intestinal lipid raft preparation such as aminopeptidase
      N, prohibitin, and beta-actin. Lipid analysis with (31)P NMR and thin layer
      chromatography on BBMs and lipid rafts samples gave higher content of
      sphingomyelin than previously reported in the BBM and lower content of
      phosphatidylcholine. Furthermore, sphingomyelin was highly dominant in the lipid
      rafts together with cholesterol. The existence of lipid rafts containing
      previously reported lipid raft characteristics from the cod intestine has,
      therefore, been confirmed in a ray-finned fish for the first time to the best of
      our knowledge.

PMID- 19854290
TI  - Molecular characterization of trypsinogens and development of trypsinogen gene
      expression and tryptic activities in grass carp (Ctenopharyngodon idellus) and
      topmouth culter (Culter alburnus).
AB  - This study examined the gene structures and expression of trypsinogens, as well
      as the trypsin activities of the grass carp Ctenopharyngodon idellus
      (herbivorous) and the topmouth culter Culter alburnus (carnivorous), which are
      commercially important freshwater species of the family Cyprinidae in China.
      Isolated full-length trypsinogen cDNA clones were 869 bp and 857 bp. The deduced
      amino acid sequences were 242aa and 247aa long, both containing the highly
      conserved residues essential for serine protease catalytic and conformational
      maintenance. The results from isoelectric and phylogenetic analyses suggest that
      grass carp trypsinogen is grouped with teleost trypsinogen group I, while
      topmouth culter trypsinogen is grouped with group II. The expression pattern of
      trypsinogen mRNA was similar between these two species, appearing 2 days post
      hatching (dph) and reaching peaks at 11 and 23 dph. The trypsin-specific
      activities in both species were detected 2 dph and reached the major peaks at 8
      dph, however the minor peaks were observed at 20 dph in the grass carp and 17 dph
      in the topmouth culter. The trypsin-specific activity was significantly higher in
      the grass carp than in the topmouth culter, which may be attributed to the nature
      of their different nutritional habits.

PMID- 19854291
TI  - Polypoidal choroidal vasculopathy and neovascular age-related macular
      degeneration: same or different disease?
AB  - Neovascular age-related macular degeneration (nAMD) is the commonest cause of
      severe visual impairment in older adults in Caucasian white populations.
      Polypoidal choroidal vasculopathy (PCV) has been described as a separate clinical
      entity differing from nAMD and other macular diseases associated with subretinal
      neovascularization. It remains controversial as to whether or not PCV represents
      a sub-type of nAMD. This article summarizes the current literature on the
      clinical, pathophysiological and epidemiological features and treatment responses
      of PCV and compares this condition to nAMD. Patients with PCV are younger and
      more likely Asians, and eyes with PCV lack drusen, often present with
      serosanguinous maculopathy or hemorrhagic pigment epithelial detachment, and have
      differing responses to photodynamic therapy and anti-vascular endothelial growth
      factor (VEGF) agents. There are also significant differences in angiographic and
      optical coherence tomography features between PCV and nAMD. Histopathological
      studies suggest differences in the anatomical details of the associated vascular
      abnormalities in the retina and choroids and the relative role of VEGF. There is
      emerging evidence of common molecular genetic determinants involving complement
      pathway and common environmental risk factors (e.g. smoking). Such information
      could further assist clinicians involved in the care of elderly patients with
      these conditions.

PMID- 19854292
TI  - The role of kindlins in cell biology and relevance to human disease.
AB  - The kindlins represent a class of focal adhesion proteins implicated in integrin
      activation. They comprise three evolutionarily conserved members, kindlin-1,
      kindlin-2 and kindlin-3, that share considerable sequence and structural
      similarities. The kindlins have a bipartite FERM (four point one protein, ezrin,
      radixin, moesin) domain interrupted by a pleckstrin homology domain and can bind
      directly to various classes of integrins as well as participate in inside-out
      integrin activation. They are encoded by three different genes, namely KIND1
      (FERMT1; chromosome 20p12.3), KIND2 (FERMT2; chromosome 14q22.1) and KIND3
      (FERMT3; chromosome 11q13.1). Loss-of-function mutations in KIND1 and KIND3 cause
      Kindler syndrome and leukocyte adhesion deficiency-III syndrome, respectively,
      although no human disease has yet been associated with KIND2 gene pathology. In
      this review, we focus on the cellular functions of the kindlins and their
      clinical relevance.

PMID- 19854293
TI  - Acquisition of SOX transcription factor specificity through protein-protein
      interaction, modulation of Wnt signalling and post-translational modification.
AB  - SOX transcription factors contain a high mobility group (HMG) box that confers
      sequence-specific (in the case of SOX/TCF) DNA binding ability to the protein.
      SOX proteins are transcriptional regulators involved in diverse tissues and
      developmental processes. Based on protein sequence comparisons, the SOX family is
      divided into eight groups. SOX proteins belonging to the same group tend to have
      overlapping tissue expression profiles and are able to functionally substitute
      for one another. However, SOX proteins belonging to different groups often do not
      show redundant regulatory functions. To achieve their specific actions, SOX
      proteins rely on interactions with a wide variety of proteins. The choice of
      binding partners as well as post-translational modifications of SOX proteins
      confers target gene specificity to the HMG box proteins which otherwise have weak
      DNA binding specificity. SOX proteins also regulate signalling pathways, such as
      the Wnt pathway by interacting with beta-catenin and/or TCF/LEF transcription
      factors, employing different mechanisms to achieve similar functional outcomes.
      Here we review extensively the SOX protein interactions with partner co-factors,
      the ability of SOX proteins to modulate Wnt signalling and the effect of post
      translational modification of SOX proteins on their function.

PMID- 19854294
TI  - Integrated genomics of chemotherapy resistant ovarian cancer: a role for
      extracellular matrix, TGFbeta and regulating microRNAs.
AB  - Epithelial ovarian cancer is the sixth most common cancer in women worldwide and
      the most important cause of death from gynaecological cancers in the Western
      world. Our explorative pathway analysis on seven published gene-sets associated
      with platinum resistance in ovarian cancer reveals TP53 and transforming growth
      factor beta as key genes. Furthermore, the extracellular matrix was associated
      with chemotherapy resistance in ovarian cancer as well as endocrine resistance in
      breast cancer. Pathway analysis again revealed transforming growth factor beta as
      a key gene regulating extracellular matrix gene expression. A model is presented
      based on literature linking transforming growth factor beta, extracellular
      matrix, integrin signalling, epithelial to mesenchymal transition and regulating
      microRNAs with a (bivalent) role in chemotherapy response.

PMID- 19854295
TI  - The quest for biomarkers in tuberculosis.
AB  - No new vaccine has been licensed for tuberculosis (TB) for more than three
      quarters of a century, and no new drug has been licensed for half a century. One
      major drawback has been the attrition caused by the lack of a reliable biological
      indicator (biomarker) to predict toxicity and efficacy early in the development
      pipeline. This review portrays the landscape of biomarker discovery for TB in the
      context of drug and vaccine development using emerging global biomics platforms.
      The time is ripe to move from single markers for correlates of protection to a
      biosignature comprising a well-defined set of robust indicators in TB that can
      accelerate rapid screening and early selection of potential drug and vaccine
      candidates.

PMID- 19854297
TI  - Arthropod phylogeny: an overview from the perspectives of morphology, molecular
      data and the fossil record.
AB  - Monophyly of Arthropoda is emphatically supported from both morphological and
      molecular perspectives. Recent work finds Onychophora rather than Tardigrada to
      be the closest relatives of arthropods. The status of tardigrades as
      panarthropods (rather than cycloneuralians) is contentious from the perspective
      of phylogenomic data. A grade of Cambrian taxa in the arthropod stem group
      includes gilled lobopodians, dinocaridids (e.g., anomalocaridids), fuxianhuiids
      and canadaspidids that inform on character acquisition between Onychophora and
      the arthropod crown group. A sister group relationship between Crustacea (itself
      likely paraphyletic) and Hexapoda is retrieved by diverse kinds of molecular data
      and is well supported by neuroanatomy. This clade, Tetraconata, can be dated to
      the early Cambrian by crown group-type mandibles. The rival Atelocerata
      hypothesis (Myriapoda+Hexapoda) has no molecular support. The basal node in the
      arthropod crown group is embroiled in a controversy over whether myriapods unite
      with chelicerates (Paradoxopoda or Myriochelata) or with crustaceans and hexapods
      (Mandibulata). Both groups find some molecular and morphological support, though
      Mandibulata is presently the stronger morphological hypothesis. Either hypothesis
      forces an unsampled ghost lineage for Myriapoda from the Cambrian to the mid
      Silurian.

PMID- 19854296
TI  - Arthropod phylogeny revisited, with a focus on crustacean relationships.
AB  - Higher-level arthropod phylogenetics is an intensely active field of research,
      not least as a result of the hegemony of molecular data. However, not all areas
      of arthropod phylogenetics have so far received equal attention. The application
      of molecular data to infer a comprehensive phylogeny of Crustacea is still in its
      infancy, and several emerging results are conspicuously at odds with morphology
      based studies. In this study, we present a series of molecular phylogenetic
      analyses of 88 arthropods, including 57 crustaceans, representing all the major
      lineages, with Onychophora and Tardigrada as outgroups. Our analyses are based on
      published and new sequences for two mitochondrial markers, 16S rDNA and
      cytochrome c oxidase subunit I (COI), and the nuclear ribosomal gene 18S rDNA. We
      designed our phylogenetic analyses to assess the effects of different strategies
      of sequence alignment, alignment masking, nucleotide coding, and model settings.
      Our comparisons show that alignment optimization of ribosomal markers based on
      secondary structure information can have a radical impact on phylogenetic
      reconstruction. Trees based on optimized alignments recover monophyletic
      Arthropoda (excluding Onychophora), Pancrustacea, Malacostraca, Insecta,
      Myriapoda and Chelicerata, while Maxillopoda and Hexapoda emerge as paraphyletic
      groups. Our results are unable to resolve the highest-level relationships within
      Arthropoda, and none of our trees supports the monophyly of Myriochelata or
      Mandibulata. We discuss our results in the context of both the methodological
      variations between different analyses, and of recently proposed phylogenetic
      hypotheses. This article offers a preliminary attempt to incorporate the large
      diversity of crustaceans into a single molecular phylogenetic analysis, assessing
      the robustness of phylogenetic relationships under varying analysis parameters.
      It throws into sharp relief the relative strengths and shortcomings of the
      combined molecular data for assessing this challenging phylogenetic problem, and
      thereby provides useful pointers for future studies.

PMID- 19854298
TI  - Tracing the trilobite tree from the root to the tips: a model marriage of fossils
      and phylogeny.
AB  - Trilobites are a highly diverse group of extinct arthropods that persisted for
      nearly 300 million years. During that time, there was a profusion of
      morphological form, and they occupied a plethora of marine habitats. Their
      diversity, relative abundance, and complex morphology make them excellent
      candidates for phylogenetic analysis, and partly as a consequence they have been
      the subject of many cladistic studies. Although phylogenetic knowledge is
      certainly incomplete, our understanding of evolutionary patterns within the group
      has dramatically increased over the last 30 years. Moreover, trilobites have
      formed an important component of various studies of macroevolutionary processes.
      Here, we summarize the phylogenetic breadth of knowledge on the Trilobita, and
      present various hypotheses about phylogenetic patterns within the group, from the
      highest to the lowest taxonomic levels. Key topics we consider include the
      question of trilobite monophyly, the phylogenetic position of trilobites vis a
      vis extant arthropod groups, and inter- and intra-ordinal relationships.

PMID- 19854299
TI  - Anti-angiogenic activity of triptolide in anaplastic thyroid carcinoma is
      mediated by targeting vascular endothelial and tumor cells.
AB  - Triptolide is confirmed to suppress angiogenesis of anaplastic thyroid carcinoma.
      Here we further expound the precise mechanism involved in this activity.
      Triptolide downregulated nuclear factor kappa B (NF-kappaB) pathway and its
      targeting genes associated with endothelial cell mobilization in human umbilical
      vein endothelial cells (HUVECs) and impaired VEGF expression in thyroid carcinoma
      TA-K cells. Furthermore, both triptolide and the conditioned medium from
      triptolide-treated TA-K cells (CMT) significantly attenuated proliferation,
      migration and tube formation of HUVECs. In vivo, triptolide inhibited TA-K cell
      induced tumor growth, vascular formation and VEGF expression. Our data establish
      that triptolide inhibits tumor angiogenesis by the dual action on vascular
      endothelial cells and tumor cells, thus providing a novel and overall explanation
      for the anti-angiogenesis action of triptolide. The multicellular targets
      emphasize triptolide as a high-performance and potential angiogenesis inhibitor.

PMID- 19854300
TI  - Gene therapy in autoimmune diseases: challenges and opportunities.
AB  - Clinical treatment of autoimmune disorders presents a special challenge. For
      decades, most clinical regimens in autoimmunity has been largely symptomatic and
      non-disease specific. Although data from vigorous research has lead to
      accumulating knowledge on the pathogenic and immunological mechanisms of many
      autoimmune diseases, their direct clinical applications have been sparse.
      Advances in biotechnology have laid the groundwork for potent and specific
      molecular targeting therapies by gene therapy, and have just begun to be
      investigated in the treatment of autoimmune disorders. Such work has been largely
      based on the availability of well-established animal models of common autoimmune
      disorders, and the efficacy of strategic approaches initially investigated and
      validated in these models. Although these preclinical animal model studies have
      provided the proof-of-concept for multiple potential applications, human clinical
      trials on gene therapy in autoimmunity are still at its infancy. The recent
      success of Phase I/II clinical trials of gene therapy in rheumatoid arthritis and
      multiple sclerosis, development of cutting edge technology in target
      identification, as well as gene delivery systems have now set the stage for a
      more thorough and vigorous pace in the near future to advance this exciting
      field.

PMID- 19854301
TI  - Autoimmune diseases induced by biological agents: a double-edged sword?
AB  - Biological agents are increasingly used for a rapidly-expanding number of
      rheumatic and systemic autoimmune diseases, with a growing number of reports of
      the paradoxical induction of autoimmune processes, overwhelmingly associated with
      anti-TNF agents. In this review, we analyze the clinical characteristics and
      outcomes of autoimmune diseases developing after biological therapies through a
      baseline Medline search as one of the objectives of the BIOGEAS project, created
      by the Spanish Society of Internal Medicine. The latest update of our registry
      (15 July 2009) included more than 800 cases of autoimmune diseases secondary to
      biological therapies, including a wide variety of both systemic (lupus,
      vasculitis, sarcoidosis and antiphospholipid syndrome) and organ-specific
      (interstitial lung disease, uveitis, optic neuritis, peripheral neuropathies,
      multiple sclerosis and autoimmune hepatitis) autoimmune processes. The majority
      of cases appeared between one month and one year after initiation of the
      biological agent and complete resolution was observed in nearly 75% of cases
      after cessation of therapy. The induced autoimmune diseases with the poorest
      outcomes were interstitial lung disease, inflammatory ocular disease and central
      nervous system demyelinating diseases.

PMID- 19854303
TI  - Manipulation of process parameters to achieve different ternary phase
      microparticle configurations.
AB  - Ternary phase microparticles of poly(D,L-lactide-co-glycolide) (50:50), poly(L
      lactide) and poly(caprolactone) were fabricated through a one-step solvent
      evaporation technique. The purpose of this study was to examine the effects of
      various process parameters on the final configuration (i.e. polymer distribution
      and dimensions) of these composite microparticles and, subsequently, propose
      their mechanism of formation. Particle morphologies and configurations were
      determined using scanning electron microscopy, polymer dissolution tests and
      Raman mapping. It was found that a starting polymer solution prepared below the
      cloud point and an increased oil to water ratio will facilitate polymer
      configurations close to thermodynamic equilibrium, which is dictated by the
      interfacial energies of the components. By varying the polymer mass ratio or
      adjusting the precipitation rate, through stirring speed and oil to water ratio,
      a wide range of microparticles with different core-shell dimensions and embedded
      particulate sizes can also be fabricated. At the same time, lowering the polymer
      solution concentration and increasing the stirring speed may result in smaller
      microparticles. Correlation of these process parameters with the final composite
      particle morphology was thus established. This understanding should allow the
      controlled fabrication of ternary phase composite microparticles through a single
      step solvent evaporation technique.

PMID- 19854302
TI  - Insights into protein kinase regulation and inhibition by large scale structural
      comparison.
AB  - Protein structure determination of soluble globular protein domains has developed
      into an efficient routine technology which can now be applied to generate and
      analyze structures of entire human protein families. In the kinase area, several
      kinase families still lack comprehensive structural analysis. Nevertheless,
      Structural Genomics (SG) efforts contributed more than 40 kinase catalytic domain
      structures during the past 4 years providing a rich resource of information for
      large scale comparisons of kinase active sites. Moreover, many of the released
      structures are inhibitor complexes that offer chemical starting points for
      development of selective and potent inhibitors. Here we discuss the currently
      available structural data and strategies that can be utilized for the development
      of highly selective inhibitors.

PMID- 19854304
TI  - Effect of spleen surgeries on Escherichia coli distribution on the mononuclear
      phagocytic system.
AB  - OBJECTIVE: To avoid asplenic state, many approaches preserving the spleen have
      been proposed in the literature: splenorraphy, partial splenectomy with or
      without preservation of hilar vessels and splenic tissue auto-implants. Subtotal
      splenectomy, preserving the upper spleen pole nourished only by splenogastric
      vessels is an alternative when the splenic pedicle must be ligated. The purpose
      of this study was to evaluate the influence of partial, subtotal and total
      splenectomies on the distribution of Escherichia coli in the mononuclear
      phagocytic system. METHOD: Thirty-two rats divided into four groups were studied:
      sham operation (total spleen preservation), partial splenectomy, subtotal
      splenectomy and total splenectomy. Five weeks after surgeries, an aliquot of E.
      coli marked with tecnetium-99m was injected intravenously. The animals were
      killed 20min later and the spleen, lungs and liver were removed in order to
      determine the distribution of labeled bacteria. RESULTS: The amount of E. coli in
      the splenic tissue was greater in the intact spleen group than in the partial or
      subtotal splenectomy groups. Phagocytosis through the spleen did not differ
      between the partial and subtotal splenectomy groups. The amount of bacteria in
      the lungs was greater in the partial than in the subtotal splenectomy group. The
      distribution of labeled bacteria was greater in the liver of animals submitted to
      subtotal splenectomy than in the other groups. CONCLUSION: The upper splenic
      pole, supplied only by splenogastric vessels, has the ability to remove live
      bacteria from the blood stream, showing that effective blood clearance occurs
      even without vascularization through the splenic pedicle. Thus, the distribution
      of E. coli through the mononuclear phagocytic system shows different behavior
      depending on the type of splenectomy to which the animals are submitted.

PMID- 19854305
TI  - Complementary and alternative medicine (CAM) and cancer: the kind face of
      complementary medicine.

PMID- 19854306
TI  - Specific detection of benzimidazole resistance in Colletotrichum gloeosporioides
      from fruit crops by PCR-RFLP.
AB  - Anthracnose diseases, caused by Colletotrichum gloeosporioides, are a worldwide
      problem and are especially important in Taiwan owing to the severe economic
      damage they cause to tropical fruits that are grown for local consumption and
      export. Benzimidazoles are systemic fungicides widely used for controlling these
      diseases in Taiwan. Thirty-one isolates of C. gloeosporioides from mango and
      strawberry grown in Taiwan were examined for their sensitivity to benzimidazole
      fungicides. The responses of the isolates grown on benzimidazole-amended culture
      media were characterized as sensitive, moderately resistant, resistant or highly
      resistant. Analysis of point mutations in the beta-tubulin gene by DNA sequencing
      of PCR-amplified fragments revealed a substitution of GCG for GAG at codon 198 in
      resistant and highly resistant isolates and a substitution of TAC for TTC at
      codon 200 in moderately resistant isolates. A set of specific primers, TubGF1 and
      TubGR, was designed to amplify a portion of the beta-tubulin gene for the
      detection of benzimidazole-resistant C. gloeosporioides. Bsh1236I restriction
      maps of the amplified beta-tubulin gene showed that the resistant isolate
      sequence, but not the sensitive isolate sequence, was cut. The PCR restriction
      fragment length polymorphism (PCR-RFLP) was validated to detect benzimidazole
      resistant and benzimidazole-sensitive C. gloeosporioides isolates recovered from
      avocado, banana, carambola, dragon fruit, grape, guava, jujube, lychee, papaya,
      passion fruit and wax apple. This method has the potential to become a valuable
      tool for monitoring the occurrence of benzimidazole-resistant C. gloeosporioides
      and for assessment of the need for alternative management practices.

PMID- 19854307
TI  - Comparison of hip fracture risk prediction by femoral aBMD to experimentally
      measured factor of risk.
AB  - Areal BMD (aBMD) derived from DXA is currently the gold standard for diagnosis of
      osteoporosis. A biomechanical approach to fracture risk assessment comparing the
      ratio of applied load to bone strength, termed the factor of risk (Phi), may be
      useful to better identify patients at risk for fracture. We obtained 73 human
      cadaveric femurs (48 women and 25 men, aged 74.2+/-8.7 years, range 55-98 years),
      measured femoral neck (FN) aBMD by DXA, and mechanically tested the femurs to
      failure in a sideways fall configuration. The force applied to the hip during a
      sideways fall was estimated from height and weight, and accounted for
      trochanteric soft tissue thickness. Compared to men, women had significantly
      lower FN aBMD and femoral strength, and tended to have higher factor of risk for
      hip fracture Phi. Fifty-three of 54 (98%) specimens that had a FN aBMD T-score
      below -2.5 also had a Phi>1. However, 10/19 (53%) specimens with FN aBMD T-score
      above -2.5 also had Phi>1. These data indicate that whereas an aBMD-based
      diagnosis of osteoporosis is highly associated with fracture risk as assessed by
      the factor of risk, about 50% of individuals not designated as osteoporotic by
      aBMD testing would be at high risk for hip fracture should they experience a
      sideways fall. These findings strongly support the investigation of new
      biomechanically-based methods of fracture risk prediction.

PMID- 19854309
TI  - Extraordinary hypertension after a lunar mission.

PMID- 19854308
TI  - International longitudinal pediatric reference standards for bone mineral
      content.
AB  - To render a diagnosis pediatricians rely upon reference standards for bone
      mineral density or bone mineral content, which are based on cross-sectional data
      from a relatively small sample of children. These standards are unable to
      adequately represent growth in a diverse pediatric population. Thus, the goal of
      this study was to develop sex and site-specific standards for BMC using
      longitudinal data collected from four international sites in Canada and the
      United States. Data from four studies were combined; Saskatchewan Paediatric Bone
      Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young
      Women's Health Study (n=112) and Stanford's Bone Mineral Accretion study (n=423).
      Males and females (8 to 25 years) were measured for whole body (WB), total
      proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were
      analyzed using random effects models. Bland-Altman was used to investigate
      agreement between predicted and actual data. Age, height, weight and ethnicity
      independently predicted BMC accrual across sites (P<0.05). Compared to White
      males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g
      less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age,
      height and weight controlled. We report similar findings for the PF and FN.
      Models for females for all sites were similar with age, height and weight as
      independent significant predictors of BMC accrual (P<0.05). We provide a tool to
      calculate a child's BMC Z-score, accounting for age, size, sex and ethnicity. In
      conclusion, when interpreting BMC in pediatrics we recommend standards that are
      sex, age, size and ethnic specific.

PMID- 19854310
TI  - Guidelines for bedside teaching.

PMID- 19854311
TI  - 64-slice multidetector computed tomography (MDCT) reduces other diagnostic
      studies for coronary artery disease.

PMID- 19854312
TI  - Regarding the coexistence of Cullen's and Grey Turner's signs in acute
      pancreatitis.

PMID- 19854314
TI  - Catastrophic complication of chiropractic manipulation: a report of
      quadriparesis.

PMID- 19854315
TI  - Pulmonary langerhans' cell histiocytosis.

PMID- 19854316
TI  - Stuck in the wrong place.

PMID- 19854317
TI  - Chronic diarrhea responding to proton pump inhibitors: a clinical sign of
      Zollinger-Ellison syndrome.

PMID- 19854318
TI  - Back to the future: medical students can matter again.

PMID- 19854319
TI  - Should we maintain an open mind about homeopathy?

PMID- 19854320
TI  - Medicare's new regulations for deep vein thrombosis as a "never event": wise or
      worrisome?

PMID- 19854322
TI  - Assessing fracture risk and effects of osteoporosis drugs: bone mineral density
      and beyond.
AB  - Although there have been numerous advances in the assessment of bone strength and
      fracture risk, the majority of these techniques can only be performed in research
      laboratories, making them largely unavailable to practicing clinicians.
      Prospective epidemiologic studies have identified risk factors that can be
      assessed within the clinic and combined with bone mineral density to allow
      clinicians to better identify untreated individuals at heightened risk for
      fracture and to make informed treatment decisions based on 10-year absolute
      fracture risk. This article discusses the assessment of fracture risk in clinical
      practice, reviews currently and soon-available bone measurement tools, and
      details the impacts of osteoporosis therapies on fracture risk.

PMID- 19854323
TI  - Improving pregnancy counseling for women with rheumatoid arthritis taking
      methotrexate.

PMID- 19854321
TI  - An umbrella review: corticosteroid therapy for adults with acute asthma.
AB  - The objective of this "umbrella" review is to synthesize the evidence and provide
      clinicians a single report that summarizes the state of knowledge regarding the
      use of corticosteroids in adults with acute asthma. Systematic reviews in the
      Cochrane Library and additional clinical trials published in English from 1966 to
      2007 in MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL, and references from
      bibliographies of pertinent articles were reviewed. Results indicate that the
      evidence base is frequently limited to small, single-center studies. Findings
      suggest that therapy with systemic corticosteroids accelerates the resolution of
      acute asthma and reduces the risk of relapse. There is no evidence that
      corticosteroid doses greater than standard doses (prednisone 50-100 mg
      equivalent) are beneficial. Oral and intravenous corticosteroids, as well as
      intramuscular and oral corticosteroid regimens, seem to be similarly effective. A
      nontapered 5- to 10-day course of corticosteroid therapy seems to be sufficient
      for most discharged patients. Combinations of oral and inhaled corticosteroids on
      emergency department/hospital discharge might minimize the risk of relapse.

PMID- 19854324
TI  - A prolonged, perplexing pyrexia.

PMID- 19854325
TI  - Wiped out.

PMID- 19854326
TI  - Not what she had in mind.

PMID- 19854327
TI  - Clues to a life-threatening disease.

PMID- 19854328
TI  - Sign of three.

PMID- 19854329
TI  - Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal
      women.
AB  - BACKGROUND: There is uncertainty over the risks and benefits of hormone therapy.
      We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy
      on total mortality in younger postmenopausal women. This analysis synthesizes
      evidence from different sources, taking into account varying views on the issue.
      METHODS: A comprehensive search from 1966 through January 2008 identified
      randomized controlled trials of at least 6 month's duration that evaluated
      hormone therapy in women with mean age <60 years and reported at least one death,
      and prospective observational cohort studies that evaluated the relative risk of
      mortality associated with hormone therapy after adjustment for confounding
      variables. RESULTS: The results were synthesized using a hierarchical random
      effects Bayesian meta-analysis. The pooled results from 19 randomized trials,
      with 16,000 women (mean age 55 years) followed for 83,000 patient-years, showed a
      mortality relative risk of 0.73 (95% credible interval 0.52-0.96). When data from
      8 observational studies were added to the analysis, the resultant relative risk
      was 0.72 (credible interval 0.62-0.82). The posterior probability that hormone
      therapy reduces total mortality in younger women is almost 1. CONCLUSIONS: The
      synthesis of data using Bayesian meta-analysis indicates a reduction in mortality
      in younger postmenopausal women taking hormone therapy compared with no
      treatment. This finding should be interpreted taking into account the potential
      benefits and harms of hormone therapy.

PMID- 19854330
TI  - Risk factors for heart failure: a population-based case-control study.
AB  - BACKGROUND: The relative contribution of risk factors to the development of heart
      failure remains controversial. Further, whether these contributions have changed
      over time or differ by sex is unclear. Few population-based studies have been
      performed. We aimed to estimate the population attributable risk (PAR) associated
      with key risk factors for heart failure in the community. METHODS: Between 1979
      and 2002, 962 incident heart failure cases in Olmsted County were age and sex
      matched to population-based controls using Rochester Epidemiology Project
      resources. We determined the frequency of risk factors (coronary heart disease,
      hypertension, diabetes mellitus, obesity, and smoking), odds ratios, and PAR of
      each risk factor for heart failure. RESULTS: The mean number of risk factors for
      heart failure per case was 1.9 + or - 1.1 and increased over time (P<.001).
      Hypertension was the most common (66%), followed by smoking (51%). The prevalence
      of hypertension, obesity, and smoking increased over time. The risk of heart
      failure was particularly high for coronary disease and diabetes with odds ratios
      (95% confidence intervals) of 3.05 (2.36-3.95) and 2.65 (1.98-3.54),
      respectively. However, the PAR was highest for coronary disease and hypertension;
      each accounted for 20% of heart failure cases in the population, although
      coronary disease accounted for the greatest proportion of cases in men (PAR 23%)
      and hypertension was of greatest importance in women (PAR 28%). CONCLUSION:
      Preventing coronary disease and hypertension will have the greatest population
      impact in preventing heart failure. Sex-targeted prevention strategies might
      confer additional benefit. However, these relationships can change, underscoring
      the importance of continued surveillance of heart failure.

PMID- 19854332
TI  - Prevalence and severity of undiagnosed urinary incontinence in women.
AB  - BACKGROUND: Urinary incontinence is a highly prevalent condition in aging women
      that results in significant morbidity. Less than half of women who suffer from
      urinary incontinence seek treatment, resulting in a significant proportion of
      clinically relevant urinary incontinence remaining undiagnosed. Therefore, the
      purpose of this study was to quantify the prevalence of urinary incontinence in
      undiagnosed women in a managed care population. METHODS: There were 136,457 women
      aged 25-80 years enrolled in Kaiser Permanente Northwest who were free of
      genitourinary diagnoses, including urinary incontinence, who were included in
      this study. Of the 2118 women who were mailed questionnaires ascertaining
      information on demographic and urinary incontinence characteristics, 875
      completed the survey. A chart review of the 234 women who reported moderate to
      severe urinary incontinence was performed. RESULTS: The prevalence of undiagnosed
      urinary incontinence was 53% in the preceding year, and 39% in the preceding
      week. The prevalence of undiagnosed stress, mixed, and urge incontinence was
      found to be 18.7%, 12.0%, and 6.8%, respectively. Quality of life was found to
      significantly decrease with increasing urinary incontinence severity. Of the 234
      chart-reviewed women, 5% were found to have physician-documented urinary
      incontinence. CONCLUSIONS: These results suggest that a significant proportion of
      women in this managed care population are suffering from urinary incontinence
      that remains undiagnosed. Efforts should be made to encourage women and
      physicians to initiate conversations about urinary incontinence symptoms in order
      to decrease the unnecessary burden of this disease.

PMID- 19854331
TI  - Recommendation of low-salt diet and short-term outcomes in heart failure with
      preserved systolic function.
AB  - BACKGROUND: Dietary sodium indiscretion frequently contributes to
      hospitalizations in elderly heart failure patients. Animal models suggest an
      important role for dietary sodium intake in the pathophysiology of heart failure
      with preserved systolic function. The documentation and effects of hospital
      discharge recommendations, particularly for sodium-restricted diet, have not been
      extensively investigated in heart failure with preserved systolic function.
      METHODS: We analyzed 1700 heart failure admissions to Michigan community
      hospitals. We compared documentation of guideline-based discharge recommendations
      between preserved systolic function and systolic heart failure patients with chi
      squared testing, and used logistic regression to identify predictors of 30-day
      death and hospital readmission in a prespecified follow-up cohort of 443 patients
      with preserved systolic function. We hypothesized that patients who received a
      documented discharge recommendation for sodium-restricted diet would have lower
      30-day adverse event rates. RESULTS: Heart failure patients with preserved
      systolic function were significantly less likely than systolic heart failure
      patients to receive discharge recommendations for weight monitoring (33% vs 43%)
      and sodium-restricted diet (42% vs 53%). Upon propensity score-adjusted
      multivariable analysis, patients with preserved systolic function who received a
      documented sodium-restricted diet recommendation had decreased odds of 30-day
      combined death and readmission (odds ratio 0.43, 95% confidence interval, 0.24
      0.79; P=.007). No other discharge recommendations predicted 30-day outcomes.
      CONCLUSIONS: Clinicians document appropriate discharge instructions less
      frequently in heart failure with preserved systolic function than systolic heart
      failure. Selected heart failure patients with preserved systolic function who
      receive advice for sodium-restricted diet may have improved short-term outcomes
      after hospital discharge.

PMID- 19854333
TI  - A(1c) control in a primary care setting: self-titrating an insulin analog pre-mix
      (INITIATEplus trial).
AB  - PURPOSE: To study glycemic control and hypoglycemia development upon initiation
      of insulin through a self-titration schedule in a 24-week trial, conducted with
      4875 insulin-naive patients with poorly controlled type 2 diabetes, predominantly
      in a primary care setting. METHODS: Subjects initiated twice-daily biphasic
      insulin aspart 70/30 with 6 units prebreakfast and 6 units presupper, self
      titrating according to self-measured blood glucose values. Subjects were
      randomized (1:1:1) to telephone counseling provided by a registered dietician: no
      counseling (NC), 1 counseling session (1C), or 3 sessions (3C). RESULTS: Mean
      baseline HbA(1c) (9.9% across groups) decreased approximately 2.5% to 7.49% + or 
      1.48, 7.48% + or - 1.50, and 7.44% + or - 1.46 in the NC, 1C, and 3C groups,
      respectively. Within these groups, a hemoglobin A(1c) (HbA(1c)) value <7% was
      achieved by 40.2%, 41.6%, and 41.8% of subjects, respectively. Eight-point blood
      glucose profiles were substantially improved from baseline for all groups.
      Hypoglycemia was experienced by 10.2%-11.4% of the subjects in each group. Rates
      of minor and major hypoglycemia were low but decreased as dietary counseling
      increased (minor hypoglycemia: 56 vs 50 vs 45 episodes per 100 patient-years;
      major hypoglycemia, 9 vs 6 vs 4 episodes per 100 patient-years, for the NC vs 1C
      vs 3C groups, respectively; P <.001, 3C vs NC). Weight increased by 3.13, 3.40,
      and 2.88 kg for the NC, 1C, and 3C groups, respectively. CONCLUSION: In the
      primary care setting, self-titration of biphasic insulin aspart 70/30 was
      effective in achieving recommended HbA(1c) goals even with minimal dietary
      counseling.

PMID- 19854334
TI  - Reducing blood sample hemolysis at a tertiary hospital emergency department.
AB  - PURPOSE: To determine the causes for sample hemolysis and measure the effect of
      an intervention to reduce sample hemolysis in the Emergency Department of a large
      hospital. METHODS: We conducted a phased, prospective, interventional study. In
      phase 1, factors associated with urea and electrolyte sample lysis were studied.
      Based on these results and a literature review, an educational program consisting
      of a 15-minute presentation was implemented. In phase 2, questionnaires were
      distributed to the doctors and medical students conducting blood sampling, and
      outcome data were collected after the samples were processed. RESULTS: In phase 1
      (n = 227), the use of a vacutainer was associated with the highest rates of
      hemolysis. Lysis rate was 35.8% with use of the vacutainer, compared with 11%
      without (adjusted odds ratio 6.0, 95% confidence interval, 2.3-15.2). In phase 2
      (n=204), the following significant changes were found: increased use of a syringe
      rather than vacutainer (before 64.3%; after 98.5%, P <.01), increased use of
      venipuncture for blood sampling (26%-36.8%, P = .02), reduced arterial sampling
      (3.1%-0%, P = .02), increased sample volume (4.5-5.2 mL, P <.01) and reduced
      interval from sampling to analysis (60.8-48.4 minutes, P <.01). We were able to
      attain a reduction in sample hemolysis from 19.8% (before) to 4.9% (after) (P
      <.001). This would translate to a cost savings of SGD$834.40 (USD$556.30) per day
      at the emergency department and SGD$304,556 (USD$203,037) per year. CONCLUSIONS:
      Introduction of an educational program at a hospital Emergency Department was
      able to significantly reduce rates of sample hemolysis.

PMID- 19854335
TI  - Diagnostic and prognostic value of uric acid in patients with acute dyspnea.
AB  - BACKGROUND: Uric acid was shown to predict outcome in patients with stable
      chronic heart failure. Its impact in patients admitted in the Emergency
      Department with acute dyspnea, however, remains unknown. METHODS: We
      prospectively investigated the diagnostic and prognostic value of uric acid in
      743 unselected patients presenting to the Emergency Department with acute
      dyspnea. RESULTS: Uric acid at admission was higher in patients with acute
      decompensated heart failure (51% of the cohort) as compared with patients with
      noncardiac causes of dyspnea (median, 447 micromol/L vs 340 micromol/L, P <.001).
      The area under the receiver operating characteristic curve for the accuracy to
      detect acute decompensated heart failure was inferior for uric acid (0.70) than
      for B-type natriuretic peptide (area under the receiver operating characteristic
      curve 0.91, P <.001). Patients in the highest uric acid tertile more often
      required admission to the hospital (92% vs 74% in the first tertile, P <.001) and
      had higher in-hospital mortality (13% vs 4% in the first tertile, P <.001).
      Cumulative 24-month mortality rates were 28% in the first, 31% in the second, and
      50% in the third tertile (P <.001). After adjustment in multivariable Cox
      proportional hazard analysis, uric acid predicted 24-month mortality
      independently of B-type natriuretic peptide (P=.003). CONCLUSIONS: Our study
      first shows that uric acid, measured at Emergency Department admission or
      hospital discharge, is a powerful predictor of long-term outcome in dyspneic
      patients.

PMID- 19854336
TI  - Quality of life after bariatric surgery: a population-based cohort study.
AB  - BACKGROUND: Bariatric surgery leads to profound weight loss, but postoperative
      complications and psychosocial issues may impact long-term quality of life. The
      primary aim of this project was to examine whether such patients have better
      quality of life and self-reported functional status compared with obese adults
      who do not have bariatric surgery. METHODS: This population-based study of
      patients evaluated for Roux-en-Y gastric bypass surgery involved a survey
      consisting of baseline and follow-up single-item overall quality-of-life items
      (Linear Analogue Self-Assessment Questionnaire; LASA), follow-up quality of life
      (Short-Form-12), and activity (Goldman's Specific Activity Scale). A total of 268
      and 273 surveys were mailed, with 148 (55.2%) operative and 88 (32.2%)
      nonoperative survey responders assessed, respectively. Linear regression was
      used, adjusting for changes in co-morbidity and functional status, to assess the
      differences in quality of life and activity level. Individual predictors of
      higher or better quality-of-life scores also were assessed. RESULTS: There were
      no major differences in baseline characteristics between survey responders and
      nonresponders. Mean follow-up was 4.0 and 3.8 years in the operative and
      nonoperative groups, respectively. The change in overall LASA from baseline to
      follow-up between groups was 3.1 + or - 0.4 (P <.001). The adjusted Short-Form-12
      score was 14.4 points higher in operative patients (P <.001) at follow-up.
      Operative patients had symptomatic improvement as measured by Specific Activity
      Scale status (odds ratio 7.5, P <.001) and self-reported exercise tolerance (odds
      ratio 2.61, P = .01) at follow-up compared with nonoperative patients. Predictors
      of a high follow-up LASA (P <.05) included initial treatment for depression,
      percent of weight lost, and absence of dyslipidemia and cardiovascular disease.
      Follow-up Short-Form-12 predictors included percent of weight loss, absence of
      baseline diabetes, baseline depression treatment, and follow-up cardiovascular
      disease. CONCLUSIONS: Profound weight loss after bariatric surgery, seeking
      treatment for depression, and absence of medical co-morbidities appears to
      predict better quality of life and self-reported functional status.

PMID- 19854337
TI  - Adequacy of vitamin D replacement in severe deficiency is dependent on body mass
      index.
AB  - BACKGROUND: Obesity is associated with hypovitaminosis D. Whether body mass index
      (BMI) determines the replacement dose of vitamin D to achieve sufficiency is
      unclear. OBJECTIVE: To determine the relationship between BMI and serum 25-OH
      vitamin D concentrations and whether the increase in serum 25-OH vitamin D
      concentrations with vitamin D replacement is dependent on BMI. METHODS:
      Retrospective review of anthropometric data and serum 25-OH vitamin D
      concentrations in 95 patients attending an outpatient clinic in a tertiary
      hospital. In a second component of the study, 17 hospital inpatients with severe
      vitamin D deficiency (serum 25-OH D concentrations<6 ng/mL [15 nmol/L]) were
      supplemented with 10,000 units vitamin D(3)/day orally for 1 week. Biochemistry
      and anthropometric measurements were compared before and after vitamin D
      replacement. RESULTS: Serum 25-OH vitamin D concentrations correlated negatively
      with BMI in the 95 outpatients (r(2) = 0.11, P <.01). In the longitudinal study,
      BMI correlated positively with serum intact parathyroid hormone (r(2) = 0.84, P
      <.01) and negatively with 1.25-(OH)(2) vitamin D (r(2) = 0.19, P=.06) at
      baseline. Serum 25-OH D concentrations achieved following 1 week of vitamin D(3)
      replacement correlated negatively with BMI (r(2) = 0.63, P <.01). CONCLUSION:
      Efficacy of vitamin D supplementation is dependent on BMI. Overweight and obese
      patients with hypovitaminosis D might require higher doses of vitamin D to
      achieve vitamin D repletion compared with individuals with normal body weight.

PMID- 19854338
TI  - Jumpstarting academic careers with a novel intern research rotation: the AIMS
      rotation.

PMID- 19854339
TI  - Glyphosate and glufosinate detection at electrogenerated NiAl-LDH thin films.
AB  - An amperometric sensor based on Ni(1-x)Al(x)(OH)(2)NO(3x).nH(2)O layered double
      hydroxide (LDH) has been developed for the electrochemical analysis in one step
      of two herbicides: glyphosate (N-(phosphonomethyl)glycine, Glyp) and glufosinate
      ((DL-homoalanine-4-yl)-methylphosphinic acid, Gluf). NiAl-LDH was prepared by
      coprecipitation or by electrodeposition at the Pt electrode surface. Inorganic
      films were fully characterized by X-ray diffraction, Raman spectroscopy and
      scanning electron microscopy. Adsorption isotherms of Glyp onto this inorganic
      lamellar material have been established. Electrocatalytic oxidation of Glyp and
      Gluf is possible at the Ni(3+) centres of the structure. The electrochemical
      responses of the NiAl-LDH modified electrode were obtained by cyclic voltammetry
      and chronoamperometry at 0.49V/SCE as a function of herbicide concentration in
      0.1M NaOH solution. The electrocatalytic response showed a linear dependence on
      the Glyp concentration ranging between 0.01 and 0.9mM with a detection limit of
      1muM and sensitivity 287mA/Mcm(2). The sensitivity found for Gluf was lower
      (178mA/Mcm(2)).

PMID- 19854340
TI  - Surface modification of polyacrylonitrile fiber for immobilization of antibodies
      and detection of analyte.
AB  - Pendent nitrile groups of multifilamentous polyacrylonitrile (PAN) fibers were
      reduced to amino groups using lithium aluminum hydride for different time of
      reduction and amine content was estimated by performing acid-base titrations.
      Attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR)
      and Differential Scanning Calorimetry (DSC) were used for the characterization of
      the generated amino groups and thermal properties of the reduced fibers,
      respectively. The surface morphology of the fibers after reduction and
      immobilization was characterized using Scanning Electron Microscope (SEM). The
      newly formed amino groups of the fibers were activated by using glutaraldehyde
      for the covalent linking of Goat anti-Rabbit IgG-HRP (GAR-HRP) antibody enzyme
      conjugate. Modified PAN fibers were evaluated as a matrix for sandwich ELISA by
      using Goat anti-Rabbit antibody (GAR-IgG), Rabbit anti-Goat (RAG-IgG) as analyte
      and enzyme conjugate GAR-HRP. The fibers reduced for 24h were able to detect the
      analyte RAG-IgG at a concentration as low as 3.75ng mL(-1) with 12% skimmed milk
      as blocking reagent for the optimized concentration of primary antibody GAR-IgG
      3microg mL(-1) and peroxidase conjugate GAR-HRP dilution of 8000 fold. The
      sensitivity, specificity and reproducibility of the developed immunoassay was
      further established with antibodies present in human blood using Rabbit anti
      Human (RAH-IgG) antibody and the corresponding HRP enzyme conjugate. As low as
      0.1microL of human blood was sufficient to perform the assay with the modified
      fibers.

PMID- 19854341
TI  - Benzimidazole carbamate residues in milk: Detection by Surface Plasmon Resonance
      biosensor, using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and
      Safe) method for extraction.
AB  - A surface plasmon resonance (SPR) biosensor screening assay was developed and
      validated to detect 11 benzimidazole carbamate (BZT) veterinary drug residues in
      milk. The polyclonal antibody used was raised in sheep against a methyl 5(6)
      [(carboxypentyl)-thio]-2-benzimidazole carbamate protein conjugate. A sample
      preparation procedure was developed using a modified QuEChERS method. BZT
      residues were extracted from milk using liquid extraction/partition with a
      dispersive solid phase extraction clean-up step. The assay was validated in
      accordance with the performance criteria described in 2002/657/EC. The limit of
      detection of the assay was calculated from the analysis of 20 known negative milk
      samples to be 2.7mugkg(-1). The detection capability (CCbeta) of the assay was
      determined to be 5mugkg(-1) for 11 benzimidazole residues and the mean recovery
      of analytes was in the range 81-116%. A comparison was made between the SPR
      biosensor and UPLC-MS/MS analyses of milk samples (n=26) taken from cows treated
      different benzimidazole products, demonstrating the SPR-biosensor assay to be fit
      for purpose.

PMID- 19854342
TI  - Single crystal WO(3) nanoflakes as quartz crystal microbalance sensing layer for
      ultrafast detection of trace sarin simulant.
AB  - Tungsten oxide (WO(3)) nanoflakes were synthesized, and characterized by scanning
      electron microscopy, transmission electron microscopy and X-ray diffraction.
      Thermogravimetry and X-ray photoelectron spectroscopy demonstrate the existence
      of strongly bound surface water molecules on the surface of tungsten oxide
      nanoflakes. WO(3) nanoflake functionalized quartz crystal microbalance sensors
      were fabricated, and firstly used for detection of trace sarin simulant, dimethyl
      methylphosphonate (DMMP). The sensors have better reproducibility and stability
      as well as much shorter response (30s) and recovery time (73s) than those
      functionalized by conventional hydrogen-bond acidic branched copolymers. The
      strongly bound surface water molecules on the surface of WO(3) nanoflakes are
      believed to play a key role in achieving such excellent DMMP sensing
      characteristics.

PMID- 19854343
TI  - A multidimensional high performance liquid chromatography method coupled with
      amperometric detection using a boron-doped diamond electrode for the simultaneous
      determination of sulfamethoxazole and trimethoprim in bovine milk.
AB  - The development and validation of a multidimensional HPLC method using an on-line
      clean-up column coupled with amperometric detection employing a boron-doped
      diamond (BDD) electrode for the simultaneous determination of sulfamethoxazole
      (SMX) and trimethoprim (TMP) in bovine milk are presented. Aliquots of pre
      prepared skim-milk samples were directly injected into a RAM octyl-BSA column in
      order to remove proteins that otherwise would interfere with milk analysis. After
      exclusion of the milk proteins, SMX and TMP were transferred to the analytical
      column (an octyl column) and the separation of the compounds from one another and
      from other endogenous milk components was achieved. SMX and TMP were detected
      amperometrically at 1.25V vs. Ag/AgCl (3.0molL(-1) KCl). Results with good
      linearity in the concentration ranges 50-800 and 25-400microgL(-1) for SMX and
      TMP, respectively, were obtained and no fouling of the BDD electrode was observed
      within the experimental period of several hours. The intra- and inter-assay
      coefficients of variation were less than 10% for both drugs and the obtained LOD
      values for SMX and TMP were 25.0 and 15.0microgL(-1), respectively.

PMID- 19854344
TI  - On-line monitoring of nine haloacetic acid species at the microgL(-1) level using
      post-column reaction-ion chromatography with nicotinamide fluorescence.
AB  - A laboratory-built automated instrument is reported for on-line, near real-time
      monitoring of nine haloacetic acids species (HAA9) in drinking water. The device
      uses anion-exchange chromatography to separate the HAA9 species, followed by post
      column reaction with nicotinamide in basic solution with fluorescence detection.
      Method detection limits for HAA9 species ranged from 0.6 to 10.1microgL(-1), mean
      % recovery values ranged from 58 to 161%, and % relative standard deviation
      ranged from 3.5 to 32% while operating within a factor of 2.5-5 of the method
      detection limit. The bias between the proposed method and United States
      Environmental Protection Agency Method 552.3 was measured during two separate on
      line studies and using grab samples collected from different distribution
      systems. In general, the two methods showed good agreement with biases for HAA9
      of less than 10microgL(-1).

PMID- 19854345
TI  - Development and validation of an HPLC method for the determination of process
      related impurities in pridinol mesylate, employing experimental designs.
AB  - A simple high performance liquid chromatographic method for the determination of
      process-related impurities in bulk drug of the central anticholinergic compound
      pridinol mesylate, has been developed and validated. Spectroscopically
      characterized synthetic impurities were used as standards. The chromatographic
      separation was optimized employing an experimental design strategy, and was
      achieved on a C(18) column with a mobile phase containing 50mM potassium
      phosphate buffer (pH 6.4), MeOH and 2-propanol (20:69:11, v/v/v), delivered at a
      flow rate of 1.0mLmin(-1). UV detection was performed at 245nm. The optimized
      method was thoroughly validated, demonstrating to be selective, when the
      chromatogram was recorded with a diode-array detector and peak purities were
      evaluated (>0.9995). The method is robust and linear (r(2)>0.99) over the range
      0.05-2.5% (5-250% with regards to the 1% specification limit for both process
      related impurities); it is also precise, regarding repeatability (RSD</=1.5% for
      all of the analytes) and intermediate precision aspects and LOQ values for the
      impurities are below 0.01%. Method accuracy, evidenced by low bias of the results
      and analyte recoveries in the range of 99.1-102.7%, was assessed at five analyte
      concentration levels. The usefulness of the determination was also demonstrated
      through the analysis of different lots of pridinol mesylate bulk substance. The
      results indicate that the method is suitable for the quality control of the bulk
      manufacturing of pridinol mesylate drug substance.

PMID- 19854346
TI  - Screening of salbutamol residues in swine meat and animal feed by an enzyme
      immunoassay in Taiwan.
AB  - An ELISA was developed for routine examination for extensive monitoring and
      screening programs for the residues of salbutamol in swine serum, animal feed,
      meat, and meat-related products destined for human consumption in Taiwan.
      Objectives of the study were to investigate the use of a new immunoassay for the
      detection of salbutamol residues in swine meat and animal feed samples, and to
      compare with a commercial kit in field test screens. A fast, simple and reliable
      sample preparation method for the determination of salbutamol was established.
      Field trials with 222 swine meat and 120 animal feed samples that were taken from
      local meat markets, auction markets and feed mills. The application and the
      results of two ELISA kits (a homemade and a commercial kit) for the screening of
      salbutamol were presented. Adopting 2microg kg(-1) salbutamol as a cut-off value
      for swine meat, the commercial beta-agonist ELISA had a sensitivity of 85.3% and
      a specificity of 95.2% versus GC-MS at a cut-off of 2microg kg(-1). The homemade
      salbutamol ELISA had a sensitivity of 100% and a specificity of 90.9% and gave no
      false-negative rate results. Furthermore, adopting 20microg kg(-1) salbutamol as
      a cut-off value for animal feed, both the commercial and homemade ELISA showed
      100% sensitivity and 100% specificity of the assays. In conclusion, a sensitive,
      specific salbutamol polyclonal antibody-based ELISA has been developed that could
      serve as a rapid screening assay, and the detection of positive samples at the
      place of sampling can result in more effective control of the illegal use of beta
      agonists.

PMID- 19854347
TI  - High-performance liquid chromatographic method for determination of amino acids
      by precolumn derivatization with 4-chloro-3,5-dinitrobenzotrifluoride.
AB  - This work presents an high-performance liquid chromatography method for the
      determination of amino acids after precolumn derivatization with 4-chloro-3,5
      dinitrobenzotrifluoride (CNBF) which can readily react with both primary and
      secondary amines. The precolumn derivatization conditions, including the CNBF
      concentration, reaction pH, temperature and reaction time were investigated for
      method optimization. In pH 9.0 borate buffer, the reaction of amino acids with
      CNBF was carried out at 60 degrees C for 30min, the optimized concentration of
      CNBF was 70mmol L(-1) and the molar ratio of amino acids to CNBF was 1:5.25. The
      chromatographic separation of 19 amino acids derivatives was performed on a
      Kromasil ODS C(18) column (250mm x 4.6mm, 5microm) with good reproducibility, and
      ultraviolet detection was applied at 260 nm. The mobile phase was a mixture of
      phase A (acetonitrile) and phase B (acetate buffer, acetonitrile, triethylamine;
      82.8:17:0.2, pH 4.9), and the flow rate was 0.4mL min(-1). The separation of all
      the labeled amino acids was achieved within 45min at room temperature by gradient
      elution mode. The method linearity, calculated for each amino acid, had a
      correlation coefficient higher than 0.9979, in concentrations ranging from 9.60
      to 3330.00 micromol L(-1). The detection limits of amino acids were 2.40
      6.50micromol L(-1), at a signal-to-noise ratio of 3. The proposed method was
      applied for the determination of amino acids in beer with recoveries of 97.0
      103.9% and relative standard deviations of 2.62-4.22%, respectively. This method
      showed good accuracy and repeatability that can be used for the quantification of
      amino acids in real samples.

PMID- 19854348
TI  - Solid-phase extraction followed by liquid chromatography-tandem mass spectrometry
      for the determination of hydroxylated benzophenone UV absorbers in environmental
      water samples.
AB  - A procedure for the determination of six derivatives of 2-hydroxybenzophenone,
      used as UV absorbers, in water samples is presented. Compounds were first
      concentrated using a solid-phase extraction (SPE) cartridge and then selectively
      determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using
      electrospray ionization (ESI). The effect of different parameters on the
      performance of concentration and determination steps is discussed. The highly
      polar and acidic 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (BP-4) required
      the use of ammonium acetate as modifier during desorption of SPE cartridges and
      also to improve the performance of its separation in the LC column. Under
      optimized conditions, the proposed method provided limits of quantification from
      less than 1 to 32ngL(-1), depending on the compound and the type of water sample.
      Recoveries from the SPE step (83-105%) remained unaffected by the nature of the
      matrix; however, the efficiency of electrospray ionization was compound and
      sample dependant. Real sample analysis reflected the presence of three of the six
      investigated species (BP-4, 2-hydroxy-4-methoxybenzophenone, BP-3, and 2,4
      dihydroxybenzophenone, BP-1) in the aquatic environment, particularly in raw
      wastewater samples. In this latter matrix, BP-4 was the compound presenting the
      highest concentrations; moreover, it was poorly removed in sewage treatment
      plants and consequently it also appeared in river water.

PMID- 19854349
TI  - Report of the multisociety task force on GI training.
AB  - In summary, the task force recommends that the 4 gastroenterology/hepatology
      societies work with the ABIM to develop a competency-based curriculum that
      incorporates the Maintenance of Certification process to accommodate the need and
      desire for training and subsequent practice in specific areas of
      gastroenterology/hepatology. Given the increasing complexity of treating
      digestive diseases, allowing trainees the opportunity to develop enhanced ability
      and experience in specific disease areas or procedures will benefit patients. By
      developing these training pathways, training programs will need to measure the
      achievements of trainees in terms of specific defined competencies rather than
      the duration of training alone.

PMID- 19854350
TI  - The function, proteolytic processing, and histopathology of Met in cancer.
AB  - The hepatocyte growth factor (HGF) and its receptor, the Met receptor tyrosine
      kinase, form a signaling network promoting cell proliferation, invasion, and
      survival in normal and cancer cells. Improper regulation of this pathway is
      attributed to many cancer types through overexpression, activating mutations, or
      autocrine loop formation. Many studies describe the localization of Met as
      membranous/cytoplasmic, but some studies using antibodies targeted to the C
      terminal domain of Met report nuclear localization. This chapter seeks to
      highlight the histopathology and expression of Met in cancer and its association
      with clinicopathological characteristics. We also discuss recent studies of the
      proteolytic processing of Met and effects of the processing on the subcellular
      localization of Met. Finally, we comment on Met as a therapeutic target for
      cancer treatment.

PMID- 19854351
TI  - Managing tumor angiogenesis: lessons from VEGF-resistant tumors and wounds.
AB  - It is now well established both experimentally and clinically, that new blood
      vessel growth is required for tumors to grow beyond a few millimeters and
      metastasize [Folkman, J. (1995). In: Mendelsohn, L., Howley, P., Israel, A.
      (Eds.), The Molecular Basis of Cancer, WB Saunders Company, Philadelphia, pp. 206
      225]. Angiogenesis, the process of forming new blood vessels from preexisting
      vessels, provides the tumor with additional oxygen and nutrients for its
      continued growth. In addition, the proximity and increase in vascular density
      enhance the likelihood of tumor cells entering the bloodstream to eventually
      metastasize. Since the initial observations of Dr. Folkman in the late 1970s,
      research over the past 30 years has focused intensely on identifying points in
      which the angiogenic cycle can be disrupted and has become an important component
      of current therapies to limit tumor progression.

PMID- 19854354
TI  - Drosophila Myc.
AB  - Myc genes play a major role in human cancer, and they are important regulators of
      growth and proliferation during normal development. Despite intense study over
      the last three decades, many aspects of Myc function remain poorly understood.
      The identification of a single Myc homolog in the model organism Drosophila
      melanogaster more than 10 years ago has opened new possibilities for addressing
      these issues. This review summarizes what the last decade has taught us about Myc
      biology in the fruit fly.

PMID- 19854353
TI  - Hepatitis B virus X protein molecular functions and its role in virus life cycle
      and pathogenesis.
AB  - Despite the existence of effective vaccines, HBV infection remains a major health
      problem with 2 billion people infected worldwide. Among them, 350 million are
      chronically infected, a major risk factor for the development of hepatocellular
      carcinoma (HCC). There is a strong need to develop new and efficient treatments
      against chronic infection and HCC. It is therefore important to understand HBV
      replication and persistence as well as the role of HBV in liver carcinogenesis.
      This chapter focuses on the regulatory protein HBx which is thought to play a
      central role in HBV regulation and pathogenesis. HBx has been shown to modulate a
      myriad of viral and cellular functions, yet its role in virus replication and
      pathogenesis in infected individuals remains far from being completely
      understood.

PMID- 19854355
TI  - Vaccines and the world of child health.

PMID- 19854356
TI  - Enabling women in medicine to reach the top.

PMID- 19854352
TI  - The TRAIL to targeted therapy of breast cancer.
AB  - Breast cancers can be classified into those which express the estrogen (ER) and
      progesterone (PR) receptors, those with HER-2 amplification, and those without
      expression of ER, PR, or amplified HER-2 (referred to as triple-negative or basal
      like breast cancer). Tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) activates apoptosis upon binding to its receptors in many tumor types and
      the ligand and agonist antibodies are currently being studied in patients in
      clinical phases I and II trials. Cell line studies suggest that many breast
      cancer cell lines are very resistant to TRAIL-induced apoptosis. However, recent
      data suggest that a subset of triple-negative/basal-like breast cancer cells is
      sensitive to TRAIL as a single agent. In addition, many studies have demonstrated
      that resistance to TRAIL-mediated apoptosis in breast cancer cells can be
      overcome by combinations of TRAIL with chemotherapy, radiation, and various
      targeted agents. This chapter will discuss the current understanding of the
      mechanisms, which control TRAIL-mediated apoptosis in breast cancer cells. The
      preclinical data supporting the use of TRAIL ligands and agonistic antibodies
      alone and in combination in breast cancer will also be discussed.

PMID- 19854357
TI  - Mental health services for older people.

PMID- 19854358
TI  - Japan approves brain death to increase donors: will it work?

PMID- 19854359
TI  - NCEPOD report on acute kidney injury-must do better.

PMID- 19854361
TI  - Carol Greider: unravelling the science of telomeres and telomerase. Interview by
      Stephen Pincock.

PMID- 19854362
TI  - Pregnancy and H1N1 infection.

PMID- 19854364
TI  - Pregnancy and H1N1 infection.

PMID- 19854365
TI  - Artemisinin resistance on the Thai-Cambodian border.

PMID- 19854367
TI  - The myth of the virgin rape myth.

PMID- 19854368
TI  - Artemisinin resistance on the Thai-Cambodian border.

PMID- 19854369
TI  - Concurrency driving the African HIV epidemics: where is the evidence?

PMID- 19854371
TI  - Multimorbidity: another key issue for cardiovascular medicine.

PMID- 19854372
TI  - Have we reached a plateau in adjuvant breast cancer therapy?

PMID- 19854373
TI  - Intentional self-plagiarism.

PMID- 19854374
TI  - Dizziness and collapse? It's a steal!

PMID- 19854375
TI  - Krill oil supplementation increases plasma concentrations of eicosapentaenoic and
      docosahexaenoic acids in overweight and obese men and women.
AB  - Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in
      both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the
      hypothesis that krill oil would increase plasma concentrations of EPA and DHA
      without adversely affecting indicators of safety, tolerability, or selected
      metabolic parameters. In this randomized, double-blind parallel arm trial,
      overweight and obese men and women (N = 76) were randomly assigned to receive
      double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control
      (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations
      increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2
      +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/-
      30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and
      -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined
      significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than
      in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group
      (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea
      nitrogen declined in the krill oil group as compared with the menhaden oil group
      (P < .006). No significant differences for other safety variables were noted,
      including adverse events. In conclusion, 4 weeks of krill oil supplementation
      increased plasma EPA and DHA and was well tolerated, with no indication of
      adverse effects on safety parameters.

PMID- 19854377
TI  - Associations of n-6 and n-3 polyunsaturated fatty acids and tocopherols with
      proxies of membrane stability and subcutaneous fat sites in male elite swimmers.
AB  - We hypothesize that membrane stability of elite swimmers adapted to chronic
      intense training is dependent on polyunsaturated fatty acids (PUFAs) and
      tocopherols in blood pools and that the composition of PUFA in plasma
      nonesterified fatty acids (NEFAs) might be associated with specific subcutaneous
      fat sites. Our aims were to investigate in male elite swimmers the associations
      of n-6 and n-3 PUFA and alpha- and gamma-tocopherols with proxies of membrane
      stability (phase angle and erythrocyte osmotic fragility) and of PUFA in plasma
      NEFA with specific skinfolds. Brazilian male elite swimmers (n = 20) under
      regular training for an average of 4.1 h/d and 6.1 d/wk took part in the study.
      Blood samples were obtained once after 18-hour rest and an overnight fast. Fatty
      acids were determined in plasma NEFA and erythrocytes by gas chromatolography and
      tocopherols were determined in plasma and erythrocytes by high-performance liquid
      chromatography. The status of PUFA was assessed as mean melting point, PUFA index
      [(Sigman-6 + Sigman-3) / (Sigman-7 + Sigman-9)] and docosahexaenoic acid indices
      (22:5n-6/22:4n-6 and 22:6n-3/22:5n-6 ratios) calculated from erythrocyte fatty
      acids. Phase angle was associated with an index of docosahexaenoic acid
      inadequacy (22:5n-6/22:4n-6; r = -0.53, P = .019) and with 22:5n-3 in
      erythrocytes (r = 0.51, P = .024), and erythrocyte osmotic fragility was
      associated with plasma alpha-tocopherol (r = -0.51, P = .05), which is a
      biomarker of vitamin E status. Plasma NEFAs 18:3n-3 and 20:4n-6 were positively
      associated with skinfolds of the trunk and arms (r = 0.49-0.59, P = .011-.043).
      The data presented indicate that n-3 PUFA and vitamin E states possibly improve
      membrane stability in elite swimmers and that the extent of specific anatomic
      sites of subcutaneous adipose tissue in the upper body might contribute to the
      composition of NEFA in the resting state.

PMID- 19854376
TI  - Soymilk supplementation does not alter plasma markers of inflammation and
      oxidative stress in postmenopausal women.
AB  - Aging is associated with increasing levels of systemic inflammation and oxidative
      stress, both of which contribute to the progression of cardiovascular disease.
      Attenuation of such processes via dietary intervention has significant public
      health implications. Soyfoods, as a source of high-quality protein and
      isoflavones, may improve such indices, although such effects in healthy aging
      women are not well delineated. The purpose of this study was to test the
      hypothesis that 4 weeks of daily soymilk consumption would improve systemic
      markers of inflammation and oxidative stress in postmenopausal women when
      compared with a dairy control. In September 2009, a single-blind, randomized,
      controlled trial was conducted on 31 postmenopausal women at Baylor University,
      Waco, Tex. Subjects were randomly assigned to consume 3 servings of vanilla soy
      (n = 16) or reduced fat dairy (n = 15) milk per day for 4 weeks. Plasma markers
      of inflammation (tumor necrosis factor alpha [TNF-alpha], interleukin [IL]-1beta,
      IL-6) and oxidative stress (superoxide dismutase [SOD], glutathione peroxidase
      [GPx], cyclooxygenase-2 [COX-2]) were obtained before and after supplementation.
      No significant differences were observed for any of the plasma inflammatory (TNF
      alpha, P = .08; IL-1beta, P = .14; IL-6, P = .26) or oxidative stress (SOD, P =
      .68; GPx, P = .58; COX-2, P = .99) variables by dietary treatment group. Despite
      good dietary compliance, our study failed to show a significant effect of soymilk
      consumption on markers of inflammation and oxidative stress in this
      postmenopausal female population. Potential reasons for this nonsignificant
      finding are discussed, and future research directions are presented.

PMID- 19854378
TI  - Carbohydrates blended with polydextrose lower gas production and short-chain
      fatty acid production in an in vitro system.
AB  - Maximizing health benefits of prebiotics, while limiting negative side effects,
      is of importance to the food industry. This study examined several
      oligosaccharides and their blends in an in vitro fermentation model. Substrates
      included medium- and long-chain fructooligosaccharides (FOS), oligofructose
      enriched inulin, galactooligosaccharide, polydextrose (POL), and 50:50 substrate
      blends. Substrates and blends were fermented in vitro using human fecal inoculum,
      and fermentation characteristics were quantified at 0, 4, 8, and 12 hours. We
      hypothesized that mixtures of short- and long-chain oligosaccharides would
      generate less gas than do short-chain oligosaccharides and modulate gut
      microflora to a greater extent than do long-chain oligosaccharides. Carbohydrates
      blended with POL had decreased (P < .01) total gas volume and H(2) produced after
      4, 8, and 12 hours of fermentation compared with individual carbohydrates. Mixing
      of 2 oligofructose-enriched inulin products led to less (P < .05) gas produced
      and a slower (P < .05) rate of production. When mixed with POL, all carbohydrates
      tested in the present study produced less total short-chain fatty acids (P < .04)
      and butyrate (P < .0001) after 12 hours of in vitro fermentation, compared with
      individual carbohydrates. The bifidogenic effect of medium-chain FOS and
      oligofructose-enriched inulin after 12 hours of in vitro fermentation was lower
      (P < .05) when mixed with POL. Mixing the pure carbohydrates with
      galactooligosaccharide increased (P < .05) bifidobacteria counts measured after
      12 hours of in vitro fermentation, except when mixed with medium-chain FOS. In
      general, when mixed with POL, all carbohydrates had lower gas production, gas
      production rates, butyrate and total short-chain fatty acid production, and
      bifidobacteria counts than when fermented alone for 12 hours.

PMID- 19854379
TI  - Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin
      signaling pathway in rats and in COS-1 cells.
AB  - Iron deficiency (ID) is one of the most commonly known forms of nutritional
      deficiencies. Low body iron is thought to induce neurologic defects but may also
      play a protective role against cancer development by cell growth arrest. Thus, ID
      may affect cellular pathways controlling cell growth and proliferation, the
      mechanism of which is still not fully understood. The serine/threonine protein
      kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR),
      is known to play a crucial role in the regulation of cell growth and survival.
      Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three
      week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had
      free access to a control diet (C group) or an iron-deficient diet (D group). The
      third group (PF group) were pair-fed the control diet to the mean intake of the D
      group. After 4 weeks, rats were killed and their brains were sampled. In separate
      experiments, COS-1 cells were cultured with or without the iron chelator
      deferoxamine. Western blots of brain samples and COS-1 lysates were used to
      analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6
      kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models,
      we show for the first time that iron deficiency depresses Akt activity in rats
      and in COS-1 cells, leading to a decrease in mTOR activity.

PMID- 19854380
TI  - Ingestion of potato starch containing high levels of esterified phosphorus
      reduces calcium and magnesium absorption and their femoral retention in rats.
AB  - Many studies have shown that esterified phosphorus (P) in diets has a favorable
      effect on mineral absorption in humans and animals. Phosphorylated
      oligosaccharides derived from potato starch increase calcium (Ca) absorption from
      the rat intestine both in situ and in vitro. We hypothesized that the feeding of
      potato starch has a potential to increase Ca or magnesium (Mg) absorption. Male
      Sprague-Dawley rats at 7 weeks were fed 4 types of diet containing either 60%
      sucrose, cornstarch, or 1 of 2 types of potato starch with different P contents
      for 1, 3, or 5 weeks. A balance test for Ca, Mg, and P was undertaken, and these
      mineral contents in the femur were determined for the 4 diet groups at each
      feeding period in vivo. Ingestion of potato starch increased Ca, Mg, and P
      excretion into feces and decreased the absorption rate of Ca and Mg. Femoral Ca
      contents were also decreased in the rats fed the potato starch diets compared
      with those in rats fed the sucrose or cornstarch diet. In vitro experiment in Ca
      absorption was undertaken using everted jejunal and ileal sacs of the small
      intestine in male Sprague-Dawley rats (7 weeks old). The potato starch
      application did not induce significant increase in Ca absorption compared with
      nonstarch (control) or cornstarch application. In conclusion, the ingestion of
      potato starch does not increase Ca and Mg absorption and rather accelerates their
      excretion, inducing the decrease in mineral absorption and retention in growing
      rats.

PMID- 19854381
TI  - Antiobesity action of a daidzein derivative on male obese mice induced by a high
      fat diet.
AB  - Emerging evidence suggests that consumption or supplementation of foods rich in
      iso flavones may has a beneficial effect on obesity and glucose levels in animals
      and humans. It has been demonstrated that genistein, the main component of iso fl
      avones, could significantly reduce body weight and fat pad size. However, there
      is no evidence as to whether daidzein, which is also a main component of
      isoflavones, has the same effect. We hypothesize that LRXH609 (Dzd; a daidzein
      derivative) also has an antiobesity effect. In this study, we investigate the
      effects of Dzd on body weight, adipose tissue, blood, and liver lipid levels in
      obese mice fed a high-fat diet. Activities of pancreatic lipase and lipoprotein
      lipase, as well as lipolysis, were verified to clarify the potential mechanism of
      the daidzein. The results indicate that Dzd can significantly reduce body and fat
      pad weight and ameliorate the high-fat diet-induced hyperlipoidemia. We also
      found that Dzd inhibits the activity of pancreatic lipase and lipoprotein lipase
      in a dose-dependent manner, inhibits the differentiation of rat preadipocytes,
      and stimulates lipolysis by activating hormone-sensitive lipase.

PMID- 19854383
TI  - A descriptive cross-sectional study of the prevalence of 25-hydroxyvitamin D
      deficiency and association with bone markers in a hospitalized population.
AB  - Patients with gastrointestinal disease may be in particular risk of
      hypovitaminosis D because of reduced intestinal uptake or metabolism in the
      liver. The aim of the present study was to evaluate the prevalence of vitamin D
      deficiency in several groups of patients with various gastroenterologic diseases
      compared with patients without any chronic disease. We tested the hypothesis that
      persons with a gastrointestinal disease are at higher risk of hypovitaminosis D
      than persons with no chronic disease and whether this group needs special
      attention regarding their nutrition. We included patients admitted to our
      department of gastroenterology. The concentration of 25-hydroxyvitamin D
      (25(OH)D2+D3) was defined as insufficient when less than 50 nmol/L, deficient
      when less than 25 nmol/L, and severely deficient when less than 12.5 nmol/L. We
      included 146 patients with a mean age of 55 years (range, 16-93 years). 25(OH)D
      was sufficient in 47%, insufficient in 29%, deficient in 12%, and severely
      deficient in 11% of the population. Participants without chronic disease had a
      significantly higher mean level of 25(OH)D (57 nmol/L) compared to participants
      with cirrhosis (15 nmol/L, P = .002) and alcoholism (31 nmol/L, P = .003). A
      linear relationship between 25(OH)D and alkaline phosphatase could be
      demonstrated (Spearman rho, -0.299; P < .001). Participants with severe 25(OH)D
      deficiency had higher levels of total alkaline phosphatase (149.5 vs 76 U/L, P =
      .001) and parathyroid hormone (5.1 vs 2.8 pmol/L; P = .001). We recommend
      measuring the level of 25(OH)D and parathyroid hormone in patients with chronic
      diseases, especially alcoholism and cirrhosis.

PMID- 19854382
TI  - Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid
      levels in rats.
AB  - Chronic, excessive ethanol intake can increase retinoic acid (RA) catabolism by
      inducing cytochrome P450 2E1 (CYP2E1). Vitamin E (VE) is an antioxidant
      implicated in CYP2E1 inhibition. In the current study, we hypothesized that VE
      supplementation inhibits CYP2E1 and decreases RA catabolism, thereby preventing
      ethanol-induced hepatocyte hyperproliferation. For 1 month, 4 groups of Sprague
      Dawley rats were fed a Lieber-DeCarli liquid ethanol (36% of the total energy)
      diet as follows: either ethanol alone (Alc group) or ethanol in combination with
      0.1 mg/kg body weight of all-trans-RA (Alc + RA group), 2 mg/kg body weight of VE
      (Alc + VE group), or both together (Alc + RA + VE group). Control rats were pair
      fed a liquid diet with an isocaloric amount of maltodextrin instead of ethanol.
      The ethanol-fed groups had 3-fold higher hepatic CYP2E1 levels, 50% lower hepatic
      RA levels, and significantly increased hepatocyte proliferation when compared
      with the controls. The ethanol-fed rats given VE had more than 4-fold higher
      hepatic VE concentrations than the ethanol-fed rats without VE, but this did not
      prevent ethanol induction of CYP2E1, lower hepatic retinoid levels, or
      hepatocellular hyperproliferation. Furthermore, VE supplementation could not
      prevent RA catabolism in liver microsomal fractions of the ethanol-fed rats in
      vitro. These results show that VE supplementation can neither inhibit ethanol
      induced changes in RA catabolism nor prevent ethanol-induced hepatocyte
      hyperproliferation in the rat liver.

PMID- 19854384
TI  - Prevalence of vitamin K and vitamin D deficiency in patients with hepatobiliary
      and pancreatic disorders.
AB  - Little is known about the role of fat-soluble vitamins K and D in liver function
      and bone metabolism in biliary and pancreatic diseases associated with
      cholestasis and/or fat malabsorption. The aim of this study was to determine
      vitamin K of bone, vitamin D and parathyroid hormone status in patients with
      biliary and pancreatic disorders. In 90 consecutive patients (mean +/- SD age,
      65.5 +/- 17.7 years; 45 females) undergoing endoscopic retrograde
      cholangiopancreatography (68 with choledocholithiasis, 14 with other benign
      condition, and 8 with cholangiopancreatic cancers) fasting concentrations of
      carboxylated (cOC) and undercarboxylated osteocalcin (ucOC), 25-hydroxyvitamin D,
      calcium, phosphorus, magnesium, prothrombin time, liver function tests, lipase,
      and creatinine were measured. Vitamin D deficiency (25-hydroxyvitamin D <50
      nmol/L) was found in 45.6% of patients and elevated parathyroid hormone levels in
      27.8%. The ratio ucOC/cOC (index of vitamin K deficiency) was above 20% in 50.6%
      of patients, above 30% in 31%, and above 50% in 18.4%. Hyperbilirubinemia was a
      significant independent predictor of low cOC (odds ratio [OR], 11.6; 95%
      confidence interval [CI], 1.9-59.4; P = .07). The ratio ucOC/cOC positively
      correlated with alanine aminotransferase levels (r = 0.410; P < .001). Elevated
      gamma-glutamyltransferase (>180 U/L) and international normalized ratio (>1.1)
      levels were significant independent predictors of ucOC/cOC greater than 30% after
      adjustment for other covariants (OR, 5.5; 95% CI, 1.2-25.2; P = .027, and OR,
      3.1; 95% CI, 1.1-8.8; P = .036, respectively). This study demonstrates that
      vitamin K and vitamin D deficiencies are common in patients undergoing endoscopic
      retrograde cholangiopancreatography. Liver dysfunction is associated with and
      predictive of vitamin K deficiency of bone and decreased production of
      osteocalcin, indicating the need for appropriate supplementation.

PMID- 19854385
TI  - The use of 4DCT to reduce lung dose: a dosimetric analysis.
AB  - Dosimetric studies on respiratory movement suggest several advantages toward the
      use of 4-dimensional computed tomography (4DCT) in radiation treatment planning.
      4DCT is a method to obtain a series of CT scans each representing a different
      respiratory phase. The use of 4DCT has provided substantial information on tumor
      movement in the lung, allowing for the creation of custom planning margins
      explicitly including respiratory motion. These custom motion margins may result
      in an increase in the amount of normal lung in the field; however, it is believed
      less normal lung is irradiated than if generic motion margins were used. Clinical
      data regarding dose to normal lung by using 4DCT remain rather limited. Thus, a
      study presenting figures on the change in normal lung dose between planned free
      breathing CT and 4DCT cases would be useful to the dosimetry community. We have
      generated plans comparing fast spiral CT and 4DCT in regard to tumor coverage and
      the resulting dose to normal lung for the clinical target volume (CTV) and
      planning target volume (PTV) expansions used at our institution. These data were
      analyzed for free breathing and 4D plans of 6 lung cancer patients using
      intensity modulated radiation therapy (IMRT). We compared doses to normal lung
      tissue between free breathing and 4DCT plans.

PMID- 19854387
TI  - Cord dose specification and validation for stereotactic body radiosurgery of
      spine.
AB  - Effective dose to a portion of the spinal cord in treatment segment, rather than
      the maximum point dose in the cord surface, was set as the dose limit in
      stereotactic-body radiosurgery (SBRS) of spine. Such a cord dose specification is
      sensitive to the volume size and position errors. Thus, we used stereotactic
      image guidance to minimize phantom positioning errors and compared the results of
      a 0.6-cm(3) Farmer ionization chamber and a 0.01-cm(3) compact ionization chamber
      to determine the detector size effect on 9 SBRS cases. The experimental errors
      ranging from 2% to 7% were estimated by the deviation of the mean dose in plans
      to the chamber with spatial displacements of 0.5 mm. The mean and measured doses
      for the large chamber to individual cases were significantly (approximately 17%)
      higher than the doses with the compact chamber placed at the same point. Our
      experimental results shown that the mean doses to the volume of interest could
      represent the measured cord doses. For the 9 patients, the mean doses to 10% of
      the cord were about 10 Gy, while the maximum cord doses varied from 11.6 to 17.6
      Gy. The mean dose, possibly correlated with the cord complication, provided us an
      alternative and reliable cord dose specification in SBRS of spine.

PMID- 19854386
TI  - Obtaining normal tissue constraints using intensity modulated radiotherapy (IMRT)
      in patients with oral cavity, oropharyngeal, and laryngeal carcinoma.
AB  - The purpose of this study was to evaluate normal tissue dose constraints while
      maintaining planning target volume (PTV) prescription without reducing PTV
      margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with
      oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma
      (group III) were reviewed. Parotid constraints were a mean dose to either parotid
      < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid <
      20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with
      simultaneous integrated boost (SIB). All patients met constraints for cord and
      brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients
      with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy
      (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal
      patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was
      the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively).
      PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%,
      and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean
      parotid dose of 26 Gy was met 40% of the time. However, a combination of
      constraints allowed for sparing of the parotid based on different criteria and
      was met in high numbers. This was accomplished without reducing PTV-parotid
      overlap. What dose constraint best correlates with subjective and objective
      functional outcomes remains a focus for future study.

PMID- 19854388
TI  - Online kidney position verification using non-contrast radiographs on a linear
      accelerator with on board KV X-Ray imaging capability.
AB  - The kidneys are dose-limiting organs in abdominal radiotherapy. Kilovoltage (kV)
      radiographs can be acquired using on-board imager (OBI)-equipped linear
      accelerators with better soft tissue contrast and lower radiation doses than
      conventional portal imaging. A feasibility study was conducted to test the
      suitability of anterior-posterior (AP) non-contrast kV radiographs acquired at
      treatment time for online kidney position verification. Anthropomorphic phantoms
      were used to evaluate image quality and radiation dose. Institutional Review
      Board approval was given for a pilot study that enrolled 5 adults and 5 children.
      Customized digitally reconstructed radiographs (DRRs) were generated to provide a
      priori information on kidney shape and position. Radiotherapy treatment staff
      performed online evaluation of kidney visibility on OBI radiographs. Kidney dose
      measured in a pediatric anthropomorphic phantom was 0.1 cGy for kV imaging and
      1.7 cGy for MV imaging. Kidneys were rated as well visualized in 60% of patients
      (90% confidence interval, 34-81%). The likelihood of visualization appears to be
      influenced by the relative AP separation of the abdomen and kidneys, the axial
      profile of the kidneys, and their relative contrast with surrounding structures.
      Online verification of kidney position using AP non-contrast kV radiographs on an
      OBI-equipped linear accelerator appears feasible for patients with suitable
      abdominal anatomy. Kidney position information provided is limited to 2
      dimensional "snapshots," but this is adequate in some clinical situations and
      potentially advantageous in respiratory-correlated treatments. Successful
      clinical implementation requires customized partial DRRs, appropriate imaging
      parameters, and credentialing of treatment staff.

PMID- 19854389
TI  - IMRT in a pregnant patient: how to reduce the fetal dose?
AB  - The purpose of our study was to find a solution for fetal dose reduction during
      head-and-neck intensity modulated radiation therapy (IMRT) of a pregnant patient.
      The first step was optimization of the IMRT treatment plan with as few monitor
      units (MUs) as possible, while maintaining an acceptable dose distribution. The
      peripheral dose originating from the final IMRT plan was measured at distances
      reaching from the most proximal to the most distal fetal position, along the
      accelerator's longitudinal axis, using an anthropomorphic phantom extended with
      water-equivalent plastic. The measured peripheral dose was divided into leakage,
      and internal and collimator scatter, to find the degree to which each component
      influences the peripheral dose to build an appropriate shield. Collimator scatter
      was the greatest contributor to the peripheral dose throughout the range of the
      growing fetus. A shield was built and placed beneath the accelerator head,
      extending caudally from the field edge, to function as an extra collimator jaw.
      This shield reduced the fetal dose by a factor of 3.5. The peripheral dose
      components were also measured for simple rectangular fields and also here the
      collimator scatter was the greatest contributor to the peripheral dose.
      Therefore, the shielding used for the IMRT treatment of our patient could also be
      used when shielding in conventional radiotherapy. It is important for a radiation
      therapy department to be prepared for treatment of a pregnant patient to shield
      the fetus efficiently.

PMID- 19854390
TI  - The effect of oblique electron beams to the surface dose under the bolus.
AB  - The aim of this study is to determine the effect of bolus to the surface dose in
      oblique electron incidences. Irradiations with 4.5, 6, 7.5, 9, and 12-MeV
      electron beams were made for the incidence angles of 0 degrees, 15 degrees, 30
      degrees, 45 degrees, 60 degrees, 75 degrees and using 3 different bolus setups:
      (1) unbolused (no bolus), (2) 5-mm bolus, and (3) 10-mm bolus. A set of EBT
      gafchromic film pieces placed on the phantom surface was irradiated with a 400
      cGy dose at D(max) for each setup. Whereas surface dose increased with increasing
      incidence degrees in the absence of a bolus, it was seen that there was a large
      surface dose decreasing in the presence of a bolus with increasing incidence
      angles. For 60 degrees incidence angle, the relative surface doses with unbolused
      setup were: 88.10%, 90.06%, 89.35%, 90.25%, and 97.10%; with 5-mm bolus: 66.45%,
      81.20%, 99.78%, 124.43%, and 116.07%; and with 10-mm bolus: 22.65%, 45.20%,
      55.20%, 65.82%, and 90.27% for 4.5, 6, 7.5, 9, and 12 MeV, respectively. The use
      of bolus in the treatment of highly oblique surfaces with low-energy electron
      beams significantly decreases the surface dose.

PMID- 19854391
TI  - Evaluation of four volume-based image registration algorithms.
AB  - We evaluated 4 volume-based automatic image registration algorithms from 2
      commercially available treatment planning systems (Philips Syntegra and
      BrainScan). The algorithms based on cross correlation (CC), local correlation
      (LC), normalized mutual information (NMI), and BrainScan mutual information
      (BSMI) were evaluated with: (1) the synthetic computed tomography (CT) images,
      (2) the CT and magnetic resonance (MR) phantom images, and (3) the CT and MR head
      image pairs from 12 patients with brain tumors. For the synthetic images, the
      registration results were compared with known transformation parameters, and all
      algorithms achieved accuracy of submillimeter in translation and subdegree in
      rotation. For the phantom images, the registration results were compared with
      those provided by frame and marker-based manual registration. For the patient
      images, the results were compared with anatomical landmark-based manual
      registration to qualitatively determine how the results were close to a
      clinically acceptable registration. NMI and LC outperformed CC and BSMI, with the
      sense of being closer to a clinically acceptable result. As for the robustness,
      NMI and BSMI outperformed CC and LC. A guideline of image registration in our
      institution was given, and final visual assessment is necessary to guarantee
      reasonable results.

PMID- 19854392
TI  - Single port laparoscopic cholecystectomy in adults and children: tools and
      techniques.

PMID- 19854393
TI  - Predicted risk of mortality models: surgeons need to understand limitations of
      the University HealthSystem Consortium models.
AB  - BACKGROUND: The University HealthSystem Consortium (UHC) mortality risk
      adjustment models are increasingly being used as benchmarks for quality
      assessment. But these administrative database models may include postoperative
      complications in their adjustments for preoperative risk. The purpose of this
      study was to compare the performance of the UHC with the Society of Thoracic
      Surgeons (STS) risk-adjusted mortality models for adult cardiac surgery and
      evaluate the contribution of postoperative complications on model performance.
      STUDY DESIGN: We identified adult cardiac surgery patients with mortality risk
      estimates in both the UHC and Society of Thoracic Surgeons databases. We compared
      the predictive performance and calibration of estimates from both models. We then
      reestimated both models using only patients without any postoperative
      complications to determine the relative contribution of adjustments for
      postoperative events on model performance. RESULTS: In the study population of
      2,171 patients, the UHC model explained more variability (27% versus 13%, p <
      0.001) and achieved better discrimination (C statistic = 0.88 versus 0.81, p <
      0.001). But when applied in the population of patients without complications, the
      UHC model performance declined severely. The C statistic decreased from 0.88 to
      0.49, a level of discrimination equivalent to random chance. The discrimination
      of the Society of Thoracic Surgeons model was unchanged (C statistic of 0.79
      versus 0.81). CONCLUSIONS: Although the UHC model demonstrated better performance
      in the total study population, this difference in performance reflects
      adjustments for conditions that are postoperative complications. The current UHC
      models should not be used for quality benchmarks.

PMID- 19854394
TI  - Variability in reoperation rates at 182 hospitals: a potential target for quality
      improvement.
AB  - BACKGROUND: Reoperation rate has gained increasing attention as a potential
      indicator of surgical quality. Objectives of this study were to examine the
      feasibility of assessing reoperation rates at 182 hospitals to identify
      institutions with outlying performance, to examine potentially modifiable factors
      that are associated with reoperations, and to determine if a more parsimonious
      logistic regression model effectively predicts reoperations. STUDY DESIGN:
      Patients were identified who underwent colorectal procedures at 182 hospitals
      participating in the American College of Surgeon's National Surgical Quality
      Improvement Program in 2006-2007. Risk-adjusted regression models for reoperation
      were developed to identify hospitals that had ratios of observed-to-expected
      events that were substantial outliers. RESULTS: Of 23,098 patients identified,
      1,320 (5.7%) required reoperations. Reoperation occurred significantly more often
      than expected in 16 hospitals and less often than expected in 7 hospitals (p <
      0.05). Factors that were associated with an increased risk of reoperation were
      advanced American Society of Anesthesiologists class, male gender, contaminated
      wounds, surgical extent, surgical indication, smoking, poor functional status,
      disseminated cancer, COPD, steroid dependence, anemia, body mass index
      (calculated as kg/m(2)) >35 or < or = 18.5, and hypertension. Compared with the
      full logistic regression model, there was a high degree of correlation with the
      more parsimonious logistic model containing only the first six variables (r =
      0.996). CONCLUSIONS: There is considerable variability in reoperation rates at
      American College of Surgeon's National Surgical Quality Improvement Program
      hospitals. American College of Surgeon's National Surgical Quality Improvement
      Program data can be used to provide individual hospitals with risk-adjusted self
      assessment data on reoperations to potentially identify quality-improvement
      opportunities.

PMID- 19854395
TI  - Quality of reporting in randomized trials published in high-quality surgical
      journals.
AB  - BACKGROUND: Randomized controlled trials (RCTs) in surgery can provide valuable
      evidence of the efficacy of interventions if they are well-designed,
      appropriately executed, and adequately reported. Adequate reporting of
      methodology in surgical RCTs is known to be poor, and adverse-event reporting in
      surgical research is inconsistent. The Consolidated Standards of Reporting Trials
      (CONSORT) statement is a framework to help authors report their findings in a
      transparent manner. Extensions to the CONSORT statement have been published
      recently to address deficiencies in adverse-event reporting and in reporting of
      specific criteria related to nonpharmacologic treatments. The aim of this study
      was to assess the quality of reporting of trial methodology and adverse events in
      a sample of general surgical RCTs published in high-quality surgical journals
      using the criteria specified in the CONSORT statements. STUDY DESIGN: We used
      impact factor to identify the top three ranked surgical journals in 2004. We then
      obtained information on all RCTs published in these journals in the 2005 calendar
      year. We assessed quality of reporting using Jadad score, compared the quality of
      RCTs from CONSORT-endorsing journals with nonendorsers, and assessed the number
      of RCTs adequately reporting key generic methodologic, adverse-event-related, and
      specific nonpharmacologic criteria. RESULTS: Of 42 RCTs analyzed, only 40% (17 of
      42) had a Jadad score > or = 3. There was no significant difference in the number
      of high-quality RCTs published in CONSORT-endorsing journals compared with
      nonendorsers (p = 0.3). The median percentage of RCTs adequately reporting
      generic methodologic, adverse-event-related, and specific nonpharmacologic
      criteria was 32.5%, 17%, and 36.5%, respectively. CONCLUSIONS: Quality of
      reporting of generic methodologic, adverse-event-related, and specific
      nonpharmacologic criteria in surgical RCTs is poor. Increased attention to
      quality of reporting of surgical RCTs is required if studies are to meet
      published criteria.

PMID- 19854396
TI  - A multiple imputation model for imputing missing physiologic data in the national
      trauma data bank.
AB  - BACKGROUND: Like most trauma registries, the National Trauma Data Bank (NTDB) is
      limited by the problem of missing physiologic data. Multiple imputation (MI) has
      been proposed to simulate missing Glasgow Coma Scale (GCS) scores, respiratory
      rate (RR), and systolic blood pressure (SBP). The aim of this study was to
      develop an MI model for missing physiologic data in the NTDB and to provide
      guidelines for its implementation. STUDY DESIGN: The NTDB 7.0 was restricted to
      patients admitted in 2005 with at least one anatomic injury code. A series of
      auxiliary variables thought to offer information for the imputation process was
      selected from the NTDB by literature review and expert opinion. The relation of
      these variables to physiologic variables and to the fact that they were missing
      was examined using logistic regression. The MI model included all auxiliary
      variables that had a statistically significant association with physiologic
      variables or with the fact that they were missing (Bonferroni-corrected p value
      <0.05). RESULTS: The NTDB sample included 373,243 observations. Glasgow Coma
      Scale, respiratory rate, and systolic blood pressure were missing for 20.3%,
      3.9%, and 8.5% of data observations, respectively. The MI model included
      information on the following: gender, age, anatomic injury severity, transfer
      status, injury mechanism, intubation status, alcohol and drug test results,
      emergency department disposition, total length of stay, ICU length of stay,
      duration of mechanical ventilation, and discharge disposition. The MI model
      offered good discrimination for predicting the value of physiologic variables and
      the fact that they were missing (areas under the receiver operating
      characteristic curve between 0.832 and 0.999). CONCLUSIONS: This article proposes
      an MI model for imputing missing physiologic data in the NTDB and provides
      guidelines to facilitate its use. Implementation of the model should improve the
      quality of research involving the NTDB. The methodology can also be adapted to
      other trauma registries.

PMID- 19854397
TI  - Impact of hypothermia (below 36 degrees C) in the rural trauma patient.
AB  - BACKGROUND: Hypothermia is an independent predictor of mortality based on urban
      studies. But this association has not been described in the rural setting. This
      study's purpose was to evaluate hypothermia as a cofactor to mortality,
      complications, and hospital length of stay (LOS) parameters in the rural trauma
      setting. STUDY DESIGN: The National Trauma Registry of the American College of
      Surgeons database for our rural, Level I trauma center was queried for a 5-year
      period (July 2002 to June 2007) to identify adult trauma patients. Multivariate
      regression models were used to evaluate the association of hypothermia with
      mortality; infectious complications; organ dysfunction; and, among survivors,
      hospital LOS parameters. RESULTS: Of 9,482 adult patients admitted, 1,490 (15.7%)
      patients were hypothermic. Hypothermia had an adjusted odds ratio of 1.70 for
      mortality (95% CI, 1.35 to 2.12; p < 0.001). After controlling for covariates,
      hypothermia was not significantly associated with infectious complications or
      organ dysfunction, except for arrhythmia (adjusted odds ratio, 1.40; CI, 1.03 to
      1.90; p = 0.031). Hypothermia was not associated with a difference in ICU (p =
      0.310) or ventilator (p = 0.144) LOS. But a slight increase in hospital days was
      noted in the hypothermic patient (hazards ratio, 0.890 for discharge; 95% CI,
      0.838 to 0.946; p < 0.001). CONCLUSIONS: Hypothermia is a common problem at
      admission in a rural trauma center. It is associated with an increase in
      hospitalized days but not with increased ICU or ventilator days among survivors.
      Other than arrhythmias, it was not significantly associated with other National
      Trauma Registry of the American College of Surgeons infectious or organ
      dysfunction complications. Hypothermia is an independent risk factor for
      mortality in the rural trauma patient.

PMID- 19854398
TI  - Fondaparinux for prevention of venous thromboembolism in high-risk trauma
      patients: a pilot study.
AB  - BACKGROUND: Venous thromboembolic events (VTE) remain a major cause of morbidity
      and mortality after trauma. Fondaparinux, a synthetic, nonheparin drug, has shown
      promise in reducing VTE in orthopaedic patients, but has not previously been
      studied in trauma patients. The goal of this study was to determine the safety
      and efficacy of fondaparinux when incorporated into our VTE prevention protocol.
      We hypothesized that the occult deep vein thrombosis (DVT) rate in high-risk
      patients receiving fondaparinux would be <5%. STUDY DESIGN: Consented patients
      were assigned to a treatment group stratified by their VTE risk factors: high
      risk, fondaparinux 2.5 mg subcutaneously once daily; very high-risk, both
      fondaparinux and pneumatic compression. Patients who were not candidates for
      anticoagulation received pneumatic compression only. All patients underwent
      surveillance venous ultrasonography imaging of upper and lower extremities on
      enrollment and weekly thereafter. Serum samples were analyzed for peak and trough
      drug concentration levels. RESULTS: Overall incidence of DVT among the 87
      enrolled patients was 4.6%. DVT developed in only 1 of 80 patients who received
      fondaparinux (1.2%). One patient assigned to fondaparinux had a DVT on initial
      scan before receiving prophylaxis. DVT developed in two of six patients in
      pneumatic compression only (33%). There were no episodes of pulmonary embolism,
      thrombocytopenia, or bleeding attributable to fondaparinux. Serum levels
      indicated adequate absorption of the drug and an effective dosing regimen.
      CONCLUSIONS: Fondaparinux appears to offer protection against VTE in high-risk
      trauma patients. Its once-daily dosing regimen can improve compliance and reduce
      cost and eliminate risk of heparin-induced thrombocytopenia.

PMID- 19854399
TI  - Complication rates among trauma centers.
AB  - BACKGROUND: The goal of this study was to examine the association between patient
      complications and admission to Level I trauma centers (TC) compared with
      nontrauma centers (NTC). STUDY DESIGN: This was a retrospective cohort study of
      data derived from the National Study on the Costs and Outcomes of Trauma (NSCOT).
      Patients were recruited from 18 Level I TCs and 51 NTCs in 15 regions
      encompassing 14 states. Trained study nurses, using standardized forms,
      abstracted the medical records of the patients. The overall number of
      complications per patient was identified, as was the presence or absence of 13
      specific complications. RESULTS: Patients treated in TCs were more likely to have
      any complication compared with patients in NTCs, with an adjusted relative risk
      (RR) of 1.34 (95% CI, 1.03, 1.74). For individual complications, only the urinary
      tract infection RR of 1.94 (95% CI, 1.07, 3.17) was significantly higher in TCs.
      TC patients were more likely to have 3 or more complications (RR, 1.83; 95% CI,
      1.16, 2.90). Treatment variables that are surrogates for markers of injury
      severity, such as use of pulmonary artery catheters, multiple operations, massive
      transfusions (> 2,500 mL packed red blood cells), and invasive brain catheters,
      occurred significantly more often in TCs. CONCLUSIONS: Trauma centers have a
      slightly higher incidence rate of complications, even after adjusting for patient
      case mix. Aggressive treatment may account for a significant portion of TC
      associated complications. Pulmonary artery catheter use and intubation had the
      most influence on overall TC complication rates. Additional study is needed to
      provide accurate benchmark measures of complication rates and to determine their
      causes.

PMID- 19854400
TI  - Timing of breast cancer treatments with oocyte retrieval and embryo
      cryopreservation.
AB  - BACKGROUND: Protecting future childbearing motivates young women with breast
      cancer to seek oocyte or embryo cryopreservation. Concerns about delays in cancer
      treatment may influence patients and practitioners considering these procedures.
      In this study, we compared timing of chemotherapy in women who underwent ovarian
      stimulation/oocyte retrieval (OR) and embryo cryopreservation with those who did
      not. STUDY DESIGN: Eighty-two women younger than 40 years of age, who received
      adjuvant chemotherapy for breast cancer, were retrospectively identified.
      Nineteen underwent OR and 63 did not (CON). The timing of OR, surgery, and
      chemotherapy were compared with the time intervals between diagnosis and
      treatments in the CON group. RESULTS: The mean ages of women were 33.7 years (OR
      group) and 35.2 years (CON group); 84.2% of OR and 25.4% of CON were nulliparous.
      The median time from initial diagnosis to reproductive endocrinology consultation
      was 30.1 days (range 4 to 133 days) and from referral to OR was 32 days (range 13
      to 66 days). The median times from initial diagnosis to chemotherapy in OR versus
      CON groups were 71 days (range 45 to 161 days) and 67 days (range 27 to 144
      days), respectively, p < 0.27. The median time interval from definitive operation
      to chemotherapy was similar in the two groups: 30 days (OR; range 14 to 100 days)
      and 29 days (CON; range 12 to 120 days), p < 0.79. CONCLUSIONS: Fertility
      preservation is an important component of quality of life for young women with
      breast cancer. The time investment required for OR and cryopreservation is
      manageable and does not significantly prolong the time interval from diagnosis to
      start of adjuvant chemotherapy.

PMID- 19854401
TI  - Attaining negative margins in breast-conservation operations: is there a
      consensus among breast surgeons?
AB  - BACKGROUND: The purpose of this survey was to ascertain the most common surgical
      practices for attaining negative (tumor-free) surgical margins in patients
      desiring breast-conservation treatment for breast cancer to see if a consensus
      exists for optimal treatment of patients. STUDY DESIGN: We sent a survey to 1,000
      surgeons interested in the treatment of breast cancer. Three hundred eighty-one
      surgeons responded to this survey and 351 were used for the analysis (response
      rate of 38%). RESULTS: Answers showed a large variety in clinical practices among
      breast surgeons across the country. There was little intraoperative margin
      analysis; only 48% of surgeons examine the margins grossly with a pathologist and
      even fewer used frozen sections or imprint cytology. Decisions to reexcise
      specific margins varied greatly. For example, 57% of surgeons would never
      reexcise for a positive deep margin, but 53% would always reexcise for a positive
      anterior margin. Most importantly, there was a large range in answers about
      acceptable margins with ductal carcinoma in situ and invasive carcinoma. Fifteen
      percent of surgeons would accept any negative margin, 28% would accept a 1-mm
      negative margin, 50% would accept a 2-mm negative margin, 12% would accept a 5-mm
      negative margin, and 3% would accept a 10-mm negative margin. CONCLUSIONS:
      Results of this survey highlight the wide variety of practice patterns in the US
      for handling surgical margins in breast-conservation treatment. This issue
      remains controversial, with no prevailing standard of care. Consequently,
      additional study is needed in the modern era of multimodality treatment to
      examine the minimal amount of surgical treatment necessary, in conjunction with
      chemotherapy and radiation, to attain adequate local control rates in breast
      conservation treatment.

PMID- 19854403
TI  - Video self-assessment augments development of videoscopic suturing skill.
AB  - BACKGROUND: Development of surgical skills on inanimate models has been
      popularized by efforts to improve patient safety and efficiency of resident
      training. We evaluated whether surgical residents' acquisition of videoscopic
      suturing skill is accelerated by reviewing video of their own previous practice
      session. STUDY DESIGN: Fourteen residents from two general surgery training
      programs received didactic instruction on laparoscopy. Attempts at suturing and
      knotting were then timed and recorded for each subject, and half of them were
      provided a video of their attempts to review. After 7 to 10 days, repeat attempts
      were timed and recorded. Knots were mechanically tested, and videos were reviewed
      in blinded fashion. RESULTS: Baseline characteristics were similar between the
      two groups. Both groups demonstrated improvement of videoscopic suturing
      efficiency and quality. On a 27-point scale, suturing and knot quality scores
      improved by an average of 11.6 (SD 3.9) in the video review group and 2.3 (SD
      6.0) in the control group (p = 0.007). Times to complete the tasks were reduced
      by 30.3% (SD 11%) in the video review group and 3.1% (SD 32%) in the control
      group (p = 0.075). Eighty-six percent of video review subjects found the videos
      useful, and 86% of control subjects believed that videos would have been useful.
      CONCLUSIONS: Development of videoscopic suturing skill is augmented by
      independent review of earlier attempts. Knot quality and technique are improved,
      with a trend toward increased speed. This minimal-cost method of enhancing skill
      training for junior residents parallels the effectiveness of video review in
      fields such as aviation and athletics.

PMID- 19854402
TI  - Clinical significance of frozen section analysis during resection of intraductal
      papillary mucinous neoplasm: should a positive pancreatic margin for adenoma or
      borderline lesion be resected additionally?
AB  - BACKGROUND: The clinical significance of a positive intraoperative frozen section
      analysis of the pancreatic margin, especially for adenoma or borderline lesion,
      is not well understood during operations for intraductal papillary mucinous
      neoplasm of the pancreas. STUDY DESIGN: Data from 130 consecutive patients who
      underwent intraductal papillary mucinous neoplasm resection in a single
      institution were retrospectively analyzed. RESULTS: In the first intraoperative
      frozen section analysis, 26 patients were positive for adenoma or borderline
      lesion, 10 for carcinoma in situ, 2 for cancer cells floating in the duct, and 6
      for invasive cancer. Twenty-nine patients underwent additional resection, and 105
      patients finally achieved a negative pancreatic margin. Among 18 patients with a
      positive pancreatic margin for adenoma or borderline lesion, only 1 had a
      recurrence. All 20 patients who suffered a recurrence harbored invasive
      intraductal papillary mucinous carcinoma in resected specimens. In multivariate
      analysis, predictive factors of recurrence after intraductal papillary mucinous
      carcinoma resection were the presence of lymph node metastasis, serosal invasion,
      and a high level of serum carbohydrate antigen 19-9. CONCLUSIONS: The presence of
      adenoma or borderline lesion at the pancreatic margin does not always warrant
      further resection because of the low recurrence rate in the remnant pancreas.
      Recurrence after intraductal papillary mucinous neoplasm resection is influenced
      primarily by the presence and extent of invasive cancer rather than the status of
      the pancreatic margin.

PMID- 19854404
TI  - Pretraining on Southwestern stations decreases training time and cost for
      proficiency-based fundamentals of laparoscopic surgery training.
AB  - BACKGROUND: We previously reported a proficiency-based Fundamentals of
      Laparoscopic Surgery (FLS) curriculum that uniformly resulted in passing the
      technical skills certification criteria. We hypothesized that pretraining using
      the Southwestern (SW) videotrainer stations would decrease costs and training
      time and maintain benefits. STUDY DESIGN: Group I (2nd-year medical student, n =
      10) underwent FLS pretesting (Pretest 1), SW station proficiency-based training,
      repeat FLS testing (Pretest 2), FLS proficiency-based training, and final FLS
      testing (Posttest). These data were compared with a historic control, group II
      (2nd-year medical student, n = 10), which underwent FLS pretesting (Pretest 1),
      proficiency-based training, and final FLS testing (Posttest). RESULTS: During
      training, group I achieved proficiency (85.4 + or - 26.2 repetitions) for all SW
      tasks. For both groups, proficiency was achieved for 96% of the FLS tasks, with
      substantial differences detected for group I and group II repetitions (100.5 + or
      - 15.9 versus 114 + or - 25.5) and training time (6.0 + or - 1.5 versus 9.2 + or 
      2.2 hours), respectively. Per-person material costs were considerably different
      for groups I and II ($827 + or - 116 versus $1,108 + or - 393). Group I
      demonstrated significant improvement from Pretest 1 (149 + or - 39; 0% FLS pass
      rate) to Pretest 2 (293 + or - 83; p < 0.001; 60% FLS pass rate), and to Posttest
      (444 + or - 60; p < 0.001; 100% FLS pass rate). Group II demonstrated significant
      improvement from Pretest 1 (158 + or - 78; 0% FLS pass rate) to Posttest (469.7 +
      or - 12.0; p < 0.001; 100% FLS pass rate). CONCLUSIONS: Pretraining on SW
      stations decreases training time for FLS skill acquisition and maintains
      educational benefits. This strategy decreases costs associated with using
      consumable materials for training.

PMID- 19854405
TI  - Single-incision laparoscopic cholecystectomy using conventional instruments:
      early experience in comparison with the gold standard.
AB  - BACKGROUND: The aim of this pilot study was to describe our initial experience
      with single-incision laparoscopic cholecystectomy (SILC) using conventional
      laparoscopic equipment in comparison with concurrent patients undergoing
      conventional multiincision laparoscopic cholecystectomy. STUDY DESIGN: During the
      7-month study period, data from all consecutive patients undergoing SILC by two
      surgeons were retrospectively analyzed and compared with data from patients
      undergoing conventional laparoscopic cholecystectomy by the same surgeons during
      the same time period. Outcomes measures included completion rate of attempted
      SILC, operative time, length of hospital stay, postoperative pain, and assessment
      of complications. RESULTS: From 51 laparoscopic cholecystectomies performed
      during the study period, 29 were attempted using single-incision technique and 22
      were performed using the conventional four incisions. Of the attempted SILC
      cases, 14 (48%) were successfully completed, with the remainder requiring one to
      three additional skin incisions. There were no conversions to open in either
      group. Operative time was significantly longer in SILC cases compared with
      conventional laparoscopic cholecystectomy (85 versus 67 minutes; p = 0.01). There
      was a tendency toward greater postoperative pain in the SILC group. No
      substantial difference in complications was identified. CONCLUSIONS: SILC using
      conventional laparoscopic instrumentation is an effective alternative to standard
      four-incision laparoscopic cholecystectomy in selected patients. Development of a
      standardized technique and additional experience is needed for more consistent
      success. Additional studies of SILC are needed to demonstrate safety, define
      selection criteria, and determine any benefits over conventional laparoscopic
      cholecystectomy.

PMID- 19854406
TI  - Laparoscopic adjustable gastric banding for morbidly obese adolescents affects
      android fat loss, resolution of comorbidities, and improved metabolic status.
AB  - BACKGROUND: The distribution of weight loss and its impact on metabolic health
      has not been documented for laparoscopic adjustable gastric banding (LAGB) in the
      adolescent population. We hypothesized that LAGB in obese adolescents would
      result in loss of android fat mass, resolution of comorbidities, and improvement
      in metabolic status. STUDY DESIGN: Adolescents ages 14 to 17 who met criteria for
      bariatric surgery were enrolled in our FDA-approved LAGB trial. Demographic data,
      body mass index, body composition and bone density, laboratory evaluations, and
      comorbid conditions were assessed pre- and postoperatively. RESULTS: Forty-five
      patients had complete 1-year followup and 41 patients had complete 2-year
      followup. Mean preoperative weight was 299 + or - 57 lb and body mass index was
      48 + or - 6.4 kg/m(2). The percent excess weight losses at 6 months, 1 year, and
      2 years were 31 + or - 16, 46 + or - 21, and 47 + or - 22, respectively. At 1
      year followup, patients after LAGB had a significant decrease in their total and
      android fat mass. In addition, 47 of 85 identified comorbidities (55%) were
      completely resolved and 25 (29%) were improved in comparison with baseline.
      Improvements in alkaline phosphatase, aspartate aminotransferase, alanine
      aminotransferase, hemoglobin A1c, fasting insulin, triglycerides, and high
      density lipoprotein, were also seen. CONCLUSIONS: The percent excess weight loss
      after LAGB in morbidly obese adolescents is approximately 45% at 1- and 2-year
      followup, with the majority of weight loss consisting of android fat mass.
      Resolution or improvement of comorbidities is seen, and improved metabolic
      status, as demonstrated by liver function tests, lipid levels, and measures of
      glucose homeostasis, may be expected. These data support LAGB as an appropriate
      surgical option for morbidly obese adolescents.

PMID- 19854407
TI  - Gastrointestinal malignancies: when does race matter?
AB  - BACKGROUND: African Americans have a poorer survival from gastrointestinal
      cancers. We hypothesized that socioeconomic status may explain much of this
      disparity. STUDY DESIGN: Four years of population-based Medicare and Medicaid
      administrative claims files were merged with the Michigan Tumor Registry. Data
      were identified for 18,260 patients with colorectal (n = 13,001), pancreatic (n =
      2,427), gastric (n = 1,739), and esophageal (n = 1,093) cancer. Three outcomes
      were studied: the likelihood of late stage diagnosis, the likelihood of surgery
      after diagnosis, and survival. Bivariate analysis was used to compare stage and
      operation between African-American and Caucasian patients. Cox proportional
      hazard models were used to evaluate differences in survival. Statistical
      significance was defined as p < 0.05. RESULTS: In unadjusted analyses, relative
      to Caucasian patients, African-American patients with colorectal and esophageal
      cancer were more likely to present with metastatic disease, were less likely to
      have surgery, and were less likely to survive during the study period (p < 0.05).
      In a multivariate analysis, African-American patients had a higher likelihood of
      death from colorectal cancer than Caucasian patients. This difference, however,
      did not persist when late stage and surgery were taken into account (hazard ratio
      = 1.15, 95% CI = 1.06 to 1.24). No racial differences in survival were observed
      among patients with esophagus, gastric, or pancreatic cancer. CONCLUSIONS: These
      data suggest that improvements in screening and rates of operation may reduce
      differences in colorectal cancer outcomes between African-American and Caucasian
      patients. But race has little influence on survival of patients with pancreatic,
      esophageal, or gastric cancer.

PMID- 19854408
TI  - Management of recurrent inguinal hernias.

PMID- 19854409
TI  - The "off-label" role of recombinant factor VIIa in surgery: is the problem
      deficient evidence or defective concept?

PMID- 19854410
TI  - Results from the cognitive changes and retirement among senior surgeons self
      report survey.
AB  - BACKGROUND: The Cognitive Changes and Retirement among Senior Surgeons (CCRASS)
      study suggested that although subjective cognitive awareness may play a role in
      surgeons' retirement decisions, self-perceived cognitive decline did not predict
      objective cognitive performance. This article summarizes results from all
      participants who completed the survey portion of the CCRASS study. STUDY DESIGN:
      A survey examining subjective cognitive changes, changes in caseload, involvement
      in new technology, and retirement decisions, was administered to 995 surgeons at
      annual meetings of the Clinical Congress of the American College of Surgeons
      between 2001 and 2006. RESULTS: Forty-five percent reported increased caseload
      volume and 48% reported increased caseload complexity during the previous 5
      years. In addition, 75% and 73% denied any recent changes in memory recall or
      name recognition, respectively. Increasing age was associated with decreases in
      clinical caseload and complexity. The majority of respondents across all age
      groups reported active participation in either learning (64%) or contributing
      (13%) to new technology in the field. Among surgeons with no imminent plans for
      retirement, 58% reported that a retirement decision will be based on skill level.
      CONCLUSIONS: Increasing age was associated with decreases in caseload and case
      complexity. But a steady proportion of surgeons, even in the oldest age group,
      are active in new surgical innovations and challenging cases. Most reported no
      changes in perceived cognitive abilities. The majority of surgeons who had made
      no decision to retire reported that their decision will be based on skill level
      rather than age.

PMID- 19854411
TI  - Intrahepatic gallbladder.

PMID- 19854412
TI  - Azygous lobe.

PMID- 19854413
TI  - Plastic surgeons' tradition in transplantation medicine in light of composite
      tissue allotransplantation.

PMID- 19854416
TI  - Emergency traumatologists in trauma care.

PMID- 19854418
TI  - Subspecialization training in PM&R.

PMID- 19854419
TI  - Prospective pilot study of painful lumbar facet joint arthropathy after intra
      articular injection of hylan G-F 20.
AB  - OBJECTIVE: To examine changes in pain, disability, and medication usage over time
      from baseline to up to 12 months after facet joint injection of hylan G-F 20.
      DESIGN: Prospective, uncontrolled, pilot study. SETTING: University spine center.
      PARTICIPANTS: Fifteen patients (12 females), mean age of 57 years (standard
      deviation = 12.5), with a median duration of low back pain of 24 months
      (interquartile range = 11-66). METHODS: Patients who fulfilled inclusion criteria
      underwent diagnostic blocks with local comparative anesthetics at one unilateral
      facet joint (FJ). Those with a true positive response underwent 2 1.0-mL intra
      articular hylan G-F 20 injections, 10 days apart, into the painful FJ. A third
      hylan G-F 20 injection was offered to patients dissatisfied with the results
      obtained with the first 2 injections. MAIN OUTCOME MEASURES: Visual analog scale
      (VAS) (average, standing, walking), Oswestry Disability Index (ODI), SF-36,
      finger to floor distance (FTF), tolerance (standing, sitting, walking), analgesic
      usage, and patient satisfaction collected at baseline, 7-10 days, and at 1-, 3-,
      6-, and 12-months follow-up. RESULTS: Repeated measures mixed-models indicated
      that VAS (average, standing, walking [P all < .005]), ODI (P = .029), SF-36 (P =
      .013), FTF (P = .032), and sitting tolerance (P = .020) all showed significant
      changes from baseline up to 6 months and were not sustained at 12 months; with
      the exception of the baseline to 12-month difference for FTF. There was not
      evidence of changes over time in standing (P = .085) or walking (P = .084)
      tolerance. Satisfaction initially increased from baseline (0%) to 7-10 days (64%)
      but declined over time (36% at 12 months). As compared with baseline (80%),
      analgesic usage decreased nominally over time showing significant decreases at 6
      months (33%, P = .0253) and increased slightly at 12 months (45%). CONCLUSIONS:
      Viscosupplementation for lumbar FJ arthropathy with hylan G-F 20 is associated
      with modest efficacy that predominately lasts up to 6 months. Limitations include
      a small sample size and lack of both a control and blinding. Larger, randomized,
      controlled studies are indicated to better clarify its clinical safety, efficacy,
      and utility.

PMID- 19854421
TI  - Sonographically guided posterior subtalar joint injections: anatomic study and
      validation of 3 approaches.
AB  - OBJECTIVE: To describe and validate 3 different approaches to perform
      sonographically guided posterior subtalar joint (PSTJ) injections. DESIGN:
      Sonographically guided procedures performed on cadaveric specimens. SETTING:
      Procedural skills lab at a tertiary medical facility. METHODS: Three ultrasound
      guided approaches to inject the PSTJ: anterolateral, posteromedial, and
      posterolateral were derived based on anatomic review, published fluoroscopic and
      computed tomography (CT) techniques, and clinical experience. Three separate
      unembalmed cadaveric ankle-foot specimens were injected by a single, experienced
      operator using a 25-gauge, 38-mm stainless steel needle. A different approach was
      used on each specimen. The needles were left in place and each specimen was
      subsequently dissected by co-investigators to confirm accurate needle placement
      and determine the proximity of each needle to local tendons and neurovascular
      structures. MAIN OUTCOME MEASUREMENTS: Direct assessment of needle placement
      within posterior subtalar joint. RESULTS: All 3 approaches provided accurate
      needle placement into the posterior subtalar joint while avoiding nearby
      tendinous and neurovascular structures. CONCLUSIONS: Sonographically guided PSTJ
      injections are technically feasible. All 3 approaches provide accurate needle
      placement while minimizing the risk of needle entry into adjacent soft tissue
      structures not visualized by other modalities such as fluoroscopy or CT.

PMID- 19854422
TI  - Effects of exercise training on calf tissue oxygenation in men with intermittent
      claudication.
AB  - OBJECTIVE: To determine the effects of exercise training on calf tissue
      oxygenation in men with peripheral arterial disease and intermittent calf
      claudication. DESIGN: This pilot study was prospective and longitudinal and used
      a one-group, pretest-posttest design. SETTING: Tertiary care medical center for
      veterans. PARTICIPANTS: Fifteen male veterans (mean age 69 years) with Fontaine
      stage IIa peripheral arterial disease and classic intermittent claudication. MAIN
      OUTCOME MEASUREMENTS: Before and after intervention, participants performed
      graded treadmill exercise tests while medial calf tissue oxygenation (StO(2), %
      oxyhemoglobin saturation) was monitored continuously with near-infrared
      spectroscopy. INTERVENTION: The intervention consisted of a 3-month exercise
      training program involving 3 sessions per week at the clinic (treadmill walking,
      calf ergometry) and 2 sessions per week at home (free walking, standing heel
      raises). RESULTS: After completion of the intervention, participants
      significantly increased their maximal treadmill exercise time from 7.19 to 11.27
      minutes. Mean exercise StO(2) decreased from 29% to 19% saturation, StO(2) x time
      area increased from 421% * min to 730% * min StO(2) nadir, and StO(2) recovery
      time did not change significantly. CONCLUSIONS: After the exercise intervention,
      the improved treadmill walking performance was accompanied by greater calf tissue
      deoxygenation during exercise. Given the continued presence of ischemia, this
      finding may represent increased capillarization and diffusion-based enhancement
      of arteriovenous O(2) extraction.

PMID- 19854420
TI  - Trunk muscle attributes are associated with balance and mobility in older adults:
      a pilot study.
AB  - OBJECTIVE: To determine whether trunk muscle attributes are associated with
      balance and mobility performance among mobility-limited older adults. DESIGN:
      Cross-sectional analysis of data from a randomized clinical trial. SETTING:
      Outpatient rehabilitation research center. PARTICIPANTS: Community-dwelling older
      adults (N = 70; mean age 75.9 years) with mobility limitations as defined by the
      Short Physical Performance Battery (SPPB). METHODS: Independent variables
      included physiologic measures of trunk extension strength, trunk flexion
      strength, trunk extension endurance, trunk extension endurance, and leg press
      strength. All measures were well tolerated by the study subjects without the
      occurrence of any associated injuries or adverse events. The association of each
      physiologic measure with each outcome was examined by the use of separate
      multivariate models to calculate the partial variance (R(2)) of each trunk and
      extremity measure. MAIN OUTCOME MEASUREMENTS: Balance measured by the Berg
      Balance Scale and Unipedal Stance Test and mobility performance as measured by
      the SPPB. RESULTS: Trunk extension endurance (partial R(2) = .14, P = .02), and
      leg press strength (partial R(2) = .14, P = .003) accounted for the greatest
      amount of the variance in SPPB performance. Trunk extension endurance (partial
      R(2) = .17, P = .007), accounted for the greatest amount of the variance in BBS
      performance. Trunk extension strength (R(2) = .09, P = .03), accounted for the
      greatest amount of the variance in UST performance. The variance explained by
      trunk extension endurance equaled or exceeded the variance explained by limb
      strength across all three performance outcomes. CONCLUSIONS: Trunk endurance and
      strength can be safely measured in mobility-limited older adults and are
      associated with both balance and mobility performance. Trunk endurance and trunk
      strength are physiologic attributes worthy of targeting in the rehabilitative
      care of mobility-limited older adults.

PMID- 19854423
TI  - A systematic approach to clinical determinations of causation in symptomatic
      spinal disk injury following motor vehicle crash trauma.
AB  - Clinical determinations of causation in cases of intervertebral disk (IVD) injury
      after a motor vehicle crash (MVC) are often disputed in medicolegal settings. No
      published systematic guidelines exist for making such determinations, which has
      resulted in infringement by nonclinical personnel into injury causation
      evaluations, a traditionally clinical activity. The result is causal
      determinations that are potentially disconnected from clinical observations of
      injury. The purpose of this review was to evaluate the current literature on
      causation, causal determinations after trauma and IVD injury after MVC, and to
      develop a practicable, logical, and literature-based approach to causation
      determinations of symptomatic IVD injury after MVC. The results of the review
      indicate IVD injury can result from any MVC regardless of magnitude, thus meeting
      the first criteria of causation, biologic plausibility. Individual determinations
      of causation depend entirely on the temporal association between the collision
      and the symptom onset (the second criterion) and a lack of a more probable
      explanation for the symptoms (the third). When these causal elements are met,
      clinicians can assert causation on a "more probable than not" or "reasonable
      probability" basis. Because of a lack of an established or reliable relationship
      between collision force and the probability of IVD injury the investigation of
      collision parameters is not a useful adjunct to causal determinations.

PMID- 19854424
TI  - Attending to inclusion: people with disabilities and health-care reform.

PMID- 19854426
TI  - Facet joint procedures: issues of utilization and coverage.

PMID- 19854425
TI  - Debating "interventions" for chronic axial low back pain.

PMID- 19854427
TI  - Autonomic dysreflexia caused by anal fissure.

PMID- 19854428
TI  - The use of nasal trumpet in a traumatic brain injury patient with obstructive
      sleep apnea.

PMID- 19854429
TI  - Standard electrodiagnostic testing may be useful in diagnosing a pure sensory
      lumbar radiculopathy.

PMID- 19854430
TI  - Comments on usage: recording vs pickup electrodes.

PMID- 19854431
TI  - Eye movements during transitive action observation have sequential structure.
AB  - In this paper, we explore how observers of a reach-to-grasp action can identify
      and distinguish between the agent and patient (i.e. target) of the action. We
      investigate the hypothesis that there is a characteristic sequential structure to
      the observer's pattern of saccades, with the agent being fixated first, and then
      the target. We report an experiment which indicates that this sequence of
      saccades, while not ubiquitous, is overwhelmingly more likely than chance. The
      experiment also sheds some light on the mechanisms which allow the observer to
      saccade from the agent of the action to the target.

PMID- 19854432
TI  - Limited economic evaluation to assess the effectiveness of a university-wide
      office ergonomics program.
AB  - The objective of this research was to evaluate the effectiveness and provide a
      limited economic evaluation of an office ergonomics program at a major university
      from 1995 to 2007. The relationship between office-related recordable injuries,
      reported lost time, severity of these injuries, and the Workers' Compensation
      (WC) paid was analyzed and the corresponding incident cost was calculated. Two
      major datasets analyzed were OSHA 200/300 logs (1991-2007) and WC claims paid
      (1999-2007). Since the beginning of the office ergonomics program in 1995 and
      through 2007 (13-year period), the number of office cumulative trauma disorder
      (CTD) cases decreased by 53%. Since the official start (in 1999) of a 50-50 cost
      share agreement for office equipment purchases between the university's Safety
      and Health Department (SHD) and the university departments evaluated, it was
      observed that the incident rate decreased by 63%, Total Days Away/restrict or
      Transfer (DART) rate decreased by 41%, Lost Time Case (LTC) rate decreased by 71%
      and office-related carpal tunnel syndrome decreased by almost 50%. The long-term
      goal of this research is to demonstrate the self-sustainability of an office
      ergonomics program by showing that equipment costs are eventually offset by a
      decrease in WC claims paid and lost time from office-related injuries and
      illnesses. While limited, this research helps in cost-justifying the
      implementation of future office ergonomics programs for large organizations.

PMID- 19854433
TI  - Emotional, cognitive and physiological correlates of abuse-related stress in
      borderline and antisocial personality disorder.
AB  - Childhood abuse is an important precursor of borderline personality disorder
      (BPD) and antisocial personality disorder (ASPD). The current study compared the
      emotional reactivity to abuse-related stress of these patients on a direct and an
      indirect level. Changes in self-reported affect and schema modes,
      psychophysiology and reaction time based cognitive associations were assessed
      following confrontation with an abuse-related film fragment in patients with BPD
      (n=45), ASPD (n=21), Cluster C personality disorder (n=46) and non-patient
      controls (n=36). Results indicated a hyperresponsivity of BPD-patients on self
      reported negative affect and schema modes, on some psychophysiological indices
      and on implicit cognitive associations. The ASPD-group was comparable to the BPD
      group on implicit cognitions but did not show self-reported and physiological
      hyper-reactivity. These findings suggest that BPD and ASPD-patients are alike in
      their implicit cognitive abuse-related stress reactivity, but can be
      differentiated in their self-reported and physiological response patterns.

PMID- 19854434
TI  - Comment on "Decreased Neurokinin-1 (Substance P) Receptor Binding in Patients
      with Panic Disorder: Positron Emission Tomographic Study With [(18)F]SPA-RQ".

PMID- 19854435
TI  - The ACE inhibitors enalapril and captopril modulate cytokine responses in Balb/c
      and C57Bl/6 normal mice and increase CD4(+)CD103(+)CD25(negative) splenic T cell
      numbers.
AB  - Increasing evidence implies beneficial effects of angiotensin-converting enzyme
      (ACE) inhibitors beyond those of their original indications to control
      hypertension. One of the most attractive non-hemodynamic properties of ACE
      inhibitors is their ability to regulate cytokine production. The mechanism(s)
      underlying the role of ACE inhibitors on cytokine synthesis are not well
      understood but they have traditionally been attributed to the inhibition of
      angiotensin (Ang) II formation. In fact, it has been extensively demonstrated
      that ACE inhibitors decrease Ang II-induced production of proinflammatory
      cytokines and chemokines. However, it is not well described if inhibition of
      endogenous Ang II generation by ACE inhibitors modulates systemic cytokine
      production in mice. To verify that, in this work, we investigated the effects of
      treatment with the ACE inhibitors enalapril and captopril on cytokine synthesis
      in C57Bl/6 and Balb/c mice. Our results show that enalapril up regulates IL-10
      produced by splenocytes from Balb/c and C57Bl/6 mice and captopril increased it
      only in Balb/c mice. Furthermore, CD4(+)CD103(+) presented increased IL-10
      production after enalapril treatment. Enalapril as well as captopril short-term
      treatment enhanced IL-2 synthesis in Balb/c mice. Besides, enhanced IL-2 and IL
      10 levels correlates with increased CD4(+)CD103(+)CD25(negative) T cells numbers
      in spleens from enalapril-treated mice.

PMID- 19854437
TI  - A combinatorial feature selection approach to describe the QSAR of dual site
      inhibitors of acetylcholinesterase.
AB  - Regarding the great potential of dual binding site inhibitors of
      acetylcholinesterase as the future potent drugs of Alzheimer's disease, this
      study was devoted to extraction of the most effective structural features of
      these inhibitors from among a large number of quantitative descriptors. To do
      this, we adopted a unique approach in quantitative structure-activity
      relationships. An efficient feature selection method was emphasized in such an
      approach, using the confirmative results of different routine and novel feature
      selection methods. The proposed methods generated quite consistent results
      ensuring the effectiveness of the selected structural features.

PMID- 19854436
TI  - The dark side of incremental learning: a model of cumulative semantic
      interference during lexical access in speech production.
AB  - Naming a picture of a dog primes the subsequent naming of a picture of a dog
      (repetition priming) and interferes with the subsequent naming of a picture of a
      cat (semantic interference). Behavioral studies suggest that these effects derive
      from persistent changes in the way that words are activated and selected for
      production, and some have claimed that the findings are only understandable by
      positing a competitive mechanism for lexical selection. We present a simple model
      of lexical retrieval in speech production that applies error-driven learning to
      its lexical activation network. This model naturally produces repetition priming
      and semantic interference effects. It predicts the major findings from several
      published experiments, demonstrating that these effects may arise from
      incremental learning. Furthermore, analysis of the model suggests that
      competition during lexical selection is not necessary for semantic interference
      if the learning process is itself competitive.

PMID- 19854438
TI  - A practical review of methods for measuring the dynamic characteristics of
      industrial pressure transmitters.
AB  - Three methods exist for testing the response times of pressure transmitters in
      situ: the power interrupt test, the noise analysis technique, and the pink noise
      technique. The noise (or random signal) analysis technique is a passive in situ
      technique that does not interfere with plant operation, uses already existing
      plant sensors and instrumentation, accounts for the effects of process conditions
      on plant equipment performance, and includes any response-time delays caused by
      transmitter sensing lines. The power interrupt test is a simpler and less-time
      consuming test than noise analysis for measuring the response time of force
      balance pressure transmitters. The pink noise test is useful for pressure
      transmitters where process fluctuations do not normally exist or they are
      inadequate for using the noise analysis technique to test response time.

PMID- 19854439
TI  - Prediction of outcome after humeral diaphyseal fracture.
AB  - PURPOSE: The aim of this study is to examine the demographic factors, functional
      outcome and radiological data to predict the outcome of humeral diaphyseal
      fractures. METHODS: We performed a prospective study on a consecutive series of
      110 patients of 16 years or over, who had sustained a humeral diaphyseal
      fracture. There were 42 males and 68 females, with an average age of 59 years
      (range 16-93 years). A total of 72% sustained low-energy injuries, and 89
      patients (81%) were primarily treated non-operatively. Shoulder function was
      assessed using the Neer's and Constant's scores at 8 weeks, 3 months, 6 months
      and 1 year after injury. Muscle strength was determined isokinetically using a
      Biodex System 2 dynamometer. Non-union was defined as a failure to bridge at
      least three cortices and persistence of tenderness or mobility at the fracture
      site 16 weeks after fracture. RESULTS: Sixteen patients (17%) had non-union at 16
      weeks, while 80 had achieved union and a further 14 were lost to follow-up. After
      stepwise multiple linear regression was performed to isolate independent factors
      affecting outcome, only the presence of a proximal diaphyseal fracture was found
      to predict non-union along with a poor Neer's score at 8 and 12 weeks. Poor
      Neer's scores could be predicted at 26 weeks by age (P<0.05), previous stroke
      (P<0.001) and non-union (P<0.001). At 52 weeks both age (P<0.01) and previous
      stroke (P<0.01) were independently predictive of poorer Neer's scores. Malunion
      of any degree had no detectable effect on function. CONCLUSIONS: Our results
      indicate that non-union of humeral diaphyseal fractures can be predicted in the
      presence of a proximal third fracture with a Neer's score of less than 45 by 12
      weeks after fracture. Early surgery improves early function, but this is not a
      lasting effect. Poor shoulder function is predicted by increasing age, proximal
      third fractures and non-union. We recommend that surgery to promote union be
      considered at 12 weeks after fracture in fit patients with fractures of the
      proximal third of the humerus, poor Neer's scores and no radiographic progression
      to union.

PMID- 19854440
TI  - Perceived HIV stigma and life satisfaction among persons living with HIV
      infection in five African countries: a longitudinal study.
AB  - BACKGROUND: Descriptive literature exists on the effects of HIV-related stigma on
      the lives of people living with HIV infection but few empirical studies have
      measured perceived HIV stigma nor explored its potential relationship to quality
      of life (QoL) over time in people living with HIV infection. AIM: A cohort study
      of a purposive convenient sample of 1457 HIV-positive persons was followed for
      one year in a longitudinal design that examined the effects of stigma and the
      life satisfaction dimension of the HIV/AIDS Targeted Quality of Life Instrument
      (HAT-QOL) over time, as well as the influence of other demographic and assessed
      social variables. Data were collected three times about six months apart from
      December 2005 to March 2007. RESULTS: The average age in this sample was 36.8
      years (SD=8.78, n=1454) and 72.7% (n=1056) were female. The initial sample of
      participants was balanced among the five countries: Lesotho, Malawi, South
      Africa, Swaziland, and Tanzania. An attrition analysis demonstrated few
      demographic differences between those who remained in the study 12 months later
      compared with those at baseline. However, those who completed the study and who
      answered the QoL questions had significantly higher life satisfaction scores at
      baseline than those who left the study. There was a general increase in the
      report of life satisfaction QoL in all countries over the one-year period.
      However, as stigma scores increased over time there was a significant decrease in
      life satisfaction with differing rates of change by country. Certain factors had
      a positive influence on life satisfaction QoL: positive HIV media reports, taking
      antiretrovirals, reduced symptom intensity, and disclosure to a friend.
      CONCLUSION: This cohort study is the first to document empirically in a
      longitudinal sample, that perceived HIV stigma has a significantly negative and
      constant impact upon life satisfaction QoL for people with HIV infection. In the
      absence of any intervention to address and reduce stigmatization, individuals
      will continue to report poorer life satisfaction evidenced by reduced living
      enjoyment, loss of control in life, decreased social interactivity, and decreased
      perceived health status.

PMID- 19854441
TI  - Older people's and relatives' experiences in acute care settings: systematic
      review and synthesis of qualitative studies.
AB  - OBJECTIVE: To explore older people's and their relatives' views on and
      experiences of acute health care. DESIGN: Systematic procedures were used for
      study selection and data extraction and analysis. A comparative thematic approach
      to synthesis was taken with a number of features adopted from the literature on
      meta-ethnography. DATA SOURCES: Worldwide grey and published literature written
      in English between January 1999 and June 2008 identified from databases: CINAHL,
      Medline, British Nursing Index, EMBASE Psychiatry, International Bibliography of
      the Social Sciences, PsychINFO, and AgeInfo. REVIEW METHODS: We conducted a
      systematic review and synthesis of qualitative studies describing older patients'
      and/or their relatives' experiences of care in acute hospital settings. 42
      primary studies and 1 systematic review met the inclusion criteria. RESULTS: A
      number of themes emerged. The quality of technical care is often taken for
      granted by older patients, and good or bad experiences are described more in
      terms of relational aspects of care. Older patients in hospital may feel
      worthless, fearful or not in control of what happens, especially if they have
      impaired cognition, or communication difficulties. Three key features of care
      consistently mediated these negative feelings and were linked to more positive
      experiences: "creating communities: connect with me", "maintaining identity: see
      who I am" and "sharing decision-making: include me". CONCLUSION: These findings
      highlight the perspectives of older people and their relatives on the delivery of
      personalized and dignified care in acute settings. They lend support to previous
      calls for relationship-centred approaches to care and provide a useful experience
      based framework for practice for those involved in care for older people.

PMID- 19854442
TI  - Listening to the body and talking to myself - the impact of chronic lower back
      pain: a qualitative study.
AB  - AIMS: The aim was to investigate peoples' experiences of the impact of chronic
      low back pain. BACKGROUND: Chronic low back pain is a complex disorder with wide
      ranging adverse consequences that can impact on people's lifestyles and self
      image. It is also a condition that can sometimes be treated with some scepticism
      by health care providers and other people in the person's life. It has been
      suggested that further research into the subjective experience of chronic blow
      back pain is needed to develop a better understanding of its impact. DESIGN: This
      study is a qualitative analysis of semi-structured interviews with 64
      participants identified as having chronic low back pain who were interviewed
      about the impact of the condition on their lives. The data were analysed using a
      method of inductive thematic analysis. FINDINGS: Four main themes were
      identified: the unpredictability of the pain, the need for vigilance, the
      externalization/objectification of the body and the alteration to sense of self.
      CONCLUSION: Nurses have an important role to play in working with patients
      experiencing chronic low back pain to identify any patterns associated with
      exacerbations of the condition, validating their experiences of chronic low back
      pain and facilitating the accommodation of chronic low back pain into a more
      satisfying sense of self.

PMID- 19854443
TI  - Application of displacement chromatography for the proteome analysis of a human
      plasma protein fraction.
AB  - It was the aim of this study to compare the performance of displacement
      chromatography with gradient elution chromatography both applied as the cation
      exchange separation step for a proteome analysis in a bottom-up approach using
      multidimensional chromatography for the separation of tryptic peptides prior to
      their mass spectrometric analysis. The tryptic digest of the human Cohn fraction
      IV-4 served as a sample. For both chromatography modes commonly used operating
      parameters were chosen thus ensuring optimal separation results of equal sample
      amounts for each mode. All resulting fractions were analyzed with an HPLC-chip-LC
      MS system. The eluate of the HPLC-chip column was ionized by electrospray
      ionization (ESI) and analyzed with an ion-trap mass spectrometer. For
      guaranteeing high confidence concerning the identity of the peptides, the mass
      spectrometric data were processed by different bioinformatic tools applying
      stringent criteria. By the displacement approach the total amount of identified
      proteins (78) was significantly higher than in the gradient mode (58). The
      results showed that displacement chromatography is a well suited alternative in
      comparison to gradient elution separation for analysis of proteomes via the
      bottom-up approach applying multidimensional chromatography, especially in those
      cases when larger quantities of proteins are available.

PMID- 19854444
TI  - Combination of solid phase extraction and in vial solid phase derivatization
      using a strong anion exchange disk for the determination of nerve agent markers.
AB  - Alkylphosphonic acids (APAs) are degradation products and chemical markers of
      organophosphorous (OP) nerve agents (chemical warfare agents). Anion exchange
      disk-based solid phase extraction (SPE) has been combined with in vial solid
      phase derivatization (SPD) and GC-MS analysis for the determination of APAs in
      aqueous samples. The optimization of critical method parameters, such as the SPD
      reaction, was achieved using statistical experimental design and multivariate
      data analysis. The optimized method achieved quantitative recoveries in the range
      from 83% to 101% (n=13, RSD from 4% to 10%). The method was sensitive, with LODs
      in SIM mode of 0.14 ppb, and demonstrated excellent linearity with an average
      R(2)>or=0.99 over the concentration range of 0.07-1.4 ppm in full scan mode and
      from 0.14 ppb to 14 ppb in SIM mode. For forensic applications, aqueous samples
      containing APAs at concentrations exceeding 14 ppb were concentrated and target
      analytes were successfully identified by spectral library and retention index
      matching. Method robustness was evaluated using aqueous samples from the official
      OPCW Proficiency Test (round 19) and all APAs present in the sample were
      conclusively identified. The SPE disk retained the underivatized APAs in a stable
      condition for extended periods of time. No significant losses of APAs from the
      disk were observed over a 36-day period. Overall, the method is well suited to
      the qualitative and quantitative analysis of degradation markers of OP nerve
      agents in aqueous matrices with simplicity, a low risk of cross-contamination and
      trace level sensitivity.

PMID- 19854445
TI  - Matrix-assisted refolding of autoprotease fusion proteins on an ion exchange
      column.
AB  - Refolding of proteins must be performed under very dilute conditions to overcome
      the competing aggregation reaction, which has a high reaction order. Refolding on
      a chromatography column partially prevents formation of the intermediate form
      prone to aggregation. A chromatographic refolding procedure was developed using
      an autoprotease fusion protein with the mutant EDDIE from the N(pro) autoprotease
      of pestivirus. Upon refolding, self-cleavage generates a target peptide with an
      authentic N-terminus. The refolding process was developed using the basic 1.8-kDa
      peptide sSNEVi-C fused to the autoprotease EDDIE or the acidic peptide pep6His,
      applying cation and anion exchange chromatography, respectively. Dissolved
      inclusion bodies were loaded on cation exchange chromatographic resins (Capto S,
      POROS HS, Fractogel EMD SO(3)(-), UNOsphere S, SP Sepharose FF, CM Sepharose FF,
      S Ceramic HyperD F, Toyopearl SP-650, and Toyopearl MegaCap II SP-550EC). A
      conditioning step was introduced in order to reduce the urea concentration prior
      to the refolding step. Refolding was initiated by applying an elution buffer
      containing a high concentration of Tris-HCl plus common refolding additives. The
      actual refolding process occurred concurrently with the elution step and was
      completed in the collected fraction. With Capto S, POROS HS, and Fractogel SO(3)(
      ), refolding could be performed at column loadings of 50mg fusion protein/ml gel,
      resulting in a final eluate concentration of around 10-15 mg/ml, with refolding
      and cleavage step yields of around 75%. The overall yield of recovered peptide
      reached 50%. Similar yields were obtained using the anion exchange system and the
      pep6His fusion peptide. This chromatographic refolding process allows processing
      of fusion peptides at a concentration range 10- to 100-fold higher than that
      observed for common refolding systems.

PMID- 19854446
TI  - In situ synthesis of Ag nanoparticles in aminocalix[4]arene multilayers.
AB  - The layer-by-layer (LbL) assembled thin films containing tetraamino
      thiacalix[4]arenes (1) and tetraamino-calix[4]arenes (2) were used as nanoreactor
      to synthesize in situ Ag nanoparticles (Ag NPs). UV-vis spectra and AFM images
      demonstrate that Ag NPs are included in the (1/Ag NPs)(n) and (2/Ag NPs)(n)
      multilayer films. The silver ions are absorbed through cation-pi interaction and
      calix[4]arene-metal ion coordination interaction and are reduced into Ag NPs by
      calix[4]arenes. TEM images indicated that Ag NPs within aminocalix[4]arene
      multilayers were highly dispersed and uniform. Moreover, the mean size of Ag NPs
      is smaller than 10 nm.

PMID- 19854447
TI  - Reductive dissolution of ferrihydrite by ascorbic acid and the inhibiting effect
      of phospholipid.
AB  - The interaction of ascorbic acid with ferrihydrite nanoparticles with and without
      adsorbed phospholipid has been investigated with atomic force microscopy (AFM),
      attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR),
      density functional theory (DFT) cluster calculations, and batch geochemical
      methods. Both batch geochemical rate measurements and in situ AFM showed that
      ferrihydrite particles dissolved in the presence of ascorbic acid over a period
      of hours. The area-normalized dissolution rate derived from AFM measurements of
      isolated ferrihydrite particles was relatively constant over the period of
      dissolution and was faster than the dissolution rate derived from batch reaction
      methods. Results from ATR-FTIR interpreted in view of theoretical calculations
      suggested that exposure of ferrihydrite to ascorbic acid led to an adsorbed
      monodentate ascorbate surface complex. Ferrihydrite dissolution was suppressed if
      particles were exposed to an organic lipid prior to or during exposure to
      ascorbic acid. AFM analysis of the lipid layer showed that its thickness was
      close to 7 nm, the expected value for lipid assembled into a bilayer structure.

PMID- 19854448
TI  - Modulating the catalytic activity of Au/micelles by tunable hydrophilic channels.
AB  - Polymeric micelles with a polystyrene core, poly(acrylic acid)/poly(4-vinyl
      pyridine) (PAA/P4VP) complex shell and poly(ethylene glycol) & poly(N
      isopropylacrylamide) (PEG & PNIPAM) mixed corona were synthesized and used as the
      supporter for the gold nanoparticles (GNs). It was concluded from the result of
      (1)H NMR characterization that hydrophilic channels formed around PEG chains when
      PNIPAM collapsed above its lower critical solution temperature. The density of
      the channels in the corona can be tuned by changing the weight ratios of PEG
      chains to PNIPAM chains. The GNs were set in the PAA/P4VP complex layer and the
      catalytic activity of the GNs can be modulated by the channels. The catalytic
      activity increased with increasing the density of the channels in the corona.
      Meanwhile, the whole Au/micelle nanoparticles were stabilized by the extended PEG
      chains.

PMID- 19854449
TI  - The contribution of processing impairments to SLI: insights from attention
      deficit/hyperactivity disorder.
AB  - Slowed speed of processing and impaired rapid temporal processing (RTP) have been
      proposed to underlie specific language impairment (SLI), but it is not clear that
      these dysfunctions are unique to SLI. We considered the contribution of attention
      deficit/hyperactivity disorder (ADHD), which frequently co-occurs with language
      impairments, to performances on processing tasks. School-aged children who had
      SLI without concurrent ADHD (n=14), ADHD without concurrent SLI (n=14), and
      typical development (TD, n=28) performed two nonverbal speeded tasks and one
      auditory RTP task. RTP impairments were found in many children with SLI and ADHD,
      and some children with TD. Children with ADHD demonstrated slower processing
      speed than children with SLI or TD. Overall, findings questioned the uniqueness
      of these processing dysfunctions to language impairments and the validity of the
      behavioural paradigms traditionally used to estimate processing dysfunctions.
      Accounts of SLI should be further scrutinized by considering the influence of
      other disorders. LEARNING OUTCOMES: Readers will (1) become familiar with areas
      of overlap between SLI and ADHD, (2) understand some of the confounds associated
      with behavioural measures of processing speed in children, and (3) recognize the
      value in testing models of language disorders by including participants with
      other types of disorders.

PMID- 19854450
TI  - Ethanol preconditioning reduces hepatic I/R injury by inhibiting the complement
      system activation.
AB  - BACKGROUND: Ethanol preconditioning (EtOH-PC) refers to a phenomenon in which
      cerebral, intestinal, and myocardial tissues are protected from the deleterious
      effects of ischemia/reperfusion (I/R) by prior ingestion of ethanol at low to
      moderate levels. Whether EtOH-PC can offer protective effects against hepatic I/R
      injury and whether these effects are associated with inhibition of complement
      activation were investigated. METHODS: Male SD rats were divided into four
      groups, i.e., sham operation, ethanol control, IR, and ethanol-pretreatment I/R
      (EIR) groups. EtOH-PC was induced by gavaging rats with 40% ethanol at a dose of
      5 g/kg body weight 24 h prior to experiment. Animal survival rate was compared.
      Liver function, hepatic MDA level, plasma complement C3 level, and serum
      hemolytic activity were determined. Histologic changes and complement C3
      deposition in liver section were examined. Expression of liver complement 3 mRNA
      was analyzed by quantitative real-time -PCR. RESULTS: The 14-d survival rates
      were remarkably higher in the EIR groups than in the corresponding IR groups when
      hepatic ischemia time was 110, 120, and 130 min. Serum ALT, AST, IL-1beta, and
      liver tissue MDA were significantly lower, and histopathologic changes
      significantly milder in the EIR group than in the IR group (P <0.05). Compared
      with the IR group, both the reduction in CH50 and plasma C3 were significantly
      suppressed, and the staining of C3 in liver tissue significantly reduced in the
      EIR group. There were no significant differences of hepatic C3 mRNA among four
      groups. CONCLUSIONS: Ethanol preconditioning reduces hepatic I/R injury, and the
      effect is associated with inhibition of complement activation.

PMID- 19854451
TI  - Elevated monocytes in patients with critical limb ischemia diminish after bypass
      surgery.
AB  - BACKGROUND: Mononuclear cells (MNC) increase neovascularization and ulcer healing
      after injection into an ischemic extremity. Circulating MNC are composed of
      lymphocytes (85%), monocytes (15%), and endothelial progenitor cells (EPC;
      0.03%). We hypothesized that ischemic limbs secrete paracrine signals to recruit
      bone marrow-derived monocytes and EPC into the circulation, such that patients
      with critical limb ischemia (CLI) have increased circulating monocytes compared
      with control patients. We also hypothesized that circulating monocytes and EPC
      recruitment decrease after resolution of ischemia with successful
      revascularization. METHODS: We reviewed the records of all patients at the VA
      Connecticut Healthcare System undergoing primary, functionally successful, lower
      extremity peripheral bypass surgery between 2002 and 2007, but only including
      patients with both preoperative and postoperative (>4 mo) complete blood counts
      with differentials. RESULTS: Patients with CLI (n = 24) had elevated preoperative
      monocyte counts compared with control patients (n = 8) (0.753 +/- 0.04 versus
      0.516 +/- 0.05; P = 0.0046), whereas the preoperative lymphocyte counts were not
      significantly different. After revascularization, ischemic patients had decreased
      monocyte counts compared with control patients (-20% versus + 55%; P = 0.0003),
      although lymphocyte counts were unchanged in both groups. Diabetic patients also
      had reduced postoperative monocyte counts (-32% versus + 13%; P = 0.035).
      Multivariable logistic regression demonstrated that the only factor that
      independently predicted reduced postoperative monocyte count was preoperative CLI
      (P = 0.038). CONCLUSIONS: Patients with CLI have increased numbers of circulating
      monocytes, and the monocyte number decreases with resolution of ischemia after
      successful revascularization. Circulating monocytes may be a clinically useful
      perioperative marker in patients with CLI undergoing vascular surgery.

PMID- 19854452
TI  - Hypoperfusion of the motor cortex associated with parkinsonism in dementia with
      Lewy bodies.
AB  - OBJECTIVE: This study aimed to investigate the impact of parkinsonism on regional
      cerebral blood flow (rCBF) in dementia with Lewy bodies (DLB). METHOD: Forty-four
      probable DLB patients, comprising 13 patients without parkinsonism and 31
      patients with parkinsonism, and 16 normal controls were selected for this study.
      We evaluated the rCBF in each group by means of N-isopropyl-p-[(123)I]
      iodoamphetamine (IMP) and single photon emission computed tomography (SPECT). The
      rCBF in the different groups was compared using voxel-by-voxel Statistical
      Parametrical Mapping (SPM). RESULT: Patients with DLB showed low rCBF in the
      frontal, temporal, and occipital cortex with relative sparing of the paracentral
      region. DLB patients with parkinsonism (DLB-P) had lower rCBF in the primary
      motor cortex (M1) and left supplementary motor area (SMA) than DLB patients
      without parkinsonism (DLB-nonP). DLB-nonP patients showed decreased rCBF in the
      left temporo-occipital region. CONCLUSION: This study suggests that two distinct
      clinical entities are involved in DLB. In addition, CBF changes in the M1 and SMA
      are seen in the early stages of Parkinson's disease. This result would help in
      diagnosing DLB in the context of Lewy body (LB) disease.

PMID- 19854454
TI  - Long-term divergent tidal flat benthic community recovery following hypoxia
      induced mortality.
AB  - Macrobenthos recovery after hypoxia-induced mass mortality was assessed in an
      estuarine tidal mudflat during 3 years. During the first 2 years, a Pearson
      Rosenberg type of community recovery took place along with the improving bottom
      water oxygen conditions. After 3 months, spionid polychaetes became superabundant
      (i.e. opportunistic peak), followed rapidly by a steep decline (i.e. ecotone
      point). Subsequently, a moderate increase in species richness and a steep
      increase in biomass, related to the growth of long-lived species occurred (i.e.
      transition region). Afterwards, however, the recovering community diverged again
      from the ambient, undisturbed, sediments due to enhanced recruitment success of
      long-lived species presumably resulting from the lowered interference from
      bioturbation during early recovery stages in the disturbed plots. Hence, despite
      early community recovery may be more or less deterministic, lagged divergent
      community reassembling may occur at the longer-term, thereby contributing to
      benthos patchiness in areas which are frequently subjected to disturbances.

PMID- 19854453
TI  - Current nonylphenol pollution and the past 30 years record in an artificial Lake
      Shihwa, Korea.

PMID- 19854455
TI  - An exploratory study of the perceived impact of raising the age of cigarette
      purchase on young smokers in Scotland.
AB  - OBJECTIVES: To explore the perceived impact among a group of Scottish 16- and 17
      year-old school leavers of the recent increase in age of sale of cigarettes (1
      October 2007) from 16 to 18 years on their ability to purchase and access
      cigarettes. STUDY DESIGN: Qualitative interviews with friendship pairs. METHODS:
      Twelve paired qualitative interviews conducted in June 2008. Participants were 16
      and 17-year-old early school leavers undertaking a work skills programme in
      Lothian who smoked at least one cigarette per week. Data were analysed
      thematically. RESULTS: The increase in the age of sale affected participants'
      perceived ability to purchase cigarettes to differing extents. Three groups were
      identified: those who were unable to purchase cigarettes either before or after
      the change in the law, those who could purchase cigarettes before the change in
      the law but who found it very difficult to do so afterwards, and those who were
      relatively unaffected as they could purchase cigarettes both before and after the
      age was raised to 18 years, mostly from small corner shops. Smoking was embedded
      in participants' social lives and networks. Thus, there was only a limited impact
      upon their reported ability to access cigarettes due to the availability of
      alternative social sources of cigarettes from family, friends and others.
      CONCLUSIONS: This exploratory study raises questions about the nature and extent
      of the impact of raising the age of sale on young smokers' ability to purchase
      and access cigarettes. The importance of alternative social sources of cigarettes
      highlights the need for further research to investigate whether the change in
      legislation had less of an impact on more disadvantaged adolescent smokers, as
      they are likely to have greater access to alternative sources from their family,
      friends and community.

PMID- 19854456
TI  - An evaluation of the effectiveness of 'Active for Life': an exercise referral
      scheme in West Suffolk.

PMID- 19854457
TI  - Association between levels of physical activity and poor self-rated health in
      Korean adults: The Third Korea National Health and Nutrition Examination Survey
      (KNHANES), 2005.
AB  - OBJECTIVE: To investigate the association between level of physical activity and
      poor self-rated health in Korean adults. STUDY DESIGN: A cross-sectional study
      was conducted on 7,800 adults aged > or =19 years who completed the Health
      Interview and the Health Behavior Surveys, issued during the Third National
      Health and Nutrition Examination Survey (2005). METHODS: The association between
      self-rated health and physical activity was tested using Chi-squared test.
      Multiple logistic regression analysis was used to calculate the odds ratios of
      poor self-rated health for different levels of physical activity after adjusting
      for physical and chronic medical conditions. RESULTS: The prevalence of poor self
      rated health was significantly lower as the level of physical activity increased,
      and odds ratios for poor self-rated health were significantly lower for higher
      levels of physical activity after adjusting for age, marital status, educational
      status, smoking, alcohol consumption, and the number of physical impairments and
      chronic medical conditions. The association was similar in different age groups
      and among healthy respondents and respondents with physical impairments or
      chronic medical conditions. CONCLUSIONS: Physical activity was positively
      associated with self-rated health in Koreans. The independent association between
      a lower level of physical activity and poor self-rated health supports public
      health programmes that encourage regular physical activity.

PMID- 19854458
TI  - Ultrasound propagation in wet and airless non-consolidated granular materials.
AB  - This paper deals with an experimental description of the acoustic behaviour of
      non-consolidated granular materials submitted to static force. The aim of this
      work is to investigate the effect of a small amount of an interstitial fluid on
      the acoustic propagation. Measurements of the velocity and of the transmission of
      the coherent wave are performed for different values of the applied force. It is
      shown that the behaviour of the speed of the ultrasonic coherent wave according
      to pressure have a slope close to the one of the Hertz-Mindlin's model in the
      case of a dry medium. When a small amount of a low viscosity fluid is added in a
      mono-disperse granular medium, the speed of the ultrasonic wave increases
      according to the power 1/6 to the force applied following the Hertz-Mindlin law
      (v approximately P(1/6)). Moreover, measurements of the velocity and of the
      transmission of the ultrasonic wave are strongly dependent on the nature of the
      interstitial fluid. In order to quantify its effect on the propagation,
      measurements are performed using various fluids having different characteristics.
      In a first step, silicon oils of different viscosities (from 50 x 10(-3) to 10 Pa
      s) are used, showing that with increasing viscosity, the wave velocity no longer
      varies according to the power law 1/6. The transmission coefficient also
      increases with the viscosity, showing a better propagation of the wave through
      the medium. Then, measurements are done in the vacuum allowing a comparison with
      ultrasonic propagation in presence of an interstitial fluid. This experiment
      shows a strong increase of the transmission coefficient while velocity remains
      the same as in the dry case. The study of scattered waves in vacuum shows also a
      significant increase in amplitude and duration of these typical waves. Then,
      different saturating inert gases are added to the medium showing that the
      propagation of the scattered wave is not influenced by their different
      characteristics.

PMID- 19854459
TI  - Nipah virus entry can occur by macropinocytosis.
AB  - Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged
      recently in Asia with high mortality in man. NiV is a member, with Hendra virus
      (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV
      entry, like that of other paramyxoviruses, is believed to occur via pH
      independent fusion with the host cell's plasma membrane we present evidence that
      entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor
      kinase activity and we find that ephrinB2's cytoplasmic domain is required for
      entry but is dispensable for post-entry viral spread. The mutation of a single
      tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry.
      Moreover, our results show that NiV entry is inhibited by constructions and drugs
      specific for the endocytic pathway of macropinocytosis. Our findings could
      potentially permit the rapid development of novel low-cost antiviral treatments
      not only for NiV but also HeV.

PMID- 19854460
TI  - Infection of bovine dendritic cells by rinderpest or measles viruses induces
      different changes in host transcription.
AB  - The morbilliviruses are a closely related genus which are very similar in their
      sequences and share a common receptor, but nevertheless show significant
      restriction in the host species in which they cause disease. One contribution to
      this restriction might be the nature of the hosts' responses to infection. We
      have used microarrays to study the changes in the transcriptome of bovine
      dendritic cells after infection with wild-type (pathogenic) and vaccine
      (apathogenic) strains of rinderpest virus (RPV), a bovine pathogen, and a wild
      type isolate of measles virus (MV), a morbillivirus that causes disease only in
      humans and some other primates. We found that, as previously observed in human
      cells, MV induces a rapid interferon response, while that induced by RPV was
      delayed and much reduced in magnitude. Pathogenic and apathogenic RPV also showed
      significant differences, with the latter inducing a slightly higher interferon
      response as well as significant effects on transcription of genes involved in
      cell cycle regulation.

PMID- 19854461
TI  - Transgene expression by oncolytic adenoviruses is modulated by E1B19K deletion in
      a cell type-dependent manner.
AB  - Major strategies to increase oncolytic adenovirus efficacy, as required for
      clinical applications, are enhancing oncolysis by acceleration of virus
      release/spread and "arming" by insertion of therapeutic genes. We investigated
      whether these strategies can be effectively combined as it has been speculated
      that the arming approach rather benefits from delayed cell lysis and extended
      time for protein synthesis. We report that deleting adenoviral E1B19K results in
      an apoptosis-dependent early viral release and thus enhanced oncolysis in several
      tumor cells, but inhibits virus replication in others. In the former case,
      apoptosis induction and early cell lysis did not interfere with late transgene
      expression. Thus, transgene expression was dramatically increased over time due
      to better virus spread. In A549 cells, transgene expression by the E1B19K(-)
      virus at 5 days post-infection was higher than for the E1B19K(+) virus at 10
      days. These properties may be of critical importance in patients, where time for
      virus spread is limited.

PMID- 19854462
TI  - Environmental fate and toxicity of ionic liquids: a review.
AB  - Ionic liquids (ILs) are organic salts with low melting point that are being
      considered as green replacements for industrial volatile organic compounds. The
      reputation of these solvents as "environmental friendly" chemicals is based
      primarily on their negligible vapor pressure. Nonetheless, the solubility of ILs
      in water and a number of literature documenting toxicity of ILs to aquatic
      organisms highlight a real cause for concern. The knowledge of ILs behavior in
      the terrestrial environment, which includes microbial degradation, sorption and
      desorption, is equally important since both soil and aquatic milieu are possible
      recipients of IL contamination. This article reviews the achievements and current
      status of environmental risk assessment of ILs, and hopefully provides insights
      into this research frontier.

PMID- 19854463
TI  - Loadings, trends, comparisons, and fate of achiral and chiral pharmaceuticals in
      wastewaters from urban tertiary and rural aerated lagoon treatments.
AB  - A comparison of time-weighted average pharmaceutical concentrations, loadings and
      enantiomer fractions (EFs) was made among treated wastewater from one rural
      aerated lagoon and from two urban tertiary wastewater treatment plants (WWTPs) in
      Alberta, Canada. Passive samplers were deployed directly in treated effluent for
      nearly continuous monitoring of temporal trends between July 2007 and April 2008.
      In aerated lagoon effluent, concentrations of some drugs changed over time, with
      some higher concentrations in winter likely due to reduced attenuation from lower
      temperatures (e.g., less microbially mediated biotransformation) and reduced
      photolysis from ice cover over lagoons; however, concentrations of some drugs
      (e.g. antibiotics) may also be influenced by changing use patterns over the year.
      Winter loadings to receiving waters for the sum of all drugs were 700 and 400
      g/day from the two urban plants, compared with 4 g/day from the rural plant. Per
      capita loadings were similar amongst all plants. This result indicates that
      measured loadings, weighted by population served by WWTPs, are a good predictor
      of other effluent concentrations, even among different treatment types. Temporal
      changes in chiral drug EFs were observed in the effluent of aerated lagoons, and
      some differences in EF were found among WWTPs. This result suggests that there
      may be some variation of microbial biotransformation of drugs in WWTPs among
      plants and treatment types, and that the latter may be a good predictor of EF for
      some, but not all drugs.

PMID- 19854464
TI  - Enhanced transformation of triclosan by laccase in the presence of redox
      mediators.
AB  - Triclosan (TCS), an antimicrobial agent, is an emerging and persistent
      environmental pollutant that is often found as a contaminant in surface waters
      and sediments; hence, knowledge of its degradability is important. In this study
      we investigated laccase-mediated TCS transformation and detoxification, using
      laccase (from the fungus Ganoderma lucidum) in the presence and absence of redox
      mediators. Transformation products were identified using HPLC, ESI-MS and GC-MS,
      and transformation mechanisms were proposed. In the absence of redox mediator,
      56.5% TCS removal was observed within 24h, concomitant with formation of new
      products with molecular weights greater than that of TCS. These products were
      dimers and trimers of TCS, as confirmed by ESI-MS analysis. Among the various
      mediators tested, 1-hydroxybenzotriazole (HBT) and syringaldehyde (SYD)
      significantly enhanced TCS transformation ( approximately 90%). The presence of
      these mediators resulted in products with lower molecular weights than TCS,
      including 2,4-dichlorophenol (2,4-DCP; confirmed by GC-MS) and dechlorinated
      forms of 2,4-DCP. When SYD was used as the mediator, dechlorination resulted in 2
      chlorohydroquinone (2-CHQ). Bacterial growth inhibition studies revealed that
      laccase-mediated transformation of TCS effectively decreased its toxicity, with
      ultimate conversion to less toxic or nontoxic products. Our results confirmed the
      involvement of two mechanisms of laccase-catalyzed TCS removal: (i)
      oligomerization in the absence of redox mediators, and (ii) ether bond cleavage
      followed by dechlorination in the presence of redox mediators. These results
      suggest that laccase in combination with natural redox mediator systems may be a
      useful strategy for the detoxification and elimination of TCS from aqueous
      systems.

PMID- 19854465
TI  - Monitoring the biological activity of micropollutants during advanced wastewater
      treatment with ozonation and activated carbon filtration.
AB  - A bioanalytical test battery was used to monitor the removal efficiency of
      organic micropollutants during advanced wastewater treatment in the South
      Caboolture Water Reclamation Plant, Queensland, Australia. This plant treats
      effluent from a conventional sewage treatment plant for industrial water reuse.
      The aqueous samples were enriched using solid-phase extraction to separate some
      organic micropollutants of interest from metals, nutrients and matrix components.
      The bioassays were chosen to provide information on groups of chemicals with a
      common mode of toxic action. Therefore they can be considered as sum indicators
      to detect certain relevant groups of chemicals, not as the most ecologically or
      human health relevant endpoints. The baseline toxicity was quantified with the
      bioluminescence inhibition test using the marine bacterium Vibrio fischeri. The
      specific modes of toxic action that were targeted with five additional bioassays
      included aspects of estrogenicity, dioxin-like activity, genotoxicity,
      neurotoxicity, and phytotoxicity. While the accompanying publication discusses
      the treatment steps in more detail by drawing from the results of chemical
      analysis as well as the bioanalytical results, here we focus on the applicability
      and limitations of using bioassays for the purpose of determining the treatment
      efficacy of advanced water treatment and for water quality assessment in general.
      Results are reported in toxic equivalent concentrations (TEQ), that is, the
      concentration of a reference compound required to elicit the same response as the
      unknown and unidentified mixture of micropollutants actually present. TEQ proved
      to be useful and easily communicable despite some limitations and uncertainties
      in their derivation based on the mixture toxicity theory. The results obtained
      were reproducible, robust and sensitive. The TEQ in the influent ranged in the
      same order of magnitude as typically seen in effluents of conventional sewage
      treatment plants. In the initial steps of the treatment chain, no significant
      degradation of micropollutants was observed, and the high levels of dissolved
      organic carbon probably affected the outcome of the bioassays. The steps of
      coagulation/flocculation/dissolved air flotation/sand filtration and ozonation
      decreased the effect-based micropollutant burden significantly.

PMID- 19854466
TI  - Evaluation of power ultrasound for disinfection of both Legionella pneumophila
      and its environmental host Acanthamoeba castellanii.
AB  - The objectives of this study were to (1) examine the effect of power ultrasound
      on the viability of both Legionella pneumophila and Acanthamoeba castellanii
      trophozoites and cysts, (2) investigate if intracellular Legionella replication
      in trophozoites positively affects bacterial resistance to ultrasound and (3)
      study if Legionella renders viable but non-culturable (VBNC) due to ultrasound
      treatments. Using laboratory scale experiments, microorganisms were exposed for
      various time periods to power ultrasound at a frequency of 36 kHz and an
      ultrasound power setting of 50 and 100%. Due to a fast destruction, trophozoite
      hosts were not able to protect intracellular Legionella from eradication by
      ultrasound, in contrast to cysts. No significant effects of ultrasound on cyst
      viability could be detected and power settings of 100% for 30 min only made
      intracellular Legionella concentrations decrease with 1.3 log units. Due to
      intracellular replication of Legionella in trophozoites, ultrasound no longer
      affected bacterial viability. Concerning the VBNC state, ultrasound treatments
      using a power setting of 50% partly induced Legionella (+/-7%) to transform into
      VBNC bacteria, in contrast to power settings of 100%. Promising results obtained
      in this study indicate the possible application of power ultrasound in the
      control of both Legionella and Acanthamoeba concentrations in anthropogenic water
      systems.

PMID- 19854467
TI  - Coupled factors influencing the transport and retention of Cryptosporidium parvum
      oocysts in saturated porous media.
AB  - The coupled role of solution ionic strength (IS), hydrodynamic force, and pore
      structure on the transport and retention of viable Cryptosporidium parvum oocyst
      was investigated via batch, packed-bed column, and micromodel systems. The
      experiments were conducted over a wide range of IS (0.1-100 mM), at two Darcy
      velocities (0.2 and 0.5 cm/min), and in two sands (median diameters of 275 and
      710 microm). Overall, the results suggested that oocyst retention was a complex
      process that was very sensitive to the solution IS, the Darcy velocity, and the
      grain size. Increasing IS led to enhanced retention of oocysts in the column,
      which is qualitatively consistent with predictions of Derjaguin-Landau-Verwey
      Overbeek theory. Conversely, increasing velocity and grain size resulted in less
      retention of oocysts in the column due to the difference in the fluid drag force
      and the rates of mass transfer from the liquid to the solid phase and from high
      to low velocity regions. Oocyst retention was controlled by a combined role of
      low velocity regions, weak attractive interactions, and/or steric repulsion. The
      contribution of each mechanism highly depended on the solution IS. In particular,
      micromodel observations indicated that enhanced oocyst retention occurred in low
      velocity regions near grain-grain contacts under highly unfavorable conditions
      (IS=0.1 mM). Oocyst retention was also found to be influenced by weak attractive
      interactions (induced by the secondary energy minimum, surface roughness, and/or
      nanoscale chemical heterogeneity) when the IS=1 mM. Reversible retention of
      oocysts to the sand in batch and column studies under favorable attachment
      conditions (IS=100 mM) was attributed to steric repulsion between the oocysts and
      the sand surface due to the presence of oocyst surface macromolecules. Comparison
      of experimental observations and theoretical predictions from classic filtration
      theory further supported the presence of this weak interaction due to steric
      repulsion.

PMID- 19854468
TI  - Mullerian mucinous borderline tumors.

PMID- 19854469
TI  - Water management--a tool for methane mitigation from irrigated paddy fields.
AB  - Water drainage is considered to be one of the important practices that reduce the
      CH(4) efflux from paddy fields. In this study, four different drainage systems
      (continuous flooding, tillering stage drainage, mid-season drainage and multiple
      drainage) were compared to find out the best one, for attenuation of CH(4)
      emission from rice fields. Except for continuous flooding, from all the other
      three drainage systems, irrigation water from the paddy fields was drained out at
      the different stages of the crop cycle. Highest efflux of the methane was
      recorded from continuously flooded plots (346.6 mg/m(2)/day), followed by 9% less
      CH(4) efflux from tillering stage drainage (315.1mg/m(2)/day), 36.7% less efflux
      from mid-season drainage (219.3mg/m(2)/day) and the least 41% CH(4) efflux from
      multiple drainage plots (204.7 mg/m(2)/day). Among all the four different
      drainage systems applied, mid-season drainage and multiple drainage were found to
      be highly effective in mitigating methane efflux. Redox potential of the soil of
      the drainage system was found to be inversely proportional to the methane efflux
      from all the treatments.

PMID- 19854470
TI  - Nonmethane hydrocarbon measurements at a suburban site in Changsha City, China.
AB  - The concentration, composition, and variability of nonmethane hydrocarbons
      (NMHCs) and carbon monoxide (CO) were characterized in a suburban region of south
      central China. Weekly samples were collected in 2007 in the Changsha suburban
      area and analyzed with a three-stage preconcentration method coupled with GC-MS.
      A time series of NMHC measurements showed seasonal variation, with a higher level
      occurring in winter and a lower level in summer. Toluene was the most abundant
      species with an average concentration of 2.51+/-1.87 ppbv, followed by benzene
      (2.04+/-1.30 pptv). According to the level of identified NMHCs, vehicular exhaust
      appears to be the main source of NMHCs in Changsha. Among alkanes, the highest
      level is propane with a concentration of 1.31+/-0.71 ppbv, it indicated an
      extensive use and leakage of liquefied petroleum gas (LPG) in Changsha. The
      concentrations of NMHCs were influenced by the wind direction; a high level of
      NMHCs was carried by winds from southern China. Significant biogenic isoprene
      emissions were observed, with good correlation between isoprene level and
      temperature. Finally, when the typical individual NMHC species and CO in the
      morning and afternoon were compared, the shorter lifetime of NMHC species
      relative to CO could explain the poorer correlation observed in the afternoon.

PMID- 19854471
TI  - Increased microparticle tissue factor activity in cancer patients with Venous
      Thromboembolism.
AB  - Cancer patients exhibit a high rate of thromboembolism (VTE). In this study, we
      analyzed levels of microparticle (MP) tissue factor (TF) activity in cancer
      patients with or without VTE. Blood was collected from cancer patients within 24
      h of objectively diagnosed VTE (n=53) and from cancer patients without VTE
      (n=13). MPs were isolated from platelet poor plasma by centrifugation at 20,000g
      for 15 min. MP TF activity was measured using a two-stage chromogenic assay.
      Cancer patients with VTE had a significantly higher mean MP TF activity compared
      with cancer patients without VTE (1.7+/-3.8 pg/mL vs 0.6+/-0.4 pg/mL, p<0.05).
      Further prospective studies are required to determine if levels of MP TF activity
      may be a useful biomarker to identify patients at increased risk for VTE.

PMID- 19854472
TI  - Treatment of the critically ill patient with protein C: is it worth the cost?
AB  - INTRODUCTION: We have shown that low protein C levels predict poor survival up to
      five years in a general intensive care unit patient material and hypothesize that
      treatment with protein C is beneficial. The objectives were to calculate costs of
      protein C treatment, at best-case scenario, per statistical life saved. MATERIALS
      AND METHODS: Ninety-two patients with deranged global haemostatic tests admitted
      to the mixed surgical medical intensive care unit, Malmo University Hospital. We
      hypothesized that increasing protein C levels in patients with low levels would
      enhance survival to the same rate as a cohort with higher protein C. Number of
      statistical lives saved were estimated using survival analysis. Costs per life
      saved at 30days were calculated. RESULTS: Total costs per life saved in 2007
      prices (upper limit of 95% CI) were calculated at euro 50,200 (recombinant
      activated protein C, drotrecogin alfa (activated), Xigris) and euro 46,000
      (zymogen protein C, Ceprotin), which may be compared to the value of a
      statistical life (euro 937,000). CONCLUSIONS: Our theoretical model of converting
      a low protein C group to a higher protein C group by treating with activated
      protein C or the protein zymogen showed no major difference between the
      treatments in terms of costs, and that costs are lower than the value of a
      statistical life. Although our study has several caveats the results support the
      PROWESS study, in that patients with a very severe disease, having low protein C
      levels, may benefit from protein C treatment in a cost effective way.

PMID- 19854473
TI  - Expression and localization of hypoxia proteins in prostate cancer: prognostic
      implications after radical prostatectomy.
AB  - OBJECTIVES: To uncover novel biomarkers that will help predict which patients are
      at risk and may guide future treatment decisions. A significant proportion of
      prostate cancer patients treated with radical prostatectomy will experience a
      recurrence of the disease. Given the substantial role of hypoxia in prostate
      cancer development and treatment, this investigation focuses on the Hypoxia
      Inducible Factor (HIF-1alpha) pathway. METHODS: A tissue microarray was
      constructed of prostate cancer tissue collected from 71 patients undergoing
      radical prostatectomy. The expression of proteins involved in the HIF-1alpha
      pathway was investigated by an immunohistochemical approach and correlated to
      clinical features including the time to biochemical recurrence. RESULTS:
      Expression of GLUT1 correlated significantly (P <.05) with a shorter time to
      biochemical recurrence after radical prostatectomy and was independent from the
      Gleason grade and stage of cancer. Furthermore, our studies revealed for the
      first time that accumulation of prolyl-4-hydroxylases 1 especially in the
      nucleus, is a significant indicator for a worse prognosis (P <.001). CONCLUSIONS:
      This study confirms the upregulation of proteins involved in the HIF-1alpha
      hypoxia pathway in prostate cancer cells, indicative of a hypoxic tumor state.
      Importantly, we report the identification of 2 novel markers, GLUT1 and prolyl-4
      hydroxylases 1, with prognostic significance for patients undergoing radical
      prostatectomy.

PMID- 19854474
TI  - Recoverability of renal function after relief of chronic partial unilateral
      ureteral obstruction: study of the effect of angiotensin receptor blocker
      (losartan).
AB  - OBJECTIVES: To evaluate the effect of angiotensin receptor blocker (losartan) on
      renal function during and after relief of partial unilateral ureteral obstruction
      (PUO). METHODS: A total of 32 male mongrel dogs were classified into 3 groups:
      sham (8), control (12; left PUO + no medications), and study (12; left PUO +
      losartan). Dogs of the study and control groups were subjected to 4 weeks of PUO.
      After that, they were reopened and subjected to Lich-Grigoir ureterovesical
      reimplantation and then were killed by the end of 32 weeks after relief of
      obstruction after being evaluated at basal condition; fourth week of obstruction;
      and at 4, 8, and 32 weeks after relief of obstruction by measurement of selective
      creatinine clearance (CCr), selective renographic clearance (RC), and renal
      resistive index. Sham group underwent sham surgery at 4 and 32 weeks and
      evaluated as the other 2 groups. RESULTS: Sham surgery showed no significant
      effect on any of the evaluated parameters. Compared with the control, losartan
      saved reduction in CCr by 11% and RC by 20% of the basal value by the end of the
      fourth week of obstruction, respectively. Moreover, compared with the control,
      losartan enhanced regain of CCr by 26% and RC by 26% also of the basal value at
      32 weeks after relief of fourth week obstruction, respectively. In addition, the
      increase in renal resistive index was significantly less in the losartan group.
      CONCLUSION: Losartan decreases the deterioration of renal function in PUO and
      enhances recoverability of renal function after relief of obstruction.

PMID- 19854475
TI  - Emphysematous cystitis.
AB  - We present the case of a 57-year-old man with emphysematous cystitis. The patient
      presented with a complaint of several days of lower abdominal pain and gross
      hematuria. Work-up included an abdominal CT scan that revealed gas within the
      urinary bladder wall, and cystoscopy confirmed diffuse submucosal emphysema
      throughout the bladder. The patient was treated conservatively with broad
      spectrum antibiotics, with prompt resolution of both symptoms and radiographic
      findings. Emphysematous cystitis is a rare clinically entity, more commonly seen
      in diabetic, immunocompromised patients. A conservative treatment approach using
      antibiotics and bladder catheterization is typically successful, with a
      complication rate of only 18.8%.

PMID- 19854476
TI  - Intractable voiding dysfunction in children with normal spinal imaging:
      predictors of failed conservative management.
AB  - OBJECTIVES: To identify the factors that might predict which individuals
      ultimately fail to resolve voiding symptoms by analyzing their presenting
      symptoms and video-urodynamic findings. Older children with intractable voiding
      dysfunction and no evidence of neurologic abnormality, who are recalcitrant to
      medical treatment, pose a management challenge. METHODS: The charts of
      neurologically normal children with intractable voiding dysfunction, who had
      fluorourodynamic studies and normal lumbosacral magnetic resonance imaging, were
      reviewed. A database was created that included the urodynamics, presenting
      urinary symptoms, presence of soiling or constipation, age at onset of symptoms,
      cystogram and bladder ultrasound findings, and treatments given. Long-term follow
      up was determined from chart review (all patients) or by a mailed survey (15
      patients). Patients without symptoms and off medication were defined as normal.
      RESULTS: A total of 50 children met the criteria mentioned earlier in the text,
      presented at a mean age of 9.4 years (range, 3.8-17.3) and were followed up for a
      mean of 4 years (range, 1-11) from their initial urodynamic evaluation. Of them,
      33 (66%) remained symptomatic and 1 (34%) normalized. A total of 31 were found to
      have uninhibited bladder contractions (UBCs) with daytime wetting, of which 24
      (77.4%) failed to normalize (P = .037). All 9 with UBCs and detrusor-sphincter
      dyssynergia remained symptomatic (P = .02). CONCLUSIONS: The majority failed to
      resolve their voiding symptoms. Children who presented with daytime wetting, UBC,
      and detrusor-sphincter dyssynergia were the most likely to remain symptomatic.
      Patients with these characteristics might be considered for more aggressive
      alternative therapies, after a period of medical management.

PMID- 19854477
TI  - Relationship between prostate-specific antigen and hematocrit: does hemodilution
      lead to lower PSA concentrations in men with a higher body mass index?
AB  - OBJECTIVES: To examine whether a lower hematocrit was associated with a lower
      prostate-specific antigen (PSA), when stratifying by body mass index (BMI) in
      healthy men. PSA test is widely used in screening for prostate cancer. Many
      studies have found that PSA levels inversely correlate with BMI. It remains
      unclear whether hemodilution causes this inverse relationship. METHODS: We
      investigated 19,367 men who visited a hospital for a routine health checkup in
      2007. We obtained information on age, BMI, PSA, hematocrit, and smoking status.
      BMI was categorized as < 18.5, 18.5-22.0, 22.0-25.0, 25.0-30.0, and > or = 30.0
      kg/m(2). RESULTS: In all subjects, older age and lower BMI were weakly correlated
      with a higher PSA (r = 0.20, P <.001 and r = -0.05, P <.001, respectively). A
      multiple regression model for predicting PSA was constructed using age, current
      smoking status, and hematocrit for each BMI category. After controlling for age
      and smoking, PSA increased significantly with increasing hematocrit in
      participants with BMIs of 18.5-30 kg/m(2) (all P <.001). For example, in men with
      a BMI of 22-25 kg/m(2), slight increases (1.4% increase; 95% confidence interval,
      1.0%-1.9%) were observed in PSA with a 1-unit increase in hematocrit.
      CONCLUSIONS: In healthy men with a BMI of 18.5-30 kg/m(2), a lower hematocrit was
      significantly associated with a lower PSA. Hemodilution may explain the lower PSA
      levels observed in men with a higher BMI, resulting in an inverse relationship
      between BMI and PSA.

PMID- 19854478
TI  - Renal masses herniating into the hilum: technical considerations of the "ball
      valve phenomenon" during nephron-sparing surgery.
AB  - OBJECTIVES: To describe our technique to recognize and resect renal tumors "ball
      valving" into the sinus. Partial nephrectomy (PN) offers a functional advantage
      over radical nephrectomy for many cases of localized renal cell carcinoma.
      However, PN is underutilized particularly in anatomically challenging cases.
      Often unrecognized is the tendency for central renal tumors to herniate into the
      renal sinus. METHODS: From our prospective kidney cancer database, we identified
      36 patients who underwent open, laparoscopic, or robotic PN for solitary
      localized renal cell carcinoma herniating into the renal sinus. RESULTS: Axial
      and reformatted radiographs were reviewed for all renal hilar lesions.
      Intraoperative techniques include hilar dissection, establishment of a sinus
      plane allowing tumor and parenchymal retraction, reduction of the tumor out of
      the sinus, resection, and repair. Mean preoperative lesion size was 3.8 cm.
      Indications for PN included 15 of 36 (42%) absolute, 13 of 36 (36%) relative, and
      2 of 36 (6%) reoperative PN. No procedure was converted to radical nephrectomy.
      Of the 36 PN, 5 (14%) were performed using a minimally invasive approach and no
      minimally invasive surgery procedures were converted to open. No patient required
      renal replacement. CONCLUSIONS: Recognition of the tendency for hilar masses to
      herniate or "ball-valve" into the renal sinus is essential for effective PN of
      central tumors. By using our technique, we have demonstrated success in nephron
      sparing surgery with minimal intraoperative complications and favorable
      postoperative outcomes in patients with central tumors herniating into the renal
      sinus.

PMID- 19854479
TI  - The effects of severity of urine leakage on quality of life in Hispanic, white,
      and black men and women: the Boston community health survey.
AB  - OBJECTIVES: To investigate the relationship between the severity of urine leakage
      and quality of life (QOL) in men and women of different race/ethnicity. METHODS:
      An epidemiologic survey was conducted with a population-based random sample of
      3202 women and 2301 men (1767 black, 1877 Hispanic, 1859 white) aged 30-79 years
      in Boston, MA. Severity of leakage was based on frequency and amount by the
      Sandvik Severity Scale. QOL was measured with physical and mental component
      summaries of Medical Outcomes Study Short Form-12. Covariates included
      race/ethnicity, age, socioeconomic status, urinary incontinence risk factors, and
      comorbidities. Analysis included multivariate linear regression modeling by
      gender. RESULTS: Urine leakage, most of which was mild or moderate, was reported
      in 30% of women and 18% of men. Women (5.1%) were more likely than men (0.9%) to
      report severe leakage. In multivariate analysis, as severity of leakage
      increased, both components of QOL declined, with decreases in scores of 7-8
      points for men (P < or = .001 for each) and 4-6 points (P < .05 and P = .001,
      respectively) for women. Severe leakage was associated with a greater decline in
      QOL than that observed for most other comorbidities considered. The effect of
      urine leakage on QOL was similar among racial and ethnic groups. CONCLUSIONS:
      Urine leakage impairs QOL for both men and women, with no evidence of different
      effects by racial/ethnic group. Leakage has clinically significant effects on
      physical health-related QOL for men and on mental health QOL for both men and
      women.

PMID- 19854480
TI  - Neonatal testicular infarction--possibly due to compression of the umbilical
      cord?
AB  - Neonatal testicular infarction is a rare occurrence. We report on a newborn
      infant with bilateral testicular infarction. At birth, the uncut umbilical cord
      ran taut between the thighs making a complete loop around the genitals,
      compressing the testes. At the age of 6 hours, because of increasing agitation
      and the beginnings of scrotal discoloration, the infant was operated on, showing
      a bilateral testicular infarction potentially induced by strangulation of the
      twisted umbilical cord. Here, we discuss the clinical findings of neonatal
      testicular infarction and give advice as to the management of this serious
      complication with regard to the available published data.

PMID- 19854481
TI  - Renal cell carcinoma associated with Xp11.2 translocations, report of a case.
AB  - Renal cell carcinomas (RCCs) associated with Xp11.2 translocations (Xp11.2
      translocation RCCs) are rare and occur predominantly in children and adolescents.
      A case of such tumor in a 12-year boy is reported. Grossly the cut surface of the
      ill-defined mass was polychromatic, containing areas of hemorrhage and necrosis.
      Microscopically, the tumor was composed of epithelioid cells with clear to weakly
      eosinophilic cytoplasm arranged in nested, alveolar, and pseudopapillary
      formations. Immunohistochemically, the neoplastic cells were positive for
      transcription factor E3 and CD10. We concluded that this case was an Xp11.2
      translocation RCC.

PMID- 19854482
TI  - Characteristics of autonomic nervous system activity in men with lower urinary
      tract symptoms (LUTS): analysis of heart rate variability in men with LUTS.
AB  - OBJECTIVES: To identify the difference in autonomic nervous dysfunction activity
      in men between voiding symptom-predominant lower urinary tract symptoms (LUTS)
      and storage symptom-predominant LUTS. METHODS: A total of 39 men with LUTS (mean
      age 56.9 +/- 8.96 years) and 23 healthy men (mean age 57.0 +/- 1.76 years) were
      included in the present study. Seven questions numbered Q1 to Q7 in the order of
      appearance in International Prostate Symptom Score were divided into 2 clusters:
      one with Q1, Q3, Q5, and Q6 and the other with Q2, Q4, and Q7, representing
      voiding and storage symptoms, respectively. Patients were divided into either
      voiding symptom-predominant group, if mean voiding symptom score, defined as (Q1
      + Q3 + Q5 + Q6)/4, is bigger than mean storage symptom score, defined as (Q2 +Q4
      + Q7)/3, or storage symptom-predominant group otherwise. We measured and compared
      parameters of heart rate variability between men with LUTS and healthy normal
      subjects. We also compared heart rate variability of men between storage symptom
      predominant LUTS and voiding symptom-predominant LUTS. RESULTS: On frequency
      domain analysis, there was evidence of decreased high frequency (HF) in patients
      with LUTS (P <.05). In comparison of autonomic nervous dysfunction activity in
      LUTS patients, men with voiding symptom-predominant LUTS had relatively increased
      ratio of low frequency and HF than what was observed in men with storage symptom
      predominant LUTS. CONCLUSIONS: Patients with LUTS exhibited decreased HF
      indicated that they may have had some disease or imbalance in the autonomic
      nervous system, which may distinguish LUTS patients from healthy men. Also,
      patients with voiding symptom-predominant LUTS had relatively increased
      sympathetic activity than storage symptom-predominant LUTS patients.

PMID- 19854483
TI  - Comparison of local anesthetic effects of tramadol with prilocaine during
      circumcision procedure.
AB  - OBJECTIVES: To compare the local anesthetic effects of tramadol hydrochloride
      with prilocaine for circumcision procedure. METHODS: This study included 40
      patients with American Surgical Association-I scores. Patients were randomly
      allocated to receive either 5% tramadol (2 mg/kg) plus adrenaline (0.0125/mL)
      (group 1, n = 20) or 2% prilocaine plus adrenaline (0.0125/mL) (group 2, n = 20).
      The degree of burning sensation and pain at the injection site were documented.
      Sensory block was assessed 1 minute after injection and the patients were asked
      to grade touch and pinprick sensation. Five minutes after drug administration,
      incision was performed and intensity of pain, felt by the patient was evaluated
      on a 4-point scale (0-3). Pain at the injection site and local skin reactions
      were also recorded. RESULTS: Mean ages were 9.7 and 10.3 years for groups 1 and
      2, respectively. Mean duration of surgery was 19.6 minutes. In control visit, 2
      of 20 (10%) in group 1 and 10 of 20 (50%) children in group 2 reported extra need
      for oral ibuprofen (P <.05). First analgesic medication time was 9.5 (+/- 2.1)
      hours in group 1 and 8.7 (+/- 3.1) hours in group 2 (P >.05). Total postoperative
      ibuprofen consumptions were 10 and 50 mg for groups 1 and 2, respectively (P
      <.05). CONCLUSIONS: A combination of tramadol 5% plus adrenaline can provide a
      safe and effective local anesthesia during circumcision procedure and
      postoperative period in children.

PMID- 19854484
TI  - Analysis of continence rates following robot-assisted radical prostatectomy:
      strict leak-free and pad-free continence.
AB  - OBJECTIVES: To propose a strict and specific definition of continence (leak-free
      and pad-free [LFPF]) and apply it to robot-assisted radical prostatectomy (RARP)
      outcomes on the basis of University of California-Los Angeles-Prostate Cancer
      Index (UCLA-PCI), as postprostatectomy incontinence is not well defined. METHODS:
      A single-institution RARP database was reviewed concerning continence variables
      prospectively recorded by the UCLA-PCI. Specific responses to urinary function
      and continence items were reviewed at baseline and 1, 3, 6, 12, and 24 months
      after surgery. RESULTS: From February 2003 to September 2007, a total of 1005 of
      1500 RARP patients had data available for review. At baseline, only 73% of these
      patients were LFPF. This decreased to 4%, 9%, 17%, 24%, and 28% at 1, 3, 6, 12,
      and 24 months after surgery, respectively. Applying less strict definitions, at
      24 months, 68% of patients reported no pad use and 90% of patients reported no
      pad use or the use of a security pad. When stratified by baseline LFPF status,
      patients not LFPF at baseline had higher baseline international prostate symptom
      score scores, lower urinary function scores, lower urinary bother scores, and
      larger prostate weights. Patients LFPF at baseline disproportionately regained
      LFPF continence starting 6 months after surgery compared with those not LFPF at
      baseline: 20% vs 9% (P = .005), 27% vs 15% (P = .0009), and 33% vs 15% (P =
      .0146) at 6, 12, and 24 months, respectively. CONCLUSIONS: A strict definition of
      urinary continence results in more conservative postoperative outcomes.
      Preoperative LFPF status can be predictive of postoperative LFPF continence.
      However, only one-third of patients LFPF at baseline returned to LFPF at 24
      months.

PMID- 19854485
TI  - Serum level of clusterin and its density in men with prostate cancer as novel
      biomarkers reflecting disease extension.
AB  - OBJECTIVES: To assess whether the serum level of clusterin and its density could
      be used as novel biomarkers of prostate cancer. METHODS: Sera were obtained from
      380 patients with prostate cancer and 120 with benign prostatic hyperplasia.
      Serum clusterin level was measured by a sandwich enzyme immunoassay, and
      clusterin density, which was determined by dividing the serum clusterin level by
      the prostate volume, was also calculated. These findings were analyzed with
      respect to several clinicopathologic factors. RESULTS: The mean serum level of
      clusterin in prostate cancer patients was significantly higher than that in the
      benign prostatic hyperplasia group. Both the serum clusterin level and clusterin
      density in prostate cancer patients were significantly associated with major
      prognostic factors other than biopsy Gleason score. Of the 380 prostate cancer
      patients, 162 underwent radical prostatectomy and pelvic lymphadenectomy, and 104
      and 58 were diagnosed as having organ-confined and extraprostatic diseases,
      respectively. The clusterin density in patients with organ-confined disease was
      significantly higher than that in patients with extraprostatic disease; however,
      there was no significant difference in the serum clusterin level between these 2
      groups. Furthermore, biochemical recurrence-free survival in patients with
      elevated clusterin density was significantly lower than that in patients with
      normal density. CONCLUSIONS: These findings suggest that serum clusterin level
      and its density could serve as a useful practical adjuncts to conventional
      parameters for estimating the extension of prostate cancer.

PMID- 19854486
TI  - Correlation of thermocouple data with voiding function after prostate
      cryoablation.
AB  - OBJECTIVES: To identify possible correlations of thermocouple recorded data with
      altered postoperative voiding function after prostate cryosurgery. METHODS: A
      retrospective analysis of the records of 58 patients treated with prostate
      cryoablation from October 2005 through April 2009 was conducted. Multivariate
      analysis of patient age, presenting prostate-specific antigen level, Gleason
      score, clinical T stage, prostate volume, maximum low temperature thermocouple
      recordings, history of radiation and or hormonal therapy, were studied as
      possible correlative factors for altered postoperative voiding function. RESULTS:
      Of 58 patients, 22 (37.9%) manifested postcryoablation urgency and frequency (n =
      13) requiring medical therapy or retention (n = 9). On multivariate analysis, age
      (P = .037) and an external sphincter temperature < or = 23 degrees C (P = .012)
      were associated with voiding frequency, urgency, or retention (odds ratio = 6.26,
      95% CI: 1.62-24.16), whereas anterior rectal wall temperature (Denon) was weakly
      associated (P = .079). CONCLUSIONS: Thermocouple data provide an objective means
      of assessing cryosurgical outcomes. This is the first report of a correlation of
      such data to post-treatment voiding function. A total of 37.9% of patients
      experienced urgency and/or frequency or urinary retention after cryoablation of
      the prostate for localized disease. Older age and external sphincter temperature
      < or = 23 degrees C were statistically significant predictors of these events.
      The data suggest that limiting the degree of freezing at the external sphincter
      may decrease procedure related morbidity. Further study is warranted to better
      delineate temperature-related data on treatment outcomes.

PMID- 19854487
TI  - Sensory perception thresholds in men with chronic pelvic pain syndrome.
AB  - OBJECTIVES: To compare sensory thresholds in different nerve-fiber types in men
      with chronic pelvic pain syndrome (CPPS) and healthy controls, using thermal
      sensory testing and measuring current perception thresholds (CPT). METHODS: We
      enrolled 22 men with CPPS and 20 healthy control participants. We determined the
      thermal sensory perception thresholds of C and Adelta nerve fibers on the
      perineum and left posterior thigh. To test CPT, we used sine wave electrical
      stimulation at 5, 250, and 2000 Hz, resulting in the selective depolarization of
      small unmyelinated C fibers, small myelinated Adelta, and large myelinated Abeta
      fibers, respectively. We bilaterally tested the hypothenar surface of the palms,
      medial parts of soles, midshaft of penis, and 1 site in the midperineum, for a
      total of 7 sites. RESULTS: The mean age of men with CPPS was similar to that of
      controls [42.8 (standard deviation, 9.4) and 40.4 (standard deviation, 13.2)
      years, respectively, P = .548]. There was no significant difference between the 2
      groups for thermal perception thresholds in both the perineum and left thigh (P
      >.05). There was also no difference between the 2 groups for CPT values of all 3
      frequencies of stimuli in each area tested (P >.05 for all comparisons).
      CONCLUSIONS: The absence of sensory threshold differences between men with CPPS
      and controls, with either thermal stimulation of C and Adelta fiber afferents or
      electrical stimulation of C, Adelta, and Abeta fiber afferents, discounts the
      existence of a peripheral neuropathy as a cause for pain in men with CPPS.

PMID- 19854488
TI  - Impact of prior urethral manipulation on outcome of anastomotic urethroplasty for
      post-traumatic urethral stricture.
AB  - OBJECTIVE: To determine the impact of earlier urethral interventions on the
      outcomes of anastomotic urethroplasty in post-traumatic stricture urethra.
      METHODS: From October 1995 to March 2008, a total of 58 patients with post
      traumatic posterior urethral stricture underwent anastomotic urethroplasty.
      Eighteen patients had earlier undergone urethral intervention in the form of
      urethrotomy (3), endoscopic realignment (7), or open urethroplasty (8). Success
      was defined as no obstructive urinary symptoms, maximum urine flow rate > or = 15
      mL/s, normal urethral imaging and/or urethroscopy, and no need of any
      intervention in the follow-up period. Patients who met the above objective
      criteria after needing 1 urethrotomy following urethroplasty were defined to have
      satisfactory outcome and were included in satisfactory result rate along with
      patients who had a successful outcome. Results were analyzed using unpaired t
      test, chi-square test, binary logistic regression, Kaplan-Meier curves, and log
      rank test. RESULTS: Previous interventions in the form of endoscopic realignment
      or urethroplasty have significant adverse effect on the success rate of
      subsequent anastomotic urethroplasty for post-traumatic posterior urethral
      strictures (P <.05). Previous intervention in the form of visual internal
      urethrotomies (up to 2 times) did not affect the outcome of subsequent
      anastomotic urethroplasty. Length of stricture and age of patient did not predict
      the outcome in traumatic posterior urethral strictures in logistic regression
      analysis. CONCLUSIONS: Previous failed railroading or urethroplasty significantly
      decrease the success of subsequent anastomotic urethroplasty. Hence, a primary
      realignment or urethroplasty should be avoided in suboptimal conditions and the
      cases of post-traumatic urethral stricture should be referred to centers with
      such expertise.

PMID- 19854489
TI  - Port-site hernias occurring after the use of bladeless radially expanding
      trocars.
AB  - OBJECTIVES: To compare and review the incidence of port-site hernias after use of
      bladeless radially dilating trocars after noticing a unique hernia entity
      developing in some patients. A review of the relevant published data is
      presented. METHODS: We retrospectively identified patients who were diagnosed or
      treated for postoperative hernias at our institution between 2004 and 2007 using
      a departmental morbidity database. All patients had laparoscopic urologic surgery
      for malignant conditions using bladeless radially dilating trocars. RESULTS: Of
      1055 consecutive patients who underwent laparoscopic urologic oncology surgery
      between 2004 and 2007, a total of 7 patients (0.66%) were identified with trocar
      site hernias. All hernias occurred using 12-mm bladeless radially dilating
      trocars without fascial closure. All hernias were confirmed by computed
      tomography of the abdomen and 6 by surgical findings. Of the 7 patients, 4 had an
      intrafascial incisional hernia; the small bowel herniated through a defect in the
      transversalis and internal oblique fasciae, but the external oblique fascia was
      intact. The intrafascial hernias were not evident on physical examination owing
      to an intact external oblique fascia. CONCLUSIONS: While rare, trocar-site
      herniation after use of bladeless radially dilating trocars is a potentially
      serious complication of laparoscopic surgery. A large proportion of these may be
      partial-wall or intrafascial hernias. It is important to increase awareness among
      laparoscopic surgeons of the possibility of intrafascial incisional hernias, as
      physical findings are subtle and early computed tomography diagnosis is necessary
      for timely surgical intervention.

PMID- 19854490
TI  - Percutaneous nephrolithotomy: nephrostomy or tubeless or totally tubeless?
AB  - OBJECTIVES: To compare the feasibility and morbidity of tubeless, totally
      tubeless, and standard percutaneous nephrolithotomy (PNL) with nephrostomy tube
      in a single center with selected patient population. METHODS: Between July 2006
      and February 2008, PNL was performed in 176 patients in this retrospective study.
      Patients with no serious bleeding or perforation in the collecting system during
      the operation, stone-free status, or clinically insignificant residual fragments
      (<4 mm) at the end of the procedure and patients with no more than one access
      were enrolled in the study. Patients were categorized into 3 groups. In group 1
      (n = 43), no nephrostomy or ureter catheters were placed after PNL (totally
      tubeless group); in group 2 (n = 41), no nephrostomy catheter was placed but
      antegrade J-stent was used (tubeless group), and in group 3 (n = 92), standard
      nephrostomy catheters were placed (standard group). Three groups were compared
      with respect to age, stone volume, postoperative hemoglobin change, transfusion
      rate, operation time, analgesic requirement, hospitalization time, and
      complication rates. RESULTS: No significant differences were found in mean stone
      volume, operation time, transfusion rates, and hemoglobin level change between
      the groups. However, hospitalization time and the amount of narcotic analgesic
      required were significantly higher in group 3 compared with the other groups (P
      <.05). Complications were observed in 2 (4.6%), 3 (7.3%), and 7 (7.6%) patients
      in groups 1, 2, and 3, respectively (P = .738). CONCLUSIONS: In patients with no
      major intraoperative bleeding and calyceal perforation, tubeless approach is safe
      with decreased analgesia requirement and hospital stay.

PMID- 19854491
TI  - Resistive index: a newly identified predictor of outcome of transurethral
      prostatectomy in patients with benign prostatic hyperplasia.
AB  - OBJECTIVE: To examine the usefulness of several preoperative parameters obtained
      through transrectal ultrasonography in predicting the outcome of transurethral
      resection of the prostate (TURP). METHODS: A total of 572 men aged 51-85 years
      scheduled to undergo TURP for benign prostatic hyperplasia were prospectively
      enrolled, and 560 were ultimately evaluated. We preoperatively assessed
      International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum
      urinary flow rate (Q(max)), and postvoid residual urine volume (PVR), and
      measured total prostate volume (TPV), transition zone (TZ) index, and resistive
      index (RI) using transrectal ultrasonography. To compare the usefulness of the
      latter 3 indices, we calculated the area under the receiver operating
      characteristic (ROC) curve for each index and for IPSS. RESULTS: IPSS (total,
      postmicturition symptoms, storage symptoms, voiding symptoms), QOL score, Q(max),
      and PVR were significantly improved after TURP. Significant differences between
      the effective and noneffective groups were observed with regard to age, IPSS
      (total, postmicturition symptoms, storage symptoms, voiding symptoms), QOL score,
      TPV, TZ index, RI, Q(max), and PVR. The area under the ROC curve was 0.663 for
      IPSS, 0.691 for TPV, 0.719 for the TZ index, and 0.845 for the RI. CONCLUSIONS:
      The RI is a useful predictor of an effective outcome after TURP in patients with
      benign prostatic hyperplasia and may be useful for determining suitability for
      surgical intervention.

PMID- 19854492
TI  - Systematic review and meta-analysis of transurethral resection of the prostate
      versus minimally invasive procedures for the treatment of benign prostatic
      obstruction.
AB  - Emerging minimally invasive procedures for the treatment of patients with benign
      prostatic obstruction may have advantages over transurethral resection of the
      prostate (TURP). We performed a systematic literature review and meta-analysis of
      randomized trials published upto April 2008 comparing TURP with photoselective
      vaporization, holmium laser ablation, and bipolar TURP. A total of 38 articles
      reporting results from 21 trials were included (photoselective vaporization = 3;
      holmium laser ablation = 1; bipolar TURP = 17). An assessment of perioperative
      and postoperative outcomes up to 12 months indicates benefits for these
      procedures. However, long-term follow-up and stronger methodological quality of
      the evidence is required to assess the long-term durability of the technologies.

PMID- 19854493
TI  - Changes in gender distribution of urinary stone disease.
AB  - OBJECTIVES: To explore using population-based data the extent to which gender
      specific rates of stone disease are changing. Historically, stone disease has
      been more common among men than women. However, differential changes in dietary
      intake patterns, fluid intake, and obesity in men and women may cause shifts in
      stone disease incidence and prevalence. METHODS: The State Ambulatory Surgical
      Database and the State Inpatient Databases were queried for procedures related to
      renal colic or urolithiasis. Population-based rates of utilization were
      calculated for the years 1998-2004 by gender. Poisson regression models were fit
      to measure changes in utilization rates over time. RESULTS: Of the 107,411
      discharges for stone disease, 41,272 (38%) occurred in women. Service utilization
      increased in both men and women (86.6-105.5 and 42.5-64.4 per 100,000; P <.01 in
      both). However, the growth rate in women outpaced men (P <.01). Rates of
      outpatient (57.2-65.8 and 27.0-38.9 per 100,000; P <.01) and ambulatory surgery
      center utilization (6.4-17.7 and 2.9-9.3 per 100,000 men and women; P <.01)
      increased significantly in men and women, but inpatient utilization only
      increased in women (12.5-16.3 per 100,000; P <.01). CONCLUSIONS: Resource
      utilization for stone disease continues to increase. Most of this increase
      appears to be due to an increase in disease among women. Increasing obesity,
      dietary changes, or decreased fluid intake may be contributing to the rapid
      increase in stone disease treatments in women.

PMID- 19854494
TI  - Durability of the next-generation flexible fiberoptic ureteroscopes: a randomized
      prospective multi-institutional clinical trial.
AB  - OBJECTIVES: To evaluate the durability of 4 next-generation flexible
      ureteroscopes in a randomized, multi-institutional, prospective study. METHODS:
      Patients at 3 institutions were randomized to 1 of 4 flexible ureteroscopes: the
      Wolf Viper, Olympus URF-P5, Gyrus-ACMI DUR-8 Elite (DUR-8E), and Stryker
      FlexVision U-500. Each center used 1 scope from each manufacturer until it needed
      major repair (primary endpoint). Intraoperative data included total time of use,
      number of scope insertions through an access sheath, working time in the lower
      pole, number of insertions and total time for accessory instrumentation in the
      working channel, number of laser insertions through the working channel, and
      total laser energy used. RESULTS: A total of 175 patients were randomized. The
      DUR-8E experienced early catastrophic failure (< or = 10 cases) at all 3 sites;
      however, this also occurred at 1 site each for the Stryker and Wolf scopes. The
      DUR-8E required major repair after the fewest average number of cases (5.3), the
      lowest average total time of usage (108 minutes), the fewest insertions through
      an access sheath (20.3), the shortest duration of laser firing (31.3 minutes),
      and the shortest instrument in the working channel time (224.7 minutes). As such,
      due to variation in durability within manufacturers, no differences could be
      demonstrated. Visibility ratings for the Wolf iper were significantly better than
      the DUR-8E (P = .034) and the Flexvision (P = .038). CONCLUSIONS: The Wolf Viper,
      Olympus URF-P5, and Stryker Flexvision U-500 flexible ureteroscopes seem
      comparable with regard to durability. However, larger prospective registry-based
      studies are needed to document significant differences between them.

PMID- 19854495
TI  - Epigenetic therapies for chemoresensitization of epithelial ovarian cancer.
AB  - Epigenetic drugs have been shown to enhance gene expression and drug sensitivity
      in ovarian cancer cell lines and animal models. Based on promising preclinical
      studies, DNA methylation inhibitors in combination with existing chemotherapeutic
      agents have the potential for overcoming acquired drug resistance, laying the
      foundation for this specific class of epigenetic drug in ovarian cancer clinical
      trials. The recent completion of phase I trials of decitabine has yielded
      important information on dosing schedules and biological endpoints for evaluating
      patient responses. In addition, epigenetic drug effects on pharmacodyamic targets
      are beginning to emerge, and predictive epigenetic biomarkers and next generation
      epigenome therapeutics are being developed for application in clinical settings
      for ovarian cancer patients.

PMID- 19854496
TI  - Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells
      stimulated by oxidized low density lipoprotein.
AB  - OBJECTIVES: We previously observed an association between ovarian cancer outcome
      and statin use and hypothesized lipoproteins have direct effects on ovarian
      cancer proliferation. Here we investigate the direct effects of low density
      lipoprotein (LDL) and oxidized LDL (oxLDL) on proliferation and the inhibitory
      effects of fluvastatin and a liver X receptor (LXR) agonist. METHODS: The effects
      of LDL, oxLDL, the LXR agonist TO901317, fluvastatin and cisplatin on cellular
      proliferation were determined using MTT assays. LXR pathway proteins were assayed
      by immunoblotting. Cytokine expression was determined by antibody array. RESULTS:
      Concentrations of oxLDL as small as 0.1 microg/ml stimulated CAOV3 and SKOV3
      proliferation, while LDL had no effect. TO901317 inhibited the proliferation of
      CAOV3, OVCAR3 and SKOV3 cells stimulated by oxLDL. Fluvastatin inhibited oxLDL
      mediated proliferation of CAOV3 and SKOV3. Cardiotrophin 1 (CT-1) was mitogenic
      to CAOV3 and SKOV3, was induced by oxLDL, and was reversed by TO901317. OxLDL
      increased cisplatin IC50s by 3.8 microM and > 60 microM for CAOV3 and SKOV3
      cells, respectively. The LXR pathway proteins CD36, LXR, and ABCA1 were expressed
      in eight ovarian carcinoma cell lines (A2780, CAOV3, CP70, CSOC882, ES2, OVCAR3,
      SKOV3). CONCLUSIONS: OxLDL reduced ovarian carcinoma cell chemosensitivity and
      stimulated proliferation. These effects were reversed by LXR agonist or
      fluvastatin. The LXR agonist also inhibited expression of the ovarian cancer
      mitogen CT-1. These observations suggest a biologic mechanism for our clinical
      finding that ovarian cancer survival is associated with statin use. Targeting LXR
      and statin use may have a therapeutic role in ovarian cancer.

PMID- 19854497
TI  - Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian
      cancer: evidence supporting a mesothelial-to-epithelial transition.
AB  - OBJECTIVE: Our objective was to characterize the expression and function of the
      miR-200 family of microRNAs (miRNA) in ovarian carcinogenesis. METHODS: We used
      qRT-PCR to examine expression of the miR-200 miRNA family and its predicted
      targets, the ZEB1 and ZEB2 transcriptional repressors, in primary cultures of
      normal cells from the surface of the ovary and in a panel of 70 ovarian cancer
      tissues and 15 ovarian cancer cell lines. We studied the mechanisms of regulation
      of miR-200 miRNAs and ZEB transcription factors in ovarian cells using 3' UTR
      luciferase reporters, promoter luciferase reporters and siRNAs. RESULTS: miR-200
      family members are expressed at low or negligible levels in normal ovarian
      surface cells and substantially increase in expression in ovarian cancer, whereas
      expression of ZEB1 and ZEB2 shows the opposite pattern. There is reciprocal
      repression between miR-200 family members and ZEB transcription factors, creating
      a double negative regulatory feedback loop resembling that reported in other
      cancer cell types. In contrast to epithelial cells from other sites, expression
      levels of miR-200 miRNAs and ZEB1/2 in cells from the ovarian surface are more
      consistent with a mesenchymal cell phenotype, potentially reflecting the
      mesothelial origin of the ovarian surface. CONCLUSION: Analysis of ovarian cancer
      tissues suggests that ovarian surface cells acquire a more epithelial miR-200
      ZEB1/2 phenotype as they undergo transformation, switching from a miR-200
      familyLOW and ZEB1/2HIGH state to a miR-200 familyHIGH and ZEB1/2LOW phenotype.
      Collectively, our data support the mesothelial-to-epithelial (Meso-E-T) model for
      development of ovarian cancers that arise from ovarian surface cells, as has been
      proposed previously on the basis of studies of protein markers.

PMID- 19854498
TI  - Perceived mattering to parents and friends for university students: a
      longitudinal study.
AB  - A multiple indicators multilevel (MIML) latent growth model was used to examine
      university students' (N=484) perceived mattering to mother, father, and friends
      over a three year period. The model was used to examine whether repeated
      measurements of perceived mattering remained invariant across time for all three
      referents, what the developmental trajectories looked like, and if the growth
      trajectories varied between gender groups and living arrangements. Temporal
      measurement invariance held for all three referents. Growth trajectories showed a
      significant declining slope for perceived mattering to mother only. Women
      perceived themselves as mattering to parents and friends more than men. Living
      arrangements were associated with mattering to friends but not mattering to
      parents.

PMID- 19854499
TI  - Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a
      phase 1 dose-escalation trial.
AB  - BACKGROUND: Gene therapy has the potential to reverse disease or prevent further
      deterioration of vision in patients with incurable inherited retinal
      degeneration. We therefore did a phase 1 trial to assess the effect of gene
      therapy on retinal and visual function in children and adults with Leber's
      congenital amaurosis. METHODS: We assessed the retinal and visual function in 12
      patients (aged 8-44 years) with RPE65-associated Leber's congenital amaurosis
      given one subretinal injection of adeno-associated virus (AAV) containing a gene
      encoding a protein needed for the isomerohydrolase activity of the retinal
      pigment epithelium (AAV2-hRPE65v2) in the worst eye at low (1.5 x 10(10) vector
      genomes), medium (4.8 x 10(10) vector genomes), or high dose (1.5 x 10(11) vector
      genomes) for up to 2 years. FINDINGS: AAV2-hRPE65v2 was well tolerated and all
      patients showed sustained improvement in subjective and objective measurements of
      vision (ie, dark adaptometry, pupillometry, electroretinography, nystagmus, and
      ambulatory behaviour). Patients had at least a 2 log unit increase in pupillary
      light responses, and an 8-year-old child had nearly the same level of light
      sensitivity as that in age-matched normal-sighted individuals. The greatest
      improvement was noted in children, all of whom gained ambulatory vision. The
      study is registered with ClinicalTrials.gov, number NCT00516477. INTERPRETATION:
      The safety, extent, and stability of improvement in vision in all patients
      support the use of AAV-mediated gene therapy for treatment of inherited retinal
      diseases, with early intervention resulting in the best potential gain. FUNDING:
      Center for Cellular and Molecular Therapeutics at the Children's Hospital of
      Philadelphia, Foundation Fighting Blindness, Telethon, Research to Prevent
      Blindness, F M Kirby Foundation, Mackall Foundation Trust, Regione Campania
      Convenzione, European Union, Associazione Italiana Amaurosi Congenita di Leber,
      Fund for Scientific Research, Fund for Research in Ophthalmology, and National
      Center for Research Resources.

PMID- 19854500
TI  - Promises and challenges of genetic therapy for blindness.

PMID- 19854501
TI  - Reproductive and life stage-specific effects of aqueous copper on the grass
      shrimp, Palaemonetes pugio.
AB  - Palaemonetes pugio exposed to copper (9 or 26 microg Cu(2+)/L) for a full life
      cycle were unable to produce viable embryos, precluding completion of the life
      cycle, despite no lethal effects on larval, juvenile, or adult life stages.
      Exposure to copper also resulted in a significant delay in larval development.
      When adults raised in copper were transferred to control seawater, they produced
      viable embryos, but larval output per clutch was reduced by 43% compared to
      clutches from females that had never been exposed to copper, suggesting reduced
      energetic allocation to reproduction. In acute exposures, adults exposed to
      copper for as little as three days were unable to produce viable embryos.
      Furthermore, exposure of control embryos to copper reduced hatching success by
      74%. The reduction in hatching success and energetic allocation to reproduction
      are unlikely to be completely responsible for the lack of larval production
      observed in pre-spawning exposures to copper, suggesting that copper may also
      inhibit processes before or during spawning and fertilization.

PMID- 19854502
TI  - Small intestine submucosa sponge for in vivo support of tissue-engineered bone
      formation in the presence of rat bone marrow stem cells.
AB  - The aim of the current study was to visualize new bone formed in vivo on a small
      intestine submucosa (SIS) sponge used as a tissue-engineered scaffold for the
      repair of damaged bone. The SIS sponge provided a three-dimensional pore
      structure, and supported good attachment and viability of rat bone marrow stem
      cells (rBMSCs). To examine bone regeneration, we prepared full-thickness
      bilateral bone defects in the rat crania, and then treated the defects with an
      implanted SIS sponge or PGA mesh without or with rBMSCs, or left the defects
      untreated. Bone defects were evaluated by micro-CT and histologically after 2 and
      4 weeks. Micro-CT demonstrated a trend toward a decrease in bone void in both the
      SIS sponge and SIS sponge/rBMSCs groups compared to the control and PGA mesh
      groups. At 4 weeks, bone formation in defects containing SIS sponge/rBMSCs was
      significantly greater than in all other groups. A histological analysis after 2
      and 4 weeks of implantation showed localized collagen and osteocalcin deposition
      on SIS sponges and SIS sponges with rBMSCs. These in vivo results indicate that
      the SIS sponge, implanted at bone-removal defects, facilitated bone regeneration.

PMID- 19854503
TI  - pH-sensitive carbonate apatite as an intracellular protein transporter.
AB  - The transfer of specific proteins into living cells to enable the regulation of
      cell function or the tracking of the intracellular distribution of proteins is a
      desirable objective for offering a potential alternative to gene therapy. Here,
      protein/carbonate apatite complexes were successfully fabricated for
      intracellular delivery of functional proteins since the carbonate apatite being
      highly water solubility under an acidic condition could easily be dissolved in
      endosomes following endocytosis, thus releasing the electrostatically associated
      proteins in cytoplasm. In this study, we characterized protein/carbonate apatite
      complexes as an intracellular protein delivery system and we checked
      intracellular delivery of proteins by carbonate apatite nanoparticles in vitro.
      Fluorescently-labeled bovine serum albumin as a model protein was effectively
      delivered into nearly 100% of HeLa cells by the simple addition of
      protein/carbonate apatite complexes to the cells. Confocal microscopic imaging
      suggested the endosomal release of protein delivered with carbonate apatite. And
      intracellularly delivered ss-galactosidase did not lose its enzymatic activity.
      These results suggested that intracellular delivery system of protein using pH
      sensitive carbonate apatite carrier with a very simple procedure will be a highly
      effective method to the biological and clinical researches.

PMID- 19854504
TI  - A guanidinylated bioreducible polymer with high nuclear localization ability for
      gene delivery systems.
AB  - Guanidinylated bioreducible polymer (GBP) was developed for gene delivery systems
      utilizing cellular penetrating ability of guanidine groups. GBP could retard pDNA
      from a weight ratio of 5 completely in agarose gel electrophoresis but pDNA was
      released from GBP polyplexes even at a weight ratio of 20 in reducing condition
      (2.5mm DTT) due to their biodegradation. GBP also could construct 200 nm-sized
      and positively charged (approximately 30 mV) polyplex nanoparticles with pDNA.
      The cytotoxicity of GBP was found to be minimal and GBP showed about 8 folds
      improved transfection efficiency than a scaffold polymer,
      poly(cystaminebisacrylamide-diaminohexane) (poly(CBA-DAH)) and even higher
      transfection efficiency than PEI25k in mammalian cell lines. Its high cellular
      uptake efficiency (96.1%) and strong nuclear localization ability for pDNA
      delivery due to the structural advantage of bioreducible polymer and guanidine
      groups were also identified, suggesting GBP is a promising candidate for
      efficient gene delivery systems.

PMID- 19854506
TI  - The stimulation of angiogenesis and collagen deposition by copper.
AB  - Copper is known to trigger endothelial cells towards angiogenesis. Different
      approaches have been investigated to develop vascularisation in biomaterials. The
      angiogenic and healing potential of copper ions in combination with two major
      angiogenic factors was examined. A 3D culture system in which, under stimulation
      by FGF-2 and to a lesser degree with VEGF, endothelial cells assembled into
      structures resembling to an angiogenic process was used. The combination of
      CuSO(4) with increasing doses of VEGF or FGF-2 enhanced the complexity of
      angiogenic networks in a significant manner. In vivo studies were also conducted
      by incorporating FGF-2 with CuSO(4) in a cylindrical collagen-based scaffold.
      CuSO(4) enhanced significantly the invasion of microvessel compared to control
      implants and to 20ng FGF-2+/-CuSO(4). Vascular infiltration was also
      significantly improved by combination of CuSO(4) with FGF-2, compared to FGF-2
      alone (0.2 and 1microg). Nevertheless, in comparison with CuSO(4) alone, there
      was a significant increase only with 1microg of FGF-2 combined with CuSO(4).
      Significantly, collagen fiber deposition was enhanced following the combinatory
      loading in comparison to that with FGF-2 alone but not with CuSO(4) only. Thus,
      copper associated with growth factors may have synergistic effects which are
      highly attractive in the fields of tissue engineering (e.g., bone) and
      biomaterials.

PMID- 19854505
TI  - Long-term biostability of self-assembling protein polymers in the absence of
      covalent crosslinking.
AB  - Unless chemically crosslinked, matrix proteins, such as collagen or silk, display
      a limited lifetime in vivo with significant degradation observed over a period of
      weeks. Likewise, amphiphilic peptides, lipopeptides, or glycolipids that self
      assemble through hydrophobic interactions to form thin films, fiber networks, or
      vesicles do not demonstrate in vivo biostability beyond a few days. We report
      herein that a self-assembling, recombinant elastin-mimetic triblock copolymer
      elicited minimal inflammatory response and displayed robust in vivo stability for
      periods exceeding 1 year, in the absence of either chemical or ionic
      crosslinking. Specifically, neither a significant inflammatory response nor
      calcification was observed upon implantation of test materials into the
      peritoneal cavity or subcutaneous space of a mouse model. Moreover, serial
      quantitative magnetic resonance imaging, evaluation of pre- and post-explant
      ultrastructure by cryo-high resolution scanning electron microscopy, and an
      examination of implant mechanical responses revealed substantial preservation of
      form, material architecture, and biomechanical properties, providing convincing
      evidence of a non-chemically or ionically crosslinked protein polymer system that
      exhibits long-term stability in vivo.

PMID- 19854507
TI  - Cloning and distribution of neuropeptide S and its receptor in the pig.
AB  - Neuropeptide S (NPS) precursor gene is present in most vertebrates. However, the
      genes of NPS and its receptor (NPSR), and their functions in the pig are
      currently not well understood. In order to clarify their physiological functions,
      it is essential to characterize in detail the distribution of NPS and NPSR. In
      this report, the cDNAs of NPS and NPSR were cloned and sequenced. Homology and
      phylogenetic analysis of NPS gene sequences were performed. The expression of NPS
      and NPSR mRNA in the pig was systemically investigated using semiquantitative
      reverse transcription polymerase chain reaction (RT-PCR), while the distribution
      of NPS was determined by immunohistochemistry. Our results demonstrated that the
      gene and predicted amino acid sequences of both NPS and NPSR were highly
      conserved. Phylogenetic analysis showed that NPS coding sequences from related
      species display high degrees of homology. NPS and NPSR mRNAs were widely
      expressed in various tissues of the pig. NPS mRNA was highly expressed in CNS,
      while NPSR mRNA was widely expressed in many tissues, with high expression in the
      hypophysis, endocrine tissues and glands. NPS protein also exhibited the
      different distribution in various organs. In the pig brain, NPS immunoreactive
      cells were mainly found in the diencephalon, pons and hypophysis, while
      immunoreactive fibres were widely distributed in the hypothalamus and olfactory
      bulb. In the peripheral organs, NPS immunoreactive cells were observed in the
      respiratory tract, alimentary tract, endocrine organs, genitourinary tract,
      lymphatic organs, muscle tissue, skin and skin appendages. By showing gene
      sequences and distribution of NPS and NPSR, these results suggest that NPS and
      NPSR in the pig might play important role in modulating a variety of
      physiological functions as in human and other animals. This research provided
      molecular and morphological data for further study of physiological function of
      NPS-NPSR system.

PMID- 19854508
TI  - Detection of exon 12 type A mutation of NPM1 gene in IMS-M2 cell line.
AB  - Nucleophosmin 1 (NPM1), a protein that shuttles between the nucleus and
      cytoplasm, is mostly located in nucleoli. This is a multifunctional
      phosphoprotein to which both tumor-suppressor and oncogenic functions have been
      attributed. Here, we have found the cell line with the type A NPM1 mutation and
      with the other genetic alterations including ETV6-NTRC fusion. It will provide a
      good in vitro model for bio-molecular studies of interaction of mutated NPM1 gene
      and other genetic abnormalities as well as a useful tool for developing new
      molecularly targeted drugs.

PMID- 19854509
TI  - Isolation of malignant B cells from patients with chronic lymphocytic leukemia
      (CLL) for analysis of cell proliferation: validation of a simplified method
      suitable for multi-center clinical studies.
AB  - BACKGROUND: Heavy water ((2)H(2)O) labelling of DNA enables the measurement of
      low-level cell proliferation in vivo, using gas chromatography/pyrolysis isotope
      ratio mass spectrometry (GC/P/IRMS), but the methodology has been too complex for
      widespread use. Here, we report a simplified method for measuring proliferation
      of malignant B cells in patients with chronic lymphocytic leukemia (CLL). DESIGN
      AND METHODS: Patients were labelled with (2)H(2)O for 6 weeks; blood samples were
      obtained at 0, 3, and 6 weeks during (2)H(2)O labelling and 9, 12, and 16 weeks
      thereafter. Bone marrow was sampled at week 6. Phlebotomy was performed at
      multiple, non-research clinical sites. CLL cells were isolated in a central
      laboratory, using a novel RosetteSep-based method; DNA labelling was analyzed by
      GC/P/IRMS. RESULTS: In 26 of 29 patients, CLL cell isolation resulted in > or
      =95% purity for malignant CD5+ B cells; in one patient, malignant cells expressed
      marginal levels of CD5, and in two others, further sorting of CD5hi malignant
      cells was required. Cell yields correlated with white blood cell counts and
      exceeded GC/P/IRMS requirements ( approximately 10(7) cells) >98% of the time;
      high-quality DNA labelling data were obtained. RosetteSep isolation achieved
      adequate CLL cell purity from bone marrow in only 64% of samples, but greatly
      reduced subsequent sort time for impure samples. CONCLUSION: This method enables
      clinical studies of CLL cell proliferation outside of research settings, using a
      shorter (2)H(2)O intake protocol, a minimal sampling protocol, and centralised
      sample processing. The CLL cell isolation protocol may also prove useful in other
      applications. (clinicaltrials.gov identifier: NCT00481858).

PMID- 19854510
TI  - A commentary on national child maltreatment surveillance systems: Examples of
      progress.

PMID- 19854511
TI  - The development and piloting of the ISPCAN Child Abuse Screening Tool-Parent
      version (ICAST-P).
AB  - OBJECTIVE: Child maltreatment is a problem that has longer recognition in the
      northern hemisphere and in high-income countries. Recent work has highlighted the
      nearly universal nature of the problem in other countries but demonstrated the
      lack of comparability of studies because of the variations in definitions and
      measures used. The International Society for the Prevention of Child Abuse and
      Neglect has developed instrumentation that may be used with cross-cultural and
      cross-national benchmarking by local investigators. DESIGN AND SAMPLING: The
      instrument design began with a team of expert in Brisbane in 2004. A large bank
      of questions were subjected to two rounds of Delphi review to develop the fielded
      version of the instrument. Convenience samples included approximately 120 parent
      respondents with children under the age of 18 in each of six countries (697
      total). RESULTS: This paper presents an instrument that measures parental
      behaviors directed at children and reports data from pilot work in 6 countries
      and 7 languages. Patterns of response revealed few missing values and
      distributions of responses that generally were similar in the six countries.
      Subscales performed well in terms of internal consistency with Cronbach's alpha
      in very good range (0.77-0.88) with the exception of the neglect and sex abuse
      subscales. Results varied by child age and gender in expected directions but with
      large variations among the samples. About 15% of children were shaken, 24% hit on
      the buttocks with an object, and 37% were spanked. Reports of choking and
      smothering were made by 2% of parents. CONCLUSION: These pilot data demonstrate
      that the instrument is well tolerated and captures variations in, and potentially
      harmful forms of child discipline. PRACTICE IMPLICATIONS: The ISPCAN Child Abuse
      Screening Tool - Parent Version (ICAST-P) has been developed as a survey
      instrument to be administered to parents for the assessment of child maltreatment
      in a multi-national and multi-cultural context. It was developed with broad input
      from international experts and subjected to Dephi review, translation, and pilot
      testing in six countries. The results of the Delphi study and pilot testing are
      presented. This study demonstrates that a single instrument can be used in a
      broad range of cultures and languages with low rates of missing data and moderate
      to high internal consistency.

PMID- 19854512
TI  - Safe drinking water: critical components of effective inter-agency relationships.
AB  - The paper supports the development of evidence-based emergency management
      frameworks of cooperation between agencies in the area of drinking water and
      public health, as part of developing the overall risk management culture within
      water utilities. We employed a qualitative research design to understand critical
      gaps in inter-agency relations that aggravated past drinking water and health
      incidents and from these identified determinants of effective relationships. We
      identified six critical institutional relationship components that were deficient
      in past incidents, namely proactivity, communication, training, sharing
      expertise, trust and regulation. We then analysed how these components are
      addressed by reputable water utilities and public health departments to develop
      positive examples of inter-agency cooperation. Control of different risks (e.g.
      public health, business, and reputation) resulting from drinking water incidents
      should employ a preventive framework similar to the multiple barrier approach for
      management of drinking water quality.

PMID- 19854513
TI  - Persistent organic pollutants in breast milk of mothers residing around an open
      dumping site in Kolkata, India: specific dioxin-like PCB levels and fish as a
      potential source.
AB  - Concentrations of persistent organic pollutants (POPs) such as polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated
      biphenyls (PCBs) and organochlorine pesticides were measured in human breast milk
      collected from mothers residing near an open dumping site and a reference site in
      Kolkata, India during 2004-2005. POPs were detected in all the human milk samples
      analyzed, suggesting that residents of Kolkata are widely exposed to these
      contaminants. Concentrations of dioxin-like PCBs in the samples from the dumping
      site were significantly higher than in the reference site samples, whereas no
      such difference was found for PCDDs and PCDFs. In addition, significantly higher
      concentrations of total PCBs were also observed in the samples from the dumping
      site than the reference site. Interestingly, concentrations of total and dioxin
      like PCBs in the breast milk of mothers from the dumping site significantly
      increased with the number of years of residence near the dumping site. These
      results indicate that significant pollution sources of PCBs are present in the
      dumping site of Kolkata and the residents living around are exposed to relatively
      higher levels of PCBs. When the residue levels of dioxins and related compounds
      in fish collected from ponds near the Kolkata dumping site and the reference site
      were measured, it was found that dioxin-like PCB and TEQ levels in fish from the
      dumping site were notably higher than those from the reference site. This result
      indicates that fish is a potential source of PCBs for residents living near the
      Kolkata dumping site.

PMID- 19854514
TI  - Natural history of open-angle glaucoma.
AB  - OBJECTIVE: This article, based on the Early Manifest Glaucoma Trial (EMGT),
      provides prospective natural history data on progression of glaucomatous field
      defects in 3 of the most common glaucoma types. DESIGN: Cohort of EMGT patients
      randomized to the untreated control group and followed up to the time of
      progression, when treatment could be initiated. PARTICIPANTS: We evaluated 118
      control patients: 46 with high-tension glaucoma (HTG), 57 with normal-tension
      glaucoma (NTG), and 15 with pseudoexfoliation glaucoma (PEXG). METHODS: Visual
      fields were tested every 3 months with the Humphrey 30-2 Full Threshold test
      program. MAIN OUTCOME MEASURES: Linear regression analyses of the perimetric mean
      deviation (MD) values were performed, and the rate of progression was defined as
      the regression coefficient in decibels per year. Percentages of progressed eyes
      and time to progression were determined using EMGT event-based predetermined
      progression criteria derived from Glaucoma Change Probability Maps. RESULTS: The
      median and interquartile rates of visual function loss were -0.40 (1.05) dB/year
      overall and -0.46 (1.61) in HTG, -0.22 (0.65) in NTG, and -1.13 (6.13) in PEXG.
      Thus, interpatient variability was large. Mean rates were considerably higher
      than medians: -1.08 dB/year overall, -1.31 in HTG, -0.36 in NTG, and -3.13 in
      PEXG. Differences in median visual function progression rates among groups were
      statistically significant (NTG vs. HTG, P = 0.003; PEXG vs. non-PEXG, P<0.001).
      Progression was considerably and significantly faster in older than in younger
      patients (P = 0.002). By 6 years, 68% of patients had progressed overall, 74% of
      those with HTG, 56% of those with NTG, and 93% of those with PEXG (P = 0.012).
      Median time to progression also differed considerably among groups: 19.5 months
      in PEXG, 44.8 months in HTG, and particularly 61.1 months in NTG (P<0.0001).
      CONCLUSIONS: In this 6-year follow-up study, the median untreated rate of
      progression corresponded to advancing from normal visual function to blindness in
      approximately 70 years, whereas on the basis of the mean rate, visual function
      would show the same deterioration in approximately 25 years. Large differences
      existed among patients and different glaucoma types, with PEXG progressing
      considerably faster than HTG, and NTG progressing at the lowest rate.

PMID- 19854515
TI  - The social contexts of depression during motherhood: a study of Explanatory
      Models in Vietnam.
AB  - BACKGROUND: Major depression is increasing world-wide, and is the fourth leading
      cause of the global disease burden. Depression is rarely diagnosed in primary
      care settings in Vietnam, and those afflicted usually only seek professional care
      when the illness has become very severe. Depressive disorders affecting mothers
      are an important cause of low birth-weight, childhood stunting, under nutrition
      and adverse mental development, and a study has shown a 33% prevalence of
      postnatal depression symptoms in Ho Chi Minh City. METHODS: The aim of this study
      was to elicit Illness Explanatory Models (EMs) of depression and postnatal
      depression from nine mothers and nine health workers. The study was conducted in
      a semi-rural area in Vietnam, and the EMs were elicited through semi-structured
      interviews where a case vignette of depression was used as the basis of
      questioning. RESULTS: The EMs elicited were predominantly somatosocial in nature
      and the mothers assigned a strong personal responsibility for care. Psychiatric
      treatment and care was seldom recommended. Lack of communication was described as
      an important factor concealing depression, and together with the lack of care
      seeking can be expected to impede effective treatment. LIMITATIONS: The results
      of this study cannot be generalised beyond the group studied, or the context of
      Ba Vi, though we believe that analytical generalisation to other contexts can be
      made. CONCLUSION (CLINICAL RELEVANCE): The results of this study highlight the
      importance of depression and postnatal depression being diagnosed in primary
      care, and of a cross-sectoral approach for the prevention of depression in
      Vietnam, which takes into account the social causation of depression in women.

PMID- 19854516
TI  - HOXA10 signals on the highway through pregnancy.
AB  - Implantation represents the remarkable synchronization between the development of
      the embryo and the differentiation of the endometrium. It depends on uterine
      dependent and embryo-specific events, which are critically and sequentially
      coordinated. A plethora of molecules have been identified which play major roles
      before and after embryo implantation. In recent years HomeoboxA10 (HOXA10) has
      emerged as one of the most promising candidates which regulate the events
      occurring in the maternal compartment for successful establishment of pregnancy.
      HOXA10 is a transcription factor that is crucial for development and patterning
      of the uterus during embryogenesis. In the adult endometrium, HOXA10 is expressed
      in a menstrual cycle dependent manner and it is regulated by ovarian steroid
      hormones and embryonic signals, HOXA10 is required for uterine receptivity and
      implantation, and is a key regulator of decidualization. In the decidua, HOXA10
      is involved in regulation of cell cycle and local immunomodulation. The present
      review summarizes the events that are regulated by HOXA10 in embryo implantation
      and decidualization.

PMID- 19854517
TI  - Early regulators in abortion and implications for a preeclampsia model.
AB  - This paper reports a summary of our comparative analysis of the uterine
      expression of interleukin-23 (IL-23), IL-27 and TWEAK in the CBA/J femalexDBA/2
      male mouse mating combination, a model of immune-mediated early pregnancy loss.
      Compared with the MHC-identical CBA/JxBALB/c mating combination, which yields
      successful pregnancies, immunohistochemistry and qPCR in uterine tissue showed an
      immediate post-mating IL-27 hyper-expression after mating with DBA/2 males. Intra
      uterine TWEAK expression was present in females mated with DBA/2 or Balb/c males
      from days 0.5 to 4.5 post-coitum (pc), peaking on day 0.5 pc together with
      uterine TNFalpha. In uteri of DBA/2 mated mice, TWEAK declined to almost
      undetectable levels on days 6.5-9.5 pc, a steeper drop than in BALB/c mated mice
      where TWEAK remained detectable. In both mating combinations, neutralisation of
      TWEAK by antibodies increased resorption rates, but surprisingly, so did IL-27
      neutralisation. The complement regulator mannan binding lectin-A (MBL-A), but not
      MBL-C, was present on day 4.5 pc especially after mating with DBA/2 males. High
      levels of MBL are present in the uterine luminal fluid of sterile women, and
      possible functions for TWEAK and MBL in human implantation are indicated by their
      protein and mRNA expression in uterine biopsies from infertile and fertile
      individuals. Consistent with the results in mice, increased MBL expression is
      linked with pregnancy failure. Serum and uterine VEGF and VEGF receptor levels
      are also different between fertile and sterile patients. The implications of
      these findings for utilising the CBA/JxDBA/2 mating combination as an early onset
      model of preeclampsia are discussed.

PMID- 19854518
TI  - Gonadotropin-releasing hormone/human chorionic gonadotropin beta based
      recombinant antibodies and vaccines.
AB  - Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) are
      unique targets for the control of fertility. Immunological approaches to
      neutralizing these hormones have additional utility in cancer treatment. Vaccines
      have been developed against both GnRH and hCG and these have undergone Phase I/II
      clinical trials documenting their safety, reversibility and efficacy. The
      heterospecies dimer hCG vaccine prevented pregnancy in women of proven fertility
      without impairment of ovulation or derangement of menstrual regularity and
      bleeding profiles. The protective threshold of antibody titers to achieve
      efficacy was determined in these first-ever trials. Recently, a recombinant
      vaccine against the beta subunit of hCG linked to the B subunit of heat labile
      enterotoxin has been made and expressed as a glycosylated conjugate in Pichia
      pastoris. Experiments indicate its ability to generate antibodies above the
      protective threshold in all immunized Balb/c mice. Ectopic expression of
      hCG/hCGbeta is observed in many advanced stage cancers of various origins. A
      chimeric high affinity and specific recombinant antibody against hCGbeta linked
      to curcumin kills hCGbeta expressing T lymphoblastic leukemia cells without any
      deleterious effect. Several synthetic and recombinant vaccines have been
      developed against GnRH. These reduce serum testosterone to castration levels
      causing atrophy of the prostate. Three Phase I/II clinical trials conducted in
      India and Austria have shown that these vaccines elicit non-surgical reduction of
      testosterone, a fall in prostate specific antigen and clinical improvement of
      prostate carcinoma patients. A multimer recombinant vaccine against GnRH has high
      efficacy for sterilization of pigs and other animals.

PMID- 19854519
TI  - Cognitive and electroencephalographic disturbances in children with attention
      deficit/hyperactivity disorder and sleep problems: new insights.
AB  - There is overlap between the behavioural symptoms and disturbances associated
      with Attention-Deficit/Hyperactivity Disorder (AD/HD) and sleep problems. The aim
      of this study was to examine the extent of overlap in cognitive and
      electrophysiological disturbances identified in children experiencing sleep
      problems and children with AD/HD or both. Four groups (aged 7-18) were compared:
      children with combined AD/HD and sleep problems (n=32), children with AD/HD
      (n=52) or sleep problems (n=36) only, and children with neither disorder (n=119).
      Electrophysiological and cognitive function measures included: absolute EEG power
      during eyes open and eyes closed, event-related potential (ERP) components
      indexing attention and working memory processes (P3), and a number of standard
      neuropsychological tests. Children with symptoms of both AD/HD and sleep problems
      had a different profile from those of children with either AD/HD or sleep
      problems only. These findings suggest it is unlikely that disturbances in brain
      and cognitive functioning associated with sleep problems also give rise to AD/HD
      symptomatology and consequent diagnosis. Furthermore, findings suggest that
      children with symptoms of both AD/HD and sleep problems may have a different
      underlying aetiology than children with AD/HD-only or sleep problems-only,
      perhaps requiring unique treatment interventions.

PMID- 19854520
TI  - Porcine allergy and IgE.
AB  - Anaphylaxis was reported in 1963 in pigs experimentally sensitized with ovalbumin
      and was subsequently associated indirectly with IgE-related antibodies by
      functional assays to confirm heat-labile passive cutaneous anaphylaxis (PCA),
      reverse passive anaphylaxis (RPA) and Prausnitz-Kustner (PK) reactions to this
      and other allergens. The immunoglobulin mediating immediate hypersensitivity
      could be cross-adsorbed with anti-human IgE. Porcine IgE epsilon chain has been
      cloned and sequenced. Rabbit anti-pig IgE has been described by two groups, as
      has cross reactivity with pig IgE of various heterologous polyclonal and
      monoclonal anti-IgEs. Pigs develop transient post-weaning food allergy to soy
      allergens which can be prevented by pre-weaning feeding of soy proteins in
      sufficient quantity. Natural hypersensitivity also occurs to nematodes. Recently,
      experimental allergy has been induced in outbred pigs to peanut and to egg
      allergens which manifest as respiratory, cutaneous and enteric signs similar to
      those of human food allergy. These models are platforms for comparative allergy
      research as realistic alternatives to use of inbred mice or humans for
      investigation of pathogenesis, prophylaxis and therapy.

PMID- 19854521
TI  - Evaluation of the upper airway in children and adolescents with cystic fibrosis
      and obstructive sleep apnea syndrome.
AB  - OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) in cystic fibrosis (CF)
      patients may be associated with the presence of upper airway obstruction caused
      by chronic infection and nasal polyposis that may also contribute to OSAS
      severity. Our objective was to identify the profile of findings in CF and OSAS
      patients by performing upper airway examinations. METHODOLOGY: Observational,
      cross-sectional study involving 63 children and adolescents between the ages of 2
      and 14 with CF. All patients answered a questionnaire and underwent a standard
      otolaryngology examination, including an endoscopic nasal and nocturnal
      polysomnography. OSAS diagnosis was confirmed if the obstructive apnea index was
      >or=1. RESULTS: OSAS was identified in 35 (55.6%) patients. The upper airway
      findings were evaluated using multiple correspondence factorial analysis. The
      OSAS group presented with overjet >2mm, enlarged pharyngeal pillars, palatine
      tonsils and pharyngeal tonsils hypertrophy, ogival hard palates and
      characteristics of chronic rhinosinusitis. CONCLUSION: Bone and soft tissue
      structural alterations of the upper airway and chronic rhinosinusitis were
      associated with the OSAS group patients.

PMID- 19854522
TI  - Suspended C60 nanoparticles protect against short-term UV and fluoranthene photo
      induced toxicity, but cause long-term cellular damage in Daphnia magna.
AB  - The increased production of nanotechnology materials is a potential source of
      nano-sized particles (NSPs) in aquatic ecosystems. Meanwhile, polycyclic aromatic
      hydrocarbons (PAHs), in the presence of ecologically relevant levels of
      ultraviolet radiation (UV), can be acutely toxic to aquatic species including
      fish and invertebrates. Considering that suspended carbon-based NSPs (e.g., C60
      fullerenes) may act in similar ways as dissolved organic matter (DOM) by altering
      the bioavailability of PAHs, the objective of this research was to determine the
      effect of suspended C60 on the photo-induced toxicity of fluoranthene.
      Transmission electron microscopy indicated that the presence of C60 protected
      cellular components (e.g., mitochondria, microvilli, and basal infoldings) in
      organisms exposed to UV and fluoranthene phototoxicity in short-term exposures.
      However, we found that long-term exposure (21d) of low-level C60 caused
      significant cellular damage in the Daphnia magna alimentary canal. This paper
      highlights the importance of examining the interactions between existing
      stressors and nanoparticles in the aquatic environment.

PMID- 19854523
TI  - Impact of home-based, supervised exercise on congestive heart failure.
AB  - AIMS: Comparison of supervised home-based exercise program as adjunctive therapy,
      with comprehensive disease management alone, on symptoms and quality of life in
      congestive heart failure patients. METHODS: 8 women and 11 men were enrolled in a
      randomized trial. The mean subject age was 69 (+/-4.44) in the controls and 70
      (+/-4.05) in the intervention group. Baseline and 3, 6, and 12-month evaluations
      consisted of the Chronic Heart Failure Questionnaire (CHFQ), measuring perceived
      functional capacity (perceived symptoms of dyspnea, fatigue, and emotional
      function) and the Yale Physical Activity Survey (YPAS). A stress test was given
      at baseline and 12 months. RESULTS AND CONCLUSIONS: The home-based exercise
      intervention caused a significant change in perceived fatigue between study
      groups (p=0.015), after 6 months of study participation, with the control group
      feeling less fatigued than the intervention group. After 12 months of
      participation, there were no significant differences in perceived functional
      capacity. Home-based exercise was well tolerated and favorably evaluated. This
      pilot study demonstrates the feasibility of studying home-based exercise in
      patients with moderate congestive heart failure. Larger and longer studies will
      be required to determine treatment effects.

PMID- 19854524
TI  - Justification for inter-fraction correction of catheter movement in fractionated
      high dose-rate brachytherapy treatment of prostate cancer.
AB  - BACKGROUND AND PURPOSE: Fractionated high dose-rate (HDR) brachytherapy in the
      treatment of prostate cancer relies on reproducible catheter positions for each
      fraction to ensure adequate tumour coverage while minimising dose to normal
      tissues. Peri-prostatic oedema may cause caudal displacement of the catheters
      relative to the prostate gland between fractions. This can be corrected for by
      changing source dwell positions or by physical re-advancement of catheters before
      treatment. MATERIALS AND METHODS: Data for 20 consecutive monotherapy patients
      receiving three HDR fractions of 10.5 Gy per fraction over 2 days were analysed
      retrospectively. Pre-treatment CT scans were used to assess the effect of
      catheter movement between fractions on implant quality, with and without movement
      correction. Implant quality was evaluated using dosimetric parameters. RESULTS:
      Compared to the first fraction (f1) the mean inter-fraction caudal movement
      relative to the prostate base was 7.9 mm (f2) (range 0-21 mm) and 3.9 mm (f3)
      (range 0-25.5 mm). PTV D90% was reduced without movement correction by a mean of
      27.8% (f2) and 32.3% (f3), compared with 5.3% and 5.1%, respectively, with
      catheter movement correction. Dose to 2 cc of the rectum increased by a mean of
      0.69 (f2) and 0.76 Gy (f3) compared with an increase of 0.03 and 0.04 Gy,
      respectively, with correction. The urethra V12 also increased by a mean of 0.36
      (f2) and 0.39 Gy (f3) compared with 0.06 and 0.16 Gy, respectively, with
      correction. CONCLUSIONS: Inter-fraction correction for catheter movement using
      pre-treatment imaging is critical to maintain the quality of an implant. Without
      movement correction there is significant risk of tumour under-dosage and normal
      tissue over-dosage. The findings of this study justify additional imaging between
      fractions in order to carry out correction.

PMID- 19854525
TI  - HDR endobronchial brachytherapy (HDRBT) in the management of advanced lung cancer
      -comparison of two different dose schedules.
AB  - PURPOSE: The aim of this work is to compare the results of various treatment
      protocols used in palliative HDRBT with the view of analyzing differences in
      survival and diminishing breathing difficulties. MATERIAL AND METHODS: A total of
      648 patients with advanced lung cancer were divided into two groups according to
      their clinical stage and the Zubrod-ECOG-WHO score. 303 (46.8%) patients received
      a total dose of 22.5 Gy in 3 fractions once a week, and 345 (53.2%) patients
      received a single fraction of 10 Gy. They were under clinical and endobronchial
      observation taking into consideration survival rates, local remission and
      duration of symptom relief such as dyspnoea, breathing, cough and haemoptysis.
      RESULTS: There was no difference in the length of survival time between the two
      groups of patients (log-rank test, p=0.055). Patients showing improvement
      (objective response) survived longer than those who showed no change or
      progression (F Cox, p=0.000001). In multivariate analysis the other statistically
      important prognostic factors were: clinical stage of primary tumor (F Cox,
      p=0.000002), Zubrod-ECOG-WHO score (F Cox, p=0.002) and age of patients (F Cox,
      p=0.004). CONCLUSIONS: The two treatment protocols showed similar efficiency in
      overcoming difficulties in breathing. Prognostic factors that significantly
      correlated with survival length were: grade of remission after treatment,
      clinical stage and performance status.

PMID- 19854526
TI  - Feasibility of the use of the Active Breathing Co ordinator (ABC) in patients
      receiving radical radiotherapy for non-small cell lung cancer (NSCLC).
AB  - INTRODUCTION: One method to overcome the problem of lung tumour movement in
      patients treated with radiotherapy is to restrict tumour motion with an active
      breathing control (ABC) device. This study evaluated the feasibility of using ABC
      in patients receiving radical radiotherapy for non-small cell lung cancer.
      METHODS: Eighteen patients, median (range) age of 66 (44-82) years, consented to
      the study. A training session was conducted to establish the patient's breath
      hold level and breath hold time. Three planning scans were acquired using the ABC
      device. Reproducibility of breath hold was assessed by comparing lung volumes
      measured from the planning scans and the volume recorded by ABC. Patients were
      treated with a 3-field coplanar beam arrangement and treatment time (patient on
      and off the bed) and number of breath holds recorded. The tolerability of the
      device was assessed by weekly questionnaire. Quality assurance was performed on
      the two ABC devices used. RESULTS: 17/18 patients completed 32 fractions of
      radiotherapy using ABC. All patients tolerated a maximum breath hold time >15s.
      The mean (SD) patient training time was 13.8 (4.8)min and no patient found the
      ABC very uncomfortable. Six to thirteen breath holds of 10-14 s were required per
      session. The mean treatment time was 15.8 min (5.8 min). The breath hold volumes
      were reproducible during treatment and also between the two ABC devices.
      CONCLUSION: The use of ABC in patients receiving radical radiotherapy for NSCLC
      is feasible. It was not possible to predict a patient's ability to hold breath. A
      minimum tolerated breath hold time of 15 s is recommended prior to commencing
      treatment.

PMID- 19854527
TI  - Problems of diabetes management in the immigrant population in Germany.
AB  - AIM: To compare prospectively the effect of diabetes management in the immigrant
      and the native population in Berlin, Germany. METHODS: Diabetes patients
      attending a metabolic outpatient clinic in an area with a high immigrant
      population were studied at the start of the training program and after 12 months
      of participation. RESULTS: 1607 of 2099 patients with at least one post-training
      visit (76.6%) provided analysable data. Of these 362 (22.5%) were immigrants.
      Initial hemoglobin A1c (HbA1c) was higher in the immigrants. Immigrants were 5
      years younger and had a more recent diagnosis of diabetes. HbA1c fell by 1.4 and
      1.5 percentage points in the immigrants and natives, leaving a greater proportion
      of the immigrants above the target value of 6.5%. Analysis of patients matched
      according to baseline HbA1c, sex and age showed a smaller decrease in mean
      HbA(1c) for the immigrants. The percent of patients with hypertension, obesity,
      dyslipidaemia or diabetic complications was comparable in both groups initially
      and after 12 months. CONCLUSION: Immigrants had a higher HbA1c concentration at
      baseline and after 12 months compared to natives, despite a similar decline in
      HbA1c percentage points. More investigations are warranted to identify the
      causes, such as dietary habits, language difficulties, education and others.

PMID- 19854528
TI  - Europe's hepatitis challenge: defusing the "viral time bomb".
AB  - Since its foundation in 2005, the European Liver Patients' Association (ELPA) - a
      not-for-profit-organisation with 21 members across Europe - has been at the
      forefront of raising awareness of liver diseases, in particular hepatitis,
      throughout the EU. In line with the main challenge for hepatitis carriers, which
      is to "become a patient", ELPA calls for targeted screening of risk groups in
      order to facilitate early diagnosis and, if appropriate, treatment. To this end,
      ELPA and its members have embarked on a multi-level lobbying campaign, involving
      EU and national policymakers, liver specialist associations and public health
      experts. First successes include the adoption of the European Parliament's
      Written Declaration on Hepatitis C and the European Centre for Disease Prevention
      and Control's (ECDC) decision to include viral hepatitis in its annual work plan
      as of 2008, as well as a compilation of expert recommendations on screening,
      which were endorsed by the European Association for the Study of the Liver
      (EASL). For a sustainable change in the perception of liver diseases by the
      public and decision-makers in public health and a subsequent improvement of the
      situation for patients and specialists, it will be important for both to move
      beyond the immediate doctor-patient relationship and address jointly a wider
      audience. Essential in this context is the link to cancer. Policymakers have to
      know that by taking preventative measures (primary and secondary) against liver
      disease they prevent liver cancer, one of the few cancers on the rise in Europe.

PMID- 19854529
TI  - Factors associated with differences in mortality and self-reported health across
      states in the United States.
AB  - OBJECTIVE: Recent studies indicate continuing health disparities across
      geographic units in the US. This paper provides updated estimates of the
      association between socioeconomic factors and population health using a new state
      level dataset and panel econometric methods that account for state-specific
      effects and autoregressive error structure. METHODS: Data from multiple sources
      for the 50 US states and the District of Columbia are merged. The dependent
      variables are age-adjusted all-cause mortality, self-assessed health status, and
      number of healthy days. Panel econometric models are used to accommodate state
      specific unobserved factors and to incorporate autoregressive random disturbances
      to provide consistent and robust estimates. RESULTS: A 1-unit increase in the
      number of physicians per 1000 population is associated with a reduction in
      mortality by 30/100,000. The effects of physician-to-population ratio on self
      reported health measures are mixed. Socioeconomic, demographic, as well as the
      prevalence of smoking and obesity have varying effects on mortality and self
      reported measures of health. CONCLUSIONS: The new estimate of the association
      between physician supply and lower mortality suggests continuing efforts to
      assess the need for policies and incentives to induce physician labor supply in
      underserved states. Strategies and policies to reduce health disparities should
      address social, economic and individual risk factors.

PMID- 19854530
TI  - The moment segmentation analysis of heart sound pattern.
AB  - This paper presents two new ideas. The first one is to apply the Viola integral
      waveform method to analyze the heart sounds recorded by an electric stethoscope,
      and the multi-scale moment analysis is proposed to locate each cycle of heart
      sounds. A fast algorithm for calculating characteristic waveform (CW) and
      characteristic moment waveform (CMW) of heart sound can be expressed by the Viola
      integral method, and their calculation time has nothing to do with their scales.
      The second idea is easier to segment the heart sound based on its approximate
      cyclical characteristic than the ordinary methods. Each heart sound cycle can be
      quickly found by CMW's Local Extreme Points (LEPs). Based on the information of
      LEPs and CW, a high accurate search algorithm to segment S1 and S2 sounds is
      submitted. By numerical experiments, the important parameters of time scale
      delta=0.05s for CW and l=0.45s for CMW are obtained and validated for
      segmentation of heart sound. CONCLUSION: More exact segmentation boundaries of
      the heart sound signal could be located fast in an automated way, and a further
      performance analysis is presented. Owing to the use of the rhythm of CMW curves,
      the proposed method not only gives a higher success segmentation rate, but also
      it is actually simpler and faster than the wavelet method.

PMID- 19854531
TI  - Cell accelerated cryoablation simulation.
AB  - Tumor cryoablation is a clinical procedure where supercooled probes are used to
      destroy cancerous lesions. Cryoablation is a safe and effective palliative
      treatment for skeletal metastases, providing immediate and long term pain relief,
      increasing mobility and improving quality of life. Ideally, lesions are
      encompassed by an ice ball and frozen to a sufficiently low temperature to ensure
      cell death. "Lethal ice" is the term used to describe regions within the ice ball
      where cell death occurs. Failure to achieve lethal ice in all portions of a
      lesion may explain the high recurrence rate currently observed. Tracking growth
      of lethal ice is critical to success of percutaneous ablations, however, no
      practical methods currently exist for non-invasive temperature monitoring.
      Physicians lack planning tools which provide accurate estimation of the ice
      formation. Simulation of ice formation, while possible, is computationally
      demanding and too time consuming to be of clinical utility. We developed the
      computational framework for the simulation, acceleration strategies for multicore
      Intel x86 and IBM Cell architectures, and performed preliminary validation of the
      simulation. Our results demonstrate that the streaming SIMD implementation has
      better performance and scalability. Both accelerated and non-accelerated
      algorithms demonstrate good agreement between simulation and manually identified
      ice ball boundaries in phantom and patient images. Our results show promise for
      the development of novel cryoablation planning tools with real-time monitoring
      capability for clinical use.

PMID- 19854532
TI  - Interactive computer-based simulator for training in blade navigation and
      targeting in myringotomy.
AB  - A virtual-reality simulator was developed for the training of Otolaryngology (Ear
      Nose-Throat) surgical residents to perform myringotomy, a relatively common
      surgical procedure in which an incision is made in the eardrum mainly to treat
      middle-ear infections. The simulator presents the trainee with a three
      dimensional (3D) virtual model of the ear that can be viewed through a mock
      surgical microscope consisting of a stereo visor mounted on a custom-designed
      stand. The trainee interacts with the virtual ear using a real myringotomy blade,
      the movements of which are tracked in real time using a stereo optical tracker.
      Interactions of the blade with virtual tissues are calculated and rendered on the
      visor using freely available physics and graphics software engines. Six
      experienced surgical residents and surgeons assessed the effectiveness of the
      simulator as a viable training tool by completing a questionnaire designed
      specifically for this study after using the simulator. Surgeons and residents
      were positively impressed by the simulator as a training tool and would recommend
      its use as part of training.

PMID- 19854533
TI  - Clinical outcome of patients with non-small cell lung cancer receiving front-line
      chemotherapy according to EGFR and K-RAS mutation status.
AB  - BACKGROUND: Somatic mutations in EGFR and K-RAS may predict for sensitivity and
      resistance to EGFR tyrosine kinase inhibitors (TKIs). Whether EGFR and K-RAS
      mutations could also predict clinical outcome of non-small cell lung cancer
      (NSCLC) patients following front-line chemotherapy has not yet been established.
      PATIENTS AND METHODS: One hundred and sixty-two chemotherapy-naive patients with
      locally advanced/metastatic NSCLC who received front-line chemotherapy were
      included in this retrospective study and their clinical outcome data was analyzed
      according to EGFR and K-RAS mutation status of their tumors. RESULTS: Classical
      activating EGFR and K-RAS mutations were found in 8.2 and 22.6% of patients
      respectively and were not associated with patients' clinicopathological
      characteristics. Patients with classical EGFR mutations had a higher probability
      of response to front-line chemotherapy as compared to those with wild type EGFR
      (p=0.023). Multivariate analysis showed that the presence of activating EGFR
      mutations was an independent factor associated with response to front-line
      chemotherapy (HR=4.85; 95% CI: 1.13-20.83, p=0.034). K-RAS mutation status was
      not associated with response to front-line chemotherapy. The presence of
      activating EGFR but not of K-RAS mutations was associated with a significantly
      higher overall survival compared to patients without mutations treated with
      platinum-based front-line chemotherapy (p=0.043). CONCLUSIONS: The data indicate
      that EGFR mutation status could be predictive for response to cytotoxic front
      line chemotherapy in patients with NSCLC. Additional prospective studies are
      needed in order to validate this observation and to define whether these patients
      should be preferentially treated with front-line TKIs or chemotherapy.

PMID- 19854534
TI  - KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer.
AB  - The let-7 family of microRNAs are important regulatory molecules in lung cancer.
      One downstream target of let-7 is the RAS gene family, including KRAS, an
      important oncogene in the etiology and clinical outcome of lung adenocarcinoma.
      Recently, a SNP in the let-7 binding region of the KRAS 3' UTR was identified
      (termed LCS6). This functional polymorphism alters let-7 binding, resulting in
      both increased KRAS expression and decreased let-7 exposure. Further, this SNP
      has been reported as a risk trait for lung cancer among low-moderate smokers.
      Given the functionality of LCS6, we tested the hypothesis that this SNP is
      associated with the occurrence of KRAS mutation as well as patient survival.
      Here, we report there is no association between the LCS6 KRAS polymorphism and
      KRAS mutation. Further, we find no association between the LCS6 polymorphism and
      lung cancer survival. These unexpected findings imply that this newly reported
      KRAS-LCS6 polymorphism will have limited clinical utility for NSCLC.

PMID- 19854535
TI  - Alternating 2'-O-ribose methylation is a universal approach for generating non
      stimulatory siRNA by acting as TLR7 antagonist.
AB  - Small interfering RNA (siRNA) is widely used to modulate gene expression, but its
      potential induction of cytokines via Toll-like receptors (TLR) strongly impairs
      its use. Selective 2'-O-ribose methylation of sense or antisense strand can
      abolish the immunostimulatory potential, however, no universal approach is
      available and the mechanism of action is unknown. Here, we demonstrate that
      alternating 2'-O-ribose methylation of the sense strand within a siRNA duplex
      specific for eGFP or beta(2)-microglobulin destroyed its immunostimulatory
      function in primary immune cells, while reduction in target gene expression was
      functional. Furthermore, addition of siRNA containing a 2'-O-ribose-methylated
      sense strand to immunostimulatory siRNA abolished its stimulatory activity and
      binding studies revealed that 2'-O-ribose-methylated RNA bound stronger to TLR7
      than unmodified RNA. We conclude that 2'-O-ribose methylation acts as inhibitor
      for RNA-driven immune stimulation via TLR7 and recommend alternating 2'-O-ribose
      methylation of the sense strand as a universal approach for the generation of non
      immunostimulatory siRNA.

PMID- 19854536
TI  - Changes in iron and organic acid concentrations in xylem sap and apoplastic fluid
      of iron-deficient Beta vulgaris plants in response to iron resupply.
AB  - In this study, the effects of Fe resupply on the composition of the xylem sap and
      apoplastic fluid of Fe-deficient sugar beet plants were investigated. Experiments
      were carried out in growth chambers with plants grown in hydroponics, and Fe
      resupply to Fe-deficient plants was carried out by adding 45muM Fe(III)-EDTA to
      the nutrient solution. In the short term (within 24h), Fe resupply caused marked
      changes in the xylem sap and apoplastic fluid composition and in leaf
      physiological parameters when de novo chlorophyll (Chl) synthesis was still
      beginning. Major changes included: (i) 10- and 5-fold increases in Fe
      concentrations in apoplastic fluid and xylem sap, respectively; (ii) marked
      decreases in the concentrations of organic acids in apoplastic fluid, but not in
      xylem sap and (iii) large decreases in the citrate/Fe ratios, both in apoplastic
      fluid and in xylem sap. Two to four days after Fe resupply, xylem sap and
      apoplastic fluid Fe and organic acid concentrations and pH reached values similar
      to those obtained in Fe-sufficient leaves. Leaf mesophyll ferric chelate
      reductase (FC-R) activities and photosynthetic rates increased gradually during
      recovery from Fe deficiency.

PMID- 19854537
TI  - [Early visual screening appears essential to detect complete amblyopia risk and
      to treat strabismus earlier].
AB  - INTRODUCTION: Early medical examinations performed in 2-, 4-, 9-, and 24-month
      olds need to set up a technique adapted to infants and children. The aim of this
      study was to describe the technique and the results of screening performed by
      physicians of the Hauts-de-Seine district in 2004. PATIENTS AND METHODS: Over 1
      year, 17 participating centers of the Maternal and Infant Welfare department of
      the Hauts-de-Seine district (France) included 1366 children at the 9- and 24
      month medical consultation. This standardized procedure looked for personal and
      family risk factors and sought to detect ocular anomalies, strabismus, and
      amblyopia. Depending on the results, the patient was oriented toward appropriate
      care. RESULTS: At inclusion, only 10% of the children had already consulted an
      ophthalmologist with insufficient numbers in the risk groups although the
      difference between groups was significant. Of the children included, 30.2% had a
      family history of visual impairment and 7% a personal risk. During the
      examination, a risk of visual impairment was suspected for 12.5% of the children.
      At the end of the consultation, 39.7% of the children were oriented to an
      ophthalmic consultation, with the history or the results of the examination. One
      of these children out of two underwent a consultation. Finally, 31 children were
      prescribed corrective glasses compared to only eight wearing glasses initially
      and 65 children were followed up as opposed to only seven children before the
      study. CONCLUSION: This screening has led to quadrupling the number of children
      wearing corrective lenses and monitoring the others presenting visual
      abnormalities, confirming the advantages of early visual screening for children
      under 3 years of age.

PMID- 19854538
TI  - Focusing on patients at high-risk for glaucoma in Brazil: a pilot study.
AB  - PURPOSE: To assess the results of a pilot study for screening high-risk
      individuals for glaucoma in Brazil. METHODS: Using cross-sectional methodology,
      the study population consisted of first-degree relatives of known glaucoma
      patients. Risk factors were assessed through a questionnaire, and each subject
      received a complete eye examination. RESULTS: Sixty individuals were identified
      and examined. The most relevant risk factors for glaucoma were: age older than 40
      years (86.7%), systemic hypertension (46.7%), and self-identification as non
      white (35%). Final diagnoses were normal (63.3%), glaucoma (23.3%), ocular
      hypertension (11.7%), and angle-closure without glaucoma (1.7%). Clinical
      features that were significant as an indicator of glaucoma presence were non
      white participants (OR=6.7, p=0.004), central corneal thickness < 520 microm
      (OR=6.286, p=0.007), and cup-to-disc ratio >or= 0.6 (OR=3.00, p=0.07).
      CONCLUSIONS: Despite our study's small sample size, this high prevalence of
      glaucoma (23.3%) highlights the importance of identifying for screening at-risk,
      first-degree relatives of glaucoma patients. Pachymetry was an important
      diagnostic tool for glaucoma within this population.

PMID- 19854539
TI  - [Evaluation of NAAGA efficacy in dry eye syndrome].
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of Naabak((R))
      eyedrops in reducing inflammation in dry eye syndrome. PATIENTS AND METHODS: This
      pilot, multicenter, randomized, double-blind, parallel study was carried out in
      adult patients suffering from moderate dry eye syndrome. Patients were treated
      for three months with preservative-free NAAGA (Naabak((R))) or with sodium
      chloride 0.9% without preservative (Larmabak(R)). They received the treatment
      four to six times a day during the 1(st) month and three to four times a day
      during the 2(nd) and 3(rd) months. At each visit (D28 and D84), clinical tests
      were performed as well as a biological evaluation of HLA-DR and MUC5AC expression
      on conjunctival imprints using flow cytometry. RESULTS: After three months of
      treatment, the ocular surface symptoms and overall discomfort were improved in
      patients treated with Naabak(R) and in those treated with Larmabak(R) with no
      significant difference between the groups. Cytological impression showed a
      significant decrease in the expression of inflammatory markers, notably antigen
      HLA-DR, in the Naabak(R) group. CONCLUSION: This study confirms the anti
      inflammatory property of preservative-free NAAGA (Naabak(R)) in the context of
      dry eye syndrome with a similar clinical efficacy compared to sodium chloride
      solution (Larmabak(R)). Naabak(R) could present an additional advantage compared
      to artificial tears and could be indicated in the treatment of moderate
      inflammatory dry eye syndrome.

PMID- 19854540
TI  - [Spontaneous subretinal isolated hematomas or associated with macular
      degeneration: a retrospective review of 95 cases].
AB  - INTRODUCTION: Diagnosis of choroidal hematoma, either spontaneous or associated
      with age-related macular degeneration, is clinical. In some cases of expansive or
      posterior lesion, hematoma may be misdiagnosed as a tumor. MRI and color Doppler
      imaging (CDI) are important in ruling out uveal melanoma in these cases. PATIENTS
      AND METHODS: We reviewed the clinical, MRI, and ultrasonographic characteristics
      of 95 patients sent to the Curie Institute for suspected uveal melanoma between
      1998 and 2006, whose final diagnosis was a choroidal hematoma. Imaging
      differences with melanomas are discussed. RESULTS: A total of 95 patients with a
      diagnosis of hematoma were seen; the age varied from 54 to 92 years with a median
      age of 77 years; there was a history of macular degeneration in 27 cases and 11
      patients were taking an anticoagulant. Intravitreous hemorrhage was noted in 18
      cases and the lesion was located in the posterior pole in 28 cases. The thickness
      of the lesions measured by B scan ultrasonography varied between 1 and 7.8mm,
      with a mean thickness of 2.86mm. MRI was performed in 27 cases and CDI in ten
      cases. On CDI, hematomas appeared as linear or regular bulging lesions with no
      intralesional blood flow. On MRI, hematomas appeared as a high-intensity signal
      on T1-weighted images, heterogeneous on T2-weigted images in relation to the
      progression of the clot, but no contrast enhancement was noted inside the lesion.
      Follow-up examinations showed the progressive involvement of the clot and delayed
      decreasing size of the lesion. CONCLUSION: The diagnosis of choroidal hematoma is
      usually made by fundus examination. In some posterior locations with pseudo
      tumoral appearance, CDI and MRI are useful to rule out a uveal tumor.

PMID- 19854541
TI  - Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of
      mortality in patients with sepsis.
AB  - STUDY OBJECTIVE: Abnormal (both low and high) central venous saturation (ScvO(2))
      is associated with increased mortality in emergency department (ED) patients with
      suspected sepsis. METHODS: This was a secondary analysis of 4 prospectively
      collected registries of ED patients treated with early goal-directed therapy
      based sepsis resuscitation protocols from 4 urban tertiary care hospitals.
      Inclusion criteria were sepsis, hypoperfusion defined by systolic blood pressure
      less than 90 mm Hg or lactate level greater than or equal to 4 mmol/L, and early
      goal-directed therapy treatment. ScvO(2) levels were stratified into 3 groups:
      hypoxia (ScvO(2) <70%); normoxia (ScvO(2) 71% to 89%); and hyperoxia (ScvO(2) 90%
      to 100%). The primary exposures were initial ScvO(2) and maximum ScvO(2)
      achieved, with the primary outcome as inhospital mortality. Multivariate analysis
      was performed. RESULTS: There were 619 patients who met criteria and were
      included. For the maximum ScvO(2), compared with the mortality rate in the
      normoxia group of 96 of 465 (21%; 95% confidence interval [CI] 17% to 25%), both
      the hypoxia mortality rate, 25 of 62 (40%; 95% CI 29% to 53%) and hyperoxia
      mortality rate, 31 of 92 (34%; 95% CI 25% to 44%) were significantly higher,
      which remained significant in a multivariate modeling. When the initial ScvO(2)
      measurement was analyzed in a multivariate model, only hyperoxia was
      significantly higher. CONCLUSION: The maximum ScvO(2) value achieved in the ED
      (both abnormally low and high) was associated with increased mortality. In
      multivariate analysis for initial ScvO(2), the hyperoxia group was associated
      with increased mortality, but not the hypoxia group. This study suggests that
      future research aimed at targeting methods to normalize high ScvO(2) values by
      therapies that improve microcirculatory flow or mitochondrial dysfunction may be
      warranted.

PMID- 19854543
TI  - [Pneumonia and the acute respiratory distress syndrome due to influenza A (H1N1)
      virus].
AB  - The acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are
      part of a devastating syndrome characterized by acute onset, hypoxemia, and
      bilateral infiltrates on chest x-rays. ALI/ARDS is the response of the lung to a
      local or systemic aggression, resulting in local inflammation and coagulation
      disorders, which lead to increased inflammatory pulmonary edema. ARDS is a major
      cause of morbidity, death, and cost in intensive care units. The most common
      cause is sepsis. We present a case of ARDS secondary to infection with the
      influenza A (H1N1) virus. The influenza A (H1N1) virus caused a global pandemia
      91 years ago, with sporadic outbreaks afterward. The new influenza A pandemia was
      transmitted from swine to humans. Infection by the influenza A (H1N1) virus can
      cause severe respiratory illness, the acute respiratory distress syndrome, and
      secondary infections among healthcare workers.

PMID- 19854544
TI  - [Risk factors for falls amongst older people living in nursing home. A cohort
      study].
AB  - OBJECTIVE: To determine factors associated with falls in institutionalized
      elderly. MATERIAL AND METHODS: A prospective cohort study was carried out, over a
      18 months period. We included 203 subjects aged 65 and over who were able to
      walk. We recorded: age, sex, BMI, Barthel, Pfeiffer, Tinetti and FRAT tests,
      history of falls during the previous year, walking aids, the existence of
      orthostatic hypotension, delirium in the previous month, presence of various
      chronic diseases (10), number and nature of the usual drugs (15). Each fall was
      recorded by the nurse in charge of the patient. The analysis was carried out
      using logistic regression. RESULTS: The average age of participants was 80.1
      (SD=9.1) years, male 37.9%. There were 35 losses (11.5%/year). 204 falls were
      registered in 99 people (48.8% cumulative incidence at 18 months of follow-up).
      44 people (21.7%) suffered repeated falls. Regression analysis showed association
      with the presence of delirium in the month prior to the inclusion in the study
      (OR 6.7; CI95% 1.6-30.3) and a smaller BMI (OR 1.1; CI95% 1.01-1.12), and visual
      impairment in the case of repeated falls (OR 2.2; CI95% 1.1-4.5). CONCLUSION: The
      incidence of falls in institutionalized elderly is high. It was found strong
      association with some conditions of fragility as indicators of risk.

PMID- 19854545
TI  - Synthesis, structure, electrochemistry and spectral characterization of (D
      glucopyranose)-4-phenylthiosemicarbazide metal complexes and their antitumor
      activity against Ehrlich ascites carcinoma in Swiss albino mice.
AB  - The novel glycosyl saccharide derivative, (D-glucopyranose)-4
      phenylthiosemicarbazide (LH) and its complexes, with cobalt(II), nickel(II),
      copper(II) and zinc(II) were synthesized, characterised and tested for cytotoxic
      effects. The copper complex, [CuLCl] inhibited Ehrlich Ascites Carcinoma (EAC)
      induced cancer cell lines in Swiss albino mice at LC50=1.94 x 10(-8) (LC50=2.76 x
      10(-8) for cisplatin) and so distinctly better than free ligand and other
      complexes.

PMID- 19854546
TI  - [Neurological involvement in Behcet disease].

PMID- 19854547
TI  - Dissipation of polycyclic aromatic hydrocarbons (PAHs) in the rhizosphere:
      synthesis through meta-analysis.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widespread and persistent organic
      pollutants with high carcinogenic effect and toxicity; their behavior and fate in
      the soil-plant system have been widely investigated. In the present paper, meta
      analysis was used to explore the interaction between plant growth and dissipation
      of PAHs in soil based on the large body of published literature. Plants have a
      promoting effect on PAH dissipation in soils. There was no difference in PAH
      dissipation between soils contaminated with single and mixed PAHs. However,
      plants had a more obvious effect on PAH dissipation in freshly-spiked soils than
      in long-term field-polluted soils. Additionally, a positive effect of the number
      of microbial populations capable of degrading PAHs was observed in the
      rhizosphere compared with the bulk soil. Our meta-analysis established the
      importance of the rhizosphere effect on PAH dissipation in variety of the soil
      plant systems.

PMID- 19854548
TI  - Elevated CO2 response of photosynthesis depends on ozone concentration in aspen.
AB  - The effect of elevated CO(2) and O(3) on apparent quantum yield (varphi), maximum
      photosynthesis (P(max)), carboxylation efficiency (V(cmax)) and electron
      transport capacity (J(max)) at different canopy locations was studied in two
      aspen (Populus tremuloides) clones of contrasting O(3) tolerance. Local light
      climate at every leaf was characterized as fraction of above-canopy
      photosynthetic photon flux density (%PPFD). Elevated CO(2) alone did not affect
      varphi or P(max), and increased J(max) in the O(3)-sensitive, but not in the O(3)
      tolerant clone. Elevated O(3) decreased leaf chlorophyll content and all
      photosynthetic parameters, particularly in the lower canopy, and the negative
      impact of O(3) increased through time. Significant interaction effect, whereby
      the negative impact of elevated O(3) was exaggerated by elevated CO(2) was seen
      in Chl, N and J(max), and occurred in both O(3)-tolerant and O(3)-sensitive
      clones. The clonal differences in the level of CO(2)xO(3) interaction suggest a
      relationship between photosynthetic acclimation and background O(3)
      concentration.

PMID- 19854549
TI  - Maintenance of kidney function following treatment with eculizumab and
      discontinuation of plasma exchange after a third kidney transplant for atypical
      hemolytic uremic syndrome associated with a CFH mutation.
AB  - Kidney transplant in patients with atypical hemolytic uremic syndrome (aHUS) is
      associated with a poor outcome because of recurrent disease, especially in
      patients known to have a factor H mutation. Long-term prophylactic plasma
      exchange and combined liver-kidney transplant have prevented graft loss caused by
      recurrence. However, the mortality associated with liver transplant is not
      negligible, and prophylactic plasma exchange requires permanent vascular access
      and regular hospitalization and exposes the patient to potential allergic
      reactions to plasma. Eculizumab is a high-affinity humanized monoclonal antibody
      that binds to C5 and thus prevents generation of C5a and the membrane attack
      complex. We report the case of a 17-year-old girl with aHUS associated with a
      mutation in the gene for complement factor H (CFH; c.3572C>T, Ser1191Leu) who was
      highly dependent on plasma exchange. Because of severe allergic reactions to
      plasma after the third renal graft, eculizumab was introduced in place of plasma
      exchange without problems. This and other reports suggest that the promise of
      complement inhibitors in the management of aHUS is going to be fulfilled.

PMID- 19854550
TI  - Is there a role for intradialytic parenteral nutrition? A review of the evidence.
AB  - Protein-energy wasting (PEW) is highly prevalent in people with stages 4 and 5
      chronic kidney disease, particularly in maintenance dialysis patients, and many
      indicators of PEW correlate strongly with mortality. Consequently, the causes,
      prevention, and treatment of PEW are active areas of investigation. A major cause
      of PEW is insufficient intake of nutrients, especially protein and energy
      (calories). Standard methods for increasing nutritional intake in patients with
      chronic kidney disease with PEW include dietary counseling and use of food
      supplements. If nutrient intake does not increase sufficiently, tube feeding and
      total parenteral nutrition may be considered. For maintenance hemodialysis
      patients, intradialytic parenteral nutrition (IDPN), an intravenous infusion of
      essential nutrients during hemodialysis treatments, may be used. Many studies
      have evaluated the effectiveness and safety of IDPN and show that IDPN has a good
      safety profile and also may improve protein-energy status. However, most studies
      have limitations in experimental design, such as small numbers of patients, lack
      of adequate controls, inclusion of patients without PEW, uncontrolled or
      unmonitored oral intake, nonrandomized design, or short duration. Additionally,
      most studies used nutritional or inflammatory indicators, rather than the more
      important outcomes of morbidity, mortality, or quality of life. Thus, although
      IDPN may partially satisfy the nutritional needs of maintenance hemodialysis
      patients who have or are at risk of PEW and who have substantial, but not
      adequate, protein and/or energy intake, longer term randomized prospective
      clinical trials with appropriate control groups are necessary to more
      definitively evaluate the clinical effectiveness and indications for IDPN.

PMID- 19854551
TI  - Studying large-scale programmes to improve patient safety in whole care systems:
      challenges for research.
AB  - Large-scale national and multi-institutional patient safety improvement
      programmes are being developed in the health care systems of several countries to
      address problems in the reliability of care delivered to patients. Drawing upon
      popular collaborative improvement models, these campaigns are ambitious in their
      aims to improve patient safety in macro-level systems such as whole health care
      organisations. This article considers the methodological issues involved in
      conducting research and evaluation of these programmes. Several specific research
      challenges are outlined, which result from the complexity of longitudinal, multi
      level intervention programmes and the variable, highly sociotechnical care
      systems, with which they interact. Organisational-level improvement programmes
      are often underspecified due to local variations in context and organisational
      readiness for improvement work. The result is variable implementation patterns
      and local adaptations. Programme effects span levels and other boundaries within
      a system, vary dynamically or are cumulative over time and are problematic to
      understand in terms of cause and effect, where concurrent external influences
      exist and the impact upon study endpoints may be mediated by a range of
      organisational and social factors. We outline the methodological approach to
      research in the United Kingdom Safer Patients Initiative, to exemplify how some
      of the challenges for research in this area can be met through a multi-method,
      longitudinal research design. Specifically, effective research designs must be
      sensitive to complex variation, through employing multiple qualitative and
      quantitative measures, collect data over time to understand change and utilise
      descriptive techniques to capture specific interactions between programme and
      context for implementation. When considering the long-term, sustained impact of
      an improvement programme, researchers must consider how to define and measure the
      capability for continuous safe and reliable care as a property of the whole care
      system. This requires a sociotechnical approach, rather than focusing upon one
      microsystem, disciplinary perspective or single level of the system.

PMID- 19854552
TI  - War exposure, daily stressors, and mental health in conflict and post-conflict
      settings: bridging the divide between trauma-focused and psychosocial frameworks.
AB  - This paper seeks to bridge the divisive split between advocates of trauma-focused
      and psychosocial approaches to understanding and addressing mental health needs
      in conflict and post-conflict settings by emphasizing the role that daily
      stressors play in mediating direct war exposure and mental health outcomes. The
      authors argue that trauma-focused advocates tend to overemphasize the impact of
      direct war exposure on mental health, and fail to consider the contribution of
      stressful social and material conditions (daily stressors). Drawing on the
      findings of recent studies that have examined the relationship of both war
      exposure and daily stressors to mental health status, a model is proposed in
      which daily stressors partially mediate the relationship of war exposure to
      mental health. Based on that model, and on the growing body of research that
      supports it, an integrative, sequenced approach to intervention is proposed in
      which daily stressors are first addressed, and specialized interventions are then
      provided for individuals whose distress does not abate with the repair of the
      social ecology.

PMID- 19854553
TI  - My face or yours? Event-related potential correlates of self-face processing.
AB  - The neural basis of self-recognition is mainly studied using brain-imaging
      techniques which reveal much about the localization of self-processing in the
      brain. There are comparatively few studies using EEG which allow us to study the
      time course of self-recognition. In this study, participants monitored a sequence
      of images, including 20 distinct images of their own face, a friend's face and a
      stranger's face articulating different speech sounds, while EEG was recorded from
      64 scalp electrodes. Differences in the ERP waveforms were observed very early
      on, with increased N170 and VPP amplitude to self relative to both friend and
      stranger measured over posterior and fronto-central sites, respectively. This
      'self effect' was also marked at approximately 250ms where P2/N2 amplitude was
      significantly reduced for self-faces. By comparison, differences between friend
      and stranger faces did not emerge until 250ms and beyond, where a more
      conventional 'familiarity effect' was observed. The data also point to a 'less
      lateralized' representation of self over posterior sites. These findings are
      consistent with both behavioral and fMRI studies which suggest that self-face
      processing is 'special' and are discussed with reference to EEG studies of face
      processing.

PMID- 19854554
TI  - Comparison of intravenous and intraosseous access by pre-hospital medical
      emergency personnel with and without CBRN protective equipment.
AB  - INTRODUCTION: Rapid intravascular access is a prerequisite component of emergency
      care and resuscitation. Peripheral intravenous (IV) access is the first-choice
      for most of the medical or trauma patients, but may be delayed in emergency
      conditions because of various difficulties. Elsewhere, intraosseous (IO) access
      may now be easily performed with a new semi-automatic battery-powered IO
      insertion device (EZ-IO. The aim of this study was to compare the overall time to
      establish IO infusion with the EZ-IO device and the equivalent time for
      peripheral IV infusion, performed by emergency personnel in standard (No-CBRN)
      and in chemical, biological, radiological, and nuclear (CBRN) protective
      equipment. METHODS: Nine nurses and 16 physicians randomly performed 4 procedures
      on a training manikin: IV and IO access under No-CBRN conditions and IV and IO
      under CBRN conditions. The time for each infusion attempt included all the steps
      essential for a simulated safe clinical use of infusion. RESULTS: Under No-CBRN
      conditions, the time to establish IO infusion was shorter than the equivalent IV
      time (50+/-9 vs 70+/-30s). Similarly, under CBRN conditions, the time for IO
      infusion was shorter than for IV infusion (65+/-17 vs 104+/-30s). The mean time
      saved by IO infusion over IV infusion was respectively 20+/-24s (P<0.001) and
      39+/-20s (P<0.001) under No-CBRN and CBRN conditions. CONCLUSION: The time to
      establish IO infusion was significantly shorter than that for peripheral IV
      infusion, under both No-CBRN and CBRN conditions. Further clinical studies are
      required to confirm that IO access would effectively save time over IV access in
      real pre-hospital emergency settings.

PMID- 19854555
TI  - A randomized controlled trial comparing the Arctic Sun to standard cooling for
      induction of hypothermia after cardiac arrest.
AB  - CONTEXT: Hypothermia improves neurological outcome for comatose survivors of out
      of-hospital cardiac arrest. Use of computer controlled high surface area devices
      for cooling may lead to faster cooling rates and potentially improve patient
      outcome. OBJECTIVE: To compare the effectiveness of surface cooling with the
      standard blankets and ice packs to the Arctic Sun, a mechanical device used for
      temperature management. DESIGN, SETTING, AND PATIENTS: Multi-center randomized
      trial of hemodynamically stable comatose survivors of out-of-hospital cardiac
      arrest. INTERVENTION: Standard post-resuscitative care inducing hypothermia using
      cooling blankets and ice (n=30) or the Arctic Sun (n=34). MAIN OUTCOME MEASURES:
      The primary end point was the proportion of subjects who reached a target
      temperature within 4h of beginning cooling. The secondary end points were time
      interval to achieve target temperature (34 degrees C) and survival to 3 months.
      RESULTS: The proportion of subjects cooled below the 34 degrees C target at 4h
      was 71% for the Arctic Sun group and 50% for the standard cooling group (p=0.12).
      The median time to target was 54 min faster for cooled patients in the Arctic Sun
      group than the standard cooling group (p<0.01). Survival rates with good
      neurological outcome were similar; 46% of Arctic Sun patients and 38% of standard
      patients had a cerebral performance category of 1 or 2 at 30 days (p=0.6).
      CONCLUSIONS: While the proportion of subjects reaching target temperature within
      4h was not significantly different, the Arctic Sun cooled patients to a
      temperature of 34 degrees C more rapidly than standard cooling blankets.

PMID- 19854556
TI  - Coagulopathy and traumatic shock: characterizing hemostatic function during the
      critical period prior to fluid resuscitation.
AB  - AIMS: Identifying early changes in hemostatic clot function as a result of tissue
      injury and hypoperfusion may provide important information regarding the
      mechanisms of traumatic coagulopathy. A combat-relevant swine model was used to
      investigate the development of coagulopathy during trauma by monitoring
      hemostatic function during increasing severity of shock. METHODS: Swine were
      injured (soft tissue+femur fracture) and hemorrhaged while continuously
      monitoring Oxygen Debt (OD) by indirect calorimetry at the airway. Hemostatic
      function was assessed by Thrombelastography (TEG), Prothrombin Time (PT), Partial
      Thromboplastin Time (PTT), and fibrinogen concentration and compared before
      hemorrhage (D0) and during shock when OD=40 and 80 ml/kg. An instrumented sham
      group was used for comparison. RESULTS: N=23 swine (N=18 hemorrhage, N=5 sham)
      weighing 45+/-6 kg were studied after removing an average of 34+/-14% of blood
      volume during hemorrhage. Hgb, Hct, platelet counts, PT and PTT did not change
      with increasing OD (p<0.05). Fibrinogen was reduced significantly by OD=40 ml/kg
      (mean diff.=-59.9 mg/dl, 95% CI diff. [-95.1, -24.6]). TEG parameters
      representing clot initiation (R) and polymerization (K and Alpha Angle) did not
      change with increasing OD during shock (p>0.053). Clot strength (MA) was reduced
      in the hemorrhage group by OD=80 ml/kg (mean diff.=-4.1mm, 95% CI diff. [-7.4, 
      0.8]). CONCLUSION: In this swine model of traumatic shock, fibrinogen was
      significantly reduced and an isolated reduction in clot strength (MA) was found
      with increasing OD. Fibrinogen consumption and altered platelet function may
      account for the earliest changes in hemostatic function during traumatic shock.

PMID- 19854557
TI  - The impact of Rapid Response System on delayed emergency team activation patient
      characteristics and outcomes--a follow-up study.
AB  - OBJECTIVE: To evaluate the impact of Rapid Response System (RRS) maturation on
      delayed Medical Emergency Team (MET) activation and patient characteristics and
      outcomes. DESIGN: Observational study. SETTING: Tertiary hospital. PATIENTS:
      Recent cohort of 200 patients receiving a MET review and early control cohort of
      400 patients receiving a MET review five years earlier at the start of RRS
      implementation. MEASUREMENTS AND RESULTS: We obtained information including
      demographics, clinical triggers for and timing of MET activation in relation to
      the first documented MET review criterion (activation delay) and patient
      outcomes. We found that patients in the recent cohort were older, more likely to
      be surgical and to have Not For Resuscitation (NFR) orders before MET review.
      Furthermore, fewer patients (22.0% vs. 40.3%, p<0.001) had delayed MET
      activation. When delayed activation occurred, there was a non-significant
      difference in its duration (early cohort: 12.0 [IQR 23.0]h vs. recent cohort: 9.0
      [IQR 20.5]h, p=0.554). Similarly, unplanned ICU admissions decreased from 31.3%
      to 17.3% (p<0.001). Delayed MET activation was independently associated with
      greater risk of unplanned ICU admission and hospital mortality (O.R. 1.79, 95%
      C.I. 1.33.-2.93, p=0.003 and O.R. 2.18, 95% C.I. 1.42-3.33, p<0.001,
      respectively). Being part of the recent cohort was independently associated with
      a decreased risk of delayed activation (O.R. 0.45, 95% C.I. 0.30-0.67, p<0.001)
      and unplanned ICU admission (O.R. 0.5, 95% C.I. 0.32-0.78, p=0.003). CONCLUSIONS:
      Maturation of a RRS is associated with a decrease in the incidence of unplanned
      ICU admissions and MET activation delay. Assessment of a RRS early in the course
      of its implementation may underestimate its efficacy.

PMID- 19854558
TI  - Controlled gating of lysenin pores.
AB  - Lysenin forms unitary large conductance pores in artificial bilayer membranes
      containing sphingomyelin. A population of lysenin pores inserted into such a
      bilayer membrane exhibited a dynamic negative conductance region, as predicted by
      a simple two-state model for voltage-gated channels. The recorded I-V curves
      demonstrated that lysenin pores inserted into the bilayer are uniformly oriented.
      Additionally, the transition between the two-states was affected by changes in
      the monovalent ion concentration and pH, pointing towards an electrostatic
      interaction governing the gating mechanism.

PMID- 19854559
TI  - Analysis of light-induced transmembrane ion gradients and membrane potential in
      Photosystem I proteoliposomes.
AB  - Photosystem I (PSI) complexes can support a light-driven electrochemical gradient
      for protons, which is the driving force for energy-conserving reactions across
      biological membranes. In this work, a computational model that enables a
      quantitative description of the light-induced proton gradients across the
      membrane of PSI proteoliposomes is presented. Using a set of electrodiffusion
      equations, a compartmental model of a vesicle suspended in aqueous medium was
      studied. The light-mediated proton movement was modeled as a single proton
      pumping step with backpressure of the electric potential. The model fits
      determinations of pH obtained from PSI proteoliposomes illuminated in the
      presence of mediators of cyclic electron transport. The model also allows
      analysis of the proton gradients in relation to the transmembrane ion fluxes and
      electric potential. Sensitivity analysis enabled a determination of the
      parameters that have greater influence on steady-state levels and onset/decay
      rates of transmembrane pH and electric potential. This model could be used as a
      tool for optimizing PSI proteoliposomes for photo-electrochemical applications.

PMID- 19854560
TI  - Using penalty functions to evaluate aggregation models for environmental indices.
AB  - The purpose of indices is to summarize a large volume of information into a
      single number that is easy to understand and interpret. Environmental indices
      provide a composite picture of an environmental condition derived from a series
      of observed measurements and parameters. They are used as communication tools by
      regulatory agencies to characterize the state of a specific environmental system
      (air, water, and sediments) and to study the impact of regulatory policies on
      various environmental management practices. In the development of environmental
      indices, a few issues and problems have been encountered arising as a result of
      the abstraction of information and data. These problems are referred to as
      characteristic properties that include ambiguity, eclipsing, compensation and
      rigidity. These characteristic properties have long been identified and
      interpreted in Boolean (e.g., Yes/No) or qualitative (e.g., low, medium, high)
      terms. In this paper, we propose a new approach to describe the above stated
      characteristic properties on a continuous scale to evaluate and compare the
      behavior of various aggregation models. Our approach is based on developing
      penalty functions for each characteristic property. A water quality index example
      by Swamee and Tyagi (2000) is used to explain our approach. A detailed case study
      for a developing microbial risk index is also provided to show how the proposed
      approach can be extended to complex hierarchical systems. Results show that it is
      possible to improve aggregation models for index development. Future research
      directions to improve index development are also discussed.

PMID- 19854561
TI  - Impacts of experimental trampling on tall alpine herbfields and subalpine
      grasslands in the Australian Alps.
AB  - The Australian Alps, which are of high conservation value, are popular summer
      bushwalking destinations. Experimental trampling trials using a standardized
      methodology were conducted to determine the resistance and resilience of the two
      common vegetation types: tall alpine herbfield and subalpine grasslands.
      Vegetation parameters were measured in lanes subject to control (no trampling),
      30, 100, 200, 500 and 700 passes at five sites prior to trampling, immediately
      post trampling, 2 weeks, 6 weeks and 1 year post trampling. Vegetation height,
      cover of graminoids and herbs, as well as net species richness all declined with
      trampling, while litter cover increased. Thresholds for damage varied between the
      two communities and among the different vegetation parameters. The resistance
      indices for the two communities (number of passes resulting in 50% reduction in
      vegetation cover), however, were similar at around 440-450 passes indicating that
      these two communities are among the most resistant of the 19 alpine-subalpine
      communities that have been tested around the world, but only of moderate
      resistance compared to non-alpine communities. The two communities showed limited
      recovery with damage still evident 1 year post trampling. This indicates that
      they have only moderate tolerance to damage due to moderate resistance, but low
      resilience.

PMID- 19854562
TI  - Tissue motion and strain in the human brain assessed by intraoperative ultrasound
      in glioma patients.
AB  - The objective of the study was to investigate tissue motion and strain imposed by
      cardiovascular pulsation in pathologic and normal brain parenchyma, as quantified
      from in vivo ultrasound data. Ultrasound acquired during surgery of 16 patients
      with glial tumors was retrospectively processed and analyzed. The tissue velocity
      was quantified at depths of 1cm, 2cm and 3cm from brain cortex to investigate
      spatial dependency with depth. Comparison of strain and velocity in tumor and
      adjacent normal parenchyma was performed by selecting two regions-of-interest in
      the hyperechoic tumor and two regions in the low-echogenic areas interpreted as
      mainly normal tissue with some degree of tumor cell infiltration. The absolute
      maximum tissue velocity is seen to increase with increasing depths in 14 of 16
      cases (87.5%). The maximum tissue velocities in the four regions close to the
      ultrasound visible tumor border are not statistically different (p=0.163 to
      p=0.975). The strain magnitudes are significantly higher in the regions with
      expected normal brain parenchyma than in regions with expected glial tumor
      tissue, both for the two regions being closest to the tumor border (p=0.0004) and
      for the two regions further away from the tumor border (p=0.0009). We conclude
      that the velocity of the brain parenchyma imposed by arterial pulsation during a
      cardiac cycle is generally increasing with increasing depth from cortex. The
      maximum velocity appears to be similar in regions with expected normal brain and
      tumor tissue, thus, does not seem to be affected by pathology. Strain magnitude
      is, however, a suitable parameter for discrimination of glial tumor and normal
      brain parenchyma. (E-mail: Tormod.Selbekk@sintef.no).

PMID- 19854563
TI  - Noninvasive thrombolysis using pulsed ultrasound cavitation therapy -
      histotripsy.
AB  - Clinically available thrombolysis techniques are limited by either slow
      reperfusion (drugs) or invasiveness (catheters) and carry significant risks of
      bleeding. In this study, the feasibility of using histotripsy as an efficient and
      noninvasive thrombolysis technique was investigated. Histotripsy fractionates
      soft tissue through controlled cavitation using focused, short, high-intensity
      ultrasound pulses. In vitro blood clots formed from fresh canine blood were
      treated by histotripsy. The treatment was applied using a focused 1-MHz
      transducer, with five-cycle pulses at a pulse repetition rate of 1kHz. Acoustic
      pressures varying from 2 to 12MPa peak negative pressure were tested. Our results
      show that histotripsy can perform effective thrombolysis with ultrasound energy
      alone. Histotripsy thrombolysis only occurred at peak negative pressure >or=6MPa
      when initiation of a cavitating bubble cloud was detected using acoustic
      backscatter monitoring. Blood clots weighing 330mg were completely broken down by
      histotripsy in 1.5 to 5min. The clot was fractionated to debris with >96% weight
      smaller than 5mum diameter. Histotripsy thrombolysis treatment remained effective
      under a fast, pulsating flow (a circulatory model) as well as in static saline.
      Additionally, we observed that fluid flow generated by a cavitation cloud can
      attract, trap and further break down clot fragments. This phenomenon may provide
      a noninvasive method to filter and eliminate hazardous emboli during
      thrombolysis.

PMID- 19854564
TI  - Narrowing of the middle cerebral artery: artificial intelligence methods and
      comparison of transcranial color coded duplex sonography with conventional TCD.
AB  - The goal of the study was to compare performances of transcranial color-coded
      duplex sonography (TCCS) and transcranial Doppler sonography (TCD) in the
      diagnosis of the middle cerebral artery (MCA) narrowing in the same population of
      patients using statistical and nonstatistical intelligent models for data
      analysis. We prospectively collected data from 179 consecutive routine digital
      subtraction angiography (DSA) procedures performed in 111 patients (mean age
      54.17+/-14.4 years; 59 women, 52 men) who underwent TCD and TCCS examinations
      simultaneously. Each patient was examined independently using both ultrasound
      techniques, 267 M1 segments of MCA were assessed and narrowings were classified
      as < or =50% and >50% lumen reduction. Diagnostic performance was estimated by
      two statistical and two artificial neural networks (ANN) classification methods.
      Separate models were constructed for the TCD and TCCS sonographic data, as well
      as for detection of "any narrowing" and "severe narrowing" of the MCA. Input for
      each classifier consisted of the peak-systolic, mean and end-diastolic velocities
      measured with each sonographic method; the output was MCA narrowing. Arterial
      narrowings less or equal 50% of lumen reduction were found in 55 and >50%
      narrowings in 26 out of 267 arteries, as indicated by DSA. In the category of
      "any narrowing" the rate of correct assignment by all models was 82% to 83% for
      TCCS and 79% to 81% for TCD. In the diagnosis of >50% narrowing the overall
      classification accuracy remained in the range of 89% to 90% for TCCS data and 90%
      to 91% for TCD data. For the diagnosis of any narrowing, the sensitivity of the
      TCCS was significantly higher than that of the TCD, while for diagnosis of >50%
      MCA narrowing, sensitivity of the TCCS was similar to sensitivity of the TCD. Our
      study showed that TCCS outperforms conventional TCD in detection of < or =50% MCA
      narrowing, whereas no significant difference in accuracy between both methods was
      found in the diagnosis of >50% MCA narrowing. (E-mail:
      jaroslaw.krejza@uphs.upenn.edu).

PMID- 19854565
TI  - Performance of two dimensional displacement and strain estimation techniques
      using a phased array transducer.
AB  - The goal of this study was to investigate the applicability of conventional 2-D
      displacement and strain imaging techniques to phased array radiofrequency (RF)
      data. Furthermore, the possible advantages of aligning and stretching techniques
      for the reduction of decorrelation artefacts was examined. Data from both
      realistic simulations and phantoms were used in this study. Recently, the used
      processing concepts were successfully applied to linear array data. However,
      their applicability to sector scan data is not trivial because of the polar grid.
      Homogeneous and inhomogeneous tissue phantoms were simulated at a range of
      strains (0 to 5%) using Field II((c)). The inhomogeneous phantom, a commonly used
      tumor/lesion model, was also constructed using gelatin/agar solutions. A coarse
      to-fine displacement algorithm was applied, using aligning and stretching to
      enhance re-correlation. Vertical and horizontal strains were reconstructed from
      the axial and lateral displacements. Results revealed that the error on
      displacement estimates was lower when using 2-D data windows rather than 1-D
      windows. For regions at large depths and large insonification angles, the allowed
      lateral window size was limited. Still, 1-D windows resulted in larger errors.
      The re-correlation techniques resulted in a significant increase in the
      elastographic signal-to-noise ratio (SNRe) and elastographic contrast-to-noise
      ratio (CNRe) of the vertical and horizontal strain components. An increase of the
      SNRe of 5-20 dB was observed over a range of strains (0.5 to 5.0%). In the
      inhomogeneous phantom, a vertical SNRe of 27.7 dB and a horizontal SNRe of 16.7
      dB were measured in the background. The vertical and horizontal CNRe were 35 dB
      and 23.1 dB, respectively. For the experimental data, lower SNRe (vertical: 19.1
      dB; horizontal: 11.4 dB) and CNRe (vertical: 33.3 dB; horizontal: 12.5 dB) were
      found. In conclusion, 2-D window matching of sector scan data is feasible and
      outperforms 1-D window matching. Furthermore, the use of re-correlation
      techniques enhances both precision and contrast of strain images.

PMID- 19854566
TI  - Multichannel pulsed Doppler signal processing for vascular measurements in mice.
AB  - The small size, high heart rate and small tissue displacement of a mouse require
      small sensors that are capable of high spatial and temporal tissue displacement
      resolutions and multichannel data acquisition systems with high sampling rates
      for simultaneous measurement of high fidelity signals. We developed and evaluated
      an ultrasound-based mouse vascular research system (MVRS) that can be used to
      characterize vascular physiology in normal, transgenic, surgically altered and
      disease models of mice. The system consists of multiple 10/20MHz ultrasound
      transducers, analog electronics for Doppler displacement and velocity
      measurement, signal acquisition and processing electronics and personal computer
      based software for real-time and off-line analysis. In vitro testing of the
      system showed that it is capable of measuring tissue displacement as low as
      0.1mum and tissue velocity (mum/s) starting from 0. The system can measure blood
      velocities up to 9m/s (with 10MHz Doppler at a PRF of 125kHz) and has a temporal
      resolution of 0.1 milliseconds. Ex vivo tracking of an excised mouse carotid
      artery wall using our Doppler technique and a video pixel tracking technique
      showed high correlation (R(2)=0.99). The system can be used to measure diameter
      changes, augmentation index, impedance spectra, pulse wave velocity,
      characteristic impedance, forward and backward waves, reflection coefficients,
      coronary flow reserve and cardiac motion in murine models. The system will
      facilitate the study of mouse vascular mechanics and arterial abnormalities
      resulting in significant impact on the evaluation and screening of vascular
      disease in mice.

PMID- 19854567
TI  - Fibrinolytic effects of transparietal ultrasound associated with intravenous
      infusion of an ultrasound contrast agent: study of a rat model of acute cerebral
      stroke.
AB  - The aim of this study was to evaluate the thrombolytic effect of focused
      transparietal ultrasound in combination with a specific contrast agent
      (microbubbles) in acute cerebral ischemia. Acute cerebral ischemia was induced in
      10 rats by intra-arterial clots injection. Five rats (group 1) were treated with
      a combination of transparietal ultrasound (probe 2 MHz, acoustic power 500
      mW/cm(2)) and intravenous injection of 0.6 mL of the ultrasound contrast agent
      (UCA) sulfur hexafluoride. Five rats (group 2) were treated by fibrinolytic
      intravenous infusion (recombinant tissue plasminogen activator). Cerebral
      cellular energy production was determined by measuring the cellular
      phosphorylation using phosphorus magnetic spectroscopy before and during ischemia
      induction and after treatment. Measures were performed on a dedicated 2.35T
      magnet. The ratio phosphocreatine (P(Cr)) on inorganic phosphate (P(i)),
      P(Cr)/P(i), estimation of the oxidative phosphorylation metabolism and the
      intracellular pH (pHi) were measured in the two groups. Compared with the
      ischemia induction period, both treatments were associated with an increase of
      P(Cr)/P(i) and pHi values, respectively, +80% and +100% in group 1 (p=0.07) and
      +100% and +80% in group 2 (p=0.04). There was no significant difference between
      the two groups for the response treatment. To conclude, treatment with
      intravenous fibrinolytic infusion and treatment with focused ultrasound in
      combination with UCA seems to be equally effective in treating acute cerebral
      ischemia in rats. (E-mail: j.p.tasu@chu-poitiers.fr).

PMID- 19854568
TI  - Open to debate. The motion: Cryotherapy is an efficient alternative for kidney
      cancer.

PMID- 19854569
TI  - Kinetic study of the oxidation and nitration of catechols in the presence of
      nitrous acid ionization equilibria.
AB  - Conversion of catechols to corresponding nitro derivatives in the presence of
      nitrous acid dissociation is studied using voltammetry and UV-vis
      spectrophotometry. The results indicate that the quinones derived from oxidation
      of catechols by nitrous acid participate in Michael addition reaction with
      nitrite ion in very mild acidic solutions. Rank annihilation factor analysis RAFA
      is applied to resolve the two-way kinetic spectra data measured from
      spectroscopic reactions. The rank of the original data matrix is reduced by one
      by annihilating the information of each component. It is shown that both
      reactions are drastically depends on pH and nitrous acid or nitrite ion
      percentage. The rate constants of oxidation and nitration reactions of catechol
      derivatives are obtained at the pHs around pK(a) of nitrous acid.

PMID- 19854570
TI  - Tyre char preparation from waste tyre rubber for dye removal from effluents.
AB  - A number of chars from waste tyre rubber were prepared by carbonisation at 673
      1173 K. The effects of holding time, heating rate and particle size on the
      textural characteristics and elemental composition of the resultant chars were
      investigated. It was demonstrated that temperatures over 773 K did not have a
      significant improvement on the total surface area but resulted in lower char
      yields following increased aromatisation. Modelling of dye adsorption isotherms
      showed that the Redlich-Peterson expression yields the best-fit between
      experimental and predicted data. Furthermore, for a larger sized dye like Acid
      Yellow 117 (MW=848 g/mol), the amount adsorbed by the tyre char is not directly
      proportional to the total surface area when compared with a commercial carbon,
      revealing that factors other than total surface area are involved in the
      adsorption potential of the tyre chars.

PMID- 19854571
TI  - Mineralization of reactive Black 5 in aqueous solution by ozone/H2O2 in the
      presence of a magnetic catalyst.
AB  - Particles are often too small to be separated from a reaction system and
      recycled, especially in wastewater treatment via a catalytic ozonation process.
      Thus, the objective of this study was to prepare a magnetic catalyst
      (SiO(2)/Fe(3)O(4)) that can be recycled by using an external magnetic field. The
      effects of the characteristics of the magnetic catalyst, pH values, catalyst
      dosage, and initial concentration of Reactive Black 5 (RB5) on mineralization
      efficiency of the magnetic catalyst/H(2)O(2)/O(3) process were also investigated.
      The mineralization efficiency of RB5 under various conditions followed the
      sequence: SiO(2)/Fe(3)O(4)/H(2)O(2)/O(3)>SiO(2)/Fe(3)O(4)/O(3)>Fe(3)O(4)/O(3)
      approximately H(2)O(2)/O(3)>O(3)>SiO(2)/Fe(3)O(4)/H(2)O(2). Given the results of
      our reuse and recovery experiments, the magnetic catalyst shows considerable
      promise for use in water treatment.

PMID- 19854572
TI  - On the retention of uranyl and thorium ions from radioactive solution on peat
      moss.
AB  - The efficiency of the radioactive uranyl and thorium ions on the peat moss from
      aqueous solutions has been investigated under different experimental conditions.
      The sorption and desorption of uranyl and thorium ions on three types (unmodified
      peat moss, peat moss treated with HNO(3) and peat moss treated with NaOH) of peat
      moss were studied by the static method. Peat moss was selected as it is available
      in nature, in any amount, as a cheap and accessible sorbent. Study on desorption
      of such ions led to the conclusion that the most favourable desorptive reagent
      for the uranyl ions is Na(2)CO(3) 1M while, for the thorium ions is HCl 1M. The
      results obtained show that the parameters here under investigation exercise a
      significant effect on the sorption process of the two ions. Also, the
      investigations performed recommend the peat moss treated with a base as a
      potential sorbent for the uranyl and thorium ions from a radioactive aqueous
      solution.

PMID- 19854574
TI  - Influences of major nutrient elements on Pb accumulation of two crops from a Pb
      contaminated soil.
AB  - To know about the effect of major nutrient elements on various forms of Pb and
      metal extraction, a greenhouse experiment was conducted to assess the effects of
      various major nutrient elements on Pb accumulation in two crops (Spinacia
      oleracea, SO and Sonchus arvensis, SA) in Changchun, China. Results indicated
      that, for SO, the Pb concentrations in both shoots and roots had no difference
      with increasing nutrients except for low nutrient treatment (1/2H). For SA, high
      nutrient treatments (2H and 3H) resulted in higher Pb concentrations in roots
      than low and standard nutrient treatments (1/2H and C), but high Pb concentration
      in shoot appeared in low and highest nutrient treatments (1/2H and 3H). The
      nitrogenous nutrient treatment (2N) had the most effect of increasing Pb
      concentrations in roots of SO and SA. The potassic and phosphorus nutrient
      treatments (2K and 2P) had little effect on the Pb concentrations in plant
      tissues for SO. Pb concentration in SO was lower than SA. Because of the higher
      total biomass in SO than SA, the ability to Pb accumulation in SO was better than
      SA. Sequential extraction results indicated that the addition of soil amendments
      transform soil Pb from bioavailable fractions to non-bioavailable fraction
      substantially. The results suggest that nitrogen fertilizer for SO and phosphorus
      fertilizer for SA are the most effective materials for the remediation of Pb
      contaminated soils, and increase the tolerance of crops to Pb contamination.

PMID- 19854573
TI  - Mechanism and kinetics of parathion degradation under ultrasonic irradiation.
AB  - The parathion degradation under ultrasonic irradiation in aqueous solution was
      investigated. The results indicate that at the conditions in question,
      degradation rate of parathion decreased with increasing initial concentration and
      decreasing power. The optimal frequency for parathion degradation was 600 kHz.
      The free radical reactions predominate in the sonochemical degradation of
      parathion and the reaction zones are predominately at the bubble interface and,
      to a much lesser extent, in bulk solution. The gas/liquid interfacial regions are
      the real effective reaction sites for sonochemical degradation of parathion. The
      reaction can be well described as a gas/liquid heterogeneous reaction which obeys
      a kinetic model based on Langmuir-Hinshelwood model. The main pathways of
      parathion degradation by ultrasonic irradiation were also proposed by qualitative
      and quantitative analysis of organic and inorganic byproducts. It is indicated
      that the N(2) in air takes part in the parathion degradation through the
      formation of NO(2) under ultrasonic irradiation. Parathion is decomposed into
      paraoxon and 4-nitrophenol in the first step via two different pathways,
      respectively, which is in agreement with the theoretical molecular orbital (MO)
      calculations.

PMID- 19854575
TI  - Differences in short-term primary motor cortex synaptic potentiation as assessed
      by repetitive transcranial magnetic stimulation in migraine patients with and
      without aura.
AB  - To find out more about glutamatergic and gabaergic transmission in migraine, in
      this study we investigated glutamate-dependent short-term synaptic potentiation
      and GABA-dependent inhibitory cortical interneuron excitability as assessed by
      5Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP,
      amplitude facilitation and cortical silent period, CSP, duration lengthening) in
      migraine patients with (MA) and without aura (MwoA) and healthy controls. We
      studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control
      subjects. 5Hz-rTMS was delivered at 120% resting motor threshold to the hand
      motor area of the left hemisphere with the target muscle at rest and during
      contraction. Three of the MA patients were also tested at the end of visual aura
      during a spontaneous migraine attack. ANOVA showed that the MEP significantly
      increased in size and CSP significantly lengthened during 5Hz-rTMS in the three
      groups tested. The 5Hz-rTMS-induced MEP facilitation differed significantly being
      highest in MA patients. In the three patients tested both ictally and
      interictally the MEP increased during the interictal session but remained
      unchanged when the visual aura ended. Our study shows that the neurophysiological
      feature that differentiates MA patients from MwoA patients and healthy controls
      is an abnormal M1 susceptibility to 5Hz-rTMS both outside and during the attack
      suggesting that glutamate-dependent short-term M1 cortical potentiation patterns
      differ in migraine with and without aura.

PMID- 19854576
TI  - The Nociception Coma Scale: a new tool to assess nociception in disorders of
      consciousness.
AB  - Assessing behavioral responses to nociception is difficult in severely brain
      injured patients recovering from coma. We here propose a new scale developed for
      assessing nociception in vegetative (VS) and minimally conscious (MCS) coma
      survivors, the Nociception Coma Scale (NCS), and explore its concurrent validity,
      inter-rater agreement and sensitivity. Concurrent validity was assessed by
      analyzing behavioral responses of 48 post-comatose patients to a noxious
      stimulation (pressure applied to the fingernail) (28 VS and 20 MCS; age range 20
      82 years; 17 of traumatic etiology). Patients' were assessed using the NCS and
      four other scales employed in non-communicative patients: the 'Neonatal Infant
      Pain Scale' (NIPS) and the 'Faces, Legs, Activity, Cry, Consolability' (FLACC)
      used in newborns; and the 'Pain Assessment In Advanced Dementia Scale' (PAINAD)
      and the 'Checklist of Non-verbal Pain Indicators' (CNPI) used in dementia. For
      the establishment of inter-rater agreement, fifteen patients were concurrently
      assessed by two examiners. Concurrent validity, assessed by Spearman rank order
      correlations between the NCS and the four other validated scales, was good.
      Cohen's kappa analyses revealed a good to excellent inter-rater agreement for the
      NCS total and subscore measures, indicating that the scale yields reproducible
      findings across examiners. Finally, a significant difference between NCS total
      scores was observed as a function of diagnosis (i.e., VS or MCS). The NCS
      constitutes a sensitive clinical tool for assessing nociception in severely brain
      injured patients. This scale constitutes the first step to a better management of
      patients recovering from coma.

PMID- 19854577
TI  - Histopathological and clinical investigations in Neospora caninum experimentally
      infected broiler chicken embryonated eggs.
AB  - To date, despite the limited information about the role of birds in Neospora
      caninum infection, there are no reports regarding the role of broiler chickens.
      In the present study, an experimental infection with N. caninum NC-1 isolate was
      conducted in embryonated eggs from 70 Lohman broiler chickens randomly divided
      into seven equal groups. At 8 days of incubation, six groups were inoculated via
      chorioallantoic (CA) liquid with different dilutions (10, 10(2), 10(3), 10(4),
      10(5), and 10(6)) of tachyzoites/embryonated egg. The 7th group was considered
      the control. The mortality rate, gross and histopathologic changes of tissues of
      the dead embryos and live hatched chickens up to 60 days old were studied and
      evaluated. There were no hatchings in groups with 10(5) and 10(6) tachyzoites. In
      groups with 10, 10(2), 10(3) and 10(4) tachyzoites there were 8, 7, 5 and 2
      hatchings, respectively. From the surviving chickens only one 10(4) tachyzoites
      inoculated chicken showed clinical neurologic signs. In all groups the main gross
      lesions were hemorrhage associated with thickening of the CA membranes. Three
      chickens (one chicken with 10(4) tachyzoites and two with 10(5) tachyzoites)
      showed arthritis in the feet joints after two weeks of inoculation. Microscopic
      examination of the heart, liver and chorioallantoic membrane revealed acute
      neosporosis and, in some cases, granulomatous inflammation. Our findings implied
      that broiler chicken embryonated egg is a completely suitable animal model for
      biological studies of acute neosporosis studies and genetic susceptibility can be
      propounded in different chicken breeds. It seems 10(3) tachyzoites dilution is
      equal to LD50 in N. caninum infection in broiler chicken embryonated eggs and can
      be used in other experimental investigations.

PMID- 19854578
TI  - Cutaneous microcirculatory assessment of the burn wound is associated with depth
      of injury and predicts healing time.
AB  - RATIONALE: Current trends for the treatment of deep partial thickness and full
      thickness burns include early excision and skin grafting. In this study we
      retrospectively evaluated the ability of Laser Doppler Flowmetry (LDF), taken
      within 24h of the burn to predict: (1) burn wound depth and (2) wounds which
      would heal in less than 21 days. METHOD: The Laser Doppler Flowmeter (O2C, LEA
      Medizintechnik, Germany) was employed to non-invasively measure the cutaneous
      microcirculation of 173 selected areas on 28 patients who suffered burns.
      RESULTS: A distinct association between initial flow (<24h after burn injury) and
      the clinical assessment of depth of burn wounds was observed. Wounds
      demonstrating an initial blood flow of >100 AU were, in 93.1% of cases, correctly
      (positively) predicted for spontaneous healing within 21 days. A blood flow of
      <100 AU (negatively) predicted in 88.2%, those wounds which would not go on to
      heal within 21 days. Sequential measurement analysis (<24h, 3 days after injury
      and 6 days after injury) revealed no significant decrease in skin perfusion
      velocity or flow rate. CONCLUSION: LDF can provide immediate results for early
      determination of burn wound depth and is useful in selecting patients for
      conservative treatment of their burn wounds.

PMID- 19854579
TI  - The year in burns 2008.
AB  - For 2008, approximately 1200 original burn research articles were published in
      scientific journals using the English language. This article reviews those with
      the most impact on burn treatment according to the Editor of one of the major
      journals (Burns). As in the previous year's review, articles were divided into
      the following topic areas: epidemiology, wound characterisation, critical care
      physiology, inhalation injury, infection, metabolism and nutrition, psychological
      considerations, pain management, rehabilitation, and burn reconstruction. Each
      selected article is mentioned briefly with editorial comment.

PMID- 19854580
TI  - Possible key role of immune system in Schmorl's nodes.
AB  - Schmorl's nodes (SNs) are common abnormalities in the human spine, which
      represent herniation of the nucleus pulposus of the intervertebral disc into the
      adjacent cartilaginous endplate of the vertebra. However, the principle mechanism
      of SNs is still not fully understood. And the relationship of SNs in the spine
      and their clinical significance as a source of low back pain in the general
      population remains unknown. It is therefore important to get better understanding
      of this. Here, we review the clinical and experiment evidence on inducing of the
      SNs and correlative back pain, and propose a possible mechanism. Studies showed
      that once the nucleus pulposus enters into vascular tissue, the immune system
      could recognize it as a foreign body, and induces the immunological reaction.
      Then, there would be osteoimmunology action, a crosstalk between the immune
      system and bone, leading to bone loss by dysregulating T-lymphocyte function, and
      resulting to the bone absorption. Furthermore, the cytokines are involved in the
      development of immunological reactions and could be responsible for the
      significant pathology of symptomatic SNs. Given the above background, we
      hypothesize that immune system could be a key role in SNs and result in the pain.

PMID- 19854581
TI  - Pseudo myocardial infarction - a condition in need to be redefined?
AB  - Since the introduction of cardiac plasma troponin measurements, a significant
      number of patients were seen with chest pain, elevated troponin levels but no
      significant coronary artery disease. Pulmonary embolism, aortic valve disease,
      myocarditis, sepsis, trauma, arrythmias, stress cardiomyopathy and dilated
      cardiomyopathy stand among possible causes for this syndrome. In some cases,
      myocardial strain could be the mechanism underlying this phenomenon, since it is
      known that the stimulation of stretch-responsive integrins may lead to the
      release of cardiac troponin I. In the present text, a case is made in favour of
      classifying this syndrome, of chest pain with increased values for plasma cardiac
      troponin, with or without ECG changes, in the absence of definite myocardial
      infarction or coronary artery disease, as pseudo myocardial infarction (PMI).
      This constitutes a new definition for a concept with decades, formerly centered
      on clinical and electrocardiographic changes mimicking infarct. The case is based
      on the search of scientific truth, on avoidance of unnecessary cardiac
      examinations, on avoidance of unnecessary drug therapy and on avoidance of
      unnecessary legal liability. PMI should be seen as a working diagnosis, since a
      more definitive diagnosis can be reached at all time. It should also be seen as a
      heterogeneous group of patients - several different diseases and conditions can
      lead to this phenomenon. But it must certainly not be seen as a benign condition,
      since published studies point in a totally different direction.

PMID- 19854582
TI  - [Should patients infected with HIV be screened for occult hepatitis B?].
AB  - Occult hepatitis B is defined as the presence of hepatitis B virus (HBV) DNA in
      the absence of detectable HBs antigen. The prevalence of occult hepatitis B among
      patients HIV-infected is uncertain, varying between 0% and 89%, and the clinical
      consequences of the coinfection are poorly known. The aim of this study was to
      evaluate the frequency of occult hepatitis B among HIV-infected patients and
      determine risk factors. METHODS: This retrospective study was conducted with
      plasma samples from 31HIV-infected patients untreated for HBV infection and for
      whom at least one sample was available. All patients were found to be carriers of
      isolated anti-HBc antibodies between 2000 and 2008, and HBV DNA was quantified in
      51 samples (one to three per patient) by real-time PCR using the Qiagen HBV PCR
      kit. RESULTS: HBV DNA was found in samples from seven patients (22%). Occult
      hepatitis B seemed to be more frequent among patients coinfected with HCV
      (p=0.047). The number of CD4 cells was significantly less in samples containing
      detectable HBV DNA than in those with no detectable HBV DNA. CONCLUSION: The
      prevalence of occult hepatitis B seemed high, and HBV DNA titers were weak (<
      20UI/mL), among patients infected with HIV and carrying isolated anti-HBc
      antibodies. These results would support screening HIV-infected patients for the
      presence of HBV DNA if confirmed with a larger patient population.

PMID- 19854584
TI  - [Antimicrobial blood concentrations in burns. A five years' retrospective
      survey].
AB  - The monitoring of antimicrobial agents is a routine in our unit. We reviewed the
      results either of peak-and-through concentrations (peak and through is one
      sample) or concentrations at steady state (Css) of all antimicrobials given over
      five years (2001 to 2005) and studied the antimicrobials with at least 20
      samples. We found 706 samples in 122 patients, the antimicrobials being amikacin,
      amoxicillin, ceftazidime, ciprofloxacin, cloxacillin, gentamicin, imipenem,
      ofloxacin, tobramycin and vancomycin. When comparing samples in witch the
      concentrations were above a value thought to be predictive of efficacy to those
      were not, we could notice: that no parameter about patients or burn surface was
      predictable for achieving targeted blood concentration; that usual regimen could
      not achieve targeted concentrations, excepted with ceftazidime, provided it was
      used in continuous infusion; that, with the other beta-lactams, continuous
      infusion was more likely to achieve targeted blood concentrations; that, with
      fluoroquinolones, both higher and more frequent injections were needed; that,
      with aminoglycosides used once a day, the dosage had to be higher than usually
      recommended. We conclude that antimicrobial regimen should be altered in burns
      and that a monitoring of blood concentrations should be performed in these
      patients.

PMID- 19854583
TI  - [Human African trypanosomiasis in mangrove epidemiologic area. Presentation,
      diagnosis and treatment in Guinea, 2005-2007].
AB  - Gambiense human African trypanosomiasis is still assumed to be endemic in many
      part of West Africa, particularly in Guinea coastal area with mangrove swamp.
      Diagnosis is usually made during active medical screening or by passive
      initiative. OBJECTIVES: To describe clinical and epidemiological characteristics
      of Gambiense human African trypanosomiasis in the coastal area of Guinea.
      METHODS: Exhaustive and retrospective analysis of all patients attending the
      trypanosomiasis center in the coastal area of Guinea between January 2005 and
      December 2007 with a diagnosis of human African trypanosomiasis. RESULTS: A total
      of 196 patients were recruited for the study. Out of them, 55 % of the 73
      patients diagnosed during active screening were classified stage 1
      (haemolymphatic stage) or early stage 2 (meningoencephalitic stage). Contrarily,
      115 of the 120 diagnosed by passive procedure were classified late stage 2, which
      features more specific signs and neurological symptoms, and leads to coma and
      death. More than 90 % of all cases presented cervical lymph nodes with
      identification of trypanosome on direct examination of fluid puncture. Less than
      one third of the patients were reexamined three months later. DISCUSSION: In the
      coastal area of Guinea with mangrove swamp, direct examination of lymph node
      fluid puncture seems to be the most contributive test for the diagnosis of human
      African trypanosomiasis. Hence, associating clinical examination of cervical
      lymph nodes area and direct examination of fluid puncture may allow an early
      diagnosis of Gambiense human African trypanosomiasis and favor the implementation
      of efficient therapeutic strategies.

PMID- 19854585
TI  - [1997-2007, 10 years of monitoring the evolution of resistance of Streptococcus
      pneumoniae to antibiotics in the region Centre; review of the Pneumococcus
      network].
AB  - Regional pneumococcal observatories in region Centre, created in 1997,
      participate with the others pneumococcal observatories alongside the National
      Reference Center for Pneumococci and the Institut de Veille Sanitaire at the
      monitoring of the evolution of resistance of pneumococci to antibiotics in
      France. Between 1997 and 2007, 2427 strains of Streptococcus pneumoniae were
      isolated in part from cerebrospinal fluids, blood and middle ear fluid, from
      children and adults. The prevalence of pneumococci with a decreased
      susceptibility to penicillin (PDSP) decreased strongly in region Centre: 56.8 %
      in 2001, 39.6 % en 2007. These data are similar to the French national data over
      the same period.

PMID- 19854586
TI  - [KPC carbapenemases: what is at stake in clinical microbiology?].
AB  - Emergence and dissemination of carbapenem resistance in the world represent a
      significant threat for management of hospital-acquired infections. From the early
      2000s, Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases (KPC)
      have initially been reported from the USA and now worldwide, becoming the most
      important carbapenemase. These KPC producing-bacteria are mostly involved in
      nosocomial and systemic infections. They are mostly Enterobacteriaceae and more
      rarely Pseudomonas aeruginosa. KPC beta-lactamases confer decreased
      susceptibility or resistance to virtually all beta-lactams. Therefore,
      carbapenems (imipenem, meropenem, ertapenem) may become inefficient for treating
      enterobacterial infections with KPC-producing bacteria, which are in addition
      resistant to many other non beta-lactam molecules, leaving only few available
      therapeutic options. Detection of KPC-producing bacteria may be difficult based
      on routine antibiotic susceptibility testing. Several phenotypic tests have been
      proposed, but until now, only molecular methods are reliable techniques for their
      identification. It is therefore critical to implement efficient infection control
      measures to detect patients who are colonized or infected with these pathogens in
      order to limit their spread.

PMID- 19854588
TI  - [Evolution of third-generation cephalosporin resistance in Enterobacteriaceae
      from 2000 to 2008 in a Perpignan hospital].
AB  - The aim of this work was to evaluate the evolution of Enterobacteriaceae
      resistance to third generation cephalosporin (3CG) from 2000 to 2008 at Perpignan
      hospital. Were observed: the percentage of strains isolated from short stay
      wards, intensive care unit and medium and long-term care facility. The percentage
      of strains isolated from: urine, suppuration, tracheal aspiration, and blood have
      been evaluated. The proportion of Escherichia coli (E. coli) strains among the
      Enterobacteriaceae strains intermediate (I) or resistant (R) to 3GC was also
      evaluated.The number of Enterobacteriaceae intermediated (I) or resistant (R) to
      3GC increased (402 %).The distribution of species I or R to 3GC has changed,
      decrease of Klebsielle pneumoniae and Enterobacter aeorogenes species,
      Escherichia.coli and Enterobacter cloacae became dominant in 2008. We noted the
      change of isolated species distribution, urines represent the main source of
      multiresistant Enterobacteriaceae (MRE), 72 % of strains. The profile of patients
      colonised or infected by MRE has changed. Patients mainly infected with hospital
      acquirred MRE changed to MRE colonised patients carrying the strain into the
      hospital. The association of fluorinated quinolone resistance and Extended
      Spectrum Beta-Lactamase Enterobacteriaceae represented 51 % in 2000, became
      stable at 73 % from 2002. The association of fluorinated quinolone resistance and
      high-level Enterobacteriaceae cephalosporinase has increased from 21 % in 2000 to
      be stable at 50 % since 2006. The mesures to contain the spread of MRE strains
      remained inefficient because of outpatients circulation, multiresistant E. coli
      being community species.

PMID- 19854587
TI  - [Evaluation of cytomegalovirus quantification in blood by the R-gene real-time
      PCR test].
AB  - AIM OF THE STUDY: Diagnosing the presence of cytomegalovirus (CMV) in the blood
      of immunodepressed patients is often done by quantitative polymerase chain
      reaction (Q-PCR) even though the reference method remains the antigenemia pp65
      (Ag-pp65) test. OBJECTIVES: To define the predictive value of the Q-PCR in the
      diagnosis of CMV disease and assess treatment efficacy using the CMV R-gene test.
      To compare the Q-PCR results and feasibility with those of the Ag-pp65 test.
      PATIENTS AND METHODS: The Q-PCR was performed in 34 whole blood samples (frozen
      at -80 degrees C until use) from five patients diagnosed with CMV disease,
      defined as the presence of clinical signs and Ag-pp65 in the nuclei of more than
      two cells. After extraction, viral DNA was quantified in each sample using the Q
      PCR CMV R-gene kit according to the manufacturer's instructions. Immediately
      after blood was drawn, the Ag-pp65 test had been performed in 32 samples using
      CINAkit (Argene). RESULTS: The 16 samples positive by the Ag-pp65 test were also
      positive by PCR; six samples negative by the Ag-pp65 test were positive by PCR;
      and the remaining 10 samples were negative by both techniques. During treatment,
      the two markers' kinetics were similar. CONCLUSION: The CMV R-gene test has a
      predictive value as good as that of the Ag-pp65 test but is fast and easier to
      use. A prospective study with a greater number of patients is needed to define
      the prediction threshold for CMV disease.

PMID- 19854589
TI  - The use of spa and phage typing for characterization of a MRSA population in a
      Belgian hospital: comparison between 2002 and 2007.
AB  - TARGET OF THE STUDY: Strain typing of pathogens is essential to pinpoint the
      sources and routes of transmission and to forecast future trends. In a general
      hospital, we studied possible changes in the MRSA population. PATIENTS AND
      METHODS: MRSA isolates received from a Belgian general hospital, during 2002
      (n=150) and the second half of 2007 (n=105), were compared by phage and spa
      typing. RESULTS: In 2002, [J]* phage types characterized 45% of the MRSA
      isolates, 13% belonged to the [O]* phage types, 12% to a local phage type
      29/42E/54/D11* and 28% were not assigned to a defined group. Thirteen different
      spa types were found among the isolates: 39% belonged to t038, 27% to t121, 14%
      to t041, 5% to t740, and 4% to t002 and t024 each. Two spa types were found
      respectively in two and three isolates, five were unique. In 2007, 35% belonged
      to [J]*, 23% to [O]* and 39% could not be put in a defined group. Eighteen
      different spa types were found: 30% belonged to t740, 29% to t121, 13% to t038
      and 10% to t002. Three spa types were represented in two isolates, eleven were
      unique. The t041 spa type was specific for the 29/42E/54/D11* and the majority of
      the t121 isolates were related to [J]*. CONCLUSION: [J]* remained the dominant
      phage types group but decreased whereas [O]*, the second phage types group,
      increased. As to the spa types, t740 became dominant while t121 remained second.
      Phage and spa typing point to some quantitative changes among the Belgian MRSA
      population.

PMID- 19854590
TI  - [Pharmacokinetic evaluation of linezolid in patients with major thermal
      injuries].
AB  - The aims of this multicentre open-label study was to evaluate the
      pharmacokinetics of linezolid in patients with burn injury above 20 % BSA and to
      compare them with healthy volunteers, matched in age, sex and weight. After a
      single 600 mg IV dose of linezolid, multiple blood and urine samples were taken
      from subjects, in order to determine linezolid concentrations, using a HPLC
      assay. C(max) and volume of distribution at steady state were not different
      between the two groups. Values describing clearance were altered in burns,
      leading to a reduction by half in AUC in these patients (42.5 versus 98.1 mghL(
      1)). The enhancement of clearance was due to which of non renal clearance (323+/
      191 versus 80.4+/-27.5 mLmin(-1)). We conclude that pharmacokinetics of linezolid
      are altered in burn patients, in a magnitude sufficient that linezolid
      concentration may be subtherapeutic in some patients and we suggest that the
      dosage interval may need to be decreased in this patient population.

PMID- 19854591
TI  - A novel combination of TaqMan RT-PCR and a suspension microarray assay for the
      detection and species identification of pestiviruses.
AB  - The genus pestivirus contains four recognized species: classical swine fever
      virus, border disease virus, bovine viral diarrhoea virus types 1 and 2. All are
      economically important and globally distributed but classical swine fever is the
      most serious, concerning losses and control measures. It affects both domestic
      pigs and wild boars. Outbreaks of this disease in domestic pigs call for the most
      serious measures of disease control, including a stamping out policy in Europe.
      Since all the members of the pestivirus genus can infect swine, differential
      diagnosis using traditional methods poses some problems. Antibody tests may lack
      specificity due to cross-reactions, antigen capture ELISAs may have low
      sensitivity, and virus isolation may take several days or even longer time to
      complete. PCR-based tests overcome these problems for the most part, but in
      general lack the multiplexing capability to detect and differentiate all the
      pestiviruses simultaneously. The assay platform described here addresses all of
      these issues by combining the advantages of real-time PCR with the multiplexing
      capability of microarray technology. The platform includes a TaqMan real-time PCR
      designed for the universal detection of pestiviruses and a microarray assay that
      can use the amplicons produced in the real-time PCR to identify the specific
      pestivirus.

PMID- 19854593
TI  - The effect of short-term aerobic training on coagulation and fibrinolytic factors
      in sedentary healthy postmenopausal women.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of short-term
      aerobic training on the fibrinolytic and coagulative factors in postmenopausal
      women. STUDY DESIGN: Twenty volunteer sedentary healthy postmenopausal women (48
      53 years), who entered the menopause naturally, were divided randomly into two
      groups: training (n=10) and control (n=10). METHODS AND MAIN OUTCOME MEASURES:
      Training consisted of 10 sessions of submaximal aerobic cycling, 35 min for each
      session (5 min warm-up, 25 min aerobic training with 70% HRmax, 5 min active and
      15 min passive recovery), 3 times a week. Coagulation and fibrinolytic factors
      were assessed both before and after aerobic program in both groups. RESULTS:
      Fibrinogen, von Willbrand factor (vWF-Ag) antigen, plasminogen activator
      inhibitor-1 activity (PAI-1:Ac) and antigen (PAI-1:Ag) showed significant
      reduction after 10 sessions in the training group (P<0.05). Also after training,
      prothrombin time (PT), partial thromboplastin time (PTT), tissue plasminogen
      activator activity (tPA:Ac) and antigen (tPA:Ag) increased (P<0.05). CONCLUSION:
      It was concluded that fibrinolytic activity on postmenopausal women could be
      improved by a 3-week regular submaximal training program. These changes on the
      hemostatic factors suggest that short-term aerobic training may prevent the
      decline in fibrinolytic function observed in sedentary postmenopausal women.

PMID- 19854594
TI  - Predicting adult stature from metatarsal length in a Portuguese population.
AB  - Stature can be considered one of the "big four" parameters to be ascertained
      within the biological profile in cases of forensic anthropology. However, the
      most reliable available methods for stature estimation require the preservation
      of the long bones, but since this is very often not the case, the development of
      alternative methods, based on distinct bones, is mandatory. Therefore, in the
      present work the reliability of the first two metatarsal bones in reconstructing
      stature is tested. The data consist of length measurements taken from the first
      two metatarsals removed from documented cadavers of known stature. The sample for
      this study consists of 220 metatarsals, namely 110 first metatarsals and 110
      second metatarsals collected during the autopsies carried out in the National
      Institute of Legal Medicine in Portugal. The aim was to propose regression
      equations for the Portuguese population and test the formulae proposed by other
      authors to determine adult stature using metatarsal bones. We found that when
      estimating stature from measurement of the metatarsals, the best correlation was
      that obtained from the relationship with the maximum length of the 2nd
      metatarsal. The corresponding regression equation is as follows:
      S=790.041+11.689M2.

PMID- 19854595
TI  - Age estimation by pulp/tooth area ratio in canines: study of a Portuguese sample
      to test Cameriere's method.
AB  - Age estimation in adults is an important problem in both anthropological and
      forensic fields, and apposition of secondary dentine is often used as an
      indicator of age. In recent papers, Cameriere et al. studied the pulp/tooth area
      ratio of canines for this purpose. The present study examines the application of
      the pulp/tooth area ratio by peri-apical X-ray images as an age indicator in a
      Portuguese identified sample. The statistical model was then compared with
      results from an Italian identified sample, to establish whether a common
      regression model for both samples could be developed. The Portuguese sample
      consisted of 126 canines of male and 132 of female from subjects 20 to 84 years
      old, from the osteological collection of the Museum of Anthropology at Coimbra
      University. The Italian sample consisted of 114 canines of male and 86 of female
      from subjects 20 to 79 years old, analyzed in Cameriere et al. (2007), and came
      from the Frassetto osteological collection of Sassari (Sardinia), now housed in
      the Museum of Anthropology, Department of Experimental and Evolutionistic
      Biology, University of Bologna. Statistical analysis was performed in order to
      obtain multiple regression formulas for dental age calculation, with
      chronological age as dependent variable, and gender and pulp/tooth area ratio on
      upper (RA(u)) and lower canines (RA(l)) as independent variables. ANCOVA analysis
      showed that gender was not significant but that variables RA(u) and RA(l) were.
      The regression model for the Portuguese sample yielded the following equations:
      Age=101.3-556.68 RA(u) (upper canines) and Age=92.37-492.05 RA(l) (lower
      canines). Both models explained about 97% of total variance, and mean prediction
      errors were ME=2.37 years and 2.55 years, respectively. Comparisons between the
      equation referring to the Portuguese sample and the equivalent linear equations
      proposed by Cameriere et al. for the Italian sample did not reveal significant
      differences between the linear models, suggesting that a common regression model
      could be applied for both samples. The common regression model, describing age as
      a linear function of RA(u) and RA(l), yielded the following linear regression
      formulas: Age=100.598-544.433 RA(u); Age=91.362-480.901 RA(l), and explained 86%
      and 93% of total variance, respectively. Mean prediction errors were ME=2.68
      years and 2.73 years, respectively.

PMID- 19854596
TI  - Giant neck liposarcoma with pathological clavicular fracture.
AB  - Liposarcomas generally originate in the extremities or retroperitoneum, they are
      very unusual in the head and neck region, and extremely rare in the thorax. The
      mainstay of treatment for liposarcomas is surgical excision. We report a very
      unusual case, not reported before to our knowledge, of a well-differentiated
      liposarcoma arising from the supraclavicular fossa that produces a pathological
      clavicular fracture. The patient underwent complete resection of the lesion,
      without damage of the cervical nerves. Eight months after the surgery the patient
      is free of recurrence. We demonstrate that giant liposarcomas can be resected
      completely without morbidity.

PMID- 19854597
TI  - Spatial anatomy of the nasofrontal recess on the CT using multiplanar
      reconstruction technique.
AB  - OBJECTIVE: To clarify the spatial orientation relevant to the endoscopic sinus
      surgery (ESS) for the frontal sinus. METHODS: Various dimensions of structures
      around the frontal recess were measured on 256 CT images of 128 Japanese patients
      using the multiplanar reconstruction technique. Measurements done in this study
      were: the distance from the nostril to the narrowest point of the frontal recess
      (D1), and the distance from the narrowest point of the frontal recess to the bony
      wall of the anterior skull base on an extension of the same line (D2). The
      smallest anterior-posterior (D3) and right-left (D4) diameters of the "route to
      the frontal sinus," a site containing the narrowest airspace in the frontal
      recess, being surrounded by the posterior edge of maxillary bone anteriorly, by
      the bony wall of the anterior skull base posteriorly, by the middle turbinate
      medially, and by the medial orbital bony wall laterally, respectively, on the
      parasagittal and coronal planes. The angle between the line connecting the
      nostril to the lowest portion of the frontal process of the maxilla and frontal
      bone, and the line connecting the lowest portion of the frontal process to the
      narrowest portion of the frontal recess (A1). RESULTS: The mean values D1-D4 were
      55.9, 9.4, 6.9 and 8.2mm. In 154 of 256 sides, A1 ranged from 129.5 degrees to
      175.7 degrees. CONCLUSION: The present study provides important information about
      the spatial anatomy of the nasofrontal recess, which is essential for avoiding
      complications of an ESS for the frontal sinus.

PMID- 19854598
TI  - Maxillofacial mass as the first presentation of acute lymphoblastic leukemia in a
      nine-year-old girl.
AB  - A nine-year-old girl complained of a maxillofacial mass and mild fever lower than
      37.5 degrees C. A solid mass was detected in the right maxillary fossa by CT and
      sonographic examination, and the tumor extended backward into the infratemporal
      fossa without bony destruction. Laboratory studies showed a white blood cell
      (WBC) count of 31.6x10(9)/L, which increased progressively to 50.0x10(9)/L over
      the next several days. Peripheral blood smear revealed 92% lymphoblast with
      uneven bulk. A biopsy through the right labiogingival groove disclosed a
      submucosal homogeneous mass. Histologic examination under the microscope revealed
      atypical mononuclear cells with obvious atypia and nuclear divisions. Bone marrow
      puncture showed atypical lymphocytes with active proliferation. Immune phenotypic
      analysis by flow cytometry showed that malignant cells were positive for CD19,
      CD34, HLA-DR, CD38, CD22, CD58, CD45 and CD56. Real time RT-PCR revealed positive
      BCR/ABL arrangement. High-risk ALL was diagnosed and four stages of
      chemotherapies were given for nearly three years. After the induction of the
      chemotherapy, the facial mass disappeared. A bone marrow biopsy revealed that CR
      had been achieved since a month after chemotherapy's onset. The initial
      presentation of ALL as a maxillofacial mass is exceedingly rare. To the best of
      the authors' knowledge, this is the first reported case of ALL presenting as a
      maxillofacial lesion.

PMID- 19854599
TI  - Treatment of febrile seizures: historical perspective, current opinions, and
      potential future directions.
AB  - Although most febrile seizures do no harm and two-thirds of initial cases have no
      witnessed recurrence, the seizures cause much family anxiety, and are sometimes
      prolonged. In rare cases they are the first evidence of important epilepsy
      syndromes or are implicated in the development of epilepsy with mesial temporal
      sclerosis in later life. There have been trials of prophylactic treatment with
      antiepileptic drugs including carbamazepine, diazepam, phenobarbital, phenytoin,
      and sodium valproate. Several strategies have been employed with these drugs,
      including continuous secondary prophylaxis, intermittent secondary prophylaxis in
      response to later episodes of fever, and rescue medication early in the course of
      further seizures. Another treatment strategy has been using one or more
      antipyretic agents in early response to fever using agents such as acetaminophen
      and ibuprofen. Over the years, researchers have identified a variety of clinical,
      genetic, and environmental risk factors for more severe or prolonged febrile
      seizures and higher risk of recurrence. This review evaluates the rationale for
      secondary prophylaxis of febrile seizures, the potential effectiveness of such
      treatment, and whether it can be recommended as a general approach to treating
      febrile seizures or as an approach to be used in groups identified to be at
      increased risk.

PMID- 19854600
TI  - Dravet syndrome: early clinical manifestations and cognitive outcome in 37
      Italian patients.
AB  - Aims of our study were to describe the early clinical features of Dravet syndrome
      (SMEI) and the neurological, cognitive and behavioral outcome. The clinical
      history of 37 patients with clinical diagnosis of SMEI, associated with a point
      mutation of SCN1A gene in 84% of cases, were reviewed with particular attention
      to the symptoms of onset. All the patients received at least one formal cognitive
      and behavior evaluation. Epilepsy started at a mean age of 5.7 months; the onset
      was marked by isolated seizure in 25 infants, and by status epilepticus in 12;
      the first seizure had been triggered by fever, mostly of low degree in 22
      infants; the first EEG was normal in all cases. During the second year of life
      difficult-to-treat seizures recurred, mostly triggered by fever, hot bath, and
      intermittent lights and delay in psychomotor development became evident. At the
      last evaluation, performed at a mean age of 16+/-6.9 years, mental retardation
      was present in 33 patients, associated with behavior disorders in 21. Our data
      indicate that the most striking features of SMEI are: the early onset of seizures
      in a previously healthy child, the long duration of the first seizure, the
      presence of focal ictal symptoms, and sensitivity to low-grade fever. Diagnosis
      of SMEI may be proposed by the end of the first year of life, and a definite
      diagnosis can be established during the second year based on the peculiar seizure
      favoring factors, EEG photosensitivity and psychomotor slowing. The temporal
      correlation between high seizure frequency and cognitive impairment support the
      role of epilepsy in the clinical outcome, even if a role of channelopathy cannot
      be ruled out.

PMID- 19854601
TI  - 1H NMR-based metabonomic study on the metabolic changes in the plasma of patients
      with functional dyspepsia and the effect of acupuncture.
AB  - Functional dyspepsia (FD) is a common gastrointestinal disorder with multiple
      pathogenic mechanisms seen in clinical practice, and acupuncture may potentially
      be an alternative therapy for it. In order to investigate the biological effects
      of FD and the effect of acupuncture on metabolism, (1)H nuclear magnetic
      resonance (NMR)-based metabonomic techniques have been used to compare the plasma
      metabolic profiles of six female FD patients with those of six female healthy
      control subjects. Plasma metabolic profiles of FD patients treated by acupuncture
      at the Foot-Yangming Meridian were also collected and compared. Data obtained
      from NMR spectroscopy were subjected to principal components analysis (PCA). The
      results show that there are relatively higher levels of glucose, acetate, high
      density lipoprotein (HDL), and phosphatidylcholine (PtdCho), and lower levels of
      lactate, leucine/isoleucine, N-acetyl glycoprotein (NAc), and low-density
      lipoprotein/very low-density lipoprotein (LDL/VLDL) in FD patients than in
      healthy controls. Acupuncture treatment of FD patients significantly changed the
      levels of leucine/isoleucine, lactate and glucose, and slightly changed lipids
      level towards those of the healthy controls, demonstrating its therapeutic
      effects on the relief of FD symptoms. Due to the limited number of subjects, the
      present work is just a proof-of-principle study and further researches with
      larger number of subjects are needed. Our work shows the potential of an NMR
      based metabonomic approach in the study of biological effects of acupuncture.

PMID- 19854602
TI  - Simultaneous determination of dopamine and 3,4-dihydroxyphenylacetic acid in
      mouse striatum using mixed-mode reversed-phase and cation-exchange high
      performance liquid chromatography.
AB  - The measurement of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) is useful
      for an index of dopamine turnover. We developed a simultaneous determination
      method for dopamine and DOPAC with high-performance liquid chromatography
      fluorescence detection. Mixed-mode reversed-phase and cation-exchange column
      (CAPCELL PAK CR column) which contained C18 silica particles and sulfonic acid
      cation-exchange particles was used for the separation of 3,4-dihydroxy-l
      phenylalanine, catecholamines (norepinephrine, epinephrine, and dopamine) and
      DOPAC. The mobile phase was optimized for factors such as pH and counter ion
      concentration. With a mobile phase of 15 mM sodium acetate buffer (pH 4.5),
      separation was achieved within 22 min. The developed method was applicable to the
      determination of dopamine and DOPAC in mouse striatum. The concentrations of
      dopamine and DOPAC in mouse striatum were 4.98+/-0.66 and 1.00+/-0.11 microM,
      respectively (n=10).

PMID- 19854603
TI  - Identification of prenyl flavonoid glycosides and phenolic acids in Epimedium
      koreanum Nakai by Q-TOF-MS combined with selective enrichment on "click oligo
      (ethylene glycol)" column.
AB  - Prenyl flavonoid glycosides and phenolic acids are constituents of the medicinal
      plant Epimedium koreanum Nakai (EK). An efficient method was developed to enrich
      these compounds and identify them, using ultra performance liquid chromatography
      combined with Q-TOF-MS, and a "click oligo (ethylene glycol)" (Click OEG) column.
      Using this method, 51 prenyl flavonoid glycosides and 18 phenolic acids were
      identified or tentatively identified. Of these, 11 prenyl flavonoid glycosides
      and 4 phenolic acids were new compounds, and 7 phenolic acids were newly
      identified in EK. Therefore, MS combined with selective enrichment provided a
      powerful means for analyzing prenyl flavonoid glycosides and phenolic acids.

PMID- 19854604
TI  - The impact of a multimedia informational intervention on psychosocial adjustment
      among individuals with newly diagnosed breast or prostate cancer: a feasibility
      study.
AB  - OBJECTIVE: To examine the impact of an 8-week cancer multimedia informational
      intervention on health-related outcomes among individuals newly diagnosed with
      cancer. METHODS: Using a pre-/post-quasi-experimental design, participants with
      breast or prostate cancer (n=250) were conveniently recruited from four oncology
      ambulatory clinics and completed questionnaires at three points (enrolment, 1-2
      weeks post-intervention, and 3 months later). RESULTS: Repeated-measure analyses
      showed that, when compared to controls, the intervention significantly improved
      satisfaction with cancer information over time for women (p<.001), prevented
      deterioration in functional quality of life (p=.030) and marginally improved
      perceived oncologist informational support (p=.051). There were no significant
      differences in psychosocial adjustment among men. Unlike previously suggested,
      the intervention did not have a differential impact according to levels of
      personal resources (self-esteem, mastery, and optimism). However, for all
      outcomes and regardless of group, participants high in personal resources
      reported better adjustment across time. CONCLUSION: Even though the hypotheses
      were only partially supported, the findings provide preliminary evidence that
      multimedia interventions can be supportive. PRACTICE IMPLICATIONS: With
      increasing numbers of new cancer diagnoses, cancer survivors and more limited
      health care resources, further research is needed to evaluate potential benefits
      of health information technology in providing support to individuals facing
      cancer.

PMID- 19854606
TI  - Prognostic value of lymph node metastases and lymph node ratio in esophageal
      squamous cell carcinoma.
AB  - AIMS: Although the positive lymph node (LN) metastasis in patients with thoracic
      esophageal squamous cell carcinoma carcinoma (SCC) has been reported to be a risk
      factor to reduce long-term survival, only a few studies have so far evaluated the
      lymph node metastasis among this group of patients. The purpose of this study was
      to evaluate the impact of lymph node positivity and ratio on survival of
      esophageal SCC. METHODS: All patients undergoing esophagectomy at the Forth
      Hospital of Hebei Medical University between January 1986 and December 2002 were
      reviewed. Survival curves were estimated using the Kaplan-Meier method. RESULTS:
      Of 1,325 patients with invasive cancer, had squamous cell cancer of the
      esophagus. Median overall survival (OS) of the entire group was 36.7 months and 5
      year OS was 39.3%. The most significant prognostic factor for overall survival
      was the presence of positive LN (P<0.01). Additionally, patients with zero
      involved LN had a 5-year survival of 49.1%, while patients with 1-3 positive LN
      and >3 positive LN had 5-year survival of 19.5% and 11.0%, respectively (P<0.01).
      Finally, an increasing ratio of positive to examined LN was linearly associated
      with a worsening 5-year survival, patients with <25%, 25%-50% and >50% positive
      LN had 5-year survival of 47.53%, 14.6% and 8.9%, respectively (P<0.01).
      CONCLUSION: Increasing number of positive LN in patients with esophageal cancer
      and increasing ratio of metastatic to examine LN portend a poor prognosis. These
      factors should play an important role in predicting prognosis of patients.

PMID- 19854605
TI  - Predictors of nutrition information comprehension in adulthood.
AB  - OBJECTIVE: The goal of the present study was to examine relationships among
      several predictors of nutrition comprehension. We were particularly interested in
      exploring whether nutrition knowledge or motivation moderated the effects of
      attention on comprehension across a wide age range of adults. METHODS: Ninety
      three participants, ages 18-80, completed measures of nutrition knowledge and
      motivation and then read nutrition information (from which attention allocation
      was derived) and answered comprehension questions. RESULTS: In general, predictor
      variables were highly intercorrelated. However, knowledge, but not motivation,
      had direct effects on comprehension accuracy. In contrast, motivation influenced
      attention, which in turn influenced accuracy. Results also showed that
      comprehension accuracy decreased-and knowledge increased-with age. When knowledge
      was statistically controlled, age declines in comprehension increased.
      CONCLUSION: Knowledge is an important predictor of nutrition information
      comprehension and its role increases in later life. Motivation is also important;
      however, its effects on comprehension differ from knowledge. PRACTICE
      IMPLICATIONS: Health educators and clinicians should consider cognitive skills
      such as knowledge as well as motivation and age of patients when deciding how to
      best convey health information. The increased role of knowledge among older
      adults suggests that lifelong educational efforts may have important payoffs in
      later life.

PMID- 19854607
TI  - [Residual curarization and pharyngeal muscles: remain vigilant!].
AB  - The different concepts treating of "residual curarization" were presented
      according to two directions: the analysis of their contents--epidemiologic,
      clinical, instrumental--and the description of the pharyngeal striated muscles
      functions in these contexts. It appears that certain, too marked, "residual
      curarization" levels remain a well-evidenced factor increasing some morbidities
      in numerous clinical situations. All the methods of instrumental monitoring of
      the level of curarization--mecanography, electromyography, accelerometry-
      appeared useful to document the levels of "residual curarization" before
      patient's extubation or awakening. Today, for our speciality, it became
      particularly clear that: neither the selected muscle-- adductor pollicis--,
      neither the test currently privileged--train-of-four 2Hz--, nor the thresholds
      currently selected--0.90 or 1.00--did not constitute the unavoidable proof of a
      "residual curarization" complete absence. For the healthy volunteer receiving a
      curare, a train of four of the adductor pollicis greater than 0.90 can exist in
      presence of spirometric alterations evidencing the lack of adequate pharyngeal
      dilatation. In daily routine, the pharyngeal control is already disturbed by
      numerous molecules including: benzodiazepines, halogenated vapours, propofol,
      i.e. even under non-hypnotic concentrations. Faced to such evidences, our medical
      speciality will, undoubtedly, have to acquire new knowledge to develop muscle
      relaxant management control processes eliminating the surmorbidities related to
      "residual curarization". These tests must be validated also to exclude morbidity
      prone dysfunctions of the pharyngeal striated muscles. Considering this new
      paradigm would be a major safety evolution for our speciality.

PMID- 19854608
TI  - Cavum septi pellucidi in boxers.
AB  - OBJECTIVE: Controversy exists over the significance of the isolated finding of
      cavum septi pellucidi (CSP) and its prevalence rate in healthy individuals and in
      professional boxers. Few magnetic resonance imaging (MRI) studies have looked at
      large cohorts of boxers. The aim of this study was to identify the prevalence and
      extent of a CSP among professional boxers and to compare these with a control
      group. METHODS: MRI studies of 164 male boxers scanned for annual British boxing
      board license renewal were reviewed and compared with 43 control patients. CSP
      prevalence, size, and extent were recorded. Extent was classified as type 1,
      anterior to the fornix; type 2, extending up to the fornix; and type 3, extending
      into the cavum vergae. Parenchymal abnormalities were documented, and the Evan's
      ratio was used as an indication of brain atrophy. RESULTS: A CSP was present in
      40% of controls and 49% of boxers. There was a trend to a higher CSP prevalence
      in boxers (P = .099). No control patient had type 2 or 3 extension (P < .0009),
      as opposed to 30% and 16% prevalence in boxers. Three boxers increased their
      extent over serial imaging. No difference in CSP size was established between the
      2 groups (P = .43), but there was an association between progressive scans and
      increased CSP size over time in boxers, independent of age (P = .05). Eight
      boxers demonstrated a CSP on a subsequent scan not seen on an earlier scan.
      CONCLUSION: The prevalence of a CSP is high among both control patients and
      boxers. There is a trend to a larger CSP with increasing number of scans without
      evidence of atrophy and independent of age. Boxers also have a greater posterior
      extent than controls. The findings may be explained by sudden increases in
      intracranial pressure that forced cerebrospinal fluid (CSF) through small defects
      in the septal leaflets, which result in an increase in size and or extent of a
      CSP.

PMID- 19854609
TI  - The pursuit of impalpable thyroid nodules: are we using scarce resources wisely?

PMID- 19854610
TI  - Dabigatran etexilate prevents venous thromboembolism after total knee
      arthroplasty in Japanese patients with a safety profile comparable to placebo.
AB  - We assessed the efficacy, safety, and dose-response of dabigatran etexilate (DAB)
      in preventing venous thromboembolism (VTE) in Japanese patients undergoing total
      knee arthroplasty (TKA). Five hundred twelve patients received DAB (110, 150, or
      220 mg) or placebo once daily for 11 to 14 days, starting the day after surgery.
      The primary efficacy end point was the incidence of total VTE and all-cause
      mortality; the primary safety end point was incidence of major, clinically
      relevant, and minor bleeding events. Total VTE and all-cause mortality were lower
      in patients receiving DAB (39.6%, 32.7%, and 24.0%) than placebo (56.4%). There
      was no difference in the incidence of major bleeding between the DAB and placebo
      groups. Overall, DAB reduced the incidence of VTE in Japanese patients undergoing
      TKA, with a comparable safety profile vs placebo.

PMID- 19854611
TI  - Continuous deep sedation in medical practice: a descriptive study.
AB  - CONTEXT: Continuous deep sedation (CDS) until death can form an effective part of
      palliative care. In The Netherlands and Belgium, CDS is sometimes regarded as an
      alternative to euthanasia, and the involvement of palliative care specialists is
      low. Provision of CDS through opioids alone is not recommended. OBJECTIVES: This
      study investigates the use of CDS in the United Kingdom. METHODS: A survey of
      8,857 doctors, of whom 3,733 (42%) replied, with 2,923 reporting on their last
      patient who died. RESULTS: In total, 18.7% (17.3-20.1) of the doctors attending a
      dying patient reported the use of CDS. CDS was more likely when patients were
      younger or were dying of cancer. Specialists in care of the elderly were least
      likely to report the use of CDS; doctors in other hospital specialties were most
      likely to report its use. CDS was associated with a higher rate of requests from
      patients or relatives for a hastened death and with a greater incidence of other
      end-of-life decisions containing some intent to end life by the doctor. Doctors
      supporting legalization of euthanasia or physician-assisted suicide, or who were
      nonreligious, were more likely to report using CDS. There was palliative care
      team involvement in half of all CDS cases, and prescription of opioids alone for
      sedation occurred in one-fifth of the cases but was not reported by specialists
      in palliative care. CONCLUSION: This study provides baseline data for monitoring
      future trends in the United Kingdom and highlights the need for a fuller
      understanding of the circumstances in which CDS occurs in particular care
      settings.

PMID- 19854612
TI  - Cognitive vulnerability to anxiety in the stress generation process: interaction
      between the Looming Cognitive Style and Anxiety Sensitivity.
AB  - This study sought to extend the investigation of cognitive-personality
      vulnerability in the stress generation process to the field of anxiety. We
      examined two well documented cognitive vulnerabilities to anxiety: the Looming
      Cognitive Style (LCS) and Anxiety Sensitivity (ASI). Investigating 72
      undergraduates who were assessed twice over a 4-month interval, we found support
      for the hypothesis that the two cognitive vulnerabilities to anxiety augment each
      other's stress generating effect. Results indicated that combination of LCS and
      ASI together had a far stronger stress generation effect that would just one
      factor alone. Each factor was positively associated with Time 2 stressful events
      under high levels of the other, but not under low levels. Thus findings revealed
      that the joint combination of the two cognitive vulnerabilities seemed to play a
      particularly marked role over a 4-month time interval. These findings are
      important because they are among the first to show stress generation effects for
      anxiety-related cognitive styles.

PMID- 19854613
TI  - Extraction of dynamic features from hand drawn data for the identification of
      children with handwriting difficulty.
AB  - Studies have shown that differences between children with and without handwriting
      difficulties lie not only in the written product (static data) but also in
      dynamic data of handwriting process. Since writing system varies among countries
      and individuals, this study was conducted to determine the feasibility of using
      quantitative outcome measures of children's drawing to identify children who are
      at risk of handwriting difficulties. A sample of 143 first graders of a normal
      primary school was investigated regarding their handwriting ability. The children
      were divided into two groups: test and control. Ten children from test group and
      40 children from control group were individually tested for their Visual Motor
      Integration skills. Analysis on dynamic data indicated significant differences
      between the two groups in temporal and spatial measures of the drawing task
      performance. Thus, kinematic analysis of children's drawing is feasible to
      provide performance characteristic of handwriting ability, supporting its use in
      screening for handwriting difficulty.

PMID- 19854615
TI  - Calretinin immunoreactivity in focal cortical dysplasias and in non-malformed
      epileptic cortex.
AB  - Focal cortical dysplasias (FCDs) represent a prominent cause of pharmacologically
      intractable epilepsy. In FCD, the decrease of parvalbumin immunoreactive (PV+)
      inhibitory interneurons has been repeatedly documented. Here, we wanted to show
      whether another interneuronal population, the calretinin immunoreactive (CR+)
      neurons, exhibits any change in human FCD. We also investigated samples of
      morphologically normal temporal neocortex resected together with sclerotic
      hippocampus (nHSTN), where decrease of PV+ interneurons was previously documented
      as well. Brain tissue from 24 patients surgically treated for pharmacoresistant
      epilepsy was examined. Calretinin immunoreactivity was qualitatively evaluated
      and the density of CR+ neuronal profiles was quantified. As a control, post
      mortem acquired neocortical samples of nine patients without any brain affecting
      disease were used. CR+ neurons were located predominantly in superficial cortical
      layers both in controls and pathological samples. Similarly, the morphology of
      CR+ neurons was unaffected in pathological samples. The overall density of CR+
      neurons was significantly decreased in FCD type I (to approximately 70% of
      control values) and even more in FCD type II (to approximately 50% of controls).
      In nHSTN, no change compared to controls was found in CR+ neuronal density. Our
      results may contribute to the better understanding of the role of individual
      interneuronal populations in epileptogenesis.

PMID- 19854614
TI  - Complications of sevoflurane-fentanyl versus midazolam-fentanyl anesthesia in
      pediatric cleft lip and palate surgery: a randomized comparison study.
AB  - Careful choice of anesthetic agents in pediatric patients reduces the frequency
      of anesthesia-related complications. The frequency and type of intraoperative and
      postoperative complications of sevoflurane-fentanyl versus midazolam-fentanyl
      anesthesia were compared in 140 consecutive children (aged 3 months to 10 years)
      undergoing cleft lip and palate repair. Midazolam-fentanyl anesthesia was induced
      with midazolam (0.05 mg/kg), fentanyl (0.005 mg/kg) and vecuronium (0.1mg/kg),
      and maintained with the same agents according to the defined parametars.
      Sevoflurane-fentanyl anesthesia was induced and maintained with sevoflurane (5-8
      vol% and 0.8-1 vol%, respectively) in an oxygen/air mixture and supplemented with
      fentanyl (0.005 mg/kg). Both groups were comparable in basic demographic data,
      hemodynamic and respiratory parameters. Difficult intubation occurred in 6 of 76
      children (midazolam-fentanyl group) and 4 of 64 children (sevoflurane-fentanyl
      group) (P=0.754). Ventricular extrasystole and bronchospasm occurred in one
      patient each in the sevoflurane-fentanyl group. Postoperatively, emergence
      agitation was observed in the sevoflurane-fentanyl group (17 cases; P<0.001);
      postoperative nausea and vomiting occurred in 2 children (midazolam-fentanyl
      group) and 3 children (sevoflurane-fentanyl group) (P=0.660). Midazolam-based
      anesthesia in children is safer than sevoflurane-based anesthesia regarding
      occurrence of emergence agitation.

PMID- 19854616
TI  - Blood pressure changes after intravenous fosphenytoin and levetiracetam in
      patients with acute cerebral symptoms.
AB  - PURPOSE: To study the incidence and extent of the occasionally noted hypotension
      after intravenous (IV) infusions of fosphenytoin (FOS) and levetiracetam (LEV) in
      patients presenting with acute cerebral symptoms. METHODS: Retrospective data
      collection of consecutive patients with acute cerebral symptoms who received IV
      infusions of a single dose of 750 mg or more of either fosphenytoin or
      levetiracetam and had documented blood pressure values in the 2h prior and the 2h
      after their IV infusion. RESULTS: More than 10 mmHg drop in the systolic,
      diastolic and MBP was observed in the FOS group following the IV infusion (-16.82
      mmHg, -11.60 mmHg, and 13.34 mmHg, respectively). However, there was not a
      significant change in the MBP after LEV infusion (1.54 mmHg, 1.84 mmHg, and 1.74
      mmHg for systolic, diastolic and MBP change, respectively). The difference in the
      systolic, diastolic and MBP changes between the two groups was statistical
      significant (all p values are <0.0001) after adjusting for age, clinical
      presentations of the patients and if they were on any antihypertensive medication
      in the hospital. Sixty two percent of patients who received FOS had >10 mmHg
      decrease in their MBP. In the LEV group, only 2 of the 50 patients (4%) had >10
      mmHg decrease in their MBP. The difference in proportion of the patients with >10
      mmHg drop in MBP between the two study groups is also statistically significant
      (p<0.001) for age, clinical presentations of the patients and if they were on any
      antihypertensive medication in the hospital. CONCLUSIONS: IV infusion of FOS in
      subjects presenting with acute cerebral symptoms may cause significant decreases
      in their blood pressure. This was not seen in patients receiving IV LEV
      infusions. Since maintaining adequate cerebral perfusion pressure is a key point
      in the management of patients with acute cerebral symptoms, the results of this
      study may carry a clinical impact on the management of this subgroup of patients.

PMID- 19854617
TI  - Neurodevelopmental effects of anti-epileptic drugs.
AB  - Use of medication with a desired effect on the central nervous system (as with
      anti-epileptic drugs) in children will undoubtedly cause concern about
      neurodevelopment. Data are emerging to suggest an effect of anticonvulsants on
      the developing brain of the unborn child when administered to mothers with
      epilepsy. This obviously requires detailed evaluation, especially when
      considering the risks of epilepsy itself. In the child with epilepsy, many of the
      early onset epilepsies are associated with developmental compromise as part of
      their clinical profile, and therefore determining the relative effects of the
      underlying cause, seizures and medication can be difficult. Although data are
      available with regard to some anti-epileptic drugs (AEDs) they remain lacking
      particularly in the very young with regard to efficacy as well as
      neurodevelopmental effects of the newer anti-epileptic drugs. Ongoing evaluation
      is required to ensure the best clinical practice in each individual.

PMID- 19854618
TI  - Gray and white matter volumetric and diffusion tensor imaging (DTI) analyses in
      the early stage of first-episode schizophrenia.
AB  - PURPOSE: To determine whether statistical analyses of quantitative MR imaging
      data, including morphological changes, mean diffusivity (MD), and fractional
      anisotropy (FA), could provide useful biomarkers in early stage of first-episode
      schizophrenia. MATERIALS AND METHODS: Twenty-three patients, who met all the
      criteria in the DSM-IV-TR category for schizophrenia excluding the duration of
      the disease (less than 6 months of follow-up), were examined by MR imaging during
      the initial consultation. Nineteen of the 23 patients were finally diagnosed to
      have schizophrenia after a 6-month follow-up, and they were included in this
      study as having been in the early stage of first-episode schizophrenia. Nineteen
      healthy volunteers also underwent MR imaging as age-matched controls. Three
      dimensional spoiled gradient recalled acquisition with steady state (3D-SPGR) and
      diffusion tensor imaging (DTI) were performed at 3T. Image processing for voxel
      based morphometry, a fully automatic technique for a computational analysis of
      differences in regional brain volume throughout the entire brain, was conducted
      using the Statistical Parametric Mapping 5 software package (SPM5). The 3D-SPGR
      images in the native space were bias-corrected; spatially normalized; segmented
      into gray matter, white matter, and cerebrospinal fluid images; and intensity
      modulated using SPM5. A voxel-based analysis was conducted using both the MD and
      FA maps computed from DTI. The customized MD and FA template specific to this
      study was created from all participants. Thereafter, all the MD and FA maps in
      the native space were transformed onto the stereotactic space by registering each
      of the images to the customized MD and FA template. The two groups were compared
      using SPM5. Age and sex were treated as confounding covariates. RESULTS: The
      patients demonstrated a significant increase in the MD of the left
      parahippocampal gyrus, left insula, and right anterior cingulate gyrus in
      comparison to the control subjects (FDR corrected p<0.05). No significant
      difference was observed in the correlation between the gray/white matter volume
      and FA. CONCLUSION: These findings suggest that structural abnormalities in the
      brain are present during the early stage of first-episode schizophrenia and MD
      might therefore be a sensitive marker for the detection of these abnormalities.

PMID- 19854619
TI  - White matter correlates of clinical function in schizophrenia using diffusion
      tensor imaging.

PMID- 19854620
TI  - Treatment of co-morbid cocaine dependence in schizophrenia with topiramate.

PMID- 19854621
TI  - High remission rates from an initial ultra-high risk state for psychosis.
AB  - OBJECTIVE: To investigate the proportion of patients among subjects initially
      identified as fulfilling the ultra-high risk (UHR) criteria for psychosis using
      the Scale of Prodromal Symptoms (SOPS) who fully remitted after one year. METHOD:
      Seventy-two patients between 14 and 40 years who were referred to the Bruderholz
      Early Psychosis Outpatient Service in Switzerland and who met UHR criteria were
      included in the present study. At 1-year follow-up, data for 52 patients were
      available. Patients with transition to psychosis and patients with sustained UHR
      criteria were defined as 'cases', and patients with remission from UHR criteria
      as 'non-cases'. We compared clinical and socio-demographic characteristics
      between these two patient groups at baseline. RESULTS: 13.5% of the patients
      converted to full-blown psychosis within one year, one quarter displayed
      sustained UHR criteria, and 59.2% of the patients fully remitted from the initial
      UHR status. Outcome was independent of medication or treatment status. 'Cases'
      and 'non-cases' did not differ significantly on socio-demographic and clinical
      variables at baseline. CONCLUSIONS: The chance of remission to a non-risk state
      was over fourfold higher than the chance of conversion to psychosis within a year
      of establishing UHR status. Our data underline that the commonly used symptoms to
      identify UHR patients are often transitory and may not capture the stable core of
      developing psychosis. This highlights the danger of provoking anxiety and
      stigmatization in mislabeled individuals and missing true at-risk patients who
      present features of the psychosis core, but who do not yet-or maybe never will
      manifest positive symptoms.

PMID- 19854622
TI  - Executive function in schizophrenia: influence of substance use disorder history.
AB  - Cognitive function in schizophrenia has been associated with different
      sociodemographic and clinical variables. Substance use disorder (SUD) history has
      also been associated with cognition in schizophrenia; however, contradictory
      results have been found regarding its influence on cognitive function. Our aim
      was to study the relationship between executive function and a) age, b) duration
      of illness, c) number of psychotic episodes, d) positive symptoms, and e)
      negative symptoms, in a sample of schizophrenic patients, and secondly to study
      whether these relationships persisted after stratification of the sample
      according to the presence or absence of SUD history. A final sample of 203
      schizophrenic patients were evaluated for psychotic symptoms using the PANSS, and
      assessed using a neuropsychological battery to calculate a composite executive
      function score. Linear regression analyses were performed, with this executive
      score as the dependent variable, and age, duration of illness, number of
      psychotic episodes, positive PANSS score and negative PANSS score as independent
      variables. For the total sample, the regression model showed three variables to
      be significant predictors of the executive score: age (p=0.004), number of
      episodes (p=0.027), and PANSS negative score (p=0.003). However, once the sample
      was stratified, the regression model showed age (p=0.011) and number of episodes
      (p=0.011) to be predictor variables for the executive score in the group of
      schizophrenic patients with SUD history, while age (p=0.028) and PANSS negative
      score (p=0.006) were predictors in the group of schizophrenic patients without
      such history. These findings highlight the importance of considering SUD history
      in studies of cognitive function in schizophrenia.

PMID- 19854623
TI  - Novel keratin 14 hotspot mutation in Dowling-Meara type of epidermolysis bullosa
      simplex: strategy to avoid KRT14 pseudogene amplification by a simple approach.

PMID- 19854624
TI  - Differential gene expression in a rat model of depression based on persistent
      differences in exploratory activity.
AB  - Affective disorders are often accompanied by changes in motivation and anxiety.
      We investigated the genome-wide gene expression patterns in an animal model of
      depression that separates Wistar rats belonging into clusters of persistently
      high anxiety/low motivation to explore and low anxiety/high motivation to explore
      (low explorers and high explorers, LE and HE, respectively), in three brain
      regions previously implicated in mood disorders (raphe, hippocampus and the
      frontal cortex). Several serotonin-, GABA-, and glutamatergic genes were
      differentially expressed in LE- and HE-rats. The analysis of Gene Ontology
      biological process terms associated with the differentially regulated genes
      identified a significant overrepresentation of genes involved in the neuron
      development, morphogenesis, and differentiation; the most enriched pathways from
      the Kyoto Encyclopedia of Genes and Genomes were the Wnt signalling, MAPK
      signalling, long-term potentiation, and long-term depression pathways. These
      findings corroborate some expression data from other models of depression, and
      suggest additional targets.

PMID- 19854625
TI  - Neuropeptide Y (NPY) gene: Impact on emotional processing and treatment response
      in anxious depression.
AB  - Neuropeptide Y (NPY) has been found to play a role in the pathomechanism of both
      anxiety and depression. Thus, NPY is a promising candidate in the investigation
      of the clinical phenotype of "anxious depression". Five NPY gene variants were
      investigated for an influence on antidepressant treatment response in a sample of
      256 patients with depression. Additionally, NPY gene impact on amygdala
      activation during facial emotion processing was analyzed in a subsample of 35
      depressed patients. Particularly in anxious depression, the less active NPY
      rs16147 -399C allele conferred slow response after 2weeks and failure to achieve
      remission after four weeks of treatment. The rs16147 C allele was further
      associated with stronger bilateral amygdala activation in response to threatening
      faces in an allele-dose fashion. The present results point towards a possible
      influence of functional NPY gene variation on antidepressant treatment response
      in anxious depression, potentially conveyed by altered emotional processing.

PMID- 19854626
TI  - Formation and cross-linking of fibrinogen layers monitored with in situ
      spectroscopic ellipsometry.
AB  - Thick matrices of fibrinogen with incorporation of a matrix metalloproteinase
      inhibitor were covalently bonded on functionalized silicon surfaces using an
      ethyl-3-dimethyl-aminopropyl-carbodiimide and N-hydroxy-succinimide affinity
      ligand coupling chemistry. The growth of the structure was followed in situ using
      dynamic ellipsometry and characterized at steady-state with spectroscopic
      ellipsometry. The growth was compared with earlier work on ex situ growth of
      fibrinogen layers studied by single wavelength ellipsometry. It is found that in
      situ growth and ex situ growth yield different structural properties of the
      formed protein matrix. Fibrinogen matrices with thicknesses up to 58 nm and
      surface mass densities of 1.6 microg/cm2 have been produced.

PMID- 19854627
TI  - Toluidine blue: aggregation properties and distribution behavior in surfactin
      micelle solution.
AB  - Aggregation properties and distribution behavior of toluidine blue in surfactin
      solution have been investigated by UV, infrared spectrum and fluorescence
      measurements. The UV measurement indicates that the location of toluidine blue
      can facilitate the formation of toluidine blue aggregates in contrast to that in
      the absence of surfactin. The fluorescence results show that the micropolarity of
      pyrene initially increases and then decreases with the addition of toluidine blue
      molecules. The binding constants of toluidine blue with surfactin micelles and
      the distribution coefficients between the micelles phase and the aqueous phase
      have been calculated by Benesi-Hildebrand method and pseudo-phase model,
      respectively. The values of DeltaH degrees < 0 (-22.11 kJ/mol) and DeltaS degrees
      > 0 (12.58+/-0.07 J/(mol K)) show that electrostatic attractive interaction plays
      an important role in the location of toluidine blue in surfactin micelles.

PMID- 19854628
TI  - Cranial and postcranial skeletal variations induced in mouse embryos by mobile
      phone radiation.
AB  - This study focuses on foetal development following mild daily exposure of
      pregnant mice to near field electromagnetic radiation emitted by a mobile phone.
      The investigation was motivated by the fact that the potentially hazardous
      electromagnetic radiation emitted by mobile phones is currently of tremendous
      public interest. Physically comparable pregnant mice were exposed to
      radiofrequency radiation GSM 900MHz emitted by a mobile phone. Within 5h after
      birth most cubs were fixed followed by double staining in toto, and conventional
      paraffin histology. Other cubs remained with their mothers until teeth eruption.
      Structural development was assessed by examining newborns for the presence of
      anomalies and/or variations in soft tissues and skeletal anatomy. Electromagnetic
      radiofrequency exposed newborns, externally examined, displayed a normal
      phenotype. Histochemical and histological studies, however, revealed variations
      in the exposed foetuses with respect to control ones concerning the ossification
      of cranial bones and thoracic cage ribs, as well as displacement of Meckelian
      cartilage. Littermates examined after teeth eruption displayed normal phenotypes.
      It is concluded that mild exposure to mobile phone radiation may affect, although
      transiently, mouse foetal development at the ossification level. The
      developmental variations observed could be explained by considering the different
      embryonic origin and mode of ossification of the affected skeletal elements.

PMID- 19854629
TI  - [Vaccination rate of premature infants at 6 and 24 months of age: a pilot study].
AB  - There are few data examining the vaccine practices for 0- to 24-month-old
      premature infants born before 33 GW. The aim of the study was to examine the
      vaccine coverage in this population according to the French schedule at 6 and 24
      months. RESULTS: Eighty-seven infants were included in this regional prospective
      study. The immunization program began late and was initialized principally with
      DTPCoqHib (63%), usually after the 4th month. Fewer than one infant out of two
      (45%) had received three doses by 6 months of age. At 2 years of age, the
      coverage was 99% at 3 doses and decreased to 83% for 4 doses. For the MMR
      vaccine, the average age of administration was after 15 months, and 95% of
      infants had received one dose of MMR at 2 years of age. BCG coverage at 2 years
      of age was 94%, administered on average at 7 months. Forty-seven percent of the
      infants had received at least one dose of hepatitis B vaccine before 2 years of
      age, but only 31% had received two doses and a booster at 2 years of age. The
      adaptation of vaccination practices basically concerns the initial date of
      vaccination, but the immunization calendar is not recovered at 2 years of age.
      This should be taken into account for pertussis disease prevention in these young
      infants during the first 6 months of life, increasing the susceptibility period
      for this infectious disease. DISCUSSION AND CONCLUSION: The vaccine practices do
      not follow the postnatal chronological age of the premature baby according to the
      schedule recommended for full-term infants and vaccination is begun late. Based
      on the CSHPF vaccination recommendations, nearly 7 premature infants out of 10
      have an incomplete immunization status for DTPCoqHib, hepatitis B, and ROR at 2
      years of age. According to the pertussis coverage observed in premature infants,
      the new recommendations on vaccination of the newborn's care giver and family
      should be completed before the infant's discharge from the hospital using a new
      acellular vaccine for adult immunization. The initiation of an immunization
      program during hospitalization would be beneficial for premature babies still
      hospitalized after 2 months of age.

PMID- 19854630
TI  - [Value of continuous glucose monitoring in screening for diabetes in cystic
      fibrosis].
AB  - AIMS: In the past few years, survival has increased for people with cystic
      fibrosis (CF). Diabetes is an important complication of CF caused by pancreatic
      insufficiency, which reduces insulin secretion. Because of increased longevity of
      patients with CF, the prevalence of CF-related diabetes (CFRD) has increased.
      CFRD is associated with increased mortality and morbidity. Several studies have
      reported a decline in nutritional and pulmonary status 2-4 years before the
      diagnosis of CFRD. The introduction of insulin treatment can produce clinical
      improvement in weight and lung function. The oral glucose tolerance test is
      currently the reference method in screening for CFRD, but the current definition
      of diabetes based on the 2-h post-load plasma glucose level may not be the most
      accurate method for early detection of glucose tolerance abnormalities in CF. The
      continuous glucose monitoring system (CGMS) has been described as a useful tool
      for early detection of hyperglycemia in the CF patient. We tested the CGMS in CF
      patients with unexplained alteration of their general status. The aim of this
      study was to assess the value of the CGMS in this population. METHODS: An annual
      OGTT (following World Health Organization recommendations) was conducted as a
      screening test to identify CFRD in patients aged over 10 years or patients aged
      under 10 years with a poorer clinical status. The CGMS was performed in patients
      with unexplained worsened clinical status and without diabetes in OGTT. RESULTS:
      Forty-two patients aged from 8.5 to 19 years were screened using OGTT for CFRD.
      According to ADA criteria, 23 patients (54.8%) displayed normal glucose
      tolerance, 14 (33.3%) impaired glucose tolerance, and 5 diabetes (11.9%). Out of
      37 nondiabetic, the CGMS was used in 20 patients with unexplained altered general
      status. The CGMS revealed peaks of glucose values greater than 2 g/L in 16
      patients, 9 patients with normal glucose tolerance, and 7 patients with impaired
      glucose tolerance. The mean CGMS glucose and time of glycemic monitoring above
      1.4 g/L increased in patients with peaks greater than 2 g/L compared to patients
      without peaks (p=0.0016 and p=0.0069 respectively). After analysis of the CGMS,
      the prevalence of diabetes increased from 11.9 to 50%. Three patients aged less
      than 10 years with a normal OGTT profile presented glycemic peaks greater than 2
      g/L during CGMS. CONCLUSION: CGMS revealed more glucose metabolism abnormalities
      than OGTT in patients with unexplained altered general status.

PMID- 19854632
TI  - A daily SMS reminder increases adherence to asthma treatment: a three-month
      follow-up study.
AB  - BACKGROUND: Poor adherence to asthma treatment is a well-recognised challenge and
      is associated with increased morbidity, mortality and consumption of health care
      resources. This study examined the impact of receiving a daily text message
      reminder on one's cell phone on adherence to asthma treatment. METHODS: A total
      of 26 subjects aged 18-45 years, with a clinical history of asthma and a positive
      methacholine challenge test (PD(20)<or=4micromol) were randomised to receive, or
      to not receive, a daily short message service (SMS) reminder on their cell phone
      to take their anti-asthmatic medication. Inhaled corticosteroids to last for
      eight weeks and a prescription for four additional weeks were given to the
      subjects. The primary outcome was adherence to asthma treatment. Secondary
      outcomes were reimbursement of asthma medication, and change in exhaled nitric
      oxide levels, lung function, and airway responsiveness. RESULTS: The absolute
      difference in mean adherence rate between the two groups after 12 weeks was
      17.8%, 95% CI (3.2-32.3%), p=0.019. No significant differences were observed
      between the two randomisation groups for the secondary outcomes. CONCLUSION:
      Daily text message reminders are already after a short period of observation
      associated with increased adherence to anti-asthmatic medication.

PMID- 19854633
TI  - Determination of MBT-waste reactivity - An infrared spectroscopic and
      multivariate statistical approach to identify and avoid failures of biological
      tests.
AB  - The Austrian Landfill Ordinance provides limit values regarding the reactivity
      for the disposal of mechanically biologically treated (MBT) waste before
      landfilling. The potential reactivity determined by biological tests according to
      the Austrian Standards (OENORM S 2027 1-2) can be underestimated if the microbial
      community is affected by environmental conditions. New analytical tools have been
      developed as an alternative to error-prone and time-consuming biological tests.
      Fourier Transform Infrared (FT-IR) spectroscopy in association with Partial Least
      Squares Regression (PLS-R) was used to predict the reactivity parameters
      respiration activity (RA(4)) and gas generation sum (GS(21)) as well as to detect
      errors resulting from inhibiting effects on biological tests. For this purpose
      250 MBT-waste samples from different Austrian MBT-plants were investigated using
      FT-IR spectroscopy in the mid (MIR) and near infrared (NIR) area and biological
      tests. Spectroscopic results were compared with those from biological tests.
      Arising problems caused by interferences of RA(4) and GS(21) are discussed. It is
      shown that FT-IR spectroscopy predicts RA(4) and GS(21) reliably to assess
      stability of MBT-waste materials and to detect errors.

PMID- 19854631
TI  - Regulatory T cells and inhibitory cytokines in autoimmunity.
AB  - Foxp3(+) regulatory T cells (T(regs)) contribute significantly to the maintenance
      of peripheral tolerance, but they ultimately fail in autoimmune diseases. The
      events that lead to T(reg) failure in controlling autoreactive effector T cells
      (T(effs)) during autoimmunity are not completely understood. In this review, we
      discuss possible mechanisms for this subversion as they relate to type 1 diabetes
      (T1D) and multiple sclerosis (MS). Recent studies emphasize firstly, the role of
      inflammatory cytokines, such as IL-6, in inhibiting or subverting T(reg)
      function; secondly, the issue of T(reg) plasticity; thirdly, the possible
      resistance of autoimmune T cells to T(reg)-mediated control; and fourthly, T(reg)
      associated inhibitory cytokines TGFbeta, IL-10 and IL-35 in facilitating T(reg)
      suppressive activity and promoting T(reg) generation. These recent advances place
      a large emphasis on the local tissue specific inflammatory environment as it
      relates to T(reg) function and disease development.

PMID- 19854634
TI  - Cross-cultural comparison of concrete recycling decision-making and
      implementation in construction industry.
AB  - Waste management is pressing very hard with alarming signals in construction
      industry. Concrete waste constituents major proportions of construction and
      demolition waste of 81% in Australia. To minimize concrete waste generated from
      construction activities, recycling concrete waste is one of the best methods to
      conserve the environment. This paper investigates concrete recycling
      implementation in construction. Japan is a leading country in recycling concrete
      waste, which has been implementing 98% recycling and using it for structural
      concrete applications. Hong Kong is developing concrete recycling programs for
      high-grade applications. Australia is making relatively slow progress in
      implementing concrete recycling in construction. Therefore, empirical studies in
      Australia, Hong Kong, and Japan were selected in this paper. A questionnaire
      survey and structured interviews were conducted. Power spectrum was used for
      analysis. It was found that "increasing overall business competitiveness and
      strategic business opportunities" was considered as the major benefit for
      concrete recycling from Hong Kong and Japanese respondents, while "rising
      concrete recycling awareness such as selecting suitable resources, techniques and
      training and compliance with regulations" was considered as the major benefit
      from Australian respondents. However, "lack of clients' support", "increase in
      management cost" and "increase in documentation workload, such as working
      documents, procedures and tools" were the major difficulties encountered from
      Australian, Hong Kong, and Japanese respondents, respectively. To improve the
      existing implementation, "inclusion of concrete recycling evaluation in tender
      appraisal" and "defining clear legal evaluation of concrete recycling" were major
      recommendations for Australian and Hong Kong, and Japanese respondents,
      respectively.

PMID- 19854635
TI  - A label-free immunosensor for diagnosis of Dengue infection with simple
      electrical measurements.
AB  - The interdigitated electrodes and electrical measurements for the diagnosis of
      dengue infection using antigen-antibody conjugation method are reported. As a
      proof of concept, pre-inactivated dengue virus was firstly immobilized indirectly
      onto the immunosensor surface, pre-coated with sol-gel derived barium strontium
      titanate (BST) thin film and modified with organic self-assembled monolayer (SAM)
      formed by 3-aminopropyltriethoxysilane (APTS) and a cross-linker glutaraldehyde
      over the interdigitated electrodes. The modified sensor surface served as
      selective sensing probe to capture/conjugate the dengue antibody molecules
      present in patient's serum. Our immunosensor is based on non-faradaic process,
      using only de-ionized water as electrolyte during the simple electrical
      measurements. Both ac impedance spectroscopy and dc I-V measurements between the
      electrodes gave a clearly discernable and repeatable signal to positively
      identify the presence of dengue antibody in the serum. Direct correlation was
      obtained between the signal outputs with respect to antibody concentrations. The
      measured signal changes in impedance/current without/with the presence of dengue
      antibody were attributed to the surface conductivity change upon biomolecules
      immobilization and the dipole-induced interfacial polarization potential at the
      SAM film/biomolecules interface. By monitoring the impedance or current change,
      the antibody molecules in the patient's serum could be positively detected.

PMID- 19854636
TI  - Finding distal regulatory elements in the human genome.
AB  - Transcriptional regulation of human genes depends not only on promoters and
      nearby cis-regulatory elements, but also on distal regulatory elements such as
      enhancers, insulators, locus control regions, and silencing elements, which are
      often located far away from the genes they control. Our knowledge of human distal
      regulatory elements is very limited, but the last several years have seen rapid
      progress in the development of strategies to identify these long-range regulatory
      sequences throughout the human genome. Here, we review these advances, focusing
      on two important classes of distal regulatory sequences-enhancers and insulators.

PMID- 19854637
TI  - Testing additivity of anticancer agents in pre-clinical studies: a PK/PD
      modelling approach.
AB  - In clinical oncology, combination regimens may result in a synergistic, additive
      or antagonistic interaction (i.e. the effect of the combination is greater,
      similar or smaller than the sum of the effects of the individual compounds). For
      this reason, during the drug development process, in vivo pre-clinical studies
      are performed to assess the interaction of anticancer agents given in
      combination. Starting from a widely used single compound PK/PD model, a new
      additivity model able to predict the tumour growth inhibition in xenografted mice
      after the administration of compounds in combination was developed, under the
      assumption of a pharmacodynamic null interaction. By comparing the predicted
      curves with actual tumour weight data, possible departures from additivity can be
      immediately ascertained by visual inspection; a statistical procedure based on a
      chi(2) test has also been developed for this aim. The advantages of the proposed
      approach in comparison to other modelling methodologies are discussed and its
      application to four combination studies is presented.

PMID- 19854638
TI  - Terminalia belerica Roxb. seed oil: a potential biodiesel resource.
AB  - Terminalia belerica seeds, collected from Indian forests, were explored as an
      alternate bioresource for biodiesel synthesis. The oil yield of T. belerica seed
      is about 31% (dry weight basis). The fatty acid profile of T. belerica seed oil
      shows predominance of oleic acid (C(18:1)) glycerides (61.5%) along with linoleic
      (18.5%) and palmitic (11.6%) glycerides. Oil was extracted and evaluated for
      physico-chemical properties vis-a-vis jatropha, sunflower, soybean and rapeseed
      oil. T. belerica oil was transesterified with methanol in the presence of sodium
      methoxide catalyst. The physico-chemical properties of synthesized methyl ester
      were compared to jatropha, sunflower, soybean and rapeseed methyl esters as per
      ASTM D-6751 specification of biodiesel. Synthesized T. belerica methyl ester was
      also blended in diesel at 5-20% ratios and evaluated for key physico-chemical
      properties as per IS 1460 specification and found to meet in properties evaluated
      as per specific standards. The study revealed the possibility of T. belerica seed
      oil as potential resource of biodiesel.

PMID- 19854639
TI  - Microbial fuel cells operating on mixed fatty acids.
AB  - Strategies are being developed to harvest the energy content of the wasted sludge
      generated from the treatment of domestic wastewater. Sludge can be hydrolysed and
      fermented, giving a mixture of volatile fatty acids (VFAs). Based on the
      composition of such a fermented stream, synthetic media were created and tested
      for VFA conversion in microbial fuel cells (MFCs). Mainly acetate and propionate
      were preferred as electron donors in the mixed VFA system, which generated a
      power density of 49+/-1 mW L(NAC)(-1). The other VFAs
      (butyrates/valerates/caproic acid) were also removed, albeit at lower rates. In
      single VFA tests, each VFA could be removed, but particularly i-butyrate did not
      provide significant current generation. PCR-DGGE indicated that the microbial
      community structure was highly determined by the fed VFA, rather than by the
      initial inoculum. The communities were dominated by Proteobacteria such as
      Geobacter, Comamonas, Pseudomonas and Pelobacter species. This study demonstrated
      the feasibility of using fatty acids, as present in fermented sludge
      hydrolysates, for current generation.

PMID- 19854640
TI  - Removal of nitrate from aqueous solutions by activated carbon prepared from sugar
      beet bagasse.
AB  - In this study, activated carbons were prepared from sugar beet bagasse by
      chemical activation and the prepared activated carbons were used to remove
      nitrate from aqueous solutions. In chemical activation, ZnCl(2) was used as
      chemical agent. The effects of impregnation ratio and activation temperature were
      investigated. The produced activated carbons were characterized by measuring
      their porosities and pore size distributions. The microstructure of the activated
      carbons was examined by scanning electron microscopy (SEM). The maximum specific
      surface area of the activated carbon was about 1826m(2)/g at 700 degrees C and at
      an impregnation ratio of 3:1. The resulting activated carbon was used for removal
      of nitrate from aqueous solution. The effects of pH, temperature and contact time
      were investigated. Isotherm studies were carried out and the data were analyzed
      by Langmuir, Freundlich and Temkin equations. Three simplified kinetic models
      were tested to investigate the adsorption mechanism.

PMID- 19854641
TI  - Biosorption of cadmium by endophytic fungus (EF) Microsphaeropsis sp. LSE10
      isolated from cadmium hyperaccumulator Solanum nigrum L.
AB  - A novel technology to obtain highly efficient biosorbent from the endophytes of a
      hyperaccumulator is reported. This technology is more convenient than the
      traditional method of obtaining biosorbents by experimentally screening many
      types of biomass by trial and error. Using this technology, endophytic fungus
      (EF) LSE10 was isolated from the cadmium hyperaccumulator Solanum nigrum L. It
      was identified as Microsphaeropsis sp. When cultured in vitro, the biomass yield
      of this EF was more than twice that of none-endophytic fungus (NEF) Rhizopus
      cohnii. Subsequently, it was used as a biosorbent for biosorption of cadmium from
      the aqueous solution. The results showed that the maximum biosorption capacity
      was 247.5mg/g (2.2 mmol/g) which was much higher than those of other adsorbents,
      including biosorbents and activated carbon. Carboxyl, amino, sulphonate and
      hydroxyl groups on EF LSE10 surface were responsible for the biosorption of
      cadmium.

PMID- 19854642
TI  - Preparation and characterization of phenol-formaldehyde adhesives modified with
      enzymatic hydrolysis lignin.
AB  - Phenol-formaldehyde (PF) adhesives modified with enzymatic hydrolysis lignin
      (EHL) were synthesized by a one-step process. The phenol component of the PF
      adhesives was partially substituted by EHL extracted from the residues of
      cornstalks used to produce bio-ethanol. The EHL-PF adhesives were used to prepare
      plywoods by hot-pressing. The pH value, viscosity, solid content, free phenol
      content, free formaldehyde content and brominable substance content of EHL-PF
      resins were investigated. The bonding strengths of the plywoods were determined,
      and the influences of the replacement percentage of phenol by EHL (a) and the
      NaOH content (b) on the properties of the adhesives were investigated. The
      results showed that the performance of the modified adhesives and the plywoods
      glued with them almost met the Chinese National Standard (GB/T 14732-2006) for
      first grade plywood when 20 wt% of the phenol was replaced by EHL.

PMID- 19854643
TI  - Design and synthesis of novel histone deacetylase inhibitor derived from nuclear
      localization signal peptide.
AB  - We describe herein the synthesis and characterization of a new class of histone
      deacetylase (HDAC) inhibitors derived from conjugation of a suberoylanilide
      hydroxamic acid-like aliphatic-hydroxamate pharmacophore to a nuclear
      localization signal peptide. We found that these conjugates inhibited the histone
      deacetylase activities of HDACs 1, 2, 6, and 8 in a manner similar to
      suberoylanilide hydroxamic acid (SAHA). Notably, compound 7b showed a threefold
      improvement in HDAC 1/2 inhibition, a threefold increase in HDAC 6 selectivity
      and a twofold increase in HDAC 8 selectivity when compared to SAHA.

PMID- 19854644
TI  - Curcumin analog cytotoxicity against breast cancer cells: exploitation of a redox
      dependent mechanism.
AB  - A series of novel curcumin analogs, symmetrical dienones, were previously shown
      to possess cytotoxic, anti-angiogenic and anti-tumor activities. Analogs 1 (EF24)
      and 2 (EF31) share the dienone scaffold and serve as Michael acceptors. We
      propose that the anti-cancer effects of 1 and 2 are mediated in part by redox
      mediated induction of apoptosis. In order to support this concept, 1 and 2 were
      treated with L-glutathione (GSH) and cysteine-containing dipeptides under mild
      conditions to form colorless water-soluble adducts, which were identified by
      LC/MS. Comparison of the cytotoxic action of 1, 2 and the corresponding
      conjugates, 1-(GSH)(2) and 2-(GSH)(2), illustrated that the two classes of
      compounds exhibit essentially identical cell killing capabilities. Compared with
      the yellow, somewhat light sensitive and nearly water insoluble compounds 1 and
      2, the glutathione conjugates represent a promising new series of stable and
      soluble anti-tumor pro-drugs.

PMID- 19854645
TI  - Synthesis and PKCtheta inhibitory activity of a series of 5-vinyl phenyl
      sulfonamide-3-pyridinecarbonitriles.
AB  - A series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles were prepared and
      evaluated as PKCtheta inhibitors. Optimization resulted in the identification of
      compound 15 with an IC(50) value 0.44 nM for the inhibition of PKCtheta with 150
      fold selectivity over PKCdelta.

PMID- 19854646
TI  - From selection to caged aptamers: identification of light-dependent ssDNA
      aptamers targeting cytohesin.
AB  - Caged aptamers represent valuable tools for the spatiotemporal control of protein
      function by light. Here we describe a general route starting with the de novo
      selection process targeting cytohesin-1 and aiming at the synthesis of caged
      aptamers without the prior knowledge of detailed structural determinants of
      aptamer-target binding.

PMID- 19854647
TI  - Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity
      against Tie-2 in vitro and in vivo.
AB  - The SAR and improvement in potency against Tie2 of novel thienopyrimidine and
      thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one
      of these compounds bound to the Tie-2 kinase domain is consistent with the SAR.
      These compounds have moderate potency in cellular assays of Tie-2 inhibition,
      good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.

PMID- 19854648
TI  - Discovery of the first known small-molecule inhibitors of heme-regulated
      eukaryotic initiation factor 2alpha (HRI) kinase.
AB  - A series of indeno[1,2-c]pyrazoles were discovered to be the first known
      inhibitors of heme-regulated eukaryotic initiation factor 2alpha (HRI) kinase.
      The synthesis, structure-activity relationship profile, and in-vitro
      pharmacological characterization of this inaugural series of HRI kinase
      inhibitors are detailed.

PMID- 19854649
TI  - Discovery of highly potent and selective type I B-Raf kinase inhibitors.
AB  - A series of pyrazolo[1,5-alpha]pyrimidine analogs has been prepared and found to
      be potent and selective B-Raf inhibitors. Molecular modeling suggests they bind
      to the active conformation of the enzyme.

PMID- 19854651
TI  - Methods for objective measure, quantification and analysis of sedentary behaviour
      and inactivity.
AB  - The purpose of this study was to develop and test a generic technique to robustly
      quantify the pattern of sedentary behaviour from objective records. The technique
      was applied to four groups of subjects: a healthy group with an active occupation
      (N=54), a healthy group with a sedentary occupation (N=53), a group of subjects
      with chronic low back pain (N=5) and a group of subjects with chronic fatigue
      syndrome (N=14). This study presents the first evidence that bouts of sedentary
      activity are power law distributed. Results showed that there was no significant
      difference in total sedentary time between the groups, however, the patterns of
      accumulation of sedentary time were significantly different for the groups.
      Sedentary groups accumulated their total sedentary time from a small number of
      longer sedentary bouts. Active groups tended to break their sedentary time into a
      greater number of shorter bouts. This suggests that the power law exponent alpha
      and the GINI index G, used to describe the pattern of accumulation of sedentary
      time, could be used to evaluate and quantify sedentary behaviour.

PMID- 19854652
TI  - A comparison of multi-segment foot kinematics during level overground and
      treadmill walking.
AB  - Previous work comparing treadmill and overground walking has focused on lower
      extremity motion and kinetics, with few identified differences. However, a
      comparison of multi-segment foot kinematics between these conditions has not been
      previously reported. Sagittal ankle motion using a single rigid body foot model
      and three-dimensional hindfoot and forefoot kinematics were compared during
      barefoot, level, overground walking at a self-selected speed and treadmill
      walking at a similar speed for 20 healthy adults. Slight differences were seen in
      ankle plantarflexion and hindfoot plantarflexion during first rocker, as well as
      peak forefoot eversion and abduction, however all changes were less than 3
      degrees , and most were within the day-to-day repeatability. These results
      indicate that foot mechanics as determined using a multi-segment foot model were
      similar between overground and treadmill walking at similar speeds in healthy
      adults. Treadmill protocols may provide a controlled method to analyze a
      patient's ability to adapt to walking at different speeds and surface slopes,
      which are encountered often during ambulation of daily living.

PMID- 19854650
TI  - Heterobiaryl purine derivatives as potent antiproliferative agents: inhibitors of
      cyclin dependent kinases. Part II.
AB  - C-6 Biarylmethylamino purine derivatives of roscovitine (1) inhibit cyclin
      dependent kinases and demonstrate potent antiproliferative activity. Replacement
      of the aryl rings of the C-6 biarylmethylamino group with heterobiaryl rings has
      provided compounds with significantly improved activity. In particular,
      derivatives 18 g and 9 c demonstrated 1000-fold and 1250-fold improvements,
      respectively, in the growth inhibition of HeLa cells compared to roscovitine (1).

PMID- 19854653
TI  - Video based analysis of dynamic midfoot function and its relationship with Foot
      Posture Index scores.
AB  - INTRODUCTION: Various studies have demonstrated significant as well as non
      significant relationships between static evaluation of foot posture and injury
      likelihood. Therefore, the relationship of static and dynamic measures needs to
      be established as in clinical settings time consuming dynamic methods are often
      not feasible. PURPOSE: Assess reliability of a new method to quantify midfoot
      movement and validate the use of Foot Posture Index (FPI) classification as
      predictor of dynamic foot function during walking. METHOD: Foot type was
      classified using FPI in 280 randomly selected adult participants (mean age 43.4
      years). A Video Sequence Analysis (VSA) system was used to quantify midfoot
      kinematics during walking. Navicula drop (DeltaNH) and minimal navicula height
      (NHL) were compared with FPI. RESULTS: The Intraclass Correlation Coefficients
      (ICC) for DeltaNH and NHL ranged from 0.65 to 0.95 with a coefficient of
      repeatability of 1.4 mm for DeltaNH and 4.5 mm for NHL. System precision was
      estimated at 0.99 mm for DeltaNH and 3.18 mm for NHL. DeltaNH was significantly
      positively correlated with FPI scores while NHL decreased with increasing FPI.
      However, the FPI model predicted only 13.2% of the variation in DeltaNH and 45%
      of the variation in NHL during walking (p<0.001). CONCLUSION: The VSA was proven
      as a reliable and precise method to quantify midfoot kinematics. FPI scores and
      individual components of the FPI show strong statistical relationships to dynamic
      measures but individual predictions remain questionable. Dynamic midfoot measures
      are recommended for clinical foot assessments.

PMID- 19854654
TI  - The effect of arm movements on the lower limb during gait after a stroke.
AB  - The purpose of this study was to examine the influence of arm movements on lower
      limb movement and muscle activation during treadmill walking after a stroke. Ten
      high functioning stroke and 10 healthy subjects walked on a treadmill while
      swinging their arms naturally, and while holding onto handles that were either
      fixed in place or allowed to slide along horizontal handrails. Full-body
      kinematics were recorded, along with bilateral surface electromyography from
      lower limb muscles. Arm movements influenced lower limb muscle activity but had
      little effect on movement patterns at the joints. When handrails were present a
      small amount of weight was borne through the upper limbs, and for stroke subjects
      this was reduced when the handles were free to slide. Activity of proximal leg
      muscles during stance was affected by the weight borne through the upper limbs,
      increasing when arm movements were performed. Soleus activity during stance was
      greatest with unsupported arm movements. In stroke subjects, early stance
      tibialis anterior activity in the paretic leg was greatest with no arm movements,
      and early swing tibialis anterior activity in both legs was greatest with
      unsupported arm movements. Many of the changes in muscle activation appeared to
      be due to changes in postural stability that occurred when performing arm
      movements. Overall, results support further study of the long-term changes
      associated with the inclusion of arm movements in gait rehabilitation protocols.

PMID- 19854655
TI  - A novel method for determining ground-referenced contacts during stair ascent:
      comparing relative hip position to quiet standing hip height.
AB  - Stair climbing can be measured using body-fixed sensors, whereby the origin and
      axes of the coordinate system are fixed with respect to the geometry of a body
      segment. These sensors can be part of a portable system, which provides the
      possibility to collect data in complex real-life environments. However due to the
      fact that the sensors are body-fixed, difficulties in determining the ground
      based parameters of stair ascent can occur. The purpose of this study is to
      present a new approach for determining initial contacts based on a multi-chain
      biomechanical model combined with a new analysis method, in which relative hip
      height is compared to hip height during normal standing. Initial contacts
      obtained from the proposed method were compared to those obtained using an
      optical tracking device. An average absolute timing difference ranging from 0.04
      (SD + or - 0.03) to 0.06 (+ or - 0.03) s and a root mean square error ranging
      from 0.05 to 0.07 s were found between the two techniques. This shows that the
      new approach presented in this study can be used to accurately determine initial
      contacts during stair ascent using portable equipment.

PMID- 19854656
TI  - New measurements and evaluation of excitation functions for (p,xn), (p,pxn) and
      (p,2pxn) reactions on (133)Cs up to 70MeV proton energy.
AB  - Cross sections for production of the therapeutic radioisotope (131)Cs via the
      (133)Cs(p,3n)(131)Ba-->(131)Cs route were investigated at cyclotrons. Excitation
      functions of the (133)Cs(p,x)(133m,133mg,131mg,129g,129m,128)Ba,
      (132,129cum,127cum)Cs and (129m(ind),127cum,125cum)Xe nuclear reactions were
      measured up to 70MeV proton energy. The experimental data were compared to the
      results of model calculations performed by means of ALICE-IPPE, EMPIRE-II and
      TALYS computer codes. Good overall agreement was observed. On the basis of the
      measured excitation functions integral yields were deduced. Charged particle
      production routes of (131)Cs are discussed.

PMID- 19854657
TI  - Application of jade samples for high-dose dosimetry using the EPR technique.
AB  - The dosimeter characteristics of jade samples were studied for application in
      high-dose dosimetry. Jade is the common denomination of two silicates: jadeite
      and actinolite. The EPR spectra of different jade samples were obtained after
      irradiation with absorbed doses of 100 Gy up to 20 kGy. The jade samples present
      signals that increase with the absorbed dose (g-factors around 2.00); they can be
      attributed to electron centers. The EPR spectra obtained for the USA jade samples
      and their main dosimetric properties as reproducibility, calibration curves and
      energy dependence were investigated.

PMID- 19854658
TI  - A laparoscopic knot-tying device for minimally invasive cardiac surgery.
AB  - OBJECTIVE: Intracorporeal suturing and knot tying can complicate, prolong or
      preclude minimally invasive surgical procedures, reducing their advantages over
      conventional approaches. An automated knot-tying device has been developed to
      speed suture fixation during minimally invasive cardiac surgery while retaining
      the desirable characteristics of conventional hand-tied surgeon's knots: holding
      strength and visual and haptic feedback. A rotating slotted disc (at the
      instrument's distal end) automates overhand throws, thereby eliminating the need
      to manually pass one suture end through a loop in the opposing end. The
      electronic actuation of this disc produces left or right overhand knots as
      desired by the operator. METHODS: To evaluate the effectiveness of this
      technology, seven surgeons with varying laparoscopic experience tied knots within
      a simulated minimally invasive setting, using both the automated knot-tying tool
      and conventional laparoscopic tools. Suture types were 2/0 braided and 4/0
      monofilament. RESULTS: Mean knot-tying times were 246+/-116 s and 102+/-46 s for
      conventional and automated methods, respectively, showing an average 56%
      reduction in time per surgeon (p=0.003, paired t-test). The peak holding strength
      of each knot (the force required to break the suture or loosen the knot) was
      measured using tensile-testing equipment. These peak holding strengths were
      normalised by the ultimate tensile strength of each suture type (57.5 N and 22.1N
      for 2/0 braided and 4/0 monofilament, respectively). Mean normalised holding
      strengths for all knots were 68.2% and 71.8% of ultimate tensile strength for
      conventional and automated methods, respectively (p=0.914, paired t-test).
      CONCLUSIONS: Experimental data reveal that the automated suturing device has
      great potential for advancing minimally invasive surgery: it significantly
      reduced knot-tying times while providing equivalent or greater holding strength
      than conventionally tied knots.

PMID- 19854659
TI  - Leptin receptor modulation of adiposity and fertility.
AB  - The leptin receptor was discovered as a leptin binding protein, which is highly
      expressed in the choroid plexus. Mapping of the gene's chromosomal locations in
      rodents revealed that mutations in Lepr were the basis of obesity/diabetes
      mutations in rodents and humans. Genetic manipulations that target Lepr
      expression in specific neurons or hypothalamic areas have generated insights into
      the modes by which body composition and reproductive function are modulated by
      the leptin receptor. These animal models have also been instrumental in
      identifying diabetes susceptibility genes. In this review we discuss the evidence
      that supports the concept of networked functions of leptin receptor as it
      pertains to feeding, substrate utilization and reproduction.

PMID- 19854660
TI  - New reagents for increasing ESI multiple charging of proteins and protein
      complexes.
AB  - The addition of m-nitrobenzyl alcohol (m-NBA) was shown previously (Lomeli et
      al., J. Am. Soc. Mass Spectrom. 2009, 20, 593-596) to enhance multiple charging
      of native proteins and noncovalent protein complexes in electrospray ionization
      (ESI) mass spectra. Additional new reagents have been found to "supercharge"
      proteins from nondenaturing solutions; several of these reagents are shown to be
      more effective than m-NBA for increasing positive charging. Using the myoglobin
      protein-protoporphyrin IX (heme) complex, the following reagents were shown to
      increase ESI charging: benzyl alcohol, m-nitroacetophenone, m-nitrobenzonitrile,
      o-NBA, m-NBA, p-NBA, m-nitrophenyl ethanol, sulfolane (tetramethylene sulfone),
      and m-(trifluoromethyl)-benzyl alcohol. Based on average charge state, sulfolane
      displayed a greater charge increase (61%) than m-NBA (21%) for myoglobin in
      aqueous solutions. The reagents that promote higher ESI charging appear to have
      low solution-phase basicities and relatively low gas-phase basicities, and are
      less volatile than water. Another feature of mass spectra from some of the active
      reagents is that adducts are present on higher charge states, suggesting that a
      mechanism by which proteins acquire additional charge involves direct interaction
      with the reagent, in addition to other factors such as surface tension and
      protein denaturation.

PMID- 19854661
TI  - Elemental sulfur as a versatile low-mass-range calibration standard for laser
      desorption ionization mass spectrometry.
AB  - Facile generation of series of singly charged radical anions (S(n)(-*); n = 1-15)
      and cations (S(n)(+*); n = 2-11) by direct laser ionization renders elemental
      sulfur an excellent material for the low-mass-region calibration of time of
      flight (TOF) mass spectrometers. Upon irradiation by a 337-nm UV laser, elemental
      sulfur undergoes facile ionization without the need of an additional laser
      absorbing matrix. An intense and evenly spaced set of peaks is obtained in both
      modes.

PMID- 19854662
TI  - Removal of TSE agents by depth or membrane filtration from plasma products.
AB  - The removal of the abnormal form of prion protein i.e. PrP(SC) by filtration
      steps in the plasma fractionation process has been investigated by immuno-Western
      blotting. Depth filtration has been shown to be capable of removing scrapie by 2
      3 log from certain plasma product intermediates. These include cryoprecipitate
      supernatant, used for the manufacture of immunoglobulin and albumin, and albumin
      fraction V, by filtration using Pall Seitz or 3m Cuno depth filters respectively.
      However no significant removal occurred with immunoglobulin Fraction II after
      Cuno depth filtration. When 0.2 microm PVDF and Nylon membrane filters were
      tested, the removal of TSEs from 20% albumin was limited i.e. 0.6-1.3 log.
      However under protein free conditions using phosphate buffered saline, filtration
      was not effective in the case of a PVDF filter but very effective i.e. >2.9 log
      in the case of a Nylon filter.

PMID- 19854663
TI  - Evidence from the attentional blink for different sources of word repetition
      effects.
AB  - T2 in an attentional blink paradigm served as a high- or low-frequency prime word
      for a subsequent repeated target. Consistent with research in visual word
      identification, only reported primes facilitated the identification of a target
      repeated approximately 8s after RSVP. Priming was greater for low- than high
      frequency words. Analogous with masked priming, a blinked T2 facilitated report
      of a repeated target occurring 318ms after T2 in RSVP. The blinked repetition
      priming effect was additive with target frequency. These results indicate that:
      (1) the outcomes of processing prime words are a key factor in repetition priming
      effects, with blinked and reported T2s behaving like masked and unmasked primes,
      respectively, (2) there may be different sources of repetition effects, (3) there
      is a consistent cross-paradigm pattern of repetition effects that occurs as a
      function of prime-target interval and the ability to identify the word on its
      first and second presentation.

PMID- 19854664
TI  - Pharmacokinetics of erythromycin after intravenous, intramuscular and oral
      administration to cats.
AB  - The aim of this study was to characterise the pharmacokinetic properties of
      different formulations of erythromycin in cats. Erythromycin was administered as
      lactobionate (4 mg/kg intravenously (IV)), base (10mg/kg, intramuscularly (IM))
      and ethylsuccinate tablets or suspension (15 mg/kg orally (PO)). After IV
      administration, the major pharmacokinetic parameters were (mean +/- SD): area
      under the curve (AUC)((0-infinity)) 2.61 +/- 1.52 microgh/mL; volume of
      distribution (V(z)) 2.34 +/- 1.76L/kg; total body clearance (Cl(t)) 2.1 0 +/-
      1.37 L/hkg; elimination half-life (t(1/2)(lambda)) 0.75 +/- 0.09 h and mean
      residence time (MRT) 0.88 +/- 0.13 h. After IM administration, the principal
      pharmacokinetic parameters were (mean +/- DS): peak concentration (C(max)), 3.54
      +/- 2.16 microg/mL; time of peak (T(max)), 1.22 +/- 0.67 h; t(1/2)(lambda), 1.94
      +/- 0.21 h and MRT, 3.50 +/- 0.82 h. The administration of erythromycin
      ethylsuccinate (tablets and suspension) did not result in measurable serum
      concentrations. After IM and IV administrations, erythromycin serum
      concentrations were above minimum inhibitory concentration (MIC)(90)=0.5
      microg/mL for 7 and 1.5h, respectively. However, these results should be
      interpreted cautiously since tissue erythromycin concentrations have not been
      measured and can reach much higher concentrations than in blood, which may be
      associated with enhanced clinical efficacy.

PMID- 19854665
TI  - First principle study towards the influence of Cd2+ on the morphology of sodium
      chloride.
AB  - The influence of Cd(2+) on the morphology of sodium chloride has been
      investigated with Density functional methods. The preferential interactions of
      Cd(2+) ion with the {111} surface of NaCl support the observed octahedron
      morphology of NaCl. The calculations were performed both in the gas phase and
      aqueous phase using continuum model (COSMO). We have examined the interaction of
      Cd(2+) with various surface sites of sodium chloride such as, flat face, steps
      and kinks. The stabilization of {111} NaCl surface by mixed Cd(2+) ion and
      explicit water molecules in the ratio of (1:3) is in agreement with the SXRD
      results (Surf. Sci. 599 (2005) 196 [17]). The Cd(2+) ion prefers to interact with
      {100} surface of NaCl by surrounding with water molecules, whereas, the mixed
      layer formation on {111} is not specific in nature. The interaction of CdCl(2)
      with the surface of sodium chloride is ineffective to induce this phenomenon.

PMID- 19854666
TI  - [Variability of preanalytical errors between decentralized phlebotomy centers: a
      challenge for patient safety].
AB  - OBJECTIVE: The aim of the study is to show the most frequent preanalytical sample
      errors from distinct decentralized phlebotomy centers. METHOD: The study was
      conducted from May 2005 to March 2008. In this period 36,2054 requests and
      2,880,742 tests were received from the 16 decentralized phlebotomy centers. When
      an unsuitable sample is received specific coded results are registered as test
      results to inform the physician that an error had occurred and a new specimen
      collection is recommended. We used the the request number, which is specific for
      each phlebotomy center to ascertain where the samples with errors had been drawn,
      The preanalytical errors were identified by looking for coded results and were
      collected automatically from the LIS using a software program based on OLAP's
      cube (Omnium Roche Diagnostic), obtaining number and type of preanalytical error
      for each sample. The errors are calculated as number per million samples
      requested. Analysis of data was carried out using Microsoft Excel 2003.
      Categorical variables were expressed as frequency and percentage. RESULTS: The
      highest number of incidences occurred in urine samples (52%), followed by
      coagulation (21%), haematology (17%) and biochemistry (10%). With regard to the
      type of error, the largest proportion of errors was due to failures of process
      (62%). CONCLUSIONS: The high incidence of preanalytical errors and variability
      between centers suggests that there is a need to standardize the drawing
      practice.

PMID- 19854667
TI  - The benign nature of acute dengue infection in hospitalized older adults in
      Singapore.
AB  - OBJECTIVES: In Singapore, dengue primarily affects adults. This study aimed to
      determine if older dengue patients in Singapore have greater morbidity and
      mortality. METHODS: All laboratory diagnosed dengue patients admitted to Tan Tock
      Seng Hospital in 2004 were retrospectively reviewed. Cases were re-classified
      into dengue fever and dengue hemorrhagic fever based on World Health Organization
      criteria. Demographic, clinical, laboratory, and outcome data of patients aged >
      or = 60 years and <60 years were collected. RESULTS: Of 1971 laboratory confirmed
      dengue cases, 66 were aged > or = 60 years. Older patients were significantly
      less likely to be male (44% vs. 64%), and more likely to have diabetes (17% vs.
      2%), hypertension (48% vs. 4%), ischemic heart disease (6% vs. 0.1%),
      hyperlipidemia (18% vs. 1%), and secondary dengue infections (64% vs. 34%).
      Clinical features were similar except older patients were significantly less
      likely to report fever (92% vs. 99%), or have leukopenia (32% vs. 51%) or
      hemoconcentration (0 vs. 5%) on admission. Older patients had similar dengue
      hemorrhagic fever, bleeding, hypotension, severe thrombocytopenia, and elevated
      transaminase rates. Length of hospital stay, risk of intensive care unit
      admission, and outcome of death were not statistically different. CONCLUSIONS:
      Despite greater co-morbidity and secondary dengue infection, older dengue
      patients in Singapore did not have greater morbidity or mortality.

PMID- 19854668
TI  - Lipase maturation factor 1: its expression in Zucker diabetic rats, and effects
      of metformin and fenofibrate.
AB  - AIM: High triglyceride (TG) levels are a risk factor for cardiovascular diseases,
      and TG concentrations depend on the balance between its appearance in and
      clearance from plasma. TG clearance is controlled mainly by lipoprotein lipase
      (LPL), the maturation and activity of which are dependent on lipase maturation
      factor 1 (LMF1) protein. The present study aimed to investigate LMF1 expression
      in hypertriglyceridaemia and the regulation of its expression, as little is
      currently known of these processes. METHODS: We measured LMF1 expression (mRNA)
      in Zucker diabetic rats (ZDF) throughout the development of obesity, insulin
      resistance and diabetes, and compared it with that of control rats. We also
      determined whether fenofibrate and metformin, agents with TG-lowering activities,
      have an effect on LMF1 expression in ZDF rats. RESULTS: At 7 weeks, the ZDF rats
      were obese, insulin-resistant and hypertriglyceridaemic, and their LMF1 mRNA
      levels were - whichever tissue was investigated - comparable to those of the
      control rats. Diabetic ZDF rats (14 and 21-week-old) also had high TG levels, but
      the presence of diabetes had no effect on LMF1 expression; mRNA levels remained
      comparable to those in the controls. Although fenofibrate and metformin both
      decreased plasma TG levels, fenofibrate had no effect on LMF1 expression, whereas
      metformin increased LMF1 mRNA in heart tissue (14- and 21-week-old ZDF rats;
      P<0.01), and induced a trend towards increases in adipose tissue (14-week-old ZDF
      rats) and muscle (14- and 21-week-old ZDF rats). CONCLUSION: LMF1 expression was
      not altered in this experimental animal model of obesity, insulin resistance and
      diabetes in the presence of raised TG levels. However, metformin increased LMF1
      expression in the heart, suggesting that stimulation of LMF1 may play a part in
      its TG-lowering action.

PMID- 19854669
TI  - Drug rash with eosinophilia and systemic symptoms syndrome induced by
      sulfasalazine.

PMID- 19854670
TI  - Mimicking nature: from fundamentals to applications.

PMID- 19854671
TI  - Spatial regulation in Caulobacter crescentus.
AB  - The proper positioning of regulatory proteins has a central role in the
      organization of both prokaryotic and eukaryotic cells. Important insights into
      the principles that underlie the spatial control of cellular processes have been
      gained from studies on the asymmetric bacterium C. crescentus. In this organism,
      the cell cycle state is monitored by a complex two-component signaling network
      that feeds into the central pathways controlling gene expression, DNA replication
      and polar morphogenesis. Moreover, a sophisticated regulatory system closely
      interconnects chromosome dynamics with cell division, thus ensuring the
      generation of viable offspring. Recent work has identified several new key
      players in this intricate machinery and considerably increased our knowledge on
      the communication between the different regulatory pathways involved.

PMID- 19854672
TI  - Diode laser spectroscopy of two acetylene isotopologues ((12)C2H2, (13)C(12)CH2)
      in the 1.533 microm region for the PHOBOS-Grunt space mission.
AB  - Several line intensities of the nu(1) + nu(3)(Sigma(u)(+)) - 0(Sigma(g)(+)) bands
      of (12)C(2)H(2) and (13)C(12)CH(2) at 1.533 microm have been revised at room
      temperature. These molecular transitions were selected to measure acetylene
      within the framework of the Martian space mission PHOBOS-Grunt. In the spectral
      region ranging from 6518 to 6530 cm(-1), 10 lines of both isotopologues have been
      analyzed using a high resolution tunable diode laser spectrometer. These
      transitions are well appropriate to the monitoring of C(2)H(2) by laser
      absorption spectroscopy with standard telecommunication laser diodes. Both the
      Voigt and the Rautian models are used to fit the molecular line shape and to
      provide accurate line strengths. Our data are thoroughly compared to existing
      database (including HITRAN08) and former experimental measurements.

PMID- 19854673
TI  - Molecular structure and vibrational assignments of hippuric acid: a detailed
      density functional theoretical study.
AB  - In this study, the structural properties of hippuric acid (C(9)H(9)NO(3), HA)
      were studied using density functional theory (DFT) employing B3LYP exchange
      correlation. The geometry of the molecule was fully optimized at B3LYP/6
      311G(d,p) level of theory. There are four conformers, C1, C2, C3, and C4 for this
      molecule. The geometrical parameters and energies have been obtained for all four
      conformers from DFT. The computational results diagnose the most stable conformer
      of HA as the C1 form. The vibrational frequencies were calculated and fundamental
      vibrations were assigned based on the scaled theoretical wavenumbers. The
      complete assignments were performed on the basis of the total energy distribution
      (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM)
      method. (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the
      molecule were calculated by using the gauge-invariant atomic orbital (GIAO)
      method. A study on the electronic properties, such as HOMO and LUMO energies,
      were performed by time-dependent DFT (TD-DFT) approach, while taking solvent
      effects into account. Finally, geometric parameters, vibrational bands, chemical
      shifts and absorption wavelengths were compared with available experimental data
      of the molecule.

PMID- 19854674
TI  - Some fluorescence properties of dimethylaminochalcone and its novel cyclic
      analogues.
AB  - This paper demonstrates the basic character (polarity, solubility, colour,
      absorption and fluorescence quantum yield) of synthetic dimethylaminochalcone (1)
      and its cyclic analogues measured in toluene, chloroform, dimethylsulfoxide and
      ethanol, which have been studied by absorption and fluorescence spectroscopy. The
      biologically active dye 4'-dimethylaminochalcone (1b) and its less flexible
      analogues 4-dimethylaminoindanone (2b), -tetralone (3b), and -benzosuberone (4b)
      are lipophilic molecules that displayed the best solubility in toluene and
      chloroform. The highest fluorescence and quantum yields of compounds 1 and 2 have
      been obtained in DMSO and chloroform. Quenching effect of fluorescence compounds
      (1-4) has been studied in the mixture of the most polar organic solvents DMSO and
      water. In the presence of water, fluorescence of compound 1 has been quenched the
      best from all studied chalcones and emission maxima of molecules 1-4 have been
      shifted to the longer wavelengths. Quenching effect of fluorescence by water was
      in order 1 > 2 > 3 > 4.

PMID- 19854675
TI  - Quantum chemical and spectroscopic investigations of 5-aminoquinoline.
AB  - The Fourier transform infrared (FTIR) and FT-Raman spectra of 5-aminoquinoline
      (5AQ) have been recorded in the range 4000-400 and 3500-100 cm(-1), respectively.
      The complete vibrational assignment and analysis of the fundamental modes of the
      compounds were carried out using the observed FTIR and FT-Raman data. (1)H and
      (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule were
      calculated by using the gauge independent atomic orbital (GIAO) method. UV-vis
      spectrum of the compound was recorded and the electronic properties, such as HOMO
      and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. The
      geometric parameters, chemical shifts and absorption wavelengths were compared
      with the experimental data of the molecule. The vibrational frequencies which
      were determined experimentally are compared with those obtained theoretically
      from ab initio HF and DFT-B3LYP gradient calculations employing the 6-31G** and 6
      311++G** basis sets for optimized geometries of the compound. The interactions of
      NH-pi and the influence of amino group on the skeletal modes are investigated.

PMID- 19854676
TI  - Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal
      circulation enriched in the fetal bloodstream.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the major cause of congenital infection and
      disease leading to permanent birth defects. In about 35-40% of pregnant women
      with primary CMV infection, virus crosses the placenta, resulting in the birth of
      congenitally infected babies. In contrast, this happens in only 1-3% of
      seropositive women with strong CMV-specific humoral immunity. Whether CMV reaches
      the fetus and disseminates depends on the level of high-avidity antibodies in the
      maternal circulation and the passive immunity of the fetus. OBJECTIVES AND STUDY
      DESIGN: To identify CMV infection in uncomplicated deliveries based on detection
      of viral DNA in placental biopsy specimens at term. To quantify CMV-specific IgG
      avidity, neutralizing titer, IgG1 concentration, and characterize the immunoblot
      profiles for CMV proteins in paired samples of placental and cord blood sera.
      RESULTS: In accord with earlier reports, CMV DNA was detected in 39% (11/28) of
      placentas with mean- to high-avidity CMV-specific IgG. In seropositive women, the
      concentration of antiviral antibodies, specifically IgG1, increased in the fetal
      bloodstream, and CMV neutralizing titers in maternal and fetal blood were
      comparable. CONCLUSIONS: CMV-specific, high-avidity neutralizing antibodies from
      maternal circulation are transcytosed to the fetal bloodstream, contribute to
      suppression of viral replication in the placenta and could prevent congenital
      disease.

PMID- 19854677
TI  - The role of neutrophils in the event of intestinal inflammation.
AB  - The transmigration of polymorphonuclear leukocytes (PMNs; neutrophils) into the
      intestinal lumen is a classical phenomenon associated with a wide variety of
      disease states, including those of both pathogenic and autoimmune/idiopathic
      origin. While PMNs are highly effective at killing invading pathogens by
      releasing microbiocidal products, excessive or unnecessary release of these
      substances can cause substantial damage to the intestinal epithelium. Therefore,
      it is necessary to understand the underlying mechanisms that lure neutrophils
      into the lumen allowing them to perform their desired functions, so that
      researchers may begin to identify which processes may be potential targets for
      inhibiting the transmigration of PMNs during noninfectious states.

PMID- 19854679
TI  - Contemporary issues relating to assessment of pre-registration nursing students
      in practice.
AB  - Clinical placements are an essential part of pre-registration nurse education.
      Mentors have a vital role in providing constructive feedback and assessing the
      student throughout their placement. There have been reports of failing to fail
      students in practice, however, little evidence has been provided to support this.
      This paper provides an insight into apparent mismatches between mentor feedback
      given to students in their practice assessment documents and feedback given to
      university and Trust staff anonymously. Our findings appear to illustrate issues
      of inconsistency and a lack of ability to give accurate feedback on professional
      values and behaviours. This is in contrast to the feedback on clinical skills -
      in which the mentors appeared to be in agreement, with the written comments being
      supported by congruent scores in the relevant competencies.

PMID- 19854678
TI  - The global cysteine peptidase landscape in parasites.
AB  - The accumulation of sequenced genomes has expanded the already sizeable
      population of cysteine peptidases from parasites. Characterization of a few of
      these enzymes has ascribed key roles to peptidases in parasite life cycles and
      has also shed light on mechanisms of pathogenesis. Here we discuss recent
      observations on the physiological activities of cysteine peptidases of parasitic
      organisms, paired with a global view of all cysteine peptidases from the MEROPS
      database grouped by similarity. This snapshot of the landscape of parasite
      cysteine peptidases is complex and highly populated, suggesting that expansion of
      research beyond the few 'model' parasite peptidases is now timely.

PMID- 19854680
TI  - Secondary nocturnal enuresis caused by central sleep apnea from Chiari
      malformation type 1.
AB  - OBJECTIVE: To report a novel cause of nocturnal enuresis (NE) and highlight the
      literature giving insight into this novel mechanism. PATIENT: A 12-year-old
      morbidly obese female with 2-year history of nightly secondary monosymptomatic
      NE. RESULTS: On evaluation, a history of severe sleep disturbed breathing was
      elicited. Anticipating obstructive sleep apnea (OSA), polysomnography was
      performed, detecting severe central sleep apnea (CSA) without OSA. Brain magnetic
      resonance imaging revealed severe Chiari malformation Type I (CM1) with abnormal
      cerebrospinal fluid dynamics. She had no other classic signs or symptoms of CM1.
      Neurosurgical decompression halted the NE and normalized nocturnal breathing and
      cerebrospinal fluid dynamics, confirming that the CSA was caused by the CM1 and
      resulted in the NE. A thorough literature review found no prior reports of CSA
      induced NE. Since CSA and OSA differ by the absence of negative intrathoracic
      pressures in CSA, this case suggests that such pressures are not a key
      mechanistic component of SA-induced NE. CONCLUSION: This first report of
      secondary NE caused by CSA from CM1 emphasizes obtaining a sleep history in the
      enuretic child, introduces a new cause of NE, and challenges hypotheses
      underlying SA-induced NE.

PMID- 19854681
TI  - Intrauterine growth restriction: new standards for assessing adverse outcome.
AB  - The study of associations between intrauterine growth restriction (IUGR) and
      adverse outcome benefits from the use of a birthweight standard which is based on
      customised growth potential. Its application is able to retrospectively quantify
      the strength of the link with IUGR, whether fetal growth problems were identified
      antenatally or not. Furthermore, growth failure hitherto unrecognised by
      conventional standards, such as the average size but relatively small babies of
      mothers with high body mass index, identify IUGR as a cause of the increased
      perinatal mortality risk in obese pregnancies. Fetal growth restriction is found
      to be a frequent antecedent of perinatal morbidity and mortality, pointing to the
      need to improve its timely antenatal detection as a mainstay of management and
      prevention.

PMID- 19854682
TI  - Obstetric management of intrauterine growth restriction.
AB  - The aim of obstetric management is to identify growth-restricted foetuses at risk
      of severe intrauterine hypoxia, to monitor their health and to deliver when the
      adverse outcome is imminent. After 30-32 gestational weeks, a Doppler finding of
      absent or reverse end-diastolic flow in the umbilical artery of a small-for
      gestational age foetus is in itself an indication for delivery. In very preterm
      foetuses, the intrauterine risks have to be balanced against the risk of
      prematurity. All available diagnostic information (e.g., Doppler velocimetry of
      umbilical artery, foetal central arteries and veins and of maternal uterine
      arteries; foetal heart rate with computerised analysis of short-term variability;
      amniotic fluid amount; and foetal gestational age-related weight) should be
      collected to support the timing of delivery. If possible, the delivery should
      optimally take place before the onset of late signs of foetal hypoxia
      (pathological foetal heart rate pattern, severely abnormal ductus venosus blood
      velocity waveform, pulsations in the umbilical vein).

PMID- 19854683
TI  - Asomatognosia P. Bonnier. L'aschematie. Revue Neurol 1905;13:605-9.

PMID- 19854684
TI  - Conversational displays of coping resources in clinical encounters between
      patients with epilepsy and neurologists: a pilot study.
AB  - How people with epilepsy (PWE) cope is an important determinant of their
      resilience to seizures. More adaptive ways of coping are an independent predictor
      of health-related quality of life. Coping styles have typically been assessed
      using self-report questionnaires. However, such questionnaires fail to capture
      the complexity of the phenomenon of coping. This study explores whether close
      examination of the interactional and linguistic resources used by PWE can be used
      to enhance our understanding of coping behavior as it naturally emerges in
      semistructured, first clinical encounters between patients with refractory
      epilepsy and a neurologist. At a more superficial (topical) level of analysis,
      our examination of nine interactions reveals that PWE tend to present themselves
      as resourceful individuals who are in control of their disorder (which thereby
      becomes less significant). In contrast, the analysis of more subtle linguistic
      and interactional features indicates that some PWE actually find their disorder
      quite difficult to deal with.

PMID- 19854685
TI  - Penile brachytherapy: technical aspects and postimplant issues.
AB  - PURPOSE: Squamous carcinoma (SCC) of the penis affects about 1 in 100,000 men in
      western societies. Interstitial brachytherapy can be an effective penis
      conserving modality for T1, T2, and selected T3 tumors. Unfortunately, few
      radiation oncology trainees have the opportunity to treat a case of penile cancer
      during their residency, and few centers have brachytherapy expertise for this
      tumor site. We report our technique that has been developed and refined over the
      past 20 years. MATERIALS AND METHODS: From 1989 to 2009, we have been using
      brachytherapy to treat penile SCC and have experience with 75 cases. From 1989 to
      1998, manual afterloading was used with (192)Ir wire or seeds, and from 1999 to
      the present, pulse dose rate automated afterloading. Sixty Gray is delivered over
      a period of 4-5 days. RESULTS: Patient selection for penile brachytherapy and the
      technical and dosimetric aspects of the procedure will be discussed along with
      posttreatment care and followup. CONCLUSIONS: Brachytherapy is an effective
      treatment for T1, T2, and selected T3 SCC of the penis. Efficacy depends on
      careful planning and appreciation of dosimetry.

PMID- 19854686
TI  - Interaction of surface-attached haemoglobin with hydrophobic anions monitored by
      on-line acoustic wave detector.
AB  - The behaviour of proteins on surfaces and at interfaces is an important field
      with applications in drug development, clinical diagnostics and studies of device
      biocompatibility. A key factor is the conformation of surface-bound proteins,
      which can affect chemical signalling and drug binding. A recent study of the
      interactions of haemoglobin with hydrophobic anions at a liquid-liquid interface
      has shown that a pH- and orientation-dependent conformational change occurs in
      the haemoglobin molecule upon interaction with these anions. To corroborate these
      results, we use an acoustic wave detector to study binding of solution-phase
      hydrophobic anions to surface-adhered haemoglobin. The orientation of protein is
      controlled by thiol chemistry, which generates hydrophilic and hydrophobic
      surfaces. Tetraphenylborate-based anions are introduced to the haemoglobin coated
      surface via an on-line flow-injection system to monitor the signal in real-time.
      Changes in the acoustic properties of the surface, measured piezoelectrically,
      are related to interactions between the protein and the anions. Signal strength
      is proportional to the degree of interaction between the salts and the
      haemoglobin, which in turn, is influenced by its conformation.

PMID- 19854687
TI  - Specific targeted gene repair using single-stranded DNA oligonucleotides at an
      endogenous locus in mammalian cells uses homologous recombination.
AB  - The feasibility of introducing point mutations in vivo using single-stranded DNA
      oligonucleotides (ssON) has been demonstrated but the efficiency and mechanism
      remain elusive and potential side effects have not been fully evaluated.
      Understanding the mechanism behind this potential therapy may help its
      development. Here, we demonstrate the specific repair of an endogenous non
      functional hprt gene by a ssON in mammalian cells, and show that the frequency of
      such an event is enhanced when cells are in S-phase of the cell cycle. A
      potential barrier in using ssONs as gene therapy could be non-targeted mutations
      or gene rearrangements triggered by the ssON. Both the non-specific mutation
      frequencies and the frequency of gene rearrangements were largely unaffected by
      ssONs. Furthermore, we find that the introduction of a mutation causing the loss
      of a functional endogenous hprt gene by a ssON occurred at a similarly low but
      statistically significant frequency in wild type cells and in cells deficient in
      single strand break repair, nucleotide excision repair and mismatch repair.
      However, this mutation was not induced in XRCC3 mutant cells deficient in
      homologous recombination. Thus, our data suggest ssON-mediated targeted gene
      repair is more efficient in S-phase and involves homologous recombination.

PMID- 19854688
TI  - V-Y gastrocnemius muscle slide with turnover fascial flap for compound Achilles
      defects: a simple solution.
AB  - BACKGROUND: Compound defects of the Achilles region pose a reconstructive
      challenge. Poor vascularity of the Achilles region predisposes to complications.
      Repair of the tendon with simultaneous soft-tissue cover gives the patient the
      best chance to recover. MATERIALS AND METHODS: Gastrocnemius musculotendinous V-Y
      slide for Achilles tendon defect with non-axial turnover fascial flaps based on
      the proximal end of the defect with a split-skin graft on the fascial flap was
      used in two patients. The vascular bases of such flaps and the technical details
      has been discussed. RESULTS: The functional and aesthetic results were highly
      satisfactory with minimal donor-site morbidity. The flap was thin enough to fit
      the contour of the Achilles region. The fascial flap with skin graft was durable
      and withstood footwear well. The flap also allowed tendon gliding beneath it,
      with near-complete movements at the ankle joint. CONCLUSION: Large flaps can
      sufficiently be raised with a wide base to cover small- to medium-sized defects.
      It is a good, rapid and cost-effective solution for a difficult clinical problem.

PMID- 19854690
TI  - A rare cause of non discal sciatica: schwannoma of the sciatic nerve.
AB  - Schwannomas are peripheral nerve sheath tumors. Schwannomas arising in the
      sciatic nerve are considered a rare condition. Their symptomatology usually
      mimics sciatic pain due to a herniated disc, which can delay the diagnosis. We
      report the case of a patient with chronic sciatica in whom Magnetic Resonance
      Imaging (MRI) examination of the right thigh revealed a tumor of the sciatic
      nerve. Excision of the tumor was easily performed without neural lesioning.
      Histopathological examination revealed the tumor to be a schwannoma. No
      neurologic deficit was noted postoperatively which confirms the good prognosis of
      this tumor.

PMID- 19854689
TI  - Pluripotency genes overexpressed in primate embryonic stem cells are localized on
      homologues of human chromosomes 16, 17, 19, and X.
AB  - While human embryonic stem cells (hESCs) are predisposed toward chromosomal
      aneploidities on 12, 17, 20, and X, rendering them susceptible to transformation,
      the specific genes expressed are not yet known. Here, by identifying the genes
      overexpressed in pluripotent rhesus ESCs (nhpESCs) and comparing them both to
      their genetically identical differentiated progeny (teratoma fibroblasts) and to
      genetically related differentiated parental cells (parental skin fibroblasts from
      whom gametes were used for ESC derivation), we find that some of those
      overexpressed genes in nhpESCs cluster preferentially on rhesus chromosomes 16,
      19, 20, and X, homologues of human chromosomes 17, 19, 16, and X, respectively.
      Differentiated parental skin fibroblasts display gene expression profiles closer
      to nhpESC profiles than to teratoma cells, which are genetically identical to the
      pluripotent nhpESCs. Twenty over- and underexpressed pluripotency modulators,
      some implicated in neurogenesis, have been identified. The overexpression of some
      of these genes discovered using pedigreed nhpESCs derived from prime embryos
      generated by fertile primates, which is impossible to perform with the
      anonymously donated clinically discarded embryos from which hESCs are derived,
      independently confirms the importance of chromosome 17 and X regions in
      pluripotency and suggests specific candidates for targeting differentiation and
      transformation decisions.

PMID- 19854691
TI  - Long-term result of a pure tibiotalar dislocation in a child.
AB  - Pure ankle dislocation without fracture is a very rare injury in children. We
      report the case of a 9-year-old patient who sustained open medial dislocation of
      the tibiotalar joint without fracture. The management, contributive factors, and
      long-term results are reported with a review of the literature.

PMID- 19854692
TI  - Effectiveness of nitrous oxide and analgesic cream (lidocaine and prilocaine) for
      prevention of pain during intramuscular botulinum toxin injections in children.
AB  - AIMS: To evaluate the effectiveness of an analgesic protocol with nitrous oxide
      and anaesthetic cream (lidocaine and prilocaine, EMLA) for children undergoing
      botulinum toxin injections. PATIENTS AND METHODS: Prospective study including 51
      injection sessions, 34 children with a mean age of 5.94 (range 2-15) and 209
      injected muscles. Pain was evaluated with the Children's Hospital of Eastern
      Ontario Pain Scale (CHEOPS), the Visual Analogue Scale (VAS) and the Face Pain
      Scale (FPS) for the children and with a VAS for the parents. RESULTS: CHEOPS
      score for the 51 sessions was 8.50 (S.D. 3.56). Forty-nine percent of scores were
      above the therapeutic threshold of 9; 25% of the children evaluated the pain
      above the therapeutic threshold of 3; 44.74% of the parents' estimations exceeded
      3. No correlation was found between age, weight, number of injected muscle and
      CHEOPS score. CONCLUSION: The association of MEOPA and anaesthetic cream is only
      effective for 50% of children. This is much lower than treatments for other types
      of acute induced pain in children. Botulinum toxin injections and cerebral palsy
      children present certain specificities which require improvements in this
      analgesic protocol.

PMID- 19854694
TI  - [Imaging in oncology and international rules for evaluation: the nuclear
      medicine].
AB  - The growing success of isotopic explorations in oncology is related to the number
      of growing radiotracers and progress in the methods for detection and imaging.
      Today, the nuclear medicine is able to answer important questions raised by
      biology and therapeutic progress results from this. The new radiopharmaceutical
      compounds are able to explore in vivo the metabolism, the proliferation, the
      hypoxia and the expression of some receptors or antigens in tumor cells. This
      progress in radiopharmaceuticals design can be combined with the new tools for
      detection, such as the cameras coupled to a tomodensitometer (TEMP-TDM and TEP
      TDM), the new gamma cameras with semiconductors, and the peroperative gamma
      probes. The nuclear medicine can now be used to determine the initial staging of
      tumours, the evaluation of residual disease, the detection of recurrence, the
      evaluation and the prediction of response to treatments, i.e. chemotherapy,
      radiotherapy and now targeted treatments. This led to very promising prospects in
      the therapeutic adaptation and in the patient follow-up, as clearly shown in the
      malignant lymphomas. Standardized international criteria are set up for the
      therapeutic evaluation in TEP-FDG. Today, the nuclear medicine belongs to the
      family of "markers of substitution", participating more and more to the
      personalized medicine field.

PMID- 19854693
TI  - Tobacco use, body mass and cancer mortality in Mumbai Cohort Study.
AB  - BACKGROUND: Tobacco use and body mass are major risk factors for many cancers.
      Despite this, very little is known about their combined effect on cancer
      mortality. These relationships are virtually unexplored in populations having
      patterns of both tobacco use and body habitus atypical of those typically
      enrolled in epidemiologic studies. METHODS: A prospective cohort study of 148,173
      men and women aged > or =35 years was conducted in Mumbai, India. Subjects were
      recruited during 1991-1997, measured for a variety of risk factors, including
      tobacco use and anthropometry, and then followed for approximately 5-6 years.
      RESULTS: During 774,129 person-years of follow up, a total of 796 cancer deaths
      were observed. Tobacco use, especially smoking in men, was associated with
      particularly high risk of death in extreme categories of body mass. At highest
      risk were underweight smoking males [hazard ratio (HR)=9.45, 5.87, and 5.75 for
      those smokers who were extremely thin (<16.0kg/m(2)), very thin (16.0 to
      <17.0kg/m(2)), or thin (17.0 to <18.5), respectively]. Significant effects of
      underweight among never and smokeless tobacco users disappeared with exclusion of
      individuals with < or =2 years of follow up. Extremely thin (<16.0kg/m(2)) women
      smokeless tobacco users had an elevation in risk, HR=2.95, that actually appeared
      to increase (to 3.21) with exclusion of individuals who were diagnosed within 2
      years of follow up. CONCLUSION: Tobacco use and undernutrition are known to be
      serious problems in developing countries. The current study underlines the
      strikingly elevated risk of cancer when they occur together.

PMID- 19854695
TI  - Airway inflammation in cement production workers.
AB  - OBJECTIVE: Cement aerosol exposure is associated with increased morbidity of
      airway disease among exposed workers. Our aim was to compare levels of
      inflammatory cells and soluble inflammatory markers in induced sputum samples
      from cement production workers between exposed and unexposed periods, and to
      compare these variables between cement workers and references. METHODS: 35
      healthy, non-smoking aerosol-exposed cement production workers from Norway
      provided a blood sample and performed induced sputum and spirometry after 5 days
      without exposure and during a period of exposure. These values were compared with
      those from an internal low-exposed reference group of 15 office workers and an
      external reference group of 39 non-exposed workers. Differential cell counts and
      inflammatory markers were assessed. RESULTS: Median thoracic aerosol
      concentration over one work shift (8 h) was 0.6 mg/m(3) (range 0.2-8.1) in
      maintenance workers and 1.75 mg/m(3) (0.2-15.5) in furnace department workers.
      The median percentage of airway neutrophils in both groups combined was 51% (32
      66) in the exposed period, which was significantly higher than in both the
      unexposed period (38%; 23-55) (p=0.04) and the external reference group (30%; 19
      44) (p=0.001). Median interleukin-1beta concentration was elevated compared with
      both office workers (p=0.05) and the external reference group (p=0.006).
      CONCLUSIONS: A significantly higher percentage of neutrophils was observed in
      cement production workers during the exposed period compared with both the non
      exposed period and the external reference group, and corresponded with elevated
      IL-1beta concentration. These data indicate that cement aerosol exposure in
      concentrations below the Norwegian occupational limits (respirable dust 5
      mg/m(3); total dust 10 mg/m(3)) may cause airway inflammation.

PMID- 19854696
TI  - Benzo[a]pyrene-induced neurobehavioral function and neurotransmitter alterations
      in coke oven workers.
AB  - OBJECTIVE: To study alterations in neurobehavioral function and neurotransmitter
      levels in coke oven workers occupationally exposed to benzo[a]pyrene (B[a]P) and
      explore possible biomarkers of B[a]P neurotoxicity. METHODS: 176 coke oven
      workers occupationally exposed to B[a]P and 48 warehouse workers (controls) were
      investigated by questionnaire. Emotional and cognitive function was investigated
      using the WHO/NCTB. B[a]P concentrations in the working environment,
      concentrations of monoamine and amino acid neurotransmitters, and levels of
      urinary 1-hydroxypyrene (1-OH-Py) were assayed by HPLC. Spectrophotometry was
      used to determine choline neurotransmitter concentrations. RESULTS: Airborne
      B[a]P concentrations were higher in the coke oven plant than in the controls'
      workplace, and 1-OH-Py levels were significantly increased in coke workers
      compared to controls (p=0.000). Digital span and order digital span scores
      indicated that learning and memory were significantly decreased in coke oven
      workers (p=0.006). Concentrations of norepinephrine (NE), dopamine, 5
      hydroxytryptamine and homovanillic acid were lower, while levels of 5
      hydroxyindoleacetic acid were higher in the exposed group compared to controls;
      the difference in NE was significant (p=0.000). Aspartic acid and gamma
      aminobutyric acid levels were significantly decreased in coke oven workers
      compared to controls (p=0.004 and p=0.004). Acetylcholine (Ach) concentration was
      four- to fivefold greater in coke oven workers than in controls, while
      acetylcholine esterase (AchE) activity was significantly decreased (p=0.000 and
      p=0.012). Statistical analysis showed that digital span and order digital span
      scores were negatively correlated to Ach and positively correlated to AchE.
      CONCLUSION: Occupational B[a]P exposure may reduce coke oven workers'
      neurobehavioral function and monoamine, amino acid and choline neurotransmitter
      levels. Moreover, Ach and AchE correlated with neurobehavioral function; AchE has
      poor specificity, but Ach is a potential biomarker of B[a]P neurotoxicity in coke
      oven workers.

PMID- 19854697
TI  - Diagnostic strategies using physical examination are minimally useful in defining
      carpal tunnel syndrome in population-based research studies.
AB  - OBJECTIVE: We evaluated the utility of physical examination manoeuvres in the
      prediction of carpal tunnel syndrome (CTS) in a population-based research study.
      METHODS: We studied a cohort of 1108 newly employed workers in several
      industries. Each worker completed a symptom questionnaire, a structured physical
      examination and nerve conduction study. For each hand, our CTS case definition
      required both median nerve conduction abnormality and symptoms classified as
      "classic" or "probable" on a hand diagram. We calculated the positive predictive
      values and likelihood ratios for physical examination manoeuvres in subjects with
      and without symptoms. RESULTS: The prevalence of CTS in our cohort was 1.2% for
      the right hand and 1.0% for the left hand. The likelihood ratios of a positive
      test for physical provocative tests ranged from 2.0 to 3.3, and those of a
      negative test from 0.3 to 0.9. The post-test probability of positive testing was
      <50% for all strategies tested. CONCLUSION: Our study found that physical
      examination, alone or in combination with symptoms, was not predictive of CTS in
      a working population. We suggest using specific symptoms as a first-level
      screening tool, and nerve conduction study as a confirmatory test, as a case
      definition strategy in research settings.

PMID- 19854698
TI  - Identifying pesticide use patterns among flower growers to assess occupational
      exposure to mixtures.
AB  - OBJECTIVES: Exposure assessment to a single pesticide does not capture the
      complexity of the occupational exposure. Recently, pesticide use patterns
      analysis has emerged as an alternative to study these exposures. The aim of this
      study is to identify the pesticide use pattern among flower growers in Mexico
      participating in the study on the endocrine and reproductive effects associated
      with pesticide exposure. METHODS: A cross-sectional study was carried out to
      gather retrospective information on pesticide use applying a questionnaire to the
      person in charge of the participating flower growing farms. Information about
      seasonal frequency of pesticide use (rainy and dry) for the years 2004 and 2005
      was obtained. Principal components analysis was performed. RESULTS: Complete
      information was obtained for 88 farms and 23 pesticides were included in the
      analysis. Six principal components were selected, which explained more than 70%
      of the data variability. The identified pesticide use patterns during both years
      were: 1. fungicides benomyl, carbendazim, thiophanate and metalaxyl (both
      seasons), including triadimephon during the rainy season, chlorotalonyl and
      insecticide permethrin during the dry season; 2. insecticides oxamyl, biphenthrin
      and fungicide iprodione (both seasons), including insecticide methomyl during the
      dry season; 3. fungicide mancozeb and herbicide glyphosate (only during the rainy
      season); 4. insecticides metamidophos and parathion (both seasons); 5.
      insecticides omethoate and methomyl (only rainy season); and 6. insecticides
      abamectin and carbofuran (only dry season). Some pesticides do not show a clear
      pattern of seasonal use during the studied years. CONCLUSIONS: The principal
      component analysis is useful to summarise a large set of exposure variables into
      smaller groups of exposure patterns, identifying the mixtures of pesticides in
      the occupational environment that may have an interactive effect on a particular
      health effect.

PMID- 19854699
TI  - Primary care consultations and costs among HIV-positive individuals in UK primary
      care 1995-2005: a cohort study.
AB  - OBJECTIVES: To investigate the role of primary care in the management of HIV and
      estimate primary care-associated costs at a time of rising prevalence. METHODS:
      Retrospective cohort study between 1995 and 2005, using data from general
      practices contributing data to the UK General Practice Research Database.
      Patterns of consultation and morbidity and associated consultation costs were
      analysed among all practice-registered patients for whom HIV-positive status was
      recorded in the general practice record. RESULTS: 348 practices yielded 5504
      person-years (py) of follow-up for known HIV-positive patients, who consult in
      general practice frequently (4.2 consultations/py by men, 5.2 consultations/py by
      women, in 2005) for a range of conditions. Consultation rates declined in the
      late 1990s from 5.0 and 7.3 consultations/py in 1995 in men and women,
      respectively, converging to rates similar to the wider population. Costs of
      consultation (general practitioner and nurse, combined) reflect these changes, at
      pound100.27 for male patients and pound117.08 for female patients in 2005.
      Approximately one in six medications prescribed in primary care for HIV-positive
      individuals has the potential for major interaction with antiretroviral
      medications. CONCLUSION: HIV-positive individuals known in general practice now
      consult on a similar scale to the wider population. Further research should be
      undertaken to explore how primary care can best contribute to improving the
      health outcomes of this group with chronic illness. Their substantial use of
      primary care suggests there may be potential to develop effective integrated care
      pathways.

PMID- 19854700
TI  - Using mathematical modelling to estimate the impact of periodic presumptive
      treatment on the transmission of sexually transmitted infections and HIV among
      female sex workers.
AB  - BACKGROUND: In settings with poor sexually transmitted infection (STI) control in
      high-risk groups, periodic presumptive treatment (PPT) can quickly reduce the
      prevalence of genital ulcers, Neisseria gonorrhoeae (NG) and Chlamydia
      trachomatis (CT). However, few studies have assessed the impact on HIV.
      Mathematical modelling is used to quantify the likely HIV impact of different PPT
      interventions. METHODS: A mathematical model was developed to project the impact
      of PPT on STI/HIV transmission amongst a homogeneous population of female sex
      workers (FSWs) and their clients. Using data from Johannesburg, the impact of PPT
      interventions with different coverages and PPT frequencies was estimated. A
      sensitivity analysis explored how the projections were affected by different
      model parameters or if the intervention was undertaken elsewhere. RESULTS:
      Substantial decreases in NG/CT prevalence are achieved among FSWs receiving PPT.
      Although less impact is achieved among all FSWs, large decreases in NG/CT
      prevalence (>50%) are possible with >30% coverage and supplying PPT every month.
      Higher PPT frequencies achieve little additional impact, whereas improving
      coverage increases impact until NG/CT becomes negligible. The impact on HIV
      incidence is smaller, longer to achieve, and depends heavily on the assumed NG/CT
      cofactors, whether they are additive, the assumed STI/HIV transmission
      probabilities and STI durations. Greater HIV impact can be achieved in settings
      with lower sexual activity (except at high coverage), less STI treatment or high
      prevalences of Haemophilus ducreyi. CONCLUSIONS: Despite the model's assumption
      of homogeneous risk behaviour probably resulting in optimistic projections, and
      uncertainty in STI cofactors and transmission probabilities, projections suggest
      PPT interventions with sufficient coverage (> or = 40%) and follow-up (> or = 2
      years) could noticeably decrease the HIV incidence (>20%) among FSW populations
      with inadequate STI treatment.

PMID- 19854701
TI  - Utilising the internet to test for sexually transmitted infections: results of a
      survey and accuracy testing.
AB  - BACKGROUND: Searching the internet for information about sexually transmitted
      infections (STI) is common. The goal of the study was to discover which internet
      sites offer STI tests and obtain information about the services and their
      validity. METHODS: Using internet web-based search engines, information was
      collected from the sites about STI testing services, costs and types of tests
      offered, and tests were evaluated for accuracy. 'Business' functions regarding
      consent and return of results were investigated. Contact attempts were made by
      phone, e-mail or 'contact us' links and by mail. Test kits were ordered from six
      commercial internet sites and one public health site. Their accuracy was
      evaluated for chlamydia and gonorrhoea. RESULTS: The study identified 27
      national/international internet sites offering STI self-collection kits and
      services. Tests were available for gonorrhoea, syphilis, chlamydia, HIV, herpes,
      hepatitis viruses, trichomonas, mycoplasma and 'gardnerella'. All attempts to
      administer the survey yielded unsatisfactory results. After sending the survey by
      mail/e-mail to all the sites, four responded, two with the survey. Six websites
      appeared invalid based on non-deliverable e-mails and returned letters. The
      remainder did not respond. Test results were obtained from five of seven ordered
      kits. Two websites who were sent mocked urine specimens never provided results.
      The two 'perform-it-yourself' kits yielded false-negative results. Two mail-in
      urine specimens yielded correct positive results. The public health site kit
      yielded correct positive results. CONCLUSIONS: The internet STI testing sites
      were difficult to contact and demonstrated unwillingness to answer consumer
      specific questions. Test accuracy varied, with home tests having poor accuracy
      and mail-in specimens demonstrating high accuracy.

PMID- 19854702
TI  - Assessment of attitudes and practices of providers of services for individuals at
      high risk of HIV and sexually transmitted infections in Karnataka, south India.
AB  - BACKGROUND: A key component of prevention programmes aimed at reducing the risk
      of HIV and sexually transmitted infections (STI) among high-risk groups such as
      female sex workers (FSW) is the provision of quality STI services. The attitudes
      and practices of care providers are critical factors in the provision of services
      and in achieving better participation of high-risk individuals in accessing
      services. OBJECTIVES: To assess the attitudes and practices of STI care providers
      towards FSW, and the perceptions of FSW towards STI services, following training.
      METHODOLOGY: After an intensive physician capacity building programme, 393 exit
      interviews of FSW were conducted following clinical encounters, and discussions
      were held with 131 STI care providers (physicians) across several districts in
      Karnataka. Focus group discussions were held among FSW to understand the
      perceptions of non-users of services. RESULTS: 60% of women reported that the
      clinics were accessible. 76% of the women who visited clinics for STI
      consultations were offered a speculum examination. 85% received a condom
      demonstration, but only 52% were advised for partner treatment. 69% of women were
      referred for HIV testing. 79% of physicians felt that sex workers were
      responsible for spreading HIV in the community, and 47% believed that sex work
      should be banned to control HIV. CONCLUSIONS: Following physician training,
      quality of care appears to be generally acceptable, but it is important to
      improve further the attitudes of providers towards sex work, and improve
      practices such as speculum examination and partner referral that can enhance
      quality of care.

PMID- 19854703
TI  - HIV prevalence and related risk factors among male sex workers in Shenzhen,
      China: results from a time-location sampling survey.
AB  - BACKGROUND: HIV transmission among men who have sex with men has recently become
      a major concern in China. Little is known, however, about HIV transmission among
      male sex workers (MSW). This study aimed to investigate HIV infection prevalence
      and risk factors among MSW in Shenzhen, China. MATERIALS AND METHODS: Following
      formative research, a cross-sectional study was conducted using time-location
      sampling among MSW in Shenzhen, from April to July 2008. Behavioural and
      serological data on HIV and syphilis were collected. The risk factors for HIV
      infection were analysed using a logistic regression model. RESULTS: In total, 394
      MSW were recruited for the survey. The prevalence of HIV and syphilis among these
      workers was 5.3% and 14.3%, respectively. Only a quarter of the MSW self
      identified as homosexual. More than 70% had sex with both men and women. HIV
      related knowledge levels were high regardless of HIV serostatus. Consistent
      condom use was low (37.1%) and varied by type of sexual partner. Factors
      including more non-commercial male partners, working in small home-based family
      clubs, being drunk before sexual intercourse, having a history of HIV tests,
      syphilis infection and a short period of residence in Shenzhen were associated
      with an increased risk of HIV infection. CONCLUSIONS: High-risk sexual practices
      were common among MSW regardless of their high level of HIV awareness. The
      working venues were associated with HIV infection and a recent test for HIV was a
      potential predictor of HIV infection. The time-location sampling method was found
      to be an appropriate way of recruiting MSW for this study, especially those
      without fixed working places.

PMID- 19854704
TI  - Serological reactivity and bacterial genotypes in Chlamydia trachomatis
      urogenital infections in Guadeloupe, French West Indies.
AB  - OBJECTIVES: To determine the prevalence and genotypes of Chlamydia trachomatis
      urogenital infection in Guadeloupe, French West Indies, and to compare C
      trachomatis direct detection to serological testing. METHODS: From March to
      November 2000, 971 consecutive patients (888 women and 83 men) who had been
      referred to the clinical laboratory of the Institut Pasteur de la Guadeloupe for
      routine testing for genital infection were recruited. Samples were subjected to a
      nucleic acid amplification assay (AMP CT, Gen-Probe, San Diego, California, USA).
      Genotypes were determined by omp1 PCR-restriction fragment length polymorphism
      analysis. Serological testing was carried out with the commercially available
      peptide-based ELISA assay (SERO-CT IgG/IgA, Savyon/BMD, Marne-La-Vallee, France).
      RESULTS: Positive AMP CT test results were obtained for 102 (10.5%) of the 971
      samples. The prevalence of infection was 16.9% in men and 9.8% in women. The most
      common genotypes were E (34.3%), F (23.9%), Da (13.4%), I (9%) and Ia (7.5%). No
      relationship was found between genogroups and age, sex or clinical symptoms. With
      AMP CT used as a reference, the sensitivity, specificity, positive and negative
      predictive values of SERO-CT were 81.1%, 56%, 34.5% and 91.2%, respectively, for
      IgG and 55.4%, 76.8%, 59.4% and 85.8%, respectively, for IgA. IgG seroprevalence
      rates were very low (1/5, 20%) in patients infected with genotype Ia strains.
      CONCLUSIONS: The prevalence found in Guadeloupe did not differ significantly from
      that found in mainland France. The genotypes Da, F, I and Ia were more prevalent
      in Guadeloupe; however, the SERO-CT assay was unable to detect serum antibodies
      in 80% of the patients infected with genotype Ia strains.

PMID- 19854705
TI  - Statin use in rheumatoid arthritis in relation to actual cardiovascular risk:
      evidence for substantial undertreatment of lipid-associated cardiovascular risk?
AB  - BACKGROUND: Cardiovascular disease (CVD) is partially attributed to traditional
      cardiovascular risk factors, which can be identified and managed based on risk
      stratification algorithms (Framingham Risk Score, National Cholesterol Education
      Program, Systematic Cardiovascular Risk Evaluation and Reynolds Risk Score). We
      aimed to (a) identify the proportion of at risk patients with rheumatoid
      arthritis (RA) requiring statin therapy identified by conventional risk
      calculators, and (b) assess whether patients at risk were receiving statins.
      METHODS: Patients at high CVD risk (excluding patients with established CVD or
      diabetes) were identified from a cohort of 400 well characterised patients with
      RA, by applying risk calculators with or without a x1.5 multiplier in specific
      patient subgroups. Actual statin use versus numbers eligible for statins was also
      calculated. RESULTS: The percentage of patients identified as being at risk
      ranged significantly depending on the method, from 1.6% (for 20% threshold global
      CVD risk) to 15.5% (for CVD and cerebrovascular morbidity and mortality) to 21.8%
      (for 10% global CVD risk) and 25.9% (for 5% CVD mortality), with the majority of
      them (58.1% to 94.8%) not receiving statins. The application of a 1.5 multiplier
      identified 17% to 78% more at risk patients. CONCLUSIONS: Depending on the risk
      stratification method, 2% to 26% of patients with RA without CVD have
      sufficiently high risk to require statin therapy, yet most of them remain
      untreated. To address this issue, we would recommend annual systematic screening
      using the nationally applicable risk calculator, combined with regular audit of
      whether treatment targets have been achieved.

PMID- 19854706
TI  - Association of IRF5 polymorphisms with activation of the interferon alpha
      pathway.
AB  - OBJECTIVE: The genetic association of interferon regulatory factor 5 (IRF5) with
      systemic lupus erythematosus (SLE) susceptibility has been convincingly
      established. To gain understanding of the effect of IRF5 variation in individuals
      without SLE, a study was undertaken to examine whether such genetic variation
      predisposes to activation of the interferon alpha (IFNalpha) pathway. METHODS:
      Using a computer simulated approach, 14 single nucleotide polymorphisms (SNPs)
      and haplotypes of IRF5 were tested for association with mRNA expression levels of
      IRF5, IFNalpha and IFN-inducible genes and chemokines in lymphoblastoid cell
      lines (LCLs) from individuals of European (CEU), Han Chinese (CHB), Japanese
      (JPT) and Yoruba Nigerian (YRI) backgrounds. IFN-inducible gene expression was
      assessed in LCLs from children with SLE in the presence and absence of IFNalpha
      stimulation. RESULTS: The major alleles of IRF5 rs13242262 and rs2280714 were
      associated with increased IRF5 mRNA expression levels in the CEU, CHB+JPT and YRI
      samples. The minor allele of IRF5 rs10488631 was associated with increased IRF5,
      IFNalpha and IFN-inducible chemokine expression in CEU (p(c)=0.0005, 0.01 and
      0.04, respectively). A haplotype containing these risk alleles of rs13242262,
      rs10488631 and rs2280714 was associated with increased IRF5, IFNalpha and IFN
      inducible chemokine expression in CEU LCLs. In vitro studies showed specific
      activation of IFN-inducible genes in LCLs by IFNalpha. CONCLUSIONS: SNPs of IRF5
      in healthy individuals of a number of ethnic groups were associated with
      increased mRNA expression of IRF5. In European-derived individuals, an IRF5
      haplotype was associated with increased IRF5, IFNalpha and IFN-inducible
      chemokine expression. Identifying individuals genetically predisposed to
      increased IFN-inducible gene and chemokine expression may allow early detection
      of risk for SLE.

PMID- 19854707
TI  - Increased accumulation of advanced glycation endproducts in patients with
      Wegener's granulomatosis.

PMID- 19854708
TI  - Total cholesterol and LDL levels decrease before rheumatoid arthritis.
AB  - OBJECTIVES: To compare lipid profiles in patients with rheumatoid arthritis (RA)
      and in non-RA subjects during the 5 years before and 5 years after the RA
      incidence/index date. METHODS: Lipid measures were abstracted in a population
      based incident cohort of patients with RA (1987 American College of Rheumatology
      criteria) first diagnosed between 1 January 1988 and 1 January 2008 and in non-RA
      subjects. Random-effects models adjusting for age, sex and calendar year were
      used to examine trends in lipid profiles, accounting for multiple measurements
      for each subject. RESULTS: The study population included a cohort of 577 patients
      with RA (a total of 3088 lipid measurements) and 540 non-RA subjects (a total of
      3048 lipid measurements). There were significant decreases in total (TC) and low
      density lipoprotein cholesterol (LDL) levels in the RA cohort during the 5 years
      before RA, compared with the non-RA cohort (p<0.001). Decreases of 0.58 mmol/l
      for TC and 0.61 mmol/l for LDL were noted in RA compared with decreases of 0.09
      mmol/l for TC and 0.22 mmol/l for LDL in the non-RA cohort. Trends in other lipid
      measures (triglycerides (TGs) and high-density lipoprotein cholesterol (HDL))
      were similar in RA and non-RA cohorts during the 5 years before and 5 years after
      the RA incidence/index date. During the 5 years before the RA incidence/index
      date, the proportion of patients with RA with elevated TC or LDL measures, but
      not with abnormal HDL and TG measures, significantly decreased compared with non
      RA subjects. Lipid-lowering drugs (statins in particular) were less often
      prescribed to patients with RA than to non-RA subjects (34% vs 41%; p=0.02).
      CONCLUSION: TC and LDL levels and the prevalence of abnormal TC or LDL measures
      decreased significantly during the 5 years before the RA incidence/index date in
      patients with RA as compared with the non-RA cohort. These trends in lipid
      profile in RA are unlikely to be solely due to lipid-lowering treatment.

PMID- 19854709
TI  - iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a
      novel inflammatory biomarker in autoimmune diseases.
AB  - OBJECTIVE: To identify a novel serum biomarker of disease activity in
      inflammatory autoimmune disorders. METHODS: Sera obtained from rheumatoid
      arthritis (RA) patients before and after anti-TNF therapy were analysed by iTRAQ
      (isobaric tags for relative and absolute quantitation) quantitative proteomic
      analysis and further validated by ELISA. RESULTS: Of 326 proteins identified by
      proteomic analysis, increased serum levels of leucine-rich alpha-2 glycoprotein
      (LRG) was identified in RA patients before therapy. Serum LRG concentrations were
      significantly elevated in RA patients compared with healthy controls and
      decreased after anti-TNF therapy. Furthermore, serum LRG concentrations
      correlated with disease activity in RA and Crohn's disease (CD). Interestingly,
      in a subpopulation of patients with active CD and normal C-reactive protein
      levels, serum LRG concentrations were elevated. CONCLUSIONS: LRG represents a
      novel serum biomarker for monitoring disease activity during therapy in
      autoimmune patients, particularly useful in patients with active disease but
      normal CRP levels.

PMID- 19854710
TI  - Hepatoprotective effect of tumour necrosis factor alpha blockade in psoriatic
      arthritis: a cross-sectional study.
AB  - OBJECTIVE: To evaluate the impact of tumour necrosis factor alpha (TNFalpha)
      blockers on the presence of liver fibrosis in patients with rheumatoid arthritis
      (RA) and psoriatic arthritis (PsA) treated with methotrexate (MTX). METHODS:
      Participants were consecutive patients with RA and PsA who had undergone MTX
      treatment for at least 1 year + or - TNF blockade for over 6 months. Liver
      fibrosis was assessed using non-invasive transient elastography (FibroScan).
      Regression models were used to compare FibroScan values of patients with RA and
      patients with PsA receiving TNFalpha blockers with those who were not. RESULTS:
      FibroScan assessments were performed on 51 patients with RA and 43 patients with
      PsA. Compared to patients with RA, those with PsA were predominantly young men,
      received lower cumulative dosages of MTX and exhibited a higher incidence of
      liver steatosis and hyperlipidaemia. An abnormal result was observed in 7.1% of
      the anti-TNFalpha-naive and in 13% of the anti-TNFalpha-treated patients in the
      RA group and in 30% of the anti-TNFalpha-naive and 4.3% of the anti-TNFalpha
      treated patients in the PsA group (OR=0.11, 95% CI 0.02 to 0.98). Results of the
      PsA group were robust when adjusted for baseline characteristics. CONCLUSION: The
      results suggest a protective effect of TNFalpha inhibitors against the
      development of liver fibrosis in patients with PsA.

PMID- 19854711
TI  - Blood dendritic cells in systemic lupus erythematosus exhibit altered activation
      state and chemokine receptor function.
AB  - BACKGROUND: Dendritic cells (DCs) have a pivotal role in the pathogenesis of
      systemic lupus erythematosus (SLE). Reduced numbers of blood DCs and the
      accumulation of DCs at inflammatory sites have been observed in SLE. One crucial
      feature of DCs is their ability to migrate. OBJECTIVE: To analyse the
      maturation/activation state and the migratory capacity of different DC precursor
      subsets in SLE to further elucidate their role in autoimmunity. METHODS:
      Plasmacytoid DCs (pDCs), myeloid DCs (mDCs) and monocytes from patients with SLE,
      healthy volunteers and healthy volunteers immunised with tetanus/diphtheria were
      examined by flow cytometry for expression of subset-specific antigens (BDCA-2,
      CD11c, CD14, HLA-DR), activation/maturation markers (CD83, CD86, CD40, BLyS) and
      chemokine receptors (CCR1, CCR5, CCR7, ChemR23). Additionally, migratory capacity
      to chemokine receptors was investigated in vitro using the chemokines RANTES,
      CCL19 and chemerin. RESULTS: SLE monocytes and mDCs had higher CD86 and B
      lymphocyte stimulatory factor (BLyS) expression levels. ChemR23 expression was
      lower in SLE pDCs and mDCs. Basal and CCL19-specific migration levels were higher
      in SLE pDCs. Altered DC function in SLE had no correlative changes in chemokine
      receptor expression, whereas immunisation-induced blood DC migration patterns in
      healthy donors were accompanied by changes in chemokine receptor expression.
      CONCLUSIONS: The phenotypic and migratory disturbances observed in SLE blood DCs
      could result in altered distribution of DCs in peripheral tissues, contributing
      to dysregulated immune responses and autoimmunity.

PMID- 19854712
TI  - Increase in age at onset of giant cell arteritis: a population-based study.

PMID- 19854713
TI  - Effects of dehydroepiandrosterone on fatigue and well-being in women with
      quiescent systemic lupus erythematosus: a randomised controlled trial.
AB  - OBJECTIVE: Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and
      reduced well-being. Both are major problems in patients with systemic lupus
      erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are
      common in SLE. The present work investigates the effects of DHEA administration
      on fatigue, well-being and functioning in women with inactive SLE. METHODS: In a
      double-blind, randomised, placebo-controlled study, 60 female patients with
      inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were
      general fatigue, depressive mood, mental well-being and physical functioning.
      Assessments were made before treatment, after 3, 6 and 12 months on medication,
      and 6 months after cessation of treatment. RESULTS: Patients from the DHEA and
      placebo group improved on general fatigue (p<0.001) and mental well-being
      (p=0.04). There was no differential effect of DHEA. The belief that DHEA had been
      used was a stronger predictor for improvement of general fatigue than the actual
      use of DHEA (p=0.04). CONCLUSIONS: The trial does not indicate an effect of daily
      200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not
      recommended in unselected female patients with quiescent SLE. Clinical Trials
      Registration Number NCT00391924.

PMID- 19854714
TI  - HLA-DRB1*0901 lowers anti-cyclic citrullinated peptide antibody levels in
      Japanese patients with rheumatoid arthritis.

PMID- 19854716
TI  - New insights into the experience of fatigue among patients with rheumatoid
      arthritis: a qualitative study.
AB  - OBJECTIVES: Patients with rheumatoid arthritis (RA) commonly experience fatigue.
      The aim of this study was to gain further insight into the experience of fatigue
      in RA. METHODS: Participants were 31 outpatients with RA of Medical Spectrum
      Twente, Enschede, The Netherlands, with all levels of fatigue. In-depth
      structured interviews on the patients' experience of fatigue were conducted and
      analysed using a bottom-up coding scheme, meaning that answers of patients were
      summarised and categorised. RESULTS: Patients' mean fatigue severity score was 50
      (visual analogue scale (VAS); theoretical range 0-100). Interviews showed
      interindividual differences in the experience and impact of fatigue. Different
      patterns in emotions, consequences and management of fatigue were found.
      Especially younger women with multiple daily roles seemed to be vulnerable to the
      negative impact of RA fatigue. Patients also reported positive aspects of
      fatigue. Moreover, varying forms of fatigue were described. CONCLUSIONS: Results
      point to the existence of differences in fatigue experience according to gender,
      age and daily roles. This finding indicates a need for targeting advice and
      interventions to the individual situation of a patient. Furthermore, the positive
      aspects patients reported about their fatigue could facilitate an approach that
      is focused on remaining opportunities and not just on restrictions.

PMID- 19854715
TI  - Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated
      with anti-TNF therapy: results from the British Society for Rheumatology
      Biologics Register (BSRBR).
AB  - BACKGROUND: The risk of tuberculosis (TB) in patients with rheumatoid arthritis
      (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF)
      therapy, with a proposed differential risk between the anti-TNF drugs etanercept
      (ETA), infliximab (INF) and adalimumab (ADA). OBJECTIVE: To compare directly the
      risk between drugs, to explore time to event, site of infection and the role of
      ethnicity. METHODS: Data from the British Society for Rheumatology Biologics
      Register (BSRBR), a national prospective observational study, were used to
      compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504
      ADA) and 3232 patients with active RA treated with traditional disease-modifying
      antirheumatic drugs. RESULTS: To April 2008, 40 cases of TB were reported, all in
      the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA
      (144 events/100,000 person-years) and INF (136/100,000 person-years) than for ETA
      (39/100,000 person-years). After adjustment, the incidence rate ratio compared
      with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to
      12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared
      with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping
      treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated.
      Patients of non-white ethnicity had a sixfold increased risk of TB compared with
      white patients treated with anti-TNF therapy. CONCLUSION: The rate of TB in
      patients with RA treated with anti-TNF therapy was three- to fourfold higher in
      patients receiving INF and ADA than in those receiving ETA.

PMID- 19854717
TI  - The chromosome 16q region associated with ankylosing spondylitis includes the
      candidate gene tumour necrosis factor receptor type 1-associated death domain
      (TRADD).
AB  - OBJECTIVE: To replicate and refine the reported association of ankylosing
      spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs)
      on chromosome 16q22.1. METHODS: Firstly, 730 independent UK patients with AS were
      genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879
      previously typed historic disease controls. Secondly, the two data sets were
      combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and
      rs6979, were analysed in 1604 cases and 1020 controls. RESULTS: The association
      of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a
      trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to
      1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31
      (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768
      and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002,
      OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72),
      respectively, were identified. CONCLUSIONS: The region on chromosome 16 that has
      been replicated in the present work is interesting as the highly plausible
      candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death
      domain (TRADD), is located between rs9033 and rs868213. It will require
      additional work to identify the primary genetic association(s) with AS.

PMID- 19854718
TI  - Inhalational anesthesia: basic pharmacology, end organ effects, and applications
      in the treatment of status asthmaticus.
AB  - The potent inhalational anesthetic agents are used on a daily basis to provide
      intraoperative anesthesia. Given their beneficial effects on airway tone and
      reactivity, they also have a role in the treatment of status asthmaticus that is
      refractory to standard therapy. Although generally not of clinical significance,
      these agents can affect various physiological functions. The potent inhalational
      anesthetic agents decrease mean arterial pressure and myocardial contractility.
      The decrease in mean arterial pressure reduces renal and hepatic blood flow.
      Secondary effects on end-organ function may result from the metabolism of these
      agents and the release of inorganic fluoride. The following article reviews the
      history of inhalational anesthesia, the physical structure of the inhalational
      anesthetic agents, their end-organ effects, reports of their use for the
      treatment of refractory status asthmaticus in the intensive care unit (ICU)
      patient, and special considerations for their administration in this setting
      including equipment for their delivery, scavenging, and monitoring.

PMID- 19854719
TI  - Developing a spatial analogue of the reliable digit span.
AB  - It is recommended that performance validity be assessed in all neuropsychological
      cases involving external incentive. The present study sought to develop an
      embedded performance validity measure based on the Spatial Span task of the
      Wechsler Memory Scale-III in a sample of litigating persistent postconcussion
      complainants. The Reliable Spatial Span (RSS) calculation had specificity,
      sensitivity, and predictive power values within the range of other embedded
      measures. This finding suggests that RSS is able to distinguish between
      persistent postconcussion complainants demonstrating valid and invalid
      performance. Other calculations involving Spatial Span scores had lower
      classification accuracy. Reliable Digit Span (RDS) classification accuracy within
      the present sample was lower than that of previous research, as well as of RSS.
      Potential reasons for lack of RDS replication are discussed, along with the
      potential use of RSS as an embedded validity performance indicator.

PMID- 19854720
TI  - Photosynthetic acclimation is important for post-submergence recovery of
      photosynthesis and growth in two riparian species.
AB  - BACKGROUND AND AIMS: Concomitant increases in O(2) and irradiance upon de
      submergence can cause photoinhibition and photo-oxidative damage to the
      photosynthetic apparatus of plants. As energy and carbohydrate supply from
      photosynthesis is needed for growth, it was hypothesized that post-submergence
      growth recovery may require efficient photosynthetic acclimation to increased
      O(2) and irradiance to minimize photo-oxidative damage. The hypothesis was tested
      in two flood-tolerant species: a C(3) herb, Alternanthera philoxeroides; and a
      C(4) grass, Hemarthria altissima. The impact of low O(2) and low light, typical
      conditions in turbid floodwater, on post-submergence recovery was assessed by
      different flooding treatments combined with shading. METHODS: Experiments were
      conducted during 30 d of flooding (waterlogging or submergence) with or without
      shading and subsequent recovery of 20 d under growth conditions. Changes in dry
      mass, number of branches/tillers, and length of the longest internodes and main
      stems were recorded to characterize growth responses. Photosynthetic parameters
      (photosystem II efficiency and non-photochemical quenching) were determined in
      mature leaves based on chlorophyll a fluorescence measurements. KEY RESULTS: In
      both species growth and photosynthesis recovered after the end of the submergence
      treatment, with recovery of photosynthesis (starting shortly after de
      submergence) preceding recovery of growth (pronounced on days 40-50). The
      effective quantum yield of photosystem II and non-photochemical quenching were
      diminished during submergence but rapidly increased upon de-submergence. Similar
      changes were found in all shaded plants, with or without flooding. Submerged
      plants did not suffer from photoinhibition throughout the recovery period
      although their growth recovery was retarded. CONCLUSIONS: After sudden de
      submergence the C(3) plant A. philoxeroides and the C(4) plant H. altissima were
      both able to maintain the functionality of the photosynthetic apparatus through
      rapid acclimation to changing O(2) and light conditions. The ability for
      photosynthetic acclimation may be essential for adaptation to wetland habitats in
      which water levels fluctuate.

PMID- 19854721
TI  - Reversibility of capillary density after discontinuation of bevacizumab
      treatment.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) inhibition is known to
      decrease capillary density. Decreased capillary density may be the basis for VEGF
      inhibitor-related side-effects. We investigated whether the effects of
      bevacizumab on capillary density are reversible. PATIENTS AND METHODS: Capillary
      density, assessed by sidestream dark field imaging of the mucosal surface of the
      lip, was measured at baseline, after 6 weeks of bevacizumab treatment and >3
      months after discontinuation. Additional measurements included blood pressure
      (BP) measurements, flow-mediated dilation (FMD), nitroglycerin-mediated dilation
      (NMD) and aortic pulse wave velocity (PWV). RESULTS: Fourteen patients were
      included. Seven patients completed measurements at all three predefined time
      points. Capillary density significantly decreased after 6 weeks of bevacizumab
      treatment and was reversible after discontinuation of bevacizumab (P = 0.00001
      using a general linear model repeated measures test). BP, FMD and NMD remained
      unchanged. Mean PWV increased after 6 weeks of treatment (P = 0.027) and
      decreased after bevacizumab discontinuation. Among the six patients with the best
      response were the three patients showing the clearest decrease in capillary
      density after 6 weeks of bevacizumab treatment. CONCLUSIONS: Bevacizumab-induced
      decrease in capillary density is reversible. Noninvasive assessment of capillary
      density during treatment with antiangiogenic drugs may be useful as a marker of
      treatment efficacy.

PMID- 19854722
TI  - A phase II trial of capecitabine and docetaxel followed by 5
      fluorouracil/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women
      with stage II/III breast cancer.
AB  - BACKGROUND: Capecitabine (X) and docetaxel (T) have demonstrated a synergistic
      effect in preclinical models and a survival benefit in metastatic breast cancer.
      This study's purpose was to determine the efficacy of X and T followed by 5
      fluorouracil/epirubicin/cyclophosphamide (FEC) in the preoperative setting.
      PATIENTS AND METHODS: Patients with stage II/III breast cancer received four
      cycles of XT (capecitabine 1650 mg/m(2) on days 1-14 and docetaxel 60 mg/m(2) on
      day 8 every 3 weeks), followed by four cycles of FEC (5-fluorouracil 500 mg/m(2),
      epirubicin 90 mg/m(2), and cyclophosphamide 500 mg/m(2) on day 1 every 3 weeks).
      Primary end points were the pathological complete response (pCR) rate and adverse
      drug reactions. RESULTS: Seventy-four patients were enrolled and 71 patients were
      assessable for clinical and pathological responses. The overall response rate was
      91.5%. The pCR rate was 14.1% (10 of 71). Grade 3/4 neutropenia was observed in
      32.4% of patients. The most common grade 3/4 non-hematologic adverse event was
      hand-foot syndrome, observed in 11.3% of patients. With 29 months median follow
      up, 2-year disease-free survival was estimated 85% for all patients. CONCLUSION:
      These data indicate that the sequential combination of XT followed by FEC is a
      well-tolerated, effective neoadjuvant treatment of stage II/III breast cancer.

PMID- 19854723
TI  - Acute and chronic renal artery stenosis.

PMID- 19854724
TI  - Collaboration between cardiac computed tomography and echocardiography in complex
      anomalies.

PMID- 19854725
TI  - Sixty-four-slice computed tomography for the detection of multiple intra-thoracic
      thrombi in Trousseau syndrome.

PMID- 19854726
TI  - Severe ventricular arrhythmias in a patient with cardiac sarcoidosis: insights
      from MRI and PET imaging and importance of early corticosteroid therapy.

PMID- 19854727
TI  - Stent thrombosis: who's guilty?

PMID- 19854728
TI  - Correlation of inhibition of platelet aggregation after clopidogrel with post
      discharge bleeding events: assessment by different bleeding classifications.
AB  - AIMS: To correlate inhibition of platelet aggregation (IPA) with bleeding events
      assessed by TIMI, GUSTO, and BleedScore scales in a large cohort of patients with
      coronary artery disease (CAD) and ischaemic stroke (IS) treated with chronic low
      dose aspirin plus clopidogrel. Data from recent trials and registries suggest a
      link between increased risk of bleeding and cardiovascular mortality. However,
      the potential association of bleeding risk and IPA is not established. It may
      play a critical role for the safety of more aggressive platelet inhibition or/and
      individual tailoring of antiplatelet strategies. METHODS AND RESULTS: Secondary
      post hoc analyses of 5 microM ADP-induced IPA and bleeding complications assessed
      by TIMI, GUSTO, and BleedScore scales in a combined data set consisting of
      patients with documented CAD (n = 246) and previous IS (n = 117). Demographic
      characteristics differ substantially depending on the underlying vascular
      disease; however, IPA and bleeding risks were similar between CAD and IS. All
      three bleeding scales adequately captured serious haemorrhagic events, where the
      TIMI scale was the most exclusive, whereas BleedScore was the most inclusive.
      Over half of all patients experienced superficial event(s), most commonly
      occurring during two to three distinct bleeding episodes. There was no
      correlation between IPA and duration of antiplatelet therapy. Inhibition of
      platelet aggregation >50% strongly correlates with minor (r(2) = 0.58, P < 0.001;
      c-statistic = 0.92), but not severe (r(2) = 0.11, P = 0.038; c-statistic = 0.57),
      bleeding events. CONCLUSION: Chronic oral combination antiplatelet regimens are
      associated with a very high (56.5-60.7%) prevalence of superficial bleeding
      episodes, which are grossly underestimated in trials and registries. The role of
      such frequent mild complications for the overall benefit of antiplatelet therapy
      is entirely unknown, as is their effect on compliance. Although IPA is well
      suited for defining the risk of minor complications, prediction of more severe
      bleeding events may be challenging.

PMID- 19854729
TI  - Predictors of sudden cardiac death change with time after myocardial infarction:
      results from the VALIANT trial.
AB  - AIMS: To determine whether predictors of sudden cardiac death (SCD) vary with
      time after myocardial infarction (MI). METHODS AND RESULTS: We analysed 11 256
      patients enrolled in VALIANT. Landmark analysis and Cox proportional hazards
      modelling were used to predict SCD during hospitalization, from discharge to 30
      days, 30 days to 6 months, and 6 months to 3 years. The cumulative incidence of
      SCD was 8.6% (n = 965). Initially, higher baseline heart rate [HR 1.20 per 10
      b.p.m. (95% CI 1.06-1.37)] and impaired baseline creatinine clearance [HR 0.82
      per 10 mL/min (95% CI 0.74-0.91)] were stronger predictors of SCD. With long-term
      follow-up, prior MI [HR 1.71 (95% CI 1.39-2.10)], initial left ventricular
      ejection fraction <40% [HR 0.67 per 10% (95% CI 0.58-0.78)], and recurrent
      cardiovascular events [HR 1.47 for rehospitalization (95% CI 1.17-1.86)] were
      more robust risk stratifiers for SCD. Atrial fibrillation post-MI was associated
      with an increased risk of SCD over the entire follow-up period. As time passed,
      the associations between baseline clinical characteristics and SCD decreased and
      time-updated assessments became more important. CONCLUSION: Predictors of SCD
      change with time after MI. Future studies of risk stratification for SCD should
      account for changes in these factors with time after MI.

PMID- 19854731
TI  - N-terminal pro-B-type natriuretic peptide is an independent predictor of
      cardiovascular morbidity and mortality in the general population.
AB  - AIMS: Natriuretic peptides including N-terminal pro-B-type natriuretic peptide
      (NT-proBNP) are established biomarkers in heart failure. However, their
      prognostic value in the general population is less well established. The purpose
      of our study was to investigate the prognostic properties of NT-proBNP for death
      and cardiovascular (CV) events in the general population. METHODS AND RESULTS: In
      the population-based Prevention of Renal and Vascular End-stage Disease (PREVEND)
      study, 8383 subjects were prospectively followed for a median period of 7.5
      years. There were 4181 (49.9%) males and 4202 (50.1%) females, mean age was 49.3
      +/- 12.7 years (range 28-75). Median NT-proBNP at baseline was 37.7 pg/mL (IQR
      16.8-73.8). All-cause death occurred in 437 (5.2%) subjects and there were 557
      (6.6%) CV events. Higher levels of plasma NT-proBNP were related to higher event
      rates. When adjusted for age, gender, and other relevant covariates, each
      doubling of NT-proBNP remained significantly associated with a 22% increased risk
      for all-cause mortality (P < 0.001) and a 16% increased risk of CV events (P <
      0.001). CONCLUSION: In this large community-based cohort, plasma NT-proBNP was a
      strong predictor of death and a wide range of CV events.

PMID- 19854730
TI  - Do systemic risk factors impact invasive findings from virtual histology?
      Insights from the international virtual histology registry.
AB  - AIMS: Cardiovascular risk factors such as elevated serum lipid levels are
      important in the development of coronary atherosclerosis. Radiofrequency (RF)
      analysis of intravascular ultrasound [IVUS, Virtual histology (VH)] offers a
      unique tool to study the composition of coronary atherosclerotic plaque in vivo.
      We used data from the multicentre VH registry to assess the association between
      cardiovascular risk factors and coronary plaque volume and composition. METHODS
      AND RESULTS: Between August 2004 and July 2006, 990 patients in 42 centres were
      enrolled in a prospective, multicentre, non-randomized global VH registry.
      Coronary artery imaging was performed by conventional IVUS and RF-IVUS. The four
      RF-IVUS plaque components [dense calcium (DC), necrotic core (NC), fibrous (F)
      tissue, and fibro fatty (FF)] were analysed in every recorded frame. The results
      were expressed as mean cross-sectional areas, absolute volume, and percentage of
      total plaque volume. Risk factor assessment included evaluation of family history
      of previous myocardial infarction (MI), past or current smoking, diabetes
      mellitus, hypertension, and the laboratory measurements. Patients with diabetes
      had an increased relative proportion of NC (6.47 +/- 0.28 vs. 5.86 +/- 0.14%, P =
      0.037) and DC (4.58 +/- 0.27 vs. 3.90 +/- 0.14%, P = 0.017), and patients with
      hypertension had an increased relative proportion of FF, DC (4.35 +/- 0.16 vs.
      3.57 +/- 0.17%, P = 0.02) and NC (6.24 +/- 0.17 vs. 5.60 +/- 0.19%, P = 0.01).
      Compared with patients with LDL-C <100 mg/dL, patients with LDL-C >160 mg/dL had
      higher plaque volume (342.1 +/- 26.2 vs. 318.6 +/- 10.7 mm(3)). Linear regression
      analysis showed a correlation between the level of HDL-C and F (r = -0.149, P <
      0.01), FF (r = -0.106, P < 0.01), and NC (r = -0.90, P < 0.05). The level of LDL
      correlated with F (r = 0.110, P < 0.01). Patients with prior MI have an increased
      percentage of F (30.03 +/- 0.59 vs. 28.20 +/- 0.37%, P = 0.009). Smoking had no
      relevant effect on plaque composition. Treatment with acetylsalicylacid and
      statins reduced FF with altering plaque volume. CONCLUSION: Radiofrequency-IVUS
      detects marked differences in coronary plaque composition related to the risk
      factor profile with particular focus on lipid levels. Greater amounts of NC were
      associated with diabetes, hypertension, MI, and low HDL-C. The effects of
      treatment of changes related to plaque composition are underway.

PMID- 19854732
TI  - C-reactive protein improves risk prediction in patients with acute coronary
      syndrome, or does it?

PMID- 19854735
TI  - Helicobacter pylori: an intruder involved in conspiring glaucomatous neuropathy.

PMID- 19854733
TI  - Long-term visual and anatomical outcomes following anti-VEGF monotherapy for
      retinal angiomatous proliferation.
AB  - AIM: To study the long-term visual and anatomical outcomes of antivascular
      endothelial growth factor (VEGF) monotherapy for the treatment of patients with
      retinal angiomatous proliferation (RAP). METHODS: Retrospective review of
      patients who were diagnosed as having AMD and RAP lesions, and who received anti
      VEGF injections as the only mode of therapy. RESULTS: 20 eyes (15 patients; nine
      women, six men) with RAP lesions treated by anti-VEGF were encountered. The mean
      patient age was 85.8 years (SD+/-4.54). Nine eyes were treated with intravitreal
      ranibizumab alone, eight eyes were treated with bevacizumab alone, and three eyes
      received both drugs. At 1, 3 and 6 months' follow-up the median VA had improved
      from baseline (20/72) to 20/52 (range: 20/25 to 20/400), 20/45 (range 20/20 to
      20/400), and 20/56 (range 20/20 to 20/400), respectively, (p>0.001, p=0.001 and
      p=0.05, respectively). At the 24-month follow-up, the improvement in VA, defined
      as a halving of the visual angle, occurred in 37.5% of the cases. CONCLUSIONS:
      Anti-VEGF monotherapy represents a useful treatment option for RAP, with stable
      or improved visual acuity in 62.5% of patients at 2 years. 25% of eyes required
      only a single injection, but in most cases (75%) repeated treatments were
      required, highlighting the need for long term follow-up. Although, in this small
      study, the results for visual improvement were not statistically significant
      beyond 3 months, our findings warrant further large-scale investigation.

PMID- 19854736
TI  - Electric eyes: Wirtz iontophoresis electrodes.

PMID- 19854737
TI  - Management of acquired nasolacrimal duct obstruction: external and endonasal
      dacryocystorhinostomy. Is there a third way?

PMID- 19854738
TI  - Glaucoma and Helicobacter pylori infection: correlations and controversies.
AB  - A possible association between Helicobacter pylori infection and eye diseases,
      including Sjogren syndrome, blepharitis, central serous chorioretinopathy and
      uveitis, has been proposed. Glaucoma is the second leading cause of blindness in
      the world, after cataracts, and the leading cause of irreversible blindness, but
      many aspects of its pathogenesis remain unknown. H pylori infection may influence
      the pathophysiology of glaucoma by releasing various proinflammatory and
      vasoactive substances, as well as by influencing the apoptotic process,
      parameters that may also exert their own effects in the induction and/or
      progression of glaucomatous neuropathy. It is difficult to understand how H
      pylori infection can be linked to such varied pathologies. Systemic H pylori
      induced oxidative damage may be the mechanism which links oxidative stress, H
      pylori infection and the damage to the trabecular meshwork and optical nerve head
      that results in glaucoma.

PMID- 19854740
TI  - Intraobserver variability of confocal scanning laser ophthalmoscopy with and
      without stereo photographs.

PMID- 19854741
TI  - Efficacy of infliximab therapy in two patients with refractory Vogt-Koyanagi
      Harada disease.

PMID- 19854739
TI  - Cataract surgery and primary intraocular lens implantation in children < or = 2
      years old in the UK and Ireland: finding of national surveys.
AB  - BACKGROUND: Current patterns of practice relating to primary intraocular lens
      (IOL) implantation in children < or =2 years old in the UK and Ireland are
      investigated. METHODS: National postal questionnaire surveys of consultant
      ophthalmologists in the UK and Ireland. RESULTS: 76% of 928 surveyed
      ophthalmologists replied. 47 (7%) of the respondents operated on children aged <
      or =2 with cataract. 41 (87%) of respondents performed primary IOL implantation,
      but 25% would not implant an IOL in a child under 1 year old. 88% of surgeons
      used limbal wounds, 80% manual capsulotomies, 98% posterior capsulotomies and
      100% hydrophobic acrylic lenses. The SRK/T formula was most commonly used (70%).
      Exclusion criteria for primary IOL implantation varied considerably and included
      microphthalmos (64% of respondents), anterior and posterior segment anomalies
      (53%, 58%), and glaucoma (19%). DISCUSSION: Primary IOL implantation in children
      < or =2 has been widely adopted in the UK and Ireland. There is concordance of
      practice with regards to surgical technique and choice of IOL model. However,
      there is some variation in eligibility criteria for primary IOLs: this may
      reflect a lack of consensus on which children are most likely to benefit. Thus,
      there is a need for systematic studies of the outcomes of primary IOL
      implantation in younger children.

PMID- 19854742
TI  - Episcleritis following keratorefractive surgery.

PMID- 19854743
TI  - Ozone and cause-specific cardiorespiratory morbidity and mortality.
AB  - BACKGROUND: Health effects of ozone have been observed in numerous studies.
      However, analyses of more cause-specific morbidity or mortality outcomes have
      rarely been performed. A study was undertaken to determine the short-term
      associations of ozone with cause-specific cardiorespiratory mortality and
      morbidity by age groups. METHODS: Daily levels of ozone were measured at a
      background measurement station in 1998-2004 in Helsinki, Finland. All analyses
      were a priori restricted to the warm season. Daily cause-specific
      cardiorespiratory mortality and hospital admissions were studied in elderly
      people (> or =65 years) and adults (15-64 years) and associations between ozone
      and asthma emergency room visits in children (<15 years) were analysed. All
      models were adjusted for PM(2.5) and Poisson regression was used for the
      analyses. RESULTS: There was a positive association between ozone and admissions
      for asthma-chronic obstructive pulmonary disease (COPD) in elderly people (9.6%;
      95% CI 2.0% to 17.8% at 0-day lag for 25 microg/m(3) increase in ozone).
      Consistent associations were also found between ozone and asthma emergency room
      visits in children (12.6%; 95% CI 0.8% to 25.1%, 0-day lag). There was a
      suggestion of an association between ozone and admissions for arrhythmia among
      elderly people (6.4%; 95% CI 0.63% to 12.5%, 1-day lag), which was slightly
      confounded by PM(2.5). CONCLUSIONS: Positive associations were found for ambient
      ozone with asthma visits among children and with pooled asthma/COPD admissions
      among elderly people. The evidence for a positive association between ozone and
      cardiovascular health was weaker.

PMID- 19854744
TI  - "My story is like a goat tied to a hook." Views from a marginalized tribal group
      in Kerala (India) on the consequences of falling ill: a participatory poverty and
      health assessment.
AB  - BACKGROUND: Indigenous populations tend to have the poorest health outcomes
      worldwide and they have limited opportunities to present their own perspectives
      of their situation and shape priorities in research and policy. This study aims
      to explain low healthcare utilisation rates and opportunities to cope with
      illness among a deprived indigenous group - based on their own experiences and
      views. METHODS: A participatory poverty and health assessment (PPHA) was
      conducted among the Paniyas, a previously enslaved tribal population of South
      India in a Gram Panchayat in Kerala, India in 2008. Purposive sampling was used
      to select five Paniya colonies, involving 66 households. RESULTS: There were four
      key findings. First, Paniyas' perception that the quality of the public
      healthcare system is poor leads them to seek suboptimal care or deters them from
      using services. Second, there are significant costs of care unrelated to service
      use or purchase of medicines, such as travel costs, which the Paniyas lack the
      ability to pay. Third, illness can lead to loss of productive opportunities among
      those who fall ill and those who provide informal care. Fourth, the Paniyas lack
      a 'range' of coping strategies as they are wage labourers without diverse sources
      of income. They rely on a single strategy: borrowing from outside their
      community, often from landowners and employers, to whom they become indebted with
      their labour. CONCLUSIONS: Improving the capacity of tribal populations to
      present their own perspectives is likely to lead to more effective tribal
      development policies and consequently better health.

PMID- 19854745
TI  - Comorbid chronic diseases, discordant impact on mortality in older people: a 14
      year longitudinal population study.
AB  - OBJECTIVES: To determine the impact of comorbid chronic diseases on mortality in
      older people. DESIGN: Prospective cohort study (1992-2006). Associations between
      numbers of chronic diseases or mutually exclusive comorbid chronic diseases on
      mortality over 14 years, by Cox proportional hazards model adjusting for
      sociodemographic variables or Kaplan-Meier analyses, respectively. SETTING:
      Population based, Australia. PARTICIPANTS: 2087 randomly selected participants
      aged >=65 years old, living in the community or institutions. MAIN RESULTS:
      Participants with 3-4 or >=5 diseases had a 25% (95% CI 1.05 to 1.5, p=0.01) and
      80% (95% CI 1.5 to 2.2, p<0.0001) increased risk of mortality, respectively, by
      comparison with no chronic disease, after adjusting for age, sex and residential
      status. When cardiovascular disease (CVD), mental health problem or diabetes were
      comorbid with arthritis, there was a trend towards increased survival (range 8.2
      9.5 years) by comparison with CVD, mental health problem or diabetes alone
      (survival 5.8-6.9 years). This increase in survival with arthritis as a
      comorbidity was negated when CVD and mental health problems or CVD and diabetes
      were present in disease combinations together. CONCLUSION: Older people with >=3
      chronic diseases have increased risk of mortality, but discordant effects on
      survival depend on specific disease combinations. These results raise the
      hypothesis that patients who have an increased likelihood of opportunity for care
      from their physician are more likely to have comorbid diseases detected and
      managed.

PMID- 19854746
TI  - Socio-economic status, ethnicity and geographical variations in acceptance rates
      for renal replacement therapy in England and Wales: an ecological study.
AB  - BACKGROUND: It is not known to what extent the reported regional variations in
      renal replacement therapy (RRT) acceptance rates in England and Wales are due to
      differences in the socio-demographic characteristics of the population. METHODS:
      The authors calculated age-gender indirectly standardised RRT rates in 2007 for
      Primary Care Trusts (PCT)/Local Health Boards (LHB) in England and Wales and
      Government Office Regions (GOR) in England. Multivariable Poisson regression was
      used to examine the regional variations in the age-gender standardised RRT rates
      before and after adjustment for area deprivation (Townsend index) and the
      proportion of non-white people living in an area. RESULTS: Increasing deprivation
      of PCT/LHB was associated with higher RRT acceptance rates. RRT rates were higher
      in PCTs with a greater proportion of non-white people in England (correlation
      coefficient 0.60, p<0.001) but not in Wales. There were variations in the age
      gender standardised RRT rates between PCT/LHBs in England and Wales. Adjusting
      for deprivation and the proportion of non-white people attenuated the high RRT
      rate ratio observed in London and West Midlands, but the RRT acceptance rate
      ratio (95% CI) remained higher in Wales 1.38 (1.22 to 1.57) and lower in North
      West England 0.82 (0.74 to 0.93) and Yorkshire and Humberside 0.86 (0.77 to
      0.98). CONCLUSIONS: This study highlights that RRT acceptance rates are
      positively associated with social deprivation and the proportion of non-white
      people in a PCT/LHB, but regional variations in RRT acceptance rates still
      persist despite taking these into account. Further study is required to
      understand the extent to which these differences reflect variation in underlying
      need or provision of care.

PMID- 19854748
TI  - Does dissatisfaction with psychosocial work climate predict depressive, anxiety
      and substance abuse disorders? A prospective study of Danish public service
      employees.
AB  - BACKGROUND: The aim of this study was to examine if dissatisfaction with
      psychosocial work climate predicts psychiatrically diagnosed depressive, anxiety
      and substance abuse disorders. METHODS: In Aarhus County, Denmark, 13 423 public
      service employees at 683 workplace units answered a questionnaire survey
      assessing psychosocial work environment. An average workplace unit score of
      overall satisfaction with psychosocial working conditions, rated on a scale from
      0-10 with 10 being most satisfied, was computed and assigned to the individual
      employees at each work unit. Aggregated satisfaction scores were divided into
      three levels, according to the 25-75 percentiles. Data on hospitalisations and
      outpatient treatments for depressive, anxiety and substance abuse disorders was
      obtained from the Danish Central Psychiatric Research Register. HRs and 95% CIs
      were computed for first onset of studied disorders, starting from the baseline
      survey at 1 January 2002 through to 30 April 2008. Risk estimates were adjusted
      for sociodemographic variables. RESULTS: A low satisfaction with psychosocial
      working conditions was associated with an increased risk of any mental health
      disorder, HR(adj) 1.71, 95% CI 1.04 to 2.82. The lower the satisfaction level,
      the higher was the risk of mental health disorders. Moreover, substance abuse
      disorders were more frequent among men dissatisfied with work climate, HR(adj)
      3.53, 95% CI 1.55 to 8.03. CONCLUSION: Working in a dissatisfying psychosocial
      environment increases the risk of subsequent mental health disorders. Randomised,
      controlled intervention trials may help in resolving whether this association is
      causal.

PMID- 19854747
TI  - Socioeconomic status, race and COPD health outcomes.
AB  - BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is a common
      cause of death and disability, little is known about the effects of socioeconomic
      status (SES) and race-ethnicity on health outcomes. METHODS: The aim of this
      study is to determine the independent impacts of SES and race-ethnicity on COPD
      severity status, functional limitations and acute exacerbations of COPD among
      patients with access to healthcare. Data were used from the Function, Living,
      Outcomes and Work cohort study of 1202 Kaiser Permanente Northern California
      Medical Care Plan members with COPD. RESULTS: Lower educational attainment and
      household income were consistently related to greater disease severity, poorer
      lung function and greater physical functional limitations in cross-sectional
      analysis. Black race was associated with greater COPD severity, but these
      differences were no longer apparent after controlling for SES variables and other
      covariates (comorbidities, smoking, body mass index and occupational exposures).
      Lower education and lower income were independently related to a greater
      prospective risk of acute COPD exacerbation (HR 1.5; 95% CI 1.01 to 2.1; and HR
      2.1; 95% CI 1.4 to 3.4, respectively). CONCLUSION: Low SES is a risk factor for a
      broad array of adverse COPD health outcomes. Clinicians and disease management
      programs should consider SES as a key patient-level marker of risk for poor
      outcomes.

PMID- 19854749
TI  - Polypharmacy and its correlates in village health clinics across 10 provinces of
      Western China.
AB  - BACKGROUND: Polypharmacy represents a growing public health concern for its
      associations with drug-related adverse events, poor adherence, medication errors
      and increased healthcare costs. AIM: To assess the occurrence of polypharmacy
      prescribing and to identify the correlates in terms of doctors and patients
      characteristics in rural Western China. METHODS: 20,125 prescriptions were
      collected from 680 primary health clinics in villages from 40 counties in 10
      provinces of Western China. Two outcome variables are used in the analysis:
      number of drug items prescribed and use of five or more drugs (polypharmacy). A
      multilevel Poisson regression model and a multilevel logistic regression model
      were employed to examine the socio-economic, demographic determinants of the
      above two outcome variables, respectively. RESULTS: The average drug number per
      prescription was 2.36, and the percentage of polypharmacy was 5.8%. The odds for
      polypharmacy were higher for village doctors with a heavier workload than those
      with less workload (OR=1.70; 95% CI 1.26 to 2.29). Patients with injections
      prescribed had higher odds for polypharmacy than patients without injections
      (OR=4.61; 95% CI 3.93 to 5.42). Village doctor's workload, subsidy for doctors
      from government and injection in prescriptions, patient's age and gender were
      also significant predictors of number of drug items prescribed in the studied
      areas. CONCLUSIONS: Polypharmacy seems to be associated with the village doctors'
      and patients' background and government policy. Intervention studies are needed
      to promote rational use of drugs in rural China.

PMID- 19854750
TI  - The importance of community education for individual mortality: a fixed-effects
      analysis of longitudinal multilevel data on 1.7 million Norwegian women and men.
AB  - BACKGROUND: Earlier investigations have shown mortality effects of community
      socio-economic resources. However, the sex differences have not been clear, and
      the estimates may well have been biased because of inadequate control for
      community factors affecting both the socio-economic resources and mortality. The
      objective of this study was to see whether any effects appeared when time
      invariant community characteristics were controlled by including community
      dummies (fixed effects) and whether there were any differences between women and
      men. METHODS: Discrete-time hazard models for all-cause mortality were estimated
      for 1981-2002 for all Norwegians aged 60-89, using register data. There were 730
      000 deaths among 1.7 million people observed during 19 million person-years.
      Average education was measured for 433 municipalities for each of the 22 years.
      RESULTS: According to the simplest models, a high average education in the
      municipality is associated with increased mortality. Control for population size
      (time-averaged) reversed the effects. Inclusion of municipality dummies instead
      of population size, to control also for additional unobserved time-invariant
      municipality characteristics, gave very different results: the effects were even
      stronger for men, while those for women were no longer significant. The results
      were quite robust to alternative specifications, including the use of a lagged
      average-education variable. CONCLUSION: The study supports the idea that
      community socio-economic resources may affect mortality and suggests that sex
      differentials may deserve more attention. It also illustrates the importance of
      controlling for time-invariant community factors. Unless these can be easily
      measured, in future investigations one may consider establishing longitudinal
      data and using a fixed-effects approach such as that used here.

PMID- 19854752
TI  - Job insecurity and the use of antidepressant medication among Danish employees
      with and without a history of prolonged unemployment: a 3.5-year follow-up study.
AB  - BACKGROUND: A study was undertaken to investigate whether job insecurity predicts
      incident use of antidepressant medication and whether the association is modified
      by a history of prolonged unemployment. METHODS: A prospective follow-up study
      was performed in 5142 Danish employees, including 632 employees with and 4510
      without a history of prolonged unemployment. Participants were drawn from a
      random 10% sample of the Danish population. Survey data on job insecurity were
      linked with register data on history of unemployment and dispensing of
      antidepressant medication between June 2000 and December 2003 retrieved from the
      Danish Medicinal Product Statistics. Respondents with major depression at
      baseline or antidepressant use in the 5 years preceding baseline were excluded.
      RESULTS: Job insecurity predicted use of antidepressants after adjustment for
      sex, age, cohabitation, socioeconomic position and alcohol consumption (OR 1.43,
      95% CI 1.09 to 1.88). The effect was attenuated after further adjustment for
      baseline depressive symptoms (OR 1.15, 95% CI 0.87 to 1.52). A history of
      prolonged unemployment predicted use of antidepressants in both models (OR 1.62,
      95% CI 1.14 to 2.30 and OR 1.49, 95% CI 1.04 to 2.13, respectively) Compared with
      participants with neither job insecurity nor unemployment history, the OR for the
      joint effect of job insecurity and history of prolonged unemployment was
      substantially higher (OR 1.79, 95% CI 1.15 to 2.79) than the OR for job
      insecurity (OR 1.02) and unemployment history (OR 1.10) alone in the fully
      adjusted model. CONCLUSION: Job insecurity predicts incident use of
      antidepressants among Danish employees with a history of prolonged unemployment.

PMID- 19854751
TI  - Verbal autopsy can consistently measure AIDS mortality: a validation study in
      Tanzania and Zimbabwe.
AB  - BACKGROUND: Verbal autopsy is currently the only option for obtaining cause of
      death information in most populations with a widespread HIV/AIDS epidemic.
      METHODS: With the use of a data-driven algorithm, a set of criteria for
      classifying AIDS mortality was trained. Data from two longitudinal community
      studies in Tanzania and Zimbabwe were used, both of which have collected
      information on the HIV status of the population over a prolonged period and
      maintained a demographic surveillance system that collects information on cause
      of death through verbal autopsy. The algorithm was then tested in different times
      (two phases of the Zimbabwe study) and different places (Tanzania and Zimbabwe).
      RESULTS: The trained algorithm, including nine signs and symptoms, performed
      consistently based on sensitivity and specificity on verbal autopsy data for
      deaths in 15-44-year-olds from Zimbabwe phase I (sensitivity 79%; specificity
      79%), phase II (sensitivity 83%; specificity 75%) and Tanzania (sensitivity 75%;
      specificity 74%) studies. The sensitivity dropped markedly for classifying deaths
      in 45-59-year-olds. CONCLUSIONS: Verbal autopsy can consistently measure AIDS
      mortality with a set of nine criteria. Surveillance should focus on deaths that
      occur in the 15-44-year age group for which the method performs reliably.
      Addition of a handful of questions related to opportunistic infections would
      enable other widely used verbal autopsy tools to apply this validated method in
      areas for which HIV testing and hospital records are unavailable or incomplete.

PMID- 19854753
TI  - Knowledge-based data analysis comes of age.
AB  - The emergence of high-throughput technologies for measuring biological systems
      has introduced problems for data interpretation that must be addressed for proper
      inference. First, analysis techniques need to be matched to the biological
      system, reflecting in their mathematical structure the underlying behavior being
      studied. When this is not done, mathematical techniques will generate answers,
      but the values and reliability estimates may not accurately reflect the biology.
      Second, analysis approaches must address the vast excess in variables measured
      (e.g. transcript levels of genes) over the number of samples (e.g. tumors, time
      points), known as the 'large-p, small-n' problem. In large-p, small-n paradigms,
      standard statistical techniques generally fail, and computational learning
      algorithms are prone to overfit the data. Here we review the emergence of
      techniques that match mathematical structure to the biology, the use of
      integrated data and prior knowledge to guide statistical analysis, and the recent
      emergence of analysis approaches utilizing simple biological models. We show that
      novel biological insights have been gained using these techniques.

PMID- 19854754
TI  - Changes in blood parameters in New Zealand White rabbits during pregnancy.
AB  - Changes in clinical pathology parameters, particularly those related to blood
      coagulation, were examined throughout the gestation period in New Zealand White
      rabbits. As compared with the non-pregnant group, the following major changes
      were observed in the pregnant group. For blood coagulation-related parameters,
      platelets increased progressively and fibrinogen increased slightly from
      organogenesis, prothrombin time was significantly prolonged during organogenesis
      and shortened in the late fetal growth stage, activated partial thromboplastin
      time was significantly prolonged during the fetal growth stage, and antithrombin
      III increased during and after late organogenesis. Such changes in blood
      coagulation-related parameters during the later stages of gestation seem to be
      physiological responses in preparation for protecting against excessive
      haemorrhage or haemostasis at parturition. For the other haematological and blood
      chemical parameters as well as progesterone, red blood cell counts, haemoglobin
      and haematocrit began to decrease during organogenesis and continued to decrease
      thereafter. Reticulocyte counts significantly increased during organogenesis and
      decreased thereafter. White blood cell parameters, except for neutrophils, showed
      significant decreases during the fetal growth stage. Serum progesterone
      concentration reached its highest level early in organogenesis and decreased
      thereafter. Total protein, albumin, glucose, cholesterol, calcium, blood urea
      nitrogen and creatinine decreased significantly during the middle and/or late
      periods of gestation. In conclusion, the data obtained from the present study can
      be used as background data for effective evaluation of reproductive toxicology in
      rabbits, and pregnant rabbits may serve as models of pregnant women in research
      pertaining to clinical pathology and gestation.

PMID- 19854755
TI  - Rat molar teeth as a study model for direct pulp capping research in dentistry.
AB  - The aim of this review is to evaluate the suitability of rat molar teeth in
      preclinical evaluation of medical devices for direct pulp capping. The ISO
      standard 7405 states clearly that only non-rodent mammals are suitable species
      for animal research in dentistry. Furthermore, without clear justification a
      considerable number of researchers previously rejected results of animal
      experiments concerning preclinical evaluation of the biocompatibility of dental
      materials undertaken in rat molar teeth. However, in the past 50 years about 70
      studies have been published using rat molar teeth in order to evaluate direct
      pulp capping, pulpotomies and tissue reactions after pulp exposure. Numerous
      studies showed that the healing of rat molar pulp tissue after direct pulp
      capping is histologically comparable with humans and other animal species pulp
      tissue. Rat molar teeth, including pulp tissue, can be seen anatomically,
      histologically, biologically, and physiologically as miniature human molar teeth.
      Hence, the essential biological reactions of the pulp tissue and the interaction
      during the different stages of wound healing of rat molar teeth are comparable
      with that of other mammals. Rat molar teeth are a valid study model in order to
      provide valuable data concerning pulp tissue reaction after direct pulp capping
      and related questions in dentistry. Therefore, the use of rats may significantly
      reduce the number of currently used higher animals in research. Tests in higher
      developed animals should be limited to experiments which clarify inconsistent
      results. However, some technical difficulties, like the small size of rat molar
      teeth must be dealt with before undertaking any research.

PMID- 19854756
TI  - Identification methods in newborn C57BL/6 mice: a developmental and behavioural
      evaluation.
AB  - The use of group-housed rodents in many fields of biomedical research imposes a
      need to identify individuals in a cage. Few studies have been designed to assess
      possible negative effects of identification methods of newborn mice on their
      development and wellbeing. In the present study, three different identification
      methods were applied to newborn C57BL/6J mice on postnatal day (pnd) 5 (toe
      clipping, toe tattoo ink puncture and subcutaneous implantation of a small
      transponder). All identification methods used proved to be effective for long
      term marking of individual animals. Newborn mice showed the least reaction to toe
      clipping followed by toe tattoo ink puncture and transponder implantation was the
      most distressful individual identification procedure in newborn mice.
      Importantly, clipped toe tissue proved to be enough for genotyping purposes. No
      overall consistent differences in somatic and neurological reflex development
      during the postnatal period were shown as a result of the newborn individual
      identification procedures used. Further, none of the methods interfered
      significantly with the adult animals' general normal behaviour (e.g. ability to
      move, grasp, climb) and sensory-motor functions as assessed with a simplified
      SHIRPA battery of tests, as well as Rotarod and Elevated Plus Maze tests.
      Postmortem thymus and adrenal gland weights gave no indication of chronic stress
      as a consequence of the identification method. We conclude that toe clipping
      might even be advisable in newborn mice at a very young age, when genotyping is
      needed. Toe tattoo ink puncture is also a good identification method for newborn
      mice and transponder implantation should only be used in older newborns or
      applied at weaning.

PMID- 19854757
TI  - Impact of aspen furniture and restricted feeding on activity, blood pressure,
      heart rate and faecal corticosterone and immunoglobulin A excretion in rats
      (Rattus norvegicus) housed in individually ventilated cages.
AB  - This study aims to evaluate the impact of adding different items in individually
      ventilated rat cages on the animal's activity, cardiovascular parameters and
      faecal stress indicators. The following three cage items made of aspen were
      compared: a cross made of two intersecting boards, a similar cross where drilled
      holes were loaded with food pellets (restricted feeding) and a rectangular tube.
      Male rats of the strains BN and F344 (n = 12) were housed in groups of three; one
      rat in each group was implanted with a telemetric transponder to measure mean
      arterial pressure (MAP) and heart rate (HR). In a crossover design, each group
      spent 14 days with each type of cage furniture, thereafter faecal pellets were
      collected for faecal analyses. The means of activity and means and coefficient of
      variation for MAP and HR were calculated for days 2, 6, 10 and 14. As a way of
      determining which of the statistically significant MAP and HR mean changes were
      biologically meaningful, the night-day differences of the controls on day 14 were
      used. Both board types lowered MAP of F344 rats; hence dividing walls seem
      beneficial for F344 welfare. None of the MAP or HR differences in BN rats were
      biologically significant. No statistically significant differences in faecal
      corticosterone or IgA excretion were detected. In conclusion, provision of
      general recommendations with respect to cage furniture for rat cages is
      complicated because there is a clear genetic component involved in how animals
      respond to these structures.

PMID- 19854758
TI  - Validation of intratracheal instillation of lung tumour cells in mice using
      single photon emission computed tomography/computed tomography imaging.
AB  - In search of better predictive animal models for evaluating treatment response in
      lung cancer, orthotopic lung tumour models are a great step forward over
      traditional subcutaneous models. Crucial in the development of such orthotopic
      models is a reliable and reproducible instillation method. Because cells are
      instilled inside the thorax, the accuracy of the instillation and visualization
      of tumour growth demands the use of non-invasive imaging methods. We used a
      minimally invasive intratracheal intubation method to instill bioluminescent lung
      tumour cells in the lung parenchyma. Adaptation of the cell containing medium
      provides the possibility of tracing the exact location of the injection by means
      of single photon emission computed tomography/computed tomography (CT) imaging.
      The transplantation medium was also optimized to prevent migration of the
      injected substance. This results in the outgrowth of single and well-defined lung
      tumours at the instillation site. Finally, tumour growth was validated and
      longitudinally monitored with a combination of CT and bioluminescence imaging.
      The reported transplantation procedure enables the assessment of injection
      accuracy and provides a good approach for the generation of orthotopic lung
      tumour models for future response imaging studies.

PMID- 19854760
TI  - Does physical activity reduce seniors' need for healthcare?: a study of 24 281
      Canadians.
AB  - OBJECTIVES: Physical inactivity has been associated with significant increases in
      disease morbidity and mortality. This study assessed the association between
      physical activity and (1) health resource use and (2) health resource use costs.
      DESIGN AND PARTICIPANTS: The responses from 24 281 respondents >65 years to the
      Canadian Community Health Survey Cycle 1.1 were used to find activity levels and
      determine health resource use and costs. Logistic regression models were used to
      assess risks of hospitalisation. RESULTS: Physical inactivity was associated with
      statistically significant increases to hospitalisations, lengths of stay and
      healthcare visits (p<0.01). Average healthcare costs (based on the 2007 value of
      the Canadian dollar) for the physically inactive were $C1214.15 higher than the
      healthcare costs of the physically active ($C2005.27 vs $C791.12, p<0.01).
      CONCLUSION: Among those >65 years, physical activity is strongly associated with
      reduced health resource use and costs.

PMID- 19854759
TI  - Some sex hormone profiles are consistent over time in normal menstruating women:
      implications for sports injury epidemiology.
AB  - PURPOSE: It is unclear whether sex hormone profiles obtained in two consecutive
      months are consistent within women. Month-to-month consistency in daily, nadir,
      peak and mean hormone concentrations during the early follicular and luteal
      phases in recreationally active, young eumenorrheic women was prospectively
      examined. METHODS: 60 healthy, non-smoking women who reported normal and
      consistent menstrual cycles lasting 26-32 days for the past 6 months were
      followed prospectively to obtain serum samples for the first 6 days of menses and
      for 8 days after a positive ovulation test over two consecutive months. Month-to
      month consistency of daily concentrations of oestradiol (pg/ml), progesterone
      (ng/ml), testosterone (ng/dl), sex hormone-binding globulin (nmol/l) and free
      androgen index were determined using linear mixed models. Month-to-month
      consistency in nadir, peak and mean concentrations were then assessed using
      intraclass correlation coefficients and SEM to more precisely examine
      intraindividual consistency. RESULTS: Linear mixed models revealed stable hormone
      concentrations across cycles and cycles by day. Reliability estimates for nadir,
      peak, mean menses and mean postovulatory concentrations range from 0.56 to 0.86
      for oestradiol, 0.44 to 0.91 for progesterone, 0.60 to 0.86 for testosterone,
      0.88 to 0.97 for sex hormone-binding globulin and 0.78 to 0.91 for free androgen
      index. CONCLUSIONS: Hormone profiles were reproducible over two consecutive
      months. To reduce month-to-month intraindividual variations and improve
      measurement consistency, it is recommended that multiple samples be taken over
      consecutive days as opposed to a single sample.

PMID- 19854761
TI  - Biological markers of cardiac damage are not related to measures of cardiac
      systolic and diastolic function using cardiovascular magnetic resonance and
      echocardiography after an acute bout of prolonged endurance exercise.
AB  - OBJECTIVES: Seventeen male participants (mean (SD) (range): age 33.5 (6.5) years
      (46-26 years), body mass 80 (9.2) kg (100-63 kg), height 1.81 (0.06) m (1.93-
      1.70 m)) ran a marathon to investigate the relationship between systolic function
      (using cardiac magnetic resonance (CMR)) and diastolic function (using
      echocardiography) against biomarkers of cardiac damage. METHODS:
      Echocardiographic and cardiac troponin I (cTnI)/N-terminal pro-B-type natriuretic
      peptide (NTproBNP) data were collected 24 h premarathon, immediately postmarathon
      and 6 h postmarathon. CMR data were collected 24 h premarathon and at 6 h
      postmarathon. RESULTS: Body mass was significantly reduced postmarathon (80 (9.2)
      vs 78.8 (8.6) kg; p<0.001). There was a significant E/A reduction postmarathon
      (1.11 (0.34) vs 1.72 (0.44); p<0.05) that remained depressed 6 h postmarathon
      (1.49 (0.43); p<0.05). CMR demonstrated left ventricular end-diastolic and end
      systolic volumes were reduced postmarathon, with a preserved stroke volume. Left
      ventricular ejection fraction 6 h postmarathon significantly increased (64.4%
      (4.2%) vs 67.4% (5%); p<0.05). There were significant elevations in cTnI (0.00 vs
      0.04 (0.03) MUg/l; p<0.05) and NTproBNP (37.4 (24.15) ng/l vs 59.34 (43.3) ng/l;
      p<0.05) immediately postmarathon. Eight runners had cTnI elevations immediately
      postmarathon above acute myocardial infarction cutoff levels (>=0.03 MUg/l). No
      correlations between cTnI/NTproBNP and measures of diastolic function (E, A, E/A,
      isovolumic relaxation time, E deceleration time and E/E') or measures of systolic
      function (stroke volume or ejection fraction) were observed immediately
      postmarathon or 6 h postmarathon. CONCLUSIONS: Biomarkers of cardiac damage after
      prolonged exercise are not associated with either systolic or diastolic
      functional measures.

PMID- 19854762
TI  - Induction of TNF-alpha-converting enzyme-ectodomain shedding by pathogenic
      autoantibodies.
AB  - The release of the soluble form of tumor necrosis factor (TNF)-alpha from the
      plasma membrane occurs through the activation of the secretase tumor necrosis
      factor-alpha-converting enzyme (TACE). The current study was designed to examine
      whether the anti-Ro/SSA autoantibodies (Abs) are capable to regulate TACE
      expression in non-neoplastic human salivary gland epithelial cells (SGEC)
      cultures. We investigated the effect of anti-Ro/SSA Abs on the localization and
      abundance of cell-surface TACE and on TACE pro-domain-shedding and activation. In
      addition, the potential physiological consequences of TNF-alpha blockage by the
      biological agent Adalimumab on post-translational regulation of TACE are
      discussed. Anti-Ro/SSA Abs were purified from IgG fractions of patients with
      primary Sjogren's syndrome, using Sepharose 4B-Ro/SSA affinity columns. Flow
      cytometry, reverse transcription-PCR, western blot and immunohistochemistry were
      used to study TACE expression on SGEC and TACE regulation by Abs. Our study
      demonstrated a dose-dependent increase of TACE messenger RNA (mRNA) expression in
      anti-Ro/SSA Abs-treated SGEC, followed by internalization, pro-domain shedding
      and activation of TACE protein, suggesting that increased TACE activity is
      necessary for the release of TNF-alpha observed in anti-Ro/SSA Abs-stimulated
      SGEC. Adalimumab treatment brought TACE mRNA and surface TACE expression to
      levels than those observed in untreated SGEC. These data suggest that the effect
      of anti-Ro/SSA Abs on TACE expression and intracellular distribution is exerted
      by TNF-alpha production.

PMID- 19854763
TI  - SeaView version 4: A multiplatform graphical user interface for sequence
      alignment and phylogenetic tree building.
AB  - We present SeaView version 4, a multiplatform program designed to facilitate
      multiple alignment and phylogenetic tree building from molecular sequence data
      through the use of a graphical user interface. SeaView version 4 combines all the
      functions of the widely used programs SeaView (in its previous versions) and
      Phylo_win, and expands them by adding network access to sequence databases,
      alignment with arbitrary algorithm, maximum-likelihood tree building with PhyML,
      and display, printing, and copy-to-clipboard of rooted or unrooted, binary or
      multifurcating phylogenetic trees. In relation to the wide present offer of tools
      and algorithms for phylogenetic analyses, SeaView is especially useful for
      teaching and for occasional users of such software. SeaView is freely available
      at http://pbil.univ-lyon1.fr/software/seaview.

PMID- 19854764
TI  - Schizophrenia and NICE: all quiet on the community front?

PMID- 19854765
TI  - Are all antidepressants equal?

PMID- 19854766
TI  - Making the best use of available evidence: the case of new generation
      antidepressants: a response to: are all antidepressants equal?

PMID- 19854767
TI  - Cognitive decline fastest in people with Alzheimer's disease compared with other
      dementias.

PMID- 19854768
TI  - Survival after myocardial infarction worse with first episode major depression
      than recurrent major depression.

PMID- 19854769
TI  - Review: clinically important differences between antidepressants.

PMID- 19854770
TI  - In adolescents with SSRI resistant depression, CBT/combined treatment is most
      effective in those with comorbid disorders.

PMID- 19854771
TI  - SSRI plus supportive care more effective than supportive care alone for mild to
      moderate depression.

PMID- 19854772
TI  - Group psychoeducation increases time to recurrence in stabilised bipolar
      disorders.

PMID- 19854773
TI  - Review: lamotrigine may be an effective treatment for clozapine resistant
      schizophrenia.

PMID- 19854774
TI  - Review: limited evidence that adding a second antipsychotic improves clozapine
      treatment in schizophrenia.

PMID- 19854775
TI  - Review: rivastigmine reduces rate of cognitive decline and improves performance
      in mild to moderate Alzheimer's.

PMID- 19854776
TI  - Review: statins do not protect against development of dementia.

PMID- 19854777
TI  - A stepped care intervention is effective for elderly people with subthreshold
      depression or anxiety.

PMID- 19854778
TI  - Review: school based prevention and early intervention programmes reduce anxiety.

PMID- 19854779
TI  - Review: limited evidence to support specialist mental health services as
      alternatives to inpatient care for young people with severe mental health
      disorders.

PMID- 19854780
TI  - Review: limited evidence that psychological therapies are of benefit for adults
      with chronic pain.

PMID- 19854781
TI  - Both focused and enhanced cognitive behavioural therapy improve eating disorder
      symptom severity.

PMID- 19854782
TI  - Peer group support intervention reduces psychological distress in AIDS orphans.

PMID- 19854783
TI  - Incentives increase enrolment in substance abuse treatment at community needle
      exchange site.

PMID- 19854784
TI  - Review: limited evidence to support pharmacological therapy for amphetamine
      withdrawal.

PMID- 19854785
TI  - Young people leaving the UK armed forces at increased risk of suicide.

PMID- 19854786
TI  - Limited evidence that bullying behaviour in children may be linked to later
      suicidal behaviour.

PMID- 19854787
TI  - Antenatal depression predicts depression in adolescent offspring.

PMID- 19854788
TI  - Cancer history may affect link between psychological distress and cancer
      mortality.

PMID- 19854789
TI  - Parental violent crime, previous violence and substance abuse predict future
      violence in people with schizophrenia.

PMID- 19854790
TI  - Review: prevalence of adult ADHD declines with age.

PMID- 19854791
TI  - Does a skeletonized or pedicled left internal thoracic artery give the best graft
      patency?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether skeletonization of the internal
      thoracic artery (ITA) improves graft patency in coronary artery bypass grafting
      (CABG). Altogether >60 papers were found using the reported search, of which 17
      papers represented the best evidence to answer the clinical question. Grafts used
      were either as single ITAs (left or right, LITA or RITA) or bilateral ITAs
      (BITAs). The author, journal, date and country of publication, patient group
      studied, study type, relevant outcomes and results are tabulated. We acknowledge
      that evidence is limited in this area of cardiac surgery. The skeletonized ITA
      has not been used long enough to establish whether a decline in patency will
      occur after several years. The follow-up data was not long-term with only two
      studies providing patency rates beyond five years. Also, only 4 out of 17 papers
      were comparative studies (skeletonized conduits vs. pedicled conduits). However,
      the available evidence demonstrates that short- and medium-term patency rates of
      both skeletonized and pedicled conduits are excellent. In the four comparative
      studies, skeletonization patency was at least comparable to pedicled conduits and
      in two studies even higher. Patency was assessed with the use of angiography,
      performed on average within four years of CABG surgery. Patency rates exceeded
      95% in the 10 non-comparative studies where angiographic follow-up was within
      three years of surgery. This is an important finding because it justifies further
      use of skeletonized technique for CABG surgery. It adds also to a growing field
      of evidence that skeletonized ITA grafts are preferable to pedicled grafts
      because they may cause less degree of devascularization of the sternum and
      consequently reduction of sternal wound infection. The evidence presented here
      demonstrates that in terms of patency, skeletonized and pedicled left internal
      thoracic arteries provide excellent patency rates.

PMID- 19854792
TI  - A single centre experience of simultaneous open abdominal aortic aneurysm and
      cardiac surgery.
AB  - OBJECTIVES: Controversy exists over the optimal management of patients with both
      symptomatic cardiac disease and significant abdominal aortic aneurysm (AAA), but
      who are unsuitable for endovascular treatment for either pathology. We present
      our single centre series of synchronous cardiac and aortic aneurysm surgery in
      patients anatomically unsuitable for endovascular AAA repair. METHODS: All
      patients undergoing synchronous cardiac and open AAA surgery between June 2002
      and December 2008 were analysed using a prospectively maintained database
      supplemented with case note review. RESULTS: Thirteen patients with a median age
      of 78 years underwent combined surgery. Two AAA were juxtarenal and the remainder
      infrarenal with a median diameter of 7 cm (4.8-11), of which three were
      symptomatic. In all cases, endovascular repair was not possible due to either
      hostile iliac or neck anatomy. Eleven patients underwent coronary artery bypass
      grafting (CABG), one CABG plus aortic valve replacement and one patient aortic
      valve replacement only. All patients were operated on cardiopulmonary bypass
      (CPB) and received autologous cell salvaged blood. Median CPB and operative time
      was 182 (141-260) and 420 (360-490) min, respectively. There were two deaths: the
      first after 90 days from multi-organ failure and stroke, the second following
      three days from multi-organ failure. Complications comprised: four transient
      renal impairment; one transient jaundice; four pneumonia; one unstable sternum;
      and four arrhythmias with one patient requiring a permanent pacemaker. Two
      patients suffered transient diarrhoea but no other features of intestinal
      ischaemia. The remaining 11 patients are alive with a median New York Heart
      Association (NYHA) score improvement from III to II at six months. CONCLUSION:
      Simultaneous open repair of AAA and cardiac surgery is a feasible option for this
      high-risk and anatomically challenging patient group. This experience highlights
      the need for close cooperation between vascular and cardiac teams.

PMID- 19854794
TI  - In patients undergoing thoracic surgery is paravertebral block as effective as
      epidural analgesia for pain management?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: in patients undergoing thoracic surgery is
      paravertebral block (PVB) as effective as epidural analgesia for pain management?
      Altogether >184 papers were found using the reported search, seven of which
      represented the best evidence to answer the clinical question. All studies agreed
      that PVB is at least as effective as epidural analgesia for pain control post
      thoracotomy. In one paper, the visual analogue pain score (VAS) at rest and on
      cough was significantly lower in the paravertebral group (P=0.02 and 0.0001,
      respectively). Pulmonary function, as assessed by peak expiratory flow rate
      (PEFR), was significantly better preserved in the paravertebral group. The lowest
      PEFR as a fraction of preoperative control was 0.73 in the paravertebral group in
      contrast with 0.54 in the epidural group (P<0.004). Oximetric recordings were
      better in the paravertebral group (96%) compared to the epidural group (95%)
      (P=0.0001). Another article reported that statistically significant differences
      (forced vital capacity 46.8% for PVB and 39.3% for epidural group P<0.05; forced
      expiratory volume in 1 s (FEV(1)) 48.4% in PVB group and 35.9% in epidural group,
      P<0.05) were reached in day 2 and continued until day 3. Plasma concentrations of
      cortisol, as marker of postoperative stress, increased markedly in both groups,
      but the increment was statistically different in favour of the paravertebral
      group (P=0.003). Epidural block was associated with frequent side-effects
      [urinary retention (42%), nausea (22%), itching (22%) and hypotension (3%) and,
      rarely, respiratory depression (0.07%)]. Additionally, it prolonged operative
      time and was associated with technical failure or displacement (8%). Epidurals
      were also related to a higher complication rate (atelectasis/pneumonia) compared
      to the PVB (2 vs. 0). PVB was found to be of equal efficacy to epidural
      anaesthesia, but with a favourable side effect profile, and lower complication
      rate. The reduced rate of complication was most marked for pulmonary
      complications and is accompanied by quicker return to normal pulmonary function.
      We conclude intercostal analgesia, in the form of PVB, can be at least as
      effective as epidural analgesia.

PMID- 19854793
TI  - Impact of clonidine administration on delirium and related respiratory weaning
      after surgical correction of acute type-A aortic dissection: results of a pilot
      study.
AB  - Delirium and transient neurologic dysfunctions (TND) often complicate the
      postoperative course after surgery for acute type-A aortic dissection (AAD). We
      evaluated the role of clonidine on neurological outcome and respiratory function
      in 30 consecutive patients undergoing surgery for AAD. Patients were
      prospectively randomized to receive either clonidine (0.5 microg/kg bolus,
      followed by continuous infusion at 1-2 microg/kg/h) or placebo (NaCl 0.9%) in on
      starting and throughout the weaning period from the mechanical ventilation.
      Incidence of delirium and TND, Delirium Detection Score (DDS), weaning parameters
      [respiratory rate to tidal volume ratio - f/VT; pressure-frequency product (PFP);
      partial pressure of arterial oxygen to fractional inspired oxygen concentration
      (PaO(2)/FiO(2)); partial pressure of carbon dioxide (PaCO(2))], weaning duration
      and intensive care unit (ICU) length of stay were recorded. The two groups were
      similar for preoperative and operative variables and also for the incidence of
      postoperative complications. DDS was lower in the clonidine group (P<0.001).
      Patients weaned with clonidine showed lower f/VT and PFP, higher PaO(2)/FiO(2)
      and PaCO(2), lower DDS, weaning period and the related ICU length of stay
      (P<0.001). This was further confirmed in patients developing delirium/TND.
      Intravenous clonidine after surgery for AAD reduces the severity of delirium,
      improves the respiratory function, shortens the weaning duration and the ICU
      length of stay.

PMID- 19854795
TI  - Vestibular effects of diving - a 6-year prospective study.
AB  - BACKGROUND: Permanent injuries to the vestibular end organs may occur in diving
      due to decompression illness (DCI) or barotraumas. This may lead to distressing
      long-term symptoms, including dizziness and disequilibrium. AIMS: To look for
      evidence of vestibular disorders in working divers and to relate this to diving
      exposure or injuries. METHODS: A cohort of 67 men aged 28 +/- 5 years (mean +/-
      SD) completing a basic course for working divers answered a questionnaire and
      underwent clinical otoneurological examination, electronystagmography (ENG),
      including alternate bithermal caloric tests and platform posturography. The
      procedure was repeated after 3 and 6 years. RESULTS: At follow-up, none of the
      divers had experienced inner ear barotraumas or inner ear DCI. Two cases of
      untreated probable DCI were diagnosed retrospectively in 27 232 dives. Middle ear
      barotrauma was reported by 36%. There was no correlation between diving frequency
      and postural sway at follow-up. Transient dizziness during or shortly after a
      dive was reported by 63 and 15%, respectively. The prevalence of dizziness on
      land and ENG abnormalities did not change during follow-up. No vestibular
      disorders were diagnosed. CONCLUSIONS: Transient vestibular symptoms and middle
      ear barotraumas are common in diving. This study found no evidence of long-term
      vestibular effects. Vestibular disorders in divers are probably related to
      singular events, like inner ear barotraumas or inner ear DCI, rather than
      frequent diving per se.

PMID- 19854796
TI  - Acute signalling responses to intense endurance training commenced with low or
      normal muscle glycogen.
AB  - We have previously demonstrated that well-trained subjects who completed a 3 week
      training programme in which selected high-intensity interval training (HIT)
      sessions were commenced with low muscle glycogen content increased the maximal
      activities of several oxidative enzymes that promote endurance adaptations to a
      greater extent than subjects who began all training sessions with normal glycogen
      levels. The aim of the present study was to investigate acute skeletal muscle
      signalling responses to a single bout of HIT commenced with low or normal muscle
      glycogen stores in an attempt to elucidate potential mechanism(s) that might
      underlie our previous observations. Six endurance-trained cyclists/triathletes
      performed a 100 min ride at approximately 70% peak O(2) uptake (AT) on day 1 and
      HIT (8 x 5 min work bouts at maximal self-selected effort with 1 min rest) 24 h
      later (HIGH). Another six subjects, matched for fitness and training history,
      performed AT on day 1 then 1-2 h later, HIT (LOW). Muscle biopsies were taken
      before and after HIT. Muscle glycogen concentration was higher in HIGH versus LOW
      before the HIT (390 +/- 28 versus 256 +/- 67 micromol (g dry wt)(1)). After HIT,
      glycogen levels were reduced in both groups (P < 0.05) but HIGH was elevated
      compared with LOW (229 +/- 29 versus 124 +/- 41 micromol (g dry wt)(1); P <
      0.05). Phosphorylation of 5 AMP-activated protein kinase (AMPK) increased after
      HIT, but the magnitude of increase was greater in LOW (P < 0.05). Despite the
      augmented AMPK response in LOW after HIT, selected downstream AMPK substrates
      were similar between groups. Phosphorylation of p38 mitogen-activated protein
      kinase (p38 MAPK) was unchanged for both groups before and after the HIT training
      sessions. We conclude that despite a greater activation AMPK phosphorylation when
      HIT was commenced with low compared with normal muscle glycogen availability, the
      localization and phosphorylation state of selected downstream targets of AMPK
      were similar in response to the two interventions.

PMID- 19854797
TI  - The pulmonary system during exercise in hypoxia and the cold.
AB  - The demands for pulmonary O(2) and CO(2) transport in the exercising human are
      substantial. Fortunately, the regulatory and architectural limits of the
      pulmonary system meet the requirements of heavy exercise in most individuals.
      However, in some highly trained athletes the high metabolic demand of intense
      exercise is in excess of the capacity of the pulmonary system. Environmental
      considerations, in addition to those imposed by the demands of exercise, provide
      further physiological challenges that must be met. Winter athletes often
      encounter high-altitude hypoxia and cold, either transiently during competition
      or repeatedly during training. In this brief review, we examine the pulmonary
      system during acute and chronic exercise in hypoxic and cold environmental
      conditions. Observations from studies conducted in humans are emphasized in order
      to ask questions about regulation, plasticity and the limits of human physiology.
      We also highlight new findings and controversial questions that would benefit
      from additional study.

PMID- 19854798
TI  - New insights on the effects of heat stress on crops.

PMID- 19854799
TI  - Developmental and heat stress-regulated expression of HsfA2 and small heat shock
      proteins in tomato anthers.
AB  - The high sensitivity of male reproductive cells to high temperatures may be due
      to an inadequate heat stress response. The results of a comprehensive expression
      analysis of HsfA2 and Hsp17-CII, two important members of the heat stress system,
      in the developing anthers of a heat-tolerant tomato genotype are reported here. A
      transcriptional analysis at different developmental anther/pollen stages was
      performed using semi-quantitative and real-time PCR. The messengers were
      localized using in situ RNA hybridization, and protein accumulation was monitored
      using immunoblot analysis. Based on the analysis of the gene and protein
      expression profiles, HsfA2 and Hsp17-CII are finely regulated during anther
      development and are further induced under both short and prolonged heat stress
      conditions. These data suggest that HsfA2 may be directly involved in the
      activation of protection mechanisms in the tomato anther during heat stress and,
      thereby, may contribute to tomato fruit set under adverse temperatures.

PMID- 19854800
TI  - Overexpression of the CBF2 transcriptional activator in Arabidopsis delays leaf
      senescence and extends plant longevity.
AB  - Leaf senescence is a programmed developmental process governed by various
      endogenous and exogenous factors, such as the plant developmental stage, leaf
      age, phytohormone levels, darkness, and exposure to stresses. It was found that,
      in addition to its well-documented role in the enhancement of plant frost
      tolerance, overexpression of the C-repeat/dehydration responsive element binding
      factor 2 (CBF2) gene in Arabidopsis delayed the onset of leaf senescence and
      extended the life span of the plants by approximately 2 weeks. This phenomenon
      was exhibited both during developmental leaf senescence and during senescence of
      detached leaves artificially induced by either darkness or phytohormones.
      Transcriptome analysis using the Affymetrix ATH1 genome array revealed that
      overexpression of CBF2 significantly influenced the expression of 286 genes in
      mature leaf tissue. In addition to 30 stress-related genes, overexpression of
      CBF2 also affected the expression of 24 transcription factor (TF) genes, and 20
      genes involved in protein metabolism, degradation, and post-translational
      modification. These results indicate that overexpression of CBF2 not only
      increases frost tolerance, but also affects other developmental processes, most
      likely through interactions with additional TFs and protein modification genes.
      The present findings shed new light on the crucial relationship between plant
      stress tolerance and longevity, as reported for other eukaryotic organisms.

PMID- 19854801
TI  - Flower numbers, pod production, pollen viability, and pistil function are reduced
      and flower and pod abortion increased in chickpea (Cicer arietinum L.) under
      terminal drought.
AB  - Terminal drought during the reproductive stage is a major constraint to yield of
      chickpea in many regions of the world. Termination of watering (WS) during
      podding in a small-seeded desi chickpea (Cicer arietinum L.) cultivar, Rupali,
      and a large-seeded kabuli chickpea cultivar, Almaz, induced a decrease in predawn
      leaf water potential (LWP), in the rate of photosynthesis, and in stomatal
      conductance. Compared to well-watered (WW) controls, the WS treatment reduced
      flower production by about two-thirds. In the WW treatment, about 15% of the
      flowers aborted and 42% (Rupali) and 67% (Almaz) of the pods aborted, whereas in
      the WS treatment 37% and 56% of the flowers aborted and 54% and 73% of the pods
      aborted, resulting in seed yields of 33% and 15% of the yields in WW plants in
      Rupali and Almaz, respectively. In vitro pollen viability and germination in
      Rupali decreased by 50% and 89% in the WS treatment, and pollen germination
      decreased by 80% in vivo when pollen from a WS plant was placed on a stigma of a
      WW plant. While about 37% of the germinated pollen tubes from WW plants and 22%
      from the WS plants reached the ovary in the WW plants, less than 3% of pollen
      grains reached the ovary when pollen from either WS or WW plants was placed on a
      stigma of a WS plant. It is concluded that, in addition to pod abortion, flower
      abortion is an important factor limiting yield in chickpea exposed to terminal
      drought and that water deficit impaired the function of the pistil/style more
      than the pollen.

PMID- 19854802
TI  - Maternal effects for preterm birth: a genetic epidemiologic study of 630,000
      families.
AB  - This study was undertaken to disentangle the maternal genetic from the fetal
      genetic effects for preterm birth and to study the possibility of these effects
      being explained by known risk factors. By cross-linking of the population-based
      Swedish Multigeneration and Medical Birth registers, 989,027 births between 1992
      and 2004 were identified. Alternating logistic regression was applied to model
      the familial clustering with pairwise odds ratios (PORs), and covariates were
      included to evaluate if the familial aggregation was explained by exposure to
      shared risk factors. Generalized linear mixed models were used to estimate the
      contribution of genetic and environmental effects. Sisters of women who had a
      preterm delivery had themselves an increased odds of having a preterm delivery
      (POR = 1.8, 95% confidence interval: 1.5, 2.1), while there was no corresponding
      increase in odds in families joined by brothers (POR = 1.1, 95% confidence
      interval: 0.9, 1.4). Twenty-five percent of the variation in preterm birth was
      explained by maternal genetic factors, whereas fetal genetic factors only
      marginally influenced the variation in liability. The increased odds ratio
      between offspring of sisters was independent of maternal risk factors for preterm
      birth, suggesting that the relative importance of maternal effects is not
      explained by these well-known risk factors.

PMID- 19854803
TI  - Estimation of the contribution of non-assisted reproductive technology ovulation
      stimulation fertility treatments to US singleton and multiple births.
AB  - Infertility treatments that include ovulation stimulation, both assisted
      reproductive technologies (ARTs) and non-ART ovulation stimulation, are
      associated with increased risks of multiple birth and concomitant sequelae and
      adverse outcomes, even among singletons. While a US surveillance system for ART
      induced births is ongoing, no population-based tracking system exists for births
      resulting from non-ART treatments. The authors developed a multistage model to
      estimate the uncertain proportion of US infants born in 2005 who were conceived
      by using non-ART ovulation treatments. Using published surveillance data, they
      estimated proportions of US multiple births conceived naturally and by ART and
      assumed that the remainder were conceived with non-ART treatments. They used
      Bayesian meta-analyses to summarize published clinical studies on the multiple
      gestation risk associated with non-ART ovulation treatments, applied a fetal
      survival factor, and used this multiple-birth risk estimate and their own
      estimate of the proportion of US multiple births attributable to non-ART
      ovulation stimulation to estimate the total (and, through subtraction, singleton)
      proportion of infants conceived with such treatments. On the basis of the model,
      the authors estimate that 4.6% of US infants born in 2005 (95% uncertainty range:
      2.8%-7.1%) resulted from non-ART ovulation treatments. Notably, this figure is 4
      times greater than the ART contribution.

PMID- 19854804
TI  - The genetics of preterm birth: using what we know to design better association
      studies.
AB  - Women delivering preterm are at greatly increased risk of another preterm birth
      in subsequent pregnancies, reflecting effects of the environment, genetics, or
      both. Recent literature tells an increasingly coherent story about genetic
      susceptibility. Women who change partners after delivering preterm retain their
      elevated risk, whereas fathers who change partners do not. Women who themselves
      were preterm are at increased risk, an association not seen in fathers. Women
      with a half-sister who delivered preterm are at increased risk only if the shared
      parent was the mother. Concordance for preterm delivery is elevated in
      monozygotic compared with dizygotic twin mothers but not in monozygotic twin
      fathers. Several mechanisms could be operating: mitochondrial genes, maternal
      genes, or fetal genes expressing only the maternally derived copy. The authors
      compare 3 study designs for their ability to detect variants and to distinguish
      among mechanisms underlying heritability of this common outcome. The case-parent
      triad design offers robustness against self-selection and genetic population
      stratification, providing for estimation of genetic effects that are fetal,
      maternal, or that depend on the parent of origin. A case-base approach compares
      case-mothers with randomly sampled baby-mother pairs and permits estimation of
      the same relative risk parameters. Both designs offer important advantages over
      the commonly applied case-mother/control-mother design.

PMID- 19854805
TI  - Invited commentary: maternal effects in preterm birth--effects of maternal
      genotype, mitochondrial DNA, imprinting, or environment?
AB  - Preterm birth is an important public health problem. A wide range of risk factors
      has been investigated, of which the strongest established is a woman's previous
      history of preterm birth. In this issue of the Journal, Boyd et al. (Am J
      Epidemiol. 2009;170(11):1358-1364) and Svensson et al. (Am J Epidemiol.
      2009;170(11):1365-1372), using data on singleton livebirths from national birth
      registers linked with multigeneration databases, found evidence that maternal
      genetic factors impact on the risk for preterm birth, whereas paternal and
      probably fetal genetic factors do not. Possible caveats include missing
      information, the range of maternal risk factors included in the analyses,
      possible misclassification of these risk factors, and possible vertical
      transmission of microbial flora or behaviors from mother to daughter. Weinberg
      and Shi (Am J Epidemiol. 2009;170(11):1373-1381) build on the evidence regarding
      potential mechanisms underlying the heritability of preterm birth from these 2
      and other studies, to evaluate the comparative ability of different study designs
      to distinguish among these potential mechanisms. These studies have different
      strengths, and a portfolio of studies of different designs and with more detailed
      phenotyping than previously done will be needed to probe further the etiology of
      preterm birth and thereby provide tools for its control.

PMID- 19854806
TI  - Svensson et al. respond to "Maternal genes and environment in preterm birth".

PMID- 19854807
TI  - Maternal contributions to preterm delivery.
AB  - Preterm delivery (PTD) is a complex trait with a significant familial component.
      However, no specific inheritance patterns have been established. The authors
      examined the contribution of PTDs in both the woman's family and her partner's
      family to her risk of PTD. The authors linked birth information from Danish
      national registers with pedigree information from the Danish Family Relations
      Database for 1,107,124 live singleton deliveries occurring from 1978 to 2004.
      Risk ratios were estimated comparing women with and without various PTD
      histories. Women with previous PTDs were at greatly increased risk of recurrent
      PTD (risk ratio = 5.6, 95% confidence interval: 5.5, 5.8); however, their PTD
      risk was unaffected by a partner's history of preterm children with other women.
      PTDs to a woman's mother, full sisters, or maternal half-sisters also increased
      her PTD risk (risk ratio = 1.6, 95% confidence interval: 1.5, 1.6), whereas PTDs
      in her paternal half-sisters, the female partners of her male relatives, or
      members of her partner's family did not affect her PTD risk. Inheritance patterns
      were similar for all gestational ages from very early through late PTD. The
      substantial portion of PTD risk explained by effects passed through the female
      line suggests a role for either imprinting or mitochondrial inheritance.

PMID- 19854810
TI  - Sensitivity and specificity of autoantibody tests in the differential diagnosis
      of lupus nephritis.
AB  - Several studies have investigated the potential of various autoantibody tests in
      the diagnosis of systemic lupus erythematosus (SLE). Many lupus patients
      initially present with glomerulonephritis. In that clinical situation the main
      differential diagnosis are other forms of glomerulonephritis. In this study the
      diagnostic value of nine test kits for autoantibody against ANA, dsDNA,
      circulating immune complexes, C1q, nucleosomes, histones and Sm as well as C3 and
      C4 levels was evaluated in 39 patients with biopsy-proven lupus nephritis in
      comparison to 43 patients suffering from other forms of glomerulonephritis. The
      most useful test was an anti-nucleosome antibody enzyme-linked immunosorbent
      assay (ELISA) with a sensitivity of 90% and a specificity of 88%. All tests for
      anti-dsDNA antibodies (Crithidia luciliae Anti-dsDNA, BINDAZYME Anti-dsDNA,
      FARRZYME high avidity Anti-dsDNA) were of moderate sensitivity and very good
      specificity. Decreasing the cut-off for the conventional anti-dsDNA ELISA
      (BINDAZYME) considerably increased its sensitivity (87%) without loss of
      specificity (90%). Tests for anti-C1q and immune complexes performed worse than
      the antidsDNA tests. As anti-histone and Sm antibodies are present only in a
      minority of lupus nephritis patients they are of limited value in diagnosing the
      disease. In conclusion, testing for anti-nucleosome antibodies and the
      conventional anti-dsDNA ELISA with lower cut-off provide the best diagnostic aids
      for differentiation of lupus nephritis from other forms of glomerulonephritis.

PMID- 19854811
TI  - Work disability in systemic lupus erythematosus is prevalent and associated with
      socio-demographic and disease related factors.
AB  - Our objectives were to examine the prevalence of work disability (WD) and factors
      associated with job loss in systemic lupus erythematosus (SLE) in a large, multi
      centered Canadian sample to determine the current prevalence of WD and identify
      the contribution of disease activity, damage, and co-morbidities with respect to
      WD in this cohort. Cross-sectional data on WD status from the 1000 Canadian Faces
      of Lupus database (a multi-center multi-ethnic cohort of SLE patients) along with
      clinical measures (number of ACR criteria ever, SLICC Damage Index, SLAM, SLEDAI,
      SF-36 and Charlson Co-morbidity Index scores), demographic features (age, sex,
      high school education, household income, marital status, disease duration,
      employment status) and co-morbidities (including self-reported fibromyalgia,
      arthralgias, depression and fatigue) were used in bivariate and logistic
      regression analyses. The 1137 SLE patients had a mean age of 50 years (SE 0.75)
      and mean disease duration was 18 years (SE 0.70); 19.09% were work disabled and
      49.78% were employed. Those with WD were more likely than non-WD SLE patients to
      have: a higher number of ACR criteria for SLE; not completed high school; older
      age; single marital status; a lower household income; longer disease duration;
      higher SLICC Damage Index and SLAM scores; lower SF-36 PCS and SF-36 MCS scores;
      less vigorous activity per week; and fibromyalgia, arthralgias, fatigue and
      depression (p < 0.05). This contemporary rate of WD is lower than many past
      reports. Socio-demographic factors, co-morbidities (fibromyalgia and fatigue) and
      disease related factors were strongly associated with WD. We cannot determine
      cause and effect as the study was cross-sectional.

PMID- 19854812
TI  - Evaluation of the maturity of organic waste composts.
AB  - Olive-mill wastes represent a significant environmental problem in Mediterranean
      areas due to their significant production during a short period of time. Their
      high polyphenol, lipid and organic acid concentrations make them phytotoxic
      wastes. Composting is one of the technologies used for the valorization of those
      wastes, producing a fertilizer useful for poor soils. The present study is an
      attempt to elaborate upon organic matter transformations and define the
      parameters for product maturity by adapting chemical and spectroscopic methods
      during composting. The aim of this work was to study the changes involved in the
      composting process of four piles during 200 days, and follow up the maturity of
      the final product during composting. Fourier transform infrared (FTIR)
      spectroscopy has been proven to be an appropriate analytical method for the
      qualitative assessment of compost stability. FTIR spectroscopy results revealed
      enrichment in aromatic structures and a degradation of the aliphatic and
      alcoholic structures indicating stabilization of the final compost. The results
      showed that stability of the final product was reached after 7 months of
      composting. The phytotoxic effects of olive mill wastes and animal manures was
      assessed by germination index. Indeed, the germination indices of piles 1, 2, 3
      and 4 reached 131.31%, 72%, 90.56%, and 105.37%, respectively, at the end of the
      process. This demonstrated the absence of phytotoxicity in the majority of mature
      composts.

PMID- 19854813
TI  - Broadening GHG accounting with LCA: application to a waste management business
      unit.
AB  - In an effort to obtain the most accurate climate change impact assessment,
      greenhouse gas (GHG) accounting is evolving to include life-cycle thinking. This
      study (1) identifies similarities and key differences between GHG accounting and
      life-cycle assessment (LCA), (2) compares them on a consistent basis through a
      case study on a waste management business unit. First, GHG accounting is
      performed. According to the GHG Protocol, annual emissions are categorized into
      three scopes: direct GHG emissions (scope 1), indirect emissions related to
      electricity, heat and steam production (scope 2) and other indirect emissions
      (scope 3). The LCA is then structured into a comparable framework: each LCA
      process is disaggregated into these three scopes, the annual operating activities
      are assessed, and the environmental impacts are determined using the IMPACT2002+
      method. By comparing these two approaches it is concluded that both LCA and GHG
      accounting provide similar climate change impact results as the same major GHG
      contributors are determined for scope 1 emissions. The emissions from scope 2
      appear negligible whereas emissions from scope 3 cannot be neglected since they
      contribute to around 10% of the climate change impact of the waste management
      business unit. This statement is strengthened by the fact that scope 3 generates
      75% of the resource use damage and 30% of the ecosystem quality damage
      categories. The study also shows that LCA can help in setting up the framework
      for a annual GHG accounting by determining the major climate change contributors.

PMID- 19854814
TI  - Private sector involvement in solid waste management in the Greater Accra
      Metropolitan Area in Ghana.
AB  - Solid waste management (SWM) is becoming a major issue in most cities where the
      provision of such public service had hitherto been the sole responsibility of
      central government. However, the costs involved and the rate of waste generation
      have virtually forced city authorities to seek new arrangements with the private
      sector. This paper reviews public-private partnership (PPP) in SWM in the Greater
      Accra Metropolitan Area (GAMA) and reveals that the policy worked well until one
      of the stakeholders failed to deliver. It maintains that harnessing the social
      support, acceptability and participation is key to sustainable PPP. The paper
      calls for institutional and private sector collaboration.

PMID- 19854815
TI  - Study on the inhibition of methane production from anaerobic digestion of
      biodegradable solid waste.
AB  - The inhibition effects and mechanisms of chlorinated methane, anthraquinone and
      acetylene on methanogenesis in the anaerobic digestion process of biodegradable
      solid wastes were investigated. It was found that both chloroform and acetylene
      could effectively inhibit methanogens. Acetylene inhibited the activity of
      methanogens, while chloroform inhibited metabolic process of methanogenesis. A
      central composite design (CCD) and response surface regression analysis (RSREG)
      were employed to determine the optimum conditions and interaction effects of
      chloroform and acetylene in terms of methane and hydrogen production. Acetylene
      promoted the inhibition efficiency (F = 31.14; P < 0.01) more effectively than
      chloroform (F = 2.46; P > 0.05). In addition, a maximum hydrogen production of
      1.6 ml was estimated under the optimum conditions of chloroform concentration of
      6.69 mg kg(-1) and acetylene concentration of 3.08 x 10(-3) (v/v). Chloroform had
      a significant effect on enhancing the production of propionic acid and a minimum
      molar ratio of acetic acid to propionic acid of 0.707 was reached with the
      chloroform concentration of 9.24 mg kg(-1) and acetylene concentration of 4.0 x
      10(-3) (v/v). Hence, methanogens can be inhibited while the stabilization process
      of solid wastes can still work well. Moreover, co-inhibition technology practice
      at landfills was feasible and the environmental damage was negligible, according
      to the analysis and experimental results.

PMID- 19854816
TI  - Planning of municipal solid waste management under dual uncertainties.
AB  - Municipal solid waste management is a complex and multidisciplinary problem,
      involving a number of impact factors associated with various uncertainties. In
      this study, a hybrid interval-parameter possibilistic programming (IPP) approach
      was developed and applied for planning municipal solid waste management under
      dual uncertainties. The IPP improves upon the existing management approaches by
      allowing possibility distributions of the lower and upper bounds of some interval
      parameters in the objective function and interval information in the modelling
      coefficients to be effectively incorporated within its optimization. By
      introducing the concept of possibilistic interval numbers, the dual uncertainties
      can be communicated into the optimization process and the resulting solutions,
      such that the generated decision schemes can effectively reflect the highly
      complex system features under uncertainty. The results of the case study indicate
      that useful information can be obtained for providing feasible decision schemes
      for waste flow allocation. Different decision schemes can be generated by
      adjusting waste flow allocation patterns within the solution intervals. Lower
      decision variable values should be used to obtain lower system cost of waste
      treatment and disposal under advantageous conditions, and higher decision
      variable values should be used under demanding conditions (worst case
      conditions). A strong desire to acquire the lower system cost will lead to the
      decreased probability of meeting the treatment and disposal requirements (i.e.
      the increased risk of unforeseen conditions); willingness to accept the upper
      limit of the system cost will guarantee that waste treatment and disposal
      requirements are met.

PMID- 19854817
TI  - Recycling of paper: accounting of greenhouse gases and global warming
      contributions.
AB  - Greenhouse gas (GHG) emissions have been established for recycling of paper waste
      with focus on a material recovery facility (MRF). The MRF upgrades the paper and
      cardboard waste before it is delivered to other industries where new paper or
      board products are produced. The accounting showed that the GHG contributions
      from the upstream activities and operational activities, with global warming
      factors (GWFs) of respectively 1 to 29 and 3 to 9 kg CO(2)-eq. tonne(- 1) paper
      waste, were small in comparison wih the downstream activities. The GHG
      contributions from the downstream reprocessing of the paper waste ranged from
      approximately 490 to 1460 kg CO(2)-eq. tonne( -1) of paper waste. The system may
      be expanded to include crediting of avoided virgin paper production which would
      result in GHG contributions from -1270 to 390 kg CO(2)-eq. tonne(- 1) paper
      waste. It may also be assumed that the wood not used for virgin paper production
      instead is used for production of energy that in turn is assumed to substitute
      for fossil fuel energy. This would result in GHG contributions from -1850 to 
      4400 kg CO(2)-eq. tonne(- 1) of paper waste. These system expansions reveal very
      large GHG savings, suggesting that the indirect upstream and operational GHG
      contributions are negligible in comparison with the indirect downstream
      emissions. However, the data for reprocessing of paper waste and the data for
      virgin paper production are highly variable. These differences are mainly related
      to different energy sources for the mills, both in regards to energy form (heat
      or electricity) and fuel (biomass or fossil fuels).

PMID- 19854818
TI  - Mold and mycotoxin symposium: towards healthy homes.

PMID- 19854819
TI  - Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure.
AB  - Human exposure to molds, mycotoxins, and water-damaged buildings can cause
      neurologic and neuropsychiatric signs and symptoms. Many of these clinical
      features can partly mimic or be similar to classic neurologic disorders including
      pain syndromes, movement disorders, delirium, dementia, and disorders of balance
      and coordination. In this article, the author delineates the signs and symptoms
      of a syndrome precipitated by mold and mycotoxin exposure and contrasts and
      separates these findings neurodiagnostically from known neurologic diseases. This
      clinical process is designed to further the scientific exploration of the
      underlying neuropathophysiologic processes and to promote better understanding of
      effects of mold/mycotoxin/water-damaged buildings on the human nervous system and
      diseases of the nervous system. It is clear that mycotoxins can affect sensitive
      individuals, and possibly accelerate underlying neurologic/pathologic processes,
      but it is crucial to separate known neurologic and neuropsychiatric disorders
      from mycotoxin effects in order to study it properly.

PMID- 19854820
TI  - Molds, mycotoxins, and sick building syndrome.
AB  - The following is a review of some of the work we have done since 2004 regarding
      the importance of molds and their mycotoxins in the phenomenon of sick building
      syndrome (SBS). In these studies we showed that the macrocyclic trichothecene
      mycotoxins (MTM) of Stachybotrys chartarum (SC) are easily dissociated from the
      surface of the organism as it grows and could therefore be consequently spread in
      buildings as the fungus experiences additional water events. We then showed that
      SC and Penicillium chrysogenum (PC) colonies remain viable long after a water
      source has been removed, and the MTM produced by SC remain toxic over extended
      periods of time. We next showed that PC when inhaled, can release in vivo, a
      protease allergen that can cause a significant allergic inflammatory reaction in
      the lungs of mice. We then showed, in a laboratory study, that the MTM of SC can
      become airborne attached to spores or SC particulates smaller than spores.
      Following that study, we next showed that the same phenomenon actually occurred
      in SC infested buildings where people were complaining of health problems
      potentially associated with SBS. Finally, we were able to demonstrate the
      presence of MTM in the sera of individuals who had been exposed to SC in indoor
      environments. This last study was done with enough mold exposed individuals to
      allow for the statistical significance of SC exposure to be evaluated.

PMID- 19854821
TI  - The treatment of patients with mycotoxin-induced disease.
AB  - Twenty-eight incapacitated individuals (average 43 years old, 7 males, 21
      females, range 12-70) exposed to molds and mycotoxins were studied and treated
      with a protocol of cleaning up or changing their environment to be mold free.
      Injections of the optimum dose of antigens were given as part of the treatment
      protocol as was oral and intravenous (i.v.) antioxidants; heat depuration
      (sauna); physical therapy with massage and exercise under environmentally
      controlled conditions; oxygen therapy at 4-8 L/min for 2 hours with a special
      wood-grade cellophane reservoir and a glass oxygen container. Many patients were
      sensitive to plastics; therefore, exposures to these were kept to a minimum.
      Autogenous lymphocytic factor was given as an immune modulator. Of 28 patients,
      27 did well and returned to work. One patient improved but did not return to work
      during the period of study.

PMID- 19854822
TI  - Molds, mycotoxins, and nutrition.
AB  - Many of the patients with mold and chemical exposure that come to Environmental
      Health Center - Dallas (EHC-D) show signs of impaired digestion. Improving their
      digestion improves their nutritional status and also improves their
      detoxification abilities. Mold and chemical exposure also affect the patient's
      short-term memory and executive function. This presents a challenge when it comes
      to teaching the patient how to improve their nutritional status and
      detoxification. At the EHC-D, we use several instructions methods that have
      resulted in the patient's grasping the concepts and then being able to implement
      the required changes.

PMID- 19854823
TI  - Mold remediation in a hospital.
AB  - As occupants in a hospital, patients are susceptible to air contaminants that can
      include biological agents dispersed throughout the premise. An exposed patient
      can become ill and require medical intervention. A consideration for patients is
      that they may have become environmentally sensitive and require placement in an
      environment that does not compromise their health. Unfortunately, the hospital
      environment often contains more biological substances than can be expected in an
      office or home environment. When a hospital also experiences water intrusion such
      as flooding or water leaks, resulting mold growth can seriously compromise the
      health of patients and others such as nursing staff and physicians (Burge, Indoor
      Air and Infectious Disease. Occupational Medicine: State of the Art Reviews,
      1980; Lutz et al., Clinical Infectious Diseases 37: 786-793, 2003). Micro
      organism growth can propagate if the water is not addressed quickly and
      effectively. Immunocompromised patients are particularly at risk when subjected
      to fungal infection such that the US Center for Disease Control issued guideline
      for building mold in health care facilities (Centers for Disease and Control
      [CDC], Centers for Disease and Control: Questions and Answers on Stachybotrys
      chartarum and Other Molds, 2000). This paper is based on mold remediation of one
      portion of a hospital unit due to water from construction activity and inadequate
      maintenance, resulting in mold growth. A large proportion of the hospital staff,
      primarily nurses in the dialysis unit, exhibited health symptoms consistent with
      mold exposure. Unfortunately, the hospital administrators did not consider the
      mold risk to be serious and refused an independent consultant retained by the
      nurse's union to examine the premise (Canadian Broadcasting Corporation [CBC],
      Nurses file complaints over mold at Foothills. Canadian Broadcasting Corporation,
      2003). The nurse's union managed to have the premise examined by submitting a
      court order of detention and inspection and for an interlocutory injunction to
      allow their consultants to undertake air quality testing. Mold remediation
      procedures are readily available and are not to be discussed here (Silicato,
      http://www.nibs.org/BETEC/M6/ 13-Silicato_Mold-Remediation.pdf, 2004). However,
      the difficulty of determining the qualifications of consultants, contactors and
      project managers are discussed. It also describes the need and importance of a
      buffer zone between the occupied areas and the mold abatement containment area.

PMID- 19854824
TI  - Towards healthy homes.

PMID- 19854825
TI  - UK food agency reaffirms its advice that addition of folic acid to flour should
      be compulsory.

PMID- 19854828
TI  - Tumor necrosis factor alpha represses bone morphogenetic protein (BMP) signaling
      by interfering with the DNA binding of Smads through the activation of NF-kappaB.
AB  - Bone morphogenetic proteins (BMPs) induce not only bone formation in vivo but
      also osteoblast differentiation of mesenchymal cells in vitro. Tumor necrosis
      factor alpha (TNFalpha) inhibits both osteoblast differentiation and bone
      formation induced by BMPs. However, the molecular mechanisms of these inhibitions
      remain unknown. In this study, we found that TNFalpha inhibited the alkaline
      phosphatase activity and markedly reduced BMP2- and Smad-induced reporter
      activity in MC3T3-E1 cells. TNFalpha had no effect on the phosphorylation of
      Smad1, Smad5, and Smad8 or on the nuclear translocation of the Smad1-Smad4
      complex. In p65-deficient mouse embryonic fibroblasts, overexpression of p65, a
      subunit of NF-kappaB, inhibited BMP2- and Smad-induced reporter activity in a
      dose-dependent manner. Furthermore, this p65-mediated inhibition of BMP2- and
      Smad-responsive promoter activity was restored after inhibition of NF-kappaB by
      the overexpression of the dominant negative IkappaBalpha. Although TNFalpha
      failed to affect receptor-dependent formation of the Smad1-Smad4 complex, p65
      associated with the complex. Chromatin immunoprecipitation and electrophoresis
      mobility shift assays revealed that TNFalpha suppressed the DNA binding of Smad
      proteins to the target gene. Importantly, the specific NF-kappaB inhibitor, BAY11
      7082, abolished these phenomena. These results suggest that TNFalpha inhibits BMP
      signaling by interfering with the DNA binding of Smads through the activation of
      NF-kappaB.

PMID- 19854829
TI  - X chromosome-linked inhibitor of apoptosis regulates cell death induction by
      proapoptotic receptor agonists.
AB  - Proapoptotic receptor agonists cause cellular demise through the activation of
      the extrinsic and intrinsic apoptotic pathways. Inhibitor of apoptosis (IAP)
      proteins block apoptosis induced by diverse stimuli. Here, we demonstrate that
      IAP antagonists in combination with Fas ligand (FasL) or the death receptor 5
      (DR5) agonist antibody synergistically stimulate death in cancer cells and
      inhibit tumor growth. Single-agent activity of IAP antagonists relies on tumor
      necrosis factor-alpha signaling. By contrast, blockade of tumor necrosis factor
      alpha does not affect the synergistic activity of IAP antagonists with FasL or
      DR5 agonist antibody. In most cancer cells, proapoptotic receptor agonist-induced
      cell death depends on amplifying the apoptotic signal via caspase-8-mediated
      activation of Bid and subsequent activation of the caspase-9-dependent
      mitochondrial apoptotic pathway. In the investigated cancer cell lines, induction
      of apoptosis by FasL or DR5 agonist antibody can be inhibited by knockdown of
      Bid. However, knockdown of X chromosome-linked IAP (XIAP) or antagonism of XIAP
      allows FasL or DR5 agonist antibody to induce activation of effector caspases
      efficiently without the need for mitochondrial amplification of the apoptotic
      signal and thus rescues the effect of Bid knockdown in these cells.

PMID- 19854830
TI  - Early transcriptional arrest at Escherichia coli rplN and ompX promoters.
AB  - Bacterial transcription elongation factors GreA and GreB stimulate the intrinsic
      RNase activity of RNA polymerase (RNAP), thus helping the enzyme to read through
      pausing and arresting sites on DNA. Gre factors also accelerate RNAP transition
      from initiation to elongation. Here, we characterized the molecular mechanism by
      which Gre factors facilitate transcription at two Escherichia coli promoters,
      PrplN and PompX, that require GreA for optimal in vivo activity. Using in vitro
      transcription assays, KMnO(4) footprinting, and Fe(2+)-induced hydroxyl radical
      mapping, we show that during transcription initiation at PrplN and PompX in the
      absence of Gre factors, RNAP falls into a condition of promoter-proximal
      transcriptional arrest that prevents production of full-length transcripts both
      in vitro and in vivo. Arrest occurs when RNAP synthesizes 9-14-nucleotide-long
      transcripts and backtracks by 5-7 (PrplN) or 2-4 (PompX) nucleotides. Initiation
      factor sigma(70) contributes to the formation of arrested complexes at both
      promoters. The signal for promoter-proximal arrest at PrplN is bipartite and
      requires two elements: the extended -10 promoter element and the initial
      transcribed region from positions +2 to +6. GreA and GreB prevent arrest at PrplN
      and PompX by inducing cleavage of the 3'-proximal backtracked portion of RNA at
      the onset of arrested complex formation and stimulate productive transcription by
      allowing RNAP to elongate the 5'-proximal transcript cleavage products in the
      presence of substrates. We propose that promoter-proximal arrest is a common
      feature of many bacterial promoters and may represent an important physiological
      target of regulation by transcript cleavage factors.

PMID- 19854831
TI  - Translocation of sphingosine kinase 1 to the plasma membrane is mediated by
      calcium- and integrin-binding protein 1.
AB  - SK1 (sphingosine kinase 1) plays an important role in many aspects of cellular
      regulation. Most notably, elevated cellular SK1 activity leads to increased cell
      proliferation, protection from apoptosis, and induction of neoplastic
      transformation. We have previously shown that translocation of SK1 from the
      cytoplasm to the plasma membrane is integral for oncogenesis mediated by this
      enzyme. The molecular mechanism mediating this translocation of SK1 has remained
      undefined. Here, we demonstrate a direct role for CIB1 (calcium and integrin
      binding protein 1) in this process. We show that CIB1 interacts with SK1 in a
      Ca(2+)-dependent manner at the previously identified "calmodulin-binding site" of
      SK1. We also demonstrate that CIB1 functions as a Ca(2+)-myristoyl switch,
      providing a mechanism whereby it translocates SK1 to the plasma membrane. Both
      small interfering RNA knockdown of CIB1 and the use of a dominant-negative CIB1
      we have generated prevent the agonist-dependent translocation of SK1.
      Furthermore, we demonstrate the requirement of CIB1-mediated translocation of SK1
      in controlling cellular sphingosine 1-phosphate generation and associated anti
      apoptotic signaling.

PMID- 19854832
TI  - From molecular biology to geology: a surprising trajectory.

PMID- 19854834
TI  - Transcriptional regulation of membrane lipid homeostasis in Escherichia coli.
AB  - The biophysical properties of membrane phospholipids are controlled by the
      composition of their constituent fatty acids and are tightly regulated in
      Escherichia coli. The FabR (fatty acid biosynthesis repressor) transcriptional
      repressor controls the proportion of unsaturated fatty acids in the membrane by
      regulating the expression of the fabB (beta-ketoacyl-ACP synthase I) and fabA
      (beta-hydroxydecanoyl-ACP dehydratase/isomerase) genes. FabR binding to a DNA
      palindrome located within the promoters of the fabB and fabA genes required the
      presence of an unsaturated acyl-acyl carrier protein (ACP) or acyl-CoA and was
      antagonized by saturated acyl-ACP or acyl-CoA. The FabR-dependent repression of
      fabB and fabA by exogenous unsaturated fatty acids confirmed the role for FabR in
      responding to the acyl-CoA pool composition, and the perturbation of the
      unsaturated:saturated acyl-ACP ratio using a specific inhibitor of lipid A
      formation verified FabR-dependent regulation of fabB by the acyl-ACP composition
      in vivo. Thus, FabR plays a key role in controlling the membrane biophysical
      properties by regulating gene expression in response to the composition of the
      long-chain acyl-thioester pool. This mechanism ensures that a balanced
      composition of fatty acids is available for incorporation into the membrane via
      the PlsB/PlsC acyltransferases.

PMID- 19854833
TI  - Mechanism of lysine oxidation in human lens crystallins during aging and in
      diabetes.
AB  - Oxidative mechanisms during nuclear sclerosis of the lens are poorly understood,
      in particular metal-catalyzed oxidation. The lysyl oxidation product adipic
      semialdehyde (allysine, ALL) and its oxidized end-product 2-aminoadipic acid (2
      AAA) were determined as a function of age and presence of diabetes. Surprisingly,
      whereas both ALL and 2-AAA increased with age and strongly correlated with
      cataract grade and protein absorbance at 350 nm, only ALL formation but not 2-AAA
      was increased by diabetes. To clarify the mechanism of oxidation, rabbit lenses
      were treated with hyperbaric oxygen (HBO) for 48 h, and proteins were analyzed by
      gas and liquid chromatography mass spectrometry for ALL, 2-AAA, and multiple
      glycation products. Upon exposure to HBO, rabbit lenses were swollen, and nuclei
      were yellow. Protein-bound ALL increased 8-fold in the nuclear protein fractions
      versus controls. A dramatic increase in methyl-glyoxal hydroimidazolone and
      carboxyethyl-lysine but no increase of 2-AAA occurred, suggesting more drastic
      conditions are needed to oxidize ALL into 2-AAA. Indeed the latter formed only
      upon depletion of glutathione and was catalyzed by H(2)O(2). Neither
      carboxymethyl-lysine nor glyoxal hydroimidazolone, two markers of glyco
      /lipoxidation, nor markers of lenticular glycemia (fructose-lysine, glucospane)
      were elevated by HBO, excluding significant lipid peroxidation and glucose
      involvement. The findings strongly implicate dicarbonyl/metal catalyzed oxidation
      of lysine to allysine, whereby low GSH combined with ascorbate-derived H(2)O(2)
      likely contributes toward 2-AAA formation, since virtually no 2-AAA formed in the
      presence of methylglyoxal instead of ascorbate. An important translational
      conclusion is that chelating agents might help delay nuclear sclerosis.

PMID- 19854835
TI  - Functional expression of the Na-K-2Cl cotransporter NKCC2 in mammalian cells
      fails to confirm the dominant-negative effect of the AF splice variant.
AB  - The renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is the major salt
      transport pathway in the apical membrane of the mammalian thick ascending limb.
      It is differentially spliced and the three major variants (A, B, and F) differ in
      their localization and transport characteristics. Most knowledge about its
      regulation comes from experiments in Xenopus oocytes as NKCC2 proved difficult to
      functionally express in a mammalian system. Here we report the cloning and
      functional expression of untagged and unmodified versions of the major splice
      variants from ferret kidney (fNKCC2A, -B, and -F) in human embryonic kidney (HEK)
      293 cells. Many NKCC2 antibodies used in this study detected high molecular
      weight forms of the transfected proteins, probably NKCC2 dimers, but not the
      monomers. Interestingly, monomers were strongly detected by phosphospecific
      antibodies directed against phosphopeptides in the regulatory N terminus.
      Bumetanide-sensitive (86)Rb uptake was significantly higher in transfected HEK
      293 cells and could be stimulated by incubating cells in a medium containing a
      low chloride concentration prior the uptake measurements. fNKCC2 was less
      sensitive to the reduction in chloride concentration than NKCC1. Using HEK-293
      cells stably expressing fNKCC2A we also show that co-expression of variant
      NKCC2AF does not have the dominant-negative effect on NKCC2A activity that was
      seen in Xenopus oocytes, nor is it trafficked to the cell surface. In addition,
      fNKCC2AF is neither complex glycosylated nor phosphorylated in its N terminus
      regulatory region like other variants.

PMID- 19854836
TI  - Polycystin-1 interacts with inositol 1,4,5-trisphosphate receptor to modulate
      intracellular Ca2+ signaling with implications for polycystic kidney disease.
AB  - The PKD1 or PKD2 genes encode polycystins (PC) 1 and 2, which are associated with
      polycystic kidney disease. Previously we demonstrated that PC2 interacts with the
      inositol 1,4,5-trisphosphate receptor (IP(3)R) to modulate Ca(2+) signaling.
      Here, we investigate whether PC1 also regulates IP(3)R. We generated a fragment
      encoding the last six transmembrane (TM) domains of PC1 and the C-terminal tail
      (QIF38), a section with the highest homology to PC2. Using a Xenopus oocyte
      Ca(2+) imaging system, we observed that expression of QIF38 significantly reduced
      the initial amplitude of IP(3)-induced Ca(2+) transients, whereas a mutation
      lacking the C-terminal tail did not. Thus, the C terminus is essential to QIF38
      function. Co-immunoprecipitation assays demonstrated that through its C terminus,
      QIF38 associates with the IP(3)-binding domain of IP(3)R. A shorter PC1 fragment
      spanning only the last TM and the C-terminal tail also reduced IP(3)-induced
      Ca(2+) release, whereas another C-terminal fragment lacking any TM domain did
      not. Thus, only endoplasmic reticulum-localized PC1 can modulate IP(3)R. Finally,
      we show that in the polarized Madin-Darby canine kidney cells, heterologous
      expression of full-length PC1 resulted in a smaller IP(3)-induced Ca(2+)
      response. Overexpression of the IP(3)-binding domain of IP(3)R reversed the
      inhibitory effect of PC1, suggesting interaction of full-length PC1 (or its
      cleavage forms) with endogenous IP(3)R in Madin-Darby canine kidney cells. These
      results indicate that the behavior of full-length PC1 in mammalian cells is
      congruent with that of PC1 C-terminal fragments in the oocyte system. These data
      demonstrate that PC1 inhibits Ca(2+) release, perhaps opposing the effect of PC2,
      which facilitates Ca(2+) release through the IP(3)R.

PMID- 19854837
TI  - Loss of the Gata1 gene IE exon leads to variant transcript expression and the
      production of a GATA1 protein lacking the N-terminal domain.
AB  - GATA1 is essential for the differentiation of erythroid cells and megakaryocytes.
      The Gata1 gene is composed of multiple untranslated first exons and five common
      coding exons. The erythroid first exon (IE exon) is important for Gata1 gene
      expression in hematopoietic lineages. Because previous IE exon knockdown analyses
      resulted in embryonic lethality, less is understood about the contribution of the
      IE exon to adult hematopoiesis. Here, we achieved specific deletion of the floxed
      IE exon in adulthood using an inducible Cre expression system. In this
      conditional knock-out mouse line, the Gata1 mRNA level was significantly down
      regulated in the megakaryocyte lineage, resulting in thrombocytopenia with a
      marked proliferation of megakaryocytes. By contrast, in the erythroid lineage,
      Gata1 mRNA was expressed abundantly utilizing alternative first exons.
      Especially, the IEb/c and newly identified IEd exons were transcribed at a level
      comparable with that of the IE exon in control mice. Surprisingly, in the IE-null
      mouse, these transcripts failed to produce full-length GATA1 protein, but instead
      yielded GATA1 lacking the N-terminal domain inefficiently. With low level
      expression of the short form of GATA1, IE-null mice showed severe anemia with
      skewed erythroid maturation. Notably, the hematological phenotypes of adult IE
      null mice substantially differ from those observed in mice harboring conditional
      ablation of the entire Gata1 gene. The present study demonstrates that the IE
      exon is instrumental to adult erythropoiesis by regulating the proper level of
      transcription and selecting the correct transcription start site of the Gata1
      gene.

PMID- 19854838
TI  - Use of erythropoietins in patients with renal transplants.

PMID- 19854839
TI  - Mortality in renal transplant recipients given erythropoietins to increase
      haemoglobin concentration: cohort study.
AB  - OBJECTIVE: To determine the optimal range of increase in haemoglobin
      concentration with treatment with erythropoietins that is safe and is not
      associated with mortality. DESIGN: Retrospective cohort study. The analysis was
      adjusted for several covariables with Cox regression analysis with spline
      functions. Use of erythropoietins, haemoglobin concentration, and covariables
      were included in a time varying manner; variable selection was based on the
      purposeful selection algorithm. SETTING: Transplantation centres in Austria.
      PARTICIPANTS: 1794 renal transplant recipients recorded in the Austrian Dialysis
      and Transplant Registry who received a transplant between 1 January 1992 and 31
      December 2004 and survived at least three months. MAIN OUTCOME MEASURES: Survival
      time and haemoglobin concentration after treatment with erythropoietins. RESULTS:
      The prevalence of use of erythropoietins has increased over the past 15 years to
      25%. Unadjusted extended Kaplan-Meier analysis suggests higher mortality in
      patients treated with erythropoietins, in whom 10 year survival was 57% compared
      with 78% in those not treated with erythropoietins (P<0.001). In the treated
      patients there were 5.4 events/100 person years, compared with 2.6 events/100
      person years in those not treated (P<0.001). After adjustment for confounding by
      indication, comorbidities, comedication, and laboratory readings, haemoglobin
      concentrations >125 g/l were associated with increased mortality in treated
      patients (hazard ratio 2.8 (95% confidence interval 1.0 to 7.9) for haemoglobin
      concentration 140 g/l v 125 g/l), but not in those not treated (0.7, 0.4 to 1.5).
      When haemoglobin concentrations were 147 g/l or above, patients treated with
      erythropoietins showed significantly higher mortality than those who were not
      treated (3.0, 1.0 to 9.4). CONCLUSION: Increasing haemoglobin concentrations to
      above 125 g/l with erythropoietins in renal transplant recipients is associated
      with an increase in mortality. This increase was significant at concentrations
      above 140 g/l.

PMID- 19854840
TI  - Hyperkalaemia.

PMID- 19854841
TI  - Communication during breast cancer treatment.

PMID- 19854842
TI  - Latency of lysosomal proteinases.

PMID- 19854843
TI  - A call for an international collaboration on participatory research for health.
AB  - Participatory health research (PHR) has emerged as an important approach for
      addressing local health issues, including building capacity for health promotion.
      Increasingly, PHR is drawing the attention of communities, funders, decision
      makers and researchers worldwide. It is time to consolidate what we know about
      PHR in order to secure its place as a source of knowledge and action for public
      health. This can be achieved through an International Collaboration on
      Participatory Research for Health to addresses the following issues:Set a
      framework in which information can be exchanged, decisions can be reached and
      information can be disseminated on central issues in PHR. Provide an
      international forum to discuss standards and quality. Produce guidelines for
      researchers, practitioners and community members. Synthesize the findings of PHR
      internationally. Formulate recommendations regarding generalizable findings.
      Similar to the Cochrane Collaboration on clinical trials research, the PHR
      Collaboration will be dependent on a host of experts from various countries to
      bring together what we know about PHR and to make that knowledge accessible to an
      international audience. Unlike the Cochrane Collaboration, the PHR Collaboration
      will include both quantitative and qualitative research approaches. The goal of
      the PHR Collaboration will not be able to achieve a standardization of research
      protocols, but rather to find meaningful ways to judge the quality of PHR and to
      report on its findings while respecting the variety of locally based approaches
      to research design, data collection and interpretation.

PMID- 19854844
TI  - Cardiovascular disease risk factors and women prisoners in the UK: the impact of
      imprisonment.
AB  - Cardiovascular disease (CVD) is a leading cause of death throughout the world. In
      high income countries, the greatest burden of disease is seen in those from lower
      socio-economic groups. It is therefore likely that CVD is an important issue for
      prisoners in the UK, the majority of whom were either unemployed or in non
      skilled employment prior to imprisonment. However, there is little research
      examining this issue. The aim of this study was to examine the prevalence of five
      modifiable cardiovascular risk factors (smoking, physical activity, diet, body
      mass index and hypertension) in women prisoners on entry to prison and then 1
      month after imprisonment. This was a prospective longitudinal study involving 505
      women prisoners in England. Participants completed a questionnaire containing
      questions about health-related behaviours within 72 h of entering prison. The
      researchers measured their blood pressure, height and weight. They followed up
      all participants who were still imprisoned 1 month later and invited them to
      participate again. The results showed that women prisoners were at high risk of
      CVD in the future; 85% smoked cigarettes, 87% were insufficiently active to
      benefit their health, 86% did not eat at least five portions of fruit and
      vegetables each day and 30% were overweight or obese. After 1 month, there were
      few improvements in risk factors. This may in part reflect the fact that, unlike
      prisons in other high income countries, there are currently no systematic
      approaches which address these health issues within UK women's prisons.

PMID- 19854845
TI  - Serum hepcidin-25 levels in patients with chronic kidney disease are independent
      of glomerular filtration rate.
AB  - BACKGROUND: Hepcidin is a key regulator of iron homeostasis and levels are
      elevated in patients with chronic kidney disease (CKD). Hepcidin may explain the
      often observed imbalance in iron metabolism in patients with CKD. We evaluated
      the influence of estimated glomerular filtration rate (eGFR) on serum levels of
      hepcidin-25 and its isoforms in patients with renal dysfunction. METHODS: Serum
      levels of the biologically active hepcidin-25 and its isoforms were determined in
      CKD and dialysis patients by a mass spectrometry-based assay. RESULTS: In 83
      patients with CKD not requiring dialysis, serum hepcidin-25 levels were not
      significantly increased (5.1 nM versus 4.2 nM, P = 0.30) and positively
      correlated with ferritin (r = 0.74, P < 0.01). Multiple regression analysis
      showed ferritin to be the only significant predictor of hepcidin-25 levels. Serum
      hepcidin-25 levels were not dependent on eGFR. In contrast, hepcidin-20 and total
      hepcidin levels showed an independent significant inverse correlation with eGFR.
      In 48 haemodialysis patients, median hepcidin-25 levels were significantly higher
      than in CKD patients (9.4 nM versus 5.1 nM, P < 0.001) and again strongly
      correlated with ferritin (r = 0.79, P < 0.001). CONCLUSIONS: eGFR is not a major
      determinant of serum hepcidin-25 levels. In contrast, the hepcidin isoforms
      hepcidin-20 and hepcidin-22 accumulate in patients with renal impairment.

PMID- 19854846
TI  - Is therapy of people with chronic kidney disease ONTARGET?

PMID- 19854847
TI  - Use of spent dialysate analysis to estimate blood levels of uraemic solutes
      without blood sampling: urea.
AB  - BACKGROUND: Urea kinetic modelling-based methods are widely used to assess
      dialysis efficacy. However, they require blood sampling and are susceptible to a
      number of errors, mainly from the calculated parameters (particularly V). Spent
      dialysate determinations have been used and have been shown to be reliable and
      simple to use. In this study, we associated dialysate-based and clearance
      determinations along with Kt/V to estimate blood urea levels. METHODS: Urea
      kinetic modelling, continuous sampling of spent dialysate and ionic dialysance
      were determined in 18 stable dialysis patients during 126 dialysis sessions. Mean
      blood urea levels were estimated as follows: mean urea level = spent dialysate -
      urea mass/(dialysance T). Blood urea levels before and after dialysis were
      calculated based on the same determinations and extended formulae. RESULTS:
      Estimated mean urea level was significantly correlated with measured mean blood
      urea level (R(2) = 0.957; P < 0.0001), and Bland and Altman analysis showed
      significant agreement between estimated and measured levels. Estimated and
      measured blood urea levels were also correlated before and after dialysis (R(2) =
      0.972 , P < 0.0001 and R(2) = 0.903 , P < 0.0001, respectively), with good
      agreement for both blood urea before and after dialysis and their respective
      estimates. CONCLUSIONS: Blood urea levels may be reliably estimated from the
      total mass of urea removed in the dialysate and the dialysance measured during
      dialysis. Coupling both measurements allows a precise monitoring of dialysis
      efficacy and a specific evaluation of the patient's urea metabolism status.
      Technical dysfunctions and patient variations may be easily identified using this
      approach without blood sampling.

PMID- 19854848
TI  - Dominance of traditional cardiovascular risk factors over renal function in
      predicting arterial stiffness in subjects with chronic kidney disease.
AB  - BACKGROUND: The predictors of arterial stiffness across the spectrum of renal
      function are unclear. These predictors were investigated across a wide range of
      estimated glomerular filtration rates (eGFR). METHODS: Carotid-femoral pulse wave
      velocity (PWV; an index of arterial stiffness) was measured in 264 subjects with
      chronic kidney disease (CKD) stages 3-5 from three nephrology clinics ('lower GFR
      group'). PWV was also measured in 149 subjects without previously recognized CKD
      ('higher GFR group') including n = 26 with eGFR between 30 and 60 ml/min/1.73
      m(2) and n = 123 with eGFR between 60 and 100 ml/min/1.73 m(2). The association
      between PWV and eGFR was investigated using linear regression. RESULTS: The 413
      subjects had a mean age of 61.9 years, were 51% male, 28% diabetic and 79%
      hypertensive. In age-adjusted analyses within the 'lower GFR group', 'higher GFR
      group' and combined group, PWV correlated with higher systolic blood pressure
      (SBP), pulse pressure (PP), diabetes mellitus, body mass index (BMI) and resting
      heart rate (all P < 0.0008). In addition, PWV correlated inversely with eGFR in
      the 'higher GFR group' (P = 0.03) and combined group (P < 0.0001). In
      multivariable regression analyses of the combined group (n = 413), PWV was
      independently predicted by eGFR (P < 0.05). However, eGFR explained at most 4% of
      the variability in PWV in age-adjusted analyses (compared with 13-15% explained
      by SBP, PP or diabetes) and <1% of PWV variability in models adjusting for age,
      SBP, diabetes, heart rate and BMI (P < 0.0001). CONCLUSION: Although eGFR may
      independently predict PWV, the contribution of GFR per se does not appear to be
      clinically meaningful when compared with traditional cardiovascular risk factors.

PMID- 19854849
TI  - X-inactivation modifies disease severity in female carriers of murine X-linked
      Alport syndrome.
AB  - BACKGROUND: Female carriers of X-linked Alport syndrome (XLAS) demonstrate
      variability in clinical phenotype that, unlike males, cannot be correlated with
      genotype. X-inactivation, the method by which females (XX) silence transcription
      from one X chromosome in order to achieve gene dosage parity with males (XY),
      likely modifies the carrier phenotype, but this hypothesis has not been tested
      directly. METHODS: Using a genetically defined mouse model of XLAS, we generated
      two groups of Alport female (Col4a5(+/-)) carriers that differed only in the X
      controlling element (Xce) allele regulating X-inactivation. We followed the
      groups as far as 6 months of age comparing survival and surrogate outcome
      measures of urine protein and plasma urea nitrogen. RESULTS: Preferential
      inactivation of the mutant Col4a5 gene improved survival and surrogate outcome
      measures of urine protein and plasma urea nitrogen. In studies of surviving mice,
      we found that X-inactivation in kidney, measured by allele-specific mRNA
      expression assays, correlated with surrogate outcomes. CONCLUSIONS: Our findings
      establish X-inactivation as a major modifier of the carrier phenotype in X-linked
      Alport syndrome. Thus, X-inactivation patterns may offer prognostic information
      and point to possible treatment strategies for symptomatic carriers.

PMID- 19854850
TI  - Early ultrasound to detect complications after renal biopsy.

PMID- 19854851
TI  - Glucose tolerance before and after renal transplantation.
AB  - BACKGROUND: Renal insufficiency predisposes to insulin resistance,
      hyperparathyroidism and derangements in calcium phosphate and nitrogenous
      compound balance, leading to pre-transplant hyperglycaemia. These metabolic risk
      factors are not fully corrected after renal transplantation. The present study
      aimed to assess the role of pre-transplant glycaemia and the named metabolic risk
      factors in post-transplant hyperglycaemia [PHYG; impaired fasting glucose (IFG),
      impaired glucose tolerance (IGT) or diabetes mellitus (DM)]. METHODS: This is a
      retrospective cohort study involving 301 patients without pre-transplant DM.
      Measurements included a pre- and post-transplant oral glucose tolerance test
      (OGTT) as well as glomerular filtration rate (GFR), parathyroid hormone (PTH),
      phosphate, calcium and urea measured 10 weeks post-transplant. The risk of PHYG
      at 10 weeks post-transplant was analysed using multiple logistic regression.
      RESULTS: Ninety-three patients (31%) had PHYG (two IFG, 52 IGT, 39 DM). Variables
      associated with PHYG included pre-transplant 2-h glycaemia [OR 1.26, 95% CI
      (1.09, 1.46)] and post-transplant urea levels [OR 1.14, 95% CI (1.02, 1.27)].
      Older age, non-Caucasian ethnicity, previous transplants, >or=3 HLA class 1
      mismatches and high prednisolone doses were likewise associated with an increased
      PHYG risk (all P < 0.05). CONCLUSIONS: Pre-transplant glycaemia and high post
      transplant levels of urea were associated with a greater risk of PHYG. This
      seemed to be independent of GFR, PTH, phosphate, calcium and traditional risk
      factors such as age and glucocorticoid load.

PMID- 19854852
TI  - The endogenous modulators of Ca2+-Mg2+-dependent ATPase in children with chronic
      kidney disease (CKD).
AB  - BACKGROUND: Calcium homeostasis is disturbed in many ways in the course of
      chronic kidney disease (CKD). The concentration of free cytoplasmic calcium in
      erythrocytes is increased. Maintenance of a high concentration gradient (between
      the cystoplasmic and extracellular space) is possible only due to a finely tuned
      cooperation between many regulating systems in the cytoplasmic membranes and cell
      organelles. The aim of our study was to evaluate the activity of Ca(2+)-Mg(2+)
      dependent ATPase (PMCA), calmodulin and calpain-calpastatin (CANP-CAST) system in
      erythrocytes of CKD children treated conservatively in the stages II-IV. METHODS:
      A total of 36 patients with CKD were enrolled in the study. Group A contained
      patients with CKD stage II; group B with CKD stage III; and group C with CKD
      stage IV. The control group D consisted of 30 healthy subjects. In the serum, we
      determined the following: intact parathormon, total calcium, creatinine; in the
      red blood cells: free cytosolic calcium concentration (Ca(i)(2+)), activity of
      Ca(2+)-Mg(2+)-transporting ATPase (PMCA), basal PMCA (bPMCA), calmodulin (CALM),
      CANP, CAST. RESULTS: In all groups, Ca(i)(2+) concentrations were significantly
      higher, whereas PMCA and bPMCA activity were lower than in the controls. CANP
      concentrations in group A were elevated compared to the controls, whereas in
      groups B and C they were significantly lower. In group C, the mean CAST activity
      reached the highest values. CALM concentrations were decreased versus controls in
      all groups of patients. CONCLUSIONS: The intracellular Ca(i)(2+) homeostasis is
      disturbed in children with CKD and aggravates the deterioration of renal function
      as well. The reasons for the progressing increase of erythrocyte calcium
      concentration are multifactorial. Undoubtedly, the decreased PMCA activity, the
      calmodulin deficiency and the dysregulated CANP-CAST system are responsible for
      that phenomenon. The impact of many other biological modulators, creating a
      network defending the cell against the calcium accumulation, cannot be excluded.

PMID- 19854853
TI  - Analysis of critical situations in the evaluation of human exposure to magnetic
      fields with complex waveforms.
AB  - The paper analyses some critical situations in the assessment of the compliance
      with the human exposure limits to the low-frequency magnetic fields. The study is
      focused on non-sinusoidal and transient waveforms in the frequency range from 8
      Hz to 65 kHz. It is carried out by combining measurements and numerical
      evaluations, starting from actual magnetic flux density behaviours. The results
      show that inconsistent indications of compliance with the exposure limits may
      arise not only because of the evaluation method adopted, but also as a result of
      the used time or frequency windows in relation to the investigated magnetic field
      waveform.

PMID- 19854854
TI  - A case of early-onset sarcoidosis with a six-base deletion in the NOD2 gene.

PMID- 19854856
TI  - GTP is required for the microtubule catastrophe-inducing activity of MAP200, a
      tobacco homolog of XMAP215.
AB  - Widely conserved among eukaryotes, the microtubule-associated protein 215
      (MAP215) family enhances microtubule dynamic instability. The family member
      studied most extensively, Xenopus laevis XMAP215, has been reported to enhance
      both assembly and disassembly parameters, although the mechanism whereby one
      protein can exert these apparently contradictory effects has not been clarified.
      Here, we analyze the activity of a plant MAP215 homolog, tobacco (Nicotiana
      tabacum) MAP200 on microtubule behavior in vitro. We show that, like XMAP215,
      MAP200 promotes both assembly and disassembly parameters, including microtubule
      growth rate and catastrophe frequency. When MAP200 is added to tubulin and taxol,
      strikingly long-coiled structures form. When GDP partially replaces GTP, the
      increase of catastrophe frequency by MAP200 is strongly diminished, even though
      this replacement stimulates catastrophe in the absence of MAP200. This implies
      that MAP200 induces catastrophes by a specific, GTP-requiring pathway. We
      hypothesize that, in the presence of MAP200, a catastrophe-prone microtubule
      lattice forms occasionally when elongated but nonadjacent protofilaments make
      lateral contacts.

PMID- 19854855
TI  - Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor.
AB  - RA is a chronic, debilitating disease in which articular inflammation and joint
      destruction are accompanied by systemic manifestations including anaemia, fatigue
      and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is
      thought to mediate many of the local and systemic effects of this disease. Unlike
      a number of other cytokines, IL-6 can activate cells through both membrane-bound
      (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types
      responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the
      sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal
      transduction, has been found to play a key role in acute and chronic
      inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can
      increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can
      stimulate pannus development through increased VEGF expression and increase bone
      resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit
      through conventional or trans-signalling, include regulation of acute-phase
      protein synthesis, as well as hepcidin production and stimulation of the
      hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to
      anaemia and fatigue, respectively. This review aims to provide an insight into
      the biological effects of IL-6 in RA, examining how IL-6 can induce the articular
      and systemic effects of this disease.

PMID- 19854857
TI  - An ABC transporter mutation alters root exudation of phytochemicals that provoke
      an overhaul of natural soil microbiota.
AB  - Root exudates influence the surrounding soil microbial community, and recent
      evidence demonstrates the involvement of ATP-binding cassette (ABC) transporters
      in root secretion of phytochemicals. In this study, we examined effects of seven
      Arabidopsis (Arabidopsis thaliana) ABC transporter mutants on the microbial
      community in native soils. After two generations, only the Arabidopsis abcg30
      (Atpdr2) mutant had significantly altered both the fungal and bacterial
      communities compared with the wild type using automated ribosomal intergenic
      spacer analysis. Similarly, root exudate profiles differed between the mutants;
      however, the largest variance from the wild type (Columbia-0) was observed in
      abcg30, which showed increased phenolics and decreased sugars. In support of this
      biochemical observation, whole-genome expression analyses of abcg30 roots
      revealed that some genes involved in biosynthesis and transport of secondary
      metabolites were up-regulated, while some sugar transporters were down-regulated
      compared with genome expression in wild-type roots. Microbial taxa associated
      with Columbia-0 and abcg30 cultured soils determined by pyrosequencing revealed
      that exudates from abcg30 cultivated a microbial community with a relatively
      greater abundance of potentially beneficial bacteria (i.e. plant-growth-promoting
      rhizobacteria and nitrogen fixers) and were specifically enriched in bacteria
      involved in heavy metal remediation. In summary, we report how a single gene
      mutation from a functional plant mutant influences the surrounding community of
      soil organisms, showing that genes are not only important for intrinsic plant
      physiology but also for the interactions with the surrounding community of
      organisms as well.

PMID- 19854858
TI  - Uncovering small RNA-mediated responses to phosphate deficiency in Arabidopsis by
      deep sequencing.
AB  - Recent studies have demonstrated the important role of plant microRNAs (miRNAs)
      under nutrient deficiencies. In this study, deep sequencing of Arabidopsis
      (Arabidopsis thaliana) small RNAs was conducted to reveal miRNAs and other small
      RNAs that were differentially expressed in response to phosphate (Pi) deficiency.
      About 3.5 million sequence reads corresponding to 0.6 to 1.2 million unique
      sequence tags from each Pi-sufficient or Pi-deficient root or shoot sample were
      mapped to the Arabidopsis genome. We showed that upon Pi deprivation, the
      expression of miR156, miR399, miR778, miR827, and miR2111 was induced, whereas
      the expression of miR169, miR395, and miR398 was repressed. We found cross talk
      coordinated by these miRNAs under different nutrient deficiencies. In addition to
      miRNAs, we identified one Pi starvation-induced DICER-LIKE1-dependent small RNA
      derived from the long terminal repeat of a retrotransposon and a group of 19
      nucleotide small RNAs corresponding to the 5' end of tRNA and expressed at a high
      level in Pi-starved roots. Importantly, we observed an increased abundance of
      TAS4-derived trans-acting small interfering RNAs (ta-siRNAs) in Pi-deficient
      shoots and uncovered an autoregulatory mechanism of PAP1/MYB75 via miR828 and
      TAS4-siR81(-) that regulates the biosynthesis of anthocyanin. This finding sheds
      light on the regulatory network between miRNA/ta-siRNA and its target gene. Of
      note, a substantial amount of miR399* accumulated under Pi deficiency. Like
      miR399, miR399* can move across the graft junction, implying a potential
      biological role for miR399*. This study represents a comprehensive expression
      profiling of Pi-responsive small RNAs and advances our understanding of the
      regulation of Pi homeostasis mediated by small RNAs.

PMID- 19854859
TI  - The ectomycorrhizal fungus Laccaria bicolor stimulates lateral root formation in
      poplar and Arabidopsis through auxin transport and signaling.
AB  - The early phase of the interaction between tree roots and ectomycorrhizal fungi,
      prior to symbiosis establishment, is accompanied by a stimulation of lateral root
      (LR) development. We aimed to identify gene networks that regulate LR development
      during the early signal exchanges between poplar (Populus tremula x Populus alba)
      and the ectomycorrhizal fungus Laccaria bicolor with a focus on auxin transport
      and signaling pathways. Our data demonstrated that increased LR development in
      poplar and Arabidopsis (Arabidopsis thaliana) interacting with L. bicolor is not
      dependent on the ability of the plant to form ectomycorrhizae. LR stimulation
      paralleled an increase in auxin accumulation at root apices. Blocking plant polar
      auxin transport with 1-naphthylphthalamic acid inhibited LR development and auxin
      accumulation. An oligoarray-based transcript profile of poplar roots exposed to
      molecules released by L. bicolor revealed the differential expression of 2,945
      genes, including several components of polar auxin transport (PtaPIN and PtaAUX
      genes), auxin conjugation (PtaGH3 genes), and auxin signaling (PtaIAA genes).
      Transcripts of PtaPIN9, the homolog of Arabidopsis AtPIN2, and several PtaIAAs
      accumulated specifically during the early interaction phase. Expression of these
      rapidly induced genes was repressed by 1-naphthylphthalamic acid. Accordingly, LR
      stimulation upon contact with L. bicolor in Arabidopsis transgenic plants
      defective in homologs of these genes was decreased or absent. Furthermore, in
      Arabidopsis pin2, the root apical auxin increase during contact with the fungus
      was modified. We propose a model in which fungus-induced auxin accumulation at
      the root apex stimulates LR formation through a mechanism involving PtaPIN9
      dependent auxin redistribution together with PtaIAA-based auxin signaling.

PMID- 19854860
TI  - Distal expression of knotted1 in maize leaves leads to reestablishment of
      proximal/distal patterning and leaf dissection.
AB  - Maize (Zea mays) leaves provide a useful system to study how proximal/distal
      patterning is established because of the distinct tissues found in the distal
      blade and the proximal sheath. Several mutants disrupt this pattern, including
      the dominant knotted1-like homeobox (knox) mutants. knox genes encode homeodomain
      proteins of the TALE superclass of transcription factors. Class I knox genes are
      expressed in the meristem and down-regulated as leaves initiate. Gain-of-function
      phenotypes result from misexpression in leaves. We identified a new dominant
      allele of maize knotted1, Kn1-DL, which contains a transposon insertion in the
      promoter in addition to a tandem duplication of the kn1 locus. In situ
      hybridization shows that kn1 is misexpressed in two different parts of the blade
      that correlate with the different phenotypes observed. When kn1 is misexpressed
      along the margins, flaps of sheath-like tissue form along the margins. Expression
      in the distal tip leads to premature termination of the midrib into a knot and
      leaf bifurcation. The gain-of-function phenotypes suggest that kn1 establishes
      proximal/distal patterning when expressed in distal locations and lead to the
      hypothesis that kn1 normally participates in the establishment of proximal/distal
      polarity in the incipient leaf.

PMID- 19854861
TI  - Dominance of CTX-M-2 and CTX-M-56 among extended-spectrum beta-lactamases
      produced by Klebsiella pneumoniae and Escherichia coli isolated in hospitals in
      Paraguay.

PMID- 19854862
TI  - In vitro activities of antifungal drugs against Rhinocladiella mackenziei, an
      agent of fatal brain infection.

PMID- 19854863
TI  - Metabolism and circadian rhythms--implications for obesity.
AB  - Obesity has become a serious public health problem and a major risk factor for
      the development of illnesses, such as insulin resistance and hypertension. Human
      homeostatic systems have adapted to daily changes in light and dark in a way that
      the body anticipates the sleep and activity periods. Mammals have developed an
      endogenous circadian clock located in the suprachiasmatic nuclei of the anterior
      hypothalamus that responds to the environmental light-dark cycle. Similar clocks
      have been found in peripheral tissues, such as the liver, intestine, and adipose
      tissue, regulating cellular and physiological functions. The circadian clock has
      been reported to regulate metabolism and energy homeostasis in the liver and
      other peripheral tissues. This is achieved by mediating the expression and/or
      activity of certain metabolic enzymes and transport systems. In return, key
      metabolic enzymes and transcription activators interact with and affect the core
      clock mechanism. In addition, the core clock mechanism has been shown to be
      linked with lipogenic and adipogenic pathways. Animals with mutations in clock
      genes that disrupt cellular rhythmicity have provided evidence for the
      relationship between the circadian clock and metabolic homeostasis. In addition,
      clinical studies in shift workers and obese patients accentuate the link between
      the circadian clock and metabolism. This review will focus on the interconnection
      between the circadian clock and metabolism, with implications for obesity and how
      the circadian clock is influenced by hormones, nutrients, and timed meals.

PMID- 19854864
TI  - A novel synthetic androgen receptor ligand, S42, works as a selective androgen
      receptor modulator and possesses metabolic effects with little impact on the
      prostate.
AB  - We identified a novel synthetic steroid, S42, as a promising candidate of
      selective androgen receptor (AR) modulator. Results of the whole-cell binding
      assay using COS-7 cells exogenously expressing various steroid receptors
      indicated that S42 specifically binds to AR and progesterone receptor. When
      orchiectomized Sprague Dawley rats were administered with S42 for 3 wk, the
      muscle weight of the levator ani was increased as markedly as that induced by
      5alpha-dihydrotestosterone (DHT), but the weight of the prostate was not elevated
      at any doses in contrast to DHT. The plasma concentrations of gonadotropin and
      adiponectin, those down-regulated by DHT, were unaffected by S42. In addition,
      although the plasma triglyceride level was unaffected by DHT, it was
      significantly reduced by S42. This effect of S42 was associated with suppression
      of the SRBP-1c-mediated lipogenic and insulin-desensitizing pathway in the liver
      and visceral fat. Taken together, S42 works as an AR agonist in muscle and as an
      AR antagonist in the prostate, pituitary gland, and liver, accompanying
      beneficial potentials on lipid metabolism.

PMID- 19854865
TI  - Thyroid hormone effects on whole-body energy homeostasis and tissue-specific
      fatty acid uptake in vivo.
AB  - The effects of thyroid hormone (TH) status on energy metabolism and tissue
      specific substrate supply in vivo are incompletely understood. To study the
      effects of TH status on energy metabolism and tissue-specific fatty acid (FA)
      fluxes, we used metabolic cages as well as (14)C-labeled FA and (3)H-labeled
      triglyceride (TG) infusion in rats treated with methimazole and either 0
      (hypothyroidism), 1.5 (euthyroidism), or 16.0 (thyrotoxicosis) microg per 100 g/d
      T(4) for 11 d. Thyrotoxicosis increased total energy expenditure by 38% (P =
      0.02), resting energy expenditure by 61% (P = 0.002), and food intake by 18% (P =
      0.004). Hypothyroidism tended to decrease total energy expenditure (10%; P =
      0.064) and resting energy expenditure (12%; P = 0.025) but did not affect food
      intake. TH status did not affect spontaneous physical activity. Thyrotoxicosis
      increased fat oxidation (P = 0.006), whereas hypothyroidism decreased glucose
      oxidation (P = 0.035). Plasma FA concentration was increased in thyrotoxic but
      not hypothyroid rats. Thyrotoxicosis increased albumin-bound FA uptake in muscle
      and white adipose tissue (WAT), whereas hypothyroidism had no effect in any
      tissue studied, suggesting mass-driven albumin-bound FA uptake. During
      thyrotoxicosis, TG-derived FA uptake was increased in muscle and heart,
      unaffected in WAT, and decreased in brown adipose tissue. Conversely, during
      hypothyroidism TG-derived FA uptake was increased in WAT in association with
      increased lipoprotein lipase activity but unaffected in oxidative tissues and
      decreased in liver. In conclusion, TH status determines energy expenditure
      independently of spontaneous physical activity. The changes in whole-body lipid
      metabolism are accompanied by tissue-specific changes in TG-derived FA uptake in
      accordance with hyper- and hypometabolic states induced by thyrotoxicosis and
      hypothyroidism, respectively.

PMID- 19854866
TI  - Transgenic mice expressing green fluorescent protein under the control of the
      corticotropin-releasing hormone promoter.
AB  - CRH is widely expressed in the brain and is of broad functional relevance to a
      number of physiological processes, including stress response, parturition, immune
      response, and ingestive behavior. To delineate further the organization of the
      central CRH network, we generated mice expressing green fluorescent protein (GFP)
      under the control of the CRH promoter, using bacterial artificial chromosome
      technology. Here we validate CRH-GFP transgene expression within specific brain
      regions and confirm the distribution of central GFP-producing cells to faithfully
      recapitulate that of CRH-expressing cells. Furthermore, we confirm the functional
      integrity of a population of GFP-producing cells by demonstrating their opposite
      responsiveness to nutritional status. We anticipate that this transgenic model
      will lend itself as a highly tractable tool for the investigation of CRH
      expression and function in discrete brain regions.

PMID- 19854867
TI  - Water adaptation strategy in anuran amphibians: molecular diversity of aquaporin.
AB  - Most adult anuran amphibians except for the aquatic species absorb water across
      the ventral pelvic skin and reabsorb it from urine in the urinary bladder. Many
      terrestrial and arboreal species use a region in the posterior or pelvic region
      of the ventral skin that is specialized for rapid rehydration from shallow water
      sources or moist substrates. Periods of terrestrial activity can be prolonged by
      reabsorption of dilute urine from the urinary bladder. Aquaporin (AQP), a water
      channel protein, plays a fundamental role in these water absorption/reabsorption
      processes, which are regulated by antidiuretic hormone. Characterization of AQPs
      from various anurans revealed that the unique water homeostasis is basically
      mediated by two types of anuran-specific AQPs, i.e. ventral pelvic skin and
      urinary bladder type, respectively. The bladder-type AQP is further expressed in
      the pelvic skin of terrestrial and arboreal species, together with the pelvic
      skin-type AQP. In contrast, the pelvic skin-type AQP (AQP-x3) of the aquatic
      Xenopus has lost the ability of efficient protein production. The extra C
      terminal tail in AQP-x3 consisting of 33 nucleotides within the coding region
      appears to participate in the posttranscriptional regulation of AQP-x3 gene
      expression by attenuating protein expression. The positive transcriptional
      regulation of bladder-type AQP in the pelvic skin and negative
      posttranscriptional regulation of pelvic skin-type AQP provide flexibility in the
      water regulation mechanisms, which might have contributed to the evolutionary
      adaptation of anurans to a wide variety of water environments.

PMID- 19854868
TI  - Hypothalamic and hindbrain melanocortin receptors contribute to the feeding,
      thermogenic, and cardiovascular action of melanocortins.
AB  - Forebrain ventricular delivery of melanocortin receptor (MC3/4R) agonist
      increases energy expenditure and decreases food intake (FI). Because forebrain
      ventricular delivery provides ligand to various anatomically distributed MC3/4R
      bearing nuclei, it is unclear which of the receptor subpopulations contributes to
      the feeding suppression and the sympathetic-thermogenic effects observed. The
      literature indicates that reexpression of MC4R in the paraventricular nucleus
      (PVH) affects the feeding but not the energetic phenotype of the MC4R knockout,
      suggesting that divergent MC4R populations mediate energy expenditure (hindbrain)
      and FI (hypothalamus) effects of stimulation. Not consistent with this view are
      data indicating that PVH sympathetic projection neurons express MC4Rs and that
      feeding effects are induced from hindbrain MC4R sites. Therefore, we hypothesize
      an opposing perspective: that stimulation of anatomically diverse MC3/4R-bearing
      nuclei triggers energetic as well as feeding effects. To test this hypothesis,
      ventricle subthreshold doses of MC3/4R agonist (5 and 10 pmol) were applied in
      separate experiments to six hindbrain and hypothalamic sites; core temperature
      (Tc), heart rate (HR), spontaneous activity (SPA), and FI were measured in
      behaving rats. Nucleus tractus solitarius and PVH stimulation increased Tc, HR,
      and SPA and decreased FI. Rostral ventrolateral medulla, parabrachial nucleus,
      and retrochiasmatic area stimulation increased Tc, HR, but not SPA, and decreased
      FI. The response profile differed to some extent for each nucleus tested,
      suggesting differential output circuitries for the measured parameters. Data are
      consistent with the view that energetic and feeding responses are not controlled
      by regionally divergent MC3/4Rs and can be elicited from multiple, anatomically
      distributed MC3/4R populations.

PMID- 19854869
TI  - Poly(Adenosine 5'-diphosphate-ribose) polymerase inhibition counteracts multiple
      manifestations of experimental type 1 diabetic nephropathy.
AB  - This study was aimed at evaluating the role for poly(ADP-ribose) polymerase
      (PARP) in early nephropathy associated with type 1 diabetes. Control and
      streptozotocin-diabetic rats were maintained with or without treatment with one
      of two structurally unrelated PARP inhibitors, 1,5-isoquinolinediol (ISO) and 10
      (4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de] anthracen-3-one (GPI
      15427), at 3 mg/kg(-1) x d(-1) ip and 30 mg/kg(-1) x d(-1), respectively, for 10
      wk after the first 2 wk without treatment. PARP activity in the renal cortex was
      assessed by immunohistochemistry and Western blot analysis of poly(ADP
      ribosyl)ated proteins. Variables of diabetic nephropathy in urine and renal
      cortex were evaluated by ELISA, Western blot analysis, immunohistochemistry, and
      colorimetry. Urinary albumin excretion was increased about 4-fold in diabetic
      rats, and this increase was prevented by ISO and GPI-15427. PARP inhibition
      counteracted diabetes-associated increase in poly(ADP-ribose) immunoreactivities
      in renal glomeruli and tubuli and poly(ADP-ribosyl)ated protein level. Renal
      concentrations of TGF-beta(1), vascular endothelial growth factor, endothelin-1,
      TNF-alpha, monocyte chemoattractant protein-1, lipid peroxidation products, and
      nitrotyrosine were increased in diabetic rats, and all these changes as well as
      an increase in urinary TNF-alpha excretion were completely or partially prevented
      by ISO and GPI-15427. PARP inhibition counteracted diabetes-induced up-regulation
      of endothelin (B) receptor, podocyte loss, accumulation of collagen-alpha1 (IY),
      periodic acid-Schiff-positive substances, fibronectin, and advanced glycation end
      products in the renal cortex. In conclusion, PARP activation is implicated in
      multiple changes characteristic for early nephropathy associated with type 1
      diabetes. These findings provide rationale for development and further studies of
      PARP inhibitors and PARP inhibitor-containing combination therapies.

PMID- 19854870
TI  - Tandem KH domains of Khd4 recognize AUACCC and are essential for regulation of
      morphology as well as pathogenicity in Ustilago maydis.
AB  - RNA-binding proteins constitute key factors of the post-transcriptional
      machinery. These regulatory proteins recognize specific elements within target
      transcripts to promote, for example, maturation, translation, or stability of
      mRNAs. In Ustilago maydis, evidence is accumulating that post-transcriptional
      processes are important to determine pathogenicity. Deletion of khd4, encoding a
      predicted RNA-binding protein with five K homology (KH) domains, causes aberrant
      cell morphology and reduced virulence. Here, we demonstrate that Khd4 recognizes
      the sequence AUACCC in vivo via its tandem KH domains 3 and 4. This sequence most
      likely functions as a regulatory RNA element in U. maydis, since it accumulates
      in 3' untranslated regions. Consistently, an independent mRNA expression
      profiling approach revealed that the binding motif is significantly enriched in
      transcripts showing altered expression levels in khd4Delta strains. Since the
      vast majority of potential Khd4 target mRNAs exhibit increased amounts in
      deletion mutants, Khd4 might promote mRNA instability. Mutants that fail to bind
      AUACCC resemble deletion mutants, which exhibit altered cell morphology,
      disturbed filamentous growth, and severely reduced virulence. Hence, RNA binding
      is essential for function of Khd4, stressing the importance of post
      transcriptional control in regulating morphology and pathogenicity.

PMID- 19854873
TI  - Caldithrix palaeochoryensis sp. nov., a thermophilic, anaerobic, chemo
      organotrophic bacterium from a geothermally heated sediment, and emended
      description of the genus Caldithrix.
AB  - A novel thermophilic, strictly anaerobic, chemo-organotrophic bacterium,
      designated MC(T), was isolated from a geothermally heated sediment of a marine
      hydrothermal system at Palaeochory Bay, Milos, Greece. Cells of strain MC(T) were
      rods of variable length (4-12 mum) and width (0.2-0.3 mum), occurring as single
      cells or forming large aggregates that were visible as flocs. Strain MC(T) grew
      optimally at pH 7.0 and 60 degrees C and with 3 % (w/v) NaCl. Strain MC(T) grew
      chemo-organoheterotrophically and fermented peptides and di- and polysaccharides
      in the presence of 0.1 g yeast extract l(-1). The DNA G+C content of strain MC(T)
      was 43.3 mol%. Phylogenetic analysis of the 16S rRNA gene sequence placed strain
      MC(T) within the genus Caldithrix. However, strain MC(T) possessed certain
      phenotypic features that differentiated it from the type strain of the only
      species of the genus Caldithrix described to date. On the basis of phylogenetic
      and phenotypic characteristics, it is proposed that strain MC(T) represents a
      novel species, Caldithrix palaeochoryensis sp. nov. The type strain is MC(T)
      (=DSM 21940(T) =VKM B-2536(T)). In addition, an emended description of the genus
      Caldithrix is presented.

PMID- 19854874
TI  - Haloactinobacterium album gen. nov., sp. nov., a halophilic actinobacterium, and
      proposal of Ruaniaceae fam. nov.
AB  - A Gram-staining-positive, facultatively anaerobic, non-motile and moderately
      halophilic actinobacterium, designated YIM 93306(T), was isolated from a salt
      lake in Xinjiang province, north-west China, and subjected to a polyphasic
      taxonomic study. Strain YIM 93306(T) grew in the presence of 2-16 % (w/v) NaCl
      and did not grow without NaCl. The peptidoglycan type was A4alpha with an l-Lys-l
      Glu interpeptide bridge. The whole-cell sugars were glucosamine, arabinose,
      mannose and two unknown sugars. The predominant menaquinone was MK-8(H(4)). The
      major fatty acids were iso-C(15 : 0), anteiso-C(15 : 0) and anteiso-C(17 : 0).
      The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol, one unknown phosphoglycolipid and one unknown phospholipid.
      The DNA G+C content was 68.3 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain YIM 93306(T) fell within the radius of the
      suborder Micrococcineae. Its closest phylogenetic neighbour was the type strain
      of Ruania albidiflava (AS 4.3142(T); 96.2 % 16S rRNA gene sequence similarity),
      the sole recognized species of the genus Ruania. Sequence similarities between
      strain YIM 93306(T) and members of other genera of the suborder Micrococcineae
      were <95.2 %. On the basis of phylogenetic analysis, phenotypic characteristics
      and chemotaxonomic differences, a novel genus and species, Haloactinobacterium
      album gen. nov., sp. nov., is proposed. The type strain of the species is YIM
      93306(T) (=DSM 21368(T) =KCTC 19413(T) =CCTCC AB 208069(T)). Based on
      phylogenetic characteristics and 16S rRNA gene signature nucleotide patterns, the
      genera Ruania and Haloactinobacterium gen. nov. are proposed to belong to a novel
      family, Ruaniaceae fam. nov.

PMID- 19854872
TI  - Deadenylation of maternal mRNAs mediated by miR-427 in Xenopus laevis embryos.
AB  - We show that microRNA-427 (miR-427) mediates the rapid deadenylation of maternal
      mRNAs after the midblastula transition (MBT) of Xenopus laevis embryogenesis. By
      MBT, the stage when the embryonic cell cycle is remodeled and zygotic
      transcription of mRNAs is initiated, each embryo has accumulated approximately
      10(9) molecules of miR-427 processed from multimeric pri-miR-427 transcripts
      synthesized after fertilization. We demonstrate that the maternal mRNAs for
      cyclins A1 and B2 each contain a single miR-427 target sequence, spanning less
      than 30 nucleotides, that is both necessary and sufficient for deadenylation, and
      that inactivation of miR-427 leads to stabilization of the mRNAs. Although this
      deadenylation normally takes place after MBT, exogenous miRNAs produced
      prematurely in vivo can promote deadenylation prior to MBT, indicating that
      turnover of the maternal mRNAs is limited by the amount of accumulated miR-427.
      Injected transcripts comprised solely of the cyclin mRNA 3' untranslated regions
      or bearing a 5' ApppG cap undergo deadenylation, showing that translation of the
      targeted RNA is not required. miR-427 is not unique in promoting deadenylation,
      as an unrelated miRNA, let-7, can substitute for miR-427 if the reporter RNA
      contains an appropriate let-7 target site. We propose that miR-427, like the
      orthologous miR-430 of zebrafish, functions to down-regulate expression of
      maternal mRNAs early in development.

PMID- 19854871
TI  - Physical and genetic interactions of yeast Cwc21p, an ortholog of human
      SRm300/SRRM2, suggest a role at the catalytic center of the spliceosome.
AB  - In Saccharomyces cerevisiae, Cwc21p is a protein of unknown function that is
      associated with the NineTeen Complex (NTC), a group of proteins involved in
      activating the spliceosome to promote the pre-mRNA splicing reaction. Here, we
      show that Cwc21p binds directly to two key splicing factors-namely, Prp8p and
      Snu114p-and becomes the first NTC-related protein known to dock directly to U5
      snRNP proteins. Using a combination of proteomic techniques we show that the N
      terminus of Prp8p contains an intramolecular fold that is a Snu114p and Cwc21p
      interacting domain (SCwid). Cwc21p also binds directly to the C-terminus of
      Snu114p. Complementary chemical cross-linking experiments reveal reciprocal
      protein footprints between the interacting Prp8 and Cwc21 proteins, identifying
      the conserved cwf21 domain in Cwc21p as a Prp8p binding site. Genetic and
      functional interactions between Cwc21p and Isy1p indicate that they have related
      functions at or prior to the first catalytic step of splicing, and suggest that
      Cwc21p functions at the catalytic center of the spliceosome, possibly in response
      to environmental or metabolic changes. We demonstrate that SRm300, the only SR
      related protein known to be at the core of human catalytic spliceosomes, is a
      functional ortholog of Cwc21p, also interacting directly with Prp8p and Snu114p.
      Thus, the function of Cwc21p is likely conserved from yeast to humans.

PMID- 19854875
TI  - Rhodobacter johrii sp. nov., an endospore-producing cryptic species isolated from
      semi-arid tropical soils.
AB  - An oval to rod-shaped, phototrophic, purple non-sulfur bacterium, strain
      JA192(T), was isolated from an enrichment culture of a pasteurized rhizosphere
      soil sample from a field cultivated with jowar (sorghum) collected from
      Godumakunta village near Hyderabad, India. Strain JA192(T) is Gram-negative,
      motile and produces endospores. Phylogenetic analysis on the basis of 16S rRNA
      gene sequences showed that the strain JA192(T) is closely related to Rhodobacter
      sphaeroides 2.4.1(T) (99.9 % sequence similarity), Rba. megalophilus JA194(T)
      (99.8 %) and Rba. azotoformans KA25(T) (98.1 %) and clusters with other species
      of the genus Rhodobacter of the family Rhodobacteraceae. However, DNA-DNA
      hybridization with Rba. sphaeroides DSM 158(T), Rba. megalophilus JA194(T) and
      Rba. azotoformans JCM 9340(T) showed relatedness of only 38-57 % with respect to
      strain JA192(T). On the basis of 16S rRNA gene sequence analysis, DNA-DNA
      hybridization data and morphological, physiological and chemotaxonomic
      characters, strain JA192(T) represents a novel species of the genus Rhodobacter,
      for which the name Rhodobacter johrii sp. nov. is proposed. The type strain is
      JA192(T) (=DSM 18678(T) =JCM 14543(T) =MTCC 8172(T)).

PMID- 19854876
TI  - Thalassobacillus hwangdonensis sp. nov., isolated from a tidal flat sediment.
AB  - A Gram-staining-positive, endospore-forming, motile, rod-shaped bacterium, strain
      AD-1(T), was isolated from a tidal flat sediment of the coast of Hwangdo on the
      Yellow Sea, Korea. Strain AD-1(T) grew optimally at pH 7.0-7.5 and 40 degrees C
      and in the presence of 5-10 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA
      gene sequences showed that strain AD-1(T) was most closely related to
      Thalassobacillus devorans G-19.1(T) (98.0 % sequence similarity) and
      Thalassobacillus cyri HS286(T) (97.8 %). The cell-wall peptidoglycan was based on
      meso-diaminopimelic acid and MK-7 was the predominant menaquinone. The major
      polar lipids were diphosphatidylglycerol, phosphatidylglycerol and two
      unidentified lipids. The major fatty acids (>10 % of total fatty acids) were iso
      C(15 : 0), iso-C(17 : 0) and anteiso-C(15 : 0). The DNA G+C content of strain AD
      1(T) was 45.2 mol%. It appears reasonable to classify strain AD-1(T) as a member
      of the genus Thalassobacillus. There were differences in fatty acid profiles and
      phenotypic and genetic characteristics between strain AD-1(T) and the type
      strains of the two Thalassobacillus species. On the basis of the data presented,
      strain AD-1(T) represents a novel species within the genus Thalassobacillus, for
      which the name Thalassobacillus hwangdonensis sp. nov. is proposed. The type
      strain is AD-1(T) (=KCTC 13254(T) =CCUG 56607(T)).

PMID- 19854877
TI  - Pseudomonas taiwanensis sp. nov., isolated from soil.
AB  - A novel Gram-negative, rod-shaped, motile, non-spore-forming bacterial strain,
      CMS(T), isolated from soil was characterized using phenotypic and molecular
      taxonomic methods. 16S rRNA gene sequence analysis revealed that the organism
      belongs phylogenetically to the genus Pseudomonas. Pseudomonas monteilii, P.
      plecoglossicida and P. mosselii were the most closely related species, with 16S
      rRNA gene sequence similarities to the respective type strains of 99.79, 99.73
      and 99.59 %. Relatively low gyrB gene sequence similarities (<90 %) and DNA-DNA
      reassociation values (<51 %) were obtained between the strain and its
      phylogenetically closest neighbours. The G+C content of strain CMS(T) was 62.7
      mol%. The major cellular fatty acids were C(18 : 1) omega 7c, summed feature 3
      (C(16 : 1) omega 7c and/or iso-C(15 : 0) 2-OH), C(16 : 0) and C(10 : 0) 3-OH.
      Based on the phenotypic and genetic evidence, the strain is suggested to
      represent a novel species, for which the name Pseudomonas taiwanensis sp. nov. is
      proposed. The type strain is CMS(T) (=BCRC 17751(T) =DSM 21245(T)).

PMID- 19854878
TI  - Halopelagius inordinatus gen. nov., sp. nov., a new member of the family
      Halobacteriaceae isolated from a marine solar saltern.
AB  - Two extremely halophilic archaea, strains RO5-2(T) and RO5-14, were isolated from
      Rudong marine solar saltern in Jiangsu, China. Cells of the two strains were
      pleomorphic, motile and stained Gram-negative. Colonies were red-pigmented.
      Strains RO5-2(T) and RO5-14 were able to grow at 20-50 degrees C (optimum 37
      degrees C), at 2.6-4.8 M NaCl (optimum 3.4-3.9 M NaCl), at 0.03-0.7 M MgCl(2)
      (optimum 0.5 M MgCl(2)) and at pH 5.5-8.0 (optimum pH 6.5-7.0). Cells lyse in
      distilled water and the minimal NaCl concentration to prevent cell lysis was 12 %
      (w/v). The major polar lipids of the two strains were phosphatidylglycerol,
      phosphatidylglycerol phosphate methyl ester and two major glycolipids
      chromatographically identical to sulfated mannosyl glucosyl diether (S-DGD-1) and
      mannosyl glucosyl diether (DGD-1). The 16S rRNA gene sequences of strains RO5
      2(T) and RO5-14 showed 93.4-93.8 % similarity to the closest cultivated relative,
      Halosarcina pallida. The DNA G+C content of strains RO5-2(T) and RO5-14 was 61.0
      mol% and 59.9 mol%, respectively. The DNA-DNA relatedness between strains RO5
      2(T) and RO5-14 was 86.0 %. The phenotypic, chemotaxonomic and phylogenetic
      properties suggest that strains RO5-2(T) and RO5-14 represent a novel species in
      a new genus within the family Halobacteriaceae, for which the name Halopelagius
      inordinatus gen. nov., sp. nov. is proposed. The type strain is RO5-2(T) (=CGMCC
      1.7739(T) =JCM 15773(T)).

PMID- 19854879
TI  - Convictions for sexual transmission of diseases do not enhance autonomy.
      [corrected].

PMID- 19854880
TI  - Increasing HIV testing in general practice: brief advice seems to work.

PMID- 19854881
TI  - Hepatitis C screening in genitourinary clinic attendees.

PMID- 19854882
TI  - Questioning the value of screening for gonorrhoea in symptomless heterosexual
      men.
AB  - These two papers discuss whether gonorrhoea screening of asymptomatic
      heterosexual men with no contact history should continue in UK genitourinary
      medicine clinics. Currently, most clinics routinely test all attenders. This
      requires an estimated 330,000 tests annually to detect 915 positives (1 in 361).
      The benefits to these patients are uncertain but the costs are huge and could
      fund currently unprovided services such as oral contraceptive provision or HIV
      testing before terminations of pregnancy. However stopping testing would deny
      individuals the reassurance they seek, prevent early detection of outbreaks and
      fail to detect carriers who go on to cause morbidity in their partners. On this
      view, the availability of non-invasive tests should be used to widen screening.

PMID- 19854883
TI  - Nurse-led sexually transmitted disease clinics: staff perceptions concerning the
      quality of the service.
AB  - The aim of this study was to evaluate staff perception of a nurse-led sexually
      transmitted infection (STI) clinical service. The staff at the Amsterdam STI
      clinic were interviewed using a standardized questionnaire. A series of eight
      questions was designed to determine the perceived advantages or disadvantages of
      nurse-led clinics, based on personal experience, using a Likert scale. After
      completion of the structured interview, the staff were offered the opportunity of
      providing comments. All 36 members of staff completed the survey. Twenty-seven
      (75%) agreed or strongly agreed that nurse-led clinics provided more time with
      patients. Sixty-four percent agreed or strongly agreed that such a service
      provided greater confidentiality and 94% agreed or strongly agreed that 'nurse
      led clinics provided a high level of job satisfaction for nurses.' In contrast,
      only 64% agreed or strongly agreed that nurse-led clinics provided a high level
      of job satisfaction for doctors. When staff comments were evaluated, four common
      themes emerged. First, that this was an efficient way of providing services;
      second, that the clinic was a pleasant environment, there was excellent teamwork
      and greater job satisfaction; third, that a good deal of rivalry existed between
      doctors and nurses and finally, that there was a need for and importance of
      protocols, rules and staff training and development. In conclusion, there was a
      high level of staff satisfaction with the service. Nurse-led STI clinics may be a
      useful adjunct to existing STI facilities.

PMID- 19854884
TI  - Use of two HIV-POCT tests to identify false reactives.

PMID- 19854885
TI  - Condom use and prevalence of sexually transmitted infection among performers in
      the adult entertainment industry.

PMID- 19854886
TI  - Current management of syphilis infection.

PMID- 19854887
TI  - Destigmatizing genitourinary medicine and sexually transmitted infections in the
      UK.
AB  - Sexually transmitted infections (STIs) and the clinics patients attend for STI
      management remain stigmatized. Although emphasizing sexual intercourse rather
      than sexual behaviour as an important factor in STI acquisition may help to
      destigmatize STIs, this will require a change in the national mindset. A
      different approach entails destigmatizing genitourinary (GU) medicine/sexual
      health thereby normalizing the conditions managed in these settings. This may be
      helped by emphasizing the non-STI-related aspect of GU medicine and by
      considering a change in terminology that removes the focus from STIs and attempts
      to absorb the term into the broader category of genital infection.

PMID- 19854888
TI  - Assessment of the toxicity of hydralazine in the rat using an ultrasensitive flow
      based cardiac troponin I immunoassay.
AB  - The purpose of this study was to correlate the histologic changes in the heart to
      serum cardiac troponin I (cTnI) concentrations assayed with the Erenna
      Immunoassay System in Wistar rats (Crl:Wi[Han]) using the hydralazine model of
      cardiotoxicity. A single dose of hydralazine caused an increase of cTnI
      concentrations at six hours post-dose, followed by a sharp decrease at twenty
      four hours and a return to baseline at forty-eight hours. The second dose of
      hydralazine caused a smaller magnitude increase in cTnI concentrations at six
      hours as compared to the first dose. Also, cTnI concentrations returned to
      baseline at twenty-four hours after the second dose. The increased cTnI
      concentrations coincided with acute myocardial necrosis at histology. However,
      increased cTnI concentrations in the absence of microscopic lesions were
      identified in several rats. As cTnI concentrations decreased, microscopic changes
      in the heart matured to cardiomyophagy. In conclusion, the increases in cTnI
      concentrations six hours after the administration of hydralazine were indicative
      of a myocardial damage that did not consistently have a microscopic correlate.
      However, the window of increased cTnI concentrations was short, and only
      microscopic evaluation of the heart detected the damage at twenty-four to forty
      eight hours after the episode of acute myocardial necrosis.

PMID- 19854890
TI  - Identification and characterization of a small molecule antagonist of human
      VPAC(2) receptor.
AB  - The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate
      cyclase-activating peptide (PACAP) and their class II G protein-coupled receptors
      VPAC(1), VPAC(2), and PAC(1) play important roles in human physiology. No small
      molecule modulator has ever been reported for the VIP/PACAP receptors, and there
      is a lack of specific VPAC(2) antagonists. Via high-throughput screening of 1.67
      million compounds, we discovered a single small molecule antagonist of human
      VPAC(2), compound 1. Compound 1 inhibits VPAC(2)-mediated cAMP accumulation with
      an IC(50) of 3.8 microM and the ligand-activated beta-arrestin2 binding with an
      IC(50) of 2.3 microM. Compound 1 acts noncompetitively in Schild analysis. It is
      a specific VPAC(2) antagonist with no detectable agonist or antagonist activities
      on VPAC(1) or PAC(1). Compound 2, a close structural analog of compound 1, was
      also found to be weakly active. To our surprise, compound 1 is completely
      inactive on the closely related mouse VPAC(2). Chimera experiments indicate that
      compounds 1 and 2 bind to the seven transmembrane (7TM) region of the receptor as
      opposed to the N-terminal extracellular domain, where the natural ligand binds.
      Compound 1, being the first small molecular antagonist that is specific for
      VPAC(2), and the only VPAC(2) antagonist molecule known to date that
      allosterically interacts with the 7TM region, will be a valuable tool in further
      study of VPAC(2) and related receptors. This study also highlights the
      opportunities and challenges facing small molecule drug discovery for class II
      peptide G protein-coupled receptors.

PMID- 19854889
TI  - mu-Opioid receptor agonists differentially regulate the expression of miR-190 and
      NeuroD.
AB  - The agonists of mu-opioid receptor (OPRM1) induce extracellular signal-regulated
      kinase (ERK) phosphorylation through different pathways: morphine uses the
      protein kinase C (PKC)-pathway, whereas fentanyl functions in a beta-arrestin2
      dependent manner. In addition, the two pathways result in the different cellular
      location of phosphorylated ERK and the activation of different sets of
      transcriptional factors. In the current study, the influence of the two pathways
      on the expression of microRNAs (miRNAs) was investigated. After treating the
      primary culture of rat hippocampal neurons and the mouse hippocampi with morphine
      or fentanyl for 3 days, seven miRNAs regulated by one or two of the agonists were
      identified. One of the identified miRNAs, miR-190, was down-regulated by fentanyl
      but not by morphine. This down-regulation was attenuated by 1,4-diamino-2,3
      dicyano-1,4-bis(methylthio)butadiene (U0126), which blocks the phosphorylation of
      ERK. When fentanyl-induced but not morphine-induced ERK phosphorylation was
      blocked in the primary cultures from beta-arrestin2(-/-) mouse, fentanyl did not
      decrease the expression of miR-190. However, a PKC inhibitor that blocked
      morphine-induced ERK phosphorylation specifically had no effect on the miR-190
      down-regulation. Therefore the decrease in miR-190 expression resulted from the
      agonist-selective ERK phosphorylation. In addition, the expressional changes in
      one of the miR-190 targets, neurogenic differentiation 1 (NeuroD), correlated
      with those in miR-190 expression, suggesting the OPRM1 could regulate the NeuroD
      pathways via the control of miR-190 expression.

PMID- 19854891
TI  - Crystal structures of the lumazine protein from Photobacterium kishitanii in
      complexes with the authentic chromophore, 6,7-dimethyl- 8-(1'-D-ribityl)
      lumazine, and its analogues, riboflavin and flavin mononucleotide, at high
      resolution.
AB  - Lumazine protein (LumP) is a fluorescent accessory protein having 6,7-dimethyl-8
      (1'-d-ribityl) lumazine (DMRL) as its authentic chromophore. It modulates the
      emission of bacterial luciferase to shorter wavelengths with increasing luminous
      strength. To obtain structural information on the native structure as well as the
      interaction with bacterial luciferase, we have determined the crystal structures
      of LumP from Photobacterium kishitanii in complexes with DMRL and its analogues,
      riboflavin (RBF) and flavin mononucleotide (FMN), at resolutions of 2.00, 1.42,
      and 2.00 A. LumP consists of two beta barrels that have nearly identical folds,
      the N-terminal and C-terminal barrels. The structures of LumP in complex with all
      of the chromophores studied are all essentially identical, except around the
      chromophores. In all of the structures, the chromophore is tethered to the narrow
      cavity via many hydrogen bonds in the N-terminal domain. These are absent in the
      C-terminal domain. Hydrogen bonding in LumP-FMN is decreased in comparison with
      that in LumP-RBF because the phosphate moiety of FMN protrudes out of the narrow
      cavity. In LumP-DMRL, the side chain of Gln65 is close to the ring system, and a
      new water molecule that stabilizes the ligand is observed near Ser48. Therefore,
      DMRL packs more tightly in the ligand-binding site than RBF or FMN. A docking
      simulation of bacterial luciferase and LumP suggests that the chromophore is
      located close enough for direct energy transfer to occur. Moreover, the surface
      potentials around the ligand-binding sites of LumP and bacterial luciferase
      exhibit complementary charge distributions, which would have a significant effect
      on the interaction between LumP and luciferase.

PMID- 19854892
TI  - Global approaches for finding small RNA and small open reading frame functions.

PMID- 19854893
TI  - Cytoplasmic histidine kinase (HP0244)-regulated assembly of urease with UreI, a
      channel for urea and its metabolites, CO2, NH3, and NH4(+), is necessary for acid
      survival of Helicobacter pylori.
AB  - Helicobacter pylori colonizes the normal human stomach by maintaining both
      periplasmic and cytoplasmic pH close to neutral in the presence of gastric
      acidity. Urease activity, urea flux through the pH-gated urea channel, UreI, and
      periplasmic alpha-carbonic anhydrase are essential for colonization. Exposure to
      pH 4.5 for up to 180 min activates total bacterial urease threefold. Within 30
      min at pH 4.5, the urease structural subunits, UreA and UreB, and the Ni(2+)
      insertion protein, UreE, are recruited to UreI at the inner membrane. Formation
      of this complex and urease activation depend on expression of the cytoplasmic
      sensor histidine kinase, HP0244. Its deletion abolishes urease activation and
      assembly, impairs cytoplasmic and periplasmic pH homeostasis, and depolarizes the
      cells, with an approximately 7-log loss of survival at pH 2.5, even in 10 mM
      urea. Associated with this assembly, UreI is able to transport NH(3), NH(4)(+),
      and CO(2), as shown by changes in cytoplasmic pH following exposure to NH(4)Cl or
      CO(2). To be able to colonize cells in the presence of the highly variable pH of
      the stomach, the organism expresses two pH-sensor histidine kinases, one, HP0165,
      responding to a moderate fall in periplasmic pH and the other, HP0244, responding
      to cytoplasmic acidification at a more acidic medium pH. Assembly of a pH
      regulatory complex of active urease with UreI provides an advantage for
      periplasmic buffering.

PMID- 19854894
TI  - Accumulation of intermediates of the carbon-phosphorus lyase pathway for
      phosphonate degradation in phn mutants of Escherichia coli.
AB  - The catabolism of phosphonic acids occurs in Escherichia coli by the carbon
      phosphorus lyase pathway, which is governed by the 14-cistron phn operon. Here,
      several compounds are shown to accumulate in strains of E. coli with genetic
      blocks in various phn cistrons when the strains are fed with phosphonate.

PMID- 19854895
TI  - FtsN--trigger for septation.

PMID- 19854896
TI  - Control of thioredoxin reductase gene (trxB) transcription by SarA in
      Staphylococcus aureus.
AB  - Thioredoxin reductase (encoded by trxB) protects Staphylococcus aureus against
      oxygen or disulfide stress and is indispensable for growth. Among the different
      sarA family mutants analyzed, transcription of trxB was markedly elevated in the
      sarA mutant under conditions of aerobic as well as microaerophilic growth,
      indicating that SarA acts as a negative regulator of trxB expression. Gel shift
      analysis showed that purified SarA protein binds directly to the trxB promoter
      region DNA in vitro. DNA binding of SarA was essential for repression of trxB
      transcription in vivo in S. aureus. Northern blot analysis and DNA binding
      studies of the purified wild-type SarA and the mutant SarAC9G with oxidizing
      agents indicated that oxidation of Cys-9 reduced the binding of SarA to the trxB
      promoter DNA. Oxidizing agents, in particular diamide, could further enhance
      transcription of the trxB gene in the sarA mutant, suggesting the presence of a
      SarA-independent mode of trxB induction. Analysis of two oxidative stress
      responsive sarA regulatory target genes, trxB and sodM, with various mutant sarA
      constructs showed a differential ability of the SarA to regulate expression of
      the two above-mentioned genes in vivo. The overall data demonstrate the important
      role played by SarA in modulating expression of genes involved in oxidative
      stress resistance in S. aureus.

PMID- 19854897
TI  - Functional characterization of Lpt3 and Lpt6, the inner-core lipooligosaccharide
      phosphoethanolamine transferases from Neisseria meningitidis.
AB  - The lipooligosaccharide (LOS) of Neisseria meningitidis contains heptose (Hep)
      residues that are modified with phosphoethanolamine (PEtn) at the 3 (3-PEtn)
      and/or 6 (6-PEtn) position. The lpt3 (NMB2010) and lpt6 (NMA0408) genes of N.
      meningitidis, which are proposed to encode the required HepII 3- and 6-PEtn
      transferases, respectively, were cloned and overexpressed as C-terminally
      polyhistidine-tagged fusion proteins in Escherichia coli and found to localize to
      the inner membrane, based on sucrose density gradient centrifugation. Lpt3-His(6)
      and Lpt6-His(6) were purified from Triton X-100-solubilized membranes by nickel
      chelation chromatography, and dot blot analysis of enzymatic reactions with 3
      PEtn- and 6-PEtn-specific monoclonal antibodies demonstrated conclusively that
      Lpt3 and Lpt6 are phosphatidylethanolamine-dependent LOS HepII 3- and 6-PEtn
      transferases, respectively, and that both enzymes are capable of transferring
      PEtn to both fully acylated LOS and de-O-acylated (de-O-Ac) LOS. Further
      enzymatic studies using capillary electrophoresis-mass spectrometry (MS)
      demonstrated that both Lpt3 and Lpt6 are capable of transferring PEtn to de-O-Ac
      LOS molecules already containing PEtn at the 6 and 3 positions of HepII,
      respectively, demonstrating that there is no obligate order of PEtn addition in
      the generation of 3,6-di-PEtn LOS moieties in vitro.

PMID- 19854898
TI  - Combined genomic and proteomic approaches identify gene clusters involved in
      anaerobic 2-methylnaphthalene degradation in the sulfate-reducing enrichment
      culture N47.
AB  - The highly enriched deltaproteobacterial culture N47 anaerobically oxidizes the
      polycyclic aromatic hydrocarbons naphthalene and 2-methylnaphthalene, with
      sulfate as the electron acceptor. Combined genome sequencing and liquid
      chromatography-tandem mass spectrometry-based shotgun proteome analyses were
      performed to identify genes and proteins involved in anaerobic aromatic
      catabolism. Proteome analysis of 2-methylnaphthalene-grown N47 cells resulted in
      the identification of putative enzymes catalyzing the anaerobic conversion of 2
      methylnaphthalene to 2-naphthoyl coenzyme A (2-naphthoyl-CoA), as well as the
      reductive ring cleavage of 2-naphthoyl-CoA, leading to the formation of acetyl
      CoA and CO(2). The glycyl radical-catalyzed fumarate addition to the methyl group
      of 2-methylnaphthalene is catalyzed by naphthyl-2-methyl-succinate synthase
      (Nms), composed of alpha-, beta-, and gamma-subunits that are encoded by the
      genes nmsABC. Located upstream of nmsABC is nmsD, encoding the Nms-activating
      enzyme, which harbors the characteristic [Fe(4)S(4)] cluster sequence motifs of S
      adenosylmethionine radical enzymes. The bns gene cluster, coding for enzymes
      involved in beta-oxidation reactions converting naphthyl-2-methyl-succinate to 2
      naphthoyl-CoA, was found four intervening open reading frames further downstream.
      This cluster consists of eight genes (bnsABCDEFGH) corresponding to 8.1 kb, which
      are closely related to genes for enzymes involved in anaerobic toluene
      degradation within the denitrifiers "Aromatoleum aromaticum" EbN1, Azoarcus sp.
      strain T, and Thauera aromatica. Another contiguous DNA sequence harbors the gene
      for 2-naphthoyl-CoA reductase (ncr) and 16 additional genes that were found to be
      expressed in 2-methylnaphthalene-grown cells. These genes code for enzymes that
      were supposed to catalyze the dearomatization and ring cleavage reactions
      converting 2-naphthoyl-CoA to acetyl-CoA and CO(2). Comparative sequence analysis
      of the four encoding subunits (ncrABCD) showed the gene product to have the
      closest similarity to the Azoarcus type of benzoyl-CoA reductase. The present
      work provides the first insight into the genetic basis of anaerobic 2
      methylnaphthalene metabolism and delivers implications for understanding
      contaminant degradation.

PMID- 19854899
TI  - Response of the oxygen sensor NreB to air in vivo: Fe-S-containing NreB and apo
      NreB in aerobically and anaerobically growing Staphylococcus carnosus.
AB  - The sensor kinase NreB from Staphylococcus carnosus contains an O(2)-sensitive
      [4Fe-4S](2+) cluster which is converted by O(2) to a [2Fe-2S](2+) cluster,
      followed by complete degradation and formation of Fe-S-less apo-NreB. NreB.[2Fe
      2S](2+) and apoNreB are devoid of kinase activity. NreB contains four Cys
      residues which ligate the Fe-S clusters. The accessibility of the Cys residues to
      alkylating agents was tested and used to differentiate Fe-S-containing and Fe-S
      less NreB. In a two-step labeling procedure, accessible Cys residues in the
      native protein were first labeled by iodoacetate. In the second step, Cys
      residues not labeled in the first step were alkylated with the fluorescent
      monobromobimane (mBBr) after denaturing of the protein. In purified (aerobic)
      apoNreB, most (96%) of the Cys residues were alkylated in the first step, but in
      anaerobic (Fe-S-containing) NreB only a small portion (23%) were alkylated. In
      anaerobic bacteria, a very small portion of the Cys residues of NreB (9%) were
      accessible to alkylation in the native state, whereas most (89%) of the Cys
      residues from aerobic bacteria were accessible. The change in accessibility
      allowed determination of the half-time (6 min) for the conversion of NreB x [4Fe
      4S](2+) to apoNreB after the addition of air in vitro. Overall, in anaerobic
      bacteria most of the NreB exists as NreB x [4Fe-4S](2+), whereas in aerobic
      bacteria the (Fe-S-less) apoNreB is predominant and represents the physiological
      form. The number of accessible Cys residues was also determined by iodoacetate
      alkylation followed by mass spectrometry of Cys-containing peptides. The pattern
      of mass increases confirmed the results from the two-step labeling experiments.

PMID- 19854900
TI  - Three-dimensional structure of different functional forms of the Vibrio cholerae
      hemolysin oligomer: a cryo-electron microscopic study.
AB  - Vibrio cholerae hemolysin (HlyA) is a 65-kDa water-soluble pore-forming toxin
      that causes lysis of eukaryotic cells by destroying selective permeability of the
      plasma membrane bilayer. The HlyA monomer self-assembles on the target cell
      surface to the more stable beta-barrel amphipathic heptamer, which inserts into
      the membrane bilayer to form a diffusion channel. Deletion of the 15-kDa beta
      prism lectin domain at the C terminus generates a 50-kDa hemolysin variant
      (HlyA50) with an approximately 1,000-fold decrease in hemolytic activity. Because
      functional differences are eventually dictated by structural differences, we
      determined three-dimensional structures of 65- and 50-kDa HlyA oligomers, using
      cryo-electron microscopy and single-particle methods. Our study clearly shows
      that the HlyA oligomer has sevenfold symmetry but that the HlyA50 oligomer is an
      asymmetric molecule. The HlyA oligomer has bowl-like, arm-like, and ring-like
      domains. The bowl-like domain is coupled with the ring-like domain, and seven
      side openings are present just beneath the ring-like domain. Although a central
      channel is present in both HlyA and HlyA50 oligomers, they differ in pore size as
      well as in shape of the molecules and channel. These structural differences may
      be relevant to the striking difference in efficiencies of functional channel
      formation by the two toxin forms.

PMID- 19854901
TI  - Structure and regulation of the gab gene cluster, involved in the gamma
      aminobutyric acid shunt, are controlled by a sigma54 factor in Bacillus
      thuringiensis.
AB  - The structure and regulation of the gab gene cluster, involved in gamma
      aminobutyric acid (GABA) shunt, were studied by characterizing gabT and gabD
      genes cloned from Bacillus thuringiensis. Deletions of the gabT and gabD genes in
      B. thuringiensis strain HD-73 did not affect the growth of mutant strains in rich
      culture media, but the growth of a gabT deletion mutant strain was reduced in
      basic media (containing 0.2% GABA). Genome analysis indicates that the structure
      of the gab gene cluster in B. thuringiensis HD-73 is different from that in
      Escherichia coli and Bacillus subtilis but is common in strains of the Bacillus
      cereus group. This suggests that the gene cluster involved in GABA shunt is
      specific to the B. cereus group. Based on reverse transcription-PCR and
      transcriptional fusion analysis, we confirmed that the gabT and gabD genes belong
      to different transcriptional units, while the gabD and gabR genes form an operon.
      We also demonstrated that the gabR gene plays a positive regulatory role in gabD
      and gabT expression. The GabR protein may be a sigma(54)-dependent
      transcriptional activator, according to a conserved domain search in the NCBI
      database, and it is highly conserved in the B. cereus group. The -24/-12
      consensus sequence of a promoter upstream from gabT suggests that the promoter
      can be recognized by a sigma(54) factor. Further analysis of the genetic
      complementation studies also suggests that the expression of the gabT gene is
      controlled by a sigma(54) factor. Thus, the expression of the gab cluster is
      regulated by a sigma(54) factor by way of the transcription activator GabR.

PMID- 19854903
TI  - The AraC/XylS family activator RhaS negatively autoregulates rhaSR expression by
      preventing cyclic AMP receptor protein activation.
AB  - The Escherichia coli RhaR protein activates expression of the rhaSR operon in the
      presence of its effector, L-rhamnose. The resulting RhaS protein (plus L
      rhamnose) activates expression of the L-rhamnose catabolic and transport operons,
      rhaBAD and rhaT, respectively. Here, we further investigated our previous finding
      that rhaS deletion resulted in a threefold increase in rhaSR promoter activity,
      suggesting RhaS negative autoregulation of rhaSR. We found that RhaS
      autoregulation required the cyclic AMP receptor protein (CRP) binding site at
      rhaSR and that RhaS was able to bind to the RhaR binding site at rhaSR. In
      contrast to the expected repression, we found that in the absence of both RhaR
      and the CRP binding site at the rhaSR promoter, RhaS activated expression to a
      level comparable with RhaR activation of the same promoter. However, when the
      promoter included the RhaR and CRP binding sites, the level of activation by RhaS
      and CRP was much lower than that by RhaR and CRP, suggesting that CRP could not
      fully coactivate with RhaS. Taken together, our results indicate that RhaS
      negative autoregulation involves RhaS competition with RhaR for binding to the
      RhaR binding site at rhaSR. Although RhaS and RhaR activate rhaSR transcription
      to similar levels, CRP cannot effectively coactivate with RhaS. Therefore, once
      RhaS reaches a relatively high protein concentration, presumably sufficient to
      saturate the RhaS-activated promoters, there will be a decrease in rhaSR
      transcription. We propose a model in which differential DNA bending by RhaS and
      RhaR may be the basis for the difference in CRP coactivation.

PMID- 19854902
TI  - Transcriptional and functional analysis of the Neisseria gonorrhoeae Fur regulon.
AB  - To ensure survival in the host, bacteria have evolved strategies to acquire the
      essential element iron. In Neisseria gonorrhoeae, the ferric uptake regulator Fur
      regulates metabolism through transcriptional control of iron-responsive genes by
      binding conserved Fur box (FB) sequences in promoters during iron-replete growth.
      Our previous studies showed that Fur also controls the transcription of secondary
      regulators that may, in turn, control pathways important to pathogenesis,
      indicating an indirect role for Fur in controlling these downstream genes. To
      better define the iron-regulated cascade of transcriptional control, we combined
      three global strategies--temporal transcriptome analysis, genomewide in silico FB
      prediction, and Fur titration assays (FURTA)--to detect genomic regions able to
      bind Fur in vivo. The majority of the 300 iron-repressed genes were predicted to
      be of unknown function, followed by genes involved in iron metabolism, cell
      communication, and intermediary metabolism. The 107 iron-induced genes encoded
      hypothetical proteins or energy metabolism functions. We found 28 predicted FBs
      in FURTA-positive clones in the promoters and within the open reading frames of
      iron-repressed genes. We found lower levels of conservation at critical thymidine
      residues involved in Fur binding in the FB sequence logos of FURTA-positive
      clones with intragenic FBs than in the sequence logos generated from FURTA
      positive promoter regions. In electrophoretic mobility shift assay studies,
      intragenic FBs bound Fur with a lower affinity than intergenic FBs. Our findings
      further indicate that transcription under iron stress is indirectly controlled by
      Fur through 12 potential secondary regulators.

PMID- 19854904
TI  - The siderophore pyoverdine of Pseudomonas syringae pv. tabaci 6605 is an
      intrinsic virulence factor in host tobacco infection.
AB  - To investigate the role of iron uptake mediated by the siderophore pyoverdine in
      the virulence of the plant pathogen Pseudomonas syringae pv. tabaci 6605, three
      predicted pyoverdine synthesis-related genes, pvdJ, pvdL, and fpvA, were mutated.
      The pvdJ, pvdL, and fpvA genes encode the pyoverdine side chain peptide
      synthetase III L-Thr-L-Ser component, the pyoverdine chromophore synthetase, and
      the TonB-dependent ferripyoverdine receptor, respectively. The Delta pvdJ and
      Delta pvdL mutants were unable to produce pyoverdine in mineral salts-glucose
      medium, which was used for the iron-depleted condition. Furthermore, the Delta
      pvdJ and Delta pvdL mutants showed lower abilities to produce tabtoxin,
      extracellular polysaccharide, and acyl homoserine lactones (AHLs), which are
      quorum-sensing molecules, and consequently had reduced virulence on host tobacco
      plants. In contrast, all of the mutants had accelerated swarming ability and
      increased biosurfactant production, suggesting that swarming motility and
      biosurfactant production might be negatively controlled by pyoverdine. Scanning
      electron micrographs of the surfaces of tobacco leaves inoculated with the mutant
      strains revealed only small amounts of extracellular polymeric matrix around
      these mutants, indicating disruption of the mature biofilm. Tolerance to
      antibiotics was drastically increased for the Delta pvdL mutant, as for the Delta
      psyI mutant, which is defective in AHL production. These results demonstrated
      that pyoverdine synthesis and the quorum-sensing system of Pseudomonas syringae
      pv. tabaci 6605 are indispensable for virulence in host tobacco infection and
      that AHL may negatively regulate tolerance to antibiotics.

PMID- 19854905
TI  - Conservation of structure and protein-protein interactions mediated by the
      secreted mycobacterial proteins EsxA, EsxB, and EspA.
AB  - Mycobacterium tuberculosis EsxA and EsxB proteins are founding members of the
      WXG100 (WXG) protein family, characterized by their small size (approximately 100
      amino acids) and conserved WXG amino acid motif. M. tuberculosis contains 11
      tandem pairs of WXG genes; each gene pair is thought to be coexpressed to form a
      heterodimer. The precise role of these proteins in the biology of M. tuberculosis
      is unknown, but several of the heterodimers are secreted, which is important for
      virulence. However, WXG proteins are not simply virulence factors, since
      nonpathogenic mycobacteria also express and secrete these proteins. Here we show
      that three WXG heterodimers have structures and properties similar to those of
      the M. tuberculosis EsxBA (MtbEsxBA) heterodimer, regardless of their host
      species and apparent biological function. Biophysical studies indicate that the
      WXG proteins from M. tuberculosis (EsxG and EsxH), Mycobacterium smegmatis (EsxA
      and EsxB), and Corynebacterium diphtheriae (EsxA and EsxB) are heterodimers and
      fold into a predominately alpha-helical structure. An in vivo protein-protein
      interaction assay was modified to identify proteins that interact specifically
      with the native WXG100 heterodimer. MtbEsxA and MtbEsxB were fused into a single
      polypeptide, MtbEsxBA, to create a biomimetic bait for the native heterodimer.
      The MtbEsxBA bait showed specific association with several esx-1-encoded proteins
      and EspA, a virulence protein secreted by ESX-1. The MtbEsxBA fusion peptide was
      also utilized to identify residues in both EsxA and EsxB that are important for
      establishing protein interactions with Rv3871 and EspA. Together, the results are
      consistent with a model in which WXG proteins perform similar biological roles in
      virulent and nonvirulent species.

PMID- 19854907
TI  - Conjugative transfer of the integrative and conjugative element ICEBs1 from
      Bacillus subtilis likely initiates at the donor cell pole.

PMID- 19854906
TI  - Molecular basis for the role of Staphylococcus aureus penicillin binding protein
      4 in antimicrobial resistance.
AB  - Penicillin binding proteins (PBPs) are membrane-associated proteins that catalyze
      the final step of murein biosynthesis. These proteins function as either
      transpeptidases or carboxypeptidases and in a few cases demonstrate
      transglycosylase activity. Both transpeptidase and carboxypeptidase activities of
      PBPs occur at the D-Ala-D-Ala terminus of a murein precursor containing a
      disaccharide pentapeptide comprising N-acetylglucosamine and N-acetyl-muramic
      acid-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala. Beta-lactam antibiotics inhibit these enzymes
      by competing with the pentapeptide precursor for binding to the active site of
      the enzyme. Here we describe the crystal structure, biochemical characteristics,
      and expression profile of PBP4, a low-molecular-mass PBP from Staphylococcus
      aureus strain COL. The crystal structures of PBP4-antibiotic complexes reported
      here were determined by molecular replacement, using the atomic coordinates
      deposited by the New York Structural Genomics Consortium. While the pbp4 gene is
      not essential for the viability of S. aureus, the knockout phenotype of this gene
      is characterized by a marked reduction in cross-linked muropeptide and increased
      vancomycin resistance. Unlike other PBPs, we note that expression of PBP4 was not
      substantially altered under different experimental conditions, nor did it change
      across representative hospital- or community-associated strains of S. aureus that
      were examined. In vitro data on purified recombinant S. aureus PBP4 suggest that
      it is a beta-lactamase and is not trapped as an acyl intermediate with beta
      lactam antibiotics. Put together, the expression analysis and biochemical
      features of PBP4 provide a framework for understanding the function of this
      protein in S. aureus and its role in antimicrobial resistance.

PMID- 19854908
TI  - Appendage-mediated surface adherence of Sulfolobus solfataricus.
AB  - Attachment of microorganisms to surfaces is a prerequisite for colonization and
      biofilm formation. The hyperthermophilic crenarchaeote Sulfolobus solfataricus
      was able to attach to a variety of surfaces, such as glass, mica, pyrite, and
      carbon-coated gold grids. Deletion mutant analysis showed that for initial
      attachment the presence of flagella and pili is essential. Attached cells
      produced extracellular polysaccharides containing mannose, galactose, and N
      acetylglucosamine. Genes possibly involved in the production of the extracellular
      polysaccharides were identified.

PMID- 19854909
TI  - Mismatch correction modulates mutation frequency and pilus phase and antigenic
      variation in Neisseria gonorrhoeae.
AB  - The mismatch correction (MMC) system repairs DNA mismatches and single nucleotide
      insertions or deletions postreplication. To test the functions of MMC in the
      obligate human pathogen Neisseria gonorrhoeae, homologues of the core MMC genes
      mutS and mutL were inactivated in strain FA1090. No mutH homologue was found in
      the FA1090 genome, suggesting that gonococcal MMC is not methyl directed. MMC
      mutants were compared to a mutant in uvrD, the helicase that functions with MMC
      in Escherichia coli. Inactivation of MMC or uvrD increased spontaneous resistance
      to rifampin and nalidixic acid, and MMC/uvrD double mutants exhibited higher
      mutation frequencies than any single mutant. Loss of MMC marginally enhanced the
      transformation efficiency of DNA carrying a single nucleotide mismatch but not
      that of DNA with a 1-kb insertion. Unlike the exquisite UV sensitivity of the
      uvrD mutant, inactivating MMC did not affect survival after UV irradiation. MMC
      and uvrD mutants exhibited increased PilC-dependent pilus phase variation. mutS
      deficient gonococci underwent an increased frequency of pilin antigenic
      variation, whereas uvrD had no effect. Recombination tracts in the mutS pilin
      variants were longer than in parental gonococci but utilized the same donor pilS
      loci. These results show that gonococcal MMC repairs mismatches and small
      insertion/deletions in DNA and also affects the recombination events underlying
      pilin antigenic variation. The differential effects of MMC and uvrD in gonococci
      unexpectedly reveal that MMC can function independently of uvrD in this human
      specific pathogen.

PMID- 19854910
TI  - Identification and characterization of noncoding small RNAs in Streptococcus
      pneumoniae serotype 2 strain D39.
AB  - We report a search for small RNAs (sRNAs) in the low-GC, gram-positive human
      pathogen Streptococcus pneumoniae. Based on bioinformatic analyses by Livny et
      al. (J. Livny, A. Brencic, S. Lory, and M. K. Waldor, Nucleic Acids Res. 34:3484
      3493, 2006), we tested 40 candidates by Northern blotting and confirmed the
      expression of nine new and one previously reported (CcnA) sRNAs in strain D39.
      CcnA is one of five redundant sRNAs reported by Halfmann et al. (A. Halfmann, M.
      Kovacs, R. Hakenbeck, and R. Bruckner, Mol. Microbiol. 66:110-126, 2007) that are
      positively controlled by the CiaR response regulator. We characterized 3 of these
      14 sRNAs: Spd-sr17 (144 nucleotides [nt]; decreased in stationary phase), Spd
      sr37 (80 nt; strongly expressed in all growth phases), and CcnA (93 nt; induced
      by competence stimulatory peptide). Spd-sr17 and CcnA likely fold into structures
      containing single-stranded regions between hairpin structures, whereas Spd-sr37
      forms a base-paired structure. Primer extension mapping and ectopic expression in
      deletion/insertion mutants confirmed the independent expression of the three
      sRNAs. Microarray analyses indicated that insertion/deletion mutants in spd-sr37
      and ccnA exerted strong cis-acting effects on the transcription of adjacent
      genes, indicating that these sRNA regions are also cotranscribed in operons.
      Deletion or overexpression of the three sRNAs did not cause changes in growth,
      certain stress responses, global transcription, or virulence. Constitutive
      ectopic expression of CcnA reversed some phenotypes of D39 Delta ciaR mutants,
      but attempts to link CcnA to -E to comC as a target were inconclusive in ciaR(+)
      strains. These results show that S. pneumoniae, which lacks known RNA chaperones,
      expresses numerous sRNAs, but three of these sRNAs do not strongly affect common
      phenotypes or transcription patterns.

PMID- 19854911
TI  - Metabolic control of virulence genes in Brucella abortus: HutC coordinates virB
      expression and the histidine utilization pathway by direct binding to both
      promoters.
AB  - Type IV secretion systems (T4SS) are multicomponent machineries involved in the
      translocation of effector molecules across the bacterial cell envelope. The virB
      operon of Brucella abortus codes for a T4SS that is essential for virulence and
      intracellular multiplication of the bacterium in the host. Previous studies
      showed that the virB operon of B. abortus is tightly regulated within the host
      cells. In order to identify factors implicated in the control of virB expression,
      we searched for proteins of Brucella that directly bind to the virB promoter
      (P(virB)). Using different procedures, we isolated a 27-kDa protein that binds
      specifically to P(virB). This protein was identified as HutC, the transcriptional
      repressor of the histidine utilization (hut) genes. Analyses of virB and hut
      promoter activity revealed that HutC exerts two different roles: it acts as a
      coactivator of transcription of the virB operon, whereas it represses the hut
      genes. Such activities were observed both intracellularly and in bacteria
      incubated under conditions that resemble the intracellular environment.
      Electrophoresis mobility shift assays (EMSA) and DNase I footprinting experiments
      revealed the structure, affinity, and localization of the HutC-binding sites and
      supported the regulatory role of HutC in both hut and virB promoters. Taken
      together, these results indicate that Brucella coopted the function of HutC to
      coordinate the Hut pathway with transcriptional regulation of the virB genes,
      probably as a way to sense its own metabolic state and develop adaptive responses
      to overcome intracellular host defenses.

PMID- 19854912
TI  - Complete genome sequence of Anaplasma marginale subsp. centrale.
AB  - Anaplasma marginale subsp. centrale is a naturally attenuated subtype that has
      been used as a vaccine for a century. We sequenced the genome of this organism
      and compared it to those of virulent senso stricto A. marginale strains. The
      comparison markedly narrows the number of outer membrane protein candidates for
      development of a safer inactivated vaccine and provides insight into the
      diversity among strains of senso lato A. marginale.

PMID- 19854913
TI  - Pantothenate kinase from the thermoacidophilic archaeon Picrophilus torridus.
AB  - Pantothenate kinase (CoaA) catalyzes the first step of the coenzyme A (CoA)
      biosynthetic pathway and controls the intracellular concentrations of CoA through
      feedback inhibition in bacteria. An alternative enzyme found in archaea, pantoate
      kinase, is missing in the order Thermoplasmatales. The PTO0232 gene from
      Picrophilus torridus, a thermoacidophilic euryarchaeon, is shown to be a distant
      homologue of the prokaryotic type I CoaA. The cloned gene clearly complements the
      poor growth of the temperature-sensitive Escherichia coli CoaA mutant strain ts9,
      and the recombinant protein expressed in E. coli cells transfers phosphate to
      pantothenate at pH 5 and 55 degrees C. In contrast to E. coli CoaA, the P.
      torridus enzyme is refractory to feedback regulation by CoA, indicating that in
      P. torridus cells the CoA levels are not regulated by the CoaA step. These data
      suggest the existence of two subtypes within the class of prokaryotic type I
      CoaAs.

PMID- 19854915
TI  - Vegetation and soil environment influence the spatial distribution of root
      associated fungi in a mature beech-maple forest.
AB  - Although the level of diversity of root-associated fungi can be quite high, the
      effect of plant distribution and soil environment on root-associated fungal
      communities at fine spatial scales has received little attention. Here, we
      examine how soil environment and plant distribution affect the occurrence,
      diversity, and community structure of root-associated fungi at local patch scales
      within a mature forest. We used terminal restriction fragment length polymorphism
      and sequence analysis to detect 63 fungal species representing 28 different
      genera colonizing tree root tips. At least 32 species matched previously
      identified mycorrhizal fungi, with the remaining fungi including both
      saprotrophic and parasitic species. Root fungal communities were significantly
      different between June and September, suggesting a rapid temporal change in root
      fungal communities. Plant distribution affected root fungal communities, with
      some root fungi positively correlated with tree diameter and herbaceous-plant
      coverage. Some aspects of the soil environment were correlated with root fungal
      community structure, with the abundance of some root fungi positively correlated
      with soil pH and moisture content in June and with soil phosphorous (P) in
      September. Fungal distribution and community structure may be governed by plant
      soil interactions at fine spatial scales within a mature forest. Soil P may play
      a role in structuring root fungal communities at certain times of the year.

PMID- 19854916
TI  - Presence and prevalence of viruses in local and migratory honeybees (Apis
      mellifera) in Massachusetts.
AB  - Migratory and local bees in Massachusetts were analyzed for seven viruses. Three
      were detected: black queen cell virus (BQCV), deformed wing virus (DWV), and
      sacbrood virus (SBV). DWV was most common, followed closely by BQCV and then by
      SBV. BQCV and SBV were present at significantly higher rates in the migratory
      bees assayed, bringing into question the impact that these bees have on the
      health of local bee populations.

PMID- 19854914
TI  - Investigation of food and environmental exposures relating to the epidemiology of
      Campylobacter coli in humans in Northwest England.
AB  - This study uses multilocus sequence typing (MLST) to investigate the epidemiology
      of Campylobacter coli in a continuous study of a population in Northwest England.
      All cases of Campylobacter identified in four Local Authorities (government
      administrative boundaries) between 2003 and 2006 were identified to species level
      and then typed, using MLST. Epidemiological information was collected for each of
      these cases, including food and recreational exposure variables, and the
      epidemiologies of C. jejuni and C. coli were compared using case-case
      methodology. Samples of surface water thought to represent possible points of
      exposure to the populations under study were also sampled, and campylobacters
      were typed with multilocus sequence typing. Patients with C. coli were more
      likely to be older and female than patients with C. jejuni. In logistic
      regression, C. coli infection was positively associated with patients eating
      undercooked eggs, eating out, and reporting problems with their water supply
      prior to illness. C. coli was less associated with consuming pork products. Most
      of the cases of C. coli yielded sequence types described elsewhere in both
      livestock and poultry, but several new sequence types were also identified in
      human cases and water samples. There was no overlap between types identified in
      humans and surface waters, and genetic analysis suggested three distinct clades
      but with several "intermediate" types from water that were convergent with the
      human clade. There is little evidence to suggest that epidemiological differences
      between human cases of C. coli and C. jejuni are a result of different food or
      behavioral exposures alone.

PMID- 19854917
TI  - Genome shuffling in Clostridium diolis DSM 15410 for improved 1,3-propanediol
      production.
AB  - Several microorganisms are known for their efficient anaerobic conversion of
      glycerol to 1,3-propanediol, with Clostridium diolis DSM 15410 as one of the
      better performers in terms of molar yield and volumetric productivity. However,
      this performance is still insufficient to compete with established chemical
      processes. Previous studies have shown that high concentrations of 1,3
      propanediol, glycerol, and fermentation side products can limit the productivity
      of C. diolis DSM 15410. Here, we describe the use of genome shuffling for
      improved 1,3-propanediol fermentation by the strict anaerobe C. diolis DSM 15410.
      By using chemical mutagenesis, strains with superior substrate and product
      tolerance levels were isolated and higher product yields were obtained. These
      superior strains were then used for genome shuffling and selection for 1,3
      propanediol and organic acid tolerance. After four rounds of genome shuffling and
      selection, significant improvements were observed, with one strain attaining a
      1,3-propanediol volumetric yield of 85 g/liter. This result represents an 80%
      improvement compared to the yield from the parental wild-type strain.

PMID- 19854918
TI  - Resistance of Saccharomyces cerevisiae to high concentrations of furfural is
      based on NADPH-dependent reduction by at least two oxireductases.
AB  - Biofuels derived from lignocellulosic biomass hold promises for a sustainable
      fuel economy, but several problems hamper their economical feasibility. One
      important problem is the presence of toxic compounds in processed lignocellulosic
      hydrolysates, with furfural as a key toxin. While Saccharomyces cerevisiae has
      some intrinsic ability to reduce furfural to the less-toxic furfuryl alcohol,
      higher resistance is necessary for process conditions. By comparing an evolved,
      furfural-resistant strain and its parent in microaerobic, glucose-limited
      chemostats at increasing furfural challenge, we elucidate key mechanism and the
      molecular basis of both natural and high-level furfural resistance. At lower
      concentrations of furfural, NADH-dependent oxireductases are the main defense
      mechanism. At furfural concentrations above 15 mM, however, (13)C-flux and global
      array-based transcript analysis demonstrated that the NADPH-generating flux
      through the pentose phosphate pathway increases and that NADPH-dependent
      oxireductases become the major resistance mechanism. The transcript analysis
      further revealed that iron transmembrane transport is upregulated in response to
      furfural. While these responses occur in both strains, high-level resistance in
      the evolved strain was based on strong induction of ADH7, the uncharacterized
      open reading frame (ORF) YKL071W, and four further, likely NADPH-dependent,
      oxireductases. By overexpressing the ADH7 gene and the ORF YKL071W, we inversely
      engineered significantly increased furfural resistance in the parent strain,
      thereby demonstrating that these two enzymes are key elements of the resistance
      phenotype.

PMID- 19854919
TI  - Enteric viruses in raw vegetables and groundwater used for irrigation in South
      Korea.
AB  - Raw vegetables irrigated with groundwater that may contain enteric viruses can be
      associated with food-borne viral disease outbreaks. In this study, we performed
      reverse transcription-PCR (RT-PCR) and cell culture-PCR to monitor the occurrence
      of enteric viruses in groundwater samples and in raw vegetables that were
      cultivated using that groundwater in South Korea. Samples were collected 10 times
      from three farms located in Gyeonggi Province, South Korea. RT-PCR and cell
      culture-PCR were performed to detect adenoviruses (AdVs), enteroviruses (EVs),
      noroviruses (NoVs), and rotaviruses, followed by sequence analyses of the
      detected strains. Of the 29 groundwater samples and the 30 vegetable samples,
      five (17%) and three (10%) were positive for enteric viruses, respectively. AdVs
      were the most frequently detected viruses in four groundwater and three vegetable
      samples. EVs and NoVs were detected in only one groundwater sample and one
      spinach sample, respectively. The occurrence of enteric viruses in groundwater
      and vegetable samples was not correlated with the water temperature and the
      levels of indicator bacteria, respectively. Phylogenetic analysis indicated that
      most of the detected AdVs were temporally distributed, irrespective of sample
      type. Our results indicate that raw vegetables may be contaminated with a broad
      range of enteric viruses, which may originate from virus-infected farmers and
      virus-contaminated irrigation water, and these vegetables may act as a potential
      vector of food-borne viral transmission.

PMID- 19854920
TI  - Nonfermentative thermoalkaliphilic growth is restricted to alkaline environments.
AB  - Caldalkalibacillus thermarum strain TA2.A1 grew in pH-controlled batch culture
      containing a fermentable growth substrate (i.e., sucrose) from pH 7.5 to 10.0
      with no significant change in the specific growth rate, suggesting that this
      bacterium was a facultative alkaliphile. However, when strain TA2.A1 was grown on
      a nonfermentable carbon source, such as succinate or malate, no growth was
      observed until the external pH was >9.0, suggesting that this bacterium was an
      obligate alkaliphile. Succinate transport and sucrose transport by strain TA2.A1
      showed pH profiles similar to that of growth on these carbon sources, and the
      molar growth yield on sucrose was higher at pH 9.5 than at pH 7.5, despite the
      increased energy demands on the cell for intracellular pH regulation. Succinate
      transport, succinate-dependent oxygen consumption, and succinate dehydrogenase
      and F(1)F(o)-ATPase specific activities were all significantly lower in cultures
      of strain TA2.A1 grown at pH 7.5 than in those cultured at pH 9.5. No significant
      ATP synthesis via the F(1)F(o)-ATP synthase was detected until the external pH
      was >8.5. On the basis of these results, we propose that nonfermentative
      thermoalkaliphilic growth is specialized to function at high pH values, but not
      at pH values near neutral pH.

PMID- 19854921
TI  - Influence of species specificity and other factors on bacteria associated with
      the coral Stylophora pistillata in Taiwan.
AB  - Species of bacteria associated with Stylophora pistillata were determined by
      analyses of 16S ribosomal genes. Coral samples were taken from two distinct sites
      at Kenting, in the far south of Taiwan; three coral colonies at each site were
      tagged and sampled in the winter and summer of 2007. Six hundred 16S rRNA gene
      clones were selected and sequenced for diversity analysis and community
      comparison. LIBSHUFF and nonparametric multiple dimensional scaling analyses
      showed variations in the composition of the coral-associated bacteria in the
      different samples, suggesting that seasonal and geographic factors and variations
      in individual coral colonies were all vital drivers of the structure of the S.
      pistillata-associated bacterial community. To examine the association between
      species specificity and environmental impacts on the structure of the coral
      associated bacterial community, we conducted an integrated, comparative analysis
      of 44 coral-associated bacterial data sets, including the present study's data.
      The clustering analysis suggests that the influence of spatial and temporal
      factors on the coral-associated bacteria population structure is considerable;
      nonetheless, the effect of species specificity is still detectable in some coral
      species, especially those from the Caribbean Sea.

PMID- 19854922
TI  - beta-Lactam resistance in salmonella strains isolated from retail meats in the
      United States by the National Antimicrobial Resistance Monitoring System between
      2002 and 2006.
AB  - Ampicillin-resistant (Amp(r)) Salmonella enterica isolates (n = 344) representing
      32 serotypes isolated from retail meats from 2002 to 2006 were tested for
      susceptibility to 21 other antimicrobial agents and screened for the presence of
      five beta-lactamase gene families (bla(CMY), bla(TEM), bla(SHV), bla(OXA), and
      bla(CTX-M)) and class 1 integrons. Among the Amp(r) isolates, 66.9% were
      resistant to five or more antimicrobials and 4.9% were resistant to 10 or more
      antimicrobials. Coresistance to other beta-lactams was noted for amoxicillin
      clavulanic acid (55.5%), ceftiofur (50%), cefoxitin (50%), and ceftazidime
      (24.7%), whereas less than 5% of isolates were resistant to piperacillin
      tazobactam (4.9%), cefotaxime (3.5%), ceftriaxone (2%), and aztreonam (1.2%). All
      isolates were susceptible to cefepime, imipenem, and cefquinome. No Salmonella
      producing extended-spectrum beta-lactamases was found in this study.
      Approximately 7% of the isolates displayed a typical multidrug-resistant (MDR)
      AmpC phenotype, with resistance to ampicillin, chloramphenicol, streptomycin,
      sulfonamide, tetracycline, plus resistance to amoxicillin-clavulanic acid,
      cefoxitin, and ceftiofur and with decreased susceptibility to ceftriaxone (MIC >
      or = 4 microg/ml). Pulsed-field gel electrophoresis results showed that several
      MDR clones were geographically dispersed in different types of meats throughout
      the five sampling years. Additionally, 50% of the isolates contained bla(CMY),
      47% carried bla(TEM-1), and 2.6% carried both genes. Only 15% of the isolates
      harbored class I integrons carrying various combinations of aadA, aadB, and dfrA
      gene cassettes. The bla(CMY), bla(TEM), and class 1 integrons were transferable
      through conjugation and/or transformation. Our findings indicate that a varied
      spectrum of coresistance traits is present in Amp(r) Salmonella strains in the
      meat supply of the United States, with a continued predominance of bla(CMY) and
      bla(TEM) genes in beta-lactam-resistant isolates.

PMID- 19854923
TI  - Bradyrhizobia nodulating the Acacia mangium x A. auriculiformis interspecific
      hybrid are specific and differ from those associated with both parental species.
AB  - In the context of an increasing utilization of the interspecific hybrid Acacia
      mangium x A. auriculiformis as a plantation tree in the tropical humid zone, its
      symbiotic characterization was carried out in comparison with that of its two
      parental species. Rhizobium strains of diverse geographical origins were isolated
      from root nodules of the hybrid and its parents. Almost all Acacia hybrid
      isolates were fast growing on yeast extract-mannitol medium, in contrast to those
      isolated from both parental species, which were mostly slow growing. The
      rhizobium strains were characterized through partial sequencing of the rRNA
      operon. In the phylogenetic tree, almost all strains isolated from the hybrid
      were grouped together in a clade close to Bradyrhizobium japonicum, while all
      strains isolated from both parental species were close to Bradyrhizobium elkanii.
      Inoculation experiments performed under in vitro or greenhouse conditions showed
      that all strains were infective with their original hosts but exhibited very
      variable degrees of effectivity according to the host plant tested. Thus,
      homologous strain-host associations were more effective than heterologous ones.
      This shows that there is still a high potential for isolating and testing new
      strains from hybrids to be used as inoculants in the context of large-scale
      afforestation programs.

PMID- 19854924
TI  - Development of a fluorescent in situ method for visualization of enteric viruses.
AB  - Studying the interactions between enteric pathogens and their environment is
      important to improving our understanding of their persistence and transmission.
      However, this remains challenging in large part because of difficulties
      associated with tracking pathogens in their natural environment(s). In this
      study, we report a fluorescent labeling strategy which was applied to murine
      norovirus (MNV-1), a human norovirus surrogate, and hepatitis A virus (HAV).
      Specifically, streptavidin-labeled Quantum dots (Q-Dots) were bound to
      biotinylated capsids of MNV-1 and HAV (bio-MNV-1 and bio-HAV); the process was
      confirmed by using a sandwich-type approach in which streptavidin-bound plates
      were reacted with biotinylated virus followed by a secondary binding to Q-Dots
      with an emission range of 635 to 675 nm (Q-Dots 655). The assay demonstrated a
      relative fluorescence of 528 +/- 48.1 and 112 +/- 8.6 for bio-MNV-1 and control
      MNV-1, respectively. The biotinylation process did not impact virus infectivity,
      nor did it interfere with the interactions between the virus and host cells or
      model produce items. Using fluorescent microscopy, it was possible to visualize
      both bio-HAV and bio-MNV-1 attached to the surfaces of permissive mammalian cells
      and green onion tissue. The method provides a powerful tool for the labeling and
      detection of enteric viruses (and their surrogates) which can be used to track
      virus behavior in situ.

PMID- 19854925
TI  - Genomic characterization of the intron-containing T7-like phage phiL7 of
      Xanthomonas campestris.
AB  - The lytic phage phiL7, which morphologically belongs to the Siphoviridae family,
      infects Xanthomonas campestris pv. campestris. Nucleotide sequence analysis has
      revealed that phiL7 contains a linear double-stranded DNA genome (44,080 bp, 56%
      G+C) with a 3'-protruding cos site (5'-TTACCGGAC-3') and 59 possible genes. Among
      the deduced proteins, 32 have homologs with known functions and 18 show no
      database similarities; moreover, the genes encoding these 18 proteins mostly have
      varying G+C contents and form clusters dispersed along the genome. Only 39 genes
      have sequences related (27% to 78%) to those of sequenced genes of X. oryzae pv.
      oryzae phages, although the genome size and architecture of these Xanthomonas
      phages are similar. These findings suggest that phiL7 acquired genes by
      horizontal transfer, followed by evolution via various types of mutations. Major
      differences were found between phiL7 and the X. oryzae pv. oryzae phages: (i)
      phiL7 has a group I intron inserted in the DNA polymerase gene, the first such
      intron observed in Xanthomonas phages; (ii) although infection of phiL7 exerted
      inhibition to the host RNA polymerase, similar to the situations in X. oryzae pv.
      oryzae phages Xp10 and Xop411, sequence analysis did not identify a homologue of
      the Xp10 p7 that controls the shift from host RNA polymerase (RNAP) to viral RNAP
      during transcription; and (iii) phiL7 lacks the tail fiber protein gene that
      exhibits domain duplications thought to be important for host range determination
      in OP1, and sequence analysis suggested that p20 (tail protein III) instead has
      the potential to play this role.

PMID- 19854926
TI  - Carboxylate transporter gene JEN1 from the entomopathogenic fungus Beauveria
      bassiana is involved in conidiation and virulence.
AB  - Beauveria bassiana is an important entomopathogenic fungus widely used as a
      biological agent to control insect pests. A gene (B. bassiana JEN1 [BbJEN1])
      homologous to JEN1 encoding a carboxylate transporter in Saccharomyces cerevisiae
      was identified in a B. bassiana transfer DNA (T-DNA) insertional mutant.
      Disruption of the gene decreased the carboxylate contents in hyphae, while
      increasing the conidial yield. However, overexpression of this transporter
      resulted in significant increases in carboxylates and decreased the conidial
      yield. BbJEN1 was strongly induced by insect cuticles and highly expressed in the
      hyphae penetrating insect cuticles not in hyphal bodies, suggesting that this
      gene is involved in the early stage of pathogenesis of B. bassiana. The bioassay
      results indicated that disruption of BbJEN1 significantly reduced the virulence
      of B. bassiana to aphids. Compared to the wild type, DeltaBbJEN1 alkalinized the
      insect cuticle to a reduced extent. The alkalinization of the cuticle is a
      physiological signal triggering the production of pathogenicity. Therefore, we
      identified a new factor influencing virulence, which is responsible for the
      alkalinization of the insect cuticle and the initiation of fungal pathogenesis in
      insects.

PMID- 19854927
TI  - Identification of catechin as one of the flavonoids from Combretum albiflorum
      bark extract that reduces the production of quorum-sensing-controlled virulence
      factors in Pseudomonas aeruginosa PAO1.
AB  - Quorum-sensing (QS) regulates the production of key virulence factors in
      Pseudomonas aeruginosa and other important pathogenic bacteria. In this report,
      extracts of leaves and bark of Combretum albiflorum (Tul.) Jongkind
      (Combretaceae) were found to quench the production of QS-dependent factors in P.
      aeruginosa PAO1. Chromatographic fractionation of the crude active extract
      generated several active fractions containing flavonoids, as shown by their
      typical spectral features. Purification and structural characterization of one of
      the active compounds led to the identification of the flavan-3-ol catechin
      [(2R,3S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol]. The
      identity of catechin as one of the active molecules was confirmed by comparing
      the high-pressure liquid chromatography profiles and the mass spectrometry
      spectra obtained for a catechin standard and for the active C. albiflorum
      fraction. Moreover, standard catechin had a significant negative effect on
      pyocyanin and elastase productions and biofilm formation, as well as on the
      expression of the QS-regulated genes lasB and rhlA and of the key QS regulatory
      genes lasI, lasR, rhlI, and rhlR. The use of RhlR- and LasR-based biosensors
      indicated that catechin might interfere with the perception of the QS signal N
      butanoyl-l-homoserine lactone by RhlR, thereby leading to a reduction of the
      production of QS factors. Hence, catechin, along with other flavonoids produced
      by higher plants, might constitute a first line of defense against pathogenic
      attacks by affecting QS mechanisms and thereby virulence factor production.

PMID- 19854928
TI  - Effect of glycosylation and additional domains on the thermostability of a family
      10 xylanase produced by Thermopolyspora flexuosa.
AB  - The effects of different structural features on the thermostability of
      Thermopolyspora flexuosa xylanase XYN10A were investigated. A C-terminal
      carbohydrate binding module had only a slight effect, whereas a polyhistidine tag
      increased the thermostability of XYN10A xylanase. In contrast, glycosylation at
      Asn26, located in an exposed loop, decreased the thermostability of the xylanase.
      The presence of a substrate increased stability mainly at low pH.

PMID- 19854929
TI  - Phage therapy to reduce preprocessing Salmonella infections in market-weight
      swine.
AB  - Contamination of meat products with food-borne pathogens usually results from the
      carcass coming in contact with the feces of an infected animal during processing.
      In the case of Salmonella, pigs can become colonized with the organism during
      transport and lairage from contaminated trailers and holding pens, resulting in
      increased pathogen shedding just prior to processing. Increased shedding, in
      turn, amplifies the likelihood of carcass contamination by magnifying the amount
      of bacteria that enters the processing facility. We conducted a series of
      experiments to test whether phage therapy could limit Salmonella infections at
      this crucial period. In a preliminary experiment done with small pigs (3 to 4
      weeks old; 30 to 40 lb), administration of an anti-Salmonella phage cocktail at
      the time of inoculation with Salmonella enterica serovar Typhimurium reduced
      Salmonella colonization by 99.0 to 99.9% (2- to 3-log reduction) in the tonsils,
      ileum, and cecum. To test the efficacy of phage therapy in a production-like
      setting, we inoculated four market-weight pigs (in three replicates) with
      Salmonella enterica serovar Typhimurium and allowed the challenged pigs to
      contaminate a holding pen for 48 h. Sixteen naive pigs were randomly split into
      two groups which received either the anti-Salmonella phage cocktail or a mock
      treatment. Both groups of pigs were comingled with the challenged pigs in the
      contaminated pen. Treatment with the anti-Salmonella phage cocktail significantly
      reduced cecal Salmonella concentrations (95%; P<0.05) while also reducing
      (numerically) ileal Salmonella concentrations (90%; P=0.06). Additional in vitro
      studies showed that the phage cocktail was also lytic against several non
      Typhimurium serovars.

PMID- 19854931
TI  - Contribution of microbial activity to carbon chemistry in clouds.
AB  - The biodegradation of the most abundant atmospheric organic C1 to C4 compounds
      (formate, acetate, lactate, succinate) by five selected representative microbial
      strains (three Pseudomonas strains, one Sphingomonas strain, and one yeast
      strain) isolated from cloud water at the puy de Dome has been studied.
      Experiments were first conducted under model conditions and consisted of a pure
      strain incubated in the presence of a single organic compound. Kinetics showed
      the ability of the isolates to degrade atmospheric compounds at temperatures
      representative of low-altitude clouds (5 degrees C and 17 degrees C). Then, to
      provide data that can be extrapolated to real situations, microcosm experiments
      were developed. A solution that chemically mimicked the composition of cloud
      water was used as an incubation medium for microbial strains. Under these
      conditions, we determined that microbial activity would significantly contribute
      to the degradation of formate, acetate, and succinate in cloud water at 5 degrees
      C and 17 degrees C, with lifetimes of 0.4 to 69.1 days. Compared with the
      reactivity involving free radicals, our results suggest that biological activity
      drives the oxidation of carbonaceous compounds during the night (90 to 99%),
      while its contribution accounts for 2 to 37% of the reactivity during the day,
      competing with photochemistry.

PMID- 19854930
TI  - Insights into the evolution of macrolactam biosynthesis through cloning and
      comparative analysis of the biosynthetic gene cluster for a novel macrocyclic
      lactam, ML-449.
AB  - A new compound, designated ML-449, structurally similar to the known 20-membered
      macrolactam BE-14106, was isolated from a marine sediment-derived Streptomyces
      sp. Cloning and sequencing of the 83-kb ML-449 biosynthetic gene cluster revealed
      its high level of similarity to the BE-14106 gene cluster. Comparison of the
      respective biosynthetic pathways indicated that the difference in the compounds'
      structures stems from the incorporation of one extra acetate unit during the
      synthesis of the acyl side chain. A phylogenetic analysis of the beta
      ketosynthase (KS) domains from polyketide synthases involved in the biosynthesis
      of macrolactams pointed to a common ancestry for the two clusters. Furthermore,
      the analysis demonstrated the formation of a macrolactam-specific subclade for
      the majority of the KS domains from several macrolactam-biosynthetic gene
      clusters, indicating a closer relationship between macrolactam clusters than with
      the macrolactone clusters included in the analysis. Some KS domains from the ML
      449, BE-14106, and salinilactam gene clusters did, however, show a closer
      relationship with KS domains from the polyene macrolide clusters, suggesting
      potential acquisition rather than duplication of certain PKS genes. Comparison of
      the ML-449, BE-14106, vicenistatin, and salinilactam biosynthetic gene clusters
      indicated an evolutionary relationship between them and provided new insights
      into the processes governing the evolution of small-ring macrolactam
      biosynthesis.

PMID- 19854932
TI  - Distribution of in vitro fermentation ability of lacto-N-biose I, a major
      building block of human milk oligosaccharides, in bifidobacterial strains.
AB  - This study investigated the potential utilization of lacto-N-biose I (LNB) by
      individual strains of bifidobacteria. LNB is a building block for the human milk
      oligosaccharides, which have been suggested to be a factor for selective growth
      of bifidobacteria. A total of 208 strains comprising 10 species and 4 subspecies
      were analyzed for the presence of the galacto-N-biose/lacto-N-biose I
      phosphorylase (GLNBP) gene (lnpA) and examined for growth when LNB was used as
      the sole carbohydrate source. While all strains of Bifidobacterium longum subsp.
      longum, B. longum subsp. infantis, B. breve, and B. bifidum were able to grow on
      LNB, none of the strains of B. adolescentis, B. catenulatum, B. dentium, B.
      angulatum, B. animalis subsp. lactis, and B. thermophilum showed any growth. In
      addition, some strains of B. pseudocatenulatum, B. animalis subsp. animalis, and
      B. pseudolongum exhibited the ability to utilize LNB. With the exception for B.
      pseudocatenulatum, the presence of lnpA coincided with LNB utilization in almost
      all strains. These results indicate that bifidobacterial species, which are the
      predominant species found in infant intestines, are potential utilizers of LNB.
      These findings support the hypothesis that GLNBP plays a key role in the
      colonization of bifidobacteria in the infant intestine.

PMID- 19854933
TI  - SALAD database: a motif-based database of protein annotations for plant
      comparative genomics.
AB  - Proteins often have several motifs with distinct evolutionary histories. Proteins
      with similar motifs have similar biochemical properties and thus related
      biological functions. We constructed a unique comparative genomics database
      termed the SALAD database (http://salad.dna.affrc.go.jp/salad/) from plant-genome
      based proteome data sets. We extracted evolutionarily conserved motifs by MEME
      software from 209,529 protein-sequence annotation groups selected by BLASTP from
      the proteome data sets of 10 species: rice, sorghum, Arabidopsis thaliana, grape,
      a lycophyte, a moss, 3 algae, and yeast. Similarity clustering of each protein
      group was performed by pairwise scoring of the motif patterns of the sequences.
      The SALAD database provides a user-friendly graphical viewer that displays a
      motif pattern diagram linked to the resulting bootstrapped dendrogram for each
      protein group. Amino-acid-sequence-based and nucleotide-sequence-based
      phylogenetic trees for motif combination alignment, a logo comparison diagram for
      each clade in the tree, and a Pfam-domain pattern diagram are also available. We
      also developed a viewer named 'SALAD on ARRAYs' to view arbitrary microarray data
      sets of paralogous genes linked to the same dendrogram in a window. The SALAD
      database is a powerful tool for comparing protein sequences and can provide
      valuable hints for biological analysis.

PMID- 19854934
TI  - DNA adducts of aristolochic acid II: total synthesis and site-specific
      mutagenesis studies in mammalian cells.
AB  - Aristolochic acids I and II (AA-I, AA-II) are found in all Aristolochia species.
      Ingestion of these acids either in the form of herbal remedies or as contaminated
      wheat flour causes a dose-dependent chronic kidney failure characterized by renal
      tubulointerstitial fibrosis. In approximately 50% of these cases, the condition
      is accompanied by an upper urinary tract malignancy. The disease is now termed
      aristolochic acid nephropathy (AAN). AA-I is largely responsible for the
      nephrotoxicity while both AA-I and AA-II are genotoxic. DNA adducts derived from
      AA-I and AA-II have been isolated from renal tissues of patients suffering from
      AAN. We describe the total synthesis, de novo, of the dA and dG adducts derived
      from AA-II, their incorporation site-specifically into DNA oligomers and the
      splicing of these modified oligomers into a plasmid construct followed by
      transfection into mouse embryonic fibroblasts. Analysis of the plasmid progeny
      revealed that both adducts blocked replication but were still partly processed by
      DNA polymerase(s). Although the majority of coding events involved insertion of
      correct nucleotides, substantial misincorporation of bases also was noted. The dA
      adduct is significantly more mutagenic than the dG adduct; both adducts give
      rise, almost exclusively, to misincorporation of dA, which leads to AL-II-dA-->T
      and AL-II-dG-->T transversions.

PMID- 19854935
TI  - Understanding how the crowded interior of cells stabilizes DNA/DNA and DNA/RNA
      hybrids-in silico predictions and in vitro evidence.
AB  - Amplification of DNA in vivo occurs in intracellular environments characterized
      by macromolecular crowding (MMC). In vitro Polymerase-chain-reaction (PCR),
      however, is non-crowded, requires thermal cycling for melting of DNA strands,
      primer-template hybridization and enzymatic primer-extension. The temperature
      optima for primer-annealing and extension are strikingly disparate which predicts
      primers to dissociate from template during extension thereby compromising PCR
      efficiency. We hypothesized that MMC is not only important for the extension
      phase in vivo but also during PCR by stabilizing nucleotide hybrids. Novel
      atomistic Molecular Dynamics simulations elucidated that MMC stabilizes hydrogen
      bonding between complementary nucleotides. Real-time PCR under MMC confirmed that
      melting-temperatures of complementary DNA-DNA and DNA-RNA hybrids increased by up
      to 8 degrees C with high specificity and high duplex-preservation after extension
      (71% versus 37% non-crowded). MMC enhanced DNA hybrid-helicity, and drove
      specificity of duplex formation preferring matching versus mismatched sequences,
      including hair-pin-forming DNA- single-strands.

PMID- 19854936
TI  - MouseBook: an integrated portal of mouse resources.
AB  - The MouseBook (http://www.mousebook.org) databases and web portal provide access
      to information about mutant mouse lines held as live or cryopreserved stocks at
      MRC Harwell. The MouseBook portal integrates curated information from the MRC
      Harwell stock resource, and other Harwell databases, with information from
      external data resources to provide value-added information above and beyond what
      is available through other routes such as International Mouse Stain Resource
      (IMSR). MouseBook can be searched either using an intuitive Google style free
      text search or using the Mammalian Phenotype (MP) ontology tree structure. Text
      searches can be on gene, allele, strain identifier (e.g. MGI ID) or phenotype
      term and are assisted by automatic recognition of term types and autocompletion
      of gene and allele names covered by the database. Results are returned in a
      tabbed format providing categorized results identified from each of the catalogs
      in MouseBook. Individual result lines from each catalog include information on
      gene, allele, chromosomal location and phenotype, and provide a simple click
      through link to further information as well as ordering the strain. The
      infrastructure underlying MouseBook has been designed to be extensible, allowing
      additional data sources to be added and enabling other sites to make their data
      directly available through MouseBook.

PMID- 19854937
TI  - Enhanced gene repair mediated by methyl-CpG-modified single-stranded
      oligonucleotides.
AB  - Gene editing mediated by oligonucleotides has been shown to induce stable single
      base alterations in genomic DNA in both prokaryotic and eukaryotic organisms.
      However, the low frequencies of gene repair have limited its applicability for
      both basic manipulation of genomic sequences and for the development of
      therapeutic approaches for genetic disorders. Here, we show that single-stranded
      oligodeoxynucleotides (ssODNs) containing a methyl-CpG modification and capable
      of binding to the methyl-CpG binding domain protein 4 (MBD4) are able to induce
      >10-fold higher levels of gene correction than ssODNs lacking the specific
      modification. Correction was stably inherited through cell division and was
      confirmed at the protein, transcript and genomic levels. Downregulation of MBD4
      expression using RNAi prevented the enhancement of gene correction efficacy
      obtained using the methyl-CpG-modified ssODN, demonstrating the specificity of
      the repair mechanism being recruited. Our data demonstrate that efficient
      manipulation of genomic targets can be achieved and controlled by the type of
      ssODN used and by modulation of the repair mechanism involved in the correction
      process. This new generation of ssODNs represents an important technological
      advance that is likely to have an impact on multiple applications, especially for
      gene therapy where permanent correction of the genetic defect has clear
      advantages over viral and other nonviral approaches currently being tested.

PMID- 19854938
TI  - Efficient gene silencing by delivery of locked nucleic acid antisense
      oligonucleotides, unassisted by transfection reagents.
AB  - For the past 15-20 years, the intracellular delivery and silencing activity of
      oligodeoxynucleotides have been essentially completely dependent on the use of a
      delivery technology (e.g. lipofection). We have developed a method (called
      'gymnosis') that does not require the use of any transfection reagent or any
      additives to serum whatsoever, but rather takes advantage of the normal growth
      properties of cells in tissue culture in order to promote productive
      oligonucleotide uptake. This robust method permits the sequence-specific
      silencing of multiple targets in a large number of cell types in tissue culture,
      both at the protein and mRNA level, at concentrations in the low micromolar
      range. Optimum results were obtained with locked nucleic acid (LNA)
      phosphorothioate gap-mers. By appropriate manipulation of oligonucleotide dosing,
      this silencing can be continuously maintained with little or no toxicity for >240
      days. High levels of oligonucleotide in the cell nucleus are not a requirement
      for gene silencing, contrary to long accepted dogma. In addition, gymnotic
      delivery can efficiently deliver oligonucleotides to suspension cells that are
      known to be very difficult to transfect. Finally, the pattern of gene silencing
      of in vitro gymnotically delivered oligonucleotides correlates particularly well
      with in vivo silencing. The establishment of this link is of particular
      significance to those in the academic research and drug discovery and development
      communities.

PMID- 19854939
TI  - BioNumbers--the database of key numbers in molecular and cell biology.
AB  - BioNumbers (http://www.bionumbers.hms.harvard.edu) is a database of key numbers
      in molecular and cell biology--the quantitative properties of biological systems
      of interest to computational, systems and molecular cell biologists. Contents of
      the database range from cell sizes to metabolite concentrations, from reaction
      rates to generation times, from genome sizes to the number of mitochondria in a
      cell. While always of importance to biologists, having numbers in hand is
      becoming increasingly critical for experimenting, modeling, and analyzing
      biological systems. BioNumbers was motivated by an appreciation of how long it
      can take to find even the simplest number in the vast biological literature. All
      numbers are taken directly from a literature source and that reference is
      provided with the number. BioNumbers is designed to be highly searchable and
      queries can be performed by keywords or browsed by menus. BioNumbers is a
      collaborative community platform where registered users can add content and make
      comments on existing data. All new entries and commentary are curated to maintain
      high quality. Here we describe the database characteristics and implementation,
      demonstrate its use, and discuss future directions for its development.

PMID- 19854940
TI  - MMBGX: a method for estimating expression at the isoform level and detecting
      differential splicing using whole-transcript Affymetrix arrays.
AB  - Affymetrix has recently developed whole-transcript GeneChips-'Gene' and 'Exon'
      arrays-which interrogate exons along the length of each gene. Although each probe
      on these arrays is intended to hybridize perfectly to only one transcriptional
      target, many probes match multiple transcripts located in different parts of the
      genome or alternative isoforms of the same gene. Existing statistical methods for
      estimating expression do not take this into account and are thus prone to
      producing inflated estimates. We propose a method, Multi-Mapping Bayesian Gene
      eXpression (MMBGX), which disaggregates the signal at 'multi-match' probes. When
      applied to Gene arrays, MMBGX removes the upward bias of gene-level expression
      estimates. When applied to Exon arrays, it can further disaggregate the signal
      between alternative transcripts of the same gene, providing expression estimates
      of individual splice variants. We demonstrate the performance of MMBGX on
      simulated data and a tissue mixture data set. We then show that MMBGX can
      estimate the expression of alternative isoforms within one experimental
      condition, confirming our results by RT-PCR. Finally, we show that our method for
      detecting differential splicing has a lower error rate than standard exon-level
      approaches on a previously validated colon cancer data set.

PMID- 19854942
TI  - Profiling the selectivity of DNA ligases in an array format with mass
      spectrometry.
AB  - This article describes a method for the global profiling of the substrate
      specificities of DNA ligases and illustrates examples using the Taq and T4 DNA
      ligases. The method combines oligonucleotide arrays, which offer the benefits of
      high throughput and multiplexed assays, with mass spectrometry to permit label
      free assays of ligase activity. Arrays were prepared by immobilizing ternary
      biotin-tagged DNA substrates to a self-assembled monolayer presenting a layer of
      streptavidin protein. The array represented complexes having all possible matched
      and mismatched base pairs at the 3' side of the nick site and also included a
      number of deletions and insertions at this site. The arrays were treated with
      ligases and adenosine triphosphate or analogs of the nucleotide triphosphate and
      then analyzed by matrix-assisted laser desorption-ionization mass spectrometry to
      determine the yields for both adenylation of the 5'-probe strand and joining of
      the two probe strands. The resulting activity profiles reveal the basis for
      specificity of the ligases and also point to strategies that use ATP analogs to
      improve specificity. This work introduces a method that can be applied to profile
      a broad range of enzymes that operate on nucleic acid substrates.

PMID- 19854941
TI  - Limited complementarity between U1 snRNA and a retroviral 5' splice site permits
      its attenuation via RNA secondary structure.
AB  - Multiple types of regulation are used by cells and viruses to control alternative
      splicing. In murine leukemia virus, accessibility of the 5' splice site (ss) is
      regulated by an upstream region, which can fold into a complex RNA stem-loop
      structure. The underlying sequence of the structure itself is negligible, since
      most of it could be functionally replaced by a simple heterologous RNA stem-loop
      preserving the wild-type splicing pattern. Increasing the RNA duplex formation
      between U1 snRNA and the 5'ss by a compensatory mutation in position +6 led to
      enhanced splicing. Interestingly, this mutation affects splicing only in the
      context of the secondary structure, arguing for a dynamic interplay between
      structure and primary 5'ss sequence. The reduced 5'ss accessibility could also be
      counteracted by recruiting a splicing enhancer domain via a modified MS2 phage
      coat protein to a single binding site at the tip of the simple RNA stem-loop. The
      mechanism of 5'ss attenuation was revealed using hyperstable U1 snRNA mutants,
      showing that restricted U1 snRNP access is the cause of retroviral alternative
      splicing.

PMID- 19854943
TI  - CpG_MI: a novel approach for identifying functional CpG islands in mammalian
      genomes.
AB  - CpG islands (CGIs) are CpG-rich regions compared to CpG-depleted bulk DNA of
      mammalian genomes and are generally regarded as the epigenetic regulatory regions
      in association with unmethylation, promoter activity and histone modifications.
      Accurate identification of CpG islands with epigenetic regulatory function in
      bulk genomes is of wide interest. Here, the common features of functional CGIs
      are identified using an average mutual information method to differentiate
      functional CGIs from the remaining CGIs. A new approach (CpG mutual information,
      CpG_MI) was further explored to identify functional CGIs based on the cumulative
      mutual information of physical distances between two neighboring CpGs. Compared
      to current approaches, CpG_MI achieved the highest prediction accuracy. This
      approach also identified new functional CGIs overlapping with gene promoter
      regions which were missed by other algorithms. Nearly all CGIs identified by
      CpG_MI overlapped with histone modification marks. CpG_MI could also be used to
      identify potential functional CGIs in other mammalian genomes, as the CpG
      dinucleotide contents and cumulative mutual information distributions are almost
      the same among six mammalian genomes in our analysis. It is a reliable
      quantitative tool for the identification of functional CGIs from bulk genomes and
      helps in understanding the relationships between genomic functional elements and
      epigenomic modifications.

PMID- 19854944
TI  - The NCBI BioSystems database.
AB  - The NCBI BioSystems database, found at http://www.ncbi.nlm.nih.gov/biosystems/,
      centralizes and cross-links existing biological systems databases, increasing
      their utility and target audience by integrating their pathways and systems into
      NCBI resources. This integration allows users of NCBI's Entrez databases to
      quickly categorize proteins, genes and small molecules by metabolic pathway,
      disease state or other BioSystem type, without requiring time-consuming inference
      of biological relationships from the literature or multiple experimental
      datasets.

PMID- 19854945
TI  - Fine tuning of the E. coli NusB:NusE complex affinity to BoxA RNA is required for
      processive antitermination.
AB  - Phage lambda propagation in Escherichia coli host cells requires transcription
      antitermination on the lambda chromosome mediated by lambdaN protein and four
      host Nus factors, NusA, B, E (ribosomal S10) and G. Interaction of E. coli
      NusB:NusE heterodimer with the single stranded BoxA motif of lambdanutL or
      lambdanutR RNA is crucial for this reaction. Similarly, binding of NusB:NusE to a
      BoxA motif is essential to suppress transcription termination in the ribosomal
      RNA (rrn) operons. We used fluorescence anisotropy to measure the binding
      properties of NusB and of NusB:NusE heterodimer to BoxA-containing RNAs differing
      in length and sequence. Our results demonstrate that BoxA is necessary and
      sufficient for binding. We also studied the gain-of-function D118N NusB mutant
      that allows lambda growth in nusA1 or nusE71 mutants. In vivo lambda burst-size
      determinations, CD thermal unfolding measurements and X-ray crystallography of
      this as well as various other NusB D118 mutants showed the importance of size and
      polarity of amino acid 118 for RNA binding and other interactions. Our work
      suggests that the affinity of the NusB:NusE complex to BoxA RNA is precisely
      tuned to maximize control of transcription termination.

PMID- 19854946
TI  - DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase
      II from promoter-proximal pause site, antisense transcription and histone
      acetylation at the human HIF-1alpha gene locus.
AB  - Top1 inhibition by camptothecin (CPT) perturbs RNA polymerase II (Pol II) density
      at promoters and along transcribed genes suggesting an involvement of Top1 in Pol
      II pausing. Here, we demonstrate that Top1 inhibition favors Pol II escape from a
      promoter-proximal pausing site of the human HIF-1alpha gene in living cells.
      Interestingly, alternative splicing at exon 11 was markedly altered in nascent
      HIF-1alpha mRNAs, and chromatin structure was also affected with enhanced histone
      acetylation and reduced nucleosome density in a manner dependent on cdk activity.
      Moreover, CPT increases transcription of a novel long RNA (5'aHIF1alpha),
      antisense to human HIF-1alpha mRNA, and a known antisense RNA at the 3'-end of
      the gene, while decreasing mRNA levels under normoxic and hypoxic conditions. The
      effects require Top1, but are independent from Top1-induced replicative DNA
      damage. Chromatin RNA immunoprecipitation results showed that CPT can activate
      antisense transcription mediated by cyclin-dependent kinase (cdk) activity. Thus,
      Top1 inhibition can trigger a transcriptional stress, involving antisense
      transcription and increased chromatin accessibility, which is dependent on cdk
      activity and deregulated Pol II pausing. A changed balance of antisense
      transcripts and mRNAs may then lead to altered regulation of HIF-1alpha activity
      in human cancer cells.

PMID- 19854947
TI  - FtsK translocation on DNA stops at XerCD-dif.
AB  - Escherichia coli FtsK is a powerful, fast, double-stranded DNA translocase, which
      can strip proteins from DNA. FtsK acts in the late stages of chromosome
      segregation by facilitating sister chromosome unlinking at the division septum.
      KOPS-guided DNA translocation directs FtsK towards dif, located within the
      replication terminus region, ter, where FtsK activates XerCD site-specific
      recombination. Here we show that FtsK translocation stops specifically at XerCD
      dif, thereby preventing removal of XerCD from dif and allowing activation of
      chromosome unlinking by recombination. Stoppage of translocation at XerCD-dif is
      accompanied by a reduction in FtsK ATPase and is not associated with FtsK
      dissociation from DNA. Specific stoppage at recombinase-DNA complexes does not
      require the FtsKgamma regulatory subdomain, which interacts with XerD, and is not
      dependent on either recombinase-mediated DNA cleavage activity, or the formation
      of synaptic complexes.

PMID- 19854948
TI  - The neurofibromatosis type I pre-mRNA is a novel target of CELF protein-mediated
      splicing regulation.
AB  - The CUG-BP and ETR-3 like factors (CELF) are a family of six highly conserved RNA
      binding proteins that preferentially bind to UG-rich sequences. One of the key
      functions of these proteins is to mediate alternative splicing in a number of
      tissues, including brain, heart and muscle. To fully understand the function of
      CELF proteins, it is important to identify downstream targets of CELF proteins.
      In this communication, we report that neurofibromatosis type I (NF1) exon 23a is
      a novel target of CELF protein-mediated splicing regulation in neuron-like cells.
      NF1 regulates Ras signaling, and the isoform that excludes exon 23a shows 10
      times greater ability to down-regulate Ras signaling than the isoform that
      includes exon 23a. Five of the six CELF proteins strongly suppress the inclusion
      of NF1 exon 23a. Over-expression or siRNA knockdown of these proteins in cell
      transfection experiments altered the levels of NF1 exon 23a inclusion. In vitro
      binding and splicing analyses demonstrate that CELF proteins block splicing
      through interfering with binding of U2AF(65). These studies, combined with our
      previous investigations demonstrating a role for Hu proteins and TIA-1/TIAR in
      controlling NF1 exon 23a inclusion, highlight the complex nature of regulation of
      this important alternative splicing event.

PMID- 19854949
TI  - Maximization of negative correlations in time-course gene expression data for
      enhancing understanding of molecular pathways.
AB  - Positive correlation can be diversely instantiated as shifting, scaling or
      geometric pattern, and it has been extensively explored for time-course gene
      expression data and pathway analysis. Recently, biological studies emerge a trend
      focusing on the notion of negative correlations such as opposite expression
      patterns, complementary patterns and self-negative regulation of transcription
      factors (TFs). These biological ideas and primitive observations motivate us to
      formulate and investigate the problem of maximizing negative correlations. The
      objective is to discover all maximal negative correlations of statistical and
      biological significance from time-course gene expression data for enhancing our
      understanding of molecular pathways. Given a gene expression matrix, a maximal
      negative correlation is defined as an activation-inhibition two-way expression
      pattern (AIE pattern). We propose a parameter-free algorithm to enumerate the
      complete set of AIE patterns from a data set. This algorithm can identify
      significant negative correlations that cannot be identified by the traditional
      clustering/biclustering methods. To demonstrate the biological usefulness of AIE
      patterns in the analysis of molecular pathways, we conducted deep case studies
      for AIE patterns identified from Yeast cell cycle data sets. In particular, in
      the analysis of the Lysine biosynthesis pathway, new regulation modules and
      pathway components were inferred according to a significant negative correlation
      which is likely caused by a co-regulation of the TFs at the higher layer of the
      biological network. We conjecture that maximal negative correlations between
      genes are actually a common characteristic in molecular pathways, which can
      provide insights into the cell stress response study, drug response evaluation,
      etc.

PMID- 19854950
TI  - 'RNA walk' a novel approach to study RNA-RNA interactions between a small RNA and
      its target.
AB  - In this study we describe a novel method to investigate the RNA-RNA interactions
      between a small RNA and its target that we termed 'RNA walk'. The method is based
      on UV-induced AMT cross-linking in vivo followed by affinity selection of the
      hybrid molecules and mapping the intermolecular adducts by RT-PCR or real-time
      PCR. Domains carrying the cross-linked adducts fail to efficiently amplify by PCR
      compared with non-cross-linked domains. This method was calibrated and used to
      study the interaction between a special tRNA-like molecule (sRNA-85) that is part
      of the trypanosome signal recognition particle (SRP) complex and the ribosome.
      Four contact sites between sRNA-85 and rRNA were identified by 'RNA walk' and
      were further fine-mapped by primer extension. Two of the contact sites are
      expected; one contact site mimics the interaction of the mammalian Alu domain of
      SRP with the ribosome and the other contact sites include a canonical tRNA
      interaction. The two other cross-linked sites could not be predicted. We propose
      that 'RNA walk, is a generic method to map target RNA small RNAs interactions in
      vivo.

PMID- 19854951
TI  - Chemical Entities of Biological Interest: an update.
AB  - Chemical Entities of Biological Interest (ChEBI) is a freely available dictionary
      of molecular entities focused on 'small' chemical compounds. The molecular
      entities in question are either natural products or synthetic products used to
      intervene in the processes of living organisms. Genome-encoded macromolecules
      (nucleic acids, proteins and peptides derived from proteins by cleavage) are not
      as a rule included in ChEBI. In addition to molecular entities, ChEBI contains
      groups (parts of molecular entities) and classes of entities. ChEBI includes an
      ontological classification, whereby the relationships between molecular entities
      or classes of entities and their parents and/or children are specified. ChEBI is
      available online at http://www.ebi.ac.uk/chebi/. This article reports on new
      features in ChEBI since the last NAR report in 2007, including substructure and
      similarity searching, a submission tool for authoring of ChEBI datasets by the
      community and a 30-fold increase in the number of chemical structures stored in
      ChEBI.

PMID- 19854952
TI  - Drosophila mini-white model system: new insights into positive position effects
      and the role of transcriptional terminators and gypsy insulator in transgene
      shielding.
AB  - The white gene, which is responsible for eye pigmentation, is widely used to
      study position effects in Drosophila. As a result of insertion of P-element
      vectors containing mini-white without enhancers into random chromosomal sites,
      flies with different eye color phenotypes appear, which is usually explained by
      the influence of positive/negative regulatory elements located around the
      insertion site. We found that, in more than 70% of cases when mini-white
      expression was subject to positive position effects, deletion of the white
      promoter had no effect on eye pigmentation; in these cases, the transposon was
      inserted into the transcribed regions of genes. Therefore, transcription through
      the mini-white gene could be responsible for high levels of its expression in
      most of chromosomal sites. Consistently with this conclusion, transcriptional
      terminators proved to be efficient in protecting mini-white expression from
      positive position effects. On the other hand, the best characterized Drosophila
      gypsy insulator was poorly effective in terminating transcription and, as a
      consequence, only partially protected mini-white expression from these effects.
      Thus, to ensure maximum protection of a transgene from position effects, a
      perfect boundary/insulator element should combine three activities: to block
      enhancers, to provide a barrier between active and repressed chromatin, and to
      terminate transcription.

PMID- 19854953
TI  - Birth of mucus.

PMID- 19854955
TI  - Morphological changes in murine skeletal muscle in response to exercise and
      mesterolone.
AB  - Light and electron microscopy and quantitative morphometry were used to determine
      the effects of exercise and mesterolone on the soleus muscles of mice. Both
      exercise and mesterolone caused a significant hypertrophy of extrafusal muscle
      fibres. The hypertrophy of Type I fibres was greater than that of Type II fibres.
      There was no hyperplasia. Mitochondria were more numerous and larger than in the
      muscles of sedentary animals. Capillarity increased and small centrally nucleated
      muscle fibres appeared, usually in small clusters and most often in the muscles
      of animals exposed to mesterolone. A small proportion of satellite cells
      exhibited signs of activation but there were more in the muscles of mesterolone
      treated animals than after exercise. Muscles from animals that had been both
      exercised and treated with mesterolone exhibited the largest changes: muscle mass
      and muscle fibre hypertrophy was greater than in all other groups of animals,
      capillarity was higher and >30% of all recognized satellite cells exhibited signs
      of activation. Groups of small centrally nucleated muscle fibres were commonly
      seen in these muscles. They appeared to be the result of splits in the form of
      sprouts from existing muscle fibres. With both exercise and mesterolone, alone or
      in combination, there was an increase in the proportion of Type I muscle fibres
      and a decrease in the proportion of Type II.

PMID- 19854954
TI  - Prolonged mechanical ventilation with air induces apoptosis and causes failure of
      alveolar septation and angiogenesis in lungs of newborn mice.
AB  - Defective lung septation and angiogenesis, quintessential features of neonatal
      chronic lung disease (CLD), typically result from lengthy exposure of developing
      lungs to mechanical ventilation (MV) and hyperoxia. Previous studies showed fewer
      alveoli and microvessels, with reduced VEGF and increased transforming growth
      factor-beta (TGFbeta) signaling, and excess, scattered elastin in lungs of
      premature infants and lambs with CLD vs. normal controls. MV of newborn mice with
      40% O(2) for 24 h yielded similar lung structural abnormalities linked to
      impaired VEGF signaling, dysregulated elastin production, and increased
      apoptosis. These studies could not determine the relative importance of cyclic
      stretch vs. hyperoxia in causing these lung growth abnormalities. We therefore
      studied the impact of MV for 24 h with air on alveolar septation (quantitative
      lung histology), angiogenesis [CD31 quantitative-immunohistochemistry (IHC),
      immunoblots], apoptosis [TdT-mediated dUTP nick end labeling (TUNEL), active
      caspase-3 assays], VEGF signaling [VEGF-A, VEGF receptor 1 (VEGF-R1), VEGF-R2
      immunoblots], TGFbeta activation [phosphorylated Smad2 (pSmad2) quantitative
      IHC], and elastin production (tropoelastin immunoblots, quantitative image
      analysis of Hart's stained sections) in lungs of 6-day-old mice. Compared with
      unventilated controls, MV caused a 3-fold increase in alveolar area,
      approximately 50% reduction in alveolar number and endothelial surface area, >5
      fold increase in apoptosis, >50% decrease in lung VEGF-R2 protein, 4-fold
      increase of pSmad2 protein, and >50% increase in lung elastin, which was
      distributed throughout alveolar walls rather than at septal tips. This study is
      the first to show that prolonged MV of developing lungs, without associated
      hyperoxia, can inhibit alveolar septation and angiogenesis and increase apoptosis
      and lung elastin, findings that could reflect stretch-induced changes in VEGF and
      TGFbeta signaling, as reported in CLD.

PMID- 19854956
TI  - Utility of sonography for evaluation of clinical T1 and T2 glottic carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic impact of
      sonographically determined tumor features in relation to local control of
      clinical T1 and T2 glottic carcinoma treated by definitive radiation therapy.
      METHODS: Between 1999 and 2005, 72 patients with T1 and T2 glottic carcinoma were
      evaluated by percutaneous sonography in terms of tumor detectability, maximum
      tumor dimension, involvement of the anterior commissure, presence of
      supraglottic, subglottic, or paraglottic spread, and thyroid cartilage invasion.
      Factor analyses for local control included clinical features, sonographic
      findings, and treatment factors. RESULTS: Forty-one lesions (57%) were detected
      as hypoechoic masses on sonography. For detectable T2 tumors, sonographic and
      laryngoscopic findings were in agreement in all cases with respect to spread to
      anatomic subsites. The 3-year local control rate with radiation therapy alone was
      82%. Univariate analysis of the sonographic characteristics revealed that the
      maximum tumor dimension and thyroid cartilage invasion predicted a loss of local
      control, whereas none of the clinical or treatment characteristics was
      significant. Multivariate analysis showed that thyroid cartilage invasion was an
      independent negative prognostic factor for local control. CONCLUSIONS: Sonography
      provides information about the likely outcome of radiation therapy for patients
      with clinical T2 glottic carcinoma, although its utility for T1 lesions is not
      proven. Thyroid cartilage invasion may be an independent negative predictor of
      the outcome.

PMID- 19854957
TI  - Sonographic depiction of trigger fingers in acromegaly.
AB  - OBJECTIVE: The purpose of this study was to compare the prevalence of trigger
      fingers in patients with acromegaly versus an unaffected control group. METHODS:
      This study was performed with Institutional Review Board approval, and informed
      written consent was obtained from each patient and control participant. The
      diagnosis was made by a combination of clinical symptoms and sonographically
      measured thickening of the first annular (A1) pulley. The A1 pulley thickness was
      measured in 40 patients and 40 control participants by means of a 17-5 MHz high
      resolution transducer. Thickening of the A1 pulley and abnormalities of the
      underlying flexor tendons associated with the clinical sign were diagnostic for a
      trigger finger. The acromegalic patients were divided into groups according to
      disease activity and therapy. The study was performed at the baseline and at a
      follow-up after 1 year. RESULTS: At the baseline, clinical and sonographic
      findings were consistent with trigger fingers in 25% of patients (6 at
      presentation and 4 with uncontrolled disease). After 1 year, the trigger fingers
      recovered in the patients who were not receiving any treatment at the beginning
      of the study. In patients with uncontrolled disease, the condition remained
      unchanged. The A1 pulley thickness was greater in the acromegalic patients than
      control participants (mean +/- SD, 0.44 +/- 0.19 versus 0.24 +/- 0.05 mm; P <
      .05). In the patients treated for acromegaly, the trigger fingers disappeared,
      and a reduction in the A1 pulley thickness was noted (P < .05) at the follow-up.
      CONCLUSIONS: Trigger fingers were observed in 25% of the acromegalic patients but
      in none of the control participants. The A1 pulley was significantly thicker in
      the acromegalic patients and normalized after 1 year in some who were treated for
      the disease.

PMID- 19854958
TI  - Posttraumatic painful hip: sonography as a screening test for occult hip
      fractures.
AB  - OBJECTIVE: Nondisplaced hip fractures may be radiographically occult and require
      magnetic resonance imaging (MRI) or bone scintigraphy for diagnosis. Both
      examinations are expensive and are not readily available in many hospitals. Our
      objective was to evaluate sonography as a screening tool for occult hip fractures
      in posttraumatic painful hips in elderly patients. METHODS: We prospectively
      evaluated 30 patients (mean age, 73 years), who were admitted for painful hips
      after having low-energy trauma with nondiagnostic hip radiographs. After
      inclusion, patients underwent sonography of both hips for signs of injury. After
      completion of the sonographic examination and analysis of the results, patients
      underwent MRI of both hips. The sonographic findings were compared with the MRI
      findings, which served as the reference standard for accurate detection of a hip
      fracture. RESULTS: Ten hip fractures were diagnosed by MRI. Sonography showed
      trauma-related changes in all of those patients and in 7 additional patients, 3
      of whom had pubic fractures. Sonography correctly identified 13 patients without
      hip fractures. The sensitivity of sonography was found to be 100%, whereas the
      specificity for hip fractures was 65%. CONCLUSIONS: Sonography for posttraumatic
      hip pain with negative radiographic findings did not result in a single missed
      hip fracture. Therefore, sonography may serve as an effective screening tool,
      mandating MRI only for cases with positive findings, whereas patients with
      negative sonographic findings need no further investigation. Sonography may
      therefore be very useful in hospitals around the world, where MRI may not be
      readily affordable or available.

PMID- 19854959
TI  - Ultrasound guidance versus electrical stimulation for femoral perineural catheter
      insertion.
AB  - OBJECTIVE: Continuous femoral nerve blocks provide potent analgesia and other
      benefits after knee surgery. Perineural catheter placement techniques using
      ultrasound guidance and electrical stimulation (ES) have been described, but the
      optimal method remains undetermined. We tested the hypothesis that ultrasound
      guidance alone requires less time for femoral perineural catheter insertion and
      produces equivalent results compared with ES alone. METHODS: Preoperatively,
      patients receiving a femoral perineural catheter for knee surgery were randomly
      assigned to either ultrasound guidance with a nonstimulating catheter or ES with
      a stimulating catheter. The primary outcome was the catheter placement procedure
      time (minutes) starting when the ultrasound transducer (ultrasound group) or
      catheter insertion needle (ES group) first touched the patient and ending when
      the catheter insertion needle was removed after catheter insertion. RESULTS:
      Perineural catheters placed with ultrasound guidance (n = 20) took a median (10th
      90th percentiles) of 5.0 (3.9-10.0) minutes compared with 8.5 (4.8-30.0) minutes
      for ES (n = 20; P = .012). All ultrasound-guided catheters were placed according
      to the protocol (n = 20) versus 85% of ES-guided catheters (n = 20; P = .086).
      Patients in the ultrasound group had a median procedure-related discomfort score
      of 0.5 (0.0-3.1) compared with 2.5 (0.0-7.6) for the ES group (P = .015). There
      were no vascular punctures with ultrasound guidance versus 4 in the ES group (P =
      .039). CONCLUSIONS: Placement of femoral perineural catheters takes less time
      with ultrasound guidance compared with ES. In addition, ultrasound guidance
      produces less procedure-related pain and prevents inadvertent vascular puncture.

PMID- 19854960
TI  - Feasibility of sonography for intra-articular injections in the knee through a
      medial patellar portal.
AB  - OBJECTIVE: The purpose of this study was to investigate the feasibility of using
      real-time high-resolution sonography to guide an injection needle into the intra
      articular space within the knee. METHODS: Eighty-nine patients with
      radiographically confirmed knee osteoarthritis (Kellgren-Lawrence grade 2 or 3)
      without an effusion were included. After sonographically guided or blind
      injection of hyaluronic acid (HA) and contrast dye through a medial patellar
      portal (MPP) into the knee joint, a radiographic image was made to ascertain
      whether the injected material had reached the intra-articular space. RESULT:
      Sonographically guided injections of HA into the knee joint had a significantly
      greater accuracy rate (95.6%) than blind injections (77.3%; P = .01).
      CONCLUSIONS: Intra-articular injections via an MPP using sonographic guidance may
      raise the accuracy rate in knee joint injections.

PMID- 19854961
TI  - Changes in cerebral and visceral blood flow velocities in asphyxiated term
      neonates with hypoxic-ischemic encephalopathy.
AB  - OBJECTIVE: The purpose of this study was to evaluate changes in the Doppler blood
      flow velocity (BFV) in the cerebral and visceral arteries in asphyxiated term
      neonates. METHODS: The BFV was measured in 47 asphyxiated and 37 healthy term
      neonates in the anterior cerebral artery, middle cerebral artery, basilar artery,
      internal carotid artery, celiac artery (CA), superior mesenteric artery (SMA),
      and renal artery (RA) up to the age of 60 to 149 days. RESULTS: At the age of 12
      to 120 hours after asphyxia, the mean BFV had increased, and the resistive index
      (RI) had decreased (P < .05) in all cerebral arteries in neonates with severe
      hypoxic-ischemic encephalopathy (HIE) compared with the control group. In
      neonates with severe HIE, the mean BFV in the RA had significantly decreased at
      the age of 3 to 240 hours, and the RI had increased at the age of 24 to 240
      hours, normalizing by the age of 21 to 59 days compared with the control group (P
      < .05). In the SMA, a decreased mean BFV was found in neonates with severe HIE
      compared with those with mild to moderate HIE only at the age of 24 to 36 hours.
      In neonates with mild to moderate HIE, the mean BFV had increased in the SMA and
      CA compared with the control group at the age of 2 to 11.9 hours. CONCLUSIONS: A
      severe alteration of the cerebral and visceral BFV takes place during the first
      days after asphyxia in neonates with different severities of HIE.

PMID- 19854962
TI  - Sonographic diagnosis of congenital variations of the extracranial vertebral
      artery and assessment of its circulation.
AB  - OBJECTIVE: The purpose of this study was to assess the value of sonographic
      examination of congenital variations of the extracranial vertebral artery
      associated with posterior circulation ischemia in children. METHODS: Sonography
      was performed on the vertebral arteries of 82 patients aged 2.5 to 14 years with
      a history of headache, vertigo, and syncope. An additional 86 unaffected children
      aged 2 to 14 years were included as a control group. Indices such as the
      diameter, passage, and morphologic characteristics of the vertebral artery were
      measured, as well as the arterial volume. The median values of these parameters
      were used for comparisons. RESULTS: A comparison between the control and 5 case
      groups showed that the bilateral diameter and volume in these 6 groups had
      significant variations (P < .05). A narrow diameter and abnormal passage of the
      vertebral artery resulted in reduced blood flow and an inadequate blood supply in
      the posterior circulation. There were 42 cases found to have congenital
      variations of the extracranial vertebral artery, 12 cases of congenital
      asymmetry, 15 cases of tortuosity, 5 cases of bilateral congenital asymmetry with
      tortuosity, 6 cases of congenital hypoplasticity, and 4 cases of an abnormal
      path. CONCLUSIONS: Certain children with a history of recurrent signs of vertigo,
      headache, and syncope were found to be afflicted with congenital variations of
      the extracranial vertebral artery. Sonography not only revealed the morphologic
      variations of the extracranial vertebral artery but also allowed an assessment of
      changes in blood flow such that posterior circulation ischemia could be
      determined.

PMID- 19854963
TI  - Interhemispheric comparisons of cerebral blood flow velocity changes during
      mental tasks with transcranial Doppler sonography.
AB  - OBJECTIVE: The purpose of this study was to evaluate hemispheric asymmetry of
      cerebral blood flow changes during various mental tests by applying transcranial
      Doppler sonography (TCD) to simultaneously monitor bilateral cerebral blood flow
      velocity changes. METHODS: Twenty-one participants without cerebrovascular
      disease performed 3 left hemispheric tasks (reading, calculation, and color
      scaling) and 3 right hemispheric tasks (face recognition, space imagination, and
      line orientation). RESULTS: Mean velocities of the rest and performing periods
      did not differ significantly between the left and right hemispheric tasks.
      Although greater acceleration of blood flow velocity was observed on the left
      than on the right in most of the 6 tasks except line orientation (mean left -
      right ratio difference [D(l-r)] ranged from -0.018 to 0.071), this difference was
      larger for left hemispheric tasks (mean D(l-r) ranged from 0.050 to 0.071) than
      right hemispheric tasks (mean D(l-r) ranged from -0.018 to 0.034; P < .001).
      Further comparisons of each pair of (ie, left and right) hemispheric tasks
      revealed that the most suitable left and right hemispheric tasks to show
      hemispheric asymmetry were reading and line orientation, respectively (P < .001).
      CONCLUSIONS: Hemispheric asymmetry of cerebral blood flow changes during mental
      tests is demonstrable with TCD only when comparing the D(l-r) in response to
      suitable paired left and right hemispheric tasks.

PMID- 19854964
TI  - Patients with Alzheimer disease have altered transmitral flow: echocardiographic
      analysis of the vortex formation time.
AB  - OBJECTIVE: There is considerable epidemiologic evidence that Alzheimer disease
      (AD) is linked to cardiovascular risk factors and associated with an increased
      risk of symptomatic left ventricular (LV) dysfunction. Formation of a vortex
      alongside a diastolic jet signifies an efficient blood transport mechanism. The
      vortex formation time (VFT) is an index of optimal conditions for vortex
      formation. We hypothesized that AD and its associated cardiovascular risk factors
      impair diastolic transmitral flow efficiency and, therefore, shift the VFT value
      out of its optimal range. METHODS: Echocardiographic studies were performed on 45
      participants in total: 22 patients with AD diagnosed according to the American
      Psychiatric Association's criteria and 23 age-matched individuals as a control
      group with cognitive function within normal limits. RESULTS: The
      echocardiographic ratio of the early to atrial phases of the LV filling
      velocities was significantly lower in the AD group (mean +/- SD, 0.67 +/- 14)
      when compared with the control individuals (0.79 +/- 0.14; P = .003). The
      interventricular septum diastolic thickness, left ventricular posterior wall
      diastolic thickness, and right ventricular end-diastolic diameter were
      significantly higher in the AD group (P <or= 0.04). The mitral annular diameters
      in the control and AD groups were nearly identical (P = .725). The time-velocity
      integral of the E wave had a lower value in the AD group than in the control
      group (P = .05), whereas the VFT was significantly lower in the AD group (P =
      .018). CONCLUSIONS: Our study suggests that patients with AD have impaired
      transmitral flow efficiency of diastolic filling, as measured by the VFT,
      compared with age-matched control individuals.

PMID- 19854965
TI  - Focused ultrasound microbubble destruction-mediated changes in blood-brain
      barrier permeability assessed by contrast-enhanced magnetic resonance imaging.
AB  - OBJECTIVE: The purpose of this study was to use enhanced magnetic resonance
      imaging (MRI) to evaluate the changes of blood-brain barrier (BBB) permeability
      in target and nontarget areas of rabbit brains after BBB disruption induced by
      focused ultrasound-mediated microbubble destruction. METHODS: Focused ultrasound
      (1.1 MHz) in combination with a sulfur hexafluoride microbubble contrast agent
      was applied at 2 or 3 target locations in 1 hemisphere of 29 rabbit brains to
      induce BBB disruption. The opposite side was used as a control, and a normal
      group contained another 14 rabbits that did not undergo sonication. The MRI
      signal intensity enhancement in the target locations was detected to evaluate
      gadolinium (Ga) retention after sonication, and extravasation of Evans blue (EB)
      dye was detected to evaluate the BBB disruption quantitatively at different times
      after sonication (0.5, 2, 4, 6, 8, and 24 hours and 1 week). RESULTS: Compared
      with the control group, Ga retention, changes in EB content, and extravasation in
      the cerebral cortex of the sonicated group peaked at 2 hours (P < .01) and
      decreased to the normal level 8 hours after sonication (P < .01). There was no
      visual evidence of injury or hemorrhage within the brain parenchyma of all of the
      rabbits' treated hemispheres. CONCLUSIONS: Magnetic resonance imaging-guided
      focused ultrasound can disrupt the BBB reversibly and can allow targeted delivery
      of some molecules that normally cannot cross the BBB to locations in the brain.
      Changes in BBB permeability develop within minutes after sonication as a result
      of a combination of factors. The BBB has a self-repairing characteristic, which
      is activated after ultrasound sonication. This may offer an improvement in future
      clinical applications for central nervous system diseases.

PMID- 19854966
TI  - Accuracy of volumetric flow rate measurements: an in vitro study using modern
      ultrasound scanners.
AB  - OBJECTIVE: Volumetric flow measurement with Doppler ultrasound is useful in
      assessing blood flow as part of an evaluation of arteriovenous fistula maturity
      in patients undergoing hemodialysis. In this study, we assessed both accuracy and
      variability in volumetric flow measurements obtained using modern and
      commercially available ultrasound systems and an in vitro experimental setup.
      METHODS: Volumetric flow measurements using duplex ultrasound were obtained by 3
      users operating 5 different systems for randomized flow in the range of 100 to
      1000 mL/min. Users performed 3 consecutive measurements at a given flow rate.
      Data were analyzed using statistical techniques to assess measurement accuracy
      and variability. RESULTS: Over the span of flow rates studied, the root mean
      square error (RMSE) for the 5 ultrasound systems ranged from 38.8 to 79.7, 36.8
      to 52.0, 73.0 to 85.3, 26.7 to 44.6, and 43.9 to 93.5 mL/min. Corresponding
      average RMSE values were 60.3, 42.7, 81.1, 37.2, and 64.4 mL/min, respectively. A
      linear regression analysis of mean interobserver measurements revealed an
      excellent correlation for all ultrasound systems (r(2) > 99.1%). Assessment of
      intraobserver measurements revealed no statistically significant differences for
      any ultrasound system evaluated (P > .94). Comparison of interobserver
      measurements indicates no statistically significant differences between any of
      the 5 systems (P > .14). CONCLUSIONS: Modern ultrasound systems are reasonably
      accurate in blood flow measurement in an experimental setup mimicking clinically
      relevant blood flow ranges in a hemodialysis fistula. Users need adequate
      training and experience to perform multiple measurements and use appropriate
      techniques to minimize errors in flow measurement.

PMID- 19854967
TI  - Cardiac arrhythmia and injury induced in rats by burst and pulsed mode ultrasound
      with a gas body contrast agent.
AB  - OBJECTIVE: Premature complexes (PCs) in the electrocardiogram (ECG) signal have
      been reported for myocardial contrast echocardiography and also for burst mode
      (physical therapy) ultrasound with gas body contrast agents at lower peak
      rarefactional pressure amplitudes (PRPAs). For contrast echocardiography,
      irreversibly injured cardiomyocytes have been associated with the arrhythmia. The
      objective was to determine whether cardiomyocyte injury is associated with the
      PCs induced by the burst mode at lower PRPAs. METHODS: Anesthetized rats were
      exposed to focused 1.5-MHz ultrasound in a water bath. Evans blue dye was
      injected intraperitoneally to stain injured cardiomyocytes, and a perflutren
      lipid microsphere ultrasound contrast agent was infused intravenously. The
      continuous burst mode simulated physical therapy ultrasound. Intermittent 2
      millisecond bursts, or envelopes of pulses simulating diagnostic ultrasound, were
      triggered 1:4 at end systole. Premature complexes were observed on ECG
      recordings, and stained cardiomyocytes were counted in frozen sections. RESULTS:
      The continuous burst mode produced variable PCs and stained cells above a 0.3-MPa
      PRPA. The triggered bursts above 0.3 MPa and pulse envelopes above 1.2 MPa
      produced statistically significant (P < .01) PCs and stained cardiomyocytes.
      CONCLUSIONS: Irreversible cardiomyocyte injury was associated with the
      development of PCs for the burst mode and occurred at substantially lower PRPAs
      than for pulsed ultrasound.

PMID- 19854968
TI  - Wideband high-frequency echocardiography to evaluate myocardial infarct size.
AB  - OBJECTIVE: This study was designed to validate the feasibility of wideband high
      frequency ultrasound imaging to resolve in vivo the degree, location, and
      morphologic changes of myocardial infarction (MI) in a rat model. METHODS: The
      left anterior descending coronary artery was ligated in the test group (n = 41),
      and the sham control group did not have ligation (n = 7). The rats were examined
      with 10- to 22-MHz echocardiography to evaluate the MI size, location, and
      geometric formation. RESULTS: The endocardial chamber shape was deformed, with
      enlargement of the anteroposterior dimension and fractional shortening, and was
      comparable with the degree of MI both in short- and long-axis sections of the
      left ventricle. Histologic analysis showed remodeling to different extents
      corresponding to different MI sizes (small, medium, and large). CONCLUSIONS: The
      results suggest that this technique can be used in vivo to evaluate the MI
      location, size, and morphologic changes corresponding to the extent of the
      injury.

PMID- 19854969
TI  - Optimized noninvasive monitoring of thermal changes on digital B-mode renal
      sonography during revascularization therapy.
AB  - OBJECTIVE: Noninvasive real-time thermal change monitoring of human internal
      organs can play a critical role in diagnosis and treatment of many disorders,
      including reperfusion of renal arteries during anticoagulation therapy. METHODS:
      This article focuses on tissue temperature detection using ultrasound velocity
      changes in different structures and their related speckle shift from their
      primary locations on high-quality B-mode digital sonography. We evaluated
      different speckle-tracking techniques and optimized them using appropriate motion
      estimation methods to determine the best algorithm and parameters. RESULTS:
      Performing thermal detection methods on simulated phantoms showed a good
      correlation between speckle shifts and the ground truth temperature. For the
      simulated images, average thermal error was 0.5 degrees C with an SD of 0.5
      degrees C, where lower errors can be obtained in noiseless (motionless) data. The
      proposed technique was evaluated on real in vivo cases during surgical occlusion
      and reopening of the renal segmental artery and showed the potential of the
      algorithm for observation of internal organ changes using only digital ultrasound
      systems for diagnosis and therapy. CONCLUSIONS: The adaptive Rood pattern search
      proved to be the best block-matching technique, whereas the multiresolution Horn
      Schunck technique was the best gradient optical flow method. The extracted
      thermal change during in vivo revascularization therapy is promising. In
      addition, we present an evaluation of several block-matching and optical flow
      motion estimation techniques.

PMID- 19854970
TI  - Accuracy of sonographically guided posterior subtalar joint injections:
      comparison of 3 techniques.
AB  - OBJECTIVE: The primary purpose of this investigation was to determine the
      accuracy of 3 different sonographically guided posterior subtalar joint (PSTJ)
      injection techniques in an unembalmed cadaveric model. METHODS: A single
      experienced examiner injected the PSTJs of 12 unembalmed cadaveric ankle-foot
      specimens using the anterolateral, posterolateral, and posteromedial approaches.
      The injection order for each specimen was randomized, and each technique was
      completed with a different-color diluted latex solution. Coinvestigators blinded
      to the injection technique dissected each specimen and graded the colored latex
      location as accurate (in the PSTJ), accurate with overflow (within the PSTJ but
      also in other regions), or inaccurate (no latex in the joint). RESULTS: All 3
      sonographically guided PSTJ injection approaches accurately placed latex into the
      PSTJ (100% accuracy). Latex was also found in adjacent regions in 19.4% (7 of 36)
      of injections: 8.3% (3 of 36) within the tibiotalar joint, 8.3% (3 of 36) in the
      peroneal (fibularis) tendon sheath, and 2.8% (1 of 36) in the flexor hallucis
      longus tendon sheath. The anterolateral approach placed latex outside the PSTJ
      25% of the time (3 of 12 injections: 1 tibiotalar and 2 peroneal [fibularis]
      sheath), the posterolateral approach 25% of the time (3 of 12 injections: 1
      tibiotalar, 1 peroneal [fibularis] sheath, and 1 flexor hallucis longus tendon
      sheath), and the posteromedial approach 8.3% of the time (1 tibiotalar).
      CONCLUSIONS: This cadaveric investigation suggests that all 3 sonographically
      guided PSTJ techniques may be used to access the PSTJ with a high degree of
      accuracy. Clinicians should consider sonographically guided PSTJ injections as a
      favorable alternative to fluoroscopy and computed tomographic guidance when
      diagnostic or therapeutic image-guided PSTJ injections are indicated.

PMID- 19854971
TI  - Image registration accuracy of a 3-dimensional transrectal ultrasound-guided
      prostate biopsy system.
AB  - OBJECTIVE: For a follow-up prostate biopsy procedure, it is useful to know the
      previous biopsy locations in anatomic relation to the current transrectal
      ultrasound (TRUS) scan. The goal of this study was to validate the performance of
      a 3-dimensional TRUS-guided prostate biopsy system that can accurately relocate
      previous biopsy sites. METHODS: To correlate biopsy locations from a sequence of
      visits by a patient, the prostate surface data obtained from a previous visit
      needs to be registered to the follow-up visits. Two interpolation methods, thin
      plate spline (TPS) and elastic warping (EW), were tested for registration of the
      TRUS prostate image to follow-up scans. We validated our biopsy system using a
      custom-built phantom. Beads were embedded inside the phantom and were located in
      each TRUS scan. We recorded the locations of the beads before and after pressures
      were applied to the phantom and then compared them with computer-estimated
      positions to measure performance. RESULTS: In our experiments, before system
      processing, the mean target registration error (TRE) +/- SD was 6.4 +/- 4.5 mm
      (range, 3-13 mm). After registration and TPS interpolation, the TRE was 5.0 +/-
      1.03 mm (range, 2-8 mm). After registration and EW interpolation, the TRE was 2.7
      +/- 0.99 mm (range, 1-4 mm). Elastic warping was significantly better than the
      TPS in most cases (P < .0011). For clinical applications, EW can be implemented
      on a graphics processing unit with an execution time of less than 2.5 seconds.
      CONCLUSIONS: Elastic warping interpolation yields more accurate results than the
      TPS for registration of TRUS prostate images. Experimental results indicate
      potential for clinical application of this method.

PMID- 19854972
TI  - High-frequency sonography in the evaluation of psoriasis: nail and skin
      involvement.
AB  - OBJECTIVE: The purpose of this study was to show the potential of the latest
      sonographic equipment using high-frequency probes and a very sensitive power
      Doppler (PD) technique in depicting both skin and nail changes in patients
      affected by psoriasis. METHODS: The study was conducted in 30 patients with a
      diagnosis of psoriasis clinically performed by an experienced dermatologist and
      15 healthy participants, using a currently available sonography system equipped
      with a variable-frequency transducer ranging from 6 to 18 MHz and a Doppler
      frequency ranging from 7 to 14 MHz. RESULTS: The images illustrated in this
      presentation are representative examples of the ability of sonography to show and
      characterize even minimal morphostructural and blood flow changes in patients
      with both psoriatic plaques and onychopathy. CONCLUSIONS: This report provides
      pictorial evidence that high-resolution gray scale sonography with a PD technique
      is a real-time and noninvasive imaging technique that can be used as an adjunct
      to the clinical evaluation in assessing psoriatic disease.

PMID- 19854973
TI  - Duodenal and rectal hematomas complicating endoscopic biopsy: use of sonography
      in pediatrics.
AB  - OBJECTIVE: Intramural duodenal hematomas (IDHs) after nontherapeutic endoscopic
      biopsy are rare. Rectal hematomas (RHs) have not been reported previously. A
      review of the literature revealed 18 cases of IDHs. METHODS: We reviewed 3 cases
      that occurred within a 4-month period at our institution. RESULTS: We report a
      series of 3 cases occurring within a 4-month period. In addition, we report a
      concurrent RH in 1 of these cases. After becoming symptomatic, 2 of these
      patients had a diagnosis by computed tomography, the third by sonography. All
      patients had conservative management and were followed with sonography.
      CONCLUSIONS: Sonography was found to be an accurate, safe, and nonionizing way to
      diagnose and follow hematomas in pediatric patients.

PMID- 19854974
TI  - Eggshell calcification of the testis: ultrasonographic findings.

PMID- 19854975
TI  - Myxoma of the left ventricular outflow tract.

PMID- 19854976
TI  - Isolated double-orifice mitral valve anomaly on 3-dimensional transesophageal
      echocardiography.

PMID- 19854977
TI  - Maintenance of normal radiocephalic fistula flow via the ulnar artery in a
      patient with occlusion of the radial artery.

PMID- 19854978
TI  - Sonographic detection of acetabular polyethylene liner dissociation in total hip
      arthroplasty.

PMID- 19854979
TI  - Pneumothorax diagnosis by extended focused assessment with sonography for trauma.

PMID- 19854984
TI  - Effects of ruminal protein degradability and frequency of supplementation on
      nitrogen retention, apparent digestibility, and nutrient flux across visceral
      tissues in lambs fed low-quality forage.
AB  - Two experiments were conducted to determine the effect of ruminal protein
      degradability and supplementation frequency on intake, apparent digestibility, N
      retention, and nutrient flux across visceral tissues of lambs fed a low-quality
      forage diet. In both experiments, wethers were fed a basal diet of mature crested
      wheatgrass hay (4.2% CP) for ad libitum consumption plus 1 of 4 supplements: 1) a
      high RDP supplement provided daily (RDP-D), 2) the high RDP supplement provided
      on alternate days (RDP-A), 3) a high RUP provided on alternate days (RUP-A), or
      4) a 50:50 mixture of the RDP and RUP supplements provided on alternate days. In
      Exp. 1, 12 lambs (29.9 +/- 2.7 kg initial BW) were used. Forage OM, NDF, and ADF
      intake were not affected by treatment. Total tract digestibilities (OM, NDF, ADF,
      and N) were unaffected (P >or= 0.15) by treatment. Neither protein degradability
      nor supplementation frequency had an effect (P >or= 0.52) on N retention. In Exp.
      2, 15 lambs (34 +/- 4 kg initial BW) fitted with indwelling catheters in a
      hepatic vein, the hepatic portal vein, a mesenteric vein, and a mesenteric artery
      were used. Release of ammonia N by the portal-drained viscera (PDV) was reduced
      (P = 0.004) in alternate-day-supplemented lambs compared with RDP-D.
      Consequently, hepatic uptake of ammonia N was least (P = 0.003) in all alternate
      day lambs. Alpha-amino nitrogen (AAN) release by the PDV and hepatic uptake of
      AAN were not affected by treatment or supplementation frequency. Additionally,
      hepatic output and PDV uptake of urea N were not affected by treatment. Hepatic N
      uptake (ammonia N + AAN) accounted for urea synthesized by the liver in all
      treatments; however, hepatic urea synthesis was approximately 4.5-fold less for
      RUP-A lambs. This suggests that the provision of AA as RUP may provide a delay in
      ureagenesis, thus altering the timing of N recycling.

PMID- 19854985
TI  - Effects of ruminal protein degradability and frequency of supplementation on site
      and extent of digestion and ruminal fermentation characteristics in lambs fed low
      quality forage.
AB  - Four ruminally and duodenally cannulated Suffolk wether lambs (34.5 +/- 2.0 kg
      initial BW) were used in a 4 x 4 Latin square-designed experiment to examine the
      effects of ruminal protein degradability and supplementation frequency on site
      and extent of digestion in lambs consuming a low-quality forage diet. Wethers
      were fed a basal diet of mature crested wheatgrass hay (4.2% CP) for ad libitum
      consumption plus 1 of 4 supplements: 1) a high RDP supplement provided daily (RDP
      D), 2) the high RDP supplement provided on alternate days (RDP-A), 3) a high RUP
      supplement provided on alternate days (RUP-A), or 4) a 50:50 mixture of the RDP
      and RUP supplements, provided on alternate days (MIX-A). Forage OM, N, NDF, or
      ADF intakes were not affected by treatment. True ruminal OM digestibility was
      greater (P < 0.001) for MIX-A lambs compared with other treatments. True ruminal
      N digestibility was less (P < 0.01) in RUP-A lambs compared with other
      treatments. Ruminal digestibilities of NDF and ADF were greater (P <or= 0.01) for
      MIX-A lambs compared with other treatments. There was a treatment x hour
      interaction (P < 0.001) with a delay in peak concentrations within the RDP-A
      lambs. However, lambs supplemented with RUP had less (P < 0.001) ruminal ammonia
      concentrations compared with RDP-D lambs, with RUP-A lambs exhibiting the least
      concentrations and least variation over time. Ruminal urease activity was not
      affected by treatment. Microbial N flow was not affected by treatment; however,
      there was an increase (P = 0.004) in microbial efficiency for RDP-D lambs.
      Alternate day protein supplementation with a mixture of RDP and RUP may improve
      digestibility in lambs consuming low-quality forage, which may be related to
      decreased fluctuation in ruminal ammonia concentrations as a result of greater
      endogenous N recycling.

PMID- 19854986
TI  - Effect of dietary protein and lysine fluctuations in the absence and presence of
      ractopamine on performance and carcass quality of late-finishing pigs.
AB  - Two experiments with finishing pigs were conducted to evaluate the effects of
      fluctuating dietary CP levels and ractopamine on performance and carcass traits.
      In Exp. 1, a total of 408 finishing pigs (mixed sex) were assigned to 1 of 4
      protein regimens. Average initial and final BW were 89 and 123 kg, respectively.
      Pigs on treatments 1 to 4 were fed 16, 11, 16, and 13% CP from wk 0 to 2,
      respectively. From wk 2 to 5, the pigs on regimens 1 to 4 were then fed 15,
      18.33, 18, and 20% CP, respectively, with regimens 3 and 4 also containing
      supplemental ractopamine (9.9 mg/kg) from wk 2 to 5. Overall (wk 0 to 5), BW
      gain, G:F, loin depth, percentage of lean, and dressing percentage were improved
      (P < 0.05) in pigs on regimens 3 and 4 compared with those on regimens 1 and 2.
      No statistically significant overall (wk 0 to 5) protein sequence regimen
      differences occurred between the standard regimens (1 and 3) and the low-high CP
      regimens (2 and 4). Experiment 2 involved 172 finishing pigs (mixed sex) in 2
      protein regimens. Average initial and final BW were 91 and 136 kg, respectively.
      The diets consisted of 1) a control (16% CP from d 0 to 14, 18% CP + 4.95 mg of
      ractopamine/kg from d 14 to 24, and 18% CP + 9.9 mg of ractopamine/kg from d 24
      to 35; 2) a low-high CP regimen (12.5% CP from d 0 to 14, 20.33% CP + 4.95 mg of
      ractopamine/kg from d 14 to 24, and 20.33% CP + 9.9 mg of ractopamine/kg from d
      24 to 35. From d 0 to 14, pigs fed the low CP diet (12.5% CP) had reduced (P <
      0.05) BW gain and G:F compared with those fed the control diet (16% CP). In
      contrast, from d 14 to 35, pigs on the low-high regimen had improved (P < 0.08)
      BW gain and G:F compared with pigs on the control regimen. Despite the wide
      dietary CP fluctuations for pigs in Exp. 2, performance and carcass traits were
      similar for both regimens over the 35-d test period. These data indicate that
      pigs fed deficient levels of CP and Lys for 14 d, followed by increased levels of
      CP and Lys during a subsequent 21-d period can recover and achieve growth
      performance and carcass merit equal to that achieved with a conventional protein
      feeding regimen.

PMID- 19854988
TI  - Evidence for parent-of-origin effects on genetic variability of beef traits.
AB  - Imprinted genes are involved in many aspects of development in mammals, plants,
      and perhaps birds and may play a role in growth and carcass composition of
      slaughter animals. In the presence of genomic imprinting the expression and,
      consequently, the effect on the phenotype of maternal and paternal alleles are
      different. For genetic evaluation genomic imprinting can be accounted for by
      incorporating 2 additive genetic effects per animal; the first corresponds to a
      paternal and the second to a maternal expression pattern of imprinted genes. This
      model holds whatever the mode of imprinting may be: paternal or maternal, full or
      partial, or any combination thereof. A set of slaughter data from 65,233 German
      Simmental fattening bulls was analyzed with respect to the relative importance of
      the genetic imprinting variance. Besides slaughter weight, net daily BW gain, and
      killing out percentage, there were 22 other traits describing the carcass
      composition. The latter traits were evaluated by automatic video-imaging devices
      and were composed of weights of valuable cuts as well as fat and meatiness grade.
      The number of ancestors in the pedigree was 356,880. Genomic imprinting
      significantly contributed to the genetic variance of 10 traits, with estimated
      proportions between 8 and 25% of the total additive genetic variance. For 6 of
      these traits, the maternal contribution to the imprinting variance was larger
      than the paternal, whereas for all other traits the reverse was true. Fat grade
      only showed a paternal contribution to the imprinting variance. Estimates of
      animal model heritabilities of automatic video-imaging-recorded carcass traits
      ranged between 20 and 30%.

PMID- 19854987
TI  - Impacts of amino acid nutrition on pregnancy outcome in pigs: mechanisms and
      implications for swine production.
AB  - Pigs suffer up to 50% embryonic and fetal loss during gestation and exhibit the
      most severe naturally occurring intrauterine growth retardation among livestock
      species. Placental insufficiency is a major factor contributing to suboptimal
      reproductive performance and reduced birth weights of pigs. Enhancement of
      placental growth and function through nutritional management offers an effective
      solution to improving embryonic and fetal survival and growth. We discovered an
      unusual abundance of the arginine family of AA in porcine allantoic fluid (a
      reservoir of nutrients) during early gestation, when placental growth is most
      rapid. Arginine is metabolized to ornithine, proline, and nitric oxide, and these
      compounds possess a plethora of physiological functions. Nitric oxide is a
      vasodilator and angiogenic factor, whereas both ornithine and proline are
      substrates for placental synthesis of polyamines, which are key regulators of
      protein synthesis and angiogenesis. Additionally, arginine, leucine, glutamine,
      and proline activate the mammalian target of rapamycin cell-signaling pathway to
      enhance protein synthesis and cell proliferation in placentae. To translate basic
      research on AA biochemistry and nutrition into application, dietary
      supplementation with 0.83% l-arginine to gilts on d 14 to 28 or d 30 to 114 of
      gestation increased the number and litter birth weight of live-born piglets. In
      addition, supplementing the gestation diet with 0.4% l-arginine plus 0.6% l
      glutamine enhanced the efficiency of nutrient utilization, reduced variation in
      piglet birth weight, and increased litter birth weight. By regulating syntheses
      of nitric oxide, polyamines, and proteins, functional AA stimulate placental
      growth and the transfer of nutrients from mother to embryo or fetus to promote
      conceptus survival, growth, and development.

PMID- 19854989
TI  - A mechanistic model for predicting intake of forage diets by ruminants.
AB  - Accurate voluntary feed intake (VFI) prediction is critical to the productivity
      and profitability of ruminant livestock production systems. Simple empirical
      models have been used to predict VFI for decades, but they are inflexible,
      restrictive, and poorly accommodate many feeding conditions, such as those of
      developing countries. We have developed a mechanistic model to predict VFI over a
      range of forage diets (low- and high-quality grasses and legumes) by wild and
      domestic ruminants of varying physiological states (growth, lactation, gestation,
      nonproductive). Based on chemical reactor theory, the model represents the
      reticulorumen, large intestine, and blood plasma as continuous stirred-tank
      reactors and the small intestine as a plug flow reactor. Predicted VFI is that
      which 1) fulfills an empirical relationship between chemostatic and distention
      feedback observed in the literature, and 2) leads to steady-state conditions.
      Agreement between observed and actual VFI was great (generally R(2) >0.9, root
      mean square prediction error <1.4 kg/d, CV <25%). Root mean square prediction
      error for our model was only 67% that of the Beef NRC (2000) model, the leading
      empirical prediction system for cattle. Together, these results demonstrate that
      our model can predict ruminant VFI more broadly and accurately than prior methods
      and, by consequence, serve as a crucial tool to ruminant livestock production
      systems.

PMID- 19854990
TI  - Dose response to cinnamaldehyde supplementation in growing beef heifers: ruminal
      and intestinal digestion.
AB  - The objective of this study was to determine if cinnamaldehyde (CIN) could be
      used to improve feed intake, digestion, and immune status in growing beef heifers
      fed high-concentrate diets. The experiment was designed as a 4 x 4 Latin square
      using 4 ruminally and duodenally cannulated beef heifers with 4 treatments:
      control (no CIN added), 400 mg/d of CIN (low), 800 mg/d of CIN (medium), and
      1,600 mg/d of CIN (high), and four 21-d periods. Feed intake, rumen pH and
      fermentation characteristics, site and extent of digestion, microbial N
      synthesis, blood metabolites, and acute phase protein response were measured. The
      diets consisted of 15% barley silage, 80% dry-rolled barley grain, and 5%
      supplement (DM basis). Intakes (kg/d) of DM, OM, NDF, starch, and N were
      quadratically (P = 0.04) changed with increasing CIN supplementation. The amount
      of OM fermented in the rumen quadratically (P = 0.02) decreased with increasing
      CIN. Digestibilities (% of intake) of OM, NDF, and N in the rumen were not
      affected by supplementing with low and medium CIN, but they were reduced by 8% (P
      = 0.10), 31% (P = 0.05), and 17% (P = 0.05), respectively, with high CIN.
      Similarly, digestibilities of OM and NDF in the total tract also tended to be
      reduced by 7% (P = 0.10) and 20% (P = 0.10), respectively, with high CIN because
      supplementation of CIN had minimal effects on intestinal digestibility. Flows
      (g/d) of microbial N and other nutrients to the duodenum were not affected by CIN
      supplementation, even though the amount of ruminal fermented OM varied with level
      of CIN supplementation. Rumen pH, total VFA concentration, and molar proportions
      of individual VFA were not affected by CIN. Although concentrations of NEFA (P =
      0.06) and triglyceride (P = 0.01) were quadratically changed with increasing CIN
      supplementation, blood concentrations of glucose and urea N, white blood cell
      counts, serum amyloid A, and lipopolysaccharide in plasma were not affected by
      CIN. Plasma haptoglobin numerically (P = 0.11) decreased with the medium dose of
      CIN fed compared with control. The results indicate that supplementation of a
      high-concentrate diet with a low dose of CIN resulted in small increases in
      nutrient availability in the rumen due to increased feed intake and greater
      ruminal digestion of OM. However, feed intake and ruminal digestion of feeds were
      adversely affected when a high dose of CIN was used.

PMID- 19854991
TI  - Pain mitigation after band castration of beef calves and its effects on
      performance, behavior, Escherichia coli, and salivary cortisol.
AB  - Eighty-nine steer and bull calves (210 +/- 20 d of age) were randomly assigned to
      a 2 x 2 factorial arrangement of treatments to study the effect of sham or band
      castration (CAST) with or without pain medication (MED) on performance, behavior,
      cortisol, and Escherichia coli shedding. Steers (serving as controls; C) were
      previously castrated at 34 +/- 10 d of age, whereas bulls (B) remained intact
      until band application on d 20 of the experiment. One-half of the calves in each
      group received pain medication (M; xylazine epidural and intravenous flunixin
      meglumine) or saline (NM) solutions at 0.5 h before castration. Feed intake, ADG,
      and feeding behavior were measured over a 3-wk period before (used as covariates)
      and a 6-wk period after castration. Fecal and saliva samples were collected from
      32 calves for E. coli enumeration at -7 (covariate), 2, 5, and 7 d, and for
      cortisol concentration at -0.5 (covariate), 0, 0.5, 1, 2, 4, 24, 48, 168, and 336
      h relative to castration, respectively. Lying behavior was measured in the home
      pen and step length at exit from the chute. There were no significant CAST x MED
      interactions on growth rate or feed intake. Overall ADG was less in B compared
      with C (P < 0.001), but feed intake was less during wk 4 only (P = 0.01). On
      average, M had less intake (P = 0.02) and eating rate (P = 0.04) than NM calves.
      The BM had less fecal E. coli counts than CM (P = 0.05) and castrated and
      nonmedicated calves (P = 0.08). Salivary cortisol was less in BM compared with
      the rest of treatments at 1 and 2 h after banding (P <or= 0.05). Castration
      reduced time spent lying (P = 0.06) and step length (P = 0.01) until d 28 after
      banding, whereas M reduced lying and step length on day of banding only (P <or=
      0.06). Significant CAST x MED interactions were observed for frequency of visits
      to feeders and meal size, length, and frequency (P < 0.05) independent of the
      time after castration. This was due to greater values in the noncastrated and non
      pain-medicated group compared with the rest, except for reduced meal frequency,
      indicating that pain medication and castration both affected feeding behavior.
      The medication protocol used in the present study eliminated the acute cortisol
      surge, which may be linked to reduced fecal E. coli counts observed during wk 1
      after banding. However, feed intake, growth, and behavior suggested that pain was
      greatest during wk 3 and 4 after band application, which highlights the need for
      chronic pain mitigation strategies.

PMID- 19854993
TI  - Technical note: comparison of salivary and serum cortisol concentrations after
      adrenocorticotropic hormone challenge in ewes.
AB  - An ACTH challenge was conducted to determine if salivary cortisol concentration
      reflects serum cortisol concentration in ewes. Twelve yearling ewes (64.0 +/- 1.2
      kg) were administered ACTH (100 IU, intravenously) or saline. Serum and salivary
      samples were collected at 30-min intervals for 2 h before ACTH administration, at
      15-min intervals for 2 h after treatment, and at 30-min intervals for an
      additional 3 h, and cortisol concentration was determined by RIA. Although ewes
      responded to ACTH and saline, cortisol concentration was greater (P < 0.001) in
      ACTH-treated ewes from 15 to 120 min and tended to be greater (P = 0.054) at 150
      min after challenge in serum. In saliva, cortisol concentration was greater (P <
      0.001) in ACTH-treated ewes from 30 to 120 min and tended to be greater (P =
      0.092) at 15 min after challenge. No difference was observed between ACTH-treated
      ewes and controls for time to peak serum cortisol concentration (P = 0.126) and
      time to peak salivary cortisol concentration (P = 0.109), or between saliva and
      serum for time to peak cortisol concentration (P = 0.220) and return to baseline
      cortisol concentration (P = 0.341). The serum (P = 0.009) and salivary (P =
      0.050) cortisol areas under the curve between 0 and 150 min were greater for ACTH
      treated ewes than controls, and serum (P = 0.002) and salivary (P < 0.001)
      cortisol return to baseline concentration was longer for ACTH-treated ewes. The
      correlation coefficient between serum and salivary cortisol concentrations was
      0.88 (P < 0.001). These data indicate that salivary cortisol concentration is
      closely related to serum cortisol concentration and that the former may represent
      a suitable noninvasive alternative to blood collection for measurement of
      cortisol in sheep.

PMID- 19854992
TI  - Effects of twin pregnancy and dry period feeding strategy on milk production,
      energy balance, and metabolic profiles in dairy cows.
AB  - The present study evaluated the interaction of pregnancy type [PT; single (S) vs.
      twin (T)] and dry period feeding management [D; close-up (CU) diet (NE(l) = 1.54
      Mcal/kg of DM)] throughout the entire dry period (8W) vs. far-off (FO) diet
      (NE(l) = 1.32 Mcal/kg of DM) from 60 to 21 d before expected calving date (ECD)
      followed by CU diet until calving (3W). Treatments were arranged in a 2 x 2
      factorial with a randomized block design with primiparous (n = 8) and multiparous
      (n = 39) Holstein cows. We hypothesized that increasing the duration of feeding a
      CU diet would improve metabolic status and lactation performance for cows with T,
      but not for cows with S. All cows were fed similarly in late lactation (90 to 60
      d before ECD; diet NE(l) = 1.58 Mcal/kg of DM) and in early lactation (calving to
      105 DIM; diet NE(l) = 1.71 Mcal/kg of DM). Prepartum DMI as percentage of BW did
      not differ (P > 0.10) with D but tended to be greater (P = 0.10) for cows with S
      than with T. Cows with T tended to have greater (P = 0.08) BW than cows with S,
      but conceptus-free BW was less (P = 0.001) for cows with T than for cows with S.
      No differences (P > 0.10) were detected in prepartum BCS or BCS change with PT or
      D. Energy balance (EB) was greater for cows with S than with T (P < 0.001) and
      for cows fed 8W vs. 3W (P = 0.01). Cows with T had greater (P < 0.001) NEFA and a
      tendency for greater liver triglycerides (TG; P = 0.07) and plasma beta
      hydroxybutyrate (BHBA; P = 0.06) than cows with S. Prepartum cows fed 3W had
      greater (P = 0.01) liver TG and greater (P = 0.02) plasma NEFA, but less (P =
      0.02) plasma BHBA than cows fed 8W. Plasma glucose (P < 0.004) and liver glycogen
      (P = 0.02) were less for cows with T but were not affected (P > 0.10) by D.
      Postpartum, there was no effect (P > 0.1) of PT or D on mean DMI as percentage of
      BW, BW, and BCS, but there was an interaction (P = 0.02) of PT x D for mean BCS.
      Cows that calved T were in a more positive (P = 0.004) EB than cows that calved
      S. Milk production was 5.2 kg/d greater (P = 0.04) for cows fed 8W; however, they
      were in less (P = 0.01) EB than cows that received 3W. Postpartum cows that
      calved T had decreased concentrations of plasma NEFA (P = 0.02) and liver TG (P =
      0.04) but greater concentrations of plasma glucose (P = 0.03) than cows that
      calved S. Plasma BHBA (P = 0.07) and NEFA tended (P = 0.06) to be greater for
      cows that received 8W than 3W. Neither PT nor D affected (P > 0.1) plasma glucose
      and liver glycogen. There was a tendency for an interaction of PT x D for plasma
      NEFA and liver TG. In contrast to our hypothesis, response to D was independent
      of PT. Based on milk production data from the present experiment, 8W is a more
      desirable feeding strategy than 3W.

PMID- 19854994
TI  - Use of chitosans to modulate ruminal fermentation of a 50:50 forage-to
      concentrate diet in sheep.
AB  - The objective of this study was to investigate the effects of chitosan (CHI) on
      ruminal and cecal fermentation and on apparent digestibility in sheep. In a first
      trial, 4 ruminally fistulated sheep fed an alfalfa hay and concentrate diet
      formulated to meet 1.2 times their maintenance energy requirements were assigned
      to 2 treatments [no-additive control (CTR), or 136 mg/kg of BW of CHI] for 19 d
      in a 2 x 2 crossover design. Samples of ruminal fluid and feces were taken for
      VFA and NH(3)-N concentrations. At the end of each period of the crossover,
      ruminal fluid was used as inoculum for batch cultures (24 and 96 h), and the
      effects on rate and extent of gas production and on fermentation variables for
      starch, cellulose, and the same diet fed to the animals were calculated. In a
      second trial, 4 sheep fed the alfalfa hay and concentrate diet were assigned to 2
      treatments (CTR and CHI), as for the first trial, but this time for 14 d in a 2 x
      2 crossover design. Apparent digestibility was studied. In the first trial, in
      terms of ruminal fermentation, CHI did not affect (P = 0.12) total VFA
      concentration or acetate proportion, but increased propionate proportion (P =
      0.004) and propionate-to-acetate ratio (C3:C2; P = 0.007) and decreased branched
      chain VFA (BCVFA) proportion (P = 0.003) and NH(3)-N concentration (P = 0.045).
      In feces, CHI decreased total VFA concentration (P = 0.01) and acetate (P =
      0.045) and butyrate (P = 0.025) proportions, and increased propionate (P = 0.04),
      valerate (P = 0.01), and BCVFA (P = 0.032) proportions and C3:C2 ratio (P =
      0.045). In batch cultures, when starch was used as substrate, CHI decreased
      acetate proportion (P = 0.016) and methane production (P = 0.03) and increased
      propionate and valerate proportions and C3:C2 ratio (P < 0.001). When cellulose
      was used as substrate, CHI decreased in vitro OM digestibility (P = 0.033), total
      VFA concentration, propionate proportion (P < 0.001), C3:C2 ratio (P = 0.006),
      methane production (P < 0.001), NH(3)-N concentration (P = 0.019), and gas
      production rate (P = 0.002), and increased butyrate (P = 0.029) and BCVFA (P =
      0.004) proportions and pH (P < 0.001). When the alfalfa hay and concentrate diet
      was used as substrate, CHI decreased butyrate (P < 0.001) and BCVFA (P = 0.008)
      proportions, methane (P = 0.005) and asymptotic gas production (P = 0.02), and
      gas production rate (P = 0.05). In the second trial, CHI decreased NDF apparent
      digestibility (P = 0.09). In conclusion, CHI shifted ruminal fermentation toward
      energetically more efficient routes, without reducing OM apparent digestibility.

PMID- 19854995
TI  - Effect of dam and sire genotypes on productive and carcass traits of rabbits.
AB  - The aim of the experiment was to study the effect of dam and sire genotypes on
      the production and slaughter performance of growing rabbits. The experiment was
      carried out at Kaposvar University. Pannon White (PW) and maternal line (M) does
      were inseminated with the sperm of PW, M, large body line (LB), terminal line of
      Hycole hybrid (H), or colored line (CL) bucks. The mature body size of the M, PW,
      and CL genotypes was medium. The mature body size of the LB and H genotypes was
      large. Only PW and LB rabbits were selected for carcass traits based on computer
      tomograph (CT) scanning data. The rabbits (n = 320) were weaned at the age of 5
      wk and housed in a closed climate-controlled rabbitry in wire cages. Rabbits were
      fed ad libitum a commercial pellet. Rabbits were slaughtered at 78 d of age.
      Daily BW gain (5.7%, P < 0.001) and G:F (6.2%, P < 0.001) of the progeny of PW
      does were better than those of the progeny of the M does. The weight of the
      chilled carcass and body parts was greater for the progeny of the PW does (P <
      0.001). The ratio of the hind part compared with the reference carcass was
      greater in the PW group (P < 0.001); however, the ratio of the fore part was
      greater in the M group (P < 0.05). Examining the effect of the genotype of the
      sires, the BW and daily BW gain were greater in groups H and LB, whereas the
      progeny of M and CL sires were inferior (P < 0.05). Body weights at 11 wk of age
      were H: 2,918 g, LB: 2,793 g, PW: 2,678 g, CL: 2,636 g, and M: 2,585 g (P <
      0.001). Similar differences were found for daily feed intake (P < 0.05). The G:F
      differed (P < 0.05) significantly between groups H and CL. The weights of the
      chilled carcass and of the body parts were the greatest for the progeny of the H
      sires, and the smallest in the M group. The differences between the dressing out
      percentages of the groups were not significant. The ratio of the fore part was
      greater (P < 0.05) in groups LB, H, and CL, but the ratio of the middle part was
      not different. The ratio of hind part related to the reference carcass was
      largest in progeny of PW and least in LB and CL groups (P < 0.05). It was
      concluded that the production of growing rabbits was affected by the adult BW of
      their sires, but the carcass traits were influenced by their own adult BW and by
      the CT-based selection.

PMID- 19854996
TI  - Engaging science in a climate of values: tools for animal scientists tasked with
      addressing ethical problems.
AB  - In the United States, escalating concerns about current farm animal science and
      production methods have resulted not only in increased food animal protection
      policies, but also in animal welfare legislation. Animal scientists and industry
      leaders are apprehensive that such policies may be driven primarily by emotion
      and a lack of scientific understanding, and thus may have unforeseen
      consequences. However, decisions about animal care, and particularly animal
      welfare, cannot be made solely on the basis of science because the potential
      effects on producers, animals, and concerned citizens and the implications for
      the environment and on food prices must also be considered. Balancing the
      interests and values of all stakeholders in regard to animal welfare problems has
      presented a considerable challenge. Ethical accounting processes, such as the
      Ethical Matrix and the ethics assessment process by Campbell, offer models to
      combine socioethical concerns with relevant factual information, thereby
      facilitating decision making that is ethically responsible and that offers viable
      solutions. A case study is used to illustrate application of the ethics
      assessment process by Campbell that includes identification of the ethical
      problems, the embedded values, the relevant facts, and moral tests that can be
      applied. Awareness of these emerging ways of examining ethics that offer real
      solutions to conflicts of interests and not merely "one size fits all" answers
      should be an asset to animal and poultry scientists.

PMID- 19854997
TI  - Influence of dietary protein content and source on fecal quality, electrolyte
      concentrations, and osmolarity, and digestibility in dogs differing in body size.
AB  - When fed the same diet, large-breed dogs tend to produce feces of poorer quality
      compared with small-breed dogs. Moreover, German shepherds, although having a BW
      similar to Giant Schnauzers, are particularly prone to digestive intolerance,
      producing feces of poor consistency and increased moisture. Digestive tolerance
      reflects the reaction of the animal to the diet, and it can be assessed by
      determining fecal quality (consistency, moisture, volume, odor, and color). This
      study was conducted to assess the effect of protein source and content on fecal
      quality, and to determine whether greater digestibility and lesser fecal
      osmolarity and electrolyte concentrations are associated with improved fecal
      quality in dogs differing in body size and digestive tolerance. Twenty-seven
      healthy female dogs were divided into 4 groups according to BW and digestive
      tolerance: small, medium, large tolerant, and large sensitive. Five diets,
      varying in protein source (wheat gluten, poultry meal, and a 50:50 mixture of
      both sources) and concentration (22, 29, and 39% CP on a DM basis for low,
      medium, and high, respectively) were tested. The present study was divided in 2
      phases: 2 diets were studied in a crossover design in phase I, and 3 diets were
      studied in a Latin square design in phase II. Diets were fed for 14 d, followed
      by a 12-d transition period. Fecal score (1 = dry and hard feces, to 5 = liquid
      diarrhea), moisture, electrolytes (Na and K), and osmolarity, and digestibility
      of DM, energy, fat, CP, and ash were determined. Fecal score and moisture (P <
      0.001) were less and overall digestibility (P < 0.001 for DM, CP, fat, ash, and
      energy) was greater for wheat gluten than for poultry meal diets. Large dogs had
      the greatest fecal score and moisture (P < 0.001), together with the greatest
      overall digestibility (P < 0.001 for DM, P = 0.054 for CP, P = 0.005 for ash, and
      P = 0.003 for energy). Osmolarity was less for wheat gluten-based diets (P <
      0.001), and was not affected by dog size. Fecal electrolyte concentration varied
      mainly with dog group (P = 0.005 for Na, and P < 0.001 for K), being greater in
      large sensitive dogs compared with small dogs. Wheat gluten was proved to be a
      suitable protein source for modulating fecal quality in dogs, particularly in
      sensitive breeds. Poorer fecal quality in large sensitive dogs can be related to
      greater digestibility and greater fecal electrolyte concentrations, but not to
      fecal osmolarity.

PMID- 19854998
TI  - Epigenetics and fetal adaptation to perinatal events: diversity through fidelity.
AB  - Perinatal insults, including fetal undernutrition and hypoxia, are associated
      with an increased susceptibility to several adult-onset metabolic disorders.
      These include cardiovascular disease, insulin resistance, and obesity. However,
      the mechanisms driving the long-term phenotypic consequences have only recently
      begun to be elucidated. A primary mechanism accounting for perinatal adaptation
      is the epigenetic modification of chromatin. In this context, epigenetic
      modifications to chromatin are thought to arise in response to a perinatal insult
      in an effort to modulate gene expression and maximize fetal survival. In this
      symposium report, we discuss epigenetics as a mechanism by which perinatal
      adaptations can be made by the developing fetus. We examine the benefits of using
      multiple in vivo models to understand the interrelation of signals that come
      together and result in perinatal adaptation. Epigenetic effects on IGF-1 arising
      from a perinatal insult are discussed, as are the difficulties and challenges
      associated with this complex field. In conclusion, epigenetics provides a means
      of modulating gene transcription, thus allowing fetal adaptation to a broad
      variety of conditions.

PMID- 19854999
TI  - Effect of electron beam irradiation and storage on the quality attributes of
      sausages with different fat contents.
AB  - Sausages with different fat contents (16 or 29%) were purchased from local
      stores, vacuum-packaged in oxygen-impermeable bags, and irradiated at 0 or 5 kGy
      using a linear accelerator. The changes in quality attributes of irradiated
      sausages were determined during storage at 4 degrees C. The 2-thiobarbituric acid
      reactive substance values of sausages were not affected by fat content but were
      increased after irradiation (5 kGy). Storage for 60 d increased the 2
      thiobarbituric acid-reactive substance values of nonirradiated sausages (P <
      0.05) but had no effect on irradiated sausages. The numbers of volatile compounds
      and the amounts of total volatiles were increased by irradiation in both the high
      fat (29% fat) and low-fat (16% fat) sausages. Dimethyl sulfide was detected only
      in irradiated sausages, regardless of fat content (P < 0.05), but it disappeared
      after 60 d of storage. Pentane and 1-heptene were detected only in irradiated
      samples after 60 d of storage. Low-fat sausages had greater L* values, but had
      lesser a* and b* values than high-fat sausages. Irradiation and storage had
      little effect on either the exterior or interior color (L*, a*, and b* values) of
      sausages. Fat content had no effect on the sensory variables of sausages,
      regardless of irradiation and storage. However, irradiated sausages had
      significantly stronger off-odors and off-flavors than nonirradiated sausages
      regardless of fat content (P < 0.05). This indicated that fat content in sausages
      had a minimal effect on the quality of irradiated sausages during storage.

PMID- 19855000
TI  - A multilevel nonlinear mixed-effects approach to model growth in pigs.
AB  - Growth functions have been used to predict market weight of pigs and maximize
      return over feed costs. This study was undertaken to compare 4 growth functions
      and methods of analyzing data, particularly one that considers nonlinear repeated
      measures. Data were collected from an experiment with 40 pigs maintained from
      birth to maturity and their BW measured weekly or every 2 wk up to 1,007 d.
      Gompertz, logistic, Bridges, and Lopez functions were fitted to the data and
      compared using information criteria. For each function, a multilevel nonlinear
      mixed effects model was employed because it allowed for estimation of all growth
      profiles simultaneously, and different sources of variation (i.e., sex, pig, and
      litter effects) were incorporated directly into the parameters. Furthermore,
      variance in-homogeneity and within-pig correlation were introduced to the
      functions. Inclusion of a variance of power function and a continuous
      autoregressive process of first order rendered a substantially improved fit to
      data for all 4 growth functions. The Lopez function provided the best fit to the
      data set and was used for characterizing mean growth curves for the 3 sexes
      (barrows, boars, and gilts). It was estimated that the maximum growth rate occurs
      at 117, 134, and 96 kg of BW for barrows, boars, and gilts, respectively. Hence,
      the gilts reached their maximum growth rate at an earlier stage in life compared
      with boars. Mature size of pigs varied systematically with sex and was estimated
      to be 466, 537, and 382 kg of BW for the barrows, boars, and gilts, respectively.
      These estimates are significantly affected by the duration of the experimental
      period, and it is recommended that future studies looking at estimating the
      mature size in animals are conducted long enough so that the BW visually
      stabilizes. Furthermore, studies should consider adding continuous autoregressive
      process when analyzing nonlinear mixed models with repeated measures.

PMID- 19855001
TI  - Reduced feed intake of lactating primiparous sows is associated with increased
      insulin resistance during the peripartum period and is not modified through
      supplementation with dietary tryptophan.
AB  - The aim of this experiment was to investigate whether insulin resistance is
      related to the dietary concentration of Trp and the ADFI of primiparous sows
      having similar body conditions. Twenty-four primiparous sows were catheterized on
      d 97 of pregnancy. Blood samples were collected during 3 tests: after the
      ingestion of 1.5 kg of feed (meal test), after the intravenous infusion of 0.5 g
      of glucose/kg of BW (glucose tolerance test), and during an euglycemic
      hyperinsulinemic clamp with an infusion rate of 100 ng of insulin x kg of BW(-1)
      x min(-1). Both tests were performed at 4 stages at approximately d 103 and 110
      of pregnancy and at d 3 and 10 of lactation. Sows were fed a diet containing 0.16
      or 0.26% of total Trp (suboptimal vs. slight excessive Trp supply according to
      recommendations for lactating sows) from d 104 of pregnancy after the first clamp
      until weaning. The dietary treatment did not result in differences in ADFI, BW,
      and backfat changes, and growth of piglets during lactation. Plasma Trp
      concentration was greater for the sows allocated to the slight excessive Trp diet
      than for the sows allocated to the suboptimal Trp diet (P < 0.05). Plasma
      glucose, NEFA, and urea profiles during the meal tests were not affected by the
      dietary treatment. At d 3 of lactation, the insulin concentration at 105 (P =
      0.03) and 120 min (P = 0.04) after meal intake was less for the sows allocated to
      the slight excessive Trp diet than for the sows allocated to the suboptimal Trp
      diet. On d 10 of lactation, the glucose half life (P = 0.03) and the time needed
      to reach 25% of the area under the insulin curve (P = 0.04) during the tolerance
      test were less for the sows allocated to the slight excessive Trp diet than for
      the sows allocated to the suboptimal Trp diet. The glucose infusion rate during
      euglycemic hyperinsulinemic clamps was similar in the 2 Trp groups of sows.
      Irrespective of the dietary treatment, the ADFI of the sows was negatively
      related to the glucose half life during the glucose tolerance test and positively
      related to the glucose infusion rate during the clamp (P < 0.05). This
      relationship observed with the tests performed during early lactation was already
      found with the tests performed during late pregnancy (P < 0.02). Present findings
      indicate that a dietary Trp supply of 0.26% does not increase feed intake in
      lactating primiparous sows. This result indicates that the interest in a Trp
      supplementation during the peripartum period can be questioned. Irrespective of
      the dietary treatment, the reasons why sows with similar rearing conditions
      develop different rates of insulin resistance during pregnancy remain to be
      elucidated.

PMID- 19855002
TI  - Potential of low-temperature anaerobic digestion to address current environmental
      concerns on swine production.
AB  - Environmental issues associated with swine production are becoming a major
      concern among the general public and are thus an important challenge for the
      swine industry. There is now a renewed interest in environmental biotechnologies
      that can minimize the impact of swine production and add value to livestock by
      products. An anaerobic biotechnology called psychrophilic anaerobic digestion
      (PAD) in sequencing batch reactors (SBR) has been developed at Agriculture and
      Agri-Food Canada. This very stable biotechnology recovers usable energy,
      stabilizes and deodorizes manure, and increases the availability of plant
      nutrients. Experimental results indicated that PAD of swine manure slurry at 15
      to 25 degrees C in intermittently fed SBR reduces the pollution potential of
      manure by removing up to 90% of the soluble chemical oxygen demand. The process
      performs well under intermittent feeding, once to 3 times a week, and without
      external mixing. Bioreactor feeding activities can thus be easily integrated into
      the routine manure removal procedures in the barn, with minimal interference with
      other farm operations and use of existing manure-handling equipment. Process
      stability was not affected by the presence of antibiotics in manure. The PAD
      process was efficient in eliminating populations of zoonotic pathogens and
      parasites present in raw livestock manure slurries. Psychrophilic anaerobic
      digestion in SBR could also be used for swine mortality disposal. The addition of
      swine carcasses, at loading rates representing up to 8 times the normal mortality
      rates on commercial farms, did not affect the stability of SBR. No operational
      problems were related to the formation of foam and scum. The biotechnology was
      successfully operated at semi-industrial and full commercial scales. Biogas
      production rate exceeded 0.20 L of methane per gram of total chemical oxygen
      demand fed to the SBR. The biogas was of excellent quality, with a methane
      concentration ranging from 70 to 80%. The recovery of green energy, the
      production of a value-added odorless fertilizer, the elimination of manure
      pathogens, and the proper disposal of swine mortalities will substantially reduce
      the carbon and environmental footprints on products of swine origin.

PMID- 19855004
TI  - Murine hematopoietic blast colony-forming cells and their progeny have
      distinctive membrane marker profiles.
AB  - Two distinct bone marrow-derived blast colony-forming cells can generate colonies
      of lineage-restricted progenitor cells in agar cultures of murine bone marrow.
      Both cell types selectively had a Kit(+) ScaI(+) phenotype distinguishing them
      from most lineage-restricted progenitor cells. Multicentric blast colony-forming
      cells stimulated by stem cell factor plus interleukin-6 (IL-6) (BL-CFC-S) were
      separable from most dispersed blast colony-forming cells stimulated by Flt3
      ligand and IL-6 (BL-CFC-F) using CD34 and Flt3R probes. Multicentric BL-CFC-S
      cofractionated with colony-forming units, spleen (CFU-S) supporting the
      possibility that the 2 cells may be identical. The colony populations generated
      by BL-CFC-S were similar in their phenotype and proliferative capacity to
      progenitor cells in whole bone marrow but the progeny of BL-CFC-F were skewed
      with an abnormally high proportion of Kit(-) Flt3R(+) cells whose clonogenic
      cells tended to generate only macrophage progeny. Both blast colony populations
      had a high percentage of GR1(+) and Mac1(+) cells but BL-CFC-F colonies also
      contained a significant population of B220(+) and IL-7R(+) cells relevant to the
      superior ability of BL-CFC-F colony cells to generate B lymphocytes and the known
      dependency of this process on Flt3 ligand and IL-7. The commitment events and
      phenotypic changes during the generation of differing progenitor cells in blast
      colonies can now be clonally analyzed in a convenient in vitro culture system.

PMID- 19855003
TI  - Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor
      cells.
AB  - The mitotic checkpoint has evolved to prevent chromosome mis-segregations by
      delaying mitosis when unattached chromosomes are present. Inducing severe
      chromosome segregation errors by ablating the mitotic checkpoint causes cell
      death. Here we have analyzed the consequences of gradual increases in chromosome
      segregation errors on the viability of tumor cells and normal human fibroblasts.
      Partial reduction of essential mitotic checkpoint components in four tumor cell
      lines caused mild chromosome mis-segregations, but no lethality. These cells
      were, however, remarkably more sensitive to low doses of taxol, which enhanced
      the amount and severity of chromosome segregation errors. Sensitization to taxol
      was achieved by reducing levels of Mps1 or BubR1, proteins having dual roles in
      checkpoint activation and chromosome alignment, but not by reducing Mad2,
      functioning solely in the mitotic checkpoint. Moreover, we find that
      untransformed human fibroblasts with reduced Mps1 levels could not be sensitized
      to sublethal doses of taxol. Thus, targeting the mitotic checkpoint and
      chromosome alignment simultaneously may selectively kill tumor cells by enhancing
      chromosome mis-segregations.

PMID- 19855005
TI  - Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress.
AB  - Type 2 diabetes mellitus (T2DM) results from pancreatic beta cell failure in the
      setting of insulin resistance. Heterozygous mutations in the gene encoding the
      beta cell transcription factor pancreatic duodenal homeobox 1 (Pdx1) are
      associated with both T2DM and maturity onset diabetes of the young (MODY4), and
      low levels of Pdx1 accompany beta cell dysfunction in experimental models of
      glucotoxicity and diabetes. Here, we find that Pdx1 is required for compensatory
      beta cell mass expansion in response to diet-induced insulin resistance through
      its roles in promoting beta cell survival and compensatory hypertrophy. Pdx1
      deficient beta cells show evidence of endoplasmic reticulum (ER) stress both in
      the complex metabolic milieu of high-fat feeding as well as in the setting of
      acutely reduced Pdx1 expression in the Min6 mouse insulinoma cell line. Further,
      Pdx1 deficiency enhances beta cell susceptibility to ER stress-associated
      apoptosis. The results of high throughput expression microarray and chromatin
      occupancy analyses reveal that Pdx1 regulates a broad array of genes involved in
      diverse functions of the ER, including proper disulfide bond formation, protein
      folding, and the unfolded protein response. These findings suggest that Pdx1
      deficiency leads to a failure of beta cell compensation for insulin resistance at
      least in part by impairing critical functions of the ER.

PMID- 19855006
TI  - Finding of residues crucial for supersecondary structure formation.
AB  - This work evaluates the hypothesis that proteins with an identical supersecondary
      structure (SSS) share a unique set of residues--SSS-determining residues--even
      though they may belong to different protein families and have very low sequence
      similarities. This hypothesis was tested on two groups of sandwich-like proteins
      (SPs). Proteins in each group have an identical SSS, but their sequence
      similarity is below the "twilight zone." To find the SSS-determining residues
      specific to each group, a unique structure-based algorithm of multiple sequences
      alignment was developed. The units of alignment are individual strands and loops
      rather than whole sequences. The algorithm is based on the alignment of residues
      that form hydrogen bonds between corresponding strands. Structure-based alignment
      revealed that 30-35% of the positions in the sequences in each group of proteins
      are "conserved positions" occupied either by hydrophobic-only or hydrophilic-only
      residues. Moreover, each group of SPs is characterized by a unique set of SSS
      determining residues found at the conserved positions. The set of SSS-determining
      residues has very high sensitivity and specificity for identifying proteins with
      a corresponding SSS: It is an "amino acid tag" that brands a sequence as having a
      particular SSS. Thus, the sets of SSS-determining residues can be used to
      classify proteins and to predict the SSS of a query amino acid sequence.

PMID- 19855007
TI  - Allosteric control of catalysis by the F loop of RNA polymerase.
AB  - Bacterial RNA polymerases (RNAPs) undergo coordinated conformational changes
      during catalysis. In particular, concerted folding of the trigger loop and
      rearrangements of the bridge helix at the RNAP active center have been implicated
      in nucleotide addition and RNAP translocation. At moderate temperatures, the rate
      of catalysis by RNAP from thermophilic Thermus aquaticus is dramatically reduced
      compared with its closest mesophilic relative, Deinococcus radiodurans. Here, we
      show that a part of this difference is conferred by a third element, the F loop,
      which is adjacent to the N terminus of the bridge helix and directly contacts the
      folded trigger loop. Substitutions of amino acid residues in the F loop and in an
      adjacent segment of the bridge helix in T. aquaticus RNAP for their D.
      radiodurans counterparts significantly increased the rate of catalysis (up to 40
      fold at 20 degrees C). A deletion in the F loop dramatically impaired the rate of
      nucleotide addition and pyrophosphorolysis, but it had only a moderate effect on
      intrinsic RNA cleavage. Streptolydigin, an antibiotic that blocks folding of the
      trigger loop, did not inhibit nucleotide addition by the mutant enzyme. The
      resistance to streptolydigin likely results from the loss of its functional
      target, the folding of the trigger loop, which is already impaired by the F-loop
      deletion. Our results demonstrate that the F loop is essential for proper folding
      of the trigger loop during nucleotide addition and governs the temperature
      adaptivity of RNAPs in different bacteria.

PMID- 19855008
TI  - Exon sequences at the splice junctions affect splicing fidelity and alternative
      splicing.
AB  - Identification of splice sites is essential for the expression of most eukaryotic
      genes, allowing accurate splicing of pre-mRNAs. The splice sites are recognized
      by the splicing machinery based on sequences within the pre-mRNA. Here, we show
      that the exon sequences at the splice junctions play a significant, previously
      unrecognized role in the selection of 3' splice sites during the second step of
      splicing. The influence of the exon sequences was enhanced by the Prp18 mutant
      Prp18DeltaCR, and the strength of an exon sequence in Prp18DeltaCR splicing
      predicted its effect in wild-type splicing. Analysis of the kinetics of splicing
      in vitro demonstrated that 3' splice sites were chosen competitively during the
      second step, likely at the same time as exon ligation. In wild-type yeast, splice
      site selection for two genes studied was altered by point mutations in their exon
      bases, affecting splicing fidelity and alternative splicing. Finally, we note
      that the degeneracy of the genetic code allows competing 3' splice sites to be
      eliminated from coding regions, and we suggest that the evolution of the splicing
      signals and the genetic code are connected.

PMID- 19855009
TI  - Shifting the genomic gold standard for the prokaryotic species definition.
AB  - DNA-DNA hybridization (DDH) has been used for nearly 50 years as the gold
      standard for prokaryotic species circumscriptions at the genomic level. It has
      been the only taxonomic method that offered a numerical and relatively stable
      species boundary, and its use has had a paramount influence on how the current
      classification has been constructed. However, now, in the era of genomics, DDH
      appears to be an outdated method for classification that needs to be substituted.
      The average nucleotide identity (ANI) between two genomes seems the most
      promising method since it mirrors DDH closely. Here we examine the work package
      JSpecies as a user-friendly, biologist-oriented interface to calculate ANI and
      the correlation of the tetranucleotide signatures between pairwise genomic
      comparisons. The results agreed with the use of ANI to substitute DDH, with a
      narrowed boundary that could be set at approximately 95-96%. In addition, the
      JSpecies package implemented the tetranucleotide signature correlation index, an
      alignment-free parameter that generally correlates with ANI and that can be of
      help in deciding when a given pair of organisms should be classified in the same
      species. Moreover, for taxonomic purposes, the analyses can be produced by simply
      randomly sequencing at least 20% of the genome of the query strains rather than
      obtaining their full sequence.

PMID- 19855010
TI  - Notch1 signaling plays a role in regulating precursor differentiation during CNS
      remyelination.
AB  - In the developing CNS, Notch1 and its ligand, Jagged1, regulate oligodendrocyte
      differentiation and myelin formation, but their role in repair of demyelinating
      lesions in diseases such as multiple sclerosis remains unresolved. To address
      this question, we generated a mouse model in which we targeted Notch1
      inactivation to oligodendrocyte progenitor cells (OPCs) using Olig1Cre and a
      floxed Notch1 allele, Notch1(12f). During CNS development, OPC differentiation
      was potentiated in Olig1Cre:Notch1(12f/12f) mice. Importantly, in adults,
      remyelination of demyelinating lesions was also accelerated, at the expense of
      proliferation within the progenitor population. Experiments in vitro confirmed
      that Notch1 signaling was permissive for OPC expansion but inhibited
      differentiation and myelin formation. These studies also revealed that astrocytes
      exposed to TGF-beta1 restricted OPC maturation via Jagged1-Notch1 signaling.
      These data suggest that Notch1 signaling is one of the mechanisms regulating OPC
      differentiation during CNS remyelination. Thus, Notch1 may represent a potential
      therapeutical avenue for lesion repair in demyelinating disease.

PMID- 19855011
TI  - Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme
      lysyl oxidase.
AB  - Great arteries, as well as lungs and skin, contain elastic fibers as important
      components to maintain their physiological functions. Although recent studies
      have revealed that a glycoprotein fibulin-4 (FBLN4) is indispensable for the
      assembly of mature elastic fibers, it remains to be elucidated how FBLN4 takes
      part in elastogenesis. Here, we report a dose-dependent requirement for FBLN4 in
      the development of the elastic fibers in arteries, and a specific role of FBLN4
      in recruiting the elastin-cross-linking enzyme, lysyl oxidase (LOX). Reduced
      expression of Fbln4, which was achieved with a smooth muscle-specific Cre
      mediated gene deletion, caused arterial stiffness. Electron-microscopic
      examination revealed disorganized thick elastic laminae with aberrant deposition
      of elastin. Aneurysmal dilation of the ascending aorta was found when the Fbln4
      expression level was reduced to an even lower level, whereas systemic Fbln4 null
      mice died perinatally from rupture of the diaphragm. We also found a specific
      interaction between FBLN4 and the propeptide of LOX, which efficiently promotes
      assembly of LOX onto tropoelastin. These data suggest a mechanism of
      elastogenesis, in which a sufficient amount of FBLN4 is essential for tethering
      LOX to tropoelastin to facilitate cross-linking.

PMID- 19855012
TI  - TGFbeta family signaling: novel insights in development and disease.
AB  - Advances in our understanding of the many levels of regulation of TGFbeta and BMP
      signaling were reported at the recent FASEB Summer Conference entitled ;The
      TGFbeta Superfamily: Development and Disease', which was held in Carefree,
      Arizona, USA, on the northern edge of the Sonoran Desert. This conference was the
      fifth meeting in a biannual FASEB conference series and, as with the previous
      meetings, brought together biochemists, geneticists, developmental and tissue
      biologists interested in the inter-workings of TGFbeta/BMP signaling pathways and
      in the consequences of these pathways going awry.

PMID- 19855013
TI  - The regulation of TGFbeta signal transduction.
AB  - Transforming growth factor beta (TGFbeta) pathways are implicated in metazoan
      development, adult homeostasis and disease. TGFbeta ligands signal via receptor
      serine/threonine kinases that phosphorylate, and activate, intracellular Smad
      effectors as well as other signaling proteins. Oligomeric Smad complexes
      associate with chromatin and regulate transcription, defining the biological
      response of a cell to TGFbeta family members. Signaling is modulated by negative
      feedback regulation via inhibitory Smads. We review here the mechanisms of
      TGFbeta signal transduction in metazoans and emphasize events crucial for
      embryonic development.

PMID- 19855014
TI  - The extracellular regulation of bone morphogenetic protein signaling.
AB  - In many cases, the level, positioning and timing of signaling through the bone
      morphogenetic protein (BMP) pathway are regulated by molecules that bind BMP
      ligands in the extracellular space. Whereas many BMP-binding proteins inhibit
      signaling by sequestering BMPs from their receptors, other BMP-binding proteins
      cause remarkably context-specific gains or losses in signaling. Here, we review
      recent findings and hypotheses on the complex mechanisms that lead to these
      effects, with data from developing systems, biochemical analyses and mathematical
      modeling.

PMID- 19855015
TI  - Informatics approaches to understanding TGFbeta pathway regulation.
AB  - In recent years, informatics studies have predicted several new ways in which the
      transforming growth factor beta (TGFbeta) signaling pathway can be post
      translationally regulated. Subsequently, many of these predictions were
      experimentally validated. These approaches include phylogenetic predictions for
      the phosphorylation, sumoylation and ubiquitylation of pathway components, as
      well as kinetic models of endocytosis, phosphorylation and nucleo-cytoplasmic
      shuttling. We review these studies and provide a brief ;how to' guide for
      phylogenetics. Our hope is to stimulate experimental tests of informatics-based
      predictions for TGFbeta signaling, as well as for other signaling pathways, and
      to expand the number of developmental pathways that are being analyzed
      computationally.

PMID- 19855016
TI  - The Id2+ distal tip lung epithelium contains individual multipotent embryonic
      progenitor cells.
AB  - The conducting airways (bronchi and bronchioles) and peripheral gas exchange
      (alveolar) regions of the mammalian lung are generated by a process of branching
      morphogenesis. Evidence suggests that during embryonic development, the
      undifferentiated epithelial progenitors are located at the distal tips of the
      branching epithelium. To test this hypothesis, we used an Id2-CreER(T2) knock-in
      mouse strain to lineage trace the distal epithelial tip cells during either the
      pseudoglandular or canalicular phases of development. During the pseudoglandular
      stage, the tip cells both self-renew and contribute descendents to all epithelial
      cell lineages, including neuroendocrine cells. In addition, individual Id2(+) tip
      cells can self-renew and contribute descendents to both the bronchiolar and
      alveolar compartments. By contrast, during the later canalicular stage, the
      distal epithelial tip cells only contribute descendents to the alveoli. Taken
      together, this evidence supports a model in which the distal tip of the
      developing lung contains a multipotent epithelial population, the fate of which
      changes during development.

PMID- 19855017
TI  - Cell competition, growth and size control in the Drosophila wing imaginal disc.
AB  - We report here experiments aimed at understanding the connections between cell
      competition and growth in the Drosophila wing disc. The principal assay has been
      to generate discs containing marked cells that proliferate at different rates and
      to study their interactions and their contribution to the final structure. It is
      known that single clones of fast-dividing cells within a compartment may occupy
      the larger part of the compartment without affecting its size. This has suggested
      the existence of interactions involving cell competition between fast- and slow
      dividing cells directed to accommodate the contribution of each cell to the final
      compartment. Here we show that indeed fast-dividing cells can outcompete slow
      dividing ones in their proximity. However, we argue that this elimination is of
      little consequence because preventing apoptosis, and therefore cell competition,
      in those compartments does not affect the size of the clones or the size of the
      compartments. Our experiments indicate that cells within a compartment
      proliferate autonomously at their own rate. The contribution of each cell to the
      compartment is exclusively determined by its division rate within the frame of a
      size control mechanism that stops growth once the compartment has reached the
      final arresting size. This is supported by a computer simulation of the
      contribution of individual fast clones growing within a population of slower
      dividing cells and without interacting with them. The values predicted by the
      simulation are very close to those obtained experimentally.

PMID- 19855018
TI  - Mitochondrial protein Preli-like is required for development of dendritic arbors
      and prevents their regression in the Drosophila sensory nervous system.
AB  - Dynamic morphological changes in mitochondria depend on the balance of fusion and
      fission in various eukaryotes, and are crucial for mitochondrial activity.
      Mitochondrial dysfunction has emerged as a common theme that underlies numerous
      neurological disorders, including neurodegeneration. However, how this abnormal
      mitochondrial activity leads to neurodegenerative disorders is still largely
      unknown. Here, we show that the Drosophila mitochondrial protein Preli-like
      (Prel), a member of the conserved PRELI/MSF1 family, contributes to the integrity
      of mitochondrial structures, the activity of respiratory chain complex IV and the
      cellular ATP level. When Prel function was impaired in neurons in vivo, the
      cellular ATP level decreased and mitochondria became fragmented and sparsely
      distributed in dendrites and axons. Notably, the dendritic arbors were simplified
      and downsized, probably as a result of breakage of proximal dendrites and
      progressive retraction of terminal branches. By contrast, abrogation of the
      mitochondria transport machinery per se had a much less profound effect on the
      arbor morphogenesis. Interestingly, overexpression of Drob-1 (Debcl), a
      Drosophila Bax-like Bcl-2 family protein, in the wild-type background produced
      dendrite phenotypes that were reminiscent of the prel phenotype. Moreover,
      expression of the Drob-1 antagonist Buffy in prel mutant neurons substantially
      restored the dendritic phenotype. Our observations suggest that Prel-dependent
      regulation of mitochondrial activity is important for both growth and prevention
      of breakage of dendritic branches.

PMID- 19855019
TI  - Conserved regulatory sequences in Atoh7 mediate non-conserved regulatory
      responses in retina ontogenesis.
AB  - The characterisation of interspecies differences in gene regulation is crucial to
      understanding the molecular basis of phenotypic diversity and evolution. The
      atonal homologue Atoh7 participates in the ontogenesis of the vertebrate retina.
      Our study reveals how evolutionarily conserved, non-coding DNA sequences mediate
      both the conserved and the species-specific transcriptional features of the Atoh7
      gene. In the mouse and chick retina, species-related variations in the chromatin
      binding profiles of bHLH transcription factors correlate with distinct features
      of the Atoh7 promoters and underlie variations in the transcriptional rates of
      the Atoh7 genes. The different expression kinetics of the Atoh7 genes generate
      differences in the expression patterns of a set of genes that are regulated by
      Atoh7 in a dose-dependent manner, including those involved in neurite outgrowth
      and growth cone migration. In summary, we show how highly conserved regulatory
      elements are put to use in mediating non-conserved functions and creating
      interspecies neuronal diversity.

PMID- 19855020
TI  - A BMP-Shh negative-feedback loop restricts Shh expression during limb
      development.
AB  - Normal patterning of tissues and organs requires the tight restriction of
      signaling molecules to well-defined organizing centers. In the limb bud, one of
      the main signaling centers is the zone of polarizing activity (ZPA) that controls
      growth and patterning through the production of sonic hedgehog (SHH). The
      appropriate temporal and spatial expression of Shh is crucial for normal limb bud
      patterning, because modifications, even if subtle, have important phenotypic
      consequences. However, although there is a lot of information about the factors
      that activate and maintain Shh expression, much less is known about the
      mechanisms that restrict its expression to the ZPA. In this study, we show that
      BMP activity negatively regulates Shh transcription and that a BMP-Shh negative
      feedback loop serves to confine Shh expression. BMP-dependent downregulation of
      Shh is achieved by interfering with the FGF and Wnt signaling activities that
      maintain Shh expression. We also show that FGF induction of Shh requires protein
      synthesis and is mediated by the ERK1/2 MAPK transduction pathway. BMP gene
      expression in the posterior limb bud mesoderm is positively regulated by FGF
      signaling and finely regulated by an auto-regulatory loop. Our study emphasizes
      the intricacy of the crosstalk between the major signaling pathways in the
      posterior limb bud.

PMID- 19855021
TI  - Zebrafish zic2a patterns the forebrain through modulation of Hedgehog-activated
      gene expression.
AB  - Holoprosencephaly (HPE) is the most common congenital malformation of the
      forebrain in human. Several genes with essential roles during forebrain
      development have been identified because they cause HPE when mutated. Among these
      are genes that encode the secreted growth factor Sonic hedgehog (Shh) and the
      transcription factors Six3 and Zic2. In the mouse, Six3 and Shh activate each
      other's transcription, but a role for Zic2 in this interaction has not been
      tested. We demonstrate that in zebrafish, as in mouse, Hh signaling activates
      transcription of six3b in the developing forebrain. zic2a is also activated by Hh
      signaling, and represses six3b non-cell-autonomously, i.e. outside of its own
      expression domain, probably through limiting Hh signaling. Zic2a repression of
      six3b is essential for the correct formation of the prethalamus. The diencephalon
      derived optic stalk (OS) and neural retina are also patterned in response to Hh
      signaling. We show that zebrafish Zic2a limits transcription of the Hh targets
      pax2a and fgf8a in the OS and retina. The effects of Zic2a depletion in the
      forebrain and in the OS and retina are rescued by blocking Hh signaling or by
      increasing levels of the Hh antagonist Hhip, suggesting that in both tissues
      Zic2a acts to attenuate the effects of Hh signaling. These data uncover a novel,
      essential role for Zic2a as a modulator of Hh-activated gene expression in the
      developing forebrain and advance our understanding of a key gene regulatory
      network that, when disrupted, causes HPE.

PMID- 19855022
TI  - Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve
      ring placement in C. elegans.
AB  - Wnt signaling through Frizzled proteins guides posterior cells and axons in C.
      elegans into different spatial domains. Here we demonstrate an essential role for
      Wnt signaling through Ror tyrosine kinase homologs in the most prominent anterior
      neuropil, the nerve ring. A genetic screen uncovered cwn-2, the C. elegans
      homolog of Wnt5, as a regulator of nerve ring placement. In cwn-2 mutants, all
      neuronal structures in and around the nerve ring are shifted to an abnormal
      anterior position. cwn-2 is required at the time of nerve ring formation; it is
      expressed by cells posterior of the nerve ring, but its precise site of
      expression is not critical for its function. In nerve ring development, cwn-2
      acts primarily through the Wnt receptor CAM-1 (Ror), together with the Frizzled
      protein MIG-1, with parallel roles for the Frizzled protein CFZ-2. The
      identification of CAM-1 as a CWN-2 receptor contrasts with CAM-1 action as a non
      receptor in other C. elegans Wnt pathways. Cell-specific rescue of cam-1 and cell
      ablation experiments reveal a crucial role for the SIA and SIB neurons in
      positioning the nerve ring, linking Wnt signaling to specific cells that organize
      the anterior nervous system.

PMID- 19855023
TI  - The entire zebrafish blastula-gastrula margin acts as an organizer dependent on
      the ratio of Nodal to BMP activity.
AB  - Formation of the vertebrate embryo is known to depend on the activity of
      organizing centers. The dorsal Spemann organizer is the source of growth factor
      antagonists that participate in the creation of signaling gradients. In various
      species, the existence of head, trunk and trunk-tail inducers has been proposed
      to explain the formation of different parts of the embryo along the
      anteroposterior (A/P) axis. In zebrafish, two organizing centers have been
      described, the dorsal and tail organizers, located at the dorsal and ventral
      gastrula margins, respectively. Here, we report that organizer functions are
      executed not only by the dorsal and ventral margins, but also by all parts of the
      blastula-gastrula margin. The position of different marginal territories along
      the dorsoventral axis defines the A/P nature of the structures they are able to
      organize. At the molecular level, we show that this organizing activity results
      from the simultaneous activation of BMP and Nodal signaling pathways.
      Furthermore, the A/P character of the organized structures is not defined by
      absolute levels but instead by the ratio of BMP and Nodal activities. Rather than
      resulting from the activity of discrete centers, organization of the zebrafish
      embryo depends on the activity of the entire margin acting as a continuous and
      global organizer that is established by a gradual ventral-to-dorsal modulation of
      the ratio of marginal BMP to Nodal activity.

PMID- 19855025
TI  - Algorithm of myogenic differentiation in higher-order organisms.
AB  - Cell fate determination is governed by complex signaling molecules at appropriate
      concentrations that regulate the cell decision-making process. In vertebrates,
      however, concentration and kinetic parameters are practically unknown, and
      therefore the mechanism by which these molecules interact is obscure. In
      myogenesis, for example, multipotent cells differentiate into skeletal muscle as
      a result of appropriate interplay between several signaling molecules, which is
      not sufficiently characterized. Here we demonstrate that treatment of biochemical
      events with SAT (satisfiability) formalism, which has been primarily applied for
      solving decision-making problems, can provide a simple conceptual tool for
      describing the relationship between causes and effects in biological phenomena.
      Specifically, we applied the Lukasiewicz logic to a diffusible protein system
      that leads to myogenesis. The creation of an automaton that describes the
      myogenesis SAT problem has led to a comprehensive overview of this non-trivial
      phenomenon and also to a hypothesis that was subsequently verified
      experimentally. This example demonstrates the power of applying Lukasiewicz logic
      in describing and predicting any decision-making problem in general, and
      developmental processes in particular.

PMID- 19855024
TI  - The establishment of sexual identity in the Drosophila germline.
AB  - The establishment of sexual identity is a crucial step of germ cell development
      in sexually reproducing organisms. Sex determination in the germline is
      controlled differently than in the soma, and often depends on communication from
      the soma. To investigate how sexual identity is established in the Drosophila
      germline, we first conducted a molecular screen for genes expressed in a sex
      specific manner in embryonic germ cells. Sex-specific expression of these genes
      is initiated at the time of gonad formation (stage 15), indicating that sexual
      identity in the germline is established by this time. Experiments where the sex
      of the soma was altered relative to that of the germline (by manipulating
      transformer) reveal a dominant role for the soma in regulating initial germline
      sexual identity. Germ cells largely take on the sex of the surrounding soma,
      although the sex chromosome constitution of the germ cells still plays some role
      at this time. The male soma signals to the germline through the JAK/STAT pathway,
      while the nature of the signal from the female soma remains unknown. We also find
      that the genes ovo and ovarian tumor (otu) are expressed in a female-specific
      manner in embryonic germ cells, consistent with their role in promoting female
      germline identity. However, removing the function of ovo and otu, or reducing
      germline function of Sex lethal, had little effect on establishment of germline
      sexual identity. This is consistent with our findings that signals from the soma
      are dominant over germline autonomous cues at the initial stage of germline sex
      determination.

PMID- 19855026
TI  - LIM homeodomain transcription factor-dependent specification of bipotential MGE
      progenitors into cholinergic and GABAergic striatal interneurons.
AB  - Coordination of voluntary motor activity depends on the generation of the
      appropriate neuronal subtypes in the basal ganglia and their integration into
      functional neuronal circuits. The largest nucleus of the basal ganglia, the
      striatum, contains two classes of neurons: the principal population of medium
      sized dense spiny neurons (MSNs; 97-98% of all striatal neurons in rodents),
      which project to the globus pallidus and the substantia nigra, and the locally
      projecting striatal interneurons (SINs; 2-3% in rodents). SINs are further
      subdivided into two non-overlapping groups: those producing acetylcholine
      (cholinergic) and those producing gamma-amino butyric acid (GABAergic). Despite
      the pivotal role of SINs in integrating the output of striatal circuits and the
      function of neuronal networks in the ventral forebrain, the lineage relationship
      of SIN subtypes and the molecular mechanisms that control their differentiation
      are currently unclear. Using genetic fate mapping, we demonstrate here that the
      majority of cholinergic and GABAergic SINs are derived from common precursors
      generated in the medial ganglionic eminence during embryogenesis. These
      precursors express the LIM homeodomain protein Lhx6 and have characteristics of
      proto-GABAergic neurons. By combining gene expression analysis with loss-of
      function and misexpression experiments, we provide evidence that the
      differentiation of the common precursor into mature SIN subtypes is regulated by
      the combinatorial activity of the LIM homeodomain proteins Lhx6, Lhx7 (Lhx8) and
      Isl1. These studies suggest that a LIM homeodomain transcriptional code confers
      cell-fate specification and neurotransmitter identity in neuronal subpopulations
      of the ventral forebrain.

PMID- 19855027
TI  - Impact of bereavement on progression of AIDS and HIV infection: a review.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) disease is associated with
      bereavement and grief reactions brought about by the disease process itself and
      by the losses of loved ones. OBJECTIVE: The goal of this review is to assess the
      current literature regarding grief, HIV, and immunity. METHOD: The authors
      reviewed applicable articles retrieved from a MEDLINE literature search with the
      search terms "bereavement/HIV," "grief/HIV," and "immunity/grief/HIV." RESULTS:
      Data continue to emerge that suggest a profound role for bereavement in mediating
      HIV illness and the need to effectively deal with bereavement issues.
      CONCLUSIONS: Patients who experience maladaptive grief show more rapid losses of
      CD4 T-cells over time, even when controlling for age, health status, use of
      antiretrovirals, and illicit drug abuse. This immune dysfunction may be managed
      by a variety of psychotherapeutic techniques.

PMID- 19855028
TI  - Cancer-related fatigue and its associations with depression and anxiety: a
      systematic review.
AB  - BACKGROUND: Fatigue is an important symptom in cancer and has been shown to be
      associated with psychological distress. OBJECTIVE: This review assesses evidence
      regarding associations of cancer-related fatigue with depression and anxiety.
      METHOD: Database searches yielded 59 studies reporting correlation coefficients
      or odds ratios. RESULTS: The combined sample size was 12,103. Almost all studies
      showed a correlation of fatigue with depression and with anxiety. However, 31
      different instruments were used to assess fatigue, suggesting a lack of consensus
      on measurement. CONCLUSION: This review confirms the association of fatigue with
      depression and anxiety. Directionality needs to be better delineated in
      longitudinal studies.

PMID- 19855029
TI  - Pattern of depressive symptoms in Parkinson's disease.
AB  - BACKGROUND: Depressive symptoms are common in Parkinson's disease (PD); however,
      it is unclear whether there are specific depressive symptom patterns in patients
      with PD and comorbid depression (dPD). OBJECTIVE: The goal of this study is to
      examine the frequency and correlates of specific depressive symptoms in PD.
      METHOD: A sample of 158 individuals with PD completed the self-rated Harvard
      Department of Psychiatry/National Depression Screening Day Scale (HANDS). By
      multiple-regression analysis, the authors examined the association between HANDS
      total and subscale scores and various demographic variables. RESULTS: The
      frequency of depression was 37% (N=58). Patients with a history of depression
      before PD had significantly more serious depression than those who had no such
      history. Of those who were more depressed, the most common symptoms of depression
      endorsed were low energy, difficulty with concentration/making decisions, feeling
      blue, feeling hopeless, and having poor sleep. CONCLUSION: There is a relatively
      high prevalence of dPD. Items on the HANDS that discriminated best between
      depressed and nondepressed subjects with PD included feeling blue, feeling
      hopeless, feeling worthless, lack of interest, and self-blame. It remains to be
      defined whether dPD should be understood primarily as a psychological reaction to
      a physical disability or perceived impending one, or as a direct expression of
      the neuropathology of PD.

PMID- 19855030
TI  - Fatigue in psychiatric HIV patients: a pilot study of psychological correlates.
AB  - BACKGROUND: Even though viral management of HIV infection is now more effective,
      clinical observations suggest that fatigue remains a problem for a substantial
      proportion of patients. OBJECTIVE: The authors delineated prevalence and severity
      of fatigue in HIV patients with psychiatric comorbidities and examined
      psychological correlates of fatigue. METHOD: The authors comprehensively assessed
      fatigue in 38 consecutive HIV patients referred for psychiatric treatment with
      the Identity-Consequence Fatigue Scale. RESULTS: About 80% of patients reported
      at least moderate feelings of fatigue, and about 25% judged that fatigue was
      severely affecting their daily functioning. Depression, anxiety, and perceived
      stress explained between 20% and 75% of the variance in fatigue ratings.
      DISCUSSION: The results suggest that fatigue in the era of effective
      antiretroviral treatment is prevalent, relevant, and related to psychological
      morbidities. Recognition and treatment of these comorbidities may be important in
      reducing this fatigue.

PMID- 19855031
TI  - Poor perceived social support in implantable cardioverter defibrillator (ICD)
      patients and their partners: cross-validation of the multidimensional scale of
      perceived social support.
AB  - BACKGROUND: Social support is a known buffer of psychological distress and has
      also been shown to influence adverse medical outcomes. OBJECTIVE: The authors
      investigated the role of social support and its correlates in patients with an
      implantable cardioverter defibrillator (ICD) and their partners. METHOD: The
      authors cross-validated the Multidimensional Scale of Perceived Social Support
      (MSPSS) in Danish and Dutch cardiac patients and their partners and examined
      correlates of poor support. RESULTS: The three-factor structure of the MSPSS, its
      validity, and internal consistency were confirmed, with the test-retest
      reliability found to be lower than in previous studies. Being an ICD patient or
      an ICD partner, as compared with a chronic heart failure (CHF) patient, having no
      partner, and having a Type D personality were correlates of poor support,
      independent of anxiety and depressive symptoms. CONCLUSIONS: The validity and
      reliability of the MSPSS were confirmed in a mixed group of Dutch and Danish
      cardiac patients and their partners. Preliminary findings indicate that ICD
      patients and their partners may be more in need of support than CHF patients.

PMID- 19855032
TI  - Psychiatric evaluation of mental capacity in the general hospital: a significant
      teaching opportunity.
AB  - BACKGROUND: Requests for evaluation of mental capacity in general hospitals have
      increased in frequency. OBJECTIVE: The authors sought to determine the
      interventions required to respond adequately and assess the initiating
      circumstances. METHOD: Questionnaires completed by psychiatric consultants were
      analyzed, and chart reviews were completed. RESULTS: Capacity evaluation alone
      resolved 32% of the requests; 31% required an evaluation plus additional
      interventions; 37% did not require a capacity evaluation. Patients threatening to
      leave against advice, and/or refusing treatments or procedures represented 64% of
      requests. Consultants successfully resolved 88% of such cases. CONCLUSION: A
      mental capacity evaluation alone was insufficient to resolve two-thirds of
      problems eliciting requests. Consultation-liaison psychiatrists can use these
      evaluations as teaching opportunities.

PMID- 19855033
TI  - Obesity and quality of life: a controlled study of normal-weight and obese
      individuals.
AB  - BACKGROUND: Obesity is a major public health problem that is associated with
      substantial morbidity and mortality. OBJECTIVE: The authors investigated the
      associations between health-related quality of life (HRQL) and Body Mass Index
      (BMI), gender, age, mental and somatic disorders, as well as therapy-seeking
      status. METHOD: A cross-sectional controlled study assessed 640 male and female
      individuals, clustered into four weight categories. RESULTS: Linear-regression
      analyses revealed that higher BMI, higher age, and higher numbers of current
      somatic and mental disorders negatively predicted the physical dimension of HRQL.
      Higher numbers of both mental and somatic disorders as well as female gender and
      younger age seemed to be independent negative predictors of mental HRQL, whereas
      BMI was not associated with mental HRQL. Therapy status was not related to mental
      or physical HRQL. CONCLUSION: Physical and mental disorders are important
      detrimental factors for both physical and mental dimensions of HRQL.

PMID- 19855034
TI  - Anxiety predicts poor perceived health in patients with an implantable
      defibrillator.
AB  - BACKGROUND: Implantation with an implantable cardioverter defibrillator (ICD) may
      cause psychological problems, including anxiety. OBJECTIVE: The objective was to
      determine whether general anxiety and disease-specific anxiety differentially
      predict poor perceived health in ICD patients. RESULTS: Patient concerns about
      the ICD and feelings of disability were independently predicted by general as
      well as disease-specific anxiety. Clinical anxiety was predicted by general
      anxiety only, whereas cardiopulmonary symptoms were predicted by disease-specific
      anxiety. CONCLUSION: Identifying and supporting ICD patients with various anxiety
      symptoms is important. Future research should examine the differential predictive
      value of different forms of anxiety toward medical endpoints as well as possible
      interventions for disease-related anxiety.

PMID- 19855035
TI  - Minor depression as a short-term risk factor in outpatients with congestive heart
      failure.
AB  - BACKGROUND: In the past decade, there has been an increasing awareness of both
      quality-of-life impairment and the negative prognostic role of depression in
      congestive heart failure (CHF) patients. OBJECTIVE: The aims of this study were
      to evaluate distress, psychological well-being, and clinical and subclinical
      depression in 68 CHF outpatients at Bellaria Hospital in Bologna, Italy, at an
      initial assessment and at a 2-month routine follow-up visit. RESULTS: Patients
      reported a high prevalence of somatic complaints, depression, and demoralization,
      and low scores on psychological well-being. Among the variables examined as
      potential risk factors for cardiovascular outcome events, based on
      rehospitalization and cardiac death, only minor depression attained statistical
      significance. CONCLUSION: Clinicians should thus assess minor depression among
      other psychological variables in these patients.

PMID- 19855036
TI  - Antiviral completion rates and sustained viral response in hepatitis C patients
      with and without preexisting major depressive disorder.
AB  - BACKGROUND: Despite evidence suggesting that the majority of patients with
      hepatitis C virus (HCV) have psychiatric and substance use disorders, patients
      with these comorbidities have historically been excluded from antiviral therapy
      for HCV. OBJECTIVE: The authors compared antiviral completion and sustained
      virologic response (SVR) rates between hepatitis C (HCV) patients with versus
      those without preexisting major depressive disorder (MDD). METHOD: The authors
      performed a chart review of HCV patients (30 with MDD and 25 control subjects)
      who attended an optional HCV education class and signed informed consent allowing
      collection of clinical data. RESULTS: The MDD group had completion and SVR rates
      similar to those of control subjects. Neuropsychiatric side effects and reasons
      for discontinuation of treatment were not different between groups. CONCLUSION:
      Patients with MDD can be safely and effectively treated with antiviral therapy.

PMID- 19855037
TI  - Symptoms of depression and delirium assessed serially in palliative-care
      inpatients.
AB  - BACKGROUND: Delirium occurs in approximately 1 in 5 general hospital admissions
      and up to 85% of patients with terminal illness, but can be difficult to
      differentiation from other disorders, such as depression. OBJECTIVE: The authors
      assessed and compared mood states as they relate to onset of delirium. METHOD:
      Symptoms of depression and delirium were assessed in 100 consecutive palliative
      care admissions immediately after admission and 1 week later. RESULTS: Overall,
      51% experienced either major depression or delirium. Most patients with syndromal
      delirium also met criteria for major depressive illness, and 50% of those with
      depression had delirium or subsyndromal delirium (SSD). Delirium symptoms were
      less common in patients with major depression than depressive symptoms in
      patients with delirium or SSD. DISCUSSION: Delirium should be considered in
      patients with altered mood states, and screening for depression should initially
      rule out delirium. Sustained alterations in mood may be more frequent in delirium
      than previously recognized.

PMID- 19855038
TI  - Medically unexplained physical symptoms in primary care: a controlled study on
      the effectiveness of cognitive-behavioral treatment by the family physician.
AB  - BACKGROUND: Disabling medically unexplained physical symptoms occur in 16% of all
      patients in primary care. OBJECTIVE: The aim of this study was to assess the
      effectiveness of a cognitive-behavioral intervention by the family physician.
      METHOD: In a controlled design with detailed information on patient selection,
      6,409 patients were screened on somatoform disorder, and 65 participants were
      allocated to care-as-usual or the experimental condition. RESULTS: After 6 and 12
      months, the cognitive-behavioral intervention by trained family physicians was
      not more effective than care-as-usual. CONCLUSION: Possibly, the intensity of
      treatment was insufficient for the severe and persistent symptoms that were
      encountered in primary care.

PMID- 19855039
TI  - Religiosity and hope: a path for women coping with a diagnosis of breast cancer.
AB  - BACKGROUND: Both religiosity and hope are known for their positive role in coping
      with cancer. OBJECTIVE: This study examines the mediating role of hope between
      religiosity and coping for women diagnosed with breast cancer. METHOD: Israeli
      Jewish women with breast cancer (N=233) completed the Mental Adjustment to Cancer
      Scale, The Systems of Belief Inventory, and The Hope Scale. RESULTS: By use of
      hierarchical regression, hope was found to be a mediator between religiosity and
      three coping styles. CONCLUSION: Special attention should be given to the role of
      hope for religious patients because it increases the positive effects of religion
      in coping with cancer.

PMID- 19855040
TI  - Delusion of oral parasitosis and thalamic pain syndrome.
AB  - BACKGROUND: Delusional parasitosis is an uncommon psychiatric condition in which
      patients have the immutable conviction that small, living organisms, such as
      worms, insects, or larvae infest their skin or other organs. OBJECTIVE/METHOD:
      The authors describe a case of an unusual association of delusional parasitosis
      and thalamic pain syndrome after left-posterior thalamic hemorrhage. The patient
      initially suffered from dysesthesia and burning pain typical of thalamic pain
      syndrome and subsequently developed delusional oral parasitosis ("worms"
      infesting her mouth). RESULTS: Sulpiride 100 mg/day administered in addition to
      amitriptyline gradually improved her delusions within 3 months. DISCUSSION: The
      authors speculate that this specific type of delusion can be elicited by the
      disruption of the somatosensory pathway and that the subsequent cortical sensory
      deafferentiation and reorganization arising from this disruption may contribute
      to the development of delusional parasitosis.

PMID- 19855041
TI  - Prolonged psychosis associated with interferon therapy in a patient with
      hepatitis C: case study and literature review.
AB  - BACKGROUND: Although rare, psychosis can emerge during interferon (IFN)-alpha
      therapy and persist after therapy is completed. OBJECTIVE: The authors report the
      case of a 30-year-old man with hepatitis C infection treated with IFN-alpha and
      ribavirin who developed acute psychosis with persecutory delusions and auditory
      hallucinations, resulting in a suicide attempt. METHOD: The patient was treated
      with amisulpride for 6 weeks and then with risperidone for 6 weeks. RESULTS:
      There was no improvement in symptoms until the patient was treated with
      quetiapine; he then had a marked recovery from the psychotic symptoms. The
      duration of the psychosis was 28 weeks. CONCLUSION: Hepatitis C can be
      successfully treated with IFN therapy, and the risk of IFN-induced psychosis is
      low, with psychotic symptoms resolving in most cases after completion of IFN
      therapy with or without antipsychotic treatment. In prolonged psychosis induced
      by IFN, quetiapine might also be of benefit.

PMID- 19855042
TI  - Neuropsychiatric systemic lupus erythematosus presenting as bipolar I disorder
      with catatonic features.
AB  - BACKGROUND: The American College of Rheumatology has defined 19 neuropsychiatric
      syndromes associated with systemic lupus erythematosus (SLE) involving the
      central, peripheral, and autonomic nervous systems. Neuropsychiatric
      manifestations of lupus (NPSLE) have been shown to occur in up to 95% of
      pediatric patients with SLE. OBJECTIVE: The authors describe a 15-year-old
      African American young woman with a family history positive for bipolar I
      disorder and schizophrenia, who presented with symptoms consistent with an
      affective disorder. METHOD: The patient was diagnosed with Bipolar I disorder
      with catatonic features and required multiple hospitalizations for mood
      disturbance. Two years after her initial presentation, the patient was noted to
      have a malar rash and subsequently underwent a full rheumatologic work-up, which
      revealed cerebral vasculitis. RESULTS: NPSLE was diagnosed and, after treatment
      with steroids, the patient improved substantially and no longer required further
      psychiatric medication or therapy. CONCLUSION: Given the especially high
      prevalence of NPSLE in pediatric patients with lupus, it is important for
      clinicians to recognize that neuropsychiatric symptoms in an adolescent patient
      may indeed be the initial manifestations of SLE, as opposed to a primary
      affective disorder.

PMID- 19855043
TI  - Glucagonoma-associated neuropsychiatric and affective symptoms: diagnostic
      dilemmas raised by paraneoplastic phenomena.

PMID- 19855044
TI  - Monitoring ventricular repolarization with QTc interval during antipsychotic
      therapy in patients with ventricular conduction abnormalities.

PMID- 19855045
TI  - Quality indicators in consultation-liaison psychiatry.

PMID- 19855046
TI  - Using administrative data to identify mental illness: what approach is best?
AB  - The authors estimated the validity of algorithms for identification of mental
      health conditions (MHCs) in administrative data for the 133 068 diabetic patients
      who used Veterans Health Administration (VHA) nationally in 1998 and responded to
      the 1999 Large Health Survey of Veteran Enrollees. They compared various
      algorithms for identification of MHCs from International Classification of
      Diseases, 9th Revision (ICD-9) codes with self-reported depression, posttraumatic
      stress disorder, or schizophrenia from the survey. Positive predictive value
      (PPV) and negative predictive value (NPV) for identification of MHC varied by
      algorithm (0.65-0.86, 0.68-0.77, respectively). PPV was optimized by requiring >
      or =2 instances of MHC ICD-9 codes or by only accepting codes from mental health
      visits. NPV was optimized by supplementing VHA data with Medicare data. Findings
      inform efforts to identify MHC in quality improvement programs that assess health
      care disparities. When using administrative data in mental health studies,
      researchers should consider the nature of their research question in choosing
      algorithms for MHC identification.

PMID- 19855047
TI  - Protein phosphatases 2C regulate the activation of the Snf1-related kinase OST1
      by abscisic acid in Arabidopsis.
AB  - The plant hormone abscisic acid (ABA) orchestrates plant adaptive responses to a
      variety of stresses, including drought. This signaling pathway is regulated by
      reversible protein phosphorylation, and genetic evidence demonstrated that
      several related protein phosphatases 2C (PP2Cs) are negative regulators of this
      pathway in Arabidopsis thaliana. Here, we developed a protein phosphatase
      profiling strategy to define the substrate preferences of the HAB1 PP2C
      implicated in ABA signaling and used these data to screen for putative
      substrates. Interestingly, this analysis designated the activation loop of the
      ABA activated kinase OST1, related to Snf1 and AMPK kinases, as a putative HAB1
      substrate. We experimentally demonstrated that HAB1 dephosphorylates and
      deactivates OST1 in vitro. Furthermore, HAB1 and the related PP2Cs ABI1 and ABI2
      interact with OST1 in vivo, and mutations in the corresponding genes strongly
      affect OST1 activation by ABA. Our results provide evidence that PP2Cs are
      directly implicated in the ABA-dependent activation of OST1 and further suggest
      that the activation mechanism of AMPK/Snf1-related kinases through the inhibition
      of regulating PP2Cs is conserved from plants to human.

PMID- 19855048
TI  - Rin4 causes hybrid necrosis and race-specific resistance in an interspecific
      lettuce hybrid.
AB  - Some inter- and intraspecific crosses may result in reduced viability or
      sterility in the offspring, often due to genetic incompatibilities resulting from
      interactions between two or more loci. Hybrid necrosis is a postzygotic genetic
      incompatibility that is phenotypically manifested as necrotic lesions on the
      plant. We observed hybrid necrosis in interspecific lettuce (Lactuca sativa and
      Lactuca saligna) hybrids that correlated with resistance to downy mildew.
      Segregation analysis revealed a specific allelic combination at two interacting
      loci to be responsible. The allelic interaction had two consequences: (1) a
      quantitative temperature-dependent autoimmunity reaction leading to necrotic
      lesions, lethality, and quantitative resistance to an otherwise virulent race of
      Bremia lactucae; and (2) a qualitative temperature-independent race-specific
      resistance to an avirulent race of B. lactucae. We demonstrated by transient
      expression and silencing experiments that one of the two interacting genes was
      Rin4. In Arabidopsis thaliana, RIN4 is known to interact with multiple R gene
      products, and their interactions result in hypersensitive resistance to
      Pseudomonas syringae. Site-directed mutation studies on the necrosis-eliciting
      allele of Rin4 in lettuce showed that three residues were critical for hybrid
      necrosis.

PMID- 19855049
TI  - Arabidopsis decapping 5 is required for mRNA decapping, P-body formation, and
      translational repression during postembryonic development.
AB  - Eukaryotic processing bodies (P-bodies) are implicated in mRNA storage and mRNA
      decapping. We previously found that a decapping complex comprising Decapping 1
      (DCP1), DCP2, and Varicose in Arabidopsis thaliana is essential for postembryonic
      development, but the underlying mechanism is poorly understood. Here, we
      characterized Arabidopsis DCP5, a homolog of human RNA-associated protein 55, as
      an additional P-body constituent. DCP5 associates with DCP1 and DCP2 and is
      required for mRNA decapping in vivo. In spite of its association with DCP2, DCP5
      has no effect on DCP2 decapping activity in vitro, suggesting that the effect on
      decapping in vivo is indirect. In knockdown mutant dcp5-1, not only is mRNA
      decapping compromised, but the size of P-bodies is also significantly decreased.
      These results indicate that DCP5 is required for P-body formation, which likely
      facilitates efficient decapping. During wild-type seed germination, mRNAs
      encoding seed storage proteins (SSPs) are translationally repressed and degraded.
      By contrast, in dcp5-1, SSP mRNAs are translated, leading to accumulation of
      their products in germinated seedlings. In vitro experiments using wheat germ
      extracts confirmed that DCP5 is a translational repressor. Our results showed
      that DCP5 is required for translational repression and P-body formation and plays
      an indirect role in mRNA decapping.

PMID- 19855050
TI  - ARABIDOPSIS TRITHORAX-RELATED7 is required for methylation of lysine 4 of histone
      H3 and for transcriptional activation of FLOWERING LOCUS C.
AB  - In the winter-annual accessions of Arabidopsis thaliana, presence of an active
      allele of FRIGIDA (FRI) elevates expression of FLOWERING LOCUS C (FLC), a
      repressor of flowering, and thus confers a vernalization requirement. FLC
      activation by FRI involves methylation of Lys 4 of histone H3 (H3K4) at FLC
      chromatin. Many multicellular organisms that have been examined contain two
      classes of H3K4 methylases, a yeast (Saccharomyces cerevisiae) Set1 class and a
      class related to Drosophila melanogaster Trithorax. In this work, we demonstrate
      that ARABIDOPSIS TRITHORAX-RELATED7 (ATXR7), a putative Set1 class H3K4
      methylase, is required for proper FLC expression. The atxr7 mutation partially
      suppresses the delayed flowering of a FRI-containing line. The rapid flowering of
      atxr7 is associated with reduced FLC expression and is accompanied by decreased
      H3K4 methylation and increased H3K27 methylation at FLC. Thus, ATXR7 is required
      for the proper levels of these histone modifications that set the level of FLC
      expression to create a vernalization requirement in winter-annual accessions.
      Previously, it has been reported that lesions in ATX1, which encodes a Trithorax
      class H3K4 methylase, partially suppress the delayed flowering of winter-annual
      Arabidopsis. We show that the flowering phenotype of atx1 atxr7 double mutants is
      additive relative to those of single mutants. Therefore, both classes of H3K4
      methylases appear to be required for proper regulation of FLC expression.

PMID- 19855051
TI  - Cotranslational proteolysis dominates glutathione homeostasis to support proper
      growth and development.
AB  - The earliest proteolytic event affecting most proteins is the excision of the
      initiating Met (NME). This is an essential and ubiquitous cotranslational process
      tightly regulated in all eukaryotes. Currently, the effects of NME on unknown
      complex cellular networks and the ways in which its inhibition leads to
      developmental defects and cell growth arrest remain poorly understood. Here, we
      provide insight into the earliest molecular mechanisms associated with the
      inhibition of the NME process in Arabidopsis thaliana. We demonstrate that the
      developmental defects induced by NME inhibition are caused by an increase in
      cellular proteolytic activity, primarily induced by an increase in the number of
      proteins targeted for rapid degradation. This deregulation drives, through the
      increase of the free amino acids pool, a perturbation of the glutathione
      homeostasis, which corresponds to the earliest limiting, reversible step
      promoting the phenotype. We demonstrate that these effects are universally
      conserved and that the reestablishment of the appropriate glutathione status
      restores growth and proper development in various organisms. Finally, we describe
      a novel integrated model in which NME, protein N-alpha-acylation, proteolysis,
      and glutathione homeostasis operate in a sequentially regulated mechanism that
      directs both growth and development.

PMID- 19855052
TI  - The challenge of traditional Chinese medicines for allopathic practitioners.

PMID- 19855053
TI  - Is endogenous ouabain a physiological regulator of cardiovascular and renal
      function?

PMID- 19855054
TI  - Maternal glucocorticoid exposure alters tight junction protein expression in the
      brain of fetal sheep.
AB  - We examined the expression of tight junction (TJ) proteins in the cerebral
      cortex, cerebellum, and spinal cord of fetuses after maternal treatment with
      single and multiple courses of dexamethasone. Ewes received either single courses
      of four 6-mg dexamethasone or placebo injections every 12 h for 48 h between 104
      and 107 days or the same treatment once a week between 76-78 and 104-107 days of
      gestation. TJ protein expression was determined by Western immunoblot analysis on
      tissue harvested at 105-108 days of gestation. Blood-brain barrier permeability
      has been previously quantified with the blood-to-brain transfer constant (K(i))
      with alpha-aminoisobutyric acid (39). After a single course of dexamethasone,
      claudin-5 increased (P < 0.05) in the cerebral cortex, occludin and claudin-1
      increased in the cerebellum, and occludin increased in the spinal cord. After
      multiple dexamethasone courses, occludin and zonula occludens (ZO)-1 increased in
      the cerebral cortex, and occludin and claudin-1 increased in the cerebellum.
      Junctional adhesion molecule-A and ZO-2 expressions did not change. Linear
      regression comparing K(i) to TJ proteins showed inverse correlations with claudin
      1 and claudin-5 in the cerebral cortex after a single course and ZO-2 in the
      spinal cord after multiple courses and direct correlations with ZO-1 in the
      cerebellum and spinal cord after multiple courses. We conclude that maternal
      glucocorticoid treatment increases the expression of specific TJ proteins in
      vivo, patterns of TJ protein expression vary after exposure to single and
      multiple glucocorticoid courses, and decreases in blood-brain barrier
      permeability are associated with increases in claudin-1, claudin-5, and ZO-2
      expression and decreases in ZO-1 expression. In utero glucocorticoid exposure
      alters the molecular composition of the barrier and affects fetal blood-brain
      barrier function.

PMID- 19855055
TI  - Mechanisms of aortic valve calcification: the LDL-density-radius theory: a
      translation from cell signaling to physiology.
AB  - Recent epidemiologic studies have revealed the risk factors associated for
      vascular atherosclerosis, including the male sex, smoking, hypertension, and
      elevated serum cholesterol, similar to the risk factors associated with the
      development of AV stenosis. An increasing number of models of experimental
      hypercholesterolemia demonstrate features of atherosclerosis in the AV, which are
      similar to the early stages of vascular atherosclerotic lesions. Experimental and
      clinical studies demonstrate that the hypercholesterolemic AV develops an
      atherosclerotic lesion which is proliferative and expresses high levels of
      osteoblast bone markers which mineralize over time to form bone. Calcification,
      the end-stage process of the disease, is necessary to understand as a prognostic
      indicator in the modification of this cellular process before it is too late. In
      summary, these findings suggest that medical therapies may have a potential role
      in patients in the early stages of this disease process to slow the progression
      to severe aortic stenosis and to delay the timing of the need for surgery. The
      translation of these experimental studies to clinical practice will be important
      to understand the potential for medical therapy for this disease process.

PMID- 19855056
TI  - Mitochondrial-derived hydrogen peroxide inhibits relaxation of bovine coronary
      arterial smooth muscle to hypoxia through stimulation of ERK MAP kinase.
AB  - Mitochondrial reactive oxygen species (ROS) are potentially important in vascular
      oxygen-sensing mechanisms because hypoxia appears to be a stimulus for
      mitochondrial ROS generation; however, scavenging of endogenous ROS does not
      alter relaxation of endothelium-denuded bovine coronary arteries (BCA) to
      hypoxia. The purpose of this study was to investigate the influence of increasing
      mitochondrial ROS on the relaxation of BCA to hypoxia. Increasing mitochondrial
      superoxide with inhibitors of electron transport (10 microM rotenone and
      antimycin) and by opening mitochondrial ATP-dependent K+ channels with 100 microM
      diazoxide were observed in this study to attenuate relaxation of BCA
      precontracted with 30 mM KCl to hypoxia by 68-76% and 38%, respectively. This
      effect of rotenone is not prevented by inhibiting NADPH oxidase (Nox) activation
      or scavenging superoxide with Peg-SOD; however, it is reversed 85% and 26% by
      increasing the consumption of intracellular peroxide by 0.1 mM ebselen and 32.5
      U/ml Peg-catalase. Because inhibition of extracellular signal-regulated kinase
      (ERK) mitogen-activated protein (MAP) kinase (10 microM PD-98059), but not src
      kinase or rho kinase, also reverses the effects of rotenone by 69%, the peroxide
      elicited force-enhancing effects of ERK appear to be attenuating the response to
      hypoxia. Rotenone increased the phosphorylation of ERK (by 163%). Activation of
      ERK in BCA with 0.1 mM peroxide or endogenous peroxide generated by stimulating
      Nox2 with a stretch treatment or contraction with 100 nM U-46619 also attenuated
      relaxation to hypoxia. Thus coronary arterial relaxation to hypoxia may be
      attenuated by pathophysiological conditions associated with increased peroxide
      generation by mitochondria or other sources that stimulate ERK.

PMID- 19855057
TI  - Simultaneous variation of ventricular pacing site and timing with biventricular
      pacing in acute ventricular failure improves function by interventricular assist.
AB  - The goal of this work was to investigate the hemodynamic effects of simultaneous
      left ventricular (LV) pacing site (LVPS) and interventricular pacing delay (VVD)
      variation with biventricular pacing (BiVP) during acute LV failure.
      Simultaneously varying LVPS and VVD with BiVP has been shown to improve
      hemodynamics during acute right ventricular (RV) failure. However, effects during
      acute LV failure have not been reported. In six open-chest pigs, acute LV volume
      overload was induced by regurgitant flow via an aortic-LV conduit. Epicardial
      BiVP was implemented with right atrial and ventricular leads and a custom LV
      pacing array. Fifty-four LVPS-VVD combinations were tested in random order.
      Cardiac output was evaluated by aortic flow probe, ventricular systolic function
      by maximum rate of ventricular pressure change, and mechanical interventricular
      synchrony by normalized RV-LV pressure diagram area. Simultaneous LVPS-VVD
      variation improved all measures of cardiac function. The observed effect was
      different for each functional index, with evidence of LVPS-VVD interaction.
      Compared with effects of LVPS-VVD variation in a model of acute RV failure,
      hemodynamic changes were markedly different. However, in both models, maximum
      rate of ventricular pressure change of the failing ventricle was improved with
      synchronous interventricular contraction, suggesting that, in acute ventricular
      failure, BiVP can recruit the unstressed ventricle to support systolic function
      of the failing one. Thus simultaneously varying LVPS and VVD with BiVP during
      acute ventricular failure can improve cardiac function by "interventricular
      assist", with hemodynamic effects dependent on the type of failure. This supports
      the potential utility of temporary BiVP for the treatment of acute ventricular
      failure commonly seen after cardiac surgery.

PMID- 19855058
TI  - Glucose enhances expression of TRPC1 and calcium entry in endothelial cells.
AB  - Hyperglycemia is a major risk factor for endothelial dysfunction and vascular
      disease, and in the current study, the link to glucose-induced abnormal
      intracellular Ca(2+) (Ca(i)(2+)) homeostasis was explored in bovine aortic
      endothelial cells in high glucose (HG; 25 mmol/l) versus low glucose (LG; 5.5
      mmol/l; control). Transient receptor potential 1 (TRPC1) ion channel protein, but
      not TRPC3, TRPC4, or TRPC6 expression, was significantly increased in HG versus
      LG at 72 h. HG for 4, 24, and 72 h did not change basal Ca(i)(2+) or ATP-induced
      Ca(i)(2+) release; however, the amplitude of sustained Ca(i)(2+) was
      significantly increased at 24 and 72 h and reduced by low concentration of the
      putative, but nonspecific, TRPC blockers, gadolinium, SKF-96365, and 2
      aminoethoxydiphenyl borate. Treatment with TRPC1 antisense significantly reduced
      TRPC1 protein expression and ATP-induced Ca(2+) entry in bovine aortic
      endothelial cells. Although the link between HG-induced changes in TRPC1
      expression, enhanced Ca(2+) entry, and endothelial dysfunction require further
      study, the current data are suggestive that targeting these pathways may reduce
      the impact of HG on endothelial function.

PMID- 19855059
TI  - Organization and collateralization of a subendocardial plexus in end-stage human
      heart failure.
AB  - In the failing myocardium a subendocardial plexus can develop. Detection of the
      presence or function, however, of such a plexus does not form part of the present
      diagnostic spectrum for heart failure. This may now change as new methods for
      high-resolution imaging of myocardial perfusion distribution are being developed.
      A severely hypertrophic heart was harvested during transplantation and analyzed
      for morphology of the intramural coronary arterial vasculature. The heart only
      had one coronary ostium, and the main branches of the coronary artery were
      cannulated. A fluorescent casting material was infused that was allowed to harden
      under physiological pressure. The entire heart was frozen and placed in a novel
      imaging cryomicrotome and sequentially cut in 25-microm slices. High-resolution
      images of each cutting plane were acquired, allowing a detailed three-dimensional
      reconstruction of the arterial vasculature. The epicardial layer of the free wall
      demonstrated a normal vasculature with penetrating branching arteries. The
      endocardial layer and the septum revealed a highly interconnected vascular plexus
      with large vessels oriented parallel to the apicobasal axis. An extensive
      endocardial network with collaterals was detected, forming connections between
      the main epicardial branches. We conclude that an outward remodeling of
      transmural vessels did not prevent the generation and growth of subendocardial
      conduit arteries. The orientation and vascular volume in the plexus provides an
      opportunity for detection by novel techniques of MRI contrast imaging currently
      developed. Knowledge of the effect on perfusion studies is required to prevent a
      misinterpretation of subendocardial perfusion images in heart failure.

PMID- 19855060
TI  - Role of local production of endothelium-derived nitric oxide on cGMP signaling
      and S-nitrosylation.
AB  - Nitric oxide (NO), synthesized by endothelial nitric oxide synthase (eNOS),
      exerts control over vascular function via two distinct mechanisms, the activation
      of soluble guanylate cyclase (sGC)/cGMP-dependent signaling or through S
      nitrosylation of proteins with reactive thiols (S-nitrosylation). Previous
      studies in cultured endothelial cells revealed that eNOS targeted to the plasma
      membrane (PM) releases greater amounts of NO compared with Golgi tethered eNOS.
      However, the significance of eNOS localization to sGC-dependent or -independent
      signaling is not known. Here we show that PM-targeted eNOS, when expressed in
      human aortic endothelial cells (HAEC) and isolated blood vessels, increases
      sGC/cGMP signaling to a greater extent than Golgi-localized eNOS. The ability of
      local NO production to influence sGC-independent mechanisms was also tested by
      monitoring the secretion of Von Willebrand factor (vWF), which is tonically
      inhibited by the S-nitrosylation of N-ethylmaleimide sensitive factor (NSF). In
      eNOS "knockdown" HAECs, vWF secretion was attenuated to a greater degree by PM
      eNOS compared with a Golgi-restricted eNOS. Moreover, the PM-targeted eNOS
      induced greater S-nitrosylation of NSF vs. Golgi eNOS. To distinguish between the
      amount of NO generated and the intracellular location of synthesis, we expressed
      Golgi and PM-targeted calcium-insensitive forms of eNOS in HAEC. These
      constructs, which generate equal amounts of NO regardless of location, produced
      equivalent increases in cGMP in bioassays and equal inhibition of vWF secretion.
      We conclude that the greater functional effects of PM eNOS are due to the
      increased amount of NO produced rather than effects derived from the local
      synthesis of NO.

PMID- 19855061
TI  - A transatrial pericardial access: lead placement as proof of concept.
AB  - A safe, easy, and quick access into the pericardial space may provide a window
      for diagnostics and therapeutics to the heart. The objective of this study was to
      provide proof of concept for an engagement and access catheter that allows access
      to the pericardial space percutaneously. A multilumen catheter was developed to
      allow navigation and suction fixation to the right atrial appendage/wall in a
      normal swine model. Advancement through the multilumen catheter using a second
      catheter with a distal needle tip allows access to the pericardial space without
      pericardial puncture and advancement of a standard guide wire into the space.
      Navigation into the pericardial space was undertaken by fluoroscopy alone and was
      accomplished in 10 swine (5 acute and 5 chronic). As a specific application of
      this pericardial access method, a pacing lead was implanted on the epicardial
      surface. Five chronic swine experiments were conducted with successful pacing
      engagement verified by lead impedance and pacing threshold and sensing. Lead
      impedance exceeded 1,000 Omega preengagement and dropped by an average of 200
      Omega upon implant (769 +/- 498 Omega). Pacing thresholds at 0.4 ms ranged from
      approximately 0.5 to 2.1 V acutely (1.03 +/- 0.92 V). No cardiac effusion or
      tamponade was observed in any of the acute or chronic studies. The ability to
      engage, maintain, and retract the right atrial appendage/wall and to engage an
      epicardial lead was successfully demonstrated. These findings support the
      feasibility of safe access into the pericardial space in a normal swine model and
      warrant further investigations for clinical translation.

PMID- 19855062
TI  - A mathematical model of vasoreactivity in rat mesenteric arterioles. II.
      Conducted vasoreactivity.
AB  - This study presents a multicellular computational model of a rat mesenteric
      arteriole to investigate the signal transduction mechanisms involved in the
      generation of conducted vasoreactivity. The model comprises detailed descriptions
      of endothelial (ECs) and smooth muscle (SM) cells (SMCs), coupled by nonselective
      gap junctions. With strong myoendothelial coupling, local agonist stimulation of
      the EC or SM layer causes local changes in membrane potential (V(m)) that are
      conducted electrotonically, primarily through the endothelium. When
      myoendothelial coupling is weak, signals initiated in the SM conduct poorly, but
      the sensitivity of the SMCs to current injection and agonist stimulation
      increases. Thus physiological transmembrane currents can induce different levels
      of local V(m) change, depending on cell's gap junction connectivity. The
      physiological relevance of current and voltage clamp stimulations in intact
      vessels is discussed. Focal agonist stimulation of the endothelium reduces
      cytosolic calcium (intracellular Ca(2+) concentration) in the prestimulated SM
      layer. This SMC Ca(2+) reduction is attributed to a spread of EC
      hyperpolarization via gap junctions. Inositol (1,4,5)-trisphosphate, but not
      Ca(2+), diffusion through homocellular gap junctions can increase intracellular
      Ca(2+) concentration in neighboring ECs. The small endothelial Ca(2+) spread can
      amplify the total current generated at the local site by the ECs and through the
      nitric oxide pathway, by the SMCs, and thus reduces the number of stimulated
      cells required to induce distant responses. The distance of the electrotonic and
      Ca(2+) spread depends on the magnitude of SM prestimulation and the number of SM
      layers. Model results are consistent with experimental data for vasoreactivity in
      rat mesenteric resistance arteries.

PMID- 19855063
TI  - Cardioprotection leads to novel changes in the mitochondrial proteome.
AB  - It is proposed that ischemic preconditioning (PC) initiates signaling that
      converges on mitochondria and results in cardioprotection. The outcome of this
      signaling on mitochondrial enzyme complexes is yet to be understood. We therefore
      used proteomic methods to test the hypothesis that PC and pharmacological
      preconditioning similarly alter mitochondrial signaling complexes. Langendorff
      perfused murine hearts were treated with the specific GSK-3 inhibitor AR-A014418
      (GSK Inhib VIII) for 10 min or subjected to four cycles of 5-min ischemia
      reperfusion (PC) before 20-min global ischemia and 120-min reperfusion. PC and
      GSK Inhib VIII both improved recovery of postischemic left ventricular developed
      pressure, decreased infarct size, and reduced lactate production during ischemia
      compared with their time-matched controls. We used proteomics to examine
      mitochondrial protein levels/posttranslational modifications that were common
      between PC and GSK Inhib VIII. Levels of cytochrome-c oxidase subunits Va and
      VIb, ATP synthase-coupling factor 6, and cytochrome b-c1 complex subunit 6 were
      increased while cytochrome c was decreased with PC and GSK Inhib VIII.
      Furthermore, the amount of cytochrome-c oxidase subunit VIb was found to be
      increased in PC and GSK Inhib VIII mitochondrial supercomplexes, which are
      comprised of complexes I, III, and IV. This result would suggest that changes in
      complex subunits associated with cardioprotection may affect supercomplex
      composition. Thus the ability of PC and GSK inhibition to alter the expression
      levels of electron transport complexes will have important implications for
      mitochondrial function.

PMID- 19855064
TI  - Stress-induced senescence exaggerates postinjury neointimal formation in the old
      vasculature.
AB  - This study aims to demonstrate the role of stress-induced senescence in aged
      related neointimal formation. We demonstrated that aging increases senescence
      associated beta-galactosidase activity (SA-beta-Gal) after vascular injury and
      the subsequent neointimal formation (neointima-to-media ratio: 0.8 +/- 0.2 vs.
      0.54 +/- 0.15) in rats. We found that senescent cells (SA-beta-Gal(+) p21(+))
      were scattered throughout the media and adventitia of the vascular wall at day 7
      after injury and reached their maximum number at day 14. However, senescent cells
      only persisted in the injured arteries of aged animals until day 30. No senescent
      cells were observed in the noninjured, contralateral artery. Interestingly,
      vascular senescent cells accumulated genomic 8-oxo-7,8-dihydrodeoxyguanine,
      indicating that these cells were under intense oxidative stress. To demonstrate
      whether senescence worsens intimal hyperplasia after injury, we seeded matrigel
      embedded senescent and nonsenescent vascular smooth muscle cells around injured
      vessels. The neointima was thicker in arteries treated with senescent cells with
      respect to those that received normal cells (neointima-to-media ratio: 0.41 +/-
      0.105 vs. 0.26 +/- 0.04). In conclusion, these results demonstrate that vascular
      senescence is not only a consequence of postinjury oxidative stress but is also a
      worsening factor for neointimal development in the aging vasculature.

PMID- 19855065
TI  - Improving insulin sensitivity via activation of PPAR-gamma increases telomerase
      activity in the heart of OLETF rats.
AB  - This study was conducted to examine telomere biology in terms of improving
      insulin sensitivity in a type 2 diabetic animal model: Otsuka Long-Evans
      Tokushima fatty (OLETF) rats. To improve insulin sensitivity, pioglitazone (PG;
      10 mg.kg(-1).day(-1)) was administrated to OLETF rats from 20 to 40 wk of age,
      and the effects of treatment were compared with those in untreated OLETF or
      control Long-Evans Tokushima Otsuka fatty rats. At the end of the study, the
      homeostasis model assessment of insulin resistance significantly increased in
      OLETF rats but decreased in OLETF rats treated with PG. No shortening of telomere
      length was observed in the heart tissue of OLETF rats, whereas telomerase
      activity was decreased in OLETF heart tissue. The mRNA expression of both
      telomerase reverse transcriptase and telomere repeat binding factor 2 was
      downregulated in the hearts of OLETF rats. The protein expression of phospho-Akt,
      insulin-like growth factor, and endothelial nitric oxide synthase was reduced in
      OLETF rats. On the other hand, myocardial matrix metalloproteinase-9 expression
      was elevated in OLETF rats. The changes observed in OLETF rats were inhibited by
      PG treatment. However, protein and mRNA expression of Sirt1, a lifespan
      modulator, were attenuated in OLETF rat hearts, although they were enhanced in
      OLETF rats with PG treatment. Myocardial fibrosis was less extensive and
      diastolic dysfunction more greatly ameliorated in PG-treated OLETF rats than in
      OLETF rats. These findings suggest that improving insulin sensitivity via the
      activation of peroxisom proliferator-activated receptor-gamma may exert
      regulatory effects on cardiac telomere biology and may have desirable
      morphological and functional effects on the diabetic heart.

PMID- 19855067
TI  - Beta-adrenergic modulation of arrhythmogenesis and identification of targeted
      sites of antiarrhythmic therapy in Timothy (LQT8) syndrome: a theoretical study.
AB  - Timothy syndrome (TS) is a malignant form of congenital long QT syndrome with a
      mode of arrhythmia onset often triggered by enhanced sympathetic tone. We sought
      to explore mechanisms by which beta-adrenergic stimulation (BAS) modulates
      arrhythmogenesis and to identify potential targeted sites of antiarrhythmic
      therapy in TS. Using a dynamic Luo-Rudy ventricular myocyte model incorporated
      with detailed intracellular Ca(2+) cycling, along with its one-dimensional
      multicellular strand, we simulated various clinical scenarios of TS, with
      stepwise increase in the percentage of G406R Ca(v)1.2 channels from 0 to 11.5 and
      23%, and to 38.5 and 77%, respectively, for heterozygous and homozygous states of
      TS1 and TS2. Progressive prolongation of action potential duration (APD) and QT
      interval, accompanied by amplification of transmural dispersion of
      repolarization, steepening of APD restitution, induction of delayed
      afterdepolariztions (DADs), and both DAD and phase 3 early afterdepolariztion
      mediated triggered activities, correlated well with the extent of G406R Ca(v)1.2
      channel mutation. BAS amplified transmural dispersion of repolarization,
      steepened APD restitution, and facilitated inducibility of DAD-mediated triggered
      activity. Systematic analysis of intracellular Ca(2+) cycling revealed that
      sarcoplasmic reticulum Ca(2+) ATPase (uptake current) played an essential role in
      BAS-induced facilitation of DAD-mediated triggered activity and, in addition to L
      type calcium current, it could be an effective site of antiarrhythmic therapy
      under the influence of BAS. Thus G406R Ca(v)1.2 channel mutation confers not only
      a trigger, but also a substrate for lethal ventricular arrhythmias, which can be
      exaggerated by BAS. It is suggested that, besides beta-adrenergic blockers and L
      type calcium current channel blockers, an agent aimed at reduction of
      sarcoplasmic reticulum Ca(2+) ATPase uptake current may provide additional
      antiarrhythmic effect in patients with TS.

PMID- 19855066
TI  - Nonanticoagulant heparin reduces myocyte Na+ and Ca2+ loading during simulated
      ischemia and decreases reperfusion injury.
AB  - Heparin desulfated at the 2-O and 3-O positions (ODSH) decreases canine
      myocardial reperfusion injury. We hypothesized that this occurs from effects on
      ion channels rather than solely from anti-inflammatory activities, as previously
      proposed. We studied closed-chest pigs with balloon left anterior descending
      coronary artery occlusion (75-min) and reperfusion (3-h). ODSH effects on
      [Na(+)](i) (Na Green) and [Ca(2+)](i) (Fluo-3) were measured by flow cytometry in
      rabbit ventricular myocytes after 45-min of simulated ischemia [metabolic
      inhibition with 2 mM cyanide, 0 glucose, 37 degrees C, pacing at 0.5 Hz; i.e.,
      pacing-metabolic inhibition (PMI)]. Na(+)/Ca(2+) exchange (NCX) activity and
      Na(+) channel function were assessed by voltage clamping. ODSH (15 mg/kg) 5 min
      before reperfusion significantly decreased myocardial necrosis, but neutrophil
      influx into reperfused myocardium was not consistently reduced. ODSH (100
      microg/ml) reduced [Na(+)](i) and [Ca(2+)](i) during PMI. The NCX inhibitor KB
      R7943 (10 microM) or the late Na(+) current (I(Na-L)) inhibitor ranolazine (10
      microM) reduced [Ca(2+)](i) during PMI and prevented effects of ODSH on Ca(2+)
      loading. ODSH also reduced the increase in Na(+) loading in paced myocytes caused
      by 10 nM sea anemone toxin II, a selective activator of I(Na-L). ODSH directly
      stimulated NCX and reduced I(Na-L). These results suggest that in the intact
      heart ODSH reduces Na(+) influx during early reperfusion, when I(Na-L) is
      activated by a burst of reactive oxygen production. This reduces Na(+) overload
      and thus Ca(2+) influx via NCX. Stimulation of Ca(2+) extrusion via NCX later
      after reperfusion may also reduce myocyte Ca(2+) loading and decrease infarct
      size.

PMID- 19855068
TI  - Increased death receptor pathway of apoptotic signaling in septic mouse aorta:
      effect of systemic delivery of FADD siRNA.
AB  - Recent evidence suggests that apoptotic cell death plays an important role in the
      pathophysiology of sepsis. Because there is extensive apoptosis of vascular
      endothelial cells in sepsis, we examined whether the death receptor pathway of
      apoptotic signaling is altered in thoracic aortas from mice with polymicrobial
      sepsis, as produced by cecal ligation and puncture (CLP). In septic aorta, total
      and surface expression levels of the two death receptors tumor necrosis factor
      receptor 1 and Fas were highly upregulated. Furthermore, marked increases in the
      mRNA and protein levels of Fas-associated death domain (FADD), an adaptor
      molecule to recruit procaspase-8 into the death-inducing signal complex, were
      observed in septic aorta, which were strongly suppressed by systemic delivery of
      small interfering RNA (siRNA) against FADD. No increase in expression of death
      receptors and FADD was observed in endothelium-denuded aortic tissues from septic
      animals. Systemic administration of FADD siRNA also resulted in great attenuation
      of sepsis-induced increases in expression and activation of caspase-3, an
      effector protease in the apoptosis cascade. Terminal deoxynucleotidyl transferase
      dUTP-mediated nick-end labeling (TUNEL) revealed that the significant appearance
      of cell apoptosis in aortic endothelium after CLP-induced sepsis was eliminated
      when FADD siRNA was systemically applied. Light and electron microscopic
      examinations of septic aorta showed cell swelling, nuclear fragmentation, and
      partial detachment of endothelial cells from the basal membrane, which were
      prevented by systemic treatment with FADD siRNA. Finally, FADD siRNA
      administration dramatically improved survival of CLP mice, supporting the
      feasibility of this gene-based approach for treating septic shock.

PMID- 19855070
TI  - Blood glutathione peroxidase-1 mRNA levels can be used as molecular biomarkers to
      determine dietary selenium requirements in rats.
AB  - Transcript (mRNA) levels are increasingly being used in medicine as molecular
      biomarkers for disease and disease risk, including use of whole blood as a target
      tissue for analysis. Development of blood molecular biomarkers for nutritional
      status, too, has potential application that parallels opportunities in medicine,
      including providing solid data for individualized nutrition. We previously
      reported that blood glutathione peroxidase-1 (Gpx1) mRNA was expressed at levels
      comparable to major tissues in rats and humans. To determine the efficacy of
      using blood Gpx1 mRNA to assess selenium (Se) status and requirements, we fed
      graded levels of Se (0-0.3 microg Se/g as selenite) to weanling male rats. Se
      status was determined by liver Se concentration and selenoenzyme activity, and
      selenoprotein mRNA abundance in liver and blood was determined by ribonuclease
      protection analysis. Liver Se and plasma glutathione peroxidase-3 and liver Gpx1
      activities indicated that minimal Se requirements were at 0.08 microg Se/g diet.
      When total RNA was isolated from whole blood, Gpx1 mRNA in Se-deficient rats
      decreased to 10% of levels in Se-adequate (0.2 microg Se/g diet) rats. With Se
      supplementation, blood Gpx1 mRNA levels increased sigmoidally to a plateau with a
      minimum Se requirement of 0.08 microg Se/g diet, whereas glutathione peroxidase-4
      mRNA levels were unaffected. Similarly, Gpx1 mRNA in RNA isolated from
      fractionated red blood cells decreased in Se-deficient rats to 23% of Se-adequate
      levels, with a minimum Se requirement of 0.09 microg Se/g diet. Additional
      studies showed that the preponderance of whole blood Gpx1 mRNA arises from
      erythroid cells, most likely reticulocytes and young erythrocytes. In summary,
      whole blood selenoprotein mRNA levels can be used as molecular biomarkers for
      assessing Se requirements, illustrating that whole blood has potential as a
      target tissue in development of molecular biomarkers for use in nutrition as well
      as in medicine.

PMID- 19855071
TI  - High fat and highly thermolyzed fat diets promote insulin resistance and increase
      DNA damage in rats.
AB  - Many studies have demonstrated that DNA damage may be associated with type 2
      diabetes mellitus (T2DM) and its complications. The goal of this study was to
      evaluate the effects of the potential relationship between fat (thermolyzed)
      intake, glucose dyshomeostasis and DNA injury in rats. Biochemical parameters
      related to glucose metabolism (i.e., blood glucose levels, insulin tolerance
      tests, glucose tolerance tests and fat cell glucose oxidation) and general health
      parameters (i.e., body weight, retroperitoneal and epididymal adipose tissue)
      were evaluated in rats after a 12-month treatment with either a high fat or a
      high thermolyzed fat diet. The high fat diet (HFD) and high fat thermolyzed diet
      (HFTD) showed increased body weight and impaired insulin sensitivity at the
      studied time-points in insulin tolerance test (ITT) and glucose tolerance test
      (GTT). Interestingly, only animals subjected to the HFTD diet showed decreased
      epididymal fat cell glucose oxidation. We show which high fat diets have the
      capacity to reduce glycogen synthesis by direct and indirect pathways. HFTD
      promoted an increase in lipid peroxidation in the liver, demonstrating
      significant damage in lipids in relation to other groups. Blood and hippocampus
      DNA damage was significantly higher in animals subjected to HFDs, and the highest
      damage was observed in animals from the HFTD group. Striatum DNA damage was
      significantly higher in animals subjected to HFDs, compared with the control
      group. These results show a positive correlation between high fat diet, glucose
      dyshomeostasis, oxidative stress and DNA damage.

PMID- 19855072
TI  - The cellular and molecular immune response of the weanling piglet to
      staphylococcal enterotoxin B.
AB  - Staphylococcal enterotoxin B (SEB) is a biothreat agent, etiologic agent of food
      poisoning, and potent inducer of toxic shock syndrome. This heat-stable
      exoprotein is thought to act as a superantigen to induce T cell-specific
      pathology. Most animal models do not accurately map the clinical syndrome of
      human SEB exposure. Previously, we have demonstrated the utility of the weanling
      piglet model of SEB intoxication. Here, we analyze gross and histopathologic
      specimens from lymphoid tissue of these animals. Hematological testing was
      completed to observe changes in circulating leukocytes. Further, these leukocytes
      were differentiated and the subsets were subsequently analyzed using flow
      cytometry. Cytokine mRNA was quantified in lymphoid tissue and peripheral blood
      cells and compared to actual protein concentration using ELISA. The mRNA
      expression levels for several cell markers implicated in T and B cell
      differentiation were quantified and compared to control animals, as were levels
      for apoptosis-related genes. Lymphadenopathy was constantly seen post mortem. SEB
      exposed animals had a leukocytosis which increased linearly over the time course.
      Monocyte levels increased over time, while lymphocyte levels peaked at 6h and
      then returned to baseline. Most cytokines had mRNA levels that were upregulated
      after exposure. Detection of serum cytokine changes was accomplished; however,
      these patterns did not always follow those seen in the differentially expressed
      genes. Both pro- and anti-apoptotic genes were differentially expressed in
      exposed animals. This paper reports, for the first time, the immunological
      findings in the weanling piglet model of SEB intoxication. From this work it is
      clear that there is not one absolute cell-mediated pathway contributing to the
      pathology these animals exhibit as a result of SEB exposure.

PMID- 19855073
TI  - The IL-8 production by Streptococcal pyrogenic exotoxin B.
AB  - We have previously identified alpha(v)beta(3) and Fas as receptors for the
      streptococcal pyrogenic exotoxin B (SPE B), and G308S, a mutant of SPE B with RSD
      motif, which interacts with Fas only. This study aims to evaluate how SPE B
      interacts with cells to induce the production of IL-8. Our results showed that
      following exposure to SPE B or G308S, the levels of IL-8 protein and mRNA were
      increased and the increase was inhibited by the addition of anti-Fas antibody,
      suggesting that the increased production of IL-8 by SPE B is mediated through Fas
      receptor. In the presence of G308S, the association of FADD and procaspase 8, and
      activation of NF-kappaB were also detected. The application of siRNA of FADD and
      of procaspase 8 could inhibit the NF-kappaB activity. The proteolytic activity of
      caspase 8 was required for the NF-kappaB activity. Further studies showed that
      G308S could increase the phosphorylation of ERK and the translocation of NF
      kappaB into the nucleus, and the inhibition of ERK phosphorylation decreased the
      IL-8 production, mRNA expression and activation of NF-kappaB. In addition, siRNA
      of procaspase 8 could inhibit the G308S-induced cleavage of MEKK1, binding of
      MEKK1 to caspase 8, activation of ERK and the NF-kappaB activity. Taken together,
      the production of IL-8 by SPE B in A549 cells is mediated by Fas, and followed by
      the activation of FADD, caspase 8, MEKK1, ERK and NF-kappaB.

PMID- 19855074
TI  - NF-kappaB independent activation of a series of proinflammatory genes by hydrogen
      sulfide.
AB  - A stress response has the potential to induce greater resistance to subsequent
      stress damage. We tested whether hydrogen sulfide (H(2)S), an important signaling
      molecule, also used therapeutically, and known for detrimental effects, might
      induce a protective stress response. Therefore, the response of fibroblast-like
      synoviocytes (FLS) treated with sodium hydrosulfide and mice exposed to H(2)S
      were examined. In both cases a profound and long lasting induction of the stress
      response could be detected. However, despite the sustained presence of large
      levels of HO-1 and HSP-70, proinflammatory effects of exposure to IL-1beta or
      H(2)S itself were not ameliorated. On the contrary, at H(2)S concentrations
      significantly lower than 10 ppm-the current maximal allowable concentration of
      H(2)S in many countries-COX-2, IL-8, IL-1alpha, IL-1beta and TNFalpha were dose
      dependently elevated. Importantly, in FLS, short-term exposure to H(2)S resulted
      in the activation of all three MAPK. In addition, mitochondrial activity was also
      significantly impaired at relatively low H(2)S concentrations. The transcription
      factor NF-kappaB is essential for the activation of most proinflammatory genes.
      However, the data presented imply that H(2)S activates proinflammatory genes in
      FLS through non-NF-kappaB-dependent pathways. Stress proteins reportedly act by
      blocking NF-kappaB activation, a mechanism that would explain the inability of
      stress proteins to prevent H(2)S mediated inflammatory processes. The presented
      data, showing MAPK activation, NF-kappaB-independent activation of a number of
      proinflammatory genes and mitochondrial damage, help to provide a better
      understanding of the biological and pathophysiological effects of exposure to
      H(2)S.

PMID- 19855075
TI  - Endogenous opioids regulate expression of experimental autoimmune
      encephalomyelitis: a new paradigm for the treatment of multiple sclerosis.
AB  - Preclinical investigations utilizing murine experimental auto-immune
      encephalomyelitis (EAE), as well as clinical observations in patients with
      multiple sclerosis (MS), may suggest alteration of endogenous opioid systems in
      MS. In this study we used the opioid antagonist naltrexone (NTX) to invoke a
      continuous (High Dose NTX, HDN) or intermittent (Low Dose NTX, LDN) opioid
      receptor blockade in order to elucidate the role of native opioid peptides in
      EAE. A mouse model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE was
      employed in conjunction with daily treatment of LDN (0.1 mg/kg, NTX), HDN (10
      mg/kg NTX), or vehicle (saline). No differences in neurological status
      (incidence, severity, disease index), or neuropathological assessment (activated
      astrocytes, demyelination, neuronal injury), were noted between MOG-induced mice
      receiving HDN or vehicle. Over 33% of the MOG-treated animals receiving LDN did
      not exhibit behavioral signs of disease, and the severity and disease index of
      the LDN-treated mice were markedly reduced from cohorts injected with vehicle.
      Although all LDN animals demonstrated neuropathological signs of EAE, LDN-treated
      mice without behavioral signs of disease had markedly lower levels of activated
      astrocytes and demyelination than LDN- or vehicle-treated animals with disease.
      These results imply that endogenous opioids, evoked by treatment with LDN and
      acting in the rebound period from drug exposure, are inhibitory to the onset and
      progression of EAE, and suggest that clinical studies of LDN are merited in MS
      and possibly in other autoimmune disorders.

PMID- 19855076
TI  - Segmental muscle vibration improves walking in chronic stroke patients with foot
      drop: a randomized controlled trial.
AB  - BACKGROUND: Studies have described the effects of segmental muscle vibration
      (SMV) on brain plasticity and corticomotor excitability. Information on the
      treatment-induced effects of SMV in stroke patients is, however, still limited.
      OBJECTIVES: To assess whether the application of SMV to ankle dorsiflexor muscles
      of chronic stroke patients can improve walking. METHODS: Forty-four patients were
      randomly assigned to either an experimental group (EG) or a control group (CG)
      and underwent 12 sessions over 4 weeks of general physical therapy. Patients in
      the EG also received SMV at 120 Hz over the peroneus longus and tibialis anterior
      for 30 minutes at the end of each session. All the participants underwent
      pretreatment and posttreatment gait analysis assessments. Time-distance,
      kinematic, and surface electromyography (EMG) data were used as outcome measures.
      RESULTS: A moderate improvement in mean gait speed, normal-side swing velocity,
      bilateral stride length, and normal-side toe-off percentage was observed only in
      the EG. A significant increase in bilateral ankle dorsiflexion angle at heel
      contact was associated with increased maximum ankle dorsiflexion and
      plantarflexion degrees during the swing phase on the paretic side after treatment
      in EG. Surface EMG during the swing phase revealed a significant increase in the
      activation of the tibialis anterior muscle on the paretic side in the
      posttreatment assessment in the EG. CONCLUSIONS: SMV added to general physical
      therapy may improve gait performance in patients with foot drop secondary to
      chronic stroke. The authors hypothesize that this may be due to the mechanical
      vibration stimulation, probably as a consequence of effective brain
      reorganization.

PMID- 19855077
TI  - A perspective on challenges and issues in biomarker development and drug and
      biomarker codevelopment.
AB  - A workshop sponsored by the National Cancer Institute and the US Food and Drug
      Administration addressed past lessons learned and ongoing challenges faced in
      biomarker development and drug and biomarker codevelopment. Participants agreed
      that critical decision points in the product life cycle depend on the level of
      understanding of the biology of the target and its interaction with the drug, the
      preanalytical and analytical factors affecting biomarker assay performance, and
      the clinical disease process. The more known about the biology and the greater
      the strength of association between an analytical signal and clinical result, the
      more efficient and less risky the development process will be. Rapid entry into
      clinical practice will only be achieved by using a rigorous scientific approach,
      including careful specimen collection and standardized and quality-controlled
      data collection. Early interaction with appropriate regulatory bodies will ensure
      studies are appropriately designed and biomarker test performance is well
      characterized.

PMID- 19855078
TI  - Specific promoter methylation identifies different subgroups of MLL-rearranged
      infant acute lymphoblastic leukemia, influences clinical outcome, and provides
      therapeutic options.
AB  - MLL-rearranged infant acute lymphoblastic leukemia (ALL) remains the most
      aggressive type of childhood leukemia, displaying a unique gene expression
      profile. Here we hypothesized that this characteristic gene expression signature
      may have been established by potentially reversible epigenetic modifications. To
      test this hypothesis, we used differential methylation hybridization to explore
      the DNA methylation patterns underlying MLL-rearranged ALL in infants. The
      obtained results were correlated with gene expression data to confirm gene
      silencing as a result of promoter hypermethylation. Distinct promoter CpG island
      methylation patterns separated different genetic subtypes of MLL-rearranged ALL
      in infants. MLL translocations t(4;11) and t(11;19) characterized extensively
      hypermethylated leukemias, whereas t(9;11)-positive infant ALL and infant ALL
      carrying wild-type MLL genes epigenetically resembled normal bone marrow.
      Furthermore, the degree of promoter hypermethylation among infant ALL patients
      carrying t(4;11) or t(11;19) appeared to influence relapse-free survival, with
      patients displaying accentuated methylation being at high relapse risk. Finally,
      we show that the demethylating agent zebularine reverses aberrant DNA methylation
      and effectively induces apoptosis in MLL-rearranged ALL cells. Collectively these
      data suggest that aberrant DNA methylation occurs in the majority of MLL
      rearranged infant ALL cases and guides clinical outcome. Therefore, inhibition of
      aberrant DNA methylation may be an important novel therapeutic strategy for MLL
      rearranged ALL in infants.

PMID- 19855080
TI  - Molecular and functional analysis of the stem cell compartment of chronic
      myelogenous leukemia reveals the presence of a CD34- cell population with
      intrinsic resistance to imatinib.
AB  - We show the molecular and functional characterization of a novel population of
      lineage-negative CD34-negative (Lin(-)CD34(-)) hematopoietic stem cells from
      chronic myelogenous leukemia (CML) patients at diagnosis. Molecular karyotyping
      and quantitative analysis of BCR-ABL transcript demonstrated that approximately
      one-third of CD34(-) cells are leukemic. CML Lin(-)CD34(-) cells showed kinetic
      quiescence and limited clonogenic capacity. However, stroma-dependent cultures
      induced CD34 expression on some cells and cell cycling, and increased clonogenic
      activity and expression of BCR-ABL transcript. Lin(-)CD34(-) cells showed
      hematopoietic cell engraftment rate in 2 immunodeficient mouse strains similar to
      Lin-CD34(+) cells, whereas endothelial cell engraftment was significantly higher.
      Gene expression profiling revealed the down-regulation of cell-cycle arrest genes
      and genes involved in antigen presentation and processing, while the expression
      of genes related to tumor progression, such as angiogenic factors, was strongly
      up-regulated compared with normal counterparts. Phenotypic analysis confirmed the
      significant down-regulation of HLA class I and II molecules in CML Lin(-)CD34(-)
      cells. Imatinib mesylate did not reduce fusion transcript levels, BCR-ABL kinase
      activity, and clonogenic efficiency of CML Lin(-)CD34(-) cells in vitro.
      Moreover, leukemic CD34(-) cells survived exposure to BCR-ABL inhibitors in vivo.
      Thus, we identified a novel CD34(-) leukemic stem cell subset in CML with
      peculiar molecular and functional characteristics.

PMID- 19855079
TI  - Comprehensive genomic screens identify a role for PLZF-RARalpha as a positive
      regulator of cell proliferation via direct regulation of c-MYC.
AB  - The t(11;17)(q23;q21) translocation is associated with a retinoic acid (RA)
      insensitive form of acute promyelocytic leukemia (APL), involving the production
      of reciprocal fusion proteins, promyelocytic leukemia zinc finger-retinoic acid
      receptor alpha (PLZF-RARalpha) and RARalpha-PLZF. Using a combination of
      chromatin immunoprecipitation promotor arrays (ChIP-chip) and gene expression
      profiling, we identify novel, direct target genes of PLZF-RARalpha that tend to
      be repressed in APL compared with other myeloid leukemias, supporting the role of
      PLZF-RARalpha as an aberrant repressor in APL. In primary murine hematopoietic
      progenitors, PLZF-RARalpha promotes cell growth, and represses Dusp6 and Cdkn2d,
      while inducing c-Myc expression, consistent with its role in leukemogenesis. PLZF
      RARalpha binds to a region of the c-MYC promoter overlapping a functional PLZF
      site and antagonizes PLZF-mediated repression, suggesting that PLZF-RARalpha may
      act as a dominant-negative version of PLZF by affecting the regulation of shared
      targets. RA induced the differentiation of PLZF-RARalpha-transformed murine
      hematopoietic cells and reduced the frequency of clonogenic progenitors,
      concomitant with c-Myc down-regulation. Surviving RA-treated cells retained the
      ability to be replated and this was associated with sustained c-Myc expression
      and repression of Dusp6, suggesting a role for these genes in maintaining a self
      renewal pathway triggered by PLZF-RARalpha.

PMID- 19855081
TI  - BCL6 modulates tonic BCR signaling in diffuse large B-cell lymphomas by
      repressing the SYK phosphatase, PTPROt.
AB  - Tonic B-cell receptor (BCR) signaling is a key survival pathway during normal B
      cell ontogenesis and in a subset of diffuse large B-cell lymphomas (DLBCLs). We
      previously demonstrated that BCR-dependent DLBCL cell lines and primary tumors
      underwent apoptosis after treatment with an ATP-competitive inhibitor of the BCR
      associated spleen tyrosine kinase (SYK). These "BCR-type" tumors also have more
      abundant expression of the transcriptional repressor, BCL6, and increased
      sensitivity to BCL6 inhibition. Herein, we evaluated potential connections
      between BCL6-mediated transcriptional repression and SYK-dependent BCR signaling.
      In transcriptionally profiled normal B-cell subsets (naive, germinal center, and
      memory B cells) and in primary DLBCLs, there were reciprocal patterns of
      expression of BCL6 and the SYK tyrosine phosphatase PTPROt. BCL6 repressed PTPROt
      transcription via a direct interaction with functional BCL6 binding sites in the
      PTPROt promoter. Enforced expression of BCL6 in normal naive B cells and RNAi
      mediated depletion of BCL6 in germinal center B cells directly modulated PTPROt
      expression. In "BCR-type" DLBCLs, BCL6 depletion increased PTPROt expression and
      decreased phosphorylation of SYK and the downstream adaptor protein BLNK. Because
      BCL6 augments BCR signaling and BCL6 and SYK are both promising therapeutic
      targets in many DLBCLs, combined inhibition of these functionally related
      pathways warrants further study.

PMID- 19855082
TI  - Immunoregulatory functions of KLRG1 cadherin interactions are dependent on
      forward and reverse signaling.
AB  - KLRG1 is an inhibitory receptor expressed on a subset of mature T and NK cells.
      Recently, E-, N-, and R-cadherin have been identified as ligands for KLRG1.
      Cadherins are a large family of transmembrane or membrane-associated
      glycoproteins that were thought to only bind specifically to other cadherins to
      mediate specific cell-to-cell adhesion in a Ca(2+)-dependent manner. The
      consequences of cadherin KLRG1 molecular interactions are not well characterized.
      Here, we report that the first 2 extracellular domains of cadherin are sufficient
      to initiate a KLRG1-dependent signaling. We also demonstrate that KLRG1
      engagement inhibits cadherin-dependent cellular adhesion and influences dendritic
      cell secretion of inflammatory cytokines, thereby exerting immunosuppressive
      effects. Consistent with this, engagement of cadherin by KLRG1 molecule induces
      cadherin tyrosine phosphorylation. Therefore, KLRG1/cadherin interaction leads to
      the generation of a bidirectional signal in which both KLRG1 and cadherin
      activate downstream signaling cascades simultaneously. Taken together, our
      results provide novel insights on how KLRG1 and E-cadherin interactions are
      integrated to differentially regulate not only KLRG1(+) cells, but also E
      cadherin-expressing cells, such as dendritic cells.

PMID- 19855083
TI  - Anticoagulant and antithrombotic properties of platelet protease nexin-1.
AB  - Protease nexin-1 (PN-1) is a serpin that inhibits plasminogen activators,
      plasmin, and thrombin. PN-1 is barely detectable in plasma but is expressed by
      platelets. Here, we studied platelet PN-1 in resting and activated conditions and
      its function in thrombosis. Studies on human platelets from healthy donors and
      from patients with a Gray platelet syndrome demonstrate that PN-1 is present both
      at the platelet surface and in alpha-granules. The role of PN-1 was investigated
      in vitro using human platelets incubated with a blocking antibody and using
      platelets from PN-1-deficient mice. Both approaches indicate that platelet PN-1
      is active on thrombin and urokinase-type plasminogen activator. Blockade and
      deficiency of platelet PN-1 result in accelerated and increased tissue factor
      induced thrombin generation as indicated by calibrated automated thrombography.
      Moreover, platelets from PN-1-deficient mice respond to subthreshold doses of
      thrombin, as assessed by P-selectin expression and platelet aggregation. Thrombus
      formation, induced ex vivo by collagen in blood flow conditions and in vivo by
      FeCl(3)-induced injury, is significantly increased in PN-1-deficient mice,
      demonstrating the antithrombotic properties of platelet PN-1. Platelet PN-1 is
      thus a key player in the thrombotic process, whose negative regulatory role has
      been, up to now, markedly underestimated.

PMID- 19855084
TI  - Epicatechin gallate suppresses oxidative stress-induced MUC5AC overexpression by
      interaction with epidermal growth factor receptor.
AB  - The goal of this study was to investigate the effect of epicatechin gallate
      (ECG), a component of green tea polyphenols, on the signal pathway for oxidative
      stress-induced intracellular reactive oxygen species (ROS) generation and MUC5AC
      overexpression in normal human nasal epithelial (NHNE) cells. Passage-2 NHNE
      cells were used, and ECG was administered before stimulation with exogenous
      hydrogen peroxide (H(2)O(2)). MUC5AC gene and protein levels were measured by
      real-time PCR and dot blot analysis. Western blot analysis and
      immunocytofluorescence study were performed for detecting the activity of
      epidermal growth factor receptor (EGFR). Exogenous H(2)O(2) increases
      intracellular ROS generation, leading to the overexpression of MUC5AC. The
      phosphorylation and internalization of EGFR were associated with this ROS
      generation. ECG decreased the phosphorylation and internalization of EGFR at the
      cell surface of NHNE cells, resulting in the attenuation of exogenous H(2)O(2)
      induced intracellular ROS generation and MUC5AC overexpression. ECG may be a
      therapeutic material against oxidative stress-induced ROS generation and mucus
      hypersecretion in airways.

PMID- 19855085
TI  - Multiple mechanisms influence regulation of the cystic fibrosis transmembrane
      conductance regulator gene promoter.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) gene is driven by
      a promoter that cannot alone account for the temporal and tissue-specific
      regulation of the gene. This has led to the search for additional regulatory
      elements that cooperate with the basal promoter to achieve coordinated
      expression. We previously identified two alternative upstream exons of the gene
      that were mutually exclusive of the first exon, and one of which showed temporal
      regulation in the human and sheep lung. We now demonstrate that this alternative
      splice product generates a stable protein, which initiates translation at an ATG
      in exon 4, and thus lacks the N terminus of CFTR. The other splice variant
      inhibits translation of the protein. In a search for the promoter used by the
      upstream exons, we identified a novel element that contributes to the activity of
      the basal CFTR promoter in airway epithelial cells, but does not function
      independently. Finally, we demonstrate that, in primary airway cells, skin
      fibroblasts, and both airway and intestinal cell lines, the CFTR promoter is
      unmethylated, irrespective of CFTR expression status. Thus, methylation is not
      the main cause of inactivation of CFTR transcription.

PMID- 19855086
TI  - Post-transcriptional regulation of plasminogen activator inhibitor type-1
      expression in human pleural mesothelial cells.
AB  - The plasminogen activator inhibitor type-1 (PAI-1) effectively blocks the
      activities of free and receptor-bound urokinase-type plasminogen activator.
      Incubation of cultured human pleural mesothelial (Met5A) cells with TGF-beta
      increased PAI-1 protein. TGF-beta, phorbol myristate acetate, and the translation
      inhibitor cycloheximide induced PAI-1 mRNA and slowed its degradation, suggesting
      that PAI-1 mRNA could be regulated by interaction of a PAI-1 binding protein (PAI
      1 mRNABp) with PAI-1 mRNA. We found that an approximately 60 kD cytoplasmic PAI-1
      mRNABp is detectable in cytoplasmic extracts of MeT5A human pleural mesothelial
      and malignant mesothelioma cells. The PAI-1 mRNABp specifically binds to a 33-nt
      sequence in the 3' untranslated region of PAI-1 mRNA. Insertion of this 33-nt
      sequence destabilizes otherwise stable beta-globin mRNA, indicating that the
      binding sequence accelerates decay of endogenous PAI-1 mRNA. Competitive
      inhibition by overexpression of the 33-nt binding sequence in MeT5A cells reduced
      PAI-1 mRNA decay and increased PAI-1 protein and mRNA expression, indicating that
      the PAI-1 mRNABp destabilizes PAI-1 mRNA by its interaction with the endogenous
      33-nt binding sequence. Incubation of Met5A cells with TGF-beta attenuated the
      interaction of the PAI-1 mRNABp with the 33-nt sequence. By conventional and
      affinity purification, we isolated the PAI-1 mRNABp and confirmed its identity as
      6-phospho-d-gluconate-NADP oxidoreductase, which specifically interacts with the
      full-length and the 33-nt sequence of the PAI-1 mRNA 3' untranslated region. This
      newly recognized pathway could influence expression of PAI-1 by mesothelial or
      mesothelioma cells at the level of mRNA stability in the context of pleural
      inflammation or malignancy.

PMID- 19855087
TI  - Fas ligand expression on T cells is sufficient to prevent prolonged airway
      inflammation in a murine model of asthma.
AB  - Our previous studies revealed that, in a murine model of asthma, mice that
      received Fas-deficient T cells developed a prolonged phase of airway
      inflammation, mucus production, and airway hyperreactivity that failed to resolve
      even 6 weeks after the last challenge. To investigate how Fas-Fas ligand (FasL)
      interaction occurs between T cells and other cells in vivo, Gld mice with
      abnormalities of the FasL signaling pathway were used. The reconstituted mice
      were made by transferring T cells from B6 or Gld mice to Rag(-/-) or FasL
      deficient Rag(-/-) mice. We found that Rag(-/-) mice that received B6 T cells
      resolved the airway inflammation, whereas FasL-deficient Rag(-/-) mice that
      received Gld T cells developed a prolonged airway inflammation at Day 28, with
      decreased IFN-gamma production. Both FasL-deficient Rag(-/-) mice that received
      B6 T cells and Rag(-/-) mice that received Gld T cells also had completely
      resolved their airway inflammation by Day 28 after challenge. Interestingly, FasL
      deficient Rag(-/-) mice that received Gld T cells eventually resolved airway
      inflammation at Day 42, with a similar level of IFN-gamma production to that of
      control group. These results demonstrate that FasL expression on either T cells
      only or non-T cells only was sufficient for the eventual resolution of airway
      inflammation, and the prolonged airway inflammation in FasL-deficient Rag(-/-)
      mice that received Gld T cells was correlated with decreased IFN-gamma production
      by Gld T cells.

PMID- 19855088
TI  - Rapid regulation of K(ATP) channel activity by 17{beta}-estradiol in pancreatic
      {beta}-cells involves the estrogen receptor {beta} and the atrial natriuretic
      peptide receptor.
AB  - The ATP-sensitive potassium (K(ATP)) channel is a key molecule involved in
      glucose-stimulated insulin secretion. The activity of this channel regulates beta
      cell membrane potential, glucose- induced [Ca(2+)](i) signals, and insulin
      release. In this study, the rapid effect of physiological concentrations of
      17beta-estradiol (E2) on K(ATP) channel activity was studied in intact beta-cells
      by use of the patch-clamp technique. When cells from wild-type (WT) mice were
      used, 1 nm E2 rapidly reduced K(ATP) channel activity by 60%. The action of E2 on
      K(ATP) channel was not modified in beta-cells from ERalpha-/- mice, yet it was
      significantly reduced in cells from ERbeta-/- mice. The effect of E2 was mimicked
      by the ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). Activation of
      ERbeta by DPN enhanced glucose-induced Ca(2+) signals and insulin release.
      Previous evidence indicated that the acute inhibitory effects of E2 on K(ATP)
      channel activity involve cyclic GMP and cyclic GMP-dependent protein kinase. In
      this study, we used beta-cells from mice with genetic ablation of the membrane
      guanylate cyclase A receptor for atrial natriuretic peptide (also called the
      atrial natriuretic peptide receptor) (GC-A KO mice) to demonstrate the
      involvement of this membrane receptor in the rapid E2 actions triggered in beta
      cells. E2 rapidly inhibited K(ATP) channel activity and enhanced insulin release
      in islets from WT mice but not in islets from GC-A KO mice. In addition, DPN
      reduced K(ATP) channel activity in beta-cells from WT mice, but not in beta-cells
      from GC-A KO mice. This work unveils a new role for ERbeta as an insulinotropic
      molecule that may have important physiological and pharmacological implications.

PMID- 19855089
TI  - Minireview: the melanocortin 2 receptor accessory proteins.
AB  - The melanocortin 2 receptor (MC2R) accessory protein, MRAP, is one of a growing
      number of G protein-coupled receptor accessory proteins that have been identified
      in recent years that add control and complexity to G protein-coupled receptor
      functional expression and signal transduction. MRAP interacts directly with MC2R
      and is essential for its trafficking from the endoplasmic reticulum to the cell
      surface, where it acts as the receptor for the pituitary hormone ACTH. In
      addition, MRAP2, a newly described homolog of MRAP, is also able to support the
      cell surface expression of MC2R. Although it is clear that MRAP is required for
      MC2R function, the mechanism of MRAP action is only beginning to be understood.
      Recent work has started to reveal some of these mechanisms and the MRAP domains
      involved in MC2R functional expression, and new data have shown a potential role
      for both MRAP and MRAP2 in the regulation of the other melanocortin receptors.

PMID- 19855090
TI  - The IGF-I receptor can alter the matrix metalloproteinase repertoire of tumor
      cells through transcriptional regulation of PKC-{alpha}.
AB  - The IGF-I receptor (IGF-IR) was identified as a tumor progression factor, but its
      role in invasion and metastasis has been the subject of some controversy.
      Previously we reported that in murine lung carcinoma M-27 cells, overexpression
      of IGF-IR increased the synthesis and activation of matrix metalloproteinase
      (MMP)-2 via Akt/phosphatidylinositol 3-kinase signaling. In contrast, we show
      here that in these and other cells, IGF-IR overexpression reduced the
      constitutive and phorbol 12-myristate 13-acetate (PMA)-inducible expression of
      three protein kinase C (PKC)-regulated metalloproteinases, MMP-3, MMP-9, and MMP
      13, in cultured cells as well as in vivo in sc tumors. To elucidate the
      underlying mechanism, we analyzed the effect of IGF-IR on PKC expression and
      activity using wild-type and IGF-IR-overexpressing (M-27(IGFIR)) tumor cells. Our
      results show that overexpression and activation of IGF-IR reduced PKC-alpha
      expression, PKC activity, and downstream ERK1/2 signaling, and these effects were
      reversed in cells expressing kinase (Y(1131,1135,1136)F) or C-terminal
      (Y(1250/51)F) domain mutants of IGF-IR. This reduction was due to transcriptional
      down-regulation of PKC-alpha as evidenced by reduced PKC-alpha mRNA expression in
      a phosphatidylinositol 3-kinase-dependent manner and a blockade of PKC-alpha
      promoter activation as revealed by a reporter gene assay. Finally, reconstitution
      of PKC-alpha levels could restore MMP-9 expression levels in these cells.
      Collectively, these results show that IGF-IR can inhibit PKC-alpha gene
      transcription and thereby block the synthesis of PMA-regulated MMPs, suggesting
      that within the same cells, IGF-IR can act as both a positive and negative
      regulator of MMP expression and function.

PMID- 19855091
TI  - HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via
      modulating Hsp90 acetylation in castration-resistant prostate cancer.
AB  - The development of castration-resistant prostate cancer (PCa) requires that under
      castration conditions, the androgen receptor (AR) remains active and thus
      nuclear. Heat shock protein 90 (Hsp90) plays a key role in androgen-induced and 
      independent nuclear localization and activation of AR. Histone deacetylase 6
      (HDAC6) is implicated, but has not been proven, in regulating AR activity via
      modulating Hsp90 acetylation. Here, we report that knockdown of HDAC6 in C4-2
      cells using short hairpin RNA impaired ligand-independent nuclear localization of
      endogenous AR and inhibited PSA expression and cell growth in the absence or
      presence of dihydrotestosterone (DHT). The dose-response curve of DHT-stimulated
      C4-2 colony formation was shifted by shHDAC6 such that approximately 10-fold
      higher concentration of DHT is required, indicating a requirement for HDAC6 in AR
      hypersensitivity. HDAC6 knockdown also inhibited C4-2 xenograft tumor
      establishment in castrated, but not in testes-intact, nude mice. Studies using
      HDAC6-deficient mouse embryonic fibroblasts cells showed that inhibition of AR
      nuclear localization by HDAC6 knockdown can be largely alleviated by expressing a
      deacetylation mimic Hsp90 mutant. Taken together, our studies suggest that HDAC6
      regulates AR hypersensitivity and nuclear localization, mainly via modulating
      HSP90 acetylation. Targeting HDAC6 alone or in combination with other therapeutic
      approaches is a promising new strategy for prevention and/or treatment of
      castration-resistant PCa.

PMID- 19855093
TI  - Deficiency of ferritin heavy-chain nuclear import in triple a syndrome implies
      nuclear oxidative damage as the primary disease mechanism.
AB  - Triple A syndrome is a rare autosomal recessive disorder characterized by ACTH
      resistant adrenal failure, alacrima, achalasia, and progressive neurological
      manifestations. The majority of cases are associated with mutations in the AAAS
      gene, which encodes a novel, 60-kDa WD-repeat nuclear pore protein, alacrima
      achalasia-adrenal insufficiency neurological disorder (ALADIN) of unknown
      function. Our aim was to elucidate the functional role of ALADIN by determining
      its interacting protein partners using the bacterial two-hybrid (B2-H) technique.
      Nonidentical cDNA fragments were identified from both a HeLa S-3 cell and human
      cerebellar cDNA library that encoded the full-length ferritin heavy chain protein
      (FTH1). This interaction was confirmed by both co-immunoprecipitation and
      fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer
      studies. Immunoblotting showed that fibroblasts from triple A patients (with
      known AAAS mutations) lack nuclear FTH1, suggesting that the nuclear
      translocation of FTH1 is defective. Cells transfected with FTH1 and visualized by
      confocal microscopy had very little nuclear FTH1, but when cotransfected with
      AAAS, FTH1 is readily visible in the nuclei. Therefore, FTH1 nuclear
      translocation is enhanced when ALADIN is coexpressed in these cells. In addition
      to its well known iron storage role, FTH1 has been shown to protect the nucleus
      from oxidative damage. Apoptosis of neuronal cells induced by hydrogen peroxide
      was significantly reduced by transfection of AAAS or by FTH1 or maximally by both
      genes together. Taken together, this work offers a plausible mechanism for the
      progressive clinical features of triple A syndrome.

PMID- 19855092
TI  - Sialic acid modification of adiponectin is not required for multimerization or
      secretion but determines half-life in circulation.
AB  - Adiponectin is an adipocyte-secreted, insulin-sensitizing hormone the circulating
      levels of which are reduced in conditions of insulin resistance and diabetes.
      Previous work has demonstrated the importance of posttranslational modifications,
      such as proline hydroxylation and lysine hydroxylation/glycosylation, in
      adiponectin oligomerization, secretion, and function. Here we describe the first
      functional characterization of adiponectin sialylation. Using a variety of
      biochemical approaches we demonstrated that sialylation occurs on previously
      unidentified O-linked glycans on Thr residues of the variable domain in human
      adiponectin. Enzymatic removal of sialic acid or its underlying O-linked sugars
      did not affect adiponectin multimer composition. Expression of mutant forms of
      adiponectin (lacking the modified Thr residues) or of wild-type adiponectin in
      cells defective in sialylation did not compromise multimer formation or
      secretion, arguing against a structural role for this modification. Activity of
      desialylated adiponectin was comparable to control adiponectin in L6 myotubes and
      acute assays in adiponectin(-/-) mice. In contrast, plasma clearance of
      desialylated adiponectin was accelerated compared with that of control
      adiponectin, implicating a role for this modification in determining the half
      life of circulating adiponectin. Uptake of desialylated adiponectin by isolated
      primary rat hepatocytes was also accelerated, suggesting a role for the hepatic
      asialoglycoprotein receptor. Finally, after chronic administration in
      adiponectin(-/-) mice steady-state levels of desialylated adiponectin were lower
      than control adiponectin and failed to recapitulate the improvements in glucose
      and insulin tolerance tests observed with control adiponectin. These data suggest
      an important role for sialic acid content in the regulation of circulating
      adiponectin levels and highlight the importance of understanding mechanisms
      regulating adiponectin sialylation/desialylation.

PMID- 19855094
TI  - Religion in the face of uncertainty: an uncertainty-identity theory account of
      religiousness.
AB  - The authors characterize religions as social groups and religiosity as the extent
      to which a person identifies with a religion, subscribes to its ideology or
      worldview, and conforms to its normative practices. They argue that religions
      have attributes that make them well suited to reduce feelings of self
      uncertainty. According to uncertainty-identity theory, people are motivated to
      reduce feelings of uncertainty about or reflecting on self; and identification
      with groups, particularly highly entitative groups, is a very effective way to
      reduce uncertainty. All groups provide belief systems and normative prescriptions
      related to everyday life. However, religions also address the nature of
      existence, invoking sacred entities and associated rituals and ceremonies. They
      are entitative groups that provide a moral compass and rules for living that
      pervade a person's life, making them particularly attractive in times of
      uncertainty. The authors document data supporting their analysis and discuss
      conditions that transform religiosity into religious zealotry and extremism.

PMID- 19855095
TI  - Next-generation sequencing: a new revolution in molecular diagnostics?

PMID- 19855096
TI  - Lobelane inhibits methamphetamine-evoked dopamine release via inhibition of the
      vesicular monoamine transporter-2.
AB  - Lobeline is currently being evaluated in clinical trials as a methamphetamine
      abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine
      transporters (DATs), and vesicular monoamine transporters (VMAT2s).
      Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic
      vesicles, resulting ultimately in increased extracellular DA. The present study
      generated structure-activity relationships by defunctionalizing the lobeline
      molecule and determining effects on [(3)H]dihydrotetrabenazine binding,
      inhibition of [(3)H]DA uptake into striatal synaptic vesicles and synaptosomes,
      the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA
      release. Compared with lobeline, the analogs exhibited greater potency inhibiting
      DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane,
      exhibited high potency (K(i) = 45 nM) inhibiting vesicular [(3)H]DA uptake, and
      lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited
      67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function
      compared to DAT function. Lobelane potently decreased (IC(50) = 0.65 microM;
      I(max) = 73%) methamphetamine-evoked DA overflow, and with a greater maximal
      effect compared with lobeline (IC(50) = 0.42 microM, I(max) = 56.1%). These
      results provide support for VMAT2 as a target for inhibition of methamphetamine
      effects. Both trans-isomers and demethylated analogs of lobelane had reduced or
      unaltered potency inhibiting VMAT2 function and lower maximal inhibition of
      methamphetamine-evoked DA release compared with lobelane. Thus,
      defunctionalization, cis-stereochemistry of the side chains, and presence of the
      piperidino N-methyl are structural features that afford greatest inhibition of
      methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The
      current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits
      methamphetamine-evoked DA release and is a promising lead for the development of
      a pharmacotherapeutic for methamphetamine abuse.

PMID- 19855098
TI  - Identification and analysis of two splice variants of human G2A generated by
      alternative splicing.
AB  - G2A is a G protein-coupled receptor that can be induced by various stressors. G2A
      is reported to have proton-sensing activity that mediates intracellular inositol
      phosphate (IP) accumulation with decreasing pH. We previously showed that G2A is
      also activated by some oxidized free fatty acids such as 9-hydroxyoctadecadienoic
      acid (9-HODE). In this study, we identified a novel alternative splice variant of
      G2A (G2A-b) that has a partially different N terminus compared with the G2A
      originally reported (G2A-a). The two splice variants of G2A show similar tissue
      distributions, but G2A-b is expressed more abundantly. There was no difference
      between the two variants in 9-HODE-induced cellular responses, such as
      intracellular calcium mobilization and GDP/GTP exchange of Galpha protein, and in
      proton-sensitive IP accumulation. However, G2A-b showed a higher basal activity
      in terms of IP accumulation. Mutagenesis study revealed that the difference in
      the basal activity is attributable to the K7 residue that exists only in G2A-a.
      We further demonstrated that an R42A mutation largely impaired both the basal and
      proton-sensing activities, but did not affect the 9-HODE-induced intracellular
      calcium increase. Taken together, we found an additional novel G2A variant (G2A
      b) that is the major transcript with functional response to ligand stimulation as
      well as G2A-a, and succeeded in discriminating proton-sensing and oxidized fatty
      acid-sensing activities of G2A.

PMID- 19855097
TI  - CYP2C9*1B promoter polymorphisms, in linkage with CYP2C19*2, affect phenytoin
      autoinduction of clearance and maintenance dose.
AB  - The commonly prescribed antiepileptic drug phenytoin has a narrow therapeutic
      range and wide interindividual variability in clearance explained in part by
      CYP2C9 and CYP2C19 coding variants. After finding a paradoxically low urinary
      phenytoin metabolite (S)/(R) ratio in subjects receiving phenytoin maintenance
      therapy with a CYP2C9*1/*1 and CYP2C19*1/*2 genotype, we hypothesized that CYP2C9
      regulatory polymorphisms (rPMs), G-3089A and -2663delTG, in linkage
      disequilibrium with CYP2C19*2 were responsible. These rPMs explained as much as
      10% of the variation in phenytoin maintenance dose in epileptic patients, but
      were not correlated with other patients' warfarin dose requirements or with
      phenytoin metabolite ratio in human liver microsomes. We hypothesized the rPMs
      affected CYP2C9 induction by phenytoin, a pregnane X receptor (PXR), and
      constitutive androstane receptor (CAR) activator. Transfection studies showed
      that CYP2C9 reporters with wild-type versus variant alleles had similar basal
      activity but significantly greater phenytoin induction by cotransfected PXR, CAR,
      and Nrf2 and less Yin Yang 1 transcription factor repression. Phenytoin induction
      of CYP2C9 was greater in human hepatocytes with the CYP2C9 wild type versus
      variant haplotype. Therefore, CYP2C9 rPMs affect phenytoin-dependent induction of
      CYP2C9 and phenytoin metabolism in humans, with an effect size comparable with
      that for CYP2C9*2 and 2C9*3. These findings may also be relevant to the clinical
      use of other PXR, CAR, and Nrf2 activators.

PMID- 19855099
TI  - Sigma-1 receptors regulate Bcl-2 expression by reactive oxygen species-dependent
      transcriptional regulation of nuclear factor kappaB.
AB  - The expression of Bcl-2, the major antiapoptotic member of the Bcl-2 family, is
      under complex controls of several factors, including reactive oxygen species
      (ROS). The sigma-1 receptor (Sig-1R), which was recently identified as a novel
      molecular chaperone at the mitochondria-associated endoplasmic reticulum membrane
      (MAM), has been shown to exert robust cellular protective actions. However,
      mechanisms underlying the antiapoptotic action of the Sig-1R remain to be
      clarified. Here, we found that the Sig-1R promotes cellular survival by
      regulating the Bcl-2 expression in Chinese hamster ovary cells. Although both Sig
      1Rs and Bcl-2 are highly enriched at the MAM, Sig-1Rs neither associate
      physically with Bcl-2 nor regulate stability of Bcl-2 proteins. However, Sig-1Rs
      tonically regulate the expression of Bcl-2 proteins. Knockdown of Sig-1Rs down
      regulates whereas overexpression of Sig-1Rs up-regulates bcl-2 mRNA, indicating
      that the Sig-1R transcriptionally regulates the expression of Bcl-2. The effect
      of Sig-1R small interfering RNA down-regulating Bcl-2 was blocked by ROS
      scavengers and by the inhibitor of the ROS-inducible transcription factor nuclear
      factor kappaB (NF-kappaB). Knockdown of Sig-1Rs up-regulates p105, the precursor
      of NF-kappaB, while concomitantly decreasing inhibitor of nuclear factor
      kappaBalpha. Sig-1R knockdown also accelerates the conversion of p105 to the
      active form p50. Lastly, we showed that knockdown of Sig-1Rs potentiates H(2)O(2)
      induced apoptosis; the action is blocked by either the NF-kappaB inhibitor
      oridonin or overexpression of Bcl-2. Thus, these findings suggest that Sig-1Rs
      promote cell survival, at least in part, by transcriptionally regulating Bcl-2
      expression via the ROS/NF-kappaB pathway.

PMID- 19855100
TI  - Etravirine for HIV-I: addressing the limitations of the nonnucleoside reverse
      transcriptase inhibitor class.
AB  - Etravirine (ETR) is a second-generation nonnucleoside reverse transcriptase
      inhibitor (NNRTI) specifically designed for treatment-experienced patients
      infected with HIV-1. Its unique strength over other, older agents in the NNRTI
      class is its higher genetic barrier to resistance, allowing it to be used
      effectively in patients with limited treatment options. The arrival of ETR in the
      market has made sequential NNRTI therapy possible for the first time in the
      history of HIV treatment, as it can maintain virologic activity in the presence
      of certain (and sometimes multiple) NNRTI mutations. Although ETR has
      demonstrated efficacy in treatment-experienced and NNRTI-resistant patients in
      large trials, further analyses on its resistance profile are ongoing. As new data
      emerge on the weighting of ETR's resistance-associated mutations (RAMs),
      investigators and clinicians will no doubt be able to further characterize its
      specific place in the HIV treatment armamentarium.

PMID- 19855101
TI  - Coupling tree-ring delta13C and delta15N to test the effect of fertilization on
      mature Douglas-fir (Pseudotsuga menziesii var. glauca) stands across the Interior
      northwest, USA.
AB  - Nitrogen (N) fertilization causes long-term increases in biomass production in
      many N-limited forests around the world, but the mechanistic basis underlying the
      increase is often unclear. One possibility, especially in summer-dry climates, is
      that N fertilization increases the efficiency with which a finite water supply is
      consumed to support photosynthesis. This increase is achieved by a reduction in
      the canopy-integrated concentration of internal CO(2) and thus discrimination
      against (13)C. We used stable isotopes of carbon (delta(13)C) in tree rings to
      experimentally test the physiological impact of N fertilization on mature Douglas
      fir (Pseudotsuga menziesii Franco var. glauca) stands across the geographic
      extent of the Intermountain West, USA. The concentration and the stable isotopes
      of N (delta(15)N) in tree rings were also used to assess the presence and
      activity of fertilizer N. We hypothesized that N fertilization would (i) increase
      delta(15)N and N concentration of stemwood relative to non-fertilized stands and
      (ii) increase stemwood delta(13)C as photosynthetic gas exchange responded to the
      additional N. This experiment included two rates of urea addition, 178 kg ha(-1)
      (low) and 357 kg ha(-1) (high), which were applied twice over a 6-year interval
      bracketed by the 18 years of wood production measured in this study. Foliar N
      concentrations measured the year after each fertilization treatment suggest that
      the fertilizer N had been assimilated by the trees (P < 0.001). The N
      fertilization significantly enriched stemwood delta(15)N by 1.3 per thousand at
      the low fertilization rate and by 2.4 per thousand at the high rate (P < 0.001)
      despite variation in soil N between sites. However, we found no significant
      effect of the N fertilizer on delta(13)C of the annual rings (P = 0.76). These
      data lead us to suggest that alternative mechanisms underlie the growth response
      to fertilizer, i.e., increase in canopy area and shifts in biomass allocation.

PMID- 19855102
TI  - The implications of anti-tumour necrosis factor therapy for viral infection in
      patients with inflammatory bowel disease.
AB  - INTRODUCTION: Anti-tumour necrosis factor (TNF) therapy is increasingly used in
      the management of inflammatory bowel disease; however, concerns have been raised
      regarding risk of infection with such drugs. Little is known about their effect
      upon viral infection. SOURCES OF DATA: A search of PubMed using the terms
      'infliximab', 'etanercept', 'adalimumab' or 'anti-TNF therapy' combined with the
      names of specific viruses was performed. A search of cited papers was used to
      identify further relevant reports. AREAS OF AGREEMENT: Numerous reports of the
      use of anti-TNF in patients with chronic or latent viral infection appear in the
      literature. Specific problems related to hepatitis B virus and varicella zoster
      virus may exist. The safety profile of anti-TNF in chronic viral infection is
      generally reassuring. AREAS OF CONTROVERSY: Numerous consensus statements
      relating to pre-treatment serology or vaccination have recently appeared;
      however, significant variation exists in their recommendations. GROWING POINTS:
      Increasing awareness of the implications of anti-TNF therapy on viral infection
      may allow safer use of such drugs. AREAS TIMELY FOR DEVELOPING RESEARCH: The
      clinical and cost-effectiveness of screening for viral infections prior to anti
      TNF requires further study.

PMID- 19855103
TI  - Mathematical modelling of infectious diseases.
AB  - INTRODUCTION: Mathematical models allow us to extrapolate from current
      information about the state and progress of an outbreak, to predict the future
      and, most importantly, to quantify the uncertainty in these predictions. Here, we
      illustrate these principles in relation to the current H1N1 epidemic. SOURCES OF
      DATA: Many sources of data are used in mathematical modelling, with some forms of
      model requiring vastly more data than others. However, a good estimation of the
      number of cases is vitally important. AREAS OF AGREEMENT: Mathematical models,
      and the statistical tools that underpin them, are now a fundamental element in
      planning control and mitigation measures against any future epidemic of an
      infectious disease. Well-parameterized mathematical models allow us to test a
      variety of possible control strategies in computer simulations before applying
      them in reality. AREAS OF CONTROVERSY: The interaction between modellers and
      public-health practitioners and the level of detail needed for models to be of
      use. GROWING POINTS: The need for stronger statistical links between models and
      data. AREAS TIMELY FOR DEVELOPING RESEARCH: Greater appreciation by the medical
      community of the uses and limitations of models and a greater appreciation by
      modellers of the constraints on public-health resources.

PMID- 19855104
TI  - Annotation confidence score for genome annotation: a genome comparison approach.
AB  - MOTIVATION: The massively parallel sequencing technology can be used by small
      research labs to generate genome sequences of their research interest. However,
      annotation of genomes still relies on the manual process, which becomes a serious
      bottleneck to the high-throughput genome projects. Recently, automatic annotation
      methods are increasingly more accurate, but there are several issues. One
      important challenge in using automatic annotation methods is to distinguish
      annotation quality of ORFs or genes. The availability of such annotation quality
      of genes can reduce the human labor cost dramatically since manual inspection can
      focus only on genes with low-annotation quality scores. RESULTS: In this article,
      we propose a novel annotation quality or confidence scoring scheme, called
      Annotation Confidence Score (ACS), using a genome comparison approach. The
      scoring scheme is computed by combining sequence and textual annotation
      similarity using a modified version of a logistic curve. The most important
      feature of the proposed scoring scheme is to generate a score that reflects the
      excellence in annotation quality of genes by automatically adjusting the number
      of genomes used to compute the score and their phylogenetic distance. Extensive
      experiments with bacterial genomes showed that the proposed scoring scheme
      generated scores for annotation quality according to the quality of annotation
      regardless of the number of reference genomes and their phylogenetic distance.
      AVAILABILITY: http://microbial.informatics.indiana.edu/acs

PMID- 19855105
TI  - DEGseq: an R package for identifying differentially expressed genes from RNA-seq
      data.
AB  - SUMMARY: High-throughput RNA sequencing (RNA-seq) is rapidly emerging as a major
      quantitative transcriptome profiling platform. Here, we present DEGseq, an R
      package to identify differentially expressed genes or isoforms for RNA-seq data
      from different samples. In this package, we integrated three existing methods,
      and introduced two novel methods based on MA-plot to detect and visualize gene
      expression difference. AVAILABILITY: The R package and a quick-start vignette is
      available at http://bioinfo.au.tsinghua.edu.cn/software/degseq

PMID- 19855106
TI  - NGSView: an extensible open source editor for next-generation sequencing data.
AB  - SUMMARY: High-throughput sequencing technologies introduce novel demands on tools
      available for data analysis. We have developed NGSView (Next Generation Sequence
      View), a generally applicable, flexible and extensible next-generation sequence
      alignment editor. The software allows for visualization and manipulation of
      millions of sequences simultaneously on a desktop computer, through a graphical
      interface. NGSView is available under an open source license and can be extended
      through a well documented API. AVAILABILITY: http://ngsview.sourceforge.net

PMID- 19855108
TI  - The relative contribution of IVF to the total ongoing pregnancy rate in a
      subfertile cohort.
AB  - BACKGROUND: Although in vitro fertilization (IVF) was introduced more than 30
      years ago, its exact role in the spectrum of fertility treatments has never been
      studied in an unselected population. The aim of this study was to visualize the
      contribution of IVF to the ongoing pregnancy rates in a cohort of newly referred
      subfertile couples. MATERIALS: All new subfertile couples (n = 1391) that were
      referred to our fertility clinic by their general practitioner between January
      2002 and December 2006 were included. Fertility care was provided according to
      the national Dutch fertility guidelines. Data on diagnosis, treatment, mode of
      conception and pregnancy outcome were documented. If follow-up data were missing,
      couples were contacted. Cumulative pregnancy curves were constructed for the
      whole cohort and per diagnostic group. RESULTS: As per December 2008 the overall
      ongoing pregnancy rate was 72.0% (n = 1001). Almost half of the pregnancies were
      conceived spontaneously (45.6%), 19.2% after ovulation induction (OI), 14.0%
      after intrauterine insemination (IUI) and 21.2% after IVF. A quarter (n = 349) of
      couples received IVF treatment, which was successful in 60% of cases. IVF had the
      largest contribution to ongoing pregnancies in patients with 'tubal factor',
      'endometriosis' and 'male factor' (45, 45 and 37%, respectively) while in couples
      with 'unexplained subfertility' and 'ovulation disorders' the contribution to
      ongoing pregnancies of IVF was limited (13 and 4.5%, respectively). CONCLUSIONS:
      In a cohort of subfertile couples, most pregnancies were conceived spontaneously.
      The contribution of IVF to ongoing pregnancy rates was comparable to those of OI
      and IUI. Compared with the pre-IVF era, couples with 'endometriosis', 'tubal
      factor' and 'male subfertility' have benefited most from its introduction.

PMID- 19855109
TI  - Comparative responses to radio and television anti-smoking advertisements to
      encourage smoking cessation.
AB  - While mass media campaigns have been shown to contribute to reductions in smoking
      prevalence, little research has been undertaken on the effectiveness of radio
      advertising as a communication medium. This is despite radio being less expensive
      and having greater reach than television in some low and middle income countries.
      We aimed to explore the potential of radio as an adjunct or alternative to
      televised campaigns by comparing reactions to a radio anti-smoking ad with three
      televised anti-smoking ads, all of which communicated the serious health
      consequences of smoking in an emotionally evocative way. In pre-exposure
      interviews, 18-59-year-old daily smokers (n = 306) were asked to listen to a
      particular radio time slot/watch a particular television program that they
      usually listened to/watched, in which the ad was broadcast. Post-exposure
      interviews were conducted within 3 days of exposure and measured recall,
      recognition, emotional and cognitive responses, and intentions to quit smoking.
      Findings indicate that the radio ad showed similar or slightly higher levels than
      a concurrently aired television ad on understanding (radio: 96%; television:
      95%), believability (radio: 89%; television: 90%), concern about smoking (both
      77%) and motivation to quit (radio: 51%; television: 45%), and significantly
      higher levels of unprompted recall (radio: 20%; television: 6%). It also compared
      well against two subsequent anti-smoking television ads. Emotionally evocative
      radio advertising may be an effective adjunct or alternative to television
      advertising in jurisdictions where there are substantial limits on funds
      available for airing these campaigns, or where the reach of radio outstrips
      television.

PMID- 19855107
TI  - Digit ratios do not serve as anatomical evidence of prenatal androgen exposure in
      clinical phenotypes of polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is heterogeneous in its clinical
      presentation and four major phenotypes have been identified. The precise etiology
      of PCOS is unknown; however, variable exposure to prenatal androgens may be
      responsible for the spectrum of endocrine and metabolic disturbances
      characteristic of this syndrome. Since prenatal testosterone exposure is known to
      decrease the ratio of the second to fourth finger lengths (2D:4D), we
      characterized the left and right hand 2D:4D in women with clinical variants of
      PCOS. We hypothesized that if prenatal androgens were involved in the development
      of the phenotypic spectrum of PCOS, then lower 2D:4D would be differentially
      expressed among clinical variants of the syndrome. METHODS: Digit ratios were
      determined in 98 women diagnosed with PCOS by the 2003 international consensus
      guidelines and in 51 women with regular menstrual cycles, no clinical or
      biochemical signs of hyperandrogenism and normal ovarian morphology. Women with
      PCOS were categorized into four clinical phenotypes (i.e. Frank, Non-PCO,
      Ovulatory and Mild) and 2D:4D among groups were compared by Tukey-Kramer multiple
      comparisons tests. RESULTS: Left (P = 0.77) and right (P = 0.68) hand 2D:4D were
      similar among the four clinical phenotypes and no phenotype of PCOS demonstrated
      a 2D:4D that differed from controls (Left Hand, P = 0.44 and Right Hand, P =
      0.75). CONCLUSIONS: Women with PCOS do not demonstrate finger length patterns
      that are consistent with increased prenatal androgen exposure. These findings do
      not preclude a role for prenatal androgens in the development of PCOS; however,
      low 2D:4D are not a characteristic of PCOS.

PMID- 19855110
TI  - Equine disease surveillance, April to June 2009.

PMID- 19855111
TI  - Salmonella colonisation of laying hens following vaccination with killed and live
      attenuated commercial Salmonella vaccines.
AB  - The aim of this study was to determine the efficacy of a killed Salmonella
      vaccine and three live vaccines in preventing caecal colonisation of Hy-line
      Brown pullets by Salmonella Enteritidis PT 4. The lowest number of Salmonella
      positive birds following the largest challenge (10(8) cfu) was recorded for live
      vaccine 1. However, birds treated with the killed vaccine had a significantly
      lower number of salmonellae in their caeca compared with both the control group
      and the other vaccine groups (P<0.05).

PMID- 19855112
TI  - Evaluation of indwelling intravenous catheters for the regional perfusion of the
      limbs of horses.
AB  - The feasibility of maintaining indwelling intravenous catheters in the saphenous,
      cephalic or palmar digital vein of horses for seven days to infuse antimicrobial
      drugs was investigated in 18 horses. The horses were randomly assigned to six
      groups according to the vein catheterised and whether they received amikacin or
      erythromycin. None of the catheters was replaced more than once, and 11 of the 18
      catheters remained patent for all seven days. Neither the drug administered nor
      the vein catheterised significantly affected the survival of the catheter. In all
      but three cases, complications, including local inflammation, lameness,
      thrombophlebitis and one severe tissue reaction to erythromycin, resolved during
      the seven days.

PMID- 19855113
TI  - Porcine ulcerative dermatitis syndrome in sows: a form of vesicular cutaneous
      lupus erythematosus?
AB  - Severe ulcerative lesions were observed in the skin of two sows in a herd of 540
      hybrid sows. Annular to polycyclic, severe crusting dermal ulcerations were found
      on the abdomen and flanks; moderate lesions were also found at the base of the
      tail and on the perineum. The lesions were histologically characterised as cell
      poor interface dermatitis and folliculitis, basal cell vacuolisation, vesicle
      formation at the dermal-epidermal junction and serocellular crusts. A
      subepidermal mild to moderate band, characterised as a mixed inflammatory
      infiltrate, was present. A test for antinuclear antibodies was negative; however,
      immunofluorescence testing revealed a linear pattern of IgG precipitation in the
      skin. Staphylococcus hyicus was demonstrated in the serocellular crusts of one
      sow. Treatment with antibiotics, topical antiseptics and corticosteroids did not
      improve the sows' condition. Porcine circovirus and porcine respiratory and
      reproductive syndrome virus were not isolated from samples taken at postmortem
      examination. The observed gross lesions, the absence of response to treatment and
      the exclusion of other skin diseases suggested that the sows were affected with
      porcine ulcerative dermatitis syndrome.

PMID- 19855114
TI  - Campylobacter fetus subspecies venerealis transport medium for enrichment and
      PCR.

PMID- 19855115
TI  - Pemphigus foliaceus in a barbary sheep (Ammotragus lervia).

PMID- 19855116
TI  - Improving communication between vets, SQPs and pharmacists.

PMID- 19855117
TI  - Management of Cushing's syndrome in dogs.

PMID- 19855118
TI  - Suspected hereditary kyphosis and lordosis in Swaledale sheep.

PMID- 19855119
TI  - Circadian clock in Ciona intestinalis revealed by microarray analysis and oxygen
      consumption.
AB  - The molecular mechanisms of the endogenous circadian clocks that allow most
      animals to adapt to environmental cycles have recently been uncovered. The draft
      genome of the ascidian, Ciona intestinalis, a model animal that is close to
      vertebrates, has been described. However, the C. intestinalis genome lacks the
      canonical clock genes such as Per, Bmal and Clock that are shared by vertebrates
      and insects. Here, we found the circadian rhythms at the physiological and
      molecular levels. The oxygen consumption rate was lower during the light phase
      and higher during the dark phase during a day, and the rhythm highly damped and
      continued under constant darkness. From the microarray analysis, the 396 spots
      (1.8% of the total; corresponding to 388 clones) were extracted as candidates for
      circadian expression. We confirmed the circadian expression of several candidate
      genes by northern blotting. Furthermore, three of four rhythmic expressed genes
      showed phase-shifts to prolonged light period. However, most of known clock genes
      did not oscillate. These data suggest that C. intestinalis have a unique
      molecular circadian clock and the daily environmental change is not such a strong
      effect for sea squirt in its evolution when compared to vertebrates and insects.

PMID- 19855120
TI  - Exemplary and surrogate models: two modes of representation in biology.
AB  - Biologists use models in two distinct ways that have not been clearly
      articulated. A model may be used either as an exemplar of a larger group, or as a
      surrogate for a specific target. Zebrafish serve as an exemplary model of
      vertebrates in developmental biology; rodents are both exemplary vertebrates and
      specific surrogates for humans in biomedical research. The distinction between
      exemplary and surrogate models is important, because the criteria for and
      implications of model choice diverge in significant ways, depending on which role
      the model is to serve. So, too, do the kinds of conclusions we can legitimately
      draw from model-based research. The divergence derives in part from the use of
      the two sorts of models to answer different kinds of questions: exemplary models
      most often serve basic research, while surrogate models are used when the target
      species we ultimately want to learn about is inaccessible or difficult to study,
      as in medical research. There are many reasons to consider exemplary and
      surrogate models separately: they are suited to different tasks and contexts,
      rest on different assumptions, and, finally, they have unique limitations.

PMID- 19855121
TI  - Why is modern medicine stuck in a rut?
AB  - There is a growing perception that modern medicine is approaching a state of
      crisis characterized by creative inertia, non-innovation, and non-productivity.
      Compared to the remarkable progress during the first 30 years after World War II,
      the last 30 years have been characterized by a self-congratulatory illusion of
      progress, the fruits of which have failed to reach our patients. The problem may
      lie with the fact that the (often lone) clinical innovator of the past who made
      all the difference to the spectacular progress of medicine during the golden age
      has been marginalized to the extent that he is now an endangered species. The two
      definable forces that have led to his alienation are the hegemony of molecular
      science and the primacy accorded to the randomized clinical trial in biomedical
      research. Both these stifle creative originality-the former by an overdependence
      on complex and technology-driven "big science" and a flawed founding philosophy,
      and the latter by putting limits on our intellectual expectations and a
      bureaucratic approach to scientific research.

PMID- 19855123
TI  - Variational causal claims in epidemiology.
AB  - This article examines definitions of cause in the epidemiological literature.
      Those definitions describe causes as factors that make a difference to the
      distribution of disease or to individual health status. In philosophical terms,
      they are "difference-makers." I argue that those definitions are underpinned by
      an epistemology and a methodology that hinge upon the notion of variation, contra
      the dominant Humean paradigm according to which we infer causality from
      regularity. Furthermore, despite the fact that causes are defined in terms of
      difference-making, this doesn't fix the causal metaphysics but rather reflects
      the "variational" epistemology and methodology of epidemiology. I suggest that
      causality in epidemiology ought to be interpreted according to Williamson's
      epistemic theory. In this approach, causal attribution depends on the available
      evidence and on the methods used. In turn, evidence to establish causal claims
      requires both difference-making and mechanistic considerations.

PMID- 19855122
TI  - The placebo effect: illness and interpersonal healing.
AB  - The placebo effect has been a source of fascination, irritation, and confusion
      within biomedicine over the past 60 years. Although scientific investigation has
      accelerated in the past decade, with particular attention to neurobiological
      mechanisms, there has been a dearth of attention to developing a general theory
      of the placebo effect. In this article, we attempt to address this gap. To set
      the stage, we review evidence relating to the reality and clinical significance
      of the placebo effect. Next we investigate the scope and limits of the placebo
      effect by examining the hypothesis that the placebo effect operates predominantly
      by modifying the experience and perceptions of illness symptoms, such as pain,
      anxiety, and fatigue, rather than by modifying the pathophysiology of disease.
      Based on this background, we characterize the placebo effect as a form of
      interpersonal healing, as distinct from spontaneous natural healing and from
      technological healing dependent on physiologically active pharmaceuticals or
      procedures. Finally, we argue that research on the placebo effect has the
      potential to revitalize the art of medicine.

PMID- 19855124
TI  - The painless brain: lobotomy, psychiatry, and the treatment of chronic pain and
      terminal illness.
AB  - This article examines the use of lobotomy as a treatment for chronic intractable
      pain and reconstructs then-common perceptions of pain and of the patients who
      suffered from it. It delineates the social expectations and judgments implicit in
      physicians' descriptions of the patients, analyzing what was expected from such
      patients and how the medical establishment responded to non-normative expressions
      of suffering. I argue that the medicalized response to an expectation for
      normativity demonstrates the convergence between psychiatric and palliative
      interventions. Based on a historically informed perspective of psychiatric
      interventions in the field of pain medicine, I examine the use of psychiatric
      medications for pain syndromes today and evaluate the interface between
      depression, chronic pain, and terminal illness. While not detracting from the
      medical imperative to alleviate pain, I question the usage of social criteria and
      normative judgments in the clinical decision of how to treat pain. What
      normalizing social function does the use of psychiatric interventions in pain
      treatment fulfill? This approach leads to a reexamination of perceptions of
      dualism in pain medicine.

PMID- 19855125
TI  - Richard Bradley: a unified, living agent theory of the cause of infectious
      diseases of plants, animals, and humans in the first decades of the 18th century.
AB  - During the years 1714 to 1721, Richard Bradley, who was later to become the first
      Professor of Botany at Cambridge University, proposed a unified, unique, living
      agent theory of the cause of infectious diseases of plants and animals and the
      plague of humans. Bradley's agents included microscopic organisms, revealed by
      the studies of Robert Hooke and Antony van Leeuwenhoek. His theory derived from
      his experimental studies of plants and their diseases and from microscopic
      observation of animalcules in different naturally occurring and artificial
      environments. He concluded that there was a microscopic world of "insects" that
      lived and reproduced under the appropriate conditions, and that infectious
      diseases of plants were caused by such "insects." Since there are structural and
      functional similarities between plants and animals, Bradley concluded that
      microscopic organisms caused human and animal infectious diseases as well.
      However, his living agent cause of infectious diseases was not accepted by the
      contemporary scientific society.

PMID- 19855126
TI  - Creativity in biological research.
AB  - During the past century, several biologists have studied the mental processes
      involved in creativity. In recent years psychologists have approached the subject
      experimentally. In one such study (Carson, Peterson, and Higgins 2003),
      creativity has been shown to originate in the subconscious mind and to be
      transmitted to the conscious mind as a result of a decrease in latent inhibition,
      an ordinarily strong cognitive barrier between the conscious mind and the
      subconscious. In my scientific work I have found evidence for creativity in the
      design of experiments, in which the addition of apparently superfluous controls
      has led to important discoveries.

PMID- 19855127
TI  - Compassionate solidarity: suffering, poetry, and medicine.
AB  - Suffering is the experience of distress or disharmony caused by the loss, or
      threatened loss, of what we most cherish. Such losses may strip away the beliefs
      by which we construct a meaningful narrative of human life in general and our own
      in particular. The vocation of physicians and other health professionals is to
      relieve suffering caused by illness, trauma, and bodily degeneration. However,
      since suffering is an existential state that does not necessarily parallel
      physical or emotional states, physicians cannot rely solely on knowledge and
      skills that address physiological dysfunction. Rather, they must learn to engage
      the patient at an existential level. Unfortunately, however, medical pedagogy
      encourages "detached concern," which devalues subjectivity, emotion,
      relationship, and solidarity. The term "compassionate solidarity" summarizes an
      alternative model, which begins with empathic listening and responding, requires
      reflectivity and self-understanding, and is in itself a healing act. Poetry,
      along with other imaginative writing, may help physicians and other health
      professionals grow in self-awareness and gain deeper understanding of suffering,
      empathy, compassion, and symbolic healing.

PMID- 19855128
TI  - An old doctor grows older.
AB  - Abstract:An old man, I am convinced that aging is no disease, but a normal part
      of living, just like childhood. Society should provide for our inevitable decline
      rather than support research to postpone our dying. Retirement, now so arbitrary,
      defines when men and women are old, and so discards contributions from the
      elderly who want to work. As a physician, I am sure that many of us over 65 could
      help to assist the caregivers who have so little time. Ageism is part of the
      problem: medical students learn ageism in their early training, and that ageism
      is reinforced by later contact with the frail sick elderly who come to them for
      care. Aging-and death-have grown invisible to the young. But now that we elderly
      are so many and, thanks to good luck or the Creator's grace, so healthy and still
      so active, we need to exercise the power of our numbers. We have obtained many
      rights, like "early-bird suppers" and discounted bus tickets, but we need to talk
      more about our duties and even about our obligations to the young who will
      someday take our place.

PMID- 19855129
TI  - Melanocyte-like cells in the heart and pulmonary veins contribute to atrial
      arrhythmia triggers.
AB  - Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often
      initiated by ectopic beats arising from the pulmonary veins and atrium, but the
      source and mechanism of these beats remains unclear. The melanin synthesis enzyme
      dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive
      species regulation in melanocytes. Given that dysregulation of intracellular
      calcium and reactive species has been described in patients with atrial
      fibrillation, we investigated the role of DCT in this process. Here, we
      characterize a unique DCT-expressing cell population within murine and human
      hearts that populated the pulmonary veins, atria, and atrioventricular canal.
      Expression profiling demonstrated that this population expressed adrenergic and
      muscarinic receptors and displayed transcriptional profiles distinct from dermal
      melanocytes. Adult mice lacking DCT displayed normal cardiac development but an
      increased susceptibility to atrial arrhythmias. Cultured primary cardiac
      melanocyte-like cells were excitable, and those lacking DCT displayed prolonged
      repolarization with early afterdepolarizations. Furthermore, mice with mutations
      in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did
      not develop atrial arrhythmias in the absence of DCT. These data suggest that
      dysfunction of melanocyte-like cells in the atrium and pulmonary veins may
      contribute to atrial arrhythmias.

PMID- 19855130
TI  - In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF
      alpha.
AB  - Hepatic fibrosis occurs during most chronic liver diseases and is driven by
      inflammatory responses to injured tissue. Because DCs are central to modulating
      liver immunity, we postulated that altered DC function contributes to immunologic
      changes in hepatic fibrosis and affects the pathologic inflammatory milieu within
      the fibrotic liver. Using mouse models, we determined the contribution of DCs to
      altered hepatic immunity in fibrosis and investigated the role of DCs in
      modulating the inflammatory environment within the fibrotic liver. We found that
      DC depletion completely abrogated the elevated levels of many inflammatory
      mediators that are produced in the fibrotic liver. DCs represented approximately
      25% of the fibrotic hepatic leukocytes and showed an elevated CD11b+CD8-
      fraction, a lower B220+ plasmacytoid fraction, and increased expression of MHC II
      and CD40. Moreover, after liver injury, DCs gained a marked capacity to induce
      hepatic stellate cells, NK cells, and T cells to mediate inflammation,
      proliferation, and production of potent immune responses. The proinflammatory and
      immunogenic effects of fibrotic DCs were contingent on their production of TNF
      alpha. Therefore, modulating DC function may be an attractive approach to
      experimental therapeutics in fibro-inflammatory liver disease.

PMID- 19855132
TI  - Autophagy regulates adipose mass and differentiation in mice.
AB  - The relative balance between the quantity of white and brown adipose tissue can
      profoundly affect lipid storage and whole-body energy homeostasis. However, the
      mechanisms regulating the formation, expansion, and interconversion of these 2
      distinct types of fat remain unknown. Recently, the lysosomal degradative pathway
      of macroautophagy has been identified as a regulator of cellular differentiation,
      suggesting that autophagy may modulate this process in adipocytes. The function
      of autophagy in adipose differentiation was therefore examined in the current
      study by genetic inhibition of the critical macroautophagy gene autophagy-related
      7 (Atg7). Knockdown of Atg7 in 3T3-L1 preadipocytes inhibited lipid accumulation
      and decreased protein levels of adipocyte differentiation factors. Knockdown of
      Atg5 or pharmacological inhibition of autophagy or lysosome function also had
      similar effects. An adipocyte-specific mouse knockout of Atg7 generated lean mice
      with decreased white adipose mass and enhanced insulin sensitivity. White adipose
      tissue in knockout mice had increased features of brown adipocytes, which, along
      with an increase in normal brown adipose tissue, led to an elevated rate of fatty
      acid, beta-oxidation, and a lean body mass. Autophagy therefore functions to
      regulate body lipid accumulation by controlling adipocyte differentiation and
      determining the balance between white and brown fat.

PMID- 19855131
TI  - Tregs control the development of symptomatic West Nile virus infection in humans
      and mice.
AB  - West Nile virus (WNV) causes asymptomatic infection in most humans, but for
      undefined reasons, approximately 20% of immunocompetent individuals develop West
      Nile fever, a potentially debilitating febrile illness, and approximately 1%
      develop neuroinvasive disease syndromes. Notably, since its emergence in 1999,
      WNV has become the leading cause of epidemic viral encephalitis in North America.
      We hypothesized that CD4+ Tregs might be differentially regulated in subjects
      with symptomatic compared with those with asymptomatic WNV infection. Here, we
      show that in 32 blood donors with acute WNV infection, Tregs expanded
      significantly in the 3 months after index (RNA+) donations in all subjects.
      Symptomatic donors exhibited lower Treg frequencies from 2 weeks through 1 year
      after index donation yet did not show differences in systemic T cell or
      generalized inflammatory responses. In parallel prospective experimental studies,
      symptomatic WNV-infected mice also developed lower Treg frequencies compared with
      asymptomatic mice at 2 weeks after infection. Moreover, Treg-deficient mice
      developed lethal WNV infection at a higher rate than controls. Together, these
      results suggest that higher levels of peripheral Tregs after infection protect
      against severe WNV disease in immunocompetent animals and humans.

PMID- 19855133
TI  - Tyrosine and serine phosphorylation of alpha-synuclein have opposing effects on
      neurotoxicity and soluble oligomer formation.
AB  - Mutations in the neuronal protein alpha-synuclein cause familial Parkinson
      disease. Phosphorylation of alpha-synuclein at serine 129 is prominent in
      Parkinson disease and influences alpha-synuclein neurotoxicity. Here we report
      that alpha-synuclein is also phosphorylated at tyrosine 125 in transgenic
      Drosophila expressing wild-type human alpha-synuclein and that this tyrosine
      phosphorylation protects from alpha-synuclein neurotoxicity in a Drosophila model
      of Parkinson disease. Western blot analysis of fly brain homogenates showed that
      levels of soluble oligomeric species of alpha-synuclein were increased by
      phosphorylation at serine 129 and decreased by tyrosine 125 phosphorylation.
      Tyrosine 125 phosphorylation diminished during the normal aging process in both
      humans and flies. Notably, cortical tissue from patients with the Parkinson
      disease-related synucleinopathy dementia with Lewy bodies showed less
      phosphorylation at tyrosine 125. Our findings suggest that alpha-synuclein
      neurotoxicity in Parkinson disease and related synucleinopathies may result from
      an imbalance between the detrimental, oligomer-promoting effect of serine 129
      phosphorylation and a neuroprotective action of tyrosine 125 phosphorylation that
      inhibits toxic oligomer formation.

PMID- 19855134
TI  - Great vessel development requires biallelic expression of Chd7 and Tbx1 in
      pharyngeal ectoderm in mice.
AB  - Aortic arch artery patterning defects account for approximately 20% of congenital
      cardiovascular malformations and are observed frequently in velocardiofacial
      syndrome (VCFS). In the current study, we screened for chromosome rearrangements
      in patients suspected of VCFS, but who lacked a 22q11 deletion or TBX1 mutation.
      One individual displayed hemizygous CHD7, which encodes a chromodomain protein.
      CHD7 haploinsufficiency is the major cause of coloboma, heart defect, atresia
      choanae, retarded growth and development, genital hypoplasia, and ear
      anomalies/deafness (CHARGE) syndrome, but this patient lacked the major
      diagnostic features of coloboma and choanal atresia. Because a subset of CHARGE
      cases also display 22q11 deletions, we explored the embryological relationship
      between CHARGE and VCSF using mouse models. The hallmark of Tbx1
      haploinsufficiency is hypo/aplasia of the fourth pharyngeal arch artery (PAA) at
      E10.5. Identical malformations were observed in Chd7 heterozygotes, with
      resulting aortic arch interruption at later stages. Other than Tbx1, Chd7 is the
      only gene reported to affect fourth PAA development by haploinsufficiency.
      Moreover, Tbx1+/-;Chd7+/- double heterozygotes demonstrated a synergistic
      interaction during fourth PAA, thymus, and ear morphogenesis. We could not rescue
      PAA morphogenesis by restoring neural crest Chd7 expression. Rather, biallelic
      expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal
      PAA development.

PMID- 19855135
TI  - Inactivation of Notch signaling in the renal collecting duct causes nephrogenic
      diabetes insipidus in mice.
AB  - The heterogeneous cellular composition of the mammalian renal collecting duct
      enables regulation of fluid, electrolytes, and acid-base homeostasis, but the
      molecular mechanism of its development has yet to be elucidated. The Notch
      signaling pathway is involved in cell fate determination and has been implicated
      in proximal-distal patterning in the mammalian kidney. To investigate the role of
      Notch signaling in renal collecting duct development, we generated mice in which
      Mind bomb-1 (Mib1), an E3 ubiquitin ligase required for the initiation of Notch
      signaling, was specifically inactivated in the ureteric bud of the developing
      kidney. Mice lacking Mib1 in the renal collecting duct displayed increased
      urinary production, decreased urinary osmolality, progressive hydronephrosis,
      sodium wasting, and a severe urinary concentrating defect manifested as
      nephrogenic diabetes insipidus. Histological analysis revealed a diminished
      number of principal cells and corresponding increase in the number of
      intercalated cells. Transgenic overexpression of Notch intracellular domain
      reversed the altered cellular composition of mutant renal collecting duct, with
      principal cells occupying the entire region. Our data demonstrate that Notch
      signaling is required for the development of the mammalian renal collecting duct
      and principal cell differentiation and indicate that pathway dysregulation may
      contribute to distal renal tubular disorders.

PMID- 19855137
TI  - Steroid hormones are produced at the sites of action.

PMID- 19855136
TI  - The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP
      independent chondrogenesis and zebrafish embryo ventralization.
AB  - Patients with classic fibrodysplasia ossificans progressiva, a disorder
      characterized by extensive extraskeletal endochondral bone formation, share a
      recurrent mutation (R206H) within the glycine/serine-rich domain of ACVR1/ALK2, a
      bone morphogenetic protein type I receptor. Through a series of in vitro assays
      using several mammalian cell lines and chick limb bud micromass cultures, we
      determined that mutant R206H ACVR1 activated BMP signaling in the absence of BMP
      ligand and mediated BMP-independent chondrogenesis that was enhanced by BMP. We
      further investigated the interaction of mutant R206H ACVR1 with FKBP1A, a
      glycine/serine domain-binding protein that prevents leaky BMP type I receptor
      activation in the absence of ligand. The mutant protein exhibited reduced binding
      to FKBP1A in COS-7 simian kidney cell line assays, suggesting that increased BMP
      pathway activity in COS-7 cells with R206H ACVR1 is due, at least in part, to
      decreased binding of this inhibitory factor. Consistent with these findings, in
      vivo analyses of zebrafish embryos showed BMP-independent hyperactivation of BMP
      signaling in response to the R206H mutant, resulting in increased embryonic
      ventralization. These data support the conclusion that the mutant R206H ACVR1
      receptor in FOP patients is an activating mutation that induces BMP signaling in
      a BMP-independent and BMP-responsive manner to promote chondrogenesis, consistent
      with the ectopic endochondral bone formation in these patients.

PMID- 19855139
TI  - Aberrant right subclavian artery with left carotid-basilar common trunk.

PMID- 19855138
TI  - Use of body mass index and percentage overweight cutoffs to screen Japanese
      children and adolescents for obesity-related risk factors.
AB  - BACKGROUND: Cutoffs based on percentage overweight (POW) are used for screening
      students in Japan; however, body mass index (BMI) is more common in the rest of
      the world. To screen for risk factors related to obesity among Japanese primary
      and secondary school students, we compared fasting and postprandial values, and
      the receiver operating characteristic (ROC) curves for the POW and BMI criteria.
      METHODS: The subjects were students aged 10 and 13 years living in Shunan City,
      Japan between 2006 and 2008 (n = 6566). POW and International Obesity Taskforce
      (IOTF) BMI criteria were used to screen for obesity-related risk factors. The
      lower (20%, 18-year-old equivalent: 25 kg/m(2)) and higher (50%, 18-year-old
      equivalent: 30 kg/m(2)) cutoffs were examined, and ROC curves were drawn.
      RESULTS: Fasting cholesterol levels were higher than postprandial levels. The
      prevalences of overweight/obesity were 6.6% to 10.0% using the lower cutoff and
      0.6% to 5.0% using the higher cutoff. Among overweight subjects under fasting
      conditions, dyslipidemia was present in 12% to 52%, hypertriglyceridemia in 29%
      to 54%, hyperglycemia in 11% to 21%, and hypertension in 15% to 40%. Although the
      use of the lower and higher POW cutoffs resulted in lower sensitivity and the
      higher specificity, the POW and BMI ROC curves largely overlapped. However, for
      girls aged 10 years, the POW curve for >or=3 risks factors was lower than that of
      the latter (P = 0.013). CONCLUSIONS: For Japanese aged 10 and 13 years, both BMI
      and POW are useful for risk factor screening. However, subjects may be
      misclassified with dyscholesterolemia if postprandial blood samples are used.

PMID- 19855140
TI  - Limited efficacy of endoscopic third ventriculostomy for hydrocephalus following
      aneurysmal subarachnoid hemorrhage.
AB  - Endoscopic third ventriculostomy (ETV) has not been recognized as a surgical
      option for hydrocephalus following aneurysmal subarachnoid hemorrhage (SAH),
      since hydrocephalus following aneurysmal SAH is considered to result from the
      communicating component. However, obstructions in the ventricular system may
      exist, so ETV could help resolve the condition. The present study evaluated the
      efficacy of ETV for hydrocephalus appearing within one month after aneurysmal
      SAH. This prospective study evaluated a total of 118 patients admitted to our
      hospital with aneurysmal SAH. Nine of 66 surgically treated patients suffered
      hydrocephalus within one month after aneurysmal SAH and 8 underwent ETV. Seven of
      these 8 patients showed no further ventricular enlargement or deterioration in
      consciousness, and required no external cerebrospinal fluid (CSF) drainage at
      least temporarily, and could commence early physical rehabilitation. Four
      patients also experienced cognitive improvements after ETV, but none made a full
      cognitive recovery. Ventriculoperitoneal (VP) shunt was implanted for one patient
      who did not respond to ETV, and the necessity of VP shunt was evaluated including
      the CSF removal test for the other patients, due to residual cognitive impairment
      even after initiating the rehabilitation. Five of the 8 patients eventually had
      VP shunts implanted, and 3 patients, including two patients who improved
      cognitively after ETV, had further cognitive improvements. ETV for hydrocephalus
      following aneurysmal SAH is likely to help manage intracranial pressure. ETV may
      improve cognitive impairment in some patients, but whether the maximum resolution
      is obtained only with ETV remains uncertain. VP shunt implantation should be the
      main treatment for hydrocephalus after aneurysmal SAH, but ETV can be employed as
      a temporary intervention in certain conditions, such as during the waiting period
      for the clearance of aneurysmal SAH.

PMID- 19855142
TI  - Serial angiography of dynamic changes of traumatic middle meningeal arteriovenous
      fistula: case report.
AB  - A 48-year-old woman suffered head trauma and presented with an acute epidural
      hematoma with a linear fracture of the right temporal bone across the middle
      meningeal groove. Initial angiography demonstrated no vascular abnormalities.
      Eight months later, she again suffered head trauma and computed tomography
      demonstrated traumatic subarachnoid hemorrhage. Right external carotid
      angiography revealed a middle meningeal arteriovenous fistula (AVF) which drained
      into the superficial sylvian veins via the sphenoparietal sinus. Serial
      angiography showed progressive dilation of the draining veins, but she refused
      surgical intervention and dropped out of our outpatient clinic. Fifteen years
      after the first head trauma, she presented with subarachnoid hemorrhage.
      Angiography demonstrated formation of venous aneurysms on the drainer of the AVF.
      The dilated superficial sylvian vein was removed together with the ruptured
      venous aneurysm. Histological examination of the drainer revealed an arterialized
      vein. The serial angiographic evaluations revealed dynamic changes of the
      traumatic middle meningeal AVF, including progressive dilation of the drainers,
      simplification of the drainage routes, and the formation of venous aneurysms,
      which presumably represents the entire natural course of traumatic middle
      meningeal AVF manifesting as hemorrhage. The present case of traumatic middle
      meningeal AVF with a deteriorating course suggests that surgical removal or
      embolization of the AVF is strongly indicated if follow-up angiography shows
      dilation of the drainers, which implies increased shunt flow.

PMID- 19855141
TI  - Stereotactic radiosurgery for skull base meningioma.
AB  - Stereotactic radiosurgery is now a treatment option for meningiomas, especially
      for high-risk patients such as those with skull base lesions. The clinical
      outcomes were retrospectively analyzed of stereotactic radiosurgery using the
      Leksell Gamma Knife((R)) performed for 98 patients with 106 skull base
      meningiomas at the University of Tokyo Hospital between June 1990 and April 2006
      and followed up for more than a year. After a median follow-up period of 53.2
      months (range 12.2-204.4 months), local tumor control rates were 86.9% and 78.9%
      at 5 years and 10 years, respectively. Tumors with volume of 4 cm(3) or smaller
      (97.5% vs. 76.1% at 5 years, p = 0.001) and tumors completely included within the
      isodose line of 14 Gy or more (97.5% vs. 67.2% at 5 years, p = 0.0006) had higher
      local control rates. Postoperative residual tumors treated by stereotactic
      radiosurgery were controlled in all 25 cases. Cranial nerve deficits were
      improved, stable, and deteriorated in 12, 64, and 3 patients, respectively, after
      stereotactic radiosurgery. Stereotactic radiosurgery was effective treatment
      method for local control of skull base meningiomas, especially for small or
      postoperative residual tumors. Correct combination of microsurgery and
      radiosurgery leads to excellent local control.

PMID- 19855143
TI  - Surgical treatment of a dural arteriovenous fistula in the superior petrosal
      sinus of an elderly patient with minimal suboccipital craniotomy: case report.
AB  - An 85-year-old woman presented with a dural arteriovenous fistula of the superior
      petrosal sinus manifesting as venous infarction of the cerebellum. Magnetic
      resonance imaging and angiography revealed right cerebellar swelling, venous
      engorgement, and an arteriovenous fistula in the superior petrosal sinus. Our
      initial attempt to obliterate the lesion through a transvenous endovascular
      approach failed, so we successfully treated the fistula via surgical interruption
      of the superior petrosal vein through a small suboccipital craniotomy. Careful
      examination of the pattern of venous drainage is important to determine surgical
      indications. This case indicates that minimally invasive open surgery can be
      effective even in an elderly patient.

PMID- 19855144
TI  - Rupture of a vertebral artery dissecting aneurysm developing immediately after
      trapping of a dissecting aneurysm on the contralateral vertebral artery: case
      report.
AB  - The development of vertebral artery (VA) dissecting aneurysm after trapping of
      the contralateral VA is rare, and rupture of angiographically occult VA
      dissecting aneurysms immediately after trapping is even less common. A 39-year
      old man suffered subarachnoid hemorrhage caused by rupture of a left VA
      dissecting aneurysm. The VA was trapped and the left occipital artery anastomosed
      to the posterior inferior cerebellar artery. Postoperatively, he suddenly
      developed apnea and died of rupture of a right VA dissecting aneurysm.
      Histological examination of the bilateral VAs and the basilar artery disclosed a
      hematoma between the media and the adventitia. This case further confirms the
      need for careful preoperative imaging study of the dissection and all segments of
      the dissected vessel in patients requiring trapping of a VA dissecting aneurysm,
      as well as preservation of VA anterograde flow.

PMID- 19855145
TI  - Coil embolization of an unruptured intracranial aneurysm associated with Behcet's
      disease: case report.
AB  - A 36-year-old male patient with Behcet's disease consulted our hospital for
      treatment of an unruptured intracranial aneurysm. He was neurologically intact.
      He had undergone surgery for an aneurysm of the superior mesenteric artery 2
      years ago and had been followed up because of the aneurysm of the left radial
      artery for 1 year. He had been receiving steroid treatment for 4 years. Three
      dimensional computed tomography angiography identified an aneurysm of the left
      intracranial internal carotid artery. The lesion was treated by coil
      embolization. He was discharged without complications. Intracranial aneurysm
      formation is extremely rare in patients with Behcet's disease. The presence of
      extracranial aneurysms indicates screening for intracranial aneurysms. The
      present case shows that coil embolization can be used to treat unruptured
      intracranial aneurysm in patients with Behcet's disease.

PMID- 19855146
TI  - Ventrally located cervical intramedullary cavernous angioma: selection of
      posterior and anterior approaches: case report.
AB  - A 41-year-old woman presented with a rare cervical intramedullary cavernous
      angioma manifesting as acute paralysis in her left upper extremity. Magnetic
      resonance imaging revealed hematomyelia. Laminectomy (C2-C7) was performed,
      followed by posterior midline myelotomy and removal of the intramedullary
      hematoma and the tumor. She showed marked improvement after the surgery. However,
      3 years and 10 months later the patient showed slight intramedullary bleeding
      located ventrally at the same level. Anterior approach with corpectomy was
      performed. Complete removal of the tumor was attained and salvage surgery was
      performed. Postoperative stabilization was achieved with excellent clinical
      outcome. The anterior approach is useful method as a salvage surgery for
      ventrally located cavernous angioma.

PMID- 19855147
TI  - Delayed enlargement of brain edema after resection of intracranial meningioma:
      two case reports.
AB  - Two patients underwent uneventful total removal of convexity or trigone
      meningioma, but subsequently edema enlarged causing symptoms 3-4 weeks later.
      Gradual improvement was obtained by steroid administration in 1 patient and re
      craniotomy in 1 patient. The histological findings in Case 1 were not confirmed,
      but inflammatory reaction against residual microfibrillar collagen hemostat (MCH)
      may have developed. The specimen from around the cyst in Case 2 showed moderate
      staining for vascular endothelial growth factor (VEGF). VEGF secreted by the
      tumor might have resulted in spread of inflammation due to MCH in the brain
      parenchyma. Furthermore, inflammatory reactions may have obstructed or formed a
      one-way communication in the inferior horn and residual cavity, resulting in
      malabsorption of cerebrospinal fluid. Postoperative edema with the timing in
      these cases is difficult to anticipate. However, the risk of this phenomenon can
      probably be minimized by ensuring that MCH is removed as effectively as possible
      after use, or by refraining from use in the brain parenchyma and by taking care
      to connect the residual cavity to the ventricular system, particularly if the
      tumor contacts a cerebral ventricle.

PMID- 19855148
TI  - Primary squamous cell carcinoma of the frontal sinus treated with en bloc
      resection: case report.
AB  - A 66-year-old man presented with an extremely rare primary frontal sinus squamous
      cell carcinoma who was successfully treated by the extreme radical extended
      frontobasal approach. The tumor was resected en bloc with a clear margin and the
      large defect of the frontal region was reconstructed using a rectus abdominis
      myocutaneous flap. The tumor was well controlled without adjuvant therapy, and no
      recurrence or metastasis had occurred 2 years after the operation. Frontal sinus
      malignancy can be resected by the extreme radical extended frontobasal approach.
      The rectus abdominis myocutaneous flap is useful for the large defect of the skin
      and frontal base.

PMID- 19855149
TI  - Efficacy of multi-staged surgery and adjuvant chemotherapy for successful
      treatment of atypical choroid plexus papilloma in an infant: case report.
AB  - A 12-month-old girl presented with a rare atypical choroid plexus papilloma
      manifesting as conscious disturbance and vomiting. Magnetic resonance (MR)
      imaging revealed a well-delineated 5 x 6-cm lobulate mass in the right lateral
      ventricle. Only partial removal of the tumor was performed because of excessive
      intraoperative hemorrhage at the first surgery. The histological diagnosis was
      atypical choroid plexus papilloma. To control the intraoperative hemorrhage,
      embolization of the feeding artery was performed before the second surgery, and
      the tumor was macroscopically totally removed. MR imaging disclosed a small
      residual tumor which showed relatively rapid growth. The patient underwent the
      third removal 5 months after the second surgery. Two months later, MR imaging
      showed a cystic lesion with a small nodule adjacent to the midbrain, indicating
      dissemination of the tumor. The lesion was successfully treated with
      chemotherapy. Atypical choroid plexus papilloma was recently defined in the
      classification of the World Health Organization, so clinical data based on these
      criteria are lacking to establish the therapeutic strategy. Total resection of
      atypical choroid plexus papilloma is the most reliable treatment at present.
      However, postoperative chemotherapy should be considered for recurrence or
      dissemination.

PMID- 19855150
TI  - Double lumbosacral lipomas of the dorsal and filar types associated with OEIS
      complex: case report.
AB  - A female baby was born at 37 weeks and 6 days gestation by vaginal delivery with
      omphalocele, exstrophy of the cloaca, and imperforate anus, indicating the
      presence of OEIS complex, a rare combination of defects consisting of omphalocele
      (O), exstrophy of the cloaca (E), imperforate anus (I), and spinal deformity (S),
      associated with lumbosacral lipoma. The most common associated spinal deformity
      is terminal myelocystocele, and spinal lipoma is rare. Constructive interference
      in steady-state magnetic resonance imaging clearly revealed double lipomas, a
      dorsal-type lipoma, located dorsal to the low-lying conus medullaris, and a filar
      type lipoma, revealed by a thickened and fatty filum terminale. After recovery
      from abdominogenital repairs, debulking of the dorsal-type lipoma and untethering
      of the spinal cord by sectioning of the filar-type lipoma were performed at the
      age of 14 months. Neurosurgical treatment for occult spinal dysraphism should be
      undertaken after recovery from the initial series of major abdominogenital
      procedures.

PMID- 19855151
TI  - Migration of the distal end of a ventriculoperitoneal shunt into the abdominal
      wall in an obese patient: case report.
AB  - A 64-year-old obese woman underwent ventriculoperitoneal shunting for
      hydrocephalus associated with subarachnoid hemorrhage. On the 10th postoperative
      day, the distal end of the peritoneal catheter migrated into the abdominal wall
      and she developed a cyst filled with cerebrospinal fluid around the migrated
      catheter. The distal end of the catheter was surgically repositioned. We
      attribute the migration to increased intra-abdominal pressure due to obesity, the
      use of a low friction hydrogel-processed peritoneal catheter, and the presence of
      a large dead space around the catheter. The laparotomy must be closed
      meticulously to prevent this type of migration.

PMID- 19855152
TI  - Atypical epidermoid cyst with repetitive hemorrhages in the supracallosal region:
      case report.
AB  - A 63-year-old man presented with an unusual supracallosal epidermoid cyst with
      repetitive hemorrhages that initially manifested as severe headache in 2003.
      Physical examination found no neurological deficit. Computed tomography
      demonstrated a homogeneously high density mass lesion measuring 3 x 3 cm in the
      supracallosal area, and the clinical diagnosis was cavernous malformation. No
      change occurred in neurological findings except for headache, but the lesion
      underwent hemorrhages several times over a 4-year period and increased in size to
      4 x 5 cm. Surgery revealed a pearly cyst filled with old blood and debris.
      Histological examination disclosed keratinizing, stratified squamous epithelium
      without hair follicles or sebaceous glands, consistent with the diagnosis of
      epidermoid cyst. Surgery was successfully performed without complications such as
      akinetic mutism, motor weakness, or chemical meningitis. The present case
      suggests that epidermoid cyst should be considered in the differential diagnosis
      of suspected cavernous malformation in any location.

PMID- 19855154
TI  - Young investigator awards at the European stroke conference 2009.

PMID- 19855153
TI  - Evolution of vestibular schwannoma after removal of epidermoid cyst of the same
      location: case report.
AB  - A 71-year-old man presented with vestibular schwannoma manifesting as hearing
      disturbance and truncal ataxia 16 years after removal of a cerebellopontine angle
      (CPA) epidermoid cyst, and located adjacent to the remnant lesion. The patient
      first presented with a 6-month history of right trigeminal neuralgia.
      Neuroimaging demonstrated a right CPA lesion, suggestive of an epidermoid cyst.
      Right lateral suboccipital craniotomy was performed and the histological
      diagnosis was epidermoid cyst. A small lesion remained, but the symptoms were
      relieved. Sixteen years later, the patient presented with right auditory
      disturbance, vertigo, and truncal ataxia. Magnetic resonance imaging revealed a
      multiple cystic mass adjacent to the remnant epidermoid cyst in the right CPA.
      The lesion was removed and the histological diagnosis was vestibular schwannoma
      associated with the epidermoid cyst. The irritative effect of the remnant
      epidermoid cyst or surgical procedures may have caused the vestibular schwannoma,
      but no evidence of the evolution of the different types of tumors was found.

PMID- 19855155
TI  - Further analysis of the survival benefit of clodronate.
AB  - Bisphosphonates have a firm role in the treatment of metastatic prostate cancer
      as it has been shown to retard skeletal events secondary to prostate cancer.
      Recent studies also show possible anti-tumor and anti-angiogenic effects from the
      use of bisphosphonates, specifically with the aminobisphosphonates. Clodronate is
      an older first-generation bisphosphonate that has recently been shown to improve
      overall survival in metastatic prostate cancer as reported by Dearnaley and
      colleagues in the September issue of The Lancet Oncology. The finding of improved
      overall survival has significant implications since no therapy to date, except
      for docetaxel-based regimens, has been shown to improve overall survival in
      metastatic prostate cancer. However, this trial also merits further analysis
      since it may affect the clinical conduct of contemporary clinical trials for men
      with prostate cancer.

PMID- 19855156
TI  - Taking aim at novel vaccines market.
AB  - The World Vaccine Congress Washington 2009 was held in Chantilly, VA USA April 2O
      -23rd. The Vaccine congress attracted over 400 participants from across the
      world, including leading vaccine manufacturers, biotechs, governmental agencies,
      NGOs, research and academic institutes, venture capital and legal firms, contract
      service and equipment manufacturers. The speakers covered a wide range of topics,
      including the role of government and regulatory agencies, funding availability,
      research and development, manufacturing, packaging and post vaccine evaluations.
      Past vaccine development efforts have historically focused on infectious
      diseases. With advancements in the field of immunology, molecular biology and
      vaccinology, the vaccine field has begun moving in new directions. "Taking aim at
      novel vaccines market" session chaired by Dr. Una Ryan, Chief Executive Officer
      of Waltham Technologies, was focused on traditional approaches to novel targets
      (nosocomial infections), novel approaches to traditional targets (flu and
      rabies), novel approaches to novel targets (Type 1 diabetes, multiple sclerosis
      and smoking) and vaccines for developing markets (TB, malaria, rabies). The
      importance of collaborations among academic institutions, industries, and
      philanthropic foundations for developing markets was also emphasized.

PMID- 19855157
TI  - Hacking RNA: Hakai promotes tumorigenesis by enhancing the RNA-binding function
      of PSF.
AB  - Hakai, an E3 ubiquitin ligase for the E-cadherin complex, plays a crucial role in
      lowering cell-cell contacts in epithelial cells, a hallmark feature of tumor
      progression. Recently, Hakai was also found to interact with PSF (PTB-associated
      splicing factor). While PSF can function as a DNA-binding protein with a tumor
      suppressive function, its association with Hakai promotes PSF's RNA-binding
      ability and post-transcriptional influence on target mRNAs. Hakai overexpression
      enhanced the binding of PSF to mRNAs encoding cancer-related proteins, while
      knockdown of Hakai reduced the RNA-binding ability of PSF. Furthermore, the
      knockdown of PSF suppressed Hakai-induced cell proliferation. Thus, Hakai can
      affect the oncogenic phenotype both by altering E-cadherin-based intercellular
      adhesions and by increasing PSF's ability to bind RNAs that promote cancer
      related gene expression.

PMID- 19855159
TI  - High resolution imaging of changes in the structure and spatial organization of
      chromatin, gamma-H2A.X and the MRN complex within etoposide-induced DNA repair
      foci.
AB  - The focal accumulation of DNA repair factors, including the MRE11/Rad50/NBS1
      (MRN) complex and the phosphohistone variant gamma-H2A.X, is a key cytological
      feature of the DNA damage response (DDR). Although these foci have been
      extensively studied by light microscopy, there is comparatively little known
      regarding their ultrastructure. Using correlative light microscopy and electron
      spectroscopic imaging (LM/ESI) we have characterised the ultrastructure of
      chromatin and DNA repair foci within the nuclei of normal human fibroblasts in
      response to DNA double-strand breaks (DSBs). The induction of DNA DSBs by
      etoposide leads to a global decrease in chromatin density, which is accompanied
      by the formation of invaginations of the nuclear envelope as revealed by live
      cell microscopy. Using LM/ESI and the immunogold localisation of gamma-H2A.X and
      MRE11 within repair foci, we also observed decondensed 10 nm chromatin fibres
      within repair foci and the accumulation of large non-chromosomal protein
      complexes over three hours recovery from etoposide. At 18 h after etoposide
      treatment, we observed a close juxtapositioning of PML nuclear bodies and late
      repair foci of gamma-H2A.X, which exhibited a highly organised chromatin
      arrangement distinct from earlier repair foci. Finally, the dual immunogold
      labelling of MRE11 with either gamma-H2A.X or NBS1 revealed that gamma-H2A.X and
      the MRN complex are sub-compartmentalised within repair foci at the sub-micron
      scale. Together these data provide the first ultrastructural comparison of gamma
      H2A.X and MRN DNA repair foci, which are structurally dynamic over time and
      strikingly similar in organisation.

PMID- 19855158
TI  - Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell
      induced osteoclast formation.
AB  - PURPOSE: Therapies to target prostate cancer bone metastases have only limited
      effects. New treatments are focused on the interaction between cancer cells, bone
      marrow cells and the bone matrix. Osteoclasts play an important role in the
      development of bone tumors caused by prostate cancer. Since Src kinase has been
      shown to be necessary for osteoclast function, we hypothesized that dasatinib, a
      Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer
      (PC-3) cell-induced osteoclast formation. RESULTS: Dasatinib inhibited RANKL
      induced osteoclast differentiation of bone marrow-derived monocytes with an
      EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to
      differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts,
      and dasatinib inhibited this differentiation. In addition, conditioned medium
      from PC-3 cell cultures was able to differentiate RAW 264.7 cells into
      osteoclasts and this too, was inhibited by dasatinib. Even the lowest
      concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by
      29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by
      collagen 1 release. EXPERIMENTAL DESIGN: We performed in vitro experiments
      utilizing the Src family kinase inhibitor dasatinib to target osteoclast
      activation as a means of inhibiting prostate cancer bone metastases. CONCLUSION:
      Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow
      derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib
      also inhibits osteoclast degradation activity. Inhibiting osteoclast
      differentiation and activity may be an effective targeted therapy in patients
      with prostate cancer bone metastases.

PMID- 19855160
TI  - Tuberculin conversion and leukocyte migration inhibition test after BCG
      vaccination in newborn infants.
AB  - BACKGROUND: There are reports that BCG vaccine take-up may be delayed or poor
      among preterm and low birth weight babies OBJECTIVE: The present study was
      conducted with the objective of (a) studying BCG take-up through tuberculin
      conversion by Mantoux test at 12 weeks and 6 months of age in babies vaccinated
      with BCG at birth and (b) evaluating the Leukocyte Migration Inhibition Test
      (LMIT) in BCG vaccinated babies who did not react to Mantoux test. DESIGN:
      Prospective observational study. METHODS: BCG vaccine was administered to 143
      neonates of 31-41 weeks gestation within 7 days of birth. At 12 weeks of age,
      Purified Protein Derivative (1 TU PPD-RT 23 with Tween 80) was injected to all
      the babies and induration was measured at the injection site after 48 hours.
      Mantoux negative babies were subjected to the LMIT. All the Mantoux test and LMIT
      negative babies were followed up and given another Mantoux test at 6 months.
      Those babies who showed a negative Mantoux test at 6 months and negative LMIT at
      12 weeks were subjected to another LMIT at 6 months. RESULTS: Local BCG reaction
      was exhibited by 95.5% babies at 8 weeks and scar formed in 47.2% of them by
      12(+1) weeks. The tuberculin conversion rate after 12 weeks of BCG vaccination
      was 42.7%. The rate of tuberculin conversion was significantly more in babies
      with birth weight>2500 g as compared to low birth weight babies. Also, the rate
      of tuberculin conversion was significantly more in term infants as compared to
      preterm babies. Six months after BCG vaccination, 41.5% of previously Mantoux
      negative babies showed tuberculin conversion. Overall, 66.4% babies reacted to
      PPD after 6 months. LMIT was positive in 84.1% babies who had a negative Mantoux
      test at 12 weeks. Six months after BCG vaccination, 53.8% of babies who had LMIT
      negative at 3 months became LMIT positive. Thus out of 143 babies, 95.8% had
      either a reactive Mantoux test or positive LMIT 6 months after BCG vaccination.
      There were only 6 babies (4.2%) who did not show adequate responses to BCG
      vaccination. CONCLUSION: Preterm babies of 31 to 36 weeks of gestation and low
      birth weight babies weighing <2,500 gram at birth can be effectively vaccinated
      with BCG vaccine in the early neonatal period. However, tuberculin conversion is
      not a reliable indicator to assess responses induced by BCG vaccination either 12
      weeks or 6 months after vaccination because inspite of negative Mantoux test, the
      vaccinated infant may still be having an adequate response to BCG vaccine. The
      local BCG reaction at 8 weeks corresponds to cell mediated immunity conferred by
      BCG vaccination.

PMID- 19855161
TI  - The role of mTORC1 pathway in intestinal tumorigenesis.
AB  - Activation of the mTORC1 pathway has been implicated in many types of cancer, and
      several mTORC1 inhibitors are currently under clinical trials for treating
      various cancer patients. Notably, Temsirolimus has recently been approved for
      treatment of advanced renal cell carcinoma. However, the role of mTORC1 pathway
      in colorectal tumorigenesis remains largely unknown. We have recently found that
      the mTORC1 pathway is activated in intestinal adenomas of Apc mutant mice,
      accompanied by an elevated level of mTOR protein, and that treatment with RAD001,
      an mTORC1 inhibitor, suppresses the growth of these polyps. Our results suggest
      an important role of mTORC1 pathway in colorectal cancer, as well as a
      therapeutic possibility for mTORC1 inhibitors in its treatment.

PMID- 19855163
TI  - Lung cancer profiling: Genetic and molecular predictors of MEK-dependence.

PMID- 19855162
TI  - Self-organizing actin waves as planar phagocytic cup structures.
AB  - Actin waves that travel on the planar membrane of a substrate-attached cell
      underscore the capability of the actin system to assemble into dynamic structures
      by the recruitment of proteins from the cytoplasm. The waves have no fixed shape,
      can reverse their direction of propagation and can fuse or divide. Actin waves
      separate two phases of the plasma membrane that are distinguished by their lipid
      composition. The area circumscribed by a wave resembles in its phosphoinositide
      content the interior of a phagocytic cup, leading us to explore the possibility
      that actin waves are in-plane phagocytic structures generated without the
      localized stimulus of an attached particle. Consistent with this view, wave
      forming cells were found to exhibit a high propensity for taking up particles.
      Cells fed rod-shaped particles produced elongated phagocytic cups that displayed
      a zonal pattern that reflected in detail the actin and lipid pattern of free
      running actin waves. Neutrophils and macrophages are known to spread on surfaces
      decorated with immune complexes, a process that has been interpreted as
      "frustrated" phagocytosis. We suggest that actin waves enable a phagocyte to scan
      a surface for particles that might be engulfed.

PMID- 19855164
TI  - Interactions between DBC1 and SIRT 1 are deregulated in breast cancer cells.

PMID- 19855165
TI  - Cellular quiescence caused by the Mdm2 inhibitor nutlin-3A.
AB  - Cellular senescence is characterized by irreversible loss of proliferative
      potential and a large, flat cell morphology. Ectopic p21 and doxorubicin induced
      cellular senescence in HT1080 and WI-38-tert cell lines. In the same cell lines,
      the Mdm2 inhibitor nutlin-3a induced p53 but, unexpectedly, caused quiescence
      (reversible arrest) with a small cell morphology. We discuss that Mdm antagonists
      could be used in combination with chemotherapy to reversibly arrest normal cells,
      thus protecting them during chemotherapy of cancer (cyclotherapy).

PMID- 19855167
TI  - Chemotherapy induces ATP release from tumor cells.
AB  - Chemotherapy can induce anticancer immune responses. In contrast to a widely
      extended prejudice, apoptotic cell death is often more efficient in eliciting a
      protective anticancer immune response than necrotic cell death. Recently, we have
      found that purinergic receptors of the P2X7 type are required for the anticancer
      immune response induced by chemotherapy. ATP is the endogenous ligand that has
      the highest affinity for P2X7. Therefore, we investigated the capacity of a panel
      of chemotherapeutic agents to induce ATP release from cancer cells. Here, we
      describe that multiple distinct anticancer drugs reduce the intracellular
      concentration of ATP before and during the manifestation of apoptotic
      characteristics such as the dissipation of the mitochondrial transmembrane
      potential and the exposure of phosphatidylserine residues on the plasma membrane.
      Indeed, as apoptosis progresses, intracellular ATP concentrations decrease,
      although even advanced-stage apoptotic cells still contain sizeable ATP levels.
      Only when cells enter secondary necrosis, the ATP concentration falls to
      undetectable levels. Concomitantly, a wide range of chemotherapeutic agents
      causes the release of ATP into the extracellular space as they induce tumor cell
      death. Hence, ATP release is a general correlate of apoptotic cell death induced
      by conventional anticancer therapies.

PMID- 19855166
TI  - ATX-LPA receptor axis in inflammation and cancer.
AB  - Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) mediates a
      plethora of physiological and pathological activities via interactions with a
      series of high affinity G protein-coupled receptors (GPCR). Both LPA receptor
      family members and autotaxin (ATX/LysoPLD), the primary LPA-producing enzyme, are
      aberrantly expressed in many human breast cancers and several other cancer
      lineages. Using transgenic mice expressing either an LPA receptor or ATX, we
      recently demonstrated that the ATX-LPA receptor axis plays a causal role in
      breast tumorigenesis and cancer-related inflammation, further validating the ATX
      LPA receptor axis as a rich therapeutic target in cancer.

PMID- 19855169
TI  - Targeting biodefense markets.
AB  - The "World Vaccine Congress 2009" held in Washington D.C. (April 20-23, 2009)
      sponsored several sessions focused on the vaccine market targeting biodefense. On
      day one of the congress, a panel discussion outlined the federal progress in
      medical countermeasure preparedness that included emerging infections, influenza,
      and biodefense focuses. The second day, a session focused on the biodefense
      vaccine market with both government and industry members discussing the
      opportunities and challenges associated with the budding market.

PMID- 19855168
TI  - Neuropilin-2 acts as a modulator of Sema3A-dependent glioma cell migration.
AB  - Semaphorin 3A (Sema3A) is a secreted guidance molecule initially described in the
      nervous system. This protein is able to control axon growth but also effects on
      endothelial cells migration. Here, we report that Sema3A acts as a chemorepellent
      factor for the rat C6 glioma cells and three different human glioma cell lines.
      Interestingly, Sema3A triggered a chemoattractive response in a fourth human
      glioma cell line. The nature of the receptor complex ensuring the appropriate
      signaling was dissected in C6 cells by using function blocking antibodies and
      gain- or loss-of function experiments using recombinant receptors. Our results
      demonstrate that neuropilin-1, neuropilin-2 and PlexinA1 are necessary to trigger
      cell repulsion. The selective blockade of neuropilin-1 or Plexin-A1 switched the
      chemorepulsive effect of Sema3A into a chemoattractive one. Strikingly, blocking
      Neuropilin-2 suppressed Sema3A-induced cell migration while overexpression of
      neuropilin-2 was able to convert the chemorepulsive effect of Sema3A into a
      chemoattractive one. Our results not only provide additional evidence for a
      biological function of Sema3A in glioma migration but also reveal part of the
      receptor complex involved. Hence, our study describes a receptor-based plasticity
      in cancer cells leading to opposite migration behavior in response to the same
      extracellular signal.

PMID- 19855170
TI  - Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and
      anogenital disease in subjects with serological evidence of prior vaccine type
      HPV infection.
AB  - OBJECTIVE: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL/SILGARD)
      clinical program, 73% of women aged 16-26 were naive to all vaccine HPV types. In
      these women, prophylactic administration of the vaccine was highly effective in
      preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15%
      of had evidence of past infection with one or more vaccine HPV types
      (seropositive and DNA negative) at the time of enrollment. Here we present an
      analysis in this group of women to determine the efficacy of the HPV 6/11/16/18
      vaccine against new cervical and external anogenital disease related to the same
      vaccine HPV type which had previously been cleared. Vaccine tolerability in this
      previously infected population was also assessed. METHODS: 18,174 women were
      enrolled into 3 clinical studies. The data presented comprise a subset of these
      subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment
      (for >or=1 vaccine type). In each study, subjects were randomized in a 1:1 ratio
      to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6
      (without knowledge of baseline HPV status). Procedures performed for efficacy
      data evaluation included detailed genital examination, Pap testing, and
      collection of cervicovaginal and external genital specimens. Analyses of efficacy
      were carried out in a population stratified by HPV serology and HPV DNA status at
      enrollment. RESULTS: Subjects were followed for an average of 40 months. Seven
      subjects in the placebo group developed cervical disease, and eight subjects
      developed external genital disease related to a vaccine HPV type they had
      previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed
      disease to a vaccine HPV type to which they were seropositive and DNA negative at
      enrolment. CONCLUSIONS: These results suggest that natural HPV infection-elicited
      antibodies may not provide complete protection over time, however the immune
      response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or
      reactivation of disease with vaccine HPV types. Vaccine-related adverse
      experiences were higher among subjects receiving vaccine, mostly due to increased
      injection site adverse experiences.

PMID- 19855172
TI  - Evaluation of p63 and p73 antibodies for cross-reactivity.
AB  - The tumor suppressor p53 is commonly mutated in human cancers. However, two
      homologs of p53, p63 and p73, are frequently overexpressed in tumors and are
      associated with tumor subtypes, clinical outcomes, and responses to therapy.
      There are many isoforms of p53, p63 and p73 (the p53 family). Proper detection of
      and discrimination between the members of this tumor suppressor family in human
      tissues is of critical importance to cancer research and clinical care. In this
      study, we assessed the specificity of several commercially available and newly
      generated p73 antibodies, focusing on antibodies that distinguish between the TA
      p73 and DeltaNp73 isoforms by western analysis, immunohistochemistry, and
      immunofluorescence. In addition, we found that the pan-p63 and pan-p73 antibodies
      tested cross-react with p73 and p63 respectively. The results of this study have
      important implications for analysis of p63 and p73 expression and co-expression
      in human tumors, and for potential use of these reagents in molecular diagnostics
      and therapeutic decision-making.

PMID- 19855174
TI  - Cancer vaccines and immunotherapy.

PMID- 19855173
TI  - CDK5: the "pathfinder" for new born neurons in adult hippocampus?
AB  - Neurogenesis takes place in the mammalian hippocampus throughout the whole life
      and deficient adult hippocampal neurogenesis has been related to neurological
      conditions like Alzheimer disease (AD), Parkinson disease (PD) and epilepsy. The
      molecular mechanisms by which immature neurons and their extending neurites find
      their appropriate position and target area remain largely unknown. Recent work by
      Jessberger et al. examines the role of Cdk5 in normal adult neurogenesis by a
      retroviral knock-down approach. Cdk5 is shown to be implicated in the migration
      of newborn neurons into the granule cell layer (GCL), as well as, in correct
      targeting of dendrites from newborn granule cells (GC) into the molecular layer
      (ML) of the dentate gyrus (DG). The study also shows that aberrant dendrites
      still seem to become synaptically integrated into the existing circuitry thereby
      suggesting a mechanistic dissociation between accurate dendritic targeting and
      subsequent synapse formation. The finding of Cdk5 guiding this integration of new
      born neurons at the physiologically appropriate place is an important step
      towards understanding adult neurogenesis that may help to overcome problems with
      the restorative use of neural stem cells in present grafting approaches in
      neurological diseases.

PMID- 19855175
TI  - Portrait of a leading vaccinologist: dedicated to meningitis and respiratory
      tract infections.
AB  - Since the early days of Jenner, vaccination against infectious agents appeared a
      very efficacious way for preventing millions of deaths and patients with serious
      sequelae. However, only limited success has been obtained in eradicating
      infectious diseases. Smallpox is the only human infectious disease that has been
      eradicated so far by vaccination, and eradication of polio is in its endgame.
      Data from the WHO in 2003 show that 2.5 million children under five still die
      from vaccine preventable diseases, but many more die from the major microbial
      killers in the world, i.e. HIV/AIDS, malaria and tuberculosis for which there are
      no effective vaccines. Very serious morbidity is the consequence of many
      infectious diseases often leading to disablement for a lifetime. As a junior post
      doc with a position in the department of Medical Microbiology at the University
      of Amsterdam, I was touched by the seriousness of bacterial meningitis. This
      laboratory is the National Reference Center for Bacterial Meningitis in the
      Netherlands. It receives more than 80% of all isolates from meningitis patients
      in the country and has access to patient information for epidemiological
      research. This environment triggered me to use my experience as a biochemist with
      a PhD on composition, structure and functioning of the outer membrane of
      Escherichia coli to move from basic microbiology research to research on
      pathogenic bacteria, and ultimately prevention of serious bacterial infections.

PMID- 19855176
TI  - Cep55 stabilization is required for normal execution of cytokinesis.
AB  - Cep55 is a mitotic phosphoprotein that plays an important role in cytokinesis,
      the final stage of cell division during which physical separation of the two
      daughter cells is accomplished. We recently demonstrated that the peptidyl-prolyl
      isomerase Pin1 regulates this cell cycle event by enhancing the Plk1-dependent
      phosphorylation of Cep55. We show here that Cep55 is stabilized post
      translationally during mitosis and that siRNA-mediated knockdown of Pin1 prevents
      this stabilization. Consistent with this, Cep55 is unstable in Pin1 knockout
      mouse embryonic fibroblasts. Moreover, mutation of the Pin1 binding sites in
      Cep55 reduces its stability during mitosis. Mutation of the Plk1 phosphorylation
      site also lowers Cep55 stability, whereas overexpression of Plk1 increases Cep55
      levels, in keeping with Pin1 regulating Plk1-mediated phosphorylation of Cep55.
      Importantly, expression of wild-type Cep55 at levels similar to that of the
      phosphorylation mutants only partially reverts the cytokinesis defect induced by
      depletion of Cep55, indicating that inadequate levels of Cep55 prevent proper
      execution of cytokinesis. Taken together, these data provide more insight into
      the regulation of the final stages of cell division. As cytokinesis defects can
      cause chromosomal instability, knowledge about the processes that regulate normal
      cytokinesis adds to our understanding of events that lead to tumorigenesis.

PMID- 19855177
TI  - Covalent modifications of histones during mitosis and meiosis.
AB  - Higher order chromosome structures are the hallmark of mitotic and meiotic cells.
      Chromatin condensation and compaction are essential for rapid chromosome
      congression and accurate chromosome segregation during cell division. The core
      histones possess tails at their amino-termini. These tails, which extend from the
      surface of the nucleosomes, are highly dynamic and subject to an extensive array
      of covalent modifications. Modified histone tails play an important role, not
      only in the folding of nucleosomal arrays into higher order chromatin structures
      but also in gene regulation. The combination of these distinct covalent
      modifications of histones constitutes "the histone code" that regulates various
      cellular processes, including mitotic and meiotic progression.

PMID- 19855178
TI  - Listeria monocytogenes ActA is a key player in evading autophagic recognition.
AB  - Autophagy is a pivotal bulk degradation system that eliminates undesirable
      molecules, damaged organelles, and misfolded protein aggregates in response to
      diverse stimuli, including infection. Autophagy acts to limit intracellular
      microbial growth but intracellular pathogens have evolved strategies to subvert
      host autophagic responses for their survival. We found that Listeria
      monocytogenes ActA, a surface protein required for actin polymerization and actin
      based bacterial motility, plays a pivotal role in evading autophagy, but in a
      manner independent of bacterial motility. We show that L. monocytogenes exploits
      the biomimetic property of ActA to camouflage itself with host proteins comprised
      of Ena/VASP and the Arp2/3 complex, thereby escaping recognition by autophagy
      (Fig. 1).

PMID- 19855179
TI  - 3D tomography reveals connections between the phagophore and endoplasmic
      reticulum.
AB  - Autophagosomes have been reported to form in the vicinity of the endoplasmic
      reticulum (ER). In many cases, the phagophore membrane is observed between two
      cisternae of rough ER, but it is not known whether these two membranes are
      directly connected. To investigate the relationship of the phagophore membrane
      and the ER, we used electron microscopic tomography of serum and amino acid
      starved normal rat kidney cells. The cells were fixed in glutaraldehyde and
      reduced osmium tetroxide and embedded in Epon. Dual axis tilt image series were
      acquired from two successive 250-nm sections. To analyze the three-dimensional
      (3D) morphology of phagophores and the associated rough ER, 3D tomograms were
      used to model the ER and phagophore membranes. The tomographic reconstructions
      revealed connections between the phagophore/autophagosome membrane and the
      closely located ER cisternae, especially with the ER located inside the
      autophagosome. The connections were typically formed by narrow extensions from
      the phagophore/autophagosome to the ER. This finding has potential implications
      on the origin of autophagosome membranes, and on the mechanism of phagophore
      membrane extension. In addition, we observed lipid droplets in very close contact
      with the phagophores/autophagosomes.

PMID- 19855180
TI  - Circulation status of subintestinal vessels is a sensitive parameter for
      monitoring suboptimal systemic circulation in experimental zebrafish embryos.

PMID- 19855181
TI  - Yin and yang: cancer-implicated miRNAs that have it both ways.

PMID- 19855182
TI  - An unusual case of self-defense.

PMID- 19855183
TI  - Induction of apoptosis by viruses: what role does the nucleolus play?

PMID- 19855184
TI  - Spindle function in yeast: a human motor to the rescue.

PMID- 19855186
TI  - Autophagy as the main means of cytotoxicity by glucocorticoids in hematological
      malignancies.
AB  - Glucocorticoids are fundamental drugs used in the treatment of lymphoid
      malignancies with apoptotic cell death as the hitherto proposed mechanism of
      action. We have recently shown that dexamethasone induces autophagy in lymphoid
      leukemia cells and in this particular setting this cell death modality is a
      prerequisite for the efficient killing of the leukemic cells by dexamethasone.
      Hence, inhibition of autophagy by siRNA-mediated silencing of Beclin 1, as well
      as chemical inhibition of type III PtdIns3K, inhibits apoptosis, demonstrating an
      important role of autophagy in dexamethasone-induced cell death. In this brief
      report, we review these findings and introduce the multiple myeloma cells as a
      novel system to study autophagy in response to dexamethasone.

PMID- 19855187
TI  - Nicotinamide phosphoribosyltransferase regulates cell survival through autophagy
      in cardiomyocytes.
AB  - Nicotinamide adenine dinucleotide (NAD(+)) acts as a transfer molecule for
      electrons, thereby acting as a key cofactor for energy production. NAD(+) also
      serves as a substrate for cellular enzymes, including poly (ADPribose) polymerase
      (PARP)-1 and Sirt1. Activation of PARP-1 by DNA damage depletes the cellular pool
      of NAD(+), leading to necrotic cell death. NAD(+) in the nucleus enhances the
      activity of Sirt1, thereby modulating transcription. NAD(+) is either synthesized
      de novo from amino acids, namely tryptophan and aspartic acid, or resynthesized
      from NAD(+) metabolites, such as nicotinamide (NAM), through the salvage pathway.
      NAM phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the NAD(+)
      salvage pathway. We have recently demonstrated that Nampt is an important
      regulator of NAD(+) and autophagy in cardiomyocytes. Here we discuss the role of
      Nampt in regulating autophagy and potential mechanisms by which NAD(+) regulates
      autophagy in the heart.

PMID- 19855189
TI  - XBP-1 deficiency in the nervous system reveals a homeostatic switch to activate
      autophagy.
AB  - Endoplasmic reticulum (ER) stress has been extensively described in many protein
      misfolding disorders including amyotrophic lateral sclerosis (ALS). Adaptation to
      ER stress is mediated by the activation of an integrated signal transduction
      pathway known as the unfolded protein response (UPR). We have recently defined
      the contribution of X Box binding protein-1 (XBP-1) to ALS, a key UPR
      transcription factor that regulates genes involved in protein folding and quality
      control. Despite expectations that XBP-1 deficiency would enhance the severity of
      experimental ALS, these mice were instead markedly more resistant to developing
      the disease. This phenotype was associated with enhanced clearance of abnormal
      protein aggregates by macroautophagy, a cellular pathway involved in lysosome
      mediated protein degradation. Our results reveal a critical crosstalk between
      these two stress pathways that can provide protection against neurodegeneration.
      Here, we discuss possible signaling pathways that may connect an impaired UPR
      with the induction of autophagy.

PMID- 19855190
TI  - Assessing autophagy in the context of photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a procedure that has applications in the selective
      eradication of neoplasia where sites of malignant lesions are clearly delineated.
      It is a two-step process whereby cells are first sensitized to light and then
      photoirradiated. This results in the formation of singlet molecular oxygen and
      other reactive oxygen species that can cause photodamage at sites where the
      photosensitizing agent has localized. Photosensitizers found to be clinically
      useful show affinity for the endoplasmic reticulum (ER), mitochondria, lysosomes,
      or combinations of these sites. The induction of apoptosis and/or autophagy in
      photosensitized cells is a common outcome of PDT. This report explores the
      following issues: (1) Does the induction of autophagy in PDT protocols occur
      independent of, or in association with, apoptosis? (2) Does the resulting
      autophagy play a prosurvival or prodeath role? (3) Do photosensitizers
      damage/inactivate specific proteins that are components of, or that modulate the
      autophagic process? (4) Can an autophagic response be mounted in cells in which
      lysosomes are specifically photodamaged? In brief, autophagy can occur
      independently of apoptosis in PDT protocols, and appears to play a prosurvival
      role in apoptosis competent cells, and a prodeath role in apoptosis incompetent
      cells. Mitochondrial and ER-localized sensitizers cause selective photodamage to
      some (i.e., Bcl-2, Bcl-x(L), mTOR) proteins involved in the apoptotic/autophagic
      process. Finally, an aborted autophagic response occurs in cells with
      photodamaged lysosomes. Whereas autophagosomes form, digestion of their cargo is
      compromised because of the absence of functional lysosomes.

PMID- 19855191
TI  - RACK1 downregulates levels of the pro-apoptotic protein Fem1b in apoptosis
      resistant colon cancer cells.
AB  - Evasion of apoptosis plays an important role in colon cancer progression.
      Following loss of the Apc tumor suppressor gene in mice, the gene encoding Fem1b
      is upregulated early in neoplastic intestinal epithelium. Fem1b is a pro
      apoptotic protein that interacts with Fas, TNFR1 and Apaf-1, and increased
      expression of Fem1b induces apoptosis of cancer cells. Fem1b is a homolog of FEM
      1, a protein in Caenorhabditis elegans that is negatively regulated by
      ubiquitination and proteasomal degradation. To study Fem1b regulation in colon
      cancer progression, we used apoptotis-sensitive SW480 cells, derived from a
      primary colon cancer, and their isogenic, apoptosis-resistant counterparts SW620
      cells, derived from a subsequent metastatic lesion in the same patient. Treatment
      with proteasome inhibitor increased Fem1b protein levels in SW620 cells, but not
      in SW480 cells. In SW620 cells we found that endogenous Fem1b co
      immunoprecipitates in complexes with RACK1, a protein known to mediate
      ubiquitination and proteasomal degradation of other pro-apoptotic proteins and to
      be upregulated in colon cancer. Full-length Fem1b, or the N-terminal region of
      Fem1b, associated with RACK1 when co-expressed in HEK293T cells, and RACK1
      stimulated ubiquitination of Fem1b. RACK1 overexpression in SW620 cells led to
      downregulation of Fem1b protein levels. Conversely, downregulation of RACK1 led
      to upregulation of Fem1b protein levels, associated with induction of apoptosis,
      and this apoptosis was inhibited by blocking Fem1b protein upregulation. In
      conclusion, RACK1 downregulates levels of the pro-apoptotic protein Fem1b in
      metastatic, apoptosis-resistant colon cancer cells, which may promote apoptosis
      resistance during progression of colon cancer.

PMID- 19855192
TI  - A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP)
      inhibitor reduces cancer cell motility and tumor growth.
AB  - Matrix metalloproteinases (MMPs), and especially membrane type-1 matrix
      metalloproteinase (MT1-MMP, MMP-14), play a role in cancer progression and can
      have a prognostic value. Various synthetic broad-spectrum MMP inhibitors have
      been developed but have had little success in cancer patient treatment owing to
      side effects. Until recently, selective targeting of specific MMPs has not been
      possible due to lack of specific inhibitors. Here we have developed a selective
      MT1-MMP peptide-inhibitor GACFSIAHECGA, which did not affect the activities of
      many other MMPs including MMP-1, -2, -3, -7, -8, -9, -10, -11, -12, -13, -15, -17
      or -20. In a fluorescent peptide cleavage assay it displayed an IC(50) value of
      150 microM. The peptide effectively inhibited the migration and invasion of
      cancer cell lines in vitro. Furthermore, in vivo the peptide reduced the growth
      of tongue carcinoma xenografts and prolonged the survival of mice. Overall these
      results suggest that selective MT1-MMP inhibitors may have utility as anticancer
      agents.

PMID- 19855193
TI  - Two-photon imaging of multicellular tumor spheroids: a novel method for
      evaluating the efficacy of CDC25 phosphatase inhibitors.

PMID- 19855194
TI  - DH166, a beta-carboline derivative, inhibits the kinase activity of PLK1.
AB  - A better way to treat complex diseases such as cancer is to aim for several
      targets at once. Beta-carboline derivatives have been shown to have anticancer
      activity, but these compounds may target several enzymes required for cell
      division. Polo-like kinases (PLKs) are well conserved serine/threonine kinases
      and PLK1 plays multiple roles in cell proliferation. Thus, PLK1 is one of the
      attractive mitotic targets for anticancer drugs. We found that DH166, a beta
      carboline derivative, inhibits the growth of cdc5-2 temperature-sensitive mutant
      more profoundly than wild-type yeast cells. Because Cdc5 is the human PLK1
      homologue in budding yeast, this observation indicates that DH166 might be a PLK1
      inhibitor. Indeed, DH166 inhibits the kinase activity of purified PLK1 at low
      micromolar concentration in an ATP-competitive manner, which is consistent with
      the docking result based on the crystal structure of PLK1. In addition, DH166
      blocks cancer cell proliferation, causes a mitotic arrest, increases cyclin B1
      accumulation, induces aberrant mitotic spindles and apoptosis, presumably due to
      the downregulation of PLK1. Although beta-carboline derivatives have been
      demonstrated to show antitumor activities through multiple mechanisms, our data
      indicate for the first time that their cytotoxicity to tumor cells might be
      attributable to the inhibition of PLK1 as well.

PMID- 19855195
TI  - Using LC3 to monitor autophagy flux in the retinal pigment epithelium.
AB  - Autophagy is a highly conserved housekeeping pathway that plays a critical role
      in the removal of aged or damaged intracellular organelles and their delivery to
      lysosomes for degradation. Autophagy begins with the formation of membranes,
      arising in part from the endoplasmic reticulum, that elongate and fuse engulfing
      cytoplasmic constituents into a classic double-membrane bound nascent
      autophagosome. These early autophagosomes undergo a stepwise maturation process
      to form the late autophagosome or amphisome that ultimately fuses with a
      lysosome. Efficient autophagy is dependent on an equilibrium between the
      formation and elimination of autophagosomes; thus, a deficit in any part of this
      pathway will cause autophagic dysfunction. Autophagy plays a role in aging and
      age-related diseases. However, few studies of autophagy in retinal disease have
      been reported.

PMID- 19855197
TI  - New research on aging minority groups is timely and incorporates state of the art
      methodologies.

PMID- 19855198
TI  - Depression outcome among a biracial sample of depressed urban elders.
AB  - OBJECTIVES: There are a paucity of long-term studies from the United States
      concerning predictors of outcome among depressed older community adults. This
      article examines predictors of depression in a biracial sample of older persons
      in Brooklyn, NY. METHODS: The authors conducted a naturalistic study of 110
      persons aged 55 years and older living in randomly selected block groups who had
      a Center for Epidemiologic Studies-Depression (CES-D) score of > or = 8 at
      baseline. Persons were reassessed on an average of 3 years later. Their mean age
      was 69 years, 52% were women, and 35% were whites, and 65% were blacks, among
      whom 71% were African Caribbeans. Using George's Social Antecedent Model of
      Depression, the authors examined the impact of 13 predictor variables on two
      outcome measures: presence of either subsyndromal or syndromal depression (CES-D
      score > or = 8) and presence of syndromal depression (CES-D score > or = 16). To
      control for design effects, the authors used SUDAAN for the data analysis.
      RESULTS: On follow-up, 82% and 88% of subsyndromally and syndromally depressed
      persons at baseline, respectively, were depressed (CES-D > or = 8). In logistic
      regression, baseline depressive symptoms, baseline anxiety symptoms, greater
      increase in anxiety symptoms during the follow-up period, and higher locus of
      control were predictors of any level of depression. These four variables along
      with greater paranoid ideation and/or psychoses and more reliable social contacts
      were significant predictors of syndromal depression on follow-up. There were no
      inter- or intraracial differences in outcome. CONCLUSION: Depressed community
      elders in Brooklyn have highly unfavorable outcomes. Preventive strategies that
      target at-risk persons-i.e., especially those with baseline subsyndromal
      depression, greater anxiety symptoms, and more paranoid ideation and/or psychoses
      may reduce the development of severe or persistent depression.

PMID- 19855200
TI  - Noninvasive positive pressure ventilation: an ABC approach for advanced nursing
      in emergency departments and acute care settings.
AB  - Noninvasive ventilation has become a widespread tool of treatment and support for
      patients in acute care settings. The treatment is used for various clinical
      conditions, particularly chronic obstructive pulmonary disease and acute
      cardiogenic pulmonary edema. The utilization of a simple nursing care checklist
      allows treatment in a systematic fashion. This article discusses the respiratory
      features of this topic: criteria for noninvasive ventilation, choice of the
      interface for acute clinical conditions, ventilators and modes of ventilation in
      noninvasive ventilation, management of setting parameters, patient/ventilator
      interactions, and monitoring.

PMID- 19855199
TI  - Use of latent variable modeling to delineate psychiatric and cognitive profiles
      in Parkinson disease.
AB  - OBJECTIVES: A range of psychiatric symptoms and cognitive deficits occur in
      Parkinson disease (PD), and symptom overlap and comorbidity complicate the
      classification of nonmotor symptoms. The objective of this study was to use
      analytic-based approaches to classify psychiatric and cognitive symptoms in PD.
      DESIGN: Cross-sectional evaluation of a convenience sample of patients in
      specialty care. SETTING: Two outpatient movement disorders centers at the
      University of Pennsylvania and Philadelphia Veterans Affairs Medical Center.
      PARTICIPANTS: One hundred seventy-seven patients with mild-moderate idiopathic PD
      and without significant global cognitive impairment. MEASUREMENTS: Subjects were
      assessed with an extensive psychiatric, neuropsychological, and neurological
      battery. Latent class analysis (LCA) was used to statistically delineate group
      level symptom profiles across measures of psychiatric and cognitive functioning.
      Predictors of class membership were also examined. RESULTS: Results from the LCA
      indicated that a four-class solution best fit the data. The 32.3% of the sample
      had good psychiatric and normal cognitive functioning, 17.5% had significant
      psychiatric comorbidity but normal cognition, 26.0% had few psychiatric symptoms
      but had poorer cognitive functioning across a range of cognitive domains, and
      24.3% had both significant psychiatric comorbidity and poorer cognitive
      functioning. Age, disease severity, and medication use predicted class
      membership. CONCLUSIONS: LCA delineates four classes of patients in mild-moderate
      PD, three of which experience significant nonmotor impairments and comprise over
      two thirds of patients. Neuropsychiatric symptoms and cognitive deficits follow
      distinct patterns in PD, and further study is needed to determine whether these
      classes are generalizable, stable, predict function, quality of life, and long
      term outcomes and are amenable to treatment at a class level.

PMID- 19855202
TI  - Care of the AIDS patient with Pneumocystis pneumonia.
AB  - Pneumocystis pneumonia and AIDS have been linked together for many years. In the
      1980s and 1990s, these diseases often resulted in admission to the critical care
      unit for many patients. Since the discovery of antiretroviral therapy and
      Pneumocystis prophylaxis, this has been a less frequent occurrence. Knowledge
      about caring for this patient in the critical care unit is often not available.
      Psychological and physiological needs common to this population are different
      from other populations and must be addressed. Pharmacological challenges are
      common and may go unrecognized until complications ensue. This article seeks to
      alleviate some of the mystery associated with these issues.

PMID- 19855205
TI  - Styles and qualities of effective leaders.
AB  - In today's healthcare climate, there is a shortage of nurses and nursing faculty.
      We need effective leaderships to navigate through this crisis. Although all
      nurses are leaders, we must develop the necessary skills to be effective. This
      article will briefly describe a few of the types of leaders, identify the
      essential qualities of an effective leader, and discuss the concept of teaching
      leadership.

PMID- 19855207
TI  - Health information literacy: hardwiring behavior through multilevels of
      instruction and application.
AB  - To produce a healthcare provider who is competent in accessing health
      information, nursing faculty members, in tandem with medical librarians, play a
      crucial role in establishing the knowledge base for student competency in health
      information literacy. The time to prepare nursing students to meet the
      information challenges and opportunities of today's healthcare environment is not
      after graduation, but rather while they are in school. By incorporating health
      information literacy skill building throughout the curriculum, nursing faculty
      members can prepare their students to enter the workforce equipped with the
      skills they need to find, retrieve, appraise, and apply information to their
      clinical practice.

PMID- 19855209
TI  - Continuous lateral rotation therapy for acute hypoxemic respiratory failure: the
      effect of timing.
AB  - Previous studies have indicated a positive impact of continuous lateral
      rotational therapy on nosocomial pneumonia, but have shown mixed results in
      decreasing length of stay or ventilator days. The objective of the study was to
      determine if the use of a continuous lateral rotational therapy protocol would
      decrease mortality and morbidity, mean ventilator days, and/or intensive care
      unit and hospital length of stay in patients with a pulmonary diagnosis. The
      study also analyzed the effect of the lag time to the initiation of therapy.
      Prospectively enrolled subjects receiving continuous lateral rotational therapy
      based on predetermined indications were compared with retrospectively identified
      control subjects who met the same inclusion criteria from a similar time period
      in the previous year. Early initiation of continuous lateral rotational therapy
      resulted in significant decreases in ventilator days and intensive care unit
      length of stay. The therapeutic benefit of continuous lateral rotational therapy
      may be enhanced with early identification and treatment of appropriate patients.

PMID- 19855215
TI  - Preventive medicine for nurses.

PMID- 19855216
TI  - In this issue/abstract thinking: Epigenetics and child and adolescent psychiatry.

PMID- 19855217
TI  - Stranded, part II: Velocardiofacial syndrome, behavioral neurogenetics, and the
      study of developmental psychopathology.

PMID- 19855218
TI  - Should we be rethinking how we assess and manage ADHD?

PMID- 19855219
TI  - The era of affluence and its discontents.

PMID- 19855220
TI  - Challenges and opportunities in bringing new medications to market for pediatric
      patients.

PMID- 19855221
TI  - The MTA at 8.

PMID- 19855222
TI  - The MTA at 8.

PMID- 19855224
TI  - Sensitivity of parent reports in the MTA.

PMID- 19855225
TI  - Enhancing access through TeenScreen.

PMID- 19855228
TI  - Telepsychiatry, public mental health, and the workforce shortage in child and
      adolescent psychiatry.

PMID- 19855229
TI  - Congratulations on the 40th anniversaries of the American Pancreatic Association
      and Japan Pancreas Society.

PMID- 19855230
TI  - 2009 American Pancreatic Association presidential address: on our 40th birthday.

PMID- 19855231
TI  - 40th Anniversary Meeting of the Japan Pancreas Society 2009, presidential
      address: let's celebrate our 40th anniversary and enjoy Hawaii.

PMID- 19855232
TI  - The diagnosis of autoimmune pancreatitis: a Western perspective.

PMID- 19855233
TI  - Minimally invasive techniques in pancreatic necrosis.
AB  - Traditional open surgical necrosectomy for treatment of infected pancreatic
      necrosis is associated with high morbidity and mortality, leading to a shift
      toward minimally invasive endoscopic, radiologic, and laparoscopic approaches.
      Percutaneous drainage is useful as a temporizing method to control sepsis and as
      an adjunctive treatment to surgical intervention. It is limited because of the
      requirement for frequent catheter care and the need for repeated procedures.
      Endoscopic transgastric or transduodenal therapies with endoscopic
      debridement/necrosectomy have recently been described and are highly successful
      in carefully selected patients. It avoids the need for open necrosectomy and can
      be used in poor operative candidates. Laparoscopic necrosectomy is also promising
      for treatment of pancreatic necrosis. However, the need for inducing a
      pneumoperitoneum and the potential risk of infection limit its usefulness in
      patients with critical illness. Retroperitoneal access with a nephroscope is used
      to directly approach the necrosis with complete removal of a sequestrum.
      Retroperitoneal drainage using the delay-until-liquefaction strategy also appears
      to be successful to treat pancreatic necrosis. The anatomic location of the
      necrosis, clinical comorbidities, and operator experience determine the best
      approach for a particular patient. Tertiary care centers with sufficient
      expertise are increasingly using minimally invasive procedures to manage
      pancreatic necrosis.

PMID- 19855234
TI  - Biochemical testing for neuroendocrine tumors.
AB  - In this review, we focus on the use of biochemical markers for the diagnosis of
      neuroendocrine tumors and exclusion of conditions that masquerade as
      neuroendocrine tumors. In addition, we outline the use of biochemical markers for
      follow-up, response to intervention, and determination of prognosis. Previous
      publications have focused only on markers specific to certain tumor types, but
      the uniqueness of this chapter is that it presents a new approach ranging from
      biochemical markers that relate to symptoms to the use of markers that facilitate
      decision making with regard to optimizing the choices of therapy from the complex
      arrays of intervention, The sequence of presentation in this chapter is first to
      provide the usual view, that is, biochemical markers of each tumor type and
      thereafter the diagnosis of the underlying condition or exclusion thereof and
      finally the algorithm for their use from the clinical presentation to the
      suspected diagnosis and the biochemical markers to monitor progression and
      therapeutic choice. There is also a specific description of the properties of the
      most important biochemical markers and 2 complications, bone metastasis and
      carcinoid heart disease, from the biochemical point of view.

PMID- 19855237
TI  - Overcoming Chronic Rejection-Can it B?
AB  - Despite the success of immunosuppressive drug therapy to reduce the incidence of
      acute rejection in organ transplantation, chronic rejection is still an
      impediment to long-term graft survival and tolerance. There is a growing body of
      evidence that B-cell production of alloantibody is an important element in the
      genesis of chronic rejection. Effector function of B cells in transplantation is
      not specifically targeted by current T-cell-directed therapeutic approaches. We
      briefly discuss the origin, animal models, diagnostic methods, and currently
      available B cell reagents that might be used in combination with existing
      immunosuppressive regimens to address B-cell-mediated allograft injury.

PMID- 19855238
TI  - Epidemiology of pretransplant EBV and CMV serostatus in relation to
      posttransplant non-Hodgkin lymphoma.
AB  - BACKGROUND.: Despite the importance of non-Hodgkin lymphoma (NHL) as a
      posttransplant complication, the relationship between NHL and recipient
      seropositivity for Epstein-Barr virus (EBV) or cytomegalovirus (CMV) is
      incompletely understood. METHODS.: Kidney, heart, and liver transplant recipients
      reported to the Collaborative Transplant Study with known pretransplant EBV and
      CMV serostatus were analyzed in terms of clinically manifest NHL. Cox
      multivariate regression analysis was performed to account for a wide range of
      possible confounders. RESULTS.: In total, 18,682 kidney, 2042 heart, and 2616
      liver transplant recipients were analyzed. Regardless of age, pretransplant EBV
      serostatus was significantly associated with risk of NHL in kidney transplant
      recipients (P<0.001). There was no significant difference in lymphoma rates
      according to CMV and CMV serostatus among EBV and EBV recipients (log-rank P=0.55
      and P=0.57, respectively), but hospitalization for CMV disease during year 1
      posttransplant was associated with subsequent NHL (hazard ratio [HR] 6.1; 95%
      confidence interval [CI] 2.0-18.4; P=0.001). EBV serostatus was also associated
      with increased risk of NHL in heart transplant patients (HR 3.6; 95% CI 1.1-11.3;
      P=0.031) but, contrary to expectation, not in liver recipients (HR 0.6; 95% CI
      0.1-1.7; P=0.32). CONCLUSIONS.: In view of the striking increase in risk of NHL
      in EBV kidney transplant recipients of all ages, EBV serostatus should be
      determined pretransplant in all age groups. CMV serostatus was not independently
      associated with risk of NHL after kidney transplantation. Surprisingly, in liver
      transplantation, the risk of NHL was virtually unaffected by EBV serostatus.

PMID- 19855239
TI  - Commentary on "The UK Scheme for a Mandatory Continuous Monitoring of Early
      Transplant Outcome in all Kidney Transplant Centres" by Collett D, Sibanda N,
      Pioh S, Bradley A, and Rudge C.

PMID- 19855240
TI  - The UK scheme for mandatory continuous monitoring of early transplant outcome in
      all kidney transplant centers.
AB  - Mandatory continuous monitoring of early transplant outcome with centralized
      oversight was introduced in 2004 for all 23 UK adult kidney transplant units.
      Risk-adjusted cumulative sum charts are used to assess 30-day graft and patient
      survival against past performance for each center, and change in transplant
      center performance is assessed by tabular cumulative sum charts. The monitoring
      scheme has performed as predicted from simulations used to establish outcome
      thresholds and has been validated by comparison with 1- and 5-year outcome data
      for all UK transplant centers. The value and limitations of the scheme are
      discussed along with changes that may improve its utility as a tool for self
      assessment and central oversight.

PMID- 19855241
TI  - Epstein-barr virus vaccination of transplant candidates: light at the end of the
      tunnel?

PMID- 19855242
TI  - The review by Kwun and Knechtle-"can it B?"-asks whether B cells are responsible
      for chronic rejection of transplants.

PMID- 19855243
TI  - Suppression of hepatocellular carcinoma recurrence after rat liver
      transplantation by FTY720, a sphingosine-1-phosphate analog.
AB  - BACKGROUND.: Although the outcome of liver transplant patients with
      hepatocellular carcinoma (HCC) has improved with the introduction of strict
      criteria, tumor recurrence still remains a significant problem. Sphingosine-1
      phosphate (S1P) is a phospholipid mediator that can induce diverse cellular
      responses, such as proliferation, migration, adhesion, and cell-rounding, in
      cancer cells. We investigated whether FTY720, a S1P analog, suppresses tumor
      recurrence after experimental liver transplantation in a rat HCC model. METHODS.:
      HCC-bearing rats were subjected to orthotropic liver transplantation. HCC cells
      were analyzed for cell migration, proliferation, and S1P receptors. RESULTS.:
      FTY720 induced the down-regulation of the S1P-1 receptor of HCC cells and
      suppressed both cancer cell migration and proliferation. FTY720 also suppressed
      mitogen-activated protein kinase phosphorylation. The suppression of tumor
      recurrence after liver transplantation and a significant prolongation of survival
      were observed in the FTY720-treated rats, in comparison with FTY720-untreated
      rats. CONCLUSION.: FTY720 suppresses the invasiveness and proliferation of HCC
      through a down-regulating S1P-1 receptor to suppress the recurrence of HCC after
      liver transplantation; FTY720 may be used as a new antimetastatic agent for the
      prevention of tumor recurrence after liver transplantation.

PMID- 19855244
TI  - Oleanolic Acid, a plant triterpenoid, significantly improves survival and
      function of islet allograft.
AB  - BACKGROUND.: Oleanolic acid (OA) is a ubiquitous triterpenoid, with potent
      antioxidant and anti-inflammatory properties. Here, we tested whether these
      combined properties of OA can prevent nonimmunologic primary nonfunctioning and
      immunologic phenomena ascribed to graft rejection hence prolong islet allograft
      survival. METHODS.: Islet transplants were performed under kidney capsule of
      streptozotocin-induced diabetic C57BL/6 mice with BALB/c islets. Recipients were
      treated with 0.5 mg/day of OA intraperitoneally, and serum samples were collected
      once in 2 days and used for luminex, ELISA, and donor-specific antibody
      screening. Transplanted mice were killed at different time intervals to obtain
      splenocytes and kidney samples for ELISPOT, mixed leukocyte reaction, and
      immunohistochemical studies. RESULTS.: After transplantation, the decrement of
      blood glucose was significantly faster in mice receiving OA less than 2+/-1 days
      compared with untreated (4+/-2 days). OA prolonged survival of transplanted
      islets up to 23+/-3 days and reversed diabetes even with 250 islets. Treatment
      group showed increased serum interleukin (IL)-10 (twofold) and decreased
      inducible protein-10 and IL-4 (threefold) in luminex. Significantly reduced
      frequency of interferon-gamma (4.5-fold), IL-4 (3.5-fold), IL-2 (2.3-fold), and
      IL-17 (fourfold) producing T-cell populations were found in ELISPOT. OA-treated
      grafts had significant reduced and delayed infiltration of CD4+ and CD8+ T cells.
      OA also delayed donor-specific antibody generation up to 19 days after
      transplantation. Combined treatment with cyclosporine A, OA further prolonged the
      islet allograft survival to 34+/-3 days. CONCLUSIONS.: In conclusion, OA is an
      attractive, dietary nontoxic plant triterpenoid, which suppresses the production
      of proinflammatory cytokines and delays graft-specific immune responses to
      prolong islet allograft survival.

PMID- 19855245
TI  - Chemokine receptor blockade with a synthetic nonpeptide compound attenuates
      cardiac allograft vasculopathy.
AB  - BACKGROUND.: Recruitment of recipient mononuclear cells to the donor heart is a
      central event in the development of cardiac allograft vasculopathy (CAV). The
      role of individual chemokine receptors in this process is incompletely defined.
      TAK-779 (N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten
      8-yl]carbonyl]amino]benzyl]tetra-hydro-2H-pyran-4-aminium chloride) is a
      synthetic nonpeptide antagonist of CCR5 and CXCR3. The purpose of this study is
      to determine if combined CCR5 and CXCR3 blockade by TAK-779 would attenuate CAV
      in an experimental model. METHODS.: We used a previously characterized murine
      model of CAV. Recipient mice were treated with TAK-779 or vehicle control. Donor
      hearts were harvested on day 24 posttransplantation and analyzed for intimal
      thickening and cellular infiltration. Recipient splenocytes were analyzed for
      proliferative response and interferon (IFN)-gamma production by enzyme-linked
      immunosorbent spot assay. The donor hearts were also examined for heme oxygenase
      1 (HO-1) gene induction. RESULTS.: CCR5 and CXCR3 blockade by TAK-779 reduced the
      severity of intimal lesions (53+/-10% vs. 16+/-2%; P<0.05) and decreased the
      number of graft infiltrating CCR5 and CXCR3 CD4 and CD8 lymphocytes. Moreover,
      treatment with TAK-779 (a) decreased alloantigen-specific T-lymphocyte
      proliferation and number of IFN-gamma producing cells and (b) increased HO-1 gene
      transcript level in the allografts. CONCLUSIONS.: Antagonism of CCR5 and CXCR3 by
      TAK-779 is effective in controlling CAV. The beneficial effects of TAK-779 may be
      because of (a) reduction in CCR5 and CXCR3 T-lymphocyte subset infiltration into
      the graft, (b) attenuation of alloantigen-specific T-lymphocyte proliferative
      response and IFN-gamma production, and (c) induction of HO-1 gene. This compound
      may offer a novel approach in clinical management of CAV.

PMID- 19855246
TI  - Monitoring of the immunomodulatory effect of CP-690,550 by analysis of the
      JAK/STAT pathway in kidney transplant patients.
AB  - BACKGROUND.: The small molecule drug CP-690,550 inhibits Janus kinase 3 at
      nanomolar concentrations and has recently been shown to prevent allograft
      rejection in rodents and nonhuman primates. METHODS.: As part of a phase 1
      clinical trial, we investigated the effect of CP-690,550 after 29 days of 30 mg
      twice daily treatment at the cellular level in eight kidney transplant patients
      by studying ex vivo phosphorylation of STAT5 (P-STAT5), the key substrate of
      JAK3. RESULTS.: As determined by quantitative fluorescent western blotting,
      interleukin-2-induced P-STAT5 in YT cells was reduced by a median of 73% (P<0.01)
      in the presence of serum collected on day 29 compared with pretreatment baseline.
      When evaluated by phosphospecific flow cytometry, CP-690,550 also reduced
      interleukin-2-induced P-STAT5 in CD3 (median 20%; P<0.05), CD3CD4 (median 37%;
      P<0.05), and CD3CD8 (median 34%; P<0.01) populations in patient-derived
      peripheral blood mononuclear cells. At the functional level, the inhibitory
      effect of CP-690,550 was confirmed by determining the expression of several STAT5
      targets genes. CONCLUSION.: Analysis of P-STAT5 may, therefore, be used to
      determine the immunomodulatory effect of CP-690,550 at the cellular level in
      transplant patients.

PMID- 19855247
TI  - Prospective observational study of sirolimus as primary immunosuppression after
      renal transplantation.
AB  - BACKGROUND.: Sirolimus (SRL) is an important component of clinical
      immunosuppression in renal transplantation, but few international studies have
      examined how this agent is used in routine practice. METHODS.: Within a large
      prospective pharmacoepidemiological study, 718 de novo renal graft recipients
      treated with SRL in 65 centers in 10 countries were monitored for up to 5 years
      posttransplant to compare the principal outcomes and adverse effects by treatment
      regimen. RESULTS.: Principal treatment regimens were SRL without a calcineurin
      inhibitor (33%), SRL+cyclosporine A (CsA) (33%), and SRL+tacrolimus (TAC) (34%);
      18% of subjects discontinued SRL, 124/718 (17%) developed biopsy-confirmed acute
      rejection (BCAR), 64/718 (9%) lost their graft, and 50/718 (7%) died during
      follow-up. Calculated creatinine clearance was 66+/-26 mL/min at 2 years. The
      most common adverse events were hypertension, hyperlipidemia, anemia, urinary
      tract infections, and diabetes. BCAR was significantly lower in subjects
      receiving SRL+TAC (hazard ratio [HR] 0.46, P=0.009) but not significantly lower
      in those receiving SRL+CsA (HR 0.62, P=0.102) compared with SRL without a
      calcineurin inhibitor. Graft loss or death did not significantly differ between
      treatment groups but were associated, respectively, with deceased donor grafts
      (HR 3.33, P<0.001) and increased age (HR 1.04, P<0.001). No improvement was
      observed in patients receiving mycophenolate mofetil in any treatment combination
      (HR 0.80, P=0.438 for BCAR; HR 0.93, P=0.849 for graft loss; and HR 0.75, P=0.531
      for death). CONCLUSIONS.: SRL is most commonly used in combination with
      mycophenolate mofetil, CsA, or TAC. BCAR was least common in subjects receiving
      SRL+TAC, but other outcomes seemed comparable between the treatment regimens in
      routine practice.

PMID- 19855248
TI  - High risk of graft failure in patients with anti-HLA antibodies undergoing
      haploidentical stem-cell transplantation.
AB  - BACKGROUND.: Although donor-specific anti-human leukocyte antigen (HLA)
      antibodies (DSA) have been implicated in graft rejection in solid organ
      transplantation, their role in hematopoietic stem-cell transplantation remains
      unclear. METHODS.: To address the hypothesis that the presence of DSA contributes
      to the development graft failure, we tested 24 consecutive patients for the
      presence of anti-HLA antibodies determined by a sensitive and specific solid
      phase/single-antigen assay. The study included a total of 28 haploidentical
      transplants, each with 2 to 5 HLA allele mismatches, at a single institution,
      from September 2005 to August 2008. RESULTS.: DSA were detected in five patients
      (21%). Three of four (75%) patients with DSA before the first transplant failed
      to engraft, compared with 1 of 20 (5%) without DSA (P=0.008). All four patients
      who experienced primary graft failure had second haploidentical transplants. One
      patient developed a second graft failure with persistent high DSA levels, whereas
      three engrafted, two of them in the absence of DSA. No other known factors that
      could negatively influence engraftment were associated with the development of
      graft failure in these patients. CONCLUSIONS.: These results suggest that donor
      specific anti-HLA antibodies are associated with a high rate of graft rejection
      in patients undergoing haploidentical stem-cell transplantation. Anti-HLA
      sensitization should be evaluated routinely in hematopoietic stem-cell
      transplantation with HLA mismatched donors.

PMID- 19855250
TI  - Serum adiponectin levels and ambulatory blood pressure monitoring in pediatric
      renal transplant recipients.
AB  - BACKGROUND.: Reduced levels of serum adiponectin, an adipokine, are associated
      with cardiovascular and obesity-related diseases; however, relations between
      adiponectin and hypertension are unclear. METHODS.: This cross-sectional study
      examined adiponectin and ambulatory blood pressure monitoring (ABPM) in 33
      pediatric renal transplant recipients (TXP), aged 8 to 19 years, median of 1.9
      years after transplant. Serum total adiponectin (microg/mL) and high molecular
      weight-to-total adiponectin ratio (HMWr), 24-hr ABPM, and dual x-ray
      absorptiometry measures of fat mass were obtained. RESULTS.: The 12 TXP with
      hypertension (defined as BP index >1.0 and BP load >25%) had lower total
      adiponectin levels (7.4+/-3.2 vs. 10.9+/-5.2 microg/mL, P=0.045) compared with
      nonhypertensive TXP. Hypertensive TXP trended toward lower HMWr compared with
      nonhypertensive TXP (0.40+/-0.09 vs. 0.47+/-0.11, P=0.064). Levels did not differ
      according to sex, obesity or dipper status. In univariate analyses, total
      adiponectin and HMWr were negatively and significantly correlated with indexed BP
      in the daytime, nighttime, and 24-hr periods (R=-0.35 to -0.57). After adjustment
      for estimated glomerular filtration rate, fat mass, anti-hypertensive medication
      and fasting glucose, (1) lower total adiponectin was significantly and
      independently associated with greater elevations in all ABPM indexes except for
      nighttime systolic indexed BP, and (2) HMWr was inversely associated with all
      ABPM indexes. Lower adiponectin levels (P=0.049) and HMWr (P=0.042) were
      associated with greater odds of hypertension. CONCLUSION.: These data indicate
      that lower total adiponectin and HMWr were significantly and independently
      associated with greater ambulatory blood pressure.

PMID- 19855249
TI  - A phase I trial of epstein-barr virus gp350 vaccine for children with chronic
      kidney disease awaiting transplantation.
AB  - BACKGROUND.: Vaccination against Epstein-Barr virus (EBV), inducing an antibody
      response to the envelope glycoprotein gp350, might protect EBV-negative children
      with chronic kidney disease from lymphoproliferative disease after
      transplantation. METHODS.: A phase I trial recruited children with chronic kidney
      disease to two successive cohorts given three injections of 12.5 microg (n=6) and
      25 microg (n=10) recombinant gp350/alhydrogel vaccine over 6 to 8 weeks.
      RESULTS.: One in each cohort acquired wild EBV before the week 28 evaluation.
      Both doses were similarly immunogenic, inducing an IgG response in all 13
      evaluable patients. Neutralizing antibodies were detected in four recipients (1/4
      in the 12.5 microg and 3/9 in the 25 microg cohort). Median time from first
      vaccination to transplantation was 24 weeks. Immune responses declined rapidly
      and were unlikely to affect posttransplant events. DISCUSSION.: The vaccine was
      immunogenic but a prolonged vaccine schedule up to time of transplantation or
      improved adjuvants are required in future trials to reduce posttransplant EBV
      load and risk of lymphoproliferative disease.

PMID- 19855251
TI  - A rare case of obstructive uropathy in renal transplantation: ipsilateral
      indirect inguinal herniation of a transplant ureter.

PMID- 19855252
TI  - Cerebrospinal fluid maraviroc concentrations in HIV-1 infected patients.
AB  - In order to assess the penetration of maraviroc to the central nervous system, we
      measured maraviroc concentrations in cerebrospinal fluid (CSF) and plasma.
      Concentrations were determined by liquid chromatography tandem mass spectrometry
      (lower limit of quantitation 1.25 ng/ml) in seven paired CSF and plasma samples.
      The median plasma maraviroc concentration was 94.9 ng/ml (range 21.4-478.0) and
      the median CSF concentration was 3.63 ng/ml (range 1.83-12.2). CSF samples
      exceeded the median EC90 for maraviroc (0.57 ng/ml) by at least three-fold. The
      CSF levels of maraviroc found in this study likely contribute to viral
      suppression in the CSF.

PMID- 19855254
TI  - A. B. Ackerman's phenomenon: the preacher and the master of dispute.

PMID- 19855253
TI  - Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral
      load in a seroincident cohort of HIV-1-infected individuals.
AB  - OBJECTIVES: Toll-like receptors (TLRs) are innate immune sensors that are
      integral to resisting chronic and opportunistic infections. Mounting evidence
      implicates TLR polymorphisms in susceptibilities to various infectious diseases,
      including HIV-1. We investigated the impact of TLR single nucleotide
      polymorphisms (SNPs) on clinical outcome in a seroincident cohort of HIV-1
      infected volunteers. DESIGN: We analyzed TLR SNPs in 201 antiretroviral treatment
      naive HIV-1-infected volunteers from a longitudinal seroincident cohort with
      regular follow-up intervals (median follow-up 4.2 years, interquartile range
      4.4). Participants were stratified into two groups according to either disease
      progression, defined as peripheral blood CD4(+) T-cell decline over time, or peak
      and setpoint viral load. METHODS: Haplotype tagging SNPs from TLR2, TLR3, TLR4,
      and TLR9 were detected by mass array genotyping, and CD4(+) T-cell counts and
      viral load measurements were determined prior to antiretroviral therapy
      initiation. The association of TLR haplotypes with viral load and rapid
      progression was assessed by multivariate regression models using age and sex as
      covariates. RESULTS: Two TLR4 SNPs in strong linkage disequilibrium [1063 A/G
      (D299G) and 1363 C/T (T399I)] were more frequent among individuals with high peak
      viral load compared with low/moderate peak viral load (odds ratio 6.65, 95%
      confidence interval 2.19-20.46, P < 0.001; adjusted P = 0.002 for 1063 A/G). In
      addition, a TLR9 SNP previously associated with slow progression was found less
      frequently among individuals with high viral setpoint compared with low/moderate
      setpoint (odds ratio 0.29, 95% confidence interval 0.13-0.65, P = 0.003, adjusted
      P = 0.04). CONCLUSION: This study suggests a potentially new role for TLR4
      polymorphisms in HIV-1 peak viral load and confirms a role for TLR9 polymorphisms
      in disease progression.

PMID- 19855255
TI  - Effect of botulinum toxin injection on nocturnal bruxism: a randomized controlled
      trial.
AB  - OBJECTIVE: To evaluate the effect of botulinum toxin type A on nocturnal bruxism.
      DESIGN: Twelve subjects reporting nocturnal bruxism were recruited for a double
      blind, randomized clinical trial. Six bruxers were injected with botulinum toxin
      in both masseters, and six with saline. Nocturnal electromyographic activity was
      recorded in the subject's natural sleeping environment from masseter and
      temporalis muscles before injection, and 4, 8, and 12 wks after injection and
      then used to calculate bruxism events. Bruxism symptoms were investigated using
      questionnaires. RESULTS: Bruxism events in the masseter muscle decreased
      significantly in the botulinum toxin injection group (P = 0.027). In the
      temporalis muscle, bruxism events did not differ between groups or among times.
      Subjective bruxism symptoms decreased in both groups after injection (P < 0.001).
      CONCLUSIONS: Our results suggest that botulinum toxin injection reduced the
      number of bruxism events, most likely mediated its effect through a decrease in
      muscle activity rather than the central nervous system. We controlled for placebo
      effects by randomizing the interventions between groups, obtaining subjective and
      objective outcome measures, using the temporalis muscle as a control, and
      collecting data at three postinjection times. Our controlled study supports the
      use of botulinum toxin injection as an effective treatment for nocturnal bruxism.

PMID- 19855256
TI  - Quality and safety on an acute surgical ward: an exploratory cohort study of
      process and outcome.
AB  - OBJECTIVE: To evaluate patient safety in an emergency surgical unit using process
      and outcome measures in parallel. BACKGROUND: Patient harm from errors in care is
      common in modern surgical practice. Measurement of the problem is essential to
      any solution, but current methods of evaluating patient harm are either
      impractical or inadequate. We have therefore analyzed compliance with safety
      relevant care processes, with the aim of developing a process-based system for
      evaluating ward safety. METHODS: Adverse events (AE), potential adverse events
      (PAE), and 7 safety-relevant processes were measured on a 38-bed surgical
      emergency unit over a 16-week period. AE, PAE, and process measures were studied
      by prospective direct observation in large convenience samples, using objective
      measures. Possible influences on AE and PAE risk were analyzed. RESULTS:
      Compliance with the 7 processes studied ranged from 23% to 89%. The AE and PAE
      rates were 11.9% and 13.8% in a 63% sample of admissions (n = 607). Length of
      stay was significantly associated with both AE (P < 0.001) and PAE (P < 0.001).
      Having an operation was also associated with AE (P = 0.001) but not with PAE. No
      other factors appeared to influence AE/PAE rates. Delays were the commonest
      causes of both AE and PAE. CONCLUSIONS: Compliance with individual care processes
      on a ward with average levels of patient harm is poor. Length of hospital stay
      increases the risk of both AE and PAE, suggesting a system defect. A bundle of
      care processes may be useful for monitoring safety improvement.

PMID- 19855257
TI  - Perioperative mortality for management of hepatic neoplasm: a simple risk score.
AB  - OBJECTIVES: To develop a population-based risk score for stratifying patients by
      risk of in-hospital mortality following procedural intervention for hepatic
      neoplasm. BACKGROUND: There has been growing support for the value of surgical
      management of hepatic neoplastic disease, both primary and metastatic. Advances
      in surgical and ablative technologies have contributed to a decrease in the
      mortality associated with these procedures. However, multiple patient-, disease-
      and treatment-related factors can contribute to perioperative morbidity and
      mortality. METHODS: Using the Nationwide Inpatient Sample from 1998 to 2005, a
      retrospective cohort of patient-discharges for hepatic procedures with a
      concurrent diagnosis of hepatic primary or metastatic neoplasm to the liver was
      assembled. Procedures were categorized as lobectomy, wedge resection, or
      enucleation/ablation. Logistic regression and bootstrap methods were used to
      create an integer score for estimating the risk of in-hospital mortality using
      patient demographics, comorbidities, procedure type, tumor type, and hospital
      characteristics. A randomly selected sample of 80% of the cohort was used to
      create the risk score. Testing was conducted in the remaining 20% validation-set.
      RESULTS: In total, 12,969 patient-discharges were identified. Overall in-hospital
      mortality was 3.45%. Predictive characteristics incorporated into the model
      included: age, sex, Charlson comorbidity score, procedure type, hospital type,
      and type of neoplasm. Integer values were assigned to these, and used to
      calculate an additive score. Five clinically relevant groups were assembled to
      stratify risk, with a 36-fold gradient in mortality. Rates in the groups were as
      follows: 0.9%, 2.5%, 6.8%, 17.6%, and 35.9%. In the derivation set, as well as in
      the validation set, the simple score discriminated well, with c-statistics of
      0.76 and 0.70, respectively. CONCLUSIONS: An integer-based risk score can be used
      to predict in-hospital mortality after hepatic procedure for neoplasm, and may be
      useful for preoperative risk stratification and patient counseling.

PMID- 19855258
TI  - Is portal hypertension a contraindication to hepatic resection?
AB  - BACKGROUND AND AIMS: The outcome of hepatic resection in cirrhotic patients has
      improved remarkably in recent years with improved surgical techniques and
      perioperative care; however, the role of portal hypertension is still uncertain.
      The aim of this study was to elucidate surgical outcomes of hepatectomy in
      patients with portal hypertension. METHODS: Data from 241 cirrhotic patients who
      underwent resection for hepatocellular carcinoma were retrospectively collected
      and analyzed: patients were divided into 2 groups according to the presence (n =
      89) or absence (n = 152) of portal hypertension at the time of surgery. To
      overcome biases owing to the different distribution of covariates throughout the
      2 groups, a one-to-one match was created using propensity score analysis: after
      match, intraoperative, and postoperative course and survival rates were analyzed.
      RESULTS: Patients with portal hypertension experienced worse preoperative liver
      function (mean model for end-stage liver disease [MELD] score, 9.5 +/- 7.8 vs.
      8.4 +/- 1.3; P = 0.001) and survival rates (P = 0.008) in comparison to those
      without portal hypertension: after one-to-one matching, patients with (n = 78)
      and without portal hypertension (n = 78) had the same preoperative
      characteristics and showed the same intraoperative course, postoperative
      occurrence of liver failure, morbidity, length of in-hospital stay and survival
      rates (P = ns in all cases). The only predictors of postoperative liver failure
      were MELD score (P = 0.001) and extent of hepatectomy (P = 0.005). CONCLUSIONS:
      Faced with the same MELD score and extent of hepatectomy planning, presence of
      portal hypertension should not be considered as a contraindication for hepatic
      resection in cirrhotic patients.

PMID- 19855259
TI  - Differential diagnostic and staging accuracies of high resolution
      ultrasonography, endoscopic ultrasonography, and multidetector computed
      tomography for gallbladder polypoid lesions and gallbladder cancer.
AB  - OBJECTIVE: The authors undertook to investigate the diagnostic performance of
      high-resolution ultrasound (HRUS), and to compare the differential diagnostic and
      staging accuracies of endoscopic ultrasonography (EUS), HRUS, and multidetector
      computed tomography for gallbladder (GB) polypoid lesions and GB cancer. SUMMARY
      OF BACKGROUND DATA: Endoscopic ultrasonography was considered the most sensitive
      diagnostic modality for GB polypoid lesions. However, recent technical
      advancements in other image modalities including conventional sonography (US)
      allow the production of comparable images. METHODS: A total of 170 patients, with
      a more than 1-cm sized polypoid GB lesion, and without evidence of definite local
      invasion to adjacent organs during primary screening, were consecutively enrolled
      in this prospective, blind, comparative study. After excluding 26 patients with
      inappropriate medical histories, 144 patients were finally enrolled. All patients
      underwent surgical resection. Clinical diagnoses were compared with
      histopathologic findings by diagnostic modality. RESULTS: Of the 144 patients,
      there were 115 (79.8%) cases of benign GB polypoid lesions and 29 (20.2%) cases
      of GB cancers. Diagnostic sensitivities for malignancy were 90% for HRUS, 86% for
      EUS, and 72% for CT. When evaluating the abilities of these modalities to predict
      GB cancer depth of invasion, we excluded 2 unusual GB malignancies (melanoma and
      lymphoma), HRUS was found to have the highest diagnostic accuracy of 62.9%; EUS
      and CT had accuracies of 55.5% and 44.4%, respectively. CONCLUSIONS: The
      diagnostic accuracies of HRUS and EUS for the differential diagnosis of GB
      polypoid lesions were comparable. In view of patient comfort and no requirement
      for sedation, we consider that HRUS is likely to become an important diagnostic
      modality for the differential diagnosis and staging of GB polypoid lesions and
      early GB cancer.

PMID- 19855260
TI  - Twenty-five-year follow-up for liver resection: the personal series of Dr. Joseph
      G. Fortner.
AB  - BACKGROUND: Liver resection is performed for many types of malignancies. Few
      reports document actual long-term survival. METHODS: Long-term follow-up of a
      series of 548 liver resections performed between 1970 and 1992 was performed and
      is presented. RESULTS: All patients were followed for at least 15 years after
      surgery. Of the 476 cancer patients, the 5-, 10-, 15-, and 20-year survival rates
      were 38%, 25%, 20%, and 17%, respectively. Within this group, 108 and 88 patients
      were actual 10- and 15-year survivors, respectively. Median survival time in
      months varied by tumor type: metastatic neuroendocrine (81 months), biliary
      cancer (cholangiocarcinoma) (63 months), gallbladder cancer (47 months),
      metastatic colorectal cancer (40 months), and hepatocellular carcinoma (27
      months). Survivors of each tumor type living more than 25 years were documented.
      Patients disease-free 10 years after resection for metastatic colorectal cancer
      or gallbladder cancer were usually considered cured. Patients with diagnoses of
      hepatocellular carcinoma, cholangiocarcinoma, or other metastases (including
      neuroendocrine tumors or sarcomas) continued to recur and die of disease.
      CONCLUSION: Liver resection can be performed with long-term survival and
      potential curative outcome in a variety of primary and metastatic cancers of the
      liver.

PMID- 19855261
TI  - Signet ring cell histology is an independent predictor of poor prognosis in
      gastric adenocarcinoma regardless of tumoral clinical presentation.
AB  - OBJECTIVE: To test the hypothesis that signet ring cell (SRC) histology has a
      negative prognostic value in patients with gastric adenocarcinoma (ADC). SUMMARY
      BACKGROUND DATA: In western countries, gastric ADC with SRC often occurs after
      the disease has advanced. Consequently, the prognosis of SRC is generally
      regarded as poor, although survival studies comparing SRC and non-SRC have
      yielded inconsistent results. METHODS: : An intent to treat analysis was
      performed among 215 patients with gastric ADC scheduled for surgical resection
      from 1996 to 2007. Of these, 180 patients underwent the resection and 35 were not
      resected due to diffuse metastatic illness. From 59 resected patients with SRC
      (SRC group), control non-SRC resected patients matched by age, gender, American
      Society of Anaesthesiologists (ASA) classification, tumoral location, and pTNM
      stage were randomly selected by computer (non-SRC group: n = 100) during the same
      study period. RESULTS: The overall median survival was 21 months, which was
      significantly higher in resected compared to non-resected patients (31 vs. 5
      months, P < 0.001). In non-resected patients, SRC histological subtype was
      associated with higher rates of diffuse peritoneal carcinomatosis (90.1% vs.
      62.5%, P = 0.053) and neoplastic ascitis (63.6% vs. 34.7%, P = 0.059) and poorer
      median survival (5 vs. 7 months, P = 0.062). For resected patients, the 2 groups
      (SRC and non-SRC) were comparable regarding matching variables, demographic
      variables, and postoperative course. The median survival was significantly lower
      for SRC patients (21 vs. 44 months, P = 0.004). SRC resected patients exhibited
      higher rates of localized peritoneal carcinomatosis (P = 0.013) and lymph node
      involvement (P < 0.001) at diagnosis, lower R0 resection rate (P = 0.019) and
      earlier tumor relapse (P = 0.009), which was generally in a peritoneal
      carcinomatosis form (P = 0.011). By multivariate analysis, we concluded that SRC
      histology was independently associated with a dismal prognosis after adjustment
      on confounding variables (hazard ratio = 1.5, 95% confidence interval 1.1-2.0, P
      = 0.004). The prognostic role of SRC was maintained after exclusion of patients
      with advanced stage at initial diagnosis such as localized peritoneal
      carcinomatosis or lymph node invasion. CONCLUSIONS: This study is currently the
      best evidence showing that SRC is a major and independent predictor of poor
      prognosis due to specific characteristics such as more infiltrating tumors
      showing affinity for lymphatic tissue accompanied by a higher rate of peritoneal
      carcinomatosis. Our results suggest the need for a specific therapeutic strategy
      for such tumors.

PMID- 19855262
TI  - Trauma-hemorrhage and hypoxia differentially influence kupffer cell phagocytic
      capacity: role of hypoxia-inducible-factor-1alpha and phosphoinositide 3
      kinase/Akt activation.
AB  - OBJECTIVE: We investigated whether Kupffer cell phagocytosis is differentially
      regulated following hypoxia (by breathing hypoxic gas) and trauma-hemorrhage. We
      hypothesized that the differences might result from a differential activation of
      hypoxia-inducible factor (HIF)-1alpha and phosphoinositide 3-kinase (PI3K)/Akt
      pathway under those conditions. BACKGROUND: HIF-1alpha is a biologic O2 sensor
      enabling adaptation to hypoxia. Studies have shown that under hypoxic conditions,
      HIF-1alpha enhances macrophage phagocytosis. Trauma-hemorrhage also produces a
      hypoxic insult with HIF-1alpha activation; however, macrophage phagocytosis is
      suppressed under those conditions. Thus, signaling molecules other than HIF
      1alpha should be taken into consideration in the regulation of macrophage
      phagocytosis following cellular hypoxia or trauma-hemorrhage. METHODS: Male
      C3H/HeN mice were subjected to sham operation, trauma-hemorrhage (laparotomy, 90
      minutes hemorrhagic shock, MAP 35 +/- 5 mm Hg followed by resuscitation) or
      hypoxia (5% O2 for 120 minutes). The trauma-hemorrhage and hypoxia groups
      received Wortmannin (PI3K inhibitor), YC-1 (HIF-1alpha inhibitor) or vehicle at
      the time of maximum bleedout in the trauma-hemorrhage group or at a PaO2 of 30 mm
      Hg during hypoxic air inhalation. Mice were killed 2 hours later and
      samples/cells collected. RESULTS: While the systemic and Kupffer cell hypoxic
      states were similar in the trauma-hemorrhage and hypoxia groups, phagocytic
      capacity was suppressed following trauma-hemorrhage but enhanced in the hypoxia
      group. Kupffer cells from both groups showed increased HIF-1alpha activation,
      which was prevented by Wortmannin or YC-1 treatment. The increase in Kupffer cell
      phagocytosis following hypoxemia was also prevented by Wortmannin or YC-1
      treatment. Akt activation was suppressed in the trauma-hemorrhage group, but
      enhanced in the hypoxia group. Wortmannin and YC-1 treatment prevented the
      increase in Akt activation. CONCLUSIONS: These findings indicate that the
      suppression of Kupffer cell phagocytosis following trauma-hemorrhage is
      independent of cellular hypoxia and activation of HIF-1alpha, but it is possibly
      related to suppression of the Akt activation.

PMID- 19855263
TI  - The usefulness of preoperative dual-phase 99mTc MIBI-scintigraphy and IO-PTH
      assay in the treatment of secondary and tertiary hyperparathyroidism.
AB  - BACKGROUND: Persistent secondary or tertiary hyperparathyroidism (HPT) results
      from failure to remove enough hyperfunctioning parathyroid tissue. Ectopically
      situated parathyroid glands and supernumerary glands make failure more likely.
      Recurrent HPT after subtotal Ptx is usually due to regrowth of the remaining
      parathyroid tissue. Recurrence may also develop from a hyperplastic supernumerary
      gland or rarely from parathyromatosis. Recurrent HPT after total Ptx with
      autotransplantation is usually due to overgrowth of the autograft or for the
      previously mentioned reasons. METHODS: Since 1995, 464 patients with SHPT or THPT
      were treated surgically; intraoperative parathormone (PTH) was measured in 277
      patients. Sixty-eight patients also had a preoperative MIBI scan. We compared the
      preoperative MIBI scan results with intraoperative findings, parathyroid gland
      weight and histology. We questioned whether MIBI uptake corresponded to
      parathyroid gland size and weight. We also correlated the number of Ki67 nuclear
      positive cells with MIBI uptake. For SHPT in group I with 145 patients, neither
      intraoperative PTH (IO-PTH) assay nor MIBI scanning was done. In group II with
      163 patients IO-PTH was used and in group III with 48 patients both IO-PTH and
      MIBI scanning was used. For THPT in group I with 42 patients, neither IO-PTH
      assay nor MIBI scanning was done. In group II with 46 patients IO-PTH was used
      and in group III with 20 patients both IO-PTH and MIBI scanning was used.
      RESULTS: Parathyroid weight correlated directly with MIBI uptake. No correlation,
      however, occurred between MIBI uptake and parathyroid histology or between Ki67
      staining and MIBI scanning. For SHPT in group I the persistence rate was 6.2% and
      recurrence rate 11%; in group II the persistence rate was 4.9% and recurrence
      rate 4.9%; in group III the persistence rate was 2%, and recurrence 4.2% (P <
      0.05 between group I and III for persistence and recurrence). We obtained similar
      results in THPT, but recurrence was 0 in groups II and III, also when only 3
      glands were removed, probably due to asymmetric hyperplasia commonly seen in this
      particular population (P < 0.05 regarding recurrence between group I and II-III,
      no difference between group II and III). CONCLUSION: In conclusion our findings
      support that the surgeon experience is a very important factor for good results
      in patients with SHPT and THPT. Preoperative MIBI scanning and IO-PTH are helpful
      but not essential except in reoperations.

PMID- 19855264
TI  - Communication practices on 4 Harvard surgical services: a surgical safety
      collaborative.
AB  - BACKGROUND: Communication breakdowns between surgical residents and attending
      physicians in the pre- and postoperative setting are common contributors to
      patient injury. These communication transactions might offer an opportunity for
      safety improvement, but it remains unknown how often resident-attending
      communication fails, what the current level of attending involvement is, and how
      often attending input changes the plan for patient care. We conducted a
      prospective study at 4 Harvard teaching hospitals to address these issues.
      METHODS: Three prospective data collection strategies were employed: (1) we
      randomly selected surgical services and queried residents for the occurrence of
      predefined critical patient events and the characteristics of attending
      communications that ensued, (2) on weekends, randomly selected patients were
      interviewed and their charts reviewed to identify the frequency of attending
      visitation and how such visits affected processes of care, and (3) on weekends,
      senior residents on randomly selected surgical services were queried regarding
      the occurrence of attending-resident discussion of patients in their care.
      RESULTS: Of 80 critical patient events identified, 26 (33%) were not communicated
      to attending surgeons. Residents reported that, when contacted, all attending
      physicians were receptive to communication, whether they were the primary surgeon
      or providing cross-coverage. Although residents felt that attending contact was
      unnecessary for safe patient care in 61 (76%) of these events, discussions with
      attending physicians changed management in 33% (18/54) of cases in which they
      occurred. Attending surgeons were found to visit their patients on randomly
      selected weekend days 42% (n = 37) of the time, while 21% (n = 19) had not
      visited for 2 or greater days. When attending physicians visited patients,
      however, resident management was modified 46% (n = 36) of the time. Though
      residents frequently discussed patient management with attending physicians on
      randomly selected weekends, they failed to do so 16% (n = 58) of the time, which
      appeared to be related to service-specific variation (chi = 269, P < 0.0001).
      CONCLUSIONS: In the context of both critical patient events and routine patient
      care, residents often fail to obtain attending surgeons' input for management
      decisions. These failures seem to derive more from residents' perception of
      necessity than from attending physicians' receptiveness or interest in being
      contacted. Once involved, attending physicians frequently modify resident's
      management decisions. It seems, therefore, that there is significant potential
      for communication failure and information loss among our 4 institutions.

PMID- 19855265
TI  - Surgeons' volume of colorectal cancer procedures and collaborative decision
      making about adjuvant therapies.
AB  - BACKGROUND: Few studies have assessed associations of surgeons' practice volume
      with processes of care that lead to better outcomes. OBJECTIVE: We surveyed
      surgeons treating colorectal cancer to determine whether high-volume surgeons
      were more likely to collaborate with other physicians in decisions about adjuvant
      therapies. SUBJECTS AND METHODS: Surgeons caring for patients with colorectal
      cancer in multiple regions and health-care organizations were surveyed to assess
      their volume of colorectal cancer resections and participation in decisions about
      adjuvant chemotherapy and radiation therapy. We used logistic regression to
      assess physician and practice characteristics associated with surgical volume and
      the relation of surgical volume and these other characteristics to collaborative
      decision-making regarding adjuvant therapies. RESULTS: Of 635 responding
      surgeons, those who identified themselves as surgical oncologists or colorectal
      surgeons were more likely than others to report high volume of colorectal cancer
      resections (P < 0.001), as were those who practiced at a comprehensive cancer
      center (P = 0.06) and attended tumor board meetings weekly (vs. quarterly or
      less, P = 0.09). Most surgeons reported a collaborative role in decisions about
      chemotherapy and radiation therapy. However, in adjusted analyses, higher-volume
      surgeons more often reported a collaborative role with other physicians in
      decisions about chemotherapy (P < 0.001) and radiation therapy (P < 0.001).
      CONCLUSIONS: Higher-volume surgeons are more likely to report collaborating with
      other physicians in decisions about adjuvant therapies for patients following
      colorectal cancer surgery. This collaborative decision-making of higher-volume
      surgeons may contribute to outcome differences by surgeon volume.

PMID- 19855266
TI  - Serial change in platelet activation markers with aspirin and clopidogrel after
      acute ischemic stroke.
AB  - OBJECTIVES: Antiplatelet drugs are widely used for secondary prevention after
      cerebral ischemia of noncardioembolic origin and different antiplatelet drugs
      exert different pharmacologic effects. This study investigated differences in
      platelet activation markers in patients taking either aspirin or clopidogrel
      after acute ischemic stroke. METHODS: A prospective randomized case-control study
      evaluated 70 patients with noncardioembolic stroke treated with either aspirin
      (100 mg/d) or clopidogrel (75 mg/d) after acute ischemic stroke. Platelet
      activation markers (CD62P, CD63, and CD40L) were measured by flow cytometry at
      different time points (<48 hours and days 7, 30, and 90 after stroke). The
      markers were also evaluated in 30 at-risk control subjects. RESULTS: Ischemic
      stroke patients had significantly increased circulating CD62P, CD63, and CD40L in
      the acute stage compared with the control group. Levels of CD62P, CD63, and CD40L
      were more significantly reduced in the clopidogrel group than in the aspirin
      group in the first week after stroke. Furthermore, differences in CD62P and CD63
      levels were significant even at 1 month after stroke. CONCLUSIONS: Patients
      treated with clopidogrel have lower platelet activity than those taking aspirin
      after acute ischemic stroke. The stronger effect of clopidogrel is notable 1 week
      after stroke and persists for at least 1 month. Further large-scale trials are
      warranted to clarify optimal treatment.

PMID- 19855268
TI  - Levodopa-induced dyskinesias in Parkinson disease are independent of the extent
      of striatal dopaminergic denervation: a pharmacological and SPECT study.
AB  - The physiopathology of levodopa-induced dyskinesias (LIDs) is unclear.
      Presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms may be
      involved. We have analyzed several clinical and pharmacological parameters, as
      well as the status of the presynaptic dopamine nigrostriatal pathway by using
      DaTSCAN, in 14 patients with Parkinson disease who developed early and severe LID
      despite using low doses of levodopa and 10 patients without this complication
      despite the use of high levodopa doses. Patients were matched for age at onset,
      duration, and severity of Parkinson disease. Statistically significant
      differences were observed only in the duration of LID during the levodopa
      challenge. However, clear differences were also observed in weight and sex
      distribution (women with low weight predominate in the group with dyskinesia),
      severity and duration of LID, and total levodopa dosage. The pattern of response
      to levodopa and the uptake of (123I)N-w-fluoropropyl-2[beta]-carbomethoxy-3[beta]
      (4-iodophenyl)nortropane were similar in both groups. These results indicate that
      the development of LID needs additional contributions beyond nigrostriatal
      denervation. Factors related to sex and body weight could play an important role.
      However, these findings should be considered cautiously because of the limited
      statistical power of the study.

PMID- 19855267
TI  - Orally disintegrating selegiline in Parkinson patients with dopamine agonist
      related adverse effects.
AB  - OBJECTIVE: To determine whether adding orally disintegrating selegiline (ODS)
      while decreasing dopamine agonist (DA) dosages would reduce DA-related adverse
      effects (AEs) of excessive daytime sleepiness (EDS), pedal edema, hallucinations,
      and impulse control disorders (ICDs) without compromising efficacy in Parkinson
      disease (PD) patients. METHODS: This was a 12-week open-label study of 60 PD
      patients with motor fluctuations and DA-related AEs of EDS, pedal edema,
      hallucinations, and ICDs. Orally disintegrating selegiline was initiated at 1.25
      mg once daily, and down titration of the DA was started with a goal of a 50%
      reduction by 1 week. At week 6, ODS was increased to 2.5 mg, and further
      reductions of the DA were allowed if the AEs were not resolved. RESULTS: The
      addition of ODS allowed a reduction in the mean daily dose of pramipexole from
      2.3 to 0.5 mg and immediate-release ropinirole from 11.2 to 2.9 mg. Most subjects
      reported a reduction or resolution of DA-related AEs; 94% with EDS (n = 50), 73%
      with pedal edema (n = 26), 86% with hallucinations (n = 15), and 84% with ICDs (n
      = 25). Mean activities of daily living and motor scores from the Unified
      Parkinson's Disease Rating Scale as well as quality-of-life scores were
      significantly improved without an increase in daily "off" time. The most common
      AEs, most of which resolved after titration, were worsening of PD,
      nausea/vomiting, dyskinesia, increased off time, body aches, insomnia,
      orthostatic hypotension, and increased anxiety and depression. CONCLUSIONS: In
      most subjects, the addition of ODS with decreasing dosages of DAs substantially
      reduced EDS, pedal edema, hallucinations, and ICDs without compromising efficacy.

PMID- 19855269
TI  - High-sensitivity C-reactive protein and plaque composition in patients with
      stable angina pectoris: a virtual histology intravascular ultrasound study.
AB  - OBJECTIVE: Elevated high-sensitivity C-reactive protein (hs-CRP) is related to
      clinical outcome in coronary artery disease. We used virtual histology
      intravascular ultrasound to evaluate the relationship between serum hs-CRP level
      and coronary plaque composition in patients with stable angina pectoris. METHODS
      AND RESULTS: Overall 113 consecutive patients with stable angina pectoris who had
      a de-novo culprit lesion were examined in this study. Patients were divided into
      an elevated hs-CRP group (>3 mg/l; n=40) or a normal hs-CRP group (n=73).
      Grayscale and virtual histology intravascular ultrasound analysis was performed
      across the entire culprit lesion. Mean plaque area was similar in both groups.
      Lesion length (18+/-5 vs. 16+/-6 mm, P<0.046) was significantly greater in the
      elevated hs-CRP group than that in the normal hs-CRP group. Although the
      percentage of dense calcium, fibrofatty tissue, and fibrous tissue was not
      different between the two groups, the percentage of necrotic core was
      significantly greater in the elevated hs-CRP group compared with the normal hs
      CRP group (20+/-9 vs. 16+/-8%, P=0.014). The percentage of necrotic core was
      positively correlated with the serum hs-CRP level (r=0.20, P=0.037). A
      multivariate logistic regression model showed that the percentage of necrotic
      core was associated with elevated hs-CRP (P=0.019; odds ratio=1.1; 95% confidence
      interval=1.01-1.12). CONCLUSION: Elevated hs-CRP was related to the amount of
      necrotic core in the culprit lesion of stable angina pectoris. Our results
      suggest that elevated hs-CRP might reflect the inflammatory activity of the
      coronary atherosclerotic plaque even in the setting of stable angina pectoris.

PMID- 19855271
TI  - Physician communication with families in the ICU: evidence-based strategies for
      improvement.
AB  - PURPOSE OF REVIEW: Skilled physician-family communication in the ICU has been
      shown to improve patient outcomes, but until now little attention has been given
      to the effect of communication on family satisfaction and bereavement outcomes.
      The aim of this review is to outline the recent evidence that effective physician
      communication with families, and proactive palliative care interventions, can
      improve outcomes for both patients and family members in the ICU. RECENT
      FINDINGS: New data from the ICU correlates physician ability to identify and
      respond to emotion and to effectively share prognostic information with improved
      outcomes. Furthermore, proactive palliative care interventions that promote
      family meetings, use of empathic communication skills, and targeted palliative
      care consultations can improve family satisfaction, reduce length of stay in the
      ICU and reduce adverse family bereavement outcomes. SUMMARY: Empathic
      communication, skilful discussion of prognosis, and effective shared decision
      making are core elements of quality care in the ICU, represent basic competencies
      for the ICU physician, and should be emphasized in future educational and
      clinical interventions.

PMID- 19855270
TI  - Prerenal failure: from old concepts to new paradigms.
AB  - PURPOSE OF REVIEW: Prerenal failure is used to designate a reversible form of
      acute renal dysfunction. However, the terminology encompasses several different
      conditions that vary considerably. The lack of a widely accepted definition for
      prerenal failure makes it impossible to determine the epidemiology, natural
      history, and association with adverse outcomes. RECENT FINDINGS: New diagnostic
      and staging criteria for acute kidney injury proposed by the Acute Kidney Injury
      (AKI) Network recognize that small increases in serum creatinine are associated
      with increased mortality. However, these criteria have not determined specific
      diagnostic criteria to classify prerenal conditions. As a consequence of the lack
      of standardized definitions and the difficulty in assessing reversibility of AKI,
      the concept of prerenal failure has been recently challenged. The difference in
      the pathophysiology and manifestations of prerenal failure suggests that our
      current approach needs to be reevaluated. SUMMARY: Prerenal failure state needs
      to be classified depending on the underlying capacity for compensation, the
      nature and the timing of the insult and the adaptation to chronic comorbidities.
      Identification of high-risk states and high-risk processes associated with the
      use of new biomarkers for AKI will provide new tools to distinguish between the
      prerenal failure and the established AKI. This review provides an appraisal of
      the current status and recommendations for future research in this field.

PMID- 19855272
TI  - Using serial severity scores to predict death in ICU patients: a validation study
      and review of the literature.
AB  - PURPOSE OF REVIEW: The present study describes the use of serial severity scores
      to predict death in ICU patients and compares the results with previously
      published literature on this topic. RECENT FINDINGS: Predicting mortality in
      critically ill patients has tremendous significance and methods to do so
      accurately have been studied for decades. The ability to accurately predict death
      impacts medical therapies, triaging, end-of-life care, and many other aspects of
      ICU care. There are many methods in existence to help physicians predict
      mortality, but most are not very accurate on an individual basis. The main tools
      available are severity scores, published outcomes data, and personal experience
      and all of them have significant limitations. One strategy that has been shown to
      be effective in accurately predicting death is to use serial severity scoring
      during the patient's ICU admission. Recently, a retrospective study done on a
      large cohort of ICU patients at a single institution showed very high specificity
      in predicting death by using serial acute physiology, age, and chronic health
      evaluation (APACHE III) scores on days 1 and 3. The authors of this article
      sought to validate this study in a different institution using a slightly
      different model that was easier to use and might increase sensitivity. The
      results of this small study are presented with a review of the literature on the
      use of serial scores to predict death in ICU patients. SUMMARY: Over the years
      multiple studies have shown that systems using serial severity scores can predict
      death in ICU patients with very high but not perfect accuracy. The clinical use
      of these systems remains low however and ultimately their main utility may be in
      research.

PMID- 19855273
TI  - Gastrointestinal regulatory peptides and their effects on fat tissue.
AB  - PURPOSE OF REVIEW: Regulation of body weight, food intake and appetite is complex
      and the gastrointestinal tract represents a central organ participating in the
      regulation of energy homeostasis by signaling to other tissues relevant in this
      context. This update will provide information regarding recent advances in the
      understanding of the interaction of gastrointestinal peptides with adipocytes in
      fat tissue and which biological effects they may exert. RECENT FINDINGS: Several
      gastrointestinal peptides signal to their functional cognate receptors on
      adipocytes in white adipose tissue (WAT) thereby regulating glucose homeostasis,
      lipogenesis, lipolysis, free fatty acid release and may also participate in
      adipocyte differentiation. SUMMARY: Gastrointestinal peptides emanate from
      enteroendocrine cells in the luminal digestive tract and are critical regulators
      of energy homeostasis, food intake and appetite. Recent studies have identified
      that gastrointestinal peptides communicate with WAT and exert their biological
      effects on fat cells. Fundamental understanding of gastrointestinal peptides and
      their interaction with adipocytes will provide future insights for the
      development of pharmacological targets in the treatment of obesity and insulin
      resistant states.

PMID- 19855274
TI  - Gastrointestinal peptides and regulation of gastric acid secretion.
AB  - PURPOSE OF REVIEW: Update on the role of gastrointestinal peptides in regulating
      gastric acid secretion. RECENT FINDINGS: A novel transgenic mouse that expresses
      the entire human gastrin gene locus in G-cells of gastrin-null mice will
      facilitate investigation of gastrin gene regulatory elements. Isolation of a
      highly homogeneous population of G-cells permits the elucidation of stimulatory
      and inhibitory ligands without the confounding presence of other neuroendocrine
      cells. The use of somatostatin receptor knockout mice demonstrated the plasticity
      of gastric acid regulatory mechanisms and compensation by upregulation of the
      galanin pathway which inhibits secretion by enterochromaffin-like cells. The
      importance of adenosine in regulating somatostatin release was shown using
      adenosine receptor knockout mice. SUMMARY: The importance of gastrointestinal
      peptides for regulating gastric acid is evident. Ongoing investigations will
      characterize the mechanisms underlying actions of these agents on gastric acid
      secretion, particularly with regard to their combinatorial effects and interplay
      with other acid-regulating pathways.

PMID- 19855275
TI  - Healthcare reform and women's health.

PMID- 19855276
TI  - Postpartum pelvic floor trauma.
AB  - PURPOSE OF REVIEW: There is strong epidemiological evidence linking vaginal
      childbirth and the development of postpartum incontinence and prolapse. This
      article examines possible mechanisms of pelvic floor damage related to delivery
      and their possible consequences. RECENT FINDINGS: Histology, imaging and
      physiology studies have revealed that vaginal delivery results in direct pelvic
      muscle trauma, disruption of fascial supports and pudendal nerve injury. SUMMARY:
      Epidemiology studies implicate parity and childbirth in the development of
      incontinence and prolapse; however, despite imaging and functional studies
      revealing damage to the pelvic floor muscles, nerves and fascial supports, it is
      unclear what the clinical significance of these findings is. In addition, the
      effect of mode of delivery is uncertain, and although cesarean section reduces
      the risk of pelvic floor trauma, it is not entirely protective. Further research
      is required into the effect of pregnancy on pelvic floor dysfunction and the
      effect of mode of delivery.

PMID- 19855277
TI  - Update on pediatric cataract surgery and intraocular lens implantation.
AB  - PURPOSE OF REVIEW: Cataract surgery is the most commonly performed intraocular
      surgery in the pediatric population worldwide. Although the basic surgical
      techniques have not significantly changed over the last several years, there are
      many related issues under continual debate and research. These include use of
      local perioperative anesthesia, capsular management, type and power of
      intraocular lenses (IOLs), sutured IOLs, and risk of subsequent glaucoma. This
      review will primarily focus on postsurgical outcomes and IOL-related
      controversies. RECENT FINDINGS: The just completed Infant Aphakia Treatment Study
      aims to answer questions regarding visual outcomes with primary IOL implantation
      versus contact lens use in children less than 7 months old with a unilateral
      congenital cataract. But correct IOL selection is controversial as recent studies
      highlight difficulties with biometry measurement and IOL calculations in the
      entire pediatric population. We also discuss the risk of late suture breakage and
      dislocation with sutured IOLs and the risks of aphakic glaucoma. SUMMARY:
      Worldwide experiences with pediatric cataract surgery and IOL implantation are
      constantly evolving. Expectations of good outcomes by the patients, families, and
      surgeons are also increasing therefore continued efforts to improve techniques
      and formulas specific to the pediatric population are critical.

PMID- 19855278
TI  - Cataract surgery after pars plana vitrectomy.
AB  - PURPOSE OF REVIEW: To review recent studies and advances and their possible
      implications in the care of patients undergoing cataract surgery after pars plana
      vitrectomy. RECENT FINDINGS: Optical biometry has shown to be superior to
      ultrasound biometry in vitrectomized eyes but still not achieving as good results
      as it does in nonvitrectomized eyes. Blue light-filter intraocular lenses, with
      their possible advantage of macular protection, have shown no operative or
      functional disadvantages in vitrectomized eyes, and thus their routine use can be
      justified. However, presbyopia-correcting intraocular lenses, at least at their
      current stage of development, generally, are still not accepted for vitrectomized
      eyes. Combining cataract surgery with intravitreal injections of bevacizumab or
      triamcinolone acetonide in patients with macular edema and cataract is advisable
      to avoid exacerbation of the condition and improve visual outcome. Despite the
      recent advances, incidences of posterior capsular opacification and retinal
      detachment are still considerable. SUMMARY: Understanding ocular anatomical
      alterations imposed by the previous pars plana vitrectomy surgery and the
      underlying vitreoretinal disease will allow the surgeon to address the special
      challenges. Despite that, recent advances in techniques and instrumentation have
      improved the surgical safety and outcomes, reported complications rates are still
      relatively high.

PMID- 19855279
TI  - Converting human pluripotent stem cells into beta-cells: recent advances and
      future challenges.
AB  - PURPOSE OF REVIEW: The transplantation of insulin-producing beta-cells derived
      from human embryonic stem cells and induced pluripotent stem cells (collectively
      termed pluripotent stem cells or PSCs) holds great promise for therapy of
      diabetes mellitus. The purpose of this review is to summarize recent advances in
      this area, emphasizing the importance of studies of endocrine pancreas
      development in efforts to direct PSC differentiation into endocrine cells, as
      well as to outline the major challenges remaining before transplantation of PSC
      derived beta-cells can become a reality. RECENT FINDINGS: Although several
      protocols to generate glucose-responsive pancreatic beta-cells in vitro have been
      described, the most successful approaches are those that most closely mimic
      embryonic development of the endocrine pancreas. Until recently, cells generated
      by these methods have exhibited immature pancreatic endocrine phenotypes.
      However, protocols that generate more functional beta-like cells have now been
      described. In addition, small molecules are being used to improve protocols to
      direct differentiation of PSCs into endoderm and pancreatic lineages. SUMMARY:
      Advances over the last decade suggest that generating functional beta-cells from
      human PSCs is achievable. However, there are aspects of beta-cell development
      that are not well understood and are hampering generation of PSC-derived beta
      cells. In particular, the signaling pathways that instruct endocrine progenitor
      cells to differentiate into mature and functional beta-cells are poorly
      understood. Other significant obstacles remain, including the need for safe and
      cost-effective differentiation methods for large-scale generation of
      transplantation quality beta-cells, methods to prevent immune rejection of
      grafted tissues, and amelioration of the risks of tumorigenesis.

PMID- 19855281
TI  - Forensic emergency medicine: old wine in new barrels.
AB  - Emergency and forensic physicians may find themselves sometimes on the same
      medical battleground but with different primary aims and hence often ignore or do
      not recognize each other's needs. The emergency physician interacts with law
      enforcement agencies with greater frequency than any other hospital physician and
      hence needs expertise with legal issues. Awareness of the forensic relevance of
      certain medical observations by emergency physicians, knowledge of emergency
      medicine methodology and techniques and of resuscitation-related injuries by
      forensic physicians may lead to a higher standard in both forensic and emergency
      medicine, a better serving of the criminal justice system, and most importantly
      safeguarding the rights of victims of criminal assault. It is this achievable
      mutual symbiosis that we would like to refer to as the concept of 'forensic
      emergency medicine'.

PMID- 19855282
TI  - Recurrent respiratory papillomatosis presenting to an emergency department.
AB  - Recurrent respiratory papillomatosis is a rare but important cause of stridor in
      children presenting to the emergency department. Delayed diagnosis makes
      treatment more difficult and can lead to critical upper-airway obstruction. This
      case report illustrates the typical presenting features of the disease in a 3
      year-old child.

PMID- 19855280
TI  - Inducible pluripotent stem cells: not quite ready for prime time?
AB  - PURPOSE OF REVIEW: Inducible pluripotent stem (iPS) cells derived from somatic
      cells represent a novel renewable source of tissue precursors. The potential of
      iPS cells is considered to be at least equivalent to that of human embryonic stem
      cells, facilitating the treatment or cure of diseases such as diabetes mellitus,
      spinal cord injuries, cardiovascular disease, and neurodegenerative diseases, but
      with the potential added benefit of evading the adaptive immune response that
      otherwise limits allogeneic cell-based therapies. This review discusses recent
      advances in pluripotency induction and the use of iPS cells to produce
      differentiated cells, while highlighting roadblocks to the widespread use of this
      technology in the clinical arena. RECENT FINDINGS: Whereas ethical and safety
      issues surrounding the use of human embryonic stem cells for the treatment of
      disease continue to be debated, use of iPS cells may be viewed as a more widely
      acceptable compromise. Since the first descriptions of inducible pluripotency
      from somatic cells, multiple laboratories have collectively made tremendous
      strides both in developing alternative, more clinically acceptable, induction
      strategies and in demonstrating the proof-of-principle that iPS cells can be
      differentiated into a variety of cell types to reverse mouse models of human
      disease. SUMMARY: Although the prospect of using patient-specific iPS cells has
      much appeal from an ethical and immunologic perspective, the limitations of the
      technology from the standpoint of reprogramming efficiency and therapeutic safety
      necessitate much more in-depth research before the initiation of human clinical
      trials.

PMID- 19855284
TI  - Granulocytapheresis in the treatment of severe alcoholic hepatitis: a case
      series.
AB  - OBJECTIVES: The management of alcoholic hepatitis remains controversial. Anti
      tumour necrosis factor treatments have been studied recently. We piloted the use
      of granulocytapheresis (GCAP) in the management of severe alcoholic hepatitis.
      METHODS: GCAP was performed on six patients with severe alcoholic hepatitis.
      Their clinical and laboratory progress was reviewed retrospectively. RESULTS: Six
      of the patients underwent at least one session of GCAP. Three of the patients had
      coexistent renal failure and five of the six patients were corticosteroid
      nonresponders. All patients tolerated the procedure. However, three of the
      patients died during their hospital admission within 4 days of GCAP treatment.
      These three patients suffered from torrential variceal haemorrhage, multiorgan
      failure and pneumonia, respectively. Two patients died 18 and 25 days after their
      GCAP treatment, both with multiorgan failure. The survivor was the sole
      corticosteroid responder of the group. There was a trend towards a fall in serum
      bilirubin level after GCAP, but this did not reach significance. CONCLUSION: GCAP
      is tolerated in severe alcoholic hepatitis; however, we have no evidence of
      survival advantage with this treatment.

PMID- 19855283
TI  - Transient elastography assessment of the liver stiffness dynamics during acute
      hepatitis B.
AB  - BACKGROUND AND AIMS: The diagnostic accuracy of transient elastography (TE) for
      assessment of hepatic fibrosis is hampered by several factors, including acute
      parenchymal injury. Evaluation of liver stiffness (LS) using TE during acute
      hepatitis B may help to assess chronic hepatitis B patients with flares. PATIENTS
      AND METHODS: Twelve patients consecutively referred for acute hepatitis B,
      underwent sequential examinations with TE and laboratory examinations for 24
      weeks. RESULTS: On admission, aminotransferase ranged from 487 to 6067 IU/l
      (median=2590 IU/l) and LS ranged from 7.1 to 57 kPa (median=15.6 kPa) with nine
      (75%) patients showing LS greater than 11.9 kPa, that is, the predictive cutoff
      for cirrhosis. LS levels correlated significantly with bilirubin, only (r=0.58,
      P<0.05). During follow-up, LS declined from 15.6 to 5.2 kPa at week 24, with a
      significant reduction being observed at week 2 for aminotransferase (from 2590 to
      452 IU/l, P<0.0001) and at week 6 for both LS (from 15.6 to 6.0 kPa, P=0.008) and
      bilirubin (from 10.7 to 0.95 mg/dl, P<0.01). Median decline of LS significantly
      correlated with bilirubin decline (rs=0.70, P<0.05). At week 24, 10 (83%)
      patients showed LS of less than 7.9 kPa and two (17%) patients had LS values
      between 7.9 and 11.9 kPa, including the only patient who developed chronic
      hepatitis B. CONCLUSION: In patients with acute hepatitis B, the initial high
      values of LS mimicking LS cutoff of cirrhosis, likely reflect the liver cell
      inflammation, oedema and swelling as they progressively taper down during
      hepatitis resolution.

PMID- 19855286
TI  - HIV-1 incidence rates and risk factors in agricultural workers and dependents in
      rural Kenya: 36-month follow-up of the Kericho HIV cohort study.
AB  - BACKGROUND: Incidence data from prospective cohort studies using rigorous
      laboratory methods are important in designing and evaluating HIV vaccine and
      therapeutic clinical trials and health care programs. We report 36-month HIV-1
      incidence rates and demographic and psychosocial risks from the Kericho cohort in
      rural Kenya's southern Rift Valley Province. METHODS: Thirty-six month,
      prospective, closed, observational cohort study of adult plantation workers and
      dependents followed biannually. HIV-1 incidence rates per 100 person-years (py)
      were calculated, and Cox regression analyses were used to estimate hazards ratios
      (HR) associated with seroconversion. RESULTS: Two thousand four hundred
      volunteers (mean age +/- SD = 30.1 +/- 8.5 years; 36.5% women) participated.
      Twenty-nine new HIV cases were identified in year 1 of follow-up, which increased
      to cumulative totals of 49 and 63 cases in years 2 and 3, respectively. The
      corresponding 1-, 2-, and 3-year incidence rates were 1.41 [95% confidence
      interval (CI) = 0.95-2.02], 1.16 (95% CI = 0.86-1.54), and 1.00 (95% CI = 0.77
      1.28) per 100 py. Risk factors associated with HIV seroconversion included the
      following: of the Luo tribe (HR = 3.31; 95% CI = 1.65-6.63), marriage more than
      once (HR = 2.83; 95% CI = 1.20-6.69), self-reported male circumcision (HR = 0.32;
      95% CI = 0.17-0.60), history of sexually transmitted infection (HR = 2.40; 95% CI
      = 1.09-5.26), history of substance abuse during sex (HR = 2.44; 95% CI = 1.16
      5.13), and history of transactional sex (HR = 3.30; 95% CI = 1.79-6.09).
      CONCLUSIONS: HIV-1 incidence rates were relatively low in adult plantation
      workers and dependents in rural Kenya. Cohorts including higher risk populations
      (eg, commercial sex workers) warrant consideration for regional HIV preventive
      vaccine trials. Even low incidence, well-described cohorts generate valuable
      epidemiological clinical trial data.

PMID- 19855287
TI  - Evaluation of scanning protocols for imaging the anterior chamber angle with
      anterior segment-optical coherence tomography.
AB  - PURPOSE: To evaluate different anterior segment-optical coherence tomography (AS
      OCT) scanning protocols for detecting eyes with angle closure. METHODS: This
      cross-sectional study enrolled 2104 subjects from a community clinic in
      Singapore. All participants underwent AS-OCT imaging in the dark (Visante, Carl
      Zeiss, Meditec, Dublin, CA), and gonioscopy with a Goldmann 2-mirror and a
      Sussman lens by an experienced examiner. The anterior chamber angle in a
      particular quadrant was considered closed on gonioscopy if the posterior
      trabecular meshwork could not be seen; and on AS-OCT by the presence of contact
      between the iris and angle wall anterior to the scleral spur. Protocols using
      combinations of AS-OCT scans of different quadrants of the eye were compared.
      RESULTS: A total of 1853/2104 right eyes could be graded in all 4 quadrants. In
      all, 380 (20.5%) eyes had closed angles in at least 2 quadrants on gonioscopy.
      The AS-OCT scanning protocol that only imaged the inferior quadrant showed the
      best area under the receiving operating characteristic curve (AUC 0.76,
      sensitivity 84%, specificity 69%) for detecting angle closure. Although
      technically easier to obtain, the protocol that only included the nasal-temporal
      quadrants had the lowest AUC (AUC 0.67, sensitivity 47%, specificity 88%),
      whereas scanning the superior-inferior quadrants showed high sensitivity for
      detecting angle closure (92%), but low specificity (54%). CONCLUSIONS: Using the
      results obtained in a research setting, the diagnostic performance of AS-OCT
      varied according to the adopted scanning protocol. The inferior quadrant-only
      protocol showed the best diagnostic performance but the low specificity would
      limit its use for population screening.

PMID- 19855288
TI  - Three-dimensional high-speed optical coherence tomography for diagnosis of
      hypotony maculopathy after glaucoma filtration surgery.
AB  - PURPOSE: To describe the clinical findings of hypotony maculopathy using 3
      dimensional (3D) topography maps reconstructed from spectral domain optical
      coherence tomography (SD-OCT) imaging, and compare SD-OCT with time domain OCT
      (TD-OCT) for hypotony maculopathy diagnosis. METHODS: This was an observational
      noncomparative case series comprising 7 patients with hypotony maculopathy after
      trabeculectomy with mitomycin-C. All patients underwent consecutive imaging with
      TD-OCT (Stratus OCT) and SD-OCT using various high-resolution instruments. 3-D
      surface maps obtained using SD-OCT were compared with linear scans obtained using
      TD-OCT. RESULTS: Two of 7 eyes had minimally detectable folds with TD-OCT imaging
      in the vertical axis. Five eyes did not show folds on TD-OCT. 3-D topographic
      maps using SD-OCT demonstrated advanced retinal and subretinal folds throughout
      the macular region in all 7 patients. All eyes (4 cases) with no topographically
      detectable folds using SD-OCT within the foveal avascular zone had visual acuity
      of 20/25 or better. Three eyes with obvious contour disruption within the foveal
      pit had visual acuity ranging from 20/30 to 20/70. CONCLUSIONS: SD-OCT using 3-D
      surface topography mapping provides greater sensitivity for hypotony maculopathy
      diagnosis and monitoring as compared with TD-OCT. Disruption of the foveal pit as
      detected using SD-OCT is associated with reduced visual acuity.

PMID- 19855285
TI  - Incidence and risk factors of thrombocytopenia in patients receiving intermittent
      antiretroviral therapy: a substudy of the ANRS 106-window trial.
AB  - BACKGROUND: Incidence and risk factors for thrombocytopenia in patients
      discontinuing highly active antiretroviral therapy (HAART) have not been fully
      investigated. METHODS: Well-suppressed patients on HAART were randomized to
      continuous (CT) or intermittent therapy (IT) for 96 weeks. Incidence of
      thrombocytopenia (<150 x 10(3) platelets/mm(3)) was assessed and multivariate
      analysis performed to identify baseline predictors. Correlations were assessed
      between platelet, CD4, CD8 T-cell counts, and viral load after treatment
      interruption. RESULTS: Three hundred ninety-one patients were included, with a
      median baseline platelet count of 243,000/mm(3). The incidence of
      thrombocytopenia at week 96 was significantly higher in the IT versus the CT arm
      (25.4% versus 9.8%, respectively, P < 0.001) and median time to thrombocytopenia
      was 9 weeks. In multivariate analysis, the IT strategy: odds ratio (OR) = 4.1
      (2.1-7.9; P < 0.0001), a history of thrombocytopenia: OR = 11.9 (2.4-57.9; P =
      0.002), and a low baseline platelet count: OR = 3.4 (2.3-5.1; P < 0.0001) were
      associated with an increased risk of thrombocytopenia. Also, after treatment
      interruption, changes from baseline in platelet counts were correlated with
      changes in CD4 T-cell counts and plasma HIV RNA levels (P < 0.001 for both).
      CONCLUSIONS: Intermittent therapy is associated with a high incidence of
      thrombocytopenia, especially among patients with low platelet counts and a
      history of thrombocytopenia.

PMID- 19855290
TI  - Systemic high-sensitivity C-reactive protein level in pseudoexfoliation syndrome
      and pseudoexfoliation glaucoma.
AB  - PURPOSE: To evaluate the systemic high sensitivity C-reactive protein (hsCRP)
      levels in patients with pseudoexfoliation syndrome (XFS) and pseudoexfoliation
      glaucoma (XFG). MATERIALS AND METHODS: We prospectively examined 31 patients with
      XFS, 26 with XFG, and 25 controls. To the study patients with the exclusion of
      serious hypertension that do not have any cardiovascular and cerebrovascular
      disease and that diagnosed as XFS and XFG have been included. Each patient passed
      through a detailed blood sampling including hsCRP, biochemistry, and lipid
      profile. Plasma C-reactive protein (CRP) levels were measured with nephelometric
      method by using Beckman IMMAGE hsCRP reagent. RESULTS: Each group had similar
      demographic parameters including age, sex, body mass index, heart rate, and blood
      pressure. When we compared with controls, there was no statistically significant
      difference in the hsCRP and biochemistry results between the 3 groups. When all
      patients with pseudoexfoliation (PEX) compared with controls there was no
      difference. CONCLUSIONS: Our findings indicated no difference in the hsCRP level
      between XFS, XFG, and controls. This study suggests that CRP is not a predictive
      marker of inflammation and peripheral endothelial dysfunction in XFS, which is
      accepted as a systemic disorder.

PMID- 19855291
TI  - Retinal nerve fiber layer thickness measurement by Fourier-domain optical
      coherence tomography: a comparison between cirrus-HD OCT and RTVue in healthy
      eyes.
AB  - PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness measurements by 2
      Fourier-domain optical coherence tomography (OCT) instruments: Cirrus-HD OCT and
      RTVue. MATERIALS AND METHODS: Twenty-three eyes of 23 healthy participants
      underwent RNFL thickness measurement using both devices on the same day. The NMH4
      and Optic Disk Cube 200x200 protocols were used, respectively, for scan
      acquisition with RTVue and Cirrus-HD OCT. Measurements were compared by means of
      a paired t test. RESULTS: RTVue gave higher mean RNFL thickness values than
      Cirrus-HD OCT in the superior (128.44+/-22.48 vs. 119.73+/-18.22 mu, P=0.0002),
      inferior (137.15+/-21.99 vs. 124.94+/-22.51 mu, P<0.0001), nasal (77.58+/-15.61
      vs. 70.21+/-11.53 mu, P=0.0009), and temporal (78.09+/-10.05 vs. 67.08+/-9.60 mu,
      P<0.0001) quadrants, as well as a higher 360 degrees average measurement
      (105.88+/-14.59 vs. 95.21+/-12.45 mu, P<0.0001). The average difference between
      the 2 instruments showed a standard deviation too high to calculate a reliable
      correcting factor for comparing a pair of individual scans taken with the 2
      instruments (superior quadrant 8.70+/-9.19 mu; inferior quadrant 13.11+/-5.4 mu;
      nasal quadrant 7.37+/-9.18 mu; temporal quadrant 11.01+/-8.50 mu; average
      measurement: 10.67+/-4.88 mu). CONCLUSIONS: In healthy eyes RNFL measurements
      taken with RTVue and Cirrus-HD OCT show significant differences that make the
      measurements themselves noninterchangeable.

PMID- 19855292
TI  - Comparison of repeatability of retinal nerve fiber layer thickness measurement
      made using the RTVue Fourier-domain optical coherence tomograph and the GDx
      scanning laser polarimeter with variable or enhanced corneal compensation.
AB  - PURPOSE: To compare repeatability of measurements of peripapillary retinal nerve
      fiber layer thickness (RNFLT) made using the RTVue-100 Fourier-domain optical
      coherence tomograph against repeatability of those made using scanning laser
      polarimetry with variable corneal compensation or enhanced corneal compensation
      (GDx-VCC and GDx-ECC, respectively). METHODS: One eye of each of 37 participants
      (14 normal and ocular hypertensive subjects, 11 patients with moderate, and 12
      with severe glaucoma; groups 1, 2, and 3, respectively) was imaged using the
      RTVue Optic Nerve Head Map scan, GDx-VCC, and GDx-ECC, each 5 times on the same
      day. The coefficient of variation (CV) were compared. The P values <1% were
      considered as significant. RESULTS: For average RNFLT CV was significantly lower
      with RTVue (2.11%) than with GDx-ECC (3.22%, P=0.004), for all participants. For
      temporal quadrant RNFLT in all participants, and group 1, CV with RTVue (4.88%
      and 3.30%) was significantly lower than with GDx-ECC (7.40% and 5.88%; P=0.004),
      and tended to be lower than with GDx-VCC (6.81% and 5.80%; P=0.011 and 0.016,
      respectively). For all participants, CV for inferior quadrant RNFLT was
      significantly lower with RTVue (3.49%) than with GDx-VCC (5.20%, P=0.002). No
      other difference was seen for any other parameter in any subject group.
      CONCLUSIONS: Repeatability characterized by CV of RNFLT measurement with the
      RTVue Optic Nerve Head Map scan and GDx-VCC/GDx-ECC was similar, and sufficient
      for clinical purposes, both in normal subjects and in glaucoma patients with
      different disease severity. For average peripapillary RNFLT and temporal quadrant
      RNFLT, repeatability of RTVue was better than that of GDx-ECC, and tended to be
      better than that of GDx-VCC.

PMID- 19855289
TI  - The safety and efficacy of bimatoprost/timolol fixed combination: a 1-year double
      masked, randomized parallel comparison to its individual components in patients
      with glaucoma or ocular hypertension.

PMID- 19855293
TI  - Mild learning effect of short-wavelength automated perimetry using SITA program.
AB  - PURPOSE: To evaluate the learning effect at Short-wavelength Automated Perimetry
      (SWAP) using the Swedish Interactive Threshold Algorithm (SITA) program over the
      central 24 degrees on patients with ocular hypertension experienced with standard
      automated perimetry. METHODS: Twenty-seven patients underwent 5 SITA SWAP tests
      at intervals of 5+/-2 days in a randomized eye. Learning effect was defined as an
      improvement in results for duration, perimetric indices, foveal sensitivity,
      Glaucoma Hemifield Test, number of points with a P<5% and <1% in the total, and
      pattern deviation maps, total, central, paracentral, peripheral, and quadrant
      sensitivity. RESULTS: Learning effect was shown for foveal sensitivity (P=0.006,
      analysis of variance), which was significantly different only between the first
      (23.0 dB+/-4.1 dB) and the last test (24.7 dB+/-3.8 dB, P=0.003, t test) and was
      not affected by any demographic or ophthalmic characteristics of the population.
      All the other parameters did not show any significant learning effect.
      CONCLUSIONS: SITA SWAP is affected by a small learning effect interfering only
      with the first test, as opposite to full-threshold SWAP program, which previously
      showed severe learning artefacts. This fact may induce reconsideration of the
      clinical utilization of SWAP for the early diagnosis of glaucoma.

PMID- 19855294
TI  - Iris vascular tuft causing recurrent hyphema and raised IOP: a new indication for
      laser photocoagulation, angiographic follow-up, and review of laser outcomes.
AB  - We report the first case of iris vascular tuft (Cobb's tuft) causing recurrent
      spontaneous hyphema and raised intraocular pressure that underwent laser
      photocoagulation (LaP). For the first time, we report fluorescein angiogram
      guided LaP of the lesion and feeder vessels and 1 year angiographic follow up. We
      also review indications and outcomes of LaP of iris vascular tufts in the
      literature.

PMID- 19855296
TI  - Ophthalmic Surgical Procedures.

PMID- 19855295
TI  - Nocardia farcinica Infection of a Baerveldt implant and endophthalmitis in a
      patient with a Boston type I keratoprosthesis.
AB  - Eyes with implanted hardware carry a higher risk of infection. Here we report a
      rare case of Nocardia farcinica endophthalmitis and Baerveldt implant infection
      originating from infectious keratitis in a patient with a Boston type I
      keratoprosthesis. The infection resolved with aggressive surgical and medical
      treatment.

PMID- 19855297
TI  - Do optic discs get "thinner" or "narrower?".
AB  - PURPOSE: To survey the literature to determine how the dimensions of the
      neuroretinal rim are commonly described, and to clarify and standardize the
      description of changes in the dimensions of the neuroretinal rim in glaucoma.
      MATERIALS AND METHODS: Literature review of 275 articles describing the
      neuroretinal rim in glaucoma and a survey of ophthalmologists describing 2 disc
      photographs. Frequencies of descriptors of the neuroretinal rim were surveyed,
      which included "thinning" and "narrowing." RESULTS: Of the 275 articles, 80
      described the neuroretinal rim clinically. Forty-one articles used "thinning" to
      describe progressive loss of rim tissue in a radial axis, 13 articles used
      "narrowing" and rest used "width" to describe the characteristics of neuroretinal
      rim. Of the 295 ophthalmologists, 264 used "thinner," whereas 31 used "narrower"
      to describe the neuroretinal rim. CONCLUSIONS: Accurate phenotyping is an
      essential part of patient care, research, and training. "Thinning" is currently
      used more commonly than "narrowing" in the literature to describe progressive
      loss of the neuroretinal rim in a radial axis. It would be appropriate to use
      "narrowing" for radial loss or decrease in width and "thinning" for decrease in
      the thickness of the rim.

PMID- 19855298
TI  - Clinical characteristics and prognostic significance of disc hemorrhage in open
      angle and angle-closure glaucoma.
AB  - PURPOSE: To analyze the clinical characteristics and prognostic significance of
      disc hemorrhage in primary open-angle glaucoma (POAG), normal tension glaucoma
      (NTG), and primary angle-closure glaucoma (PACG). METHODS: Records of patients
      with POAG, NTG, or PACG and a history of disc hemorrhage were collected for this
      retrospective, observational cohort study. RESULTS: Of 1134 patients with POAG,
      513 with NTG and 770 with PACG, 63 (5.6%), 36 (7.0%), and 44 (5.7%),
      respectively, had disc hemorrhage over a mean of 9 years of follow-up. There were
      no significant differences in the laterality, episodes, duration of hemorrhage,
      and frequency of recurrent hemorrhage among the 3 types. The intraocular pressure
      and cup-to-disc ratio did not differ significantly between eyes with and fellow
      eyes without hemorrhage. There was a significant association between disc
      hemorrhage and visual field progression [odds ratio: 2.78 (P = 0.004), 3.75 (P =
      0.040), and 4.50 (P = 0.011) for POAG, NTG, and PACG, respectively]. CONCLUSIONS:
      Normal tension glaucoma has the highest incidence of disc hemorrhage, followed by
      PACG and POAG, which have similar incidence. The clinical characteristics of
      hemorrhage are not different among 3 types of glaucoma. The presence of disc
      hemorrhage is associated with the progression of glaucomatous optic neuropathy
      and visual field defects in POAG, NTG, and PACG.

PMID- 19855300
TI  - Corneal viscoelasticity differences between diabetic and nondiabetic glaucomatous
      patients.
AB  - PURPOSE: To investigate corneal viscoelasticity in primary open-angle glaucoma
      patients with and without diabetes mellitus, and to correlate corneal hysteresis
      (CH) with central corneal thickness (CCT). METHODS: In this cross-sectional
      study, 44 primary open-angle glaucoma patients [19 with diabetes (34 eyes) and 25
      without diabetes (40 eyes)] underwent a complete ophthalmic examination. Data
      collected by masked investigators included CH and CCT using the Ocular Response
      Analyzer. The mean of 3 measurements was considered for each test. We analyzed
      the difference between the mean CH in both groups using a general linear model.
      Partial correlation coefficient between CH and CCT was also calculated. RESULTS:
      Mean+/-SD age in diabetic and nondiabetic groups was 67.1+/-8.7 and 65.9+/-15.1,
      respectively (P=0.77). There was no significant difference regarding mean CCT
      between diabetic (531.7+/-31.3 mum) and nondiabetic (546.6+/-37.3 mum) groups
      (P=0.21). Patients with diabetes presented significantly higher CH values than
      patients without diabetes (9.1+/-1.9 mm Hg vs. 7.8+/-1.7 mm Hg, P=0.04). There
      was a significant and positive correlation between CH and CCT for all patients
      (r=0.407, P<0.001). CONCLUSIONS: Primary open-angle glaucoma patients with
      diabetes have significantly higher CH values than those without diabetes. CH and
      CCT results were positively correlated. These findings merit further
      investigation to assess the role of different CH values on glaucoma evaluation
      and susceptibility.

PMID- 19855299
TI  - Optic nerve head (ONH) topographic analysis by stratus OCT in normal subjects:
      correlation to disc size, age, and ethnicity.
AB  - PURPOSE: To study optic nerve head (ONH) topography parameters measured by
      Stratus optical coherence tomography (OCT) in normal subjects and to analyze ONH
      data for differences in relation to disc size, ethnicity, and age. METHODS: Three
      hundred sixty-seven normal subjects underwent Stratus optical coherence
      tomography ONH measurement using the fast optic disc scan protocol software
      package 3.0. Only ONH scans meeting specific qualification criteria were included
      for data analysis ensuring appropriate scan quality and reliability. ONH
      topographic parameters of qualified scans were analyzed for differences in
      regards to optic disc size, age, and ethnicity. RESULTS: Two hundred and twelve
      qualified ONH scans were included for data analysis. Mean disc area was 2.27+/
      0.41 mm and optic cup area, rim area, and horizontal integrated rim width
      increased with disc size, whereas vertical integrated rim area did not. Vertical
      integrated rim area, horizontal integrated rim width, and rim area decreased and
      cup area increased with age. Mean optic disc area was larger in African-Americans
      as compared with Hispanics or Whites and this difference was statistically
      significant. CONCLUSIONS: Optic cup area, rim area, and horizontal integrated rim
      width correlated to disc size. Vertical integrated rim area, horizontal
      integrated rim width, rim area, and cup area, changed with age. African-American
      optic discs had larger disc area measurements as compared with Whites optic discs
      and this difference was statistically significant.

PMID- 19855301
TI  - Assessing the Importance of IOP Variables in Glaucoma Using a Modified Delphi
      Process.
AB  - PURPOSE: To assess the degree of consensus among glaucoma experts on the
      measurement, characterization, and potential implications of intraocular pressure
      (IOP) and its fluctuation for glaucoma treatment. METHODS: A multinational panel
      of 9 glaucoma experts used a modified Delphi process to rate the level of
      agreement with 72 statements characterizing methods of measuring IOP, the
      importance of IOP reduction, and clinical implications of changes in IOP over
      time. After receiving a literature review, panelists rated each statement on a 9
      point Likert scale. A panel meeting was held to discuss the ratings followed by a
      second round of independent ratings. Consensus and nonconsensus regarding the
      panel's agreement with each statement were determined using a binomially
      distributed statistical definition. RESULTS: The panel found consensus in 46% of
      81 statements, nonconsensus in 6%, and indeterminate status in 48%. Categories
      having the highest proportion of statements with consensus were importance of IOP
      reduction (4/4 statements), importance of long-term IOP fluctuation and reduction
      (6/9), and impact of medication on short-term and long-term IOP fluctuation (6/10
      for each). Indeterminate statements were distributed unevenly with 74% of
      statements related to IOP measurement rated indeterminate compared with 38%
      related to the clinical implications of short-term and long-term IOP fluctuation.
      CONCLUSIONS: A modified Delphi process was useful in identifying areas of
      consensus regarding IOP measurement and importance of IOP fluctuation among
      glaucoma experts. Concurrently, the need for additional investigations assessing
      the role of IOP changes in glaucoma management is highlighted by the
      indeterminate and nonconsensus ratings.

PMID- 19855302
TI  - A comparison of clinical trial enrollment between adolescent and young adult
      (AYA) oncology patients treated at affiliated adult and pediatric oncology
      centers.
AB  - PURPOSE: Over the past 30 years, there has been a dramatic increase in the
      survival rates of younger pediatric cancer patients in contrast to adolescent and
      young adult (AYA) oncology patients. The reasons for this discrepancy are
      multifactorial, but it is clear that clinical trial enrollment correlates with
      better outcomes. PATIENTS AND METHODS: We examined the rate of clinical trial
      accrual of AYA oncology patients (aged 15 to 22 y) treated at affiliated
      pediatric and adult cancer centers, the Children's Hospital of Pittsburgh and the
      University of Pittsburgh Cancer Institute. We retrospectively analyzed all new
      cancer diagnoses and clinical trial enrollment status between 2003 and 2006 for
      AYA patients at both institutions. RESULTS: There were 91 new AYA cancer
      diagnoses at Children's Hospital of Pittsburgh, of which 24 (26%) were enrolled
      on a clinical trial. During the same time period, only 5 of 121 new AYA cancer
      patients (4%) at University of Pittsburgh Cancer Institute were enrolled on a
      clinical trial, which was significantly lower (P<0.001). CONCLUSIONS: Our data
      demonstrate that clinical trial enrollment was superior when AYA patients were
      treated at a pediatric cancer center. As most AYA patients are not treated at
      pediatric centers, this may partly explain why their cure rates have not improved
      as significantly as younger pediatric oncology patients.

PMID- 19855303
TI  - Prospective monitoring for invasive aspergillosis using galactomannan and
      polymerase chain reaction in high risk pediatric patients.
AB  - BACKGROUND: The diagnosis of invasive aspergillus remains a challenge in the care
      of high-risk patients. Outcomes are improved when invasive aspergillus is
      diagnosed early, prompting the initiation of appropriate antifungal therapy. We
      evaluated the utility of prospective monitoring for invasive aspergillosis (IA)
      using biomarkers such as serum galactomannan (GM) and/or blood polymerase chain
      reaction (PCR) in high-risk pediatric patients. METHODS: Patients with high-risk
      leukemia (HRL) or allogenic hematopoietic cell transplant (HCT) recipients were
      prospectively monitored twice weekly for IA using GM and PCR for Aspergillus
      species. RESULTS: Sixty-eight patients had collected >or=2 specimens. The 1086
      specimens were collected; 627 from HRL (58%) and 459 (42%) from HCT recipients.
      Median specimens/patient was 11.0 (2 to 58), and median follow-up/patient was
      98.5 days (14 to 437). Fifty-six percent of samples were obtained from patients
      receiving mold-active agents; 32% HRL and 89% HCT. There were no proven, 3
      probable, and 20 possible episodes of IA. Thirteen specimens (1.2%) from 4
      patients (5%) were GM+. None were positive by PCR. CONCLUSIONS: The prospective
      use of GM and PCR in this high-risk pediatric population did not identify cases
      of proven IA. A high false positive rate was not detected. It is speculated that
      changes in clinical practice, such as early use of empiric and/or prophylactic
      mold-active agent and frequent imaging studies have impacted the epidemiology of
      IA. In a population with low incidence of IA, the use of these assays as a
      screening device on blood may not further enhance current outcomes.

PMID- 19855304
TI  - Zygomycetes infections in pediatric hematology oncology patients: a case series
      and review of the literature.
AB  - Fungi from the Zygomycetes class are increasingly recognized causes of infection
      in immunosuppressed children, but no comprehensive literature review and few case
      series have been published on the topic. A case series of 6 pediatric oncology
      patients with Zygomycetes infections cared for at our institution was
      constructed, and a concurrent search of the English language literature for
      Zygomycetes infections in children with oncologic disorders was undertaken. Our
      case series described 6 patients (5 male) between the ages of 2.5 and 19.5 years.
      One patient was diagnosed with rhinocerebral disease, 2 with rhinosinusitis, 2
      with pulmonary involvement, and 1 with a gastrointestinal presentation. Five
      patients survived. Our literature review identified 82 cases from 61 studies. The
      mean subject age was 10.8 years (1.4 to 21.0 y). About 92.7% of all patients
      suffered from some form of leukemia, with 70.7% suffering from acute
      lymphoblastic leukemia. Overall, 58.5% of reported patients survived, with
      individuals with disseminated disease showing the worst prognosis (68.2%
      mortality) and those with cutaneous disease the best (14.3% mortality). Survival
      is increasingly reported in the literature, perhaps as a result of improved
      diagnostic capabilities, increased physician awareness and increased reliance on
      adjunctive surgical therapy.

PMID- 19855305
TI  - Sinonasal mucormycosis in immunocompromised pediatric patients.
AB  - OBJECTIVE: Sinonasal mucormycosis is a rare fulminant disorder that typically
      affects immunocompromised patients. This article focuses primarily on the
      clinical manifestations and the importance of early diagnosis and treatment of
      this disease. PATIENTS AND METHODS: Four pediatric cases of sinonasal
      mucormycosis encountered over an 8-year-period in our institution are reported.
      The initial presenting symptoms, physical examination, computed tomography,
      intraoperative, and histopathologic findings are described. The underlying
      immunosuppressive diseases are also outlined. RESULTS: The most common signs and
      symptoms were fever, rhinorrhea, facial erythema and edema, and very pale nasal
      mucosa. Despite these manifestations, the diagnosis of sinonasal mucormycosis was
      delayed, except in one child. Computed tomography scan findings were nonspecific
      and did not correlate well with surgical and pathologic findings. Treatment
      consisted in a combination of antifungal agents, multiple aggressive surgical
      debridements, and control of the underlying disease. In the postoperative course,
      1 child died of the disease, 1 developed a persistent unilateral blindness, 1 was
      lost to follow-up, and the last 1 was cured with no sequelae. CONCLUSIONS:
      Sinonasal mucormycosis in the immunocompromised pediatric population is an
      uncommon but potentially fatal disease. A high index of suspicion is of utmost
      importance to decrease its related morbidity and mortality.

PMID- 19855307
TI  - The impact of lower extremity mass and inertia manipulation on sprint kinematics.
AB  - Resistance sprint training is a sprint-specific training protocol commonly
      employed by athletes and coaches to enhance sprint performance. This research
      quantified the impact of lower extremity mass and inertia manipulation on key
      temporal and kinematic variables associated with sprint performance. A 3
      dimensional analysis of 40 m sprinting was conducted on 8 elite sprinters under
      normal conditions and resisted sprint training. Results of the study showed that
      lower extremity additional mass training (at 10% individual segment weight) led
      to a significant reduction in sprint time for both the 10-m to 20-m and the 30-m
      to 40-m splits and the total 40 m measure. The stride velocity throughout the 20
      m to 30-m phase of the sprint trials was also shown to be significantly reduced
      in the lower extremity mass and inertia manipulation condition. Importantly, no
      significant differences were observed across the remaining spatiotemporal
      variables of stride length, stride frequency, total stride time, and ground
      contact time. For coaches and athletes, the addition of specific lower extremity
      mass could improve the athlete's sprint performance without any measured effect
      on the technique of highly trained elite sprinters.

PMID- 19855306
TI  - Characterization of S-glutathionyl hemoglobin in homozygous sickle cell disease.
AB  - S-glutathionyl hemoglobin is a proposed biomarker of oxidative stress but has not
      been measured in sickle cell disease patients. Unlike the S-glutathionyl adduct
      of normal adult hemoglobin, S-glutathionyl sickle hemoglobin (HbSSG) cannot be
      directly measured by capillary isoelectric focusing, because it coelutes with
      fetal hemoglobin (HbF). This suggests that HbF, measured in sickle cell patients
      with or without hydroxyurea therapy, might contain endogenous HbSSG. As S
      glutathionyl hemoglobin can form during sample storage, HbSSG could falsely
      elevate HbF levels in stored samples. We measured HbSSG based on the quantitative
      difference in the heterogeneous HbF/HbSSG peak before and after hemolysates were
      treated with dithiothreitol. Paired t tests showed that dithiothreitol reduced
      HbF/HbSSG in blood from pediatric sickle cell patients (n=25, mean decrease+/
      SD=1.0%+/-0.6, P<0.05) but not in normal infants (n=25). Higher HbF levels in
      hydroxyurea-treated patients (n=5) were not attributable to HbSSG. HbSSG
      increased significantly within 1 day in samples stored at -20 degrees C but was
      unchanged in samples stored 60 days at-70 degrees C. We conclude that blood from
      sickle cell patients contained up to 2.2% HbSSG, and that endogenous HbSSG is a
      minor interferent in the measurement of HbF in fresh blood but a major
      interferent in improperly stored samples.

PMID- 19855308
TI  - A comparison of free weight squat to Smith machine squat using electromyography.
AB  - The purpose of this experiment was to determine whether free weight or Smith
      machine squats were optimal for activating the prime movers of the legs and the
      stabilizers of the legs and the trunk. Six healthy participants performed 1 set
      of 8 repetitions (using a weight they could lift 8 times, i.e., 8RM, or 8
      repetition maximum) for each of the free weight squat and Smith machine squat in
      a randomized order with a minimum of 3 days between sessions, while
      electromyographic (EMG) activity of the tibialis anterior, gastrocnemius, vastus
      medialis, vastus lateralis, biceps femoris, lumbar erector spinae, and rectus
      abdominus were simultaneously measured. Electromyographic activity was
      significantly higher by 34, 26, and 49 in the gastrocnemius, biceps femoris, and
      vastus medialis, respectively, during the free weight squat compared to the Smith
      machine squat (p < 0.05). There were no significant differences between free
      weight and Smith machine squat for any of the other muscles; however, the EMG
      averaged over all muscles during the free weight squat was 43% higher when
      compared to the Smith machine squat (p < 0.05). The free weight squat may be more
      beneficial than the Smith machine squat for individuals who are looking to
      strengthen plantar flexors, knee flexors, and knee extensors.

PMID- 19855309
TI  - Effects of different strength training methods on postexercise energetic
      expenditure.
AB  - Although many studies have demonstrated the efficacy of strength training in
      increasing energetic expenditure (EE) both during and after training sessions,
      there are no studies available that analyze the influence on EE of the order in
      which exercises are performed. Accordingly, the objective of this study was to
      verify whether the order in which exercises are performed, represented by 2
      different methods of strength training (circuit [CT] and pre-exhaustion [PE]),
      influences the magnitude of the excess postexercise oxygen consumption (EPOC) as
      well as the EE. Eight nonstrength-trained women participated in the study. Two
      strength training sessions, with different orders of execution, were held with 7
      exercises performed with loads of between 50% and 55% of 1 repetition maximum
      (1RM). The oxygen uptake was measured before the training sessions, and the
      difference between the values found was taken as the EPOC of each training
      session and used in later analysis. No significant differences were found in
      either the EPOC (CT: 7.19 L +/- 6.17 an. PE: 7.22 +/- 5.84 L) or the postexercise
      EE (CT: 34.67 +/- 29.76 Kcal, PE: 34.77 +/- 28.15 Kcal) of the 2 training
      methodologies. Our results indicate that, in strength training, the magnitude of
      the EPOC is not linked to the order in which the exercises are performed.
      However, the absence of recovery periods between the sets and the exercises
      promotes an increase in the magnitude of the EPOC to the levels found in training
      sessions with higher percentages of 1RM.

PMID- 19855310
TI  - Effect of warm-ups involving static or dynamic stretching on agility, sprinting,
      and jumping performance in trained individuals.
AB  - The objective of the present study was to investigate the effects of static and
      dynamic stretching alone and in combination on subsequent agility, sprinting, and
      jump performance. Eight different stretching protocols: (a) static stretch (SS)
      to point of discomfort (POD); (b) SS less than POD (SS<POD); (c) dynamic
      stretching (DS); (d) SS POD combined with DS (SS POD + DS); (v) SS<POD combined
      with DS (SS<POD + DS); (vi) DS combined with SS POD (DS + SS POD); (vii) DS
      combined with SS<POD (DS + SS<POD); and (viii) a control warm-up condition
      without stretching were implemented with a prior aerobic warm-up and followed by
      dynamic activities. Dependent variables included a 30-m sprint, agility run, and
      jump tests. The control condition (4.2 +/- 0.15 seconds) showed significant
      differences (p = 0.05) for faster times than the DS + SS<POD (4.28s +/- 0.17)
      condition in the 30-m (1.9%) sprint. There were no other significant differences.
      The lack of stretch-induced impairments may be attributed to the trained state of
      the participants or the amount of time used after stretching before the
      performance. Participants were either professional or national level elite
      athletes who trained 6-8 times a week with each session lasting approximately 90
      minutes. Based on these findings and the literature, trained individuals who wish
      to implement static stretching should include an adequate warm-up and dynamic
      sport-specific activities with at least 5 or more minutes of recovery before
      their sport activity.

PMID- 19855311
TI  - Maximal strength training improves cycling economy in competitive cyclists.
AB  - The purpose of the present study was to investigate the effect of maximal
      strength training on cycling economy (CE) at 70% of maximal oxygen consumption
      (Vo2max), work efficiency in cycling at 70% Vo2max, and time to exhaustion at
      maximal aerobic power. Responses in 1 repetition maximum (1RM) and rate of force
      development (RFD) in half-squats, Vo2max, CE, work efficiency, and time to
      exhaustion at maximal aerobic power were examined. Sixteen competitive road
      cyclists (12 men and 4 women) were randomly assigned into either an intervention
      or a control group. Thirteen (10 men and 3 women) cyclists completed the study.
      The intervention group (7 men and 1 woman) performed half-squats, 4 sets of 4
      repetitions maximum, 3 times per week for 8 weeks, as a supplement to their
      normal endurance training. The control group continued their normal endurance
      training during the same period. The intervention manifested significant (p <
      0.05) improvements in 1RM (14.2%), RFD (16.7%), CE (4.8%), work efficiency
      (4.7%), and time to exhaustion at pre-intervention maximal aerobic power (17.2%).
      No changes were found in Vo2max or body weight. The control group exhibited an
      improvement in work efficiency (1.4%), but this improvement was significantly (p
      < 0.05) smaller than that in the intervention group. No changes from pre- to
      postvalues in any of the other parameters were apparent in the control group. In
      conclusion, maximal strength training for 8 weeks improved CE and efficiency and
      increased time to exhaustion at maximal aerobic power among competitive road
      cyclists, without change in maximal oxygen uptake, cadence, or body weight. Based
      on the results from the present study, we advise cyclists to include maximal
      strength training in their training programs.

PMID- 19855312
TI  - Development and validation of a comprehensive new hepatobiliary software. Part
      II: Segmental liver function.
AB  - OBJECTIVE: This study was undertaken to develop comprehensive new hepatobiliary
      software to quantify segmental and lobar liver function and to obtain FDA
      approval. METHODS: Hepatobiliary software written on JAVA platform and loaded on
      to a PC accepts 99mTc-HIDA dicom image data transferred from a gamma camera.
      Liver boundary was determined by threshold-based auto edge detection and liver
      height at right midclavicular (RMCL) line. Geometric mean area of the physiologic
      right lobe, physiologic left lobe and total liver area were measured. Segmental
      liver function was determined using the 5th minute frame as the default (100%).
      RESULTS: In 24 control participants, mean (+/-SD) liver height at RMCL was 14.7+/
      0.12 cm. Geometric mean area of the physiologic right lobe was 116+/-3 cm2, left
      lobe 96+/-4 cm2, and total liver area 212+/-3 cm. Right upper lobe (segments 7
      and 8) contributed 31+/-0.7%, right lower lobe (segments 5 and 6) 34+/-0.6%, left
      medial (segments 4A and 4B) 24+/-1%, left lateral (segments 2 and 3) 10+/-2%, and
      caudate lobe (segment 1) 1+/-0.02% of total liver function. In 23 patients,
      contrast three-dimensional computerized tomographic volume of the right lobe was
      1194+/-419 ml, left lobe 434+/-221 ml, and total liver volume 1628+/-490 ml.
      Right lobe area was 120+/-30 cm2, left lobe (plus caudate) 88+/-29 cm2 with total
      liver area of 208+/-51 cm. Right upper lobe (segments 7 and 8) contributed 33+/
      10%, right lower lobe (segments 5 and 6) 34+/-7%, left medial (segments 4A and
      4B) 23+/-6%, left lateral (segments 2 and 3) 9+/-3%, and caudate lobe (segment 1)
      1+/-0.4% of total liver function. There was good correlation of RMCL height, and
      area of right lobe and total liver with computerized tomographic liver volume.
      Correlation of percentage volume with percentage function was excellent.
      CONCLUSION: New FDA approved software provides quantitative assessment of
      segmental, lobar, and total liver size and function from a planar 99mTc-HIDA
      cholescintigraphy and may enable universal standardization in nuclear hepatology.
      Quantification may aid surgeons in the determination of the amount of tissue
      resection during liver surgery.

PMID- 19855313
TI  - Neonatal hair analysis by liquid chromatography-high-resolution mass spectrometry
      to reveal gestational exposure to venlafaxine.
AB  - Venlafaxine (VEN) is a second generation antidepressant drug, belonging to the
      class of selective serotonine and norepinephrine reuptake inhibitors, widely used
      in the treatment of depression and anxiety disorders. Though its pharmacological
      profile is considered safe, treatment with VEN can cause several nervous,
      gastrointestinal, cardiovascular and genitourinary adverse effects. Therapeutic
      drug monitoring for VEN could be useful in specific situations, including
      exposure to the drug during pregnancy. A liquid chromatography-high-resolution
      mass spectrometry method was developed and validated for the assay of VEN in 2.5
      mg hair samples from 2 newborn identical twin sisters. The analyte was extracted
      by a rapid, simultaneous pulverization and extraction step, allowing analysis
      when tiny amounts of hair are available, such as in the case of a newborn.
      Gradient elution on an Atlantis T3 column was performed using nordiazepam-d5 as
      an internal standard. Positive ion electrospray ionization and high-resolution
      full scan determination were performed in an Orbitrap mass spectrometer. The
      method was linear range in the range 0.2-25 ng/mg, and had a quantification limit
      of 0.2 ng/mg, a relative standard deviation in the range 0.7%-1.4% (intra-assay)
      and 2.9%-5.9% (interassay), and was accurate (as % relative error) in the range 
      9% to + 2%, using a hair sample size as low as 2.5 mg. The utilization of high
      resolution/high accuracy mass spectrometry in full-scan mode allowed both the
      quantitative determination of VEN in the hair of the 2 newborns and the
      straightforward identification of 4 VEN metabolites, namely O
      desmethylvenlafaxine, N-desmethylvenlafaxine, N,N-didesmethylvenlafaxine, and N,O
      didesmethylvenlafaxine, by means of retrospective screening, thus unequivocally
      documenting in utero exposure.

PMID- 19855314
TI  - Time of drug administration, CYP3A5 and ABCB1 genotypes, and analytical method
      influence tacrolimus pharmacokinetics: a population pharmacokinetic study.
AB  - Tacrolimus (TAC) pharmacokinetics are characterized by a very high variability
      that complicates its therapeutic use. The aims of this study were: 1) to identify
      and model the effect of demographic, clinical, and genetic factors and time of
      drug administration on TAC pharmacokinetic variability; and 2) to assess the
      influence of the analytical method by modeling the TAC blood concentrations
      measured simultaneously by microparticle enzyme immune assay (MEIA) and liquid
      chromatography-tandem mass spectroscopy. Data from 19 renal transplant candidates
      were analyzed. A total of 266 blood samples were analyzed for TAC by both
      techniques. Linear regression and Bland and Altman analyses were performed to
      compare TAC blood concentrations obtained with MEIA and liquid chromatography
      tandem mass spectroscopy. A population pharmacokinetic analysis was performed. As
      expected, blood concentrations obtained by MEIA were higher than those obtained
      by liquid chromatography-tandem mass spectroscopy. A two-compartment model with
      first-order absorption and elimination best fit TAC blood concentrations. An
      exponential model was used to describe the interindividual and interoccasion
      variability and a mixed model was retained for the residual variability. A
      supplementary proportional term was necessary for the residual error in case of
      TAC blood concentrations determined by MEIA. The following covariates were
      retained in the final model: time of drug administration on the absorption rate
      constant and CYP3A5 and ABCB1 genotypes on the TAC apparent clearance. All
      parameter estimates had reliable values. The final model was found to be stable
      and generated parameters with good precision. The validation of the final model
      by bootstrapping (2000 bootstraps), case deletion diagnostics, crossvalidation,
      and visual predictive check (1000 simulated subjects) gave satisfactory results.
      This is the first population pharmacokinetic study confirming the
      chronopharmacokinetics of TAC and showing an effect of ABCB1 genotype and
      analytical method on TAC pharmacokinetics. These results may be helpful for TAC
      dose individualization.

PMID- 19855315
TI  - Effects of the P-glycoprotein inducer carbamazepine on fexofenadine
      pharmacokinetics.
AB  - The aim of this study was to evaluate the possible effects of carbamazepine, a P
      glycoprotein inducer, on fexofenadine pharmacokinetics. Twelve healthy Japanese
      volunteers (nine males and three females) were enrolled in this study after
      giving written informed consent. This randomized open-label study consisted of
      two phases (control and 7-day treatment) with a 2-week washout period. In the
      control phase, volunteers received 60 mg fexofenadine hydrochloride after an
      overnight fast. In the treatment phase, carbamazepine was dosed 100 mg three
      times daily (for a total daily dose of 300 mg) for 7 days, and on Day 7, a single
      60-mg dose of fexofenadine was coadministered with a 100-mg dose of
      carbamazepine. The plasma concentrations and urinary excretion of fexofenadine
      were measured for 24 hours after dosing. Carbamazepine pretreatment significantly
      altered fexofenadine pharmacokinetics, decreasing the mean (+/- standard
      deviation) peak plasma concentration from 176.6 (+/- 82.1) ng/mL to 103.2 (+/-
      33.6) ng/mL (P < 0.01) and the area under the plasma concentration-time curve
      from 1058.4 (+/- 528.7) ng/h/mL to 604.8 (+/- 255.9) ng/h/mL (P < 0.01) without
      changing the elimination half-life. Relatively, carbamazepine significantly
      reduced the amount of fexofenadine excreted into the urine from 8.1 (+/- 2.1) mg
      to 4.5 (+/- 1.4) mg (P < 0.001), although the renal clearance of fexofenadine
      remained constant between the two study phases. Thus, this study indicates that
      carbamazepine significantly decreases fexofenadine plasma concentrations,
      probably as a result of P-glycoprotein induction in the small intestine.
      Carbamazepine treatment, therefore, is of moderate clinical significance for
      patients receiving fexofenadine.

PMID- 19855316
TI  - Effects of different periodization models on rate of force development and power
      ability of the upper extremity.
AB  - The purpose of our study was to compare the effects of 2 different periodization
      models on strength and power variables under dynamic and static conditions in the
      bench press. Participants of the experimental groups were male sport students
      experienced in weight training (age: 23.98 +/- 3.14 yr). Subjects were tested for
      the 1 repetition maximum (1RM) in the bench press, maximal movement velocity
      (Vmax) in the bench press throw (16.9 kg), maximal voluntary contraction (MVC),
      and maximal rate of force development (MRFD) in 90 degrees elbow and shoulder
      angle in the isometric bench press. According to their 1RM, subjects were
      parallelized and assigned to 1 of either 2 training groups: strength-power
      periodization (SPP, n = 13) or daily undulating periodization (DUP, n = 14).
      Subjects trained for 14 weeks, 3 days per week. In the strength-power sessions,
      both groups were instructed to lift the weight as explosively as possible. In
      addition, a control group (n = 13) was used for comparison. One repetition
      maximum and Vmax improved significantly through training (p <or= 0.05), with no
      significant changes in MVC and MRFD. Experimental groups showed no significant
      group differences in any variable. The results indicate that, in short-term
      training using previously trained subjects, no differences in 1RM and power are
      seen between DUP and SPP. As used in our undulating regime, additional training
      in strength endurance could lead to exhaustion effects and furthermore does not
      provide an adequate training stimulus for power because of its low training
      intensity. In spite of this, according to the present findings, it has no
      negative effect on the application of a neural stimulus that is needed for a
      strength-power session if adequate regeneration time between workouts is
      guaranteed.

PMID- 19855317
TI  - Neuromuscular activity during bench press exercise performed with and without the
      preexhaustion method.
AB  - The purpose of the present study was to investigate the effects of exercise order
      on the tonic and phasic characteristics of upper-body muscle activity during
      bench press exercise in trained subjects. The preexhaustion method involves
      working a muscle or a muscle group combining a single-joint exercise immediately
      followed by a multi-joint exercise (e.g., flying exercise followed by bench press
      exercise). Twelve subjects performed 1 set of bench press exercises with and
      without the preexhaustion method following 2 protocols (P1-flying before bench
      press; P2-bench press). Both exercises were performed at a load of 10 repetition
      maximum (10RM). Electromyography (EMG) sampled at 1 kHz was recorded from the
      pectoralis major (PM), anterior deltoid (DA), and triceps brachii (TB). Kinematic
      data (60 Hz) were synchronized to define upward and downward phases of exercise.
      No significant (p > 0.05) changes were seen in tonic control of PM and DA muscles
      between P1 and P2. However, TB tonic aspect of neurophysiologic behavior of motor
      units was significantly higher (p < 0.05) during P1. Moreover, phasic control of
      PM, DA, and TB muscles were not affected (p > 0.05). The kinematic pattern of
      movement changed as a result of muscular weakness in P1. Angular velocity of the
      right shoulder performed during the upward phase of the bench press exercise was
      significantly slower (p < 0.05) during P1. Our results suggest that the
      strategies set by the central nervous system to provide the performance required
      by the exercise are held constant throughout the exercise, but the tonic aspects
      of the central drive are increased so as to adapt to the progressive occurrence
      of the neuromuscular fatigue. Changes in tonic control as a result of the
      muscular weakness and fatigue can cause changes in movement techniques. These
      changes may be related to limited ability to control mechanical loads and
      mechanical energy transmission to joints and passive structures.

PMID- 19855318
TI  - Effects of intermittent-endurance fitness on match performance in young male
      soccer players.
AB  - The purpose of this study was to examine the effect of specific endurance (Yo-Yo
      Intermittent recovery test level 1, Yo-Yo IR1) on match performance in male youth
      soccer. Twenty-one young, male soccer players (age 14.1 +/- 0.2 years) were
      involved in the study. Players were observed during international championship
      games of corresponding age categories and completed the Yo-Yo IR1 on a separate
      occasion. Physical (distance coverage) and physiological match demands were
      assessed using Global Positioning System technology and heart rate (HR) short
      range telemetry, respectively. During the match (two 30-minutes halves), players
      covered 6,204 +/- 731 m, of which 985 +/- 362 m (16%) were performed at high
      intensities (speed >13 kmxh, HIA). A significant decrement (3.8%, p = 0.003) in
      match coverage was evident during the second half. No significant (p = 0.07)
      difference between halves was observed for HIA (p = 0.56) and sprint (speed >18
      kmxh, SPR) distances. During the first and second halves, players attained the 86
      +/- 5.5 and 85 +/- 6.0% of HRmax (p = 0.17), respectively. Peak HR during the
      first and second halves were 100 +/- 4 and 99.4 +/- 4.7% of HRmax, respectively.
      Yo-Yo IR1 performance (842 +/- 352 m) was significantly related to match HIA (r =
      0.77, p < 0.001) and total distance (r = 0.65, p = 0.002). This study's results
      showed that specific endurance, as determined by Yo-Yo IR1 performance,
      positively affects physical match performance in male young soccer players.
      Consequently, the Yo-Yo IR1 test may be regarded as a valid test to assess game
      readiness and guide training prescription in male youth soccer players.

PMID- 19855319
TI  - The effects of postactivation potentiation on sprint and jump performance of male
      academy soccer players.
AB  - The purpose of this investigation was to evaluate the postactivation potentiation
      (PAP) effects of both dynamic and isometric maximum voluntary contractions (MVCs)
      on sprint and jump performance and establish whether PAP methods could be used
      effectively in warm up protocols for soccer players. Twelve male soccer players
      performed 4 warm up protocols in a cross-over, randomized, and counterbalanced
      design. In addition to a control warm up, subjects performed deadlift (5
      repetitions at 5 repetitions maximum), tuck jump (5 repetitions), and isometric
      MVC knee extensions (3 repetitions for 3 s) as PAP treatments in an otherwise
      identical warm up protocol. After each treatment, the subjects underwent 3 10 m
      and 20 m sprints 4, 5, and 6 minutes post-warm up and 3 vertical jumps (VJ) at 7,
      8, and 9 minutes post-warm up. Repeated measures analysis of variance showed no
      significant differences in the first 10 m (p = 0.258) and 20 m (p = 0.253) sprint
      and VJ (p = 0.703) performance and the average 10 m (p = 0.215), 20 m (p =
      0.388), and VJ (p = 0.529) performance between conditions. There were also no
      significant differences in performance responses between the strongest and
      weakest subjects, but large variations in individual responses were found between
      the subjects. The findings suggest that there was no significant group PAP effect
      on sprint and jump performance after dynamic and isometric MVCs compared with a
      control warm up protocol. However, the large variation in individual responses (
      7.1% to +8.2%) suggests PAP should be considered on an individual basis. Factors
      such as method, volume, load, recovery, and interindividual variability of PAP
      must be considered in the practical application of PAP and the rigorous research
      design of future studies to evaluate the potential for performance enhancement.

PMID- 19855320
TI  - Strength, power, speed, and agility of women basketball players according to
      playing position.
AB  - The aim of the present study was to investigate the effect of playing position on
      strength, power, speed, and agility performances of women basketball players.
      Thirty subjects playing at national level participated in this study. They were
      divided into 3 groups according to playing position: guards (positions 1 and 2),
      forwards (positions 3 and 4), and centers (position 5). Each subject performed 8
      tests presented in a random order: The 30-second Wingate Anaerobic test (WAnT),
      isokinetic testing of the knee extensors, 2 types of jump tests, a 20-m sprint,
      the agility T-test, a suicide run, and a basketball chest pass. Statistical
      differences between playing positions were assessed using a 1-way analysis of
      variance (ANOVA) and Scheffe post hoc analyses. Results showed that guards
      performed significantly better than centers for the relative peak and mean power
      achieved during the WAnT (+13% and +16.9%, respectively), relative peak torque of
      knee extensors (+19.5%), single-leg jump (+21.8), suicide run (+7.5%), and
      agility T-test (+6.4%, p < 0.05). In addition, guards achieved significantly
      better performances than forwards in the suicide run test (+7.1%) and forwards
      were characterized by a greater peak torque of the knee extensors compared to
      centers (+22.1%). These results indicate that specific fitness training must be
      undertaken according to playing position. The ability to perform the suicide run,
      the single-leg jump, and the different movements involved in the agility T-test
      must be developed in guards. In contrast, speed over short distances and strength
      development of lower body and upper body should be performed by all playing
      positions.

PMID- 19855321
TI  - Aerobic and explosive power performance of elite italian regional-level
      basketball players.
AB  - The aim of this study was to examine the aerobic fitness and lower-limbs
      explosive-power abilities of Italian regional-level amateur basketball players.
      Participants were basketball players playing successfully at a senior (S, n = 11)
      and junior (J, n = 11) regional level. Players maximal oxygen uptake (VO2max) was
      assessed with them wearing a portable gas analyzer (K4b, COSMED, Rome, Italy)
      during an exercise mode-specific multistage fitness test (yo-yo endurance test
      [Yo-Yo]). Knee extensors and plantar flexors explosive power was assessed with
      countermovement jump (CMJ) and stiff-leg jumps (SL), respectively. Jumps were
      performed using a switch mat connected to a computer (Muscle Lab, Bosco System,
      Rome, Italy). Jumps' fly (FT) and contact times (CT) were used for jump
      performances calculations. Stiff-Leg FT versus CT ratio (SL/CT) was considered as
      representative of lower-leg explosive power, whereas SL/CMJ.100 was considered as
      sign of the explosive-power balance between lower and upper leg muscles. Players'
      VO2max was 60.88 +/- 6.26 and 50.33 +/- 3.98 mLxkgxmin for J and S, respectively
      (p < 0.05). A significant difference was found in SL/CT between S and J players.
      Yo-Yo performance was not significantly different between groups (2,055 +/- 267
      and 2,020 +/- 174 m for S and J, respectively, p > 0.05). Lower-leg explosive
      power showed to be positively related to distance covered during Yo-Yo. Study
      results showed that 50 mLxkgxmin is a sufficient VO2max value for competing at a
      regional level. Calf explosive power should be considered to improve sport
      specific running performance in basketball using plyometrics and whole body
      lifts.

PMID- 19855322
TI  - The acute effects of heavy and light resistances on the flight time of a
      basketball push-pass during upper body complex training.
AB  - The aim of this study was to investigate the acute effect of high-load and low
      load complex training on upper-body performance-determined by the flight time of
      a basketball push-pass. Twelve competitive male athletes (21.8 +/- 4.5 years,
      82.0 +/- 11.7 kg, 181.6 +/- 5.6 cm), with at least 6 months weight training
      experience and no musculoskeletal disorders, undertook 3 testing conditions.
      Condition 1 involved 5 repetitions at 85% of a 1 repetition maximum (1RM) bench
      press; Condition 2 involved 5 repetitions of a 2.3-kg medicine ball push-pass;
      and Condition 3 was the control, where participants rested for the equivalent
      time of the other conditions ( approximately 20 seconds). Each condition was
      preceded and followed by an electronically timed basketball push-pass. Results
      indicate a significant (3.99%, P = 0.001) reduction in flight time following the
      completion of Condition 1 (85% 1RM) but no significant changes (1.96%, P = 0.154)
      were seen following Condition 2 (medicine ball push-pass). Furthermore, there was
      a significant difference (P = 0.016) between Condition 1 (85% 1RM) and Condition
      2 (medicine ball throw). This study appears to confirm previous research
      suggesting that high loads are required to elicit a potentiation effect. For
      those athletes wishing to produce a short-term enhancement of power, they should
      consider loads in the region of 85% 1RM. Results with the lower load showed
      greater variation, with some individuals responding and others not. Because there
      appears to be an individual potentiation response to lighter loads, we recommend
      that, when equipment is limited, athletes and coaches experiment with a range of
      loads when performing contrast training.

PMID- 19855323
TI  - The effect of different training programs on eccentric energy utilization in
      college-aged males.
AB  - The Eccentric Utilization Ratio (EUR), which is the ratio of countermovement jump
      (CMJ) to squat jump (SJ) performance measures, is a useful indicator of training
      status in elite athletes and their utilization of the stretch-shortening cycle.
      This investigation sought to determine if EUR was sensitive to different types of
      resistance training in untrained college-aged males. Twenty-nine college-aged
      males completed 8 weeks of training and were randomly allocated to 1 of 3
      training programs: weight training (n = 10), plyometrics (n = 10), or
      weightlifting (n = 9). Testing occurred 3 times (pre, mid, post) with a CMJ and
      SJ conducted on a force plate integrated with a position transducer. Height,
      weight, and a 1RM (repetition maximum) squat also were measured. Weightlifting
      significantly (p < 0.05) helped subjects jump higher and produce more power than
      plyometrics for height and power for both CMJ and SJ results. This investigation
      indicated EUR did not significantly change, suggesting that this type of
      performance indicator may not be useful in a recreationally active population.
      Alternatively, an 8-week training program might not be a long enough time period
      to see changes in this group of participants. Results did indicate that high
      velocity and high-force training programs, consisting of weightlifting and
      plyometrics, improved lower-body performance, especially in the areas of jump
      height and power.

PMID- 19855324
TI  - Hormonal responses to different resistance exercise schemes of similar total
      volume.
AB  - This study assessed the effect of different resistance exercise scheme (RES)
      designs of similar total of load lifted on the responses of testosterone,
      cortisol, and creatine kinase (CK). Twenty-seven healthy males performed 1 of 4
      bench press workouts described by the 1 repetition maximum (1RM) load: 4 sets of
      maximum repetitions at 50%-1RM (50%-1RM RES), 5 sets of maximum repetitions at
      75%-1RM (75%-1RM RES), 10 sets of maximum repetitions at 90%-1RM (90%-1RM RES),
      or 8 sets of maximum repetitions at 110%-1RM (110%-1RM RES). Each RES was equated
      by the total volume of load lifted (repetitions x sets x load). Blood samples,
      collected pre-exercise (Pre) and post-exercise (Post) at 1 and 24 hours (24 h),
      were analyzed for total and free testosterone, total cortisol, and CK. In
      general, testosterone and cortisol showed little change within or between the
      different RES (p > 0.05), possibly because of the relatively low volume lifted
      and/or the small muscle mass activated by the bench press exercise. Cortisol was
      elevated after the 75%-1RM RES at the Post sample, with this response also
      exceeding the other RES (p < 0.05). The 24 h CK response was also elevated after
      the 75%-1RM RES (p < 0.05), thereby suggesting greater training strain for the
      same volume of load. These results confirm previous recommendations regarding the
      prescription of resistance exercise and the importance of total volume as a
      stimulus for activating the endocrine system and achieving long-term adaptation.

PMID- 19855325
TI  - Optimizing exercise outcomes: the efficacy of resistance training using
      conventional vs. novel movement arcs.
AB  - The purpose of this study was to examine the effect of using multidirectional
      movement arcs in a resistance training program for the shoulder. It was
      hypothesized that multidirectional exercises performed against resistance would
      result in a greater positive adaptation of the muscle tissue than conventional
      movement patterns commonly used in strength training. Fourteen female athletes
      were initially assessed using a 1x repetition maximum (1xRM) test for shoulder
      flexion and shoulder abduction (dominant and nondominant arm). After
      randomization into 2 groups, subjects engaged in different strength training
      programs against Thera-Band resistance for 6 weeks. Follow-up testing was then
      completed. Group A was assigned a strength training program that used
      conventional curvilinear movement arcs. Group B completed resistance training
      that comprised multidirectional exercises. Both the conventional and novel
      strength training programs induced improvements in the 1x RM test (p < 0.01).
      There was a trend toward greater improvements in the nonconventional training
      group, but this was statistically insignificant. This suggests that varying the
      axial or torsional loading of muscle fibers during strength training may confer
      further benefit to conventional methods of training variation. Consequently,
      further studies are indicated to investigate if resistance training that
      incorporates multidirectional movement arcs is more effective than those used in
      conventional strength training programs. This may have implications on the design
      of future training programs that aim to optimize strength gains.

PMID- 19855326
TI  - Effect of resistance exercise on percent body fat using leg-to-leg and segmental
      bioelectrical impedance analysis in adults.
AB  - The purpose of this study was to examine the effect of a resistance exercise bout
      on percent body fat (%BF) measured by leg-to-leg and segmental bioelectrical
      impedance analysis (LBIA; SBIA) in adults. Eighty-six volunteers (45 women; 41
      men) reported to the weight training facility on 2 separate occasions. After an
      initial LBIA and SBIA assessment, subjects performed 60 minutes of continuous
      resistance exercise, or did nothing, which served as the control. During the
      resistance exercise trial, subjects completed an 8-exercise circuit protocol
      consisting of 3 sets of 10 to 12 repetitions at 65-75% of 1 repetition maximum
      for each exercise. Subjects were provided with a bottle of water for consumption
      during both trials. Body composition was reassessed 60 minutes after baseline for
      comparison. For the resistance exercise trial, significant reductions (p < 0.05)
      in SBIA-measured %BF (women = 0.9 +/- 1.0%; men = 1.4 +/- 0.8%) and impedance
      (women = 22.2 +/- 17.0 Omega; men = 22.3 +/- 10.0 Omega) were observed, whereas
      LBIA body composition measurements remained unchanged. After the control trial,
      significant increases (p < 0.05) in SBIA-measured %BF (women = 0.6 +/- 0.8%; men
      = 0.5 +/- 0.7%) and impedance (women = 7.8 +/- 12.6 Omega; men = 4.7 +/- 8.3
      Omega) and LBIA-measured %BF (women = 0.4 +/- 0.7%; men = 0.4 +/- 0.5%) were
      observed because of the body mass gain (approximately 300-400 g) after drinking.
      When using SBIA, assessments should be performed before resistance exercise to
      eliminate exercise-induced alterations in %BF. Conversely, resistance exercise
      had no effect on the LBIA measurements, and, therefore, following pretest
      exercise guidelines may not be necessary when this technology is used for the
      body composition assessment.

PMID- 19855327
TI  - Electromyographic analysis of three different types of lat pull-down.
AB  - The purpose of this work was to evaluate the activity of the primary motor
      muscles during the performance of 3 lat pull-down techniques through surface
      electromyography (EMG). Twenty-four trained adult men performed 5 repetitions of
      behind-the-neck (BNL), front-of-the-neck (FNL), and V-bar exercises at 80% of 1
      repetition maximum. For each technique, the root mean square from the EMG signal
      was registered from the pectoralis major (PM), latissimus dorsi (LD), posterior
      deltoid (PD), and biceps brachii (BB) and further normalized in respect to that
      which presented the highest value of all the techniques. A series of two-way
      repeated measures analysis of variance was used to compare the results, with
      Tukey-Kramer as the post hoc test and alpha = 0.05. During the concentric phase,
      PM value showed the FNL to be significantly higher than V-bar/BNL and V-bar
      higher than BNL. During the eccentric phase, FNL/V-bar was higher than BNL. For
      LD, there was no difference between techniques. PD presented BNL higher than
      FNL/V-bar and FNL higher than V-bar in the concentric phase and BNL higher than V
      bar in the eccentric phase. BB exhibited BNL higher than V-bar/FNL and V-bar
      higher than FNL in both concentric and eccentric phases. Considering the main
      objectives of lat pull-down, we concluded that FNL is the better choice, whereas
      BNL is not a good lat pull-down technique and should be avoided. V-bar could be
      used as an alternative.

PMID- 19855328
TI  - Familiarization indexes in sessions of 1-RM tests in adult women.
AB  - The objective of this study was to evaluate the familiarization to the 1
      repetition maximum (1-RM) test in adult women with previous experience in
      resistance training and to compare the statistical methods to analyze
      familiarization. Twenty-seven women, with previous experience in resistance
      training but detrained for 6 months, participated in the study (21.6 +/- 2.5
      years; 59.1 +/- 6.7 kg; 1.65 +/- 0.04 m; 21.8 +/- 2.4 kg/m). The 1-RM test was
      used to verify the strength levels in 3 exercises: bench press, squat, and arm
      curl. Five 1-RM tests sessions were performed in distinct days. Analysis of
      variance (ANOVA) for repeated measures, intraclass correlation coefficient (ICC),
      and Bland-Altman plotting procedures were used to compare the 1-RM load between
      the familiarization sessions. The significance assumed was p < 0.05. All
      exercises presented good ICC between 1-RM familiarization sessions (0.97-0.98).
      However, there were significant increases in 1-RM load among the 5 sessions of 1
      RM tests in the bench press (+5.7%), squat (+5.4%), and arm curl (+11.1%). In
      addition, there were different responses according to the statistical analyses
      used (ANOVA, higher 1-RM strength, and Bland-Altman plotting). The results of the
      present study suggest that familiarization sessions are important for an accurate
      assessment of 1-RM load even in subjects with previous experience in resistance
      training.

PMID- 19855329
TI  - Neuromuscular performance of elite rugby union players and relationships with
      salivary hormones.
AB  - This study compared the neuromuscular performance (speed, power, strength) of
      elite rugby union players, by position, and examined the relationship between
      player performance and salivary hormones, by squad and position. Thirty-four
      professional male rugby players were assessed for running speed (10-m, 20-m or 30
      m sprints), concentric mean (MP) and peak power (PP) during a 70-kg squat jump
      (SJ) and 50-kg bench press throw (BT), and estimated 1 repetition maximum (1RM)
      strength for a box squat (BS) and bench press (BP). Tests were performed on
      separate days with absolute and normalized (power and strength only) values
      computed. Saliva was collected before each test and assayed for testosterone (Sal
      T) and cortisol (Sal-C). In absolute terms, the backs demonstrated greater speed
      and BT MP, whereas the forwards produced greater SJ PP and MP and BS 1RM (p <
      0.01). However, BT, SJ and BS performances were no different when normalized for
      body mass in kg (p > 0.05). A comparison (absolute and normalized) of BT PP
      showed no positional differences (p > 0.05), whereas BP 1RM was greater for the
      forwards (p < 0.05). These results may be attributed to genetic and/or training
      factors relating to the positional demands of rugby. The Sal-T and/or Sal-C
      concentrations of players correlated to speed, power, and strength, especially
      for the backs (p < 0.05), thereby confirming relationships between neuromuscular
      performance and hormone secretion patterns. Based on these findings, it was
      suggested that training to increase whole-body and muscle mass might facilitate
      general performance improvements. Training prescription might also benefit from
      acute and chronic hormone monitoring to identify those individuals likely to
      respond more to hormonal change.

PMID- 19855330
TI  - Youth versus adult "weightlifting" injuries presenting to United States emergency
      rooms: accidental versus nonaccidental injury mechanisms.
AB  - Resistance training has previously been purported to be unsafe and ineffective in
      children. The purpose of this investigation was to evaluate resistance training
      related injuries presenting to U.S. emergency rooms by age, type, and mechanism
      of injury. We hypothesized that older athletes would sustain greater percentages
      of joint sprains and muscle strains, whereas younger athletes would sustain a
      greater percentage of accidental injuries that would result in an increased
      percentage of fractures in youths. The U.S. Consumer Product Safety Commission
      (CPSC) National Electronic Injury Surveillance System was queried from 2002 to
      2005 using the CPSC code for "Weightlifting." Subjects between the ages of 8 and
      30 were grouped by age categories 8 to 13 (elementary/middle school age), 14 to
      18 (high school), 19 to 22 (college), and 23 to 30 (adult). Injuries were
      classified as "accidental" if caused by dropped weight or improper equipment use.
      Multiple logistic regression was used to compare accidental injuries between age
      groups. The sample consisted of 4,111 patients. Accidental injuries decreased (p
      < 0.05) with age: 8 to 13 > 14 to 18 > 19 to 22 years = 23 to 30 years.
      Conversely, sprain/strain injuries increased in each successive age group (p <
      0.05). Evaluation of only the nonaccidental injuries (n = 2,565) showed that the
      oldest categories (19-22 and 23-30 yr) demonstrated a greater percentage of
      sprains and strains relative to younger age categories (p < 0.001). Two thirds of
      the injuries sustained in the 8 to 13 group were to the hand and foot and were
      most often related to "dropping" and "pinching" in the injury descriptions, and
      there was an increased percentage of fractures in the 8 to 13 group relative to
      all other groups (p < 0.001). The study findings indicate that children have
      lower risk of resistance training-related joint sprains and muscle strains than
      adults. The majority of youth resistance training injuries are the result of
      accidents that are potentially preventable with increased supervision and
      stricter safety guidelines.

PMID- 19855332
TI  - Acute effects of various whole body vibration frequencies on 1RM in trained and
      untrained subjects.
AB  - The purpose of this study was to compare the acute effects of whole body
      vibration (WBV) at different vibration frequencies on 1 repetition maximum (1RM)
      in recreationally strength trained subjects and untrained subjects. While
      performing a 1RM test in half squat, trained (8 men) and untrained (5 men and 3
      women) subjects were randomly exposed to WBV with a frequency of 20 Hz, 35 Hz, 50
      Hz (amplitude, 3 mm), or control conditions with no vibration. 1RM in half squat
      was assessed in a Smith Machine while subjects were standing on a vibration
      platform. Both untrained and recreationally strength trained subjects increased
      their 1RM at a vibration frequency of 50 Hz compared with no vibration (p <
      0.05), and untrained subjects increased their 1RM to a larger extent than
      recreationally trained subjects (8.7% vs. 4.9%; p < 0.05). However, there was no
      difference in 1RM while vibrating at a frequency of 20 Hz and 35 Hz compared with
      no vibrations in either of the groups. In conclusion, WBV with a frequency of 50
      Hz increases 1RM in both recreationally strength trained and untrained subjects,
      whereas vibration frequencies of 20 Hz and 35 Hz do not have this effect.
      Untrained subjects increased their 1RM at WBV at 50 Hz to a larger extent than
      recreationally strength trained subjects. Therefore, if the purpose is to
      increase the stimulus to the neuromuscular system to a greater extent than
      traditional strength training, the WBV frequency should be 50 Hz and the
      exercises should be heavily loaded (as in traditional strength training).

PMID- 19855331
TI  - Sex differences in "weightlifting" injuries presenting to United States emergency
      rooms.
AB  - Benefits of resistance training include improved muscle strength and sports
      performance and may include reduced injuries. However, few studies have examined
      sex differences in resistance training-related injuries. The objective of this
      investigation was to evaluate sex differences in injuries associated with
      strength training in adolescents and young adults by type (sprains and strains,
      fractures), mechanism (accidental, nonaccidental), and location (head, trunk,
      arm, hand, leg, foot) of injury. We hypothesized that there would be sex
      differences in type, mechanism, and location of strength training injuries. The
      U.S. Consumer Product Safety Commission (CPSC) National Electronic Injury
      Surveillance System (NEISS) was queried from 2002 to 2005 using the CPSC code for
      "Weightlifting." Subjects between the ages of 14 and 30 years were included in
      the study. CPSC sampling weights were used to calculate national estimates from
      the sample of 3,713 patients (men = 3,102; women = 611). Weighted Chi-square
      analyses were used to compare differences in mechanism, type, and location of
      injury for men versus women. Men had significantly more sprains and strains (p =
      0.004), whereas women demonstrated increased accidental injuries compared to men
      (p < 0.001). The trunk was the most commonly injured body part for both men
      (36.9%) and women (27.4%). Men had more trunk injuries than women (p < 0.001),
      whereas women had more foot (p < 0.001) and leg (p = 0.03) injuries than men (p <
      0.001). The findings indicate that men may suffer more exertional-type resistance
      injuries during strength training (sprains and strains) compared to women,
      especially at the trunk. Conversely, women may be more susceptible to lower
      extremity injuries resulting from accidents during resistance training.

PMID- 19855333
TI  - Acute and cumulative effects of different times of recovery from whole body
      vibration exposure on muscle performance.
AB  - This experiment was designed to assess the acute (Study I) and cumulative
      response (Study II) of muscle performance to differing recovery times after
      exposure to whole body vibration (WBV). All subjects (mean age 19.7 +/- 1.9) were
      healthy and physically active. In both studies, subjects were exposed to a WBV
      bout of 6 exposures of 60 seconds each, with frequency of 30 Hz and amplitude of
      4 mm. In Study I, subjects (n = 30) underwent 3 trials (1 per day) on different
      days with a 2-day wash-out period between trials; each trial included either a 1,
      2, or 3 minutes of recovery between exposures to WBV. All subjects underwent all
      trials, which were randomly assigned. Jump ability and muscle power were measured
      before and after each bout. In Study II, subjects (n = 45) underwent 12 sessions
      of WBV training in 4 weeks (3 bouts/wk). The subjects were randomly assigned to 1
      of the following 3 groups: WBV with 1-minute recovery periods between exposures,
      WBV with 2-minute recovery periods between exposures, or control group. Jump
      ability, muscle power, and strength were measured before and after each bout. In
      the acute study (I), recovery times of 1 and 2 minutes enhanced all measured
      parameters (p < 0.05), with the 2-minute recovery being more effective. In the
      long-term study (II), however, although both periods also enhanced the measured
      parameters (p < 0.05), the 1-minute recovery proved more effective because the
      response was modified by systematic stimulation. In conclusion, 2-minute recovery
      periods provided the most effective acute enhancement of muscle activation,
      whereas the 1-minute recovery provided a more effective cumulative enhancement of
      muscle power and jump ability.

PMID- 19855334
TI  - Traditional exercises do not have a significant impact on abdominal peak force in
      healthy young adults.
AB  - The abdominals are vital to activities of daily living, for the prevention of
      lumbar pathologies, and during sport performance. The purpose of this study was
      to determine if training without external resistance was a sufficient overload to
      improve abdominal strength as defined by peak force. Seventy-one healthy men and
      women (age 19-40 years) participated in the 11-week study. Subjects were matched
      on baseline abdominal strength and then randomly assigned to 1 of 3 categories
      based on the number of days they performed abdominal exercises (0 days, 3 days,
      or 6 days per week). The results indicated that performing abdominal exercises 3
      or 6 times per week did not improve either concentric or eccentric strength.
      These results suggest that the exercises used during this study were not enough
      of a stimulus to significantly improve concentric or eccentric strength values in
      either exercise group.

PMID- 19855335
TI  - Quantifying differences in the "fat burning" zone and the aerobic zone:
      implications for training.
AB  - The primary objective of this study was to examine the relationship of the "fat
      burning" and aerobic zones. Subjects consisted of 36 relatively fit runners (20
      male, 16 female) who completed a maximal exercise test to exhaustion on a motor
      driven treadmill. The lower and upper limit of the "fat burning" zone was
      visually assessed by examining each individual graph. Maximal fat oxidation (MFO)
      was determined to be that point during the test at which fat metabolism in fat
      calories per minute peaked. The lower limit of the aerobic zone was assessed as
      50% of heart rate reserve, whereas the upper limit was set at anaerobic
      threshold. Although the lower and upper limits of the "fat burning" zone (67.6
      87.1% maximal heart rate) were significantly lower (p < 0.05) than their
      counterparts in the aerobic zone (58.9-76.2%), the considerable overlap of the 2
      zones would indicate that training for fat oxidation and training for aerobic
      fitness are not mutually exclusive and may be accomplished with the same training
      program. Furthermore, it was determined that this training program could
      simultaneously meet the requirements of the American College of Sports Medicine
      for both aerobic fitness and weight control. Maximal fat oxidation occurred at
      54.2% maximal oxygen uptake (VO2max). However, the great variability in response
      between individuals would preclude the prediction of both the "fat burning" zone
      and MFO, indicating a need for measurement in the laboratory. If laboratory
      testing is not possible, the practitioner or subject can be reasonably confident
      MFO lies between 60.2% and 80.0% of the maximal heart rate.

PMID- 19855336
TI  - Twelve-month training-induced changes in elite international volleyball players.
AB  - The purpose of this investigation was to examine the strength, power, and
      anthropometric contributors to vertical jump performances that are considered
      specific to volleyball success, including countermovement vertical jump (CMVJ)
      and spike jump (SPJ), by examining changes across 12 months in elite volleyball
      players. Anthropometry (height, mass, summation Sigma 7 skinfolds), vertical jump
      ability (CMVJ, SPJ, and depth jumps from 35 cm), kinetic and kinematic data from
      an unloaded and loaded (body mass + 50%) jump squat were assessed before and
      after 12 months of training in 20 elite male volleyball players. To examine the
      association between the change in each of the strength, power, and anthropometric
      variables with the changes in CMVJ and SPJ, a correlation analysis of the percent
      change of each variable with the percent change in CMVJ and SPJ was performed. A
      significant correlation (r = 0.47; p = 0.04) was observed between changes in CMVJ
      and SPJ. Significant (p = 0.006-0.02) improvements in CMVJ were associated with
      increased peak force in the unloaded (r = 0.61) and loaded jump squat (r = 0.59)
      and greater relative power and peak velocity in the loaded jump squat (r = 0.49
      and 0.51, respectively). The significant increase in CMVJ was strongly associated
      (r = 0.865; p < 0.001) with an improved depth-jump ability. Significant (p =
      0.003-0.03) increases in SPJ were related to increases in relative power (r =
      0.64), peak force (r = 0.46), and peak velocity (r = 0.49) in the loaded jump and
      improved depth-jumping ability (r = 0.591). This study demonstrates that, in an
      elite population of volleyball players, stretch-shortening cycle performance and
      the ability to tolerate high stretch loads, as in the depth jump, are critical to
      improving jumping performance.

PMID- 19855337
TI  - The effect of a rhythmic gymnastics program on the dynamic balance ability of
      individuals with intellectual disability.
AB  - The purpose of this study was to examine the effect of a rhythmic gymnastics
      program on the dynamic balance ability of a group of adults with intellectual
      disability (ID). The sample consisted of 18 adults with ID. The control group
      consisted of 8 adults and an intervention group of 10. The subjects were assigned
      to each group according to their desire to participate or not in the intervention
      program. Both groups were comparable in terms of age, weight, height, IQ, and
      socioeconomic background. The intervention group received a 12-week rhythmic
      gymnastics program at a frequency of 3 lessons per week, of 45 minutes. The
      methods of data collection included pre/post-test measurements of the dynamic
      balance for all subjects of both groups. The dynamic balance ability was measured
      by means of a balance deck (Lafayette) and was determined by the number of
      seconds the subject could remain standing on the platform of the stabilometer in
      durations of 30-, 45-, and 60-second intervals. As the results indicated, the
      intervention group showed a statistically significant improvement (p < 0.05) in
      terms of dynamic balance ability in each interval after the application of the
      rhythmic gymnastics program when compared with the control group. It is concluded
      that adults with ID can improve their balance ability with the application of a
      well-designed rhythmic gymnastics program.

PMID- 19855338
TI  - Noninvasive determination of anaerobic threshold by monitoring the %SpO2 changes
      and respiratory gas exchange.
AB  - The purpose of this study was to determine the validity of noninvasive anaerobic
      threshold (AT) estimation using %SpO2 (arterial oxyhemoglobin saturation) changes
      and respiratory gas exchanges. Fifteen active, healthy males performed 2 graded
      exercise tests on a motor-driven treadmill in 2 separated sessions. Respiratory
      gas exchanges and heart rate (HR), lactate concentration, and %SpO2 were measured
      continuously throughout the test. Anaerobic threshold was determined based on
      blood lactate concentration (lactate-AT), %SpO2 changes (%SpO2-AT), respiratory
      exchange ratio (RER-AT), V-slope method (V-slope-AT), and ventilatory equivalent
      for O2 (EqO2-AT). Blood lactate measuring was considered as gold standard
      assessment of AT and was applied to confirm the validity of other noninvasive
      methods. The mean O2 corresponding to lactate-AT, %SpO2-AT, RER-AT, V-slope -AT,
      and EqO2-AT were 2176.6 +/- 206.4, 1909.5 +/- 221.4, 2141.2 +/- 245.6, 1933.7 +/-
      216.4, and 1975 +/- 232.4, respectively. Intraclass correlation coefficient (ICC)
      analysis indicates a significant correlation between 4 noninvasive methods and
      the criterion method. Blond-Altman plots showed the good agreement between O2
      corresponding to AT in each method and lactate-AT (95% confidence interval (CI).
      Our results indicate that a noninvasive and easy procedure of monitoring the
      %SpO2 is a valid method for estimation of AT. Also, in the present study, the
      respiratory exchange ratio (RER) method seemed to be the best respiratory index
      for noninvasive estimation of anaerobic threshold, and the heart rate
      corresponding to AT predicted by this method can be used by coaches and athletes
      to define training zones.

PMID- 19855339
TI  - Acute effects of various weighted bat warm-up protocols on bat velocity.
AB  - Although research has provided evidence of increased muscular performance
      following a facilitation set of resistance exercise, this has not been
      established for use prior to measuring baseball bat velocity. The purpose of this
      study was to determine the effectiveness of selected weighted bat warm-up
      protocols to enhance bat velocity in collegiate baseball players. Nineteen
      collegiate baseball players (age = 20.15 +/- 1.46 years) were tested for upper
      body strength by a 3-repetition maximum (RM) bench press (mean = 97.98 +/- 14.54
      kg) and mean bat velocity. Nine weighted bat warm-up protocols, utilizing 3
      weighted bats (light = 794 g; standard = 850 g; heavy = 1,531 g) were swung in 3
      sets of 6 repetitions in different orders. A control trial involved the warm-up
      protocol utilizing only the standard bat. Pearson product correlation revealed a
      significant relationship between 3RM strength and pretest bat velocity (r = 0.51,
      p = 0.01). Repeated measures analysis of variance (ANOVA) revealed no significant
      treatment effects of warm-up protocol on bat velocity. However, the order of
      standard, light, heavy bat sequence resulted in the greatest increase in bat
      velocity (+6.03%). These results suggest that upper-body muscle strength
      influences bat velocity. It appears that the standard, light, heavy warm-up order
      may provide the greatest benefit to increase subsequent bat velocity and may
      warrant use in game situations.

PMID- 19855340
TI  - Validity of a nomogram to predict long distance running performance.
AB  - The purpose was to test the validity of a nomogram to predict performance at
      distances ranging from the 10 km to the marathon. Official running rankings of
      the French Athletics Federation for the men's 10 km, 20 km, and marathon were
      scrutinized from 2002 to 2006. Performances of runners who competed in the 3
      distances during the same year were noted (n = 330). Predicted performance by the
      nomogram was obtained for each distance from the performance at 2 other
      distances. Actual and predicted performances were compared by a Wilcoxon matched
      pairs test. The magnitude of the difference was assessed by the effect size (ES).
      Correlation and Bland-Altman plots were used to evaluate the association and the
      level of agreement between actual and predicted performances. The nomogram
      overestimated performance at the 10-km distance (13 seconds; p = 0.03) and
      underestimated performance at the 20-km distance (27 seconds; p < 0.01). The
      overestimation for the marathon was not significant (85 seconds; p = 0.06).
      Whatever the distance, ES were trivial (-0.04 < ES < 0.05). Correlations were
      0.89 for the 10 km and the marathon and 0.97 for the 20 km. The limits of
      agreement represented 10.2, 6.1, and 13.2% of the mean of actual and predicted
      performances in 10 km, 20 km, and marathon, respectively. These results support
      the validity of the nomogram to predict performance on 10 km, 20 km, and marathon
      from the performance at 2 other distances. The accuracy of predictions is better
      when performance is interpolated. Given their validity and accuracy, interpolated
      predictions of the nomogram may be used to prescribe realistic training
      intensities during tempo runs, but also to determine the optimal strategy during
      the race.

PMID- 19855341
TI  - Functional balance training in collegiate women athletes.
AB  - This study examined the effects of functional balance training implemented in
      addition to regular season practice, competition, and strength and conditioning
      training for collegiate women athletes. Twenty-six members of National Collegiate
      Athletic Association (NCAA) Division I collegiate women's volleyball and soccer
      teams volunteered. A pre-test, post-test group design was used for the study. Pre
      and post-test measures were the following: Skindex, body mass index (BMI),
      single-leg squat, prone quadra-ped core test, Biodex balance test, and a 1-minute
      sit-up test. The intervention consisted of 10 minutes of Indo Board (a dynamic
      balance board) training 4 days a week throughout the entire season. The
      volleyball team served as the intervention group, whereas the soccer team had no
      intervention. A dependent t-test demonstrated a statistically significant (p <or=
      0.05) improvement on the single-leg squat and 1-minute sit-up test for the
      volleyball team, whereas the soccer team (no intervention) demonstrated a
      statistically significant (p <or= 0.05) improvement on the 1-minute sit-up test.
      It was concluded that by training on an unstable surface, the individual is
      conditioning the core while simultaneously performing balance activities. It was
      also noted that, although improvements were seen, each participant (both
      volleyball and soccer) was also active in regular season practice, competition,
      and strength and conditioning training over the course of the season. Functional
      balance activities are cost effective and should be added to any form of strength
      and conditioning program in an attempt to enhance program effectiveness and to
      develop functional postural activation. Functional postural activation will not
      only assist with functional performance, but also in the prevention of injury.

PMID- 19855342
TI  - Factors affecting flutter kicking speed in women who are competitive and
      recreational swimmers.
AB  - The purpose of this study was to determine the relationships between possible
      predictive measures of a 50 m front crawl swimming and a 22.86 m flutter kicking
      speed. Ten women who were National Collegiate Athletic Association Division I
      collegiate swimmers and 10 women who were recreational swimmers (mean +/- SD =
      20.6 +/- 1.6 years; 66.7 +/- 10.3 kg; 166.7 +/- 8.8 cm) volunteered for the
      study. Anthropometric measures were obtained including height, leg length, lower
      leg length, and foot length. Ankle flexibility was assessed by measuring ankle
      plantar flexion and ankle inversion. Lower body power was measured using a
      vertical jump. Swimming and kicking speed were measured as the time to complete a
      50 m front crawl and a 22.86 m flutter kick, respectively. Significant moderate
      correlations were demonstrated between ankle plantar flexion and flutter kicking
      speed (r = 0.509); age and 22.86 m kick time (r = 0.608); age and 50 m swim time
      (r = 0.476); and 50 m swim time and 22.86 m kick time (r = 0.790). No significant
      correlations were observed between any of the anthropometric measurements or
      vertical jump power with either kicking or swimming speed. As anecdotally noted
      by swim coaches over the years, this study provides some actual data showing that
      ankle flexibility significantly influences flutter kick capability. Surprisingly,
      vertical jump power and body size were not strong predictors of kicking or
      swimming speed in this group of subjects. Strength and conditioning coaches, swim
      coaches, and athletes should evaluate and carefully develop ankle flexibility to
      positively contribute to kicking capabilities.

PMID- 19855343
TI  - Effect of plyometric training on swimming block start performance in adolescents.
AB  - This study aimed to identify the effect of plyometric training (PT), when added
      to habitual training (HT) regimes, on swim start performance. After the
      completion of a baseline competitive swim start, 22 adolescent swimmers were
      randomly assigned to either a PT (n = 11, age: 13.1 +/- 1.4 yr, mass: 50.6 +/-
      12.3 kg, stature: 162.9 +/- 11.9 cm) or an HT group (n = 11, age: 12.6 +/- 1.9
      yr, mass: 43.3 +/- 11.6 kg, stature: 157.6 +/- 11.9 cm). Over an 8-week preseason
      period, the HT group continued with their normal training program, whereas the PT
      group added 2 additional 1-hour plyometric-specific sessions, incorporating
      prescribed exercises relating to the swimming block start (SBS). After completion
      of the training intervention, post-training swim start performance was
      reassessed. For both baseline and post-trials, swim performance was recorded
      using videography (50 Hz Canon MVX460) in the sagital plane of motion. Through
      the use of Silicon Coach Pro analysis package, data revealed significantly
      greater change between baseline and post-trials for PT when compared with the HT
      group for swim performance time to 5.5 m (-0.59 s vs. -0.21 s; p < 0.01) and
      velocity of take-off to contact (0.19 ms vs. -0.07 ms; p < 0.01). Considering the
      practical importance of a successful swim start to overall performance outcome,
      the current study has found that inclusion of suitable and safely implemented PT
      to adolescent performers, in addition to HT routines, can have a positive impact
      on swim start performance.

PMID- 19855344
TI  - A comparison of two stretching modalities on lower-limb range of motion
      measurements in recreational dancers.
AB  - Most stretching techniques are designed to place a "stress" on the
      musculoskeletal unit that will increase its resting length and range of motion
      (ROM). Twenty-four adolescent dancers participated in a 6-week intervention
      program that compared low-intensity stretching (Microstretching) with moderate
      intensity static stretching on active and passive ranges of motion.
      Microstretching is a new modality that reduces the possibility of the
      parasympathetic system being activated. Repeated measures analysis indicated
      changes in ROM over the intervention period (p < 0.05), with the Microstretching
      group demonstrating greater increases in passive and active ROM than the static
      stretch group (p < 0.01); there was no noted bilateral differences in ROM. The
      results from this study agree with past studies that have found that stretching
      increases the compliance of any given muscle and therefore increases the range of
      motion. One main finding of the present study was that throughout a 6-week
      training program very-low-intensity stretching had a greater positive effect on
      lower-limb ROM than moderate-intensity static stretching. The most interesting
      aspect of the study was the greater increase in active ROM compared to passive
      ROM by the Microstretching group. This suggests that adaptation has occurred
      within the muscle itself to a greater extent than in structures of the hip joint.
      Practical application for this technique suggests it is beneficial as a
      postexercise modality that potentially has a restorative component.

PMID- 19855345
TI  - Acute effect of static stretching on rate of force development and maximal
      voluntary contraction in older women.
AB  - The purpose of this study was to investigate, in older women, the acute effect of
      static stretching (SS) on both muscle activation and force output. Twenty-three
      older women (64.6 +/- 7.1 yr) participated in the study. The maximal voluntary
      contraction (MVC), rate of force development (RFD) (50, 100, 150, and 200 ms
      relative to onset of muscular contraction), and peak RFD (PRFD) (the steepest
      slope of the curve during the first 200 ms) were tested under 2 randomly separate
      conditions: SS and control (C). Electromyographic (EMG) activity of the vastus
      medialis (VM), vastus lateralis (VL), and biceps femoris (BF) muscles also was
      assessed. The MVC was significantly lower (p < 0.05) in the 3 trials of SS when
      compared with the C condition (control: 925.0 +/- 50.9 N; trial 1: 854.3 +/- 55.3
      N; trial 2: 863.1 +/- 52.2 N; and trial 3: 877.5 +/- 49.9 N). PRFD showed a
      significant decrease only for the first 2 trials of SS when compared with the C
      condition (control: 2672.3 +/- 259.1 N/s; trial 1: 2296.6 +/- 300.7 N/s; and
      trial 2: 2197.9 +/- 246.3 N/s). However, no difference was found for RFD (50,
      100, 150, and 200 ms relative to onset of muscular contraction). The EMG activity
      for VM, VL, and BF was not significantly different between the C and SS
      conditions. In conclusion, the older women's capacity to produce muscular force
      decreased after their performance of SS exercises. The mechanisms responsible for
      this effect do not appear to be related to muscle activation. Thus, if
      flexibility is to be trained, it is recommended that SS does not occur just
      before the performance of activities that require high levels of muscular force.

PMID- 19855346
TI  - Effects of static stretching in warm-up on repeated sprint performance.
AB  - The aim of this study was to examine the effects of static stretching during warm
      up on repeated sprint performance and also to assess any influence of the order
      in which dynamic activities (i.e., run-throughs and drills) and static stretching
      are conducted. Thirteen male team sport players completed a repeated sprint
      ability test consisting of three sets of maximal 6 x 20-m sprints (going every 25
      seconds) after performing one of three different warm-up protocols in a within
      subjects counterbalanced design. Each warm-up protocol involved an initial 1000-m
      jog, followed by either dynamic activities only (D), static stretching followed
      by dynamic activities (S-D), or dynamic activities followed by static stretching
      (D-S). First (FST), best (BST) and total (TST) 20-m sprint times were determined
      for each individual set of the repeated sprint ability test and overall (3 sets
      combined). Although consistent significant differences were not observed between
      trials for TST, BST, and FST, the mean values for TST in all individual sets and
      overall were generally slowest in the D-S condition (D = 60.264 +/- 1.127
      seconds; S-D = 60.347 +/- 1.774 seconds; D-S = 60.830 +/- 1.786 seconds). This
      trend was supported by moderate to large effect sizes and qualitative indications
      of "possible" or "likely" benefits for TST, BST, and FST for the D and S-D warm
      ups compared to D-S. No significant differences or large effect sizes were noted
      between D and S-D, indicating similar repeated sprint ability performance.
      Overall, these results suggest that 20-m repeated sprint ability may be
      compromised when static stretching is conducted after dynamic activities and
      immediately prior to performance (D-S).

PMID- 19855347
TI  - Aerobic fitness in futsal players of different competitive level.
AB  - Recently the use of small-sided games (mainly 5 vs. 5) proved to be a valid
      training method to improve aerobic fitness in soccer. Thus, it could be
      hypothesized that professional futsal (soccer 5-a-side indoor version) players
      may possess a well-developed aerobic fitness as a consequence of training and
      game participation. The aim of this study was to examine maximal oxygen uptake
      (VO2max), ventilatory threshold (VT), and running economy (RE, VO2 at 8 kmxh) of
      futsal players of different competitive levels to determine whether aerobic
      fitness is a discriminative variable for futsal success. Subjects were 24 male
      futsal players from a professional top-ranked second division team (PT, n = 11)
      and a semi-professional top-ranked third division team (ST, n = 13). Aerobic
      fitness was assessed with a running protocol performed on a motor-driven
      treadmill. Professional team and ST players' VO2max were 62.9 +/- 5.3 and 55.2 +/
      5.7 mLxkgxmin, respectively (p < 0.05). RE was 34.1 +/- 2.7 and 32.4 +/- 2.7
      mLxkgxmin for PT and ST, respectively (p >0.05). PT and ST attained VT at 70.5 +/
      2.7 and 71.3 +/- 5.2% of VO2max, respectively (p > 0.05). Results showed that
      VO2max may be considered a competitive-level dependent physical variable in
      futsal. VO2max values of or above 60 mLxkgxmin are advisable to play futsal at
      the professional level.

PMID- 19855348
TI  - Test-retest reliability and minimal detectable change of the hexagon agility
      test.
AB  - The purpose of this study was to examine the test-retest reliability and minimal
      detectable change (MDC95) of the hexagon test. The hexagon test is a routinely
      used measure of agility in the sports and rehabilitation professions, yet its
      reliability has not been investigated in prior research. A total of 26 college
      aged men (n = 17) and women (n = 9) of various activity levels were recruited to
      participate in 3 testing sessions: baseline, 1 hour after baseline, and 48 hours
      after baseline. The results of this study indicated excellent test-retest
      reliability for both same-day intraclass correlation coefficient (ICC) model 3,1
      = 0.938 and between-day ICC (3,1) = 0.924 analyses. The MDC95 for the hexagon
      test was 1.015 seconds. A significant difference in the mean times was identified
      during the same-day test-retest sessions (p < 0.001) but not the between-day test
      retest sessions (p = 0.18). The significant differences identified between the
      baseline and the same-day retest session suggests a learning effect. The hexagon
      test shows excellent reliability for measuring agility, which supports its use as
      a tool to assess athletic performance and lower-extremity agility. Evidence of
      reliability, in addition to its ease of administration, makes the hexagon test a
      practical and effective method to measure agility. When using this test as a
      measure of agility, a change of greater than 1.015 seconds is necessary to be 95%
      certain that the change in time reflects improvement and exceeds measurement
      error. A practice trial is recommended prior to recording scores to attenuate the
      possibility of a learning effect.

PMID- 19855349
TI  - Morphologic heterogeneity of human thymic nonlymphocytic cells.
AB  - The thymus is the central organ of the immune system. It is essential for the
      development and maintenance of normal immune system, especially cell-mediated
      immunity. From the morphological point of view, the thymus is divided into two
      main compartments, cortex and medulla. The thymic microenvironment consists of a
      network of reticular epithelial cells and other fixed and free cells. The
      microenvironment of thymus is very important for the selection and maturation of
      T cells. T cell differentiation occurs via T cell receptors. The major
      histocompatibility complex participates in interactions between T cells and
      thymic epithelial cells, in addition to interactions between T cells and
      dendritic cells, macrophages and myoid cells. The neuroendocrine system regulates
      early T cell differentiation by the transcription of neuroendocrine genes in the
      stromal network and expression of cognitive receptors by immature T cells. This
      work briefly summarizes morphological and ultrastructural characteristics of
      thymic epithelial cells, dendritic cells, macrophages and myoid cells. It is
      accompanied by the authors' own photomicrographs and electronmicrograph from a
      transmission electron microscope. All of these cells play a critical role in the
      proliferation, differentiation and selection of precursor cells in the T-cell
      lineage, but the precise mechanisms not well understudood.

PMID- 19855350
TI  - A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET)
      in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is
      not only ineffective and not evidence-based, but also potentially harmful for
      many patients with ME/CFS.
AB  - Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a
      debilitating disease which, despite numerous biological abnormalities has
      remained highly controversial. Notwithstanding the medical pathogenesis of
      ME/CFS, the (bio)psychosocial model is adopted by many governmental organizations
      and medical profes-sio-nals to legitimize the combination of Cognitive Behavioral
      Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this
      model CBT and GET aim at eliminating presumed psychogenic and socially induced
      maintaining factors and reversing deconditioning, respectively. In this review we
      invalidate the (bio)psychosocial model for ME/CFS and demonstrate that the
      success claim for CBT/GET to treat ME/CFS is unjust. CBT/GET is not only hardly
      more effective than non-interventions or standard medical care, but many patients
      report that the therapy had affected them adversely, the majority of them even
      reporting substantial deterioration. Moreover, this review shows that exertion
      and thus GET most likely have a negative impact on many ME/CFS patients. Exertion
      induces post-exertional malaise with a decreased physical performan-ce/aerobic
      capacity, increased muscoskeletal pain, neurocognitive impairment, "fatigue", and
      weakness, and a long lasting "recovery" time. This can be explained by findings
      that exertion may amplify pre-existing pa-thophysiological abnormalities
      underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and
      nitrosative stress, channelopathy, defec-tive stress response mechanisms and a
      hypoactive hypothalamic-pituitary-adrenal axis. We conclude that it is unethical
      to treat patients with ME/CFS with ineffective, non-evidence-based and
      potentially harmful "rehabilitation therapies", such as CBT/GET.

PMID- 19855351
TI  - Chronic fatigue syndrome: la bete noire of the Belgian health care system.
AB  - The World Health Organization acknowledges Myalgic Encephalomyelitis (ME)/Chronic
      Fatigue Syndrome (CFS) to be a medical illness. ME/CFS is characterized by
      disorders in the inflammatory and oxidative and nitrosative stress (IO&NS)
      pathways. In 2002, the Belgian government started with the development of CFS
      "Reference Centers", which implement a "psychosocial" model. The medical
      practices of these CFS Centers are defined by the Superior Health Council, e.g.
      treatment should be based upon Cognitive Behavioral Therapy (CBT) and Graded
      Exercise Therapy (GET); and biological assessments and treatments of ME/CFS
      should not be employed. Recently, the Belgian government has evaluated the
      outcome of the treatments at the CFS Centers. They concluded that a
      "rehabilitation therapy" with CBT/GET yielded no significant efficacy in the
      treatment of ME/CFS and that CBT/GET cannot be considered to be curative
      therapies. In case reports, we have shown that patients who were "treated" at
      those CFS centers with CBT/GET in fact suffered from IO&NS disorders, including
      intracellular inflammation, an increased translocation of gram-negative
      enterobacteria (leaky gut), autoimmune reactions and damage by O&NS. Considering
      the fact that these findings are exemplary for ME/CFS patients and that GET may
      even be harmful, it means that many patients are maltreated by the Belgian CFS
      Centers. Notwithstanding the above, the government and the CFS Centers not only
      continue this unethical and immoral policy, but also reinforce their use of
      CBT/GET in patients with ME/CFS treated at those Centers.

PMID- 19855352
TI  - Complete objective response of oesophageal squamocellular carcinoma to biological
      treatment.
AB  - The synergetic use of Somatostatin, Melatonin, Retinoids, Vitamins C, D3, and E,
      Calcium, sulphated Aminoglucosides, and minimum doses of cyclophosphamide in a 70
      year old male patient with inoperable scarcely differentiated oesophageal
      carcinoma, has provided, from the beginning of treatment in 1995 to the present
      date, an excellent quality of life, as well as a cure with functional recovery.
      This paper discusses the rationale and molecular action mechanisms of the
      treatment which has a differentiating, apoptotic anti-proliferation effect,
      preserving and enhancing, unlike chemo- and/or radiotherapy, both the trophic and
      functional capacity of organs and tissues, and immunity and antiblastic
      homeostasis. This result confirms the efficacy of this biological multiple
      treatment (MDB); it is also in line with the positive results already published
      on the use of MDB in low-grade NHL (66) and in stage 3 or 4 lung carcinomas (53).
      The MDB, with no need for hospitalisation, no toxicity and without in the least
      reducing working activity, gradually and slowly reduced, and then eliminated the
      tumour formation. According to the author, reporting this case is useful in order
      to call for greater interest in the possibilities offered to oncology by the MDB
      biological and receptor treatment.

PMID- 19855353
TI  - Congenital hypothyroidism simulating acromegaly - a diagnostic pitfall.
AB  - Since introduction of population-based neonatal screening for congenital
      hypothyroidism (CH), cases of long-term untreated inborn hypothyreosis have
      become very rare whereas its clinical symptoms are currently not well known. We
      report a patient with CH due to an ectopic thyroid. The presented case is
      exceptional due to both advanced age of diagnosis and unusual clinical
      presentation, as the anomaly was detected during evaluation of suspected
      acromegaly at the age of 62. This report indicates that there is still necessity
      of considering, in spite of its rarity, congenital form in differential diagnosis
      of hypothyroidism.

PMID- 19855354
TI  - Two patients with eating disorders treated by naltrexone.
AB  - According to a recent literature review on the opioid mechanism in eating
      disorders, we found that there is increasing reason to re-examine the treatment
      potential of naltrexone. The endogenous opioid system belongs to the important
      modulators of food intake. The eating disorders share many traits with substance
      dependence models. We present two case histories of time-limited naltrexone
      therapy to show that, in clinical practice, individualized indication may
      contribute to short-term improvement and to prediction of a different long-term
      treatment outcome.

PMID- 19855355
TI  - The effectiveness of choline citrate infusions monitored by lymphocyte
      transformation test (LTT) in multiple sclerosis. A new approach to the diagnosis
      and treatment of the disease.
AB  - The efficacy of intravenous choline citrate infusions was investigated in 34
      patients with multiple sclerosis (MS) by clinical evaluation and by monitoring of
      lymphocyte proliferation in vitro against fragments of myelin basic protein (MOG
      35-55, MBP15-31, PLP 39-15) over a period of 12 weeks. Patients have been
      diagnosed with MS at least one year before entering the study and suffered from
      mild relapsing/remitting course to long-term chronic progressive disease. Twenty
      one patients exhibited positive lymphocyte proliferation to myelin fragments
      prior to treatment and were therefore selected for further studies. Choline
      citrate was administered with a dosage of 1200mg/ 2x week for a period of 3
      months. This treatment resulted in a significant decrease of lymphocyte
      proliferation to neural fragments (MOG- 35-55, MBP15-31) in lymphocyte
      transformation test (LTT). There was no significant SI change of PLP Peptide (PLP
      39-15) LTT found after treatment with choline citrate. During the 3 mo
      observation period, patients remained stable and no side-effects of the treatment
      were observed. In addition, some patients reported long-lasting improvement (less
      paresthesia and increase of muscle strength in lower extremities) which was
      demonstrated up to 3 years later. In one spectacular case a commercial pilot was
      able to return to duty again after treatment. This pilot was allowed back in to
      his position as a commercial flying cockpit member and is on duty for more than 4
      yrs now.

PMID- 19855356
TI  - Oxytocin and carbetocin effects on spontaneous behavior of male rats: modulation
      by oxytocin receptor antagonists.
AB  - OBJECTIVES: Oxytocin (OXY) in addition to peripheral actions has many central
      regulatory functions which can be studied on animal models. In the present study
      we examined in rats, which behavioral actions of OXY and long-acting carba-analog
      of OXY carbetocin (CBT) in the open-field can be inhibited by OXY-receptor
      antagonists. Our interest focused on the behavioral patterns considered
      indicative of anxiety-related behavior. To determine what is the participation of
      OXY receptor on OXY and CBT induced behavioral changes, we used two peptide and
      one nonpeptide OXY antagonists differing in selectivity for OXY receptor.
      METHODS: OXY, CBT as well as OXY antagonists were injected intraperitoneally, and
      spontaneous behavior (horizontal and vertical activity, grooming) of Wistar rats
      was observed in the circular open-field arena 60 min after application of drugs;
      in some experiments testing was performed without treatment few days after drug
      administration. RESULTS: OXY at the dose 0.05 mg/kg increased locomotion
      indicating anxiety attenuation, but 1.0 mg/kg reduced both locomotion and
      rearing. CBT in the dose range 0.1-3.0 mg/kg either did not change or increased
      horizontal activity. The increase in exploration after both peptides persisted
      for several days. A marked difference in the behavioral effects of the two
      peptides was grooming enhancement induced by OXY compared with the absence of
      this effect after CBT. The increase of the activity induced by OXY and CBT
      indicating anxiolytic-like action was blocked by OXY antagonists. However, the
      reduction of exploration induced by 1.0 mg dose of OXY was only partially
      reversed. The OXY induced enhanced grooming was completely antagonized by all
      used antagonists. CONCLUSIONS: Behavioral effects of OXY and its antagonists
      after their i.p. application indicate that they penetrate blood brain barrier.
      The diversity in potency of OXY antagonists to inhibit grooming and other
      behaviors induced by OXY suggests that receptors participating in these behaviors
      may differ in brain localization, receptor conformation and/or in the utilized
      signaling pathways.

PMID- 19855357
TI  - Serotonin receptor 2A gene polymorphisms and schizophrenia: association with
      family history, diagnostic subtype and height in patients.
AB  - OBJECTIVES: The 102T/C single nucleotide polymorphism (SNP) in the 5
      hydroxytryptamine receptor 2A (HTR2A) gene has been reported to be associated
      with schizophrenia. However, SNPs of the HTR2A gene other than the 102T/C have
      attracted only limited studies in relation to schizophrenia, and also on the
      whole SNPs of the HTR2A gene have been little studied in relation to clinical
      parameters in patients. Therefore, the aim of this study was to evaluate the
      impact of main functionally characterized SNPs of the HTR2A gene on both the
      schizophrenia and clinical parameters. METHODS: Ninety-four patients with
      schizophrenia and 57 control subjects were genotyped for the -1438A/G, -783A/G,
      102T/C and His452Tyr SNPs of the HTR2A gene. The four SNPs were then investigated
      in relation to the schizophrenia and clinical parameters. RESULTS: No differences
      were found in genotype-, allele- or haplotype frequencies between schizophrenia
      patients and control subjects. However, the 452Tyr variant of the His452Tyr
      polymorphism occurred more often in patients with a family history of
      schizophrenia compared with patients without heredity (p=0.028). The 452Tyr
      variant was also more common in female patients with paranoid schizophrenia than
      in those with non-paranoid schizophrenia (p=0.018). Moreover, the male patients
      carrying the A/A or T/T genotypes of the -1438A/G and 102T/C polymorphisms were
      shorter than those carrying the G/A or C/T genotypes (p=0.007; p=0.006).
      CONCLUSION: The present findings bring further support to the view that the 
      1438A/G, 102T/C and His452Tyr polymorphisms of the HTR2A gene are connected with
      a constitutive cellular change that causes susceptibility to schizophrenia.

PMID- 19855358
TI  - Guaifenesin enhances the analgesic potency of ibuprofen, nimesulide and celecoxib
      in mice.
AB  - OBJECTIVES: Previously, we found that guaifenesin enhances analgesia induced by
      paracetamol. The aim of the present study was to determine whether guaifenesin is
      able to also increase analgesic activity in the non-steroid anti-inflammatory
      drugs ibuprofen, nimesulide and celecoxib. In addition we investigated the
      influence of guaifenesin on plasma levels of nimesulide. METHODS: A model of
      visceral pain consisting of intraperitoneal injection of acetic acid (writhing
      test) was used. Levels of nimesulide in plasma were measured by HPLC. All drugs
      were given orally and tested in mice. RESULTS: Guaifenesin alone did not produce
      any antinociceptive effect. Simultaneous administration of guaifenesin (200
      mg/kg) and subanalgesic doses of ibuprofen (10 and 30 mg/kg), nimesulide (10 and
      20 mg/kg) or celecoxib (1 and 5 mg/kg) resulted in a significant antinociceptive
      effects. The plasma levels of nimesulide were significantly higher in combination
      with guaifenesin at 30, 60 and 90 min after oral administration in comparison to
      nimesulide monotherapy. CONCLUSION: The present results suggest that guaifenesin
      might enhance the analgesic activity of various non-steroidal anti-inflammatory
      drugs.

PMID- 19855359
TI  - Relation between functional polymorphism of catalase gene (-262C>T) and recurrent
      depressive disorder.
AB  - Numerous studies have provided information indicating the involvement of
      oxidative stress in the pathophysiology of depressive disorder (DD). The
      antioxidative system protects against the effects caused by reactive oxygen
      species (ROS). Catalase (CAT) is one of antioxidative enzymes observed to change
      their levels in the course of depression. The enzyme decomposes hydrogen peroxide
      (H(2)O(2)), whose overproduction is a result of many processes taking place in
      depression. Therefore, functional polymorphism of the CAT gene can be a candidate
      marker of the risk of depression. The presented study assessed the correlation
      between -262C>T polymorphism of the CAT gene, which influences the increase of
      CAT expression and activity, and the risk of depression development. The study,
      carried out on a homogeneous group recruited from the Polish population, enrolled
      149 healthy subjects and 149 depressive patients. The groups were age-matched.
      The obtained results indicate no correlation between -262C>T polymorphism of the
      CAT gene (both with respect to genotype distribution and allele frequency) and
      the risk of depression. Nevertheless, further studies assessing the correlations
      between depression and polymorphism of the genes encoding antioxidative enzymes
      on larger groups of subjects should be undertaken.

PMID- 19855360
TI  - Treatment and outcome of patients after cardiopulmonary resuscitation admitted to
      the intensive cardiac care unit.
AB  - OBJECTIVES: Sudden circulatory arrest is most often of cardiac origin. Our aim
      was to evaluate circulatory arrest etiology and treatment strategies in patients
      after cardiopulmonary resuscitation (CPR) with persistent impairment of
      consciousness in relation to survival and the subsequent quality of life. DESIGN:
      Retrospective analysis of patients after CPR treated according to the local
      protocol including mild hypothermia in the intensive cardiac care unit. RESULTS:
      Over 2 years, we admitted 57 mechanically ventilated patients after CPR. 47
      patients (82%) were resuscitated outside the hospital. In 33 patients (58%) the
      initial rhythm was ventricular fibrillation; in the remaining patients (42%)
      asystole/pulseless electrical activity. Urgent coronary angiography was performed
      in 36 patients and percutaneous coronary intervention in 25 of them. The
      admission APACHE II score was 32,4 +/- 3,4 with predicted mortality of 77,1%. The
      hospital survival rate was 54% and 47% of the patients were discharged home in a
      good state of health (Glasgow outcome score 4-5). CONCLUSION: Our results suggest
      that comprehensive post-resuscitation care including therapeutic hypothermia and
      percutaneous coronary intervention in selected cases may have a positive impact
      on the prognosis of patients after CPR.

PMID- 19855361
TI  - 7-Hydroxylated derivatives of dehydroepiandrosterone in the human ventricular
      cerebrospinal fluid.
AB  - OBJECTIVE: Dehydroepiandrosterone is a long established neuroactive steroid. Some
      authors documented that 7-oxygenated derivatives of this steroid may be
      responsive at least by part for its physiological activity. METHODS: In the
      ventricular cerebrospinal fluid obtained from 15 patients with hydrocephalus (8
      postmenopausal women and 7 men) potentially neuroactive steroid 7-oxygenated
      derivatives of dehydroepiandrosterone were quantified using gas
      chromatography/mass spectrometry. RESULTS: Besides free dehydroepiandrosterone 7
      oxygenated steroids such as 7alpha- and 7beta-hydroxy-dehydroepiandrosterone, 5
      androstene-3beta,7alpha,17beta-triol and 5-androstene-3beta,7beta,17beta-triol in
      picomolar concentration in serum and cerebrospinal fluid were found. CONCLUSION:
      Dehydroepiandrosterone and its 7-oxygenated derivatives are present in
      ventricular cerebrospinal fluid in concentration 2 -100 times lower than in
      serum.

PMID- 19855362
TI  - The effect of laparotomy on hydroxyl radicals, singlet oxygen and antioxidants
      measured by EPR method in the tails of rats.
AB  - OBJECTIVES: The aim of the study was to demonstrate that direct measurement of
      hydroxyl radicals and singlet oxygen in the tail of living rats is possible. The
      basic level of hydroxyl radicals and singlet oxygen were measured and the effects
      of antioxidants on their levels were studied in the tail of living anaesthetized
      rats after acute postoperative pain. Laparotomy was performed as the source of
      acute abdominal pain. After closure of the abdominal cavity, the animals began to
      awaken within 30-60 minutes. They were left to recover for 2-3 hours; then they
      were reanesthetized and the effect of antioxidants was measured on the numbers of
      hydroxyl radicals and singlet oxygen via blood in the tail. METHODS: The
      laparotomy was preformed under general anesthesia (Xylazin and Ketamin) using
      Wistar rats. After recovery and several hours of consciousness they were
      reanaesthetized and free radicals and singlet oxygen were measured. An
      antioxidant mixture (vitamins A, C, D and Selenium) was administered
      intramuscularly prior to the laparotomy. All measurements were done on the tail
      of anaesthetized animals. In this particular article, the effect of antioxidants
      is only reported for hydroxyl radicals. RESULTS: After laparotomy, which
      represented both somatic and visceral pain, hydroxyl radicals and singlet oxygen
      were increased. Antioxidant application prior to laparotomy decreased the numbers
      of hydroxyl radicals. CONCLUSION: Results are in agreement with our previous
      finding regarding the increase in hydroxyl free radicals and singlet oxygen
      following nociceptive stimulation, in this case a combination of both somatic and
      visceral pain. The administered antioxidants mitigated the increase. This is
      further confirmation that direct measurement of free radicals and singlet oxygen
      represents a very useful method for the biochemical evaluation of pain and
      nociception.

PMID- 19855363
TI  - Anthropometric changes in non-medicated ADHD boys.
AB  - OBJECTIVES: The aim of the study is to compare complex anthropometric
      characteristics in non medicated boys with ADHD and normal population. METHODS:
      Complex anthropometric examination of non-medicated ADHD boys (n=46, average age
      11.03 years), statistical and clinical comparison to the actual population growth
      norm. In contrast to the most of the previous studies, which analyzed mostly only
      BMI or basic signs of growth as height and weight, the presented study operates
      with a complex anthropometrical measurement and comparison with actual population
      norm. RESULTS: The results of the study show significant differences in the signs
      of nutrition (percentage of fat) and growth indicators (lower values of height)
      between ADHD and non ADHD children. Further anthropometrical parameters show
      other possible but in the studied sample statistically non-significant
      differences. CONCLUSION: Many studies analyzed growth relation to medication of
      ADHD children, but did not consider that the changes could appear also in non
      medicated children and thus they might not be only a side effect of the treatment
      but a manifestation of the disorder itself. Growth changes in non-medicated
      children are not described well enough, so the presented study was performed to
      compare anthropometrics characteristics in ADHD boys with norm of nonclinical
      population and specify the differences. The results points to hypothesis that the
      growth changes are primarily caused by the disorder itself.

PMID- 19855364
TI  - The occurrence of thyroid focal lesions and a need for fine needle aspiration
      biopsy in patients with acromegaly due to an increased risk of thyroid cancer.
AB  - OBJECTIVE: The high prevalence of goiter in acromegalic patients is well known.
      Several studies revealed increased frequency of thyroid carcinoma in these
      patients. The aim of the study was to evaluate the incidence of thyroid lesions,
      including thyroid cancer in acromegalic patients and to estimate possible factors
      influencing their occurrence, especially high IGF-1 level. MATERIALS AND METHODS:
      86 consecutive patients with acromegaly were retrospectively analyzed. 45
      patients had been previously treated for acromegaly and 41 were newly diagnosed.
      In all subjects hGH, IGF-1, TSH, FT4 levels were determined. Thyroid gland was
      evaluated in ultrasound examination. Fine needle aspiration biopsy (FNAB) was
      performed in every solid or mixed thyroid nodule. RESULTS: Thyroid morphology
      abnormalities were found in 75 patients (87.2%). 10 patients (11.6%) had diffuse
      goiter and 65 patients (75.6%) had nodular goiter. There were 5 cases of thyroid
      carcinoma (5.8%): 3 papillary carcinomas and two follicular variants of papillary
      cancer. Out of five cancers three were multifocal, one infiltrated thyroid
      capsule and one was diagnosed at the stage of metastases to four lymph nodes.
      CONCLUSIONS: Our study confirmed common co-existence of acromegaly and thyroid
      lesions. Furthermore, it revealed considerably high occurrence of thyroid
      carcinoma in these patients. In view of this correlation, the potential role of
      IGF-1 in pathogenesis of benign and malignant thyroid neoplasms should be
      considered. Due to high frequency of thyroid cancer in acromegalic patients, we
      suggest to perform fine needle aspiration biopsy in each case of thyroid nodule.

PMID- 19855365
TI  - Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in
      depressive women.
AB  - BACKGROUND: Depressive disorder (DD) is associated with an increased risk of type
      2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested,
      that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such
      as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial
      hypertension and elevated fasting glycaemia, could stand behind the connection.
      Recent findings have shown, that adipocytokines leptin and adiponectin might play
      a role in both depression and MetS. AIM: The aim of this pilot study was to
      observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin
      ratio and indices of IR in women with depressive disorder. MATERIALS AND METHODS:
      The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and
      indices of IR were investigated in a group of 38 women with DD. The results were
      compared with those of 38 healthy women of the control group, matched for age.
      RESULTS: Depressive women differed significantly from the controls in higher
      concentrations of plasma leptin (p <0.05), insulin (p <0.01), C-peptide (p
      <0.01), value of HOMA-IR (p <0.01), and the leptin-to-adiponectin ratio (p
      <0.05).The QUICKI index of insulin sensitivity was lower (p <0.01). HAM-D score
      of DD cases correlated negatively with adiponectin (r = - 0.3505; p < 0.05),
      independently of HOMA-IR. We have not found in DD group any differences between
      the drug free patients and those treated either with escitaloprame alone or in
      the combination with mirtazapine. CONCLUSIONS: The results of the pilot study
      presented support the hypothesis that at least part of DD cases has increased
      leptin serum levels and certain features of MetS. It could be the factor
      connecting depression with an increased risk of either DM2 or CVD.

PMID- 19855366
TI  - Paliperidon mediated modification of cortical inhibition.
AB  - Transcranial magnetic stimulation is a neurophysiological method which enables
      direct quantitative in vivo assessment of cortical excitability and inhibition.
      The aim of the study was to assess the impact of paliperidone on the motor
      threshold and cortical silent period, in a drug-naive patient, with first episode
      schizophrenia using this technique. Paliperidone monotherapy caused a significant
      reduction of severity of schizophrenic symptomatology in the patient. At the same
      time, a significant prolongation of the cortical silent period, from 118.68 ms
      before to 185.13 ms after therapy, occurred. Because the cortical silent period
      is a function of GABA(B) receptors, we can assume that paliperidone may have the
      ability to enhance GABA(B) receptor-mediated neurotransmission.

PMID- 19855367
TI  - Sweat: a potential marker of clinical activity in panic disorder.
AB  - OBJECTIVE: Panic disorder (PD) is a paroxysmal neuropsychiatric disorder with
      unclear etiology and obscure pathophysiology. Despite the frequency of its
      occurrence, PD still has no reliable laboratory markers. The sweat is a neglected
      human secrete reacting immediately to various neurovegetative challenges
      including psychic imupulses. We hypothesized a possible dysfunction of sweat
      homeosthasis in PD. SUBJECTS AND METHODS: 10 patients with active PD, 9 patients
      with PD in remission and 11 age-matched controls participated in this study. All
      subjects underwent a single 8-min session in the dry-heat sauna. Sweat and venous
      blood have been collected immediately after the end of this session.
      Concentrations of lactate, glucose, creatinine, natrium, potassium, chlorine,
      calcium and magnesium have been quantitatively estimated in both liquids and
      compared statistically among three groups. RESULTS: We did not find any
      significant difference in blood parameters of the three above groups. However,
      the patients with active PD had significantly higher sweat levels of lactate,
      glucose, creatinine and magnesium than both the other groups which did not
      differ. Moreover, sweat concentrations of natrium, potassium and chlorine were
      significantly higher in active PD comparing to the group of PD patients in
      remission. CONCLUSIONS: The sweat of patients with active PD in comparison to PD
      in its clinical remission exhibits surprisingly distinctive changes of selected
      parameters after dry-heat sauna exposure. Increased concentrations of lactate,
      glucose and magnesium in the sweat are not contradictory with presupposed
      neurotransmitter-metabolic firing mechanisms in PD. These findings appear to be
      perspective biochemical markers in PD and its course.

PMID- 19855368
TI  - Doppler velocimetry of the materno-fetal circulation in preterm delivered
      pregnancies complicated with hypertension.
AB  - BACKGROUND: Hypertension is one of the most frequent complications of pregnancy.
      Due to high risk of morbidity and mortality in both mothers and children, it is
      necessary to continuously monitor the pregnancy, principally with biophysical
      methods. Particularly, doppler velocimetry of the materno-fetal circulation
      proves useful. THE AIM of the study was to assess the usefulness of doppler test
      in monitoring the condition of the foetus in preterm delivered pregnancy
      complicated with hypertension. MATERIAL AND METHODS: The retrospective analysis
      comprised the data of 116 women who delivered prematurely at the Clinics of the
      Department of Gynaecology and Obstetrics at the Collegium Medicum of the
      Jagiellonian University in the years 2006-2007, resulting in creation of Group I
      involving 38 pregnant women with preeclampsia, and Group II of 36 women whose
      pregnancy was complicated with gestational hypertension. Control group was formed
      of 42 women with correct arterial blood pressure. When describing the groups, the
      differences in the birth weight and Apgar score were indicated. RESULTS: A
      significant statistical difference was found in the area of pulsation rate in the
      umbilical artery and cerebro-placental ratio (CPR). In the case of preterm
      delivery complicated with arterial pressure disorders, the foetus is
      characterised with worse organic perfusion and slower somatic growth than if no
      concomitant hypertension is present. Hypertension forms an additional risk factor
      in the course of preterm delivery, and doppler velocimetry is a good method for
      monitoring the condition of the foetus, as it allows for detection of
      irregularities and for implementation of relevant treatment to improve the
      newborn's condition at birth.

PMID- 19855369
TI  - An assessment of the so called point of reversibility of dementia syndrome in
      making an effective prognosis for continued use of medication.
AB  - BACKGROUND: An effort to share our many years of clinical experience. OBJECTIVE:
      To predict the effectiveness of medication in advanced phases of dementia in the
      light of pharmaceutical economics and to find the most suitable alternative
      treatments. METHODS: Use of 3 commonly available geriatric tests Mini-Mental
      State Examination (MMSE), Activity of Daily Living (ADL) and Instrumental
      Activity of Daily Living (IADL). Threshold values of these tests, after
      mathematical transformation to comparable values, enables calculation of the
      hypothetical Point of Reversibility Pr found on the range here called MEKO.
      RESULTS: Estimated values of SD can be used to choose the most effective medical
      treatment. CONCLUSION: Beyond the upper threshold of S(D), on the basis of the
      above mentioned method, continued medication is of dubious value.

PMID- 19855370
TI  - Borna disease virus circulating immunocomplex positivity and psychopathology in
      psychiatric patients in the Czech Republic.
AB  - OBJECTIVES: Borna disease virus (BDV) is an RNA virus belonging to the family
      Bornaviridae. BDV is a neurotropic virus that causes changes in mood, behaviour
      and cognition. Patients with psychiatric disorders have a higher incidence of BDV
      positivity than healthy individuals. METHODS: We examined the seropositivity of
      BDV circulating immunocomplexes (CIC) in psychiatric patients and healthy
      individuals (blood donors). We examined 39 psychiatric inpatients for the
      presence of BDV CIC in the serum by ELISA on day 0, 28 and 56. During the same
      period psychopathology was measured using psychiatric scales (CGI, CGI-I, MADRS,
      SDS, PANSS). This is the first such study performed in the Czech Republic.
      RESULTS: BDV CIC positivity was detected in 66.7% of psychiatric patients (26/39)
      on day 0, in 53.9% (14/26) on day 28 and in 52.9% on day 56 (9/17). The control
      group was 22.2% (28/126) positive. The incidence of BDV CIC was significantly
      higher in psychiatric patients than in healthy individuals (p=0.001). The
      significantly higher level of BDV CIC was associated with the higher severity of
      psychopathology in comparison with patients with mild or moderate psychopathology
      (p=0.03). We did not find any association between BDV CIC positivity and other
      characteristics (age, diagnosis, family, personal history, the history of
      infectious diseases, contact with animals). CONCLUSION: In our study psychiatric
      patients had significantly higher levels of BDV CIC than the control group. The
      highest levels of BDV CIC were detected in patients with more severe
      psychopathology.

PMID- 19855371
TI  - ELIME (enzyme linked immuno magnetic electrochemical) method for mycotoxin
      detection.
AB  - Immunoassays are a valid alternative to the more expensive and time consuming
      quantitative HPLC or GC(1, 2) methods for the screening detection of hazardous
      mycotoxins in food commodities. In this protocol we show how to fabricate and
      interrogate an electrochemical competitive Enzyme linked immunomagnetic assay
      based on the use of magnetic beads as solid support for the immunochemical
      chain(3) and screen printed electrodes as sensing platform. Our method aims to
      determine the total amount of HT-2 and T-2 toxins, mycotoxins belonging to the
      trichothecenes family and of great concern for human health(4). The use of an
      antibody clone with a cross reactivity of 100% towards HT-2 and T-2 allows to
      simultaneously detect both toxins with similar sensitivity(5). The first step of
      our assay is the coating step where we immobilize HT2-KLH conjugate toxin on the
      surface of magnetic beads. After a blocking step, necessary to avoid non-specific
      absorptions, the addition of a monoclonal antibody allows the competition between
      immobilized HT-2 and free HT-2 or T-2 present in the sample or dissolved in a
      standard solution. At the end of the competition step, the amount of monoclonal
      antibody linked to the immobilized HT-2 will be inversely proportional to the
      amount of toxin in the sample solution. A secondary antibody labeled with
      alkaline phosphatase (AP) is used to reveal the binding between the specific
      antibody and the immobilized HT-2. The final measurement step is performed by
      dropping an aliquot of magnetic bead suspension, corresponding to a specific
      sample/standard solution, on the surface of a screen-printed working electrode;
      magnetic beads are immobilized and concentrated by means of a magnet placed
      precisely under the screen-printed electrode. After two minutes of incubation
      between magnetic beads and a substrate for AP, the enzymatic product is detected
      by Differential Pulse Voltammetry (DPV) using a portable instrument (PalmSens)
      also able to initiate automatically eight measurements within an interval of few
      seconds.

PMID- 19855372
TI  - Cellular encapsulation in 3D hydrogels for tissue engineering.
AB  - The 3D encapsulation of cells within hydrogels represents an increasingly
      important and popular technique for culturing cells and towards the development
      of constructs for tissue engineering. This environment better mimics what cells
      observe in vivo, compared to standard tissue culture, due to the tissue-like
      properties and 3D environment. Synthetic polymeric hydrogels are water-swollen
      networks that can be designed to be stable or to degrade through hydrolysis or
      proteolysis as new tissue is deposited by encapsulated cells. A wide variety of
      polymers have been explored for these applications, such as poly(ethylene glycol)
      and hyaluronic acid. Most commonly, the polymer is functionalized with reactive
      groups such as methacrylates or acrylates capable of undergoing crosslinking
      through various mechanisms. In the past decade, much progress has been made in
      engineering these microenvironments - e.g., via the physical or pendant covalent
      incorporation of biochemical cues - to improve viability and direct cellular
      phenotype, including the differentiation of encapsulated stem cells (Burdick et
      al.). The following methods for the 3D encapsulation of cells have been optimized
      in our and other laboratories to maximize cytocompatibility and minimize the
      number of hydrogel processing steps. In the following protocols (see Figure 1 for
      an illustration of the procedure), it is assumed that functionalized polymers
      capable of undergoing crosslinking are already in hand; excellent reviews of
      polymer chemistry as applied to the field of tissue engineering may be found
      elsewhere (Burdick et al.) and these methods are compatible with a range of
      polymer types. Further, the Michael-type addition (see Lutolf et al.) and light
      initiated free radical (see Elisseeff et al.) mechanisms focused on here
      constitute only a small portion of the reported crosslinking techniques. Mixed
      mode crosslinking, in which a portion of reactive groups is first consumed by
      addition crosslinking and followed by a radical mechanism, is another commonly
      used and powerful paradigm for directing the phenotype of encapsulated cells
      (Khetan et al., Salinas et al.).

PMID- 19855373
TI  - Quantitative evaluation of CpG island methylation in hyperplastic polyps.
AB  - Microsatellite unstable cancers account for up to 15% of sporadic colon cancers
      and are predominantly located in the proximal colon. These cancers commonly show
      MLH1 promoter methylation and the CpG island methylator phenotype (CIMP). A
      potential precursor of sporadic unstable cancers, the proximal hyperplastic
      polyp, is also reported to have CIMP and MLH1 methylation. However, this latter
      finding is not supported by MLH1 protein expression studies. To help resolve this
      apparent discrepancy, we determined MLH1 promoter methylation and CIMP by
      quantitative real-time PCR for 29 proximal hyperplastic polyps, 23 distal
      hyperplastic polyps, and 11 sporadic microsatellite unstable colon cancers. BRAF
      V600E mutation status was also determined. Positive methylation was defined as
      the percentage of methylated reference (PMR) >10. Only 1 of 29 proximal
      hyperplastic polyps showed positive MLH1 methylation (PMR of 13.0). Neither this
      polyp nor seven other proximal polyps with PMR values between 0 and 10 showed
      loss of MLH1 protein expression by immunohistochemistry. In contrast, all 11
      microsatellite unstable cancers showed high degrees of MLH1 methylation, with PMR
      values >30. Fourteen of twenty-nine (48%) of the proximal hyperplastic polyps and
      1 of 23 (4%) of the distal hyperplastic polyps showed CIMP (P<0.001). Of the
      unstable cancers, 10 of 11 showed CIMP. The PMR values in the CIMP-positive
      proximal hyperplastic polyps were significantly lower than those of the unstable
      cancers for 4 of the 5 CIMP markers (P<0.05). BRAF V600E mutations were seen in
      83% of proximal and 74% of distal hyperplastic polyps. Quantitative analysis of
      MLH1 methylation does not support earlier reports of MLH1 methylation in proximal
      hyperplastic polyps. However, these lesions do harbor promoter methylation at
      other CIMP loci, although at a lower level than that seen in unstable cancers. If
      these polyps are the precursor for sporadic microsatellite unstable cancers, then
      MLH1 methylation and higher degrees of promoter methylation in general occur at a
      later stage of carcinogenesis.

PMID- 19855374
TI  - Expression of gastric pyloric mucin, MUC6, in colorectal serrated polyps.
AB  - Serrated polyps of the colorectal mucosa represent a heterogeneous and
      controversial taxonomic category with variation in histopathological, molecular,
      and immunohistochemical characteristics and with an incomplete understanding of
      pathogenesis. A previous study reported that the expression of gastric pyloric
      type mucin, MUC6, characterized sessile serrated adenomas. We therefore evaluated
      the expression of MUC6 in serrated polyps identified among 2502 participants in a
      Phase III chemoprevention trial within the Arizona Cancer Center Colorectal
      Cancer Prevention Trials Program and characterized the associated
      histopathological features and location. We carried out immunohistochemistry for
      MUC6 on 146 serrated lesions and 87 conventional tubular adenomas, and assessed
      the percentage of cells with expression and the grade of staining intensity. In
      all 92 hyperplastic polyps, 43 sessile serrated adenomas, and 11 traditional
      serrated adenomas were included. Polyps ranged in size from 1-150 mm. The
      association of MUC6 staining with serrated polyp category was evaluated using
      classification and regression tree (CART) analysis and two-sided Fisher's exact
      test. A total of 53% of sessile serrated adenomas (n=23), 17% of hyperplastic
      polyps (n=16), and 18% of traditional serrated adenomas (n=2), but none of 87
      tubular adenomas, expressed MUC6. Expression was limited to the lower crypts in
      all serrated polyps. The extent of positive staining ranged from 2-100% of crypt
      cells and was independent of the histopathological type. MUC6 expression had
      relatively high specificity for sessile serrated adenoma (82%) but low
      sensitivity (54%). In CART analysis, proximal location was found to be the best
      partitioning factor for MUC6, followed by classification as sessile serrated
      adenoma. We conclude that MUC6 expression is strongly associated with proximal
      location of serrated polyps, but only has modest utility as a tissue biomarker
      for sessile serrated adenoma.

PMID- 19855375
TI  - Clinicopathological predictors of EGFR/KRAS mutational status in primary lung
      adenocarcinomas.
AB  - Screening for EGFR and KRAS mutations in patients with lung adenocarcinomas can
      be used to predict the patient's response to EGFR tyrosine kinase inhibitors, but
      there is a lack of guidelines for testing in clinical practice. We analyzed the
      morphological and clinicopathological characteristics, including tumor stage,
      size, presence of scar, inflammatory response, angiolymphatic and pleural
      invasion, of 345 surgically treated primary lung adenocarcinomas with respect to
      their EGFR and KRAS mutational profile and EGFR FISH. EGFR and KRAS mutations
      were found in 33 (10%) and 78 (23%) of lung adenocarcinomas, respectively,
      whereas 226 (67%) cases were negative for both mutations. There was a large
      overlap in the analyzed clinicopathological characteristics among the three study
      groups. Statistically significant predictors for the presence of EGFR mutations
      included history of never smoking (OR 5.939; 95% Wald confidence limit 1.662
      21.223, P=0.0149), mild lymphocytic host response (OR 4.724; 95% Wald confidence
      limit 1.33-1.776; P=0.0163), female gender (OR 2.571; 95% Wald confidence limit
      1.015-6.511, P=0.0463) and absence of solid growth pattern. Statistically
      significant predictors for the presence of KRAS mutations included older age (OR
      1.034; 95% Wald confidence limit 1.007-1.062, P=0.0132), history of smoking (OR
      0.617, 95% Wald confidence limit 0.357-1.066, P=0.0412) and mucinous
      differentiation. EGFR FISH positivity as defined by the Colorado criteria was a
      significant predictor of EGFR mutations, with high polysomy as the strongest
      predictive criteria. Despite statistically significant differences among the
      study groups and because of the large overlap in the analyzed clinicopathological
      criteria, none of these could be implemented as the selection criteria for
      molecular testing in clinical practice. The cost-effectiveness of lung carcinoma
      mutational testing would be improved by initial determination of KRAS mutational
      status as negative predictor of the patient's response to EGFR tyrosine kinase
      inhibitors, followed by EGFR mutational analysis, if necessary.

PMID- 19855376
TI  - Collagenous sprue is not always associated with dismal outcomes: a
      clinicopathological study of 19 patients.
AB  - Collagenous sprue is associated with high morbidity; however, the etiology of
      this disorder is unclear. Data regarding the pathological and clinical
      manifestations of patients with collagenous sprue are also limited. We, thus,
      undertook this study to gain insight into the etiology, disease manifestations
      and outcomes of collagenous sprue. We searched our departmental database (1999
      2008) to identify cases of collagenous sprue and to obtain clinical and
      laboratory data. Small bowel histology, including thickness of subepithelial
      collagen, intra-epithelial lymphocyte phenotype and results of T-cell clonality
      assays were evaluated. Nineteen patients (15 women, 4 men, age 22-80 years, mean
      57 years) were identified. Seventeen (89%) had celiac disease and two had
      unclassified sprue; 9 of 17 (53%) celiac disease patients had refractory disease;
      5 of 15 (33%) lacked diarrhea (atypical presentation), including 2 of 6 (33%)
      with active (untreated) celiac disease and 3 of 9 (33%) with refractory celiac
      disease. Autoimmune disorders were seen in 12 of 19 (63%) patients and
      microscopic colitis (n=7), lymphocytic gastritis (n=2) or collagenous gastritis
      (n=2) were seen in nine patients. Subepithelial collagen thickness was mildly
      (n=6), moderately (n=10), or markedly (n=3) increased and villous atrophy was
      total (n=13) or subtotal (n=6). Phenotypically aberrant intraepithelial
      lymphocytes were not detected in any case. Polymerase chain reaction analysis
      showed a dominant T-cell clone in the only patient with refractory celiac disease
      type II. Histological improvement occurred in 7 of 11 (64%) patients. Overall, 8
      of 19 (42%) responded to gluten-free diet, including 2 of 9 (22%) with refractory
      celiac disease and 10 responded to immunomodulatory therapy, including 6 of 9
      (67%) with refractory celiac disease. Only one patient died from complications of
      refractory celiac disease. No patient developed lymphoma. The vast majority of
      our patients with collagenous sprue had celiac disease. Although, many patients
      required immunomodulatory therapy for symptom control, a subset responded to
      gluten-free diet alone. In our experience, collagenous sprue patients had
      relatively good clinical outcomes.

PMID- 19855377
TI  - Triple-negative breast cancer: clinicopathological characteristics and
      relationship with basal-like breast cancer.
AB  - Triple-negative breast cancer, defined as that with negative expression of
      estrogen and progesterone receptors and cerbB2, accounted for 11% of invasive
      breast cancers in our study, drawn from an original cohort of 7048 women
      diagnosed with breast cancer from the files of the Department of Pathology,
      Singapore General Hospital, over 14 years. Women with triple-negative breast
      cancer were generally postmenopausal, with adverse pathological characteristics
      of high histological grade and frequent nodal metastases. Using a set of 61
      invasive breast cancers earlier profiled into molecular subtypes with expression
      arrays, we defined specificity and sensitivity values for different
      immunohistochemical panels of basal keratins (CK5/6, CK14, CK17, 34 beta E12),
      CD117, EGFR, p63 and SMA in defining basal-like breast cancer. Subsequent
      application of a tri-panel of CK14, EGFR and 34 beta E12 (specificity 100% and
      sensitivity 78%) to our group of 653 triple-negative breast cancers delineated
      84% to be basal-like. Immunohistochemical expression of individual biological
      markers correlated with unfavorable pathological parameters. We conclude that
      triple-negative breast cancers in an Asian population harbor adverse
      pathobiological features, and an immunohistochemical surrogate panel can be
      reliably used to define basal-like cancers among them.

PMID- 19855378
TI  - p53 overexpression in morphologically ambiguous endometrial carcinomas correlates
      with adverse clinical outcomes.
AB  - The distinction between uterine serous and endometrioid carcinomas can usually be
      achieved by morphologic examination alone. However, there are occasional
      'morphologically ambiguous endometrial carcinomas' that show overlapping serous
      and endometrioid features and defy histologic classification. The primary aim of
      this study was to assess the clinical significance of p53 overexpression using
      immunohistochemistry in such tumors. Related aims included (1) assessing
      interobserver diagnostic concordance for histologic subclassification of these
      tumors using a panel of pathologists with and without gynecologic pathology
      expertise and (2) elucidating the histologic features that correlate with p53
      status. Thirty-five such cases were identified during the study period. p53
      overexpression was seen in 17 of 35 cases. Tumors with p53 overexpression were
      associated with a significantly inferior progression-free survival and disease
      specific survival compared with those that lacked p53 overexpression (3-year
      progression-free survival and disease-specific survival were 94 and 100% in
      patients with no p53 overexpression, and 52 and 54% in patients with p53
      overexpression; P=0.02 and 0.003, respectively). The consensus diagnosis rendered
      by gynecologic pathologists was predictive of disease-specific survival
      (P=0.002), but not progression-free survival (P=0.11). Although the interobserver
      diagnostic concordance (kappa=0.70) was substantial for gynecologic pathologists,
      and highly associated with p53 status (77% of 'favor serous' cases showed p53
      overexpression, whereas only 25% of 'favor endometrioid' cases showed p53
      overexpression; P=0.005), the concordance between the consensus diagnosis of the
      two specialized pathologists versus each of three non-specialized pathologists
      was poor (kappa=0.13-0.25). The histologic feature that correlated most with p53
      overexpression was the presence of diffuse high nuclear grade. p53
      immunohistochemistry assays in morphologically ambiguous endometrial carcinomas
      are roughly as clinically informative as gynecologic pathology consultation and
      can be helpful for prognostic assessment and therapeutic decision making in
      difficult endometrial carcinomas.

PMID- 19855379
TI  - Structural basis of abscisic acid signalling.
AB  - The phytohormone abscisic acid (ABA) mediates the adaptation of plants to
      environmental stresses such as drought and regulates developmental signals such
      as seed maturation. Within plants, the PYR/PYL/RCAR family of START proteins
      receives ABA to inhibit the phosphatase activity of the group-A protein
      phosphatases 2C (PP2Cs), which are major negative regulators in ABA signalling.
      Here we present the crystal structures of the ABA receptor PYL1 bound with (+)
      ABA, and the complex formed by the further binding of (+)-ABA-bound PYL1 with the
      PP2C protein ABI1. PYL1 binds (+)-ABA using the START-protein-specific ligand
      binding site, thereby forming a hydrophobic pocket on the surface of the closed
      lid. (+)-ABA-bound PYL1 tightly interacts with a PP2C domain of ABI1 by using the
      hydrophobic pocket to cover the active site of ABI1 like a plug. Our results
      reveal the structural basis of the mechanism of (+)-ABA-dependent inhibition of
      ABI1 by PYL1 in ABA signalling.

PMID- 19855380
TI  - Multiple layers of B cell memory with different effector functions.
AB  - Memory B cells are at the center of longstanding controversies regarding the
      presence of antigen for their survival and their re-engagement in germinal
      centers after secondary challenge. Using a new mouse model of memory B cell
      labeling dependent on the cytidine deaminase AID, we show that after immunization
      with a particulate antigen, B cell memory appeared in several subsets, comprising
      clusters of immunoglobulin M-positive (IgM(+)) and IgG1(+) B cells in germinal
      center-like structures that persisted up to 8 months after immunization, as well
      as IgM(+) and IgG1(+) B cells with a memory phenotype outside of B cell
      follicles. After challenge, the IgG subset differentiated into plasmocytes,
      whereas the IgM subset reinitiated a germinal center reaction. This model, in
      which B cell memory appears in several layers with different functions,
      reconciles previous conflicting propositions.

PMID- 19855381
TI  - Enteric defensins are essential regulators of intestinal microbial ecology.
AB  - Antimicrobial peptides are important effectors of innate immunity throughout the
      plant and animal kingdoms. In the mammalian small intestine, Paneth cell alpha
      defensins are antimicrobial peptides that contribute to host defense against
      enteric pathogens. To determine if alpha-defensins also govern intestinal
      microbial ecology, we analyzed the intestinal microbiota of mice expressing a
      human alpha-defensin gene (DEFA5) and in mice lacking an enzyme required for the
      processing of mouse alpha-defensins. In these complementary models, we detected
      significant alpha-defensin-dependent changes in microbiota composition, but not
      in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking
      losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)
      producing lamina propria T cells. Our data ascribe a new homeostatic role to
      alpha-defensins in regulating the makeup of the commensal microbiota.

PMID- 19855382
TI  - Experimental demonstration of an acoustic magnifying hyperlens.
AB  - Acoustic metamaterials can manipulate sound waves in surprising ways, which
      include collimation, focusing, cloaking, sonic screening and extraordinary
      transmission. Recent theories suggested that imaging below the diffraction limit
      using passive elements can be realized by acoustic superlenses or magnifying
      hyperlenses. These could markedly enhance the capabilities in underwater sonar
      sensing, medical ultrasound imaging and non-destructive materials testing.
      However, these proposed approaches suffer narrow working frequency bands and
      significant resonance-induced loss, which hinders them from successful
      experimental realization. Here, we report the experimental demonstration of an
      acoustic hyperlens that magnifies subwavelength objects by gradually converting
      evanescent components into propagating waves. The fabricated acoustic hyperlens
      relies on straightforward cutoff-free propagation and achieves deep-subwavelength
      resolution with low loss over a broad frequency bandwidth.

PMID- 19855383
TI  - Nanofibrous biologic laminates replicate the form and function of the annulus
      fibrosus.
AB  - Successful engineering of load-bearing tissues requires recapitulation of their
      complex mechanical functions. Given the intimate relationship between function
      and form, biomimetic materials that replicate anatomic form are of great interest
      for tissue engineering applications. However, for complex tissues such as the
      annulus fibrosus, scaffolds have failed to capture their multi-scale structural
      hierarchy. Consequently, engineered tissues have yet to reach functional
      equivalence with their native counterparts. Here, we present a novel strategy for
      annulus fibrosus tissue engineering that replicates this hierarchy with
      anisotropic nanofibrous laminates seeded with mesenchymal stem cells. These
      scaffolds directed the deposition of an organized, collagen-rich extracellular
      matrix that mimicked the angle-ply, multi-lamellar architecture and achieved
      mechanical parity with native tissue after 10 weeks of in vitro culture.
      Furthermore, we identified a novel role for inter-lamellar shearing in
      reinforcing the tensile response of biologic laminates, a mechanism that has not
      previously been considered for these tissues.

PMID- 19855384
TI  - Reduction of the bulk modulus at high pressure in CrN.
AB  - Nitride coatings are increasingly demanded in the cutting- and machining-tool
      industry owing to their hardness, thermal stability and resistance to corrosion.
      These properties derive from strongly covalent bonds; understanding the bonding
      is a requirement for the design of superhard materials with improved
      capabilities. Here, we report a pressure-induced cubic-to-orthorhombic transition
      at approximately 1 GPa in CrN. High-pressure X-ray diffraction and ab initio
      calculations show an unexpected reduction of the bulk modulus, K0, of about 25%
      in the high-pressure (lower volume) phase. Our combined theoretical and
      experimental approach shows that this effect is the result of a large exchange
      striction due to the approach of the localized Cr:t3 electrons to becoming
      molecular-orbital electrons in Cr-Cr bonds. The softening of CrN under pressure
      is a manifestation of a strong competition between different types of chemical
      bond that are found at a crossover from a localized to a molecular-orbital
      electronic transition.

PMID- 19855385
TI  - Porous organic cages.
AB  - Porous materials are important in a wide range of applications including
      molecular separations and catalysis. We demonstrate that covalently bonded
      organic cages can assemble into crystalline microporous materials. The porosity
      is prefabricated and intrinsic to the molecular cage structure, as opposed to
      being formed by non-covalent self-assembly of non-porous sub-units. The three
      dimensional connectivity between the cage windows is controlled by varying the
      chemical functionality such that either non-porous or permanently porous
      assemblies can be produced. Surface areas and gas uptakes for the latter exceed
      comparable molecular solids. One of the cages can be converted by
      recrystallization to produce either porous or non-porous polymorphs with apparent
      Brunauer-Emmett-Teller surface areas of 550 and 23 m2 g(-1), respectively. These
      results suggest design principles for responsive porous organic solids and for
      the modular construction of extended materials from prefabricated molecular
      pores.

PMID- 19855386
TI  - Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by
      toll-like receptor signalling.
AB  - The endoplasmic reticulum (ER) unfolded protein response (UPR) restores
      equilibrium to the ER, but prolonged expression of the UPR effector CHOP
      (GADD153) is cytotoxic. We found that CHOP expression induced by ER stress was
      suppressed by prior engagement of toll-like receptor (TLR) 3 or 4 through a TRIF
      dependent pathway. TLR engagement did not suppress phosphorylation of PERK or eIF
      2alpha, which are upstream of CHOP, but phospho-eIF-2alpha failed to promote
      translation of the CHOP activator ATF4. In mice subjected to systemic ER stress,
      pretreatment with low dose lipopolysaccharide (LPS), a TLR4 ligand, suppressed
      CHOP expression and apoptosis in splenic macrophages, renal tubule cells and
      hepatocytes, and prevented renal dysfunction and hepatosteatosis. This protective
      effect of LPS did not occur in Trif(-/-) mice or in wild-type mice in which CHOP
      expression was genetically restored. Thus, TRIF-mediated signals from TLRs
      selectively attenuate translational activation of ATF4 and its downstream target
      gene CHOP. We speculate that this mechanism evolved to promote survival of TLR
      expressing cells that experience prolonged levels of physiological ER stress in
      the course of the host response to invading pathogens.

PMID- 19855387
TI  - Intraflagellar transport is required for polarized recycling of the TCR/CD3
      complex to the immune synapse.
AB  - Most eukaryotic cells have a primary cilium which functions as a sensory
      organelle. Cilia are assembled by intraflagellar transport (IFT), a process
      mediated by multimeric IFT particles and molecular motors. Here we show that
      lymphoid and myeloid cells, which lack primary cilia, express IFT proteins.
      IFT20, an IFT component essential for ciliary assembly, was found to colocalize
      with both the microtubule organizing centre (MTOC) and Golgi and post-Golgi
      compartments in T-lymphocytes. In antigen-specific conjugates, IFT20 translocated
      to the immune synapse. IFT20 knockdown resulted in impaired T-cell receptor/CD3
      (TCR/CD3) clustering and signalling at the immune synapse, due to defective
      polarized recycling. Moreover, IFT20 was required for the inducible assembly of a
      complex with other IFT components (IFT57 and IFT88) and the TCR. The results
      identify IFT20 as a new regulator of immune synapse assembly in T cells and
      provide the first evidence to implicate IFT in membrane trafficking in cells
      lacking primary cilia, thereby introducing a new perspective on IFT function
      beyond its role in ciliogenesis.

PMID- 19855388
TI  - Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity.
AB  - Slit-Roundabout (Robo) signalling has a well-understood role in axon guidance.
      Unlike in the nervous system, however, Slit-dependent activation of an
      endothelial-specific Robo, Robo4, does not initiate a guidance program. Instead,
      Robo4 maintains the barrier function of the mature vascular network by inhibiting
      neovascular tuft formation and endothelial hyperpermeability induced by pro
      angiogenic factors. In this study, we used cell biological and biochemical
      techniques to elucidate the molecular mechanism underlying the maintenance of
      vascular stability by Robo4. Here, we demonstrate that Robo4 mediates Slit2
      dependent suppression of cellular protrusive activity through direct interaction
      with the intracellular adaptor protein paxillin and its paralogue, Hic-5.
      Formation of a Robo4-paxillin complex at the cell surface blocks activation of
      the small GTPase Arf6 and, consequently, Rac by recruitment of Arf-GAPs (ADP
      ribosylation factor- directed GTPase-activating proteins) such as GIT1.
      Consistent with these in vitro studies, inhibition of Arf6 activity in vivo
      phenocopies Robo4 activation by reducing pathologic angiogenesis in choroidal and
      retinal vascular disease and VEGF-165 (vascular endothelial growth factor-165)
      induced retinal hyperpermeability. These data reveal that a Slit2-Robo4-paxillin
      GIT1 network inhibits the cellular protrusive activity underlying
      neovascularization and vascular leak, and identify a new therapeutic target for
      ameliorating diseases involving the vascular system.

PMID- 19855389
TI  - Frontal eye field neurons signal changes in decision criteria.
AB  - Flexible links between sensory stimuli and behavioral responses underlie many
      cognitive processes. One process that contributes to flexible decision-making is
      categorization. Some categories are innate or overlearned, but, in many cases,
      category boundaries represent flexible decision criteria that can shift on the
      fly to adapt to changes in the environment. The ability to shift category
      boundaries allows decision-making to adapt to changing circumstances. We found
      that monkeys were able to switch rapidly between two category boundaries when
      classifying the speed of a moving dot pattern and that neurons in monkey frontal
      eye field (FEF) changed their activity when the boundary changed. The responses
      of a subpopulation of FEF neurons that were sensitive to both stimulus and
      boundary speed were used to classify the stimuli as accurately as the monkeys'
      performance.

PMID- 19855390
TI  - Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS
      pathways.
AB  - Mammalian sterile 20-like kinase-3b (Mst3b, encoded by Stk24), regulates axon
      outgrowth in embryonic cortical neurons in culture, but its role in vivo and in
      neural repair is unknown. Here we show that Mst3b mediates the axon-promoting
      effects of trophic factors in mature rat retinal ganglion cells (RGCs) and dorsal
      root ganglion (DRG) neurons, and is essential for axon regeneration in vivo.
      Reducing Mst3b levels using short hairpin RNA prevented RGCs and DRG neurons from
      regenerating axons in response to growth factors in culture, as did expression of
      a kinase-dead Mst3b mutant. Conversely, expression of constitutively active Mst3b
      enabled both types of neurons to extend axons without growth factors. In vivo,
      RGCs lacking Mst3b failed to regenerate injured axons when stimulated by
      intraocular inflammation. DRG neurons regenerating axons in vivo showed elevated
      Mst3b activity, and reducing Mst3b expression attenuated regeneration and p42/44
      MAPK activation. Thus, Mst3b regulates axon regeneration in both CNS and PNS
      neurons.

PMID- 19855391
TI  - 'Edgetic' perturbation of a C. elegans BCL2 ortholog.
AB  - Genes and gene products do not function in isolation but within highly
      interconnected 'interactome' networks, modeled as graphs of nodes and edges
      representing macromolecules and interactions between them, respectively. We
      propose to investigate genotype-phenotype associations by methodical use of
      alleles that lack single interactions, while retaining all others, in contrast to
      genetic approaches designed to eliminate gene products completely. We describe an
      integrated strategy based on the reverse yeast two-hybrid system to isolate and
      characterize such edge-specific, or 'edgetic', alleles. We established a proof of
      concept with CED-9, a Caenorhabditis elegans BCL2 ortholog. Using ced-9 edgetic
      alleles, we uncovered a new potential functional link between apoptosis and a
      centrosomal protein. This approach is amenable to higher throughput and is
      particularly applicable to interactome network analysis in organisms for which
      transgenesis is straightforward.

PMID- 19855393
TI  - Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for
      congenital disorders and testicular tumors.
AB  - Genes mutated in congenital malformation syndromes are frequently implicated in
      oncogenesis, but the causative germline and somatic mutations occur in separate
      cells at different times of an organism's life. Here we unify these processes to
      a single cellular event for mutations arising in male germ cells that show a
      paternal age effect. Screening of 30 spermatocytic seminomas for oncogenic
      mutations in 17 genes identified 2 mutations in FGFR3 (both 1948A>G, encoding
      K650E, which causes thanatophoric dysplasia in the germline) and 5 mutations in
      HRAS. Massively parallel sequencing of sperm DNA showed that levels of the FGFR3
      mutation increase with paternal age and that the mutation spectrum at the Lys650
      codon is similar to that observed in bladder cancer. Most spermatocytic seminomas
      show increased immunoreactivity for FGFR3 and/or HRAS. We propose that paternal
      age-effect mutations activate a common 'selfish' pathway supporting proliferation
      in the testis, leading to diverse phenotypes in the next generation including
      fetal lethality, congenital syndromes and cancer predisposition.

PMID- 19855394
TI  - Molecular architecture of the Nup84-Nup145C-Sec13 edge element in the nuclear
      pore complex lattice.
AB  - Nuclear pore complexes (NPCs) facilitate all nucleocytoplasmic transport. These
      massive protein assemblies are modular, with a stable structural scaffold
      supporting more dynamically attached components. The scaffold is made from
      multiple copies of the heptameric Y complex and the heteromeric Nic96 complex. We
      previously showed that members of these core subcomplexes specifically share an
      ACE1 fold with Sec31 of the COPII vesicle coat, and we proposed a lattice model
      for the NPC based on this commonality. Here we present the crystal structure of
      the heterotrimeric 134-kDa complex of Nup84-Nup145C-Sec13 of the Y complex. The
      heterotypic ACE1 interaction of Nup84 and Nup145C is analogous to the homotypic
      ACE1 interaction of Sec31 that forms COPII lattice edge elements and is
      inconsistent with the alternative 'fence-like' NPC model. We construct a
      molecular model of the Y complex and compare the architectural principles of
      COPII and NPC lattices.

PMID- 19855392
TI  - Microduplications of 16p11.2 are associated with schizophrenia.
AB  - Recurrent microdeletions and microduplications of a 600-kb genomic region of
      chromosome 16p11.2 have been implicated in childhood-onset developmental
      disorders. We report the association of 16p11.2 microduplications with
      schizophrenia in two large cohorts. The microduplication was detected in 12/1,906
      (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the
      initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P =
      0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was
      associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in
      the combined sample. A meta-analysis of datasets for multiple psychiatric
      disorders showed a significant association of the microduplication with
      schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P =
      1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with
      autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was
      larger in patients with the microdeletion than in patients with the
      microduplication (P = 0.0007).

PMID- 19855395
TI  - Involvement of a chromatin remodeling complex in damage tolerance during DNA
      replication.
AB  - ATP-dependent chromatin remodeling complexes have been shown to participate in
      DNA replication in addition to transcription and DNA repair. However, the
      mechanisms of their involvement in DNA replication remain unclear. Here, we
      reveal a specific function of the yeast INO80 chromatin remodeling complex in the
      DNA damage tolerance pathways. Whereas INO80 is necessary for the resumption of
      replication at forks stalled by methyl methane sulfonate (MMS), it is not
      required for replication fork collapse after treatment with hydroxyurea (HU).
      Mechanistically, INO80 regulates DNA damage tolerance during replication through
      modulation of PCNA (proliferating cell nuclear antigen) ubiquitination and Rad51
      mediated processing of recombination intermediates at impeded replication forks.
      Our findings establish a mechanistic link between INO80 and DNA damage tolerance
      pathways, indicating that chromatin remodeling is important for accurate DNA
      replication.

PMID- 19855396
TI  - Comprehensive characterization of cytochrome P450 isozyme selectivity across
      chemical libraries.
AB  - The cytochrome P450 (CYP) gene family catalyzes drug metabolism and bioactivation
      and is therefore relevant to drug development. We determined potency values for
      17,143 compounds against five recombinant CYP isozymes (1A2, 2C9, 2C19, 2D6 and
      3A4) using an in vitro bioluminescent assay. The compounds included libraries of
      US Food and Drug Administration (FDA)-approved drugs and screening libraries. We
      observed cross-library isozyme inhibition (30-78%) with important differences
      between libraries. Whereas only 7% of the typical screening library was inactive
      against all five isozymes, 33% of FDA-approved drugs were inactive, reflecting
      the optimized pharmacological properties of the latter. Our results suggest that
      low CYP 2C isozyme activity is a common property of drugs, whereas other
      isozymes, such as CYP 2D6, show little discrimination between drugs and
      unoptimized compounds found in screening libraries. We also identified chemical
      substructures that differentiated between the five isozymes. The pharmacological
      compendium described here should further the understanding of CYP isozymes.

PMID- 19855397
TI  - Extracellular histones are major mediators of death in sepsis.
AB  - Hyperinflammatory responses can lead to a variety of diseases, including sepsis.
      We now report that extracellular histones released in response to inflammatory
      challenge contribute to endothelial dysfunction, organ failure and death during
      sepsis. They can be targeted pharmacologically by antibody to histone or by
      activated protein C (APC). Antibody to histone reduced the mortality of mice in
      lipopolysaccharide (LPS), tumor necrosis factor (TNF) or cecal ligation and
      puncture models of sepsis. Extracellular histones are cytotoxic toward
      endothelium in vitro and are lethal in mice. In vivo, histone administration
      resulted in neutrophil margination, vacuolated endothelium, intra-alveolar
      hemorrhage and macro- and microvascular thrombosis. We detected histone in the
      circulation of baboons challenged with Escherichia coli, and the increase in
      histone levels was accompanied by the onset of renal dysfunction. APC cleaves
      histones and reduces their cytotoxicity. Co-infusion of APC with E. coli in
      baboons or histones in mice prevented lethality. Blockade of protein C activation
      exacerbated sublethal LPS challenge into lethality, which was reversed by
      treatment with antibody to histone. We conclude that extracellular histones are
      potential molecular targets for therapeutics for sepsis and other inflammatory
      diseases.

PMID- 19855398
TI  - Salmonella disrupts lymph node architecture by TLR4-mediated suppression of
      homeostatic chemokines.
AB  - We report that infection of draining lymph nodes (DLNs) by Salmonella typhimurium
      results in the specific downregulation of the homeostatic chemokines CCL21 and
      CXCL13, which are essential for normal DLN organization and function. Our data
      reveal that the mechanism of this suppression is dependent on S. typhimurium LPS
      (sLPS). The decrease in CCL21 expression involves interaction between sLPS and
      CCL21-producing cells within DLNs, triggering a distinct Toll-like receptor 4
      (TLR4)-mediated host signaling response. In this response, suppressor of cytokine
      signaling-3 (Socs3) is upregulated, which negatively regulates mothers against
      decapentaplegic homolog-3 (Smad3)-initiated production of CCL21. Disruption of
      lymph node architecture and cellular trafficking enhances S. typhimurium
      virulence and could represent a mechanism of immune suppression used by pathogens
      that primarily target lymphoid tissue.

PMID- 19855399
TI  - Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic
      replication and reactivation from latency.
AB  - Reversible methylation of histone tails serves as either a positive signal
      recognized by transcriptional assemblies or a negative signal that result in
      repression. Invading viral pathogens that depend upon the host cell's
      transcriptional apparatus are also subject to the regulatory impact of chromatin
      assembly and modifications. Here we show that infection by the alpha
      herpesviruses, herpes simplex virus (HSV) and varicella zoster virus (VZV),
      results in the rapid accumulation of chromatin bearing repressive histone H3 Lys9
      methylation. To enable expression of viral immediate early (IE) genes, both
      viruses use the cellular transcriptional coactivator host cell factor-1 (HCF-1)
      to recruit the lysine-specific demethylase-1 (LSD1) to the viral immediate early
      promoters. Depletion of LSD1 or inhibition of its activity with monoamine oxidase
      inhibitors (MAOIs) results in the accumulation of repressive chromatin and a
      block to viral gene expression. As HCF-1 is a component of the Set1 and MLL1
      histone H3 Lys4 methyltransferase complexes, it thus coordinates modulation of
      repressive H3 Lys9 methylation levels with addition of activating H3 Lys4
      trimethylation marks. Strikingly, MAOIs also block the reactivation of HSV from
      latency in sensory neurons, indicating that the HCF-1 complex is a crucial
      component of the reactivation mechanism. The results support pharmaceutical
      control of histone modifying enzymes as a strategy for controlling herpesvirus
      infections.

PMID- 19855400
TI  - Notch3 signaling promotes the development of pulmonary arterial hypertension.
AB  - Notch receptor signaling is implicated in controlling smooth muscle cell
      proliferation and in maintaining smooth muscle cells in an undifferentiated
      state. Pulmonary arterial hypertension is characterized by excessive vascular
      resistance, smooth muscle cell proliferation in small pulmonary arteries, leading
      to elevation of pulmonary vascular resistance, right ventricular failure and
      death. Here we show that human pulmonary hypertension is characterized by
      overexpression of NOTCH3 in small pulmonary artery smooth muscle cells and that
      the severity of disease in humans and rodents correlates with the amount of
      NOTCH3 protein in the lung. We further show that mice with homozygous deletion of
      Notch3 do not develop pulmonary hypertension in response to hypoxic stimulation
      and that pulmonary hypertension can be successfully treated in mice by
      administration of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl
      ester (DAPT), a gamma-secretase inhibitor that blocks activation of Notch3 in
      smooth muscle cells. We show a mechanistic link from NOTCH3 receptor signaling
      through the Hairy and enhancer of Split-5 (HES-5) protein to smooth muscle cell
      proliferation and a shift to an undifferentiated smooth muscle cell phenotype.
      These results suggest that the NOTCH3-HES-5 signaling pathway is crucial for the
      development of pulmonary arterial hypertension and provide a target pathway for
      therapeutic intervention.

PMID- 19855401
TI  - The spectrum of latent tuberculosis: rethinking the biology and intervention
      strategies.
AB  - Immunological tests provide evidence of latent tuberculosis in one third of the
      global population, which corresponds to more than two billion individuals. Latent
      tuberculosis is defined by the absence of clinical symptoms but carries a risk of
      subsequent progression to clinical disease, particularly in the context of co
      infection with HIV. In this Review we discuss the biology of latent tuberculosis
      as part of a broad range of responses that occur following infection with
      Mycobacterium tuberculosis, which result in the formation of physiologically
      distinct granulomatous lesions that provide microenvironments with differential
      ability to support or suppress the persistence of viable bacteria. We then show
      how this model can be used to develop a rational programme to discover effective
      drugs for the eradication of M. tuberculosis infection.

PMID- 19855402
TI  - New insights into the differentiation and function of T follicular helper cells.
AB  - The seminal studies characterizing T follicular helper (T(FH)) cells described a
      non-polarized CD4(+) T cell population with a unique ability to home to B cell
      follicles and to induce antibody production by B cells. In the past few years,
      the study of T(FH) cells has enjoyed a renaissance and there has been a surge of
      research activity aimed at understanding the function and differentiation of
      these important cells. This Review focuses on the current progress in T(FH) cell
      biology and the important questions that remain unanswered. Particular attention
      is paid to recent studies that support the idea that T(FH) cells are a separate T
      cell lineage and those that probe the relationship of T(FH) cells to other T
      helper cell subsets.

PMID- 19855403
TI  - The follicular versus marginal zone B lymphocyte cell fate decision.
AB  - Bone marrow-derived B cells make an important cell fate choice to develop into
      either follicular B cells or marginal zone B cells in the spleen, which depends
      on signalling through the B cell receptor, Notch2, the receptor for B cell
      activating factor and the canonical nuclear factor-kappaB pathway, as well as
      signals involved in the migration and anatomical retention of marginal zone B
      cells. Recent information discussed in this Review reconciles some of the
      controversies regarding the role of the B cell receptor in this cell fate
      decision and a clearer picture has also emerged regarding the anatomical location
      of ligands for Notch2 in the spleen. This cell fate decision could provide
      mechanistic insights that are relevant to other commitment events in lymphocytes.

PMID- 19855406
TI  - Obesity 2009. Abstracts of the 27th Annual Scientific Meeting of The Obesity
      Society, October 24-28, 2009, Washington, DC, USA.

PMID- 19855404
TI  - Regulation of tissue homeostasis by NF-kappaB signalling: implications for
      inflammatory diseases.
AB  - The nuclear factor-kappaB (NF-kappaB) signalling pathway regulates immune
      responses and is implicated in the pathogenesis of many inflammatory diseases.
      Given the well established pro-inflammatory functions of NF-kappaB, inhibition of
      this pathway would be expected to have anti-inflammatory effects. However, recent
      studies in mouse models have led to surprising and provocative results, as NF
      kappaB inhibition in epithelial cells resulted in the spontaneous development of
      severe chronic inflammatory conditions. These findings indicate that NF-kappaB
      signalling acts in non-immune cells to control the maintenance of tissue immune
      homeostasis. This Review discusses the mechanisms by which NF-kappaB activity in
      non-immune cells regulates tissue immune homeostasis and prevents the
      pathogenesis of inflammatory diseases.

PMID- 19855419
TI  - The price of a kidney.

PMID- 19855405
TI  - Intestinal mucosal barrier function in health and disease.
AB  - Mucosal surfaces are lined by epithelial cells. These cells establish a barrier
      between sometimes hostile external environments and the internal milieu. However,
      mucosae are also responsible for nutrient absorption and waste secretion, which
      require a selectively permeable barrier. These functions place the mucosal
      epithelium at the centre of interactions between the mucosal immune system and
      luminal contents, including dietary antigens and microbial products. Recent
      advances have uncovered mechanisms by which the intestinal mucosal barrier is
      regulated in response to physiological and immunological stimuli. Here I discuss
      these discoveries along with evidence that this regulation shapes mucosal immune
      responses in the gut and, when dysfunctional, may contribute to disease.

PMID- 19855420
TI  - Transplantation: time to rethink immunosuppression by mTOR inhibitors?
AB  - Several surprising findings indicate that pharmacological blocking of the
      multifunctional enzyme mTor fosters distinct differentiation programs in
      different immunocompetent cells. These data might lead to a striking change in
      our view of the role that mTor inhibition should have in immunosuppressive
      therapy for allogeneic transplant recipients.

PMID- 19855421
TI  - Glomerular disease: sugars and immune complex formation in IgA nephropathy.
AB  - In vitro evidence suggests that immune complex formation in IgA nephropathy is
      determined by the sugar content of the IgA1 hinge region. Absence of galactose
      residues in this region renders the IgA1 molecule immunogenic.

PMID- 19855422
TI  - Transplantation: Supplemental vitamin D: will do no harm and might do good.
AB  - Vitamin D insufficiency is endemic amongst renal transplant recipients,as it is
      in other individuals with chronic diseases, both within and beyond nephrology.
      Few data exist to guide vitamin D replacement strategies,but indirect evidence
      points to likely skeletal, and possibly extraskeletal, benefits from
      supplementation.

PMID- 19855423
TI  - Dialysis: Intradermal HBV vaccination is preferable in non-responders.
AB  - In patients on hemodialysis with a history of failure to respond to hepatitis B
      vaccination, intradermal revaccination is more effective than repeat
      intramuscular vaccination. Intradermal vaccine administration might become the
      standard of care for high-risk patients.

PMID- 19855424
TI  - Nephrotic syndrome: a watershed in the understanding of membranous nephropathy.
AB  - Proof has at last been provided that idiopathic membranous nephropathy is caused
      by autoantibodies to proteins expressed by podocytes. The discovery that
      autoantibodies to the M-type secretory phospholipase A2 receptor were present in
      most individuals affected by the condition opens a new era for the management of
      membranous nephropathy.

PMID- 19855425
TI  - Transplantation: Personalizing induction therapy in kidney transplantation.
AB  - Induction therapy with rabbit anti-thymocyte globulin is preferable to induction
      with daclizumab in renal transplant recipients at high immunological risk. These
      findings provide additional support to the idea that personalized
      immunosuppressive regimens should be developed in renal transplant recipients.

PMID- 19855426
TI  - Angiogenic factor abnormalities and fetal demise in a twin pregnancy.
AB  - BACKGROUND: An otherwise healthy 31-year-old gravida 2 para 1 woman with a
      spontaneous dichorionic, diamniotic twin pregnancy presented with hypertension,
      nephrotic syndrome and renal insufficiency at 19 weeks' gestation. Fetal
      ultrasound revealed severe intrauterine growth restriction of one fetus and
      measurement of serum anti-angiogenic and angiogenic factors were consistent with
      a profound anti-angiogenic state. After one fetus died and the placenta became
      increasingly echogenic, the patient improved clinically, and weekly ultrasound
      assessments of the intact co-twin from 22 weeks onwards demonstrated symmetrical
      fetal growth along the 10th centile. Repeat serum angiogenic factors at 24 weeks'
      gestation revealed considerable improvement of the anti-angiogenic state and
      paralleled resolution of the clinical syndrome. INVESTIGATIONS: Physical
      examination, laboratory evaluations including full blood count, liver function
      tests, electrolytes, renal function tests, screening for glomerular-based
      disease, 24-h urine collection for total protein, analysis of serum anti
      angiogenic and angiogenic factors, fetal ultrasonography and placental Doppler
      examination. DIAGNOSIS: Spontaneous resolution of early-onset pre-eclampsia after
      single fetal demise in a twin pregnancy. MANAGEMENT: Labetalol was given to treat
      hypertension and furosemide was given as needed for edema. The patient was
      closely followed up throughout pregnancy in a combined nephrology/obstetrics
      outpatient clinic.

PMID- 19855428
TI  - Silencing of the Lats2 tumor suppressor overrides a p53-dependent oncogenic
      stress checkpoint and enables mutant H-Ras-driven cell transformation.
AB  - The Lats2 tumor suppressor protein has been implicated earlier in promoting p53
      activation in response to mitotic apparatus stress, by preventing Mdm2-driven p53
      degradation. We now report that Lats2 also has a role in an ATR-Chk1-mediated
      stress check point in response to oncogenic H-Ras. Activated mutant H-Ras
      triggers the translocation of Lats2 from centrosomes into the nucleus, coupled
      with an increase in Lats2 protein levels. This leads to the induction of p53
      activity, upregulation of proapoptotic genes, downregulation of antiapoptotic
      genes and eventually apoptotic cell death. Many of the cells that survive
      apoptosis undergo senescence. However, a fraction of the cells escape this
      checkpoint mechanism, despite maintaining a high mutant H-Ras expression. These
      escapers display increased genome instability, as evidenced by a substantial
      fraction of cells with micronuclei and cells with polyploid genomes.
      Interestingly, such cells show markedly reduced levels of Lats2, in conjunction
      with enhanced hypermethylation of the Lats2 gene promoter. Our findings suggest
      that Lats2 might have an important role in quenching H-Ras-induced
      transformation, whereas silencing of Lats2 expression might serve as a mechanism
      to enable tumor progression.

PMID- 19855427
TI  - Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of
      FOXP3+ regulatory T cells.
AB  - Classical zinc-dependent histone deacetylases (HDACs) catalyse the removal of
      acetyl groups from histone tails and also from many non-histone proteins,
      including the transcription factor FOXP3, a key regulator of the development and
      function of regulatory T cells. Many HDAC inhibitors are in cancer clinical
      trials, but a subset of HDAC inhibitors has important anti-inflammatory or
      immunosuppressive effects that might be of therapeutic benefit in immuno
      inflammatory disorders or post-transplantation. At least some of these effects
      result from the ability of HDAC inhibitors to enhance the production and
      suppressive functions of FOXP3(+) regulatory T cells. Understanding which HDACs
      contribute to the regulation of the functions of regulatory T cells may further
      stimulate the development of new class- or subclass-specific HDAC inhibitors with
      applications beyond oncology.

PMID- 19855429
TI  - Serum protein signature may improve detection of ductal carcinoma in situ of the
      breast.
AB  - Ductal carcinoma in situ (DCIS) of the breast is part of a spectrum of
      preinvasive lesions that originate within normal breast tissue and progress to
      invasive breast cancer. The detection of DCIS is important for the reduction of
      mortality from breast cancer, but the diagnosis of preinvasive breast tumors is
      hampered by the lack of an adequate detection method. To identify the changes in
      protein expression during the initial stage of tumorigenesis and to identify the
      presence of new DCIS markers, we analysed serum from 60 patients with breast
      cancer and 60 normal controls using mass spectrometry. A 23-protein index was
      generated that correctly distinguishes the DCIS and control groups with
      sensitivities and specificities in excess of 80% in two independent cohorts. Two
      candidate peptides were purified and identified as platelet factor 4 (PF-4) and
      complement C3a(desArg) anaphylatoxin (C3a(desArg)) using liquid chromatography
      tandem mass spectrometry (LC-MS/MS). In an independent serum set of 165 patients,
      PF-4 and C3a(desArg) were significantly upregulated in DCIS compared with non
      cancerous controls, as validated using western blot and enzyme-linked
      immunosorbent assay. We conclude that our serum protein-based test, used in
      conjunction with image-based screening practices, could improve the sensitivity
      and specificity of breast cancer detection.

PMID- 19855430
TI  - Histone deacetylases and the immunological network: implications in cancer and
      inflammation.
AB  - The initiation, magnitude and duration of an immune response against antigens are
      a tightly regulated process involving a dynamic, orchestrated balance of pro- and
      anti-inflammatory pathways in immune cells. Such a delicate balance is critical
      for allowing efficient immune response against foreign antigens while preventing
      autoimmune attack against self-antigens. In recent years, much effort has been
      devoted to understanding immune evasion by cancer cells. Also, significant
      advances have been made in mechanistically understanding the role of pro- and
      anti-inflammatory cytokines in the regulation of immune responses against
      antigens, including those expressed by tumors. However, we still know very little
      about the regulation of inflammatory/anti-inflammatory genes in their natural
      setting, the chromatin substrate. Several mechanisms have been identified to
      influence chromatin flexibility and allow dynamic changes in gene expression.
      Among those, chromatin modifications induced by acetylation and deacetylation of
      histone tails have gained wide attention. In this study, we discuss the role of
      histone deacetylases in the transcriptional regulation of genes involved in the
      inflammatory response and how these enzymes coordinate the dynamic expression of
      these genes during an immune response. This emerging knowledge is opening new
      avenues to better understand epigenetic regulation of inflammatory responses and
      providing new molecular targets for either amplifying or ameliorating immune
      responses.

PMID- 19855431
TI  - Selective inhibition of choline kinase simultaneously attenuates MAPK and
      PI3K/AKT signaling.
AB  - Choline is an essential anabolic substrate for the synthesis of phospholipids.
      Choline kinase phosphorylates choline to phosphocholine that serves as a
      precursor for the production of phosphatidylcholine, the major phospholipid
      constituent of membranes and substrate for the synthesis of lipid signaling
      molecules. Nuclear magnetic resonance (NMR)-based metabolomic studies of human
      tumors have identified a marked increase in the intracellular concentration of
      phosphocholine relative to normal tissues. We postulated that the observed
      intracellular pooling of phosphocholine may be required to sustain the production
      of the pleiotropic lipid second messenger, phosphatidic acid. Phosphatidic acid
      is generated from the cleavage of phosphatidylcholine by phospholipase D2 and is
      a key activator of the mitogen-activated protein kinase (MAPK) and
      phosphatidylinositol 3-kinase (PI3K)/AKT survival signaling pathways. In this
      study we show that the steady-state concentration of phosphocholine is increased
      by the ectopic expression of oncogenic H-Ras(V12) in immortalized human bronchial
      epithelial cells. We then find that small interfering RNA (siRNA) silencing of
      choline kinase expression in transformed HeLa cells completely abrogates the high
      concentration of phosphocholine, which in turn decreases phosphatidylcholine,
      phosphatidic acid and signaling through the MAPK and PI3K/AKT pathways. This
      simultaneous reduction in survival signaling markedly decreases the anchorage
      independent survival of HeLa cells in soft agar and in athymic mice. Last, we
      confirm the relative importance of phosphatidic acid for this pro-survival effect
      as phosphatidic acid supplementation fully restores MAPK signaling and partially
      rescues HeLa cells from choline kinase inhibition. Taken together, these data
      indicate that the pooling of phosphocholine in cancer cells may be required to
      provide a ready supply of phosphatidic acid necessary for the feed-forward
      amplification of cancer survival signaling pathways.

PMID- 19855432
TI  - Prevention of premature senescence requires JNK regulation of Bcl-2 and reactive
      oxygen species.
AB  - Premature senescence is considered as a cellular defense mechanism to prevent
      tumorigenesis. Although recent evidences show that c-Jun N-terminal kinase (JNK)
      is involved in the senescence process, the mechanism for this regulation is not
      fully understood. Here, we examined the role of JNK in premature senescence of
      tumor cells. Treatment of cells with the JNK-specific inhibitor SP600125 caused
      phenotypical changes of senescence and triggered a rapid increase in
      mitochondrial reactive oxygen species (ROS) production and DNA-damage response
      (DDR) in MCF7 breast carcinoma cells. ROS generation was attributed to the
      suppression of B-cell lymphoma-2 (Bcl-2) phosphorylation, and resulted in DNA
      damage and p53 activation. Bax did not change their localization to the
      mitochondria, which is required for apoptosis. The essential roles of JNK and
      phosphorylated Bcl-2 in preventing premature senescence were confirmed using RNA
      interference and ectopic expression of mutants of Bcl-2, including phosphomimetic
      and nonphosphorylatable forms. These findings were evidenced in H460 lung
      carcinoma cells and primary human embryonic fibroblasts. Altogether, our results
      showed that loss of JNK activity triggers a Bcl-2/ROS/DDR signaling cascade that
      ultimately leads to premature senescence, indicating that basal JNK activity is
      essential in preventing premature senescence.

PMID- 19855433
TI  - Activated BRAF induces gliomas in mice when combined with Ink4a/Arf loss or Akt
      activation.
AB  - Mutations in receptor tyrosine kinase (RTK) growth factor receptors (epidermal
      growth factor receptor, platelet-derived growth factor receptor, MET and ERBB2),
      which result in downstream activation of the RAS/RAF/MEK/ERK mitogen-activated
      protein kinase (MAPK) pathway and PI(3)K/Akt pathway, are found in almost all
      high-grade gliomas and MAPK signaling is necessary for continued glioma
      maintenance. In addition, BRAF is mutated in the majority of low-grade gliomas
      and its expression and activity is significantly increased in the majority of
      high-grade gliomas. Although the importance of RTKs and RAS signaling in glioma
      development has been shown, the role of BRAF has yet to be characterized. We
      evaluated the effect of activated BRAF in glioma formation using the retroviral
      replication-competent avian leukosis virus long terminal repeat, splice acceptor
      (RCAS)/TVA system to transfer genes encoding activated forms of BRAF, KRas, Akt
      and Cre to nestin-expressing neural progenitor cells in Ink4a/Arf(lox/lox) mice
      in vivo. Although expression of activated BRAF alone is not sufficient for
      tumorigenesis, the combination of activated BRAF and Akt or BRAF with Ink4a/Arf
      loss is transforming. Interestingly, activated BRAF generates gliomas with
      characteristics similar to activated KRas in the context of Akt but not Ink4a/Arf
      loss. Our studies show a role for BRAF activation and signaling in glioma
      development and as potential target for glioma therapy.

PMID- 19855434
TI  - Inhibitors of HSP90 block p95-HER2 signaling in Trastuzumab-resistant tumors and
      suppress their growth.
AB  - The anti-HER2 antibody Trastuzumab (Herceptin) has been proven to be effective in
      the treatment of HER2-overexpressing breast cancer; resistance, however,
      invariably emerges in metastatic tumors. The expression of p95-HER2, a form of
      HER2 with a truncated extracellular domain that lacks the Trastuzumab binding
      epitope, has been implicated as a mechanism of resistance to the antibody. We
      utilized an in vivo tumor model that overexpresses p95-HER2 and showed it to be
      resistant to the signaling and antitumor effects of Trastuzumab. We find that
      both full-length and p95-HER2 interact with the HSP90 chaperone protein and are
      degraded in tumor cells exposed to HSP90 inhibitors in tissue culture and in
      vivo. Loss of expression of p95-HER2 is accompanied by downregulation of the
      phosphoinositide-3 kinase/AKT and extracellular signal-regulated kinase signaling
      pathways and inhibition of cell proliferation. Chronic administration of HSP90
      inhibitors in vivo results in sustained loss of HER2 and p95-HER2 expression and
      inhibition of AKT activation, together with induction of apoptosis and complete
      inhibition of tumor growth in Trastuzumab-resistant, p95-HER2-overexpressing
      models. Thus, p95-HER2 is an HSP90 client protein, the expression and function of
      which can be effectively suppressed in vivo by HSP90 inhibitors. HSP90 inhibition
      is therefore a potentially effective therapeutic strategy for p95-HER2-mediated
      Trastuzumab-resistant breast cancer.

PMID- 19855435
TI  - Overexpression of myosin VI in prostate cancer cells enhances PSA and VEGF
      secretion, but has no effect on endocytosis.
AB  - Tissue expression microarrays, employed to determine the players and mechanisms
      leading to prostate cancer development, have consistently shown that myosin VI, a
      unique actin-based motor, is upregulated in medium-grade human prostate cancers.
      Thus, to understand the role of myosin VI in prostate cancer development, we have
      characterized its intracellular localization and function in the prostate cancer
      cell line LNCaP. Using light and electron microscopy, we identified myosin VI on
      Rab5-positive early endosomes, as well as on recycling endosomes and the trans
      Golgi network. Intracellular targeting seems to involve two myosin VI-interacting
      proteins, GIPC and LMTK2, both of which can be co-immunoprecipitated with myosin
      VI from LNCaP cells. The absence of Disabled-2 (Dab2), a tumour suppressor and
      myosin VI-binding partner, inhibits recruitment of myosin VI to endocytic
      structures at the plasma membrane in LNCaP cells, but interestingly has no effect
      on endocytosis. Small interfering RNA-mediated downregulation of myosin VI
      expression results in a significant reduction in prostate-specific antigen (PSA)
      and vascular endothelial growth factor (VEGF) secretion in LNCaP cells. Our
      results suggest that in prostate cancer cells, myosin VI regulates protein
      secretion, but the overexpression of myosin VI has no major impact on clathrin
      mediated endocytosis.

PMID- 19855437
TI  - Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative
      breast cancer cells by modulating the EGFR/HER-2 pathway.
AB  - Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is an ingredient of chili
      peppers with inhibitory effects against cancer cells of different origin. We
      examined the activity of capsaicin on breast cancer cells in vitro and in vivo.
      The drug potently inhibited growth of ER-positive (MCF-7, T47D, BT-474) and ER
      negative (SKBR-3, MDA-MB231) breast cancer cell lines, which was associated with
      G(0)/G(1) cell-cycle arrest, increased levels of apoptosis and reduced protein
      expression of human epidermal growth factor receptor (EGFR), HER-2, activated
      extracellular-regulated kinase (ERK) and cyclin D1. In contrast, cell-cycle
      regulator p27(KIP1), caspase activity as well as poly-ADP ribose polymerase
      (PARP) cleavage were increased. Notably, capsaicin blocked breast cancer cell
      migration in vitro and decreased by 50% the size of MDA-MB231 breast cancer
      tumors growing orthotopically in immunodeficient mice without noticeable drug
      side effects. in vivo activation of ERK was clearly decreased, as well as
      expression of HER-2 and cyclin D1, whereas caspase activity and PARP cleavage
      products were increased in tumors of drug-treated mice. Besides, capsaicin
      potently inhibited the development of pre-neoplastic breast lesions by up to 80%
      without evidence of toxicity. Our data indicate that capsaicin is a novel
      modulator of the EGFR/HER-2 pathway in both ER-positive and -negative breast
      cancer cells with a potential role in the treatment and prevention of human
      breast cancer.

PMID- 19855439
TI  - Management of relapse after allo-SCT for AML and the role of second
      transplantation.
AB  - Relapse after allo-SCT for AML carries very poor prognosis. Second allo-SCT,
      although curative, is not an appropriate treatment option for a large number of
      relapsing patients (only 2-20% patients receive a second allo-SCT), and efforts
      to increase the number of patients who may benefit from a second allo-SCT are
      ongoing. In addition, understanding the varied biological processes that are
      operative in disease relapse has encouraged the development of novel therapies,
      and could be beneficial to patients who are currently managed conservatively with
      supportive care for relapsed disease. Incorporating novel combinations of drugs
      with immunomodulation, although theoretically attractive, should be tested in the
      setting of clinical trials. In this review, we discuss the currently available
      approaches for relapsed AML after allo-SCT.

PMID- 19855438
TI  - Status of minimal residual disease determines outcome of autologous hematopoietic
      SCT in adult ALL.
AB  - The role of autologous hematopoietic SCT (autoHSCT) in the treatment of high-risk
      (HR) adult ALL is controversial. In this study, we retrospectively analyzed the
      results of autoHSCT according to the status of minimal residual disease (MRD) at
      transplantation, as a joint analysis of the European Study Group for Adult ALL
      (EWALL). Data on 123 recipients of autoHSCT, aged 31 (16-59) years, with B
      lineage (n=77) or T-lineage (n=46) ALL were included. In a cohort of Ph-negative
      ALL, the probability of leukemia-free survival at 5 years was higher for patients
      with MRD <0.1% compared with those with MRD > or = 0.1% (57 vs 17%, P=0.0002).
      The difference was significant for T-lineage ALL (62 vs 8%, P=0.001), and a
      tendency was observed for B-lineage ALL (54 vs 26%, P=0.17). In a multivariate
      analysis, adjusted for other potential prognostic factors, high MRD level
      remained the only independent factor associated with increased risk of failure
      (risk ratio, 2.8; P=0.0005). We conclude that MRD determines the outcome of
      autoHSCT in HR adult ALL. Our results suggest the need to reevaluate the role of
      this treatment option in prospective trials.

PMID- 19855436
TI  - Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis.
AB  - Heparan sulfate (HS) proteoglycans (HSPGs) bind to multiple growth
      factors/morphogens and regulate their signaling. 6-O-sulfation (6S) of
      glucosamine within HS chains is critical for many of these ligand interactions.
      Sulf-1 and Sulf-2, which are extracellular neutral-pH sulfatases, provide a novel
      post-synthetic mechanism for regulation of HSPG function by removing 6S from
      intact HS chains. The Sulfs can thereby modulate several signaling pathways,
      including the promotion of Wnt signaling. We found induction of SULF2 transcripts
      and Sulf-2 protein in human lung adenocarcinoma and squamous cell carcinoma, the
      two major classes of non-small-cell lung carcinomas (NSCLCs). We confirmed
      widespread Sulf-2 protein expression in tumor cells of 10/10 surgical specimens
      of human lung squamous carcinomas. We studied five Sulf-2(+) NSCLC cell lines,
      including two, which were derived by cigarette-smoke transformation of bronchial
      epithelial cells. shRNA-mediated Sulf-2 knockdown in these lines caused an
      increase in 6S on their cell surface and in parallel reversed their transformed
      phenotype in vitro, eliminated autocrine Wnt signaling and strongly blunted
      xenograft tumor formation in nude mice. Conversely, forced Sulf-2 expression in
      non-malignant bronchial epithelial cells produced a partially transformed
      phenotype. Our findings support an essential role for Sulf-2 in lung cancer, the
      leading cancer killer.

PMID- 19855440
TI  - Achievement of complete donor-type chimerism and remission with dasatinib in
      Philadelphia chromosome-positive ALL relapsing after allogeneic transplantation.

PMID- 19855441
TI  - Autologous haematopoietic stem cell transplantation for secondary progressive
      multiple sclerosis: an exploratory cost-effectiveness analysis.
AB  - Treatment options for secondary progressive multiple sclerosis (SPMS) are
      limited. Mitoxantrone is routinely used to stabilize disease progression;
      however, evolving evidence suggests clinical benefit from intensive treatment
      with autologous haematopoietic stem cell transplantation (HSCT). Given
      differences in cost and outcomes, preliminary cost-effectiveness studies are
      warranted if this approach is to be developed for more widespread application in
      SPMS. We developed a decision-analytic Markov model to explore the potential cost
      effectiveness of autologous HSCT versus mitoxantrone in SPMS, using patient-level
      data from registry sources. The model evaluates the lifetime costs and health
      outcomes associated with disability progression and relapse. Sensitivity analyses
      were undertaken to examine the uncertainty surrounding cost-effectiveness
      outcomes. In the absence of randomised controlled trial (RCT) evidence,
      conditions for comparative analysis were not ideal. Under optimistic assumptions,
      HSCT is estimated to cost below pound3000 per quality adjusted life year gained.
      However, when a strict 6-month sustained progression rule is adopted, HSCT may be
      less effective and more expensive than mitoxantrone. The model results were
      sensitive to reducing procedural costs and HSCT-related mortality. We conclude
      that HSCT could potentially achieve an acceptable level of cost-effectiveness.
      However, caution should be exercised as large, high-quality RCTs comparing HSCT
      versus mitoxantrone are necessary to validate these findings.

PMID- 19855443
TI  - [Out of Norway to be better].

PMID- 19855442
TI  - Viral-load and B-lymphocyte monitoring of EBV reactivation after allogeneic
      hemopoietic SCT in children.
AB  - EBV-associated post transplant lymphoproliferative disease (EBV-PTLD) is a life
      threatening complication that may occur after hemopoietic SCT. We prospectively
      screened 80 children on a weekly basis using nested quantitative PCR to evaluate
      EBV genome copies. EBV viral load <1000 copies per 10(5) PBMC was observed in 63%
      of transplants, whereas it was between 1000 and 9999 copies per 10(5) PBMC in
      13%, and between 10 000 and 19 999 in 10%, with no significant increase in
      percentage of CD20+ lymphocytes. Viral load reached > or = 20 000 copies per
      10(5) PBMC in 14% of patients, and rituximab was administered to 75% of them.
      None of the patients except one developed a lymphoproliferative disease. Our
      study found that only 13% of unrelated donor HSCT recipients had a very high risk
      of EBV-PTLD defined as > or = 20 000 geq per 10(5) PBMC associated with an
      increase in CD20+ lymphocyte. We suggest that rituximab could be administered in
      the presence of very high levels of EBV-DNA viral load or in the presence of mid
      levels of EBV-DNA viral load associated with an increase in the percentage of
      CD20+ lymphocytes. Through this approach, we significantly reduced the number of
      patients treated with rituximab, and consequently the acute and chronic adverse
      events related to this treatment.

PMID- 19855444
TI  - [Norwegian vascular surgery in "the year of vascular surgery"].

PMID- 19855445
TI  - [The problematic difference].

PMID- 19855446
TI  - [Prevalence of home ventilation therapy in Norway].

PMID- 19855447
TI  - [Complications after gastrointestinal surgery].

PMID- 19855448
TI  - [Genetics in chronic obstructive pulmonary disease].

PMID- 19855449
TI  - [Use of omega-3 fatty acids in the prevention of heart disease].

PMID- 19855450
TI  - [Borrelia burgdorferi--a unique bacterium].

PMID- 19855451
TI  - [A patient with aortic stenosis and reduced left ventricular function].

PMID- 19855452
TI  - [A diagnosis which requires biopsy].

PMID- 19855453
TI  - [Epidemiology, investigation and treatment indication in aortic aneurysm].

PMID- 19855454
TI  - [Thoracic abdominal aneurysms--open surgery and endovascular treatment].

PMID- 19855455
TI  - [Laboratory diagnosis of Lyme borreliosis].

PMID- 19855456
TI  - [Help, I'm still family practitioner!].

PMID- 19855457
TI  - [Borrelia--serologic tests for benefit and problems].

PMID- 19855458
TI  - [We have taken the challenge].

PMID- 19855459
TI  - [Legal equality or tombola?].

PMID- 19855460
TI  - [Narratives about cancer--the meeting with health care].

PMID- 19855461
TI  - [Demographic changes in developing countries].

PMID- 19855462
TI  - [Protein rich ready-to-use food to undernourished children].

PMID- 19855463
TI  - Second-harmonic generation of a 1560-nm distributed-feedback laser by use of a
      KNbO(3) crystal for frequency locking to the (87)Rb D(2) line at 780 nm.
AB  - Second-harmonic generation of a semiconductor distributed-feedback laser at 1560
      nm is described. It is produced by use of a 4.8-mm-long KNbO(3) crystal at room
      temperature. As much as 2.2 nW of power at 780 nm is obtained for 11.3 mW of
      fundamental power incident upon the crystal. This signal is used to interrogate a
      component of the linear absorption profile of the D(2) line in (87)Rb (780.241
      nm) and to produce an error signal used to frequency lock the 1560-nm distributed
      feedback laser. Such a system can therefore be a candidate for establishing an
      absolute wavelength standard at 1560 nm.

PMID- 19855464
TI  - Modulational instability of continuous waves and one-dimensional temporal
      solitons in fiber arrays.
AB  - We present a linear stability analysis of two-dimensional continuous waves and
      one-dimensional temporal solitons in nonlinear-optical fiber arrays. Guided by
      this analysis, we use numerical integrations of the governing equations to show
      that these arrays are all-optical switching devices. Light injected into the N
      fiber array is temporally compressed and spatially localized into a few fibers on
      output.

PMID- 19855465
TI  - Arrangement of fiber pieces for a wide wavelength conversion range by fiber four
      wave mixing.
AB  - A new technique is reported for obtaining a wide wavelength conversion range in
      fiber four-wave mixing. One fiber is cut into short fiber pieces and rearranged,
      considering the zero-dispersion wavelength of each fiber piece. With this
      rearrangement, the wavelength conversion range is expanded, compared with that in
      the original fiber. An experiment using a 6-km fiber confirms the technique.

PMID- 19855466
TI  - Intersubband-transition-induced phase matching.
AB  - We suggest the use of the refractive-index changes associated with the
      intersubband transitions in quantum wells for phase matching in nonlinear
      materials. An improvement in the conversion efficiency of mid-IR second-harmonic
      generation by almost 2 orders of magnitude over non-phase-matched bulk GaAs is
      predicted. We also show that the linear phase contributions of intersubband
      transitions used for resonant enhancement of second-harmonic generation must be
      considered, as they could limit the conversion efficiency by increasing the phase
      mismatch on one hand or offset the bulk's dispersion and lead to phase matching
      on the other.

PMID- 19855467
TI  - Dimensionality and size of photorefractive spatial solitons.
AB  - We study experimentally self-trapping of optical beams in photorefractive media
      and show that the trapping is inherently asymmetric with respect to the two
      (transverse) trapping dimensions. We also present experimental results that show
      how the sizes of the resultant photorefractive spatial solitons are independent
      (within their range of existence) of the amplitude of the externally applied
      electric field used to generate them.

PMID- 19855468
TI  - Nonlinear compensation of chromatic dispersion for phase- and intensity-modulated
      signals in the presence of amplified spontaneous emission noise.
AB  - We numerically study the evolution of nonsoliton signals in fiber links in the
      presence of the Kerr effect, chromatic dispersion, and the amplified spontaneous
      emission of optical amplifiers. Conditions in which the amplified spontaneous
      emission noise does not deeply affect the signal propagation are found, and the
      nonlinear Kerr compensation of the distortion induced by the chromatic dispersion
      is shown.

PMID- 19855469
TI  - High-power amplification of femtosecond optical pulses in a diode-pumped fiber
      system.
AB  - We report a compact all-diode-laser-pumped erbium-doped fiber system consisting
      of an environmentally stable Kerr-type mode-locked fiber oscillator and a fiber
      amplifier. High-repetition-rate (38 MHz) 200-fs-duration pulses were amplified to
      as much as 3 nJ of energy and 150 mW of average power. Amplification of
      unstretched and stretched pulses was studied. Using chirped-pulse amplification,
      we obtained clean pedestal-free 420-fs pulses. Amplification of unstretched
      pulses produced 84-fs pulses with a broad pedestal.

PMID- 19855470
TI  - High-performance single-mode fiber-optic switch.
AB  - A piezoelectrically actuated four-port Mach-Zehnder switch with 30-micros
      switching time and 0.25-dB insertion loss is demonstrated at a wavelength of 1.3
      microm. The worst-case cross talk is below -21 dB for an arbitrary input
      polarization. The process of fabricating the switch from commercial fiber
      couplers with length matching of the interferometer arms is described.

PMID- 19855471
TI  - Thermal lens correction of a diode-pumped Nd:YAG laser of high TEM(00) power by
      an adjustable-curvature mirror.
AB  - Highly efficient TEM(00)-mode laser power of 11.5 W was obtained by the diode
      array side pumping of a Nd:YAG rod. We maintained efficient laser operation at
      all pump powers by correcting for the changing thermal lens with an adjustable
      curvature mirror.

PMID- 19855472
TI  - Femtosecond pulses from an all-solid-state Kerr-lens mode-locked Cr:LiSAF laser.
AB  - We report on an all-solid-state Kerr-lens mode-locked femtosecond laser. Using an
      intracavity-doubled mode-locked Nd:YLF laser with two Nd:YLF rods, we have
      produced 295 mW of light at 659 nm that pumps a Cr:LiSAF laser. Self-sustained
      Kerr-lens mode locking is achieved in the Cr:LiSAF laser with pulse durations as
      short as 90 fs.

PMID- 19855473
TI  - All-solid-state intracavity-doubled Nd:YLF laser producing 300 mW of 659-nm
      light.
AB  - A mode-locked Nd:YLF laser is described, which uses two diode-pumped Nd:YLF rods
      and intracavity doubling in LiB(3)O(5) to give an all-solid-state source of high
      beam-quality 659-nm red light suitable for pumping Kerr-lens-mode-locked
      Cr:LiSAF. Significant increases in the quantity of 659-nm light produced on
      active mode locking of the laser are characterized. Reductions in the noise
      characteristics of the 659-nm output by detuning the mode-locking frequency from
      cavity resonance indicate a preferential mode of operation for this device.

PMID- 19855474
TI  - Decoloration of yttrium orthovanadate laser host crystals by annealing.
AB  - Decoloration of a Czochralski-grown YVO(4) laser host is studied by evaluation of
      the optical absorption and the photoluminescence spectrum before and after
      annealing under various atmospheres. Decoloration of yellow asgrown crystals, as
      a result of the decrease in the absorption near the absorption edge, occurs
      independently of the air, N(2), and O(2) annealing atmospheres. The most dramatic
      decrease in the absorption is seen in N(2). Annealing in N(2) atmosphere is
      suggested to be effective for obtaining the highly transparent crystals.

PMID- 19855475
TI  - Ring-laser gyro with spatially resolved eigenstates.
AB  - The spatial resolution of laser eigenstates is applied to ring geometry. A
      bidirectional optical diode based on the Faraday effect and nonreciprocal
      intracavity losses is theoretically and experimentally investigated. This novel
      optical diode combined with spatial separation provides a biased gyro with no
      lock-in band.

PMID- 19855476
TI  - Effect of mode nonorthogonality in distributed-feedback lasers.
AB  - An analysis of the quantum noise in distributed-feedback lasers based on the
      Fokker-Planck equation has been developed to take into account the nonorthogonal
      nature of the laser modes. We have obtained numerical results of the steady-state
      solution of the single-mode operation that reveal the difference between the
      standard approach orthogonal laser modes and the realistic model (mode
      nonorthogonality included) for a distributed-feedback laser with nonvanishing end
      reflectivity and the complex coupling coefficient.

PMID- 19855477
TI  - Suppression of beam breakup in self-mode-locked Ti:sapphire lasers.
AB  - We show that thermal aberration in optically pumped solid-state lasers can lead
      to the breakup of the beam profile. Kerr lensing present in the self-mode-locked
      regime tends to reduce the beam size in the laser material; such a beam is less
      sensitive to the thermal aberration, and its shape becomes free of secondary
      lobes. The thermal aberration has also the effect of moving the optimal operation
      point for self-mode locking. Experimental results obtained with a Ti:sapphire
      laser support our theoretical results.

PMID- 19855478
TI  - High-speed analog complex-amplitude liquid-crystal light modulator.
AB  - A homogeneously aligned smectic A* liquid-crystal quarter-wave retarder is used
      to produce analog complex-amplitude modulation of light through the electroclinic
      effect. The device consists of a reflection-mode polarization rotative phase
      shifter enhanced by an asymmetric resonator. With an entrance mirror reflectivity
      of 70%, an analog modulation of 65% of a fringe was observed. The 10-90% response
      time of the liquid crystal was measured to be 25 micros at 25 degrees C.

PMID- 19855480
TI  - Three-dimensional reflective image reconstruction through a scattering medium
      based on time-gated Raman amplification.
AB  - We present reconstructions of a three-dimensional object imaged in reflection
      mode through a turbid medium, using time-gated Raman amplification. We
      demonstrate a less than 1-cm depth resolution at a laser-power-limited viewing
      distance of 8.5 attenuation lengths from an object with a rough metallic surface.
      We show that, even at a viewing distance of 10.5 attenuation lengths, the imaging
      system is power limited rather than backscatter limited.

PMID- 19855479
TI  - Phase-diversity correction of turbulence-induced space-variant blur.
AB  - Space-variant blur is encountered when objects extend beyond the isoplanatic
      patch associated with the intervening atmospheric turbulence. The method of phase
      diversity, used to estimate jointly the object and the aberrations, is
      generalized to accommodate turbulence-induced space-variant blur. This
      generalization utilizes a parametric model for the blur function that is
      constructed with multiple phase screens. Simulation results are presented that
      demonstrate the recovery of near-diffraction-limited imagery from phase-diversity
      imagery that has been degraded with rather severe anisoplanatism.

PMID- 19855481
TI  - Two- and four-beam magneto-optical trapping of neutral atoms.
AB  - We report the experimental realization of new stable three-dimensional schemes
      for trapping neutral cesium atoms in a vapor cell that use either two or four
      Gaussian laser beams. Probe-beam absorption is employed to characterize both
      types of trap, and densities of 2 x 10(8) and 1 x 10(10) cm(-3), respectively,
      are measured for the two-and four-beam traps. The two-beam trapping mechanism
      combines a longitudinal magneto-optical force with a transverse spontaneous
      radiation pressure force associated basically with the beam geometry. This
      theoretical analysis compares well with our experimental observations.

PMID- 19855482
TI  - Red sensitivity of dichromated cellulose triacetate as a holographic recording
      material.
AB  - The red sensitivity of dichromated cellulose triacetate holographic recording
      material without any dye sensitization is reported. We suggest that the
      sensitivity is due to the absorption at 590 nm of the intermediate Cr(V) formed
      in the reducing process of chromium from Cr(VI) to Cr(III). In the experiment,
      the real-time transmission gratings are recorded with 632.8-nm irradiation from a
      He-Ne laser.

PMID- 19855483
TI  - Noise gratings in bleached silver halide diffuse-object holograms.
AB  - Noise gratings in diffuse-object holograms recorded as volume phase holograms in
      bleached silver halide emulsion are experimentally analyzed. Measurements of the
      diffraction efficiency and the noise of the holograms are taken. The experimental
      results obtained show that there is a drop not only in the diffraction efficiency
      but also in the noise that is due to the presence of noise gratings.

PMID- 19855484
TI  - Time-domain holographic image storage.
AB  - We describe a practical approach to image storage in a coherent time-domain
      optical memory that can be readily implemented with existing technologies. In
      this approach, two-dimensional images are stored spectroholographically in narrow
      ( less, similar 1-MHz) frequency channels of a time-domain storage material by
      use of a low-power laser, with one image per channel. Advantages of this approach
      include fast single-frame recording time, variable playback speeds, and random
      frame access. Experimental results demonstrating the use of this approach for
      high-speed, long-term image storage in Eu(3+):Y(2)SiO(5) are presented.

PMID- 19855485
TI  - Polarization properties of degenerate four-wave mixing in flame OH.
AB  - The polarization properties of backward-box, degenerate four-wave mixing from OH
      molecules are measured in a flame and compared with theory. Ratios of signal
      intensities for different laser polarizations are shown to exceed perturbation
      theory predictions for a closed two-level system when optical intensity gratings
      are formed in the interaction volume. These results are shown to be inconsistent
      with population-nonconserving effects and are attributed to scattering from
      quenching-induced thermal density gratings.

PMID- 19855486
TI  - Optimization of a femtosecond ellipsometer for gold photoreflectance studies.
AB  - I develop a quantitative optimization procedure for femtosecond reflectance
      ellipsometer measurements. The femtosecond ellipsometer eliminates the need for
      separate thin-film reflectance and transmittance measurements and allows self
      consistent determination of dielectric index changes of optically thick films on
      arbitrary substrates. I verify the optimization procedure and use the femtosecond
      ellipsometric measurements to investigate the photoreflectance of an optically
      thick gold film. A comparison of the extracted real and imaginary dielectric
      function components reveals evidence of thermalized and nonthermalized hot
      electron populations.

PMID- 19855487
TI  - High-contrast ferroelectric liquid-crystal spatial light modulator.
AB  - The spatial light modulator based on total internal reflection at the
      ferroelectric liquid-crystal-glass interface has a 10(7):1 contrast ratio, a 250
      micros response time, and a lambda/8 transmitted wave-front uniformity. These
      properties make the spatial light modulator well suited to provide frequency-band
      excision in acousto-optic spectrum analyzers.

PMID- 19855488
TI  - Diffractive-optic polarization-sensing element for magneto-optic storage heads.
AB  - A cascaded planarized holographic optical sensor consisting of a combination of a
      leaky beam splitter and a polarization beam splitter is evaluated for possible
      use in magneto-optic data storage pickup heads. The performance requirements for
      each element are specified, and two cascaded grating designs are considered. In
      one design we reconstruct the gratings with the grating vector in the plane of
      incidence, using a half-wave plate. In the second design we reconstruct the
      gratings with the grating vector of the polarization beam splitter out of the
      plane of incidence without using a half-wave plate. The two systems are
      fabricated with gratings formed in dichromated gelatin emulsions, and they can
      detect 0.5 degrees rotations in the polarization state of an incident beam by use
      of a differential detection system.

PMID- 19855489
TI  - Birefringence reduction in side-written photoinduced fiber devices by a dual
      exposure method.
AB  - An in situ birefringence measurement in conjunction with an atomic force
      microscope study shows that the geometric asymmetry of the side-writing process
      is a major cause of the induced birefringence in grating-based fiber devices.
      Measured refractive-index profiles of UV-exposed fibers clearly show the
      asymmetry in the induced index change. We demonstrate the use of a dual-exposure
      technique for producing low-birefringence devices.

PMID- 19855490
TI  - Ultraviolet-induced permanent Bragg gratings in cerium-doped ZBLAN glasses or
      optical fibers.
AB  - A holographic method was used to write refractive-index gratings in ZBLAN
      fluoroziroconate glasses or fibers doped by a Ce concentration of 5000 or 10,000
      parts-in-10(6) weight. Direct pumping of the (2)F(5/2)-5d transitions of Ce(3+)
      ions near 245 nm resulted in a change in the refractive index. The photoinduced
      change partly recovered on a time scale of several hours at room temperature. The
      remaining change in the refractive index looked stable on a time scale of a
      month. This permanent change reaches 2 x 10(-5) at 1560 nm.

PMID- 19855491
TI  - Morphology-dependent resonances in eccentrically stratified spheres.
AB  - Calculations based on an exact theory have been made of the scattering properties
      of spherical particles possessing arbitrarily placed spherical inhomogeneities.
      The inclusions are homogeneous but of otherwise arbitrary composition and are
      limited in size only by that of the host. It has been found that a single
      inclusion, though having a volume of only 10(-6) that of the host, can produce
      large fluctuations in light scattered by the system as the inclusion passes
      through regions of high local intensity. The resonance spectrum of a glycerol
      droplet with inclusions centered in a hot spot reveals that the inclusions cause
      a spectral shift of the resonance peak. The directions of the shifts are
      consistent with the phase-matching conditions that must be met by photons
      traversing an orbit inside the host in order for a resonance to be sustained.
      Absorption spectra of systems with inclusions that are also large enough to
      sustain resonances are examined as well.

PMID- 19855492
TI  - Optical heterodyning with a frequency difference of 1 THz in the 850-nm range.
AB  - We report our recent progress on detection of large frequency difference (up to
      1.028 THz, Deltalambda = 2.5 nm) between two laser diodes at 852 nm, using a
      Schottky diode as harmonic mixer/detector. Using the 11th harmonic of a klystron
      operating at 93.5 GHz or the 991-GHz line of an optically pumped HCOOH far
      infrared laser, we were able to observe a signal-to-noise ratio of 2 dB in a 1
      MHz-resolution bandwidth.

PMID- 19855493
TI  - Paradox about quality values of dielectric resonators.
AB  - The pi-phase difference that exists between the reflecting and the refracting
      rays from a dielectric resonator results in a suppression of the energy leakage
      from the resonator. If the resonator is not illuminated by an external source of
      radiation but is, instead, supplied by an internal source, then the reflecting
      ray vanishes, and the rate of energy leakage increases. An exact wave-theory
      analysis shows that the quality value of the resonator is approximately
      quartered, which is considerable in both theory and applications of current
      interest.

PMID- 19855494
TI  - Reflective block optics for packaging of optical computing systems.
AB  - A new optical packaging technique, which we call reflective block optics, for
      optical computing systems is proposed and demonstrated experimentally. This
      technique is based on solid optics, which is advantageous with respect to
      stability, reliability, and alignability. Reflective lenses are used to attain
      high lens power, compactness, and a large space-bandwidth product. Glass blocks,
      cube beam splitters, and reflective optical elements are combined to form optical
      blocks. We can construct several optical systems by assembling the optical
      blocks.

PMID- 19855495
TI  - Accurate description of ultrawide-angle beam propagation in homogeneous media by
      Lanczos orthogonalization.
AB  - We demonstrate accurate modeling of ultrawide-angle beam propagation in
      homogeneous media by Lanczos orthogonalization for acceptable longitudinal step
      sizes. Accuracy is determined by comparison with solutions to the Helmholtz
      equation obtained by a band-limited Fourier series method.

PMID- 19855496
TI  - Parametric spatial solitary waves.
AB  - We consider the copropagation of three (pump, Stokes, and anti-Stokes) self
      trapped beams that interact through the parametric four-photon-mixing process in
      a (1 + 1 dimension) uniform self-focusing nonlinear medium. The stationary
      propagation involving three trapped beams is shown to be possible below a
      critical frequency shift when the phase difference between the three waves is
      either matched or highly mismatched. Most importantly, the steady-state solutions
      are found to be stable, as in the case of presence of only one soliton beam,
      except that the two (in-phase) fundamental stationary states launched in parallel
      will not return to their original states periodically after collision; rather,
      they may repel each other on collision and propagate in summetrically tilted
      directions thereafter with increasing separation.

PMID- 19855497
TI  - Quasi-phase-matched frequency doubling in bulk periodic polymeric structures.
AB  - A new technique for the fabrication of freestanding poled polymer films that uses
      a metallic film as the lifting-off layer is reported. This technique is used to
      make low-transmission-loss bulk periodic synthetic-crystals structures that
      satisfy a quasi-phase-matching condition for second-harmonic generation.
      Efficiency of the order of 10(-2)% is obtained for a thickness of 150 microm. The
      theoretical basis for determining the optimum phase-matching angle to maximize
      the second-harmonic conversion efficiency is discussed.

PMID- 19855498
TI  - Light-induced absorption in photorefractive strontium barium niobate.
AB  - Sr(0.59)Ba(0.41)Nb(2)O(6) and Sr(0.75)Ba(0.25)Nb(2)O(6) exhibit an intensity
      dependent absorption in the visible spectral range. We perform pump (green)-probe
      (red) measurements and find variation as high as 0.45 cm(-1) in the absorption
      coefficient, which depends significantly on the polarization of the probe light
      beam. Our results indicate a nonexponential dark decay time of the induced
      absorption and suggest that the trapping potential of the shallow traps varies
      significantly from one trap to another (multiple isolated shallow traps).

PMID- 19855499
TI  - Stability of photorefractive spatial solitons.
AB  - We present a theoretical analysis of the stability of photorefractive spatial
      solitons along with experimental results that show that the solitons are stable
      for small-scale perturbations but break down when the perturbations exhibit a
      transverse scale comparable with the soliton size (cross section).

PMID- 19855500
TI  - Effect of subharmonics on two-wave gain in Bi(12)SiO(20) under alternating
      electric fields.
AB  - It is demonstrated that the emergence of subharmonics during two-wave mixing in a
      Bi(12)SiO(20) photorefractive crystal under applied alternating electric fields
      will markedly reduce two-wave gain. The repetition frequency at which the
      observed drop in two-wave gain appears is correlated with threshold conditions
      for the subharmonic instability for a wide range of experimental parameters.

PMID- 19855501
TI  - Interacting gray solitons.
AB  - We present what is to our knowledge the first general theory for describing
      interacting well-separated gray spatial solitons, propagating in an arbitrary
      self-defocusing nonlinearity. It reveals why two dark solitons will in general
      repel, becoming less dark as they propagate. The results are illustrated with
      analytic expressions for the Kerr and the saturating nonlinearities.

PMID- 19855503
TI  - Cancellation of four-wave mixing in a single-mode fiber by midway optical phase
      conjugation.
AB  - Cancellation of waves generated by four-wave mixing (FWM) in a single-mode fiber
      by use of midway optical phase conjugation is proposed and analyzed, and the
      possible power reduction is estimated. Effective cancellation of FWM is
      demonstrated with phase-conjugate waves generated by forward FWM in a zero
      dispersion single-mode fiber, and a power reduction ratio of -13.9 dB is achieved
      in experimental three-channel transmission along a 40-km dispersion-shifted
      fiber.

PMID- 19855502
TI  - Phase-controlled transistor action by cascading of second-order nonlinearities in
      KTP.
AB  - We demonstrate a 4.6-to-1 modulation depth imposed on the fluence of an intense
      1.06-microm picosecond pulse by varying the relative phase of a weak second
      harmonic control pulse under near phase-matched conditions. This transistorlike
      action is based on quadratic nonlinearities in KTP.

PMID- 19855504
TI  - Self-frequency doubling in Nd,Sc(2)O(3):LiNbO(3) at room temperature.
AB  - Self-frequency doubling is reported in a Nd,Sc(2)O(3):LiNbO(3) single crystal.
      The Sc(2)O(3) doping produced room-temperature (20 degrees C) 90 degrees
      noncritical phase matching (theta = 90 degrees C). Under quasi-cw conditions,
      0.14 mW of frequency-doubled 546-nm radiation was produced. The pump-to-green
      light conversion efficiency was 11%/W with a 25-mW absorbed input power lasing
      threshold. Only the fundamental 1092-nm s-polarized oscillation was produced,
      rather than the p-polarized output, as reported for Nd,MgO:LiNbO(3). This
      simplified the cavity by elimination of the Brewster window needed to force the s
      polarized output required for type I phase matching.

PMID- 19855505
TI  - Chirped in-fiber Bragg gratings for compensation of optical-fiber dispersion.
AB  - A linearly chirped in-fiber Bragg grating is reported that can compensate at 1549
      nm for the dispersion [ approximately -19 ps/(nmkm)] of standard
      telecommunications optical fiber optimized for 1300-nm operation.

PMID- 19855506
TI  - Adiabatic coupled-mode filters with linear phase.
AB  - Techniques for obtaining linear phase response in wideband coupled-mode filters
      with variable detuning are described.

PMID- 19855507
TI  - Silicon optical waveguides with buried-CoSi(2) cladding layers.
AB  - We report a new Si waveguide that has a buried, metallike cladding. Infrared
      light propagates in a crystal Si layer atop a 50-nm film of buried CoSi(2) formed
      by implantation. Experiments in a 20-microm Si structure at the 1.3-microm
      wavelength show propagation losses below 2.5 dB/cm for TE(0) and TM(0). Results
      agree with theory. We also constructed two vertically integrated Si slab
      waveguides bounded below by CoSi(2) cladding layers.

PMID- 19855508
TI  - 3.5-W Q-switched 532-nm Nd:YAG laser pumped with fiber-coupled diode lasers.
AB  - A diode-pumped laser with greater than 11 W of cw 1064-nm output power and 3.5 W
      of frequency-doubled average power at a 50-kHz pulse repetition frequency has
      been developed. A single Nd:YAG rod was pumped with the combined output of three
      fiber-coupled diode-laser arrays. Each pump laser was capable of 10 W of cw
      output power. The fiber output of each pump laser was first collimated and then
      focused with a single lens onto one end of a Nd:YAG rod. The resonator mirrors
      for the L-shaped cavity were selected such that thermal lensing in the laser
      crystal was mostly compensated. The 532-nm output beam quality factor (M(2)) was
      less than 1.5.

PMID- 19855509
TI  - 82% Efficient continuous-wave frequency doubling of 1.06 microm with a monolithic
      MgO:LiNbO(3) resonator.
AB  - We describe a frequency-doubling monolithic standing-wave resonator made of
      MgO:LiNbO(3) with dielectric mirror coatings for impedance matching near 100 mW
      input power and near-optimum nonlinear coupling. An external conversion
      efficiency of 82% has been achieved.

PMID- 19855510
TI  - Efficient 100-W Nd:YAG laser operating at a wavelength of 1.444 microm.
AB  - Efficient laser emission of flash-lamp-pumped Nd:YAG rods at a wavelength of
      1.444 microm is reported. A maximum average output power of 100 W at pulse
      energies of 5.5 J and a pulse duration of 0.65 ms was achieved. The highest
      electrical-to-optical overall efficiency of 1.3% was attained with a single
      elliptical silver pump cavity with europium-doped quartz as a spectral filter.
      The 1.444-microm performance as well as the output characteristics at 1.064 and
      1.32 microm of Nd:YAG were investigated as a function of doping concentration and
      rod diameter.

PMID- 19855511
TI  - Amplitude noise reduction in semiconductor lasers with weak, dispersive optical
      feedback.
AB  - We present the theory and measurements of the amplitude noise spectrum from a
      semiconductor laser with weak optical feedback (P(fb)/P(out) approximately 10(
      6)) from an external cavity containing an element of dispersive loss. The laser
      noise is found to be reduced over most of the low-frequency spectrum, although an
      increase in the noise is observed at frequencies corresponding to multiples of
      the external-cavity free spectral range. The low-frequency noise reduction
      closely follows theoretical predictions, and a reduction of as much as 7 dB is
      measured at an injection current of 1.5 times the threshold current. The
      potential of this method for contributing to the production of amplitude-squeezed
      light is discussed.

PMID- 19855513
TI  - Negative binary arithmetic algorithms for digital parallel optical computation.
AB  - Based on a negative binary number system, an algorithm with weighted-shifted
      addition, parallel-array multiplication, and a two-stage-array complex operation
      is proposed to carry out the multiplication of two complex numbers. The complex
      multiplication is performed without signs, carries, and recoding. The algorithm
      is suitable for optical implementation, and an optical parallel architecture is
      suggested. The experimental result is also given.

PMID- 19855512
TI  - Single lithium niobate crystal for mode selection and phase modulation in a
      tunable extended-cavity laser diode.
AB  - A 1540-nm external-cavity laser diode with an intracavity electro-optic
      wavelength tuner is demonstrated. Coarse- and fine-wavelength tuning is achieved
      with a single lithium niobate wavelength tuner. One section of the crystal is
      used as a tunable-wavelength filter to tune the wavelength by mode hopping. The
      other operates as a phase modulator to change the optical length of the cavity
      and to tune the wavelength continuously. Coarse tuning by mode hopping is
      obtained over a range of 5.3 nm with a tuning rate of 580 MHz/V. Continuous
      tuning is obtained over 82% of the free spectral range of the cavity. The
      wavelength switching time is 10 ns for the cavity used.

PMID- 19855514
TI  - Phase-only filter with improved discrimination.
AB  - The optimization of a phase-only filter (POF) in terms of discrimination
      capability is presented. The notion of a phase-difference histogram and its
      modification are proposed for selecting the support function of the POF. Some
      numerical results obtained with the conventional POF and the optimized POF are
      given. The discrimination capability is increased significantly.

PMID- 19855515
TI  - Effect of radiation trapping on fluorescence lifetime and emission cross section
      measurements in solid-state laser media.
AB  - Radiation trapping causes significant lengthening of the measured fluorescence
      lifetime in optically thin solid-state laser gain media, which leads to
      underestimates of the stimulated emission cross section by as much as 30%. A
      measurement technique is demonstrated that greatly reduces radiation trapping in
      Yb:YAG, a prototypical quasi-three-level laser medium. The radiative lifetime of
      the (2)F(5/2) manifold was measured to be 0.951 ms at 300 K, which is more than
      10% lower than any previous measurement. This more-accurate radiative lifetime
      gives a 1.03-microm peak effective stimulated emission cross section of 2.3 x 10(
      20) cm(2). Our measurement technique is expected to be most relevant for three
      level and quasi-three-level laser media.

PMID- 19855516
TI  - Helium spectroscopy using an InGaAs laser diode.
AB  - Absorption spectroscopy in (3)He and (4)He has been performed with an InGaAs
      single-mode distributed Bragg reflection laser diode. The laser source provides
      as much as 120 mW of single-mode, single-frequency output in the 1083-nm region
      of the spectrum. Frequency tuning of the laser diode output by means of the
      junction temperature allows for mode-hop-free scanning of the entire 2(3)S-2(3)P
      manifold in both the (3)He and (4)He absorption spectra. The authors believe this
      to be the first report of semiconductor laser spectroscopy at this wavelength.
      Such a device will have significant applications in optical pumping, atomic
      cooling and trapping, fundamental nuclear studies, magnetometry, and gas
      dynamics.

PMID- 19855517
TI  - Bound-bound transition in a field with a nonzero average cube in a molecule in a
      Langmuir-Blodgett film.
AB  - Interference of single- and two-photon transitions that is due to an E(2omega) +
      E(2omega) field may result in asymmetry of the excitation diagram and hence in
      reorientation of molecules in a Langmiur-Blodgett film.

PMID- 19855518
TI  - Increase of the space-bandwidth product of computer-generated near-field
      holograms by optical means.
AB  - Computer-generated near-field holograms are well suited to display numerical data
      in three-dimensional pictorial form. The available computer capacity and
      recording facility frequently limit the attainable space-bandwidth product. An
      optical technique that can improve it and provide comfortable viewing conditions
      is presented.

PMID- 19855519
TI  - Entropy-based study of imaging quality in holographic optical elements.
AB  - A method for obtaining the best image plane for holographic optical elements by
      the use of the concept of entropy is described. This method is applied to in-line
      holographic lenses with different values of spherical aberration. Numerical
      results show that for holograms with large aberrations the best image plane
      (obtained by the use of the concept of entropy) is different from the minimum
      aberration-variance plane.

PMID- 19855520
TI  - Wavelength-multiplexed reconfigurable interconnect using a volume holographic
      lens array.
AB  - Wavelength-multiplexed holograms have been used to store log(N) stages of an N
      node butterfly interconnect. We recorded and reconstructed the holograms, using
      LiNbO(3) over a range of 790 to 800 nm. The wavelength separation can be as
      little as 0.6 nm between holograms. We implemented the interconnect by recording
      a 4 x 4 array of elements that contained five superimposed lenses each. These
      lenses formed a semi-space-variant optical interconnect with a space-bandwidth
      product larger than 2 x 10(3) for each 2 mm x 2 mm lens.

PMID- 19855521
TI  - Laser-induced thermal acoustics: simple accurate gas measurements.
AB  - Laser-induced thermal acoustics (LITA), an optical four-wave mixing technique,
      has been used for sensitive measurement of the sound speed, thermal diffusivity,
      acoustic damping rate, and complex susceptibility of a gas. In LITA, laser
      induced acoustic waves scatter laser light into a coherent, modulated signal
      beam. A simple expression accurately describes the signal. Atmospheric sound
      speeds accurate to 0.5% and transport properties accurate to 30% have been
      measured in a single shot without calibration. LITA spectra have been taken of
      weak spectral lines of NO(2) in concentrations of less than 50 parts in 10(9).
      Signal reflectivities up to 10(-4) are estimated.

PMID- 19855522
TI  - Adaptive bacteriorhodopsin-based holographic correlator for speed measurement of
      randomly moving three-dimensional objects.
AB  - An adaptive correlator system is presented that uses a bacteriorhodopsin film as
      the active holographic material. Because M-type holography with bacteriorhodopsin
      films is used, the TV frame rate is met at fairly low intensities. No limitations
      arising from the heterodyne operation of the dual-axis joint-Fourier-transform
      correlator were observed. The system's capability to monitor autonomously the
      speed of an object moving randomly in the whole viewing field of a video camera
      is demonstrated.

PMID- 19855523
TI  - Phase method of measuring a signal in fiber-optic birefringence-type sensors.
AB  - A phase method of measuring the phase retardation that occurs in the fiber-optic
      birefringence-type sensor and that is caused by the signal to be detected has
      been studied both theoretically and experimentally. The method is based on a
      nonmechanical low-frequency rotation of the light polarization plane at the input
      to the primary transducer of the sensor, which is provided by three incoherent
      light sources with their intensities modulated by periodic oscillations that are
      phase shifted by 2pi/3 rad with respect to one another. The phase-retardation
      measurement accuracy determined on an experimental basis was no worse than 0.1%
      full scale over a 2pi-rad range.

PMID- 19855524
TI  - Modeling of soliton-dragging logic gates with gain.
AB  - Islam [Ultrafast Fiber Switching Devices and Systems (Cambridge U. Press,
      Cambridge, 1992)] and Islam and co-workers [in Digest of Integrated Photonics
      Research (Optical Society of America, Washington, D.C., 1992)] have proposed
      adding a lumped gain to soliton dragging logic gates in order to relax the timing
      constraints. Three reduced models are used to study the dragging gate with
      discrete gain and are compared with complete simulations. The most accurate of
      these methods, the variational method with chirp, predicts the time shift of the
      control pulse with an accuracy within 12% at all initial separations of the
      control and signal pulses. This method also predicts an increase by a factor of 2
      in the timing window, a result that is consistent with complete simulations and
      experiments.

PMID- 19855525
TI  - Moment definition of the pointing stability of a laser beam.
AB  - A new definition of the pointing stability of a laser beam is proposed. It is
      derived from the superposition integral between the optical field and a
      misaligned version of itself. This approach permits the characterization of the
      pointing stability with a single number, while taking into account the intensity
      and phase features of the beam. This pointing stability criterion is invariant
      under propagation and can be related to the moment definitions of beam size,
      divergence, and quality. The definition is also suggestive of an experimental
      measurement procedure.

PMID- 19855526
TI  - Polarization of light scattered from slightly rough dielectric film.
AB  - We found that a slightly rough thin dielectric film polarizes diffusely scattered
      light. There is a discrete set of angles of incidence and observation for which
      the intensity of a nonspecular diffuse P-polarized component is significantly
      greater than that for S polarization.

PMID- 19855527
TI  - Midwave and long-wave infrared radiance and clutter at the ocean-sky horizon.
AB  - A statistical analysis is presented for the mean and the clutter radiance emitted
      by the ocean surface near the horizon and in the absence of direct solar
      illumination. The calculated midwave and long-wave radiances are given as
      functions of the environmental and optical parameters and agree with
      experimentally measured radiance profiles to within 20%. A simple expression for
      the calculated radiance as a function of wind speed and look direction is
      obtained by linearizing the radiance as a function of the wave slope.

PMID- 19855528
TI  - Fresnel diffraction and the fractional-order Fourier transform.
AB  - Fractional-order Fourier transforms are adapted to the mathematical expression of
      Fresnel diffraction, just as the standard Fourier transform is adapted to
      Fraunhofer diffraction. The continuity of fractional Fourier transforms with
      respect to their orders corresponds to the continuity of wave propagation, and
      their composition is in accordance with the Huygens principle.

PMID- 19855529
TI  - Thermo-optic coefficients of LiNbO(3), LiIO(3), and LiTaO(3) nonlinear crystals.
AB  - Thermo-optic coefficients (dn/dT) determine the temperature characteristics of
      nonlinear-optical laser devices. These coefficients are analyzed critically by
      use of a new model for what is to the author's knowledge the first time to find
      refractive indices at any operating temperature and wavelength for pure
      stoichiometrically grown LiNbO(3), LiIO(3), and LiTaO(3) crystals. This model is
      based on the thermal expansion coefficient, the temperature coefficient of the
      excitonic band gap, and a newly introduced isentropic band gap that lie in the UV
      region instead of on consideration of the spontaneous polarizability.

PMID- 19855530
TI  - Pulsating neuron produced by electron-trapping materials.
AB  - We report our results from the study of the dynamics of electron-trapping
      materials (ETM's) under simultaneous illumination of pulsed blue light and
      constant IR light. By combining the dynamic property of ETM with the S-shaped
      nonlinear I-V characteristic of a programmable unijunction transistor, we produce
      an optoelectronic pulsating neuron. A proof-of-concept experiment successfully
      produces oscillations and demonstrates the great potential of using ETM's to
      implement dense arrays of pulsating neurons.

PMID- 19855531
TI  - Submillisecond photorefractive response time of KNbO(3):Rb(+).
AB  - We investigate the photorefractive response time of diffraction gratings in Rb(+)
      doped KNbO(3) crystals. Two components of charge carriers, with different
      response times, are found to contribute to the photoinduced index gratings. One
      component, which contributes to approximately 70% of the index grating, shows a
      submillisecond rise time when the total intensity of the writing beams is larger
      than 5 W/cm(2). The dependence of the response time on the light intensity and
      the grating wave vector is also investigated.

PMID- 19855532
TI  - Ultrabroad-bandwidth multifrequency Raman generation.
AB  - We report on the modeling of transient stimulated rotational Raman scattering in
      H(2) gas. We predict a multifrequency output, spanning a bandwidth greater than
      the pump frequency, that may be generated without any significant delay with
      respect to the pump pulses. The roles of dispersion and transiency are
      quantified.

PMID- 19855533
TI  - Suppression and enhancement of dye lasing and stimulated Raman scattering from
      various dye-doped liquid spheres.
AB  - The observation of suppression or enhancement of dye lasing and stimulated Raman
      scattering (SRS) from various dye-doped liquid droplets, in which SRS from the
      initial pumping wavelength appeared in shorter and longer wavelengths of various
      dye fluorescence regions, is reported; SRS from the dye-lasing wavelengths
      (double resonances) and stimulated resonance Raman scattering of dyes are
      included. Furthermore, the contribution to SRS of the dye fluorescence (depending
      on dye concentration and different dyes) and dye-lasing suppression that is due
      to stimulated resonance Raman scattering is also described.

PMID- 19855534
TI  - Linewidth-narrowing mechanism in lasers by nonlinear wave mixing.
AB  - We propose a linewidth-narrowing mechanism in lasers by nonlinear absorptive wave
      mixing of the counterpropagating beams in the cavity. We give a theoretical
      analysis and report on a demonstration of the effect with an erbium-doped fiber
      laser. The system also exhibits bistability in the dependence of the oscillation
      intensity versus pump power.

PMID- 19855535
TI  - Determination of the refractive index of a bacteriorhodopsin film.
AB  - The wavelength-dependent refractive index of a bacteriorhodopsin thin film is
      measured by the use of a modified critical-angle technique. The effect of the
      host bovine skin gelatin on the refractive index is analyzed. The measured data
      on the thin film can be useful for system applications. The methods and
      procedures are generally applicable to any optically absorbing thin films.

PMID- 19855536
TI  - Dynamic self-pumped phase-conjugating mirror based on the bacteriorhodopsin
      variant D96N.
AB  - A self-pumped, phase-conjugating mirror (diameter 17 mm) is described that
      contains the bacteriorhodopsin variant D96N as the photoactive material. Resonant
      reflectivities up to 30% were obtained with an intensity of 25 mW/cm(2) at 647
      nm. Rise times of less than 1 ms were observed with an intensity of 500 mW/cm(2)
      at 532 nm. Wave-front restoration with spatial light modulators as the dynamic
      input device was demonstrated, and the dependence of the reflectivity on the
      intensity and polarization was analyzed. The reflectivity shows no significant
      decrease with increasing angle between the pump and signal beams as a result of
      the high resolution of the bacteriorhodopsin films.

PMID- 19855537
TI  - Trapping the grating envelope in bulk photorefractive media.
AB  - We introduce the concept of traveling grating envelopes to study the erasure
      dynamics in bulk photorefractive media. This new technique provides considerable
      physical insight into the observed photorefractive transients. We propose and
      demonstrate experimentally, in a Ce-doped SBN:60 crystal, two novel ways of
      extending the grating lifetime by trapping the grating envelope inside the
      medium. The incident beam ratio and the readout geometry have the largest effect
      on how long the grating can be read out.

PMID- 19855538
TI  - Observation of angularly tilted subharmonic gratings in photorefractive bismuth
      silicon oxide.
AB  - A new subharmonic regime in photorefractive bismuth silicon oxide has been
      discovered by the use of the running-grating technique. In this regime the
      subharmonic grating splits into two gratings that are angularly tilted with
      respect to the fundamental grating. These observations necessitate an extension
      of previously proposed theories.

PMID- 19855539
TI  - Birefringence modulation in fiber-optic phase modulators.
AB  - We report an unusually large birefringence modulation in fiber-optic phase
      modulators formed with cylindrical piezoelectric transducers when driven at a few
      hundred kilohertz. The magnitude of the birefringence modulation is a strong
      function of modulation frequency. A simple model is used to explain the
      phenomenon, and the theoretical predictions agree well with the experimental
      results.

PMID- 19855540
TI  - Symmetric and asymmetric fiber loop mirrors for observing guided-acoustic-wave
      Brillouin scattering in polarization-maintaining fibers.
AB  - A new scheme of symmetric and asymmetric fiber loop mirrors is proposed to
      identify clearly the polarized guided-acoustic-wave Brillouin scattering spectra
      with multimode laser sources. The guided-acoustic-wave Brillouin scattering
      spectra in PANDA fibers in the low-frequency region are unambiguously confirmed
      with this scheme.

PMID- 19855541
TI  - Diode-pumped passively Q-switched picosecond microchip lasers.
AB  - Passively Q-switched 1.064-microm microchip lasers have been constructed from
      thin pieces of Nd(3+):YAG bonded to thin pieces of Cr(4+):YAG. When pumped with
      the unfocused 1.2-W output of a fiber-coupled diode, these devices produced 11
      microJ pulses of 337-ps duration at a pulse repetition rate of 6 kHz in a single
      frequency TEM(00) mode. The peak power of the lasers was in excess of 180
      MW/cm(2).

PMID- 19855542
TI  - Efficient seeding of a Raman amplifier with a visible laser diode.
AB  - Recent developments in tunable laser diodes now make it possible to do injection
      seeding of a quantum-limited Raman amplifier. We present data from an experiment
      in which a tunable laser diode in the visible was injected into a Raman amplifier
      with a coupling efficiency of 65% +/- 45%. This efficiency approaches the
      theoretical limit of 100% and is much larger than the 0.1-0.2% coupling
      efficiency reported in the literature for a comparable experiment when an
      infrared laser diode is used.

PMID- 19855543
TI  - Difference-frequency generation of 4-microm radiation from Nd:YAG lasers.
AB  - More than 30 mJ of mid-IR 4-microm energy was generated with difference-frequency
      mixing of 1.064- and 1.444-microm Nd:YAG laser pulses in a lithium niobate
      crystal. The energy conversion efficiency in converting from the pump at 1.064
      micro to the mid-IR at 4.043-micro was ~5.5%. The amount of 4-micro output
      produced was limited by optical damage to the lithium niobate crystal. In this
      experiment, the optical damage threshold occurred at a peak intensity of 300
      MW/cm(2).

PMID- 19855544
TI  - Intracavity frequency doubling of a continuous-wave, diode-laser-pumped neodymium
      lanthanum scandium borate laser.
AB  - Neodymium-doped lanthanum scandium borate [Nd:LaSc(3)(BO(3))(4)] is a new
      material for efficient and compact diode-pumped solid-state lasers. A simple
      plane-plane 3-mm-long resonator is formed by a coated Nd(10%):LaSc(3)(BO(3))(4)
      crystal and a coated potassium titanyl phosphate (KTP) crystal. The second
      harmonic output power at 531 nm is 522 mW at 2.05-W incident pump power of the
      diode laser. The corresponding optical efficiency is 25%, and the conversion
      efficiency from the fundamental to the second harmonic is 55%. The wellknown
      chaotic power fluctuations of intracavity frequency-doubled lasers (green
      problem) are avoided by use of a short KTP crystal, between 0.5 and 2 mm in
      length.

PMID- 19855545
TI  - High-repetition-rate femtosecond optical parametric oscillator based on
      RbTiOAsO(4).
AB  - A high-repetition-rate Ti:sapphire-pumped femtosecond optical parametric
      oscillator based on the new nonlinear-optical crystal RbTiOAsO(4) is described.
      Tuning from 1.03 to 1.3 microm in the signal branch and from 2.15 to 3.65 microm
      in the idler branch with powers as high as 250 mW in the signal and 200 mW in the
      idler is presented. The possibility of extending the tuning range beyond 3.65
      microm is discussed.

PMID- 19855546
TI  - Multiterawatt 30-fs Ti:sapphire laser system.
AB  - A near-diffraction-limited transform-limited multiterawatt laser system that
      produces approximately 30-fs 125-mJ 800-nm pulses at a repetition rate of 10 Hz
      has been constructed. Methods for the control of femtosecond time-scale phase and
      amplitude distortions have been developed and implemented.

PMID- 19855547
TI  - Laser transition characterization by spectral and thermal dependences of the
      transient oscillations.
AB  - Spectroscopic measurements on (4)F(3/2) - (4)I(11/2) and (4)F(3/2) - (4)I(9/2)
      transitions for a Nd(3+)-doped fiber laser demonstrated that the wavelength
      dependence of the relaxation oscillations provides a simple method to distinguish
      threeand four-level transition. Spectral analysis of relaxation oscillations in a
      tunable Er(3+)-doped fiber laser was performed at liquid-nitrogen temperature,
      and results were compared with measurements at room temperature. It was found
      that the relaxation oscillation frequency depends on the occupation of the
      terminal level and thus is directly related to the absorption cross section.
      Using this method, we show that laser transitions at lambda > 1555 nm become four
      level at T = 77K.

PMID- 19855548
TI  - Neodymium-doped tellurite single-mode fiber laser.
AB  - A single-mode Nd(3+)-doped tellurite glass fiber laser operating at 1.061 microm
      is described. We believe this is the first demonstration of a single-mode fiber
      laser in tellurite glass. A lasing threshold of 27 mW of 818-nm absorbed pump
      power and a slope efficiency output power versus pump power of 23% emitted from
      one end were observed in the fiber cavity with 11.9% Fresnel reflection at both
      ends.

PMID- 19855549
TI  - Optical second-harmonic generation induced by a dc electric field at the Si
      SiO(2) interface.
AB  - For what is to our knowledge the first time, electric-field-induced optical
      second-harmonic generation (SHG) is studied at the Si-SiO(2) interface by the use
      of a metal-oxide-semiconductor (MOS) structure. The crystallographic anisotropy
      of this phenomenon is studied for MOS structures. Experimental results indicate
      that the MOS technique of dc electric-field application to the Si-SiO(2)
      interface can be effectively used for studying electroinduced effects on SHG.

PMID- 19855550
TI  - Ultrafast, all-silicon light modulator.
AB  - An ultrafast, all-silicon light-intensity modulator is proposed. The carrier
      refraction effect is used to modulate the refractive index of silicon. An
      electric-field-induced Bragg reflector on a silicon-on-insulator optical
      waveguide efficiently converts the small modulation of the index of refraction
      into light-intensity modulation. A modulator with 300-microm interaction length
      is expected to have a modulation depth of ~40% with 5-V bias. Being based on free
      carrier depletion, this modulator is expected to have a bandwidth limited only by
      the RC time constant, which is calculated for a sample device to be ~40 GHz.

PMID- 19855551
TI  - Dual-wavelength actively mode-locked laser-diode array with an external grating
      loaded cavity.
AB  - We report the generation of dual-wavelength picosecond pulses by use of a
      commercial laser-diode array. The laser cavity incorporated a folded dispersive
      delay line with a V-shaped double-stripe mirror. The spectral separation of the
      laser output at the two wavelengths can be tuned from 2 to 11 nm. The actively
      mode-locked pulse widths at the two wavelengths were both 29 ps. Cross
      correlation and power-spectrum measurements indicated that the two-color pulses
      were synchronized with an absolute timing jitter of less than 1 ps (instrument
      limited).

PMID- 19855552
TI  - Effect of delayed nonlinear response on femtosecond optical pulse compression by
      use of an organic crystal-cored fiber in the normal dispersion region.
AB  - We investigate the effect of delayed nonlinear response time on pulse
      compression, using an organic crystal-cored fiber in the normal dispersion
      region. With up to third-order phase compensation, a 100-W, 100-fs hyperbolic
      secant pulse is compressed to ~10 fs with a delayed nonlinear response time as
      well as without it. It is shown that third-order phase adjustment can compensate
      for the phase asymmetry in the frequency domain that is induced by the effect of
      the delayed nonlinear response.

PMID- 19855553
TI  - Polarization effects and nonlinear switching in fiber figure-eight lasers.
AB  - We have developed a novel experimental procedure that allows us to quantify how
      polarization effects determine the passive mode locking of an optical fiber
      figure-eight laser. Based on our measurements, we have performed numerical
      simulations demonstrating that the nonlinear switching within this laser operates
      in a manner contrary to that described by the conventional theory of passive mode
      locking with a fast saturable absorber.

PMID- 19855554
TI  - Fourth-order dispersion-limited solitary pulses.
AB  - We analyze the performance of a Ti:sapphire self-mode-locked laser with near-zero
      second- and third-order dispersion. Our simulations show that, in the presence of
      fourth-order dispersion, solitary laser pulses can be supported within a wide
      parameter range, close to the experimental values of these parameters. We also
      conclude that it is possible to generate pulses much shorter than 10 fs if fourth
      order dispersion is further reduced.

PMID- 19855555
TI  - Passive mode locking and dispersion measurement of a sub-100-fs Cr(4+):YAG laser.
AB  - We report the passive mode locking of a Cr(4+):YAG laser by use of a moving
      mirror and the generation of pulses as short as 70 fs by use of Kerr-lens mode
      locking. The intracavity dispersion has been measured, and the laser performance
      has been related to water absorption lines.

PMID- 19855556
TI  - Continuous view of dc-balanced images on a ferroelectric liquid-crystal spatial
      light modulator.
AB  - A scheme is presented that permits a continuous view of an image displayed on a
      dc-balanced ferroelectric liquid-crystal-on-silicon spatial light modulator. I
      develop the theory and present experimental results, using a 256 x 256
      ferroelectric liquid-crystal-on-silicon spatial light modulator. It is shown that
      both halves of the dc-balanced cycle can be made to produce identical outputs
      even when the illumination is polychromatic and the spatial light modulator
      liquid-crystal layer thickness is not an ideal half-wave plate and for an
      arbitrary liquid-crystal switching angle.

PMID- 19855557
TI  - Two-photon spectroscopy of the 6S(1/2) ? 6D(5/2) transition of trapped atomic
      cesium.
AB  - Two-photon spectroscopy of atomic cesium confined and cooled in a magneto-optical
      trap is reported. The hyperfine structure of the 6D(5/2) state is determined with
      1% accuracy. New capabilities for studying ac Stark shifts and kinetic transport
      for cold atoms are suggested.

PMID- 19855558
TI  - Axial irradiance for spherically aberrated holographic optical elements.
AB  - The effect of third-order balanced spherical aberration on the axial irradiance
      of holographic lenses is considered. It is shown that the number of principal
      maxima of axial irradiance increases for large aberrations, and the position of
      these points can be different from the position of the minimum aberration
      variance point.

PMID- 19855559
TI  - Electric-field-switchable stratified volume holograms in photorefractive
      polymers.
AB  - Two- and four-layer stratified volume holograms have been fabricated from the
      photorefractive polymeric material poly(methyl methacrylate): (1,3-dimethyl-2,2
      tetramethylene-5-nitrobenzimidazoline):C(60) and characterized by holographic
      four-wave mixing experiments. Coherent addition of diffracted fields from the
      individual layers is observed, leading to a diffraction efficiency that increases
      with the square of the active layer thickness. Electricfield switching of the
      diffraction efficiencies of individual layers is demonstrated. The angular
      selectivity of the diffraction efficiency is also characterized for one, two, and
      four active layers. The angular width of the peaks narrows with increasing total
      structure thickness in agreement with theory.

PMID- 19855560
TI  - Error correction for increasing the usable capacity of photorefractive memories.
AB  - Conventional error-correction coding techniques can be used to reduce the minimum
      signal-to-noise ratio required for achievement an acceptable bit-error rate and
      can therefore be used to increase the maximum number of pages that can be stored
      in a photorefractive memory. Because error-correction bits will exact some cost
      per page in terms of memory capacity, we address the question of when the gain in
      capacity surpasses this cost. It is found that a factor-of-2 improvement in
      capacity can be readily achieved.

PMID- 19855561
TI  - Velocimetry of gas flows using degenerate four-wave mixing.
AB  - A method of velocimetry of gaseous flows based on resonant degenerate four-wave
      mixing (DFWM) is described. Spatially resolved velocity measurements are derived
      from Doppler shifts of DFWM signals generated in NOseeded into flows of air or
      N(2). Velocities in the range of 60 to 200 ms(-1) have been measured with an
      uncertainty of +/-30 ms(-1).

PMID- 19855562
TI  - Tomographic imaging of fluid flows by the use of two-tone frequency-modulation
      spectroscopy.
AB  - Diode laser absorption measurements obtained with two-tone frequency-modulation
      spectroscopy (TTFMS) are combined with tomography to produce spatially resolved
      quantitative images of fluid flows. The high sensitivity, good accuracy, and high
      stability of TTFMS absorption measurements permit optical-absorption tomography
      to be performed with low noise on extremely weakly absorbing objects. The method
      is demonstrated on a small oxygen flow with a GaAlAs diode laser operating near
      760 nm and with an absorption sensitivity of 1:10(6).

PMID- 19855563
TI  - Two-color Brillouin ring laser gyro with gyro-compassing capability.
AB  - We investigated the gyro-compassing capability of a Brillouin ring laser gyro set
      up in a two-color operation. Two counterpropagating pump lasers initiated two
      Brillouin ring lasers on different resonances of a fiber-optic ring resonator
      cavity, which excluded the mutual intracavity interaction between both
      counterpropagating Brillouin lasers. Additionally minimizing the external
      feedback channels of the individual Brillouin lasers allowed for high-resolution
      measurements, e.g., the horizontal component of the Earth's rotation rate (10.0
      degrees /h at Uberlingen, Germany, which corresponded to a beat frequency of 6.85
      Hz).

PMID- 19855564
TI  - Broadband high-optical-density filters in the infrared.
AB  - A new concept for the design of broadband (2-25 microm and beyond) neutral
      density filters in the infrared region without etaloning effects is proposed and
      demonstrated. One important aspect of the technique is to use metallic-thin-film
      (10-200-nm-thick) multilayer combinations deposited onto different substrates
      (ZnSe, CdTe, Lexan). Neutral-density filters with optical densities as high as 4
      are designed and built in the broadband region (2-25 microm). Another key
      innovation is the use of ultrathin substrates (~100 nm thick) for elimination of
      etaloning effects normally present in thick (>0.5-mm) substrates. Neutral-density
      filters with such ultrathin substrates are also designed and investigated.

PMID- 19855565
TI  - Formation mechanism of ring domains in a TbFCo magneto-optical medium.
AB  - The formation mechanism of stable ring domains in a TbFeCo magneto-optical medium
      with compensation temperature below the ambient temperature is discussed. A ring
      domain formation model is proposed.

PMID- 19855566
TI  - High-quality self-pumped phase conjugation of nanosecond pulses at 532 nm using
      photorefractive BaTiO(3).
AB  - We implement a feedback loop oscillator, using a BaTiO(3) crystal that provides
      stable high-quality phase conjugation for nanosecond pulses, with an efficiency
      close to the theoretical maximum.

PMID- 19855567
TI  - High-gain nondegenerate two-wave mixing in Cr:YAIO(3).
AB  - A gain of 22 times was obtained by nondegenerate two-wave mixing in Cr:YAlO(3).
      To our knowledge, this is the largest cw two-wave mixing gain obtained in a bulk
      solid-state nonphotorefractive material. The measured gain appears to be limited
      by beam breakup that is due to spatial nonuniformities in the nonlinear
      refractive-index change that are the result of inhomogeneities in the crystal.
      Predictions based on our data indicate that gain in excess of 200 times should be
      possible in Cr:YAlO(3) if a homogeneous crystal can be obtained.

PMID- 19855568
TI  - Increased amplifier spacing in a soliton system with quantum-well saturable
      absorbers and spectral filtering.
AB  - The spacing between optical amplifiers in a long-haul soliton system may be
      increased to 100 km by using only passive quantum-well saturable absorbers and
      narrow-band filters for soliton control. After transmission over 9000 km at 10
      Gbits/s, the effects of soliton-soliton interaction and Gordon-Haus jitter in the
      proposed systemyield bit error rates of better than 10(-9).

PMID- 19855569
TI  - Polarization decorrelation in optical fibers with randomly varying birefringence.
AB  - Polarization decorrelation in single-mode fibers with randomly varying
      birefringence is studied. We find that decorrelation length is minimized for a
      given beat length if the average autocorrelation length of the birefringence is
      close to the average beat length. The differential time delay between the
      polarization modes is found to depend on the autocorrelation length of the
      birefringence rather than on the decorrelation length of the polarization modes.

PMID- 19855570
TI  - Frequency shifts in injection-seeded optical parametric oscillators with phase
      mismatch.
AB  - We have observed a frequency shift in the output signal pulses relative to the
      seed frequency in an injection-seeded, singly resonant, critically phase-matched,
      pulsed optical parametric oscillator in which phase mismatchwas intentionally
      introduced. The observed shifts can be large compared with the linewidth of the
      signal pulse, are approximately linear in phase mismatch, and increase with
      increasing pump fluence. We observe frequencyshifts of as much as +/-400 MHz for
      our 532-nm-pumped, potassium titanyl phosphate ring optical parametric
      oscillator. For zero phase mismatch, we observe nearly transform-limited
      linewidths of less than 130 MHz. Wecompare the experimental data to a simple
      analytic model that overestimates the shifts because it ignores pumpdepletion. We
      also compare our measurements with a numerical model that calculates the two
      dimensional, transient electric fields and the resultant spectral distributions
      while explicitly including walk-off, diffraction, and pump depletion. We find
      good agreement between the experimental data and the results of this model.

PMID- 19855571
TI  - High-average-power flash-lamp-pumped Ti:sapphire laser.
AB  - The design and free-running performance data of a high-average-power flash-lamp
      pumped Ti:sapphire laser are presented. The optimization of excitation and
      cooling of the laser crystal led to a high total efficiency of 1.9% at 220-W
      average output power. This is, to the author's knowledge, the highest output
      power reported for Ti:sapphire lasers. Diffuse reflectors with improved light
      concentration increased laser efficiency by 20%. Low thermal lensing of 0.07-D/kW
      electrical pumping power was observed.

PMID- 19855572
TI  - Efficient intracavity frequency doubling of a high-repetition-rate diode-pumped
      Nd:YAG laser.
AB  - Efficient operation of a pulsed, high-repetition-rate diode-pumped and
      intracavity frequency-doubled Nd:YAG laser is reported. A 3-mm-diameter laser rod
      was side-pumped with a 5-bar stack of high-duty-cycle 1-cm diodearrays. The
      average Q-switched power at 1.06microum was 3.8 W at 1.33 kH(z), and more than 4
      W at 0.532 ,microm wasobtained through intracavity frequency doubling with
      LiB(3)O(5).

PMID- 19855573
TI  - Laser linewidth narrowing induced by amplifier gain saturation.
AB  - We demonstrate that temporal broadening of transform-limited nanosecond pulses
      during gain saturation in a Nd:YAG amplifier can produce substantial linewidth
      narrowing. Measurements of linewidths with two-color Doppler-free saturated
      spectroscopy in I(2) show reductions in linewidth by more than a factor of 2.5
      from 58 to 20 MHz when a double-pass amplifier is used. The observed temporal
      broadening is described well by a simple gain saturation theory.

PMID- 19855574
TI  - Generation of a 45-ps-duration 15.5-nm x-ray laser.
AB  - Using a series of 100-ps optical pump pulses separated by 300 ps, we have
      produced 45-ps FWHM output pulses in neonlike yttrium operating at a wavelength
      of 15.5 nm. This is to our knowledge the shortest-pulse collisionally pumped x
      ray laser yet produced. The importance of using a traveling-wave pump to increase
      the output power is also discussed.

PMID- 19855575
TI  - Theoretical model for conversion efficiency in an intermediate singly
      resonant/doubly resonant optical parametric oscillator configuration.
AB  - A theoretical model for optical parametric oscillation (OPO) with power-dependent
      pump reflections and arbitrary idler reflectivity is presented. After the
      differential coupled-wave propagation equations under the appropriate boundary
      conditions are solved, the general expression for conversion efficiency is
      derived. The characteristic behavior of the OPO efficiency as a function of input
      pump intensity is shown to evolve from pure singly resonant oscillation to pure
      doubly resonant oscillation as the idler reflectivity is gradually varied from 0%
      to near 100%. The optimal idler reflectivity depends on the specific values of
      the given OPO components and could be found with the general results presented.

PMID- 19855576
TI  - Generation of tunable femtosecond pulses to as low as 172.7 nm by sum-frequency
      mixing in lithium triborate.
AB  - A tunable 1-kHz repetition-rate regenerative Ti:sapphire amplifier system is used
      to produce 200-fs vacuum-ultraviolet pulses in the range of 172.7-187 nm by phase
      matched sum-frequency mixing in lithium triborate of the Ti:sapphire's fourth
      harmonic and a parametrically generated infrared pulse.

PMID- 19855577
TI  - Tunable coupled-cavity waveguide laser at room temperature in Nd-diffused
      Ti:LiNbO(3).
AB  - We report on a Y-junction channel waveguide laser, operating at room temperature,
      in Nd-diffused Ti:LiNbO(3). Pumping was performed with a cw Ti:A1(2)O(3) laser
      operating at 816 nm. With feedback provided only by the polished end faces of the
      device, a cw lasing threshold of ~39-mW launched pump power was obtained, with a
      slope efficiency of ~35%. Using 95% reflectivity mirrors at the waveguide ends,
      we reduced the lasing threshold to ~4 mW, with a slope efficiency of ~2.6%.
      Tuning of the lasing signal over a range of 2.3 nm around a center wavelength of
      1092.7 nm was demonstrated, with a monolithically integrated phase modulator.

PMID- 19855578
TI  - Propagation of intense, ultrashort laser pulses in plasmas.
AB  - We have investigated the propagation of terawatt-power laser pulses in gases. The
      spatial distribution of focused radiation is modified by refraction that results
      from the spatially inhomogeneous refractive index of the plasma generated by high
      field ionization. We observe Thomson scattering, stimulated Raman scattering, and
      large wavelength shifting of the laser light.

PMID- 19855579
TI  - Nonlinear propagation of high-power, sub-100-fs pulses near the zero-dispersion
      wavelength of an optical fiber.
AB  - The propagation of high-peak-power (>10-kW) sub-100-fs pulses near the zero
      dispersion wavelength of an optical fiber was studied experimentally. Four-photon
      mixing and stimulated Raman scattering were observed for fiber lengths greater
      than 2 m. With pulses as short as 25 fs, four-photon mixing dominates, resulting
      in efficient conversion of the input pulse spectrum into two coherent spectral
      bands. This can be used to extend the useful wavelength range of femtosecond
      lasers in the infrared.

PMID- 19855580
TI  - Chirped-pulse amplification of 85-fs pulses at 250 kHz with third-order
      dispersion compensation by use of holographic transmission gratings.
AB  - We demonstrate pulse stretching and compression in a high-repetition-rate chirped
      pulse Ti:sapphire regenerative amplifier, using high-efficiency holographic
      transmission gratings. A quantitative dispersion measurement technique is
      developed to characterize dispersion of the system to the third order. After
      recompression with third-order dispersion compensation, 3.1-microJ 85-fs, nearly
      transform-limited pulses are obtained.

PMID- 19855581
TI  - Generation of synchronized, independently tunable 120-fs light pulses with
      optical parametric oscillators.
AB  - We report the generation of powerful, widely tunable femtosecond radiation by
      parallel synchronous pumping of two singly resonant optical parametric
      oscillators with an additive-pulse mode-locked Nd:glass laser. For a single-pulse
      energy of 10 nJ, a tuning range of 0.9-1.5 microm is achieved with pulse
      durations of 120 +/- 20 and 200 +/- 20 fs. The time jitter is estimated to be +/
      50 fs.

PMID- 19855582
TI  - Optimal trade-off synthetic discriminant function filters for arbitrary devices.
AB  - A new correlation-filter design methodology is presented for achieving two
      objectives: synthetic discriminant function filters that can be implemented on
      arbitrary various criteria of interest. devices and that can provide optimal
      trade-off among various criteria of interest.

PMID- 19855583
TI  - Simple procedure for the analysis of coherent imaging systems.
AB  - A simple procedure is presented for determining the Fourier-optics-regime object
      image relationship for spatially coherent wave fields in a general imaging
      system. The procedure links straightforward ray-optics methods for imaging system
      analysis with parameters of a wave-optics-based superposition kernel that
      represents the Fourier-optics aspects of the system. Standard formulas are
      presented, and several confirming examples are treated.

PMID- 19855584
TI  - Stochastic field effects and transform-limited laser pulses.
AB  - In many ultrashort-laser-pulse experiments the field is transform limited, and
      under these conditions it is usually assumed that the stochastic nature of the
      field can be ignored in the interpretation of experimental data. We theoretically
      consider the 3 + 2 photoionization of xenon, using a pulsed stochastic field. Our
      results show that the field's stochastic nature always has an effect on the ac
      Stark shift modification factor Re(M), no matter what the pulse width, and that a
      short-pulse approximation to Re(M) can require a Fourier-transform bandwidth 1000
      times larger than the laser's intrinsic (cw) spectral width.

PMID- 19855585
TI  - Observation of reflection-induced light correlation in spontaneous emission in
      front of a mirror.
AB  - We show that fluorescence spectra from a dye-doped polymer film in front of a
      mirror exhibit angular and spectral localization effects caused by self
      interference in the spontaneous emission. Experimental spectral results depending
      on film thickness are found to be by a semiclassical description. in good
      agreement with the calculated results predicted by a semiclassical description.

PMID- 19855586
TI  - Dynamical stabilization: a new model for supermolasses.
AB  - We present an analytical treatment of the force on a two-level atom interacting
      with a three-dimensional optical molasses. We show that, for small misalignment
      of the molasses light fields, corresponding to the so-called supermolasses
      configuration, there can be a dynamically induced stabilization of the atomic
      motion. This stabilization increases the time required for the atom to diffuse
      out of the molasses region and therefore provides a novel explanation of
      experimental observations. We describe the stabilization effect by analogy with
      the stabilization of the Kapitza pendulum, which is subject to a harmonic
      modulation of the pendulum pivot point.

PMID- 19855587
TI  - Simultaneous cooling and trapping of (85)Rb and (87)Rb in a magneto-optical trap.
AB  - Two different isotopes-(85)Rb and (87)Rb-have been captured simultaneously in one
      magneto-optical trap. The trap parameters could be chosen nearly independently
      for the two isotopes. The trap loss rates that are due to collisions between
      atoms of different isotopes have been measured in the low-intensity limit.

PMID- 19855588
TI  - Site-selective electronic Raman excitation spectroscopy of the lowest 4f ? 5d
      transitions in Ce(3+):Y(2)O(3).
AB  - The intensities of electronic Raman-scattering transitions between the ground
      state and the first excited state of the (2)F(7/2) manifold of Ce(3+) in both the
      C(2) and C(3i) sites of Y(2)O(3) are measured as a function of excitation
      frequency in the region of the lowest 4f ? 5d intermediate-state resonance with a
      wavelength-tunable pulsed dye laser. As the dye laser is tuned through the center
      of the resonance, we observe a 2-order-of-magnitude enhancement in electronic
      Raman-transition intensity over that for nonresonant excitation. The electronic
      Raman excitation profiles (resonance enhancement as a function of frequency) in
      the 15 949- to 23 810-cm(-1) (627-420-nm) range provide spectrally resolved
      information about the lowest 4f ? 5d transitions of both the C(2) and C(3i)
      centers that could not be obtained from the strongly overlapping absorption
      spectra.

PMID- 19855589
TI  - Holographic technique for three-dimensional three-component particle fields.
AB  - We present the preliminary results of a new technique that permits three
      dimensional three-component detection of displacing particle fields from a single
      observation direction. The technique utilizes time-sequence images independently
      reconstructed by dual-reference-beam off-axis holography. The image sections are
      then statistically correlated for displacement extraction, without the need for
      specific focusing.

PMID- 19855590
TI  - Statistical analysis of cross-talk noise and storage capacity in volume
      holographic memory.
AB  - We present a statistical analysis of cross-talk noise and consider the cross-talk
      limited storage capacity of volume holographic memory. Random-walk approximation
      is employed to estimate the intrapage interpixel cross-talk noise and the signal
      to-noise ratio. We obtain simple expressions of the storage capacity in terms of
      number of bits per volume for a given signal-to-noise ratio or bit-error rate.
      The results indicate that the storage density is reduced from the ultimate
      density of lambda(-3) by a factor related to the signal-to-noise ratio.

PMID- 19855591
TI  - Noise-free holographic storage in iron-doped lithium niobate crystals.
AB  - We show that fanning noise in lithium niobate crystals can have a deleterious
      effect on holographic storage in configurations in which the c axis and the
      grating wave vector coincide, for both ordinary and extraordinary light
      polarizations. We then demonstrate that this noise is drastically reduced when
      the c axis is perpendicular to the grating wave vector. Images have been fixed
      and read out for many hours at high intensity levels, demonstrating long-term
      storage and good-quality image recall.

PMID- 19855592
TI  - Proposed sum-and-difference method for optical-frequency measurement in the near
      infrared.
AB  - We propose a method for the determination of optical frequencies in the near
      infrared that is based on the nonlinear generation of the optical sum and
      difference frequencies of two near-infrared lasers followed by the comparison of
      the sum and difference frequencies with standards in the visible and in the far
      infrared, respectively. We also address questions of practicability and discuss
      some examples open to the method.

PMID- 19855593
TI  - Heterodyne detection technique using stimulated Brillouin scattering and a
      multimode laser.
AB  - We present, for the first time to our knowledge, the use of multiple axial laser
      modes in distributed temperature sensing based on stimulated Brillouin
      scattering. One axial mode stimulates a Stokes wave with a temperaturedependent
      Brillouin frequency shift in the 13-GHz range. Optical heterodyning of the
      stimulated Stokes wave with a second axial laser mode allows one to generate and
      evaluate a beat signal in a lower frequency range. Using diode-pumped solid-state
      lasers, we have reduced the Brillouin beat frequency to the 500-MHz range. Hence,
      low-cost detectors and conventional signal-processing techniques can be applied
      for the beat signal processing.

PMID- 19855594
TI  - Phase conjugation of an optical near field.
AB  - Using degenerate four-wave mixing in an Fe:LiNbO(3) 0.04-wt. % crystal and an
      external-reflection near-field optical microscope, we have achieved phase
      conjugation of light emitted by a fiber tip. We observe that the phase-conjugated
      light at a wavelength of 633 nm can reach a power of ~0.1 nW and produce a 180-nm
      wide spot image in the near-field microscope. This is the first direct
      demonstration, to our knowledge, of the phase conjugation of near-field
      components of optical fields.

PMID- 19855595
TI  - Light scattering by randomly oriented bispheres.
AB  - We describe how the T-matrix approach can be used to compute analytically the
      Stokes scattering matrix for randomly oriented bispheres with touching or
      separated components. Computations for randomly oriented bispheres with touching
      components are compared with those for volume-equivalent randomly oriented
      prolate spheroids with an aspect ratio of 2 and for a single volume-equivalent
      sphere. We show that cooperative (multiple-scattering) effects can make bispheres
      more efficient depolarizers than spheroids in the back-scattering direction.

PMID- 19855596
TI  - Imaging of coherent fields through lenslike systems.
AB  - I derive the imaging condition for the complex amplitude of a monochromatic field
      by a sequence of lens-like elements.

PMID- 19855597
TI  - Synthetic-array heterodyne detection: a single-element detector acts as an array.
AB  - A simple technique, synthetic-array heterodyne detection, permits an ordinary
      single-element optical detector to behave as though it were a coherent array. A
      successful experimental implementation of a synthetic two-pixel array, using a
      CO(2) laser and a single-element HgCdTe photodiode is reported. A different
      heterodyne local oscillator frequency is incident upon each resolvable region of
      the detector surface. Thus different regions are mapped to different heterodyne
      beat frequencies. One can determine where the photons struck the detector surface
      even though a single electrical connection to the detector is used. This also
      prevents the destructive interference that occurs when multiple speckles are
      imaged (akin to spatial diversity). In coherent lidar this permits a larger field
      of view. An acousto-optic modulator produces the local oscillator frequencies and
      can achieve good spatial separation of optical frequencies of the order of a
      megahertz apart.

PMID- 19855598
TI  - Spatial optical solitons governed by quadratic nonlinearity.
AB  - We demonstrate that a dielectric medium with purely quadratic nonlinearity [the
      so-called chi((2)) material] can display self-focusing phenomena through a new
      type of modulational instability of the interacting fundamental and second
      harmonic field components and therefore can support propagation of (two-wave)
      optical solitons. We prove the existence of a family of such solitons, which are
      found numerically and, in some particular cases, also analytically. The two-wave
      solitons are stable in the whole parameter region in which they exist.

PMID- 19855599
TI  - Excitation of solitons with cascaded chi((2)) nonlinearities.
AB  - Mutual trapping of the fundamental and second-harmonic waves propagating in a
      material with cascaded second-order nonlinearity is investigated. Formation of
      solitonlike waves under a variety of excitation conditions is numerically
      observed, consistent with the robustness hypothesis of solitons.

PMID- 19855600
TI  - Numerical simulations for power margins in soliton transmission systems over
      transoceanic distances.
AB  - Acceptable values for filter bandwidth and amplifier output power are determined
      by means of numerical simulations under the criteria of tolerable maximum
      standard deviation of timing jitters and minimum Q factor for fixed and sliding
      frequency in-line filters. The results, for chromatic dispersion values usually
      encountered in published experiments, represented by isojitters and iso-Q factors
      clearly show the existence of an optimum design area. From these diagrams, the
      optimum bandwidth can be obtained for the largest power margin. We also analyze
      power margins with increasing sliding rates of in-line filters. In our
      simulations we obtain a 1.5-dB power margin with fixed filters and a 3-dB power
      margin with sliding filters.

PMID- 19855601
TI  - Analysis of a directional coupler by coupled modes of a single waveguide.
AB  - Analysis of a directional coupler by use of rigorous coupled-mode theory is
      presented. The coupling process is explained by the mutual coupling of modes of a
      single waveguide that is due to the presence of the other waveguide. It is
      explicitly shown by example that the radiation modes that take part in the
      coupling are just those needed to form the guided modes of the composite double
      guide structure.

PMID- 19855602
TI  - Low-noise diode-pumped intracavity-doubled laser with off-axially cut Nd:YVO(4).
AB  - Effective noise reduction in a diode-pumped intracavity-doubled Nd:YVO(4) laser
      is achieved with a novel cavity design in which a birefringent filter is formed
      with off-axially cut Nd:YVO(4) and KTP. 20-mW green output with relative
      intensity noise of less than -120 dB/Hz was obtained under 290-mW pumping by a
      broad-area laser diode.

PMID- 19855603
TI  - 1-W average power levels and tunability from a diode-pumped 2.94-microm Er:YAG
      oscillator.
AB  - A tunable Er:YAG laser, side pumped by a quasi-cw InGaAs diode array, generates >
      500 mW of power at 2.936 microm. The cavity is a 4-cm plano-concave resonator
      that uses total internal reflection on the pump face of the Er:YAG crystal to
      couple the diode emission into the resonating modes of the oscillator. Tuning is
      accomplished by angle tuning a 300-microm-thick YAG etalon. The tuning range is
      2.933-2.939 microm. Thermal lensing limits the duty factor to 4% or 8%, depending
      on the Er:YAG crystal thickness (2 or 1 mm). A 2.5-cm-long resonator operates at
      an 11% duty factor and generates 1.3 W of average power.

PMID- 19855604
TI  - Performance of Pyrromethene 580 and 597 in a commercial Nd:YAG-pumped dye-laser
      system.
AB  - We report the performance of two new laser dyes, Pyrromethene 580 and 597, in a
      10-Hz, Nd:YAG-pumped dye-laser system. These dyes demonstrate broader and more
      efficient tuning curves compared with those of Rhodamine 590 and 610.
      Pyrromethene 580 and 597 provide peak conversion efficiencies of 38% at 552 nm
      and 32% at 571 nm, respectively. Moreover, these new dyes provide conversion
      efficiencies of 31% near 572.5 nm, a wavelength used for fluorescence studies of
      NO. This enhanced efficiency should improve the signal-to-noise ratio in linear
      fluorescence [NO] measurements.

PMID- 19855605
TI  - Improved expression for the time-bandwidth product of picosecond optical pulses
      from gain-switched semiconductor lasers.
AB  - An improved expression for the time-bandwidth product (DeltatDeltaf) of
      picosecond optical pulses from gain-switched semiconductor lasers was obtained by
      a series of numerical simulations based on rate equations without making any
      assumption for a particular pulse shape and chirp condition. The relation can be
      expressed by [Equation] as a function of the linewidth-enhancement factor alpha.
      The influence of the spontaneous emission factor beta on the relation is also
      examined.

PMID- 19855606
TI  - High-resolution spectra of cross-phase modulation in optical fibers.
AB  - Cross-phase-modulation (XPM) effects were investigated as a novel nondegenerate
      method to control the spectrum of an optical pulse. The oscillating substructures
      in the XPM spectra were measured with a high-resolution optical spectral analysis
      system. The dispersion of the third-order nonlinearity was obtained by
      measurement and analysis of the XPM and self-phase-modulation spectra of the
      probe and pump pulses at different wavelengths.

PMID- 19855607
TI  - High-repetition-rate high-power femtosecond ArF laser source.
AB  - 170-fs, 0.8-microJ optical pulses at 193 nm generated by frequency quadrupling of
      high-power Ti:sapphire laser pulses are amplified in an ArF gain module. Double
      pass amplification at a 400-Hz repetition rate resulted in 290-mW average power
      with pulse durations of ~ 300 fs.

PMID- 19855608
TI  - Highly sensitive multichannel spectrometer for subpicosecond spectroscopy in the
      midinfrared.
AB  - A spectrometer system is presented for time-resolved probing in the midinfrared
      between 5 and 11 microm with a temporal resolution of better than 400 fs.
      Multichannel detection with HgCdTe detector arrays consisting of ten elements in
      combination with a high repetition rate permits one to record weak absorbance
      changes with an accuracy of 0.1 mOD.

PMID- 19855609
TI  - Phase-coding technique for one-way image transmission through aberrating media.
AB  - We propose and demonstrate one-way image transmission through an aberrating
      medium. In contrast to previous techniques, which usually use exact phase
      compensation for correcting phase distortion, our technique uses the phase- or
      amplitude-coded form of the exact phase. This technique allows us to utilize a
      wide variety of spatial light modulators for image correction in one-way image
      transmission through aberrating media.

PMID- 19855610
TI  - Distribution of relative intensity noise in the signal and quadrature channels of
      a fiber-optic gyroscope.
AB  - We show that white optical intensity noise is in general unevenly split between
      the signal and quadrature channels of a sinusoidally modulated fiber-optic
      gyroscope. At certain modulation depths this noise is almost totally relegated to
      the quadrature channel.

PMID- 19855611
TI  - Quantized atom-field force at the surface of a microsphere.
AB  - The dipole force experienced by an atom in a nonresonant spatially inhomogeneous
      light field is quantized by the discrete nature of the photon. We propose to
      detect this quantization by studying the scattering of slow atoms that pass in
      the evanescent field of a microsphere whispering gallery mode. This constitutes
      an inverse Stern-Gerlach experiment in which the atomic deflection is correlated
      to the state of the scattering field.

PMID- 19855612
TI  - Fractional Talbot four-level phase-only holograms using ferroelectric liquid
      crystal spatial light modulators.
AB  - We propose a new technique for generating a four-level reconfigurable phase-only
      hologram, using two binary phase {0,pi} ferroelectric liquid-crystal spatial
      light modulators. The principle is based on the self-imaging properties of
      periodic structures operating in a Fresnel field double-diffraction system.
      Fractional Talbot planes are shown to be of particular interest. The problem of
      hologram bandwidth reduction that results from the holographic pattern
      replication is addressed. A trade-off between diffraction efficiency and hologram
      coding capacity is considered.

PMID- 19855614
TI  - Retroreflector with acute dihedral angles.
AB  - An acute-angle retroreflector having three dihedral angles of 45, 60, and 90 deg
      was studied by use of the ray-trace method. Incident rays are reflected nine
      times in the retroreflector, and there are 26 different sequences for
      reflections. Errors in the dihedral angles will cause the directions of the
      reflected rays to diverge. A possible application of the acute-angle
      retroreflector is in target design for laser ranging.

PMID- 19855613
TI  - High-resolution surface-emitting spectrometer and deformation sensors with
      nonlinear waveguides.
AB  - We investigate the limits of frequency resolution attainable in a nonlinear
      waveguide optical spectrometer, including the effects that are due to surface
      distortions and waveguide inhomogeneities, and demonstrate that the frequency
      resolving capability is directly scalable with the radiating aperture length. The
      resolution of the waveguide is diffraction limited, and therefore the far-field
      radiation pattern can be used to characterize the phase variations along the
      waveguide that are due to surface distortions. The use of this device as a highly
      sensitive deformation sensor is demonstrated by application of a distortion to
      the waveguide and confirmation of the far-field diffraction pattern generated.

PMID- 19855615
TI  - Dielectric polarizability of a sphere with arbitrary anisotropy: comment.
AB  - Sihvola's observation [Sihvola, Opt. Lett. 19, 430 (1994)] of an analogy between
      various elements of the polarizability dyadics for anisotropic spheres and the
      polarizabilities of chiral spheres is critically examined. It is argued that this
      analogy is both physically and mathematically misconceived.

PMID- 19855616
TI  - Dielectric polarizability of a sphere with arbitrary anisotropy: reply to
      comment.
AB  - This reply attempts to cast some more light on the problematic similarities and
      differences between gyrotropic and chiral materials.

PMID- 19855617
TI  - Normalized expressions for the optical sensitivity of evanescent wave sensors:
      erratum.

PMID- 19855618
TI  - Effective-medium predictions of absorption by graphitic carbon in water droplets.
AB  - Effective medium theories are valuable tools that can provide effective
      refractive indices of composite media whose constituents are much smaller than
      the wavelength of the illuminating radiation. Extended theories have been
      developed to remove this limitation on the constituent size. Although these
      extended theories are not derived without additional limitations, useful regions
      of applicability do exist. We examine an extended effective-medium approximation
      and show that its predicted absorption efficiencies obtained agree well with
      exact theoretical results obtained for a naturally occurring system of interest,
      water droplets containing carbon inclusions.

PMID- 19855619
TI  - Fractional Fourier transform as a tool for analyzing beam propagation and
      spherical mirror resonators.
AB  - The complex amplitude distributions on two spherical reference surfaces of given
      curvature and spacing are simply related by a fractional Fourier transform. The
      order of the fractional Fourier transform is proportional to the Gouy phase shift
      between the two surfaces. This result provides new insight into wave propagation
      and spherical mirror resonators as well as the possibility of exploiting the
      fractional Fourier transform as a mathematical tool in analyzing such systems.

PMID- 19855620
TI  - Laser-induced thermal grating effects in flames.
AB  - Light scattering from a laser-induced thermal grating produced in an atmospheric
      pressure H(2)/O(2) flame is observed with a phase-matching geometry commonly used
      in resonant four-wave mixing and laser-induced grating spectroscopy. The presence
      of thermal gratings is confirmed in both the time and the frequency domains in
      two distinct experiments. Diluting the flame with helium decreases the thermal
      grating signal intensity. Experimental results agree well with calculations based
      on a solution of the linearized hydrodynamic equations.

PMID- 19855621
TI  - Photomechanical basis of laser ablation of biological tissue.
AB  - The photomechanical model of laser ablation of biological tissue asserts that
      ablation is initiated when the laser-induced tensile stress exceeds the ultimate
      tensile strength of the target. We show that, unlike the one-dimensional
      thermoelastic model of laser-induced stress generation that has appeared in the
      literature, the full three-dimensional solution predicts the development of
      significant tensile stresses on the surface of the target, precisely where
      ablation is observed to occur. An interferometric technique has been developed to
      measure the time-dependent thermoelastic expansion, and the results for
      subthreshold laser fluences are in precise agreement with the predictions of the
      three-dimensional model.

PMID- 19855622
TI  - Diffractive optics: the gradial zone lens.
AB  - A gradial zone lens has the diffractive component within the bulk lens rather
      than as a surface-relief profile. It is constructed by spin molding annular zones
      from microliter volumes of monomers injected into a rotating mold. Plastic lenses
      have micrometer width zones with dimensions that give a phase difference of
      modulo 2pi. A gradial lens made with flat surfaces shows a series of foci similar
      to those of a radially blazed grating; however, when zones are placed within a
      plano-convex lens, there is an additive contribution from both refractive and
      diffractive focusing.

PMID- 19855623
TI  - Determination of the phase change on reflection from two-beam interference.
AB  - Light reflected by a nondielectric material experiences a phase change on
      reflection that differs from light reflected by a dielectric material and other
      nondielectric materials. The complex degree of coherence for small optical path
      differences is derived for two-beam interference when the illumination source is
      extended, incoherent, and quasi-monochromatic. An analysis of the two-beam
      interference pattern reveals a simple relationship between the phase of the
      interference pattern at the point of maximum fringe visibility and the material
      dependent phase change on reflection.

PMID- 19855624
TI  - Q spoiling and directionality in deformed ring cavities.
AB  - A ray-optics model is developed to describe the spoiling of the high-Q
      (whispering gallery) modes of ring-shaped cavities as they are deformed from
      perfect circularity. A sharp threshold is found for the onset of Q spoiling as
      predicted by the Kolmogorov-Arnol'd-Moser (KAM) theorem of nonlinear dynamics.
      Beyond the critical deformation b(c), Q ~ (b - b(c))(-alpha), alpha
      asymptotically equal to 2.4-2.6. The escaping light emerges in certain specific
      directions, which may be predicted.

PMID- 19855625
TI  - Geometrical threshold zones and Gaussian modes in lasers with radially varying
      gain.
AB  - The effect of a radially varying gain in tightly focused lasers is investigated
      with a generalized ABCD matrix formalism in a nonparabolic approximation. It is
      shown that the beam sizes can differ strongly from the theoretical with a
      constant gain or with radially varying gain in a parabolic approximation.
      Geometrical threshold zones are defined and studied and, instead of the stability
      zones, determine the possibility of a laser action for a given cavity design.

PMID- 19855626
TI  - Measurement and origin of magnetostrictive noise limitation in magnetic fiber
      optic sensors.
AB  - Fiber-optic magnetic sensors based on magnetostriction yield l/f-type noise,
      which has typically been limiting the sensors' resolution at frequencies below 1
      Hz. To study the origin of this noise, we devised a new experimental technique
      that discriminates between the transducer self-noise and various other noise
      sources and determines under which conditions the limiting noise source is the
      material's self-noise.

PMID- 19855627
TI  - Photorefractive response time measurement in GaAs crystals by phase modulation in
      two-wave mixing.
AB  - We describe a new method for photorefractive response time measurement in fast
      photorefractive crystals based on continuous phase modulation in two-wave mixing.
      We report experimental results for undoped semi-insulating GaAs that are in good
      agreement with theory. Values obtained for the response time and photoelectron
      generation quantum efficiency are consistent with previously published data.

PMID- 19855628
TI  - Recovery of the soliton self-frequency shift by optical phase conjugation.
AB  - The recovery of the self-frequency shift effect on a soliton by optical phase
      conjugation is investigated. It is proved that, without third-order dispersion
      and fiber loss, the soliton self-frequency shift can be completely recovered. The
      recoveries for a fundamental soliton and a second-order soliton in the presence
      of third-order dispersion and of fiber loss, which is compensated by the
      distributed erbium-doped fiber amplifiers, are numerically studied.

PMID- 19855629
TI  - Antiresonant ring interferometric nonlinear spectroscopy for nonlinear-optical
      measurements.
AB  - We describe a sensitive and simple single-beam technique to measure
      simultaneously the real and the imaginary contributions to the complex optical
      nonlinearity (the nonlinear refraction and absorption). We call this technique
      antiresonant ring interferometric nonlinear spectroscopy (ARINS). An antiresonant
      ring interferometer, which has improved stability, is used to detect very small
      changes in the phase and the amplitude of an optical beam. This allows very low
      intensities to be used and eliminates many interfering processes present in other
      techniques that require higher intensities. We demonstrate ARINS by measuring the
      optical nonlinearities of bulk ZnS, KDP, and C(70) thin films.

PMID- 19855630
TI  - All-optical switching by means of collisions of spatial vector solitons.
AB  - The collisions of spatial vector solitons have been investigated numerically.
      Both the polarization and propagation directions of the solitons are changed
      after collision, which could be useful in the applications of all-optical
      switching. It is also found that both the polarization mixing and the beam
      deflection become exponentially smaller as theta increases. The advantages of
      using vector solitons in optical switching are discussed.

PMID- 19855631
TI  - Compression, self-bending, and collapse of Gaussian beams in photorefractive
      crystals.
AB  - By means of an exact solution, we demonstrate that a Gaussian beam can undergo
      spatial compression when it traverses a photorefractive medium. This is possible
      provided that the external bias field exceeds the critical value necessary to
      establish photorefractive spatial solitons. In this regime and under paraxial
      assumptions our analysis indicates that a Gaussian beam tends to exhibit self
      focusing collapse. Beam self-deflection effects that arise from the pi/2-phase
      shifted component of the photorefractive grating are also considered in our
      study.

PMID- 19855632
TI  - Multidimensional solitons in cubic nonlinear media.
AB  - We show numerically that, contrary to what has been believed so far,
      multidimensional optical solitons can propagate in cubic nonlinear media. To
      avoid a collapse along the propagation axis, we take advantage of the cross-phase
      modulations between fundamental- and harmonic-field components. A compact
      analytical expression for new solitonlike fields with an arbitrary transverse
      dimension is derived through a self-consistent-field approximation.

PMID- 19855633
TI  - All-optical processing by means of vectorial interactions in second-order
      cascading: novel approaches.
AB  - Based on the tensorial nature of second-order nonlinear susceptibilities, we show
      how two orthogonal field components at frequency omega can interact by means of
      the generated second harmonic, with a resulting coherent control of one onto the
      other. All-optical transistor operation and polarization switching are among the
      signal functions that can be implemented in properly oriented crystals.

PMID- 19855634
TI  - Observation of orientational photorefractive effects in nematic liquid crystals.
AB  - We report the observation of nonlinear photorefraction in pure aligned nematic
      liquid crystals in the presence of an applied dc electric field. The effect is
      attributed to nematic axis reorientation created by the photoinduced space-charge
      field in combination with the applied dc field. Strong optical nonlinearity, self
      diffraction, and beam-coupling effects are observed.

PMID- 19855635
TI  - Two-photon-resonant photoinduced second-harmonic generation in Er(3+)-doped
      germano-aluminosilicate optical fibers pumped at 1.319 microm.
AB  - The growth of a two-photon-resonant photoinduced second-harmonic signal at 660 nm
      in Er(3+)-doped GeO(2)-Al(2)O(3)-SiO(2) single-mode optical fibers pumped by a
      Nd:YAG laser at 1.319 microm is reported. Defect states in the band gap are
      optically excited through a resonant two-photon absorption process connecting the
      (4)I(15/2)-(4)F(9/2) energy levels of the erbium ions present in the fiber core.
      As a result a periodic X((2)) grating is formed, and efficient second-harmonic
      generation takes place. For erbium-free GeO(2)-doped silica test fibers no second
      harmonic signal has been detected, even after hours of seeded preparation
      process.

PMID- 19855636
TI  - Correction of phase and depolarization distortions in a multimode fiber at 1.064
      microm with stimulated-Brillouin-scattering phase conjugation.
AB  - We have used phase conjugation to compensate phase distortions and depolarization
      introduced in multimode fibers having 2-m lengths and 400-microm core diameters.
      The experiment was performed at a wavelength of 1.064 microm, and we achieved
      phase conjugation using Brillouin-enhanced four-wave mixing in a 0.8-mm-core
      hollow quartz lightguide filled with TiCl(4). The far-field conjugation fidelity
      was 70%, and the residual depolarization was <1%. Comparable compensation was
      achieved by use of either a graded-index or a step-index fiber.

PMID- 19855637
TI  - Periodically segmented waveguides in Ti:LiNbO(3).
AB  - Periodically segmented waveguides with periods of few tens of micrometers and
      nonconnected segments are studied experimentally in Ti:LiNbO(3). The near-field
      patterns were found to expand with decreasing duty cycle but to be independent of
      the segmentation period. The measured segmentation losses vary between 0.5 and
      2.5 dB/cm, depending on the period and the duty cycle. These results agree with a
      simple numerical model, based on two loss mechanisms: waveguide segmentation and
      surface relief related to Ti indiffusion.

PMID- 19855638
TI  - Continuous-wave singly resonant pump-enhanced type II LiB(3)O(5) optical
      parametric oscillator.
AB  - We report what is to our knowledge the first demonstration of a pump-enhanced
      singly resonant continuous-wave optical parametric oscillator. The nonlinear
      material used was lithium triborate cut for noncritical phase matching along the
      z axis, and the device was pumped by a single-frequency argon-ion laser. The
      oscillation threshold was ~1.0 W at 514.5 nm. For 3.4 W of pump power, we
      obtained single-frequency output powers of 500 mW in the nonresonant wave, which
      we temperature tuned over 14 nm.

PMID- 19855640
TI  - Tunable, narrow-linewidth output from an injection-locked high-power AlGaAs laser
      diode array.
AB  - An injection-locking technique has been employed to produce single-frequency
      tunable output from a high-power AlGaAs laser diode array. A narrow-linewidth
      external cavity laser is used as a master oscillator. With an injected power of
      15 mW, a total output power of 1.0 W was obtained from the laser diode array with
      a spectral linewidth of less than 38 kHz, a wavelength tuning range of 13 nm, and
      a 0.67 degrees -wide single-lobed far-field beam.

PMID- 19855639
TI  - Two-dimensional Er:YSGG microlaser array pumped with a monolithic two-dimensional
      laser diode array.
AB  - We have demonstrated one- and two-dimensional Er:YSGG microlaser arrays at 2.8
      microm output wavelength with power levels up to 900 mW cw. The one-dimensional
      microlaser arrays are based on conventional edge-emitting laser diodes, and the
      two-dimensional microlaser arrays are based on surface-emitting monolithic two
      dimensional laser diode arrays with 45-deg deflectors.

PMID- 19855641
TI  - Semiconductor lasers without population inversion.
AB  - We propose a new scheme for lasing without population inversion that utilizes
      interferences in double-quantum-well intersubband transitions. In contrast to the
      previous inversionless laser schemes based on atomic systems, the new proposal
      permits us to use band-gap engineering to choose the subband energies, coupling
      strengths, and decay rates, as desired, and permits us to create a laser system
      that does not require population inversion. We present detailed calculations on a
      specific scheme and discuss possible extensions.

PMID- 19855642
TI  - Additive-pulse mode-locking/limiting storage ring.
AB  - A pulse-storage ring is an optical device capable of memorizing a pulse sequence
      of 0's and l's. The soliton ring of Nakazawa et al. [Electron. Lett. 29, 729
      (1993)] with nearly unlimited transmission distance is such a device. We propose
      and experimentally demonstrate a different type of pulse-storage ring that uses
      intensity-dependent interferometric action to create a stronger intracavity
      transmission differential between the 0's and the l's.

PMID- 19855643
TI  - Third-order dispersion in femtosecond fiber lasers.
AB  - We experimentally investigate the effects of third-order dispersion (TOD) on
      ultrafast sources, using dispersion-compensated femtosecond fiber lasers. By in
      situ measurement of the intracavity dispersion, we identify spectral resonances
      that are due to coupling of the cavity pulse energy to dispersive wave components
      at the phase velocity and group-velocity-matched wavelengths. We obtain pulse
      widths as short as 91 fs by partially compensating the TOD. We relate the
      observed effects to consequences for soliton transmission and operation of other
      solitary-pulse lasers.

PMID- 19855644
TI  - Parametric oscillation and compression in KTP crystals.
AB  - We report effective pulse compression under conditions of giant-pulse generation
      in a synchronously pumped parametric oscillator pumped by the second-harmonic
      radiation of an actively-passively mode-locked Nd;YAG laser with passive negative
      feedback. A minimum pulse duration of 0.39 ps is achieved. The output radiation
      can be tuned from 0.614 to 4.16 microm.

PMID- 19855645
TI  - Compact dispersion-compensating geometry for Kerr-lens mode-locked femtosecond
      lasers.
AB  - We demonstrate a new technique for dispersion compensation in Kerr-lens mode
      locked (KLM) lasers that uses a novel resonator design in conjunction with a
      prismatic end mirror. This approach achieves intracavity dispersion compensation
      without the need for prism pairs or dispersion-compensating mirrors. A pulse
      repetition rate of 1 GHz, to our knowledge the highest repetition rate achieved
      in a KLM laser to data, is generated with a pulse durations of 111 fs. Pulse
      durations of 54 fs are achieved at a repetition rate of 385 MHz. We believe that
      this new dispersion-compensation technique will be useful for the development of
      compact femtosecond sources.

PMID- 19855647
TI  - Implementation of the arbitrary free-space optical interconnections with equal
      path lengths by use of a layered structure.
AB  - We describe and demonstrate a scheme to implement arbitrary space-variant optical
      interconnections with equal path lengths in free-space, using a layered structure
      for a low gate count and high throughput. We discuss extending the technique to
      reduce the number of layers by performing small group interconnections on
      laterally separable locations.

PMID- 19855646
TI  - Optical complex matrix-vector multiplication with negative binary inner products.
AB  - Based on the mixed negative binary number system, we propose an inner-product
      algorithm for digital complex-valued matrix-vector multiplication. The features
      are no carries, no signs, no indications for decimal points, and simple
      preprocessing and postprocessing. Correspondingly, an optical architecture of
      incoherent optical correlation with spatial digital coding of data is suggested.
      Negative binary complex matrix-vector multiplication can be realized optically in
      parallel with a high accuracy. The experimental result is also given.

PMID- 19855648
TI  - Optical correlator that uses cesium vapor.
AB  - We obtain the correlation pattern between two amplitude-modulated input images of
      36 and 280 random black and white pixels, using the standard degenerate four-wave
      mixing geometry of 852-nm optical beams in a 1-mm-thick cesium-vapor cell. The
      total optical input power is 3.2 mW to obtain 0.4 nW of power in the correlation
      pattern. We verified that the buildup time of the four-wave-mixing signal is ~30
      ns. Using the random patterns, we analyze the performance of the cesium optical
      correlator in terms of the number of pixels that can be processed and the number
      of photons per pixel used. We show how to scale our experimental results for the
      efficiency of the cesium correlator to images containing a larger number of
      pixels.

PMID- 19855649
TI  - Anisotropic velocity-dependent vortex forces: two-level atoms in two-dimensional
      standing waves.
AB  - We consider the velocity-dependent light pressure force on a two-level atom
      interacting with a two-dimensional nearly resonant standing-wave light field. We
      show that there can be anisotropic cooling-heating forces that will cool the
      atoms along one field axis while heating them along the perpendicular axis. The
      force is identified as a spontaneous vortex force associated with the local
      traveling-wave character of the two-dimensional field. We provide a simple
      interpretation of this anomalous force in terms of the interplay between the
      vortical momentum flow of the light field and a motion-induced population
      transfer between the ground and excited atomic states.

PMID- 19855650
TI  - Measurements of the probability distribution of the phase difference between two
      quantum fields.
AB  - We have measured the probability distribution of the phase difference Phi(2) -
      Phi(1) between two signal fields produced by parametric downconversion from two
      cascaded nonlinear crystals for several different values of the degree of mutual
      coherence. The experimental results are compared with theory, based on our
      operational approach to phase operators for quantum fields, and good agreement is
      obtained. These results are of interest because they constitute what we believe
      is the first experimental test of our phase theory for nonclassical states of
      light.

PMID- 19855651
TI  - Cross talk for angle- and wavelength-multiplexed image plane holograms.
AB  - The cross talk for image plane holograms is calculated and compared with
      previously derived results for Fourier plane holograms. Image plane storage is
      found to have significantly smaller cross talk.

PMID- 19855652
TI  - Delivering the same optical frequency at two places: accurate cancellation of
      phase noise introduced by an optical fiber or other time-varying path.
AB  - Although a single-mode optical fiber is a convenient and efficient
      interface/connecting medium, it introduces phase-noise modulation, which corrupts
      high-precision frequency-based applications by broadening the spectrum toward the
      kilohertz domain. We describe a simple double-pass fiber noise measurement and
      control system, which is demonstrated to provide millihertz accuracy of noise
      cancellation.

PMID- 19855653
TI  - High-optical-isolation low-loss moderate-switching-speed nematic liquid-crystal
      optical switch.
AB  - A bulk polarization-rotation-based 1 x 2 optical switch is demonstrated by use of
      a birefringent-mode parallel-rub nematic liquid-crystal cell and a calcite
      Thompson-prism polarizing beam splitter. With 633-nm linearly polarized light the
      switch output ports exhibit a >36-dB optical isolation with less than -0.75 dB of
      optical insertion loss. A >1.5-ms switching speed is demonstrated for a cascade
      cell optical arrangement by means of the transient nematic effect with >30 dB of
      optical isolation and -1.45 dB of optical loss.

PMID- 19855654
TI  - Group-velocity dispersion in an all-pass Bragg filter.
AB  - On the basis of previously performed theoretical analysis it is shown that a
      slanted volume grating acts as an all-pass filter with nonlinear dispersion when
      the diffracted wave is evanescent. An analytical expression for the grating
      transfer function applicable over a wide angular range of mutual orientation of
      the initial wave and grating vectors is presented. It is demonstrated that group
      velocity dispersion (GVD) in an all-pass Bragg filter is a frequency-dependent
      quasi-periodic function provided that GVD levels are sufficiently high.

PMID- 19855655
TI  - Si/B(4)C narrow-bandpass mirrors for the extreme ultraviolet.
AB  - We report the results of extreme-ultraviolet reflectance measurements and
      structural characterization of multilayer mirrors made by sequential sputter
      deposition of Si and B(4)C. Compared with Si/Mo multilayers, Si/B(4)C have a much
      narrower bandpass (deltalambda) and better off-peak rejection but lower peak
      reflectance (R(0)). Mirrors with three different designs gave the following
      results: R(0) = 0.275 and deltalambda = 0.31 nm at 13.1 nm and normal incidence;
      R(0) = 0.34 and deltalambda = 1.1 nm at 18.2 nm and 45 degrees ; and R(0) = 0.30
      and deltalambda = 2.0 nm at 23.6 nm and 45 degrees . These multilayers exhibited
      excellent stability on annealing at temperatures up to 600 degrees C.

PMID- 19855656
TI  - Optical switching in lambda/4-shifted nonlinear periodic structures.
AB  - We show that lambda/4-shifted distributed-feedback nonlinear devices can be used
      as an all-optical switch at relatively low input intensities. The lambda/4 shift
      opens a narrow transmission window whose peak position within the stop band
      depends on the input intensity, a feature that can be used for low-power optical
      switching. The nonlinear coupled-mode approach is used to analyze the stationary
      operating regime of such a device and determine the transmittivity as a function
      of the input intensity. A closed-form solution, rather than a numerical one, is
      found for what we believe is the first time.

PMID- 19855658
TI  - Optical operations on wave functions as the Abelian subgroups of the special
      affine Fourier transformation.

PMID- 19855657
TI  - Biphoton holographic storage in Methyl Orange and Ethyl Orange dyes: erratum.

PMID- 19855659
TI  - Evaluation of the optical characteristics of the Schwarzschild x-ray objective.

PMID- 19855661
TI  - Er3+-doped fiber ring laser for gyroscope application.

PMID- 19855660
TI  - Optical trapping of microscopic metal particles.

PMID- 19855662
TI  - Upconverting time gate for imaging through highly scattering media.

PMID- 19855663
TI  - Nonlinear rotation of three-dimensional dark spatial solitons in a Gaussian laser
      beam.

PMID- 19855664
TI  - Measurement of the linear electro-optic coefficient in poled amorphous silica.

PMID- 19855665
TI  - Optical trap activation in a photorefractive polymer.

PMID- 19855666
TI  - Polarization spatial chaos in second-harmonic generation.

PMID- 19855667
TI  - Second-harmonic generation in absorptive media.

PMID- 19855668
TI  - Noise figure of upconversion-pumped erbium-doped fiber amplifiers: theory.

PMID- 19855669
TI  - Wave-front processing through integrated fiber optics.

PMID- 19855671
TI  - Laser ablation of nonlinear-optical polymers to define low- loss optical channel
      waveguides.

PMID- 19855670
TI  - Frequency-domain interferometer for measurements of the polarization mode
      dispersion in single-mode optical fibers.

PMID- 19855672
TI  - Silver halide midinfrared optical fiber Y coupler.

PMID- 19855673
TI  - Computer simulation of an optically pumped 385-[mgr ]m D2O laser based on the
      semiclassical laser theory.

PMID- 19855675
TI  - Wavelength shifts of a suspended-single-droplet dye laser by successive laser
      pumping.

PMID- 19855674
TI  - Passively Q-switched Nd-doped waveguide laser.

PMID- 19855676
TI  - Widely tunable femtosecond optical parametric amplifier at 250 kHz with a
      Ti:sapphire regenerative amplifier.

PMID- 19855677
TI  - Hybrid mode locking of a flash-lamp-pumped Ti:Al2O3 laser.

PMID- 19855678
TI  - High-repetition-rate diode-pumped Nd:YVO4 slab laser.

PMID- 19855679
TI  - All-solid-state self-mode-locked Ti:sapphire laser.

PMID- 19855680
TI  - Interferometric observation of femtosecond free induction decay.

PMID- 19855681
TI  - Subfemtosecond pulses.

PMID- 19855682
TI  - Numerical simulation of subpicosecond soliton formation in a nonlinear coupler
      laser.

PMID- 19855684
TI  - Holographic contouring by using tunable lasers.

PMID- 19855683
TI  - Hybrid grating - prism stretcher - compressor system with cubic phase and
      wavelength tunability and decreased alignment sensitivity.

PMID- 19855685
TI  - Linear image differentiation by use of analog differential self-electro-optic
      effect devices.

PMID- 19855686
TI  - C2HD and 13C2H2 absorption lines near 1530 nm for semi-conductor-laser frequency
      locking.

PMID- 19855688
TI  - Precision measurements of the lifetime of a single trapped ion with a nonlinear
      electro-optic switch.

PMID- 19855687
TI  - Observation of a single atom in a magneto-optical trap.

PMID- 19855689
TI  - Dynamic phase-encoding storage of 64 images in a BaTiO3 photorefractive crystal.

PMID- 19855690
TI  - One-step technique for enlarging straddling holographic images by white-light
      projection onto a diffractive screen.

PMID- 19855692
TI  - Faraday effect current sensor with improved sensitivity - bandwidth product.

PMID- 19855691
TI  - Multiplexed diode-laser sensor system for simultaneous H2O, O2, and temperature
      measurements.

PMID- 19855693
TI  - Direct-view fiber-optic confocal microscope.

PMID- 19855694
TI  - Contribution of the 2 1Ag state to the third-order optical nonlinearity in a
      squaraine dye: errata.

PMID- 19855695
TI  - Scanning microscopy through thick layers based on linear correlation.
AB  - Scanning microscopy in combination with an interferometric correlation technique
      that uses short light pulses or broadband cw light is shown to permit enhanced
      depth discrimination, which is particularly useful for imaging through thick
      layers introducing spherical aberration and through scattering media.

PMID- 19855696
TI  - Spectral and temporal measurements of laser action of Rhodamine 640 dye in
      strongly scattering media.
AB  - Laser action of Rhodamine 640 perchlorate in highly scattering media consisting
      of TiO(2) nanoparticles in methanol pumped by a 3-ns 532-nm laser pulse is
      observed by use of spectral and temporal measurements. The threshold for
      stimulated emission is dependent on the concentration of both laser dye and
      scattering particles. For a 2.5 x 10(-2) M dye concentration, the lasing
      threshold was found to be reduced by more than 2 orders of magnitude when the
      density of scattering particles was increased from 5 x 10(9) to 2.5 x 10(12) cm(
      3). However, for a concentration of 5 x 10(-4) M of Rhodamine 640 the lasing
      threshold was higher in scattering media than for the methanol host. The pulse
      duration of stimulated emission for Rhodamine 640 perchlorate in these random
      systems is ~50 ps.

PMID- 19855697
TI  - Strong optical asymmetry of an interference wedge with unequal-reflectivity
      mirrors and its use in unidirectional ring laser designs.
AB  - On the basis of theory and experiment we discuss the strong optical asymmetry in
      reflection exhibited by an interference wedge when it is constructed of unequal
      reflectivity mirrors and show how this feature can be used to develop attractive
      unidirectional ring lasers. In the proposed ring cavity schemes a single
      interference wedge is employed simultaneously as a tuning element, as an element
      introducing asymmetry, and as a laser output coupler.

PMID- 19855698
TI  - Origin of phosphorescence signals reemitted from tissues.
AB  - We investigate the origin of fluorescent or phosphorescent signals reemitted from
      highly scattering media (such as tissues), using diffusion theory and probability
      analysis. Results show that the lifetime of a uniformly distributed
      phosphorescent or fluorescent optical probe will profoundly affect the volume
      interrogated by noninvasive reflectance measurements. When the lifetime is
      greater than photon migration times, the origin of the reemitted signal is
      confined closest to the surface. Our computations suggest that noninvasive
      measurements of tissue oxygen concentration may not necessarily interrogate deep
      tissues when systemically administered phosphorescent dyes are used.

PMID- 19855699
TI  - Control of spatial excitation patterns in two-level systems by use of time-domain
      fields.
AB  - Spatial structures created by pulsed field interactions with surface-bound two
      level systems are considered. Superresolved pattern formation is possible by the
      use of extra degrees of freedom programmed in the time-domain field.

PMID- 19855700
TI  - Portable, high-bandwidth frequency-domain photon migration instrument for tissue
      spectroscopy.
AB  - We describe a novel frequency-domain photon migration instrument employing direct
      diode laser modulation and avalanche photodiode detection, which is capable of
      noninvasively determinating the optical properties of biological tissues in near
      real time. An infinite medium diffusion model was used to extract absorption and
      transport scattering coefficients from 300-kHz to 800-MHz photon-density wave
      phase data. Optical properties measured in tissue-simulating solutions at 670 nm
      agreed to within 10% of those expected.

PMID- 19855701
TI  - Mode properties of a plasma waveguide for intense laser pulses.
AB  - A recently demonstrated plasma light pipe [Phys. Rev. Lett. 71, 2142 (1993)] is
      shown to support single-mode, multimode, and leaky-mode propagation at
      intensities as high as 10(14)W/cm(2). The conditions that determine these
      propagation regimes are elaborated.

PMID- 19855702
TI  - Equivalent field of paraxial diffraction of a zone plate.
AB  - A simplified way is proposed to compute the paraxial diffraction of a zone plate.
      The complicated diffraction field is approximated by an equivalent field, which
      is the diffraction field of a hole weighted by the area. Based on this equivalent
      expression of the diffraction field, a graphic method is applied to calculate the
      resolving power of a zone plate. The result is consistent with those reported in
      earlier publications [Am. J. Phys. 19, 359 (1951); J. Opt. Soc. Am. 57, 610
      (1967)].

PMID- 19855703
TI  - Asymmetric spatial soliton dragging.
AB  - A new low-latency, cascadable optical logic gate with gain, high contrast, and
      three-terminal input-output isolation is introduced. The interaction between two
      orthogonally polarized spatial solitons brought into coincidence at the boundary
      of a saturating nonlinear medium and propagating in different directions results
      in the phase-insensitive spatial dragging of a strong pump soliton by a weaker
      signal. As a result, the strong pump is transmitted through an aperture when the
      weak signal is not present, and it is dragged to the side by more than a beam
      width and blocked in the presence of the weak signal, thus implementing an
      inverter with gain. A multi-input, logically complete NOR gate also can be
      implemented in a cascaded system.

PMID- 19855704
TI  - Dislocation density-dependent photorefractive effect in (001)-cut GaAs.
AB  - We present studies of the photorefractive effect in nonphotorefractive
      orientations of liquid-encapsulated Czochralski-grown GaAs crystals. Picosecond
      diffraction experiments conducted in different samples show that a forbidden
      photorefractive signal correlates well with dislocation density, which points out
      that the effect arises from strain fields and growth defects.

PMID- 19855705
TI  - Direct measurement of cascaded nonlinearity in lithium niobate channel
      waveguides.
AB  - We report on interferometric measurements of nonlinear phase shifts of the
      fundamental mode that are due to cascading in a second-harmonic-generation
      experiment in lithium niobate channel waveguides. With temperature tuning of the
      wave-vector mismatch the nonlinear phase shifts were adjustable in sign and
      magnitude. Varying the wave-vector matching condition along the waveguide leads
      to large phase shifts with low depletion and dispersion of the fundamental.

PMID- 19855706
TI  - Frequency doubling of 100-fs pulses with 50% efficiency by use of a resonant
      enhancement cavity.
AB  - The use of a resonant cavity for efficient second-harmonic generation with 100-fs
      pulses is demonstrated. With 2-nJ pulses from a mode-locked Cr:forsterite laser,
      53% conversion efficiency to the second harmonic at 625 nm is achieved while ~100
      fs duration is maintained. This is an order-of-magnitude improvement over the
      conversion efficiency obtained directly with the laser output.

PMID- 19855707
TI  - Near-infrared continuum generation with upconversion into the visible in SiO(2)
      single-mode fiber.
AB  - The conditions leading to the recent observation of efficient upconversion of
      1319-nm radiation to 580 nm in SiO(2) single-mode fiber are examined. Simulation
      results, based on the third-order nonlinearity and the waveguiding
      characteristics of typical fiber, show that the visible signal may be generated
      by phase-matched four-wave mixing within the concurrently generated infrared
      spectral continuum.

PMID- 19855708
TI  - Asynchronous soliton mode locking.
AB  - We report a harmonically mode-locked erbium-doped fiber ring laser with short
      solitons. A phase modulator running asynchronously with the pulses provides pulse
      start-up, continuous background cleanup, and a new form of pulse timing
      stabilization. Steady-state operation of picosecond solitons at a repetition rate
      of 1 GHz was obtained with no need for modulator drive frequency stabilization.

PMID- 19855709
TI  - Measurement of ultraviolet subpicosecond pulses based on ultrafast beam
      deflection.
AB  - We describe a beam-deflection technique based on the ultrafast electronic Kerr
      effect for measuring the duration of ultrashort laser pulses in a wide spectral
      range. Using this method, which provides the third-order intensity correlation
      function, we have measured subpicosecond KrF laser pulses. The results are in
      good agreement with the Kerr-shutter autocorrelation measurement.

PMID- 19855710
TI  - Four-port fiber frequency shifter with a null taper coupler.
AB  - A prototype of a new design of fiber frequency shifter, based on a special four
      port fused taper coupler with a null maximum coupling ratio, is reported. In this
      coupler the constituent fibers are so dissimilar that the maximum coupling is
      (ideally) zero. In the presence of a flexural acoustic wave, light is coupled
      between the fibers, acquiring a frequency shift in the process. Near 100%
      conversion with 30-dB sideband and carrier suppression is achieved, in an
      unoptimized device, for just 1 mW of electrical drive power.

PMID- 19855711
TI  - Frequency upconversion by phase-matched sum-frequency generation in an optical
      parametric oscillator.
AB  - We report the generation of 0.589-,microm radiation from mixing the pump at 1.064
      ,microm and the signal at 1.319 microm of a singly resonant, synchronously pumped
      AgGaS(2) optical parametric oscillator. A KTP crystal is used for the sum
      frequency generation (SFG). Both extracavity and intracavity SFG is demonstrated,
      with overall conversion efficiencies of 3.5% and 10.5%, respectively. Near
      transform-limited pulses of less than 50 ps are generated from 100-ps pulses.
      With a limited available peak pump power, both spatial orderings of the KTP and
      the AgGaS(2) crystals for intracavity SFG produce similar conversion efficiency
      and outputs of similar pulse duration, spectral width, and stability.

PMID- 19855712
TI  - Feedback-induced polarization switching in a Nd-doped fiber laser.
AB  - We demonstrate a switching effect between the two polarization eigenstates of a
      Nd-doped fiber laser when it is subjected to an optical feedback signal.
      Conditions for an optimization of this effect are recognized to depend on the
      relative orientation of the fiber eigenaxes and the polarization states of the
      pump and feedback beams.

PMID- 19855714
TI  - High modal discrimination in a Nd:YAG laser resonator with internal phase
      gratings.
AB  - A unique laser resonator containing an internal phase grating and a diffractive
      mode-selecting mirror provides high modal discrimination in a Nd:YAG laser
      cavity. Single-spatial-mode lasers with high Fresnel numbers are possible, with
      negligible loss to the fundamental mode.

PMID- 19855713
TI  - Highly efficient parametric conversion of femtosecond Ti:sapphire laser pulses at
      1 kHz.
AB  - Pulses with energies as high as 150 microJ and durations as low as 60 f(s) were
      generated from 1.1 to 2.6 microm by a traveling-wave parametric converter pumped
      by femtosecond pulses of a Ti:sapphire laser with chirped-pulse amplification.

PMID- 19855715
TI  - Compression-tuned single-frequency Bragg grating fiber laser.
AB  - Compressive stress has been used to continuously wavelength tune a single
      frequency Bragg grating fiber laser over 32 nm without mode hopping. A master
      oscillator/power-amplifier configuration and active noise reduction were
      implemented to maintain a constant, low-noise, 3-mW lasing power over the tuning
      range.

PMID- 19855716
TI  - Room-temperature continuous-wave upconversion laser at 455 nm in a Tm(3+)
      fluorozirconate fiber.
AB  - A room-temperature blue upconversion laser operating at 455 nm is demonstrated in
      a Tm(3+) -doped fluorozirconate fiber when the laser is excited simultaneously at
      645 and 1064 nm, permitting as much as 3 mW of cw blue laser output.

PMID- 19855717
TI  - Third-order-harmonic mode locking of a bulk erbium:ytterbium:glass laser at a 2.5
      GHz repetition rate.
AB  - A bulk erbium:ytterbium:phosphate glass laser has been actively mode locked at
      the third-order harmonic by a bulk lithium niobate phase modulator. Light pulses
      of 9.6-ps duration, 2.5-GHz repetition rate, and 3-mW average power at 1530-nm
      wavelength have been obtained.

PMID- 19855718
TI  - Self-mode-locked diode-pumped Cr:LiSAF laser.
AB  - We describe an all-solid-state tunable self-mode-locked Cr:LiSAF laser that is
      pumped with a single 250-mW laser diode and produces almost-bandwidth-limited
      pulses of 97-fs duration. The self-mode locking is initiated by a regeneratively
      driven acousto-optic modulator, and the cavity incorporates a hard aperture in
      the form of an adjustable slit. The design considerations for low-threshold self
      mode-locked diode-pumped lasers are outlined.

PMID- 19855719
TI  - Optical switching and logic gates with vertical cavity surface-emitting lasers.
AB  - We consider a cylindrical vertical cavity surface-emitting laser with a square
      shaped active region, operating with the two Gauss-Hermite modes TEM(10) and
      TEM(01). Using a rate-equation model that includes the effects of the linewidth
      enhancement factor, we identify in the parameter space two bistability domains.
      The two stable states are in one case the doughnut modes and in the other the
      modes TEM(10) and TEM(01). Focusing on the latter case, we study numerically the
      conditions for optical switching from one mode to the other on injection of an
      appropriate control beam, and we demonstrate the possibility of using the laser
      as a NOR logic gate.

PMID- 19855720
TI  - Modeling of terahertz radiation from biased photoconductors: transient velocity
      effects.
AB  - We include transient carrier velocity dynamics in a model describing the
      terahertz radiation from a large-aperture, biased photoconductor triggered by an
      ultrashort optical pulse. Waveforms of the radiated electric field are calculated
      as a function of optical excitation fluence and bias field. The model is applied
      to terahertz generation in biased GaAs photoconductors.

PMID- 19855721
TI  - Frequency-domain interferometer for measuring the phase and amplitude of a
      femtosecond pulse probing a laser-produced plasma.
AB  - A frequency-domain interferometer for probing the variations of the dielectric
      constant of a plasma with sub-100- fs temporal resolution and lambda/2000 phase
      resolution is described. Imaging the plasma on the entrance slit of a
      spectrograph provides spatial resolution along a diameter of the focal spot. The
      technique is used to map out the expansion of the critical density surface of a
      femtosecond laser-produced plasma with subnanometer spatial resolution along the
      laser axis.

PMID- 19855722
TI  - Broadly tunable 30-fs pulses produced by optical parametric amplification.
AB  - Broadly tunable 30-fs pulses have been generated by parametric amplification of a
      white-light continuum at kilohertz repetition rates.

PMID- 19855723
TI  - Characteristics of femtosecond pulses near 1.5 microm in a self-mode-locked
      Cr(4+):YAG laser.
AB  - The operating characteristics of a self-mode-locked Cr(4+) :YAG laser that
      produces sub-100-fs pulses are described. Stable, nearly transform-limited pulses
      are obtained at a central wavelength longer than 1.50 microm, and the spectrum of
      the wavelength is extended past 1.60 microm, over the net gain bandwidth of the
      laser material. The group-velocity dispersion and the third-order dispersion of
      the Cr-doped YAG rod are measured by a Fourierindicating that the group-velocity
      dispersion vanishes at a transform interferometric cross-correlation technique,
      wavelength of 1.59 microm.

PMID- 19855724
TI  - Direct measurement of prepulse suppression by use of a plasma shutter.
AB  - A direct measurement is presented that quantifies prepulse reduction in an
      intense, ultrashort pulse on reflection from a high-density plasma created from a
      SiO(2) target at Brewster's angle. The contrast between the intense ultrashort
      pulse and prepulse energy was improved by a factor of >625. Pulse-width
      reduction, spectral broadening, and spatial filtering are also observed in the
      reflected pulse.

PMID- 19855725
TI  - Solid-state laser system for the generation of midinfrared femtosecond pulses
      tunable from 3.3 to 10 microm.
AB  - A tunable regenerative Ti:sapphire amplifier system working at a 1-kH(z)
      repetition rate pumps an optical parametric generator providing near-infrared
      pulses tunable in the wavelength range from 1 to 2.5 microm. The signal and idler
      pulses with a duration below 100 fs are mixed in a AgGaS(2) crystal to generate
      pulses at the difference frequency. The midinfrared output is continuously
      tunable between 3.3 and 10 microm, with pulse energies of as high as 50 nJ and
      durations of 160 fs, as directly determined from cross-correlation measurements.

PMID- 19855726
TI  - Self-organized learning of purely temporal information in a photorefractive
      optical resonator.
AB  - A photorefractive resonator containing an optical delay line is shown to learn
      temporal information through a self-organization process. We present experiments
      in which a resonator mode selectively learns the mostfrequently presented signals
      at the input. We also demonstrate the self-organized association of two different
      analog signals with two different resonator modes.

PMID- 19855728
TI  - Refractive-index control with strong fields.
AB  - An electromagnetically induced transparency-like effect is described that allows
      a strong laser to control and reduce to unity the refractive index of a weak
      probe. A lossless multistate system with all states far from resonance is
      considered.

PMID- 19855727
TI  - Optimization of the field of view of a Brillouin-enhanced four-wave-mixing phase
      conjugator.
AB  - A Brillouin-enhanced four-wave mixing phase conjugator featuring a field of view
      that varies by approximately an order of magnitude, i.e., from 2 to 20 mrad, is
      described. We control this variable field of view by utilizing a slightly
      noncollinear pumping geometry and by adjusting the pump-pump frequency difference
      to optimize the phase mismatch for the overall process. A model that describes
      the interplay between frequency and geometry to the Brillouin-enhanced four-wave
      mixing phase mismatch is found to predict the expandable field of view.

PMID- 19855729
TI  - Laser-induced fluorescence spectroscopy of the (0, 0) Schumann-Runge band of
      O(2).
AB  - We report laser-induced fluorescence recording and identification of the R and P
      branches (J = 1-21) of the (0, 0) Schumann-Runge band of molecular oxygen,
      excited near 202 nm by a tunable pulsed laser beam (3-MW/cm(2) maximum
      intensity). The intensity of the excitation spectrum varies linearly with the
      density of the laser power. In the conditions of the experiment, the detection
      limit of ground-state O(2) molecules deduced from the R(5) line is ~10(15) cm(
      3).

PMID- 19855730
TI  - Radiometric model for propagation of coherence.
AB  - A radiometric model for the propagation of coherence is formulated, which greatly
      simplifies the determination of the cross-spectral density and of the spectral
      degree of coherence of the field at an arbitrary distance from any planar,
      secondary, quasi-homogeneous source. The radiance function, which plays a central
      role in this model, satisfies all the postulates of traditional radiometry.

PMID- 19855731
TI  - Implementation and characterization of fiber Bragg gratings linearly chirped by a
      temperature gradient.
AB  - We propose a new method for introducing a chirp on a fiber Bragg grating.
      Uniformly written fiber Bragg gratings are linearly chirped through the use of a
      controllable temperature gradient device. This device allows the linear chirp
      conditions to be totally adjustable in a nondestructive repeatable manner. These
      conditions can be selected with great precision and are very stable, once
      defined. To characterize the resulting chirped gratings, we have measured their
      dispersion. Dispersion of the order of 200 ps/nm have been obtained for 1-cm-long
      fiber Bragg gratings with temperature gradients near 20 degrees C.

PMID- 19855732
TI  - Simple prism-based scheme for fabricating Bragg gratings in optical fibers.
AB  - A modified prism-based method for fabricating Bragg gratings in optical fibers is
      introduced. We have made an optical fiber Bragg grating at 799.67 nm by using a
      45 degrees right-angle prism and a frequency-doubled argon-ion laser at 244 nm.
      The advantage of this method is ease of alignment.

PMID- 19855733
TI  - Effects of charge spreading on resolution of optically addressed spatial light
      modulators.
AB  - A transient charge-transport model is developed to evaluate the resolution limits
      of optically addressed spatial light modulators. The effect of bulk charge
      diffusion on resolution is largely independent of the mobility in the
      semiconductor layer, and the resolution is limited by the lateral diffusion
      length of charge carriers in transit. The effects of charge drift, diffusion, and
      trapping at the interface between the semiconductor and the lightmodulating layer
      depend strongly on the interface properties. The resolution ranges from 2 to 700
      line pairs/mm for respective diffusion lengths of 16.1 to 0.16 microm at the
      interface.

PMID- 19855735
TI  - Source characterization for x-ray proximity lithography.
AB  - Calibrated x-ray spectra from laser-produced plasmas of materials with atomic
      numbers varying between 12 (Mg) and 83 (Bi) were recorded to optimize the
      conversion efficiency for proximity lithography in a 0.5-nm band centered at 1
      nm. The highest efficiency (~0.8%) was found for L-shell emitters such as Cu ando
      M-shell emitters such as Ba. First-order debris measurements were carried out by
      measurement of the layer thickness deposited on witness plates 2 cm away from the
      target. Layers of 30-nm thickness were deposited in a single laser shot with Au
      and W targets.

PMID- 19855734
TI  - In-line fiber-optic components using Langmuir-Blodgett films.
AB  - Langmuir-Blodgett (LB) films of omega-tricosenoic acid are deposited onto side
      polished optical fibers, resulting in wavelength-selective elements. The
      wavelength response is shown to be strongly dependent on film thickness, giving a
      shift in central wavelength with film thickness of Deltalambda(0)/Deltad = 2.4,
      in agreement with a simple phasematching model. It is demonstrated that an
      alternative polishing technique, requiring no substrates or epoxy, allows more
      repeatable LB deposition and produces devices with similar characteristics. This
      is the only technique that will allow deposition of more complex electro-optic LB
      film-forming molecules.

PMID- 19855737
TI  - Intensity-dependent transmission properties of window materials at 193-nm
      irradiation.
AB  - We measured the transmission of MgF(2), CaF(2), BaF(2), and fused-silica window
      materials, using 0.8-ps optical pulses at 193 nm with intensities from 1 to 300
      GW/cm(2). The two-photon absorption coefficients beta are extracted from these
      measurements. The excited excitonic fluorescence in CaF(2) and BaF(2) shows a
      quadratic dependence on the irradiation intensity in a wide range.

PMID- 19855736
TI  - Long-term storage of a soliton bit stream by use of phase-sensitive
      amplification.
AB  - We propose long-term storage of a soliton bit stream in a fiber ring in which
      loss is compensated by phase-sensitive amplification. We show that the 1's
      (soliton pulses) are asymptotically stable and that the noise on the 0's of the
      bit stream (absence of a soliton) is bounded. Moreover, the soliton-soliton
      interaction is efficiently suppressed by the phase-sensitive amplifiers.

PMID- 19855738
TI  - Digital communication with synchronized chaotic lasers.
AB  - We propose a scheme for encoding digital data within a spiky chaotic carrier from
      a loss-modulated solid-state laser. Decoding is performed in real time with a
      synchronized chaotic laser system.

PMID- 19855739
TI  - Acousto-optically induced unidirectional and single-frequency operation of a
      Nd:glass ring laser based on the acousto-optic effect in the laser medium.
AB  - A traveling-wave acousto-optic modulator fabricated from Nd-doped phosphate glass
      is used both as the laser gain medium and as the unidirectional element in a
      diode-pumped ring laser. Unidirectional operation can be maintained with applied
      rf powers as low as 6.7 mW and results in cw single-frequency output powers as
      high as 200 mW for a pump power of 1.2 W.

PMID- 19855740
TI  - Possible correlation between blood glucose concentration and the reduced
      scattering coefficient of tissues in the near infrared.
AB  - Tissue glucose levels affect the refractive index of the extracellular fluid. The
      difference in refractive index between the extracellular fluid and the cellular
      components plays a role in determining the reduced scattering coefficient
      (micro(s)') of tissue. Hence a physical correlation may exist between the reduced
      scattering coefficient and glucose concentration. We have designed and
      constructed a frequency-domain near-infrared tissue spectrometer capable of
      measuring the reduced scattering coefficient of tissue with enough precision to
      detect changes in glucose levels in the physiological and pathological range.

PMID- 19855741
TI  - Soliton self-frequency shift for pulses with a duration less than the period of
      molecular oscillations.
AB  - The effect of stimulated Raman scattering on soliton propagation in fibers is
      studied for pulse durations comparable with or shorter than the molecular
      oscillation period. The self-frequency shift of a soliton in this interaction
      regime is calculated to be inversely proportional to the soliton duration and
      does not depend on both the characteristic frequency of the molecular
      oscillations and the Raman gain width of the medium.

PMID- 19855742
TI  - Continuous-wave laser beam fanning in organic solutions: a novel phenomenon.
AB  - If a low-power cw Ar(+) laser beam (~50 mW) is sent horizontally and focused on
      the entrance side of a cuvette containing an absorptive solution, the beam fans
      into the lower half of the cuvette instead of propagating through and forming
      self-phase-modulation fringes. We call this phenomenon self-beam fanning, which
      has been observed in several organic solutions. We present here several
      experimental results and a descriptive model of the phenomenon.

PMID- 19855743
TI  - Low-intensity degenerate four-wave mixing at the cesium D1 resonance in thin
      cells.
AB  - We observed low-intensity cw degenerate four-wave mixing at the D1 resonance in a
      10-microm-thick cesium-vapor cell. Normal population depletion caused by optical
      pumping is alleviated by frequent atom-wall collisions. The reflectivity at the
      D1 resonance is approximately equal in magnitude to that observed at the D2
      cycling transition under similar conditions.

PMID- 19855744
TI  - Dual-wavelength source of high-repetition-rate, transform-limited optical pulses
      for soliton transmission.
AB  - I show how removal of the central optical frequencies from the output of an
      externally phase-modulated, single-frequency laser results in a dual-wavelength
      source of high-quality pulse trains for wavelength-division-multiplexed soliton
      transmission and describe successful experimental demonstration of such sources
      in the 2.5-12.6-Gbit/s range.

PMID- 19855745
TI  - Compensation of the soliton self-frequency shift with phase-sensitive amplifiers.
AB  - We analyze the effect of Raman scattering and higher-order dispersion on the
      propagation of short (1-ps) pulses in a nonlinear optical fiber in which the loss
      is balanced by a periodic chain of phase-sensitive, degenerate parametric
      amplifiers. The analysis shows that the Raman scattering does not induce a
      continuous frequency downshift on the pulse but only a small, finite frequency
      shift. Pulse propagation is governed by a nonlinear fourth-order evolution
      equation that admits stable solutions that propagate with a small, constant,
      inverse velocity in the group-volocity rest frame.

PMID- 19855746
TI  - Two-wave mixing of focused Gaussian beams in photorefractive waveguides.
AB  - We report two-wave mixing measurements in ion-implanted KNbO(3) planar waveguides
      and their numerical analysis in the framework of a two-dimensional model that
      takes the lateral intensity distribution of the two beams into account. We
      demonstrate that the gain and its time response can be interpreted in terms of an
      apparent interaction length and a spatially varying time constant.

PMID- 19855747
TI  - Stability of soliton propagation with sliding-frequency guiding filters.
AB  - We report on extensive experimental measurement of the allowable range of soliton
      pulse energies for stable, error-free propagation with sliding-frequency guiding
      filters, as a function of both filter strength and sliding rate, and on
      interpretative numerical analysis. The most important result is our discovery of
      an upper bound and related optimum value for the filter strength; at the optimum,
      the allowed range of pulse energies is nearly two to one.

PMID- 19855748
TI  - Dark soliton sideband formation and stability in periodically amplified systems.
AB  - We investigate the stability of dark solitons with respect to periodic
      amplification by studying sideband generation. It is shown that these sidebands
      grow exponentially as a result of a four-wave mixing process with the cw
      background. We derive expressions for the positions of the sidebands and present
      numerical simulations that are in excellent agreement with the theoretical
      description. A comparison is made with bright solitons, showing that dark soliton
      propagation is less perturbed only over very short amplifier chains. We also
      relate our results to laser cavities and discuss the prospects for dark soliton
      lasers.

PMID- 19855749
TI  - Optical autocorrelator that uses a surface-emitting second-harmonic generator on
      (211)B GaAs.
AB  - An optical autocorrelator grown on a (211)B GaAs substrate that uses visible
      surface-emitted second-harmonic generation is demonstrated. The (211)B
      orientation needs TE mode excitation only, thus eliminating the problem of the
      beating between the TE and TM modes that is required for (100)-grown devices; it
      also has the advantage of giving higher upconversion efficiency than (111)
      growth. Values of waveguide loss and the difference in the effective refractive
      index between the TE(0) and TE(1) modes were also obtained from the
      autocorrelation experiment.

PMID- 19855750
TI  - Mechanism of refractive-index change in a Ce:SBN single crystal illuminated by
      nominal homogeneous light.
AB  - We report a series of experiments demonstrating that the refractive index n(e) of
      a single crystal of Ce:SBN increases when the crystal is illuminated by a nominal
      homogeneous Ar laser beam. The increase is larger than that owing to the pure
      temperature rise, which is equal to that occurring in a Ce:SBN crystal
      illuminated by the same laser beam. We discovered that the difference between
      these Deltan(e)'s owing to the light and to the heat caused by this light is
      closely related to the crystal's history of illumination; the more it is
      illuminated, the less the difference is. Also, when the illumination exceeds the
      threshold volume for the first time, the refractive index will increase to be
      linear. We believe this to be the first report of these phenomena; we have
      introduced a theoretical explanation.

PMID- 19855751
TI  - Long-distance soliton transmission with a nonlinear twin-core fiber.
AB  - We numerically demonstrate soliton transmission over long distances in a new
      regime in which the soliton evolves in a two-core fiber over many dispersion
      lengths between successive amplifications. Shorter pulses than those transmitted
      in the average soliton dynamics regime are predicted, while a significant drift
      of the soliton mean frequency owing to the soliton self-frequency shift is
      observed and controlled by appropriate gain and loss parameters.

PMID- 19855752
TI  - Polarization-maintaining fiber Fabry-Perot tunable filters.
AB  - We report what are to our knowledge the first high-performance polarization
      maintaining single-mode fiber Fabry-Perot tunable filters. These filters
      simultaneously exhibited a loss of <2.5 dB, a finesse between 150 and 310, and an
      extinction ratio of >30 dB. A unique fabrication technique is developed that
      utilizes the tunability and the polarization resonance splitting inside the
      filter to align the birefringent axes at a pigtail-cavity joint. A general
      criterion is established for aligning polarization-maintaining fibers with
      elliptical inputs.

PMID- 19855753
TI  - Er(3+):Yb(3+)-codoped fiber distributed-feedback laser.
AB  - We report what is to our knowledge the first fiber distributed-feedback laser
      using a single Bragg grating at 1.5 microm written directly into a 2-cm-long
      Er(3+)-doped fiber codoped with Yb(3+). We obtained robust single-frequency
      operation by either using one end reflector or locally heating the center of the
      grating to create the necessary phase shift.

PMID- 19855754
TI  - Higher-order effects in bandwidth-limited soliton propagation in optical fibers.
AB  - By means of numerical studies and soliton perturbation theory we examine the
      effects of higher-order linear and nonlinear terms in bandwidth-limited amplified
      soliton propagation. We show that these effects are responsible for strong
      reductions of soliton-soliton interaction in such systems.

PMID- 19855755
TI  - Theoretical and experimental comparison of an adjustable Y-junction switch.
AB  - An optical switch using an adjustable Y-junction structure has been designed,
      fabricated, measured, and analyzed. Both the experimental performance and
      theoretical prediction of the switch are presented. The switching section of the
      device consists of three arrow-shaped, field-induced waveguides that overlap in
      the propagation direction such that input light from the middle guide can be
      transferred to either of the output guides. A cross talk of less than -18 dB is
      measured at a wavelength of 1.06 microm in a device with a transition length of
      400 microm and a branching angle of 4 degrees . Numerical simulations using the
      finite difference beam propagation method show that a cross talk of less than -22
      dB may be achievable for these device dimensions.

PMID- 19855756
TI  - Efficient method of coupling from a single-mode fiber to a thin-film waveguide.
AB  - A new method of coupling from a single-mode fiber to a thin-film waveguide
      through a coupling fiber is reported. This method provides high coupling
      efficiency, whereby the coupling fiber helps to match the coupling conditions.
      Experimentally the maximum coupling efficiency of 78% was obtained by use of a
      polymeric thin-film waveguide, in which propagation loss of the film and other
      coupling means to measure characteristics of the polymeric films.

PMID- 19855757
TI  - Propagation characteristics of planar segmented waveguides with parabolic index
      segments.
AB  - We have analyzed the linear propagation characteristics of planar periodic
      segmented waveguides with infinitely extended parabolic refractive-index segments
      in the transverse direction, using the matrix formulation of Gaussian beam
      propagation. Modal propagation and the variation of effective index as a function
      of duty cycle and the period of segmentation have been studied. Conditions for
      the existence of guided modes in such a segmented waveguide are presented.

PMID- 19855758
TI  - All-solid-state single-mode sum-frequency generation of sodium resonance
      radiation.
AB  - We have generated 65 mJ of single-mode sodium resonance radiation in 20-ns
      duration pulses by the sum-frequency mixing of the output from two injection
      seeded pulsed Nd:YAG lasers operating at 20 Hz. The observed spectral linewidth
      of the 589.158-nm radiation is measured to be less than 100 MHz, and the
      frequency stability is better than 100 MHz/h.

PMID- 19855759
TI  - All-solid-state self-mode locking of a Nd:YLF laser.
AB  - An all-solid-state, Kerr-lens mode-locked Nd:YLF laser is reported that uses a
      simple X-fold cavity with separate gain and nonlinear media. Self-starting pulses
      of 3 ps are reported at 1.047 microm with significant enhancements in stability
      and starting behavior over previous Kerr-lens mode-locked Nd:YLF lasers. The
      benefits of this X-fold cavity design for general passive mode locking of laser
      diode-pumped solid-state lasers are also addressed.

PMID- 19855760
TI  - Picosecond switching of GaAs/AlGaAs smart pixels.
AB  - We demonstrate that GaAs/AlGaAs smart pixels can be operated with picosecond and
      subpicosecond laser pulses. Switching times as short as 200 ps are measured. Our
      results confirm the theoretical prediction that input mode-locked pulses are more
      advantageous than the more typical square-wave pulses. They also suggest that use
      of picosecond mode-locked pulses for optical output could produce operating
      speeds in the gigahertz range.

PMID- 19855761
TI  - Injection locking of an actively mode-locked semiconductor laser.
AB  - We report what is to our knowledge the first observation of synchronous coherent
      injection locking of an actively mode-locked extended cavity semiconductor laser
      to an external light pulse train. In the temporal domain, we observed
      experimentally and verified theoretically a significant narrowing of the output
      pulse of the mode-locked laser. In the spectral domain, we demonstrated
      experimentally the narrowing of the output optical spectrum that was due to
      rejection of spectral components outside the spectral band of the locking pulses.
      Locking ranges, in the time and the frequency domains, were measured to be ~200
      ps and ~5 nm, respectively.

PMID- 19855762
TI  - Enhanced uniform phase conjugation in two-section asymmetric laser diodes.
AB  - Nearly degenerate four-wave mixing in two-section single-mode laser diodes with
      unequal (asymmetric) facet reflectivities is studied theoretically. It is
      demonstrated that, under appropriate biasing conditions, the device exhibits a
      uniform phase-conjugate reflectivity over a frequency detuning range of more than
      10 GHz. We can simultaneously achieve enhancement of the four-wave-mixing
      bandwidth and efficiency by injecting the probe signal at and deriving the
      conjugate output from the low-reflectivity facet of an asymmetric two-section
      laser diode.

PMID- 19855763
TI  - Thick plasma gratings using a local photorefractive effect in CdZnTe:In.
AB  - Diffraction gratings have been encoded in bulk Cd(0.8)Zn(0.2)Te:In samples by
      near-band-gap excitation. The photoinduced index change is associated with
      persistent photoconductivity resulting from ionization of DX centers. The
      gratings have a thickness of 1.7 mm, as evinced by Bragg selectivity during the
      readout process. Encoded grating are shown to be persistent for sufficiently low
      temperatures and are not erased by subsequent writing of more gratings.

PMID- 19855764
TI  - High-resolution oxygen absorption spectrum obtained with an external-cavity
      continuously tunable diode laser.
AB  - We have measured the electronic absorption spectrum of the oxygen (O(2)) A band
      b(1)Sigma(+)(g)(nu' =0)? X(3)Sigma(-)(g)(nu'' = 0) near 760 nm in room air by
      using a newly available external-cavity diode laser. The external-cavity diode
      laser permitted a continuous, single-mode scan of the P branch of ambient oxygen
      by 2f modulation spectroscopy. The external-cavity diode laser opens up many
      applications limited in the past by the noncontinuous tunability of standard
      monolithic Fabry-Perot cavity laser designs. Specifically, absorption transitions
      that coincide with he gain bandwidth of any available diode laser (635 to 1550
      mn) may now be reached without the problems and imitations imposed by mode hops
      inherent in standard Fabry-Perot cavity designs.

PMID- 19855765
TI  - Dynamical and noise properties of laser diodes subject to strong optical
      feedback.
AB  - Dynamical and noise properties of laser diodes subject to strong optical feedback
      have been investigated. Under strong optical feedback a conventional rate
      equation approach is not valid, and thus an iterative traveling-wave model has
      been developed to describe this operating regime. Attention has been given to
      identifying the transition from stable strong-feedback operation to the coherence
      collapse regime obtained with moderate optical feedback.

PMID- 19855766
TI  - Effect of initial space distribution on the temporal form of ultrashort light
      pulses in the focal plane of a lens.
AB  - It is shown that by varying the space distribution of the pulse before the
      focusing lens it is possible to control the temporal shape of the pulse in the
      focal plane. The consideration is based on representation of the light pulse as a
      superposition of Bessel or nondiffracting beams. The analytical expression for
      the spatial and temporal form of a pulse in the focal plane is found.

PMID- 19855767
TI  - Diode-pumped 100-fs passively mode-locked Cr:LiSAF laser with an antiresonant
      Fabry-Perot saturable absorber.
AB  - We demonstrate a self-starting passively mode-locked diode-pumped Cr:LiSAF laser,
      achieving pulses as short as 98 fs with an average power as high as 50 mW. In
      continuous-wave operation, we demonstrate 140 mW of output power with a
      tunability of 100 nm FWHM. These results were achieved by use of lower Cr(3+)
      doping (1.5%), high-brightness diode lasers pumping from both sides of the
      crystal, and a low-loss antiresonant Fabry-Perot saturable absorber to start and
      sustain mode-locked operation.

PMID- 19855768
TI  - Pulse shortening in a Nd:glass laser by gain reshaping and soliton formation.
AB  - We demonstrate that intracavity filtering and soliton formation in actively mode
      locked lasers can lead to pulse shortening by as much as a factor of 30. Pulses
      as short as 310 fs have been generated from a Nd:glass laser that is mode locked
      only by an acousto-optic modulator.

PMID- 19855769
TI  - Self-phase modulation in chirped-pulse amplification.
AB  - The effect of self-phase modulation in chirped-pulse amplification is
      investigated. A numerical model is used to predict the effects of phase
      modulation on pulse recompression, and experimental results are presented that
      agree well with the calculations. We show that even moderate self-phase
      modulation can significantly distort the recompressed pulse after amplification,
      thereby reducing the peak power and degrading the pulse contrast.

PMID- 19855770
TI  - Pulse retrieval in frequency-resolved optical gating based on the method of
      generalized projections.
AB  - We use the algorithmic method of generalized projections (GP's) to retrieve the
      intensity and phase of an ultrashort laser pulse from the experimental trace in
      frequency-resolved optical gating (FROG). Using simulations, we show that the use
      of GP's improves significantly the convergence properties of the algorithm over
      the basic FROG algorithm. In experimental measurements, the GP-based algorithm
      achieves significantly lower errors than previous algorithms. The use of GP's
      also permits the inclusion of an arbitrary material response function in the FROG
      problem.

PMID- 19855771
TI  - Coaxial architecture of an optical neural network with a lenslet array.
AB  - A theoretical limitation on the neuron numbers (N x N) of a spatial
      interconnection system based on a lenslet array is analyzed. To improve the
      limitation, we propose a submatrix coaxial interconnection architecture. Off
      axial aberration is decreased, and high light efficiency is achieved. A detailed
      analysis is given.

PMID- 19855772
TI  - Real-time pattern recognition system based on a bipolar winner-take-all model
      with a threshold.
AB  - A threshold is added to recognize an input pattern that has too few similarities
      to be one of the memory patterns. A real-time pattern recognition system based on
      the improved model is given. The unipolar optical pattern recognition system has
      all the characteristics of a fully bipolar winner-take-all model and has
      illumination invariance. A liquid-crystal spatial light modulator is used as a
      real-time input device, and a mask and a lens array perform the threshold and
      weighted sums of the input pattern. Some experimental results are also shown.

PMID- 19855773
TI  - Hybrid sparse-wavelength angle-multiplexed optical data storage system.
AB  - We propose, analyze, and demonstrate a hybrid wavelength-and-angle-multiplexed
      optical data storage system. Our system utilizes multiwavelength information
      processing in conjunction with angle-multiplexed volume holographic storage,
      achieving direct compatibility with wavelength-encoded optical logic processors.
      Such a scheme also allows for rapid recall of high-density data into electronic
      processing and display systems. Hybridization of wavelength and angle
      multiplexing relaxes demands on spectral and angle-tuning sources and allows for
      the use of present-day-available optical sources and components.

PMID- 19855774
TI  - Nonincremental interferometric fiber-optic measurement method for simultaneous
      detection of temperature and strain.
AB  - A nonincremental interferometric fiber-optic measurement method for simultaneous
      detection of temperature and strain is reported. The method is based on the joint
      evaluation of the fiber-optical path length and of the fiber dispersion by means
      of nonincremental interferometric phase readings at two different wavelengths.
      The joint use of a low-coherence source and of multiple optical filtering of the
      interference term permits effective setting up of the method. The experimental
      results prove a strain measurement precision of approximately 10 micro m in the
      presence of temperature variation of 30 degrees C.

PMID- 19855775
TI  - Combined temperature and strain measurement with a dispersive optical fiber
      Fourier-transform spectrometer.
AB  - We report simultaneous measurement of strain and temperature in single-mode
      optical fiber by broadband interferometry. A Mach-Zehnder interferometer,
      illuminated by a xenon-arc lamp, has a sensing element in one arm. Scanning an
      air path generates interferograms that are calibrated by a monochromatic
      reference interferogram. Values of group delay and dispersion, obtained from the
      phase of the fast Fourier transform of the sampled interferogram, give strain and
      temperature through a well-conditioned matrix transformation without phase
      ambiguity. We obtained measurement ranges and resolutions of 1500 +/- 12
      microstrain and 25.0 +/- 0.4 K using a 0.8-m sensing element.

PMID- 19855776
TI  - Influence of glucose concentration on light scattering in tissue-simulating
      phantoms.
AB  - The presence of glucose dissolved in an aqueous solution increases the refractive
      index of the solution and therefore has an influence on the scattering properties
      of any particles suspended within it. We present experimental data on the effect
      of glucose concentration on the scattering coefficient of a suspension of
      spherical polystyrene particles. The experimental results are in good agreement
      with Mie theory. The effect of glucose on light transport in highly scattering,
      tissue-simulating phantoms is demonstrated both experimentally and theoretically
      by application of diffusion theory. The possible application of this effect for
      noninvasive glucose monitoring of diabetic patients is discussed.

PMID- 19855777
TI  - Reconstructing the Hartley intensity spectrum from its sinusoidal crossings.
AB  - It is shown that a 2M-point representation I(H)(f) of the Hartley intensity
      spectrum I(Ha)(f) can be reconstructed from the intersections of I(Ha)(f) with
      the reference sinusoid R(f) of period 2delta. As required by the Nyquist sampling
      criterion, one sinusoidal crossing is detected within every frequency interval
      delta when the bandwidth of I(H)(f) is 2Mdelta. Specifically, the 2M crossings
      are used to determine the 2M expansion coefficients [h(mDelta)] of I(H)(f) with
      respect to the Hartley basis functions: cass(2pifmDelta), where Delta = /Mdelta
      and m = -M, -M + 1, ...,M. An accurate and efficient algorithm for computing
      [h(mDelta)] from the sinusoidal crossings also is proposed and demonstrated.

PMID- 19855778
TI  - Measuring the transport mean free path using a reference random medium.
AB  - The transport mean free path of microwave radiation in a random sample is
      determined from measurements of transmission through a composite sample of the
      medium with unknown scattering characteristics and a random medium of variable
      thickness and known scattering parameters. The method can be applied at optical
      frequencies by use of a ceramic wedge as the medium of variable thickness.

PMID- 19855779
TI  - Wide-angle propagating beam analysis based on the generalized Douglas scheme for
      variable coefficients.
AB  - The generalized Douglas scheme is applied to the finite-difference beam
      propagation method (FD-BPM) with a (1, 1) Pade approximant operator. A truncation
      error of O(Deltax)(4) is found in the transverse direction. To assess the
      accuracy of the scheme, we investigate the propagation error of the fundamental
      mode in a two-dimensional tilted waveguide in terms of the coupling efficiency.
      The present scheme offers further improvement in the analysis of wide-angle beam
      propagation compared with the conventional FD-BPM.

PMID- 19855780
TI  - Self-organization of scattering in photorefractive KNbO(3) into a reconfigurable
      hexagonal spot array.
AB  - The scattering cone (~2 degrees ) from an Ar laser beam (514 nm) in
      photorefractive KNbO(3):Fe has been observed to transform into a reconfigurable
      hexagonal spot array. This phenomenon can be explained through the creation of
      laser-induced transmission and reflection grating arrays.

PMID- 19855781
TI  - Two-dimensional solitons with second-order nonlinearities.
AB  - We investigate the propagation of intense Gaussian beams in materials with
      quadratic nonlinearity. Excitation of (2 + 1) solitons is numerically predicted
      at finite phase mismatch and in the presence of linear walk-off between the
      fundamental and second-harmonic waves. The numerical results are interpreted in
      terms of the conserved quantities of the wave evolution, and the appropriate
      conditions for the experimental observation of the solitons are discussed.

PMID- 19855782
TI  - Stabilization of solitonlike pulses with a slow saturable absorber.
AB  - We show that a soliton of the nonlinear Schrodinger equation perturbed by filter
      losses and/or the finite gain bandwidth of amplifiers can be kept stable by
      saturable absorbers with a relaxation time much longer than the width of the
      soliton. This provides for ultrashort pulse generation with a slow saturable
      absorber only and may have possible applications in the stabilization of soliton
      storage rings.

PMID- 19855783
TI  - Soliton switching using cascaded nonlinear-optical loop mirrors.
AB  - We demonstrate multiple-peaked switching in a nonlinear-optical loop mirror and
      present an experimental investigation of device cascading in the soliton regime
      based on a sequence of two independent nonlinear-optical loop mirrors. Cascading
      leads to an enhanced switching response with sharper switching edges, flattened
      peaks, and increased interpeak extinction ratios. We observe that pulses emerging
      from the cascade retain the sech(2) temporal profile of a soliton with minimal
      degradation in the spectral characteristics.

PMID- 19855785
TI  - Ultrafast transient Kerr lens in solution detected by the dual-beam thermal-lens
      method.
AB  - Time profiles of a transient lens on a subpicosecond time scale are observed by
      use of a dual-beam thermal-lens configuration. On this time scale and under
      nonresonant conditions the transient lens is composed mainly of the Kerr
      response. The electronic and nuclear responses are clearly separated by the
      polarization selection.

PMID- 19855784
TI  - Operating principle, saturable loss, and self-frequency shift in Kerr-shift mode
      locked lasers.
AB  - The operating principle of a recently demonstrated new Kerr-induced ultrashort
      pulse-generation technique called Kerr-shift mode locking is analyzed. It is
      shown that in Kerr-shift mode-locked lasers an intensity-dependent red shift of
      the central laser frequency is caused by the combined action of the self-phase
      modulation that is due to the nonlinear index laser host medium and the
      Lorentzian-shaped profile of the homogeneously broadened gain. The introduction
      of a long-pass wavelength f ilter (knife-edge) transforms this intensity
      dependent frequency shift into fast self-amplitude modulation (SAM), which is
      accompanied by an additional linear red shift of the central laser frequency. The
      SAM parameter and the linear frequency shift are calculated and compared with the
      experimental results.

PMID- 19855786
TI  - Compensation of polarization mode dispersion by means of the Kerr effect for
      nonreturn-to-zero signals.
AB  - We demonstrate numerically that a compensation of the polarization mode
      dispersion can be observed for nonreturn-to-zero signals as a result of a
      trapping effect, in analogy to the well-known soliton behavior. Conditions for
      such compensation are shown, and a comparison with the soliton case is reported.

PMID- 19855787
TI  - Measurement of the Raman gain spectrum of optical fibers.
AB  - The stimulated Raman gain spectrum of optical fibers has been measured down to 6
      cm(-1) by means of short pulses. Results for parallel and perpendicular
      polarizations are reported. With this technique, we observe spectral oscillations
      arising from a Brillouin mediated coupling between cw and pulsed light.

PMID- 19855788
TI  - Spectral gain hole burning and modulation instability in a Brillouin fiber
      amplifier.
AB  - We investigate theoretically the gain spectrum of a Brillouin fiber amplifier in
      the saturated region. When the amplifier is operated in the saturated region a
      hole is burned in the single-pass Brillouin gain spectrum, and peaks appear at
      frequencies determined mainly from the round-trip time of the amplifier, causing
      modulation instability in the amplified signal. This type of modulation
      instability originates intrinsically from signal amplification by the
      counterpropagating pump beam, which is depleted by the strong signal beam.

PMID- 19855789
TI  - Measured reduction of guided-acoustic-wave Brillouin scattering in a fiber
      interferometer by time-delayed pulses.
AB  - We measure the reduction of guided-acoustic-wave Brillouin scattering phase noise
      in an optical fiber interferometer by varying the time delay between an optical
      pulse pair. Excellent suppression of the phase noise is achieved when the pulses
      have parallel polarizations and are delayed by less than 100 ps, but orthogonal
      polarizations show a residual noise level that is due to the depolarized guided
      acoustic-wave Brillouin scattering modes.

PMID- 19855790
TI  - Intensity modulation in antiresonant reflecting optical waveguides.
AB  - I provide a theoretical analysis of the refractive-index dependence of
      attenuation in antiresonant reflecting optical waveguides. The results are used
      to explain the mechanism of the intensity modulation in antiresonant reflecting
      optical waveguide structures, in terms of both reflection and interference
      phenomena in the cladding system.

PMID- 19855791
TI  - Arrayed-waveguide grating multiplexer with flat spectral response.
AB  - The design principle of a single-mode arrayed-waveguide grating multiplexer with
      flat spectral response is proposed on the basis of a discrete Fourier transform.
      By a beam propagation-method simulation, a flat spectral region (within 1-dB loss
      increase) is obtained over 57.2 GHz for 100-GHz channel spacing.

PMID- 19855792
TI  - Electro-optic tuning and sidelobe control in acousto-optic tunable filters.
AB  - Both the center wavelength and the sidelobe structure of an integrated acousto
      optic tunable filter (AOTF) are determined by the effective waveguide
      birefringence along the length of the device. By altering the birefringence by
      means of the electro-optic effect, one can control these device characteristics
      in potentially useful ways. Electro-optic tuning of the center frequency of an
      AOTF is demonstrated, and it is shown that this tuning mode, while limited to
      smaller ranges than acoustic frequency tuning, is many orders of magnitude
      faster. By use of multisection electrodes, dynamic control over the shape of the
      filter function is demonstrated. Finally, a number of practical uses of this
      technique are discussed.

PMID- 19855793
TI  - Quasi-phase-matched optical parametric amplification and oscillation in
      periodically poled LiNbO(3) waveguides.
AB  - We report quasi-phase-matched optical parametric amplification and oscillation in
      a periodically poled LiNbO(3) waveguide. Single-pass parametric gains of 4.1 dB,
      corresponding to 18%/W efficiency, were achieved at a signal wavelength of 1.55
      microm with a pump wavelength of 782.2 nm. We formed a low-finesse cavity
      resonant at both signal and idler wavelengths by attaching mirrors to the
      waveguide end faces. Parametric oscillation was observed at wavelengths between
      1.4 and 1.7 microm with a peak output power of 700 mW for pump wavelengths
      between 779 and 782 nm.

PMID- 19855795
TI  - Noncritically phase-matched Ti:sapphire-pumped femtosecond optical parametric
      oscillator based on RbTiOAsO(4).
AB  - The operation of a Ti:sapphire-laser-pumped femtosecond optical parametric
      oscillator based on the new nonlinear material RbTiOAsO(4) is described.
      Oscillation has been observed for pump powers as low as 50 mW, and output powers
      as high as 185 mW have been measured. With intracavity prisms for dispersion
      compensation, transformlimited pulses of less than 70-fs duration have been
      produced. Under noncritical phase matching, a signal (idler) tuning range over
      110 nm (330 nm) is demonstrated with pump tuning.

PMID- 19855794
TI  - Quasi-phase-matched 1.064-microm-pumped optical parametric oscillator in bulk
      periodically poled LiNbO(3).
AB  - We report a quasi-phase-matched optical parametric oscillator, using bulk
      periodically poled LiNbO(3). The optical parametric oscillator, pumped by a 1.064
      microm Q-switched Nd:YAG laser, was temperature tuned over the wavelength range
      1.66-2.95 microm. The oscillation threshold of approximately 0.1 mJ was more than
      a factor of 10 below the damage limit. The LiNbO(3) crystal, fabricated by
      application of an electric field to a sample with liquid and metal surface
      electrodes, was 0.5 mm thick with a 5.2-mm interaction length and a quasi-phase
      matched period of 31 microm.

PMID- 19855796
TI  - Effect of spatial hole burning in a mode-locked diode end-pumped Nd:YAG laser.
AB  - We have controlled the amount of spatial hole burning in a diode end-pumped
      Nd:YAG laser to quantitatively analyze its role in active mode locking. We
      demonstrate inhomogeneous broadening of the lasing bandwidth to >60 GHz,
      accompanied by a pulse-width reduction from 40 to 15 ps and an ~30% increase in
      the time-bandwidth product. Both homogeneous and inhomogeneous broadening have
      been included in a successful calculation of the steady-state pulse width.

PMID- 19855797
TI  - Significant improvement in the efficiency and brightness of the J = 0-1 19.6-nm
      line of the germanium laser by use of double-pulse pumping.
AB  - We describe significant improvement in the efficiency and brightness of the J = 0
      1 19.6-nm line of the neonlike germanium laser. A curved slab target was
      irradiated by two laser pulses of 100-ps duration separated by 300 ps with a
      total energy of 200-300 J on target. Compared with that obtained by 1-ns single
      pulse pumping with 1.1 kJ of energy, the J = 0-1 line has a 12 times higher peak
      intensity, with a smaller beam divergence of 2 mrad, corresponding to a factor-of
      25 improvement in brightness.

PMID- 19855798
TI  - Amplification of 26-fs, 2-TW pulses near the gain-narrowing limit in Ti:sapphire.
AB  - We report the generation of 26-fs-duration pulses, with an energy of 60 mJ, from
      a simple multipass Ti:sapphire amplifier system. The peak power of our amplified
      pulses is 2 TW, and the repetition rate is 10 Hz. Our amplifier design consists
      of two highly doped multipass amplifiers and is simple and compact. We use an all
      reflective, low-groove-density grating stretcher and compressor, combined with a
      relatively short material path length in the amplifier. This design allows us to
      minimize higher-order dispersion. The result is a laser system that generates
      multiterrawatt transform-limited pulses, with good beam quality and low amplified
      spontaneous-emission levels, at a duration near the theoretical limit imposed by
      gain narrowing in Ti:sapphire.

PMID- 19855799
TI  - Passively mode-locked fiber laser based on polarization rotation in a multiple
      quantum-well waveguide.
AB  - We give experimental evidence for a new type of mode-locking mechanism for Er
      doped fiber lasers based on polarization evolution in an intracavity multiple
      quantum-well waveguide. Experiments indicate that anisotropic properties of
      waveguides can continuously start the mode-locking process.

PMID- 19855800
TI  - Single-shot measurement of the amplitude and phase of ultrashort laser pulses in
      the violet.
AB  - Using single-shot, self-diffraction, frequency-resolved optical gating, we
      measure the complete electric field amplitude and phase of 405-nm second-harmonic
      pulses from an amplified Ti:sapphire system. The single-shot frequency-resolved
      optical gating device gives both qualitative and quantitative information, which
      is useful for analyzing and optimizing the grating compressor in the chirped
      pulse amplification system.

PMID- 19855801
TI  - Self-channeling of high-peak-power femtosecond laser pulses in air.
AB  - The self-channeling of ultrashort laser pulses through 20 m of air was
      demonstrated. The channeled pulse was measured to have 0.75 mJ of energy, a
      diameter of 80 microm FWHM, and a modulated spectrum. All these values were
      measured to be fairly constant during the propagation of the pulse. A preliminary
      model is shown to explain these results.

PMID- 19855802
TI  - Implementation of an optical multiwavelength full adder with a polarization
      encoding scheme.
AB  - We propose and demonstrate an optical multiwavelength full adder that uses
      polarization encoding and fourwave mixing in photorefractive crystals. Optical
      wavelengths are employed to encode the different bits of binary numbers. By
      exploiting the spectral parallelism of optics, we can perform multibit operations
      simultaneously in photorefractive crystals. The polarization encoding scheme
      permits an easy, accurate implementation of multiwavelength SUM operations. A
      carry-save full adder also is demonstrated to improve system speed further during
      multinumber addition and subtraction.

PMID- 19855803
TI  - Multiobject recognition in a multichannel joint-transform correlator.
AB  - A multichannel joint-transform correlator that incorporates a Dammann grating as
      a beam splitter is described. The Dammann grating splits a single incident beam
      into a two-dimensional array of equal-intensity beams, which form several
      channels for correlation. Each channel contains both a single target and a single
      reference. Optical experimental results are presented.

PMID- 19855804
TI  - Diffusion theory of guided photon-density waves.
AB  - Atheoretical formulation of diffuse photon-density waves propagating in a
      waveguide structure, which consists of two regions with different wave speeds, is
      presented. In comparison with the usual optical waveguides for coherent
      radiation, unique features of the guided photon-density waves are found.

PMID- 19855805
TI  - Laser spectroscopy of molecular cesium near 1064 nm enhanced by a Fabry-Perot
      cavity.
AB  - We made Doppler-broadened and Doppler-free absorption measurement of a cesium
      cell that was placed inside an external Fabry-Perot ring cavity, using a Nd:YAG
      laser. We achieved a cavity finesse of ~85, and the sensitivity of the
      measurement was improved by as much as 26.5 with respect to single-pass
      absorption. The sensitivity enhancement by the external cavity may enable one to
      lock the laser frequency to (133)Cs(2) lines at relatively low temperatures, in
      which the frequency-dependent temperature shift, as well as the collision
      broadening, is reduced significantly.

PMID- 19855806
TI  - Experimental demonstration of swept-carrier time-domain optical memory.
AB  - Swept-carrier time-domain optical memory [Opt. Lett. 17, 535 (1992)] has been
      proposed as a means of storing optical data streams in inhomogeneously broadened
      spectral recording materials. The process provides for full utilization of the
      material storage bandwidth regardless of the data rate and permits storage of
      data sequences with durations exceeding the material dephasing time. We report
      what we believe is the first experimental demonstration of this storage process.
      Our experiments, implemented with frequency-swept diode lasers and Tm(3+):YAG
      storage material, demonstrate single-event storage of 98-bit data streams whose
      duration is an order of magnitude longer than the material dephasing time.

PMID- 19855807
TI  - Two-mode fiber-optic time-delay scanner for white-light interferometry.
AB  - We present a scheme for scanning time delay by a variable-delay interferometer
      constructed from a two-mode optical fiber. The delay is generated by coupling
      between the two spatial modes of the fiber by means of acousto-optic interaction.
      The construction and performance of the system are discussed.

PMID- 19855808
TI  - Attometer resolution of wavelength shifts by use of fiber modal interferometers.
AB  - A method for on-line, real-time detection of wavelength drifts in laser diodes is
      proposed. This technique uses the wavelength dependence of the differential
      propagation constant between the LP(01)/LP(even)(11) or LP(01)/LP(02) modes in
      two-mode fibers to measure wavelength changes that manifest themselves as
      intensity modulation in the output far field. Theoretical calculations show that
      wavelength drifts of the order of 10(-18) m can be resolved by this technique.

PMID- 19855809
TI  - Diode-laser-based sum-frequency generation of tunable wavelength-modulated UV
      light for OH radical detection.
AB  - Greater than 1.5 microW of tunable wavelength-modulated 308-nm radiation was
      generated by sum-frequency mixing of 90 mW of 835-nm diode-laser output and 1.5 W
      of 488-nm Ar(+)-laser output in a beta-barium metaborate crystal. Hydroxyl
      radicals formed in a discharge-flow reactor were detected by use of the generated
      UV beam by direct absorption, wavelength-modulation absorption spectroscopy, and
      laser-induced fluorescence. Wavelength modulation with second-harmonic detection
      yielded an estimated minimum detectable absorbance of 8.5 x 10(-6) at a 1-Hz
      bandwidth. This absorbance level corresponds to an OH detection sensitivity of
      11.7 parts per trillion for a 1-m path length at 1 atm and 298 K.

PMID- 19855810
TI  - Distributed sensor for water and pH measurements using fiber optics and swellable
      polymeric systems.
AB  - We report on the design, construction and test of a generic form of sensor for
      making distributed measurements of a range of chemical parameters. The technique
      combines optical time-domain reflectometry with chemically sensitive water
      swellable polymers (hydrogels). Initial experiments have concentrated on
      demonstrating a distributed water detector; however, gels have been developed
      that enable this sensor to be readily adapted to distributed pH measurements.

PMID- 19855811
TI  - Experimental demonstration of an excited-state Faraday filter operating at 532
      nm.
AB  - We outline what is to our knowledge the first experimental demonstration of an
      excited-state Faraday filter. The filter consists of potassium vapor between
      crossed polarizers in a dc magnetic field and operates on the 4P((1/2)) ?
      8S((1/2)) transition in potassium. The 4P((1/2)) state is populated by a linearly
      polarized, 10-ns light pulse from a dye laser operating at 769.9 nm. Another
      linearly polarized, 10-nsec pulse at 532.33 nm traverses the pumped volume of the
      K cell and is absorbed from the 4P((1/2)) state to the 8S((1/2)) state. The
      transmission of the filter is approximately 3.5% at 532.33 nm with a bandwidth of
      less than 10 GHz.

PMID- 19855812
TI  - Optimal design of dual-wavelength multiple beam splitters.
AB  - Dual-wavelength multiple beam splitters (DWMBS's) are designed to split a dual
      wavelength beam into two beam arrays, one for each of the two wavelengths. These
      two beam arrays may have either the same dimension and structure or different
      dimensions and structures, depending on applications. We present results of our
      computer simulations for a 1 x 5 DWMBS that exhibits one-dimensional diffraction
      efficiency and uniformity of 83.8% and 98.4%, respectively, for a wavelength of
      514.5 nm and of 85.1% and 99.0%, respectively, for a wavelength of 632.8 nm.

PMID- 19855813
TI  - Low-cost high-speed multichannel fiber-optic correlator.
AB  - It is shown that, for stationary signals, by use of a microwave switchable delay
      line the number of channels in a multichannel fiber-optic correlator may be
      simply expanded. By replacing one optical tree with an electrical tree and by
      performing the AND operation with double-gate metal-oxide semiconductor field
      effect transistors, we demonstrate two methods of reducing the cost of a
      multichannel architecture without a reduction in speed. Using optical
      implementation for delays longer than 5 ns and microwave implementation for
      delays shorter than 5 ns, we obtain 20 points of the correlation function of a
      500-MHz signal.

PMID- 19855815
TI  - Molecular Depth Profiling using a C(60) Cluster Beam: the Role of Impact Energy.
AB  - Molecular depth profiling of organic overlayers was performed using a mass
      selected C(60) ion beam in conjunction with time-of-flight (TOF-SIMS) mass
      spectrometry. The characteristics of sputter depth profiles acquired for a 300-nm
      Trehalose film on silicon were studied as a function of the kinetic impact energy
      of the projectile ions. The results are interpreted in terms of a simple model
      describing the balance between sputter erosion and ion induced chemical damage.
      It is shown that the efficiency of the projectile to clean up the fragmentation
      debris produced by its own impact represents a key parameter governing the
      success of molecular depth profile analysis.

PMID- 19855814
TI  - A computational framework for ultrastructural mapping of neural circuitry.
AB  - Circuitry mapping of metazoan neural systems is difficult because canonical
      neural regions (regions containing one or more copies of all components) are
      large, regional borders are uncertain, neuronal diversity is high, and potential
      network topologies so numerous that only anatomical ground truth can resolve
      them. Complete mapping of a specific network requires synaptic resolution,
      canonical region coverage, and robust neuronal classification. Though
      transmission electron microscopy (TEM) remains the optimal tool for network
      mapping, the process of building large serial section TEM (ssTEM) image volumes
      is rendered difficult by the need to precisely mosaic distorted image tiles and
      register distorted mosaics. Moreover, most molecular neuronal class markers are
      poorly compatible with optimal TEM imaging. Our objective was to build a complete
      framework for ultrastructural circuitry mapping. This framework combines strong
      TEM-compliant small molecule profiling with automated image tile mosaicking,
      automated slice-to-slice image registration, and gigabyte-scale image browsing
      for volume annotation. Specifically we show how ultrathin molecular profiling
      datasets and their resultant classification maps can be embedded into ssTEM
      datasets and how scripted acquisition tools (SerialEM), mosaicking and
      registration (ir-tools), and large slice viewers (MosaicBuilder, Viking) can be
      used to manage terabyte-scale volumes. These methods enable large-scale
      connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete
      network mapping in retina), terabyte-scale image volumes that previously would
      require decades of assembly can now be completed in months. Perhaps more
      importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir
      tools volume assembly, and data viewers/annotators also allow ssTEM to be used as
      a prospective tool for discovery in nonneural systems and a practical screening
      methodology for neurogenetics. Finally, this framework provides a mechanism for
      parallelization of ssTEM imaging, volume assembly, and data analysis across an
      international user base, enhancing the productivity of a large cohort of electron
      microscopists.

PMID- 19855816
TI  - Helicobacter pylori's unconventional role in health and disease.
AB  - The discovery of a bacterium, Helicobacter pylori, that is resident in the human
      stomach and causes chronic disease (peptic ulcer and gastric cancer) was radical
      on many levels. Whereas the mouth and the colon were both known to host a large
      number of microorganisms, collectively referred to as the microbiome, the stomach
      was thought to be a virtual Sahara desert for microbes because of its high
      acidity. We now know that H. pylori is one of many species of bacteria that live
      in the stomach, although H. pylori seems to dominate this community. H. pylori
      does not behave as a classical bacterial pathogen: disease is not solely mediated
      by production of toxins, although certain H. pylori genes, including those that
      encode exotoxins, increase the risk of disease development. Instead, disease
      seems to result from a complex interaction between the bacterium, the host, and
      the environment. Furthermore, H. pylori was the first bacterium observed to
      behave as a carcinogen. The innate and adaptive immune defenses of the host,
      combined with factors in the environment of the stomach, apparently drive a
      continuously high rate of genomic variation in H. pylori. Studies of this genetic
      diversity in strains isolated from various locations across the globe show that
      H. pylori has coevolved with humans throughout our history. This long association
      has given rise not only to disease, but also to possible protective effects,
      particularly with respect to diseases of the esophagus. Given this complex
      relationship with human health, eradication of H. pylori in nonsymptomatic
      individuals may not be the best course of action. The story of H. pylori teaches
      us to look more deeply at our resident microbiome and the complexity of its
      interactions, both in this complex population and within our own tissues, to gain
      a better understanding of health and disease.

PMID- 19855817
TI  - The application of genomics to emerging zoonotic viral diseases.
AB  - Interspecies transmission of pathogens may result in the emergence of new
      infectious diseases in humans as well as in domestic and wild animals. Genomics
      tools such as high-throughput sequencing, mRNA expression profiling, and
      microarray-based analysis of single nucleotide polymorphisms are providing
      unprecedented ways to analyze the diversity of the genomes of emerging pathogens
      as well as the molecular basis of the host response to them. By comparing and
      contrasting the outcomes of an emerging infection with those of closely related
      pathogens in different but related host species, we can further delineate the
      various host pathways determining the outcome of zoonotic transmission and
      adaptation to the newly invaded species. The ultimate challenge is to link
      pathogen and host genomics data with biological outcomes of zoonotic transmission
      and to translate the integrated data into novel intervention strategies that
      eventually will allow the effective control of newly emerging infectious
      diseases.

PMID- 19855818
TI  - The role of genomics in tracking the evolution of influenza A virus.
AB  - Influenza A virus causes annual epidemics and occasional pandemics of short-term
      respiratory infections associated with considerable morbidity and mortality. The
      pandemics occur when new human-transmissible viruses that have the major surface
      protein of influenza A viruses from other host species are introduced into the
      human population. Between such rare events, the evolution of influenza is shaped
      by antigenic drift: the accumulation of mutations that result in changes in
      exposed regions of the viral surface proteins. Antigenic drift makes the virus
      less susceptible to immediate neutralization by the immune system in individuals
      who have had a previous influenza infection or vaccination. A biannual
      reevaluation of the vaccine composition is essential to maintain its
      effectiveness due to this immune escape. The study of influenza genomes is key to
      this endeavor, increasing our understanding of antigenic drift and enhancing the
      accuracy of vaccine strain selection. Recent large-scale genome sequencing and
      antigenic typing has considerably improved our understanding of influenza
      evolution: epidemics around the globe are seeded from a reservoir in East
      Southeast Asia with year-round prevalence of influenza viruses; antigenically
      similar strains predominate in epidemics worldwide for several years before being
      replaced by a new antigenic cluster of strains. Future in-depth studies of the
      influenza reservoir, along with large-scale data mining of genomic resources and
      the integration of epidemiological, genomic, and antigenic data, should enhance
      our understanding of antigenic drift and improve the detection and control of
      antigenically novel emerging strains.

PMID- 19855819
TI  - Functional interactions between the erupted/tsg101 growth suppressor gene and the
      DaPKC and rbf1 genes in Drosophila imaginal disc tumors.
AB  - BACKGROUND: The Drosophila gene erupted (ept) encodes the fly homolog of human
      Tumor Susceptibility Gene-101 (TSG101), which functions as part of the conserved
      ESCRT-1 complex to facilitate the movement of cargoes through the endolysosomal
      pathway. Loss of ept or other genes that encode components of the endocytic
      machinery (e.g. synatxin7/avalanche, rab5, and vps25) produces disorganized
      overgrowth of imaginal disc tissue. Excess cell division is postulated to be a
      primary cause of these 'neoplastic' phenotypes, but the autonomous effect of
      these mutations on cell cycle control has not been examined. PRINCIPAL FINDINGS:
      Here we show that disc cells lacking ept function display an altered cell cycle
      profile indicative of deregulated progression through the G1-to-S phase
      transition and express reduced levels of the tumor suppressor ortholog and G1/S
      inhibitor Rbf1. Genetic reductions of the Drosophila aPKC kinase (DaPKC), which
      has been shown to promote tumor growth in other fly tumor models, prevent both
      the ept neoplastic phenotype and the reduction in Rbf1 levels that otherwise
      occurs in clones of ept mutant cells; this effect is coincident with changes in
      localization of Notch and Crumbs, two proteins whose sorting is altered in ept
      mutant cells. The effect on Rbf1 can also be blocked by removal of the gamma
      secretase component presenilin, suggesting that cleavage of a gamma-secretase
      target influences Rbf1 levels in ept mutant cells. Expression of exogenous rbf1
      completely ablates ept mutant eye tissues but only mildly affects the development
      of discs composed of cells with wild type ept. CONCLUSIONS: Together, these data
      show that loss of ept alters nuclear cell cycle control in developing imaginal
      discs and identify the DaPKC, presenilin, and rbf1 genes as modifiers of
      molecular and cellular phenotypes that result from loss of ept.

PMID- 19855820
TI  - Molecular genomic approaches to infectious diseases in resource-limited settings.

PMID- 19855821
TI  - The past and future of tuberculosis research.
AB  - Renewed efforts in tuberculosis (TB) research have led to important new insights
      into the biology and epidemiology of this devastating disease. Yet, in the face
      of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance--all of
      which contribute to susceptibility to TB--global control of the disease will
      remain a formidable challenge for years to come. New high-throughput genomics
      technologies are already contributing to studies of TB's epidemiology,
      comparative genomics, evolution, and host-pathogen interaction. We argue here,
      however, that new multidisciplinary approaches--especially the integration of
      epidemiology with systems biology in what we call "systems epidemiology"--will be
      required to eliminate TB.

PMID- 19855822
TI  - The key role of genomics in modern vaccine and drug design for emerging
      infectious diseases.
AB  - It can be argued that the arrival of the "genomics era" has significantly shifted
      the paradigm of vaccine and therapeutics development from microbiological to
      sequence-based approaches. Genome sequences provide a previously unattainable
      route to investigate the mechanisms that underpin pathogenesis. Genomics,
      transcriptomics, metabolomics, structural genomics, proteomics, and immunomics
      are being exploited to perfect the identification of targets, to design new
      vaccines and drugs, and to predict their effects in patients. Furthermore, human
      genomics and related studies are providing insights into aspects of host biology
      that are important in infectious disease. This ever-growing body of genomic data
      and new genome-based approaches will play a critical role in the future to enable
      timely development of vaccines and therapeutics to control emerging infectious
      diseases.

PMID- 19855823
TI  - Toward the use of genomics to study microevolutionary change in bacteria.
AB  - Bacteria evolve rapidly in response to the environment they encounter. Some
      environmental changes are experienced numerous times by bacteria from the same
      population, providing an opportunity to dissect the genetic basis of adaptive
      evolution. Here I discuss two examples in which the patterns of rapid change
      provide insight into medically important bacterial phenotypes, namely immune
      escape by Neisseria meningitidis and host specificity of Campylobacter jejuni.
      Genomic analysis of populations of bacteria from these species holds great
      promise but requires appropriate concepts and statistical tools.

PMID- 19855824
TI  - Discovering the phylodynamics of RNA viruses.

PMID- 19855825
TI  - Computational resources in infectious disease: limitations and challenges.

PMID- 19855826
TI  - The role of medical structural genomics in discovering new drugs for infectious
      diseases.

PMID- 19855827
TI  - The role of genomics in the identification, prediction, and prevention of
      biological threats.
AB  - In all likelihood, it is only a matter of time before our public health system
      will face a major biological threat, whether intentionally dispersed or
      originating from a known or newly emerging infectious disease. It is necessary
      not only to increase our reactive "biodefense," but also to be proactive and
      increase our preparedness. To achieve this goal, it is essential that the
      scientific and public health communities fully embrace the genomic revolution,
      and that novel bioinformatic and computing tools necessary to make great strides
      in our understanding of these novel and emerging threats be developed. Genomics
      has graduated from a specialized field of science to a research tool that soon
      will be routine in research laboratories and clinical settings. Because the
      technology is becoming more affordable, genomics can and should be used
      proactively to build our preparedness and responsiveness to biological threats.
      All pieces, including major continued funding, advances in next-generation
      sequencing technologies, bioinformatics infrastructures, and open access to data
      and metadata, are being set in place for genomics to play a central role in our
      public health system.

PMID- 19855828
TI  - Can an infectious disease genomics project predict and prevent the next pandemic?
AB  - The world of genomics is transforming medicine, and is likely to influence the
      future development of new drugs, diagnostics, and vaccines. To date, the greater
      focus of genomics and medicine has been on conditions affecting resourcewealthy
      settings, primarily involving scientists and companies in those settings.
      However, we believe that it is possible to expand genomics into a more global
      technology that can also focus on diseases of resource-limited settings. This
      goal can be achieved if genomics is made a global priority. We feel one way to
      move in this direction is through a comprehensive approach to infectious diseases
      i.e., an Infectious Disease Genomics Project-that would mirror the Human Genome
      Project. Without an active, unified effort specifically focused on allowing
      actors at any level to participate in the genomics revolution, infectious
      diseases that primarily affect the poor will likely not achieve the same level of
      scientifici advancement as diseases affecting the wealthy.

PMID- 19855830
TI  - Genomics of emerging infectious disease: A PLoS collection.

PMID- 19855829
TI  - Helminth genomics: The implications for human health.
AB  - More than two billion people (one-third of humanity) are infected with parasitic
      roundworms or flatworms, collectively known as helminth parasites. These
      infections cause diseases that are responsible for enormous levels of morbidity
      and mortality, delays in the physical development of children, loss of
      productivity among the workforce, and maintenance of poverty. Genomes of the
      major helminth species that affect humans, and many others of agricultural and
      veterinary significance, are now the subject of intensive genome sequencing and
      annotation. Draft genome sequences of the filarial worm Brugia malayi and two of
      the human schistosomes, Schistosoma japonicum and S. mansoni, are now available,
      among others. These genome data will provide the basis for a comprehensive
      understanding of the molecular mechanisms involved in helminth nutrition and
      metabolism, host-dependent development and maturation, immune evasion, and
      evolution. They are likely also to predict new potential vaccine candidates and
      drug targets. In this review, we present an overview of these efforts and
      emphasize the potential impact and importance of these new findings.

PMID- 19855831
TI  - Potencies of cocaine methiodide on major cocaine targets in mice.
AB  - Cocaine methiodide (CM), a charged cocaine analog, cannot pass the blood brain
      barrier. It has been assumed the effects of systemic CM represent cocaine actions
      in peripheral tissues. However, the IC(50) values of CM have not been clearly
      determined for the major cocaine targets: dopamine, norepinephrine, and serotonin
      transporters, and sodium channels. Using cells transfected with individual
      transporters from mice and synaptosomes from mouse striatum tissues, we observed
      that the inhibition IC(50) values for monoamine uptake by CM were 31-fold to 184
      fold higher compared to cocaine at each of the transporters. In dorsal root
      ganglion neurons, cocaine inhibited sodium channels with an apparent IC(50) of 75
      microM, while CM showed no observable effect at concentrations up to 3 mM. These
      results indicate that an equal dose of CM will not produce an equivalent
      peripheral effect of cocaine.

PMID- 19855832
TI  - Dual regulation of dendritic morphogenesis in Drosophila by the COP9 signalosome.
AB  - Altered dendritic arborization contributes to numerous physiological processes
      including synaptic plasticity, behavior, learning and memory, and is one of the
      most consistent neuropathologic conditions found in a number of mental
      retardation disorders, schizophrenia, and neurodegenerative disease. COP9
      signalosome (CSN), an evolutionarily conserved regulator of the Cullin-based
      ubiquitin ligases that act in the proteasome pathway, has been found associated
      with diverse debilitating syndromes, suggesting that CSN may be involved in
      regulation of dendritic arborization. However, the mechanism of this control, if
      it exists, is unknown. To address whether the CSN pathway plays a role in
      dendrites, we used a simple and genetically tractable model, Drosophila larval
      peripheral nervous system. Our model study identified the COP9 signalosome as the
      key and multilayer regulator of dendritic arborization. CSN is responsible for
      shaping the entire dendritic tree through both stimulating and then repressing
      dendritic branching. We identified that CSN exerts its dualistic function via
      control of different Cullins. In particular, CSN stimulates dendritic branching
      through Cullin1, and inhibits it via control of Cullin3 function. We also
      identified that Cullin1 acts in neurons with the substrate-specific F-box protein
      Slimb to target the Cubitus interruptus protein for degradation.

PMID- 19855833
TI  - Tyrosine, cysteine, and S-adenosyl methionine stimulate in vitro [FeFe]
      hydrogenase activation.
AB  - BACKGROUND: [FeFe] hydrogenases are metalloenzymes involved in the anaerobic
      metabolism of H(2). These proteins are distinguished by an active site cofactor
      known as the H-cluster. This unique [6Fe-6S] complex contains multiple non
      protein moieties and requires several maturation enzymes for its assembly. The
      pathways and biochemical precursors for H-cluster biosynthesis have yet to be
      elucidated. PRINCIPAL FINDINGS: We report an in vitro maturation system in which,
      for the first time, chemical additives enhance [FeFe] hydrogenase activation,
      thus signifying in situ H-cluster biosynthesis. The maturation system is
      comprised of purified hydrogenase apoprotein; a dialyzed Escherichia coli cell
      lysate containing heterologous HydE, HydF, and HydG maturases; and exogenous
      small molecules. Following anaerobic incubation of the Chlamydomonas reinhardtii
      HydA1 apohydrogenase with S-adenosyl methionine (SAM), cysteine, tyrosine, iron,
      sulfide, and the non-purified maturases, hydrogenase activity increased 5-fold
      relative to incubations without the exogenous substrates. No conditions were
      identified in which addition of guanosine triphosphate (GTP) improved hydrogenase
      maturation. SIGNIFICANCE: The in vitro system allows for direct investigation of
      [FeFe] hydrogenase activation. This work also provides a foundation for studying
      the biosynthetic mechanisms of H-cluster biosynthesis using solely purified
      enzymes and chemical additives.

PMID- 19855834
TI  - Blocking variant surface glycoprotein synthesis in Trypanosoma brucei triggers a
      general arrest in translation initiation.
AB  - BACKGROUND: The African trypanosome Trypanosoma brucei is covered with a dense
      layer of Variant Surface Glycoprotein (VSG), which protects it from lysis by host
      complement via the alternative pathway in the mammalian bloodstream. Blocking VSG
      synthesis by the induction of VSG RNAi triggers an unusually precise
      precytokinesis cell-cycle arrest. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      characterise the cells arrested after the induction of VSG RNAi. We were able to
      rescue the VSG221 RNAi induced cell-cycle arrest through expression of a second
      different VSG (VSG117 which is not recognised by the VSG221 RNAi) from the VSG221
      expression site. Metabolic labeling of the arrested cells showed that blocking
      VSG synthesis triggered a global translation arrest, with total protein synthesis
      reduced to less than 1-4% normal levels within 24 hours of induction of VSG RNAi.
      Analysis by electron microscopy showed that the translation arrest was coupled
      with rapid disassociation of ribosomes from the endoplasmic reticulum. Polysome
      analysis showed a drastic decrease in polysomes in the arrested cells. No major
      changes were found in levels of transcription, total RNA transcript levels or
      global amino acid concentrations in the arrested cells. CONCLUSIONS: The cell
      cycle arrest phenotype triggered by the induction of VSG221 RNAi is not caused by
      siRNA toxicity, as this arrest can be alleviated if a second different VSG is
      inserted downstream of the active VSG221 expression site promoter. Analysis of
      polysomes in the stalled cells showed that the translation arrest is mediated at
      the level of translation initiation rather than elongation. The cell-cycle arrest
      induced in the presence of a VSG synthesis block is reversible, suggesting that
      VSG synthesis and/or trafficking to the cell surface could be monitored during
      the cell-cycle as part of a specific cell-cycle checkpoint.

PMID- 19855835
TI  - Poor prognosis with in vitro fertilization in Indian women compared to Caucasian
      women despite similar embryo quality.
AB  - BACKGROUND: Disease prevalence and response to medical therapy may differ among
      patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF)
      treatment have been previously shown in Indian women compared to Caucasian women,
      and some evidence suggests that poor embryo quality may be a cause for the
      discrepancy. In our center, only patients with the highest quality cleavage stage
      embryos are considered eligible for extending embryo culture to the blastocyst
      stage. We compared live birth rates (LBR) between Indian and Caucasian women
      after blastocyst transfer to investigate whether differences in IVF outcomes
      between these ethnicities would persist in patients who transferred similar
      quality embryos. METHODOLOGY/PRINCIPAL FINDINGS: In this retrospective cohort
      analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a
      blastocyst transfer between January 1, 2005 and June 31, 2007 in our university
      center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P =
      0.03), were more likely to have an agonist down regulation protocol (68% vs. 43%,
      P<0.01), and were more likely to have polycystic ovarian syndrome (PCOS),
      although not significant, (24% vs. 14%, P = 0.06). Sixty eight percent of Indian
      patients had the highest quality embryos (4AB blastocyst or better) transferred
      compared to 71% of the Caucasians (P = 0.2). LBR was significantly lower in the
      Indians compared to the Caucasians (24% vs. 41%, P<0.01) with an odds ratio of
      0.63, (95%CI 0.46-0.86). Controlling for age, stimulation protocol and PCOS
      showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40
      0.79) in the multivariate analysis. CONCLUSIONS/SIGNIFICANCE: Despite younger age
      and similar embryo quality, Indians had a significantly lower LBR than
      Caucasians. In this preliminary study, poor prognosis after IVF for Indian
      ethnicity persisted despite limiting analysis to patients with high quality
      embryos transferred. Further investigation into explanations for ethnic
      differences in reproduction is needed.

PMID- 19855836
TI  - A population rate code of auditory space in the human cortex.
AB  - BACKGROUND: Previous work on the human auditory cortex has revealed areas
      specialized in spatial processing but how the neurons in these areas represent
      the location of a sound source remains unknown. METHODOLOGY/PRINCIPAL FINDINGS:
      Here, we performed a magnetoencephalography (MEG) experiment with the aim of
      revealing the neural code of auditory space implemented by the human cortex. In a
      stimulus-specific adaptation paradigm, realistic spatial sound stimuli were
      presented in pairs of adaptor and probe locations. We found that the attenuation
      of the N1m response depended strongly on the spatial arrangement of the two sound
      sources. These location-specific effects showed that sounds originating from
      locations within the same hemifield activated the same neuronal population
      regardless of the spatial separation between the sound sources. In contrast,
      sounds originating from opposite hemifields activated separate groups of neurons.
      CONCLUSIONS/SIGNIFICANCE: These results are highly consistent with a rate code of
      spatial location formed by two opponent populations, one tuned to locations in
      the left and the other to those in the right. This indicates that the neuronal
      code of sound source location implemented by the human auditory cortex is similar
      to that previously found in other primates.

PMID- 19855837
TI  - A comparative study of Drosophila and human A-type lamins.
AB  - Nuclear intermediate filament proteins, called lamins, form a meshwork that lines
      the inner surface of the nuclear envelope. Lamins contain three domains: an N
      terminal head, a central rod and a C-terminal tail domain possessing an Ig-fold
      structural motif. Lamins are classified as either A- or B-type based on structure
      and expression pattern. The Drosophila genome possesses two genes encoding
      lamins, Lamin C and lamin Dm(0), which have been designated A- and B-type,
      respectively, based on their expression profile and structural features. In
      humans, mutations in the gene encoding A-type lamins are associated with a
      spectrum of predominantly tissue-specific diseases known as laminopathies.
      Linking the disease phenotypes to cellular functions of lamins has been a major
      challenge. Drosophila is being used as a model system to identify the roles of
      lamins in development. Towards this end, we performed a comparative study of
      Drosophila and human A-type lamins. Analysis of transgenic flies showed that
      human lamins localize predictably within the Drosophila nucleus. Consistent with
      this finding, yeast two-hybrid data demonstrated conservation of partner-protein
      interactions. Drosophila lacking A-type lamin show nuclear envelope defects
      similar to those observed with human laminopathies. Expression of mutant forms of
      the A-type Drosophila lamin modeled after human disease-causing amino acid
      substitutions revealed an essential role for the N-terminal head and the Ig-fold
      in larval muscle tissue. This tissue-restricted sensitivity suggests a conserved
      role for lamins in muscle biology. In conclusion, we show that (1) localization
      of A-type lamins and protein-partner interactions are conserved between
      Drosophila and humans, (2) loss of the Drosophila A-type lamin causes nuclear
      defects and (3) muscle tissue is sensitive to the expression of mutant forms of A
      type lamin modeled after those causing disease in humans. These studies provide
      new insights on the role of lamins in nuclear biology and support Drosophila as a
      model for studies of human laminopathies involving muscle dysfunction.

PMID- 19855838
TI  - Enhanced Edar signalling has pleiotropic effects on craniofacial and cutaneous
      glands.
AB  - The skin carries a number of appendages, including hair follicles and a range of
      glands, which develop under the influence of EDAR signalling. A gain of function
      allele of EDAR is found at high frequency in human populations of East Asia, with
      genetic evidence suggesting recent positive selection at this locus. The derived
      EDAR allele, estimated to have reached fixation more than 10,000 years ago,
      causes thickening of hair fibres, but the full spectrum of phenotypic changes
      induced by this allele is unknown. We have examined the changes in glandular
      structure caused by elevation of Edar signalling in a transgenic mouse model. We
      find that sebaceous and Meibomian glands are enlarged and that salivary and
      mammary glands are more elaborately branched with increased Edar activity, while
      the morphology of eccrine sweat and tracheal submucosal glands appears to be
      unaffected. Similar changes to gland sizes and structures may occur in human
      populations carrying the derived East Asian EDAR allele. As this allele attained
      high frequency in an environment that was notably cold and dry, increased
      glandular secretions could represent a trait that was positively selected to
      achieve increased lubrication and reduced evaporation from exposed facial
      structures and upper airways.

PMID- 19855839
TI  - Functional structure of spontaneous sleep slow oscillation activity in humans.
AB  - BACKGROUND: During non-rapid eye movement (NREM) sleep synchronous neural
      oscillations between neural silence (down state) and neural activity (up state)
      occur. Sleep Slow Oscillations (SSOs) events are their EEG correlates. Each event
      has an origin site and propagates sweeping the scalp. While recent findings
      suggest a SSO key role in memory consolidation processes, the structure and the
      propagation of individual SSO events, as well as their modulation by sleep stages
      and cortical areas have not been well characterized so far. METHODOLOGY/PRINCIPAL
      FINDINGS: We detected SSO events in EEG recordings and we defined and measured a
      set of features corresponding to both wave shapes and event propagations. We
      found that a typical SSO shape has a transition to down state, which is steeper
      than the following transition from down to up state. We show that during SWS SSOs
      are larger and more locally synchronized, but less likely to propagate across the
      cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as
      their amplitudes and slopes, are greatest in the frontal regions. Although
      derived from a small sample, this characterization provides a preliminary
      reference about SSO activity in healthy subjects for 32-channel sleep recordings.
      CONCLUSIONS/SIGNIFICANCE: This work gives a quantitative picture of spontaneous
      SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep
      stage, site of origin and detection location of the waves. Our measures on SSOs
      shape indicate that, as in animal models, onsets of silent states are more
      synchronized than those of neural firing. The differences between sleep stages
      could be related to the reduction of arousal system activity and to the breakdown
      of functional connectivity. The frontal SSO prevalence could be related to a
      greater homeostatic need of the heteromodal association cortices.

PMID- 19855840
TI  - Identification of miRNAs in a liver of a human fetus by a modified method.
AB  - BACKGROUND: miRNAs are 17-25 nucleotides long RNA molecules that have been found
      to regulate gene expression in human cells. There are studies showing that
      different groups of miRNAs are involved in development of different tissues. In
      hepatocytes there are reported particular types of miRNAs that regulate gene
      expression. METHODS: We established a human fetal liver cDNA library by a
      modified cloning protocol. Then plasmid isolation from the colonies was
      performed. After sequencing and database searching, the miRNAs were recognized.
      RT-PCR and sequencing were carried out to validate the miRNAs detected. Real-time
      PCR was used to analyze the expression of each miRNA. RESULTS: One novel miRNA
      was discovered, together with another 35 previously-known miRNAs in the fetal
      liver. Some of them existed in variants. The miRNAs identified were validated by
      RT-PCR and sequencing. Quantitative analysis showed that they have variable
      expression. CONCLUSION: Our results indicate that a special group of miRNAs may
      play an important role in fetal liver development in a synergistic manner.

PMID- 19855841
TI  - A NMDA receptor antagonist, MK-801 impairs consolidating extinction of auditory
      conditioned fear responses in a Pavlovian model.
AB  - BACKGROUND: In auditory fear conditioning, repeated presentation of the tone in
      the absence of shock leads to extinction of the acquired fear responses. The
      glutamate N-methyl-D-aspartate receptor (NMDAR) is thought to be involved in the
      extinction of the conditioned fear responses, but its detailed role in initiating
      and consolidating or maintaining the fear extinction memory is unclear. Here we
      investigated this issue by using a NMDAR antagonist, MK-801. METHODS/MAIN
      FINDINGS: The effects of immediate (beginning at 10 min after the conditioning)
      and delayed (beginning at 24 h after conditioning) extinctions were first
      compared with the finding that delayed extinction caused a better and long
      lasting (still significant on the 20(th) day after extinction) depression on the
      conditioned fear responses. In a second experiment, MK-801 was intraperitoneally
      (i.p.) injected at 40 min before, 4 h or 12 h after the delayed extinction,
      corresponding to critical time points for initiating, consolidating or
      maintaining the fear extinction memory. i.p. injection of MK-801 at either 40 min
      before or 4 h after delayed extinction resulted in an impairment of initiating
      and consolidating fear extinction memory, which caused a long lasting increased
      freezing score that was still significant on the 7th day after extinction,
      compared with extinction group. However, MK-801 administered at 12 h after the
      delayed extinction, when robust consolidation has been occurred and stabilized,
      did not affect the established extinction memory. Furthermore, the changed
      freezing behaviors was not due to an alteration in general anxiety levels, since
      MK-801 treatment had no effect on the percentage of open-arm time or open-arm
      entries in an Elevated Plus Maze (EPM) task. CONCLUSIONS/SIGNIFICANCE: Our data
      suggested that the activation of NMDARs plays important role in initiation and
      consolidation but not maintenance of fear extinction memory. Together with the
      fact that NMDA receptor is very important for memory, our data added experimental
      evidence to the concept that the extinction of conditioned fear responses is a
      procedure of initiating and consolidating new memory other than simply "erasing"
      the fear memory.

PMID- 19855842
TI  - Massive fluid requirements and an unusual BUN/creatinine ratio for pre-renal
      failure in patients with cholera.
AB  - BACKGROUND: Cholera is an important infectious cause of secretory diarrhea. The
      primary symptom of infection is the sudden onset of watery diarrhea with
      subsequent volume depletion causing renal insufficiency. The objective of this
      research is to study the level of dehydration at presentation and subsequent
      fluid management in patients with cholera. METHODS: This study was conducted on
      191 patients of Cholera admitted at a tertiary care hospital in Karachi, Pakistan
      during the period of 5 years. Medical charts were evaluated retrospectively for
      initial hydration status, baseline lab investigations on admission and discharge
      and fluid therapy given to all the patients while their stay in the hospital and
      the data was analyzed on SPSS 15.0. RESULTS: Out of the 191 patients, 83(43%)
      were males and 108 (57%) were females with mean age of 42.3 years (SD+/-18.34).
      The average duration of symptoms was 3.75 days (SD+/-2.04). Of 191 patients, 175
      (92.1%) presented with dehydration, 80 (42.3%) were given Ringer's Lactate (R/L)
      + Normal Saline (N/S), 45 (24%) patients were given R/L + N/S + Oral Rehydration
      Therapy (ORS), 27 (14.3%) of the patients were kept on R/L only and remaining
      were given various combinations of R/L, N/S, ORS and Dextrose Saline (D/S). On
      admission mean Blood Urea Nitrogen (BUN) was 24.54 (SD+/-16.6), mean creatinine
      was 2.47 (SD+/-2.35) and mean BUN/Creatinine ratio was 11.63 (SD+/-5.7).
      CONCLUSION: Aggressive fluid rehydration remains the cornerstone of management of
      cholera. Instead of presenting with a classical BUN/Creatinine ratio of >20:1,
      patients with pre-renal failure in cholera may present with a BUN/Creatinine
      ratio of <15:1.

PMID- 19855844
TI  - miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression
      in mice.
AB  - BACKGROUND: Micro RNAs are small, non-coding, single-stranded RNAs that
      negatively regulate gene expression at the post-transcriptional level. Since miR
      143 was found to be down-regulated in prostate cancer cells, we wanted to analyze
      its expression in human prostate cancer, and test the ability of miR-43 to arrest
      prostate cancer cell growth in vitro and in vivo. RESULTS: Expression of miR-143
      was analyzed in human prostate cancers by quantitative PCR, and by in situ
      hybridization. miR-143 was introduced in cancer cells in vivo by electroporation.
      Bioinformatics analysis and luciferase-based assays were used to determine miR
      143 targets. We show in this study that miR-143 levels are inversely correlated
      with advanced stages of prostate cancer. Rescue of miR-143 expression in cancer
      cells results in the arrest of cell proliferation and the abrogation of tumor
      growth in mice. Furthermore, we show that the effects of miR-143 are mediated, at
      least in part by the inhibition of extracellular signal-regulated kinase-5 (ERK5)
      activity. We show here that ERK5 is a miR-143 target in prostate cancer.
      CONCLUSIONS: miR-143 is as a new target for prostate cancer treatment.

PMID- 19855843
TI  - Gene responses to oxygen availability in Kluyveromyces lactis: an insight on the
      evolution of the oxygen-responding system in yeast.
AB  - The whole-genome duplication (WGD) may provide a basis for the emergence of the
      very characteristic life style of Saccharomyces cerevisiae-its fermentation
      oriented physiology and its capacity of growing in anaerobiosis. Indeed, we found
      an over-representation of oxygen-responding genes in the ohnologs of S.
      cerevisiae. Many of these duplicated genes are present as
      aerobic/hypoxic(anaerobic) pairs and form a specialized system responding to
      changing oxygen availability. HYP2/ANB1 and COX5A/COX5B are such gene pairs, and
      their unique orthologs in the 'non-WGD' Kluyveromyces lactis genome behaved like
      the aerobic versions of S. cerevisiae. ROX1 encodes a major oxygen-responding
      regulator in S. cerevisiae. The synteny, structural features and molecular
      function of putative KlROX1 were shown to be different from that of ROX1. The
      transition from the K. lactis-type ROX1 to the S. cerevisiae-type ROX1 could link
      up with the development of anaerobes in the yeast evolution. Bioinformatics and
      stochastic analyses of the Rox1p-binding site (YYYATTGTTCTC) in the upstream
      sequences of the S. cerevisiae Rox1p-mediated genes and of the K. lactis
      orthologs also indicated that K. lactis lacks the specific gene system responding
      to oxygen limiting environment, which is present in the 'post-WGD' genome of S.
      cerevisiae. These data suggested that the oxygen-responding system was born for
      the specialized physiology of S. cerevisiae.

PMID- 19855846
TI  - Hypothermia and postconditioning after cardiopulmonary resuscitation reduce
      cardiac dysfunction by modulating inflammation, apoptosis and remodeling.
AB  - BACKGROUND: Mild therapeutic hypothermia following cardiac arrest is
      neuroprotective, but its effect on myocardial dysfunction that is a critical
      issue following resuscitation is not clear. This study sought to examine whether
      hypothermia and the combination of hypothermia and pharmacological
      postconditioning are cardioprotective in a model of cardiopulmonary resuscitation
      following acute myocardial ischemia. METHODOLOGY/PRINCIPAL FINDINGS: Thirty pigs
      (28-34 kg) were subjected to cardiac arrest following left anterior descending
      coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2
      minutes of basic life support, advanced cardiac life support was started
      according to the current AHA guidelines. After successful return of spontaneous
      circulation (n = 21), coronary perfusion was reestablished after 60 minutes of
      occlusion, and animals were randomized to either normothermia at 38 degrees C,
      hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with
      sevoflurane (each group n = 7) for 24 hours. The effects on cardiac damage
      especially on inflammation, apoptosis, and remodeling were studied using cellular
      and molecular approaches. Five animals were sham operated. Animals treated with
      hypothermia had lower troponin T levels (p<0.01), reduced infarct size (34+/-7
      versus 57+/-12%; p<0.05) and improved left ventricular function compared to
      normothermia (p<0.05). Hypothermia was associated with a reduction in: (i) immune
      cell infiltration, (ii) apoptosis, (iii) IL-1beta and IL-6 mRNA up-regulation,
      and (iv) IL-1beta protein expression (p<0.05). Moreover, decreased matrix
      metalloproteinase-9 activity was detected in the ischemic myocardium after
      treatment with mild hypothermia. Sevoflurane conferred additional protective
      effects although statistic significance was not reached.
      CONCLUSIONS/SIGNIFICANCE: Hypothermia reduced myocardial damage and dysfunction
      after cardiopulmonary resuscitation possible via a reduced rate of apoptosis and
      pro-inflammatory cytokine expression.

PMID- 19855845
TI  - Regulation of GABA(A) and glutamate receptor expression, synaptic facilitation
      and long-term potentiation in the hippocampus of prion mutant mice.
AB  - BACKGROUND: Prionopathies are characterized by spongiform brain degeneration,
      myoclonia, dementia, and periodic electroencephalographic (EEG) disturbances. The
      hallmark of prioniopathies is the presence of an abnormal conformational isoform
      (PrP(sc)) of the natural cellular prion protein (PrP(c)) encoded by the Prnp
      gene. Although several roles have been attributed to PrP(c), its putative
      functions in neuronal excitability are unknown. Although early studies of the
      behavior of Prnp knockout mice described minor changes, later studies report
      altered behavior. To date, most functional PrP(c) studies on synaptic plasticity
      have been performed in vitro. To our knowledge, only one electrophysiological
      study has been performed in vivo in anesthetized mice, by Curtis and coworkers.
      They reported no significant differences in paired-pulse facilitation or LTP in
      the CA1 region after Schaffer collateral/commissural pathway stimulation.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we explore the role of PrP(c) expression in
      neurotransmission and neural excitability using wild-type, Prnp -/- and PrP(c)
      overexpressing mice (Tg20 strain). By correlating histopathology with
      electrophysiology in living behaving mice, we demonstrate that both Prnp -/- mice
      but, more relevantly Tg20 mice show increased susceptibility to KA, leading to
      significant cell death in the hippocampus. This finding correlates with enhanced
      synaptic facilitation in paired-pulse experiments and hippocampal LTP in living
      behaving mutant mice. Gene expression profiling using Illumina microarrays and
      Ingenuity pathways analysis showed that 129 genes involved in canonical pathways
      such as Ubiquitination or Neurotransmission were co-regulated in Prnp -/- and
      Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that
      subunits of GABA(A) and AMPA-kainate receptors are co-regulated in both Prnp -/-
      and Tg20 mice. CONCLUSIONS/SIGNIFICANCE: Present results demonstrate that PrP(c)
      is necessary for the proper homeostatic functioning of hippocampal circuits,
      because of its relationships with GABA(A) and AMPA-Kainate neurotransmission. New
      PrP(c) functions have recently been described, which point to PrP(c) as a target
      for putative therapies in Alzheimer's disease. However, our results indicate that
      a "gain of function" strategy in Alzheimer's disease, or a "loss of function" in
      prionopathies, may impair PrP(c) function, with devastating effects. In
      conclusion, we believe that present data should be taken into account in the
      development of future therapies.

PMID- 19855847
TI  - Safety and immunogenicity of the malaria vaccine candidate MSP3 long synthetic
      peptide in 12-24 months-old Burkinabe children.
AB  - BACKGROUND: A Phase Ia trial in European volunteers of the candidate vaccine
      merozoite surface protein 3 (MSP3), a Plasmodium falciparum blood stage membrane,
      showed that it induces biologically active antibodies able to achieve parasite
      killing in vitro, while a phase Ib trial in semi-immune adult volunteers in
      Burkina Faso confirmed that the vaccine was safe. The aim of this study was to
      assess the safety and immunogenicity of this vaccine candidate in children aged
      12-24 months living in malaria endemic area of Burkina Faso. METHODS: The study
      was a double-blind, randomized, controlled, dose escalation phase Ib trial,
      designed to assess the safety, reactogenicity and immunogenicity of three doses
      of either 15 or 30 microg of MSP3-LSP adsorbed on aluminum hydroxide in 45
      children 12 to 24 months of age randomized into three equal groups. Each group
      received 3 vaccine doses (on days 0, 28 and 56) of either 15 microg of MSP3-LSP,
      30 microg of MSP3-LSP or of the Engerix B hepatitis B vaccine. Children were
      visited at home daily for the 6 days following each vaccination to solicit
      symptoms which might be related to vaccination. Serious adverse events occurring
      during the study period (1 year) were recorded. Antibody responses to MSP3-LSP
      were measured on days 0, 28, 56 and 84. RESULTS: All 45 enrolled children
      received three MSP3 vaccine doses. No serious adverse events were reported. Most
      of the adverse events reported were mild to moderate in severity. The only
      reported local symptoms with grade 3 severity were swelling and induration, with
      an apparently dose related response. All grade 3 adverse events resolved without
      any sequelae. Both MSP3 doses regimens were able to elicit high levels of anti
      MSP3 specific IgG1 and IgG3 antibodies in the volunteers with very little or no
      increase in IgG2, IgG4 and IgM classes: i.e. vaccination induced predominantly
      the isotypes involved in the monocyte-dependent mechanism of P. falciparum
      parasite-killing. CONCLUSION: Our results support the promise of MSP3-LSP as a
      malaria vaccine candidate, both in terms of tolerability and of immunogenicity.
      Further assessment of the efficacy of this vaccine is recommended. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00452088.

PMID- 19855848
TI  - Consideration of shared decision making in nursing: a review of clinicians'
      perceptions and interventions.
AB  - As the number of individuals with chronic illness increases so has the need for
      strategies to enable nurses to engage them effectively in daily management of
      their conditions. Shared decision making between patients and nurses is one
      approach frequently discussed in the literature. This paper reviews recent
      studies of shared decision making and the meaning of findings for the nurse
      patient relationship. Patients likely to prefer to engage in shared decision
      making are younger and have higher levels of education. However, there is a lack
      of evidence for the effect of shared decision making on patient outcomes.
      Further, studies are needed to examine shared decision making when the patient is
      a child. Nurses are professionally suited to engage their patients fully in
      treatment plans. More evidence for how shared decision making affects outcomes
      and how nurses can successfully achieve such engagement is needed.

PMID- 19855850
TI  - The Relation Between Cognitive Development and Anxiety Phenomena in Children.
AB  - We examined the relation between cognitive development and fear, anxiety, and
      behavioral inhibition in a non-clinical sample of 226 Dutch children aged 4-9
      years. To assess cognitive development, children were tested with Piagetian
      conservation tasks and a Theory-of-Mind (TOM) test. Fears were measured by means
      of a self-report scale completed by the children, while anxiety symptoms and
      behavioral inhibition were indexed by rating scales that were filled out by
      parents. Significant age trends were observed for some anxiety phenomena. For
      example, younger children displayed higher fear scores, whereas older children
      exhibited higher levels of generalized anxiety. Most importantly, results of
      regression analyses (in which we controlled for age) indicated that cognitive
      development, and in particular TOM ability, made a unique and significant
      contribution to various domains of behavioral inhibition. In all cases, higher
      levels of TOM were associated with lower levels of behavioral inhibition. In
      general, percentages of explained variance were rather small (i.e., <6%),
      indicating that the role of cognitive development in various anxiety phenomena is
      limited.

PMID- 19855849
TI  - Integration of HIV-1 DNA is regulated by interplay between viral rev and cellular
      LEDGF/p75 proteins.
AB  - The present work describes a novel interaction between the human immunodeficiency
      virus type 1 (HIV-1) Rev protein and the cellular lens epithelium-derived growth
      factor p75 (LEDGF/p75) protein in vitro and in virus-infected cells. Here we
      show, for the first time, that formation of an Rev-LEDGF/p75 complex is a crucial
      step in regulating viral cDNA integration. Coimmunoprecipitation experiments at
      various times after virus infection revealed that, first, an integrase enzyme
      (IN)-LEDGF/p75 complex is formed, which is then replaced by a Rev-LEDGF/p75 and
      Rev-IN complexes. This was supported by in vitro experiments showing that Rev
      promotes dissociation of the IN-LEDGF/p75 complex. Combination of the viral IN
      and the cellular LEDGF/p75 is required for proper integration of the viral cDNA
      into the host chromosomal DNA. Our findings demonstrate that integration of HIV-1
      cDNA is regulated by an interplay between viral Rev and the host-cell LEDGF/p75
      proteins.

PMID- 19855851
TI  - Folate-mediated Cell Uptake of Shell-crosslinked Spheres and Cylinders.
AB  - This paper reports the synthesis of shell crosslinked nanoparticles (SCKs) of
      spherical and cylindrical shapes, and their functionalization with folate using a
      poly(ethylene glycol) (PEG) construct that has folate and an amine group as the
      opposing chain termini. By use of confocal microscopy, we demonstrate the
      selective delivery of folate conjugated SCKs to human KB cells, a cell line that
      overexpresses the folate receptor (FR). A higher extent of polymer uptake by the
      cells occurred with the cylindrical SCK morphology, relative to the spherical
      SCKs, when both samples had the same fluorescein-5-thiosemicarbazide and polymer
      concentrations. In both cases, by using excess free folic acid as a block or SCKs
      lacking the folate-PEG conjugate, cell uptake was significantly reduced. These
      results suggest that particle shape may play an important role in receptor
      mediated cell uptake, and may be exploited in the targeted delivery of nanoscopic
      drugs.

PMID- 19855852
TI  - Synthesis of Homopolymers and Copolymers Containing an Active Ester of Acrylic
      Acid by RAFT: Scaffolds for Controlling Polyvalent Ligand Display.
AB  - We describe the synthesis of activated homopolymers and copolymers of controlled
      molecular weight based on the controlled radical polymerization of N
      acryloyloxysuccinimide (NAS) by reversible addition fragmentation chain transfer
      (RAFT). We synthesized activated homopolymers in a range of molecular weights
      with polydispersities between 1 and 1.2. The attachment of an inhibitory peptide
      to the activated polymer backbone yielded a potent controlled molecular weight
      polyvalent inhibitor of anthrax toxin. To provide greater control over the
      placement of the peptides along the polymer backbone, we also used a semi-batch
      copolymerization method to synthesize copolymers of NAS and acrylamide (AAm).
      This approach enabled the synthesis of copolymers with control over the placement
      of peptide-reactive NAS monomers along an inert backbone; subsequent
      functionalization of NAS with peptide yielded well-defined polyvalent anthrax
      toxin inhibitors that differed in their potencies. These strategies for
      controlling molecular weight, ligand density, and ligand placement will be
      broadly applicable for designing potent polyvalent inhibitors for a variety of
      pathogens and toxins, and for elucidating structure-activity relationships in
      these systems.

PMID- 19855853
TI  - (Meth)Acrylate Vinyl Ester Hybrid Polymerizations.
AB  - In this study vinyl ester monomers were synthesized by an amine catalyzed Michael
      addition reaction between a multifunctional thiol and the acrylate double bond of
      vinyl acrylate. The copolymerization behavior of both methacrylate/vinyl ester
      and acrylate/vinyl ester systems was studied with near-infrared spectroscopy. In
      acrylate/vinyl ester systems, the acrylate groups polymerize faster than the
      vinyl ester groups resulting in an overall conversion of 80% for acrylate double
      bonds in the acrylate/vinyl ester system relative to only 50% in the bulk
      acrylate system. In the methacrylate/vinyl ester systems, the difference in
      reactivity is even more pronounced resulting in two distinguishable
      polymerization regimes, one dominated by methacrylate polymerization and a second
      dominated by vinyl ester polymerization. A faster polymerization rate and higher
      overall conversion of the methacrylate double bonds is thus achieved relative to
      polymerization of the pure methacrylate system. The methacrylate conversion in
      the methacrylate/vinyl ester system is near 100% compared to only ~60% in the
      pure methacrylate system. Utilizing hydrophilic vinyl ester and hydrophobic
      methacrylate monomers, polymerization-induced phase separation is observed. The
      phase separated domain size is on the order of ~1 MUm under the polymerization
      conditions. The phase separated domains become larger and more distinct with
      slower polymerization and correspondingly increased time for diffusion.

PMID- 19855854
TI  - On-Probe Pyrolysis Desorption Electrospray Ionization (DESI) Mass Spectrometry
      for the Analysis of Non-Volatile Pyrolysis Products.
AB  - An on-probe pyrolyzer has been constructed and interfaced with Desorption
      Electrospray Ionization (DESI) Mass Spectrometry (MS) for the rapid analysis of
      non-volatile pyrolysis products. The detection and analysis of non-volatile
      pyrolysis products of peptides, proteins and the synthetic polymer poly(ethylene
      glycol) are demonstrated with this instrument. The on-probe pyrolyzer can be
      operated off-line or on-line with the DESI source and was interfaced with a
      tandem MS (MS/MS) instrument, which allowed for structure characterization of the
      non-volatile pyrolytic products. Advantages of this system are its simplicity and
      speed of analysis since the pyrolysis is performed in situ on the DESI source
      probe and hence, it avoids extraction steps and/or the use of matrices (e.g., as
      in MALDI-MS analyses).

PMID- 19855855
TI  - Trajectories of Failure: The Educational Careers of Children with Mental Health
      Problems.
AB  - The authors draw on developmental psychopathology, life course sociology, and
      scholarship on educational processes to develop a conceptual framework for
      understanding the association of children's mental health problems with
      educational attainment. They use this framework to address two empirical gaps in
      prior research: lack of attention to mental health trajectories and the failure
      to consider diverse explanations. Using data from the Children of the National
      Longitudinal Surveys of Youth data set, the authors identify latent classes that
      characterize trajectories of internalizing and externalizing problems from
      childhood through adolescence. Youths in the classes vary significantly in their
      likelihoods of high school completion and college entry. The authors evaluate the
      ability of three sets of mediators to explain these patterns: academic aptitude,
      disruptive behaviors, and educational expectations. Educational expectations are
      important mediators independent of academic aptitude and disruptive behaviors.
      Social responses to youths' mental health problems contribute importantly to
      their disrupted educational trajectories.

PMID- 19855856
TI  - Driving on antidepressants: cruising for a crash?
AB  - Antidepressants are commonly prescribed medications that carry an imprecise risk
      of driving impairment. In this edition of The Interface, we explore the
      relationship between antidepressant medications and driving impairment. We
      conclude that while there may be a small risk of driving impairment with these
      medications, this risk is considerably heightened under particular clinical
      conditions. These conditions include the advanced age of the driver, initial
      dosing and start-up of the antidepressant, rapid escalation of antidepressant
      doses, high-dose antidepressants, presence of active and severe depressive
      symptoms (i.e., the antidepressant is merely functioning as a pharmacological
      marker for severe depressive illness), and/or coadministration of other
      psychotropic medications, especially benzodiazepines. Clinicians need to be
      mindful of these specific clinical conditions when prescribing antidepressants to
      patients.

PMID- 19855857
TI  - Adolescent depression: an update and guide to clinical decision making.
AB  - Depression in adolescence and adulthood is common, afflicting up to 20 percent of
      these populations. It represents a significant public health concern and is
      associated with considerable suffering and functional impairment. Adolescent
      onset depression tends to be a particularly malignant and recalcitrant condition,
      increasing the likelihood of recurrence and chronicity in adulthood. Clinical
      presentations for various medical and psychiatric conditions, as well as
      reactions to psychosocial stressors, can mimic or confound the picture of
      depression in adolescents. Therefore, careful assessment and differential
      diagnosis is essential. Effective treatments, both pharmacological and
      psychosocial in nature, exist, and so early detection and intervention is
      paramount. This article presents an overview of optimal prevention, assessment,
      and clinical decision-making strategies for managing depression in adolescents.

PMID- 19855858
TI  - Cranial Nerve II: Vision.
AB  - This article contains a brief review of the anatomy of the visual system, a
      survey of diseases of the retina, optic nerve and lesions of the optic chiasm,
      and other visual field defects of special interest to the psychiatrist. It also
      includes a presentation of the corticothalamic mechanisms, differential
      diagnosis, and various manifestations of visual illusions, and simple and complex
      visual hallucinations, as well as the differential diagnoses of these various
      visual phenomena.

PMID- 19855860
TI  - Music, medicine, healing, and the genome project.

PMID- 19855859
TI  - Sleep disorders in substance abusers: how common are they?
AB  - Substance abuse is a major public health problem with high morbidity and
      mortality. Comorbid disorders are suspected to cause a high relapse rate.
      Subjects with sleep disorders tend to self medicate with alcohol and
      tranquilizers to promote sleep or abuse stimulants to stay awake during the day.
      Substance abuse can, in turn, cause sleep disturbances, which can result in
      relapse. No studies have systematically studied the prevalence of various sleep
      disorders in these subjects. METHODS: This is a cross-sectional study conducted
      at the Alcohol and Drug Recovery Center (ADRC) at Cleveland Clinic, Cleveland,
      Ohio. Subjects with active substance abuse and the ability to consent were
      recruited to complete a comprehensive sleep disorder questionnaire, including a
      general medical, psychiatric, and substance abuse history as well as validated
      scales (e.g., Insomnia Severity Index, Pittsburgh Sleep Quality Index (PSQI),
      Berlin Questionnaire for sleep apnea and restless legs). RESULTS: Thirty patients
      completed the survey so far. The most commonly abused substance was alcohol (80%)
      followed by narcotics (40%); about 66 percent were polysubstance users. Forty-six
      percent of the patients reported using substance to self-medicate sleep problems.
      The prevalence of various sleep disorders in this population along with the
      prevalence in general population in parenthesis are as follows: Sleep impairment
      (PSQI>5) was noted in 96 percent (15%) of the subjects, and 56 percent (10-15%)
      had insomnia of moderate-to-severe degree. Symptoms suggestive of sleep apnea
      were reported in 53 percent (4-6%) of the subjects and restless leg syndrome
      symptoms in 33 percent (10%). CONCLUSION: Substance abuse is on the rise and
      affects every aspect of society. Our study has, for the first time,
      systematically evaluated various sleep disorders in these subjects who seem 5 to
      10 times more likely to have sleep disorders. Diagnosing and treating sleep
      disorders will have a huge impact in inducing remission. However, this study has
      significant limitations, including a small number of subjects, subjective data
      collected via questionnaires, and no long-term follow up, which makes it
      difficult to draw conclusions.

PMID- 19855861
TI  - The status of nutraceuticals for the treatment of depression.

PMID- 19855862
TI  - IMIA and its members: on balancing continuity and transition in biomedical and
      health informatics.
AB  - OBJECTIVE: To report on major past (2008) and future (2009 and beyond) activities
      of IMIA, the International Medical Informatics Association. METHOD: Summarizing
      discussions and planning activities within IMIA, in particular with respect to
      its Board and General Assembly meetings in 2008; looking at recent progress of
      biomedical and health informatics by commenting on IMIA Yearbook surveys and best
      paper selections. RESULTS: Major recent IMIA efforts include preparatory work for
      Medinfo 2010, global partnership activities in collaboration with WHO, planning
      activities for shifting to a biennial Medinfo cycle and setting up an IMIA
      office, all in accordance with IMIA's longterm strategic plan 'Towards IMIA
      2015'. The IMIA Yearbook of Medical Informatics, published annually since 1992,
      can be regarded as an important observatory for progress in health and biomedical
      informatics. Future activities include conference events in 2009 and IMIA's world
      congress, Medinfo 2010, finalizing a revision of IMIA's recommendations on
      education in biomedical and health informatics, and publication activities to
      stimulate the transfer of knowledge from theory to practice CONCLUSIONS: Since
      its inception in 1967, IMIA has evolved into a truly global organization, in a
      world where medical informatics has gained in significance and importance for
      supporting high-quality, efficient health care and for research in biomedicine
      and in the health sciences. Now in its 5th decade, IMIA's responsibilities, as
      well as opportunities, as a global, independent organization have both increased.
      Finding the right balance between continuity and transition, in order to
      appropriately support, stimulate, and, to some extent enable high-quality
      translational communication, research, education, and practice in biomedical and
      health informatics is a key IMIA challenge.

PMID- 19855863
TI  - In memoriam: Steven A. Huesing (1944-2009).

PMID- 19855865
TI  - Closing the loops in biomedical informatics.
AB  - OBJECTIVES: To provide an editorial introduction to the 2009 IMIA Yearbook of
      Medical Informatics with an overview of its contents and contributors. METHODS: A
      brief overview of the main theme, and an outline of the purposes, contents,
      format, and acknowledgment of contributions for the 2009 IMIA Yearbook. RESULTS:
      This 2009 issue of the IMIA Yearbook highlights important, beneficial loops
      which, if closed, could lead to considerable advances in the field of biomedical
      informatics and, indirectly, in healthcare and biomedical research. Progress
      towards closing the loops and remaining gaps are identified from the recent
      literature, illustrated by selected papers published during the past 12 months.
      CONCLUSION: Reviews and Surveys of the main research sub-fields in biomedical
      informatics in the Yearbook provide an overview of progress and current
      challenges across the spectrum of the discipline.

PMID- 19855866
TI  - Clinical decision support systems: the fascination with closed-loop control.

PMID- 19855867
TI  - STARE-HI -statement on reporting of evaluation studies in health informatics.
AB  - OBJECTIVE: Development of guidelines for publication of evaluation studies of
      Health Informatics applications. METHODS: An initial list of issues to be
      addressed in reports on evaluation studies was drafted based on experiences as
      editors and reviewers and as authors of systematic reviews , taking into account
      guidelines for reporting of medical research. This list has been discussed in
      several rounds by an increasing number of experts in Health Informatics
      evaluation during conferences and by using e-mail. RESULTS: A set of STARE-HI
      principles to be addressed in papers describing evaluations of Health Informatics
      interventions is presented. These principles include formulation of title and
      abstract, of introduction (e.g. scientific background, study objectives), study
      context (e.g. organizational setting, system details), methods (e.g. study
      design, outcome measures), results (e.g. study findings, unexpected observations)
      and discussion and conclusion. CONCLUSION: A comprehensive list of principles
      relevant for properly describing Health Informatics evaluations has been
      developed. When manuscripts submitted to Health Informatics journals and general
      medical journals adhere to these aspects, readers will be better positioned to
      place the studies in a proper context and judge their validity and
      generalisability. STARE-HI may also be used for study planning and hence
      positively influence the quality of evaluation studies in Health Informatics. We
      believe that better publication of (both quantitative and qualitative) evaluation
      studies is an important step toward the vision of evidence-based Health
      Informatics. LIMITATIONS: This study is based on experiences from editors,
      reviewers, authors of systematic reviews and readers of the scientific
      literature. The applicability of the principles has not been evaluated in real
      practice. Only when authors start to use these principles for reporting,
      shortcomings in the principles will emerge.

PMID- 19855868
TI  - "In the same boat": considerations on the partnership between healthcare
      providers and manufacturers of health IT products and medical devices.
AB  - OBJECTIVES: To assess the current culture of cooperation between healthcare
      providers (HCPs) and the healthcare industry (HCI) in the domain of Health-IT and
      Engineering (HITE) and identify possible strategies for improvement. METHODS:
      Based on reports in the literature and personal experience, major challenges were
      identified, the current ways of cooperation defined and their relation to each
      other analyzed. RESULTS: Four main challenges were identified for both sides
      involving: products and functionality, integration of IT-Systems with each other
      and with medical devices, usability, visions and strategic management. None of
      the four defined cooperation categories cover all aspects of the challenges, but
      cooperation in small, dedicated groups appeared to provide the most advantages.
      An increased participation of HCPs in standardization activities is crucial
      either directly or indirectly via professional or scientific organizations.
      CONCLUSIONS: Cooperation between provider management (hospitals, clinics or
      systems) and manufacturers of health IT products will be the key factor for
      success of the HCI while providing substantial benefits for providers. Both sides
      should invest heavily in such efforts.

PMID- 19855869
TI  - Closing the loops in biomedical informatics from theory to daily practice.
AB  - OBJECTIVES: This article presents the 2009 selection of the best papers in the
      special section dedicated to biomedical informatics and cybernetics. METHOD:
      Synopsis of the articles selected for the IMIA yearbook 2009 RESULTS: Five papers
      from international peer reviewed journals where selected for this section. Most
      of the papers have a strong practical orientation in clinical care. And this
      selection gives a good overview of what is done with "closing loop" approach,
      particularly during the year 2008. CONCLUSION: While quite mature for some
      clinical applications such as mechanical ventilation, it remains a challenge
      where rules for the decision system could be difficult to identify due to the
      number of variables. More complex systems with greater Artificial Intelligence
      approaches will certainly be the next trend for closed-loop applications.

PMID- 19855870
TI  - Electronic health record goes personal world-wide.
AB  - OBJECTIVE: Increasing patient demand for convenient access to their own
      healthcare data has led to more personal use of the Electronic Health Record
      (EHR). With "consumer empowerment" being an important issue of EHR, we are seeing
      a more "patient-centric" approach of EHR from countries around the world.
      Researchers have reported on issues in EHR sharing including concerns on privacy
      and security, consumer empowerment, competition among providers, and content
      standards. This study attempts to analyze prior research and to synthesize
      comprehensive, empirically-based conceptual models of EHR for personal use.
      METHODS: We use "B2C(2B) " to represent this new behavior of EHR sharing and
      exchange, with "consumer" in the center stage. RESULTS: Based on different
      information sharing mechanisms, we summarized the "B2C(2B) " behavior into three
      models, namely, the Inexpensive data media model, the Internet patient portal
      model and the Personal portable device model. Models each have their own
      strengths and weaknesses in their ways to share patient data and to address
      privacy and security concerns. CONCLUSION: Personal use of EHR under the B2C(2B)
      model does look promising based on our study. We started to observe a trend that
      governments around the world are embarking on related projects. With multiple
      stake-holders involved, we are only beginning to understand the complexity of
      such undertakings.

PMID- 19855871
TI  - Health and clinical management: from patient care to national public health
      increasing the integration of all health care participants and systems
      interoperability for better care management.
AB  - OBJECTIVES: To present some of last year's best papers in the field of health and
      clinical management. METHOD: Synopsis of the best articles selected for the IMIA
      Yearbook 2009. RESULTS: The selected articles illustrate how IT is enlarging its
      role in heath care management. By getting closer to patients allowing them
      feeding systems with there health data, IT can improve patient health management
      directly at patients' home. With data being documented in increasingly more
      structured and standardized way, health information systems can better integrated
      and reuse that data and offer more decision support to physicians and other
      health professionals. Furthermore, as more data is available in electronic format
      in real-time, entire populations' health status can be monitored by public health
      authorities allowing for better public health management. CONCLUSIONS: Although
      the selected articles are only a few bricks in global health management, they are
      promising examples of how IT improves the integration and collaboration between
      all participants in health care and offers support at all levels. Tying all these
      separate bricks together will still require work, as well as developing all the
      remain bricks, but systems interoperability allowing for data sharing and health
      participants collaboration are continuously getting more real.

PMID- 19855872
TI  - Current challenges and opportunities for better integration of human factors
      research with development of clinical information systems.
AB  - OBJECTIVES: Clinical information system (CIS) developers and implementers have
      begun to look to other scientific disciplines for new methods, tools, and
      techniques to help them better understand clinicians and their organizational
      structures, clinical work environments, capabilities of clinical information and
      communications technology, and the way these structures and processes interact.
      The goal of this article is to help CIS researchers, developers, implementers,
      and evaluators better understand the methods, tools, techniques, and literature
      of the field of human factors. METHODS: We developed a framework that explains
      how six key human factors topics relate to the design, implementation, and
      evaluation of CISs. RESULTS: Using this framework we discuss the following six
      topics: 1) informatics and patient safety; 2) user interface design and
      evaluation; 3) workflow and task analysis; 4) clinical decision making and
      decision support; 5) distributed cognition; and 6) mental workload and situation
      awareness. CONCLUSIONS: Integrating the methods, tools, and lessons learned from
      each of these six areas of human factors research early in CIS design and
      incorporating them iteratively during development can improve user performance,
      user satisfaction, and integration into clinical workflow. Ultimately, this
      approach will improve clinical information systems and healthcare delivery.

PMID- 19855873
TI  - A bio-medical informatics perspective on human factors understanding human
      factors influence in HIT-enabled institutions.
AB  - OBJECTIVES: To summarize current excellent research in the field of bio-medical
      informatics human factors. METHODS: We provide a synopsis of the articles
      selected for the IMIA yearbook 2009, from which we attempt to derive a synthetic
      overview of the activity and new trends in the field. A special attention was
      made to pick papers also from non bio-medical informatics specialized journals
      and to perform a worldwide selection. RESULTS: while the state of the research in
      the field of human factors is illustrated by a set of fairly heterogeneous
      studies, it is possible to identify trends. Thus, clearly, the importance of
      issues related to healthcare information technologies (HIT) adoption, still
      occupies a central role in the field. CONCLUSIONS: Convincing the clinicians of
      the HIT potential gains is still a challenge. But the HIT community will also
      have to give birth to interdisciplinary research and clear methods to optimize
      implementations and subsequent achievement of managerial objectives. The best
      paper selection of articles on human factors shows examples of excellent research
      on methods concerning original options to once again assess the importance of HIT
      and take into account the healthcare personnel psychology when confronted to the
      adoption of new tools and processes.

PMID- 19855874
TI  - Information systems in healthcare - state and steps towards sustainability.
AB  - OBJECTIVES: To identify core challenges and first steps on the way to sustainable
      information systems in healthcare. METHODS: Recent articles on healthcare
      information technology and related articles from Medical Informatics and Computer
      Science were reviewed and analyzed. Core challenges that couldn't be solved over
      the years are identified. RESULTS: The two core problem areas are process
      integration, meaning to effectively embed IT-systems into routine workflows, and
      systems integration, meaning to reduce the effort for interconnecting
      independently developed IT-components. Standards for systems integration have
      improved a lot, but their usefulness is limited where system evolution is needed.
      CONCLUSIONS: Sustainable Healthcare Information Systems should be based on system
      architectures that support system evolution and avoid costly system replacements
      every five to ten years. Some basic principles for the design of such systems are
      separation of concerns, loose coupling, deferred systems design, and service
      oriented architectures.

PMID- 19855875
TI  - Health information systems - new shifts and emerging trends in health IT
      infrastructures.
AB  - OBJECTIVES: Summarize excellent current research in the field of Health
      Information Systems. METHOD: Synopsis of the articles selected for the IMIA
      Yearbook 2009. RESULTS: Five papers from international peer reviewed journals
      have been selected for the section on health information systems. They
      concentrate on topics such as personal health records, the comparison of IT
      infrastructures in hospitals from different countries, hospital to hospital IT
      outsourcing partnership, and the wireless monitoring of patients. CONCLUSIONS:
      The elected articles highlight the new shifts in health information management
      and challenges faced by hospitals regarding IT infrastructures.

PMID- 19855876
TI  - Towards clinically available closed-loop systems for mechanical ventilation in
      the intensive care unit.
AB  - OBJECTIVE: To provide an overview of the state-of-the-art of closed-loop systems
      in the field of mechanical ventilation. METHODS: This survey is reviewing the
      literature and proposes an overview of existing closed-loop systems, in different
      areas of mechanical ventilation. It discusses the key points that guided their
      development and addresses specific issues such as their performance and
      penetration at the bedside. RESULTS: Much research has been undertaken in the
      hope of improving patient-ventilator interaction and shortening the weaning
      process. This led to the development of new modes of ventilation and expert
      weaning systems that are starting to achieve a wider clinical audience.
      CONCLUSION: Intensive care unit personnel are facing increasing work load during
      care for patients with severe, multi-system illness, using sophisticated
      equipment that generate high information flows requiring quick processing.
      Mechanical ventilation is a good example of a process that requires skillful and
      timely management of multiple parameters that could be delegated to closed-loop
      systems. Availability of commercial offerings, validated by randomized controlled
      trials in a well-defined set of clinical situations, is starting to fulfill the
      promise of intelligent systems skillfully assisting caregivers at the bedside.

PMID- 19855877
TI  - Sensors, medical images and signal processing: exploring multi-dimensional
      medical imaging data.
AB  - OBJECTIVES: To summarize current excellent research in the field of medical
      sensor, signal and imaging informatics. METHOD: Synopsis of the articles selected
      for the IMIA (International Medical Informatics Association) Yearbook 2009.
      RESULTS: Current research in the field of sensors, signal, and imaging
      informatics is characterized by theoretically sound techniques and evaluations
      with focus in imaging informatics. CONCLUSIONS: The best paper selection of
      articles on sensors, signal, and imaging informatics shows examples of excellent
      research on methods concerning theoretically sound original development in this
      field. Imaging and particularly multi-dimensional imaging has had in 2008 by far
      the largest number of publications compared to signals and sensors.

PMID- 19855878
TI  - The changing nature of clinical decision support systems: a focus on consumers,
      genomics, public health and decision safety.
AB  - OBJECTIVES: To review the recent research literature in clinical decision support
      systems (CDSS). METHODS: A review of recent literature was undertaken, focussing
      on CDSS evaluation, consumers and public health, the impact of translational
      bioinformatics on CDSS design, and CDSS safety. RESULTS: In recent years,
      researchers have concentrated much less on the development of decision
      technologies, and have focussed more on the impact of CDSS in the clinical world.
      Recent work highlights that traditional process measures of CDSS effectiveness,
      such as document relevance are poor proxy measures for decision outcomes.
      Measuring the dynamics of decision making, for example via decision velocity, may
      produce a more accurate picture of effectiveness. Another trend is the broadening
      of user base for CDSS beyond front line clinicians. Consumers are now a major
      focus for biomedical informatics, as are public health officials, tasked with
      detecting and managing disease outbreaks at a health system, rather than
      individual patient level. Bioinformatics is also changing the nature of CDSS.
      Apart from personalisation of therapy recommendations, translational
      bioinformatics is creating new challenges in the interpretation of the meaning of
      genetic data. Finally, there is much recent interest in the safety and
      effectiveness of computerised physician order entry (CPOE) systems, given that
      prescribing and administration errors are a significant cause of morbidity and
      mortality. Of note, there is still much controversy surrounding the contention
      that poorly designed, implemented or used CDSS may actually lead to harm.
      CONCLUSIONS: CDSS research remains an active and evolving area of research, as
      CDSS penetrate more widely beyond their traditional domain into consumer decision
      support, and as decisions become more complex, for example by involving sequence
      level genetic data.

PMID- 19855879
TI  - A medical informatics perspective on decision support: toward a unified research
      paradigm combining biological vs. clinical, empirical vs. legacy, and structured
      vs. unstructured data.
AB  - OBJECTIVES: To summarize current excellent research in the field of decision
      support systems. METHODS: We provide a synopsis of the articles selected for the
      IMIA Yearbook 2009, from which we attempt to derive a synthetic overview of the
      activity and new trends in the field. RESULTS: Five papers from international
      peer reviewed journals have been selected for the section on decision support.
      While the state of the research in the field of decision-support systems is
      illustrated by a set of fairly heterogeneous studies, it is possible to identify
      trends. Thus, issues related to guidelines processing implementation occupies a
      central role in today's field with two alternative directions: 1. broad medical
      applications, which attempts to assist decision-makers to process large patient
      sets; 2. narrow clinical applications focused on in-depth real-time signal
      processing for a specific population or medical specialty. CONCLUSIONS: The best
      paper selection of articles on decision-supports shows examples of excellent
      research on methods concerning original development as well as quality assurance
      of reported studies. It is also observed that this year's selection point
      directly to more original research areas such as temporal signal processing,
      although more traditionally related areas, such as information retrieval and/or
      natural language processing, remain fairly active in the field. Altogether these
      papers support the idea that more elaborated computer tools, likely to combine
      together textual and highly structured data, including real-time data contents,
      are needed.

PMID- 19855880
TI  - Knowledge representation and management: towards interoperable medical
      terminologies.
AB  - OBJECTIVES: To summarize current outstanding research in the field of knowledge
      representation and management. METHOD: Synopsis of the articles selected for the
      IMIA Yearbook 2009. RESULTS: Four excellent papers have been selected for the
      section knowledge representation and management. All these papers are concerned
      with terminological systems whether it is to detect equivalent concept
      definitions, to structure narratives, to compare existing lay and professional
      terms or to reformulate the SNOMED's logical formalism towards a more expressive
      language. CONCLUSIONS: The ability of one computer system to access and use the
      resources of another system becomes crucial in a world where the amount of
      electronically stored data increases continuously. The selected papers for the
      section knowledge representation and management corroborate that interoperable
      medical terminologies play a growing and strategic role in Electronic Health
      Record (EHR) systems. Indeed, they allow data in clinical systems to be defined
      in a more uniform and granular manner, thus leading to flexible, semantically
      interoperable and trust-worthy health information systems.

PMID- 19855881
TI  - Education, practice, and research in nursing terminology: gaps, challenges, and
      opportunities.
AB  - OBJECTIVES: To provide an overview of nursing terminology education, research,
      and clinical use, to identify and analyze any gaps therein, and to propose ways
      to close those gaps. METHODS: We conducted an extensive Internet and literature
      search to establish the current status of nursing terminology education,
      research, and clinical use. We also surveyed 40 experts in nursing terminology
      from 15 countries to obtain more detailed information on nursing terminology
      education and clinical use. RESULTS: We found that there are gaps in nursing
      terminology education, research, and use, with the area of research being the
      most advanced. Nursing terminology is not taught widely in either informatics or
      nursing programs. Where it is taught, it constitutes only up to several hours of
      an informatics or nursing course. Research into nursing terminology has been very
      active, focusing mainly on the development and evaluation/validation of nursing
      terminology, using reference terminology models, and mapping between these and
      nursing terminologies. However, little research has been carried out on the use
      of nursing terminologies in clinical information systems. In addition, there are
      very few systems in which a standardized nursing terminology has been
      implemented. CONCLUSION: In order to close the gaps in nursing terminology
      education, research, and clinical use, qualified personnel are required to
      educate potential users as to the importance of terminology-based information
      systems for semantic interoperability. In addition, more research is required
      into the implementation of nursing terminologies in information systems, and we
      must demonstrate the usefulness and effectiveness of nursing terminology-based
      information systems.

PMID- 19855882
TI  - Education and consumer informatics.
AB  - OBJECTIVES: This article presents the 2009 selection of the best papers
      presenting the advancements in the field of Education and Consumer Informatics
      with emphasis on quality online health information and its uses in the medical
      field. METHOD: Synopsis of the articles selected for the IMIA yearbook 2009
      RESULTS: Six papers from international peer reviewed journals where selected for
      this section. CONCLUSION: The selection of articles gives an overview of the
      currently growing need for quality online health information and demonstrates the
      integration of online health information in medical care as well as the
      importance of continuing education through online training programs.

PMID- 19855883
TI  - Ten thousand views of bioinformatics: a bibliome perspective.
AB  - OBJECTIVE: Summarize the current state bioinformatics research from the published
      literature in 2008. METHODS: The entire corpus of publications indexed by the
      National Library of Medicine in the PubMed repository was reviewed for articles
      tagged as belonging to the discipline of bioinformatics by Medical Subject
      Heading or by term in the title or abstract of the article. Selected summary
      statistics of this corpus were then used to motivate additional exploration.
      RESULTS: Over ten thousand articles published in 2008 populated the
      bioinformatics corpus. Significantly, there were at least as many publications in
      genomics and genetics that used computational techniques but that were not
      identified as bioinformatics research. Genomics and proteomics continued to be
      the leading application domains of bioinformatics research but despite the
      proliferation of human studies, the genes most studied in the corpus were from
      yeast rather than the human organism. The growth in the genomic studies of human
      disease was accompanied by a growing critical literature regarding the methods,
      results and impact of these studies. Concurrently, the availability of full
      genome sequences at commodity prices has increased the computational challenges
      of human studies by several orders of magnitude. Further concerns were raised
      about the consequences of public disclosure of comprehensive or even aggregate
      genomic data. CONCLUSION: The impressive size of the bioinformatics bibliome is
      easily dwarfed by the challenges generated by the continued increased growth of
      high-throughput biological data sets. The demand for bioinformatics expertise and
      tools is therefore likely to continue to increase, at least in the near term.

PMID- 19855884
TI  - Accelerating knowledge discovery through community data sharing and integration.
AB  - OBJECTIVES: To summarize current excellent research in the field of
      bioinformatics. METHOD: Synopsis of the articles selected for the IMIA Yearbook
      2009. RESULTS: The selection process for this yearbook's section on
      Bioinformatics results in six excellent articles highlighting several important
      trends First, it can be noted that Semantic Web technology continues to play an
      important role in heterogeneous data integration. Novel applications also put
      more emphasis on its ability to make logical inferences leading to new insights
      and discoveries. Second, translational research, due to its complex nature,
      increasingly relies on collective intelligence made available through the
      adoption of community-defined protocols or software architectures for secure data
      annotation, sharing and analysis. Advances in systems biology, bio-ontologies and
      text-ming can also be noted. CONCLUSIONS: Current biomedical research gradually
      evolves towards an environment characterized by intensive collaboration and more
      sophisticated knowledge processing activities. Enabling technologies, either
      Semantic Web or other solutions, are expected to play an increasingly important
      role in generating new knowledge in the foreseeable future.

PMID- 19855885
TI  - Clinical data mining: a review.
AB  - OBJECTIVE: Clinical data mining is the application of data mining techniques
      using clinical data. We review the literature in order to provide a general
      overview by identifying the status-of-practice and the challenges ahead. METHODS:
      The nine data mining steps proposed by Fayyad in 1996 [4] were used as the main
      themes of the review. MEDLINE was used as primary source and 84 papers were
      retained based on our inclusion criteria. RESULTS: Clinical data mining has three
      objectives: understanding the clinical data, assist healthcare professionals, and
      develop a data analysis methodology suitable for medical data. Classification is
      the most frequently used data mining function with a predominance of the
      implementation of Bayesian classifiers, neural networks, and SVMs (Support Vector
      Machines). A myriad of quantitative performance measures were proposed with a
      predominance of accuracy, sensitivity, specificity, and ROC curves. The latter
      are usually associated with qualitative evaluation. CONCLUSION: Clinical data
      mining respects its commitment to extracting new and previously unknown knowledge
      from clinical databases. More efforts are still needed to obtain a wider
      acceptance from the healthcare professionals and for generalization of the
      knowledge and reproducibility of its extraction process: better description of
      variables, systematic report of algorithm parameters including the method to
      obtain them, use of easy-to-understand models and comparisons of the efficiency
      of clinical data mining with traditional statistical analyses. More and more data
      will be available for data miners and they have to develop new methodologies and
      infrastructures to analyze the increasingly complex medical data.

PMID- 19855886
TI  - Biomedical informatics and the convergence of Nano-Bio-Info-Cogno (NBIC)
      technologies.
AB  - OBJECTIVES: To analyze the role that biomedical informatics could play in the
      application of the NBIC Converging Technologies in the medical field and raise
      awareness of these new areas throughout the Biomedical Informatics community.
      METHODS: Review of the literature and analysis of the reference documents in this
      domain from the biomedical informatics perspective. Detailing existing
      developments showing that partial convergence of technologies have already
      yielded relevant results in biomedicine (such as bioinformatics or biochips).
      Input from current projects in which the authors are involved is also used.
      RESULTS: Information processing is a key issue in enabling the convergence of
      NBIC technologies. Researchers in biomedical informatics are in a privileged
      position to participate and actively develop this new scientific direction. The
      experience of biomedical informaticians in five decades of research in the
      medical area and their involvement in the completion of the Human and other
      genome projects will help them participate in a similar role for the development
      of applications of converging technologies -particularly in nanomedicine.
      CONCLUSIONS: The proposed convergence will bring bridges between traditional
      disciplines. Particular attention should be placed on the ethical, legal, and
      social issues raised by the NBIC convergence. These technologies provide new
      directions for research and education in Biomedical Informatics placing a greater
      emphasis in multidisciplinary approaches.

PMID- 19855887
TI  - From ambient assisted living to global information management: IMIA-referencing
      publications in 2008.
AB  - OBJECTIVE: To give an overview of publications directly referencing the
      International Medical Informatics Association (IMIA) in 2008. METHOD: Systematic
      search for references to IMIA over the two official IMIA journals, and reports of
      the recent IMIA General Assembly and Board meetings, using PubMed/Medline,
      supplemented by searches with Google Scholar and Google Books. RESULTS: Beyond
      the IMIA Yearbook 2008, 38 IMIA-referencing publications were found by these
      searches, encompassing a broad range of topics, ranging from ambient assisted
      living technologies in home environments to global information management
      methodologies. CONCLUSIONS: In 2008 IMIA-referencing publications found through
      both medical and general search engines were predominantly in journals. In years
      where IMIA's world congress on medical informatics, Medinfo take place, it could
      be expected that the Medinfo proceedings will also play an important role in
      referencing IMIA explicitly.

PMID- 19855888
TI  - Spreading knowledge in medical informatics: the contribution of the hospital
      Italiano de Buenos Aires.
AB  - Medical Informatics (MI) is an emerging discipline with a high need of trained
      and skillful professionals. OBJECTIVE: To describe the educational experience of
      the Department of Health Informatics of the Hospital Italiano de Buenos Aires.
      METHODS: A descriptive study of the development of the Medical Informatics
      Residency Program (MIRP) and the e-learning courses related to medical
      informatics. RESULTS: A four-year MIRP with 15 rotations was started in 2000, and
      was awarded national educational accreditation. Eight residents have been fully
      trained and their main academic contributions are shown in this study. The e
      learning courses related to medical informatics (Healthcare Management,
      Epidemiology & Biostatistics, Information Retrieval, Computer Literacy started,
      10x10 Spanish version and HL7 introductory course) started in 2006 and were
      followed by more than 2266 students from all over the world, with an increase
      trend in foreign students. CONCLUSIONS: These educational activities have
      produced skilled human resources for the development and maintenance of the
      health informatics projects at our Hospital. In parallel, the number of students
      trained by e-learning continues to increase, demonstrating the worldwide need of
      knowledge in this field.

PMID- 19855889
TI  - Health information systems training for a countrywide implementation in Uruguay.
AB  - OBJECTIVES: Health Information systems training is one of the bottlenecks in
      clinical systems implementation. In this article, a strategy to massively create
      and train interdisciplinary coordinating teams is described for a project in
      Uruguay at FEMI, a non-academic setting which includes 23 health care
      institutions across the country and a tertiary referral center in Montevideo.
      METHODS: A series of educational activities were designed for the local
      coordinating teams. They included both onsite and online formats, site visits,
      integrated with some of the project tasks. RESULTS: In total, 128 professionals
      from all the Institutions participated in one or more of the training sessions
      (onsite and online) and 87 of them accomplished one of the forms of training.
      CONCLUSIONS: Massive basic health informatics training was possible in Uruguay
      through collaboration with academic institutions at the country and regional
      level. Next steps include an active involvement of nurses in the educational
      events and planning of massive training of end users.

PMID- 19855890
TI  - Health informatics education and capacity building in Eastern Cape Province,
      South Africa.
AB  - OBJECTIVES: To describe the experience of, and lessons learned from, a
      collaborative project developing and delivering an MSc in Health Informatics in
      South Africa. METHODS: The description and discussion is based on the experiences
      of the staff delivering the course, and formal and informal evaluations, the
      former conducted as part of the University of Winchester's quality assurance
      processes. RESULTS: Some of the lessons learned from adapting the course to meet
      local needs are described and discussed. CONCLUSIONS: Simply attempting to
      transpose a successful course from one country and culture to another is not a
      guarantee of success. Educational staff delivering such courses need to take
      account of local context and culture, be flexible and prepared to adapt to
      students' needs and circumstances, which may be beyond anyone's control. However,
      by meeting real identified needs, success can contribute to sustaining capacity
      building and the development of the local health informatics workforce.

PMID- 19855891
TI  - Informatics training for clinicians is more important than hardware and software.
AB  - OBJECTIVE: The importance of training physicians and nurses in the art, skill and
      science of clinical informatics has never been greater. What level of training is
      necessary and sufficient to equip the 21st century healthcare workforce for the
      transformative opportunity enabled by widespread deployment of EHRs? METHODS:
      Building on the success of its 10x10 program, AMIA with support from the Robert
      Wood Johnson foundation took its next step to create the necessary documents to
      have clinical informatics recognized as a sub-specialty by the American Board of
      Medical Specialties (ABMS). RESULTS: We defined the core content that had to be
      mastered and describing how physicians interested in the sub-specialty clinical
      informatics would be trained. The results of this work have been approved by the
      board of AMIA and have been published in its journal JAMIA. CONCLUSION: The
      health challenges of the 21 century require that we rapidly train the clinical
      workforce in clinical informatics. In addition to buying hardware and software,
      our health systems need to sponsor this training. Two percent of every Health IT
      budget should be targeted for clinician education.

PMID- 19855892
TI  - Imaging informatics: from image management to image navigation.
AB  - OBJECTIVE: To review the rapid evolution of imaging informatics dealing with
      issues of management and communication of digital images starting from the era of
      simple storage and transfer of images to today's world of interactive navigation
      in large sets of multidimensional data. METHODS: This paper will review the
      initial concepts of Picture Archiving and Communication Systems (PACS) and the
      early developments and standardization efforts that lead to the deployment of
      large intra-institutional networks of image distribution allowing radiologists
      and physicians to access and review images digitally. With the deployment of PACS
      came along the need for advanced tools for image visualization and image
      analysis. RESULTS: Review of the history of PACS and Imaging Informatics clearly
      shows that the early developments were focused on the radiologist's requirements
      for diagnosis and image interpretation. These early developments lagged behind
      the rapid adoption of digital imaging in areas outside radiology. Only recently,
      imaging informatics shifted toward the development of new tools geared toward the
      needs of other users such as surgeons, referring physicians and care-providers,
      and even for the patients themselves. Also in the recent years, the development
      of multimedia and communication tools in the consumer market has influenced the
      design and strategic development of image management platforms inside and outside
      healthcare institutions. CONCLUSIONS: The focus of imaging informatics has
      clearly shifted in the last decade from basic infrastructure design to complete
      data and image navigation systems. While the challenge of storing and managing
      large volumes of imaging data have slowly vanished with the rapid development if
      information technology, the new challenge emerged from the new requirements of
      image manipulation and analysis in clinical practice.

PMID- 19855900
TI  - Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the
      treatment of patients with schizophrenia: an update.
AB  - Growing consistent evidence indicates that hypofunction of N-methyl-D-aspartate
      (NMDA) transmission plays a pivotal role in the neuropathophysiology of
      schizophrenia. Hence, drugs which modulate NMDA neurotransmission are promising
      approaches to the treatment of schizophrenia. The aim of this article is to
      review clinical trials with novel compounds acting on the NMDA receptor (NMDA-R).
      This review also includes a discussion and translation of neuroscience into
      schizophrenia therapeutics. Although the precise mechanism of action of
      minocycline in the brain remains unclear, there is evidence that it blocks the
      neurotoxicity of NMDA antagonists and may exert a differential effect on NMDA
      signaling pathways. We, therefore, hypothesize that the effects of minocycline on
      the brain may be partially modulated by the NMDA-R or related mechanisms. Thus,
      we have included a review of minocycline neuroscience. The search was performed
      in the PubMed, Web of Science, SciELO, and Lilacs databases. The results of
      glycine and D-cycloserine trials were conflicting regarding effectiveness on the
      negative and cognitive symptoms of schizophrenia. D-serine and D-alanine showed a
      potential effect on negative symptoms and on cognitive deficits. Sarcosine data
      indicated a considerable improvement as adjunctive therapy. Finally, minocycline
      add-on treatment appears to be effective on a broad range of psychopathology in
      patients with schizophrenia. The differential modulation of NMDA-R neurosystems,
      in particular synaptic versus extrasynaptic NMDA-R activation and specific
      subtypes of NMDA-R, may be the key mediators of neurogenesis and neuroprotection.
      Thus, psychotropics modulating NMDA-R neurotransmission may represent future
      monotherapy or add-on treatment strategies in the treatment of schizophrenia.

PMID- 19855901
TI  - Dengue virus-induced regulation of the host cell translational machinery.
AB  - Dengue virus (DV)-induced changes in the host cell protein synthesis machinery
      are not well understood. We investigated the transcriptional changes related to
      initiation of protein synthesis. The human hepatoma cell line, HepG2, was
      infected with DV serotype 2 for 1 h at a multiplicity of infection of one. RNA
      was extracted after 6, 24 and 48 h. Microarray results showed that 36.5% of the
      translation factors related to initiation of protein synthesis had significant
      differential expression (Z-score >or= +/-2.0). Confirmation was obtained by
      quantitative real-time reverse transcription-PCR. Of the genes involved in the
      activation of mRNA for cap-dependent translation (eIF4 factors), eIF4A, eIF4G1
      and eIF4B were up-regulated while the negative regulator of translation eIF4E-BP3
      was down-regulated. This activation was transient since at 24 h post-infection
      levels were not significantly different from control cells. However, at 48 h post
      infection, eIF4A, eIF4E, eIF4G1, eIF4G3, eIF4B, and eIF4E-BP3 were down
      regulated, suggesting that cap-dependent translation could be inhibited during
      the progression of infection. To test this hypothesis, phosphorylation of p70S6K
      and 4E-BP1, which induce cap-dependent protein synthesis, was assayed. Both
      proteins remained phosphorylated when assayed at 6 h after infection, while
      infection induced dephosphorylation of p70S6K and 4E-BP1 at 24 and 48 h of
      infection, respectively. Taken together, these results provide biological
      evidence suggesting that in HepG2 cells DV sustains activation of the cap
      dependent machinery at early stages of infection, but progression of infection
      switches protein synthesis to a cap-independent process.

PMID- 19855902
TI  - Peritoneal and serum interleukin-18 levels are not increased in women with
      minimum or mild endometriosis.
AB  - Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 family.
      Endometriosis is strongly associated with sub-fertility, and affects about 15% of
      women of reproductive age. IL-18 may favor the progression of endometriosis. The
      objective of the present study was to determine the concentration of IL-18 in the
      serum and peritoneal fluid of infertile women with endometriosis. Forty infertile
      and 25 fertile women were screened in a teaching hospital. Thirty-four infertile
      patients with minimal or mild endometriosis and 22 fertile controls were enrolled
      in the study. The primary outcome was the estimate of IL-18 levels and the
      secondary outcome was the correlation between serum and peritoneal levels of IL
      18. There were no differences between the two groups regarding age, body mass
      index and levels of peritoneal fluid IL-18 (mean +/- SD): 290.85 +/- 173.02 pg/mL
      for infertile women vs 374.21 +/- 330.15 pg/mL for controls; or serum IL-18:
      391.07 +/- 119.71 pg/mL for infertile women vs 373.42 +/- 129.11 pg/mL for
      controls. However, a positive association was found between serum and peritoneal
      IL-18 levels in patients with endometriosis: r = 0.794, P = 0.0001. All
      measurements were carried out at the same time by the Human IL-18 Immuno Assay
      ELISA kit (MBL Co. Ltd., Japan). The present study did not find evidence
      supporting the hypothesis that IL-18 levels are associated with infertility in
      women with minimal and mild endometriosis, although a positive correlation was
      detected in these women between peritoneal and serum levels of IL-18.

PMID- 19855903
TI  - Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral
      striatum and prefrontal cortex of female rats repeatedly treated with cocaine.
AB  - Female rats are intensely affected by cocaine, with estrogen probably playing an
      important role in this effect. Progesterone modulates the GABA system and
      attenuates the effects of cocaine; however, there is no information about its
      relevance in changing GABA synthesis pathways after cocaine administration to
      female rats. Our objective was to investigate the influence of progesterone on
      the effects of repeated cocaine administration on the isoenzymes of glutamic acid
      decarboxylase (GAD(65) and GAD(67)) mRNA in brain areas involved in the addiction
      circuitry. Ovariectomized, intact and progesterone replacement-treated female
      rats received saline or cocaine (30 mg/kg, ip) acutely or repeatedly. GAD
      isoenzyme mRNA levels were determined in the dorsolateral striatum (dSTR) and
      prefrontal cortex (PFC) by RT-PCR, showing that repeated, but not acute, cocaine
      decreased GADs/beta-actin mRNA ratio in the dSTR irrespective of the hormonal
      condition (GAD(65): P < 0.001; and GAD(67): P = 0.004). In the PFC, repeated
      cocaine decreased GAD(65) and increased GAD(67) mRNA ratio (P < 0.05).
      Progesterone replacement decreased both GAD isoenzymes mRNA ratio after acute
      cocaine in the PFC (P < 0.001) and repeated cocaine treatment reversed this
      decrease (P < 0.001). These results suggest that cocaine does not immediately
      affect GAD mRNA expression, while repeated cocaine decreases both GAD(65) and
      GAD(67) mRNA in the dSTR of female rats, independently of their hormonal
      conditions. In the PFC, repeated cocaine increases the expression of GAD
      isoenzymes, which were decreased due to progesterone replacement.

PMID- 19855904
TI  - Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin
      sensitive afferent pathway.
AB  - Dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered iv and Dp
      administered icv delay gastric emptying (GE) in rats. The participation of
      capsaicin (Cps)-sensitive afferent fibers in this phenomenon was evaluated. Male
      Wistar rats were pretreated sc with Cps (50 mg/kg) or vehicle between the first
      and second day of life and both groups were submitted to the eye-wiping test. GE
      was determined in these animals at the age of 8/9 weeks (weight: 200-300 g). Ten
      minutes before the study, the animals of both groups were treated iv with Dp, AA
      or At (240 micromol/kg), or saline; or treated icv with Dp (4 micromol/animal) or
      saline. GE was determined 10 min after treatment by measuring % gastric retention
      (GR) of saline labeled with phenol red 10 min after orogastric administration.
      Percent GR (mean +/- SEM, N = 8) in animals pretreated with Cps and treated with
      Dp, AA or At (35.8 +/- 3.2, 35.4 +/- 2.2, and 35.6 +/- 2%, respectively) did not
      differ from the GR of saline-treated animals pretreated with vehicle (36.8 +/-
      2.8%) and was significantly lower than in animals pretreated with vehicle and
      treated with the drugs (52.1 +/- 2.8, 66.2 +/- 4, and 55.8 +/- 3%, respectively).
      The effect of icv administration of Dp (N = 6) was not modified by pretreatment
      with Cps (63.3 +/- 5.7%) compared to Dp-treated animals pretreated with vehicle
      (62.3 +/- 2.4%). The results suggest the participation of capsaicin-sensitive
      afferent fibers in the delayed GE induced by iv administration of Dp, AA and At,
      but not of icv Dp.

PMID- 19855905
TI  - Animal model for age- and sex-related genotoxicity of diethylstilbestrol.
AB  - Environmental xenoestrogens pose a significant health risk for all living
      organisms. There is growing evidence concerning the different susceptibility to
      xenoestrogens of developing and adult organisms, but little is known about their
      genotoxicity in pre-pubertal mammals. In the present study, we developed an
      animal model to test the sex- and age-specific genotoxicity of the synthetic
      estrogen diethylstilbestrol (DES) on the reticulocytes of 3-week-old pre-pubertal
      and 12-week-old adult BALB/CJ mice using the in vivo micronucleus (MN) assay. DES
      was administered intraperitoneally at doses of 0.05, 0.5, and 5 microg/kg for 3
      days and animals were sampled 48, 72 and 96 h, and 2 weeks after exposure. Five
      animals were analyzed for each dose, sex, and age group. After the DES dose of
      0.05 microg/kg, pre-pubertal mice showed a significant increase in MN frequency
      (P < 0.001), while adults continued to show reference values (5.3 vs 1.0 MN/1000
      reticulocytes). At doses of 0.5 and 5 microg/kg, MN frequency significantly
      increased in both age groups. In pre-pubertal male animals, MN frequency remained
      above reference values for 2 weeks after exposure. Our animal model for pre
      pubertal genotoxicity assessment using the in vivo MN assay proved to be
      sensitive enough to distinguish age and sex differences in genome damage caused
      by DES. This synthetic estrogen was found to be more genotoxic in pre-pubertal
      mice, males in particular. Our results are relevant for future investigations and
      the preparation of legislation for drugs and environmentally emitted agents,
      which should incorporate specific age and gender susceptibility.

PMID- 19855906
TI  - Glomerular filtration is reduced by high tidal volume ventilation in an in vivo
      healthy rat model.
AB  - Mechanical ventilation has been associated with organ failure in patients with
      acute respiratory distress syndrome. The present study examines the effects of
      tidal volume (V(T)) on renal function using two V T values (8 and 27 mL/kg) in
      anesthetized, paralyzed and mechanically ventilated male Wistar rats. Animals
      were randomized into two groups of 6 rats each: V (T)8 (V(T), 8 mL/kg; 61.50 +/-
      0.92 breaths/min; positive end-expiratory pressure, 3.0 cmH(2)O; peak airway
      pressure (PAW), 11.8 +/- 2.0 cmH(2)O), and V T27 (V(T), 27 mL/kg; 33.60 +/- 1.56
      breaths/min; positive end-expiratory pressure, none, and PAW, 22.7 +/- 4.0
      cmH(2)O). Throughout the experiment, mean PAW remained comparable between the two
      groups (6.33 +/- 0.21 vs 6.50 +/- 0.22 cmH(2)O). For rats in the V(T)27 group,
      inulin clearance (mL.min(-1).body weight(-1)) decreased acutely after 60 min of
      mechanical ventilation and even more significantly after 90 min, compared with
      baseline values (0.60 +/- 0.05 and 0.45 +/- 0.05 vs 0.95 +/- 0.07; P < 0.001),
      although there were no differences between groups in mean arterial pressure or
      gasometric variables. In the V(T)8 group, inulin clearance at 120 min of
      mechanical ventilation remained unchanged in relation to baseline values (0.72 +/
      0.03 vs 0.80 +/- 0.05). The V(T)8 and V(T)27 groups did not differ in terms of
      serum thiobarbituric acid reactive substances (3.97 +/- 0.27 vs 4.02 +/- 0.45
      nmol/mL) or endothelial nitric oxide synthase expression (94.25 +/- 2.75 vs 96.25
      +/- 2.39%). Our results show that glomerular filtration is acutely affected by
      high tidal volume ventilation but do not provide information about the mechanism.

PMID- 19855907
TI  - Comparison of I-FISH and G-banding for the detection of chromosomal abnormalities
      during the evolution of myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) patients with a normal karyotype constitute a
      heterogeneous group from a biological standpoint and their outcome is often
      unpredictable. Interphase fluorescence in situ hybridization (I-FISH) studies
      could increase the rate of detection of abnormalities, but previous reports in
      the literature have been contradictory. We performed I-FISH and conventional
      karyotyping (G-banding) on 50 MDS patients at diagnosis, after 6 and 12 months or
      at any time if a transformation to acute myeloid leukemia (AML) was detected.
      Applying a probe-panel targeting the centromere of chromosomes 7 and 8, 5q31,
      5p15.2 and 7q31, we observed one case with 5q deletion not identified by G
      banding. I-FISH at 6 and 12 months confirmed the karyotype results. Eight cases
      transformed to AML during follow-up, but no hidden clone was detected by I-FISH
      in any of them. The inclusion of I-FISH during follow-up of MDS resulted in a
      small improvement in abnormality detection when compared with conventional G
      banding.

PMID- 19855908
TI  - Effects of pneumonectomy on nitric oxide synthase expression and perivascular
      edema in the remaining lung of rats.
AB  - Pneumonectomy is associated with high mortality and high rates of complications.
      Postpneumonectomy pulmonary edema is one of the leading causes of mortality.
      Little is known about its etiologic factors and its association with the
      inflammatory process. The purpose of the present study was to evaluate the role
      of pneumonectomy as a cause of pulmonary edema and its association with gas
      exchange, inflammation, nitric oxide synthase (NOS) expression and
      vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included
      in the study. Eleven animals died during or after the procedure, 21 were
      submitted to left pneumonectomy and 10 to sham operation. These animals were
      sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in
      pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after
      pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical
      expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically
      significant difference in the expression of iNOS. The lumen-wall ratio and
      pO(2)/FiO(2) ratio did not differ between the operated and sham groups after
      pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no
      elevation of immunohistochemical expression of iNOS or neutrophil density,
      suggesting the absence of correlation with the inflammatory process or oxidative
      stress. The increased expression of eNOS may suggest an intrinsic production of
      NO without signs of vascular reactivity.

PMID- 19855909
TI  - Dialetics of balanced autonomy in disagreements between patients and oncological
      surgeons.
AB  - OBJECTIVE: To comprehend different logics of autonomy that are present in
      conflicts between surgical prescriptions and the expectations of patients with
      diagnoses of cancer. METHODOLOGICAL PROCEDURES: This is a qualitative study in
      which 11 semistructured interviews were conducted with oncological surgeons
      specializing in head and neck tumors, in the city of Rio de Janeiro, Southeastern
      Brazil, between 2000 and 2005. The participants were selected by means of chain
      sampling and the fieldwork was halted in accordance with the criterion of
      saturation. The discourse analysis technique was used to identify the premises
      that structured the concept of autonomy and would constitute the discursive
      dialectics within the context of patients who fight against undergoing surgery
      that is considered to be of mutilating nature. ANALYSIS OF RESULTS: At first, the
      surgeons expressed standardized statements centered on deontological concepts of
      autonomy. As they narrated their experiences, self-questioning that brought out
      contradictions regarding the routine concept of "informed resectability" was
      observed. At this point, the standardized discourse became permeated by self
      questioning about the need to return to the existential balance that had been
      harmed by the cancer. CONCLUSIONS: The narratives expressed demands for "balanced
      autonomy" in the form of a semi-project that is not aprioristically idealizable
      but is dependent on mutual interactions. The results indicated the need for
      reflection on the concept of autonomy as a linear, categorical and individual
      premise that, although superficially elaborated, governs everyday actions.

PMID- 19855910
TI  - Association between bullying at work and mental disorders: gender differences in
      the Italian people.
AB  - BACKGROUND: In the last few years the international literature has shown an
      increasing attention for the work as life-event stressor, for its organizational
      characteristics as well as for job insecurity and interpersonal conflicts.
      METHODS: We have studied 707 subjects who approached the Work Psychopathology
      Medical Centre of Naples to evaluate the DSM IV diagnoses and the degree of
      bullying at the workplace according to Leymann's definition. Two groups, with
      high and with low severity of bullying, were compared, mainly in relation to
      gender differences. RESULTS: The more frequent diagnoses were anxiety disorders
      (8.7% of the total), mood disorders (31.5%) and adjustment disorders (58.3%). The
      patients with higher degree of bullying were 55.7% among the subjects with
      anxiety disorders, 51.4% among the patients with adjustment disorders and 81.25%
      in the group with mood disorders. The odds of patients with severe bullying was
      1.602 times higher for males than for females. Independently by the gender, the
      odds of patients being in the group with severe bullying were more than three
      times higher for subjects with mood disorders than for patients suffering from
      anxiety and adjustment disorders. DISCUSSION: In the male gender, the psychiatric
      disturbances are more correlated to bullying at the workplace and this datum is
      especially linked to the gender differences found in the relationship between
      severity of bullying and adjustment disorders. Among female employees the
      psychopathological dimensions could be linked with a more multifactorial genesis
      in relation to their psychosocial role in the cultural context we examined
      (Southern Italy).

PMID- 19855912
TI  - Small bowel incarceration associated with posthysterectomy enterocele.
AB  - Enterocele represents a pelvic floor hernia with the sac most commonly protruding
      between the rectum and vagina. It may occur with or without prior hysterectomy
      and is very rarely complicated by small bowel obstruction. We report herein the
      case of a 70-year-old woman with a posthysterectomy enterocele presented with
      symptoms of small bowel obstruction and abdominal tenderness. The patient
      underwent exploratory laparotomy, which revealed small bowel incarceration. To
      our knowledge, this case represents the first published case of vaginal vault
      prolapse and enterocele associated with small bowel obstruction and
      incarceration. The pathogenesis, diagnosis, and treatment are discussed.

PMID- 19855911
TI  - Impact of psychiatric and social characteristics on HIV sexual risk behavior in
      Puerto Rican women with severe mental illness.
AB  - BACKGROUND: Latinos in the United States have been identified as a high-risk
      group for depression, anxiety, and substance abuse. HIV/AIDS has
      disproportionately impacted Latinos. Review findings suggest that HIV-risk
      behaviors among persons with severe mental illness (SMI) are influenced by a
      multitude of factors including psychiatric illness, cognitive-behavioral factors,
      substance use, childhood abuse, and social relationships. OBJECTIVE: To examine
      the impact of psychiatric and social correlates of HIV sexual risk behavior in
      Puerto Rican women with SMI. METHODS: Data collected longitudinally (from 2002 to
      2005) in semi-structured interviews and from non-continuous participant
      observation was analyzed using a cross-sectional design. Bivariate associations
      between predictor variables and sexual risk behaviors were examined using binary
      and ordinal logistic regression. Linear regression was used to examine the
      association between significant predictor variables and the total number of risk
      behaviors the women engaged in during the 6 months prior to baseline. RESULTS:
      Just over one-third (35.9%) of the study population (N = 53) was diagnosed with
      bipolar disorder and GAF scores ranged from 30 to 80 with a median score of 60.
      Participants ranged in age from 18 to 50 years (M = 32.6 +/- 8.7), three-fourths
      reported a history of either sexual or physical abuse or of both in childhood,
      and one-fourth had abused substances in their lifetimes. Bivariate analyses
      indicated that psychiatric and social factors were differentially associated with
      sexual risk behaviors. Multivariate linear regression models showed that
      suffering from increased severity of psychiatric symptoms and factors and living
      below the poverty line are predictive of engagement in a greater number of HIV
      sexual risk behaviors. PRACTICAL IMPLICATIONS: Puerto Rican women with SMI are at
      high risk for HIV infection and are in need of targeted sexual risk reduction
      interventions that simultaneously address substance abuse prevention and
      treatment, childhood abuse, and the indirect effects associated with SMI such as
      living in poverty. Mental health programs should address risk behavior among
      adults with SMI in the context of specific symptomatology and comorbidities.

PMID- 19855913
TI  - A 31-year-old woman with urethral duplication, stress urinary incontinence,
      uterovaginal prolapse, and rectal prolapse.
AB  - Urethral duplication is a rare finding in females, with fewer than 40 cases
      published since 1970. We report a case of urethral duplication in a woman with
      uterovaginal and rectal prolapse but without other associated congenital
      anomalies. On urodynamic and cystoscopic evaluation, an accessory urethra was
      noted to emerge from beneath the clitoral hood. The patient underwent exploratory
      laparotomy and transabdominal excision of the rudimentary urethral orifice with
      concurrent transvaginal prolapse repair and rectopexy. At 5-year follow-up, the
      patient continued to be continent and without prolapse.

PMID- 19855914
TI  - Risk factors of treatment failure of midurethral sling procedures for women with
      urinary stress incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Midurethral sling (MUS) is now the first line
      surgical treatment for female stress urinary incontinence. Our aim was to
      identify predictors for MUS failure. METHODS: A total of 1,225 consecutive women
      with urodynamic urinary stress incontinence had a synthetic MUS (955 retropubic
      and 270 transobturator) at our institution between 1999 and 2007. Multivariate
      analysis was performed in order to identify independent risk factors for failure.
      RESULTS AND CONCLUSIONS: At a mean follow-up of 50 +/- 24 months (range, 12-114),
      the subjective cure rate was 84.7%. Multivariate analysis revealed that BMI >25
      (OR, 2.9), mixed incontinence (OR, 2.4), previous continence surgery (OR, 2.2),
      intrinsic sphincter deficiency (OR, 1.9), and diabetes mellitus (OR, 1.8) are
      significant independent predictors for MUS failure. Concomitant prolapse surgery
      decreased the likelihood of surgical failure after MUS (OR, 0.6). Patient's age
      and the type of the sling were not found to be risk factors for surgical failure.

PMID- 19855915
TI  - A preliminary assessment of polycyclic aromatic hydrocarbon distribution in the
      kenting coral reef waters of southern Taiwan.
AB  - This distribution and variation of 45 polycyclic aromatic hydrocarbons (PAHs) in
      the waters of Kenting coral reefs were investigated by using sensitive research
      grade sampling and analytical methods. The concentration levels of total PAHs
      (including particulate and dissolved PAHs) in the Kenting waters were relatively
      low, ranging from 2.2 to 34.4 ng/L. There was no significant spatial difference
      in PAH concentrations among the sampling stations, even between the surface and
      bottom waters. The fraction of dissolved PAHs on average was greater than that of
      particulate PAHs due to the small amount of total suspended particles. The
      partition coefficients between the particulate and dissolved phase (log K(oc))
      were positively correlated with their log K(ow) values (r(2) = 0.67, n = 80),
      except for the more hydrophobic PAHs with log K(ow) values greater than 5.91.
      Results of principal component analysis indicate that the patterns of particulate
      PAH compositions were similar through the Kenting waters in the fall and winter,
      whereas there was a significant spatial difference between the spring and summer
      samples, which might be affected by a combination of land runoff and coastal
      currents. PAHs along the Kenting coasts were dominated by low-molecular PAHs,
      which have higher solubility than high-molecular PAHs. Based on isomer ratios,
      analysis of the source of PAHs in the Kenting coastal waters demonstrated that
      the PAHs come mostly from petroleum and, to a lesser degree, from combustion.

PMID- 19855916
TI  - Permeation of herbicidal dichlobenil from a Casoron formulation through nitrile
      gloves.
AB  - The aim of this study was to measure permeation of the herbicide dichlobenil in
      Casoron 4G through disposable and chemically protective nitrile gloves using an
      American Society for Testing and Materials-type permeation cell and a closed-loop
      system employing two different solvents (hexane and water) and two different
      challenge situations (aqueous emulsion and solid formulation). Capillary gas
      chromatography-mass spectrometry was used for quantification purposes. The
      chemically protective glove did not allow any permeation up to 8 h for the solid
      formulation and water-collection challenges, but permeation was detected in all
      other challenges. The disposable glove allowed the most permeation, and the solid
      formulation challenge with water collection necessitated that a dichlobenil
      equivalent be calculated because of the presence of its hydrolysis degradation
      product 2,6-dichlorobenzamide. Permeation from the solid formulation was
      detectable by hexane collection for both the disposable and chemically protective
      gloves and by water collection for the disposable glove. It was concluded that
      hexane-solvent collection was not valid for the disposable glove at 4 and 8 h of
      permeation in the solid Casoron challenge or for the aqueous emulsion challenge
      at 8 h relative to the water-collection solvent data. The hexane-solvent
      collection for the chemically protective glove was valid for the 8-h solid
      formulation challenge but not for the 8-h aqueous-solution challenge. All water
      solvent collections were valid; however, dichlobenil usually permeated the
      gloves.

PMID- 19855917
TI  - Endoscopic removal of a suprasellar arachnoid cyst: an anatomical study with
      special reference to skull base.
AB  - BACKGROUND: Suprasellar arachnoid cysts are rare entities in adults, representing
      10% of all cysts. Endoscopic treatment is now preferred for this pathology,
      allowing a new anatomical approach to skull base structures. OBJECTIVES: The aim
      of this study is to present the relevant anatomy of the skull base viewed during
      an endoscopic procedure for a suprasellar arachnoid cyst. METHOD: A 77-year-old
      man with 6 months history of walking disorder was referred for neurosurgical
      evaluation. Physical examination did not show any oculomotor or endocrine
      disorder. Sagittal T1-weighted MRI demonstrated a large suprasellar arachnoid
      cyst. The patient underwent a ventriculocystocisternostomy without complications.
      Postoperative neurologic examination showed an initial improvement of walking
      disorders. Cerebral CT scan showed a slight reduction in cyst dimensions.
      RESULTS: During the endoscopic procedure, the anatomical view of the skull base
      was demonstrative. From the interior of the cyst we were able to identify the
      following structures: the clivus, pituitary stalk, pituitary gland, basilar
      artery, posterior cerebral arteries, posterior communicating arteries, oculomotor
      nerves and the superior wall of cavernous sinus. We identified a slit valve
      mechanism in the arachnoid next to the basilar artery. CONCLUSION:
      Ventriculocystocisternostomy is a useful procedure in treating arachnoid cyst.
      Moreover, during this procedure, the endoscope allows for better and safer
      visualization of skull base structures.

PMID- 19855919
TI  - Clinical characteristics of patients with type 2 diabetes mellitus at the time of
      insulin initiation: INSTIGATE observational study in Spain.
AB  - Little information is available on the management of patients with type 2
      diabetes mellitus (DM2) in regular clinical practice, prior to and at the point
      of initiating treatment with insulin. The INSTIGATE study provides a description
      of the clinical profile of the patient with DM2 who begins treatment with insulin
      in both primary and secondary care. A total of 224 patients who had been
      diagnosed with DM2, were not responding to oral treatment, and began receiving
      insulin were included in the INSTIGATE study in Spain. Demographic data were
      collected, as well as data on macro- and microvascular complications of diabetes
      and comorbidities, past medical history of diabetes and oral treatment
      administered, the clinical severity of diabetes (HbA1c concentration) and insulin
      treatment initiated. Mean age of the sample was 65.4 years and 56.7% were men.
      There were 87% of patients who had a diagnosis of at least one significant
      comorbidity, notably hypertension and hyperlipidemia. The patient profile for
      metabolic syndrome was met by 75.1% of the patients. There was a higher incidence
      of macrovascular complications (38.4%) than microvascular complications (16.1%).
      Prior to insulin initiation, the most recent mean HbA1c was 9.2%. The majority of
      patients had been treated in the last 12 months with sulfonylureas and/or
      metformin (69.6 and 57.6%). The most common treatment prior to insulinization was
      the co-administration of two oral antidiabetics (OADs) (37.5%). Patients with DM2
      observed in the study presented with elevated mean HbA1c and body mass index
      levels, comorbidities and complications related to diabetes at the time of
      insulin initiation. Changes and adjustments in treatment from diagnosis of
      diabetes occur when HbA1c levels are far above those recommended by the IDF
      (International Diabetes Federation), a factor which could be contributing to the
      development of both macrovascular and microvascular complications in the patient
      profile described in the study.

PMID- 19855918
TI  - Variation in the checkpoint kinase 2 gene is associated with type 2 diabetes in
      multiple populations.
AB  - Identification and characterization of the genetic variants underlying type 2
      diabetes susceptibility can provide important understanding of the etiology and
      pathogenesis of type 2 diabetes. We previously identified strong evidence of
      linkage for type 2 diabetes on chromosome 22 among 3,383 Hypertension Genetic
      Epidemiology Network (HyperGEN) participants from 1,124 families. The checkpoint
      2 (CHEK2) gene, an important mediator of cellular responses to DNA damage, is
      located 0.22 Mb from this linkage peak. In this study, we tested the hypothesis
      that the CHEK2 gene contains one or more polymorphic variants that are associated
      with type 2 diabetes in HyperGEN individuals. In addition, we replicated our
      findings in two other Family Blood Pressure Program (FBPP) populations and in the
      population-based Atherosclerosis Risk in Communities (ARIC) study. We genotyped
      1,584 African-American and 1,531 white HyperGEN participants, 1,843 African
      American and 1,569 white GENOA participants, 871 African-American and 1,009 white
      GenNet participants, and 4,266 African-American and 11,478 white ARIC
      participants for four single nucleotide polymorphisms (SNPs) in CHEK2. Using
      additive models, we evaluated the association of CHEK2 SNPs with type 2 diabetes
      in participants within each study population stratified by race, and in a meta
      analysis, adjusting for age, age(2), sex, sex-by-age interaction, study center,
      and relatedness. One CHEK2 variant, rs4035540, was associated with an increased
      risk of type 2 diabetes in HyperGEN participants, two replication samples, and in
      the meta-analysis. These results may suggest a new pathway in the pathogenesis of
      type 2 diabetes that involves pancreatic beta-cell damage and apoptosis.

PMID- 19855920
TI  - Diabetes and the risk of sudden cardiac death, the Atherosclerosis Risk in
      Communities study.
AB  - Studies suggest that diabetes may specifically elevate the risk of sudden cardiac
      death in excess of other heart disease outcomes. In this study, we examined the
      association of type 2 diabetes with the incidence of sudden cardiac death when
      compared to the incidence of non-sudden cardiac death and non-fatal myocardial
      infarction (MI). We used data from the Atherosclerosis Risk in Communities (ARIC)
      study to examine the incidence of sudden and non-sudden cardiac death and non
      fatal MI among persons with and without diabetes in follow-up from the baseline
      data collection (1987-1989) through December 31, 2001. There were 209 cases of
      sudden cardiac death, 119 of non-sudden cardiac death, and 739 of non-fatal MI
      identified in this cohort over an average 12.4 years of follow-up. In analyses
      adjusted for age, race/ARIC center, gender, and smoking, the Cox proportional
      hazard ratio of the association of baseline diabetes was 3.77 (95% CI 2.82, 5.05)
      for sudden cardiac death, 3.78 (95% CI 2.57, 5.53) for non-sudden cardiac death,
      and 3.20 (95% CI 2.71, 3.78) for non-fatal MI. Elevated risk for each of the
      three outcomes associated with diabetes was independent of adjustment for
      measures of blood pressure, lipids, inflammation, hemostasis, and renal function.
      Among those with diabetes, the risk of cardiac death, but not of non-fatal MI,
      was similar for men and women. Findings from this prospective, population-based
      cohort investigation indicate that diabetes does not confer a specific excess
      risk of sudden cardiac death. Our results suggest that diabetes attenuates gender
      differences in the risk of fatal cardiac events.

PMID- 19855921
TI  - The effects of telmisartan on mechanical responses of left ventricular papillary
      muscle in rats with streptozotocin-induced diabetes mellitus.
AB  - The purpose of this study was to investigate the effects of telmisartan (5 * 10(
      5) M) on the mechanical response of left ventricular papillary muscle in rats
      with streptozotocin-induced diabetes mellitus. We studied 32 rats; 16 were
      rendered diabetic by a single intravenous injection of streptozotocin (45 mg kg(
      1) i.v.) and 16 formed a non-diabetic control group. Diabetic animals were
      divided into two groups: diabetic-telmisartan group and the diabetic-control
      group. Non-diabetic controls were further divided into the non-diabetic
      telmisartan group and the non-diabetic-control group. We found: (1) Muscle twitch
      tension (P (0)) and contraction and relaxation rates were significantly lower in
      diabetic controls than in the other groups. (2) Telmisartan significantly
      increased P (0) in both diabetic and non-diabetic rats. (3) Times to peak tension
      and half-relaxation were significantly greater in groups DC and DT than in the
      non-diabetics. In conclusion, our data suggest that telmisartan attenuates
      diabetes-induced impairment of diabetic rat papillary muscles, and may thus be
      able to reduce cardiac complications in diabetes.

PMID- 19855922
TI  - Body mass index and acid phosphatase locus 1 in diabetic disorders.
AB  - The polymorphic enzyme acid phosphatase locus 1 (ACP1) is a candidate gene for
      obesity disorders. The enzyme is able to dephosphorylate the insulin receptor.
      Our group has observed a lower plasma glucose level in diabetic subjects carrying
      the low activity ACP1 phenotypes A and BA, and a positive association between
      these genotypes and body mass index (BMI). We have now analysed the relationship
      between BMI and ACP1 in gestational diabetes and in women with type 1 diabetes.
      We have studied 106 Caucasian women with type 1 diabetes who had previously
      delivered a liveborn infant, 99 Caucasian women who had had gestational diabetes
      and 387 healthy fertile women from the same population as controls. ACP1
      phenotype was determined by starch gel electrophoresis. In overweight women (BMI
      > 25), the proportion of low activity ACP1 phenotypes is much lower in type 1
      diabetes than in gestational diabetes and in healthy females. In women with BMI
      <= 25, the proportion of low activity ACP1 phenotypes is slightly lower in
      gestational diabetes than in type 1 diabetes. Low activity ACP1 phenotypes have
      diverse effects on susceptibility to overweight depending on the class of
      diabetic disorder: in subjects with type 2 diabetes and in subjects with
      gestational diabetes low activity ACP1 phenotypes predispose to an increase in
      BMI, while in type 1 diabetes these ACP1 phenotypes seem to protect from
      overweight.

PMID- 19855923
TI  - Alanine-aminotransferase levels predict impaired glucose tolerance in a worksite
      population.
AB  - Insulin resistance and impaired glucose tolerance precede the development of type
      2 diabetes. In 2006, the BASF Occupational Medicine and Health Protection
      Department offered a diabetes screening program for 33,000 employees. 1,594
      employees had their diabetes risk tested: 285 employees were at medium to high
      risk for diabetes type 2, according to the Finrisk score. Hundred and fifty-seven
      of these individuals underwent oral glucose tolerance testing: 22 were shown to
      have impaired glucose tolerance (IGT), and 5 had manifest diabetes. Thus, 18% of
      this worksite sample population were affected by IGT or type 2 diabetes. A total
      of 87% were affected by metabolic syndrome (MS) according to the International
      Diabetes Federation (IDF) criteria. At baseline, individuals with normal glucose
      tolerance and impaired glucose tolerance differed significantly with respect to
      fasting glucose (97 +/- 8 vs. 103 +/- 10 mg/dl, P < 0.01), HbA1c (5.5 +/- 0.3 vs.
      5.7 +/- 0.4%, P < 0.01), and alanine-aminotransferase (ALT) (28 +/- 15 vs. 36 +/-
      18 U/I, P < 0.05). In binary logistic regression analysis adjusted for age and
      gender, fasting glucose and ALT were the only independent predictors of impaired
      glucose tolerance (OR 4.8 [1.24-24.8] and OR 5.5 [1.2-24.8]), while age and HbA1c
      had only borderline significance (OR 3.9 [0.94-15.92] and OR 2.8 [0.94-8.67]).
      Waist circumference, BMI, triglycerides, and HDL as central components of the MS
      had no predictive value for impaired glucose tolerance. In summary, in this
      particular sample population, fasting glucose and ALT were the only significant
      predictors of IGT. These data point to an important role of the liver in insulin
      resistance and the development of impaired glucose tolerance in the relatively
      young and small population studied.

PMID- 19855924
TI  - Acute subdural hematoma from ruptured cerebral aneurysm.
AB  - PURPOSE: The combination of ruptured aneurysms with acute subdural hematomas
      (aSDHs) is a rare presentation. Patients with aSDH associated with aneurysmal
      bleeding represent a subgroup within the spectrum of aneurysmatic hemorrhage. We
      summarize the clinical characteristics, diagnostic evaluation, and management of
      a series of cases presenting with aSDH associated with aneurysmal subarachnoid
      hemorrhage (SAH). METHODS: Medical records and surgical reports of 743
      consecutive patients admitted to our institution with SAH from January 1995 to
      December 2007 were screened to detect cases of associated aSDH. Admission
      evaluations included the Glasgow Coma Scale (GCS) and the subarachnoid grade of
      the World Federation of Neurosurgical Societies (WFNS). Radiological assessment
      included computer tomography (CT) scan, CT angiography (CTA), and digital
      subtraction angiography (DSA). The presence and volume of SAH, intracerebral
      hemorrhage (ICH), and aSDH were documented. Outcome was measured in terms of
      Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) at 4-8 months.
      RESULTS: A total of seven cases (0.9%) presenting with aSDH (mean width: 11.2 mm
      +/- 4.8 mm, range: 5-20 mm) attributable to SAH were documented. Three of these
      patients were admitted with a suspicion of trauma. Five patients presented with
      WFNS grade 5, one patient with WFNS grade 3, and one patient with WFNS grade 1.
      All patients underwent evacuation of the aSDH. In four patients, surgical
      obliteration of the aneurysm was achieved in the same procedure. Two patients
      underwent delayed occlusion of the aneurysm: one by coiling and one by clipping.
      Three of the seven patients recovered completely from their neurological deficits
      (GOS 5, mRS 0-1), three recovered with mild disability (GOS 4, mRS 2-3), and one
      died within 8 h after the decompressive procedure. CONCLUSIONS: The incidence of
      aSDH associated with SAH is low. Most of the patients with aSDH due to a ruptured
      aneurysm present in exceptionally poor neurological condition. Nevertheless,
      rapid surgical treatment of the hematoma and aneurysm obliteration can lead to a
      favorable outcome. Routine CTA should be performed in all patients presenting
      with an aSDH associated with SAH and no clear history of trauma.

PMID- 19855925
TI  - Structural analysis of the complex between calmodulin and full-length myelin
      basic protein, an intrinsically disordered molecule.
AB  - Myelin basic protein (MBP) is present between the cytoplasmic leaflets of the
      compact myelin membrane in both the peripheral and central nervous systems, and
      characterized to be intrinsically disordered in solution. One of the best
      characterized protein ligands for MBP is calmodulin (CaM), a highly acidic
      calcium sensor. We pulled down MBP from human brain white matter as the major
      calcium-dependent CaM-binding protein. We then used full-length brain MBP, and a
      peptide from rodent MBP, to structurally characterize the MBP-CaM complex in
      solution by small-angle X-ray scattering, NMR spectroscopy, synchrotron radiation
      circular dichroism spectroscopy, and size exclusion chromatography. We determined
      3D structures for the full-length protein-protein complex at different
      stoichiometries and detect ligand-induced folding of MBP. We also obtained
      thermodynamic data for the two CaM-binding sites of MBP, indicating that CaM does
      not collapse upon binding to MBP, and show that CaM and MBP colocalize in myelin
      sheaths. In addition, we analyzed the post-translational modifications of rat
      brain MBP, identifying a novel MBP modification, glucosylation. Our results
      provide a detailed picture of the MBP-CaM interaction, including a 3D model of
      the complex between full-length proteins.

PMID- 19855926
TI  - Infusion of ibandronate once every 3 months effectively decreases bone resorption
      markers and increases bone mineral density in Chinese postmenopausal osteoporotic
      women: a 1-year study.
AB  - The efficacy and safety of intravenous ibandronate were evaluated in
      postmenopausal osteoporosis women in China. In this multicenter, positive drug
      controlled study, 158 postmenopausal osteoporotic women were randomized to
      receive 2 mg ibandronate given intravenously once every 3 months or 70 mg
      alendronate given orally once per week. All women also received supplemental
      calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients
      completed the 1-year study. Ibandronate produced mean increases in bone mineral
      density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03%
      at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at
      the femoral neck, and 2.99% at the trochanter were observed in the alendronate
      group. No significant difference was found between the two groups in BMD in all
      sites measured. Significant decreases in serum c-telopeptide of type I collagen
      (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3
      months of treatment, respectively; these serum CTX and ALP levels were then
      maintained at the decreased levels throughout the study period (12 months). No
      changes of stature were found in the patients of the two groups. Adverse events
      were similar in the two groups, except more mild muscle pain was observed in the
      first month after infusion of ibandronate than with oral alendronate (P < 0.001).
      The results observed in Chinese patients may support the observation that
      intravenous ibandronate significantly reduced bone resorption and increased BMD
      with good tolerance in Chinese postmenopausal osteoporotic women. Use of
      intravenous ibandronate possibly could potentially improve compliance as compared
      with other oral bisphosphonates because it may avoid the peptic side effects of
      oral bisphosphonate.

PMID- 19855927
TI  - Correlation of left ventricular dyssynchrony with myocardial stunning using dual
      single photon emission computed tomography of (123)iodine-beta-methyl iodophenyl
      pentadecanoic acid and (201)thallium scintigraphy after reperfusion therapy.
AB  - OBJECTIVE: Left ventricular (LV) dyssynchrony after reperfusion therapy has been
      closely examined as a cause of chronic remodeling, but the details have not been
      clarified. The present study measured LV dyssynchrony appearing immediately after
      reperfusion therapy using real-time three-dimensional echocardiography (RT-3DE),
      and assessed the significance of this phenomenon in relation to dual single
      photon emission computed tomography (SPECT) of (123)iodine beta methyliodophenyl
      pentadecanoic acid ((123)I-BMIPP) and (201)thallium ((201)Tl). METHODS: Subjects
      comprised 58 patients with first-time acute myocardial infarction who received
      reperfusion therapy and underwent RT-3DE and dual SPECT of (123)I-BMIPP and
      (201)Tl within two weeks of onset. Two dyssynchrony parameters were measured
      using RT-3DE in the acute phase and six months later. After evaluating the
      correlation of these dyssynchrony parameters to resting (201)Tl uptake, (201)Tl
      washout, (123)I-BMIPP uptake, and (201)Tl-(123)I-BMIPP discrepancy (Tl-BMIPP
      discrepancy), we compared scintigraphic parameters in the chronic phase between
      groups with improved dyssynchrony and those without. RESULTS: Acute dyssynchrony
      exhibited a significant positive correlation to Tl-BMIPP discrepancy and it was
      significantly increased in the group with improved dyssynchrony in the chronic
      phase, revealing close relationship between dyssynchrony and Tl-BMIPP
      discrepancy. Then the subjects were divided into positive Tl-BMIPP discrepancy
      and negative discrepancy groups, and the parameters of cardiac function were
      compared between them. In the chronic phase, improved cardiac function was
      observed in the group with positive Tl-BMIPP discrepancy compared to negative
      discrepancy. CONCLUSION: LV dyssynchrony after reperfusion therapy correlates
      positively with Tl-BMIPP discrepancy, reflecting acute myocardial stunning, in
      which ventricular contraction improves during the chronic phase.

PMID- 19855929
TI  - Editorial: proceedings of The Second International Conference of the French
      speaking Society for Theoretical Biology.

PMID- 19855928
TI  - Activated EGFR signaling increases proliferation, survival, and migration and
      blocks neuronal differentiation in post-natal neural stem cells.
AB  - Recent evidence supports the notion that transformation of undifferentiated
      neural stem cell (NSC) precursors may contribute to the development of
      glioblastoma multiforme (GBM). The over-expression and mutation of the epidermal
      growth factor receptor (EGFR), along with other cellular pathway mutations, plays
      a significant role in GBM maintenance progression. Though EGFR signaling is
      important in determining neural cell fate and conferring astrocyte
      differentiation, there is a limited understanding of its role in NSC and tumor
      stem cell (TSC) biology. We hypothesized that EGFR expression and mutation in
      post-natal NSCs may contribute to cellular aggressiveness including enhanced
      cellular proliferation, survival and migration. Stable subclones of C17.2 murine
      NSCs were transfected to over-express either the wild-type EGFR (wtEGFR) or its
      most common mutated variant EGFRvIII. Activated EGFR signaling in these cells
      induced behaviors characteristic of GBM TSCs, including enhanced proliferation,
      survival and migration, even in the absence of EGF ligand. wtEGFR activation was
      also found to block neuronal differentiation and was associated with a dramatic
      increase in chemotaxis in the presence of EGF. EGFRvIII expression lead to an
      increase in NSC proliferation and survival, while it simultaneously blocked
      neuronal differentiation and promoted glial fate. Our findings suggest that
      activated EGFR signaling enhances the aggressiveness of NSCs. Understanding the
      regulatory mechanisms of NSCs may lend insight into deregulated mechanisms of GBM
      TSC invasion, proliferation, survival and resistance to current treatment
      modalities.

PMID- 19855930
TI  - Ins and outs of systems biology vis-a-vis molecular biology: continuation or
      clear cut?
AB  - The comprehension of living organisms in all their complexity poses a major
      challenge to the biological sciences. Recently, systems biology has been proposed
      as a new candidate in the development of such a comprehension. The main objective
      of this paper is to address what systems biology is and how it is practised. To
      this end, the basic tools of a systems biological approach are explored and
      illustrated. In addition, it is questioned whether systems biology
      'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The
      strength of this claim appears to depend on how molecular and systems biology are
      characterised and on how reductionism is interpreted. Doing credit to molecular
      biology and to methodological reductionism, it is argued that the distinction
      between molecular and systems biology is gradual rather than sharp. As such, the
      classical challenge in biology to manage, interpret and integrate biological data
      into functional wholes is further intensified by systems biology's use of
      modelling and bioinformatics, and by its scale enlargement.

PMID- 19855931
TI  - A novel antifungal analog peptide derived from protaetiamycine.
AB  - Previously, the 9-mer analog peptides, 9Pbw2 and 9Pbw4, were designed based on a
      defensin-like peptide, protaetiamycine isolated from Protaetia brevitarsis. In
      this study, antifungal effects of the analog peptides were investigated. The
      antifungal susceptibility testing exhibited that 9Pbw4 contained more potent
      antifungal activities than 9Pbw2. A PI influx assay confirmed the effects of the
      analog peptides and demonstrated that the peptides exerted their activity by a
      membrane-active mechanism, in an energy-independent manner. As the noteworthy
      potency of 9Pbw4, the mechanism(s) of 9Pbw4 were further investigated. The
      membrane studies, using rhodamine-labeled giant unilamellar vesicle (GUV) and
      fluorescein isothiocyanate (FITC)-dextran loaded liposome, suggested that the
      membrane-active mechanism of 9Pbw4 could have originated from the poreforming
      action and the radii of pores was presumed to be anywhere from 1.8 nm to 3.3 nm.
      These results were confirmed by 3D-flow cytometric contour-plot analysis. The
      present study suggests a potential of 9Pbw4 as a novel antifungal peptide.

PMID- 19855933
TI  - Development of inhibitors against TraR quorum-sensing system in Agrobacterium
      tumefaciens by molecular modeling of the ligand-receptor interaction.
AB  - The quorum sensing (QS) inhibitors that antagonize TraR, a receptor protein for N
      3-oxo-octanoyl-L-homoserine lactones (3-oxo-C8-HSL), a QS signal of Agrobacterium
      tumefaciens were developed. The structural analogues of 3-oxo-C8-HSL were
      designed by in silico molecular modeling using SYBYL packages, and synthesized by
      the solid phase organic synthesis (SPOS) method, where the carboxamide bond of 3
      oxo-C8-HSL was replaced with a nicotinamide or a sulfonamide bond to make
      derivatives of N-nicotinyl-L-homoserine lactones or N-sulfonyl-L-homoserine
      lactones. The in vivo inhibitory activities of these compounds against QS
      signaling were assayed using reporter systems and compared with the estimated
      binding energies from the modeling study. This comparison showed fairly good
      correlation, suggesting that the in silico interpretation of ligand-receptor
      structures can be a valuable tool for the pre-design of better competitive
      inhibitors. In addition, these inhibitors also showed anti-biofilm activities
      against Pseudomonas aeruginosa.

PMID- 19855932
TI  - Identification and characterization of a putative basic helix-loop-helix (bHLH)
      transcription factor interacting with calcineurin in C. elegans.
AB  - Calcineurin is a Ca(2+)/Calmodulin activated Ser/Thr phosphatase that is well
      conserved from yeast to human. It is composed of catalytic subunit A (CnA) and
      regulatory subunit B (CnB). C. elegans homolog of CnA and CnB has been annotated
      to tax-6 and cnb-1, respectively and in vivo function of both genes has been
      intensively studied. In C. elegans, calcineurin play roles in various signaling
      pathways such as fertility, movement, body size regulation and serotonin-mediated
      egg laying. In order to understand additional signaling pathway(s) in which
      calcineurin functions, we screened for binding proteins of TAX-6 and found a
      novel binding protein, HLH-11. The HLH-11, a member of basic helix-loop-helix
      (bHLH) proteins, is a putative counterpart of human AP4 transcription factor.
      Previously bHLH transcription factors have been implicated to regulate many
      developmental processes such as cell proliferation and differentiation, sex
      determination and myogenesis. However, the in vivo function of hlh-11 is largely
      unknown. Here, we show that hlh-11 is expressed in pharynx, intestine, nerve
      cords, anal depressor and vuvla muscles where calcineurin is also expressed.
      Mutant analyses reveal that hlh-11 may have role(s) in regulating body size and
      reproduction. More interestingly, genetic epistasis suggests that hlh-11 may
      function to regulate serotonin-mediated egg laying at the downstream of tax-6.

PMID- 19855934
TI  - Insulin-like growth factor-I-induced androgen receptor activation is mediated by
      the PI3K/Akt pathway in C2C12 skeletal muscle cells.
AB  - Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well
      known effectors of skeletal muscle, the molecular mechanism by which signaling
      pathways integrating AR and IGF-I in skeletal muscle cells has not been
      previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene
      expression and activation of AR in skeletal muscle cells was investigated. C2C12
      cells were treated with IGF-I in the absence or presence of inhibitors of
      PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway
      with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR
      phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR
      mRNA and skeletal alpha-actin mRNA were blocked by LY294002 or Wortmannin.
      Confocal images showed that IGF-I-induced AR translocation from cytosol to
      nucleus was inhibited significantly in response to treatment with LY294002 or
      Wortmannin. The present results suggest that modulating effect of IGF-I on AR
      gene expression and activation in C2C12 mouse skeletal muscle cells is mediated
      at least in part by the PI3K/Akt pathway.

PMID- 19855935
TI  - The p53-p21(Cip1/WAF1) pathway is necessary for cellular senescence induced by
      the inhibition of protein kinase CKII in human colon cancer cells.
AB  - We have previously shown that the down-regulation of protein kinase CKII activity
      is tightly associated with cellular senescence of human fibroblast IMR-90 cells.
      Here, we examined the roles of p53 and p21(Cip1/WAF1) in senescence development
      induced by CKII inhibition using wild-type, isogenic p53-/- and isogenic p21-/-
      HCT116 human colon cancer cell lines. A senescent marker appeared after staining
      for senescence-associated beta-galactosidase activity in wild-type HCT116 cells
      treated with CKII inhibitor or CKIIalpha siRNA, but this response was almost
      abolished in p53- or p21(Cip1/WAF1)-null cells. Increased cellular levels of p53
      and p21(Cip1/WAF1) protein occurred with the inhibition of CKII. CKII inhibition
      upregulated p53 and p21(Cip1/WAF1) expression at post-transcriptional level and
      transcription level, respectively. RB phosphorylation significantly decreased in
      cells treated with CKII inhibitor. Taken together, this study shows that the
      activation of the p53-p21(Cip1/WAF1) pathway acts as a major mediator of cellular
      senescence induced by CKII inhibition.

PMID- 19855936
TI  - ADAM7 is associated with epididymosomes and integrated into sperm plasma
      membrane.
AB  - During epididymal transit, mammalian sperm acquire selected proteins secreted by
      the epididymis. We previously showed that a disintegrin and metalloprotease
      (ADAM) 7 is expressed specifically in the epididymis and transferred to the sperm
      surface during epididymal transit. Here, we show that mouse ADAM7 secreted to the
      epididymal lumen is associated with membranous vesicles known as epididymosomes.
      Furthermore, we found that ADAM7 can be transferred directly from epididymal
      vesicles to sperm and that it is an integral plasma membrane protein in sperm.
      Thus, our study provides new information regarding the unique mode of secretion
      and interaction of ADAM7 during the epididymis-to-sperm transfer process.

PMID- 19855937
TI  - The robust phylogeny of Korean wild boar (Sus scrofa coreanus) using partial D
      loop sequence of mtDNA.
AB  - In order to elucidate the precise phylogenetic relationships of Korean wild boar
      (Sus scrofa coreanus), a partial mtDNA D-loop region (1,274 bp, NC_000845
      nucleotide positions 16576-1236) was sequenced among 56 Korean wild boars. In
      total, 25 haplotypes were identified and classified into four distinct subgroups
      (K1 to K4) based on Bayesian phylogenetic analysis using Markov chain Monte Carlo
      methods. An extended analysis, adding 139 wild boars sampled worldwide, confirmed
      that Korean wild boars clearly belong to the Asian wild boar cluster.
      Unexpectedly, the Myanmarese/Thai wild boar population was detected on the same
      branch as Korean wild boar subgroups K3 and K4. A parsimonious median-joining
      network analysis including all Asian wild boar haplotypes again revealed four
      maternal lineages of Korean wild boars, which corresponded to the four Korean
      wild boar subgroups identified previously. In an additional analysis, we
      supplemented the Asian wild boar network with 34 Korean and Chinese domestic pig
      haplotypes. We found only one haplotype, C31, that was shared by Chinese wild,
      Chinese domestic and Korean domestic pigs. In contrast to our expectation that
      Korean wild boars contributed to the gene pool of Korean native pigs, these data
      clearly suggest that Korean native pigs would be introduced from China after
      domestication from Chinese wild boars.

PMID- 19855938
TI  - Structure and expression of OsUBP6, an ubiquitin-specific protease 6 homolog in
      rice (Oryza sativa L.).
AB  - Although the possible cellular roles of several ubiquitin-specific proteases
      (UBPs) were identified in Arabidopsis, almost nothing is known about UBP homologs
      in rice, a monocot model plant. In this report, we searched the rice genome
      database ( http://signal.salk.edu/cgi-bin/RiceGE ) and identified 21 putative UBP
      family members (OsUBPs) in the rice genome. These OsUBP genes each contain a
      ubiquitin carboxyl-terminal hydrolase (UCH) domain with highly conserved Cys and
      His boxes and were subdivided into 9 groups based on their sequence identities
      and domain structures. RT-PCR analysis indicated that rice OsUBP genes are
      expressed at varying degrees in different rice tissues. We isolated a full-length
      cDNA clone for OsUBP6, which possesses not only a UCH domain, but also an N
      terminal ubiquitin motif. Bacterially expressed OsUBP6 was capable of dismantling
      K48-linked tetraubiquitin chains in vitro. Quantitative real-time RT-PCR
      indicated that OsUBP6 is constitutively expressed in different tissues of rice
      plants. An in vivo targeting experiment showed that OsUBP6 is predominantly
      localized to the nucleus in onion epidermal cells. We also examined how knock-out
      of OsUBP6 affects developmental growth of rice plants. Although homozygous T3
      osubp6 T-DNA insertion mutant seedlings displayed slower growth relative to wild
      type seedlings, mature mutant plants appeared to be normal. These results raise
      the possibility that loss of OsUBP6 is functionally compensated for by an as-yet
      unknown OsUBP homolog during later stages of development in rice plants.

PMID- 19855939
TI  - Rhythmic expression of mitogen activated protein kinase activity in rice.
AB  - Mitogen activated protein kinase (MAPK) are known to get activated during various
      stress signals and transduce the message from the cell membrane to the nucleus
      for appropriate cellular reorganization. Though, a certain basal activity of MAPK
      is often observed in the control plants. Prolonged exposure of rice plants to
      lowered or elevated temperature exhibited a rhythm in the activation of MAPKs. We
      analyzed existence of a possible endogenous rhythm in the activity of MAPKs in
      rice plants. The plants growing at constant temperature entrained in 16/8 h day
      night cycle showed diurnal rhythm in activity. When the activation of MAPK was
      tested under continuous conditions by shifting plants to continuous darkness for
      a period of 72 h, the periodic rhythm persisted and followed a circadian pattern.
      Analysis of the transcripts of group A, B and C members of MAPKs under above
      conditions by quantitative real time PCR revealed that the members of group C
      exhibit periodic rhythm. Our data indicates that the MAP kinase activity in rice
      follows rhythmic expression in a circadian manner.

PMID- 19855941
TI  - [Communication of health risks: the example of HIV/AIDS prevention].
AB  - Those seeking to educate the public about health need to communicate health risks
      effectively. This involves providing evidence-based information about factors and
      behaviors that are dangerous to people's health and making recommendations
      regarding how risks can be avoided or minimized. This communication usually aims
      to motivate people to act in a way that promotes health or prevents disease.
      Organized 'health education' that seeks to communicate risks is always embedded
      in a contextual framework that in turn influences the issues and content to be
      communicated and the form of communication that is chosen. The scope of available
      scientific knowledge is an important part of this framework as is the extent to
      which risks are presented in the media as being dangerous. The media's message
      has a strong influence on how the public and specific subgroups within it react.
      The article describes conditions that contribute to successful risk communication
      based on the example of HIV/AIDS prevention. We chose this particular case
      because it can serve as an example of how to deal with future epidemics that may
      potentially generate substantial media coverage. This field report shows how risk
      communication about HIV/AIDS in the mass media in Germany in the mid-1980s
      elicited a risk consciousness among the general public that in itself was in
      danger of becoming a health risk, especially for people affected by the disease,
      and how 'health education' responded to this challenge. It concludes by
      describing how these experiences with risk communication can be applied to
      similar types of risk communication today.

PMID- 19855940
TI  - Production of ethanol and feed by high dry matter hydrolysis and fermentation of
      palm kernel press cake.
AB  - Palm kernel press cake (PKC) is a residue from palm oil extraction presently only
      used as a low protein feed supplement. PKC contains 50% fermentable hexose sugars
      present in the form of glucan and mainly galactomannan. This makes PKC an
      interesting feedstock for processing into bioethanol or in other biorefinery
      processes. Using a combination of mannanase, beta-mannosidase, and cellulases, it
      was possible without any pretreatment to hydrolyze PKC at solid concentrations of
      35% dry matter with mannose yields up to 88% of theoretical. Fermentation was
      tested using Saccharomyces cerevisiae in both a separate hydrolysis and
      fermentation (SHF) and simultaneous saccharification and fermentation (SSF)
      setup. The hydrolysates could readily be fermented without addition of nutrients
      and with average fermentation yields of 0.43 +/- 0.02 g/g based on consumed
      mannose and glucose. Employing SSF, final ethanol concentrations of 70 g/kg was
      achieved in 216 h, corresponding to an ethanol yield of 70% of theoretical or 200
      g ethanol/kg PKC. Testing various enzyme mixtures revealed that including
      cellulases in combination with mannanases significantly improved ethanol yields.
      Processing PKC to ethanol resulted in a solid residue enriched in protein from
      17% to 28%, a 70% increase, thereby potentially making a high-protein containing
      feed supplement.

PMID- 19855942
TI  - [Diseases of the visible mucosa].

PMID- 19855943
TI  - [Orogenital and conjunctival involvement in hereditary and autoimmune blistering
      diseases].
AB  - Chronic involvement of orogenital and conjunctival mucosa in the course of either
      genetically based (epidermolysis bullosa hereditaria) or auto-immunologically
      mediated (as for example pemphigus vulgaris, mucous membrane pemphigoid or
      epidermolysis bullosa acquisita) blistering diseases can cause significant
      morbidity. To provide accurate care, recognition of clinical, pathogenic and
      diagnostic features as well as awareness of recent advances in the development of
      new therapeutic modalities are mandatory and thus will be discussed in this
      review.

PMID- 19855944
TI  - [Oral manifestations of systemic diseases].
AB  - Many systemic diseases may present with oral manifestations and the oral mucosa
      may act as a mirror of internal involvement. We discuss the most common, specific
      and unspecific, as the most peculiar oral mucosal manifestations of systemic
      disease in the different organ systems. The most prevalent conditions of the oral
      mucosa in the course of HIV infection and marker lesions of multisystemic
      genodermatoses are elucidated.

PMID- 19855945
TI  - Mitochondrial involvement in cardiac apoptosis during ischemia and reperfusion:
      can we close the box?
AB  - Myocardial ischemia is the main cause of death in the Western societies.
      Therapeutic strategies aimed to protect the ischemic myocardium have been
      extensively studied. Reperfusion is the definitive treatment for acute coronary
      syndromes, especially acute myocardial infarction; however, reperfusion has the
      potential to exacerbate tissue injury, a process termed reperfusion injury.
      Ischemia/reperfusion (I/R) injury may lead to cardiac arrhythmias and contractile
      dysfunction that involve apoptosis and necrosis in the heart. The present review
      describes the mitochondrial role on cardiomyocyte death and some potential
      pharmacological strategies aimed at preventing the opening of the box, i.e.,
      mitochondrial dysfunction and membrane permeabilization that result into cell
      death. Data in the literature suggest that mitochondrial disruption during I/R
      can be avoided, although uncertainties still exist, including the fact that the
      optimal windows of treatment are still fairly unknown. Despite this, the
      protection of cardiac mitochondrial function should be critical for the patient
      survival, and new strategies to avoid mitochondrial alterations should be
      designed to avoid cardiomyocyte loss.

PMID- 19855946
TI  - Modelling Parkinson's disease in Drosophila.
AB  - The recent discovery of a number of genes involved in familial forms of
      Parkinson's disease (PD) has moved the use of model genetic organisms to the
      frontline. One avenue holding tremendous potential to find therapies against
      human diseases is the use of intact living systems where complex biological
      processes can be examined. Despite key differences that need to be taken into
      account when using invertebrate models such as Drosophila, there are many
      advantages offered by this system. The rapid generation time and the ability to
      easily generate transgenic animals together with the variety of genetic tools to
      control temporal and spatial expression of any given gene makes the fly model a
      very attractive system to study human neurodegenerative disorders. In this
      review, we analyze how the use of fruit flies has revealed to be an excellent
      tool providing valuable insights into the current understanding of the molecular
      mechanisms involved in the progression of PD.

PMID- 19855949
TI  - [Tics and Tourette's syndrome throughout the life span].
AB  - Chronic motor and vocal tics lasting longer than a year are classified as
      Tourette's syndrome (TS). Tics mostly manifest before the age of 11 years. Boys
      are affected at a threefold higher rate than girls. Tics are often worst at the
      age of 14; in 50% of the cases the tic symptoms will remit nearly completely.
      Severely affected patients often suffer from comorbidities. In childhood and
      adolescence the most common comorbid condition is attention deficit hyperactivity
      disorder (ADHD). Obsessive-compulsive behaviour, anxiety and affective disorder
      might occur in the course of TS. A dysregulation in the dopaminergic
      neurotransmission in the cortico-striatal-thalamic-cortical circuits (CSTC) might
      be the underlying neurobiological basis. The psychotropic substances administered
      for TS treatment largely affect the dopaminergic system. The most commonly used
      atypical neuroleptics are not approved for TS treatment and are used "off label".
      Atomoxetine might also improve tics in comorbid ADHD. First results of some case
      series with the partial dopamine agonist aripiprazole are encouraging.

PMID- 19855947
TI  - Phospholipases A2 and inflammatory responses in the central nervous system.
AB  - Phospholipases A2 (PLA2s) belong to a superfamily of enzymes responsible for
      hydrolyzing the sn-2 fatty acids of membrane phospholipids. These enzymes are
      known to play multiple roles for maintenance of membrane phospholipid homeostasis
      and for production of a variety of lipid mediators. Over 20 different types of
      PLA2s are present in the mammalian cells, and in snake and bee venom. Despite
      their common function in hydrolyzing fatty acids of phospholipids, they are
      diversely encoded by a number of genes and express proteins that are regulated by
      different mechanisms. Recent studies have focused on the group IV calcium
      dependent cytosolic cPLA2, the group VI calcium-independent iPLA2, and the group
      II small molecule secretory sPLA2. In the central nervous system (CNS), these
      PLA2s are distributed among neurons and glial cells. Although the physiological
      role of these PLA2s in regulating neural cell function has not yet been clearly
      elucidated, there is increasing evidence for their involvement in receptor
      signaling and transcriptional pathways that link oxidative events to inflammatory
      responses that underline many neurodegenerative diseases. Recent studies also
      reveal an important role of cPLA2 in modulating neuronal excitatory functions,
      sPLA2 in the inflammatory responses, and iPLA2 with childhood neurologic
      disorders associated with brain iron accumulation. The goal for this review is to
      better understand the structure and function of these PLA2s and to highlight
      specific types of PLA2s and their cross-talk mechanisms in these inflammatory
      responses under physiological and pathological conditions in the CNS.

PMID- 19855950
TI  - [Imaging of endoleaks after endovascular aneurysm repair (EVAR) with contrast
      enhanced ultrasound (CEUS)].
AB  - Endoleaks following endovascular aneurysm repair (EVAR) are common and present a
      diagnostic challenge in the follow-up after EVAR. Contrast-enhanced ultrasound
      (CEUS) is a promising new method for the diagnosis and follow-up of endoleaks.
      CEUS with SonoVue allows a rapid and non-invasive diagnosis in the follow-up
      after EVAR. The sensitivity and specificity of conventional ultrasound compared
      to the multislice CT angiography is estimated to be 33-63% and 63-93%,
      respectively. These values can be increased through the use of CEUS in up to 98
      100% (sensitivity) and 82-93% (specificity). This article describes the etiology,
      classification and importance of different types of endoleaks. The value of CEUS
      in this clinical scenario will be discussed.

PMID- 19855951
TI  - Development and evaluation of robust molecular markers linked to disease
      resistance in tomato for distinctness, uniformity and stability testing.
AB  - Molecular markers linked to phenotypically important traits are of great interest
      especially when traits are difficult and/or costly to be observed. In tomato
      where a strong focus on resistance breeding has led to the introgression of
      several resistance genes, resistance traits have become important characteristics
      in distinctness, uniformity and stability (DUS) testing for Plant Breeders Rights
      (PBR) applications. Evaluation of disease traits in biological assays is not
      always straightforward because assays are often influenced by environmental
      factors, and difficulties in scoring exist. In this study, we describe the
      development and/or evaluation of molecular marker assays for the Verticillium
      genes Ve1 and Ve2, the tomato mosaic virus Tm1 (linked marker), the tomato mosaic
      virus Tm2 and Tm2 ( 2 ) genes, the Meloidogyne incognita Mi1-2 gene, the Fusarium
      I (linked marker) and I2 loci, which are obligatory traits in PBR testing. The
      marker assays were evaluated for their robustness in a ring test and then
      evaluated in a set of varieties. Although in general, results between biological
      assays and marker assays gave highly correlated results, marker assays showed an
      advantage over biological tests in that the results were clearer, i.e.,
      homozygote/heterozygote presence of the resistance gene can be detected and
      heterogeneity in seed lots can be identified readily. Within the UPOV framework
      for granting of PBR, the markers have the potential to fulfil the requirements
      needed for implementation in DUS testing of candidate varieties and could
      complement or may be an alternative to the pathogenesis tests that are carried
      out at present.

PMID- 19855952
TI  - Risk of malignancies in patients with diabetes treated with human insulin or
      insulin analogues. Reply to Nagel JM, Mansmann U, Wegscheider K et al. [letter]
      and Simon D [letter].

PMID- 19855953
TI  - The long lifespan and low turnover of human islet beta cells estimated by
      mathematical modelling of lipofuscin accumulation.
AB  - AIMS/HYPOTHESIS: Defects in pancreatic beta cell turnover are implicated in the
      pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta
      cell neogenesis could contribute to diabetes. The longevity and turnover of human
      beta cells is unknown; in rodents <1 year old, a half-life of 30 days is
      estimated. Intracellular lipofuscin body (LB) accumulation is a hallmark of
      ageing in neurons. To estimate the lifespan of human beta cells, we measured beta
      cell LB accumulation in individuals aged 1-81 years. METHODS: LB content was
      determined by electron microscopical morphometry in sections of beta cells from
      human (non-diabetic, n = 45; type 2 diabetic, n = 10) and non-human primates (n =
      10; 5-30 years) and from 15 mice aged 10-99 weeks. Total cellular LB content was
      estimated by three-dimensional (3D) mathematical modelling. RESULTS: LB area
      proportion was significantly correlated with age in human and non-human primates.
      The proportion of human LB-positive beta cells was significantly related to age,
      with no apparent differences in type 2 diabetes or obesity. LB content was low in
      human insulinomas (n = 5) and alpha cells and in mouse beta cells (LB content in
      mouse <10% human). Using 3D electron microscopy and 3D mathematical modelling,
      the LB-positive human beta cells (representing aged cells) increased from >or=90%
      (<10 years) to >or=97% (>20 years) and remained constant thereafter.
      CONCLUSIONS/INTERPRETATION: Human beta cells, unlike those of young rodents, are
      long-lived. LB proportions in type 2 diabetes and obesity suggest that little
      adaptive change occurs in the adult human beta cell population, which is largely
      established by age 20 years.

PMID- 19855948
TI  - [Guideline: Treatment of obstructive sleep apnea in adults].
AB  - The current guideline discusses conservative and surgical therapy of obstructive
      sleep apnea (OSA) in adults from the perspective of the ear, nose and throat
      specialist. The revised guideline was commissioned by the German Society of Ear
      Nose-Throat, Head-Neck Surgery (DG HNO KHC) and compiled by the DG HNO KHC's
      Working Group on Sleep Medicine. The guideline was based on a formal consensus
      procedure according to the guidelines set out by the German Association of
      Scientific Medical Societies (AWMF) in the form of a"S2e guideline". Research of
      the literature available on the subject up to and including December 2008 forms
      the basis for the recommendations. Evaluation of the publications found was made
      according to the recommendations of the Oxford Centre for Evidence-Based Medicine
      (OCEBM). This yielded a recommendation grade, whereby grade A represents highly
      evidence-based studies and grade D those with a low evidence base.

PMID- 19855954
TI  - Mortality in very long-stay pediatric intensive care unit patients and incidence
      of withdrawal of treatment.
AB  - BACKGROUND: The mortality for children with prolonged stay in pediatric intensive
      care units (PICU) is much higher than overall mortality. The incidence of
      withdrawal or limitation of therapy in this group is unknown. PURPOSE: To assess
      mortality and characteristics of children admitted for >or=28 days to our ICU,
      and to describe the extent to which limitations of care were involved in the
      terminal phase preceding death. METHODS: For the period 2003 to 2005 clinical
      data were collected retrospectively for children with prolonged stay (defined as
      >or=28 days) in a medical/surgical PICU of a university children's hospital.
      RESULTS: In the PICU, 4.4% of the children (116/2,607, equal gender, mean age 29
      days) had a prolonged stay. Median (range) stay was 56 (28-546) days. These
      children accounted for 3% of total admissions and occupied 63% of total admission
      days. Mortality during admission for this group was five times higher (22%) than
      the average PICU mortality rate of 4.6%. Withdrawal or limitation of therapy
      preceded 70% of deaths. CONCLUSIONS: Children with prolonged stay in the PICU
      have a significantly high risk of mortality. Death is typically preceded by
      limitation of care.

PMID- 19855955
TI  - Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients
      with acute lung injury.
AB  - PURPOSE: Deposition of fibrin in the alveolar space is a hallmark of acute lung
      injury (ALI). Plasminogen activator inhibitor-1 (PAI-1) is an antifibrinolytic
      agent that is activated during inflammation. Increased plasma and pulmonary edema
      fluid levels of PAI-1 are associated with increased mortality in adults with ALI.
      This relationship has not been examined in children. The objective of this study
      was to test whether increased plasma PAI-1 levels are associated with worse
      clinical outcomes in pediatric patients with ALI. DESIGN/METHODS: We measured
      plasma PAI-1 levels on the first day of ALI among 94 pediatric patients enrolled
      in two separate prospective, multicenter investigations and followed them for
      clinical outcomes. All patients met American European Consensus Conference
      criteria for ALI. RESULTS: A total of 94 patients were included. The median age
      was 3.2 years (range 16 days-18 years), the PaO(2)/F(i)O(2) was 141 +/- 72 (mean
      +/- SD), and overall mortality was 14/94 (15%). PAI-1 levels were significantly
      higher in nonsurvivors compared to survivors (P < 0.01). The adjusted odds of
      mortality doubled for every log increase in the level of plasma PAI-1 after
      adjustment for age and severity of illness. CONCLUSIONS: Higher PAI-1 levels are
      associated with increased mortality and fewer ventilator-free days among
      pediatric patients with ALI. These findings suggest that impaired fibrinolysis
      may play a role in the pathogenesis of ALI in pediatric patients and suggest that
      PAI-1 may serve as a useful biomarker of prognosis in patients with ALI.

PMID- 19855957
TI  - Improving acid-base evaluation: the proper use of the old tools.

PMID- 19855958
TI  - Application of tissue-engineered cartilage with BMP-7 gene to repair knee joint
      cartilage injury in rabbits.
AB  - Injured articular cartilage has a poor capacity for spontaneous healing. So far,
      satisfactory solution to this subsistent problem has not been found, but
      transgenic therapy may be a promising way. This study aims to evaluate the
      effectiveness of a tissue-engineered cartilage that was transfected with
      morphogenetic protein 7 (BMP 7) in repairing the cartilaginous defects of rabbit
      knee joints. Chondrocytes were transfected with BMP-7 gene (5 x 10(6) cells/ml),
      inoculated into the collagen-fibrin gel scaffolds, and cultured for 14 days.
      Then, the scaffolds were implanted onto the created defects (5.0 mm in diameter)
      in rabbits' knee joints. After 12 weeks, the rabbits were sacrificed and
      histological sections were evaluated using modified O'Driscoll cartilage scores;
      In situ hybridization and immunohistochemistry were performed to detect the
      expression of BMP-7 mRNA and BMP-7 at the implanted site while the content of DNA
      and GAG was determined as well. A better quality of repairs was observed at the
      12th week after implantation when compared to the control group using
      histological analyses. The content of DNA and specific secretion of GAG in the
      treatment group is statistically significant different compared with the control
      group. Gene therapy may be a promising treatment method, but the novel therapy
      approach needs further studies with respect to a longer follow-up period.

PMID- 19855959
TI  - Comparison of the metabolic activities of four wild-type Clostridium perfringens
      strains with their gatifloxacin-selected resistant mutants.
AB  - The production of short-chain fatty acids, reductive enzymes, and hydrolytic
      enzymes by four gatifloxacin-selected, fluoroquinolone-resistant, mutant strains
      of C. perfringens, with stable mutations either in DNA gyrase or in both DNA
      gyrase and topoisomerase IV, was compared with that produced by the wild-type
      parent strains to investigate the effect of mutations associated with the
      selection of gatifloxacin resistance on bacterial metabolic activities. The
      mutants differed from their respective wild-type parent strains in the enzymatic
      activities of azoreductase, nitroreductase, and beta-glucosidase and in the ratio
      of butyric acid to acetic acid production. Microarray analysis of one wild type
      and the corresponding mutant revealed different levels of mRNA expression for the
      enzymes involved in short-chain fatty acid (SCFA) synthesis and for beta
      glucosidase and oxidoreductases. In addition to mutations in the target genes,
      selection of resistance to gatifloxacin resulted in strain-specific physiological
      changes in the resistant mutants of C. perfringens that affected their metabolic
      activities.

PMID- 19855961
TI  - Establishment of a system based on universal multiplex-PCR for screening
      genetically modified crops.
AB  - The rapid development of many genetically modified (GM) crops in the past two
      decades makes it necessary to introduce an alternative strategy for routine
      screening and identification. In this study, we established a universal multiplex
      PCR detection system which will effectively reduce the number of reactions needed
      for sample identification. The PCR targets of this system include the six most
      frequently used transgenic elements: cauliflower mosaic virus (CaMV) 35S
      promoter, Agrobacterium tumefaciens nopaline synthase (nos) promoter,
      Agrobacterium tumefaciens nopaline synthase (nos) terminator, the neomycin
      phosphotransferase II (nptII) gene, the 5-enolpyruvylshikimate-3-phosphate
      synthase (CP4 epsps) gene of Agrobacterium tumefaciens strain CP4, and the
      phosphinothricin N-acetyltransferase (pat) gene. According to the AGBIOS
      database, the coverage of this detection system is 93% of commercial GM crops.
      This detection system could detect all certified reference materials (CRMs) at
      the 1.0% level. The correct combination of all the CRM amplicon patterns proved
      the specificity of this multiplex PCR system. Furthermore, the amplicon patterns
      of this multiplex PCR detection system could be used as an index of
      classification which will narrow the range of possible GM products. The
      simulation result of this multiplex PCR detection system on all commercialized
      139 GM products in the AGBIOS database showed that the maximum number of PCR
      reactions needed to identify an unknown sample can be reduced to 13. In this
      study, we established a high-throughput multiplex PCR detection system with
      feasible sensitivity, specificity, and cost. By incorporating this detection
      system, the routine GM crop-detection process will meet the challenges resulting
      from a rapid increase in the number of GM crops in the future.

PMID- 19855960
TI  - Vasodilator effects of Diocleinae lectins from the Canavalia genus.
AB  - This study investigated and compared vascular actions of leguminous lectins
      obtained from the Canavalia genus (Canavalia brasiliensis, Canavalia gladiata,
      and Canavalia maritima) in the rat models of paw edema and isolated aorta. Paw
      edema was induced by subcutaneous injection of lectins (0.01-1 mg/kg) in animals
      pre-treated or not with indomethacin or L-NAME. In isolated aorta, cumulative
      concentration curves of C. gladiata or C. brasiliensis (1-100 microg/ml) were
      performed at the contraction plateau induced by phenylephrine or at tissue basal
      tonus. The mechanism of the lectin relaxant action was investigated by previous
      addition of L-NAME, indomethacin, or tetraethylammonium. In both models, the
      lectin domain involvement was evaluated by incubation of lectins with their
      ligand and non-ligand sugars. The lectins induced paw edema paralleled by protein
      leakage. The edematogenic activity elicited by C. gladiata and C. brasiliensis
      involves prostaglandins and nitric oxide (NO), while that of C. maritima occurs
      without NO interference. C. gladiata and C. brasiliensis elicited aorta
      relaxation involving NO and prostacyclin, while that of C. gladiata included
      EDHF. All lectin effects were prevented by their binding sugars. The present
      study demonstrated important vasodilator effects of different degrees and
      mechanisms in vivo and in vitro of Canavalia lectins. In vivo, the edematogenic
      activity was paralleled by plasma exudation, and in vitro, aorta relaxation was
      strictly dependent on intact endothelium. All effects occurred via interaction
      with lectin domains and participation of NO and/or prostanoids.

PMID- 19855962
TI  - LC-ESI MS/MS quantification of atropine and six other antimuscarinic tropane
      alkaloids in plasma.
AB  - We have developed and validated a quantitative liquid chromatography electrospray
      ionization tandem mass spectrometry (LC-ESI MS/MS) procedure for the simultaneous
      determination of seven natural and semisynthetic tropane alkaloids in plasma:
      atropine (d-hyoscyamine/l-hyoscyamine), cocaine, homatropine, ipratropium,
      littorine, N-butylscopolamine, and scopolamine. Plasma and serum samples were
      precipitated for deproteinization (recovery 88-94%), followed by reversed-phase
      based liquid chromatography prior to positive electrospray ionization for
      detection by multiple reaction monitoring using a linear ion trap quadrupole mass
      spectrometer. All analytes were quantified using cocaine-d3 as an internal
      standard suitable and reliable for robust, precise (coefficient of variation 2
      13%), and accurate (87-122%) measurement within a linear range of 3 orders of
      magnitude (0.05-50 ng/ml plasma). The method was exemplarily applied to stability
      studies in phosphate-buffered saline, human serum, and rabbit serum. Each
      alkaloid was incubated separately and samples were taken at distinct incubation
      time points. Supernatants of diverse alkaloids at corresponding time points were
      pooled and subjected to simultaneous LC-ESI MS/MS quantification. This
      combinatorial analysis design allowed us to analyze the stability of samples with
      a drastically reduced number of chromatographic runs. In the presence of rabbit
      serum, all tropane alkaloids tested were degraded significantly within minutes to
      hours, with the exception of the stable semisynthetic compounds ipratropium and N
      butylscopolamine. In contrast, in the presence of equal concentrations of human
      serum, no degradation was observed for any of the compounds, with the exception
      of cocaine. Relevant enzymes involved in enzymatic degradation are discussed.

PMID- 19855963
TI  - A practical approach to screen for authorised and unauthorised genetically
      modified plants.
AB  - In routine analysis, screening methods based on real-time PCR are most commonly
      used for the detection of genetically modified (GM) plant material in food and
      feed. In this paper, it is shown that the combination of five DNA target
      sequences can be used as a universal screening approach for at least 81 GM plant
      events authorised or unauthorised for placing on the market and described in
      publicly available databases. Except for maize event LY038, soybean events DP
      305423 and BPS-CV127-9 and cotton event 281-24-236 x 3006-210-23, at least one of
      the five genetic elements has been inserted in these GM plants and is targeted by
      this screening approach. For the detection of these sequences, fully validated
      real-time PCR methods have been selected. A screening table is presented that
      describes the presence or absence of the target sequences for most of the listed
      GM plants. These data have been verified either theoretically according to
      available databases or experimentally using available reference materials. The
      screening table will be updated regularly by a network of German enforcement
      laboratories.

PMID- 19855964
TI  - Homeostasis of peripheral FoxP3(+) CD4 (+) regulatory T cells in patients with
      early and late stage breast cancer.
AB  - FoxP3( + ) CD4( + ) regulatory T cells (Tregs) are important mediators of
      peripheral immune tolerance, acting via multiple mechanisms to suppress cellular
      immunity including antitumor responses. Although therapeutic strategies have been
      proposed to deplete Tregs in patients with breast cancer and other malignancies,
      dynamic changes in the Treg compartment as a function of stage and treatment of
      breast cancer remain poorly understood. Here, we evaluated peripheral blood
      CD4(+) T cells and FoxP3(+) CD4(+) T cells from 45 patients with early or late
      stage breast cancer and compared percentages, absolute counts, and Treg function
      to those from healthy volunteers (HV) of comparable age. Patients having
      completed adjuvant chemotherapy and patients with metastatic cancer exhibited
      significantly lower absolute CD4 counts and significantly higher percentages of
      FoxP3(+) CD4(+) T cells. In contrast, the absolute counts of circulating FoxP3(+)
      CD4(+) T cells did not differ significantly among early stage patients, late
      stage patients, or HV. Functionally, FoxP3(+) CD4(+) T cells from all donor
      groups similarly expressed CTLA-4 and failed to secrete IFN-gamma in response to
      stimulation. Thus, although Tregs comprise an increased percentage of circulating
      CD4(+) T cells in patients with metastatic breast cancer and patients in
      remission after completing the adjuvant chemotherapy, the systemic Treg pool, as
      measured by absolute counts, appears relatively constant regardless of disease
      stage or treatment status. Total CD4(+) T cell counts are not constant, however,
      suggesting that homeostatic mechanisms, or susceptibility to cytotoxic or
      malignant insults, fundamentally differ for regulatory and non-regulatory CD4(+)
      T cells.

PMID- 19855965
TI  - Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic
      remission after treatment with lenalidomide have an increased risk for clonal
      evolution and AML progression.
AB  - Lenalidomide consistently induces transfusion independence and complete
      cytogenetic response in patients with myelodysplastic syndromes with 5q deletion.
      Only limited information on long-term outcome is currently available. We
      performed a long-term follow-up analysis of 42 patients with low or intermediate
      risk myelodysplastic syndromes and 5q deletion treated with lenalidomide. At a
      median follow-up of 40 months, 58% of the patients achieved an erythroid response
      and 48% a cytogenetic response. Thirty-six percent of patients progressed into
      acute myeloid leukaemia. Most of them (87%) acquired chromosome aberrations in
      addition to the 5q deletion, i.e. underwent clonal evolution during
      leukaemogenesis. There were no clinical, cytological or cytogenetic markers at
      study entry that allowed prediction of increased risk of leukaemic
      transformation. However, erythroid and cytogenetic responders had a significantly
      decreased risk of progression to acute myeloid leukaemia (p = 0.001 and p =
      0.009, respectively) compared to non-responders. Three and 5 years after study
      entry, the cumulative incidence of acute myeloid leukaemia for patients with a
      cytogenetic response was 10% and 21%, respectively, and for patients without
      cytogenetic response, it was 46% and 60%. Patients with del(5q) myelodysplastic
      syndromes without erythroid or cytogenetic remission after treatment with
      lenalidomide have a high risk for clonal evolution and acute myeloid leukaemia
      progression. In refractory, or relapsing, patients, genetic instability and
      clonal evolution seem to be the driving forces of leukaemic transformation.
      Regular follow-up investigations of del(5q) myelodysplastic syndrome patients
      treated with lenalidomide may help to identify patients requiring alternative
      treatment strategies.

PMID- 19855966
TI  - A phase I study of imexon plus gemcitabine as first-line therapy for advanced
      pancreatic cancer.
AB  - PURPOSE: Imexon is an aziridine-derived iminopyrrolidone which has synergy with
      gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy
      for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to
      evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD)
      in patients with advanced pancreatic cancer. METHODS: Patients with untreated
      locally advanced or metastatic pancreatic adenocarcinoma received therapy in
      sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously
      (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30
      min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2)
      IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min
      on days 1, 8, and 15 every 28 days). RESULTS: One hundred five patients received
      340 treatment cycles (median 2, range 1-16). PATIENT CHARACTERISTICS: median age
      63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and
      pain, often with transient, acute diarrhea. Best response was confirmed partial
      response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There
      was a dose proportional increase in imexon AUC across the doses tested with
      terminal half life 69 min at the MTD and no alteration of gemcitabine
      pharmacokinetics. CONCLUSIONS: The recommended phase II dose of imexon is 875
      mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and
      cramping. Encouraging antitumor responses support further evaluation of this
      combination in advanced pancreatic cancer.

PMID- 19855967
TI  - Medulloblastoma in childhood: revisiting intrathecal therapy in infants and
      children.
AB  - INTRODUCTION: Intrathecal chemotherapy is being explored in medulloblastoma in
      pre-school children as part of brain-sparing strategies and as an alternative to
      unacceptably neurotoxic cranio-spinal radiotherapy. The range of drugs suitable
      for this route of administration is restricted by the lack of research evidence
      of pharmacological suitability and efficacy of other drugs in medulloblastoma.
      METHODS: Ideal clinical, biological, physicochemical and pharmaceutical
      properties for intrathecal administration were defined through literature review
      of pharmaceutical texts, Medline, Embase and consulting the manufacturers. A
      total of 126 chemotherapy agents were assessed against these criteria by
      searching the academic domain of pharmaceutical texts, computer databases and
      consultation with manufacturers. RESULTS: Of the 126 candidate drugs, 99 were
      rejected because of documentation of their irritant nature, neurotoxicity and
      requirement for hepatic activation in standard pharmaceutical texts. Fifty were
      rejected for a single identifiable reason including, neurotoxicity (n = 24),
      irritant (n = 15), needs enzyme activation (n = 5), clinical evidence of
      intrathecal neurotoxicity (n = 4) and no evidence of tumour-specific efficacy (n
      = 2). Where two reasons were cited the justifications were: neurotoxic and
      irritant (n = 3) and needs activation and systemic administration results in
      equivalent concentration (n = 1). Twenty-seven drugs remained of which 12 were
      selected as eligible for further clinical investigation, and 15 were selected for
      further pre-clinical investigation. CONCLUSIONS: The pre-determined criteria were
      not applicable, in their entirety, in the majority of drugs, due to lack of
      information in the academic domain, emphasising the importance of a more open
      approach for sharing basic drug information. The prioritised list of 12 candidate
      drugs for clinical trial and 15 for pre-clinical investigation justify that a
      concerted research effort in this area of practice is made.

PMID- 19855968
TI  - Dermatomyositis and HIV infection: case report and review of the literature.
AB  - Since the 1980s, a host of autoimmune phenomena and rheumatologic illnesses have
      been linked to infection with the human immunodeficiency virus (HIV). Given the
      broad effects of this virus on both the humoral and cell-mediated arms of the
      immune system, illnesses such as polymyositis and Reiter's syndrome appear to be
      more prevalent in HIV-infected individuals and occur in the absence of well
      described predispositions. The activities of some rheumatologic illnesses exhibit
      an inverse relationship with the course of HIV infection, such as rheumatoid
      arthritis, which becomes more quiescent with advancing disease. Dermatomyositis
      is a rheumatologic illness that very infrequently occurs and during our review of
      literature only three other cases were reported. We present the case of a
      Caucasian male in his mid-20s who presented with acquired immunodeficiency
      syndrome and subsequently developed dermatomyositis. In this review, we highlight
      the current relationship between HIV infection and autoimmunity, the possible
      ways HIV infection may foster an environment favorable for the development of
      dermatomyositis, and review the previously reported cases of individuals with HIV
      infection who developed dermatomyositis. The complex issues of how to treat
      individuals with HIV and dermatomyositis is also discussed.

PMID- 19855969
TI  - Rheumatoid arthritis in patient with homozygous haemoglobin C disease.
AB  - To date, few cases of hemoglobinopathies in patients with rheumatoid arthritis
      (RA) have been reported (Marino and Mcdonald in J Rheumatol 17:970-972, 1990;
      Gladman and Bombardier in Arthritis Rheum 30:1065-1068, 1987; Michel et al. in
      Semin Arthritis Rheum 38:228-240, 2008). These haemoglobin diseases are
      associated with characteristics abnormalities of the skeleton. Haemoglobin C
      disease is a benign hemoglobinopathy rarely associated with skeletal disorders
      [Pieron et al. in la semaine des hopitaux 57(1-2):22-25, 1981]. We report a case
      of RA in a 60-year-old woman with homozygous haemoglobin C disease. This
      coexistence may be a pure coincidence, although we discuss the difficulties with
      RA treatment in this case due to the unknown effect of anti-rheumatic drugs on
      the progression of haemoglobin C disease.

PMID- 19855970
TI  - Digital ulcers as the first manifestation of carpal tunnel syndrome.
AB  - While carpal tunnel syndrome (CTS) is the most common entrapment neuropathy
      presented at rheumatologic consultation, its ulcerative variant is rarely
      described. We report of a case of severe bilateral medial nerve palsy, presented
      to us for diagnosis of chronic digital ulcers which had been suspected to be
      rheumatologic in origin. Careful examination revealed an unusual case of CTS in
      an advanced stage, which presented itself with skin changes only, lacking all the
      typical neurologic symptoms or rheumatologic background. Our case stresses the
      importance for rheumatologists to be aware of the ulcerative form of CTS as one
      of the etiologic differential diagnostic options of digital ulcers.

PMID- 19855971
TI  - Two rare involvement sites: synovial chondromatosis.
AB  - Synovial chondromatosis (SC) is a rarely encountered benign disease of unknown
      etiology characterized by multiple joint mouse, as well as metaplastic cartilage
      points in the joint, bursa and tendon sheaths. Although single joint involvement
      is frequently encountered, multiple joint involvements may also occur. In this
      study, two patients with SC in the right shoulder joint and in both ankles were
      presented, reviewed according to literature.

PMID- 19855972
TI  - Serum melatonin levels in ankylosing spondilitis: correlation with disease
      activity.
AB  - This study was carried out to determine the serum levels of melatonin (MLT) in
      patients with ankylosing spondilitis (AS) and to evaluate its correlation with
      disease activity. We assessed clinical characteristics and labaratory parameters.
      Serum samples from 36 patients (25 males, 11 females) with active AS and 25
      healthy subjects (18 males, 7 females) were collected. MLT levels were measured
      by enzyme-linked immunosorbent assay, and disease activity of AS was assessed
      according to the Bath AS disease activity index (BASDAI), the erythrocyte
      sedimentation rate (ESR), and C-reactive protein (CRP). Then, the results were
      compared with those from 25 healty controls. The serum levels of MLT were
      significantly increased in AS patients as compared to healthy controls (p <
      0.05). MLT levels were correlated with BASDAI (r = 0.871, p < 0.001) and CRP
      levels (r = 0.691, p < 0.001), but not with ESR, in patients with AS. Our results
      suggest a possible role for this immunoregulatory hormone in the disease activity
      in AS patients.

PMID- 19855973
TI  - Exercise-induced rhabdomyolysis and transient loss of deambulation as outset of
      partial carnitine palmityl transferase II deficiency.
AB  - We report the case of a 13-year-old boy with an abrupt onset of leg pain and
      muscle weakness, incapability of deambulation and a laboratory picture of
      exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced
      diuresis were adopted to avoid renal complications. No evidence of articular or
      residual muscular damage was appreciated in the short-term. The recurrence of
      rhabdomyolysis required a muscular biopsy showing a disturbance of fatty acid
      beta-oxidation pathway.

PMID- 19855974
TI  - Uncommon case of ankylosing spondylitis associated with spontaneous occurring
      hypoparathyroidism.
AB  - Hypoparathyroidism and ankylosing spondylitis are two conditions with distinctive
      features which allow their differentiation. Hypoparathyroidism can be responsible
      for clinical and radiological changes resembling those seen in patients with
      ankylosing spondylitis. We report an exceptional case of a patient with an
      association between ankylosing spondylitis and a severe idiopathic
      hypoparathyroidism with difficulties in diagnosis. To our knowledge, this is the
      first case of such an occurrence.

PMID- 19855975
TI  - Endothelial dysfunction in Iranian lupus patients.
AB  - Atherosclerosis has a high prevalence in systemic lupus erythematosus (SLE)
      patients and vascular endothelial dysfunction is the earliest stage of
      atherosclerosis. The aim of this study was to evaluate the prevalence of vascular
      endothelial dysfunction and its risk factors in SLE patients and to identify its
      correlation with disease activity, duration and concomitant conditions in these
      patients. A total of 84 female SLE patients and 18 healthy young women were
      included. The vascular endothelial function was evaluated via ultrasonographic
      assessment of the brachial artery diameter to determine flow-mediated dilation
      (FMD) and post-TNG dilation-FMD gap (PFG) indexes. FMD indexes of one standard
      deviation lower than mean FMD of the control group were considered as impaired,
      and PFG indexes of one standard deviation more than mean PFG of the control group
      were defined as impaired. SLE patients had a higher prevalence of impaired FMD
      than healthy subjects (48.8 vs. 5.5%). The prevalence of impaired PFG in SLE
      cases and healthy subjects was 25 and 5.5%, respectively. FMD and PFG impairment
      did not have any significant correlation with disease activity, duration,
      presence of anti-dsDNA, anticardiolipin antibodies, antiphospholipid syndrome and
      history of receiving cyclophosphamide pulses. Vascular endothelial dysfunction is
      very common in SLE patients and no single specific factor can explain this
      finding. We recommend the application of brachial artery Doppler ultrasound as a
      screening test for detection of early stages of atherosclerosis in SLE patients.

PMID- 19855977
TI  - Fgf10 gene expression is delayed in the embryonic lung mesenchyme in the
      adriamycin mouse model.
AB  - BACKGROUND: The adriamycin mouse model is a well-established teratogenic model of
      esophageal atresia/tracheoesophageal fistula. Fibroblast growth factor 10 (Fgf10)
      plays a key role in branching of the lung buds during lung morphogenesis. Fgf10
      knockout mice exhibit the absence of the lungs. Optical projection tomography
      (OPT) is a technique that allows three-dimensional (3D) imaging of gene
      expression in small tissue specimens in an anatomical context. The aim of this
      study was to investigate the temporo-spatial expression of Fgf10 during the
      critical period of separation of the trachea and esophagus in normal and
      adriamycin-treated embryos using OPT. METHODS: Time-mated CBA/Ca mice received
      intraperitoneal injections of adriamycin (6 mg/kg) or saline on days 7 and 8 of
      gestation. Embryos were harvested on days 10-13, stained after whole mount in
      situ hybridization with labeled RNA probes to detect Fgf10 transcripts (n = 5 for
      each treatment/day of gestation). Immunolocalization with endoderm marker Hnf3
      beta was used to visualize morphology. Embryos were scanned by OPT to obtain 3D
      representations of gene expression domains. RESULTS: Computer reconstructed
      specimens allowed precise staging of developing embryos according to Theiler
      Staging (TS) criteria. OPT elegantly displayed Fgf10 gene expression in the
      pulmonary mesenchyme around the tip of the lung buds in both controls and treated
      embryos in the same spatial territory. Fgf10 gene expression was first detected
      in the control embryos at TS17. However, Fgf10 gene expression in adriamycin
      treated embryos was first only observed at TS18 in 67% of the specimens.
      CONCLUSION: Delayed Fgf10 gene expression during the critical period of
      separation of the trachea and esophagus may affect lung bud formation in the
      adriamycin model leading to tracheoesophageal malformations.

PMID- 19855976
TI  - Sildenafil citrate and tamsulosin combination is not superior to monotherapy in
      treating lower urinary tract symptoms and erectile dysfunction.
AB  - PURPOSE: To evaluate the efficacy of sildenafil citrate only, 25 mg. Four
      times/week, tamsulosin only, 0.4 mg once daily, and the combination of both on
      lower urinary tract symptoms (LUTS) suggestive of benign prostate hyperplasia
      (BPH) and erectile dysfunction. METHODS: A total of 60 men with BPH-related LUTS
      were randomized to receive sildenafil citrate only (n = 20), tamsulosin only (n =
      20), and the combination of both (n = 20) for 8 weeks. Changes from baseline in
      International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q (max)),
      post voiding residual urine volume (PRV), Sexual Health Inventory for Male (SHIM)
      score, 3rd and 4th questions of International Index of Erectile Function (IIEF)
      were assessed at the end of the treatment. RESULTS: The mean age was 58 years.
      IPSS, Q (max), PRV, SHIM scores, and 3rd and 4th questions in IIEF significantly
      improved in each group. Improvement of IPSS was more remarkable in combination
      (40.1%) and tamsulosin only (36.2%) groups in comparison with sildenafil citrate
      only group (28.2%; p < 0.001). Improvement of Q (max) and PRV were greater in
      tamsulosin only and combination than sildenafil citrate only group. SHIM scores
      significantly improved in sildenafil citrate only (65%) and combination (67.4%)
      than tamsulosin only (12.4%; p < 0.001). Increases in the 3rd and 4th questions
      of IIEF were greater in sildenafil only and combination than tamsulosin only (p <
      0.001). CONCLUSIONS: Treatment with the combination of tamsulosin only and
      sildenafil citrate only was not superior to tamsulosin only to enhance voiding
      symptoms. Also, sexual function improvement was similar for both the combination
      and sildenafil citrate only treatments.

PMID- 19855978
TI  - Microscopic magnetic resonance in congenital diaphragmatic hernia and associated
      malformations in rats.
AB  - BACKGROUND/AIM: The research on congenital diaphragmatic hernia (CDH) is often
      carried out on the nitrofen fetal rat model in which most investigations involve
      microdissections and fastidious assessment of serial sections of different
      anatomic areas. Current microscopic magnetic resonance (MMR) equipment allows
      detailed anatomic studies of alive, fresh or fixed fetuses. The purpose of the
      present study was to demonstrate that CDH itself and most of the associated
      malformations are adequately imaged and measured by MMR. MATERIALS AND METHODS:
      Fetuses from pregnant rats treated with either i.g. vehicle (control, n = 10) or
      100 mg nitrofen (only those with CDH, n = 18) on E9.5 were recovered on E21 (term
      = E22) and total body was scanned by MMR under sedation in a 7 T MRI system
      (Bruker Medical, Ettlingen, Germany). CDH was detected with a coronal multislice
      fast spin echo sequence with a long repetition time and short effective echo
      time. Oblique MPR and 3D reconstructions were used. All studies were processed
      with attention to the hernia and its contents and the structure of the
      tracheobronchial tree and the lung, the heart and great vessels, the thymus and
      cervico-thoracic vertebrae. The findings in both groups were compared. RESULTS:
      Congenital diaphragmatic hernia, lung hypoplasia and parenchymal features were
      clearly depicted. Tracheal ring anomalies were also demonstrated. The thymus was
      significantly smaller in CDH pups (2.9 x 1 x 2.4 mm) than in controls (4 x 1.3 x
      2.8 mm) (p < 0.01). MRI was particularly performant for imaging cardiovascular
      anomalies: 4 double aortic arches, 3 Fallots, 3 right aortic arches, 3
      ventricular septal defects and 1 aberrant subclavian artery. CONCLUSIONS:
      Microscopic magnetic resonance involves refined and expensive equipment but it
      provides a powerful research tool for the study of CDH and other malformations in
      rat fetuses. Further work on this area is warranted.

PMID- 19855979
TI  - Loss of intestine during stoma closure: an experimental model comparing
      laparoscopic and conventional techniques.
AB  - PURPOSE: This study compared laparoscopy-assisted stoma closure (Lap) with
      conventional closure (Co) to assess loss of intestine. METHODS: Ileostomies (loop
      L; single S) were performed 5 cm proximal to the ileocecal junction through a
      right lower quadrant incision in forty 11-week-old Lewis rats (L = 20, S = 20).
      Stoma closure was performed 60 days later using laparoscopy (Lap) or conventional
      closure (Co) in 10 rats each, to give 4 groups, Lap-L, Lap-S, Co-L, and Co-S. End
      to-end anastomosis was performed through the stoma site in all rats. Bowel
      resected from the skin to the anastomosis was termed resected unusable bowel
      (RUB) and measured blindly. Laparotomy was performed 30 days later to assess the
      status of the anastomosis and complications. RESULTS: Average RUB with Lap was
      significantly shorter; Lap-L (17.8 mm) versus Co-L (23.8 mm), P = 0.002, and Lap
      S (10.6 mm) versus Co-S (13.8 mm), P = 0.001. During Co, accidental full
      thickness injury to underlying bowel during stoma take-down occurred in 3 Co-L
      and 2 Co-S rats. All Lap rats were uncomplicated. Average times taken until end
      of stoma take-down were 6.1 min for Lap-L (3.2 min for trocar insertion, 2.8 min
      for stoma take-down), 5.6 min for Lap-S (2.8 and 2.7 min), 6.3 min for Co-L (from
      first incision to stoma take-down), and 5.1 min for Co-S (P = NS). At laparotomy
      there was no evidence of complications such as wound infection, incisional hernia
      or anastomotic stenosis in any rat. CONCLUSIONS: Our results suggest that
      laparoscopy-assisted stoma closure is safe and quick, and results in less loss of
      intestine during stoma closure.

PMID- 19855980
TI  - Fluorescence-activated cell sorting of PCK-26 antigen-positive cells enables
      selection of ovine esophageal epithelial cells with improved viability on
      scaffolds for esophagus tissue engineering.
AB  - OBJECTIVE: For esophagus tissue engineering, isolation and proliferation of
      esophageal epithelial cells (EEC) is a pre-requisite for scaffold seeding to
      create constructs. The aim of this study was to sort EEC expressing cytokeratin
      markers and their proliferative subpopulations; also, to investigate the
      viability of differentiated EEC subpopulations on collagen scaffolds. METHODS:
      Ovine esophageal epithelial cells (OEECs) from sheep esophagus were analyzed
      using flow cytometry for pan cytokeratin (PCK-26) and proliferation cell nuclear
      antigen (PCNA). Using fluorescent-activated cell sorting, OEEC were separated and
      analyzed for PCNA expression. The OEEC subpopulations were seeded on collagen
      scaffolds for a week in vitro culture. RESULTS: Proliferation cell nuclear
      antigen was expressed in >45% of OEEC isolated. In flow cytometry, 30% OEEC were
      PCK-26 positive which exhibited a high-proliferative capacity of 80%. PCK-26
      negative OECC exhibited a low-proliferative capability of 13%. Scanning electron
      microscopy demonstrated organized attachment and uniform scaffold coverage in PCK
      26-positive cells. CONCLUSION: Ovine esophageal epithelial cells can be divided
      into PCK-26-positive and negative subpopulations. PCK-26-positive OEEC constitute
      one-third of the isolated cells with high-proliferative capability. Seeding of
      PCK-26-positive OEEC on collagen scaffolds leads to uniform distribution of cells
      in vitro. In esophagus, tissue engineering PCK-26-positive OEEC subpopulation is
      important for optimal construct generation.

PMID- 19855981
TI  - Is C-reactive protein a reliable test for suspected appendicitis in extremely
      obese children?
AB  - PURPOSE: The diagnosis of acute appendicitis by physical examination can
      sometimes be difficult in extremely obese children. C-reactive protein (CRP) is
      commonly used to support the clinical diagnosis of appendicitis. However, obesity
      has been widely recognized as a chronic inflammatory condition and associated
      with elevated inflammatory indicators including CRP. The aim of this study was to
      examine the association between obesity and CRP levels in extremely obese
      children presenting with suspected appendicitis. MATERIALS: The hospital records
      of 947 consecutive patients, who underwent appendectomy for acute appendicitis
      between 2002 and 2008 were retrospectively analyzed. 164 children (17.3%) were
      extremely obese. Extreme obesity was defined, as greater than two standard
      deviations above the standardized mean weight for age. The diagnostic value of
      CRP level was compared between extremely obese and non-obese children. RESULTS:
      The incidence of histologically normal appendix was significantly higher in
      extremely obese children [42 out of 164 (25.6%)] compared to non-obese children
      [85 out of 783 (10.8%) (P < 0.001)]. The mean CRP levels were significantly
      higher in extremely obese children with histologically normal appendix compared
      to non-obese children with normal appendix (P < 0.001). The specificity and the
      positive predictive value were significantly lower in the extremely obese
      children group than in the non-obese group (P < 0.001). CONCLUSION: CRP is not a
      reliable marker of inflammation in extremely obese children presenting with
      suspected appendicitis. Our data highlight the importance of obesity when
      interpreting the significance of an elevated CRP level in children with suspected
      diagnosis of appendicitis.

PMID- 19855982
TI  - Effect of simvastatin on intestinal recovery following gut ischemia-reperfusion
      injury in a rat.
AB  - BACKGROUND: Pleiotropic (lipid lowering-independent) effects of statins are
      attributed to their antiinflammatory, antioxidant, and/or vascular actions.
      Extensive studies in various experimental models have established that
      pretreatment with simvastatin significantly protects heart and kidney injured by
      ischemia-reperfusion (IR). The purpose of the present study was to examine the
      effect of simvastatin on intestinal recovery and enterocyte turnover after
      intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into
      three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats
      underwent occlusion of both superior mesenteric artery and portal vein for 30 min
      followed by 48 h of reperfusion, and (3) IR-SIM rats underwent IR and were
      treated with oral simvastatin (10 mg/kg) given by gavage immediately before and
      24 h after operation. Intestinal structural changes, Park's injury score,
      enterocyte proliferation and enterocyte apoptosis were determined 24 h following
      IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis
      with P less than 0.05 considered statistically significant. RESULTS: Treatment
      with simvastatin resulted in a significant increase in bowel and mucosal weight
      in ileum, villus height and crypt depth in jejunum and ileum compared to IR
      animals. IR-SIM rats had also a significantly lower intestinal injury score as
      well as lower apoptotic index in jejunum and ileum compared to IR animals.
      CONCLUSIONS: Treatment with simvastatin prevents gut mucosal damage and inhibits
      programmed cell death following intestinal IR in a rat.

PMID- 19855983
TI  - Does intestinal permeability lead to organ failure in experimental necrotizing
      enterocolitis?
AB  - PURPOSE: The rat gavage model is used to explore the pathogenesis and treatment
      of necrotizing enterocolitis (NEC). Although intestinal histological damage is
      seen in this model, intestinal perforation is rarely observed. Whether organ
      failure occurs in this model is largely unknown. We hypothesised that increased
      intestinal permeability leads to organ failure in experimental NEC. METHODS: NEC
      was induced in neonatal rats by gavage feeding of hypertonic formula plus
      exposure to hypoxia plus oral lipopolysaccharide (4 mg/kg per day daily). Breast
      fed rats were used for comparison. At 92 h, lactulose (3 mg) and mannitol (2 mg)
      were administered orally in 0.1 ml water. Four hours later, rats were killed and
      blood samples collected. Lactulose and mannitol were measured by gas
      chromatography-mass spectrometry and lactulose/mannitol ratio calculated as index
      of intestinal permeability. Plasma cardiac troponin-I was measured by ELISA as a
      marker of cardiac damage and plasma creatinine measured spectrophotometrically as
      a marker of renal failure. RESULTS: Experimental NEC induced an increase in
      intestinal permeability (P = 0.0002). This was associated with cardiac damage (P
      < 0.0001), and renal failure (P = 0.004). CONCLUSION: Intestinal permeability is
      increased in experimental NEC in association with increased cardiac damage. Rat
      mortality may be due to cardiac failure secondary to an inflammatory response
      caused by increased intestinal permeability.

PMID- 19855984
TI  - Disturbance of parathyroid hormone-related protein signaling in the nitrofen
      induced hypoplastic lung.
AB  - PURPOSE: Despite remarkable progress in resuscitation and intensive care, the
      morbidity and mortality rates in congenital diaphragmatic hernia (CDH) remain
      high due to severe pulmonary hypoplasia. The pathogenesis of pulmonary hypoplasia
      associated with CDH is still not clearly understood. Pulmonary parathyroid
      hormone-related protein (PTHrP) is expressed in the type II epithelial cells and
      stimulates surfactant production by a paracrine feedback loop regulated by PTHrP
      receptor (PTHrP-R), which is expressed in the mesenchyme, during terminal airway
      differentiation. It has been reported that PTHrP knockout and PTHrP-R null mice
      both exhibit pulmonary hypoplasia, disrupting alveolar maturation before birth.
      We designed this study to test the hypothesis that gene expression of PTHrP and
      PTHrP-R is downregulated in the late stages of lung morphogenesis in the nitrofen
      induced hypoplastic lung. METHODS: Pregnant rats were exposed to either olive oil
      or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, 18,
      and 21 and divided into three groups: control, nitrofen without CDH [CDH(-)], and
      nitrofen with CDH [CDH(+)] (n = 8 at each time point for each group,
      respectively). Total mRNA was extracted from fetal lungs and mRNA expression of
      PTHrP and PTHrP-R was analyzed by real-time RT-PCR and the significant
      differences between the groups were accepted at P < 0.05 by statistical analysis.
      Immunohistochemical studies were also performed to evaluate PTHrP and PTHrP-R
      protein expression at each time point. RESULTS: Pulmonary mRNA expression of
      PTHrP-R was significantly decreased in both nitrofen groups [CDH(-) and CDH(+)]
      compared to controls at D18 and 21. The mRNA level of PTHrP was significantly
      decreased at D21 in both nitrofen groups compared to controls. Immunoreactivity
      of PTHrP and PTHrP-R at D18 and 21 was diminished in the distal epithelium and in
      the mesenchyme, respectively, in the nitrofen-induced hypoplastic lung compared
      to control lungs. There were no significant differences in both gene/protein
      expression of PTHrP and PTHrP-R on D15. CONCLUSION: Downregulation of PTHrP and
      PTHrP-R gene expression during late lung morphogenesis may cause pulmonary
      hypoplasia in the nitrofen CDH model, disrupting alveolar maturation and
      surfactant production by interfering with mesenchymal-epithelial interactions.

PMID- 19855985
TI  - Amniotic fluid stem cell migration after intraperitoneal injection in pup rats:
      implication for therapy.
AB  - PURPOSE: Despite being commonly used in clinical practice, the intraperitoneal
      (i.p.) route has been rarely used for cell delivery. We evaluated the capacity of
      amniotic fluid stem (AFS) cells, administered i.p., to diffuse systemically and
      to integrate into tissues of healthy newborn rats. METHODS: AFS cells were
      obtained from pregnant GFP + Sprague-Dawley rats by c-kit selection. Wild-type
      Sprague-Dawley newborn rats were divided into two groups receiving i.p.: (1) 2 x
      10(6) AFS cells (n = 12); (2) of phosphate buffer saline (PBS) (n = 2) at 24 and
      48 h after birth. Animals were either killed at 96 h of life, and organs
      collected for gfp amplification, or at 3 weeks of life and tissues isolated for
      green fluorescence protein (GFP) immunofluorescence. RESULTS: No adverse effects
      were observed after i.p. injection of PBS or AFS cells. Gfp was amplified in at
      least one organ in all rats injected with AFS cells except one (11/12). The
      intestine was the organ found most frequently positive (67%) followed by liver
      (25%), spleen (16%), heart (16%), lungs (16%), femur (8%) and brain (0%).
      Immunohistochemistry confirmed PCR results. CONCLUSION: In the short term, the
      i.p. administration of AFS cells, is a safe procedure and allows their migration,
      homing and integration into various organs of healthy newborn rats.

PMID- 19855986
TI  - Altered expression of c-kit-positive cells in the ureterovesical junction after
      surgically created vesicoureteral reflux.
AB  - PURPOSE: Peristaltic contractions propel urine unidirectionally from the renal
      pelvis trough the ureter and into the bladder. A morphologically and functionally
      competent ureterovesical junction prevents vesicoureteral reflux (VUR). According
      to current knowledge, pyeloureteral peristalsis is driven by atypical muscle
      cells within the upper urinary tract. Another likely relevant cell population,
      which is c-kit-positive, has been shown to be present within the whole urinary
      tract. Morphological changes of c-kit-positive cells have been described in VUR
      and pyeloureteral junction (PUJ) obstruction. Nevertheless, the functional
      importance of c-kit-positive interstitial cells has not yet been elucidated
      fully. Therefore, we investigated the influence of experimentally created VUR on
      the expression of c-kit-positive cells. MATERIALS AND METHODS: We created left
      sided unilateral VUR in eight Vietnamese pigs using an open surgical technique.
      The VUR was shown to be grade II-III by voiding cystourethrogram (VCUG), 1 and 6
      months after the procedure. The animals were killed after 6 months. The
      vesicoureteral junction and the distal ureters were excised and fixed in 4% PFA.
      Paraffin sections were stained using c-kit immunohistochemistry. A quantitative
      evaluation was performed by two independent investigators. The unaffected,
      contralateral, nonrefluxing ureters served as controls. RESULTS: We identified
      two types of c-kit-immunoreactive cells within the ureterovesical junction and
      distal ureter. The first group was comprised of round-shaped cells with
      substantial intracellular granulas, which resembled mast cells. Mast cells were
      found in the subepithelial region as well as between the muscle bundles. The
      number of mast cells was slightly increased in the VUR group. The second group
      consisted of spindle-shaped, bipolar ICC-like cells, which were seen mainly in
      the submucosal and muscular layers. The number of spindle-shaped c-kit
      immunoreactive cells was markedly decreased in the refluxing ureter compared to
      the controls. CONCLUSIONS: Surgically created VUR leads to altered expression of
      c-kit-positive cells. The altered distribution of c-kit-positive ICC-like cells
      might further contribute to the impairment of coordinated pyeloureteral
      peristalsis.

PMID- 19855987
TI  - Iatrogenic colonic perforation by colonoscopy: a fatal complication for patients
      with a high anesthetic risk.
AB  - PURPOSE: Colonoscopy is currently a standard and widespread technique used in
      screening for colorectal cancer. Iatrogenic colonic perforation during
      colonoscopy is an unfortunate complication that can induce significant morbidity
      and even death. Here, we reviewed the clinical results of iatrogenic colonoscopic
      perforation in our hospital. METHODS: This was a retrospective review of 35,186
      colonoscopies performed in the Tri-Service General Hospital, Taipei, Taiwan from
      January 1998 to December 2007. Patient demographic data, indications,
      comorbidities, operative history, perforation site, time of diagnosis,
      management, complications, hospital stay, and outcomes were recorded. RESULTS: In
      this 10-year period, 23 cases of iatrogenic colonic perforation were recorded
      (0.065%) affecting 11 men and 12 women. The mean age was 71.2 years. There were
      13 patients in American Society of Anesthesiology (ASA) classifications 1 or 2
      (low anesthetic risk, group A), and ten patients in ASA classes 3 or 4 (high
      anesthetic risk, group B). The mean hospital stay was 12 days in group A versus
      23.5 days in group B (P = 0.002). Moreover, four patients in group B died (17%; P
      = 0.024). CONCLUSION: Colonoscopy-related perforation can progress to peritonitis
      and sepsis, resulting in serious morbidity or death. High-anesthetic risk
      patients with colonic perforation have a longer hospital stay and a poor
      prognosis. Hence, patients need to be informed of the complications of
      colonoscopy, and clinicians must be cautioned about the potential problems for
      patients with a high-anesthetic risk when performing the procedure.

PMID- 19855988
TI  - Reduction of radiation dose during radiofrequency denervation of the lumbar facet
      joints using the new targeting system SabreSource: a prospective study in 20
      patients.
AB  - BACKGROUND AND AIMS: Facet joint denervation is a frequently performed technique
      to treat facet joint syndrome. Most often this technique is used under
      fluoroscopic guidance implicating high radiation doses for both patients and
      surgeons. This prospective study was performed to evaluate the effectiveness in
      reducing radiation dose during radiofrequency ablation therapy of the lumbar
      facet joints and to evaluate the feasibility and possibilities of the new real
      time image guidance system SabreSource. MATERIALS AND METHODS: As much as 20
      consecutive patients with radiofrequency ablation therapy of the facet joints L4
      to S1 were included. Ten patients were treated by fluoroscopic control alone; the
      following 10 patients were treated with the SabreSource image guidance system. A
      total of 40 thermal ablations to the facet joints were performed. Each patient
      was given one thermal ablation on both sides of the vertebral segment, either to
      the facet joints of L4-L5 or of L5-S1. Pain, according to the visual analogue
      scale (VAS), was documented before and 6 h after the intervention. Radiation
      dose, time of radiation and the number of shots needed to place the
      radiofrequency cannula were recorded. RESULTS: No complications occurred. Before
      therapy, the mean VAS in all patients was 7.6 (range 6-10). After therapy the
      mean VAS in all patients was 3.4 (range 0-5). Compared to the fluoroscopy-guided
      thermal ablation therapy the SabreSource system significantly reduced the number
      of fluoroscopy exposures (reduction 23.53%, p = 0.02), the time of radiation
      exposure (reduction 21.2%, p = 0.03) and the mean entrance surface dose
      (reduction 30.46%, p = 0.01). CONCLUSION: The SabreSource System reduces
      radiation exposure and radiation dose in the radiofrequency denervation therapy
      of the lumbar facet joints and can be applied for other minimally invasive
      techniques.

PMID- 19855989
TI  - Term and preterm (<34 and <37 weeks gestation) placental pathologies associated
      with fetal growth restriction.
AB  - OBJECTIVE: The present study was aimed to compare term versus preterm placental
      pathologies associated with fetal growth restriction (FGR). STUDY DESIGN: A
      retrospective cohort study was performed, including all singleton deliveries of
      FGR with placental pathology examination. Comparison of placental findings was
      performed between neonates who were born at term versus preterm. Preterm was
      defined as <37 completed weeks of gestation, and <34 weeks gestation in another
      analysis. When one or more of the following pathology was found in microscopic
      examination of the placental tissue, the term uteroplacental insufficiency was
      defined: placental infarct, fibrosis of chorionic villi, thickening of blood
      vessels and poor vascularity of the chorionic villi. RESULTS: Macroscopic
      placental findings were available for 1,104 singleton FGR neonates; of these, 395
      placentas had microscopic examinations. A significant greater proportion of
      preterm FGR cases had pathology findings associated with uteroplacental
      insufficiency as compared to term FGR (29.4 vs. 36.7%; OR = 1.4 95%, CI = 1.05
      1.9; P = 0.019). The same pattern was seen while comparing placentas of FGR
      neonates who were born before and after 34 weeks (32.4 vs. 39.4%; OR = 1.4, 95%
      CI 1.02-1.8; P = 0.028). Syncytial knots were significantly more common in
      placentas from neonates who were delivered before 34 weeks of pregnancy (15.2 vs.
      6.3%; OR = 2.6, 95% CI 1.3-5.6; P = 0.005). This trend was not statistically
      significant while comparing FGR before and after 37 weeks gestation (10.9 vs.
      4.6%; OR = 2.4, 95% CI 0.99-7.7; P = 0.052). Meconial impregnation was more
      common among term versus preterm FGR neonates <37 weeks (22.4% vs. 7.2% OR = 3.7,
      95% CI 2.3-5.9; P < 0.001), as well as among neonates who were born before and
      after 34 weeks of gestation (14.5 vs. 5.9%; OR = 0.4, 95% CI 0.2-0.6; P < 0.001).
      CONCLUSIONS: Placentas of preterm FGR neonates (either <37 weeks or <34 weeks
      gestation) reveal numerous pathologies reflecting uteroplacental insufficiency
      and abnormal blood supply. The presence of increased syncytial knots in preterm
      FGR neonates is probably due to exposure to hypoxia and reactive oxygen agents.

PMID- 19855990
TI  - Congenital hydrocephalus: gestational and neonatal outcomes.
AB  - PURPOSE: To evaluate gestational and neonatal outcomes in pregnancies complicated
      by fetal hydrocephalus. METHODS: Retrospective analysis of 287 cases of fetal
      hydrocephalus followed at the Fetal Medicine Unit of the University of Campinas
      in the period of 1996 to 2006. RESULTS: Mean maternal age was 25 years, mean
      gestational age at diagnosis was 27 weeks. There were 50 cases of isolated
      ventriculomegaly, 95 cases of Chiari II malformation and 142 cases of
      ventriculomegaly associated with other malformations. Preterm delivery and
      vaginal delivery were more frequent in the group of ventriculomegaly associated
      with other malformations. Cardiac, skeletal and renal malformations were the most
      common associated malformations. Cesarean section was common (95%) in the Chiari
      II group. Fetal and neonatal death occurred more frequently (29 and 68%,
      respectively) in the group of ventriculomegaly associated with other
      malformations. Chromosomal anomalies were present in 15% of 165 investigated
      cases. CONCLUSIONS: Fetal and neonatal prognosis and outcome are associated with
      the presence of associated anomalies and aneuploidy.

PMID- 19855991
TI  - Use of CMC foam sinus dressing in FESS.
AB  - Aim is to determine the efficacy and pain level associated with the use of
      dissolvable carboxymethyl cellulose (CMC) foam dressing in functional endoscopic
      sinus surgery (FESS) in adult patients. In the present prospective study, 60
      patients with bilateral chronic rhinosinusitis were included. All patients
      underwent bilateral FESS. Thirty patients had both nasal cavities packed with
      dissolvable CMC foam (CMCF) and another 30 patients had their nasal cavities
      packed with routine nasal packing (RNP) in latex glove fingers. The haemostatic
      effect of the CMCF was assessed during the recovery period, and pain levels were
      recorded by the patients on a visual analogue scale 24 h after surgery. The
      prevalence of postoperative middle meatal synechia formation was assessed 1, 2, 4
      and 8 weeks after the operation. Four (13.3%) of the patients packed with CMCF
      had primary postoperative bleeding during the recovery period and required
      additional dressing. Bleeding appeared in two (6.7%) patients packed with RNP.
      The mean level of pain was 0.962 (range 0-4) for patients packed with CMCF but
      was 5.5 (range 3-9) for patients packed with RNP. Four (6.7%) of 26 CMCF patients
      and 10 (35.7%) of 28 RNP patients developed a synechia in the middle meatus. We
      found that dissolvable CMC foam dressing is associated with very low levels of
      localised pain and with low levels of postoperative bleeding and synechia
      formation.

PMID- 19855992
TI  - An approach to the assessment of risk from chronic radiation to populations of
      European lobster, Homarus gammarus (L.).
AB  - The basic principles underlying a four-discrete age group, logistic, growth model
      for the European lobster Homarus gammarus are presented and discussed at proof-of
      concept level. The model considers reproduction, removal by predation, natural
      death, fishing, radiation and migration. Non-stochastic effects of chronic low
      linear energy transfer (LET) radiation are modelled with emphasis on (99)Tc,
      using three endpoints: repairable radiation damage, impairment of reproductive
      ability and, at higher dose rates, mortality. An allometric approach for the
      calculation of LD(50/30) as a function of the mass of each life stage is used in
      model calibration. The model predicts that at a dose rate of 1 Gy day(-1),
      lobster population reproduction and survival become severely compromised, leading
      eventually to population extinction. At 0.01 Gy day(-1), the survival rate of an
      isolated population is reduced by 10%, mainly through loss of fecundity,
      comparable to natural migration losses. Fishing is the main ecological stress and
      only dose rates in the range 0.03-0.1 Gy day(-1) can achieve discernible effects
      above it. On the balance of radiation and other ecological stresses, a benchmark
      value of 0.01 Gy day(-1) is proposed for the protection of lobster populations.
      This value appears consistent with available information on radiation effects in
      wildlife.

PMID- 19855993
TI  - Radon and risk of death from cancer and cardiovascular diseases in the German
      uranium miners cohort study: follow-up 1946-2003.
AB  - Data from the German uranium miners cohort study were analyzed to investigate the
      radon-related risk of mortality from cancer and cardiovascular diseases. The
      Wismut cohort includes 58,987 men who were employed for at least 6 months from
      1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. By
      the end of 2003, a total of 3,016 lung cancer deaths, 3,355 deaths from
      extrapulmonary cancers, 5,141 deaths from heart diseases and 1,742 deaths from
      cerebrovascular diseases were observed. Although a number of studies have already
      been published on various endpoints in the Wismut cohort, the aim of the present
      analyses is to provide a direct comparison of the magnitude of radon-related risk
      for different cancer sites and cardiovascular diseases using the same data set,
      the same follow-up period and the same statistical methods. A specific focus on a
      group of cancers of the extrathoracic airways is also made here, due to the
      assumed high organ doses from absorbed radon progeny. Internal Poisson regression
      was used to estimate the excess relative risk (ERR) per unit of cumulative
      exposure to radon in working level months (WLM) and its 95% confidence limits
      (CI). There was a statistically significant increase in the risk of lung cancer
      with increasing radon exposure (ERR/WLM = 0.19%; 95% CI: 0.17%; 0.22%). A
      smaller, but also statistically significant excess was found for cancers of the
      extrathoracic airways and trachea (ERR/WLM = 0.062%; 95% CI: 0.002%; 0.121%).
      Most of the remaining nonrespiratory cancer sites showed a positive relationship
      with increasing radon exposure, which, however, did not reach statistical
      significance. No increase in risk was noted for coronary heart diseases (ERR/WLM
      = 0.0003%) and cerebrovascular diseases (ERR/WLM = 0.001%). The present data
      provide clear evidence of an increased radon-related risk of death from lung
      cancer, some evidence for an increased radon-related risk of death from cancers
      of the extrathoracic airways and some other extrapulmonary cancers, and no
      evidence for mortality from cardiovascular diseases. These findings are
      consistent with the results of other miner studies and dosimetric calculations
      for radon-related organ doses.

PMID- 19855994
TI  - Restoration of blood pH between repeated bouts of high-intensity exercise:
      effects of various active-recovery protocols.
AB  - To determine which active-recovery protocol would reduce faster the high blood
      H(+) and lactate concentrations produced by repeated bouts of high-intensity
      exercise (HIE). On three occasions, 11 moderately trained males performed 4 bouts
      (1.5 min) at 163% of their respiratory compensation threshold (RCT) interspersed
      with active-recovery: (1) 4.5 min pedalling at 24% RCT (S(HORT)); (2) 6 min at
      18% RCT (M(EDIUM)); (3) 9 min at 12% RCT (L(ONG)). The total work completed
      during recovery was the same in all three trials. Respiratory gases and
      arterialized-blood samples were obtained during exercise. At the end of exercise,
      L(ONG) in comparison to S(HORT) and M(EDIUM) increased plasma pH (7.32 +/- 0.02
      vs. approximately 7.22 +/- 0.03; P < 0.05), while reduced lactate concentration
      (8.5 +/- 0.9 vs. approximately 10.9 +/- 0.8 mM; P < 0.05). Ventilatory equivalent
      for CO(2) was higher in L(ONG) than S(HORT) and M(EDIUM) (31.4 +/- 0.5 vs.
      approximately 29.6 +/- 0.5; P < 0.05). Low-intensity prolonged recovery between
      repeated bouts of HIE maximized H(+) and lactate removal likely by enhancing
      CO(2) unloading.

PMID- 19855995
TI  - Role of the cAMP-binding protein Epac in cardiovascular physiology and
      pathophysiology.
AB  - Exchange proteins directly activated by cyclic AMP (Epac) were discovered 10
      years ago as new sensors for the second messenger cyclic AMP (cAMP). Epac family,
      including Epac1 and Epac2, are guanine nucleotide exchange factors for the Ras
      like small GTPases Rap1 and Rap2 and function independently of protein kinase A.
      Given the importance of cAMP in the cardiovascular system, numerous molecular and
      cellular studies using specific Epac agonists have analyzed the role and the
      regulation of Epac proteins in cardiovascular physiology and pathophysiology. The
      specific functions of Epac proteins may depend upon their microcellular
      environments as well as their expression and localization. This review discusses
      recent data showing the involvement of Epac in vascular cell migration,
      endothelial permeability, and inflammation through specific signaling pathways.
      In addition, we present evidence that Epac regulates the activity of various
      cellular compartments of the cardiac myocyte and influences calcium handling and
      excitation-contraction coupling. The potential role of Epac in cardiovascular
      disorders such as cardiac hypertrophy and remodeling is also discussed.

PMID- 19855996
TI  - Identification and characterization of two bamboo (Phyllostachys praecox)
      AP1/SQUA-like MADS-box genes during floral transition.
AB  - Bamboo (Bambusoideae) is by far the largest member of the grass family Poaceae,
      which is vital to the economy of many countries in the tropics and subtropics.
      However, the mechanism of flowering of bamboo (Phyllostachys praecox) is still
      unknown. In this study, we isolated two novel genes from P. praecox and evaluated
      their functional characteristics. The sequence and phylogenetic analysis
      indicated that these two genes, named PpMADS1 and PpMADS2, belong to FUL3 and
      FUL1 clade of Poaceae AP1/SQUA-like genes, respectively. The PpMADS2 possesses a
      truncated C terminus lacking the highly conserved paleoAP1 motif. It was further
      confirmed that the truncated C-terminal region was produced by natural sequence
      deletion in exons, but not by alternative splicing. Ectopic expression of PpMADS1
      and PpMADS2 significantly promoted early flowering through upregulation of AP1 in
      Arabidopsis. Yeast two-hybrid experiments demonstrated that AP1 protein can
      interact with PpMADS1 but not PpMADS2, suggesting that these two genes may act
      differently in signaling early flowering of bamboo plants. RT-qPCR and in situ
      hybridization analysis revealed distinct expression patterns of these two genes
      in vegetative and reproductive tissues of bamboo. Taken together, our results
      suggest that both PpMADS1 and PpMADS2 are involved in floral transition, and
      PpMADS2 might play more important roles than PpMADS1 in floral development of
      Phyllostachys praecox.

PMID- 19855997
TI  - Late backward effects in the refractory period paradigm: effects of Task 2
      execution on Task 1 performance.
AB  - The central bottleneck model assumes that in the psychological refractory
      paradigm, Task 1 performance is independent of Task 2 demands. Previous studies,
      however, have reported backward crosstalk effects of motor demands in Task 2 on
      Task 1 performance. These effects have been attributed to interference at the
      central level. The present study aimed to isolate more directly potential
      backward effects at the motor level. Therefore, in three experiments, movement
      distance in Task 2 was manipulated using a guided ballistic movement. The results
      showed that movement distance in Task 2 affected reaction time as well as
      response duration in Task 1. It is argued that the backward effect observed in
      this study is due to response coupling at motor rather than central levels.

PMID- 19855998
TI  - Aberrant expression of p27(Kip1)-interacting cell-cycle regulatory proteins in
      ovarian clear cell carcinomas and their precursors with special consideration of
      two distinct multistage clear cell carcinogenetic pathways.
AB  - We have previously reported that alterations of p27(Kip1)-interacting cell-cycle
      proteins frequently occur during the development of endometriosis-associated
      ovarian clear cell adenocarcinoma (CCA; Yamamoto et al., Histopathology in press,
      20). However, CCA also occurs in association with clear cell adenofibroma (CCAF).
      In this study, the expressions of p27(Kip1)-interacting proteins, i.e.,
      p27(Kip1), Skp2, Cks1, cyclin A, cyclin E, and the Ki-67 labeling index (LI),
      were analyzed in 25 CCAFs (11 benign and 14 borderline) and 15 CCAF-associated
      CCAs, and compared with the expression status of each protein in the 23
      previously studied endometriosis-associated CCAs. Although aberrant expression of
      all p27(Kip1)-interacting proteins was more frequent in the CCAF-associated CCAs
      than in the benign CCAFs, statistical significance was found only for Cks1
      overexpression. The frequencies of p27(Kip1) downregulation and overexpression of
      Skp2 and cyclin A were significantly lower in CCAF-associated than in
      endometriosis-associated CCAs (P < 0.05, respectively). The frequencies of
      p27(Kip1) downregulation and Skp2 overexpression in borderline CCAFs were
      significantly lower than those in atypical endometriosis components in
      endometriosis-associated CCAs (P < 0.05, respectively). Mean Ki-67 LI increased
      significantly through benign (4.9%) to borderline (11.1%) CCAF and to CCAF
      associated CCA (30.6%), but the latter two values were significantly lower than
      those in atypical endometriosis (21.4%) and endometriosis-associated CCA (46.9%;
      P < 0.05, respectively). These data suggest that accumulated alterations of
      p27(Kip1)-interacting proteins may accelerate the development of CCAs regardless
      of their carcinogenetic pathways, but that tumor cells in the CCAF-associated
      pathway appear to show slower cell-cycle progression than those in the
      endometriosis-associated pathway, possibly accounting for the distinct
      clinicopathological features of the two CCA subtypes.

PMID- 19855999
TI  - A trial of minimization of chromosome 7 in Aspergillus oryzae by multiple
      chromosomal deletions.
AB  - We aim to create an Aspergillus oryzae mutant with a highly reduced chromosome,
      but better growth, by eliminating the nonessential regions coding various
      dispensable functions for its better industrial use. In our previous study, we
      successfully determined the outline of essential and nonessential regions by
      constructing a series of large chromosomal deletions in A. oryzae chromosome 7.
      Based on these results, we here constructed two mutants, designated RkuAF7A and
      RkuAF7B, lacking 24.7 and 24% (725 and 705 kb) of wild type chromosome 7,
      respectively, using multiple large-scale chromosomal deletions in a recursive
      pyrG-mediated transformation system. Both showed higher amylase activity in DPY
      liquid medium and faster growth rate on malt agar medium relative to the parent
      strain. The two mutants also displayed soft fluffy hyphal morphology when grown
      in DPY liquid media. In addition, the gene expression profile obtained by DNA
      microarray indicated that although the deletion regions were fewer than 2% of the
      whole genome, the effect on whole gene expression exceeded 20%. Among these, the
      genes involved in secondary metabolism showed a relatively large change in their
      gene expression levels. Together, the constructed mutants showing better growth
      and potential usefulness is possibly suitable for further industrial use.

PMID- 19856000
TI  - Imaging in the evaluation of renovascular disease.
AB  - Renovascular disease (RVD) is an important cause of hypertension in children, as
      it often is amenable to potentially curative treatment. Imaging aimed at finding
      RVD therefore needs to have high sensitivity so as not to miss important
      findings. Digital subtraction angiography is the gold standard investigation.
      Doppler ultrasonography, computed tomography (CT) angiography and magnetic
      resonance (MR) angiography can all be helpful, but none has, at present, high
      enough sensitivity to rule out RVD in a child with a suggestion of that
      diagnosis.

PMID- 19856001
TI  - Diagnostic accuracy of postnatal ultrasound screening for urinary tract
      abnormalities.
AB  - The study was aimed at (1) the determination of the incidence of abnormalities of
      the urinary tract in newborn infants detected by postnatal ultrasound screening,
      and (2) the evaluation of the diagnostic accuracy of postnatal ultrasound
      screening for detecting surgical urinary tract abnormalities. The prospective
      study was of full-term neonates born in the University Hospital of Olomouc in
      2005-2008 who underwent renal ultrasound screening after 72 h of life.
      Significant findings were recorded. Subsequent diagnostic and therapeutic
      procedures were recorded and evaluated in a group of children with detected renal
      pelvic dilatation (RPD). (1) A total of 6,088 newborn infants was examined. The
      absolute and relative RPD incidence rates (anteroposterior diameter, APD) were as
      follows: 5-7 mm, 146 (2.4%); 7-10 mm, 70 (1.15%); 10-15 mm, 13 (0.21%), and 15 mm
      or more, 5 (0.08%). Of those, 16 children were operated on for abnormalities of
      the urinary tract, of which nine (56%) had been detected by prenatal screening.
      Other findings: six cases of unilateral renal agenesis, four cases of multicystic
      renal dysplasia, four of renal dystopia, one of polycystic kidney disease and one
      of renal hypoplasia. (2) A group of 224 children with postnatally detected RPD
      was examined, of whom 40 (17.9%) underwent voiding cystourethrography and/or
      scintigraphy and 16 (7.1%) were treated surgically. The receiver operating
      characteristic curves were analyzed, and the areas under the curves were
      calculated. Postnatal renal ultrasound screening is probably a suitable test for
      detecting significant urinary tract abnormalities.

PMID- 19856003
TI  - Apparent viscosity and particle pressure of a concentrated suspension of non
      Brownian hard spheres near the jamming transition.
AB  - We consider the steady shear flow of a homogeneous and dense assembly of hard
      spheres suspended in a Newtonian viscous fluid. In a first part, a mean-field
      approach based on geometric arguments is used to determine the viscous
      dissipation in a dense isotropic suspension of smooth hard spheres and the
      hydrodynamic contribution to the suspension viscosity. In a second part, we
      consider the coexistence of transient solid clusters coupled to regions with free
      flowing particles near the jamming transition. The fraction of particles in
      transient clusters is derived through the Landau-Ginzburg concepts for first
      order phase transition with an order parameter corresponding to the proportion of
      "solid" contacts. A state equation for the fraction of particle-accessible volume
      is introduced to derive the average normal stresses and a constitutive law that
      relates the total shear stress to the shear rate. The analytical expression of
      the average normal stresses well accounts for numerical or experimental
      evaluation of the particle pressure and non-equilibrium osmotic pressure in a
      dense sheared suspension. Both the friction level between particles and the
      suspension dilatancy are shown to determine the singularity of the apparent shear
      viscosity and the flow stability near the jamming transition. The model further
      predicts a Newtonian behavior for a concentrated suspension of neutrally buoyant
      particles and no shear thinning behavior in relation with the shear liquefaction
      of transient solid clusters.

PMID- 19856002
TI  - Severe atypical HUS caused by CFH S1191L--case presentation and review of
      treatment options.
AB  - Atypical hemolytic uremic syndrome (aHUS) has been associated with defective
      regulation of the alternative complement pathway. Although the use of plasma
      therapy is recommended, there is little consensus on the optimal treatment
      regimen. The outcome in many cases remains poor despite an improvement in our
      understanding of the pathology of aHUS. We have followed a female patient with
      aHUS associated with heterozygous complement Factor H (CFH) mutation (S1191L)
      over a period of 15 years. She has been plasma dependent since infancy and has
      subsequently progressed to end stage kidney disease (ESKD) requiring dialysis
      treatment. Despite ESKD she still depends on regular plasma infusions to prevent
      thrombocytopenia. The long-term treatment plan for this patient is challenging.
      Renal transplantation in patients with the S1191L mutation of the CFH gene
      carries a high risk of failure due to recurrence of aHUS in the renal graft.
      Thus, the only available curative treatment seems to be combined liver-kidney
      transplantation, covered by intensive plasma therapy, which comes with a high
      risk of morbidity and mortality. Antibodies against key activating components of
      the complement cascade may provide a promising alternative therapeutic strategy
      in the future. Eculizumab, a monoclonal humanized anti-C5 antibody, has recently
      been shown to be effective and well-tolerated in patients with paroxysmal
      nocturnal hemoglobinuria by preventing complement-mediated lysis of affected
      erythrocytes. Treatment of our patient with eculizumab is supported by recent
      reports on its successful use in two (pediatric and adult) patients with
      complement-based aHUS.

PMID- 19856004
TI  - The first-passage problem for diffusion through a cylindrical pore with sticky
      walls.
AB  - We calculate the first-passage time distribution for diffusion through a
      cylindrical pore with sticky walls. A particle diffusively explores the interior
      of the pore through a series of binding and unbinding events with the cylinder
      wall. Through a diagrammatic expansion we obtain first-passage time statistics
      for the particle's exit from the pore. Connections between the model and
      nucleocytoplasmic transport in cells are discussed.

PMID- 19856005
TI  - On a moving liquid film and its instability on textured surfaces.
AB  - Recently, two regimes of viscous friction on textured surfaces were proposed in
      the context of penetration of liquid film into the texture (EPL 79, 56005
      (2007)): the Poiseuille and Stokes regimes. With this idea on viscous friction,
      we theoretically discuss instabilities on a liquid film on textured surfaces when
      the film is forced to move with external forces. When a film recedes due to a
      pressure drop, we find scaling laws for instabilities to be checked in future
      experiments. When a circular film expands due to centrifugal force we find that
      the expanding film is stable against rim fluctuations (within the linear
      stability analysis) with its radius determined by a simple equation. Our
      discussion sheds light on the curvature of the front of the moving liquid film on
      textured surfaces and how the film thickness is kept fixed to the texture height
      on textured surfaces, aspects which have not been discussed in previous studies.

PMID- 19856006
TI  - The challenge of corporatisation: the experience of Portuguese public hospitals.
AB  - The inability of traditional state organisations to respond to new economic,
      technological and social challenges and the associated emerging problems has made
      it necessary to adopt new methods of health management. As a result, new
      directions have emerged in the reform of Public Administration together with the
      introduction of innovative models. The aim is to achieve a type of management
      that focuses on results as well as on effort and efficiency. We intend to analyse
      to what extent the adoption of business management models by hospital healthcare
      units can improve their performance, mainly in terms of standards of efficiency.
      Data envelopment analysis (DEA) was used to investigate the efficiency of a set
      of public Portuguese hospitals. The aim was to evaluate the impact of business
      management in Portuguese public hospitals with regards to efficiency,
      specifically taking into account the fact that lack of resources and increased
      health care needs are a present and future reality. From a total of 83 public
      hospitals, a sample of 59 hospitals was chosen, of which 21 are state-owned
      hospital enterprises (SA) and 38 are traditional public administration sector
      hospitals (SPA). This study evaluates hospital performance by calculating two
      efficiency measures associated with two categories of inputs. The first
      efficiency measures the costs associated with hospital production lines and the
      number of beds (representing fixed capacity) as inputs. The annual costs
      generated by the hospitals in the consumption of capital and work (direct and
      indirect costs) are used. A second measure of efficiency is calculated
      separately. This measure includes in the inputs the number of beds as well as the
      human resources available (number of doctors, number of nurses and other
      personnel) in each hospital. With regard to output, the variables that best
      reflect the hospital services rendered were considered: number of inpatient days,
      patients discharged, outpatient visits, emergencies services, sessions in
      hospital day care services and the number of surgeries. The results seem to
      suggest that the introduction of market processes and changes in organisational
      structure--such as managerial autonomy and corporatisation of public hospitals-
      have had a positive impact on Portuguese public hospitals. This positive
      evolution was particularly evident in SA hospitals, but further studies are
      needed to confirm these preliminary results.

PMID- 19856007
TI  - Assessment of depth perception using psychophysical thresholds and
      stereoscopically evoked brain activity.
AB  - Dynamic random-dot stereograms (dRDS) elicit brain activity generated exclusively
      by cortical neurons sensitive to binocular horizontal disparity. We studied 20
      adults with stereovision deficiency but otherwise normal vision. Psychophysical
      thresholds were determined with static RDS and with the three-rod experiment. VEP
      was recorded from seven occipital channels. Stimuli were presented on a monitor
      by dRDS as stereoscopic checkerboard patterns that moved in depth with 8 depth
      reversals per second. Horizontal disparity ranged from 7 to 24.5 min of arc.
      Stimuli were displayed at the center, or in the left or right half field. We
      determined electrophysiological thresholds as well as the disparity where largest
      responses occurred. Subjective and electrophysiological thresholds showed a
      significant positive correlation. In addition, the right visual field was more
      sensitive to dRDS stimuli than other locations. Squint angle was related to the
      disparity thresholds. Our data illustrate correlations between clinical symptoms,
      perceptual deficiency, and VEP parameters.

PMID- 19856008
TI  - Analysis of phospholipids in rat brain using liquid chromatography-mass
      spectrometry.
AB  - The brain is a lipid-rich organ containing complex polar lipids including
      phospholipids (PLs) and sphingolipids. These lipids are involved in the structure
      and function of cell membranes in the brain. We developed a fast and efficient
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify five
      different classes of PLs [Choline glycerophospholipid (consists of phosphatidyl
      choline and plasmenyl choline in these samples), ethanolamine glycerophospholipid
      (consist of phosphatidyl ethanolamine and plasmenyl ethanolamine in these
      samples), phosphatidyl serine, phosphatidyl inositol, and sphingomyelin] in the
      brain tissues of 80-day-old Wistar rats. The PLs were extracted from rat brain
      using chloroform/methanol/water. After separation using a hydrophilic high
      performance liquid chromatography column, PL-class-specific fragmentation (head
      group identification) with a tandem mass spectrometer in positive ion mode was
      utilized to measure changes in the relative concentration of the five PL classes.
      The advantage of this approach was its improved specificity over previously
      reported LC-MS methods. The method had good repeatability (coefficient of
      variation 3-9%, excluding phosphatidyl inositol) and recovery (92-103%) and
      compared well with more laborious traditional methods.

PMID- 19856009
TI  - Quantitative determination of geranyl diphosphate levels in cultured human cells.
AB  - Geranyl diphosphate (GPP), a 10-carbon isoprenoid, is a key intermediate in the
      isoprenoid biosynthetic pathway. This pathway, in addition to leading to sterol
      synthesis, results in the synthesis of farnesyl diphosphate (FPP) and
      geranylgeranyl diphosphate (GGPP), which serve as substrates for protein
      isoprenylation reactions. Basal levels of GPP in mammalian cells previously have
      been undetectable. Here we present a novel, sensitive, nonradioactive method
      which allows for measurement of GPP in mammalian cells. This methodology involves
      extraction of isoprenoids from cultured cells followed by enzymatic conjugation
      of GPP to a fluorescent dansylated-peptide via farnesyl transferase and
      quantification with high-performance liquid chromatography (HPLC). The lower
      limit of detection of GPP is 5 pg, or 0.015 pmol. Basal levels of GPP were
      determined in three human multiple myeloma cell lines (RPMI-8226, U266, H929).
      Treatment of cells with inhibitors of the isoprenoid biosynthetic pathway results
      in marked changes in GPP levels: the HMG-CoA reductase inhibitor lovastatin
      decreases GPP levels by over 50%, while the FPP synthase inhibitor zoledronic
      acid increases GPP levels 16- to 107-fold. This method also allows for the
      simultaneous measurement of GPP, FPP, and GGPP, thus leading to improved
      understanding of the pathway in a multitude of biological systems. Furthermore,
      as drugs targeting this pathway are developed, their biological activity can be
      more directly linked to effects on isoprenoid levels.

PMID- 19856010
TI  - [Meibomian glands. Part I: anatomy, embryology and histology of the Meibomian
      glands].
AB  - The Meibomian glands are large sebaceous glands that are located as separate
      gland strands in parallel arrangement within the tarsal plates of the eyelids.
      Their oily product (meibum) is secreted by a holocrine mechanism during which the
      secretory cells (meibocytes) are completely transformed into the meibum after
      synthesis and accumulation of lipids. After production in the gland acini, meibum
      is transported through the ductal system via the connecting duct (ductule) and
      the central duct towards the orifice at the free lid margin close to the inner
      lid border. The embryological development of the Meibomian glands takes place
      during the differentiation of the eyelids in the sealing phase of the eyelids.
      They are not directly associated with hair follicles but share important
      similarities in embryology, structure and keratinization potency with the cilia.
      Similar to the sebaceous glands Meibomian glands are regulated via sex hormones
      and androgens have a supporting function whereas estrogens act antagonistically.
      However, in contrast to other sebaceous glands they also have a distinct
      innervation, apart from sympathetic and sensory primarily by parasympathetic
      fibers that share the innervation pattern of the lacrimal glands. The anatomy,
      embryology and histology of the Meibomian glands are explained here, mainly with
      respect to humans, in an extensive review.

PMID- 19856011
TI  - [Meibomian glands. Part II: physiology, characteristics, distribution and
      function of meibomian oil].
AB  - The oily secretion (meibum) of the Meibomian glands forms the superficial layer
      of the pre-ocular tear film and reduces evaporation of the aqueous phase. Meibum
      is a complex mixture of various lipids and minor protein components as well as
      other components of the secretory meibocytes, which form a clear liquid at body
      temperature. The exact composition and functions of meibum are still partly
      unknown, in particular the interaction of the water insoluble non-polar lipids
      with the polar, partly water soluble, lipids and potentially with proteins, which
      altogether interact to maintain the connection with the underlying aqueous tear
      phase. Meibum is transported within the gland by the force of secretory pressure
      from continuous secretion and by muscular action of the orbicularis muscle and
      Riolans muscles during blinking. After delivery of meibum onto the posterior lid
      margin the oil moves from the posterior lid margin reservoir onto the tear
      meniscus and is pulled as a thin layer onto the pre-ocular tear film every time
      the lid opens. During lid closure it is compressed and a small part is
      continuously renewed. Meibum also has a barrier function against the spillage of
      tears over the inner border of the lid and against the entry of skin lipids
      (sebum) from the free lid margin.

PMID- 19856020
TI  - Percutaneous electrothrombosis: a minimally invasive technique for the treatment
      of deep hemangiomas.
AB  - BACKGROUND: A percutaneous electrocauterization technique for the treatment of
      deep hemangiomas is introduced as an alternative and minimally invasive treatment
      mode. METHODS: Percutaneous electrothrombosis was applied through a needle
      catheter that is a small silicone catheter with a needle guide in it. Thus, it is
      possible to do needle-point monopolar electrocauterization only at the needle tip
      because of the insulation of the other parts of the needle by the silicone
      catheter. By retracting the needle with catheter on it during
      electrocauterization, electrothrombosis was achieved through and around the
      channel of the needle, leaving vascularized tissue areas between the channels to
      perfuse the skin or mucosa covering the hemangioma. RESULTS: This technique was
      applied as a single treatment or before surgery for the treatment of cavernous
      hemangiomas to more than 40 patients. However, adequate documentation was found
      for only 10 patients. After percutaneous electrocauterization of deep
      hemangiomas, discrete areas of skin necrosis appeared in some patients during the
      healing period, but the subsequent debridement and surgical excisions were easier
      because of the thrombosis effect of the technique due to the diffuse denaturation
      and fibrosis through and around the electrocauterization channels. The follow-up
      period was 1-13 years. CONCLUSION: The proposed percutaneous electrocauterization
      technique for the treatment of deep hemangiomas achieved four effects: (1) volume
      reduction, (2) bleeding reduction, (3) anesthesia time reduction, and (4) cost
      reduction. The technique can be defined as a minimally invasive and effective
      alternative treatment for deep hemangiomas.

PMID- 19856012
TI  - Gene expression of NMDA receptor subunits in the cerebellum of elderly patients
      with schizophrenia.
AB  - To determine if NMDA receptor alterations are present in the cerebellum in
      schizophrenia, we measured NMDA receptor binding and gene expression of the NMDA
      receptor subunits in a post-mortem study of elderly patients with schizophrenia
      and non-affected subjects. Furthermore, we assessed influence of genetic
      variation in the candidate gene neuregulin-1 (NRG1) on the expression of the NMDA
      receptor in an exploratory study. Post-mortem samples from the cerebellar cortex
      of ten schizophrenic patients were compared with nine normal subjects. We
      investigated NMDA receptor binding by receptor autoradiography and gene
      expression of the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D by in
      situ hybridization. For the genetic study, we genotyped the NRG1 polymorphism
      rs35753505 (SNP8NRG221533). Additionally, we treated rats with the antipsychotics
      haloperidol or clozapine and assessed cerebellar NMDA receptor binding and gene
      expression of subunits to examine the effects of antipsychotic treatment. Gene
      expression of the NR2D subunit was increased in the right cerebellum of
      schizophrenic patients compared to controls. Individuals carrying at least one C
      allele of rs35753505 (SNP8NRG221533) showed decreased expression of the NR2C
      subunit in the right cerebellum, compared to individuals homozygous for the T
      allele. Correlation with medication parameters and the animal model revealed no
      treatment effects. In conclusion, increased NR2D expression results in a
      hyperexcitable NMDA receptor suggesting an adaptive effect due to receptor
      hypofunction. The decreased NR2C expression in NRG1 risk variant may cause a
      deficit in NMDA receptor function. This supports the hypothesis of an abnormal
      glutamatergic neurotransmission in the right cerebellum in the pathophysiology of
      schizophrenia.

PMID- 19856021
TI  - Achieving conservation goals in managed forests of the southeastern coastal
      plain.
AB  - Managed forests are a primary land use within the Coastal Plain of the southern
      United States. These forests are generally managed under standards, guidelines,
      or regulations to conserve ecosystem functions and services. Economic value of
      commercial forests provides incentives for landowners to maintain forests rather
      than convert them to other uses that have substantially reduced environmental
      benefits. In this review, we describe the historical context of commercial forest
      management in the southern United States Coastal Plain, describe how working
      forests are managed today, and examine relationships between commercial forest
      management and maintenance of functional aquatic and wetland systems and
      conservation of biological diversity. Significant challenges for the region
      include increasing human population and urbanization and concomitant changes in
      forest area and structure, invasive species, and increased interest in forest
      biomass as an energy feedstock. Research needs include better information about
      management of rare species and communities and quantification of relationships
      between ecosystem attributes and forest management, including biomass production
      and harvest. Incentives and better information may help commercial forest
      managers in the Coastal Plain more efficiently contribute to landscape-scale
      conservation goals.

PMID- 19856022
TI  - Assessing landscape functions with broad-scale environmental data: insights
      gained from a prototype development for Europe.
AB  - We examine the advantages and disadvantages of a methodological framework
      designed to analyze the poorly understood relationships between the ecosystem
      properties of large portions of land, and their capacities (stocks) to provide
      goods and services (flows). These capacities (stocks) are referred to as
      landscape functions. The core of our assessment is a set of expert- and
      literature-driven binary links, expressing whether specific land uses or other
      environmental properties have a supportive or neutral role for given landscape
      functions. The binary links were applied to the environmental properties of 581
      administrative units of Europe with widely differing environmental conditions and
      this resulted in a spatially explicit landscape function assessment. To check
      under what circumstances the binary links are able to replace complex
      interrelations, we compared the landscape function maps with independently
      generated continent-wide assessments (maps of ecosystem services or environmental
      parameters/indicators). This rigorous testing revealed that for 9 out of 15
      functions the straightforward binary links work satisfactorily and generate
      plausible geographical patterns. This conclusion holds primarily for production
      functions. The sensitivity of the nine landscape functions to changes in land use
      was assessed with four land use scenarios (IPCC SRES). It was found that most
      European regions maintain their capacity to provide the selected services under
      any of the four scenarios, although in some cases at other locations within the
      region. At the proposed continental scale, the selected input parameters are thus
      valid proxies which can be used to assess the mid-term potential of landscapes to
      provide goods and services.

PMID- 19856024
TI  - Computer-assisted assessment of hyoid bone motion from videofluoroscopic swallow
      studies.
AB  - Videofluoroscopic examination of swallowing remains the standard for evaluation
      of patients with swallowing complaints. Although attempts have been made to
      objectify aspects of the study, findings from the study are largely subjective
      and reliant on clinician training and judgment leading to considerable inter
      rater variability. We describe a computerized image analysis program designed to
      objectify one component of the swallow study, the movement of the hyoid bone.
      Hyoid motion has been shown to be different in dysphagic versus non-dysphagic
      patients. Reduced hyoid elevation is also considered a risk factor for
      aspiration; however, there has not been much work done on actually quantifying
      hyoid motion and associating it with other aspects of the swallow study. The
      clinician is prompted to define the hyoid bone in a calibration frame, and the
      system then tracks that region of interest throughout the rest of the study. This
      system shows strong correlations with manual analysis and can account for head
      position changes during the study. While the hyoid bone was reported on in this
      study, other regions of interest within the image field could also be tracked
      using this technique. A more quantitative analysis such as this has the
      opportunity to improve the inter-rater reliability of the test and therefore lead
      to more consistent findings from swallow studies.

PMID- 19856025
TI  - Sensory transcutaneous electrical stimulation improves post-stroke dysphagic
      patients.
AB  - Oropharyngeal dysphagia is frequent in stroke patients and increases mortality,
      mainly because of pulmonary complications. We hypothesized that sensitive
      transcutaneous electrical stimulation applied submentally during swallowing could
      help rehabilitate post-stroke oropharyngeal dysphagia by improving cortical
      sensory motor circuits. Eleven patients were recruited for the study (5 females,
      68 +/- 11 years). They all suffered from recent oropharyngeal dysphagia (>eight
      weeks) induced by a hemispheric (n = 7) or brainstem (n = 4) stroke, with
      pharyngeal residue and/or laryngeal aspiration diagnosed by videofluoroscopy.
      Submental electrical stimulations were performed for 1 h every day for 5 days
      (electrical trains: 5 s every minute, 80 Hz, under motor threshold). During the
      electrical stimulations, the patients were asked to swallow one teaspoon of paste
      or liquid. Swallowing was evaluated before and after the week of stimulations
      using a dysphagia handicap index questionnaire, videofluoroscopy, and cortical
      mapping of pharyngeal muscles. The results of the questionnaire showed that
      oropharyngeal dysphagia symptoms had improved (p < 0.05), while the
      videofluoroscopy measurements showed that laryngeal aspiration (p < 0.05) and
      pharyngeal residue (p < 0.05) had decreased and that swallowing reaction time (p
      < 0.05) had improved. In addition, oropharyngeal transit time, pharyngeal transit
      time, laryngeal closure duration, and cortical pharyngeal muscle mapping after
      the task had not changed. These results indicated that sensitive submental
      electrical stimulations during swallowing tasks could help to rehabilitate post
      stroke swallowing dysphagia by improving swallowing coordination. Plasticity of
      the sensory swallowing cortex is suspected.

PMID- 19856026
TI  - Fluoroscopic surrogate for pharyngeal strength: the pharyngeal constriction ratio
      (PCR).
AB  - The pharyngeal constriction ratio (PCR), derived directly from videofluoroscopy
      without the need for manometry, requires validation as a surrogate for pharyngeal
      strength. A correlation of -0.70 was previously identified between PCR and
      pharyngeal clearing pressures (PP) on separate fluoroscopic and manometric
      studies. As PP increases, PCR decreases. The objective of the current study was
      to evaluate the correlation between PCR and PP in 25 patients undergoing
      simultaneous fluoroscopy and pharyngeal manometry. The effect of the manometric
      catheter on PCR was also investigated. The correlation between the PCR and
      averaged pharyngeal clearing pressures was -0.72 (p<0.001). All patients with a
      PCR>0.25 had a P <60 mmHg. PCR did not differ significantly as a consequence of
      the manometric catheter. Results suggest the utility of an objective fluoroscopic
      measure in assessing pharyngeal strength when manometry may not be available or
      possible.

PMID- 19856027
TI  - The Mayo Dysphagia Questionnaire-30: documentation of reliability and validity of
      a tool for interventional trials in adults with esophageal disease.
AB  - The aim of this study was to develop the Mayo Dysphagia Questionnaire-30 Day (MDQ
      30), a tool to measure esophageal dysphagia, by adapting items from validated
      instruments for use in clinical trials, and assess its feasibility,
      reproducibility, and concurrent validity. Outpatients referred to endoscopy for
      dysphagia or seen in a specialty clinic were recruited. Feasibility testing was
      done to identify problematic items. Reproducibility was measured by test-retest
      format. Concurrent validity reflects agreement between information gathered in a
      structured interview versus the patients' written responses. The MDQ-30, a 28
      item instrument, took 10 min (range = 5-30 min) to complete. Four hundred thirty
      one outpatients [210 (49%) men; mean age = 61 years] participated. Overall, most
      concurrent validity kappa values for dysphagia were very good to excellent with a
      median of 0.78 (min 0.28, max 0.95). The majority of reproducibility kappa values
      for dysphagia were moderate to excellent with a median kappa value of 0.66 (min
      0.07, max 1.0). Overall, concurrent validity and reproducibility kappa values for
      gastroesophageal reflux disease (GERD) symptoms were 0.81 (95% CI = 0.72, 0.91)
      and 0.66 (95% CI = 0.55, 0.77), respectively. Individual item percent agreement
      was generally very good to excellent. Internal consistency was excellent. We
      conclude that the MDQ-30 is an easy-to-complete tool to evaluate reliably
      dysphagia symptoms over the last 30 days.

PMID- 19856028
TI  - Systematic review of randomized and nonrandomized trials of the clinical response
      and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver
      metastases.
AB  - BACKGROUND: Neoadjuvant chemotherapy prior to hepatectomy in patients with
      resectable colorectal liver metastases (CLM) may facilitate the resectability of
      the liver lesions and treat occult metastasis but may also lead to hepatic
      parenchyma damage. There is argument over the oncologic benefit of this practice
      in patients who would already be suitable for a curative hepatectomy. METHODS:
      Extensive literature search of databases (MEDLINE and PubMed) to identify
      published studies of preoperative systemic chemotherapy for resectable CLM was
      undertaken with clinical response to treatment and survival outcomes as the
      endpoints. RESULTS: Twenty-three studies were reviewed: 1 phase III randomized
      control trial, 3 phase II studies, and 19 observational studies, comprising 3,278
      patients. Objective (complete/partial) radiological response was observed in 64%
      (range 44-100%) [complete 4% (range 0-38%), partial 52% (range 10-90%)] of
      patients after neoadjuvant chemotherapy. Pathologically, a median of 9% (range 2
      24%) and 36% (range 20-60%) had complete and partial response, respectively. Of
      patients, 41% (range 0-65%) had stable or progressive disease whilst on
      neoadjuvant chemotherapy. Median disease-free survival (DFS) was 21 (range 11-40)
      months. Median overall survival (OS) was 46 (range 20-67) months. CONCLUSION:
      Current evidence suggests that objective response to neoadjuvant chemotherapy may
      be achieved with improvement in DFS in patients with resectable CLM. A
      prospective randomized trial of neoadjuvant therapy versus adjuvant therapy after
      liver resection is required to determine the optimal perisurgical treatment
      regimen.

PMID- 19856029
TI  - A systematic review of resectability and survival after concurrent chemoradiation
      in primarily unresectable pancreatic cancer.
AB  - PURPOSE: The objective of this study was to determine the effect on resection
      rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable
      locally advanced pancreatic carcinoma. METHODS: A systematic review of recently
      published literature was performed. Resection rates and survival data were
      derived from reports published from 2000 onwards. Only recent studies, based on
      radiotherapy with standard dose and fractionation, have been analyzed. RESULTS:
      Thirteen studies with a total of 510 patients met selection criteria. A resection
      rate of 8.3-64.2% was reported (median, 26.5%). Of the operated patients, 57.1
      100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional
      pathological complete responses (CR, 3.0-8.8%). When outcome in all patients was
      considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing
      favorably with literature data based on concurrent chemoradiation alone (range,
      8.6-13 months). Surprisingly, in patients with unresectable tumor at
      presentation, median survival after surgery ranged from 16.4 to 32.3 (median,
      23.6) months. CONCLUSIONS: The finding of a high proportion of R0 resection among
      all resections performed confirms the activity of neoadjuvant radiochemotherapy
      and should not be neglected. Based on these data, patients with unresectable
      pancreatic cancer without disease progression after chemoradiotherapy should be
      considered for radical surgery.

PMID- 19856030
TI  - Lymph node metastases in diffuse malignant peritoneal mesothelioma.
AB  - BACKGROUND: Improved survival has been reported for diffuse malignant peritoneal
      mesothelioma (DMPM) treated by surgical cytoreduction and hyperthermic
      intraperitoneal chemotherapy (HIPEC). The significance of lymph node involvement
      in this disease is still poorly understood. METHODS: Prospectively collected
      clinical data on 83 consecutive patients with DMPM undergoing surgical
      cytoreduction and closed-abdomen HIPEC with cisplatin and doxorubicin were
      reviewed. Clinically suspicious lymph nodes were submitted to pathological
      examination. The impact of nodal involvement on survival was assessed by
      multivariate analysis; 14 clinicopathological control variables were tested.
      RESULTS: For the overall series, median follow-up was 52 months (range 1-126
      months) and 5-year overall survival (OS) was 49.5%. Lymph nodes were submitted to
      pathological examination in 38 patients, being positive in 11 and negative in 27.
      Lymph nodes were not clinically suspicious and not sampled in 45 patients. Iliac
      (n = 7) and paracolic (n = 2) nodes were the most commonly involved nodes. OS was
      18.0% for patients with pathologically positive nodes and 82.5% for those with
      pathologically negative nodes (P = 0.0024). On multivariate analysis,
      pathologically negative (versus positive/not assessed) nodes [hazard ratio (HR) =
      2.81; 95% confidence interval (CI) = 1.12-7.05; P = 0.027], epithelial subtype
      (HR = 2.93; CI = 1.24-6.95; P = 0.015), mitotic count <or=5/50 high-power
      microscopic fields (HPF) (HR = 5.34; CI = 1.96-14.54; P = 0.001), and
      completeness of cytoreduction (HR = 2.06; CI = 1.19-3.56; P = 0.001) correlated
      with increased OS. Positive nodes (versus negative/not assessed) did not
      significantly correlate with survival. CONCLUSION: Pathologically negative nodes
      (as compared with pathological positive and not assessed), along with
      pathological and biological features, independently correlated with increased
      survival following comprehensive treatment. This suggests the need for careful
      node sampling when performing surgical cytoreduction for DMPM patients.

PMID- 19856031
TI  - The era of robotic surgery for colorectal cancer.

PMID- 19856032
TI  - A structured threshold model for mountain pine beetle outbreak.
AB  - A vigor-structured model for mountain pine beetle outbreak dynamics within a
      forest stand is proposed and analyzed. This model explicitly tracks the changing
      vigor structure in the stand. All model parameters, other than beetle vigor
      preference, were determined by fitting model components to empirical data. An
      abrupt threshold for tree mortality to beetle densities allows for model
      simplification. Based on initial beetle density, model outcomes vary from
      decimation of the entire stand in a single year, to inability of the beetles to
      infect any trees. An intermediate outcome involves an initial infestation which
      subsequently dies out before the entire stand is killed. A model extension is
      proposed for dynamics of beetle aggregation. This involves a stochastic
      formulation.

PMID- 19856033
TI  - Beyond epithelial to mesenchymal transition: a novel role for the transcription
      factor Snail in inflammation and wound healing.
AB  - INTRODUCTION: Snail, a transcription factor linked to epithelial to mesenchymal
      transition (EMT) during embryonic development and tumor progression, is
      associated with migration of cells. During inflammation and tissue injury, cell
      movement is also observed to provide the first line of defense against bacteria
      and to promote wound healing. Therefore, we studied the function of Snail in
      activated macrophages in a variety of inflammatory processes. MATERIALS AND
      METHODS: In this study, we examined the expression and localization of Snail
      during inflammation and tissue injury in rats and human tissue specimens, by
      immunohistochemistry, Western blot, and real-time PCR. We investigated Snail
      expression after stimulation of macrophages with TGF-beta1, LPS, Interleukin-8,
      and MMP-3 in vitro. To further understand the role of Snail in activated
      macrophages, we used Stealth siRNA against Snail, transfected the human
      macrophage cell line THP-1, and measured migration of cells in an in vitro
      invasion assay. RESULTS AND DISCUSSION: We found a strong, transient, and time
      dependent activation of Snail in migrating macrophages at the sites of injury in
      vivo and in vitro, as well as in patients with inflammatory bowel disease.
      Furthermore, we showed that induction of Snail in macrophages is dependent on TGF
      beta1 signaling pathway. Downregulation of Snail by Stealth siRNA led to impaired
      migration of THP-1 cells in an invasion assay after stimulation with TGF-beta1.
      CONCLUSION: We conclude that TGF-beta1 induced migration of activated macrophages
      during inflammation and wound healing is mediated by snail. These results give
      insights in a novel EMT-like mechanism present in immune cell movement during
      tissue injury.

PMID- 19856034
TI  - Achalasia--if surgical treatment fails: analysis of remedial surgery.
AB  - INTRODUCTION: Heller myotomy leads to good-excellent long-term results in 90% of
      patients with achalasia and thereby has evolved to the "first-line" therapy.
      Failure of surgical treatment, however, remains an urgent problem which has been
      discussed controversially recently. MATERIALS AND METHODS: A systematic review of
      the literature was performed to analyze the long-term results of failures after
      Heller's operation with emphasis on treatment by remedial myotomy. DISCUSSION:
      Other reinterventions and their causes after failure of surgical treatment in
      patients with achalasia are discussed.

PMID- 19856035
TI  - Circular- vs. linear-stapled gastrojejunostomy in laparoscopic Roux-en-Y gastric
      bypass.
AB  - BACKGROUND: Different surgical techniques have been developed for the
      gastrojejunostomy (GJS) in laparoscopic Roux-en-Y gastric bypass (LRYGBP) with
      the anastomosis performed in a circular-stapled, linear-stapled, or totally hand
      sewn way. No technique seems superior to the other as no consistent data on
      weight loss or complication rates were described. METHODS: A matched-pair study
      was conducted including a total of 150 patients, who underwent primary
      antegastric, antecolic LRYGBP between August 2003 and February 2007. Early weight
      loss and the incidence of GJS strictures or leaks and wound infections were
      compared between circular-stapled anastomosis (CSA) and linear-stapled
      anastomosis (LSA). Both groups were matched for age, sex, and body mass index.
      RESULTS: Excess weight loss at 3 months was slightly better with the CSA (p =
      0.002) and comparable thereafter. Percentage of excess weight loss at 6, 12, and
      24 months was 55.9 +/- 17.5% vs. 51.2 +/- 14.5%, 69.5 +/- 20.9% vs. 71.4 +/-
      22.6%, and 70.8 +/- 22.4% vs. 73.2 +/- 23.4%, respectively (CSA vs. LSA).
      Strictures at the GJS were found only in the CSA group (n = 4), and leaks were
      found in one patient of the CSA group. More wound infections were observed in
      patients of the CSA group (ten vs. one). CONCLUSIONS: CSA and LSA lead to
      comparable early weight loss in LRYGB. Thus, the technique is the surgeon's
      choice. In CSA, a higher incidence of GJS strictures and wound infections was
      observed. As weight regain following LRYGBP is commonly observed after at least 3
      years, a longer follow-up is needed to compare the incidence of weight regain in
      circular- vs. linear-stapled GJS.

PMID- 19856036
TI  - Diagnosis and treatment of atypical presentations of hiatal hernia following
      bariatric surgery.
AB  - Bariatric surgery dramatically alters the normal stomach anatomy resulting in a
      significant incidence of hiatal hernia and gastroesophageal reflux disease.
      Although the majority of patients remain asymptomatic, many complain of severe
      heartburn refractory to medical management and additional highly atypical
      symptoms. Here, we describe the diagnosis and treatment regarding four cases of
      symptomatic hiatal hernia following bariatric surgery presenting with atypical
      symptoms in the University Hospital, USA. Four patients presented following
      laparoscopic Roux-en-Y gastric bypass or duodenal switch/pancreaticobiliary
      bypass (DS) with disabling and intractable midepigastric abdominal pain
      characterized as severe and radiating to the jaw, left shoulder, and midscapular
      area. The pain in all cases was described as paroxysmal and not necessarily
      associated with eating. All four patients also experienced nausea, vomiting, and
      failure to thrive at various intervals following laparoscopic bariatric surgery.
      Routine workup failed to produce any clear mechanical cause of these symptoms.
      However, complimentary use of multidetector CT and upper gastrointestinal
      contrast studies eventually revealed the diagnosis of hiatal hernia. Exploration
      identified the presence of a type I hiatal hernia in all four patients, with the
      stomach staple lines densely adherent to the diaphragm and parietal peritoneum.
      Operative intervention led to immediate and complete resolution of symptoms. The
      presence of a hiatal hernia following bariatric surgery can present with highly
      atypical symptoms that do not resolve without operative intervention. Recognition
      of this problem should lead to the consideration of surgery in cases where
      patients are dependent on artificial nutritional support and whose symptoms are
      poorly controlled with medication alone.

PMID- 19856037
TI  - The classic: a study of the weak foot, with reference to its causes, its
      diagnosis, and its cure; with an analysis of a thousand cases of so-called flat
      foot. 1896.

PMID- 19856039
TI  - Sonographic assessment of the conventional 'blind' ilioinguinal block.

PMID- 19856038
TI  - The classic: Symposium on arthroplasty: arthroplasty: experimental and clinical
      methods. 1918.

PMID- 19856040
TI  - Spinal mepivacaine with fentanyl for outpatient knee arthroscopy surgery: a
      randomized controlled trial.
AB  - BACKGROUND: The foremost limitation of local anesthetic solutions for spinal
      anesthesia in the outpatient setting is prolonged motor blockade and delayed
      ambulation. The purpose of this study was to determine if the addition of
      intrathecal fentanyl to low-dose spinal mepivacaine provides adequate anesthesia
      with shorter duration of functional motor blockade for ambulatory knee surgery
      compared with spinal mepivacaine alone. METHODS: Following institutional review
      board approval and informed consent, 34 patients undergoing unilateral knee
      arthroscopy were enrolled in this study. The patients were randomly assigned to
      receive either 30 mg of isobaric mepivacaine 1.5% plus fentanyl 10 microg (M + F
      group) or 45 mg of isobaric mepivacaine 1.5% alone (M group) intrathecally.
      Postoperatively, the times to achieve sensory block regression to the S1
      dermatome and to attain functional motor block recovery enabling ambulation were
      recorded. All assessments were blinded. RESULTS: The time to completion of Phase
      I recovery was shorter in the M + F group (104.6 +/- 28.4 min) than in the M
      group (129.1 +/- 30.4 min; P = 0.023). Regression of sensory blockade to S1 was
      earlier in the M + F group (118.4 +/- 53.5 min) than in the M group (169.7 +/-
      38.9 min; P = 0.003). Patients in the M + F group (176.4 +/- 40.3 min) were able
      to ambulate significantly earlier than those in the M group (205.6 +/- 31.4 min;
      P = 0.025). No cases of transient or persistent neurological dysfunction were
      noted. CONCLUSIONS: When compared with 45 mg isobaric mepivacaine 1.5%, an
      intrathecal dose of 30 mg isobaric mepivacaine 1.5% plus 10 microg fentanyl
      produces reliable anesthesia, hastens block regression, shortens stay in Phase I
      recovery, and enables earlier ambulation for patients undergoing unilateral knee
      arthroscopy (Registration no. NCT00803725).

PMID- 19856041
TI  - Mikulicz's disease with severe thrombocytopenia following autologous stem cell
      transplantation in a multiple myeloma patient.
AB  - We report the first case of Mikulicz's disease (MD) occurring 2 years after
      autologous peripheral blood stem cell transplantation (PBSCT) for multiple
      myeloma (MM). A 70-year-old man developed bilateral enlargement of parotid and
      submandibular glands. The patient had previously received 2 courses of autologous
      PBSCT for IgG-kappa type MM, and had been stable for 2 years. This salivary gland
      enlargement was initially felt to represent a recurrence of MM, since along with
      gland swelling, IgG was also elevated. However, repeated biopsy of the left
      submandibular gland revealed chronic sclerosing sialadenitis rather than
      plasmacytoma. Results of salivary gland scintigraphy, serological testing, and
      absence of sicca symptoms also supported the diagnosis of MD. Concurrently, the
      patient developed severe thrombocytopenia (0.8 x 10(4)/microl). Bone marrow
      biopsy showed abundant megakaryocytes, suggesting enhanced platelet destruction.
      After high-dose steroid and immunoglobulin therapy, the platelet count gradually
      returned to normal with complete resolution of the salivary gland enlargement. No
      apparent signs of MM recurrence were documented during these clinical events.

PMID- 19856042
TI  - Ovarian cancer in endometriosis.

PMID- 19856043
TI  - Ovarian cancer in endometriosis: epidemiology, natural history, and clinical
      diagnosis.
AB  - We review whether endometriosis-associated ovarian cancer is a specific entity
      compared with ovarian cancer not associated with endometriosis, with respect to
      epidemiology, natural history, and clinical diagnosis; we present a review of the
      English-language literature for ovarian cancer in endometriosis with respect to
      these three features. A recent prospective study in Japan directly showed that,
      during a follow-up of up to 17 years of an ovarian endometrioma cohort (n =
      6398), 46 incident ovarian cancers were identified, showing that the ovarian
      cancer risk was significantly elevated in patients with ovarian endometrioma
      (standardized incidence ratio [SIR], 8.95; 95% confidence interval [CI], 4.12 to
      15.3). Advancing age (>40 years) and the size of the endometriomas (>9 cm) were
      independent predictors of the development of ovarian cancer among the women with
      ovarian endometrioma. Although some endometriosis lesions may predispose to clear
      cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) of the ovary, both of
      these cancers differ from the other histological types with respect to their
      clinical characteristics and carcinogenesis. In patients with endometriosis
      associated ovarian cancer, benign-appearing ovarian masses are typically present
      several years before the diagnosis of the cancer. A slightly elevated
      carbohydrate antigen [CA] 125 level is also typically present many years before
      the diagnosis in these patients. However, serous-type ovarian cancer may exhibit
      a rapid progression possibly through de-novo carcinogenesis. Ovarian endometrioma
      could be viewed as a neoplastic process, particularly in perimenopausal women.
      Understanding the mechanisms of the development of endometriosis and elucidating
      its pathogenesis and pathophysiology are intrinsic to the prevention of
      endometriosis-associated ovarian cancer and the search for effective therapies.

PMID- 19856044
TI  - Ovarian cancer in endometriosis: molecular biology, pathology, and clinical
      management.
AB  - Recent molecular and pathological evidence suggests that endometriosis is a
      monoclonal, neoplastic disease. Moreover, endometriosis serves as a precursor of
      ovarian cancer (endometriosis-associated ovarian cancer; EAOC), especially of the
      endometrioid and clear cell subtypes. Although a variety of molecular events,
      such as p53 alteration, PTEN silencing, K-ras mutations, and HNF-1 activation,
      have been identified in EAOC, its precise carcinogenic mechanism remains poorly
      understood. Our recent data indicate that microenvironmental factors, including
      oxidative stress and inflammation, play an important role in the carcinogenesis
      and phenotype of EAOC. The management of endometriosis from the standpoint of
      EAOC is not standardized yet. To this end, clarification of the precise natural
      course and the risk factors that contribute to malignant transformation remain
      important goals. Among the phenotypes of EAOC, clear cell carcinoma, seems to
      require a specific treatment strategy, including molecular targeting.

PMID- 19856045
TI  - Management of patients with pregnancy-associated gastric cancer in Japan: a mini
      review.
AB  - Gastric cancer associated with pregnancy is quite rare, and is most often
      diagnosed at an advanced stage. Furthermore, physicians are confronted with two
      conflicting issues in this condition: the need for early treatment of the
      maternal gastric cancer and the continuation of the pregnancy. To clarify the
      characteristics of pregnancy-associated gastric cancer and to obtain useful
      information that would help us choose the best treatment strategy for pregnancy
      associated gastric cancer, we reviewed the existing literature, using the key
      words "pregnancy" and "gastric cancer". We were able to accumulate 136 cases,
      including 100 cases reported previously in Japan, and 1 case that we report here.
      We analyzed a total of 137 cases in the present study. With respect to the stage
      of gastric cancer, 92.5% of the patients studied had advanced gastric cancer, and
      only 45.3% of the patients underwent gastrectomy, including incomplete resection.
      Accordingly, the prognosis was very poor; the 1- and 2-year survival rates were
      18.0% and 15.1%, respectively. However, the number of patients found to have
      early gastric cancer by endoscopic examination has been increasing recently. An
      endoscopic examination should be conducted immediately in pregnant patients
      presenting with persistent gastrointestinal symptoms for the differential
      diagnosis of hyperemesis gravidarum. When an endoscopic examination reveals that
      pregnant patients have gastric cancer, a therapeutic plan should be promptly
      formulated, in accordance with the number of weeks of gestation, by a medical
      team consisting of specialists in perinatal obstetrics and gastric cancer
      specialists.

PMID- 19856046
TI  - Oxaliplatin-induced allergic reaction in patients with colorectal cancer in
      Japan.
AB  - BACKGROUND: Oxaliplatin is a platinum compound that is clinically effective for
      colorectal cancer (CRC), in combination with 5-fluorouracil (5-FU) and leucovorin
      (LV), and it is widely used for metastatic disease and for the adjuvant treatment
      of stage III CRC. With the increasing use of oxaliplatin in Japan, serious
      adverse events have been experienced other than hematologic and neurologic
      toxicities. METHODS: In order to clarify the clinical features of allergic
      reactions to oxaliplatin, we retrospectively investigated CRC patients who had
      received oxaliplatin-based chemotherapies. RESULTS: One hundred and twenty-five
      CRC patients who had been treated with FOLFOX regimens (containing oxaliplatin, 5
      FU, and LV) were examined, and 21 patients (17%) were found to have developed
      allergic reactions. Sixteen patients (13%) had grade 1/2 adverse events,
      classified according to the common terminology criteria for adverse events (CTC
      AE) version 3.0 and 5 (4%) had grade 3/4 adverse events. The allergic reaction
      appeared after a median number of nine cycles (range, 2-15 cycles). Previous
      chemotherapy included 5-FU/LV, CPT-11, and S-1. All of the patients with allergic
      reactions recovered completely when treated with antiallergy drugs. Oxaliplatin
      was reintroduced in 11 patients, with the use of prophylactic agents; allergic
      reaction to the reintroduction was not observed in 8 patients and grade 1/2
      allergic reactions developed in 3 patients. No correlation was identified between
      allergic reaction and patients' background characteristics such as sex, history
      of allergy, and profile of other adverse events. CONCLUSION: Allergic reactions
      to oxaliplatin remain an important issue for patients being able to safely
      continue effective chemotherapies; further analysis will be needed to establish
      methods for the prediction and prophylaxis of such reactions.

PMID- 19856047
TI  - Clinical compliance with an oral uracil/tegafur (UFT) plus leucovorin (LV)
      regimen as adjuvant chemotherapy in Japanese colorectal cancer patients.
AB  - BACKGROUND: The combination of oral uracil/tegafur (UFT) plus leucovorin (LV) is
      widely accepted as adjuvant chemotherapy for stages II and III of colorectal
      cancer. However, the clinical compliance of Japanese patients with this regimen
      has not been clearly elucidated to date. METHODS: A total of 40 Japanese
      outpatients were treated with oral UFT plus LV as adjuvant chemotherapy following
      colorectal cancer surgery between January 2005 and June 2007. UFT capsules (300
      500 mg/body per day) and LV tablets (75 mg/body per day, administered with each
      dose of UFT) were to be taken for 28 days, followed by 7 days of rest, with this
      cycle repeated every 35 days for 6 months or until recurrence. The patients were
      classified into the following three groups based on compliance: the completed
      group (n = 21), the modified group (n = 12), and the discontinued group (n = 7).
      RESULTS: The UFT doses (mean +/- SD) were 267 +/- 35 mg/m(2) in the completed
      group, 276 +/- 50 mg/m(2) in the modified group, and 288 +/- 22 mg/m(2) in the
      discontinued group. The UFT dose in the discontinued group tended to be higher
      than that in the completed group (P = 0.12). The most frequent symptoms of
      nonhematologic toxicity were appetite loss (45%) and fatigue (45%). There were no
      hematologic or nonhematologic toxicities of grade 3 or 4. CONCLUSION: The regimen
      of oral UFT plus LV produced only low-grade toxicity and was convenient for
      outpatients. It appears that the initial UFT dose might be associated with the
      development of toxicity in the oral UFT plus LV regimen.

PMID- 19856048
TI  - Results of a preliminary study using hypofractionated involved-field radiation
      therapy and concurrent carboplatin/paclitaxel in the treatment of locally
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: We aimed to evaluate the feasibility and efficacy of hypofractionated
      involved-field radiation therapy (IFRT) omitting elective nodal irradiation (ENI)
      with concurrent chemotherapy for locally advanced non-small-cell lung cancer
      (NSCLC). METHODS: Between July 2004 and July 2006, ten patients with locally
      advanced NSCLC were included in this study. One had stage IIIA and 9 had stage
      IIIB disease. The treatment consisted of IFRT in fractions of 2.5 Gy and weekly
      carboplatin (CBDCA)/paclitaxel (PTX). Hypofractionated IFRT with a median total
      dose of 65 Gy with median percent total lung volume exceeding 20 Gy (V20) of
      20.2%, and a median of five courses of chemotherapy with weekly CBDCA (area under
      the curve, 1.5-2.0)/PTX (30-35 mg/m(2)) were given to all patients. RESULTS: The
      median survival time and the 1-, 2-, and 3-year overall survival rates were 29.5
      months and 90.0%, 58.3%, and 43.8%, respectively. No elective nodal failure was
      encountered during the median follow up of 18.2 months. No acute or late
      toxicities of grade 3 or worse were observed. No in-field recurrence occurred in
      the group with a total dose of 67.5 Gy or more, but there was such recurrence in
      83.3% of those in the group with less than 67.5 Gy. CONCLUSION: Hypofractionated
      IFRT with weekly CBDCA/PTX was a feasible treatment regimen. Hypofractionated
      IFRT with a total dose of 67.5 Gy or more could be a promising modality to
      improve the treatment results in patients with locally advanced NSCLC.

PMID- 19856049
TI  - Current therapeutic strategies for anal squamous cell carcinoma in Japan.
AB  - BACKGROUND: In Western countries, chemoradiotherapy (CRT) is well established as
      the standard therapy for stages II/III anal squamous cell carcinoma (ASCC). In
      Japan, the therapeutic modalities for and outcomes of this disease have not been
      clarified because ASCC is quite rare. The Colorectal Cancer Study Group of the
      Japan Clinical Oncology Group (JCOG-CCSG) conducted a survey to determine the
      current therapeutic strategies for ASCC in Japan. METHODS: In July 2006, a
      questionnaire was sent to 49 institutions affiliated with the JCOG-CCSG to gather
      information on numbers of cases, therapeutic modalities, and outcomes. The target
      subjects were patients with stages II/III ASCC, diagnosed from January 2000 to
      December 2004, who were 20-80 years of age with normal major organ function and
      no severe complications. RESULTS: Replies were received from 40 institutions. A
      total of 59 patients satisfied the subject criteria. Detailed information was
      obtained for 55 subjects; 25 (45%) had stage II ASCC and 30 (55%) had stage III
      ASCC. CRT was performed in 25 patients (45%); surgery in 17 (31%); surgery
      combined with radiotherapy (RT), chemotherapy, or CRT in 8 (15%); and RT in 5
      (9%). Complete response rate in CRT was 80% (20/25). The 3-year progression-free
      survival rates for all subjects and for CRT-only subjects were 67% and 77%,
      respectively. CONCLUSION: From 2000 to 2004, only 59 patients with ASCC were
      identified in the JCOG-CCSG survey and about half of them underwent CRT.

PMID- 19856050
TI  - Can hybrid FDG-PET/CT detect subclinical lymph node metastasis of esophageal
      cancer appropriately and contribute to radiation treatment planning? A comparison
      of image-based and pathological findings.
AB  - BACKGROUND: We aimed to determine the appropriateness of adding 18F
      fluorodeoxyglucose (FDG)-positronemission tomography (PET) to computed tomography
      (CT) and other pre-existing diagnostic imaging modalities for detecting
      subclinical lymph node metastasis of esophageal cancer, by comparing images from
      these modalities with the results of histopathological analysis. METHODS: Twenty
      patients who received radical surgery for squamous cell carcinoma of the
      esophagus were examined by PET-CT, and endoscopic ultrasound (EUS) examination
      before surgery. Based on these diagnostic modalities, the clinical target volume
      (CTV) was set as the gross tumor volume (GTV) plus a 1-cm margin.
      Histopathological diagnosis was performed in all patients immediately after
      resection. RESULTS: Fifty-three (3.0%) of 1764 nodes in the 20 patients were
      histopathologically positive for cancer cells. The CTV was not adequate to cover
      these histopathologically detected positive lymph nodes in 8 of 20 patients on
      CT, 5 of 20 on CT+EUS, 7 of 20 on PET-CT, and 5 of 20 on PET-CT+EUS. CONCLUSION:
      The detection rate of subclinical lymph node metastasis did not improve with the
      use of PET-CT, for either the cervical and supraclavicular, mediastinal, or
      abdominal regions. It is not recommended to use FDG-PET or PET-CT alone as a
      diagnostic tool to determine CTV if pathologically involved lymphatic regions are
      to be included in the CTV in the treatment protocol. The accuracy of PET-CT must
      be further improved in order to better detect positive nodes and improve the
      definition of the CTV.

PMID- 19856051
TI  - High-frequency 30-MHz sonography in preoperative assessment of tumor thickness of
      primary melanoma: usefulness in determination of surgical margin and indication
      for sentinel lymph node biopsy.
AB  - BACKGROUND: High-frequency sonographic imaging has been used for the preoperative
      evaluation of primary malignant melanoma. In the present study, to identify the
      usefulness of 30-MHz sonography for determination of the surgical margin and
      indication for sentinel lymph node biopsy, the correlation between sonometric and
      histometric tumor thickness was investigated. METHODS: A total of 74 primary
      melanomas, in patients seen at the dermatology clinic, Shinshu University
      Hospital, from 1998 to 2006, were evaluated using high-frequency sonographic
      equipment with two probes (15 MHz and 30 MHz), and tumor thickness was measured
      using electronic calipers before surgical treatment. All the primary lesions were
      surgically excised and Breslow's tumor thickness was measured histologically.
      RESULTS: In 68 melanomas, excluding 2 lesions of melanoma in situ and 4 lesions
      with poor sonographic images, sonographic and histologic thickness showed good
      correlation (r = 0.887). Particularly, in 26 melanomas affecting the soles of the
      feet, sonographic and histologic thickness showed excellent correlation (r =
      0.945). Regarding the T categorization, in which T1-T4 are divided at 1, 2, and 4
      mm in thickness, the categories determined with sonometry corresponded very well
      to those determined with histometry. The correspondence was particularly
      excellent in thinner primary lesions with thickness around 1 mm. We excised
      almost all these primary melanomas with surgical margins based on the sonometric
      thickness. In 22 patients with sonometric thickness more than 1 mm, sentinel
      lymph node biopsy and/or radical lymphadenectomy was performed. CONCLUSION: High
      frequency sonography (30-MHz) is very useful in the preoperative prediction of
      tumor thickness, particularly in thinner primary lesions, which allows us to
      determine surgical margins and indication for sentinel lymph node biopsy.

PMID- 19856052
TI  - Cardiac safety of trastuzumab as adjuvant treatment for Japanese patients with
      early breast cancer.
AB  - BACKGROUND: Recently, randomized trials revealed that trastuzumab as adjuvant
      treatment was effective in human epidermal growth factor receptor 2 (HER2)
      positive breast cancer patients. Safety information on adjuvant trastuzumab use
      in Japanese patients, especially cardiac toxicity data, is needed. METHODS: We
      retrospectively reviewed 48 patients with early-stage HER2-positive breast cancer
      who were treated with curative surgery and adjuvant trastuzumab at the National
      Cancer Center Hospital East (Kashiwa, Japan). The cardiac safety as well as the
      short-term efficacy of trastuzumab were evaluated. RESULTS: The median age of the
      patients was 54 years. All patients received adjuvant or neoadjuvant cytotoxic
      chemotherapy. Twenty-seven patients (56%) received adjuvant radiation therapy.
      Forty-four patients (92%) received trastuzumab without concurrent cytotoxic
      chemotherapy and 4 patients (8%) on taxanes received trastuzumab concurrently.
      Twenty-five patients completed 1 year of trastuzumab treatment and 5 patients
      completed 2 years of trastuzumab treatment. Nine patients discontinued
      trastuzumab treatment, because of progressive disease (1 patient), decrease in
      left ventricular ejection fraction (LVEF; 2 patients), patient's refusal (4
      patients), and other reasons (2 patients). There were five cardiac events. A
      decrease in LVEF to less than 50% was seen in 2 patients. The relationship
      between trastuzumab treatment and the cardiac events was unclear in 3 patients.
      The median follow-up time was 21.2 months. The disease-free survival (DFS) was
      97.5% at 1 year and 92.9% at 2 years. CONCLUSION: The incidence of cardiac events
      caused by trastuzumab treatment was low in our analysis. Adjuvant trastuzumab
      treatment for up to at least 1 year should be safe for Japanese breast cancer
      patients.

PMID- 19856053
TI  - Salvage chemotherapy with paclitaxel and gemcitabine plus nedaplatin (TGN) as
      part of multidisciplinary therapy in patients with heavily pretreated cisplatin
      refractory germ cell tumors.
AB  - BACKGROUND: We investigated the efficacy and toxicity of a regimen consisting of
      paclitaxel and gemcitabine plus nedaplatin, a derivative of cisplatin (TGN) in
      patients with heavily pretreated cisplatin-refractory germ cell tumors (GCTs).
      METHODS: Fifteen patients with advanced GCTs were treated with the TGN regimen.
      The combination chemotherapy consisted of paclitaxel (210 mg/m(2)) on day 1 and
      gemcitabine (1000 mg/m(2)) on days 1 and 8 in combination with nedaplatin (100
      mg/m(2)) on day 2 every 3 weeks. RESULTS: Patients enrolled in this study had
      been heavily pretreated with a median of 12 platinum-containing cycles (range, 7
      to 26 cycles). Most of the regimens had included paclitaxel and ifosfamide plus
      cisplatin or nedaplatin (TIP/TIN) chemotherapy. The median follow-up period of
      the present study was 15 months. Patients received 2-11 cycles of the TGN
      combination chemotherapy. Six patients received the treatment combined with other
      therapeutic modalities; 2 patients received radiation therapy for retroperitoneal
      lymph node metastasis, 1 patient had cyber-knife radiosurgery for brain
      metastasis and 3 patients had radiofrequency ablation for liver and lung
      metastasis. Seven (46.7%) of the 15 patients achieved an objective response; 6
      had marker-negative partial responses (PRs) and 1 had a marker-positive PR. Two
      (13%) of the 7 patients with PRs achieved a disease-free status after
      chemotherapy combined with RT and followed by surgical resection. However, 10
      patients died of the disease and 3 patients are still alive with the disease.
      CONCLUSION: The TGN regimen alone had limited efficacy in this patient
      population, with severe but manageable toxicities. However, TGN chemotherapy may
      offer a chance of cure for some heavily pretreated cisplatin-refractory (TIP/TIN
      refractory) patients as part of multidisciplinary therapy.

PMID- 19856054
TI  - The contribution of limited-resource countries to the American Society of
      Clinical Oncology annual meetings.
AB  - BACKGROUND: Limited-resource countries (LRCs) are underrepresented in biomedical
      research, and data with respect to oncology are lacking. The aim of the present
      study was to assess the participation of LRCs in the American Society of Clinical
      Oncology (ASCO) annual meetings. METHODS: We analyzed the characteristics of
      abstracts originating from LRCs presented at the 2005-2007 ASCO meetings. We used
      a logistic regression model to identify country characteristics associated with
      contributions to the meetings. RESULTS: Eight percent of abstracts were generated
      by authors from LRCs. Abstracts from LRCs, compared with abstracts originating
      from high-income countries (HICs), were less commonly scheduled for oral and
      poster presentations (1.4% and 26.8% vs 8.8% and 52.8%, respectively; P < 0.001),
      and were less likely to report industry-provided funding (2.0% vs 12.7%; P <
      0.001). However, the presentation type and the rate of reporting industry funding
      did not significantly differ between HIC abstracts and LRC abstracts involving
      one or more coauthors from HICs. In multivariate analysis, ASCO-related
      characteristics, but not geoeconomic parameters, were significantly predictive of
      country participation in the meetings. CONCLUSION: These data show that the
      contribution of LRCs to ASCO annual meetings is very low. Although abstracts
      originating from LRCs involving authors from HICs were associated with a higher
      impact type of presentation, their relevance to the cancer care concerns of LRCs
      remains to be ascertained.

PMID- 19856055
TI  - Meningeal dissemination from an ovarian carcinoma with effective response to
      intrathecal chemotherapy.
AB  - Meningeal dissemination is rare in the clinical course of ovarian carcinoma, and
      its prognosis is poor. Although it is treated by the intrathecal administration
      of methotrexate (MTX) and/or total brain irradiation, these treatments are
      usually ineffective. We report a 58-year-old woman with stage IIIc ovarian cancer
      who had received nine courses of adjuvant chemotherapy after surgery. But her
      carbohydrate antigen (CA) 125 serum level had increased further (38.9 U/ml) after
      five courses of biweekly paclitaxel (Taxol; Bristol-Myers Squibb, Tokyo, Japan;
      BT) maintenance therapy. Fainting occurred, with a few seconds of
      unconsciousness, as did severe headaches. However, results of head computed
      tomography (CT), head magnetic resonance imaging, and electroencephalogram were
      normal. Lumbar puncture (LP) was performed. The opening pressure was 30 cmH2O or
      greater. Meningeal dissemination of the ovarian cancer was diagnosed, as
      adenocarcinoma cells were found by cerebrospinal fluid (CSF) cytology. We started
      chemotherapy with intrathecal injections of MTX and hydrocortisone acetate.
      Establishing a diagnosis of carcinomatous meningitis may be difficult. Clinical
      signs and biological data are not conclusive. In this patient, CSF cytology was
      very effective in establishing the diagnosis, and the intrathecal administration
      of MTX and hydrocortisone was very effective.

PMID- 19856056
TI  - Placental site trophoblastic tumor (PSTT) with multiple metastases and extremely
      poor prognosis.
AB  - Placental site trophoblastic tumor (PSTT) is a rare type of gestational
      trophoblastic disease. There is a wide clinical spectrum of presentation and
      behavior ranging from a benign condition to an aggressive disease with a fatal
      outcome. PSTT limited to the uterus is in a good prognosis group, but PSTT with
      metastasis is a lethal disease. We document a case of PSTT with multiple
      metastases and extremely poor prognosis. A 36-year-old woman had abnormal
      irregular vaginal bleeding 14 months after her third pregnancy and delivery. The
      mitotic count of the tumor cells was quite high (23/10 high-power fields). It
      would have been difficult to remove the tumor by surgery because of the tumor
      size and its invasion, so we suggested chemotherapy. We treated her with EMA/CO
      (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) as a
      first-line regimen. During the sixth cycle of EMA/CO, the disease became drug
      resistant and she died 8 months after the first symptom. This was a rare case
      among documented patients with PSTT with metastasis, with the patient having
      short-term survival (<1 year). We conclude that a high mitotic count and atypical
      undifferentiated pathological features are significant poor prognostic factors
      for survival in PSTT.

PMID- 19856057
TI  - Interstitial pneumonia arising in a patient treated with oxaliplatin, 5
      fluorouracil, and, leucovorin (FOLFOX).
AB  - Information concerning the pulmonary toxicity of oxaliplatin with infusional 5
      fluorouracil plus leucovorin (FOLFOX) is very limited. We herein report the case
      of a patient with FOLFOX-induced interstitial pneumonia. An 82-year-old man with
      unresectable colon cancer liver metastases was referred to our department for
      chemotherapy with the FOLFOX protocol. After the administration of ten cycles, he
      visited our outpatient clinic with a 2-week history of coughing and shortness of
      breath; he was afebrile. A chest radiograph showed reticular shadows with ground
      glass opacities mainly involving the middle and lower zones of the right lung.
      Computed tomography depicted ground-glass opacities with superimposed
      reticulation in the right lung. A diagnosis of FOLFOX-induced interstitial
      pneumonia was made based on the clinical course and imaging findings. The
      symptoms disappeared within 3 days after the cessation of the FOLFOX regimen and
      the initiation of high-dose corticosteroid treatment. Two months after the
      initiation of the corticosteroid treatment, complete remission of the
      radiological abnormalities was confirmed; thereafter, interstitial pneumonia did
      not recur despite the reintroduction of 5-fluorouracil/leucovorin alone,
      suggesting that 5-fluorouracil/leucovorin alone was not responsible for the
      development of the interstitial pneumonia. Thus, oxaliplatin, alone or in
      combination with 5-fluorouracil/leucovorin, may have caused the interstitial
      pneumonia in this patient. Once interstitial pneumonia has occurred, cessation of
      the regimen is mandatory, and high-dose corticosteroid treatment is commonly
      given to rescue patients from this potentially lethal complication.

PMID- 19856058
TI  - Biliopancreatic fistula and abscess formation in the bursa omentalis associated
      with intraductal papillary mucinous cancer of the pancreas.
AB  - We describe an unusual case of biliopancreatic fistula, free perforation, and
      subsequent abscess formation within the lesser peritoneal sac associated with
      intraductal papillary mucinous carcinoma (IPMC). A 71-year-old man presented with
      general fatigue and loss of appetite that had persisted for 1 month. Abdominal
      computed tomography (CT) revealed findings consistent with an intraductal
      papillary mucinous neoplasm (IPMN) of the pancreas, accompanied by abscess
      formation in the bursa omentalis. Gastrointestinal fiberscopy revealed a swollen
      papilla of Vater expanded by sticky mucus, and a communication between the
      pancreatic duct and bile duct was demonstrated by the injection of indigo carmine
      solution into the pancreatic duct. Percutaneous transhepatic abscess drainage
      (PTAD) was performed on the day of admission. After this procedure, the patient
      was managed for 1 month and supported nutritionally with glycemic control for
      diabetes mellitus. After admission, the patient had an episode of obstructive
      jaundice that was treated by retrograde biliary drainage. Pancreaticoduodenectomy
      with lymph node dissection was then performed. Pathological examination revealed
      IPMN with patchy, scattered carcinoma of the pancreatic head and uncinate process
      with the formation of a biliopancreatic fistula. Bile duct epithelium in the area
      of the biliopancreatic fistula demonstrated atypical papillary epithelium
      suggestive of tumor invasion.

PMID- 19856059
TI  - Multidisciplinary treatment including sorafenib stabilized the bone metastases of
      renal cell carcinoma in an immunosuppressed renal transplant recipient.
AB  - We report a case of metastatic renal cell carcinoma in the native kidney of a
      renal transplant recipient. The patient was a 57-year-old man in whom a tumor in
      the native kidney and bone metastasis were found incidentally on imaging, 10
      years after cadaveric renal transplantation. Interferon-alpha was administered
      after nephrectomy and following palliative irradiation of the metastasis, but
      could not be continued because of allograft dysfunction. Subsequent
      administration of zoledronic acid and sorafenib stabilized the disease for 18
      months after nephrectomy. This is the first reported case of sorafenib
      administration to a renal transplant recipient with metastatic renal cell
      carcinoma.

PMID- 19856060
TI  - Combined chemotherapy with carboplatin plus irinotecan showed favorable efficacy
      in a patient with relapsed small cell carcinoma of the prostate complicated with
      meningeal carcinomatosis.
AB  - We report the case of a 65-year-old man with recurrent prostate cancer who
      presented with meningeal carcinomatosis. In September 2007, he had been diagnosed
      with mixed type small cell carcinoma and adenocarcinoma at clinical stage T4N1M1
      (primary prostate tumor with multiple bone, liver, and lymph node metastases) and
      hormonal therapy had been administered. Following an increase in the level of pro
      gastrin-releasing peptide (ProGRP), combined chemotherapy with cisplatin plus
      etoposide was implemented and showed efficacy in targeting the small cell
      carcinoma. In March 2008, he presented with signs of meningeal irritation; his
      condition deteriorated quickly and multiple brain metastases were confirmed by
      magnetic resonance imaging (MRI). A sample of cerebrospinal fluid collected by
      lumbar puncture showed cancer cells and an elevated level of ProGRP. Small cell
      carcinoma of the prostate complicated with meningeal carcinomatosis was
      diagnosed. A different chemotherapy regimen was then administered, consisting of
      a combination of carboplatin plus irinotecan, which is one of the most common
      first-line treatments for extensive-stage small cell lung carcinoma. From day 20
      after the initiation of this therapy, he gradually recovered from the signs of
      meningeal irritation, and brain MRI showed nearly normal findings; also, the
      serum level of ProGRP was reduced. In conclusion, we report the efficacy of
      combined treatment with carboplatin plus irinotecan for small cell carcinoma of
      the prostate complicated with meningeal carcinomatosis. Because this clinical
      condition is extremely rare, a gold standard treatment has yet to be established.

PMID- 19856061
TI  - Successful outcome after resection of liver metastasis arising from an
      extraadrenal retroperitoneal paraganglioma that appeared 9 years after surgical
      excision of the primary lesion.
AB  - A 54-year-old man underwent surgery for excision of a retroperitoneal tumor that
      measured 12 cm in diameter, and histopathological examination revealed the tumor
      was an extraadrenal retroperitoneal paraganglioma. He presented 9 years later
      with epigastric discomfort. Abdominal ultrasound showed a solitary liver tumor.
      The diagnosis, based on radiological workup, was metastatic paraganglioma. The
      tumor was surgically resected and the histological findings resembled those of
      the primary tumor. The patient has been followed up for 3 years and remains
      recurrence-free. Surgical resection is an effective treatment approach for
      primary and secondary paragangliomas, but the resectability of liver metastatic
      lesions is usually low, although complete resection with a wide surgical margin
      was possible in this patient. This case suggests that a good prognosis after the
      resection of hepatic metastasis depends not only on the curative resection of the
      metastatic lesion but also on the tumor characteristics, such as slow growth or
      low aggressiveness.

PMID- 19856062
TI  - Successful treatment of metastatic pancreatic adenocarcinoma with combination
      chemotherapy regimens.
AB  - Pancreatic adenocarcinoma is the fourth leading cause of cancer deaths in the
      United States. Current 5-year survival is less than 4%, highlighting the dire
      need for effective treatment. We report the case of a 41-year-old woman who was
      diagnosed with advanced metastatic well-to-moderately differentiated mucinous
      adenocarcinoma of the pancreas, involving the liver and peritoneal cavity. She
      agreed to receive novel combination chemotherapy rather than the standard-of-care
      treatment. This patient was treated with three unique combination regimens.
      Complete response of multiple liver and peritoneal metastases and reduction in
      size with increasing calcification of the pancreatic mass occurred in this
      patient after 18 months of treatment. This report documents the individual
      response to effective and well-tolerated treatment regimens integrating available
      drugs.

PMID- 19856063
TI  - Characterization of beta-lactam antibiotic-induced vancomycin-resistant MRSA
      (BIVR) in a patient with septicemia during long-term vancomycin administration.
AB  - It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show
      resistance to vancomycin (VCM) and beta-lactam antibiotics; thus, they are termed
      beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of
      MRSA is induced by the administration of beta-lactam antibiotics, but this
      phenomenon can be difficult to detect in the clinical laboratory. We detected the
      BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly
      into the windpipe during long-term VCM therapy. The patient was diagnosed with
      MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin
      (SBT/ABPC) was administered for 5 days. However, the fever recurred, and
      administration of VCM was resumed for 7 days from July 19. Fever developed again,
      and VCM was administered again for 14 days from September 30. BIVR and VCM-low
      sensitive MRSA were isolated from blood on October 18 and 22, although the VCM
      trough concentration was 10.2 microg/ml. On October 27, we changed to a
      combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever
      quickly decreased and the clinical symptoms abated. We isolated five MRSA strains
      from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of
      BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns
      determined by pulsed-field gel electrophoresis were completely identical except
      for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM
      low-sensitive MRSA became sensitive to beta-lactam antibiotics. Our results
      indicate the possibility that long-term VCM therapy is one of the factors that
      allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for
      MRSA to fail.

PMID- 19856065
TI  - Nonspecific interstitial pneumonia pattern as pulmonary involvement in human T
      cell lymphotropic virus type 1 carriers.
AB  - It is well established that diffuse interstitial shadows are observed in human T
      cell lymphotropic virus type 1 (HTLV-1) carriers. However, the pathological
      pattern of nonspecific interstitial pneumonia (NSIP) has rarely been reported.
      Here, we describe the clinical features of four patients with histologically
      proven NSIP and HTLV-1 infection. The patients, one woman and three men, had a
      median age of 59.5 years. High-resolution computed tomography of the lungs was
      performed in all patients, and no apparent honeycomb formations were detected.
      The present study demonstrates that the NSIP pattern is a significant
      pathological classification of interstitial pneumonia associated with HTLV-1
      carriers.

PMID- 19856064
TI  - The inhibitory effect of vancomycin ointment on the manifestation of MRSA
      keratitis in rabbits.
AB  - The purpose of this study was to investigate an experimental model of methicillin
      resistant Staphylococcus aureus (MRSA) keratitis, and to evaluate the inhibitory
      effect of vancomycin ointment on the manifestation of keratitis in this model.
      For the development of the MRSA keratitis model, 16 rabbits received 0.3-ml
      intrastromal injections of 1 x 10(7) colony forming units/ml MRSA inoculated to
      each of their corneas. After the MRSA inoculation, the rabbits were examined for
      a period of 14 days. Vehicle only was applied to each left eye for 2 days as an
      experimental control. Prototype vancomycin ointments, at concentrations of 0.03%,
      0.1%, 0.3%, and 1.0%, were applied to each right eye for 2 days. The treatment
      commenced immediately after the MRSA inoculation and was administered five times
      a day at 2-h intervals. Four rabbits were used for each vancomycin ointment
      concentration. Anterior segments were examined daily, and the minimum inhibitory
      concentration of vancomycin (percentage in the ointment) for treating MRSA
      keratitis was determined on day 2. On day 14, no recurrences of infection were
      observed in the eyes that had not exhibited keratitis on day 2. Forty-eight hours
      post-inoculation, all left eyes demonstrated severe conjunctivitis, stromal
      infiltrates at injection sites, and fibroid reactions in the anterior chamber.
      MRSA keratitis was completely inhibited by 0.3% and 1.0% vancomycin ointments.
      Although the 0.1% ointment generally could prevent keratitis, punctate
      infiltrates were found in some eyes. Numerous infiltrates were found in eyes
      treated with 0.03% ointment. In conclusion, the present study substantiates the
      view that vancomycin ointment has a potent inhibitory effect upon the
      manifestations of MRSA keratitis, and indicates that a 0.3% concentration is
      necessary for effective treatment.

PMID- 19856066
TI  - Clinical evaluation of QuantiFERON TB-2G test in patients with healed pulmonary
      tuberculosis.
AB  - We evaluated the response to the QuantiFERON TB-2G (QFT-2G) test in patients with
      healed pulmonary tuberculosis (TB) compared to the response in those with active
      pulmonary TB. The subjects were 208 patients with healed pulmonary TB and 155
      patients with active pulmonary TB. The QFT-2G test results were analyzed by
      stratifying them into 5- or 10-year periods after the completion of
      antituberculosis treatment. Of the 208 patients with healed pulmonary TB, 63% had
      a positive tuberculin skin test (TST) and 34% had a positive QFT-2G test result.
      There was no significant difference in the positive response rate for the QFT-2G
      test, or in the positive test result rate for only the early secretory antigenin
      target 6-kD protein (ESAT-6) antigen, only the culture filtrate protein 10 (CFP
      10) antigen, or both the ESAT-6 and CFP-10 antigens among any subgroups
      stratified by 5- or 10-year periods after the completion of antituberculosis
      treatment. The positive rate for the QFT-2G test was significantly higher in
      patients with active pulmonary TB (83%) than in patients with healed pulmonary TB
      (34%). Regarding the combined and separate responses to both the ESAT-6 and CFP
      10 antigens, the positive response rate for both antigens was significantly lower
      in patients with healed pulmonary TB than in those with active pulmonary TB.
      Because many patients continued to show a positive response to the QFT-2G test
      even when a long period had passed after the completion of the antituberculosis
      treatment, it is suggested that, in patients with a previous history of TB,
      particular attention must be paid to the relapse of TB or reinfection with TB.

PMID- 19856067
TI  - Population pharmacokinetics of oral levofloxacin 500 mg once-daily dosage in
      community-acquired lower respiratory tract infections: results of a prospective
      multicenter study in China.
AB  - This study aimed to explore the pharmacokinetic features of levofloxacin (LVFX)
      in Chinese patients with infections and to confirm oral LVFX 500 mg once daily as
      an optimal treatment regimen based on pharmacokinetic-pharmacodynamic (PK-PD)
      analysis. A total of 1052 plasma samples from 164 Chinese adult patients with
      community acquired lower respiratory tract infections (CALRTIs) and 18 healthy
      volunteers were used for population PK analysis. LVFX 500-mg tablets were given
      once daily. A nonlinear mixed effects model (NONMEM) program was used for
      population PK model-building and a two-compartment model with first-order
      absorption process was established. Creatinine clearance (CL(cr)) and body weight
      were identified as intrinsic factors which significantly affected oral clearance
      (CL(t)/F) and the apparent volume of distribution of the central compartment
      (V1/F), respectively. The final model is described as follows: CL(t)/F (l/h) =
      (8.97 + 0.917 x (CL(cr) (ml/min)-100.92) x 60/1000) x exp (eta(CLt/F)). V1/F (l)
      = (85.3 + 1.22 x (weight (kg)-60.75)) x exp (eta(V1/F)). Q/F (l/h) = 0.351. V2/F
      (l) = 6.81. k(a) (h(-1)) = 1.44 x exp(eta(ka)). Based on the population PK model,
      mean C(max) and AUC(0-24h) in CALRTI patients were estimated as 5.13 microg/ml
      and 58.98 microg.h/ml, respectively. A subgroup analysis showed that patients
      with mild renal dysfunction (50 ml/min < or = CL(cr) < 80 ml/min) had 34% higher
      AUC(0-24h) values compared to patients with normal renal function (CL(cr) > or =
      80 ml/min). Postmodeling simulation using final population PK estimates also
      showed that C(max) and AUC(0-24h) increased markedly in patients with severe
      renal dysfunction. The results indicate that LVFX dosage adjustment should be
      individualized on the basis of the CL(cr), especially in those with CL(cr) less
      than 50 ml/min. None of the PK parameters had any correlation with the occurrence
      of adverse events. PK-PD analysis indicated that, in patients treated with LVFX
      500 mg once daily, the AUC(0-24h)/MIC ratio exceeded the target for those major
      CALRTI pathogens isolated. In addition, the C(max)/MIC ratio reached 5 for
      Streptococcus pneumoniae, indicating that the emergence of LVFX-resistant S.
      pneumoniae could be prevented during the therapy with this dosage regimen. These
      results demonstrate that oral LVFX 500 mg once daily has favorable PK parameters
      and PK-PD features in patients with CALRTIs, and the results strongly support
      this dosage regimen for the treatment of CALRTI.

PMID- 19856068
TI  - Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment
      of lower respiratory tract infections and urinary tract infections: a prospective
      multicenter study in China.
AB  - Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers
      Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good
      clinical efficacy in the treatment of various infections, including lower
      respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To
      evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open
      label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with
      UTIs) at 32 centers in China. In the per-protocol population, the clinical
      efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment
      was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients
      diagnosed with atypical pneumonia the treatment was effective. The
      bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135)
      for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for
      Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs,
      and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were
      89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug
      related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug
      related laboratory abnormalities was 15.7% (191/1213). Common ADRs were
      dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC
      decreased", "alanine aminotransferase (ALT) increased", "aspartate
      aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased".
      All of these events were mentioned in the package inserts of fluoroquinolones
      including LVFX, and most events were mild and transient. Thirty-four patients
      (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found.
      This study concluded that the dosage regimen of LVFX 500 mg once daily was
      effective and tolerable for the treatment of LRTIs and UTIs.

PMID- 19856069
TI  - Infected abdominal aortic aneurysm caused by nontyphoid Salmonella in an
      immunocompromised patient with rheumatoid arthritis.
AB  - Nontyphoid Salmonella strains are important pathogens commonly found worldwide,
      typically causing gastrointestinal illness. Here, we report a case of a 66
      yearold man with an abdominal aortic infected (or so-called mycotic) aneurysm
      caused by Salmonella enterica subsp. enterica serovar Enteritidis (S.
      Enteritidis). He had multiple risk factors for atherosclerosis: age over 60, a
      long history of smoking, an 8-year history of diabetes mellitus, and a 10-year
      history of rheumatoid arthritis treated with low-dose corticosteroids. Although
      he had presented with no episode of diarrhea or abdominal pain, the abdominal
      aortic infected aneurysm was diagnosed by blood cultures and was carefully
      followed up by computed tomography. An abdominal aneurysmectomy and autogenous in
      situ reconstruction were successfully performed consequently. Alertness to the
      possibility of endovascular infection is important, even if there are no symptoms
      except for persistent fever, when treating Salmonella bacteremia in an
      immunocompromised patient, particularly when there are associated atherosclerotic
      risk factors.

PMID- 19856070
TI  - Advanced hepatocellular carcinoma treated effectively with irinotecan via hepatic
      arterial infusion followed by proton beam therapy.
AB  - We report a 48-year-old man with hepatocellular carcinoma (HCC) treated with
      hepatic arterial infusion (HAI) chemotherapy followed by proton beam therapy. The
      HCC lesion in this patient was 88 mm in diameter, with portal vein tumor
      thrombosis in the right lobe of the liver. He was first treated with 5
      fluorouracil, cisplatin, and isovorin, administered by HAI, combined with
      interferon-alpha, and he was subsequently treated with epirubicin and mitomycin-C
      administered by HAI. However, no definite efficacy of either of these treatments
      was observed. Then, after 3 weeks' continuous administration of irinotecan by
      HAI, the tumor size decreased to 68 mm in diameter. However, 3 months after
      reduction of the tumor, the tumor had become enlarged to 100 mm in diameter and
      intrahepatic metastases were prominent. Angiographic findings indicated that the
      HCC was fed not only from the right hepatic artery but also from the left gastric
      and right and left subphrenic arteries. After rearrangement of the arteries, and
      3 months' continuous HAI chemotherapy with irinotecan, plus hyperthermia, the
      tumor size had decreased to 50 mm in diameter. The reduction rate of the main
      tumor according to the Response Evaluation Criteria in Solid Tumors was 43%;
      therefore, the efficacy of this treatment was judged as a partial response. Two
      months after reduction of the tumor, the patient's serum alpha-fetoprotein (AFP)
      level was elevated, and so docetaxel was administered by HAI instead of
      irinotecan. The liver tumors showed gradual enlargement during the administration
      of docetaxel, although the AFP level was suppressed. Proton beam therapy was
      instituted and the liver tumors showed necrosis after this therapy. The patient
      died of hepatic failure and distant metastases 6 years after the onset of HCC. As
      far as we know, this is the first case report of HCC treated effectively with
      irinotecan administered by HAI followed by proton beam therapy in which tumor
      suppression and the long-term survival of the patient were observed.

PMID- 19856071
TI  - Community-acquired Acinetobacter baumannii meningitis in a previously healthy 14
      month-old boy.
AB  - We report a previously healthy 14-month-old boy who developed community-acquired
      Acinetobacter baumannii meningitis. He had no history of immunodeficiency, and
      was brought to Konan Kosei Hospital with a high fever and vomiting. His
      consciousness was clear, but neck stiffness was noted. Examination of the
      cerebrospinal fluid (CSF) revealed a cell count of 10 112/microl; protein, 216
      mg/dl; and glucose, 9 mg/dl. A CSF test kit for bacterial capsular antigens
      (Pastorex Meningitis; Bio-Rad Laboratories) was positive for Haemophilus
      influenzae type b antigen. On day 3 of admission, the microorganism isolated by
      CSF culture was identified as A. baumannii. Therefore, his treatment was changed
      to meropenem hydrate from the initial therapy with panipenem/betamipron and
      ceftriaxone sodium hydrate. Because the CSF cell count remained elevated,
      meropenem hydrate was administered for a total of 19 days. The meningitis
      resolved with no sequelae.

PMID- 19856072
TI  - Acute cholecystitis caused by Haemophilus influenzae in a child.
AB  - A 6-year old girl was admitted to our hospital with high fever and right upper
      quadrant abdominal pain. At 5 years of age she had undergone allogeneic bone
      marrow transplantation because of intractable congenital pure red cell aplasia,
      after which she had asymptomatic cholelithiasis. Imaging studies and laboratory
      findings on admission suggested acute cholecystitis with a gallstone. The patient
      recovered completely after laparoscopic cholecystectomy was performed and was
      discharged on day 7 after the operation. Haemophilus influenzae grew on the
      aspirated purulent bile. It should be noted that H. influenzae can cause
      cholecystitis in children.

PMID- 19856073
TI  - Sacroiliitis infected with group A streptococcus in a child presenting with
      confusion and combativeness.
AB  - Group A streptococcus-associated severe invasive infection (streptococcal toxic
      shock syndrome) has been described. Streptococcal toxic shock syndrome occurs
      when the infecting strain of group A streptococcus produces superantigens.
      Confusion and combativeness are well known as the common symptoms of
      streptococcal toxic shock syndrome. We encountered a child who suffered from
      pyogenic sacroiliitis, with confusion and combativeness. Group A streptococcus
      was isolated from the patient's blood culture. However, his disease did not
      fulfill the criteria of streptococcal toxic shock syndrome. Pyogenic sacroiliitis
      in children is rare, but patients with pyogenic sacroiliitis due to group A
      streptococcus infection could show confusion and combativeness as clinical signs,
      similar to the signs in streptococcal toxic shock syndrome.

PMID- 19856075
TI  - Safety and efficacy of S-1 chemotherapy in recurrent/metastatic head and neck
      cancer.
AB  - S-1 is an oral 5-fluorouracil (5-FU) anticancer agent and has shown promising
      effects in the treatment of a wide range of carcinomas, including head and neck
      cancer. In addition to being used as adjuvant chemotherapy, S-1 is a promising
      agent for palliative treatment. Its ease of administration makes it an ideal drug
      to treat patients in the outpatient setting while maintaining adequate quality of
      life. However, the clinical role of S-1 in patients with recurrent/metastatic
      head and neck cancer is still uncertain. We retrospectively reviewed 16 patients
      with recurrent/metastatic head and neck cancer who received S-1 monotherapy.
      Thirteen patients with squamous cell carcinoma (SCC) and 3 patients with non-SCC
      who had recurrent/metastatic disease received S-1 monotherapy as outpatients. One
      patient with nasopharyngeal undifferentiated carcinoma and 1 patient with
      maxillary adenosquamous carcinoma showed complete response (CR), while all SCC
      patients showed stable disease (SD) or progressive disease (PD). Median time to
      progression (TTP) was 12 weeks. Five patients showed grade 3 and 4 adverse
      reactions, all hematological. Except for one episode of grade 4 leucopenia which
      required hospitalization and granulocyte colony-stimulating factor (GCSF)
      treatment, all adverse events resolved with dose reduction or dose omission. S-1
      was safely administered in outpatients and showed some efficacy in the treatment
      of recurrent/metastatic head and neck cancer in patients who had received
      previous chemotherapy. S-1 could be used as palliative treatment in patients with
      recurrent/metastatic head and neck cancer.

PMID- 19856074
TI  - An AIDS patient with immune reconstitution inflammatory syndrome due to pulmonary
      Mycobacterium kansasii infection during antiretroviral therapy.
AB  - After the recovery of pneumocystis pneumonia, amebiasis, and cytomegalovirus
      duodenal ulcer in a patient with AIDS, antiretroviral therapy was initiated.
      Fever was first noted on the 11th day of administration of the highly active
      antiretroviral therapy (HAART), and chest radiography showed infiltration into
      the right lower lobe of the lung on the 19th day. Bronchoscopy was performed,
      with a tentative diagnosis of pulmonary tuberculosis, but Mycobacterium kansasii
      was eventually identified. M. kansasii may also be a pathogenic organism causing
      immune reconstitution inflammatory syndrome.

PMID- 19856076
TI  - Novel bla(TEM)-positive ampicillin-susceptible strains of Haemophilus influenzae.
AB  - Two ampicillin-susceptible strains of Haemophilus influenzae were found to carry
      blaTEM genes. In one strain ampicillin susceptibility was explained by poor
      expression of a functional TEM-1 enzyme from a putative weak promoter created by
      a mutation in the promoter region of the gene, and in the other by production of
      an inactive mutant TEM enzyme.

PMID- 19856077
TI  - Clindamycin-primaquine versus pentamidine for the second-line treatment of
      pneumocystis pneumonia.
AB  - There are limited data on the efficacy of alternative regimens for treating
      patients with pneumocystis pneumonia (PCP). We compared the efficacy of
      clindamycin-primaquine (C-P) with that of pentamidine as a second line treatment
      for PCP. Among 91 patients receiving trimethoprim-sulfamethoxazole (TMP-SMX) as a
      first-line treatment for PCP, 31 (34%) did not respond and 7 (8%) had adverse
      reactions. Fourteen patients received C-P and 9 received pentamidine as a second
      line regimen because of treatment failure or an adverse reaction to TMP-SMX. The
      response rate of patients to C-P was higher than the response rate to pentamidine
      (9/14; 64% vs 1/9; 11%; P = 0.03).

PMID- 19856079
TI  - Distinct expression patterns of hedgehog ligands between cultured and primary
      colorectal cancers are associated with aberrant methylation of their promoters.
AB  - Ligand-dependent activation of the Hedgehog (Hh) pathway in colorectal cancers
      (CRCs) is controversial, and the regulation mechanism of Hh ligands expression
      remains to be determined. In the present study, the mRNA expressions of Sonic
      hedgehog (SHH), Indian hedgehog (IHH), Patched, Smoothened, and Gli1 were
      examined in four cultured colon cancer cell lines by reverse transcription-PCR.
      Moreover, ligands mRNA expression (SHH and IHH) were examined by reverse
      transcription-PCR, and SHH protein expression by immunohistochemistry in 25
      primary CRCs. The methylation status of SHH and IHH was also investigated by
      bisulfate sequencing or methylation specific PCR. IHH mRNA was completely absent
      in cell lines studied, and expressed at a very low level or not expressed at all
      in primary CRCs. Methylation analysis revealed that IHH promoter was
      hypermethylated in colon cancer cell lines. Absence of SHH mRNA expression and
      hypermethylation of its promoter was also observed in colon cancer cell lines.
      However, high level expression of SHH and hypomethylation of its promoter was
      detected in primary CRCs. In conclusion, ligand dependent activity of Hh pathway
      is inactive in cultured colon cancer cells correlating to ligands
      hypermethylation. In contrast, SHH overexpression, possible consequence of
      promoter hypomethylation, could play a role in the carcinogenesis of primary
      CRCs.

PMID- 19856080
TI  - Phospholipase Cbeta4 isozyme is expressed in human, rat, and murine heart left
      ventricles and in HL-1 cardiomyocytes.
AB  - Phospholipase C-beta (PLCbeta) isozymes (PLCbeta(1) and PLCbeta(3)) have been
      extensively characterized in cardiac tissue, but no data are available for the
      PLCbeta(4) isozyme. In this study, PLCbeta((1-4)) isozymes mRNA relative
      expression was studied by real-time PCR (RT-PCR) in human, rat, and murine left
      ventricle and the presence of PLCbeta(4) isozyme at the protein level was
      confirmed by Western blotting in all species studied. Confocal microscopy
      experiments carried out in HL-1 cardiomyocytes revealed a sarcoplasmic
      subcellular distribution of PLCbeta(4). Although there were unexpected
      significant interspecies differences in the PLCbeta((1-4)) mRNA expression,
      PLCbeta(4) mRNA was the main transcript expressed in all left ventricles studied.
      Thus, whereas in human and rat left ventricles PLCbeta(4) > PLCbeta(3) >
      PLCbeta(2) > PLCbeta(1) mRNA pattern of expression was found, in murine left
      ventricle the pattern of expression was different, i.e., PLCbeta(4) > PLCbeta(1)
      > PLCbeta(3) > PLCbeta(2). However, results obtained in mouse HL-1 cardiomyocytes
      showed PLCbeta(3) approximately PLCbeta(4) > PLCbeta(1) > PLCbeta(2) pattern of
      mRNA expression indicating a probable cell type specific expression of the
      different PLCbeta isozymes in cardiomyocytes. Finally, RT-PCR experiments showed
      a trend, even though not significant (P = 0.067), to increase PLCbeta(4) mRNA
      levels in HL-1 cardiomyocytes after angiotensin II treatment. These results
      demonstrate the presence of PLCbeta(4) in the heart and in HL-1 cardiomyocytes
      showing a different species-dependent pattern of expression of the PLCbeta((1-4))
      transcripts. We discuss the relevance of these findings in relation to the
      development of cardiac hypertrophy.

PMID- 19856081
TI  - The interaction between interferon-induced protein with tetratricopeptide repeats
      1 and eukaryotic elongation factor-1A.
AB  - It has been shown previously that in mammalian cells, interferon-induced protein
      with tetratricopeptide repeats-1(IFIT1) is rapidly synthesized in response to
      viral infection, functions as an inhibitor of translation by binding to the
      eukaryotic initiation factor-3, and consequently assigns resistive activity
      against viral invasion to cells. It has also been reported that IFIT1 is rapidly
      produced in response to other cell stress agents with no direct relation to virus
      such as bacterial lipopolysaccharide and interleukin-1, but its function under
      these non-viral infection cell stress conditions has yet to be elucidated. Here,
      we demonstrate an interaction between IFIT1 and eukaryotic elongation factor-1A
      (eEF1A) both in vitro, using recombinant proteins as bait in pull-down assays,
      and in vivo, using laser confocal microscopy and immunoprecipitation. In
      addition, we report the initial determination of the domain of IFIT1 that
      mediates this interaction. We also display that both IFIT1 and eEF1A protein
      levels are rapidly elevated, prolonged in tumor necrosis factor alpha pre-treated
      Raw264.7 cells, and most of those cells are induced to death by the end of
      investigations. Our results imply that under some stressful stimulations IFIT1
      may participate in cell death pathways by interaction with eEF1A.

PMID- 19856082
TI  - In vitro drug release study of methacrylate polymer blend system: effect of
      polymer blend composition, drug loading and solubilizing surfactants on drug
      release.
AB  - The application of polymers as the drug delivery systems for treating oral
      infections is a relatively new area of research. The present study was to test
      the release of the antibacterial drug chlorhexidine diacetate (CHDA), the
      antifungal drug Nystatin (NYS) and the antiviral drug acyclovir (ACY) from
      polymer blends of poly(ethyl methacrylate) and poly(n-hexyl methacrylate) of
      different compositions. The effects of polymer blend composition, drug loading
      and solubilizing surfactants on the release of the drugs have been studied.
      Measurements of the in vitro rate of drug release showed a sustained release of
      drug over extended periods of time. Drug release rates decreased with increasing
      PEMA content in polymer blends. CHDA release rates increased steadily with
      increasing drug load. The drug release rates increased with the addition of
      surfactants. This study demonstrates that the three therapeutic agents show a
      sustained rate of drug release from polymer blends of PEMA and PHMA over extended
      periods of time. By varying polymer blend compositions as well as the drug
      concentration (loading), it is possible to control the drug release rates to a
      desired value. The drug release rate is enhanced by addition of surfactants that
      solubilize drugs in the polymer blends.

PMID- 19856084
TI  - A non-fluorescent derivative from derivatizing trans, trans-muconic acid with 2
      (2-naphthoxy)ethyl-2-(piperidino)ethanesulfonate.
AB  - trans, trans-Muconic acid (MA) is a polar metabolite of benzene and used as a
      biomarker for monitoring human exposure to benzene. Because MA is a trace
      metabolite, sensitive method is required for its detection. In addition, MA is a
      highly polar compound with dicarboxyl functions that could incur unfavorable
      adsorption on silica-based stationary phase usually used for separation. To
      address these problems, we planned to derivatize MA with a fluorescent reagent 2
      (2-naphthoxy)ethyl-2-(piperidino)ethanesulfonate to give a naphthoxy derivative
      of MA for improving detection sensitivity and chromatographic properties.
      Surprisingly, the resulting derivative shows no fluorescent activity (lambda(ex):
      226 nm; lambda(em): 350 nm). The negative results could be used as an instructive
      example for discussing on fluorescence quenching.

PMID- 19856083
TI  - Rare earth complexes with 3-carbaldehyde chromone-(benzoyl) hydrazone: synthesis,
      characterization, DNA binding studies and antioxidant activity.
AB  - A new ligand, 3-carbaldehyde chromone-(benzoyl) hydrazone (L), was prepared by
      condensation of 3-carbaldehyde chromone with benzoyl hydrazine. Its four rare
      earth complexes have been prepared and characterized on the basis of elemental
      analyses, molar conductivities, mass spectra, (1)H NMR spectra, UV-vis spectra,
      fluorescence studies and IR spectra. The Sm(III) complex exhibits red
      fluorescence under UV light and the fluorescent properties of Sm(III) complex in
      solid state and different solutions were investigated. In addition, the DNA
      binding properties of the ligand and its complexes have been investigated by
      electronic absorption spectroscopy, fluorescence spectra, ethidium bromide
      displacement experiments, iodide quenching experiments, salt effect and viscosity
      measurements. Experimental results suggest that all the compounds can bind to DNA
      via an intercalation binding mode. Furthermore, the antioxidant activities of the
      ligand and its complexes were determined by superoxide and hydroxyl radical
      scavenging methods in vitro. The rare earth complexes were found to possess
      potent antioxidant activities that are better than those of the ligand alone.

PMID- 19856085
TI  - The Culture of Health Survey: a qualitative assessment of a diabetes prevention
      coalition.
AB  - In the past two decades, the fields of public health and social services have
      increasingly turned toward collaborative and community-based approaches to
      address complex health and social issues. One aspect of these approaches has been
      the development and implementation of community coalitions. Coalitions have been
      used to successfully address a wide range of issues, including cancer prevention,
      tobacco use, HIV/AIDS, youth violence, heart disease, diabetes, and sexual
      exploitation of youth runaways. In south Tucson, Arizona the SEAH coalition was
      developed to address diabetes and substance abuse prevention. Using a qualitative
      interview guide, the Culture of Health Survey, this study was aimed at
      identifying community perceptions of the coalition and its effectiveness in the
      areas of community leadership, partnerships, trust, and movement towards positive
      change. We also sought to document the dissemination, throughout a community, of
      information on the activities and functioning of a community based coalition and
      whether or not it was seen as one that held fast to the community values and not
      to individual agendas. Results highlight the importance of outreach, education,
      trust, and partnerships in promoting diabetes prevention through a community
      coalition.

PMID- 19856086
TI  - Addressing health disparities among African Americans: using the stages of change
      model to document attitudes and decisions about nutrition and physical activity.
AB  - Physical activity (PA) and poor fruit/vegetable intake are contributors of health
      disparities among African Americans (AA). In order to design effective
      interventions to address these behaviors, it is essential to assess where
      individuals are in terms of their attitudes and decisions. The aim of this study
      was to use the Stages of Change Model to assess AA's attitudes and decisions
      regarding pertinent health behaviors and provide suggestions about how to address
      them. A survey was administered to 242 low-income, medically underserved adults
      (47% AA, 27% White, and 26% "Others"). The majority was in the SOC's:
      "contemplation" stage for PA (they were considering PA); "maintenance" stage for
      vegetable intake (they had consumed > or =3 vegetable servings daily for > or =6
      months); and in the "contemplation" stage for fruit intake (those grouped as
      "Others" were significantly more likely to be in the "maintenance" stage).
      Although education and awareness are important, this study has implications for
      interventions with greater emphasis on creating environments or providing
      resources to promote or support behavioral change.

PMID- 19856087
TI  - Health indicators of Native Hawaiian and Pacific Islanders in the United States.
AB  - This study aimed to describe health indicators and behaviors of Native Hawaiian
      and Pacific Islander (NHPI) adults and to compare findings to previous reports on
      US NHPI and the US population. A sample of N = 100 (56 M, 44 F) NHPI adults aged
      40-59 years completed an anonymous questionnaire addressing education and
      household income, tobacco use, physical activity, fruit and vegetable (F&V)
      consumption, cancer screening and health status. Objective measures of height and
      weight were taken to calculate body mass index (BMI). The study sample consisted
      of 49% current smokers and the majority was not meeting guidelines for physical
      activity (80%) or F&V consumption (99%). Cancer screening rates ranged from 0 to
      57% and were higher among females. Mean BMI was 33.9 +/- 7.5 kg/m(2) and 95% were
      overweight or obese. While 36.7% were hypertensive, only 11.1% were taking
      prescribed medication. Compared to both the general US population and available
      data for US NHPI, study participants reported higher prevalence of obesity and
      chronic conditions (hypertension, high cholesterol, diabetes, and angina/CHD) and
      lower levels of physical activity, F&V consumption and cancer screening rates.
      Study findings contribute to the limited knowledge regarding health behaviors of
      US NHPI. Comparisons to US data increase evidence of NHPI health disparities,
      while comparisons to previous NHPI studies emphasize the magnitude of unhealthy
      lifestyle behaviors and subsequent adverse health conditions for this particular
      sample. Further improvements to community outreach and recruitment strategies
      could successfully encourage high-risk individuals to participate in health
      promotion and behavior intervention studies to improve NHPI health behaviors.

PMID- 19856088
TI  - West African immigrant families from Mauritania and Senegal in Cincinnati: a
      cultural primer on children's health.
AB  - Similar to many cities in the US, the Greater Cincinnati area has recently had an
      increase in immigrants from other countries. In particular, there is a small but
      growing population of West African immigrants especially from Senegal and
      Mauritania. In order to better understand children's health of West African
      families in the Cincinnati area, in-depth, in-home narrative interviews were
      conducted with ten West African immigrant parents from Senegal and Mauritania.
      Four salient themes about cultural information related to children's health were
      derived from the qualitative analysis: (1) health care practice and expectations
      including barriers; (2) cultural values and identity; (3) health beliefs and
      traditions/customs; and (4) quality of life. It is essential that health care
      providers understand the nuances of working with West African immigrants
      including cultural differences, strengths, challenges and perceptions in order to
      provide these individuals with the most effective health care services.

PMID- 19856089
TI  - Primary care providers' responses to patient-generated family history.
AB  - Family health history is one of the best predictors of an individual's risk for
      common disease, yet it is underutilized in routine care. Although the Surgeon
      General has recommended consumers record their family health history and share it
      with their health care provider, providers' perceptions of patient-generated
      family histories are unknown. To learn more about providers' experience with and
      perceptions about patient-generated family histories, we mailed surveys to 301
      providers and had a response rate of 24% (n = 68). Seventy-three percent felt a
      patient-generated computer pedigree would improve their ability to assess risk as
      compared to their current methods. Seventy percent felt a patient-generated
      computer pedigree would either have no effect on or would increase the number of
      patients that could be seen in a day. Results suggest that providers appreciate
      the potential benefits of patient-generated family histories. Genetic counselors
      and nurses are in a prime position to promote and facilitate the use of patient
      generated family health histories in routine care.

PMID- 19856090
TI  - Characteristics and co-occurrence of adolescent non-suicidal self-injury and
      suicidal behaviours in pediatric emergency crisis services.
AB  - During the potentially tumultuous adolescent period, non-suicidal self-injury
      (NSSI) and suicide attempts are relatively common, particularly amongst youth who
      present to mental health services. These phenomena frequently co-occur but their
      relationship is unclear. This study evaluated clinical data from 468 youth
      between the ages of 12 and 17 years (63.5% female) to determine the incidence of
      NSSI 24 h prior to presentation at emergency crisis services, evaluated the
      overlap between NSSI and suicide attempt, and examined the characteristics of
      different types of self-harm. Half of the adolescents presenting to emergency
      crisis services had self-harmed within the previous 24 h, with most of these
      (91%) classified as NSSI only. The percentage of youth with a suicide attempt was
      5% and the co-occurrence of these two behaviours was 4%. Group differences in
      depressive symptoms, suicidal ideation and impulsivity were identified, with the
      co-occurring NSSI and suicide attempt group presenting with the highest level of
      psychopathology. This study underscores the necessity of assessing suicidal
      ideation and NSSI in all youth presenting to mental health services.

PMID- 19856092
TI  - Women's sexual responses to heterosexual and lesbian erotica: the role of
      stimulus intensity, affective reaction, and sexual history.
AB  - Past research has demonstrated that women do not show a "category-specific"
      genital response to erotic stimuli. That is, on average, heterosexual and lesbian
      women are indistinguishable in terms of their physiological genital responses to
      heterosexual versus lesbian erotica. In two studies with heterosexual women (n =
      28 for Study 1; n = 30 for Study 2) and lesbians (n = 24 for Study 1; n = 25 for
      Study 2), results confirmed that, on average, women did not show category
      specific genital responses or category-specific subjective sexual arousal.
      However, there was evidence of notable within-group variability; many women did
      respond to the stimuli in a category-specific manner. Heterosexual women were
      more likely than lesbian women to demonstrate category-specificity. Findings also
      revealed that category-specificity was associated with multiple factors,
      including affective responses to the erotic stimuli and sexual history. Results
      of this study highlight the complexity of women's sexual identities and sexual
      responses.

PMID- 19856091
TI  - Methamphetamine use, attitudes about condoms, and sexual risk behavior among HIV
      positive men who have sex with men.
AB  - This study examined attitudes about condoms as a moderator of the relationship
      between methamphetamine use and sexual risk behavior in a sample of 297 HIV
      positive, methamphetamine-using men who have sex with men (MSM). To test for a
      moderating effect of attitudes towards condoms, an interaction term was included
      in multiple regression analysis along with age, income, negative condom
      attitudes, frequency of methamphetamine use, and Beck depression score. A post
      hoc analysis was conducted to determine the relations between methamphetamine use
      and unprotected sex for persons with more vs. less negative attitudes toward
      condoms. These analyses indicated that when individuals had more negative
      attitudes toward condoms, the relation between methamphetamine frequency and
      unprotected sex was significant, while among participants with less negative
      attitudes toward condoms, no significant association was found. Addressing
      methamphetamine-using MSM's attitudes about condoms can serve as a form of harm
      reduction for those who are not yet ready or willing to discontinue
      methamphetamine use.

PMID- 19856093
TI  - HIV sexual risk behavior among low-income women experiencing intimate partner
      violence: the role of posttraumatic stress disorder.
AB  - Posttraumatic stress disorder resulting from intimate partner violence (IPV
      related PTSD), drug problems, and alcohol problems were tested as correlates of
      women's sexual risk behavior. Participants were 136 low-income women experiencing
      physical violence by a male partner during the past 6 months. Sexual risk
      behavior was assessed by whether women had unprotected sex with a risky primary
      partner (i.e., HIV-positive, injection drug user, and/or nonmonogamous),
      unprotected sex with a risky nonprimary partner (i.e. HIV-positive or unknown
      status), or traded sex during the past 6 months. Nearly one in five women engaged
      in these recent sexual risk behaviors. Simultaneous logistic regression results
      revealed IPV-related PTSD, but not drug or alcohol problems, was significantly
      associated with sexual risk behavior while controlling for childhood abuse and
      demographic covariates. Women with IPV-related PTSD had four times greater odds
      of recent sexual risk behavior compared to women without IPV-related PTSD.
      Implications for HIV prevention interventions are discussed.

PMID- 19856096
TI  - Neurofeedback for autistic spectrum disorder: a review of the literature.
AB  - There is a need for effective interventions to address the core symptoms and
      problems associated with autistic spectrum disorder (ASD). Behavior therapy
      improves communication and behavioral functioning. Additional treatment options
      include psychopharmacological and biomedical interventions. Although these
      approaches help children with autistic problems, they may be associated with side
      effects, risks or require ongoing or long-term treatment. Neurofeedback is a
      noninvasive approach shown to enhance neuroregulation and metabolic function in
      ASD. We present a review of the literature on the application of Neurofeedback to
      the multiple problems associated with ASD. Directions for future research are
      discussed.

PMID- 19856094
TI  - Pronuclear formation of freeze-dried canine spermatozoa microinjected into mouse
      oocytes.
AB  - PURPOSE: The aim of the present study was to investigate the fertilizing capacity
      of fresh, frozen-thawed and freeze-dried canine spermatozoa. METHODS: After
      canine spermatozoa were injected into mouse oocytes, the rates of oocyte
      activation, male pronuclear formation and chromosomal aberrations were
      investigated. RESULTS: The rates of oocyte activation were comparable (90.6
      100%), no matter the sperm type injected. The percentage of male pronuclear
      formation was higher (P < 0.001) in the freeze-dried spermatozoa (92.3%) than the
      fresh (61.5%) and frozen-thawed (69.2%) spermatozoa. However, the chromosomal
      damage in the oocytes injected with freeze-dried spermatozoa was higher (72.9%: P
      < 0.001) than with fresh (26.9%) and frozen-thawed (21.4%) spermatozoa.
      CONCLUSIONS: These data indicate using mouse oocytes that freeze-dried canine
      spermatozoa may potentially fertilize canine oocytes although chromosomal damage
      is frequently generated.

PMID- 19856097
TI  - Mutation screening of breast cancer susceptibility genes in Chinese high-risk
      families: the results will develop the genetic testing strategy in China.

PMID- 19856098
TI  - Genetic variants in GSTM3 gene within GSTM4-GSTM2-GSTM1-GSTM5-GSTM3 cluster
      influence breast cancer susceptibility depending on GSTM1.
AB  - Mu class of Glutathione-S-transferase (GSTM) genes arrange in a tandem on
      chromosome 1p13.3. The relationship between genetic variants in the GSTM1-5 gene
      cluster and breast cancer is still ambiguous. In the present study, 17 tagging
      single-nucleotide polymorphisms (SNPs) covering the GSTMs cluster were originally
      selected and 11 validated SNPs were used for genotyping 921 cases and 711
      controls. The association analyses were performed according to the absence or
      presence of GSTM1. In the GSTM1-/- group, the allele frequency of one SNP in
      GSTM3 was significantly different between cases and controls (P = 2.0 x 10(-4),
      corrected P = 0.001), with odds ratio of 1.75 (95% confidence interval, 1.26
      2.44). The observed association in the GSTM1-/- group was successfully replicated
      in an independent population set (familial/early-onset breast cancer cases, n =
      267; community-based controls, n = 667). The combined P values were robust (10(
      6)) and the false positive report probability (FPRP) values were low. In
      contrast, no susceptibility allele/haplotype was identified when the GSTM1 gene
      was present. Based on epidemiological observations, we further identified two
      genetic variants in the GSTM3 locus accounting for differential expression of
      GSTM3 in normal breast tissues by such means as altering binding of RNA-pol-II.
      Protective genotypes were correlated with higher GSTM3 expression levels. In
      conclusion, SNPs/haplotypes in the GSTM3 gene within the GSTMs gene cluster are
      likely to contribute to breast cancer risk when the GSTM1 is absent. We infer
      that GSTM3 catalyzing ability in normal breast tissue might protect against
      breast carcinogenesis.

PMID- 19856099
TI  - Nucleoside map of the human central nervous system.
AB  - Nucleosides are neuromodulators that have a wide range of biological roles in the
      brain. In order to better understand the function of nucleosides in the human
      central nervous system (CNS), we constructed a nucleoside map showing the
      concentration of various nucleosides and their metabolites using post mortem
      samples from 61 human brain areas and 4 spinal cord areas. We evaluated in vivo
      tissue levels of four nucleosides (uridine, inosine, guanosine, and adenosine)
      and three of their metabolites (uracil, hypoxanthine, and xanthine). The
      concentrations of nucleosides were unevenly distributed across different brain
      regions, where the highest levels were found in the cerebral cortex and basal
      ganglia, whereas the lowest concentrations were located in the locus coeruleus,
      the zona incerta, the substantia nigra, and the inferior colliculus. The regional
      differences in nucleoside levels in the CNS may reflect the distinct
      physiological functions adopted by these compounds in different brain areas.

PMID- 19856101
TI  - Long-term repopulation effects of donor BMDCs on intestinal epithelium.
AB  - BACKGROUND: Bone marrow-derived cells (BMDCs) have the ability to differentiate
      into intestinal epithelial cells after transplantation and participate in the
      regeneration process of damaged epithelium. AIMS: To investigate whether BMDCs
      could differentiate into intestinal epithelium long term in chimeric mice after
      transplantation and without special treatment. METHODS: Forty irradiated C57BL/6
      mice were used. Thirty of them (group A) received transplantation of BMDCs from
      GFP transgenic mice, and ten (group B) received PBS. The chimeric percentage at
      the 14th month was examined by flow cytometry. Engraftment of BMDCs was detected
      by immunohistochemistry in intestinal epithelium. Immunofluorescence observation
      was used to detect coexpression of PCK, CD45 and Chromogranin A with GFP. BMDCs
      in the epithelium were observed by an immune electron microscope. The percent of
      GFP(+) epithelial cells was also determined by flow cytometry. RESULTS: Mice in
      group A had a survival rate of 93.3% 1 week after transplantation. BMDCs could
      engraft into recipients' intestinal epithelium. These cells expressed epithelial
      cell marker PCK, but could not express CD45. Some of them differentiated into
      enteroendocrine cells expressing Chromogranin A. GFP(+) villous epithelial cells
      ranged from 9.41 to 16.07% in different subgroups of group A. BMDCs in epithelium
      developed the characteristics of enterocytes and goblet cells. GFP(+)/PCK(+)
      epithelial cells at the 6th month made up a proportion of 16.11% among all the
      isolated epithelial cells. CONCLUSIONS: Long term, BMDCs could repopulate
      recipient's intestinal epithelium even without any special treatment, which
      suggests a novel insight into the maintenance of the intestinal epithelial
      constitution.

PMID- 19856100
TI  - Brain tumor stem cells.
AB  - Primary malignant brain cancer, one of the most deadly diseases, has a high rate
      of recurrence after treatment. Studies in the past several years have led to the
      hypothesis that the root of the recurrence may be brain tumor stem cells (BTSCs),
      stem-like subpopulation of cells that are responsible for propagating the tumor.
      Current treatments combining surgery and chemoradiotherapy could not eliminate
      BTSCs because these cells are highly infiltrative and possess several properties
      that can reduce the damages caused by radiation or anti-cancer drugs. BTSCs are
      similar to NSCs in molecular marker expression and multi-lineage differentiation
      potential. Genetic analyses of Drosophila CNS neoplasia, mouse glioma models, and
      human glioma tissues have revealed a link between increased NSC self-renewal and
      brain tumorigenesis. Furthermore, data from various rodent models of malignant
      brain tumors have provided compelling evidence that multipotent NSCs and lineage
      restricted neural progenitor cells (NPCs) could be the cell origin of brain
      tumors. Thus, the first event of brain tumorigenesis might be the occurrence of
      oncogenic mutations in the stem cell self-renewal pathway in an NSC or NPC. These
      mutations convert the NSC or NPC to a BTSC, which then initiates and sustains the
      growth of the tumor. The self-renewal of BTSCs is controlled by several
      evolutionarily conserved signaling pathways and requires an intact vascular
      niche. Targeting these pathways and the vascular niche could be a principle in
      novel brain tumor therapies aimed to eliminate BTSCs.

PMID- 19856102
TI  - Highly purified eicosapentaenoic acid ethyl ester prevents development of
      steatosis and hepatic fibrosis in rats.
AB  - BACKGROUND AND AIMS: Pathogenesis of nonalcoholic steatohepatitis (NASH) is
      considered to be involved in fat accumulation, oxidative stress, inflammation,
      and fibrosis in liver, but no drug therapy has been established as yet.
      Eicosapentaenoic acid (EPA) is an agent used clinically to treat
      hypertriglyceridemia, and has been reported to suppress reactive oxygen species
      and inflammation. Here, we aimed to assess the effect of EPA on progression of
      hepatic fibrosis in an animal model of NASH. METHODS: Wistar rats were fed a
      methionine- and choline-deficient (MCD) diet and given EPA ethyl ester (EPA-E)
      (1,000 mg/kg/day) or vehicle by gavage for 8 or 20 weeks. RESULTS: The MCD diet
      caused development of hepatic fibrosis and nodule formation at 20 weeks. EPA-E
      treatment significantly suppressed MCD-induced increase in fibrosis and hepatic
      hydroxyproline, and inhibited nodule formation. EPA-E treatment also decreased
      hepatic transforming growth factor (TGF)-beta1, and messenger RNA (mRNA) levels
      of connective tissue growth factor. EPA-E suppressed MCD-induced elevation of
      serum levels of ferritin, 8-isoprostane, soluble tumor necrosis factor receptor 1
      (sTNFR1), and sTNFR2 at 20 weeks, and hepatic triglyceride accumulation at 8
      weeks. CONCLUSIONS: EPA-E prevents progression of hepatic fibrosis in an MCD
      induced NASH model with reduction of oxidative stress, inflammation, and initial
      hepatic steatosis. Thus, EPA-E treatment may be a potential therapy to treat
      NASH.

PMID- 19856103
TI  - Sirolimus attenuates reduced-size liver ischemia-reperfusion injury but impairs
      liver regeneration in rats.
AB  - BACKGROUND: Evidence has suggested that immunosuppressive drugs impact ischemia
      reperfusion injury. AIMS: The purpose of the present study was to evaluate the
      effect of sirolimus on hepatic injury and regeneration in a rat reduced-size
      liver ischemia-reperfusion model. METHODS: Using a newly developed rat reduced
      size liver ischemia-reperfusion injury model, the effects of sirolimus were
      evaluated by assessing liver cell apoptosis and aspartate aminotransferase,
      myeloperoxidase, and malondialdehyde levels. In addition, liver regeneration
      after sirolimus treatment was evaluated by measuring liver weight resumption and
      by the histological examination of bromodeoxyuridine and proliferating cell
      nuclear antigen expression. RESULTS: Sirolimus significantly decreased liver cell
      apoptosis as well as tissue myeloperoxidase and malondialdehyde levels, but
      impaired postischemic liver regeneration. Ischemia-reperfusion-induced elevation
      of aspartate aminotransferase serum levels was significantly decreased by
      sirolimus. CONCLUSIONS: Despite an impairment of postischemic liver
      proliferation, sirolimus demonstrated beneficial amelioration of ischemia
      reperfusion-induced liver injury in a reduced-size liver model in rats.

PMID- 19856104
TI  - Inhibition of nuclear factor kappa B transcription activity drives a synergistic
      effect of pyrrolidine dithiocarbamate and cisplatin for treatment of renal cell
      carcinoma.
AB  - One of the impeding factors in the effective treatment of metastatic renal cell
      carcinoma (RCC) is their intrinsic and acquired resistance to chemotherapeutics.
      Many studies have shown that drug resistance, at least in part, is mediated by
      the upregulation of anti-apoptotic (Bcl-2) and multidrug resistance molecules
      (MDR-1 and MRP-1) by the transcription factor nuclear factor kappa B (NF-kappaB).
      Combining NF-kappaB inhibitors with conventional chemotherapeutics could overcome
      resistance of cancer cells. In this study, we examined the synergistic effect of
      pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, and cisplatin, on two
      human metastatic RCC cell lines ACHN and SN12K1. Individual non-toxic
      concentrations of PDTC and cisplatin, when combined, synergistically induced a
      significant increase in apoptosis of the two RCC cell lines. In ACHN cells, the
      groups with nuclear translocation of NF-kappaB showed resistance to apoptosis,
      but in SN12K1 cells, the groups with NF-kappaB translocation were susceptible to
      apoptosis. The combination treatment significantly decreased the transcription
      activity of all NF-kappaB subunits in both cell lines. Anti-apoptotic proteins
      Bcl-2 and Bcl-(XL) were significantly decreased in the combination therapy group
      of both cell lines, but MDR-1 was decreased only in the ACHN cells. No changes in
      MRP-1 were observed in any of the treatment groups. The results demonstrate the
      potential of PDTC to be an adjunct therapeutic agent. The major mechanism of the
      synergistic effect appears to be mediated by the inhibition of transcription
      activity of NF-kappaB rather than its expression, and the resultant decrease in
      the anti-apoptotic proteins Bcl-2 and Bcl-(XL).

PMID- 19856105
TI  - Involvement of tyrosine phosphatase CD45 in apoptosis.
AB  - CD45 is a transmembrane molecule with phosphatase activity expressed in all
      nucleated haematopoietic cells and plays a major role in immune cells. It is a
      protein tyrosine phosphatase that is essential for antigen-receptor-mediated
      signal transduction by regulating Src family members that initiate TCR signaling.
      CD45 is being attributed a new emerging role as an apoptosis regulator. Cross
      linking of the extracellular portion of the CD45 by monoclonal antibodies and by
      galectin-1, can induce apoptosis in T and B cells. Interestingly, this
      phosphatase has also been involved in nuclear apoptosis induced by mitochondrial
      perturbing agents. Furthermore, it is involved in apoptosis induced by HIV-1.
      CD45 defect is implicated in various diseases such as severe-combined
      immunodeficiency disease (SCID), acquired immunodeficiency syndrome (AIDS),
      lymphoma and multiple myelomas. The understanding of the mechanisms by which CD45
      regulates apoptosis would be very useful in disease treatment.

PMID- 19856106
TI  - Creativity as openness: improvising health and care 'situations'.
AB  - Creativity has become an oft-used word in UK public policy, but perhaps it is
      also under-imagined. This paper contends that there is an instrumental tendency
      to narrowly frame creativity as innovation, implying a reproducible product,
      instead of more openly as improvisation, a situational, embodied and temporal
      process. This is not a simple dichotomy (innovation and improvisation, product
      and process, can be mutually informing concepts), nor is it specifically a
      question of definition; rather, it relates to an ontological orientation, and
      related to that are issues of epistemological implications. In particular the
      paper is concerned with the value of the arts in public policy, as situated in
      the social, and therefore human, spaces of health and care; and more generally
      the arts in society. The paper brings together a broad discussion from across
      disciplines, not in an interdisciplinary attempt to solve a problem, or to be
      reductive in the analysis, but to begin to approach a reorienting of
      understandings of creativity and the human value and foundation of the arts in
      society.

PMID- 19856107
TI  - Enhanced oral bioavailability of griseofulvin via niosomes.
AB  - The aim of the present report was to develop nonionic surfactant vesicles
      (niosomes) to improve poor and variable oral bioavailability of griseofulvin.
      Niosomes were prepared by using different nonionic surfactants span 20, span 40,
      and span 60. The lipid mixture consisted of surfactant, cholesterol, and dicetyl
      phosphate in the molar ratio of 125:25:1.5, 100:50:1.5, and 75:75:1.5,
      respectively. The niosomal formulations were prepared by thin film method and
      ether injection method. The influence of different formulation variables such as
      surfactant type, surfactant concentration, and cholesterol concentration was
      optimized for size distribution and entrapment efficiency for both methods.
      Result indicated that the niosomes prepared by thin film method with span 60
      provided higher entrapment efficiency. The niosomal formulation exhibited
      significantly retarded in vitro release as compared with free drug. The in vivo
      study revealed that the niosomal dispersion significantly improved the oral
      bioavailability of griseofulvin in albino rats after a single oral dose. The
      maximum concentration (Cmax) achieved in case of niosomal formulation was
      approximately double (2.98 microg/ml) as compared to free drug (1.54 microg/ml).
      Plasma drug profile also suggested that the developed niosomal system also has
      the potential of maintaining therapeutic level of griseofulvin for a longer
      period of time as compared to free griseofulvin. The niosomal formulation showed
      significant increase in area under the curve0-24 (AUC; 41.56 microg/ml h) as
      compared to free griseofulvin (22.36 microg/ml h) reflecting sustained release
      characteristics. In conclusion, the niosomal formulation could be one of the
      promising delivery system for griseofulvin with improved oral bioavailability and
      prolonged drug release profiles.

PMID- 19856108
TI  - Encapsulation of ketoprofen and ketoprofen lysinate by prilling for controlled
      drug release.
AB  - In this paper, ketoprofen and ketoprofen lysinate were used as model drugs in
      order to investigate release profiles of poorly soluble and very soluble drug
      from sodium alginate beads manufactured by prilling. The effect of polymer
      concentration, viscosity, and drug/polymer ratio on bead micromeritics and drug
      release rate was studied. Ketoprofen and ketoprofen lysinate loaded alginate
      beads were obtained in a very narrow dimensional range when the Cross model was
      used to set prilling operative conditions. Size distribution of alginate beads in
      the hydrated state was strongly dependent on viscosity of drug/polymer solutions
      and frequency of the vibration. The release kinetics of the drugs showed that
      drug release rate was related with alginate concentration and solubility of the
      drug. Alginate solutions with concentration higher than 0.50% (w/w) were suitable
      to prepare ketoprofen gastro-resistant formulation, while for ketoprofen lysinate
      alginate, concentration should be increased to 1.50% (w/w) in order to retain the
      drug in gastric environment. Differential scanning calorimetry thermograms and
      Fourier transform infrared analyses of drug-loaded alginate beads indicated
      complex chemical interactions between carboxyl groups of the drug and polymer
      matrix in drug-loaded beads that contribute to the differences in release profile
      between ketoprofen and ketoprofen lysinate. Total release of the drugs in
      intestinal medium was dependent on the solubility of the drug and was achieved
      between 4 and 6 h.

PMID- 19856110
TI  - For lack of a better plan: a framework for ethical, legal, and clinical
      challenges in complex inpatient discharge planning.
AB  - This article proposes a new theoretical framework for analyzing complex inpatient
      hospital discharge dilemmas. Each component of the framework is defined,
      illustrated with a hypothetical case, and discussed from legal,ethical and
      practical problem solving viewpoints. Patients who lack reasonable and safe
      discharge plans invariably challenge existing interpretations of autonomy,
      capacity, and justice. Such cases often require legal advice and sometimes
      intervention from the judicial system when alternatives are exhausted. As an
      extension of previous work on discharge planning (Swidler et al., 2007), this
      work strives to provide medical professionals with an organized way of
      approaching inpatient discharge barriers and to encourage new ways of considering
      and designing healthcare policy both to reduce discharge delays and also better
      to serve patients.

PMID- 19856109
TI  - Biofield therapies: helpful or full of hype? A best evidence synthesis.
AB  - BACKGROUND: Biofield therapies (such as Reiki, therapeutic touch, and healing
      touch) are complementary medicine modalities that remain controversial and are
      utilized by a significant number of patients, with little information regarding
      their efficacy. PURPOSE: This systematic review examines 66 clinical studies with
      a variety of biofield therapies in different patient populations. METHOD: We
      conducted a quality assessment as well as a best evidence synthesis approach to
      examine evidence for biofield therapies in relevant outcomes for different
      clinical populations. RESULTS: Studies overall are of medium quality, and
      generally meet minimum standards for validity of inferences. Biofield therapies
      show strong evidence for reducing pain intensity in pain populations, and
      moderate evidence for reducing pain intensity hospitalized and cancer
      populations. There is moderate evidence for decreasing negative behavioral
      symptoms in dementia and moderate evidence for decreasing anxiety for
      hospitalized populations. There is equivocal evidence for biofield therapies'
      effects on fatigue and quality of life for cancer patients, as well as for
      comprehensive pain outcomes and affect in pain patients, and for decreasing
      anxiety in cardiovascular patients. CONCLUSION: There is a need for further high
      quality studies in this area. Implications and future research directions are
      discussed.

PMID- 19856111
TI  - Communication and conflict management training for clinical bioethics committees.

PMID- 19856112
TI  - Patient-centered care and cultural practices: process and criteria for evaluating
      adaptations of norms and standards in health care institutions.
AB  - It is widely recognized that health care providers and health care organizations
      need to take into account the cultural frameworks of patients.Such an orientation
      is consistent with patient-centered care that focuses on the particularity of
      individual patients (Stewart, 2001). In a patient-centered approach clinicians
      individualize the care they provide to each patient, and seek to develop and
      promote partnerships with patients. Eliciting and engaging a patient's cultural
      values and perspectives is a key component of patient-centered care. An important
      body of scholarship has developed around the question of how attending to the
      needs of culturally diverse patient populations should affect the provision of
      clinical care and other health services (Betan court, 2004). This discussion has
      led to many practical changes in how health care providers are trained. Today,
      educational programs in faculties of medicine, schools of nursing and schools of
      allied health incorporate cultural competence training in their curricula.Despite
      the increased focus in education and clinical practice on providing patient
      centered and culturally sensitive care, challenging situations can arise when
      patients wish to perform practices that do not fit within institutional or
      clinical norms. In many such situations, health care providers and hospital
      administrators adapt institutional or clinical norms and structures. In other
      cases it may be difficult to decide whether particular adaptations should be made
      or not. Such scenarios may be sources of important concern and stress for
      patients, families and health care providers. The assessment of a given situation
      is rendered more complex when the adaptation being considered has the potential
      to infringe on the rights of others (such as other patients,visitors to the
      hospital, or health care providers). In this paper, I propose a328 HEC Forum
      (2009) 21(4): 327- 339 process, including four evaluative criteria, for assessing
      such scenarios. This discussion is also relevant for considering practices that
      require adaptation of institutional or clinical norms, but which are not based in
      a specific cultural or religious framework. Given a commitment to respect
      autonomy,administrators and clinicians should also carefully consider requests
      for adaptation which patients associate with their own core beliefs and deeply
      held commitments.

PMID- 19856113
TI  - Conscience and conscientious objection of health care professionals refocusing
      the issue.

PMID- 19856115
TI  - Quinoline biodegradation and its nitrogen transformation pathway by a Pseudomonas
      sp. strain.
AB  - A Pseudomonas sp. strain, which can utilize quinoline as its sole carbon,
      nitrogen and energy source, was isolated from activated sludge in a coking
      wastewater treatment plant. Quinoline can be degraded via the 8-hydroxycoumarin
      pathway. We quantified the first two organic intermediates of the biodegradation,
      2-hydroxyquinoline and 2,8-dihydroxyquinoline. We tracked the transformation of
      the nitrogen in quinoline in two media containing different C/N ratios. At least
      40.4% of the nitrogen was finally transformed into ammonium when quinoline was
      the sole C and N source. But addition of an external carbon source like glucose
      promoted the transformation of N from NH3 into NO3(-), NO2(-), and then to N2.
      The product analysis and gene characteristics indicated that the isolate
      accomplished heterotrophic nitrification and aerobic denitrification
      simultaneously. The study also demonstrated that quinoline and its metabolic
      products can be eliminated if the C/N ratio is properly controlled in the
      treatment of quinoline-containing wastewater.

PMID- 19856114
TI  - Structural and expressional analysis of the B-hordein genes in Tibetan hull-less
      barley.
AB  - The B-hordein gene family was analyzed from two Tibetan hull-less barley
      cultivars Z09 and Z26 (Hordeum vulgare subsp. vulgare). Fourteen B-hordein genes,
      designated BZ09-2 to BZ09-5 (from Z09) and BZ26-1 to BZ26-10 (from Z26), were
      sequenced. Seven of them, similar to a previously reported BZ09-1 from Z09, were
      predicted to encode putative active proteins each with a signal peptide, a
      repetitive domain, and a C-terminal region; seven of them were predicted to be
      pseudogenes. The B-hordein gene family was analyzed using all known
      representatives of B-hordein sequences and two most similar LMW-GSs of Triticum
      aestivum. Alignment of these seven putative proteins with known B-hordeins and
      two most similar LMW-GSs of T. aestivum revealed that they shared a common motif.
      A large variation was observed between numbers of repeat units of predicted B
      hordeins of Z26 and Z09. Phylogenetic analysis revealed that all BZ26 clones were
      clustered in a subgroup, and BZ09-1 formed another subgroup by itself in the
      putative eight active genes. In addition, six 5'-upstream regulatory sequences of
      the B-hordein genes were isolated from the two accessions by a single
      oligonucleotide nested PCR, and several different mutations were identified in
      the cis-acting element GLM and two distinctive sequences (Z09P-2 and Z26P-3).
      Phylogenetic analysis of 5'-upstream regulatory regions of the B-hordein genes
      showed that members from the same accession were clustered together except for
      two distinct members. Quantitative real time PCR analysis indicated distinct
      expression levels of B-hordein genes in four developing stages of developing
      grains in two accessions. These findings suggest B-hordein genes have intrinsic
      differences between accessions, and this knowledge will be useful for
      incorporating the B-hordeins protein in barley breeding programs.

PMID- 19856117
TI  - Serum calcium levels are elevated among women with untreated postmenopausal
      breast cancer.
AB  - OBJECTIVE: Reports of an association between primary hyperparathyroidism in women
      and risk of breast cancer suggest an etiologic role for high serum calcium.
      However, data on the association between serum calcium levels and breast cancer
      in women without clinical hyperparathyroidism are limited. METHODS: We conducted
      a hospital-based case-control study among postmenopausal women in Fargo, ND.
      Cases were women aged 65 and older with newly diagnosed, histologically confirmed
      breast cancer. Controls were aged 65 and older without clinical cancer who were
      seen at the same hospital. RESULTS: We obtained data on 190 white cases and 172
      white controls. Primary hyperparathyroidism (an abnormally high calcium level
      confirmed by an abnormally high serum PTH) was found in 3/190 cases and in 0/172
      controls (p = 0.25). After excluding the women with primary hyperparathyroidism,
      the mean calcium levels among cases was 9.6 mg/dL (range, 7.5-11.0, SD = 0.47)
      vs. 9.4 mg/dL (7.7-10.5, 0.43) among the controls (p < 0.0001). Comparing women
      in the top with women in the bottom tertile of serum calcium, the multivariable
      adjusted odds ratio (OR) for breast cancer was 5.21 (95% CI: 2.59-10.48). There
      was no relationship between serum calcium and tumor size or stage. CONCLUSION:
      The distribution of serum calcium levels among postmenopausal women with incident
      breast cancer was shifted significantly toward the right. These findings are
      consistent with an effect of early breast tumors on calcium homeostasis. However,
      the lack of association between serum calcium levels and tumor size or stage
      supports the hypothesis that subclinical hyperparathyroidism may increase the
      risk for breast cancer.

PMID- 19856118
TI  - Citrus fruit and cancer risk in a network of case-control studies.
AB  - BACKGROUND: Citrus fruit has shown a favorable effect against various cancers. To
      better understand their role in cancer risk, we analyzed data from a series of
      case-control studies conducted in Italy and Switzerland. PATIENTS AND METHODS:
      The studies included 955 patients with oral and pharyngeal cancer, 395 with
      esophageal, 999 with stomach, 3,634 with large bowel, 527 with laryngeal, 2,900
      with breast, 454 with endometrial, 1,031 with ovarian, 1,294 with prostate, and
      767 with renal cell cancer. All cancers were incident and histologically
      confirmed. Controls were admitted to the same network of hospitals for acute,
      nonneoplastic conditions. Odds ratios (OR) were estimated by multiple logistic
      regression models, including terms for major identified confounding factors for
      each cancer site, and energy intake. RESULTS: The ORs for the highest versus
      lowest category of citrus fruit consumption were 0.47 (95% confidence interval,
      CI, 0.36-0.61) for oral and pharyngeal, 0.42 (95% CI, 0.25-0.70) for esophageal,
      0.69 (95% CI, 0.52-0.92) for stomach, 0.82 (95% CI, 0.72-0.93) for colorectal,
      and 0.55 (95% CI, 0.37-0.83) for laryngeal cancer. No consistent association was
      found with breast, endometrial, ovarian, prostate, and renal cell cancer.
      CONCLUSIONS: Our findings indicate that citrus fruit has a protective role
      against cancers of the digestive and upper respiratory tract.

PMID- 19856119
TI  - Spatial regulation and organization of DNA replication within the nucleus.
AB  - Duplication of chromosomal DNA is a temporally and spatially regulated process.
      The timing of DNA replication initiation at various origins is highly
      coordinated; some origins fire early and others late during S phase. Moreover,
      inside the nuclei, the bulk of DNA replication is physically organized in
      replication factories, consisting of DNA polymerases and other replication
      proteins. In this review article, we discuss how DNA replication is organized and
      regulated spatially within the nucleus and how this spatial organization is
      linked to temporal regulation. We focus on DNA replication in budding yeast and
      fission yeast and, where applicable, compare yeast DNA replication with that in
      bacteria and metazoans.

PMID- 19856120
TI  - Metal exposure and effects in voles and small birds near a mining haul road in
      Cape Krusenstern National Monument, Alaska.
AB  - Voles and small passerine birds were live-captured near the Delong Mountain
      Regional Transportation System (DMTS) haul road in Cape Krusenstern National
      Monument in northwest Alaska to assess metals exposure and sub-lethal biological
      effects. Similar numbers of animals were captured from a reference site in
      southern Cape Krusenstern National Monument for comparison. Histopathological
      examination of selected organs, and analysis of cadmium, lead, and zinc
      concentrations in liver and blood samples were performed. Voles and small birds
      captured from near the haul road had about 20 times greater blood and liver lead
      concentrations and about three times greater cadmium concentrations when compared
      to those from the reference site, but there were no differences in zinc tissue
      concentrations. One vole had moderate metastatic mineralization of kidney tissue,
      otherwise we observed no abnormalities in internal organs or DNA damage in the
      blood of any of the animals. The affected vole also had the greatest liver and
      blood Cd concentration, indicating that the lesion might have been caused by Cd
      exposure. Blood and liver lead concentrations in animals captured near the haul
      road were below concentrations that have been associated with adverse biological
      effects in other studies; however, subtle effects resulting from lead exposure,
      such as the suppression of the activity of certain enzymes, cannot be ruled out
      for some individual animals. Results from our 2006 reconnaissance-level study
      indicate that overall, voles and small birds obtained from near the DMTS road in
      Cape Krusenstern National Monument were not adversely affected by metals
      exposure; however, because of the small sample size and other uncertainties,
      continued monitoring of lead and cadmium in terrestrial habitats near the DMTS
      road is advised.

PMID- 19856121
TI  - Study of harmful algal blooms in a eutrophic pond, Bangladesh.
AB  - The purpose of this research was to analyze the underlying mechanisms and
      contributing factors related to the seasonal dynamic of harmful algal blooms in a
      shallow eutrophic pond, Bangladesh during September 2005-July 2006. Two
      conspicuous events were noted simultaneously throughout the study period: high
      concentration of phosphate-phosphorus (>3.03; SD 1.29 mg l(-1)) and permanent
      cyanobacterial blooms {>3,981.88*10(3) cells l(-1) (SD 508.73)}. Cyanobacterial
      blooms were characterized by three abundance phases, each of which was associated
      with different ecological processes. High nitrate-nitrogen (>2.35; SD 0.83 mg l(
      1)), for example, was associated with high cyanobacterial abundance, while low
      nitrate-nitrogen (0.36; SD 0.2 mg l(-1)) was recorded during moderate abundance
      phase. Extremely low NO3-N/PO4-P ratio (>3.55, SD 2.31) was recorded, and all
      blooming taxa were negatively correlated with this ratio. Cyanobacterial blooms
      were positively correlated with temperature (r=0.345) and pH (0.833; p=0.05) and
      negatively correlated with transparency (r=-0.956; p=0.01). Although Anabaena
      showed similar relationship with water quality parameters as cyanobacteria, the
      co-dominant Microcystis exhibited negative relationship with temperature (r=
      0.386) and nitrate-nitrogen (r=-0.172). This was attributed to excessive growth
      of Anabaena that suppressed Microcystis's growth. Planktothrix was the third most
      dominant taxa, while Euglena was regarded as opportunistic.

PMID- 19856122
TI  - Assessment of trace metal concentration in feathers of seabird (Larus
      dominicanus) sampled in the Florianopolis, SC, Brazilian coast.
AB  - Cd, Co, Cr, Cu, Mn, Ni, Zn, and Pb were measured in feather samples of adult,
      subadult, and juvenile of Larus dominicanus, sampled in the Florianolis, SC, in
      the south of Brazil in December 2005, by flame atomic absorption
      spectrophotometry. The average of the distribution of Cd concentration in adult
      feathers (0.072 microg g(-1)) was significantly different than that found in
      juvenile feathers (0.021 microg g(-1)). Cu concentration averages were not
      significantly different between adults (13.30 microg g(-1)), subadults (9.67
      microg g(-1)), and juveniles (13.76 microg g(-1)). For adults and juveniles there
      was significant difference in feather concentrations for Cd, Co, Cr, Ni, and Pb.
      The distribution of Mn concentration averages in feathers differs between adults
      (11.36 microg g(-1)) and juveniles (1.184 microg g(-1)). Ni concentration
      averages of adults (5.92 microg g(-1)) were significantly higher than those of
      juveniles (2.23 microg g(-1)). For Pb, concentration averages were significantly
      higher in adults (7.53 microg g(-1)) than in juveniles (1.47 microg g(-1)). The
      concentration of Co and Cr in juvenile and subadults are statistically different
      when compared with the adults. In the present study, levels of Cd, Co, Cr, Mn,
      Ni, Zn, and Pb increased with age. The concentrations of essential trace elements
      in L. dominicanus were generally comparable to values reported in other studies.
      With non-essential metals (Cd, Pb, and Ni), in our study, L. dominicanus had
      lower values than those reported for their northern Atlantic counterparts.

PMID- 19856123
TI  - An assessment of selected trace elements in intertidal surface sediments
      collected from the Peninsular Malaysia.
AB  - Concentrations of 11 trace elements (V, Cr, Co, Ni, Cu, Zn, As, Ag, Cd, Pb, and
      U) were determined in the intertidal surface sediments of Peninsular Malaysia.
      The average trace element concentrations are ranked as follows:
      Zn>V>As>Cr>Pb>Cu>Ni>Co>U>g>Cd. Interim Sediment Quality Guidelines (ISQGs)
      employed in present study are the Australia and New Zealand joint guideline
      (ANZECC/ARMCANZ), and the Hong Kong authorities. From the pooled data, none of
      these trace elements have the average concentration above the ISQG-high values.
      However, As and Ag average concentrations were over the ISQG-low values. Some
      elements were found to have the average concentration above the ISQG-high and/or
      ISQG-low in certain locations, including Kampung Pasir Putih (JPP), Lumut Port
      (ALP), Kuala Perai (PKP), Port Dickson (NPD), and others. The lowest and highest
      concentrations in a specific sampling location and maritime area varied among the
      elements, variations that were greatly affected by natural and anthropogenic
      activities in a given area. For each trace element, there were various levels of
      concentration among the sampling locations and maritime areas. These patterns
      indicated pollutant sources of an element for each area perhaps derived from
      nearby areas and did not widely distributed to other locations. It is necessary
      for Malaysia to develop an ISQG for effective quick screening and evaluation of
      the coastal environment of Peninsular Malaysia.

PMID- 19856124
TI  - What we see and don't see when we look at 'competence':  notes on a god term.

PMID- 19856125
TI  - Expression of mRNA for 3HADH in manipulated embryos to produce germline chimeric
      chickens.
AB  - Germline chimeric chickens were produced by the transfer of primordial germ cells
      (PGCs) or blastoderm cells. The hatchability of eggs produced by transfer of
      exogenous PGCs is usually low. The purpose of the present study was investigated
      to express (3-hydroxyacyl CoA dehydrogenase) 3HADH which is a limiting enzyme in
      the beta-oxidation of fatty acids for hatching energy. Manipulations of both
      donor and recipient eggshells were as follows. A window approximately 10 mm in
      diameter was opened at the pointed end of the eggs at stage 12-15 days
      incubation. Donor PGCs, taken from the blood vessels of donor embryos from
      fertilized eggs at the same stage of development, were injected into the blood
      vessels of recipient embryos. The muscles of chicks in the eggs with transferred
      PGCs were removed after 20 days of incubation. A cDNA was prepared from the total
      RNA. The expression of 3HADH in the manipulated embryos was investigated using
      real-time PCR analysis. Real-time PCR analysis showed that expression of 3HADH
      was reduced in the muscles of manipulated embryos.

PMID- 19856126
TI  - No need for an "expiry date" in chronic peritoneal dialysis to prevent
      encapsulating peritoneal sclerosis.

PMID- 19856127
TI  - RFT1-CDG: deafness as a novel feature of congenital disorders of glycosylation.
AB  - Congenital disorders of glycosylation (CDG) are genetic diseases due to defects
      in the synthesis of glycans and in the attachment of glycans to lipids and
      proteins. Actually, some 42 CDG are known including defects in protein N
      glycosylation, in protein O-glycosylation, in lipid glycosylation, and in
      multiple and other glycosylation pathways. Most CDG are multisystem diseases and
      a large number of signs and symptoms have already been reported in CDG. An
      exception to this is deafness. This symptom has not been observed as a consistent
      feature in CDG. In 2008, a novel defect was identified in protein N
      glycosylation, namely in RFT1. This is a defect in the assembly of N-glycans.
      RFT1 is involved in the transfer of Man(5)GlcNAc(2)-PP-Dol from the cytoplasmic
      to the luminal side of the endoplasmic reticulum. According to the novel
      nomenclature (non-italicized gene symbol followed by -CDG) this defect is named
      RFT1-CDG. Recently, three other patients with RFT1-CDG have been reported and
      here we report two novel patients. Remarkably, all six patients with RFT1-CDG
      show sensorineural deafness as part of a severe neurological syndrome. We
      conclude that RFT1-CDG is the first 'deafness-CDG'. CDG should be included in the
      work-up of congenital, particularly syndromic, hearing loss.

PMID- 19856128
TI  - Same question, different answers: a comparison of global health assessments using
      visual analogue scales.
AB  - PURPOSE: To compare responses to two global health VAS of patients with
      rheumatoid arthritis at the same assessment within the same questionnaire.
      METHODS: Secondary analysis of randomised controlled trial data. Patients
      completed the patient global assessment VAS (PG-VAS) (horizontal 10 cm scale,
      left (0), right (100), no incremental markers) and EQ-5D-VAS (EQ-VAS) (vertical
      20 cm scale, 100 at the top, markers at each increment of 10). Both asked "how
      good or bad is your health today, in your opinion, from 100 'Best imaginable
      health state' to 0 'Worst imaginable health state'." Agreement was assessed using
      intra-class correlation co-efficients (ICC) and Bland-Altman plots. RESULTS: Four
      hundred and forty-eight patients reported median PG-VAS 66 (IQR 51, 77) and EQ
      VAS 65 (IQR 50, 80) scores. Correlation of the VAS scales was moderate at
      baseline (ICC 0.564) and longitudinally (ICC 0.503). Bland-Altman plots suggested
      poor concordance of the PG-VAS and EQ-VAS; the limits of agreement were +/-32.3
      on a 0-100 scale. PG-VAS scores were evenly distributed; EQ-VAS scores clustered
      at increments of 10; rounding did not improve agreement. CONCLUSIONS: The EQ-VAS
      and PG-VAS scores are not interchangeable at the individual level. The EQ-VAS
      correlated more strongly with disease-specific and health-related quality of life
      measures, therefore, appears preferable.

PMID- 19856129
TI  - Production of membrane proteins for NMR studies using the condensed single
      protein (cSPP) production system.
AB  - In the Single Protein Production (SPP) method, all E. coli cellular mRNAs are
      eliminated by the induction of MazF, an ACA-specific mRNA interferase. When an
      mRNA for a membrane protein, engineered to have no ACA sequences without altering
      its amino acid sequence, is induced in the MazF-induced cells, E. coli is
      converted into a bioreactor producing only the targeted membrane protein. Here we
      demonstrate that three prokaryotic inner membrane proteins, two prokaryotic outer
      membrane proteins, and one human virus membrane protein can be produced at very
      high levels, and assembled in appropriate membrane fractions. The condensed SPP
      (cSPP) system was used to selectively produce isotope-enriched membrane proteins
      for NMR studies in up to 150-fold condensed culture without affecting protein
      yields, providing more than 99% cost saving for isotopes. As a novel application
      of the cSPP system for studies of membrane proteins prior to purification we also
      demonstrate, for the first time, fast detergent screening by microcoil NMR and
      well-resolved NMR spectra of several targeted integral membrane proteins obtained
      without purification.

PMID- 19856130
TI  - Virtual prototyping study shows increased ATPase activity of Hsp90 to be the key
      determinant of cancer phenotype.
AB  - Hsp90 is an ATP-dependent molecular chaperone that regulates key signaling
      proteins and thereby impacts cell growth and development. Chaperone cycle of
      Hsp90 is regulated by ATP binding and hydrolysis through its intrinsic ATPase
      activities, which is in turn modulated by interaction with its co-chaperones.
      Hsp90 ATPase activity varies in different organisms and is known to be increased
      in tumor cells. In this study we have quantitatively analyzed the impact of
      increasing Hsp90 ATPase activity on the activities of its clients through a
      virtual prototyping technology, which comprises a dynamic model of Hsp90
      interaction with clients involved in proliferation pathways. Our studies
      highlight the importance of increased ATPase activity of Hsp90 in cancer cells as
      the key modulator for increased proliferation and survival. A tenfold increase in
      ATPase activity of Hsp90 often seen in cancer cells increases the levels of
      active client proteins such as Akt-1, Raf-1 and Cyclin D1 amongst others to about
      12-, 8- and 186-folds respectively. Additionally we studied the effect of a
      competitive inhibitor of Hsp90 activity on the reduction in the client protein
      levels. Virtual prototyping experiments corroborate with findings that the drug
      has almost 10- to 100-fold higher affinity as indicated by a lower IC(50) value
      (30-100 nM) in tumor cells with higher ATPase activity. The results also indicate
      a 15- to 25-fold higher efficacy of the inhibitor in reducing client levels in
      tumor cells. This analysis provides mechanistic insights into the links between
      increased Hsp90 ATPase activity, tumor phenotype and the hypersensitivity of
      tumor Hsp90 to inhibition by ATP analogs. ELECTRONIC SUPPLEMENTARY MATERIAL: The
      online version of this article (doi:10.1007/s11693-009-9046-3) contains
      supplementary material, which is available to authorized users.

PMID- 19856131
TI  - Backbone (1)H, (13)C, and (15)N NMR assignment for the inactive form of the
      retroviral protease of the murine intracisternal A-type particle, inMIA-14 PR.
AB  - Proteases play a crucial role in the retroviral infection but so far the
      mechanism of their regulation remains unclear. Protease MIA-14 from murine
      intracisternal A-type particles, containing a C-terminal domain rich in glycines
      (G-patch), is responsible for binding of single-stranded oligonucleotides (both
      RNA and DNA) without inhibiting the proteolytic activity. For investigations of
      untill now poorly characterized protease-oligonucleotide interactions,
      assignments of the observed NMR frequencies are mandatory. An almost complete
      assignments of the main chain and (13)C(beta) side chain resonances of the 34 kDa
      homo-dimeric inMIA-14 PR is presented in this study.

PMID- 19856132
TI  - The pivotal role of the beta 7 strand in the intersubunit contacts of different
      human small heat shock proteins.
AB  - Human alpha B-crystallin and small heat shock proteins HspB6 and HspB8 were
      mutated so that all endogenous Cys residues were replaced by Ser and the single
      Cys residue was inserted in a position homologous to that of Cys137 of human
      HspB1, i.e. in a position presumably located in the central part of beta 7 strand
      of the alpha-crystallin domain. The secondary, tertiary, and quaternary
      structures of thus obtained Cys-mutants as well as their chaperone-like activity
      were similar to those of their wild-type counterparts. Mild oxidation of Cys
      mutants leads to formation of disulfide bond crosslinking neighboring monomers
      thus indicating participation of the beta 7 strand in intersubunit interaction.
      Oxidation weakly affects the secondary and tertiary structure, does not affect
      the quaternary structure of alpha B-crystallin and HspB6, and shifts equilibrium
      between monomer and dimer of HspB8 towards dimer formation. It is concluded that
      the beta 7 strand participates in the intersubunit interaction of four human
      small heat shock proteins (alpha B-crystallin, HspB1, HspB6, HspB8) having
      different structure of beta2 strand of alpha-crystallin domain and different
      length and composition of variable N- and C-terminal tails.

PMID- 19856133
TI  - Differential expression of gonadotropin-releasing hormone (GnRH) in pancreas
      during rat pregnancy.
AB  - Many studies have shown that there is a relationship between gonadotropin
      releasing hormone (GnRH) and glucose metabolism, but little is known about the
      effects of GnRH on the pancreas. Our experiment investigated the effect of GnRH
      on pancreatic islet cell in Sprague-Dawley (SD) rats fed with high-cholesterol
      diet before and during pregnancy. We found that although high-cholesterol diet
      led to no significant difference of GnRH mRNA levels in pancreas in nonpregnant
      rats, it led to a marked increase of those in pregnant rats. Furthermore, in rats
      fed with standard laboratory chow, no significant differences were apparent in
      GnRH mRNA levels before and during gestation; however, when fed with high
      cholesterol diet, the GnRH mRNA levels increased significantly in pregnant rats.
      As results indicated both diets could lead to increase of PG mRNA in pancreas of
      pregnant rats. It is also demonstrated that the GnRH mRNA levels are positively
      associated with PG mRNA levels. Moreover, our data showed a significant increase
      in fasting insulin level in the Gestation group compared with Control. Such
      changes were contrary to the changes of GnRH level in the pancreas. This may
      imply that GnRH influences hormones secretion in the pancreas by autocrine and
      paracrine effects on islet cells.

PMID- 19856135
TI  - Coronary angiographic studies of impaired glucose regulation and coronary artery
      disease in Chinese nondiabetic subjects.
AB  - To investigate the prevalence and the extent of coronary artery disease (CAD) in
      nondiabetic Chinese patients with different categories of impaired glucose
      regulation (IGR): isolated impaired fasting glucose (I-IFG); isolated impaired
      glucose tolerance (I-IGT); and combined IFG and IGT (CGI). A total of 556
      nondiabetic subjects who had undergone coronary angiography were included in this
      study. Subjects were classified according to the 75-g oral glucose tolerance test
      result: normal glucose tolerance (NGT) (n = 278), I-IFG (n = 52), I-IGT (n =
      128), CGI (n = 98). Significant CAD is defined as the presence of one or more
      coronary vessels with the lumeninal reduction in diameter to >=50% in a given
      subject. The severity and extent of coronary atherosclerosis are defined by the
      Gensini score, the worst artery score, and the number of diseased vessels with
      significant coronary stenosis (number of diseased vessels). The prevalence of
      significant CAD in I-IFG and I-IGT groups were similar (67.3%, P = 0.207; 67.4%,
      P = 0.068, respectively) but both were higher comparing with NGT group (57.9%),
      however, it was considerably higher in CGI group (85.9%, P < 0.001). The Gensini
      score, worst artery score, and number of diseased vessels were similar in NGT, I
      IFG, and I-IGT groups, but all significantly increased in CGI group after
      adjustment for other traditional factors (all P < 0.001). Logistic regression
      analyses reveal fasting glucose but not 2-h glucose as a significant determinant
      in Gensini score, worst artery score, and number of diseased vessels. The
      prevalence and the extent of CAD did not differ significantly among subjects with
      NGT, I-IFG, and I-IGT, but increased significantly in those with CGI. Fasting
      glucose was more strongly associated with angiographically characterized coronary
      artery stenosis than 2-h glucose.

PMID- 19856134
TI  - Autonomic activity and glycemic homeostasis are maintained by precocious and low
      intensity training exercises in MSG-programmed obese mice.
AB  - Current research employed electrical records from superior vagus and sympathetic
      nerve branch that supply fat retroperitoneal tissue (RS nerve) to investigate
      whether very moderate swim training in obese-programmed mice would change
      sympathetic and parasympathetic autonomic nervous system activities. Neonatal
      mice were treated with monosodium L: -glutamate (MSG), during their first 5 days
      of life, to induce obesity. Mice started training on weaning, comprising free
      swimming 3 days/week, 15 min/day for 10 weeks. After 12 h fasting, the nerve
      electrical signals of the 90-day-old mice were processed to obtain firing rates.
      Blood samples were collected to measure glucose and insulin levels. Adrenal
      catecholamine content was measured. MSG treatment caused obesity. Hyperglycemia
      and hyperinsulinemia in MSG-obese mice, without any change in food intake, were
      obtained. Vagus firing rates were higher in obese mice than those in lean ones. A
      decrease in RS nerve activity and lower adrenal catecholamine stores have been
      observed. Swimming normalized blood glucose and insulin levels and MSG-obesity
      onset was attenuated by exercise. Vagus activity from obese mice decreased,
      whereas RS nerve activity and adrenal catecholamine levels increased in trained
      ones. Results suggest that autonomic activity imbalance and metabolic
      dysfunctions observed in MSG-obese mice were inhibited by precocious and moderate
      exercise training.

PMID- 19856136
TI  - Demographic, clinical, laboratory, ultrasonographic, and cytological features of
      patients with Hashimoto's thyroiditis: results of a university hospital of 769
      patients in Turkey.
AB  - We investigated the demographic and clinical features of patients with
      Hashimoto's thyroiditis who had been diagnosed and treated in Ege University, the
      main referral center in the Aegean region of Turkey. Medical records of patients
      who had been followed in the endocrinology clinic of Ege University were
      retrospectively evaluated. Patients who had been diagnosed as having any thyroid
      disorder were determined. Patients with Hashimoto's thyroiditis were selected
      among those patients. Seven hundred and sixty-nine patients fulfilled diagnostic
      criteria for Hashimoto's thyroiditis (725 females, 44 males; mean age 41.76 +/-
      12.49 years). 62.7% of patients were between 30 and 50 years of age. 53.3% of
      females and 63.6% of males had diffuse enlargement of the thyroid gland. TSH
      level was above 4.0 IU/l in 25.6% of females and 27.4% of males. Anti
      tyroglobulin antibody was positive in 92% of females and 93.2 % of males. Anti
      thyroid peroxidase antibody was positive in 98.4 % of females (713 patients) and
      100% of males. Thyroid ultrasonography demonstrated single nodule in 52.2% and
      multiple nodules in 11.3% of female patients; and single nodule 32% and multiple
      nodules in 20% of male patients. Fine-needle aspirations of the nodules were
      performed in 207 patients, and none of those biopsies was diagnosed as malignant.
      Women with suspicious biopsis were operated. After surgery, we found that, 2% (n
      = 4) of patients with FNAC diagnosis of suspicious biopsies were papillary
      carcinoma and the other patients (3% (n = 6)) were lymphocytic thyroiditis. Age
      and sex distribution and laboratory findings of our patients were comparable to
      the previous reports. Nodule formation was the most common ultrasonographic
      finding in our patients, probably due to pseudonodularity. We found four women
      patients with thyroid cancer in our population.

PMID- 19856137
TI  - The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G
      promoter polymorphism significantly influences plasma PAI-1 levels in women with
      polycystic ovary syndrome.
AB  - Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with
      increased PAI-1 levels, have been implicated in the pathogenesis of polycystic
      ovarian syndrome (PCOS). We investigated a possible influence of the promoter
      polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels
      in 126 PCOS patients and 97 healthy controls. Levels of total testosterone,
      luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma
      glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index
      (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment
      for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G
      gene polymorphisms were also performed. Total testosterone, fasting insulin, and
      PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients
      than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the
      combination genotype of 4G/4G and -844 A/A were 2.49 (95% confidence interval
      (CI), 1.4-4.44), 2.1 (95% CI, 1.43-3.08), and 2.9 (95% CI, 1.41-5.98),
      respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was
      significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G
      genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the
      combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the
      coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly
      high in PCOS women compared with controls. A trend to a positive interaction
      between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1
      levels and hypofibrinolysis, which is probably an important hereditary risk
      factor in PCOS.

PMID- 19856138
TI  - Administration of human leptin differentially affects parameters of cortisol
      secretion in socially housed female rhesus monkeys.
AB  - Chronic exposure to psychosocial stress may lead to a dysregulation of the limbic
      hypothalamic-pituitary-adrenal axis that results in a number of adverse health
      outcomes. The fat-derived hormone leptin has been indicated as a potential key
      component to maintaining homeostasis by enhancing glucocorticoid negative
      feedback. Using an established model of nonhuman primate social stress, notably
      social subordination, this study examined the effects of continuous leptin
      administration on cortisol secretion in female rhesus monkeys. The 20 subjects
      were maintained in stable five-member social groups with established dominance
      hierarchies. All females were ovariectomized but received estradiol throughout
      the study to maintain serum concentrations at early follicular phase levels.
      Three parameters of cortisol secretion were examined in dominant and subordinate
      females during control and leptin-treatment conditions: diurnal cortisol
      secretion; response to a dexamethasone suppression test; and response to a brief
      separation from their social group. We hypothesized that leptin supplementation
      would attenuate the hypercortisolemia characteristic of subordinate females.
      During baseline conditions, subordinate female rhesus monkeys had significantly
      lower levels of serum leptin compared with more dominant monkeys and were less
      sensitive to glucocorticoid negative feedback. Exogenous administration of leptin
      improved glucocorticoid negative feedback in subordinate females and decreased
      morning cortisol in all animals. However, there were no status differences in
      response to a social separation test and diurnal rhythm in cortisol during
      baseline conditions. However, leptin administration did not attenuate the
      increase in cortisol in response to a social separation. The data presented in
      this study demonstrate that leptin can attenuate several parameters of cortisol
      secretion in female rhesus monkeys and thus may play a role in the response of
      the adrenal glands to socio-environmental stimuli.

PMID- 19856139
TI  - Blood cell generation from the hemangioblast.
AB  - Understanding how blood cells are generated is important from a biological
      perspective but also has potential implications in the treatment of blood
      diseases. Such knowledge could potentially lead to defining new conditions to
      amplify hematopoietic stem cells (HSCs) or could translate into new methods to
      produce HSCs, or other types of blood cells, from human embryonic stem cells or
      induced pluripotent stem cells. Additionally, as most key transcription factors
      regulating early hematopoietic development have also been implicated in various
      types of leukemia, understanding their function during normal development could
      result in a better comprehension of their roles during abnormal hematopoiesis in
      leukemia. In this review, we discuss our current understanding of the molecular
      and cellular mechanisms of blood development from the earliest hematopoietic
      precursor, the hemangioblast, a precursor for both endothelial and hematopoietic
      cell lineages.

PMID- 19856140
TI  - Violence and depressive symptoms during pregnancy: a primary care study in
      Brazil.
AB  - AIM: To estimate the prevalence of violence, depressive symptoms, and associated
      factors during pregnancy in women attending antenatal care in Brazil. METHODS:
      Violence was assessed using a modified version of the abuse assessment screen
      (ASS), and depressive symptoms were evaluated using the primary care evaluation
      of mental disorders (PRIME-MD). Participants were pregnant women attending 18
      primary care units in Rio Grande do Sul, Brazil, between June 2006 and April
      2007. A total of 712 pregnant women participated, but only 627 of them responded
      the ASS. RESULTS: Experience of any lifetime violence was reported by 273 (43.4%)
      women and 114 (18.2%) reported violence during the current pregnancy. One-third
      of them (n = 211) reported lifetime domestic violence and 100 (15.9%) women
      reported this type of violence during the current pregnancy. Experience of
      domestic violence during pregnancy was more common in unemployed women, among
      those with two or more children, with a higher consumption of alcohol, and who
      had not planned their current pregnancy. Of the total of sample (n = 712), 198
      (27.8%) women reported six or more depressive symptoms. The presence of
      depressive symptoms during pregnancy was associated with low educational levels,
      living in a household with five or more people, and with higher consumption of
      alcohol during pregnancy. CONCLUSION: Pregnant women attending primary care are
      exposed to high rates of domestic violence, and many have clinically relevant
      depressive symptoms. Appropriate interventions to avoid or minimize the effects
      of violence and mental disorders to the well-being of the mothers and their
      babies are urgently required. Primary care services play an important role in
      identifying and supporting women at risk.

PMID- 19856141
TI  - Pediatric colloid cysts of the third ventricle: management considerations.
AB  - PURPOSE: Pediatric colloid cysts (CC) have a congenital origin, and yet, there
      are very few studies focussing exclusively on their occurrence in the pediatric
      population. Pediatric CC has been associated with more aggressive clinical and
      radiological patterns than their adult counterparts. In this study, undertaken on
      children with anterior third ventricular CC, excised using the interhemispheric
      transcallosal approach, the characteristic clinicoradiological features and
      management options are studied. METHODS: Five pediatric patients (aged 16 years
      or less; mean age 13.8 years; mean duration of symptoms:7.6 months) out of 38
      patients with CC operated between 1995 to 2009 were included. The clinical
      manifestations included those of raised intracranial pressure (n = 4);
      exacerbation of occipital headache on reading (n = 1); secondary optic atrophy (n
      = 3); and, drop attacks (n = 1). On computed tomography scan, the cyst was
      hyperdense, enhancing in two patients and not enhancing in three patients. All
      had bilateral lateral ventricular dilatation with periventricular lucency. On
      magnetic resonance imaging (n = 3), the cyst was T1 hypointense and T2 isointense
      in one, hyperintense on both T1 and T2 with a hypointense capsule and
      nonenhancing on contrast in one (with a giant colloid cyst), and T1 hyperintense
      and T2 hypointense in one patient. An interhemispheric, transcallosal trajectory
      combined with transforminal approach (n = 3); combined transforminal and
      subchoroidal approaches (n = 1); and, interforniceal approach (n = 1) were used.
      RESULTS: Total excision was performed in four patients. In one patient, a small
      part of capsule was left attached to thalamostriate vein. Symptoms of raised
      intracranial pressure showed improvement in all the patients with resolution of
      hydrocephalus. There was no tumor recurrence at follow-up. CONCLUSIONS: Pediatric
      colloid cysts are rarer than their adult counterparts due to their late detection
      only after manifestations of raised intracranial pressure, visual or cognitive
      dysfunction or drop attacks occur. Their radiological appearance varies depending
      upon the amount of mucoid content, cholesterol, proteins, and water content. The
      fast development of clinical manifestations in children may be related to rapid
      enlargement of cyst due to higher water content within them. The transcallosal
      approach is the "gold standard" of surgery and usually ensures gratifying and
      lasting results.

PMID- 19856142
TI  - Cryspovirus: a new genus of protozoan viruses in the family Partitiviridae.
AB  - The family Partitiviridae includes plant and fungal viruses with bisegmented
      dsRNA genomes and isometric virions in which the two genome segments are packaged
      separately and used as templates for semiconservative transcription by the viral
      polymerase. A new genus, Cryspovirus, has been approved for this family. Its name
      is based on that of the host genus, Cryptosporidium, which encompasses several
      species of apicomplexan parasites that infect a wide range of mammals, birds, and
      reptiles, and are a major cause of human diarrheal illness worldwide. The type
      species of the new genus is Cryptosporidium parvum virus 1. Distinguishing
      characteristics include infection of a protozoan host, a smaller capsid protein
      than found in other members of the family Partitiviridae, and sequence-based
      phylogenetic divergence.

PMID- 19856143
TI  - Inactivation of the proximal NPXY motif impairs early steps in LRP1 biosynthesis.
AB  - The proximal NPXY and distal NPXYXXL motifs in the intracellular domain of LRP1
      play an important role in regulation of the function of the receptor. The impact
      of single and double inactivating knock-in mutations of these motifs on receptor
      maturation, cell surface expression, and ligand internalization was analyzed in
      mutant and control wild-type mice and MEFs. Single inactivation of the proximal
      NPXY or in combination with inactivation of the distal NPXYXXL motif are both
      shown to be associated with an impaired maturation and premature proteasomal
      degradation of full-length LRP1. Therefore, only a small mature LRP1 pool is able
      to reach the cell surface resulting indirectly in severe impairment of ligand
      internalization. Single inactivation of the NPXYXXL motif revealed normal
      maturation, but direct impairment of ligand internalization. In conclusion, the
      proximal NPXY motif proves to be essential for early steps in the LRP1
      biosynthesis, whereas NPXYXXL appears rather relevant for internalization.

PMID- 19856144
TI  - Hepatocyte growth factor in cerebrospinal fluid is associated with mortality and
      recurrence of glioblastoma, and could be of prognostic value.
AB  - Malignant gliomas--glioblastoma multiforme and anaplastic astrocytoma--are among
      the most fatal forms of cancer in humans. It has been suggested that hepatocyte
      growth factor (HGF) is a reliable predictor of glioma malignancy; amounts of HGF
      are directly related to cellular proliferation, angiogenesis, low apoptotic rate,
      and poor prognosis (WHO III and IV). We measured the HGF content of cerebrospinal
      fluid (CSF) from patients with malignant glioma glioblastoma multiforme (WHO IV;
      n = 14), anaplastic astrocytoma (WHO III; n = 4), and meningioma (WHO I; n = 9),
      and from control subjects (n = 25), and found a high concentration of HGF in
      patients with malignant glioma. However, CSF concentrations from glioblastoma
      multiforme and anaplastic astrocytoma patients were not statistically
      significantly different (893 +/- 157 vs. 728 +/- 61, respectively; P > 0.01). A
      negative correlation between HGF and survival was found at five years of follow
      up (R = -0.922, R (2) = 0.850, P < 0.001). Also, the HGF concentration in CSF was
      a reliable means of explaining the highly variable survival of patients with
      malignant glioma. CSF concentrations of HGF higher than 500 pg/ml were associated
      with increased mortality whereas values higher than 850 pg/ml were associated
      with a brief tumor-free period after surgery (9 +/- 0.6 vs. 6 +/- 0.6 months,
      respectively, P < 0.001). Our findings support the idea that measurement of HGF
      in CSF could be a useful tool for monitoring the biological activity of malignant
      glioma. The findings will ultimately need to be confirmed in a much larger study.

PMID- 19856146
TI  - Characterization of a recombinant L-fucose isomerase from Caldicellulosiruptor
      saccharolyticus that isomerizes L-fucose, D-arabinose, D-altrose, and L
      galactose.
AB  - A recombinant L-fucose isomerase from Caldicellulosiruptor saccharolyticus was
      purified as a single 68 kDa band with an activity of 76 U mg(-1). The molecular
      mass of the native enzyme was 204 kDa as a trimer. The maximum activity for L
      fucose isomerization was at pH 7 and 75 degrees C in the presence of 1 mM Mn(2+).
      Its half-life at 70 degrees C was 6.1 h. For aldose substrates, the enzyme
      displayed activity in decreasing order for L-fucose, with a k (cat) of 11,910
      min(-1) and a K (m) of 140 mM, D-arabinose, D-altrose, and L-galactose. These
      aldoses were converted to the ketoses L-fuculose, D-ribulose, D-psicose, and L
      tagatose, respectively, with 24, 24, 85, 55% conversion yields after 3 h.

PMID- 19856145
TI  - Phospholipase D modulation by ceramide in senescence.
AB  - Phospholipase D (PLD) has been implicated in mitotic regulation and has been
      shown to be defective in cells following replicative senescence. We examined the
      source of changes in PLD activity in senescent human umbilical vein endothelial
      cells and in human diploid fibroblasts. Using fractionated cell components we
      found that the cytosolic components were necessary for maximum PLD activation. In
      comparison to low-passage cells, senescent cells showed a profound lack of PLD
      activatability. By recombining fractionated components from senescent and low
      passage cells, we found that in senescence the membrane component is defective in
      activating PLD implicating either the PLD enzyme itself or its interaction with
      PKC and/or ARF. The sphingolipid ceramide has been implicated in mediating
      senescence. Treatment with ceramide resulted in a decrease in PLD activity,
      implicating ceramide as the mediator of the inhibition.

PMID- 19856147
TI  - Inhibitory effect of curcumin on liver injury in a murine model of endotoxemic
      shock.
AB  - The effect of curcumin on lipopolysaccharide/D: -galactosamine (LPS/GalN)-induced
      acute shock model of liver injury was examined in mice. The simultaneous
      administration of LPS (5-20 microg kg(-1), i.p.) and GalN (700 mg kg(-1), i.p.)
      markedly increased the serum tumor necrosis factor-alpha (TNF-alpha), glutamic
      oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT), and massive
      hepatic necrosis and inflammation, leading to 100% lethality. Pre-administration
      of curcumin (100 mg kg(-1), i.p.) 3 h before induction with LPS/GalN imparted a
      large extent of protection against acute elevation in serum TNF-alpha and serum
      GOT/GPT. Hepatic necrosis and lethality caused by LPS/GalN was also greatly
      reduced by curcumin treatment. The results demonstrated that curcumin could
      protect mice from LPS/GalN-induced hepatic injury and inflammation through
      blockading TNF-alpha production, eventually raising the survival rate of septic
      shock-induced mice.

PMID- 19856148
TI  - [Analysis of the spectrum of nephropathies over 24 years in a West German center
      based on native kidney biopsies].
AB  - PURPOSE: The aim of the study was to analyze the occurrence of primary and
      secondary glomerulopathies as well as tubulointerstitial nephropathies over time
      and to assess potential changes in the disease spectrum. PATIENTS AND METHODS:
      The authors retrospectively analyzed all kidney biopsies performed in their
      institution between 1983 and 2006 as well as the clinical data at the time of
      biopsy. RESULTS: Between January 1983 and December 2006, 359 native kidney
      biopsies with sufficient material for histological analysis were performed (218
      men, 141 women; mean age 51.8 years). A mean of nine glomeruli per biopsy were
      obtained. Mean serum creatinine at the time of biopsy was 3.3 mg/dl. The most
      common indication for biopsy was nephrotic syndrome (31%), followed by renal
      insufficiency (29%) and proteinuria (14%). Primary glomerulopathies were found in
      51%, secondary glomerulopathies in 28%, tubulointerstitial renal diseases in 9%,
      and vascular renal diseases in 12%. Among the primary glomerulopathies, IgA
      nephropathy was the most common diagnosis (26%), followed by
      mesangioproliferative glomerulonephritis (17%), membranous glomerulonephritis
      (16%), minimal change disease (14%), focal segmental glomerulosclerosis (FSGS;
      13%), rapidly progressive glomerulonephritis (RPGN; 8%), and
      membranoproliferative glomerulonephritis (7%). Among the secondary
      glomerulopathies, the heterogeneous group of autoimmune diseases (26%) and
      diabetic nephropathy (25%) dominated. Comparing the period from 1983 to 1994 with
      1995 to 2006, a decrease in primary FSGS from 16% to 9% as well as in RPGN from
      14% to 1% was noticed, while among the secondary forms, autoimmune diseases with
      renal involvement increased from 14% to 31%. CONCLUSION: In the own patient
      population changes in the spectrum of primary and secondary glomerulopathies can
      be observed over time. Thereby, the distribution pattern of the various
      glomerulonephritides largely corresponds to the distribution described for other
      West European countries. An increase in the incidence of primary FSGS, as
      observed in non-European countries, could not be demonstrated.

PMID- 19856149
TI  - [The stable patient collective as a potential pitfall of prospective primary
      health-care studies. A qualitative inquiry among general practitioners].
AB  - BACKGROUND AND PURPOSE: Transparency and disclosure of problems in primary health
      care studies can add enormous information to the planning and conduction of such
      studies. By means of the inquiry of study participants, important data on study
      problems can be found out. Therefore, the aim of this qualitative study was to
      identify the causes of unexpected results of an intervention study in general
      practitioners' (GPs) practices by means of an inquiry of the participating GPs.
      The very study was about diagnosing alcohol- related health disorders at two
      points of time 1 year apart each with 2,400 primary health-care patients.
      METHODS: 39 of the 43 participating GPs of the study mentioned were asked by
      telephone about the possible causes of the unexpected study results. Data
      analysis was conducted according to the Qualitative Content Analysis of Philipp
      Mayring. RESULTS: The GPs mentioned problems that are already described in the
      international literature: the high expenses for study documentation, tabooed
      health topics, and declining participation motivation at the end of the study. A
      further cause of the unexpected study results was picked up: the repeated patient
      recruitment of this intervention study. It was unclear for the GPs whether they
      could include the same patients at the first and second recruitment point of
      time. Moreover, one main reason for the unexpected study results seems to be the
      stable patient collective of GPs' practices; according to that, only few new
      patients could be included at the second time point of recruitment. CONCLUSION:
      In primary health-care research requiring several time points for patient
      recruitment, one has to consider potential tabooed health topics and the special
      situation in primary health-care practices. This situation is characterized by a
      stable amount of known patients, even over years. The here-discussed causes of
      recruitment problems might be essential to avoid selection bias in primary health
      care studies.

PMID- 19856150
TI  - [Medical insurance aspects of peritoneal tumors with particular attention to
      peritoneal mesotheliomas].
AB  - Malignant peritoneal mesotheliomas arise mainly in male patients and the median
      age of initial diagnosis is about 56 years. Epitheloid subtype predominates in
      peritoneal mesotheliomas. Asbestos exposure is the best-known and most common
      risk factor associated with the development of both pleural and peritoneal
      mesotheliomas and, therefore, about 90% of cases can be assessed as asbestos
      associated. Patients with peritoneal mesotheliomas have distinctly higher
      asbestos burden of the lungs than patients with pleural mesotheliomas. The mean
      latency period between exposure and diagnosis of peritoneal mesothelioma ranges
      from 35 to 40 years and is comparable to that of pleural mesothelioma.
      Mesothelioma of the tunica vaginalis testis also belongs to the group of
      peritoneal mesotheliomas. No significant evidence exists for the classification
      of well-differentiated papillary mesothelioma, solitary fibrous tumor,
      adenomatoid tumor, primary peritoneal serous borderline tumor, and benign
      multicystic mesothelioma as asbestos-associated tumors. Except malignant
      mesotheliomas, the induction of other abdominal tumors is independent of an
      exposure to asbestos dust.

PMID- 19856151
TI  - [Pulmonary and pleural tuberculosis in the elderly].
AB  - With the increase of the proportion of the elderly in the total population more
      cases of pulmonary and extrapulmonary tuberculosis (TB) are observed in this age
      group as well. Symptoms of TB are unspecific, often less apparent in the elderly,
      and may therefore cause a delay in the diagnostic process. A history of TB and
      comorbidities are more common in elder as compared to younger TB patients. The
      tuberculin skin test is less frequently positive. The interferon-gamma-release
      assay is complementary and together with clinical, radiologic, and bacteriologic
      test results helpful for the diagnosis or the exclusion of an active or latent TB
      infection. Medical treatment of TB in the elderly follows the established
      guidelines in the same way as for younger patients. The likelihood of drug
      induced side effects and interactions with concomitant medications, however, is
      increased. Comorbidity and age-related immunosuppression may lead to a delay in
      the healing process. Higher age, comorbidity, and immunosuppression are
      predictors of an increased TB mortality. Even in a low-incidence country like
      Germany, TB should be recognized as an explanation for clinical symptoms
      particularly in the elderly patient group in order to allow an early diagnosis
      and therapy and thus a reduction of mortality and prevention of a further spread
      of this disease.

PMID- 19856152
TI  - [A patient with syncope].

PMID- 19856153
TI  - [Evaluation of the public-health intervention "Healthy Lower Rhine ... against
      Stroke" by phone surveys. A comparison of community knowledge of stroke by two
      surveys in the Lower Rhine Region, district of Wesel, Germany, 2002 and 2008].
AB  - BACKGROUND AND PURPOSE: From 2003 to 2008, the program "Healthy Lower Rhine ...
      against Stroke" was carried out by the Healthy Lower Rhine Network consisting of
      Health-Conference agencies of six neighboring districts and municipalities. The
      initiative aims primarily at improving public knowledge on stroke with regard to
      proper action - "A stroke is a medical emergency, so phone the emergency number
      112 immediately!" - and stroke warning signs and symptoms. The campaign is
      designed to eventually reduce prehospital time, i.e., delays from onset of
      symptoms to hospital delivery. In the Wesel district (North Rhine-Westphalia
      [NRW]) the local Health Conference commissioned two representative telephone
      surveys with a T(0) survey before the start of the program in 2003 and T(1) in
      2008 prior to the end of the 5 years' runtime. METHODS: The telephone survey was
      carried out by the CATI Laboratory (Computer-Assisted Telephone Interviews) of
      the Survey Center for Social Science (SUZ) in Duisburg in collaboration with the
      Institute of Health and Work NRW (LIGA.NRW) and the Health-Conference agency of
      the Wesel district. The study population was the adult community with about
      385,000 inhabitants. The random sample comprised 1,089 persons for the T(0)
      survey (02/18/02-03/28/02) and 1,104 persons were interviewed for the T(1) poll
      (03/18/08-04/05/08). RESULTS: While in 2002 a proportion of 31.9% of the
      interviewed persons knew not a single correct stroke symptom, in 2008 this
      portion amounted to 27.3%. Three or more correct signs were mentioned by 18.6% in
      the T0 survey versus 25.5% in 2008 (T(1) survey). Symptoms which were mentioned
      significantly more frequently in 2008 than in 2002 were hemiplegia and dropping
      corner of the mouth (+5.3%), respectively, numbness/paresthesia (+17.9%), trouble
      speaking or understanding (+6.1%), and trouble seeing/visual impairment (+4.3%).
      When being asked: "What would you do in case of stroke?", 69% of the answers in
      2008 were correct (call emergency number 112). There were no significant
      differences in knowledge of risk factors. About 25% of participants in 2008
      stated, that they remembered the stroke awareness campaign or related events.
      CONCLUSION: The present study shows a moderate improvement of community knowledge
      about stroke with respect to symptoms and proper action in the course of the 5
      years' public-health intervention. In comparison to similar surveys performed in
      2000 and 2004, especially knowledge of correct action in case of emergency
      (stroke = medical emergency = call 112) improved. Still, there are persisting
      gaps in knowledge about stroke in the community, which make further efforts of
      improving this knowledge recommendable.

PMID- 19856154
TI  - [Vertebral granulocytic sarcoma--a rare differential diagnosis of vertebral
      deformity].
AB  - CASE REPORT: The authors report on an 83-year-old woman who presented with back
      pain with sudden onset 6 weeks prior to admission. A radiograph of the lumbar
      spine revealed a vertebral deformity. An MRI (magnetic resonance imaging) scan
      showed bone marrow edema of the affected vertebra. Blood counts on laboratory
      tests were normal at the time of admission. Due to continuing pain vertebroplasty
      was performed, and bone biopsies were taken during the procedure. The biopsies
      showed infiltration of the marrow space with granulocytic sarcoma (chloroma), a
      tumor, which may precede the onset of acute myelogenous leukemia. CONCLUSION:
      This case underlines the need for a thorough diagnostic work-up in patients with
      ongoing complaints of an assumed osteoporotic vertebral fracture. Granulocytic
      sarcoma represents a rare differential diagnosis of vertebral deformity.

PMID- 19856155
TI  - [Acute renal failure and hypercalcemia in an AIDS patient on tenofovir and low
      dose vitamin D therapy with immune reconstitution inflammatory syndrome].
AB  - BACKGROUND: Tenofovir-containing antiviral therapy might result in acute renal
      failure and is able to induce tubular dysfunction with hypocalcemia. On the other
      hand, hypercalcemia induced by intoxication with colecalciferol has been
      described to induce renal failure in HIV-positive individuals as well. Here, the
      authors describe the unusual case of reversible renal failure due to
      hypercalcemia in a patient with low-dose colecalciferol substitution treated with
      tenofovir. CASE REPORT: A 31-year-old HIV-positive female, CDC stage C3, was
      admitted to the authors' hospital with progressive renal failure and
      hypercalcemia. Antiretroviral therapy consisted of tenofovir and emtricitabine in
      combination with efavirenz. Additionally, she was on low-dose vitamin D(3)
      substitution (25 microg/d) and calcium supplementation (500 mg/d) due to systemic
      steroid treatment. CONCLUSION: Additionally to regular control of renal function,
      serologic level of calcium should be supervised in patients concomitantly treated
      with tenofovir and colecalciferol.

PMID- 19856159
TI  - Spermatogenesis and cycle of the seminiferous epithelium.
AB  - Spermatogenesis is a complex biological process of cellular transformation that
      produces male haploid germ cells from diploid spermatogonial stem cells. This
      process has been simplified morphologically by recognizing cellular associations
      or 'stages' and 'phases' of spermatogenesis, which progress through precisely
      timed and highly organized cycles. These cycles of spermatogenesis are essential
      for continuous sperm production, which is dependent upon numerous factors, both
      intrinsic (Sertoli and germ cells) and extrinsic (androgens, retinoic acids), as
      well as being species-specific.

PMID- 19856156
TI  - [Cerebral T wave inversion and prolonged QTc interval in the surface ECG of a
      patient with bacterial meningitis].

PMID- 19856160
TI  - Testicular development and spermatogenesis: harvesting the postgenomics bounty.

PMID- 19856161
TI  - Estrogens and spermatogenesis.

PMID- 19856162
TI  - Selenium, a key element in spermatogenesis and male fertility.
AB  - Selenium is essential for normal spermatogenesis of mammals and its critical role
      is mainly mediated by two selenoproteins, namely phospholipid hydroperoxide
      glutathione peroxidase (PHGPx/GPx4) and Selenoprotein P. PHGPx/GPx4 is the major
      selenoprotein expressed by germ cells in the testis, having multiple functions
      and representing the pivotal link between selenium, sperm quality and male
      fertility. Selenoprotein P is a plasma protein that is required for selenium
      supply to the testis. In the last years, nutritional studies and experimental
      animal models lacking/overexpressing a specific PHGPx isoform and selenoprotein P
      have highly expanded our understanding on how the male reproductive system
      depends on selenium. The focus of this review, is to report and discuss the most
      relevant and recent findings in this field. Clinical data have pointed to a
      correlation between abnormal PHGPx content in sperm and disturbance of human male
      fertility. However, additional evidence is still required to draw any definitive
      conclusions about therapeutical strategies for improving fertility by selenium
      administration.

PMID- 19856164
TI  - Inflammatory networks in the control of spermatogenesis : chronic inflammation in
      an immunologically privileged tissue?
AB  - Spermatogenesis is a complex, organized process involving intimate interactions
      between the developing germ cells and supporting Sertoli cells. The process is
      also highly regulated. Studies suggest that regulation in the seminiferous
      epithelium involves molecules normally associated with either immune or
      inflammatory processes; in particular, interleukin 1a (IL1a), IL6, tumor necrosis
      factor (TNFa), activin A and nitric oxide (NO). While there is considerable
      evidence that these inflammatory mediators have effects on spermatogonial and
      spermatocyte development as well as critical supportive functions of the Sertoli
      cells, which are undoubtedly of considerable importance during testicular
      inflammation, there remains some skepticism regarding the significance of these
      molecules with respect to normal testicular function. Nonetheless, it is evident
      that expression of these regulators varies across the cycle of the seminiferous
      epithelium in a consistent manner, with major changes in production coinciding
      with key events within the cycle. This review summarizes the evidence supporting
      the hypothesis that inflammatory cytokines play a role in normal testicular
      spermatogenesis, as well as in the etiology of inflammation induced sub
      fertility. The balance of data leads to the striking conclusion that the cycle of
      the seminiferous epithelium resembles a chronic inflammatory event. This appears
      to be a somewhat paradoxical assertion, since the testis is an immunologically
      privileged tissue based on its well-established ability to support grafts with
      minimal rejection responses. However, it may be argued that local
      immunoregulatory mechanisms, which confer protection from immunity on both
      transplanted tissues and the developing spermatogenic cells, are equally
      necessary to prevent local inflammation responses associated with the
      spermatogenic process from activating the adaptive immune response.

PMID- 19856163
TI  - Extracellular matrix and its role in spermatogenesis.
AB  - In adult mammalian testes, such as rats, Sertoli and germ cells at different
      stages of their development in the seminiferous epithelium are in close contact
      with the basement membrane, a modified form of extracellular matrix (ECM). In
      essence, Sertoli and germ cells in particular spermatogonia are "resting" on the
      basement membrane at different stages of the seminiferous epithelial cycle,
      relying on its structural and hormonal supports. Thus, it is not entirely
      unexpected that ECM plays a significant role in regulating spermatogenesis,
      particularly spermatogonia and Sertoli cells, and the blood-testis barrier (BTB)
      constituted by Sertoli cells since these cells are in physical contact with the
      basement membrane. Additionally, the basement membrane is also in close contact
      with the underlying collagen network and the myoid cell layers, which together
      with the lymphatic network, constitute the tunica propria. The seminiferous
      epithelium and the tunica propria, in turn, constitute the seminiferous tubule,
      which is the functional unit that produces spermatozoa via its interaction with
      Leydig cells in the interstitium. In short, the basement membrane and the
      underlying collagen network that create the acellular zone of the tunica propria
      may even facilitate cross-talk between the seminiferous epithelium, the myoid
      cells and cells in the interstitium. Recent studies in the field have illustrated
      the crucial role of ECM in supporting Sertoli and germ cell function in the
      seminiferous epithelium, including the BTB dynamics. In this chapter, we
      summarize some of the latest findings in the field regarding the functional role
      of ECM in spermatogenesis using the adult rat testis as a model. We also high
      light specific areas of research that deserve attention for investigators in the
      field.

PMID- 19856165
TI  - Transcription regulation in spermatogenesis.

PMID- 19856166
TI  - Proteases and their cognate inhibitors of the serine and metalloprotease
      subclasses, in testicular physiology.

PMID- 19856167
TI  - Antioxidant systems and oxidative stress in the testes.

PMID- 19856168
TI  - Nitric oxide and cyclic nucleotides: their roles in junction dynamics and
      spermatogenesis.
AB  - Spermatogenesis is a highly complicated process in which functional spermatozoa
      (haploid, 1n) are generated from primitive mitotic spermatogonia (diploid, 2n).
      This process involves the differentiation and transformation of several types of
      germ cells as spermatocytes and spermatids undergo meiosis and differentiation.
      Due to its sophistication and complexity, testis possesses intrinsic mechanisms
      to modulate and regulate different stages of germ cell development under the
      intimate and indirect cooperation with Sertoli and Leydig cells, respectively.
      Furthermore, developing germ cells must translocate from the basal to the apical
      (adluminal) compartment of the seminiferous epithelium. Thus, extensive junction
      restructuring must occur to assist germ cell movement. Within the seminiferous
      tubules, three principal types of junctions are found namely anchoring junctions,
      tight junctions, and gap junctions. Other less studied junctions are desmosome
      like junctions and hemidesmosome junctions. With these varieties of junction
      types, testes are using different regulators to monitor junction turnover. Among
      the uncountable junction modulators, nitric oxide (NO) is a prominent candidate
      due to its versatility and extensive downstream network. NO is synthesized by
      nitric oxide synthase (NOS). Three traditional NOS, specified as endothelial NOS
      (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS), and one testis-specific
      nNOS (TnNOS) are found in the testis. For these, eNOS and iNOS were recently
      shown to have putative junction regulation properties. More important, these two
      NOSs likely rely on the downstream soluble guanylyl cyclase/cGMP/protein kinase G
      signaling pathway to regulate the structural components at the tight junctions
      and adherens junctions in the testes. Apart from the involvement in junction
      regulation, NOS/NO also participates in controlling the levels of cytokines and
      hormones in the testes. On the other hand, NO is playing a unique role in
      modulating germ cell viability and development, and indirectly acting on some
      aspects of male infertility and testicular pathological conditions. Thus, NOS/NO
      bears an irreplaceable role in maintaining the homeostasis of the
      microenvironment in the seminiferous epithelium via its different downstream
      signaling pathways.

PMID- 19856169
TI  - The Sertoli cell cytoskeleton.
AB  - The cytoskeleton of terminally differentiated mammalian Sertoli cells is one of
      the most elaborate of those that have been described for cells in tissues. Actin
      filaments, intermediate filaments and microtubules have distinct patterns of
      distribution that change during the cyclic process of spermatogenesis. Each of
      the three major cytoskeletal elements is either concentrated at or related in
      part to intercellular junctions. Actin filaments are concentrated in unique
      structures termed ectoplasmic specializations that function in intercellular
      adhesion, and at tubulobulbar complexes that are thought to be involved with
      junction internalization during sperm release and movement of spermatocytes
      through basal junctions between neighboring Sertoi cells. Intermediate filaments
      occur in a perinuclear network which has peripheral extensions to desmosome-like
      junctions with adjacent cells and to small hemidesmosome-like attachments to the
      basal lamina. Unlike in most other epithelia where the intermediate filaments are
      of the keratin type, intermediate filaments in mature Sertoli cells are of the
      vimentin type. The function of intermediate filaments in Sertoli cells in not
      entirely clear; however, the pattern of filament distribution and the limited
      experimental data available are consistent with a role in maintaining tissue
      integrity when the epithelium is mechanically stressed. Microtubules are abundant
      in Sertoli cells and are predominantly oriented parallel to the long axis of the
      cell. Microtubules are involved with maintaining the columnar shape of Sertoli
      cells, with transporting and positioning organelles in the cytoplasm, and with
      secreting seminiferous tubule fluid. In addition, microtubule-based transport
      machinery is coupled to intercellular junctions to translocate and position
      adjacent spermatids in the epithelium. Although the cytoskeleton of Sertoli cells
      has structural and functional properties common to cells generally, there are a
      number of properties that are unique and that appear related to processes
      fundamental to spermatogenesis and to interfacing somatic cells both with similar
      neighboring somatic cells and with differentiating cells of the germ cell line.

PMID- 19856170
TI  - Blood-testis barrier, junctional and transport proteins and spermatogenesis.

PMID- 19856172
TI  - The role of the Leydig cell in spermatogenic function.

PMID- 19856171
TI  - Cross-talk between tight and anchoring junctions-lesson from the testis.
AB  - Spermatogenesis takes place in the seminiferous tubules in adult testes such as
      rats, in which developing germ cells must traverse the seminiferous epithelium
      while spermatogonia (2n, diploid) undergo mitotic and meiotic divisions, and
      differentiate into elongated spermatids (1n, haploid). It is conceivable that
      this event involves extensive junction restructuring particularly at the blood
      testis barrier (BTB, a structure that segregates the seminiferous epithelium into
      the basal and the adluminal compartments) that occurs at stages VII-VIII of the
      seminiferous epithelial cycle. As such, cross-talk between tight (TJ) and
      anchoring junctions [e.g., basal ectoplasmic specialization (basal ES), adherens
      junction (AJ), desmosome-like junction (DJ)] at the BTB must occur to coordinate
      the transient opening of the BTB to facilitate preleptotene spermatocyte
      migration. Interestingly, while there are extensively restructuring at the BTB
      during the epithelial cycle, the immunological barrier function of the BTB must
      be maintained without disruption even transiently. Recent studies using the
      androgen suppression and Adjudin models have shown that anchoring junction
      restructuring that leads to germ cell loss from the seminiferous epithelium also
      promotes the production of AJ (e.g., basal ES) proteins (such as N-cadherins,
      catenins) at the BTB site. We postulate the testis is using a similar mechanism
      during spermatogenesis at stage VIII of the epithelial cycle that these induced
      basal ES proteins, likely form a "patch" surrounding the BTB, transiently
      maintain the BTB integrity while TJ is "opened", such as induced by TGF-b3 or
      TNFa, to facilitate preleptotene spermatocyte migration. However, in other stages
      of the epithelial cycle other than VII and VIII when the BTB remains "closed"
      (for approximately 10 days), anchoring junctions (e.g., AJ, DJ, and apical ES)
      restructuring continues to facilitate germ cell movement. Interestingly, the
      mechanism(s) that governs this communication between TJ and anchoring junction
      (e.g., basal ES and AJ) in the testis has remained obscure until recently.
      Herein, we provide a critical review based on the recently available data
      regarding the cross-talk between TJ and anchoring junction to allow simultaneous
      maintenance of the BTB and germ cell movement across the seminiferous epithelium.

PMID- 19856173
TI  - Major and minor QTL and epistasis contribute to fatty acid compositions and oil
      concentration in high-oil maize.
AB  - High-oil maize is a useful genetic resource for genomic investigation in plants.
      To determine the genetic basis of oil concentration and composition in maize
      grain, a recombinant inbred population derived from a cross between normal line
      B73 and high-oil line By804 was phenotyped using gas chromatography, and
      genotyped with 228 molecular markers. A total of 42 individual QTL, associated
      with fatty acid compositions and oil concentration, were detected in 21 genomic
      regions. Five major QTL were identified for measured traits, one each of which
      explained 42.0% of phenotypic variance for palmitic acid, 15.0% for stearic acid,
      27.7% for oleic acid, 48.3% for linoleic acid, and 15.7% for oil concentration in
      the RIL population. Thirty-six loci were involved in 24 molecular marker pairs of
      epistatic interactions across all traits, which explained phenotypic variances
      ranging from 0.4 to 6.1%. Seven of 18 mapping candidate genes related to lipid
      metabolism were localized within or were close to identified individual QTL,
      explaining 0.7-13.2% of the population variance. These results demonstrated that
      a few major QTL with large additive effects could play an important role in
      attending fatty acid compositions and increasing oil concentration in used
      germplasm. A larger number of minor QTL and a certain number of epistatic QTL,
      both with additive effects, also contributed to fatty acid compositions and oil
      concentration.

PMID- 19856174
TI  - Iso-lines and inbred-lines confirmed loci that underlie resistance from cultivar
      'Hartwig' to three soybean cyst nematode populations.
AB  - Soybean [Glycine max (L.) Merr.] cultivars varied in their resistance to
      different populations of the soybean cyst nematode (SCN), Heterodera glycines,
      called HG Types. The rhg1 locus on linkage group G was necessary for resistance
      to all HG types. However, the loci for resistance to H. glycines HG Type 1.3-
      (race 14) and HG Type 1.2.5- (race 2) of the soybean cyst nematode have varied in
      their reported locations. The aims were to compare the inheritance of resistance
      to three nematode HG Types in a population segregating for resistance to SCN and
      to identify the underlying quantitative trait loci (QTL). 'Hartwig', a soybean
      cultivar resistant to most SCN HG Types, was crossed with the susceptible
      cultivar 'Flyer'. A total of 92 F5-derived recombinant inbred lines (RILs; or
      inbred lines) and 144 molecular markers were used for map development. The rhg1
      associated QTL found in earlier studies were confirmed and shown to underlie
      resistance to all three HG Types in RILs (Satt309; HG Type 0, P = 0.0001 R (2) =
      22%; Satt275; HG Type 1.3, P = 0.001, R (2) = 14%) and near isogeneic lines
      (NILs; or iso-lines; Satt309; HG Type 1.2.5-, P = 0.001 R (2) = 24%). A new QTL
      underlying resistance to HG Type 1.2.5- was detected on LG D2 (Satt574; P =
      0.001, R (2) = 11%) among 14 RILs resistant to the other HG types. The locus was
      confirmed in a small NIL population consisting of 60 plants of ten genotypes (P =
      0.04). This QTL (cqSCN-005) is located in an interval previously associated with
      resistance to both SDS leaf scorch from 'Pyramid' and 'Ripley' (cqSDS-001) and
      SCN HG Type 1.3- from Hartwig and Pyramid. The QTL detected will allow marker
      assisted selection for multigenic resistance to complex nematode populations in
      combination with sudden death syndrome resistance (SDS) and other agronomic
      traits.

PMID- 19856175
TI  - Use of two validated in vitro tests to assess the embryotoxic potential of
      mycophenolic acid.
AB  - Mycophenolate mofetil is a widely used immunosuppressive drug that recently has
      been categorized as a human teratogen. Animal experiments indicate a teratogenic
      potential of the drug, but so far, it has not been studied in embryotoxicity in
      vitro assays. The aim of this study was to evaluate the in vitro embryotoxic
      potential of mycophenolic acid and investigate the ability of such tests to
      detect its embryotoxic potential. We used two validated assays: the rat whole
      embryo culture and the murine embryonic stem cell test. Rat embryos cultured from
      gestational day 9.5 for 48 h with the drug showed dysmorphogenic development
      already at a concentration of 250 microg mycophenolic acid/l medium. At
      concentrations of 750 microg/l and more, all rat embryos exhibited malformations.
      The main effects were defective yolk sac blood circulation, neural tube defects
      (open cranial neural pore), malformations of the head with missing eye anlagen
      and heart anomalies. Moreover, the exposed embryos showed a concentration
      dependent decrease in protein content, crown-rump length, number of somites and
      morphological score. The murine embryonic stem cell test was slightly more
      sensitive. Proliferation and differentiation of the ES-D3-cells were
      significantly impaired at concentrations of 31 and 125 microg mycophenolic acid/l
      medium, respectively. In the differentiation assay, at a concentration of 125
      microg mycophenolic acid/l medium and more, the number of wells with
      differentiated cardiomyocytes significantly decreased. Additionally, a
      cytotoxicity assay with balb/c 3T3 mouse fibroblasts was used to compare the
      proliferation and vitality of embryonic cells with adult cells. In the balb/c 3T3
      cytotoxicity assay, the number of vital mouse fibroblasts significantly decreased
      at a mycophenolic acid concentration of 62 microg/l and more. In conclusion, by
      using the two validated in vitro tests, we showed that mycophenolic acid exhibits
      a pronounced embryotoxic potential at cytotoxic concentrations. This result from
      validated in vitro tests is of special interest, because it supports the use of
      the tests to detect human teratogens.

PMID- 19856176
TI  - The use of 35S and Tnos expression elements in the measurement of genetically
      engineered plant materials.
AB  - An online survey was conducted by the International Life Sciences Institute, Food
      Biotechnology Committee, on the use of qualitative and quantitative polymerase
      chain reaction (PCR) assays for cauliflower mosaic virus 35S promoter and
      Agrobacterium tumefaciens Tnos DNA sequence elements for the detection of
      genetically engineered (GE) crop plant material. Forty-four testing laboratories
      around the world completed the survey. The results showed the widespread use of
      such methods, the multiplicity of published and in-house methods, and the variety
      of reference materials and calibrants in use. There was an interest on the part
      of respondents in validated quantitative assays relevant to all GE events that
      contain these two genetic elements. Data are presented by testing two variations
      each of five published real-time quantitative PCR methods for 35S detection on
      eight maize reference materials. The results showed that two of the five methods
      were not suitable for all the eight reference materials, with poor linear
      regression parameters and multiple PCR amplification products for some of the
      reference materials. This study demonstrates that not all 35S methods produce
      satisfactory results, emphasizing the need for method validation.

PMID- 19856177
TI  - Incarnation and animation: physical versus representational deficits of body
      integrity.
AB  - Two apparently disparate phenomena of defective body integrity are reviewed. The
      first concerns dysmelia, characterized by the congenital absence or deformation
      of limbs, and the focus of the review is on phantom sensations of people with
      this kind of physical integrity disorder. The second phenomenon consists of non
      psychotic individuals' desire to have a healthy limb amputated, which is
      interpreted as a mismatch between the physical integrity of a particular limb and
      its representation in multimodal cortical areas of the brain. We outlined
      commonalities and differences between the two conditions and note the absence, in
      both areas of research, of a unified theory that would account for the reported
      phenomenology. Phantom limbs in dysmelia and the desire for limb amputation most
      likely are the consequence of very early developmental dissociations between
      physical and phenomenal body shapes. They are mirror images of one another in
      that the former constitutes an "animation without incarnation" and, the latter,
      an "incarnation without animation".

PMID- 19856178
TI  - No effect of autologous growth factors (AGF) around ungrafted loaded implants in
      dogs.
AB  - Autologous growth factors (AGF) is a growth-factor-rich concentrate of platelets,
      white blood cells and fibrinogen. Application of AGF was presumed to improve
      implant fixation and gap healing of non-grafted, loaded implants. We inserted one
      loaded titanium implant intra-articularly in each medial femoral condyle of eight
      dogs. Each implant was surrounded by a 0.75 mm gap. One implant in each dog was
      coated with AGF prior to implantation whereas the contralateral implant served as
      a control. AGF was prepared by isolating the buffy-coat from blood and further
      concentrated using an Interpore Cross UltraConcentrator. Platelet counts were
      increased from a median baseline of 168x10(3)/microl to 1003x10(3)/microl in AGF.
      However, AGF had no significant effect on implant fixation or bone formation.
      Even though AGF increased ultimate shear strength and energy absorption by
      approximately 50%, these differences had a p-value less than 0.05. The sample
      size in this study was small and any negative conclusions should be taken with
      caution due to low statistical power. We have previously demonstrated that AGF
      significantly improves fixation and incorporation of grafted implants. AGF might
      require mixing with an osteoconductive grafting material in order to provide a
      scaffold on which to foster bone growth and to keep the growth factors on
      location for a prolonged period.

PMID- 19856180
TI  - Familial Takayasu's arteritis in female siblings.
AB  - Takayasu's arteritis (TA) is a rare chronic vasculitis of the aorta and its main
      branches. Infectious agents or autoimmunity are thought to influence the
      pathophysiology. Ethnic preponderance in East Asia and usually affects young
      Asian women suggesting a possible role of genetic factor in the etiology. We
      present a rare case of familial TA in female siblings with the involvement of the
      main branches of aortic arch and renal arteries described by three-dimensional
      computed tomography (3D-CT). This case is rare familial TA in female siblings
      with CT angiography, which is feasible in diagnosis and informative for the stage
      of TA.

PMID- 19856179
TI  - De Quervain's syndrome associated with osteopoikilosis: a case report and review
      of the literature.
AB  - Osteopoikilosis is a rare, usually asymptomatic, autosomal-dominant bone
      disorder, which is generally diagnosed incidentally on X-ray. De Quervain's
      syndrome is a disorder characterized by pain on the radial (thumb) side of the
      wrist, impairment of thumb function and thickening of the ligamentous structure
      covering the tendons in the first dorsal compartment of the wrist. In this case
      report, we present a young woman with De Quervain's syndrome associated with
      osteopoikilosis.

PMID- 19856181
TI  - Transglutaminases, involucrin, and loricrin as markers of epidermal
      differentiation in skin substitutes derived from human sweat gland cells.
AB  - BACKGROUND/PURPOSE: In a multi-project research line, we are currently testing
      whether a morphologically and functionally near normal epidermis can be cultured
      from human sweat gland (SG) cells and be used as a skin substitute. The present
      study focuses on the stratum corneum of the epidermis that assumes a vital
      barrier function for the skin. The main process in the formation of the cornified
      cell envelope in human epidermis, i.e. crosslinking of proteins and lipids, is
      catalyzed by several transglutaminases (TG). Therefore, we compared the
      expression patterns of various TG and their substrates in SG-derived versus
      keratinocyte-derived epidermal substitutes. METHODS: Sweat gland cells,
      keratinocytes, and fibroblasts were isolated from human skin samples and
      cultivated separately to generate epidermal substitutes. These were transplanted
      onto the back of athymic rats. After 2 weeks, the transplants were excised and
      analyzed histologically as well as by indirect immunofluorescence. We looked at
      the expression of TG1, 3, 5, and their substrates involucrin and loricrin
      (=markers of epidermal differentiation) in SG-derived and keratinocyte-derived
      skin substitutes as well as in normal skin. RESULTS: The SG cell-derived
      epidermis was near normal anatomically, formed a cornified cell envelope and
      demonstrated TG1, 3, and 5 as well as involucrin and loricrin expression patterns
      similar to those found in keratinocyte-derived epidermis and normal control skin.
      CONCLUSION: These findings support the thesis that SG cells have the potential to
      form a near normal stratified epidermal analog that might be used as a skin
      substitute. The expression of TG1 and 3, not normally expressed in human SG,
      suggests the presence of re-programmed SG cells and/or stem cells capable of both
      de novo generating and maintaining an epidermis.

PMID- 19856182
TI  - Hepatoid carcinoma of the ovary with sex cord stromal tumor: a previously
      unrecognized association.
AB  - BACKGROUND: Hepatoid carcinoma (HC) of ovary is a rare type of epithelial tumor
      composed mainly of epithelioid cells with abundant acidophilic cytoplasm,
      histologically indistinguishable from hepatocellular carcinoma. We report a
      previously unrecognized case of HC of ovary concurrent with a Sertoli cell tumor.
      CASE REPORT: A 42-year-old woman patient with a long-term history of hepatitis C
      presented with a mass of left ovary without evidence of hepatic tumor. After
      initial diagnosis of primary ovarian carcinoma (FIGO Stage I), she had
      experienced a first recurrence in upper abdomen. Histologically, the primary
      tumor was composed of epithelioid cells with "hepatoid features" in association
      with a sex cord stromal tumor of Sertoli-type. Immunohistochemistry hepatoid
      cells stained positively for hepatocyte paraffin-1, alpha-fetoprotein and alpha-1
      antitrypsin; moreover, Sertoli-type cells were positive for alpha-inhibin,
      calretinin and CD99. A final diagnosis of HC concurrent with Sertoli-type tumor
      was made. CONCLUSION: The occurrence of this unreported association of HC with
      Sertoli-like tumor, the problems of differential diagnosis and therapeutic
      management of these tumors are the subject of this presentation. A diagnosis of
      ovarian metastasis from hepatocellular carcinoma is easy in patients with known
      primary tumor of liver and should be always excluded in these cases as an
      hepatoid variant of yolk sac tumor. Immunohistochemistry is not useful in these
      cases. However, a combination of clinical and pathological features is necessary
      for a correct diagnosis.

PMID- 19856183
TI  - Early post-partum diabetes mellitus screening rates in patients with history of
      gestational diabetes.
AB  - INTRODUCTION: Patients with history of gestational diabetes (GDM) are at high
      risk for developing diabetes mellitus (DM) after pregnancy. This study
      investigates the rate of GDM patients who received screening and the prevalence
      of DM in the early post-partum period. MATERIALS AND METHODS: This study included
      78 patients diagnosed and treated for GDM between January 2005 and December 2007.
      They were evaluated whether or not they were screened with 75 g oral glucose
      tolerance test (OGTT) or fasting blood glucose measurement at post-partum 6-12
      week period. The rates of DM and impaired glucose tolerance (IGT) were
      determined. RESULTS: Of 78 GDM patients only 10 (12.8%) patients were screened
      with OGTT and 27 (34.6%) patients were screened with fasting blood glucose (FBG)
      measurement. 41 (52.6%) patients did not receive any post-partum screening.
      Insulin treated patients during pregnancy underwent OGTT more frequently (p =
      0.008). We found that 61% of the patients who did not receive any screening test
      were seen by a doctor for any reason during this period. DM was diagnosed in 50%
      of patients who underwent OGTT and 7.4% of patients who underwent FBG measurement
      during early post-partum period (p = 0.013). CONCLUSION: Despite the fact that
      GDM is generally strictly and carefully monitored during pregnancy, it is usually
      neglected in the post-partum period. Insulin treated patients during pregnancy
      should be informed better for post-partum screening with OGTT. OGTT appears to be
      a better way of screening to diagnose DM.

PMID- 19856185
TI  - Experts see it all: configural effects in action observation.
AB  - Biological motion perception is influenced by observers' familiarity with the
      observed action. Here, we used classical dance as a means to investigate how
      visual and motor experience modulates perceptual mechanism for configural
      processing of actions. Although some ballet moves are performed by only one
      gender, male and female dancers train together and acquire visual knowledge of
      all ballet moves. Twenty-four expert ballet dancers (12 female) and matched non
      expert participants viewed pairs of upright and inverted point light female and
      common dance movements. Visual discrimination between different exemplars of the
      same movement presented upright was significantly better in experts than
      controls, whilst no differences were found when the same stimuli were presented
      upside down. These results suggest expertise influences configural action
      processing. Within the expert group, effects were stronger for female
      participants than for males, whilst no differences were found between movement
      types. This observer gender effect could suggest an additional role for motor
      familiarity in action perception, over and above the visual experience. Our
      results are consistent with a specific motor contribution to configural
      processing of action.

PMID- 19856186
TI  - New insights into perinatal testicular torsion.
AB  - Perinatal testicular torsion is a relatively rare event that remains unrecognized
      in many patients or is suspected and treated accordingly only after an avoidable
      loss of time. The authors report their own experience with several patients, some
      of them quite atypical but instructive. Missed bilateral torsion is an issue, as
      are partial torsion, possible antenatal signs, and late presentation. These data
      are discussed together with the existing literature and may help shed new light
      on the natural course of testicular torsion and its treatment. The most important
      conclusion is that a much higher index of suspicion based on clinical findings is
      needed for timely detection of perinatal torsion. It is the authors' opinion that
      immediate surgery is mandatory not only in suspected bilateral torsions but also
      in cases of possible unilateral torsions. There is no place for a more fatalistic
      "wait-and-see" approach. Whenever possible, even necrotic testes should not be
      removed during surgery because some endocrine function may be retained.

PMID- 19856187
TI  - Anal canal duplication.
AB  - INTRODUCTION: Anal canal duplication (ACD) is an extremely rare congenital
      intestinal anomaly. ACD is defined as a second anal orifice located posterior to
      the true anus ending blindly without connection to the rectum. Usually, there are
      no other accompanying hindgut pathologies. Patients are often asymptomatic and
      apply to clinics with their parent's attention. CASE 1: A 9-month-old girl was
      referred to our clinic because of a second orifice posterior to the true anus. On
      the physical examination, there was a 3 mm in diameter orifice, about 0.5 cm
      behind the anus, at 6 o'clock direction on the lithotomy position. Duplicated
      lumen was checked with a metal catheter; it was about 2 cm in length ending
      blindly without connection to the rectum. A prediagnosis of ACD was made and the
      patient was operated. Duplicated segment was excised totally. Postoperative
      course was uneventful. CASE 2: One-year-old girl was referred to our clinic
      because of the same complaint. On the physical examination, there was a 2 mm in
      diameter orifice, about 0.3 cm behind the anus, at 6 o'clock direction on
      lithotomy position. Duplicated lumen was checked with a metal catheter; it was
      about 1.5 cm in length ending blindly without connection to the rectum.
      CONCLUSION: ACD is a rare congenital intestinal anomaly located posterior to the
      anus. It can be confused with other types of anorectal pathologies, such as
      hemorrhoids, fistula-in-ano, and perianal abscess at the time of diagnosis.
      Although ACD is often asymptomatic, it should be removed surgically because of
      the risk of inflammatory complications and colloidal cancer.

PMID- 19856188
TI  - Arterial distensibility is reduced in overweight pre- and early pubescent
      children.
AB  - The objective of this study was to examine the differences in arterial
      distensibility between overweight/obese and normal weight pre- and early
      pubescent boys and girls. Arterial distensibility was measured in 65 children (43
      normal weight and 22 overweight/obese) between the ages of 9 and 12 years. Weight
      classification was based on age and sex-specific body mass index (BMI) cut-offs
      and pubertal maturation by Tanner staging. Distensibility was determined using B
      Mode echo-Doppler ultrasound to measure changes in the right common carotid
      artery (CCA) diameter, while carotid pulse pressure was measured at the left CCA
      by applanation tonometry. Accounting for age and sex (ANCOVA), CCA distensibility
      showed a significant difference (P < 0.05) between normal weight (0.79 +/- 0.21)
      and overweight children (0.61 +/- 0.21 mmHg(-1) x 10(-2)). Univariate analysis
      revealed that CCA distensibility was related to BMI, systolic blood pressure,
      brachial pulse pressure, and relative oxygen uptake (VO(2peak), milliliter per
      kilogram per minute). Multivariate analysis revealed that, when adjusting for
      brachial pulse pressure and relative VO(2peak), differences in CCA distensibility
      by BMI were no longer significant. This study demonstrates that attenuated
      arterial distensibility exists in overweight pre- and early pubescent children.
      As well, this study highlights the influential role of blood pressure and aerobic
      fitness on arterial distensibility.

PMID- 19856189
TI  - Diversity of the Ty-1 copia retrotransposon Tos17 in rice (Oryza sativa L.) and
      the AA genome of the Oryza genus.
AB  - Retrotransposons are mobile genetic elements, ubiquitous in Eukaryotic genomes,
      which have proven to be major genetic tools in determining phylogeny and
      structuring genetic diversity, notably in plants. We investigate here the
      diversity of the Ty1-copia retrotransposon Tos17 in the cultivated rice of Asian
      origin (Oryza sativa L.) and related AA genome species of the Oryza genus, to
      contribute understanding of the complex evolutionary history in this group of
      species through that of the element in the lineages. In that aim, we used a
      combination of Southern hybridization with a reverse transcriptase (RT) probe and
      an adapter-PCR mediated amplification, which allowed the sequencing of the
      genomic regions flanking Tos17 insertions. This analysis was carried out in a
      collection of 47 A-genome Oryza species accessions and 202 accessions of a core
      collection of Oryza sativa L. representative of the diversity of the species. Our
      Southern hybridization results show that Tos17 is present in all the accessions
      of the A-genome Oryza species, except for the South American species O.
      glumaepatula and the African species O. glaberrima and O. breviligulata. In O.
      sativa, the number of putative copies of Tos17 per accession ranged from 1 to 11
      and multivariate analysis based on presence/absence of putative copies yielded a
      varietal clustering which is consistent with the isozyme classification of rice.
      Adapter PCR amplification and sequencing of flanking regions of Tos17 insertions
      in A-genome species other than O. sativa, followed by anchoring on the Nipponbare
      genome sequence, revealed 13 insertion sites of Tos17 in the surveyed O.
      rufipogon and O. longistaminata accessions, including one shared by both species.
      In O. sativa, the same approach revealed 25 insertions in the 6 varietal groups.
      Four insertion sites located on chromosomes 1, 2, 10, and 11 were found
      orthologous in O. rufipogon and O. sativa. The chromosome 1 insertion was also
      shared between O. rufipogon and O. longistaminata. The presence of Tos17 at three
      insertion sites was confirmed by retrotransposon-based insertion polymorphism
      (RBIP) in a sample of O. sativa accessions. The first insertion, located on
      chromosome 3 was only found in two japonica accessions from the Bhutan region
      while the second insertion, located on chromosome 10 was specific to the varietal
      groups 1, 2, and 5. The third insertion located on chromosome 7 corresponds to
      the only insertion shown active in rice so far, notably in cv. Nipponbare, where
      it has been extensively used for insertion mutagenesis. This copy was only found
      in a few varieties of the japonica group 6 and in one group 5 accession. Taken
      together, these results confirm that Tos17 was probably present in the ancestor
      of A-genome species and that some copies of the element remained active in some
      Oryza lineages--notably in O. rufipogon and O. longistaminata--as well as in the
      indica and japonica O. sativa L. lineages.

PMID- 19856190
TI  - C1 lateral mass screw-induced occipital neuralgia: a report of two cases.
AB  - C1-2 polyaxial screw-rod fixation is a relatively new technique. While
      recognizing the potential for inadvertent vertebral artery injury, there have
      been few reports in the literature outlining all the possible complications. Aim
      of this study is to review all cases of C1 lateral mass screws insertion with
      emphasis on the evaluation of potential structures at risk during the procedure.
      We retrospectively reviewed all patients in our unit who had C1 lateral mass
      screw insertion over a 2-year period. The C1 lateral mass screw was inserted as
      part of an atlantoaxial stabilization or incorporated into a modular
      occiput/subaxial construct. Outcome measures included clinical and radiological
      parameters. Clinical indicators included age, gender, neurologic status, surgical
      indication and the number of levels stabilized. Intraoperative complications
      including blood loss, vertebral artery injury or dural tears were recorded.
      Postoperative pain distribution and neurological deficit were recorded.
      Radiological indicators included postoperative plain radiographs to assess
      sagittal alignment and to check for screw malposition or construct failure. A
      total of 18 lateral mass screws were implanted in 9 patients. There were three
      male and six female patients who had C1 lateral mass screw insertion in this
      unit. Two patients had atlantoaxial stabilization for C2 fracture. There were
      four patients with rheumatoid arthritis whose C1 lateral mass screws were
      inserted as part of an occipitocervical or subaxial cervical stabilization. There
      was no vertebral artery injury, no cerebrospinal fluid leak and minimal blood
      loss in all patients. Three patients developed postoperative occipital neuralgia.
      This neuralgia was transient, in one of the patients having settled at 6-week
      follow-up. In the other two patients the neuralgia was unresolved at time of
      latest follow-up but was adequately controlled with appropriate pain management.
      Postoperatively no patient had radiographic evidence of construct failure and all
      demonstrated excellent sagittal alignment. It has been reported that the absence
      of threads on the upper portion of the long shank screw may protect against
      neural irritation. However, insertion of the C1 lateral mass screw necessitates
      careful caudal retraction of the C2 dorsal root ganglion. The insertion point for
      the C1 lateral mass screw is at the junction of the C1 posterior arch and the
      midpoint of the posterior inferior part of the C1 lateral mass. Two patients in
      our series suffered occipital neuralgia post-insertion of C1 lateral mass screws.
      This highlights the potential for damage to the C2 nerve root during C1 lateral
      mass screw placement.

PMID- 19856191
TI  - Human copper transporter Ctr1 is functional in Drosophila, revealing a high
      degree of conservation between mammals and insects.
AB  - Living cells have to carefully control the intracellular concentration of trace
      metals, especially of copper, which is at the same time essential but owing to
      its redox activity can also facilitate generation of reactive oxygen species.
      Mammals have two related copper transporters, Ctr1 and Ctr2, with Ctr1 playing
      the major role. The fruit fly Drosophila has three family members, termed Ctr1A,
      Ctr1B, and Ctr1C. Ctr1A is expressed throughout development, and a null mutation
      causes lethality at an early stage. Ctr1B ensures efficient copper uptake in the
      intestinal tract, whereas Ctr1C is mainly expressed in male gonads. Ectopic
      expression of Ctr1 transporters in Drosophila causes toxic effects due to
      excessive copper uptake. Here, we compare the effects of human Ctr1 (hCtr1) with
      those of the Drosophila homologs Ctr1A and Ctr1B in two overexpression assays.
      Whereas the overexpression of Drosophila Ctr1A and Ctr1B results in strong
      phenotypes, expression of hCtr1 causes only a very mild phenotype, indicating a
      low copper-import efficiency in the Drosophila system. However, this can be
      boosted by coexpressing the human copper chaperone CCS. Surprisingly, hCtr1
      complements a lethal Ctr1A mutation at least as well as Ctr1A and Ctr1B
      transgenes. These findings reveal a high level of conservation between the
      mammalian and insect Ctr1-type copper importers, and they also demonstrate that
      the Drosophila Ctr1 proteins are functionally interchangeable.

PMID- 19856192
TI  - Site-directed fragment-based generation of virtual sialic acid databases against
      influenza A hemagglutinin.
AB  - In this study fragment-based drug design is combined with molecular docking
      simulation technique, to design databases of virtual sialic acid (SA) analogues
      with new substitutions at C2, C5 and C6 positions of SA scaffold. Using spaces
      occupied by C2, C5 and C6 natural moieties of SA when bound to hemagglutinin (HA)
      crystallographic structure, new fragments that are commercially available were
      docked independently in all the pockets. The oriented fragments were then
      connected to the SA scaffold with or without incorporation of linker molecules.
      The completed analogues were docked to the whole SA binding site to estimate
      their binding conformations and affinities, generating three databases of HA
      bound SA analogues. Selected new analogues showed higher estimated affinities
      than the natural SA when tested against H3N2, H5N1 and H1N1 subtypes of influenza
      A. An improvement in the binding energies indicates that fragment-based drug
      design when combined with molecular docking simulation is capable to produce
      virtual analogues that can become lead compound candidates for anti-flu drug
      discovery program.

PMID- 19856193
TI  - A Saccharomyces cerevisiae-based bioassay for assessing pesticide toxicity.
AB  - This study evaluates the toxic effect of three pesticides (Azoxystrobin,
      Cymoxanil, and Diuron) on the yeast Saccharomyces cerevisiae for the development
      of a new bioassay based on inhibition of S. cerevisiae metabolic activity at the
      level of adenosine-5-triphosphate (ATP) synthesis, as compared with two different
      toxicity tests based on inhibition of Daphnia magna mobility (NF EN ISO 6341) and
      inhibition of Vibrio fisheri activity (NF EN ISO 11348). The S. cerevisiae
      bioassay is cheaper and 96 times faster than the D. magna toxicity bioassay, but
      has lower sensitivity. It is as fast as the V. fisheri bioassay and more
      sensitive. Thus, this new toxicity test can be proposed for rapid detection of
      pesticide residues in environmental samples as a complement to the more expensive
      and time-consuming D. magna toxicity test.

PMID- 19856194
TI  - Plant stanol esters lower serum triacylglycerol concentrations via a reduced
      hepatic VLDL-1 production.
AB  - Plant stanol esters not only lower low density lipoprotein cholesterol but also
      have previously been shown to lower serum triacylglycerol (TAG) concentrations,
      especially in subjects with elevated TAG concentrations. To find a possible
      explanation, we explored changes in serum lipoprotein profiles, as measured with
      nuclear magnetic resonance. For this, serum samples from two parallel-designed
      controlled studies were evaluated before and 8 weeks after the consumption of
      plant stanol esters. In the first study, dyslipidemic metabolic syndrome subjects
      participated and in the second study normolipidemic subjects. In metabolic
      syndrome subjects, plant stanol esters lowered concentrations of large (>60 nm)
      and medium (35-60 nm) VLDL particles as compared to controls. In normolipidemic
      subjects, the serum concentration of large VLDL-1 particles was also lowered,
      although less pronounced. Based on these findings, we hypothesize that the effect
      of plant stanol esters on serum TAG concentrations origins from a lowered hepatic
      production of large TAG-rich VLDL-1 particles.

PMID- 19856195
TI  - Orthopedic management of spina bifida. Part I: hip, knee, and rotational
      deformities.
AB  - Children with spina bifida develop a wide variety of congenital and acquired
      orthopedic deformities. Among these are hip deformities such as contracture,
      subluxation, or dislocation. Patients may also have problems with the knee joint,
      such as knee flexion or extension contracture, knee valgus deformity, or late
      knee instability and pain. In addition, rotational deformities of the lower
      extremities, either internal or external torsion, are common as well. This paper
      will review both the overall orthopedic care of a patient with spina bifida and
      provide a focused review of the diagnosis and management of the above
      deformities. In addition, this paper will review the incidence, etiology,
      classification, and prognosis of spina bifida. The use of gait analysis and
      orthoses will be covered as well. The forthcoming Part II will cover foot and
      ankle deformities in spina bifida.

PMID- 19856196
TI  - Gender differences in patients with acute ST-elevation myocardial infarction
      complicated by cardiogenic shock.
AB  - INTRODUCTION: The aim of our analysis is to assess gender differences in baseline
      characteristics, acute therapies, and clinical outcome in patients with acute ST
      elevation myocardial infarction (STEMI) complicated by cardiogenic shock.
      METHODS: The Maximal Individual Therapy of Acute Myocardial Infarction PLUS
      registry (MITRA PLUS) is a German prospective, multicenter, observational data
      pool of current treatment of STEMI. RESULTS: STEMI was more often (P < 0.0001)
      complicated by cardiogenic shock in female patients (12.9%) when compared to male
      patients (9.3%). This was still true after adjusting for confounding variables
      (OR 1.19, 95% CI 1.09-1.30). Women with STEMI admitted in a cardiogenic shock
      were older (P < 0.0001) and had more often concomitant diseases (P < 0.0001).
      There was no differences in rates of reperfusion therapy (OR 0.92, 95% CI 0.77
      1.09). Hospital mortality was 67.7% in female patients, when compared to 57.2% in
      male patients (P < 0.0001). After adjusting for confounding variables in the
      multivariate analysis hospital mortality did not differ between men and women (OR
      1.16, 95% CI 0.98-1.38). Early reperfusion therapy was associated with a
      significant reduction of hospital mortality in female patients with STEMI
      complicated by cardiogenic shock (OR 0.68, 95% CI 0.52-0.90) with primary PCI
      being more effective than thrombolytic therapy (OR 0.46, 95% CI 0.31-0.68).
      CONCLUSION: In women, STEMI was more often complicated by cardiogenic shock when
      compared to men. However, the use of early reperfusion therapy did not differ
      between the sexes. Primary PCI was associated with the best outcome in female
      patients with STEMI complicated by cardiogenic shock and is therefore the therapy
      of choice.

PMID- 19856197
TI  - Long chain saturated fatty acids increase haptoglobin gene expression in C57BL/6J
      mice adipose tissue and 3T3-L1 cells.
AB  - BACKGROUND: Dietary lipids are directly related to the composition of adipose
      tissue, aetiology of obesity and arousal of obesity-related pathologies, like
      chronic inflammation states. Haptoglobin is an acute phase protein secreted by
      the liver and white adipose tissue, and its blood levels vary according to the
      volume of fat in the body. AIM OF THE STUDY: To investigate the effect of diets
      enriched with large amounts of dietary fats, which differ in their fatty acid
      composition, on the haptoglobin gene expression by visceral and subcutaneous
      adipose tissue of mice fed for 2 days or 8 weeks. 3T3-L1 cells were treated with
      fatty acids that are found in those types of dietary fats. METHODS: Mice were
      treated acutely (for 2 days) or chronically (for 8 weeks) with diets enriched
      with soybean oil, fish oil, coconut oil or lard. 3T3-L1 cells were treated with
      six different fatty acids. Haptoglobin gene expression was quantified by northern
      blotting. RESULTS: Both chronic and acute treatment with lard, which is rich in
      long chain saturated fatty acids, increased the haptoglobin mRNA expression in
      the retroperitoneal and epidydimal white adipose tissues. Chronic treatment with
      coconut oil, which is rich in medium chain saturated fatty acids, increased the
      haptoglobin expression in the epidydimal and subcutaneous depots. In 3T3-L1,
      palmitic acid increased the haptoglobin gene expression. CONCLUSION: The type of
      lipids in the diet can differently modulate the white adipose tissue gene
      expression of haptoglobin, and saturated fatty acids play a major role in
      promoting a pro-inflammatory environment. This response is fat pad specific and
      dependant on the duration of treatment.

PMID- 19856198
TI  - MRI study of the cavum septum pellucidum in obsessive-compulsive disorder.
AB  - The cavum septum pellucidum (CSP), a putative marker of neurodevelopmental
      anomaly, has been associated with an increased risk of several psychiatric
      disorders. The purpose of this study was to evaluate the CSP in patients with
      obsessive-compulsive disorder (OCD) compared with healthy control subjects.
      Seventy-one patients with OCD and 71 healthy volunteers matched for age and sex
      were evaluated with magnetic resonance imaging. We evaluated the CSP using
      criteria employed in previous studies: presence of the CSP, length of the CSP,
      and overall size of the CSP, measured in five grades, ranging from grades 0 (no
      CSP) to 4 (severe CSP). We evaluated OCD symptom severity using the Yale-Brown
      Obsessive-Compulsive Scale (Y-BOCS). The CSP presence was significantly greater
      in the OCD group (60.6%) than in control subjects (29.6%), and CSP size grade was
      significantly larger in the OCD group (chi(2) = 15.609, P = 0.004). CSP length
      showed no significant group difference. Among patients with OCD, those with a CSP
      had higher scores on the obsession subscale of the Y-BOCS than those without a
      CSP (Z = -2.358, P = 0.018), while they did not show significant difference from
      those without a CSP in the compulsion subscale of the Y-BOCS, age, duration of
      illness, or age at onset. These results indicate that neurodevelopmental
      alterations in midline structures might contribute to the pathogenesis of OCD.

PMID- 19856199
TI  - Plasma calprotectin in chronically dialyzed end-stage renal disease patients.
AB  - OBJECTIVE: The current study aimed to evaluate plasma calprotectin levels and
      clearance end-stage renal disease (ESRD) patients with and without acute
      infection undergoing chronic hemodialysis (HD). MATERIALS AND METHODS: Blood
      samples from 54 HD patients were obtained before and after the HD and 42 healthy
      blood donors were examined as controls. The blood levels of calprotectin,
      procalcitonin, C-reactive protein (CRP), and intracellular production of
      interleukins 10 and 12 in monocytes were determined in both groups. RESULTS: The
      concentrations of plasma calprotectin in ESRD patients were significantly higher
      than in healthy controls (p < 0.05). No differences between pre- and post-HD
      calprotectin plasma levels were observed (p = 0.07 for two-tailed test). Plasma
      calprotectin levels were not significantly influenced by the presence of acute
      infection (p = 0.19) or diabetes (p = 0.42). A significant positive correlation
      of plasma calprotectin to plasma beta-2 microglobulin was proven (p < 0.05).
      Procalcitonin (PCT), CRP, IL-10, and IL-12 were not correlated with plasma
      calprotectin before or after HD. The elevation of plasma calprotectin was
      correlated strongly to the hemodialysis vintage (r = 0.55, p < 0.01).
      CONCLUSIONS: Significantly elevated levels of plasma calprotectin in ESRD
      patients occur without an acute infectious cause and are not affected by the
      presence of diabetes. By analogy to plasma beta-2 microglobulin, a close relation
      of plasma calprotectin to HD vintage was shown.

PMID- 19856200
TI  - 3D environment on human mesenchymal stem cells differentiation for bone tissue
      engineering.
AB  - In this work a novel method was developed to create a three dimensional
      environment at a cellular level for bone tissue engineering. Biphasic calcium
      phosphate (BCP) particles of 140-200 microm were used in association with human
      mesenchymal stem cells (hMSCs). The cells seeded on these particles adhered and
      proliferated more rapidly in the first day of culture compared to culture on
      plastic. Analyses of hMSCs cultured without osteogenic factors on BCP particles
      revealed an abundant extracellular matrix production forming 3-dimensional (3D)
      hMSCs/BCP particles constructs after few days. Bone morphogenetic 2 (BMP-2), bone
      sialoprotein (BSP) and ALP gene expression using real time quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) confirmed that expression
      profiles were modified by the culture substrate while the addition of osteogenic
      medium enhanced bone markers expression. These results indicate that BCP
      particles alone are able to induce an osteoblastic differentiation of hMSCs that
      might be of interest for bone tissue engineering.

PMID- 19856201
TI  - Integrin and chemokine receptor gene expression in implant-adherent cells during
      early osseointegration.
AB  - The mechanisms of early cellular recruitment and interaction to titanium implants
      are not well understood. The aim of this study was to investigate the expression
      of pro-inflammatory cytokines, chemokines and adhesion markers during the first
      24 h of implantation. Anodically oxidized and machined titanium implants were
      inserted in rat tibia. After 3, 12, and 24 h the implants were unscrewed and
      analyzed with quantitative polymerase chain reaction. Immunohistochemistry and
      scanning electron microscopy revealed different cell types, morphology and
      adhesion at the two implant surfaces. A greater amount of cells, as indicated by
      higher expression of small subunit ribosomal RNA (18S), was detected on the
      oxidized surface. Higher expression of CXC chemokine receptor-4 (at 12 h) and
      integrins, alphav (at 12 h), beta1 (at 24 h) and beta2 (at 12 and 24 h) was
      detected at the oxidized surfaces. Significantly higher tumor necrosis factor
      alpha (at 3 h) and interleukin-1beta (at 24 h) expression was demonstrated for
      the machined surface. It is concluded that material surface properties rapidly
      modulate the expression of receptors important for the recruitment and adhesion
      of cells which are crucial for the inflammatory and regenerative processes at
      implant surfaces in vivo.

PMID- 19856202
TI  - Adherence is a multi-dimensional construct in the POUNDS LOST trial.
AB  - Research on the conceptualization of adherence to treatment has not addressed a
      key question: Is adherence best defined as being a uni-dimensional or multi
      dimensional behavioral construct? The primary aim of this study was to test which
      of these conceptual models best described adherence to a weight management
      program. This ancillary study was conducted as a part of the POUNDS LOST trial
      that tested the efficacy of four dietary macronutrient compositions for promoting
      weight loss. A sample of 811 overweight/obese adults was recruited across two
      clinical sites, and each participant was randomly assigned to one of four
      macronutrient prescriptions: (1) Low fat (20% of energy), average protein (15% of
      energy); (2) High fat (40%), average protein (15%); (3) Low fat (20%), high
      protein (25%); (4) High fat (40%), high protein (25%). Throughout the first 6
      months of the study, a computer tracking system collected data on eight
      indicators of adherence. Computer tracking data from the initial 6 months of the
      intervention were analyzed using exploratory and confirmatory analyses. Two
      factors (accounting for 66% of the variance) were identified and confirmed: (1)
      behavioral adherence and (2) dietary adherence. Behavioral adherence did not
      differ across the four interventions, but prescription of a high fat diet (vs. a
      low fat diet) was found to be associated with higher levels of dietary adherence.
      The findings of this study indicated that adherence to a weight management
      program was best conceptualized as being multi-dimensional, with two dimensions:
      behavioral and dietary adherence.

PMID- 19856203
TI  - Prayer and reverence in naturalistic, aesthetic, and socio-moral contexts
      predicted fewer complications following coronary artery bypass.
AB  - This prospective study explores prayer, reverence, and other aspects of faith in
      postoperative complications and hospital length of stay of patients undergoing
      coronary artery bypass graft surgery. Alongside traditional religiousness
      measures, we examined sense of reverence in religious and secular contexts. Face
      to-face interviews were conducted with 177 patients 2 weeks before surgery at a
      medical center. Medical variables were retrieved from the national Society of
      Thoracic Surgeons' Database. Logistic and multiple regression models were
      performed to predict outcomes. Prayer frequencies were associated with reduced
      complications but not hospitalization. Sense of reverence in secular contexts
      predicted fewer complications and shorter hospitalization. Controlling for
      complications reduced the initial influence of reverence on hospitalization,
      suggesting the potential mediation of complications. No interaction between
      demographics and faith factors was evident. The role of faith in medicine is
      complex and context-dependent. Future studies are needed on mediating factors.

PMID- 19856205
TI  - Cyclosporine A reduces dendritic outgrowth of neuroblasts in the subgranular zone
      of the dentate gyrus in C57BL/6 mice.
AB  - In the present study, we observed the effects of cyclosporine A (CsA), an
      efficient immunosuppressant, on cell proliferation and neuroblast differentiation
      in the subgranular zone of the dentate gyrus (SZDG) in normal C57BL/6 mice using
      Ki67 and doublecortin (DCX) immunohistochemical staining, respectively. At 8
      weeks of age, vehicle (physiological saline) or CsA was daily administered (40
      mg/kg, i.p.) for 1 week. Animals were sacrificed at 2 weeks after last
      administration. CsA treatment did not show any influences in neurons, astrocytes
      and microglia based on immunohistochemistry for its markers, respectively.
      However, in the CsA-treated group, Fluoro-Jade B, a marker for neurodegeneration,
      positive cells were found in the SZDG, not in the vehicle-treated group. In the
      vehicle-treated group, Ki67 immunoreactive (+) nuclei were clustered in the SZDG,
      whereas in the CsA-treated group Ki67(+) nuclei were scattered in the SZDG,
      showing no difference in cell numbers. Numbers of DCX(+) neuroblasts with well
      developed processes (tertiary dendrites) were much lower in the CsA-treated group
      than those in the vehicle-treated group; however, numbers of DCX(+) neuroblasts
      with secondary dendrites were similar in both the groups. These results suggest
      that CsA significantly reduces dendritic outgrowth and complexity from
      neuroblasts in the SZDG without any affecting in neurons, astrocytes and
      microglia in normal mice.

PMID- 19856207
TI  - Apoptosis in diabetes.

PMID- 19856206
TI  - Cellular elements of the blood-brain barrier.
AB  - The Blood-brain-barrier (BBB) provides both anatomical and physiological
      protection for the central nervous system (CNS), shielding the brain for toxic
      substances in the blood, supplying brain tissues with nutrients and filtering
      harmful compounds from the brain back to the bloodstream. The BBB is composed of
      four main cellular elements: endothelial cells (ECs), astrocyte end-feet,
      microglial cells, and pericytes. Transport across the BBB is limited by both
      physical and metabolic barriers (enzymes, and different transport systems). Tight
      junctions (TJs) present between ECs form an important barrier against diffusion,
      excluding most blood-borne substances for entering the brain.

PMID- 19856208
TI  - Maternal overweight and smoking: prenatal risk factors for caries development in
      offspring during the teenage period.
AB  - This study aimed to investigate pre- and perinatal determinants as risk factors
      for caries development in offspring. In this longitudinal register-based cohort
      study, we included all children (n = 18,142), of 13 years of age who resided in
      the county of Stockholm, Sweden, in 2000. The cohort was followed until
      individuals were 19 years of age. In total, 15,538 subjects were examined. Dental
      caries (decayed, missing and filled teeth/surfaces), were collected from the
      Public Health Care Administration in Stockholm. Data concerning pre- and
      perinatal factors, as well as parental socio-demographic determinants, were
      collected from the Swedish Medical Birth Register and Swedish National Registers
      at Statistics Sweden. Mean approximal caries increment (DMFSa) was 1.34 +/- 2.74.
      The results showed that the prenatal factors, "maternal smoking" and "maternal
      overweight" exhibited an increased risk of approximal caries increment, (OR 1.33;
      95% CI = 1.22-1.44) and (OR 1.21; 95% CI = 1.07-1.37), respectively. Concerning
      maternal overweight, the excess risk enhanced in relation to the magnitude of the
      caries increment and maternal smoking was significant across the various DMFSa
      outcome cut-off levels. In conclusion, this study demonstrates that the prenatal
      factors, maternal overweight, as well as smoking, are risk factors for approximal
      caries development in offspring during the teenage period.

PMID- 19856209
TI  - Effect of nutritional status and sampling intensity on recovery after dorsal
      aorta cannulation in free-swimming Atlantic salmon (Salmo salar L.).
AB  - Recovery from implantation of a cannula in the dorsal aorta (DA) of Atlantic
      salmon (Salmo salar) was studied in relation to nutritional status and sampling
      intensity. The incentive for the study was the inconsistency between published
      reports and our own experience of recovery and longevity of fish exposed to this
      protocol. In two studies using starved fish, blood (0.3 ml) was sampled 0, 1 and
      24 h after DA-cannulation, and thereafter at 48 and 72 h and thereafter once
      weekly for four weeks. In a third study using fed fish, four consecutive samples
      (0, 3, 6 and 12 h after a meal) were obtained twice a week over a four-week
      period. All fish displayed a sharp increase in pCO(2) and haematocrit (Hct)
      during surgery, followed by a marked raise in cortisol, glucose, sodium and
      potassium (1 h). pCO(2), pH and Hct approached baseline levels as early as the 1
      h post-surgery sample, while this was not the case for cortisol and electrolytes
      before the 24 h post-surgery sample. Glucose did not display any significant
      changes post surgery. From then on, all variables displayed minor but non
      significant (P > 0.05) changes indicating a steady state close to baseline values
      for unstressed fish. This pattern was independent of sampling procedure, i.e.
      repeated single or multiple samples and thus volume of blood removed. Nutritional
      status (fed vs. starved) did not affect post-surgical recovery pattern. Only K(+)
      and Hct displayed consistent and significant post-prandial patterns. We found
      marked differences between baseline level of cannulated fish and uncannulated
      control fish, in pH, K(+) and Hct indicating that cannulation may be the
      preferred method to obtain representative resting values in fish.

PMID- 19856210
TI  - About "Origin and evolution of the free radical theory of aging: a brief personal
      history, 1954-2009".

PMID- 19856211
TI  - Criticality in a non-equilibrium, driven system: charged colloidal rods (fd
      viruses) in electric fields.
AB  - Experiments on suspensions of charged colloidal rods (fd-virus particles) in
      external electric fields are performed, which show that a non-equilibrium
      critical point can be identified. Several transition lines of field-induced
      phases and states meet at this point and it is shown that there is a length- and
      time-scale which diverge at the non-equilibrium critical point. The off-critical
      and critical behavior is characterized, with both power law and logarithmic
      divergencies. These experiments show that analogous features of the classical,
      critical divergence of correlation lengths and relaxation times in equilibrium
      systems are also exhibited by driven systems that are far out of equilibrium,
      related to phases/states that do not exist in the absence of the external field.

PMID- 19856212
TI  - Avian flu pandemic - flight of the healthcare worker?
AB  - BACKGROUND: One of the ethical issues identified in response to a possible
      pandemic is healthcare workers' duty to provide care during a communicable
      disease outbreak. Healthcare employees may be subject to a variety of work
      obligations under such conditions. Questions of duty to treat remain
      controversial, and debate continues as to the ethical articulation of a duty to
      treat. This study aimed to investigate opinions from healthcare workers
      themselves on the perceived duty to treat, and how they might respond to a severe
      avian flu pandemic. METHODS: Using system-wide e-mail, we surveyed employees at
      our rural tertiary/quaternary care health system regarding their knowledge of our
      institution's pandemic planning policy and their willingness to work in the event
      of a virulent avian pandemic. RESULTS: Results (N=908) show that employees felt a
      responsibility for"duty to care." Over 60% disagreed that it was ethical to
      abandon the workplace during a pandemic. However, opinions also stated that
      employees wanted autonomy to decide whether or not to work (65%). When asked
      about volunteering, 79% would agree to volunteer, given some incentives and
      protective options, the most salient being protective equipment (with relative
      training for use) and infectious disease training. CONCLUSIONS: Our research
      demonstrated that the healthcare workers a tour institution voiced an earnest
      willingness to work in the event of an avian flu pandemic, if provided with the
      necessary input, protections and tools, and education. The use of an electronic
      methodology for dissemination of surveys allowed the low-cost solicitation of
      information from a vast proportion of the workforce with ease, providing the
      institutional ethics committee with the empirical data needed to articulate more
      meaningful,thoughtful, and robust suggestions for ethical pandemic planning.

PMID- 19856213
TI  - Effect of focal adhesion proteins on endothelial cell adhesion, motility and
      orientation response to cyclic strain.
AB  - Focal adhesion proteins link cell surface integrins and intracellular actin
      stress fibers and therefore play an important role in mechanotransduction and
      cell motility. When endothelial cells are subjected to cyclic mechanical strain,
      time-lapse imaging revealed that cells underwent significant morphological
      changes with their resultant long axes aligned away from the strain direction. To
      explore how this response is regulated by focal adhesion-associated proteins the
      expression levels of paxillin, focal adhesion kinase (FAK), and zyxin were
      knocked down using gene silencing techniques. In addition, rescue of endogenous
      and two mutant zyxins were used to investigate the specific role of zyxin
      interactions. Cells with decreased zyxin expression levels and rescue with the
      mutant lacking zyxin/alpha-actinin binding exhibited lower orientation angles
      after comparable times of stretching as compared to normal and control cells.
      However, knockdown of the expression levels of paxillin and FAK and rescue with
      the mutant lacking zyxin/VASP (vasodilator-stimulated phosphoprotein) binding did
      not significantly affect the degree of cell orientation. In addition, wound
      closure speed and cell-substratum adhesive strength were observed to be
      significantly reduced only for cells with zyxin depletion and the mutation
      lacking zyxin/alpha-actinin binding. These results suggest that zyxin and its
      interaction with alpha-actinin are important in the regulation of endothelial
      cell adhesive strength, motility and orientation response to mechanical
      stretching.

PMID- 19856214
TI  - Mouse models of CNS embryonal tumors.
AB  - Central nervous system (CNS) embryonal tumors are devastating cancers in
      children, consisting of medulloblastomas, CNS primitive neuroectodermal tumors,
      and atypical teratoid/rhabdoid tumors. One of the reasons that CNS embryonal
      tumors remain difficult to treat is their rarity, which makes conducting clinical
      trials for these tumors difficult. Recent advances of molecular biology have led
      us to identify molecular and genetic causality of brain tumors. Based on the
      genetic alterations found in humans, multiple models of human CNS embryonal
      tumors have been generated in genetically engineered mice. These mouse models are
      valuable tools for understanding brain tumor biology and discovering novel
      therapeutic targets and drugs. In this article, we review molecular and
      cytogenetic characteristics of human CNS embryonal tumors and corresponding mouse
      models that have been developed. These findings indicate that common genetic
      abnormalities are seen in variants of human CNS embryonal tumors, and multiple
      histological variants of these tumors can be generated from a single set of
      genetic abnormalities in mice. These data provide insight into the biology and
      classification of CNS embryonal tumors.

PMID- 19856216
TI  - Radiopathological characteristics of cerebellar malignant glioma in adults.
AB  - Our aim was to extract the radiopathological features of cerebellar malignant
      glioma in adults from the four cases we encountered. All four cases (two men and
      two women, aged 52-80 years; mean age, 67 years) had a floating sensation or
      vertigo at the onset of their disease. Initially, these patients were given a
      diagnosis of cerebellar infarction or cavernous angioma, or had faint
      abnormalities in the cerebellum that were overlooked. These patients were
      followed up for 2-14 months (mean, 6 months), and the tumor was detected when
      their clinical symptoms deteriorated. The tumor was located in the hemisphere in
      one patient and in the vermis in three patients. MRI revealed ring-like
      enhancement in two patients and nodular enhancement in two patients. All patients
      underwent subtotal tumor resection, followed by postoperative radiochemotherapy.
      However, three patients died at 16 to 44 months (mean, 28 months), and
      cerebrospinal fluid (CSF) dissemination was observed in three patients. Two cases
      were classified as WHO grade III and two as WHO grade IV. The pathological
      features were typical of malignant glioma, partially presenting the features of
      low-grade glioma, such as pilocytic, astrocytic, or oligodendroglial components.
      Nuclear pleomorphism and vascular endothelial proliferation were prominent, and
      micronecrosis was relatively less evident. The MIB-1 index was 12%-40%, and most
      of the patients were p53 protein positive. At the onset of cerebellar malignant
      glioma, diagnostic imaging shows few signs of brain tumor. Thereafter, tumors
      grow in a short period of time, following a rapid clinical course. Because
      cerebellar malignant glioma is a rare disease, it is difficult to differentiate
      it from metastatic brain tumors and primary central nervous system lymphoma by
      preoperative imaging. Some patho logical features suggesting malignant
      transformation from low-grade glioma were detected.

PMID- 19856215
TI  - Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for
      counting mitotic figures in meningioma cases.
AB  - According to current World Health Organization (WHO) criteria, counting mitotic
      figures (MF), which is equal to the mitotic index (MI), on paraffin sections
      stained with hematoxylin and eosin (HE) is one of the recognized classification
      methods for meningiomas. However, it is not always easy to find the area of
      highest mitotic activity, and there are different perspectives among pathologists
      with regard to differentiating MF from non-MF, i.e., which are apoptotic figures
      and which are crushed or distorted cells. Moreover, there is an issue of
      overgrading in meningiomas with preoperative feeder embolization. Recently, anti
      phosphohistone-H3 (PHH3) antibody has been reported as a mitosis-specific marker
      for meningioma grading. In this study, we attempted PHH3 immunostaining for our
      meningioma cases and verified not only the sensitivity of PHH3 immunostaining but
      also that of its usefulness in grading meningiomas. Forty-five initial
      histologically confirmed meningiomas (37 benign, 7 atypical, and 1 anaplastic)
      were reviewed according to current WHO criteria based on counting MF on HE
      stained slides. PHH3-immunostained MF were counted in the same way, and the MIB-1
      labeling index (LI) was calculated for each sample. PHH3-labeled MF were easily
      identified and permitted rapid recognition of the areas of highest mitotic
      activity. As a result, significant increase of PHH3 mitotic index (PHH3-MI) in
      comparison with HE mitotic index (HE-MI) and strong correlations with HE-MI to
      PHH3-MI as well as PHH3-MI to MIB-1 LI were demonstrated. Furthermore, no
      significant differences of PHH3-MI between cases with and without feeder
      embolization were demonstrated. As such, PHH3 may be a sensitive and useful
      marker for meningioma grading as based on the MF.

PMID- 19856217
TI  - Recurrence and regrowth of benign meningiomas.
AB  - The World Health Organization (WHO) grading system for meningioma is helpful for
      predicting aggressive subtypes. However, even benign meningiomas sometimes show
      relatively rapid growth and may recur after total removal. We attempted to find
      histopathological features that would be valuable for predicting recurrence or
      regrowth of WHO grade I meningiomas. We investigated 135 benign meningiomas, of
      which 120 were totally removed (Simpson's grade I-III). The median follow-up
      period was 9.7 years (1-21 years). The recurrence rate in the patients with total
      removal was 7.5% at 10 years and 9.3% at 20 years. The univariate analysis
      revealed that MIB-1 index (>or=2%), existence of mitosis, absence of
      calcification, and paucity of fibrosis significantly correlated with recurrence.
      On the other hand, the histological features of sheet-like growth, prominent
      nucleoli, and necrosis did not correlate with recurrence, because they were
      relatively rare in grade I tumors. Multivariate analysis revealed that high MIB-1
      index and absence of calcification significantly correlated with recurrence. The
      patients with recurrent or residual tumors did not always receive adjuvant
      treatment. Including subtotally treated tumors, the retreatment rate was 9.8% at
      10 years and 25.6% at 20 years. MIB-1 index and Simpson's grade significantly
      correlated with retreatment in both univariate and multivariate analyses.

PMID- 19856218
TI  - Successful treatment of neoadjuvant therapy for papillary tumor of the pineal
      region.
AB  - We report a boy who in 1994, at the age of 11, presented with headache and
      vomiting. The fi nal diagnosis was papillary tumor of the pineal region (PTPR).
      Magnetic resonance imaging (MRI) revealed a heterogeneous mass. Hydrocephalus was
      addressed by immediate ventricle drainage; subsequently, we attempted tumor
      removal. As the intraoperative diagnosis of the hemorrhagic tumor was primitive
      neuroectodermal tumor (PNET), we did not proceed to total removal. After the
      delivery of radiotherapy (50.4 Gy) and one course of Nimustine hydrochloride
      (ACNU) chemotherapy, the residual tumor was completely resected. The diagnosis at
      that time (1994) was papillary pineocytoma. He was followed on an outpatient
      basis for 15 years and remained free of recurrence. This type of tumor was later
      proposed to represent a new distinct tumor subtype, papillary tumor of the pineal
      region (PTPR). Our data indicate that our patient's tumor should be included in
      this category.

PMID- 19856219
TI  - Tanycytic ependymoma of the filum terminale with pleomorphic giant cells.
AB  - A tanycytic ependymoma measuring 1.5 cm in maximal dimension, which involved the
      filum terminale and conus medullaris of a 55-year-old woman, is reported. The
      tumor consisted of a compact fascicular proliferation of spindle cells having
      long bipolar cytoplasmic processes, and immunohistochemical and ultrastructural
      studies demonstrated the ependymal features of neoplastic cells. The most
      prominent finding was an appearance of many atypical and pleomorphic, often
      monstrous, giant cells, which was not associated with an increase in
      proliferative activity. Remarkable nuclear atypism and pleomorphism with
      formation of giant cells have not been documented previously in tanycytic
      ependymoma. These nuclear changes are considered essentially degenerative in
      nature and probably do not portend a worse prognosis despite their worrisome
      appearance. This tumor could be appropriately termed "giant cell tanycytic
      ependymoma."

PMID- 19856220
TI  - Clinicopathological features from long-term observation of a papillary tumor of
      the pineal region (PTPR): a case report.
AB  - Papillary tumor of the pineal region (PTPR) was recently added to the 2007 WHO
      classification of tumors of the central nervous system as a rare pineal tumor. We
      present a case of a 17-year-old man who developed a 3-cm pineal tumor that was
      incompletely excised following two operations. The pathological findings
      presented were extensive epithelial papillary structures surrounding vessels
      mimicking "perivascular pseudo-rosettes," leading to a diagnosis of "papillary
      ependymoma." Subsequently, the residual tumor recurred on three separate
      occasions. Immunohistochemical studies showed the tumor was positive for
      cytokeratin 18 (CK 18), microtubule-associated protein (MAP 2), neuron-specific
      enolase (NSE), neuronal nuclei (NeuN), and transthyretin, consistent with mature
      neuronal differentiation. Given these findings, the diagnosis of PTPR was made.
      The patient's survival time of 218 months is the longest reported to date for
      this tumor.

PMID- 19856221
TI  - Collision tumor of anaplastic oligodendroglioma and gangliocytoma: a case report.
AB  - A 53-year-old woman presented with a rare case of coexistence of anaplastic
      oligodendroglioma with gangliocytoma manifesting as progressive disturbance of
      consciousness and left hemiparesis. Magnetic resonance imaging with gadolinium
      demonstrated the mass lesion consisted of a strongly enhanced area around the
      middle cerebral artery and less enhanced areas in the right temporal lobe,
      insula, and basal ganglia. She underwent subtotal resection of the tumor,
      resulting in improvement of her symptoms. Macroscopic and histological
      examination showed the tumor consisted of two distinct components, grayish soft
      tissue and yellowish hard tissue. The former consisted of cells with equal-sized
      round-to-oval hyperchromatic nuclei and perinuclear halo with microvascular
      proliferation and necrosis, and the diagnosis was anaplastic oligodendroglioma.
      The latter consisted of large and dysplastic neurons with marked nucleoli and
      basophilic cytoplasm containing Nissl bodies, with nonneoplastic glial cells in
      the stroma, and the diagnosis was gangliocytoma. Both lesions were distinct, but
      intermingled at the border. These two tumors apparently occurred as a collision
      tumor.

PMID- 19856222
TI  - Primary Ewing's sarcoma of the orbit: case report.
AB  - A 22-year-old man presented with tenderness and swelling of the left lateral part
      of the orbit. Computed tomography revealed a left intraorbital mass measuring 3
      cm x 3 cm involving the left lateral wall of the orbit and the greater wing of
      the left sphenoid bone. Magnetic resonance imaging revealed that the intraorbital
      mass was extraneuroaxial. During surgery, the tumor was seen to arise from the
      lateral wall of the orbit and infiltrate into the left temporal muscle. Following
      the surgery, the patient was administered radiation therapy for the whole cranium
      and chemotherapy for the residual tumors. However, the tumor recurred, and the
      patient died about 2 years following the first surgery because the tumor had
      metastasized to the lung. On light microscopy, the tumor cells were closely
      packed with uniform, small, and round cells. Immunohistochemical studies showed
      that the tumor cell membrane stained positive for MIC2. Furthermore, the MIB-1
      labeling index was 36.2%. On electron microscopy, small quantities of cytoplasm
      containing glycogen accumulations without neurosecretory granules and
      neurofilaments were observed. Based on these results, the tumor was diagnosed to
      be primary Ewing's sarcoma. Primary orbital Ewing's sarcoma of the skull has been
      considered to be extremely rare, and a review of the literature was performed.

PMID- 19856223
TI  - Film-reading ability of radiographers in detecting gastric cancer during
      screening using X-ray examination.
AB  - PURPOSE: The aim of this study was to evaluate the film-reading ability of
      radiographers in detecting gastric cancer during screening X-ray examinations.
      MATERIALS AND METHODS: A test set of 100 patients (50 negative and 50 positive;
      mean age 62 years, range 33-78 years) given a stomach X-ray examination were
      selected from those who underwent gastric cancer screening in Osaka, Japan,
      between 2000 and 2003. Eleven radiographers and four radiologists scored the test
      set on a five-point scale. A receiver operating characteristic (ROC) analysis was
      performed, and the area under the ROC curve (AUC) was defined as a measure of
      film-reading ability to detect cancer. RESULTS: No significant difference (two
      tailed P = 0.962, Welch's t-test) was observed between averaged AUC values from
      radiographers (0.76, range 0.85-0.62) and radiologists (0.75, range 0.86-0.62).
      CONCLUSION: Film-reading ability of radiographers in detecting gastric cancer
      during screening X-ray examinations was not significantly different from that of
      radiologists. Our results suggest that radiographers can assist radiologists to
      detect gastric cancer during screening.

PMID- 19856224
TI  - Effects of blood flow control on clinical outcomes after ethanolamine oleate
      sclerotherapy for vascular malformations.
AB  - PURPOSE: The purpose of this study was to assess the control of nidus blood flow
      and the association between such control and clinical outcomes after ethanolamine
      oleate (EO) sclerotherapy for vascular malformations. MATERIALS AND METHODS:
      Morphological grades on magnetic resonance (MR) images (grades 1-3), preprocedure
      nidus blood flow control, and clinical results in 22 cases of vascular
      malformation were reviewed. RESULTS: Cases were subdivided by MR morphological
      grade as follows: grade 1, 3 patients; grade 2A, 6 patients; grade 3, 13
      patients. Responses to EO sclerotherapy were as follows: excellent, 3 patients;
      good, 5 patients; poor, 14 patients. An excellent response was achieved in one
      grade 1 case, one grade 2A case, and one grade 3 case. Preprocedure nidus flow
      was controlled in 8 lesions (type A) and not controlled in 14 lesions (type B).
      Three (37.5%) type A lesions had an excellent response, five had a good response;
      and none had a poor response. All type B lesions had a poor response. Flow
      control predicted an excellent result (P < 0.05). CONCLUSION: Preprocedure nidus
      blood flow control (versus lack of control) is associated with a significantly
      higher incidence of favorable clinical responses to EO sclerotherapy for vascular
      malformations.

PMID- 19856225
TI  - Incidence of tracheobronchomalacia associated with pulmonary emphysema: detection
      with paired inspiratory-expiratory multidetector computed tomography using a low
      dose technique.
AB  - PURPOSE: The purpose of this study was to evaluate the frequency of
      tracheobronchomalacia (TBM) associated with pulmonary emphysema with paired
      inspiratory-expiratory multidetector computed tomography (MDCT) using a low-dose
      technique. MATERIALS AND METHODS: This study included 56 consecutive patients (55
      men, 1 woman; mean age 68.9 years) with pulmonary emphysema who had undergone
      paired inspiratory-expiratory CT scanning with a low-dose technique (40 mA). All
      images were retrospectively examined by two thoracic radiologists in a blinded
      fashion. The diagnosis of TBM was based on the standard criterion of >50%
      reduction in the cross-sectional area of the tracheobronchial lumen at the end
      expiratory phase. A mild TBM criterion of >30% reduction was also reviewed. All
      patients underwent pulmonary function tests. The relation between the forced
      expiratory volume in 1 s (FEV(1.0%)) and TBM was statistically analyzed. RESULTS:
      Four (7.1%) and eight (14.3%) patients were diagnosed as TBM based on the
      standard and mild criteria, respectively. In four patients, the percentages of
      luminal narrowing were 63.4% and 51.2%, respectively for tracheomalacia and 59.2%
      and 62.0%, respectively, for bronchomalacia. The FEV(1.0%) values between
      patients with and without TBM showed no statistical difference. CONCLUSION: The
      incidence of TBM associated with pulmonary emphysema was 7.1% with the standard
      criterion. It is possible that TBM has been underdiagnosed in a number of
      patients with pulmonary emphysema.

PMID- 19856226
TI  - Longitudinal practical measurement of skin color and moisture during and after
      breast-conserving therapy: influence of neoadjuvant systemic therapy.
AB  - PURPOSE: The aim of this study was to assess radiation dermatitis, especially
      exploring the influence of neoadjuvant systemic therapy (NST). MATERIALS AND
      METHODS: We examined maximum toxicity using the Common Toxicity Criteria version
      3 score (CTC v3) following radiotherapy between 40 patients treated with NST and
      59 patients without NST. In addition, objective skin color (L*, a*, b* values)
      and moisture analyses were applied in 13 NST and 25 control patients, and the
      ratio of the values for the irradiated side to the nonirradiated side was
      calculated. RESULTS: For the CTC v3 assessment, 27 grade 1 (68%) and 13 grade 2
      (32%) reactions occurred in the NST group and 44 grade 1 (75%) and 15 grade 2
      (25%) reactions in the control group. All ratios except the b* ratio showed
      significant alterations when radiotherapy was added. The ratio of the a* value
      peaked at the completion of radiotherapy, whereas the L* ratio bottomed out 1
      month later. Furthermore, moisture change remained even 1 year after treatment.
      Boost irradiation doses caused enhanced alterations in the L* and a* ratios.
      Furthermore, the L* and a* ratios had good agreement with the CTC v3 assessment.
      NST did not enhance alterations. CONCLUSION: Objective analysis is useful for
      detailed assessment of radiation dermatitis. NST did not worsen skin reactions.

PMID- 19856227
TI  - Multiple lung tumors as the cause of death in a patient with subarachnoid
      hemorrhage: postmortem computed tomography study.
AB  - A 77-year-old woman who had been in the hospital suffering from a subarachnoid
      hemorrhage suddenly died after undergoing a cerebral aneurysmal operation.
      Postmortem whole-body computed tomography (CT) demonstrated multiple lung tumors
      with abnormal masses in the bronchus with no evidence of complications in the
      cranium. The patient was estimated to have died from asphyxia caused by
      metastatic lung and endobronchial tumors. Although a traditional autopsy was not
      performed, postmortem CT provided strong evidence for detecting the cause of
      death. In this case, postmortem CT played an important role in hospital risk
      management.

PMID- 19856228
TI  - Plurifocal malignant peripheral nerve sheath tumor demonstrated by 18F
      fluorodeoxyglucose positron emission tomography/computed tomography.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas that derive from
      peripheral nerves or from cells associated with the nerve sheath. Magnetic
      resonance imaging is the main diagnostic imaging modality for evaluating MPNSTs.
      Computed tomography (CT) of the chest is the main imaging modality used to screen
      for distant disease, and bone scanning is considered useful for identifying
      selected metastases. Fluorodeoxyglucose positron emission tomography (FDG-PET)
      has been useful for differentiating malignant nerve sheath tumors from benign
      lesions and appears to be able to forecast prognosis. We report a case of a
      patient with neurofibromatosis 1 (NF1) with a histological diagnosis of MPNST,
      which was diagnosed by biopsy of a posterior right thigh mass examined by (18)F
      FDG-PET/CT.

PMID- 19856229
TI  - Hoyeraal-Hreidarsson syndrome: magnetic resonance imaging findings.
AB  - Hoyeraal-Hreidarsson syndrome (HH) has been defined as a severe variant of
      dyskeratosis congenita (DKC). We report here a case of a 6-year-old girl with HH
      who presented with bone marrow hypoplasia, skin pigmentation, nail dystrophy,
      growth retardation, and bilateral retinal hemorrhage. Brain MRI revealed
      cerebellar hypoplasia, hypoplasia of the corpus callosum, a small pituitary
      gland, a small brain stem, and focal long T2 lesions in the thalamus and brain
      stem. A brain computed tomography scan revealed intracranial calcification as
      well. To the best of our knowledge, a small pituitary gland and focal long T2
      lesions in the thalamus and brain stem have never been reported as a feature of
      HH.

PMID- 19856230
TI  - Intravenous pyogenic granuloma of the finger.
AB  - Intravenous pyogenic granuloma is a rare solitary form of lobular capillary
      hemangioma that usually occurs in the veins of the neck and upper extremities. We
      report two cases of intravenous pyogenic granuloma localized in the finger,
      giving details of the magnetic resonance imaging (MRI) findings. These two cases
      had similar locations in fingers and identical MRI findings. The differential
      diagnoses of this rare entity are also discussed.

PMID- 19856232
TI  - Attention, executive functions, and mentalizing in anorexia nervosa eighteen
      years after onset of eating disorder.
AB  - OBJECTIVE: Prospective study of attention, executive functions, and mentalizing
      abilities in a representative sample of teenage-onset anorexia nervosa (AN).
      METHOD: A total of 51 AN cases recruited after community screening were
      contrasted with 51 matched comparison cases 18 years after AN onset.
      Neuropsychological tests had been done at 21, 24, and 32 years (18 years after AN
      onset). RESULTS: The AN-group had more attention, executive function, and
      mentalizing problems. Some of these problems had been present at all three follow
      up occasions. CONCLUSIONS: AN is associated with a range of neuropsychological
      problems that are present long after the eating disorder per se is no longer an
      important feature.

PMID- 19856233
TI  - An examination of clients' in-session changes and their relationship to the
      working alliance and outcome.
AB  - The objective of the current study was to investigate the psychometric properties
      of the Client Task Specific Change Measure-Revised (CTSC-R), a measure of
      clients' in-session changes, and to determine whether the CTSC-R predicted
      outcome over and above the therapeutic alliance in a study of 66 clients treated
      with process-experiential psychotherapy or cognitive-behavioural therapy for
      depression. The measure showed high internal consistency and item-total
      correlations. Principal-axis factoring, followed by oblique rotation, showed that
      the measure comprised two factors: (a) behaviour change and (b) awareness and
      understanding. Clients' CTSC-R scores changed over the course of psychotherapy
      and predicted change in depression at the end of therapy over and above the
      therapeutic alliance, explaining an additional 13% of the variance in outcome on
      the Beck Depression Inventory. Limitations of the study and future directions for
      research are discussed.

PMID- 19856234
TI  - The efficacy of evidence-based psychotherapies versus usual care for youths:
      controlling confounds in a meta-reanalysis.
AB  - In the present meta-analysis, the authors examined how several confounding
      moderator variables may relate to the advantage of evidence-based psychological
      treatments (EBTs) over usual care (UC) in the treatment of youths, including the
      extent to which each therapy was bona fide, supervision provided to therapists,
      therapist caseload, whether EBT was provided by research therapists, and whether
      specialized training was provided for EBT therapists. When comparing EBT with
      bona fide UC while controlling for each confound individually, the advantage for
      EBT was small and nearly always statistically nonsignificant. Additionally, an
      increasing total number of confounds favoring EBT was significantly predictive of
      a greater effect size advantage for EBT. The superior efficacy of EBTs for youths
      may be an artifact of confounded research designs.

PMID- 19856235
TI  - Seeking psychological help: a comparison of individual and group treatment.
AB  - The study examined public and self-stigma and their association with attitudes
      and intentions to seek psychological help in regard to both individual and group
      treatment as well as to various subgroups, including gender, ethnicity,
      educational orientation, level of religion, and age. Undergraduate students
      (N=307) in three universities in Israel participated in the study. Results partly
      confirmed the model for both individual and group therapy: Self-stigma was
      related to attitudes and intentions to seek help. However, public stigma was not
      related to self-stigma. Importantly, some differences were also found among the
      various subgroups, and the model, which takes into account the different
      subgroups, looks somewhat different for individual and group therapy.

PMID- 19856236
TI  - Analysis of verbalized emotions in the psychotherapeutic dialogue during change
      episodes.
AB  - As described by many theorists, emotional expressions contribute to the
      activation and regulation of personal emotional experiences and communicate
      something about internal states and intentions. These emotional expressions can
      be observed in the words used in our speech and nonverbal behaviors, even when
      nonverbal behaviors are synchronized to one's own speech or to the speech of
      others. Using a quantitative and qualitative methodology, this article reports a
      classification of verbal emotional expressions of both psychotherapists and
      patients in change episodes. Assuming that the emotions loaded in linguistic
      contents are explicit emotions shown by emotion words, this methodology allows
      for a complete and differentiating assessment of affective qualities in both
      patients and psychotherapists during the psychotherapeutic dialogue.

PMID- 19856237
TI  - Effectiveness of a structured training program in psychotherapeutic skills used
      in clinical interviews for psychiatry and clinical psychology residents.
AB  - The authors evaluated a training program based on a structured manual of
      psychotherapeutic skills, using a randomized controlled design. The experimental
      group consisted of 135 residents from 12 teaching units in Spain. To control the
      improvement in therapeutic skills that could be attributed to the training
      received during the residency, the authors compared the experimental group with a
      control group of 35 residents from three teaching units. Two types of assessment
      instruments were used: a paper-and-pencil questionnaire based on clinical cases
      and a videotape of a role-playing interview. Both were given before and after the
      experimental group attended the training program. The experimental group shows a
      statistically significant improvement compared with the control group in both
      measurements.

PMID- 19856238
TI  - [Antepartal maternal risks for shoulder dystocia. An analysis of 224 744 births
      spontanous and vaginal and after the 37th week of gestation born in Hessen (2002
      2008)].
AB  - PATIENTS RESPECTIVELY AND METHODS: 224,744 vaginal and spontanous births >or= the
      37 (th) week of gestation were analysed (2002-2008) to calculate the maternal
      risks for shoulder dystocia (obesity BMI >30, high maternal weight gain >15 kg
      during pregnancy, Diabetes mellitus, Diabetes of gestation, duration of pregnancy
      >or= 298 days, multiparity >1 partus). RESULTS: It could be demonstrated for the
      first time (Degree of evidence III B), that multiparity and the weight gain>15 kg
      elevate the rate of shoulder dystocia independant of the birth weight. At a birth
      weight below 4 000 g in addition to the multiparity and the weight gain the
      obesity BMI>30 elevate significant the rate of shoulder dystocia (Degree of
      Evidence III B). In the birth weight group >or=4,000 g Diabetes mellitus elevate
      the risk of shoulder dystocia in addition to multiparity and weight gain >15 kg
      (Degree of Evidence III B). Diabetes mellitus elevate the risk of shoulder
      dystocia only in combination with macrosomia >4 000 g. CONCLUSION: The pregnant
      woman should be informed about the statistically proved different maternal risk
      factors for a shoulder dystocia and a possible paresis of the Plexus brachialis
      in relation to the fetal birth weight. The sensitivity of 60% of the sonographic
      estimation of the fetal birth weight is to low and cannot be the only content of
      an information about this danger for the newborn.

PMID- 19856239
TI  - [Paediatric brachial plexus injury--an interdisciplinary challenge to
      obstetricians, neonatologists and plexus surgeons].
AB  - Brachial plexus injuries are an interdisciplinary challenge to obstetricians,
      neonatologists and plexus surgeons. The incidence of brachial plexus injuries is
      1-4/1,000 live births, and the incidence of permanent lesions has been estimated
      to be 1/10,000 live births. Shoulder dystocia is associated with a 75-100-fold
      increase in plexus injuries. The antenatal (intrauterine) development of brachial
      plexus injuries is still a matter of controversial debate. The early recognition
      of antenatal risk factors of shoulder dystocia and its proper management by
      experienced obstetricians are mandatory; 90% of brachial plexus injuries recover
      without clinical sequelae for the newborn, however, 10% of the cases may lead to
      severe pareses requiring surgical intervention. Microsurgical nerve
      reconstruction should be performed in these cases within the first three months
      after birth. In this context, the intraoperative findings are of high prognostic
      relevance. The pathophysiology of birth-associated plexus brachialis injuries has
      been investigated in recently published experimental studies. An open dialogue
      between the specialists involved may be a great support for the parents of
      newborns suffering from plexus brachialis injuries. Medico-legal conflicts
      lasting for years should be avoided, and appropriate plexus surgical treatment by
      an experienced surgeon should be offered in good time after a careful diagnosis.

PMID- 19856240
TI  - [Prediction of shoulder dystocia--combining foetal weight estimation by
      ultrasound and maternal risk factors--a solution for the dilemma?].
AB  - BACKGROUND: Although foetal macrosomia is a known risk factor for shoulder
      dystocia, foetal weight estimation by ultrasound is imprecise. METHODS: We
      analysed in a retrospective, single-centre study whether the combination of
      foetal sonographic parameters and maternal parameters could improve the
      prediction of foetal macrosomia and whether on the basis of this findings the
      prediction of shoulder dystocia in foetal macrosomia could be enhanced.
      Likelihood ratios for sonographic parameters have been assessed and have been
      used to calculate post-test-probabilities for fetal macrosomia. All vaginal
      singleton deliveries with cephalic presentation >or=37+0 week of gestation in the
      period 1994-2005 (n=8 576) have been analysed. Shoulder dystocia has been
      observed in 136 cases (1.6%). RESULTS: In multivariate analysis the strongest
      predictor for shoulder dystocia was foetal macrosomia (>or= 4000 g), odds
      ratio=4.04 (95% confidence interval 2.71-6.05), next to diabetes 2.43 (1.14
      5.17), obesity (BMI >or=30 kg/m (2)) 1.55 (1.02-2.46), and foetal head
      circumference (>35 cm) 1.51 (1.02-2.24). Foetal sonographic parameters showed
      likelihood ratios up to 6.93. The accuracy of shoulder dystocia predictions in
      cases of birth weight >or=4,500 g improved only slightly from 0.2-3.3%.
      DISCUSSION: The accuracy of the estimation of foetal macrosomia has been improved
      by combining ultrasonography with prepartal maternal risk factors.

PMID- 19856241
TI  - [Nausea and vomiting as evolutionary mechanisms of the complex adaptation
      reaction to pregnancy].
AB  - INTRODUCTION: Nausea and vomiting during pregnancy (NVP) constitute a frequent
      and often highly unpleasant syndrome during the sensitive period of early
      pregnancy, which has been intensively investigated. However, many questions
      remain unanswered, particularly the counterintuitive association with a better
      pregnancy outcome. Under these circumstances our functional concept to interpret
      NVP as an evolutionary mechanism of complex adaptation to early pregnancy seems
      promising. METHOD: In this cross-cultural study data were collected from 565
      mothers, who had given birth recently in South Africa, Guatemala and Germany,
      using a standardised questionnaire interview. RESULTS: There was a cross
      culturally similar prevalence and clinical presentation of NVP, showing a high
      degree of subjective suffering. We found evidence supporting a multifactoral
      aetiology of biological, psychological and sociological factors. Likewise, NVP
      seems to have multiple effects, concerning nutrition, behaviour, perception,
      psychology and social support. DISCUSSION AND CONCLUSION: Our new and previously
      existing data support the idea that NVP has been selected for by evolution, as a
      functional adaptation to vulnerable early pregnancy, which benefits mother and
      child. This assumption is supported by the correlation of NVP with a better
      foetal prognosis, the cross-culturally high prevalence and a favorable relation
      of low biological costs versus high effects. The benefit of NVP could be realised
      by nutritional change, increased social support, more passive and careful
      behaviour, earlier recognition of pregnancy and a positive influence on foetal
      development. To understand the functionality of NVP, one needs to consider the
      complex somato-psychoemotional interplay in the context of an environment of
      evolutionary adaptedness (EEA).

PMID- 19856242
TI  - The influence of smoking during pregnancy on fetal growth. Considering daily
      cigarette consumption and the SGA rate according to length of gestation.
AB  - BACKGROUND: Smoking is the most important risk factor for adverse pregnancy
      outcomes in industrialized nations and is associated with, amongst other adverse
      effects, a higher rate of small-for-gestational-age (SGA) neonates. The rate of
      SGA neonates born before 32 weeks and its association with smoking have so far
      not been the focus of attention. MATERIAL AND METHODS: Using data of 643,288
      primiparous women from the German perinatal statistics of 1995-2000, we aimed to
      investigate this relationship. We also analyzed our data according to daily
      cigarette consumption. RESULTS: We found that smoking during pregnancy was
      strongly associated with lower birth weight and higher SGA rates. This effect was
      especially pronounced in women >or=31 years. There was clear dose dependence with
      regard to daily cigarette consumption. An increase in SGA rates in smokers versus
      non-smokers can already be seen for very early preterm deliveries (31 weeks of
      gestation or less). CONCLUSIONS: Our results allow the definition of groups of
      women who are at higher risk of SGA births. We show that especially older
      primiparous women (aged >or=31 years) who smoke >10 cigarettes a day are at
      increased risk of experiencing fetal growth restriction.

PMID- 19856243
TI  - [Effectiveness and safety of atosiban vs. pulsatile administration of fenoterol
      in the treatment of preterm labour].
AB  - BACKGROUND: The aim of this study was to compare the efficacy and side effects of
      atosiban with those of fenoterol (pulsatile administration) for acute tocolysis.
      METHODS: A prospective, open-label, randomised controlled trial was performed.
      Patients in preterm labour at 24+0 to 33+6 weeks of gestation were randomised to
      receive atosiban (A) or fenoterol (F) pulsatile administration. Primary outcome
      was the arrest of preterm labour. RESULTS: The proportion of woman remaining
      undelivered at 48 hours (86.3% atosiban group and 79.6% fenoterol group) and at 7
      days (78.4% vs. 66.7%) was comparable. The incidence of maternal cardiovascular
      side effects was lower in the atosiban group (4% vs. 78%, p=0.0). Tocolysis was
      terminated as a result of maternal adverse effects in the fenoterol group (9%).
      Fetal tachycardia was lower in the atosiban group (2% vs. 22%). The mean duration
      of tocolytic administration was lower in the atosiban group (19 h vs. 24.5 h,
      p<0.05). DISCUSSION: The adverse effects in the pulsatile administration of
      fenoterol for short duration were only dependent on the initial dosage for the
      arrest of preterm labour. Neonatal outcome were similar between the treatment
      groups and were rather related to the gestational age not to the tocolytic agent.
      CONCLUSIONS: Atosiban was comparable in clinical effectiveness and was associated
      with fewer maternal and fetal adverse effects, so that fenoterol cannot be
      recommended. Completion of tocolytic therapy 12 hours after arrest of preterm
      labour is effective and associated with a short mean duration.

PMID- 19856244
TI  - Massive labia minor hypertrophy following vulvar edema and abscess in pregnancy-
      case report.
AB  - A rare case is presented of vulvar edema and abscess with subsequent labia minor
      hypertrophy in a 26-year-old woman, which developed during two consecutive
      pregnancies with normal maternal and neonatal outcome. After a first pregnancy,
      the patient was initially treated conservatively, followed by incision of the
      abscess. After the second pregnancy, surgical correction of the hypertrophic
      labia minor was performed. The possible causes, complications and therapeutic
      options are discussed.

PMID- 19856245
TI  - [Smith-Lemli-Opitz syndrome--case report, diagnostics and therapeutic options].
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal-recessive disease characterised
      by the combination of (foetal) growth retardation, mental retardation and a
      typical malformation pattern. In particular, the combination of cardiovascular
      defects, Y-shaped syndactyly of the 2 (nd) and 3 (rd) toes and a distinctive
      craniofacial appearance, often including a cleft palate, are characteristic of
      SLOS. The disease is caused by a defect in cholesterol synthesis resulting in a
      reduced or absent activity of the enzyme 7-dehydrocholesterol reductase (DHCR7).
      As a consequence, a lack of cholesterol and an increase of toxic cholesterol
      precursors are observed in the majority of patients. We report on a female
      patient who was born at 37 weeks of gestation and was both small and light for
      gestational age who displayed typical signs of SLOS. After the diagnosis had been
      confirmed, a therapeutic approach with oral substitution of cholesterol and the
      administration of simvastatin was initiated. In spite of this strategy, the
      patient died at the age of 12 weeks from the disease. Based on the case
      presented, we review and discuss current diagnostic and therapeutic options for
      patients with SLOS.

PMID- 19856246
TI  - Process quality and incidence of acute complications in a series of more than
      230,000 outpatient colonoscopies.
AB  - BACKGROUND AND STUDY AIMS: Data on process quality and complications of
      colonoscopies are sparse, especially for the screening setting. We describe
      process quality in routine care, estimate the incidence of acute complications,
      and identify risk indicators for substandard care and complications. PATIENTS AND
      METHODS: We analyzed data from 236 087 compulsory health insurance (CHI) members
      who underwent colonoscopies in 2006. Data were documented prospectively in the
      Electronic Colonoscopy Documentation of the Bavarian Association of CHI
      Physicians, a registry of outpatient colonoscopies performed in practices
      throughout Bavaria, Germany. It covers demographic characteristics, indications,
      quality indicators, macroscopic and histological findings, diagnoses, and acute
      complications. RESULTS: Colon preparation resulted in clear bowels in 76.31 % of
      patients, liquid residues in 22.22 %, and dirty bowels in 1.47 %. In total, 92.85
      % of the examinations were performed with patients under sedation/analgesia and
      97.43 % of colonoscopies were complete. Photo documentation was present for 98.87
      %. Male sex, middle age, screening, satisfactory bowel preparation, and
      sedation/analgesia were associated with completeness. A total of 735 patients
      (0.31 %) suffered complications, among them 520 bleedings (0.22 %), 69
      perforations (0.03 %), and 152 cardiorespiratory complications (0.06 %). Male
      sex, higher age, nonscreening indication, biopsies, polypectomies, and absence of
      sedation/analgesia were indicative of a higher bleeding risk. Perforations were
      also related to biopsies and polypectomies. Higher age was the only discernible
      risk indicator for cardiorespiratory events. CONCLUSIONS: Outpatient colonoscopy
      is a safe procedure with a low risk of acute complications. Improving bowel
      preparation enhances completeness. Sedation/analgesia is conducive to both
      completeness and the lowering of the risk of acute complications.

PMID- 19856247
TI  - Reflux and Barrett's disease.

PMID- 19856248
TI  - Colonoscopy, tumors, and inflammatory bowel disease.

PMID- 19856249
TI  - A simple single serum method to measure fractional calcium absorption using dual
      stable isotopes.
AB  - The dual stable isotope method with a timed 24-h urine collection is the gold
      standard approach to measure fractional calcium absorption. However, the need to
      collect urine for 24 h makes this technique time-consuming and laborious. Our
      study sought to determine whether a dual isotope method using a single serum
      sample obtained 4 h after administration of the initial isotope provides a useful
      approach to measure fractional calcium absorption. Following a metabolic diet
      with a fixed calcium intake of 30 mmol/day for 10 days, nineteen healthy subjects
      age 54-74 were given a test meal with an oral isotope ((44)Ca) followed 2 h later
      by an intravenous isotope ((42)Ca). Once the oral isotope was administered, urine
      was collected for 24 h, and a serum sample was obtained after 4 h. The ratio of
      the oral to intravenous isotopes was measured in the urine and serum by mass
      spectroscopy. Fractional calcium absorption was 16.2 +/- 7.7% by the 4-h single
      serum method versus 18.5 +/- 7.5% by the 24-h urine method. There was a small
      mean difference between the urine and serum methods of 2.33% with a confidence
      interval -3.97 to 8.60%. The two methods showed a strong linear association (r =
      0.912, p<0.001). Use of dual stable isotopes with a 4-h single serum method gives
      fractional calcium absorption values that are 12.5% lower than with the 24-h
      urine method; however, it rank orders subjects accurately thus making it a useful
      alternative method in clinical research applications.

PMID- 19856250
TI  - Obesity: a complex growing challenge.
AB  - The prevalence of overweight and obesity is increasing worldwide. The
      physiological mechanisms involved in body weight regulation are complex and
      incompletely understood. Increasing evidence suggests that obesity is a
      multifactorial disease where many, if not all, organs of the body are involved.
      The adipose tissue was considered as a simple fat accumulation for a long period
      of time. However, nowadays it is fascinating to progressively discover its
      involvement in hormonal, inflammatory or immune system dysregulation. Adipokines
      and cytokines are involved in control and regulation of appetite and energy
      balance, glucose and lipid metabolism, neuroendocrine function, reproduction,
      immunity, and cardiovascular function. The inflammatory background associated
      with obesity is closely related to insulin resistance. Moreover, the inhibitory
      effect of endocannabinoids on the expression of adiponectin could be involved in
      insulin resistance. Gut microbiota related factor may be responsible for the
      development of diet-induced obesity and diabetes through metabolic endotoxemia
      which triggers the inflammatory tone. Based on recent research, several
      physiopathological mechanisms involved in the development of obesity are
      reviewed.

PMID- 19856251
TI  - Blockade of the RAS increases plasma adiponectin in subjects with metabolic
      syndrome and enhances differentiation and adiponectin expression of human
      preadipocytes.
AB  - AIMS: This observational study aimed to investigate the effects of renin
      angiotensin system (RAS) blockers on plasma adiponectin in subjects with
      metabolic syndrome (Mets) and differentiation, adiponectin expression of human
      omental (OM) and subcutaneous (SC) preadipocytes. METHODS: Fifty-three patients
      with Mets were treated with angiotensin converting enzyme inhibition (ACEI),
      angiotensin II receptor blocker (ARB) or nothing, lipid profile and adiponetin
      were measured. OM and SC preadipocytes were obtained from sixteen normal non
      menopausal women undergoing elective abdominal surgery and subsequently
      differentiated in the presence of ACE, ARB or thiazolidinedione (TZD).
      Differentiation was assessed using a number of biochemical and function
      parameters. RESULTS: Plasma adiponectin was increased dramatically as a result of
      ACEI and ARB treatment. Most of the metabolic and differentiating parameters were
      improved significantly by RAS blockers or TZD. Compared with TZD, RAS blockers
      have stronger effects on omental preadipocytes in differentiation and insulin
      sensitivity. The improvement of adiponectin mRNA expression was significantly
      greater in ARB-treated omental preadipocytes compared with TZD-treated ones.
      CONCLUSION: These results suggest that adiponectin may serve as potential
      therapeutic targets of ACEI and ARB for treating the Mets and its related
      complications. It also suggests a potential benefit of RAS blockers on Mets with
      characteristic visceral obesity.

PMID- 19856252
TI  - A novel mutation (V101A) of the LHX4 gene in a Japanese patient with combined
      pituitary hormone deficiency.
AB  - OBJECTIVE: LHX4, a LIM-homeodomain transcription factor, is required for
      development of the pituitary and nervous system. Several mutations of the LHX4
      gene have been identified in patients with combined pituitary hormone deficiency
      (CPHD). The objective of the study was to clarify the molecular basis of a
      Japanese patient of CPHD with a small anterior pituitary and an ectopic posterior
      pituitary. METHODS: Genomic DNA was extracted from blood samples of the patient.
      Exons and exon-intron junctions of the LHX4 gene were amplified and sequenced. An
      expression vector of the mutant LHX4 protein was constructed and its function was
      analyzed in vitro. RESULTS: A novel missense mutation (V101A) was identified. IN
      VITRO transfection studies demonstrated that V101A mutant LHX4 was unable to
      activate the POU1F1 and FSHbeta subunit gene promoter, indicating a loss of
      function mutation. CONCLUSION: Our results identify a novel loss of function
      mutation of the LHX4 gene in a Japanese patient with CPHD.

PMID- 19856253
TI  - Mutational characterization of steroid 21-hydroxylase gene in Portuguese patients
      with congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is
      a common inherited disorder of adrenal hormone biosynthesis due to mutations in
      the 21-hydroxylase gene, CYP21A2. Genotyping for ten of the most frequent
      mutations was performed in 84 Portuguese CAH patients: 10 salt-wasters, 6 simple
      virilizers and 68 non-classical patients. The patients were diagnosed by a level
      of 17-hydroxyprogesterone above 10 ng/ml either in basal conditions or after an
      ACTH 0,25 mg IV Test. A variety of genotyping techniques were used to detect
      these ten mutations. CYP21A2 mutations were detected in 91.7% (77/84) of the
      patients. The frequency of alleles carrying two or more CYP21A2 mutations (9.5% -
      16/168) is higher than in other populations. The most frequent mutations
      identified in our population were V281L (41.7%) and deletions/conversions
      involving the promoter region of the CYP21A2 gene (28.3%). A decreased frequency
      of IVS2-12C/A>G mutation (5.6%) was the most characteristic feature of our
      population. This study allow the characterization of the mutational spectrum of
      CAH patients, mainly non-classical CAH, with 21-hydroxylase deficiency from
      Portugal showing specific genetic features of this population which reveals
      differences with worldwide countries.

PMID- 19856254
TI  - Insulin alters the permeability of sheep pleura.
AB  - AIM: Insulin promotes ion transportation across epithelia, mainly kidneys,
      leading to water and electrolyte abnormalities, possibly causing 'insulin oedema
      syndrome', which rarely presents as pleural effusion. Direct stimulation of sheep
      pleura by insulin and the possible electrophysiology mechanisms involved were
      investigated. MATERIAL AND METHODS: Sheep visceral and parietal pleural specimens
      were mounted between Ussing chambers. Insulin solutions (10 (-9) to 10 (-5) M), L
      NAME, Nitroprussid sodium, amiloride and ouabain were used. Trans-mesothelial
      Resistance was determined. Immunohistochemistry for presence of Insulin Receptors
      was performed. RESULTS: Insulin increased Trans-mesothelial Resistance within 1st
      minute when added mesothelially of visceral (p=0.008) and parietal pleura
      (p=0.046) for concentrations higher than 10 (-7) M. L-NAME or Nitroprussid sodium
      didn't but amiloride and ouabain inhibited insulin's effect. Immunohistochemistry
      revealed the presence of Insulin Receptors. CONCLUSION: Insulin changes the
      permeability of sheep pleura by altering its electrophysiology and may interfere
      in pleural effusion formation. Involvement of Insulin Receptors may be suggested.

PMID- 19856255
TI  - A novel GNAS1 mutation in a German family with Albright's hereditary
      osteodystrophy.
AB  - Albright's hereditary osteodystrophy (AHO) is an inherited disorder and results
      from heterozygous loss of function mutation within the human G (s)alpha gene
      (GNAS1). AHO appears in two phenotypes, that may occur within the same family.
      Pseudohypoparathyroidism type Ia (PHP Ia) comprises the clinical features of AHO
      associated with parathyroid hormone (PTH) resistance while pseudo
      pseudohypoparathyroidism (PPHP) includes AHO features without PTH resistance. In
      the present study we report a mother and a daughter with PPHP and PHP Ia
      respectively. The 13 exons of GNAS1 were analysed by PCR and direct sequencing.
      We identified a heterozygous missense mutation in exon 1. This novel mutation
      results in a stop at codon 35 and a truncated non-functional GNAS1 protein.

PMID- 19856256
TI  - Real-time elastography and contrast-enhanced ultrasound for the assessment of
      thyroid nodules.
AB  - OBJECTIVE: Work-up of thyroid nodules remains challenging. Recent technologies
      enable determination of tissue elasticity and perfusion using ultrasound devices.
      The aim of the present study was to evaluate real-time elastography (RTE) and
      contrast-enhanced ultrasound with Sonovue (CEUS) for the differentiation of
      benign and malignant thyroid nodules. MATERIALS AND METHODS: Inclusion criteria
      were: nodules >=1 cm, non-functioning or hypo-functioning on radionuclide
      scanning, and cytological/histological assessment. All patients received
      conventional ultrasound, RTE and CEUS. RTE was classified as: Elasticity-Score
      (ES)1 = soft, ES2 = predominantly soft, ES3 = predominantly hard, ES4 = hard
      nodule. CEUS-video clips were digitally recorded and analyzed using time
      intensity-curves within selected regions-of-interest. RESULTS: Fifty-three
      nodules in 50 patients were available for analysis. Forty-six nodules were benign
      on cytology/histology, 6 nodules were papillary carcinoma and one nodule was a
      follicular carcinoma. Nodule margin irregularity was the ultrasound pattern most
      predictive of malignancy with sensitivity 57% (95% confidence interval: 18-90%)
      and specificity 85% (71-94% p<0.05). When using ES3&4 for the diagnosis of
      malignant nodules sensitivity and specificity were 86% (42-99.7%) and 87% (75
      95%), respectively (p = 0.0003). The only malignant nodule missed with RTE was a
      follicular carcinoma. Sensitivity for the diagnosis of papillary carcinoma
      therefore was 100%. No specific CEUS pattern could be identified to differentiate
      between benign and malignant nodules. CONCLUSIONS: RTE seems to be a useful tool
      in the work-up of thyroid nodules to exclude papillary thyroid cancer. However,
      follicular carcinoma remains a challenging problem. CEUS did not improve the
      characterization of thyroid nodules in this preliminary study.

PMID- 19856257
TI  - Thyroid remnant dose: 124I-PET/CT dosimetric comparison of rhTSH versus thyroid
      hormone withholding before radioiodine remnant ablation in differentiated thyroid
      cancer.
AB  - AIM: Recombinant human thyroid-stimulating hormone (rhTSH) recently was approved
      as an alternative to thyroid hormone withholding (THW) to elevate TSH for thyroid
      remnant ablation in differentiated thyroid carcinoma patients. High ablation
      success rates are reported with diverse rhTSH-aided (131)I activities. Improved
      renal function causes approximately 50% faster radioiodine clearance under
      euthyroidism versus hypothyroidism. Knowledge of comparative remnant radioiodine
      kinetics, particularly the remnant radiation dose in Gy/GBq of administered
      (131)I activity (RDpA), could assist in choosing rhTSH-aided ablative activities.
      MATERIAL AND METHODS: To compare the RDpA, determined through (124)I-positron
      emission tomography/computed tomography (PET/CT), under the two stimulation
      methods, we retrospectively divided into two groups 55 consecutive totally
      thyroidectomized, radioiodine-naive patients. The rhTSH group (n=16) received
      (124)I on thyroid hormone, 24 h after two consecutive daily intramuscular
      injections of rhTSH, 0.9 mg. The THW group (n=39) received (124)I after weeks
      long THW, when serum TSH first measured > or = 25 mIU/L. We performed PET
      investigations 4 h, 24 h, 48 h, 72 h and 96 h and PET/CT 25 h after (124)I
      administration. RESULTS: Median stimulated serum thyroglobulin was 15 times
      higher (p=0.023) and M1 disease almost twice as prevalent (p=0.05) in rhTSH
      versus THW patients. Mean+/-standard deviation RDpA was statistically equivalent
      between the groups: rhTSH, 461+/-600 Gy/GBq, THW, 302+/-329 Gy/GBq, two-sided
      p=0.258. CONCLUSIONS: rhTSH or THW deliver statistically equivalent radiation
      doses to thyroid remnant and may be chosen based on safety, quality-of-life,
      convenience and pharmacoeconomic factors. Institutional fixed radioiodine
      activities formulated for use with THW need not be adjusted for rhTSH-aided
      ablation.

PMID- 19856259
TI  - Long term follow-up of patients with adrenal incidentalomas--a single center
      experience and review of the literature.
AB  - INTRODUCTION: Adrenal incidentalomas (AIs) constitute an emerging clinical entity
      due to the increased use of abdominal imaging for diagnostic purposes. Most often
      it consists of benign-nonfunctioning lesions and an increase in size during
      follow-up is reported in about 9% (0-26%), whereas their functional evolution is
      rare. MATERIALS AND METHODS: Sixty-four patients (22 males and 42 females; mean
      age 61.6 +/- 1.2 years), with AIs and follow-up of 3.1 +/- 0.4 years (range 0-19)
      were retrospectively evaluated. The patients underwent basal and dynamic
      evaluation of the hypothalamic-pituitary-adrenal axis, renin-angiotensin
      aldosterone system and adrenomedullary function. Mass enlargement and adrenal
      hyperfunction were estimated at yearly intervals. RESULTS: Adrenalectomy was
      performed in 5 patients (4 benign cortical adenomas and 1 pheochromocytoma).
      Abnormal manifestation, based on clinical, laboratory and histological
      evaluation, was observed in 4 patients [1 (1.56%) with SCS, 2 (3.12%) with
      pheochromocytoma and 1 (1.56%) with aldosteronoma], 3 of which were diagnosed at
      their initial evaluation and 1 at the 3 (rd) year of follow-up. The remainders
      [60 patients (93.75%)] were harbouring a non-secretory mass (8 potential
      myelolipomas, 8 nodular hyperplasias, 3 cystic lesions). Eleven patients (17.2%)
      had bilateral AIs. Mass enlargement (5-13 mm) was observed in 9 patients (14%),
      >=10 mm 4 (6.25%), while mass shrinkage (5-19 mm) in 3 (4.7%) during follow-up.
      No hormonal evolution was noticed. CONCLUSIONS: AIs present usually as benign,
      non-secretory lesions. Criteria for surgical intervention were met at initial
      assessment for the majority of AIs. Size alterations during follow-up are
      uncommon and functional evolution is rare.

PMID- 19856258
TI  - The use of thyrogen in the treatment of differentiated thyroid carcinoma: an
      intraindividual comparison of clinical effects and implications of daily life.
AB  - AIM: Withdrawal of levothyroxine with resultant hypothyroidism is still used in
      preparation for I-131 diagnostic whole-body scan (DWBS) and thyroglobulin (TG)
      measurement in patients afflicted with differentiated thyroid cancer (DTC).
      Recombinant human thyroid-stimulating hormone (rhTSH) enhances TSH stimulation
      obviating the clinical and economical consequences of hypothyroidism. Primary aim
      of this study was an intraindividual comparison of diagnostic follow-up
      measurements under these two sets of conditions by taking clinical and socio
      economic parameters into account. Second aim was to determine a clear patient
      preference for the one method or the other. METHODS: This non-interventional
      observational study included patients (n=192 signed informed consent, n=128
      protocol compliant patients without need for therapeutic intervention) with DTC
      first treated by thyroidectomy and radioiodine ablation. Control visits including
      I-131 DWBS were planned at 3-6 months post-thyroidectomy after a phase (KU 1) of
      thyroid hormone withdrawal (THW) and again after 6-12 months later in a euthyroid
      state under exogenous stimulation with rhTSH (KU 2). Study design was open,
      prospective and multicentric. Data collected consisted of patient information (SF
      12 ((r)) Health Survey), thyroid-specific results of clinical examinations and
      several aspects of daily life, e. g., employment, days of absence from work and
      other economic aspects. RESULTS: In contrast to KU 1, in KU 2 there is a highly
      significant improvement (p<0.0001) in all studied clinical symptoms and aspects
      of managing daily life. A significant increase of the SF-12 ((r)) health survey
      score could also be identified. Mental score showed a higher increase than
      physical score. Included patients were less absent from work before KU 2, (absent
      4.5%, median 4 days in euthyroid state [range 2-5 d]), vs. before KU 1 (absent
      47.8%, median 10 days in hypothyroid state [range 1-30 d]). After KU 2 7.7% of
      the euthyroid patients was absent from work (median 5 days) while 37.5% was after
      KU 1 (median 6 days). CONCLUSION: Included patients benefited subjectively and
      objectively from the use of rhTSH for diagnostic procedures in the treatment of
      DTC. A clear preference (127 of 128) of analyzed patients could be identified for
      exogenous stimulation with rhTSH.

PMID- 19856260
TI  - Chronic acetonemia alters liver oxidative balance and lipid content in rats. A
      model of NASH?
AB  - Acetone is considered to be a substance that can disturb cellular oxidative
      status, being also associated with the production of glucose during its
      metabolization. The objective of the present study was to determine the effects
      of chronic treatment with acetone in oxidative stress and metabolic parameters in
      rats. Twenty male Wistar rats were divided into two groups: control (CG) and
      chronic acetone group (CAG). After 28 days of acetone ingestion in a 5% aqueous
      solution (CAG) or water (CG) the animals were euthanized and urine, plasma and
      liver were collected for the determination of acetone, glucose, lipemia, hepatic
      fat, malondialdehyde (MDA), reduced glutathione (GSH), and vitamin E. As
      expected, urinary and plasma acetone levels were higher in CAG. There was no
      difference in hepatic MDA values between groups, whereas hepatic GSH was lower in
      CAG than in CG and hepatic vitamin E was higher in CAG than in CG. There was also
      an increase in glycemia, cholesterolemia and hepatic fat in CAG compared to CG.
      Chronic treatment with a 5% acetone solution produced an increase in acetonemia
      that was able to promote changes in hepatic oxidative metabolism and in lipid
      content in rats similar to those observed in nonalcoholic steatohepatitis.

PMID- 19856261
TI  - N-terminal pro-brain natriuretic Peptide as a biomarker for hypertensive
      disorders of pregnancy.
AB  - We tested the hypothesis that the cardiac biomarker N-terminal pro-brain
      natriuretic peptide would be elevated in hypertensive disorders of pregnancy,
      with an increase in levels of this biomarker across increasing gradations of
      disease severity. We performed a case-controlled study of women admitted to labor
      and delivery at the Hospital of the University of Pennsylvania between 24 and 42
      weeks of gestation. Cases had hypertension that developed after 20 weeks of
      gestation, and controls were normotensive women presenting for delivery. N
      terminal pro-brain natriuretic peptide levels were compared between cases ( N =
      83) and controls ( N = 290). Cases were subclassified into gestational
      hypertension ( N = 20) and mild ( N = 15) and severe preeclampsia ( N = 48), and
      N-terminal pro-brain natriuretic peptide levels were compared between these
      subgroups. N-terminal pro-brain natriuretic peptide levels were higher in cases
      than in controls (81 pg/mL versus 37 pg/mL, P < 0.001), with a graded increase in
      levels from gestational hypertension (64 pg/mL) to preeclampsia (89 pg/mL) to
      severe preeclampsia (157 pg/mL; P < 0.001). Each log increase in N-terminal pro
      brain natriuretic peptide doubled the risk of preeclampsia (odds ratio = 2.10 P <
      0.001). N-terminal pro-brain natriuretic peptide levels were increased in
      hypertensive disorders of pregnancy and discriminate between subcategories of
      disease.

PMID- 19856262
TI  - Comparison of electromyographic recordings during labor in women with an anterior
      or posterior placenta.
AB  - We sought to determine whether placental implantation site affects
      electromyographic (EMG) recordings of uterine activity in labor. We performed a
      prospective study of women randomly selected on admission to labor ward. There
      were acceptable recordings in 36 women, 18 in both the posterior and anterior
      placenta groups. There were 12 unacceptable recordings. This was mainly due to
      poor electrode contact. There was no difference in amplitude, frequency, activity
      integral, total activity integral, or power density in either group. EMG can be
      used to quantify uterine activity irrespective of placental position.

PMID- 19856263
TI  - Perinatal outcomes in isolated single umbilical artery.
AB  - We sought to determine the rate of adverse perinatal outcomes in pregnancies
      diagnosed with an isolated single umbilical artery (SUA). We performed a
      retrospective review comparing 68 pregnancies with an isolated SUA to 68
      pregnancies with a three-vessel cord (3VC). Pregnancies with structural or
      karyotypic anomalies were excluded. Gestational age at delivery, birth weight,
      SGA rate, ponderal index, and rates of admission to the neonatal intensive care
      unit were compared between groups. Student T test and chi-square analysis were
      performed. Neonates with isolated SUA had a significantly smaller birth weight
      than those with a 3VC (3279 +/- 404 g versus 3423 +/- 374 g, P = 0.0168). There
      was no significant difference in rates of SGA (17.6% versus 8.8%, P = 0.06).
      Ponderal index was significantly less in those with SUA compared with 3VC (24.2
      +/- 1.1 g/cm(3) versus 26.1 +/- 1.3 g/cm(3), P = 0.001). SUA neonates had a
      significantly longer length of neonatal intensive care unit stay than 3VC
      neonates (1.25 +/- 2.2 days versus 0.48 +/- 1.25 days, P < 0.023). Fetuses with a
      prenatal diagnosis of isolated umbilical artery have a significantly lower
      ponderal index compared with fetuses with a 3VC. Pregnancies with isolated SUA
      should undergo serial assessments for fetal growth.

PMID- 19856264
TI  - Correlating cell architecture with osteogenesis: first steps towards live single
      cell monitoring.
AB  - Cell shape and regulation of biological processes such as proliferation and
      differentiation are to a large degree connected. Investigation of the possible
      relationship between cell shape and function is therefore important for
      developing new material concepts for medical applications as well as developing
      novel cell based sensors. Cell spreading requires a firm contact with the
      underlying substrate, with focal contacts (FC) being the primary sites of
      adhesion. They consist of a large number of clustered transmembrane proteins
      (integrins). FC integrins connect the cell cytoskeleton with the cell substratum.
      It has been demonstrated that cell spreading increases osteoblast differentiation
      in pre-osteoblastic progenitors. The gradual process of osteogenesis can be
      followed by different proteins being expressed at various time points, comprising
      early (e.g., bone-specific alkaline phosphatase (bALP)) and late genes (e.g.,
      osteocalcin (OC)). In the present study we have used immunohistochemistry and RT
      PCR to determine osteogenic differentiation of human bone cells (HBC). For online
      monitoring, fluorescently-tagged actin and vinculin were used for transfection of
      HBCs. Transfection of HBCs with an OC promoter gene construct allowed us to
      online monitor the gradual process of osteogenesis. We found distinct changes in
      cell architecture upon osteogenic differentiation thus providing evidence for the
      connection between cell shape and functional state.

PMID- 19856266
TI  - Phagocytosis of staphylococci biofilms by polymorphonuclear neutrophils: S.
      aureus and S. epidermidis differ with regard to their susceptibility towards the
      host defense.
AB  - Bacteria organized in biofilms are a common cause of relapsing or persistent
      infections. In patients receiving orthopedic implants, such as endoprostheses or
      osteosynthesis materials, Staphylococcus aureus and S. epidermidis are prevalent
      and it is widely assumed that bacteria in biofilms are not only relatively
      resistant towards antibiotics and biocides, but also towards host defense
      mechanisms. In that context, we addressed the question how polymorphonuclear
      neutrophils (PMN), the "first line defense" against bacterial infection, interact
      with biofilms generated in vitro. By time-lapse video microscopy, we observed
      migration of PMN towards the biofilms. In the case of S. aureus, the PMN moved
      across the biofilm and took up bacteria as they moved along. On S. epidermidis,
      in contrast, the PMN were rather immobile, and phagocytosis was limited to
      bacteria in the immediate vicinity. By labeling the bacteria within the biofilm
      with H-thymidine we found that S. aureus biofilms were more sensitive towards the
      PMN attack than S. epidermidis. Following phagocytosis of either bacteria strain,
      the PMN underwent apoptosis, in line with the dogma, that phagocytosis induces
      programmed cell-death in order to prevent spilling of the bactericidal and
      cytotoxic entities. In conclusion, biofilms are not inherently protected against
      the attack by phagocytic cells; their sensitivity, however, varies among
      bacterial strains, presumably due to properties of the extracellular biofilm
      matrix affecting the motility of PMN on the film.

PMID- 19856267
TI  - The photodynamic effect of tetra-substituted N-methyl-pyridyl-porphine combined
      with the action of vancomycin or host defense mechanisms disrupts Staphylococcus
      epidermidis biofilms.
AB  - The skin commensal and opportunistic pathogen Staphylococcus epidermidis is an
      important cause of nosocomial infections. Virulence is attributable to formation
      of biofilm, which provides a microenvironment that protects the bacterium from
      attack by the host immune system and by chemotherapy. In this study we extended
      to S. epidermidis strategies previously aimed at treatment of S. aureus biofilms
      using photodynamic treatment (PDT) combined with chemotherapy or phagocytosis. A
      significant reduction in bacterial survival was observed when structurally
      distinct biofilms were exposed to the cationic porphyrin, tetra-substituted N
      methyl-pyridyl-porphine (TMP), and simultaneously to visible light. Of note, the
      extent of biofilm clearance depended on its maturation stage: developing, young
      biofilms, were more sensitive towards PDT than mature biofilms. Furthermore, PDT
      treated biofilms exposed to vancomycin or subjected to phagocytic action of whole
      blood were almost completely eradicated. The data we obtained establish that PDT
      combined with antibiotics or host defenses may also be a useful approach for the
      inactivation of S. epidermidis biofilms.

PMID- 19856268
TI  - New concepts and new weapons in implant infections.
AB  - Molecular studies have cast light on new facts about the virulence factors of
      bacteria responsible for implant infections. Recently, the biofilm matrix has
      been shown to include a variety of important structural components, including
      DNA, in addition to polysaccharides and proteins. This finding has stimulated
      interest in substances able to disrupt biofilms by attacking both the poly-N
      acetylglucosamine surface polysaccharide (PNAG) and the extracellular DNA (eDNA),
      namely, dispersin B, a PNAG-degrading enzyme, and DNase I. The therapeutic
      potential of these enzymes are reviewed in this issue of IJAO, as well as the
      ability of the excretions/secretions of the medicinal maggot Lucilia sericata to
      disrupt Staphylococcus epidermidis biofilms. The activity of bacterial proteases
      causes the release of eDNA, critical for the early development of biofilms. This
      complex process, including suicidal and fratricidal mechanisms, is also presented
      in the current issue of IJAO. The different sensitivities of S. aureus and S.
      epidermidis to enzymatic anti-biofilm agents and to the host's first line of
      defense, as well as the importance of knowing the cascade of regulatory genes in
      bacteria so as to interfere with biofilm production using gene therapy or quorum
      sensing inhibitors are also discussed in this issue. Other innovative approaches
      consist in disrupting biofilms by exposing them to photodynamic substances and
      simultaneously to visible light, and in coating biomaterial surfaces with organic
      molecules to prevent protein adsorption and biofilm formation.

PMID- 19856269
TI  - OpuC--an ABC transporter that is associated with Staphylococcus aureus
      pathogenesis.
AB  - RIP is a novel antibiotic against staphylococci. It acts at least in part by
      competing with RNAIII activating protein (RAP) by downregulating TRAP histidine
      phosphorylation, and by downregulating the expression of the acessory gene
      regulator (agr). While much is known about the function of the agr as a quorum
      sensing system that regulates virulence, not much is known about TRAP. TRAP is a
      167-kDa protein that is highly conserved among staphylococci and is involved in
      DNA protection from stress. TRAP is membrane-associated but does not have a
      transmembrane domain, and thus it may be bound to the membrane through other
      proteins. To search for these proteins, protein-protein interaction studies were
      carried out using a bacterial two-hybrid system, and OpuCA was discovered as a
      TRAP-binding protein. OpuCA is an ATP binding-cytoplasmic (ABC) domain of an OpuC
      ABC transporter. S. aureus OpuC- mutant strain was constructed and shown to be
      less tolerant to salt stress, and was defective in choline uptake. OpuC- cells
      were less pathogenic and showed reduced TRAP phosphorylation and agr activity,
      did not respond to RAP, and were defective in biofilm formation in vitro and in
      vivo. These results suggest that OpuC acts as a transporter and also plays a role
      in S. aureus pathogenesis.

PMID- 19856270
TI  - Regulation of biofilm formation by sigma B is a common mechanism in
      Staphylococcus epidermidis and is not mediated by transcriptional regulation of
      sarA.
AB  - Biofilm formation is a major pathogenetic factor of Staphylococcus epidermidis.
      In S. epidermidis the alternative sigma factor sigma B was identified to regulate
      biofilm formation in S. epidermidis 1457. In S. aureus sigma B dependent
      regulation plays a minor role, whereas sarA (Staphylococcus accessory regulator)
      is an essential regulator. Therefore, we investigated the impact of sigma B on
      sarA transcription and biofilm formation in three independent S. epidermidis
      isolates. Mutants with dysfunctional sigma B displayed a strongly reduced biofilm
      formation, whereas in mutants with constitutive sigma B activity biofilm
      formation was increased. Transcriptional analysis revealed that icaA
      transcription was down-regulated in all sigma B negative mutants while icaR
      transcription was up-regulated. However, transcriptional differences varied
      between individual strains, indicating that additional sigma B-dependent
      regulators are involved in biofilm expression. Interestingly, despite the
      presence of a sigma B promoter beside two sigma A promoters no differences, or
      only minor ones, were observed in sarA transcription, indicating that sigma B
      dependent sarA transcript has no influence on the phenotypic changes. The data
      observed in independent clinical S. epidermidis isolates suggests that, in
      contrast to S. aureus, regulation of biofilm formation by sigma B is a general
      feature in S. epidermidis. Additionally, we were able to demonstrate that the
      sarA- dependent regulation is not involved in this regulatory pathway.

PMID- 19856271
TI  - TRAP plays a role in stress response in Staphylococcus aureus.
AB  - Staphylococci are common pathogens of implant-related infections. RIP is a
      heptapeptide (YSPWTNF-NH2 ) that was shown to be very effective in preventing and
      treating antibiotic-resistant staphylococcal infections, in healing polymicrobial
      wounds, and in enhancing the effect of commonly used antibiotics. How the peptide
      negatively affects the survival of the bacteria in the host is not yet known. In
      staphylococci, RIP was shown to suppress toxin production by inhibiting the
      expression of agr and production of RNAIII. RIP was also shown to suppress the
      phosphorylation of TRAP (target of RNAIII-activating peptide), whose function was
      not clear. Here we show that mutant S. aureus TRAP- cells were more sensitive to
      oxidative stress and had higher rates of spontaneous and adaptive (agr)
      mutations. Furthermore, recombinant TRAP protected DNA from oxidative damage
      caused by hydroxyl radicals. Put together, these results suggest that TRAP is
      involved in DNA protection from stress. RIP may thus suppress pathogenesis
      through multiple independent molecular mechanisms involving both suppression of
      virulence and suppression of stress response.

PMID- 19856272
TI  - Description of a new group of variants of the Staphylococcus aureus elastin
      binding protein that lacks an entire DNA segment of 180 bp.
AB  - The elastin-binding protein (EbpS) is a microbial surface component recognizing
      adhesive matrix molecule (MSCRAMM) found in Staphylococcus aureus that mediates
      bacterial cell binding to soluble elastin and tropoelastin. In scientific
      literature it is well established that the gene encoding for the elastin-binding
      protein (ebpS) is present in the vast majority of Staphylococcus aureus clinical
      isolates. The present study aimed at investigating a group of new variant forms
      of ebpS gene identified in S. aureus clinical strains isolated from implant
      related orthopedic infections. A PCR screening for the ebpS gene, conducted on
      over two hundred S. aureus clinical isolates from implant-related infections
      revealed the detection of six strains exhibiting an altered amplicon size,
      shorter than expected. In order to elucidate the sequence changes present in
      these gene variants, the trait comprised between the primers was analyzed in all
      six isolates bearing the modification and in four isolates exhibiting the regular
      amplicon size. A similar form of the ebpS gene, lacking a DNA trait of 180 bp,
      was confirmed in all six isolates independently of their clonal origin.
      Interestingly, only three of these isolates, all with type IV polymorphism of the
      accessory genes regulator (agr) locus, showed exactly the same sequence and,
      thus, the same pattern of point mutations with respect to reference strains. From
      nucleotide translation, the corresponding encoded protein was found to lack an
      entire peptide segment of 60 amino acids. From nucleotide sequence translation,
      this modification was found to implicate the disappearance of an entire
      hydrophobic domain, whose functional significance needs to be further
      investigated.

PMID- 19856273
TI  - Surface protein EF3314 contributes to virulence properties of Enterococcus
      faecalis.
AB  - PURPOSE: Identification of putative new virulence factors as additional targets
      for therapeutic approaches alternative to antibiotic treatment of multi-resistant
      enterococcal infections. METHODS: The EF3314 gene, coding for a putative surface
      exposed antigen, was identified by the analysis of the Enterococcus faecalis V583
      genome for LPXTG-motif cell wall anchor surface protein genes. A non-polar EF3314
      gene deletion mutant in the E. faecalis 12030 human clinical isolate was
      obtained. The wild type and the isogenic mutant strain were investigated for
      biofilm formation, adherence to Hela cells, survival in human macrophages and a
      Caenorhabditis elegans infection model. The aminoterminal portion of the EF3314
      protein was overexpressed in E. coli to obtain mouse polyclonal antibodies for
      use in Western blotting and immunolocalization experiments. RESULTS: The EF3314
      gene has an unusually high GC content (46.88% vs. an average of 37.5% in the E.
      faecalis chromosome) and encodes a protein of 1744 amino acids that presents a
      series of 14 imperfect repeats of 90 amino acids covering almost the entire
      length of the protein. Its global organization is similar to the alpha-like
      protein family of group B streptococci, enterococcal surface protein Esp and
      biofilm associated protein Bap from S. aureus. The EF3314 gene was always present
      and specific for E. faecalis strains of human, food and animal origin.
      Differences in size depended on variable numbers of repeats in the repetitive
      region. CONCLUSIONS: EF3314 is a newly described, surface exposed protein that
      contributes to the virulence properties of E. faecalis.

PMID- 19856274
TI  - Disruption of Staphylococcus epidermidis biofilms by medicinal maggot Lucilia
      sericata excretions/secretions.
AB  - Chronic infections are commonly associated with biofilms formed by bacteria such
      as Staphylococcus epidermidis. With the increase in antibiotic resistant
      bacteria, maggot debridement therapy has been reintroduced for the treatment of
      chronic wounds. Studies have shown that the excretion/ secretions (ES) of Lucilia
      sericata larvae (maggots) contain many bioactive compounds which may contribute
      to the efficacy of maggot therapy. The present study evaluates the effect of L.
      sericata ES on the formation and disruption of S. epidermidis 1457 and 5179-R1
      biofilms. These strains employ either polysaccharide intercellular adhesin (PIA)
      or accumulation associated protein (Aap) for intercellular adhesion. A
      semiquantitative biofilm assay was used to measure the formation/disruption of S.
      epidermidis 1457 and 5179-R1 biofilms by ES. ES activity was characterized
      according to concentration, incubation time and temperature, thermal stability,
      and size. Immunofluorescence microscopy was used to ascertain the effect of ES on
      PIA and Aap. In the presence of ES, S. epidermidis 1457 and 5179-R1 nascent
      biofilm formation was inhibited, and pre-formed biofilms disrupted. ES activity
      was temperature and time dependent, inactivated by heat treatment, and disruption
      depended on the mechanism of intercellular adhesion. The molecule(s) responsible
      was >10 kDa in size and appeared to have protease or glucosaminidase activity. ES
      interferes with S. epidermidis biofilm formation, specifically degrading factors
      employed in biofilm accumulation, which would increase bacterial susceptibility
      to antibiotics and the host's immune system. In purified form, ES-factors may
      have general applicability for the treatment or prevention of chronic biofilm
      infections caused by staphylococci.

PMID- 19856275
TI  - Classification of array CGH data using smoothed logistic regression model.
AB  - Array comparative genomic hybridization (aCGH) provides a genome-wide information
      of DNA copy number that is potentially useful for disease classification. One
      immediate problem is that the data contain many features (probes) but only a few
      samples. Existing approaches to overcome this problem include features selection,
      ridge regression and partial least squares. However, these methods typically
      ignore the spatial characteristic of aCGH data. To explicitly make use of this
      spatial information we develop a procedure called smoothed logistic regression
      (SLR) model. The procedure is based on a mixed logistic regression model, where
      the random component is a mixture distribution that controls smoothness and
      sparseness. Conceptually such a procedure is straightforward, but its
      implementation is complicated due to computational problems. We develop a fast
      and reliable iterative weighted least-squares algorithm based on the singular
      value decomposition. Simulated data and two real data sets are used to illustrate
      the procedure. For real data sets, error rates are calculated using the leave-one
      out cross validation procedure. For both simulated and real data examples, SLR
      achieves better misclassification error rates compared with previous methods.

PMID- 19856276
TI  - A bivariate survival model with compound Poisson frailty.
AB  - A correlated frailty model is suggested for analysis of bivariate time-to-event
      data. The model is an extension of the correlated power variance function (PVF)
      frailty model (correlated three-parameter frailty model) (J. Epidemiol. Biostat.
      1999; 4:53-60). It is based on a bivariate extension of the compound Poisson
      frailty model in univariate survival analysis (Ann. Appl. Probab. 1992; 4:951
      972). It allows for a non-susceptible fraction (of zero frailty) in the
      population, overcoming the common assumption in survival analysis that all
      individuals are susceptible to the event under study. The model contains the
      correlated gamma frailty model and the correlated inverse Gaussian frailty model
      as special cases. A maximum likelihood estimation procedure for the parameters is
      presented and its properties are studied in a small simulation study. This model
      is applied to breast cancer incidence data of Swedish twins. The proportion of
      women susceptible to breast cancer is estimated to be 15 per cent.

PMID- 19856277
TI  - A comparison of methods for the construction of confidence interval for relative
      risk in stratified matched-pair designs.
AB  - A stratified matched-pair study is often designed for adjusting a confounding
      effect or effect of different trails/centers/ groups in modern medical studies.
      The relative risk is one of the most frequently used indices in comparing
      efficiency of two treatments in clinical trials. In this paper, we propose seven
      confidence interval estimators for the common relative risk and three
      simultaneous confidence interval estimators for the relative risks in stratified
      matched-pair designs. The performance of the proposed methods is evaluated with
      respect to their type I error rates, powers, coverage probabilities, and expected
      widths. Our empirical results show that the percentile bootstrap confidence
      interval and bootstrap-resampling-based Bonferroni simultaneous confidence
      interval behave satisfactorily for small to large sample sizes in the sense that
      (i) their empirical coverage probabilities can be well controlled around the pre
      specified nominal confidence level with reasonably shorter confidence widths; and
      (ii) the empirical type I error rates of their associated test statistics are
      generally closer to the pre-specified nominal level with larger powers. They are
      hence recommended. Two real examples from clinical laboratory studies are used to
      illustrate the proposed methodologies.

PMID- 19856278
TI  - One-pot protection and activation of amino acids using pentafluorophenyl
      carbonates.
AB  - Protection of the amino group and activation of the carboxylic acid groups are
      the most important steps associated with any peptide synthesis protocol; hence, a
      one-pot process to achieve these is highly desirable. A possible strategy is to
      use pentafluorophenyl carbonates to simultaneously protect the amino group as a
      carbamate derivative and activate the carboxylic acid group as a
      pentafluorophenyl ester. A detailed study is carried out to understand the scope
      and limitations of this method using five different pentaflurophenyl carbonates.
      The efficiency of these one-pot reactions depends largely on the nature of the
      pentafluorophenyl carbonates and also on the nature of the amino acids. Electron
      deficient and sterically less demanding carbonates reacted faster than the
      others, whereas amino acids with longer aliphatic side chains gave better yields
      than more polar amino acids.

PMID- 19856279
TI  - Assessment of risks by predicting counterfactuals.
AB  - Risk assessment is fundamental to most epidemiological and biomedical
      investigations. In this article, risks are assessed in terms of risk difference
      and risk ratio by predicting counterfactual outcomes. Models considered for
      binary outcomes are probit, logistic, and extreme-value regressions. New
      confidence intervals for the effect measures are proposed using the method of
      variance estimates recovery, and evaluated by a simulation study. A SAS macro is
      provided for the calculations. A risk ratio obtained using counterfactuals is
      also compared in the simulation with that directly estimated from the modified
      Poisson model to answer a recent concern about the validity of the latter
      approach. Two examples are used to illustrate the methods.

PMID- 19856280
TI  - Staurosporine-induced apoptosis of immortalized mouse proximal tubule cells is
      modulated by bcl-2 expression level.
AB  - Mouse terminal proximal tubule (S3)cells treated with staurosporine (STS)
      underwent morphological and biochemical changes characteristic of apoptosis.
      Treatment of S3 cells with STS, H-7, PMA, herbimycin A or genistein caused DNA
      fragmentation. STS inhibited the activity of protein kinase C but not of cdc-2
      kinase in S3 cells. No change in cell cycle distribution was observed in S3 cells
      treated with STS. However, treatment of S3 cells with STS resulted in a decrease
      in the level of bcl-2 mRNA expression in the cells. Overexpression of bcl-2
      inhibited the degree of STS-induced apoptosis of S3 cells. In conclusion, STS
      induces apoptosis of mouse S3 cells via inhibition of various protein kinases
      including protein kinase C, and the apoptosis is modulated by the bcl-2
      expression level.

PMID- 19856281
TI  - Heterogeneous nuclear RNP protein A1-arginine methylation during HCT-48 cell
      cycle.
AB  - Protein methylase I (protein-arginine N-methyltransferase) was examined in HCT-48
      cells, synchronized by serum deprivation and hydroxyurea treatment. The enzyme
      activity to methylate the added hnRNP protein A1 increased about 2-fold from G0
      to S phase, and then decreased during G2/M phase. The enzymatically [methyl-3H]
      labeled hnRNP protein A1 was identified by SDS-PAGE/fluorography, and the
      products were identified as NG-monomethylarginine and NG,NG-dimethyl
      (asymmetric)arginines by HPLC. Among endogenous proteins, the 20-kDa species in
      the extract was most intensely [methyl-3H]-labeled. This 20-kDa methylation was
      markedly inhibited by the addition of exogenous hnRNP protein A1, indicating that
      these two substrates compete for the same protein methylase. The possible role of
      this post-translational modification has been discussed.

PMID- 19856282
TI  - Interactions between heparinoids and alcohol dehydrogenase.
AB  - The interaction between polysulfated polysaecharides (low-molecular-weight
      heparin LMWH, dextran sulfate DS and pentosan sulfate PS) and yeast alcohol
      dehydrogenase (YADH) was investigated. The fluorescence and UV spectra of YADH
      after adding the tested polysaccharides have confirmed the interaction between
      the enzyme and these compounds. Kinetic studies have shown that LMWH, DS and PS
      are inhibitors of YADH (mixed type with respect to NAD). The most potent
      inhibitor is PS (ID50=37.5 ng/ml, Ki=0.6 muM). The inhibition effect depends on
      the ionic strength (the inhibition decreased by about 50% in the presence of 100
      mM Na2SO4) and pH value (the inhibition decreased at pH>7). The results indicate
      that the inhibition effect of these polyanions is caused by their electrostatic
      interactions with the NAD-binding region of YADH.

PMID- 19856284
TI  - Studies on the catalytic activity of human hepatic porphobilinogen deaminase.
AB  - Porphobilinogen deaminase was purified from human hepatocytes. A variety of group
      specific reagents have been used to achieve site-specific modifications to
      evaluate the potential role of such groups in the whole catalytic cycle.
      Treatment with dicarbonyl reagents caused a rapid loss in activity that was time
      and concentration, dependent. Protection experiments revealed that arginine
      residues are involved in the binding of the substrate. Treatment with Woodward's
      reagent K showed the fastest inactivation of deaminase (85% in 30 sec at 30mM)
      which was pH dependent and could be prevented by the presence of substrate,
      suggesting that deprotonated carboxylated groups from Asp/Glu are essential for
      catalytic activity. Kinetic analysis gave values of 0.3 sec-1 for the k3 rate
      constant and 8x10-2 M for the KI of the non covalent complex between deaminase
      Woodward's Reagent K.

PMID- 19856283
TI  - Study of peptide-protein interaction by high-performance liquid chromatography.
      Effect of hydrophobic and steric parameters.
AB  - The interaction of 16 peptides was studied on zein-coated silica column by high
      performance liquid chromatography. The separation factor, theoretical plate
      number and the asymmetry factors of the peaks were calculated. Stepwise
      regression analysis was applied to study the peptide-protein interactions and to
      find the molecular substructures involved in the interactions and to define their
      character. Zein-coated silica column was suitable for the determination of
      peptide-protein interaction and the investigated peptide-protein interactions
      were found to be mixed (hydrophobic and steric) character.

PMID- 19856285
TI  - Effect of dihydralazine on the fluidity of erythrocyte membranes.
AB  - Dihydralazine, a drug used in the treatment of chronic hypertension was found to
      affect the mobility of fatty acid hydrocarbon chains followed by spin-labelling
      technique with the use of 5-, 12- and 16-doxylstearate. The effect of this drug
      on the membrane bilayer properties may result either from the reduction of the
      number of double bonds in fatty acid hydrocarbon chains, as was shown by the
      changes of d1/d and order parameters in the region of C(12) or from direct
      interactions of the drug with the polar head group region of the phospholipids as
      was shown by changes in the distance between nitroxyl groups without changes of
      the order parameter in the region of C(5).

PMID- 19856286
TI  - Inhibition of various isoforms of rat liver glutathione S-transferases by tannic
      acid and butein.
AB  - Glutathione S-transferases (EC.2.5.1.18, GSTs) were purified from rat liver by S
      hexylglutathione affinity chromatography and six isoforms, namely C-1, C-2, C-3,
      C-4, A-2 and A-1, were isolated by CM-cellulose and DEAE-cellulose ion-exchange
      columns. Tannic acid and butein showed varying degrees of inhibition on the six
      individual GST isoforms. When 1-chloro-2,4-dinitrobenzene (CDNB) was used as a
      substrate, butein exerted significantly more potent inhibition on the cationic
      isoforms C-2, C-3 and C-4 with IC50 values of 6.8, 8.5 and 8.0 muM respectively.
      All the isoforms showed lower activity towards p-nitrobenzyt chloride when
      compared to CDNB and inhibition of the p-nitrobenzyl chloride-activity by tannic
      acid and butein was also weaker. The inhibitory effects of tannic acid and butein
      on each isoform decreased generally with increasing pH in the range of 6.0 to
      8.0. The optimum pHs for inhibitions by tannic acid and butein on the six
      individual isoforms lie in the pH range of 6.0 to 6.5.

PMID- 19856287
TI  - The histidine-805 in motif-C of the phage SP6 RNA polymerase is essential for its
      activity as revealed by random mutagenesis.
AB  - In order to identify functional residues of the bacteriophage SP6 RNA polymerase,
      its C-terminal one-twelfth region was randomly mutagenized using polymerase chain
      reactions of its gene under the conditions for reduced fidelity of Taq DNA
      polymerase. Using a two-vector system that permits phenotypic isolation of
      mutants with reduced in vivo transcription activity, 3 single and 1 multiple
      mutants were isolated. A single substitution of Gln for His805 resulted in
      complete inactivation of the enzyme. A multiple mutant carrying substitutions at
      808, 820, 835, 843 and 848 also abolished the activity. However, changes of
      Pro856-->Ser and Asp862-->Glu individually reduced the activity only slightly. It
      is noteworthy that His805 is one of the two motif-C residues that are absolutely
      conserved among all the DNA polymerases and monomeric RNA polymerases.

PMID- 19856288
TI  - The activity of branched-chain alpha-keto acid dehydrogenase complex in rat
      digestive tracts: Effects of dietary protein and exercise.
AB  - Branched-chain alpha-keto acid dehydrogenase complex is the rate limiting enzyme
      in catabolism of branched-chain amino acids. In this study, we examined effects
      of dietary protein and exercise on the complex activity in digestive tracts
      (stomach, small intestine and colon) of rats. Rats were fed a high (30%) or low
      (8%) protein diet for 3 weeks and a half of rats in each diet group was exercised
      by 85 min running just prior to sacrifice on the final day of the experiment.
      Total and actual (active form) activities of the complex were markedly high in
      stomach compared to other two tissues and the actual activity in stomach was
      significantly elevated by exercise only in rats fed the high protein diet. Both
      total and actual activities in colon were only a few percentage of those in
      stomach, and those in small intestine was further less. These results suggest
      that rat stomach is the tissue active in catabolism of branched-chain amino
      acids, which is promoted by combination of high protein diet and exercise.

PMID- 19856289
TI  - Recombinant CTFR detection in CF tracheal epithelial cells following in vitro
      liposomeme-mediated gene transfer.
AB  - The efficacy of CFTR gene transfer mediated by cationic liposomes Dc-Chol/DOPE
      into cystic fibrosis (CF) tracheal epithelial cells carrying defective processing
      mutations (S549N/N1303K), was assessed by studying mRNA and protein expression of
      the recombinant product. Appreciable levels of mRNA transcripts were detected 48
      h after transfection, while complete translocation of the recombinant CFTR to the
      apical membrane of epithelial cells was observed after 72 h following
      transfection. Our results suggest that in vitro restoration of a normal CFTR
      processing and migration to the cell plasmalemma requires 72 h at least as
      demonstrated by immunocyto-fluorescence using the monoclonal antibody MATG 1016.
      These findings are relevant onto gene transfer phase I clinical studies.

PMID- 19856290
TI  - An optical biosensor study of the interaction parameters and role of hydrophobic
      tails of cytochrome P450 2B4, b5 and NADPH-flavoprotein in complex formation.
AB  - The real-time interactions of membrane proteins - cytochrome P450 2B4, NADPH
      cytochrome P450 reductase and cytochrome b5 - were studied by use of an optical
      biosensor system. The association and dissociation rate constants for the
      individual complexes were measured and the affinities of the redox partners for
      each other were estimated. The association rate constants of these complexes were
      found to be close to the diffusion limit and their dissociation rate constants
      were in the order of 1s-1. A dominant role of the interaction of the membraneous
      hydrophobic fragments in the formation of productive electron transferring
      complexes between the proteins was demonstrated.

PMID- 19856291
TI  - Cytotoxic activity of acetylcholine receptor ligands.
AB  - Acetylcholine receptor ligands were studied for cytotoxicity in K562 human
      erythroid leukemia tumor cells. Cytotoxicity of carbachol, an agonist of
      acetylcholine receptors, atropine, an antagonist of muscarinic acetylcholine
      receptor, neurotoxin 11 (NT II) from Naja naja oxiana cobra venom and
      tubocurarine, antagonists of acetylcholine receptor of nicotinic type was
      exhibited in the 10-7-10-5 M concentration range. Several cytolytic processes,
      two for carbachol and three for other ligands, corresponding to different
      concentrations of each ligand were detected. All acetylcholine receptor ligands
      induced internucleosomal DNA fragmentation.

PMID- 19856292
TI  - Production and characterisation of monoclonal and polyclonal amtobpdoes agaomst
      bovine osteocalcin.
AB  - Monoclonal and polyclonal antibodies were produced against osteocalcin purified
      from bovine bone. The antibodies were used for the development of a two-site
      ELISA. A monoclonal antibody recognising residues 15-49 of bovine osteocatcin
      generated by cleavage with 70% formic acid was used as capture antibody and a
      biotinylated polyclonal antibody recognising the same peptide was used for
      detection. The two-site assay did not detect any tryptic peptides of bovine
      osteocalcin (residues 1-19, 20-43, and 45-49) nor did it detect the peptide 1-14
      or the synthetic peptide 37-49. Cross-reaction was observed for osteocalcin in
      plasma from sheep, goat, chicken and human but not for osteocalcin from rat and
      pig.

PMID- 19856293
TI  - Protoporphyrin IX potentiates horseradish peroxidase-catalyzed oxidation of
      NADH:Involvement of enzyme-porphyrin interaction.
AB  - Protoporphyrin IX potentiates horseradish peroxidase-catalyzed hydrogen peroxide
      mediated NADH oxidation, but the porphyrin cannot change the enzyme-catalyzed o
      dianisidine oxidation. Spectrofluorimetric studies reveal that an interaction
      occurs between horseradish peroxidase and protoporphyrin IX. The interaction is
      predominantly hydrophobic and entropy-driven endothermic process. This
      interaction may influence the potentiation effect of the protoporphyrin IX on
      horseradish peroxidase-catalyzed NADH oxidation because the latter has a positive
      correlation with the extent of binding of the protein with the porphyrin.

PMID- 19856294
TI  - The structural analysis of the O-glycans of the jacalin-bound rabbit
      immunoglobulin G.
AB  - Rabbit immunoglobulin G (IgG) is a sialoglycoprotein (2.4% carbohydrate),
      containing both N-glycolyl (Neu5Gc) and N-acetyl (Neu5Ac) neuraminic acids in a
      ratio of 87:13. A small fraction of rabbit IgG (about 25% of total IgG) bound to
      jacalin as demonstrated by affinity chromatography. The jacalin-bound rabbit IgG
      contained O-linked glycans which were liberated from the protein by beta
      elimination and isolated. Two O-glycan structures were determined by 1H-NMR
      spectroscopy, as being Neu5Gc(alpha2-3)-Gal (beta31-3)-GalNAc-ol and
      Neu5Ac(alpha2-3)-Gal(beta1-3)-GalNAc-ol in a ratio of 83...n17.

PMID- 19856295
TI  - Reversible cell cycle arrest with concomitant p21/WAF1 overexpression and
      mitochondrial destruction by nitric oxide.
AB  - When human hepatocellular carcinoma Hep-G2 cells were treated with the NO
      generating compounds, S-nitroso-N-acetyl-DL-penicillamine(SNAP) or (+/-)-(E)-4
      ethyl-2-(E)-hydroxyimino]-5-nitroso-3-hexenamide, cells stopped growing. Most
      cells were found to be in either G1 or G2/M phase and the dye-exclusion test
      revealed that the cells were alive. Electron microscopic examination confirmed
      the integrity of cells and nuclei. Nuclear staining with the DNA-binding dye
      H33258 revealed that cells did not undergo apoptosis although dramatic changes in
      mitochondrial morphology were noticed within 6 hr of treatment with SNAP by
      electron microscopy. Western and northern blot analysesrevealed that cells
      overexpressed p21/WAF1. The growth arrest was released by withdrawal of the NO
      generating compound and cells started to divide within 24 hr after withdrawal of
      the compounds.

PMID- 19856296
TI  - A protease from the marine sponge Callyspongia schulzi.
AB  - Aqueous extracts of 25 marine sponge species (from coral reefs of Papua New
      Guinea) were screened for proteolytic activity. Only one sponge, Callyspongia
      schulzi, showed remarkable activity. A protease hydrolyzing casein as well as the
      synthetic substrate alpha-N-benzoyl-L-arginine ethyl ester was isolated from the
      sponge extract by gel filtration, ion-exchange and HPLC absorption
      chromatography. The enzyme was homogenous in SDS-PAGE exhibiting an apparent
      molecular weight of 80 kDa. Its pH optimum was in the range of 9-11, it was
      remarkably heat-stable and was not inhibited by phenylmethane sulfonylfluoride,
      soybean trypsin inhibitor, aprotinin or alpha1-antitrypsin, but by EDTA and 1,10
      phenanthroline suggesting properties of a metalloprotease. The protease
      hydrolyzed the oxidized insulin B-chain between Arg22-Gly23 and Lys29-Ala30,
      similar to trypsin.

PMID- 19856297
TI  - Mutational analysis for the role of C-terminal region of ecotin, a dimeric
      inhibitor of pancreatic serine proteases.
AB  - Ecotin is a dimeric molecule that is capable of inhibiting a variety of serine
      proteases. To clarify the role of the C-terminal region, mutagenesis was
      performed to delete the C-terminal residues from 130 to 142. The mutant inhibitor
      behaved as a monomer upon cross-linking analysis followed by gel filtration. The
      mutation also resulted in a significant increase of the Ki of ecotin on trypsin,
      chymotrypsin, and elastase (i.e., by 1 to 2 order of magnitude). The mutant
      ecotin was slightly more sensitive to heating at 100 degrees C than the wild-type
      ecotin, but became much more sensitive to the heat treatment upon reduction of
      the intra-chain disulfide bond in its subunits. In addition, treatment with 4 M
      urea resulted in complete loss of the activity of the mutant ecotin but not that
      of the wild-type inhibitor. Thus, the C-terminal region of ecotin seems to be
      required not only for dimerization of the subunits but also for optimal
      interaction with target proteases and for maintenance in its structural
      stability, particularly under reducing or denaturing conditions.

PMID- 19856298
TI  - Age- and Tissue-specific regulation of chicken inorganic pyrophosphatase.
AB  - The activities and hormone regulatory patterns of inorganic pyrophosphatase
      (PPiase) of male Rhode Island Red (RIR) chickens were studied at two different
      postnatal ages (5- and 90-day). The endogenous activity level was found to be
      significantly higher in the immature (5-day) groups for all the tissues (liver,
      kidney and brain) studied as compared to that of mature (90-day). Hydrocortisone
      (HC) administration significantly inhibited the PPiase activity in the immature
      chicken liver and did not affect the enzyme in kidney and brain at either age. In
      contrast, insulin increased significantly the activity of PPiase in the liver of
      immature chicken. Kidney PPiase, however, was unaffected to insulin treatment at
      immature age, while it showed increased activity in mature group. On the other
      hand, brain PPiase activity was significantly increased at both the ages studied.
      These findings indicate an age- and tissue-specific regulation of PPiase activity
      by hydrocortisone and insulin in chicken.

PMID- 19856299
TI  - The priming effects of some human interleukins on the production of leukotrienes
      by calcium ionophore stimulated leukocytes.
AB  - This study demonstrates the changing levels of leukotrieneB4 (LTB4) and
      leukotrieneC4 (LTC4) generated by human white blood cells primed with different
      human interleukins IL-3, IL-5, IL-6, IL-8 and with human hematopoietic growth
      factor granulocyte-macrophage colony stimulating factor (GM-CSF). Preincubation
      of white blood cells at 37 degrees C for 30 min with different human interleukins
      significantly increased leukotriene production in white blood cells preincubated
      with diluent control while IL-3 was without priming effects. Addition of
      exogenous arachidonic acid to non primed white blood cells increased the
      production of leukotrienes in response to the calcium ionophore (A23187). The
      enhancement of the leukotrienes production by white blood cells stimulated by
      A23187 was only observed when the cells stimulated for periods of 2 min or less.
      The results reveal that GM-CSF, IL-4, IL-6 and IL-8 belong to particular set of
      cytokines with potent modulating effect on inducing inflammatory mediators
      released by white blood cells, while IL-3 was ineffctive.

PMID- 19856300
TI  - Efficient production of active TNF-alpha by albumin signal peptide.
AB  - TNF-alpha is initially synthesized as a membrane-anchored precursor protein and
      processed proteolytically by a matrix metalloproteinase (MMP)-like enzyme. In
      order to establish an efficient expression system of TNF-alpha in mammalian cells
      without involvement of the extracellular enzyme, an expression plasmid (pCN-alb
      TNF) was constructed with a signal sequence of the rat albumin gene as a module
      for secretion. The highest level of production of TNF-alpha was observed in the
      clone CT-3 by SDS-PAGE and Western blot analysis. Biological activity of the
      secretion was revealed by repression of catalase gene expression in hepatoma
      cells and cytotoxity to L929 cells. Attachment of the signal peptide to mature
      form resulted in the enhancement of production of the cytokine.

PMID- 19856301
TI  - Quantification of epididymal retinoic acid-binding protein (ERABP) mRNA in
      different anatomical regions of the adult rat epididymis.
AB  - Epididymal retinoic acid-binding protein (ERABP), an 18.5 Kd androgen-dependent
      protein, is synthesized and secreted by the rat epididymis. The concentration of
      ERABP mRNA in different anatomical regions of the rat epididymis was measured
      using quantitative reverse transcription polymerase chain reaction (RT-PCR) and
      Northern blot analysis. While quantitative differences in the level of ERABP were
      observed in the caput region of the epididymis, no detectable levels of ERABP
      mRNA was observed in the corpus and cauda regions of the epididymis. In the caput
      region of the epididymis, 0.22 ng and 0.036 ng mRNA/gg of total RNA were measured
      in the proximal and distal segments of the caput region, respectively. These
      results indicate that ERABP is differentially expressed in the rat epididymis and
      suggest that the protein may be regulated at the level of transcription.

PMID- 19856302
TI  - Expression or possession of catalase gene does not alter the capacity of M.
      smegmatis to survive within human macrophages.
AB  - Mycobacterium tuberculosis genes are expressed and screened in Mycobacterium
      smegmatis as a host, hence their survival in human monocytes needs to be
      determined. Strains of Mycobacterium smegmatis with an inactive catalase
      peroxidase gene (KatG), or into which the KatG gene of Mycobacterium tuberculosis
      had been transfected, were used to study the influence of catalase on
      intracellular mycobacterial survival within human monocyte-derived macrophages.
      The five strains of Mycobacterium smegmatis were observed to grow at similar
      rates, irrespective of their catalase phenotype, within IFNgamma-treated or
      untreated human macrophage cultures, over a 3 day infection period. Moreover,
      there was no differential pattern of growth or inhibition among the strains of
      Mycobacterium smegmatis studied.

PMID- 19856303
TI  - Stability of assembled epitopes on human chorionic gonadotropin to covalent
      modifications.
AB  - A measure of stability of a given epitope is an important parameter in the
      exploration of the utility of a desired MAb. It defines the conditions necessary
      for using MAbs as an investigative tool in several research methodologies and
      therapeutic protocols. Despite these obvious interests the lack of simple and
      rapid assay systems for quantitating MAb-Ag interactions has largely hampered
      these studies. A single step MAb-Solid Phase Radioimmunoassay (SS-SPRIA), is
      described which eliminates errors that may arise with multistep sandwich assays.
      SS-SPRIA has been used to demonstrate the differential stability of the assembled
      epitopes on gonadotropins. Differential stability towards specific reagents can
      be exploited to identify aminoacid residues at the epitopic site. Inactivation of
      an epitopic region is indicative of the presence of the group modified, provided
      conformational relaxations are not induced due to modifications at distant sites.
      Here we provide evidence to validate these conclusions.

PMID- 19856304
TI  - Flexible modeling of longitudinal highly skewed outcomes.
AB  - The analysis of data from epidemiologic and environmental studies presents
      challenges such as skewness of distribution, rounding and multiple measurements
      over time. To model trends over time based on repeated measurements, we propose a
      general latent model suitable for highly skewed data. The model assumes that the
      observed outcome is determined by an unobservable outcome that follows a Weibull
      distribution. To accommodate correlations among repeated responses over time, we
      introduce a general random effect from the power variance function (PVF) family
      of distributions, including the gamma distribution often employed in the
      literature. The resulting marginal likelihood has a closed form without resorting
      to numerical or approximation methods. We study estimation and hypothesis testing
      under these models, with different choices of random effect distributions.
      Simulation studies are conducted to evaluate their performance. Finally, we apply
      the proposed method to exposure data collected from the Michigan polybrominated
      biphenyl (MIPBB) study.

PMID- 19856305
TI  - Chemoradiation for patients with advanced oral cavity cancer.
AB  - OBJECTIVES/HYPOTHESIS: Patients with advanced oral cavity cancer (OCC) typically
      have not been enrolled in clinical trials utilizing contemporary multimodality
      strategies. There exist dogmatic expectations of inferior outcome in OCC patients
      secondary to ineffectiveness of treatment and unacceptable toxicity. The purpose
      of this study was to analyze survival, swallowing function, and incidence of
      osteoradionecrosis (ORN) of patients with stage III/IV OCC who have undergone
      primary concomitant chemoradiotherapy (CRT). METHODS: All advanced OCC patients
      who were enrolled in University of Chicago concomitant CRT protocols from 1994 to
      2008 were reviewed. One hundred eleven newly diagnosed advanced OCC patients were
      evaluated. We performed a subset analysis of 27 additional advanced OCC patients
      who underwent surgery followed by postoperative CRT. Swallowing function was
      assessed via oropharyngeal motility study, and a Swallowing Performance Status
      Scale score was assigned. Presence of clinically significant ORN was documented.
      RESULTS: Median follow-up was 3.25 years. Five-year overall and progression-free
      survival was 66.9% and 65.9%, respectively. There was no difference in overall or
      progression-free survival when the surgery-first group was compared with the
      primary CRT group (P = .88 and P = .86 respectively). Function, without gastric
      tube requirement, was excellent, with 92.2% of patients able to maintain weight
      via oral route. Incidence of ORN was 18.4%, occurring in nine of 49 patients
      evaluated. CONCLUSIONS: Our data support the use of primary CRT as a viable
      treatment option for patients with advanced OCC. Survival is high, and overall
      function for the majority of patients is satisfactory. Patients with T4 oral
      tongue cancer may be spared total glossectomy. The incidence of ORN may be
      considered acceptable, in light of the benefits of enduring life and function.

PMID- 19856306
TI  - Database of misidentified cell lines.

PMID- 19856308
TI  - The role of human papillomavirus in the increased incidence of base of tongue
      cancer.
AB  - Numerous reports have shown that the incidence for oropharyngeal cancer is
      increasing and that human papillomavirus (HPV) is a risk factor. However, few
      studies have investigated the specific subsites of the oropharynx. Following our
      previous research on tonsillar cancer, we assessed the increase in the incidence
      of base of tongue cancer and the prevalence of HPV in this disease. Between 1998
      and 2007, 109 patients were diagnosed for base of tongue cancer in Stockholm
      county. Ninety-five paraffin-embedded diagnostic tumor biopsies from patients
      were obtained and tested for HPV, both by general HPV PCR and HPV-16/HPV-33 type
      specific PCR. Expression of HPV-16 RNA was analyzed to confirm E6 and/or E7
      expression. Incidence data were obtained from the Swedish Cancer Registry. An
      overall increase in the incidence of base of tongue cancer from 0.15/100,000
      person-years during 1970-1974 to 0.47/100,000 person-years during 2005-2007 was
      found in Sweden. The prevalence of HPV in base of tongue cancer in Stockholm
      county increased from 58% during 1998-2001 to 84% during 2004-2007 (p < 0.05). In
      the HPV-positive tumors, HPV-16 dominated (86%) but interestingly, HPV33 was
      detected in as many as 10%. E6 and/or E7 RNA were found in 85% of the samples
      tested. The incidence of base of tongue cancer, as well as the proportion of HPV
      positive tumors, has increased in Sweden during the study period, suggesting that
      HPV may contribute to this increase.

PMID- 19856307
TI  - Synergism from combined immunologic and pharmacologic inhibition of HER2 in vivo.
AB  - The monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor
      lapatinib improve the clinical outcome of patients with HER2-overexpressing
      breast cancer. However, the majority of metastatic cancers will eventually
      progress, suggesting the need for other therapies. Because HER2 overexpression
      persists, we hypothesized that the anti-HER2 immune response induced by cancer
      vaccines would be an effective strategy for treating trastuzumab- and lapatinib
      refractory tumors. Furthermore, we hypothesized that the antibody response could
      synergize with lapatinib to enhance tumor inhibition. We developed a recombinant
      adenoviral vector expressing a kinase-inactive HER2 (Ad-HER2-ki) to use as a
      cancer vaccine. Vaccine-induced polyclonal HER2-specific antiserum was analyzed
      for receptor internalization and signaling effects alone and in combination with
      lapatinib. Ad-HER2-ki vaccine-induced potent T cell and antibody responses in
      mice and the vaccine-induced polyclonal HER2-specific antiserum mediated receptor
      internalization and degradation much more effectively than trastuzumab. Our in
      vitro studies demonstrated that HER2 vaccine-induced antibodies effectively
      caused a decrease in HER2 expression, but when combined with lapatinib caused
      significant inhibition of HER2 signaling, decreased pERK and pAKT levels and
      reduced breast tumor cell proliferation. In addition, a known mechanism of
      resistance to lapatinib, induction of survivin, was inhibited. The combination of
      Ad-HER2-ki plus lapatinib also showed superior antitumor efficacy in vivo. Based
      on these results, we feel clinical studies using this approach to target HER2
      overexpressing breast cancer, including trastuzumab- and lapatinib-resistant
      tumors is warranted.

PMID- 19856309
TI  - Fetal cell microchimerism in papillary thyroid cancer: studies in peripheral
      blood and tissues.
AB  - Fetal cell microchimerism (FCM) is defined as the persistence, for decades after
      pregnancy, of fetal cells in maternal organs and circulation without any apparent
      rejection. We recently reported evidence, in papillary thyroid cancer (PTC)
      tissues, supporting a possible role of FCM in tumor damage and repair. To extend
      those data at the peripheral level, 106 women with a previous male pregnancy,
      comprising 57 with PTC and 49 healthy controls were enrolled. The presence of
      circulating male DNA was assessed by the amplification of the Y chromosome
      specific gene SRY, with a sensitivity of 1 male cell per 1 million female cells.
      Moreover, to compare the microchimeric status in blood and in tumors, the
      neoplastic tissues of 19 women were studied. At the blood level, a significantly
      lower frequency of FCM was found in parous women with PTC with respect to
      controls (49.1% vs. 77.6%; p = 0.002). By PCR, male DNA was identified in the
      tumor tissues of 6 patients, and FISH analyses confirmed the presence of
      microchimeric cells (range 2.1-6.9 cells/section). In some patients, FCM was
      negative in the blood, whereas microchimeric cells were identified in the tumor.
      In conclusion, the prevalence of FCM in peripheral blood was found to be
      significantly lower in patients than in healthy controls. The presence of
      microchimeric cells in the tumors, but not at the peripheral level, supports the
      hypothesis that fetal cells could reside in maternal niches and could be
      recruited to diseased areas, where they could differentiate to regenerate damaged
      tissues.

PMID- 19856310
TI  - SMAD4: a predictive marker of PDAC cell permissiveness for oncolytic infection
      with parvovirus H-1PV.
AB  - Pancreatic ductal adenocarcinoma (PDAC) represents the eighth frequent solid
      tumor and fourth leading cause of cancer death. Because current treatments
      against PDAC are still unsatisfactory, new anticancer strategies are required,
      including oncolytic viruses. Among these, autonomous parvoviruses (PV), like MVMp
      (minute virus of mice) and H-1PV are being explored as candidates for cancer gene
      therapy. Human PDAC cell lines were identified to display various
      susceptibilities to an infection with H-1PV. The correlation between the
      integrity of the transcription factor SMAD4, mutated in 50% of all PDAC, and H
      1PV permissiveness was particularly striking. Indeed, mutation or deletion of
      SMAD4 dramatically reduced the activity of the P4 promoter and, consequently, the
      accumulation of the pivotal NS1 protein. By means of DNA affinity immunoblotting,
      novel binding sites for SMAD4 and c-JUN transcription factors could be identified
      in the P4 promoter of H-1PV. The overexpression of wild-type SMAD4 in deficient
      cell lines (AsPC-1, Capan-1) stimulated the activity of the P4 promoter, whereas
      interference of endogenous SMAD4 function with a dominant-negative mutant
      decreased the viral promoter activity in wild-type SMAD4-expressing cells (Panc
      1, MiaPaCa-2) reducing progeny virus production. In conclusion, the importance of
      members of the SMAD family for H-1PV early promoter P4 activity should guide us
      to select SMAD4-positive PDACs, which may be possible targets for an H-1PV-based
      cancer therapy.

PMID- 19856311
TI  - Betapapillomavirus infection profiles in tissue sets from cutaneous squamous cell
      carcinoma patients.
AB  - Human papillomaviruses from the genus beta (betaPV) are a possible cause of
      cutaneous squamous cell carcinoma (SCC). We compared the betaPV infections in SCC
      and in sets of cutaneous tissues collected from a series of individual SCC
      patients to determine concordance and to assess the adequacy of eyebrow hairs as
      noninvasive markers of betaPV infection. Biopsies of SCC tumors, perilesional
      tissue, normal skin from the mirror image of nonfacial SCC and plucked eyebrow
      hairs were collected from 21 patients with incident SCC living in Queensland,
      Australia. These were tested for the presence of DNA from 25 different betaPV
      types. Overall prevalence of betaPV was high in every sample type, ranging from
      81% to 95%. The median number of types was significantly higher in the SCC tumour
      (6), perilesional skin (5) and eyebrow hairs (5) than in normal skin (2).
      Comparing SCC tissue with other sample types within patients showed 63
      overlapping infections with eyebrow hairs (71%; 95% CI: 60-80); 56 with
      perilesional skin samples (63%; 95% CI: 52-73) and 23 with normal skin samples
      (26%; 95% CI: 17-36). The sensitivity of eyebrow hair testing for detection of
      betaPV in the tumor was 82% (95% CI: 57-96) with concordance defined as 50% of
      betaPV types in common and 29% (95% CI: 10-56) for 100% concordance. These
      findings support the concept that perilesional skin represents an area of field
      change involving betaPV preceding SCC development and indicate that eyebrow hairs
      can serve to some degree as an easily collected marker of tumor betaPV status in
      epidemiological studies.

PMID- 19856312
TI  - Rapamycin enhances chemotherapy-induced cytotoxicity by inhibiting the
      expressions of TS and ERK in gastric cancer cells.
AB  - We have previously reported the synergistic cytotoxic effects of Docetaxel (TXT)
      and S-1 in gastric cancer in vitro and in vivo, and the combination regimen is
      now under phase III clinical trail. In this study, to elucidate whether the
      rapamycin, the inhibitor of the mTOR (mammalian target of rapamaycin), can
      enhance the potentiation of TXT and 5-fluorouracil (5-Fu) in gastric carcinoma
      cells. Rapamycin inhibited the growth of TMK-1, MKN-28, MKN-45 and MKN-74 cell
      lines by MTT assay, and it demonstrated the cytostatic effects as G1 arrest shown
      by flowcytometry. However, the cytotoxic effects of 5-Fu, TXT and cisplatin were
      enhanced by 2 to 4 times with the concomitant administration of rapamycin. To
      clarify the mechanism of the potentiation, the expression changes of the enzymes
      relating DNA metabolism and cell growth signal transduction pathways were
      examined by western blot analysis. Interestingly, the expression of thymidilate
      synthase was markedly decreased by the administration of rapamycin in TMK-1 cells
      in a time- and dose-dependent manner. Moreover, rapamycin decreased the
      phosphorylation of 4E-BP1, the phosphorylation of ERK1/2 and enhanced the
      phosphorylation of c-Jun NH2-terminal kinase, and the activation of caspase of
      apoptotic pathways in combination with TXT. These results strongly indicate that
      the mTOR inhibitor can enhance the potentiation of TXT and 5-Fu or S-1 and can
      serve as a new therapeutic tool for advanced and recurrent gastric cancer
      patients.

PMID- 19856313
TI  - High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts
      improved survival in mismatch repair-proficient colorectal cancer patients.
AB  - Regulatory T cells (T(reg)) inhibit the generation of host-versus-tumor immunity
      via suppression of tumor-specific effector T-cell responses and development of
      immune tolerance to neoplastic cells. The transcription factor forkhead box P3
      (FOXP3) is an intracellular key molecule for T(reg) development and function and
      is considered to represent the most specific T(reg) cell marker. The aim of this
      study was to analyze the frequency and prognostic impact of tumor-infiltrating
      FOXP3(+) T(reg) in colorectal cancer (CRC) stratified by mismatch-repair (MMR)
      status. Using the tissue microarray technique, 1,420 tumor samples were
      immunohistochemically stained for FOXP3 and stratified into 1,197 MMR-proficient
      and 223 MMR-deficient CRCs. Additionally, the 1,197 MMR-proficient CRCs were
      randomized into 2 subgroups (Test Groups 1 and 2; n = 613 and 584, respectively).
      In both MMR-proficient CRC subgroups high frequency tumor-infiltrating FOXP3(+)
      T(reg) was associated with early T stage (p = 0.001 and <0.001), tumor location
      (p = 0.01 and 0.045) and increased 5-year survival rate (p = 0.004 and <0.001),
      whereas in MMR-deficient CRCs an association between FOXP3(+) T(reg) and absence
      of lymph node involvement (p = 0.023), absence of vascular invasion (p = 0.023)
      and improved 5-year survival rate (p = 0.029) could be detected. In a
      multivariable analysis including age, gender, T stage, N stage, tumor grade,
      vascular invasion, and tumor border configuration, a high FOXP3(+) T(reg)
      frequency was an independent prognostic factor in both MMR-proficient CRC subsets
      (p = 0.019 and p = 0.007), but not in the MMR-deficient CRCs (p = 0.13).
      Therefore, high frequency of tumor-infiltrating FOXP3(+) T(reg) is associated
      with early T stage and independently predicts improved disease-specific survival
      in MMR-proficient CRC patients.

PMID- 19856315
TI  - Overexpression of IQGAP1 in advanced colorectal cancer correlates with poor
      prognosis-critical role in tumor invasion.
AB  - IQGAP1 is a multifunctional protein involved in actin cytoskeleton assembly and E
      cadherin-mediated cell adhesion. We reported previously IQGAP1 overexpression in
      human colorectal carcinomas especially at the invasion front (IF) and that such
      overexpression tended to correlate with lymph node metastasis in advanced cases.
      Thus, in this study, we investigated the clinicopathological significance of
      IQGAP1 expression in 85 cases of pT2-3 colorectal carcinomas with special
      reference to its expression pattern and prognosis, followed by analysis of the
      role of IQGAP1 in cancer invasion in vitro. Quantitative reverse transcription
      PCR showed significant upregulation of IQGAP1 in colorectal carcinomas compared
      with normal mucosa. Immunohistochemically, IQGAP1 expression pattern was
      classified into diffuse (20%), IF-associated (35.3%) and focal (44.7%). The
      diffuse pattern was associated with higher rates of distant metastasis. Patients
      with IQGAP1 overexpression and diffuse pattern had significantly shorter survival
      (p < 0.0001) than others, and the diffuse pattern was an independent predictor of
      poor survival by multivariate analysis. In vitro invasion assays using three
      human colon carcinoma cell lines showed that IQGAP1 siRNA significantly
      suppressed hepatocyte growth factor (HGF)-stimulated cell invasion. HGF reduced
      membranous localization of alpha-catenin, but did not alter localization of E
      cadherin, beta-catenin and IQGAP1 in membranes. Suppression of IQGAP1 expression
      by siRNA did not alter membranous localization of alpha-catenin even in the
      presence of HGF. Our results indicate that IQGAP1 plays a critical role in colon
      cancer cell invasion, and therefore diffuse and high expression of IQGAP1
      predicts poor prognosis in patients with colorectal carcinoma.

PMID- 19856314
TI  - Promoter demethylation and chromatin remodeling by green tea polyphenols leads to
      re-expression of GSTP1 in human prostate cancer cells.
AB  - Epigenetic silencing of gluthathione-S-transferase pi (GSTP1) is recognized as
      being a molecular hallmark of human prostate cancer. We investigated the effects
      of green tea polyphenols (GTPs) on GSTP1 re-expression and further elucidated its
      mechanism of action and long-term safety, compared with nucleoside-analog
      inhibitor of DNA methyltransferase (DNMT), 5-aza-2'-deoxycitidine. Exposure of
      human prostate cancer LNCaP cells to 1-10 microg/ml of GTP for 1-7 days caused a
      concentration- and time-dependent re-expression of GSTP1, which correlated with
      DNMT1 inhibition. Methyl-specific-PCR and sequencing revealed extensive
      demethylation in the proximal GSTP1 promoter and regions distal to the
      transcription factor binding sites. GTP exposure in a time-dependent fashion
      diminished the mRNA and protein levels of MBD1, MBD4 and MeCP2; HDAC 1-3 and
      increased the levels of acetylated histone H3 (LysH9/18) and H4. Chromatin
      immunoprecipitation assays demonstrated that cells treated with GTP have reduced
      MBD2 association with accessible Sp1 binding sites leading to increased binding
      and transcriptional activation of the GSTP1 gene. Exposure of cells to GTP did
      not result in global hypomethylation, as demonstrated by methyl-specific PCR for
      LINE-1 promoter; rather GTP promotes maintenance of genomic integrity.
      Furthermore, exposure of cells to GTP did not cause activation of the
      prometaststic gene S100P, a reverse response noted after exposure of cells to 5
      aza-2'deoxycitidine. Our results, for the first time, demonstrate that GTP has
      dual potential to alter DNA methylation and chromatin modeling, the 2 global
      epigenetic mechanisms of gene regulation and their lack of toxicity makes them
      excellent candidates for the chemoprevention of prostate cancer.

PMID- 19856317
TI  - Can physical activity modulate pancreatic cancer risk? a systematic review and
      meta-analysis.
AB  - Numerous epidemiological studies have examined the association between physical
      activity and pancreatic cancer; however, findings from individual cohorts have
      largely not corroborated a protective effect. Among other plausible mechanisms,
      physical activity may reduce abdominal fat depots inducing metabolic improvements
      in glucose tolerance and insulin sensitivity, thereby potentially attenuating
      pancreatic cancer risk. We performed a systematic review to examine associations
      between physical activity and pancreatic cancer. Six electronic databases were
      searched from their inception through July 2009, including MEDLINE and EMBASE,
      seeking observational studies examining any physical activity measure with
      pancreatic cancer incidence/mortality as an outcome. A random effects model was
      used to pool individual effect estimates evaluating highest vs. lowest categories
      of activity. Twenty-eight studies were included. Pooled estimates indicated a
      reduction in pancreatic cancer risk with higher levels of total (five prospective
      studies, RR: 0.72, 95% CI: 0.52-0.99) and occupational activity (four prospective
      studies, RR: 0.75, 95% CI: 0.59-0.96). Nonsignificant inverse associations were
      seen between risks and recreational and transport physical activity. When
      examining exercise intensity, moderate activity appeared more protective (RR:
      0.79, 95% CI: 0.52-1.20) than vigorous activity (RR: 0.97, 95% CI: 0.85-1.11),
      but results were not statistically significant and the former activity variable
      incorporated marked heterogeneity. Despite indications of an inverse relationship
      with higher levels of work and total activity, there was little evidence of such
      associations with recreational and other activity exposures.

PMID- 19856316
TI  - Low-risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer
      patients.
AB  - To validate common low-risk variants predisposing for breast cancer (BC) in a
      large set of BRCA1/2 negative familial or genetically enriched cases from
      Germany, we genotyped 1,415 cases and 1,830 healthy women by MALDI-TOF in 105
      candidate SNPs. Significantly higher ORs than previously reported for
      heterozygous unselected cases were found for the minor allele in FGFR2 (OR =
      1.43, 95% CI 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95%
      CI 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs
      for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% CI 1.68
      2.51, LSP1 (OR = 0.49, 95% CI 0.28-0.86) and TNRC9 (OR = 1.62, 95% CI 1.27-2.07).
      Moreover, the additional validation of 99 CGEMS-SNPs identified putative novel
      susceptibility alleles within the LSP1 gene (OR = 0.73, 95% CI 0.61-0.87, p-value
      = 5.23 x 10(-4)). Finally, we provide evidence for the first time that a low-risk
      variant located at 6q22.33 (rs6569479) is associated with estrogen receptor
      negative BC in familial cases (OR = 1.33, 95% CI 1.06-1.66; p-value = 0.012). Our
      data confirm the impact of the previously identified susceptibility loci and
      provide preliminary evidence for novel susceptibility loci in familial BC cases
      and correlate them to specific histopathological subtypes defined by estrogen
      receptor status.

PMID- 19856318
TI  - Prenatal diagnosis of brachytelephalangic chondrodysplasia punctata: case report.
AB  - Brachytelephalangic chondrodysplasia punctata is a rare congenital skeletal
      dysplasia. Within the heterogeneous group of chondrodysplasia punctata, the
      brachytelephalangic type is noteworthy because it has a better prognosis than do
      the other types. We report a case of brachytelephalangic chondrodysplasia
      punctata diagnosed by ultrasound imaging at 30 weeks' gestation; it was
      associated with polyhydramnios and a normal cervical spinal canal. Imaging
      features are described and differential diagnosis with other forms of
      chondrodysplasia punctata is discussed.

PMID- 19856319
TI  - Evidence of effectiveness of herbal medicinal products in the treatment of
      arthritis. Part I: Osteoarthritis.
AB  - Herbal medicinal products (HMPs) are used in a variety of oral and topical forms
      for the treatment of osteoarthritis. The aim of this study was to update a
      previous systematic review published in 2000. We searched electronic databases
      (MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane registers) to June 2007,
      unrestricted by date or language, and included randomized controlled trials that
      compared HMPs with inert (placebo) or active controls in patients with
      osteoarthritis. Five reviewers contributed to data extraction. Disagreements were
      discussed and resolved by consensus with reference to Cochrane guidelines and
      advice from the Cochrane Collaboration.Thirty-five studies (30 studies identified
      for this review update, and 5 studies included in the original review) evaluating
      the effectiveness of 22 HMPs were included. However, due to differing HMPs,
      interventions, comparators, and outcome measures, meta-analysis was restricted to
      data from studies of three HMPs: topical capsaicin, avocado-soybean
      unsaponifiables, and the Chinese herbal mixture SKI306X showed benefit in the
      alleviation of osteoarthritic pain.Several studies investigating products from
      devil's claw, and a powder from rose hip and seed, reported favorable effects on
      osteoarthritic pain, whereas two studies of a willow bark extract returned
      disparate results. Three studies of Phytodolor N(R) were of limited use because
      doses and measures were inconsistent among trials. The remaining single studies
      for each HMP provided moderate evidence of effectiveness. No serious side effects
      were reported with any herbal intervention.Despite some evidence, the
      effectiveness of none of the HMPs is proven beyond doubt. The obvious potential
      benefits of HMPs in the treatment of osteoarthritis are reduced reliance on
      synthetic medications with the associated risks of harmful adverse events, but
      further clinical trials are necessary before HMPs can be adopted in
      osteoarthritis treatment guidelines.

PMID- 19856320
TI  - Managing the risk of insect resistance to transgenic insect control traits:
      practical approaches in local environments.
AB  - BACKGROUND: Growers have enthusiastically embraced crops genetically modified to
      express Bacillus thuringiensis (Bt) proteins for insect control because they
      provide excellent protection from key damaging insect pests around the world. Bt
      crops also offer superior environmental and health benefits while increasing
      grower income. However, insect resistance development is an important concern for
      all stakeholders, including growers, technology providers and seed companies that
      develop these genetically modified crops. Given the marked benefits associated
      with Bt crops, insect resistance management (IRM) must be a consideration when
      cultivating these crops. RESULTS: The technical data and practical experience
      accumulated with Bt crops in many global regions can inform different aspects of
      resistance management leading to robust, science-based IRM plans. A range of
      elements should be considered in assembling any IRM strategy, including: pest
      biology/ecology, product deployment patterns, local cropping systems, insect
      susceptibility monitoring, stakeholder/grower communications, and a remedial
      action plan should resistance develop. Each of these elements is described in
      more detail, with specific examples of how these elements can be combined and
      tailored to the local/regional environments and grower practices. CONCLUSION: IRM
      plans need to be suitable for the given production situation. What works for
      large monoculture production systems in North America is unlikely to be
      appropriate for the small, more diverse agriculture of southeast Asia or Africa.
      Though it is clear that Bt crops impart considerable value to growers, it is also
      clear that it is in the best interest of all stakeholders to preserve Bt proteins
      for the long-term benefits they provide.

PMID- 19856321
TI  - Bayesian methods of analysis for cluster randomized trials with count outcome
      data.
AB  - Bayesian approaches to inference in cluster randomized trials have been
      investigated for normally distributed and binary outcome measures. However,
      relatively little attention has been paid to outcome measures which are counts of
      events. We discuss an extension of previously published Bayesian hierarchical
      models to count data, which usually can be assumed to be distributed according to
      a Poisson distribution. We develop two models, one based on the traditional rate
      ratio, and one based on the rate difference which may often be more intuitively
      interpreted for clinical trials, and is needed for economic evaluation of
      interventions. We examine the relationship between the intracluster correlation
      coefficient (ICC) and the between-cluster variance for each of these two models.
      In practice, this allows one to use the previously published evidence on ICCs to
      derive an informative prior distribution which can then be used to increase the
      precision of the posterior distribution of the ICC. We demonstrate our models
      using a previously published trial assessing the effectiveness of an educational
      intervention and a prior distribution previously derived. We assess the
      robustness of the posterior distribution for effectiveness to departures from a
      normal distribution of the random effects.

PMID- 19856322
TI  - Preferred drifting along the DNA major groove and cooperative anchoring of the
      p53 core domain: mechanisms and scenarios.
AB  - While the importance of specific p53-DNA binding is broadly accepted, the
      recognition process is still not fully understood. Figuring out the initial
      tetrameric p53-DNA association and the swift and cooperative search for specific
      binding sites is crucial for understanding the transactivation mechanism and
      selectivity. To gain insight into the p53-DNA binding process, here we have
      carried out explicit solvent molecular dynamic (MD) simulations of several p53
      core domain-DNA conformations with the p53 and the DNA separated by varying
      distances. p53 approached the DNA, bound non-specifically, and quickly drifted
      along the DNA surface to find the major groove, cooperatively anchoring in a way
      similar to the specific binding observed in the crystal structure. Electrostatics
      was the major driving force behind the p53 movement. Mechanistically, this is a
      cooperative process: key residues, particularly Lys120 and Arg280 acted as
      sensors; upon finding their hydrogen-bonding partners, they lock in, anchoring
      p53 into the major groove. Concomitantly, the DNA adopted a conformation that
      facilitated p53 easy access. The initial non-specific core domain-DNA contacts
      assist in shifting the DNA and the p53 substrates toward conformations "ready"
      for specific major groove binding, with subsequent optimization of the
      interactions. This work is an invited contribution for the special issue of the
      Journal of Molecular Recognition dedicated to Professor Martin Karplus.

PMID- 19856323
TI  - Probing the interaction between recombinant human myelin basic protein and
      caseins using surface plasmon resonance and diffusing wave spectroscopy.
AB  - An intrinsically unstructured human myelin basic protein (hMBP) was expressed in
      the milk of transgenic cows (TGmilk) and found exclusively associated with the
      casein micellar phase. The interaction between the recombinant protein and milk
      caseins was investigated using surface plasmon resonance (SPR). An anti-human
      myelin basic protein antibody was covalently immobilized to the surface of the
      sensor chip. Subsequently the interaction between the recombinant protein
      (captured by this antibody) and caseins was studied in comparison to that noted
      with its human counterpart. Results showed a calcium-mediated interaction between
      the recombinant protein and caseins. The order of magnitude of this interaction
      was in agreement with the number of phosphorylated residues carried by each type
      of casein (alpha(s)- > beta- > kappa-casein). This selective interaction was not
      noted between the human protein and milk caseins indicating that the recombinant
      protein was phosphorylated to a higher extent than the human protein. The
      obtained results indicated that the co-expression of the recombinant protein and
      caseins by the mammary gland along with the recombinant protein's ability to form
      calcium bridges played a key role in the association of the recombinant human
      myelin basic protein (rhMBP) with the casein micelles of milk. Despite this
      association between the recombinant protein and milk caseins, light scattering
      investigations using diffusing wave spectroscopy (DWS) showed no significant
      differences between the milks of the transgenic and the non-transgenic control
      cows, with respect to both the average micelle size and surface charges. This was
      attributed to the low expression levels of the recombinant protein in milk.

PMID- 19856324
TI  - Estimating average annual per cent change in trend analysis.
AB  - Trends in incidence or mortality rates over a specified time interval are usually
      described by the conventional annual per cent change (cAPC), under the assumption
      of a constant rate of change. When this assumption does not hold over the entire
      time interval, the trend may be characterized using the annual per cent changes
      from segmented analysis (sAPCs). This approach assumes that the change in rates
      is constant over each time partition defined by the transition points, but varies
      among different time partitions. Different groups (e.g. racial subgroups),
      however, may have different transition points and thus different time partitions
      over which they have constant rates of change, making comparison of sAPCs
      problematic across groups over a common time interval of interest (e.g. the past
      10 years). We propose a new measure, the average annual per cent change (AAPC),
      which uses sAPCs to summarize and compare trends for a specific time period. The
      advantage of the proposed AAPC is that it takes into account the trend
      transitions, whereas cAPC does not and can lead to erroneous conclusions. In
      addition, when the trend is constant over the entire time interval of interest,
      the AAPC has the advantage of reducing to both cAPC and sAPC. Moreover, because
      the estimated AAPC is based on the segmented analysis over the entire data
      series, any selected subinterval within a single time partition will yield the
      same AAPC estimate--that is it will be equal to the estimated sAPC for that time
      partition. The cAPC, however, is re-estimated using data only from that selected
      subinterval; thus, its estimate may be sensitive to the subinterval selected. The
      AAPC estimation has been incorporated into the segmented regression (free)
      software Joinpoint, which is used by many registries throughout the world for
      characterizing trends in cancer rates.

PMID- 19856325
TI  - Using two-photon excitation to control bending motions in molecular-crystal
      nanorods.
AB  - Molecular-crystal nanorods composed of 9-anthracenecarboxylic acid can undergo
      reversible bending due to molecular-level geometry changes associated with the
      photodimerization of the molecules in the crystal lattice. The use of highly
      focused near-IR femtosecond laser pulses results in two-photon excitation of
      micrometer-scale regions and is used to induce transient bends at various
      locations along the length of a single 200-nm-diameter nanorod. Bending can be
      observed in nanorods with diameters as small as 35 nm, and translational motion
      of a single nanorod could be induced by sequential bending of longer segments. A
      kinetic model is presented that quantitatively describes the bending and
      relaxation dynamics of individual rods. The results of this work show that it is
      possible to use laser excitation conditions to control the location, rate, and
      magnitude of photodeformations in these nanorods. The ability to control the
      motion of these ultrasmall photomechanical structures may be useful for
      manipulating objects on the nanoscale.

PMID- 19856328
TI  - Field-induced nanolithography for high-throughput pattern transfer.

PMID- 19856326
TI  - Biofunctionalized, phosphonate-grafted, ultrasmall iron oxide nanoparticles for
      combined targeted cancer therapy and multimodal imaging.
AB  - A novel, inexpensive biofunctionalization approach is adopted to develop a
      multimodal and theranostic nanoagent, which combines cancer-targeted magnetic
      resonance/optical imaging and pH-sensitive drug release into one system. This
      multifunctional nanosystem, based on an ultrasmall superparamagnetic iron oxide
      (USPIO) nanocore, is modified with a hydrophilic, biocompatible, and
      biodegradable coating of N-phosphonomethyl iminodiacetic acid (PMIDA). Using
      appropriate spacers, functional molecules, such as rhodamine B isothiocyanate,
      folic acid, and methotrexate, are coupled to the amine-derivatized USPIO-PMIDA
      support with the aim of endowing simultaneous targeting, imaging, and
      intracellular drug-delivering capability. For the first time, phosphonic acid
      chemistry is successfully exploited to develop a stealth, multifunctional
      nanoprobe that can selectively target, detect, and kill cancer cells
      overexpressing the folate receptor, while allowing real-time monitoring of tumor
      response to drug treatment through dual-modal fluorescence and magnetic resonance
      imaging.

PMID- 19856327
TI  - Bright photoluminescence from the inner tubes of "peapod"-derived double-walled
      carbon nanotubes.

PMID- 19856329
TI  - Dimensions of the fetal facial profile in normal pregnancy.
AB  - OBJECTIVE: To determine sonographic dimensions of the fetal facial profile in
      normal pregnancy. METHODS: This was a prospective, cross-sectional study of 397
      normal healthy fetuses at 14-33 weeks of gestation. After exclusion of the small
      numbers of patients at the upper GAs, 379 patients between 14.0 and 26.9 weeks of
      gestation were included in the analyses. The sagittal plane of the fetal facial
      profile was evaluated using transvaginal and transabdominal ultrasound. Distances
      from the tip of the nose to the mouth (the line between the lips), from the mouth
      to the gnathion (lower chin), from the upper philtrum to the mouth, and from the
      mouth to the upper concavity of the chin were measured and are presented
      according to gestational age (GA). RESULTS: There was a significant linear
      correlation between GA and the distance from the tip of the nose to the mouth (r
      = 0.943; P < 0.00001; y = -37.98 + 7.54 x GA), from the mouth to the gnathion (r
      = 0.946; P < 0.00001; y = -46.34 + 7.95 x GA), from the upper level of the
      philtrum to the mouth (r = 0.71; P < 0.00001; y = 0.22 + 3.33 x GA) and from the
      mouth to the upper concavity of the chin (r = 0.665; P < 0.00001; y = 1.65 + 2.95
      x GA). The ratio between the distance from the tip of the nose to the mouth and
      that from the mouth to the gnathion was also almost constant throughout
      gestation, as was the ratio between the distance from the upper philtrum to the
      mouth and that from the mouth to the upper concavity of the chin. CONCLUSIONS: We
      provide normative data of the fetal facial profile across GA. Our data offer a
      potential tool for the prenatal diagnosis of abnormal fetal facial profile.

PMID- 19856330
TI  - Synthesis and evaluation on anticonvulsant and antidepressant activities of 5
      Alkoxy-tetrazolo[1,5-a]quinazolines.
AB  - Several 5-alkoxy-tetrazolo[1,5-a]quinazoline derivatives have been synthesized by
      reacting 2,4-dichloroquinazoline with various phenols or aliphatic alcohol and
      then with sodium azide. The structures of these compounds have been confirmed by
      IR, MS,( 1)H-NMR, and elementary analysis. Anticonvulsant activities were
      evaluated using the maximal electroshock (MES) test. Most of the synthesized
      compounds displayed weak anticonvulsant activity at a dose of 300 mg/kg.
      Antidepressant activities were investigated by forced swimming test. Two
      compounds, namely 5-(hexyloxy)tetrazolo[1,5-a]quinazoline and 5-(4
      methoxyphenoxy)tetrazolo[1,5-a]quinazoline, showed significant antidepressant
      activity, which decreased the immobility time by 62.2 and 51.7% at 100 mg/kg dose
      level.

PMID- 19856331
TI  - Proline analogue of nitrosourea as a new cytotoxic prodrug.
AB  - Carmustine is frequently used as anticancer drug. High toxicity and low
      selectivity reduces the application of this drug. Though, there is a necessity to
      find new compounds characterized by similar therapeutic effects but a higher
      selectivity and safety. As a result, the proline analogue of nitrosourea, N-[N'
      (2-bromophenyl)-N'-nitrosocarbamoyl]proline (AC), has been synthesized. The aim
      of this study was to compare the influence of carmustine and the proline analogue
      of nitrosourea on the antioxidant abilities of fibroblasts and leukemia cells,
      MOLT4. It was shown that carmustine as well as AC cause an increase in hydrogen
      peroxide concentration in normal and neoplastic cells. Incubation with both
      compounds led to a diminution of the activity of antioxidant enzymes such as
      superoxide dismutase, glutathione peroxidase, and reductase. Changes in activity
      / level of antioxidant parameters were accompanied by augmentation of lipid and
      oxidative protein modifications. In conclusion, carmustine and AC cause changes
      in the antioxidative system of normal and MOLT4 cells and are a reason of
      oxidative stress formation.

PMID- 19856332
TI  - Synthesis of novel uracil non-nucleoside derivatives as potential reverse
      transcriptase inhibitors of HIV-1.
AB  - Novel emivirine and TNK-651 analogues 5a-d were synthesized by reaction of
      chloromethyl ethyl ether and / or benzyl chloromethyl ether, respectively, with
      uracils having 5-ethyl and 6-(4-methylbenzyl) or 6-(3,4-dimethoxybenzyl)
      substituents. A series of new uracil non-nucleosides substituted at N-1 with
      cyclopropylmethyloxymethyl 9a-d, 2-phenylethyloxymethyl 9e-h, and 3-phenylprop-1
      yloxymethyl 9i-l were prepared on treatment of the corresponding uracils with the
      appropriate acetals 8a-c. Some of the tested compounds showed good activity
      against HIV-1 wild type. Among them, 1-cyclopropylmethyloxymethyl-5-ethyl-6-(3,5
      dimethylbenzyl)uracil 9c and 5-ethyl-6-(3,5-dimethylbenzyl)-1-(2
      phenylethyloxymethyl)uracil 9g showed inhibitory potency equally to emivirine
      against HIV-1 wild type. Furthermore, compounds 9c and 9g showed marginal better
      activity against NNRTI resistant mutants than emivirine.

PMID- 19856333
TI  - Synthesis of 2-fluoro N(10)-substituted acridones and their cytotoxicity studies
      in sensitive and resistant cancer cell lines and their DNA intercalation studies.
AB  - A series of 2-fluoro N(10)-substituted acridone derivatives with varying alkyl
      side chain length with propyl, butyl substitution, and a tertiary amine group at
      the terminal end of the alkyl side chain were synthesized and screened against
      cancer cell lines SW 1573, SW 1573 2R 160 (P-gp substrate) which are non-small
      lung cancer cell lines, MCF-7, MCF-7/MR (BCRP substrate) are breast cancer cell
      lines, 2008 WT, 2008MRP1, 2008MRP2, 2008MRP3 are ovarian cancer cell lines, and
      human embryo kidney cell lines like HEK293, HEK293 MRP4, and HEK293 MRP5i. The
      propyl-series compounds showed lipophilicity in the range of 1.93 to 4.40 and the
      butyl series in the range of 2.37 to 4.78. The compounds 4, 7, and 8 showed good
      cytotoxicity against the 60 human cancer cell line panel of the National Cancer
      Institute, USA. The compounds 14 and 15 showed a better cytotoxicity in most of
      the cancer cell lines compared to other compounds tested. The DNA-binding
      properties of the compounds were evaluated based on their affinity or
      intercalation with CT-DNA measured with absorption titration. The compound 11
      bearing planar tricyclic ring linked with a butyl methylpiperazino side chain
      showed the highest binding affinity with a binding constant (K(i)) of 10.38 x 10
      M(-1). Evaluation of the compounds in cell lines with an overexpression of
      various multidrug resistance-related protein (MRP), P-glycoprotein (P-gp), or
      Breast Cancer Resistance Protein (BCRP) showed that all compounds are not
      substrates for any of these transporters.

PMID- 19856339
TI  - Chemical shift calibration of 1H MAS NMR liver tissue spectra exemplified using a
      study of glycine protection of galactosamine toxicity.
AB  - High-resolution (1)H magic angle spinning (MAS) NMR spectroscopy is a useful tool
      for analysing intact tissues as a component of metabonomic studies. The effect of
      referencing MAS NMR spectra to the chemical shifts of glucose or to that or
      trimethylsilylpropionic acid on the resultant multivariate statistical models
      have been investigated. It is shown that referencing to known chemical shifts of
      either alpha-glucose or beta-glucose in (1)H MAS NMR-based metabolic data of
      intact liver tissues is preferred. This has been exemplified in studies of
      galactosamine toxicity in the rat where co-administration of glycine ameliorates
      the toxic response. This approach leads to better aligned sets of spectra and
      reduces the inter-sample variability in multivariate statistical models. If
      glucose is not present in the tissue under study, then a number of alternative
      internal reference chemical shifts are presented. Finally, the chemical shift
      difference between that of the anomeric H1 proton of alpha-glucose and residual
      water is confirmed as a suitable internal temperature calibration method.

PMID- 19856340
TI  - Fifty years of the integrated control concept: the role of landscape ecology in
      IPM in San Joaquin valley cotton.
AB  - In defining the integrated control concept, Stern, Smith, van den Bosch and Hagan
      described 'understanding the ecosystem' as a key underpinning of the concept. In
      following years, Stern and van den Bosch continued to refine and expand the role
      of the ecological landscape. They and their colleagues developed cultural
      practices that took advantage of this understanding to limit the need of
      pesticide intervention in cotton in the San Joaquin Valley during the 1960s and
      1970s. Research and extension activities in the intervening years built upon
      those fundamental concepts using geospatial tools and analytical techniques to
      refine current understanding and develop ecological landscape level approaches to
      manage Lygus hesperus (Knight) in San Joaquin Valley cotton, Gossypium hirsutum
      (L.) and more recently G. barbadense (L.). The result has been a significant drop
      in insecticide use against L. hesperus, with less than one application per season
      during the 1990 s and early 2000s.

PMID- 19856341
TI  - Poly(L-lysine)-induced aggregation of single-strand oligo-DNA-modified gold
      nanoparticles.
AB  - Single-strand oligo-DNA-modified Au nanoparticles (AuNPs) undergo aggregation in
      the presence of poly(L-lysine) (PLL), which is attributed to the interactions
      between the oligo-DNA and PLL. These interactions between the oligo-DNA and PLL
      were identified to be electrostatic when the lysine residues of PLL were
      positively charged and to be hydrogen bonding when the residues were
      deprotonated. The aggregation was promoted with an increase in the pH value at a
      pH level lower than the pK(a) value of PLL (pK(a) approximately 10.0) due to the
      gradual deprotonation of the lysine residues and thus suppressed electrostatic
      interactions between the positively charged lysine residues of PLL and the
      negatively charged backbone phosphate groups of the oligo-DNA. At pH levels
      higher than the pK(a) value of PLL, the aggregation was identified to be
      dominated by the hydrogen bonds between the bases of the oligo-DNA and the
      deprotonated lysine residues of PLL. This study prompts the possibility that the
      spectral, and thus color, change of AuNPs upon aggregation can be used as a probe
      to follow the interactions between oligo-DNA and polypeptides.

PMID- 19856342
TI  - Molecular double-bond covalent radii for elements Li-E112.
AB  - The previous systems of triple-bond and single-bond self-consistent, additive
      covalent radii, R(AB)=r(A)+ r(B), are completed with a fit for sigma(2)pi(2)
      double-bonds.The primary bond lengths, R, are taken from experimental or
      theoretical data corresponding to chosen group valencies. All r(E) values are
      obtained from the same, self-consistent fit. Many of the calculated primary data
      came from E=CH(2) and H-E=CH(2) models. Homonuclear LE=EL, formaldehyde-type
      Group 14-Group 16 and open-shell, X (3) Sigma Group-16 dimer data are included.
      The standard deviation for the 316 included data points is 3 pm.

PMID- 19856343
TI  - Direct ortho-arylation of N-phenacylpyridinium bromide by palladium-catalyzed C-H
      bond activation.
AB  - A novel palladium catalyzed direct ortho-arylation of N-phenacylpyridinium
      bromide was developed. The amazing N-phenacyl group regioselectively activates
      the C-H bond of pyridine and automatically departs from the arylated products. A
      kinetic isotope effect study proved that the reaction went through a C-H-bond
      activation pathway and 2,6-diphenylpyridine was produced stepwise from 2
      phenylpyridine.

PMID- 19856344
TI  - Microwave-promoted palladium(II)-catalyzed C-P bond formation by using
      arylboronic acids or aryltrifluoroborates.
AB  - The first Pd(II)-catalyzed P arylation has been performed by using palladium
      acetate, the rigid bidentate ligand dmphen (dmphen=2,9-dimethyl-1,10
      phenanthroline), and without the addition of base or acid. Couplings of
      arylboronic acids or aryl trifluoroborates with H-phosphonate dialkyl esters were
      conducted in 30 min with controlled microwave (MW) heating under non-inert
      conditions. Aryl phosphites were also synthesized at room temperature with
      atmospheric air as the sole reoxidant. The arylated phosphonates were isolated in
      44-90 % yields. The excellent chemoselectivity of the method was illustrated in
      the synthesis of a Mycobacterium tuberculosis glutamine synthetase (MTB-GS)
      inhibitor. Online ESIMS was used to detect cationic palladium species in ongoing
      reactions directly, and a catalytic cycle has been proposed based on these
      results.

PMID- 19856346
TI  - Ir(III) and Ru(II) complexes containing triazole-pyridine ligands: luminescence
      enhancement upon substitution with beta-cyclodextrin.
AB  - Novel 2-(1-substituted-1H-1,2,3-triazol-4-yl)pyridine (pytl) ligands have been
      prepared by "click chemistry" and used in the preparation of heteroleptic
      complexes of Ru and Ir with bipyridine (bpy) and phenylpyridine (ppy) ligands,
      respectively, resulting in [Ru(bpy)(2)(pytl-R)]Cl(2) and [Ir(ppy)(2)(pytl-R)]Cl
      (R=methyl, adamantane (ada), beta-cyclodextrin (betaCD)). The two
      diastereoisomers of the Ir complex with the appended beta-cyclodextrin,
      [Ir(ppy)(2)(pytl-betaCD)]Cl, were separated. The [Ru(bpy)(2)(pytl-R)]Cl(2) (R=Me,
      ada or betaCD) complexes have lower lifetimes and quantum yields than other
      polypyridine complexes. In contrast, the cyclometalated Ir complexes display
      rather long lifetimes and very high emission quantum yields. The emission quantum
      yield and lifetime (Phi=0.23, tau=1000 ns) of [Ir(ppy)(2)(pytl-ada)]Cl are
      surprisingly enhanced in [Ir(ppy)(2)(pytl-betaCD)]Cl (Phi=0.54, tau=2800 ns).
      This behavior is unprecedented for a metal complex and is most likely due to its
      increased rigidity and protection from water molecules as well as from dioxygen
      quenching, because of the hydrophobic cavity of the betaCD covalently attached to
      pytl. The emissive excited state is localized on these cyclometalating ligands,
      as underlined by the shift to the blue (450 nm) upon substitution with two
      electron-withdrawing fluorine substituents on the phenyl unit. The significant
      differences between the quantum yields of the two separate diastereoisomers of
      [Ir(ppy)(2)(pytl-betaCD)]Cl (0.49 vs. 0.70) are attributed to different
      interactions of the chiral cyclodextrin substituent with the Delta and Lambda
      isomers of the metal complex.

PMID- 19856348
TI  - Fixing the chirality and trapping the transition state of helicene with atomic
      metal glue.
AB  - By combining the intriguing geometrical properties of two classes of well
      established molecules, the metallocenes and the helicenes, we propose a hybrid
      class of structures-the metallohelicenes. In these, the outer most aryl groups of
      a specific helicene are glued together by a complexing metal atom. This
      effectively fixes the chirality of the parent helicene, which otherwise easily
      undergoes thermal racemization. The fixed chirality suggests several interesting
      applications, ranging from building blocks of stable molecules with high circular
      dichroism and optical activity to chiral ligands and catalysts. Alternatively,
      the metal glue can trap the non-chiral transition state structure of helicene.
      High-level quantum chemical calculations show the readiness of formation and
      stability of the proposed complexes.

PMID- 19856349
TI  - Microsolvated and chelated butylzinc cations: formation, relative stability, and
      unimolecular gas-phase chemistry.
AB  - Solutions of butylzinc iodide in tetrahydrofuran, acetonitrile, and N,N
      dimethylformamide were analyzed by electrospray ionization mass spectrometry. In
      all cases, microsolvated butylzinc cations [ZnBu(solvent)(n)](+), n=1-3, were
      detected. The parallel observation of the butylzincate anion [ZnBuI(2)](-)
      suggests that these ions result from disproportionation of neutral butylzinc
      iodide in solution. In the presence of simple bidentate ligands (1,2
      dimethoxyethane, N,N-dimethyl-2-methoxyethylamine, and N,N,N',N'
      tetramethylethylenediamine), chelate complexes of the type [ZnBu(ligand)](+) form
      quite readily. The relative stabilities of these complexes were probed by
      competition experiments and analysis of their unimolecular gas-phase reactivity.
      Fragmentation of mass-selected [ZnBu(ligand)](+) leads to the elimination of
      butene and formation of [ZnH(ligand)](+). In marked contrast, the microsolvated
      cations [ZnBu(solvent)(n)](+) lose the attached solvent molecules upon gas-phase
      fragmentation to produce bare [ZnBu](+), which subsequently dissociates into
      [C(4)H(9)](+) and Zn. This difference in reactivity resembles the situation in
      organozinc solution chemistry, in which chelating ligands are needed to activate
      dialkylzinc compounds for the nucleophilic addition to aldehydes.

PMID- 19856351
TI  - On the synthesis and chemical behaviour of the elusive bis(hydrosulfido)-bridged
      dinuclear rhodium(I) complexes [{Rh(mu-SH)(CO)(PR(3))}(2)].
AB  - Several bis(hydrosulfido)-bridged dinuclear rhodium(I) compounds, [{Rh(mu
      SH)(L)(2)}(2)], have been prepared from rhodium(I) acetylacetonato complexes,
      [Rh(acac)(L)(2)], and H(2)S(g). Reaction of [Rh(acac){P(OPh)(3)}(2)] with
      H(2)S(g) affords the dinuclear bis(hydrosulfido)-bridged compound [{Rh(mu
      SH){P(OPh)(3)}(2)}(2)] (1). However, reaction of complexes [Rh(acac)(CO)(PR(3))]
      with H(2)S(g) gives the dinuclear compound [{Rh(mu-SH)(CO)(PR(3))}(2)] (R=Cy, 2;
      R=Ph, 4) and the trinuclear cluster [Rh(3)(mu-H)(mu(3)-S)(2)(CO)(3)(PR(3))(3)]
      (R=Cy, 3; R=Ph, 5). The selective synthesis of both type of compounds has been
      carried out by control of the H(2)S(g) concentration in the reaction media. The
      trinuclear hydrido-sulfido cluster [Rh(3)(mu-H)(mu(3)-S)(2)(CO)(3)(PPh(3))(3)]
      (5) has been also obtained by reaction of [{Rh(mu-SH)(CO)(PPh(3))}(2)] (4) with
      [Rh(acac)(CO)(PPh(3))], proceeding through the trinuclear hydrosulfido-sulfido
      intermediate [Rh(3)(mu(3)-SH)(mu(3)-S)(CO)(3)(PPh(3))(3)]. The molecular
      structures of complexes 1 and 3 have been determined by X-ray diffraction
      methods. Compound 1 is stable in solution, but complexes 2 and 4 slowly transform
      in solution into the trinuclear hydrido-sulfido clusters 3 and 5, respectively,
      with the release of H(2)S(g) in a reversible way. (1)H NMR kinetic experiments
      for the transformation of 4 into 5 have revealed that this transformation follows
      second-order-type kinetic. The following activation parameters, DeltaH( not
      equal)=24+/-3 kJ mol(-1) and of DeltaS( not equal)=-223+/-8 J K(-1) mol(-1), have
      been calculated from the determination of the second-order rate constants in the
      temperature range 30-45 degrees C. The large negative value of the activation
      entropy is consistent with an associative character of the rate-determining step.
      A plausible multistep mechanism based on the chemical behaviour of hydrosulfido
      metal complexes and compatible with the kinetic behaviour has been proposed.

PMID- 19856352
TI  - Rhodium/N-heterocyclic carbene catalyzed direct intermolecular arylation of sp2
      and sp3 C-H bonds with chelation assistance.

PMID- 19856353
TI  - Liposomes by polymerization of an imidazolium ionic liquid: use as microreactors
      for gold-catalyzed alcohol oxidation.
AB  - The bipodal ionic liquid N,N'-bis(10-undecenyl)-2-methylimidazolium underwent
      polymerization in aqueous media with potassium persulfate to form submicrometric
      liposomes. A TEM study indicated that the liposomes are the result of several
      morphological transformations of the polymer particles. Photopolymerization at
      room temperature led to spherical particles with some internal voids and polymer
      chains. We took advantage of the positive charge on the imidazolium rings and
      used a photocuring agent to form in a single step starting from the imidazolium
      monomer and NaAuCl(4) spherical polymer particles containing gold nanoparticles
      (10-15 nm) in their interior. This system was found to promote the selective
      aerobic oxidation of 2-hydroxybenzyl alcohol to salicylaldehyde.

PMID- 19856354
TI  - Nucleic acid bases in the gas phase.

PMID- 19856355
TI  - Biomimetic encapsulation of individual cells with silica.

PMID- 19856356
TI  - Reusable catalysts based on dendrimers trapped in poly(p-xylylene) nanotubes.

PMID- 19856357
TI  - Synthesis of tin dioxide octahedral nanoparticles with exposed high-energy {221}
      facets and enhanced gas-sensing properties.

PMID- 19856358
TI  - Silver-mediated direct amination of benzoxazoles: tuning the amino group source
      from formamides to parent amines.

PMID- 19856359
TI  - Evolution of amber suppressor tRNAs for efficient bacterial production of
      proteins containing nonnatural amino acids.

PMID- 19856360
TI  - Phenylthiomethyl glycosides: convenient synthons for the formation of azidomethyl
      and glycosylmethyl glycosides and their derivatives.

PMID- 19856361
TI  - Oxidative addition of halogens on open metal sites in a microporous spin
      crossover coordination polymer.

PMID- 19856362
TI  - BTB-1: a small molecule inhibitor of the mitotic motor protein Kif18A.

PMID- 19856363
TI  - Isolation and structural characterization of the molecular nanocapsule
      Sm(2)@D(3d)(822)-C(104).

PMID- 19856365
TI  - Inhibition of HSP90 with pochoximes: SAR and structure-based insights.
AB  - The pochoximes, based on the radicicol pharmacophore, are potent inhibitors of
      heat shock protein 90 (HSP90) that retain their activity in vivo. Herein we
      report an extended library that broadly explores the structure-activity
      relationship (SAR) of the pochoximes with four points of diversity. Several
      modifications were identified that afford improved cellular efficacy, new
      opportunities for conjugation, and further diversifications. Cocrystal structures
      of pochoximes A and B with HSP90 show that pochoximes bind to a different
      conformation of HSP90 than radicicol and provide a rationale for the enhanced
      affinity of the pochoximes relative to radicicol and the pochonins.

PMID- 19856366
TI  - 4-exo cyclizations by template catalysis.

PMID- 19856368
TI  - Optical, mechanical, and opto-mechanical switching of anchored dithioazobenzene
      bridges.

PMID- 19856367
TI  - A minimalist substrate for enzymatic peptide and protein conjugation.
AB  - Recently a number of nonnatural prenyl groups containing alkynes and azides have
      been developed as handles to perform click chemistry on proteins and peptides
      ending in the sequence "CAAX", where C is a cysteine that becomes alkylated, A is
      an aliphatic amino acid and X is any amino acid. When such molecules are
      modified, a tag containing a prenyl analogue and the "CAAX box" sequence remains.
      Here we report the synthesis of an alkyne-containing substrate comprised of only
      nine nonhydrogen atoms. This substrate was synthesized in six steps from 3
      methylbut-2-en-1-ol and has been enzymatically incorporated into both proteins
      and peptides by using protein farnesyltransferase. After prenylation the final
      three amino acids required for enzymatic recognition can be removed by using
      carboxypeptidase Y, leaving a single residue (the cysteine from the "CAAX box")
      and the prenyl analogue as the only modifications. We also demonstrate that this
      small tag minimizes the impact of the modification on the solubility of the
      targeted protein. Hence, this new approach should be useful for applications in
      which the presence of a large tag hinders the modified protein's solubility,
      reactivity, or utility.

PMID- 19856369
TI  - Synthesis, conjugation, and immunological evaluation of the serogroup 6
      pneumococcal oligosaccharides.
AB  - The first synthesis of the newly discovered oligosaccharide of pneumococcal
      serotype 6C and its spacer-containing analogue is reported. Conjugation of the
      spacer-containing oligosaccharides of pneumococcal saccharides 6A, 6B, 6C and
      derivatives thereof with bovine serum albumin (BSA) protein carrier was carried
      out by using squaric-acid approach to obtain the oligosaccharide-protein
      conjugates in excellent yields. The conjugates have been tested with a rabbit
      antiserum pool (Pool B) used for pneumococcal serotyping. The results showed that
      synthetic carbohydrate conjugates express epitopes found in native capsular
      polysaccharides of serotypes 6A, 6B, and 6C.

PMID- 19856370
TI  - Elucidating protein binding mechanisms by variable-c ITC.

PMID- 19856371
TI  - A high molecular weight donor for electron injection interlayers on metal
      electrodes.
AB  - The molecular donor 9,9'-ethane-1,2-diylidene-bis(N-methyl-9,10-dihydroacridine)
      (NMA) has been synthesized, and its electronic properties were characterized both
      in solution using cyclic voltammetry and optical absorption spectroscopy, and at
      interfaces to metals with photoelectron spectroscopy (PES). The optical energy
      gap of NMA in solution increases by 0.10 eV when the compound is doubly oxidized.
      On the basis of quantum-chemical calculations, this ipsochromic effect is
      rationalized by a change in geometry involving a severe torsion of the two
      acridinium moieties with respect to the central double bond, thus reducing
      conjugation upon oxidation. PES is reported for NMA deposited on Au(111),
      Ag(111), and Cu(111) single crystals. A decrease of the sample work function is
      observed that becomes larger with increasing molecular coverage and clearly
      exceeds values that would be expected for metal surface electron "push back"
      alone, confirming the electron donating nature of NMA. The growth mode of NMA on
      all three surfaces is almost layer-by-layer (Frank-van der Merwe). For tris(8
      hydroxyquinoline)aluminum (Alq(3)) deposited on top of a NMA-modified Au(111)
      surface, the electron injection barrier (EIB) is reduced by 0.25 eV compared to
      that on pristine Au(111). Furthermore, the EIB reduction depends linearly on Phi
      of the donor-modified Au(111) surface, adjustable by NMA precoverage. This
      enables continuous tuning of the EIB in organic electronic devices, in order to
      optimize device efficiency and performance.

PMID- 19856372
TI  - X-ray diffraction as a local probe tool.
AB  - For the structural characterization of nanoscale objects, X-ray diffraction is
      widely used as a technique complementing local probe analysis methods such as
      scanning electron microscopy and transmission electron microscopy. Details on
      strain distributions, chemical composition, or size and shape of nanostructures
      are addressed. X-ray diffraction traditionally obtains very good statistically
      averaged properties over large ensembles-provided this averaging is meaningful
      for ensembles with sufficiently small dispersion of properties. In many cases,
      however, it is desirable to combine different analysis techniques on exactly the
      same nano-object, for example, to gain a more detailed insight into the
      interdependence of properties. X-ray beams focused to diameters in the sub-micron
      range, which are available at third-generation synchrotron sources, allow for
      such X-ray diffraction studies of individual nano-objects.

PMID- 19856373
TI  - Size-dependence of catalytic activity of gold nanoparticles loaded on titanium
      (IV) dioxide for hydrogen peroxide decomposition.

PMID- 19856375
TI  - Active metal electrode-oxide interface in gas sensor operation probed by in situ
      and time-resolved X-ray spectroscopy.

PMID- 19856374
TI  - Anomalous preservation of CH4 hydrate and its dependence on the morphology of
      hexagonal ice.

PMID- 19856376
TI  - Electrically programmable nematofluidics with a high level of selectivity in a
      hierarchically branched architecture.

PMID- 19856377
TI  - Aryldiketo acids have antibacterial activity against MDR Staphylococcus aureus
      strains: structural insights based on similarity and molecular interaction
      fields.

PMID- 19856378
TI  - 2-substituted-3-dehydroquinic acids as potent competitive inhibitors of type II
      dehydroquinase.

PMID- 19856379
TI  - Oxidation of Rh/Ce(0.5)Zr(0.5)O(2) reduced under mild conditions as an initiator
      of n-butane oxidative reforming at ambient temperature.

PMID- 19856380
TI  - Telomerization of butadiene with starch under mild conditions.
AB  - The design of industrial products based on bioresources is a challenging issue.
      Modification of starch, by hydrophobic chemical substituents, results in an
      innovative hydrophobic material. Herein, the hydrophobic part of the derivative,
      comprised of octadienyl chains, is introduced through catalytic butadiene
      telomerization. The process is efficiently conducted on starch in its granular
      form in an aqueous medium using hydrosoluble palladium complexes. After
      optimization, a turnover number (TON) of up to 550 was achieved in the presence
      of [(pi-allyl)PdCl](2) catalyst and, unusually, by using dimethylisosorbide as a
      cosolvent.

PMID- 19856382
TI  - Fed-batch production of tetanus toxin by Clostridium tetani.
AB  - This study deals with the effects of the initial nitrogen source (NZ Case TT)
      level and the protocol of glucose addition during the fed-batch production of
      tetanus toxin by Clostridium tetani. An increase in the initial concentration of
      NZ Case TT (NZ(0)) accelerated cell growth, increased the consumption of the
      nitrogen source as well as the final yield of tetanus toxin, which achieved the
      highest values (50-60 L(f)/mL) for NZ(0) > or = 50 g/L. The addition of glucose
      at fixed times (16, 56, and 88 h) ensured a toxin yield ( approximately 60
      L(f)/mL) about 33% higher than those of fed-batch runs with addition at fixed
      concentration ( approximately 45 L(f)/mL) and about 300% higher than those
      obtained in reference batch runs nowadays used at industrial scale. The results
      of this work promise to substantially improve the present production of tetanus
      toxin and may be adopted for human vaccine production after detoxification and
      purification.

PMID- 19856383
TI  - History of IPM in California pears--50 years of pesticide use and the transition
      to biologically intensive IPM.
AB  - During the 1960s, the California pear industry, on a per acre basis, was among
      the heaviest users of pesticides. Each season, multiple sprays of up to 14 active
      ingredients (chlorinated hydrocarbons, organophosphates and carbamates) were
      typically applied for control of insects and mites. The cost of control escalated
      while damage from arthropod pests increased owing to greater pest resistance and
      more pest resurgence. The pear industry suffered classic symptoms of the
      'pesticide treadmill'. By the late 1960s, key pear industry leaders demanded
      action. Simultaneously, newly emerging concepts of IPM were being developed and
      funded. With public awareness and environmental activism on the rise in the wake
      of Rachel Carson's Silent Spring, the stage was set for change. This paper
      elucidates how pear growers, university researchers and extension agents,
      environmentalists, government regulators, private consultants, farm chemical
      suppliers and others contributed to the reduction in insecticide use in
      California pear orchards. Today, arthropod IPM in pears is characterized as
      relatively low input, biologically intensive and very successful. For example, in
      2008 many pear growers only applied between three and five active ingredients
      (mainly organically certified) per season for control of arthropods.

PMID- 19856384
TI  - Simultaneous measurement of N-H and Calpha-Halpha coupling constants in proteins.
AB  - We present a pulse sequence for the simultaneous measurement of N-H and Calpha
      Halpha couplings in double-labeled proteins from 2D spectra. The proposed
      sequence, a modification of the HN(CO)CA experiment, combines the J-modulation
      method and the IPAP scheme. The couplings can be readily retrieved from a series
      of 2D (15)N-(1)H correlation spectra, differing in the time point at which a (1)H
      180 degrees pulse is applied. This induces an intensity modulation of the (15)N
      (1)H correlation peaks with the Calpha-Halpha coupling. The Calpha-Halpha
      coupling is then obtained by fitting the observed intensities to the modulation
      equation. The N-H coupling is measured in each member of the set from peak-to
      peak separations in the IPAP subspectra. The pulse sequence is experimentally
      verified with a sample of (15)N/(13)C-enriched ubiquitin.

PMID- 19856385
TI  - Monitoring the fractionation of a whey protein isolate during dead-end membrane
      filtration using fluorescence and chemometric methods.
AB  - During membrane-based separation of proteins, changes in protein concentration of
      the permeate and retentate streams occurs over time. The current work proposes a
      new approach for monitoring the changes in concentrations of proteins in both
      permeate and retentate by making use of data collected using fluorescence
      spectroscopy and intrinsic protein fluorescence analyzed by multivariate
      statistical techniques. Whey protein isolate consists mainly of alpha-lactalbumin
      (alpha-LA), beta-lactoglobulin (beta-LG), and small proportion of bovine serum
      albumin (BSA) and was used as a model system in this study. A fiber optic probe
      (FOP) was used to acquire multiwavelength fluorescence spectra for permeate and
      retentate streams at different times during UF-based separation of the components
      from a multicomponent solution. Multivariate regression models were developed for
      predicting the concentrations of alpha-LA, beta-LG, and BSA by establishing a
      calibration model between data acquired using the FOP and the corresponding
      protein concentration levels measured by size-exclusion chromatography. The model
      was validated using FOP data that were not previously used for calibration of the
      regression models. This comparison showed that concentrations of alpha-LA, beta
      LG, and BSA could be predicted directly from FOP data within reasonable accuracy
      by making use of multivariate calibration tools. This approach has several
      attractive features including that it is nondestructive, fast, and relatively
      simple to perform. This technique has potential practical applications as it
      could offer the opportunity for in situ monitoring of membrane filtration
      processes by tracking individual protein transmission and selectivity of
      fractionation.

PMID- 19856386
TI  - The development of the birdcage resonator: a historical perspective.
AB  - The author gives a personal account of the development of the birdcage resonator
      while he worked at GE Medical Systems. The emphasis is on promoting an intuitive
      understanding of the underlying principles of RF coil design by recounting the
      assumptions, misconceptions, and reasoning involved in addressing the challenging
      problems in a new field of technology. Topics covered include the historic
      context of early MRI development, the critical role of RF coil technology in high
      field imaging, the need for an RF shield, the importance of distributed
      capacitance, the scientific controversies over magnetic field strength for
      imaging, a comparison of the birdcage design to an earlier Technicare phased
      coil, the distribution of electric fields in birdcage resonators, and the
      limitations of birdcages at very high fields. The author often cites less well
      known patent literature on RF coil technology.

PMID- 19856387
TI  - Radio frequency coils are the 'lenses' of the MRI system.

PMID- 19856389
TI  - Paediatric presentation of familial cerebral cavernoma.
AB  - We report the case of a 13-year-old male who presented with headaches and was
      presumed to have a brain tumour. He was subsequently found to have multiple
      cerebral cavernomas with haemorrhage and positive family history. We review the
      literature on familial cavernomas. Cerebral cavernous malformations (CCMs) are
      characterized by abnormally enlarged capillary cavities without intervening brain
      parenchyma [Verlaan et al. Neurology 2005; 65:1982-1983] that may involve any
      part of the central nervous system. Focal neurologic deficit and haemorrhage
      occur in 45% of children, higher than in adults [Stoeter. Neurosurg Rev 2001;
      24]. Paediatric patients with symptomatic cavernous malformations should be
      treated surgically because of the risk of haemorrhage [Lee et al. Child's Nervous
      Syst 2008; 24:321-327].

PMID- 19856388
TI  - Initial testing (stage 1) of mapatumumab (HGS-ETR1) by the pediatric preclinical
      testing program.
AB  - Mapatumumab (HGS-ETR1) is a fully human IgG1 agonistic monoclonal antibody that
      exclusively targets and activates tumor necrosis factor-related apoptosis
      inducing ligand receptor 1 (TRAIL-R1). It was tested in vitro at concentrations
      from 0.01 to 100 microg/ml and in vivo at a dose of 10 mg/kg administered
      intraperitoneally using a twice-weekly schedule. Mapatumumab demonstrated limited
      activity against the 23 cell lines of the PPTP in vitro panel with no lines
      achieving 50% growth inhibition. Mapatumumab induced significant differences in
      event-free survival distribution compared to controls in 9 of 37 evaluable solid
      tumor xenografts tested, but in none of the 8 ALL xenografts.

PMID- 19856390
TI  - Carbon nanotube clusters as universal bacterial adsorbents and magnetic
      separation agents.
AB  - The magnetic susceptibility and high bacterial affinity of carbon nanotube (CNT)
      clusters highlight their great potential as a magnetic bio-separation agent. This
      article reports the CNT clusters' capability as "universal" bacterial adsorbents
      and magnetic separation agents by designing and testing a multiwalled carbon
      nanotube (MWNT) cluster-based process for bacterial capturing and separation. The
      reaction system consisted of large clusters of MWNTs for bacterial capture and an
      external magnet for bio-separation. The designed system was tested and optimized
      using Escherichia coli as a model bacterium, and further generalized by testing
      the process with other representative strains of both gram-positive and gram
      negative bacteria. For all strains tested, bacterial adsorption to MWNT clusters
      occurred spontaneously, and the estimated MWNT clusters' adsorption capacities
      were nearly the same regardless of the types of strains. The bacteria-bound MWNT
      clusters also responded almost instantaneously to the magnetic field by a rare
      earth magnet (0.68 Tesla), and completely separated from the bulk aqueous phase
      and retained in the system. The results clearly demonstrate their excellent
      potential as highly effective "universal" bacterial adsorbents for the
      spontaneous adsorption of any types of bacteria to the clusters and as
      paramagnetic complexes for the rapid and highly effective magnetic separations.

PMID- 19856391
TI  - Pitfalls in the differential diagnosis of renal tumor in an adolescent.
AB  - The differential diagnosis of renal tumors, particularly in adolescents, may be
      challenging. We describe an 11-year-old female with a primary intra-renal mass.
      Initial differential diagnoses included primitive neuroectodermal tumor (PNET),
      desmoplastic small round cell tumor (DSRCT), and Wilms Tumor (WT). Extensive
      pathologic and molecular analysis on initial and relapsed tumor samples confirmed
      WT. The EWS-WT1 and EWS-FLI1 rearrangements, distinctive of DSRCT and PNET were
      negative. The differential diagnosis on monophasic blastemal WT may be complex.
      Primary renal DSRCT and PNET have been rarely described. Nevertheless, molecular
      confirmation for these rare conditions may be necessary in selected cases.

PMID- 19856393
TI  - Rapamycin (sirolimus) in tuberous sclerosis associated pediatric central nervous
      system tumors.
AB  - Tuberous sclerosis complex (TSC) is associated with hamartomatous growths
      including subependymal giant cell astrocytomas (SEGAs). Since chemo-radiation
      therapies offer scant benefit, oncologists had traditionally been little involved
      in managing SEGAs. Recent evidence demonstrating rapamycin efficacy in adults and
      children with TSC-associated tumors foresee a practice change. We summarize our
      institutional experience and literature review that highlight potential benefits
      and hazards of rapamycin therapy, for TSC patients with SEGA, and other syndromal
      brain tumors.

PMID- 19856392
TI  - Adipocytokines in relation to Hodgkin lymphoma in children.
AB  - This case-control study aims to explore the association of serum
      adiponectin/leptin with childhood Hodgkin lymphoma (HL). Study participants were
      75 children with histologically confirmed HL, registered in the Nationwide
      Registry for Childhood Haematological Malignancies and 75 age- and gender-matched
      controls. Multiple conditional logistic regression analyses were performed,
      adjusting for sociodemographic and lifestyle parameters. Adiponectin levels were
      consistently higher among cases in all models with ORs >1.25; 95% CIs ranging
      from 0.9 to 1.8 and P-values from 0.09 to 0.20. By contrast, there was no
      association of serum leptin with HL. In conclusion, elevated serum adiponectin
      might be a risk factor for childhood HL.

PMID- 19856394
TI  - MGMT as a potential stratification marker in relapsed high-grade glioma of
      children: the HIT-GBM experience.
AB  - BACKGROUND: Studies in adults with malignant glioma suggest MGMT methylation as a
      stratification marker. Similar data for children are sparse. We investigated the
      impact of MGMT methylation and expression on survival of children with high-grade
      glioma (HGG) registered into the German HIT-GBM database receiving temozolomide
      (TMZ) as part of their treatment (n = 21 relapsed, n = 4 primary). PROCEDURE:
      Twenty-four patients were included retrospectively. Methylation specific PCR
      (MSP), calibrated combined bisulfite restriction analysis (COBRA), and
      immunohistochemistry (IHC) were applied. Survival analyses were performed by
      Kaplan-Meier and Cox proportional-hazards models. RESULTS: MSP demonstrated DNA
      methylation in 77%. Patients with a methylated MGMT promoter had a sixfold longer
      median EFS (P = 0.015; 5.5 months vs. 0.9 months). Considering the results of
      calibrated COBRA, MGMT methylation was again associated with an elevated EFS (P =
      0.05; 10.2 months vs. 2.6 months) and OS (P = 0.06; 18.7 months vs. 7.2 months)
      only if methylation was >14%. No difference in EFS and OS at all was noted
      between unmethylated and tumors methylated at low level (n = 9). Twenty-two
      tumors were positive by IHC, 10 showed low MGMT expression (IHC score 0-4). We
      did not detect any difference in EFS and OS between moderate/high-expressing
      tumors (IHC score 6-12) and those with low or no expression (IHC score 0-4).
      CONCLUSION: DNA methylation, but not protein expression of MGMT was associated
      with an increased median EFS and OS of children with relapsed HGG. MGMT
      methylation status warrants prospective evaluation as a stratification marker for
      children with HGG.

PMID- 19856395
TI  - Adherence to study medication and visits: data from the BABY HUG trial.
AB  - BACKGROUND: Subject retention and adherence are essential to maintain the power
      and validity of the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). We
      designed a study to assess adherence with study medication administration and
      study visits and to evaluate socioeconomic factors (SES) that may influence these
      measurements of adherence. These data are important for assessing impact of
      adherence on BABY HUG trial outcome and defining impact of SES on adherence.
      METHODS: Each subject's median study medication (MedAd) and mean visit adherence
      (VAd) were evaluated. We examined associations of adherence with SES of
      participating families. RESULTS: MedAd data were available on 153 of the 191
      subjects who started randomized study medication. MedAd was 101.7% of volume
      prescribed, with 88.9% of subjects taking at least 80% of doses. VAd data were
      available on 185 of the 191 subjects who started randomized study medication. VAd
      was 97.3%, with 82.2% of subjects having no missed visits. During dose titration,
      subjects had on average 12.9% higher medication adherence than subjects who were
      on a stable dose and had less frequent study visits. MedAd and VAd were not
      significantly associated with SES. CONCLUSION: Subjects in the BABY HUG trial
      have had excellent adherence. SES was not associated with adherence, suggesting
      that SES should not be used as a criterion for enrolment in clinical trials.
      Additional efforts are needed to maintain medication adherence, particularly when
      the interval between scheduled visits increases. (ClinicalTrials.gov number,
      NCT00006400).

PMID- 19856396
TI  - Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric
      patients in Japan.
AB  - BACKGROUND: Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in
      pediatric patients are relatively rare. PROCEDURE: We performed a retrospective
      analysis in patients with PTCL over an 18-year period (1991-2008). RESULTS: We
      could analyze clinical data in 21 patients with non-anaplastic PTCL; 10 were
      female and 10 male. Median age of onset was 11 years (range: 1-21 years). There
      were nine patients with PTCL, not otherwise specified (PTCL-NOS); ten with
      extranodal NK/T-cell lymphoma, nasal type; one with angioimmunoblastic T-cell
      lymphoma; and one with subcutaneous panniculitis-like T-cell lymphoma. Initial
      lesions involved cervical lymph nodes in five patients, and the skin in five
      patients. In five patients, hemophagocytic syndrome (HPS) was the initial
      clinical feature. There were 12 patients with advanced stage disease (stages III
      and IV). Chemotherapy and radiation was administered in 18 and 2 patients,
      respectively. Among the two patients who did not receive chemotherapy and
      radiation, one patient died while being treated for HPS but another improved
      spontaneously. Although 5 patients relapsed, 18 of 21 patients remained alive
      without disease at last follow-up. Five-year overall survival rate was 85.2%.
      CONCLUSIONS: Generally, the outcome results of conventional chemotherapy for high
      risk PTCL are poor in adult patients. However, the excellent results in our study
      suggest that PTCL of childhood is quite different from that of adulthood.
      Although this study is first report about PTCL of Asian children, the number of
      patients was small in this study. Larger studies are needed to confirm these
      findings.

PMID- 19856397
TI  - Ewing sarcoma of the neck.

PMID- 19856398
TI  - Epithelial differentiation of adipose-derived stem cells for laryngeal tissue
      engineering.
AB  - OBJECTIVES/HYPOTHESIS: One potential treatment option for severe vocal fold
      scarring is to replace the vocal fold cover layer with a tissue-engineered
      structure containing autologous cells. As a first step toward that goal, we
      sought to develop a three-dimensional cell-populated matrix resembling the vocal
      fold layers of lamina propria and epithelium. STUDY DESIGN: Basic science
      investigation. METHODS: Adipose-derived stem cells were cultured in fibrin
      hydrogels with various growth factors. At the end of the culture period, matrices
      were sectioned and labeled with immunomarkers to identify cell phenotype.
      RESULTS: Adipose-derived stem cells survived, attached, and populated three
      dimensional fibrin matrices. Under select conditions, a superficial layer of
      cells expressing epithelial marker proteins overlay a deeper mesenchymal cell
      layer. CONCLUSIONS: A three-dimensional structure of fibrin and adipose-derived
      stem cells was created as a prototype vocal fold replacement. Two segregated cell
      phenotypes occurred, producing a bilayered structure resembling epithelium over
      lamina propria. This preliminary work demonstrates the feasibility of tissue
      engineering to produce structures for vocal fold replacement.

PMID- 19856400
TI  - Wilms tumor, AML, and medulloblastoma in a child with cancer prone syndrome of
      total premature chromatid separation and Fanconi anemia.

PMID- 19856402
TI  - Effect of polyethylene glycol on the thermal stability of green fluorescent
      protein.
AB  - Green fluorescent protein (GFP) shows remarkable structural stability and high
      fluorescence; its stability can be directly related to its fluorescence output,
      among other characteristics. GFP is stable under increasing temperatures, and its
      thermal denaturation is highly reproducible. Some polymers, such as polyethylene
      glycol, are often used as modifiers of characteristics of biological
      macromolecules, to improve the biochemical activity and stability of proteins or
      drug bioavailability. The aim of this study was to evaluate the thermal stability
      of GFP in the presence of different PEG molar weights at several concentrations
      and exposed to constant temperatures, in a range of 70-95 degrees C. Thermal
      stability was expressed in decimal reduction time. It was observed that the D
      values obtained were almost constant for temperatures of 85, 90, and 95 degrees
      C, despite the PEG concentration or molar weight studied. Even though PEG can
      stabilize proteins, only at 75 degrees C, PEG 600 and 4,000 g/mol stabilized GFP.

PMID- 19856403
TI  - Exploiting the intracellular compartmentalization characteristics of the S.
      cerevisiae host cell for enhancing primary purification of lipid-envelope virus
      like particles.
AB  - This article demonstrates how the intracellular compartmentalization of the S.
      cerevisiae host cell can be exploited to impart selectivity during the primary
      purification of lipid-envelope virus-like particles (VLPs). The hepatitis B
      surface antigen (HBsAg) was used as the VLP model in this study. Expressed HBsAg
      remain localized on the endoplasmic reticulum and the recovery process involves
      treating cell homogenate with a detergent for HBsAg liberation. In our proposed
      strategy, a centrifugation step is introduced immediately following cell
      disruption but prior to the addition of detergent to allow the elimination of
      bulk cytosolic contaminants in the supernatant, achieving approximately 70%
      reduction of contaminating yeast proteins, lipids, and nucleic acids. Recovery
      and subsequent treatment of the solids fraction with detergent then releases the
      HBsAg into a significantly enriched product stream with a yield of approximately
      80%. The selectivity of this approach is further enhanced by operating under
      moderate homogenization pressure conditions ( approximately 400 bar). Observed
      improvements in the recovery of active HBsAg and reduction of contaminating host
      lipids were attributed to the low-shear conditions experienced by the HBsAg
      product and reduced cell fragmentation, which led to lower coextraction of lipids
      during the detergent step. As a result of the cleaner process stream, the level
      of product capture during the loading stage of a downstream hydrophobic
      interaction chromatography stage increased by two-fold leading to a concomitant
      increase in the chromatography step yield. The lower level of exposure to
      contaminants is also expected to improve column integrity and lifespan.

PMID- 19856404
TI  - MRI: a charmed past and an exciting future.
AB  - The invention and development of MRI took place under very desirable
      circumstances. Dr. Lauterbur, a distinguished NMR chemist, conceived of the basic
      idea. Once this concept was presented to the medical imaging community, a
      wonderful synergy developed between the two mature disciplines of NMR physical
      chemistry and medical imaging. This resulted in amazingly rapid progress and
      acceptance by the clinical community. This adventure is in sharp contrast to the
      history of x-ray imaging. This began with the accidental discovery of x-rays by
      Roentgen at the end of the 19th century. Unlike NMR, the basic x-ray mechanism
      was not understood and was mistakenly thought to not be an electromagnetic wave.
      MRI is now at an advanced stage where investigators study advanced hardware and
      software improvements. These studies include improved signal-to-noise ratio,
      resolution, and speed, which generally involve higher B(0). The high readout
      field results in numerous problems. These can be overcome by prepolarizing
      techniques using a high polarization field and a relatively low readout field.

PMID- 19856405
TI  - Advances in office-based diagnosis and treatment in laryngology.

PMID- 19856406
TI  - 7 Tesla MR imaging of the human eye in vivo.
AB  - PURPOSE: To develop a protocol which optimizes contrast, resolution and scan time
      for three-dimensional (3D) imaging of the human eye in vivo using a 7 Tesla (T)
      scanner and custom radio frequency (RF) coil. MATERIALS AND METHODS: Initial
      testing was conducted to reduce motion and susceptibility artifacts. Three
      dimensional FFE and IR-TFE images were obtained with variable flip angles and TI
      times. T(1) measurements were made and numerical simulations were performed to
      determine the ideal contrast of certain ocular structures. Studies were performed
      to optimize resolution and signal-to-noise ratio (SNR) with scan times from 20 s
      to 5 min. RESULTS: Motion and susceptibility artifacts were reduced through
      careful subject preparation. T(1) values of the ocular structures are in line
      with previous work at 1.5T. A voxel size of 0.15 x 0.25 x 1.0 mm(3) was obtained
      with a scan time of approximately 35 s for both 3D FFE and IR-TFE sequences.
      Multiple images were registered in 3D to produce final SNRs over 40. CONCLUSION:
      Optimization of pulse sequences and avoidance of susceptibility and motion
      artifacts led to high quality images with spatial resolution and SNR exceeding
      prior work. Ocular imaging at 7T with a dedicated coil improves the ability to
      make measurements of the fine structures of the eye.

PMID- 19856407
TI  - Prediction of hemorrhagic transformation in acute ischemic stroke using texture
      analysis of postcontrast T1-weighted MR images.
AB  - PURPOSE: To test the hypothesis that texture analysis of postcontrast T1-weighted
      MR images will predict hemorrhagic transformation (HT) in patients with acute
      ischemic stroke (AIS) with better accuracy than visual evidence of contrast
      enhancement (VE). MATERIALS AND METHODS: Thirty-four AIS patients were examined
      within 3.5 +/- 1.5 h after stroke. T1-weighted MR images were acquired 19 +/- 7
      min postcontrast injection. HT was determined by follow-up imaging at 24-72 h.
      Postcontrast images were evaluated for VE. Four second-order textural features
      were extracted (f1, f2, f3, and f9) for each patient. Receiver operating
      characteristic (ROC) curves were constructed for VE and for textural features,
      with HT as the outcome measure. RESULTS: The f2 for HT patients (n = 12) was
      significantly lower than in non-HT patients (1058 +/- 356 versus 1568 +/- 527; P
      = 0.005); the converse was true for f3 (0.67 +/- 0.12 versus 0.54 +/- 0.13; P =
      0.007). ROC analysis indicated that the f2 and f3 textural features were the only
      two significant predictors of HT (P = 0.0018 and P = 0.0042). The addition of VE
      to either f2 or f3 did not result in a significant improvement in accuracy.
      CONCLUSION: Texture analysis of postcontrast T1-weighted images may be superior
      to visual evidence of enhancement for the prediction of HT.

PMID- 19856408
TI  - 3D velocity quantification in the heart: improvements by 3D PC-SSFP.
AB  - PURPOSE: To test whether a 3D imaging sequence with phase contrast (PC) velocity
      encoding based on steady-state free precession (SSFP) improves 3D velocity
      quantification in the heart compared to the currently available gradient echo
      (GE) approach. MATERIALS AND METHODS: The 3D PC-SSFP sequence with 1D velocity
      encoding was compared at the mitral valve in 12 healthy subjects with 3D PC-GE at
      1.5T. Velocity measurements, velocity-to-noise-ratio efficiency (VNR(eff)), intra
      and interobserver variability of area and velocity measurements, contrast-to
      noise-ratio (CNR), and artifact sensitivity were evaluated in both long- and
      short-axis orientation. RESULTS: Descending aorta mean and peak velocities
      correlated well (r(2) = 0.79 and 0.93) between 3D PC-SSFP and 3D PC-GE. At the
      mitral valve, mean velocity correlation was moderate (r(2) = 0.70 short axis,
      0.56 long axis) and peak velocity showed good correlation (r(2) = 0.94 short
      axis, 0.81 long axis). In some cases VNR(eff) was higher, in others lesser,
      depending on slab orientation and cardiac phase. Intra- and interobserver
      variability was generally better for 3D PC-SSFP. CNR improved significantly,
      especially at end systole. Artifact levels did not increase. CONCLUSION: 3D SSFP
      velocity quantification was successfully tested in the heart. Blood-myocardium
      contrast improved significantly, resulting in more reproducible velocity
      measurements for 3D PC-SSFP at 1.5T.

PMID- 19856409
TI  - Cardiac function by MRI in congenital heart disease: impact of consensus training
      on interinstitutional variance.
AB  - PURPOSE: To investigate the impact of interinstitutional variance (=interobserver
      variance between institutions) for volumetric and flow cardiac MR (CMR) data and
      if training on image reading could improve bias. MATERIALS AND METHODS: In a
      three-center study, a total of 32 adults with repaired Tetralogy of Fallot and 23
      controls underwent CMR using standardized protocols for ventricular volumes/mass
      (by transverse and short-axis cine-MRI) and pulmonary/aortic blood flow by
      velocity-encoded MRI (VEC-MRI). Data were analyzed blinded and independently in
      each institution by experienced readers. Interinstitutional variance was
      determined before/after training on consented guidelines for image analysis.
      RESULTS: In patients, initial interinstitutional variability of right ventricular
      parameters was substantial but decreased by training. On transverse planes,
      variation coefficient for end-diastolic/systolic volumes and ejection fraction
      decreased from 22%, 19%, and 19% to 7%, 10%, and 8%, respectively (P < 0.025).
      Left-ventricular variation coefficients improved for end-diastolic and stroke
      volumes from 8% and 15% to 4% and 6%, respectively (P < 0.007). For short-axis
      volumetry training resulted in narrowed limits of confidence. Variability did not
      significantly change in the controls. There was no significant difference between
      transverse/short-axis MRI. Interinstitutional variance for VEC-MRI in
      patients/controls was low (<4%). CONCLUSION: Interinstitutional variance is an
      important source of variability in volumetric but not in flow CMR. Such variance
      can be reduced effectively by consented training.

PMID- 19856410
TI  - Tissue factor -1208D>I polymorphism is associated with D-dimer levels in patients
      with inflammatory bowel disease.

PMID- 19856411
TI  - Novel model of TH2-polarized chronic ileitis: the SAMP1 mouse.
AB  - BACKGROUND: SAMP1/Yit mice develop spontaneous, segmental, transmural ileitis
      recapitulating many features of Crohn's disease (CD). The ileitic phenotype may
      have arisen during crosses of SAMP1 mice selected for the presence of skin
      lesions. We hereby describe that the original SAMP1 strain similarly develops
      ileitis. Our aim was to characterize the histopathological and immunological
      features of this model and assess its responsiveness to standard inflammatory
      bowel disease (IBD) therapy. METHODS: The time course of histopathological
      features of ileitis was assessed. Immune compartments were characterized by flow
      cytometry. Ileal cytokine profiles and transcription factors were determined by
      real-time reverse-transcription polymerase chain reaction (RT-PCR). Finally,
      response to corticosteroid therapy and its effect on immune compartments and
      cellularity was evaluated. RESULTS: Histological features and time course of
      disease were conserved, compared to those reported in SAMP1/Yit strains, with
      similar expansion of CD19+, CD4+, and CD8+ effector (CD44(high) CD62L(low)), and
      central memory lymphocytes (CD44(high)CD62L(high)). However, different from
      SAMP1/YitFc mice, analysis of ileal cytokine profiles revealed initial T(H)1
      polarization followed by T(H)2-polarized profile accompanied by prominent
      eosinophilia during late disease. Lastly, corticosteroids attenuated ileitis,
      resulting in decreased lymphocyte subsets and cellularity of compartments.
      CONCLUSIONS: Here we report that the ileitic phenotype of SAMP1-related strains
      was already present in the original SAMP1 strain. By contrast, the cytokine
      profile within the terminal ilea of SAMP1 is distinct from the mixed T(H)1/T(H)2
      profile of SAMP1/YitFc mice during late disease, as it shows predominant T(H)2
      polarization. Dissemination of these strains may advance our understanding of CD
      pathogenesis, which in 60% of patients involves the terminal ileum.

PMID- 19856412
TI  - Utility of phase contrast MR imaging for assessment of pulmonary flow and
      pressure estimation in patients with pulmonary hypertension: comparison with
      right heart catheterization and echocardiography.
AB  - PURPOSE: To compare the utility of phase contrast MR imaging (PC-MRI) for
      assessment of pulmonary flow and pressure estimation with that of right heart
      catheterization and echocardiography (cardiac US) in patients with pulmonary
      arterial hypertension (PAH). MATERIALS AND METHODS: Twenty consecutive patients
      with suspected PAH underwent PC-MRI, cardiac US, and right heart catheterization.
      In each patient, PC-MRI was acquired by cine 2D-PC method on a 1.5 Tesla scanner,
      and stroke volume (SV) and pulmonary arterial systolic pressure (PASP) were
      assessed by using the modified Bernoulli's equation. To evaluate the agreements
      of SV and PASP among the three methods, correlations and limits of agreement
      among the three methods were statistically assessed by using the Bland-Altman's
      analyses. RESULTS: The correlations and limits of agreement for SV and PASP
      between PC-MRI and catheterization (r = 0.96, r(2) = 0.94, 1.1 +/- 6.9 mL and r =
      0.94, r(2) = 0.88, -3.2 +/- 14.5 mmHg, respectively) were better than between
      cardiac US and catheterization (r = 0.01, r(2) < 0.01, 8.9 +/- 42.1 mL and r =
      0.86, r(2) = 0.72, -5.9 +/- 27.7 mmHg, respectively). CONCLUSION: PC-MRI is more
      compatible with right heart catheterization than cardiac US in pulmonary flow and
      pressure estimation.

PMID- 19856413
TI  - Relationship of temporal resolution to diagnostic performance for dynamic
      contrast enhanced MRI of the breast.
AB  - PURPOSE: To investigate the relationship between temporal resolution of dynamic
      contrast-enhanced (DCE) magnetic resonance imaging (MRI) and classification of
      breast lesions as benign versus malignant. MATERIALS AND METHODS: Patients
      underwent T(1)-weighted DCE MRI with 15 s/acquisition temporal resolution using
      1.5 Tesla (n = 48) and 3.0T (n = 33) MRI scanners. Seventy-nine patients had
      pathologically proven diagnosis and 2 had 2 years follow-up showing no change in
      lesion size. The temporal resolution of DCE MRI was systematically reduced as a
      postprocessing step from 15 to 30, 45, and 60 s/acquisition by eliminating
      intermediate time points. Average wash-in and wash-out slopes, wash-out
      percentage changes, and kinetic curve shape (persistently enhancing, plateau, or
      wash-out) were compared for each temporal resolution. Logistic regression and
      receiver operating characteristic (ROC) curve analysis were used to compare
      kinetic parameters and diagnostic accuracy. RESULTS: Sixty patients (74%) had
      malignant lesions and 21 patients (26%) had benign lesions. All temporal
      resolution parameters significantly predicted benign versus malignant diagnosis
      (P < 0.05). However, 45 s/acquisition and higher temporal-resolution datasets
      showed higher accuracy than the 60 s/acquisition dataset by ROC curve analysis
      (0.72 versus 0.69 for average wash-in slope; 0.85 versus 0.82, for average wash
      out slope; and 0.88 versus 0.80 for kinetic curve shape assessment, for 45
      s/acquisition versus 60 s/acquisition temporal-resolution datasets, respectively
      (P = 0.027). CONCLUSION: DCE MRI data with at least 45-s temporal resolution
      maximized the agreement between the kinetic parameters and correct classification
      of benign versus malignant diagnosis.

PMID- 19856414
TI  - MDP-NOD2 stimulation induces HNP-1 secretion, which contributes to NOD2
      antibacterial function.
AB  - BACKGROUND: Human neutrophil peptide 1 (HNP-1) is a defensin with antibacterial
      activity secreted by various cells as a component of the innate immune host
      defense. NOD2 is a cytoplasmic protein that recognizes bacterial derived muramyl
      dipeptide, and is involved in bacterial clearance. The aim of the present study
      was to investigate the relationship between antibacterial activity of NOD2 and
      HNP-1 expression in epithelial cell lines. METHODS: Gentamicin protection assay
      using Salmonella typhimurium was performed in Caco-2 cells. The mRNA level was
      determined by quantitative reverse-transcription polymerase chain reaction (RT
      PCR) and defensin expression was assessed by Western blot and enzyme-linked
      immunosorbent assay (ELISA). Nuclear factor-kappaB activation was assessed using
      pIV luciferase and Renilla plasmids. A NOD2 mutant was generated by site-directed
      mutagenesis. RESULTS: Among the defensins tested, only HNP-1 expression is
      induced in colonic epithelial model HCT116 cells after MDP-LD stimulation. HNP-1
      secretion is significantly increased after MDP-LD stimulation in the cell
      supernatant of intestinal epithelial cells expressing endogenous NOD2, but not in
      cells that lack endogenous NOD2 expression. HNP-1 is required for NOD2-dependent
      NF-kappaB activation after MDP-LD stimulation since hnp-1 siRNA transfection
      abrogated the response to MDP-LD stimulation. The antibacterial function of NOD2
      against S. typhimurium was impaired when expression of HNP-1 was blocked by
      siRNA. CONCLUSIONS: HNP-1 secretion depends on NOD2 stimulation by MDP-LD and
      contributes to antibacterial activity in intestinal epithelial cells expressing
      endogenous NOD2, but not NOD2 3020insC mutant associated with increased
      susceptibility to Crohn's disease.

PMID- 19856415
TI  - A33 antigen-deficient mice have defective colonic mucosal repair.
AB  - BACKGROUND: A33 antigen is a transmembrane protein expressed predominantly in
      normal intestinal epithelium and most colon cancers and cell lines. The function
      of A33 antigen is unclear, but indirect evidence indicates a role in cell
      adhesion, trafficking, and the gut immune response. The aim of this study was to
      determine the contribution made by A33 antigen in mediating colonic repair
      following colitis induction in the A33 antigen-deficient mutant mouse. METHODS:
      Colitis was induced by treatment with TNBS/ethanol. A33 antigen-deficient or
      wildtype mice were sacrificed at 0, 3, 7, and 14 days after colitis induction and
      morphological damage, mucosal proliferation, and inflammatory cell infiltration
      were quantified. In a subsequent study, following the induction of colitis mice
      were monitored for 22 days and morbidity and mortality determined. RESULTS: Mice
      lacking A33 antigen expression were compromised in their ability to resolve TNBS
      induced damage and exhibited distinct crypt pathology. In A33 antigen-deficient
      mice morphological damage remained unresolved at 14 days postcolitis induction.
      Increases in colonic cell proliferation were delayed in A33 antigen-deficient
      mice, and the rate of crypt fission was increased after TNBS treatment.
      Commensurate with these observations, polymorphonuclear cell infiltration was
      suppressed in the absence of A33 antigen. Mortality following colitis induction
      was 20% higher in A33 antigen-deficient mice than in wildtype controls.
      CONCLUSIONS: Mice deficient in A33 antigen expression show impaired resolution of
      hapten-induced mucosal damage, leading to increased mortality, associated with
      impaired epithelial cell proliferation and a suppressed adaptive immune response.
      This study suggests a contribution for A33 antigen in the colonic healing
      response following mucosal damage.

PMID- 19856416
TI  - Cdcs1 a major colitis susceptibility locus in mice; subcongenic analysis reveals
      genetic complexity.
AB  - BACKGROUND: The cytokine-deficiency-induced colitis susceptibility (Cdcs)1 locus
      is a major modifier of murine inflammatory bowel disease (IBD) and was originally
      identified in experimental crosses of interleukin-10-deficient (Il10(-/-)) mice.
      Congenic mice, in which this locus was reciprocally transferred between IBD
      susceptible C3H/HeJBir-Il10(-/-) and resistant C57BL/6J-Il10(-/-) mice, revealed
      that this locus likely acts by inducing innate hypo- and adaptive
      hyperresponsiveness, associated with impaired NF-kappaB responses of macrophages.
      The aim of the present study was to dissect the complexity of Cdcs1 by further
      development and characterization of reciprocal Cdcs1 congenic strains and to
      identify potential candidate genes in the congenic interval. METHODS: In total,
      15 reciprocal congenic strains were generated from Il10(-/-) mice of either
      C3H/HeJBir or C57BL/6J genetic backgrounds by 10 cycles of backcrossing. Colitis
      activity was monitored by histological grading. Candidate genes were identified
      by fine mapping of congenic intervals, sequencing, microarray analysis, and a
      high-throughput real-time reverse-transcription polymerase chain reaction (RT
      PCR) approach using bone marrow-derived macrophages. RESULTS: Within the
      originally identified Cdcs1-interval, 3 independent regions were detected that
      likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and
      Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3,
      Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in
      coding or regulatory regions and expression differences between susceptible and
      resistant mouse strains. CONCLUSIONS: Subcongenic analysis of the major
      susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic
      structure. Candidate gene approaches revealed attractive genes within the
      identified regions.

PMID- 19856417
TI  - Shorter difference between myocardium and blood optimal inversion time suggests
      diffuse fibrosis in dilated cardiomyopathy.
AB  - PURPOSE: To find evidence of diffuse fibrosis in dilated cardiomyopathy (DCM)
      patients by comparing measurements on clinical late gadolinium enhancement (LGE)
      cardiovascular magnetic resonance (CMR) studies between DCM and healthy subjects.
      MATERIALS AND METHODS: LGE-CMR and the Look-Locker images from 20 DCM patients
      and 17 healthy controls were analyzed. Blood signal-to-noise ratio (SNR),
      myocardium SNR, and blood-to-myocardium contrast-to-noise ratio (CNR) were
      measured on the LGE-CMR images. The optimal inversion time (TI) to null blood and
      myocardium was determined on the Look-Locker images. The postcontrast T(1) was
      estimated using a phantom study that correlated optimal TI and heart rate to
      T(1). RESULTS: The blood SNR was lower, myocardium SNR was higher, and the blood
      to-myocardium CNR was lower (6.6 +/- 0.7 vs. 10.3 +/- 0.9, P = 0.004) on DCM LGE
      CMR images as compared to controls. The blood-myocardium optimal TI difference
      (DeltaTI) was lower (38 +/- 2 msec vs. 55 +/- 3 msec, P < 0.001) in DCM, and the
      estimated blood-myocardium T(1) difference (DeltaT(1)) (116 +/- 6 msec vs. 152 +/
      8 msec, P = 0.001) was also lower. CONCLUSION: DCM patients have reduced blood
      myocardium DeltaTI and DeltaT(1), and lower CNR as compared to controls,
      suggesting the presence of diffuse fibrosis. This may impact the interpretation
      of LGE data.

PMID- 19856418
TI  - Assessment of hyperpolarized 3He lung MRI for regional evaluation of
      interventional therapy: a pilot study in pediatric cystic fibrosis.
AB  - PURPOSE: To determine whether regional changes in lung ventilation in a group of
      pediatric cystic fibrosis (CF) patients following a course of chest physiotherapy
      could be detected with (3)He MRI. MATERIALS AND METHODS: The reproducibility of
      lung ventilation volume measurements obtained with (3)He lung magnetic resonance
      imaging (MRI) was established in a group of five children with CF age 6-15 years.
      The same methodology was then used to evaluate whether standard chest
      physiotherapy (percussion and drainage) had any immediate effect on regional
      ventilated lung volumes in a further group of nine age-matched CF children (5-15
      years). RESULTS: Global lung ventilation volumes remained the same within the
      limits of sensitivity derived from the reproducibility study; however, regional
      lung ventilation was observed to change in most patients after therapy.
      CONCLUSION: (3)He MRI can be successfully used in children with CF, and has the
      sensitivity to detect regional quantitative changes in lung ventilation following
      chest physiotherapy.

PMID- 19856420
TI  - Surgery for low-grade colorectal dysplasia in ulcerative colitis: decisions,
      decisions.

PMID- 19856419
TI  - Principal component analysis of breast DCE-MRI adjusted with a model-based
      method.
AB  - PURPOSE: To investigate a fast, objective, and standardized method for analyzing
      breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) applying
      principal component analysis (PCA) adjusted with a model-based method. MATERIALS
      AND METHODS: 3D gradient-echo DCE breast images of 31 malignant and 38 benign
      lesions, recorded on a 1.5T scanner, were retrospectively analyzed by PCA and by
      the model-based three-timepoints (3TP) method. RESULTS: Intensity-scaled (IS) and
      enhancement-scaled (ES) datasets were reduced by PCA yielding a first IS
      eigenvector that captured the signal variation between fat and fibroglandular
      tissue; two IS-eigenvectors and the two first ES-eigenvectors captured contrast
      enhanced changes, whereas the remaining eigenvectors captured predominantly noise
      changes. Rotation of the two contrast-related eigenvectors led to a high
      congruence between the projection coefficients and the 3TP parameters. The ES
      eigenvectors and the rotation angle were highly reproducible across malignant
      lesions, enabling calculation of a general rotated eigenvector base. Receiver
      operating characteristic (ROC) curve analysis of the projection coefficients of
      the two eigenvectors indicated high sensitivity of the first rotated eigenvector
      to detect lesions (area under the curve [AUC] > 0.97) and of the second rotated
      eigenvector to differentiate malignancy from benignancy (AUC = 0.87). CONCLUSION:
      PCA adjusted with a model-based method provided a fast and objective computer
      aided diagnostic tool for breast DCE-MRI.

PMID- 19856421
TI  - Combination of MUC5ac and WT-1 immunohistochemistry is useful in distinguishing
      pancreatic ductal carcinoma from ovarian serous carcinoma in effusion cytology.
AB  - Malignant ascites may be the first presentation of an unsuspected cancer.
      Pancreas and ovary are among the organs that are usually evaluated as a source of
      primary. The purpose of this study is to investigate a panel of
      immunohistochemical stains to help differentiate pancreatic from ovarian
      carcinoma. We evaluated the immunohistochemical staining of eight commercially
      available antibodies MUC1, MUC2, MUC5ac, Wilm's tumor susceptibility gene 1
      (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with
      evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9
      pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous
      carcinomas were positive for WT-1 (100%), CK7 (93%), CK20 (43%), CA125 (100%),
      CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic
      carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7
      (78%), CK20 (22%), CA125 (89%), WT-1 (0%), and MUC 2 (0%). The combination of
      MUC5ac positivity/WT-1 negativity was seen in 100% of pancreatic carcinoma,
      whereas MUC5ac negativity/WT-1 positivity in 100% of ovarian serous carcinoma. It
      appears that the combination of MUC5ac and WT-1 stains is useful in
      distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid
      cytology.

PMID- 19856422
TI  - Respiratory cytology: differential diagnosis and pitfalls.
AB  - Pulmonary cytology can be challenging and has its share of diagnostic pitfalls.
      Reactive atypia can occasionally be alarming, leading to diagnostic pitfall for a
      false-positive diagnosis of malignancy, even for experienced cytopathologists
      (Naryshkin and Young, Diagn Cytopathol 1993;9:89-97). In addition, cytologic
      preparations can show an absence of architectural clues, leading to diagnostic
      difficulties. Some conditions can cytologically as well as clinically and
      radiographically mimic malignancies, making these pitfalls even more frequent
      (Bedrossian et al., Lab Med 1983;14:86-95). A recent report stated that "no
      laboratory that aims to make definitive diagnoses in pulmonary cytology can be
      spared from false-positive results"(Policarpio-Nicolas and Wick, Diagn Cytopathol
      2008;36:13-19). A false-positive finding could produce unnecessary treatment and
      morbidity, whereas false-negative diagnosis could result in delayed diagnosis and
      treatment. This review analyzes and illustrates cellular changes and benign
      entities that can mimic malignancy in respiratory cytology as well as neoplasms
      that could lead to a false-negative diagnosis. In addition, some specific
      challenging and difficult aspects in classification of pulmonary malignancies
      will be discussed. Guidelines and clues are presented to avoid such pitfalls.

PMID- 19856423
TI  - Living with uncertainty: equivocal Pap test results and the evolution of ASC
      terminology.
AB  - Communication of equivocal findings and their significance has been a significant
      challenge related to Pap testing throughout its history. Terminology to report
      these findings has changed considerably to accommodate the changes in
      understanding of cervical neoplasia, and to accommodate new management
      strategies, tests, and technologies. This article reviews the evolution of
      terminology for equivocal Pap test findings from the original Papanicolaou
      classification to the current the Bethesda System 2001 atypical squamous cells
      terminology, the implication and use of these terms, and the changing landscape
      of cervical neoplasia screening, which prompted these terminology changes.
      Emerging issues related to improving risk stratification through the introduction
      of additional terms and the impact of human papillomavirus testing may alter
      terminology of equivocal findings in the future.

PMID- 19856424
TI  - Body size and human energy requirements: Reduced mass-specific total energy
      expenditure in tall adults.
AB  - Mammalian resting energy expenditure (REE) increases as approximately
      weight(0.75) while mass-specific REE scales as approximately weight(-0.25).
      Energy needs for replacing resting losses are thus less relative to weight (W) in
      large compared with small mammals, a classic observation with biological
      implications. Human weight scales as approximately height(2) and tall adults thus
      have a greater weight than their short counterparts. However, it remains unknown
      if mass-specific energy requirements are less in tall adults; allometric models
      linking total energy expenditure (TEE) and weight with height (H) are lacking. We
      tested the hypothesis that mass-specific energy requirements scale inversely to
      height in adults by evaluating TEE (doubly labeled water) data collected by the
      National Academy of Sciences. Activity energy expenditure (AEE) was calculated
      from TEE, REE (indirect calorimetry), and estimated diet-induced energy
      expenditure. Main analyses focused on nonmorbidly obese subjects < or =50 yrs of
      age with non-negative AEE values (n = 404), although results were directionally
      similar for all samples. Allometric models, including age as a covariate,
      revealed significantly (P < 0.05) greater REE, AEE, and TEE as a function of
      height (range H(1.5-1.7)) in both men and women. TEE/W scaled negatively to
      height ( approximately H(-0.7), P < 0.01) with predicted mass-specific TEE
      (kcal/kg/d) at +/-2 SD for US height lower in tall compared with short men (40.3
      vs. 46.5) and women (37.7 vs. 42.7). REE/W also scaled negatively to height in
      men (P < 0.001) and women (P < 0.01). Results were generally robust across
      several different analytic strategies. These observations reveal previously
      unforeseen associations between human stature and energy requirements that have
      implications for modeling efforts and provide new links to mammalian biology as a
      whole.

PMID- 19856425
TI  - Change in waist circumference over 11 years and current waist circumference
      independently predict elevated CRP in Filipino women.
AB  - C-reactive protein, a marker of chronic, low-grade inflammation, is strongly
      associated with current central adiposity, and has been linked to elevated risk
      of cardiovascular disease. Less is known about the contribution of longitudinal
      change in waist circumference to current inflammation. We evaluated the extent to
      which current waist circumference and change over an 11-year interval contribute
      independently to low-grade systemic inflammation measured in a group of 1,294
      women, 35-69 years, participating in the Cebu Longitudinal Nutrition and Health
      Survey in the Philippines. Waist circumference was measured at the time of blood
      draw for CRP analysis in 2005 and during an earlier survey in 1994. A waist
      circumference delta variable was constructed by subtracting current circumference
      from past circumference. We used logistic regression models to predict having an
      elevated plasma CRP concentration (3 mg L(-1) < CRP < 10 mg L(-1)). Waist
      circumference in 2005 was a strong predictor of elevated CRP (OR 1.10, 95% CI =
      1.08, 1.12, P < 0.001). In combined models, increase in circumference over 11
      years was a significant and independent predictor of elevated CRP risk (OR =
      1.023, 95% CI = 1.00, 1.05, P < 0.05). Considering the average increase over
      time, the cumulative risk of elevated CRP due to increased central adiposity was
      25.7%. However, women who reduced their waist circumference between 1994 and 2005
      had greatly reduced risk (6.2%), suggesting that even long-term inflammatory
      burden can be reversed by weight loss. Although current waist circumference is an
      important contributor to risk of elevated systemic inflammation in this as in
      other populations, history of central adiposity may be an independent phenomenon.

PMID- 19856427
TI  - Uncertainty and discordance in the staging and prognosis of diffuse large B-cell
      lymphoma with isolated bilateral testicular involvement.

PMID- 19856426
TI  - Growth patterns in early childhood and final attained stature: data from five
      birth cohorts from low- and middle-income countries.
AB  - Growth failure is cumulative, and short stature is associated with multiple
      indices of reduced human capital. Few studies have been able to address in a
      single analysis both consideration of the timing of growth failure and comparison
      across populations. We analyzed data from birth cohorts in Brazil, Guatemala,
      India, the Philippines, and South Africa (n = 4,659). We used data on length at
      birth (available for three of the five cohorts), 12 mo, 24 mo, and mid-childhood
      to construct cohort- and sex- specific conditional length measures. We modeled
      adult height as a function of conditional length in childhood. The five cohorts
      experienced varying degrees of growth failure. As adults, the Brazil sample was
      0.35 +/- 0.89 standard deviations (SD) below the World Health Organization
      reference, while adult Guatemalans were 1.91 +/- 0.87 SD below the reference. All
      five cohorts experienced a nadir in height for age Z-score at 24 mo. Birth length
      (in the three cohorts with this variable), and conditional length at 12 mo (in
      all five cohorts) were the most strongly associated with adult height. Growth in
      the periods 12-24 mo and 24 mo to mid-childhood showed inconsistent patterns
      across tertiles of adult height. Despite variation in the magnitude of cumulative
      growth failure across cohorts, the five cohorts show highly consistent age
      specific associations with adult stature. Growth failure prior to age 12 mo was
      most strongly associated with adult stature. These consistencies speak to the
      importance of interventions to address intrauterine growth failure and growth
      failure in the first 12 mo of life.

PMID- 19856428
TI  - Conservative management of an extensive renal graft subcapsular hematoma arising
      during living donor nephrectomy. Role of Doppler sonographic posttransplant
      follow-up.
AB  - We report a case of subcapsular hematoma (SH) of a kidney graft arising during
      minimal-incision living-donor nephrectomy. SH covered at least two-thirds of the
      cortical surface. Capsulotomy was not done because it was deemed too risky. In
      the immediate postoperative period, a rapid deterioration of graft function was
      observed associated with Doppler sonographic evidence of graft compression.
      However, in the following days, spontaneous resolution of SH and progressive
      improvement of Doppler findings was observed, which preceded full recovery of
      graft function. Conservative management seemed a valid approach of this
      complication in this case where Doppler sonography proved essential for the
      follow-up.

PMID- 19856429
TI  - Treatment of an extracapsular post-renal biopsy pseudoaneurysm with ultrasound
      guided thrombin injection.
AB  - Percutaneous renal biopsy is a convenient method to obtain allograft tissue for
      histologic evaluation. Vascular complications, such as arteriovenous (AV) fistula
      and pseudoaneurysm, following renal biopsy are well known, and they usually
      resolve without further intervention. When symptomatic, they should be treated.
      We present a patient on chronic anticoagulation who developed a pseudoaneurysm
      after percutaneous renal biopsy. Applying techniques learned in the management of
      femoral artery pseudoaneurysm, we treated our patient with ultrasound-guided
      thrombin injection.

PMID- 19856430
TI  - Another quest for a solution... and when a dedicated device?

PMID- 19856431
TI  - Diffusion-weighted MR imaging of the liver at 3.0 Tesla using TRacking Only
      Navigator echo (TRON): a feasibility study.
AB  - PURPOSE: To assess the feasibility of TRacking Only Navigator echo (TRON) for
      diffusion-weighted magnetic resonance imaging (DWI) of the liver at 3.0T.
      MATERIALS AND METHODS: Ten volunteers underwent TRON, respiratory triggered, and
      free breathing DWI of the liver at 3.0 Tesla (T). Scan times were measured. Image
      sharpness, degree of stair-step and stripe artifacts for the three methods were
      assessed by two observers. RESULTS: Mean scan times of TRON and respiratory
      triggered DWI relative to free breathing DWI were 34% and 145% longer
      respectively. In four of eight comparisons (two observers, two b-values, two
      slice orientations), TRON DWI image sharpness was significantly better than free
      breathing DWI, but inferior to respiratory triggered DWI. In two of four
      comparisons (two observers, two b-values), degree of stair-step artifacts in TRON
      DWI was significantly lower than in respiratory triggered DWI. Degree of stripe
      artifacts between the three methods was not significantly different. CONCLUSION:
      DWI of the liver at 3.0T using TRON is feasible. Image sharpness in TRON DWI is
      superior to that in free breathing DWI. Although image sharpness of respiratory
      triggered DWI is still better, TRON DWI requires less scan time and reduces stair
      step artifacts.

PMID- 19856432
TI  - High-b-value diffusion-weighted MR imaging of hepatocellular lesions: estimation
      of grade of malignancy of hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the effectiveness of diffusion-weighted magnetic resonance
      imaging (DWI) in estimating the grade of malignancy of hepatocellular carcinoma.
      MATERIALS AND METHODS: Dynamic contrast-enhanced computed tomography (CE-CT) and
      DWI (b value, 1000 s/mm(2)) were performed on 73 patients. Using DW images, the
      lesions were classified as "visible" or "invisible." The apparent diffusion
      coefficient (ADC) of the lesions was measured. Furthermore, the lesions were
      classified as hypervascular or iso-hypovascular using arterial phase CE-CT
      images. The image findings for each lesion type were compared. RESULTS: The 73
      patients had 98 hepatocellular lesions, of which 12 were histologically diagnosed
      as dysplastic nodules; 39, well-differentiated HCCs; 33, moderately
      differentiated HCCs; and 14, poorly differentiated HCCs. The mean ADC values of
      moderately poorly-differentiated HCCs were significantly lower than well
      differentiated HCCs and dysplastic nodules (P < 0.01). On DW images, >90% of
      moderately (30/33) and poorly differentiated HCCs (13/14) were visible, while 51%
      of well-differentiated HCCs (20/39) and all dysplastic nodules were invisible. Of
      22 iso-hypovascular lesions, 4 were visible on DW images and were poorly
      differentiated HCCs, whereas 18 were invisible and were dysplastic nodules
      (12/18) or well-differentiated HCCs (6/18). CONCLUSION: A combination of
      hypovascularity and visibility on DW images can help distinguish poorly
      differentiated HCCs from low-grade hepatocellular lesions (dysplastic nodules and
      well-differentiated HCCs).

PMID- 19856433
TI  - Resovist enhanced MR imaging of the liver: does quantitative assessment help in
      focal lesion classification and characterization?
AB  - PURPOSE: To improve characterization of focal liver lesions by a prospective
      quantitative analysis of percentage signal intensity change, in dynamic and late
      phases after slow (0.5 mL/s) Resovist administration. MATERIALS AND METHODS:
      Seventy-three patients were submitted on clinical indication to MR examination
      with Resovist. Signal intensity of 92 detected focal lesions (5-80 mm) were
      measured with regions of interest and normalized to paravertebral muscle in
      arterial, portal, equilibrium and T1/T2 late phases, by two observers in
      conference. Five values of percentage variations per patient were obtained and
      statistically evaluated. RESULTS: The enhancement obtained on dynamic study is
      more suitable in hemangiomas and focal nodular hyperplasias than in adenomas and
      hepatocellular carcinomas. To discriminate benign versus malignant lesions on
      late-phase-T2-weighted images, a cutoff = -26%, allowed sensitivity and
      specificity values of 97.4% and 97.7%, respectively. Area under the receiver
      operating characteristic (ROC) curve was 0.99. To differentiate hemangioma versus
      all other focal liver lesions, on late-phase-T1-weighted images, a cutoff = +40%
      permitted sensitivity and specificity values of 90.5% and 98.0%, respectively.
      Area under the ROC curve was 0.98. CONCLUSION: Late phase quantitative evaluation
      after slow Resovist administration, allows to differentiate malignant from benign
      hepatic masses and hemangiomas from all the others focal liver lesions, on T2-/T1
      weighted acquisitions, respectively. J

PMID- 19856434
TI  - Diffusion-weighted MRI: a new tool for the diagnosis of fistula in ano.
AB  - PURPOSE: To retrospectively determine the additional value of diffusion-weighted
      magnetic resonance imaging (MRI) to T2-weighted imaging in the evaluation of anal
      fistulae in comparison with gadolinium (Gd)-enhanced imaging. MATERIALS AND
      METHODS: Thirteen patients (mean age, 35.2 years) with 20 anal fistulae were
      included. The protocol consisted of fat-suppressed T2-weighted fast spin-echo,
      diffusion-weighted single-shot echo-planar (b factors 0 and 800 s/mm(2)), and fat
      suppressed Gd-enhanced T1-weighted gradient echo sequences. Two radiologists
      evaluated images in consensus. RESULTS: Eighteen (90%) fistulae were detected on
      T2-weighted images, and 19 (95%) and 19 (95%) were detected on diffusion-weighted
      and T2-weighted images combined and on Gd-enhanced and T2-weighted images
      combined, respectively. There was no statistically significant difference in
      sensitivity of the techniques (P > 0.5 for all comparison pairs). Confidence
      scores with diffusion-weighted and T2-weighted images combined or those with Gd
      enhanced and T2-weighted images combined were significantly greater than those
      with T2-weighted images alone (P = 0.0047 and 0.014, respectively). CONCLUSION:
      Diffusion-weighted MRI of anal fistulae is a useful sequence and can be a helpful
      adjunct to T2-weighted imaging, especially in patients with risk factors for
      contrast agents.

PMID- 19856435
TI  - Magnetic resonance T2-relaxometry and 2D L-correlated spectroscopy in patients
      with minimal hepatic encephalopathy.
AB  - PURPOSE: To evaluate T(2)-relaxation changes in patients with minimal hepatic
      encephalopathy (MHE) using T(2) relaxometry and to correlate T(2) values with
      brain metabolites evaluated using 2D magnetic resonance spectroscopy (MRS).
      MATERIALS AND METHODS: Eight MHE patients and 13 healthy subjects were evaluated
      using T(2) relaxometry, and eight patients and nine healthy subjects underwent 2D
      MRS in right frontal and left occipital regions. Whole-brain T(2)-relaxation maps
      were compared between MHE and control subjects using analysis-of-covariance, with
      age and gender included as covariates. T(2) values derived from the right frontal
      and left occipital lobes were correlated with the metabolite ratios. RESULTS:
      Multiple brain regions including anterior and mid cingulate cortices, right
      anterior and left posterior insular cortices, right prefrontal, medial frontal,
      and right superior temporal cortices showed significantly increased T(2) values
      in MHE patients compared to control subjects. MRS showed significantly increased
      ratios of glutamine/glutamate (Glx) and decreased ratios of myo-inositol,
      taurine, choline, and myo-inositol/choline (mICh) with respect to creatine (Cr_d)
      in patients compared to controls. Frontal Glx/Cr_d showed significantly positive
      correlation with T(2) values. CONCLUSION: MHE patients showed significantly
      increased T(2) values in multiple brain regions reflecting increased free water
      content and T(2) values in frontal lobe correlated with the increased Glx/Cr_d
      ratio.

PMID- 19856436
TI  - Liver parenchymal enhancement of hepatocyte-phase images in Gd-EOB-DTPA-enhanced
      MR imaging: which biological markers of the liver function affect the
      enhancement?
AB  - PURPOSE: To clarify the factors that predict enhancement of the liver parenchyma
      in hepatocyte-phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid
      (Gd-EOB-DTPA)-enhanced MR imaging. MATERIALS AND METHODS: Gd-EOB-DTPA-enhanced
      hepatocyte-phase MR images of 198 patients with chronic liver diseases (Child
      Pugh class A in 112 patients, class B in 74 patients, and class C in 12 patients)
      were retrospectively analyzed. The hepatocyte-phase images were obtained using
      fat-suppressed T1-weighted gradient-echo images with a 3D acquisition sequence 10
      min and 20 min after IV administration of Gd-EOB-DTPA (0.025 mmol/kg body
      weight). The quantitative liver-spleen contrast ratio (Q-LSC) was calculated
      using the signal intensities of the liver and spleen. Serum albumin levels, total
      bilirubin levels, prothrombin activity, and the results of indocyanine green
      clearance tests (ICGs) were recorded and correlated with the Q-LSC. Logistic
      regression analysis was performed to analyze which factors predict sufficient
      liver enhancement using a Q-LSC of 1.5 as a cutoff value. RESULTS: Only ICGs and
      Child-Pugh classifications showed a statistically significant correlation with
      the Q-LSC. Logistic regression analysis showed that ICGs were the only factors
      that accurately predicted liver enhancement on hepatocyte-phase images.
      CONCLUSION: ICGs were found to be predictors of sufficient liver enhancement on
      hepatocyte-phase images.

PMID- 19856437
TI  - MRI signal intensity based B-spline nonrigid registration for pre- and
      intraoperative imaging during prostate brachytherapy.
AB  - PURPOSE: To apply an intensity-based nonrigid registration algorithm to MRI
      guided prostate brachytherapy clinical data and to assess its accuracy. MATERIALS
      AND METHODS: A nonrigid registration of preoperative MRI to intraoperative MRI
      images was carried out in 16 cases using a Basis-Spline algorithm in a
      retrospective manner. The registration was assessed qualitatively by experts'
      visual inspection and quantitatively by measuring the Dice similarity coefficient
      (DSC) for total gland (TG), central gland (CG), and peripheral zone (PZ), the
      mutual information (MI) metric, and the fiducial registration error (FRE) between
      corresponding anatomical landmarks for both the nonrigid and a rigid registration
      method. RESULTS: All 16 cases were successfully registered in less than 5 min.
      After the nonrigid registration, DSC values for TG, CG, PZ were 0.91, 0.89, 0.79,
      respectively, the MI metric was -0.19 +/- 0.07 and FRE presented a value of 2.3
      +/- 1.8 mm. All the metrics were significantly better than in the case of rigid
      registration, as determined by one-sided t-tests. CONCLUSION: The intensity-based
      nonrigid registration method using clinical data was demonstrated to be feasible
      and showed statistically improved metrics when compare to only rigid
      registration. The method is a valuable tool to integrate pre- and intraoperative
      images for brachytherapy.

PMID- 19856438
TI  - Optimization of the contrast dose and injection rates in whole-body MR
      angiography at 3.0T.
AB  - PURPOSE: To optimize the contrast agent dose and delivery rate used in a novel
      whole-body magnetic resonance angiography (MRA) protocol using a 3.0T MR scanner.
      MATERIALS AND METHODS: Six groups of 20 consenting volunteers underwent whole
      body MRA, with each group receiving a different contrast dose and contrast
      delivery rate. The arterial tree was divided into 16 segments and the image
      quality at each of the anatomical locations, covering the whole body, was
      assessed. Qualitative analysis was carried out using a scoring assessment of
      image quality, and quantitative assessments were performed by measuring contrast
      to-noise (CNR) and a signal-to-noise (SNR) index. RESULTS: Reducing the contrast
      dose from 40 mL to 25 mL was found to significantly increase the CNR in several
      vessels of interest in the arterial tree. There was also a significant increase
      in the qualitative image quality score (P < 0.001). CONCLUSION: This study
      demonstrates that reducing the contrast dose at 3.0T can result in an increase in
      the CNR in the vessels of interest without significantly affecting the SNR.

PMID- 19856439
TI  - Assessment of osteoarthritis in hips with femoroacetabular impingement using
      delayed gadolinium enhanced MRI of cartilage.
AB  - PURPOSE: To determine the feasibility of assessing early osteoarthritis (OA) in
      hips with femoroacetabular impingement (FAI) using delayed Gadolinium enhanced
      MRI of Cartilage (dGEMRIC). MATERIALS AND METHODS: Thirty-seven hips in 30
      patients who had a dGEMRIC scan and radiographic evidence of FAI were identified.
      Clinical symptoms were assessed. Radiographic measurements were performed to
      determine acetabular and femoral morphology. The severity of radiographic OA was
      determined using Tonnis grade and minimum joint space width (JSW). On MRI, the
      alpha angle was measured on the sagittal oblique slices. Correlations between
      dGEMRIC index, patient symptoms, morphologic measurements, radiographic OA, and
      age were determined. RESULTS: Significant correlations were observed between
      dGEMRIC index, pain (P < 0.05), and alpha angle (P < 0.05). The correlation of
      dGEMRIC with alpha angle suggests that hips with more femoral deformity show
      signs of early OA. CONCLUSION: The results of osteoplasty for FAI depend on the
      amount of pre-existing OA in the joint. dGEMRIC may be a useful technique for
      diagnosis and staging of early osteoarthritis in hips with impingement.

PMID- 19856440
TI  - Diffusion-weighted imaging of human carotid artery using 2D single-shot
      interleaved multislice inner volume diffusion-weighted echo planar imaging (2D ss
      IMIV-DWEPI) at 3T: diffusion measurement in atherosclerotic plaque.
AB  - PURPOSE: To determine if 2D single-shot interleaved multislice inner volume
      diffusion-weighted echo planar imaging (ss-IMIV-DWEPI) can be used to obtain
      quantitative diffusion measurements that can assist in the identification of
      plaque components in the cervical carotid artery. MATERIALS AND METHODS: The 2D
      ss-DWEPI sequence was combined with interleaved multislice inner volume region
      localization to obtain diffusion weighted images with 1 mm in-plane resolution
      and 2 mm slice thickness. Eleven subjects, six of whom have carotid plaque, were
      studied with this technique. The apparent diffusion coefficient (ADC) images were
      calculated using DW images with b = 10 s/mm(2) and b = 300 s/mm(2). RESULTS: The
      mean ADC measurement in normal vessel wall of the 11 subjects was 1.28 +/- 0.09 x
      10(-3) mm(2)/s. Six of the 11 subjects had carotid plaque and ADC measurements in
      plaque ranged from 0.29 to 0.87 x 10(-3) mm(2)/s. Of the 11 common carotid artery
      walls studied (33 images), at least partial visualization of the wall was
      obtained in all ADC images, more than 50% visualization in 82% (27/33 images),
      and full visualization in 18% (6/33 images). CONCLUSION: 2D ss-IMIV-DWEPI can
      perform diffusion-weighted carotid magnetic resonance imaging (MRI) in vivo with
      reasonably high spatial resolution (1 x 1 x 2 mm(3)). ADC values of the carotid
      wall and plaque are consistent with similar values obtained from ex vivo
      endarterectomy specimens. The spread in ADC values obtained from plaque indicate
      that this technique could form a basis for plaque component identification in
      conjunction with other MRI/MRA techniques.

PMID- 19856441
TI  - Vessel size imaging using dual contrast agent injections.
AB  - PURPOSE: To investigate the feasibility of a vessel size imaging (VSI) technique
      with separate contrast agent injections for evaluation of the vessel caliber in
      normal tissues and in brain tumors. MATERIALS AND METHODS: Computer simulation
      was first performed to assess the potential errors in the estimation of vessel
      caliber that could result from time shifts between the dual contrast agent
      injections. Eight patients (four female, four male, 37-77 years old) with brain
      tumors (three high-grade gliomas, two low-grade gliomas, and three meningiomas)
      were recruited for clinical study. Dynamic susceptibility contrast magnetic
      resonance imaging (MRI) using gradient echo (GE) and spin echo (SE) echo-planar
      imaging sequences were performed separately with a 10-minute interval on a 3.0T
      scanner. Vessel caliber maps were calculated and analyzed in regions of interest
      at cortical gray matter (GM), thalamus, white matter (WM), and tumors. RESULTS:
      From the computer simulation, the error of vessel caliber measurement was less
      than 8% when the difference between the time-to-peak of the GE and the SE studies
      was 1.5 seconds, and reduced to within 5% when the difference was 1 second. From
      the patient datasets of a 64 x 64 matrix, the estimated vessel calibers were 37.4
      +/- 12.9 microm for cortical gray matter, 20.7 +/- 8.8 microm for thalamus, and
      15.0 +/- 5.1 microm for white matter, comparable to results in the literature.
      Two patients had a VSI with 128 x 128 matrix and showed similar results in vessel
      calibers of normal tissues. All the tumors had larger mean vessel diameter than
      normal-appearing tissues. The difference in vascular size between normal tissue
      and tumor was demonstrated clearly in both the VSIs of regular and high spatial
      resolution. CONCLUSION: This study suggests that VSI with a dual injection method
      is a feasible technique for estimating microvascular calibers of normal tissues
      and brain tumors in clinical scanners.

PMID- 19856442
TI  - Highly accelerated first-pass contrast-enhanced magnetic resonance angiography of
      the peripheral vasculature: comparison of gadofosveset trisodium with
      gadopentetate dimeglumine contrast agents.
AB  - PURPOSE: To investigate the blood pool agent gadofosveset trisodium for first
      pass, dynamic peripheral contrast-enhanced magnetic resonance angiography (pMRA),
      and compare the results with a conventional gadolinium contrast agent. MATERIALS
      AND METHODS: A total of 16 patients were imaged at 1.5T using a prototype
      peripheral vascular coil with high SENSE acceleration. Five received
      gadopentetate dimeglumine ( approximately 0.25 mmol/kg), and 11 received
      gadofosveset trisodium (five standard-dose 0.03 mmol/kg, six high-dose 0.05
      mmol/kg). Quantitative contrast-enhancement and qualitative image quality
      evaluation was compared between agents and doses. RESULTS: High-quality
      diagnostic images were uniformly obtained. The contrast ratio did not
      significantly differ between gadopentetate dimeglumine and high-dose gadofosveset
      trisodium, both of which were greater than standard-dose gadofosveset trisodium.
      High-dose gadofosveset trisodium was equivalent to gadopentetate dimeglumine in
      image quality and subjective vessel-to-background ratio, but significantly better
      for depicting small muscular arteries. Standard-dose gadofosveset trisodium
      showed equivalent image quality and small artery depiction with a slight but
      significant decrease in vessel-to-background ratio as compared to gadopentatate
      dimeglumine. Both gadofosveset trisodium doses trended toward more venous
      enhancement, but this was not a diagnostic problem. CONCLUSION: First-pass
      peripheral CE-MRA using gadofosveset trisodium is feasible, yielding image
      quality comparable to double to triple-dose gadopentetate dimeglumine. Increasing
      the gadofosveset trisodium dose to 0.05 mmol/kg yields further improvements.

PMID- 19856443
TI  - Increased volume of coverage for abdominal contrast-enhanced MR angiography with
      two-dimensional autocalibrating parallel imaging: initial experience at 3.0
      Tesla.
AB  - PURPOSE: To assess the feasibility and the quality of abdominal three-dimensional
      (3D) contrast enhanced MR angiograms acquired at 3.0 Tesla (T) using a new 2D
      accelerated autocalibrating parallel reconstruction method for Cartesian sampling
      (2D-ARC). MATERIALS AND METHODS: With institutional review board approval and
      written informed consent, a prospective trial in 6 normal healthy volunteers and
      23 patients referred for evaluation of suspected renovascular disease was
      performed. The volunteers underwent abdominal MRA with and without 2D-ARC
      acceleration. Images were evaluated independently by two blinded vascular
      radiologists in randomized order. Vessel conspicuity was rated on a five-point
      scale. Evaluation for significant differences between the scores for each
      technique was performed using a Wilcoxon signed-rank test. RESULTS: In the series
      of six volunteers, no statistical significance was found between the image
      quality scores for 2D-ARC accelerated and nonaccelerated exams. A high proportion
      of the 23 clinical 2D-ARC exams were graded as diagnostic (vessel conspicuity
      score >or=2; Reader 1, 96%; Reader 2, 100%) for overall image quality.
      CONCLUSION: Subjective image quality of 2D-ARC accelerated MRA was equivalent to
      the conventional MRA method. However, the 2D-ARC accelerated sequence provided a
      3.5-fold increase in imaging volume, complete abdominal coverage, and a 30%
      reduction in voxel volume, all within the same acquisition time.

PMID- 19856444
TI  - Contrast-enhanced intracranial magnetic resonance angiography with a spherical
      shells trajectory and online gridding reconstruction.
AB  - PURPOSE: To evaluate the feasibility of applying the shells trajectory to single
      phase contrast-enhanced magnetic resonance angiography. MATERIALS AND METHOD:
      Several methods were developed to overcome the challenges of the clinical
      implementation of shells including off-resonance blurring (eg, from lipid
      signal), aliasing artifacts, and long reconstruction times. These methods
      included: 1) variable TR with variable readout length to reduce fat signal and
      off-resonance blurring; 2) variable sampling density to suppress aliasing
      artifacts while minimizing acquisition time penalty; and 3) an online 3D gridding
      algorithm that reconstructed an 8-channel, 240(3) image volume set. Both phantom
      and human studies were performed to establish the initial feasibility of the
      methods. RESULTS: Phantom and human study results demonstrated the effectiveness
      of the proposed methods. Shells with variable TR and readout length further
      suppressed the fat signal compared to the fixed-TR shells acquisition. Reduced
      image aliasing was achieved with minimal scan time penalty when a variable
      sampling density technique was used. The fast online reconstruction algorithm
      completed in 2 minutes at the scanner console, providing a timely image display
      in a clinical setting. CONCLUSION: It was demonstrated that the use of the shells
      trajectory is feasible in a clinical setting to acquire intracranial angiograms
      with high spatial resolution. Preliminary results demonstrate effective venous
      suppression in the cavernous sinuses and jugular vein region.

PMID- 19856445
TI  - Comparison of methods to assess quadriceps muscle volume using magnetic resonance
      imaging.
AB  - PURPOSE: To compare the precision of four methods to estimate the volume of
      quadriceps muscles using axial MRI. MATERIALS AND METHODS: Entire legs of 10
      healthy young subjects were scanned using a 1.5 Tesla magnetic resonance imaging
      scanner and 4-mm-thick sections without any gaps. Quadriceps muscles were
      outlined on all of the slices to obtain the MRI reference standard measure of
      quadriceps muscle volume. This MRI reference standard was compared with the
      volume estimated using (i) the truncated cone formula, (ii) the Cavalieri method,
      (iii) a cubic spline interpolation of missing cross sectional areas, and, (iv)
      the deformation of a parametric specific object. For each method, 3 to 21 slices
      were used. RESULTS: The average volume error was significantly (P < 0.001)
      different in comparing the four methods (4.4%, 2.3%, 1.1%, and 1.2%,
      respectively). In addition, the number of slices required to reach a given volume
      error was significantly (P < 0.001) different across all methods (respectively,
      12, 9, 5, and 7 slices required to reach a volume error of 1.1%). CONCLUSION:
      While methods based on interpolation and deformation of a parametric specific
      object have not been used in literature, these two methods are the most precise
      approaches to reach a given level of precision.

PMID- 19856446
TI  - MR imaging in Duchenne muscular dystrophy: quantification of T1-weighted signal,
      contrast uptake, and the effects of exercise.
AB  - PURPOSE: To quantify the differences between normal and corticosteroid-treated
      Duchenne muscular dystrophy (DMD) lower limb muscle using signal intensity
      measurements on T(1)-weighted and gadolinium contrast-enhanced images and by
      measurement of muscle T(2) values, and to investigate the effect of exercise.
      MATERIALS AND METHODS: Eleven ambulant boys with DMD were imaged at 3 Tesla (T(1)
      weighted, gadolinium enhancement and T(2) measurement) before stepping exercise
      and again (gadolinium, T(2) measurement) 4 days later and were compared with five
      healthy controls imaged 4 days before and after stepping exercise. Muscle region
      of-interest signal intensities were referenced to external oil and gadolinium
      phantoms. RESULTS: DMD thigh muscle T(2) values were significantly higher than
      normal values with the exception of the gracilis muscle. Eight of nine muscles
      studied showed a significant increase in T(1)-w signal intensity in DMD as
      compared to normal muscle, suggestive of increased fat infiltration in DMD
      muscle. In the DMD boys, an exercise effect (increased contrast enhancement) was
      only seen for the tibialis anterior muscle. CONCLUSION: Referenced signal
      intensity measurements may be used to quantify differences between dystrophic and
      normal muscle without T(1) mapping. Stepping exercise does not have a large
      impact on subsequent MR imaging of dystrophic muscle.

PMID- 19856447
TI  - Cross-validation of magnetic resonance elastography and ultrasound-based
      transient elastography: a preliminary phantom study.
AB  - PURPOSE: To cross-validate two recent noninvasive elastographic techniques,
      ultrasound-based transient elastography (UTE) and magnetic resonance elastography
      (MRE). As potential alternatives to liver biopsy, UTE and MRE are undergoing
      clinical investigations for liver fibrosis diagnosis and liver disease management
      around the world. These two techniques use tissue stiffness as a marker for
      disease state and it is important to do a cross-validation study of both
      elastographic techniques to determine the consistency with which the two
      techniques can measure the mechanical properties of materials. MATERIALS AND
      METHODS: In this study, 19 well-characterized phantoms with a range of stiffness
      values were measured by two clinical devices (a Fibroscan and an MRE system based
      respectively on the UTE and MRE techniques) successively with the operators
      double-blinded. RESULTS: Statistical analysis showed that the correlation
      coefficient was r(2) = 0.93 between MRE and UTE, and there was no evidence of a
      systematic difference between them within the range of stiffnesses examined.
      CONCLUSION: These two noninvasive methods, MRE and UTE, provide clinicians with
      important new options for improving patient care regarding liver diseases in
      terms of the diagnosis, prognosis, and monitoring of fibrosis progression, as
      well for evaluating the efficacy of treatment.

PMID- 19856448
TI  - Development and application of magnetic resonance elastography of the normal and
      pathological thyroid gland in vivo.
AB  - PURPOSE: To noninvasively assess the shear stiffness of the thyroid gland in vivo
      in order to determine whether magnetic resonance elastography (MRE) might hold
      clinical utility in the diagnosis of thyroid disease. MATERIALS AND METHODS:
      Quantitative parametric images of thyroid stiffness in normal volunteers and
      patients were produced and quantitative stiffness values measured. Average gland
      stiffness was determined by region of interest analysis of the parametric images.
      This technique was used to assess stiffness of the thyroid in normal individuals
      (n = 12), patients with Hashimoto's thyroiditis (HT; n = 5), and patients with a
      solitary benign (n = 8) or malignant (n = 2) thyroid nodule. RESULTS: Mean shear
      modulus of normal thyroid glands was 1.9 +/- 0.6 kPa at 100 Hz and 1.3 +/- 0.5
      kPa at 80 Hz, while that of HT glands was 2.8 +/- 0.6 kPa and 1.8 +/- 0.6 kPa at
      80 Hz, respectively (P = 0.004 at 100 Hz). Elastographic parameters could not
      differentiate benign from malignant thyroid nodules in these small sample sizes.
      CONCLUSION: We developed a method for the application of MRE to the study of
      thyroid gland pathology. The results show that the HT gland can be differentiated
      from normal thyroid. The clinical utility of this imaging modality in the
      diagnosis and management of thyroid disease awaits further study.

PMID- 19856450
TI  - Measurement of R1 dynamics using sliding window-DESPOT.
AB  - PURPOSE: To measure longitudinal relaxation rate (R1) changes during contrast
      agent studies using a driven equilibrium single pulse observation of T1 (DESPOT)
      method with a sliding window (sw) acquisition. MATERIALS AND METHODS: A sw-DESPOT
      technique was implemented that uses several three-dimensional (3D) image data
      sets to calculate R1 with a temporal resolution of only a single data set.
      Different sources of systematic errors were studied in simulations, and the
      technique was tested in a tumor-bearing mouse using an intravascular contrast
      agent. RESULTS: Consistent concentration distributions of the CA were calculated
      with a temporal resolution of 10 s. CONCLUSION: Sw-DESPOT offers a precise and
      fast method to monitor the CA dynamics in 3D volumes.

PMID- 19856449
TI  - Optimized glutamate detection at 3T.
AB  - PURPOSE: To identify the pulse sequence and acquisition parameters that result in
      the most accurate and repeatable measurements of glutamate (Glu) concentration in
      the brain at 3T. MATERIALS AND METHODS: Simulations were performed to compare the
      accuracy and repeatability of 11 pulse sequences and acquisition parameters,
      within four general classes (PRESS, STEAM, Carr-Purcell PRESS [CPRESS] and TE
      averaged PRESS [JPRESS]), the majority of which were previously suggested as
      optimal for Glu detection. Three of the simulated acquisitions were implemented
      in a clinical scanner and measures of repeatability in vivo were compared to
      their simulated values. RESULTS: Good agreement was demonstrated between
      simulated and experimentally determined measures of repeatability. Among the
      acquisitions considered, a CPRESS sequence with minimal echo time, together with,
      possibly, a short TE PRESS sequence, result in the most repeatable within session
      Glu measurements, while slightly overestimating the Glu concentration. Excellent
      accuracy is demonstrated by the simulations for a JPRESS sequence, at the expense
      of lower repeatability than optimal PRESS or CPRESS sequences. CONCLUSION:
      Further proof of concept is presented toward validation of a simulation approach
      to understand pulse sequence performance in measuring the concentration of a
      given metabolite. Improved within session Glu measurement repeatability is
      predicted for CPRESS and demonstrated in vivo.

PMID- 19856451
TI  - Minimization of Nyquist ghosting for echo-planar imaging at ultra-high fields
      based on a "negative readout gradient" strategy.
AB  - PURPOSE: To improve the traditional Nyquist ghost correction approach in echo
      planar imaging (EPI) at high fields, via schemes based on the reversal of the EPI
      readout gradient polarity for every other volume throughout a functional magnetic
      resonance imaging (fMRI) acquisition train. MATERIALS AND METHODS: An EPI
      sequence in which the readout gradient was inverted every other volume was
      implemented on two ultrahigh-field systems. Phantom images and fMRI data were
      acquired to evaluate ghost intensities and the presence of false-positive blood
      oxygenation level-dependent (BOLD) signal with and without ghost correction.
      Three different algorithms for ghost correction of alternating readout EPI were
      compared. RESULTS: Irrespective of the chosen processing approach, ghosting was
      significantly reduced (up to 70% lower intensity) in both rat brain images
      acquired on a 9.4T animal scanner and human brain images acquired at 7T,
      resulting in a reduction of sources of false-positive activation in fMRI data.
      CONCLUSION: It is concluded that at high B(0) fields, substantial gains in
      Nyquist ghost correction of echo planar time series are possible by alternating
      the readout gradient every other volume.

PMID- 19856452
TI  - Imaging of the walls of saccular cerebral aneurysms with double inversion
      recovery black-blood sequence.
AB  - In this study, we evaluated the wall of saccular cerebral aneurysms (SCAs) using
      two-dimensional double inversion recovery black-blood sequence (BBDI). We
      examined 14 patients with an unruptured SCA (USCA). The BBDI was peripheral-pulse
      gated, and was acquired during the mid-diastolic period. We evaluated whether the
      aneurysmal wall could be visualized with BBDI, and the wall thickness in the neck
      and dome portion of the aneurysm was measured in cases with acceptable imaging
      quality. BBDI demonstrated the USCA walls in ten patients. In four patients, the
      USCA walls were poorly delineated from the adjacent brain parenchyma or
      cerebrospinal fluid. The mean aneurysm size was 8.0 mm. The mean thickness of the
      aneurysmal wall in the neck portion was 0.60 +/- 0.13 mm in 10 cases. The mean
      thickness at the dome portion was 0.46 +/- 0.05 mm in five cases. In this study,
      BBDI revealed some portion of the USCA wall, despite the limited spatial and
      contrast resolution for delineation of the entire USCA wall. In our opinion, this
      technique may be used as an additional imaging tool for the evaluation of the
      aneurysmal wall.

PMID- 19856453
TI  - Regional corpus callosum morphometry: effect of field strength and pulse
      sequence.
AB  - PURPOSE: To investigate whether scanning at different field strengths and pulse
      sequences would influence reproducibility of corpus callosum (CC) morphometric
      measurements as variations in scanning parameters may result in differences in
      contrast properties between resulting images that are independent of the
      underlying tissue but rather reflect the physics of the imaging process.
      MATERIALS AND METHODS: Ten subjects were scanned twice at 3T using magnetization
      prepared rapid gradient-echo imaging (MPRAGE) and modified driven equilibrium
      Fourier transform (MDEFT) sequences and once at 1.5T using MPRAGE. Cross
      sectional area measurements of four callosal regions were performed on
      midsagittal magnetic resonance imaging (MRI) sections. RESULTS: Repeated measures
      analysis of variance with four regions as dependent variables and three scanning
      protocols (1.5T MPRAGE, 3T MPRAGE and 3T MDEFT) as independent variables revealed
      no significant region by protocol interaction: F(6,54) = 0.69, P = 0.52.
      Reliability measures for (3T MPRAGE/3T MDEFT) and (1.5T MPRAGE/3T MPRAGE; 1.5T
      MPRAGE/3T MDEFT) comparisons were high, ranging between 0.90 and 0.97.
      CONCLUSION: Based on our results, combining and comparing CC morphometric data
      obtained at different field strengths and/or with different pulse sequences
      appears possible.

PMID- 19856454
TI  - Volume-targeted and whole-heart coronary magnetic resonance angiography using an
      intravascular contrast agent.
AB  - PURPOSE: To compare volume-targeted and whole-heart coronary magnetic resonance
      angiography (MRA) after the administration of an intravascular contrast agent.
      MATERIALS AND METHODS: Six healthy adult subjects underwent a navigator-gated and
      -corrected (NAV) free breathing volume-targeted cardiac-triggered inversion
      recovery (IR) 3D steady-state free precession (SSFP) coronary MRA sequence (t
      CMRA) (spatial resolution = 1 x 1 x 3 mm(3)) and high spatial resolution IR 3D
      SSFP whole-heart coronary MRA (WH-CMRA) (spatial resolution = 1 x 1 x 2 mm(3))
      after the administration of an intravascular contrast agent B-22956. Subjective
      and objective image quality parameters including maximal visible vessel length,
      vessel sharpness, and visibility of coronary side branches were evaluated for
      both t-CMRA and WH-CMRA. RESULTS: No significant differences (P = NS) in image
      quality were observed between contrast-enhanced t-CMRA and WH-CMRA. However,
      using an intravascular contrast agent, significantly longer vessel segments were
      measured on WH-CMRA vs. t-CMRA (right coronary artery [RCA] 13.5 +/- 0.7 cm vs.
      12.5 +/- 0.2 cm; P < 0.05; and left circumflex coronary artery [LCX] 11.9 +/- 2.2
      cm vs. 6.9 +/- 2.4 cm; P < 0.05). Significantly more side branches (13.3 +/- 1.2
      vs. 8.7 +/- 1.2; P < 0.05) were visible for the left anterior descending coronary
      artery (LAD) on WH-CMRA vs. t-CMRA. Scanning time and navigator efficiency were
      similar for both techniques (t-CMRA: 6.05 min; 49% vs. WH-CMRA: 5.51 min; 54%,
      both P = NS). CONCLUSION: Both WH-CMRA and t-CMRA using SSFP are useful
      techniques for coronary MRA after the injection of an intravascular blood-pool
      agent. However, the vessel conspicuity for high spatial resolution WH-CMRA is not
      inferior to t-CMRA, while visible vessel length and the number of visible smaller
      diameter vessels and side-branches are improved.

PMID- 19856455
TI  - Impact of papillary and trabecular muscles on quantitative analyses of cardiac
      function in hypertrophic cardiomyopathy.
AB  - PURPOSE: To examine the impact of cardiovascular magnetic resonance (CMR)
      partitioning methods on volumetric analysis in hypertrophic cardiomyopathy (HCM)
      patients. The standard CMR method for partitioning ventricular myocardium from
      ventricular cavity includes the myocardial papillary and trabecular muscles in
      the cavity volume. This approach may misrepresent ventricular mass and volume in
      patients with HCM due to large papillary muscles and extensive trabeculations.
      MATERIALS AND METHODS: Ventricular volume and mass analyses were performed in 30
      patients with HCM using the standard method and a detailed method that excluded
      papillary and trabecular muscles from the left ventricular (LV) volume while
      including them in LV mass. We also analyzed the degree of mitral regurgitation
      and compared the results with Doppler echocardiography in a subgroup of 12
      patients. Interobserver variability was assessed. RESULTS: The detailed method
      yielded 17% higher indexed LV mass, 20% lower indexed LV diastolic volume, 13%
      higher LV ejection fraction (EF) (all P < 0.0001). The resultant mitral
      regurgitant volumes using the detailed method had less discrepancy with Doppler
      echocardiography results compared with the results from the standard methods.
      Interobserver variability was similar by both methods. CONCLUSION: For patients
      with HCM, a detailed analysis in which the ventricular papillary and trabecular
      muscles are excluded from LV volume is preferred.

PMID- 19856456
TI  - Effect of contrast media on single-shot echo planar imaging: implications for
      abdominal diffusion imaging.
AB  - PURPOSE: The goal of this study was to determine the effect of contrast media on
      the signal behavior of single-shot echo planar imaging (ssEPI) used for abdominal
      diffusion imaging. MATERIALS AND METHODS: The signal of an ssEPI spin echo
      sequence in a water phantom with varying concentrations of gadolinium was modeled
      with Bloch equations and the predicted behavior validated on a phantom at 1.5T.
      Six volunteers were given gadolinium contrast and signal intensity (SI) time
      courses for regions of interest (ROIs) in the liver, pancreas, spleen, renal
      cortex, and medulla were analyzed. Student's t-test was used to compare
      precontrast SI to 0, 1, 4, 5, 10, and 13 minutes following contrast. RESULTS: The
      results show that following contrast ssEPI SI goes through a nadir, recovering
      differently for each organ. Maximal contrast-related signal losses relative to
      precontrast signal are 20%, 20%, 53%, and 67% for the liver, pancreas, renal
      cortex, and medulla, respectively. The SIs remain statistically below the
      precontrast values for 5, 4, and 1 minute for the pancreas, liver, and spleen,
      and for all times measured for the renal cortex and medulla. CONCLUSION:
      Abdominal diffusion imaging should be performed prior to contrast due to adverse
      effects on the signal in ssEPI.

PMID- 19856457
TI  - T1 independent, T2* corrected MRI with accurate spectral modeling for
      quantification of fat: validation in a fat-water-SPIO phantom.
AB  - PURPOSE: To validate a T(1)-independent, T(2)*-corrected fat quantification
      technique that uses accurate spectral modeling of fat using a homogeneous fat
      water-SPIO phantom over physiologically expected ranges of fat percentage and
      T(2)* decay in the presence of iron overload. MATERIALS AND METHODS: A
      homogeneous gel phantom consisting of vials with known fat-fractions and iron
      concentrations is described. Fat-fraction imaging was performed using a multiecho
      chemical shift-based fat-water separation method (IDEAL), and various
      reconstructions were performed to determine the impact of T(2)* correction and
      accurate spectral modeling. Conventional two-point Dixon (in-phase/out-of-phase)
      imaging and MR spectroscopy were performed for comparison with known fat
      fractions. RESULTS: The best agreement with known fat-fractions over the full
      range of iron concentrations was found when T(2)* correction and accurate
      spectral modeling were used. Conventional two-point Dixon imaging grossly
      underestimated fat-fraction for all T(2)* values, but particularly at higher iron
      concentrations. CONCLUSION: This work demonstrates the necessity of T(2)*
      correction and accurate spectral modeling of fat to accurately quantify fat using
      MRI.

PMID- 19856458
TI  - Personal exposure to static and time-varying magnetic fields during MRI system
      test procedures.
AB  - PURPOSE: To assess personal time-weighted average (TWA) static magnetic field and
      time-varying magnetic field exposure for several system testing tasks routinely
      conducted by engineers at an MRI manufacturing plant. MATERIALS AND METHODS:
      Personal exposure was measured using a personal dosimeter that measured B and
      dB/dt in all three orthogonal directions with a 1 Hz frequency. TWA exposure was
      calculated and random effects and linear mixed effects models were used to assess
      exposure levels and variability. RESULTS: Whereas full-body peak (2T) and TWA
      (200 mT/8 h) exposure limits for the static magnetic field originally proposed by
      ICNIRP were not exceeded, time-varying magnetic field peaks (dB/dt) did exceed
      the proposed threshold value (767.9 mT/s) suggested by IEEE on several occasions
      at the 3.0 Tesla (T) whole-body cylindrical system. CONCLUSION: TWA exposure
      levels are well below the proposed limit values, but peak exposure limits are
      exceeded during certain procedures performed on 1.0T to 3.0T systems.

PMID- 19856461
TI  - ''They can always hurt you more'' bivalirudin and the dynamic balance between
      bleeding and clotting.

PMID- 19856462
TI  - A thriller with a happy end.

PMID- 19856460
TI  - Effective approach for calculations of absolute stability of proteins using
      focused dielectric constants.
AB  - The ability to predict the absolute stability of proteins based on their
      corresponding sequence and structure is a problem of great fundamental and
      practical importance. In this work, we report an extensive, refinement and
      validation of our recent approach (Roca et al., FEBS Lett 2007;581:2065-2071) for
      predicting absolute values of protein stability DeltaG(fold). This approach
      employs the semimacroscopic protein dipole Langevin dipole method in its linear
      response approximation version (PDLD/S-LRA) while using the best fitted values of
      the dielectric constants epsilon'(p) and epsilon'(eff) for the self energy and
      charge-charge interactions, respectively. The method is validated on a diverse
      set of 45 proteins. It is found that the best fitted values of both dielectric
      constants are around 40. However, the self energy of internal residues and the
      charge-charge interactions of Lys have to be treated with care, using a somewhat
      lower values of epsilon'(p) and epsilon'(eff). The predictions of DeltaG(fold)
      reported here, have an average error of only 1.8 kcal/mole compared to the
      observed values, making our method very promising for estimating protein
      stability. It also provides valuable insight into the complex electrostatic
      phenomena taking place in folded proteins.

PMID- 19856463
TI  - Legs bend: why dynamic angiography is important.

PMID- 19856464
TI  - Influence of the HCV subtype on the virological response to pegylated interferon
      and ribavirin therapy.
AB  - The hepatitis C virus genotype is considered to be the most important baseline
      predictor of a sustained virological response in patients with chronic hepatitis
      C treated with pegylated interferon and ribavirin. The influence of the subtype
      on the sustained virological response was investigated in patients infected with
      genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic
      hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The
      overall rate of sustained virological response in the 597 patients was 37.8%.
      Univariate analysis indicated that the sustained virological response of patients
      infected with subtype 1b (39%) tended to be higher than that of patients infected
      with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected
      with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis
      indicated that five factors were independently associated with sustained
      virological response: the age (OR 0.97; 95% CI = 0.95-0.99), absence of cirrhosis
      (OR: 2.92; 95% CI = 1.7-5.0; P < 0.01), absence of HIV co-infection (OR: 2.08;
      95% CI = 1.2-3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74;
      95% CI = 1.2-2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0-2.5; P =
      0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1-3.8; P = 0.03). In
      conclusion, among difficult-to-treat genotypes, the subtype 1a is associated with
      a lower response to anti-HCV therapy than subtypes 1b, 4a, and 4d.

PMID- 19856465
TI  - Co-receptor switch during HAART is independent of virological success.
AB  - The influence of antiretroviral therapy on co-receptor tropism remains
      controversial. To verify if co-receptor tropism shift was affected by HAART, the
      evolution of proviral DNA V3 genotype after 12 months of a new antiretroviral
      regimen was compared between responder and non-responder patients. Baseline blood
      samples were collected from 36 patients infected with HIV-1 subtype-B (18 naive
      and 18 experienced) for virus isolation and env V3 genotyping from plasma HIV-1
      RNA and PBMC DNA. DNA V3 genotyping was repeated after 12 months from initiating
      HAART. WebPSSM was used for categorizing V3 sequences into X4 or R5; for analysis
      purposes, dual/mixed viruses were considered as X4. From the 10 (28%) patients
      changing their proviral DNA V3 genotype during therapy, six shifted from R5-to-X4
      and four from X4-to-R5. The lack of reaching virological suppression was not
      associated with an X4-to-R5 (P = 0.25) or R5-to-X4 (P = 0.14) shift; time-to
      viral suppression and CD4 increase were similar in both groups. No association
      was found between tropism shift and patient baseline characteristics including
      age, sex, CDC stage, CD4 count, viral load, exposure and length of previous
      HAART, enfuvirtide use in the new regimen, number of reverse transcriptase and
      protease resistance-associated mutations. Conversely, CD4 nadir was correlated to
      emergence of X4 virus in proviral DNA (mean 27.2 +/- 30.6 in R5-to-X4 shifting
      patients vs. 161.6 +/- 150.6 in non-shifting patients, P = 0.02). The occurrence
      of a tropism shift in both directions was independent of HAART use, irrespective
      of its efficacy. The CD4 count nadir was the only baseline characteristic able to
      predict an R5-to-X4 viral shift.

PMID- 19856466
TI  - Epidemiology of herpes zoster and its relationship to varicella in Japan: A 10
      year survey of 48,388 herpes zoster cases in Miyazaki prefecture.
AB  - From 1997 to 2006, a total of 48,388 patients with herpes zoster, ranging from a
      3-month-old girl to a 102-year-old woman, were monitored at the 46 dermatology
      clinics in the Miyazaki Prefecture, which has a population of about 1.2 million.
      The mean herpes zoster incidence was 4.15/1,000 person-years, ranging from 1.96
      to 7.84/1,000 person-years among different age groups, and the herpes zoster
      incidence was significantly higher in females (4.58) than in males (3.67). The
      incidence by age group was 1.96-2.86/1,000 person-years below the age of 50
      years, and it increased to 5.23-7.84/1,000 person-years in persons 50-59 and
      older, with a trough in the ages 30-39, forming the small and large peaks.
      Females showed a significantly higher incidence than males, and the difference
      between the sexes was small below age 40 but greater at 40-49, 50-59, and 60-69.
      The incidence of herpes zoster was highest in August and lowest in winter,
      mirroring the prevalence of varicella. The number of herpes zoster cases at 60
      years and older increased more than in the population from 1997 to 2006, and this
      increased incidence of herpes zoster in the 60-69 years and older, especially in
      females, might have raised the rate in contrast to the stable incidence below the
      age of 60 years. This large-scale survey clarifies the epidemiology of herpes
      zoster by age, gender, and season in relation to the prevalence of varicella in
      the Miyazaki Prefecture in Japan.

PMID- 19856467
TI  - Prevalence of human papillomaviruses in urine samples of male patients infected
      with HIV-1 in Sao Paulo, Brazil.
AB  - Human papillomavirus is a DNA virus that includes 118 genotypes. HPV16 is
      responsible for 80% of cervical cancer in women. Men are important reservoirs and
      major transmitters of HPV to their partners. The aim of this study was to detect
      HPV DNA and to determine the prevalence of HPV types 6, 11, 16, and 18 in urine
      samples of men infected with HIV-1. This study included 223 patients infected
      with HIV-1 from the Center of Reference on HIV/AIDS (CRT-SP) and an outpatient
      clinic of HIV. Urine samples were collected and after DNA extraction real-time
      PCR was performed for detection of HPV DNA. Positive samples were then tested by
      conventional PCR using type-specific primers for the four HPV types. A total of
      223 men infected with HIV-1 were tested, 81% of whom were on HAART. Four (5.8%)
      were positive for HPV6, 18 (26.1%) were positive for HPV11, 22 (31.9%) were
      positive for HPV16 and five (7.2%) were positive for HPV18 by conventional PCR.
      Twenty (29%) patients had other HPV types and five patients (1.5%) had multiple
      types. The mean T CD4+cells count was 517 and 441 cells/mm(3) (P = 0.30), in HPV
      negative and positive men, respectively. The HIV viral load was higher in the HPV
      negative group than for in the men with HPV (P = 0.0002). A 30.9% prevalence of
      HPV was found in asymptomatic urine samples of men infected with HIV-1. This
      study suggests that urine may be a useful specimen for HPV screening.

PMID- 19856468
TI  - Viral causes of influenza-like illness: Insight from a study during the winters
      2004-2007.
AB  - Limited information is available on the viral etiology of influenza-like illness
      in southern European countries, and it is still a matter of debate whether
      certain symptoms can be used to distinguish among the specific viruses that cause
      influenza-like illness. The main objective of the present study was to identify
      the demographic and clinical predictors of influenza-like illness due to specific
      viral agents. The study, which was observational in design, was conducted in Rome
      and Naples, Italy. Cases of influenza-like illness were defined as individuals
      with fever >37.5 degrees C and at least one systemic and one respiratory symptom,
      recruited during the winters of 2004-2005, 2005-2006, and 2006-2007. Influenza
      and other respiratory viruses were identified using the polymerase chain reaction
      (PCR), performed on throat swabs. Basic individual information was collected
      using a standard form. A total of 580 persons were included in the analysis.
      Viral pathogens were identified in fewer than 50% of the cases. Overall, 240
      viral agents were detected: 22.8% were positive for influenza viruses, 10.9% for
      adenoviruses, 6.0% for parainfluenza viruses, and 1.7% for respiratory syncytial
      virus. The month of diagnosis, and muscle and joint pain were associated with
      influenza virus, though the positive predictive value (PPV) was low. Abdominal
      pain was associated with adenovirus infection. Although the PPV of symptoms for
      influenza virus infection was low, especially in low activity periods, these
      findings may help clinicians to improve their ability to perform diagnoses.

PMID- 19856469
TI  - Respiratory syncytial virus infection facilitates acute colonization of
      Pseudomonas aeruginosa in mice.
AB  - Pseudomonas aeruginosa causes opportunistic infections in immunocompromised
      individuals and patients ventilated mechanically and is the major pathogen in
      patients with cystic fibrosis, in which it causes chronic infections.
      Epidemiological, in vitro and animal data suggest a role for respiratory virus
      infections in facilitating colonization and infection with P. aeruginosa. A study
      was undertaken to determine whether respiratory syncytial virus (RSV) infection
      could facilitate the initiation of an acute infection with P. aeruginosa in vivo.
      Balb/c mice were infected intranasally with P. aeruginosa, with and without
      simultaneous inoculation with RSV. Lung function measurements were undertaken
      using Whole Body Plethysmography and lungs were harvested 24 hr after
      inoculation. Mice exposed to RSV and P. aeruginosa showed 2,000 times higher
      colony-forming units (CFU) counts of P. aeruginosa in the lung homogenates when
      compared to mice which were only infected with P. aeruginosa and lung function
      changes were more severe in co-infected mice. Control mice receiving RSV alone
      showed no significant changes in lung function or cytokine production, and no
      inflammatory changes in the lung parenchyma. These results suggest that RSV can
      facilitate the initiation of acute P. aeruginosa infection without the RSV
      infection being clinically apparent. This could have implications for treatment
      strategies to prevent opportunistic P. aeruginosa lung infection.

PMID- 19856470
TI  - Application of a modified loop-mediated isothermal amplification kit for
      detecting Norovirus genogroups I and II.
AB  - Norovirus is a major etiologic agent in worldwide outbreaks of gastroenteritis
      associated with food as well as person-to-person transmission. The ubiquitous
      nature of Norovirus necessitates simple and rapid detection methods with high
      accuracy and sensitivity. To this end, several investigators have evaluated the
      usefulness of commercial reverse-transcription loop-mediated isothermal
      amplification (RT-LAMP) kits for detecting Norovirus genogroups I (GI) and II
      (GII). In previous studies, the conventional Loopamp kit for Norovirus GII showed
      a relatively high detection rate, while that for Norovirus GI showed a relatively
      low detection rate. In the present study, clinical Norovirus specimens were used
      to compare the detection rate of a modified Loopamp kit for Norovirus GI with the
      rates of the conventional Loopamp kit for Norovirus GI and an "in-house" RT-LAMP
      GI primer set, methods which had a high detection rate. Results from the present
      study showed that the modified Loopamp kit for Norovirus GI had a higher
      detection rate for two viral genotypes (GI.3, GI.11). On comparison with an "in
      house" GII primer set using genotype GII.4 viruses circulating recently, the
      detection rate by the Loopamp kit for Norovirus GII was found to be higher, with
      a 98% detection rate. These results indicate the applicability of the modified
      LAMP kit for GI and the conventional LAMP kit for GII for detection of
      Noroviruses in clinical samples.

PMID- 19856471
TI  - Long-term outcome of hepatitis B and hepatitis C virus co-infection and single
      HBV infection acquired in youth.
AB  - Co-infection with HBV and HCV seems to be associated with more severe liver
      disease in retrospective and cross-sectional studies in adults, but no data are
      available when co-infection is acquired in youth. The long-term outcome of
      infection acquired in youth was assessed in patients co-infected with HBV and HCV
      and in patients with HBV infection only. Twenty-seven patients with HBV and HCV
      co-infection and 27 patients infected with HBV only were enrolled. Seventy-six
      per cent of the patients were treated with alpha-interferon for 1 year. After a
      median follow-up of 23 years, the annual progression rate of fibrosis was 0.07 in
      patients co-infected with HBV and HCV, and in those infected with HBV it was 0.07
      and 0.11 (P < 0.004) for HBe and anti-HBe-positive patients, respectively. In co
      infected patients, the development of cirrhosis was observed in 2 (7.4%) and of
      hepatocellular carcinoma (HCC) in 1 (3.7%), while in those with HBV, cirrhosis
      appeared in one patient (3.7%). Alcohol intake (OR = 9.5 +/- 1.2; 95% CI = 6.6
      13.9; P < 0.0001) was independently associated with cirrhosis and HCC. alpha
      interferon showed no efficacy during treatment, but the treated group showed
      higher HCV RNA clearance during post-treatment follow-up. Co-infection with HBV
      and HCV and single HBV infection acquired in youth showed a low rate of
      progression to liver fibrosis, no liver failure, and low development of HCC
      during a median follow-up of 23 years (range 17-40).

PMID- 19856472
TI  - Genetic characterization of G3 rotaviruses detected in Italian children in the
      years 1993-2005.
AB  - In recent years an apparent increase in the frequency of detection of G3P[8]
      rotaviruses has been observed worldwide. Similarly, in Italy G3P[8] strains have
      been detected sporadically and in a scattered fashion over 20 years, whereas in
      2003 and 2005 G3P[8] rotavirus activity increased markedly. By analysis of the
      VP7, VP4, VP6, and NSP4 genes of a selection of G3P[8] rotaviruses detected
      between 1993 and 2005, a remarkable sequence conservation was observed in the
      VP7, VP4, and VP6 genes. By converse, after 2002 the Italian G3P[8] strains were
      found to possess unique mutations in significant regions of the NSP4 protein.

PMID- 19856473
TI  - Application of an allele-specific PCR to clinical HIV genotyping samples detects
      additional K103N mutations in both therapy naive and experienced patients.
AB  - Low-level drug resistance is not detected by routine consensus sequence genotype
      analysis (CSA) but low levels of specific mutations, such as the non-nucleoside
      reverse transcriptase inhibitor (NNRTI)-resistant mutation K103N, can be
      quantitated by allele-specific PCR (ASP). This study has applied an ASP to
      quantitate low-level K103N in patients presenting for clinical HIV genotyping and
      assess the correlation with antiretroviral treatment history and outcomes. HIV
      RNA was extracted from patient plasma and subjected to PCR amplification of the
      reverse transcriptase (RT) region followed by genotyping by CSA and real-time ASP
      for K103N. When applied to samples from patients presenting for genotyping, the
      ASP detects K103N, not K103 nor K103R, but cross-reacts with K103S. ASP
      identified all samples that were K103N by CSA (10.5%) and an additional 14% by
      ASP only, representing patients who were therapy naive and with NNRTI treatment
      history. ASP detected therapy-acquired K103N at low levels up to 6 years after
      cessation of NNRTI therapy. In three patients with new HIV diagnosis and K103N
      detected by ASP only, K103N virus declined rapidly from the circulation but
      persisted in PBMC DNA at >12 months post-diagnosis. Efavirenz (EFV) combination
      therapy in three patients with low-level K103N suppressed successfully viral
      load, although one patient developed failure and CSA-detectable K103N after 15
      months of therapy. Thus, analysis of K103N by ASP in conjunction with CSA
      genotyping provides additional information that reflects K103N transmission and
      persistence but detection of low-level K103N does not preclude successful EFV
      containing combination therapy.

PMID- 19856475
TI  - Comparison of the performance of rapid HIV tests using samples collected for
      surveillance in Mozambique.
AB  - Mozambique had low HIV prevalence until the mid-1990s, but recent data indicate
      increasing rates. There is little information on HIV-2. Therefore, HIV
      seroprevalence was assessed among pregnant women and field-ready HIV diagnostic
      strategies were evaluated. A total of 6,930 samples collected by three health
      centers from 2002 to 2005 were tested on site by nurses with two simple/rapid
      tests, Determine HIV-1/2 (Abbott Laboratories; screening) and Uni-Gold HIV
      (Trinity Biotech; confirmation), which is the national HIV testing strategy. The
      prevalence of HIV was 14.0% (2002), 17.8% (2003), 16.5% (2004), and 20.2% (2005).
      A subset of 888 samples collected 2003 was sent to the Central Microbiology
      Laboratory, Maputo for evaluation of tests and testing strategies. The assays
      included for comparison were Capillus HIV-1/HIV-2 (Trinity Biotech),
      DoubleCheckGold HIV-1&2 (Orgenics) and Enzygnost Anti-HIV-1/2 Plus (Behringwerke,
      reference ELISA). Confirmation of reactive samples was done by Uni-Gold HIV and
      ImmunoComb II HIV-1&2 BiSpot (for HIV type differentiation). The Capillus HIV-1/
      HIV-2 + ImmunoComb II HIV-1&2 BiSpot combination was the gold standard. The
      sensitivity of the rapid/simple screening assays (Determine HIV-1/2,
      DoubleCheckGold HIV-1&2) was 100% (N = 160) and their (initial) specificities
      were 99.6% and 99.7%, respectively. Repeated testing and combinations of assays
      increased the specificity. Four suspected cases of recent seroconversion were
      found. Together with the increasing prevalence rates, this may indicate that
      Mozambique is a high-incidence area, although further studies are needed to
      confirm this. Testing strategies for on-site screening and confirmation based on
      the combination of Determine HIV-1/2, Uni-Gold HIV and DoubleCheckGold HIV-1&2
      are well suited for local field use.

PMID- 19856474
TI  - Rapid changes in rotaviral genotypes in Ecuador.
AB  - Previous studies suggest that the emerging G9P[8] genotype was the most prevalent
      rotavirus genotype in Ecuador during 2005. This present study provides a temporal
      analysis of the distribution of rotavirus genotypes in two locations within
      Ecuador by adding additional years (2006 - early 2008) to the originally reported
      2005 data. Data were collected in a rural (northern coastal Ecuador) and urban
      (Quito) area. In the rural area, a community sample of cases (those presenting
      diarrhea) and controls (those not presenting diarrhea) were collected between
      August 2003 and March 2008 resulting in a total of 3,300 stool samples (876 cases
      and 2,424 controls). Of these samples, 260 were positive for rotavirus by an
      immunochromatographic test (196 cases and 64 controls). In Quito, 59 fecal
      samples were collected from children presenting diarrhea and diagnosed with
      rotavirus. An RT-PCR analysis of samples collected between 2005 and 2007
      suggested that G9 was replaced by G1 and G2 in the rural and urban settings.
      During this period G9 decreased from 79% to 9% while G2 increased from 0% to 43%
      in the rural communities, and G9 decreased from 79% to 37% while G2 increased
      from 3% to 57% in the urban area of Quito. This rapid replacement of G9 by G1 and
      G2 reinforces the necessity of surveillance to inform vaccination programs.

PMID- 19856476
TI  - Serum KL-6 levels as a biomarker of lung injury in respiratory syncytial virus
      bronchiolitis.
AB  - To evaluate whether KL-6 concentration is a useful biomarker of the severity of
      respiratory syncytial virus (RSV) bronchiolitis, we determined KL-6
      concentrations in patients with RSV bronchiolitis with or without chronic heart
      disease (CHD). We enrolled 52 patients who had been diagnosed with RSV
      bronchiolitis and required admission to the hospital at the Department of
      Pediatrics of Fukushima Medical University School of Medicine from 2004 to 2005.
      These patients were divided into two groups: Group 1 consisted of patients
      without any underlying disease, and Group 2 consisted of patients with CHD. These
      patients were assigned to three categories. Stage A consisted of patients without
      oxygen dosage, stage B of patients who required oxygen dosage, and stage C of
      patients required artificial respiration. We evaluated baseline characteristics,
      clinical features, and serum KL-6 concentration in Group 1, Group 2, and a
      control group (healthy infants without infection). Mean serum KL-6 concentrations
      in patients with RSV bronchiolitis were higher than those in the control group
      (471.8 +/- 236.9 and 127.1 +/- 69.1 U/ml, respectively). Mean serum KL-6
      concentration was higher in Group 2 than in Group 1 (692.8 +/- 313.1 and 390.4 +/
      132.7 U/ml, respectively). Mean serum KL-6 concentrations were higher in stage C
      than in stages A and B, and mean serum KL-6 concentrations were higher in stage B
      than in stage A. These findings suggest that serum KL-6 is associated with the
      severity of RSV bronchiolitis and that it may be a useful biomarker for the
      severity of RSV bronchiolitis.

PMID- 19856477
TI  - Evolving clinical landscape of chronic hepatitis B: A multicenter Italian study.
AB  - The aim of the study was to evaluate the characteristics of chronic hepatitis B
      with special reference to the geographical origin of the patients and to the
      prevalence of HBeAg and viral and non-viral co-factors of liver disease. A cross
      sectional multicenter survey was undertaken, which enrolled 1,386 HBsAg chronic
      carriers observed consecutively in 21 referral centers over a 6-month period. The
      prevalence of HBeAg in patients was 11%; the presence of HBeAg was associated
      independently with a younger age and co-infection with HIV. Anti-HDV, anti-HCV,
      or anti-HIV antibodies were detected in 8.1%, 6.5%, and 2%, respectively.
      However, among the patients first diagnosed during the study period (incident
      cases), 14.3% were anti-HDV positive. Seven percent of the patients were
      immigrants; they were younger than Italian patients and 18% were HBeAg positive;
      no difference was observed in the prevalence of anti-HDV, anti-HCV, or anti-HIV
      antibodies. The presence of cirrhosis was associated independently with an age
      >52 years, the presence of anti-HDV or anti-HCV, alcohol use >4 drinks/day, and a
      high BMI. The clinical epidemiology of chronic hepatitis B virus (HBV) infection
      shows a dynamic profile, with the potential for re-emergence of cases with HBeAg
      or anti-HDV and an emerging impact of metabolic factors on the evolution of liver
      disease.

PMID- 19856478
TI  - Co-circulation of three pathogenic hantaviruses: Puumala, Dobrava, and Saaremaa
      in Hungary.
AB  - Hantaviruses (Bunyaviridae) cause hemorrhagic fever with renal syndrome (HFRS) in
      Eurasia and hantavirus (cardio)pulmonary syndrome (HCPS) in the Americas. HFRS is
      caused by Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV),
      Saaremaa virus (SAAV), and Puumala virus (PUUV). Of those, only HTNV is not
      present in Europe. In recent years, hantaviruses, described in other parts of
      Europe, were also detected at various locations in Hungary. To study the genetic
      properties of Hungarian hantaviruses in detail, sequences of the viral S and M
      segments were recovered from bank voles (Myodes glareolus), yellow-necked mice
      (Apodemus flavicollis), and striped field mice (Apodemus agrarius) trapped in the
      Transdanubian region. As expected, the sequences recovered belonged,
      respectively, to PUUV (two strains), DOBV (one strain), and SAAV (one strain). On
      phylogenetic trees two new Hungarian PUUV strains located within the well-
      supported Alpe-Adrian (ALAD) genetic lineage that included also Austrian,
      Slovenian, and Croatian strains. Analysis of the Hungarian SAAV and DOBV genetic
      variants showed host-specific clustering and also geographical clustering within
      each of these hantavirus species. Hungarian SAAV and DOBV strains were related
      most closely to strains from Slovenia (Prekmurje region). This study confirms
      that multiple hantaviruses can co-circulate in the same locality and can be
      maintained side-by-side in different rodent species.

PMID- 19856479
TI  - Intrahepatic long-term persistence of parvovirus B19 and its role in chronic
      viral hepatitis.
AB  - Parvovirus B19 (B19V) has been detected in the liver of Asian patients infected
      with HBV and may contribute to acute and chronic liver disease. This study aimed
      to investigate the impact of B19V infection in European patients with viral
      hepatitis. B19V DNA was detected in 1/91 and 0/50 serum samples from patients
      with chronic hepatitis C and B, respectively. In contrast, B19V DNA was amplified
      frequently from explanted end-stage liver tissues (37/50, 74%) and from routine
      biopsy samples (14/32, 44%) (P < 0.05). However, there was no significant
      difference in B19V copy number per cell between these two groups. B19V-specific
      CD4(+) T-cell responses to two dominant MHC-class-restricted epitopes were
      detected in a similar frequency in healthy anti-B19V-positive individuals (3/19;
      16%) and patients with chronic hepatitis C (3/13; 23%). These results indicate
      that B19V can persist in the liver. However, there is no evidence that B19V is a
      "hepatitis virus" worsening liver disease in European patients with chronic
      hepatitis C.

PMID- 19856480
TI  - Prevalence of different HPV types and estimation of prognostic risk factors based
      on the linear array HPV genotyping test.
AB  - The aim of the study was to evaluate the prevalence and risk factors of HPV in a
      gynecologic population attending outpatient clinics using two new molecular
      tests. The Amplicor HPV test and the Linear Array (LA) HPV Genotyping test were
      used for the detection of HPV DNA in 320 women. Multiple logistic regression was
      used to identify independent prognostic factors of HPV positivity. The agreement
      between the two methods in terms of their qualitative results was 89.3% (kappa:
      0.63). Based on the LA results, the overall prevalence of HPV DNA was 49.1%, 95%
      confidence interval (95% CI: 43.5%, 54.7%). The prevalence of high-risk HPV types
      was 30.3%. The predominant types were HPV-6 (24.8%) and HPV-16 (20.4%). Among
      women with normal cytology, the prevalence of HPV was much higher in those
      presenting other findings, such as inflammation, than those without other
      abnormal findings (49.5% vs. 31.5%). On the basis of multivariate analysis, the
      risk of HPV infection was higher among women with multiple sexual partners [>3
      vs. 1: OR = 3.1, 95% CI: (1.5, 7.2)], Pap smear findings [low/high-grade lesions
      vs. negative: OR = 2.8, 95% CI: (1.2, 6.5)], the presence of warts [yes vs. no:
      OR = 3.0, 95% CI: (1.5, 6.3)] and no history of child birth [no vs. yes: OR =
      2.6, 95% CI: (1.0, 6.7)]. Younger age was an additional risk factor for HPV
      infection with carcinogenic genotypes [OR for 1 year increase = 0.93, 95% CI:
      (0.89, 0.98)].

PMID- 19856481
TI  - NS5A(ISDR-V3) region genetic variability of Tunisian HCV-1b strains: Correlation
      with the response to the combined interferon/ribavirin therapy.
AB  - In the non-structural protein 5A (NS5A) of hepatitis C virus (HCV), mutations
      within the interferon sensitivity-determining region (ISDR), the PKR-binding
      domain (PKR-BD), the variable region 3 (V3), and the interferon/ribavirin
      resistance-determining region (IRRDR) have been correlated with the IFN-based
      therapy response. In Tunisia, where a high prevalence of HCV-1b has been found,
      no data regarding the implication of NS5A in treatment response were available.
      The current study examined the relationship between the pre-treatment mutation
      number within ISDR, PKR-BD, V3, IRRDR, as well as in the entire ISDR-V3 region of
      NS5A (aa 2209-2379) and the response to the 48-week course of combined IFN plus
      ribavirin therapy in 15 HCV-1b-infected Tunisian patients. Referring to HCV-J
      sequence, a significant high genetic variability was observed within PKR-BD in
      the sustained virological responder patients compared to non-responders (P =
      0.040). More importantly, when considering the entire region from ISDR to V3,
      referred to as NS5A(ISDR-V3), a clear difference in the mutation number was
      observed between sustained virological responders (19.6 +/- 3.16) and non
      responders (15.0 +/- 1.41) (P = 0.002). Additionally, a more detailed analysis of
      NS5A(ISDR-V3) region revealed an elevated degree of mutation rate within the
      region located between amino acids 2282 and 2308 (P = 0.0006). Interestingly, an
      analysis of specific amino acid variations defined proline and serine at position
      2300 as signature patterns for sensitive and resistant strains, respectively. The
      genetic variability within the NS5A region of HCV-1b strains was associated with
      the response to the combined IFN plus ribavirin therapy in our Tunisian cohort.

PMID- 19856482
TI  - A validated spectrophotometric method for quantification of prenylated flavanones
      in pacific propolis from Taiwan.
AB  - INTRODUCTION: Because of its chemical diversity, the only way to standardise
      propolis is to specify multiple standards for different propolis types according
      to the corresponding chemical profile. So far, this has been done only for
      European propolis. OBJECTIVE: To develop a rapid low-cost spectrophotometric
      procedure for quantification of bioactive prenylated flavanones in Taiwanese
      propolis. METHODOLOGY: The proposed method quantifies the total flavanones on the
      basis of their absorption as coloured phenylhydrazones formed by interaction with
      2,4-dinitrophenylhydrazine. The procedure was validated through model mixture of
      compounds representing the composition of Taiwanese propolis according to
      previous studies. The major flavanones of the propolis samples (propolins C, D, F
      and G) were quantified by HPLC. Antiradical activity against DPPH was also
      measured. The DNP (dinitrophenylhydrazine) spectrophotometric method is applied
      for the first time for quantification of prenylated flavanones. RESULTS:
      Spectophotometric procedure applicable to new type propolis (Macaranga type) was
      developed with recovery between 105 and 110% at the concentration range of 0.573
      1.791 mg/mL. Six propolis samples were analysed by spectrophotometry using the
      procedure developed and validated, and by HPLC as the results demonstrated
      satisfactory agreement. Neither the spectrophotometric data nor the values
      measured by HPLC showed significant correlation with the antiradical activity
      against DPPH. CONCLUSION: The proposed spectrophotometric procedure is useful for
      routine analyses of Macaranga-type propolis, because of its simplicity,
      repeatability and acceptable accuracy. Its application to a number of commercial
      samples could be used as a basis for standardisation and quality control of
      Pacific propolis.

PMID- 19856483
TI  - Reality check: a comparison of college students and a community sample of mock
      jurors in a simulated sexual violent predator civil commitment.
AB  - Despite concerns about generalizability, past mock trial research has concluded
      that effects of sample (i.e., students versus representative mock jurors) are
      negligible. The current study was conducted to explore this conclusion within the
      conceptual framework of cognitive-experiential self-theory (CEST). Through a mock
      civil commitment hearing of a sexually violent predator, responses of student (n
      = 138) and representative (n = 240) mock jurors were compared. Results revealed
      several important differences between samples: (a) the student sample scored
      higher on the rational processing measure (i.e., need for cognition); (b)
      students' verdicts were also significantly correlated to a measure of their
      cognitive processing style, an enduring personal characteristic related to the
      extent to which an individual engages in either effortful/effortless cognition;
      and (c) the representative sample was more punitive, was more persuaded by
      clinical expert testimony, and evidenced a greater gender effect in its
      decisions. Implications for jury decision-making research are discussed.

PMID- 19856484
TI  - Pravastatin use and cancer risk: a meta-analysis of individual patient data from
      long-term prospective controlled trials in Japan.
AB  - PURPOSE: To assess the influence of pravastatin therapy on cancer morbidity and
      mortality by a meta-analysis of individual patient data (IPD) from three
      independent Japanese large-scale clinical trials. METHODS: We conducted a meta
      analysis of IPD collected from three large-scale prospective studies, the
      Management of Elevated Cholesterol in the Primary Prevention Group of Adult
      Japanese (MEGA) Study, Kyushu Lipid Intervention Study (KLIS), and Hokuriku Lipid
      Coronary Heart Disease Study-Pravastatin Atherosclerosis Trial (Holicos-PAT),
      which compared cardiovascular outcomes with pravastatin therapy and non-statin
      therapy in Japanese patients with hypercholesterolemia over a follow-up period of
      >or=4 years. The incidence of cancer or cancer death in the pravastatin and non
      statin therapy groups was compared by multivariate Cox proportional hazard models
      stratified by trial. Subgroup analyses by sex and age were also conducted using
      the same methods. RESULTS: In a total of 13 724 patients (mean age, 58 years;
      women, 48%) included in the analyses, pravastatin was not associated with an
      increased risk of developing cancer (hazard ratio [HR], 0.99; 95% confidence
      interval [95%CI], 0.81-1.19). Similarly, pravastatin therapy did not
      statistically affect cancer death (HR, 0.86; 95%CI, 0.61-1.21). Moreover, in
      subgroups analyses, no influence was observed on cancer incidence or death in
      relation to sex and age. CONCLUSION: Pravastatin did not increase the rate of
      cancer incidence or cancer death in a large population of Japanese patients
      followed for >70,000 patient-years.

PMID- 19856485
TI  - SIP 1: Increasing the overall epidemic vaccination coverage. Epidemic vaccination
      coverage: it's a long way to Tipperary!

PMID- 19856486
TI  - SIP 3: Epidemic and pandemic use of antivirals. Antivirals: "You're still the
      one...".

PMID- 19856487
TI  - SIP 5: Social distancing during a pandemic. Not sexy, but sometimes effective:
      social distancing and non-pharmaceutical interventions.

PMID- 19856488
TI  - Stakeholder dialogue, broadening of support and use of communication: an
      integrated and integral part of influenza preparedness.

PMID- 19856489
TI  - Laser photocoagulation and intravitreal injection of triamcinolone for retinal
      vein occlusions.

PMID- 19856491
TI  - [The question bigger than the sum of legal and medical aspects].

PMID- 19856490
TI  - Progressivity and participation: children's management of parental assistance in
      paediatric chronic pain encounters.
AB  - This article examines how older paediatric patients (10-18 years) initiate
      different actions, including the solicitation of parental assistance, to
      accomplish the task of answering clinicians' symptom questions in three
      paediatric tertiary care clinics. Using the qualitative method of conversation
      analysis to examine children's symptom accounts in 69 video-recorded outpatient
      intake visits, I describe four child-initiated strategies that preclude, solicit
      and limit parental assistance in the interactional environment of having
      difficulties in providing an answer. These strategies are: children's own answer
      searches, children's solicitations of corroboration, children's solicitations of
      an answer, and children's answer completions. Supported by the clinicians' strong
      commitment to child-centredness, children manage to solicit parental assistance
      without losing the opportunity to present their own symptom accounts.

PMID- 19856492
TI  - Use of epinephrine autoinjectors for treatment of anaphylaxis: which commercially
      available autoinjector do patients prefer?

PMID- 19856493
TI  - [Tissular and subcellular localization of the ATP synthase B subunit in
      Clonorchis sinensis].
AB  - OBJECTIVE: To illustrate the distribution of ATP synthase b subunit in the tissue
      of Clonorchis sinensis adult and its subcellular mimical localization in HeLa
      cells. METHODS: With the antiserum against recombinant CsATP-synt_B protein
      raised from SD rats as primary antibody, paraffin sections of the adult of C.
      sinensis were processed by the method of fluorescent immunohistochemistry to
      observe the distribution of CsATP-synt_B protein in adult worm. According to the
      prediction by bioinformatics of the definite mitochondrial targeting sequence
      (MTS) and probable Bipartite nuclear localization signals (NLS_BP)in CsATP-syntB
      sequence, recombinant pEGFP-N1 plasmids containing the intact and three defective
      CsATP-synt_B sequence with single defect of MTS or NLS_BP or double defect
      respectively were constructed. The recombinant plasmids and the control plasmid
      pEGFP-N1, pEYFP-Mito and H2B-CFP, were transfected into the HeLa cells by
      Lipofectamine 2000 reagent and the subcellular location of the GFP fusion protein
      was observed with confocal microscopy. RESULTS: The CsATP-synt_B protein appeared
      to distribute all over the adult worm, especially abundant on the acetabulum,
      ovary, vitellarium and tegument. The intact CsATP-synt_B was definitely expressed
      in mitochondria and/or nucleus of infected HeLa cells, whereas the MTS-deleted
      mutant only in cytoplasma and nucleus, the NLS_BP-deleted mutant in mitochondria
      and cytoplasm, and the double defect mutant only in cytoplasm. CONCLUSION: The
      distribution of CsATP-synt_B in adult is accord with that of mitochondria, and
      mainly exits in the organs and the tissues of active energy metabolism. This
      study first predicted and confirmed that CsATP-synt_B can be expressed in the
      nucleus.

PMID- 19856494
TI  - [Comparative proteomic analysis of the promastigotes and amastigotes of
      Leishmania donovani].
AB  - OBJECTIVE: To explore the protein profile and identify developmentally regulated
      proteins of the promastigotes and axenic amastigotes with comparative proteomics
      technique. METHODS: The total proteins of promastigotes and axenic amastigotes of
      Leishmania donovani SC6 strain were separated by two-dimensional electrophoresis
      (2-DE) in a broad pH range (3-10), and the gel was stained with Coomassie blue.
      The images were analyzed by PDQuest 1.0 software, and the major developmentally
      regulated proteins were identified by electrospray mass spectrometry. RESULTS:
      Approximately 700 protein spots were revealed in equivalent proteins of the
      promastigotes and axenic amastigotes separated by 2-DE, among which more than 90%
      protein spots showed equivalent quantity and distribution, with 6 proteins up
      regulated and 3 proteins down-regulated in axenic amastigotes compared with
      promastigotes. Five of the 6 up-regulated proteins were with known function,
      respectively ascribed as Rieske iron-sulfur protein precursor, alpha-tubulin,
      peroxidoxin 1, dihydrolipoamide acetyltransferase precursor, and mannose-1
      phosphate guanylyltransferase. Two of the 3 down-regulated proteins were
      identified as heat shock protein 70 and beta-tubulin. The functions of the
      developmentally regulated proteins were related to the carbohydrate/energy
      metabolism, stress response, or formation of cell membrane/cytoskeleton.
      CONCLUSION: The findings demonstrate the differences in protein expression
      profiles between promastigotes and amastigotes.

PMID- 19856495
TI  - [Heavy infection of Clonorchis sinensis with complication of cholelithiasis].

PMID- 19856496
TI  - [Immunoreactivity of the recombinant protein of Echinococcus granulosus antigen
      B].
AB  - OBJECTIVE: To express the recombinant antigen B (rAgB) of Echinococcus granulosus
      (Eg) and investigate its immunoreactivity. METHODS: The rAgB gene fragments were
      inserted into pET41a (+) prokaryotic vector. The recombinant plasmid was
      transformed into E. coli BL21 (DE3) and followed by expression of the protein
      induced by isopropyl beta-D-1-thiogalactopyranoside (IPTG). The protein was
      purified with sepharose 4B by affinity chromatography, and tested by SDS-PAGE
      electrophoresis. Its immunoreactivity was examined by Western blotting, and a
      rapid diagnosis kit for human echinococcosis was used as control. RESULTS: The
      constructed recombinant plasmid pET41a-rAgB was identified by PCR, digestion with
      restriction enzyme and sequencing. The recombinant rAgB-GST was about Mr 40 800
      with a purity of 78.4%. Western blotting showed that the positive rate of rAgB
      GST reacting with sera of cystic echinococcosis (CE), alveolar echinococcosis
      (AE), paragonimiasis westermani and clonorchiasis sinensis patients, and healthy
      persons is 79.2%(95/120), 51.1% (23/45), 0 (0/32), 0 (0/20), and 0 (0/24),
      respectively. Its overall sensitivity and specificity were 79.2% (95/120) and
      81.0% (98/121), respectively, slightly higher than the sensitivity (72.8%,
      75/103) and specificity (76.9%, 30/39) of the rapid diagnosis kit for human
      echinococcosis. CONCLUSION: The rAgB-GST recombinant protein is recognized by the
      sera of CE and AE patients, showing a proper immunoreactivity.

PMID- 19856497
TI  - [In vitro effect of secnidazole benzoate on Trichomonas vaginalis].
AB  - OBJECTIVE: To research the trichomonacidal effect of secnidazole benzoate in
      vitro. METHODS: Trichomonas vaginalis was cultured in liver extract medium in 96
      well microplate. The culture suspension of Trichomonas vaginalis was divided into
      four groups: secnidazole benzoate, secnidazole, metronidazole and control, with
      medium as blank control. MTT colorimetric assay was applied to determine the
      inhibitory effect of secnidazole benzoate on the proliferation of Trichomonas
      vaginalis. The culture suspension was transferred into test tubes and divided
      into same groups to observe inhibitory effect by the classical microscopic
      counting method. RESULTS: After 24 h incubation, the proliferation of the
      parasites was concentration-dependent by secnidazole benzoate (t = 9.02, P <
      0.01) at the concentration ranges from 0.15 microg/ml to 20.0 microg/ml with a
      relative inhibition rate (%) of 14.6, 28.7, 31.3, 60.4, 89.0, 89.2, 95.6, and
      100.0 for MTT colorimetric assay, and 18.2, 31.1, 39.7, 68.8, 84.6, 90.1, 94.6,
      and 100.0 for counting method, respectively. In the period of 6-24 h incubation,
      the inhibition was in a time-dependent manner. The minimum sterilizing
      concentration and the minimum inhibitory concentration were 20 microg/ml and 0.15
      microg/ml respectively. CONCLUSION: Secnidazole benzoate shows a similar
      trichomonacidal effect to metronidazole and secnidazole.

PMID- 19856498
TI  - [Experimental study on recombinant Bla g 2(rBla g 2) in the treatment of allergic
      asthma in mice].
AB  - OBJECTIVE: To study the therapeutic effect on murine allergic asthma with
      recombinant Bla g 2 (rBla g 2) allergen and its possible mechanism. METHODS:
      Eighteen BALB/C mice were randomly divided into three groups: normal control
      group (group A), asthma model group (group B), and recombinant protein rBlag2
      treatment group (group C). Mice in groups B and C were subcutaneously immunized
      weekly with rBla g 2 (50 mg) formulated in Al (OH)3 adjuvant for three weeks.
      Group A received only adjuvant emulsified with normal saline. Two weeks after the
      last inoculation, mice in group C were administered each with rBla g 2 (100 mg)
      /dose, and groups A and B were given PBS. All the mice received eight doses at 2
      day intervals. One week after the last immunotherapy, mice in groups B and C were
      intranasally challenged with 50 mg rBla g 2 daily for seven days, while mice in
      group A received PBS. Twenty-four hours after the challenge, the following items
      were examined: airway hyperresponsiveness of mice, total cellular score and cell
      classification in bronchoalveolar lavage fluid (BALF), level of rBla g 2-specific
      IgE and IgG2a in serum, lung inflammation by HE stain, and Bcl-2 expression of
      eosinophils of lung by immunohistochemistry. RESULTS: Compared with group B,
      group C showed a decreased Penh value of airway hyperresponsiveness (P < 0.05),
      reduced serum rBla g 2-specific IgE but increased IgG2a (P < 0.01), and reduced
      Bcl-2 expression of eosinophils. Total cells [(24.60 +/- 15.08) x 10(5)/ml] and
      eosinophils [(22.20 +/- 3.76) x 10(5)/ml] in BALF of group B significantly
      increased than those of group C [(14.30 +/- 4.95) x 10(5)/ml and (5.20 +/- 1.56)
      x 10(5)/ml, respectively] (P < 0.01). The interstitial space surrounding the
      airway lumen was characterized by a densely mixed cellular infiltrate, tissue
      edema and epithelium tissue damage in group B, while lung inflammation of group C
      reduced considerably. Each test value of group C was substantially similar to
      that of group A. CONCLUSION: The experiment shows proper immunotherapeutic
      efficacy of rBla g 2 in murine allergic asthma, which may possibly related to the
      apoptosis of eosinophils.

PMID- 19856499
TI  - [Conditional inhibition of hemozoin formation by chloroquine in vitro].
AB  - OBJECTIVE: To study the characteristics of inhibition on hemozoin formation by
      chloroquine under in vitro condition. METHODS: Under different concentrations
      (0.5-2 mol/L) of sodium acetate (NaAc) and at the pH range of 4.0-5.0,
      chloroquine was tested for inhibition of beta-hematin (hemozion) formation by
      using the HPIA (heme polymerization inhibitory activity) assay. The morphology of
      beta-hematin crystals was determined by light microscopy. Ultraviolet
      spectrophotometry was employed to measure beta-hematin content, and the size of
      beta-hematin crystal was analyzed by X-ray diffraction (XRD). RESULTS:
      Chloroquine exhibited varied effect on beta-hematin formation, depending on pH
      value and Na+ concentration. When the NaAc concentration increased from 0.5 mol/L
      (pH 4.2) to 2 mol/L (pH 4.8), the chloroquine inhibitory effect also increased.
      Results suggested that there exists a threshold pH, below which the beta-hematin
      formation escalates and chloroquine inhibition declines, and at or above which
      chloroquine exerts a stronger inhibitory effect on beta-hematin formation. With
      the increase of pH from 4.4 to 4.8, the crystallinity and the size of crystal
      changed from 6.93% and 357 angstrom to 6.32% and 264 angstrom, respectively. When
      pH reached to 5, no more beta-hematin formed. Chloroquine could reduce the
      crystallinity and crystal size of beta-hematin at same pH value. Morphology
      analysis on the samples was consistent with the above results. CONCLUSION:
      Chloroquine inhibits hemozoin formation only when the pH value is at or above
      threshold pH.

PMID- 19856500
TI  - [Establishment and application of school-based health promotion and intervention
      model of schistosomiasis in lake-type endemic area].
AB  - OBJECTIVE: To establish an intervention model of school health promotion, and
      apply it in developing "schistosomiasis-free schools". METHODS: At the pilot
      stage, all students of Henghu primary school and Banshan primary school in
      Xinjian County of Jiangxi Province were selected as experiment group and control
      group, respectively. A baseline survey covered knowledge and attitude on
      schistosomiasis control, water contact behaviors and Schistosoma japonicum
      infection rate. Two health promotion intervention models, i.e. "information
      communication + training of protection skill + reward & punishment" (model A,
      1993-1999) and "information communication + behavior participation +
      encouragement" (model B, 2000-2007), were implemented in Henghu school. The
      effect of two models was compared by infection rate. At the application stage,
      all students of 8 schools in Xinjian County, Nanchang County, and Jinxian County
      were chosen for evaluation of the effectiveness of Model B with same methods and
      index. RESULTS: Before intervention there was no significant statistical
      difference on the passed rate of anti-schistosomiasis knowledge, correct rate of
      anti-schistosomiasis attitude, frequency of infested water exposure and the
      infection rate between Henghu and Banshan schools (P > 0.05). In Henghu school,
      the intervention showed significant effect on the scores of knowledge and
      attitude after one year (P < 0.01), raised from 9.0% and 55.1% before
      intervention to 94.4% and 98.9% after intervention, respectively. The frequency
      of infested water exposure and the infection rate significantly decreased from
      14.6% and 13.5% before intervention to 1.9% and 2.3%, respectively (P < 0.01). In
      2-7 years after intervention, there were only one or two schistosomiasis cases
      each year. At the application stage, no schistosomiasis cases were found among
      Model B target population in two successive years after intervention. CONCLUSION:
      The practice of Model B can be extended to other schools in endemic area to
      develop "schistosomiasis-free schools".

PMID- 19856501
TI  - [Real-time PCR in analyzing DNA extraction from Cryptosporidium oocysts].
AB  - OBJECTIVE: To compare the quality and quantity of DNA extracted from
      Cryptosporidium oocysts by different methods. METHODS: Cryptosporidium oocysts
      were treated with different kinds of lysis buffers from USA Promega (Promega) and
      Shanghai Generay (Generay) commercial DNA extraction kits, 2% Triton X-100 and 5%
      guanidine thiocyanate. The oocysts were then broken down by freeze-thawing,
      proteinase K and sonication. Genomic DNA was purified using the commercial kits
      or Chelex-100. Real-time PCR technique was used to determine the copies of
      Cryptosporidium oocyst wall protein (COWP) gene. The Promega commercial DNA
      extraction kit was used as control. RESULTS: The Promega kit resulted in a higher
      copy number of COWP gene [(6.45-9.86) x 10(6)] than that of Generay commercial
      DNA kit [(2.38-3.69) x 10(6)], 5% guanidine thiocyanate [(1.27-21.29) x 10(5)] or
      2% Triton X-100 [(2.06-866.70) x 10(3)] , respectively. The method of freeze
      thawing plus proteinase K plus sonication provided the highest copy number of
      COWP gene. CONCLUSION: The method of freeze-thawing + proteinase K + sonication
      is most effective. The effect of DNA extraction by Generay kit and 5% guanidine
      thiocyanate is similar to that of Promega kit.

PMID- 19856502
TI  - [Identification of calf-origin Cryptosporidium bovis Shanghai isolate by nested
      PCR].
AB  - OBJECTIVE: To identify a strain of Cryptosporidium in the feces of naturally
      infected calf in Shanghai. METHODS: Stool sample was examined by modified acid
      fast staining. The size and morphology of the oocysts were microscopically
      determined. Genomic DNA was extracted from the oocysts isolated from feces of a
      naturally Cryptosporidium-infected calf. According to the sequence of
      Cryptosporidium 18S rRNA gene, two pairs of primers were designed and
      synthesized. The PCR products was amplified by nested PCR and sequenced in double
      directions. Homology searches were done over the Web using the program Blast.
      Phylogenetic tree was constructed with NJ method by MEGA4.0 software. RESULTS:
      Oocysts of the Shanghai isolate were round or elliptical with a size of (5.6 +/-
      0.49) microm x (5.2 +/- 0.51) microm. Nested PCR resulted in fragments of
      approximately 810 bp, and the 18S rRNA nucleotide sequence had 100% identity with
      C. bovis from Brazil (GenBank Accession No: 151935628). This isolate was
      clustered in the same clade with C. bovis from Brazil. It showed an identity of
      99% with the sequences of C. bovis from Qinghai Province of China, Mongolia, USA,
      and Tunisia. CONCLUSION: The calf-origin Cryptosporidium derived from Shanghai
      has been identified as C. bovis.

PMID- 19856503
TI  - [A case of lymphocytic leukemia complicated with Strongyloides stercoralis
      infection].

PMID- 19856504
TI  - [Preliminary application of PCR-based assay for the detection of Neospora caninum
      in bovine aborted fetus].
AB  - OBJECTIVE: To establish a PCR diagnostic method based on Nc-5 gene of Neospora
      caninum, for being used to detect Neospora in brain tissues of bovine aborted
      fetus. METHODS: Specific primers were designed and synthesized based on the
      reported Nc-5 gene of N. caninum (GenBank Accession No. AY459289). Using genomic
      DNA from N.caninum as templates, Nc-5 gene was amplified by PCR. The PCR product
      was cloned into pMD18-T vector, transformed into Escherichia coli JM109 and then
      sequenced. To evaluate the specificity of the PCR, genomic DNA of Theileria
      annulata, Babesia bovis, Toxoplasma gondii, Leishmania donovani and standard
      strain of N. caninum were used as a template in the PCR. For determining the
      detection limit of amplification procedure, PCR was run on a dilution series of
      genomic DNA from N. caninum (1.562 5-200 ng/ml). Brain tissue samples of 32
      aborted fetuses were detected by PCR-based assay, and 23 blood samples from
      mothers were tested by ELISA. RESULTS: The amplified DNA fragment (350 bp) had a
      high identity of 98% with the Nc-5 gene sequence of N. caninum (GenBank Accession
      No. AY459289). The PCR was specific for N. caninum and allowed the detection of
      3.125 pg DNA of the parasite, while no amplification occurred with the other four
      species of protozoa. PCR-based assay and ELISA showed a positive rate of 18.8%
      (6/32) and 17.4% (4/23) of the samples tested, respectively. Moreover, all the 4
      antibody positive samples showed PCR positive. There is no significant difference
      between the two assays (P > 0.05). CONCLUSION: PCR diagnostic method is promising
      in detecting Neospora infection in brain tissues of aborted bovine.

PMID- 19856505
TI  - [Influence of baicalin on TNF-alpha and soluble intercellular adhesion molecule-1
      in rats infected with Pneumocystis carinii].
AB  - OBJECTIVE: To explore the effect of baicalin on tumour necrosis factor-alpha (TNF
      alpha) and soluble intercellular adhesion molecule-1 (sICAM-1) of
      immunosuppressed rats infected with Pneumocystis carinii. METHODS: Forty-nine SD
      rats were randomly divided into 7 groups: normal control (A), immunosuppressed
      control (B), SMZ/TMP control (C), baicalin prevention (D), low dose (E), moderate
      dose (F) and high dose (G). Rats of group D received six injections at three-day
      intervals with 3.5 mg dexamethasone sodium phosphate for 3 weeks, while groups B,
      C, E, F and G received same immunosuppressor but for 6 weeks. Rats in group D
      were given 100 mg/kg baicalin daily for 5 weeks, and groups C, E, F and G were
      given 250 mg/kg SMZ+50 mg/kg TMP, low dose [100mg/(kg x d)], moderate dose [200
      mg/(kg x d)], and high dose [400 mg/(kg x d)] baicalin daily for 2 weeks,
      respectively. At the end of 8th week after immunosuppression, the contents of TNF
      alpha and sICAM-1 in peripheral blood were detected by radioimmunoassay (RIA) and
      ELISA, respectively. The pathological change of lung was observed by lung imprint
      smear with gomori methenamine silver (GMS) staining and lung section with
      hematoxylin-eosin (HE) staining. RESULTS: The content of TNF-alpha in group D
      [(2.14 +/- 0.14) ng/ml], group E [(2.57 +/- 0.15) ng/ml], group F [(1.46 +/-
      0.14) ng/ml], group G [(1.12 +/- 0.13) ng/ml] and group C [(1.59 +/- 0.14) ng/ml]
      were higher than that of group A [(0.70 +/- 0.21) ng/ml] (P < 0.05, P < 0.01),
      and lower than group B [(3.65 +/- 0.73) ng/ml] (P < 0.01). The content of sICAM-1
      in group D [(618.68 +/- 52.42) pg/ml], group E [(814.29 +/- 61.11) pg/ml], group
      F [(498.08 +/- 32.56) pg/ml], group G [(377.06 +/- 56.56) pg/ml] and group C
      [(386.95 +/- 44.98) pg/ml] were lower than group B [(1 247.39 +/- 288.57) pg/ml]
      (P < 0.05). Compared with immunosuppressed control group, there were less
      alveolar interstitial lymphocytes, foamy intra-alveolar exudate and inflammation
      of lung tissue in rats of drug treatment groups. CONCLUSION: Baicalin can
      decrease the contents of TNF-alpha and sICAM-1, and alleviate inflammation in
      lung tissues of rats infected with Pneumocystis carinii.

PMID- 19856506
TI  - [Experimental establishment of life cycle of Clonorchis sinensis].
AB  - OBJECTIVE: To establish and maintain the life cycle of Clonorchis sinensis in
      laboratory. METHODS: Adult worms and eggs of Clonorchis sinensis were collected
      from naturally infected cats. Eggs were ingested by freshwater snails in
      aquarium. When the cercariae were released from infected snails, they invaded
      into freshwater fishes. From the 30th day on after the release of cercariae, the
      infection rate and metacercariae density in freshwater fishes were determined.
      RESULTS: After 95 days the infected snails began shedding cercariae in a
      temperature range of 24.3 -37.2 degrees C, and no cercariae were found under 20
      degrees C. The infection rate in the snails Parafossarulus striatulus and
      Alocinma longicornis was 12.5% and 18.0%, respectively. Metacercariae were found
      in fish at 30 days after cercariae infection, and matured metacercariae were
      detected in 45 days. The number of metacercariae per gram of fish meat in
      Pseudorasbora para, Ctenopharyngodon idellus, Rhodeus sinensis,
      Hypophthalmichthys nobilis, Cirrhinus molitorella, Carassius auratus, Cyprinus
      carpio and Oreochromis niloticus was 1 792, 16, 8, 6, 5, 4, 4, and 2,
      respectively. Rats and cats were fed with metacercariae from fish to receive
      adult worms. CONCLUSION: Life cycle of Clonorchis sinensis has been established
      and maintained in the laboratory.

PMID- 19856507
TI  - [Distribution of food-borne parasitic diseases and dietary habits in human
      population in Guangxi].
AB  - OBJECTIVE: To investigate the distribution of common food-borne parasitic
      diseases and dietary habits in Guangxi. METHODS: In the survey from 2002 to 2005,
      questionnairing, fecal examination, ELISA or skin test were applied in the
      endemic areas of clonorchiasis, taeniasis, cysticercosis, trichinelliasis or
      paragonimiasis in Guangxi Zhuang Autonomous Region. 13 990 residents at 27 sites
      in 9 counties were examined for clonorchiasis, 22772 residents at 22 sites in 10
      counties for taeniasis, 9 638 residents at 20 sites in 10 counties for
      trichinelliasis and 9 347 residents at 18 sites in 6 counties for paragonimiasis.
      RESULTS: Among 109 counties, residents in 64 counties (59.8%) were found with
      local habit of eating raw meat, covering Han and other 6 ethnic groups (Zhuang,
      Yao, Miao, Maonan, Dong and Buyi) . Various animal food such as fish, pork, pork
      liver, swine blood, beef, ox blood, chicken blood, goat blood, crab, shrimp,
      clamworm, snail, oyster, and duck meat were consumed in raw with or without
      seasonings, or by ways of hot-pot, pickle, dipping in boiling water or wine
      soaked. Food-borne diseases such as clonorchiasis, taeniasis, cysticercosis,
      trichinelliasis and paragonimiasis were prevalent in the Region. The survey
      showed that clonorchiasis is prevalent mainly in the river basins of Yongjiang,
      Zuojiang and Youjiang in the middle-west and southern part of the Region with a
      prevalence of 9.8%, taeniasis and cysticercosis in the north and middle-north
      such as Rongshui prevalence of 43.3% and 2.1% respectively, Bingyang (2.1% and
      1.0%) and Tianlin (1.6% and 1.1%) counties. Sporadical cases of trichinelliasis
      were found in the counties of Debao, Baise, Luzhai and Nandan with positive rate
      9.8%, 6.4%, 5.3% and 3.1% by serological test. Skin test on paragonimiasis among
      residents in sampled areas revealed a positive rate of 2.6% and the cases mainly
      distributed in Rongshui, Longsheng and Quanzhou counties. CONCLUSION: Consumption
      of raw or undercooked meat is popular in the local residents especially the
      ethnics, which is an important factor in the prevalence of food-borne parasitic
      diseases.

PMID- 19856508
TI  - [Effect of synchronous chemotherapy for residents and livestock against
      schistosomiasis japonica for 12 years in Jingzhou city].
AB  - OBJECTIVE: To evaluate the anti-schistosomiasis effect of World Bank loan for
      schistosomiasis control project 1992-2001 in Jingzhou City, Hubei Province, and
      observe the endemic situation after two years of the end of the project. METHODS:
      By a retrospective longitudinal survey, information from annual reports was
      collected, which included disease screening, treatment and extended chemotherapy
      for human population and livestock, the distribution of Oncomelania hupensis and
      health education information from eight counties in Jinzhou prefecture from 1992
      to 2003. Statistical u test was used for phased retrospective dynamic analysis.
      RESULTS: In the year 2001, schistosomiasis patients (77 009 cases) were 45.2%
      less than that of 1992 (140438 cases). The number of acute and advanced cases (63
      and 1 032 cases, respectively) was 74.2% and 43.9% less than those of 1992 (244
      and 1 841 cases, respectively). The average infection rate among residents was
      also reduced from 7.8% of 1992 to 4.7% (u = 28.864, P < 0.01). Number of infected
      cattle in 2001(3 454) was 57.0% less than that of 1992 (8 035), and the
      prevalence in cattle was reduced from 7.9% of 1992 to 3.7%, decreased by 53.2% (u
      = 9.338, P < 0.01). Snail-ridden area in 2001 was 19 368 hectares, 23.7% less
      than that of 1992 (25 395 ha). In 2003, two years after end of the project,
      number of acute schistosome infections was 100 cases, 59.0% less than that of
      1992, but 58.7% more than that of 2001. The average infection rate in humans
      increased to 8.4% in 2003, 7.7% and 78.7% more than that of 1992 and 2001,
      respectively (u = 6.453, 34.804, P < 0.01). The average infection rate in cattle
      increased to 6.5% in 2003, 17.7% less than that of 1992, but 75.6% more than that
      of 2001 (u = 3.061, 5.894, P < 0.01). Snail-ridden areas also increased in 2003
      with 29.3% and 69.6% more than that of 1992 and 2001, respectively. CONCLUSION:
      Synchronous chemotherapy for residents and livestock can reduce the prevalence of
      schistosomiasis and control its transmission effectively in several year period,
      but the disease may re-emerge after chemotherapy stopped.

PMID- 19856509
TI  - [Research progress on the technology of microsporidian detection].
AB  - The microsporidia are obligate intracellular eukaryotic parasites. They have been
      paid more attention as being the emerging pathogen of human, so it is important
      to control microsporidiosis using fast and precise detecting technology. In order
      to provide a reference for controlling microsporidian infection effectively, this
      paper reviews the progress of studying on the detecting technology from the
      microscopic staining methods, immunological and molecular biology.

PMID- 19856510
TI  - [GIS/RS/GPS application in the study of relationship between natural factors and
      malaria transmission].
AB  - Malaria transmission is highly related to the natural factors such as
      temperature, rainfall and topography. Recently, the GIS/RS/GPS techniques were
      developed based on computer science and spatial analysis technology, which were
      widely used in data collection and analysis, establishment of mathematics model.
      This paper reviews the applications and development of GIS/RS/GPS techniques in
      the studies of relationship between natural factors and malaria transmission.

PMID- 19856511
TI  - [Research progress on honeybee microsporidia].
AB  - This paper summarized the new hotspots in honeybee microsporidia, covering the
      progress on taxonomic status, infection mechanism, diagnosis method,
      epidemiological regularity and control.

PMID- 19856512
TI  - [Sensitivity of Plasmodium vivax to chloroquine in Laza City, Myanmar].
AB  - Fourty-eight patients infected by Plasmodium vivax were randomly divided into
      chloroquine regimen groups A and B. Each case in group A received a total dosage
      of 1 200 mg(base) over a 3-day period (600 mg on the first day then 300 mg
      daily). Cases in group B each received total dosage of 1 500 mg (base) in 3 days
      (750 mg on the first day then 375 mg daily). Body temperature and blood smears
      were examined on days 0, 1, 2, 3, 7, 14, 21 and 28, respectively. All patients
      were negative for asexual parasites within 3 days. The cure rate on day 28 was
      100%. Results showed that P. vivax is sensitive to chloroquine in Laza, Myanmar,
      and chloroquine can still be used for the imported vivax malaria cases at the
      China-Myanmar border.

PMID- 19856513
TI  - [Cloning and sequence analysis of the egG1Y162 gene of Echinococcus granulosus].
AB  - A pair of primers (egG1Y162) were designed according to the nucleotide sequence
      of Echinococcus multilocularis emY162 antigen gene. Using genomic DNA and cDNA
      from protoscoleces and adult worms of E. granulosus as templates, PCR was
      performed with the primers to obtain fragments of egG1Y162 gene. PUCm-T/egG1Y162
      recombinant plasmids and PUCm-T/egY162 cDNA recombinant plasmids were constructed
      and identified by PCR, digestion with restriction enzyme and sequencing. The
      egG1Y162 antigen gene was amplified in protoscoleces and adult worms of E.
      granulosus. The size of the egG1Y162 gene was 1 648 bp and cDNA was 459 bp, and
      GenBank accession numbers were AB458258 and AB458259, respectively.

PMID- 19856514
TI  - [Routine blood test and bone marrow examination in visceral leishmaniasis
      patients in Kashi Prefecture].
AB  - The examinations of blood and bone marrow in 125 patients with visceral
      leishmaniasis revealed that seven routine parameters of the blood samples were
      below the lower limit of normal in most cases and 64.8% of the cases showed
      complications with iron deficiency anemia (IDA) and cell maturation disorders.
      Therefore, iron deficiency anemia and significant reduction of blood components
      can be used as indicators on the severity of Leishmania infection.

PMID- 19856515
TI  - [Epidemiological investigation on an outbreak of amoebic dysentery in Jiangshan
      City of Zhejiang Province].
AB  - The investigation was carried out from 15 May to 10 June 2006 among diarrhea
      patients of two schools and periphery residents in Hecun Town, Jiangshan City.
      Stool samples were examined for Entamoeba histolytica. Water samples were taken
      for microbial analysis. 31 cases with E. histolytica were found,with 74.2% (23
      cases) of students and preschool children. 9 cases were found in Liuyi
      kindergarten and 8 cases in Hecun central primary school with a prevalence of
      7.4% and 0.65%, respectively. Among 594 asymptomatic close contactors, 9 cases
      (1.5%) were carriers of cysts. Of the 31 cases, 22 were found with no habit of
      handwashing before eating or after defecation, and 14 cases had a close contact
      to the patients. No amoebic cysts or trophozoites were found from 12 water
      samples collected from schools or patient's houses, but the Escherichia coli
      level exceeded the national standard in 7 samples.

PMID- 19856516
TI  - [Morphological comparison of two species of Theileria in sheep].
AB  - Two splenectomized sheep were infected respectively with Theileria luwenshuni and
      T. uilenbergi, 2 species identified by PCR. When piroplasms were found in blood
      smears from ears of the sheep, morphological observation on the Theileria spp.
      was carried out by optical microscopy. By Giemsa staining, the cytoplasm
      exhibited in slight blue and nucleus in purple. The two Theileria species
      displayed various shapes, but pyriform-shaped, round-shaped and needle-shaped
      parasites appeared in every stage of the infection. In fact, there is no
      significant morphological difference between the two species.

PMID- 19856517
TI  - [Field investigation of sparganosis in frogs in Huaxi area].
AB  - Frogs were caught from 4 towns in Huaxi of Guiyang and dissected. The collected
      spargana were used to infect young dogs for species identification. Results
      showed that the wild frogs were identified as Rana nigromaculata, and the
      infection rate was 16% (131/818) with an average intensity infection of 3.44 per
      frog, The tapeworm obtained from an infected dog was specified as Spirometra
      mansoni.

PMID- 19856518
TI  - [A case of severe strongyloidiasis].

PMID- 19856519
TI  - Swine flu outbreak: dissemination of information.

PMID- 19856520
TI  - [One case with 14 tapeworms (Taenia saginata asiatica) expelled].

PMID- 19856521
TI  - Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial
      induces strong and broad immune responsiveness to booster vaccination in adults.
AB  - Priming a population with a pre-pandemic vaccine is being considered to maximize
      the response upon subsequent vaccination with a true pandemic vaccine more
      closely matched to the causative pandemic strain. The present study explored this
      prime-boost concept by evaluating different primary schedules with the pre
      pandemic A/Vietnam/1194/2004(NIBRG-14) vaccine, containing 3.75 microg of HA,
      followed by a 6-month booster with a vaccine formulated with 3.75 microg HA of
      either the same strain or with A/Indonesia/05/2005(IBCDC-RG2), a heterologous
      strain from a different clade. In this multicentre, open, randomized study
      (NCT00430521) we measured immune responses in four groups (N = 48-60) of adults
      aged 18-60 years who received a single booster administration of either
      A/Indonesia/05/2005 or A/Vietnam/1194/2004 vaccine 6 months after a 1- or 2-dose
      (given 21 days apart) primary vaccination with A/Vietnam/1194/2004. All prime
      boost schedules assessed induced early (7 days post-booster) humoral responses
      that met regulatory acceptance criteria. Two doses of A/Vietnam/1194/2004 given 6
      months apart achieved equivalent homologous seroprotection after the second
      vaccination (89.6%), when compared to two doses given 21 days apart (92.7-93.2%).
      Remarkably, two doses of A/Vietnam/1194/2004 given 6 months apart induced a
      higher cross-reactive seroprotection against A/Indonesia/05/2005 (83.3%) when
      compared to two doses given 21 days apart (41.5-54.5%). A 6-month
      A/Indonesia/05/2005 booster dose after one primary dose of A/Vietnam/1194/2004
      vaccine induced 92.5% seroprotection against A/Indonesia/05/2005 and 98.1%
      against A/Vietnam/1194/2004. Since a single booster 6 months after one primary
      dose of AS03-adjuvanted vaccine induces strong and rapid seroprotective immune
      response against both homologous and heterologous H5N1 strains, these results
      might have important implications for public health strategy aiming to organize
      vaccination campaigns with pre-pandemic vaccines.

PMID- 19856523
TI  - S4: Pre-pandemic and pandemic vaccination. 16 September 10.30-12.00.

PMID- 19856522
TI  - S2: Seasonal vaccination of health care workers. 15 September 13.30-15.00.

PMID- 19856524
TI  - S6: Equitable use of intervention strategies in a pandemic. 16 September 15.30
      17.00.

PMID- 19856525
TI  - Abstracts from the 5th International Society for Computational Biology Student
      Council Symposium at the 17th Annual International Conference on Intelligent
      Systems for Molecular Biology and the 8th European Conference on Computational
      Biology. June 27, 2009. Stockholm, Sweden.

PMID- 19856526
TI  - [About machines and instruments (I): the body of the automaton in the work of
      E.T.A. Hoffmann].
AB  - Immediately after becoming interested in animal magnetism, and undoubtedly as a
      result of this interest, E.T.A. Hoffmann used automata as the central characters
      in some of his most notable works. This paper aims to show how this interest
      reveals the author's critical attitude towards a conception of the human being
      which, developing in parallel to anatomy-based medicine, had led in the
      eighteenth century to a doctrine whose most complete expression is to be found in
      "L'homme machine," by J.O. De La Mettrie. Nowadays we can see these tales, like
      those dedicated to animal magnetism, as a cry of alarm against one of the
      consequences of such a mechanical conception of a human being: the growth of
      "biopower," or of "biopolitics," terms coined by Foucault in his last works; but
      also against the risks entailed by the Promethean drive of modernity.

PMID- 19856527
TI  - [Appropriation of a healthcare space by a professional elite: physicians of the
      "Hospital Real" of Granada in the 16th century].
AB  - This study investigates the staffing by physicians of the "Hospital Real" in the
      city of Granada in the 16th century, focusing on the selection processes that
      preceded their respective and successive appointments. The aim is to illustrate
      the determination shown by this class of professionals to claim this healthcare
      space and the academic and socio-cultural requirements that they had to meet in
      return. These included the possession of a university degree and the
      accreditation of reputable surgical experience and, to a lesser degree, "limpieza
      de sangre" (proof of Spanish Christian ancestry) and the title of physician
      awarded by the local court of the Inquisition.

PMID- 19856528
TI  - Micafungin - the newest echinocandin.
AB  - Micafungin is one of three currently FDA-approved echinocandins. It has potent in
      vitro activity against Candida species including non-albicans Candida and azole
      resistant Candida species and has also demonstrated clinical efficacy against
      deep-seated Candida infections. Additional in vitro data and preliminary clinical
      efficacy studies suggest that it also has utility for the treatment of infections
      caused by Aspergillus species. However, its approved indications remain for the
      treatment of both invasive and esophageal candidiasis and for the prophylaxis of
      Candida infections in patients undergoing hematopoietic stem cell
      transplantation. is generally well tolerated with few significant adverse
      effects.

PMID- 19856529
TI  - NAPNAP position statement on the doctorate of nursing practice (DNP).

PMID- 19856530
TI  - [Military, sailors and the sick poor: contribution to the history of the San Juan
      de Dios Hospital in Cartagena de Indias (18th century)].
AB  - This article explores the history of the San Juan de Dios Hospital in Cartagena
      de Indias, at the end of the 18th century. Its activities and evolution cannot be
      understood unless they are analyzed within the context of the Bourbon sanitary
      reforms. it was precisely at that time when these reforms were being implemented
      in Nueva Granada. One of the goals of the reforms was to improve the health of
      the population in order to discipline the vassals, to promote the growth of the
      workforce and to increase the Crown's wealth. The text reviews different aspects
      of the institution, and how it operated. It examines the budget, its expenses,
      and the dynamics of the hospital population and of its employees. In doing so, it
      intends to explain what the hospital offered to the city's various social groups.

PMID- 19856531
TI  - [The origins of the Pavilion Lazaretto: quarantine architecture between the 18th
      and 19th centuries].
AB  - The model of pavilion lazaretto was built above the scientific basis established
      during the hospital reform process held in France on the lasts decades of the
      eighteenth century. The morphological solutions adopted for the new quarantine
      taxonomy has not been given by the example borrowed by the new typology of
      hospital as resulted in this discussion, but by existing quarantine and detention
      facilities in general. In this paper we will analyse all factors that have
      influenced in the configuration of this model of lazarettos.

PMID- 19856532
TI  - ["Galli vocant istvm morbvm morbvm eius cvivs est.": another designation for the
      French disease].
AB  - Berengario da Carpi, in "Anatomiam Mundini Commentarius" (1521) writes "morbus
      eius cuius est" as equivalent of "Morbus Gallicus." We aim to understand this
      expression in its morphology as well as in the way the medical profession
      considered this illness at his time.

PMID- 19856533
TI  - "Esteeme a little of fish": fish, fishponds, and farming in eighteenth-century
      New England and the Mid-Atlantic.
AB  - Prior to the advent of scientific aquaculture in the mid-nineteenth century,
      English farming manuals of the seventeenth and eighteenth centuries instructed
      American colonists in the "art of husbandry," imparting advice and passing on the
      best-known strategies for keeping and rearing fish in enclosed ponds. The
      development of such ponds in the New England and Mid-Atlantic colonies during the
      eighteenth century marked the culmination of a long process by which British
      American colonists adapted to declines in natural fish populations brought on by
      over-fishing and disruption of habitat by water-powered mills. The development of
      private fishponds as an increasingly important component of American mixed
      husbandry practices in long-settled areas by the end of the eighteenth century
      illustrates early American farmers' ability to successfully adapt to self-wrought
      changes in their physical environment.

PMID- 19856534
TI  - Diversification of de-agrarianization? Income diversification, labor, and
      processes of agrarian change in southern and northern Malawi, mid-1930s to mid
      1950s.
AB  - This article investigates the links between market-oriented activities and
      subsistence production among peasant farmers in the Thyolo and Mzimba districts
      in Malawi from the mid-1930s to the mid-1950s. The two districts were chosen
      because of their differences in terms of land-labor ratios, quality of soils, and
      structure of market engagement. Exploring the different paths of agrarian change
      in these two districts demonstrates that they were dependent on the structure of
      market engagement and its effects on the supply and flexibility of labor. African
      agricultural history is best understood when agricultural systems are viewed in
      connection to the overall economic activities of rural households. More simply
      put, the dynamics of agrarian change in rural Africa cannot be understood without
      linking such changes to the wider economy and their impact on local labor
      processes.

PMID- 19856535
TI  - "The extension service is not an integration agency": the idea of race in the
      Cooperative Extension Service.
AB  - This article is an institutional history of the development of race policy within
      the federal Cooperative Extension Service. It demonstrates that the popular
      belief in African-American inferiority and pragmatic political compromises aimed
      at creating a bureaucracy serving the nation's agricultural constituency and
      ensuring its longevity, led to a conscious marginalization of African-American
      interests within the program. Federal extension officials not only tolerated, but
      actively supported, discrimination within the southern the southern branches of
      the service. African-American leadership protested against the adverse effects of
      racial policies in the Extension Service from the very beginning. While there
      were some limited positive gains in the number of staff and availability of
      services for rural African-Americans, these changes did not challenge the
      suzerainty of whites over the program. In the post-World War II era -- especially
      after 1950 -- African-Americans confronted white extension leadership. Extension
      officials hid behind a bureaucratic facade and a flawed interpretation of the
      federal-state cooperative agreement to delay institutional restructuring.
      Political appointees pushed the service toward policies of racial justice;
      however, extension leadership continued to move slowly on fundamental
      transformation. As a result, the adjustments did not lead to a fundamental re
      thinking of race policy in the service and ultimately contributed to the
      disappearance of the African-American extension force to a significant degree.

PMID- 19856536
TI  - [Qualified information supporting continuous dermatology training. Editorial].

PMID- 19856537
TI  - Paradox of precision: bright tobacco as technology of transfer, 1880-1937.
AB  - This article compares two episodes of technology transfer in the 1890s: the
      movement of bright tobacco production technology to south-central Africa with the
      spread of the crop to eastern North Carolina and South Carolina. It finds
      similarities in the people who introduced the crop, but significant differences
      in the methods used to produce it. This is troubling because the type is defined
      by the cultivation and especially the curing techniques used to produce it; it is
      also often described in the historical literature as "Virginia tobacco," even
      when grown elsewhere. the technological differences are the product of different
      environments, which include not only the climate but also many elements of the
      technological system beyond immediate human control: the availability and
      organization of labor, differences in market structures and marketing
      institutions, and the government incentives provided to buyers. Therefore, this
      essay takes as its subject the paradox inherent in the official classification of
      tobacco types regulated by the USDA and argues that varietal types represent a
      form of market regulation disguised as botanical taxonomy.

PMID- 19856538
TI  - Measuring the natives: Beatrice Blackwood and Leonard Dudley Buxton's work in
      Oxfordshire.

PMID- 19856539
TI  - Ancient law and Indian Rights: an historical perspective from the Argentine
      Chaco.

PMID- 19856540
TI  - Bigger than a bread box.

PMID- 19856541
TI  - Identifying and overcoming barriers to learning: low literacy levels and vision
      impairment in elderly diabetics.

PMID- 19856542
TI  - The least, the lost, and the last.

PMID- 19856543
TI  - Provocation and progress.

PMID- 19856544
TI  - The importance of cytomegalovirus-specific antibodies for the prevention of fetal
      cytomegalovirus infection or disease.
AB  - Primary maternal infection with cytomegalovirus (CMV) during or just before
      pregnancy is responsible for nearly all congenital infections where the baby is
      symptomatic at birth. If primary maternal CMV infection occurs during the first
      or second trimester, between one-third and one-half of fetuses become infected,
      and between one-half and one-third of infected fetuses go on to have symptoms at
      birth. Experiments using a guinea-pig model of CMV infection in pregnant dames
      (and subsequent observational studies in humans) indicate a beneficial effect is
      associated with administering high-titre CMV hyperimmunoglobulin (HIg) to
      pregnant women with primary CMV infection. HIg appears to be effective for
      treating and preventing fetal CMV infection; its mechanism of action probably
      includes reduced placental inflammation, viral neutralization associated with
      high-avidity antibodies and, possibly, downregulation of cytokine-mediated
      cellular immune responses.

PMID- 19856545
TI  - Importance of chromosomally integrated HHV-6A and -6B in the diagnosis of active
      HHV-6 infection.
AB  - Human herpesvirus-6 (HHV-6) exists as two closely related variants: A and B.
      Whereas no disease has been firmly associated with HHV-6A, variant B causes
      febrile illness in young children and is pathogenic in immunosuppressed
      transplant recipients. Chromosomally integrated HHV-6 (with either variant A or
      B) occurs in a minority of people. This phenomenon has the potential to confound
      the diagnosis of active HHV-6 infection, since chromosomally integrated HHV-6 DNA
      sequences are inherited through the germline. Therefore, viral DNA is in every
      nucleated cell in the body and can be found in a range of body fluids including
      whole blood, serum, plasma and cerebrospinal fluid. There are characteristically
      very high viral loads in whole blood (> 6 log10 HHV-6 genomes/ml) and serum (5
      log10 HHV-6 genomes/ml); these can be used to differentiate individuals with
      viral chromosomal integration from those with active HHV-6 infection, where viral
      loads are significantly lower. Increasingly, the polymerase chain reaction (to
      detect viral nucleic acid) is used for diagnosis; therefore, it is important to
      exclude HHV-6 chromosomal integration before concluding that there is evidence of
      active HHV-6 infection.

PMID- 19856546
TI  - Case report and literature review: HHV-6-associated meningoencephalitis in an
      immunocompetent adult.
AB  - Human herpesvirus type 6 (HHV-6) has been well described as an agent of
      meningoencephalitis in post-haematopoietic stem cell transplantation patients,
      but is a rare cause of meningoencephalitis in immunocompetent adults. We report
      an immunocompetent adult with HHV-6-associated meningoencephalitis. The patient
      was an elderly diabetic man who presented with fever and confusion, with
      cerebrospinal fluid (CSF) pleocytosis. HHV-6 DNA was amplified from CSF by
      polymerase chain reaction. In our review of the medical literature we examine
      clinical presentations, laboratory findings, neuroimaging studies, treatments and
      clinical outcomes in immunocompetent patients with HHV-6 meningoencephalitis.

PMID- 19856547
TI  - Summary of the 6th International Conference on HHV-6 and -7.
AB  - This article reports on selected presentations at the 6th International
      Conference on Human Herpesvirus (HHV)-6 and -7, organized by the HHV-6
      Foundation. The 98 presentations--which explored in some detail the biology of
      HHV-6, chromosomally integrated HHV-6, diagnostic testing and manifestations of
      HHV-6 infection in disease. Associations between HHV-6 and -7 and a wide variety
      of diseases were reported, and are made plausible by the remarkably broad
      cellular tropism of the viruses in vitro. To determine whether these associations
      are causal, it is imperative to improve diagnostic technologies and to expand
      studies of possible disease associations. It also is important to expand on
      recent encouraging work identifying effective in vitro treatments for both HHV-6
      and -7.

PMID- 19856548
TI  - Antiretroviral drug resistance testing in adult HIV-1 infection: 2008
      recommendations of an International AIDS Society-USA panel.
AB  - Resistance to antiretroviral drugs remains an important limitation to successful
      human immunodeficiency virus type 1 (HIV-1) therapy. Resistance testing can
      improve treatment outcomes for infected individuals. The availability of new
      drugs from various classes, standardization of resistance assays, and the
      development of viral tropism tests necessitate new guidelines for resistance
      testing. The International AIDS Society-USA convened a panel of physicians and
      scientists with expertise in drug-resistant HIV-1, drug management, and patient
      care to review recently published data and presentations at scientific
      conferences and to provide updated recommendations. Whenever possible, resistance
      testing is recommended at the time of HIV infection diagnosis as part of the
      initial comprehensive patient assessment, as well as in all cases of virologic
      failure. Tropism testing is recommended whenever the use of chemokine receptor 5
      antagonists is contemplated. As the roll out of antiretroviral therapy continues
      in developing countries, drug resistance monitoring for both subtype B and non
      subtype B strains of HIV will become increasingly important.

PMID- 19856549
TI  - Population representative gait speed and its determinants.
AB  - PURPOSE: Although gait speed is an important measure to obtain from older adults,
      much is uncertain about the measure. Therefore, using a large population-based
      sample, I sought to: (1) gain an indication of "normal" gait speed, (2) compare
      speed measured over 8 and 20 feet, (3) determine the relationship of several
      independent variables with gait speed. METHODS: The National Health and Nutrition
      Examination Survey (NHANES) 2001-2002 provided the following data for individuals
      (> or = 50 years, n = 1923): gait speed over 8 and 20 feet, age, stature,
      adiposity, and isokinetic knee extension force. Estimates of normal gait speed
      were calculated for gender and age strata. Speeds over 8 and 20 feet were
      compared using a paired t-test and a Pearson correlation. The relationship
      between the independent variables and gait speed were examined using Pearson
      correlations and forward multiple regression analysis. RESULTS: Mean gait speeds
      were 3.26 ft/sec and 3.29 ft/sec over 8 and 20 feet, respectively. Speeds over
      the distances differed significantly (p = .002) but not meaningfully; they were
      correlated strongly (r = .933, p < .001). Age, stature, knee extension force, and
      waist circumference correlated significantly (p < .004) with gait speed over both
      distances. Age, gender, knee extension force, waist circumference, and stature
      were shown by multiple regression to predict walking speed over both 8 feet (R =
      .459, p < .001) and 20 feet (R = .506, p < .001). CONCLUSIONS: The estimates of
      normal gait speed provided are slower than many of those previously published but
      may be more representative of the population. As gait speed measured over 8 and
      20 feet are comparable, using the shorter distance appears justifiable.
      Individuals walk faster who are younger, male, taller, stronger, and have smaller
      waists.

PMID- 19856550
TI  - Minimum detectable change in gait velocity during acute rehabilitation following
      hip fracture.
AB  - PURPOSE: Early ambulation and rehabilitation are recommended for patients
      undergoing surgical fixation of hip fracture. Gait velocity may be used as an
      outcome measure for these patients during acute rehabilitation. As an outcome
      measure, an estimate of meaningful change (responsiveness) in gait velocity for
      these patients, however, has not been described. The minimum detectable change
      (MDC) is a value that represents true change in a measure beyond that accounted
      for by measurement error. The purpose of this study was to quantify MDC in gait
      velocity as an index of responsiveness for persons in the acute stage of
      rehabilitation following hip fracture. METHODS: The study design was a
      descriptive cohort study with one repeated measure. A volunteer sample of 16
      subjects over the age of 65, at a mean of 4.7 days postsurgical fixation of
      unilateral hip fracture, participated in the study. The study was conducted in an
      acute care rehabilitation practice in a large, tertiary care hospital. We
      measured gait velocity with the 10-meter walk test, estimated test-retest
      reliability with an intraclass correlation coefficient and quantified
      responsiveness of gait velocity as the MDC at a 95% level of confidence. RESULTS:
      Mean gait velocity was 15 cm/s and the test-retest reliability coefficient was
      equal to 0.823. The MDC in gait velocity during acute rehabilitation following
      surgical repair for hip fracture was 8.2 cm/s. CONCLUSIONS: Self-selected gait
      velocity in patients during acute rehabilitation following surgical fixation for
      hip fracture must improve by 8.2 cm/s or more to designate the change as being
      real change beyond the bounds of measurement error.

PMID- 19856551
TI  - Normative data and determinants for the timed "up and go" test in a population
      based sample of elderly individuals without gait disturbances.
AB  - OBJECTIVE: To define the standard performance of elderly people without gait
      disturbances in the "Timed Up and Go" test (TUG) and investigate its
      determinants. METHODS: A population-based sample of 527 community-dwelling
      subjects, 71 to 99 years of age, was studied using a clinical, neurological, and
      cognitive standardized protocol which included the TUG (time to get up, walk 3
      meters, go back and sit down again). RESULTS: Sixty one subjects were unable to
      perform the TUG and 158 were excluded because of abnormal gait. 308 subjects
      without gait disturbances performed the TUG (mean age 77.5 +/- 5.2 years); males
      171, (55%) in 10.2 +/- 3.1 seconds (range 5-25). The TUG time was higher in
      females (11.2 +/- 3.2 seconds; males: 9.3 +/- 2.8), was positively correlated
      with age (r = 0.25, p < 0.001). Mean TUG times by age group were: 71-75 years:
      9.5 +/- 2.5 sec.; 76-80 years: 9.9 +/- 3 sec.; 81-85 years: 11.2 +/- 3.6 sec; and
      86-99 years: 12 +/- 3.8 seconds). TUG times were also related to cognitive
      impairment (Global Deterioration Scale, r = 0.27, p < 0.001), weight (r = -0.18,
      p < 0.001), height (r = -0.29, p <0.001), head circumference (r = -0.24, p <
      0.001) and nutritional status (Mini Nutritional Assessment, r = -0.31, p <
      0.001). A regression model explaining 25.8% of TUG variance included age, gender,
      weight, nutritional status and cognitive impairment as independent determinants
      of TUG scores. CONCLUSIONS: The TUG performance of elderly people over 70 without
      apparent gait disturbances depends on age and other non motor variables such as
      female gender, weight, nutritional status and cognitive impairment.

PMID- 19856552
TI  - A survey of fall prevention knowledge and practice patterns in home health
      physical therapists.
AB  - BACKGROUND AND PURPOSE: Falls are a common problem for older adults, often
      resulting in injury, fear of falling, and decreased quality of life. Fall risk
      can be decreased by modifying risk factors. Because many of the modifiable risk
      factors involve physical function, physical therapists play a key role in both
      risk factor assessment and intervention. The purpose of this study was to
      determine home health physical therapists' (1) knowledge of fall risk factors and
      interventions, and (2) practice patterns regarding assessment of fall risk.
      METHODS: A survey was developed and pilot tested for content validity and ease of
      use. Physical therapists working in home health were selected as participants
      because many of their patients are older adults at risk for falling. A list of
      home health agencies was obtained through the Alabama Department of Public Health
      website and agencies were contacted to determine the number of therapists working
      in each facility. One hundred and twenty three surveys were sent to 47 agencies.
      Forty seven surveys were returned for a response rate of 40%. RESULTS: Most home
      health physical therapists assess older adults for fall risk and provide
      interventions to decrease risk. However, slightly less than half of the surveyed
      therapists did not link interventions with specific risk factors. In addition,
      less than half of the therapists routinely refer patients to other health care
      providers to address fall risk factors. In order of importance, the highest
      ranked risk factors were environmental hazards, postural hypotension, and
      polypharmacy with muscle weakness the lowest ranked risk factor. Approximately
      80% of the therapists listed balance training and strengthening exercises as
      interventions, whereas footwear and referral to other health professionals were
      listed only by 13% and 25% of the therapists, respectively. CONCLUSION: Home
      health physical therapists are knowledgeable concerning fall risk assessment and
      intervention strategies. However, these therapists are less likely to refer to
      other health care professionals to address fall risk.

PMID- 19856553
TI  - A prototype evaluation of a computer-assisted physical therapy system for
      osteoarthritis.
AB  - PURPOSE: Osteoarthritis is a common locomotor disorder affecting many older
      people and has become a growing public health problem. Adherence to exercise is a
      key to the successful recovery of patients but is often a major problem for older
      adults with osteoarthritis. The proposed pilot study is aimed to explore the
      feasibility and acceptance of an interactive computer assisted physical therapy
      prototype for aging adults with osteoarthritis. METHODOLOGY: The prototype
      comprised of a laptop, a wireless keypad, and software designed to deliver
      customized exercise plans for each participant as prescribed by their physical
      therapists. Each participant used a wireless keypad as a remote control to
      navigate through the software that provided exercise instructions in the form of
      text and videos. Fifteen participants were enrolled in the study during their
      regular visit to an outpatient physical therapy center. They were provided with a
      15-minute instruction session first, then they were asked to use the system
      unassisted. RESULTS: Ninety percent of the patients expressed no difficulty in
      using the prototype system in this study. All participants fully understood the
      instructions given by the exercise videos and expressed their intention to use
      the system unassisted at home. CONCLUSION: The presented computer-assisted
      physical therapy prototype may play an important role in the management of
      musculoskeletal conditions in patients that require home based exercise therapy.
      Further research is warranted to evaluate the impact of the proposed computerized
      therapy system on patients with various musculoskeletal conditions.

PMID- 19856554
TI  - The impact of resistance training on balance and functional ability of a patient
      with multiple system atrophy.
AB  - PURPOSE: This case study documents the impact of a resistance-training program on
      a female patient with Multiple System Atrophy (MSA). CASE DESCRIPTION: A 68-year
      old female with a 2-year history of MSA was referred to physical therapy with a
      history of falls, increasing loss of balance and rapidly progressing lower body
      Parkinson's like dysfunction. Examination included range of motion, muscle
      strength, motor control, ambulation with and without assistive device, and
      determination of postural hypotension. Functional Reach (FR), Timed Up and Go
      (TUG), timed single limb stance (SLS), and the Performance Oriented Mobility
      Assessment (POMA) assessed safety, balance, and fall risk. Hypokinesia and
      festinating gait were observed during ambulation. Transfers sit to stand were
      functional, but with compromised safety. Impairments of muscle performance were
      found at ankle, knee, and hip. The patient wanted to be able to live at home to
      care for herself and disabled spouse. Low to moderate intensity, lower extremity
      resistance training was added (twice weekly) to an existing program of balance
      and flexibility exercises. OUTCOMES: Clinically meaningful gains were achieved in
      all functional measures, and the patient performed SLS for 10 seconds when
      previously unable. More importantly, she achieved her goal of remaining at home
      with her spouse. DISCUSSION: The addition of resistance training to an existing
      program of balance and flexibility exercises did not cause any adverse effects
      and appears to have led to improvements in balance and functional ability.

PMID- 19856555
TI  - Cancer: thinking beyond the disease.

PMID- 19856556
TI  - The evolving paradigm of adult cancer survivor care.
AB  - As a result of earlier diagnosis and improved treatment, the number of cancer
      survivors is steadily increasing, with over 11 million in the US today. These
      survivors face a multitude of long-term and late effects as a result of their
      cancer and its treatment. It is increasingly recognized that this group has
      complex and ongoing needs for medical care education, surveillance, screening,
      and support. Many organizations have helped to advance survivorship care; key
      among them are the National Coalition for Cancer Survivorship, the Institute of
      Medicine, the Lance Armstrong Foundation, and the Office of Cancer Survivorship
      of the National Cancer Institute. Important reports have defined goals of care;
      identified interventions to improve outcomes among survivors; and recognized the
      need for posttreatment surveillance, healthy lifestyle behaviors, and continued
      research in all of these areas. With these advances, survivorship care is
      emerging as a distinct component of the continuum of care in oncology.

PMID- 19856557
TI  - The care of cancer survivors is gaining new, much needed attention. article
      reviewed.

PMID- 19856558
TI  - Providing palliative care for the newly diagnosed cancer patient: concepts and
      resources.
AB  - Palliative care has evolved from end-of-life care following exhaustion of
      curative therapy to care across the cancer-management continuum. Often initiated
      concurrently with curative care at the time of diagnosis, palliative care ensures
      both effective symptom management and the best possible quality of life in four
      key domains-physical, psychological, social, and spiritual. The significant
      growth and development of palliative care in the United States is evident in that
      one in four hospitals now has a palliative care program, palliative medicine is
      now recognized as an official medical subspecialty by the American Board of
      Medical Specialties, and national programs offer comprehensive continuing
      education in palliative care for nurses and physicians. The oncology nurse who
      provides palliative care does so as part of a multidisciplinary team that
      includes not only physicians but also can involve chaplains, massage therapists,
      pharmacists, nutritionists, and other specialists. This article provides
      resources and reviews and highlights pertinent palliative care issues to guide
      oncology nurses managing newly diagnosed cancer patients.

PMID- 19856559
TI  - Palliative care is an integral part of comprehensive cancer care.

PMID- 19856560
TI  - Hearing loss in pediatric cancer survivors treated with cisplatin.

PMID- 19856561
TI  - Sexuality and body image concerns after treatment for breast cancer.
AB  - A mastectomy left this patient with sexual problems and an altered sense of
      femininity. Communication models exist that can facilitate nurse-patient
      conversations about sexuality.

PMID- 19856562
TI  - Information for patients. Peripheral neuropathy and cancer.

PMID- 19856563
TI  - Drug essentials mTOR inhibitors.

PMID- 19856564
TI  - Menopausal symptoms following tamoxifen treatment for breast cancer.
AB  - Hot flashes negatively impacted the patient's mood, stress level, sleep, and
      relationship with her husband. Breathing exercises and pharmacological management
      with a low-dose antidepressant alleviated the problem.

PMID- 19856565
TI  - Cancer care for now...and later.

PMID- 19856567
TI  - Cancer occurs in approximately 1 per 1,000 pregnancies.

PMID- 19856566
TI  - Care of the pregnant patient with cancer.
AB  - An estimated 1 in 1,000 pregnancies is complicated by cancer, and the incidence
      of cancer during pregnancy is expected to increase as women delay childbirth
      until their later years. A diagnosis of cancer and the cancer treatment process
      can be particularly difficult for the pregnant patient, and are challenging for
      the physician and nurse. This article provides an overview of cancer treatment
      during pregnancy, discusses current practice guidelines and the oncology nursing
      role in caring for this unique patient population, and highlights resources for
      clinicians and patients.

PMID- 19856568
TI  - Management of a patient with inflammatory breast cancer.
AB  - IBC is an aggressive breast cancer, sometimes mistaken for contact dermatitis, in
      which many patients do not have a palpable mass. Management of this deadly
      disease is evolving.

PMID- 19856569
TI  - Physical late effects in adult cancer survivors.
AB  - There are nearly 12 million cancer survivors living in the US today, and these
      individuals are at risk for long-term physical complications of treatment.
      Although development of less toxic treatments such as targeted therapies is
      helping to decrease the risk of physical effects in individual survivors, the
      absolute burden of physical complications in cancer survivors is increasing owing
      to growing numbers of cancer survivors combined with demographic and health
      trends such as population aging. In cancer survivors, direct effects of cancer
      and treatment exposures converge with pre-existing risk factors such as age,
      comorbidities, heredity, and lifestyle factors to elevate the risk of physical
      complications. Oncology nurses have a pivotal role to play in cancer
      survivorship. This article will provide an overview of physical effects of cancer
      and its treatment in cancer survivors, identify resources to help guide
      management, and highlight strategies for integrating cancer survivorship care and
      education into clinical practice.

PMID- 19856570
TI  - Information for patients. Diarrhea in cancer patients.

PMID- 19856571
TI  - Overview of physical long-term/late effects.

PMID- 19856572
TI  - Metabolic abnormalities in an adult survivor of pediatric craniopharyngioma.

PMID- 19856573
TI  - Levoleucovorin.

PMID- 19856574
TI  - A challenge of survivorship--healing the mind and spirit.

PMID- 19856575
TI  - Addressing psychological challenges after cancer: a guide for clinical practice.
AB  - While the completion of therapy is an important milestone in the successful
      treatment of cancer, many survivors find themselves facing a variety of
      psychological challenges after their treatment ends. This article highlights some
      of the most common psychological challenges after cancer therapy such as
      depression, anxiety, fatigue, and sexual dysfunction. Common risk factors for
      these challenges will be reviewed and methods for assessing survivors'
      psychosocial functioning in the context of a medical visit will be discussed.
      This article also will provide guidance on how to access resources and
      educational information, and how to make an appropriate referral for follow-up
      when these psychological challenges are identified.

PMID- 19856576
TI  - The psychological challenges of cancer.

PMID- 19856577
TI  - Post-trauma symptoms in cancer survivors.

PMID- 19856578
TI  - Graft-versus-host disease: a complex long-term side effect of hematopoietic stem
      cell transplant.
AB  - Hematopoietic stem cell transplantation (HSCT)/bone marrow transplantation (BMT)
      has become a central treatment modality in the management of various hematologic
      malignancies, but it is not without treatment sequelae. The major complication of
      HSCT/BMT is acute or chronic graft-versus-host disease (GVHD). GVHD is an
      immunologically mediated disease that contributes substantially to transplant
      related morbidity and mortality. The overall incidence of GVHD remains between
      30% and 60% and carries approximately a 50% mortality rate. Acute and chronic
      GVHD are complex clinical phenomena. This paper focuses on our current clinical
      understanding of GVHD as a multiphase process intricately linked to the immune
      response between the donor (graft) and recipient (host). Based on this complex
      pathophysiology, clinical nursing care is targeted at the various body systems
      affected by either acute or chronic GVHD. The article concludes with advances and
      clinical trials underway that have the potential to reduce the symptomatology of
      GVHD.

PMID- 19856579
TI  - Information for patients. Fatigue in people with cancer.

PMID- 19856580
TI  - Prophylaxis and management of graft-versus-host disease.

PMID- 19856581
TI  - Drug essentials. Small molecule multitargeted TKI therapy.

PMID- 19856582
TI  - New beginnings.

PMID- 19856584
TI  - Helping patients to navigate dietary choices.

PMID- 19856583
TI  - Nutrition during and after cancer therapy.
AB  - Diet and nutritional factors play a large role in influencing both the quality
      and quantity of life after the diagnosis of cancer. The oncology nurse is well
      positioned to: 1) help ensure that nutritional needs are met for patients who are
      newly diagnosed, undergoing active treatment, or have advanced disease; 2)
      facilitate referral of patients with more intensive nutritional needs to
      registered dietitians; and 3) promote the importance of weight management and a
      healthful plant-based diet, low in saturated fat and simple sugars, and high in
      fruits and vegetables and unrefined whole grains, to patients likely to join the
      ranks of an ever-expanding population of cancer survivors--who now constitute
      roughly 4% of the US population and number more than 11 million.

PMID- 19856585
TI  - Addressing bone loss in the cancer survivor.

PMID- 19856586
TI  - Drug essentials. The cytochrome P450 microenzyme system and targeted therapies:
      Minimizing drug interactions.

PMID- 19856587
TI  - Lower extremity lymphedema in a patient with melanoma.

PMID- 19856588
TI  - Social well-being and cancer survivorship.
AB  - There are more than 11 million cancer survivors in the US today. While awareness
      is growing of physical and psychological effects of cancer and its treatment, the
      social impact of cancer is underappreciated. This article discusses the
      significant changes in interpersonal relationships that cancer survivors can
      experience, as well as financial, employment, insurance, and legal issues. Case
      examples are provided to put these challenges in the context of survivors' life
      stage and resources. Possible interventions to address the social well being of
      cancer survivors are suggested, and the implications for developing programs that
      help survivors to face psychosocial challenges are explored.

PMID- 19856589
TI  - Information for patients. Managing cancer pain.

PMID- 19856590
TI  - Social challenges can be significant.

PMID- 19856591
TI  - Living well: a goal for all patients.

PMID- 19856593
TI  - Improving the end-of-life experience.

PMID- 19856592
TI  - When hospice is the best option: an opportunity to redefine goals.
AB  - More than 50% of patients diagnosed with cancer in 2008 died in the same year,
      according to estimates from the American Cancer Society. Clearly, while survival
      rates for many cancers continue to improve, a significant number of patients with
      cancer will not survive their disease. Hospice care provides terminally ill
      patients with a unique set of benefits, services, and support. Its goal is
      neither to prolong life nor hasten death, but rather to provide total care that
      maximizes quality of life. Less than one-third of patients receive hospice care
      near the end of life, however, and many referred patients die within days. Many
      barriers and misconceptions related to hospice care can prevent timely referrals
      and impede discussions. Also, conversations about goals of care, treatment
      preferences, and advanced care planning can be challenging and overwhelming. This
      article reviews the hospice care model and highlights ways in which oncology
      nurses can make a difference in how patients live their final days.

PMID- 19856594
TI  - Cardiotoxicities of breast cancer treatment.

PMID- 19856595
TI  - The patient with cancer-related dyspnea.
AB  - Dyspnea can be challenging to manage because it often is exacerbated by anxiety.
      Patient positioning and relaxation and breathing techniques can help.

PMID- 19856597
TI  - Hypertension management in the era of targeted therapies for cancer.

PMID- 19856596
TI  - Vesicant extravasation from an implanted venous access port.
AB  - Vesicant extravasation can occur even in patients whose nurses have years of
      experience. Nurse-physician collaboration is key to appropriate management.

PMID- 19856598
TI  - Survivorship care: essential components and models of delivery.
AB  - Cancer survivorship is now recognized as a distinct phase of cancer care, but the
      process of delivering survivorship care continues to emerge. Nurses often play a
      pivotal role during the survivorship phase by identifying patient needs and
      making appropriate referrals to address the range of issues that may arise. Some
      nurses may also be directly involved in providing survivorship-focused clinical
      care. Formal cancer survivorship programs have been established in some academic
      medical centers to address the needs of cancer survivors. Other common approaches
      to delivering survivorship care include oncology practice-based and community
      based models. Yet, many survivors receive little or no follow-up care focused on
      their cancer survivorship needs. This article will review the rationale for
      providing specialized follow-up care for cancer survivors, describe the essential
      components of that care, and assess the various models that can be employed to
      implement cancer survivorship care delivery.

PMID- 19856599
TI  - Understanding and managing nausea and vomiting.

PMID- 19856600
TI  - Drug essentials. An alkylating agent for CLL and NHL.

PMID- 19856601
TI  - Information for patients. HER2+ early breast cancer: understanding adjuvant
      treatment.

PMID- 19856602
TI  - Our fall focus on women.

PMID- 19856603
TI  - Treatment of ovarian cancer with intraperitoneal chemotherapy.
AB  - In early 2006, the National Cancer Institute (NCI) issued a Clinical Announcement
      suggesting that intraperitoneal (IP) chemotherapy should become the standard of
      care for patients with newly diagnosed stage III optimally debulked epithelial
      ovarian cancer. IP chemotherapy, the administration of chemotherapy or biologic
      therapy via catheter into the peritoneal space, is new to many healthcare
      providers (physicians, nurses, and pharmacists). The goals of this article are to
      address the rationale for IP chemotherapy, present the data supporting its use,
      and describe the nursing management of patients undergoing this treatment.
      Education of patients and staff regarding IP therapy is essential for successful
      patient outcomes.

PMID- 19856604
TI  - Challenges of IP chemotherapy for ovarian cancer.

PMID- 19856605
TI  - Understanding the needs of young adult cancer survivors: a clinical perspective.
AB  - Young cancer survivors are often unprepared to face the complexities of adjusting
      to post-treatment life. They may be pleased that treatment is ending but worried
      about losing the support, security, and scrutiny provided by their healthcare
      team. Uncertainty about the prognosis for long-term, cancer-free survival often
      threatens their sense of control, emotional well-being, functional adjustment,
      and comfort with future planning. Many feel isolated, mistrust their bodies, and
      must adjust to an altered self-image as well as changes in relationships and
      sexual functioning. It can be daunting to deal with physical late effects,
      challenges to daily living, and employment and insurance issues. Using direct
      quotations from young cancer survivors, this article shares their special
      perspective and provides guidance as to their informational, practical, and
      psychosocial needs.

PMID- 19856606
TI  - Young adult survivors face unique challenges.

PMID- 19856607
TI  - Preserving fertility in young women diagnosed with breast cancer.

PMID- 19856608
TI  - Hypothyroidism: a growing complication of cancer treatment.
AB  - Hypothyroidism is an often underreported complication of cancer treatment. With
      the growing number of biological and targeted therapies, hypothyroidism may
      become a more prevalent clinical problem. Signs and symptoms of hypothyroidism
      may be easily attributed to the cancer or cancer treatment, leading to
      unnecessary dose modifications or discontinuation of effective therapies.
      Furthermore, these symptoms have a negative effect on quality of life.
      Measurement of TSH levels in at-risk patients prior to initiating treatment and
      at regular intervals during treatment will allow early intervention and effective
      treatment of hypothyroidism.

PMID- 19856609
TI  - The emerging discipline of integrative oncology.

PMID- 19856610
TI  - Information for patients. I have HER2 positive metastatic breast cancer: is my
      treatment working?

PMID- 19856611
TI  - Vitamin D.

PMID- 19856612
TI  - Bevacizumab for renal cell carcinoma, glioblastoma, and other solid tumors.

PMID- 19856613
TI  - A descriptive study of losses associated with permanent long-term care placement.
AB  - OBJECTIVES: This qualitative study describes the process of and factors
      associated with losses connected to permanent long-term care (LTC) placement of
      the elderly. METHODS: Five subjects were recruited on a voluntary basis upon
      consultation with a staff member of a small rural long-term care facility in
      Northeast Arkansas. Researchers conducted 1 to 2, hour to hour-and-a-half
      interview sessions with each participant. In order for subjects to be included in
      the study, participants met the following criteria: placement within the past 12
      months, absence of acute disease, and cognitive ability to respond to and
      communicate during interview sessions. The interviews were taped with the
      patients' consent, and then transcribed word for word. The transcriptions were
      analyzed for emergent themes using the grounded theory approach. RESULTS:
      Qualitative analysis revealed several themes related to losses associated with
      LTC placement. These include: cohort losses, defined as losses that participants
      identified with as a cohort through lived experiences; antecedent losses, defined
      as losses that have contributed greatly to long-term care placement; and
      consequent losses, defined as losses that have been experienced as a consequence
      of placement. CONCLUSION: The cumulative nature of losses that eventually results
      in LTC placement is an important consideration in geriatric physical therapy
      practice. The study highlights the physical therapist's role in prolonging
      function, preserving quality of life, and preventing for as long as possible LTC
      placement. Losses identified as leading to LTC were found to be in alignment with
      current research. Transitioning to LTC may interfere with the need to attend to
      end-of-life role expectations, resulting in the experience of additional loss.
      Gender-related differences appear to be significant as well, with males
      expressing a marked sense of loss of meaningful activity.

PMID- 19856614
TI  - Factors influencing balance in healthy community-dwelling women age 60 and older.
AB  - PURPOSE: This study investigates the influence of the forward head posture,
      balance confidence, and physical activity levels on balance stability in healthy
      community living older women. METHODS: This descriptive study included 203 women
      volunteers [age range: 60 to 95 years, mean age of 77.33 years (SD 7.59)].
      Forward head position (FHP) was assessed via photographic analysis of a sagittal
      photo taken during the seventh task of the Berg Balance Scale (BBS). Each subject
      completed the Activity-specific Balance Confidence Scale (ABC) and the Physical
      Activity Scale for the Elderly (PASE). Balance stability was assessed using the
      Berg Balance Scale (BBS). Data analysis included descriptive indices, bivariate
      correlations, and regression analyses to determine the best predictor of balance
      stability. RESULTS: Known risk factors for balance deficits (balance confidence
      and physical activity) were significantly positively correlated, and age was
      inversely related to these factors. Forward head posture was significantly
      negatively related to the known risk factors but positively correlated to age.
      Regression analyses identified balance confidence, physical activity, and age as
      significant predictors of balance stability accounting for 43% (p < .0001) of the
      total variance in balance stability. The forward head posture variable added a
      significant 6.1% (p < .0001) to the total variance in balance stability,
      suggesting that the forward head posture plays role in balance stability.
      CONCLUSIONS: The forward head posture-balance stability relationship found in
      this population of healthy community-dwelling older women, provides evidence to
      support inclusion of postural exercises for head position in balance training
      programs. Additionally, this research further supported the relationships between
      balance stability and balance confidence and physical activity. Further research
      is needed in the domain of intervention studies which incorporate these
      variables.

PMID- 19856615
TI  - Knee extension strength and adiposity explain some of older adults' self-reported
      difficulty with mobility.
AB  - BACKGROUND AND PURPOSE: As adults lose strength with age and an increasing
      proportion of older adults are overweight or obese, this study was undertaken to
      examine the contribution of strength and adiposity to mobility difficulties among
      community-dwelling men and women at least 65 years of age. METHODS: The National
      Health and Nutrition Examination Survey (NHANES) 2001-2002 provided complete
      demographic, anthropometric, strength, and self-reported mobility data for 687
      men and women. RESULTS: Spearman correlations of adiposity (.024-.149) and knee
      extension strength (-.120-.234) with mobility difficulty were mostly significant
      but not strong. Multiple regression showed that together, body mass index, knee
      extension force, and age offered the best explanation of mobility difficulty.
      CONCLUSIONS: Adiposity and strength have relevance to the self-reported mobility
      difficulty of older adults. However, they leave most of such difficulty
      unexplained.

PMID- 19856616
TI  - Feasibility of Internet-delivered weight loss interventions among rural women
      ages 50-69.
AB  - PURPOSE: The increased availability and use of the Internet by midlife and older
      women who seek health information may provide an innovative method for delivering
      weight loss interventions. This preliminary study examined the feasibility and
      efficacy of web-based interventions for promoting weight loss among rural
      overweight and obese women ages 50-69 (M = 55.5 +/- 4.9) over a 3-month period.
      METHODS: Twenty-one Caucasian women with body mass index of 28-34.5 (M = 30.69 +/
      2.58) were randomly assigned to either a Web site only or Web site augmented
      with a peer-led support group. The Web site included recommended approaches to
      healthy eating and activity, weekly newsletters, and other resources. Body
      weight, eating, and activity measures were assessed at baseline and
      postintervention. Data analysis included 2-way repeated measures ANOVAs with
      effect sizes reported as appropriate for a pilot study. RESULTS: Sixteen women
      (76.2%) completed the study; 14 lost from 2% to 10% of their body weight, and 2
      gained 2% of their weight. Large effect sizes were found over time for body
      weight, estimated VO2max, and percentage of calories from fat. For time by group
      interaction, large effect sizes favoring the Web site plus peer-led support group
      were found for body weight, waist circumference, percent body fat, whole grain
      servings, and both systolic and diastolic blood pressure. Process evaluations
      indicated that 85.7% of women accessed the Web site weekly. There were a total of
      305 hits in the Web site only group versus 658 hits in the peer-led support
      groups. CONCLUSIONS: Internet delivered interventions appeared feasible for these
      rural women with weight loss and improvement in selected eating and activity
      measures after 3 months.

PMID- 19856617
TI  - Modification of constraint induced movement therapy in the home health setting
      for a subject with chronic hemiparesis after stroke.
AB  - PURPOSE: Constraint induced movement therapy (CIMT) has been found to be
      beneficial in upper extremity recovery of patients following a stroke. However,
      its feasibility in the home health setting has not been assessed. This
      prospective case study describes changes in upper extremity function with a
      modification of CIMT administered in the home health setting. CASE DESCRIPTION:
      The participant was an 83-year-old man 6 months post-stroke with left sided
      hemiparesis resulting from a right ischemic stroke. The residual left-sided
      weakness was complicated by pre-existing left shoulder pain due to
      osteoarthritis. He had not been able to return to many of his household chores
      and hobbies following the stroke. The intervention consisted of 1 hour functional
      task practice sessions in the participant's home 3 days each week for 5 weeks. A
      restraint of the less-affected arm was used for 5 hours each day during the
      intervention period. Activities that required use of the left upper extremity
      alone and activities that required the use of both upper extremities were
      included. Primary outcome measures used before and after the intervention
      included the Motor Activity Log (MAL) and the Wolf Motor Function Test (WMFT).
      OUTCOME: Improvements were noted in both the MAL and WMFT following the
      intervention. The participant increased his ability to perform functional
      activities and household chores. DISCUSSION: The supervised practice of
      functional tasks in the participant's home provides a clinically-relevant option
      for home-based physical therapy of the geriatric patient with stroke. This case
      study showed that the modified CIMT was feasible in the home setting for our
      participant. Further research on CIMT interventions in the home setting should
      include repeated baseline measurements and a larger number of subjects.

PMID- 19856618
TI  - Employee theft. Learn what steps you should take to avoid getting burned.

PMID- 19856619
TI  - Is your team dysfunctional?

PMID- 19856620
TI  - Play well with others.

PMID- 19856622
TI  - Back to school tip: snack right for healthy smile.

PMID- 19856621
TI  - Got calcium?

PMID- 19856623
TI  - We should remember them all... always.

PMID- 19856624
TI  - Mid-level providers offer a hollow promise to the underserved.

PMID- 19856625
TI  - I'm from the government and I'm here to help you.

PMID- 19856626
TI  - Trust and potential.

PMID- 19856627
TI  - How to handle sudden wealth.

PMID- 19856628
TI  - Understanding and managing overhead.

PMID- 19856629
TI  - Development of a clinical measure of dual-task performance in walking:
      reliability and preliminary validity of the Walking and Remembering Test.
AB  - OBJECTIVES: (1) To examine the reliability of a new clinical measure of
      simultaneous walking with performance of a working memory task, the Walking and
      Remembering Test (WART). (2) To compare older adult to younger adult WART
      performance to illustrate preliminary validity. SUBJECTS: Convenience sample of
      25 young adults (ages 22-35) and 25 older adults (ages 65-86) performed the WART
      twice. METHODS: Subjects walked 6.1 meters at their fastest safe speed along a
      path requiring a narrowed base of support in both single and dual-task (with
      simultaneous digit span task) conditions. Reductions in walking and cognitive
      performance were examined in the dual-task condition for older adults as compared
      to younger adults. MAIN OUTCOME MEASURES: Walking time, step accuracy, digit span
      memory accuracy, and dual-task costs for walking and cognitive tasks. RESULTS:
      Inter-rater reliability ICC (2,1) values were > or = .97 for walking time and
      digit span accuracy. Rater agreement of steps off the path was excellent (93%)
      for young adults and good (76%) for older adults. Test-retest reliability ICC
      (2,1) values for walking time were > or = .79. Older adults were slower and
      remembered shorter digit spans, and demonstrated greater dual-task costs for
      digit span accuracy and steps off the path than younger adults, but relative dual
      task costs for walking time were not significantly different between groups.
      CONCLUSIONS: The WART is a reliable clinical measure of dual-task memory and
      walking that can be administered safely with community-dwelling older adults.
      Expected greater dual-task costs for older adults were observed, but not as
      strongly as anticipated in this group of very active subjects. The WART provides
      information that may be useful in targeting patients for intervention to reduce
      risk of falls in dual-task conditions, but needs validation with older adults
      across a greater range of walking ability.

PMID- 19856630
TI  - Variability of the forward head posture in healthy community-dwelling older
      women.
AB  - PURPOSE: The purpose of this research was to describe the variability of forward
      head posture in healthy older women, and to investigate the influence of age on
      variability. METHODS: This cross-sectional descriptive study included 187 healthy
      community-dwelling women volunteers ranging in age from 65-96 years. The forward
      head posture (FHP) measurement was derived from a sagittal photograph. The
      subjects were asked to perform a series of standing activities, and the
      photograph was taken while the subjects were performing these activities. Data
      analysis included descriptive analysis, FHP measurement analysis for normalcy,
      one-factor ANOVA with FHP by age group, post-hoc Tukey analysis, and trend
      analysis for the age-FHP relationship. RESULTS: Three age-group normative FHP
      means were identified: 48.84 degrees (SE 0.97) for the 65-74 year old group,
      41.20 degrees (SE 0.78) for the 75-84 year old group, and 35.60 degrees (SE 1.76)
      for the 85+ year group. Significant differences were found in the FHP between
      these age groups. A subsequent trend analysis demonstrated a linear relationship
      between age and the FHP, with older women demonstrating a more severe FHP.
      CONCLUSIONS: Age-associated variability in the FHP of healthy elderly women has
      been identified. The FHP values determined by this research may serve as
      normative guidelines for clinicians when conducting postural assessments, and in
      clinical decision-making regarding possible interventions.

PMID- 19856631
TI  - Pilot case control study of postural sway and balance performance in aging adults
      with degenerative lumbar spinal stenosis.
AB  - PURPOSE: Lumbar spinal stenosis (LSS), a degenerative disease encountered in
      adults > 65 years, is a leading cause of back and lower extremity pain, weakness,
      impaired sensation and balance. The purpose of this pilot study was to determine
      whether patients with LSS demonstrate increased postural sway and impaired
      balance, compared to healthy counterparts. METHODS: Patients with varying
      severity of LSS and age and gender matched controls were recruited from a
      tertiary care hospital, yielding 6 case-control pairs. Subjects completed generic
      health status (SF-36), disease specific scales (LSS) and demographic forms.
      Medical comorbidities were extracted from medical records. Patients received a
      musculoskeletal examination and performed the Functional Reach (FR) and Timed "Up
      & Go" (TUG) tests. Stabilogram diffusion analysis (SDA) measured center of
      pressure (COP). RESULTS: Patients reported moderately impaired physical function,
      lumbar flexibility and walked with a slightly wider base of support. TUG scores
      did not differ across groups. Significantly limited FR scores indicated that
      patients had impaired dynamic balance and were at a greater risk of falls. SDA
      demonstrated no significant difference in sway for patients and controls;
      however, patients demonstrated significantly higher critical values for antero
      posterior (AP) displacement than controls. CONCLUSION: Patients with LSS, even
      those with mild symptoms, demonstrate decreased function and balance,
      particularly in the AP direction. Physical examination measures and TUG are not
      adequate to assess balance impairments or risk of falls in these patients.
      Measures such as the FR and SDA may be useful in detecting the aspects of balance
      impairments perceived by patients.

PMID- 19856632
TI  - Measurement of gait speed of older adults is feasible and informative in a home
      care setting.
AB  - PURPOSE: Although gait speed is widely recommended as a measure of activity
      limitation, it is not routinely used clinically with older adults. This
      retrospective study was undertaken to determine whether the measurement of gait
      speed is feasible and informative in a home care setting. METHODS: The therapy
      records of 27 ambulatory patients were examined for gait speed measures and other
      relevant data. RESULTS: Gait speed was documented for all patients. It was
      significantly lower than that of age and sex matched normals. A wide range of
      speeds were noted for patients who required total assistance or were completely
      independent according to Functional Independence Measure criteria or who were
      able to walk at least 150 feet. CONCLUSIONS: Measurement of the gait speed of
      older adults is feasible in a home care setting. Its sensitivity to limitations
      not revealed by other measures provides support for broader use.

PMID- 19856633
TI  - The impact of cognitive impairment on rehabilitation outcomes in elderly patients
      admitted with a femoral neck fracture: a systematic review.
AB  - OBJECTIVE: To evaluate the evidence of rehabilitation outcomes after the surgical
      repair of a hip fracture in older people with cognitive impairment. DESIGN:
      Systematic review. METHODS: Searches were conducted in MEDLINE, EMBASE, CINAHL,
      PsycINFO, Cochrane Library (Cochrane Database of Systematic Reviews, Database of
      Abstracts of Reviews of Effectiveness, and Cochrane Controlled Trials Register),
      ProQuest Dissertations, and Theses Database and bibliographies of extracted
      publications in the English language between 1990 and June 2007. Search terms
      included: dementia/Alzheimer disease/cognitive impairment, hip fracture,
      rehabilitation, outcome assessment/treatment outcome. Two independent reviewers
      undertook screening and methodological quality assessment, using the Downs and
      Black rating scale, of the extracted articles. Only studies evaluating
      rehabilitation outcomes with data analysis specific for cognitive status were
      evaluated. Sackett's levels of evidence were used to summarize the main findings.
      FINDINGS: Eleven studies met the inclusion criteria. Methodological quality of
      the studies ranged from fair to poor. The generalizability of study findings was
      limited by multiple rehabilitation settings in the acute and subacute phase
      postsurgery, multiple methods with varying thresholds for determining cognitive
      impairment and multiple functional outcome scales. CONCLUSION: There is some
      evidence that older adults with cognitive impairment who receive intensive
      inpatient rehabilitation after surgical repair of a hip fracture may be able to
      gain comparable benefit in physical function as cognitively intact patients.
      There is not enough information to guide recommendations of specific physical
      therapy interventions to optimize outcomes in this patient population. Further
      work is needed.

PMID- 19856634
TI  - Recommendations for the treatment of knee osteoarthritis, using various therapy
      techniques, based on categorizations of a literature review.
AB  - PURPOSE: This literature review is to evaluate current research articles
      pertinent to physical therapy treatment of osteoarthritis (OA) of the knee.
      Osteoarthritis of the knee is an increasingly common diagnosis, with a prognosis
      that can lead to loss in an individual's functional abilities. Literature on the
      subject of OA and its physical therapy treatment is vast and current, however,
      obtaining and analyzing it can be time consuming and costly to a Physical
      Therapist. The primary aim of this paper is to review current trends for
      treatment of OA of the knee, and to compare each intervention for effectiveness.
      This article provides a systematic categorization as well as recommendations for
      physical therapists based on current (1996 or sooner) literature. METHODS: Twenty
      two articles were located using various online databases, critically analyzed,
      and categorized using Sackett's levels of evidence. Recommendations for the
      treatment of OA of the knee by a physical therapist were then made. RESULTS: Two
      grade A recommendations, 5 grade B recommendation, and 2 grade C recommendations
      were made from the categorization of the articles. This article also contains
      recommendations outside the scope of a therapist's practice, which a physical
      therapist could consider when treating a patient with knee osteoarthritis.
      Further research recommendations are also provided.

PMID- 19856635
TI  - Case report: an evidence-based approach to examination and intervention following
      hip fracture.
AB  - BACKGROUND AND PURPOSE: A majority of older adults with hip fracture retain
      longstanding disabilities following surgery. Research suggests that more
      aggressive treatment techniques can improve outcome. The purpose of this case
      report is to describe an evidence-based approach to guide physical therapy
      examination and intervention for a woman with significant frailty recovering from
      hip fracture. CASE DESCRIPTION: The patient is a 97-year-old woman residing in a
      skilled nursing facility 3 months status-postsurgical repair of an
      intertrochanteric hip fracture. She had received 2 1/2 months of physical therapy
      care using conventional interventions, however, had not regained her prefracture
      mobility status. She agreed to participate in a progressive high-intensity
      resistance training program over a 2-month period to augment her lower-extremity
      strength and function. The 5-day training regimen emphasized resistance training
      with a weighted belt twice-weekly with endurance and balance training interposed
      on nonstrength training days. The patient's goal was to return to community
      dwelling. EXAMINATION: Lower-extremity isometric force was measured using
      handheld dynamometry. Functional mobility was assessed via Timed Up and Go, Six
      Minute Walk, Berg Balance, and gait speed tests. A 9-item Physical Performance
      Test gauged degree of frailty. RESULTS: Hip extension, hip abduction, and knee
      extension isometric force scores on the involved lower-extremity increased by 8
      kg, 3 kg, and 7 kg, respectively. Balance, frailty, and gait speed indices
      improved from 14 to 45, 8 to 18, and 0.50 to 0.83 m/s, respectively. CONCLUSION:
      Prescribed high-intensity resistance training was used to improve the patient's
      functional status 2 months after completing a conventional physical therapy
      program.

PMID- 19856636
TI  - Getting the balance right.

PMID- 19856637
TI  - Workforce planning tops agenda to prevent shortfall of nurses.

PMID- 19856638
TI  - Trained to provide better patient care through strong and focused leadership.

PMID- 19856639
TI  - Making a world of difference.
AB  - The international unit at Great Ormond Street Hospital in London treats children
      from many countries. The majority are funded by their home governments.

PMID- 19856640
TI  - Smoke-free benefits.
AB  - A systematic approach to helping patients quit smoking is being rolled out across
      primary health care, following a trial in Yorkshire and Humberside.

PMID- 19856641
TI  - The perfect balance.

PMID- 19856642
TI  - Medicines management.

PMID- 19856643
TI  - Implementing a patient assessment framework in acute care.
AB  - This article describes the secondment of a critical care practitioner to an acute
      medicine unit. The aim was to develop the acute assessment skills of the unit's
      nurses and to implement a new assessment framework. The secondment took place
      over four months from December 2007 to March 2008 at the Heart of England NHS
      Foundation Trust, Birmingham. There were several stages to the project,
      commencing with exploration of existing practice and culminating with evaluation
      of the project's effect on practice. A review of the multi-professional patient
      records was conducted six months after the conclusion of the secondment. This
      revealed that the assessment framework continued to be used in practice. The
      secondment demonstrated that supporting nurses to embrace new skills resulted in
      a change in practice. However, a permanent change cannot be assured unless
      practice is revisited and supported on a continual basis.

PMID- 19856644
TI  - Proctoclysis: emergency rectal fluid infusion.
AB  - This article describes the use and effectiveness of proctoclysis (rectal fluid
      infusion) in providing fluid resuscitation in the absence of intravenous access
      in rural and remote environments.

PMID- 19856645
TI  - Hereditary haemochromatosis: patient support and education.
AB  - Hereditary haemochromatosis is a genetic disorder resulting in iron accumulation.
      Nurses have a key role in increasing public awareness and educating patients and
      their families about the condition to enable early detection and effective
      management. This article provides a brief overview of haemochromatosis to promote
      informed nursing practice.

PMID- 19856646
TI  - Drug-induced hyperprolactinaemia.

PMID- 19856647
TI  - How can I help?

PMID- 19856648
TI  - The healing relationship.

PMID- 19856649
TI  - Cell death pathways in response to antitumor therapy.
AB  - Failure to eliminate cancer cells that have been exposed to cytotoxic agents may
      contribute to the development of resistance to antitumor drugs. A widespread
      model in present day oncology is that antitumor therapy involves the triggering
      of tumor cells to undergo apoptosis, and cells that can avoid apoptosis will be
      resistant to such therapy. Apoptosis is a defined program of cell death that is
      markedly influenced by the fact that many routes leading to it are mutated or
      deregulated in human cancer. Mutations in the tumor suppressor protein p53, a
      common feature of many cancers, may decrease the sensitivity of cells to some
      antitumor agents. Moreover, it has been increasingly reported that antitumor
      therapy not only causes apoptosis, but other forms of cell death as well, such as
      mitotic catastrophe, necrosis and autophagy, or a permanent cell arrest with
      phenotype characteristics of senescence. Mitotic catastrophe is a form of cell
      death that results from abnormal mitosis, which does not seem to depend on wild
      type p53. Sometimes mitotic catastrophe is used restrictively for faulty mitosis
      leading to cell death, which may occur via apoptosis or necrosis. We critically
      review herein how antitumor therapy may elicit the response of human cancers
      through different cell pathways leading to cell death.

PMID- 19856650
TI  - Non-pegylated liposomal doxorubicin in combination with cyclophosphamide or
      docetaxel as first-line therapy in metastatic breast cancer: a retrospective
      analysis.
AB  - AIMS AND BACKGROUND: Anthracyclines such as doxorubicin play a central role in
      the management of advanced breast cancer. Unfortunately, the clinical benefits of
      anthracyclines are limited by cardiotoxicity that can lead to the development of
      potentially fatal congestive heart failure. In order to limit anthracycline
      related cardiotoxicity, liposomal formulations of doxorubicin have been
      developed. This retrospective analysis evaluated the experience obtained with non
      pegylated liposomal doxorubicin as first-line therapy in 34 patients with
      metastatic breast cancer. METHODS: Patients received non-pegylated liposomal
      doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n
      = 20) for up to eight cycles, and efficacy and safety were assessed according to
      standard criteria. RESULTS: The overall response rate was 71%. The median
      progression-free survival was 8 months in patients receiving non-pegylated
      liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving
      non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly
      observed toxicities were grade 1-2 leucopenia, alopecia, nausea and vomiting; no
      grade 3-4 toxicities were observed. Overall, three patients (9%) experienced
      grade 1 cardiac toxicity. CONCLUSIONS: Our results support the use of non
      pegylated liposomal doxorubicin as an alternative to conventional doxorubicin
      formulations in combination regimens for the first-line therapy of metastatic
      breast cancer.

PMID- 19856651
TI  - Docetaxel and gemcitabine in the treatment of metastatic breast carcinoma: a dose
      finding study.
AB  - AIMS AND BACKGROUND: Patients with metastatic breast cancer previously treated
      with anthracyclines for advanced disease are usually refractory to any further
      treatment with anthracyclines and have a poor prognosis. Therefore, new drugs or
      new combinations of drugs are needed. One approach has been to focus on the type
      of chemotherapy with low toxicity that preserves quality of life during
      treatment, such as weekly drug administration. STUDY DESIGN: We designed a dose
      finding study to determine the maximum tolerated dose of gemcitabine plus
      docetaxel, given on a weekly schedule in metastatic breast cancer previously
      treated with anthracyclines. Three escalating doses of gemcitabine (900, 1000 and
      1100 mg/m2) on days 1 and 8 in combination with a fixed dose of docetaxel, 35
      mg/m2 on days 1 and 8 were planned. Dose-limiting toxicity included grade > 3
      hematologic toxicity, grade > 2 stomatitis, asthenia, diarrhea or organ-specific
      toxicity (except alopecia). Dose escalation was stopped if 1 out of 3 patients at
      any dose level experienced dose-limiting toxicity. RESULTS: Nine patients
      received a mean of 5.1 (range, 1-9) cycles. Gastrointestinal and leukopenia were
      the main dose-limiting toxicity. No patient experienced dose-limiting toxicity at
      dose level 1; at dose level 2, 2 out of 3 patients had dose-limiting toxicity and
      3 additional patients treated at dose level 2 confirmed that the maximum
      tolerated dose had been reached. CONCLUSIONS: The recommended gemcitabine dose in
      combination with docetaxel (35 mg/m2 for a phase II study) was established at 900
      mg/m2.

PMID- 19856652
TI  - A pilot study of irinotecan combined with 5-fluorouracil and leucovorin for the
      treatment of Chinese patients with locally advanced and metastatic gastric
      cancer.
AB  - AIMS AND BACKGROUND: The FOLFIRI regimen was evaluated for its anti-tumor
      activity and toxicity in Chinese patients with locally advanced and metastatic
      gastric cancer. METHODS AND STUDY DESIGN: Treatment consisted ofirinotecan, 180
      mg/m2 (90-min infusion), leucovorin, 200 mg/m2 (2-h infusion), followed by 5
      fluorouracil, 400 mg/m2 (bolus), and then 5-fluorouracil, 600 mg/m2 (22-h
      continuous infusion) on days 1 and 2, every 14 days. RESULTS: Twenty-six
      patients, of whom 17 were pretreated, were included in the study. Partial
      response was observed in 9 patients (37.5%). The overall disease control rate was
      83.3%. Median progression-free and overall survival was 6.8 and 11.2 months,
      respectively. Grade 3-4 neutropenia was observed in 6 patients (23.1%) and grade
      2-3 diarrhea in 5 (19.2%). No treatment-related deaths occurred. CONCLUSIONS: The
      results demonstrate that the FOLFIRI regimen is an active regimen with acceptable
      toxicity for Chinese patients with advanced and metastatic gastric cancer that
      merits further investigation in comparative trials.

PMID- 19856653
TI  - Laparotomy with a curative intent in patients with suspected locally recurrent
      gastric cancer.
AB  - AIMS AND BACKGROUND: Most recurrent gastric tumors are unsuitable for further
      resection or palliative surgery. The aim of the present study was to evaluate the
      role of re-resection in patients with local-regional recurrences of gastric
      cancer. METHODS AND STUDY DESIGN: Between 1998 and 2007, 26 patients underwent
      laparotomy for local-regional gastric cancer recurrence. Length of time to
      recurrence, recurrence patterns, operative procedures, morbidity, mortality and
      survival after re-resection were evaluated. RESULTS: Re-resection was possible in
      13 patients (50%). Among patients with resectable tumors, survival times were
      markedly longer, with 2 patients reaching 60 months of survival and 2 other
      patients reaching 48 and 28 months, respectively. Among patients with early
      recurrence, peritoneal carcinomatosis was more common. After re-resection,
      morbidity and mortality were seen, each in one patient. CONCLUSIONS: Most of the
      re-resected recurrences were intraluminal. In patients with early recurrences of
      gastric cancer, peritoneal carcinomatosis was encountered most frequently. Re
      resection was beneficial and long-term survival was achieved after re-resection.

PMID- 19856654
TI  - Surgery and radiotherapy in the treatment of malignant parotid tumors: a
      retrospective multicenter study.
AB  - AIMS AND BACKGROUND: Major salivary gland cancers are rare, with many histologic
      types and subtypes. The low incidence and heterogeneity of primary parotid
      carcinomas makes their outcome difficult to evaluate. Treatment remains primarily
      surgical, but optimal therapeutic regimens have yet to be fully realized. The
      present study reviews the experience of three Italian institutions in the
      treatment of primary parotid carcinomas in order to describe the
      clinicopathological presentation and treatment options with emphasis on
      radiotherapy and to analyze the factors influencing survival. METHODS AND STUDY
      DESIGN: The records of 110 patients with primary parotid neoplastic lesions
      treated at three Italian institutions from 1993 to 2004 were retrospectively
      reviewed. Six patients were excluded from the study: 3 received surgery alone and
      3 were not assessable, for a total of 104 assessable patients. Acute and late
      toxicity of radiotherapy was quantified following the recommendations of the
      RTOG/EORTC. Survival was analyzed by the actuarial Kaplan-Meier product-limit
      method. The influence of selected factors on 10-year disease-specific survival
      was analyzed. RESULTS: The 104 assessable patients were treated as follows: 11
      patients received radiotherapy as their only treatment (3 with a palliative
      purpose) and 93 had postoperative radiotherapy. Thirty-two patients underwent
      neck dissection: neck lymph node metastases were found in all them. Their mean
      age was 60 years (range, 14-92). According to the UICC/2002 TNM Classification, 8
      patients were stage I, 19 stage II, 34 stage III, 25 stage IVA, 5 stage IVB, 3
      recurrent and 10 not assessable (Tx). The most frequent histologies were adenoid
      cystic carcinoma (n = 16), mucoepidermoid carcinoma (n = 15), and acinic cell
      carcinoma (n = 15). Twenty-three patients had recurrences: 10 had local
      recurrences, 3 neck recurrences, 9 distant metastases, and 1 patient had both
      local recurrence and distant metastases. No factors were observed that would
      negatively influence the prognosis. Actuarial 10-year disease-specific survival
      was 71% and actuarial 10-year local control 82%. CONCLUSIONS: The treatment of
      salivary gland malignancies remains primarily surgical. Our study confirms the
      results of the literature with surgery and adjunctive radiotherapy in patients
      with advanced-stage disease. No variables were observed to influence the
      prognosis.

PMID- 19856655
TI  - Three-fraction stereotactic body radiation therapy for isolated liver recurrence
      from colorectal cancer.
AB  - AIMS: To determine the feasibility and efficacy of 3-fraction stereotactic body
      radiation therapy for isolated colorectal cancer liver metastases. MATERIALS AND
      METHODS: Ten patients with isolated inoperable liver metastasis from colorectal
      cancer with progression after salvage chemotherapy underwent stereotactic body
      radiation therapy. Follow-up was 7-49 months (median, 12). Six patients had a
      solitary lesion and 4 patients had 2 lesions. Internal target volumes of
      metastatic liver tumors ranged from 3.4 to 271 ml. Stereotactic body radiation
      therapy doses ranged from 36 to 51 Gy and were administered in three fractions.
      All patients demonstrated disease progression despite chemotherapy prior to
      stereotactic body radiation therapy. RESULTS: Three-year overall survival and
      local control rates were 40% and 60%, respectively. Tumors with an internal
      target volume < 100 ml showed better local control rate than larger tumors. No
      severe complication was attributed to the therapy. CONCLUSION: Our study suggests
      the potential feasibility of stereotactic body radiation therapy for selected
      patients with colorectal cancer liver metastasis and no treatment option. The
      study showed that excellent local control was achieved in patients with a total
      tumor volume of < 100 ml but failed to clarify the role of stereotactic body
      radiation therapy for larger tumors. Further large scale studies are needed to
      define the indications of such therapy.

PMID- 19856656
TI  - Postoperative accelerated radiotherapy with cytoprotection followed by three
      dimensional conformal boost in patients with early endometrial/cervical cancer.
AB  - AIMS AND BACKGROUND: Adjuvant external beam radiotherapy is highly recommended
      for uterine carcinomas invading beyond the inner half of the myometrium or
      cervical stage IIa carcinomas. The addition of a booster intracavitary dose is
      widely used. METHODS: We assessed the feasibility and toxicity of a
      hypofractionated accelerated conformal radiotherapy scheme (2.7 Gy per fraction,
      for 14 consecutive fractions to the pelvis) supported with the cytoprotective
      agent amifostine (HypoARC). The amifostine dose was individualized (500-1000 mg
      daily subcutaneously). A booster dose of radiation was given to the vagina and
      stump using a 6-field 3D-conformal technique (3 x 4 Gy or 4 x 3 Gy) instead of
      intracavitary radiotherapy. RESULTS: Grade 2 diarrhea appeared in 9/25 (36%) and
      grade 1 cystitis in 7/25 (28%) cases. Analysis according to the amifostine dose
      level clearly showed reduced toxicity in patients receiving a daily dose of 750
      1000 mg (P < 0.009). Within a median follow-up of 31 months (range, 11-52), there
      was only one case with grade 2 colitis (the patient had received no amifostine).
      None of the patients treated has relapsed locally or to distant organs within a
      median of 31 months of follow-up. CONCLUSIONS: It is concluded that HypoARC
      followed by 3D-conformal booster dose to the vagina is feasible and convenient
      for patients and for busy radiotherapy departments, as it reduces the overall
      time by 50%. When supported by high-dose daily amifostine, it has an impressively
      low rate of early and late radiation toxicity.

PMID- 19856657
TI  - Assessment of influence of smoking, drinking, leukoplakia and dental irritation
      on local control of early oral tongue carcinoma treated with brachytherapy: age
      and dental factors are potential prognostic factors.
AB  - BACKGROUND: To examine the background characteristics of elderly patients (65
      years or older) with node-negative mobile tongue cancer (T1-2N0M0) who showed
      worse local control than a younger group. MATERIALS AND METHODS: We
      retrospectively analyzed background data for 265 patients treated with
      brachytherapy with or without external radiotherapy between 1967 and 1999. We
      examined dental factors (such as irritation by prosthesis), leukoplakia, tobacco
      smoking and alcohol consumption for comparisons between the elderly (age > or =
      65 years; n = 83) and a control group (64 years or younger; n = 182). RESULTS:
      The elderly patients showed a worse outcome than the control group (respectively
      86% and 70% at 5 years; P < 0.05). Incidence of dental factors tended to be
      higher for elderly patients (53%) than the control group (40%, P = 0.07). Dental
      factors proved to have prognostic importance for local control. Five-year local
      control rate was 85% for patients with and 76% for patients without dental
      factors (P = 0.04). The elderly group positive for dental factors showed a lower
      5-year local control rate (61%) than the other three groups [(elderly without the
      dental factor (-) group (80%), control with the dental factor (+) group (84%),
      and control without the dental factor (-) group (87%)] (P < 0.05). Leukoplakia
      was found more frequently in the control (23%) than in the elderly group (5%) (P
      = 0.006) but had no effect on treatment outcome. CONCLUSIONS: Age and dental
      factors (including prosthesis irritation) are potentially important prognostic
      factors for local control of oral tongue cancer treated with brachytherapy,
      especially for elderly patients.

PMID- 19856658
TI  - Quality assurance of a record-and-verify system.
AB  - AIMS AND BACKGROUND: With the introduction of more complex three-dimensional
      conformal radiotherapy and intensity-modulated radiotherapy techniques in
      clinical practice, the use of record-and-verify systems is recommended to improve
      the accuracy of radiotherapy treatments. The aim of the present study was to
      evaluate, for a commercial record-and-verify system, the efficiency, integration
      with the treatment planning system, and impact of manual checking of data. The
      most frequent errors or misses were also evaluated. MATERIALS AND METHODS: The
      development of internal protocols to systematically implement new technologies
      has been identified as a priority in the departmental quality assurance process.
      Data electronically fed into the record-and-verify system were compared with
      those manually recorded in the clinical paper chart over a period of almost 6
      years (October 2000 to December 2006). A total of 7768 treated patients was
      reviewed. The check was performed by using a homemade data base in which the
      errors are stratified as follows: 1) general section, 2) geometric and dosimetric
      section, and 3) delivered dose section. RESULTS: On a total of 7768 checked
      patients, one or more mismatches between treatment planning system data and
      record-and-verify system data or paper chart data were observed for 452 patients
      (5.8% of total number of inspected patients). The percentage of discrepancies out
      of the total was: 2.2% in the general section, 3.3% in the dosimetric and
      geometric section, and 4.2% in the delivered-dose section. CONCLUSIONS: Although
      record-and-verify systems assume a crucial role in the accuracy and
      reproducibility of radiation treatment, their inability to eradicate all the
      errors requires vigilance on the part of the radiation therapy and physics team.

PMID- 19856659
TI  - Decreased serum levels of carboxylesterase-2 in patients with ovarian cancer.
AB  - AIMS AND BACKGROUND: Carboxylesterase-2 has been identified as the key enzyme in
      the metabolic activation ofirinotecan, a topoisomerase I inhibitor commonly used
      in the treatment of many solid tumors. Previous studies have shown that
      carboxylesterase-2 is down-regulated in colorectal cancer following progression
      of the disease. However, very limited information is available on
      carboxylesterase-2 expression in ovarian cancer. The aim of the present study was
      to detect the serum level and the tissue expression of carboxylesterase-2 in
      human ovarian cancer patients at different stages of the disease. METHODS:
      Carboxylesterase-2 levels in the serum of ovarian cancer patients were
      investigated by western blot and ELISA and in the tumor mass of ovarian cancer
      patients by western blot. RESULTS: Both the serum carboxylesterase-2 level and
      the expression of carboxylesterase-2 in tumor tissues were significantly
      different among patients at different stages of the disease (n = 40). No positive
      correlation was found between the serum carboxylesterase-2 level and the cancer
      antigen 125 level (n = 40). Serum carboxylesterase-2 is more sensitive than
      cancer antigen 125 in detecting the early stage patient with ovarian cancer.
      CONCLUSIONS: Our results indicate that serum carboxylesterase-2 level might be a
      potential marker in the diagnosis of the early stage ovarian cancer.

PMID- 19856660
TI  - Serotonin transporter 5-HTTLPR polymorphism and response to citalopram in
      terminally ill cancer patients: report of twenty-one cases.
AB  - The aim of this study was to examine the effects of the SSRI antidepressant drug
      citalopram on anxiety, depression and mental adjustment to cancer in terminally
      ill cancer patients, considering also the 5-HTTLPR genetic polymorphism. A group
      of twenty-one consecutive patients admitted to the hospice of the Casa di Cura
      Pineta del Carso (Trieste, Italy) with different types of advanced cancer, who
      were clinically judged to require treatment with an antidepressive drug, was
      treated with citalopram for two weeks. The response was determined and related to
      5-HTTLPR. Citalopram significantly reduced the scores on the depression and
      anxiety subscales of the Hospital Anxiety and Depression Scale (HADS). When the
      effects of citalopram were analyzed in relation to the 5-HTTLPR polymorphism, the
      HADS depression score was significantly decreased only in patients with the "l/l"
      allelic variant of the serotonin transporter conferring high functional activity,
      while the score of the Mini-MAC fatalism scale was significantly increased in
      patients carrying at least one "s" allele. These preliminary findings seem to
      indicate that two weeks of treatment with citalopram are effective in reducing
      depressive symptoms in terminally ill cancer patients. Moreover, the effects of
      citalopram on fatalism as a strategy of mental adaptation to cancer, and on
      depressive symptoms depend on the allelic variants of the 5-HTTLPR genotype of
      the patients. These results seem to encourage the examination of a larger patient
      sample and of different treatment schedules, as well as a more thorough
      characterization of fatalism as a coping strategy in cancer patients.

PMID- 19856661
TI  - Persistent hypercalcitoninemia in patients with medullary thyroid cancer.
AB  - Medullary thyroid carcinoma is a highly malignant and progressive disease.
      Surgery is the only effective treatment. Calcitonin is a significant marker for
      medullary thyroid carcinoma, and due to its sensitivity it represents a useful
      tool for the follow-up. The outcome of patients affected by medullary thyroid
      carcinoma depends on tumor size, lymph node involvement, and adequacy of primary
      surgical management. In the present study, the authors reviewed their own
      experience in the cure of medullary thyroid carcinoma. Forty-one patients
      operated for sporadic medullary thyroid carcinoma were included. Indications for
      surgery, inclusive of lymphectomy techniques, timing of redo surgery, and the
      meaning of calcitonin levels in highlighting disease are extensively discussed.
      Patients with elevated calcitonin levels and favorable outcome are considered,
      together with the various diagnostic tools to be employed during patient workup.

PMID- 19856662
TI  - Loss of heterozygosity combined with promoter hypermethylation, the main
      mechanism of human MutL Homolog (hMLH1) gene inactivation in non-small cell lung
      cancer in a Chinese population.
AB  - AIMS AND BACKGROUND: The mechanism of human MutL Homolog (hMLH1) gene
      transcriptional inactivation in non-small cell lung cancer (NSCLC) is still
      unclear. The aim of this study is to further investigate the main mechanism of
      hMLH1 gene inactivation in NSCLC samples of Chinese patients. METHODS AND STUDY
      DESIGN: This study was performed in surgically resected primary tumor and matched
      normal tissues from 116 NSCLC cases. The hMLH1 gene alterations examined included
      loss of heterozygosity (LOH) by D3S1612 locus PCR-electrophoresis-silver staining
      and promoter methylation by HpaII/ MspI-based PCR analysis. Loss of hMLH1 mRNA
      expression was analyzed by reverse transcription-polymerase chain reaction (RT
      PCR) and loss of hMLH1 protein expression was studied by immunohistochemistry and
      Western blot. RESULTS: The frequencies of LOH and promoter hypermethylation of
      the hMLH1 gene were 68.1% (79/116) and 72.4% (84/116), respectively. Among the 79
      hMLH1 LOH (+) cases, 68 (86.1%) showed hypermethylation, which was significantly
      higher than in the LOH (-) group. The frequencies of loss of hMLH1 mRNA
      expression and protein expression in NSCLC were 79.3% (92/116) and 76.7%
      (89/116), respectively. The frequency of 2-hit inactivation of hMLH1, 75.3%
      (67/89), by LOH combined with promoter hypermethylation was related to the loss
      of protein expression. CONCLUSIONS: Biallelic inactivation of the hMLH1 gene by
      LOH combined with promoter hypermethylation is likely to cause inactivation of
      hMLH1 protein and to play an important role in the development of NSCLC in the
      Chinese population.

PMID- 19856663
TI  - Changes in expression of bile canalicular CD10 and sinusoidal CD105 (endoglin) in
      peritumoral hepatic tissue.
AB  - AIMS AND BACKGROUND; Hepatic tissues, including bile canaliculi and sinusoids,
      around primary or metastatic tumors are destructed and regenerate associated with
      tumor growth, and may show some phenotypic changes. The present study was
      undertaken to examine the expression of CD10 in bile canaliculi [CD10(BC)] and
      CD105 (endoglin) along hepatic sinusoids [CD105(HS)] in peritumoral hepatic
      tissue (PTH). METHODS: Fifty samples of resected liver bearing hepatocellular
      carcinoma (HCC) or metastatic carcinoma were immunostained for CD10 and CD105.
      The immunoreactivity for CD10(BC) and CD105(HS) in the background hepatic tissue
      of tumors and PTH was scored separately. RESULTS: CD10(BC) was moderately or
      markedly expressed in the background hepatic tissue without chronic hepatitis or
      cirrhosis in most of the cases, and was significantly downregulated in chronic
      hepatitis and cirrhosis. CD105(HS) was negative or minimally positive in most of
      the cases of hepatic tissue bearing metastatic carcinoma, and showed a
      significant increase in chronic hepatitis and cirrhosis. Compared with the
      background, PTH revealed significantly decreased CD10(BC) staining irrespective
      of HCC or metastatic carcinoma, and showed belt-like CD105(HS) expression in
      66.7% of the cases of metastatic carcinoma and in 88.6% of those with HCC.
      CONCLUSIONS: These data indicate that the expression patterns of CD10(BC) and
      CD105(HS) in PTH are similar to those in chronic hepatitis and cirrhosis, which
      may be caused by persistent injury and resultant regeneration of hepatic tissue.

PMID- 19856664
TI  - Pitfalls in the diagnosis of neuroendocrine tumors: atypical clinical and
      radiological findings as cause of medical mistakes.
AB  - AIMS AND BACKGROUND: Carcinoids are infrequent neoplasms arising from
      neuroendocrine cells. Due to blurred symptoms and the presence of equivocal
      diagnostic findings, these tumors are sometimes misdiagnosed. Therefore,
      increased rates of false neuroendocrine tumors represent an emerging problem in
      clinical practice. Our aim is to alert clinicians on this matter by supplying
      them with useful warnings. METHODS: In the specialized neuroendocrine tumor study
      Center Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori
      Neuroendocrini (Ce.Ri.Ca), some patients highly suspected to have a
      neuroendocrine tumor have been recognized as having false neuroendocrine tumors.
      The related clinical and instrumental findings leading to a previous wrong
      neuroendocrine tumor diagnosis are reported. RESULTS: From July 2006 to December
      2008, 88 consecutive cases of neuroendocrine tumors (Nets) were referred at
      Ce.Ri.Ca. In the former group, 8 cases of false Nets were discovered while in the
      remaining 80 cases a correct Net diagnosis was carried out. Watchful differential
      diagnoses and skill appraisal of laboratory investigations resulted in: chronic
      atrophic gastritis with enterochromaffin-like cell hyperplasia (4 cases),
      estrogen-deprivation syndrome (1), hypochondriac disorder (1), metabolic syndrome
      (1), and sarcoidosis (1). CONCLUSIONS: Neuroendocrine tumors are still relatively
      known clinical entities. To discriminate false neuroendocrine tumors from
      neuroendocrine tumors requires a good expertise and a large daily practice with
      the disease. Good knowledge and skillfulness in identifying biochemical
      alterations and false radiological positive results could avoid both patient
      inconvenience and very expensive workup. The importance of a multidisciplinary
      approach in specialized centers is emphasized.

PMID- 19856665
TI  - Chemopreventive effect of a novel nutrient mixture on lung tumorigenesis induced
      by urethane in male A/J mice.
AB  - AIMS AND BACKGROUND: Lung cancer, a leading cause of cancer death, is associated
      with exposure to inhalation carcinogens, most commonly those found in tobacco
      smoke. We investigated the in vivo effect of dietary supplementation with a
      nutrient mixture containing lysine, proline, arginine, ascorbic acid, green tea
      extract, N-acetyl cysteine, selenium, copper and manganese on the development of
      urethane-induced lung tumors in male A/J mice. METHODS: After one week of
      isolation, seven-week-old male A/J mice (n = 25) weighing 17-19 g were randomly
      divided into three groups: group A (n = 5), group B (n = 10), and group C (n =
      10). Mice in groups B and C were each given a single intraperitoneal injection of
      urethane (1 mg/g body weight) in saline, whereas group A mice received an
      injection of saline alone. Groups A and B were fed a regular diet, whereas group
      C was fed the same diet supplemented with 0.5% nutrient mixture. After 20 weeks,
      mice were sacrificed, lungs were excised and weighed, and tumors were counted and
      processed for histology. RESULTS: Urethane-challenged mice developed tumors.
      However, the mean number of tumors and the mean lung weights in the mice on the
      supplemented diet were significantly reduced, by 49% (P < 0.0001) and 18% (P =
      0.0025), respectively, compared to mice on the control diet. We observed neither
      significant differences in body weight gains nor in diet consumption among the
      mice. Pulmonary lesions were morphologically similar for both the groups
      (adenomas), but lesions were smaller in the test group. CONCLUSIONS: The results
      suggest that nutrient mixture has inhibitory potential on the development of
      mouse lung tumors induced by urethane.

PMID- 19856666
TI  - Tailgut cyst, an unusual cause of pseudomyxoma peritonei.
AB  - BACKGROUND: Retrorectal hamartoma, also known as tailgut cyst, is a rare tumor
      that arises from remnants of the embryonic postanal gut. The tumor occurs in the
      retrorectal space and may undergo malignant degeneration. METHODS: The clinical
      information on a single patient with pseudomyxoma peritonei associated with a
      tailgut cyst was reviewed and a literature review of the subject performed.
      RESULTS: In this patient there was malignant degeneration of a tailgut cyst
      localized to the pelvis. Twenty months later a local recurrence in the pelvis and
      pseudomyxoma peritonei widely distributed in the abdomen were successfully
      treated by cytoreductive surgery and perioperative chemotherapy. CONCLUSION;
      Tailgut cyst may, if resected with tumor spillage, result in pseudomyxoma
      peritonei. Our treatment--which has maintained a disease-free status for one year
      -was cytoreductive surgery plus perioperative chemotherapy.

PMID- 19856667
TI  - Coexistent malignant melanoma and renal cell carcinoma.
AB  - Patients with malignant melanoma are at an increased risk of developing
      subsequent primary melanomas and also nonmelanoma cutaneous cancers. Several
      studies have reported an association between malignant melanoma and breast
      cancer, bladder cancer, colorectal cancer, neuroectodermal tumours, non-Hodgkin's
      lymphoma, leukaemia and renal cell carcinoma. We report a case series of patients
      with a diagnosis of malignant melanoma who also developed a renal mass. In two of
      these cases, the renal mass became apparent on diagnostic imaging as part of the
      staging investigations at the time of initial diagnosis of the malignant
      melanoma. In both of these cases, biopsy of the renal mass confirmed the presence
      of a separate primary renal cell carcinoma which had presented concurrently with
      the malignant melanoma. A third case presented with bone metastases ten years
      after excision of a thin melanoma. Further imaging revealed pulmonary metastases
      and a renal mass, biopsy of which confirmed renal cell carcinoma. In contrast, a
      fourth patient underwent a right nephrectomy for a renal mass having presented
      with abdominal discomfort. The histology of this lesion was in keeping with
      metastatic melanoma, and the patient's past history included a diagnosis of
      ocular melanoma eight years prior to the development of metastatic disease in the
      right kidney. Survival rates for patients with many types of malignant disease
      are improving, and there have been significant advances in clinical imaging
      techniques. Consequently the development and detection of a second primary
      cancer, either presenting concurrently or on subsequent follow-up, is likely to
      be increasingly observed. The series of patients reported here highlights the
      importance of a diagnostic biopsy in patients with malignant melanoma who develop
      a renal mass in order to establish a diagnosis and to plan optimal treatment.

PMID- 19856668
TI  - Late tonsil metastases from renal cell cancer: a case report.
AB  - The occurrence of renal carcinoma metastasis to the head and neck region is
      extremely rare. Some authors have reported metastasis of renal cell carcinoma to
      the parotid glands, nose and paranasal sinus, tongue, larynx, thyroid and
      palatine tonsil. In this report we describe a rare case of renal cell cancer
      metastasized to the right tonsil in a 76-year-old man with previously diagnosed
      bone and lung metastases. To the best of our knowledge this is the first
      documented example of radiotherapy treatment in this type of presentation.
      Radiotherapy was effective in treating the lesion with satisfactory functional
      results.

PMID- 19856669
TI  - Primary peritoneal malignant mixed mesodermal (Mullerian) tumor.
AB  - AIMS AND BACKGROUND: Malignant mixed mesodermal tumor (MMMT) is a biphasic
      neoplasm (carcinosarcoma) composed of both epithelial and mesenchymal elements.
      Extragenital MMMT, including primary peritoneal MMMT, is an extremely rare tumor
      with features consistent with its origin from the secondary Mullerian system. The
      neoplastic elements of extragenital MMMT presumably arise directly from the
      mesothelium or submesothelial stroma and hence parallel the biphasic pattern of
      the genital (uterine or ovarian) counterpart. METHODS AND STUDY DESIGN: Here we
      report on the clinical, pathological, and immunohistochemical features of a case
      of peritoneal MMMT in a 65-year-old woman. The patient presented with abdominal
      fullness and pain. Gynecological examination revealed a huge pelvic abdominal
      mass. On histology, the tumor consisted of poorly differentiated carcinomatous
      and sarcomatous (rhabdomyosarcoma) components. Further immunohistochemical
      analysis revealed positive reactivity for both epithelial (cytokeratin and
      epithelial membrane antigen) and mesenchymal (vimentin, S-100, and desmin)
      markers. The patient refused treatment and died of the disease three months
      later. RESULTS AND CONCLUSIONS: Based on the present case and on previous
      studies, primary peritoneal MMMT seems to be a rare but highly malignant neoplasm
      with an aggressive behavior and poor prognosis. Its exact origin, histogenesis
      and molecular alterations are poorly understood.

PMID- 19856670
TI  - MRI features of cotyledonoid dissecting leiomyoma of the uterus.
AB  - Imaging evaluation of uterine masses is important to assess the type of lesion
      and to target surgery, if surgical excision is necessary. This can be decisive in
      fertile women with benign masses resembling malignancies, in order to avoid
      overtreatment. In this study, the magnetic resonance imaging (MRI) appearance of
      cotyledonoid dissecting leiomyoma of the uterus, a rare benign variant of
      leiomyoma mimicking malignancy, is presented.

PMID- 19856671
TI  - 3p abnormalities in peripheral lymphocytes in small cell lung cancer.
AB  - 3p abnormalities are the most frequent chromosome abnormalities in small cell
      lung cancer (SCLC). To date these abnormalities have only been observed in cells
      derived from tumor tissues. It is thought that cancer-related chromosome
      abnormalities in peripheral lymphocytes could help to predict cancer development,
      prognosis, and future metastasis. We report clonal and nonclonal 3p abnormalities
      in the peripheral lymphocytes of two patients with SCLC. A standard T-lymphocyte
      culture method and GTL banding technique were applied to the samples, and various
      clonal and nonclonal chromosome 3 abnormalities, i.e., -3, del(3)(p24),
      del(3)(p21), del(3)(p11), del(3)(q22), inv(3)(p14q29), and inv(3)(q21q29) were
      observed. Efforts have been made to understand if there are cancer-related
      chromosome abnormalities in lymphocytes and the suitability of these
      abnormalities to predict cancer development or metastases. As far as we know,
      this is the first report on chromosome 3 abnormalities in lymphocytes. Since 3p
      abnormalities are specific for SCLC, it is important to show that these cancer
      related abnormalities can be found in blood cells.

PMID- 19856672
TI  - Perianal granular cell tumor: report of a case and review of the literature.
AB  - INTRODUCTION: Granular cell tumor was first described by Abrikossoff in 1926.
      Over the years several cases of this neoplasm have been reported, with a variety
      of localizations. We here report a case of perianal granular cell tumor and
      discuss its histogenesis and its relevance to clinical practice. METHODS: The
      clinical course and histopathology of the case are reviewed, and a literature
      search for other reported cases has been performed. RESULTS: A 46-year-old woman
      presented with a perianal nodular lesion. Pathological examination revealed a
      granular cell tumor. A literature search produced only 25 other cases of anal and
      perianal granular cell tumors. CONCLUSIONS: Granular cell tumors are rarely
      observed in the perianal region. Their existence must always be borne in mind in
      the differential diagnosis of perianal neoplasms. In most cases surgical excision
      is curative, but potential malignant transformation must be considered during
      therapeutic procedures and follow-up.

PMID- 19856673
TI  - Use of sorafenib in two metastatic renal cell cancer patients with end-stage
      renal impairment undergoing replacement hemodialysis.
AB  - Patients with renal cell carcinoma (RCC) may exhibit renal impairment as a more
      or less direct consequence of their primary disease. Renal impairment may become
      a severe complication and alter the normal pharmacokinetic and pharmacodynamic
      behavior of treatment drugs, thus increasing the risk of side effects. We will
      discuss the cases of two advanced RCC patients with end-stage renal impairment
      submitted to dialysis who were treated with sorafenib tosylate in our center. Our
      experience confirms the scarce literature data available so far that indicate
      that sorafenib can be used in patients undergoing dialysis. Dialysis cannot be
      considered per se a contraindication to sorafenib therapy, which can be
      effective. However, patients must be carefully selected and monitored, since
      sorafenib administration unquestionably increases the risk of side effects in
      patients affected by several conditions.

PMID- 19856674
TI  - Ifosfamide encephalopathy and use of methylene blue. A case report of different
      sequential neurotoxicity.
AB  - Neurotoxicity is a clinically relevant adverse event observed with the use of
      ifosfamide. It is usually mild, occasionally severe and seldom fatal. Ifosfamide
      induced encephalopathy requires interruption of chemotherapy, intravenous
      hydration and administration of methylene blue. Less is known about the efficacy
      of methylene blue in avoiding a second episode of ifosfamide-induced
      encephalopathy while maintaining chemotherapy with ifosfamide. We report a case
      of a different clinical manifestation of ifosfamide-induced encephalopathy after
      continued ifosfamide use and despite methylene blue in a patient with
      retroperitoneal sarcoma.

PMID- 19856675
TI  - Gemcitabine-induced supraventricular tachycardia.
AB  - The superior toxicity profile is one of the major reasons for the widespread use
      of gemcitabine in cancer treatment. Bone marrow suppression is the most common
      side effect, while non-hematological events are relatively infrequent. Cardiac
      toxicity is a rare complication and cardiac arrhythmia is even rarer. We report
      the case of a 67-year-old woman with metastatic breast cancer without a history
      of cardiac arrhythmia or ischemic heart disease who developed supraventricular
      tachycardia. The symptoms had started immediately after gemcitabine treatment.
      The arrhythmia responded poorly to common treatment and was eventually controlled
      by oral propranolol five days after admission. The present case suggests that
      supraventricular tachycardia may be triggered by gemcitabine even without
      underlying significant heart disease and may be resistant to conventional
      therapy.

PMID- 19856676
TI  - Adaptive radiation therapy in a patient with a massive nodal breast cancer
      recurrence.
AB  - Adaptive radiation therapy (ART) is the next improvement in image-guided
      radiation therapy (IGRT). ART consists in changing treatment delivery to
      compensate for changes in patient anatomy or tumor volume. The treatment planning
      is therefore adapted to the new target volume. By daily imaging, the tumor volume
      can be assessed and compared with the initial volume. In case of tumor
      progression or tumor response, a new plan can be obtained to adequately treat the
      new volume. We report the use of ART with the Plan Adaptive software of
      TomoTherapy Inc. in a patient with massive breast cancer recurrence in the
      axilla. Between the CT simulation and the first day of radiotherapy the axillary
      lesion progressed. Megavolt CT performed to image-guide the treatment showed
      impressive growth of the lesion, which went out of the treatment field. By
      studying the dose distribution on the new anatomy, we found that the planning
      target volume was substantially undercovered by the prescription dose. Adaptive
      planning was performed using the anatomical information acquired by the megavolt
      CT.

PMID- 19856677
TI  - Salvage high dose rate brachytherapy after primary external beam irradiation in
      localized prostate cancer: a case report.
AB  - No standard treatment exists for locally relapsed prostate cancer after primary
      external beam radiotherapy with no evidence of distant metastases. Radical
      prostatectomy, brachytherapy, cryotherapy and high-intensity focused ultrasound
      are currently used as local salvage treatments. Data on the safety and
      effectiveness of high dose rate (HDR) brachytherapy in this scenario are limited.
      We report on a patient who has no evidence of disease and no late urinary or
      gastrointestinal toxicity 33 months after receiving HDR treatment for recurrent
      prostate cancer.

PMID- 19856679
TI  - Important role of gemcitabine in the treatment of classic Kaposi's sarcoma.

PMID- 19856678
TI  - Fulminant liver failure in a patient affected by polycystic liver disease and
      liver metastases from breast carcinoma.
AB  - BACKGROUND: Polycystic liver disease (PLD) is a rare, congenital, benign
      condition characterized by the presence of multiple bile-duct-derived epithelial
      cysts in the liver parenchyma. The disease is usually asymptomatic, but cyst
      growth can result in complications such as ascites, esophageal varices, jaundice
      and hepatic failure. The exact mechanism leading to cyst growth is unclear, but
      estrogenic stimulation and paracrine action of vascular endothelial growth factor
      (VEGF) are thought to play a role in the growth of cyst epithelium. CASE REPORT:
      We report a case of acute liver failure in a young woman with PLD and liver
      metastases from breast carcinoma. RESULTS: No data are available in the
      literature about metastatic liver involvement in PLD patients affected by breast
      cancer. The prognosis of patients with liver metastases is generally poor but
      fulminant liver failure is a very rare occurrence. Estrogen stimulation seems to
      be a risk factor for breast cancer and severe PLD. In the reported case, the
      presence of either the cysts or the metastatic lesions may have resulted in more
      extensive liver damage. CONCLUSIONS: The adoption of drugs selected in relation
      to their hepatic toxicity together with careful monitoring of liver function is
      warranted in the management of breast cancer patients affected by PLD, in order
      to reduce the risk of liver failure.

PMID- 19856680
TI  - Creating order. A quantitative analysis of psychiatric practice at the Swiss
      mental institutions of Burgholzli and Rheinau between 1870 and 1970.
AB  - This paper analyses the concepts of order and normality underlying the daily
      psychiatric practice of two Swiss mental health institutions between 1870 and
      1970, based on a representative random sample of 1330 patient records from the
      two state institutions in the Canton of Zurich. The quantitative analysis covers
      the types of psychiatric measure taken in these cases, as well as the rationales
      behind them. It is concluded that the order of the institution, of society and,
      above all, the order of gender played an important role in the choice and
      implementation of various measures.

PMID- 19856681
TI  - Encountering hysteria: doctors' and patients' perspectives on hysteria in
      Denmark, 1875-1918.
AB  - The history of hysteria stretches over several millennia and contains a plethora
      of different understandings and interpretations. This paper focuses on a central
      part of its Danish history, from the last decades of the nineteenth-century 'age
      of nervousness' until the end of World War I. It is argued that the understanding
      and negotiation of hysteria and its explanations took place in a complex
      interaction between doctors and their patients. Whereas the psychiatrists during
      this period moved towards an understanding of hysteria as a functional disorder,
      the patients, of whom approximately one-third were male, maintained that their
      illness was of somatic origin, and closely related to social, economic and
      working conditions.

PMID- 19856682
TI  - Bethlem's Irish: migration and distress in nineteenth-century London.
AB  - Association between migration and mental illness is widely reported. This study
      aimed to gain insight into the mental health of Irish migrants into Britain in
      the years 1843-53. Casebooks from the period were examined for Irish ethnicity,
      and clinical profiles were compared with those of age-matched control samples.
      Irish-born patients were found to have a greater proportion of diagnoses of mania
      than controls (p < or = 0.01). They were more likely to be admitted for 12 months
      or longer (p < or = 0.001) and more likely to receive religious attributions for
      illnesses by the treating physician. The more common diagnosis of mania in the
      Irish group can be explained in terms of the effects of migration, differences in
      idioms of distress, or in terms of prejudice.

PMID- 19856683
TI  - Emergency compulsory admissions in the Netherlands: fluctuating patterns in
      Rotterdam, 1929-2005.
AB  - This paper identifies the social changes and developments in public mental health
      that have contributed to fluctuations in the use of emergency compulsory
      admissions in Rotterdam, the Netherlands. Annual reports and administrative data
      over the years 1929-2005 indicate the impact of general and local factors.
      Demographic changes and statutory regulations were important general factors, but
      do not explain particular swings in the number of compulsory admissions. Key
      local factors were: the availability of alternative arrangements such as
      emergency centres and sheltered homes; an interpretation of the criteria for
      compulsory admissions shared by all disciplines involved; and better
      collaboration between services. These factors suggest that if the increasing use
      of compulsory admissions is to be reversed, a coordinated effort is needed.

PMID- 19856684
TI  - The abolition of capital punishment: contributions from two nineteenth-century
      Italian psychiatrists.
AB  - Capital punishment was the source of lively debate in Italy, from unification in
      1861 until 1888. The precedent for abolishing the death penalty had been set in
      Tuscany in 1786. This paper presents the arguments put forward by two eminent
      psychiatrists who opposed the death penalty, Carlo Livi and Andrea Verga. Livi
      set out his scientific case for abolition in two addresses given to the Accademia
      dei Fisiocritici in Siena in 1862. In 1889 Verga wrote a commentary on the Senate
      sitting and argued in favour of approving the Italian Penal Code. Verga agreed
      with Livi's arguments and disagreed with the School of Criminal Anthropology, led
      by Cesare Lombroso and Raffaele Garofalo, who were both in favour of capital
      punishment.

PMID- 19856685
TI  - [Education and training: road to the future in the development of anesthesiology
      for the 21st century].

PMID- 19856686
TI  - [Effects of changes in ion concentrations, osmolarity, and pH on recovery from
      atracurium- or vecuronium-induced neuromuscular blockade].
AB  - OBJECTIVES: To determine changes in sodium, potassium, calcium, magnesium and
      chloride ion concentrations in blood, osmolarity, and pH during surgery, and to
      assess the influence of such changes on atracurium- or vecuronium-induced
      neuromuscular blockade under inhaled or intravenous anesthesia. MATERIAL AND
      METHODS: Prospective study randomizing 119 ASA 1-2 patients; 52.1% of the
      patients received atracurium (26.8%, with isoflurane; 25.2%, with propofol) and
      47.9% received vecuronium (23.5%, with isoflurane; 24.3%, with propofol). The
      neuromuscular blockade was confirmed by electromyography of the adductor pollicis
      muscle (stimuli delivered to the cubital nerve). Two venous blood samples were
      extracted to measure ureic nitrogen, creatinine, glucose, ion concentrations
      (sodium, chloride, potassium, calcium, and magnesium), and osmolarity. Arterial
      blood gases and pH were also assessed. The first blood sample was extracted on
      inserting the venous catheter and the second on recovery of 25% of the first
      train-of-four twitch. RESULTS: The onset and duration of action for equipotent
      doses of atracurium and vecuronium were similar. Likewise, recovery was also
      similar. Plasma chloride ion and glucose levels tended to rise during surgery,
      while sodium, potassium and magnesium ion concentrations fell. Both total and
      effective plasma osmolarities also decreased. Fluid replacement therapy during
      surgery was at least partly responsible for these changes. Low calcium and
      magnesium concentrations and alkalosis prolonged some phases of atracurium
      recovery, while low sodium levels shortened the duration of some atracurium
      induced blockade recovery phases. The effect of changes in chloride ion
      concentrations on recovery was variable. High chloride, low calcium, and
      especially low sodium ion concentrations shortened some phases of the vecuronium
      induced blockade, while alkalosis prolonged its duration. CONCLUSIONS: Changes in
      electrolyte concentrations and pH as a result of standard fluid replacement
      therapy are moderate, well tolerated, and do not exercise a strong effect on the
      behavior of the neuromuscular blockade.

PMID- 19856687
TI  - [Failure of extension of epidural analgesia to anesthesia for emergency cesarean
      section].
AB  - Epidural analgesia provides effective control of labor pain and allows emergency
      cesarean section to be performed without recourse to general anesthesia. This
      technique is subject to failure, however. We sought to determine the incidence of
      failure of extension of epidural analgesia for labor to epidural anesthesia for
      emergency cesarean section. We also analyzed possible risk factors for failure. A
      2-month observational study was carried out in a tertiary-care university
      hospital in patients who had an epidural catheter inserted for labor analgesia
      and who later underwent emergency cesarean section. Epidural catheter failure was
      defined if additional analgesia was required during surgery or if general
      anesthesia was required. Data were gathered on possible risk factors, such as
      obesity, difficult epidural puncture, leakage of blood on insertion, history of
      cesarean delivery, need for rescue analgesia, and level of satisfaction with
      analgesia during dilation. In total, 134 emergency cesareans were performed in
      women carrying an epidural catheter. The catheter failed to administer the
      anesthetic in 18 patients (13.4%). General anesthesia was required in 9 cases
      (6.7%). Difficult insertion (more than 2 attempts) was associated with a higher
      failure rate (P=.064). The relative risk of epidural catheter failure was 2.86
      fold higher when rescue analgesia was needed during delivery than in cases when
      no supplement was required (P=.021). Receiving adequate analgesia during labor
      seems to be a protective factor (80%) against anesthetic catheter failure during
      cesarean section (P=.01). We conclude that high demand for rescue analgesia and
      signs of inadequate analgesia during labor should warn of epidural catheter
      failure if extension to anesthesia becomes necessary for a cesarean delivery.

PMID- 19856688
TI  - [Efficacy of a continuous infusion of local anesthetic into the surgical wound
      for pain relief after abdominal hysterectomy].
AB  - OBJECTIVE: To assess the quality of postoperative analgesia provided by
      intravenous administration of paracetamol and ketorolac plus morphine in bolus
      doses with or without continuous infusion of local anesthetic into the surgical
      wound after abdominal hysterectomy. Patient satisfaction was included among the
      outcomes assessed. MATERIAL AND METHODS: Prospective pilot study in ASA 1-2
      patients randomized to 2 groups: women in the subcutaneous catheter group
      received intravenous analgesics plus a continuous infusion (2 mL/h) of 0.25%
      bupivacaine whereas women in the control group received only the intravenous
      analgesics. The outcome measures were pain intensity assessed on a verbal
      numerical scale at rest and with movement, morphine requirements in the first 48
      hours after surgery, and complications related to the drugs used or the
      technique. RESULTS: Twenty-six patients were enrolled; 10 were randomized to the
      catheter group and 16 to the control group. Statistically significant between
      group differences in pain both at rest and with movement were found while the
      women were in the postoperative recovery unit. Postoperative pain with movement
      was also significantly different at 24 hours (P<.004) and 48 hours (P<.02).
      Similarly, mean (SD) morphine requirements in the recovery unit were
      significantly greater in the control group, at 8 (2.27) mg, compared with 3.20
      (1.79) mg in the catheter group (P<.002). Walking began earlier in the catheter
      group. No differences were found in the incidences of complications. CONCLUSIONS:
      Postoperative pain is effectively relieved by continuous infusion of local
      anesthetic into the surgical wound after abdominal hysterectomy. This technique
      provides good analgesia with less morphine consumption and scarce adverse
      effects. Patient satisfaction and the sense of receiving quality pain management
      are high.

PMID- 19856689
TI  - [Anesthesia for procedures other than neurosurgery in the adult with epilepsy].
AB  - Epilepsy is a common disease affecting between 1% and 2% of the general
      population. The incidence increases with age. Given the complicated etiology and
      pathogenesis of this disease, epileptic patients of all ages may require
      anesthesia. The perioperative care of these patients involves a number of special
      considerations, although the main issues to deal with are pharmacologic. This
      review gives an overview of the etiopathogenesis and pathophysiology of epilepsy
      and describes the general characteristics of antiepileptic drug therapy. The
      anesthetic implications of chronic treatment with antiepileptic agents and the
      interactions between these drugs and common anesthetics are discussed in more
      detail.

PMID- 19856690
TI  - [A proposal for competencies in anethesiology, intensive recovery care, and pain
      therapy: the consensus of university faculty members in Catalonia regarding
      expectations for medical school graduates].

PMID- 19856691
TI  - [Using the CTrach Laryngeal Mask Airway in the awake patient with an expected
      difficult airway].
AB  - The method of choice for managing the expected difficult airway is tracheal
      intubation with an awake patient breathing spontaneously. The CTrach Laryngeal
      Mask Airway (LMA) is a modified version of the Fastrach LMA that incorporates a
      fiberoptic system that provides a view of the glottis during ventilation and
      intubation. We describe 2 cases of intubation in which the CTrach device was used
      in patients breathing spontaneously. In both cases difficult intubation was
      foreseen. The CTrach LMA facilitates management of the airway in these
      circumstances. It is well tolerated and enables a clear view of the airway and
      permits assisted ventilation when necessary.

PMID- 19856692
TI  - [Air embolism during laparoscopic surgery in an infant girl with Cornelia de
      Lange syndrome].
AB  - Cornelia de Lange syndrome involves multiple malformations with particular
      phenotypic features (craniofacial abnormalities such as microcephaly or
      hypertrichosis with synophrys; cutaneous abnormalities such as hirsutism, and
      limb anomalies) and it is associated with a high percentage of mental retardation
      and complications such as digestive tract abnormalities, cardiac defects, and
      endocrine disorders. We report the case of a 2-month-old infant girl who
      underwent a laparoscopic antireflux procedure, with closure of a diaphragmatic
      hernia and a gastric stoma. The medical history included repeated episodes of
      aspiration pneumonia and hypertension. Early in the procedure, 2 episodes of
      sudden desaturation, hypotension, and bradycardia with a probable diagnosis of
      air embolism. The complications resolved with specific treatment. Anesthetic
      management for laparoscopic surgery in these patients is truly complex and must
      be informed by a thorough understanding of the disease and complications that may
      develop.

PMID- 19856693
TI  - [Horner syndrome during epidural analgesia for labor, possibly due to subdural
      spread].

PMID- 19856694
TI  - [Management of a difficult airway due to a large multinodular goiter].

PMID- 19856695
TI  - [Comments on "Sedation with sevoflurane for magnetic resonance imaging in
      pediatrics: retrospective study of 5864 cases"].

PMID- 19856696
TI  - [Perioperative anesthetic management for dermolipectomy and abdominal wall
      reconstruction in a morbidly obese patient with a giant abdominal fat apron].

PMID- 19856697
TI  - [Foreign body in the distal portion of a segmental bronchus].

PMID- 19856698
TI  - [Metal antenna fragment lodged in the tracheobronchial tree].

PMID- 19856699
TI  - Humanizing the homeless: does contact erode stereotypes?
AB  - This paper employs a field experiment to assess whether interpersonal contact
      changes domiciled individuals' attitudes of the homeless. Volunteers for Project
      Homeless Connect-a one-day event that provides social services to the homeless
      were asked to complete a pre- and post-survey. The results provide mixed support
      for the contact hypothesis. After volunteering, respondents were far less likely
      to see homelessness as the result of individual characteristics, such as
      substance abuse or work aversion. However, opinion was remarkably stable when it
      came to policy preferences. The results cast doubt on the conventional wisdom
      that individuals' perceptions of the causes of homelessness track closely with
      their preferences for governmental policy.

PMID- 19856700
TI  - Parental divorce, sibship size, family resources, and children's academic
      performance.
AB  - Using data from 19,839 adolescents from the National Education Longitudinal
      Study, this study investigates whether the effects of parental divorce on
      adolescents' academic test performance vary by sibship size. Analyses show that
      the negative effect of divorce on adolescent performance attenuates as sibship
      size increases. On the other side of the interaction, the inverse relationship
      between sibship size and test performance is weaker in disrupted than in two
      biological-parent families. Trends of such interactions are evident when sibship
      size is examined either as a continuous or a categorical measure. Finally, the
      observed interactions on adolescents' academic performance are completely
      explained by variations in parental financial, human, cultural, and social
      resources. In sum, this study underlines the importance of treating the effect of
      parental divorce as a variable and calls for more research to identify child and
      family features that may change the magnitude of such an effect.

PMID- 19856701
TI  - Religion and intimate partner violence in Chile: macro- and micro-level
      influences.
AB  - The Catholic Church has had a strong influence on the Chilean legal and social
      landscape in ways that have adversely affected victims of intimate partner
      violence; e.g., it succeeded until just five years ago in blocking efforts to
      legalize divorce. At the same time, quantitative studies based on survey data
      from the United States and other countries show a generally favorable influence
      of religion on health and many other domains of life, including intimate partner
      violence. The present study explores the puzzle posed by these seemingly opposing
      macro- and micro-level forces. Results based on data from the 2005 Survey of
      Student Well-Being, a questionnaire on gender-based violence administered to
      students at a large public university in Chile, show that moderate or low levels
      of religiosity are associated with reduced vulnerability to violence, but high
      levels are not. This non-linearity sheds light on the puzzle, because at the
      macro level the religious views shaping Chile's legal and social environment have
      been extreme.

PMID- 19856702
TI  - Normative or economic behavior? Fertility and women's employment in Israel.
AB  - Women's employment and childrearing are competing activities, which exert much
      pressure on their time and energy. Many studies have found that women in paid
      employment, especially in a demanding career, limit their fertility and have few
      children or none. This negative correlation was explained mainly in terms of
      opportunity costs and the incompatibility of women's employment and childrearing.
      This study focuses on the interplay between women's employment and fertility
      decisions in Israel, a socially diverse country, characterized by high levels of
      both fertility and female employment. We argue that in an environment which
      supports and encourages high fertility women's employment activity is less
      consequential for family planning. The study analyzes simultaneously the decision
      to have a third child and the decision to work. The findings show that fertility
      affects negatively women's work activity, but women's employment has no effect on
      their decision to have an additional child. Also, cultural variables affect the
      fertility decision but not economic considerations, while the opposite holds for
      the work decision.

PMID- 19856703
TI  - Blessed assurance: religion, anxiety, and tranquility among US adults.
AB  - A growing body of research investigates the possible relationships between
      religion and mental health. After developing a series of arguments linking
      various aspects of religion with anxiety and tranquility, we test relevant
      hypotheses using data from the 1996 Genera Social Survey. Results show that
      frequency of religious attendance and the belief in an afterlife are inversely
      associated with feelings of anxiety and positively associated with feelings of
      tranquility. However, frequency of prayer has no direct association with either
      outcome. Strong beliefs in the pervasiveness of sin are positively linked with
      anxiety but unrelated to tranquility. Finally, belief in an afterlife and
      frequency of prayer buffer the adverse effects of poor health and financial
      decline on anxiety. Implications of these find ings are discussed along with
      study limitations and promising directions for future research.

PMID- 19856704
TI  - Economic deprivation and racial segregation: comparing Superfund sites in
      Portland, Oregon and Detroit, Michigan.
AB  - The research presented here weighs the ability of two major explanations of
      social inequality-Massey and Denton's racial segregation explanation and Wilson's
      emphasis on economic deprivation (concentrated poverty)-to predict environmental
      inequality. Two sets of logistic regression analyses are used to predict the
      location of Superfund sites in Portland, Oregon and Detroit, Michigan providing a
      conditional understanding of environmental inequality within a larger
      sociological context. The analysis includes a general examination of the two
      theories in all census tracts in both cities and a set of analyses focusing upon
      Black neighborhoods in Detroit. The findings indicate that there is support for
      explanations of environmental inequality that include both racial segregation and
      economic deprivation, but that the more powerful of the two is economic
      deprivation. The results suggest that even though African-American neighborhoods
      disproportionately house Superfund sites, these facilities are more likely to be
      located in Black neighborhoods that are economically deprived.

PMID- 19856705
TI  - Racial diversity, minority concentration, and trust in Canadian urban
      neighborhoods.
AB  - Using a sample of 42,329 respondents nested within 4254 Canadian urban
      neighborhoods, this study demonstrates the conceptual and empirical importance of
      making a distinction between neighborhood racial diversity and minority
      concentration, and examines how each is uniquely associated with trust Our
      analysis shows that at a given level of racial minority concentration, Whites are
      more trusting when their minority neighbors are more evenly distributed across
      racial minority groups. Meanwhile, Whites are less trusting as the neighborhood
      share of racial minorities increases. Overall, the effect of racial minority
      concentration tends to prevail over that of racial diversity.

PMID- 19856706
TI  - Immigration and violence: the offsetting effects of immigrant concentration on
      Latino violence.
AB  - Despite longstanding interest in the effects of immigration on American society,
      there are few studies that examine the relationship between immigration and
      crime. Drawing from social disorganization theory and community resource/social
      capital perspectives, this study examines the effects of Latino immigration on
      Latino violence. Data on violence (i.e., homicide, robbery, and Violent Index)
      and the structural conditions of Latino populations are drawn from the California
      Arrest Data (CAL), New York State Arrest Data (NYSAD), and U.S. Census data for
      approximately 400 census places during the 1999-2001 period. Findings suggest
      that immigrant concentration has no direct effect on Latino homicide or Violent
      Index rates but may reduce Latino robbery. Immigration also appears to have
      multiple, offsetting indirect effects on Latino violence that work through social
      disorganization and community resource measures. These results suggest that (1)
      immigrant concentration does not contribute to Latino violence and may even
      reduce some forms of violence, (2) immigration simultaneously stabilizes and
      destabilizes structural conditions in Latino populations, and (3) it is useful to
      examine both the direct and indirect effects of immigration on crime.

PMID- 19856707
TI  - Immigrant generation, selective acculturation, and alcohol use among Latina/o
      adolescents.
AB  - Do alcohol use and binge drinking among Latina/o adolescents increase in the
      second and third generation? This study explores generational differences in
      alcohol use behaviors for three Latina/o ethnic groups. Using data from the
      National Longitudinal Study of Adolescent Health on 1504 Latina/o adolescents in
      secondary school, we found that the factors associated with alcohol use behaviors
      differed across the Latina/o groups. For Mexican and Cuban adolescents, but not
      Puerto Ricans, immigrant generation was associated with alcohol use. For Mexican,
      but not Cuban adolescents, acculturation mediated the effect of immigrant
      generation on alcohol use behaviors. Although generally social capital and a co
      ethnic presence were protective factors against alcohol use behaviors, we found
      that some forms of social capital were actually risk factors for Cubans and
      Puerto Ricans. Our results provide support for segmented-assimilation theory.

PMID- 19856708
TI  - The effect of climate on migration: United States, 1995-2000.
AB  - This paper examines the effect of climate on migration. We examine whether
      climate is an influential factor in internal migration. We assume that most
      persons tend to avoid exposure to bitter and cold winters, and excessively hot
      and humid summers, preferring climates between these extremes. When engaging in
      migration decision-making, therefore, to the extent possible, considerations
      involving climate are believed to be brought into the calculus. There is a very
      limited demographic literature on the effects of climate on migration. In this
      paper, we undertake an aggregate-based analysis of the effect of climate on
      migration. We examine this relationship among the 50 states of the United States.
      We focus attention on the varying effects of climate on three migration measures
      for the 1995-2000 time period, namely, in-migration, out-migration, and net
      migration. We next evaluate the effect of climate on migration in the context of
      a broad application of human ecology. Here climate, a manifestation of the
      physical environment, is measured with three major independent variables. The
      other ecological predictors pertaining to organization, population, technology,
      and the social environment are used as controls. This enables us to examine the
      effects of climate on migration in the context of competing ecological
      hypotheses.

PMID- 19856709
TI  - Health care reform looks to nursing.

PMID- 19856710
TI  - Animal model of metastatic pheochromocytoma: evaluation by MRI and PET.
AB  - OBJECTIVE: The development of metastatic pheochromocytoma animal model provides a
      unique opportunity to study the physiology of these rare tumors and to evaluate
      experimental treatments. Here, we describe the use of small animal imaging
      techniques to detect, localize and characterize metastatic lesions in nude mice.
      METHODS: Small animal positron emission tomography (PET) imaging and magnetic
      resonance imaging (MRI) were used to detect metastatic lesions in nude mice
      following intravenous injection of mouse pheochromocytoma cells. [18F]-6-fluoro
      dopamine ([18F]-DA) and [18F]-L-6-fluoro-3,4-dihydroxyphenylalanine, which are
      commonly used for localization of pheochromocytoma lesions in clinical practice,
      were selected as radiotracers to monitor metastatic lesions by PET. RESULTS: MRI
      was able to detect liver lesions as small as 0.5mm in diameter. Small animal PET
      imaging using [18F]-DA and [18F]-DOPA detected liver, adrenal gland, and ovarian
      lesions. CONCLUSION: We conclude that MRI is a valuable technique for tumor
      growth monitoring from very early to late stages of tumor progression and that
      animal PET confirmed localization of metastatic pheochromocytoma in liver with
      both radiotracers.

PMID- 19856711
TI  - Adrenal plasma steroid relations in glucocorticoid-naive premenopausal rheumatoid
      arthritis patients during insulin-induced hypoglycemia test compared to matched
      normal control females.
AB  - OBJECTIVE: Clinical and experimental data indicate the involvement of adrenal
      steroids in the complex of rheumatoid arthritis (RA) pathogenesis. A subtle
      adrenocortical hypocompetence has been suggested in a subset of glucocorticoid
      naive premenopausal females with RA. METHODS: The interrelations among adrenal
      steroids: cortisol (CORT), 17alpha-hydroxyprogesterone (17-OHP), androstenedione
      (ASD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS)
      were evaluated in 15 glucocorticoid-naive premenopausal females with RA and in 14
      age- and body mass index- matched healthy females at basal and during insulin
      induced hypoglycemia states. Spearman's correlations were used to analyze
      baseline plasma concentrations as well as areas under response curves of these
      steroids levels as assayed during the basal and/or insulin-induced hypoglycemia
      status. RESULTS: Six among 15 RA patients, but none of 14 controls had combined
      "lower" quartile range of basal cortisol (< 431 nmol/l) and lower DHEAS (< 2.79
      micromol/l) levels, i.e., concentrations within the lowest quartiles of the
      control group (p = 0.017). In all subjects combined, basal correlations were
      significantly positive between ASD and other steroids (CORT, 17OHP, DHEA, DHEAS).
      When patient and control groups were analyzed separately, the positive basal
      correlation between ASD and CORT was significant only in RA patients (p = 0.030).
      In contrast, a positive basal correlation between ASD and DHEA was significant
      only in controls (p = 0.004). When comparing the areas under response curves
      (AUCs), the correlation of ASD and CORT was significantly negative in RA (p =
      0.009), but positive in controls (RA vs control difference in Spearman's
      correlations, p = 0.002). The correlation between AUCs of ASD and DHEA was
      strongly positive in controls (p = 0.006), but not in RA (RA vs. control
      difference p = 0.044). CONCLUSIONS: The results suggest relative hypocompetence
      of adrenocortical function in premenopausal RA females. Different patterns of
      correlations of the adrenal steroids during basal vs. stimulatory testing
      suggested certain alterations in adrenal synthetic pathways or deficiencies in
      the dynamics of steroidogenesis in RA.

PMID- 19856712
TI  - Increased prevalence and coincidence of antinuclear and antithyroid antibodies in
      the population exposed to high levels of polychlorinated pollutants cocktail.
AB  - OBJECTIVES: Because of well known association between the exposure to persistent
      organochlorinated pollutants (POPs) and impaired immune system, it was attempted
      to check possible coincidence of nuclear and thyroperoxidase antibodies with the
      levels of major POPs. METHODS: Antinuclear antibodies. (ANA) were estimated by
      indirect immunofluorescence test using Hep2- cells and thyroperoxidase antibodies
      (TPOab) by electrochemiluminiscent immunoassay in the cohort of 253 adults (82
      males and 171 females) aged 21-75 years, among them 144 (46 males and 98 females)
      from the area polluted (POLL) by polychlorinated biphenyls (PCB) and 109 (36
      males and 73 females) from the area of background pollutrion (BCGR). In the same
      cohort fifteen congeners of PCB and also total DDE (2,2'-bis(4-chlorophenyl)-1,1
      dichloroethylene) and hexachlorobenzene (HCB) were estimated by high resolution
      gas chromatography/mass spectrometry. RESULTS: Prevalence of ANA only was
      significantly higher in POLL than in BCGR in males (p < 0.001) and females (p <
      0.001) and the same was true for the prevalence of TPOab in males (p < 0.05) and
      females (p < 0.01) from POLL. In addition, also the prevalence of coincident
      ANA+TPOab in males (p < 0.001) and females (p < 0.05) was significantly higher in
      POLL. In a total of 253 pooled males and females from both areas and stratified
      in terms of PCB level quintiles. The prevalence of ANA in the 4th and 5th
      quintile of each among three pollutants (PCB, DDE and HCB) was significantly
      higher (p < 0.01 or < 0.001) and showed the parallel increase with the level of
      all pollutants. CONCLUSIONS: Significantly increased prevalence of ANA either
      only or in coincidence with TPOab was found related to increasing level of PCB,
      DDE and HCB.

PMID- 19856713
TI  - The relation between preoperative ultrasonographic thyroid volume analysis and
      thyroidectomy complications.
AB  - OBJECTIVE: To determine the relation between thyroid volume (ThV) and
      thyroidectomy complications using preoperative ultrasound and ellipsoid
      volumetric analysis in Turkish patients. PATIENTS AND METHODS: This prospective
      study included a total of 500 patients (401 females = 80.2% and 99 males = 19.8%)
      who were operated for benign goiter. According to their ThV estimated by
      ultrasound hey were classified in three groups: 1. less than 50 ml (n = 269;
      53.8%), 2. between 50 and 100 ml (n = 151; 30.2%), 3. more than 100 ml (n = 80;
      15.6%). By comparing the association of thyroid volume with peroperative and
      postoperative complications it was evaluated whether the thyroid volume could be
      an effective factor participating in morbidity and mortality of patients.
      RESULTS: Total peroperative complication rate was 2% (n = 10) with trachea injury
      in 2 (0.4%), bleeding in 8 (1.6%) patients. Peroperative complications were
      significantly more frequent in patients with large volume (p = 0.003). Temporary
      hypocalcemia rate in patients with less than 50 ml volume was highly significant
      (p < 0.001). Volume average was low in patients with hypocalcemia as compared to
      patients without hypocalcemia (p < 0.001). Both the temporary and permanent vocal
      cord paralysis (VCP) were significantly more frequent in patients with larger
      volumes (p = 0.002). All four patients with permanent VCP had more than 100 ml
      volume. CONCLUSION: Thyroid volume is an important factor affecting thyroidectomy
      complications. In patients with smaller ThV increased risk of hypocalcemia was
      found, whereas in those with larger ThV increased risk of recurrent nerve damage
      and peroperative bleeding was observed.

PMID- 19856714
TI  - Diagnosis, localization and treatment of pheochromocytoma in MEN 2 syndrome.
AB  - Pheochromocytomas/paragangliomas (PHEOs/PGLs) in patients with MEN 2 are usually
      found in the adrenals after the manifestation of medullary thyroid cancer. These
      PHEOs are commonly bilateral and hormonally active. Tachycardia, diaphoresis and
      cephalalgia are encountered in 40 %-80 % of patients with PHEOs; hypertension is
      very prevalent. Plasma concentrations of free metanephrines (or free
      metanephrines in urine) are best used for the biochemical diagnosis of PHEO/PGL.
      In patients with biochemically-proven PHEOs/PGLs, anatomical imaging with
      computed tomography (CT) and/or magnetic resonance imaging (MRI) should be used.
      False-positive CT/MRI studies can ensue and the specificity of CT/MRI may vary
      from 50%-90%. Functional imaging (implementing nuclear medicine modalities)
      should follow anatomical imaging; modalities with PHEO/PGL-specific ligands are a
      first choice. Among these specific modalities positron emission tomography (PET)
      with [18F]-fluorodopamine ([18F]DA) stands out as the best overall method. If
      PHEO/PGL-specific modalities turn out to be negative functional imaging should
      follow with nonspecific modalities (particularly if recurrent, metastatic or
      malignant disease is suspected). Treatment is surgical, with expanding use of
      laparoscopic approaches. Overall half of the patients with malignant PHEOs remain
      alive for 5 years.

PMID- 19856715
TI  - Molecular studies of DO alleles reveal that JO is more prevalent than HY in
      Brazil, whereas HY is more prevalent in New York.
AB  - Because of the scarcity of anti-Hy and anti-Jo(a), hemagglutination typing for
      the Dombrock blood group system antigens, Hy and Jo(a), is not feasible. The
      molecular bases associated with these antigens have been determined, making it
      possible to distinguish HY and JO from wild-type DO. This provides a tool to
      predict the probable phenotype of patients and to screen for antigen-negative
      donors. PCR-RFLP assays and a microchip assay were used to determine the
      frequency of HY and JO alleles in donors from Brazil and New York. DNA from
      random Brazilian donors, 288 by PCR-RFLP and 599 by the bead array method
      (BeadChip, BioArray Solutions, Warren, NJ), was tested to determine 323G/T
      (HY+/HY-) and 350C>T (JO+/JO-) single-nucleotide polymorphisms. In New York,
      27,226 donors who self-identified as being African American were tested by
      hemagglutination with anti-Gy(a). Nonreactive and weakly reactive samples were
      tested by PCR-RFLP for the same alleles as listed above. In Brazil, 30 (3.4%) of
      the samples were JO/DO and 13 (1.4%) were HY/DO. In New York, of the samples that
      had HY or JO alleles, 14 were homozygous HY/HY 132 were heterozygous HY/DO, 13
      were heterozygous HY/JO, 14 were heterozygous JO/DO, and 3 were homozygous JO/JO.
      These results show that in donors from Brazil, JO (30 alleles) is more than twice
      as prevalent as HY (13 alleles), whereas in donors from New York, HY (173
      alleles) was more than five times more common than JO (33 alleles).

PMID- 19856716
TI  - The O2 allele: questioning the phenotypic definition of an ABO allele.
AB  - There are three main alleles in the ABO blood group system, A, B, and O. The
      former two alleles encode glycosyltransferases resulting in the wild-type A and B
      phenotypes, whereas the latter allele does not encode a functional enzyme owing
      to a frameshift polymorphism in the majority of cases. Thus the group O phenotype
      is the absence of A or B sugars. More than 15 years ago the O2 allele was
      described; this allele did not feature the usual crippling 261delG polymorphism,
      which up to that point was the hallmark of an allele encoding group O, but
      instead had several other nucleotide polymorphisms that reduced or eliminated the
      activity of its resulting protein. The classification of this type of allele as
      encoding group O has been called into question of late as some individuals with
      an O2 allele appear to have a weak A phenotype. Others with the same allele do
      not demonstrate any A antigens on their RBCs but might be involved in reverse
      typing discrepancies. Even within the same pedigree these alleles do not
      necessarily produce a consistent phenotype. This paper will summarize the
      detailed biochemical and population-based evidence both for and against the O2
      allele's ability to create A antigens or the absence of anti-A in plasma.

PMID- 19856717
TI  - Molecular analyses of GYPB in African Brazilians.
AB  - The molecular background of variant forms of GYPB is not well studied in
      Brazilians of African descent. The present study was carried out to determine the
      molecular bases of the S-s- phenotype and the frequency of GYPB*S silent gene for
      the S-s+ phenotype in a blood donor population of African Brazilians. In this
      study, 165 blood samples from African Brazilians (Northeastern Brazil) who
      phenotyped as S-s- (n = 17) and S-s+ (n = 148) by hemagglutination were selected.
      Allele-specific (AS)-PCR and PCR-restriction fragment length polymorphism (RFLP)
      were used to identify the variant forms of GYPB. In 13 of 17 S-s- samples
      (76.5%), both GYPB were deleted. In 137 of the 148 S-s+ samples (92.6%), the AS
      PCR was consistent with the S-s+ phenotype. In 4 of the S-s- samples (23.5%) and
      11 of the S-s+ samples (7.4%), the AS-PCR showed the presence of a GYPB*S allele
      associated with silencing of S. In the 4 donors with the S-s- phenotype, there
      was homozygosity (or hemizygosity) for the GYP(P2) allele (n = 2), homozygosity
      (or hemizygosity) for the GYP(NY) allele (n = 1), and heterozygosity for the
      GYP(P2) and GYP(NY) alleles (n = 1). In the 11 donors with the S-s+ phenotype,
      there was heterozygosity for GYP(P2) allele (n = 8) and heterozygosity for
      GYP(NY) allele (n = 3). This study reports for the first time the molecular
      mechanisms responsible for the S-s- phenotype in a population of African
      Brazilians and provides new information about the frequency and molecular bases
      of the GYPB*S silent gene (7.4%) in this population.

PMID- 19856718
TI  - Rapid, single-subject genotyping to predict red blood cell antigen expression.
AB  - Genotyping is useful to predict the expression of those RBC antigens for which
      antisera are difficult to obtain and to determine the probable phenotype of
      highly transfused patients, and it can be used to test stored DNA when a blood
      sample is not available. This study assessed a sequence-specific primer (SSP)
      based genotyping system for blood group alleles suitable for the rapid testing of
      a small number of samples and assessed the use of stored whole blood. Genomic DNA
      was isolated from fresh and 1- and 2-week-old stored blood from 20 donors with
      known ABO and Rh phenotypes and was used for ABO, RHD, and RHCE genotyping using
      SSPs. The amplicons were analyzed using gel electrophoresis and a novel
      microfluidic on-chip electrophoresis system. Analysis of DNA from fresh and 1-
      and 2-week-old blood by SSP and gel electrophoresis yielded the correct ABO, RHD,
      and RHCE type in all samples, but with DNA from 2-week-old stored blood the
      amplicons were more difficult to visualize. Analysis of the same samples with the
      SSP on-chip electrophoresis assay correctly typed all samples except for one RHCE
      typing discrepancy of a fresh sample and one RHCE typing discrepancy of a 2-week
      old sample. Analysis of amplicons by on-chip electrophoresis required one tenth
      the DNA that gel electrophoresis did and could be completed within 30 minutes
      compared with 2 hours with gel electrophoresis. Amplicons were also more readily
      visualized with on-chip electrophoresis. Fresh and 1- and 2-week-old samples
      could be ABO and RH genotyped with SSP. Analysis using on-chip electrophoresis
      was easier and more rapid than that using gel electrophoresis, but test
      reliability was slightly more variable.

PMID- 19856719
TI  - RHD deletion in a patient with chronic myeloid leukemia.
AB  - Anomalous expression of the Rh antigen, D, has occasionally been observed in
      patients with certain myeloproliferative disorders. Indeed, this phenomenon led
      to the tentative assignment of RH to the short arm of chromosome 1. PCR-based
      analyses were performed on DNA from an 82-year-old D+ Caucasian patient with
      chronic myeloid leukemia after her RBCs became D-. For nearly 7 years, the
      patient's RBCs typed as strongly D+, but in March 2006, they typed weakly D+ and
      in August 2006 typed D- by both direct hemagglutination and the IAT. The D-
      typing persisted until the patient's death in September 2006. To study the
      underlying cause of the change in D type, PCR-based assays were performed on DNA
      extracted from peripheral WBCs from the patient's sample collected in August
      2006. No amplification was obtained using primers designed to amplify RHD exons
      5, 8, or 10, and intron 4. Very weak amplification was obtained using primers
      designed to amplify RHD exons 3, 4, or 7. Two assays that detect the hybrid
      Rhesus box showed deletion of RHD. Amplification of RHCE in the patient's DNA was
      as efficient as that of control samples, and multiplex and PCR-RFLP assays
      predicted her RBCs would be C-E-c+e+. Based on finding a hybrid Rhesus box and
      absence of D-specific exons, we conclude that DNA from the patient's WBCs carries
      a deleted RHD. This explains the molecular mechanism underlying the change from
      D+ to D-.

PMID- 19856720
TI  - From DNA to blood groups.
AB  - A blood group antigen is a protein or carbohydrate on the outer surface of a RBC.
      Portions of DNA are transcribed and translated into proteins. A protein-based
      blood group antigen is the direct product of a gene whereas a carbohydrate-based
      blood group antigen is an indirect product of a gene; the gene product is a
      glycosyltransferase that transfers a carbohydrate moiety to a protein, or to
      another carbohydrate to form a chain of sugars. This report gives a brief
      description of a gene, its processing from DNA through RNA to an amino acid
      sequence, and how changes in nucleotides give rise to blood group antigens.

PMID- 19856721
TI  - Principles of PCR-based assays.
AB  - DNA-based assays are powerful tools to predict the blood group of an individual
      and are rapidly gaining in popularity. DNA, which can be extracted from various
      sources using commercial kits, is amplified by PCR to obtain a sufficient amount
      of the target of interest for analysis. There are different types of PCR assays:
      standard single PCR (followed by RFLP or sequencing), allele-specific PCR,
      multiplex PCR, and real-time PCR. Microarray platforms are a newer application of
      molecular testing, popular because they analyze multiple nucleotides in a single
      assay and have a high-throughput potential. This review briefly describes the
      principles of PCR-based assays that are commonly used in transfusion medicine.

PMID- 19856722
TI  - Value of DNA-based assays for donor screening and regulatory issues.
AB  - Hemagglutination, the gold standard method to detect the presence or absence of
      blood group antigens on RBCs, has served the transfusion community well for
      decades. It is simple, and, when done correctly, it has a specificity and
      sensitivity that is appropriate for most testing in the vast majority of patients
      requiring blood transfusion. The limitations of hemagglutination for screening
      donor blood include that both testing and data entry are labor-intensive, that
      the required antibody is not always commercially available, and that it may be
      limited in volume, weakly reactive, or costly. These scenarios can make it
      difficult to screen for large numbers of antigen-negative blood donors. The
      knowledge of the molecular bases of blood group antigens makes it possible to
      screen donors to predict their antigen status. High-throughput platforms provide
      a means to test relatively large numbers of donors, thereby opening the door to
      change the way antigen-negative blood is provided to patients. This review
      discusses testing for blood group antigens by hemagglutination and bead chip
      technology. It also reviews regulatory issues, including validation and training,
      and suggests an algorithm for screening and confirming blood types of donors.

PMID- 19856723
TI  - DNA-based assays for patient testing: their application, interpretation, and
      correlation of results.
AB  - DNA analysis for the prediction of RBC phenotype has broad implication in
      transfusion medicine. Hemagglutination testing, long the gold standard for
      immunohematology testing, has significant limitations. DNA analysis affords a
      useful addition to the arsenal of methods used to resolve complex serologic
      investigations. This report discusses the interpretation of results obtained by
      DNA analyses and their correlation with serologic results. Some current
      applications to resolve serologic problems encountered in patient testing are
      reviewed and case studies are presented to demonstrate the power of combining DNA
      analysis with hemagglutination.

PMID- 19856724
TI  - The potential of blood group genotyping for transfusion medicine practice.
AB  - Molecular diagnostics is the fastest growing area of clinical laboratory
      medicine. The ability to rapidly amplify genes of bacterial, viral, or human
      origin, and the development of DNA array platforms, are driving a technology
      revolution in the clinical laboratory. A DNA-based testing approach is
      particularly applicable to blood bank and transfusion medicine for rapid, cost
      effective antigen typing. Experience with DNA-based methods during the past
      decade has shown that these assays are reproducible and highly correlated with
      the RBC phenotype. The recent availability of automated, high-throughput, DNA
      array platforms now moves testing from the reference laboratory setting into
      hospital and donor testing centers. This approach has the potential to
      revolutionize the process of locating antigen-negative donor units by testing for
      all clinically significant blood group antigens in a single assay. When partnered
      with the same extended typing of the patient, electronic selection of units
      antigen-matched at multiple blood group loci is then possible. This paper
      discusses the potential of this approach to improve transfusion therapy by
      reducing or eliminating alloantibody production in specific patient populations.
      These include patients facing long-term transfusion therapy and at high risk for
      sensitization; patients with warm autoantibodies when compatibility cannot be
      demonstrated by standard methods; and women for whom the production of atypical
      antibodies carries a risk for hemolytic disease of the fetus and newborn, or at
      the very least, monitoring for an at-risk pregnancy.

PMID- 19856725
TI  - D+ platelet transfusions in D- patients: cause for concern?
AB  - Patients whose RBCs are D- may produce anti-D if they are exposed to D on donor
      RBCs. Except in emergency situations, patients whose RBCs lack D are transfused
      with only D- RBCs. Platelets carry no Rh antigens, but platelet units may be
      contaminated by RBCs that could carry D when these units are collected from D+
      donors. The purpose of this study was to determine whether our policy of allowing
      D+ platelets to be transfused to patients whose RBCs type as D-, without the use
      of prophylactic Rh immunoglobulin (RhIG), results in D alloimmunization. The
      transfusion records of all patients who received platelet transfusions from
      December 2004 to March 2007 were reviewed. Transfusion recipients were evaluated
      with pretransfusion ABO and D typings, and an antibody screen. Recipients were
      reevaluated in the same manner before subsequent transfusions. Transfusion
      records of 114 D- patients were analyzed. Overall, 104 patients received D+
      platelets; 67 had repeat antibody screening after transfusion. No patients were
      shown to make anti-D after platelet transfusion. There was no evidence of D
      alloimmunization as a result of transfusion of D+ platelets in any D- patient
      during this study. The data do not support the practice of restricting D-
      patients to receiving only D- apheresis platelets, even among patients with
      chronic transfusion requirements. Prophylactic use of RhIG for D+ apheresis
      platelet transfusions in D- patients also appears to be unnecessary.

PMID- 19856726
TI  - Autoantibody formation after alloimmunization inducing bystander immune
      hemolysis.
AB  - The development of RBC autoantibodies resulting from or associated with
      allogeneic blood transfusions is not an easily determined complication of RBC
      transfusions. This report discusses one patient who developed RBC autoantibodies
      in association with an allogeneic blood transfusion and alloimmunization leading
      to a temporary bystander immune hemolysis. A 72-year-old woman was hospitalized
      as a result of severe anemia and received two units of ABO- and D-compatible
      RBCs. She had a history of two pregnancies 40 years before, but no history of RBC
      transfusion, and her antibody screen was negative. On the tenth day after
      transfusion her hemoglobin dropped, and alloanti-c was identified in her serum
      and eluate. At this time she received another two units of compatible blood
      according to her phenotype (group O, R1R1, K:-1). After 48 hours, she developed
      joint pain, pyrexia, and hemoglobinuria, and her Hb dropped from 9.2 g/dL to 5.3
      g/ dL. The direct antiglobulin test was positive, an IgG autoantibody was present
      in the eluate, and the antibody investigation revealed the presence of anti-Jk(b)
      in addition to the previously identified alloanti-c. Her genotype was determined,
      and, based on the findings, two additional units were selected, found to be
      compatible, and transfused without incident. Transfusions were discontinued, and
      she was treated with IVIG and corticosteroids. Her Hb increased to 9.7 g/dL, and
      the patient made an uneventful recovery. It was concluded that transfusion of
      incompatible RBCs induced the formation of an autoantibody in this patient,
      resulting in lysis of bystander RBCs. The need for additional blood transfusion
      was successfully avoided by treatment with IVIG, steroid therapy, and rituximab.

PMID- 19856727
TI  - Transfusion of rare cryopreserved red blood cell units stored at -80 degrees C:
      the French experience.
AB  - The technology allowing freezing of RBC units has been available for many
      decades. The high-glycerol method for RBC storage at -8 degrees C is
      predominantly used. Several studies have shown satisfactory results regarding the
      in vitro viability and function of cryopreserved RBCs. RBC freezing is nowadays
      mostly encountered in rare blood programs and military deployments. Preservation
      time of frozen RBCs appears to be virtually indefinite, but most countries apply
      a 10-year outdate. There is no mandatory time restriction in France. The National
      Rare Blood Bank currently includes 962 (17.5%) RBC units aged to years or more
      and 153 (2.8%) aged 20 years or more. Since 1994, 1957 RBC units have been thawed
      and transfused, among which 118 were aged 10 years or more and 8 were aged 20
      years or more. Discarding RBC units older than to years may be highly sensitive
      for very rare blood groups, e.g., U-, of which approximately 30 percent of the
      cryopreserved units are aged to years or more. However, the lack of nucleic acid
      testing for HIV and HCV may be problematic for old RBC units drawn from donors
      who were not subsequently tested for these markers, which is now mandatory in
      most countries. Regarding the 118 transfused RBC units older than 10 years, no
      evidence of hemolysis of thawed RBCs and no transfusion reaction, clinical or
      biologic hemolysis, or transfusion ineffectiveness was reported, either by any of
      the parties involved in the transfusion supply of rare RBC units or through the
      French hemovigilance program, which requires a mandatory report of any
      transfusion reaction. It has recently been suggested to extend the 10-year
      restriction in some countries. Considering our experience and observational data,
      we may consider it safe and efficient to transfuse rare frozen RBC units older
      than 10 years. An international consensus for RBC cryopreservation time should
      ideally be established.

PMID- 19856728
TI  - The polymorphism nt 76 in exon 2 of SC is more frequent in whites than in blacks.
AB  - The Scianna blood group system comprises seven antigens encoded by alternative
      forms of SC. The SC gene also has two polymorphisms in the leader sequence, at
      nucleotides 54 (C/T, silent) and 76 (C/T, 26His/Tyr) in exon 2, which are not
      involved in expression of blood group antigens. The nucleotide change at position
      76 has an NlaIII restriction enzyme site; thus, DNA samples from 100 Caucasians
      and 100 African Americans were analyzed for the SC nucleotide 76 change. DNA from
      Caucasian and African American donors was tested by polymerase chain reaction
      (PCR)-restriction fragment length polymorphism (RFLP) using the restriction
      enzyme NlaIII. In selected samples, sequencing of exon 2 was performed. PCR-RFLP
      results for samples from 100 donors (mostly Caucasian) and 100 African American
      donors (400 alleles) showed the nucleotide 76T variant had a prevalence of 25
      percent in Whites and 5 percent in African Americans. In 11 samples (2 C/C, 3
      C/T, and 6 T/T) sequencing of exon 2 confirmed the presence of the expected
      nucleotides at position 76. The allele frequency in Caucasians was 0.75 for nt76C
      and 0.25 for nt76T. In African Americans, the frequencies were, respectively,
      0.95 and 0.05.

PMID- 19856729
TI  - Nonhemolytic passenger lymphocyte syndrome: donor-derived anti-M in an M+
      recipient of a multiorgan transplant.
AB  - Passenger lymphocyte syndrome (PLS) is a well-recognized complication that may
      follow a hematopoietic progenitor cell or solid-organ transplant. Typically, the
      syndrome presents as acute hemolysis of the recipient's RBCs, which have become
      serologically incompatible with blood group antibodies formed by passively
      transfused donor-origin B lymphocytes. Most cases involve anti-A or anti-B.
      However, there are cases involving non-ABO serologic incompatibility, as well as
      cases in which the serologic incompatibility was not associated with clinical
      evidence of hemolysis. This report describes a case of passenger lymphocyte
      syndrome in an M+ recipient who developed anti-M after receiving a multiorgan
      transplant from an M- cadaver donor. Although the temporal events and serologic
      findings were consistent with a diagnosis of PLS, there was no evidence of in
      vivo hemolysis associated with the identification of a newly formed anti-M. This
      report includes a literature review of other case reports of PLS associated with
      non-ABO antibodies in solid-organ and hematopoietic progenitor cell transplant
      recipients.

PMID- 19856730
TI  - Development and validation of a fluorescent microsphere immunoassay for anti-IgA.
AB  - Anti-IgA may cause anaphylactic transfusion reactions in IgA-deficient
      individuals. Testing for IgG anti-IgA is useful to identify persons at risk. This
      report describes an immunoassay for anti-IgA that uses polyclonal IgA coupled to
      fluorescent microspheres as an immunosorbent. Anti-IgA is detected by
      phycoerythrin-labeled anti-IgG. The assay is calibrated in arbitrary units by use
      of a serum that contains anti-IgA. Dose-response studies with sera that contain
      anti-IgA showed positive responses at dilutions up to 32-fold greater than the
      dilution used to test patients' samples. Inhibition studies with purified IgA and
      IgA-deficient serum showed no inhibition with IgA-deficient serum and complete
      inhibition with soluble IgA. Clinical tests performed in more than 90 assays had
      a CV of 13.6 percent for measurements of an internal positive control. The
      fluorescent immunoassay method is rapid, reproducible, and sensitive to low
      concentrations of IgG anti-IgA.

PMID- 19856731
TI  - Factor structure of the Adolescent Clinical Sexual Behavior Inventory.
AB  - The primary goal of this study was to determine if the Adolescent Clinical Sexual
      Behavior Inventory-Self-Report conformed to the five-factor scale format that was
      initially used with a clinical sample that included adolescents referred for
      sexual abuse evaluations. Participants were 141 teenagers, ages 12-19 (M = 15.11,
      SD = 1.4), and their primary caregivers. None of the participants were referred
      for sexual abuse evaluations. Principal components analyses found a different
      though similar set of factors. This sample yielded three factors that were
      similar to the original five factors identified by Friedrich, Lysne, Sim, and
      Shamos (2004). That is, the measure was found to reliably assess adolescents'
      sexual knowledge, risky sexual behaviors, and concerns related to appearance.

PMID- 19856732
TI  - The relationship between childhood sexual abuse and sexual dysfunction in
      Jamaican adults.
AB  - This study examined the associations between early traumatic sexualization and
      later sexual dysfunction in a sample of 100 Jamaican adults while identifying the
      linkages between age, frequency of abuse, and gender on sexual functioning.
      Participants were selected via purposive and convenience sampling and divided
      equally into comparison and experimental groups based on sociodemographic
      characteristics. Results indicated that childhood sexual abuse is a likely factor
      in the development of sexual dysfunction in Jamaican adults, especially in the
      domains of Orgasm and Sexual Drive and Relationship. Gender, frequency, and age
      of abuse are also seen to impact specific areas of an individual's sexual
      functioning. Results are discussed in light of previous research for their
      implications in order to better understand sexuality in the Jamaican context.

PMID- 19856733
TI  - Legal and social service responses to child sexual abuse: a primer and discussion
      of relevant research.
AB  - This paper provides a broad overview of legal and social service responses to
      child sexual abuse, the overarching legal framework provided by federal
      legislation, and funding mandates and the unique and shared investigative
      concerns of law enforcement and child protective service entities. Relevant
      psychological research is highlighted throughout, including research on
      investigator training, forensic interviewing techniques, children's
      suggestibility, jurors' perceptions of child witnesses, and courtroom
      accommodations for child witnesses.

PMID- 19856734
TI  - Public attitudes toward sexual offenders and sex offender registration.
AB  - This study explores the relationship between fear of various types of sexual
      offenders and a belief that those sexual offenders should be subject to sex
      offender registration. We hypothesized that those who offend against children
      would elicit the most fear; consequently, the most feared offenders would be
      rated as most requiring registration. As part of a telephone survey, 733
      participants answered questions about fear of sex offenders and agreement with
      requirements about registration for offenders convicted of incest, statutory
      rape, marital rape, pedophilia, date rape, and an offense committed more than 10
      years prior. Results indicated that all types of sexual offenders elicited some
      fear from respondents, and fear was related to support of registration
      requirements.

PMID- 19856735
TI  - Advantages of group therapy for adolescent participants in the same gang rape.
AB  - This paper deals with the issue of including in the same therapeutic group in a
      prison setting two (or more) young people who participated in the same gang rape.
      We provide a background for group therapy with adolescent sex offenders and point
      out the characteristics of group rape. In addition, we describe the uniqueness of
      working in a prison as opposed to working in the community or other settings
      outside the home. Characteristics of adolescent sex offenders and the group
      process provide a rationale against the inclusion in the same therapeutic group
      of two youths who committed a rape together. However, our observations during
      eight years of clinical experience and research in the prison clarify why it can
      and should be done.

PMID- 19856736
TI  - Child sexual abusers' views on treatment: a study of convicted and imprisoned
      adult male offenders.
AB  - In spite of an increasing focus on the assessment and treatment of sexual
      offenders over the past two decades, much debate persists as to the effectiveness
      of treatment in reducing recidivism. Given the dearth of research on offenders'
      perspectives in this area and the potential for offenders' views to inform the
      development of effective treatment, we consider the views of 35 adult male child
      sexual abusers on the prison treatment program. Focusing on a number of key
      themes, namely victim empathy, strategies for desistence, group or individual
      treatment, motivation, and postprogram support. In doing so, the extent to which
      this work furthers knowledge in this area and future research directions was
      considered.

PMID- 19856737
TI  - Sibling family practices: guidelines for healthy boundaries.
AB  - A questionnaire was given to 500 mental health and child welfare professionals
      asking for maximum acceptable ages for siblings to engage jointly in certain
      family practices related to hygiene, affection, and privacy. A large proportion
      of respondents felt it was never acceptable for siblings to take showers together
      (40%), kiss on the mouth (37%), or toilet together (32%). Some significant
      differences occurred based on the gender of the older sibling within sets of same
      gender or mixed gender pairs, with older brothers being acceptable up to lower
      ages than older sisters. The effects of child abuse, age, race, and the amount of
      education on the respondents' answers are investigated. The limitations of the
      age guidelines are discussed.

PMID- 19856738
TI  - Cultural dimension of male sexual behavior and HIV risk in South Asia with
      special emphasis on India: a commentary.

PMID- 19856740
TI  - Multiple risks among male and transgender sex workers in Pakistan.
AB  - Using data from a qualitative study and a subsequent quantitative survey among
      918 male and transgender sex workers (MTSW), we explore the context of multiple
      risks they face. We show that over one-fifth of MTSW have sex with IDU clients.
      Combined with high levels of risk behavior and very low levels of risk reduction
      and knowledge, the extent of sexual networking with men who inject drugs
      contributes further to the sex workers' health risks. Our findings suggest that
      isolated interventions with single-risk groups are unlikely to be sufficient to
      control the spread of the epidemic in Pakistan. We highlight the need for
      integrated approaches to risk reduction programs among MTSW and IDUs.

PMID- 19856739
TI  - Men who have sex with men in India: a systematic review of the literature.
AB  - This study systematically reviews the existing literature on sexually transmitted
      infections (STIs) including human immunodeficiency virus (HIV) infection in the
      men who have sex with men (MSM) in India. After a comprehensive literature search
      of Medline (1950-June 2008), Embase (1980-June 2008), and the Cochrane Library
      (1950-June 2008), 12 published studies met the inclusion criteria. The link
      between sexual identity and sexual behavior is a complex phenomenon strongly
      embedded in a very specific context in India. MSM in India are an important risk
      group for acquiring STIs/HIV and effective culturally sensitive prevention
      programs should be designed for them. The combined estimate of HIV prevalence in
      the MSM population in India calculated from 5 included studies was 16.5% (95%
      confidence intervals: 11% to 22%). The review also identifies the lacunae in
      existing literature and provides future directions for research in the MSM
      community in India.

PMID- 19856741
TI  - Determinants of sexual risk behavior among men who have sex with men accessing
      public sex environments in Chennai, India.
AB  - We conducted structured interviews with 200 men who have sex with men (MSM)
      recruited using time-space sampling from public sex environments (PSEs) in
      Chennai, India. Predictors of sexual risk behavior were assessed with chi2 tests
      and multiple logistic regression. One-third reported unprotected receptive anal
      sex (URAS) last time and 36% inconsistent condom use in the past month. URAS was
      associated with younger age, less than high school education, low income, and low
      HIV transmission knowledge (adjusted odds ratio [AOR] = 2.1, 2.5, 3.7 and 2.5,
      respectively). Inconsistent condom use was associated with less than high school
      education (AOR = 3.2) and low HIV transmission knowledge (AOR = 3.5). Multilevel
      HIV prevention strategies tailored for low socioeconomic kothis and other MSM in
      PSEs in Chennai should include peer interventions to increase knowledge of HIV
      transmission risks and sexually transmitted infections (STIs), and structural
      interventions to expand economic and educational opportunities, and accessible
      STI testing and treatment.

PMID- 19856742
TI  - Exploring context and dynamics of homosexual experiences among rural youth in
      India.
AB  - There is a lack of community-based studies that have examined level and context
      of homosexual activity in India among male youth. As part of a larger study on
      sexual behavior and gender attitudes of rural youth in Northern India, this study
      identified a subgroup of young men who reported homosexual experiences, even
      though they did not identify themselves as homosexual. This article attempts to
      examine the levels and range of sexual practices and attitudes of the
      homosexually active male youth by comparing them with their peers who reported
      heterosexual experiences. Study findings indicate that about one-fifth of
      sexually active male youth reported homosexual experiences. These young men begin
      their sexual careers early; engage with a higher number of sexual partners, both
      male and female; and are more likely to report inconsistent condom use, as
      compared to their heterosexually active peers. With high levels of partner mixing
      and inconsistent condom, use it appears that, for this subgroup of young men with
      high risk behaviors, homosexual experiences are only one part of their sexual
      lives and not the main factor that would contribute to their HIV vulnerability.
      Interventions need to be mindful of these issues, rather than rushing into
      labelling youth as homosexual or heterosexual for programmatic purposes. At the
      same time, as high-risk behaviors are largely unexplored among a general
      population of rural male youth, there is need for more in-depth ethnographic and
      culturally specific sexuality research to explore if there is a subculture that
      may promote sexual practices including same-sex activities that influences HIV
      vulnerability.

PMID- 19856743
TI  - Sexually transmitted infections treatment and care available to high risk
      populations in Pakistan.
AB  - Limited literature exists on the quality and availability of treatment and care
      of sexually transmitted infections (STIs) in Pakistan. This article aims to
      document existing services for the care and treatment of STIs available in
      Pakistan's public and private sectors to high risk groups (HRG), particularly the
      transgendered population. We conducted a cross-sectional survey to document STI
      services in Lahore, Karachi, Rawalpindi, Peshawar, and Quetta. Seventy-three
      interviews were administered with health service providers at the 3 largest
      public sector hospitals in each city, as well as with general physicians and
      traditional healers in the private sector. Twenty-five nongovernmental
      organizations (NGO) providing STI services were also interviewed. Fewer than 45%
      of private and public sector general practitioners had been trained in STI
      treatment after the completion of their medical curriculum, and none of the
      traditional healers had received any formal training or information on STIs. The
      World Health Organization (WHO) syndromic management guidelines were followed for
      STI management by 29% of public and private sector doctors and 5% of traditional
      healers. STI drugs were available at no cost at 44% of NGOs and at some public
      sector hospitals. Our findings show that although providers do treat HRGs for
      STIs, there are significant limitations in their ability to provide these
      services. These deterrents include, but are not limited to, a lack of STI
      training of service providers, privacy and adherence to recommended WHO syndromic
      management guidelines, and costly diagnostic and consultation fees.

PMID- 19856744
TI  - Sexual identity and its contribution to MSM risk behavior in Bangaluru
      (Bangalore), India: the results of a two-stage cluster sampling survey.
AB  - In India, there are categories of MSM (hijras, kothis, double-deckers, panthis
      and bisexuals), which are generally associated with different HIV-risk behaviors.
      Our objective was to quantify differences across MSM identities (n = 357) and
      assess the extent they conform to typecasts that prevail in policy-orientated
      discourse. More feminine kothis (26%) and hijras (13%) mostly reported receptive
      sex, and masculine panthis (15%) and bisexuals (23%) insertive anal sex. However,
      behavior did not always conform to expectation, with 25% and 16% of the sample
      reporting both insertive and receptive anal intercourse with known and unknown
      noncommercial partners, respectively (p < 0.000). Although behavior often
      complied with stereotyped role and identity, male-with-male sexual practices were
      fluid. Reification of these categories in an intervention context may hinder our
      understanding of the differential HIV risk among MSM.

PMID- 19856745
TI  - Not to stigmatize but to humanize sexual lives of the transgender (hijra) in
      Bangladesh: condom chat in the AIDS era.
AB  - Despite condom interventions since year 2000 with the transgender (hijra)
      population, condom use remains low. Consequently, hijra suffer from higher rates
      of active syphilis, putting them under threat of HIV transmission. In an
      ethnographic study, 50 in-depth interviews with diverse groups of hijra along
      with 20 key-informants interviews with various stakeholders, and 13 focus group
      discussions (FGDs) were conducted with comprehensive field observations. Findings
      indicate that most hijra understand the importance of condoms, but none use
      condoms consistently. Complex underlying reasons positioned beyond the
      individual's cognitive domain include: low self-confidence; economic hardships
      for mere survival; multiple transient partners; sexual desire, preferences, and
      eroticisms concerning anal sex; stigma associated with purchasing condoms; poor
      quality and interrupted supply of condoms and lubricants; limitation of fear
      producing messages in favor of condoms; inadequate professional skills and
      motivational impetus of the outreach staff for condom promotion, and incompetent
      management with inadequate understanding about the dynamics of condom use.
      Imposing condoms by disregarding socio-cultural and socio-economic scripts of
      sexual relationships and eroticism of hijra-sexuality have challenged the
      effectiveness of current condom interventions. Interventions should not mechanize
      the process, rather they may humanize and eroticize sexual lives of the hijra. A
      paradigm shift is required where condoms enhance the dignity and quality of
      sexual lives of the hijra beyond the framework of disgrace, disease, and death.

PMID- 19856746
TI  - ['Mercenary wet-nurses': the discourse of medical doctors and portraits of the
      wet-nurses--Brazil in the second half of the 19th century].
AB  - The article explores the theme of wet-nurses using photographs and theses of
      medical doctors during the second half of the 19th century. The doctors at that
      time condemned the indiscriminate use of wet-nurses and tried to encourage
      construction of the 'new mother' image, one who ought to breast feed her own
      children. They approached the complexity of the feeding subject (by mother, wet
      nurse, animal or object) at that time and the problems arising from it for the
      parties involved: the white baby, the black baby, the wet-nurse, the mother of
      the white baby, the seignorial family involved and medical doctors. Photos are
      highlighted of wet-nurses with children in an attitude that was intended to be
      'positive' to demonstrate harmony and affection and, apparently, contradicting
      the debates regarding them.

PMID- 19856747
TI  - [The magic universe of cures: the role of magic practices and witchcraft in the
      universe of 17th century Mato Grosso].
AB  - The article analyzes the role of healing agents played by practitioners of magic
      and witchcraft in Mato Grosso society during the 17th century. It observes that
      magic and witchcraft were developed as competitors, alternatives or associated
      with other forms of healing (official and lay). It points out how such roles
      contributed to the process of subjugating its practitioners, especially Africans,
      Indians and their descendents, and were appropriated as an opportunity for
      survival in the colonial slave society. The pastoral visit made by Bruno Pinna in
      1785 to Cuiaba and nearby areas served as the principal source of knowledge
      regarding the practices and practitioners of magic and witchcraft.

PMID- 19856748
TI  - [Corporate and technological changes in Sao Paulo medicine in 1930].
AB  - Through the historical study of the corporate and technological changes
      experienced by doctors in Sao Paulo in the 1930s, we intend to identify how
      changes in the fields of equipment and knowledge came from the emergence of
      specialties, which led to corporate changes and rearrangements in the face of the
      dilemmas introduced by the Getulio Vargas government and its policy of
      centralizing power. Connections are pointed out of a symbolic and representative
      order, backed by doctors considered 'old-school' and those that represented the
      'new' times in medicine, evidencing the clashes between these currents vis-a-vis
      the specialization movement and particular landmarks in the history of Sao Paulo.

PMID- 19856749
TI  - [Revisiting establishments of the etiology of Turner syndrome].
AB  - Based on an interview with Jose Carlos Cabral de Almeida, who took part in the
      investigative process, the article explores the research that culminated in the
      establishment of the genetic etiology of Turner syndrome. Cabral de Almeida also
      discusses other work that he sees as landmarks in the birth of cytogenetics and
      offers his current view of the development of clinicalgenetics and the important
      role played by cytogenetics, which affords more precise means of diagnosis,
      prognosis, and control ofgenetic disorders. In its conclusion, the article points
      to pioneer work that continues to impact medical genetics, especially the study
      of human chromosomes, still fundamental to the success of linking human genetics
      and disease processes.

PMID- 19856750
TI  - [The design and promotion of health in the Fiocruz research laboratories].
AB  - The article discusses the relationship between the objects and the physical
      environments devoted to research and health promotion. It analyzes the physical
      environment of the Instituto Oswaldo Cruz (IOC/Fiocruz) research laboratories in
      light of such health promotion principles as expanding the concept of health,
      participation by the players in the decision making process regarding health
      areas and the involvement of different disciplines in the planning of these
      environments. It finds a close relationship between design, architecture and
      health promotion throughout the history of Fiocruz and presents interviews
      obtained in the workshop denominated Space, Creation and Happiness, an instrument
      for sensitization, participation and listening utilized by users of the
      laboratory environments, developed and perfected in the IOC/Fiocruz.

PMID- 19856751
TI  - [The socio-cultural bases of alternative therapeutic practices].
AB  - The emergence and development of alternative therapies comprised part of the
      counter-cultural movement initiated in the 1960s. In the health field of the
      western world, the social transformations that occurred at that time inaugurated
      a period in which diverse health cultures coexisted. In this work we elaborate
      the socio-anthropological interpretations of cultural, political and socio
      economic factors that influenced these transformations. First, we identify the
      macrocultural factors that would influence the transformations in the health
      field. Next, within this field we analyze the conflicts and disruptions that
      contributed to the search for new therapeutic practices. We use text analysis as
      the principal methodology, starting from the presupposition that the integrative
      approach of alternative therapies expresses an aspect of the transformation in
      the cultural values contemporaneous societies.

PMID- 19856752
TI  - [The Hospital-Colonia Rovisco Pais: the last Portuguese leprosarium and the
      contingent universes of experience and memory].
AB  - The Hospital-Colonia Rovisco Pais was inaugurated in Portugal in the 1940s for
      the treatment, study and prophylaxis of leprosy based on the compulsive
      internment model, whose configuration reflects the total institution concept
      proposed by Goffman. It concerns an important hygiene project of the Estado Novo.
      Its educative paradigm combined elements inspired in European social medicine and
      the ideology of the paternalistic Portuguese dictatorial regime. The Hospital
      Colony here will be thought of as a disciplinary dispositive, developing
      considerations regarding the confrontation between disciplinary power and
      experience. Memory emerges as a contingent instrument to access the practices and
      interstitial meanings woven into the Hospital Colony's daily life, seeking to
      find out about the experience of its former patients as political subjects.

PMID- 19856753
TI  - [Hansen's disease in Maranhao in the 1930s: on the way to Colonia do Bonfim].
AB  - Some aspects of Hansen's disease and the health policy for those having it in
      Maranhao in the 1930s are pointed out. The resolution of the disease in that
      state followed the precept imposed by the centralizing national health policies
      developed in the Vargas period: greater sanitary vigilance of those having the
      disease and the construction of a compulsory isolation colony for the
      contagiously ill largely characterized the decade regarding the prophylaxis of
      what was then called leprosy. The discourses of Achilles Lisboa, the doctor who
      best expressed this period, are highlighted here, since they contributed to
      aggressively mold the public policies of exclusion directed to those having
      Hansen's disease in Maranhao.

PMID- 19856754
TI  - [The compulsory isolation of Hansen's disease patients: memories of the elderly].
AB  - From 1924 to 1962, Brazil used compulsory internment of Hansen's disease patients
      as one of the ways of controlling the disease in the community. After this policy
      ended, many patients continued to live in these units. The former Asilo
      Pirapitingui, now the Hospital Dr. Francisco Ribeiro Arantes, is the only old
      style asylum for the socially determined internment of those suffering from
      Hansen's disease. Through recorded and transcribed interviews of eight of those
      remaining, we sought to learn their history and the meaning of this isolation in
      their lives. The thematic analysis of the discourse enabled identification of the
      following analysis categories: Hansen's disease; internment day-to-day life; the
      institution; current health conditions; and staying in the institution after the
      end of compulsory internment.

PMID- 19856755
TI  - [The religious imaginary of Hansen's disease patients: a comparative study of
      former inmates of the asylums of Sao Paulo and current Hansen's disease
      patients].
AB  - The article analyzes the religiosity of Hansen's disease patients who lived
      during two distinct treatment periods of the sick: that of internment in asylums
      and the current practice. Ten semi-structured interviews focused on health,
      religion and Hansen's disease, broaching the ways the two groups faced religion.
      In the former inmate group, the presence of institutionalized religion was noted,
      which served the purposes of vigilance and isolationist therapeutics. Present day
      Hansen's disease patients still feel the stigmatic weight of'leprosy" in certain
      situations. Five questionnaires were also given to DHDS health professionals, who
      presented their considerations concerning the patient's religion and the
      treatment.

PMID- 19856757
TI  - Loud and painfully clear.

PMID- 19856758
TI  - Leading with receding resources.

PMID- 19856756
TI  - [Hortensia de Hollanda: the art of health education to prevent and control
      epidemics in Brazil].
AB  - The article presents the transcription of a class given by Brazilian educator
      Hortensia Hurpia de Hollanda entitled: "Educacao sanitaria na profilaxia das
      endemias rurais" [Sanitary education in the prophylaxis of rural epidemics], in a
      refresher course on rural epidemics and included in the Anais da Faculdade
      Fluminense de Medicina in December 1956. The annotated publication of the
      manuscript seeks to prove the pioneering efforts of Hollanda, whose work has been
      seldom investigated, considering the dimension of her role in the area of health
      education in Brazil. Sensitivity to social problems, the importance of the
      population's participation and an experimental attitude are some of the aspects
      presented in the educator's text, revealing an advanced theoretical grounding for
      her times and an original and pioneering practice that remains to this day as an
      ideal to be achieved.

PMID- 19856759
TI  - Sponge blob.

PMID- 19856760
TI  - A picture is worth a thousand words.

PMID- 19856761
TI  - Virtualization = 'elegant' data security. Interview by Jerry Laws.

PMID- 19856762
TI  - Q&A: Steel toe, and much more.

PMID- 19856763
TI  - Are they up to the challenge?

PMID- 19856764
TI  - Cutting noise down to size.

PMID- 19856765
TI  - The role of driver motivation.

PMID- 19856766
TI  - Event draws top names.

PMID- 19856767
TI  - Sustaining acceptable indoor environmental quality.

PMID- 19856768
TI  - Understanding risk control.

PMID- 19856769
TI  - Great expectations.

PMID- 19856770
TI  - Action tracking and EH&S compliance.

PMID- 19856771
TI  - Expect more from your SaaS vendor.

PMID- 19856772
TI  - Partner woes. How to handle working with a slug.

PMID- 19856773
TI  - OK, but how? Part 1: mastering one of the mystery techniques in EMS.

PMID- 19856774
TI  - 'Not like herself at all'. A woman's sudden unusual behavior may have dire
      origins.

PMID- 19856775
TI  - System solutions. An interview with David Williams on handling tough times in
      EMS. Interview by Raphael M Barishansky.

PMID- 19856776
TI  - Squeeze me tighter. Will healthcare reform happen on the backs of ambulance
      providers?

PMID- 19856777
TI  - Getting down to details. An introduction to the new EMS Education Standards: part
      2.

PMID- 19856778
TI  - Dead man teaching. A unique educational experience in Tennessee--complete with
      cadavers--brought all the domains of learning together.

PMID- 19856779
TI  - Lessons from the battlefield. How technologies and techniques proving themselves
      in combat care may benefit patients of civilian EMS.

PMID- 19856780
TI  - Dealing with downtime. What's the most productive way to spend intervals between
      calls?

PMID- 19856781
TI  - Critical transport issues. Interfacility transportation of a patient on ECMO.

PMID- 19856782
TI  - National award winners. Meet the winners of the 2009 EMS Magazine Gold Award.

PMID- 19856783
TI  - Over-the-counter overdoses. They're easy to obtain and can have dangerous
      effects. Here's what to look for and do...

PMID- 19856784
TI  - Burning issues. By understanding the pathophysiology of burns, providers can give
      patients their best chance at good outcomes.

PMID- 19856785
TI  - Burn injury assessment. An interactive lesson plan for burn injury management and
      care.

PMID- 19856786
TI  - Professional development. Part 8: mentoring the next generation.

PMID- 19856787
TI  - Professional development. The Memphis mentor model.

PMID- 19856788
TI  - MD envy. Willingness isn't competence, no matter how much you want to help.

PMID- 19856789
TI  - Effect of darbepoetin alfa on renal anemia in Japanese hemodialysis patients.
AB  - INTRODUCTION: A long-acting erythropoiesis-stimulating agent named "darbepoetin
      alfa" (CAS 11096-26-7) was recently developed. Though it is already in use
      worldwide, especially in western countries, its efficacy and safety for Asian
      patients have not been well evaluated yet. The purpose of this study was to
      evaluate the efficacy and safety of short-term darbepoetin alfa administration
      for Japanese hemodialysis patients. METHODS: Patients who had undergone
      maintenance hemodialysis were enrolled in this study. The erythropoiesis
      stimulating agent was switched from epoetin alfa (CAS 113427-24-0) to darbepoetin
      alfa so as to control the hemoglobin (Hgb) value between 10 and 12 g/dl. The
      initial conversion ratio was made according to the manufacturer's
      recommendations. The factors relevant to the responsiveness to erythropoiesis
      were analyzed. RESULTS: One hundred and fifty-nine patients with a mean age of
      67.6 years were enrolled. Two months after switching to darbepoetin alfa, the Hgb
      value had increased significantly (10.3 +/- 1.2 to 10.6 +/- 1.4 g/dl). Only iron
      supplementation correlated positively with the change of Hgb. In addition, 14.3%
      of patients had excess Hgb (Hgb > 12 g/dl) at the end of the study period, but
      only 5.6% patients at the run-in. Serious cardiovascular disease did not occur
      during the study period; however, the mean systolic blood pressure at the start
      of hemodialysis increased significantly and there was no correlation between the
      change of Hgb value and blood pressure. CONCLUSION: Darbepoetin alfa increases
      the Hgb value effectively in Japanese hemodialysis patients. Although no serious
      adverse events were apparent in our short-term analysis, the incidence of
      hypertension and excessive increase of the Hgb value must be noted.

PMID- 19856790
TI  - Pharmacokinetics and bioequivalence study of two cetirizine hydrochloride
      formulations in healthy Chinese male volunteers.
AB  - The pharmacokinetics and relative bioavailability/bioequivalence of two
      formulations of cetirizine hydrochloride (CAS 83881-51-0) were assessed in this
      paper. Using a two-treatment, two-period, two-sequence, randomized crossover
      design, test and reference formulations were administered as individual single
      doses to 18 Chinese healthy male volunteers under non-fed conditions, with a 7
      day washout period between dosing. Fourteen blood samples were drawn from each
      subject over a 34-h period. Cetirizine concentrations in plasma were determined
      by a validated high performance liquid chromatographic-ultraviolet (HPLC/UV)
      assay, and pharmacokinetic parameters, Cmax, AUC(0-t), AUC(0-infinity) and t1/2
      were calculated from the plasma concentration-time data of each individual and
      during each period by applying non-compartmental analysis. Pharmacokinetic data
      for test and reference formulations were analyzed statistically to test for
      bioequivalence of the two formulations. After oral administration the values of
      Cmax, tmax, t1/2, MRT, AUC(0-t), AUC(0-infinity) for test and reference
      formulations were 0.80 +/- 0.14 and 0.80 +/- 0.23 microg/ml, 0.8 +/- 0.4 and 1.1
      +/- 0.7 h, 7.59 +/- 0.68 and 7.63 +/- 0.93 h, 10.59 +/- 0.94 and 10.92 +/- 1.26
      h, 6.00 +/- 1.04 and 5.98 +/- 1.39 microg x h/ml, respectively. ANOVA and CI test
      showed no significant (p > 0.05) variation in these pharmacokinetic parameters of
      test and reference formulations. When the AUC(0-t) values for both formulations
      for natural log-transformed data were compared, the test formulation showed a
      bioavailability of 100.9 +/- 7.7%, as compared to the reference formulation.
      These values are within the acceptance limit of 80-125%. No adverse events were
      observed in any of the subjects during the two runs of the study. Both clinical
      and laboratory parameters of all subjects showed no clinically significant
      changes. This study shows that both formulations were well tolerated and the test
      formulation can be considered a pharmaceutically and therapeutically equivalent
      alternative to the reference formulation.

PMID- 19856791
TI  - Effects of increasing the dose of pravastatin on serum adiponectin level in
      Japanese mild hypercholesterolemic and hypertensive patients.
AB  - The plasma level of adiponectin (CAS 1070484-33-1), known as an anti-atherogenic
      adipocytokine, inversely correlates with the progression of atherosclerosis. The
      reported effects of statins on the serum level of adiponectin include significant
      increases in the adiponectin levels caused by pravastatin (CAS 81131-70-6). In
      this study, increasing the dosage of pravastatin was investigated to determine
      whether it had a clearly favorable effect on the adiponectin level in
      hypercholesterolemic patients. A total of 26 mild hypercholesterolemic and
      hypertensive patients were enrolled in this study. The patients were initially
      treated with pravastatin 10 mg/day for 6 months or more, and then increased to
      pravastatin 20 mg/day. Serum adiponectin, cholesterol fractionated components,
      and lipoprotein components were evaluated after 6 months. Increasing the dose of
      pravastatin from 10 to 20 mg/day caused the low-density lipoprotein cholesterol
      levels to decrease (from 130 to 104 mg/dL, p < 0.001), and thereafter the serum
      adiponectin levels, particularly the high-molecular-weight adiponectin levels
      significantly increased (from 10.9 to 12.6 microg/mL, p = 0.022; from 6.6 to 7.6
      microg/mL, p = 0.022, respectively). Pravastatin increased the serum adiponectin
      level after increasing the dosage from 10 to 20 mg/day. It remains possible,
      however, that the difference was due not only to pharmacologic effects, but also
      to other specific characteristics such as the subject characteristics, viz.;
      race, body size, high-density lipoprotein cholesterol, etc.

PMID- 19856792
TI  - Pharmacokinetics and bioequivalence study of a fixed dose combination of
      rabeprazole and itopride in healthy Indian volunteers.
AB  - The aim of the present study was to compare the pharmacokinetics of rabeprazole
      (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a
      rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy
      human volunteers. The bioequivalence of two formulations (test and reference) was
      determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years;
      weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two
      treatment crossover study. Both formulations were administered orally as a single
      dose, with the treatments separated by a washout period of 1 week. Rabeprazole
      and itopride plasma levels were determined by a validated HPLC method using UV
      detection. The formulations were compared using the pharmacokinetic parameters
      area under the plasma concentration-time curve (AUC(0-t)), area under the plasma
      concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma
      concentration (Cmax). General linear model (GLM) procedures were used in which
      sources of variation were subject, treatment and period. The results indicated
      that there were no statistically significant differences (P > 0.05) between the
      logarithmically transformed AUC(0-infinity) and Cmax values between test and
      reference formulation. The 90% confidence interval for the ratio of the
      logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the
      bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole
      and itopride test and reference formulations was 98.24 and 93.65%, respectively.

PMID- 19856793
TI  - Pharmacokinetics of isoxsuprine hydrochloride administered orally and
      intramuscularly to female healthy volunteers.
AB  - Isoxsuprine (1-(4-hydroxyphenyl)-2-(1-methyl-2-phenoxyethylamino)-1-propanol, CAS
      395-28-8) is a peripheral vasodilator that also stimulates beta-adrenergic
      receptors. It causes a direct relaxation of vascular and uterine smooth muscles
      and produces positive inotropic and chronotropic effects. It is widely used to
      arrest premature labour and miscarriage. The aim of this trial was to investigate
      the pharmacokinetics of isoxsuprine hydrochloride administered orally to healthy
      young female volunteers as an extended-release formulation at the doses of 30, 60
      and 90 mg compared to 10 mg by i.m. route. A randomised, crossover, four-period,
      multisequence, single-dose design was adopted. Plasma and urine concentrations of
      free and total isoxsuprine were evaluated by tandem mass spectrometry that
      reached a low quantification limit of 1 ng/ml. From plasma concentrations Cmax,
      tmax, AUC(0-t), AUC(0-infinity), t1/2 and Vd and from urine concentration CUE(0
      24h) were evaluated by the non-compartmental model. The free drug was present
      only in plasma after i.m. route, whereas total isoxsuprine, namely the drug after
      an enzymatic hydrolysis of the conjugate form, was detected in all plasma and
      urine samples. The distribution volume of the free drug proved to be 2.5 times
      higher than that of total isoxsuprine, which indicates a good penetration of the
      free drug into tissue compartments. Oral absorption was evaluated from the
      p.o./i.m. percentualized ratio of AUC and CUE and proved to be on average around
      51%, being linearly correlated with the three doses administered. The oral
      absorption proved to be sustained as expected from the zero-order kinetics of the
      drug release from the core of the extended-release formulation. This has
      justified different values of half-life that was on average 2.2 h after the i.m.
      route and around 10 h after the three oral doses. After isoxsuprine
      administration, both oral and i.m. routes, the heart rate increased from baseline
      during the 9 h monitoring period. This was an expected finding attributable to
      the stimulating activity of beta-adrenergic receptors. The tolerability of
      isoxsuprine proved to be very good with all the four administrations performed.

PMID- 19856794
TI  - Pharmacokinetics characterization of liposomal amphotericin B: investigation of
      clearance process and drug interaction potential.
AB  - AmBisome, a liposomal formulation of amphotericin B (CAS 1397-89-3, L-AMB), shows
      different pharmacokinetics from the conventional formulation, amphotericin B
      deoxycholate (D-AMB). To characterize the clearance process of L-AMB, the form in
      which it exists in rat plasma, pharmacokinetics in hepatic or renal failure rats,
      cellular distribution in rat liver, and placental and milk transfer in rat were
      investigated. Furthermore, to predict the drug-drug interaction, in vitro
      metabolism of amphotericin B (AMB) by rat, dog and human liver S9 fraction, and
      effects of L-AMB on drug-metabolizing enzyme systems were investigated. L-AMB was
      found to exist stably as a liposomal form in rat plasma without any notable
      transfer to milk or fetus in rats. After administration to hepatic failure rats,
      the CLtot of AMB decreased to 1/4 and the Vdss decreased to 1/8 compared with the
      control rat case. In contrast, after administration to renal failure rats, plasma
      AUC of AMB did not significantly change compared with sham-operated rats. These
      data suggest that hepatic clearance is the main determinant of the CLtot for L
      AMB. In rat liver, L-AMB was distributed mainly to non-parenchymal cells. In the
      in vitro metabolism study using liver S9 fraction, no metabolite peaks were
      observed. After repeated administration of L-AMB to rats, there was no change in
      parameters related to the drug-metabolising enzyme system in liver microsomes.
      These data demonstrate that clinically significant metabolism-based drug
      interaction with L-AMB should be less likely.

PMID- 19856795
TI  - Bioequivalence study of two azithromycin formulations in healthy subjects.
AB  - The study was conducted to find out whether the bioavailability of a 500 mg
      azithromycin (CAS 83905-01-5) tablet (Zycin, test) was equivalent to that of a
      reference formulation. The pharmacokinetic parameters assessed in this study were
      the area under the plasma concentration-time curve from time zero to 120 h
      (AUCt), area under the plasma concentration-time curve from time zero to infinity
      (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to
      achieve the peak plasma concentration (tmax), and the elimination half-life
      (t1/2). This was a randomized, single blind, two-period, cross-over study which
      included 18 healthy adult male and female subjects under fasting conditions. In
      each of the two study periods (separated by a washout of two weeks) a single dose
      of test or reference drug was administered. Blood samples were taken up to 120 h
      post dose, the plasma was separated and the concentrations of azithromycin were
      determined by a LC-MS/MS method. In this study, the mean AUCt, AUCinf, Cmax, and
      t1/2 of azithromycin from the test drug were 4967.49 ng x h x mL(-1), 5871.74 ng
      x h x mL(-1), 412.14 ng/mL, and 51.32 h, respectively. The mean AUCt, AUCinf,
      Cmax, and t1/2 of azithromycin from the reference drug were 4276.75 ng x h x mL(
      1), 5578.12 ng x h x mL(-1), 419.89 ng/mL, and 51.23 h, respectively. The median
      tmax of he test drug and reference drug were 3.0 h and 2.0 h, respectively. The
      geometric mean ratios (90% CI) of the test drug/reference drug for azithromycin
      were 101.56% (86.61-119.08%) for AUCt, 101.27% (84.97-120.70%) for AUCinf, and
      97.78% (84.50-113.16%) for Cmax. Based on this study, it was concluded that the
      two azithromycin tablets (test and reference drug) were bioequivalent in terms of
      the rate and extent of absorption.

PMID- 19856796
TI  - Substitution of theophylline slow-release formulations according to the rebate
      contracts in the German statutory health insurance.
AB  - On the basis of the rebate contracts between individual statutory health
      insurance funds and pharmaceutical enterprises, the generic substitution of
      prescribed medications is economically attractive and is advocated for statutory
      health insurees in Germany. In addition to the drugs whose substitution can be
      considered to be uncritical, rebate contracts also include controversial
      substances such as the bronchodilator theophylline (CAS 58-55-9), which has a
      narrow therapeutic range and should only be substituted under certain conditions.
      The objective of this article was to check the safety of the substitution of
      theophylline by means of a comparative evaluation of bioequivalence studies
      carried out on theophylline slow-release preparations. A systematic literature
      search was carried out in the MEDLINE database. The search terms used were
      combinations of the following key words: theophylline, generics, bioequivalence,
      substitution, brand and non-brand. In addition, a manual search was performed in
      the reference lists of the relevant articles. Only articles that were published
      between January 1, 1988 and August 30, 2008 were to be included. Five studies
      conformed to the inclusion and exclusion criteria. Two of the studies came to the
      conclusion that the preparations analysed were bioequivalent. In the remaining
      three studies there was no bioequivalence found between the preparations and the
      reference product. Because of the heterogeneity of study outcomes no metanalysis
      could be performed. On the basis of the studies analysed the conclusion can be
      drawn that a theophylline slow-release preparation should only be substituted
      under close monitoring by a physician because of the many factors which can
      adversely affect serum levels, such as the narrow therapeutic range of the active
      ingredient, the patient's metabolisation rate or the different galenics of the
      preparations. Nevertheless, the question remains as to whether the costs saved by
      the rebate contracts would not be significantly outweighed.

PMID- 19856797
TI  - RAC 'time out' a chance to review. Now is a good time to ensure that the right
      technology is in place, before medical necessity reviews are required.

PMID- 19856798
TI  - The challenge to lead change.

PMID- 19856799
TI  - Scripps tackles RAC challenges. Among the lessons learned in pilot project is the
      need for comprehensive revenue-cycle management systems and processes.

PMID- 19856800
TI  - Gateway secures Web 2.0 initiative. Concerned about malware and other security
      issues, Health First settled on a solution that allows IT to set granular,
      flexible internet usage policies for devices, as well as specific users and
      groups.

PMID- 19856801
TI  - Hospital automates revenue-cycle processes. Software is instrumental in helping
      perform root-cause analysis of coding errors and omissions, creating an early
      identification process of clinical practice charge-capture trends.

PMID- 19856802
TI  - Payer leans on wellness, care-management program. Using predictive modeling and
      stratification software, Highmark Blue Cross Blue Shield classifies covered
      members into one of 30 population segments.

PMID- 19856803
TI  - Speech recognition improves EMR ROI. Medical group decided that to be most
      successful with EMR adoption, 100 percent physician population utilization would
      be necessary.

PMID- 19856804
TI  - Improve processes with perioperative EHR. By using electronic records, physicians
      no longer need to rely on nursing staff to interpret written orders or protocols
      appropriately.

PMID- 19856805
TI  - How virtualization can affect the IT budget. Less hardware means fewer physical
      devices to replace, upgrade, maintain and troubleshoot, translating into lower
      costs.

PMID- 19856807
TI  - The healing environment.

PMID- 19856806
TI  - Diabetes and kidney disease.

PMID- 19856808
TI  - Understanding diabetes mellitus and kidney disease.
AB  - Diabetes mellitus is a chronic disease that can cause serious long-term
      complications when blood sugars are not well controlled. Damage to small
      microscopic blood vessels in the kidney that filter out waste products from the
      blood can eventually cause kidney disease. Over time, the kidneys become
      overworked and start to leak. Because the kidneys are good at compensating for
      failing blood vessels, kidney disease produces no symptoms until function is
      almost completely gone. The purpose of this article is to define diabetes
      mellitus, describe appropriate criteria for diagnosis, and explain the term pre
      diabetes. In addition, discussion of the connection between diabetes and kidney
      disease is presented.

PMID- 19856809
TI  - Future trends in diabetes management.
AB  - Since the discovery of insulin in the 1920s, numerous therapeutic and
      technological advances have improved the lives of patients with diabetes
      mellitus. This article reviews recent therapeutic and technological advances and
      future trends in the management of diabetes mellitus. Pancreas regeneration,
      pancreas transplantation, islet transplantation, continuous subcutaneous insulin
      infusion, continuous glucose monitoring, and various medication classes are
      discussed.

PMID- 19856810
TI  - Periodontal disease--the overlooked diabetes complication.
AB  - Periodontal diseases are infectious processes that occur in the presence of
      bacteria, which trigger an inflammatory response. Periodontal disease is
      associated with many medical conditions, including diabetes mellitus and its
      complications (such as kidney disease). It has been described as the "sixth
      diabetes complication" but is often overlooked in routine diabetes management and
      complication screening processes. Proactive, preventative dental and diabetes
      self care, as well as regular dental and diabetes assessment, are important
      management strategies because periodontal disease contributes to the progression
      of impaired glucose tolerance to diabetes mellitus and to hyperglycemia in
      individuals with established diabetes.

PMID- 19856811
TI  - So just what can I eat? Nutritional care in patients with diabetes mellitus and
      chronic kidney disease.
AB  - The balance of nutrition in patients with diabetes mellitus and chronic kidney
      disease is essential to optimum health outcomes. Multiple nutritional parameters
      need to be monitored, including energy balance, protein intake (type and amount),
      mineral control (sodium, potassium, calcium, phosphorus), fluid requirements, and
      coordination of carbohydrates, to achieve glycemic control in diabetes mellitus.
      The nephrology nurse benefits by understanding the multiple nutrition parameters
      required in diabetes mellitus and chronic kidney disease to participate and
      reinforce the complexities of the daily nutritional challenges in coordination
      with a registered dietitian. A comprehensive overview of the nutrition parameters
      in chronic kidney disease and diabetes mellitus is discussed so the question "So
      just what can I eat?" can be answered with greater confidence.

PMID- 19856812
TI  - Perceptions of risk for foot problems and foot care practices of patients on
      hemodialysis.
AB  - Patients with end stage renal disease are recognized as being prone to foot
      problems; however, less is known about this issue from the patient's perspective.
      This qualitative descriptive study explored the perceptions of risk for foot
      problems and foot care practices of patients on hemodialysis. A purposive sample
      of 9 men and women from a large university-affiliated hospital center in Quebec,
      Canada, was used. Three major themes emerged from the semi-structured interviews:
      1) Foot problems are not a serious complication, 2) I am protected from
      developing foot problems, and 3) Taking care of my feet. Patients, including
      those currently suffering from a foot problem, lacked knowledge of their actual
      risk for foot problems. All participants engaged in some form of foot care, such
      as the use of a foot bath and regular moisturizing. Several individuals described
      behaviors that could compromise foot health. Findings suggest that it is
      worthwhile for nurses to elicit patients' actual foot care practices to validate
      those that are appropriate and to address those that are unsafe.

PMID- 19856813
TI  - Strategies for managing diabetes mellitus and chronic kidney disease.

PMID- 19856814
TI  - Correcting iron-restricted erythropoiesis and improving anemia in patients on
      hemodialysis: practical tips that can make a difference.
AB  - In healthy individuals, the body remains in an iron-balanced state. Iron intake
      and loss on a daily basis is minimal, and the majority of iron in the body is
      recycled. However, patients on hemodialysis may have an insufficient supply of
      iron available to the bone marrow for erythropoiesis, a condition known as iron
      restricted erythropoiesis or inflammation-mediated reticuloendothelial blockade.
      This state may occur as a result of an inflammatory process and can limit the
      patient's ability to respond to erythropoiesis-stimulating agents (ESAs).
      Intravenous (IV) iron supplementation may be needed to overcome iron-restricted
      erythropoiesis and improve ESA response. This article focuses on the complex
      relationship among the three I's in anemia management: inflammation, iron
      restricted erythropoiesis, and IV iron treatment.

PMID- 19856815
TI  - Chapter 1. Concepts and principles of quality management.
AB  - Quality and continuous quality improvement play a key role in health care. The
      specialty of nephrology is no exception. Quality and its ongoing improvement is
      the right thing to do because of the human lives at stake. It is also the
      business thing to do because of regulatory compliance and pay-for-performance
      expectations. Quality improvement in health care is not a new concept. CQI,
      however, has at times been misunderstood, under used, and even misused. It is not
      simply paperwork to be completed for regulatory or corporate compliance. It is a
      time-tested, common-sense approach to quality that really works in helping to
      identify improvement needs, develop solutions, and assess results of actions
      taken, both in the short and long term. When all is said and done, CQI is a
      mindset--a way of thinking about and practicing for quality.

PMID- 19856816
TI  - Overheated dialysate: a case study and review.
AB  - Overheated dialysate has been reported as a cause of fatal hemolysis, both acute
      and chronic. However, published incidents are several decades old and only
      include cases where the dialysate was overheated above 47 degrees C or where the
      temperature was not reported This case study examines an incident where a faulty
      plumbing valve introduced hot water into a cold line used exclusively ror
      inpatient dialysis in an intensive care unit, causing the dialysate temperature
      to raise as high at 39.8 degrees C before the treatment was terminated early. A
      review of the literature demonstrates that while thermal hemolysis only occurs in
      temperatures of at least 47 degrees C, patients exposed to overheated dialysate
      at much lower temperatures may still be at risk for hyperthermia and heat stroke.

PMID- 19856817
TI  - Nursing shortage still looms. Nursing schools warn that ease in nurse shortage is
      an illusion.

PMID- 19856818
TI  - Scleroderma.

PMID- 19856819
TI  - Why are chemicals a health problem?

PMID- 19856820
TI  - And then there were none.

PMID- 19856821
TI  - Patient-physician e-mail communication revisited a decade later: an OKPRN study.
AB  - In private community-based primary care practices in Oklahoma, approximately two
      thirds of patients now have access to a computer and e-mail either at home or
      work. A substantial majority would like to use e-mail to communicate with their
      primary care clinicians. Since 1997, rural patients have caught up with urbanites
      in their access to computers.

PMID- 19856822
TI  - Evaluating health care reform in the tradition of medical science.

PMID- 19856823
TI  - Which adults should be tested or treated for vitamin D deficiency?

PMID- 19856824
TI  - Part six: The role of narrative in the everyday practice of medicine ethics and
      mistakes in the everyday practice of medicine.

PMID- 19856825
TI  - To screen or not to screen, part III: what's new in obstetrics and genetics?

PMID- 19856826
TI  - The first-trimester screen in clinical practice.
AB  - The first-trimester screen combines nuchal translucency measurement and serum
      levels ot PAPP-A and beta-hCG between 11 and 13 weeks gestational age which can
      be used to calculate the risk of fetal Trisomy 21 and 18. Although these
      trisomies are the most common conditions detected, recognition of increased risk
      for several other fetal conditions and maternal complications have also been
      documented. A common misconception is that requesting this test implies that the
      patient will automatically terminate an affected fetus. Although termination may
      be one option, it is not the primary goal of this screen. If this screen results
      in the discovery of an abnormal fetus, the patient is allowed maximal time for
      privacy, formulation of a medical management plan, preparation for caring for a
      child with special needs, personal research and consultation with appropriate
      pediatric subspecialists. This test also decreases maternal anxiety throughout
      pregnancy. The American College of Obstetricians and Gynecologists (ACOG)
      recommends that all women, regardless of maternal age and risk factors, be
      offered this screening test. This paper addresses how the test is performed,
      management of abnormal findings, risk factors and detection rates.

PMID- 19856827
TI  - Changes in end-of-life attitudes and actions over time: one community in 2004
      2005.
AB  - INTRODUCTION: The purpose of this research is to explore changes in end-of-life
      (EOL) attitudes and actions among Sioux Falls, South Dakota, residents between
      August 2004 and August 2005. METHODS: Questionnaires were sent to 5000 randomly
      selected Sioux Falls households (2004) and to 10,000 South Dakota households
      (2005), where a subset from the city allowed researchers to compare Sioux Falls
      residents' attitudes and actions over time. Data were entered into the computer
      using the Statistical Package for the Social Sciences, and bivariate analyses
      were conducted using Chi Square, where p < or = .05 was used to assess
      statistical significance. RESULTS: Compared to the 2004 sample, respondents in
      2005 were more likely to have taken actions to ensure their EOL preferences were
      honored, knew more about hospice and were more polarized in their views about EOL
      care. Consistencies in EOL preferences were also revealed. CONCLUSIONS:
      Longitudinal analysis suggests that public discussion of EOL issues makes a
      difference in the public's attitutdes and actions. Implications for future
      research are discussed.

PMID- 19856828
TI  - Ambulatory blood pressure monitoring: another tool for the diagnosis and
      management of hypertension.
AB  - Office BP measurements are unable to detect 24-hour variability in blood
      pressure. ABPM is a tool that can assess BP at extended intervals, aiding in the
      diagnosis of white coat hypertension, masked hypertension and nighttime non
      dipping status. Value exists in knowing a patient's BP variability so the
      appropriate treatment regimen can be determined or overtreatment can be avoided,
      all in an effort to decrease a patient's cardiovascular risk and potential for
      negative outcomes.

PMID- 19856829
TI  - Preventive screening in physician practices.

PMID- 19856830
TI  - Quality...When our system doesn't demand it.

PMID- 19856831
TI  - Changes to HIPAA under the HITECH Act.

PMID- 19856832
TI  - Aging chimp.

PMID- 19856833
TI  - [Harald zur Hausen--a scientist with passion. Vaccine against cervical cancer].
AB  - The profile of Harald zur Hausen, German virologist and Nobel-Prize winner for
      medicine in 2008, is presented in the context of his life and scientific
      achievements. The studies of zur Hausen on oncogenic viruses submitted a finding
      that chronic infection with certain highly invasive human papilloma viruses
      (HPV16 and HPV18 types) causes cervix carcinoma. The discovery was a starting
      point to successful construction of biosynthetic preventive vaccines against this
      carcinoma, such as "Gardasil" and "Cervarix".

PMID- 19856834
TI  - [Visceral leishmaniasis as a threat for non-endemic countries].
AB  - Global warming, globalisation, and constantly increasing number of people
      involved in long-distance tourism and travel to exotic destinations are likely to
      increase the number of cases of exotic diseases "imported" to nonendemic
      countries. One of the often forgotten and neglected diseases has been visceral
      leishmaniasis (VL or kala-azar). The disease is endemic to 62 countries, with
      India and Sudan accounting for the majority of the cases. It is typically fatal
      if left untreated. Each year about 500 000 new cases are reported worldwide, and
      50 000 die as a result of the disease. Kala-azar is present in the Mediterranean
      Europe and 70% of cases are imported to non-endemic countries of European Union
      from that area. Immunocompromised status of patients, like HIV carriers are the
      principal prospective target for kala-azar. HIV/VL-coinfected patients have
      significantly higher relapse rates and decreased life expectancy. There is no
      formal system of reporting imported cases in Europe, except from Germany. In non
      endemic countries, including Poland, there is usually the substantial delay
      between the onset of symptoms and the final diagnosis, with an average exceeding
      3 months. This fact suggests that physicians are not familiar with leishmania
      infections. Despite progress in vaccine development, the only way to prevent the
      infection is avoiding sandfly bites. Mosquito nets, wearing appropriate clothes
      and repellents containing DEET (diethyl toluamide) can reduce number of bites and
      protect also from the other vector-borne diseases like malaria or dengue.
      Education concerning kala-azar risk and ways of the disease prevention is a
      needed for tourists and the other travelers.

PMID- 19856835
TI  - [Anisakis simplex larvae from the Baltic herring as tag organisms in biological
      and fisheries research. I. Baltic herring and A. simplex nematodes: the models of
      parasitic infection and fish migration tags].
AB  - Models relating infection intensity with Anisakis simplex larvae to the fish
      length and weight were developed and applied to estimate the asymptotic size of
      herring. Generalized linear models (GLM) were used to analyse the prevalence and
      intensity of infection as dependent on time and area of sampling and the
      biological parameters of fish. For the characterization of herring populations in
      the southern Baltic, two complementary approaches were used: morphometric and
      meristic analyses to quantify the body shape of herring and the presence of
      parasites as fish migration tags.

PMID- 19856836
TI  - [Anisakis simplex larvae from the Baltic herring as tag organisms in biological
      and fisheries research. II. Host and parasite acetylcholinesterases].
AB  - Acetylcholinesterase (AChE) activity in the tissues of host and the parasite and
      the impact of carbofuran, a carbamate pesticide on the AChE activity in A.
      simplex larvae was investigated. Generalized linear models (GLM) were used for
      modeling enzymatic activity in herring and A. simplex nematodes.

PMID- 19856837
TI  - [An attempt of experimental infection of fishes and chickens with invasive larvae
      of Elaphostrongylus cervi (Nematoda, Protostrongylidae)].
AB  - Elaphostrongylus cervi is a parasite of skeletal muscles and central nervous
      system of wild and farm red deer in Europe and Asia. Numerous species of
      terrestrial snails can be its intermediate hosts. Considering the fact that
      invasive larvae of E. cervi are released by deer to the external environment in
      huge numbers, fishes and birds can be accidentally infect by them. In this study
      the development of larvae E. cervi in those nonspecific hosts was discussed. It
      was determined that invasive larvae of E. cervi in the digestive tract of fish do
      not penetrate the intestinal wall, do not develop any further, and are probably
      digested. Similarly, those larvae given to chicken are also incapable of breaking
      the gut barrier and are digested. In all infected animals, the phenomenon of
      parathenia has not been observed and the meat of the animals studied poses not
      threat to humans.

PMID- 19856838
TI  - [The way of penetration of first stage larvae of Elaphostrongylus cervi
      (Nematoda, Protostrongylidae) to the intermediate host and their development to
      the invasive stage].
AB  - The aim of the study was the way of penetration of the first stage larvae of
      Elaphostrongylus cervi to the intermediate host and their development to the
      invasive stage. The first stage larvae of E. cervi penetrate to the body of a
      snail by the epithelium of its foot, and localise in tissue of muscles. The
      period of their development to the second stage is 7 to 9 days, and to the third
      stage is 21 to 28 days.

PMID- 19856839
TI  - [The first record of the lungworm, Metastrongylus asymmetricus (Noda, 1973), in
      the wild boar from Poland].
AB  - A total of 17 wild boars (Sus scrofa) shot in the Miechow hunting area (southern
      Poland) during two consecutive winters of 2008, were surveyed for the presence of
      lung nematodes of the genus Metastrongylus. The animals were necropsied, their
      lungs removed, divided into smaller parts and examined along the bronchial tubes.
      The parasites found were identified based on their morphologic characters. The
      prevalence of the lungworms reached 76.5%, and all of the 13 infected animals
      harboured two (one boar) or more parasite species. The mean number of parasites
      in an individual boar was 58.7, ranging from 6 to 250 specimens. Out of 250
      identified lungworms, 48.8% was identified as M. pudendotectus, 32.8% were M.
      elongatus, and 14.0% belonged to M. salmi, whereas 4.4% (i.e. 10 females and 2
      males) were M. asymmetricus. Until recently, only four Metastrongylus species
      have been recorded from Poland, namely M. elongatus, M. pudendotectus, M. salmi
      and M. confusus. The presently reported finding of M. asymmetricus constitutes
      the first record of this species in Poland.

PMID- 19856841
TI  - Gregarines (Apicomplexa) and microsporidians (Microsporidia) of native and
      invasive gammarids (Amphipoda, Gammaroidea), occurring in Poland.
AB  - The goal of our study was to recognize microparasites of alien gammarids
      inhabiting Polish inland and coastal waters versus those infecting local species.
      Twenty two localities including the Vistula, Oder and Bug Rivers, Vistula Lagoon,
      Goslawskie Lake, littoral of the Baltic Sea, as well as small rivers draining
      directly to the sea were investigated. In total, over 5000 individuals of 14
      species of gammarids were collected and analyzed using light and electron
      microscopy. The studies have revealed five named and seven unnamed species of
      gregarines (Apicomplexa, Gregarinidae) as well as three named and seven unnamed
      species of microsporidians (Microsporidia, Nosematidae, Thelohaniidae) infecting
      six native and four invasive gammarid host species. All the above microparasites
      were new to Poland. Four species of gregarines (Uradiophora ramosa, U.
      longissima, Cephaloidophora similis, C. mucronata) and four microsporidians
      (Nosema dikerogammari, N. pontogammari, Thelohania sp. 2, Thelohania sp. 5) were
      associated with hosts of Ponto-Caspian origins. Evidently, these microparasites
      were transported to the area through the range expansion of their invasive hosts.
      Gregarines Cephaloidophora sp. 1 and Uradiophora sp. 1 were registered only in
      North American Gammarus tigrinus. Uradiophoera ramosa infects Ponto-Caspian (P.
      robustoides, D. villosus) and North-Americah hosts (G. tigrinus).

PMID- 19856840
TI  - [The occurrence of Cryptosporidium spp. in synanthropic flies in urban and rural
      environments].
AB  - This study was carried out to determine the role of non-biting synanthropic flies
      as carriers of Cryptosporidium spp. oocysts in the vicinity of the city of Gdansk
      (NE Poland). In 2001-2003, flies were collected from three breeding sites: cow
      sheds and meadows in the Bystra cattle farm and municipal landfill Szadolki using
      inhaustors (aspirators) and entomologic nets. A total of 2358 specimens of the
      families: Muscidae (n = 1598), Calliphoridae (n = 739) and Sarcophagidae (n =21)
      were collected and analysed in 249 pools consisted of 9.5 insects, in average.
      Microscopic examination was used to detect Cryptosporidium spp. oocysts in the
      fly faeces deposited on the glass microscope slides and stained by Zhiel-Nielsen
      method. The mean number of faecal droplets per one glass slide was 11.5. Ooocysts
      of Cryptosporidium spp., stained from light pink to bright red, were found in fly
      faeces deposited on 25 (27.5%) of 91 glass slides checked. The highest prevalence
      of the pathogen was observed in faecal droplets deposited by flies collected in
      municipal landfill (50% investigated slides). DNA of Cryptosporidium spp. was
      extracted from the surface eluants of flies and/or their gut homogenates and
      purified. Then extracts were examined by PCR using CPB-DIAGF and CPB-DIAGR
      primers amplifying a variable region SSU-rRNA of all Cryptosporidium species.
      Altogether 387 isolates, 228 from surfaces and 159 from gut homogenates, were
      obtained from 249 pools of flies and analyzed. A specific 435 bp fragment of DNA
      was obtained in 49 (12.7%) lysates tested. In 10.4% pools, DNA of the pathogen
      was detected only in the surface eluants while in 7.6% only in gut extracts. In
      the case of two pooled samples (0.8%) Cryptosporidium spp. was found in both
      types of lysates. In total, Cryptosporidium spp. was detected in 47/249 pools of
      flies (18.9%). Assumed that each positive pool contained just one infected fly,
      the percentage of specimens able to oocysts transmission were calculated at the
      minimal level 2.0% (n = 47/2358). The result confirm that synanthropic flies can
      harbour oocysts of Cryptosporidium spp. both externally and internally, and
      disseminate them mechanically in the environment. Therefore, under unsanitary
      conditions they could be involved in the transmission of human and animal
      cryptosporidiosis.

PMID- 19856842
TI  - The occurrence and ultrastructure of Trypanosoma (Herpetosoma) lewisi (Kent,
      1880) Laveran and Mesnil, 1901, the parasite of rats (Rattus norvegicus) in
      Poland.
AB  - This study reports the light and electron microscopic examination of Trypanosoma
      (Herpetosoma) lewisi (Kent, 1880) Laveran and Mesnil, 1901, isolated from rats
      (Rattus norvegicus) from Poland. Bloodstream trypomastigotes were identified
      morphometrically from 100 specimens collected from three naturally infected rats
      Rattus norvegicus. Body length ranged from 15.45-23.64 microm and width from 1.3
      2.32 microm while the free flagellum was 8.1 microm long. Electron microscopic
      study of bloodstream trypomastigotes exhibited typical ultrastructural features
      similar to those of other stercorarian trypanosomes. The presently determined
      morphological data have been compared with those provided by other authors.

PMID- 19856844
TI  - [Usage of the Hoyer's medium for diagnostics and morphological studies of some
      parasites].
AB  - Various modification of the mixture of gum arabic with chloral hydrate can be
      used for mounting of small arthropods as well as some helminths. However, in
      diagnostic laboratories in Poland they seem to remain unknown. The authors of
      current work present examples of the Hoyer's medium application. The medium has
      been composed according to the initial, given by Hoyer, hundred-years-old recipe,
      which was the root of all other, later used recipes. Hoyer's medium is universal
      in action and very comfortable to use in slides for microscope investigation. It
      gives the immediate light-through effect, so it can be helpful in fast
      diagnostics. At the same time it allows to store the slides for a relatively long
      time e.g. with education purpose.

PMID- 19856843
TI  - [A study on the occurrence of West Nile virus in mosquitoes (Diptera: Culicidae)
      on the selected areas in Poland].
AB  - West Nile virus (WNV), the etiologic agent of West Nile Fever (WNF), an emerging
      infectious disease that lately has been rapidly extending its range of occurrence
      from Africa to Middle East, and to Asia and Southern Europe. In Europe, cases of
      isolating WNV from mosquitoes representing four genera have been reported from
      Romania, Portugal, France, southern Russia and what is the most important, from
      Poland's neighbouring countries as the Czech Republic, Slovakia and southern
      Ukraine. These data, as well as human and equine cases in the Czech Republic and
      Belarus, support hypothesis that WNV has already been present also in Poland, the
      more so, specific antibodies were detected in the sera of birds collected at the
      Kampinos and Bialowieza Primeval Forests and in human from the vicinity of
      Bialystok. Mosquitoes were collected in 2004-2009 at indoor and outdoor
      collection sites in districts: Kujawsko-Pomorskie, Mazowieckie, Podlaskie and
      Warminsko-Mazurskie. In total 15400 female mosquitoes were collected in the cow
      sheds and overwintering in the cellars, and from human bait and CO2 traps.
      Mosquitoes were sorted by the collecting site, species and sex, and placed in
      pools of not in more than 50 specimens in special mixture of phenol and
      chaotropic salts and frozen in -20 degrees C. Altogether, 15400 females were
      examined. Total RNA were extracted according to protocol of A&A Biotechnology. RT
      reaction was performed with random primers and 217-nucleotide fragment from the
      NS5 coding sequence was amplified by heminested PCR. PCR products were analysed
      on 1.5% agarose gel. The predominant species was Culex pipiens, accounting for
      over 42% of total insects collection. All obtained results were negative. Further
      investigations are needed.

PMID- 19856845
TI  - [48. Day of Medical Parasitology "reservoirs of parasites and pathogenic fungi in
      human population and the environment"].

PMID- 19856846
TI  - [Genotypic and phenotypic methods for testing Mycobacterium tuberculosis
      sensitivity to antibiotics].

PMID- 19856847
TI  - [Involvement of soluble mediators of inflammation in the pathogenic agent
      interaction--immune system in acute bacterial meningitis].
AB  - Acute Bacterial Meningitis is a medical emergency, which warrants early diagnosis
      and aggressive therapy, which in most cases must be initiated as an "empirical"
      treatment. Such an approach needs permanent epidemiological surveillance due to
      the major variability of the etiological agents depending upon time, geographical
      areas and demographic characteristics of the population. A program for the
      surveillance of meningitis is in progress in Romania, but the available clinical
      inbformation is incomplete and not well documented by paraclinical data, poorly
      reflecting the real incidence of the disease. The specific anatomic localization
      of the disease has major influences on the antiinfectious immune response.
      Inflammation is involved in the disease pathogenesis, especially in promotion and
      evolution of neurological sequelae (neuronal demyelinisation and degeneration)
      even in case of pathogen clearance following antimicrobial therapy. Activation of
      the immune response in a immunologically "privileged "region can lead to the
      break of tolerance and induction of autoimmunity (neuronal degenerescence). On
      the other hand, an efficient immune response is necessary for the clearance of
      pathogenic agents. A detailed investigation of the interaction between pathogenic
      agents and the immune system in relation to the particular meningeal localization
      and also a study on the involvement of soluble mediators of inflammation
      (cytokines, chemokines) in the pathogenesis of meningitis might prove useful for
      differential diagnosis (viral or "aseptic" meningitis) and also for elucidating
      the mechanisms which that underlie the disease pathogenesis/neurological
      complications.

PMID- 19856848
TI  - [Aminoglycoside resistance of enterobacteria isolated from urinary infections in
      surgical departments].
AB  - The aim of the study was to determine the aminoglycosides resistance of
      Enterobacteriaceae strains isolated from urocultures. Identification of the germs
      was performed by the API system (BioMerieux) and susceptibility tests was
      performed by disk-diffusion test (CLSI standards) and with API strips. For
      detecting the resistance to aminoglycosides we used gentamicin, tobramycin,
      netilmicin and amikacin. From 2500 urine samples we isolated 673 microbial
      strains, from which 531 were Enterobacteriaceae, especially E. coli, 57.62% and
      Klebsiella pneumoniae pneumoniae, 27.68% strains. We observed natural maintained
      sensibility to aminoglycosides at 55.17% from all the strains we have studied The
      high prevalence of aminoglycosides resistance of Enterobacteriaceae strains is
      explained by prolonged antibiotic therapy of patients with invasive diagnostic
      and therapeutic procedures. A rational policy in prescribing antibiotics in this
      department is therefore mandatory.

PMID- 19856849
TI  - [Antibiotic resistance patterns in Acinetobacter spp. strains isolated from
      hospital environment].
AB  - INTRODUCTION: The Acinetobacter species are ubiquitary germs isolated more and
      more frequently, Acinetobacter baumannii being currently considered the second
      strictly aerobic microorganism involved in the ethiology of severe nosocomial
      infections. Acinetobacter baumannii is usually encountered in surgery and
      intensive care units, especially in patients with depressed immunity, in which
      various locations are possible, the most frequvent being the respiratory tract
      infections, urinary tract infections and bacteriemia. MATERIAL AND METHOD: The
      study used 52 strains of Acinetobacter spp. isolated from 1131 biological samples
      (bronchial aspirat, urine, wound secretion, blood, pus, CFS) obtained from the
      patients of the Timisoara Country Hospital. Identification of germs was performed
      using the API (BioMerieux) system, and the antibiotics sensitivity testing was
      made by disk diffusion testing (Kirby-Bauer), with automatic reading and
      phenotyping through the Osiris Evolution (BioRad) system. RESULTS: The study of
      resistance to beta-lactamines has pointed out the predominance of penicillinase
      and cephalosporinase producing strains, 55.77% of the tested ones being part of
      this phenotype. 90.38% of the strains were resistant to one or more
      aminoglycosides. Of the tested strains 76.93% were resistant to fluoroquinolones,
      86.54% to trimethoprim-sulphamethoxazole, and only 21.15% to tethracycline.
      CONCLUSIONS: Among the emerging pathogens involved in the nosocomial infections,
      Acinetobacter baumannii strains have become, in the past decades, a real health
      issue, due to the variety and seriousness of clinical symptoms. Through the
      constant increase of the cases number, and the difficulty of applying an
      effective treatment, the above-mentioned strains showed a multiple resistance to
      antibiotics.

PMID- 19856850
TI  - [Hydatidosis relapse in children--clinical and epidemiological study].
AB  - This study is a retrospective inquiry among children operated for hydatid cyst
      which were diagnosed with at least one relapse episode. The study-group consisted
      of 160 children out of which 110 were submitted to at least one surgical
      procedure and 35 out of 110O presented hydatidosis relapses. The post-operative
      monitorization of children with hydatidosis must be extended over a 2-year-period
      (69.29%) time during which most of the relapses occur. The organs being most
      frequently affected are primary the liver and secondary the lung. The secondary
      hydatidosis is more frequent "at distance" from the residual cavity than "in
      situ". The parasitic control is centered on the imagistic test: abdominal
      ultrasound, lungradiography and the serological surveillance of specific
      antibodies of IgG class which can remain positive during the whole life with
      decreasing titers in time. The antiparasitic treatment pre- and post- operative
      can complete the therapeutic schedule in the case of hydatidosis in order to
      assure the recovery.

PMID- 19856851
TI  - [Effect of air pollution upon the hospitalization for acute lower respiratory
      tract infections among the Bucharest municipality's residents].
AB  - OBJECTIVE: Assessment of the short-term association between exposure to outdoor
      air pollution and hospitalization for lower respiratory tract infections (LRTI)
      in the Bucharest municipality'spopulation. MATERIALS AND METHODS: Relation
      exposure--health effect has been explored through linear regression upon time
      series, where the independent variable was represented by daily levels of
      nitrogen dioxide (NO), carbon monoxide (CO), sulfur dioxide (SO2) and ozone (O3)
      from atmospheric air of Bucharest municipality whereas the dependent variable has
      been represented by daily frequency, by age groups, of Bucharest municipality
      residents, hospitalized during the year 2007for LRTI (ICD-10 codes: J12-J22).
      RESULTS: In the year 2007, through linear regression we found high correlations
      (p < 0.01) between the following variables: (a) daily atmospheric concentrations
      of NO2, CO and SO2, (b) daily frequencies of hospitalizations for LRTI by age
      group and (c) daily air levels of three of the above mentioned pollutants and the
      age-specific frequencies of patient hospitalization for LRTI. The O3 daily air
      levels have been correlated (p < 0.01) only with the daily air levels of SO2 and
      CO but wasn't correlated to NO2 air level or with the health effect studied
      CONCLUSIONS: in the Bucharest municipality, the study demonstrated robust
      associations between the atmospheric pollutants' levels and daily frequencies of
      hospital admissions for LRTI. Through inference the results suggests that the
      interventions for environment control which will result in decreasing of the
      pollution level with NO2, CO and SO2 might be associated with decreasing the
      frequency of hospitalization for LRTI and consequently with preserving the
      resources allocated for health.

PMID- 19856852
TI  - [Evaluation of iron, fluoride and iodine concentrations in underground water in
      some counties in Romania].
AB  - AIM: To compare the underground water mineral composition in iron, fluorine and
      iodine from different sources, with variable locations in Romania. METHODS: It is
      a lab study based on Hanna Instruments C99 colorimeter used for our tests, that
      follows the levels of mineral parameters from water samples from several
      underground water supplie sources from 10 different romanian counties. RESULTS:
      It were significant differences between sources from different counties, and also
      from different sources in the same county, regarding minerals levels in water and
      also comparing to admitted levels. The most various data were related to fluorine
      and iodine levels in water samples and risk of exposure by deficiency.
      CONCLUSION: It is important to know the importance of supply water monitoring, to
      evaluate both the drinking water quality parameters and mineral composition, in
      order to estimate the influence on health status of long shut consumer
      population.

PMID- 19856853
TI  - [Laboratory diagnosis of tuberculosis--(1) Microbiological diagnosis].

PMID- 19856854
TI  - [Group B streptococci and pregnancy. Strategies for the prevention of perinatal
      disease].

PMID- 19856855
TI  - [Enteric patotypes of Escherichia coli involved in diarrhea disease].

PMID- 19856856
TI  - [Factors incriminated in the onset of emerging infections].

PMID- 19856857
TI  - [Activities in view of implementing the International Health Regulations 2005].

PMID- 19856858
TI  - [International Health Regulations (2005)].

PMID- 19856859
TI  - The risk factors of parenteral nutrition-associated cholestasis in preterm
      infants.

PMID- 19856860
TI  - Pediatric critical care--a new frontier.
AB  - Pediatric intensive care is now a subspecialty of pediatric medicine. Different
      pathologic and physiologic processes occur in pediatric patients who require
      intensive care. Thus, the faculty and staffing requirement differ in many aspects
      from those of adult intensive care units (ICUs). In Taiwan, pediatric intensive
      care is relatively less developed than adult care. However, thanks to the
      implementation of national health insurance and increasing emphasis of children's
      health, the scope and quality of pediatric intensive care has widened and rapidly
      improved. Research has shown that full time in-ICU staffing and patient care will
      result in improved outcomes for critically ill pediatric patients. In this
      article, we review the literature and recent advances in pediatric intensive
      care; we also outline the challenges arising. Special emphasis was made to the
      clinical context of Taiwan.

PMID- 19856861
TI  - Etiologies of spontaneous pneumomediastinum in children of different ages.
AB  - BACKGROUND: Spontaneous pneumomediastinum (SPM), while rare, is probably
      underestimated in children. Treatments for SPM target the underlying disease and
      trigger factors. This study aimed to analyze the etiology of SPM in different age
      groups. METHODS: A total of 18 children with SPM were analyzed in the Children's
      Medical Center at China Medical University Hospital between 1997 and 2007.
      RESULTS: The incidence of SPM in children was 1:8,302 patients at the Department
      of Pediatric Emergency Medicine. A bimodal peak in incidence occurred in those
      younger than 4 years old and in those aged 15-18 years. Characteristic symptoms
      were dyspnea (77.8%), followed by chest pain (66.7%) and neck pain (44.4%);
      common specific physical signs were subcutaneous emphysema (55.6%) and Hammer's
      sign (11.1%). Trigger factors were infection (44.4%), with a mean age of 5.8+5.0
      years, and diabetic ketoacidosis (5.6%), with a mean age of 18 years. Idiopathic
      SPM accounted for 50.0% of patients, with mean age 14.4 +/- 1.8 years. In terms
      of the age distribution, five (27.8%; males/females=4:1) preschoolers (<6 years
      old) developed SPM, mostly due to infectious disease. Two girls aged less than 10
      years developed asthma in later years. All eight male adolescents (> or =10
      years) developed SPM due to idiopathic factors. Of nine boys with idiopathic SPM,
      six underwent strenuous exercise before developing SPM. Mean hospitalization was
      7.9 +/- 11.5 days and 11 (61.1%) patients needed intensive care. Nearly all of
      the patients had complete resolution on chest radiography before discharge.
      CONCLUSION: Clinicians should be alert to the risk of SPM based on the presence
      of these symptoms. The etiology of SPM varies with age. Treatment of SPM must
      target the trigger factors or the underlying disease.

PMID- 19856862
TI  - Gastrointestinal polyps in children.
AB  - BACKGROUND: Gastrointestinal polyps are common in children. The purpose of this
      study was to review the clinical manifestations, diagnostic procedures,
      endoscopic findings, management, pathology, and recurrence of gastrointestinal
      polyps in children at Mackay Memorial Hospital. METHODS: We retrospectively
      reviewed the charts of 50 children with a diagnosis of gastrointestinal polyps
      managed at Mackay Memorial Hospital between January 1984 and April 2007.
      Demographic data; clinical features; polyp size, number and location; endoscopic
      findings; management; pathology; and information on recurrences were extracted
      from the clinical records. RESULTS: The distribution of polyps in the 50 patients
      included gastric (4 patients), duodenal (2), ileocecal (4) and colorectal polyps
      (40). All patients with gastric polyps presented with vomiting, and three of the
      four patients with ileocecal polyps presented with intussusception. The mean age
      of the 40 patients with colorectal polyps was 6.8 years. The majority of those
      polyps were in the rectosigmoid colon; 36 patients presented with hematochezia.
      Solitary polyps were identified in 33 patients and multiple polyps were
      identified in seven patients. Most of the colorectal polyps were less than 2cm in
      diameter. Histologically, the most frequent type was juvenile polyp. CONCLUSION:
      Gastrointestinal polyps in children are usually benign. Pediatricians treating a
      child with a gastrointestinal polyp should pay attention to the immediate
      complications of the polyps, such as intussusception or bleeding, the
      extraintestinal manifestations and long-term risk for malignancy.

PMID- 19856863
TI  - Parenteral nutrition-associated cholestasis in premature babies: risk factors and
      predictors.
AB  - BACKGROUND: One of the most common complications in infants under parenteral
      nutrition treatment is parenteral nutrition-associated cholestasis (PNAC). The
      etiology of PNAC is thought to be multifactorial. The aims of this study were to
      evaluate the risk factors for PNAC in our neonatal intensive care unit and
      determine useful predictors. METHODS: This study enrolled premature infants
      (gestational age <36 weeks) who were admitted to our neonatal intensive care unit
      and treated with parenteral nutrition infusion for at least 2 weeks between
      January 2004 and January 2007. Multiple possible risk factors were analyzed by a
      retrospective review study design. PNAC was defined as direct bilirubin greater
      than 1.5 mg/dL during parenteral nutrition. RESULTS: A total of 62 premature
      infants with prolonged course of parenteral nutrition were eligible for this
      study; 11 (17.74%) of the infants developed PNAC. There were significant
      differences in terms of gestational age, birth body weight, duration of
      parenteral nutrition, septic episodes, and average energy intake during the 2nd
      and 3rd weeks of life between infants with cholestasis and those without
      cholestasis. Of these risk factors, the duration of parenteral nutrition was most
      significant after multivariate logistic regression analysis. CONCLUSION: Young
      gestational age, low birth body weight, more sepsis episodes, and long duration
      of parenteral nutrition were significant risk factors for PNAC in our study. Low
      energy intake during the 2nd and 3rd weeks of life is a predictor for PNAC.

PMID- 19856864
TI  - Human umbilical cord blood cells protect against hypothalamic apoptosis and
      systemic inflammation response during heatstroke in rats.
AB  - BACKGROUND: Intravenous administration of human umbilical cord blood cells
      (HUCBC) has been shown to improve heatstroke by reducing arterial hypotension as
      well as cerebral ischemia and damage in a rat model. To extend these findings, we
      assessed both hypothalamic neuronal apoptosis and systemic inflammatory responses
      in the presence of HUCBCs or vehicle medium immediately after initiation of
      heatstroke. METHODS: Anesthetized rats, immediately after the initiation of heat
      stress, were divided into two groups and given either serum-free lymphocyte
      medium (0.3mL per rat, intravenously) or HUCBCs (5 x 10(6) in 0.3 mL serum-free
      lymphocyte medium, intravenously). Another group of rats were exposed to room
      temperature (26 degrees C) and used as normothermic controls. Heatstroke was
      induced by exposing the anesthetized rats to a high ambient temperature of 43
      degrees C for 68 minutes. RESULTS: After the onset of heatstroke, animals treated
      with serum-free lymphocyte medium displayed hyperthermia, hypotension,
      bradycardia, hypothalamic neuronal apoptosis and degeneration, and up-regulation
      of systemic inflammatory response molecules including serum tumor necrosis factor
      alpha, soluble intercellular adhesion molecule-1 and E-selectin. Heatstroke
      induced hypotension, bradycardia, hypothalamic neuronal apoptosis and
      degeneration, and increased systemic inflammatory response molecules were
      significantly inhibited by HUCBC treatment. Although heatstroke-induced
      hyperthermia was not affected by HUCBC treatment, the serum levels of the anti
      inflammatory cytokine interleukin-10 were significantly increased by HUCBC
      therapy during hyperthermia. CONCLUSIONS: These findings suggest that HUCBC
      transplantation may prevent the occurrence of heatstroke by reducing hypothalamic
      neuronal damage and the systemic inflammatory responses.

PMID- 19856865
TI  - Subclinical histologic chorioamnionitis and related clinical and laboratory
      parameters in preterm deliveries.
AB  - BACKGROUND: Histologic chorioamnionitis (HCA) is associated with preterm delivery
      and with neonatal morbidity and mortality. Because HCA is usually subclinical,
      histologic examination of the placenta is essential for confirmatory diagnosis.
      In the present study, the correlations between subclinical HCA and relevant
      clinical and laboratory parameters were analyzed. METHODS: This was a
      retrospective study. We reviewed the placental histopathologic findings and the
      charts of patients who were admitted to our neonatal intensive care unit after
      delivery and their mothers between January 2007 and March 2008. A total of 77
      preterm infants [gastational age (GA): 32.2 3.4 weeks, birth weight (BW): 1718 +/
      554 g] were categorized as group A with histologic evidence of placental
      inflammation (n=27) or group B without histologic evidence of placental
      inflammation (n=50). Placental histology was studied to identify the presence of
      inflammatory states such as chorioamnionitis, funisitis and deciduitis.
      Laboratory parameters including complete blood count, differential count, and C
      reactive protein (CRP) level of mothers and initial arterial blood gas, glucose
      Level and mean blood pressure of the infants were documented. Gestational age,
      Apgar score, history of prolonged premature rupture of membrane (prolonged PROM),
      gestational diabetes mellitus, meconium-stained amniotic fluid, pregnancy-induced
      hypertension and signs of pre-eclampsia were also collected as clinical
      parameters. All data were analyzed using independent t tests and Fisher's exact
      test, as appropriate. RESULTS: Group A newborns had a significantly lower
      gestational age (30.8 +/- 4.1 weeks vs. 33.0 +/- 2.6 weeks, p < 0.05) and higher
      CRP level (0.56 +/- 0.92 mg/dL vs. 0.12 +/- 0.14 mg/dL, p < 0.05), together with
      higher maternal WBC count (13,002 +/- 4344/microL vs. 10,850 +/- 3722/microL, p <
      0.05) and higher rate of prolonged PROM [14/27 (51.85%) vs. 8/37 (21.62%), p <
      0.05] compared with group B newborns. CONCLUSION: We found that HCA was
      significantly correlated with lower gestational age, higher CRP level of preterm
      infants, higher maternal WBC count, and a higher rate of prolonged PROM. Our
      results demonstrate a significant association between HCA with an elevated CRP
      level in preterm infants. These findings further confirmed the association
      between maternal inflammation and preterm deliveries.

PMID- 19856866
TI  - Sleep quality and immune mediators in asthmatic children.
AB  - BACKGROUND: Asthmatic children have been reported to complain about poor sleep
      quality. Recent research has demonstrated a relationship between sleep and
      circulating cytokines. This study aimed to assess the relationship between serum
      cytokine levels and sleep quality in asthmatic children. METHODS: After an
      initial screening phase at allergy clinic visits, 90 asthmatic children aged 6-12
      years were enrolled to complete the Chinese version of the (Childhood) Asthma
      Control Test (ACT). A questionnaire assessing sleep quality of asthmatic children
      was also administered to all subjects and parents. We determined the serum levels
      of interleukin (IL)-4, IL-6, IL-10, IL-12, total immunoglobulin (Ig) E, and
      protactin at enrollment. RESULTS: Subjects with an ACT score > or =20 were
      assigned to the well-controlled group and those with a score of 19 were assigned
      to the inadequately controlled group. In the well-controlled group, good sleepers
      had a significantly tower mean level of IL-10 and a higher mean ratio of IL-12/IL
      10 compared with the poor sleepers. Furthermore, the serum prolactin level was
      significantly greater in the good sleeper subgroup. In both subgroups, the
      concentrations of IL-6, IL-12 and total IgE were not significant different.
      CONCLUSION: Good sleep is associated with a lower IL-10 level, a higher prolactin
      concentration, and a higher IL-12/IL-10 ratio. Prolactin may have a potential
      role in this immunity shift. Thus, further insight into the functional role of
      cytokines on the sleep quality of asthma sufferers will result in the
      identification of novel therapeutic perspectives.

PMID- 19856867
TI  - X-linked liver glycogenosis in a Taiwanese family: transmission from undiagnosed
      males.
AB  - X-linked liver glycogenosis (XLG), also known as glycogen storage disease type
      lXa, is characterized by hepatomegaly, abnormal liver functions and growth
      retardation. It is caused by mutations in the PHKA2 gene that encodes the alpha
      subunit of phosphorylase kinase (PHK). XLG can be divided into two subtypes: XLG
      I, with a deficiency in PHK activity in peripheral blood cells and the liver; and
      XLG-II, with normal PHK activity in vitro. This report describes two boys who
      presented with hepatomegaly and abnormal liver function. Pedigree analysis
      revealed them to be fifth-degree relatives, with the disease transmitted through
      undiagnosed grandfathers. Liver histology confirmed GSD diagnosis, and both cases
      had a deficiency in PHK activity in red blood cells and liver tissues. This is
      the first report of XLG-I in the ethnic-Chinese population in Taiwan. This report
      indicates that XLG may be undiagnosed or underestimated. A correct diagnosis is
      necessary for proper management and genetic counseling.

PMID- 19856868
TI  - Pfeiffer-like syndrome with holoprosencephaly: a newborn with maternal smoking
      and alcohol exposure.
AB  - We report the case of a female infant with Pfeiffer-like syndrome and
      holoprosencephaly. She had a cloverleaf skull, ocular proptosis, broad thumbs and
      halluces, and variable accompanying anomalies compatible with Pfeiffer syndrome.
      She also displayed microcephaly, short palpebral fissures, and a smooth philtrum,
      which are clinical signs consistent with fetal alcohol syndrome. She suffered
      from multiple congenital anomalies and died at 41 days of age. Cardio-pulmonary
      failure, brain abnormalities, prematurity, and multiple complications contributed
      to her death. The patient displayed normal chromosomal numbers and type. DNA
      analysis did not reveal fibrobtast growth factor receptor (FGFR) genes FGFR1,
      FGFR2, FGFR3 or TWIST gene mutations. We review the previous reports of Pfeiffer
      syndrome and holoprosencephaly and describe our infant patient with Pfeiffer-like
      syndrome, holoprosencephaly, and heavy in utero maternal alcohol and smoking
      exposures.

PMID- 19856869
TI  - Early development of acute myeloid leukemia following treatment of osteosarcoma:
      a case report and review of the literature.
AB  - We report a case of treatment-related acute myeloid leukemia (t-AML) in a 16-year
      old male following treatment for osteosarcoma (OS). He had been treated with a
      protocol comprising neoadjuvant chemotherapy, definitive surgery with wide
      excision and adjuvant chemotherapy for OS. Four months after completion of the
      treatment, a routine hemogram showed hyperleukocytosis with 90% blasts. Bone
      marrow aspirate and a chromosomal analysis disclosed acute myeloid leukemia
      (AML), M5b with 46, XY, t(11;19)(q23;p13.3). The t-AML was characterized by early
      development (just 4 months after completion of chemotherapy for OS) and
      generalized leukemia cutis. The patient received an alkylating agent (ifosfamide)
      and DNA topoisomerase II-targeted drugs (etoposide and doxorubicin). In terms of
      latency, cytogenetics, and presentation, DNA topoisomerase II-targeted drug
      related leukemia seemed likely for this patient. Clinically, his leukemia cutis
      had developed during a nadir in white blood cell count after the first induction
      of chemotherapy for AML. The rapid progression and its refractoriness to
      chemotherapy were poor prognostic signs.

PMID- 19856870
TI  - [Thromboelastometry--a new method supporting the therapeutical decisions in the
      coagulopathy based on the Hartet's thromboelastography].
AB  - Thromboelastometry is a diagnostic method presenting in graphs and numbers the
      dynamics of hemostasis and physical properties of the clot forming.
      Thromboelastometry allows quick and complete assessment of clotting and
      fibrinolysis mechanism respecting share of coagulation and fibrinolytic factors
      and also platelets. Interpretation is based on comparative analysis of model data
      from computer memory with graphs and numeric data that present clot formation and
      fibrinolysis in time periods. Graphic presentation of quality and dynamics of
      coagulation process allow to understand its disorders caused for different
      reasons, like coagulation factors deficiency, thrombocytopenia, massive bleeding
      and transfusion or sometimes hypothermia. Measuring device used for
      thromboelastometry is mobile and makes possible to test blood by a patient bed.
      By introducing specialist reagents that activate clotting in vitro it is possible
      to shorten the diagnostic period to 15 minutes therefore multiple patient
      hemostasis controls can be achieved in real time. Quick diagnostic and
      possibility of assessment an influence of applied treatment on coagulation
      process allow to make proper therapeutic decisions in patients with coagulopathy.
      Hemostasis image and reference to clinical situation might be helpful in
      diagnosis if there is a surgical bleeding or there is a bleeding released by
      coagulation and fibrinolytic disorders. Thromboelastometry contributes not only
      to widen knowledge about complex mechanics of coagulation disorders but also to
      reduce usage of blood and its products. Thromboelastograhic examinations play a
      major role in the documentation of coagulation disorders treatment. In order to
      widen use of this method in clinical practice the algorithms are created, based
      on thromboelastometry and thromboelatograhy results. These can indicate type and
      quantity of blood products and medicines that are necessary to administer.
      Thromboelastometry is applied in many medical disciplines like cardiothoracic
      surgery, transplant surgery, obstetrics, multiorgan failures, vascular surgery
      and intensive care. In this method specialistic laboratory education is
      unnecessary.

PMID- 19856871
TI  - [Prevalence and difficulties in chronic obstructive pulmonary disease diagnosis
      in patients suffering from severe peripheral arterial disease].
AB  - Cigarette smoking is the most prominent risk factor for chronic obstructive
      pulmonary disease (COPD) and peripheral arterial disease (PAD). Prevalence of
      COPD among cigarette smokers is about 23% in Poland. Effort dyspnea which
      develops in advanced stage of COPD is the leading cause of seeking medical
      advice. Physical activity among patients with PAD is reduced due to intermittent
      claudication. It may cause delayed COPD diagnosis in this group of patients. THE
      AIM OF THE STUDY: To estimate the prevalence of COPD among patients suffering
      from severe PAD who were hospitalized in surgery department due to critical limb
      ischemia and to evaluate difficulties during COPD diagnosis in this group of
      patients. MATERIAL AND METHODS: We examined 64 patients suffering from severe PAD
      (at least IIb stage according to Fontaine's scale). Patients were asked about the
      typical symptoms of COPD: chronic cough, regular sputum production and dyspnea.
      To evaluate the intensity of dyspnea we used British Medical Research Council
      scale. Spirometry was performed to every patient. Patients with airways
      obstruction underwent spirometry after the administration of inhaled
      bronchodilator. Every patient who had the post-bronchodilator value of FEV,/FVC
      ratio below the lower limit of normal values was diagnosed with COPD. RESULTS: It
      was not possible to evaluate the dyspnea intensity using MRC scale in 44% of 34
      patients who reported dyspnea. During the study we diagnosed 16 patients with
      COPD (9 pts had 1st stage of COPD according to GOLD classification, 7 pts--2nd).
      9 patients had been formerly diagnosed with COPD (2 pts--1st stage, 5 pts--2nd,
      and 2 pts--3rd). Spirometry-defined COPD was present in 39% of study group. The
      analysis of data from patients with PAD coexistent COPD revealed that 60% of them
      were current cigarette smokers and 28% of them declared passive smoking exposure.
      The other known negative prognostic factors in patients with COPD such as BMI
      lower than 21 kg/mr2, FEV1% of predicted value below 65% and X-rays photograph
      visible emphysema were observed in 40%, 32% and 12% of patients with PAD and
      coexistent COPD respectively. Hypertension was present in 52% of patients with
      PAD and coexistent COPD, cardiac arterial disease in 52% and chronic heart
      failure due to cardiac arterial disease in 36%. Further analysis of laboratory
      tests revealed dyslipidemia and chronic kidney disease in 52% and 60% of these
      patients respectively. CONCLUSIONS: COPD diagnosis among patients suffering from
      severe PAD involves several difficulties such as uselessness of MRC dyspnea scale
      and frequent heart diseases which delay the COPD diagnosis being considered as
      primary dyspnea reason. Many factors which have been proven to be responsible for
      worse prognosis due to COPD were observed in patients with PAD and coexistent
      COPD. High prevalence of COPD among patients suffering from PAD suggests the
      spirometry as a COPD screening would be justified in that group.

PMID- 19856872
TI  - [Influence of complex compounds on the activity of antioxidant enzymes in
      neoplastic diseases of the digestive tract].
AB  - Chemotherapy is an important field of clinical medicine and pharmacology
      Chemotherapy is the main method of treating the neoplasm. It involves treating
      the neoplastic disease with the use of natural or synthetic anticancer drugs
      commonly known as the cytostatics. The cancer therapy involving the cytostatics
      is a difficult and not always effective process, which requires taking into
      consideration the mechanisms of action, pharmacokinetics and the dosage schemas.
      The complexity of the chemotherapy is influenced by: still incomplete knowledge
      of causes of neoplasm formation, slight biological differences between the cancer
      cells and the regular cells, very small selectivity of cytostatics' action,
      narrow therapeutic index of the anticancer drugs, high toxicity for healthy cells
      and unsatisfactory anticancer activity. The aim of the study was to obtain the
      complex compounds of copper (II), and especially of dinitrate (V) di (3,4, 5
      trimethyl-N1-pyrazol-kappaN2) copper (II), and its subsequent testing for pro-
      and antioxidative activity in people suffering from neoplastic diseases of the
      digestive tract (colorectal and gastric carcinoma). Material and methods. The
      activity of catalase was determined in erythrocytes patients suffering from
      colorectal and gastric carcinoma and in control group (hernia, chronic gastric
      ulcer disease and haemorrhoids) using the method of Beers and Sizer at 240 nm on
      the Beckman spectrophotometer. RESULTS: The results of the test on catalase in
      patients suffering from colorectal and gastric carcinoma indicate that the
      addition to the blood of the complex compound of Cu(II) significantly influences
      the activity of the enzyme in comparison with the control group in which the
      substance tested was not used. In the tests a marked statistical difference was
      observed between the studied and the control group. CONCLUSION: The results
      reveal that chemical compounds, that is, dinitrate (V) di (3,4,5-trimethyl-N1
      pyrazol-kappaN2) copper (II), has a significant influence on the activity of
      catalase, the antioxidant enzyme.

PMID- 19856873
TI  - [The effect of chronic alcohol drinking on the total concentration of sialic acid
      and lipid-bound sialic acid].
AB  - Chronic alcohol drinking markedly influence on the total level of sialic acid
      (TSA) and glycolipids in the blood. The diagnostics parameter that connects the
      evaluation of these both metabolites is sialic acid attached to glycolipids named
      lipid-bound sialic acid (LSA). THE AIM OF THE STUDY: To evaluate an effect of
      chronic alcohol consumption on the serum level of TSA and LSA taking into
      consideration the presence of hepatocellular injury proved by liver enzymes
      activity. Additionally, the diagnostic usefulness of serum TSA and LSA
      determination was compared with traditional markers of alcohol abuse and
      hepatocellular injury. MATERIAL AND METHODS: The experimental group comprised 118
      alcohol-dependent subjects. They were divided into 2 subgroups according to the
      liver enzymes activity. The diagnosis of dependency was made on the basis of ICD
      10 criteria. The control group was consisted of 27 healthy social drinkers. LSA
      was measured according to the resorcinol method described by Katopodis and Stock,
      and TSA was assayed with a colorimetric enzymatic method. RESULTS: The TSA and
      LSA concentrations in the alcohol abuse patients were significantly higher than
      that of healthy controls. Taking into consideration the presence of
      hepatocellular injury, the concentration of LSA differs between subgroups with
      elevated and normal liver enzymes activity but the levels of TSA does not differ.
      The elevated level of LSA distinguish (ROC analysis) the patients with normal and
      elevated liver enzymes activity but the level of TSA does not. Diagnostic power
      of TSA and LSA determination in the sera of alcohol dependent patients was lower
      than that of AST and GGT. CONCLUSION: From this study we can conclude that TSA
      can be recognized to be a good test of alcohol abuse independent on the presence
      of hepatocellular injury but LSA indicated on the alcoholic hepatocellular
      injury.

PMID- 19856874
TI  - [Hearing assessment of children treated with Cisplatin].
AB  - THE AIM OF THE STUDY: Cisplatin's effect on the inner ear in children and compare
      results of the tonal audiometry and the oto-acousitic emission audiometry.
      MATERIAL AND METHODS: Audiological examinations were conducted on 33 children who
      had been treated with Cisplatin. Normal hearing prior to the cytostatic therapy
      would qualify a child for inclusion in the examinations. Cisplatin was
      administered via intravenous infusion in dosages of 15 mg/m2 to 20 mg/m2 on five
      successive days of each month or 50-75 mg/m2 every 3 weeks. The patients were
      divided into groups according to ratio of the cumulative dosage per 1 m2 of the
      body area. Hearing was assessed with tonal and impendence audiometry as well as
      oto-acousitic emission audiometry--DPOAE. RESULTS: The tonal audiometry helped
      detect hearing damage in 12 out of the 33 children participating in the
      examination, with unilateral loss found in 2 and bilateral loss encountered in 10
      children. Hearing threshold shifts ranged between 10 and 40 dB in frequencies
      above 2000 Hz. The largest hearing threshold shift was registered for the region
      of 6000-8000 Hz. Tonal audiometry and oto-acoustic emission audiometry result
      consistency was encountered in 11 children from the study group. CONCLUSIONS: No
      effect of the cytostatic dose level on the degree of hearing loss could be
      demonstrated in the examined group of children. The sensitivity of the oto
      acoustic emission and of the tonal audiometry to detect and monitor hypacusis
      were found to be comparable.

PMID- 19856875
TI  - [Factors determining admission to psychiatric hospital in mentally retarded
      patients].
AB  - The aim of environmental model of psychiatric care, which is nowadays functioning
      in developed countries, is not only improve the quality of life of people with
      psychiatric disorders, among which there are mentally retarded patients, but also
      decrease the number and duration of psychiatric hospitalization. Mentally
      retarded patients have basically weaker adjustment abilities to changing
      conditions of the daylife routines, as well as they are more susceptible to
      psychiatric disorders than general population. Taking that into consideration it
      seems interesting to investigate the reasons of psychiatric hospitalization. THE
      AIM OF THE STUDY: To investigate the reason of psychiatric hospitalization among
      mentally retarded patients. MATERIAL AND METHODS: The medical documentation of
      patients hospitalized in Babiriski's Hospital in Lodz (SPZOZ im.Babinskiego) in
      2006 with diagnosis of mental retardation (F70-F79 according to ICD-10). The
      patients hospitalized throughout the year 2006 with comorbid psychiatric
      diagnosis as well as those with only stated mental retardation were taken into
      account. The analysis was based on questionnaire specially prepared for that
      paper. The results were statistically analyzed. CONCLUSIONS: Analysis of results
      allowed to form the following conclusions: (1) The most frequent indirect reasons
      of psychiatric hospitalization were: aggression, appearance or worsening of
      psychotic symptoms, worsening or change of behavior. Directly hospitalizations
      were determined by environmental reasons among which conflicting relationships
      and lack of personal support were the most common. (2) Behavior and impulse
      disorders were the most frequently observed among men, psychotic disorders among
      women. Psychotic decompensations were the most frequent at mentally retarded in
      light degree, behavior disorders among severe mentally retarded. 3) The
      occurrence of psychiatric disorders which determine psychiatric hospitalization
      is mainly the consequence of adverse environment factors and difficulties in
      adjustment to them.

PMID- 19856876
TI  - [Disseminated intravascular coagulation in abdominal aortic aneurysm--case
      report].
AB  - Disseminated intravascular coagulation (DIC) constitutes a rare presentation form
      of aortic aneurysms. In majority of cases, DIC is asymptomatic and has chronic
      course, but in 0.5-4% of patients it is clinically overt. Very seldom DIC leads
      to diagnosis of previously unknown aortic aneurysm. The authors describe a case
      of 84 years old man referred to hospital due to haemorrhagic diathesis with
      laboratory results consistent with overt DIC. A CT scan demonstrated abdominal
      aortic aneurysm (AAA) as an underlying disorder. The patient was treated with
      fresh frozen plasma and enoxoparine. After reaching the clinical and laboratory
      improvement he was proposed with placing an endoluminal stent graft, but he did
      not agree for operation. The multidisciplinary management of this patient is
      presented and some issues concerning the epidemiology, treatment and coagulation
      assessment of AAA patients with DIC are discussed.

PMID- 19856877
TI  - [PET-CT in evaluation of pulmonary nodule--case report].
AB  - A 52-year-old woman underwent a left nephrectomy for clear cell type renal
      carcinoma. One year after, chest computed tomography revealed the presence of
      small nodule (7 mm) in 9th segment of right lung. Radiological examination not
      make possible to determine a character of the nodule. Positron emission
      tomography with computed tomography in patient no demonstrated increased
      fluorodeoxyglucose uptake typical for malignant tumors. Diagnosis of the small
      peripheral nodules in the lung is very difficult. The most important specificity
      and sensitivity to distinguish benign from malignant was described for PET-CT. It
      is first paper in Poland about use of the PET-CT in differential diagnosis small
      nodules in lung.

PMID- 19856878
TI  - [Calcyphylaxis in a patient with end-stage renal disease in the course of
      systemic lupus erythematosus, diagnostic problems--case report].
AB  - Calcyphylaxis consists in vascular calcium deposition and skin necrosis, which
      appears in the final stage of renal failure. Advanced forms of systemic
      connective tissue disease such as lupus erythematosus, especially with
      concomitant vasculitis, leading to renal failure and uremia may be conducive to
      calcyphylaxis. We are presenting a case of a 50-year-old male requiring chronic
      peritoneal dialysis since the age of 43, due to end-stage renal disease resulting
      from chronic glomeluronephritis. The patient presented to our Dermatology
      Department with large and painful coalescent cutaneous lesions on both lower
      extremities, fingertips and lips. Both clinical picture and disease history
      indicated systemic vasculitis that was previously unrecognized. Additional
      examinations revealed the following markers of inflammation: leukocytosis (11
      G/I) with normal level of eosinophils, CRP > 0.6 mg/I, ESR 120 mm/h, and IgG 20
      g/l, without any source of infection. Indirect immunofluorescence showed the
      absence of antineutrophil cytoplasmic antibodies (ANCA) on polynuclear
      leucocytes. A distinct fluorescence pattern observed in liver sinusoids was
      suggestive of the presence of some form of anti-granulocyte antibodies. Anti
      nuclear antibodies (ANA) were detected in serum (1:1000) with homogenous and
      microgranular fluorescence pattern. Anti-extractable nuclear antigen panel (ENA),
      C3/C4 levels, anti-smooth muscle, anti-dsDNA and anti-glomerular basement
      membrane (GBM) antibodies were within normal limits. Lupus band test revealed IgA
      and IgG deposits at the dermis-epidermis junction. Histopathological examination
      of the skin showed calcification complicated by small vessel thrombosis, however,
      it was non-specific for vasculitis. Our case represents an example of
      calcyphylaxis associated with a widespread medial vascular calcification in a
      patient with end stage renal disease secondary to systemic lupus erythematosus.
      Although renal dialysis itself is known to trigger calcyphylaxis, there have been
      few reports in literature suggesting that collagen vascular disease may also
      contribute to this process.

PMID- 19856879
TI  - [Benign acute childhood myositis (BACM)--cases report].
AB  - Benign acute childhood myositis (BACM) is characterised by sudden calf pain and
      inability to walk. We analyzed the characteristics of seven boys and two girls
      with BACM treated in the Pediatric Department from April 2005 to March 2009. The
      mean age at onset of symptoms was 7 +/- 2 years. Two boys were hospitalized twice
      for BACM. All cases occurred in winter or spring. 7 out of all admissions were
      clustered together in one week long periods. Patients demonstrated prodromal
      symptoms of flu-like illness followed by the sudden onset of difficulty in
      walking. One girl additionally complained of a painful right hip. Four patients
      received inosine pranobex for prodromal viral infection before the clinical onset
      of myositis. In all cases, creatine phosphokinase (CPK; the highest value at 8988
      U/l) and aspartate aminotransferase (AST; the highest value at 329 U/l) values
      were elevated. The serum concentration of myoglobin was elevated in five out of
      six tested patients (the highest value at 2172 microg/l). The following
      haematological abnormalities were detected: leucocytopenia (the lowest WBC 1.35 x
      10(3)/microl), neutropenia, and trombocytopenia. All patients made a rapid
      recovery within 1 to 5 days. Pediatricians and emergency medicine specialists
      must be aware that BACM is a self-limiting disorder with the acute onset of
      inability to walk, elevated CPK and AST levels, and transient haematological
      abnormalities. There is no sufficient data from clinical reports on
      immunostimulant use before the onset of BACM.

PMID- 19856880
TI  - [The use of platelet rich plasma in treatment of chronic inflammation of bones].
AB  - Failure of antibiotic therapy in the treatment of inflammation of the skeletal
      system forces the search for alternative and complementary methods. One of these
      methods is the application of platelet-rich substances (PRP). THE AIM OF THE
      STUDY: To present the results of treatment of the ostitis not cured successfully
      in a surgical way and by use of antibiotics. The presented material is based on
      10 case studies of the authors' own patients treated for chronic, inflammation of
      bones by use of PDGF between 2005-2007 in Department of Orthopedics Surgery of
      Hospital of MSWiA with WMCO. The presented results of the use of platelet-rich
      substances encourage to popularize their application as a clinical treatment
      supporting the commonly known methods. Based on the presented clinical analysis
      the use of platelet-rich plasma can be recommended in the treatment of the
      inflammation of bones.

PMID- 19856881
TI  - [Pulmonary hypertension and pulmonary embolism in chronic obstructive pulmonary
      disease].
AB  - Chronic obstructive pulmonary disease (COPD) is a disease associated with high
      increasing worldwide mortality. COPD-related mortality is probably underestimated
      because of difficulties associated with identifying the precise cause of death.
      Respiratory failure is considered the major cause of death in advanced COPD.
      Comorbidities such as cardiovascular diseases (pulmonary hypertension, pulmonary
      embolism, ischemic heart disease, arrhythmia, stroke) are also major causes and
      in COPD, are leading causes of mortality. The links between COPD and these
      conditions are not fully understood. However a link through the inflammation
      pathway has been suggested.

PMID- 19856882
TI  - [HCV entry as a new therapeutic target in chronic hepatitis C].
AB  - According to WHO data the hepatitis C virus (HCV) has already infected 170
      million people worldwide, and 750,000 of them in Poland what amounts some 1.4% of
      general country population. Currently used antiviral therapy with pegylated
      interferon alpha and ribavirin has only 50% effectiveness. Many new drugs and
      molecules, especially inhibiting viral replication, are studied in preclinical
      and clinical trials. However, still unknown HCV entry process can be a new,
      promising therapeutic target in chronic HCV infection.

PMID- 19856883
TI  - [Aquaporins--a new element in the regulation of body water homeostasis].
AB  - Aquaporins represent an ubiquitous class of integral membrane proteins that are
      serving in the passage of water across cell membrane. A subset of aquaporins may
      additionally facilitate transmembrane permeation of small neutral solutes such as
      glicerol (aquaglyceroporins). The widespread occurrence and an unique function of
      aquaporins give rise to the high degree of their intra- and interspecies
      homology, especially in their regions forming the internal wall of channel. The
      review presents current knowledge about the role of water channels in regulation
      of body homeostasis basing on results of experiments with mice lacking various
      aquaporins genes and studies on humans with inherited or acquired abnormalities
      in their function as well as about potential perspectives of pharmacological
      regulation of aquaporin activity.

PMID- 19856884
TI  - [The search for new antitumor medicines].
AB  - Tumor illnesses belong to the major problems of contemporary medicine. A crucial
      group of medicines used in the antitumor therapy are complexes of platinum (II).
      The first medicine introduced into the treatment of various tumors was cis
      platinum. This compound was first used at the beginning of the 1970s. It is used
      up to now in the treatment of ovary, esophagus, testicle and neck tumors. The
      second medicine used in chemotherapy was carboplatin. The medicines mentioned
      above have a similar method of activity but they differ in toxicity. The main
      area of research of contemporary medicine is the constant search for new
      antitumor medicines which would be characterized by a better therapeutic index in
      comparison with cis-platinum.

PMID- 19856885
TI  - [Therapeutic intervention in diseases with advanced glycation end products in
      their pathogenesis].
AB  - Nonenzymatic modification of proteins by reducing sugars, a process that is also
      known as the Maillard reaction, leads to the formation of advanced glycation end
      products (advanced glycation end-products--AGEs) in vivo. There is a growing body
      of evidence that formation and accumulation of AGEs progress during normal aging,
      and at an extremely accelerated rate under diabetes, and are thus involved in the
      pathogenesis of various diseases such as diabetic vascular complications,
      neurodegenerative diseases, renal failure, and liver cirrhosis. Therefore,
      inhibition of AGEs formation may be a promising target for therapeutic
      intervention in AGEs-related disorders. There is a growing body of evidence that
      AGEs and their receptor (receptor for advanced glycation endproducts--RAGE) axis
      are also implicated in the pathogenesis of various diseases. In the former part
      of this paper, we discuss several types of AGEs inhibitors and their therapeutic
      implications in diseases. Then we summarize in the latter part of this review
      recent findings regarding pathophysiological roles in diseases of RAGE and
      soluble RAGE and discuss their potential usefulness as therapeutic targets.

PMID- 19856886
TI  - [Influence of genetic factors on development and severity of rheumatoid arthritis
      -part I].
AB  - Both genetic and environmental factors affect susceptibility, severity and
      probably drugs' efficacy in patients with rheumatoid arthritis (RA). After
      initial completion of the Human Genome Project on the 16th February 2001,
      significant progress has been made in identifying other than HLA genome regions
      linked to the increased RA susceptibility. As an effect several new genes have
      been recognized as an HLA-independent genetic risk factors of RA. PTPN22 gene
      polymorphism, C5/TRAF1 genes region polymorphism and TNFAIP3-OLIG3 genes region
      polymorphism(s) are among newly identified and already confirmed genetic risk
      factors, whereas STAT 4, CTLA4, PADI4 and IRF5 genes polymorphisms are listed
      among probable RA development genetic risk factors.

PMID- 19856887
TI  - [Influence of genetic factors on development and severity of rheumatoid arthritis
      -part II].
AB  - In our previous paper we have presented recent advances in the knowledge of the
      genetic risk factors predisposing to rheumatoid arthritis development. In
      contrast to the progress that has been made in identification of genes
      responsible for susceptibility to RA, there is still little known about genetic
      risk factors of the more aggressive and (or) refractory RA. In this part of our
      review we present a detailed knowledge of the role of genetic factors in severity
      of RA. Gene polymorphisms of the TNF-alpha gene (-238G/A, -308G/A, +489G/ A), IL
      1beta gene (-11C/T, +3953C/T), IL-4 gene (-590C/T), MMP genes (-1607 ins1G/del2G,
      -1612 ins/del A) and TRAF1/C5 genes region (rs 10818488) are among the most
      intensively investigated HLA independent genetic risk factors of the severe
      course of RA.

PMID- 19856888
TI  - [Clinical significance of some genetic polymorphisms of cytochrome P-450
      subfamilies CYP2D, CYP2E and CYP3A--part II].
AB  - 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- 19856889
TI  - [Depression in Parkinson's disease].
AB  - Parkinson's disease (PD) belongs to degenerative diseases of brain in which,
      apart from many somatic symptoms, there also occur depressive disorders of mental
      sphere. This paper presents possible reasons for the development of depression in
      PD: psychological resulting from the presence and the development of chronic
      disease as well as neurochemical disorders that reveal in this background. It has
      been highlighted that the presence of PD has a significant effect on the
      patients' life quality The paper discusses possible important factors for the
      progress of depression syndromes: decrease in everyday life activities, somatic
      state heaviness, worsening of motor functions, cognitive deficits. The possible
      occurrence of typical depression syndrome manifested in PD, its modifications and
      possible axial symptoms were analyzed. Two modifications of depression syndrome
      were also described. The results of the study on the increased lethality in
      patients with PD were presented. Special attention was paid to the occurrence of
      apathy with no key signs of depression syndrome. The existence of relations
      linking the apathy with cognitive disorders were highlighted. The paper discusses
      the occurrence of factors that may affect the revealing of apathy, as well as the
      presence of possible brain dysfunctions in patients.

PMID- 19856890
TI  - [Will Polish investigators have access to the research ethics committees?].
AB  - Polish research ethics committees (REC) provide opinions on projects of medical
      research (A), object to participation of regional investigator or center in
      multicenter clinical trials (B) and provide opinions about amended protocols or
      documentation of investigated medicinal product, which might change safety of
      trials' participants (C). Model of self-financing of REC is in force in Poland.
      Charges collected for opinions should cover incurred costs of REC. Legitimacy of
      collection of charges for proceedings B and C is questioned due to the dimness of
      Polish provisions. At the same time the number of submitted to REC projects of
      medical research decreases but the number of proceedings B and C increases. REC
      should have and office and secretary. The duty to provide opinions B and C and
      lack of A proceedings might cause financial collapse of REC. Shortage of assets
      might deprive investigators of an access to REC. Provisions regulating financing
      model of Polish REC should be amended.

PMID- 19856891
TI  - Alternative dispute resolution and long-term care: can the elderly negotiate a
      fair ADR clause?

PMID- 19856892
TI  - Metathesis of alkanes and related reactions.
AB  - The transformation of alkanes remains a difficult challenge because of the
      relative inertness of the C-H and C-C bonds. The rewards for asserting synthetic
      control over unfunctionalized, saturated hydrocarbons are considerable, however,
      because converting short alkanes into longer chain analogues is usually a value
      adding process. Alkane metathesis is a novel catalytic and direct transformation
      of two molecules of a given alkane into its lower and higher homologues;
      moreover, the process proceeds at relatively low temperature (ambient conditions
      or higher). It was discovered through the use of a silica-supported tantalum
      hydride, ([triple bond]SiO)(2)TaH, a multifunctional catalyst with a single site
      of action. This reaction completes the story of the metathesis reactions
      discovered over the past 40 years: olefin metathesis, alkyne metathesis, and ene
      yne cyclizations. In this Account, we examine the fundamental mechanistic aspects
      of alkane metathesis as well as the novel reactions that have been derived from
      its study. The silica-supported tantalum hydride catalyst was developed as the
      result of systematic and meticulous studies of the interaction between oxide
      supports and organometallic complexes, a field of study denoted surface
      organometallic chemistry (SOMC). A careful examination of this surface-supported
      tantalum hydride led to the later discovery of alumina-supported tungsten
      hydride, W(H)(3)/Al(2)O(3), which proved to be an even better catalyst for alkane
      metathesis. Supported tantalum and tungsten hydrides are highly unsaturated,
      electron-deficient species that are very reactive toward the C-H and C-C bonds of
      alkanes. They show a great versatility in various other reactions, such as cross
      metathesis between methane and alkanes, cross-metathesis between toluene and
      ethane, or even methane nonoxidative coupling. Moreover, tungsten hydride
      exhibits a specific ability in the transformation of isobutane into 2,3
      dimethylbutane as well as in the metathesis of olefins or the selective
      transformation of ethylene into propylene. Alkane metathesis represents a
      powerful tool for making progress in a variety of areas, perhaps most notably in
      the petroleum and petrochemical fields. Modern civilization is currently
      confronting a host of problems that relate to energy production and its effects
      on the environment, and judicious application of alkane metathesis to the
      processing of fuels such as crude oil and natural gas may well afford solutions
      to these difficulties.

PMID- 19856893
TI  - Polynuclear complexes: two amino-phenol macrocycles spaced by several linear
      polyamines; synthesis, binding properties, and crystal structure.
AB  - The synthesis and characterization of the new polytopic ligands 1,14-bis(3,6,9
      triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,6,9,12
      tetraazatetradecane L1, 1,15-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca
      11,13,1(15)-trien-6-yl)-3,6,10,13-tetraazapentadecane L2, and 1,16-bis(3,6,9
      triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,7,10,14
      tetraazahexadecane L3, containing two equal amino-phenol macrocycles spaced by
      several linear tetraamines, are reported. The basicity and coordination behavior
      toward the Cu(II) ion were potentiometrically determined in aqueous solution at
      298.1 K. All the ligands show similar acid-base properties behaving as octaprotic
      bases in the examined pH range (pH = 2-12). The acid protons of L1-L3 cannot be
      removed under the experimental conditions used; thus, the main deprotonated
      species obtainable in aqueous solution are the neutral ligands, having amphionic
      character as demonstrated by UV-vis experiments. These species are able to form
      mono-, di-, and trinuclear Cu(II) complexes having stoichiometry [CuL](2+),
      [Cu(2)L](4+), and [Cu(3)L](6+), respectively, that can lose one or two protons
      giving rise to [CuH(-1)L](+), [Cu(2)H(-2)L](2+), and [Cu(3)H(-2)L](4+). Depending
      on the used ligand to metal molar ratio, the mono-, di-, or trinuclear species
      prevail over the others in solution. Both di- and trinuclear complexes are able
      to add secondary ligands (such as OH(-)), and in some cases two Cu(II) can
      cooperate to stabilize them by coordinating the guest in a bridged conformation.
      The structure of the [Cu(2)L3](4+) cation was resolved by X-ray analysis of the
      {[Cu(2)L3](ClO(4))(4) x 3 H(2)O}(2) x H(2)O crystalline complex. It shows that
      each Cu(II) is penta-coordinated by one phenolate oxygen, two amine functions,
      belonging to one macrocyclic unit, and two amine functions of the spacer; in this
      species the distance between the two Cu(II) is about 5.3 A.

PMID- 19856894
TI  - Kinetic control of intralayer cobalt coordination in layered hydroxides: Co(1
      0.5x)(oct) Co(x)(tet) (OH)2 (Cl)x (H2O)n.
AB  - We report the synthesis and characterization of new structural variants of the
      isotypic compound with the generic chemical formula, Co(1-0.5x)(oct) Co(x)(tet)
      (OH)2 (Cl)x (H2O)n, all modifications of an alpha-Co(OH)2 lattice. We show that
      the occupancy of tetrahedrally coordinated cobalt sites and associated chloride
      ligands, x, is modulated by the rate of formation of the respective layered
      hydroxide salts from kinetically controlled aqueous hydrolysis at an air-water
      interface. This new level of structural control is uniquely enabled by the slow
      diffusion of a hydrolytic catalyst, a simple technique. Independent structural
      characterizations of the compounds separately describe various attributes of the
      materials on different length scales, revealing details hidden by the disordered
      average structures. The precise control over the population of distinct
      octahedrally and tetrahedrally coordinated cobalt ions in the lattice provides a
      gentle, generic method for modulating the coordination geometry of cobalt in the
      material without disturbing the lattice or using additional reagents. A mechanism
      is proposed to reconcile the observation of the kinetic control of the structure
      with competing interactions during the initial stages of hydrolysis and
      condensation.

PMID- 19856895
TI  - Reactions of Pd(II) with chelate-tethered 2,6-diaminopurine derivatives: N3
      coordination and reaction of the purine system.
AB  - Alkyldiamine-tethered derivatives of 2,6-diaminopurine, ethylenediamine-N9-propyl
      2,6-diaminopurine, L1, and ethylenediamine-N9-ethyl-2,6-diaminopurine, L2, react
      with Pd(II) to give N3-coordinated complexes. However, the exact nature of the
      resulting complex is dependent on the reaction conditions. With PdCl(2)(MeCN)(2)
      in MeCN/H(2)O the expected [PdCl(N3-2,6-DAP-alkyl-en)](+) complex, 1, is formed
      with L1 chelating the metal center in a tridentate manner through the diamine
      function and N3 of the purine base. However, under the same conditions the
      shorter, ethyl-tethered, L2 gives a complex dication, 2, containing a
      tetradentate ligand forming simultaneously 5-, 6-, and 7-membered chelate rings.
      This resulting acetamidine, derived by addition to coordinated MeCN, appears to
      be the first such case involving the 2-amino group of a purine. The ethyl
      analogue of 1, [PdCl(N3-2,6-DAP-Et-en)](+) 3, was prepared by reaction of L2 with
      K(2)PdCl(4) in aqueous media.

PMID- 19856896
TI  - Topological dependence of the magnetic exchange coupling in arylethynyl-bridged
      organometallic diradicals containing [(eta(2)-dppe)(eta(5)-C(5)Me(5))Fe(III)](+)
      fragments.
AB  - We have investigated the spin distribution and determined the magnetic exchange
      coupling J(ab) (defined according to the following Hamiltonian: H(spin) = 
      2J(ab)S(a).S(b)) for three arylethynyl-bridged organoiron(III) diradicals
      containing [(eta(2)-dppe)(eta(5)-C(5)Me(5))Fe(III)](+) fragments. Considering the
      distance separating the Fe(III) centers (>or=11 A), remarkably large
      intramolecular magnetic interactions between unpaired spins were found for two of
      them. Thus, an antiferromagnetic coupling (J(ab)) of ca. -190 cm(-1) was
      experimentally determined for the binuclear Fe(III) species featuring a 1,4
      diethynylbenzene bridge 1[PF(6)](2), while a ferromagnetic interaction of over
      +150 cm(-1) was evidenced for its 1,3-substitued analogue 2[PF(6)](2). We also
      show that a much weaker interaction (0 > J(ab) >or= -1 cm(-1)) takes place in the
      4,4'-biphenyl analogue of 1[PF(6)](2) (3[PF(6)](2)), evidencing that insertion of
      an additional 1,4-phenylene unit in the bridge severely disrupts the magnetic
      communication in these diradicals. With the help of NMR and density functional
      theory, the magnetic properties of these compounds were rationalized and compared
      to those of the corresponding mononuclear Fe(III) relatives 4[PF(6)] and
      5[PF(6)]. Finally, it is shown that, for all of these dinuclear Fe(III)
      complexes, the structural changes between singlet and triplet spin isomers remain
      very small regarding the carbon-rich bridge. Thus, even for a strongly coupled
      diradical such as 1[PF(6)](2), a dominant diradicaloid character dominates the
      valence-bond description of the singlet state unpaired electrons.

PMID- 19856897
TI  - Hydrogen-bond directed cyanide-bridged molecular magnets derived from
      polycyanidemetalates and Schiff base manganese(III) compounds: synthesis,
      structures, and magnetic properties.
AB  - A series of six new cyanide-bridged heterometallic complexes including two
      tetranuclear T-like Fe(III)Mn(III)(3) compounds,
      {[Mn(L(1))(H(2)O)](3)[Fe(CN)(5)(1-CH(3)im)]}ClO(4) x 1.5 H(2)O (1) and
      {[Mn(L(2))(H(2)O)](3)[Fe(CN)(5)(1-CH(3)im)]}ClO(4) x 3 H(2)O (2); two
      heptanuclear cage-shaped M(III)Mn(III)(6) (M = Fe, Cr) compounds,
      {[Mn(L(2))(H(2)O)](6)[Fe(CN)(6)]}[Fe(CN)(6)] x 6 CH(3)OH (3) and
      {[Mn(L(2))(H(2)O)](6)[Cr(CN)(6)]}[Cr(CN)(6)] x 6 CH(3)OH (4); and two two
      dimensional M-Mn(III) networks, {[H(3)O][Mn(L(1))](2)[Fe(CN)(6)]} x 2 DMF (5) and
      {K[Mn(L(1))](2)[Cr(CN)(6)]} x 1.5 CH(3)CN x CH(3)OH (6) (L(1) = N,N-ethylene
      bis(3-methoxysalicylideneiminate, L(2) = N,N-ethylene-bis(3
      ethoxysalicylideneiminate) have been successfully assembled from three
      polycyanidemetalates containing five or six cyanide groups and two manganese(III)
      building blocks containing bicompartmental Schiff base ligands. The cyanide
      bridged polynuclear complexes are self-complementary through a coordinated aqua
      ligand from one complex and the free O(4) compartment from the neighboring
      complex, giving supramolecular one-dimensional ladders and three-dimensional
      networks for 1 and 2 and for 3 and 4, respectively. Investigation over magnetic
      susceptibilities of the six complexes reveals the overall ferromagnetic
      interactions for complexes 1, 2, 3, and 5 and antiferromagnetic interaction for 4
      and 6. Compounds 1-4 show some characteristics of metamagnet behavior at low
      temperatures due to the relatively strong intermolecular hydrogen-bonding
      interaction. The two complexes with two-dimensional structure exhibit three
      dimensional antiferromagnetic ordering with typical metamagnetic behavior below
      8.4 K for 5 and 11.5 K for 6, respectively. The present result appears to add new
      members to the very few examples of polynuclear clusters exhibiting 3D magnetic
      ordering relying on intermolecular interactions, to the best of our knowledge,
      which will be helpful for providing valuable information for the understanding
      and application of intermolecular hydrogen-bonding interactions in the molecular
      magnetic materials.

PMID- 19856898
TI  - Synthesis of (NH)(m)(NMe)(4-m)-bridged calix[4]pyridines and the effect of NH
      bridge on structure and properties.
AB  - The (NH)(m)(NMe)(4-m)-bridged calix[4]pyridines (m = 1-4) 19-23 were synthesized
      in excellent yields from deprotection of N-allyl groups of (NAllyl)(m)(NMe)(4-m)
      bridged calix[4]pyridine derivatives 8 and 15-18, which were prepared in moderate
      yields by macrocyclic 2+2 and 1+3 coupling reactions between simple diamino- and
      dibromo-substituted fragments. In the solid state, (NH)(m)(NMe)(4-m)-bridged
      calix[4]pyridines adopted different 1,3-alternate conformations due to mainly the
      formation of varied conjugation systems of bridging NH units with their
      neighboring pyridines. In solution, all (NH)(m)(NMe)(4-m)-bridged
      calix[4]pyridines were very fluxional and the rates of interconversion of various
      conformational structures were very rapid relative to the NMR time scale. While
      (NH)(4)-bridged calix[4]pyridine 23 formed the strongest conjugation system,
      (NH)(2)(NMe)(2)-bridged calix[4]pyridine 21 acted as a selective fluorescence
      probe in the recognition of zinc(II) ion in solution with the dramatic
      enhancement of fluorescence intensity.

PMID- 19856899
TI  - Controlling electron transfer through the manipulation of structure and ligand
      based torsional motions: a computational exploration of ruthenium donor-acceptor
      systems using density functional theory.
AB  - Computational studies using density functional theory (DFT) are reported for a
      series of donor-acceptor (DA) transition metal complexes and related excited
      state and electron transfer (ET) photoproduct models. Three hybrid Hartree
      Fock/DFT (HF/DFT) functionals, B3LYP, B3PW91, and PBE1PBE, are employed to
      characterize structural features implicated in the dynamical control of
      productive forward and energy wasting back ET events. Energies and optimized
      geometries are reported for the lowest energy singlet state in [Ru(dmb)(2)(bpy
      phi-MV)](4+) (DA1), [Ru(dmb)(2)(bpy-o-tolyl-MV)](4+) (DA2), [Ru(dmb)(2)(bpy-2,6
      Me(2)-phi-MV)](4+) (DA3), and [Ru(tmb)(2)(bpy-2,6-Me(2)-phi-MV)](4+) (DA3'),
      where dmb is 4,4'-dimethyl-2,2'-bipyridine, tmb is 4,4',5,5'-tetramethyl-2,2'
      bipyridine, MV is methyl viologen, and phi is a phenylene spacer. These indicate
      that the dihedral angle theta(1) between the aryl substituent and the bipyridine
      fragment to which it is bound, systematically increases with the addition of
      steric bulk. Energies, optimized geometries, and unpaired electron spin densities
      are also reported for the lowest energy triplet state of [Ru(dmb)(2)(4-p-tolyl
      2,2'-bipyridine)](2+) (D1*), [Ru(dmb)(2)(4-(2,6-dimethylphenyl)-2,2'
      bipyridine)](2+) (D2*), [Ru(dmb)(2)(4-mesityl-2,2'-bipyridine)](2+) (D3*), and
      [Ru(tmb)(2)(4-mesityl-2,2'-bipyridine)](2+) (D3'*). Each of these serves as a
      model of a reactant excited state in the forward electron-transfer photochemistry
      allowing us to qualify and quantify the role of excited-state intraligand
      electron delocalization in driving substantial geometry changes (especially with
      respect to theta(1)) relative to its respective DA counterpart. Next, energies,
      optimized geometries, and spin densities are reported for the lowest energy
      triplet of each DA species: (3)DA1, (3)DA2, (3)DA3, and (3)DA3'. These are used
      to model the ET photoproduct and they indicate that theta(1) increases following
      ET, thus, verifying switch-like properties. Finally, we report data for geometry
      optimized DA1 and (3)DA1 in a continuum model of room temperature acetonitrile.
      This study shows a complete recovery of theta(1) to its ground state value which
      has implications in efforts to trap electrons in charge-separated states.

PMID- 19856900
TI  - Crown and bowl-shaped clusters of uranyl polyhedra.
AB  - Bowl (U(16)) and crown-shaped clusters (U(20R) and U(24R)) containing 16, 20, and
      24 uranyl peroxide polyhedra self-assemble in alkaline aqueous solution under
      ambient conditions. Structural analyses of crystallized clusters provided details
      of their topologies. Each contains uranyl hexagonal bipyramids in which two cis
      edges are peroxide, with a third edge defined by two OH groups, as well as
      hexagonal bipyramids in which three edges are peroxide. These are the first open
      uranyl peroxide clusters reported, and they join a growing family of complex
      cluster topologies based on uranium that hold promise for nanoscale control of
      chemistry in nuclear energy cycles.

PMID- 19856901
TI  - Angle-resolved photoemission spectra of graphene from first-principles
      calculations.
AB  - Angle-resolved photoemission spectroscopy (ARPES) is a powerful experimental
      technique for directly probing electron dynamics in solids. The energy versus
      momentum dispersion relations and the associated spectral broadenings measured by
      ARPES provide a wealth of information on quantum many-body interaction effects.
      In particular, ARPES allows studies of the Coulomb interaction among electrons
      (electron-electron interactions) and the interaction between electrons and
      lattice vibrations (electron-phonon interactions). Here, we report ab initio
      simulations of the ARPES spectra of graphene including both electron-electron and
      electron-phonon interactions on the same footing. Our calculations reproduce some
      of the key experimental observations related to many-body effects, including the
      indication of a mismatch between the upper and lower halves of the Dirac cone.

PMID- 19856902
TI  - Direct observation of martensitic phase-transformation dynamics in iron by 4D
      single-pulse electron microscopy.
AB  - The in situ martensitic phase transformation of iron, a complex solid-state
      transition involving collective atomic displacement and interface movement, is
      studied in real time by means of four-dimensional (4D) electron microscopy. The
      iron nanofilm specimen is heated at a maximum rate of approximately 10(11) K/s by
      a single heating pulse, and the evolution of the phase transformation from body
      centered cubic to face-centered cubic crystal structure is followed by means of
      single-pulse, selected-area diffraction and real-space imaging. Two distinct
      components are revealed in the evolution of the crystal structure. The first, on
      the nanosecond time scale, is a direct martensitic transformation, which proceeds
      in regions heated into the temperature range of stability of the fcc phase, 1185
      1667 K. The second, on the microsecond time scale, represents an indirect process
      for the hottest central zone of laser heating, where the temperature is initially
      above 1667 K and cooling is the rate-determining step. The mechanism of the
      direct transformation involves two steps, that of (barrier-crossing) nucleation
      on the reported nanosecond time scale, followed by a rapid grain growth typically
      in approximately 100 ps for 10 nm crystallites.

PMID- 19856903
TI  - Aptamer fiber anchored on the edge of a protein pattern: a template for nanowire
      fabrication.
AB  - How to lay down nanowires at designated positions is a challenge that undermines
      the development of nanowire-based devices. We demonstrate that aptamer fibers,
      which are formed by the self-assembly of multiple aptamers, anchor specifically
      on the edge of protein patterns. This edge-anchoring effect originates from the
      biospecific recognition between the aptamer and its target protein. The fractal-
      shaped aptamer fibers are 1-6 nm high and can be tens of micrometers long. Once
      these edge-bound fibers have formed, they can serve as scaffolds for further
      assembly processes. We used these aptamer fibers as templates to fabricate
      palladium and streptavidin nanowires, which anchored on the pattern edges and
      never cross over or collapse over each other. The aptamer fiber scaffold provides
      a solution for fabricating and interfacing nanowires to existing surface
      patterns.

PMID- 19856904
TI  - Enantioselective synthesis of allylic alcohols via an oxazaborolidinium ion
      catalyzed Diels-Alder/Retro-Diels-Alder sequence.
AB  - A triflimide-activated oxazaborolidine catalyst successfully promoted the
      asymmetric Diels-Alder reaction of 9-methylanthracene with methacrolein in high
      regio- and enantioselectivity. The cycloadduct obtained was subsequently used as
      a chiral template to access secondary and tertiary allylic alcohols in good to
      high enantiomeric excess via a cycloreversion by flash vacuum pyrolysis.

PMID- 19856905
TI  - Top-down fabrication of sub-30 nm monocrystalline silicon nanowires using
      conventional microfabrication.
AB  - We report a new low-cost top-down silicon nanowire fabrication technology
      requiring only conventional microfabrication processes including
      microlithography, oxidation, and wet anisotropic plane-dependent etching; high
      quality silicon nanowire arrays can be easily made in any conventional
      microfabrication facility without nanolithography or expensive equipment. Silicon
      nanowires with scalable lateral dimensions ranging from 200 nm down to 10-20 nm
      and lengths up to approximately 100 microm can be precisely formed with near
      perfect monocrystalline cross sections, atomically smooth surfaces, and wafer
      scale yields greater than 90% using a novel size reduction method where silicon
      nanowires can be controllably scaled to any dimension and doping concentration
      independent of large contacting regions from a continuous layer of crystalline
      silicon.

PMID- 19856906
TI  - Mg(OOCCH3)2 interface modification after sensitization to improve performance in
      quasi-solid dye-sensitized solar cells.
AB  - In this paper, a simple yet efficient method is proposed to improve the
      performance of dye-sensitized solar cells (DSCs) by modification after
      sensitization using Mg(OOCCH(3))(2). With modification of Mg(OOCCH(3))(2), a blue
      shift of the absorption peak and optical band gap were observed in the UV-vis
      spectrum. As shown in the Fourier transform infrared spectrum, the intermolecular
      hydrogen bonding of N3 dye, which caused the aggregation of dye molecules, was
      weakened. As shown in the I-V characteristic, the conversion efficiency of the
      DSCs was improved by the treatment of Mg(OOCCH(3))(2). Furthermore, the charge
      recombination was retarded as evidenced by the decreased dark current and the
      slowed decay rate of the dye excited state, which were characterized by the I-V
      curve in dark and transient photovoltage spectra. The mechanism of this
      modification process was also proposed further. Modification with Mg(OOCCH(3))(2)
      facilitated the electron injection from the dye molecule to the conductive band
      of TiO(2) by raising the excited state energy level of the dye molecule. This
      energy level rising was evidenced by the results of the cyclic voltammetry test
      and the blue shift of the optical band gap. Furthermore, Mg(OOCCH(3))(2) worked
      as an insulating barrier layer at the sensitized TiO(2)/electrolyte interface,
      thereby retarding the charge recombination in DSCs.

PMID- 19856907
TI  - Growth velocity and direct length-sorted growth of short single-walled carbon
      nanotubes by a metal-catalyst-free chemical vapor deposition process.
AB  - We report on the observation of a very low growth velocity of single-walled
      carbon nanotubes (SWNTs) and consequently the direct length-sorted growth and
      patterned growth of SWNTs by using a metal-catalyst-free chemical vapor
      deposition (CVD) process proposed recently by our group, in which SiO(2) serves
      as catalyst. We found that the growth velocity of the SWNTs from SiO(2) catalyst
      is only 8.3 nm/s, which is about 300 times slower than that of the commonly used
      iron group catalysts (Co as a counterpart catalyst in this study). Such a slow
      growth velocity renders direct length-sorted growth of SWNTs, especially for
      short SWNTs with hundreds of nanometers in length. By simply adjusting the growth
      duration, SWNTs with average lengths of 149, 342, and 483 nm were selectively
      obtained and SWNTs as short as approximately 20 nm in length can be grown
      directly. Moreover, comparative studies indicate that the SiO(2) catalyst
      possesses a much longer catalytic active time, showing sharp contrast with the
      commonly used Co catalyst which quickly loses its catalytic activity. Taking
      advantage of the very slow growth velocity of the SiO(2) catalyst, patterned
      growth of SWNT networks confined in a narrow region of <5 microm was also
      achieved. The short SWNTs may show intriguing physics owing to their finite
      length effect and are attractive for various practical applications.

PMID- 19856908
TI  - Fundamental link between folding states and functional states of proteins.
AB  - Folding and function of proteins are two aspects of proteins which are usually
      considered as basically unrelated phenomena that are optimized by evolution
      independently. From the funnel model of folding/unfolding and the associated
      energy landscape, we infer the paradigm that the minimum number of folding
      intermediates is determined by the number of all functional states of a protein
      ("essential" folding intermediates). Here, we demonstrate the supposed
      fundamental link using the Ras protein complexed with the GTP analogue GppNHp
      that occurs in two structural states coexisting in solution. State 2 was shown
      earlier to represent the effector interacting state, and the function of state 1
      was hitherto unknown. By (31)P NMR spectroscopy, we demonstrate that state 1
      represents the conformation interacting with guanine nucleotide exchange factors
      (GEFs). Denaturation experiments of the protein with a chaotropic reagent show
      that both functional states coexist during folding and unfolding. Application of
      high pressure represents another perturbation of the energy landscape, leading to
      an increased population of the state 1 as observed by NMR spectroscopy. The
      specific volume difference between the two states DeltaV(12) is 17.2 +/- 0.5 mL
      mol(-1), indicating that state 1 represents a more open conformation of the
      protein. The free energies of stabilization for state 1 and state 2 at 278 K can
      be determined as 8.3 and 9.8 kJ mol(-1), respectively.

PMID- 19856910
TI  - Phage wrapping with cationic polymers eliminates nonspecific binding between M13
      phage and high pI target proteins.
AB  - M13 phage have provided scaffolds for nanostructure synthesis based upon self
      assembled inorganic and hard materials interacting with phage-displayed peptides.
      Additionally, phage display has been used to identify binders to plastic, TiO(2),
      and other surfaces. However, synthesis of phage-based materials through the
      hybridization of soft materials with the phage surface remains unexplored. Here,
      we present an efficient "phage wrapping" strategy for the facile synthesis of
      phage coated with soluble, cationic polymers. Polymers bearing high positive
      charge densities demonstrated the most effective phage wrapping, as shown by
      assays for blocking nonspecific binding of the anionic phage coat to a high pI
      target protein. The results establish the functional group requirements for
      hybridizing phage with soft materials and solve a major problem in phage display
      nonspecific binding by the phage to high pI target proteins.

PMID- 19856911
TI  - Exploiting substrate stress to modify nanoscale SAM patterns.
AB  - We describe a simple method based on postadsorption substrate stress induction to
      modify and control nanoscale phase-separated patterns formed in self-assembled
      monolayers. We show using mesoscale computer simulations and experiments that
      this method helps quickly progress a kinetically arrested patchy pattern into the
      equilibrium striped pattern, which is otherwise difficult to access. This work
      also establishes the role of curvature in the formation of aligned stripes
      several molecules wide on spherical nanoparticles and nanocylinders.

PMID- 19856912
TI  - Growth of tetrahexahedral gold nanocrystals with high-index facets.
AB  - Elongated tetrahexahedral Au nanocrystals have been grown in high yields using a
      seed-mediated growth method. Morphological and structural characterizations show
      that these Au nanocrystals are single-crystalline and enclosed by 24 high-index
      {037} facets. They are more electrochemically active than octahedral Au
      nanocrystals that are enclosed by 8 low-index {111} facets. To date, there have
      been only a few reports of metal nanocrystals that are enclosed exclusively by
      high-index facets, including trisoctahedral Au nanocrystals enclosed by 24 {122}
      facets and tetrahexahedral Pt nanocrystals enclosed by 24 {037} facets. Our
      tetrahexahedral Au nanocrystals will be an important addition to the family of
      metal nanocrystals that are enclosed exclusively by high-index facets and will
      also be useful for fundamental catalytic studies on metal nanocrystals.

PMID- 19856914
TI  - Grape skin and seed proanthocyanidins from Monastrell x Syrah grapes.
AB  - In this study, the grape skin and seed proanthocyanidin profiles from Monastrell
      x Syrah grape (Vitis vinifera L.) crosses were determined. Concentration and
      compositional information in extracts was determined by reversed-phase HPLC after
      acid-catalyzed cleavage in the presence of excess phloroglucinol. In general, the
      proanthocyanidin compositions of crosses were qualitatively similar to those of
      Monastrell and Syrah, but, quantitatively, differences were observed. Consistent
      with transgressive segregation, the proanthocyanidin concentration in some
      crosses exceeded that in either parent. To the best of the authors' knowledge,
      this is the first study to provide information on the inheritance of
      proanthocyanidin features from V. vinifera cultivars. The overall objective of
      this study is to develop new varieties that are well-adapted to our agro
      ecological conditions, as Monastrell is, and with a proanthocyanidin profile that
      will result in high-quality wines.

PMID- 19856915
TI  - Flow injection analysis-isotope ratio mass spectrometry for bulk carbon stable
      isotope analysis of alcoholic beverages.
AB  - A new method for bulk carbon isotope ratio determination of water-soluble samples
      is presented that is based on flow injection analysis-isotope ratio mass
      spectrometry (FIA-IRMS) using an LC IsoLink interface. Advantages of the method
      are that (i) only very small amounts of sample are required (2-5 microL of the
      sample for up to 200 possible injections), (ii) it avoids complex sample
      preparation procedures such as needed for EA-IRMS analysis (only sample dilution
      and injection,) and (iii) high throughput due to short analysis times is possible
      (approximately 15 min for five replicates). The method was first tested and
      evaluated as a fast screening method with industrially produced ethanol samples,
      and additionally the applicability was tested by the measurement of 81 alcoholic
      beverages, for example, whiskey, brandy, vodka, tequila, and others. The minimal
      sample concentration required for precise and reproducible measurements was
      around 50 microL L(-1) ethanol/water (1.71 mM carbon). The limit of repeatability
      was determined to be r=0.49%. FIA-IRMS represents a fast screening method for
      beverage authenticity control. Due to this, samples can be prescreened as a
      decisive criterion for more detailed investigations by HPLC-IRMS or multielement
      GC-IRMS measurements for a verification of adulteration.

PMID- 19856916
TI  - Amphoteric amino aldehydes reroute the aza-Michael reaction.
AB  - Amphoteric amino aldehydes, which exist as stable dimers, participate in an aza
      Michael/aldol domino reaction with alpha,beta-unsaturated aldehydes to afford
      stable 1,5-aminohydroxyaldehydes in high yields and diastereoselectivies. The
      reaction outcome hinges upon the dimeric nature of amphoteric amino aldehydes and
      the orthogonality between the NH aziridine and the two aldehyde functionalities
      during the reaction. Through the use of reaction conditions that disfavor dimer
      dissociation, the aza-Michael process has been directed toward a novel 8
      (enolendo)-exo-trig cyclization. The results described herein further demonstrate
      the potential of amphoteric molecules in reaction discovery.

PMID- 19856917
TI  - Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression
      through downregulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways.
AB  - Rosmanol is a natural polyphenol from the herb rosemary (Rosmarinus officinalis
      L.) with high antioxidant activity. In this study, we investigated the inhibitory
      effects of rosmanol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7
      cells induced by lipopolysaccharide (LPS). Rosmanol markedly inhibited LPS
      stimulated iNOS and COX-2 protein and gene expression, as well as the downstream
      products, NO and PGE2. Treatment with rosmanol also reduced translocation of the
      nuclear factor-kappaB (NF-kappaB) subunits by prevention of the degradation and
      phosphorylation of inhibitor kappaB (IkappaB). Western blot analysis showed that
      rosmanol significantly inhibited translocation and phosphorylation of NF-kappaB,
      signal transducer and activator of transcription-3 (STAT3), and the protein
      expression of C/EBPbeta and C/EBPdelta. We also found that rosmanol suppressed
      LPS-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase
      (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Our results
      demonstrate that rosmanol downregulates inflammatory iNOS and COX-2 gene
      expression by inhibiting the activation of NF-kappaB and STAT3 through
      interfering with the activation of PI3K/Akt and MAPK signaling. Taken together,
      rosmanol might contribute to the potent anti-inflammatory effect of rosemary and
      may have potential to be developed into an effective anti-inflammatory agent.

PMID- 19856918
TI  - Characterization of commercial inactive dry yeast preparations for enological use
      based on their ability to release soluble compounds and their behavior toward
      aroma compounds in model wines.
AB  - The characterization of commercial enological inactive dry yeast (IDY) with
      different applications in wine production has been carried out. This study was
      based on the yeast's ability to release soluble compounds (high molecular weight
      nitrogen, free amino nitrogen, peptidic nitrogen, free amino acids, and
      polysaccharides) into model wines and on its behavior toward the volatility of
      seven wine aroma compounds. Important differences in soluble compounds released
      into the model wines supplemented with commercial IDY were found, with the free
      amino acids being among the most released. The volatility of most of the aroma
      compounds was affected by the addition of IDY preparations at a concentration
      usually employed during winemaking. The extent of this effect was dependent on
      the physicochemical characteristics of the aroma compound and on the length of
      time the IDY preparations remained in contact with the model wines. Whereas
      shorter contact times (2, 4, and 6 days) mainly promoted a "salting-out" effect,
      longer exposure (9 and 13 days) provoked a retention effect, with the consequent
      reduction of aroma compounds in the headspace. The use of different commercial
      preparations also promoted different effects toward the aroma compounds that may
      be at least in part due to differences in their ability to release soluble
      compounds of yeast origin into the wines.

PMID- 19856919
TI  - Novel macrocyclic inhibitors of hepatitis C NS3/4A protease featuring a 2-amino
      1,3-thiazole as a P4 carbamate replacement.
AB  - Our laboratories recently reported the discovery of P2-P4 macrocyclic inhibitors
      of HCV NS3/4A protease, characterized by high levels of potency and liver
      exposure. Within this novel class of inhibitors, we here describe the
      identification of a structurally diverse series of compounds featuring a 2-amino
      1,3-thiazole as replacement of the carbamate in P4. Optimization studies focused
      on structural modifications in the P3, P2, and P1 regions of the macrocycle as
      well as on the linker chain and resulted in the discovery of several analogues
      characterized by excellent levels of enzyme and cellular activity. Among these,
      compound 59 displayed an attractive pharmacokinetic profile in preclinical
      species and showed sustained liver levels following oral administration in rats.

PMID- 19856920
TI  - Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of
      the mouse double minute 2-tumor protein 53 protein-protein interaction.
AB  - Tumor protein 53 (p53) is a critical regulator of cell cycle and apoptosis that
      is frequently disabled in human tumors. In many tumor types, p53 is deleted or
      mutated, but in others p53 is inactivated by overexpression or amplification of
      its negative regulator mouse double minute 2 (MDM2). A high-throughput screening
      effort identified 6,7-bis(4-bromophenyl)-7,12-dihydro-6H-chromeno[4,3
      d][1,2,4]triazolo[1,5-a]pyrimidine as a potent inhibitor of the MDM2-p53 protein
      protein interaction. This screening hit was found to be chemically unstable and
      difficult to handle due to poor DMSO solubility. Co-crystallization with the
      target protein helped to direct further optimization and provided a tractable
      lead series of novel MDM2-p53 inhibitors. In cellular assays, these compounds
      were shown to upregulate p53 protein levels and p53 signaling and to cause p53
      dependent inhibition of proliferation and apoptosis.

PMID- 19856921
TI  - Synthesis, structure-activity relationships, and characterization of novel
      nonsteroidal and selective androgen receptor modulators.
AB  - Herein we describe the discovery of ACP-105 (1), a novel and potent nonsteroidal
      selective androgen receptor modulator (SARM) with partial agonist activity
      relative to the natural androgen testosterone. Compound 1 was developed from a
      series of compounds found in a HTS screen using the receptor selection and
      amplification technology (R-SAT). In vivo, 1 improved anabolic parameters in a 2
      week chronic study in castrated male rats. In addition to compound 1, a number of
      potent antiandrogens were discovered from the same series of compounds whereof
      one compound, 13, had antagonist activity at the AR T877A mutant involved in
      prostate cancer.

PMID- 19856922
TI  - Molecular design, synthesis, and properties of highly fluorescent polyimides.
AB  - To develop a molecular design concept for highly fluorescent polyimides (PIs),
      ultraviolet-visible optical absorption spectra and fluorescent
      excitation/emission spectra of PI thin films were extensively investigated with
      the aid of density functional theory calculations. It was clarified that fully
      aromatic PIs (Ar-PIs) have strong charge transfer (CT) interactions, and their
      lowest excited states are attributable to CT(pi-pi*) states which emit weak
      fluorescence. The CT interactions in PIs are effectively suppressed by using
      alicyclic diamines as the source material, regardless of the dianhydride
      structure. This is due to the nonaromatic nature and weak electron-donating
      property of alicyclic diamines. The lowest excited states of Al-PIs derived from
      aromatic dianhydrides having delocalized pi conjugation and an alicyclic diamine
      are attributable to LE(pi-pi*) states which emit strong fluorescence. In
      particular, Al-PIs having ether (-O-) linkages in the dianhydride moiety
      demonstrated the strongest blue photoluminescence with a quantum efficiency of
      11%. This is explainable by the fact that the bent and rotatable diphenyl ether
      structure prevents dense chain packing which effectively weakens the
      fluorescence. However, the lowest excited states of Al-PIs derived from
      dianhydrides with localized pi conjugation and an alicyclic diamine are
      attributable to LE(n-pi*) states which emit quite weak fluorescence. These
      results indicate that the Al-PIs synthesized from alicyclic diamines and aromatic
      dianhydrides having delocalized conjugation with nonplanar structures are
      potential candidates for thermally stable polymers which emit strong fluorescence
      in the visible region, i.e., "highly fluorescent polyimides".

PMID- 19856924
TI  - Tetraarylphosphonium salts as soluble supports for oxidative catalysts and
      reagents.
AB  - Tetraarylphosphonium (TAP)-supported DMSO, TEMPO, and DIB reagents were
      synthesized and used for the oxidation of alcohols, including Swern oxidation and
      for the alpha-acetoxylation of ketones. By taking advantage of the predictable
      solubility properties of the TAP unit, simple precipitation and filtration of the
      phosphonium moiety permit complete separation of the desired oxidation products.
      This paper describes the preparation of these three TAP-supported oxidative
      reagents and their activity in the aforementioned oxidative transformations.
      Furthermore, we have demonstrated that these reagents can be recycled directly
      when used in catalytic processes and following regeneration when used in
      stoichiometric processes.

PMID- 19856923
TI  - Neuroprotective and cholinergic properties of multifunctional glutamic acid
      derivatives for the treatment of Alzheimer's disease.
AB  - Novel multifunctional compounds have been designed, synthesized, and evaluated as
      potential drugs for the treatment of Alzheimer's disease (AD). With an L-glutamic
      moiety as a suitable biocompatible linker, three pharmacophoric groups were
      joined: (1) an N-benzylpiperidine fragment selected to inhibit
      acetylcholinesterase by interacting with the catalytic active site (CAS), (2) an
      N-protecting group of the amino acid, capable of interacting with the
      acetylcholinesterase (AChE)-peripheral anionic site (PAS) and protecting neurons
      against oxidative stress, and (3) a lipophilic alkyl ester that would facilitate
      penetration into the central nervous system by crossing the blood-brain barrier.
      At submicromolar concentration, they inhibit AChE and butyrylcholinesterase
      (BuChE) of human origin, displace the binding of propidium iodide from the PAS of
      AChE, and could thus inhibit Abeta aggregation promoted by AChE. They also
      display neuroprotective properties against mitochondrial free radicals, show low
      toxicity, and could be able to penetrate into the CNS.

PMID- 19856925
TI  - Oxazaborolidinone-catalyzed enantioselective Friedel-Crafts alkylation of furans
      and indoles with alpha,beta-unsaturated ketones.
AB  - allo-Threonine-derived oxazaborolidinone (10 mol %) catalyzes the Friedel-Crafts
      alkylation of furans and indoles with simple acyclic alpha,beta-unsaturated
      ketones to give products with high yield and high enantioselectivity. The use of
      N,N-dimethylaniline (2.5-10 mol %) as an additive is essential for
      enantioselectivity.

PMID- 19856926
TI  - A Pd-catalyzed heteroannulation approach to 2,3-disubstituted furo[3,2
      c]coumarins.
AB  - The Pd-catalyzed cyclofunctionalization of 3-alkynyl-4-methoxycoumarins with aryl
      halides resulted in the selective formation of 3-arylfuro[3,2-c]coumarins in lieu
      of the expected regioisomeric 3-arylfuro[2,3-b]chromones. A mechanism involving
      the linear to angular rearrangement of a Pd-containing furan intermediate was
      proposed.

PMID- 19856927
TI  - General synthesis of highly functionalized cyclopentane segments for the
      preparation of jatrophane diterpenes.
AB  - Short and efficient syntheses of two diastereomeric cyclopentane segments present
      in most jatrophane diterpenes were achieved. Key steps are a stereoselective C-2
      elongation, an RCM, and a hydroboration reaction. An orthogonal protecting group
      methodology makes these segments useful building blocks for diterpene synthesis.

PMID- 19856928
TI  - Four-component reactions toward fused heterocyclic rings.
AB  - A multicomponent reaction between H(2), CO, an unsaturated carboxylic acid
      derivative, and binucleophiles has been discovered. This process represents a
      combination of diversity-oriented synthesis and multicomponent reactions
      including amidation and hydroformylation, followed by nucleophilic addition to an
      N-acyliminium ion allowing the generation of six new bonds. Using pi
      nucleophiles, the sequence turns into a multicomponent Pictet-Spengler reaction.

PMID- 19856929
TI  - Palladium-catalyzed intramolecular aminofluorination of unactivated alkenes.
AB  - A novel palladium-catalyzed intramolecular oxidative aminofluorination of
      unactivated alkenes has been developed, in which AgF was used as a key
      fluorinating reagent and PhI(OPiv)(2) as oxidant. The reaction afforded vicinal
      fluoroamine products with very high regioselectivity. A Pd(II/IV) catalytic cycle
      was proposed, and preliminary mechanistic studies indicated that direct reductive
      elimination of Pd(IV) intermediates is favored, albeit competing with S(N)2
      nucleophilic attack by fluorine, to form a C-F bond.

PMID- 19856930
TI  - Nanorings of self-assembled fullerene C(70) as templating nanoreactors.
AB  - Micelles, polyelectrolytes, peptides, and plasmid DNA with well-defined growth
      cavities can function as templates for the synthesis of metal nanocrystals. In a
      similar way, carbon-based toroidal 'nanoreactors' composed of clustered
      fullerenes could be used to synthesize nanohybrids by forming metal nanocrystals
      within the confines of the ring.

PMID- 19856931
TI  - Slightly viscous amino acid ionic liquids: synthesis, properties, and
      calculations.
AB  - Slightly viscous N-alkyl-substituted glycine ester ionic liquids were prepared
      via alkylation of glycine ethyl esters with appropriate haloalkanes followed by
      anion exchange with lithium bis(trifluoromethanesulfonyl)amide. These ionic
      liquids have been characterized by IR, NMR, elemental analysis, thermal
      stability, phase behavior, viscosity, and density. Compound 9 crystallizes in the
      monoclinic system, P2(1)/c. The viscosities of the N,N,N-trialkyl-substituted
      glycine ester ionic liquids (6, 8, 10) are in the approximately 200 to 400 cP
      range at 25 degrees C. While exhibiting liquid characteristics analogous to the
      traditional heterocyclic ionic liquids, these new liquids are much less viscous
      than known amino acid ionic liquids. The correlation of viscosity and temperature
      was determined. To understand the influence of the alkyl and ester-substituted
      groups on viscosity, the electronic distributions and the electrostatic potential
      surfaces of the glycine-based cations, including glycine (Gly(+)), glycine ethyl
      ester (GlyET(+)), N,N-dimethyl glycine (DMGly(+)), N,N-dimethyl glycine ethyl
      ester (DMGlyET(+)), N,N-dimethyl-N-propyl glycine ethyl ester (DMPGlyET(+)), N,N
      dimethyl-N-3-fluoropropyl glycine ethyl ester (DMPFGlyET(+)), and N-butyl-N,N
      dimethyl glycine ethyl ester (DMBGlyET(+)) cations have been investigated and
      analyzed. The possible effects on the viscosity coming from the intermolecular
      interactions arising from Coulomb interactions, hydrogen bonding, polarizability
      effects, and van der Waals interactions are considered.

PMID- 19856933
TI  - Study of the structural and electronic properties of Rh(N) and Ru(N) clusters (N
      < 20) within the density functional theory.
AB  - Using the density-functional theory (DFT) with the generalized gradient
      approximation to exchange and correlation, we compute the geometries, electronic
      structure, and related properties of free-standing rhodium and ruthenium atomic
      clusters with sizes below 20 atoms. We explore different structural and spin
      isomers per size, for which we determine the interatomic distances, binding
      energy, magnetic moment, HOMO-LUMO gap, and electric dipole moment. For many
      sizes, different implementations of DFT predict different properties for the
      lowest-energy isomers, thus illustrating the complex nature of these 4d
      transition metal elements at the nanoscale. We discuss our results for rhodium
      clusters in the context of recent electric deflection measurements.

PMID- 19856932
TI  - Temperature dependence of oxygen evolution in the thylakoid membrane: thermal
      transitions above 273 K in steady-state conditions.
AB  - The temperature dependence of electron transport through photosystem II (PSII),
      measured as oxygen evolution, was investigated in thylakoid membranes irradiated
      with white light of 450 micromol of photons/(m(2) x s). The experiments were
      performed in steady-state conditions at temperatures between 273 and 303 K. The
      results show discontinuities, or thermal transitions, in the temperature-response
      curves of oxygen evolution. The experimental data was examined with the Marcus
      theory of electron transfer modified to take into account the oxygen evolution
      discontinuities. For this purpose, the Gibbs free energy of activation of the
      electron transfer reaction, DeltaG(o), is replaced in the classical Marcus
      equation with the expression DeltaH(o) - TDeltaS(o), where H(o) and DeltaS(o) are
      respectively the enthalpy and entropy of activation, and T is the temperature in
      kelvin. The result of the derivation is a summation of j Gaussian functions, or
      states, OE = 69 250 summation operator(j){(V(DA)(4)/lambdaT)(1/2) exp[-(T(max) -
      T)(2)/2Tsigma(o)(2)]}(j) (eq 1), where OE is expressed in micromol oxygen
      evolution.(mg Chl x h)(-1), and V(DA) is the electronic coupling matrix element
      between electron donor (D) and acceptor (A) wave functions, lambda the
      reorganization free energy, k(B) the Boltzmann constant, T(max) = (DeltaH(o) +
      lambda)/DeltaS(o), sigma(o) = (2k(B)lambda/DeltaS(o2))(1/2), and sigma =
      T(1/2)sigma(o) is the standard deviation of the Gaussian band. The mathematical
      simulations revealed the presence of six thermal transitions, or Gaussian bands
      with maxima at 275.3, 281.2, 286.4, 291.4, 297.1, and 302.4 K. The resolution of
      the Gaussian bands is about 0.55 owing to multiple band superpositions. The
      theoretical analyses showed that (i) the oxygen evolution in PSII is essentially
      dependent on V(DA)(2)/(lambdaT)(1/2) in the pre-exponential term of the modified
      Marcus equation (eq 1), and (ii) the reorganization energy, lambda, decreases
      exponentially with increasing temperature, and is also dependent on the electron
      donor-acceptor distance. It is concluded that the temperature dependence of the
      large enhancement of oxygen evolution observed in this work originates, at least
      partly, in heat-induced structural rearrangements in the photosystem II reaction
      center.

PMID- 19856935
TI  - Structural and electronic properties of poly(thiaheterohelicene)s.
AB  - Quantum chemical methods have been applied on model oligomers of
      poly(thiaheterohelicene)s to investigate the structural and electronic properties
      of these systems. Specifically, the properties of the helical structures found
      for poly(heterohelicene) and poly(methyl-sulfonium), which were calculated using
      density functional theory calculations, are in good agreement with available
      experimental data. The geometrical parameters obtained for poly(methyl-sulfonium)
      reflect the enlargement of the inner carbon-carbon bond lengths at the thiophene
      rings, which are those closer to the helical screw axes, and lead to reduce their
      aromaticity of such heterocycles. On this basis, a relationship between the
      aromaticity and the lowest pi-pi* transition energy has been established.
      Finally, the lowest pi-pi* transitions have been extrapolated for infinite
      polymer chains of poly(heterohelicene) and poly(methyl-sulfonium) using different
      theoretical approaches.

PMID- 19856936
TI  - Growth mode transition of tetrahydrofuran clathrate hydrates in the guest/host
      concentration boundary layer.
AB  - Clathrate hydrates are known to form a thin film along a guest/host boundary. We
      present here the first report of tetrahydrofuran (THF) clathrate hydrate
      formation in a THF/water concentration boundary layer. We found that the THF
      water system also forms a hydrate film separating the guest/host phases. The
      lateral growth rate of the film increases as supercooling increases. The
      thickness of the film at the growth tip decreases as supercooling and the lateral
      growth rate increase. These tendencies are consistent with reports of experiments
      for other hydrates and predictions of heat-transfer models. After film formation
      and slight melting, two types of growth modes are observed, depending on
      temperature T. At T = 3.0 degrees C, the film slowly thickens. The thickening
      rate is much lower than the lateral growth rate, as reported for other hydrates.
      At T < or = 2.0 degrees C, however, the growth mode transitions spontaneously
      from film growth to continuous nucleation, and an agglomerate of small
      polycrystalline hydrates forms in each phase. Grain boundaries in the film and
      pore spaces in the agglomerate act as paths for permeation of each liquid. Timing
      when continuous nucleation starts is dominantly controlled by the time of
      initiation of liquid permeation through the film. Digital particle image
      velocimetry analysis of the agglomerate shows that it expands not by growth at
      the advancing front but rather by continuous nucleation in the interior.
      Expansion rates of the agglomerate tend to be higher for the cases of
      multipermeation paths in the film and the thinner film. We suppose that the
      growth mode transition to continuous nucleation is caused by the memory effect
      due to slight melting of the hydrate film.

PMID- 19856934
TI  - Effect of U on the electronic properties of neodymium gallate (NdGaO3):
      theoretical and experimental studies.
AB  - We have performed a density functional calculation for the centrosymmetric
      neodymium gallate using a full-potential linear augmented plane wave method with
      the LDA and LDA+U exchange correlation. In particular, we explored the influence
      of U on the band dispersion and optical transitions. Our calculations show that U
      = 0.55 Ry gives the best agreement with our ellipsometry data taken in the VUV
      spectral range with a synchrotron source. Our LDA+U (U = 0.55) calculation shows
      that the valence band maximum (VBM) is located at T and the conduction band
      minimum (CBM) is located at the center of the Brillouin zone, resulting in a wide
      indirect energy band gap of about 3.8 eV in excellent agreement with our
      experiment. The partial density of states show that the upper valence band
      originates predominantly from Nd-f and O-p states, with a small admixture of Nd
      s/p and Ga-p B-p states, while the lower conduction band prevailingly originates
      from the Nd-f and Nd-d terms with a small contribution of O-p-Ga-s/p states. The
      Nd-f states in the upper valence band and lower conduction band have a
      significant influence on the energy band gap dispersion which is illustrated by
      our calculations. The calculated frequency dependent optical properties show a
      small positive uniaxial anisotropy.

PMID- 19856937
TI  - Two-photon three-dimensional optical storage memory.
AB  - We describe the design and construction of ultrahigh capacity three-dimensional,
      3D, optical storage devices that operate by two-photon absorption. The molecular
      systems and their properties that are used as two photon media for writing and
      one photon for accessing the stored information within the volume of the device
      are presented in some detail and the nonlinear two-photon absorption mechanism is
      briefly visited. The optical system and its components, which facilitated writing
      and reading, are also described and the bit density, bit error rate, store and
      access speeds, cycle times, and stability of the materials under various
      experimental conditions are also topics addressed in this review. The first ever
      storage of terabyte data in a removable storage disk is described in detail.

PMID- 19856940
TI  - Comprehensive analysis on the structure and proton switch in H+ (CH3OH)m(H2O)n (m
      + n = 5 and 6).
AB  - Theoretical and experimental methods were integrated to investigate the
      structures of H(+)(CH(3)OH)(m)(H(2)O)(n) clusters for m + n = 5 and 6. An
      effective theoretical approach is presented to search for extensive sets of
      structural isomers using an empirical model and substitution schemes. Stable
      isomers were then reoptimized by the B3LYP level of computations with the 6-31+G*
      basis set. Canonical averages of these structural isomers were analyzed by
      harmonic superposition approximation (HSA) to study their finite temperature
      behavior and enable quantitative comparisons with experimental results. Thermal
      energy is found to have a significant effect on the structure of these clusters.
      Our calculations show that cyclic isomers are preferred at low temperature, while
      linear and tree forms become more favorable at high temperature (>200 K).
      Furthermore, we found that proton can reside on both water and methanol ion cores
      and the proton switch is associated with morphology change. Experimental IR
      spectra in the free OH stretching region were also obtained and compared with
      calculated spectra.

PMID- 19856938
TI  - Photodegradation of dibenzoylmethanes: potential cause of photocontact allergy to
      sunscreens.
AB  - One of the most frequently observed photoallergens today is the sunscreen agent 4
      tert-butyl-4'-methoxy dibenzoylmethane (1a). The structurally similar compound, 4
      isopropyldibenzoylmethane (1b), was a common cause of sunscreen allergy in the
      eighties and early nineties but was removed from the market in 1993 and replaced
      with dibenzoylmethane 1a. We have studied the photodegradation of the
      dibenzoylmethane 1a, to better understand how these substances cause an immune
      reaction. Several expected degradation products were formed and identified. Of
      these, arylglyoxals and benzils were of particular interest because they were
      unexplored as potential contact allergens. The allergenic potential of
      photodegraded 1a was evaluated by screening the formed arylglyoxals and benzils
      for their sensitizing capacity in the murine local lymph node assay. The
      arylglyoxals were found to be strong sensitizers. They were also found to be
      highly reactive toward the nucleophile arginine, which indicates that the
      immunogenic hapten-protein complex could be formed via an electrophilic
      nucleophilic pathway. By varying the electron-withdrawing or -donating capacity
      of the substituent in the para position of the arylglyoxal, the electronic
      effects were shown to have no significant impact on either the sensitizing or the
      electrophilic power of arylglyoxals. Thus, a change in the substitution pattern
      of the parent dibenzoylmethane will not influence the sensitizing capacity of the
      products formed from them upon photodegradation. Furthermore, the combined
      studies of benzils, using the local lymph node assay and a cell proliferation
      assay, indicate that the benzils are cytotoxic rather than allergenic. Taken
      together, this study presents strong indication that photocontact allergy to
      dibenzoylmethanes is caused by the arylglyoxals that are formed upon
      photodegradation.

PMID- 19856941
TI  - New reversible crystal-to-crystal conversion of a mixed-ligand lead(II)
      coordination polymer by de- and rehydration.
AB  - A reversible crystal-to-crystal transformation of a new 2D lead(II) coordination
      polymer with the ligand 4-pyridinecarboxylic acid (4-Hpyc), [Pb(4
      pyc)(Br)(H(2)O)](n) (1) to [Pb(4-pyc)(Br)](n) (2) by de- and rehydration, has
      been observed, and the structures of 1 and 2 have been determined by single
      crystal X-ray diffraction. The thermal stabilities of compounds 1 and 2 were
      studied by thermal gravimetric and differential thermal analyses. Powder X-ray
      diffraction experiments showed that the structural transformation occurs in the
      batch powder samples and leads to monophasic products.

PMID- 19856942
TI  - Photocurrent induced by nonradiative energy transfer from nanocrystal quantum
      dots to adjacent silicon nanowire conducting channels: toward a new solar cell
      paradigm.
AB  - We report the observation of photocurrent in silicon nanowires induced by
      nonradiative resonant energy transfer (NRET) from adjacent layers of lead sulfide
      nanocrystal quantum dots using time-resolved photocurrent measurements. This
      demonstration supports the feasibility of a new solar cell paradigm (Lu, S.;
      Madhukar, A. Nano Lett. 2007, 7, 3443-3451) that exploits NRET between efficient
      photon absorbers and adjacent nanowire/quantum well high-mobility charge
      transport channels and could offer a viable alternative to the limitations of
      carrier transport and collection faced by excitonic solar cells.

PMID- 19856943
TI  - Valence ionization of water clusters: from isolated molecules to bulk.
AB  - The valence photoelectron spectra of water clusters are studied experimentally
      and by ab initio calculations. The size dependence of the vertical ionization
      energy of the outermost orbitals is explicitly shown. A shift toward lower values
      is observed. For small cluster sizes, it can be rationalized as an effect of
      charge delocalization as the system is becoming more extended. Ionization
      energies of larger clusters decrease linearly with inverse cluster radius and
      asymptotically approach the value of liquid water. In the calculations, we apply
      a reflection principle approach based on sampling a quantum mechanical
      distribution of different initial-state geometries to clusters. An excellent
      agreement of peak shapes calculated thus with measured ones is shown. Using
      additional polarization fields, the extension of this approach to the
      photoionization of liquid water is demonstrated. Upon deuteration of the water
      clusters, we experimentally and theoretically find slightly larger absolute
      values of the vertical ionization energies. We suggest that the measurement of
      electron ionization energies can be used as an alternative means to characterize
      water cluster sizes, which can complement the use of scaling laws.

PMID- 19856944
TI  - Asymmetric addition of alkenylstannanes to alkylidene Meldrum's acids.
AB  - Herein, we describe enantioselective addition of alkenyltin reagents possessing a
      reactive and sensitive allylic functionality not readily available to other
      classes of alkenyl metals. This method is enabled by the use of highly
      electrophilic alkylidene Meldrum's acids as acceptors and a cationic Rh(I)-diene
      complex as catalyst.

PMID- 19856945
TI  - Spontaneous fusion between the vesicles formed by A2n(B2)n type comb-like block
      copolymers with a semiflexible hydrophobic backbone.
AB  - The spontaneous vesicle formation and fusion of A(2n)(B(2))(n) (n = 2-10) type
      comb-like block copolymers with semiflexible hydrophobic backbone are studied via
      dissipative particle dynamics (DPD) simulations. By systemically varying the
      solvent condition, we construct a phase diagram to indicate the thermodynamically
      stable region for vesicles. The spontaneous fusion between the vesicles is
      studied, whose mechanism is as follows: first, a stalk is formed between the
      vesicles; then, the holes appear in both vesicles near the feet of the stalk;
      finally, the stalk bends to circle the holes and the fusion process is completed.
      This fusion pathway is similar to that observed in Monte Carlo simulations and
      dynamic self-consistent filed theory but different from those reported in coarse
      grained molecular dynamics and DPD simulations. The main reason for the
      difference may be attributed to the molecular structures used in different
      simulation techniques.

PMID- 19856946
TI  - Effective protocol for database similarity searching of heteronuclear single
      quantum coherence spectra.
AB  - The nuclear magnetic resonance (NMR) chemical shift exquisitely describes the
      chemical environment of the atoms in a molecule. Here we describe methods that
      utilize this information as an experimental probe to match 2D NMR heteronuclear
      single quantum coherence (HSQC) spectra of pure, unknown compounds to a database
      of known compounds. We implemented and compared two different approaches for
      similarity searching of HSQC spectra. According to our findings, our new discrete
      self-adaptive differential evolution method performs better than the previously
      published shifted grid, multiple resolution approach. The new method is provided
      in detail and comparisons have been performed for a set of HSQC spectra. The
      similarity comparison involves a peak-to-peak matching of different spectra,
      followed by a selection criterion and ranking to establish a level of match.

PMID- 19856947
TI  - High-resolution solid-state NMR investigation of the phase transition in
      decamethylferrocene-acenaphthenequinone charge-transfer complex.
AB  - A charge-transfer complex composed of decamethylferrocene (D) and
      acenaphthenequinone (A) was prepared. The material was a 1:1 neutral complex with
      a mixed-stack structure and exhibited a phase transition at -16 degrees C. High
      resolution (13)C and (1)H NMR spectroscopy revealed that an inclination of A with
      respect to D occurs below the phase-transition temperature. The (1)H spin
      diffusion rates of the complex undergoing high-speed magic-angle spinning (MAS)
      were measured to determine the shortest (1)H-(1)H distance r between D and A. To
      analyze the experimental results, we derived the analytical expression of the
      spin-diffusion rate W(z) for a homonuclear multispin system undergoing MAS. It
      was found that W(z) for the complex is proportional only to 1/r(6) under high
      speed MAS conditions. On the basis of this relationship and the crystal structure
      at 20 degrees C, it was determined that the shortest (1)H-(1)H distance r at 
      27.7 degrees C (below the phase transition temperature) is 0.4 A shorter than
      that at 20 degrees C. Given this information, a plausible model of the low
      temperature structure is discussed.

PMID- 19856948
TI  - A concise synthesis of castanospermine by the use of a transannular cyclization.
AB  - A nine-step synthesis of (+)-castanospermine has been accomplished in 22% overall
      yield from methyl alpha-D-glucopyranoside. The key transformations involve a zinc
      mediated fragmentation of benzyl-protected methyl 6-iodoglucopyranoside, ring
      closing olefin metathesis, and strain-release transannular cyclization to afford
      the indolizidine skeleton of the natural product.

PMID- 19856949
TI  - All-atom molecular dynamics study of a spherical micelle composed of N-acetylated
      poly(ethylene glycol)-poly(gamma-benzyl L-glutamate) block copolymers: a
      potential carrier of drug delivery systems for cancer.
AB  - An all-atom molecular dynamics simulation of a spherical micelle composed of
      amphiphilic N-acetylated poly(ethylene glycol)-poly(gamma-benzyl L-glutamate)
      (PEG-PBLG-Ac) block copolymers was performed in aqueous solution at 298.15 K and
      1 atm. Such copolymers have received considerable attention as carriers in drug
      delivery systems. In this study, we used copolymers consisting of 11 EG units and
      9 BLG units as models. Starting from the copolymers arranged spherically, the
      calculation predicted an equilibrium state consisting of a slightly elliptical
      micelle structure with a hydrophobic PBLG inner core and a hydrophilic PEG outer
      shell. The micelle structure was dynamically stable during the simulation, with
      the PEG blocks showing a compact helical conformation and the PBLG blocks an
      alpha-helix form. Multiple hydrogen bonds with solvent water molecules stabilized
      the helical conformation of the PEG blocks, leading to their hydration as shown
      by longer residence times of water molecules near the PEG ether oxygen atoms
      compared with that of bulk water. Some water molecules have also been found
      distributed within the hydrophobic core; they showed continuous exchange with
      bulk water during the simulation. Those molecules existed mostly as a cluster in
      spaces between the copolymers, forming hydrogen bonds among themselves as well as
      with the hydrophobic core through hydrophilic groups such as esters and amides.
      The water molecules forming hydrogen bonds with the micelle may play an important
      role in the stabilization of the micelle structure.

PMID- 19856950
TI  - Strategy of accelerated method development for high-throughput bioanalytical
      assays using ultra high-performance liquid chromatography coupled with mass
      spectrometry.
AB  - Here we report a strategy for rapid method development of high-throughput
      bioanalytical assays using ultra high-performance liquid chromatography coupled
      with tandem mass spectrometry (uHPLC-MS/MS). First, a data set was established
      for the removal of representative phospholipids under different sample treatments
      to guide subsequent method development for various compounds. The recovery
      information of the analyte(s) of interest under different extraction conditions
      was then obtained during method development. With the recovery profiles and the
      pre-established knowledge of phospholipids removal in place, an optimal
      extraction condition was identified to give not only a satisfactory recovery but
      also a good cleanup of the sample. A rapid LC or uHPLC method was developed
      without the need of extensive column wash after the elution of the analyte. This
      strategy was demonstrated through the method development of a uHPLC-MS/MS
      bioanalytical assay for the quantitation of ketoconazole in human plasma with
      liquid-liquid extraction using a hexane and ethyl acetate solvent system. The
      retention time for ketoconazole through an isocratic elution was 18 s. Good
      accuracy and precision were obtained. Assay ruggedness was demonstrated by
      consistent internal standard responses and retention time for 500 sequential
      injections. In addition, consistent results were obtained for incurred sample
      reanalysis.

PMID- 19856951
TI  - Fe5O5[B6O10(OH)3] x nH2O: wave-layered iron borate and frustrated
      antiferromagnetism.
AB  - The first layered iron borate, Fe(5)O(5)[B(6)O(10)(OH)(3)] x nH(2)O, has been
      prepared by the boric acid flux method. Its structure, determined by single
      crystal X-ray diffraction, contains a double FeO(6)-octahedral layer and an
      unusual [B(6)O(13)] chain. The rigid and cambered [B(6)O(13)] chains bend the
      octahedral layers, resulting in a wave-like and sandwiched structure.
      Crystallographic study indicates the structural modulation is mainly from the
      [B(6)O(13)] chains because of the insertion of water molecules in between.
      Nevertheless, FeO(6) layers in the average structure, which are well separated by
      borate chains, is still a reasonable model to understand the two-dimensional
      magnetism. The strong antiferromagnetic interactions and the complex Fe(3+)-net
      suggest a possible geometrically magnetic frustration, which may be the reason
      for the second-order temperature-induced magnetic transition at approximately 125
      K. The condensed Fe(3+) layers and the relatively low redox potential at about
      1.25 V versus Li(+)/Li show its potentials as an anodic material.

PMID- 19856952
TI  - Real-time TEM and kinetic Monte Carlo studies of the coalescence of decahedral
      gold nanoparticles.
AB  - We report on a real-time in situ TEM study of the coalescence of individual pairs
      of decahedral gold nanoparticles, which have been synthesized in solution. We
      observe the rate of growth of the neck that joins two particles during
      coalescence and compare this to classical continuum theory and to atomistic
      kinetic Monte Carlo simulations. We find good agreement between the observations
      and the simulations but not with the classical continuum model. This disagreement
      is attributed to the faceted nature of the particles.

PMID- 19856954
TI  - Pathways of energy flow in LHCII from two-dimensional electronic spectroscopy.
AB  - Photosynthetic light-harvesting complexes absorb energy and guide
      photoexcitations to reaction centers with speed and efficacy that produce near
      perfect efficiency. Light harvesting complex II (LHCII) is the most abundant
      light-harvesting complex and is responsible for absorbing the majority of light
      energy in plants. We apply two-dimensional electronic spectroscopy to examine
      energy flow in LHCII. This technique allows for direct mapping of excitation
      energy pathways as a function of absorption and emission wavelength. The
      experimental and theoretical results reveal that excitation energy transfers
      through the complex on three time scales: previously unobserved sub-100 fs
      relaxation through spatially overlapping states, several hundred femtosecond
      transfer between nearby chlorophylls, and picosecond energy transfer steps
      between layers of pigments. All energy is observed to collect into the
      energetically lowest and most delocalized states, which serve as exit sites. We
      examine the angular distribution of optimal energy transfer produced by this
      delocalized electronic structure and discuss how it facilitates the exit step in
      which the energy moves from LHCII to other complexes toward the reaction center.

PMID- 19856955
TI  - Lorneic acids, trialkyl-substituted aromatic acids from a marine-derived
      actinomycete.
AB  - A marine-derived actinomyces strain (NPS554) isolated from a marine sediment
      sample collected from Miyazaki Harbor, Japan, at a depth of 38 m yielded two
      trialkyl-substituted aromatic acids, lorneic acid A (1) and lorneic acid B (2).
      The structures of the lorneic acids, which were elucidated by spectroscopic
      analysis, differed only in the side-chain, which contained either a conjugated
      double bond or a benzylic alcohol. Their structural differences affected
      inhibition activities against phosphodiesterase 5.

PMID- 19856956
TI  - Temperature dependence of two key interstellar reactions of H(3)(+): O((3)P) +
      H(3)(+) and CO + H(3)(+).
AB  - The reactions of H(3)(+) with CO and with O((3)P) are the two most important
      reactions for the destruction of H(3)(+) in dense interstellar clouds. These two
      reactions are studied with sophisticated theoretical methods that should provide
      accurate predictions for the rate coefficients. The potential energy surfaces are
      studied with high-level electronic structure methods. For both reactions, simple
      long-range expansions are shown to be sufficiently accurate for predicting the
      kinetics at room temperature and lower. The kinetics is predicted from a
      combination of transition state theory, trajectory simulations, and master
      equation analysis. For the O((3)P) reaction, the interplay between the spin-orbit
      and the charge-quadrupole interactions is explicitly considered. For the CO
      reaction, we also consider the isomerization and decomposition dynamics of the
      two initially formed adducts. The final predictions, which are expected to be
      accurate to about 10 to 20%, are compared with the available experimental data.
      For the O((3)P) reaction, the predicted rate coefficient is accurately reproduced
      by the expression 1.14 x 10(-9) (T/300)(-0.156) exp(-1.41/T) cm(3) molecule(-1)
      s(-1) over the 5 to 400 K temperature range. For the CO reaction, the predicted
      rate coefficients for the H(2) + HCO(+) and H(2) + HOC(+) channels are accurately
      reproduced by the expressions 1.36 x 10(-9) (T/300)(-0.142) exp(3.41/T) and 8.49
      x 10(-10) (T/300)(0.0661) exp(-5.21/T) cm(3) molecule(-1) s(-1), respectively,
      over the 10 to 400 K temperature range. These revised rate coefficient
      expressions imply an increase in the destruction of H(3)(+) at temperatures that
      are typical of dense clouds (10-30 K) by a factor of 2.5 to 3.0.

PMID- 19856957
TI  - Chemical strategies for the synthesis of peptide-oligonucleotide conjugates.
AB  - The use of synthetic oligonucleotides and their mimics to inhibit gene expression
      by hybridizing with their target sequences has been hindered by their poor
      cellular uptake and inability to reach the nucleus. Covalent postsynthesis or
      solid-phase conjugation of peptides to oligonucleotides offers a possible
      solution to these problems. As feasible chemistry is a prerequisite for
      biological studies, development of efficient and reproducible approaches for
      convenient preparation of peptide-oligonucleotide conjugates has become a subject
      of considerable importance. The present review gives an account of the main
      synthetic methods available to prepare covalent conjugation of peptides to
      oligonucleotides.

PMID- 19856958
TI  - Theoretical study of Y(n)O(2) and Y(n)O(2)(-) (n = 1-8) clusters.
AB  - The structural, electronic, and magnetic properties of Y(n)O(2) and Y(n)O(2)(-)
      clusters, up to n = 8, have been systematically investigated by using the density
      functional approach. Our theoretical results show that the geometries of the
      ground-state neutral and anionic clusters are similar, except for n = 2. For the
      lowest-energy structures of the two systems, a two-dimensional to three
      dimensional structural transition is identified. In addition, the ionization
      potentials, electron affinities, electron detachment energies, and gaps are
      carefully investigated. Here, the calculated electron affinities and electron
      detachment energies are in good agreement with the experimental data, implying
      that the predictions of the ground-state configurations of these clusters are
      reliable. On the basis of the optimized structures, we investigate and discuss
      the magnetic properties of the two systems for the first time. (PACS numbers:
      75.50.Xx. 36.40.Cg,73.22.-f.).

PMID- 19856959
TI  - Structures and energetics for O2 formation in photosystem II.
AB  - Water oxidation, forming O(2) from water and sunlight, is a fundamental process
      for life on earth. In nature, the enzyme photosystem II (PSII) catalyzes this
      reaction. The oxygen evolving complex (OEC), the complex within PSII that
      catalyzes the actual formation of the O-O bond, contains four manganese atoms and
      one calcium atom connected by oxo bonds. Seven amino acid side chains in the
      structure, mostly carboxylates, are ligated to the metal atoms. In the study of
      many enzyme mechanisms, theoretical modeling using density functional theory has
      served as an indispensable tool. This Account summarizes theoretical research to
      elucidate the mechanism for water oxidation in photosynthesis, including the most
      recent findings. The development of successively larger models, ranging from 50
      atoms in the active site up to the present model size of 170 atoms, has revealed
      the mechanism of O(2) formation with increasing detail. The X-ray crystal
      structures of PSII have provided a framework for optimizing the theoretical
      models. By constraint of the backbone atoms to be at the same positions as those
      in the X-ray structures, the theoretical structures are in good agreement with
      both the measured electron density and extended X-ray absorption fine structure
      (EXAFS) interpretations. By following the structural and energetic changes in
      those structures through the different steps in the catalytic process, we have
      modeled the oxidation of the catalytic complex, the binding of the two substrate
      water molecules, and the subsequent deprotonations of those substrate molecules.
      In these models, the OEC forms a basin into which the water molecules naturally
      fit. These findings demonstrate that the binding of the second water molecule
      causes a reconstruction, results that are consistent with earlier EXAFS
      measurements. Most importantly, this Account describes a low-barrier mechanism
      for formation of the O-O bond, involving an oxygen radical that reacts with a mu
      oxo ligand of the OEC. Further research revealed that the oxygen radical is bound
      in the Mn(3)Ca cube rather than to the outside manganese. This Account provides
      detailed diagrams of the energetics of the different S-transitions both without
      and with a membrane gradient. An interesting detail of these reactions concerns
      the role of the tyrosine (Tyr(Z)), which appears as an intermediate radical in
      the oxidation of the OEC. By simple electrostatic arguments, these results show
      that the initial oxidation of Tyr(Z) is downhill for the first two transitions
      but uphill for the final ones. In these later transitions, the oxidation of the
      OEC is coupled to deprotonations of water.

PMID- 19856961
TI  - Pre-steady-state kinetic analysis of cis-3-chloroacrylic acid dehalogenase:
      analysis and implications.
AB  - Isomer-specific 3-chloroacrylic acid dehalogenases catalyze the hydrolytic
      dehalogenation of the cis- and trans-isomers of 3-chloroacrylate to yield
      malonate semialdehyde. These reactions represent key steps in the degradation of
      the nematocide, 1,3-dichloropropene. The kinetic mechanism of cis-3-chloroacrylic
      acid dehalogenase (cis-CaaD) has now been examined using stopped-flow and
      chemical-quench techniques. Stopped-flow analysis of the reaction, following the
      fluorescence of an active site tryptophan, is consistent with a minimal three
      step model involving substrate binding, chemistry, and product release. Chemical
      quench experiments show burst kinetics, indicating that product release is at
      least partially rate limiting. Global fitting of all of the kinetic results by
      simulation is best accommodated by a four-step mechanism. In the final kinetic
      model, the enzyme binds substrate with an immediate isomerization to an alternate
      fluorescent form and chemistry occurs, followed by the ordered release of two
      products, with the release of the first product as the rate-limiting step.
      Bromide ion is a competitive inhibitor of the reaction indicating that it binds
      to the free enzyme rather than to the enzyme with one product still bound. This
      observation suggests that malonate semialdehyde is the first product released by
      the enzyme (rate limiting), followed by halide. A comparison of the unliganded
      cis-CaaD crystal structure with that of an inactivated cis-CaaD where the prolyl
      nitrogen of Pro-1 is covalently attached to (R)-2-hydroxypropanoate provides a
      possible explanation for the isomerization step. The structure of the covalently
      modified enzyme shows that a seven-residue loop comprised of residues 32-38 is
      closed down on the active site cavity where the backbone amides of two residues
      (Phe-37 and Leu-38) interact with the carboxylate group of the adduct. In the
      unliganded form, the same loop points away from the active site cavity.
      Similarly, substrate binding may cause this loop to close down on the active site
      and sequester the reaction from the external environment.

PMID- 19856960
TI  - Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol
      intermediate for enediyne antitumor antibiotic C-1027 biosynthesis.
AB  - C-1027 is a chromoprotein antitumor antibiotic consisting of an apoprotein and
      the C-1027 chromophore. The C-1027 chromophore possesses four distinct structural
      moieties-an enediyne core, a deoxy aminosugar, a benzoxazolinate, and an (S)-3
      chloro-5-hydroxy-beta-tyrosine-the latter two of which are proposed to be
      appended to the enediyne core via a convergent biosynthetic strategy. Here we
      report the in vitro characterization of SgcF, an epoxide hydrolase from the C
      1027 biosynthetic gene cluster that catalyzes regio- and stereospecific
      hydrolysis of styrene oxide, serving as an enediyne core epoxide intermediate
      mimic, to form a vicinal diol. Abolishment of C-1027 production in the DeltasgcF
      mutant strain Streptomyces globisporus SB1010 unambiguously establishes that sgcF
      plays an indispensable role in C-1027 biosynthesis. SgcF efficiently hydrolyzes
      (S)-styrene oxide, displaying an apparent K(m) of 0.6 +/- 0.1 mM and k(cat) of 48
      +/- 1 min(-1), via attack at the alpha-position to exclusively generate the (R)
      phenyl vicinal diol, consistent with the stereochemistry of the C-1027
      chromophore. These findings support the role of SgcF in the proposed convergent
      pathway for C-1027 biosynthesis, unveiling an (R)-vicinal diol as a key
      intermediate. Interestingly, SgcF can also hydrolyze (R)-styrene oxide to afford
      preferentially the (R)-phenyl vicinal diol via attack at the beta-position,
      albeit with significantly reduced efficiency (apparent K(m) of 2.0 +/- 0.4 mM and
      k(cat) = 4.3 +/- 0.3 min(-1)). Although the latter activity unlikely contributes
      to C-1027 biosynthesis in vivo, such enantioconvergence arising from
      complementary regioselective hydrolysis of a racemic substrate could be exploited
      to engineer epoxide hydrolases with improved regio- and/or enantiospecificity.

PMID- 19856962
TI  - Unprecedented glycosidase activity at a lectin carbohydrate-binding site
      exemplified by the cyanobacterial lectin MVL.
AB  - Carbohydrate binding proteins, or lectins, are engendered with the ability to
      bind specific carbohydrate structures, thereby mediating cell-cell and cell
      pathogen interactions. Lectins are distinct from carbohydrate modifying enzymes
      and antibodies, respectively, as they do not carry out glycosidase or glycosyl
      transferase reactions, and they are of nonimmune origin. Cyanobacterial and algal
      lectins have become prominent in recent years due to their unique biophysical
      traits, such as exhibiting novel protein folds and unusually high carbohydrate
      affinity, and ability to potently inhibit HIV-1 entry through high affinity
      carbohydrate-mediated interactions with the HIV envelope glycoprotein gp120. The
      antiviral cyanobacterial lectin Microcystis viridis lectin (MVL), which contains
      two high affinity oligomannose binding sites, is one such example. Here we used
      glycan microarray profiling, NMR spectroscopy, and mutagenesis to show that one
      of the two oligomannose binding sites of MVL can catalyze the cleavage of chitin
      fragments (such as chitotriose) to GlcNAc, to determine the mode of MVL binding
      to and cleavage of chitotriose, to identify Asp75 as the primary catalytic
      residue involved in this cleavage, and to solve the solution structure of an
      inactive mutant of MVL in complex with this unexpected substrate. These studies
      represent the first demonstration of dual catalytic activity and carbohydrate
      recognition for discrete oligosaccharides at the same carbohydrate-binding site
      in a lectin. Sequence comparisons between the N- and C-domains of MVL, together
      with the sequences of new MVL homologues identified through bioinformatics,
      provide insight into the evolving roles of carbohydrate recognition.

PMID- 19856963
TI  - The structural basis of pregnane X receptor binding promiscuity.
AB  - The steroid and xenobiotic-responsive human pregnane X receptor (PXR) binds a
      broad range of structurally diverse compounds. The structures of the apo and
      ligand-bound forms of PXR are very similar, in contrast to most promiscuous
      proteins that generally adapt their shape to different ligands. We investigated
      the structural origins of PXR's recognition promiscuity using computational
      solvent mapping, a technique developed for the identification and
      characterization of hot spots, i.e., regions of the protein surface that are
      major contributors to the binding free energy. Results reveal that the smooth and
      nearly spherical binding site of PXR has a well-defined hot spot structure, with
      four hot spots located on four different sides of the pocket and a fifth close to
      its center. Three of these hot spots are already present in the ligand-free
      protein. The most important hot spot is defined by three structurally and
      sequentially conserved residues, W299, F288, and Y306. This largely hydrophobic
      site is not very specific and interacts with all known PXR ligands. Depending on
      their sizes and shapes, individual PXR ligands extend into two, three, or four
      more hot spot regions. The large number of potential arrangements within the
      binding site explains why PXR is able to accommodate a large variety of
      compounds. All five hot spots include at least one important residue, which is
      conserved in all mammalian PXRs, suggesting that the hot spot locations have
      remained largely invariant during mammalian evolution. The same side chains also
      show a high level of structural conservation across hPXR structures. However,
      each of the hPXR hot spots also includes residues with moveable side chains,
      further increasing the size variation in ligands that PXR can bind. Results also
      suggest a unique signal transduction mechanism between the PXR homodimerization
      interface and its coactivator binding site.

PMID- 19856964
TI  - Tandem application of virtual screening and NMR experiments in the discovery of
      brand new DNA quadruplex groove binders.
AB  - In the past decade, DNA G-quadruplexes have come into the limelight thanks to
      their biological implications and to their potential druggability in anticancer
      therapy. In particular, it has been found that small molecules that stabilize G
      quadruplex structures are effective inhibitors of telomerase which plays a
      critical role in tumorigenesis. So far, the quadruplex groove recognition, which
      is expected to give a higher degree of selectivity over the other DNA structures,
      has been demonstrated for very few compounds. Thus with the aim of detecting new
      and structurally diverse groove binders, a structure-based virtual screening
      campaign has been performed using the X-ray structure of the [d(TGGGGT)](4)
      quadruplex. Remarkable results were achieved, and six brand new different
      molecular entities have been found to interact with the groove through NMR
      experiments. The reported results will certainly stimulate further studies aimed
      at the design and optimization of new quadruplex-specific groove binders to be
      applied as anticancer agents and for other diseases.

PMID- 19856965
TI  - H2A.Z and H3.3 histone variants affect nucleosome structure: biochemical and
      biophysical studies.
AB  - Histone variants play important roles in regulation of chromatin structure and
      function. To understand the structural role played by histone variants H2A.Z and
      H3.3, both of which are implicated in transcription regulation, we conducted
      extensive biochemical and biophysical analysis on mononucleosomes reconstituted
      from either random-sequence DNA derived from native nucleosomes or a defined DNA
      nucleosome positioning sequence and recombinant human histones. Using established
      electrophoretic and sedimentation analysis methods, we compared the properties of
      nucleosomes containing canonical histones and histone variants H2A.Z and H3.3 (in
      isolation or in combination). We find only subtle differences in the compaction
      and stability of the particles. Interestingly, both H2A.Z and H3.3 affect
      nucleosome positioning, either creating new positions or altering the relative
      occupancy of the existing nucleosome position space. On the other hand, only
      H2A.Z-containing nucleosomes exhibit altered linker histone binding. These
      properties could be physiologically significant as nucleosome positions and
      linker histone binding partly determine factor binding accessibility.

PMID- 19856967
TI  - Stimuli-responsive reversible assembly of 2D and 3D metallosupramolecular
      architectures.
AB  - The discovery of interconvertible platinum coordination modes, which reveals and
      masks cis coordinating groups upon addition of acid and base, respectively, has
      been exploited to facilitate stimuli-responsive assembly and disassembly of both
      two- and three-dimensional metallosupramolecular architectures. Treatment of a
      binclear platinum complex with acid along with ditopic and tritopic donor ligands
      generated a molecular square and a trigonal prism, respectively, in good to high
      yield. These complexes were unambiguously identified using electrospray mass
      spectrometry, (1)H NMR spectroscopy, and X-ray crystallography. Both assemblies
      can be disassembled into their constituent parts simply by treatment with base,
      and the prism can be cycled between the assembled and disassembled states by the
      alternate addition of acid and base.

PMID- 19856966
TI  - (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta
      catenin agonist that increases bone formation rate.
AB  - A high-throughput screening campaign to discover small molecule leads for the
      treatment of bone disorders concluded with the discovery of a compound with a 2
      aminopyrimidine template that targeted the Wnt beta-catenin cellular messaging
      system. Hit-to-lead in vitro optimization for target activity and molecular
      properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2
      yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent
      pharmacokinetic properties and showed a dose dependent increase in the trabecular
      bone formation rate in ovariectomized rats following oral administration.

PMID- 19856969
TI  - Complex hydrides with (BH(4))(-) and (NH(2))(-) anions as new lithium fast-ion
      conductors.
AB  - Some of the authors have reported that a complex hydride, Li(BH(4)), with the
      (BH(4))(-) anion exhibits lithium fast-ion conduction (more than 1 x 10(-3) S/cm)
      accompanied by the structural transition at approximately 390 K for the first
      time in 30 years since the conduction in Li(2)(NH) was reported in 1979. Here we
      report another conceptual study and remarkable results of Li(2)(BH(4))(NH(2)) and
      Li(4)(BH(4))(NH(2))(3) combined with the (BH(4))(-) and (NH(2))(-) anions showing
      ion conductivities 4 orders of magnitude higher than that for Li(BH(4)) at RT,
      due to being provided with new occupation sites for Li(+) ions. Both
      Li(2)(BH(4))(NH(2)) and Li(4)(BH(4))(NH(2))(3) exhibit a lithium fast-ion
      conductivity of 2 x 10(-4) S/cm at RT, and the activation energy for conduction
      in Li(4)(BH(4))(NH(2))(3) is evaluated to be 0.26 eV, less than half those in
      Li(2)(BH(4))(NH(2)) and Li(BH(4)). This study not only demonstrates an important
      direction in which to search for higher ion conductivity in complex hydrides but
      also greatly increases the material variations of solid electrolytes.

PMID- 19856970
TI  - Facile surface functionalization of nanodiamonds.
AB  - Nanodiamonds (NDs) have versatile applications in electro-optical devices,
      sensors, and biomedicine. Owing to the difficulty in activation of the inert
      sp(3) C-H bonds on the surface of NDs, it is not trivial to modify the surface
      functionalities on NDs. A few functionalization methods have been reported in the
      literature for surface modification of NDs. Many of them, however, are either
      multiple steps/time-consuming, or require the use of highly toxic/environmentally
      unfriendly reagents, such as fluorine gas and sulfuric acid. It is necessary to
      develop a simple process for surface functionalization of NDs to have both
      hydrophobic and hydrophilic functional groups. In this report, a facile process
      was developed to allow easy and rapid surface modification of NDs to become
      dispersible in either water or organic solvents using the same process. The
      process involves surface graphitization of NDs, followed by radical initiated
      surface grafting of oligomers with various functionalities, including 
      C(=O)OCH(3), -COOH, -NH(2), or aliphatic moieties.

PMID- 19856971
TI  - Unsymmetrical cruciforms.
AB  - Five new, unsymmetrical 1,4-distyryl-2,5-bisphenylethynylbenzenes (cruciforms,
      XF) have been prepared by a sequential Horner reaction of the bisphosphonate of
      2,5-diiodo-1,4-xylene with two different aromatic aldehydes. The obtained
      diiodide was coupled to phenylacetylene under Sonogashira conditions with
      (Ph(3)P)(2)PdCl(2) as catalyst. The resulting XFs carry dibutylamino, pyridyl,
      cyano, and diphenylamino residues on their styryl arms to give rise to donor-,
      acceptor-, and donor-acceptor-substituted XFs. The optical properties of these
      XFs were investigated. Titration studies using trifluoroacetic acid tracked
      changes in the electronic structure of the XFs upon protonation. Donor XFs
      display a blue shift in absorption and emission upon protonation, while the
      pyridyl-substituted XF displays red shift in absorption and emission upon
      protonation. In the case of the donor-acceptor XF carrying a pyridyl and an
      aminostyryl arm, the first protonation occurs either on the pyridine or on the
      dibutylamino arm; a red shift is seen in absorption (for the former) and a blue
      shift is observed in emission (for the latter). The titration studies indicate
      that the protonated XFs do not display kinetic photoacidity when operating either
      in dichloromethane or acetonitrile solutions. The trends observed for protonation
      were mirrored when the XFs bind to metal cations. While the binding constants of
      the metal cations to the XFs were lower than for that for protons, as in some
      cases full metalation of the XF could not be obtained, the results were
      qualitatively the same. We did not find dynamic excited-state decomplexation
      events in the XFs that we have investigated. The XFs, stilbene derivatives, are
      different from other reported, similarly structured fluorophores as they show
      significant ratiometric changes in emission upon metal complexation; thus,
      distyrylbenzene-derived fluorophores may be, in the end, viable choices as
      platforms for metal ion detection.

PMID- 19856973
TI  - Politics and nanotechnology in the health care industry.

PMID- 19856972
TI  - Duplex formation at the 5' end affects the quadruplex conformation of the human
      telomeric repeat overhang in sodium but not in potassium.
AB  - Human telomeres contain numerous copies of the (TTAGGG)(n).(AATCCC)(n) repeated
      sequence with multiple TTAGGG repeats in 3' single-stranded overhangs. Single
      stranded oligonucleotides consisting of four TTAGGG repeats can fold into various
      intramolecular quadruplex structures stabilized by quartets of guanines. The
      quadruplex structures are believed to play a role in telomere functions and
      considered as targets for anticancer drug design. In an effort to create a more
      realistic model of telomeric DNA, we designed oligonucleotides containing a
      duplex region at the 5' end and four telomeric repeats in the 3' overhang. We
      applied CD spectroscopy and (125)I radioprobing to determine the conformation of
      the quadruplexes formed in the 3' overhangs. We found that in the presence of
      NaCl the conformation of the quadruplex changes with formation of the 5' duplex
      and depends on the position of the interface between the duplex and the 3'
      telomeric sequence. When the duplex region extended to the first T of the first
      TTAGGG repeat, both CD and radioprobing data are consistent with the parallel
      propeller conformation of the overhang. In the presence of KCl, formation of the
      duplex at the 5' end of DNA molecules did not change the fold of the quadruplex
      in the overhang which was interpreted as a mixture of two isomers of 3+1
      conformation regardless of the duplex-overhang interface position. Our results
      demonstrate that the interface between the duplex and single-stranded overhang
      can affect the conformation of the telomeric quadruplex.

PMID- 19856975
TI  - Surface-enhanced Raman spectroscopy and homeland security: a perfect match?
AB  - This Nano Focus article reviews recent developments in surface-enhanced Raman
      spectroscopy (SERS) and its application to homeland security. It is based on
      invited talks given at the "Nanorods and Microparticles for Homeland Security"
      symposium, which was organized by one of the authors and presented at the 238th
      ACS National Meeting and Exhibition in Washington, DC. The three-day symposium
      included approximately 25 experts from academia, industry, and national
      laboratories and included both SERS and non-SERS approaches to detection of
      chemical and biological substances relevant to homeland security, as well as
      fundamental advances. Here, we focus on SERS and how it is uniquely positioned to
      have an impact in a field whose importance is increasing rapidly. We describe
      some technical challenges that remain and offer a glimpse of what form solutions
      might take.

PMID- 19856976
TI  - Pearls of wisdom: stringing nanoparticles and polymers into new assemblies and
      materials.
AB  - From size considerations alone, polymers and nanoparticles should be natural
      partners for the preparation of composite materials. However, this prospect is
      more difficult than first glance would suggest, and clever synthetic, physical,
      and engineering considerations are required to optimize the merged value of
      polymers and nanoparticles. In this issue, Jeffrey Pyun and co-workers provide
      compelling evidence of the value of such composite materials, by stringing
      together magnetic nanoparticles into "pearl necklace" assemblies. In
      instructively interdisciplinary fashion, a full complement of polymer chemistry,
      nanoparticle synthesis, and nanostructural engineering (via solid-phase atomic
      diffusion) are combined to reveal artistically appealing products with novel
      properties that hold promise for the future of energy-storage devices and
      catalytic materials.

PMID- 19856977
TI  - Ubiquitous sensors: when will they be here?
AB  - Chemical and biological sensors are necessary for making continuous measurements
      in a variety of settings. A typical sensor comprises a molecular recognition
      element coupled to a transducer. Binding of the analyte to the recognition
      element leads to signal transduction. Many sensors employ an extrinsic label to
      indirectly signal the presence of the analyte. Label-free methods have the
      advantage that no exogenous reagents are required, making the sensor simple to
      implement. New label-free transduction methods should facilitate the wider
      application of sensors. Challenges remain with reproducibility, calibration, and
      manufacturability. Solving these problems will require an interdisciplinary
      collaboration between chemists, biologists, biochemists, and engineers. An
      article by Sailor and co-workers in this issue takes a significant step toward
      this goal. The availability of inexpensive sensors for wide-scale deployment will
      transform society in terms of health care as well as home and workplace
      monitoring.

PMID- 19856979
TI  - Graphene oxide as an ideal substrate for hydrogen storage.
AB  - Organometallic nanomaterials hold the promise for molecular hydrogen (H(2))
      storage by providing nearly ideal binding strength to H(2) for room-temperature
      applications. Synthesizing such materials, however, faces severe setbacks due to
      the problem of metal clustering. Inspired by a recent experimental breakthrough (
      J. Am. Chem. Soc. 2008 , 130 , 6992 ), which demonstrates enhanced H(2) binding
      in Ti-grafted mesoporous silica, we propose combining the graphene oxide (GO)
      technique with Ti anchoring to overcome the current synthesis bottleneck for
      practical storage materials. Similar to silica, GO contains ample hydroxyl
      groups, which are the active sites for anchoring Ti atoms. GO can be routinely
      synthesized and is much lighter than silica. Hence, higher gravimetric storage
      capacity can be readily achieved. Our first-principles computations suggest that
      GO is primarily made of low-energy oxygen-containing structural motifs on the
      graphene sheet. The Ti atoms bind strongly to the oxygen sites with binding
      energies as high as 450 kJ/mol. This is comparable to that of silica and is
      indeed enough to prevent the Ti atoms from clustering. Each Ti can bind multiple
      H(2) with the desired binding energies (14-41 kJ/mol-H(2)). The estimated
      theoretical gravimetric and volumetric densities are 4.9 wt % and 64 g/L,
      respectively.

PMID- 19856978
TI  - Simultaneous enhancement of photothermal stability and gene delivery efficacy of
      gold nanorods using polyelectrolytes.
AB  - The propensity of nanoparticles to aggregate in aqueous media hinders their
      effective use in biomedical applications. Gold nanorods (GNRs) have been
      investigated as therapeutics, imaging agents, and diagnostics. We report that
      chemically generated gold nanorods rapidly aggregate in biologically relevant
      media. Depositing polyelectrolyte multilayers on gold nanorods enhanced the
      stability of these nanoparticles for at least up to 4 weeks. Dispersions of
      polyelectrolyte (PE)-gold nanorod assemblies (PE-GNRs) demonstrate a stable
      Arrhenius-like photothermal response, which was exploited for the hyperthermic
      ablation of prostate cancer cells in vitro. Subtoxic concentrations of PE-GNR
      assemblies were also employed for delivering exogenous plasmid DNA to prostate
      cancer cells. PE-GNRs based on a cationic polyelectrolyte recently synthesized in
      our laboratory demonstrated higher transfection efficacy and lower cytotoxicity
      compared to those based on polyethyleneimine, a current standard for polymer
      mediated gene delivery. Our results indicate that judicious engineering of
      biocompatible polyelectrolytes leads to multifunctional gold nanorod-based
      assemblies that combine high stability and low cytotoxicity with photothermal
      ablation, gene delivery, and optical imaging capabilities on a single platform.

PMID- 19856980
TI  - Antibunching single-photon emission and blinking suppression of CdSe/ZnS quantum
      dots.
AB  - We demonstrated that by properly coupling to silver nanoprisms, single CdSe/ZnS
      semiconductor quantum dots (QDs) exhibited suppressed blinking behavior, an
      enhanced fluorescence intensity ( approximately 2.5 fold), increased radiative
      decay rates ( approximately 12.5 fold), and antibunching single-photon emission.
      All these modifications significantly promote the overall performance of the
      proposed single-photon sources based on colloidal semiconductor QDs.

PMID- 19856981
TI  - Rotation detection in light-driven nanorotors.
AB  - We analyze the rotational dynamics of light driven nanorotors, made of nanotube
      bundles and gold nanorods aggregates, with nonsymmetric shapes, trapped in
      optical tweezers. We identify two different regimes depending on dimensions and
      optical properties of the nanostructures. These correspond to alignment with
      either the laser propagation axis or the dominant polarization direction, or
      rotational motions caused by either unbalanced radiation pressure or polarization
      torque. By analyzing the motion correlations of the trapped nanostructures, we
      measure with high accuracy both the optical trapping parameters and the rotation
      frequency induced by the radiation pressure. Our results pave the way to improved
      all-optical detection, control over rotating nanomachines, and rotation detection
      in nano-optomechanics.

PMID- 19856982
TI  - Sorted and aligned single-walled carbon nanotube networks for transistor-based
      aqueous chemical sensors.
AB  - Detecting trace amounts of analytes in aqueous systems is important for health
      diagnostics, environmental monitoring, and national security applications. Single
      walled carbon nanotubes (SWNTs) are ideal components for both the sensor material
      and active signal transduction layer because of their excellent electronic
      properties and high aspect ratio consisting of entirely surface atoms.
      Submonolayer arrays, or networks of SWNTs (SWNTnts) are advantageous, and we show
      that topology characteristics of the SWNT network, such as alignment, degree of
      bundling, and chirality enrichment strongly affect the sensor performance. To
      enable this, thin-film transistor (TFT) sensors with SWNTnts were deposited using
      a one-step, low-cost, solution- based method on a polymer dielectric, allowing us
      to achieve stable low-voltage operation under aqueous conditions. These SWNT-TFTs
      were used to detect trace concentrations, down to 2 ppb, of dimethyl
      methylphosphonate (DMMP) and trinitrotoluene (TNT) in aqueous solutions. Along
      with reliable cycling underwater, the TFT sensors fabricated with aligned, sorted
      nanotube networks (enriched with semiconductor SWNTs) showed a higher sensitivity
      to analytes than those fabricated with random, unsorted networks with
      predominantly metallic charge transport.

PMID- 19856983
TI  - Simulating mechanical deformation in nanomaterials with application for energy
      storage in nanoporous architectures.
AB  - Central to porous nanomaterials, with applications spanning catalysts to fuel
      cells is their (perceived) "fragile" structure, which must remain structurally
      intact during application lifespan. Here, we use atomistic simulation to explore
      the mechanical strength of a porous nanomaterial as a first step to
      characterizing the structural durability of nanoporous materials. In particular,
      we simulate the mechanical deformation of mesoporous Li-MnO(2) under stress using
      molecular dynamics simulation. Specifically, such rechargeable Li-ion battery
      materials suffer volume changes during charge/discharge cycles as Li ions are
      repeatedly inserted and extracted from the host beta-MnO(2) causing failure as a
      result of localized stress. However, mesoporous beta-MnO(2) does not suffer
      structural collapse during cycling. To explain this behavior, we generate a full
      atomistic model of mesoporous beta-MnO(2) and simulate localized stress
      associated with charge/discharge cycles. We calculate that mesoporous beta-MnO(2)
      undergoes a volume expansion of about 16% when Li is fully intercalated, which
      can only be sustained without structural collapse, if the nanoarchitecture is
      symmetrically porous, enabling elastic deformation during intercalation.
      Conversely, we predict that unsymmetric materials, such as nanoparticulate beta
      MnO(2), deform plastically, resulting in structural collapse of (Li) storage
      sites and blocked transport pathways; animations revealing elastic and plastic
      deformation mechanisms under mechanical load and crystallization of mesoporous Li
      MnO(2) are presented at the atomistic level.

PMID- 19856985
TI  - 3D Brownian diffusion of submicron-sized particle clusters.
AB  - We report on the translation and rotation of particle clusters made through the
      combination of spherical building blocks. These clusters present ideal model
      systems to study the motion of objects with complex shape. Since they could be
      separated into fractions of well-defined configurations on a sufficient scale and
      because their overall dimensions were below 300 nm, the translational and
      rotational diffusion coefficients of particle doublets, triplets, and
      tetrahedrons could be determined by a combination of polarized dynamic light
      scattering (DLS) and depolarized dynamic light scattering (DDLS). The use of
      colloidal clusters for DDLS experiments overcomes the limitation of earlier
      experiments on the diffusion of complex objects near surfaces because the true 3D
      diffusion can be studied. When the exact geometry of the complex assemblies is
      known, different hydrodynamic models for calculating the diffusion coefficients
      for objects with complex shapes could be applied. Because hydrodynamic friction
      must be restricted to the cluster surface, the so-called shell model, in which
      the surface is represented as a shell of small friction elements, was most
      suitable to describe the dynamics. A quantitative comparison of the predictions
      from theoretical modeling with the results obtained by DDLS showed an excellent
      agreement between experiment and theory.

PMID- 19856984
TI  - Integrated fabrication and magnetic positioning of metallic and polymeric
      nanowires embedded in thin epoxy slabs.
AB  - This paper describes a process for the fabrication and positioning of nanowires
      (of Au, Pd, and conjugated polymers) embedded in thin epoxy slabs. The procedure
      has four steps: (i) coembedding a thin film of metal or conducting polymer with a
      thin film of nickel metal (Ni) in epoxy; (ii) sectioning the embedded structures
      into nanowires with an ultramicrotome ("nanoskiving"); (iii) floating the epoxy
      sections on a pool of water; and (iv) positioning the sections with an external
      magnet to a desired location ("magnetic mooring"). As the water evaporates,
      capillary interactions cause the sections to adhere to the substrate. Both the Ni
      and epoxy can be etched to generate free-standing metallic nanowires. The average
      translational deviation in the positioning of two nanowires with respect to each
      other is 16 +/- 13 mum, and the average angular deviation is 3 +/- 2 degrees .
      Successive depositions of nanowires yield the following structures of interest
      for electronic and photonic applications: electrically continuous junctions of
      two Au nanowires, two Au nanowires spanned by a poly(3-hexylthiophene) (P3HT)
      nanowire; single-crystalline Au nanowires that cross; crossbar arrays of Au
      nanowires; crossbar arrays of Au and Pd nanowires; and a 50 x 50 array of
      poly(benzimidazobenzophenanthroline ladder) (BBL) nanowires. Single-crystalline
      Au nanowires can be placed on glass wool fibers or on microfabricated polymeric
      waveguides, with which the nanowire can be addressed optically.

PMID- 19856986
TI  - Gecko-inspired combined lamellar and nanofibrillar array for adhesion on
      nonplanar surface.
AB  - We report the fabrication from a hard polymer of lamellar structures that act as
      base support planes for high-aspect ratio nanofiber arrays. We experimentally
      show that nanofiber arrays on lamellae can adhere to both planar and nonplanar
      surfaces, exhibiting 5 times greater shear strength on a 100 mum peak-to-peak
      grating than the arrays without the lamellar support structure. The observed
      behavior on nonplanar surfaces is attributed to the high compliance of the
      lamellar flaps. The compliance of the combined lamellae and nanofiber arrays is
      measured to be about 160 times higher than nanofiber arrays on a flat nonlamellar
      backing layer.

PMID- 19856987
TI  - Visualizing systemic clearance and cellular level biodistribution of gold
      nanorods by intrinsic two-photon luminescence.
AB  - Characterization of systemic performance of gold nanostructures is critical to
      the advancement of biomedical applications of these nanomaterials as imaging or
      therapeutic agents. The accuracy of current in vitro methods, however, is limited
      by interanimal variability. We present a novel method capable of monitoring the
      pharmacokinetics of PEGylated gold nanorods (GNRs) in the same animal by using
      intravital two-photon luminescence (TPL) imaging of GNRs flowing through a
      surface blood vessel. The TPL imaging with high speed and submicrometer
      resolution allowed for studying the clearance of GNRs as a function of surface
      coating. PEGylated-GNRs (PEG-NRs) were found to exhibit a biphasic clearance
      mode, with a significantly prolonged blood residence time for branched
      poly(ethylene glycol) (PEG) as compared to the linear PEG. With spectral
      detection to distinguish GNR TPL from tissue autofluorescence, we also mapped the
      cellular distribution of GNRs in the explanted organs, and found most GNRs
      resided in the macrophages in liver and spleen.

PMID- 19856988
TI  - Watching DNA condensation induced by poly(amido amine) dendrimers with time
      resolved cryo-TEM.
AB  - The condensation of DNA by poly(amido amine) dendrimers of generation 1, 2, and 4
      has been followed by time-resolved cryogenic transmission electron microscopy
      (cryo-TEM). The recorded images show that significant morphological rearrangement
      occurs for DNA condensed with the lower generation dendrimers leading to the
      formation of toroidal aggregates. Higher charge density dendrimers, on the other
      hand, give rise to globular aggregates, where no transient morphologies are
      observed. We suggest that the dendrimers in this case are kinetically trapped as
      soon as they bind to the DNA strand.

PMID- 19856989
TI  - The isotropic-nematic interface in suspensions of Na-fluorohectorite synthetic
      clay.
AB  - Colloidal suspensions of Na-fluorohectorite synthetic clay platelets in saline
      water exhibit coexisting isotropic and nematic phases, due to gravitational
      separation of the polydisperse particles. We study the ordering of the platelets
      at the interfaces between various coexisting phases. Four different experimental
      techniques are employed: visual observation of birefringence, synchrotron wide
      angle and small-angle X-ray scattering, and magnetic resonance imaging. We find
      that at the narrow isotropic sol-nematic sol interface the platelets are lying
      horizontally, i.e. with their mean platelet normal along the vertical direction.
      The experiments indicate that the platelets align homeotropically both at the
      isotropic sol-nematic sol interface and at the nematic sol-wall interface. We
      further investigate the complex alignment effect of a horizontally applied
      magnetic field in the nematic sol, and we compare it with the adjacent nematic
      gel.

PMID- 19856990
TI  - Catanionic micelles as a model to mimic biological membranes in the presence of
      anesthetic alcohols.
AB  - We show here the influence of n-alcohols (C(2)OH-C(8)OH) on the solubility
      behavior of cationic-anionic surfactant mixtures, so-called "catanionics". We
      studied catanionics of different compositions composed of sodium dodecyl sulfate
      (SDS)/cetyltrimethylammonium bromide (CTAB) and sodium dodecanoate (SDod)/CTAB
      mixtures. Interestingly, with a molar excess of SDS, long chain n-alcohols
      (C(4)OH-C(8)OH) significantly depress the solubility temperature of the SDS+CTAB
      catanionic and increase the kinetic stability of the solution. The visual
      observations of solubility temperatures of catanionics were further confirmed by
      differential scanning calorimetry (DSC) measurements. For the catanionics a
      multistep solubilization was observed by DSC, for which the sulfate headgroup is
      responsible. This was probed by replacing SDS by SDod. A remarkable analogy was
      found between the influence of the alcohols on the solubility patterns of the
      catanionic mixtures and on the anesthesia of tadpoles. Possible reasons for this
      analogy are discussed also in this paper.

PMID- 19856991
TI  - Line-on-line organic-organic heteroepitaxy of quaterrylene on hexa-peri
      hexabenzocoronene on Au(111).
AB  - In a recent paper, we discussed the optical properties of a heterostructure
      consisting of a highly ordered monolayer of quaterrylene (QT), electronically
      decoupled from the gold substrate by a predeposited epitaxial monolayer of hexa
      peri-hexabenzocoronene (HBC). Here we now present the detailed structural
      investigation of this organic double-layer system. We show that the structure of
      the heterosystem can be identified as line-on-line coincidence (lol), a new type
      of epitaxy discovered by us previously for the system 3,4,9,10
      perylenetetracarboxylic dianhydride (PTCDA) on HBC on highly oriented pyrolytic
      graphite (HOPG). Additionally, we provide evidence on the basis of advanced
      potential energy calculations that indeed energetic gain drives this lol growth
      mode.

PMID- 19856992
TI  - Curvature-tuned preparation of nanoliposomes.
AB  - Numerous methods have been reported for the preparation of liposomes, many of
      which, in addition to requiring time-consuming preparative steps and the use of
      organic solvents, result in heterogeneous liposome populations of incontrollable
      size. Taking into consideration the phenomenon of spontaneous vesiculation and
      the theory of curvature, here we present an extremely rapid and simple, solvent
      free method for the preparation of monodisperse solutions of highly stable small
      unilamellar vesicles using both charged and zwitterionic lipids mixed with lyso
      palmitoylphosphatidylcholine, exploiting a combination of a rapid pH change
      followed by a defined period of equilibration. Various experimental parameters
      and their interactions were evaluated in terms of their effect on resulting
      liposome size and shape, as well as on liposome stability and size distribution,
      with transmission electron microscope imaging being used to visualize the formed
      liposomes, and photon correlation spectroscopy to obtain statistical data on mean
      diameter and monodispersity of the liposome population. zeta potential
      measurements also provided information about the interpretation of vesiculation
      kinetics and liposome stability. The time interval of pH jump, operation
      temperature, equilibration time, and lipid type were shown to be the determining
      factors controlling the size, shape, and monodispersity of the liposomes. Buffer
      type was also found to be important for the long-term storage of the liposomes.
      Ongoing work is looking at the application of the developed method for
      encapsulation of bioactive molecules, such as drugs, genetic materials, and
      enzymes.

PMID- 19856993
TI  - Protein-solid interactions: important role of solvent, ions, temperature, and
      buffer in protein binding to alpha-Zr(IV) phosphate.
AB  - The interaction of proteins with a solid surface involves a complex set of
      interactions, and elucidating the details of these interactions is essential in
      the rational design of solid surfaces for applications in biosensors,
      biocatalysis, and biomedical applications. We examined the enthalpy changes
      accompanying the binding of met-hemoglobin, met-myoglobin, and lysozyme to
      layered alpha-Zr(IV)phosphate (20 mM NaPipes, 1 mM TBA, pH 7.2, 298 K) by
      titration calorimetry, under specific conditions. The corresponding binding
      enthalpies for the three proteins are -24.2 +/- 2.2, -10.6 +/- 2, and 6.2 +/- 0.2
      kcal/mol, respectively. The binding enthalpy depended on the charge of the
      protein where the binding of positively charged proteins to the negatively
      charged solid surface was endothermic while the binding of negatively charged
      proteins to the negatively charged solid was exothermic. These observations are
      contrary to a simple electrostatic model where binding to the oppositely charged
      surface is expected to be exothermic. The binding enthalpy depended on the net
      charge on the protein, ionic strength of the medium, the type of buffer ions
      present, and temperature. The temperature dependence studies of binding
      enthalpies resulted in the estimation of heat capacity changes accompanying the
      binding. The heat capacity changes observed with Hb, Mb, and lysozyme are 1.4 +/-
      0.3, 0.89 +/- 0.2, and 0.74 +/- 0.1 kcal/(mol.K), respectively, and these values
      depended on the net charge of the protein. The enthalpy changes also depended
      linearly on the enthalpy of ionization of the buffer, and the numbers of protons
      released per protein estimated from this data are 12.6 +/- 2, 6.0 +/- 1.2, and
      1.2 +/- 0.5 for Hb, Mb, and lysozyme, respectively. Binding enthalpies,
      independent of buffer ionization, are also estimated from these data. Entropy
      changes are related to the loss in the degrees of freedom when the protein binds
      to the solid and the displacement of solvent molecules/protons/ions from the
      protein-solid interface. Proton coupled protein binding is one of the major
      processes in these systems, which is novel, and the binding enthalpies can be
      predicted from the net charge of the protein, enthalpy of buffer ionization,
      ionic strength, and temperature.

PMID- 19856994
TI  - Organic solvent-dispersed TiO(2) nanoparticle characterization.
AB  - Anatase titanium dioxide nanoparticles are derivatized with the polymerizable
      reagent (3-methacryloxypropyl)trimethoxysilane to provide dispersions in organic
      solvent. The titania core particles are characterized by transmission electron
      microscopy (TEM) and X-ray diffraction (XRD). The organic component structures
      and thickness are elucidated using nuclear magnetic resonance (NMR), quasielastic
      light scattering (QELS), and size-exclusion chromatography (SEC). Thin, high
      refractive-index coatings prepared from the organic dispersions are characterized
      by atomic force microscopy (AFM). The combination of microscopies, spectroscopy,
      light scattering, and separation techniques provides unique information on the
      structure, thickness, morphology, and size distributions of the surface-treated
      nanoparticles that is difficult to obtain by any single technique. The findings
      indicate titania platelets with a modal diameter of 9.8 nm and a thickness of
      approximately 1.5 nm. The particles are coated with a 1.5-1.9 nm thick organic
      ligand layer, and a substantial population of 2 nm siloxane oligomers is
      detected. The analytical methodology presented may also be useful for
      characterizing other anisotropic organic-inorganic nanoparticles and their
      dispersions.

PMID- 19856995
TI  - Kinetics of lithium ion transfer at the interface between graphite and liquid
      electrolytes: effects of solvent and surface film.
AB  - The kinetics of lithium ion transfer at an interface between graphite and liquid
      electrolyte was studied by ac impedance spectroscopy. Using highly oriented
      pyrolytic graphite (HOPG) as a model electrode, we evaluated the activation
      energies of the interfacial lithium ion transfer from the temperature dependences
      of the interfacial conductivities. When a binary electrolyte consisting of
      LiClO(4) dissolved in a mixture of ethylene carbonate (EC) and dimethyl carbonate
      (DMC) (1:1 by volume) was used, the activation energy of the interfacial lithium
      ion transfer was 58 kJ mol(-1), while an electrolyte consisting of LiClO(4)
      dissolved in DMC gave an activation energy of 40 kJ mol(-1). A calculation with
      the density functional theory clarified that the solvation ability of EC is
      higher than that of DMC. Therefore, we concluded that the activation energies of
      the interfacial lithium ion transfer at graphite reflected the energies for the
      desolvation of lithium ion from the solvent molecule. Furthermore, the activation
      energies of the interfacial lithium ion transfer varied in the presence of
      different surface films (solid electrolyte interphase, SEI). These results
      suggest that the kinetics of the interfacial lithium ion transfer at graphite is
      influenced by the compositions of SEI films as well as the desolvation of lithium
      ion from solvent molecules.

PMID- 19856997
TI  - Comment on particle tracking model for colloid transport near planar surfaces
      covered with spherical asperities.

PMID- 19856996
TI  - Patterning discrete stem cell culture environments via localized self-assembled
      monolayer replacement.
AB  - Self-assembled monolayers (SAMs) of alkanethiolates on gold have become an
      important tool for probing cell-material interactions. Emerging studies in stem
      cell biology are particularly reliant on well-defined model substrates, and
      rapid, highly controllable fabrication methods may be necessary for
      characterizing the wide array of stem cell-material interactions. Therefore, this
      study describes a rapid method for creating SAM cell culture substrates with
      multiple discrete regions of controlled peptide identity and density. The
      approach uses a NaBH(4) solution to selectively remove regions of bioinert,
      hydroxyl-terminated oligo(ethylene glycol) alkanethiolate SAM and then locally
      replace them with mixed SAMs of hydroxyl- and carboxylic acid-terminated
      oligo(ethylene glycol) alkanethiolates. The cell adhesion peptide Arg-Gly-Asp-Ser
      Pro (RGDSP) was then covalently linked to carboxylic acid-terminated mixed SAM
      regions to create cell adhesive environments within a bioinert background. SAM
      preparation and peptide immobilization were characterized using polarization
      modulation-infrared reflection-absorption spectroscopy (PM-IRRAS), as well as
      assays to monitor conjugation of a fluorescently labeled peptide. This "localized
      SAM replacement" method was achieved using an array of microchannels, which
      facilitated rapid and simple processing. Results indicate that immobilized RGDSP
      promoted spatially localized attachment of human mesenchymal stem cells (hMSCs)
      within specified regions, while maintaining a stable, bioinert background in
      serum-containing cell culture conditions for up to 14 days. Cell attachment to
      patterned regions presenting a range of cell adhesion peptide densities
      demonstrated that peptide identity and density strongly influence hMSC spreading
      and focal adhesion density. These substrates contain discrete, well-defined
      microenvironments for stem cell culture, which could ultimately enable high
      throughput screening for the effects of immobilized signals on stem cell
      phenotype.

PMID- 19856998
TI  - Liquid chromatography-tandem and MALDI imaging mass spectrometry analyses of
      RCL2/CS100-fixed, paraffin-embedded tissues: proteomics evaluation of an
      alternate fixative for biomarker discovery.
AB  - Human tissues are an important source of biological material for the discovery of
      novel biomarkers. Fresh-frozen tissue could represent an ideal supply of archival
      material for molecular investigations. However, immediate flash freezing is
      usually not possible, especially for rare or valuable tissue samples such as
      biopsies. Here, we investigated the compatibility of RCL2/CS100, a non-cross
      linking, nontoxic, and nonvolatile organic fixative, with shotgun proteomic
      analyses. Several protein extraction protocols compatible with mass spectrometry
      were investigated from RCL2/CS100-fixed and fresh-frozen colonic mucosa, breast,
      and prostate tissues. The peptides and proteins identified from RCL2/CS100 tissue
      were then comprehensively compared with those identified from matched fresh
      frozen tissues using a bottom-up strategy based on nano-reversed phase liquid
      chromatography coupled with tandem mass spectrometry (nanoRPLC-MS/MS). Results
      showed that similar peptides could be identified in both archival conditions and
      the proteome coverage was not obviously compromised by the RCL2/CS100 fixation
      process. NanoRPLC-MS/MS of laser capture microdissected RCL2/CS100-fixed tissues
      gave the same amount of biological information as that recovered from whole
      RCL2/CS100-fixed or frozen tissues. We next performed MALDI tissue profiling and
      imaging mass spectrometry and observed a high level of agreement in protein
      expression as well as excellent agreement between the images obtained from
      RCL2/CS100-fixed and fresh-frozen tissue samples. These results suggest that
      RCL2/CS100-fixed tissues are suitable for shotgun proteomic analyses and tissue
      imaging. More importantly, this alternate fixative opens the door to the analysis
      of small, valuable, and rare target lesions that are usually inaccessible to
      complementary biomarker-driven genomic and proteomic research.

PMID- 19856999
TI  - Affirmed yet unaware: exploring the role of awareness in the process of self
      affirmation.
AB  - Three studies investigated whether self-affirmation can proceed without
      awareness, whether people are aware of the influence of experimental self
      affirmations, and whether such awareness facilitates or undermines the self
      affirmation process. The authors found that self-affirmation effects could
      proceed without awareness, as implicit self-affirming primes (utilizing sentence
      unscrambling procedures) produced standard self-affirmation effects (Studies 1
      and 3). People were generally unaware of self-affirmation's influence, and self
      reported awareness was associated with decreased impact of the affirmation
      (Studies 1 and 2). Finally, affirmation effects were attenuated when people
      learned that self-affirmation was designed to boost self-esteem (Study 2) or told
      of a potential link between self-affirmation and evaluations of threatening
      information (Study 3). Together, these studies suggest not only that affirmation
      processes can proceed without awareness but also that increased awareness of the
      affirmation may diminish its impact.

PMID- 19857000
TI  - The existence bias.
AB  - The authors demonstrate that people treat the mere existence of something as
      evidence of its goodness. Studies 1 and 2 demonstrate that an existing state is
      evaluated more favorably than an alternative. Study 3 shows that imagining an
      event increases estimates of its likelihood, which in turn leads to favorable
      evaluation; the more likely that something will be, the more positively it is
      evaluated. Study 4 shows that the more a form is described as prevalent, the more
      aesthetically attractive is that form. This indicates a causal relationship
      between aesthetic judgments and existence in a domain lacking choice among
      alternatives. Study 5 extends the existence bias to gustatory evaluation and
      demonstrates that the effect is not moderated by valence. Together these studies
      suggest that mere existence leads to assumptions of goodness; the status quo is
      seen as good, right, attractive, tasty, and desirable.

PMID- 19857001
TI  - When the association between appearance and outcome contaminates social judgment:
      a bidirectional model linking group homogeneity and collective treatment.
AB  - Group formation is an inevitable consequence of social life, and the tendency to
      perceive people as a collective unit persists once they have been categorized as
      a group. Drawing on the concept of homogeneity, the authors propose a model
      suggesting that groups may endure in part because people who are perceived as
      homogeneous attract collective treatment (e.g., monetary rewards and punishment),
      and such treatment further reinforces the perception that the group's members are
      homogeneous. In support of this model, more homogeneous groups attracted
      collective treatment and collectively treated groups seemed to be more
      homogeneous thereafter. The authors suggest that these effects arise in part
      because people intuitively believe that group homogeneity is associated with
      collective treatment, and they present evidence suggesting that this applies to
      at least one policy-relevant real-world setting.

PMID- 19857002
TI  - Self-centered social exchange: differential use of costs versus benefits in
      prosocial reciprocity.
AB  - Maintaining equitable social relations often requires reciprocating "in kind" for
      others' prosocial favors. Such in-kind reciprocity requires assessing the value
      of a prosocial action, an assessment that can lead to egocentric biases in
      perceived value between favor givers versus favor receivers. In any prosocial
      exchange, 1 person (the giver) incurs a cost to provide a benefit for another
      person (the receiver). Six experiments suggest that givers may attend more to the
      costs they incur in performing a prosocial act than do receivers, who tend to
      focus relatively more on the benefits they receive. Givers may therefore expect
      to be reciprocated on the basis of the costs they incur, whereas receivers
      actually reciprocate primarily on the basis of the benefit they receive. This
      research identifies 1 challenge to maintaining a sense of equity in social
      relations and predicts when people are likely to feel fairly versus unfairly
      valued in their relationships.

PMID- 19857003
TI  - Seeking conversion versus advocating tolerance in the pursuit of social change.
AB  - In 2 studies, the authors examined reactions to social change effected by
      minorities' successful increase of tolerance for diversity within a group or
      conversion of a group to the minority position. Minorities who increased
      tolerance for diversity, compared with those who converted a group to their own
      position, identified more strongly with the group (Study 1). Study 2 replicated
      these findings. Additionally, it showed that majorities disidentified less from
      the group when majorities lost their dominant position due to the group's
      increased tolerance for diversity than when majorities lost their dominant
      position due to the group's conversion to the minority position. Thus, minority
      effected social change left a group stronger when that change increased the
      group's tolerance than when the group experienced conversion. Expectations that
      differences within a group would be regulated through social conflict (vs.
      conciliation) mediated the effect of the mode of change on group identification.
      Motives for minorities' pursuit of social change through tolerance of diversity
      versus group conversion are discussed.

PMID- 19857004
TI  - Defensive helping: threat to group identity, ingroup identification, status
      stability, and common group identity as determinants of intergroup help-giving.
AB  - On the basis of development of the concept of "defensive helping," the authors
      demonstrated that high ingroup identifiers thwart a threat to group identity
      through defensive help-giving (i.e., by extending help to an outgroup member
      whose achievements jeopardize their status). Participants were 255 Israeli high
      school students (130 boys and 125 girls) ages 16-18. The phenomenon of defensive
      helping was demonstrated in a minimal group (Study 1) and real-group (Study 2)
      experiment. Study 3, which examined real groups, supported the extension of the
      phenomenon of defensive helping to relations between high- and low-status groups,
      showing that members of a high-status group who perceive status relations with
      the low-status outgroup as unstable will protect the ingroup's identity by
      providing dependency-oriented help to the low-status outgroup. Priming for common
      ingroup identity reversed this pattern, with participants electing to offer
      autonomy-oriented rather than defensive help. Theoretical and applied
      implications of these findings are discussed with respect to social change,
      paternalism, and helping between nations.

PMID- 19857005
TI  - Give a person power and he or she will show interpersonal sensitivity: the
      phenomenon and its why and when.
AB  - The goal of the present research was to investigate whether high or low power
      leads to more interpersonal sensitivity and what potentially mediates and
      moderates this effect. In Study 1, 76 participants in either a high- or low-power
      position interacted; in Study 2, 134 participants were implicitly primed with
      either high- or low-power or neutral words; and in Study 3, 96 participants were
      asked to remember a situation in which they felt high or low power (plus a
      control condition). In Study 4, 157 participants were told to identify with
      either an egoistic, empathic, or neutral leadership style. In all studies,
      interpersonal sensitivity, defined as correctly assessing other people, was then
      measured using different instruments in each study. Consistently, high power
      resulted in more interpersonal sensitivity than low power. Feeling respected and
      proud was partially responsible for this effect. Empathic power as a personality
      trait was related to more interpersonal sensitivity, and high-power individuals
      who adopted an empathic instead of an egoistic leadership style were more
      interpersonally sensitive.

PMID- 19857006
TI  - The cultural effects of job mobility and the belief in a fixed world: evidence
      from performance forecast.
AB  - Results from 5 studies illustrate how perception of and experiences with low job
      mobility can shape culture-characteristic pattern of judgments and behaviors.
      Although both Americans and some Asian groups (e.g., Chinese, Asian Americans)
      consider having successful practitioners' personality traits (role personalities)
      to be important to job performance, the Asian groups place heavier emphasis on
      possessing role personalities when making performance forecast than do Americans
      (Studies 1-3). Moreover, even among Americans, a brief subjective experience with
      low job mobility can increase the perceived importance of possessing role
      personalities in performance forecast (Study 4), and a brief direct experience
      with low job mobility can increase job applicants' tendency to claim possession
      of role personality traits in job applications (Study 5). Furthermore, the belief
      in a fixed world mediates the relationship between perception of low job mobility
      and perceived importance of possessing role personalities in performance forecast
      (Study 2).

PMID- 19857007
TI  - Does devoutness delay death? Psychological investment in religion and its
      association with longevity in the Terman sample.
AB  - Religious people tend to live slightly longer lives (M. E. McCullough, W. T.
      Hoyt, D. B. Larson, H. G. Koenig, & C. E. Thoresen, 2000). On the basis of the
      principle of social investment (J. Lodi-Smith & B. W. Roberts, 2007), the authors
      sought to clarify this phenomenon with a study of religion and longevity that (a)
      incorporated measures of psychological religious commitment; (b) considered
      religious change over the life course; and (c) examined 19 measures of
      personality traits, social ties, health behaviors, and mental and physical health
      that might help to explain the religion-longevity association. Discrete-time
      survival growth mixture models revealed that women (but not men) with the lowest
      degrees of religiousness through adulthood had shorter lives than did women who
      were more religious. Survival differences were largely attributable to cross
      sectional and prospective between-class differences in personality traits, social
      ties, health behaviors, and mental and physical health.

PMID- 19857009
TI  - Predicting unpredictability: do measures of interpersonal rigidity/flexibility
      and distress predict intraindividual variability in social perceptions and
      behavior?
AB  - Maladjusted individuals have been theorized to exhibit problematic
      intraindividual variability of social behavior across situations. This
      variability is either excessively high (i.e., unpredictable) or low (i.e.,
      rigid), or the behavior is inappropriately matched to the interpersonal context
      (noncomplementary). However, research has not tested systematically whether
      interpersonal distress and purported measures of rigidity actually predict these
      different types of variability across a broad range of social situations.
      Participants completed measures of interpersonal functioning and then responded
      to a range of hypothetical interpersonal scenarios, rating perceptions of others
      and their own expected behavioral responses (Study 1). A subset of participants
      also rated others' and their own social behaviors across a week of naturalistic
      social interactions (Study 2). Results most consistently suggested that
      interpersonal distress predicts high intraindividual variability, with little
      support for the measurement or theory of rigidity. Moreover, variability of
      social perceptions partially mediated the link between distress and behavioral
      variability. Results largely persisted even after accounting for gender and
      variables' mean levels, and cannot be fully explained by interpersonal
      complementarity. The implications of these dynamic processes for understanding
      personality and interpersonal adjustment are discussed.

PMID- 19857008
TI  - Intellect as distinct from Openness: differences revealed by fMRI of working
      memory.
AB  - Relatively little is known about the neural bases of the Big Five personality
      trait Openness/Intellect. This trait is composed of 2 related but separable
      aspects, Openness to Experience and Intellect. On the basis of previous
      behavioral research (C. G. DeYoung, J. B. Peterson, & D. M. Higgins, 2005), the
      authors hypothesized that brain activity supporting working memory (WM) would be
      related to Intellect but not to Openness. To test this hypothesis, the authors
      used functional magnetic resonance imaging (fMRI) to scan a sample of 104 healthy
      adults as they performed a difficult WM task. Intellect (and not Openness) was
      found to correlate with WM accuracy and with accuracy-related brain activity, in
      left lateral anterior prefrontal cortex and posterior medial frontal cortex.
      Neural activity in these regions mediated the association between Intellect and
      WM performance, implicating these regions in the neural substrate of Intellect.
      Intellect was also correlated significantly with scores on tests of intelligence
      and WM capacity, but the association of Intellect with brain activity could not
      be entirely explained by cognitive ability.

PMID- 19857010
TI  - The structure of intraindividual value change.
AB  - Values are assumed to be relatively stable during adulthood. Yet, little research
      has examined value stability and change, and there are no studies on the
      structure of value change. On the basis of S. H. Schwartz's (1992) value theory,
      the authors propose that the structure of intraindividual value change mirrors
      the circumplexlike structure of values so that conflicting values change in
      opposite directions and compatible values change in the same direction. Four
      longitudinal studies, varying in life contexts, time gaps, populations,
      countries, languages, and value measures, supported the proposed structure of
      intraindividual value change. An increase in the importance of any one value is
      accompanied by slight increases in the importance of compatible values and by
      decreases in the importance of conflicting values. Thus, intraindividual changes
      in values are not chaotic, but occur in a way that maintains Schwartz's value
      structure. Furthermore, the greater the extent of life-changing events, the
      greater the value change found, whereas age was only a marginal negative
      predictor of value change when life events were taken into account. Implications
      for the structure of personality change are discussed.

PMID- 19857011
TI  - All letters are not equal: subgraphemic texture in orthographic working memory.
AB  - A central issue in the study of reading and spelling has been to understand how
      the consistency or frequency of letter-sound relationships affects written
      language processing. We present, for the first time, evidence that the sound
      spelling frequency of subgraphemic elements of words (letters within digraphs)
      contributes to the accuracy with which these letters are produced in spelling. We
      report findings from 2 studies that demonstrate that letters within digraphs
      display differential susceptibility to error under conditions of disruption to
      orthographic working memory (O-WM). In the 1st, O-WM was disrupted as a result of
      neurological damage; in the 2nd, O-WM disruption was produced in neurologically
      intact, skilled spellers under dual task conditions with a shadowing task carried
      out during spelling. In both studies, segments with low versus high levels of
      sound-letter convergence, a measure of the frequency of sublexical mappings, were
      more vulnerable to disruption even when factors such as letter position,
      consonant-vowel context, and phoneme-to-grapheme mapping probability of the
      digraphs were controlled. These results contribute to our understanding of the
      internal texture of orthographic representations, providing evidence that
      individual letters differ in their activation strength and, as a result, in their
      susceptibility to error.

PMID- 19857012
TI  - Attentional modulation of the mere exposure effect.
AB  - The mere exposure effect refers to the phenomenon where previous exposures to
      stimuli increase participants' subsequent affective preference for those stimuli.
      This study explored the effect of selective attention on the mere exposure
      effect. The experiments manipulated the to-be-attended drawings in the exposure
      period (either red or green polygons in Experiments 1 and 2; both red and green
      polygons in Experiments 3 and 4) and black to-be-evaluated drawings in the
      affective judgment period (morphologically identical to the red or green polygons
      in Experiments 1 and 4; morphologically identical to the composite drawings in
      Experiments 2 and 3). The results showed a significant mere exposure effect only
      for the target shapes involved in attentional selection, even when the
      participants could recognize the nontarget shapes. This indicates that selective
      attention modulated the mere exposure effect.

PMID- 19857013
TI  - Perceptual-gestural (mis)mapping in serial short-term memory: the impact of
      talker variability.
AB  - The mechanisms underlying the poorer serial recall of talker-variable lists
      (e.g., alternating female-male voices) as compared with single-voice lists were
      examined. We tested the novel hypothesis that this talker variability effect
      arises from the tendency for perceptual organization to partition the list into
      streams based on voice such that the representation of order maps poorly onto the
      formation of a gestural sequence-output plan assembled in support of the
      reproduction of the true temporal order of the items. In line with the
      hypothesis, (a) the presence of a spoken lead-in designed to further promote by
      voice perceptual partitioning accentuates the effect (Experiments 1 and 2); (b)
      the impairment is larger the greater the acoustic coherence is between
      nonadjacent items: Alternating-voice lists are more poorly recalled than four
      voice lists (Experiment 3); and (c) talker variability combines nonadditively
      with phonological similarity, consistent with the view that both variables
      disrupt sequence output planning (Experiment 4). The results support the view
      that serial short-term memory performance reflects the action of sequencing
      processes embodied within general-purpose perceptual input-processing and
      gestural output-planning systems.

PMID- 19857014
TI  - Superior self-paced memorization of digits in spite of a normal digit span: the
      structure of a memorist's skill.
AB  - Over the last century many individuals with exceptional memory have been studied
      and tested in the laboratory. This article studies Chao Lu, who set a Guinness
      World Record by memorizing 67,890 decimals of pi. Chao Lu's superior self-paced
      memorization of digits is shown through analyses of study times and verbal
      reports to be mediated by mnemonic encoding and retrieval processes. Furthermore,
      Chao Lu's development of his superior memory for decimals of pi is consistent
      with his engagement in thousands of hours of memorization. In contrast to most
      other studied memorists, who have digit spans over 15 digits, Chao Lu exhibited a
      digit span in only the normal range. Implications for different types of
      memorization skills and associated practice activities are discussed.

PMID- 19857015
TI  - Distractor modality can turn semantic interference into semantic facilitation in
      the picture-word interference task: implications for theories of lexical access
      in speech production.
AB  - A number of recent studies have questioned the idea that lexical selection during
      speech production is a competitive process. One type of evidence against
      selection by competition is the observation that in the picture-word interference
      task semantically related distractors may facilitate the naming of a picture,
      whereas the selection by competition account predicts them to interfere. In the
      experiments reported in this article, the authors systematically varied, for a
      given type of semantic relation-that is, basic-level distractors (e.g., fish)
      during subordinate-level naming (e.g., carp)-the modality in which distractor
      words were presented (auditory vs. visual) and the proportion of response
      congruent trials (i.e., trials allowing for the correct naming response to be
      derived from both the distractor and the target). With auditory distractors,
      semantic interference was obtained irrespective of the proportion of response
      congruent trials (low in Experiment 1, high in Experiment 2). With visual
      distractors, no semantic effect was obtained with a low proportion of response
      congruent trials (Experiment 3), whereas a semantic facilitation effect was
      obtained with a high proportion of response-congruent trials (Experiment 4). The
      authors propose that two processes contribute to semantic effects observed in the
      picture-word interference paradigm, namely selection by competition (leading to
      interference) and response congruency (leading to facilitation). Whether
      facilitation due to response congruency overrules the interference effect because
      of competition depends on the relative strength of these two processes.

PMID- 19857016
TI  - Thematic relations affect similarity via commonalities.
AB  - Thematic relations are an important source of perceived similarity. For instance,
      the rowing theme of boats and oars increases their perceived similarity. The
      mechanism of this effect, however, has not been specified previously. The authors
      investigated whether thematic relations affect similarity by increasing
      commonalities or by decreasing differences. In Experiment 1, thematic relations
      affected similarity more than difference, thereby producing a noninversion of
      similarity and difference. Experiment 2 revealed substantial individual
      variability in the preference for thematic relations and, consequently, in the
      noninversion of ratings. In sum, the experiments demonstrated a noninversion of
      similarity and difference that was caused by thematic relations and exhibited
      primarily by a subgroup of participants. These results indicate that thematic
      relations affect perceived similarity by increasing the contribution of
      commonalities rather than by decreasing the contribution of differences.

PMID- 19857017
TI  - Cultural differences in complex addition: efficient Chinese versus adaptive
      Belgians and Canadians.
AB  - In the present study, the authors tested the effects of working-memory load on
      math problem solving in 3 different cultures: Flemish-speaking Belgians, English
      speaking Canadians, and Chinese-speaking Chinese currently living in Canada.
      Participants solved complex addition problems (e.g., 58 + 76) in no-load and
      working-memory load conditions, in which either the central executive or the
      phonological loop was loaded. The authors used the choice/no-choice method to
      obtain unbiased measures of strategy selection and strategy efficiency. The
      Chinese participants were faster than the Belgians, who were faster and more
      accurate than the Canadians. The Chinese also required fewer working-memory
      resources than did the Belgians and Canadians. However, the Chinese chose less
      adaptively from the available strategies than did the Belgians and Canadians.
      These cultural differences in math problem solving are likely the result of
      different instructional approaches during elementary school (practice and
      training in Asian countries vs. exploration and flexibility in non-Asian
      countries), differences in the number language, and informal cultural norms and
      standards. The relevance of being adaptive is discussed as well as the
      implications of the results in regards to the strategy choice and discovery
      simulation model of strategy selection (J. Shrager & R. S. Siegler, 1998).

PMID- 19857018
TI  - Congruity effects between materials and processing tasks in the survival
      processing paradigm.
AB  - Nairne, Thompson, and Pandeirada (2007) reported a series of experiments in which
      processing unrelated words in terms of their relevance to a grasslands survival
      scenario led to better retention relative to other semantic processing tasks. The
      impetus for their study was the premise that human memory systems evolved under
      the selection pressures of our ancestral past. In 3 experiments, we extended this
      functional approach to investigate the congruity effect-the common finding that
      people remember items better if those items are congruent with the way in which
      they are processed. Experiment 1 was a replication of Nairne et al.'s (2007)
      experiment and showed congruity effects in the survival processing paradigm. To
      avoid potential item-selection artifacts from randomly selected words, we
      manipulated congruence between words and processing condition in Experiments 2
      and 3. As expected, final recall was highest when the type of processing and the
      materials were congruent, indicating that people remember stimuli better if the
      stimuli are congruent with the goals associated with their processing. However,
      contrary to our predictions, no survival processing advantage emerged between the
      2 congruent conditions or for a list of irrelevant words. When congruity was
      controlled in a mixed list design, the survival processing advantage disappeared.

PMID- 19857019
TI  - Exaggerated risk: prospect theory and probability weighting in risky choice.
AB  - In 5 experiments, we studied precautionary decisions in which participants
      decided whether or not to buy insurance with specified cost against an
      undesirable event with specified probability and cost. We compared the risks
      taken for precautionary decisions with those taken for equivalent monetary
      gambles. Fitting these data to Tversky and Kahneman's (1992) prospect theory, we
      found that the weighting function required to model precautionary decisions
      differed from that required for monetary gambles. This result indicates a failure
      of the descriptive invariance axiom of expected utility theory. For precautionary
      decisions, people overweighted small, medium-sized, and moderately large
      probabilities-they exaggerated risks. This effect is not anticipated by prospect
      theory or experience-based decision research (Hertwig, Barron, Weber, & Erev,
      2004). We found evidence that exaggerated risk is caused by the accessibility of
      events in memory: The weighting function varies as a function of the
      accessibility of events. This suggests that people's experiences of events leak
      into decisions even when risk information is explicitly provided. Our findings
      highlight a need to investigate how variation in decision content produces
      variation in preferences for risk.

PMID- 19857020
TI  - Transfer of magnitude and spatial mappings to the SNARC effect for parity
      judgments.
AB  - Left-right keypresses to numerals are faster for pairings of small numbers to
      left response and large numbers to right response than for the opposite pairings.
      This spatial numerical association of response codes (SNARC) effect has been
      attributed to numbers being represented on a mental number line. We examined this
      issue in 3 experiments using a transfer paradigm. Participants practiced a number
      magnitude-judgment task or spatial stimulus-response compatibility task with
      parallel or orthogonal stimulus-response dimensions prior to performing a parity
      judgment task. The SNARC effect was enhanced following a small-left/large-right
      magnitude mapping but reversed following a small-right/large-left mapping,
      indicating that associations between magnitude and response defined for the
      magnitude-judgment task were maintained for the parity-judgment task. The SNARC
      effect was unaffected by practice with compatible or incompatible spatial mapping
      for the parallel spatial task but was larger following up-right/down-left mapping
      than up-left/down-right mapping for the orthogonal spatial task. These results
      are inconsistent with the SNARC effect being due to a horizontal number line
      representation but consistent with a view that correspondence of stimulus and
      response code polarities contributes to the effect.

PMID- 19857021
TI  - Generation and perceptual implicit memory: different generation tasks produce
      different effects on perceptual priming.
AB  - The generation manipulation has been critical in delineating differences between
      implicit and explicit memory. In contrast to past research, the present
      experiments indicate that generating from a rhyme cue produces as much perceptual
      priming as does reading. This is demonstrated for 3 visual priming tasks:
      perceptual identification, word-fragment completion (WFC), and word-stem
      completion (WSC). This result occurred regardless of the mode of study response
      (written or spoken) or whether the generation condition was compared with reading
      words in or out of context. Rhyme generation did not produce priming on the
      letter height task (Masson & MacLeod, 2002), implying that the effect was not
      mediated by covert visualization. Nor was the effect due to the mere presence of
      the rhyme cue. Semantic generation (from definitions) produced a different
      pattern, exhibiting a reverse generation effect on WFC and WSC but full (read
      level) priming on perceptual identification. The present results were not
      consistent with accounts based on the standard transfer-appropriate processing
      view, covert visualization, explicit contamination, or conceptual contributions
      to nominally perceptual tasks.

PMID- 19857022
TI  - Increased or reversed? The effect of surprise on hindsight bias depends on the
      hindsight component.
AB  - Two diverging hypotheses concerning the influence of surprising events on
      hindsight effects have been proposed: Although some authors believe that
      surprising events lead to a reversal of hindsight bias, others have proposed that
      surprise increases hindsight bias. Drawing on the separate-components view of the
      hindsight bias (which argues that hindsight bias consists of 3 independent
      components: memory distortions, impressions of inevitability and impressions of
      foreseeability), we reconcile these 2 perspectives by relating them to
      foreseeability and inevitability. Specifically, we assume that reversals in
      hindsight bias are to be found when foreseeability is considered, and increases
      in hindsight bias are found when inevitability is considered. To test these
      assumptions, we arranged for participants to learn about a highly surprising
      outcome and subsequently judge its foreseeability and inevitability. Results were
      consistent with our hypotheses: Participants perceived a highly surprising but
      explainable outcome to be both more inevitable and less foreseeable than
      participants who did not received outcome information. On the basis of
      experimentally induced dissociations between hindsight components, the present
      results thus strongly support the separate-components view of the hindsight bias.

PMID- 19857023
TI  - No evidence for temporal decay in working memory.
AB  - What drives forgetting in working memory? Recent evidence suggests that in a
      complex-span task in which an irrelevant processing task alternates with
      presentation of the memoranda, recall declines when the time taken to complete
      the processing task is extended while holding the time for rehearsal in between
      processing steps constant (Portrat, Barrouillet, & Camos, 2008). This time-based
      forgetting was interpreted in support for the role of time-based decay in working
      memory. In this article, we argue the contrary position by (a) showing in an
      experiment that the processing task in Portrat et al.'s (2008) study gave rise to
      uncontrolled post-error processes that occupied the attentional bottleneck, thus
      preventing restorative rehearsal, and (b) showing that when those post-error
      processes are statistically controlled, there is no evidence for temporal decay
      in Portrat et al.'s study. We conclude that currently there exists no direct
      evidence for temporal decay in the complex-span paradigm.

PMID- 19857024
TI  - Context-dependent semantic priming in number naming.
AB  - Previous research has shown that time to name single-digit Arabic numbers is
      about 15 ms slower when naming trials are interleaved with simple multiplication
      (e.g., state product of 2 x 3) than when naming digits is interleaved with
      magnitude comparison (e.g., state larger; 2 upward arrow 3). To explain this
      phenomenon, J. I. D. Campbell and A. W. S. Metcalfe (2008) proposed that the
      comparison context enables both semantic and asemantic pathways for digit naming
      but that number-fact retrieval inhibits the semantic route and slows digit naming
      relative to the comparison context. To test this hypothesis, the authors modified
      the naming context paradigm by introducing a semantic priming manipulation. They
      replicated the digit-naming response time advantage for comparison relative to
      the multiplication context and observed semantic priming only in the comparison
      context. In comparison blocks, digit naming was 8 ms faster immediately after
      naming near digit primes (+/-1) compared to far primes (>or=3), but in
      multiplication blocks there was no priming. The results reinforce the theory that
      number-fact retrieval can inhibit the semantic route for digit naming (L. Cohen &
      S. Dehaene, 1995) and thereby reconfigure the cognitive architecture for naming
      digits.

PMID- 19857025
TI  - The influence of memory on perception: it's not what things look like, it's what
      you call them.
AB  - World knowledge influences how we perceive the world. This study shows that this
      influence is at least partly mediated by declarative memory. Dutch and German
      participants categorized hues from a yellow-to-orange continuum on stimuli that
      were prototypically orange or yellow and that were also associated with these
      color labels. Both groups gave more "yellow" responses if an ambiguous hue
      occurred on a prototypically yellow stimulus. The language groups were also
      tested on a stimulus (traffic light) that is associated with the label orange in
      Dutch and with the label yellow in German, even though the objective color is the
      same for both populations. Dutch observers categorized this stimulus as orange
      more often than German observers, in line with the assumption that declarative
      knowledge mediates the influence of world knowledge on color categorization.

PMID- 19857026
TI  - Cue strength as a moderator of the testing effect: the benefits of elaborative
      retrieval.
AB  - The current study explored the elaborative retrieval hypothesis as an explanation
      for the testing effect: the tendency for a memory test to enhance retention more
      than restudying. In particular, the retrieval process during testing may activate
      elaborative information related to the target response, thereby increasing the
      chances that activation of any of this information will facilitate later
      retrieval of the target. In a test of this view, participants learned cue-target
      pairs, which were strongly associated (e.g., Toast: Bread) or weakly associated
      (e.g., Basket: Bread), through either a cued recall test (Toast: _____) or a
      restudy opportunity (Toast: Bread). A final test requiring free recall of the
      targets revealed that tested items were retained better than restudied items, and
      although strong cues facilitated recall of tested items initially, items recalled
      from weak cues were retained better over time, such that this advantage was
      eliminated or reversed at the time of the final test. Restudied items were
      retained at similar rates on the final test regardless of the strength of the cue
      target relationship. These results indicate that the activation of elaborative
      information-which would occur to a greater extent during testing than restudying-
      may be one mechanism that underlies the testing effect.

PMID- 19857027
TI  - Unspoken knowledge: implicit learning of structured human dance movement.
AB  - The sequencing of dance movements may be thought of as a grammar. We investigate
      implicit learning of regularities that govern sequences of unfamiliar, discrete
      dance movements. It was hypothesized that observers without prior experience with
      contemporary dance would be able to learn regularities that underpin structured
      human movement. Thirty-one adults were assigned to either an exposure or a
      control group. Exposure consisted of 22 grammatical 3-, 4-, and 5-movement
      sequences presented twice in random order; sequence duration ranged from 9 to 19
      s. In a test phase, exposure and control groups identified previously unseen
      sequences as grammatical or ungrammatical, and rated confidence of judgment. The
      exposure group selected significantly more new grammatical sequences in the test
      phase than the control group. In addition, for the exposure group, the zero
      correlation criterion, wherein no relation between confidence and accuracy
      indicates unconscious knowledge, was satisfied. Through exposure, novice
      observers can learn a grammar that governs the sequencing of dance movements.
      This has implications for implicit learning of long sequences, working memory,
      and the development of expectations through exposure to contemporary dance.

PMID- 19857028
TI  - Examining the relationships among item recognition, source recognition, and
      recall from an individual differences perspective.
AB  - The authors of the current study examined the relationships among item
      recognition, source-recognition, free recall, and other memory and cognitive
      ability tasks via an individual differences analysis. Two independent sources of
      variance contributed to item-recognition and source-recognition performance, and
      these two constructs related differentially to other memory and cognitive ability
      constructs. The results are in accordance with a dual-process theory of memory
      retrieval in which a familiarity process can support judgments of previous
      occurrence and a more strategic recollection process is needed for controlled
      search of long-term memory. Furthermore, the authors offer additional evidence in
      favor of a dual-process model by showing validity for these two unique sources of
      variance.

PMID- 19857029
TI  - Anticipated reward enhances offline learning during sleep.
AB  - Sleep is known to promote the consolidation of motor memories. In everyday life,
      typically more than 1 isolated motor skill is acquired at a time, and this
      possibly gives rise to interference during consolidation. Here, it is shown that
      reward expectancy determines the amount of sleep-dependent memory consolidation.
      Subjects were trained on 2 different sequences of a finger sequence motor task
      before 12-hr retention intervals of either nocturnal sleep or daytime
      wakefulness. After training was finished, reward expectancy was varied by
      announcing a monetary reward for performance improvement at retesting on either
      the first- or second-trained sequence. Before the retest, however, subjects were
      informed that reward would depend not on only 1 sequence but on the average
      performance for both sequences. Posttraining sleep enhanced overall finger
      sequence performance. The sleep-dependent gain in skill was significantly greater
      for the sequence that was associated with monetary reward after training,
      regardless of whether this sequence was the first or second to be trained. After
      wake retention intervals, no or only minor performance gains were observed. The
      data show that expectancy for a reward enhances offline learning of a skill
      during sleep.

PMID- 19857030
TI  - Eat less and exercise more - is it really enough to knock down the obesity
      pandemia?
AB  - Reduced physical activity and abundant energy intake are two most common factors
      leading to uncontrolled body weight gain. But these factors are not under entire
      internal consciousness control; they are also partially genetically determined
      and are affected by for example food marketing practices. In addition to these
      two widely accepted factors, there are some other factors, whose could also
      contribute to the recent increase of obesity prevalence. For example, non
      exercise activity thermogenesis, sleeping habits, more stable inside room
      temperatures (using of heating and air conditioning), high prescription of
      medications with weight gain as side effect, psychosocial factors, unfavourable
      socioeconomic status and unpleasant urban environment are the background factors
      which should not be omitted if obesity/BMI determination should be fully
      understood and kept under control. In conclusion, unhealthy life style is
      necessary, but not sufficient for obesity development.

PMID- 19857031
TI  - Antioxidants and vitamins in clinical conditions.
AB  - Various reactive oxygen species (ROS) may be produced from normal biochemical,
      essential metabolic processes or from external sources as exposure to a variety
      of agents presented in the environment. Lipids, proteins, carbohydrates and DNA
      are all capable of reacting with ROS and can be implicated in etiology of various
      human disorders (rheumatoid arthritis, reperfusion injury, atherosclerosis, lung
      diseases etc.). In the organism damage by ROS is counteracted with natural
      antioxidants (glutathione peroxidases, superoxide dismutases, catalase,
      glutathione, ubiquinol, uric acid, and essential minerals) and nutritional
      antioxidants from diet (i.e. vitamins E, C, carotenoids). Possible mechanisms of
      nutritional depletion and side effects of high intake are in the article
      described.

PMID- 19857032
TI  - Omega-3 fatty acids and cardiovascular disease risk: do we understand the
      relationship?
AB  - There is a large body of evidence documenting the effects of long-chain
      polyunsaturated fatty acids with the first double bond at the third position from
      methyl-terminal (so called omega-3 fatty acids (FAs)) on different components of
      cardiovascular disease (CVD) risk. However, it may seem the more answers on the
      topic we learn, the more questions remain to be elucidated. There are three
      levels of evidence documenting the impact of fish omega-3 FAs on CVD risk.
      Epidemiological data have shown unequivocally the increased intake of fish is
      associated with lower CVD morbidity and mortality. Numerous experimental studies
      have shown (almost always) positive effects of omega-3 FAs on lipoprotein
      metabolism, coagulation and platelet function, endothelial function, arterial
      stiffness etc. Most importantly, there are a few prospective clinical endpoint
      trials (DART, JELIS, GISSI Prevenzione and GISSI-HF) that have examined the
      impact of omega-3 FAs supplementation on cardiovascular outcomes in different
      patient populations. Recent meta-analyses of these and other clinical studies
      have yielded somewhat conflicting results. In this review we will summarize
      current evidence of omega-3 FAs effects on cardiovascular risk focusing on new
      data from recent clinical trials as well as possible practical implications for
      clinical practice.

PMID- 19857033
TI  - Association between duration of the sleep and body weight.
AB  - Some studies have suggested that there could be an association between the
      duration of sleep in humans and development of the obesity. We have analyzed the
      group of the probands (n = 3970, 2038 males and 1932 females, aged 18-65 years),
      with permanent address in the Central or South Bohemia. We ascertained the
      relationship between the duration of their sleep (obtained per questionnaire) and
      body mass index, weight, height, the value of systolic and diastolic blood
      pressure, heart rate, waist and hip circumference, the values of total-, high
      density- and low density- cholesterol, thyroid hormone and body exercise
      performed. The optimal values of the body mass index (and optimal body weight)
      were associated with the duration of sleep 7 hours per night (P < 0.001). This
      association was found both in males and females and in both districts. Other
      anthropometrical and biochemical parameters were not associated with the sleep
      duration.

PMID- 19857034
TI  - Life style change and reverse cholesterol transport in obese women.
AB  - HDL cholesterol resp. apolipoprotein A1 concentrations are tools to estimate
      individual CVD risk, although only a part of HDL particles participate in reverse
      cholesterol transport (RCT). This discrepancy was analyzed in life style change
      based on increase of physical activity and dietary counseling. Efflux of
      cholesterol from pre-labeled macrophages to plasma acceptors of tested
      individuals was used as an RCT measure. Changes of lipoprotein parameters,
      glucose, fasting insulin concentrations and RCT were analyzed in 15 obese women
      after 9-week intervention consisted of 5 sessions of increased physical activity
      per week. Controlled increase in physical activity for 9 weeks induced a decrease
      of body weight averaging 9 kg (ranged from 2.3 to 15.5 kg). The intervention
      leads to significant decreases of triglycerides, apoprotein A1 and apoprotein B
      concentration, whereas total cholesterol, LDL cholesterol and HDL cholesterol did
      not change significantly. The increase of RCT was not significant, but there was
      highly significant negative correlation between individual decrease of body
      weight and an increase of RCT. Significant increase of RCT was found in 13
      persons with a weight reduction more than 3.5 kg. Substantial weight loss is
      necessary to increase RCT.

PMID- 19857035
TI  - Importance of knowledge on lipid composition of foods to support development
      towards consumption of higher levels of n-3 fatty acids via freshwater fish.
AB  - The need of better labelling of fats in processed animal origin products is
      urgent. The lack of information makes it possible to exclude n-3 fatty acids in
      preparations of foods. The higher fat content, the higher n-6/n-3 ratio seems to
      be a rule. It is desirable to broaden the labelling into which oils have been
      used when foods are processed. The dietary balance of n-6 and n-3 fatty acids is
      important for homeostasis and normal development in humans. The ratio between n
      6/n-3 fatty acids suggested to be evolutionary developed is between 1 and 4. The
      main conclusion is that the fat sources used during processing and preparation of
      convenient foods have the largest impact on the food FA content and composition.
      A proposal is therefore that this should be declared on the product label
      especially the n-3 FA content. It is also of large importance to increase
      consumption of freshwater fish fed suitable feeds containing n-3 fatty acids in
      central Europe to enable a generally lower n-6/n-3 ratio in the human diet.
      Therefore optimizing feeds to freshwater fish in culture is urgent and important.

PMID- 19857036
TI  - Actigenetic of ACE gene polymorphism in Czech obese sedentary females.
AB  - Obesity is a serious health problem worldwide and many genes have been implicated
      in determination of obesity, but our knowledge of the genes responsible for
      individual differences in weight loss after physical intervention are poor. One
      of the candidate genes is a gene for angiotensin-converting enzyme (ACE) ant its
      insertion/deletion (I/D) polymorphism. We have analyzed the association between
      the ACE gene variant in intervened obese females. Twenty four unrelated healthy
      obese (BMI > 29.9 kg/m(2), with abdominal type of obesity) premenopausal (age
      between 25 and 45 years) Czech Caucasian sedentary and non-diabetic females, pre
      selected according the ACE I/D polymorphism (twelve II and twelve DD homozygotes)
      were studied in a medical research centre. They underwent 9 weeks intervention
      program (combination of the lowering of dietary intake to optimal level for the
      age and 3 times a week physical activity at fitness centre). The participants
      were supervised to sustain a heart rate of 65 % of maximum. Anthropometrical,
      biochemical parameters and body composition (Bodystat 1500) were analyzed before
      and after the intervention. Our study suggest, that in Czech Caucasian females
      I/D polymorphism within the ACE gene will have no major effect on weight loss.
      Interestingly, we have detected, that in obese females II genotype was associated
      with higher increase in basal metabolic rate (202 kcal per day) then in DD
      homozygotes (p<0.05), thus at least under some circumstances, this genetic
      variant may have an slight effect on BMI development.

PMID- 19857037
TI  - Volunteer's willingness to genetic testing - lack of the understanding of the
      matter.
AB  - Medical genetic research achieved in last decade many efforts leading to better
      understanding of inherited basis of human diseases. This will not be possible
      without the participation of patients and controls. However, the general
      understanding of the background and possibilities of genetic association studies
      is very low. It was confirmed by study of university of students. Because of the
      fair of misuses of the individual genetic information, significant part of
      participants refused the use of already donated blood samples for genetic testing
      but agreed with using of buccal swabs for the same analysis. To enhance the
      general knowledge's of the population, leading to realistic expectations not just
      about genetic predictive power but also about the eventual risks in behind will
      be the major mission in the next years.

PMID- 19857038
TI  - Nutrition as prevention and treatment of osteoporosis.
AB  - Osteoporosis is a systemic disease of the skeleton, characterized by reduction of
      bone mass and concurrent deterioration of bone structure. Consequently, bones are
      more fragile, and there is increased risk of fractures. The potential for
      acquisition of maximum bone mass is influenced by a number of factors. Among
      those are heredity, sex, nutrition, endocrine factors, mechanical influences and
      some risk factors. The best documented nutrient for metabolism of bone is
      calcium. Major role in the pathogenesis of osteoporosis have some micro and macro
      nutrients, prebiotics, alcohol, alternative diets, starvation and anorexia. Meta
      analysis of 29 randomized trials showed that supplementation with calcium and
      vitamin D3 reduces risk of bone fractures by 24 % and significantly reduces loss
      of bone mass. Osteoporosis has multi factor etiology. Osteoporosis is one of
      diseases which are influenced by nutrition and life style. It is preventable by
      means of adequate nutrition and sufficient physical activity.

PMID- 19857039
TI  - The role of neoadjuvant therapy in sphincter-saving surgery for mid and distal
      rectal cancer.
AB  - Current treatment of mid and lower rectal cancer includes neoadjuvant therapy,
      such as radiotherapy or radiochemotherapy. Randomized trials have demonstrated
      that neoadjuvant therapy improves local control. However, with the exception of
      one study, it does not improve overall and cancer-specific survival. In addition,
      the role of neoadjuvant therapy in enhancing the surgeon's ability to perform
      sphincter-saving surgery is still controversial. We provide an overview of
      reported randomized trials using neoadjuvant therapy in patients with rectal
      cancer. We have examined the most significant factors influencing sphincter
      preservation and the manner in which these factors are affected by neoadjuvant
      treatment.

PMID- 19857040
TI  - Prospective study on combination of electrical impedance scanning and ultrasound
      in estimating risk of development of breast cancer in young women.
AB  - Based on cost-effective ratio, there has not yet been imaging methods suitable
      for breast cancer screening in young women. The aim of this study was to evaluate
      the sensitivity and specificity of the combination of electrical impedance
      scanning (EIS) and ultrasound in identifying breast cancer for young women, to
      calculate relative risks, and to determine whether there has been some more
      accurate imaging method used in early detection of breast cancer in young women.
      A prospective and multicenter clinical study was conducted in young women aged 45
      years and under. The young women (583 cases) scheduled for mammary biopsy
      underwent EIS and ultrasound, respectively. EIS and ultrasound results were
      compared with final histopathology results. Study end points included
      sensitivities and specificities of EIS, ultrasound and the combination method, as
      well as relative probability of breast cancer of positive patients detected by
      the combination of EIS and ultrasound. Of the 583 cases, 143 were diagnosed with
      breast cancer. The sensitivities of EIS, ultrasound and the combination method
      were 86.7% (124/143), 72% (103/143), and 93.7% (134/143); the specificities were
      72.9% (321/440), 82.5% (363/440), and 64.1% (282/440), and the relative
      possibilities of breast cancer for the positive young women detected by EIS,
      ultrasound, and the combination method were 8.67, 5.77, and 14.84, respectively.
      The combination of EIS and ultrasound is likely to become an applicable method
      for early detection of breast cancer in young women.

PMID- 19857041
TI  - Aberrant changes of Wnt2/beta-catenin signaling pathway induced by sodium
      nitroprusside in human esophageal squamous cell carcinoma cell lines.
AB  - Inhibition of Wnt/beta-catenin pathway is an attractive method for therapy of
      various tumors including breast, colorectal, and cervical cancer, etc. However,
      little is known about the role of Wnt2/beta-catenin pathway in esophageal
      squamous cell carcinoma (ESCC). Here we identify that Wnt2/beta-catenin signaling
      pathway is activated in ESCC cells, and sodium nitroprusside (SNP) and siRNA
      against beta-catenin not only inhibit the expressions of beta-catenin and its
      major downstream effectors including c-myc and cyclin D1, but induce cell cycle
      arrest and apoptosis, suggesting that Wnt2/beta-catenin pathway may be a
      potential molecular target for ESCC therapy.

PMID- 19857042
TI  - Role of histone modifications and DNA methylation in the regulation of O6
      methylguanine-DNA methyltransferase gene expression in human stomach cancer
      cells.
AB  - To determine a possible function of histone modifications in stomach
      carcinogenesis, we analyzed global and MGMT-promoter levels of di-methyl-H3-K9,
      di-methyl-H3-K4 and acetyl-H3-K9, as well as MGMT DNA methylation and mRNA
      expression following treatment with 5-aza-2' -deoxycytidine and/or Trichostatin
      A. We found that histone H3-K9 di-methylation, H3-K4 di-methylation, H3-K9
      acetylation and DNA methylation work in combination to silence MGMT. The results
      indicate that histone modifications as well as DNA methylation may be involved in
      stomach carcinogenesis. In addition to its effect on DNA methylation, 5-aza-2' 
      deoxycytidine can act at histone modification level to reactivate MGMT expression
      in a region-specific and DNA methylation-dependent manner.

PMID- 19857043
TI  - UGT genomic diversity: beyond gene duplication.
AB  - The human uridine diphospho (UDP)-glucuronosyltransferase (UGT) superfamily
      comprises enzymes responsible for a major biotransformation phase II pathway: the
      glucuronidation process. The UGT enzymes are located in the endoplasmic reticulum
      of almost all tissues, where they catalyze the inactivation of several endogenous
      and exogenous molecules, including bilirubin, sex steroids, numerous prescribed
      drugs, and environmental toxins. This metabolic pathway is particularly variable.
      The influence of inheritable polymorphisms in human UGT-encoding genes has been
      extensively documented and was shown to be responsible for a fraction of the
      observed phenotypic variability. Other key genomic processes are likely
      underlying this diversity; these include copy-number variations, epigenetic
      factors, and newly discovered splicing mechanisms. This review will discuss novel
      molecular aspects that may be determinant to UGT phenotypes.

PMID- 19857044
TI  - Design, synthesis, and pharmacological evaluation of novel oxadiazole and
      oxadiazoline analogs as anti-inflammatory agents.
AB  - Two novel series of oxadiazole and oxadiazoline analogs possessing an indole
      nucleus were synthesized for their potential anti-inflammatory activity. The
      structures of the compounds were elucidated by elemental and spectral (IR, (1)H
      NMR, (13)C-NMR, and MS) analysis. Most of the test compounds demonstrated
      appreciable anti-inflammatory activities. The anti-inflammatory activity of
      oxadiazoles at doses of 100 mg/kg was shown by their ability to provide 27-66%,
      14-32%, and 20-51%. protection against carrageenan-induced rat paw edema, moist
      cotton pellet-induced, and dry cotton pellet-induced granuloma, respectively. On
      the other hand, the anti-inflammatory properties of oxadiazolines at doses of 100
      mg/kg were reflected by their ability to provide 20-56%, 11-26%, and 25-47%
      protection against carrageenan-induced rat paw edema, moist cotton pellet
      induced, and dry cotton pellet-induced granuloma, respectively. The ulcerogenic
      potential of the compounds was determined. Structure-activity relationships among
      synthesized compounds were also established.

PMID- 19857045
TI  - Use of fluorochrome labels in in vivo bone tissue engineering research.
AB  - The use of fluorochromes in bone research is a widely accepted technique that
      dates back to the 1950s. Several pioneers, such as Harold Frost, have thoroughly
      investigated the potential of fluorochrome use for the study on bone formation
      and bone remodeling dynamics. Since the development of bone tissue engineering, a
      renewed interest in the benefits of fluorochrome use was perceived. Fluorochrome
      use in animal models makes it possible to determine the onset time and location
      of osteogenesis, which are the fundamental parameters in bone tissue engineering
      studies. There is, however, a lack of standardized procedures for using this
      technique. In addition, many types of fluorochromes exist and one could be
      confused upon selecting the appropriate type, the appropriate concentration, the
      route of administration, and methods of visualization. All these variables can
      potentially affect the outcome during fluorescence microscopy. This work aims at
      providing the bone tissue engineering researcher with an overview of the history,
      working mechanism, and the potential pitfalls in the use of fluorochromes in
      animal studies. Experiments using some of the more frequently used fluorochromes
      are explained and illustrated.

PMID- 19857046
TI  - Independent association of sleep quality, fatigue, and vital exhaustion with
      platelet count in patients with a previous venous thromboembolic event.
AB  - Elevated platelet count might reflect increased inflammation as an etiological
      factor for venous thromboembolism (VTE). Poor sleep, fatigue, and exhaustion are
      all associated with inflammation and are also common sequelae of chronic
      psychological stress that previously predicted increased risk of VTE. We
      hypothesized that platelet count would be high in patients with VTE who sleep
      poorly and who are fatigued and exhausted. We investigated 205 patients scheduled
      for thrombophilia work-up > or =3 months after an objectively diagnosed venous
      thromboembolic event. They completed the Jenkins Sleep Questionnaire to rate
      subjective sleep quality and the short forms of the Multidimensional Fatigue
      Symptom Inventory and Maastricht Vital Exhaustion Questionnaire. Platelet count
      was determined by a mechanical Coulter counter. Analyses controlled for age, sex,
      body mass index, time since the index event, and medication. After taking into
      account these covariates, poorer sleep quality (p = 0.001; DeltaR(2)= 0.046),
      high fatigue (p = 0.008; DeltaR(2)= 0.032), and vital exhaustion (p = 0.050;
      DeltaR(2)= 0.017) were all associated with elevated platelet count. In addition,
      high level of fatigue mediated the relationship between poor sleep quality and
      elevated platelet count (p = 0.046). Poor sleep quality, high levels of fatigue,
      and vital exhaustion were identified as correlates of an elevated platelet count
      in patients with a previous episode of VTE. Given the emerging role of
      inflammatory processes in VTE, the findings suggest a mechanism through which
      behavioral and chronic psychological stressors might contribute to incident and
      recurrent venous thrombotic events.

PMID- 19857047
TI  - Time does not heal every wound: coronary stent thrombosis of a bare-metal stent
      more than one decade after its implantation.
AB  - In the present report, we describe a unique case of very late stent thrombosis
      with a bare-metal stent that occurred more than a decade after stent
      implantation. Potential explanations for the late stent thrombosis are non
      compliance to aspirin, late acquired malapposition of the stent, progression of
      atherosclerosis or in-stent restenosis. In our patient, none of these
      explanations seems to have played a role. Although the occurrence of (very) late
      stent thrombosis is not uncommon with drug-eluting stent (DES), it is rather
      unusual with bare-metal stent (BMS). Nevertheless, cardiologists should be aware
      of the potential complication of late stent thrombosis, even with bare-metal
      stents.

PMID- 19857048
TI  - Treatment of faun-tail naevus with intense pulsed light.
AB  - BACKGROUND: Faun tail is a rare cutaneous marker of spinal dysraphism. This
      neurological abnormality may lead to difficulties such as severe pain and burning
      sensations in treatment of hypertrichosis of faun tail with laser or laser-like
      devices. OBJECTIVE: We evaluated outcomes of an intense pulsed light source in
      two patients with faun tail. METHODS: The Lumina intense pulsed light system [650
      nm handpiece (550-1100 nm)] was used for the treatment. Magnetic resonance
      imaging and neurological examination were done. RESULTS: Tethered cord syndrome
      was detected as a neurological abnormality. The patients were treated with an
      energy fluence of 18- 26 J/cm(2), pulse sequencing of 3 to 4, and a delay time of
      20-35 ms. Local anesthesia was applied in one patient during treatment for severe
      pain sensation. A mean of 85% hair reduction was achieved. CONCLUSION: A good
      cosmetic result with intense pulsed light treatment was achieved in the patients
      with faun tail. Local anesthesia may be required before treatment of faun tail
      with laser or laser-like systems due to associated neurological abnormalities.

PMID- 19857049
TI  - Mechanochemical synthesis and in vitro anti-Helicobacter pylori and uresase
      inhibitory activities of novel zinc(II)-famotidine complex.
AB  - The mechanochemical synthesis and characterization of a zinc complex with
      famotidine is described. The complex was characterized by microanalysis and a
      number of spectroscopic techniques. The complex was of M:L dihydrate type.
      Derivatization of famotidine with zinc appears to enhance the activity of the
      drug by inhibiting the growth of Helicobacter pylori (two reference and 34
      clinical isolates). The complex inhibited the growth of H. pylori in an MIC range
      of 1-8 microg mL(-1). The anti-H. pylori activity of the zinc-famotidine complex
      against antibiotic-resistant strains was nearly comparable to that of antibiotic
      susceptible strains. The complex was found to be far less toxic than the parent
      drug, as demonstrated by its higher LD(50) value. In the human urease enzyme
      inhibition assay the complex exhibited significant inhibition. The new complex
      appears to be more useful in eradicating both the antibiotic-susceptible and
      antibiotic-resistant strains of H. pylori.

PMID- 19857050
TI  - Healing of surgical wounds made with lambda970-nm diode laser associated or not
      with laser phototherapy (lambda655 nm) or polarized light (lambda400-2000 nm).
AB  - OBJECTIVE: The aim of this study was to analyze the effect of two phototherapies,
      laser and polarized light, on diode laser (970lambda nm) wounds. BACKGROUND DATA:
      Lasers have been used in surgery, and some wavelengths may cause thermal damage
      to the tissue and affect healing. Several studies have shown that some
      wavelengths are effective in improving healing. Coherent and noncoherent light
      have been successfully used on the modulation of biological phenomena of several
      origins. ANIMALS AND METHODS: Thirty-one Wistar rats were divided into 3 groups
      (GI to GIII). A 20-mm x 2-mm wound was created on the dorsum of each animal with
      a diode laser (Sirolaser, Sirona, Bensheim, Germany). Group GI acted as control.
      On GII, laser light (lambda655 nm, 30 mW, phi approximately 3 mm, 12 J/cm(2)) was
      used and on GIII illumination with polarized light (lambda400-2000 nm, 40 mW, phi
      approximately 5.5 cm, 12 J/cm(2)) was used, every other day (GII) or daily (GIII)
      for 7 days. The animals were killed at 0, 7, and 14 days after surgery. Specimens
      were taken, routinely processed, stained and imunnomarked [HE (hematoxylin
      eosin), sirius red, alpha-smooth muscle actin (SMA)], and underwent histological
      analysis. RESULTS: GII showed better response at day 14 when re-epithelialization
      was in a more advanced stage. The number of myofibroblasts was significantly
      different over the healing time (7 to 14 days); this number was smaller than that
      observed on G1. On GIII at day 7, the number of myofibroblasts was significantly
      higher than for GII. At day 14, a more pronounced deposition of collagen matrix
      was also seen, and inflammation was discrete and more advanced for GIII.
      CONCLUSION: The results of the present study showed that the effect of the use of
      laser light was more evident at early stages of healing and that the use of
      polarized light improved the resolution of the inflammatory reaction, increased
      the deposition of collagen, increased the number of myofibroblasts, and quickened
      re-epithelialization during the experimental time.

PMID- 19857051
TI  - Effect of GaAlAs laser irradiation on enzyme activity.
AB  - OBJECTIVE: The aim of this study was to determine the influence of laser
      irradiation on enzyme activity. BACKGROUND DATA: Enzymes are catalysts of
      extraordinary efficiency, able to accelerate reactions by manifold. Enzyme laser
      light activation is currently a fast-growing field and a large number of studies
      have been produced. MATERIALS AND METHODS: Liquid CNPG amylase and control serum
      (Qualitrol 1H) were used in the experiments. Laboratory analysis of alpha-amylase
      was performed on two sample groups: (i) E + S and (ii) E + S + L, in six
      repetitions per irradiation dose. Group 2 was irradiated with gallium-aluminum
      arsenide (GaAlAs) 904 nm at doses of 0.01, 0.1, 0.5, and 1 J/cm(2). Enzyme
      activity was read using a spectrophotometer equipped with a thermostatic chamber
      capable of precise absorbance measurement at 405 nm. RESULTS: The results were
      analyzed with the Student's t-test, and the percentage of enzyme activity was
      determined. Photomodulation of alpha-amylase activity by GaAlAs laser was
      analyzed following irradiation with different doses. Irradiation doses from 0.01
      to 1 J/cm(2) led to differences in enzyme activity: 0.01 J/cm(2) (0.10%), 0.1
      J/cm(2) (13.44%), 0.5 J/cm(2) (12.57%), and 1 J/cm(2) (-6.10%). CONCLUSION:
      Irradiation doses of 0.1 J/cm(2) and 0.5 J/cm(2) led to statistically significant
      increases in enzyme activity in comparison to the control. The similar curves of
      the effects of temperature and pH on enzymatic activity observed in this study
      suggest that laser irradiation also possess an optimum dose to modulate the
      enzymatic activity. That is, enzymes have an optimum laser dose (or range) at
      which their activity is maximal, whereas at higher or lower doses activity
      decreases.

PMID- 19857052
TI  - Membrane fluidity and the surface properties of the lipid bilayer: ESR experiment
      and computer simulation.
AB  - Penetration of the liposome membranes formed in the gel phase from DPPC (DPPC
      liposomes) and in the liquid-crystalline phase from egg yolk lecithin (EYL
      liposomes) by the TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and 16 DOXYL (2
      ethyl-2-(15-methoxy-oxopentadecyl)-4,4-dimethyl-3-oxazolidinyloxy) spin probes
      has been investigated. The penetration process was followed by 120 hours at
      24(0)C, using the electron spin resonance (ESR) method. The investigation of the
      kinetics of the TEMPO probe building into the membranes of both types of
      liposomes revealed differences appearing 30 minutes after the start of the
      experiment. The number of TEMPO particles built into the EYL liposome membranes
      began to clearly rise, aiming asymptotically to a constant value after about 100
      minutes, whereas the number of the TEMPO particles built into the DPPC liposome
      membranes was almost constant in time. The interpretation of the obtained
      experimental results was enriched with those of computer simulation, following
      the behavior of the polar heads (dipoles) of the lipid particles forming a lipid
      layer due to the change in the value of the model parameter, k, determining the
      mobility of the dipoles. The possibility of the formation of an irregular
      ordering of the polar part of lipid membranes was proved, which leads to the
      appearance of spaces filled with of water for k > 0.4. The appearance of these
      defects enables the penetration of the bilayer by the TEMPO particles. The
      limited mobility of lipid polar heads (k < 0.2) prevents the appearance of such
      areas facilitating the penetration of the lipid membrane by alien particles in
      the gel phase.

PMID- 19857053
TI  - Evolution of the human diet: linking our ancestral diet to modern functional
      foods as a means of chronic disease prevention.
AB  - The evolution of the human diet over the past 10,000 years from a Paleolithic
      diet to our current modern pattern of intake has resulted in profound changes in
      feeding behavior. Shifts have occurred from diets high in fruits, vegetables,
      lean meats, and seafood to processed foods high in sodium and hydrogenated fats
      and low in fiber. These dietary changes have adversely affected dietary
      parameters known to be related to health, resulting in an increase in obesity and
      chronic disease, including cardiovascular disease (CVD), diabetes, and cancer.
      Some intervention trials using Paleolithic dietary patterns have shown promising
      results with favorable changes in CVD and diabetes risk factors. However, such
      benefits may be offset by disadvantages of the Paleolithic diet, which is low in
      vitamin D and calcium and high in fish potentially containing environmental
      toxins. More advantageous would be promotion of foods and food ingredients from
      our ancestral era that have been shown to possess health benefits in the form of
      functional foods. Many studies have investigated the health benefits of various
      functional food ingredients, including omega-3 fatty acids, polyphenols, fiber,
      and plant sterols. These bioactive compounds may help to prevent and reduce
      incidence of chronic diseases, which in turn could lead to health cost savings
      ranging from $2 to $3 billion per year as estimated by case studies using omega-3
      and plant sterols as examples. Thus, public health benefits should result from
      promotion of the positive components of Paleolithic diets as functional foods.

PMID- 19857054
TI  - Regular tart cherry intake alters abdominal adiposity, adipose gene
      transcription, and inflammation in obesity-prone rats fed a high fat diet.
AB  - Obesity, systemic inflammation, and hyperlipidemia are among the components of
      metabolic syndrome, a spectrum of phenotypes that can precede the development of
      type 2 diabetes and cardiovascular disease. Animal studies show that intake of
      anthocyanin-rich extracts can affect these phenotypes. Anthocyanins can alter the
      activity of tissue peroxisome proliferator-activated receptors (PPARs), which
      affect energy substrate metabolism and inflammation. However, it is unknown if
      physiologically relevant, anthocyanin-containing whole foods confer similar
      effects to concentrated, anthocyanin extracts. The effect of anthocyanin-rich
      tart cherries was tested in the Zucker fatty rat model of obesity and metabolic
      syndrome. For 90 days, rats were pair-fed a higher fat diet supplemented with
      either 1% (wt/wt) freeze-dried, whole tart cherry powder or with a calorie- and
      macronutrient-matched control diet. Tart cherry intake was associated with
      reduced hyperlipidemia, percentage fat mass, abdominal fat (retroperitoneal)
      weight, retroperitoneal interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha) expression, and plasma IL-6 and TNF-alpha. Tart cherry diet also increased
      retroperitoneal fat PPAR-alpha and PPAR-gamma mRNA (P = .12), decreased IL-6 and
      TNF-alpha mRNA, and decreased nuclear factor kappaB activity. In conclusion, in
      at-risk obese rats fed a high fat diet, physiologically relevant tart cherry
      consumption reduced several phenotypes of metabolic syndrome and reduced both
      systemic and local inflammation. Tart cherries may reduce the degree or
      trajectory of metabolic syndrome, thereby reducing risk for the development of
      type 2 diabetes and heart disease.

PMID- 19857055
TI  - The grape component piceatannol induces apoptosis in DU145 human prostate cancer
      cells via the activation of extrinsic and intrinsic pathways.
AB  - Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol that is found
      in grapes, red wine, Rheum undulatum, and the seeds of Euphorbia lagascae. It has
      been previously reported that piceatannol inhibits the proliferation of a variety
      of cancer cell types. In the present study, we assessed the effects of
      piceatannol on the growth of androgen-insensitive DU145 prostate cancer cells at
      concentrations of 1-10 micromol/L. Piceatannol reduced the viable numbers and
      increased the numbers of apoptotic DU145 cells in a dose-dependent manner.
      Western blot analysis revealed that piceatannol increased the protein levels of
      cleaved caspase-8, -9, -7, and -3 and cleaved poly(ADP-ribose) polymerase (PARP).
      Piceatannol increased mitochondrial membrane permeability and cytochrome c
      release from the mitochondria to the cytosol. Piceatannol induced an increase in
      the levels of truncated Bid, Bax, Bik, Bok, and Fas but caused a decrease in the
      levels of Mcl-1 and Bcl-xL. Caspase-8 and -9 inhibitors mitigated piceatannol
      induced apoptosis. The caspase-8 inhibitor suppressed the piceatannol-induced
      cleavage of Bid, caspase-3, and PARP. These results indicate that piceatannol
      induces apoptosis via the activation of the death receptor and mitochondrial
      dependent pathways in prostate cancer cells.

PMID- 19857056
TI  - trans-10,cis-12 Conjugated linoleic acid induces depolarization of mitochondrial
      membranes in HT-29 human colon cancer cells: a possible mechanism for induction
      of apoptosis.
AB  - Conjugated linoleic acid (CLA), which is naturally present in a variety of foods
      such as milk fat and the meat of ruminant animals, has been demonstrated to exert
      chemoprotective effects in several tissues in experimental animals. CLA is a
      collective term, which denotes one or more positional and geometric isomers of
      octadecadienoic acid, with cis-9,trans-11 (c9t11) and trans-10,cis-12 CLA
      (t10c12) being the principal isomers in commercial preparations. We observed
      previously that physiological levels of CLA inhibited HT-29 cell growth, and the
      growth inhibitory effects of CLA were attributed to the effect of t10c12, but not
      c9t11. In the present study, we assessed the mechanisms by which physiological
      levels of CLA and t10c12 induce apoptosis in HT-29 cells. HT-29 cells were
      cultured for 3 days in serum-free medium in the presence of various
      concentrations of CLA (0-20 micromol/L) or t10c12 (0-4 micromol/L). Addition of
      CLA or t10c12 to culture medium resulted in a dose-dependent increase in the
      numbers of apoptotic cells. The results of western blot analysis of total cell
      lysates showed that CLA and t10c12 increased the levels of cleaved caspase-9,
      caspase-3, and poly(ADP-ribose) polymerase but did not alter the levels of Bcl-2
      family member proteins. However, these fatty acids were shown to increase the
      translocation of Bad and Bax to the mitochondria, increase mitochondrial membrane
      permeability, and induce the release of cytochrome c and Smac/Diablo from the
      mitochondria. In addition, CLA and t10c12 diminished Akt content and Akt
      phosphorylation. These findings indicate that physiological levels of t10c12
      induce apoptosis in HT-29 colon cancer cells, which is mediated via mitochondrion
      mediated events associated with a decline in Akt activity, an increase in the
      translocation of the pro-apototic Bad and Bax to the mitochondria, and the
      subsequent disruption of normal mitochondrial membrane potential.

PMID- 19857057
TI  - Octanoate and decanoate induce apoptosis in 3T3-L1 adipocytes.
AB  - The effect of octanoate and decanoate, respectively, eight- and 10-carbon medium
      chain fatty acids (MCFAs), on apoptotic signaling in 3T3-L1 adipocytes was
      investigated. 3T3-L1 adipocytes were treated with various concentrations of
      octanoate or decanoate. Cell viability, apoptosis, and expression of apoptosis
      related proteins were investigated. Results indicated that both octanoate and
      decanoate decreased viability, increased apoptosis, and increased reactive oxygen
      species production. Immunoblotting analysis showed an increase in the levels of
      cytoplasmic cytochrome c and cleaved poly(ADP-ribose) polymerase by octanoate and
      decanoate. Concomitantly, we observed that pro-caspase-3 was decreased, resulting
      in the induced accumulation of the cleaved form of caspase-3 by both octanoate
      and decanoate. In addition, both octanoate and decanoate increased the expression
      of pro-apoptotic Bax with an accompanied decrease of anti-apoptotic Bcl-2. These
      results show that octanoate and decanoate mediate adipocyte apoptosis via a
      caspase-dependent mitochondrial pathway in 3T3-L1 adipocytes. MCFAs thus decrease
      adipocyte number by initiating the apoptotic process in 3T3-L1 adipocytes.

PMID- 19857058
TI  - Anti-invasive activity of anthocyanins isolated from Vitis coignetiae in human
      hepatocarcinoma cells.
AB  - We investigated anti-invasive effects of the anthocyanins from fruits of Vitis
      coignetiae Pulliat (known as meoru in Korea) on human hepatoma Hep3B cells. The
      anthocyanins inhibited cell invasion in a dose-dependent manner as measured by
      Matrigel (BD Biosciences, San Jose, CA, USA) invasion assays. They also inhibited
      expression of matrix metalloproteinase (MMP)-2 and MMP-9 and activation of
      nuclear factor kappaB (NF-kappaB) stimulated by tumor necrosis factor alpha.
      Taken together, the results of this study indicate that the anthocyanins isolated
      from fruits of V. coignetiae Pulliat have anti-invasive effects on human hepatoma
      Hep3B cells and inhibit MMP-2 and MMP-9 gene expression at least in part through
      the inhibition of NF-kappaB activation.

PMID- 19857059
TI  - Protection against hypercholesterolemia by Corni fructus extract and its related
      protective mechanism.
AB  - To reduce cardiovascular disease (CVD) by reducing circulating cholesterol
      concentrations, much attention has been focused on the search for dietary
      interventions for hypercholesterolemia. Corni Fructus is known to exhibit several
      biological activities. Therefore, in the present study, its protective effect on
      diet-induced hypercholesterolemia was studied using a rat model fed 1%
      cholesterol and 0.5% cholic acid. Corni Fructus extract was administered at an
      oral dose of 50, 100, or 200 mg/kg of body weight/day for 10 days. The
      administration inhibited the elevation of both systolic and diastolic blood
      pressure. In addition, it lowered serum total cholesterol levels with a decrease
      in esterified cholesterol. Moreover, the atherogenic index was decreased in a
      dose-dependent manner, suggesting its protective role against CVD through
      regulating cholesterol and lipoprotein levels. The hepatic levels of total and
      free cholesterol were also reduced by Corni Fructus. This implies that free
      cholesterol was used for catabolism or efflux. Consequently, the levels of total
      cholesterol and bile acid in feces were significantly increased. Our present
      results also showed that the administration of Corni Fructus decreased lipid
      peroxidation, suggesting a protective effect against oxidative stress induced by
      hypercholesterolemia. Furthermore, hypercholesterolemic control rats had
      significantly lower expression of sterol regulatory element-binding protein
      (SREBP)-2 protein without any difference in SREBP-1 protein expression. On the
      other hand, the protein expression of SREBP-2 was significantly up-regulated by
      Corni Fructus. Furthermore, the protein expression of peroxisome proliferator
      activated receptor alpha was elevated, indicating that Corni Fructus would
      activate fatty acid oxidation. In conclusion, Corni Fructus may protect against
      CVD by regulating blood pressure, cholesterol levels, and expression of proteins
      related to lipid metabolism.

PMID- 19857060
TI  - Flow cytometric analysis of age-related changes in intestine intraepithelial
      lymphocyte subsets and their functional preservation after feeding mice on
      spirulina.
AB  - We investigated age-related changes in intestinal intraepithelial lymphocyte
      (IEL) subsets in mice by flow cytometric analysis and their functional
      preservation as affected by feeding Spirulina, a cyanobacterium that is known to
      possess various therapeutic effects, including immune modulation activity. The
      number of cells possessing the leukocyte-common antigen CD45(+) cells in mice (43
      weeks old) of the aged group, used as a representative marker for IELs, was
      significantly lower than that of adult mice (5 weeks old). Either the proportion
      or the number of CD45(+)CD8(+) cells of the aged mice was significantly lower
      than that of adult mice, corresponding to previous reports. Proportions and
      numbers of CD4(+)CD8(+) cells in aged mice, on the other hand, were higher than
      those in adult mice. Increased or decreased levels of the cell surface antigens
      observed in the aged mice tended to be restored in aged mice fed Spirulina (aged
      SP group), which ingested a hot water extract of Spirulina (SpHW). In fact, the
      proportions of CD45(+)CD8(+) cells and CD45(+)TCRgammadelta(+) cells in the aged
      SP group significantly increased in comparison to the control aged group, which
      ingested ordinary chow and water ad libitum. These results suggest that ingestion
      of SpHW in the aged-SP group may contribute to the functional preservation of the
      intestinal epithelium as a first line of mucosal barrier against infectious
      agents through retaining the number of certain IELs. Changes in the number of
      other IEL subsets and blood cells are also discussed.

PMID- 19857061
TI  - Neuroprotective effects of onion extract and quercetin against ischemic neuronal
      damage in the gerbil hippocampus.
AB  - Onion has several well-known biological functionalities, including antioxidant
      effects, and contains quercetin (3,3',4,5,7-pentahydroxyflavone), a powerful
      antioxidant. In the present study, we observed neuroprotective effects of onion
      extract (OE) and its major component, quercetin, on ischemic damage in the gerbil
      hippocampus, which is related to memory function. Repeated treatment with 100
      mg/kg OE and 20 mg/kg quercetin for 15 days before ischemic surgery protected
      pyramidal neurons of the hippocampal CA1 region from ischemic damage. In the OE
      treated ischemic group, gliosis (activation of astrocytes and microglia) was
      attenuated in the CA1 4 days after ischemia/reperfusion. In addition, treatment
      with OE and quercetin decreased protein levels of 4-hydroxy-2-nonenal (a marker
      for lipid peroxidation) in the ischemic CA1. We suggest that repeated
      administration of OE and quercetin can protect against neuronal damage from
      transient cerebral ischemia.

PMID- 19857062
TI  - Actions of ferulic acid and vitamin E on prevention of hypercholesterolemia and
      atherogenic lesion formation in apolipoprotein E-deficient mice.
AB  - This study was carried out to investigate whether dietary vitamin E and ferulic
      acid (FA) can exert possible interactions on preventions of hypercholesterolemia
      and atherogenic lesion formation in C57BL/65 apolipoprotein E-deficient (apo E(-/
      )) mice. Four-week-old male apo E(-/-) mice were randomly divided into three
      groups and given one of three types of Western diets with various amounts of
      vitamin E (0.02%, 0%, or 0.2%) for 15 weeks. FA was added to vitamin E-free
      Western diet and vitamin E-rich Western diet at the 0.02% level. The plasma total
      cholesterol concentration was significantly lowered when FA was added to the
      vitamin E-free and vitamin E-rich Western diet as compared to the normal vitamin
      E Western diet (0.02% vitamin E), and this was accompanied with a decreased
      hepatic acyl-coenzyme A:cholesterol acyltransferase activity. The hepatic and
      erythrocyte thiobarbituric acid-reactive substances levels were significantly
      lowered when FA was added to the vitamin E-rich Western diet, which was
      attributable to increased activities of antioxidant enzymes (superoxide
      dismutase, catalase, and glutathione peroxidase) and paraoxonase. Accordingly,
      vitamin E and/or FA are beneficial for prevention of hypercholesterolemia and
      atherogenesis in apo E(-/-) mice. In particular, dietary FA exhibited an anti
      atherosclerotic property, and this effect was synergistically enhanced with the
      vitamin E supplement.

PMID- 19857063
TI  - Effects of orally administered Actinidia arguta (Hardy Kiwi) fruit extract on 2
      chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in
      NC/Nga mice.
AB  - Atopic dermatitis (AD) is characterized by highly pruritic, chronic, relapsing
      inflammatory skin lesions. Furthermore, therapeutic choices are limited,
      especially in long-standing cases, despite its increasing prevalence. This study
      was performed to examine the clinical efficacy and the therapeutic mechanism
      underlying the effects of Actinidia arguta (hardy kiwi) fruit extract in an
      animal model of AD. To examine the effects of A. arguta extract on AD, 2-chloro
      1,3,5-trinitrobenzene-treated NC/Nga mice were orally administered A. arguta
      extract (100 mg/kg/day), tacrolimus (1 mg/kg/day), or dexamethasone (3 mg/kg/day)
      for 8 weeks. Skin severity scores, epidermal thickening, mast cell infiltration
      and degranulation, total serum immunoglobulin (Ig) isotypes (IgE, IgG(1)), and
      cytokine (interleukin [IL]-4 and interferon [IFN]-gamma) and Toll-like receptor
      (TLR) (TLR-2, TLR-4, and TLR-9) expressions were examined in each of the study
      groups. Orally administered A. arguta extract significantly reduced clinical
      dermatitis severity, epidermal thickness, mast cell dermal infiltration and
      degranulation, and total levels of serum IgE and IgG(1). Furthermore, this
      suppression of total serum IgE and IgG(1) levels was accompanied by a decrease in
      IL-4 and an increase in IFN-gamma expression in skin and splenocytes.
      Interestingly, TLR-9 expression was increased by oral A. arguta extract. This
      study confirms that A. arguta extract has potential as a dietary therapeutic
      agent for the treatment of AD. Furthermore, our findings suggest that its
      clinical efficacy and mode of action against AD are associated with the
      modulation of biphasic T-helper (Th) 1/Th2 cytokines, with the inhibition of Th2
      mediated IgE overproduction, and possibly with the up-regulation of TLR-9.

PMID- 19857064
TI  - Anti-inflammatory and analgesic activities of Chaenomeles speciosa fractions in
      laboratory animals.
AB  - The prescription of current existing anti-inflammatory drugs is hampered by their
      adverse effects over time. Botanical extracts are thought to be a potential
      source of a natural anti-inflammatory property with fewer adverse effects.
      Chaenomeles speciosa has long been used as an herbal medicine for treatment of
      various diseases such as rheumatoid arthritis, prosopalgia, and hepatitis. Until
      now there have been no reports on the specific anti-inflammatory fractions of
      extract of C. speciosa (ECS). In the present study the anti-inflammatory
      activities of different fractions of ECS were evaluated using carrageenan-induced
      paw edema in rats. The 10% ethanol fraction (C3) was found to have stronger anti
      inflammatory effects compared with other fractions at the same dose. We also
      found that chlorogenic acid was one of the active constituents responsible for
      the anti-inflammatory effect using bioassay-guided fractionation by means of high
      performance liquid chromatography. Compared with controls, fraction C3
      demonstrated significant anti-inflammatory activity in the xylene-induced ear
      edema test (P < .01), acetic acid-induced peritoneal capillary permeability test,
      and the cotton pellet granuloma test in mice or rats (P < .01); it also showed
      marked analgesic activity in the acetic acid-induced abdominal contraction test
      and formalin-induced paw licking test in mice and rats (P < .05 or .01). However,
      fraction C3 showed no significant effect in the hot plate test in mice. These
      findings justify the use of the C. speciosa for treating pain and inflammation.
      These results support the proposal of C. speciosa fraction C3 as a potential anti
      inflammatory agent.

PMID- 19857066
TI  - Effect of Chlorella vulgaris on glucose metabolism in Wistar rats fed high fat
      diet.
AB  - The aim of this study was to examine the effect of Chlorella vulgaris on glucose
      metabolism in rats fed a high fat diet. Sixty 6-week-old male Wistar rats were
      divided into two groups: normal diet group (N group) and high fat diet group (H
      group); then the rats in each group were further divided into three subgroups and
      fed either Chlorella-free diets or diets with 5% (C5) or 10% (C10) (wt/wt)
      Chlorella for 9 weeks. Serum leptin concentration was significantly lower in the
      NC10 and HC10 groups than in the N and H groups. The fasting glucose
      concentration and homeostasis model assessment of insulin resistance of the HC10
      group were significantly lower than those of the H group. Glutamate transporter 4
      protein expression was significantly higher in the HC10 group than the H group.
      In conclusion, 10% Chlorella intake was more effective for blood glucose
      regulation than 5% Chlorella intake in rats fed a high fat diet. Chlorella intake
      may prevent insulin resistance in Wistar rats fed a high fat diet.

PMID- 19857065
TI  - Inulin increases glucose transport in C2C12 myotubes and HepG2 cells via
      activation of AMP-activated protein kinase and phosphatidylinositol 3-kinase
      pathways.
AB  - Inulin, a naturally occurring, functional food ingredient found in various edible
      plants, has been reported to exert potential health benefits, including decreased
      risk of colonic diseases, non-insulin-dependent diabetes, obesity, osteoporosis,
      and cancer. However, the mechanism of the antidiabetic activity of inulin has not
      yet been elucidated. In this study, we showed that inulin increased the uptake of
      glucose in C2C12 myotubes, which was associated with both AMP-activated protein
      kinase (AMPK) and phosphatidylinositol 3-kinase (PI3-K) signaling pathways, but
      both of these pathways appeared to transmit their signals in an independent
      manner. Moreover, we found that inulin was able to increase the uptake of glucose
      in C2C12 myotubes in which insulin resistance was induced by exposing cells to
      high glucose concentrations. The identical effects of inulin were also observed
      in HepG2 hepatoma cells. Collectively, we report the antidiabetic activity of
      inulin and further demonstrate for the first time that such activity is
      associated with AMPK and PI3-K activation.

PMID- 19857067
TI  - Isoalantolactone from Inula helenium caused Nrf2-mediated induction of
      detoxifying enzymes.
AB  - Our previous study demonstrated that methanolic extract of Inula helenium
      (Elecampane) has the potential to induce detoxifying enzymes such as
      NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) activity and
      glutathione S-transferase (GST) and found isoalantolactone and alantolactone as
      the active components. In this study we investigated the detoxifying enzyme
      inducing potential of isoalantolactone, which is present in I. helenium and has a
      structure similar to that of alantolactone. The compound induced QR in a dose
      dependent manner in both Hepa1c1c7 cells and its mutant BPRc1 cells lacking the
      arylhydrocarbon receptor translocator. Like with most phase 2 enzyme inducers,
      other phase 2 detoxifying enzymes, including GST, glutathione reductase, gamma
      glutamylcysteine synthetase, and heme oxygenase-1, were also induced by
      isoalantolactone in a dose-dependent manner in the cultured cells. Furthermore,
      isoalantolactone caused a proportionate increase in luciferase activity depending
      upon concentration and exposure time in the reporter assay in which HepG2-C8
      cells, transfectants carrying antioxidant response element-luciferase gene, were
      used. The nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) was
      stimulated by the compound and attenuated by phosphatidylinositol 3-kinase
      inhibitors such as LY294002 and wortmannin. In conclusion, isoalantolactone is a
      candidate for chemoprevention and acts as potent phase 2 enzyme inducer by
      stimulating the accumulation of Nrf2 in the nucleus.

PMID- 19857068
TI  - Fenugreek bread: a treatment for diabetes mellitus.
AB  - Use of fenugreek, a food with demonstrated efficacy in lowering blood sugar, is
      limited by its bitter taste and strong flavor. A bread incorporating fenugreek
      using a proprietary process was tested for its taste acceptability and its effect
      on carbohydrate metabolism. We developed a fenugreek bread formula that was
      produced in a commercial bakery by incorporating fenugreek flour into a standard
      wheat bread formula. Whole wheat bread was prepared by the same formula in the
      same bakery using wheat flour. Eight diet-controlled diabetic subjects were
      served two slices (56 g) and 5% fenugreek. Blood glucose and insulin were tested
      periodically over a 4-hour period after consumption. The tests were run on two
      occasions 1 week apart, once with the fenugreek bread and once with regular
      bread. The study was double-blind, and the order was randomized and balanced.
      Fenugreek and whole wheat bread samples were evaluated for sensory attributes and
      nutrient composition. There was no statistically significant difference in
      proximate composition, color, firmness, texture, and flavor intensity between the
      fenugreek and wheat bread (P > .05). The area under the curve for glucose and
      insulin was lower in the fenugreek condition, but only reached significance with
      insulin (P < .05). The fenugreek-containing bread was indistinguishable from the
      whole wheat bread control. Normally, fenugreek flour impacts bread quality
      negatively. The bread maintained fenugreek's functional property of reducing
      insulin resistance. Acceptable baked products can be prepared with added
      fenugreek, which will reduce insulin resistance and treat type 2 diabetes.

PMID- 19857069
TI  - Antimicrobial activity of two propolis samples against human Campylobacter
      jejuni.
AB  - The aim of this study was to analyze the antimicrobial activity of two ethanolic
      extracts of propolis (EEPs) and selected flavonoids against 16 Campylobacter
      jejuni clinical isolates and several Gram-positive and Gram-negative human
      pathogens. The antimicrobial activity of EEPs and flavonoids was evaluated by the
      agar well diffusion method. The EEPs inhibited the growth of C. jejuni,
      Enterobacter faecalis, and Staphylococcus aureus. The most active flavonoid was
      galangin, with the highest percentage of sensitivity among C. jejuni strains
      (68.8%); lower percentages of sensitivity were observed for quercetin (50%). The
      minimal inhibitory concentrations (MICs) of EEPs and flavonoids for C. jejuni
      isolates were determined by the agar dilution method. EEPs showed MIC values of
      0.3125-0.156 mg/mL for all C. jejuni strains; galangin and quercetin gave MICs
      ranging from 0.250 to 0.125 mg/mL. Thus propolis preparations could be used as
      support to traditional therapy for Campylobacter infection, especially when the
      antibiotic agents show no activity against this microorganism.

PMID- 19857070
TI  - Bioactive compounds and antioxidant and antiproliferative activities of Korean
      white lotus cultivars.
AB  - In traditional Korean medicine, lotus (Nelumbo nucifera Gaertn) roots have been
      used as an antidiabetic and an antiproliferative remedy. However, scientific
      publications on lotus properties are very limited. Therefore, it was decided to
      investigate the Korean white lotus cultivars in order to find out their
      bioactivity. It was found that all lotus cultivars (Inchisa, Muan, Garam, and
      Chungyang) possess high amounts of bioactive compounds: total phenols, between
      7.95 +/- 0.8 and 4.21 +/- 0.3 mg of gallic acid equivalents (GAE)/g dry weight
      (DW); ascorbic acid, between 15.8 +/- 1.1 and 22.3 +/- 1.7 mg of ascorbic acid/g
      DW; and amino acids, between 15.05 +/- 0.82% and 16.62 +/- 0.90% DW. The highest
      contents of polyphenols (7.95 +/- 0.8 mg of GAE/g DW) and the highest levels of
      antioxidant [by 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and 1,1
      diphenyl-2-picrylhydrazyl assays, 54.27 +/- 6.1 and 21.98 +/- 2.5 microM Trolox
      equivalents/g DW, respectively] and antiproliferative activities on both human
      cancer cell lines (Calu-6 for human pulmonary carcinoma and SMU-601 for human
      gastric carcinoma, 59.75 +/- 3.99% and 71.21 +/- 2.79% cell viability,
      respectively) were found in the Chungyang cultivar. Fluorometry and Fourier
      transform infrared spectroscopy can be applied as rapid methods for determination
      of bioactive compounds, such as polyphenols. The correlation between the
      bioactive compounds and the antioxidant activity was high. In conclusion, all
      Korean white lotus cultivars are valuable medicinal foods, and in order to
      receive the best results a combination of lotus cultivars has to be consumed.

PMID- 19857071
TI  - In vitro bile acid binding and short-chain fatty acid profile of flax fiber and
      ethanol co-products.
AB  - Fibers from flaxseed and co-products from ethanol production could be potential
      sources of dietary fiber in human diet. In vitro fermentation and bile acid
      binding models were used to investigate the metabolic effects of lignaMax
      (Bioriginal Food and Science Corp., Saskatoon, SK, Canada) flax meal, spent flax
      meal, soluble flax gum, wheat insoluble fiber (WIF), and rye insoluble fiber
      (RIF). Wheat and rye bran were used as reference samples. Bile acid binding of
      substrates was analysed at taurocholate ([(14)C]taurocholate) concentration of
      12.5 mM. Soluble flax gum showed the highest bile acid binding (0.57 micromol/mg
      of fiber) (P <or= .05). There was no difference in bile acid binding between
      wheat bran (0.2 micromol/mg of fiber) and WIF (0.26 micromol/mg of fiber). RIF
      had higher (P <or= .05) bile acid binding (0.20 micromol/mg of fiber) than rye
      bran (0.13 micromol/mg of fiber). Substrates were hydrolyzed and incubated with
      pig fecal samples. Short-chain fatty acid (SCFA) profile and gas accumulation
      (G(f)) were compared. Soluble flax gum generated the highest amount of acetic and
      propionic acids. SCFA profiles of wheat/rye brans and WIF/RIF were similar
      (except for butyric acid). G(f) for soluble flax gum was greater (P < .001) than
      that of spent flax meal. G(f) values of the wheat samples were similar, whereas
      the G(f) of the rye bran was higher (P < .001) than that of RIF. Fractional
      degradation rate (micro(t = T/2)) (P < .001) was also recorded. The highest mu(t
      = T/2) was observed for the soluble flax gum. Oil-depleted flaxseed fractions and
      WIF/RIF (co-products from ethanol production) could be potential sources of
      dietary fiber in human nutrition.

PMID- 19857073
TI  - Frozen fruit pulp of Euterpe oleraceae Mart. (Acai) prevents hydrogen peroxide
      induced damage in the cerebral cortex, cerebellum, and hippocampus of rats.
AB  - Oxidative stress is implicated in several human illnesses, including neurological
      disorders such as Parkinson's and Alzheimer's diseases. Acai is largely consumed
      in Brazil and contains high levels of antioxidant compounds. This work aims to
      study the antioxidant activity of acai frozen fruit pulp in the cerebral cortex,
      hippocampus, and cerebellum of rats treated with the oxidizing agent hydrogen
      peroxide (H(2)O(2)). Pretreatment of tissue with acai decreased H(2)O(2)-induced
      damage of both lipids and proteins in all tissues tested. This fruit was also
      able to reduce the activities of the antioxidant enzymes superoxide dismutase and
      catalase to basal levels. We observed a negative correlation between the
      polyphenol content of acai and the levels of lipid (r = -0.689; P <or= .05) and
      protein damage (r = -0.569; P <or= .05), suggesting the participation of
      polyphenols in the observed antioxidant activity. These data suggest that acai
      has a positive contribution in the development of age-related neurodegenerative
      diseases.

PMID- 19857072
TI  - The aporphine alkaloid boldine induces adiponectin expression and regulation in
      3T3-L1 cells.
AB  - Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical
      studies suggest a negative correlation between oxidative stress and adiponectin
      levels in patients with metabolic syndrome or cardiovascular disease. Natural
      compounds that can prevent oxidative stress mediated inhibition of adiponectin
      may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the
      medicinal plant Peumus boldus, is a powerful antioxidant. The current study
      demonstrates the effects of boldine on the expression of adiponectin and its
      regulators, CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome
      proliferator-activated receptor (PPAR)-gamma, in 3T3-L1 cells. Differentiated 3T3
      L1 adipocytes were exposed to either hydrogen peroxide (H(2)O(2)) (100 microM) or
      tumor necrosis factor-alpha (TNFalpha) (1 ng/mL) for 24 hours in the presence or
      absence of increasing concentrations of boldine (5-100 microM). Quantitative
      polymerase chain reaction showed that both the oxidants decreased the mRNA levels
      of adiponectin, PPARgamma, and C/EBPalpha to half of the control levels. Boldine,
      at all concentrations, counteracted the inhibitory effect of H(2)O(2) or TNFalpha
      and increased the expression of adiponectin and its regulators. The effect of
      boldine on adiponectin expression was biphasic, with the lower concentrations (5
      25 microM) having a larger inductive effect compared to higher concentrations (50
      100 microM). Boldine treatment alone in the absence of H(2)O(2) or TNFalpha was
      also able to induce adiponectin at the inductive phase of adipogenesis.
      Peroxisome proliferator response element-luciferase promoter transactivity
      analysis showed that boldine interacts with the PPAR response element and could
      potentially modulate PPAR responsive genes. Our results indicate that boldine is
      able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells
      and has the potential to be beneficial in obesity-related cardiovascular disease.

PMID- 19857074
TI  - Orthosiphon stamineus leaf extract protects against ethanol-induced gastropathy
      in rats.
AB  - Orthosiphon stamineus Benth., which is used as a gastroprotective herbal remedy
      in Malaysia, was assessed for its anti-ulcerogenic activity against ethanol
      induced ulcers in rats. Fifty percent methanol was used to extract the oven-dried
      O. stamineus leaves. The extract was then lyophilized with a rotary evaporator
      and freeze-dried. Oral administration of O. stamineus methanolic extract (OSME)
      (125, 250, 500, and 1,000 mg/kg) was found to significantly decrease the ulcer
      index (P < .01, P < .001, P < .001, and P < .001, respectively). Histological
      study of a section of the rat stomach also showed a marked improvement in the
      gastric mucosal damage in groups receiving OSME. In order to further investigate
      the gastroprotective mechanism of OSME, mucus secretion and lipid peroxidation
      level were estimated in vitro and ex vivo. OSME exhibited dose-dependent
      stimulation of mucus secretion (r = 0.718, P < .001) and inhibition of lipid
      peroxidation in rat gastric mucosal homogenates (both in vitro [r = 0.819, P <
      .05] and ex vivo [r = 0.981, P < .05]). It was concluded that the
      gastroprotective mechanism of OSME was partly due to its ability to inhibit lipid
      peroxidation and stimulate gastric mucus secretion.

PMID- 19857075
TI  - Effects of glucan on immunosuppressive actions of mercury.
AB  - Global cycling of mercury results in the presence of mercury salts in the
      environment. The well-established negative effects of mercury on the immune
      system led us to the study whether natural immunomodulator glucan can overcome
      the immunosuppressive effects of mercury. Two types of mercury, thimerosal and
      mercury acetate, were administered in a dose of 2-8 mg/L of drinking water to
      mice. After 2 weeks, all mice exhibited profound suppression of both cellular
      (phagocytosis, natural killer cell activity, mitogen-induced proliferation, and
      expression of CD markers) and humoral (antibody formation and secretion of
      interleukin-6, interleukin-12, and interferon-gamma) responses. The mice were
      then fed with a diet containing a standard dose of glucan. Our results showed
      that simultaneous treatment with mercury and glucan resulted in significantly
      lower immunotoxic effects of mercury, which suggests that glucans can be
      successfully used as a natural remedy of low-level exposure to mercury.

PMID- 19857076
TI  - Evaluation of the antioxidant effect of a new functional food enriched with
      Sideritis euboea in healthy subjects.
AB  - Sideritis euboea is a Greek plant that is traditionally consumed as a beverage
      (mountain tea). From in vitro studies, its extract has shown antioxidant and
      estrogenic activities. In our study we used S. euboea as an enriching food factor
      in order to produce a new functional food, a jelly dessert, in order to explore
      its antioxidant effects if consumed on a daily basis by healthy subjects. In this
      placebo-controlled clinical trial, 63 subjects were recruited for a 1-month
      nutritional intervention. Twelve subjects were excluded. The remaining 51
      subjects were randomly classified in the intervention group (daily consumption of
      the jelly containing 0.3 g of S. euboea extract) or the placebo group (daily
      consumption of the same jelly without the enrichment). Vitamins C, A, and E,
      glutathione, coenzyme Q10, total nitrites, nitrates, total nitrogen oxide,
      nitrites/nitrates ratio, and total antioxidant status were measured in blood
      samples before and after the intervention. After the intervention, free
      glutathione and coenzyme Q10 increased, and nitrites decreased significantly in
      both groups. The other antioxidant markers were not altered. No statistical
      significant differences were observed between the two groups. The daily
      consumption of the functional food, for 30 days, had no effects on the
      antioxidant status of healthy volunteers.

PMID- 19857077
TI  - Antioxidant and antigenotoxic activities of purple grape juice--organic and
      conventional--in adult rats.
AB  - Oxidative damage to biomolecules occurs by the accumulation of molecular damage
      due to free radicals and/or a diminution of antioxidant protection. The aim of
      this study was to evaluate the protection of organic and conventional purple
      grape juices in brain, liver, and plasma from adult Wistar rats (7 months old)
      against the oxidative damage provoked by carbon tetrachloride (CCl(4)). Adult
      rats were divided into three groups (control, conventional purple grape juice,
      and organic purple grape juice). Half of the rats received CCl(4), and the other
      half received the vehicle (vegetable oil). The chemical analytical determination
      showed that the highest levels of total phenolic, resveratrol, and catechins were
      seen in organic purple grape juices. Considering the treatment groups, it was
      observed that in all tissues (brain structures and liver) and plasma, CCl(4)
      treatment increased the lipid peroxidation (LP) levels. Both grape juices were
      capable to reduce LP levels in cerebral cortex and hippocampus; however, in the
      striatum and substantia nigra only the organic grape juice reduced LP level.
      CCl(4) caused an increase in catalase activity in cerebral cortex, hippocampus,
      and substantia nigra and in superoxide dismutase activity in substantia nigra.
      This increase was reduced by both juices in substantia nigra and hippocampus
      structures (P < .05). In the alkaline version of the comet assay performed on
      whole blood, it was observed that CCl(4) was capable of inducing mainly DNA
      damage class 4 and 3 frequencies, which was significantly reduced in groups that
      received both purple grape juices. This implies that both grape juices have an
      important antigenotoxic activity.

PMID- 19857078
TI  - Antioxidant potential of peels and fleshes of peaches from different cultivars.
AB  - Increasing recent interest in nutraceuticals and functional foods has led
      researchers to investigate the antioxidant potential of several fruits. This
      article evaluates the antioxidant potential and reactivity based on luminol
      enhanced chemiluminescence capacity of peach extracts (peels and fleshes) and the
      contribution of a major compound present in these extracts to antioxidant
      potential and reactivity. The results obtained showed that the extracts of peels
      and fleshes of Maciel, Leonense, and Eldorado peach cultivars present free
      radical scavenging activity in all concentrations tested, with a concentration
      dependent action. The immediate inhibition of chemiluminescence and the duration
      of this inhibition were significantly higher with the extracts than with the
      major compound (chlorogenic acid) alone, and it can be due to a synergistic or
      additive effect of other antioxidants present in the extracts. The 50% inhibitory
      concentration (IC(50)) values for peach extract and chlorogenic acid were 1.19
      microg/mL and 8.43 microg/mL, respectively, when total radical-trapping
      antioxidant potential was evaluated, whereas IC(50) values of 0.41 microg/mL and
      1.89 microg/mL was found when total antioxidant reactivity was evaluated in peach
      extract and chlorogenic acid, respectively. Chlorogenic acid presented a good
      contribution to antioxidant reactivity and potential, but the fruit extracts
      provide better antioxidant action. Peach could be of great interest as an
      important antioxidant source including chlorogenic acid, and it may provide
      health-promoting advantages to consumers by intake of this fruit or by
      utilization of its peels as antioxidant sources in industry.

PMID- 19857079
TI  - Physicochemical properties of the oil from the fruit of Blighia sapida and
      toxicological evaluation of the oil-based diet in Wistar rats.
AB  - The physicochemical properties of the oil from the fruit of Blighia sapida and
      the toxicological effect of the oil-based diet on some biochemical parameters of
      selected rat tissues and serum were studied. The smoke, flash, and fire points as
      well as peroxide, iodine, and acid values of the fruit oil were significantly
      lower (P < .05), whereas the specific gravity, relative density, saponification,
      and ester values compared well with soybean oil. The fruit oil yield was 20.02%.
      The oil consisted of 22.22% saturated, 56.43% monounsaturated, and 21.35%
      polyunsaturated fatty acids. It is richer than soybean oil in behenic,
      palmitoleic, oleic, gadoleic, erucic, and 9,12-eicosanoic acids by 15.70%, 0.89%,
      7.22%, 12.05%, 8.27%, and 21.35%, respectively. The liver- and kidney-body weight
      ratios as well as the serum concentrations of cholesterol and high-density
      lipoprotein cholesterol of the rats maintained on diet formulated with the oil
      from the fruit of B. sapida increased significantly (P < .05), but the
      triglyceride and atherogenic index decreased (P < .05). The low-density
      lipoprotein cholesterol concentration and the heart-body weight ratio of the rats
      fed with the fruit oil diet compared well (P > .05) with those on soybean oil
      based diet. Animals fed with the fruit oil-based diet had their activities of
      liver glutamate oxaloacetate transaminase and glutamate pyruvate transaminase as
      well as alkaline phosphatase activities of the liver and kidney decreased with
      corresponding increase in the serum enzymes. These results suggest that oil from
      B. sapida fruit could be edible and may be explored as raw materials in the
      paint, margarine, and soap industries. The oil is also unlikely to predispose the
      animals to cardiovascular risk, but may labilize the plasma membrane of the
      hepatocytes and nephrons. It may also have a negative effect on the metabolism
      and regulation of amino acid in the animals. Therefore, the oil from B. sapida
      fruit may not be completely safe for consumption.

PMID- 19857080
TI  - Protective effect of royal jelly and green tea extracts effect against cisplatin
      induced nephrotoxicity in mice: a comparative study.
AB  - The aim of the present study was to investigate the protective role of royal
      jelly (RJ) and green tea (GT) extracts on cisplatin (cDDP)-induced nephrotoxicity
      in adult albino mice. Albino mice were randomly divided into six groups: Group I
      (control) received a single intraperitoneal injection of isotonic saline (0.02
      mL/g), Group II received a single intraperitoneal injection of cDDP (7 mg/kg of
      body weight), Group III received RJ (100 mg/kg of body weight), Group IV received
      GT (100 mg/kg of body weight), Group V received RJ (100 mg/kg of body weight) +
      cDDP (7 mg/kg of body weight), and Group VI received GT (100 mg/kg of body
      weight) + cDDP (7 mg/kg of body weight). The concentrations of blood urea
      nitrogen (BUN) and creatinine were evaluated. In addition, kidney samples were
      taken for determination of tissue malondialdehyde (MDA) and reduced glutathione
      (GSH) levels. In addition, histopathological changes in kidneys were
      investigated. The results indicated that no significant differences in MDA, GSH,
      BUN, and creatinine levels were observed among the control group and groups
      treated with RJ alone and GT alone (P > .05). However, there was a significant
      increase in BUN and creatinine parameters after cDDP application in Groups II, V,
      and VI. The mice treated with only cDDP exhibited an increase in serum BUN and
      creatinine levels when compared to Groups V and VI (P < .05). Moreover, cDDP
      induced oxidative damage caused a significant decrease in GSH levels and a
      significant increase in MDA levels in kidneys (P < .05). RJ and GT
      supplementation attenuated cDDP-induced nephrotoxicity, which was manifested by
      stopping the elevation in serum creatinine and BUN levels. Moreover, RJ and GT
      supplementation restored GSH content and MDA production levels in the kidney
      tissue following cDDP treatment (P < .05). These products were also effective in
      protecting against cDDP-induced tissue damage in mouse kidneys. In conclusion,
      100 mg/kg of body weight doses of RJ and GT provided protection against cDDP
      induced nephrotoxicity, and both products can act as protector agents against
      cDDP-induced kidney damages.

PMID- 19857082
TI  - Assessment of nutritional quality of wild and cultivated Pleurotus sajor-caju.
AB  - The edible mushroom Pleurotus sajor-caju, cultivated on corncobs and obtained
      from the wild, was assessed by nutritional indices. The protein efficiency ratios
      obtained for the rats fed stalk diet (2.16) and that of rats fed native P. sajor
      caju cap diet (2.14) were not significantly different (P >or= .05) from one
      another but were lower than the casein control (2.50), whereas the value for the
      wild cap diet-fed rats (2.99) was significantly higher (P <or= .05) than the
      control. Net protein retention value obtained for rats fed cap diets was
      significantly higher (P <or= .05) than the control, whereas the value for the
      stalk-fed rats was not significantly different (P >or= .05) from the control.
      Biochemical parameters analyzed include serum albumin, total protein, and
      hemoglobin. Serum albumin concentrations of both the cultivated and wild cap diet
      fed rats were not significantly different (P >or= .05) from that of the control,
      whereas those of the two stalk diet-fed groups were significantly higher (P <or=
      .05) than the control. Hemoglobin concentrations were significantly higher (P
      <or= .05) in rats fed wild cap diet than in all other treatment groups. Serum
      total protein values of rats fed cultivated stalk and wild cap diets were
      significantly higher (P <or= .05) in rats fed wild cap diet than in all other
      treatment groups. Total protein values of rats fed cultivated stalk and wild cap
      diets were significantly higher than those of other groups. The preceding
      highlights the importance of cultivated and native P. sajor-caju as sources of
      high-quality protein that could contribute to nutritional adequacy in human
      diets.

PMID- 19857081
TI  - The safety of flavocoxid, a medical food, in the dietary management of knee
      osteoarthritis.
AB  - This study was designed to determine the safety of a medical food, flavocoxid, a
      proprietary blend of free-B ring flavonoids and flavans from the root of
      Scutellaria baicalensis (Chinese skullcap) and the bark of Acacia catechu in the
      dietary management of knee osteoarthritis. The 12-week, randomized, double-blind,
      placebo-controlled trial in an academic medical center enrolled 59 patients with
      moderate osteoarthritis of at least one knee who were recruited who were
      classified as having "below average" to "a moderately above average
      cardiovascular risk" with a Framingham-based scoring tool. Subjects were
      randomized to flavocoxid 250 mg twice a day versus identical placebo. Safety
      measures, including recording of adverse events, incidence of serious adverse
      events, and results of routine laboratory values, were compared between the two
      groups. There were no major differences in the baseline demographic
      characteristics of the placebo and flavocoxid groups. With one exception no
      significant differences were found between the two groups with respect to adverse
      events by body system, blood pressure, or laboratory values. There was a
      significantly higher incidence of upper respiratory adverse events in the placebo
      group (35.4% vs. 5.8%, P = .0003). There were no intra- or inter-group
      differences in any of the laboratory parameters from study baseline to
      completion. Thus, flavocoxid is safe when used in a population with "below
      average" to "moderately above average cardiovascular risk" compared to placebo.

PMID- 19857083
TI  - A comparative study of the antioxidant properties of two different species of
      Ocimum of southern Africa on alcohol-induced oxidative stress.
AB  - The present study investigates the protective effect of methanol extract of
      Ocimum gratissimum (MOEG) and Ocimum canum (MOEC) from Southern Africa on the
      oxidative stress induced by alcohol consumption. Male Wistar rats weighing 200
      250 g were divided into six groups of six rats each as follows: the normal
      control group was administered distilled water, the ethanol control was
      administered ethanol (5 g/kg), and experimental groups EX1 and EX3 were fed
      ethanol (5 g/kg) plus MOEG and MEOC (100 mg/kg), respectively. Two other
      experimental groups, EX2 and EX4, were administered MEOG and MEOC (100 mg/kg),
      respectively, for 30 days. At the end of the experiment, rats were sacrificed,
      and blood was collected to assay thiobarbituric acid-reactive substances (TBARS),
      reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and vitamins E and C.
      Results indicated a significant reduction in the levels of TBARS, ALT, and AST
      and a significant increase in the levels of GSH and vitamins E and C. The level
      of vitamin E is greater with MOEG treatment, whereas the vitamin C level goes up
      with MOEC treatment. A marked improvement occurred in the activities of CAT and
      SOD in groups EX1 and EX3 compared to the levels with group EC. Thus the results
      indicated a significant protection by these extracts against ethanol-induced
      hepatotoxicity (P <or= .05). Again the groups that were treated with extracts
      only (EX2 and EX4) showed low levels of TBARS, ALT, and AST, which clearly
      indicates the extract had no toxic effects on hepatocytes. Comparison of results
      for these two Ocimum species showed no significant difference except in the
      levels of vitamins E and C with two treatments. Thus there is a possibility that
      O. canum might be participating through vitamin C and O. gratissimum through
      vitamin E.

PMID- 19857084
TI  - Immunomodulatory effects of a standardized Lycium barbarum fruit juice in Chinese
      older healthy human subjects.
AB  - Lycium barbarum has been traditionally used in combination with several herbs for
      medicinal properties, but systematic modern clinical evaluation as a single herb
      has not been reported. To examine the systematic effects of L. barbarum on immune
      function, general well-being, and safety, we tested the effects of a standardized
      L. barbarum fruit juice (GoChi, FreeLife International, Phoenix, AZ, USA) at 120
      mL/day, equivalent to at least 150 g of fresh fruit, the amount traditionally
      used, or placebo for 30 days in a randomized, double-blind, placebo-controlled
      clinical study in 60 older healthy adults (55-72 years old). The GoChi group
      showed a statistically significant increase in the number of lymphocytes and
      levels of interleukin-2 and immunoglobulin G compared to pre-intervention and the
      placebo group, whereas the number of CD4, CD8, and natural killer cells or levels
      of interleukin-4 and immunoglobulin A were not significantly altered. The placebo
      group showed no significant changes in any immune measures. Whereas the GoChi
      group showed a significant increase in general feelings of well-being, such as
      fatigue and sleep, and showed a tendency for increased short-term memory and
      focus between pre- and post-intervention, the placebo group showed no significant
      positive changes in these measures. No adverse reactions, abnormal symptoms, or
      changes in body weight, blood pressure, pulse, visual acuity, urine, stool, or
      blood biochemistry were seen in either group. In conclusion, daily consumption of
      GoChi significantly increased several immunological responses and subjective
      feelings of general well-being without any adverse reactions.

PMID- 19857085
TI  - Antioxidant effects of garlic in young and aged rat brain in vitro.
AB  - Oxidative stress plays a key role in the pathogenesis of age-related
      neurodegeneration, and the nonenzymatic production of 8-iso-prostaglandin
      F(2alpha) (8-iso-PGF(2alpha)) may represent a reliable index of cellular
      oxidative damage. Garlic (Allium sativum) has been associated with peripheral
      antioxidant activities and therefore might prevent or reverse 8-iso-PGF(2alpha)
      production, but scant data are available on its possible neuroprotective effects.
      Therefore, we have studied the possible antioxidant effects of a garlic extract
      in rat brain synaptosomes obtained from young (3-month-old) and aged (14-month
      old) male Wistar rats that were perfused, in vitro, with graded concentrations of
      a garlic extract (10-500 microg/mL). Release in the effluent was evaluated, both
      in the basal state and after hydrogen peroxide-induced oxidative stress. In young
      rats, we observed a concentration-dependent inhibitory effect of the garlic
      extract on brain 8-iso-PGF(2alpha) production, both basally and after hydrogen
      peroxide-induced oxidative stimulus. In aged rats, 8-iso-PGF(2alpha) production
      was not affected by the garlic extract in the basal state, whereas, after
      hydrogen peroxide-induced oxidative stimulus, an antioxidant effect of the garlic
      extract appeared only at the higher concentration tested. In conclusion, garlic
      supplementation could be effective in preventing brain oxidative damage in young
      animals, whereas the aging brain seems to be resistant to the antioxidant effects
      of garlic, in vitro.

PMID- 19857086
TI  - Royal jelly reduces the serum glucose levels in healthy subjects.
AB  - Earlier biological investigations have shown that royal jelly has insulin-like
      activity. However, there have so far been no clinical trials to support these
      findings. The objective of the present study was to study the effect of royal
      jelly ingestion on the glucose metabolism of healthy humans. Twenty volunteers
      underwent the standardized oral glucose tolerance test (OGTT) and afterwards a
      second OGTT after ingestion of 20 g of royal jelly. Serum glucose levels after 2
      hours and the area under the curve for glucose were significantly lower (P =
      .041) after royal jelly administration. Substances originating from the
      pharyngeal glands of the honey bee with insulin-like activity are likely to have
      caused this effect and may thus be, at least partially, responsible for the
      lowering impact of honey on blood glucose levels. The identification of the
      substances that seem to act even after passage through the human stomach could
      lead to the development of new concepts in diabetology.

PMID- 19857087
TI  - Determination of acute toxicity of the aqueous extract of Potentilla erecta
      (Tormentil) rhizomes in rats and mice.
AB  - Potentilla erecta, the tormentil, and its rhizome extracts have been known for a
      long time in traditional medicine as a remedy for the treatment of inflammations,
      wounds, and gastrointestinal disorders. Tormentil rhizomes have also been used as
      part of alcoholic beverages in Germany, the Ukraine, and Russia. Acute toxicity
      of an aqueous P. erecta rhizome extract was evaluated with a single dose
      administered by the intragastric route to rats and mice in dosages of 2.5 g/kg
      and 6.8 g/kg of body weight, respectively. Further, a single dose of this extract
      was applied intraperitoneally to rats and mice in dosages of 3.8 and 14.5 g/kg of
      body weight, respectively. After an observation period of 2 weeks after
      intragastric administration and 3 days following intraperitoneal administration,
      no mortality or any changes in appearance, behavior, or body weight occurred for
      both rats and mice in the high dosages mentioned. Macroscopic and microscopic
      studies of the internal organs of these rodents revealed no pathological changes.
      The data are in line with the long-time traditional use of P. erecta rhizome
      extracts and results from recent clinical trials in which no signs of any toxic
      effects have been known after the administration of a P. erecta rhizome extract
      for the treatment of ulcerative colitis in adults and rotavirus-induced diarrhea
      in children. Thus P. erecta rhizome extracts should be considered safe with
      respect to acute toxicity when applied to humans.

PMID- 19857090
TI  - Sixth Annual Interdisciplinary Women's Health Research Symposium November 17,
      2009.

PMID- 19857095
TI  - Current and emerging pharmacologic therapies for the management of postmenopausal
      osteoporosis.
AB  - Postmenopausal osteoporosis is an asymptomatic skeletal disease that is often
      underdiagnosed and undertreated. Osteoporotic fractures are associated with
      substantial morbidity and mortality and impaired quality of life-socially,
      emotionally, and financially. Considering the growing burden of osteoporotic
      fractures worldwide, there remains an ongoing need for progress in the diagnosis
      of osteoporosis, identification of individuals at high fracture risk, and
      treatment to prevent fractures. Adequate intake of calcium and vitamin D is
      recommended as baseline therapy for osteoporosis prevention and treatment.
      Available pharmacological agents for the management of postmenopausal
      osteoporosis may not be appropriate for all women. Oral bisphosphonates are
      generally considered first-line therapy for patients with osteoporosis, but their
      use may be limited by gastrointestinal side effects. Other agents include hormone
      therapy, the selective estrogen receptor modulator (SERM) raloxifene, salmon
      calcitonin, teriparatide (human recombinant parathyroid hormone), and strontium
      ranelate (in some countries). Factors that may contribute to poor compliance and
      persistence with current osteoporosis therapies include drug intolerance,
      complexity of dosing regimens, and poor understanding of the relative benefit and
      risk with treatment. Emerging therapies for postmenopausal osteoporosis include
      novel SERMs (bazedoxifene, lasofoxifene, ospemifene, arzoxifene) and denosumab.
      Because SERMs can display mixed functional estrogen receptor agonist or
      antagonist activity depending on the target tissue, they may confer beneficial
      effects on bone with limited stimulation of other tissues (e.g., breast,
      endometrium). Clinical investigation of these promising new agents is ongoing to
      evaluate efficacy and safety, with the goal of developing effective strategies to
      maximize long-term tolerance, compliance, and persistence with therapy.

PMID- 19857096
TI  - Cost-effectiveness of hormone therapy in the United States.
AB  - OBJECTIVE: To estimate the cost-effectiveness of 5 years of treatment with
      hormone therapy (HT) compared with no treatment for women with menopausal
      symptoms in the United States. METHODS: A Markov cohort simulation model was used
      with tunnel techniques to assess the cost-effectiveness of HT in women aged 50
      years, based on a societal perspective. Clinical data, where possible, used
      results taken from the Women Health Initiative (WHI). The model had a lifetime
      horizon with cycle lengths of 1 year and contained the following disease states:
      hip fracture, vertebral fracture, wrist fracture, breast cancer, colorectal
      cancer, coronary heart disease, stroke, and venous thromboembolic events. An
      intervention was modelled by its impact on the disease risks during and after
      stopping treatment. The model required data on clinical effects, risks, mortality
      rates, quality of life weights, and costs. The main outcome of the model was cost
      per quality-adjusted life-year (QALY) gained on HT compared with no treatment.
      RESULTS: The results indicated that it was cost-effective to treat women with
      menopausal symptoms with HT in the United States. The severity of menopausal
      symptoms was the single most important determinant of cost-effectiveness, but HT
      remained cost-effective even where symptoms were mild or effects on symptom
      relief were small. CONCLUSIONS: Treatment of women with menopausal symptoms with
      HT is cost-effective.

PMID- 19857097
TI  - Gender bias in chronic lyme disease.

PMID- 19857099
TI  - Interaction of intravitreal combination drugs and the effect on the targeted
      site.
AB  - BACKGROUND: After evaluating experimentally the diffusion processes in the retina
      using peroxidase as a tracer material (previously published work), we found that
      junctional complexes of the retinal pigment epithelium and retinal capillaries
      were the major impediment to free diffusion between the retina and choroidal
      retinal blood vessels. These experiments indicated that to achieve high
      therapeutic concentrations of medications inside the eye, it was necessary to
      administer them by intravitreal injection. Soon after initial experimental work
      the necessity of combining antibiotics or antibiotics with steroids became
      obvious. As the use of intravitreal injection grew over the last 2 decades, so
      did the concept of combination therapy. METHODS: This review describes potential
      causes of drug-drug interaction and the rationale for combination therapy when
      injected into the vitreous cavity, encompassing publications between 1971 and
      2008. RESULTS: We describe the conditions that can cause physical-chemical
      interactions between the medications and the need for combination therapy for
      treatment of various intraocular disease processes. CONCLUSIONS: The intravitreal
      injection of medication and their combinations has become a part of standard care
      for many diseases of the retina and choroid. This article reviews the potential
      interaction of nontoxic doses of medications when injected simultaneously in the
      vitreous cavity, and disease processes that are now treated with these
      combination therapies.

PMID- 19857100
TI  - Prevention of selenite-induced cataractogenesis in Wistar albino rats by aqueous
      extract of garlic.
AB  - PURPOSE: The main aim of this study was to evaluate the inhibitory impacts of the
      aqueous extract of garlic (Ga) on the formation of cataract induced by sodium
      selenite (Se). METHODS: Thirty-two Wistar albino rat pups (4 equal groups: G1,
      G2, G3, and G4) were treated as follows: G1, subcutaneous (s.c.) and
      intraperitoneal (i.p.) injection of normal saline (0.3 mL) on postpartum (day
      10); G2, i.p. injection of aqueous extract of garlic (1 mL/kg body weight) and
      s.c. injection of normal saline (0.3 mL) on postpartum (day 10); G3, s.c.
      injection of sodium selenite (20 nmol/g body weight) and i.p. injection of normal
      saline (0.3 mL) on postpartum (day 10); and G4, s.c. injection of sodium selenite
      (20 nmol/g body weight) and i.p. injection of aqueous extract of garlic (1 mL/kg
      body weight) on postpartum (day 10). Daily i.p. injections of aqueous extract of
      garlic (in G2 and G4) and normal saline (in G1 and G3) were continued for 14
      days. The development of cataract was assessed over a period of 2 weeks after
      injection of sodium selenite. For further examination, the rats' lenses were
      removed and analyzed for glutathione (GSH), malondialdehyde (MDA) levels, and
      superoxide dismutase (SOD), glutathione peroxidase (GPX) activities. RESULTS: In
      G3 (Se-treated group), all rats developed grade 3 cataract in both eyes. However,
      in G1 (untreated control group), G2 (Ga-treated group), and G4 (Ga-Se-treated
      group), the lenses in both eyes of all rats remained clear (P < 0.0001). This
      clinical finding was associated with higher GSH level and GPX, SOD activities and
      lower level of MDA in the Se- and Ga-treated group (G4) compared with SS-treated
      group (G3) rat lenses (P < 0.003). CONCLUSIONS: Intraperitoneal injection of the
      Ga in rat model appeared to effectively prevent Se-induced cataract, thus such
      herbal remedy may be considered for treatment of cataract.

PMID- 19857101
TI  - Ocular hypotensive effects of anti-glaucoma agents in mice.
AB  - PURPOSE: To evaluate the ocular hypotensive effects induced by topical
      application of anti-glaucoma agents in mice. METHODS: Representative drugs
      (latanoprost and tafluprost [for prostanoid FP receptor agonists], timolol [for
      beta-adrenoceptor antagonists], dipivefrin [for alphabeta-adrenoceptor agonists],
      dorzolamide [for carbonic anhydrase inhibitors], pilocarpine [for muscarinic
      receptor agonists], bunazosin [for alpha(1)-adrenoceptor antagonists], or
      brimonidine [for alpha(2)-adrenoceptor agonists]) were used as anti-glaucoma
      agents; each one being topically applied once in a given male ddY mouse.
      Intraocular pressure (IOP) was measured using the microneedle method under
      general anesthesia. IOP was measured before, and at 1, 2, 3, and 4 h after
      administration of each drug. The contralateral eyes were untreated. At the each
      time point, the induced IOP reduction was evaluated by calculating the difference
      in IOP between the treated and untreated eyes in one and the same mouse. RESULTS:
      All of the evaluated anti-glaucoma agents reduced IOP in mice. The 2 prostanoid
      FP receptor agonists, the beta-adrenoceptor antagonist, and the alphabeta
      adrenoceptor agonist began significantly to reduce IOP 2 h after their
      administration, and mostly induced a long-lasting IOP reduction. The alpha(1)
      adrenoceptor antagonist, the alpha(2)-adrenoceptor agonist, the muscarinic
      receptor agonist, and the carbonic anhydrase inhibitor began reducing the IOP
      within 1 h after their administration, but their effects waned fairly quickly
      (the IOP reductions being lost by 3 h after their administration). Concomitant
      administration of timolol and tafluprost or of dorzolamide and tafluprost induced
      a significantly greater IOP reduction than that induced by either of the
      individual components. CONCLUSIONS: In this study, all the anti-glaucoma agents
      tested had apparent ocular hypotensive effects in mice. Our data suggest that the
      mouse may be a useful animal for the evaluation of the pharmacological effects of
      agents with various anti-glaucoma mechanisms, and for the evaluation of the
      enhanced ocular hypotensive effects that may be induced by the concomitant use of
      2 anti-glaucoma agents.

PMID- 19857102
TI  - Calpain inhibitor SNJ-1945 attenuates events prior to angiogenesis in cultured
      human retinal endothelial cells.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is an important regulator of
      angiogenesis and microvascular permeability. VEGF-induced cytoskeletal
      reorganization plays a crucial role in angiogenesis. Cytoskeletal organization in
      endothelial cells is regulated by calpain proteases (EC 3.4.22.17). Calpains are
      a family of 14 calcium-regulated, intracellular cysteine proteases, which
      modulate cellular functions by limited, specific proteolysis. Calpain 1 (mu
      calpain) and calpain 2 (m-calpain) are the 2 major typical calpain isoforms and
      are responsible for most calpain activity in endothelial cells. The purpose of
      the present study was to determine if an orally available form of calpain
      inhibitor, SNJ-1945, prevented angiogenesis induced by VEGF in cultured retinal
      endothelial cells. METHODS: Human retinal microvascular endothelial cells (HRMEC)
      were incubated with VEGF (60-100 ng/mL) for 24 h. Calcium uptake was measured
      with Fluo8. Total calpain activity was measured using fluorescent-labeled casein
      substrate, and separate activities for calpains 1 and 2 were assessed by casein
      zymography. Proteolysis of endogenous calpain substrate alpha-spectrin in situ
      was analyzed by immunoblotting. Angiogenesis in vitro was evaluated by measuring
      cell migration and tube formation into Matrigel. RESULTS: Incubation of HRMEC
      with VEGF resulted in calcium uptake, increased activity of mainly calpain 2, and
      increased calpain proteolysis of alpha-spectrin. Treatment of endothelial cells
      with calpain inhibitor SNJ-1945 reversed VEGF-mediated tube formation and cell
      motility. CONCLUSIONS: Inhibition of angiogenesis by specific calpain inhibitor
      in the presence of VEGF supported our hypothesis that calpains may be involved in
      VEGF-mediated angiogenesis in retinal endothelial cells. Therefore, manipulating
      calpain activity by calpain inhibitor SNJ-1945 might provide a promising therapy
      for management of pathological angiogenesis, such as that occurring in
      proliferative retinopathy and age-related macular degeneration with
      neovascularization.

PMID- 19857104
TI  - Safety of intracameral injection of gatifloxacin, levofloxacin on corneal
      endothelial structure and viability.
AB  - PURPOSE: To investigate the safety of intracameral injection of gatifloxacin,
      levofloxacin in a rabbit model as prophylaxis against endophthalmitis. METHODS:
      Twenty-four eyes of New Zealand white rabbits were randomly divided into 3
      treatment groups: levofloxacin, gatifloxacin, and balanced salt solution (BSS)
      control groups. After 100 microL of each was injected into the anterior chamber,
      endothelial toxicity was evaluated by measuring the central corneal thicknesses
      and the clinical toxicity scores using a slit-lamp at post-procedure days 3 and
      7. The percent of dead cells was determined by vital staining with alizarin red
      and trypan blue at 7 days after injection. Finally, in each group, scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM) were
      performed for the evaluation of structural integrity. RESULTS: The toxicity
      scores were increased at post-procedure days 3 and 7, but the difference among
      the groups was not statistically significant (P = 0.661, 0.216, respectively).
      With regard to baseline corneal thickness, only the levofloxacin group exhibited
      a significant increase from baseline (P = 0.028), whereas the other treatment
      groups showed no difference from baseline (P = 0.128 in gatifloxacin, 0.161 in
      BSS group). The mean corneal endothelial damage was 0.81 +/- 0.31% in the
      levofloxacin group, 0.56 +/- 0.47% in the gatifloxacin group, and 0.53 +/- 0.52%
      in the BSS group, with no statistically significant difference noted among the
      groups (P = 0.582). SEM revealed a well-preserved hexagonal endothelial cell
      mosaic and normal microvilli on the endothelial cell surface in the gatifloxacin
      and control groups. However, the levofloxacin group showed slightly disintegrated
      cellular borders. TEM revealed that each group maintained normal intracellular
      organization, whereas the levofloxacin group exhibited slightly flat cell
      configuration with irregular folds on the apical cell surface. CONCLUSIONS:
      Intracameral injection of gatifloxacin and levofloxacin was nontoxic in terms of
      clinical toxicity score, corneal thickness, and viability. However, there were
      changes on electron microscopy in the levofloxacin group, which may indicate
      microstructural damage to corneal endothelial cells.

PMID- 19857103
TI  - Evaluation of biomarkers of inflammation in response to benzalkonium chloride on
      corneal and conjunctival epithelial cells.
AB  - PURPOSE: Most eye drops contain preservatives; benzalkonium chloride (BAK) is
      most common. Recent data demonstrated BAK adding to toxicity. BAK is degraded
      into hydrogen peroxide (H(2)O(2)), which in even small amounts is known to be an
      irritant. Increased toxicity should cause localized inflammation with increased
      elaboration of inflammatory biomarkers. To evaluate the inflammation BAK causes
      to the ocular surface, enzyme linked immunosorbant assays (ELISAs) were utilized
      to quantify the levels of inflammatory biomarkers in response to BAK and/or
      H(2)O(2). METHODS: Immortalized human conjunctival and corneal epithelial cells
      were exposed to: BAK (0.001%-0.1%), hydrogen peroxide (H(2)O(2)) (0.01%-0.1%),
      and cell media for 1 h. Cytokine quantification was performed via enzyme-linked
      immunosorbent assays [ELISAs]). Additional experimentation was performed in which
      testing solutions were replaced with media after 1 h and the resulting
      supernatants quantified after 24 h. RESULTS: BAK induced significant amounts of
      interleukin (IL-) 1 and tumor necrosis factor (TNF), but only moderate amounts of
      C-reactive protein (CRP), IL- 10 and 12, and H(2)O(2). Lower concentrations of
      BAK induced proportionally less elaboration. Replacing the test solutions with
      media and providing 23 h for cytokine elaboration significantly increased TNF,
      but not IL-1. Lipopolysaccharide (LPS) positive controls induced substantial
      elaboration/release of both IL-1 and TNF as did in increasing the exposure to the
      full 24 h. CONCLUSIONS: After 1 h of exposure, BAK increased quantities of all
      biomarkers. The biomarkers in decreasing order of induction/upregulation were:
      TNF > or = IL-1 > or = IL-12 > or = IL-10 > or = CRP. Even low concentrations
      caused some degree of inflammation. Replacing the testing solution with media and
      providing 23 h for cytokine elaboration, significantly increased the
      elaboration/release of TNF, but not IL-1, as compared to the 1-h BAK exposure.
      Whereas increasing the exposure to the full 24 h by not removing the testing
      solution at the 1-h time point significantly increased the elaboration/release of
      both IL-1 and TNF.

PMID- 19857105
TI  - Ocular surface distribution and pharmacokinetics of a novel ophthalmic 1%
      azithromycin formulation.
AB  - PURPOSE: To investigate the ocular distribution of 1% azithromycin ophthalmic
      solution and the effect of polycarbophil-based mucoadhesive formulation on ocular
      tissue levels of azithromycin after single and multiple topical administrations
      in the rabbit eye. METHODS: Rabbits were treated with either a single
      administration of 1% azithromycin solution with or without polycarbophil, or with
      multiple administrations of 1% azithromycin solution in polycarbophil. Drug
      concentrations were measured using LC/MS/MS. Conjunctiva, cornea, aqueous humor,
      and tear samples were analyzed over a period of 144 h after a single
      administration of azithromycin with or without polycarbophil. Eyelid,
      conjunctiva, cornea, aqueous humor, and tear samples were collected over a period
      of 288 h during and after multiple administrations of azithromycin. RESULTS:
      Azithromycin was rapidly absorbed and distributed in the ocular tissues, reaching
      within 5 min, concentrations of 10,539 microg/mL in tear film, 108 microg/g in
      conjunctiva, and 40 microg/g in the cornea. The drug demonstrated tissue-specific
      half-lives of 15, 63, and 67 h, respectively. Following multiple administrations,
      the drug gradually accumulated. The polycarbophil formulation increased the
      bioavailability of the drug, producing peak concentrations that were between 5-
      and 12-fold higher than those without polycarbophil. Azithromycin also
      distributed rapidly in the eyelids, reaching peak concentrations of 180 mug/g at
      the end of the 7-day treatment, and was eliminated with a half-life of 125 h. Six
      days after treatment was discontinued, eyelid levels of azithromycin were above
      40 microg/g. CONCLUSIONS: Sustained and high concentrations were encountered with
      7-day approved administration of 1% azithromycin formulation (AzaSite, Inspire
      Pharmaceuticals, Inc., Durham, NC) within all ocular surface tissues,
      particularly the lids. Many ocular surface disorders involving the tear film,
      eyelids, and adnexal structures are associated with chronic, low-grade bacterial
      infection and may potentially lead to decreased vision secondary to corneal
      scarring. Various topical antibiotic and steroid combinations with or without
      oral tetracyclines are commonly used with variable clinical response and known
      potential side effects. The clinical relevance of this study is unknown; however,
      the long-lasting antibacterial and additional anti-inflammatory properties of
      topical azithromycin might offer an effective alternative treatment option and
      should be explored further in clinical studies.

PMID- 19857106
TI  - Intraocular pressure (IOP) reduction by latanoprost in Japanese normal tension
      glaucoma patients over a five-year period stratified by presenting IOP.
AB  - PURPOSE: We examined the effectiveness of latanoprost for reducing intraocular
      pressure (IOP) in Japanese patients with normal tension glaucoma (NTG) over a 5
      year period. DESIGN: Prospective interventional case series. The patients were
      classified into 2 groups based on mean IOP. METHODS: A total of 38 patients with
      NTG were studied after being classified into the high-tension (mean IOP 16 mmHg
      or greater, n = 27) and low-tension (mean IOP lower than 15 mmHg, n = 11) groups.
      IOP was measured and Humphrey Field Analyzer (HFA) examinations were conducted at
      6, 12, 24, 36, 48, and 60 months after beginning a daily administration of
      latanoprost. RESULTS: Mean IOP before administration was 17.6 mmHg in the high
      tension group, which was reduced to 13.9, 14.6, 14.4, 14.1, 13.6, and 14.6 mmHg
      at 6, 12, 24, 36, 48, and 60 months, respectively, after beginning
      administration. That in the low-tension group was 13.6 mmHg before
      administration, and then was reduced to 12.2, 11.4, 11.5, 12.5, 10.5, and 11.5
      mmHg, respectively, after beginning administration was noted. Mean deviation (MD)
      values in the HFA examinations were reduced by -4.27 and -1.49 dB after 5 years
      in the high- and low-tension groups, respectively. CONCLUSIONS: Latanoprost
      administration was effective in reducing IOP over a 5-year period in a range of
      3.1-4.1 and 1.3-3.6 mmHg in NTG patients with high- and low-tension levels,
      respectively. In addition, our results indicate that latanoprost helped to
      prevent a decrease in MD values in both groups, as shown by the results of HFA
      examinations.

PMID- 19857107
TI  - Intravitreal bevacizumab for neovascular glaucoma.
AB  - PURPOSE: To report 6-month and 1 year outcomes of eyes treated for neovascular
      glaucoma (NVG) with intravitreal bevacizumab injection and panretinal laser (PRP)
      compared to those receiving PRP alone. DESIGN: retrospective, consecutive case
      series. METHODS: Charts of patients with NVG from retinal ischemia and at least 6
      months of follow-up were reviewed. Patients were treated with one injection of
      1.25 mg intravitreal bevacizumab followed by PRP or with PRP alone. The primary
      outcome was the long-term angle anatomy. Secondary measures included intraocular
      pressure (IOP), visual acuity, patient compliance, and control of systemic
      diseases. RESULTS: Fourteen eyes of 12 patients treated with bevacizumab and PRP
      and 15 eyes of 11 patients treated with PRP alone were included in the study.
      Mean sectors of open angle at baseline was 1.31 in the bevacizumab group and 1.47
      in the retinal ablation group (P = 0.73). Mean sectors of open angle was 2.14 and
      1.18 in the bevacizumab and retinal ablation groups, respectively (P < 0.05) at 6
      month follow-up, and 2.27 and 1.18, respectively (P < 0.05) at 1-year follow-up.
      Mean baseline IOP was 32.3 mmHg (+/-14.8) in the bevacizumab group and 31.8 mmHg
      (+/-13) in the PRP group (P = 0.75). At 6-month follow-up, the mean IOP was 18.28
      mmHg (+/-10) in the bevacizumab group and 23.33 mmHg (+/-14.6) in the PRP group
      (P = 0.05), and 19.12 mmHg (+/-6.8) and 26.2 mmHg (+/-18) (P = 0.1), respectively
      at 1-year follow-up. Nineteen patients were judged to be noncompliant, 10 had
      uncontrolled diabetes and 7 had uncontrolled hypertension. CONCLUSIONS: This
      study documents better long-term preservation of open angle and IOP control in
      eyes receiving bevacizumab along with PRP. We stress that NVG is still associated
      with poor visual acuity outcomes.

PMID- 19857108
TI  - Central corneal thickness during treatment with travoprost 0.004% in glaucoma
      patients.
AB  - PURPOSE: Experimental studies demonstrated an alteration of corneal collagen
      structure by prostaglandin analogues. The possible effect of the prostaglandin
      F(2alpha) analogue travoprost 0.004% on the central corneal thickness (CCT) in
      newly diagnosed glaucoma patients was evaluated. METHODS: Consecutive,
      interventional case series. Seventy-four patients/136 eyes with glaucoma were
      included in the statistical analysis. All patients received travoprost 0.004%
      (Travatan(R)) once daily in one or both eyes. CCT was measured by using
      noncontact optical low-coherence reflectometry prior to the treatment and after 6
      and 12 months. RESULTS: Mean CCT of all treated eyes (n = 136) was 546.71 +/-
      34.63 mum at baseline, 535.14 +/- 34.78 mum after 6 months, and 532.38 +/- 34.18
      mum after 12 months (ANOVA, P < 0.001). Ninety-five percent of all treated eyes
      showed a decrease of CCT. CCT reduction mainly developed within the first 6
      months of the treatment period. After 12 months, a CCT reduction >30 mum occurred
      in 5.1% of all treated eyes. There was a significant correlation between the
      magnitude of corneal thinning and the initial CCT but not between corneal
      thinning and IOP reductions. CONCLUSIONS: Topical therapy with the prostaglandin
      derivate travoprost is accompanied by a significant reduction of CCT within one
      year of treatment. Further clinical studies are needed to evaluate the possible
      long-term effects of prostaglandins on the CCT of glaucoma patients.

PMID- 19857109
TI  - Cataract surgery under infliximab therapy in a patient with Behcet's disease.
AB  - PURPOSE: To report a case of a successful cataract surgery outcome in a patient
      with Behcet's disease (BD) without postoperative inflammation under infliximab
      therapy. CASE: A 40-year-old man who had frequent episodes of hypopyon uveitis
      despite immunosuppressive therapy underwent cataract surgery. Infliximab (5
      mg/kg) was given intravenously to prevent inflammation during the perioperative
      period. After the initial administration, infliximab was given at 2 and 6 weeks,
      and then it was given at 8 weeks intervals thereafter. The patient underwent
      cataract surgery in both eyes at the midpoint of the 8 weeks duration schedule
      with an uneventful postoperative clinical course for up to 12 months except for
      the contraction of the anterior capsule in both eyes and posterior capsule
      opacification in 1 eye. CONCLUSIONS: Infliximab therapy may be effective when
      performing cataract surgery on BD patients who have uncontrollable uveitis.

PMID- 19857110
TI  - Bilateral deepening of upper lid sulcus from topical bimatoprost therapy.
AB  - PURPOSE: To report a new adverse effect related to treatment with bimatoprost.
      METHOD: Case report. A 43-year-old Asian female with bilateral glaucoma was
      noticed to have bilateral deepening of upper lid sulcus 3 months after beginning
      treatment with bimatoprost 0.03%. RESULTS: Bimatoprost was discontinued due to
      cosmetic reasons, and there was improvement of the lid sulcus deepening
      bilaterally 4 weeks after stopping the drug. CONCLUSIONS: Deepening of upper lid
      sulcus is one of the adverse effects related to treatment with bimatoprost. This
      effect may be more prominent in Asians who have relatively full upper lid sulcus.

PMID- 19857111
TI  - Isolation of BNYVV coat protein-specific single chain Fv from a mouse phage
      library antibody.
AB  - Beet necrotic yellow vein virus (BNYVV) infects sugar beet plants worldwide and
      is responsible for the rhizomania disease and severe economic losses. Disease
      severity and lack of naturally occurring resistant plants make it very difficult
      to control the virus, both from epidemiological and economic standpoints.
      Therefore, early detection is vital to impose hygiene restrictions and prevent
      further spread of the virus in the field. Immunoassays are one of the most
      popular methodologies for the primary identification of plant pathogens including
      BNYVV since they are robust, sensitive, fast, and inexpensive. In this study, the
      major coat protein (CP21) of BNYVV was cloned and expressed in Escherichia coli.
      Thereafter, mice were immunized with purified CP21 and a phage antibody library
      was constructed from their PCR-amplified immunoglobulin repertoire. Following
      filamentous phage rescue of the library and four rounds of panning against
      recombinant CP21 antigen, several specific single chain Fv fragments were
      isolated and characterized. This approach may pave the way to develop novel
      immunoassays for a rapid detection of viral infection. Moreover, it will likely
      provide essential tools to establish antibody-mediated resistant transgenic
      technology in sugar beet plants.

PMID- 19857112
TI  - Characterization of the epitope region of F1-2 and F1-5, two monoclonal
      antibodies to Botulinum neurotoxin type A.
AB  - F1-2 and F1-5 are mouse IgG1 monoclonal antibodies that bind the heavy chain of
      Botulinum neurotoxin serotype A (BoNT/A). To characterize the epitopes of F1-2
      and F1-5, three complementary experimental approaches were selected. First,
      recombinant peptide fragments of BoNT/A heavy-chain were used in Western blots to
      identify the epitope regions. Second, a peptide phage display library was used to
      identify specific amino acids bound by F1-2 and F1-5, and these amino acids were
      mapped onto the three-dimensional structure of BoNT/A. Third, selected amino
      acids were mutated to alanine and the effects of the mutations on F1-2 and F1-5
      binding were evaluated. Data from recombinant peptide fragment binding
      experiments suggested that the epitopes for antibodies F1-2 and F1-5 are located
      between amino acids R564 and S793 on the toxin heavy chain. Furthermore,
      elimination of amino acids from the amino terminus (R564-K595), or from the
      carboxyl terminus (N759-S793) of this fragment abolished binding of both F1-2 and
      F1-5, suggesting a conformational epitope for these antibodies. Peptide sequences
      deduced from antibody binding to the peptide phage display library suggested that
      tyrosine residues located at positions 748, 750, and 753 might form a significant
      part of the F1-2 and F1-5 epitope motif. Mutation of Y750 or Y753 to alanine
      significantly reduced binding of either antibody, while mutation of Y748 to
      alanine had no effect on antibody binding. The nucleotide and deduced amino acid
      sequences of the variable regions of the heavy chains of F1-2 and F1-5 are
      reported. The complementarity determining regions (CDRs) of the heavy chains were
      found to be 78% identical. It is possible that F1-2 and F1-5 bind the same
      epitope via the common amino acids within their CDRs.

PMID- 19857113
TI  - Phage displayed scFv: pIII scaffold may fine tune binding specificity.
AB  - The fine specificity of antibodies is important for their discriminating powers
      during diagnostics and in vivo therapy. We have attempted to isolate human scFv
      antibodies to the oncofetal antigen, the placental isozyme of alkaline
      phosphatase (PLAP) in which it is important to distinguish between the closely
      related intestinal alkaline phosphatase (IAP) and bone alkaline phosphatase (BAP)
      isozymes. As the antibodies are selected in the phage displayed form and might be
      finally used as different entities, including the soluble scFv form, it may be
      important to look at the influence of scaffolds in determining specificity. There
      have been earlier reports of the role of the constant region and other
      scaffolding proteins in determining specificity. In this paper, we report
      isolation of one such clone, E6, which showed specificity to PLAP in phage
      antibody form but lost the specificity when soluble scFv was tested for same, and
      showed partial cross reactivity to BAP. We suggest that the altered specificity
      of scFv might be the result of loss of phage pIII scaffold, which is present in
      phage-displayed antibody and may help the displayed antibody to assume specific
      conformational structure, which may govern binding characteristics of the same.

PMID- 19857114
TI  - Activation signal transduction by proline-rich tyrosine kinase 2 (PYK2) in
      peripheral blood mononuclear cells from patients with systemic lupus
      erythematosus.
AB  - To explore the role of proline-rich tyrosine kinase 2 (PYK2) in systemic lupus
      erythematosus (SLE), we studied the expression, activation, and function of PYK2
      in peripheral blood mononuclear cells (PBMC) from 36 SLE patients. As controls,
      samples from 19 patients with rheumatoid arthritis and 15 healthy individuals
      were studied simultaneously. We found a significant increase of both the total
      PYK2 protein and its activated/phosphorylated form in PBMCs from patients with
      SLE, particularly those with the complication of nephritis (WHO class IV). There
      is a clear correlation between the activation of PYK2 and the level of serum
      complements. In active SLE patients, activation of PYK2 in PBMCs accompanies the
      increased cell proliferation and the induced expression of co-stimulatory
      molecules CD40L and CTLA4. These results indicate that phosphorylated PYK2 may
      induce the expression of CD40L and CTLA4, and subsequently the cell
      proliferation. PYK2 signaling enhances the autoreactive lymphocyte activation and
      plays an important role in the pathogenesis of SLE.

PMID- 19857115
TI  - Construction and selection of human Fab antibody phage display library of liver
      cancer.
AB  - The aim of this study was to construct the fully humanized anti-hepatoma Fab
      fragment phage libraries and select antibodies against hepatoma specifically.
      PBMCs of liver cancer patients were immunized in vitro with HpeG(2) cells and
      were then transformed by Epstein-Barr virus (EBV). After total RNA was extracted,
      the heavy chain Fd and kappa/lambda light chain were amplified by RT-PCR and
      cloned into the vector pComb3 to construct the libraries of Fab fragments. The
      libraries were then panned by HpeG(2) cells. By means of ELISA and
      immunochemistry, the Fab phage antibodies binding with hepatoma were selected and
      identified. The Fd and light chain PCR products were subsequently inserted into
      pComb3, and the volume of Fab libraries reached 1.7 x 10(7). The libraries were
      enriched about 138-fold by three cycles of panning. 540 phage clones were picked
      randomly. Using cell ELISA and immunohistochemistry with cultured cells, one
      clone Fab phage antibody, which had binding activity with hepatoma, was picked
      out. Fully humanized anti-hepatoma Fab antibody phage display libraries were
      constructed. One phage clone was selected and confirmed to specifically bind to
      hepatoma cells. The selected Fab antibody may be further developed and applied to
      clinical diagnosis and therapy.

PMID- 19857116
TI  - Preparation and characterization of a monoclonal antibody with high affinity for
      soluble Abeta oligomers.
AB  - Amyloid beta-protein (Abeta) has been causally implicated in the
      neurodegenerative processes that accompany Alzheimer's disease. Soluble oligomers
      of the Abeta(1-42) fragment are thought to be significantly more neurotoxic than
      higher molecular weight aggregates. We report the isolation and characterization
      of a mouse monoclonal antibody (MAb) directed against soluble Abeta(1-42)
      oligomers. Synthetic Abeta(1-42) oligomers were assembled in vitro; these were
      used to immunize mice, and hybridomas were isolated following myeloma fusion of
      splenocytes from immunized animals. Screening for reactivity against Abeta(1-42)
      resulted in the identification of MAb A8 with high affinity for soluble
      oligomers. The isotype of A8 was found to be IgG(2b). Experiments using sub
      peptides of Abeta(1-42) revealed that the epitope identified by A8 lies within
      the 1-6 region of Abeta. The antibody displays high affinity for soluble Abeta(1
      42) oligomers in the molecular weight range of 16.5-25 kDa, and detected target
      antigen in brain sections from senescence-accelerated SAMP 8 mice. The
      sensitivity and optimal titers for the detection of soluble Abeta(1-42) oligomers
      were determined to be 0.625 microg/mL in indirect ELISA, and 1:10(6), 1:4000, and
      1:150 for ELISA, Western blotting, and immunohistochemistry, respectively. The A8
      antibody specific for soluble Abeta(1-42) oligomers will provide a valuable tool
      for Alzheimer's disease research.

PMID- 19857117
TI  - Monoclonal antibodies against the connexin43-interacting protein CIP85.
AB  - The connexin43 (Cx43)-interacting protein of 85 kDa CIP85 has been identified as
      an interacting partner for the cytoplasmically located, carboxyl-terminal tail of
      Cx43. Further characterization has shown that the interaction between Cx43 and
      CIP85 is associated with increased turnover of Cx43 that may be lysosome
      mediated. This suggests that CIP85 may regulate the endocytic trafficking of Cx43
      from the plasma membrane and its degradation, and thus, indirectly influence gap
      junction function. This study reports the first successful production of
      monoclonal antibodies (MAbs) against CIP85. These antibodies are useful in
      detecting CIP85 expressed in several species in immunoblotting,
      immunoprecipitation, and immunofluorescence microscopy experiments. These MAbs
      will assist in defining the functional roles of CIP85, including its influence on
      Cx43 trafficking and intercellular communication through Cx43-containing gap
      junctions.

PMID- 19857118
TI  - Novel immunohistochemical monoclonal antibody against rat B cell receptor
      Associated Protein 31 (BAP31).
AB  - BAP31 is an evolutionarily conserved polytopic integral protein of the
      endoplasmic reticulum (ER) membrane implicated in regulating the export of
      selected membrane proteins from the ER to downstream compartments of the
      secretory pathway. BAP31 interacts with mIgD, cellubrevin, major
      histocompatibility complex class I, and BCL-2/BCL-X(L) and plays an important
      role in regulating the egress of these proteins and in apoptosis. Although BAP31
      RNA is ubiquitous, the protein's anatomic localization in rat tissues has not
      been determined. This is partially because production of high affinity
      antibodies, especially monoclonal antibodies (MAbs) suitable for
      immunohistochemical staining, has lagged. To gain further insight into its
      possible functions, we generated a novel MAb specific for rat BAP31 in
      immunocytochemistry and immunohistochemistry and localized BAP31 in some rat
      tissues. Immunoreactivity of BAP31 was prominent in fundic glands, colon,
      pancreatic acinuses, and liver but not in skeleton muscle and lung. Thus,
      successful production of rat BAP31 monoclonal antibodies provides a new powerful
      tool for investigation of BAP31 function in the rat model.

PMID- 19857119
TI  - Generation of monoclonal antibodies to surface proteins of human multiple myeloma
      employing membrane extracts for murine in vivo immunizations.
AB  - Multiple myeloma is a malignancy of plasma cells that accounts for 1% of cancers
      worldwide and is treatable, yet incurable. U266 is an IgE-secreting, IL-6
      producing human multiple myeloma cell line, against whose unique surface markers
      we have tried to raise monoclonal antibodies (MAbs). Female Balb/c mice (6 weeks
      old) were immunized through two routes of administration, with three different
      antigenic concentrations. Fusion efficiencies and specific efficiencies for the
      three antigenic concentrations were calculated. It was found that while an
      initial immunogen concentration of 10 microg gave the best fusion efficiency of
      63.89%, an initial immunogen concentration of 15 microg resulted in the best
      specific efficiency of 54.54%. Out of the 147 supernatants selected for
      screening, 66 were found reactive to common surface proteins of non-malignant
      human plasma cells and seven were myeloma-specific MAbs. These MAbs have a range
      of potential applications in multiple myeloma imaging, phenotyping, and possible
      targeted therapy.

PMID- 19857120
TI  - A novel monoclonal antibody specific to peptide pdnaelvlltlgqawqg.
AB  - Cis-aconitic acid decarboxylase (CAD) has been assumed to be a key enzyme in the
      production of itaconic acid. Here we aimed to efficiently generate the monoclonal
      antibody against the CAD protein. We synthesized the peptide "pdnaelvlltlgqawqg"
      based on the published CAD cDNA sequences. The peptide was chemically linked with
      the carrier protein keyhole limpet hemocyanin and then injected into Balb/c mice.
      Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA)
      using either purified 6 x His-CAD fusion protein or the peptide. One MAb named K2
      (IgG1), effective in detecting the native CAD protein, was characterized by ELISA
      and Western immunoblotting. By using the MAb, we found that the CAD protein was
      more highly expressed in poorly differentiated gastric cancer tissues than in
      well-differentiated and moderately differentiated tissues. Taken together, the
      MAb K2 would be helpful for understanding the functions of CAD in gastric
      carcinogenesis.

PMID- 19857127
TI  - Highlights from the November 2009 issue of DNA and cell biology.

PMID- 19857121
TI  - Production and characterization of monoclonal antibodies to human sclerostin.
AB  - We developed and characterized monoclonal antibodies directed against the amino
      terminal and carboxy-terminal regions of human and mouse sclerostin (scl). Amino
      terminal and carboxy-terminal scl peptides with limited homology to scl domain
      containing protein-1 were synthesized using f-moc chemistry. The peptides were
      conjugated to keyhole limpet hemocyanin and the conjugates were used for
      immunization of mice. Monoclonal antibodies were obtained and characterized using
      bacterially expressed and insect cell-expressed recombinant scl. The amino
      terminal (IgG 2aK) and carboxy-terminal (IgG 2bK) antibodies bound bioactive
      sclerostin that was expressed in an insect-cell expression system with
      dissociation constants in the nanomolar range. The antibodies are potentially
      useful agents that can be used for modulating sclerostin bioactivity.

PMID- 19857128
TI  - 23S rRNA mutation A2074C conferring high-level macrolide resistance and fitness
      cost in Campylobacter jejuni.
AB  - To examine the development of macrolide resistance in Campylobacter jejuni and
      assess the fitness of the macrolide-resistant mutants, two macrolide-susceptible
      C. jejuni strains, American Type Culture Collection (ATCC) 33291 and H1, from
      different geographic areas were exposed to tylosin in vitro. Multiple mutant
      strains were obtained from the selection. Most of the high-level macrolide
      resistant strains derived from the selection exhibited the A2074C transversion in
      all three copies of 23S rRNA and displayed strong stability in the absence of
      antibiotic selection pressure. The competition experiments demonstrated that the
      strains containing the A2074C transversion imposed a fitness cost in competition
      mixtures. In addition, the fitness cost of the mutation was not ameliorated after
      approximately 500 generations of evolution under laboratory conditions. These
      findings indicate that the A2074C transversion in C. jejuni is not only
      correlated with stable and high-level macrolide resistance but also associated
      with a fitness cost.

PMID- 19857129
TI  - Daptomycin activity tested against linezolid-nonsusceptible gram-positive
      clinical isolates.
AB  - Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus spp.
      represent the most frequently recovered organisms from bloodstream infections. As
      a treatment option, daptomycin has been recently approved for the treatment of S.
      aureus bacteremia and right-sided endocarditis. We evaluated the spectrum of
      activity and potency of daptomycin and other antibiotics against 142 linezolid
      nonsusceptible clinical strains. The isolates were tested for susceptibility by
      reference broth microdilution methods utilizing physiologic free calcium ions
      levels (50 mg/L) when testing daptomycin. Staphylococcus spp. and Enterococcus
      spp. were selected and screened for 23S rRNA, L4 and L22 mutations, and the cfr
      gene. Daptomycin was potent against all linezolid-nonsusceptible staphylococci
      (minimal inhibitory concentrations [MIC](90), 0.5 microg/ml) and enterococci
      (MIC(90), 1 microg/ml) isolates at the respective breakpoints of <or=1 microg/ml
      and <or=4 microg/ml. The majority of the isolates (84.5%) showed ribosomal target
      site alterations, mainly G2576T, and five isolates (two S. aureus and three
      Staphylococcus epidermidis) had the mobile cfr element. In conclusion, daptomycin
      was the most active agent tested against this collection of gram-positive
      clinical organisms and ribosomal target mutations comprised the main resistance
      mechanism against linezolid.

PMID- 19857130
TI  - Mycobacterium tuberculosis genotypic diversity in pyrazinamide-resistant isolates
      of Iran.
AB  - Pyrazinamide (PZA) is an important first-line drug used for the short-course
      treatment of tuberculosis in combination with isoniazid and rifampin. It has been
      reported that mutations in pncA gene correlate well with PZA resistance depending
      on the geographic area. On the other hand, different genotypes of Mycobacterium
      tuberculosis show different affinities to acquire resistance-related mutations.
      To determine the relative significance of various mutations in the pncA gene in
      Iranian PZA-resistant M. tuberculosis isolates and to analyze the association of
      different genotypes of M. tuberculosis with PZA resistance, 34 PZA-resistant M.
      tuberculosis isolates were analyzed for their pncA mutations using direct
      sequencing. These isolates were genotyped by IS6110 fingerprinting and
      spoligotyping methods. Mutations in the pncA gene were identified in 24 of 34 of
      these isolates (70.58%). No mutations were found in 10 PZA-resistant isolates,
      which implied that alternative mechanisms of resistance existed in these strains.
      PZA resistance was strongly (41.2%) associated with multidrug-resistant
      tuberculosis. Genotyping revealed the Central Asian (CAS) and East-African Indian
      families as the most prevalent families between PZA-monoresistant isolates versus
      the Beijing and Haarlem families which were the most frequent families between
      PZA including multidrug-resistant isolates.

PMID- 19857131
TI  - Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in a newly
      established Greek hospital.
AB  - One hundred and sixty-four Acinetobacter baumannii isolates, collected from
      patients hospitalized in a newly established hospital in Northern Greece during
      the 8-year period (2001-2008) of its operation, were tested for the presence of
      Ambler class A and D carbapenemases and typed by random amplified polymorphic DNA
      and pulsed-field gel electrophoresis. Isolates were clustered into five distinct
      clones. The majority of isolates were carrying the bla(OXA-58) gene, while a new
      clone emerged in 2008.

PMID- 19857132
TI  - The impact of the pneumococcal conjugate vaccine on antimicrobial resistance in
      the United States since 1996: evidence for a significant rebound by 2007 in many
      classes of antibiotics.
AB  - BACKGROUND: The impact of the introduction of the pneumococcal conjugate vaccine
      over antimicrobial resistance has not been well established. The present study
      models the changes in resistance over time for all major classes of antibiotics.
      METHODS: Susceptibility data on a total of 129,652 isolates from The Surveillance
      Network surveillance database during the period 1996-2007 were available for
      analysis, as well as age, specimen source, inpatient or outpatient location, and
      census region. Cubic splines in a logistic regression mixed model were used to
      model changes of the resistance rates over time in the United States, taking into
      account risk factors, so that separate adjusted curves were modeled for each
      antibiotic. RESULTS: Yearly resistance prevalence to most antibiotics had been
      increasing in the period 1996-2001. Adjusted prevalence rates in a multivariate
      model declined in the period 2001-2004 for penicillin, erythromycin,
      amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, tetracycline,
      ceftriaxone, and multidrug. These same antibiotics showed a significant rebound
      for the period 2004-2007, with the largest overall increase for erythromycin,
      followed by amoxicillin/clavulanate, tetracycline, multidrug, penicillin,
      trimethoprim/sulfamethoxazole, and ceftriaxone. Changes in both decline and
      rebound were more marked for children <5 years old and for otitis media isolates.
      CONCLUSION: The indirect effect of the pneumococcal conjugate vaccine
      introduction on yearly resistance prevalence for several antibacterials as well
      as for multidrug resistance is one of blunting of a prior sustained increase,
      with a significant but short-lived decrease in resistance rates, and a
      significant rebound in adjusted rates for the period 2004-2007.

PMID- 19857133
TI  - Streptococcus pneumoniae nasopharyngeal carriage in children attending day-care
      centers in the central region of Portugal, in the era of 7-valent pneumococcal
      conjugate vaccine.
AB  - The 7-valent pneumococcal conjugate vaccine became available in Portugal in 2001.
      Although not included in the national immunization program, vaccination coverage
      is high (over 60%). We studied for the first time the rates of nasopharyngeal
      (NP) carriage of pneumococci, antibiotic resistance patterns and serotypes among
      children attending day-care centers (DCCs) in Coimbra, a city in the Central
      Region of Portugal. Between January and February 2007, a cross-sectional study
      was conducted among children aged 6 months to 6 years attending eight DCCs. NP
      swabs were obtained from 507 children: 76.7% had received at least one dose of 7
      valent pneumococcal conjugate vaccine and 64.3% were age-appropriately
      vaccinated. The global pneumococcal carriage rate was 61.3%. Colonization
      proportions varied with age and number of children attending each DCC. Serotyping
      revealed that 20.7% of the pneumococci were vaccine types (VTs), 70.8% were non
      VTs, and 8.5% were nontypeable. Serotype 19F was the second most frequent
      serotype being detected in 10.5% of the samples. While global NP carriage was not
      associated with vaccination status, non-VTs were predominant among vaccinated
      children, who had significantly lower prevalence of VT. Of all isolates, 15.7%
      had penicillin minimum inhibitory concentrations that ranged between 0.12 and 2
      microg/ml. The proportion of resistant strains was significantly higher among VT
      and unvaccinated children. In conclusion, the rates of vaccination and prevalence
      of pneumococcal NP were high. Rates of antimicrobial resistance were similar to
      those found in studies conducted in Oeiras and Lisbon. This study is a platform
      for future surveillance activities.

PMID- 19857134
TI  - Molecular epidemiology and genetic environment of acquired bla ACC-1 in
      Salmonella enterica serotype Livingstone causing a large nosocomial outbreak in
      Tunisia.
AB  - Eighty-four isolates of Salmonella enterica serovar Livingstone were collected
      from patients hospitalized in a pediatric ward in Sfax Hospital (South Tunisia).
      These isolates were responsible for two nosocomial outbreaks in 2000 and 2002.
      Twenty-eight clinical isolates of S. enterica serovar Livingstone were also
      obtained in two other Tunisian hospitals in Monastir (Central Tunisia) and Tunis
      (North Tunisia), respectively, in 2002 and 2003. Pulsed-field gel electrophoresis
      yielded that these isolates were closely related. Antimicrobial susceptibility
      testing showed a particular beta-lactam resistance phenotype, suggestive of the
      presence of an AmpC-type enzyme in 111 of the 112 clinical isolates. bla(ACC-1)
      was characterized by polymerase chain reaction (PCR) and sequence analysis in the
      111 isolates. TEM-1 was characterized in all strains and SHV-2a in only two
      strains. The genetic organization of bla(ACC-1) was determined by PCR mapping and
      sequencing. The plasmid-borne bla(ACC-1) gene mapped immediately downstream from
      ISEcp1. This ISEcp1 insertion sequence was itself disrupted by IS26 insertion
      sequences. A supplementary deletion of 13 bp was observed in ISEcp1 upstream
      IS26, in all isolates from Tunis, except one. PCR analysis and sequencing also
      revealed the presence of tnpR, bla(SCO-1), gdha, IS1353, and TniB Delta 1.

PMID- 19857135
TI  - Molecular epidemiologic analysis of Enterococcus faecalis isolates in Cuba by
      multilocus sequence typing.
AB  - We carried out the first study of Enterococcus faecalis clinical isolates in Cuba
      by multilocus sequence typing linking the molecular typing data with the presence
      of virulence determinants and the antibiotic resistance genes. A total of 23 E.
      faecalis isolates recovered from several clinic sources and geographic areas of
      Cuba during a period between 2000 and 2005 were typed by multilocus sequence
      typing. Thirteen sequence types (STs) including five novel STs were identified,
      and the ST 64 (clonal complex [CC] 8), ST 6 (CC2), ST 21(CC21), and ST 16 (CC58)
      were found in more than one strain. Sixty-seven percent of STs corresponded to
      STs reported previously in Spain, Poland, and The Netherlands, and other STs
      (ST115, ST64, ST6, and ST40) were genetically close to those detected in the
      United States. Prevalence of both antimicrobial resistance genes [aac(6')
      aph(2''), aph(3'), ant(6), ant(3'')(9), aph(2'')-Id, aph(2'')-Ic, erm(B), erm(A),
      erm(C), mef(A), tet(M), and tet(L)] and virulence genes (agg, gelE, cylA, esp,
      ccf, and efaAfs) were examined by polymerase chain reaction. Aminoglycoside
      resistance genes aac(6')-Ie-aph(2'')-Ia, aph(3'), ant(6), ant(3'')(9) were more
      frequently detected in ST6, ST16, ST23, ST64, and ST115. The multidrug resistance
      was distributed to all STs detected, except for ST117 and singleton ST225. The
      presence of cyl gene was specifically linked to the ST64 and ST16. Presence of
      the esp, gel, and agg genes was not specific to any particular ST. This research
      provided the first insight into the population structure of E. faecalis in Cuba,
      that is, most Cuban strains were related to European strains, whereas others to
      U.S. strains. The CC2, CC21, and CC8, three of the biggest CCs in the world, were
      evidently circulating in Cuba, associated with multidrug resistance and virulence
      traits.

PMID- 19857136
TI  - Emergence of SHV-2a extended-spectrum beta-lactamases in clinical isolates of
      Pseudomonas aeruginosa in a university hospital in Tunisia.
AB  - Extended-spectrum beta-lactamases (ESBLs) in Pseudomonas aeruginosa are
      increasingly reported worldwide. In our study, a total of 70 clinical isolates of
      multidrug-resistant P. aeruginosa were studied. Isoelectric focusing
      electrophoresis, PCR, and PCR product sequencing were designed to characterize
      the contained ESBLs. The Double Disk Synergy Test in Cloxacillin (250 microg/ml)
      containing Mueller-Hinton agar plates with a 20 mm distance between disks was the
      most reliable ESBL-screening method. Seven out of 70 multidrug-resistant P.
      aeruginosa clinical isolates were positive for ESBL and have the bla(SHV-2a) ESBL
      gene. The bla(SHV-2a)-positive isolates were clonally related according to
      Enterobacterial Repetetive Intergenic Consensus-PCR (ERIC-PCR) results. The
      bla(SHV-2a) gene was found to be chromosomally located, and the flanking IS26
      sequence in the immediate upstream region of the bla(SHV-2a) gene was detected in
      all SHV-2a-producing isolates. This is the first report of SHV-2a-producing P.
      aeruginosa isolates from Tunisia.

PMID- 19857137
TI  - Clonal composition of Escherichia coli causing community-acquired urinary tract
      infections in the State of Rio de Janeiro, Brazil.
AB  - Recent studies from North America and Europe have demonstrated community-wide
      clonal spread of uropathogenic Escherichia coli (UPEC). To investigate if a
      similar pattern of spread occurs in Brazil, we characterized UPEC from women with
      community-acquired urinary tract infection (UTI) in Rio de Janeiro. E. coli
      isolates from women with UTI in one public outpatient clinic were evaluated for
      antibiotic susceptibility, E. coli phylogenetic grouping, enterobacterial
      repetitive intergenic consensus (ERIC) 2 PCR and pulsed-field gel electrophoresis
      fingerprinting, and multilocus sequence typing. From March 2005 to November 2006,
      344 patients were studied. Of these, 186 (54%) had confirmed UTI, 118 (63.4%) of
      which were caused by E. coli. More than 50% of these isolates were resistant to
      ampicillin and trimethoprim/sulfamethoxazole. Of these, 96 (81%) belonged to 19
      ERIC2 clonal groups. The largest group included 15 isolates, all belonging to
      multilocus sequence typing group ST69 and phylogenetic group D; they had pulsed
      field gel electrophoresis patterns sharing at least 89% similarity compared with
      the CgA reference strain ATCC BAA-457. CgA strains have been found to be
      widespread in the United States in the early 2000s. Clonal group E. coli strains
      accounted for a large proportion (52%) of all UTIs and 82% of the
      trimethoprim/sulfamethoxazole-resistant E. coli UTIs. Thus, as in North America
      and Europe, UPECs that cause UTI in Rio de Janeiro also show clonal distribution,
      and a substantial proportion of drug-resistant UTI is caused by a small set of
      genetically related E. coli strains.

PMID- 19857138
TI  - Antibiotic resistance genes in the vaginal microbiota of primates not normally
      exposed to antibiotics.
AB  - Previous studies of resistance gene ecology have focused primarily on populations
      such as hospital patients and farm animals that are regularly exposed to
      antibiotics. Also, these studies have tended to focus on numerically minor
      populations such as enterics or enterococci. We report here a cultivation
      independent approach that allowed us to assess the presence of antibiotic
      resistance genes in the numerically predominant populations of the vaginal
      microbiota of two populations of primates that are seldom or never exposed to
      antibiotics: baboons and mangabeys. Most of these animals were part of a captive
      colony in Texas that is used for scientific studies of female physiology and
      physical anthropology topics. Samples from some wild baboons were also tested.
      Vaginal swab samples, obtained in connection with a study designed to define the
      normal microbiota of the female vaginal canal, were tested for the presence of
      two types of antibiotic resistance genes: tetracycline resistance (tet) genes and
      erythromycin resistance (erm) genes. These genes are frequently found in human
      isolates of the two types of bacteria that were a substantial part of the normal
      microbiota of primates (Firmicutes and Bacteroidetes). Since cultivation was not
      feasible, polymerase chain reaction and DNA sequencing were used to detect and
      characterize these resistance genes. The tet(M) and tet(W) genes were found most
      commonly, and the tet(Q) gene was found in over a third of the samples from
      baboons. The ermB and ermF genes were found only in a minority of the samples.
      The ermG gene was not found in any of the specimens tested. Polymerase chain
      reaction analysis showed that at least some tet(M) and tet(Q) genes were
      genetically linked to DNA from known conjugative transposons (CTns), Tn916 and
      CTnDOT. Our results raise questions about the extent to which extensive exposure
      to antibiotics is the only pressure necessary to maintain resistance genes in
      natural settings.

PMID- 19857139
TI  - CTX-M-2-producing Salmonella Typhimurium isolated from pediatric patients and
      poultry in Brazil.
AB  - Ten Salmonella enterica serovar Typhimurium isolates producing CTX-M-2 extended
      spectrum beta-lactamase were identified from clinical and poultry sources in two
      distant cities in Brazil between 2003 and 2004. They included two isolates from
      pediatric patients and eight isolates from poultry or its environment. All
      isolates exhibited coresistance to non-beta-lactam antimicrobials including
      tetracycline and trimethoprim/sulfamethoxazole. The CTX-M-2 gene was located on
      transferable plasmids with sizes between 90 and 170 kb that also carried other
      resistance determinants in some isolates. By pulsed-field gel electrophoresis,
      the genetic similarity of the isolates including clinical and poultry ones ranged
      from 89% to 100%.

PMID- 19857140
TI  - Occurrence and characteristics of class 1 and class 2 integrons in resistant
      Escherichia coli isolates from animals and farm workers in northeastern China.
AB  - The purpose of this study was to investigate the incidence of class 1 and class 2
      integrons and the presence of the gene cassettes in resistant Escherichia coli
      isolates from farm animals and farm workers in northeastern China during 2004
      2007. Most of E. coli isolates from farm worker and animal were multiresistant
      and showed a high resistance to aminoglycosides, chloramphenicol, amoxicillin,
      doxycyline, sulfanilamide, and quinolones. Integrons were found in 57.1% of the
      resistant E. coli isolates from animals and farm workers. Integrase genes were
      detected in 58.7% (101/172), 60.4% (64/106), and 26.1% (6/23) of resistant E.
      coli isolates from swine, chickens, and farm workers, respectively. Class 2
      integrons were detected only in resistant E. coli isolates from chickens and have
      one array cassette of dfrA1- sat1- aadA1- orfX. Dfr17- aadA5 was the most
      prevalent in resistant E. coli isolates from farm workers, swine, and chickens.
      Conjugative experiments demonstrated horizontal transfer of class 1 and class 2
      integrons between isolates of farm worker and animals. Our data revealed that
      multidrug resistance and class 1 integrons were widely present in E. coli
      isolates obtained in northeastern China. The horizontal transfer of integrons by
      conjugation seems to contribute to the wide dissemination of antimicrobial
      resistance in E. coli isolates of human and animal origins.

PMID- 19857141
TI  - Computational discovery of instructionless self-replicating structures in
      cellular automata.
AB  - Cellular automata models have historically been a major approach to studying the
      information-processing properties of self-replication. Here we explore the
      feasibility of adopting genetic programming so that, when it is given a fairly
      arbitrary initial cellular automata configuration, it will automatically generate
      a set of rules that make the given configuration replicate. We found that this
      approach works surprisingly effectively for structures as large as 50 components
      or more. The replication mechanisms discovered by genetic programming work quite
      differently than those of many past manually designed replicators: There is no
      identifiable instruction sequence or construction arm, the replicating structures
      generally translate and rotate as they reproduce, and they divide via a
      fissionlike process that involves highly parallel operations. This makes
      replication very fast, and one cannot identify which descendant is the parent and
      which is the child. The ability to automatically generate self-replicating
      structures in this fashion allowed us to examine the resulting replicators as
      their properties were systematically varied. Further, it proved possible to
      produce replicators that simultaneously deposited secondary structures while
      replicating, as in some past manually designed models. We conclude that genetic
      programming is a powerful tool for studying self-replication that might also be
      profitably used in contexts other than cellular spaces.

PMID- 19857142
TI  - Living technology: exploiting life's principles in technology.
AB  - The concept of living technology-that is, technology that is based on the
      powerful core features of life-is explained and illustrated with examples from
      artificial life software, reconfigurable and evolvable hardware, autonomously
      self-reproducing robots, chemical protocells, and hybrid electronic-chemical
      systems. We define primary (secondary) living technology according as key
      material components and core systems are not (are) derived from living organisms.
      Primary living technology is currently emerging, distinctive, and potentially
      powerful, motivating this review. We trace living technology's connections with
      artificial life (soft, hard, and wet), synthetic biology (top-down and bottom
      up), and the convergence of nano-, bio-, information, and cognitive (NBIC)
      technologies. We end with a brief look at the social and ethical questions
      generated by the prospect of living technology.

PMID- 19857143
TI  - Artificial symbiogenesis and differing reproduction rates.
AB  - Symbiosis is the phenomenon in which organisms of different species live together
      in close association. Symbiogenesis is the name given to the process by which
      symbiotic partners combine and unify. This letter reconsiders previous work using
      the NKCS model of coevolution to explore symbiogenesis. In particular, the role
      of different replication rates between the coevolving partners is considered.
      This is shown to provide a broader scope for the emergence of endosymbioses and
      subsequent horizontal gene transfers.

PMID- 19857144
TI  - Systems architecture: a new model for sustainability and the built environment
      using nanotechnology, biotechnology, information technology, and cognitive
      science with living technology.
AB  - This report details a workshop held at the Bartlett School of Architecture,
      University College London, to initiate interdisciplinary collaborations for the
      practice of systems architecture, which is a new model for the generation of
      sustainable architecture that combines the discipline of the study of the built
      environment with the scientific study of complexity, or systems science, and
      adopts the perspective of systems theory. Systems architecture offers new
      perspectives on the organization of the built environment that enable architects
      to consider architecture as a series of interconnected networks with embedded
      links into natural systems. The public workshop brought together architects and
      scientists working with the convergence of nanotechnology, biotechnology,
      information technology, and cognitive science and with living technology to
      investigate the possibility of a new generation of smart materials that are
      implied by this approach.

PMID- 19857145
TI  - The evolution of reaction-diffusion controllers for minimally cognitive agents.
AB  - This article describes work carried out to investigate whether a classic reaction
      diffusion (RD) system could be used to control a minimally cognitive animat. The
      RD system chosen was that first described by Gray and Scott, and the minimally
      cognitive behaviors were those used by Beer et al. involving the fixation and
      discrimination of diamond and circle shapes by a whiskered animat. A further task
      was added, which required the RD controllers to maintain and use a chemical
      memory. The parameters of these controllers were evolved using an evolutionary,
      or genetic, algorithm.

PMID- 19857146
TI  - Lack of effect on prematurity, birth weight, and infant growth from exposure to
      protease inhibitors in utero and after birth.
AB  - STUDY OBJECTIVE: To determine whether an association exists between exposure in
      utero and after birth to highly active antiretroviral therapy (HAART) containing
      protease inhibitors and prematurity, birth weight, and infant growth parameters.
      DESIGN: Retrospective cohort study. SETTING: Tertiary, university-affiliated
      hospital in Montreal, Canada. PATIENTS: Cohort of 206 pairs of mothers who had
      human immunodeficiency virus (HIV) and had been treated with HAART between 1997
      and 2005, of whom 176 had regimens containing protease inhibitors, and their
      infants, as well as a control group of 206 infants born to non-HIV-infected
      mothers and thus not exposed to HAART. MEASUREMENTS AND MAIN RESULTS: Demographic
      and clinical characteristics were retrieved from patients' medical records and
      the hospital's HIV database. Duration of HAART use, rates of prematurity and low
      birth weight, and infant growth parameters during the first 2 years of the
      child's life were evaluated. Median duration of HAART use for the women before
      delivery was 18 weeks (range 4-36 wks) and for infants, started within the first
      8-12 hours of life, was 6 weeks (range 2-6 wks). In infants exposed to HAART, the
      10.6% rate of prematurity (11.1% with and 7.1% without protease inhibitors) was
      not significantly higher than that in the control group (7.8%). Moreover, the
      9.9% rate for small for gestational age (9.8% with and 10.3% without protease
      inhibitors) was also not significantly higher than that in the control group
      (5.3%). The 176 mothers and infants exposed to protease inhibitors had a median
      follow-up of 5 years. Stillbirth or death was not observed. At delivery, the
      weight, length, and head circumference of the 176 infants exposed to protease
      inhibitors were similar to those of the control group. During the first 2 years
      of life, premature infants were in the lower percentiles of growth; however, they
      followed normal Centers for Disease Control and Prevention growth curves matched
      for age and sex. CONCLUSION: Significantly higher rates of prematurity and low
      birth weight were not demonstrated in infants exposed in utero to HAART with
      protease inhibitors. Moreover, these children reached normal growth percentiles
      during the first 2 years of life.

PMID- 19857147
TI  - Pharmacokinetic outcomes of a simplified, weight-based, extended-interval
      gentamicin dosing protocol in critically ill neonates.
AB  - STUDY OBJECTIVE: To determine the pharmacokinetic outcomes of a simplified,
      weight-based, extended-interval gentamicin dosing protocol for critically ill
      neonates. DESIGN: Retrospective medical record review with pharmacokinetic
      analysis. SETTING: Two neonatal intensive care units in a pediatric tertiary care
      system. PATIENTS: Sequential sample of 644 critically ill neonates less than 7
      days old without evidence of renal dysfunction who received gentamicin, dosed by
      using a simplified, weight-based, extended-interval dosing protocol, on the first
      day of life for suspected sepsis between February 2003 and January 2008, and who
      had subsequent gentamicin plasma concentrations measured during their first week
      of life. MEASUREMENTS AND MAIN RESULTS: Data were collected on birth weight,
      gestational age at birth, serum creatinine concentration during the first 10 days
      of life, medical conditions, and concomitant drugs. Gentamicin dosing and its
      pharmacokinetic parameters were noted for each patient. A mean dose of 3.96
      mg/kg/dose of gentamicin was administered intravenously every 48 hours in
      neonates weighing less than 1250 g at birth and every 24 hours in those weighing
      1250 g or more. If the neonate received concurrent indomethacin, however,
      gentamicin was given every 48 hours. Protocol success was defined as a peak
      gentamicin plasma concentration of 7-10 mg/L and a trough concentration less than
      2 mg/L. Mean gentamicin peak and trough concentrations were 9.38 mg/L (95%
      confidence interval [CI] 9.24-9.52 mg/L) and 1.00 mg/L (95% CI 0.96-1.04 mg/L),
      respectively. With use of the protocol, 361 neonates (56.1%) achieved gentamicin
      peak plasma concentrations in the range defined as successful and 610 neonates
      (94.7%) achieved successful trough concentrations. The mean gentamicin apparent
      volume of distribution and half-life were 0.48 L/kg (95% CI 0.47-0.49 L/kg) and
      8.31 hours (95% CI 8.09-8.52 hrs), respectively. CONCLUSION: This simplified,
      weight-based, extended-interval gentamicin dosing protocol for critically ill
      neonates was effective in achieving therapeutic peak plasma concentrations of
      gentamicin in most of the patients and, as a high proportion of patients had
      acceptable trough concentrations, may minimize the potential for toxicity.

PMID- 19857148
TI  - Primary antifungal prophylaxis in adult hematopoietic stem cell transplant
      recipients: current therapeutic concepts.
AB  - In recipients of hematopoietic stem cell transplants (HSCTs), the mortality
      associated with invasive fungal infections (IFIs) remains high, despite the
      introduction of broad-spectrum antifungal agents over the past 2 decades.
      Preventing exposure to fungal pathogens in this population is impossible;
      therefore, clinicians have focused on prophylactic use of antifungal agents to
      prevent IFIs in high-risk HSCT recipients. It is important to target antifungal
      prophylaxis by type of HSCT (autologous or allogeneic), local epidemiology, and
      risk factors for IFIs so that patients can receive the most appropriate agent
      while balancing costs and the risks of toxicity, and minimizing the development
      of resistance. To assist clinicians in weighing the pros and cons of currently
      available antifungal agents when choosing a suitable prophylactic regimen, we
      provide a review of several key prospective randomized trials that evaluated
      various antifungal agents for primary prophylaxis in adult HSCT recipients. In
      addition, we describe the epidemiology of and risk factors for IFIs in HSCT
      recipients, the difficulties in diagnosing IFIs, antifungal agents used for
      prophylaxis, and the goals of primary prophylaxis. Fluconazole remains the gold
      standard for primary prophylaxis in autologous HSCT recipients. For allogeneic
      HSCT recipients, the agent chosen for prophylaxis must be based on the patient's
      risk factors for IFIs. In low-risk patients, fluconazole is an appropriate agent
      to use for primary prophylaxis immediately after transplantation. However, in
      allogeneic HSCT recipients who develop complications, such as graft failure,
      graft-versus-host disease, or cytomegalovirus infection, prophylaxis with a mould
      active agent should be used.

PMID- 19857149
TI  - Antimicrobial susceptibility testing: a primer for clinicians.
AB  - Appropriate use of antimicrobials in health care continues to be a challenge.
      Reliable and reproducible antimicrobial susceptibility testing methods are
      necessary to provide the clinician with valuable information that can be
      translated into positive clinical outcomes at the bedside. However, there are
      nuances with these testing methods that, if unrecognized, could lead to
      misinterpretation of results and inappropriate antibiotic selection. This primer
      describes the common antimicrobial susceptibility tests used in the clinical
      microbiology laboratory and reviews how subtle differences in testing methods and
      technique can influence reported results. Clinicians who have a thorough
      understanding of qualitative and quantitative methods, automated susceptibility
      testing systems, and commonly used screening and confirmatory tests for
      antibiotic-resistant organisms can strengthen institutional antibiotic
      stewardship programs and improve patient outcomes.

PMID- 19857150
TI  - Management of venous thromboembolism and the potential to impact overall survival
      in patients with cancer.
AB  - The risk of venous thromboembolism (VTE) in patients with cancer is 6-12-fold
      higher than in the general population, and VTE is the second leading cause of
      death in this population, after cancer itself. The etiology underlying the
      increased risk of VTE is multifactorial and complex, involving patient-, tumor-,
      and treatment-related factors. In patients with cancer, cumulative results from
      studies in those with VTE versus without VTE suggest that anticoagulation
      therapy, particularly with low-molecular-weight heparins, prevents morbidity and
      may reduce mortality. Despite the availability of effective and safe therapeutic
      options, VTE is often underrecognized and suboptimally managed. Interventions
      such as assessing individual patient risk of VTE, providing VTE prophylaxis
      and/or prompt treatment, and adopting VTE guidelines are essential aspects of
      cancer-related care. Aggressive VTE management and strategies are critical to
      improving survival in patients with cancer and VTE.

PMID- 19857151
TI  - Use of antidepressants for management of hot flashes.
AB  - A growing body of evidence suggests that antidepressant therapies, particularly
      selective serotonin reuptake inhibitors and venlafaxine, are effective in the
      management of hot flash symptoms. Several of these agents have the support of the
      American College of Obstetricians and Gynecologists and the North American
      Menopause Society. To review the literature on antidepressants for the treatment
      of hot flashes in women, we searched the PubMed, International Pharmaceutical
      Abstracts, and MEDLINE databases from inception through May 2009. All publication
      types that included human participants and that were published in English were
      eligible for review. These articles, relevant abstracts, and additional
      references were used to collect pertinent data. Although initial small pilot
      trials were conducted solely in breast cancer survivors, additional studies have
      been conducted both in breast cancer survivors and in relatively healthy
      menopausal women. Data on the benefits with many of these agents are conflicting.
      Venlafaxine and paroxetine have been studied more extensively than any of the
      other antidepressants and are more consistent in effectively reducing the
      frequency and severity of hot flashes, based on these study results.
      Desvenlafaxine, sertraline, fluoxetine, and citalopram should be considered
      second- or third-line options if patients fail therapy with or cannot tolerate
      venlafaxine or paroxetine, based on the current published data. Duloxetine,
      escitalopram, fluvoxamine, and mirtazapine should be reserved as last-line
      therapy until more rigorous studies are conducted assessing their use in the
      management of hot flashes.

PMID- 19857152
TI  - Bendamustine: a new treatment option for chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a slow-growing hematologic malignancy and
      the most common type of leukemia in the western world. The lifetime risk for
      developing CLL is 1 in 216 men and women. Unfortunately, CLL is considered
      incurable with the chemotherapeutic agents available today. Bendamustine is a new
      agent that was recently added to the available regimens for the treatment of CLL.
      It was also recently approved for the treatment of non-Hodgkin's lymphoma. Its
      mechanism of action is unknown, but it contains an alkylating group similar to
      that of other bifunctional alkylating agents such as chlorambucil, and it also
      contains a benzimidazole central ring thought to exhibit antipurine-like
      properties. The United States Food and Drug Administration approved bendamustine
      based on results from an international phase III study of CLL in which
      bendamustine was compared with chlorambucil in treatment-naive patients. Ongoing
      clinical trials are assessing the utility of bendamustine in combination with
      other agents for the treatment of CLL, as well as for other malignancies.

PMID- 19857153
TI  - Key articles and guidelines in the treatment of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a significant medical diagnosis that affects
      millions of patients each year. Appropriate management of VTE can help treat the
      initial event as well as reduce the frequency of complications such as
      postthrombotic syndrome, pulmonary hypertension, and death. Due to increasing
      regulatory requirements, hospitals nationwide are developing necessary
      documentation of appropriate and safe use of anticoagulants for the management of
      VTE. It is essential that a wide range of clinicians have an understanding of
      what constitutes appropriate VTE treatment in various patient populations. With
      the existence of numerous pharmacologic agents, abundance of major clinical
      trials, and nationally recognized clinical guidelines, compiling the needed
      reference material to make evidence-based decisions on appropriate VTE treatment
      can be difficult for clinicians. Therefore we have provided bibliographies of key
      articles and guidelines related to the treatment of VTE with a number of
      different strategies in a variety of special patient populations. It is our hope
      that this compilation will serve as a resource for pharmacists, physicians,
      nurses, residents, and students responsible for the care of patients with VTE.

PMID- 19857154
TI  - Clinically significant adverse events from a drug interaction between quetiapine
      and atazanavir-ritonavir in two patients.
AB  - Clinicians caring for patients infected with the human immunodeficiency virus
      (HIV) and diagnosed with psychiatric comorbidities must be aware of potential
      drug-drug interactions, particularly with protease inhibitor-based antiretroviral
      therapy. Although possible interactions can be predicted based on a drug's
      pharmacokinetic parameters, the clinical significance is often unknown. We
      describe two patients who experienced serious quetiapine adverse effects
      potentially mediated through an interaction with ritonavir-boosted atazanavir.
      The first patient was a 57-year-old man with HIV and bipolar disease who
      developed rapid and severe weight gain when quetiapine was added to a stable
      atazanavir-ritonavir-based antiretroviral regimen. After the patient discontinued
      both quetiapine and ritonavir, his weight returned to its baseline value. The
      second patient was a 32-year-old woman with HIV, anxiety disorder, and a history
      of intravenous drug abuse who developed increased sedation and mental confusion
      when an atazanavir-ritonavir-based antiretroviral regimen was added to her stable
      antianxiety drug regimen, which included quetiapine. Her symptoms resolved
      promptly after discontinuation of the quetiapine. Use of the Naranjo adverse drug
      reaction probability scale indicated that the adverse effects experienced by the
      two patients were possibly related and probably related, respectively, to an
      interaction between quetiapine and atazanavir-ritonavir. Quetiapine is primarily
      metabolized by cytochrome P450 (CYP) 3A4, and ritonavir is a potent inhibitor of
      CYP3A4. Thus, it is reasonable to theorize that quetiapine concentrations will
      increase when these drugs are used concurrently, which would be the likely cause
      of the toxicities in these two patients. To our knowledge, these are the first
      published reports of a clinically significant interaction between atazanavir
      ritonavir and quetiapine. Clinicians should be aware of the potential for this
      interaction, and extreme caution should be used when prescribing quetiapine and
      other atypical antipsychotic agents in HIV-positive patients who are receiving
      antiretroviral therapy.

PMID- 19857155
TI  - Avoiding Guillan-Barre Syndrome following swine origin pandemic H1N1 2009
      influenza vaccination.

PMID- 19857158
TI  - The well-temperatured biologist. (American Society of Naturalists Presidential
      Address).
AB  - Temperature provides a powerful theme for exploring environmental adaptation at
      all levels of biological organization, from molecular kinetics to organismal
      fitness to global biogeography. First, the thermodynamic properties that underlie
      biochemical kinetics and protein stability determine the overall thermal
      sensitivity of rate processes. Consequently, a single quantitative framework can
      assess variation in thermal sensitivity of ectotherms in terms of single amino
      acid substitutions, quantitative genetics, and interspecific differences.
      Thermodynamic considerations predict that higher optimal temperatures will result
      in greater maximal fitness at the optimum, a pattern seen both in interspecific
      comparisons and in within-population genotypic variation. Second, the temperature
      size rule (increased developmental temperature causes decreased adult body size)
      is a common pattern of phenotypic plasticity in ectotherms. Mechanistic models
      can correctly predict the rule in some taxa, but lab and field studies show that
      rapid evolution can weaken or even break the rule. Third, phenotypic and
      evolutionary models for thermal sensitivity can be combined to explore potential
      fitness consequences of climate warming for terrestrial ectotherms. Recent
      analyses suggest that climate change will have greater negative fitness
      consequences for tropical than for temperate ectotherms, because many tropical
      species have relatively narrow thermal breadths and smaller thermal safety
      margins.

PMID- 19857159
TI  - Island species richness increases with habitat diversity.
AB  - Species richness is commonly thought to increase with habitat diversity. However,
      a recent theoretical model aiming to unify niche and island biogeography theories
      predicted a hump-shaped relationship between richness and habitat diversity.
      Given the contradiction between model results and previous knowledge, we examine
      whether the relationship between species richness and habitat diversity is
      consistently monotonically increasing and under which circumstances, if at all,
      such relationships could be hump shaped. We review the empirical evidence about
      the shape of such relationships and show that species richness on islands usually
      increases with habitat diversity and that it never decreases. We also critically
      examine the assumptions of the theoretical model and modify them to incorporate a
      less restrictive definition of niche width. The modified assumptions lead to
      simulations that better capture real patterns, using either simple parameters or
      observed distributions of niche breadth. Further work is needed to incorporate
      ecological interactions and metacommunity dynamics if the aim is to merge niche
      and island biogeography theories in a realistic modeling framework.

PMID- 19857160
TI  - Functional morphology of the gill in amazonian freshwater stingrays
      (chondrichthyes: potamotrygonidae): implications for adaptation to freshwater.
AB  - The gill morphologies of six species of potamotrygonid freshwater stingrays from
      the Amazon basin were investigated using light and electron microscopy. Some
      unique features were found in the potamotrygonid gill: (1) fingerlike
      protuberances on the gill filament, (2) an Alcian blue/periodic acid-Schiff
      positive histochemical reaction for several cell layers in the gill epithelium
      (except the basal ones), (3) pavement cells with numerous subapical mucous
      vesicles, (4) very large mucous cells, and (5) follicular Na(+)/K(+)-ATPase-rich
      (NKA-rich) mitochondria-rich cells (MRCs) in Potamotrygon sp. (known as the
      cururu ray). The fingerlike protuberances may constitute an additional resistance
      to water flow, helping to drive water through the lamellae. The secretion of a
      mucous substance by the pavement cells and mucous cells may help to protect the
      gills against mechanical injury and pathogens and aid in osmoregulation in the
      dilute water of the Amazon basin. All MRCs possess enfolded basolateral membranes
      and have poorly developed or absent tubular systems. NKA-rich MRCs are located
      high in the basolateral membrane. The cururu ray, which is endemic to the Rio
      Negro, has follicular NKA-rich MRCs (8-12 cells in cross section) that share the
      same apical pit in the filament; this may be considered to be an autapomorphy.
      The combination of these branchial characteristics may have favored tolerance to
      the freshwater environment during the evolution and diversification of
      potamotrygonids throughout the Amazon basin.

PMID- 19857161
TI  - Preparation of nasal temperature-sensitive in situ gel of Radix Bupleuri and
      evaluation of the febrile response mechanism.
AB  - OBJECTIVE: This study developed a nasal temperature-sensitive in situ gel system
      for Radix Bupleuri. METHOD: Using 20% Poloxamer 407 as the gel base and 6% PEG
      4000 adjusting the gelation temperature. RESULTS: The system is liquid at 4
      degrees C. It can change its phase to gel above 30 degrees C, which is close to
      the temperature in nasal cavity. The antipyretic effect produced by Radix
      Bupleuri in situ gel formulation was investigated in fevered rabbits. The results
      show that it can prolong the effective time to 24 hours compared with 4-6 hours
      in Radix Bupleuri intranasal solution. The antipyretic response mechanism was
      researched by evaluating the relationship between body temperature and
      concentrations of cyclic adenosine monophosphate in cerebrospinal fluid. The
      results showed that the two parameters were positively correlated (r = 0.9435, P
      < 0.05). Six hours later after given in situ gel, the concentrations of cAMP were
      significantly lower than those in the solution group. It confirmed that
      temperature-sensitive Radix Bupleuri in situ gel applied in the nasal sprays had
      a longer residence and release time. CONCLUSION: Radix Bupleuri nasal temperature
      sensitive in situ gel has a higher medical effect and a longer effective time.
      Compared to the traditional nasal spray, it is more applicable for the treatment
      of fever.

PMID- 19857162
TI  - T cell dynamics and the response to HAART in a cohort of HIV-1-infected elite
      suppressors.
AB  - Elite controllers or suppressors are untreated human immunodeficiency virus type
      1 (HIV-1)-infected patients who maintain undetectable viral loads. In this study,
      we show that most elite suppressors do not experience significant changes in T
      cell counts over a 10-year period. Interestingly, treatment of an elite
      suppressor with highly active antiretroviral therapy (HAART) led to a marked
      decrease in immune activation.

PMID- 19857164
TI  - Antimicrobial susceptibility testing: a review of general principles and
      contemporary practices.
AB  - An important task of the clinical microbiology laboratory is the performance of
      antimicrobial susceptibility testing of significant bacterial isolates. The goals
      of testing are to detect possible drug resistance in common pathogens and to
      assure susceptibility to drugs of choice for particular infections. The most
      widely used testing methods include broth microdilution or rapid automated
      instrument methods that use commercially marketed materials and devices. Manual
      methods that provide flexibility and possible cost savings include the disk
      diffusion and gradient diffusion methods. Each method has strengths and
      weaknesses, including organisms that may be accurately tested by the method. Some
      methods provide quantitative results (eg, minimum inhibitory concentration), and
      all provide qualitative assessments using the categories susceptible,
      intermediate, or resistant. In general, current testing methods provide accurate
      detection of common antimicrobial resistance mechanisms. However, newer or
      emerging mechanisms of resistance require constant vigilance regarding the
      ability of each test method to accurately detect resistance.

PMID- 19857163
TI  - Age-related susceptibility to infection with diarrheagenic Escherichia coli among
      infants from Periurban areas in Lima, Peru.
AB  - BACKGROUND: Diarrheagenic Escherichia coli strains are being recognized as
      important pediatric enteropathogens worldwide. However, it is unclear whether
      there are differences in age-related susceptibility to specific strains,
      especially among infants. METHODS: We conducted a passive surveillance cohort
      study of diarrhea that involved 1034 children aged 2-12 months in Lima, Peru.
      Control stool samples were collected from randomly selected children without
      diarrhea. All samples were analyzed for common enteric pathogens and for
      diarrheagenic E. coli with use of multiplex real-time polymerase chain reaction.
      RESULTS: The most frequently isolated pathogens in 1065 diarrheal episodes were
      diarrheagenic E. coli strains (31%), including enteroaggregative (15.1%) and
      enteropathogenic E. coli (7.6%). Diarrheagenic E. coli, Campylobacter species,
      and rotavirus were more frequently isolated from infants aged >or=6 months. Among
      older infants, diffusely adherent E. coli and enterotoxigenic E. coli were more
      frequently isolated from diarrheal samples than from control samples (P <.05).
      Children aged >or=6 months who were infected with enterotoxigenic E. coli had a
      4.56-fold increased risk of diarrhea (95% confidence interval, 1.20-17.28),
      compared with younger children. Persistent diarrhea was more common in infants
      aged <6 months (13.5% vs 3.6%; P <.001). Among children with diarrheagenic E.
      coli-positive samples, coinfections with other pathogens were more common in
      children with diarrhea than in control children (40.1% vs 15.6%; P <.001).
      CONCLUSIONS: Diarrheagenic E. coli strains were more frequently isolated in
      samples from older infants. In this setting with high frequency of pathogen
      exposure and high frequency of breastfeeding, we hypothesize that the major age
      related differences result from decreased exposure to milk-related protective
      factors and from increased exposure to contaminated food and water.

PMID- 19857167
TI  - Fever, shock, and pancytopenia in a patient treated with alemtuzumab.

PMID- 19857169
TI  - Use of post-natal antiretroviral prophylaxis for prevention of mother-to-child
      transmission of HIV is increasing in Italy.

PMID- 19857170
TI  - Treatment and CD4+ T cell count recovery among antiretroviral therapy-naive
      patients with HIV/AIDS.

PMID- 19857171
TI  - Why we need statistical inference.

PMID- 19857172
TI  - Ribavirin in crimean-congo hemorrhagic fever: primum non nocere.

PMID- 19857173
TI  - Subclinical infection with the novel Influenza A (H1N1) virus.

PMID- 19857178
TI  - 18 years of results with cemented primary hip prostheses in the Norwegian
      Arthroplasty Register: concerns about some newer implants.
AB  - BACKGROUND AND PURPOSE: Few studies have compared the long-term survival of
      cemented primary total hip arthroplasties (THAs), and several prostheses have
      been used without adequate knowledge of their endurance. We studied long-term
      outcome based on data in the Norwegian Arthroplasty Register. PATIENTS AND
      METHODS: The 10 most used prosthesis brands in 62,305 primary Palacos or Simplex
      cemented THAs reported to the Register from 1987 through 2007 were included.
      Survival analyses with revision as endpoint (for any cause or for aseptic
      loosening) were performed using Kaplan-Meier and multiple Cox regression with
      time-dependent covariates. Revision rate ratios (RRs) were estimated for the
      follow-up intervals: 0-5, 6-10, and > 10 years. RESULTS: 5 prosthesis brands
      (cup/stem combinations) (Charnley, Exeter, Titan, Spectron/ITH, Link IP/Lubinus
      SP; n = 24,728) were investigated with 0-20 year follow-up (inserted 1987-1997).
      After 18 years, 11% (95% CI: 10.6-12.1) were revised for any cause and 8.4% (7.7
      9.1) for aseptic loosening. Beyond 10 years of follow-up, the Charnley cup had a
      lower revision rate due to aseptic loosening than Exeter (RR = 1.8) and Spectron
      (RR = 2.4) cups. For stems, beyond 10 years we did not find statistically
      significant differences comparing Charnley with Titan, ITH, and SP stems, but the
      Exeter stem had better results (RR = 05). 10 prosthesis brands (9 cups in
      combination with 6 stems; n = 37,577) were investigated with 0-10 years of follow
      up (inserted from 1998 through 2007). The Charnley cup had a lower revision rate
      due to aseptic loosening than all cups except the IP. Beyond 5 years follow-up,
      the Reflection All-Poly cup had a 14 times higher revision rate. For stems,
      beyond 5 years the Spectron-EF (RR = 6.1) and Titan (RR = 5.5) stems had higher
      revision rates due to aseptic loosening than Charnley. The analyses also showed a
      marked improvement in Charnley results between the periods 1987-1997 and 1998
      2007. INTERPRETATION: We observed clinically important differences between
      cemented prosthesis brands and identified inferior results for previously largely
      undocumented prostheses, including the commonly used prosthesis combination
      Reflection All-Poly/ Spectron-EF. The results were, however, satisfactory
      according to international standards.

PMID- 19857179
TI  - Shoulder rhythm in patients with impingement and in controls: dynamic RSA during
      active and passive abduction.
AB  - BACKGROUND AND PURPOSE: Impingement syndrome is probably the most common cause of
      shoulder pain. Abnormal abduction and proximal humeral translation are associated
      with this condition. We evaluated whether the relative distribution between
      glenohumeral and scapular-trunk motions (the scapulohumeral rhythm) and the speed
      of motion of the arm differed between patients with impingement and a control
      group without shoulder symptoms. PATIENTS AND METHODS: 30 patients with shoulder
      impingement (Neer stage 2) and 11 controls were studied during active abduction
      and 21 patients and 9 controls were studied during passive abduction. Dynamic RSA
      at a speed of 2 simultaneous exposures per second was used to record the shoulder
      motions for 5-6 seconds. RESULTS: Within the interval statistically evaluated
      (observations between 20-55 degrees of relative active abduction in the
      glenohumeral joint), the patient group showed more scapular and trunk motions (p
      = 0.04), especially at up to 40 degrees. The pattern of motion at passive
      abduction was somewhat similar to that in the controls. Both controls and
      patients showed an increasing absolute (i.e. global) proximal displacement of the
      center of the humeral head with increasing active and passive abduction of the
      glenohumeral joint and humerus, without any certain difference between the
      groups. The mean maximum absolute proximal displacement in the patient and
      control groups amounted to about 30 mm and 20 mm, respectively. The corresponding
      relative displacement (with fixed scapula) was only 2.0 and 0.5 mm. Active
      abduction was initiated with angular velocity of about 50 and 80 degrees per
      second, respectively, in the patients and the controls. In both groups it
      decreased with progressing abduction down to about 20 degrees per second
      (controls) after 3 seconds without there being any statistically significant
      difference. The angular velocities at passive abduction showed a similar pattern,
      still without any difference. In both groups, the speed of proximal translation
      during active abduction peaked 0.5-1 second later than the speed of rotation and
      remained relatively even for about 1 second, followed by a deceleration.
      INTERPRETATION: We found that the glenohumeral-thoracoscapular ratio during
      abduction of the arm in our study, measured as the distribution of motion between
      the glenohumeral joint and the trunk in both controls and patients with
      impingement, was less than or equal to 1:1. This finding differs from earlier
      results, probably due to the use of a method with high resolution and small
      influence of motions out of the frontal plane. The reason for reduced
      glenohumeral motions in the early phase of active abduction in the patient group
      is uncertain, but pain or avoidance of pain elicited by the motion was probably
      of importance.

PMID- 19857180
TI  - Open reduction and internal fixation compared to closed reduction and external
      fixation in distal radial fractures: a randomized study of 50 patients.
AB  - BACKGROUND AND PURPOSE: In unstable distal radial fractures that are impossible
      to reduce or to maintain in reduced position, the treatment of choice is
      operation. The type of operation and the choice of implant, however, is a matter
      of discussion. Our aim was to investigate whether open reduction and internal
      fixation would produce a better result than traditional external fixation.
      METHODS: 50 patients with an unstable or comminute distal radius fracture were
      randomized to either closed reduction and bridging external fixation, or open
      reduction and internal fixation using the TriMed system. The primary outcome
      parameter was grip strength, but the patients were followed for 1 year with
      objective clinical assessment, subjective outcome using DASH, and radiographic
      examination. RESULTS: At 1 year postoperatively, grip strength was 90% (SD 16) of
      the uninjured side in the internal fixation group and 78% (17) in the external
      fixation group. Pronation/supination was 150 degrees (15) in the internal
      fixation group and 136 degrees (20) in the external fixation group at 1 year.
      There were no differences in DASH scores or in radiographic parameters. 5
      patients in the external fixation group were reoperated due to malunion, as
      compared to 1 in the internal fixation group. 7 other cases were classified as
      radiographic malunion: 5 in the external fixation group and 2 in the internal
      fixation group. INTERPRETATION: Internal fixation gave better grip strength and a
      better range of motion at 1 year, and tended to have less malunions than external
      fixation. No difference could be found regarding subjective outcome.

PMID- 19857181
TI  - The osteogenic response of undifferentiated human mesenchymal stem cells (hMSCs)
      to mechanical strain is inversely related to body mass index of the donor.
AB  - BACKGROUND: While the importance of physical factors in the maintenance and
      regeneration of bone tissue has been recognized for many years and the mechano
      sensitivity of bone cells is well established, there is increasing evidence that
      body fat constitutes an independent risk factor for complications in bone
      fracture healing and aseptic loosening of implants. Although mechanical causes
      have been widely suggested, we hypothesized that the osteogenic mechano-response
      of human mesenchymal stem cells (hMSCs) may be altered in obese patients.
      METHODS: We determined the phenotypic and genotypic response of undifferentiated
      hMSCs of 10 donors to cyclic tensile strain (CTS) under controlled in vitro
      conditions and analyzed the potential relationship relevant to the donor's
      anthropomorphometric and biochemical parameters related to donor's fat and bone
      metabolism. RESULTS AND INTERPRETATION: The osteogenic marker genes were all
      statistically significantly upregulated by CTS, which was accompanied by a
      significant increase in cell-based ALP activity. Linear correlation analysis
      revealed that there was a significant correlation between phenotypic CTS response
      and the body mass index of the donor (r = -0.91, p < 0.001) and phenotypic CTS
      response was also significantly related to leptin levels (r = -0.68) and
      estradiol levels (r = 0.67) within the bone marrow microenvironment of the donor.
      Such an upstream imprinting process mediated by factors tightly related to the
      donor's fat metabolism, which hampers the mechanosensitivity of hMSCs in obese
      patients, may be of pathogenetic relevance for the complications associated with
      obesity that are seen in orthopedic surgery.

PMID- 19857182
TI  - Growth rate after limb deformity correction by the Ilizarov method with or
      without knee joint distraction: lengthening in 30 children followed for at least
      2 years.
AB  - BACKGROUND AND PURPOSE: Growth inhibition and stimulation have both been reported
      after juvenile limb lengthening. Distraction of a joint usually suspends and
      unloads the growth plate and may stimulate growth. We investigated the influence
      of knee joint distraction on the speed of growth after limb lengthening. METHODS
      In a retrospective study, growth patterns were analyzed in 30 children mean 61
      (24-109) months after limb lengthening with the Ilizarov method, each child
      having more than 2 years of remaining growth. In 14 patients with knee joint
      instability, the knee was bridged over during lengthening for joint
      stabilization. Whether or not joint bridging and distraction would affect
      patterns of growth of the lengthened limb by unloading the growth plate was
      evaluated with a repeated measurements analysis of variance. RESULTS: After
      lengthening procedures, the proportionate leg-length discrepancy was found to
      decrease in 16 children, suggesting increased growth rate in the lengthened
      limbs. A statistically significantly faster growth rate was seen in 8 of 14
      patients with knee distraction as compared to patients with single bone frame
      configurations. INTERPRETATION: Further research is required to investigate
      whether growth stimulation is due to the surgical technique and whether joint
      distraction should be recommended during limb lengthening in growing children.

PMID- 19857184
TI  - Pancreatic cancer: gene therapy approaches and gene delivery systems.
AB  - IMPORTANCE OF THE FIELD: Due to the absence of early diagnosis, the highly
      invasive and metastatic features and the lack of effective therapeutic
      modalities, the prognosis of patients with pancreatic cancer is poor. Gene
      therapy is currently regarded as a potential and promising therapeutic modality
      for pancreatic cancer. AREAS COVERED IN THIS REVIEW: This article summarizes an
      update of gene therapy approaches and reviews the latest progress in gene
      delivery systems that have been tested on pancreatic cancer. WHAT THE READER WILL
      GAIN: The treatment effectiveness of gene combination therapy is better than that
      of the regulation of single-gene or single gene therapy approaches. Naked DNA is
      limited because of degradation by intracellular and extracellular nucleases.
      Virus vectors show high transfection efficiency but are limited due to
      immunogenicity, inflammatory response and potential carcinogenicity. Non-viral
      vectors, such as cationic polymers or inorganic nanoparticles, show an important
      feature that they can be easily modified, and the progress of materials science
      will provide more and better non-viral vectors, accordingly improving the
      efficiency and safety of gene therapy, which will make them the most promising
      vectors for pancreatic cancer.

PMID- 19857183
TI  - Surgery for scapula process fractures: good outcome in 26 patients.
AB  - BACKGROUND: Generally, scapula process fractures (coracoid and acromion) have
      been treated nonoperatively with favorable outcome, with the exception of widely
      displaced fractures. Very little has been published, however, regarding the
      operative management of such fractures and the literature that is available
      involves very few patients. Our hypothesis was that operative treatment of
      displaced acromion and coracoid fractures is a safe and effective treatment that
      yields favorable surgical results. METHODS: We reviewed 26 consecutive patients
      (27 fractures) treated between 1998 and 2007. Operative indications for these
      process fractures included either a painful nonunion, a concomitant ipsilateral
      operative scapula fracture, > or = 1 cm of displacement on X-ray, or a multiple
      disruption of the superior shoulder suspensory complex. All patients were
      followed until they were asymptomatic, displayed radiographic fracture union, and
      had recovered full motion with no pain. PATIENTS AND RESULTS: 21 males and 5
      females, mean age 36 (18-67) years, were included in the study. 18 patients had
      more than one indication for surgery. Of the 27 fractures, there were 13 acromion
      fractures and 14 coracoid fractures. 1 patient was treated for both a coracoid
      and an acromion fracture. Fracture patterns for the acromion included 6 acromion
      base fractures and 7 fractures distal to the base. Coracoid fracture patterns
      included 11 coracoid base fractures and 3 fractures distal to the base. Mean
      follow-up was 11 (2-42) months. All fractures united and all patients had
      recovered full motion with no pain at the time of final follow-up. 3 patients
      underwent removal of hardware due to irritation from hardware components that
      were too prominent. There were no other complications. INTERPRETATION: While most
      acromion and coracoid fractures can be treated nonoperatively with satisfactory
      results, operative management may be indicated for displaced fractures and double
      lesions of the superior shoulder suspensory complex.

PMID- 19857185
TI  - Therapeutic vaccines in metastatic castration-resistant prostate cancer:
      principles in clinical trial design.
AB  - Although docetaxel was approved for the treatment of metastatic castration
      resistant prostate cancer in 2004, additional therapies are still required.
      Prostate cancer is often slow-growing and expresses many tumor-associated
      antigens, making it a feasible target for immunotherapy. Several therapeutic
      cancer vaccines have been developed for prostate cancer, including antigen
      presenting-cell-based, vector-based, and whole tumor cell vaccines. Initial
      trials demonstrated that vaccine approaches have limited toxicity. Clinical
      trials of targeted biologic therapies have demonstrated that patient selection is
      vital, and there is preliminary evidence that clinical parameters can be used to
      encompass metastatic prostate cancer patients who will more probably respond to
      vaccine treatment. In addition to appropriate patient selection, a successful
      clinical trial must have an appropriate primary endpoint as well. Three
      randomized, 'placebo'-controlled studies in metastatic castration-resistant
      prostate cancer have suggested a clinically significant survival advantage in
      spite of a lack of improvement in time to progression, implying that overall
      survival is the ideal endpoint for such trials. Careful examination of data from
      completed immunotherapy clinical trials in prostate cancer has identified
      appropriate patient populations and endpoints. Those principles need to be
      applied to future trial design to properly evaluate prostate cancer vaccines.

PMID- 19857186
TI  - Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) Receptor-1 and
      Receptor-2 agonists for cancer therapy.
AB  - IMPORTANCE OF THE FIELD: Agents that activate the TNF-related apoptosis-inducing
      ligand death receptors, TRAIL-R1 and TRAIL-R2, have attracted substantial
      attention and investment as potential anti-cancer therapies. Preclinical studies
      of TRAIL-R agonists indicate that they may be efficacious in a wide range of
      tumor types, especially when combined with chemotherapeutic agents. AREAS COVERED
      IN THIS REVIEW: The rationale for clinical development of TRAIL-R agonists is
      described, including the basis for combining these agents with other agents that
      modulate the 'checks and balances' of the apoptotic pathways. Accruing data that
      highlight differences between TRAIL-R1 and TRAIL-R2 that could affect the
      clinical significance of their specific agonists are described. The clinical
      experience to date with each of the agonists is summarized. WHAT THE READER WILL
      GAIN: The reader will gain an understanding of the rationale for the clinical
      development of TRAIL-R agonists, as well as the current status of clinical trials
      of these interesting new agents. TAKE HOME MESSAGE: Ongoing clinical trials will
      provide important information regarding the future development of TRAIL-R
      agonists.

PMID- 19857187
TI  - Narrative-based intervention for word-finding difficulties: a case study.
AB  - BACKGROUND: Children with word-finding difficulties manifest a high frequency of
      word-finding characteristics in narrative, yet word-finding interventions have
      concentrated on single-word treatments and outcome measures. AIMS: This study
      measured the effectiveness of a narrative-based intervention in improving single
      word picture-naming and word-finding characteristics in narrative in a case
      study. METHODS & PROCEDURES: A case study, quasi-experimental design was
      employed. The participant was tested on picture naming and spoken word to picture
      matching on control and treatment words at pre-, mid-, and post-therapy and an 8
      month maintenance point. Narrative samples at pre- and post-therapy were analysed
      for word-finding characteristics and language production. A narrative-based
      language intervention for word-finding difficulties (NBLI-WF) was carried out for
      eight sessions, over 3 weeks. The data were subjected to a repeated-measures
      trend analysis for dichotomous data. OUTCOMES & RESULTS: Significant improvement
      occurred for naming accuracy of treatment, but not for control words. The pattern
      of word-finding characteristics in narrative changed, but the frequency did not
      reduce. CONCLUSIONS & IMPLICATIONS: NBLI-WF was effective in improving naming
      accuracy in this single case, but there were limitations to the research. Further
      research is required to assess the changes that may occur in language production
      and word-finding characteristics in narrative. Community clinicians are
      encouraged to refine clinical practice to ensure clinical research meets quality
      indicators.

PMID- 19857188
TI  - [The health problems which can brougth by 3G cell phones to our country].
AB  - At present, we are being exposed to electromagnetic pollution which is steadily
      increasing parallel to the technological advancements and which is invisible and
      unnoticeable in the short run. Electromagnetic waves which were previously used
      for therapeutic reasons have recently been uncontrollably used in daily life. By
      widespread use of 3rd generation (3G) cellular phones, the electromagnetic
      pollution has multiplied and brought us a huge amount of health dangers in our
      country. In this article, electromagnetic pollution, which is a comprehensive
      topic, and problems related with this kind of pollution which is rapidly
      increasing due to recent wide use of 3G cell phones are summarized in the light
      of the literature.

PMID- 19857189
TI  - Effect of injection of botulinum toxin on lateral pterygoid muscle used together
      with the arthroscopy in patients with anterior disk displacement of the
      temporomandibular joint.
AB  - OBJECTIVES: In this study, we aimed to study the effects of an additional lateral
      pterygoid muscle (LPM), botulinum toxin-A (BTX-A) injection on arthroscopic
      lysis, lavage and posterior band coagulations. Subjective and objective measures
      have been documented. PATIENTS AND METHODS: Fourty-three subjects (6 females, 37
      males; mean age 35 years; range 15 to 48 years) with 52 joints were enrolled in
      the study. Patients were divided into two groups. The first group was treated
      with arthroscopic lysis, lavage and posterior band coagulation. The second group
      received an injection of 20 U of BTX-A to the LPM in addition to the former
      treatment. Patients were assessed statistically in the 1st week, and in the 1st,
      3rd and 6th months postoperatively with the measures of lateral deviations,
      protrusions and visual analogue scale (VAS) values using Student-t test. RESULTS:
      Group 1 and group 2 showed significant results within themselves with the
      exception of the 3rd month values of right deviations in group 1. When groups
      were compared with each other; significant results were observed in left
      deviation values only in the 3rd month, protrusion in the 1st month, and most
      importantly VAS values starting from the 1st month. CONCLUSION: Botulinum toxin-A
      injection to the LPM mostly improved subjective measures starting from the 1st
      month. Other objective measures like protrusions, and deviations were not found
      to be affected generally. These findings suggest the improvement of symptoms with
      BTX-A injections in additon to the standard arthroscopy. However, diminishing
      effect of BTX-A and lack of information on the exact mechanism of action of toxin
      on temporomandibular joint necessitate further studies on this topic.

PMID- 19857190
TI  - [Function of outer hair cells in patients with pseudoexfoliation].
AB  - OBJECTIVES: In this study, we aimed to assess whether outer hair cell function in
      patients with pseudoexfoliation syndrome (PES) was affected or not. PATIENTS AND
      METHODS: Thirty-two patients (21 males, 11 females; mean age 69.8+/-9.3 years;
      range 49 to 86 years) with the diagnosis of PES and 23 healthy subjects (12
      males, 11 females; mean age 65.3+/-9.1 year; range 51 to 79 years) as control
      group were included in the study. All of the subjects were evaluated with pure
      tone audiometry, tympanometry, and transient otoacoustic emission tests. RESULTS:
      Sensorineural hearing loss was present in 28 patients with PES and in 13 healthy
      subjects (p<0.05). Transient otoacoustic emissions were present in 42 ears of
      patients with PES and in 32 ears of healthy subjects and there was no
      statistically significant difference between these two groups (p>0.05). Signal to
      noise ratios for PES and control groups were 5.1+/-4.4 dB and 5.2+/-4.2 dB,
      respectively (p>0.05). CONCLUSION: Our results confirmed the presence of
      sensorineural hearing loss in PES patients. However, we failed to show a
      difference in outer hair cell functions of this group. Further postmortem
      histopathologic studies are needed to delineate the causes of sensorineural
      hearing loss in patients with PES.

PMID- 19857191
TI  - [The efficacy of preoperative local bupivacain application on postoperative pain
      in patients who had undergone tonsillectomy].
AB  - OBJECTIVES: To investigate the efficacy of preoperative local bupivacain
      application on postoperative pain and complications in tonsillectomy. PATIENTS
      AND METHODS: Fourty-five patients (mean age 8.07+/-3.34 years; range 4 to 20
      years) who had undergone tonsillectomy were included in this study and they were
      divided into two groups. Study group included 30 patients and were preoperatively
      injected with 2.5 ml 0.5% bupivacain in each peritonsillar area. Control group
      included 15 patients and were injected with 0.9% NaCl. Both groups were compared
      with respect to operation and anesthesia duration, intraoperative blood loss and
      postoperative pain parameters (15. minute, 1, 4, 12, 16. and 24. hours). RESULTS:
      There were no statistically significant differences in operation or anesthesia
      duration and intraoperative bleeding between two groups (p>0.05). Postoperative
      pain at the 15th minute, and 1st hour, were significantly lower in controls when
      compared with study group (p<0.05). While these values were significant for the
      postoperative 15th minute, they were not significant for the 1st hour.
      Postoperative pain score at the 4th hour was significantly lower in the study
      group when compared with the control group (p<0.05). Postoperative pain score at
      the 24th hour was considerably lower in the study group when compared with the
      control group (p<0.01). CONCLUSION: Preoperative local bupivacain application
      reduces postoperative pain especially at the 24th hour in patients who have
      undergone tonsillectomy.

PMID- 19857192
TI  - [Our experience with surgery of non melanoma cutaneous malignancies of head and
      neck].
AB  - OBJECTIVES: To evaluate the cases underwent surgery with the diagnosis of head
      and neck non melanoma skin malignancies. PATIENTS AND METHODS: Clinical records
      of 89 patients (33 females, 56 males; mean age 65.4 years; ranges 41 to 87 years)
      who underwent excision and reconstruction with the diagnosis of skin malignancy
      at ENT clinics of Ege University Hospital between April 2004 and March 2006 and
      101 lesions were retrospectively reviewed. The patients who were diagnosed with
      non melanoma skin malignancy and whose surgical decisions were concluded at the
      common council of dermatology clinic, ear nose and throat clinic and oral
      diagnosis clinics were included in the study. In all cases pre- and postoperative
      pictures of lesions, pathological results and follow-up results were all
      evaluated. RESULTS: The 32 of 101 lesions were located at nasal esthetical unit
      and 15 of these were at alar region subunit. The second most common location was
      lip with 29 lesions and 24 of them were located at lower lip. The evaluation of
      flap techniques performed for the reconstruction of excision defect revealed that
      extending flap was the second common method with 12 cases after primary closure
      with 23 cases. The pathological results of these lesions were found to be
      squamous cell carcinomas with 49 lesions and basal cell carcinomas with 41
      lesions. In three cases the surgical margins were positive, meaning tumor still
      remains in normal tissue. Neck dissection was performed in seven patients. There
      was no patient with recurrent malignant lesion during the follow-up period
      mean=47.5 months (range 37-57 months). CONCLUSION: Cutaneous malignancies are the
      most common malignancy type worldwide. Successful results are available if these
      lesions are diagnosed early, excised with correct methods and reconstructed with
      appropriate techniques.

PMID- 19857193
TI  - [Stomal recurrence after total laryngectomy: clinical and patological analysis of
      risk factors].
AB  - OBJECTIVES: The aim of this study is to evaluate risk factors for stomal
      recurrence and to state and emphasize the importance of these factors. PATIENTS
      AND METHODS: This study was carried out retrospectively on 119 patients (116
      males, 3 females; mean age 56.8 years; range 31 to 86 years) with larynx cancer
      who underwent total laryngectomy. All patients were examined for T-stage and
      location of primary tumor, tracheotomy (preoperative or postoperative) opening
      time, modality of applied treatment, presence of pharyngeal stoma fistula and
      presence of cervical lymph node metastasis in the postoperative period. RESULTS:
      Five patients (4.2%) out of 119 had stomal recurrence. Development period of
      stomal recurrence after laryngectomy was found to be between six months and three
      years (mean: 16.6 months). CONCLUSION: The treatment of this fatal complication
      is very difficult, and it has a poor prognostic nature. As a result, presence of
      subglottic involvement and advanced tumors in our cases are considered as main
      risk factors.

PMID- 19857194
TI  - [Epidural abscess and encephalocele following tegmen defect due to mastoidectomy:
      a case report].
AB  - In chronic otitis media surgery, especially in cases with cholesteatoma,
      different complications can occur in the course of the operation or
      postoperatively. In our clinic, in one of the cases who had staged canal-wall
      down operation for otitis media with cholesteatoma, an iatrogenic 0.5x0.5 cm
      dural plate defect had occurred in tegmen tympani during the operation. In this
      article, we present an uncommon case who had encephalocele with epidural abscess
      because of unrepaired dural plate defect superimposed with early postoperative
      infection at the first month after the operation and we discuss it in the light
      of the literature.

PMID- 19857195
TI  - A very rare complication of acute sinusitis: subgaleal abscess.
AB  - A 12-year-old girl presented with a swollen right eye with three days of pain and
      a diffused swollen frontal region and head lasting for one day. On the computed
      tomography with contrast, diffused collection was detected in the subgaleal
      regions and subperiosteal of the right orbita. It was observed that she had
      bilateral maxillary, ethmoidal, and frontal sinusitis and an infected bilateral
      middle concha bullosa in the right side. No symptoms of intracranial complication
      and osteomyelitis in the frontal or other calvarial bones were determined. This
      case presentation is thought to be the first one in literature that is an acute
      sinusitis without an intracranial complication and osteomyelitis, but with a
      diffused subgaleal abscess resulting from a subperiosteal abscess.

PMID- 19857196
TI  - Hypercalcemia due to Graves' disease in a patient with thyroid hemiagenesis.
AB  - Thyroid hemiagenesis is a rare anomaly due to failure of development of one
      thyroid lobe during embryological life. A lot of thyroid disorders may accompany
      thyroid hemiagenesis. In this report, we present a case of thyroid hemiagenesis,
      who had moderate hypercalcemia due to Graves' disease. A 43-year-old woman
      presented with weight loss of more than 5 kg within one month, heat intolerance,
      and increased sweating. For the past month, she had been troubled by intermittent
      symptoms of vomiting, thirst, and constipation. On examination, she had
      tachycardia with no signs of dehydration. Pulse rate was 110 per minute. She had
      fine tremor, proximal muscle weakness, and asymmetric smooth goiter and
      hyperplasia in the right thyroid gland. Thyroid function tests confirmed the
      diagnosis of hyperthyroidism. Although hypercalcemia may be detected in patients
      with thyrotoxicosis, to the best of our knowledge, this is the first case report
      of thyroid hemiagenesis accompanying hypercalcemia due to thyrotoxicosis.

PMID- 19857197
TI  - Choanal polyp originating from the nasal septum: septochoanal polyp.
AB  - Most of the nasal polyps arise from the lateral walls of the nasal cavity. Nasal
      polyps originating from the nasal septum with choanal extension are extremely
      rare. We report a case of large choanal polyp that arised from the
      posterosuperior aspect of the nasal septum, and extended down to the oropharynx.
      A 52-year-old woman presented with a two-year history of progressive nasal
      obstruction and snoring. Findings of anterior rhinoscopy were in normal limits.
      We think that the term "septochoanal polyp" which, as far as we know, has not
      been mentioned in the literature before, can be used for this rare lesion.

PMID- 19857198
TI  - [Incidental pathologies found in neck dissection: an unusual case report].
AB  - During the pathologic examination of neck dissection specimens, unexpected
      findings within lymph nodes may occasionally be uncovered. Such findings may
      include the presence of a second primary tumor or inflammatory disease, the
      discovery of which may have implications on management and prognosis. Incidental
      papillary thyroid carcinoma and necrotizing granulomatous inflammation were found
      in addition to squamous cell carcinoma metastasis in the pathological study of
      the neck dissection specimen in a 70-year-old male patient with laryngeal
      squamous cell carcinoma. The diagnostic, therapeutic and prognostic features of
      this rare association were discussed in the light of the current literature.

PMID- 19857200
TI  - Future developments in osteoporosis therapy.
AB  - Anti-resorptives that prevent osteoclasts from resorbing bone are the mainstay of
      treatment for osteoporosis, while parathyroid hormone is the only agent available
      that stimulates osteoblasts to form bone. Advances in knowledge about metabolic
      pathways in bone cell biology have identified specific points of intervention
      whereby formation and function of osteoclasts and osteoblasts can be inhibited or
      stimulated. The next generation of therapies for osteoporosis may include
      molecules that antagonize integrin or inhibit Src tyrosine kinase, vacuolar H+
      ATPase, chloride channel or cathepsin K, thus preventing osteoclasts from
      attaching to bone, form a ruffled border, acidify resorption lacunae or digest
      organic bone matrix. At least some of these may form a novel class of anti
      resorptives capable of inhibiting bone resorption without being coupled to
      inhibition of bone formation. Human and mouse genetics studies demonstrating the
      pivotal role of the Wnt signaling pathway in bone metabolism have led to the
      development of strategies to disrupt Wnt signaling in order to increase bone
      formation. Selective androgen receptor modulators that produce an anabolic effect
      on muscle and bone without undesirable androgenic side effects can potentially be
      used to treat osteoporosis, aged-related frailty, muscle wasting disorders and
      glucocorticoid-induced osteoporosis. Studies involving these molecules are still
      in either preclinical or early investigational stage, without fracture data.
      Nonetheless, preliminary results hold the promise that at least some of these new
      therapies may develop into effective means of treating and preventing
      osteoporosis. Any new therapy for osteoporosis must take into consideration its
      safety, efficacy, affordability and specificity of action.

PMID- 19857201
TI  - The oxyanion hole of Pseudomonas fluorescens mannitol 2-dehydrogenase: a novel
      structural motif for electrostatic stabilization in alcohol dehydrogenase active
      sites.
AB  - The side chains of Asn191 and Asn300 constitute a characteristic structural motif
      of the active site of Pseudomonas fluorescens mannitol 2-dehydrogenase that lacks
      precedent in known alcohol dehydrogenases and resembles the canonical oxyanion
      binding pocket of serine proteases. We have used steady-state and transient
      kinetic studies of the effects of varied pH and deuterium isotopic substitutions
      in substrates and solvent on the enzymatic rates to delineate catalytic
      consequences resulting from individual and combined replacements of the two
      asparagine residues by alanine. The rate constants for the overall hydride
      transfer to and from C-2 of mannitol, which were estimated as approximately 5 x
      102 s-1 and approximately 1.5 x 103 s-1 in the wild-type enzyme respectively,
      were selectively slowed, between 540- and 2700-fold, in single-site mannitol 2
      dehydrogenase mutants. These effects were additive in the corresponding doubly
      mutated enzyme, suggesting independent functioning of the two asparagine residues
      in catalysis. Partial disruption of the oxyanion hole in single-site mutants
      caused an upshift, by >or=1.2 pH units, in the kinetic pK of the catalytic acid
      base Lys295 in the enzyme-NAD+-mannitol complex. The oxyanion hole of mannitol 2
      dehydrogenase is suggested to drive a precatalytic conformational equilibrium at
      the ternary complex level in which the reactive group of the substrate is
      'activated' for chemical conversion through its precise alignment with the
      unprotonated side chain of Lys295 (mannitol oxidation) and C=O bond polarization
      by the carboxamide moieties of Asn191 and Asn300 (fructose reduction). In the
      subsequent hydride transfer step, the two asparagine residues provide
      approximately 40 kJ/mol of electrostatic stabilization.

PMID- 19857202
TI  - The adaptor protein EBP50 is important for localization of the protein kinase A
      Ezrin complex in T-cells and the immunomodulating effect of cAMP.
AB  - We recently reported that the dual-specificity AKAP (A-kinaseanchoring protein)
      Ezrin targets type I PKA (protein kinase A) to the vicinity of the TCR (T-cell
      receptor) in T-cells and, together with PAG (phosphoprotein associated with
      glycosphingolipid-enriched membrane microdomains) and EBP50 [ERM
      (Ezrin/Radixin/Moesin)-binding phosphoprotein 50], forms a scaffold that
      positions PKA close to its substrate, Csk (C-terminal Src kinase). This complex
      is important for controlling the activation state of T-cells. Ezrin binds the
      adaptor protein EBP50, which again contacts PAG. In the present study, we show
      that Ezrin and EBP50 interact with high affinity (KD=58+/-7 nM). A peptide
      corresponding to the EB (Ezrin-binding) region in EBP50 (EBP50pep) was used to
      further characterize the binding kinetics and compete the Ezrin-EBP50 interaction
      by various methods in vitro. Importantly, loading T-cells with EBP50pep
      delocalized Ezrin, but not EBP50. Furthermore, disruption of this complex
      interfered with cAMP modulation of T-cell activation, which is seen as a reversal
      of cAMP-mediated inhibition of IL-2 (interleukin 2) production, demonstrating an
      important role of EBP50 in this complex. In summary, both the biochemical and
      functional data indicate that targeting the Ezrin-EBP interaction could be a
      novel and potent strategy for immunomodulation.

PMID- 19857199
TI  - Dendritic cells for active anti-cancer immunotherapy: targeting activation
      pathways through genetic modification.
AB  - Tumour immunotherapy has become a treatment modality for cancer, harnessing the
      immune system to recognize and eradicate tumour cells specifically. It is based
      on the expression of tumour associated antigens (TAA) by the tumour cells and
      aims at the induction of TAA-specific effector T cell responses, whilst
      overruling various mechanisms that can hamper the anti-tumour immune response,
      e.g. regulatory T cells (Treg). (Re-) activation of effector T cells requires the
      completion of a carefully orchestrated series of specific steps. Particularly
      important is the provision of TAA presentation and strong stimulatory signals,
      delivered by co-stimulatory surface molecules and cytokines. These can only be
      delivered by professional antigen-presenting cells, in particular dendritic cells
      (DC). Therefore, DC need to be loaded with TAA and appropriately activated. It is
      not surprising that an extensive part of DC research has focused on the delivery
      of both TAA and activation signals to DC, developing a one step approach to
      obtain potent stimulatory DC. The simultaneous delivery of TAA and activation
      signals is therefore the topic of this review, emphasizing the role of DC in
      mediating T cell activation and how we can manipulate DC for the pill-pose of
      enhancing tumour immunotherapy. As we gain a better understanding of the
      molecular and cellular mechanisms that mediate induction of TAA-specific T cells,
      rational approaches for the activation of T cell responses can be developed for
      the treatment of cancer.

PMID- 19857204
TI  - Role of lipid metabolism in hepatitis C virus assembly and entry.
AB  - HCV (hepatitis C virus) represents a major global health problem. A consistent
      body of evidence has been accumulating, suggesting a peculiar overlap between the
      HCV life cycle and lipid metabolism. This association becomes evident both for
      the clinical symptoms of HCV infection and the molecular mechanisms underlying
      the morphogenesis and entry process of this virus. The HCV core-lipid droplets
      association seems to be central to the HCV morphogenesis process. Moreover, the
      biogenesis pathway of very-low-density lipoproteins has been shown to be involved
      in HCV morphogenesis with MTP (microsomal triacylglycerol transfer protein), ApoB
      (apolipoprotein B) and ApoE (apolipoprotein E) as essential elements in the
      production of infectious HCV particles. HCV infectivity also correlates with the
      lipidation status of the particles. Furthermore, some HCV cellular receptors and
      the regulation of the entry process are also connected to lipoproteins and lipid
      metabolism. Specifically, lipoproteins modulate the entry process and the
      cholesterol transporter SR-BI (scavenger receptor class B type I) is a cellular
      entry factor for HCV. The present review aims to summarize the advances in our
      understanding of the HCV-lipid metabolism association, which may open new
      therapeutic avenues.

PMID- 19857203
TI  - Development of an intracellularly acting inhibitory peptide selective for PKN.
AB  - PKNs form a subfamily of the AGC serine/threonine protein kinases, and have a
      catalytic domain homologous with that of PKC (protein kinase C) in the C-terminal
      region and three characteristic ACC (antiparallel coiled-coil) domain repeats in
      the N-terminal region. The preferred peptide phosphorylation motif for PKNs
      determined by a combinatorial peptide library method was highly similar to that
      of PKCs within a 10-amino-acid stretch. Previously reported PKN inhibitory
      compounds also inhibit PKCs to a similar extent, and no PKN selective inhibitors
      have been commercially available. We have identified a 15-amino-acid peptide
      inhibitor of PKNs based on amino acids 485-499 of the C-terminal region of the C2
      like domain of PKN1. This peptide, designated as PRL, selectively inhibits the
      kinase activity of all isoforms of PKN (Ki=0.7 muM) towards a peptide substrate,
      as well as autophosphorylation activity of PKN in vitro, in contrast with PKC.
      Reversible conjugation by a disulfide bond of a carrier peptide bearing a
      penetration accelerating sequence to PRL, facilitated the cellular uptake of this
      peptide and significantly inhibited phosphorylation of tau by PKN1 at the PKN1
      specific phosphorylation site in vivo. This peptide may serve as a valuable tool
      for investigating PKN activation and PKN-mediated responses.

PMID- 19857206
TI  - Benzoyl peroxide and adapalene fixed combination: a novel agent for acne.

PMID- 19857207
TI  - British Association of Dermatologists' guidelines for biologic interventions for
      psoriasis 2009.

PMID- 19857208
TI  - In vitro model for penetration of sensory nerve fibres on a Matrigel basement
      membrane: implications for possible application to intractable pruritus.
AB  - BACKGROUND: Epidermal hyperinnervation occurs in dermatoses with intractable
      pruritus, such as atopic dermatitis, suggesting that the hyperinnervation is
      partly responsible for abnormal itch perception. OBJECTIVES: To investigate the
      mechanisms of penetration of sensory nerve fibres into the basement membrane of
      the skin. METHODS: A rat dorsal root ganglion neurone culture system consisting
      of Matrigel and a Boyden chamber containing a nerve growth factor (NGF)
      concentration gradient was used. In some experiments, matrix metalloproteinase
      (MMP) blockers and semaphorin 3A (Sema3A) were added to the culture system.
      Matrigel-coated membranes were stained with anti-Tau antibody, and the number of
      nerve fibres that crossed the membrane was counted. Expression of MMPs in the
      cultured neurones was examined at mRNA and protein levels by quantitative reverse
      transcription-polymerase chain reaction and immunocytochemistry, respectively.
      The activity was also examined by zymography. RESULTS: Nerve fibres penetrated
      into Matrigel in the presence of an NGF concentration gradient, which was dose
      dependently inhibited by GM6001, a broad-spectrum MMP inhibitor. Transcripts for
      MMP2, but not MMP9, were increased in the cultured neurones, and the penetration
      was dose-dependently inhibited by MMP-2 blockers. MMP-2 and its activity were
      partially localized on the NGF-responsive growth cones. NGF also upregulated pro
      MMP-2 activation molecules in the cultured neurones. Sema3A stimulation showed
      the opposite effects on these NGF-dependent events. Interestingly, MMP2
      expression was modulated by extracellular matrix (ECM) substrates for this
      enzyme. CONCLUSIONS: Membrane-associated MMP-2 contributes to penetration of
      nerve fibres into Matrigel through modulation by axonal guidance molecules and/or
      ECM. These findings provide insight for understanding the development of
      intractable pruritus involving epidermal nerve density.

PMID- 19857209
TI  - Natural moisturizing factor components in the stratum corneum as biomarkers of
      filaggrin genotype: evaluation of minimally invasive methods.
AB  - BACKGROUND: The carriers of loss-of-function mutations in the filaggrin gene
      (FLG) have reduced levels of natural moisturizing factor (NMF) in the stratum
      corneum. The concentration of NMF components which are formed by filaggrin
      protein breakdown in the stratum corneum might therefore be useful as a biomarker
      of the FLG genotype. OBJECTIVES To investigate the feasibility of different
      sampling methods for the determination of two NMF components, 2-pyrrolidone-5
      carboxylic acid (PCA) and urocanic acid (UCA), in the stratum corneum as
      biomarkers for the FLG genotype. METHODS: PCA and UCA from the stratum corneum
      were sampled by using a tape stripping technique and an extraction technique
      using skin patches containing potassium hydroxide (KOH). The concentrations of
      PCA and UCA were measured by high-performance liquid chromatography. Eleven
      carriers of an FLG mutation and 10 individuals wild type for the two most common
      FLG mutations (R501X and R2447X) [corrected] were included in the study. RESULTS:
      The most significant difference between the FLG genotypes was found for PCA
      sampled by the tape stripping technique. The mean values of PCA obtained by the
      tape stripping technique were, respectively, 0.18, 0.50 and 1.64 mmol g(-1)
      protein in homozygous (or compound heterozygous), heterozygous and wild-type
      genotypes (P < 0.005 homozygous vs. heterozygous; P < 0.0001 heterozygous vs.
      wild type). The tape stripping technique showed less intrasubject variation
      compared with the KOH patches, in particular when the concentrations of UCA and
      PCA on the tape strips were normalized for protein amount. CONCLUSIONS: The
      concentration of PCA in the stratum corneum collected by tape stripping showed it
      to be a feasible biomarker of the FLG genotype.

PMID- 19857210
TI  - Contact allergy to allergens of the TRUE-test (panels 1 and 2) has decreased
      modestly in the general population.
AB  - BACKGROUND: The prevalence of contact allergy in the general population is nearly
      20%. OBJECTIVES: This study aimed to monitor the development of contact allergy
      to allergens from the TRUE-test (panels 1 and 2) between 1990 and 2006. METHODS:
      Two random samples of adults from the general population in Copenhagen, Denmark,
      were invited to participate in a general health examination including patch
      testing. In 1990 and 2006, we patch tested and questioned 543 and 3460 adult
      Danes. Patch test readings were performed on day 2 only. RESULTS: The overall
      prevalence decreased significantly from 15.5% in 1990 to 10.0% in 2006, mainly as
      a result of a decrease in thimerosal allergy from 3.4% to 0.8%. Furthermore, the
      prevalence of cobalt allergy and rubber-related allergens decreased from 1.1% to
      0.2% and from 1.5% to 0.2%, respectively. Stratification by sex and age group
      revealed decreasing prevalences of contact allergy in all male age groups and in
      young and middle-aged female age groups (18-55 years) whereas increasing
      prevalences were observed among older women (56-69 years). The diverging trend
      observed in women was probably explained by a cohort effect due to a change in
      the prevalence of nickel allergy following the Danish regulation on nickel
      exposure. CONCLUSIONS: Although the overall prevalence of contact allergy
      decreased in the general population, frequent contact allergens such as fragrance
      mix II and methyldibromo glutaronitrile were not tested. Thus, contact allergy
      remains prevalent in the general population.

PMID- 19857211
TI  - Measuring patient-relevant benefits in pruritus treatment: development and
      validation of a specific outcomes tool.
AB  - BACKGROUND: The assessment of patient-relevant benefit is gaining importance in
      evaluating treatments. The 'Patient Benefit Index, standard version'
      questionnaire (PBI-S) is a validated instrument to assess patients' treatment
      needs and benefits in skin diseases. Before therapy, the patient rates the
      importance of predefined treatment goals; after therapy, he rates the extent to
      which these goals have been achieved. Thus far, no such instrument has been
      developed specifically for pruritus. OBJECTIVES: Development and validation of a
      patient-relevant benefit questionnaire in the treatment of pruritus. METHODS:
      Fifty patients with pruritus were questioned on impairments due to pruritus and
      treatment needs. Four treatment objectives not already covered by the PBI-S were
      added to obtain a disease-specific instrument. This was tested for feasibility by
      36 patients with pruritus and validated in a sample of 100 patients with
      pruritus. RESULTS: The instrument was feasible in clinical practice. There were <
      2% missing values. Cronbach's alpha of the needs questionnaire was 0.93.
      Convergent validity was demonstrated with respect to reduction of pruritus and
      quality of life. CONCLUSIONS: The PBI for pruritus is a feasible, reliable and
      valid instrument that is highly accepted in daily routine for recording patient
      reported benefit.

PMID- 19857213
TI  - Genus-level supertree of Cyprinidae (Actinopterygii: Cypriniformes), partitioned
      qualitative clade support and test of macro-evolutionary scenarios.
AB  - We used the supertree approach of matrix representation with parsimony to
      reconstruct to date the most exhaustive (genus-level) phylogeny of Cyprinidae.
      The supertree of Cyprinidae, representing 397 taxa (237 nominal genera) and 990
      pseudocharacters, was well resolved (96%) through extended consensus majority
      rule, although 36 nodes (9.4%) were unsupported. The proportion of shared taxa
      among source trees was very low after calculation of the taxonomic coverage index
      (TCI = 0.059), which is proposed here as a more accurate alternative to the usual
      ratios calculated from the number of pseudo-characters or source trees per taxon.
      We define a new index for the calculation of partitioned qualitative clade
      support, the partitioned rQS ((p)rQS), which offers a straightforward
      visualization of the relative supports of source tree partitions at supertree
      nodes.The use of (p)rQS showed that the molecular source tree partition
      contributed to most node supports within the supertree of Cyprinidae (73%, contra
      21% for the morphological partition) and evidenced a fair proportion of conflict
      at nodes between the two partitions (21%), notably reflecting (i) the greater
      number and resolution of molecular source trees, and (ii) potential morphological
      convergences. Most of the higher-level relationships within Cyprinidae were
      supported by both morphological and molecular source tree partitions. Our
      supertree showed a well-supported dichotomy between a clade consisting of a
      'barbine' + 'rasborine' lineage, sister group to (Barbinae [paraphyletic],
      (Cyprininae, Labeoninae)), and a clade consisting of other rasborines (large
      polytomy) and the two monophyletic groups ((Tincinae, Tanichthys), (Ecocarpia,
      (Acheilognathinae, (Gobioninae, Leuciscinae)))) and (Squaliobarbinae,
      (Xenocyprinae, Cultrinae)). Through the non-monophyly of almost all the
      traditional subfamilies of Cyprinidae and 34 genera, our supertree exemplified
      the taxonomic chaos that reigns in the classification of the family. It also
      highlighted that further efforts should aim at increasing taxonomic sampling and
      generating alternative phylogenetic signals, notably for the still poorly
      apprehended Tincinae, Squaliobarbinae, Acheilognathinae, Gobioninae, and
      Rasborinae, the latter representing a key taxon for the understanding of early
      cyprinid evolution. Our supertree also proved useful for testing macro
      evolutionary scenarios at a wide taxonomic scale. Ancestral reconstructions using
      linear parsimony confirmed that the Oriental tropical region was the centre of
      origin of Cyprinidae, and identified three Oriental-to-Palaearctic, two
      Palaearctic-to-Nearctic, and one Oriental-to-Afrotropical major migration events.
      On the other hand, we almost completely rejected the hypothesis of presence of
      barbels as a plesiomorphic condition within Cyprinidae (although ambiguous for
      maxillary barbels of the Barbinae-Cyprininae type). The supertree of Cyprinidae
      serves as a basis to discuss the applications and bias of the newly proposed
      (p)rQS, to provide future guidelines for a better achievement of cyprinid
      phylogeny, and to elaborate further on inter-continental migrations and the
      adaptive value of barbels.

PMID- 19857214
TI  - Generalized anxiety disorder and irritable bowel syndrome.

PMID- 19857216
TI  - Definition of hospital-acquired pneumonia and characteristics of guidelines in
      Japan.
AB  - Hospital-acquired pneumonia is defined as pneumonia that appears for the first
      time within 48 h of hospital admission. Special care is needed in treatment
      because of poor patient conditions, including the underlying disorder,
      immunocompetence and general status. The 2002 hospital-acquired pneumonia
      guidelines were reviewed, and the current revisions were made based on those
      findings with the aim of producing simple and practical guidelines. Differences
      are seen between hospital-acquired pneumonia in the USA and Japan, and hospital
      acquired pneumonia treatment guidelines matched to circumstances in Japan were
      considered necessary.

PMID- 19857217
TI  - Diagnosis of hospital-acquired pneumonia and methods of testing for pathogens.
AB  - Hospital-acquired pneumonia is diagnosed in patients who, in addition to abnormal
      shadowing on chest radiography, have >or=2 of the following: fever, abnormal
      white blood cell count and purulent discharge. Treatment effect is judged from
      clinical symptoms and microorganism test results 2-3 days after the start of
      treatment, and reassessment is made with regard to change, addition or
      discontinuation of antimicrobial agents. Coordination with the microbiology
      laboratory is extremely important in diagnosing infectious diseases.
      Microorganisms isolated from tracheal aspirate at 10(6) cfu/mL (3+), from BAL at
      10(4)-10(5) cfu/mL (2+) and from a protected specimen brush at 10(3) cfu/mL (1+)
      have a high possibility of being the causative microorganisms. Pneumonia can
      almost be ruled out when no significant microbes are detected from the lower
      respiratory tract in patients with suspected ventilator-assisted pneumonia (when
      no change has been made to antimicrobial administration within 72 h). When MRSA
      or Pseudomonas aeruginosa are not detected in sputum tests, involvement of these
      drug-resistant bacteria may be considered unlikely, and the case treated
      accordingly. Involvement of aspiration is suspected when a number of pathogens
      are observed in lower respiratory tract specimens. When antimicrobials are
      administered with reference to breakpoint concentrations in Western countries,
      differences in dosage between these countries and Japan need to be considered.

PMID- 19857218
TI  - Basic approach for the selection of antibacterial agents.
AB  - In these guidelines, antimicrobials are selected according to the severity
      ranking and in conformance with the health insurance system in Japan and the
      prevailing situation with regard to hospital-acquired pneumonia. Reference was
      made to the 2005 ATS/IDSA guidelines as precedents for guidelines regarding
      hospital-acquired pneumonia. After examining these guidelines, the need to
      consider the medical system and particularities of infectious disease treatment
      in each country was identified. Preparation of these guidelines was thus
      necessary to take into consideration special conditions in Japan, including the
      long period of hospitalization, large number of patients with mild pneumonia, and
      large differences in test methods and antimicrobial doses. In the selection of
      specific antimicrobials, the mild group (A) corresponds to the early-onset group
      or the group with no risk factors for drug-resistant strains of bacteria in the
      ATS/IDSA guidelines, and the severe group (C) corresponds to the late group or
      group with risk of drug-resistant bacteria. Antimicrobial selection for the
      moderate group (B) between these two groups is carried out with consideration of
      drug-resistant bacteria, including Pseudomonas aeruginosa. In cases when MRSA is
      suspected, administration of anti-MRSA agents is recommended in addition to the
      antimicrobial for the respective group. Moreover, according to
      pharmacokinetic/pharmacodynamic theory, a sufficient antimicrobial dose needs to
      be administered in the early stage. As the efficacy of aminoglycoside drugs may
      be low using the doses and administration methods applied in Japan,
      administration using therapeutic drug monitoring is emphasized.

PMID- 19857219
TI  - Determining treatment effectiveness and period of treatment.
AB  - Judging the effect of treatment for hospital-acquired pneumonia is difficult
      using only inflammatory parameters or findings from chest radiography.
      Preferably, treatment effects should be judged comprehensively from body
      temperature, findings of chest radiography, inflammatory parameters, status of
      purulent discharge, bacteriological findings and oxygenation. In VAP, the
      parameter most closely correlated with prognosis is trend in PaO(2)/FiO(2).
      Clinical improvements are normally seen within 72 h. Antimicrobials thus should
      not be changed until the third day unless a dramatic deterioration in symptoms is
      seen. With the exception of pneumonia from microbes that tend to possess strong
      resistance, such as Pseudomonas aeruginosa, a treatment period of 7-10 days is
      adequate if the early-stage drugs are effective. If no improvements in the course
      are achieved by 3 days after starting treatment, an investigation should be made
      into whether treatment should be continued or changed to a different
      antimicrobial agent.

PMID- 19857220
TI  - Establishment of new severity ratings based on analysis of hospital-acquired
      pneumonia.
AB  - The Japanese Respiratory Society issued its first guidelines for the management
      of hospital-acquired pneumonia in adults in 2002. Pathological and severity
      ratings were investigated based on the results of a national multicenter survey
      of hospital-acquired pneumonia, and the new severity ratings shown below were
      established (Fig. II-1). Severity ratings in the 2002 guidelines were based
      mainly on markers that predicted the effectiveness of antimicrobial treatment. In
      the current revision, severity is rated using markers that predict the prognosis
      of patients. Five criteria were established as factors that predict prognosis:
      malignant tumour or immunocompromised status; decreased level of consciousness;
      FiO(2) >35% required to maintain SpO(2) >90%; age >or=70 years in men or >or=75
      years in women; and oliguria or dehydration. Two criteria were established as
      factors specifying the severity of the pneumonia itself: CRP >or=200 mg/L and
      shadows infiltrating more than two-thirds the area of one lung on chest
      radiography. Patients who satisfy up to two of the five criteria above to predict
      prognosis are classified in the mild group (Group A) if they do not satisfy
      either of the two criteria specifying severity of pneumonia, or in the moderate
      group (Group B) if they satisfy one or both of those two criteria. Patients who
      satisfy three or fewer of the five criteria to predict prognosis are classified
      in the severe group (Group C). When the new severity ratings were applied to the
      results of the national multicenter survey of hospital-acquired pneumonia, the
      mortality rate was found to be 12.1% (101/834) in the mild group (Group A), 24.9%
      (69/277) in the moderate group (Group B) and 40.8% (98/240) in the severe group
      (Group C). Statistically-significant differences were seen between groups, and
      patient classification may be useful as an indicator of prognosis (Fig. II-2).

PMID- 19857221
TI  - Strategies for non-responders.
AB  - When improvements in symptoms of hospital-acquired pneumonia are difficult to
      see, an investigation should be made into whether there truly is no response to
      antimicrobial treatment. Non-infectious disease that results in pneumonia-like
      shadows needs to be excluded. In pneumonia that is unresponsive to
      antimicrobials, differential diagnoses must be made with consideration of
      causative microorganism factors, host factors and medication factors,
      respectively. Preferably, the dose, administration frequency and administration
      time for the administered antimicrobials should be established based on PK/PD.

PMID- 19857222
TI  - Pneumonia in immunocompromised patients.
AB  - The diagnosis and identification of causative microorganisms of pneumonia are
      often difficult in immunocompromised patients. Immunosuppression can divided into
      three categories; neutropenia (or neutrophil dysfunction); humoral
      immunodeficiency and cellular immunodeficiency. Presumptive pathogen
      identifications of pneumonia could be made systematically based on the type of
      impaired immune function. Since there are a number of diseases that must be
      differentiated, the collection of respiratory tract specimens and appropriate
      serum antigen tests should be done whenever possible to identify the causative
      microorganisms. Empirical antibiotic therapy should be started as soon as
      possible. If initial treatment proves ineffective, invasive diagnostic
      procedures, including surgical lung biopsy, should be considered.

PMID- 19857223
TI  - Ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia is a pneumonia that develops initially more than
      48 h from the start of tracheal intubation and mechanical ventilation. The route
      of infection is almost always through the respiratory tract. Intake of
      contaminants from outside the tracheal tube (silent aspiration) is considered a
      key route, and suctioning of secretions that have accumulated above the cuff of
      the endotracheal tubes is effective in preventing infection. The circuit is
      managed and heated-wire humidifiers and suction are manipulated based on
      appropriate infection control measures. To diagnose pathogens, efforts should be
      made to collect specimens from the pneumonia focus. Realistically, however,
      diagnosis can also be achieved based on the clinical course and from the results
      of culture of samples from tracheal aspirate. Use of prophylactic antimicrobials
      is not recommended, but once a diagnosis is made, antimicrobials are administered
      that combat the causative microorganism.

PMID- 19857224
TI  - Aspiration pneumonia.
AB  - Aspiration pneumonia is diagnosed upon confirmation of inflammatory findings in
      the lungs and overt aspiration (apparent aspiration) or a condition in which
      aspiration is strongly suspected (abnormal swallowing function and dysphagia). In
      hospital-acquired pneumonia, this occurs as one consequence of frequent silent
      aspiration. In the diagnosis of aspiration pneumonia, evaluation of the risk of
      silent aspiration during the night and evaluation of swallowing function are
      important. The causative microorganisms in aspiration pneumonia, similar to
      community-acquired pneumonia, are basically thought to be bacteria residing in
      the oral cavity, such as pneumococcus, Haemophilus influenzae, Staphylococcus
      aureus and anaerobes. Hospital-acquired aspiration pneumonia often occurs with no
      distinction between apparent and silent aspiration, and in many cases, aspiration
      of foreign substances is serious when dysphagia itself is severe. In the
      treatment of aspiration pneumonia, use of antimicrobials for the pneumonia itself
      and early measures to prevent aspiration are important.

PMID- 19857225
TI  - Adjuvant therapy with steroids or immunoglobulins.
AB  - Chemotherapy with antimicrobials is the basic treatment for pneumonia. Compared
      with community-acquired pneumonia, more cases of hospital-acquired pneumonia
      develop serious complications with ALI/ARDS, disseminated intravascular
      coagulation (DIC) or other conditions, and in many cases a number of drugs are
      used as adjuvant therapies. Adjuvant therapies include steroids, immunoglobulins,
      granulocyte-colony stimulating (G-CSF), blood purification and neutrophil
      elastase inhibitors. Little evidence has been accumulated in favour of these
      adjuvant therapies in pneumonia and their use is left to the discretion of the
      physician, but the indications should be considered carefully and general use
      avoided.

PMID- 19857226
TI  - Use of antimicrobials in aged people and patients with decreased renal function.
AB  - Respiratory infections develop easily in aged people and are often difficult to
      treat. Renal function is poorer in aged people than in healthy adults, and the
      half-life of antimicrobials in blood is longer. General weight loss is present in
      many cases, and care needs to be taken in determining dosage. A high possibility
      exists for hospital-acquired pneumonia to become serious, particularly in aged
      people, and appropriate antimicrobials should be selected. Body weight and renal
      function must be considered when setting dosages, and use of 50-70% of the amount
      used in healthy adults is common. Side-effects are no different to those in
      healthy adults, but care is needed due to insufficient reserve capacity in aged
      people and a tendency for diseases to become serious due to the reluctance of
      aged patients to complain.

PMID- 19857227
TI  - Expanding the toolbox for phylogeographic analysis.

PMID- 19857228
TI  - Rhodopsin population genetics and local adaptation: variable dim-light vision in
      sand gobies is illuminated.
AB  - The visual pigments of fish are thought to be adapted to the variable spectral
      qualities of aquatic light environments. Most research on the role of natural
      selection on the evolution of rhodopsins and dim-light vision in fish has focused
      on variation among species and higher taxa. In this issue, Larmuseau et al.
      reveal substantial intraspecific sequence variation in RH1 (the rhodopsin gene)
      in sand gobies (Pomatoschistus minutus). Using population genetics and molecular
      evolution approaches, they detect positive selection on RH1 and find evidence for
      adaptation to local light conditions.

PMID- 19857230
TI  - Scientific and clinical: In this issue - November 2009.

PMID- 19857231
TI  - Re: Trick or treatment.

PMID- 19857232
TI  - Re: Trick or treatment.

PMID- 19857233
TI  - Detection of Minchinia occulta in samples of pearl oysters Pinctada maxima
      infected by Haplosporidium hinei.
AB  - OBJECTIVE: To determine if juvenile pearl oysters (Pinctada maxima) infected with
      Haplosporidium hinei are also infected with another haplosporidian parasite,
      Minchinia occulta. DESIGN: Archived samples of pearl oysters infected with H.
      hinei were examined using polymerase chain reaction (PCR) assays and in situ
      hybridisation (ISH) to analyse and identify haplosporidians. A 144-bp and 220-bp
      region of Minchinia DNA were targeted by PCR and amplified DNA from formalin
      fixed H. hinei-infected pearl oyster samples was sequenced. A 25-bp
      oligonucleotide probe targeting a variable section of the parasite's small
      subunit rRNA gene was used in ISH. RESULTS: The results of DNA-based diagnostic
      assays supported each other. The sequences obtained by PCR were found to be
      almost identical to M. occulta from rock oysters and the ISH assay demonstrated
      infection with M. occulta in affected pearl oysters. ISH indicated a prevalence
      of infection of 26.7% in one of the previous outbreaks. CONCLUSION: Pearl oyster
      spat are susceptible to infection by a Minchinia parasite, most likely M.
      occulta, which was recently identified in rock oysters within the pearl-producing
      zones of Western Australia and is associated with mortalities of up to 80% in
      this species. The occurrence of haplosporidian co-infections in pearl oysters
      suggests the immunocompetence of juvenile oysters may be an important factor in
      preventing infection and therefore preventing mortalities such as those occurring
      in the recent outbreaks of pearl oyster oedema disease.

PMID- 19857235
TI  - Tibial wedge ostectomy: complications of 300 surgical procedures.
AB  - BACKGROUND: Tibial wedge ostectomy (TWO) is a surgical procedure that aims to
      give functional stability during weight-bearing in a hindlimb with cranial
      cruciate ligament deficiency, by reducing the slope of the tibial plateau angle.
      PROCEDURE: Advantages of the TWO surgery are that it does not require dedicated
      equipment and can be performed in young dogs prior to closure of the physis.
      However, it is a technically demanding procedure and the potential for
      complications is high. RESULTS: In this retrospective review of 249 dogs that had
      unilateral and 51 that had bilateral TWO surgery, the overall complication rate
      was 31.7% (95/300) and the rate of revision surgery was considerable (37 cases or
      12.33%). CONCLUSIONS: The most important clinical complications were
      postoperative medial meniscal tears, tibial fractures and implant failures,
      necessitating repeat surgery.

PMID- 19857237
TI  - Veterinarians' preferences for anticonvulsant drugs for treating seizure
      disorders in dogs and cats.
AB  - OBJECTIVE: To identify veterinarians' approaches and concerns when managing
      canine and feline patients with acute and chronic seizure disorders. DESIGN:
      Cross-sectional survey. METHOD: A questionnaire was distributed to veterinarians
      to determine how many dogs and cats they were actively treating for seizures,
      their anticonvulsant drug (ACD) preferences for treating acute and chronic
      seizure disorders and whether serum anticonvulsant concentrations and/or
      biochemical analytes were routinely measured. Additional questions involved the
      respondent's year and place of graduation and identified concerns they faced when
      managing patients with seizure disorders. RESULTS: Phenobarbitone was the most
      commonly used ACD for managing chronic seizure disorders in both dogs and cats,
      with 82% of respondents using a combination of phenobarbitone and potassium
      bromide to manage refractory seizure disorders in dogs. Most respondents (96%)
      felt comfortable managing seizures in dogs, but only 63% were comfortable
      managing affected cats. Routine monitoring of serum ACD concentrations and of
      liver biochemical analytes was performed routinely by 71% and 45% of respondents,
      respectively. Of the respondents, 86% graduated from Australian universities and
      of these 53% had graduated after 1985. CONCLUSION: Veterinarians identified when
      to commence medication, whether regular monitoring of serum ACD concentrations
      and liver enzyme activity was necessary, and if the cost was justified.
      Veterinarians also identified the need to balance dose rates and side-effects by
      using combination therapy, and the importance of providing accurate information
      to clients about what to expect in terms of seizure control for their pet.

PMID- 19857239
TI  - Case report: Spinal dermoid sinus in a Burmese cat with paraparesis.
AB  - A 2-year-old, male, Burmese cat was evaluated for chronic progressive hindlimb
      weakness, ataxia and urinary incontinence. Radiographic examination, myelography
      and magnetic resonance imaging defined congenital vertebral anomalies and a space
      occupying intradural, extramedullary mass. A dermoid sinus was subsequently
      identified dorsal to the affected spine. Surgical excision of the tract
      necessitated a dorsal laminectomy and removal of a 1-cm diameter intradural
      dermoid sinus 'cyst' that contained hair and sebaceous debris. The cat recovered
      hindlimb function after surgery and remains asymptomatic 50 months after surgery
      except for a persistent inability to urinate voluntarily.

PMID- 19857240
TI  - Clinical field study to evaluate the efficacy and safety of the amino
      acetonitrile derivative, monepantel, compared with registered anthelmintics
      against gastrointestinal nematodes of sheep in Australia.
AB  - OBJECTIVE: To determine the efficacy of monepantel, a developmental compound from
      the amino-acetonitrile derivative class of anthelmintics, against field
      infections of gastrointestinal nematodes in sheep. PROCEDURES: Comparisons of
      efficacy (using standard faecal worm egg count reduction tests) and safety (on
      the basis of visual observations) were made in a large-scale field study in
      Australia, between groups of sheep treated with either an oral solution of
      monepantel or a registered anthelmintic. The sheep were naturally infected with
      the major gastrointestinal nematode genera present in Australia. RESULTS: The
      post-treatment efficacy results for monepantel were: at 7 days (+/-1 day)
      efficacy was >98%; at 14 days (+/-1 day) it was generally close to or >99%; and
      at 21 days (+/-1 day) efficacy was consistently >99%. A high proportion of the
      targeted nematode populations were confirmed as being resistant to one or more of
      the currently available anthelmintic classes. CONCLUSIONS: Monepantel when used
      under field conditions at a minimum dose rate of 2.5 mg/kg was highly effective
      against mixed-genus natural field infections of the major gastrointestinal
      nematode genera including Haemonchus, Teladorsagia (Ostertagia),
      Trichostrongylus, Nematodirus, Chabertia and Oesophagostomum. This result
      included efficacy against some populations resistant to the currently available
      broad-spectrum anthelmintics. Few Cooperia spp. were present to allow
      confirmation of efficacy against this genus. On no occasion after treatment did
      any commercial anthelmintic-treated groups have significantly lower faecal egg
      counts than the monepantel-treated groups. Monepantel was safe for the target
      animals and human operators when used in a field situation.

PMID- 19857241
TI  - Case report: Repair of a type IV Monteggia fracture in a foal.
AB  - A Monteggia fracture is a humero-radial luxation combined with a fracture of the
      ulna. It is a rare injury, infrequently reported in the horse. This case report
      describes the surgical repair of such a fracture in a 4-month-old filly.

PMID- 19857243
TI  - Abstracts of the Royal College of Radiologists Breast Group Annual Scientific
      Meeting. Belfast, Northern Ireland. November 1-3, 2009.

PMID- 19857242
TI  - Chronic fatigue syndrome: aetiology, diagnosis and treatment.
AB  - Chronic fatigue syndrome is characterised by intense fatigue, with duration of
      over six months and associated to other related symptoms. The latter include
      asthenia and easily induced tiredness that is not recovered after a night's
      sleep. The fatigue becomes so severe that it forces a 50% reduction in daily
      activities. Given its unknown aetiology, different hypotheses have been
      considered to explain the origin of the condition (from immunological disorders
      to the presence of post-traumatic oxidative stress), although there are no
      conclusive diagnostic tests. Diagnosis is established through the exclusion of
      other diseases causing fatigue. This syndrome is rare in childhood and
      adolescence, although the fatigue symptom per se is quite common in paediatric
      patients. Currently, no curative treatment exists for patients with chronic
      fatigue syndrome. The therapeutic approach to this syndrome requires a
      combination of different therapeutic modalities. The specific characteristics of
      the symptomatology of patients with chronic fatigue require a rapid adaptation of
      the educational, healthcare and social systems to prevent the problems derived
      from current systems. Such patients require multidisciplinary management due to
      the multiple and different issues affecting them. This document was realized by
      one of the Interdisciplinary Work Groups from the Institute for Rare Diseases,
      and its aim is to point out the main social and care needs for people affected
      with Chronic Fatigue Syndrome. For this, it includes not only the view of
      representatives for different scientific societies, but also the patient
      associations view, because they know the true history of their social and
      sanitary needs. In an interdisciplinary approach, this work also reviews the
      principal scientific, medical, socio-sanitary and psychological aspects of
      Chronic Fatigue Syndrome.

PMID- 19857244
TI  - Abstracts of Frontiers of Retrovirology: Complex retroviruses, retroelements and
      their hosts. Montpellier, France. September 21-23, 2009.

PMID- 19857245
TI  - Functional characterization of the trans-membrane domain interactions of the
      Sec61 protein translocation complex beta-subunit.
AB  - BACKGROUND: In eukaryotic cells co- and post-translational protein translocation
      is mediated by the trimeric Sec61 complex. Currently, the role of the Sec61
      complex beta-subunit in protein translocation is poorly understood. We have shown
      previously that in Saccharomyces cerevisiae the trans-membrane domain alone is
      sufficient for the function of the beta-subunit Sbh1p in co-translational protein
      translocation. In addition, Sbh1p co-purifies not only with the protein
      translocation channel subunits Sec61p and Sss1p, but also with the reticulon
      family protein Rtn1p. RESULTS: We used random mutagenesis to generate novel Sbh1p
      mutants in order to functionally map the Sbh1p trans-membrane domain. These
      mutants were analyzed for their interactions with Sec61p and how they support co
      translational protein translocation. The distribution of mutations identifies one
      side of the Sbh1p trans-membrane domain alpha-helix that is involved in
      interactions with Sec61p and that is important for Sbh1p function in protein
      translocation. At the same time, these mutations do not affect Sbh1p interaction
      with Rtn1p. Furthermore we show that Sbh1p is found in protein complexes
      containing not only Rtn1p, but also the two other reticulon-like proteins Rtn2p
      and Yop1p. CONCLUSION: Our results identify functionally important amino acids in
      the Sbh1p trans-membrane domain. In addition, our results provide additional
      support for the involvement of Sec61beta in processes unlinked to protein
      translocation.

PMID- 19857246
TI  - Transforming medical professionalism to fit changing health needs.
AB  - BACKGROUND: The professional organization of medical work no longer reflects the
      changing health needs caused by the growing number of complex and chronically ill
      patients. Key stakeholders enforce coordination and remove power from the medical
      professions in order allow for these changes. However, it may also be necessary
      to initiate basic changes to way in which the medical professionals work in order
      to adapt to the changing health needs. DISCUSSION: Medical leaders, supported by
      health policy makers, can consciously activate the self-regulatory capacity of
      medical professionalism in order to transform the medical profession and the
      related professional processes of care so that it can adapt to the changing
      health needs. In doing so, they would open up additional routes to the
      improvement of the health services system and to health improvement. This
      involves three consecutive steps: (1) defining and categorizing the health needs
      of the population; (2) reorganizing the specialty domains around the needs of
      population groups; (3) reorganizing the specialty domains by eliminating work
      that could be done by less educated personnel or by the patients themselves. We
      suggest seven strategies that are required in order to achieve this
      transformation. SUMMARY: Changing medical professionalism to fit the changing
      health needs will not be easy. It will need strong leadership. But, if the
      medical world does not embark on this endeavour, good doctoring will become
      merely a bureaucratic and/or marketing exercise that obscures the ultimate goal
      of medicine which is to optimize the health of both individuals and the entire
      population.

PMID- 19857247
TI  - Assessing the intake of obesity-related foods and beverages in young children:
      comparison of a simple population survey with 24 hr-recall.
AB  - BACKGROUND: With an increasing focus on obesity prevention there is a need for
      simple, valid tools to assess dietary indicators that may be the targets of
      intervention programs. The objective of this study was to determine the relative
      validity of previous day dietary intake using a newly developed parent-proxy
      questionnaire (EPAQ) for two to five year old children. METHODS: A convenience
      sample of participants (n = 90) recruited through preschools and the community in
      Geelong, Australia provided dietary data for their child via EPAQ and interviewer
      administered 24-hour dietary recall (24 hr-recall). Comparison of mean food and
      beverage group servings between the EPAQ and 24 hr-recall was conducted and
      Spearman rank correlations were computed to examine the association between the
      two methods. RESULTS: Mean servings of food/beverage groups were comparable
      between methods for all groups except water, and significant correlations were
      found between the servings of food and beverages using the EPAQ and 24-hr recall
      methods (ranging from 0.57 to 0.88). CONCLUSION: The EPAQ is a simple and useful
      population-level tool for estimating the intake of obesity-related foods and
      beverages in children aged two to five years. When compared with 24-hour recall
      data, the EPAQ produced an acceptable level of relative validity and this short
      survey has application for population monitoring and the evaluation of population
      based obesity prevention interventions for young children.

PMID- 19857248
TI  - Superinfection occurs in Anaplasma phagocytophilum infected sheep irrespective of
      infection phase and protection status.
AB  - BACKGROUND: Anaplasma phagocytophilum infection in domestic ruminants is
      widespread in the coastal areas of southern Norway. The bacteria may persist in
      mammalian hosts. Several genetic variants of A. phagocytophilum exist. In the
      present study, we investigate whether superinfection occurs in the acute and
      persistent phase of the infection. METHODS: Five-month-old lambs of the Norwegian
      Dala breed were experimentally infected with two 16S rRNA gene variants of A.
      phagocytophilum, i.e. A. phagocytophilum variant 1 (GenBank accession number
      M73220) and variant 2 (GenBank acc. no. AF336220). Eighteen lambs were used, two
      lambs in each group. Eight groups were experimentally inoculated with either
      variant 1 or 2 on day 0. Six of these groups were then challenged with the other
      variant on either days 7, 42 or 84, respectively. One group was left uninfected.
      The occurrence of A. phagocytophilum in blood samples was determined using semi
      nested PCR analysis and gene sequencing. Specific antibodies were measured by an
      indirect immunofluorescence antibody assay (IFA). RESULTS: A. phagocytophilum
      variant 1 and 2 differed significantly with regards to clinical reaction and
      cross-immunity in infected lambs. Both variants were found in the blood after
      challenge. However, variant 1 was detected most frequently. CONCLUSION: The
      present experiment indicates that superinfection of different genotypes occurs
      during the acute as well as the persistent phase of an A. phagocytophilum
      infection, even in lambs protected against the challenged infection.

PMID- 19857249
TI  - Use of complementary and alternative medicine: a survey in Turkish
      gastroenterology patients.
AB  - BACKGROUND: The study examined complementary and alternative medicine (CAM) usage
      by patients attending a Turkish gastroenterology outpatient clinic. METHODS: The
      survey was conducted on 216 patients presenting with gastrointestinal problems
      during their first visit to the clinic using a 31 item, self-report questionnaire
      between May and October 2005. Data included information on patient demographics
      and their gastrointestinal symptoms, as well as items to identify CAM use and
      patient satisfaction with these therapies. RESULTS: Seventy-nine patients (36.6%)
      reported using one or more forms of CAM. The most commonly used therapy was
      herbal therapy, usually taken as a tea or infusion. These were used by 27 people
      (29%) in this subgroup. Common indicators for their use were epigastric pain,
      constipation, bloating and dyspepsia or indigestion. CAM use among upper GI
      patients was marginally higher than lower GI patients (41.8% versus 41.2%), but
      the highest usage was amongst patients with liver disease where 53.8% reported
      using one or more CAM therapy. About half of the patients learned about CAM from
      their relatives or friends, with more women than men using the therapies (p <
      0.05). Clinical characteristics such as diagnosis, duration of symptoms and prior
      surgical intervention did not differ between users and non-users of CAM
      therapies. Multivariate analysis showed that being female and higher educational
      status were positively associated with CAM usage (p < 0.05). CONCLUSION: CAM
      usage in our sample of gastrointestinal patients was lower than that described in
      other countries and other chronic disease groups. This could be due to their low
      perceived efficacy, or the relatively transient duration of symptoms experienced
      by the sample. Healthcare professionals need however, to be aware of CAM usage in
      order to educate patients appropriately about possible adverse effects or drug
      interactions.

PMID- 19857250
TI  - Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell
      carcinoma.
AB  - BACKGROUND: The ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) gene involved in
      the regulation of cellular ubiquitin levels plays an important role in different
      cellular processes including cell growth and differentiation. Aberrant expression
      of UCHL1 has been found in a number of human solid tumors including renal cell
      carcinoma (RCC). In RCC, UCHL1 overexpression is associated with tumor
      progression and an altered von Hippel Lindau gene expression. METHODS: To
      determine the underlying mechanisms for the heterogeneous UCHL1 expression
      pattern in RCC the UCHL1 promoter DNA methylation status was determined in 17 RCC
      cell lines as well as in 32 RCC lesions and corresponding tumor adjacent kidney
      epithelium using combined bisulfite restriction analysis as well as bisulfite DNA
      sequencing. RESULTS: UCHL1 expression was found in all 32 tumor adjacent kidney
      epithelium samples. However, the lack of or reduced UCHL1 mRNA and/or protein
      expression was detected in 13/32 RCC biopsies and 7/17 RCC cell lines and due to
      either a total or partial methylation of the UCHL1 promoter DNA. Upon 2'-deoxy-5
      azacytidine treatment an induction of UCHL1 mRNA and protein expression was found
      in 9/17 RCC cell lines, which was linked to the demethylation degree of the UCHL1
      promoter DNA. CONCLUSION: Promoter hypermethylation represents a mechanism for
      the silencing of the UCHL1 gene expression in RCC and supports the concept of an
      epigenetic control for the expression of UCHL1 during disease progression.

PMID- 19857252
TI  - Graduates from a traditional medical curriculum evaluate the effectiveness of
      their medical curriculum through interviews.
AB  - BACKGROUND: In 1996 The University of Liverpool reformed its medical course from
      a traditional lecture-based course to an integrated PBL curriculum. A project has
      been underway since 2000 to evaluate this change. Part of this project has
      involved gathering retrospective views on the relevance of both types of
      undergraduate education according to graduates. This paper focuses on the views
      of traditional Liverpool graduates approximately 6 years after graduation.
      METHODS: From February 2006 to June 2006 interviews took place with 46 graduates
      from the last 2 cohorts to graduate from the traditional Liverpool curriculum.
      RESULTS: The graduates were generally happy with their undergraduate education
      although they did feel there were some flaws in their curriculum. They felt they
      had picked up good history and examination skills and were content with their
      exposure to different specialties on clinical attachments. They were also pleased
      with their basic science teaching as preparation for postgraduate exams, however
      many complained about the overload and irrelevance of many lectures in the early
      years of their course, particular in biochemistry. There were many different
      views about how they integrated this science teaching into understanding disease
      processes and many didn't feel it was made relevant to them at the time they
      learned it. Retrospectively, they felt that they hadn't been clinically well
      prepared for the role of working as junior doctor, particularly the practical
      aspects of the job nor had enough exposure to research skills. Although there was
      little communication skills training in their course they didn't feel they would
      have benefited from this training as they managed to pick up had the required
      skills on clinical attachments. CONCLUSION: These interviews offer a historical
      snapshot of the views of graduates from a traditional course before many courses
      were reformed. There was some conflict in the interviews about the doctors
      enjoying their undergraduate education but then saying that they didn't feel they
      received good preparation for working as a junior doctor. Although the graduates
      were happy with their undergraduate education these interviews do highlight some
      of the reasons why the traditional curriculum was reformed at Liverpool.

PMID- 19857253
TI  - Monopolar teres major muscle transposition to improve shoulder abduction and
      flexion in children with sequelae of obstetric brachial plexus palsy.
AB  - We present a new surgical technique for a pedicled teres major muscle transfer to
      improve shoulder abduction and flexion in children with sequelae of obstetric
      brachial plexus palsy. In addition, we provide the clinical outcome in the first
      17 operated children.

PMID- 19857251
TI  - Classification of Myoviridae bacteriophages using protein sequence similarity.
AB  - BACKGROUND: We advocate unifying classical and genomic classification of
      bacteriophages by integration of proteomic data and physicochemical parameters.
      Our previous application of this approach to the entirely sequenced members of
      the Podoviridae fully supported the current phage classification of the
      International Committee on Taxonomy of Viruses (ICTV). It appears that horizontal
      gene transfer generally does not totally obliterate evolutionary relationships
      between phages. RESULTS: CoreGenes/CoreExtractor proteome comparison techniques
      applied to 102 Myoviridae suggest the establishment of three subfamilies
      (Peduovirinae, Teequatrovirinae, the Spounavirinae) and eight new independent
      genera (Bcep781, BcepMu, FelixO1, HAP1, Bzx1, PB1, phiCD119, and phiKZ-like
      viruses). The Peduovirinae subfamily, derived from the P2-related phages, is
      composed of two distinct genera: the "P2-like viruses", and the "HP1-like
      viruses". At present, the more complex Teequatrovirinae subfamily has two genera,
      the "T4-like" and "KVP40-like viruses". In the genus "T4-like viruses" proper,
      four groups sharing >70% proteins are distinguished: T4-type, 44RR-type, RB43
      type, and RB49-type viruses. The Spounavirinae contain the "SPO1-"and "Twort-like
      viruses." CONCLUSION: The hierarchical clustering of these groupings provide
      biologically significant subdivisions, which are consistent with our previous
      analysis of the Podoviridae.

PMID- 19857254
TI  - Automatic noninvasive measurement of systolic blood pressure using
      photoplethysmography.
AB  - BACKGROUND: Automatic measurement of arterial blood pressure is important, but
      the available commercial automatic blood pressure meters, mostly based on
      oscillometry, are of low accuracy. METHODS: In this study, we present a cuff
      based technique for automatic measurement of systolic blood pressure, based on
      photoplethysmographic signals measured simultaneously in fingers of both hands.
      After inflating the pressure cuff to a level above systolic blood pressure in a
      relatively slow rate, it is slowly deflated. The cuff pressure for which the
      photoplethysmographic signal reappeared during the deflation of the pressure-cuff
      was taken as the systolic blood pressure. The algorithm for the detection of the
      photoplethysmographic signal involves: (1) determination of the time-segments in
      which the photoplethysmographic signal distal to the cuff is expected to appear,
      utilizing the photoplethysmographic signal in the free hand, and (2)
      discrimination between random fluctuations and photoplethysmographic pattern. The
      detected pulses in the time-segments were identified as photoplethysmographic
      pulses if they met two criteria, based on the pulse waveform and on the
      correlation between the signal in each segment and the signal in the two
      neighboring segments. RESULTS: Comparison of the photoplethysmographic-based
      automatic technique to sphygmomanometry, the reference standard, shows that the
      standard deviation of their differences was 3.7 mmHg. For subjects with systolic
      blood pressure above 130 mmHg the standard deviation was even lower, 2.9 mmHg.
      These values are much lower than the 8 mmHg value imposed by AAMI standard for
      automatic blood pressure meters. CONCLUSION: The photoplethysmographic-based
      technique for automatic measurement of systolic blood pressure, and the algorithm
      which was presented in this study, seems to be accurate.

PMID- 19857255
TI  - Exploring the molecular basis of insecticide resistance in the dengue vector
      Aedes aegypti: a case study in Martinique Island (French West Indies).
AB  - BACKGROUND: The yellow fever mosquito Aedes aegypti is a major vector of dengue
      and hemorrhagic fevers, causing up to 100 million dengue infections every year.
      As there is still no medicine and efficient vaccine available, vector control
      largely based on insecticide treatments remains the only method to reduce dengue
      virus transmission. Unfortunately, vector control programs are facing operational
      challenges with mosquitoes becoming resistant to commonly used insecticides.
      Resistance of Ae. aegypti to chemical insecticides has been reported worldwide
      and the underlying molecular mechanisms, including the identification of enzymes
      involved in insecticide detoxification are not completely understood. RESULTS:
      The present paper investigates the molecular basis of insecticide resistance in a
      population of Ae. aegypti collected in Martinique (French West Indies). Bioassays
      with insecticides on adults and larvae revealed high levels of resistance to
      organophosphate and pyrethroid insecticides. Molecular screening for common
      insecticide target-site mutations showed a high frequency (71%) of the sodium
      channel 'knock down resistance' (kdr) mutation. Exposing mosquitoes to
      detoxification enzymes inhibitors prior to bioassays induced a significant
      increased susceptibility of mosquitoes to insecticides, revealing the presence of
      metabolic-based resistance mechanisms. This trend was biochemically confirmed by
      significant elevated activities of cytochrome P450 monooxygenases, glutathione S
      transferases and carboxylesterases at both larval and adult stages. Utilization
      of the microarray Aedes Detox Chip containing probes for all members of
      detoxification and other insecticide resistance-related enzymes revealed the
      significant constitutive over-transcription of multiple detoxification genes at
      both larval and adult stages. The over-transcription of detoxification genes in
      the resistant strain was confirmed by using real-time quantitative RT-PCR.
      CONCLUSION: These results suggest that the high level of insecticide resistance
      found in Ae. aegypti mosquitoes from Martinique island is the consequence of both
      target-site and metabolic based resistance mechanisms. Insecticide resistance
      levels and associated mechanisms are discussed in relation with the environmental
      context of Martinique Island. These finding have important implications for
      dengue vector control in Martinique and emphasizes the need to develop new tools
      and strategies for maintaining an effective control of Aedes mosquito populations
      worldwide.

PMID- 19857256
TI  - Association between an 8q24 locus and the risk of colorectal cancer in Japanese.
AB  - BACKGROUND: A genome-wide association study (GWAS), which assessed multiple
      ethnicities, reported an association between single nucleotide polymorphisms in
      the 8q24 region and colorectal cancer risk. Although the association with the
      identified loci was strong, information on its impact in combination with
      lifestyle factors is limited. METHODS: We conducted a case-control study in 481
      patients with colorectal cancer (CRC) and 962 sex-age matched non-cancer
      controls. Data on lifestyle factors, including diet, were obtained by self
      administered questionnaire. Two 8q24 loci, rs6983267 and rs10090154, were
      assessed by the TaqMan method. Associations were then assessed by multivariate
      logistic regression models that considered potential confounders. RESULTS: We
      found an increased risk of CRC with rs6983267 but not with rs10090154. An allelic
      OR was 1.22 (1.04-1.44, p for trend = 0.014), which remained significant after
      adjustment for confounders (OR = 1.25). No statistically significant interaction
      with potential confounding factors was observed. CONCLUSION: The polymorphism
      rs6983267 showed a significant association with CRC in a Japanese population.
      Further investigation of the biological mechanism of this association is
      warranted.

PMID- 19857257
TI  - Comparative analysis of medicinal plants used in traditional medicine in Italy
      and Tunisia.
AB  - BACKGROUND: Italy and Tunisia (Africa for the Romans), facing each other on the
      opposite sides of the Mediterranean Sea, have been historically linked since the
      ancient times. Over the centuries both countries were mutually dominated so the
      vestiges and traces of a mutual influence are still present. The aim of the
      present study is to conduct a comparative analysis of the medicinal species
      present in the respective Floras in order to explore potential analogies and
      differences in popular phytotherapy that have come out from those reciprocal
      exchanges having taken place over the centuries METHODS: The comparative analysis
      based on the respective floras of both countries takes into consideration the
      bulk of medicinal species mutually present in Italy and Tunisia, but it focuses
      on the species growing in areas which are similar in climate. The medicinal uses
      of these species are considered in accordance with the ethnobotanical literature.
      RESULTS: A list of 153 medicinal species belonging to 60 families, present in
      both floras and used in traditional medicine, was drawn. A considerable
      convergence in therapeutic uses of many species emerged from these data.
      CONCLUSION: This comparative analysis strengthens the firm belief that ethno
      botanical findings represent not only an important shared heritage, developed
      over the centuries, but also a considerable mass of data that should be exploited
      in order to provide new and useful knowledge.

PMID- 19857258
TI  - Seasonal distribution of Anopheles funestus chromosomal forms from Burkina Faso.
AB  - BACKGROUND: Previous studies of Anopheles funestus chromosomal inversion
      polymorphisms in Burkina Faso showed large departures from Hardy-Weinberg
      equilibrium and linkage disequilibrium among inversions located on different
      chromosomes, implying the existence of two taxonomic units ("chromosomal forms")
      with limited genetic flow. One chromosomal form, named Folonzo, is highly
      polymorphic for alternative rearrangements of 3Ra, 3Rb, 2Ra, and 3La; the other,
      Kiribina, is predominantly characterized by the standard arrangement of these
      inversions. To investigate the temporal distribution of these chromosomal forms,
      further collections were carried out in two villages near Ouagadougou where they
      are found in sympatry. METHODS: Chromosomal karyotypes were determined from
      indoor-resting, half-gravid females sampled within and across six breeding
      seasons, from December 1998 to April 2007. RESULTS: As expected, the pattern of
      chromosomal polymorphism in An. funestus was consistent with assortatively mating
      Folonzo and Kiribina forms. When samples were assigned to each chromosomal form,
      their relative abundance varied within successive breeding seasons in a repeating
      pattern of temporal variability. Relative abundance of the Folonzo form was
      correlated with climatic variables related to temperature and rainfall.
      CONCLUSION: The relative abundance of Folonzo and Kiribina forms of An. funestus
      likely reflects different larval ecologies that are linked to varying climatic
      conditions. Further analysis of the bionomics of these vectors is recommended in
      light of its relevance to vector control.

PMID- 19857260
TI  - TRPV6 alleles do not influence prostate cancer progression.
AB  - BACKGROUND: The transient receptor potential, subfamily V, member 6 (TRPV6) is a
      Ca(2+) selective cation channel. Several studies have shown that TRPV6
      transcripts are expressed in locally advanced prostatic adenocarcinoma,
      metastatic and androgen-insensitive prostatic lesions but are undetectable in
      healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of
      the human trpv6 gene have been identified which are transcribed into two
      independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is
      correlated with the onset of prostate cancer, with the Gleason score and the
      tumour stage. METHODS: Genomic DNA of prostate cancer patients and control
      individuals was isolated from resections of prostatic adenocarcinomas and
      salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed
      by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR
      was isolated from prostate tissue. Data sets were analyzed by Chi-Square test.
      RESULTS: We first characterized in detail the five polymorphisms present in the
      protein coding exons of the trpv6 gene and show that these polymorphisms are
      coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed
      the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of
      169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%,
      whereas no homozygous TRPV6a carriers could be identified. The International
      HapMap Project identified a similar frequency for an Utah based population
      whereas in an African population the a-genotype prevailed. The incidence of
      prostate cancer is several times higher in African populations than in non
      African and we then investigated the TRPV6a/b frequencies in 141 samples of
      prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples
      without correlation with Gleason score and tumour stage. CONCLUSION: Our results
      show that the frequencies of trpv6 alleles in healthy control individuals and
      prostate cancer patients are not significantly different. Although expression of
      trpv6 transcripts correlates with aggressive potential of prostate cancer, the
      TRPV6 genotype does not correlate with the onset of prostate cancer, with the
      Gleason score and the tumour stage.

PMID- 19857261
TI  - Partially-supervised protein subclass discovery with simultaneous annotation of
      functional residues.
AB  - BACKGROUND: The study of functional subfamilies of protein domain families and
      the identification of the residues which determine substrate specificity is an
      important question in the analysis of protein domains. One way to address this
      question is the use of clustering methods for protein sequence data and
      approaches to predict functional residues based on such clusterings. The
      locations of putative functional residues in known protein structures provide
      insights into how different substrate specificities are reflected on the protein
      structure level. RESULTS: We have developed an extension of the context-specific
      independence mixture model clustering framework which allows for the integration
      of experimental data. As these are usually known only for a few proteins, our
      algorithm implements a partially-supervised learning approach. We discover domain
      subfamilies and predict functional residues for four protein domain families:
      phosphatases, pyridoxal dependent decarboxylases, WW and SH3 domains to
      demonstrate the usefulness of our approach. CONCLUSION: The partially-supervised
      clustering revealed biologically meaningful subfamilies even for highly
      heterogeneous domains and the predicted functional residues provide insights into
      the basis of the different substrate specificities.

PMID- 19857262
TI  - Tissue-specific cytokine release from human extra-placental membranes stimulated
      by lipopolysaccharide in a two-compartment tissue culture system.
AB  - BACKGROUND: The extra-placental gestational membranes secrete cytokines in
      response to bacteria and other infectious agents, with potentially adverse
      consequences for pregnancy. The present study used lipopolysaccharide (LPS) as a
      prototype endotoxin to investigate the pattern of stimulated cytokine release
      from the amniotic and choriodecidual sides of full-thickness human gestational
      membranes in a two-compartment tissue culture system. METHODS: Gestational
      membranes were collected from healthy non-laboring caesarean deliveries at term.
      Full-thickness membranes from each placenta were cut into pieces, mounted on
      Transwell frames, and placed in culture wells to create a two-compartment culture
      with the gestational membranes serving as the barrier between compartments. The
      LPS (100 ng/ml) was added to the amniotic, choriodecidual or both chambers of the
      culture, and cytokines were assayed in the medium of the amniotic and
      choriodecidual chambers after 8 h of LPS exposure. Cytokine concentrations were
      analyzed by two-way analysis of variance for effects of treatment and side
      specificity of cytokine release from the membranes. RESULTS: LPS exposure on the
      choriodecidual side of the membranes significantly increased TNF-alpha, IL-6, IL
      10 and IL-8 in the choriodecidual compartment, whereas TNF-alpha was the only
      cytokine observed to increase in the amniotic compartment. When LPS treatment was
      to the amniotic side of the membranes, there were significant increases in TNF
      alpha and IL-6 in the amniotic compartment as well as increased concentrations of
      TNF-alpha, IL-6 and IL-8 in the choriodecidual compartment; however, there were
      no statistically significant differences for IL-10 in either compartment. No
      statistically significant differences were observed for IL-1beta, TGF-beta or IL
      4 concentrations in response to LPS, regardless of the exposure modality.
      CONCLUSION: The amnion and choriodecidua exhibited distinct patterns of response
      to LPS with evidence of inflammatory signaling across the layers of the
      gestational membranes. These results suggest a complicated network of signaling
      within the gestational membranes, in which cytokine- and tissue-specific
      responses to inflammatory stimulation may have important implications for
      maintaining pregnancy in the challenge of microbial invasion of the uterine
      compartment.

PMID- 19857263
TI  - Transcriptome analysis of differentiating trypanosomes reveals the existence of
      multiple post-transcriptional regulons.
AB  - BACKGROUND: Trypanosome gene expression is regulated almost exclusively at the
      post-transcriptional level, with mRNA degradation playing a decisive role. When
      trypanosomes are transferred from the blood of a mammal to the midgut of a Tsetse
      fly, they transform to procyclic forms: gene expression is reprogrammed, changing
      the cell surface and switching the mode of energy metabolism. Within the blood,
      trypanosomes can pre-adapt for Tsetse transmission, becoming growth-arrested
      stumpy forms. We describe here the transitions in gene expression that occur
      during differentiation of in-vitro cultured bloodstream forms to procyclic forms.
      RESULTS: Some mRNAs showed changes within 30 min of cis-aconitate addition,
      whereas others responded 12-24 hours later. For the first 12 h after addition of
      cis-aconitate, cells accumulated at the G1 phase of the cell cycle, and showed
      decreases in mRNAs required for proliferation, mimicking the changes seen in
      stumpy forms: many mRNAs needed for ribosomal and flagellar biogenesis showed
      striking co-regulation. Other mRNAs encoding components of signal transduction
      pathways and potential regulators were specifically induced only during
      differentiation. Messenger RNAs encoding proteins required for individual
      metabolic pathways were often co-regulated. CONCLUSION: Trypanosome genes form
      post-transcriptional regulons in which mRNAs with functions in particular
      pathways, or encoding components of protein complexes, show almost identical
      patterns of regulation.

PMID- 19857264
TI  - Mid-term results and factors affecting outcome of a metal-backed unicompartmental
      knee design: a case series.
AB  - BACKGROUND: Controversies exist regarding the indications for unicompartmental
      knee arthroplasty. The objective of this study is to report the mid-term results
      and examine predictors of failure in a metal-backed unicompartmental knee
      arthroplasty design. METHODS: At a mean follow-up of 60 months, 80 medial
      unicompartmental knee arthroplasties (68 patients) were evaluated. Implant
      survivorship was analyzed using Kaplan-Meier method. The Knee Society objective
      and functional scores and radiographic characteristics were compared before
      surgery and at final follow-up. A Cox proportional hazard model was used to
      examine the association of patient's age, gender, obesity (body mass index > 30
      kg/m2), diagnosis, Knee Society scores and patella arthrosis with failure.
      RESULTS: There were 9 failures during the follow up. The mean Knee Society
      objective and functional scores were respectively 49 and 48 points preoperatively
      and 95 and 92 points postoperatively. The survival rate was 92% at 5 years and
      84% at 10 years. The mean age was younger in the failure group than the non
      failure group (p < 0.01). However, none of the factors assessed was independently
      associated with failure based on the results from the Cox proportional hazard
      model. CONCLUSION: Gender, pre-operative diagnosis, preoperative objective and
      functional scores and patellar osteophytes were not independent predictors of
      failure of unicompartmental knee implants, although high body mass index trended
      toward significance. The findings suggest that the standard criteria for UKA may
      be expanded without compromising the outcomes, although caution may be warranted
      in patients with very high body mass index pending additional data to confirm our
      results. LEVEL OF EVIDENCE: IV.

PMID- 19857265
TI  - Bayesian modeling of ChIP-chip data using latent variables.
AB  - BACKGROUND: The ChIP-chip technology has been used in a wide range of biomedical
      studies, such as identification of human transcription factor binding sites,
      investigation of DNA methylation, and investigation of histone modifications in
      animals and plants. Various methods have been proposed in the literature for
      analyzing the ChIP-chip data, such as the sliding window methods, the hidden
      Markov model-based methods, and Bayesian methods. Although, due to the integrated
      consideration of uncertainty of the models and model parameters, Bayesian methods
      can potentially work better than the other two classes of methods, the existing
      Bayesian methods do not perform satisfactorily. They usually require multiple
      replicates or some extra experimental information to parametrize the model, and
      long CPU time due to involving of MCMC simulations. RESULTS: In this paper, we
      propose a Bayesian latent model for the ChIP-chip data. The new model mainly
      differs from the existing Bayesian models, such as the joint deconvolution model,
      the hierarchical gamma mixture model, and the Bayesian hierarchical model, in two
      respects. Firstly, it works on the difference between the averaged treatment and
      control samples. This enables the use of a simple model for the data, which
      avoids the probe-specific effect and the sample (control/treatment) effect. As a
      consequence, this enables an efficient MCMC simulation of the posterior
      distribution of the model, and also makes the model more robust to the outliers.
      Secondly, it models the neighboring dependence of probes by introducing a latent
      indicator vector. A truncated Poisson prior distribution is assumed for the
      latent indicator variable, with the rationale being justified at length.
      CONCLUSION: The Bayesian latent method is successfully applied to real and ten
      simulated datasets, with comparisons with some of the existing Bayesian methods,
      hidden Markov model methods, and sliding window methods. The numerical results
      indicate that the Bayesian latent method can outperform other methods, especially
      when the data contain outliers.

PMID- 19857266
TI  - Evaluation of effectiveness of class-based nutrition intervention on changes in
      soft drink and milk consumption among young adults.
AB  - BACKGROUND: During last few decades, soft drink consumption has steadily
      increased while milk intake has decreased. Excess consumption of soft drinks and
      low milk intake may pose risks of several diseases such as dental caries,
      obesity, and osteoporosis. Although beverage consumption habits form during young
      adulthood, which has a strong impact on beverage choices in later life, nutrition
      education programs on beverages are scarce in this population. The purpose of
      this investigation was 1) to assess soft drink and milk consumption and 2) to
      evaluate the effectiveness of 15-week class-based nutrition intervention in
      changing beverage choices among college students. METHODS: A total of 80 college
      students aged 18 to 24 years who were enrolled in basic nutrition class
      participated in the study. Three-day dietary records were collected, verified,
      and analyzed before and after the intervention. Class lectures focused on
      healthful dietary choices related to prevention of chronic diseases and were
      combined with interactive hands on activities and dietary feedback. RESULTS:
      Class-based nutrition intervention combining traditional lecture and interactive
      activities was successful in decreasing soft drink consumption. Total milk
      consumption, specifically fat free milk, increased in females and male students
      changed milk choice favoring skim milk over low fat milk. (1% and 2%).
      CONCLUSION: Class-based nutrition education focusing on prevention of chronic
      diseases can be an effective strategy in improving both male and female college
      students' beverage choices. Using this type of intervention in a general
      nutrition course may be an effective approach to motivate changes in eating
      behaviors in a college setting.

PMID- 19857268
TI  - Time warping of evolutionary distant temporal gene expression data based on noise
      suppression.
AB  - BACKGROUND: Comparative analysis of genome wide temporal gene expression data has
      a broad potential area of application, including evolutionary biology,
      developmental biology, and medicine. However, at large evolutionary distances,
      the construction of global alignments and the consequent comparison of the time
      series data are difficult. The main reason is the accumulation of variability in
      expression profiles of orthologous genes, in the course of evolution. RESULTS: We
      applied Pearson distance matrices, in combination with other noise-suppression
      techniques and data filtering to improve alignments. This novel framework
      enhanced the capacity to capture the similarities between the temporal gene
      expression datasets separated by large evolutionary distances. We aligned and
      compared the temporal gene expression data in budding (Saccharomyces cerevisiae)
      and fission (Schizosaccharomyces pombe) yeast, which are separated by more then
      approximately 400 myr of evolution. We found that the global alignment (time
      warping) properly matched the duration of cell cycle phases in these distant
      organisms, which was measured in prior studies. At the same time, when applied to
      individual ortholog pairs, this alignment procedure revealed groups of genes with
      distinct alignments, different from the global alignment. CONCLUSION: Our
      alignment-based predictions of differences in the cell cycle phases between the
      two yeast species were in a good agreement with the existing data, thus
      supporting the computational strategy adopted in this study. We propose that the
      existence of the alternative alignments, specific to distinct groups of genes,
      suggests presence of different synchronization modes between the two organisms
      and possible functional decoupling of particular physiological gene networks in
      the course of evolution.

PMID- 19857267
TI  - Microstructure and mineral composition of dystrophic calcification associated
      with the idiopathic inflammatory myopathies.
AB  - INTRODUCTION: Calcified deposits (CDs) in skin and muscles are common in juvenile
      dermatomyositis (DM), and less frequent in adult DM. Limited information exists
      about the microstructure and composition of these deposits, and no information is
      available on their elemental composition and contents, mineral density (MD) and
      stiffness. We determined the microstructure, chemical composition, MD and
      stiffness of CDs obtained from DM patients. METHODS: Surgically-removed
      calcinosis specimens were analyzed with fourier transform infrared
      microspectroscopy in reflectance mode (FTIR-RM) to map their spatial distribution
      and composition, and with scanning electron microscopy/silicon drift detector
      energy dispersive X-ray spectrometry (SEM/SDD-EDS) to obtain elemental maps. X
      ray diffraction (XRD) identified their mineral structure, X-ray micro-computed
      tomography (microCT) mapped their internal structure and 3D distribution,
      quantitative backscattered electron (qBSE) imaging assessed their morphology and
      MD, nanoindentation measured their stiffness, and polarized light microscopy
      (PLM) evaluated the organic matrix composition. RESULTS: Some specimens were
      composed of continuous carbonate apatite containing small amounts of proteins
      with a mineral to protein ratio much higher than in bone, and other specimens
      contained scattered agglomerates of various sizes with similar composition (FTIR
      RM). Continuous or fragmented mineralization was present across the entire
      specimens (microCT). The apatite was much more crystallized than bone and dentin,
      and closer to enamel (XRD) and its calcium/phosphorous ratios were close to
      stoichiometric hydroxyapatite (SEM/SDD-EDS). The deposits also contained
      magnesium and sodium (SEM/SDD-EDS). The MD (qBSE) was closer to enamel than bone
      and dentin, as was the stiffness (nanoindentation) in the larger dense patches.
      Large mineralized areas were typically devoid of collagen; however, collagen was
      noted in some regions within the mineral or margins (PLM). qBSE, FTIR-RM and
      SEM/SDD-EDS maps suggest that the mineral is deposited first in a fragmented
      pattern followed by a wave of mineralization that incorporates these particles.
      Calcinosis masses with shorter duration appeared to have islands of
      mineralization, whereas longstanding deposits were solidly mineralized.
      CONCLUSIONS: The properties of the mineral present in the calcinosis masses are
      closest to that of enamel, while clearly differing from bone. Calcium and
      phosphate, normally present in affected tissues, may have precipitated as
      carbonate apatite due to local loss of mineralization inhibitors.

PMID- 19857269
TI  - Influence of the calcium concentration in the presence of organic phosphorus on
      the physicochemical compatibility and stability of all-in-one admixtures for
      neonatal use.
AB  - BACKGROUND: Preterm infants need high amounts of calcium and phosphorus for bone
      mineralization, which is difficult to obtain with parenteral feeding due to the
      low solubility of these salts. The objective of this study was to evaluate the
      physicochemical compatibility of high concentrations of calcium associated with
      organic phosphate and its influence on the stability of AIO admixtures for
      neonatal use. METHODS: Three TPN admixture formulas were prepared in multilayered
      bags. The calcium content of the admixtures was adjusted to 0, 46.5 or 93 mg/100
      ml in the presence of a fixed organic phosphate concentration as well as lipids,
      amino acids, inorganic salts, glucose, vitamins and oligoelements at pH 5.5. Each
      admixture was stored at 4 degrees C, 25 degrees C or 37 degrees C and evaluated
      over a period of 7 days. The physicochemical stability parameters evaluated were
      visual aspect, pH, sterility, osmolality, peroxide formation, precipitation, and
      the size of lipid globules. RESULTS: Color alterations occurred from the first
      day on, and reversible lipid film formation from the third day of study for the
      admixtures stored at 25 degrees C and 37 degrees C. According to the parameters
      evaluated, the admixtures were stable at 4 degrees C; and none of them presented
      precipitated particles due to calcium/phosphate incompatibility or lipid globules
      larger than 5 mum, which is the main parameter currently used to evaluate lipid
      emulsion stability. The admixtures maintained low peroxide levels and osmolarity
      was appropriate for parenteral administration. CONCLUSION: The total calcium and
      calcium/phosphorus ratios studied appeared not to influence the physicochemical
      compatibility and stability of AIO admixtures.

PMID- 19857270
TI  - Successful establishment of primary small airway cell cultures in human lung
      transplantation.
AB  - BACKGROUND: The study of small airway diseases such as post-transplant
      bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in
      assessing peripheral airway function either physiologically or directly. Our aims
      were to develop robust methods for sampling small airway epithelial cells (SAEC)
      and to establish submerged SAEC cultures for downstream experimentation. METHODS:
      SAEC were obtained at 62 post-transplant bronchoscopies in 26 patients using
      radiologically guided bronchial brushings. Submerged cell cultures were
      established and SAEC lineage was confirmed using expression of clara cell
      secretory protein (CCSP). RESULTS: The cell yield for SAEC (0.956 +/- 0.063 x
      106) was lower than for large airway cells (1.306 +/- 0.077 x 106) but did not
      significantly impact on the culture establishment rate (79.0 +/- 5.2% vs. 83.8 +/
      4.7% p = 0.49). The presence of BOS significantly compromised culture success
      (independent of cell yield) for SAEC (odds ratio (95%CI) 0.067 (0.01-0.40)) but
      not LAEC (0.3 (0.05-1.9)). Established cultures were successfully passaged and
      expanded. CONCLUSION: Primary SAEC can be successfully obtained from human lung
      transplant recipients and maintained in culture for downstream experimentation.
      This technique will facilitate the development of primary in vitro models for BOS
      and other diseases with a small airway component such as asthma, cystic fibrosis
      and COPD.

PMID- 19857271
TI  - The SR protein family.
AB  - SUMMARY: The processing of pre-mRNAs is a fundamental step required for the
      expression of most metazoan genes. Members of the family of serine/arginine (SR)
      rich proteins are critical components of the machineries carrying out these
      essential processing events, highlighting their importance in maintaining
      efficient gene expression. SR proteins are characterized by their ability to
      interact simultaneously with RNA and other protein components via an RNA
      recognition motif (RRM) and through a domain rich in arginine and serine
      residues, the RS domain. Their functional roles in gene expression are
      surprisingly diverse, ranging from their classical involvement in constitutive
      and alternative pre-mRNA splicing to various post-splicing activities, including
      mRNA nuclear export, nonsense-mediated decay, and mRNA translation. These
      activities point up the importance of SR proteins during the regulation of mRNA
      metabolism.

PMID- 19857273
TI  - Appearance of E1: A226V mutant Chikungunya virus in Coastal Karnataka, India
      during 2008 outbreak.
AB  - Chikungunya has resurged in the form of unprecedented explosive epidemic in 2006
      after a long gap in India affecting 1.39 million of persons. The disease
      continued for the next two consecutive years affecting 59,535 and 64,548 persons
      during 2007 and 2008 respectively. The 2008 outbreak being the second largest
      among these three years the information regarding the etiology and the mutations
      involved are useful for further control measures. Among the 2008 outbreaks the
      Coastal Karnataka accounts for the 46,510 persons. An in-depth investigation of
      Chikungunya epidemic of Coastal Karnataka, India, 2008 by serology, virus
      isolation, RT-PCR and genome sequencing revealed the presence and continued
      circulation of A226V mutant Chikungunya virus. The appearance of this mutant
      virus was found to be associated with higher prevalence of vector Aedes
      albopictus and the geographical proximity of coastal Karnataka with the adjoining
      Kerala state. This is the first report regarding the appearance of this mutation
      in Karnataka state of India. The present study identified the presence and
      association of A226V mutant virus with Chikungunya outbreak in India during 2008.

PMID- 19857272
TI  - TGF-beta1 induced epithelial to mesenchymal transition (EMT) in human bronchial
      epithelial cells is enhanced by IL-1beta but not abrogated by corticosteroids.
AB  - BACKGROUND: Chronic persistent asthma is characterized by ongoing airway
      inflammation and airway remodeling. The processes leading to airway remodeling
      are poorly understood, and there is increasing evidence that even aggressive anti
      inflammatory therapy does not completely prevent this process. We sought to
      investigate whether TGFbeta1 stimulates bronchial epithelial cells to undergo
      transition to a mesenchymal phenotype, and whether this transition can be
      abrogated by corticosteroid treatment or enhanced by the pro-inflammatory
      cytokine IL-1beta. METHODS: BEAS-2B and primary normal human bronchial epithelial
      cells were stimulated with TGFbeta1 and expression of epithelial and mesenchymal
      markers assessed by quantitative real-time PCR, immunoblotting,
      immunofluorescence microscopy and zymography. In some cases the epithelial cells
      were also incubated with corticosteroids or IL-1beta. Results were analyzed using
      non-parametric statistical tests. RESULTS: Treatment of BEAS-2B or primary human
      bronchial epithelial cells with TGFbeta1 significantly reduced the expression
      level of the epithelial adherence junction protein E-cadherin. TGFbeta1 then
      markedly induced mesenchymal marker proteins such as collagen I, tenascin C,
      fibronectin and alpha-smooth muscle actin mRNA in a dose dependant manner. The
      process of mesenchymal transition was accompanied by a morphological change
      towards a more spindle shaped fibroblast cell type with a more motile and
      invasive phenotype. Corticosteroid pre-treatment did not significantly alter the
      TGFbeta1 induced transition but IL-1beta enhanced the transition. CONCLUSION: Our
      results indicate, that TGFbeta1 can induce mesenchymal transition in the
      bronchial epithelial cell line and primary cells. Since asthma has been strongly
      associated with increased expression of TGFbeta1 in the airway, epithelial to
      mesenchymal transition may contribute to the contractile and fibrotic remodeling
      process that accompanies chronic asthma.

PMID- 19857276
TI  - [Hepatic encephalopathy following a Whipple operation].
AB  - A 65-year-old woman was admitted to our hospital with progressive confusion and
      hypersomnia. During admission she became comatose which was found to be caused by
      hepatic encephalopathy. Fifteen years earlier she had undergone a Whipple's
      pancreaticoduodenectomy for an adenocarcinoma of the pancreatic head. She had
      developed secondary endo- and exocrine pancreas insufficiency and a fatty liver.
      Non-alcoholic fatty liver disease (NAFLD) is a little-known late complication of
      a pancreaticoduodenectomy, possibly caused by postoperative exocrine pancreas
      insufficiency. NAFLD may lead to non-alcoholic steatohepatitis (NASH) which can
      ultimately result in liver cirrhosis. There have been no previous reports in the
      literature of hepatic encephalopathy presenting as liver failure secondary to
      NASH following pancreaticoduodenectomy.

PMID- 19857274
TI  - BayesPI - a new model to study protein-DNA interactions: a case study of
      condition-specific protein binding parameters for Yeast transcription factors.
AB  - BACKGROUND: We have incorporated Bayesian model regularization with biophysical
      modeling of protein-DNA interactions, and of genome-wide nucleosome positioning
      to study protein-DNA interactions, using a high-throughput dataset. The newly
      developed method (BayesPI) includes the estimation of a transcription factor (TF)
      binding energy matrices, the computation of binding affinity of a TF target site
      and the corresponding chemical potential. RESULTS: The method was successfully
      tested on synthetic ChIP-chip datasets, real yeast ChIP-chip experiments.
      Subsequently, it was used to estimate condition-specific and species-specific
      protein-DNA interaction for several yeast TFs. CONCLUSION: The results revealed
      that the modification of the protein binding parameters and the variation of the
      individual nucleotide affinity in either recognition or flanking sequences
      occurred under different stresses and in different species. The findings suggest
      that such modifications may be adaptive and play roles in the formation of the
      environment-specific binding patterns of yeast TFs and in the divergence of TF
      binding sites across the related yeast species.

PMID- 19857277
TI  - [Give attention to war in medical education].
AB  - Medical consequences of war are prominent in the media. The United Nations and
      the World Medical Association have called for medical curricula to permanently
      include consideration of human rights, in particular human rights in war time.
      Information on the medical consequences of war and weapon systems is valuable
      knowledge. Courses on this subject are popular amongst medical students, a
      considerable number of whom are willing to spend a period working for
      organisations as the Red Cross, Doctors without Borders or the Military Health
      Service. In spite of this, none of the Dutch medical faculties has given the
      subject a permanent place in its curriculum. Gathering knowledge on the medical
      consequences of war depends completely on the efforts of individuals.

PMID- 19857278
TI  - [A man with a dell over the symphysis pubica].
AB  - A 46-year-old man was referred to our emergency room after minimal trauma. He was
      diagnosed with symphysiolysis, which was based on a congenital variant instead of
      a traumatic injury.

PMID- 19857279
TI  - [An extremely painful ulcer on the lower leg; Martorell arteriolosclerotic
      ulcer].
AB  - A 63-year-old woman was referred to the dermatology outpatient department with
      extremely painful ulcers on the right lower leg. Medical history listed
      hypertension, diabetes mellitus and chronic obstructive pulmonary disease.
      Intensive analgesia was insufficient. Blood analysis, microbial cultures and
      venous ultrasound did not reveal a cause. At histopathologic examination of an
      ulcer, arteriolosclerosis was revealed. The patient was treated for Martorell
      arteriolosclerotic ulcer with nifedipine, acenocoumarol and split-thickness skin
      grafts followed by vacuum-assisted closure therapy. Two weeks postoperative,
      analgesia was discontinued and all ulcers were healed. Nifedipine and
      acenocoumarol were continued in the outpatient setting to prevent relapses.
      Patients with long-standing hypertension are particularly prone to cutaneous
      arteriolosclerosis. Thrombosis of the cutaneous arterioles results in painful
      ischemic ulcers. This disease probably frequently goes unrecognised.

PMID- 19857280
TI  - [Vitrectomy: in search of the ideal vitreous replacement].
AB  - Pars plana vitrectomy is a form of surgery to remove the vitreous body. It is
      performed with various eye diseases. Replacement of the vitreous body is
      necessitated by its removal. After more than 50 years the search for the ideal
      vitreous replacement has not yet ended. Different materials are used to replace
      the vitreous body. The advantages, disadvantages and applications of those
      materials are discussed. The lack of a material to successfully replace the
      vitreous body is a significant restriction in the treatment vitreoretinal
      pathologies.

PMID- 19857281
TI  - [Spontaneous pneumothorax as the first manifestation of a hereditary condition
      with an increased renal cancer risk].
AB  - Spontaneous pneumothorax can be due to Birt-Hogg-Dube syndrome (BHD syndrome), an
      autosomal dominant predisposition for fibrofolliculomas, multiple lung cysts,
      pneumothorax and renal cancer. The syndrome is the result of germline mutations
      in the FLCN (folliculin) gene. Its clinical presentation is highly variable.
      Consequently, this syndrome is probably under-diagnosed. An illustrative kindred
      is presented in which the index patient, a man aged 26, had recurrent episodes of
      pneumothorax without apparent skin lesions or renal abnormalities. He had
      bilateral mostly basally-located lung cysts. There was a family history of
      fibrofolliculomas, lung cysts, pneumothorax and clear cell renal cancer.
      Recognition of BHD is important since carriers of the mutation can be offered
      surveillance for early detection and treatment of renal cancer.

PMID- 19857282
TI  - [Safe introduction of laparoscopic hysterectomy using a mentor].
AB  - OBJECTIVE: Evaluation of the introduction of laparoscopic hysterectomy in a
      teaching hospital by means of a structured mentor-traineeship. DESIGN:
      Retrospective, with prospectively designed database. METHODS: By means of a
      mentor-traineeship the technique of laparoscopic hysterectomy was introduced to
      two gynaecologists in a teaching hospital. The primary outcome measures of the
      laparoscopic hysterectomies were duration of the operation, blood loss and
      complications. In addition, patient characteristics as well as main indication
      for surgery were analysed. The training period was defined per trainee as the
      relationship between operation duration and consecutive operations. Similar
      outcome measures of all laparoscopic hysterectomies performed during the same
      period by the mentor in his own hospital were used as a reference. RESULTS:
      During both mentor-traineeships, the main indication for surgery, the operation
      characteristics and the percentage of complications were comparable between
      trainee and mentor (p = 0.633). The operating time did not differ clinically
      significantly between trainee and mentor. Both trainees realised a learning
      curve, while the operating time remained statistically constant and comparable to
      that of the mentor. During the mentor-traineeships and the two following years
      the number of laparoscopic hysterectomies increased (p = 0.001), while the number
      of abdominal hysterectomies diminished (p = 0.002). CONCLUSION: A mentor was able
      to effectively introduce laparoscopic hysterectomy in a clinic without
      jeopardizing patient safety, as main indication, operating time and percentage of
      complications were comparable to those of the mentor in his/her own hospital. Due
      to this safe method of introduction of the new procedure more patients are able
      to benefit from the advantages of this surgical technique.

PMID- 19857283
TI  - [Dutch patients with hereditary pancreatitis; high mutation frequency, relatively
      little pain].
AB  - OBJECTIVE: To assess genetic, clinical and morphological characteristics of
      hereditary pancreatitis, a rare type of chronic pancreatitis with an early onset
      of symptoms, which is, among others, caused by mutations in the PRSS1 gene.
      DESIGN: Observational cohort study. METHOD: The study population consisted of 496
      patients (27,375 person-years) who were referred to Radboud University Nijmegen
      Medical Centre for molecular diagnosis of hereditary pancreatitis during period
      2000 to 2007. 61 patients with a positive family history of hereditary
      pancreatitis were selected. Analysis for PRSS1 gene mutations was performed by
      complete sequence analysis of the exons. All patients received a structured
      questionnaire. RESULTS: From 25 families 61 patients were included (2,047 person
      years). PRSS1 mutations were detected in 52 patients (85.2%): p.R122H (67.2%),
      p.N29I (14.8%), p.E79K (1.6%), p.N29T (1.6%). In the 40 patients whose clinical
      data were known the median age at diagnosis was 10.5 years (range: 0-42 years).
      Pain was reported in 28 (70% of 40 patients in whom all information was
      complete). 27 patients (67.5%) were admitted to the hospital once or more due to
      the attacks of pancreatitis. Exocrine and endocrine dysfunction was seen in 6
      patients (15%). 24 patients (60%) had undergone a surgical intervention, 10 of
      whom had undergone a pancreaticojejunostomy. A family history of pancreatic
      carcinoma was found in 5 patients (12.5%). CONCLUSION: The percentage of PRSS1
      mutation was high (85.2%) among this Dutch population that was selected on basis
      of a positive family history of hereditary pancreatitis. Most patients had no
      chronic pain.

PMID- 19857284
TI  - [Insufficient consideration for anxiety disorders in the elderly].
AB  - The elderly often present with anxiety disorders in primary care, and specific
      treatment options in that setting are needed. In a randomised clinical trial, 7
      sessions of cognitive behavioural therapy performed in the primary care setting
      by very experienced cognitive behavioural therapists was found to reduce worry,
      depressive symptoms and general health symptoms. However, severity of generalised
      anxiety disorder did not improve, and medication use did not diminish during the
      intervention. In the Dutch primary care setting, implementation of such a
      therapeutic option would require an organisational intervention. Moreover, such
      an intervention should be combined with an intervention aimed at reducing
      benzodiazepine use, i.e. in a collaborative care model specifically designed for
      anxiety disorder in the elderly.

PMID- 19857285
TI  - [A painful little finger after minor trauma].
AB  - A 23-year old woman visited the Emergency Room with a pathological fracture of
      her left fifth finger due to an enchondroma.

PMID- 19857286
TI  - [Resistance to coumarin derivatives due to mutated vitamin-K enzyme].
AB  - In 2006 a case report was published in this journal describing partial
      acenocoumarol- and phenprocoumon resistance in a 78-year-old man. A mutation in
      the VKORC1 gene was suggested to be the cause of the observed resistance. We
      examined the patient and found a new and hitherto unknown mutation in the VKORC1
      gene which may well explain the observed resistance. The mutation concerns a
      polymorphism in exon 2 that predicts the substitution of tryptophan at position
      59 of the VKOR protein by arginine, the p.Trp59Arg mutation. Meanwhile, we have
      detected the same p.Trp59Arg mutation in another patient with coumarin derivative
      resistance. The fact that this mutation did not occur in 100 individuals who
      responded well to coumarin derivatives, together with the knowledge that amino
      acid 59 is conserved among species, renders it likely that p.Trp59Arg was the
      cause of the partial acenocoumarol- and phenprocoumon resistance observed in
      these two patients.

PMID- 19857287
TI  - [Kidney donor with severe disseminated intravascular coagulation: transplantation
      however successful].
AB  - A 41-year-old male, with no previous medical history, was admitted to our
      intensive care unit with severe isolated neurotrauma and a Glasgow Coma Scale of
      E1-M1-V1, mid-dilated unreactive pupils and severe abnormalities on the brain CT
      scan. A severe syndrome of disseminated intravascular coagulation (DIC) and non
      oliguric renal insufficiency developed. Following clinical and neurophysiological
      examination the patient was declared brain-dead, and the family gave permission
      for organ donation. The left kidney was transplanted and functioned well
      immediately. However, in view of the DIC and renal function disorders the right
      kidney was not considered usable for transplantation elsewhere. Pathological
      examination revealed many fibrin thrombi in the glomerular capillaries and acute
      tubular necrosis. This case supports the view that thrombotic microangiopathy in
      kidneys of patients with DIS, even with renal function impairment, is not an a
      priori reason for excluding donation.

PMID- 19857288
TI  - [Headache after coughing: consider cough headache].
AB  - A 67-year-old male and a 43-year-old female were referred to hospital with
      headaches after intracranial pressure increasing activities, such as coughing.
      Both patients were diagnosed with primary cough headache. In the case of the
      first patient, this diagnosis was considered shortly after presentation. His
      headache disappeared with the standard treatment for primary cough headache,
      consisting of indomethacin and a proton pump inhibitor. The second patient
      received medicinal and surgical treatment for rhinosinusitis. These treatments
      did not improve the headache symptoms. Eventually she was also diagnosed with
      primary cough headache, and became pain-free with indomethacin and a proton pump
      inhibitor. Primary cough headache should be differentiated from secondary cough
      headache, in which the symptoms are caused by structural abnormalities of the
      brain. Additional investigation is required to differentiate between the two. The
      diagnosis of primary cough headache is supported by a positive reaction to trial
      treatment with indomethacin.

PMID- 19857289
TI  - [Treatment of secondary peritonitis: slow progress].
AB  - Secondary peritonitis is associated with a high mortality and morbidity. Besides
      adequate antimicrobial therapy and resuscitation, surgical intervention is the
      cornerstone of the treatment of these often severely ill patients. Antifungal
      prophylaxis is advised for patients who have a high risk of developing a fungal
      infection. Extensive lavage of the peritoneal cavity after elimination of the
      intra-abdominal infectious focus has no demonstrable positive effect and can even
      be harmful. A randomised clinical trial showed that relaparotomy on demand (ROD)
      after the first surgery is the preferred treatment strategy in the case of
      clinical deterioration, irrespective of the severity of disease. The effective
      and safe use of ROD requires intensive monitoring of the patient in a setting
      where diagnostic tests and decision making about relaparotomy are guaranteed
      around the clock. A reduction in the mortality and morbidity associated with
      secondary peritonitis can be achieved with a multidisciplinary approach involving
      more extensive diagnostic and decisional support.

PMID- 19857290
TI  - [Unexplained iron-deficiency due to Helicobacter pylori].
AB  - Iron-deficiency is one of the most prevalent worldwide deficiencies. In the
      western world, chronic, mostly occult, blood loss is a frequent cause. However,
      in up to 30% of patients an underlying cause is never found during routine
      investigations. We describe two male patients aged 20 and 62 years and a 77-year
      old woman with mainly fatigue and iron-deficiency showing no abnormalities on
      endoscopy. In these patients, infection with H. pylori was regarded as the major
      cause of iron deficiency, and there was lasting normalization of iron status and
      haemoglobin after successful eradication therapy. Although the underlying
      mechanism still remains to be established, we recommend investigation for H.
      pylori infection and appropriate treatment in case of unexplained iron
      deficiency. In a number of patients, eradication results in a clinically
      significant improvement of both iron-balance and status.

PMID- 19857291
TI  - [Endoscopic posterior adrenalectomy; results of 100 procedures in University
      Medical Center Utrecht].
AB  - OBJECTIVE: To describe the results of 100 endoscopic posterior retroperitoneal
      adrenalectomies performed in the University Medical Center Utrecht, the
      Netherlands. DESIGN: Descriptive, retrospective. METHOD: In the period August
      1997-March 2008 100 endoscopic posterior retroperitoneal adrenalectomies were
      performed in the University Medical Center Utrecht. Data were collected
      retrospectively on patients, operations, complications and course following the
      procedure. RESULTS: In this period 88 unilateral and 6 bilateral EPRA procedures
      were performed in 94 patients. The most common indications for unilateral EPRA
      were pheochromocytoma (33), Cushing's syndrome (16) and Conn's syndrome (20).
      Preoperative diagnosis involved clinical examination, hormonal analysis and
      radiological imaging. Mean operative time was 110 min and showed a clear learning
      curve. The mean intraoperative blood loss was 30 ml. The median size of the
      lesions was 2.8 cm (range: 0.4-7.5). Conversion to open surgery was necessary in
      2 patients. No major intraoperative complications occurred. Postoperative
      complications occurred in 7 patients, of which 2 were severe and 5 were mild.
      Surgical reintervention was required in 1 patient. Median postoperative stay was
      3 days. CONCLUSION: In experienced hands endoscopic posterior retroperitoneal
      adrenalectomy appears to be a safe and effective treatment for adrenal gland
      lesions.

PMID- 19857293
TI  - [Internship abroad: not suitable for all medical students].
AB  - Medical students in the Netherlands have the opportunity to follow an internship
      abroad. However, this is often at the expense of developing their competence, for
      example in situations where they do not learn abroad what they would have learnt
      had they followed the Dutch programme. An international internship should,
      therefore, not be obliged for all medical students.

PMID- 19857294
TI  - [Internship abroad: should be mandatory for all medical students].
AB  - Medical students in the Netherlands have the opportunity to follow an internship
      abroad. In general, they view this as a unique experience. There are personal,
      scientific, political and humanitarian reasons to support making such an
      internship abroad obligatory for all medical students. Therefore the Dutch
      medical study programme, developed in 2001, needs to be reviewed.

PMID- 19857295
TI  - [A man with a widened mediastinum after trauma].
AB  - A 36-year-old male patient with a high energy trauma had a widened mediastinum
      caused by a traumatic transsection of the aorta.

PMID- 19857296
TI  - [Loss of renal function due to deep infiltrating endometriosis; a complicated
      consideration in women who wish to have children].
AB  - Three nulliparous women, aged 39, 34 and 26 years, who were treated for fertility
      problems and who were affected by endometriosis, presented with ureteral
      obstruction caused by deep infiltrating endometriosis. The first two patients had
      complete unilateral loss of kidney function at the time of diagnosis. They chose
      to have fertility treatment first and both became pregnant. The third patient
      still had 24% renal function in the affected left kidney. She was treated by
      complete surgical resection of the endometriosis and reimplantation of the
      ureter. Ureteral obstruction is a rare, but serious, complication of deep
      infiltrating endometriosis. Timely recognition is important, since delay results
      in unnoticed loss of renal function. Clinical investigation for endometriosis of
      the posterior vaginal fornix is recommended for all patients with chronic
      abdominal pain, severe dysmenorrhoea or deep dyspareunia. On diagnosis of deep
      infiltrating endometriosis, further examination is necessary to detect possible
      ureteral obstruction and consequent hydronephrosis, which can be demonstrated by
      ultrasound. MRI is of value to map the extent of disease, which is usually multi
      focal. Surgery to relieve ureteral obstruction and remove all endometriotic
      lesions is the treatment of choice if the kidney is still functional.

PMID- 19857297
TI  - [Internally situated sacrococcygeal teratomas, often invisible but not harmless].
AB  - A sacrococcygeal teratoma (SCT) may be completely concealed within the pelvis and
      therefore not be visible externally. Symptoms of such an SCT can be very
      aspecific. We present 4 patients with an intrapelvic SCT. The first patient, a
      newborn girl, had an antenatally-diagnosed cystic mass in her pelvis, which was a
      benign SCT. After removal she suffered from neurogenic bladder dysfunction. The
      second patient was a 2-year-old boy who after two incomplete resections of a
      benign intrapelvic SCT, developed a malignant SCT. The other 2 patients, 2 girls
      aged 4 and 15 years, both presented with constipation and abdominal pain and were
      diagnosed as having an SCT. Early detection and radical excision, including
      removal of the os coccygis, are necessary to prevent development of malignancy.
      Long-term functional sequelae can occur after excision.

PMID- 19857298
TI  - [Treatment of Dupuytren's contracture; an overview of options].
AB  - In this article we systematically review treatment options for Dupuytren's
      contracture. There is little evidence on the effectiveness of many treatment
      modalities for Dupuytren's disease other than expert's opinions (level 4). Most
      hand surgeons perform selective fasciectomy for Dupuytren's disease. Because of
      its lower recurrence rate, dermofasciectomy is increasingly being performed to
      treat recurrences. Percutaneous needle fasciotomy is a minimally invasive
      treatment with good short-term results in patients with mild to moderate
      contractures, but it has a high recurrence rate. Radiotherapy and the use of
      collagenase are promising, but their role in treating Dupuytren's disease is
      still unclear.

PMID- 19857299
TI  - [Babies with cranial deformity].
AB  - Plagiocephaly was diagnosed in a baby aged 4 months and brachycephaly in a baby
      aged 5 months. Positional or deformational plagio- or brachycephaly is
      characterized by changes in shape and symmetry of the cranial vault. Treatment
      options are conservative and may include physiotherapy and helmet therapy. During
      the last two decades the incidence of positional plagiocephaly has increased in
      the Netherlands. This increase is due to the recommendation that babies be laid
      on their backs in order to reduce the risk of sudden infant death syndrome. We
      suggest the following: in cases of positional preference of the infant, referral
      to a physiotherapist is indicated. In cases of unacceptable deformity of the
      cranium at the age 5 months, moulding helmet therapy is a possible treatment
      option.

PMID- 19857300
TI  - [Vaginal and cervical cancer due to diethylstilbestrol (DES); end epidemic].
AB  - OBJECTIVE: To determine the current situation regarding the epidemic of clear
      cell adenocarcinoma of the vagina and the uterine cervix (CCAC) in relation to
      the exposure in utero to diethylstilbestrol (DES). DESIGN: Descriptive. METHODS:
      Patients with CCAC of the uterine cervix or vagina born after 1946 and diagnosed
      in the period 1969-2005, were identified through the Nationwide network and
      registry of histo- and cytopathology in the Netherlands and from 2003 onwards
      through the Netherlands Cancer Registry. Exposure data and clinical data were
      obtained by means of questionnaires and medical records. The histology slides of
      tumours were reviewed. For the patients who did not provide consent, only the
      date of diagnosis and age at diagnosis were known (n = 10). RESULTS: Up to 2005,
      144 CCAC patients were registered. Age at diagnosis varied from 8-54 years (mean:
      28 years). In the years 1981-2000, the number of new diagnoses in 4 successive 5
      year periods was fairly stable (n=26-30) but it was considerably lower in 2001
      2005 (n=13). Of the patients whose history of intrauterine exposure to DES was
      known, 62% had been exposed (76/122). The mean age at diagnosis was 24 years for
      exposed patients compared to 32 years for non-exposed patients. The 10-year
      survival rate was 78% (95% CI: 68-87) for exposed and 69% (95% CI: 56-82) for non
      exposed patients. CONCLUSION: Since 2000, the incidence of CCAC of the vagina and
      cervix has decreased markedly compared to the situation in the 1980s and 1990 s.
      In particular, the number of patients with CCAC exposed in utero to DES has
      decreased. Whether this decrease shall continue over the coming years remains to
      be seen.

PMID- 19857301
TI  - [Screening for abdominal aortic aneurysm; effectivity and cost-effectiveness].
AB  - OBJECTIVE: To review the current literature concerning the effectivity and cost
      effectiveness of screening for abdominal aortic aneurysm (AAA). DESIGN:
      Systematic review. METHOD: A review of literature of evaluations of effectivity
      via meta-analyses and economic evaluations. RESULTS: The short-term meta-analyses
      showed that screening for AAA leads to a significant reduction of AAA-related
      mortality. The average absolute risk reduction (ARR) was 0.12%. The long-term
      meta-analysis also showed a significant reduction of overall mortality. The ARR
      was in this case almost 1%. The five economic evaluations all resulted in cost
      effectiveness ratios below euro 20,000 per quality-adjusted life year (QALY), a
      used threshold level in the Netherlands. CONCLUSION: Based on the available
      literature, screening for AAA has appeared to be both effective and cost
      effective. However, the economic evaluations did not always take into account the
      peri- and post-operative mortality and morbidity. Economic evaluations are only
      useful if all possible outcomes are included in the model. Therefore a good model
      analysis should be made for the Dutch situation, after which a decision may be
      taken on a possible pilot study and the optimal design thereof.

PMID- 19857302
TI  - [Total body CT scan as the primary diagnostic modality in multi-trauma patients].
AB  - Radiological imaging is highly protocolized during initial assessment of severely
      injured trauma patients. After an initial examination, radiography and ultrasound
      are performed. Imaging is frequently supplemented by CT scan of selective body
      areas. Technical features of CT scanners have improved drastically and the number
      of CT scanners located near or in trauma resuscitation rooms is increasing. These
      developments enable early CT scanning in trauma patients. Currently there is an
      ongoing discussion as to whether 'total body' CT scan (TBCT) should be used as a
      primary and sole diagnostic imaging tool during workup of trauma patients. Recent
      research on TBCT in multi-trauma patients shows promising results and several
      large European trauma centers have already protocolized this strategy. These
      studies lack a good study design, so more prospective research on clinical
      outcomes, cost effectiveness and radiation exposure is necessary. As part of a
      pilot study in preparation for a randomized multicenter study, the University
      Medical Centre in Amsterdam in the Netherlands is performing TBCT in severely
      injured trauma patients.

PMID- 19857303
TI  - [Diagnostic image. A woman with orange hand lines].
AB  - Incidental cholesterol measurement in a 44-year-old woman revealed 12 mmol/l. She
      also had orange hand lines and elbow papules, caused by familial
      dysbetalipoproteinaemia.

PMID- 19857304
TI  - [Patient with relapsed hyperparathyroidism and neck swelling].
AB  - 72-year-old woman with a history of primary hyperparathyroidism, for which she
      underwent surgery years previously, went to see her general practitioner because
      of a swelling in her neck that had been present for a few months and was growing
      in size. Other than this she had no symptoms. During the physical examination a
      solid elastic, non-fixed swelling with a diameter of about 3 cm was palpable on
      the right of the neck, medially to the sternocleidomastoid muscle. The swelling
      did not move when she swallowed. Laboratory tests and an MRI scan were suggestive
      of parathyroid carcinoma. An examination of the neck showed a large, irregular,
      lobed soft tumour and several small deposits with a yellowish brown appearance.
      Histology showed no characteristics of malignancy, but showed a picture
      consistent with the diagnosis of 'parathyromatosis', a rare disorder
      characterized by hormonally active ectopic parathyroid tissue. Treatment is
      primarily surgical, aimed at radical resection. Medicinal therapy using a
      calcimimetic agent may have a role as an adjuvant treatment.

PMID- 19857305
TI  - [Respiratory complications in early elective caesarean section].
AB  - Two neonates were born via elective caesarean section, after 38 2/7 and 38 0/7
      weeks of gestation, respectively. They developed serious respiratory
      complications: a pneumothorax and respiratory insufficiency, respectively, for
      which they were transferred to a neonatal intensive care unit and were
      mechanically ventilated. If a caesarean section is performed before 39 0/7 weeks
      of gestation, the risk of respiratory complications, such as idiopathic
      respiratory distress syndrome or wet lung disease, is increased. Despite this
      scientific evidence, elective caesarean sections continue to be planned before 39
      weeks of gestation.

PMID- 19857306
TI  - [Application of tumour markers in clinical practice].
AB  - Usefully requesting and applying serum tumour markers in diagnosis and treatment
      can be difficult. It should be noted that tumour markers are used for varying
      purposes: screening, diagnosis, staging and prognostic evaluation, detection of
      recurrence and treatment monitoring. Due to the poor sensitivity and specificity
      of current tumour markers, most are not suitable for screening an asymptomatic
      population. Further, the benefits of an improved prognosis by early detection
      should be weighed against a poorer quality of life and the cost of substantial
      over-diagnosis and over-treatment. Serum tumour markers are particularly
      applicable in treatment monitoring and detection of recurrence. Sometimes they
      can be used to support the diagnostic process and give useful prognostic
      information.

PMID- 19857307
TI  - [Frail elderly women following traffic accident: a specific approach to the
      trauma care chain].
AB  - Three octogenarian women suffered severe blunt trauma because of a car crash. The
      first patient was 81 years old. She had an instable dens fracture, multiple rib
      fractures, a haematopneumothorax and multiple extremity fractures. The second
      patient was 82 years old and was diagnosed with a flail chest because of multiple
      rib fractures, pelvic fractures, and thoracic spine fractures. Before the crash,
      she already needed help for her daily functioning. The third patient, 84 years
      old, developed a bradycardia at the site of the crash. In the hospital she was
      diagnosed with multiple rib fractures, a sternum fracture and a pneumothorax.
      After appropriate treatment, the second patient had no prospect of recovery and
      the care was primarily aimed at comfort, until she died. The other two patients
      remained in a rehabilitation clinic for months after the accident. The necessary
      approach to first trauma care, ICU care and rehabilitation differs between young
      and octogenarian patients. These octogenarian female patients constitute a
      special group of patients because of their frailty. Due to demographic
      developments and the changes in trauma care, such patients will be treated more
      often and further in the care chain. During the ICU stay they will require
      extensive support because of their frailty. The patient's own efforts will also
      be tremendous. The balance between quality of life adjusted years won and the
      toll paid by the patient has to be guarded with great care.

PMID- 19857308
TI  - [Diagnostic second opinion: what does it add? Patient satisfaction, but diagnosis
      is rarely altered].
AB  - OBJECTIVE: To establish the yield of diagnostic second opinions in patients
      referred to a general internal medicine outpatient clinic at an academic
      hospital. DESIGN: Retrospective cohort study. METHODS: Of the patients newly
      referred to the general internal medicine outpatient clinic at the VU Medical
      Center, Amsterdam, the Netherlands during 2007, 86 were referred for a diagnostic
      second opinion. The diagnostic yield was assessed by comparing the outcome of the
      first and second opinions. To assess patient satisfaction, a telephone survey was
      held. RESULTS: There was a difference in diagnostic outcome between the first and
      the second opinions in 10 of the 86 patients included (12%). A significantly
      higher proportion of these patients was referred by a specialist, as compared to
      self-referrals or referrals by a general practitioner. The average satisfaction
      rate was high in all groups with a statistically significant difference in favour
      of the group with a different diagnostic outcome after the second opinion. The
      communication skills of the physician were the strongest determinant for overall
      satisfaction (r = 0.845; p < 0.001). CONCLUSION: In an academic hospital second
      opinions for diagnostic purposes rarely yield a different diagnosis. Nonetheless,
      patients are usually satisfied with the process. During referral for a second
      opinion, care should be taken to avoid creating high expectations regarding a
      difference in diagnostic outcome.

PMID- 19857309
TI  - [Atopic eczema in children: a prospective study into prevalence and severity].
AB  - OBJECTIVE: To study the prevalence and severity of atopic eczema (AE) in children
      aged 0 to 4 years. DESIGN: Observational study. METHODS: We registered all
      children who visited the child health centres in the West-Veluwe region of the
      Netherlands between 1 January and 30 April 2005 and used objective criteria to
      establish if they suffered from AE. Data were also collected about subjective
      symptoms such as itch and sleeping problems and the severity of AE was
      established using the Three Item Severity (TIS) score. RESULTS: A total of 9351
      children were examined for eczema (5796 infants and 3555 toddlers) . Infants
      suffered more frequently from eczema than toddlers (8.70% versus 5.54%) and boys
      suffered more than girls. CONCLUSION: The total prevalence of AE in this study
      group of children aged 0 to 4 years was 7.5%.

PMID- 19857310
TI  - [Seclusion: a medical and political problem].
AB  - Seclusion, i.e. locking up psychiatric patients in safety rooms as a coercive
      measure, is common practice in the Netherlands. The Dutch mental health act
      permits seclusion of involuntarily admitted patients in acute emergency
      situations, or when it is absolutely necessary to avert danger caused by the
      patient's mental illness. Since 2006, a nationwide project aimed at the reduction
      of the number and duration of seclusion episodes by 10% a year has yielded
      positive results in one-third of mental hospitals. The Dutch Minister of Health
      recently advocated a further reduction of seclusion rates by 50% over the next
      year. We argue that short-term abolition of seclusion is an illusion and that the
      safety of patients and employees on closed psychiatric wards must be guaranteed.
      A further reduction in the practice of seclusion requires a major cultural change
      in psychiatry, adjustment of the law, and the financing of high-care psychiatric
      wards which are better staffed with appropriately qualified personnel.

PMID- 19857311
TI  - [Diagnostic image. A woman with an abnormal screening mammogram].
AB  - A 56-year-old woman had an abnormal mammogram and a palpable mass in the left
      breast. Cytological and histological examination revealed a pilomatrixoma of the
      breast.

PMID- 19857312
TI  - [Castleman's disease, a fatal cause of lymph node enlargement and fever].
AB  - A 71-year old Turkish man with fever, night sweats and generalized
      lymphadenopathy was diagnosed as having multicentric Castleman's disease. This is
      a rare and often fatal cause of lymph node enlargement and fever. Histological
      investigation confirms the diagnosis, but the morphological features closely
      resemble reactive lymphadenopathy or lymphoma. Infection with human herpes virus
      8 is associated with Castleman's disease, in both hiv-positive and hiv-negative
      patients. An interleukin-6 mediated immune response against HHV-8 seems to play
      an important role in the pathogenesis of the multicentric form of Castleman's
      disease. The disease is usually rapidly progressive, but can have a milder
      course. There is no standard treatment: usually systemic chemotherapy in
      combination with steroids is applied..Recently, promising results have been
      obtained using rituximab and anti-IL-6-receptor antibodies.

PMID- 19857313
TI  - [Treatment for diverticulitis not thoroughly researched].
AB  - In the Netherlands approximately 14,000 patients are referred to hospital for
      diverticular disease each year. Overall controversy persists about four aspects
      of treatment of the different stages of diverticulitis, i.e. the role of
      antibiotics in the treatment of mild diverticulitis, the question of whether
      elective surgical resection is justified in recurrent diverticulitis or in
      persisting abdominal symptoms after an episode of diverticulitis, the question of
      whether patients with purulent peritonitis due to perforation may be treated with
      laparoscopic peritoneal lavage instead of Hartmann's procedure, and finally,
      whether resection with a primary anastomosis is a feasible and safe alternative
      to Hartmann's procedure in the surgical treatment of Hinchey III or IV
      diverticulitis. These questions will be addressed in four upcoming Dutch
      randomised trials.

PMID- 19857314
TI  - [Influenza vaccination of immunocompromised patients: safe and effective].
AB  - Influenza vaccination is important in order to limit flu-related morbidity and
      mortality. This especially applies to immunocompromised patients, such as HIV
      infected individuals and patients on immunosuppressive treatment, who have an
      increased risk for developing complications from influenza. Influenza vaccine can
      be safely administered to all immunocompromised patients, but the effectiveness
      of the vaccine may be reduced. Uncertainty still exists concerning the value of
      an increased vaccine dose or booster vaccination: if positive effects exist, they
      are probably only of marginal clinical importance. Despite clearly reduced
      effectiveness, vaccination of immunocompromised patients is still valuable in
      view of the high absolute risk of infection and complications.

PMID- 19857315
TI  - [Serious sequelae of hypothermia in cryoglobulinaemia].
AB  - Cryoglobulinaemia was diagnosed in three patients. The first was a 61-year-old
      man with severe skin involvement and polyneuropathy caused by type I
      cryoglobulinaemia associated with a small B cell clone in the bone marrow. A 73
      year-old woman presented with neuropathy and renal and skin involvement due to
      type II cryoglobulinaemia associated with hepatitis C virus infection. The third
      patient was a 23-year-old woman with skin and renal involvement caused by type
      III cryoglobulinaemia. Cryoglobulins are circulating proteins that precipitate
      below a temperature of 37 degrees Celsius. This precipitation causes several
      signs and symptoms and, in some cases, severe organ damage. According to the
      Brouet classification, there are three different types of cryoglobulinaemia.
      Treatment focuses on their underlying causes and on the prevention of
      cryoglobulin precipitation. It is important to avoid hypothermia, which was the
      cause of severe manifestations in two of our patients.

PMID- 19857317
TI  - [New influenza A (H1N1): advised indication and prescription of antiviral drugs].
AB  - AIM: To evaluate to what extent antiviral drugs have been prescribed to patients
      other than confirmed cases and their contacts since the emergence of New
      Influenza A (H1N1). DESIGN: Descriptive. METHODS: We inspected monthly and annual
      counts of oseltamivir (Tamiflu) and zanamivir (Relenza) prescriptions dispensed
      by public pharmacies in the Netherlands from 2005 until 30 June 2009. We compared
      these figures with counts of antiviral cures supplied by the Netherlands Vaccine
      Institute (NVI) to Municipal Health Services (GGDs) for the treatment of
      confirmed cases and contacts up until 1 July 2009. RESULTS: Counts of oseltamivir
      prescriptions dispensed by public pharmacies started to increase in April 2009.
      Although this increase might seem limited compared to increases in 2005/2006
      triggered by avian influenza in Turkey, up to 1 July 2009 oseltamivir was
      dispensed 9069 times, which is 9 times more often than in 2007 and 15 times more
      often than in 2008. This total was also approximately 10 times more than that
      dispensed by Municipal Health Services to confirmed cases of H1N1 infection and
      their contacts. General practitioners prescribed 78% of the prescriptions
      dispensed. Counts of zanamivir prescriptions dispensed hardly increased.
      CONCLUSION: The counts of oseltamivir prescriptions dispensed by Dutch public
      pharmacies has increased, even though patients with a confirmed H1N1 infection
      and their contacts had already been treated by the Municipal Health Services.
      Therefore it cannot be excluded that this increase is due to prescription on a
      precautionary basis. To avoid unnecessary risks for the spread of resistant
      strains and a shortage of antivirals later in the epidemic, physicians should
      refrain from prescribing antiviral drugs if patients do not match the nationally
      advised medical grounds for treatment.

PMID- 19857316
TI  - [The citizen as plaintiff in disciplinary procedures, lack of complaints possibly
      due to poor knowledge of the disciplinary system for health care].
AB  - OBJECTIVE: To provide insight into the general public's knowledge of disciplinary
      procedures, their grounds for lodging a complaint or otherwise and their
      confidence in the disciplinary system. DESIGN: Descriptive. METHOD: In 2008,
      questionnaires were sent to all 1368 members of the Healthcare Consumer Panel of
      the Netherlands Institute for Health Services Research (NIVEL), to check their
      knowledge about the disciplinary procedures. The response was 69%. RESULTS: The
      majority of the respondents were not well-informed about the aims and procedures
      of the disciplinary system. They did not know which complaints can be brought
      before a disciplinary board and were of the opinion that you had to be very
      confident about your case to lodge a complaint. Many respondents expressed
      concerns about the accessibility of the disciplinary system. More than one-third
      of the respondents had no confidence in the independent status of the
      disciplinary proceedings. CONCLUSION: Efforts should be made to optimise the
      possibilities for members of the general public to lodge complaints. Examples
      are: organising a single office where complaints can be submitted, providing
      public information materials about the aims and procedures of the disciplinary
      system, and supplying concrete support to individuals who wish to lodge a
      complaint. For complaints that arise as a result of shortcomings in the quality
      of care provided, but which are not serious enough to justify the imposition of
      sanctions, ways should be found to provide plaintiffs with a just outcome. For
      example, the professionals involved should make it clear how the incident will be
      prevented from happening again.

PMID- 19857319
TI  - [No evidence of fewer influenza complications with oseltamivir].
AB  - Since August 7th, treatment with neuraminidase inhibitors (oseltamivir) in the
      Netherlands has been limited to those patient groups who are considered at high
      risk of influenza-related complications. This policy is based on one study which
      shows only limited evidence of the effectiveness of neuraminidase inhibitors in
      lowering the number of such complications.

PMID- 19857320
TI  - The myth of language universals: language diversity and its importance for
      cognitive science.
AB  - Talk of linguistic universals has given cognitive scientists the impression that
      languages are all built to a common pattern. In fact, there are vanishingly few
      universals of language in the direct sense that all languages exhibit them.
      Instead, diversity can be found at almost every level of linguistic organization.
      This fundamentally changes the object of enquiry from a cognitive science
      perspective. This target article summarizes decades of cross-linguistic work by
      typologists and descriptive linguists, showing just how few and unprofound the
      universal characteristics of language are, once we honestly confront the
      diversity offered to us by the world's 6,000 to 8,000 languages. After surveying
      the various uses of "universal," we illustrate the ways languages vary radically
      in sound, meaning, and syntactic organization, and then we examine in more detail
      the core grammatical machinery of recursion, constituency, and grammatical
      relations. Although there are significant recurrent patterns in organization,
      these are better explained as stable engineering solutions satisfying multiple
      design constraints, reflecting both cultural-historical factors and the
      constraints of human cognition. Linguistic diversity then becomes the crucial
      datum for cognitive science: we are the only species with a communication system
      that is fundamentally variable at all levels. Recognizing the true extent of
      structural diversity in human language opens up exciting new research directions
      for cognitive scientists, offering thousands of different natural experiments
      given by different languages, with new opportunities for dialogue with biological
      paradigms concerned with change and diversity, and confronting us with the
      extraordinary plasticity of the highest human skills.

PMID- 19857345
TI  - Introduction to the supplement: innovation associated with the treatment of
      patients with congenital and pediatric cardiac disease.

PMID- 19857346
TI  - Innovation and the role of the cardiac morphologist.

PMID- 19857347
TI  - The history of the development of paediatric echocardiography.

PMID- 19857348
TI  - Innovation in three-dimensional echocardiography and cardiac computed tomographic
      angiography.

PMID- 19857349
TI  - Innovation in interventional cardiology.

PMID- 19857350
TI  - Innovations in electrophysiology.

PMID- 19857351
TI  - The role of genetic testing in paediatric syndromes of sudden death: state of the
      art and future considerations.

PMID- 19857352
TI  - State-of-the-art management of hypertrophic cardiomyopathy in children.

PMID- 19857353
TI  - Innovation in basic science: stem cells and their role in the treatment of
      paediatric cardiac failure--opportunities and challenges.
AB  - Heart failure is a leading cause of death worldwide. Current therapies only delay
      progression of the cardiac disease or replace the diseased heart with cardiac
      transplantation. Stem cells represent a recently discovered novel approach to the
      treatment of cardiac failure that may facilitate the replacement of diseased
      cardiac tissue and subsequently lead to improved cardiac function and cardiac
      regeneration. A stem cell is defined as a cell with the properties of being
      clonogenic, self-renewing, and multipotent. In response to intercellular
      signalling or environmental stimuli, stem cells differentiate into cells derived
      from any of the three primary germ layers: ectoderm, endoderm, and mesoderm, a
      powerful advantage for regenerative therapies. Meanwhile, a cardiac progenitor
      cell is a multipotent cell that can differentiate into cells of any of the
      cardiac lineages, including endothelial cells and cardiomyocytes. Stem cells can
      be classified into three categories: (1) adult stem cells, (2) embryonic stem
      cells, and (3) induced pluripotential cells. Adult stem cells have been
      identified in numerous organs and tissues in adults, including bone-marrow,
      skeletal muscle, adipose tissue, and, as was recently discovered, the heart.
      Embryonic stem cells are derived from the inner cell mass of the blastocyst stage
      of the developing embryo. Finally through transcriptional reprogramming, somatic
      cells, such as fibroblasts, can be converted into induced pluripotential cells
      that resemble embryonic stem cells. Four classes of stem cells that may lead to
      cardiac regeneration are: (1) Embryonic stem cells, (2) Bone Marrow derived stem
      cells, (3) Skeletal myoblasts, and (4) Cardiac stem cells and cardiac progenitor
      cells. Embryonic stem cells are problematic because of several reasons: (1) the
      formation of teratomas, (2) potential immunologic cellular rejection, (3) low
      efficiency of their differentiation into cardiomyocytes, typically 1% in culture,
      and (4) ethical and political issues. As of now, bone marrow derived stem cells
      have not been proven to differentiate reproducibly and reliably into
      cardiomyocytes. Skeletal myoblasts have created in vivo myotubes but have not
      electrically integrated with the myocardium. Cardiac stem cells and cardiac
      progenitor cells represent one of the most promising types of cellular therapy
      for children with cardiac failure.

PMID- 19857354
TI  - Innovation in congenital and paediatric cardiac critical care.

PMID- 19857355
TI  - Innovative strategies for feeding and nutrition in infants with congenitally
      malformed hearts.

PMID- 19857356
TI  - The Gerbode defect: the significance of a left ventricular to right atrial shunt.
AB  - BACKGROUND: The so-called Gerbode ventriculo-atrial defect is a rare defect that
      permits shunting from the left ventricle to the right atrium. It takes 2 forms,
      either a deficiency of the atrioventricular membranous septum, or shunting
      initially through a ventricular septal defect, with atrial shunting occurring
      through a deficiency in the septal leaflet of the tricuspid valve. In this
      review, we describe the natural history and outcomes of surgical repair for the
      variant with shunting through a deficiency at the site of the atrioventricular
      membranous septum. METHODS: From 1990 to 2008, we identified 6 patients from our
      departmental database who had undergone surgical closure of a congenital defect
      of the atrioventricular component of the membranous septum. Median age at repair
      was 1.6 years, with a range, from 0.4 to 19 years. All patients were symptomatic,
      with 3 having congestive cardiac failure, 2 failing to thrive, and 2 having
      intolerance to exercise. All had a dilated right atrium demonstrated by
      echocardiogram, with a mean preoperative gradient measured by echocardiogram to
      be 109 millimetres of mercury, with a range from 65 to 150 millimetres of
      mercury. RESULTS: There was no operative or late mortality. The mean size of the
      defect was 6.2 +/- 2.0 millimetres, with a range from 4 to 8 millimetres. All
      were closed by insertion of a patch. The mean period of cardiopulmonary bypass
      was 90.5 +/- 11.3 minutes, the mean time of aortic cross-clamping 54.8 +/- 6.9
      minutes, and the mean length of stay in hospital 4.3 +/- 1.0 days. No patient had
      a residual defect, and only trivial regurgitation of the tricuspid valve was
      evident by postoperative echocardiography. There were no complications or
      reoperations. CONCLUSION: The membranous ventriculo-atrial defect can be
      recognized echocardiographically on the basis of dilation of the right atrium in
      the setting of an unusually high Doppler echocardiogram gradient compared to the
      ventricular septal defect with shunting only at ventricular level. Since all
      patients in our series were symptomatic, we recommend surgical closure of all
      these defects.

PMID- 19857357
TI  - Ethics of innovation in surgery for congenital cardiac diseases.

PMID- 19857358
TI  - Congenital cardiovascular nursing: preparing for the next decade.

PMID- 19857359
TI  - The 10th Annual C. Walton Lillehei Lecture: Good things in small packages:
      meeting challenges in the low-volume program.

PMID- 19857360
TI  - The Ninth Annual George R. Daicoff Lecture: The morality of innovation: a
      twentieth century surgical legacy.

PMID- 19857361
TI  - Development of the neotropical catfish Rhamdia quelen (Siluriformes,
      Heptapteridae) incubated in different temperature regimes.
AB  - The developmental stages for the embryonic and larval periods of the silver
      catfish (Rhamdia quelen) kept at different temperatures (21, 24, 27 and 30
      degrees C) are described. Fish were analysed under light and scanning electron
      microscopy. For embryonic development, we described 25 stages, which were grouped
      into seven periods named zygote, cleavage, blastula, gastrula, segmentation,
      pharyngula and hatching periods. For larval development, we defined three stages
      (early, mid, and late larvae). Additionally, the main ontogenetic events during
      the post-larvae and early juvenile periods were also described. This species
      presents a well developed lateral line and chemosensory systems that grow up
      during the larval period, maturing in the post-larvae. All tested temperatures
      are viable to R. quelen development, but a shorter incubation period was
      necessary to complete the development at lower temperatures. However, some
      malformations (heart edema) were verified at 30 degrees C.

PMID- 19857362
TI  - Several aspects of animal embryo cryopreservation: anti-freeze protein (AFP) as a
      potential cryoprotectant.
AB  - With the development of embryo technologies, such as in vitro fertilization,
      cloning and transgenesis, cryopreservation of mammalian gametes and embryos has
      acquired a particular interest. Despite a certain success, various
      cryopreservation techniques often cause significant morphological and biochemical
      alterations, which lead to the disruption of cell organelles, cytoskeleton
      damages, cell death and loss of embryo viability. Ultrastructural studies confirm
      high sensitivity of the cell membrane and organelle membrane to freezing and
      thawing. It was found that many substances with low molecular weights have a
      protective action against cold-induced damage. In this concern, an anti-freeze
      protein (AFP) and anti-freeze glycoproteins (AFGPs), which occur at extremely
      high concentrations in fish that live in Arctic waters and protect them against
      freezing, may be of potential interest for cryostorage of animal embryos at ultra
      low temperatures. This mini-review briefly describes several models of AFP/AFGP
      action to preserve cells against chilling-induced damages and indicates several
      ways to improve post-thaw developmental potential of the embryo.

PMID- 19857363
TI  - Transportability and feasibility of Social Cognition And Interaction Training
      (SCIT) in community settings.
AB  - BACKGROUND: Social Cognition and Interaction Training (SCIT) is a manual-based
      group intervention designed to improve social cognition in schizophrenia. Initial
      studies conducted by the developers of SCIT suggest that the intervention has
      promise in ameliorating social cognitive dysfunction in both inpatients and
      outpatients. AIMS: The current study is a preliminary evaluation of SCIT in
      community samples. METHOD: An uncontrolled, pre-post design was used in this
      initial feasibility study. A collaborative research-clinical approach was
      employed to enable research evaluation while also meeting the administrative
      goals of participating clinics, and working within the constraints of real-world
      clinical practice. Transportability, acceptability, and feasibility of SCIT were
      evaluated in terms of pre- and post-treatment evaluations, client attendance data
      (N = 50), and clinic administrators' decisions about whether to integrate SCIT
      into regular programming. Social-cognitive outcome measures assessed emotion
      perception, Theory of Mind, and attributional bias. RESULTS: These support the
      transportability, acceptability, and feasibility of SCIT in community settings.
      SCIT has been integrated into routine practice at several test sites. Tentative
      support was found for improvement in emotion perception and Theory of Mind, but
      not attributional bias. CONCLUSIONS: SCIT may be a promising intervention for
      community agencies serving individuals with psychotic disorders who seek to
      improve their social functioning.

PMID- 19857364
TI  - Principal components analysis of the hypomanic attitudes and positive predictions
      inventory and associations with measures of personality, cognitive style and
      analogue symptoms in a student sample.
AB  - BACKGROUND: An integrative cognitive model proposed that ascribing extreme
      personal appraisals to changes in internal state is key to the development of the
      symptoms of bipolar disorder. The Hypomanic Attitudes and Positive Predictions
      Inventory (HAPPI) was developed to measure these appraisals. AIMS: The aim of the
      current study was to validate an expanded 61-item version of the HAPPI. METHOD:
      In a largely female student sample (N = 134), principal components analysis (PCA)
      was performed on the HAPPI. Associations between the HAPPI and analogue bipolar
      symptoms after 3 months were examined. RESULTS: PCA of the HAPPI revealed six
      categories of belief: Self Activation, Self-and-Other Critical, Catastrophic,
      Extreme Appraisals of Social Approval, Appraisals of Extreme Agitation, and Loss
      of Control. The HAPPI predicted all analogue measures of hypomanic symptoms after
      3 months when controlling for baseline symptoms. In a more stringent test
      incorporating other psychological measures, the HAPPI was independently
      associated only with activation (e.g. thoughts racing) at 3 months. Dependent
      dysfunctional attitudes predicted greater conflict (e.g. irritability),
      depression and reduced well-being, hypomanic personality predicted self-reported
      diagnostic bipolar symptoms, and behavioural dysregulation predicted depression.
      CONCLUSIONS: Extreme beliefs about internal states show a modest independent
      association with prospective analogue bipolar symptoms, alongside other
      psychological factors. Further work will be required to improve the factor
      structure of the HAPPI and study its validity in clinical samples.

PMID- 19857365
TI  - Maternal consumption of fructo-oligosaccharide diminishes the severity of skin
      inflammation in offspring of NC/Nga mice.
AB  - Strategies to manipulate the gut microbiota in infancy have been considered to
      prevent the development of allergic diseases later in life. We aimed to elucidate
      the effects of maternal dietary supplementation with a prebiotic oligosaccharide
      on gut microbiota and spontaneously developing atopic dermatitis-like skin
      lesions in the offspring of NC/Nga mice. Female NC/Nga mice were fed diets either
      with or without fructo-oligosaccharide supplementation during pregnancy and
      lactation. After weaning, offspring were fed the diets supplemented with or
      without fructo-oligosaccharide for 11 weeks in an air-uncontrolled conventional
      room. Changes in gut microbiota were assessed by denaturing gradient gel
      electrophoresis of the PCR-amplified 16S rRNA gene. Skin lesions were evaluated
      by a clinical score and scratching behaviour. Serum antibody levels were measured
      by ELISA, and expression levels of cytokines and chemokines in lesional tissue
      were evaluated by quantitative RT-PCR. Maternal supplementation with fructo
      oligosaccharide modulated the gut microbiota in sucklings. Although maternal
      supplementation with fructo-oligosaccharide suppressed the increase in clinical
      skin severity score and scratching behaviour in offspring, dietary fructo
      oligosaccharide after weaning was less effective. The diminution of skin lesions
      was accompanied by lower serum concentrations of total IgG1 and lower expression
      levels of TNF-alpha in the lesional tissue. These data suggest that maternal
      consumption of fructo-oligosaccharide diminishes the severity of atopic
      dermatitis-like skin lesions in the offspring of NC/Nga mice.

PMID- 19857366
TI  - Comparison of the protective effects of steamed and cooked broccolis on ischaemia
      reperfusion-induced cardiac injury.
AB  - Recently, broccoli, a vegetable of the Brassica family, has been found to protect
      the myocardium from ischaemic reperfusion injury through the redox signalling of
      sulphoraphane, which is being formed from glucosinolate present in this
      vegetable. Since cooked broccoli loses most of its glucosinolate, we assumed that
      fresh broccoli could be a superior cardioprotective agent compared to cooked
      broccoli. To test this, two groups of rats were fed with fresh (steamed) broccoli
      or cooked broccoli for 30 d, while a third group was given vehicle only for the
      same period of time. After 30 d, all the rats were sacrificed, and the isolated
      working hearts were subjected to 30 min ischaemia followed by 2 h of reperfusion.
      Both cooked and steamed broccolis displayed significantly improved post-ischaemic
      ventricular function and reduced myocardial infarction and cardiomyocyte
      apoptosis compared to control, but steamed broccoli showed superior
      cardioprotective abilities compared with the cooked broccoli. Corroborating with
      these results, both cooked and steamed broccolis demonstrated significantly
      enhanced induction of the survival signalling proteins including Bcl2, Akt,
      extracellular signal-regulated kinase 1/2, haemoxygenase-1, NFE2 related factor
      2, superoxide dismutase (SOD1) and SOD2 and down-regulation of the proteins (e.g.
      Bax, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase) of the death
      signalling pathway, steamed broccoli displaying superior results over its cooked
      counterpart. The expressions of proteins of the thioredoxin (Trx) superfamily
      including Trx1 and its precursor sulphoraphane, Trx2 and Trx reductase, were
      enhanced only in the steamed broccoli group. The results of the present study
      documented superior cardioprotective properties of the steamed broccoli over
      cooked broccoli because of the ability of fresh broccoli to perform redox
      signalling of Trx.

PMID- 19857367
TI  - Acute ingestion of resistant starch reduces food intake in healthy adults.
AB  - Resistant starch (RS), a non-viscous dietary fibre, may have postprandial effects
      on appetite regulation and metabolism, although the exact effects and mechanisms
      are unknown. An acute randomised, single-blind crossover study, aimed to
      determine the effects of consumption of 48 g RS on appetite compared to energy
      and available carbohydrate-matched placebo. Twenty young healthy adult males
      consumed either 48 g RS or the placebo divided equally between two mixed meals on
      two separate occasions. Effects on appetite were assessed, using an ad libitum
      test meal and 24-h diet diaries for energy intake, and using visual analogue
      scales for subjective measures. Changes to postprandial glucose, insulin and C
      peptide were also assessed. There was a significantly lower energy intake
      following the RS supplement compared to the placebo supplement at both the ad
      libitum test meal (5241 (sem 313) v. 5606 (sem 345) kJ, P = 0.033) and over the
      24 h (12 603 (sem 519) v. 13 949 (sem 755) kJ, P = 0.044). However, there was no
      associated effect on subjective appetite measures. Postprandial plasma glucose
      concentrations were not significantly different between supplements, but there
      was a significantly lower postprandial insulin response following the RS
      supplement (P = 0.029). The corresponding C-peptide concentrations were not
      significantly different, although the ratio of C-peptide to insulin was higher
      following the RS supplement compared to placebo (P = 0.059). These results
      suggest that consumption of 48 g RS, over a 24-h period, may be useful in the
      management of the metabolic syndrome and appetite. Further studies are required
      to determine the exact mechanisms.

PMID- 19857369
TI  - Haemodynamic changes due to delayed sternal closure in newborns after surgery for
      congenital cardiac malformations.
AB  - BACKGROUND: Delayed sternal closure is used to prevent low cardiac output
      syndrome in selected newborns shortly after cardiac surgery for congenital
      cardiac defects. Sternal closure itself often causes haemodynamic and ventilatory
      instability that cannot be entirely assessed by standard monitoring means.
      Therefore, we used transpulmonary thermodilution technique for an exact
      evaluation of the haemodynamic changes. PATIENTS AND METHODS: Between April,
      2006, and December, 2008, 23 neonates aged from 1 to 30 days, with a median of 7
      days, and weighing from 1.9 to 4.2 kilograms, with a median of 3.25 kilograms,
      were studied after biventricular corrections. Residual intracardiac shunts were
      excluded by echocardiography. Haemodynamic and ventilatory parameters, along with
      those obtained by the transpulmonary thermodilution technique, were recorded
      before and immediately after the sternal closure, and then at 0.5, 1, 2, 6, 12,
      24, and 48 hours. RESULTS: Chest closure caused significant decrease in systolic
      arterial pressure from 80.04 +/- 11.48 to 69.48 +/- 9.63 mmHg (p < 0.001),
      cardiac index from [median (25th/75th centile)] 2.640 (2.355/2.950) to 2.070
      (1.860/2.420) l/min/m2 (p < 0.001), stroke volume index from 18.50 (16.00/20.00)
      to 14.00 (11.00/17.00) ml/m2 (p < 0.001), and dynamic lung compliance from 2.45
      (2.31/3.00) to 2.30 (2.14/2.77) ml/cmH2O (p = 0.007). Stroke volume variation
      increased from 14.00 (9.25/16.75) to 18.00 (15.00/21.00) % (p < 0.001). The
      oxygenation index transitorily increased from 2.50 (2.14/3.15) to 3.36
      (2.63/4.29) (p < 0.001). Serum lactate decreased from 1.40 (1.12/2.27) to 1.0
      (0.8/1.3)mmol/l, p < 0.001 in coincidence with a haemodynamic stabilisation at a
      later time after chest closure. Cardiopulmonary instability caused by the sternal
      closure necessitated therapeutic intervention in 18 of 23 patients (78.3%).
      CONCLUSION: Delayed sternal closure causes a significant transitory decrease in
      stroke volume, cardiac output and arterial blood pressure. Also lung compliance
      and blood oxygenation are temporarily significantly compromised.

PMID- 19857368
TI  - Aortic distensibility and dilation in Turner's syndrome.
AB  - BACKGROUND: Aortic dilation and dissection is reported in patients with Turner's
      syndrome, both with and without cardiovascular risk factors. The bicuspid aortic
      valve is closely associated with dilated aortic root, although expression of
      aortic dilation is variable. The determinants for variable expression of aortic
      dilation in individuals with Turner's syndrome, however, are unknown. HYPOTHESIS:
      A primary mesenchymal defect is prevalent in individuals with Turner's syndrome,
      suggested by having abnormalities in bone matrix, and lymphatic and peripheral
      blood vessels. We hypothesize that an abnormal intrinsic elastic property of
      aorta is a forerunner of aortic dilation in Turner's syndrome. OBJECTIVE: Assess
      utility of aortic distensibility as a measure of aortic elasticity for the
      stratification of the risk for aortic dilation, and its relationship with age,
      karyotype, and hormonal therapy. DESIGN: Prospective cross-sectional study.
      PATIENTS AND METHOD: We performed cross-sectional M-mode and Doppler
      echocardiography in 24 individuals with Turner's syndrome. Dimensions of the
      aortic root, and its distensibility, were calculated using standard techniques.
      We also examined a control group of 24 age matched normotensive patients with
      structurally normal hearts, who had been referred for evaluation of cardiac
      murmurs or chest pain. RESULTS: Aortic dilation was the most common cardiac
      anomaly, seen in 11 of 24 (46%) individuals with Turner's syndrome, and none in
      control group. Of these individuals, 5 without cardiovascular risk factors had
      aortic dilation. In 2 young girls, aortic dimensions were normal, albeit with
      reduced distensibility. Aortic dilation correlated inversely with aortic
      distensibility, but not with age, karyotype or hormonal therapy. CONCLUSION:
      Individuals with Turner's syndrome, even without cardiovascular risk factors, do
      develop aortic dilation accompanied by decreased aortic distensibility,
      suggestive of an intrinsic abnormality in elastic property of the ascending
      aorta.

PMID- 19857370
TI  - Duration and dispersion of the P wave after the Senning operation.
AB  - We studied the duration and dispersion of the P wave in patients after a Senning
      operation, assessing its value in detecting the risk of atrial tachycardias.We
      measured the duration and dispersion of the wave in surface 12 lead
      electrocardiograms obtained from 18 patients with sinus rhythm, having a mean age
      of 12.8 years, with 13 being males and 5 females, who had undergone a Senning
      operation, comparing the values obtained in 35 age and gender-matched healthy
      people. The patients had undergone repair at a mean age of 13.4 months, and had a
      mean duration of follow-up of 12.8 years after the procedure. We also made 24
      hour Holter recordings.The maximal duration of the P wave, at a mean of 129.3
      milliseconds, and dispersion with a mean of 78 milliseconds, were both
      significantly increased in the patients compared with their controls, the mean
      values for the normal subjects being 103.7 and 54 milliseconds. Supraventricular
      tachycardia was detected in 1 of 3 patients with dispersion greater than 100
      milliseconds, and in 2 of 15 patients (13%) with dispersion less than 100
      milliseconds as measured from the Holter recordings (p > 0.05).Thus, the maximum
      duration and dispersion of the P wave were increased in patients after a Senning
      operation, but we were unable to establish any relationship between these
      measurements and atrial tachycardias as observed using Holter monitoring.

PMID- 19857371
TI  - Seeing is a verb.
AB  - This commentary on 'The interaction of attention and action: From seeing action
      to acting on perception' by Humphreys et al. (2010) considers selection-for
      action in relation to the role of parietal cortex corollary discharge in the
      'mastery of sensori-motor contingencies' that O'Regan and Noe (2001) suggest
      gives rise to visual awareness.

PMID- 19857373
TI  - Physically active patients with coronary artery disease: a longitudinal
      investigation of the processes of exercise behaviour change.
AB  - OBJECTIVES: Although regular exercise is important for patients with coronary
      artery disease (CAD), most CAD patients are not sufficiently active. The
      transtheoretical model offers a framework for the process of exercise behaviour
      change. But until today, it is not clear which processes of exercise behaviour
      change (POC) support CAD patients in maintaining exercise after discharge.
      DESIGN: A longitudinal study with baseline measure and 6-month follow-up has been
      conducted. German CAD patients were mailed at home after discharge. POC and
      exercise were self-reported. METHODS: A total of 204 CAD patients were selected
      from five rehabilitation centres. A total of 108 CAD patients, which were in the
      post-action stages, provided data at baseline and follow-up. Two different
      analyses were carried out. Firstly, structural equation modelling with baseline
      data (N=147) was used to test the hierarchical order of the POC in experiential
      and behavioural processes. Secondly, cross-lagged panel analysis was used to
      investigate whether POC lead to exercise or vice versa and which POC support CAD
      patients in maintaining exercise. RESULTS: Comparative analysis indicates that
      the two hierarchical-factor model fits the data significantly better than the one
      hierarchical-factor model (chi(2)diff((1))=19.04, p<.001), even though
      experiential and behavioural processes are highly correlated (r=.98, p<.001).
      Standardized effects of the antecedent cross-lags are significant for
      consciousness raising (beta=0.27), reinforcement management (beta=0.28), self
      liberation (beta=0.28), and stimulus control (beta=0.33) indicating that these
      POC are predictive for CAD patients maintaining exercise. CONCLUSION: Although
      some POC support the exercise behaviour change process and the hierarchical
      structure is apparent, it may be beneficial to adapt the POC to give a more
      precise understanding of the change processes.

PMID- 19857372
TI  - Do image descriptions underlie word recognition in reading?
AB  - This article is a commentary on 'The utility of image descriptions in the initial
      stages of vision: A case study of printed text' (Watt & Dakin, 2010).

PMID- 19857374
TI  - Young adults' social drinking as explained by an augmented theory of planned
      behaviour: the roles of prototypes, willingness, and gender.
AB  - OBJECTIVE: This study focused on young adults' alcohol consumption in social
      contexts. A dual-process model (including reasoned action and social reaction)
      was applied by combining the theory of planned behaviour (TPB) and the
      prototype/willingness model. A key question was whether willingness and actor and
      abstainer prototype variables would augment the TPB by increasing explained
      variance. DESIGN: Participants completed questionnaires prior to spending an
      evening socializing over the weekend (Time 1). Behavioural data were obtained by
      telephone interviews a few days after the social drinking occasion (Time 2).
      METHOD: N=300 people (mean age 25 years) took part in the study. The outcome
      measure of pure alcohol in grams was calculated based on participants' reports
      about their consumed drinks. Multigroup path analyses were conducted because of
      sex differences on behavioural and psychological variables. RESULTS: The TPB
      explained 35% of the variance in men's and 41% in women's alcohol consumption.
      Augmentation with prototype perception and willingness contributed significantly
      to the prediction of intention (DeltaR(2)=.07) and alcohol consumption for men
      (DeltaR(2)=.14). A significant interaction implied that willingness led to heavy
      drinking particularly among those men who made negative evaluations of the
      abstainer prototype. CONCLUSION: Women's alcohol consumption is explained by TPB
      variables via a more controlled reasoned-action path only, whereas additional
      processes (e.g., pursuing the actor image intentionally, rejecting the abstainer
      image more intuitively) are important for men. The moderating role of gender is
      discussed in light of traditional gender roles and recent trends in alcohol
      consumption.

PMID- 19857375
TI  - Interpretation of self-talk and post-lecture affective states of higher education
      students: a self-determination theory perspective.
AB  - BACKGROUND: Self-determination theory posits that informational versus
      controlling interpretations of intra-personal events have positive and negative
      implications, respectively, for well-being. Self-talk represents an intra
      personal event that could be interpreted as informational or controlling and may
      attenuate or exacerbate the negative effects of a stressful experience. AIMS: The
      present study investigated relationships between students' informational and
      controlling interpretations of self-talk, and their post-lecture affective state.
      An interactive hypothesis, whereby self-talk would be more strongly associated
      with well-being when students reported experiencing the lecture as stressful, was
      also tested. SAMPLE: Participants were 146 male and female undergraduate students
      (M age=19.25, SD=2.57) enrolled on research methods/statistics modules. METHODS:
      Immediately post-lecture, participants completed a measure of informational and
      controlling self-talk, short forms of the State-Trait Anxiety Inventory and the
      Positive and Negative Affect Scale, and self-report measures of their experience
      and understanding of the lecture. RESULTS: Findings from moderated hierarchical
      regression analyses indicated that informational self-talk was positively
      associated with positive affect regardless of students' experience or
      understanding of a lecture. Significant interactions were found between
      controlling self-talk and experience and understanding, in that a negative
      experience or poor understanding predicted higher state anxiety and negative
      affect when students used high, but not low, levels of controlling self-talk.
      CONCLUSIONS: The functional significance of students' self-talk may have
      implications for affect in higher education, suggesting that providers should
      promote the use of self-talk that emphasizses students' autonomy and competence.

PMID- 19857376
TI  - Understanding words, understanding numbers: an exploration of the mathematical
      profiles of poor comprehenders.
AB  - BACKGROUND: Poor comprehenders are children who show significant deficits in
      their reading comprehension performance, despite average, or above-average word
      reading ability. To date, there have been no in-depth studies of the mathematical
      performance profiles of such children. AIMS: This study aimed to explore the
      mathematical profiles of poor comprehenders. Given that language impairment is
      associated with difficulties with mathematics, and that poor comprehenders tend
      to have oral language weaknesses, we hypothesized that poor comprehenders would
      show relative weaknesses in aspects of mathematical performance. SAMPLE: From a
      sample of 109 children aged 7-8 years, we selected 14 poor comprehenders and 14
      controls with age-appropriate reading comprehension ability. The groups were
      matched on non-verbal ability, multiple measures of reading accuracy, and
      chronological age. METHODS: We compared the performance of the group of poor
      comprehenders with that of the matched controls on two standardized measures of
      mathematical ability, one measuring procedural arithmetic prowess and the other
      tapping higher-level mathematical reasoning. RESULTS: Although there were no
      group differences in performance on the arithmetic measure, the poor
      comprehenders showed significantly lower scores than the controls on the
      mathematical reasoning task. The poor comprehenders exhibited impaired verbal
      ability relative to controls, with these differences in verbal ability associated
      with the group differences found on the test of mathematical reasoning.
      CONCLUSIONS: Poor comprehenders' deficits are not limited to the domain of
      literacy; their underlying profile of impairments also seems to selectively
      impact on certain components of mathematical ability.

PMID- 19857377
TI  - Assessment of cognitive abilities in multiethnic countries: the case of the Wolof
      and Mandinka in the Gambia.
AB  - BACKGROUND: The use of cognitive tests is increasing in Africa but little is
      known about how such tests are affected by the great ethnic and linguistic
      diversity on the continent. AIM: To assess ethnic and linguistic group
      differences in cognitive test performance in the West African country of the
      Gambia and to investigate the sources of these differences. SAMPLES: Study 1
      included 579 participants aged 14-19 years from the Wolof and Mandinka ethnic
      groups of the Gambia. Study 2 included 41 participants aged 12-18 years from the
      two ethnic groups. METHODS: Study 1 assessed performance on six cognitive tests.
      Participants were also asked about their history of education, residence in the
      city, parental education, and family socio-economic status. Study 2 assessed
      performance on two versions of the digit span test. Recall of the numbers 1-5
      were compared with recall of numbers 1-9 for both the Wolof (who count in base 5)
      and the Mandinka (who count in base 10). RESULTS: Study 1 established that Wolof
      performance was lower than that of the Mandinka on five out of six cognitive
      tests. In four of these tests, group differences were partially mediated by
      participation in primary school and migration to the city. Group differences were
      substantial for the digit span test and were not attenuated by mediating
      variables. Study 2 found that digit span among the Wolof was shorter than that of
      the Mandinka for numbers 1-9 but not for numbers 1-5. CONCLUSIONS: Several
      suggestions are made on how to consider the ethnicity, language, education, and
      residence (urban vs. rural) of groups when conducting comparative cognitive
      assessments or collecting normative data.

PMID- 19857378
TI  - An exploration of the presence and content of metacognitive beliefs about
      depressive rumination in Pakistani women.
AB  - OBJECTIVES: To explore the experience of depression in Pakistani women, the
      coping strategies employed, and the presence and content of metacognitive beliefs
      about rumination. METHODS: Seven semi-structured interviews were conducted with
      Pakistani women and analysed using template analysis with the inclusion of a
      priori themes. RESULTS: Women's experiences of depression consisted of
      descriptions of physical, behavioural, and psychological symptoms, as well as
      their understandings of depression including being alone with their problems and
      the factors that caused their depression. Coping strategies they employed
      included talking to someone, distraction; using antidepressant medication and
      positive self-talk. Consideration of rumination included descriptions of the
      content being largely past-focused and around 'why?'. Both negative and positive
      beliefs about rumination were revealed. CONCLUSIONS: Depression was seen as a
      very lonely experience, which had an impact on their physical and psychological
      health. Women demonstrated an understanding of the interplay between their
      emotional experience, ways of thinking, physical health, and behaviour. On the
      whole, results were consistent with the clinical metacognitive model of
      depression in that both positive and negative beliefs about rumination were
      evident for most of the women. However, positive beliefs did not appear to be as
      universally endorsed as previous findings have found - possible explanations are
      discussed. Clinical implications and ideas for future research are outlined.

PMID- 19857379
TI  - Update on invasive opportunistic mycoses: clinical trials review, 2008-2009.
AB  - Invasive fungal infections remain major causes for morbidity and mortality in
      severely ill or immunocompromised patients. The past decade saw major expansion
      in the antifungal armamentarium, and the precise role of newer antifungal agents
      continues to be defined through clinical trials. This article summarizes five of
      the most relevant clinical trials related to prevention and treatment of
      opportunistic fungal infections in adult patients published between 2008 and
      2009.

PMID- 19857380
TI  - Risk-based antifungal prophylaxis in hematologic malignancy and stem cell
      transplantation.
AB  - Invasive fungal infection (IFI) is an important cause of morbidity and mortality
      in patients with hematologic malignancy, prolonged neutropenia, or after
      hematopoietic stem cell transplant. Antifungal prophylaxis prevents IFI in high
      risk hematology patients. This article discusses recent developments in
      antifungal prophylaxis, focusing on those expected to affect patient management.
      Significant advances have occurred in understanding risk stratification and
      assessment of individual patient risk for drug-drug interactions, toxicity, or
      variations in pharmacokinetics; choice of antifungal prophylaxis strategy, drug,
      dose, route, and regimen; therapeutic drug monitoring; cost effectiveness of
      prophylaxis; and the significance of breakthrough IFI. Research over the coming
      decade is likely to fundamentally alter antifungal prophylaxis by allowing
      clinicians to make individualized decisions for their patients informed by rapid,
      detailed, and personalized risk-benefit analyses.

PMID- 19857381
TI  - Prophylaxis of invasive mycoses in solid organ transplantation.
AB  - Solid organ transplantation is emerging as a lifesaving procedure for increasing
      numbers of patients, and invasive fungal infections are a significant cause of
      mortality and morbidity for patients undergoing such procedures. Risks for
      developing these infections are continuing to evolve, leading to shifts in the
      epidemiology of invasive mycoses occurring after transplantation. Targeting
      preventive efforts to select solid organ transplantation groups at highest risk
      for invasive fungal infections is critical to optimizing prophylaxis strategies.
      The epidemiology of posttransplantation fungal infections, antifungal drug
      interactions and side effects, and new diagnostic capabilities should be
      considered when choosing an approach to antifungal prophylaxis for this
      population.

PMID- 19857382
TI  - New immunosuppressive agents and risk for invasive fungal infections.
AB  - Increased numbers of invasive fungal infections (IFI) were reported in patients
      treated with newer immunosuppressive drugs such as tumor necrosis factor (TNF)
      alpha antagonists, the anti-CD52 antibody alemtuzumab, or the interleukin-2
      receptor antibody basiliximab. These drugs are administered to patients who have
      autoimmune inflammatory diseases and lymphoid malignancies, or are recipients of
      solid organ or allogeneic hematopoietic stem cell transplants. IFI risk is higher
      in patients receiving TNF-alpha blockers or alemtuzumab late in the course of
      disease and in those with a history of IFI. Incidence and mortality rates of IFI
      are confounded by frequent, multiple comedications, heterogeneous definitions for
      IFI, and a presumed reporting bias. For filamentous molds and endemic fungal
      infections, different regional prevalence rates must be considered. Generally,
      invasive infections are more frequent among these groups and thus are important
      considerations in the management of patients receiving these immunosuppressive
      drugs.

PMID- 19857383
TI  - What is the role of therapeutic drug monitoring in antifungal therapy?
AB  - Despite an expanding number of therapeutic options for treating invasive fungal
      infection (IFI), the mortality rate from these infections remains high. Many risk
      factors for poor outcome from IFI (eg, the compromised immune status of the host)
      are not modifiable by the treating clinician. Thus, elevated interest exists in
      any modifiable factor that might improve outcome. Many of the new antifungal
      agents have marked variability in drug concentration based on either inconsistent
      absorption or elimination, leading to very wide interpatient variability. Many
      agents also have a narrow therapeutic index, meaning a small range between drug
      levels too low to achieve the desired clinical benefit and high enough to produce
      unwanted or toxic effects. Therefore, therapeutic drug monitoring is useful to
      maximize efficacy while minimizing drug toxicity of some antifungal agents.

PMID- 19857384
TI  - Genitourinary manifestations of epstein-barr virus infections.
AB  - Epstein-Barr virus (EBV) is best known as the organism responsible for the
      syndrome of acute infectious mononucleosis. Transmission of EBV most commonly
      occurs through oral secretions. EBV has also been isolated from the female
      genital tract, where its role is poorly understood. This article reviews the
      available literature and data regarding EBV in the female genital tract and
      discusses areas of consensus and controversy. The primary manifestation of EBV
      seems to be vulvar ulcers, which are underrecognized. Diagnosis relies on
      appropriate serologic testing. Management includes local care and may require
      pain and corticosteroid medications. Although EBV is present elsewhere in the
      female genital tract, its pathogenic role in the cervix, uterus, fallopian tubes,
      and ovaries is poorly understood.

PMID- 19857385
TI  - New concepts in understanding genital herpes.
AB  - Herpes simplex virus (HSV)-2 is a lifelong infection that causes recurrent
      genital ulcers and, rarely, disseminated and visceral disease. HSV-1 infection is
      an increasingly important cause of genital ulcers. HSV infections are the most
      common cause of genital ulcers in adults, but acquisition and chronic infection
      are more commonly asymptomatic than symptomatic. Both the symptomatic and
      asymptomatic forms of HSV are of clinical consequence for several reasons. HSV-2
      infection enhances HIV-1 acquisition and transmission. In addition, sexual and
      perinatal transmission can occur during asymptomatic viral shedding. Perinatal
      transmission is of particular concern because neonatal HSV infection results in
      severe morbidity to the newborn. Antiviral medicines are effective for limiting
      recurrence duration and decreasing transmission likelihood, although no available
      intervention completely prevents transmission. This fact highlights the
      importance of laboratory diagnostics for this lifelong infection, and the need
      for an HSV vaccine.

PMID- 19857386
TI  - MRSA infection of buttocks, vulva, and genital tract in women.
AB  - Staphylococcus aureus, although a common commensal bacterium, is a frequent cause
      of skin and soft tissue infections as well as life-threatening blood stream
      infections. Resistance to methicillin, which previously was associated with only
      hospitalized patients, has become a common community-based phenomenon. Less well
      known is S. aureus vaginal colonization and heterosexual transmission, mainly by
      skin-mucosa contact. Recognizing the vagina as a reservoir is important and
      should not be ignored, particularly in women presenting with recurrent genital
      and buttock boils or if their sexual partner has such infections. Vaginal
      cultures should be obtained from such women; if the vagina is found to be
      colonized, eradication of S. aureus from the vagina should be attempted to reduce
      infection recurrence.

PMID- 19857387
TI  - Antibiotic consideration in bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is a syndrome characterized by the loss of indigenous
      vaginal lactobacilli and massive polymicrobial anaerobic vaginal overgrowth of
      elusive etiology. Although progress has occurred in defining the composition of
      the vaginal microbiome using DNA amplifications, rapidly accumulating data have
      not resulted in therapeutic advantage. Treatment options remain limited and
      outcome often unsatisfactory, particularly regarding the frequent recurrence of
      symptomatic disease, leading to enormous frustration among patients and
      practitioners. This review does not address the important issues of transmission,
      diagnosis, and complications of BV, but focuses on antimicrobial activity of
      current drugs and their limitations in vitro and in vivo. Recognizing these
      limitations should allow for either development of new antibiotics or for
      innovative use of currently available drugs in new study protocols.

PMID- 19857388
TI  - HIV and the Kidney.
AB  - Direct effects of HIV-1 infection on the kidney combine with immune and genetic
      factors, comorbidities, coinfections, and medication toxicities to induce a
      spectrum of kidney disorders in HIV disease. The most dramatic of these, HIV
      associated nephropathy (HIVAN), emerges almost exclusively in persons of African
      descent and is associated with rapid progression to end-stage renal disease in
      the absence of antiretroviral therapy (ART). ART modifies the natural history of
      HIVAN, but the renal benefits of ART may not be limited to HIVAN. ART is often
      under prescribed or incorrectly dosed in persons with kidney disease. Vigilant
      attention to renal function and an understanding of the complex associations
      involving the kidneys are necessary for optimal care of these patients.

PMID- 19857389
TI  - Update on immune reconstitution inflammatory syndrome: progress and unanswered
      questions.
AB  - The immune reconstitution inflammatory syndrome (IRIS) is characterized by
      clinical deterioration occurring after the initiation of effective antiretroviral
      therapy (ART) and results from a disordered and exuberant immune response. The
      syndrome may present as paradoxical IRIS or unmasking IRIS, depending on whether
      an opportunistic infection was recognized and treated before ART initiation.
      Numerous descriptions of IRIS caused by many pathogens were published in the
      years after the introduction of effective ART. In recent years, with enhanced
      rollout of ART in resource-limited settings, attention has again focused on IRIS
      because of the enormous burden of opportunistic infections. This review
      highlights recent findings elucidating risk factors for and the pathogenesis and
      treatment of IRIS.

PMID- 19857390
TI  - [Climate and health].

PMID- 19857391
TI  - [The climate challenge is a health challenge].

PMID- 19857392
TI  - [Climate changes caused by man].
AB  - This article provides a brief overview over some of the main findings in the most
      recent IPCC WG I report and in articles published after the report. It is argued
      that the conclusions in the report on observed climate variations and trends
      during the last 100 years have been largely confirmed or even reinforced by the
      most recent studies. Concerning future climate change, new analyses of possible
      changes in sea-level, which take melting land ice into account, indicate that the
      global sea level may rise as much as one meter within the present century.

PMID- 19857393
TI  - [Air quality and climate change].
AB  - Air quality, health and climate change are closely connected. Ozone depends on
      temperature and the greenhouse gas methane from cattle and biomass. Pollen
      presence depends on temperature and CO2. The effect of climate change on
      particulate air pollution is complex, but the likely net effect is greater health
      risks. Reduction of greenhouse-gas emissions by reduced livestock production and
      use of combustion for energy production, transport and heating will also improve
      air quality. Energy savings in buildings and use of CO2 neutral fuels should not
      deteriorate indoor and outdoor air quality.

PMID- 19857394
TI  - [Nosocomial infections--ecological niches].
AB  - Knowledge of ecological niches of nosocomial pathogens is used in treatment and
      prevention of nosocomial infections. This article offers an analysis of the
      ecological niches of three important nosocomial pathogens: Clostridium difficile,
      Staphylococcus aureus and Legionella pneumophila. Relevant terms are explained
      and examples of deliberate and non-deliberate manipulation of the niches and the
      following consequences are given. Finally, the consequences of climate changes on
      the pattern of nosocomial infections are discussed.

PMID- 19857395
TI  - [Climate- and vector-borne diseases].
AB  - The predicted changes in climate have raised concerns that vector-borne diseases
      may emerge or expand in tempered regions. Malaria, leishmaniasis and tick-borne
      illnesses are discussed in terms of climate change and their endemic potential,
      especially in Denmark. While climate may play an important role in disease
      patterns, it is evident that transmission potential is governed by a complex of
      factors, including socio-economy, health-care capacity and ecology. In Denmark,
      malaria and leishmaniasis are unlikely to become public health problems, whereas
      the potential for tick-borne illnesses may increase.

PMID- 19857396
TI  - [Infectious diseases and climate change].
AB  - Climate changes will likely have an impact on the spectrum of infectious diseases
      in Europe. We may see an increase in vector-borne diseases, diseases spread by
      rodents such as Hantavirus, and food- and water-borne diseases. As the effects of
      climate changes are likely to occur gradually, a modern industrialised country
      such as Denmark will have the opportunity to adapt to the expected changes.

PMID- 19857397
TI  - [Climate change, food production and human health].
AB  - Production of livestock accounts for 18% of anthropogenic greenhouse gas
      emissions. Although livestock products can alleviate malnutrition in poor
      countries, they are associated with diseases of affluence in wealthy countries.
      Red meat (pork, beef, sheep and goat), especially, is associated with higher
      rates of death due to cardiovascular disease and cancer. A policy of reducing
      consumption of red meat in wealthy countries and encouraging a limited
      consumption increase in poor countries would benefit the climate as well as human
      health.

PMID- 19857398
TI  - [Allergic disease--pollen allergy and climate change].
AB  - Pollen allergy currently affects a fifth of the population. A warmer climate will
      lead to a longer pollen season and more days with high pollen counts. In
      addition, a warmer climate increases the risk of proliferation of new plants with
      well-known allergenic pollens like ragweed, plane tree and wall pellitory, which
      have not previously caused allergy in Denmark. The consequences will be more
      people with hay fever and pollen asthma, longer allergy seasons and an increase
      in the severity of symptoms, disease-related costs and demands on health care for
      diagnosis and treatment of more complex allergies.

PMID- 19857399
TI  - [Climate change and consequences for the elderly].
AB  - Heat waves may cause increased mortality, especially among frail elderly. The
      consequences of heat waves can be prevented by reducing indoor temperature,
      increasing intake of water with relevant electrolytes and ongoing assessment of
      medication and chronic disease. The regional and municipal administrative bodies
      should create management plans for heat waves and other extreme weather
      situations.

PMID- 19857400
TI  - [Migration, climate and health].
AB  - Many tentative connections have been postulated between migration and climate.
      This article points to rural-urban migration, particularly into low elevation
      urban slums prone to flooding as an issue needing urgent attention by health
      professionals. It also notes the no-man's land in which environmental refugees
      find themselves and the consequences this may have. Finally, it points to the
      urgent need to reform health systems in both developing and developed countries
      to adapt to rapidly changing disease patterns and to become more responsive to
      them.

PMID- 19857401
TI  - [Lifestyle and climate change].
AB  - The majority of physicians are aware of the urgency of preventing major global
      warming, and of the global health consequences such warming could bring.
      Therefore, we should perhaps be more motivated to mitigate these climate changes.
      The Danish Medical Association should stress the importance of preventing major
      global climate health disasters, and the need for ambitious international
      reduction agreements. In our advice and treatment of patients, focus could be on
      mutually shared strategies comprising mitigation of global warming and changing
      of life-style habits to improve our general health.

PMID- 19857402
TI  - [Potentially beneficial effects of climate changes].
AB  - Climate changes have many unbeneficial effects on human health, but may also have
      beneficial effects. An increased mean temperature reduces the incidence of death
      due to hypothermia and cardiovascular disease and may increase exercise
      frequency. As the ozone layer decreases, the synthesis of vitamin D in the
      organism will also increase. An increased level of plasma vitamin D has
      beneficial effects on bone- and muscle health, seems to reduce cancer incidence
      and mortality and reduces the prevalence of autoimmune- and cardiovascular
      disease.

PMID- 19857403
TI  - [Climate chance and research activity].
AB  - There are three main focus areas relevant to health in research related to
      climate change: 1) disentangling of the complex associations between climate
      sensitive risk factors and health 2) guidance as to where, when and how effective
      health adaptation strategies may be implemented for maximum effect, and 3) health
      impact assessment (with a focus on health co-benefits) of climate-related
      policies in other sectors. Further development in each of these areas will
      provide important opportunities for strengthening health promotion and
      protection.

PMID- 19857404
TI  - [Implementation of new knowledge in times of climate change?].
AB  - Climate change is the primary threat to public health in the 21st century. There
      is a huge need for creation of new knowledge on how most effectively and
      efficiently to respond to the negative effects on health. Participatory research
      and development projects may be essential in creation and dissemination of new
      knowledge. Theoretically underpinned interventions and implementation strategies
      are necessary to ensure that knowledge is translated into action. Universities
      and health care organisations have a central role in preparing future health
      professionals by giving them the skills and knowledge needed.

PMID- 19857405
TI  - Determination of difficult intubation in the ED.
AB  - OBJECTIVE: The aim of this study is to determine the predictors of difficult
      intubation in the emergency setting. METHODS: This prospective observational
      clinical study was conducted in the emergency department (ED) of a University
      Hospital with an annually census of 50 000 visits from May 2005 to May 2007. All
      patients requiring intubation in the ED were included into the study. During the
      study period, same airway management protocol was used all intubations. The study
      form included patient's demographic and variables according to intubation such as
      the Cormack-Lehane grade, modified LEMON score, Glasgow Coma Scale score, success
      rate, and associated complications. RESULTS: A total of 366 patients were
      included in the study. The mean age of the study patients was 46.8 +/- 22.8, and
      68.6% (n = 251) of them were male. A total of 86 (23.5%) patients were classified
      in the difficult intubation group and 280 (76.5%) patients in easy intubation
      group. Logistic regression analysis performed by the variables found to be
      significant in the univariate analysis revealed thyroid-to-hyoid distance less
      than 2 fingers (odds ratio, 3.34; 95% confidence interval, 1.35-8.27; P = .009)
      as an independent factor complicating the intubation. Cormack and Lehane
      classification was strongly related to difficult intubation. Intubation was more
      difficult from grade 1 to 4 (11% vs 25.2% vs 34% vs 81.8%, respectively; P =
      .000). CONCLUSIONS: The thyroid-to-hyoid distance less than 2 fingers is the only
      independent variable in predicting difficult intubation. Mallampati
      classification is not a useful tool in classifying the difficult intubation in
      the ED that the "LEMON" acrostic can be modified to "LEON".

PMID- 19857406
TI  - Incidence and onset of delayed seizures after overdoses of extended-release
      bupropion.
AB  - BACKGROUND: Delayed seizures have been reported with overdoses of bupropion
      extended-release (XL). This study systematically evaluates the frequency and
      timing of seizures and an association between other toxic effects (ie, agitation,
      tremors, and hallucinations) and seizures. METHODS: A 3-year multi-poison center
      observational study of hospitalized patients with ingestion of bupropion XL
      >or=600 mg in adults and >or=4 mg/kg in children was performed. Patients with
      coingestants or a medical history that could affect seizure occurrence were
      excluded. Data collection forms captured onset time of seizure(s), other
      symptoms, and treatment. RESULTS: One hundred seventeen patients met inclusion
      criteria: median age of 22 years (range, 1.3-65 years) with 16 children <or= 3
      years. Seizures occurred in 37 (31.6%) patients, with initial seizure at 0.5 to
      24 hours after ingestion; 12 (32%) patients had initial seizure at > 8 hours.
      Subsequent seizures occurred in 49%. Children ages 1.3, 3, and 7 years, developed
      seizures. In patients >or= 13 years of age, median dose with seizures was 4350 mg
      (range, 600-54 000) compared to 2400 mg (range, 600-9000) in patients without
      seizures. Agitation, tremors, and hallucinations occurred in 29.7%, 40.5%, and
      18.9% of patients with seizures, respectively, compared with 12.5 %, 17.5%, and
      10% in patients without seizures. The neurologic effects agitation (P = .045) and
      tremors (P = .005) occurred more frequently. CONCLUSION: Delayed seizure onset
      suggests a minimum observation period of 24 hours after bupropion XL overdose.
      Although patients experiencing agitation or tremors may be at greater risk,
      seizures can occur without preceding central nervous system toxicity.

PMID- 19857407
TI  - Lack of association between left bundle-branch block and acute myocardial
      infarction in symptomatic ED patients.
AB  - OBJECTIVE: Guidelines recommend treating patients with a new or presumed new left
      bundle-branch block (LBBB) similar to those with an acute ST-segment elevation
      myocardial infarction. It is often unclear which emergency department (ED)
      patients with potentially ischemic symptoms actually have an acute myocardial
      infarction (AMI), even in the setting of LBBB. Our null hypothesis was that in ED
      patients with potential AMI, the presence of a new or presumed new LBBB would not
      predict an increased likelihood of AMI. METHODS: This was an observational cohort
      study. Patients older than 30 years who presented with chest pain or other
      ischemic equivalent and had an electrocardiogram (ECG) to evaluate potential
      acute coronary syndrome (ACS) were enrolled. Data collected include demographics,
      history, ECG, and cardiac markers. Electrocardiograms were classified according
      to the standardized guidelines, including LBBB not known to be old (new or
      presumed new LBBB), LBBB known to be old, or no LBBB. The hospital course was
      followed, and 30-day follow-up was performed on all patients. Our main outcome
      was AMI. RESULTS: There were 7937 visits (mean age, 54.3 +/- 15 years, 57%
      female, 68% black): 55 had new or presumed new LBBB, 136 had old LBBB, and 7746
      had no LBBB. The rate of AMI was not significantly different between the 3 groups
      (7.3% vs 5.2% vs 6.1%; P = .75). Revascularization (7.8% vs old 5.2% vs 4.3%; P =
      .04) and coronary artery disease were more common in patients with new or
      presumed new LBBB (19.2% vs 11.9% vs 10.1%; P = .0004). CONCLUSIONS: Despite
      guideline recommendations that patients with potential ACS and new or presumed
      new LBBB should be treated similar to STEMI, ED patients with a new or presumed
      new LBBB are not at increased risk of AMI. In fact, the presence of LBBB, whether
      new or old, did not predict AMI. Caution should be used in applying
      recommendations derived from patients with definite AMI to ED patients with
      potential ACS that may or may not be sustaining an AMI.

PMID- 19857408
TI  - Sexual assault in postmenopausal women: epidemiology and patterns of genital
      injury.
AB  - STUDY OBJECTIVE: Physical abuse of older women, including reports of sexual
      assault, has risen rapidly for the last decade. The purpose of this study was to
      compare a group of postmenopausal victims of sexual assault with younger adult
      women (18-39 years old) by examining patient demographics, assault
      characteristics, and patterns of physical injury. METHODS: We conducted a
      retrospective cohort analysis to assess epidemiology and anogenital injuries in
      consecutive female victims presenting to sexual assault clinics and/or emergency
      departments within 3 counties of Western Michigan. All patients were examined by
      forensic nurses trained to perform medicolegal evaluations using colposcopy with
      nuclear staining. Patient demographics, assault characteristics, and injury
      patterns were recorded using a standardized classification system. Data from 2
      patient groups (women aged 18-39 years vs postmenopausal women >or=50 years) were
      compared using chi(2) and t tests. RESULTS: During the 5-year study period, 1917
      adult sexual assault victims met the inclusion criteria and comprised the study
      population as follows: 84% of the victims were 18 to 39 years old, and 4% were
      postmenopausal women at least 50 years old. The 72 postmenopausal victims were
      more likely to be assaulted by a single assailant, typically a stranger (56% vs
      32%, P = .008), in their own home (74% vs 46%, P < .001) and experienced more
      physical coercion (72% vs 36%, P < .001). In comparison, the younger control
      group was more likely to have used alcohol or illicit drugs before the assault
      (53% vs 18%, P < .001) and have a history of sexual assault (51% vs 15%, P <
      .001). Postmenopausal victims had a greater mean number of nongenital (2.3 vs
      1.2, P < .001) as well as anogenital injuries (2.5 vs 1.8, P < .001). The
      localized pattern and type of physical injuries were similar in both groups,
      although postmenopausal women tended to have more anogenital lacerations and
      abrasions. CONCLUSION: The postmenopausal woman is not immune from sexual
      assault. The epidemiology of sexual trauma in this age group is uniquely
      different when compared to younger women, which may be useful in planning
      intervention and prevention strategies.

PMID- 19857409
TI  - Urinalysis is not reliable to detect a urinary tract infection in febrile infants
      presenting to the ED.
AB  - OBJECTIVE: Urinary tract infections are a common source of serious bacterial
      infections in febrile infants younger than 2 years. Our objective was to compare
      urinalysis with urine culture in the emergency department evaluation of febrile
      infants. METHODS: A febrile infant registry was instituted at a tertiary care
      hospital treating an average of 55000 patients annually (27% children), from
      December 2002 to December 2003. Patients were eligible if they were younger than
      3 months and had a temperature of at least 38 degrees C or if they were between 3
      and 24 months of age and had a temperature of at least 39 degrees C. Data
      abstracted included age, sex, and temperature. Urinalysis (UA) and urine culture
      (UCx) results were obtained from electronic hospital archives. RESULTS: Nine
      hundred eighty-five patients were entered into the febrile infant registry. Male
      patients comprised 55%. The mean age of patients was 12.6 months; median was 12
      months. Four hundred thirty-five (78% of eligible patients) had both a UA and UCx
      from the same specimen, and there were 45 (10.3%) positive UCx result. Females
      accounted for 33 (73%) of 45 positive results. The sensitivity of UA for
      predicting a positive UCx result was 64% (95% confidence interval [CI], 49%-78%),
      whereas the specificity was 91% (95% CI, 88%-94%). The positive predictive value
      was 46% (95% CI, 31%-53%), with a negative predictive value of 96% (95% CI, 93%
      97%). CONCLUSION: Urinalysis is not reliable for the detection of urinary tract
      infections in febrile infants when compared with urine cultures.

PMID- 19857410
TI  - Outcomes after accidental pediatric ingestions of (dextro)amphetamine and
      methylphenidate.

PMID- 19857411
TI  - Dose-response of vasopressin in a rat model of asphyxial cardiac arrest.
AB  - The advantage of vasopressin over epinephrine in the treatment of cardiac arrest
      (CA) is still being debated, and it is not clear whether a high dose of
      vasopressin is beneficial or detrimental during or after cardiopulmonary
      resuscitation (CPR) in a rat model of CA. In this study, asphyxial CA was induced
      in 40 male Sprague-Dawley rats. After 10 minutes of asphyxia, CPR was initiated;
      and the effects of different doses of vasopressin (low dose, 0.4 U/kg; medium
      dose, 0.8 U/kg; and high dose, 2.4 U/kg; intravenous; n = 10 in each group) and a
      saline control (isotonic sodium chloride solution, 1 mL, intravenous) were
      compared. Outcome measures included the rate of restoration of spontaneous
      circulation (ROSC) and changes of hemodynamic and respiratory variables after
      ROSC. The rates of ROSC were 1 of 10 in the saline group and 8 of 10 in each of
      the 3 vasopressin groups. There were no differences in mean aortic pressure or
      changes of respiratory function after CPR among the vasopressin groups. However,
      the heart rate was lower in the high-dose vasopressin group than in the low- and
      medium-dose groups. These findings indicate that different doses of vasopressin
      result in a similar outcome of CPR, with no additional benefits afforded by a
      high dose of vasopressin during or after CPR, in a rat model of asphyxial CA. The
      mechanism and physiologic significance of the relative bradycardia that occurred
      in the high-dose vasopressin group are currently unknown and require further
      investigation.

PMID- 19857412
TI  - Pediatric myocarditis: presenting clinical characteristics.
AB  - OBJECTIVE: The objective of the study was to characterize the clinical profiles
      of pediatric patients with acute myocarditis and dilated cardiomyopathy (DCM)
      before diagnosis. METHODS: A retrospective cross-sectional study was conducted to
      identify patients with myocarditis and DCM who presented over a 10-year span at 2
      tertiary care pediatric hospitals. Patients were identified based on the
      International Classification of Diseases, Ninth Revision, diagnostic codes.
      RESULTS: A total of 693 charts were reviewed. Sixty-two patients were enrolled in
      the study. Twenty-four (39%) patients had a final diagnosis of myocarditis, and
      38 (61%) had DCM. Of the 62 patients initially evaluated, 10 were diagnosed with
      myocarditis or DCM immediately, leaving 52 patients who required subsequent
      evaluation before a diagnosis was determined. Study patients had a mean age of
      3.5 years, 47% were male, and 53% were female. Common primary complaints were
      shortness of breath, vomiting, poor feeding, upper respiratory infection (URI),
      and fever. Common examination findings were tachypnea, hepatomegaly, respiratory
      distress, fever, and abnormal lung examination result. Sixty-three percent had
      cardiomegaly on chest x-ray, and all had an abnormal electrocardiogram results.
      CONCLUSIONS: These data suggest children with acute myocarditis and DCM most
      commonly present with difficulty breathing. Myocarditis and DCM may mimic other
      respiratory or viral illnesses, but hepatomegaly or the finding of cardiomegaly
      and an abnormal electrocardiogram result may help distinguish these diagnoses
      from other more common pediatric illnesses.

PMID- 19857413
TI  - Effect of introduction of electronic patient reporting on the duration of
      ambulance calls.
AB  - OBJECTIVES: We examined the effect of the change from paper records to the
      electronic patient records (EPRs) on ambulance call duration. METHODS: We
      retrieved call duration times 6 months before (group 1) and 6 months after (group
      2) the introduction of EPR. Subgroup analysis of group 2 was fulfilled depending
      whether the calls were made during the first or last 3 months after EPR
      introduction. RESULTS: We analyzed 37 599 ambulance calls (17 950 were in group 1
      and 19 649 were in group 2). The median call duration in group 1 was 48 minutes
      and in group 2 was 49 minutes (P = .008). In group 2, call duration was longer
      during the first 3 months after EPR introduction. In multiple linear regression
      analysis, urgency category (P < .0001), unit level (P < .0001), and
      transportation decision (P < .0001) influenced the call duration. The
      documentation method was not a significant factor. CONCLUSIONS: Electronic
      patient record system can be implemented in an urban ambulance service in such a
      way that documentation method does not become a significant factor in determining
      call duration in the long run. Temporary performance drop during the first 3
      months after introduction was noticed, reflecting adaptation process to a new way
      of working.

PMID- 19857414
TI  - The relationship between alcohol consumption and injury in ED trauma patients.
AB  - BACKGROUND: Alcohol-related injuries are significantly more serious than non
      alcohol-related injuries. However, there have been few data on the relationship
      between alcohol consumption and injury in the Korea. This study was designed to
      determine the absence or presence of alcohol consumption at the time of injury
      and the relationship between the quantity of alcohol and the extent of injury.
      MATERIALS AND METHODS: The study subjects consisted of trauma patients aged 15
      years or older with the emergency department admission at 5 emergency medical
      centers. With the informed consent, patients were screened using the
      questionnaire and blood alcohol concentration. The subjects were divided into 2
      groups according to the blood alcohol concentration level: the nonintoxicated and
      intoxicated groups. The demographic characteristics, cause of injury, injury
      severity, and length of hospitalization were compared between the 2 groups.
      RESULTS: Of a total of 407 cases, there were 123 cases in the intoxicated group
      and 284 cases in the nonintoxicated group. As to the severity of injury, an
      Abbreviated Injury Scale was significantly higher in the head and face. Injury
      Severity Score was higher in intoxicated group with marginal statistical
      significance. There was no significant difference in the total length of
      hospitalization, but the length of intensive care unit admission was
      significantly longer in the intoxicated group than in the nonintoxicated group.
      CONCLUSION: There may be no significant correlation between alcohol consumption
      and injury severity. However, injury severity may increase with increasing
      quantity of alcohol and be greater in head injuries.

PMID- 19857415
TI  - New classification and clinical characteristics of reexpansion pulmonary edema
      after treatment of spontaneous pneumothorax.
AB  - OBJECTIVE: Reexpansion pulmonary edema (REPE) is a rare yet sometimes fatal
      complication associated with the treatment of lung diseases such as pleural
      effusion, pneumothorax, and hemothorax. The current study summarizes our
      experience with REPE for a 3-year period. METHODS: We prospectively collected
      demographic and clinical data on consecutive patients presenting to an academic
      university-based emergency department with spontaneous pneumothorax that was
      treated with closed thoracostomy for a 3-year period. RESULTS: Eighty-four study
      patients were enrolled between December 2002 and September 2005. Reexpansion
      pulmonary edema developed in 25 of 84 (29.8% [95% confidence interval, 21.0
      40.2]) patients. Many cases of REPE were small and asymptomatic and only
      diagnosed on computed tomography of the chest. There was only one death (1.2%
      [95% confidence interval, A to B]). Reexpansion pulmonary edema was associated
      with patients with larger pneumothoraces without fibrotic changes and with
      patients with hypoxia and fibrotic changes. Classic REPE as seen on chest
      radiograph was 16 (19.0%) in 84 patients. Diffuse REPE as seen only on computed
      tomography and involved more than 1 lobe was 1 (1.2%) in 84 patients. Isolated
      REPE as seen only on computed tomography and limited to lesser than 1 lobe was 8
      (9.5%) in 84 patients. CONCLUSIONS: The rate of REPE after tube thoracostomy of
      spontaneous pneumothorax is greater than previously reported and often
      asymptomatic. The risk of developing REPE is greater with larger pneumothorax,
      especially in patients without fibrotic lung changes, and with hypoxia in
      patients with fibrotic changes.

PMID- 19857416
TI  - Validation of the Infectious Diseases Society of America/American Thoracic
      Society criteria to predict severe community-acquired pneumonia caused by
      Streptococcus pneumoniae.
AB  - BACKGROUND: Severe community-acquired pneumonia (CAP) is usually defined as
      pneumonia that requires intensive care unit (ICU) admission; the primary pathogen
      responsible for ICU admission is Streptococcus pneumoniae. In this study, the
      2007 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS)
      consensus criteria for ICU admission were compared with other severity scores in
      predicting ICU admission and mortality. METHODS: We retrospectively studied 158
      patients with pneumococcal CAP (1999-2003). Clinical and laboratory features at
      the emergency department were recorded and used to calculate the 2007 IDSA/ATS
      rule, the 2001 ATS rule, 2 modified 2007 IDSA/ATS rules, the Pneumonia Severity
      Index (PSI), and the CURB (confusion, urea, respiratory rate, blood pressure)
      score. The sensitivity, specificity, positive predictive value, and negative
      predictive value (NPV) were assessed for the various indices. We also determined
      the criteria that were independently predictive of ICU admission and of mortality
      in our population. RESULTS: The 2007 IDSA/ATS criteria performed as well as the
      2001 ATS rule in predicting ICU admission both demonstrated high sensitivity
      (90%) and NPV (97%). For the prediction of mortality, the best tool proved to be
      the PSI score (sensitivity, 95%; NPV, 99%). The variables associated with ICU
      admission in this patient population included tachypnea, confusion, Pao(2)/Fio(2)
      ratio of 250 or lower, and hypotension requiring fluid resuscitation. Mechanical
      ventilation and PSI class V were independently associated with mortality.
      CONCLUSIONS: This study confirms the usefulness of the new criteria in predicting
      severe CAP. The 2001 ATS criteria seem an attractive alternative because they are
      simple and as effective as the 2007 IDSA/ATS criteria.

PMID- 19857417
TI  - D-dimer in patients with suspected acute mesenteric ischemia.
AB  - OBJECTIVES: The aims of this study were to assess the diagnostic value of D-dimer
      in patients with suspected acute mesenteric ischemia (AMI) and to evaluate the
      correlation between D-dimer levels and the severity of bowel necrosis. METHODS: A
      prospective, noninterventional study of 67 patients with clinical suspicion of
      AMI was performed. Measurement of D-dimer levels was performed using a latex
      turbidimetric method. RESULTS: Acute mesenteric ischemia was diagnosed in 23
      patients (34.3%) and non-AMI in 44 patients (65.7%). Median D-dimer levels on
      admission were 6.24 microg fibrinogen equivalent units (FEU)/mL (range, 0.96
      53.48 microg FEU/mL) in patients with AMI and 3.45 microg FEU/mL (range, 0.50
      44.69 microg FEU/mL) in non-AMI patients (P = .064). D-dimer had poor
      discriminative value to differentiate the presence from the absence of AMI with
      an area under the receiver operating characteristic curve of 0.64 (95% confidence
      interval, 0.50-0.78). A serum D-dimer cutoff value of 1.0 microg FEU/mL had a
      sensitivity of 96%, a specificity of 18%, a positive likelihood ratio of 1.17,
      and a negative likelihood ratio of 0.24. Among patients with AMI verified at
      operation, 8 had resectable bowl necrosis and 9 had unresectable bowel necrosis.
      There was no difference in serum D-dimer levels between resectable and
      unresectable bowel necrosis (P = .665). CONCLUSIONS: Detection of serum D-dimer
      could not help to differentiate patient with AMI from those with non-AMI. We did
      not find a correlation between serum D-dimer levels and the severity of AMI.
      However, measurement of D-dimer levels can be of value for a small decrease in
      the likelihood of AMI, when the result is low.

PMID- 19857418
TI  - Endotracheal tube cuff pressures in patients intubated before transport.
AB  - INTRODUCTION: Prolonged endotracheal tube cuff pressures (ETTCPs) greater than 30
      cm H(2)O cause complications ranging from sore throat to rare cases of
      tracheoesophageal fistula. In a series of patients, we sought to determine the
      proportion of patients with overinflated cuffs and to determine whether
      overinflation was associated with demographics, diagnostic category, or intubator
      credentials. METHODS: Between July 2007 and April 2008, we measured cuff
      pressures on a convenience sample of patients drawn from 2 groups. The
      "helicopter group" had pressure measured before transport by a single aeromedical
      transport service. The "hospital group" had pressure measured upon arrival to 1
      of 2 emergency departments after being intubated before transport. RESULTS: Three
      hundred patients aged 4 to 92 years (median, 57) were studied: 59.7% were male;
      and diagnostic categories were neurologic (33.7%), trauma (32.7%), cardiac
      (12.7%), and general medical/surgical (21.0%). Intubation occurred 1 to 28 000
      minutes before ETTCP assessment (median, 60). Endotracheal tube cuff pressure was
      greater than 30 cm H(2)O in 64.7% and ranged from 10 to 180 (median, 40). Forty
      nine percent of patients had ETTCP greater than 40 cm H(2)O. There was no
      association between ETTCP and age group, sex, diagnostic category, ETT size, time
      between intubation and ETTCP assessment, or intubator credentials. CONCLUSIONS:
      The most compelling results of the study are the high rates of elevated ETTCPs.
      Furthermore, there were no clear risk factors for elevated ETTCP. Although the
      risk of elevated ETTCP in the prehospital to acute care time frame is unclear, it
      seems reasonable to measure ETTCP after intubation in all patients.

PMID- 19857419
TI  - Ethics, equipoise, and evidence: when should investigators decide to not test
      their hypothesis.
AB  - In an excellent investigation of endotracheal tube cuff pressure assessment,
      "Endotracheal Tube Cuff Pressures in Patients Intubated Prior to Transport,"
      Chapman et al measured endotracheal tube cuff pressure in patients who arrive at
      their emergency department after being intubated in the field. This, the first
      published American study of this type, presents clear and convincing evidence
      that patients who undergo endotracheal intubation before transport have
      endotracheal tube cuff pressures that exceed safe limits. Although a study of
      this type has not been conducted on patients who are endotracheally intubated by
      emergency medicine physicians within the confines of an emergency department, we
      pose the question to the academic and clinical emergency medicine community,
      "Should such a study be conducted?" Instead, should the evidence offered by
      Chapman et al, in addition to that of other publications, be enough to prompt
      emergency physicians to abandon the practice of endotracheal intubation without
      measurement and/or control of endotracheal tube cuff pressure? To adequately
      understand the complexity of such an apparently simple question, it is necessary
      to consider 2 concepts: equipoise and evidence. Our hope is that readers will
      acknowledge the study of Chapman et al as a strong piece of evidence indicating
      that patients who undergo endotracheal intubation without measurement of
      endotracheal tube cuff pressure very likely have a pressure that exceeds the safe
      range. We hope this study, in conjunction with the other available evidence, will
      prompt readers to adopt measurement of endotracheal tube cuff pressure as a
      routine.

PMID- 19857420
TI  - The role of continuous positive airway pressure in acute cardiogenic edema with
      preserved left ventricular systolic function.
AB  - OBJECTIVE: The objective of the study was to compare the effect of continuous
      positive airway pressure (CPAP) in patients with acute cardiogenic pulmonary
      edema (ACPE) with preserved or impaired left ventricular systolic function with
      regard to resolution time. METHODS: In a prospective, preliminary observational
      cohort study, 18 patients with preserved left ventricular systolic function
      (group A) and 18 patients with systolic heart dysfunction (group B) with ACPE
      underwent CPAP (10 cmH(2)0) through a face mask with standard medical therapy
      after a morphologic echocardiographic investigation shortly before CPAP. RESULTS:
      Resolution time did not differ significantly between the 2 groups of patients (64
      +/- 25 minutes in diastolic group vs 80 +/- 33 minutes in systolic group). One
      patient in preserved left ventricular systolic function group required
      endotracheal intubation (not statistically significant). No patient died during
      hospital stay. Arterial blood gases improved after a trial of CPAP in both groups
      of patients. CONCLUSIONS: The results of this preliminary study show that
      resolution time is not significantly different in patients with ACPE with
      preserved or impaired systolic function submitted to CPAP.

PMID- 19857421
TI  - The early elevation of interleukin 6 concentration in cerebrospinal fluid and
      delayed encephalopathy of carbon monoxide poisoning.
AB  - OBJECTIVE: This study was designed to investigate whether interleukin 6 (IL-6) in
      cerebrospinal fluid (CSF) in the early phase of carbon monoxide (CO) poisoning
      can be a predictive marker of delayed encephalopathy (DE). METHODS: Nine patients
      with CO poisoning were included in the study. Cerebrospinal fluid was sampled
      within 24 hours of the last exposure to CO, on hospital day 4, and once a week
      for at least 1 month to determine IL-6 and myelin basic protein concentrations.
      All patients were followed at least 3 months. RESULTS: Three patients
      demonstrated significant early IL-6 elevation in CSF, normal IL-6 level in CSF on
      day 4, and significant delayed myelin basic protein elevation in CSF. The 2
      patients with the highest early IL-6 elevation in CSF developed DE. Interleukin 6
      in serum was not related to DE. CONCLUSION: Interleukin 6 in CSF at the early
      phase of CO poisoning may be a predictive marker of DE.

PMID- 19857422
TI  - Delusions of parasitosis.
AB  - BACKGROUND: Delusions of parasitosis (DP) is a rare psychiatric disorder in which
      the patient has a firm belief that she or he is infected by parasites. Although
      it is a psychiatric disorder, these patients often present to an emergency
      physician because they are convinced that they have a severe skin problem.
      TREATMENT: Patients with DP often reject psychiatric referral. The diagnosis of
      DP can usually be made based on history alone. However, it is important that the
      patient does not have an organic skin disorder and that the delusion is not
      secondary to another mental or physical illness. The current treatments of choice
      are the antipsychotic medications risperidone and olanzapine. CONCLUSIONS: In our
      experience, patients with DP seen in the emergency department who are suspected
      of having this condition can be a challenging diagnostic and treatment problem
      because they usually do not have health insurance. Consequently, we find it
      difficult to get dermatologic and psychiatric consultation to treat their
      illness.

PMID- 19857423
TI  - Phentermine cardiovascular safety.

PMID- 19857424
TI  - Diagnosing Mallory-Weiss in the ED.

PMID- 19857425
TI  - CASH as a mnemonic for indications of sodium bicarbonate for sodium channel
      blocker intoxication.

PMID- 19857426
TI  - Long QT syndrome and torsades de pointes induced by acute sulpiride poisoning.
AB  - Sulpiride, a selective dopamine D2 antagonist and a substituted benzamide
      derivative, is considered a safe antipsychotic and antidepressant agent with few
      adverse effects on the cardiovascular system. Sulpiride-induced torsades de
      pointes is rare. We report a case of long QT syndrome and torsades de pointes
      induced by ingestion of 1.5 g of sulpiride. Ventricular arrhythmia was initially
      treated with amiodarone, without success. Eventually, lidocaine and magnesium
      sulfate successfully terminated the ventricular arrhythmia. The patient was
      discharged uneventfully after 3 days of hospitalization. This case illustrates
      the fact that acute sulpiride poisoning may lead to life-threatening ventricular
      arrhythmia. Early recognition followed by effective therapy is crucial. Intensive
      cardiac monitoring is recommended for sulpiride poisoning.

PMID- 19857427
TI  - Pragmatic classification of the causes of high D-dimer.
AB  - Venous thromboembolism (VTE) remains the most common preventable cause of in
      hospital death and D-dimer (DD) is one of the essential diagnostic tools for it.
      Each risk factor for VTE can raise DD and they are numerous: 24 listed in 2008
      European Guidelines. Acute coronary syndrome and stroke increase DD
      concentration, too. Thus, all three most important causes of cardiovascular death
      are capable of raising DD. Recent evidence suggests DD as a sensitive marker also
      for acute aortic dissection. Many other processes may raise DD concentration:
      atrial fibrillation, congestive heart failure, disseminated intravascular
      coagulation, etc. The adequate DD interpretation is additionally important due to
      the frequent usage of the test (probably millions of times a year in the world).
      Simple and concise classification is much easier to remember and such one is
      suggested.

PMID- 19857428
TI  - Extensive injury after use of a mechanical cardiopulmonary resuscitation device.
AB  - We report a case of a 49-year-old woman with a ruptured liver and spleen found at
      autopsy, which may have been related to the use of a mechanical cardiopulmonary
      resuscitation (CPR) device (AutoPulse, ZOLL Medical Corporation, Chelmsford,
      Mass). She was admitted because of an out-of-hospital resuscitation, and under
      the suspicion of a pulmonary embolism, a thrombolytic agent was administered.
      Despite prolonged continuation of mechanical CPR, she died of persistent
      asystole. The evidence for improved outcomes after the use of a mechanical CPR
      device during resuscitation is still scarce. To prevent the unique complications
      reported here, regular checking of proper position of the chest band during
      resuscitation is advised.

PMID- 19857429
TI  - Children with lethal streptococcal fasciitis after a minor contusion injury.
AB  - Necrotizing fasciitis is a severe life-threatening soft tissue infection
      characterized by rapidly spreading necrosis of the fascia and the subcutaneous
      tissue. Mortality as a result of streptococcal necrotizing fasciitis has been
      associated with the presence of hypotension, streptococcal toxic shock syndrome,
      or bacteremia in the literature. These infections are rare in children, and the
      diagnosis should be considered in the presence of any soft tissue infection
      presenting with signs of toxicity and marked wound edema. In addition, traumatic
      compartment syndrome has also gained public attention. This condition is also
      potentially lethal if diagnosis and management are delayed, especially in
      patients with swollen limbs without fracture. A high index of suspicion is most
      important when there is a paucity of specific cutaneous findings early in the
      course of the disease. The diagnosis of necrotizing fasciitis should be
      considered for any individual who has unexplained limb pain. Even for treating
      patients with minor trauma, the emergency department physician should keep a high
      level of suspicion of the possibility of a fatal outcome from the subsequent
      invasive streptococcal infection.

PMID- 19857430
TI  - Haloperidol-induced neuroleptic malignant syndrome complicated by hyperosmolar
      hyperglycemic state.
AB  - Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency
      that may be caused by neuroleptic agents of any class. The association with
      hyperosmolar hyperglycemic state (HHS) is rare and carries a grave prognosis. We
      describe the case of a 25-year-old male patient with haloperidol-induced NMS
      complicated by HHS that culminated in the patient's death despite all treatment
      efforts. Physicians caring for diabetic psychiatric patients who are treated with
      neuroleptic agents should be aware of this association that may be prevented by
      tight glycemic control.

PMID- 19857431
TI  - Ruptured pheochromocytoma presents as acute myocardial infarction.
AB  - Pheochromocytomas are uncommon catecholamine-secreting tumors. The most common
      symptoms are of paroxysmal or sustained hypertension, or symptoms of paroxysmal
      adrenergic stimulation as palpitation, headache, and diaphoresis. The diversity
      of presentation often delays the diagnosis and is sometimes with catastrophic
      outcome. It had not been reported that acute myocardial infarction is a
      complication of ruptured pheochromocytoma. We describe a case with emergency
      department presented as acute myocardial infarction initially. On the following
      day, sudden drop of blood pressure and syncope attacked him. Coronary angiography
      revealed noncritical obstruction on proximal left anterior descending artery.
      After angioplasty, the patient still experienced episodes of hemodynamic
      collapse, and left flank pain developed. Abdominal computer tomogram demonstrated
      a large left adrenal tumor with fluid accumulation. Finally, the patient
      underwent surgical treatment and pathology confirmed the diagnosis.

PMID- 19857432
TI  - Hoarseness as a first manifestation of aortotracheal fistula.
AB  - Aortotracheal fistula is uncommon but invariably fatal if not diagnosed early and
      accurately. Most fistulas are related to aneurysm of the thoracic aorta. Massive
      hemoptysis is reported to occur in more than half of the patients and is often
      the final event. We report a patient with hoarseness as an initial manifestation
      due to the painless formation of a pseudoaneurysm of aortic arch, which soon
      ruptured. Bronchoscopy disclosed a tracheal bulging mass with surface
      irregularity on the distal end of trachea before massive hemoptysis. We thought,
      faced with the cardiovocal syndrome accompanied with hemoptysis, lethal
      aortopulmonary fistula should be highly suspected.

PMID- 19857433
TI  - False-positive urine pregnancy test in a woman with adenomysosis.
AB  - We present a case of a 39-year-old woman presenting to the emergency department
      with persistent vaginal bleeding with myoma and endometrium thickness. The
      qualitative urine human chorionic gonadotropin (hCG) showed positive result,
      however, the quantitative serum hCG had negative result. The negative serum hCG
      result suggests that the false-positive result was not caused by elevated
      circulating hCG. According to the urine hCG one-step pregnancy device, 1 mg/dL of
      hemoglobin may not interference the pregnancy result. Nevertheless, we found that
      the hemoglobin level was 40 mg/dL in the urine specimen. We designed a in vitro
      experiment to evaluate the effects of hemoglobin on urine pregnancy test. The
      concentrations of hemoglobin from 5 to 500 mg/dL did not yield a positive urine
      pregnancy test. On the basis of our findings, the false positive pregnancy test
      was not caused by hemoglobin. It is important to confirm a suspected false
      positive urine hCG test using a quantitative serum hCG test. Although it is not
      certain the mechanism for false positive reaction in this peculiar sample, the
      ACON urine hCG one-step pregnancy will occasionally yield a false-positive result
      in this class of patients.

PMID- 19857434
TI  - Prehospital mechanical ventilation of a critical cardiac tamponade.
AB  - Mechanical ventilation of a critical cardiac tamponade is a high-risk situation
      that can lead to asystolic cardiac arrest. We report a prehospital mechanical
      ventilation of a penetrating cardiac injury complicated with tamponade. Onset
      diagnosis of the circulatory arrest allowed by prehospital continuous
      ultrasonography led to earlier initiation of the resuscitation and might have
      favored successful outcome. Electrocardiographic signs are too late to diagnose
      circulatory arrest.

PMID- 19857435
TI  - Multiple pulmonary arteriovenous malformations presenting as an acute myocardial
      infarction.
AB  - Pulmonary arteriovenous malformations are rare, mostly asymptomatic vascular
      anomalies. These malformations cause direct right to left shunting of
      unoxygenated blood, resulting chronically in cyanosis, dyspnea, and exercise
      intolerance. The serious complications reported earlier have mainly been
      neurologic, for example, cerebrovascular accidents and brain abscesses and are
      most likely caused by paradoxical embolism. Detection of pulmonary arteriovenous
      malformations is challenging, and the emergency department personnel play an
      essential role. Once suspected, the diagnosis can be made promptly using standard
      imaging techniques and appropriate treatment may prevent serious complications.
      In this report, we describe a case of a 41-year-old man with acute anterior
      myocardial infarction, unexpectedly caused by emboli from pulmonary arteriovenous
      malformations. This rare etiology of acute myocardial infarction should be taken
      into consideration especially in cases with atypical presentation.

PMID- 19857436
TI  - Severe angioedema in myxedema coma: a difficult airway in a rare endocrine
      emergency.
AB  - Myxedema coma is the most lethal manifestation of hypothyroidism. It is a true
      medical emergency and can result in profound hemodynamic instability and airway
      compromise. Myxedema coma currently remains a diagnostic challenge due to the
      rarity of cases seen today, and failure to promptly initiate therapy with
      replacement thyroid hormone can be fatal. As thyroid hormone therapy can take
      days or weeks to reverse the manifestations of myxedema coma, interim supportive
      therapy is critical while awaiting clinical improvement. Some patients will
      require endotracheal intubation in the emergency department (ED), and physicians
      should be aware that unanticipated posterior pharyngeal edema in myxedema coma
      could severely complicate airway management. Although mechanical ventilation is a
      well-described adjunctive therapy for myxedema coma, reports of the potential
      difficulty in securing a definitive airway in these patients are rare. We
      describe a case of an unidentified woman who presented to the ED with myxedema
      coma requiring urgent endotracheal intubation and was found to have extensive
      posterior pharyngeal angioedema inconsistent with her relatively benign external
      examination. This case highlights the typical features of myxedema coma and
      discusses our necessity for a rescue device in definitive endotracheal tube
      placement. Emergency physicians should anticipate a potentially difficult airway
      in all myxedema coma patients regardless of the degree of external facial edema
      present.

PMID- 19857437
TI  - Splenic infarction and abscess complicating infective endocarditis.
AB  - Acute abdominal pain is one of the most common conditions confronted in the
      emergency department. Clues related to splenic infarction may be obscured, and
      the diagnosis is quite challenging even for experienced physicians or surgeons.
      For every patient diagnosed with splenic infarction, a scrutiny on the possible
      source of emboli should be carried out. In addition, splenic abscess must be
      suspected in patients of splenic infarction, especially if the infectious signs
      persist despite appropriate treatment. Rapid diagnosis and treatment are
      essential as its course can prove fatal. Infective endocarditis is the most
      common condition predisposing a patient to splenic abscess. Indeed, splenic
      abscess or infarction may be a disease entity at different stages in patients of
      infective endocarditis due to septic emboli of the spleen. The treatment of
      choice has been antibiotics, splenectomy, and valve replacement surgery. Herein,
      we report a case of splenic abscess and infective endocarditis cured by
      antibiotic treatment without the aid of drainage or surgery.

PMID- 19857438
TI  - Myocardial infarction, acute ischemic stroke, and hyperglycemia triggered by
      acute chlorine gas inhalation.
AB  - Chlorine is one of the most common substances involved in toxic inhalation. Until
      now, several accidental exposures have been reported. The damage to the
      respiratory tract in the immediate phase after exposure to chlorine is well
      defined. Death occurs particularly due to pulmonary edema with respiratory
      failure and circulatory collapse. On the other hand, no association with
      myocardial infarction, acute stroke, severe hyperglycemia, and acute chlorine
      inhalation has been reported in literature. In the present study, an elderly (74
      year-old) and diabetic case with myocardial infarction, acute stroke,
      hyperglycemia, and respiratory failure associated with acute chlorine
      intoxication after a diagnosis of acute chlorine poisoning and treatment in the
      emergency department is reported and the literature is revisited. Physicians
      should know that in elderly patients with a systemic disease who apply with
      chlorine gas inhalation, more serious complications along with damage in
      respiratory tract might be observed.

PMID- 19857439
TI  - Movement disorder caused by abuse of veterinary anesthesia containing tiletamine.
AB  - Zoletil (Telazol) is a fixed-ratio combination of the tranquilizer zolazepam,
      with the dissociative anesthetic tiletamine, used for injection anesthesia in
      dogs, cats, wild, and zoo animals. We report a veterinarian who developed
      movement disorder after abuse of Zoletil for a 2-week period. Phencyclidine
      derivatives, that is, tiletamine can induce movement disorder in human.
      Tiletamine/zolazepam can be abused for recreational purpose, especially by those
      people with easy access to veterinary medications. Emergency physicians should
      have high alert to the diverse presentations of drug abuse. This case again
      highlights that the association between accessibility of scheduled drugs and
      health care professionals.

PMID- 19857440
TI  - Cervical epidural hematoma after chiropractic spinal manipulation.
AB  - Spinal epidural hematoma is a rare but potentially devastating complication of
      spinal manipulation therapy. This is a case report of a healthy pregnant female
      who presented to the emergency department with a cervical epidural hematoma
      resulting from chiropractic spinal manipulation therapy that responded to
      conservative treatment rather than the more common route of surgical management.

PMID- 19857441
TI  - Acute appendicitis presenting with Klebsiella pneumoniae septicemia due to
      bacterial translocation.
AB  - Bacterial translocation (BT) is defined as the passage of viable bacteria from
      the gastrointestinal tract, across the intestinal wall, to the mesenteric lymph
      nodes or other extranodal sites and bloodstream. It has been shown in both animal
      and human studies and has been implicated as a source of sepsis in susceptible
      patients. Herein, a rare case of acute appendicitis in a nonimmunocompromised
      patient who presented with manifestations of Klebsiella pneumoniae septicemia, is
      described. Translocation of Klebsiella pneumoniae through the compromised
      appendix mucosa leading in dissemination of the infection into the bloodstream
      was likely the main causative factor for the atypical and toxic presentation of
      acute appendicitis. Thorough clinical investigation ruled out other sources of
      infection. Emergency physicians should be aware that septicemia may be the
      dominant presentation of acute appendicitis, due to dissemination of the
      infection into the bloodstream, secondary to bacterial translocation.

PMID- 19857442
TI  - Transdiaphragmatic repositioning of the heart in the setting of emergency
      laparotomy after blunt trauma.
AB  - Cardiac luxation after blunt trauma is a rare condition that carries a high
      mortality rate. We report a case of a left pericardial rupture with partial
      dislocation of the heart into the left pleural cavity and cardiac strangulation
      in a polytraumatized patient after a severe motor vehicle accident. This case is
      of special interest because the patient not only had cardiovascular compromise
      but was also actually in cardiac arrest and being resuscitated when an emergency
      repositioning of the heart through the diaphragm in the setting of damage control
      laparotomy restored circulation. This report stresses the need for a high index
      of suspicion for accurate early diagnosis of pericardial rupture.

PMID- 19857443
TI  - Unusual presentation of acute coronary syndrome. Bilateral coronary dissection
      after car accident.
AB  - Dissection of large and small vessels can be caused by deceleration trauma.
      Management of dissections is often difficult technically, and invasive
      interventions are associated with complications. We report the case of a 45-year
      old woman admitted with acute coronary syndrome after a car accident and
      deceleration trauma. The coronary angiogram showed a focal stenotic dissection of
      the left main and a long nonstenotic dissection of the right coronary artery.
      Aortography was normal. After a complicated but finally successful angioplasty,
      the patient developed an abdominal hemorrhagic complication due to her previous
      trauma, which required urgent laparotomy; spleen was then removed and laceration
      on liver surface was surgically repaired. The patient developed a severe
      coagulopathy after surgery, which led to an irreversible stage and death within
      24 hours.

PMID- 19857444
TI  - Pulmonary hypertension in a patient with Schmidt syndrome.
AB  - We describe a 26-year-old patient with long-standing autoimmune hypothyroidism.
      She was doing well until she developed Addisonian crisis accompanied by severe
      metabolic acidosis, hypoglycemia, hypomagnesemia, and hypokalemia. Subsequently
      she developed a life-threatening cardiac arrhythmia due to QT prolongation
      secondary to electrolyte imbalance. The association of autoimmune hypothyroidism
      and adrenal insufficiency in our patient suggests the diagnosis of autoimmune
      polyglandular syndrome type II or Schmidt syndrome. An echocardiography that was
      performed detected pulmonary hypertension without apparent cardiac or lung
      pathology. The association of pulmonary hypertension and Schmidt syndrome is rare
      and may be explained by a generalized immune activation leading to pulmonary
      endothelial damage or dysfunction.

PMID- 19857445
TI  - Midgut volvulus as a delayed consequence of posttraumatic mesenteric pseudocyst.
AB  - Complicated midgut volvulus is a surgical emergency with high mortality rate if
      not treated promptly. Most of midgut volvulus in adults is a silent form of
      congenital midgut malrotation, but it also can be acquired from other medical
      conditions, such as adhesion bands, tumors, and mesenteric cysts. Posttraumatic
      mesenteric pseudocysts are rare entities, and the diagnosis tends to be delayed.
      In reviewing the medical literature, midgut volvulus as a delayed consequence of
      posttraumatic hemorrhagic mesenteric pseudocyst has never been reported before.
      Here, we report a 50-year-old female patient who had experienced blunt abdominal
      injury 3 months earlier and midgut volvulus that resulted from a delayed
      posttraumatic hemorrhagic pseudocyst. The patient was successfully treated with
      surgical intervention.

PMID- 19857446
TI  - Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for
      cytomegalovirus in CMV seronegative adult volunteers.
AB  - Development of a cytomegalovirus (CMV) vaccine is a priority. We evaluated a two
      component alphavirus replicon particle vaccine expressing CMV gB or a pp65/IE1
      fusion protein, previously shown to induce robust antibody and cellular immune
      responses in mice, in a randomized, double-blind Phase 1 clinical trial in CMV
      seronegative subjects. Forty subjects received a lower dose (LD) or higher dose
      (HD) of vaccine or placebo by intramuscular or subcutaneous injection at Weeks 0,
      8 and 24. The vaccine was well tolerated, with mild to moderate local
      reactogenicity, minimal systemic reactogenicity, and no clinically important
      changes in laboratory parameters. All vaccine recipients developed ex vivo,
      direct IFN-gamma ELISPOT responses to CMV antigens (maximal mean spot-forming
      cells per 10(6) PBMC in LD and HD groups of 348 and 504 for pp65, 83 and 113 for
      IE1, and 138 and 114 for gB), and neutralizing antibodies (maximal geometric mean
      titer 110 with LD and 218 with HD). Polyfunctional CD4(+) and CD8(+) T cell
      responses were detected by polychromatic flow cytometry. This alphavirus replicon
      particle vaccine was safe and induced neutralizing antibody and multifunctional T
      cell responses against three CMV antigens that are important targets for
      protective immunity.

PMID- 19857447
TI  - Immunogenicity and safety of IXIARO (IC51) in a Phase II study in healthy Indian
      children between 1 and 3 years of age.
AB  - For adults the standard administration of the Japanese encephalitis vaccine
      IXIARO is two injections of 6 microg in a 28-day interval. Immunogenicity and
      safety of 3 and 6 microg of IXIARO compared to JenceVac were investigated in 60
      healthy Indian children aged between 1 and 3 years. JE specific neutralizing
      antibodies were measured at baseline and 28 days after the first and second
      vaccination. On Day 56 SCR of the 3 and 6 microg IXIARO and the JenceVac group
      were 95.7%, 95.2% and 90.9%, respectively, and GMT were 201, 218 and 230,
      respectively, both without statistically significant difference between the three
      groups. Local and systemic tolerability were captured in a diary 7 days post
      vaccination. No apparent difference was seen in the safety profile between the
      vaccines. These first immunogenicity and safety data in children are promising
      and support the use of a 3 microg dose in children below the age of three for
      further development of IXIARO in the paediatric population.

PMID- 19857449
TI  - Heterologous prime boost vaccination with DNA and recombinant modified vaccinia
      virus Ankara protects IFNAR(-/-) mice against lethal bluetongue infection.
AB  - Recent recombinant DNA technology has provided novel approaches to develop marker
      and safe vaccines against bluetongue virus (BTV). To develop new vaccination
      strategies against BTV infection we have engineered naked DNAs and recombinant
      modified vaccinia virus Ankara (rMVA) expressing VP2, VP5 and VP7 proteins from
      BTV-4. IFNAR(-/-) mice inoculated with DNA/rMVA-VP2, -VP5, -VP7 in an
      heterologous prime boost vaccination strategy generated significant levels of
      neutralizing antibodies against BTV-4 and they were completely protected against
      BTV-4 challenge. Interestingly, VP2 and VP7 proteins expressed in the DNA/rMVA
      vaccines induced a specific BTV T-cell response that might contribute to the
      protection of IFNAR(-/-) mice against challenge with BTV-4. In addition,
      antibodies against VP2, VP5, and VP7, but not NS3 were detected in the sera of
      DNA/rMVA-VP2, -VP5, -VP7 immunized mice confirming the DIVA (differentiating
      infected from vaccinated animals) properties of this vaccine. Overall, our
      results show that the heterologous prime boost vaccination with DNA/rMVA
      expressing VP2, VP5, and VP7 proteins protects against BTV-4 infection.

PMID- 19857448
TI  - Evaluation of the safety and immunogenicity of Plasmodium falciparum apical
      membrane antigen 1, merozoite surface protein 1 or RTS,S vaccines with adjuvant
      system AS02A administered alone or concurrently in rhesus monkeys.
AB  - In an effort to broaden the immune response induced by the RTS,S/AS02(A),vaccine,
      we have evaluated the immunogenicity of the RTS,S antigen when combined with
      MSP1(42) and with AMA1, antigens derived from the asexual blood stage. The
      objectives of this study were (i) to determine whether MSP1(42) and AMA1 vaccines
      formulated with the AS02(A) Adjuvant System were safe and immunogenic in the
      rhesus monkey model; (ii) to investigate whether MSP1(42) or AMA1 induced immune
      interference to each other, or to RTS,S, when added singly or in combinations at
      a single injection site; (iii) in the event of immune interference, to determine
      if this could be reduced when antigens were administered at separate sites. We
      found that MSP1(42) and AMA1 were safe and immunogenic, eliciting antibodies, and
      Th1 and Th2 responses using IFN-gamma and IL-5 as markers. When malaria antigens
      were delivered together in one formulation, MSP1(42) and RTS,S reduced AMA1
      specific antibody responses as measured by ELISA however, only MSP1(42) lowered
      parasite growth inhibitory activity of anti-AMA1 antibodies as measured by in
      vitro growth inhibition assay. Unlike RTS,S, MSP1(42) significantly reduced AMA1
      IFN-gamma and IL-5 responses. MSP1(42) suppression of AMA1 IFN-gamma responses
      was not seen in animals receiving RTS,S+AMA1+MSP1(42) suggesting that RTS,S
      restored IFN-gamma responses. Conversely, AMA1 had no effect on MSP1(42) antibody
      and IFN-gamma and IL-5 responses. Neither AMA1 alone or combined with MSP1(42)
      affected RTS,S antibody or IFN-gamma and IL-5 responses. Immune interference by
      MSP1(42) on AMA1 antibody responses was also evident when AMA1, MSP1(42) and
      RTS,S were administered concurrently at separate sites. These results suggest
      that immune interference may be complex and should be considered for the design
      of multi-antigen, multi-stage vaccines against malaria.

PMID- 19857450
TI  - The adjuvant CLDC increases protection of a herpes simplex type 2 glycoprotein D
      vaccine in guinea pigs.
AB  - Herpes simplex virus (HSV) infections are common but there is no vaccine
      available. We evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant for
      an HSV gD2 vaccine and compared it to an MPL/Alum adjuvant in a guinea pig model
      of genital herpes. The addition of CLDC to the gD2 vaccine significantly
      decreased acute and recurrent disease and most importantly the number of days
      with recurrent virus shedding compared to gD2 alone. Reductions in these outcomes
      were also detected when gD2+CLDC was compared to gD2+MPL/Alum. When the vaccine
      and adjuvants were evaluated as therapeutic vaccines, they were ineffective. CLDC
      enhanced protection compared to MPL/Alum and is the first vaccine to reduce
      recurrent virus shedding, a key to decreasing the spread of HSV-2.

PMID- 19857451
TI  - Improving the expression of recombinant soluble HIV Envelope glycoproteins using
      pseudo-stable transient transfection.
AB  - The Envelope glycoprotein (Env) of the human immunodeficiency virus (HIV) is the
      target of neutralizing antibodies (NAbs). So far, HIV Env-derived immunogens have
      not been able to elicit broad neutralizing antibody responses against primary
      isolates. Identifying conditions that will permit the efficient production of
      different soluble HIV Env proteins will facilitate a high throughput comparative
      analysis of the immunogenicity of diverse Env constructs, potentially identifying
      Env forms that are more conducive to the elicitation of anti-HIV NAbs. Here we
      compared different cell types, transfection reagents, transfection conditions and
      different DNA expression vectors on soluble HIV Envelope expression levels. We
      identified optimal expression conditions and developed a protocol to streamline
      and maximize production of diverse HIV Env constructs. Using this optimized
      platform, milligram quantities of purified soluble HIV Env trimer can be
      routinely achieved in a rapid and cost-effective manner.

PMID- 19857452
TI  - A novel assay for influenza virus quantification using surface plasmon resonance.
AB  - Quantification of hemagglutinin (HA) by single-radial immuno diffusion (SRID) is
      the predominant method to ensure product potency in seasonal influenza vaccines.
      Here a new method for quantification of influenza virus using biosensor
      technology is presented. The method employs quantification of virus via an
      inhibition assay format using HA proteins for H1N1, H3N2 and B immobilized on a
      sensor chip. Initial results showed the assay to have higher sensitivity
      (detection range 0.5-10 microg/ml), higher precision and significantly lower
      analysis and hands on time compared with SRID.

PMID- 19857453
TI  - Evaluation of a commercial bovine viral diarrhea virus vaccine in nonpregnant
      female alpacas (Vicugna pacos).
AB  - Bovine viral diarrhea virus (BVDV) is an emerging pathogen in alpacas and many
      questions still persist regarding disease mechanisms and control strategies. The
      purpose of this study was to evaluate a commercial BVDV vaccine for safety and
      efficacy in alpacas. Five nonpregnant alpacas were vaccinated with a modified
      live BVDV vaccine and challenged 25 days post-immunization by nasal and ocular
      inoculation with a BVDV Type 1b strain isolated from a confirmed BVDV
      persistently infected alpaca. Two nonpregnant alpacas served as non-vaccinated
      controls and were similarly challenged. Results indicated that BVDV virus could
      not be detected from the vaccinated alpacas but was detected in the unvaccinated
      alpacas. Results suggest that administration of modified-live BVDV vaccine
      protected the alpacas in this study from experimental challenge and no adverse
      effects from the vaccine were observed.

PMID- 19857455
TI  - Subcutaneous inoculation of a whole virus particle vaccine prepared from a non
      pathogenic virus library induces protective immunity against H7N7 highly
      pathogenic avian influenza virus in cynomolgus macaques.
AB  - Development of H7N7 highly pathogenic avian influenza virus (HPAIV) vaccines is
      an urgent issue since human cases of infection with this subtype virus have been
      reported and most humans have no immunity against H7N7 viruses. We made an H7N7
      vaccine combining components from an influenza virus library of non-pathogenic
      type A influenza viruses. Antibody and T cell recall responses specific against
      the vaccine strain were elicited by subcutaneous inoculation with the whole virus
      particle vaccine with or without alum as an adjuvant in cynomolgus macaques. No
      significant difference was observed in magnitude of antibody responses between
      vaccination with alum and vaccination without alum, though vaccination with alum
      induced longer recall responses of CD8(+) T cells than did vaccination without
      alum. After challenge with a subtype of H7N7 HPAIV, the virus was detected in
      nasal swabs of unvaccinated macaques for 8 days but only for 1 day in the animals
      vaccinated either with or without alum, although the macaques vaccinated with
      alum showed elevated body temperature more briefly after infection. These
      findings demonstrated that this H7N7 HPAIV strain is pathogenic to macaques and
      that the vaccine conferred protective immunity to macaques against H7N7 HPAIV
      infection.

PMID- 19857454
TI  - A novel human parainfluenza virus type 1 (HPIV1) with separated P and C genes is
      useful for generating C gene mutants for evaluation as live-attenuated virus
      vaccine candidates.
AB  - A novel recombinant human parainfluenza virus type 1 (rHPIV1), rHPIV1-C+P, in
      which the overlapping open reading frames of the C and P genes were separated in
      order to introduce mutations into the C gene without affecting P, was generated.
      Infectious rHPIV1-C+P was readily recovered and replicated as efficiently as
      HPIV1 wild type (wt) in vitro and in African green monkeys (AGMs). rHPIV1-C+P
      expressed increased levels of C protein and, surprisingly, activated the type I
      IFN and apoptosis responses more strongly than HPIV1 wt. rHPIV1-C+P provided a
      useful backbone for recovering an attenuated P/C gene mutation (Delta 84-85),
      which was previously unrecoverable, likely due to detrimental effects of the
      deletion on the P protein. rHPIV1-C(Delta 84-85)+P and an additional mutant,
      rHPIV1-C(Delta 169-170)+P, were found to replicate to similar titers in vitro and
      to activate the type I IFN and apoptosis responses to a similar degree as rHPIV1
      C+P. rHPIV1-C(Delta 84-85)+P was found to be highly attenuated in AGMs, and all
      viruses were immunogenic and effective in protecting AGMs against challenge with
      HPIV1 wt. rHPIV1-C(Delta 84-85)+P will be investigated as a potential live
      attenuated vaccine candidate for HPIV1.

PMID- 19857456
TI  - Functional and conformational modulation of human cytochrome P450 1B1 by anionic
      phospholipids.
AB  - We investigated the interaction of human P450 1B1 (CYP1B1) with various
      phospholipid bilayers using the N-terminally deleted (Delta2-4)CYP1B1 and (Delta2
      26)CYP1B1 enzymes. Among anionic phospholipids, phosphatidic acid (PA) and
      cardiolipin specifically increased the catalytic activities, membrane binding
      affinities, and thermal stabilities of both CYP1B1 proteins when
      phosphatidylcholine matrix was gradually replaced with these anionic
      phospholipids. PA- or cardiolipin-dependent changes of CYP1B1 conformation were
      revealed by altered Trp fluorescence and CD spectra. However, both PA and
      cardiolipin exerted more significant effects with the (Delta2-4)CYP1B1 than the
      (Delta2-26)CYP1B1 implying the functional importance of N-terminal region for the
      interaction with the phospholipid membranes. In contrast, other anionic
      phospholipids such as phosphatidylserine and the neutral phospholipid
      phosphatidylethanolamine had no apparent effects on the catalytic activity or
      conformation of CYP1B1. These data suggest that the chemical and physical
      properties of membranes influenced by PA or cardiolipin composition are critical
      for the functional roles of CYP1B1.

PMID- 19857457
TI  - Structural characterization of a family of cytochromes c(7) involved in Fe(III)
      respiration by Geobacter sulfurreducens.
AB  - Periplasmic cytochromes c(7) are important in electron transfer pathway(s) in
      Fe(III) respiration by Geobacter sulfurreducens. The genome of G. sulfurreducens
      encodes a family of five 10-kDa, three-heme cytochromes c(7). The sequence
      identity between the five proteins (designated PpcA, PpcB, PpcC, PpcD, and PpcE)
      varies between 45% and 77%. Here, we report the high-resolution structures of
      PpcC, PpcD, and PpcE determined by X-ray diffraction. This new information made
      it possible to compare the sequences and structures of the entire family. The
      triheme cores are largely conserved but are not identical. We observed changes,
      due to different crystal packing, in the relative positions of the hemes between
      two molecules in the crystal. The overall protein fold of the cytochromes is
      similar. The structure of PpcD differs most from that of the other homologs,
      which is not obvious from the sequence comparisons of the family. Interestingly,
      PpcD is the only cytochrome c(7) within the family that has higher abundance when
      G. sulfurreducens is grown on insoluble Fe(III) oxide compared to ferric citrate.
      The structures have the highest degree of conservation around "heme IV"; the
      protein surface around this heme is positively charged in all of the proteins,
      and therefore all cytochromes c(7) could interact with similar molecules
      involving this region. The structures and surface characteristics of the proteins
      near the other two hemes, "heme I" and "heme III", differ within the family. The
      above observations suggest that each of the five cytochromes c(7) could interact
      with its own redox partner via an interface involving the regions of heme I
      and/or heme III; this provides a possible rationalization for the existence of
      five similar proteins in G. sulfurreducens.

PMID- 19857458
TI  - Solid-state NMR study of membrane interactions of the pore-forming cytolysin,
      equinatoxin II.
AB  - Equinatoxin II (EqtII) is a pore-forming protein from Actinia equina that lyses
      red blood cell and model membranes. Lysis is dependent on the presence of
      sphingomyelin (SM) and is greatest for vesicles composed of equimolar SM and
      phosphatidylcholine (PC). Since SM and cholesterol (Chol) interact strongly,
      forming domains or "rafts" in PC membranes, (31)P and (2)H solid-state NMR were
      used to investigate changes in the lipid order and bilayer morphology of
      multilamellar vesicles comprised of different ratios of
      dimyristoylphosphatidylcholine (DMPC), SM and Chol following addition of EqtII.
      The toxin affects the phase transition temperature of the lipid acyl chains,
      causes formation of small vesicle type structures with increasing temperature,
      and changes the T(2) relaxation time of the phospholipid headgroup, with a
      tendency to order the liquid disordered phases and disorder the more ordered
      lipid phases. The solid-state NMR results indicate that Chol stabilizes the DMPC
      bilayer in the presence of EqtII but leads to greater disruption when SM is in
      the bilayer. This supports the proposal that EqtII is more lytic when both SM and
      Chol are present as a consequence of the formation of domain boundaries between
      liquid ordered and disordered phases in lipid bilayers leading to membrane
      disruption.

PMID- 19857459
TI  - CaMKII uses GTP as a phosphate donor for both substrate and autophosphorylation.
AB  - The vast majority of serine/threonine protein kinases have a strong preference
      for ATP over GTP as a phosphate donor. CK2 (Casein kinase 2) is an exception to
      this rule and in this study we investigate whether calcium/calmodulin-dependent
      protein kinase II (CaMKII) has the same extended nucleotide range. Using the
      Drosophila enzyme, we have shown that CaMKII uses Mg(2+)GTP with a higher K(m)
      and V(max) compared to Mg(2+)ATP. Substitution of Mn(2+) for Mg(2+) resulted in a
      much lower K(m) for GTP, while nearly abolishing the ability of CaMKII to use
      ATP. These similar results were obtained with rat alphaCaMKII, showing the
      ability to use GTP to be a general property of CaMKII. The V(max) difference
      between Mg(2+)ATP and Mg(2+)GTP was found to be due to the fact that ADP is a
      potent inhibitor of phosphorylation, while GDP has modest effects. There were no
      differences found between sites autophosphorylated by ATP and GTP, either by
      partial proteolysis or mass spectrometry. Phosphorylation of fly head extract
      revealed that similar proteins are substrates for CaMKII whether using Mg(2+)ATP
      or Mg(2+)GTP. This new information confirms that CaMKII can use both ATP and GTP,
      and opens new avenues for the study of regulation of this kinase.

PMID- 19857460
TI  - Calyculin A-induced neurite retraction is critically dependent on actomyosin
      activation but not on polymerization state of microtubules.
AB  - Calyculin A (CL-A), a toxin isolated from the marine sponge Discodermia calyx, is
      a strong inhibitor of protein phosphatase 1 (PP1) and 2A (PP2A). Although CL-A is
      known to induce rapid neurite retraction in developing neurons, the cytoskeletal
      dynamics of this retraction have remained unclear. Here, we investigated the
      cytoskeletal dynamics during CL-A-induced neurite retraction in cultured rat
      hippocampal neurons, using fluorescence microscopy as well as polarized light
      microscopy, which can visualize the polymerization state of the cytoskeleton in
      living cells. We observed that MTs were bent while maintaining their
      polymerization state during the neurite retraction. In addition, we also found
      that CL-A still induced neurite retraction when MTs were depolymerized by
      nocodazole or stabilized by paclitaxel. These results imply a mechanism other
      than depolymerization of MTs for CL-A-induced neurite retraction. Our
      pharmacological studies showed that blebbistatin and cytochalasin D, an inhibitor
      of myosin II and a depolymerizer of actin, strongly inhibited CL-A-induced
      neurite retraction. Based on all these findings, we propose that CL-A generates
      strong contractile forces by actomyosin to induce rapid neurite retraction
      independently from MT depolymerization.

PMID- 19857461
TI  - Dynasore, a dynamin inhibitor, suppresses lamellipodia formation and cancer cell
      invasion by destabilizing actin filaments.
AB  - Dynamic remodeling of actin filaments are bases for a variety of cellular events
      including cell motility and cancer invasion, and the regulation of actin dynamics
      implies dynamin, well characterized endocytotic protein. Here we report that
      dynasore, a inhibitor of dynamin GTPase, potently destabilizes F-actin in vitro,
      and it severely inhibits the formation of pseudopodia and cancer cell invasion,
      both of which are supported by active F-actin formation. Dynasore rapidly
      disrupted F-actin formed in brain cytosol in vitro, and the dynasore's effect on
      F-actin was indirect. Dynasore significantly suppressed serum-induced
      lamellipodia formation in U2OS cell. Dynasore also destabilized F-actin in
      resting cells, which caused the retraction of the plasma membrane. A certain
      amount of dynamin 2 in U2OS cells localized along F-actin, and co-localized with
      cortactin, a physiological binding partner of dynamin and F-actin. However, these
      associations of dynamin were partially disrupted by dynasore treatment.
      Furthermore, invasion activity of H1080 cell, a lung cancer cell line, was
      suppressed by approximately 40% with dynasore treatment. These results strongly
      suggest that dynasore potently destabilizes F-actin, and the effect implies
      dynamin. Dynasore or its derivative would be suitable candidates as potent anti
      cancer drugs.

PMID- 19857462
TI  - Identification of a novel nuclear localization signal and speckle-targeting
      sequence of tuftelin-interacting protein 11, a splicing factor involved in
      spliceosome disassembly.
AB  - Tuftelin-interacting protein 11 (TFIP11) is a protein component of the
      spliceosome complex that promotes the release of the lariat-intron during late
      stage splicing through a direct recruitment and interaction with DHX15/PRP43.
      Expression of TFIP11 is essential for cell and organismal survival. TFIP11
      contains a G-patch domain, a signature motif of RNA-processing proteins that is
      responsible for TFIP11-DHX15 interactions. No other functional domains within
      TFIP11 have been described. TFIP11 is localized to distinct speckled regions
      within the cell nucleus, although excluded from the nucleolus. In this study
      sequential C-terminal deletions and mutational analyses have identified two novel
      protein elements in mouse TFIP11. The first domain covers amino acids 701-706
      (VKDKFN) and is an atypical nuclear localization signal (NLS). The second domain
      is contained within amino acids 711-735 and defines TFIP11's distinct speckled
      nuclear localization. The identification of a novel TFIP11 nuclear speckle
      targeting sequence (TFIP11-STS) suggests that this domain directly interacts with
      additional spliceosomal components. These data help define the mechanism of
      nuclear/nuclear speckle localization of the splicing factor TFIP11, with
      implications for it's function.

PMID- 19857463
TI  - Neuropilin-1 forms complexes with vascular endothelial growth factor receptor-2
      during megakaryocytic differentiation of UT-7/TPO cells.
AB  - We investigated whether the gene expression of vascular endothelial growth factor
      (VEGF) and its receptors (VEGFR and neuropilin-1 [NRP-1]) could be specifically
      regulated during the megakaryocytic differentiation of human thrombopoietin (TPO)
      dependent UT-7/TPO cells. Undifferentiated UT-7/TPO cells expressed a functional
      VEGFR-2, leading to VEGF binding and VEGF(165)-induced tyrosine phosphorylation,
      cell proliferation, and apoptosis inhibition. The megakaryocytic differentiation
      of UT-7/TPO cells on treatment with phorbol myristate acetate (PMA) was
      accompanied by a marked up-regulation of NRP-1 mRNA and protein expression and by
      an increase in VEGF-binding activity, which was mainly mediated by VEGFR-2.
      VEGF(165) promoted the formation of complexes containing NRP-1 and VEGFR-2 in
      undifferentiated UT-7/TPO cells in a dose-dependent manner. Unlike human
      umbilical vein endothelial cells, PMA-differentiated UT-7/TPO cells exhibited
      complex formation between NRP-1 and VEGFR-2 even in the absence of VEGF(165).
      These findings suggest that NRP-1-VEGFR-2-complex formation may contribute to
      effective cellular functions mediated by VEGF(165) in megakaryocytic cells.

PMID- 19857464
TI  - R-spondin1 is required for normal epithelial morphogenesis during mammary gland
      development.
AB  - The R-spondin (Rspo) proteins constitute a novel class of ligands that induce Wnt
      signalling. Rspo1 knockout XX mice were previously shown to be sex-reversed, but
      some remain sub-fertile. These last were unable to feed their pups for some
      unknown reason. Using these mice and transplanted mammary tissues from Rspo1(-/-)
      virgin mice in nude mice, we report that the lack of Rspo1 expression results in
      the absence of duct side-branching development and subsequent alveolar formation,
      explaining the above mentioned phenotype. Our data demonstrate that local
      epithelial Rspo1 signalling is required for normal development of the mammary
      gland.

PMID- 19857465
TI  - Neucrin is a novel neural-specific secreted antagonist to canonical Wnt
      signaling.
AB  - A gene encoding a novel secreted protein in mice and humans was identified, and
      named Neucrin. Mouse Neucrin consists of 343 amino acids with a cysteine-rich
      domain in its carboxyl terminal region. The positions of 10 cysteine residues in
      the cysteine-rich domain are similar to those of Dickkopfs (Dkks), secreted Wnt
      antagonists. However, whereas Dkks have two cysteine-rich domains, Neucrin has
      only one. Neucrin as well as Dkks bound to LDL receptor-related protein 6 and
      inhibited the stabilization of cytosolic beta-catenin, indicating that Neucrin is
      an antagonist of canonical Wnt signaling. Mouse Neucrin expression was not
      detected in any major tissues in the adult, but was detected in developing neural
      tissues, including the brain and spinal cord. The expression pattern of Neucrin
      is distinct from that of any Dkk. Neucrin is a unique secreted Wnt antagonist
      that is predominantly expressed in developing neural tissues.

PMID- 19857466
TI  - Intact AQP0 performs cell-to-cell adhesion.
AB  - Aquaporins (AQPs) constitute a major conduit for movement of water across plasma
      membranes. AQP0 is expressed in the fiber cells and is critical for lens
      transparency and homeostasis as mutations and knockout have resulted in dominant
      lens cataract. Several functions have been attributed for AQP0. In vitro and ex
      vivo experiments from several laboratories have confirmed the water permeability
      function of AQP0. However, this function seems paradoxical when the lens switches
      protein expression from AQP1 in the equatorial epithelial cells to 40 times less
      efficient AQP0 in the differentiating fiber cells. A possible explanation is AQP0
      may perform unique function/s besides being a water pore. Indirect evidences
      including those from structural studies indicate a cell-to-cell adhesion role for
      AQP0. However, there is a lack of experimental evidence directly demonstrating
      the cell-to-cell adhesion capability of AQP0. We studied the adhesion property of
      human intact AQP0 by expressing it in adhesion-deficient mouse fibroblast L-cells
      using a newly devised method as well as a traditional assay. Our results reveal
      that AQP0 indeed can perform cell-to-cell adhesion. AQP1, two alternate splice
      variants of AQP4 (AQP4-M1and AQP4-M23) and E-cadherin were also tested to
      validate the results. Cell-to-cell adhesion and cell aggregation properties of
      AQP0 expressing L-cells were less than those of the positive control L-cells
      expressing mouse E-cadherin and greater than those of AQP4-M23. AQP1 or AQP4-M1
      expressing cells did not show cell-to-cell adhesion or cell aggregation. To our
      knowledge, this is the first report validating the possible structural role of
      intact AQP0 as a cell-to-cell adhesion protein, using an in vitro expression
      system.

PMID- 19857467
TI  - Differential feeding behavior and neuronal responses to CCK in obesity-prone and 
      resistant rats.
AB  - Deficits in satiation signals are strongly suspected of accompanying obesity and
      contributing to its pathogenesis in both humans and rats. One such satiation
      signal is cholecystokinin (CCK), whose effects on food intake are diminished in
      animals adapted to a high fat diet. In this study, we tested the hypothesis that
      diet-induced obese prone (OP) rats exhibit altered feeding and vagal responses to
      systemic (IP) administration of CCK-8 compared to diet-induced obese resistant
      (OR) rats. We found that CCK (4.0 microg/kg) suppressed food intake significantly
      more in OP than OR rats. To determine whether enhanced suppression of feeding is
      accompanied by altered vagal sensory responsiveness, we examined dorsal hindbrain
      expression of Fos-like immunoreactivity (Fos-Li) following IP CCK injection in OP
      and OR rats. After 4.0 microg/kg CCK, there were significantly more Fos-positive
      nuclei in the NTS of OP compared to OR rats. Treatment with 8.0 microg/kg CCK
      resulted in no significant difference in food intake or in Fos-Li between OP and
      OR rats. Also, we found that OP rats were hyperphagic on a regular chow diet and
      gained more weight compared to OR rats. Finally OP rats had decreased relative
      fat pad mass compared to OR rats. Collectively, these results show that OP rats
      exhibit a different behavioral and vagal neuronal responses to CCK than OR rats.

PMID- 19857468
TI  - Aromatic l-amino acid decarboxylase expression profiling and isoform detection in
      the developing porcine brain.
AB  - Aromatic l-amino acid decarboxylase (AADC) enzymatic activity is essential for
      the biosynthesis of the serotonin and dopamine neurotransmitters, and AADC
      activity is functionally associated with a number of human neuronal disorders.
      Here we describe the molecular characterization of AADC from the pig. Pig AADC
      shows a high degree of similarity to human and rodent AADC at the cDNA and
      protein level. Exon position shuffling has exchanged the location of the stop
      codon in pig AADC to the last exon 15 instead for the exon 14 position in the
      human, the rat, and the mouse AADC. Several pig AADC isoforms were identified,
      including the also in human described extraneuronal and neuronal isoforms
      generated by alternative splicing and alternative promoter usage. The AADC
      expression in the developing pig brain is highly expressed in the basal ganglia
      and the brain stem regions, and also significantly expressed in the cortex, the
      hippocampus and the cerebellum. Moreover, we observe that both the neuronal and
      the extraneuronal AADC mRNA isoforms were present at early brain developmental
      stages in the brain stem and the basal ganglia. This presents the first evidence
      that the non-neuronal AADC isoform also is expressed in the brain. Together our
      results propose that the porcine model is useful for future functional
      delineations of the AADC gene at the molecular level.

PMID- 19857469
TI  - Neurodegeneration in thiamine deficient rats-A longitudinal MRI study.
AB  - Selective neurodegeneration accompanied by mitochondrial dysfunction
      characterizes neurodegenerative disorders such as Alzheimer's and Parkinson's
      diseases. Thiamine deficiency (TD) in rats is a model for the study of cellular
      and molecular mechanisms that lead to selective neuronal loss caused by chronic
      oxidative deficits. Neurodegeneration in TD-rats develops over a period of 12 to
      14 days and can be partially reversed by thiamine administration. The aim of this
      study was to characterize the in-vivo progression of neurodegeneration and the
      neuronal rescue processes in TD using T(2) magnetic resonance mapping and
      diffusion tensor imaging (DTI). Each rat was scanned prior to TD induction (day
      0), before the appearance of neurological symptoms (day 10), during the
      symptomatic stage (days 12 and 14) and during the recuperation period (days 31
      and 87). Time-dependent lesions were revealed mainly in the thalamus and the
      inferior colliculi. Early decrease in the fractional anisotropy (FA) was found on
      day 10 in the inferior colliculi and to a lesser degree in the thalamus, while
      the earliest detectable changes in the T(2) parameter occurred only on day 12. FA
      values in the thalamus remained significantly low after thiamine restoration,
      suggesting irreversible disarrangement and replacement of neuronal structures.
      While T(2) values in the frontal cortex demonstrated no lesions, FA values
      significantly increased on days 14 and 31. An enlargement of the lateral
      ventricles was observed and persevered during the recovery period. This
      longitudinal MRI study demonstrated that in TD MRI can detect neurodegeneration
      and neuronal recovery. DTI is more sensitive than T(2) mapping in the early
      detection of TD lesions.

PMID- 19857470
TI  - Neuroprotective effect of 4-hydroxybenzyl alcohol against transient focal
      cerebral ischemia via anti-apoptosis in rats.
AB  - 4-hydroxybenzyl alcohol (4-HBA), one of the major active phenolic constituents of
      Gastrodia elata Blume, a very important traditional Chinese medicinal herb, has
      been shown to be an effective agent against the central and peripheral nervous
      disorders. In this study, we attempted to explore the possible mechanisms
      underlying the neuroprotection against transient focal cerebral ischemia by 4
      HBA.4-HBA (25, 50 mg/kg) was given 30 min before focal ischemia in rats caused by
      middle cerebral artery occlusion (1 h of occlusion, 24 h of reperfusion). Under
      the treatment of 50 mg/kg 4-HBA, total (100.76+/-2.90 mm(3)), cortical (64.91+/
      1.46 mm(3)), and sub-cortical (38.77+/-2.78 mm(3)) infarct volumes were
      significantly decreased in comparison to ischemia-reperfusion values.
      Neurological evaluation and Nissl-staining of the 4-HBA group were improved
      significantly compared to the untreated ischemia group. TUNEL-positive cells were
      reduced significantly in 4-HBA treated group. Results of immunofluorescence
      staining analysis and Western immunoblot indicated that 4-HBA increased the
      expression of Bcl-2 and inhibited the activation of caspase-3 ultimately
      inhibiting apoptosis. These results suggested that 4-HBA ameliorated ischemic
      injury induced by transient focal cerebral ischemia in rats, and this
      neuroprotective effect may be partly related to attenuate apoptosis pathway.

PMID- 19857471
TI  - Basal forebrain integrity and cognitive memory profile in healthy aging.
AB  - Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are
      assumed to contribute to age-associated impairment of explicit memory. Both
      neurotransmitters also modulate attention, working memory, and processing speed.
      To date, in vivo evidence linking structural age-related changes in these
      neuromodulatory systems to dysfunction within or across these cognitive domains
      remains scarce. Using a factor analytical approach in a cross-sectional study
      including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30
      years) adults, we assessed the relationship between structural integrity-as
      measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral
      tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain
      (major origin of cortical cholinergic projections), frontal white matter (FWM),
      and hippocampus to neuropsychological and psychosocial scores. Basal forebrain
      MTR and FWM changes correlated with a factor combining verbal learning and memory
      and working memory and, as indicated by measures of diffusion, were most likely
      due to vascular pathology. These findings suggest that frontal white matter
      integrity and cholinergic neuromodulation provide clues as to why age-related
      cognitive decline is often correlated across cognitive domains.

PMID- 19857472
TI  - Temporal gene expression profile of the hippocampus following trace fear
      conditioning.
AB  - In this paper we report the results of gene expression profiling of C57Bl/6N mice
      hippocampus after trace fear conditioning (TFC), and the identification of genes
      regulated at early and late steps after conditioning. Several of the genes
      regulated at early steps following TFC appeared common to many training
      protocols. At later stages (2 and 6 h), most of the genes identified were
      different from those identified following other learning paradigms resulting in
      memory consolidation. At 6 h after training, few genes were upregulated in
      respect to the naive condition, suggesting that many gene products have
      eventually to be downregulated to achieve stable synapses modification and memory
      formation. In conclusion, the results presented highlight a number of genes whose
      expression is specifically modified in the mouse hippocampus following TFC and
      demonstrate the specificity associated to different forms of conditioning.

PMID- 19857473
TI  - Chemokine-like factor 1, a novel cytokine, induces nerve cell migration through
      the non-extracellular Ca2+-dependent tyrosine kinases pathway.
AB  - Chemokine-like factor 1 (CKLF1) is a newly cloned chemotactic cytokine. The roles
      of CKLF1 in the immune system and the respiratory system have been reported, but
      its function in the nervous system is still remaining unclear. We aimed to
      investigate the role of CKLF1 in the nerve cell migration and its regulatory
      mechanisms. By chemotaxis assays and wound-healing assays, CKLF1 stimulated the
      migration of SH-SY5Y cells dose-dependently. By immunofluorescence staining,
      CKLF1 induced actin polymerization. By western blotting, proline-rich tyrosine
      kinase 2 (PYK2) was phosphorylated at Tyr-402 in response to CKLF1 and this
      phosphorylation was apparently suppressed by phospholipase C-gamma inhibitor
      U73122, but not extracellular Ca(2+) chelator EGTA. Furthermore, after
      transfection of dominant-negative mutant PYK2 plasmid, the chemotaxis upon CKLF1
      was significantly attenuated in SH-SY5Y cells. Concluding, CKLF1 stimulates the
      migration of SH-SY5Y cells dose-dependently by activating non-extracellular
      Ca(2+)-dependent tyrosine kinases pathway and inducing actin polymerization.

PMID- 19857474
TI  - The World Health Organization (WHO) classification of tumors of the hematopoietic
      and lymphoid tissues: an overview with emphasis on the myeloid neoplasms.
AB  - The World Health Organization (WHO) classification of myeloid and lymphoid
      neoplasms utilizes morphology, immunophenotype, genetics and clinical features to
      define disease entities of clinical significance. It is a consensus
      classification in which a number of experts have agreed on the classification and
      diagnostic criteria. In general, the classification stratifies neoplasms
      according to their lineage (myeloid, lymphoid, histiocytic/dendritic) and
      distinguishes neoplasms of precursor cells from those comprised of functionally
      mature cells. Lymphoid neoplasms are derived from cells that frequently have
      features that recapitulate stages of normal B-, T-, and NK-cell differentiation
      and function, so to some extent they can be classified according to the
      corresponding normal counterpart, although additional features, such as genotype,
      clinical features and even location of the tumor figure into the final
      classification listing as well. Five major subgroups of myeloid neoplasms are
      recognized based mainly on their degree of maturation and biologic properties:
      myeloproliferative neoplasms (MPNs) which are comprised primarily of mature cells
      with effective proliferation; myeloid (and lymphoid) neoplasms with eosinophilia
      and abnormalities of PDGFRA, PDGFRB and FGFR1, defined largely by the finding of
      significant eosinophilia and specific genetic abnormalities;
      myelodysplastic/myeloproliferative neoplasms (MDS/MPN), comprised mainly of
      mature cells with both effective and ineffective proliferation of various
      lineages; myelodysplastic syndromes (MDS), in which immature and mature cells are
      found with abnormal, dysplastic and ineffective maturation, and acute myeloid
      leukemia (AML), comprised of precursor cells with impaired maturation. Genetic
      abnormalities play an important role as diagnostic criteria for further sub
      classification of some myeloid neoplasms, particularly of AML. Although therapy
      related MDS and AML (t-MDS/AML) often have genetic defects identical to those
      found in de novo AML and de novo MDS, they are classified separately from de novo
      AML and MDS in order to emphasize their unique clinical and biologic properties.

PMID- 19857475
TI  - Lipid domains and mechanical plasticity of Escherichia coli lipid monolayers.
AB  - Lipid monolayers can be laterally dilated under the action of the barriers in a
      Langmuir trough thus allowing for measurements of their mechanical response. We
      study the stress response of Escherichia coli polar lipid extract and POPC
      against oscillatory deformations stressed up to a 20% of the initial area. For E.
      coli monolayers a nonlinear regime described by a series of Fourier harmonics of
      the excitation mode is found beyond a critical strain (u(C) approximately 1%). In
      contrast, the mechanical response of POPC monolayers is found linear upon much
      larger deformations. For E. coli monolayers the stress-strain plot reflects
      stress softening (plastic-like) behaviour whilst POPC behaves as a linear elastic
      body. No viscous delay with respect to the applied strain is detected in both
      systems, as expected for high fluid materials. The presence of phase coexistence
      domains as lipid reservoirs to facilitate lateral diffusion is claimed as a
      plausible mechanism underlying the observed mechanical plasticity.

PMID- 19857476
TI  - Relationship between genetic polymorphisms of angiotensin-converting enzyme and
      methylenetetrahydrofolate reductase as risk factors for type 2 diabetes in
      Tunisian patients.
AB  - BACKGROUND/AIMS: The role of methylenetetrahydrofolate reductase (MTHFR) and
      angiotensin-converting enzyme (ACE) gene polymorphisms as being risk factors for
      diabetes is still controversial. The aim was to investigate the distribution of
      ACE and MTHFR genotypes as well as to evaluate the role of plasmatic total
      homocysteine levels (tHcy) and ACE activity in Tunisian patients with type 2
      diabetes mellitus (T2DM). DESIGN AND METHODS: 115 T2DM patients compared to 116
      healthy volunteers. RESULTS: The ACE I/D polymorphism was significantly
      associated with diabetes (p<0.0001). The DD genotype and D allele were more
      frequent in patients compared to control group [DD: OR=4.93; p<0.0001; 95 % CI:
      2.71-8.97; D: OR=3.08, 95% CI: 2.09-4.51 p<0.0001]. MTHFR allele and genotype
      frequencies did not differ between patients and controls. The susceptibility to
      diabetes in individuals with genotypes DD+vTT was 13.39 and in the individuals
      with DD+CT was 6.57 times that of the controls. However, individuals with
      genotypes ID+CC or II+CT have a protective effect against diabetes. The DD and TT
      genotypes were associated with significantly higher ACE activity and tHcy levels
      in diabetics. CONCLUSION: Our data suggest that ACE ID polymorphism may act
      synergistically with MTHFR C677T polymorphism to assess diabetes risk.

PMID- 19857477
TI  - Serum retinol-binding protein 4 (RBP4) and retinol in a cohort of borderline
      obese women with and without gestational diabetes.
AB  - OBJECTIVES: To evaluate whether serum RBP4 correlates with gestational diabetes
      mellitus (GDM) in a cohort of borderline obese (BMI>30) pregnant women. DESIGN
      AND METHODS: Serum RBP4 and retinol were measured in pregnant women with (n=12)
      and without (n=10) GDM. RESULTS: RBP4, retinol and RBP4:retinol molar ratio were
      not different between the groups and were not associated with markers of insulin
      resistance. CONCLUSIONS: GDM is not associated with RBP4 or retinol among
      borderline obese pregnant women.

PMID- 19857478
TI  - Thioflavin T fluorescence in human serum: correlations with vascular health and
      cardiovascular risk factors.
AB  - OBJECTIVES: Amyloid fibrils and amyloid-like structures are implicated in
      atherosclerosis via macrophage activation and inflammation. A common property of
      amyloid-like structures is their ability to induce thioflavin T (ThT)
      fluorescence. We measured ThT fluorescence in serum and related these levels to
      traditional cardiovascular risk factors and non-invasive measures of vascular
      dysfunction (elasticity). In addition, chemically modified serum components that
      contribute to serum ThT fluorescence were explored and identified. DESIGN,
      METHODS, AND RESULTS: Sera from 105 people, including 35 healthy subjects, and 70
      high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with
      systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT
      fluorescence. Although mean (+/-SD) ThT fluorescence did not differ significantly
      between groups (controls 0.97+/-0.26, RA 1.12+/-0.45, and SLE 0.74+/-0.23), the
      combined data set showed significant inverse correlation (p=0.046) between ThT
      fluorescence tertiles and small artery elasticity. Correlation was also found
      between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C
      reactive protein. Floatation fractionation of apoB containing lipoproteins showed
      that ThT reactivity in this fraction correlated with both serum oxidised-LDL and
      LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was
      associated with the non-apoB containing serum fraction, with the majority of ThT
      fluorescence associated with albumin. Incubation of purified albumin with glucose
      or with methylglyoxal induced ThT fluorescence, suggesting that glycated or
      chemical adducts of albumin contribute to the variation in ThT fluorescence of
      human serum. CONCLUSIONS: We propose that the detection of these adducts in serum
      using ThT fluorescence measurements may provide a marker for chemically modified
      protein structures that could assist the assessment of cardiovascular disease
      risk.

PMID- 19857480
TI  - Study of cryopreservation of articular chondrocytes using the Taguchi method.
AB  - This study evaluates the effect of control factors on cryopreservation of
      articular cartilage chondrocytes using the Taguchi method. Freeze-thaw
      experiments based on the L(8)(2(7)) two-level orthogonal array of the Taguchi
      method are conducted, and ANOVA (analysis of variables) is adopted to determine
      the statistically significant control factors that affect the viability of the
      cell. Results show that the type of cryoprotectant, freezing rate, thawing rate,
      and concentration of cryoprotectant (listed in the order of influence) are the
      statistically significant control factors that affect the post-thaw viability.
      The end temperature and durations of the first and second stages of freezing do
      not affect the post-thaw viability. Within the ranges of the control factors
      studied in this work, the optimal test condition is found to be a freezing rate
      of 0.61+/-0.03 degrees C/min, a thawing rate of 126.84+/-5.57 degrees C/min,
      Me(2)SO cryoprotectant, and a cryoprotectant concentration of 10% (v/v) for
      maximum cell viability. In addition, this study also explores the effect of
      cryopreservation on the expression of type II collagen using immunocytochemical
      staining and digital image processing. The results show that the ability of
      cryopreserved chondrocytes to express type II collagen is reduced within the
      first five days of monolayer culture.

PMID- 19857479
TI  - Current state of hypothermic machine perfusion preservation of organs: The
      clinical perspective.
AB  - This review focuses on the application of hypothermic perfusion technology as a
      topic of current interest with the potential to have a salutary impact on the
      mounting clinical challenges to improve the quantity and quality of donor organs
      and the outcome of transplantation. The ex vivo perfusion of donor organs on a
      machine prior to transplant, as opposed to static cold storage on ice, is not a
      new idea but is being re-visited because of the prospects of making available
      more and better organs for transplantation. The rationale for pursuing perfusion
      technology will be discussed in relation to emerging data on clinical outcomes
      and economic benefits for kidney transplantation. Reference will also be made to
      on-going research using other organs with special emphasis on the pancreas for
      both segmental pancreas and isolated islet transplantation. Anticipated and
      emerging benefits of hypothermic machine perfusion of organs are: (i) maintaining
      the patency of the vascular bed, (ii) providing nutrients and low demand oxygen
      to support reduced energy demands, (iii) removal of metabolic by-products and
      toxins, (iv) provision of access for administration of cytoprotective agents
      and/or immunomodulatory drugs, (v) increase of available assays for organ
      viability assessment and tissue matching, (vi) facilitation of a change from
      emergency to elective scheduled surgery with reduced costs and improved outcomes,
      (vii) improved clinical outcomes as demonstrated by reduced PNF and DGF
      parameters, (viii) improved stabilization or rescue of ECD kidneys or organs from
      NHBD that increase the size of the donor pool, (ix) significant economic benefit
      for the transplant centers and reduced health care costs, and (x) provision of a
      technology for ex vivo use of non-transplanted human organs for pharmaceutical
      development research.

PMID- 19857481
TI  - Cryopreservation of primate embryonic stem cells with chemically-defined solution
      without Me2SO.
AB  - Human embryonic stem (hES) cells are expected to be useful in the fields of
      regenerative medicine and tissue engineering due to their pluripotency.
      Therefore, it is necessary to establish highly efficient and reliable methods for
      the cryopreservation of hES cells. We have cryopreserved cynomolgus and human ES
      cells by the vitrification method, using a chemically-defined dimethyl sulfoxide
      (Me(2)SO)-free and serum-free medium composed of Euro-Collins solution as a base
      medium and 40% (v/v) ethylene glycol (EG) and 10% (w/v) polyethylene glycol (PEG)
      as cryoprotectants. When the vitrification and the cryoprotectants were combined,
      the recovery ratio of hES cells was 22.9+/-7.7%, compared to 0.4+/-0.2% when the
      conventional slow-freezing method was used. After the cryopreservation and
      thawing cycle, hES cells were easily cultured and expressed undifferentiated cell
      markers such as Nanog, Oct-4, SSEA-4, and alkaline phosphatase activity after
      several subculturing steps. We also found that the pluripotency of hES cells was
      maintained, as demonstrated by teratoma formation of ES cells transplanted into
      severe combined immunodeficient (SCID) mice. Thus, we conclude that we have
      successfully cryopreserved primate ES cells with high efficiency using a Me(2)SO
      free, chemically-defined medium.

PMID- 19857482
TI  - Physiology and cryosensitivity of coral endosymbiotic algae (Symbiodinium).
AB  - Coral throughout the world are under threat. To save coral via cryopreservation
      methods, the Symbiodinium algae that live within many coral cells must also be
      considered. Coral juvenile must often take up these important cells from their
      surrounding water and when adult coral bleach, they lose their endosymbiotic
      algae and will die if they are not regained. The focus of this paper was to
      understand some of the cryo-physiology of the endosymbiotic algae, Symbiodinium,
      living within three species of Hawaiian coral, Fungia scutaria, Porites compressa
      and Pocillopora damicornis in Kaneohe Bay, Hawaii. Although cryopreservation of
      algae is common, the successful cryopreservation of these important coral
      endosymbionts is not common, and these species are often maintained in live
      serial cultures within stock centers worldwide. Freshly-extracted Symbiodinium
      were exposed to cryobiologically appropriate physiological stresses and their
      viability assessed with a Pulse Amplitude Fluorometer. Stresses included
      sensitivity to chilling temperatures, osmotic stress, and toxic effects of
      various concentrations and types of cryoprotectants (i.e., dimethyl sulfoxide,
      propylene glycol, glycerol and methanol). To determine the water and
      cryoprotectant permeabilities of Symbiodinium, uptake of radio-labeled glycerol
      and heavy water (D(2)O) were measured. The three different Symbiodinium subtypes
      studied demonstrated remarkable similarities in their morphology, sensitivity to
      cryoprotectants and permeability characteristics; however, they differed greatly
      in their sensitivity to hypo- and hyposmotic challenges and sensitivity to
      chilling, suggesting that standard slow freezing cryopreservation may not work
      well for all Symbiodinium. An appendix describes our H(2)O:D(2)O water exchange
      experiments and compares the diffusionally determined permeability with the two
      parameter model osmotic permeability.

PMID- 19857483
TI  - Luteolin promotes long-term potentiation and improves cognitive functions in
      chronic cerebral hypoperfused rats.
AB  - Processes of synaptic plasticity, such as long-term potentiation (LTP), has been
      considered a cellular correlate of learning and memory and many neurological
      disorders accompanied by cognitive deficits exhibit abnormal synaptic function.
      This emerging concept is exemplified by Alzheimer's disease. Mounting evidence
      suggests that Alzheimer's disease begins with subtle alterations of hippocampal
      synaptic efficacy prior to frank neuronal degeneration, which make it critical to
      identify LTP enhancers to slow down or stop the progression of Alzheimer's
      disease. In this study, we found flavonoid luteolin could enhance basal synaptic
      transmission and facilitate the induction of LTP by high frequency stimulation in
      the dental gyrus of rat hippocampus. Furthermore, we investigated the effects of
      luteolin on chronic cerebral hypoperfusion-induced spatial learning dysfunction
      and LTP impairment in rat. The results showed chronic cerebral hypoperfusion
      produced by 2-vessel occlusion significantly impaired spatial learning and
      memory, and luteolin reversed the learning and memory deficit. 2-vessel occlusion
      resulted in dramatic inhibition of LTP formation in the hippocampus and luteolin
      significantly rescued the LTP impairment. These results demonstrate that luteolin
      not only directly modulates LTP formation, but also protects synapses from the
      detrimental effects of chronic cerebral hypoperfusion on LTP formation, which may
      contribute to the protective effects of luteolin on learning and memory. By
      immunoblotting, we found the effects of luteolin on LTP and memory may due to the
      activation of cAMP response element-binding protein (CREB). Therefore, flavonoid
      luteolin shows great potential as a novel treatment agent for protecting synaptic
      function and enhancing memory in neurodegenerative disorders.

PMID- 19857484
TI  - Anti-tumor activity of emodin against human chronic myelocytic leukemia K562 cell
      lines in vitro and in vivo.
AB  - Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), a natural anthraquinone
      derivative isolated from Rheum palmatum L, has been reported to exhibit anti
      cancer effect on several human cancers such as liver cancers and lung cancers.
      However, the molecular mechanisms of emodin-mediated tumor regression have not
      been fully defined. Our preliminary study showed that emodin had highly cytotoxic
      effect on human chronic myeloid leukemia K562 cell lines. This study was
      performed to investigate the anti-tumor effect of emodin in human K562 cell line
      in vitro and in vivo. The MTT data showed the inhibition on growth of K562 cells
      following emodin treatment. Flow cytometry showed that the cell cycle of K562
      cells was arrested in G(0)/G(1) phase. Through Western blot analysis, we found
      that the apoptosis-related protein Bcl-2 was decreased in a dose-dependent manner
      and the Bax was increased after emodin treatment. Moreover, activations of
      caspase-3, -8 and -9 were demonstrated in vitro and in vivo. The increased Bax
      concurrent with the decreased of Bcl-2 indicated that emodin treatment might
      result in apoptosis of K562 cells. The cell apoptosis was also directly
      demonstrated by Annexin V-FITC, and DNA fragmentation assay. Additionally, the
      tumoricidal effect of emodin was measured using a xenograft nude mice model. We
      found that, after inoculated with the K562 cells, the nude mice treated with
      emodin showed a significant decrease of tumor volume and tumor weight in
      comparison to the control. Emodin could cause the regression of tumor. Both in
      vitro and in vivo studies suggest that emodin can be developed as a promising
      anti-chronic myeloid leukemia drug.

PMID- 19857485
TI  - PPARalpha stimulation exerts a blood pressure lowering effect through different
      mechanisms in a time-dependent manner.
AB  - Peroxisome proliferator activated receptors (PPARs) are a family of nuclear
      receptors that, upon activation with selective ligands, work as transcription
      factors. Recently, these have been related with the cardiovascular system. Our
      aim was to study PPARalpha-stimulation and its effects on blood pressure in rats
      with aortic coarctation, and to explore the role of the antioxidant system. Male
      Wistar rats (250-280 g) were distributed into the following groups: 1) sham; 2)
      aortic coarctated-vehicle-treated (AoCo-V), and 3) AoCo-clofibrate (100mg/kg)
      treated (AoCo-C). Rats were treated for 1 or 21 days. Clofibrate lowered blood
      pressure in both 1- and 21-day treatments. Renal reactive oxygen species
      increased after 1 day in AoCo-V, while clofibrate prevented this effect.
      Superoxide dismutase (SOD)-1 expression increased 3.6-fold upon PPARalpha
      stimulation (1 day) and returned to normal values by day 21. SOD-1 activity
      increased slightly in response to clofibrate. Renal activity of catalase
      increased in AoCo-C (1 day) and returned to normal (21 days). eNOS expression was
      not modified acutely (1 day) but increased at 21 days of treatment with
      clofibrate. Angiotensin II AT(1)-receptor expression as well as angiotensin II
      decreased in clofibrate-treated rats, while angiotensin II AT(2)-receptor
      expression increased, in both treatment periods. Angiotensin-(1-7) increased at
      21 days. Our results suggest that in the early development of AoCo-induced
      hypertension, stimulation of PPARalpha increases the antioxidant defenses,
      leading to improvement in endothelial factors while in the sub-chronic phase (21
      days), eNOS and angiotensin II receptors appear to play major roles in
      controlling blood pressure.

PMID- 19857487
TI  - Nicotinamide alleviates indomethacin-induced gastric ulcers: a novel antiulcer
      agent.
AB  - Nicotinamide, a precursor of nicotinamide adenine dinucleotide (NAD(+)), is an
      essential nutrient for cell growth that participates in DNA repair and energy
      production. Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is
      an intricate process involving gastric mucus depletion, increased microvascular
      permeability, nitric oxide imbalance, as well as free radical production. The
      present study was conducted to test for the possible gastroprotective effect of
      nicotinamide utilizing an acute indomethacin-induced gastric ulcer model.
      Sucralfate possesses antiulcer/antioxidant properties; hence it was used as the
      reference drug. Indomethacin resulted in hemorrhagic mucosal lesions, increased
      microvascular permeability, and reduced the gastric mucosal contents of nitric
      oxide and mucus. Moreover, it produced an imbalance in the mucosal redox state as
      indicated by a decline of glutathione and glutathione peroxidase, which were
      associated with increased lipid peroxides. Comparable to sucralfate, nicotinamide
      markedly decreased the severity of indomethacin-induced gastric lesions and
      restored the levels of altered biochemical parameters. Gastroprotection afforded
      by nicotinamide is possibly mediated by conservation of gastric mucus, as well as
      nitric oxide contents, enhanced gastric microvascular permeability, and its
      antioxidant properties.

PMID- 19857486
TI  - Beta2-adrenoceptor stimulation inhibits advanced glycation end products-induced
      adhesion molecule expression and cytokine production in human peripheral blood
      mononuclear cells.
AB  - Cell-to-cell interaction through binding of intercellular adhesion molecule-1
      (ICAM-1) and CD40 on monocytes to their ligands on T-cells plays crucial roles in
      cytokine production. Advanced glycation end products (AGEs) subtypes induce
      complications in diabetes. In a previous study, we found that glyceraldehyde
      derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) at 100 microg/ml
      induced the expressions of ICAM-1 and CD40 on monocytes and the production of
      interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in human peripheral
      blood mononuclear cells. beta(2)-adrenoceptor stimulation has been demonstrated
      to modulate the production of inflammatory mediators. In the present study, we
      found that norepinephrine, epinephrine and isoproterenol inhibited AGE-2- and AGE
      3-induced adhesion expression and cytokine production in a concentration
      dependent manner. The action of these catecholamines was antagonized by beta(2)
      adrenoceptor antagonist, but not by alpha(1)-, alpha(2)- and beta(1)-adrenoceptor
      antagonist. beta(2)-adrenoceptor agonists, salbutanol and terbutaline inhibited
      AGE-2- and AGE-3-induced adhesion expression and cytokine production, but
      alpha(1)-, alpha(2)- and beta(1)-adrenoceptor agonist had no effect, indicating
      that the stimulation of beta(2)-adrenoceptor might improve AGEs-initiated
      complications in diabetes.

PMID- 19857488
TI  - Anti-inflammatory activity of hispidol A 25-methyl ether, a triterpenoid isolated
      from Ponciri Immaturus Fructus.
AB  - The anti-inflammatory activity of hispidol A 25-methyl ether (hispidol A 25-Me
      ether), a triterpenoid isolated from Ponciri Immaturus Fructus, was studied in
      lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. It was revealed
      that hispidol A 25-Me ether dose-dependently inhibits nitric oxide (NO)
      production by down-regulating inducible nitric oxide synthase (iNOS). It also
      reduces prostaglandin E(2) (PGE(2)) production by inhibiting cyclooxygenase-2
      (COX-2) expression proven on both mRNA as well as on protein levels. In addition,
      hispidol A 25-Me ether inhibits mRNA expressions of major pro-inflammatory
      cytokines including the tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta) and interleukin-6 (IL-6). Interestingly, hispidol A 25-Me ether
      probably exhibits a glucocorticoid-like activity, exerting functional inhibition
      of NF-kappaB without inhibition of DNA binging as de novo synthesis of IkappaB
      alpha was induced and thereby NF-kappaB activity was reduced. Furthermore,
      administrations of hispidol A 25-Me ether (1 and 10mg/kg, i.p., v/w.) were tested
      in two animal experiments involving acute inflammation, namely, the carrageenan
      induced paw edema swelling test and the acetic acid-induced vascular permeability
      assay, and showed concentration-related inhibitory activities. The anti
      inflammatory property of hispidol A 25-Me ether seems to resemble the effects of
      the class of naturally occurring anti-inflammatory agents, glucocorticoids, which
      inhibit transcriptions of important inflammatory mediators.

PMID- 19857489
TI  - Balamuthia mandrillaris: the multiple nuclei of Balamuthia amebas; their
      location, activity, and site of development.
AB  - Multiple nuclei were first noted in the pseudopodia of Balamuthia mandrillaris
      amebas feeding on mammalian cells. Phase microscope observations of live amebas
      in vitro reveal that while many amebas have a single nucleus, others have
      multiple nuclear-like structures, now confirmed as nuclei with hematoxylin and
      Feulgen stains. In the live cultures, two nuclei located near the tip of an
      extended pseudopodium were seen to fuse resulting in one larger morphologic unit.
      Such merging of nuclei has not been previously reported. Other nuclei were
      located at positions that subsequently became the site for the outgrowth of an
      additional pseudopod branch. A newly discovered large structure, a polyploid
      nucleus, was located in the mid-part of the ameba. Nucleoli of uniform size were
      seen to develop from the central mass of chromatin and each became surrounded by
      a vesicular component as they moved into the protoplasm as morphologically
      complete nuclei.

PMID- 19857490
TI  - Acanthamoeba spp.: in vitro effects of clinical isolates on murine macrophages,
      osteosarcoma and HeLa cells.
AB  - Three different cell lines (murine macrophages, HeLa and osteosarcoma cells) were
      assayed in order to check for the manifestation of the cytopathic effects of
      three strains of Acanthamoeba recently isolated in our laboratory from contact
      lens cases: CLC-16, CLC-41.r and CLC-51-l. Adhesion and cytotoxicity assays were
      carried out with these strains and the type strain Acanthamoeba castellanii Neff
      as a control. Briefly, the ability of these amoebae to bind to the three cell
      lines was calculated and supernatants were examined for cytotoxicity by measuring
      lactate dehydrogenase released as an estimate of cytotoxicity using a commercial
      detection kit. The three strains showed high adhesion and cytotoxicity levels
      when tested in the three cell lines. This study demonstrates the ability of these
      amoebae to degrade any of the tested cell lines. To the best of our knowledge,
      this is the first report of the in vitro effects of acanthamoebae on osteosarcoma
      cells.

PMID- 19857491
TI  - First report of a mixed infection due to Acanthamoeba genotype T3 and Vahlkampfia
      in a cosmetic soft contact lens wearer in Iran.
AB  - Acanthamoeba keratitis cases have emerged in the recent years in Iran. In this
      case, an amoebic keratitis due to a mixed infection with Acanthamoeba and
      Vahlkampfia species is reported. Corneal scrapes, contact lenses and contact lens
      cases obtained from the patient were analysed and were positive for cysts of
      Acanthamoeba and Vahlkampfia genera. Genus-specific PCR was carried out for both
      genera, confirming the microscopic observations. To our knowledge, this is the
      first reported case of a possible mixed amoebic infection due to Acanthamoeba and
      Vahlkampfia and raises awareness within contact lens wearers in Iran.

PMID- 19857492
TI  - Sarcoptes scabiei: Specific immune response to sarcoptic mange in the Iberian
      ibex Capra pyrenaica depends on previous exposure and sex.
AB  - Host acquired immunity is a critical factor that conditions the survival of
      parasites. Nevertheless, there is a shortage of data concerning inter-individual
      immunological inequalities in wild mammals. Sarcoptic mange is a widespread
      parasitosis that severely affects mammals such as the Iberian ibex (Capra
      pyrenaica). Despite some work on the subject, the immune response to sarcoptic
      mange infestation is still a complex and poorly understood phenomenon. To improve
      knowledge of the host-Sarcoptes immunological interaction, 18 Iberian ibexes were
      experimentally infested. IgG levels were assessed using ELISA to test for
      potential factors determining the specific immune response to infestation.
      Previous exposure and sex appeared to affect the IgG response to infestation and
      our results suggest a sex-biased immunomodulation. We discuss the immunological
      pattern of host-Sarcoptes interactions and also suggest further lines of work
      that may improve the understanding of immunological interactions of host
      Sarcoptes systems.

PMID- 19857493
TI  - Role of p53/FAK association and p53Ser46 phosphorylation in staurosporine
      mediated apoptosis: wild type versus mutant p53-R175H.
AB  - A novel survival role of focal adhesion kinase (FAK) that involves its nuclear
      translocation and direct association with p53 has been demonstrated. Here we
      examined the relationship between the p53/FAK interaction and Ser46
      phosphorylation of p53 (p-p53(Ser46)) in the apoptotic regulation of human
      esophageal squamous cell carcinoma (HOSCC) cell lines, expressing either wild
      type (wt) p53 or mutant (mt) p53-R175H. In contrast to the wt p53 cell lines, the
      mt p53-R175H cell line was resistant to staurosporine (STS)-mediated detachment
      and caspase-3 activation. Furthermore, despite the resistance of mt p53-R175H to
      Ser46 phosphorylation, both wt and mt HOSCC cells translocate FAK into the
      nucleus and maintain the p53/FAK interaction post STS treatment. These findings
      provide unique insight into how tumor cells harboring the R175H mutant may resist
      chemotherapeutic intervention.

PMID- 19857495
TI  - Gene structure, recombinant expression and functional characterization of grass
      carp leptin.
AB  - Leptin is an important hormone for the regulation of food intake, energy
      expenditure and reproduction in mammals, but information regarding its role in
      teleosts remains scant. In the present study, the gene structures of grass carp
      (Ctenopharyngodon idellus) and silver carp (Hypophthalmichthys molitrix) leptins
      were characterized. Recombinant grass carp leptin (rgc-LEP) was expressed in
      Escherichia coli and purified, and identified by mass spectrometric analysis. A
      strong anorexic effect on food intake was observed in grass carp on the first day
      after intraperitoneal (IP) injection of rgc-LEP, but not during the following
      days. Body weight of the leptin group (LEP group) and the pair-fed group (PF
      group) showed no difference throughout the experimental period. The acute and
      chronic effects on the expression of key genes correlating to food intake, energy
      expenditure, lipid metabolism and digestion were further characterized by real
      time PCR. Accordingly, the mRNA levels of neuropeptide Y (NPY), Stearoyl-CoA
      desaturase 1 (SCD1) and lipoprotein lipase (LPL) were significantly reduced
      whereas the mRNA levels of uncoupling protein 2 (UCP2), bile salt-activated
      lipase (BSAL) and fatty acid elongase (ELO) were significantly elevated on the
      first day after injection. No effect on the expression of these genes (except
      LPL) was observed on day 13. In contrast to the down-regulation by exogenous
      leptin in mammals, the mRNA level of grass carp leptin was elevated 5.76-fold on
      the first day after rgc-LEP treatment. Our results suggest that leptin has an
      acute effect on the regulation of food intake, energy expenditure and lipid
      metabolism in grass carp, but the effect can be rapidly counteracted through
      mechanisms that are currently unknown.

PMID- 19857496
TI  - Hybrid transgenic immune tolerant mouse model for assessing the breaking of B
      cell tolerance by human interferon beta.
AB  - To date, the therapeutic efficacy of recombinant human proteins is limited by
      their potential to break B cell tolerance in patients. The formation of
      neutralising antibodies (NABs) directed against recombinant human interferon beta
      (rhIFNbeta) is associated with a decrease in the therapeutic effect of the
      protein. For this reason, there is a need to study factors that can cause the
      immunogenicity of rhIFNbeta. Transgenic C57Bl/6 mice that are immune tolerant for
      human interferon beta (hIFNbeta) have been employed in a mouse model for
      assessing the breaking of immune tolerance by rhIFNbeta. In this study, we used
      the original C57Bl/6 mouse model as well as the hybrid offspring from crossings
      of transgenic C57Bl/6 mice with wildtype FVB/N mice to study the immunogenicity
      of three commercial rhIFNbeta products, Rebif, Avonex and Betaferon. As
      determined by ELISA, wildtype C57Bl/6 mice failed to form binding antibodies
      (BABs) against Rebif and Avonex formulated with human serum albumin. Because not
      all interferon beta products induce antibodies in wildtype C57Bl/6 mice, the
      transgenic C57Bl/6 mice cannot be used to study the breaking of tolerance by
      these products. However, the crossing of transgenic C57Bl/6 mice with FVB/N mice
      resulted in wildtype hybrid offspring in which all products were immunogenic and
      transgenic hybrid offspring that showed immune tolerance for hIFNbeta. Thus,
      these C57Bl/6 x FVB/N hybrid transgenic mice can be used to study the breaking of
      immune tolerance for all rhIFNbeta products. Of the three products, only
      Betaferon was able to break immune tolerance in the transgenic hybrids. With an
      MxA gene expression inhibition assay, NABs were detected in Betaferon treated
      wildtype hybrid mice, but not in transgenic hybrid mice, indicating a distinct
      immune mechanism in wildtype and transgenic mice. A pegylated rhIFNbeta-1a
      variant, PEG-rhIFNbeta-1a, induced antibodies in wildtype hybrid mice, but did
      not break the immune tolerance of transgenic hybrid mice. This suggests that
      pegylation did not affect the potential of rhIFNbeta-1a to break B cell
      tolerance.

PMID- 19857494
TI  - Sphingomyelin metabolism at the plasma membrane: implications for bioactive
      sphingolipids.
AB  - The plasma membrane (PM) is a major resource for production of bioactive lipids
      and contains a large proportion of the cellular sphingomyelin (SM) content.
      Consequently, the regulation of SM levels at the PM by enzymes such as
      sphingomyelinase (SMase) and SM synthase 2 (SMS2) can have profound effects -
      both on biophysical properties of the membrane, but also on cellular signaling.
      Over the past 20 years, there has been considerable research into the
      physiological and cellular functions associated with regulation of SM levels,
      notably with regards to the production of ceramide. In this review, we will
      summarize this research with particular focus on the SMases and SMS2. We will
      outline what biological functions are associated with SM metabolism/production at
      the PM, and discuss what we believe are major challenges that need to be
      addressed in future studies.

PMID- 19857497
TI  - Neurofilament ELISA validation.
AB  - BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for
      neuronal death and axonal degeneration. As these markers become more widely used,
      an inter-laboratory validation study is required to identify assay criteria for
      high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked
      immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was
      used to test the intra-assay and inter-laboratory coefficient of variation (CV)
      between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples.
      Critical factors, such as sample transport and storage, analytical delays,
      reaction temperature and time, the laboratories' accuracy and preparation of
      standards were documented and used for the statistical analyses. RESULTS: The
      intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results
      from the test laboratories correlated with those from the reference laboratory
      (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the
      correlation. Differences in the accuracy of standard preparation were identified
      as the most critical factor. Correcting for the error introduced by variation in
      the protein standards improved the correlation to R=0.98, p<0.0001 with an
      averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement
      was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1
      statistics. CONCLUSION: This multi-center validation study identified the lack of
      preparation of accurate and consistent protein standards as the main reason for a
      poor inter-laboratory CV. This issue is also relevant to other protein biomarkers
      based on this type of assay and will need to be solved in order to achieve an
      acceptable level of analytical accuracy. The raw data of this study is available
      online.

PMID- 19857498
TI  - Palmitate attenuates myocardial contractility through augmentation of
      repolarizing Kv currents.
AB  - There is considerable evidence to support a role for lipotoxicity in the
      development of diabetic cardiomyopathy, although the molecular links between
      enhanced saturated fatty acid uptake/metabolism and impaired cardiac function are
      poorly understood. In the present study, the effects of acute exposure to the
      saturated fatty acid, palmitate, on myocardial contractility and excitability
      were examined directly. Exposure of isolated (adult mouse) ventricular myocytes
      to palmitate, complexed to bovine serum albumin (palmitate:BSA) as in blood,
      rapidly reduced (by 54+/-4%) mean (+/-SEM) unloaded fractional cell shortening.
      The amplitudes of intracellular Ca(2+) transients decreased in parallel. Current
      clamp recordings revealed that exposure to palmitate:BSA markedly shortened
      action potential durations at 20%, 50%, and 90% repolarization. These effects
      were reversible and were occluded when the K(+) in the recording pipettes was
      replaced with Cs(+), suggesting a direct effect on repolarizing K(+) currents.
      Indeed, voltage-clamp recordings revealed that palmitate:BSA reversibly and
      selectively increased peak outward voltage-gated K(+) (Kv) current amplitudes by
      20+/-2%, whereas inwardly rectifying K(+) (Kir) currents and voltage-gated Ca(2+)
      currents were unaffected. Further analyses revealed that the individual Kv
      current components I(to,f), I(K,slow) and I(ss), were all increased (by 12+/-2%,
      37+/-4%, and 34+/-4%, respectively) in cells exposed to palmitate:BSA. Consistent
      with effects on both components of I(K,slow) (I(K,slow1) and I(K,slow)(2)) the
      magnitude of the palmitate-induced increase was attenuated in ventricular
      myocytes isolated from animals in which the Kv1.5 (I(K,slow)(1)) or the Kv2.1
      (I(K,slow)(2)) locus was disrupted and I(K,slow)(1) or I(K,slow2) is eliminated.
      Both the enhancement of I(K,slow) and the negative inotropic effect of
      palmitate:BSA were reduced in the presence of the Kv1.5 selective channel
      blocker, diphenyl phosphine oxide-1 (DPO-1).Taken together, these results suggest
      that elevations in circulating saturated free fatty acids, as occurs in diabetes,
      can directly augment repolarizing myocardial Kv currents and impair excitation
      contraction coupling.

PMID- 19857500
TI  - Structure, dynamics and thermodynamics of the human centrin 2/hSfi1 complex.
AB  - Centrin, an EF-hand calcium-binding protein, has been shown to be involved in the
      duplication of centrosomes, and Sfi1 (Suppressor of fermentation-induced loss of
      stress resistance protein 1) is one of its centrosomal targets. There are three
      isoforms of human centrin, but here we only considered centrin 2 (HsCen2). This
      protein has the ability to bind to any of the approximately 25 repeats of human
      Sfi1 (hSfi1) with more or less affinity. In this study, we mainly focused on the
      17th repeat (R17-hSfi1-20), which presents the highest level of similarity with a
      well-studied 17-residue peptide (P17-XPC) from human xeroderma pigmentosum
      complementation group C protein, another centrin target for DNA repair. The only
      known structure of HsCen2 was resolved in complex with P17-XPC. The 20-residue
      peptide R17-hSfi1-20 exhibits the motif L8L4W1, which is the reverse of the XPC
      motif, W1L4L8. Consequently, the dipole of the helix formed by this motif has a
      reverse orientation. We wished to ascertain the impact of this reversal on the
      structure, dynamics and affinity of centrin. To address this question, we
      determined the structure of C-HsCen2 [the C-terminal domain of HsCen2 (T94-Y172)]
      in complex with R17-hSfi1-20 and monitored its dynamics by NMR, after having
      verified that the N-terminal domain of HsCen2 does not interact with the peptide.
      The structure shows that the binding mode is similar to that of P17-XPC. However,
      we observed a 2 -A translation of the R17-hSfi1-20 helix along its axis, inducing
      less anchorage in the protein and the disruption of a hydrogen bond between a
      tryptophan residue in the peptide and a well-conserved nearby glutamate in C
      HsCen2. NMR dynamic studies of the complex strongly suggested the existence of an
      unusual calcium secondary binding mode in calcium-binding loop III, made possible
      by the uncommon residue composition of this loop. The secondary metal site is
      only populated at high calcium concentration and depends on the type of bound
      ligand.

PMID- 19857499
TI  - The crystal structure of the novobiocin biosynthetic enzyme NovP: the first
      representative structure for the TylF O-methyltransferase superfamily.
AB  - NovP is an S-adenosyl-l-methionine-dependent O-methyltransferase that catalyzes
      the penultimate step in the biosynthesis of the aminocoumarin antibiotic
      novobiocin. Specifically, it methylates at 4-OH of the noviose moiety, and the
      resultant methoxy group is important for the potency of the mature antibiotic:
      previous crystallographic studies have shown that this group interacts directly
      with the target enzyme DNA gyrase, which is a validated drug target. We have
      determined the high-resolution crystal structure of NovP from Streptomyces
      spheroides as a binary complex with its desmethylated cosubstrate S-adenosyl-l
      homocysteine. The structure displays a typical class I methyltransferase fold, in
      addition to motifs that are consistent with a divalent-metal-dependent mechanism.
      This is the first representative structure of a methyltransferase from the TylF
      superfamily, which includes a number of enzymes implicated in the biosynthesis of
      antibiotics and other therapeutics. The NovP structure reveals a number of
      distinctive structural features that, based on sequence conservation, are likely
      to be characteristic of the superfamily. These include a helical 'lid' region
      that gates access to the cosubstrate binding pocket and an active center that
      contains a 3-Asp putative metal binding site. A further conserved Asp likely acts
      as the general base that initiates the reaction by deprotonating the 4-OH group
      of the noviose unit. Using in silico docking, we have generated models of the
      enzyme-substrate complex that are consistent with the proposed mechanism.
      Furthermore, these models suggest that NovP is unlikely to tolerate significant
      modifications at the noviose moiety, but could show increasing substrate
      promiscuity as a function of the distance of the modification from the
      methylation site. These observations could inform future attempts to utilize NovP
      for methylating a range of glycosylated compounds.

PMID- 19857501
TI  - The steady-state phase distribution of the motor switch complex model of
      Halobacterium salinarum.
AB  - Steady-state analysis is performed on the kinetic model for the switch complex of
      the flagellar motor of Halobacterium salinarum (Nutsch et al.). The existence and
      uniqueness of a positive steady-state of the system is established and it is
      demonstrated why the steady-state is centered around the competent phase, a state
      of the motor in which it is able to respond to light stimuli. It is also
      demonstrated why the steady-state shifts to the refractory phase when the steady
      state value of the response regulator CheYP increases. This work is one aspect of
      modeling in systems biology wherein the mathematical properties of a model are
      established.

PMID- 19857502
TI  - Processing of fluorescence angiograms for the quantification of vascular effects
      induced by anti-angiogenic agents in the CAM model.
AB  - The chicken embryo chorioallantoic membrane (CAM) is widely used as an in vivo
      model to study the vascular effects of angiogenesis modulating agents. The main
      goal of the present study was to develop and validate a quantitative method to
      characterize time-dependent changes mainly in the capillary network of the CAM.
      To that end, the CAM capillaries were monitored in ovo, between days 7 and 13 of
      embryo development, using an epi-fluorescence microscope equipped with a
      sensitive camera following the intravenous injection of a fluorescent agent. We
      present a method by which the fluorescence angiograms of the CAM vasculature were
      recorded and analyzed by a multistep mathematical procedure to obtain a skeleton
      representation of the vessels and capillaries. From this skeleton descriptors
      were extracted, including the number of branching points/mm(2), the mean area of
      the vessel network meshes, and the mean of the 3rd quartile of the mesh area
      histogram. A qualitative visual assessment of the vasculature based on the number
      and the size of the avascular zones was obtained for comparison. To illustrate
      this approach, the activity of a neutralizing anti-vascular endothelial growth
      factor antibody, Avastin (Bevacizumab), was then quantified. Blood vessel growth
      inhibition and changes in the architecture of the capillary plexus after topical
      application of this drug on the CAM surface were monitored using the three
      descriptors mentioned above.

PMID- 19857503
TI  - Sex specific effect of prenatal testosterone on language lateralization in
      children.
AB  - Brain lateralization refers to the division of labour between the two hemispheres
      in controlling a wide array of functions and is remarkably well developed in
      humans. Based on sex differences in lateralization of handedness and language,
      several hypotheses have postulated an effect of prenatal exposure to testosterone
      on human lateralization development, the topic of a long-standing and unresolved
      debate. Here we demonstrate a clear relationship between prenatal levels of
      testosterone as assessed from amniotic fluid of healthy pregnant mothers and
      language lateralization of their offspring at the age of 6 years. Using focused
      attention conditions in the dichotic listening task, in which the child is
      instructed to report information from the left ear or the right ear, we were able
      to differentiate between potential effects of early testosterone on the left
      hemisphere and effects on inter-hemispheric connectivity. This provides a new
      method to distinguish between the claims of the different hypotheses. The results
      suggest that in girls higher prenatal testosterone exposure facilitates left
      hemisphere language processing, whereas in boys it reduces the information
      transfer via the corpus callosum.

PMID- 19857504
TI  - Male and female odors induce Fos expression in chemically defined neuronal
      population.
AB  - Olfactory information modulates innate and social behaviors in rodents and other
      species. Studies have shown that the medial nucleus of the amygdala (MEA) and the
      ventral premammillary nucleus (PMV) are recruited by conspecific odor
      stimulation. However, the chemical identity of these neurons is not determined.
      We exposed sexually inexperienced male rats to female or male odors and assessed
      Fos immunoreactivity (Fos-ir) in neurons expressing NADPH diaphorase activity
      (NADPHd, a nitric oxide synthase), neuropeptide urocortin 3, or glutamic acid
      decarboxylase mRNA (GAD-67, a GABA-synthesizing enzyme) in the MEA and PMV. Male
      and female odors elicited Fos-ir in the MEA and PMV neurons, but the number of
      Fos-immunoreactive neurons was higher following female odor exposure, in both
      nuclei. We found no difference in odor induced Fos-ir in the MEA and PMV
      comparing fed and fasted animals. In the MEA, NADPHd neurons colocalized Fos-ir
      only in response to female odors. In addition, urocortin 3 neurons comprise a
      distinct population and they do not express Fos-ir after conspecific odor
      stimulation. We found that 80% of neurons activated by male odors coexpressed GAD
      67 mRNA. Following female odor, 50% of Fos neurons coexpressed GAD-67 mRNA. The
      PMV expresses very little GAD-67, and virtually no colocalization with Fos was
      observed. We found intense NADPHd activity in PMV neurons, some of which
      coexpressed Fos-ir after exposure to both odors. The majority of the PMV neurons
      expressing NADPHd colocalized cocaine- and amphetamine-regulated transcript
      (CART). Our findings suggest that female and male odors engage distinct neuronal
      populations in the MEA, thereby inducing contextualized behavioral responses
      according to olfactory cues. In the PMV, NADPHd/CART neurons respond to male and
      female odors, suggesting a role in neuroendocrine regulation in response to
      olfactory cues.

PMID- 19857505
TI  - Conjugated and non-conjugated androgens differentially modulate specific early
      gene transcription in breast cancer in a cell-specific manner.
AB  - The role of androgen in breast cancer development is not fully understood,
      although androgen receptors (ARs) have been identified in breast cancer clinical
      samples and cell lines. However the whole spectrum of androgen actions cannot be
      accounted to the classic AR activation and the possible existence of a cell
      surface-AR has been suggested. Indeed, androgen, like all steroids, has been
      reported to trigger membrane-initiated signaling activity and exert specific
      actions, including ion channels and kinase signaling pathway activation,
      ultimately affecting gene expression. However, the molecular nature of membrane
      androgen sites represents another major persisting question. In the present
      study, we investigated early transcriptional effects of testosterone and the
      impermeable testosterone-BSA conjugate, in two breast cancer cell lines (T47D and
      MDA-MB-231), in an attempt to decipher specific genes modified in each case,
      providing evidences about specific membrane-initiating actions. Our data indicate
      that the two agents affect the expression of several genes. A group of genes were
      commonly affected while others were uniquely modified by each agent, including
      interaction with growth factors and K(+)-channels. In MDA-MB-231 cells, that are
      AR negative, the majority of genes affected by testosterone were also affected by
      testosterone-BSA indicating a membrane-initiated action. Subsequent analysis
      revealed that the two agents trigger different molecular pathways and
      cellular/molecular functions, suggestive of a molecular or functional
      heterogeneity of membrane and intracellular AR. In addition, the reported
      phenotypic interactions of membrane-acting androgen with growth factor were
      verified at the transcriptomic level, as well as their ion channel-modifying
      effects. Finally an interesting interplay between membrane-acting androgen with
      inflammation-related molecules, with potential clinical implications was
      revealed.

PMID- 19857506
TI  - Unusual oxidative transformations of a steroidal 16alpha,17alpha,22-triol.
AB  - A number of unexpected reactions were observed during attempts to invert
      configuration at C16 in 16alpha,17alpha,22-triol 3a. The PDC oxidation of 3a
      produced the D-seco-aldehyde 4a. Analogous compound 4b was obtained by Swern
      oxidation of the 16alpha,17alpha-dihydroxy-22-O-TES-ether 3b in addition to the
      desired 16-ketone 7. The unprotected triol 3a yielded pentacyclic products 5 and
      6 under similar conditions. The Mitsunobu reaction of the triol 3a afforded 16
      ketone 8 with inverted configuration of the side chain. During heating of a
      solution of 3a in THF with NaH at reflux autoxidation to the 16-ketone cyclic
      hemiketal 5, identical to one of the Swern oxidation products, took place.

PMID- 19857507
TI  - Inhibition of the myotoxic activities of three African Bitis venoms (B.
      rhinoceros, B. arietans and B. nasicornis) by a polyvalent antivenom.
AB  - A murine model of venom-induced myotoxicity was used to assess the antimyotoxic
      capacity of a polyvalent antivenom (PAV), rich in F(ab')2 fragments, obtained
      from horses immunized with Bitis venoms. Intramuscular (i.m.) injection of Bitis
      rhinoceros, Bitis arietans or Bitis nasicornis into mice induced a time- and dose
      dependent increase in plasma CK activity. The area under the plasma CK activity
      vs. time curve (AUC) between 0 and 48 h was used to quantify the data. Pre
      incubation with PAV neutralized the venoms' myotoxicity, in a concentration
      dependent manner: 80-100% neutralization occurred when the ratio of the PAV
      volume to the venom mass was 3-fold that recommended for use in human
      envenomation. Intravenous administration of PAV 1 h before the i.m. venom
      injection, afforded significant protection against myotoxicity, especially in the
      case of B. arietans. An antimyotoxic effect was also observed, albeit reduced,
      when the PAV treatment was applied 1 h after the venom injection. These data
      indicate that a PAV developed and manufactured in Brazil protects against the
      myotoxicity of the venoms of B. rhinoceros, B. arietans or B. nasicornis, which
      account for a large number of snakebite accidents in the African continent.

PMID- 19857508
TI  - Isolation and molecular cloning of venom peptides from Orancistrocerus drewseni
      (Hymenoptera: Eumenidae).
AB  - Three venom peptides (OdVP1, OdVP2 and OdVP3) were isolated from the venom of the
      solitary wasp Orancistrocerus drewseni (Hymenoptera: Eumenidae). The mature venom
      peptide sequences were determined via ESI-Q-TOF MS/MS and by searching the O.
      drewseni venom gland/sac-specific EST library. All of the OdVPs shared the
      typical characteristics of amidated C-termini proteins and contained a high
      content of hydrophobic and positively charged amino acids, suggesting that they
      adopt an amphipathic alpha-helical secondary structure, as is the case for
      mastoparan from Vespula lewisii. The cDNA sequence of the OdVP1 precursor was
      obtained by 5'- and 3'-rapid amplification of cDNA ends (RACE), and the OdVP2 and
      OdVP3 precursor transcripts were identified from the venom gland/sac-specific EST
      library. While the mature peptide sequences were distinct from one another, the
      overall transcript structure of the OdVPs showed a high homology to that of
      mastoparan-B from Vespa basalis in that they contained a signal sequence, a
      prosequence, a mature peptide and a C-terminal glycine. The OdVPs, particularly
      OdVP2 and OdVP2L (an analog of OdVP2), exhibited strong antifungal activities,
      but poor antibacterial activities. OdVP2L, which possessed additional Glu-Pro
      residues, did not have antimicrobial activity against bacteria or Gram-positive
      yeast but retained activity against Botrytis cinerea.

PMID- 19857509
TI  - Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis:
      a meta-analysis of randomized placebo-controlled trials.
AB  - OBJECTIVE: To estimate the efficacy and safety of diacerein as a pain-reducing
      agent in the treatment of osteoarthritis (OA), using meta-analysis of published
      randomized placebo-controlled trials (RCTs). METHODS: Systematic searches of the
      bibliographic databases Medline, Embase, Cinahl, Chemical Abstracts, Cochrane and
      Web of Science for RCTs concerning diacerein treatment of OA. INCLUSION CRITERIA:
      explicit statement about randomization to either diacerein or placebo, and co
      primary outcomes being reduction in pain and improvement in function. Efficacy
      effect size (ES) was estimated using Hedges's standardized mean difference.
      Safety was measured via the risk ratio (RR) of patients having at least one
      episode of diarrhoea, or withdrawal due to adverse events. Trials were combined
      by using random-effects meta-analysis. Consistency was evaluated via the I
      squared index. RESULTS: Six trials (seven sub-studies; 1533 patients) contributed
      to the meta-analysis, revealing a large degree of inconsistency among the trials
      (I(2)=56%) in regard to pain reduction: the combined ES was -0.24 [95% confidence
      intervals (CI): -0.39 to -0.08, P=0.003], favouring diacerein. The statistically
      significant improvement in function (P=0.01) was based on a small amount of
      heterogeneity (I(2)=11%), but presented a questionable clinical effect size (ES=
      0.14). Risk of publication bias could not be excluded, and trials with duration
      of more than 6 months did not favour diacerein. There was an increased risk of
      diarrhoea with diacerein (RR=3.51 [2.55-4.83], P<0.0001), and some withdrawal
      from therapy following adverse events (RR=1.58 [1.05-2.36], P=0.03). CONCLUSIONS:
      Diacerein may be an alternative therapy for OA for patients who cannot take
      paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) because of adverse
      effects or lack of benefit. However, it is associated with increased risk of
      diarrhoea, and the symptomatic benefit after 6 months remains unknown.

PMID- 19857511
TI  - The roles of RNA synthesis and protein translation during reconsolidation of
      passive-avoidance learning in the day-old chick.
AB  - This series of experiments investigated the role of protein translation and RNA
      synthesis on consolidation and reconsolidation of passive avoidance learning
      (PAL) in day-old chicks. Although it is well established that protein translation
      is required after a reminder, there are conflicting reports in the literature
      concerning the requirement for RNA synthesis at this time. Day-old male New
      HampshirexWhite Leghorn chicks were trained on a single trial passive avoidance
      task. The results confirmed the requirement for protein translation during
      reconsolidation with memory deficits induced by anisomycin (ANI) (10mg/kg)
      detected at 60min post-reminder. It was also established that RNA synthesis was
      required for consolidation of PAL through inhibition by 5,6-Dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB) (0.075microg/kg), administered at or after
      training. The same dose of DRB was also found to inhibit memory post
      reactivation. However injections were required before the reminder trial and
      memory deficits were evident by 60min, consistent with that found for ANI post
      reminder. As with ANI, the DRB-induced memory deficit post-reminder was also
      transient, and resolved by 24h post-reminder. For both reconsolidation drug
      studies, the memory deficit was wholly dependent on the memory being reactivated
      by a reminder-trial. The study highlights an important role for RNA synthesis
      following memory reactivation.

PMID- 19857510
TI  - Semi-automated segmentation to assess the lateral meniscus in normal and
      osteoarthritic knees.
AB  - OBJECTIVE: The goal of this study was to develop an algorithm to semi
      automatically segment the meniscus in a series of magnetic resonance (MR) images
      to use for normal knees and those with moderate osteoarthritis (OA). METHOD: The
      segmentation method was developed then evaluated on 10 baseline MR images
      obtained from subjects with no evidence, symptoms, or risk factors of knee (OA),
      and 14 from subjects with established knee OA enrolled in the Osteoarthritis
      Initiative (OAI). After manually choosing a seed point within the meniscus, a
      threshold level was calculated through a Gaussian fit model. Under anatomical,
      intensity, and range constraints, a threshold operation was completed followed by
      conditional dilation and post-processing. The post-processing operation
      reevaluates the pixels included and excluded in the area surrounding the meniscus
      to improve accuracy. The developed method was evaluated for both normal and
      degenerative menisci by comparing the segmentation algorithm results with manual
      segmentations from five human readers. RESULTS: The semi-automated segmentation
      method produces results similar to those of trained observers, with an average
      similarity index over 0.80 for normal participants and 0.75, 0.67, and 0.64 for
      participants with established knee OA with Osteoarthritis Research Society
      International (OARSI) joint space narrowing (JSN) scores of 0, one, and two
      respectively. CONCLUSION: The semi-automatic segmentation method produced
      accurate and consistent segmentations of the meniscus when compared to manual
      segmentations in the assessment of normal menisci in mild to moderate OA. Future
      studies will examine the change in volume, thickness, and intensity
      characteristics at different stages of OA.

PMID- 19857512
TI  - Antidepressant-like effect of low molecular proanthocyanidin in mice: involvement
      of monoaminergic system.
AB  - Proanthocyanidin is a phenolic product present in plants which has antioxidant,
      antinociceptive and neuroprotective properties, without inducing significant
      toxicological effects. The present study tested the hypothesis that low molecular
      proanthocyanidin from grapes that has optimized bioavailability, would exert
      antidepressant-like activities in behavioral despair tests. The results suggested
      that oral administration proanthocyanidin at doses of 25 and 50mg/kg for 7days
      significantly reduced the duration of immobility in both the tail suspension and
      forced swimming tests. The doses that affected the immobile response did not
      affect locomotor activity. In addition, the neurochemical and
      neuropharmacological assays showed that proanthocyanidin produced a marked
      increase of 5-HT levels at 25 and 50mg/kg in three brain regions, the frontal
      cortex, hippocampus and hypothalamus. Noradrenaline and dopamine levels were also
      increased when higher dose of proanthocyanidin (50mg/kg) administration both in
      the frontal cortex and hippocampus. These effects were similar to those observed
      for the classical antidepressant imipramine (10mg/kg, i.p.). Moreover, Our study
      suggested that proanthocyanidin (12.5, 25 and 50mg/kg) dose dependently inhibited
      monoamine oxidase-A (MAO-A) activity, while MAO-B inhibitory activity was also
      found at higher doses (25 and 50mg/kg) after 7days administration. MAO-A
      selective inhibitor, moclobemide (20mg/kg, i.g.) produced MAO-A inhibition of
      70.5% in the mouse brain. These findings suggest that the antidepressant-like
      effects of proanthocyanidin may involve the central monoaminergic
      neurotransmitter systems.

PMID- 19857513
TI  - Greenspace access, use, and physical activity: understanding the effects of area
      deprivation.
AB  - OBJECTIVES: To understand the patterning of greenspace provision and use by area
      deprivation, and determine how deprivation moderates relationships with physical
      activity. METHODS: The responses obtained from 6821 respondents to the 2005 'The
      Quality of Life in your Neighbourhood Survey' undertaken in Bristol, England,
      were combined with objective measures of access to greenspaces. Area deprivation
      was determined using the Index of Multiple Deprivation. Descriptive analyses
      examined how mean distance, perceived greenspace access and safety, visit
      frequency, and physical activity varied by deprivation quartile. Logistic
      regression models examined how relationships were moderated by deprivation.
      RESULTS: Respondents in more deprived areas lived closer to greenspaces, but
      reported poorer perceived accessibility, poorer safety, and less frequent use.
      Frequency of use declined with distance but only in the most affluent areas.
      Relationships between physical activity and perceived accessibility, safety, and
      visit frequency were moderated by deprivation. CONCLUSIONS: The accessibility of
      greenspaces was better in more deprived areas but those residents had more
      negative perceptions and were less likely to use the greenspaces. Interventions
      may be most effective if they target the perceptions and needs of residents of
      deprived neighbourhoods.

PMID- 19857514
TI  - Smoke-free laws and cigarette excise taxes in U.S. states with highest vs. lowest
      adult smoking rates in 2007.

PMID- 19857515
TI  - Standing up for the body. Recent progress in uncovering the networks involved in
      the perception of bodies and bodily expressions.
AB  - Recent studies of monkeys and humans have identified several brain regions that
      respond to bodies. Researchers have so far mainly addressed the same questions
      about bodies and bodily expressions that are already familiar from three decades
      of face and facial expression studies. Our present goal is to review behavioral,
      electrophysiological and neurofunctional studies on whole body and bodily
      expression perception against the background of what is known about face
      perception. We review all currently available evidence in more detail than done
      so far, but we also argue for a more theoretically motivated comparison of faces
      and bodies that reflects some broader concerns than only modularity or category
      specificity of faces or bodies.

PMID- 19857516
TI  - Social cognition in attention-deficit hyperactivity disorder (ADHD).
AB  - Attention-deficit hyperactivity disorder (ADHD) is associated with a range of
      cognitive deficits and social cognition impairments, which might be interpreted
      in the context of fronto-striatal dysfunction. So far only few studies have
      addressed the issue of social cognition deficits in ADHD. METHOD: Medline and
      Psyclit searches were performed for a 30-year period (1979-2009) using the words
      'ADHD' and 'social cognition', 'theory of mind', 'prosody', 'face perception',
      'humour' or 'social information processing'. Inclusion criteria consisted of a
      diagnosis according to DSM as well as the inclusion of a control group or a
      follow-up assessment following the treatment with methylphenidate. RESULTS: ADHD
      is clearly associated with social cognition impairments involving emotional face
      and prosody perception. Although the database is sparse so far, there is some
      evidence for theory of mind deficits and reduced empathy in ADHD. CONCLUSIONS: In
      summary, the social cognition impairments are consistent with fronto-striatal
      dysfunction in ADHD, but other functional networks of brain areas also appear to
      be implicated.

PMID- 19857517
TI  - Shared pain: from empathy to synaesthesia.
AB  - This paper reviews the current literature on "empathy for pain", the ability to
      understand pain observed in another person, in the context of a newly documented
      form of pain empathy "synaesthesia for pain". In synaesthesia for pain a person
      not only empathises with another's pain but experiences the observed or imagined
      pain as if it was their own. Neural mechanisms potentially involved in
      synaesthesia for pain include "mirror systems": neural systems active both when
      observing an action, or experiencing an emotion or sensation and when executing
      the same action, or personally experiencing the same emotion or sensation. For
      example, we may know that someone is in pain in part because observation
      activates similar neural networks as if we were experiencing that pain ourselves.
      We propose that synaesthesia for pain may be the result of painful and/or
      traumatic experiences causing disinhibition in the mirror system underlying
      empathy for pain. We will discuss this theory in the context of a documented
      group of amputees who experience synaesthesia for pain in phantom limbs.

PMID- 19857518
TI  - APP transgenic mice: the effect of active and passive immunotherapy in cognitive
      tasks.
AB  - Various immunotherapy strategies for APP transgenic mice have emerged in recent
      years. Specifically, active immunization with beta-amyloid (A beta) or passive
      immunization with anti-A beta-antibodies in APP transgenic mice has appeared most
      promising. Recent studies have shown that treatment of APP transgenic mice either
      with A beta(40/42) or A beta-specific antibodies can have beneficial effects in
      cognitive tasks. Active as well as passive immunization have been shown to affect
      spatial, non-spatial, emotional and object-related learning and memory. Such
      effects can be observed when treatments are applied prophylactically (before
      apparent A beta pathology) or therapeutically (after the development of A beta
      pathology) in APP transgenic mice. This review focuses on such cognitive outcomes
      of different active and passive immunization strategies in APP transgenic mice.

PMID- 19857519
TI  - How the immune system detects lipid antigens.
AB  - T lymphocytes are the cells of the immune system that may recognize glycolipids
      as antigens. T cells recognize lipids associated with the non-polymorphic
      molecules of the CD1 family present on the membrane of antigen-presenting cells.
      CD1 molecules contain hydrophobic pockets, which bind a large variety of lipid
      molecules in various manners. Lipid antigenicity is determined by their mode of
      uptake, membrane trafficking properties, degradation within endosomal
      compartments and capacity to form stable complexes with CD1. Extracellular and
      intracellular lipid binding proteins participate in lipid handling and loading on
      CD1 molecules within antigen-presenting cells. Recent crystal structures have
      disclosed how the T cell receptor contacts CD1-lipid complexes, revealing the
      contribution of both CD1 and lipid residues in making functionally relevant
      contacts. Lipid-specific T cells are important in autoimmunity, cancer
      surveillance, protection during infections, and in immunoregulation. The
      immunogenicity of lipids is being exploited in novel approaches to immunotherapy,
      including inhibition of autoimmunity and anti-cancer and bacterial vaccines.

PMID- 19857520
TI  - An alternative to fish oils: Metabolic engineering of oil-seed crops to produce
      omega-3 long chain polyunsaturated fatty acids.
AB  - It is now accepted that omega-3 polyunsaturated fatty acids, especially
      eicosapentaenoic acid (EPA; 20:5Delta5,8,11,14,17) and docosahexaenoic acid (DHA,
      22:6Delta4,7,10,13,16,19) play important roles in a number of aspects of human
      health, with marine fish rich in these beneficial fatty acids our primary dietary
      source. However, over-fishing and concerns about pollution of the marine
      environment indicate a need to develop alternative, sustainable sources of very
      long chain polyunsaturated fatty acids (VLC-PUFAs) such as EPA and DHA. A number
      of different strategies have been considered, with one of the most promising
      being transgenic plants "reverse-engineered" to produce these so-called fish
      oils. Considerable progress has been made towards this goal and in this review we
      will outline the recent achievements in demonstrating the production of omega-3
      VLC-PUFAs in transgenic plants. We will also consider how these enriched oils
      will allow the development of nutritionally-enhanced food products, suitable
      either for direct human ingestion or for use as an animal feedstuff. In
      particular, the requirements of aquaculture for omega-3 VLC-PUFAs will act as a
      strong driver for the development of such products. In addition, biotechnological
      research on the synthesis of VLC-PUFAs has provided new insights into the
      complexities of acyl-channelling and triacylglycerol biosynthesis in higher
      plants.

PMID- 19857521
TI  - Understanding and managing the adverse effects of antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) has changed the landscape of HIV
      disease in a way that seemed unthinkable a decade ago; from an almost uniformly
      fatal disease to a chronic manageable one. The first HAART regimens worked in
      suppressing virus, but were encumbered by a variety of short term and long term
      side effects. More recent regimens became simpler, easier to take, and with fewer
      adverse events. As we look to people living perhaps a normal life span with HIV,
      the increasing number of antiretroviral agents available means that
      individualizing treatment has become more feasible and the longer downstream
      adverse events related to HAART, such as its effect on cardiovascular disease and
      diabetes, renal and hepatic disease, have begun to dominate our choice of drugs.
      A knowledge of both the short and long term adverse events associated with HAART
      is essential for providers and for patients. For new drugs to be acceptable in
      the current field, they will have to pass a litmus test of tolerability. Since
      adverse events are often remarkably idiosyncratic, pharmacogenomics may offer a
      way of predicting side effects and their severity from a particular drug or drug
      class in individual patients. This article forms part of a special issue of
      Antiviral Research marking the 25th anniversary of antiretroviral drug discovery
      and development, Vol. 85, issue 1, 2010.

PMID- 19857522
TI  - Debio-025 inhibits HIV-1 by interfering with an early event in the replication
      cycle.
AB  - Cyclophilin A is a peptidyl-propyl isomerase that binds the capsid (p24) protein
      of HIV-1 and facilitates replication. We report a cyclophilin inhibitor, a non
      immunosuppressive cyclosporine analogue, Debio-025, that is about 15-times more
      potent than cyclosporine A and less toxic resulting in a selectivity index of
      more than 300. It was equally active against virus strains that were resistant
      toward inhibitors of the viral entry, fusion, or reverse transcription while it
      was not inhibitory to HIV-2 or SIV(MAC). Mechanism of action studies demonstrate
      that Debio-025 inhibits the HIV-1 replication by interfering with an early stage
      of the viral replication cycle. Indeed, addition of Debio-025 could be postponed
      for 2h before loosing its antiviral activity. The compound proved inactive
      against mutant viruses that are independent of cyclophilin A binding suggesting
      Debio-025 targets the cyclophilin A-capsid interaction.

PMID- 19857524
TI  - In vitro inhibition of the replication of classical swine fever virus by capsid
      targeted virus inactivation.
AB  - Classical swine fever virus (CSFV) is the causative agent of classical swine
      fever (CSF), a highly contagious fatal disease of swine. Few effective antiviral
      drugs are currently available against CSFV infections. To explore the feasibility
      of using capsid-targeted viral inactivation (CTVI) as an antiviral strategy
      against CSFV infections, we expressed the CSFV capsid protein (Cap) fused with
      the nuclease of Staphylococcus aureus (SN) in Escherichia coli and investigated
      its effects on the replication of CSFV in PK-15 cells. The results indicated that
      the fusion protein Cap-SN showed a strong Ca(2+)-dependent nuclease activity and
      inhibited the replication of CSFV in a dose-dependent manner, with complete
      inhibition at a concentration of 15 microg/ml, whereas the Cap fused with an
      enzymatically inactive SN (Cap-SN*) showed no nuclease activity or antiviral
      effects. Thus, the CTVI approach might be applicable to CSFV inhibition as a
      novel antiviral strategy.

PMID- 19857525
TI  - Inhibition of STAT1 methylation is involved in the resistance of hepatitis B
      virus to Interferon alpha.
AB  - As a major therapy for hepatitis B virus (HBV) infection, Interferon alpha (IFN
      alpha) triggers intracellular signal transduction including JAK-STAT pathway to
      produce various antiviral effector mechanisms. However, patients with chronic
      hepatitis B usually show low response to IFN-alpha treatment and the underlying
      mechanism remains unclear. In the present study, HepG2 and HepG2.2.15 cells were
      used to examine the Type I IFN receptors expression, phosphorylation and
      methylation of STAT1. STAT1-PIAS1 interaction in cells was tested by protein co
      immunoprecipitation. The potential improvement of S-adenosylmethionine (SAM) in
      the antiviral effect of IFN-alpha was also investigated. Our data demonstrated
      that both chains of the Type I IFN receptors were expressed for a much higher
      extent in HepG2.2.15 cells than in HepG2 cells. HBV inhibited dramatically the
      methylation rather than the phosphorylation of STAT1, which was consistent with
      an increased STAT1-PIAS1 interaction. Combined with IFN-alpha, SAM treatment
      effectively improved STAT1 methylation and attenuated STAT1-PIAS1 binding,
      followed by increased PKR and 2',5'-OAS mRNA expression, thus significantly
      reducing the HBsAg, HBeAg protein levels and HBV DNA load in the supernatant of
      HepG2.2.15 cells. Less STAT1 methylation and subsequent increased STAT1-PIAS1
      interaction are involved in the mechanism of the IFN-alpha-antagonistic activity
      of HBV. By improving STAT1 methylation, SAM can enhance the antiviral effect of
      IFN-alpha.

PMID- 19857523
TI  - Present and future arboviral threats.
AB  - Arthropod-borne viruses (arboviruses) are important causes of human disease
      nearly worldwide. All arboviruses circulate among wild animals, and many cause
      disease after spillover transmission to humans and agriculturally important
      domestic animals that are incidental or dead-end hosts. Viruses such as dengue
      (DENV) and chikungunya (CHIKV) that have lost the requirement for enzootic
      amplification now produce extensive epidemics in tropical urban centers. Many
      arboviruses recently have increased in importance as human and veterinary
      pathogens using a variety of mechanisms. Beginning in 1999, West Nile virus (WNV)
      underwent a dramatic geographic expansion into the Americas. High amplification
      associated with avian virulence coupled with adaptation for replication at higher
      temperatures in mosquito vectors, has caused the largest epidemic of arboviral
      encephalitis ever reported in the Americas. Japanese encephalitis virus (JEV),
      the most frequent arboviral cause of encephalitis worldwide, has spread
      throughout most of Asia and as far south as Australia from its putative origin in
      Indonesia and Malaysia. JEV has caused major epidemics as it invaded new areas,
      often enabled by rice culture and amplification in domesticated swine. Rift
      Valley fever virus (RVFV), another arbovirus that infects humans after
      amplification in domesticated animals, undergoes epizootic transmission during
      wet years following droughts. Warming of the Indian Ocean, linked to the El Nino
      Southern Oscillation in the Pacific, leads to heavy rainfall in east Africa
      inundating surface pools and vertically infected mosquito eggs laid during
      previous seasons. Like WNV, JEV and RVFV could become epizootic and epidemic in
      the Americas if introduced unintentionally via commerce or intentionally for
      nefarious purposes. Climate warming also could facilitate the expansion of the
      distributions of many arboviruses, as documented for bluetongue viruses (BTV),
      major pathogens of ruminants. BTV, especially BTV-8, invaded Europe after climate
      warming and enabled the major midge vector to expand is distribution northward
      into southern Europe, extending the transmission season and vectorial capacity of
      local midge species. Perhaps the greatest health risk of arboviral emergence
      comes from extensive tropical urbanization and the colonization of this expanding
      habitat by the highly anthropophilic (attracted to humans) mosquito, Aedes
      aegypti. These factors led to the emergence of permanent endemic cycles of urban
      DENV and CHIKV, as well as seasonal interhuman transmission of yellow fever
      virus. The recent invasion into the Americas, Europe and Africa by Aedes
      albopictus, an important CHIKV and secondary DENV vector, could enhance urban
      transmission of these viruses in tropical as well as temperate regions. The
      minimal requirements for sustained endemic arbovirus transmission, adequate human
      viremia and vector competence of Ae. aegypti and/or Ae. albopictus, may be met by
      two other viruses with the potential to become major human pathogens: Venezuelan
      equine encephalitis virus, already an important cause of neurological disease in
      humans and equids throughout the Americas, and Mayaro virus, a close relative of
      CHIKV that produces a comparably debilitating arthralgic disease in South
      America. Further research is needed to understand the potential of these and
      other arboviruses to emerge in the future, invade new geographic areas, and
      become important public and veterinary health problems.

PMID- 19857526
TI  - Silibinin attenuates cognitive deficits and decreases of dopamine and serotonin
      induced by repeated methamphetamine treatment.
AB  - Cognitive deficits are a core feature of patients with methamphetamine (METH)
      abuse. It has been reported that repeated METH treatment impairs long-term
      recognition memory in the novel object recognition test (NORT) in mice. Recent
      studies indicate that silibinin, a flavonoid derived from the herb milk thistle,
      has potent neuroprotective effects in cell cultures and several animal models of
      neurological diseases. However, its effect on the cognitive deficit induced by
      METH remains unclear. In the present study, we attempt to clarify the effect of
      silibinin on impairments of recognition memory caused by METH in mice. Mice were
      co-administered silibinin with METH for 7 days and then cognitive function was
      assessed by NORT after 7-day withdrawal. Tissue levels of dopamine and serotonin
      as well as their metabolites in the prefrontal cortex and hippocampus were
      measured 1 day after NORT. Silibinin dose-dependently ameliorated the impairment
      of recognition memory caused by METH treatment in mice. Silibinin significantly
      attenuated the decreases in the dopamine content of the prefrontal cortex and
      serotonin content of the hippocampus caused by METH treatment. We also found a
      correlation between the recognition values and dopamine and serotonin contents of
      the prefrontal cortex and hippocampus. The effect of silibinin on cognitive
      impairment may be associated with an amelioration of decreases in dopamine and
      serotonin levels in the prefrontal cortex and hippocampus, respectively. These
      results suggest that silibinin may be useful as a pharmacological tool to
      investigate the mechanisms of METH-induced cognitive impairments.

PMID- 19857527
TI  - Scent marking by the male domestic rabbit (Oryctolagus cuniculus) is stimulated
      by an object's novelty and its specific visual or tactile characteristics.
AB  - "Chinning" is a stereotyped scent marking behavior of domestic rabbits, in which
      the animal rubs the underside of its chin against objects in order to deposit
      scent gland secretions. Although the long-term maintenance of chinning requires
      circulating gonadal steroids, little is known about the acute regulation of this
      behavior. To define specific environmental stimuli that engage the chinning motor
      pattern, male rabbits were placed into an open field arena containing markable
      objects ("standard" bricks, "tall" bricks, or polished onyx spheres), observed
      for 30 min, returned to the home cage for 5 min, and then placed in the open
      field arena for another 30 min. During the 5 min interim: (1) the location of the
      open field or the spatial orientation of the objects within it were changed, (2)
      the olfactory or (3) visual characteristics of the objects were changed; or (4)
      no changes were made. Chinning and ambulation habituated to each type of object
      across the first 30 min, and bricks elicited more chinning than polished onyx
      spheres. In the second 30 min test, chinning was re-stimulated only when the
      original objects were replaced by visually different ones that had preferred
      characteristics. Ambulatory behavior was increased by changing the location of
      the open field arena, while modifying the olfactory characteristics of the
      objects had no effect on chinning or ambulation. These results indicate that
      scent marking is stimulated by object novelty and by the visual and/or tactile
      characteristics of the objects being marked.

PMID- 19857528
TI  - The mycolyltransferase 85A, a putative drug target of Mycobacterium tuberculosis:
      development of a novel assay and quantification of glycolipid-status of the
      mycobacterial cell wall.
AB  - The enzymes of the antigen 85 complex (Ag85A, B, and C) possess
      mycolyltransferase activity and catalyze the synthesis of the most abundant
      glycolipid of the mycobacterial cell wall, the cord factor. The cord factor
      (trehalose 6,6'-dimycolate, TDM) is essential for the integrity of the
      mycobacterial cell wall and pathogenesis of the bacillus. Thus, TDM biosynthesis
      is regarded as a potential drug target for control of Mycobacterium tuberculosis
      infections. Trehalose 6,6'-dimycolate (TDM) is synthesized from two molecules of
      trehalose-6'-monomycolate (TMM) by antigen 85A. We report here a novel enzyme
      assay using the natural substrate TMM. The novel colorimetric assay is based on
      the quantification of glucose from the degradation of trehalose, which is the
      product from catalytic activity of antigen 85A. Using the new assay, K(m) and
      K(cat) were determined with values of 129.6+/-8.1 microM and 65.4+/-4.1 min(-1),
      respectively. This novel assay is also suitable for robust high-throughput
      screening (HTS) for compound library screening against mycolyltransferase
      (antigen 85A). The assay is significantly faster and more convenient to use than
      all assays currently in use. The assay has a very low coefficient of variance
      (0.04) in 96-well plates and shows a Z' factor of 0.67-0.73, indicating the
      robustness of the assay. In addition, this new assay is highly suitable for the
      quantification of total TMM of the mycobacterial cell envelope.

PMID- 19857529
TI  - An improved and cost-effective cDNA-AFLP method to investigate transcription
      derived products when high throughput sequencing is not available.
AB  - Although the cost of high throughput sequencing is decreasing, the cost is still
      often too high for individual projects targeted at, e.g., genome-wide
      transcription profiling in non-model organisms. Then, a low-cost alternative is
      cDNA-AFLP, which we have now considerably modified in order to develop a faster
      and simpler method to identify and analyze genes involved in specific, possibly
      adaptive characteristics. Particularly, we wanted to exclude repetitive PCR
      amplifications, extensive cloning and the presence of overlapping transcripts,
      which all lower the efficiency of the method.

PMID- 19857530
TI  - Preparation of ubiquitin-conjugated proteins using an insect cell-free protein
      synthesis system.
AB  - Ubiquitination is one of the most significant posttranslational modifications
      (PTMs). To evaluate the ability of an insect cell-free protein synthesis system
      to carry out ubiquitin (Ub) conjugation to in vitro translated proteins, poly-Ub
      chain formation was studied in an insect cell-free protein synthesis system. Poly
      Ub was generated in the presence of Ub aldehyde (UA), a de-ubiquitinating enzyme
      inhibitor. In vitro ubiquitination of the p53 tumor suppressor protein was also
      analyzed, and p53 was poly-ubiquitinated when Ub, UA, and Mdm2, an E3 Ub ligase
      (E3) for p53, were added to the in vitro reaction mixture. These results suggest
      that the insect cell-free protein synthesis system contains enzymatic activities
      capable of carrying out ubiquitination. CBB-detectable ubiquitinated p53 was
      easily purified from the insect cell-free protein synthesis system, allowing
      analysis of the Ub-conjugated proteins by mass spectrometry (MS). Lys 305 of p53
      was identified as one of the Ub acceptor sites using this strategy. Thus, we
      conclude that the insect cell-free protein synthesis system is a powerful tool
      for studying various PTMs of eukaryotic proteins including ubiqutination
      presented here.

PMID- 19857531
TI  - Cloning, microbial expression and structure-activity relationship of polyphenol
      oxidases from Camellia sinensis.
AB  - Polyphenol oxidase (PPO) can be used for organic synthesis and degradation of
      wastes and dyes in industries. Lack of enzyme sources is a major barrier for its
      application. A PPO gene, with a full length of 1.8kb without introns, was cloned
      by PCR from genomic DNA of five common cultivars of Camellia sinensis. They had a
      98.2-99.9% degree of identity in nucleotides and 94.7-96.1% in amino acids and
      encoded a polypeptide of 599 amino acids with a signal peptide targeting the
      chloroplast and three Cu-binding domains. The mature PPO showed high expression
      and enzyme activity after refolding the inclusion bodies in Escherichia coli BL21
      (DE3) using pET30c expression vector, but low expression in Pichia pastoris GS115
      using both the secretory and non-secretory vectors pPICZalphaA and pPICZA. The
      expression of PPO mutants demonstrated that the signal sequences prevented
      recombinant gene expression in E. coli. PPO activity was not affected by the C
      terminus and was slightly inhibited by the CuC domain. Other domains were
      important for its activity. A 3.1-fold increase in PPO activity over non
      recombinant controls was obtained by expressing the PPO fragment without signal
      sequences and the CuC domain in E. coli BL21 (DE3) using the pET30c vector.

PMID- 19857532
TI  - The influence of polymer topology on pharmacokinetics.

PMID- 19857533
TI  - Development of a pH-responsive drug delivery system for enantioselective
      controlled delivery of racemic drugs.
AB  - This study aimed to develop enantioselective-controlled drug delivery systems for
      selective release of the required (S)-enantiomer in a dose formulation containing
      a racemic drug in response to pH stimuli. The recognition system was obtained
      from a nanoparticle-on-microsphere (NOM) molecularly imprinted polymer (MIP) with
      a multifunctional chiral cinchona anchor synthesised by suspension polymerisation
      using ethylene glycol dimethacrylate as a cross-linker. (S)-omeprazole was used
      as an imprinting molecule conferring stereoselectivity upon the polymers. The
      ability of the prepared recognition polymers to selectively rebind (S)-omeprazole
      was evident at different pH levels (the highest being at pH 7.4). The partial
      selective-release phenomenon of the (S)-enantiomer in MIP-containing composite
      cellulose membranes with increased vehicular racemic omeprazole concentrations
      was highly pH-dependent. Cinchona-bonded polymers imprinted with (S)-omeprazole
      could recognise the moldable contact site of (S)-omeprazole independently of its
      chirality; this is responsible for the delivery of (S)-enantiomer from racemic
      omeprazole. The controlled-release drug devices were fabricated with synthesised
      composite latex, and consisted of a pH stimuli-responsive poly(hydroxyethyl
      methacrylate) (HEMA) and polycaprolactone-triol (PCL-T) blend, and a MIP with
      preloaded drug, along with pH 7.4 buffer in the device's interior. The results
      demonstrate that drug delivery systems containing (S)-omeprazole imprinted
      cinchona-polymer nanoparticle-on-microspheres may maximise efficacy while
      minimising dose frequency.

PMID- 19857534
TI  - PEGylation of bacterial cocaine esterase for protection against protease
      digestion and immunogenicity.
AB  - Enhancing cocaine metabolism by administration of cocaine esterase (CocE) has
      been considered as a promising treatment strategy for cocaine overdose and
      addiction, as CocE is the most efficient native enzyme yet identified for
      metabolizing the naturally occurring cocaine. A major obstacle to the clinical
      application of CocE, however, lies in its thermo-instability, rapid degradation
      by circulating proteases, and potential immunogenicity. PEGylation, namely by
      modifying a protein or peptide compound via attachment of polyethylene glycol
      (PEG) chains, has been proven to overcome such problems and was therefore
      exploited in this CocE investigation. The PEG-CocE conjugates prepared in this
      study showed a purity of greater than 93.5%. Attachment of PEG to CocE apparently
      inhibited the binding of anti-CocE antibodies to the conjugate, as demonstrated
      by the enzyme-linked immunosorbent assay (ELISA) assay. In addition, PEGylation
      yielded protection to CocE against thermal degradation and protease digestion.
      Furthermore, preliminary in vivo results suggested that, similarly to native
      CocE, the PEG-CocE conjugates were able to protect animals from cocaine-induced
      toxic effects. Overall, this study provides evidence that the PEGylation may
      serve as a tool to prolong CocE functionality in the circulation and reduce its
      potential immunogenicity.

PMID- 19857535
TI  - Improving the provision of meals in hospital. The patients' viewpoint.
AB  - This study examines the provision of hospital meals from the patients' viewpoint,
      with the aim of improving hospital food service. Patients were approached in
      early 2008 in a National Health Service hospital in the South of England and
      invited to comment on the good and bad aspects of eating in hospital. Comments
      were collected in an abbreviated "key word" format which incurred the minimum of
      bias and allowed emergent themes to be analysed both quantitatively and
      qualitatively. Seven main themes emerged, of which "food" and "choice" were
      mentioned most frequently, but had a low ratio (1.8 and 1.7, respectively) of
      approving over disapproving comments. The next most mentioned theme, "service
      staff", showed the highest approving/disapproving ratio (4.8) overall. Less
      frequent themes were: "meals and lifestyle", "timing and routine", "service
      quality" and "food quantity". These data, together with qualitative analysis of
      the responses showed patients' views of hospital food to be positive, on the
      whole meeting or surpassing their expectations. However, these expectations were
      low, the experience of eating in hospital contrasted unfavourably with home, and
      the meals were at best a distraction from the rigours of hospital treatment.
      Service staff were positively regarded because they offered an important
      opportunity for "normal" discourse with a non-medical person. On the basis of the
      findings, changes are recommended in the management of service staff, menus, food
      presentation, nutritional intake and patients' lifestyle. Of these, the first is
      likely to have most impact on the experience and viewpoint of hospital patients.

PMID- 19857536
TI  - A novel member of the adipokinetic peptide family in a "living fossil", the ice
      crawler Galloisiana yuasai, is the first identified neuropeptide from the order
      Grylloblattodea.
AB  - This is the first report on the structural identity of a neuropeptide of the
      insect order Grylloblattodea. A peptide was isolated and sequenced from the
      retrocerebral corpora cardiaca-corpora allata complex of the ice crawler,
      Galloisiana yuasai. The sequence of the peptide was deduced from the multiple
      MS(N) electrospray mass data as that of an octapeptide: pGlu-Val-Asn-Phe-Ser-Pro
      Thr-Trp amide. The retention time on reversed-phase HPLC and the CID MS(2) mass
      spectra of a synthetic peptide with the same primary structure were exactly the
      same as of the natural peptide. The sequence represents a novel peptide of the
      adipokinetic hormone family which contains presently 50 members. The primary
      structure differs in only one position to a few previously discovered AKHs. A
      scenario is outlined that makes it likely that the most recently discovered
      insect order, the Mantophasmatodea, and the Grylloblattodea are closely related.

PMID- 19857537
TI  - Broken heart or takotsubo syndrome: support for the neurohumoral hypothesis of
      stress cardiomyopathy.

PMID- 19857538
TI  - The hOGG1 Ser326Cys polymorphism and Huntington's disease.
AB  - Increasing evidence supports a role for oxidative DNA damage and impaired DNA
      repair mechanisms in the pathogenesis of age related neurodegenerative diseases.
      Within this context there is a current interest in the understanding of the role
      played by polymorphisms of DNA repair genes in the inter-individual risk to
      develop neurodegenerative pathologies, as well as in the onset and the
      progression of disease symptoms. Particularly, somatic CAG repeat expansion of
      the gene encoding for huntingtin has been observed in tissues of patients
      affected by Huntington's disease (HD), including blood and brain. Recent evidence
      suggests that somatic CAG repeat expansion in HD cells might contribute to
      disease age at onset and is mediated by the DNA repair OGG1 enzyme, during the
      removal of 8-oxoguanine (8-oxoG) from the DNA. There is also evidence that the
      expression of hMTH1, which removes 8-oxoG from the nucleotide pool, protects mice
      from HD-like symptoms, and progenitor striatal cells from the toxic effects of
      the mutant huntingtin. The hOGG1 Ser326Cys polymorphism results in reduced OGG1
      activity and increased 8-oxoG formation. In the present study, performed on blood
      DNA from 91 HD subjects, we observed that bearers of the mutant Cys326 allele
      (Ser326Cys+Cys326Cys) tend to have an increased number of CAG repeats of the
      expanded HD allele (P=0.049); moreover bearers of at least one copy of the mutant
      Cys326 allele, mainly heterozygous subjects, showed a significant (P=0.041)
      earlier disease onset than Ser326Ser wild-type individuals, suggesting a possible
      role of the hOGG1 Ser326Cys polymorphism in HD phenotype.

PMID- 19857539
TI  - Toward a molecular classification of cancer.
AB  - The diagnosis of cancer is typically made on the basis of clinical and
      histological criteria. However, molecular biology research over the past three
      decades has revealed that diagnoses based on clinical presentation and pathology
      evaluation are not always accurate. With the advent of molecularly targeted
      drugs, a reclassification of cancers, based on their underlying genetic defects,
      is becoming increasingly urgent.

PMID- 19857540
TI  - The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis.
AB  - Although several specific micronutrient deficiencies are associated with disease
      progression and increased mortality risk in HIV/AIDS, and even a simple
      multivitamin/mineral supplement can prolong survival, this is typically viewed
      merely as nutritional support of the immune system, and only necessary if there
      are deficiencies to be rectified. However, the reality is more complex. Several
      striking nutrient-related metabolic abnormalities have been consistently
      documented in HIV infection. One is chronic oxidative stress, including a drastic
      depletion of cysteine from the glutathione pool, and a progressive decline of
      serum selenium that is correlated with disease progression and mortality. Another
      is decreased blood levels of tryptophan, with an associated intracellular niacin
      deficiency. Tryptophan depletion or "deletion" by induction of indoleamine-2,3
      dioxygenase (IDO), the first step in oxidative tryptophan metabolism, is a known
      mechanism for immune suppression that is of critical importance in cancer and
      pregnancy, and, potentially, in HIV/AIDS. Existing evidence supports the
      hypothesis that these nutrient-related metabolic abnormalities in HIV infection
      regarding antioxidants, selenium, sulfur, tryptophan and niacin are interrelated,
      because HIV-associated oxidative stress can induce niacin/NAD+ depletion via
      activation of poly(ADP-ribose) polymerase (PARP), which could lead to tryptophan
      oxidation for compensatory de novo niacin synthesis, thereby contributing to
      immune tolerance and T-cell loss via tryptophan deletion and PARP-induced cell
      death. This "oxidative stress-induced niacin sink" (OSINS) model provides a
      mechanism whereby the oxidative stress associated with HIV infection can
      contribute to immunosuppression via tryptophan deletion. This model is directly
      supported by evidence that antioxidants can counteract indoleamine-2,3
      dioxygenase (IDO), providing the critical link between oxidative stress and
      tryptophan metabolism proposed here. The OSINS model can be used to guide the
      design of nutraceutical regimens that can effectively complement antiretroviral
      therapy for HIV/AIDS.

PMID- 19857541
TI  - Mouse pulmonary dose- and time course-responses induced by exposure to multi
      walled carbon nanotubes.
AB  - Carbon nanotubes (CNT) come in a variety of types, but one of the most common
      forms is multi-walled carbon nanotubes (MWCNT). MWCNT have potential applications
      in many diverse commercial processes, and thus human exposures are considered to
      be likely. In order to investigate the pulmonary toxicity of MWCNT, we conducted
      an in vivo dose-response and time course study of MWCNT in mice in order to
      assess their ability to induce pulmonary inflammation, damage, and fibrosis using
      doses that approximate estimated human occupational exposures. MWCNT were
      dispersed in dispersion medium (DM) and male C57BL/6J mice (7 weeks old) received
      either DM (vehicle control), 10, 20, 40 or 80mug MWCNT by aspiration exposure. At
      1, 7, 28 and 56 days post-exposure, MWCNT-induced pulmonary toxicity was
      investigated. Bronchoalveolar lavage (BAL) studies determined pulmonary
      inflammation and damage was dose-dependent and peaked at 7 days post-exposure. By
      56 days post-exposure, pulmonary inflammation and damage markers were returning
      to control levels, except for the 40mug MWCNT dose, which was still significantly
      higher than vehicle control. Histopathological studies determined that MWCNT
      exposure caused rapid development of pulmonary fibrosis by 7 days post-exposure,
      that granulomatous inflammation persisted throughout the 56-day post-exposure
      period, and also demonstrated that MWCNT can reach the pleura after pulmonary
      exposure. In summary, the data reported here indicate that MWCNT exposure rapidly
      produces significant adverse health outcomes in the lung. Furthermore, the
      observation that MWCNT reach the pleura after aspiration exposure indicates that
      more extensive investigations are needed to fully assess if pleural penetration
      results in any adverse health outcomes.

PMID- 19857542
TI  - Effect of an antioxidant functional food beverage on exercise-induced oxidative
      stress: a long-term and large-scale clinical intervention study.
AB  - The efficacy of long-term intake of a novel functional food supplement FuncionaTM
      containing vitamins and juiced fruits was evaluated in order to assess the net
      effect of physical activity and antioxidant potentials in healthy older adult
      population. The long-term (2 years) and large-scale (400 older adult subjects)
      interventional study was based on both moderate-intensity exercise practice and
      concurrent supplementation. Sustained exercise-induced oxidative stress as
      reflected in significantly increased blood thiobarbituric acid-reactive
      substances (TBARS) (+15%), protein carbonyl groups (PC) (+18%) and oxidized
      glutathione (GSSG) (+112%) concentrations, and leukocyte 8-OHdG contents (23%).
      Exercise decreased the reduced/oxidized glutathione (GSH/GSSG) molar ratio (-43%)
      and plasma vitamin C levels (-22%). Supplementation with FuncionaTM was
      significant in preventing oxidative damage to lipid, protein and DNA, and
      normalizing blood GSSG, GSH/GSSG and vitamin C levels. Thus daily intake of the
      antioxidant functional beverage counteracts the exercise-induced oxidative stress
      in free-living older subjects, and might be necessary to restore impaired
      antioxidant balance due long-term regular exercise.

PMID- 19857543
TI  - Epidemiology-driven neurodevelopmental animal models of schizophrenia.
AB  - Human epidemiological studies have provided compelling evidence that the risk of
      developing schizophrenia is significantly enhanced following prenatal and/or
      perinatal exposure to various environmental insults, including maternal exposure
      to stress, infection and/or immune activation, nutritional deficiencies and
      obstetric complications. Based on these associations, a great deal of interest
      has been centered upon the establishment of neurodevelopmental animal models
      which are based on prenatal and/or perinatal exposure to such environmental
      stimuli. In the present review, we describe this relatively novel class of
      epidemiology-based animal models in relation to the etiology, neurobiology and
      psychopharmacology of schizophrenia. Thereby, we discuss the general design and
      practical implementation of these models, and we provide an integrative summary
      of experimental findings derived from diverse epidemiology-based models,
      including models of maternal exposure to psychological stress, glucocorticoid
      treatment, viral infection, immune activating agents, protein deprivation,
      vitamin D deficiency, as well as models of obstetric complications in the form of
      birth by Caesarian section and perinatal/postnatal hypoxia. We highlight that the
      long-term consequences of prenatal exposure to these environmental challenges in
      animals successfully capture a broad spectrum of structural and functional brain
      abnormalities implicated in schizophrenia, some of which can be normalized by
      acute and/or chronic antipsychotic drug treatment. We thus conclude that
      epidemiology-driven neurodevelopmental models of schizophrenia are characterized
      by a high level of face, construct and predictive validity, including intrinsic
      etiological significance to the disorder. They also fulfill the expectation of
      the neurodevelopmental theory, such that the effects of prenatal environmental
      insults often only emerge after puberty. Epidemiologically based animal models
      not only provide indispensable experimental tools to test the hypothesis of
      causality in human epidemiological associations, but they also offer important
      new avenues for the elucidation of neurobiological, neuroendocrine and
      neuroimmunological mechanisms involved in the etiopathogenesis of schizophrenia
      and related disorders.

PMID- 19857545
TI  - HIV and antiretroviral therapy: impact on the central nervous system.
AB  - The HIV pandemic represents a major source of neurological morbidity worldwide.
      Emerging data from diverse populations indicate that HIV leads to significant
      neurocognitive impairments that reduce individuals' ability to contribute to the
      well being of their families and society. HIV affects vulnerable populations with
      many comorbidities, but the virus contributes to neurocognitive impairment
      independent of these conditions. The neuropathological substrate of HIV
      neurocognitive disorders is damage to synapses and dendrites, without major
      neuronal loss. This suggests the potential for substantial reversibility if
      synaptodendritic function can be restored. In the developed world, combination
      antiretroviral therapy (CART) leads to improved neurocognitive function as well
      as morbidity and mortality in HIV. CART is being used in increasing numbers of
      individuals in resource limited settings. New cases of severe dementia are now
      rare in populations where effective CART has been deployed. While some degree of
      neurocognitive improvement with CART is almost universal, many individuals do not
      achieve full restoration of their premorbid neurocognitive status, and milder
      degrees of impairment remain quite prevalent. Optimizing neurocognitive recovery
      is likely to require the development of better CNS penetrating antiretroviral
      regimens and the use of neuroprotective agents.

PMID- 19857546
TI  - Melatonin maintains adult hippocampal neurogenesis and cognitive functions after
      irradiation.
AB  - Cognitive health of an organism is considered to be maintained by the capacity of
      hippocampal precursors to proliferate and differentiate. Environmental stressors
      including irradiation have been shown to inhibit neurogenesis and are associated
      with the onset of cognitive impairments. Over the last two decades, much evidence
      has been gathered showing that enhanced free radical levels and an impaired
      antioxidant pool are important factors underlying the pathophysiological
      mechanisms in a variety of neurocognitive and neurodegenerative ailments. Since
      oxidative stress is reported to be implicated in impaired neurogenesis, it is
      likely that antioxidants such as melatonin and its metabolites could restore or
      minimize cellular death in the hippocampal dentate gyrus. The present review
      summarizes the recent studies documenting the protective role of melatonin
      against radiation-induced impairment of neurogenesis and cognitive functions.

PMID- 19857547
TI  - Coexpression of CD44 variant isoforms and receptor for hyaluronic acid-mediated
      motility (RHAMM, CD168) is an International Prognostic Index and C-MYC gene
      status-independent predictor of poor outcome in diffuse large B-cell lymphomas.
AB  - OBJECTIVE: Expression of CD44 variant (v) isoforms substantiates poor prognosis
      in patients with hematological malignancies. We have previously shown that CD44v6
      expression in diffuse large B-cell lymphoma (DLBCL) correlates with advanced
      disease stage and is predominantly detected in non-germinal center B-cell-like
      DLBCL subtypes. With the growing number of associated molecules found to form
      functional complexes with CD44, we analyzed a larger cohort of cyclophosphamide,
      doxorubicin, vincristine, prednisone, and equivalently treated DLBCL patients to
      define the prognostic role of such CD44-associated molecules. MATERIALS AND
      METHODS: Two-hundred and ninety formalin-fixed, paraffin-embedded primary DLBCL
      tissue samples were analyzed in tissue microarrays. To obtain potential
      biologically meaningful associations, optimal cutoff values were established by
      receiver operating characteristic curves. The prognostic significance of every
      possible multimarker phenotype was also addressed. RESULTS: We showed that
      coexpression of any of the CD44v with the receptor for hyaluronic acid-mediated
      motility (RHAMM, CD168) identifies a subgroup of DLBCL patients with a very poor
      prognosis, independent of the International Prognostic Index. These patients did
      not show C-MYC translocations or amplifications. CD44v-RHAMM coexpression was
      most prevalent in non-germinal center DLBCL cases and usually coincided with
      expression of osteopontin. CONCLUSION: Evaluation of CD44v-RHAMM coexpression may
      improve the accuracy of DLBCL prognosis and identify a subgroup of patients who
      will benefit from therapeutic alternatives to cyclophosphamide, doxorubicin,
      vincristine, and prednisone.

PMID- 19857548
TI  - Role of neurotensin receptor 1 in the regulation of food intake by neuromedins
      and neuromedin-related peptides.
AB  - Central administration of neuromedins and neuromedin-related peptides suppresses
      food intake in rodents. Neurotensin- and neuromedin U (NMU)-induced anorexia is
      mainly mediated through neurotensin receptor 1 (Ntsr1) and NMU receptor 2,
      respectively. Xenin belongs to the neurotensin family and suppresses food intake
      via an unknown receptor. It has been suggested that Ntsr1 also mediates
      biological actions of xenin and NMU. Therefore, we examined the effect of
      intracerebroventricular injection of xenin and NMU on food intake and body weight
      in wild-type and Ntsr1-deficient mice. The feeding-suppressing and weight gain
      inhibiting effects of xenin were abolished in Ntsr1-deficient mice, but NMU
      reduced food intake and body weight gain in both wild-type and Ntsr1-deficient
      mice. These findings support the role for Ntsr1 in the mediation of the metabolic
      effect of xenin as well as neurotensin. Therefore, enhancement of signaling
      through the Ntsr1 receptor is a potential strategy to reduce appetite and
      ameliorate obesity.

PMID- 19857544
TI  - The TIP39-PTH2 receptor system: unique peptidergic cell groups in the brainstem
      and their interactions with central regulatory mechanisms.
AB  - Tuberoinfundibular peptide of 39 residues (TIP39) is the recently purified
      endogenous ligand of the previously orphan G-protein coupled parathyroid hormone
      2 receptor (PTH2R). The TIP39-PTH2R system is a unique neuropeptide-receptor
      system whose localization and functions in the central nervous system are
      different from any other neuropeptides. TIP39 is expressed in two brain regions,
      the subparafascicular area in the posterior thalamus, and the medial
      paralemniscal nucleus in the lateral pons. Subparafascicular TIP39 neurons seem
      to divide into a medial and a lateral cell population in the periventricular gray
      of the thalamus, and in the posterior intralaminar complex of the thalamus,
      respectively. Periventricular thalamic TIP39 neurons project mostly to limbic
      brain regions, the posterior intralaminar thalamic TIP39 neurons to
      neuroendocrine brain areas, and the medial paralemniscal TIP39 neurons to
      auditory and other brainstem regions, and the spinal cord. The widely distributed
      axon terminals of TIP39 neurons have a similar distribution as the PTH2R
      containing neurons, and their fibers, providing the anatomical basis of a
      neuromodulatory action of TIP39. Initial functional studies implicated the TIP39
      PTH2R system in nociceptive information processing in the spinal cord, in the
      regulation of different hypophysiotropic neurons in the hypothalamus, and in the
      modulation of affective behaviors. Recently developed novel experimental tools
      including mice with targeted mutations of the TIP39-PTH2R system and specific
      antagonists of the PTH2R will further facilitate the identification of the
      specific roles of TIP39 and the PTH2R.

PMID- 19857549
TI  - Morphology and cell classification of large neurons in the adult human dentate
      nucleus: a quantitative study.
AB  - The dentate nucleus represents the most lateral of the four cerebellar nuclei
      that serve as a major relay centres for fibres coming from the cerebellar cortex.
      Although many relevant findings regarding to the three-dimensional structure, the
      neuronal morphology and the cytoarchitectural development of the dentate nucleus
      have been presented so far, very little quantitative information has been
      collected to further explain several types of large neurons in the dentate
      nucleus. In this study we quantified the morphology of the large dentate neurons
      in the adult human taking, into account seven morphometric parameters that
      describe the main properties of the cell soma, the dendritic field and the
      dendritic branching pattern. Since the lateral cerebellar nucleus in the cat and
      other lower mammals is homologous to the dentate nucleus in primates and man, we
      have classified our sample of large neurons in accordance with the shape of the
      cell body, the dendritic arborization and their location within the dentate
      nucleus. By performing the appropriate statistical analysis, we have proved that
      our sample of human dentate neurons can be classified into four distinct types.
      In that sense, our quantitative analysis verifies the validity of previous
      qualitative conclusions concerning the large neurons in the developing human
      dentate nucleus. Furthermore, the present study represents the first attempt to
      perform a quantitative analysis and cell classification of the large projection
      neurons in the adult human dentate nucleus.

PMID- 19857551
TI  - Serum levels of interleukin-6 are elevated in patients with Parkinson's disease
      and correlate with physical performance.
AB  - Some studies have demonstrated altered circulating levels of cytokines, including
      IL-6, in Parkinson's disease (PD), implying a possible involvement of
      inflammatory and immune-mediated mechanisms in its pathogenesis. Moreover, the
      increased production of inflammatory cytokines has been associated with cognitive
      impairment and poor physical performance in the elderly. We compared serum levels
      of IL-6 in 44 PD patients and 22 healthy subjects, and correlated them with PD
      specific instruments and functional tests. Serum levels of IL-6 were
      significantly increased in PD (p=0.015). There was no correlation between serum
      levels of IL-6 and instruments traditionally used to assess PD severity. However,
      we found that PD patients with higher serum levels of IL-6 spent more time at
      functional mobility tests and had lower gait speed. Also, these patients had
      major problems to keep balance during functional tasks that required postural
      changes and that had a reduced base support. These results showed that high
      levels of IL-6 can be involved with an acceleration of muscle catabolism leading
      to sarcopenia, therefore contributing to weakness and fatigue, and may also be
      associated with functional disability in PD.

PMID- 19857550
TI  - Increased prevalence of val(66)met BDNF genotype among subjects with cervical
      dystonia.
AB  - Abnormalities of cortical representational maps and their plasticity have been
      described in dystonia. A common polymorphism for BDNF has been associated with
      abnormal cortical plasticity, and thus might contribute to pathogenesis of
      dystonia in some subjects. As a first step towards this suggestion, the current
      study examined the prevalence of this polymorphism. BDNF genotype was examined in
      34 subjects with cervical dystonia, 54 age-matched healthy controls, and 53
      subjects with a different movement disorder, Parkinson's disease. ApoE genotype,
      known to influence neurological outcome in some conditions, was also examined as
      a control. In subjects with cervical dystonia, the val(66)met polymorphism was
      approximately twice as prevalent when compared to either control group. This was
      not true of ApoE genotype, which was similarly distributed across subject groups.
      The current findings suggest that the BDNF val(66)met polymorphism might play a
      role in the pathogenesis of cervical dystonia in some subjects.

PMID- 19857552
TI  - Developmental and aging change of orexin-A and -B immunoreactive neurons in the
      male rat hypothalamus.
AB  - Orexin/hypocretin is indicated to affect various physiological functions and
      behaviors, such as energy balance, feeding, wake-sleep cycle, stress response,
      and reproduction. This study investigated postnatal development and aging changes
      of the orexin neuron in the male rat hypothalamus. The brain tissue of rats from
      1 week to 24 months old was analyzed by immunohistochemistry for two forms of
      orexin peptides, orexin-A and -B. The number of immunoreactive cells for each age
      group was counted and the immunoreactive intensity was also analyzed in order to
      reveal the changes in the number of expressing cells and the relative amount of
      the peptides. The number of orexin immunoreactive cells increased from postnatal
      2 weeks to maturation, then slightly decreased and stabilized until the age of 8
      months old, but it was significantly decreased by 24 months old. The intensity of
      the immunoreaction followed almost the same pattern. Our findings demonstrate
      that orexin neurons are increased during maturation and then are significantly
      decreased during the period from 8 to 24 months old, indicating an involvement of
      orexin in the physiological changes in rat aging such as energy balance, sleep,
      stress response, and reproduction.

PMID- 19857553
TI  - Influence of aging on the calbindin-D-28k immunoreactive positive dopaminergic
      neurons in the substantia nigra pars compacta of rats.
AB  - We studied the relationship between aging and the vulnerability of substantia
      nigra pars compacta (SNc) calbindin-D-28k immunoreactive positive (CB+)
      dopaminergic (DA) neurons. Immunohistochemistry and cell counting were used to
      determine the number of CB+ DA neuron in aged rats (24 mon) compared to adult
      rats (5 mon). Furthermore, the expression of CB mRNA and protein levels in SN was
      studied by semi-quantitative RT-PCR and Western blotting. An 11% loss of CB+ DA
      neurons was detected in both the rostral (8.9%) and caudal (1.7%) segments but
      not in the intermedial segment of SNc in aged rats compared to adult rats
      (P<0.05). No difference was detected in CB mRNA and protein levels between aged
      and adult rats (P>0.05). These data suggest that expression levels of CB mRNA and
      protein may increase in the existing SNc DA neurons, which may compensate for the
      partial age dependent loss of CB+ DA neurons in the SNc.

PMID- 19857554
TI  - Estradiol-17beta-responsive A1 and A2 noradrenergic cells of the brain stem
      project to the bed nucleus of the stria terminalis in the ewe brain: a possible
      route for regulation of gonadotropin releasing hormone cells.
AB  - We have studied brain stem cells in the ewe brain that project to the bed nucleus
      of the stria terminalis (BNST) and determined if these cells are activated by
      estradiol-17beta. This would predicate an indirect role in the estradiol-17beta
      regulation of gonadotropin releasing hormone (GnRH) cells, since these receive
      input from the BNST. Ovariectomized ewes received 50 mug estradiol-17beta
      benzoate (i.m.) 1 h prior to brain collection, so that activated cells could be
      identified by Fos immunohistochemistry. Retrograde tracer (FluoroGold; FG), was
      injected into the three divisions of the BNST and labeled cells were mapped to
      the A1 and A2 regions and the parabrachial nucleus (PBN) of the brain stem. With
      FG injection into the dorsal and lateral BNST, all FG-containing cells in the
      caudal A1 and 45% of those in A2 stained for dopamine-beta-hydroxylase (DBH),
      indicating noradrenergic type. No FG-labelled cells in the PBN were DBH-positive.
      In A1 and A2 respectively, 42% and 46% of FG-labelled cells were Fos-positive,
      with no double-labeling in cells of the PBN. In ewes receiving FG injections into
      the ventral BNST, estrogen receptor (ER)alpha-immunoreactive nuclei were found in
      82% of A1-FG labeled and 38% of A2-FG labeled cells. No FG-labelled cells of the
      PBN were ERalpha-positive. Anterograde tracing from A1 with microruby injection
      identified projections to the PBN, BNST and preoptic area (POA). Thus, A1 and A2
      noradrenergic neurons project to the BNST in the ewe brain, express ERalpha and
      are activated by estradiol-17beta. These noradrenergic, estrogen-responsive cells
      may provide indirect input to GnRH cells, via the BNST.

PMID- 19857555
TI  - Downregulation of Kv4.2 channels mediated by NR2B-containing NMDA receptors in
      cultured hippocampal neurons.
AB  - Somatodendritic Kv4.2 channels mediate transient A-type potassium currents
      (I(A)), and play critical roles in controlling neuronal excitability and
      modulating synaptic plasticity. Our studies have shown an NMDA receptor-dependent
      downregulation of Kv4.2 and I(A). NMDA receptors are heteromeric complexes of NR1
      combined with NR2A-NR2D, mainly NR2A and NR2B. Here, we investigate NR2B receptor
      mediated modulation of Kv4.2 and I(A) in cultured hippocampal neurons.
      Application of glutamate caused a reduction in total Kv4.2 protein levels and
      Kv4.2 clusters, and produced a hyperpolarized shift in the inactivation curve of
      I(A). The effects of glutamate on Kv4.2 and I(A) were inhibited by pretreatment
      of NR2B-selective antagonists. NR2B-containing NMDA receptors are believed to be
      located predominantly extrasynaptically. Like application of glutamate, selective
      activation of extrasynaptic NMDA receptors caused a reduction in total Kv4.2
      protein levels and Kv4.2 clusters, which was also blocked by NR2B-selective
      antagonists. In contrast, specific stimulation of synaptic NMDA receptors had no
      effect on Kv4.2. In addition, the influx of Ca(2+) was essential for
      extrasynaptic modulation of Kv4.2. Calpain inhibitors prevented the reduction of
      total Kv4.2 protein levels following activation of extrasynaptic NMDA receptors.
      These results demonstrate that the glutamate-induced downregulation of Kv4.2 and
      I(A) is mediated by NR2B-containing NMDA receptors and is linked to proteolysis
      by calpain, which might contribute to the development of neuronal
      hyperexcitability and neurodegenerative diseases.

PMID- 19857556
TI  - Synphilin-1 exhibits trophic and protective effects against Rotenone toxicity.
AB  - Synphilin-1 is a cytoplasmic protein with unclear function. Synphilin-1 has been
      identified as an interaction partner of alpha-synuclein. The interaction between
      synphilin-1 and alpha-synuclein has implications in Parkinson's disease. In this
      study, we stably overexpressed human synphilin-1 in mouse N1E-115 neuroblastoma
      cells. We found that overexpression of synphilin-1 shortened cell growth doubling
      time and increased neurite outgrowth. Knockdown of endogenous synphilin-1 caused
      neuronal toxicity and shortened neurite outgrowth. We further found that
      synphilin-1 increased activation of the extracellular signal-regulated kinases
      (ERK1/2) and mediated neurite outgrowth. Rotenone, mitochondrial complex I
      inhibitor, has been shown previously to induce dopaminergic neurodegeneration and
      Parkinsonism in rats and Drosophila. We found that Rotenone induced apoptotic
      cell death in N1E-115 cells via caspase-3 activation and poly (ADP-ribose)
      polymerase (PARP) cleavage. Overexpression of synphilin-1 significantly reduced
      Rotenone-induced cell death, caspase-3 activation and PARP cleavage. The results
      indicate that synphilin-1 displays trophic and protective effects in vitro,
      suggesting that synphilin-1 may play a protective role in Parkinson's disease
      (PD) pathogenesis and may lead to a potential therapeutic target for PD
      intervention.

PMID- 19857557
TI  - Accumulation, functional annotation, and comparative analysis of expressed
      sequence tags in eggplant (Solanum melongena L.), the third pole of the genus
      Solanum species after tomato and potato.
AB  - Eggplant (Solanum melongena L.) is a widely grown vegetable crop that belongs to
      the genus Solanum, which is comprised of more than 1000 species of wide genetic
      and phenotypic variation. Unlike tomato and potato, Solanum crops that belong to
      subgenus Potatoe and have been targets for comprehensive genomic studies,
      eggplant is endemic to the Old World and belongs to a different subgenus,
      Leptostemonum, and therefore, would be a unique member for comparative molecular
      biology in Solanum. In this study, more than 60,000 eggplant cDNA clones from
      various tissues and treatments were sequenced from both the 5'- and 3'-ends, and
      a unigene set consisting of 16,245 unique sequences was constructed. Functional
      annotations based on sequence similarity to known plant reference datasets
      revealed a distribution of functional categories almost similar to that of
      tomato, while 1316 unigenes were suggested to be eggplant-specific. Sequence
      based comparative analysis using putative orthologous gene groups setup by
      reciprocal sequence comparison among six solanaceous species suggested that
      eggplant and its wild ally Solanum torvum were clustered separately from subgenus
      Potatoe species, and then, all Solanum species were clustered separately from the
      genus Capsicum. Microsatellite motif distribution was different among species and
      likely to be coincident with the phylogenetic relationships. Furthermore, the
      eggplant unigene dataset exhibited its utility in transcriptome analysis by the
      SAGE strategy where a considerable number of short tag sequences of interest were
      successfully assigned to unigenes and their functional annotations. The eggplant
      ESTs and 16k unigene set developed in this study would be a useful resource not
      only for molecular genetics and breeding in eggplant itself, but for expanding
      the scope of comparative biology in Solanum species.

PMID- 19857558
TI  - Molecular mechanisms of turtle anoxia tolerance: A role for NF-kappaB.
AB  - The transcription factor NF-kappaB has recently emerged as a central regulator of
      the vertebrate stress response, controlling hundreds of different effector genes.
      We hypothesized that this transcription factor would be activated during oxygen
      deprivation in the anoxia-tolerant freshwater turtle, Trachemys scripta elegans.
      Western immunoblotting was used to examine the relative expression levels of the
      phosphorylated NF-kappaB inhibitor, IkappaBalpha, under normoxic and anoxic
      conditions in turtle tissues. Elevated levels of the phosphorylated IkappaB were
      found in the liver in response to 5 h of anoxia, suggesting a possible activation
      of the NF-kappaB pathway. Analysis of the NF-kappaB subunits, p50 and p65, showed
      that both mRNA transcripts and protein levels of p50 increased during anoxia,
      whereas p65 protein levels also increased significantly. Changes in the relative
      levels of the NF-kappaB subunits in the nucleus, and changes in the DNA-binding
      activity of NF-kappaB were also assessed and were found to be elevated in
      response to anoxia. Finally, reverse-transcriptase PCR was used to measure mRNA
      transcript levels of selected downstream target genes under NF-kappaB control and
      these were elevated under anoxia. These findings show that the NF-kappaB pathway
      is activated in turtle liver during anoxia and support a role for this
      transcription factor in the anoxia tolerance of T. s. elegans.

PMID- 19857559
TI  - Deoxynivalenol and nivalenol inhibit lipopolysaccharide-induced nitric oxide
      production by mouse macrophage cells.
AB  - Deoxynivalenol (DON) and nivalenol (NIV), trichothecene mycotoxins, are secondary
      metabolites produced by Fusarium fungi. Trichothecene mycotoxins cause immune
      dysfunction, thus leading to diverse responses to infection. The present study
      evaluated the effect of DON and NIV on nitric oxide (NO) production by RAW264
      cells stimulated with lipopolysaccharide (LPS). LPS-induced NO production was
      reduced in the presence of these toxins. The transcriptional activation and
      expression of inducible NO synthase (iNOS) by LPS were also repressed by these
      toxins. DON or NIV inhibited LPS-induced expression of interferon-beta (IFN
      beta), which plays an indispensable role in LPS-induced iNOS expression. These
      results indicate that DON and NIV inhibit the LPS-induced NO and IFN-beta
      production, which both play an important role for host protection against
      invading pathogens, and suggests that the inhibition of these factors may be
      involved in the immunotoxic effects of these mycotoxins.

PMID- 19857561
TI  - Electrical impedance measurements of cochlear structures using the four-electrode
      reflection-coefficient technique.
AB  - In individuals with severe-to-profound hearing loss, cochlear implants (CIs)
      bypass normal inner ear function by applying electrical current directly into the
      cochlea, thereby stimulating surviving auditory nerve fibers. Although cochlear
      implants are able to restore some auditory sensation, they are far from providing
      normal hearing. It has been estimated that up to 75% of the current injected via
      a CI is shunted along scala tympani and is not available to stimulate auditory
      neurons. The path of the injected current and the consequent population of
      stimulated spiral ganglion cells are dependent upon the positions of the
      electrode contacts within the cochlea and the impedances of cochlear structures.
      However, characterization of the current path remains one of the most critical,
      yet least understood, aspects of cochlear implantation. In particular, the
      impedances of cochlear structures, including the modiolus, are either unknown or
      based upon estimates derived from circuit models. Impedance values for many
      cochlear structures have never been measured. By combining the hemicochlea
      preparation, a cochlea cut in half along its mid-modiolar plane, and the four
      electrode reflection-coefficient technique, impedances can be measured for
      cochlear tissues in a cochlear cross section including the modiolus. Advantages
      and disadvantages of the method are discussed in detail and electrical impedance
      measurements obtained in the gerbil hemicochlea are presented. The resistivity
      values for the cochlear wall in Omegacm are, 528 (range: 432-708) for scala media
      3rd turn, 502 (range: 421-616) for scala tympani 3rd turn and scala vestibuli 2nd
      turn, 627 (range: 531-759) for scala media 2nd turn, 434 (range: 353-555) for
      scala tympani 2nd turn and scala vestibuli basal turn, 434 (range: 373-514) for
      scala media basal turn, and 590 (range: 546-643) for scala tympani basal turn.
      The resistivity was 455Omegacm (range: 426-487) for the modiolus.

PMID- 19857560
TI  - The effect of midazolam on mouse Leydig cell steroidogenesis and apoptosis.
AB  - The peripheral-type benzodiazepine receptor (PBR), a putative receptor in Leydig
      cells, modulates steroidogenesis. Since benzodiazepines are commonly used in
      regional anesthesia, their peripheral effects need to be defined. Therefore, this
      study set out to investigate in vitro effects of the benzodiazepine midazolam
      (MDZ) on Leydig cell steroidogenesis, and the possible underlying mechanisms. The
      effects of MDZ on steroidogenesis in primary mouse Leydig cells and MA-10 Leydig
      tumor cells were determined by radioimmunoassay. PBR, P450scc, 3beta-HSD and StAR
      protein expression induced by MDZ was determined by Western blotting. Inhibitors
      of the signal transduction pathway and a MDZ antagonist were used to investigate
      the intracellular cascades activated by MDZ. In both cell types, MDZ-stimulated
      steroidogenesis in dose- and time-dependent manners, and induced the expression
      of PBR and StAR proteins, but had no effect on P450scc and 3beta-HSD expressions.
      Moreover, H89 (PKA inhibitor) and GF109203X (PKC inhibitor) attenuated MDZ
      stimulated steroid production. Interestingly, the MDZ antagonist (flumazenil) did
      not decrease MDZ-induced steroid production in both cell types. These results
      highly indicated that MDZ-induced steroidogenesis in mouse Leydig cells via PKA
      and PKC pathways, along with the expression of PBR and StAR proteins. In
      addition, MDZ at high dosages induced rounding-up, membrane blebbing, and then
      death in MA-10 cells. In conclusion, midazolam could induce Leydig tumor cell
      steroidogenesis, and high dose of midazolam could induce apoptosis in Leydig
      tumor cells.

PMID- 19857562
TI  - Neural substrate of sound duration discrimination during an auditory sequence in
      the guinea pig primary auditory cortex.
AB  - Mismatch negativity (MMN) is a negative component of event-related brain
      potentials elicited by stimulus transitions. Stimulus duration transition also
      elicits MMN (duration MMN), with a magnitude that is related to the degree of
      duration change and the discrimination ability. The neural substrates of duration
      MMN have not yet been investigated. We therefore studied how duration transitions
      in an auditory stimulus train are represented in neurons in the primary auditory
      cortex of anesthetized guinea pigs. Two types of neuronal responses to the
      context of changes in stimulus duration were found. One was a reduced response as
      the duration of the preceding stimulus was increased. Second was an enhancement
      of the late components of the response including sustained and offset responses
      at the duration transition. The former may be explained by the previously
      proposed two-tone suppression, which is dependent on the preceding stimulus
      duration. The latter is likely to be caused by stimulus-specific adaptation that
      could be a possible neural generator of duration MMN.

PMID- 19857563
TI  - Fertility inducing effect of aerial parts of Coccinia cordifolia L. in female
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The aerial parts of Coccinia cordifolia L. are
      used to treat female infertility in West Bengal state of India. AIM OF THE STUDY:
      The present study was undertaken to evaluate the fertility inducing effect of
      aerial parts of Coccinia cordifolia L. in female rats. MATERIALS AND METHODS: The
      effect of aqueous extract of Coccinia cordifolia L. on hyperprolactinemia induced
      infertility, endometriosis induced infertility and androgen-induced infertility
      was studied. The effect on serum estrogen level, serum progesterone level and
      reproductive tract was also evaluated in normal healthy female rats. The extract
      was administered orally at two different doses of 500 mg/kg and 1000 mg/kg.
      RESULTS: In hyperprolactinemia induced infertility model, the numbers of uterine
      implants were almost 10 times more in the extract treated groups as compared to
      control. The high dose of extract also produced a significant increase in serum
      estrogen levels (p<0.01) and number of corpus luteum (p<0.05) in healthy female
      rats. The extract at both doses was effective in reducing the weight of
      endometrial implants by 70-80%, but failed to induce fertility in rats with
      endometriosis. The extract was ineffective in inducing fertility in androgen
      induced infertility model. CONCLUSIONS: The aqueous extract of Coccinia
      cordifolia L. induces fertility in hyperprolactinemia induced infertility model
      in female rats.

PMID- 19857564
TI  - Appraisal of antinociceptive and anti-inflammatory potential of extract and
      fractions from the leaves of Torreya grandis Fort Ex. Lindl.
AB  - Torreya grandis (Taxaceae) was studied for antinociceptive and anti-inflammatory
      effects. Leaves were extracted with 80% ethanol at 80 degrees C for 3h and
      fractionated with petroleum ether, chloroform, ethylacetate and n-butanol. The
      aqueous ethanolic extract (aq.EE), ethylacetate fraction (EaF) and butanol
      fraction (BtF) at the doses of (100 and 200mg/kg, i.g.) body weight were used for
      study. Evaluation of antinociceptive activity was carried out by acetic acid
      induced writhing response and formalin-induced paw licking time in the first and
      second phases of mice. The paw edema induced by formalin- and xylene-induced ear
      edema were used to assess anti-inflammatory activity. It was found that Torreya
      grandis extract and fractions at the doses of (100 and 200mg/kg, i.g.) were
      significantly attenuated the writhing responses induced by acetic acid and second
      phase of pain response induced by subplantar injection of formalin in mice. In
      addition, these extract and fractions inhibiting the formaldehyde-induced
      arthritis as well as xylene-induces edema prolifically. From acute oral toxicity
      studies no mortality was pragmatic even at highest dose (2500 mg/kg, i.g.).
      Furthermore, our phytochemical studies indicated that the aq. ethanolic extract
      of leaves contains alkaloids, flavonoids, tannins, terpenoids and saponins. The
      results provide justification for the folkloric uses of Torreya grandis in the
      treatment of analgesic and inflammatory-based diseases across the China.

PMID- 19857565
TI  - The protective effects of Acanthopanax senticosus Harms aqueous extracts against
      oxidative stress: role of Nrf2 and antioxidant enzymes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (Rupr.et Maxim.) Harms,
      classified into the family of Araliaceae, is used in a variety of diseases in
      traditional Chinese system of medicine including hypertension, ischemic heart
      disease and hepatitis. MATERIALS AND METHODS: Different doses (75 mg/kg, 150
      mg/kg and 300 mg/kg) of aqueous extracts of Acanthopanax senticosus Harms were
      evaluated for the antioxidant activity against oxidative stress in mice induced
      by tert-butyl hydroperoxide (t-BHP) through observating histopathology of the
      liver and detecting antioxidant enzyme activity, concentration of antioxidant,
      and related gene and protein expression. RESULTS: Acanthopanax senticosus Harms
      aqueous extracts (ASE) attenuated the morphological injury of liver induced by t
      BHP and increased the activity of antioxidant enzymes and the ratio of GSH/GSSG
      in serum and liver homogenates. Medium and high doses of ASE also elevated the
      gene expression of NF-E2-related factor-2 (Nrf2), but not CuZnSOD, MnSOD,
      catalase (CAT), glutathione peroxidase (GPx) and GCLC. Protein expression results
      showed that Nrf2 and the antioxidant enzymes were all increased significantly by
      medium and high doses of ASE. CONCLUSION: The present results indicated that ASE
      protect against oxidative stress which may be generated via the induction of Nrf2
      and related antioxidant enzymes.

PMID- 19857566
TI  - Panaxatriol saponins extracted from Panax notoginseng induces thioredoxin-1 and
      prevents 1-methyl-4-phenylpyridinium ion-induced neurotoxicity.
AB  - AIM OF THE STUDY: Thioredoxin-1 has various biologic activities, including the
      control of redox balance and the inhibition of apoptosis. The current study was
      designed to examine the effects of panaxatriol saponins (PTS) extracted from
      Panax notoginseng on thioredoxin-1 expression and 1-methyl-4-phenylpyridinium ion
      induced injury. MATERIALS AND METHODS: Using PC12 cells and Kunming mice, we test
      thioredoxin-1 expression after PTS treatment by Western blot. The protective
      effect of PTS against 1-methyl-4-phenylpyridinium ion-induced injury was assessed
      by MTT assay and LDH release assay. RESULTS: PTS induced thioredoxin-1 expression
      in vitro and in vivo, and attenuated 1-methyl-4-phenylpyridinium ion-induced cell
      death of PC12 cells. CONCLUSIONS: PTS is a new inducer of thioredoxin-1 and has a
      possible potential as a therapeutic agent for neurodegenerative diseases
      including Parkinson's disease.

PMID- 19857567
TI  - Measuring depth of injury (DOI) in an isolated rabbit eye irritation test (IRE)
      using biomarkers of cell death and viability.
AB  - While DOI is a mechanistic correlate to the ocular irritation response, attempts
      to measure DOI in alternative tests have been limited to qualitative
      histopathologic assessment by veterinarian pathologists. The purpose of this
      study was to determine whether DOI could be measured objectively by fluorescent
      staining for biomarkers of cell death and viability using an ex vivo isolated
      rabbit eye (IRE) test. A panel of nine materials characterized by in vivo DOI
      were selected that caused slight (3% acetic acid and 5% SDS), mild (acetone,
      sodium hypochlorite and 10% acetic acid), moderate (cyclohexanol and
      parafluoroanaline) and severe (8% sodium hydroxide and 10% benzalkonium chloride)
      irritation. Materials were then tested using a modified IRE test with 3h recovery
      and then processed for cyrosectioning and staining using a TUNEL assay to detect
      cell death, phalloidin to detect intracellular f-actin and DAPI staining to
      detect nuclei. Control eyes treated with water showed intense phalloidin staining
      of the corneal epithelium and stromal keratocytes but no TUNEL labeling. In
      general, eyes treated with mild, moderate and severe irritants showed regions of
      TUNEL labeled epithelial and keratocyte nuclei with no phalloidin stain overlying
      phalloidin stained, undamaged cells. DOI measurements showed that slight
      irritants damaged<40% of the epithelium, mild and moderate irritants damaged>50%
      of the epithelium, extending at times into the anterior stroma (<20%), and the
      severe irritant damaged>50% of the stroma. Regression analysis between ex vivo
      and in vivo DOI showed a significant (p<0.007) correlation (r=0.785). These data
      suggest that fluorescent staining of fixed and sectioned tissue using biomarkers
      can be used to objectively identify the depth of injury caused by ocular
      irritants.

PMID- 19857568
TI  - Increased thrombin-induced polymerization of fibrinogen associated with high
      protein carbonyl levels in plasma from patients post myocardial infarction.
AB  - Increased levels of protein carbonyls have been measured in plasma of patients
      following a myocardial infarction (Mocatta et al. J. Am. Coll. Cardiol.49:1993
      2000; 2007). In this study, we have examined representative plasma samples from
      this group of patients. We show that carbonyls are formed preferentially on
      fibrinogen and that there is a strong correlation between fibrinogen and total
      plasma protein carbonyls. Functional properties of fibrinogen isolated from post
      myocardial plasmas were investigated by measuring thrombin-catalyzed
      polymerization. Fibrinogen from plasma with upper quartile protein carbonyls
      (mean 0.16 nmol/mg protein) polymerized approximately 1.4 times more rapidly and
      gave 1.4-fold higher maximum turbidity (12 per group, P<0.001) than fibrinogen
      from lower quartile carbonyl plasma (mean 0.007 nmol/mg), which behaved similarly
      to control plasma. Significant differences were also apparent when related to the
      carbonyl content of the fibrinogen itself. These changes in the high carbonyl
      plasma reflect a faster rate of lateral aggregation of small oligomers to form
      fibrin polymers that comprise thicker, more loosely woven fibers. In vivo this
      could be translated into a tendency to clot faster and form more fragile clots.
      High protein carbonyls in fibrinogen were not associated with an increased
      content of nitrotyrosine or chlorotyrosine. Nitrotyrosine levels were
      significantly lower in fibrinogen than total plasma protein, with no difference
      between patients and controls. Chlorotyrosine levels in fibrinogen (but not total
      protein) were significantly higher for the post myocardial patients. Our data
      suggest that high fibrinogen protein carbonyls in heart disease could be a
      prothrombotic risk factor.

PMID- 19857569
TI  - Activation of vascular endothelial nitric oxide synthase and heme oxygenase-1
      expression by electrophilic nitro-fatty acids.
AB  - Reactive oxygen species mediate a decrease in nitric oxide (NO) bioavailability
      and endothelial dysfunction, with secondary oxidized and nitrated by-products of
      these reactions contributing to the pathogenesis of numerous vascular diseases.
      While oxidized lipids and lipoproteins exacerbate inflammatory reactions in the
      vasculature, in stark contrast the nitration of polyunsaturated fatty acids and
      complex lipids yields electrophilic products that exhibit pluripotent anti
      inflammatory signaling capabilities acting via both cGMP-dependent and 
      independent mechanisms. Herein we report that nitro-oleic acid (OA-NO(2))
      treatment increases expression of endothelial nitric oxide synthase (eNOS) and
      heme oxygenase 1 (HO-1) in the vasculature, thus transducing vascular protective
      effects associated with enhanced NO production. Administration of OA-NO(2) via
      osmotic pump results in a significant increase in eNOS and HO-1 mRNA in mouse
      aortas. Moreover, HPLC-MS/MS analysis showed that NO(2)-FAs are rapidly
      metabolized in cultured endothelial cells (ECs) and treatment with NO(2)-FAs
      stimulated the phosphorylation of eNOS at Ser(1179). These posttranslational
      modifications of eNOS, in concert with elevated eNOS gene expression, contributed
      to an increase in endothelial NO production. In aggregate, OA-NO(2)-induced eNOS
      and HO-1 expression by vascular cells can induce beneficial effects on
      endothelial function and provide a new strategy for treating various vascular
      inflammatory and hypertensive disorders.

PMID- 19857570
TI  - Oxidants induce alternative splicing of alpha-synuclein: Implications for
      Parkinson's disease.
AB  - alpha-Synuclein (alpha-syn) is a presynaptic protein that is widely implicated in
      the pathophysiology of Parkinson's disease (PD). Emerging evidence indicates a
      strong correlation between alpha-syn aggregation and proteasomal dysfunction as
      one of the major pathways responsible for destruction of the dopamine neurons.
      Using parkinsonism mimetics (MPP(+), rotenone) and related oxidants, we have
      identified an oxidant-induced alternative splicing of alpha-syn mRNA, generating
      a shorter isoform of alpha-syn with deleted exon-5 (112-syn). This spliced
      isoform has an altered localization and profoundly inhibits proteasomal function.
      The generation of 112-syn was suppressed by constitutively active MEK-1 and
      enhanced by inhibition of the Erk-MAP kinase pathway. Overexpression of 112-syn
      exacerbated cell death in a human dopaminergic cell line compared to full-length
      protein. Expression of 112-syn and proteasomal dysfunction were also evident in
      the substantia nigra and to a lesser extent in striatum, but not in the cortex of
      MPTP-treated mice. We conclude that oxidant-induced alternative splicing of alpha
      syn plays a crucial role in the mechanism of dopamine neuron cell death and thus
      contributes to PD.

PMID- 19857571
TI  - Vacuolization and alterations of lysosomal membrane proteins in cochlear marginal
      cells contribute to hearing loss in neuraminidase 1-deficient mice.
AB  - The neuraminidase-1 (Neu1) knockout mouse model is a phenocopy of the lysosomal
      storage disease (LSD) sialidosis, characterized by multisystemic and neuropathic
      symptoms, including hearing loss. We have characterized the auditory defects in
      Neu1(-/-) mice and found that hearing loss involves both conductive and
      sensorineural components. Auditory brainstem response (ABR) thresholds were
      significantly elevated in Neu1(-/-) mice at P21 (48-55 dB), and hearing loss
      appeared progressive (53-66 dB at P60). At these ages Neu1(-/-) mice accumulated
      cerumen in the external ear canal and had a thickened mucosa and inflammation in
      the middle ear. In cochleae of adult wild-type mice, Neu1 was expressed in
      several cell types in the stria vascularis, the organ of Corti, and spiral
      ganglion. Progressive morphological abnormalities such as extensive vacuolization
      were detected in the Neu1(-/-) cochleae as early as P9. These early morphologic
      changes in Neu1(-/-) cochleae were associated with oversialylation of several
      lysosomal associated membrane proteins (Lamps) in the stria vascularis. A marked
      increase in the expression and apical localization of Lamp-1 in marginal cells of
      the stria vascularis predicts exacerbation of lysosomal exocytosis into the
      endolymph. Consequently, the endolymphatic potential in Neu1(-/-) mice was
      reduced by approximately 20 mV at ages P31-P44, which would cause dysfunction of
      transduction in sensory hair cells. This study suggests a molecular mechanism
      that contributes to hearing loss in sialidosis and identifies potential
      therapeutic targets.

PMID- 19857573
TI  - A single early postnatal estradiol injection affects morphology and gene
      expression of the ovary and parametrial adipose tissue in adult female rats.
AB  - Events during early life can affect reproductive and metabolic functions in
      adulthood. We evaluated the programming effects of a single early postnatal
      estradiol injection (within 3h after birth) in female rats. We assessed ovarian
      and parametrial adipose tissue morphology, evaluated gene expression related to
      follicular development and adipose tissue metabolism, and developed a non
      invasive volumetric estimation of parametrial adipose tissue by magnetic
      resonance imaging. Estradiol reduced ovarian weight, increased antral follicle
      size and number of atretic antral follicles, and decreased theca interna
      thickness in atretic antral follicles. Adult estradiol-injected rats also had
      malformed vaginal openings and lacked corpora lutea, confirming anovulation.
      Estradiol markedly reduced parametrial adipose tissue mass. Adipocyte size was
      unchanged, suggesting reduced adipocyte number. Parametrial adipose tissue
      lipoprotein lipase activity was increased. In ovaries, estradiol increased mRNA
      expression of adiponectin, complement component 3, estrogen receptor alpha, and
      glucose transporter 3 and 4; in parametrial adipose tissue, expression of
      complement component 3 was increased, expression of estrogen receptor alpha was
      decreased, and expression of leptin, lipoprotein lipase, and hormone-sensitive
      lipase was unaffected. These findings suggest that early postnatal estradiol
      exposure of female rats result in long-lasting effects on the ovary and
      parametrial adipose tissue at adult age.

PMID- 19857574
TI  - Interleukin-4 upregulates RhoA protein via an activation of STAT6 in cultured
      human bronchial smooth muscle cells.
AB  - Interleukin-4 (IL-4) is believed to play a role in allergic bronchial asthma, and
      has been suggested to cause hyperresponsiveness of airway smooth muscle. In the
      present study, the effects of IL-4 on the expression of RhoA protein, a monomeric
      GTP-binding protein that contributes to the contraction of smooth muscle, were
      determined in cultured human bronchial smooth muscle cells (hBSMCs). Incubation
      of hBSMCs with IL-4 (100ng/mL) caused a distinct phosphorylation of signal
      transducer and activator of transcription 6 (STAT6), a major signal transducer
      activated by IL-4, indicating that IL-4 is capable of activating signal
      transduction in the hBSMCs directly. IL-4 also caused a significant increase in
      the expression level of RhoA protein: the peak of the upregulation of RhoA
      protein was observed at 12-24h after the IL-4 treatment. Both the phosphorylation
      of STAT6 and the upregulation of RhoA protein induced by IL-4 were inhibited by
      the co-incubation with AS1517499, a selective inhibitor of STAT6, in a
      concentration-dependent fashion. These findings suggest that IL-4 is capable of
      inducing an upregulation of RhoA via an activation of STAT6 in cultured hBSMCs.
      The RhoA upregulation induced by IL-4, one of the Th2 cytokines upregulated in
      the airways of allergic bronchial asthmatics, might result in an augmentation of
      bronchial smooth muscle contractility, that is one of the causes of airway
      hyperresponsiveness.

PMID- 19857575
TI  - High-pressure freezing combined with in vivo-DAB-cytochemistry: a novel approach
      for studies of endocytic compartments.
AB  - Methods for fine structural and functional analyses of complex and dynamic cell
      compartments must ensure high temporal resolution together with an excellent fine
      structural preservation. High-pressure freezing followed by freeze-substitution,
      and resin embedding is state of the art but its use is limited in combination
      with preembedding cytochemical techniques. Here we show a new approach for the
      exploration of compartments of the endocytosis system, which combines high
      pressure freezing with peroxidase-catalyzed cytochemistry, thus using the
      potencies of both synergistically. Uptake of horseradish peroxidase-labeled
      molecules is followed by in vivo-staining and immobilization of endocytic
      compartments by generation of diaminobenzidine precipitates. Subsequently, the
      specimens are high pressure frozen, freeze-substituted, and embedded in resin.
      The excellent fine structural preservation, together with the high temporal
      resolution, and differentiating visualization of endocytic compartments qualify
      the new approach for morpho-functional studies of the complex and dynamic
      components of the endocytosis system involved in physiologic and pathologic
      cellular traffic, and in routes utilized in drug targeting strategies. The
      distinct appearances of membranes and reactive compartments provide optimal
      conditions for 3D-analyses by electron tomography allowing to discern subtle
      details of the complex 3D-structures of endocytic compartments.

PMID- 19857576
TI  - Comparative structural studies of two natural isoforms of ammodytoxin,
      phospholipases A2 from Vipera ammodytes ammodytes which differ in neurotoxicity
      and anticoagulant activity.
AB  - Ammodytoxin A (AtxA) and its natural isoform AtxC from the venom of Vipera
      ammodytes ammodytes belong to group IIA-secreted phospholipases A(2) which
      catalyze the hydrolysis of glycerophospholipids and exhibit strong neurotoxic and
      anticoagulant effects. The two isoforms, which differ in sequence by only two
      amino acid residues (Phe124>Ile and Lys128>Glu), display significant differences
      in toxicity and anticoagulant properties and act on protein targets including
      neurotoxic proteic receptors and coagulation factor Xa with significantly
      different strengths of binding. In order to characterize the structural basis of
      these functional differences, we have determined the crystal structures of the
      two isoforms. Comparison of the structures shows that the mutation Lys128>Glu in
      AtxC could perturb interactions with FXa, resulting in lower anticoagulant
      activity, since the side chain of Glu128 is partly buried, making a stabilizing
      hydrogen bond with the main-chain nitrogen atom of residue Thr35. This
      interaction leads to a displacement of the main polypeptide chain at positions
      127 and 128 (identified by mutagenesis as important for interaction with FXa),
      and a different orientation of the side chain of unmutated Lys127. The mutation
      Phe124>Ile in AtxC induces no significant conformational changes, suggesting that
      the differences in toxicity of the two isoforms are due essentially to
      differences in surface complementarity in the interaction of the toxin with the
      neurotoxic protein receptor. The crystal structures also reveal a novel dimeric
      quaternary association involving significant hydrophobic interactions between the
      N-terminal alpha-helices of two molecules of ammodytoxin related by
      crystallographic symmetry. Interactions at the dimer interface include important
      contributions from Met7, which is unique to ammodytoxin. Equilibrium
      sedimentation experiments are consistent with the crystallographic model.
      Competition experiments using SPR technology show complete inhibition of AtxA
      binding to FXa by calmodulin (CaM). The crystal structure shows that the C
      terminal region, important for binding to FXa and CaM, is fully exposed and
      accessible for interaction with proteic receptors in both the monomeric and
      dimeric forms of ammodytoxin described here.

PMID- 19857577
TI  - Evolution of the cerebellar cortex: the selective expansion of prefrontal
      projecting cerebellar lobules.
AB  - It has been suggested that interconnected brain areas evolve in tandem because
      evolutionary pressures act on complete functional systems rather than on
      individual brain areas. The cerebellar cortex has reciprocal connections with
      both the prefrontal cortex and motor cortex, forming independent loops with each.
      Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II
      connect with prefrontal cortex, whereas the primary motor cortex connects with
      cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species
      suggest that the prefrontal cortex has expanded more than cortical motor areas in
      human evolution. Given the enlargement of the prefrontal cortex relative to motor
      cortex in humans, our hypothesis would predict corresponding volumetric increases
      in the parts of the cerebellum connected to the prefrontal cortex, relative to
      cerebellar lobules connected to the motor cortex. We tested the hypothesis by
      comparing the volumes of cerebellar lobules in structural MRI scans in capuchins,
      chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and
      Crus II were significantly larger in humans compared to chimpanzees and
      capuchins. Our results therefore support the hypothesis that in the cortico
      cerebellar system, functionally related structures evolve in concert with each
      other. The evolutionary expansion of these prefrontal-projecting cerebellar
      territories might contribute to the evolution of the higher cognitive functions
      of humans.

PMID- 19857578
TI  - Fast and robust multi-atlas segmentation of brain magnetic resonance images.
AB  - We introduce an optimised pipeline for multi-atlas brain MRI segmentation. Both
      accuracy and speed of segmentation are considered. We study different similarity
      measures used in non-rigid registration. We show that intensity differences for
      intensity normalised images can be used instead of standard normalised mutual
      information in registration without compromising the accuracy but leading to
      threefold decrease in the computation time. We study and validate also different
      methods for atlas selection. Finally, we propose two new approaches for combining
      multi-atlas segmentation and intensity modelling based on segmentation using
      expectation maximisation (EM) and optimisation via graph cuts. The segmentation
      pipeline is evaluated with two data cohorts: IBSR data (N=18, six subcortial
      structures: thalamus, caudate, putamen, pallidum, hippocampus, amygdala) and ADNI
      data (N=60, hippocampus). The average similarity index between automatically and
      manually generated volumes was 0.849 (IBSR, six subcortical structures) and 0.880
      (ADNI, hippocampus). The correlation coefficient for hippocampal volumes was 0.95
      with the ADNI data. The computation time using a standard multicore PC computer
      was about 3-4 min. Our results compare favourably with other recently published
      results.

PMID- 19857579
TI  - Incongruence between molecular phylogeny and morphological classification in
      amphipod crustaceans: a case study of Antarctic lysianassoids.
AB  - In Antarctic waters, the superfamily Lysianassoidea is one of the most important
      amphipod groups both in terms of species number and abundance. Dominant members
      of this superfamily are species of the orchomenid complex, found throughout the
      Southern Ocean. This study presents the first molecular phylogenetic analysis
      based on a representative subset of the Antarctic species belonging to different
      orchomenid genera and hence provides a framework for a systematic revision of
      these taxa. The current classification of the orchomenid genera is mainly based
      on mouthpart morphology. The validity of these morphological characters was
      assessed by resolving phylogenetic relationships using nuclear 28S rRNA and
      mitochondrial cytochrome oxidase subunit I sequences. The molecular data rejected
      most of the previously proposed taxonomic subdivisions within this complex. The
      genera Abyssorchomene and Orchomenella as well as the subgenus Orchomenopsis
      appeared to be non-monophyletic. This implies that the supposed diagnostic
      characters are likely a result of convergent evolution. Further, our results
      indicated the necessity of a revision of the family-level systematics.

PMID- 19857580
TI  - Multiple patterns of rDNA evolution following polyploidy in Oryza.
AB  - Ribosomal ITS sequences are commonly used for phylogenetic reconstruction because
      they are included in rDNA repeats, and hence are ubiquitous and present in high
      copy number. Ribosomal rDNA repeats often undergo rapid concerted evolution
      within and between arrays. Interspecific hybridization merges divergent repeat
      types in a single nucleus, setting in motion evolutionary processes leading to
      coexistence, maintenance of paralogs, origin of novel sequence variants, loss of
      arrays, or inter-array sequence homogenization via concerted evolution. Here we
      examined ITS polymorphism within and among six Oryza tetraploids of varying
      genomic composition to infer the extent and direction of concerted evolution
      following allopolyploid speciation. We demonstrate that different polyploids have
      experienced varying fates, including maintenance or homogenization of divergent
      arrays, even among allopolyploids having the same genomic origins but in
      different geographic locations. Bidirectional concerted evolution, in which
      arrays become homogenized to alternative progenitor diploid types in different
      allopolyploid derivatives, is evident among species in one clade. Our results
      exemplify the panoply of outcomes for ribosomal DNA evolution following
      allopolyploid speciation.

PMID- 19857581
TI  - Effects of acute stress and GluN2B-containing NMDA receptor antagonism on object
      and object-place recognition memory.
AB  - The mechanisms underlying the complex effects of acute stress on memory are
      incompletely understood. Previous work suggests that the activation of N-methyl-d
      aspartate (NMDA) receptors specifically containing GluN2B subunits may underlie
      the disruptions in spatial memory retrieval caused by acute stress (Wong et al.,
      2007 PNAS 104:11471). The present experiments were designed to assess whether a
      similar mechanism is involved in recognition memory. Recognition memory retrieval
      was assessed in Sprague-Dawley rats using an object recognition test and an
      object-place recognition test, both of which rely on patterns of spontaneous
      exploration. Exposure to acute stress for 30 min immediately before the test
      phase of either test disrupted memory retrieval. Administration of the GluN2B
      selective antagonist Ro25-6981 (6 mg/kg; i.p.) enhanced memory in the object
      recognition test regardless of whether animals were exposed to acute stress. In
      the object-place test, Ro25-6981 had no effect on memory retrieval in the absence
      of stress but promoted memory following acute stress. These data highlight the
      specific contributions made by GluN2B-containing NMDA receptors to recognition
      memory for different types of stimuli.

PMID- 19857582
TI  - Vasopressin/oxytocin-related peptides influence long-term memory of a passive
      avoidance task in the cuttlefish, Sepia officinalis.
AB  - The vasopressin (VP)/oxytocin (OT)-related peptides constitute a large
      superfamily found in a wide range of both vertebrate and invertebrate species.
      While intensive literature reports that these neuropeptides influence behavior,
      especially learning and memory, in numerous species from diverse vertebrate
      groups, their roles in behavioral regulation have never been studied in
      invertebrates. Here, we investigated the role of two VP/OT superfamily peptides,
      octopressin (OP) and cephalotocin (CT), on long-term memory (LTM) formation of a
      passive avoidance task in a cephalopod mollusc, the cuttlefish, Sepia
      officinalis. Subadult cuttlefish were intravenously injected, in a dose range of
      3-60 microg/kg, 1h after the training phase (consolidation design); retention
      performance was tested 24h post-training. We found that administration of OP at
      low dose (3 microg/kg) enhanced LTM, whereas a dose of 60 microg/kg attenuated
      it. No effect of OP on LTM was observed for the 15 microg/kg dose. Conversely, an
      enhancement of retention performance was observed at all doses of CT tested. This
      study is the first to demonstrate the behavioral effects of VP/OT superfamily
      peptides in an invertebrate species. The valuable role of VP/OT-like peptides on
      memory processes offers new evolutionary perspectives on peptidergic transmission
      and neuromodulation.

PMID- 19857583
TI  - Reacquisition of heroin and cocaine place preference involves a memory
      consolidation process sensitive to systemic and intra-ventral tegmental area
      naloxone.
AB  - To investigate the effect of naloxone on a putative memory consolidation process
      underlying reacquisition of heroin and cocaine conditioned place preference, four
      studies were conducted in male Sprague-Dawley rats using a common procedure
      involving: place conditioning (0.3 or 1mg/kg heroin or 20mg/kg cocaine; x4
      sessions), extinction (vehiclex4 sessions), and reconditioning (0 or 1mg/kg
      heroin or 20mg/kg cocaine; x1 session). Systemic naloxone injections (0, 1 and
      3mg/kg) or bilateral intra-ventral tegmental area (VTA) naloxone methiodide
      infusions (2 nmol in 0.5 microl x side) were administered at different times
      following reconditioning. Post-reconditioning administration of naloxone dose
      dependently blocked, attenuated and had no effect on reacquisition of heroin CPP
      when administered immediately, 1h and 6h after reconditioning, respectively. The
      highest dose of naloxone also blocked reacquisition of cocaine CPP, and did not
      produce a conditioned place aversion in heroin-naive and heroin pre-treated
      animals. Post-reconditioning infusions in the VTA, but not in adjacent
      structures, blocked reacquisition of heroin CPP when administered immediately,
      but not 6h, after reconditioning. These data suggest that reacquisition of drug
      cues associations involves a memory consolidation process sensitive to
      manipulations of the endogenous opioid system, and indicate that opioid receptors
      in the VTA may be critically involved in the re-emergence of drug seeking
      behavior.

PMID- 19857584
TI  - Should methotrexate plus calcineurin inhibitors be considered standard of care
      for prophylaxis of acute graft-versus-host disease?
AB  - In a rapidly developing field, one can always anticipate that different
      interpretations of similar data will coexist. Stem cell transplanters can be a
      contentious lot, especially in the absence of controlled randomized trials. Thus,
      although improvements in the basic understanding of acute graft-versus-host
      disease (aGVHD) has led to many testable hypotheses in the management of GVHD,
      there remains little consensus regarding the most effective and least toxic
      approach to GVHD prevention. In the 1980s, the comparison would have been between
      cyclosporine-based regimens and ex vivo T cell depletion (TCD). Although ex vivo
      TCD is still used in some settings, pharmacologic-based therapy and in vivo TCD
      with serotherapy now predominate. This review is meant to highlight the
      advantages and disadvantages of the "standard of care" and assess the prospects
      for future regimens that may be more effective.

PMID- 19857585
TI  - Therapy-related myelodysplastic syndrome: models and genetics.

PMID- 19857586
TI  - Myelodysplastic syndromes: from neglect to prominence.

PMID- 19857587
TI  - The role of missing killer cell immunoglobulin-like receptor ligands in T cell
      replete peripheral blood stem cell transplantation from HLA-identical siblings.
AB  - The contribution of natural killer (NK) cells to graft-versus-malignancy (GVM)
      effects following hematopoietic stem cell transplantation (HSCT) remains
      uncertain, particularly in the HLA-identical setting. A model considering missing
      HLA ligands to the donor's inhibitory killer cell immunoglobulin-like receptor
      (KIR), termed the missing KIR ligand model, has been established in T cell
      depleted bone marrow transplantation (BMT), but lacks validity in other cohorts
      with different treatment characteristics. We hypothesized that the impact of
      missing KIR ligands on relapse-free survival (RFS) and overall survival (OS) in T
      cell replete peripheral blood SCT (PBSCT) differs from that in the T cell
      depleted BMT setting, and retrospectively evaluated 100 consecutive, HLA
      identical sibling transplantations for hematologic malignancies. In addition to
      KIR ligand status, we considered the donors' activating KIRs and grafted NK, T,
      and CD34(+) cell doses. Our findings demonstrate noninferiority for OS (P = .005)
      and RFS (P = .002) for the heterozygous HLA-C group KIR ligand status (C1/2; n =
      47) compared with patients missing either C1 or C2 (n = 53). Similarly, OS (P =
      .031) and RFS (P = .034) of Bw4-positive patients was noninferior to that of
      patients missing a Bw4 ligand to KIR3DL1. By multivariate analysis, C1/2
      heterozygous patients had a favorable risk ratio (RR) for relapse (RR = 0.28; P =
      .003), RFS (RR = 0.56; P = .046), and acute graft-versus-host disease grade II-IV
      (RR = 0.36; P = .05). Following reduced-intensity conditioning (RIC), but not
      standard-intensity conditioning, myeloablative (MA) transplantation, a grafted NK
      cell dose above the median (3.4 x 10(7)/kg) was associated with a lower risk of
      relapse (RR = 0.57; P = .003) and improved survival (RR = 0.78; P = .03).
      Overall, our findings support a role for NK alloreactivity in HLA-identical HSCT,
      but argue against a favorable impact of missing KIR ligands in the given setting.
      We conclude that the mechanism favoring the missing KIR ligand constellation in T
      cell depleted BMT may not operate in T cell replete PBSCT. The reasons for this
      differential effect remain unresolved.

PMID- 19857588
TI  - Relapse after allogeneic hematopoietic cell therapy.
AB  - Disease relapse remains a major cause of mortality following allogeneic
      hematopoietic cell transplantation (HCT). Over the past decade, our understanding
      of the biology underlying the graft-versus-tumor/leukemia (GVT) effect has
      increased greatly; however, several other factors affect the occurrence and
      outcome of relapse, including conditioning regimen, type of allograft, and the
      histology, status, and sensitivity to chemotherapy of the disease being treated.
      The mainstay of relapse treatment is donor lymphocyte infusion (DLI), but the
      efficacy of DLI is quite variable depending on disease histology and state. As
      such, there is a significant need for novel therapies and strategies for relapse
      following allogeneic HCT, particularly in patients for whom DLI is not an option.
      The National Cancer Institute is sponsoring an international workshop to address
      issues and research questions relative to the biology, natural history,
      prevention, and treatment of relapse following allogeneic HCT.

PMID- 19857589
TI  - Hematopoietic stem cell transplantation for myelodysplastic syndrome.
AB  - Allogeneic hematopoietic stem cell transplantation remains the only curative
      option for myelodysplastic syndrome, but patients with this disease are often
      older and frail, and treatment-related mortality and morbidity is a major
      obstacle to be overcome. Treatment of MDS is likely to benefit from the major
      lines of investigation in the field of allogeneic transplantation, especially
      interventions postulated to decrease the morbidity of the procedure, such as less
      toxic preparative regimens. In this review we summarize current recommendations
      and controversies surrounding HSCT as well as integration of the novel
      therapeutic agents in the peritransplant period.

PMID- 19857590
TI  - Pre-engraftment syndrome after double-unit cord blood transplantation: a distinct
      syndrome not associated with acute graft-versus-host disease.
AB  - Pre-engraftment syndrome (PES) occurring after cord blood transplantation (CBT)
      is poorly characterized. We reviewed 52 consecutive double-unit CBT recipients
      treated for high-risk hematologic malignancies. PES was defined as unexplained
      fever >38.3 degrees C (101 degrees F) not associated with infection and
      unresponsive to antimicrobials, and/or unexplained rash occurring before or at
      neutrophil recovery. CBT recipients (median age, 38 years; range, 3-66 years)
      received either myeloablative (MA; n=36) or nonmyeloablative (NMA; n=16)
      conditioning. Sixteen patients (31%) fulfilled PES criteria: 15 with fever
      (median at onset, 39 degrees C [102.2 degrees F]), 13 of whom also had rash, and
      1 with rash alone. The median onset was 9 days (range, 5-12 days)
      posttransplantation (a median of 14 days before neutrophil recovery). Sixteen
      patients (14 with PES and 2 with infection and possible PES) received intravenous
      methylprednisolone (median dose, 1mg/kg; median duration, 3 days); 15 (94%)
      experienced resolution of fever within 24 hours. Recurrent PES (n=3) resolved
      with retreatment. There was no association between the development of PES and the
      likelihood of sustained donor engraftment, speed of neutrophil recovery, grade II
      IV acute graft-versus-host disease (aGVHD), day-180 treatment-related mortality
      (TRM), or survival. PES is common after CBT, precedes neutrophil recovery, is
      distinct from and does not predict for aGVHD, and responds promptly to short
      course corticosteroid therapy.

PMID- 19857591
TI  - How to treat MDS without stem cell transplantation.
AB  - Although allogeneic hematopoietic cell transplantation (HCT) is the only proven
      curative treatment for myelodysplastic syndromes (MDS), it is only used to treat
      a minority of MDS patients. The majority of patients are too old or suffer from
      comorbidities rendering allogeneic HCT too risky. Alternative treatment
      strategies for patients with higher risk MDS try to alter the natural course of
      disease by preventing or delaying leukemic transformation. In patients with lower
      risk MDS, treatment is mainly focused on maintaining or improving the quality of
      life.

PMID- 19857592
TI  - Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour
      progression.
AB  - Tumours are highly complex tissues composed of carcinoma cells and surrounding
      stroma, which is constructed by various different types of mesenchymal cells and
      an extracellular matrix (ECM). Carcinoma-associated fibroblasts (CAFs), which
      consist of both fibroblasts and myofibroblasts, are frequently observed in the
      stroma of human carcinomas, and their presence in large numbers is often
      associated with the development of high-grade malignancies and poor prognoses.
      Moreover, in human tumour xenograft models, CAFs extracted from the tumour are
      more capable of promoting tumour growth through their interactions with carcinoma
      cells when compared to those isolated from non-cancerous stroma. Taken together,
      these observations strongly suggest that CAFs actively contribute to tumour
      progression. In this review we highlight the emerging roles of these cells in
      promoting tumourigenesis, and we discuss the molecular mechanisms underlying
      their tumour-promoting capabilities and their cellular origin.

PMID- 19857593
TI  - Stroma in breast development and disease.
AB  - It is increasingly apparent that normal and malignant breast tissues require
      complex local and systemic stromal interactions for development and progression.
      During development, mammary cell fate specification and differentiation require
      highly regulated contextual signals derived from the stroma. Likewise, during
      breast carcinoma development, the tissue stroma can provide tumor suppressing and
      tumor-promoting environments that serve to regulate neoplastic growth of the
      epithelium. This review focuses on the role of the stroma as a mediator of normal
      mammary development, as well as a critical regulator of malignant conversion and
      progression in breast cancer. Recognition of the important role of the stroma
      during the progression of breast cancers leads to the possibility of new targets
      for treatment of the initial breast cancer lesion as well as prevention of
      recurrence.

PMID- 19857595
TI  - The cost of ventilation in birds measured via unidirectional artificial
      ventilation.
AB  - The highly derived mechanism birds use to ventilate their lungs relies on
      dorsoventral excursions of their heavily muscled sternum and abdominal viscera.
      Our expectation of the level of mechanical work involved in this mechanism led us
      to hypothesize that the metabolic cost of breathing is higher in birds than in
      other tetrapods. To test this theory, we used unidirectional artificial
      ventilation (UDV) to stop normal ventilatory movements in guinea fowl (Numida
      meleagris L.) at rest and during treadmill locomotion at three speeds. Oxygen
      consumption was measured during normal breathing and UDV, and the difference was
      used to approximate the cost of ventilation. Contrary to our prediction,
      metabolism increased when ventilatory movements ceased during UDV at rest.
      Although we do not understand why this occurred we suspect that UDV induced a
      homeostatic mechanism to counteract the loss of carbon dioxide. Nevertheless,
      across all running speeds, metabolism decreased significantly with UDV,
      indicating a minimum cost of ventilation during running of 1.43+/-0.62% of total
      running metabolism or 0.48+/-0.21 mL O(2) (L ventilated)(-1). These results
      suggest that the metabolic cost of ventilation is low in birds and that it is
      within the range of costs reported previously for other amniotes.

PMID- 19857596
TI  - Photoperiod-induced differences in uterine growth in Phodopus sungorus are
      evident at an early age when serum estradiol and uterine estrogen receptor levels
      are not different.
AB  - Sexual development is inhibited in Siberian hamsters (Phodopus sungorus) in short
      days (SD), and a small uterus is an obvious indicator of photo-inhibition. The
      small uterus in SD is presumably due to the delayed onset of estrous cycles.
      However, in an earlier study, the investigators reported that serum estradiol
      (E2) concentration was significantly higher in young females raised in SD than in
      long days (LD), with the highest concentrations measured in SD at 4 weeks of age.
      These seemingly contradictory findings were investigated in the present study.
      First, uterine mass and body mass were measured in SD- and LD-reared hamsters
      from 1 to 12 weeks of age. Uterine mass was significantly greater in LD than in
      SD by 3 weeks of age and onward. Thereafter, our investigation focused on 4-week
      old hamsters. Serum E2 concentrations in LD and in SD were not significantly
      different and there were no significant LD-SD differences in uterine estrogen
      receptors (ER), as measured by immunohistochemistry and quantitative real-time RT
      PCR. Therefore, alternative explanations for the photoperiodic difference in
      uterine size in young Siberian hamsters are considered.

PMID- 19857594
TI  - Fungal PDR transporters: Phylogeny, topology, motifs and function.
AB  - The overexpression of pleiotropic drug resistance (PDR) efflux pumps of the ATP
      binding cassette (ABC) transporter superfamily frequently correlates with
      multidrug resistance. Phylogenetic analysis of 349 full-size ( approximately
      160kDa) PDR proteins (Pdrps) from 55 fungal species, including major fungal
      pathogens, identified nine separate protein clusters (A-G, H1a/H1b and H2).
      Fungal, plant and human ABCG-family Pdrps possess a nucleotide-binding domain
      [NBD] and a transmembrane domain [TMD] in a family-defining 'reverse' ABC
      transporter topology [NBD-TMD] that is duplicated [NBD-TMD](2) in full-size
      fungal and plant Pdrps. Although full-size Pdrps have similar halves indicating
      early gene duplication/fusion, they show asymmetry of their NBDs and
      extracellular loops (ELs). Members of cluster F are most symmetric and may be
      closely related to the evolutionary ancestor of Pdrps. Unique structural elements
      are predicted, new PDR-specific motifs identified, and the significance of these
      and other structural features discussed.

PMID- 19857598
TI  - A bombesin-like peptide from skin of Sanguirana varians.
AB  - Bombesin-like peptides (BLPs) are a family of neuro-endocrinic peptides that
      mediates a variety of biological activities. A BLP named bombesin-SV from the
      skin secretions of the frog, Sanguirana varians, was purified and characterized.
      Its amino acid sequence is pEMIFGAPMWALGHLM-NH2 determined by Edman degradation
      and mass spectrometry. The cDNA encoding bombesin-SV precursor was cloned from
      skin cDNA library of S. varians. The precursor is composed of 67 amino acid
      residues including a copy of mature bombesin-SV. Two predicted enzymatic
      processing sites (-Lys-Arg-) are flanked at the mature bombesin-SV sequence. In
      the in vitro myotropic contraction experiment, the synthesized bombesin-SV
      displayed the stimulating effect toward rat stomach strips, suggesting that
      bombesin-SV acts as agonist as most other BLPs do.

PMID- 19857597
TI  - Intracellular pH regulation in isolated trout gill mitochondrion-rich (MR) cell
      subtypes: evidence for Na+/H+ activity.
AB  - We have studied intracellular pH (pH(i)) recovery in isolated trout gill
      mitochondrion-rich (MR) cells following acidification by the NH(4)Cl pre-pulse
      technique. Within a mixed MR cell population, one cell type displayed Na(+)
      independent pH(i) recovery while the other cell type lacked a Na(+)-independent
      pH(i) recovery. Cells displaying Na(+) independent recovery exhibited a
      significantly higher buffering capacity compared to cells lacking Na(+)
      independent pH(i) recovery. Cells displaying Na(+) independent recovery were
      identified as PNA(+) (peanut lectin agluttinin binding) MR cells while those
      unable to recover were identified as PNA(-) (non-peanut lectin agluttinin
      binding) MR cells. Therefore, recovery from acidification in the absence of Na(+)
      provides a direct functional marker for PNA(+) and PNA(-) MR cells. Re-addition
      of Na(+) to acidified cells resulted in a transient pH(i) recovery in both cell
      types. This event was abolished by amiloride (500 microM) but it was insensitive
      to phenamil (50 microM). The phorbol ester PMA (1 microM) potentiated the Na(+)
      induced pH(i) recovery suggesting that activation by PKC is required for
      continuous Na(+)/H(+) exchanger activity in trout gill MR cells. This study is
      the first functional description of pH(i) recovery in lectin-identified trout
      gill MR cells and provides insight into a putative cellular signaling mechanism
      that may control pH(i) regulation in the gill epithelium.

PMID- 19857599
TI  - Interferon regulatory factor-2 in orange-spotted grouper (Epinephelus coioides):
      gene, inductive expression pattern and subcellular localization.
AB  - Interferon regulatory factor 2 (IRF-2) is a multifunctional transcription factor
      which exhibits both transcriptional activating and repressing activities in the
      IRF family. In this study, we report an IRF-2 gene isolated from orange-spotted
      grouper (Epinephelus coioides). The 1854bp full-length cDNA sequence of EcIRF-2
      has been cloned, encoding a putative peptide of 336 amino acids which is highly
      consistent with the feature of IRF family members. The genomic fragment of EcIRF
      2 contains nine exons and eight introns, spanning over approximate 8.8kb. The
      expression of EcIRF-2 gene was detected in various tissues of healthy orange
      spotted grouper and in four tissues after being challenged with poly I:C or LPS.
      EcIRF-2 gene is ubiquitously expressed in various healthy fish tissues and is up
      regulated in vivo in response to poly I:C or LPS. Subcellular localization
      analysis of EcIRF-2 suggests it is an intranuclear protein in the fish cells. We
      believe this research is the first report of fish IRF-2 protein localization. The
      results in this research establish the base for further study of function
      mechanism of IRF family members in orange-spotted grouper.

PMID- 19857600
TI  - Improved detection of intact tyrosine sulfate-containing peptides by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry in linear
      negative ion mode.
AB  - Sulfation of tyrosine residues is a common post-translational modification, but
      detecting and quantitating this modification poses challenges due to lability of
      the sulfate group. The goal of our studies was to determine how best to detect
      and to assess the stoichiometry of this modification using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). Sulfated
      and nonsulfated forms of peptides-hirudin(55-65), caerulein, and cholecystokinin
      octapeptide and phosphorylated and nonphosphorylated pp60-c-src (521-533)-were
      analyzed using several matrices: sinapinic acid (SA), 2,5-dihydroxybenzoic acid
      (DBA), and cyano-4-hydroxycinnamic acid (CHCA). Intact sulfated peptides were
      difficult to detect using positive ion mode; peptides were observed as desulfated
      ions. Phosphorylated peptide was stable and was detected in positive and negative
      ion modes. Detection of sulfated peptides improved with: (1) Analysis in negative
      ion mode, (2) Decreased laser power, (3) Matrix selection: DBA>/=SA>CHCA. In
      negative ion mode, desorption/ionization of sulfated peptide was equivalent or
      more efficient than nonsulfated peptide, depending on conditions of analysis.
      Examination of a tryptic digest of alpha(2)-antiplasmin detected the single site
      of sulfation in negative ion mode but not in positive ion mode. We conclude that
      improved detection of sulfated peptides can be achieved in negative ion mode.
      Dual analysis in positive and negative ion modes serves as a potential means of
      identifying peptides with labile modifications such as sulfation and
      distinguishing them from phosphorylation.

PMID- 19857601
TI  - Ischemia-reperfusion alters cardiac lipoprotein lipase.
AB  - Ischemia-reperfusion (I/R) is associated with changes in energy metabolism in the
      heart. However, the majority of studies have focused on examining rates and
      extent of fatty acid (FA) oxidation, with limited emphasis on FA delivery. We
      examined the influence of acute myocardial I/R on coronary lipoprotein lipase
      (LPL), the key enzyme responsible for triglyceride-lipoprotein hydrolysis and FA
      delivery to the heart. In a whole animal and an ex vivo model of I/R, we
      demonstrate increases in luminal LPL activity, an effect that involved signaling
      through nitric oxide. Given the damaging effect of excess FA utilization by the
      ischemic heart, strategies to restrict LPL at the vascular lumen would be an
      attractive therapeutic option in limiting I/R related cardiac injury.

PMID- 19857602
TI  - Remodeling of phosphatidylglycerol in Synechocystis PCC6803.
AB  - The phosphatidylglycerol deficient DeltapgsA mutant of Synechocystis PCC6803
      provided a unique experimental system for investigating in vivo retailoring of
      exogenously added dioleoylphosphatidylglycerol in phosphatidylglycerol-depleted
      cells. Gas chromatographic analysis of fatty acid composition suggested that
      diacyl-phosphatidylglycerols were synthesized from the artificial synthetic
      precursor. The formation of new, retailored lipid species was confirmed by
      negative-ion electrospray ionization-Fourier-transform ion cyclotron resonance
      and ion trap tandem mass spectrometry. Various isomeric diacyl
      phosphatidylglycerols were identified indicating transesterification of the
      exogenously added dioleoylphosphatidyl-glycerol at the sn-1 or sn-2 positions.
      Polyunsaturated fatty acids were incorporated selectively into the sn-1 position.
      Our experiments with Synechocystis PCC6803/DeltapgsA mutant cells demonstrated
      lipid remodeling in a prokaryotic photosynthetic bacterium. Our data suggest that
      the remodeling of diacylphosphatidylglycerol likely involves reactions catalyzed
      by phospholipase A(1) and A(2) or acyl-hydrolase, lysophosphatidylglycerol
      acyltransferase and acyl-lipid desaturases.

PMID- 19857603
TI  - Fatty liver and lipotoxicity.
AB  - Fatty liver disease comprises a spectrum ranging from simple steatosis to
      steatohepatitis which can progress to liver cirrhosis and hepatocellular cancer.
      Hepatic lipotoxicity may ensue when the hepatic capacity to utilize, store and
      export fatty acids (FA) as triglycerides is overwhelmed. Additional mechanisms of
      hepatic lipotoxicity include abnormal FA oxidation with formation of reactive
      oxygen species, disturbances in cellular membrane FA and phospholipid
      composition, alterations of cholesterol content and ceramide signalling.
      Lipotoxicity is a key factor for the progression of fatty liver disease by
      inducing hepatocellular death, activating Kupffer cells and an inflammatory
      response, impairing hepatic insulin signalling resulting in insulin resistance,
      and activation of a fibrogenic response in hepatic stellate cells that can
      ultimately lead to cirrhosis. Therefore, the concept of hepatic lipotoxicity
      should be considered in future therapeutic concepts for fatty liver disease.

PMID- 19857604
TI  - Thyroid hormone and myocardial mitochondrial biogenesis.
AB  - Mitochondria have been central in the development of some of the most important
      ideas in modern biology. Since the discovery that mitochondria have its own DNA
      and specific mutations and deletions were found in association with neuromuscular
      and heart diseases, as well as in aging, an extraordinary number of publications
      have followed, and the term mitochondrial medicine was coined. Recently, it has
      been found that thyroid hormone (TH) stimulates cardiac mitochondrial biogenesis
      increasing myocardial mitochondrial mass, mitochondrial respiration, oxidative
      phosphorylation (OXPHOS), enzyme activities, mitochondrial protein synthesis (by
      stimulation in a T3-dependent manner), cytochrome, phospholipid and mtDNA
      content. Also, TH therapy may modulate cardiac mitochondrial protein-import
      apparatus. To identify the sequence of events, molecules and signaling pathways
      that is activated by TH affecting mitochondrial structure, biogenesis and
      function further research is warranted.

PMID- 19857605
TI  - The crosstalk between thyroid hormones and the Renin-Angiotensin System.
AB  - Thyroid hormones (THs) exert multiple effects on the heart and vascular system.
      As a consequence, altered cardiovascular function observed in the thyroid
      diseases corresponds to one of the most important and clinically relevant aspects
      found in both hyperthyroidism and hypothyroidism. Besides THs' direct effects on
      the heart and vascular system, in the last three decades several studies have
      implicated the Renin-Angiotensin System (RAS) in some of the cardiovascular
      effects of THs, with this interaction suggesting that RAS may be an important
      mediator of THs actions. In the present review, we discuss the alterations in the
      circulating RAS, as well as modifications in cardiac and vascular RAS which are
      involved in the cardiovascular alterations found during the modulation of TH
      levels. In addition, considering the important role that both systems present
      during fetal and neonatal periods, we also review the interaction between THs and
      the RAS in the development of cardiovascular system. A greater understanding of
      the role of the RAS in hyperthyroidism and hypothyroidism, during early or adult
      life will presumably facilitate the evolution of newer, targeted therapies.

PMID- 19857606
TI  - Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery.
AB  - Poor ocular bioavailability of drugs (<1%) from conventional eye drops (ie,
      solution, suspension, and ointments) is mainly due to the physiologic barriers of
      the eye. In general, ocular efficacy is closely related to ocular drug
      bioavailability, which may be enhanced by increasing corneal drug penetration and
      prolonging precorneal drug residence time. In our current work, we develop and
      evaluate a new colloidal system, that is, poly(dl-lactide-co-glycolide) (PLGA)
      nanoparticles for sparfloxacin ophthalmic delivery, to improve precorneal
      residence time and ocular penetration. Nanoparticles were prepared by
      nanoprecipitation technique and characterized for various properties such as
      particle size, zeta potential, in vitro drug release, statistical model fitting,
      stability, and so forth. Microbiological assay was carried out against
      Pseudomonas aeruginosa using the cup-plate method. Precorneal residence time was
      studied in albino rabbits by gamma scintigraphy after radiolabeling of
      sparfloxacin by Tc-99m. Ocular tolerance of the developed nanosuspension was also
      studied by the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method. The
      developed nanosuspension showed a mean particle size in the range of 180 to 190
      nm, suitable for ophthalmic application with zeta potential of -22 mV. In vitro
      release from the developed nanosuspension showed an extended release profile of
      sparfloxacin according to the Peppas model. Acquired gamma camera images showed
      good retention over the entire precorneal area for the developed nanosuspension
      compared with that of a marketed formulation. The marketed drug formulation
      cleared very rapidly from the corneal region and reached the systemic circulation
      through the nasolacrimal drainage system, as significant radioactivity was
      recorded in kidney and bladder after 6 hours of ocular administration, whereas
      the developed nanosuspension cleared at a very slow rate (P < .05) and remained
      at the corneal surface for longer duration, as no radioactivity was observed in
      the systemic circulation. HET-CAM assay with 0 score in 8 hours indicates the
      nonirritant property of the developed nanosuspension. The developed lyophilized
      nanosuspension was found to be stable for a longer duration of time than the
      conventional marketed formulation with a good shelf life. FROM THE CLINICAL
      EDITOR: Poor ocular bioavailability of drugs (<1%) from conventional eye drops is
      mainly due to the eye physiological barriers. In this study, a new colloidal
      system, PLGA nanoparticle for sparfloxacin ophthalmic delivery was demonstrated
      to improve precorneal residence time and ocular penetration. The developed
      lyophilized nanosuspension was found to be stable for longer duration of time
      than conventional marketed formulations.

PMID- 19857607
TI  - Reductive elimination of superoxide: Structure and mechanism of superoxide
      reductases.
AB  - Superoxide anion is among the deleterious reactive oxygen species, towards which
      all organisms have specialized detoxifying enzymes. For quite a long time,
      superoxide elimination was thought to occur through its dismutation, catalyzed by
      Fe, Cu, and Mn or, as more recently discovered, by Ni-containing enzymes.
      However, during the last decade, a novel type of enzyme was established that
      eliminates superoxide through its reduction: the superoxide reductases, which are
      spread among anaerobic and facultative microorganisms, from the three life
      kingdoms. These enzymes share the same unique catalytic site, an iron ion bound
      to four histidines and a cysteine that, in its reduced form, reacts with
      superoxide anion with a diffusion-limited second order rate constant of
      approximately 10(9) M(-1) s(-1). In this review, the properties of these enzymes
      will be thoroughly discussed.

PMID- 19857608
TI  - Effect of phase composition and microstructure of calcium phosphate ceramic
      particles on protein adsorption.
AB  - The biological performance of biomaterials is strongly influenced by their
      protein adsorption characteristics, which are related to the structures and
      properties of both the biomaterial and the protein. In the present study two
      groups of hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramic
      powders were fabricated by different drying processes. The roles of the phase
      composition and microstructure of the powders in the adsorption of various model
      proteins were evaluated. The experimental results showed that BCP always had a
      higher ability to adsorb fibrinogen, insulin or type I collagen (Col-I) than HA.
      The microporosity and micropore size of the CaP particles also had a strong
      impact on their protein adsorption characteristics. HA and BCP particles with
      higher microporosities and/or more micropores >20 nm in diameter could adsorb
      more fibrinogen or insulin. However, amounts of adsorbed Col-I were largely
      unaffected by the microstructure of HA and BCP particles.

PMID- 19857609
TI  - Biological responses of human osteoblasts and osteoclasts to flame-sprayed
      coatings of hydroxyapatite and fluorapatite blends.
AB  - The aim of this study was to determine how the activities of human osteoblastic
      cells and osteoclasts respond to substrates of thermal-sprayed mechanical blends
      of hydroxyapatite and fluorapatite with a view of determining an optimal blend
      ratio for osseointegration. Human osteoblastic cells and osteoclasts were grown
      on titanium alloy discs coated with blends of hydroxyapatite and fluorapatite,
      with concentrations ranging from 0 to 100% fluorapatite. Human osteoblastic cells
      attached in greater numbers and proliferated at a greater rate on blends
      containing 40% fluorapatite. Human osteoblastic cells grown on blends containing
      40% fluorapatite for 7 days also expressed the highest levels of mRNA for several
      proteins involved with regulating bone metabolism (osteoprotegerin and receptor
      activator nuclear factor kappa B ligand), and bone formation (osteopontin,
      osteonectin and bone sialoprotein 1). Osteoclasts resorbed the dentine but poorly
      resorbed the hydroxyapatite-fluorapatite blends, particularly at high levels of
      fluorapatite. This in vitro study demonstrates that thermal-sprayed
      hydroxyapatitecoatings containing 40% fluorapatite may promote optimal bone
      growth and improve osseointegration of implants.

PMID- 19857610
TI  - Postcholecystectomy syndrome (PCS).
AB  - The term postcholecystectomy syndrome (PCS) comprises a heterogeneous group of
      symptoms and findings in patients who have previously undergone cholecystectomy.
      Although rare, these patients may present with abdominal pain, jaundice or
      dyspeptic symptoms. Many of these complaints can be attributed to complications
      including bile duct injury, biliary leak, biliary fistula and retained bile duct
      stones. Late sequelae include recurrent bile duct stones and bile duct
      strictures. With the number of cholecystectomies being performed increasing in
      the laparoscopic era the number of patients presenting with PCS is also likely to
      increase. We briefly explore the syndrome and its main aetiological theories.

PMID- 19857611
TI  - De novo deletion of chromosome 11q13.4-q14.3 in a boy with microcephaly, ptosis
      and developmental delay.
AB  - Many distal deletions of chromosome 11q have been described, but reports on
      deletions of 11q13-q14 are rare in the literature. Here we describe the genotype
      and phenotype of a boy with a deletion of this region. We fine mapped the
      aberration with array-CGH, revealing an 18.2 Mb deletion. The main clinical
      features included microcephaly, ptosis and moderate developmental delay. The
      symptoms partially overlap with previously reported patients with a deletion in
      the same region.

PMID- 19857612
TI  - Proteomics of the response of Arabidopsis thaliana to infection with Alternaria
      brassicicola.
AB  - We have studied the proteome of the model plant Arabidopsis thaliana infected
      with a necrotrophic fungal pathogen, Alternaria brassicicola. The Arabidopsis-A.
      brassicicola host-pathogen pair is being developed as a model genetic system for
      incompatible plant-fungal interactions, in which the spread of disease is limited
      by plant defense responses. After confirming that a defense response was induced
      at the transcriptional level, we identified proteins whose abundance on 2-DE gels
      increased or decreased in infected leaves. At least 11 protein spots showed
      reproducible differences in abundance, increasing or decreasing during the
      progress of the infection. The pathogenesis-related protein PR4, a glycosyl
      hydrolase, and the antifungal protein osmotin are strongly up-regulated. Two
      members of the Arabidopsis glutathione S-transferase (GST) family increased in
      abundance in infected leaves. The spots in which these GST proteins were
      identified contain additional members of the GST family. Representation of GST
      family members in several protein spots migrating at similar molecular weight
      suggests post-translational modifications. The signature of GST regulation may be
      specific for the type of plant-pathogen interaction. The proteomic view of the
      defense response to A. brassicicola can be compared with other types of plant
      pathogen interactions, and to leaf senescence, identifying unique regulatory
      patterns.

PMID- 19857613
TI  - Loading-related regulation of gene expression in bone in the contexts of estrogen
      deficiency, lack of estrogen receptor alpha and disuse.
AB  - Loading-related changes in gene expression in resident cells in the tibia of
      female mice in the contexts of normality (WT), estrogen deficiency (WT-OVX),
      absence of estrogen receptor alpha (ERalpha(-/-)) and disuse due to sciatic
      neurectomy (WT-SN) were established by microarray. Total RNA was extracted from
      loaded and contra-lateral non-loaded tibiae at selected time points after a
      single, short period of dynamic loading sufficient to engender an osteogenic
      response. There were marked changes in the expression of many genes according to
      context as well as in response to loading within those contexts. In WT mice at 3,
      8, 12 and 24 h after loading the expression of 642, 341, 171 and 24 genes,
      respectively, were differentially regulated compared with contra-lateral bones
      which were not loaded. Only a few of the genes differentially regulated by
      loading in the tibiae of WT mice have recognized roles in bone metabolism or have
      been linked previously to osteogenesis (Opn, Sost, Esr1, Tgfb1, Lrp1, Ostn, Timp,
      Mmp, Ctgf, Postn and Irs1, BMP and DLX5). The canonical pathways showing the
      greatest loading-related regulation were those involving pyruvate metabolism,
      mitochondrial dysfunction, calcium-induced apoptosis, glycolysis/gluconeogenesis,
      aryl hydrocarbon receptor and oxidative phosphorylation. In the tibiae from WT
      OVX, ERalpha(-/-) and WT-SN mice, 440, 439 and 987 genes respectively were
      differentially regulated by context alone compared to WT. The early response to
      loading in tibiae of WT-OVX mice involved differential regulation compared to
      their contra-lateral non-loaded pair of fewer genes than in WT, more down
      regulation than up-regulation and a later response. This was shared by WT-SN. In
      tibiae of ERalpha(-/-) mice, the number of genes differentially regulated by
      loading was markedly reduced at all time points. These data indicate that in
      resident bone cells, both basal and loading-related gene expression is
      substantially modified by context. Many of the genes differentially regulated by
      the earliest loading-related response were primarily involved in energy
      metabolism and were not specific to bone.

PMID- 19857614
TI  - Transient muscle paralysis disrupts bone homeostasis by rapid degradation of bone
      morphology.
AB  - We have previously shown that transient paralysis of murine hindlimb muscles
      causes profound degradation of both trabecular and cortical bone in the adjacent
      skeleton within 3 weeks. Morphologically, the acute loss of bone tissue appeared
      to arise primarily due to osteoclastic bone resorption. Given that the loss of
      muscle function in this model is transient, we speculated that the stimulus for
      osteoclastic activation would be rapid and morphologic evidence of bone
      resorption would appear before 21 days. We therefore utilized high-resolution in
      vivo serial micro-CT to assess longitudinal alterations in lower hindlimb muscle
      volume, proximal tibia trabecular, and tibia mid-diaphysis cortical bone
      morphology in 16-week-old female C57 mice following transient calf paralysis from
      a single injection of botulinum toxin A (BtA; 2U/100 g body weight). In an acute
      study, we evaluated muscle and bone alterations at days 0, 3, 5, and 12 following
      transient calf paralysis. In a chronic study, following day 0 imaging, we
      assessed the recovery of these tissues following the maximum observed trabecular
      degradation (day 12) through day 84 post-paralysis. The time course and degree of
      recovery of muscle, trabecular, and cortical bone varied substantially.
      Significant atrophy of lower limb muscle was evident by day 5 of paralysis,
      maximal at day 28 (-34.1+/-0.9%) and partially recovered by day 84. Trabecular
      degradation within the proximal tibia metaphysis occurred more rapidly, with
      significant reduction in BV/TV by day 3, maximal loss at day 12 (-76.8+/-2.9%)
      with only limited recovery by day 84 (-51.7+/-5.1% vs. day 0). Significant
      cortical bone volume degradation at the tibia mid-diaphysis was first identified
      at day 12, was maximal at day 28 (-9.6+/-1.2%), but completely recovered by day
      84. The timing, magnitude, and morphology of the observed bone erosion induced by
      transient muscle paralysis were consistent with a rapid recruitment and prolific
      activation of osteoclastic resorption. In a broader context, understanding how
      brief paralysis of a single muscle group can precipitate such rapid and profound
      bone resorption in an adjacent bone is likely to provide new insight into how
      normal muscle function modulates bone homeostasis.

PMID- 19857615
TI  - Osteo-transcriptomics of human mesenchymal stem cells: accelerated gene
      expression and osteoblast differentiation induced by vitamin D reveals c-MYC as
      an enhancer of BMP2-induced osteogenesis.
AB  - Bone marrow-derived human mesenchymal stem cells (hMSCs) have the in vitro
      capacity to differentiate into osteoblasts, chondrocytes or adipocytes, depending
      on the applied stimulus. In order to identify novel regulators of osteogenesis in
      hMSCs, osteo-transcriptomics was performed whereby differentiation induced by
      dexamethasone (DEX), DEX+ bone morphogenetic protein 2 (BMP2), and DEX+ Vitamin
      D(3) (1,25(OH)(2)D(3)) was studied over a course of 12 days. Microarray analysis
      revealed that 2095 genes were significantly regulated by DEX+ 1,25(OH)(2)D(3), of
      which 961 showed accelerated expression kinetics compared to treatment by DEX
      alone. The majority of these genes were accelerated 24-48 h after onset of
      osteogenic treatment. Gene ontology (GO) analysis of these 1,25(OH)(2)D(3)
      accelerated genes indicated their involvement in biological processes related to
      cellular differentiation and cell cycle regulation. When compared to cells
      treated with DEX or DEX+BMP2, treatment with DEX+ 1,25(OH)(2)D(3) clearly
      accelerated osteoprogenitor commitment and osteoblast maturation, as measured by
      alkaline phosphatase (ALP) activity and calcification of the matrix. Cell cycle
      progression, as observed after initial growth arrest, was not significantly
      accelerated by 1,25(OH)(2)D(3) and was not required for onset and progression of
      osteogenesis. However, expression of c-Myc was accelerated by 1,25(OH)(2)D(3),
      and binding sites for c-MYC were enriched in promoters of genes accelerated by
      1,25(OH)(2)D(3). Lentiviral overexpression of c-MYC strongly promoted DEX+ BMP2
      induced osteoblast differentiation and matrix maturation. In conclusion, our
      studies show for the first time that 1,25(OH)(2)D(3) strongly accelerates
      expression of genes involved in differentiation of hMSCs and, moreover, identify
      c-MYC as a novel regulator of osteogenesis.

PMID- 19857616
TI  - The daily habitual in vivo strain history of a non-weight-bearing bone.
AB  - Daily mechanical loading strongly influences the architecture and composition of
      bone tissue. Throughout the day, the amplitudes, rates, frequencies, and the
      dispersion over time of these loads vary. Nevertheless, most experimental and
      descriptive studies on the aforementioned relationship consider only cyclic
      loading and, in addition, focus on weight-bearing bones. A more complete
      assessment of the daily loading of bone might lead to a better understanding of
      the natural everyday stimulus for bone maintenance or adaptive responses. In the
      present study, we measured the daily habitual strain history of the non-weight
      bearing mandible bone in the rabbit. Long-term continuous strain recordings were
      made using an implantable telemetry device able to read out bone-bonded strain
      gauges. The lateral surface of the rabbit mandibular corpus was chosen as the
      bone surface of interest. During the recordings, which lasted up to 33 h, the
      rabbits (N=7) were able to move unrestrictedly in their cages, performing their
      habitual behaviours. Analysis of the recordings revealed that the measured bone
      surface was subjected to 2.9 (+/-1.4)x10(3) strain events per hour of which 1.8
      (+/-1.0)x10(3) had amplitudes < or =10 microstrains (muvarepsilon). Larger strain
      amplitudes occurred less often and principal strains fell within the range of 
      517 (+/-118) muvarepsilon to 298 (+/-81) muvarepsilon. Strain rates never
      exceeded 10,000 muvarepsilon/s and only 8.9% (+/-7.2%) of the habitual strain
      rates were higher than 1000 muvarepsilon/s. Strain frequency spectra displayed
      clear peaks at 4-5 and 9 Hz. The wirelessly recorded daily strain history of the
      rabbit mandible featured peak strain amplitudes resembling those of other
      mammalian mandibles, but much smaller than those found in many long-bone strain
      measurements.

PMID- 19857617
TI  - Ubiquitous overexpression of Hey1 transcription factor leads to osteopenia and
      chondrocyte hypertrophy in bone.
AB  - The transcription factor Hey1, a known Notch target gene of the HES family, has
      recently been described as a target gene of bone morphogenetic protein-2 (BMP-2)
      during osteoblastic differentiation in vitro. As the role of Hey1 in skeletal
      physiology is unknown, we analyzed bones of mice ubiquitously lacking or
      overexpressing Hey1. This strategy enabled us to evaluate whether Hey1 modulation
      in the whole organism could serve as a drug or antibody target for therapy of
      diseases associated with bone loss. Hey1 deficiency resulted in modest osteopenia
      in vivo and increased number and activity of osteoclasts generated ex vivo. Hey1
      overexpression resulted in distinct progressive osteopenia and inhibition of
      osteoblasts ex vivo, an effect apparently dominant to a mild inhibition of
      osteoclasts. In both Hey1 deficient and overexpressing mice, males were less
      affected than females and skeleton was not affected during development. Bone
      histomorphometry did not reveal major changes in animals at 20 weeks, suggesting
      that modulation had occurred before. Adult Hey1 transgenics also displayed
      increased type X collagen expression and an enlarged hypertrophic zone in the
      growth plate. Taken together, our data suggest that ubiquitous in vivo Hey1
      regulation affects osteoblasts, osteoclasts and chondrocytes. Due to the complex
      role of Hey1 in bone, inhibition of Hey1 does not appear to be a straightforward
      therapeutic strategy to increase the bone mass.

PMID- 19857618
TI  - Three-month weight reduction does not compromise bone strength in obese
      premenopausal women.
AB  - Weight loss is claimed to cause bone loss. This prospective 12-month study
      evaluated effects of 3-month group-based weight loss with VLED on body
      composition, bone mass and strength (DXA and pQCT), muscle performance and
      biomarkers of bone turnover. The assessments were done at baseline and at 3 and
      12 months. Sixty-two women of the recruited 75 obese (BMI>30) premenopausal women
      who completed the study were divided into 3 groups based on the tertiles of
      weight loss at 3 months. The group means of weight losses were 15.5% (Large),
      10.5% (Medium) and 5.9% (Low). Statistical analyses were based on analysis of
      covariance. Bone turnover increased during the weight reduction period in all
      groups but practically returned to baseline during the weight maintenance phase.
      In general, mean bone changes remained marginal (approximately +/-1%) and the
      amount of weight reduction was not associated with bone loss. The only notable
      change was the 4% decline in bending strength at the distal radius. These results
      indicate that in obese premenopausal women, 3-month weight reduction resulted in
      increased bone turnover but was not deleterious for bone mass or strength at 3
      months or after 9-month weight maintenance.

PMID- 19857619
TI  - Bisphosphonates do not inhibit periosteal bone formation in estrogen deficient
      animals and allow enhanced bone modeling in response to mechanical loading.
AB  - The suppressive effects of bisphosphonates (BPs) on bone remodeling are clear yet
      there is conflicting data concerning the effects of BPs on modeling (specifically
      formation modeling on the periosteal surface). The normal periosteal expansion
      that occurs during aging has significant benefits to maintaining/improving the
      bones' mechanical properties and thus it is important to understand whether BPs
      affect this bone surface. Therefore, the purpose of this study was to determine
      the effects of BPs on periosteal bone formation modeling induced by ovariectomy
      (OVX) and mechanical loading. Six-month-old Sprague-Dawley OVX rats (n=60;
      12/group) were administered vehicle, risedronate, alendronate, or zoledronate at
      doses used clinically for treatment of post-menopausal osteoporosis. Three weeks
      after initiating BP treatment, all animals underwent in vivo ulnar loading of the
      right limb every other day for 1 week (3 total sessions). Periosteal surface
      mineral apposition rate, mineralizing surface, and bone formation rate were
      determined at the mid-diaphysis of both loaded (right) and non-loaded (left)
      ulnae. There was no significant effect of any of the BPs on periosteal bone
      formation parameters compared to VEH-treated animals in the non-loaded limb,
      suggesting that BP treatment does not compromise the normal periosteal expansion
      associated with estrogen loss. Mechanical loading significantly increased BFR in
      the loaded limb compared to the non-loaded limb in all BP-treated groups, with no
      difference in the magnitude of this effect among the various BPs. Collectively,
      these data show that BP treatment, at doses comparable to those used for
      treatment of post-menopausal osteoporosis, (1) does not alter the periosteal
      formation activity that occurs in the absence of estrogen and (2) allows normal
      stimulation of periosteal bone formation in response to the anabolic stimulation
      of mechanical loading.

PMID- 19857620
TI  - No wonder less IS more!

PMID- 19857621
TI  - Our window to the world.

PMID- 19857622
TI  - Are food allergies on the rise, or is it misdiagnosis?

PMID- 19857623
TI  - Medical record retention and maintenance for private practices.

PMID- 19857624
TI  - The patient-centered medical home: what is it and why it's important to dietetics
      practitioners.

PMID- 19857625
TI  - Using the energy gap to address obesity: a commentary.

PMID- 19857626
TI  - Health-At-Every-Size and eating behaviors: 1-year follow-up results of a size
      acceptance intervention.
AB  - BACKGROUND: Poor long-term success observed with current weight-control
      strategies stresses the relevance to explore new weight management approaches.
      OBJECTIVE: To assess the effects of a Health-At-Every-Size (HAES) intervention on
      eating behaviors, appetite sensations, metabolic and anthropometric variables,
      and physical activity levels in women at 6-month and 1-year postintervention.
      DESIGN: Randomized controlled trial; measurements at baseline, at the end of the
      intervention period (4 months), and at 6-month and 1-year postintervention (10
      months and 16 months, respectively). Intervention and testing took place from
      September 2003 to August 2006. PARTICIPANTS/SETTING: Premenopausal
      overweight/obese women (n=144; mean age of 42.3+/-5.6 years), recruited from free
      living, general community. INTERVENTION: Women were randomly assigned to: HAES
      group (n=48), social support group (n=48), or control group (n=48). MAIN OUTCOME
      MEASURES: Eating behaviors (restraint, disinhibition, and susceptibility to
      hunger), appetite ratings (desire to eat, hunger, fullness, and prospective food
      consumption), anthropometric and metabolic variables (body mass index, waist and
      hip circumferences, blood lipid levels, and blood pressure), and engagement in
      moderate to intense physical activity (energy cost > or =1.2 k cal x kg(-1) x 15
      minutes(-1) [> or =4.8 metabolic equivalents]). STATISTICAL ANALYSES PERFORMED:
      Changes for each dependent variable were assessed by linear mixed models
      according to a group (HAES vs social support vs control) by time (baseline vs 4
      months vs 10 months vs 16 months) split-plot design. RESULTS: Situational
      susceptibility to disinhibition and susceptibility to hunger significantly
      decreased over time in both HAES group (-0.9+/-0.2 and -1.3+/-0.5, respectively)
      and the social support group (-0.4+/- 0.2 and -1.4+/-0.5, respectively). Although
      eating behavior scores observed at 16 months did not differ between HAES and
      social support groups (situational susceptibility to disinhibition: 2.5+/-0.2 in
      HAES group vs 2.7 +/- 0.2 in social support group; susceptibility to hunger:
      4.2+/-0.5 in both groups), they were lower in these groups than scores noted in
      the control group (3.3+/-0.2 for situational susceptibility to disinhibition and
      5.9+/-0.5 for susceptibility to hunger). CONCLUSIONS: These results suggest that,
      when compared to a control group, an HAES approach could have long-term
      beneficial effects on eating behaviors related to disinhibition and hunger. In
      addition, our study did not show distinctive effects of the HAES approach in
      comparison to a social support intervention.

PMID- 19857627
TI  - Added soluble fiber enhances the satiating power of low-energy-density liquid
      yogurts.
AB  - BACKGROUND: Low-energy-density foods with high satiating power may be useful
      tools for weight management. Energy density of yogurts can range from 0.4 to 1.8
      kcal/g. OBJECTIVE: To test the effects of added inulin, a soluble fiber, on the
      satiating properties of low-energy-density and high-energy-density yogurt
      beverages (16 oz or 472 mL). DESIGN: The study followed a within-subject preload
      design with repeated measures. Each participant completed six conditions,
      presented in a counterbalanced order. SUBJECTS: Participants were 18 men and 20
      women, aged 18 to 35 years. INTERVENTION: The experimental conditions were two
      high-energy-density yogurt beverages (440 kcal; 0.9 kcal/g) and two low-energy
      density yogurt beverages (180 kcal; 0.4 kcal/g) with or without inulin (6 g) and
      an equal volume of orange juice (180 kcal). A no beverage control condition was
      used as well. MAIN OUTCOME MEASURES: Repeated ratings of hunger, fullness, and
      desire to eat and energy consumption at the lunch meal served 120 minutes post
      ingestion were the main measures. STATISTICAL ANALYSES PERFORMED: Repeated
      measures analyses of variance were used to analyze motivational ratings and
      energy and nutrient intakes at the test meal. RESULTS: Yogurt beverages and
      liquid orange juice significantly suppressed appetite and promoted satiety
      relatively to the no beverage condition. Yogurt beverages had greater satiating
      power than did orange juice, as evidenced by higher satiety ratings and reduced
      energy intakes at lunch. The satiating power of low-energy-density yogurt with
      inulin was comparable to that of high-energy-density yogurt. CONCLUSIONS: Energy
      presented in liquid form can have satiating power. Added fiber can potentiate the
      satiating properties of low-energy-density liquid yogurts. Adding fiber to low
      energy-density foods may be an effective way to suppress appetite and control
      food intake.

PMID- 19857628
TI  - Weight control behaviors and dietary intake among adolescents and young adults:
      longitudinal findings from Project EAT.
AB  - BACKGROUND: Cross-sectional research has found that dieting during adolescence
      and the use of extreme weight control behaviors are related to less healthful
      dietary patterns; however, little is known regarding longitudinal relationships.
      OBJECTIVE: To describe patterns of weight control behavior over 5 years and
      examine relationships with nutritional outcomes in adolescents and young adults.
      DESIGN: Population-based, longitudinal study in Minnesota. Youth completed Time 1
      surveys in 1998-1999, and Time 2 surveys were completed in 2003-2004.
      SUBJECTS/SETTING: The Project EAT (Eating Among Teens) survey and the Youth and
      Adolescent Food Frequency Questionnaire were completed by 1,242 females and 1,007
      males in school classrooms at Time 1 and by mail at Time 2. OUTCOME MEASURES AND
      STATISTICAL ANALYSES PERFORMED: Generalized linear modeling was used to predict
      each Time 2 outcome of interest (ie, meal and snack frequencies and dietary
      intake) across patterns of healthful and unhealthful weight control behavior (ie,
      never-engaging, stopping, starting, and persisting). RESULTS: Approximately 45%
      of females and 17% of males reported persistent use of unhealthful weight control
      behaviors at both time points. Persisting to use only healthful weight control
      behaviors was reported by 10% of females and 15% of males. Among females,
      persistent use of unhealthful weight control behavior was associated (P<0.05)
      with measures of poorer dietary intake (eg, lower intakes of calcium and
      vegetables) and less frequent meals, whereas persistent use of healthful weight
      control behavior was associated with measures (P<0.05) of better dietary intake
      (eg, less fast food and fewer sugar-sweetened drinks). Among males, few
      associations were observed between dietary intake and either unhealthful or
      healthful weight control behavior. CONCLUSIONS: Health professionals should guide
      youth who have weight concerns by encouraging healthful eating habits to achieve
      or maintain appropriate weight and nutrition goals.

PMID- 19857629
TI  - Differences in fruit and vegetable intake among Hispanic subgroups in California:
      results from the 2005 California Health Interview Survey.
AB  - OBJECTIVE: To compare total fruit and vegetable intake in cup equivalents and its
      individual components among Hispanic subgroups in California. METHODS: Data are
      from the adult portion of the 2005 California Health Interview Survey.
      Hispanic/Latino subjects (n=7,954) were grouped into six subcategories (Mexican,
      Central American, Caribbean, Spanish American, South American, and >1 group).
      Total fruit and vegetable intake in cup equivalents was estimated from frequency
      responses about seven food categories. Both t test and chi(2) test were used to
      assess differences in sociodemographic characteristics across Hispanic subgroups.
      Multivariate linear regressions using SUDAAN software (Survey Data Analysis,
      version 9.0.1, 2005, Research Triangle Institute, Research Triangle Park, NC)
      were conducted to obtain means of total fruit and vegetable intake in cup
      equivalents and its components by Hispanic subgroups controlling for confounders.
      RESULTS: Hispanic subgroups did not differ in their intake of total fruit and
      vegetable intake in cup equivalents (mean 3.4 c and 2.9 c for men and women,
      respectively). Small but significant differences (P<0.01) were found across
      Hispanic subgroups in individual fruit and vegetable components (green salad
      [women only], cooked dried beans and nonfried white potatoes) after adjusting for
      potential sociodemographic and acculturation confounders. CONCLUSIONS: Fruit and
      vegetable intake by Hispanic respondents did not meet the national
      recommendation, although their reported intake is higher compared to other
      race/ethnicity groups. The public health message remains the same: Increase fruit
      and vegetable intake. Examination of intake for subgroups of Hispanics may
      enhance the utility of dietary information for surveillance, program and message
      design, and intervention and evaluation.

PMID- 19857630
TI  - Weighty concerns: the growing prevalence of obesity among older adults.
AB  - The prevalence of obesity among older adults has increased during the past 20
      years and will affect both medical and social services. Along with an increased
      risk of cardiovascular disease, diabetes, and several cancers, obesity is
      associated with increased risk of physical and cognitive disability. However,
      relatively little attention has been given to the issue of weight management
      among community-dwelling older adults. Intentional weight loss in obese older
      adults has not been widely advocated by health care providers due to the
      uncertainty of whether the benefits outweigh the risks. Limited data in older
      adults show that intentional weight loss is effective in improving diabetes,
      cardiovascular risk factors, and physical function. This review describes the
      changes in body composition associated with aging, the consequences of obesity in
      older adults, and the effect of intentional weight loss on chronic disease risk
      factors and physical function. Recommendations for weight loss in obese older
      adults that minimize the likelihood of adverse effects on muscle mass, bone
      density, or other aspects of nutritional status are reviewed. Specific
      recommendations for macronutrient intake, in particular protein, and selected
      micronutrients, vitamin D and B-12, as well as dietary fiber, and fluid intake as
      part of a hypocaloric diet and recommendations for physical activity are
      described. As part of the health professionals team, dietetics practitioners need
      to be able to guide and manage weight loss treatment options on an individual
      basis by evaluating the potential benefits against the potential risks in obese
      older adults.

PMID- 19857631
TI  - Feasibility of the Young Children's Nutrition Assessment on the Web.
AB  - Methods to assess detailed dietary data are cumbersome, expensive, and difficult
      to implement with large samples. The purpose of the present article was to
      evaluate the feasibility of collecting data from parents about their child's diet
      using an online dietary assessment tool. The Young Children's Nutrition
      Assessment on the Web was developed as part of a longitudinal study of familial
      influences on food intake of preschool children. A sample of 862 parents from 56
      nursery schools completed a paper-and-pencil questionnaire containing
      sociodemographic variables and a food frequency questionnaire about their child's
      diet and psychosocial variables. Subsequently, a subset of parents was asked to
      either complete a paper-and-pencil food diary or the Young Children's Nutrition
      Assessment on the Web (n=88); those remaining who provided e-mail addresses were
      asked to complete the Young Children's Nutrition Assessment on the Web (n=467)
      and a user-acceptability questionnaire. This resulted in 39 useful paper-and
      pencil diaries, 217 useful Young Children's Nutrition Assessments on the Web, and
      164 user-acceptability questionnaires. Mann-Whitney U tests comparing nutrient
      (macronutrients, vitamin C, calcium, and fiber) and food group intakes from data
      collected with the Young Children's Nutrition Assessment on the Web vs paper-and
      pencil diaries resulted in no substantial differences except for water. Attrition
      analyses indicated that dropout for the online assessment was associated with the
      sex of the respondent (father completing the questionnaire), lower social status,
      being a smoker, and lower nutrition knowledge. The online measure was well
      received by respondents. The majority found it user-friendly (79%), attractive
      (68%), and clear (93%). The Young Children's Nutrition Assessment on the Web is a
      promising tool to collect online dietary data in large-scale surveys.

PMID- 19857632
TI  - Unrealistic weight-loss goals among obese patients are associated with age and
      causal attributions.
AB  - Unrealistic weight-loss goals may impede the success of weight-loss attempts. The
      aim of this study was to examine the frequency of unrealistic goals and their
      association with other patient characteristics at the start of a weight-loss
      program. For patients with a body mass index (calculated as kg/m(2)) of 30 to 35,
      35 to 40, or 40 to 50, medically advised weight-loss goals were set at 10%, 15%,
      and 20% of current weight, respectively. Personal weight-loss goals exceeding the
      medically advised goal by >50% were considered unrealistic. Obesity-related
      beliefs were measured by the "Obesity Cognition Questionnaire" and the eating
      behavior self-efficacy scale of the "Obesity Psychosocial State Questionnaire."
      From September 2003 until March 2006, 90 patients were enrolled in the study, 26
      men and 64 women, with a mean age of 43 years (range=18 to 68 years) and body
      mass indexes ranging from 30 to 50. Unrealistic goals were observed in 49% of the
      patients and were more frequent in younger patients (P=0.03), in patients
      attributing their obesity to physical causes (r=0.35, P=0.001), and in patients
      not attributing their obesity to behavioral causes (r=-0.28, P=0.008). This study
      confirms that discrepancies in weight-loss goals between obese patients and
      professionals occur frequently. Because unrealistic goals can hamper long-term
      outcomes of weight-loss programs, better outcomes could possibly be achieved by
      addressing unrealistic weight-loss goals before treatment.

PMID- 19857633
TI  - Nutritional inadequacies in patients with stable heart failure.
AB  - Sodium restriction is the primary nutritional strategy in heart failure; however,
      other diet-related concerns may also occur. We characterized dietary intake among
      stable patients with heart failure and a non-heart-failure cardiac control group
      to quantify and determine prevalence of inadequate micronutrient intake. Two 3
      day food records were completed by 123 patients with heart failure and 58
      controls. A subset of each group provided two 24-hour urine collections. Mean
      intake of sodium (2,540+/-1,122 vs 2,596+/-1,184 mg/day) and potassium (3,190+/
      980 vs 3,114+/-828 mg/day) was similar between the heart failure and control
      groups. Prevalence of inadequate potassium intake was 94% among patients with
      heart failure and 91% among controls. More than 50% in each group had inadequate
      intakes of calcium, magnesium, folate, and vitamins D and E. In stable patients
      with heart failure, sodium intake was not excessive. However, we demonstrated
      widespread dietary inadequacies of other vitamins and minerals. These findings
      highlight the importance of diet beyond that of sodium restriction.

PMID- 19857634
TI  - Recovery to resting metabolic state after walking.
AB  - Metabolic rate is usually measured in a resting state. To achieve this, a period
      of up to 30 minutes is given to recover from walking prior to the test. A work
      group from the American Dietetic Association recommends that 10 to 20 minutes is
      sufficient to achieve rest, but supporting data are limited. The purpose of this
      prospective observational study then was to determine how much time is needed for
      adults to recover to rest after walking 300 meters. Each participant's metabolic
      rate was measured with indirect calorimetry for 30 minutes after a 30-minute
      rest. The participant then walked 300 meters on a measured course, and metabolic
      rate was measured again for 30 minutes. Recovery to rest was considered to have
      occurred when the measured metabolic rate returned to a level of less than 6%
      above the resting measurement. Forty healthy ambulatory adults completed this
      study. Analysis of variance indicated that after a 300-meter walk, resting level
      of metabolic rate was achieved by the 10th minute of rest. However, it took 20
      minutes for 95% of all participants to meet the 6% threshold (the remaining 5%
      who did not reach the threshold were observed to be moving during the
      measurement). The results of this study indicate that if a person lies still,
      recovery to rest after walking occurs by 20 minutes, validating the
      recommendation made by the expert panel of the American Dietetic Association's
      work group on indirect calorimetry. Rest periods of 30 minutes are not required,
      but the person should be observed for movement.

PMID- 19857635
TI  - Psychological effects of prescriptive vs general lifestyle advice for weight loss
      in young women.
AB  - This study aimed to investigate the effects of prescriptive lifestyle advice with
      quantifiable dietary and physical goals compared to general lifestyle advice on
      weight and psychological outcomes in young women with overweight or obesity. A
      total of 203 women (body mass index 33.3+/-0.3, age 28+/-0.3 years) received
      either prescriptive or general lifestyle advice for weight loss over 12 weeks.
      Linear mixed models found that the prescriptive lifestyle advice group had
      significantly greater weight loss (4.2+/-0.4 kg vs 0.6+/-0.2 kg, P<0.001)
      compared to the general lifestyle advice group. However, the prescriptive
      lifestyle advice group also had greater attrition (48% vs 31%, P<0.05) compared
      to the general lifestyle advice group. Linear mixed models found that the
      prescriptive lifestyle advice group had greater improvement in psychological
      distress (-3.0+/-0.04 vs -1.1+/-0.01, P<0.05) and in self-esteem (3.2+/-0.8 vs 
      0.04+/-0.04, P<0.001) compared to the general lifestyle advice group. Changes in
      psychological distress and self-esteem remained significantly different between
      groups after correcting for weight loss. Food cravings decreased significantly
      over time without group differences (P<0.001 for time). Weight locus of control
      remained unchanged in either group (P>0.05). Drop-outs had greater baseline
      psychological distress (15.1+/-0.7 vs 12.5+/-0.4, P<0.01) and higher food
      cravings (2.42+/-0.07 vs 2.24+/-0.05, P=0.049) compared to completers. In
      conclusion, a prescriptive approach is associated with greater weight loss and
      greater improvements in psychological outcomes in young women compared to general
      lifestyle advice. However, these quantitative targets should be accompanied with
      qualitative advice on how they could be met in a variety of circumstances.

PMID- 19857636
TI  - Do food provisions packaged in single-servings reduce energy intake at breakfast
      during a brief behavioral weight-loss intervention?
AB  - Larger portion sizes increase energy intake, yet it is unclear whether single
      serving packages can reduce intake. This study examined the effects of providing
      breakfast foods in single-serving packages and nonportioned packages on energy
      intake of these foods during an 8-week behavioral weight-loss program. In fall
      2005, 19 adults (mean body mass index [calculated as kg/m(2)]=31.8+/-4.0) were
      randomized to conditions that provided foods in single-serving packages (Single
      Serving) or in nonportioned packages (Standard). Overall amounts and types of
      foods provided were consistent across conditions: cereal and peaches (weeks 1, 3,
      5, and 7) and applesauce and cheese (weeks 2, 4, 6, and 8). Participants were
      instructed to eat one serving of each food for breakfast and not to consume the
      provided foods at other times. Mean daily energy intake of the provided foods was
      the primary dependent variable. The Single-Serving group ate less energy from the
      combined pairs of foods provided together as compared to Standard (cereal and
      peaches, 117.0+/-3.2 kcal/day vs 143.5+/-39.3 kcal/day; P<0.05 and applesauce and
      cheese, 174.2+/-13.5 kcal/day vs 199.0+/-29.4 kcal/day; P<0.05). This effect was
      a result of less energy consumed from cereal and applesauce in Single-Serving
      compared to Standard conditions (cereal, 80.2+/-2.9 kcal/day vs 106.3+/-22.9
      kcal/day; P<0.01 and applesauce, 44.5+/-0.6 kcal/day vs 59.3+/-5.0 kcal/day;
      P<0.01), with no differences in energy consumption for peaches and cheese
      (P>0.10). This suggests that single-serving packages may help reduce energy
      intake at breakfast within the context of a behavioral weight-control program.

PMID- 19857637
TI  - What is the acai berry and are there health benefits?

PMID- 19857639
TI  - Sarcoidosis. Introduction.

PMID- 19857640
TI  - Sarcoidosis: epidemiology, etiology, pathogenesis, and genetics.

PMID- 19857641
TI  - Intrathoracic sarcoidosis.

PMID- 19857642
TI  - Sarcoidosis: extrathoracic manifestations.

PMID- 19857643
TI  - Diagnosis of sarcoidosis.

PMID- 19857644
TI  - Treatment of sarcoidosis.

PMID- 19857645
TI  - PilM/N/O/P proteins form an inner membrane complex that affects the stability of
      the Pseudomonas aeruginosa type IV pilus secretin.
AB  - The highly conserved pilM/N/O/P/Q gene cluster is among the core set of genes
      required for cell surface expression of type IV pili and associated twitching
      motility. With the exception of the outer membrane secretin, a multimer of PilQ
      subunits, the specific functions of the products encoded by this gene cluster are
      poorly characterized. Orthologous proteins in the related bacterial type II
      secretion system have been shown to interact to form an inner membrane complex
      required for protein secretion. In this study, we provide evidence that the
      PilM/N/O/P proteins form a functionally equivalent type IVa pilus complex. Using
      Pseudomonas aeruginosa as model organism, we found that all four proteins,
      including the nominally cytoplasmic PilM, colocalized to the inner membrane.
      Stability studies via Western blot analyses revealed that loss of one component
      has a negative impact on the levels of other members of the putative complex.
      Furthermore, complementation studies revealed that the stoichiometry of the
      components is important for the correct formation of a stable complex in vivo. We
      provide evidence that an intact inner membrane complex is required for optimal
      formation of the outer membrane complex of the type IVa pilus system in P.
      aeruginosa, as PilQ stability is negatively affected in its absence. Finally, we
      show that, in the absence of the pilin subunit, the levels of membrane-bound
      components of the inner membrane complex are negatively regulated by the PilR/S
      two-component system, suggesting a role for PilR/S in sensing the piliation
      status of the cell.

PMID- 19857646
TI  - Periplasmic domains of Pseudomonas aeruginosa PilN and PilO form a stable
      heterodimeric complex.
AB  - Type IV pili (T4P) are bacterial virulence factors responsible for attachment to
      surfaces and for twitching motility, a motion that involves a succession of pilus
      extension and retraction cycles. In the opportunistic pathogen Pseudomonas
      aeruginosa, the PilM/N/O/P proteins are essential for T4P biogenesis, and genetic
      and biochemical analyses strongly suggest that they form an inner-membrane
      complex. Here, we show through co-expression and biochemical analysis that the
      periplasmic domains of PilN and PilO interact to form a heterodimer. The
      structure of residues 69-201 of the periplasmic domain of PilO was determined to
      2.2 A resolution and reveals the presence of a homodimer in the asymmetric unit.
      Each monomer consists of two N-terminal coiled coils and a C-terminal ferredoxin
      like domain. This structure was used to generate homology models of PilN and the
      PilN/O heterodimer. Our structural analysis suggests that in vivo PilN/O
      heterodimerization would require changes in the orientation of the first N
      terminal coiled coil, which leads to two alternative models for the role of the
      transmembrane domains in the PilN/O interaction. Analysis of PilN/O orthologues
      in the type II secretion system EpsL/M revealed significant similarities in their
      secondary structures and the tertiary structures of PilO and EpsM, although the
      way these proteins interact to form inner-membrane complexes appears to be
      different in T4P and type II secretion. Our analysis suggests that PilN interacts
      directly, via its N-terminal tail, with the cytoplasmic protein PilM. This work
      shows a direct interaction between the periplasmic domains of PilN and PilO, with
      PilO playing a key role in the proper folding of PilN. Our results suggest that
      PilN/O heterodimers form the foundation of the inner-membrane PilM/N/O/P complex,
      which is critical for the assembly of a functional T4P complex.

PMID- 19857647
TI  - Presidential address at the 9th congress of the Polish Transplantation Society,
      Krakow, May 16th, 2009.

PMID- 19857648
TI  - Present data on organ donation and transplantation in Poland.
AB  - At present, organ transplantation activity in Poland is located in the middle
      among European Union countries. There are appropriate law regulations, well
      organized legal structures, well-educated transplant teams, good transplantation
      results, and case registries. There are 24 organ transplant teams in 20 centers,
      including 46 programs. Since 1966, over 18,000 organs have been transplanted
      14,300 kidneys; 1800 livers; 1700 hearts; 250 kidney/pancreases and 30 lungs.
      Every year almost 1500 organs are procured from about 500 cadaveric heart-beating
      donors (9-14 per million people [pmp]) with 50 from living donors: 800 to 1000
      kidneys (21-28 pmp); over 200 livers (5-6 pmp); and 60 to 100 hearts (1.6-2.7
      pmp). National transplant registries are maintained in Poltransplant including a
      central registry of refusals (the policy of presumed consent with registered
      objection on donation after death is implemented), waiting lists, a cadaveric and
      living donor registry, and a transplant registry. There are still some actions
      that should be undertaken to strengthen the transplantation system in Poland, to
      increase organ availability, to enhance the efficiency and accessibility of
      transplantation systems, and to improve quality and safety: namely, increasing
      deceased donations to their full potential, appointing transplant coordinators in
      every hospital where there is the potential for organ donation, promoting quality
      improvement programs, and promoting living donation.

PMID- 19857649
TI  - Reversal to whole-brain death criteria after 15-year experience with brain stem
      death criteria in Poland.
AB  - Polish brain-death criteria, similar to the original Harvard criteria, were
      published in 1984. In 1990, they were converted to brainstem death criteria, and
      were revised twice, in 1994 and in 1996. However, they could not be used in many
      complicated clinical situations such as intoxication, metabolic alterations,
      major facial injury, infratentorial lesions, and cervical spinal cord injury. The
      new Polish Transplant Act, passed by the Polish Parliament in 2005, recommends
      implementation of criteria for whole-brain death for brain-death diagnosis. In
      2007, the Polish Ministry of Health Commission outlined new Polish brain-death
      criteria. Optional use of instrumental confirmatory tests was implemented in the
      new Polish national code of practice for the diagnosis of brain death in adults.
      In children up to age 2 years, instrumental tests are obligatory. Initially,
      there were problems in understanding the new, slightly more complicated
      classifications of primary and secondary brain injuries, infratentorial and
      supratentorial processes, modified apnea test. A broad commentary that addressed
      the most frequently asked questions was published in Anesthesiology and Intensive
      Therapy, the official journal of the Polish Society of Anaesthesiology and
      Intensive Therapy. This article dealt with most of the problems associated with
      implementation of the new criteria for diagnosis of brain death.

PMID- 19857650
TI  - Educational system for transplant coordinators in Poland: postgraduate studies at
      Warsaw Medical University; 2 years of experience.
AB  - Donor hospital transplant coordinators play crucial roles in the donation
      process. There are only a few coordinators in Poland, while there are about 400
      hospitals with intensive care units (ICU). Coordinators must be professionals in
      medical sciences, clinical psychology, law, organization, management, and
      statistics. Coordinators acquire these skills during the Transplant Coordinators
      Postgraduate Studies at Warsaw Medical University which began in 2007. Lectures,
      seminars and exercises (99 hours, 6 weekends) are run by experts. The studies end
      with an examination and a diploma. The main criterion for acceptance of a
      candidate is employment in a key department in the donation process. The aim of
      studies is to educate coordinators for each hospital in the country. Until now 4
      editions of the course have been completed. Among 123 graduates, 71 (60%) are
      employed in strategic departments of 48 hospitals. Preliminary results of
      graduates' activities in donor detection were compared in the periods before
      (2005-2006) and after the course (2007-2008). The background was the overall
      activity in Poland, where in 2007-2008 the activity fell to 79% of 2005-2006.
      This fall for hospitals with the graduates of this program was 82% versus
      hospitals without them (76%). Of the 48 hospitals that employed the graduates: 14
      improved donation 5 were the same, in 12 in both periods showed no donations;
      whereas in 11 it was much lower (>20%), and in 6 lower but consistent with the
      national trend.

PMID- 19857651
TI  - Assessment of kidneys procured from expanded criteria donors before
      transplantation.
AB  - BACKGROUND: Using expanded criteria donor (ECD) organs is 1 strategy to make more
      organs available for transplant. To reduce the number of posttransplant
      complications and failures, there is a need to create a comprehensive system of
      evaluation before transplantation, especially for kidneys harvested from ECD. The
      aim of this study was to assess the results of kidneys procured from ECD seeking
      to discover the most useful factors for kidney evaluation before transplantation.
      PATIENTS AND METHODS: One hundred seventy-two patients received cadaveric renal
      transplants between January 1, 2006, and August 31, 2008. We collected data on
      donors, recipients, and perfusion parameters. We analyzed patient and graft
      survivals, as well as immediate, delayed, and slow graft function. Kidney
      recipient function was assessed by serum creatinine concentrations and by
      creatinine clearance calculated according to the Cockroft-Gault formula. Renal
      biopsy specimens were obtained in the perioperative periods 147 cases. RESULTS:
      The overall 1-year graft survival was 86.9%. More than 25% of transplanted
      kidneys were harvested from ECD. There were no significant differences in patient
      survival between recipients of standard criteria donor kidneys (RSCDK) versus of
      expanded criteria donor kidneys (RECDK). One-year graft survival was higher among
      the RSCDK group than the RECDK group, namely, 94.4% versus 62.5%, (P = .004).
      There were no differences in the incidence of primary nonfunction or in delayed
      graft function between the groups. RECDK were more likely to show slow graft
      function (69.2% vs 37.8%; P = .033). A lower graft survival at 6 months after
      transplantation was observed among organs harvested from ECD compared with
      standard criteria donor (SCD) kidneys who showed histologic lesions or a flow at
      the fourth hour of machine perfusion below 0.4 mL/g. Using a logistic regression
      model, chronic histologic changes were shown to influence kidney survival at 6
      months after transplantation. CONCLUSION: There was no significant difference in
      patient survival between recipients of kidneys harvested from expanded versus
      standard criteria donors. ECD kidneys displayed lower graft survival rates. There
      was no significant difference in the incidence of delayed graft function between
      recipients of kidneys harvested from expanded versus standard criteria donors.
      Pretransplant evaluation of ECD kidneys should include 3 variables: donor
      parameters, histologic findings, and machine perfusion parameters.

PMID- 19857652
TI  - Complications of transplantation of kidneys from expanded-criteria donors.
AB  - BACKGROUND: Organ shortage is the primary barrier to kidney transplantation. To
      maximize organ use, organs from expanded-criteria donors (ECDs) have been used
      increasingly. Expanded-criteria donors are defined as individuals older than 60
      years or older than 50 years with at least 2 of the following risk factors:
      hypertension, stroke as the cause of death, or serum creatinine concentration
      greater than 1.5 mg/dL. OBJECTIVE: To assess the incidence of complications
      posttransplantation in ECD kidneys compared with kidneys from standard-criteria
      cadaveric donors (SCDs). PATIENTS AND METHODS: One hundred seventy-two patients
      received cadaveric renal transplants between January 1, 2006, and August 31,
      2008. Donor and recipient data were collected, as well as patient and graft
      survival and immediate, delayed, or slow graft function. Complication rates for
      lymphocele, urinary leak, thrombosis, hematoma, urinary tract infection, and
      cytomegalovirus infection were recorded. Follow-up was for 3 to 35 months, ending
      on November 30, 2008. RESULTS: Overall, mean 1-year graft survival was 86.9%, and
      mean creatinine concentration was 1.58 mg/dL. One incidence of primary
      nonfunction (0.6%) was observed. More than 25% of transplanted kidneys were from
      ECDs. No significant differences were noted in postoperative complications
      between recipients of ECD or SCD organs. CONCLUSION: The rate of complications in
      recipients of ECD and SCD kidneys is comparable.

PMID- 19857653
TI  - Cause of death in multiorgan donors and its relation to the function of
      transplanted kidneys.
AB  - BACKGROUND: Brain death is an important variable contributing to donor-specific
      kidney damage. Poor kidney performance posttransplantation may be related to the
      cause of death of the donor. OBJECTIVE: To assess the influence of cause of death
      in multiorgan donors on the function of transplanted kidneys. MATERIAL AND
      METHODS: Standard criteria for the brain stem death protocol were applied in 146
      potential heart donors included in the study. Conventional supportive management
      consisted of mechanical ventilation to achieve normocapnia, rewarming, and fluid
      and electrolyte replacement. Dopamine infusion not exceeding 10 microg/kg/min and
      desaminovasopressin were titrated to predetermined mean arterial pressure (MAP).
      In renal allograft recipients (n = 232), kidney function was monitored using
      serial serum creatinine concentrations on days 1, 2, 3, 7, 14, 30, and 90
      posttransplantation. The relation between donor cause of death (injury, bleeding,
      or other cause) and recipient serum creatinine concentration was analyzed in the
      postoperative period. RESULTS: Significantly greater serum creatinine
      concentrations were observed up to 14 days posttransplantation in recipients of a
      kidney from a donor who died of any cause other than injury. Recipients of a
      kidney from a donor who died of bleeding exhibited significantly greater serum
      creatinine concentrations at 30 days posttransplantation. CONCLUSIONS: A cause of
      death other than injury or bleeding in a multiorgan donor is predictive of worse
      kidney graft function in the first 14 days posttransplantation. Intracranial
      bleeding in a multiorgan donor is predictive of worse kidney graft function in
      the early period posttransplantation.

PMID- 19857654
TI  - Arteriolar hyalinization in implantation kidney biopsies as a predictor of graft
      function.
AB  - The shortage of organs suitable for transplantation has caused a constant
      evolution of donor acceptance criteria, making an implantation biopsy a valuable
      tool to predict kidney allograft survival. Preimplantation vascular changes may
      be divided into sclerosis or intimal fibrous thickening or arteriolar
      hyalinization. Increasing evidence has indicated their impact on graft function.
      The aim of this study was to evaluate the significance of preimplantation
      arteriolar hyalinization for the stability of kidney allograft function. Among a
      prospective cohort study of 53 kidney recipients (implantation: 2006-2007) who
      showed serum creatinine values between 1 and 2 mg/dL at 3 months after
      engraftment, the mean observation time was 24 +/- 8.7 months. At the end of the
      observation, kidney function as defined by the estimated glomerular filtration
      rate by the Cockcroft-Gault formula (eGFR C-G) was significantly diminished in
      individuals with preimplantation evidences of arteriolar hyalinization (mean
      values: 51.2 +/- 14.8 and 62.0 +/- 16.7, respectively; P < .03) or serum
      creatinine concentrations (1.76 +/- 0.36 vs 1.51 +/- 0.48 mg/dL; P < .09). The
      negative influence of arteriolar hyalinosis on allograft function was time
      dependent; an early satisfactory filtration rate did not preclude progressive
      kidney dysfunction.

PMID- 19857655
TI  - Impact of donor-dependent genetic factors on long-term renal graft function.
AB  - Our aim was to study the association of donor genetic features with long-term
      graft function as well as the impact of donor age, gender compatibility, cold
      ischemia time (CIT), and delayed graft function (DGF). We observed the outcomes
      of 125 kidney recipients for a minimum of 12 months (mean, 30.9 +/- 13.0 months).
      Grafts were obtained from 89 donors who underwent profiling for AHSG 1/2, MMP9 
      1562C/T, IL6 -174G/C, IL1beta 3954C/T, MTHFR 677C/T, MTHFR 1298A/C, NOS3 -786C/T,
      and PAI1 4G/5G single-nucleotide polymorphisms (SNPs) using sequence-specific
      probe (SSP) polymerase chain reaction (PCR) and MPO -463G/A and CRP -390C/T/A
      with restriction fragment length polymorphism (RFLP) analysis. NOS3 IVa/b VNTR
      polymorphism was genotyped by gel electrophoresis of the respective PCR-generated
      DNA fragment. The presence of the aa eNOS genotype was connected with worse graft
      function. The aa genotype was also linked to acute rejection episodes. The lowest
      values of glomerular filtration rate (GFR) were displayed by recipients of grafts
      from donors with homozygotic PAI1 gene 5G polymorphism, linking paradoxically
      with lower PAI-1 synthesis suggesting that the intensity of proteolysis led to
      increased alloantigen specificity stimulating alloresponses. Graft function
      depended significantly on donor age with an influence of gender matching. GFR
      showed a significant dependence on DGF. Genetic features of the donor influenced
      long-term graft function. Variant eNOS gene polymorphism, which produced
      decreased eNOS activity, was linked to worse remote graft function. A similar
      negative impact was observed in the case of donor PAI1 polymorphism, with the
      functional consequence of lower gene product synthesis.

PMID- 19857656
TI  - Liver regeneration in 120 consecutive living-related liver donors.
AB  - BACKGROUND: Living-related liver transplantation for pediatric patients has
      become an acceptable, low-risk treatment option. The aim of this study was to
      assess the extent of donor liver regeneration. MATERIALS AND METHODS: Between
      October 1999 and January 2008, 120 living-related donors provided 109 grafts
      consisting of segments II and III and 11 grafts consisting of segments II, III,
      and IV. Volumetric assessment of the donor liver and selected segments was
      performed using computed tomography. After procurement every graft was weighed.
      At 7 and 30 days, as well as 12 months after the operation the donor liver
      remnant was evaluated for differences in volume. RESULTS: A significant
      correlation was observed between the liver graft mass and its volume as assessed
      by computed tomography (r = 0.781; P < .05). Twelve months after procurement, the
      average regeneration index was significantly higher among donors of segments II,
      III, and IV (144 +/- 23%) versus donors of segments II and III (114 +/- 15%; P <
      .05). CONCLUSION: Liver regeneration after procurement of selected liver segments
      from living donors is a consistent finding. Computed tomography is an accurate
      imaging modality to track changes in liver volume. This study showed a positive
      correlation between the size of the liver graft and the regeneration of the liver
      remnant in the donor.

PMID- 19857657
TI  - Microvesicular liver graft steatosis as a risk factor of initial poor function in
      relation to suboptimal donor parameters.
AB  - OBJECTIVE: We sought to examine the role of microvesicular graft steatosis in
      relation to donor parameters. MATERIALS AND METHODS: We performed 269 consecutive
      orthotopic liver transplantations (OLT) between 2004 and 2006. Donor parameters
      of age, body mass index (BMI), intensive care unit (ICU) stay, hypotension,
      cardiac arrest, pressors, sodium concentration, aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), bilirubin,
      and activated partial thromboplastin time (APTT), as well as the degree of
      microvesicular graft steatosis were collected into the study. The endpoint of the
      study was liver graft dysfunction (AST or ALT > 2500 IU/L or prothrombin index <
      50% during the first 7 days after OLT). RESULTS: The risk of initial poor
      function (IPF) at day 7 posttransplantation was significantly related to hepatic
      microvesicular steatosis (odds ratio [OR] = 1.38 per 1 SD = 9.3%; P < .021).
      Accounting for the influence of the other donor factors produced little change in
      the numerical values of relative risk: from 1.22 (following exclusion of GGT) to
      1.46 (after elimination of the influence of bilirubin concentration). A 50%
      increased risk of IPF was equivalent to 12% of the extent of steatosis.
      CONCLUSION: Microvesicular steatosis is a risk factor for early hepatic
      dysfunction after OLT.

PMID- 19857658
TI  - Intestine as source of cytokines and growth factors.
AB  - BACKGROUND: The activation status of intestinal immune system cells is much
      higher than that of analogous peripheral cells. Increased serum concentrations of
      proinflammatory cytokines have been reported in various pathologic conditions;
      however, the source of these mediators has not been elucidated. OBJECTIVE: To
      assess the role of the human intestine and its lymphatic system in production of
      growth factors and proinflammatory cytokines. MATERIAL AND METHODS: Twenty liver
      transplant recipients and 20 donors were included in the study. Blood samples
      were obtained from the artery supplying the intestine, the portal vein, and a
      peripheral vein during liver harvesting in donors and after transplantation in
      recipients. An enzyme-linked immunosorbent assay was used to assess serum
      concentrations of IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming
      growth factor-beta (TGF-beta), and hepatocyte growth factor (HGF). RESULTS: In
      transplant recipients, IL-6 concentration in arterial blood was lower than that
      in portal blood (P < .049), whereas in donors, there was no significant
      difference in these concentrations. Neither recipients nor donors demonstrated
      significant differences in arterial or portal blood concentrations of TNF-alpha,
      TGF-beta, or HGF. CONCLUSIONS: In healthy human beings, the intestine is not a
      substantial source of IL-6, TNF-alpha, TGF-beta, or HGF. However, in patients
      with liver cirrhosis, the intestine is an important source of IL-6 but not of the
      other studied growth factors and cytokines.

PMID- 19857659
TI  - Pentoxifylline augments fasting-induced nephroprotection in acute ischemic kidney
      injury in rats.
AB  - BACKGROUND: Prolonged fasting exerts anti-inflammatory effects, and
      pentoxifylline (PTX) has similar immunomodulating properties. OBJECTIVE: To
      compare the influence of feeding status and PTX administration on the course of
      acute ischemic kidney injury. MATERIAL AND METHODS: Seven days after right-sided
      nephrectomy and 7 days before renal ischemia, 44 male Sprague-Dawley rats were
      placed in individual cages with unlimited access to water. Rats were divided into
      4 groups; groups Ia and Ib were fed with no limitations, and groups IIa and IIb
      were fasted for 32 hours before renal ischemia. Ninety minutes before clamping of
      the left kidney vascular pedicle, rats in groups Ib and IIb and those in groups
      Ia and IIa, respectively, were given either PTX subcutaneously, 100 mg per
      kilogram of body weight in 1 mL of 0.9% sodium chloride, or 0.9% sodium chloride
      only. Biochemical parameters of renal function were estimated at 48 hours after
      the ischemic event. RESULTS: Both fasting and PTX administration diminished the
      degree of ischemia-induced impairment of renal function. The combined effects
      were additive. CONCLUSIONS: Fasting and treatment with PTX during the preischemic
      period exerts additive nephroprotective effects in the setting of acute ischemic
      kidney injury. This finding may be useful in future practices of preservation and
      kidney transplantation.

PMID- 19857660
TI  - Use of high-dose human immune globulin in highly sensitized patients on the
      kidney transplant waiting list: one center's experience.
AB  - INTRODUCTION: Transplant rates are low among highly sensitized patients with
      preformed anti-HLA antibodies, because of the additional immunologic barrier, the
      increased risk of rejection, and the greater chance of early graft loss.
      Intravenous infusion of pooled human immune globulin (IVIG) is immunomodulatory,
      neutralizing circulating antibodies and reducing rejection rates, two factors
      that may improve long-term transplantation outcomes. METHODS: We selected for
      high-dose IVIG treatment (1 g/kg monthly for 4 months) 10 adult, stage V, highly
      HLA-sensitized (PRA, historical >80% and current 56%-100%) chronic kidney disease
      patients listed for kidney transplantation with a mean waiting time of 7.5 years.
      They spanned age of 29-52 years. Anti-HLA titers were monitored monthly before
      each treatment and 1 month after the last IVIG dose; afterwards, patients were
      placed on an urgent list and followed for their transplant renal function and
      rejection episodes. RESULTS: Although 1 subject was transplanted after the first
      dose of IVIG, 9 patients completed the study, but their PRA decreased only
      insubstantially, namely, 14.4% (range, 8%-28%). During 6-12 months follow-up, 6
      patients were considered for transplantation (negative crossmatch); 5 received
      kidneys and 1 was disqualified due to infection. The recipients were treated with
      antithymocyte globulin (n = 3) or basiliximab (n = 2) as well as
      tacrolimus/mycophenolate/steroids for baseline immunosuppression. Protocol
      biopsies (months 1, 3, and 6) in 4 patients (1 denied consent) revealed
      subclinical acute rejection and C4d positivity in most cases, either repeatedly
      or in the final biopsy. However at 6-12 months the mean serum creatinine
      concentration averaged 1.5 +/- 0.4 mg/dL. CONCLUSION: High-dose human IVIG
      reduced PRA poorly, but short-term transplantation outcomes were encouraging.
      Surveillance biopsies are advised for sensitized kidney recipients due to the
      frequent appearance of rejection, particularly of the antibody mediated type.

PMID- 19857661
TI  - 1,25-dihydroxyvitamin D deficiency predicts poorer outcome after renal
      transplantation.
AB  - OBJECTIVE: To assess 1,25-dihydroxyvitamin D status and the effect of vitamin
      concentration on transplantation outcome in renal allograft recipients. PATIENTS
      AND METHODS: Ninety patients underwent renal transplantation between 2002 and
      2005. All received alfacalcidol supplementation before surgery. 1,25
      Dihydroxyvitamin D concentration was determined on day 3 posttransplantation and
      at 1-, 6-, 12-, 18-, and 24-month follow-up. RESULTS: Severe 1,25
      dihydroxyvitamin D deficiency was noted in 83% of patients immediately
      posttransplantation. From 1 to 12 months thereafter, concentrations increased
      almost 3-fold, and remained constant to 24 months. In 50% of patients, the 1,25
      dihydroxyvitamin D concentration reached a concentration of more than 30 pg/mL,
      similar to that in healthy volunteers; in the other 50%, the concentration
      reached 17.2 pg/mL. A high incidence of delayed graft function was observed in
      patients with 1,25-dihydroxyvitamin D deficiency (44% vs 6%). There was a
      negative correlation between the initial 1,25-dihydroxyvitamin D and serum
      creatinine concentrations at day 3 and month 6 (P < .03). Similarly, the 1,25
      dihydroxyvitamin D concentration at 1 month was negatively correlated with
      creatinine concentration at months 1 through 24 (P < .01). Poor outcome was
      observed primarily in patients with 1,25-dihydroxyvitamin D deficiency; 2
      patients developed cancer, 5 grafts were lost, and 4 patients died of
      cardiovascular events. CONCLUSIONS: 1,25-Dihydroxyvitamin D deficiency is highly
      prevalent in renal allograft recipients. Patients with 1,25-dihydroxyvitamin D
      deficiency are at greater risk of delayed graft function, and the graft is more
      likely to be lost. These findings suggest the necessity of adequate vitamin D
      supplementation both before and after transplantation.

PMID- 19857662
TI  - Pretransplantation cellular alloreactivity is predictive of acute graft rejection
      and 1-year graft function in kidney transplant recipients.
AB  - OBJECTIVE: To study cellular alloimmunity in kidney allograft recipients using an
      interferon-gamma enzyme-linked immunosorbent spot assay (ELISPOT). MATERIAL AND
      METHODS: Donor splenocyte peripheral blood mononuclear cells were obtained during
      kidney recovery in 53 kidney recipients including 11 with positive panel-reactive
      antibodies pretransplantation. For ELISPOT data analysis, the spot number, size,
      and intensity were calculated, reflecting the volume of cytokine secretion at the
      single-cell level. Results were recalculated as the ratio of the values observed
      for donor-stimulated to unstimulated recipient cells corrected for residual donor
      activity. RESULTS: Significantly greater pretransplantation donor-stimulated
      activity was observed in recipients who experienced an acute rejection episode
      (ARE) within 1 year (P < .05). Mean change in spot number, size, and intensity in
      patients without or with AREs was 0.99 vs 3.33, 1.60 vs 6.05, and 1.40 vs 6.31,
      respectively. The assessed parameters were prognostic of high risk of ARE: 1.5
      fold increase in spot number (ARE incidence, 52% vs 9%), 2.5-fold increase in
      spot size (ARE incidence, 53% vs 13%), and 2.7-fold increase in spot intensity
      (ARE incidence, 52% vs 9%). The 3 parameters correlated with 1-year serum
      creatinine concentration (P < .05). In 14 recipients, AREs could have been
      predicted in 11 using pretransplantation ELISPOT results, and in only 2 on the
      basis of panel-reactive antibodies. CONCLUSION: The ELISPOT-determined capacity
      of donor-induced reactivity observed in recipient cells obtained just before
      transplantation is predictive of risk of graft rejection and 1-year allograft
      function.

PMID- 19857663
TI  - Multidrug resistance-associated protein 2 gene (ABCC2) variant in kidney
      allograft recipients.
AB  - Multidrug resistance-associated proteins may play crucial roles in the protection
      of internal organs, particularly the kidneys and liver, from various toxic
      agents. Little is known about their significance in transplanted organ function
      and survival. The aim of the present study was to evaluate the frequency of
      functional ABCC2 4544A>G polymorphism in 165 renal transplant recipients. DNA was
      isolated from peripheral blood and ABCC2 4544A>G polymorphism was assessed by the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. Analysis of allele and genotype frequencies revealed that the presence of
      ABCC2 4544 A allele was associated with prolonged observation time and may have
      an impact on a greater frequency of proteinuria. This observation strongly
      suggested that particular alleles of the ABCC2 gene may contribute to
      transplantation outcomes.

PMID- 19857664
TI  - Current approaches to the use of sirolimus in renal transplantation.
AB  - Sirolimus, a macrolide with immunosuppressive properties, was introduced into
      clinical practice a decade ago. The optimal use of this drug remains
      controversial: It displays a wide range of organ and tissue toxicities owing to
      the critical role of its therapeutic site- the kinase mammalian target of
      rapamycin-in the signal transduction pathways of numerous cytokines, growth
      factors, hormones, and nutrients. However, it displays unique, recognized
      benefits for renal transplant recipients: synergistic interactions with
      cyclosporine and possibly tacrolimus, allowing marked reduction in exposure to
      the calcineurin inhibitor; reduction in the frequency of posttransplant
      malignancies, particularly lymphomas, Kaposi sarcomas, and hypernephromas; and
      modest nephrotoxicity in comparison with calcineurin inhibitors. Because of its
      inhibitory effects on endothelial and smooth muscle cell proliferation, sirolimus
      may be a useful tool to dampen chronic vasculo-obliterative processes that
      attenuate graft survival. With increasing experience with the drug, the true
      potential of sirolimus will be realized to be a critical element in the
      immunosuppressive matrix.

PMID- 19857665
TI  - Safety and tolerance of sodium mycophenolate in patients after renal
      transplantation--an observational study.
AB  - BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS) was developed as an
      alternative agent to mycophenolate mofetil (MMF), aimed at reduction of
      gastrointestinal (GI) complications. METHODS: Seventy-four patients (mean age
      42.3 years) switched from MMF to MPS were included in the study and followed-up
      for 3 months (Visit 0, Visit 2 after 1 month and Visit 3 after 3 months). The
      mean time from transplantation to switch was 3.7 years. During Visit 2 and 3 the
      following were recorded: impact of treatment change on the severity of GI
      symptoms (4 point scale: 1-worsening, 2-no change, 3-improvement, 4-resolution),
      EC-MPS tolerance, adverse events (AEs), patient compliance and physician
      satisfaction with treatment (4 point scale: 1-bad, 2-fair, 3-good, 4-very good).
      RESULTS: Sixty-three patients completed the study (85.1%). EC-MPS dose ranged
      from 720 to 1440 mg. GI symptom severity score averaged at 3.41. Symptoms most
      commonly compelling a conversion were: abdominal pain, diarrhea, abdominal colic,
      nausea, anorexia and vomiting. Out of 175 complaints, 144 (82%) either improved
      or resolved, 5 (2.86%) aggravated, and 25 (14.86%) persisted. Patient compliance
      and mean physician satisfaction score averaged at 3.70 and 3.02 at Visit 3,
      respectively. 9 AEs (2 severe) were reported. Causal relationship with the
      medication was suspected in 5 cases (1 case of SAE). The most common AEs were:
      anemia, infection (including sepsis), GI symptoms (abdominal pain, diarrhea).
      CONCLUSIONS: The following was concluded in our study: (1) sodium mycophenolate
      is well tolerated; (2) after switching from MMF to EC-MPS, gastrointestinal
      symptoms alleviated; (3) EC-MPS is a safe medication, with a low adverse events
      rate.

PMID- 19857667
TI  - Renal parenchyma perfusion spectrum and resistive index (RI) in ultrasound
      examinations with contrast medium in the early period after kidney
      transplantation.
AB  - The main diagnostic method for renal graft dysfunction is color Doppler
      ultrasound with the use of spectrae evaluation of blood flow within the main and
      intrarenal arteries. Ultrasound with contrast medium (US-CM) enhances the
      possibilities of this tool. The aim of this study was to evaluate the efficacy of
      US-CM to assess renal graft perfusion among 18 kidney allograft recipients at 5
      to 10 days after transplantation. Patients underwent pulse inversion sonography
      of the graft during intravenous injections of 2.4 mL SonoVue (Bracco-Altana,
      Italy). Images were quantitatively assessed using computer software to compare
      the time to peak contrast enhancement effect in the renal cortex and renal
      pyramids. The results were compared to Doppler ultrasonography of the renal
      arteries and estimated glomerular filtration rate (eGFR; Modification of Diet in
      Renal Disease [MDRD]). A correlation was observed between eGFR and blood flow
      parameters within the renal arteries, as well between the flow time of contrast
      medium from the artery within the renal hilus to the renal cortex. Increased eGFR
      correlated with subsequent improvement in graft function (r = -.806; P = .001),
      and resistive index (RI) of the renal artery was inversely related to subsequent
      delayed graft function (r = .544; P = .029). Negative correlations were observed
      between eGFR and renal artery RI, as well as between eGFR and time from renal
      artery contrast to maximal contrast enhancement of the renal pyramids. A negative
      correlation was found as well between eGFR and time difference of contrast
      enhancement of the cortex and pyramids. In conclusion, US-CM enhanced the
      efficacy of ultrasound diagnostics of the renal graft and may be used as a
      predictor of graft function in the early posttransplantation period.

PMID- 19857666
TI  - Optimal mycophenolic acid and mycophenolic acid glucuronide levels at the early
      period after kidney transplantation are the key contributors to improving long
      term outcomes.
AB  - INTRODUCTION: Suboptimal mycophenolic acid (MPA) and its metabolite MPA
      glucuronide (MPAG) levels are associated with significant increased incidences of
      graft loss. This study assessed the influence of MPA and MPAG C(0) levels on
      glomerular filtration rate (GFR) values and histopathologic changes in protocol
      biopsies of kidney allograft recipients. PATIENTS AND METHODS: This prospective
      study of 42 low-risk patients receiving mycophenolate mofetil, prednisone, and a
      low or normal cyclosporine dose included histological assessment, according to
      the Banff'97 classification, of protocol biopsies before and at 3, 12, and 36
      months after transplantation, as well as GFR at 1, 3, 12, 36, and 60 months and
      MPA enzyme-linked immunosorbent assay, MPAG (HPLC/UV) C(0) levels at 7 days as
      well as at 1, 3, 12, and 36 months. RESULTS: We observed nonlinear, significant
      correlations between MPA, MPAG C(0) levels and subclinical rejection episodes
      (SCR) according to chronic interstitial changes (ci), chronic tubulitis (ct),
      arteriolar hyalinization (ah) and chronic allograph nephropathy (CAN) indices in
      protocol biopsies. MPA C(0) levels below 1.0 to 1.5 microg/mL at day 7 were
      associated with an increased risk of SCR (P < .03), ci > or = 2 (P < .05), CAN >
      or = 2 (P < .04), and ah > or = 2 (P < .07). MPAG C(0) levels above 100 to 150
      microg/mL at day 7 were associated with a decreased risk of ct > or = 2 (P <
      .01), ci > or = 2 (P < .04), or CAN > or = 2 (P < .04). We also observed a
      significant linear positive correlation between MPA C(0) level and a significant
      negative correlation between MPAG C(0) level at 1 month with GFR. CONCLUSION:
      Optimal MPA and MPAG exposure in the early posttransplant period may improve
      renal graft outcomes.

PMID- 19857668
TI  - Estimated glomerular filtration rate evolution between 6 and 24 months predicts
      long-term kidney transplant survival among patients with inferior graft function.
AB  - One-year serum creatinine and other clinical and immunologic factors remain
      uncertain predictors of long-term kidney allograft outcomes. The aim of our
      retrospective study was to evaluate the prognostic significance of the estimated
      glomerular filtration rate (eGFR) monitoring of patients with suboptimal kidney
      allograft function. The analysis included 332 patients (median age, 43 years),
      who received deceased donor kidney transplantations between 1995 and 2007 with
      graft function for at least 1.5 years (median follow-up, 7 years). We examined
      the eGFR (the 4-variable Modification of Diets in Renal Disease [MDRD] equation)
      at 6 month posttranspant and every 6 months thereafter. Based on eGFR
      stratification (>60, 50-60, 40-49, and <40 mL/min per 1.73 m(2)) at 6 months we
      divided the patients into 4 groups. We identified patients with eGFR improvement
      (as judged by >20% increment between 6 and 24 months), versus stable or declining
      eGFR courses. RESULTS: Among the groups, the eGFR improved among 47% of patients.
      Demographic characteristics including time on dialysis, human leukocyte antigen
      matching, cold ischemia times were similar across groups. A greater incidence of
      disadvantageous characteristics was observed among the deteriorating groups:
      older donor, higher delayed graft function incidence, as well as more frequent
      and severe acute rejection episodes. Excellent and comparable 5-year graft
      survivals were noticed among patients with improved eGFR between 6 and 24 months
      (97%, 100%, 100%, 94%). CONCLUSION: Assessment of eGFR was a valuable biomarker
      for long-term kidney transplant outcomes among patients with inferior renal
      transplant function. A tendency to improve eGFR between 6 and 24 months
      posttransplant was advantageous for graft survival, possibly indicating state of
      immunologic quiescence.

PMID- 19857669
TI  - Is external jugular venous pressure a good predictor of volume status in kidney
      graft recipients?
AB  - To ensure appropriate function of the transplanted organ, it is necessary to
      adequately maintain vascular volume during the kidney transplantation procedure.
      For this purpose, central venous pressure (CVP) is monitored through a catheter
      inserted into the superior vena cava (SVC). Central venous cannulation is
      associated with a risk of serious complications. An objective of this study was
      to investigate whether there was a correlation between pressures measured in the
      SVC and in the external jugular vein (EJV). We studied 33 chronically dialyzed
      patients who had a short catheter placed in the EJV because of difficulties in
      peripheral vein cannulation in the limbs. In each case, general anesthesia was
      induced and a central catheter inserted into the SVC. Every 10 minutes venous
      pressure measurements were obtained simultaneously at both sites. A significant
      (P < .001) correlation was observed between external jugular vein pressure (EJVP)
      and CVP. CVP could be described as a function of EJVP by the equation CVP =
      {0.90299 x EJVP} - 0.8361. The results of this study indicated that monitoring
      the EJVP allows equally efficient evaluation of vascular volume as the CVP. In
      our opinion, EJVP is sufficient to evaluate vascular volume during kidney
      transplantation in patients with difficult vascular access.

PMID- 19857670
TI  - Association of the A1936G (rs203462) of A-kinase anchoring protein 10
      polymorphisms with QT interval prolongation during kidney transplantation.
AB  - INTRODUCTION: The purpose of this study was to investigate whether the
      polymorphism in the kinase-binding domain of A-kinase anchoring protein 10
      (AKAP10) was related to the risk of occurrence of potentially dangerous
      arrhythmias during kidney transplant. METHODS: We performed this prospective
      observational study with additional patient monitoring during the kidney
      transplant procedure and in the postoperative period with continuous
      electrocardiogram (ECG) - (digital holter; ECG monitor type 300-7 Suprima system;
      Oxford, UK). After manual trace analysis, we performed classification of
      arrhythmias by interval measurement (including QT correction according to
      Bazett's formula: Qtc = QT/RR1/2), ST segment analysis within all channels, and
      analysis of heart rate variability (HRV) parameters (time analysis: SDNN as total
      rate variability measure, SDANN as long-term variability measure, SDNNindex,
      rMSSD and pNN50 as short-term variability measure) as well as frequency measure
      of power width parameters in the spectrum between 0.0033 Hz and 0.4 Hz.
      Subsequently applying polymerase chain reaction restriction fragment length
      polymorphism methods, we investigated A1936G (rs203462) AKAP10 polymorphism among
      54 kidney recipients. RESULTS: Analysis of variance showed that prolongation of
      the QTc interval associated with the variant genotypes (GG + AG) was
      significantly greater compared with the AA genotype among kidney recipients (P =
      .04). We did not observe a relationship between the AKAP10 polymorphism and other
      arrhythmias, or clinical or environmental factors. CONCLUSIONS: Our data
      suggested that the AKAP10 (rs203462) GG + AG variation was associated with an
      increased risk of severe arrhythmias during kidney transplantation.

PMID- 19857671
TI  - Factors predisposing to urinary tract infections in adult kidney allograft
      recipients with lower urinary tract reconstruction.
AB  - OBJECTIVE: Urinary bladder augmentation or urinary diversion may be necessary for
      successful kidney transplantation in cases of serious urinary tract dysfunction.
      Patients with reconstructions of the urinary collecting system show noninferior
      graft survival, although urinary tract infections (UTI) may threaten kidney and
      recipient survivals. Herein we sought to identify risk factors for serious UTIs
      in cases of urinary collecting system reconstructions and to evaluate kidney
      survival and function. PATIENTS AND METHODS: This prospective, case-controlled
      study included 24 kidney allograft recipients with urinary tract reconstructions
      who were engrafted from 1999 to 2008. As controls we selected recipients of
      standard kidney transplants who were matched (1:3) for sex, age, donor type,
      procedure date, and immunosuppressive regimen. RESULTS: At posttransplantation
      33.6 +/- 28 months follow-up, kidney allograft survival was 83% among the
      reconstructed and 97% among the control groups (P = NS). Kidney allograft
      function at 3 months in the reconstruction group showed estimated glomerular
      filtration rate (eGFR) calculated by the Cockcroft-Gault (C-G) equation of 70.4
      +/- 20.8 vs 78.8 +/- 19.2 mL/1.73 m(2) in controls (P = .39), and at the end of
      follow-up, 66.3 +/- 18.1 vs 77.1 +/- 18.9 mL/1.73 m(2), respectively (P = .26).
      Urinary tract reconstruction patients experienced UTI in 91.7% of cases (n = 22)
      vs 45.6% in controls (n = 31; P < .0001). A necessity for in-hospital treatment
      was observed in 67% vs 28% of cases (P < .001). Urosepsis occurred in 4 study
      patients and 4 controls (P = NS). We observed an increased risk for serious UTI
      and a trend to diminished graft function (odds ratio [OR] = 1.6 per 10 ml/min of
      eGFr C-G; 95% confidence interval (CI) 0.97-2.77; P = .055; and OR = 14.7 per 1
      mg/dL of serum creatinine; 95% CI 0.61-352.3; P = .097). Another predictor for
      UTI was cytomegalovirus disease (CMV). CONCLUSION: Kidney recipients requiring
      urinary tract reconstructions additionally benefit from obtaining the best
      quality allografts and CMV prophylaxis.

PMID- 19857672
TI  - Risk factors for septic complications in kidney transplant recipients.
AB  - INTRODUCTION: Septic complications following kidney transplantation are a leading
      cause of therapeutic failure. An early diagnosis may protect the recipient from
      the severe consequences of sepsis. We sought to determine the risk factors
      influencing the occurrence of septic complications among kidney transplant
      recipients. MATERIALS AND METHODS: The 146 potential donors included in the study
      were evaluated for brain stem death criteria. Supportive management included
      mechanical ventilation to normocapnia, rewarming, as well as fluid and
      electrolyte replacement. Dopamine infusions and desaminovasopressin were titrated
      to predetermined mean arterial pressure (MAP). Central venous pressure (CVP) was
      maintained at 8 to 11 mm Hg. Hemodynamic data were acquired by the thermodilution
      method prior to organ procurement: MAP, CVP, pulmonary capillary wedge pressure
      (PCWP), and systemic vascular resistance index (SVRI). Recipient data included
      age, gender, period of prior hemodialysis, panel reactive antibodies, cold
      ischemia time, and cause of renal insufficiency. The 232 kidney recipients were
      examined for occurrence of septic complications including septicemia, pneumonia,
      peritonitis, or graft infection. RESULTS: Kidney transplants from donors with MAP
      < 70 mm Hg and SVRI < 1200 dyne x s/cm(5) x m(2) showed a significantly higher
      occurrence of septic complications in recipients (P < .05) where mortality rate
      was also significantly greater (P < .01). CONCLUSIONS: MAP < 70 mm Hg and SVRI <
      1200 dyne x s/cm(5) x m(2) among organ donors predicted greater occurrence of
      septic complications and increased mortality among kidney transplant recipients.

PMID- 19857673
TI  - Anemia and erythrocytosis after kidney transplantation: a 5-year graft function
      and survival analysis.
AB  - INTRODUCTION: Both anemia and erythrocytosis frequently occur after kidney
      transplantation. The aim of this study was to analyze the influence of both
      anemia and erythrocytosis on kidney graft function and long-term patient outcomes
      following kidney transplantation. PATIENTS AND METHODS: Three hundred eight-five
      consecutive patients with at least 12 months of follow-up after successful kidney
      transplantation were enrolled into this study. Of the total, 88.3% of patients
      completed a 5-year follow-up. Anemia occurred in 30.4% of patients (with 17.7%
      showing a hemoglobin concentration (Hb) <11.0 g/dL), whereas erythrocytosis was
      observed in 19.0% of patients, including 9.6% with hematocrit (HTC) >55%. We also
      analyzed graft function every 6 months after transplantation for the impact of
      anemia or erythrocytosis on the 5-year risk of patient death or graft loss.
      RESULTS: In 57.3% of anemia patients the Hb did not reach the normal range during
      the observation time. The mean eGFR-Modification of Diet in Renal Disease (MDRD)
      at 12 months after transplantation was significantly lower among patients with
      anemia: 43.9 mL/min/1.73 m(2) (39.5-48.4) vs 55.3 mL/min/1.73 m(2) (53.0-57.6; P
      < .001). Better 12-month graft function was observed among patients with
      erythrocytosis, namely, 57.7 mL/min/1.73 m(2) (53.5-62.0). Anemia but not
      erythrocytosis was associated with an increased risk of graft loss (hazard ratio
      [HR] = 4.11 [95% confidence interval (CI) 2.02-8.37]; P < .001). CONCLUSION:
      Anemia after transplantation was associated with worse kidney graft function and
      was a strong predictor of graft loss. Erythrocytosis occurs among patients with
      excellent allograft function; when properly treated it did not increase the risk
      of graft loss or death.

PMID- 19857674
TI  - Hyperuricemia is a mediator of endothelial dysfunction and inflammation in renal
      allograft recipients.
AB  - BACKGROUND: Hyperuricemia is common in renal transplant recipients treated with
      calcineurin inhibitors. Uric acid induces glomerular hypertension, microvascular
      disease, and renal interstitial fibrosis and is an independent risk factor for
      cardiovascular complications. The mechanisms by which uric acid injures renal
      allografts and the cardiovascular system remain unclear. OBJECTIVE: To assess the
      influence of uric acid on biomarkers of endothelial dysfunction and inflammation
      in renal allograft recipients. PATIENTS AND METHODS: The study included 78
      allograft recipients with normal allograft function. Exclusion criteria were
      abnormal renal function, proteinuria, diabetes mellitus, obesity, and
      inflammation. Participants were divided into 2 groups: 48 patients with
      hyperuricemia (mean [SD] uric acid concentration, 7.72 [1.33] mg/dL) and 30
      patients with normouricemia (5.48 [0.92] mg/dL; control group). Concentrations of
      plasma resistin, CD146, and soluble vascular cell adhesion molecule-1 (sVCAM-1),
      which are markers of endothelial dysfunction and inflammation, were assessed in
      both groups. No significant differences were noted for patient demographic data
      including age, sex, cause of renal failure, number of HLA mismatches, delayed
      graft function, and number of acute rejection episodes. RESULTS: Concentrations
      of the examined biomarkers were increased in the group with hyperuricemia
      compared with the control group: plasma resistin, 7.15 (2.42) ng/mL vs 6.29
      (2.76) ng/mL; CD146, 389.7 (150.0) microg/mL vs 330 (117) microg/mL; and sVCAM-1,
      1126 (371) ng/mL vs 955 (269) ng/mL (P < .03). In addition, resistin correlated
      significantly with sVCAM-1 (P < .01). CONCLUSIONS: Hyperuricemia mediates
      endothelial dysfunction and inflammation and via this pathway, possibly
      contributes to chronic allograft injury and cardiovascular events in renal
      allograft recipients.

PMID- 19857675
TI  - A possible role of hepcidin in the pathogenesis of anemia among kidney allograft
      recipients.
AB  - Hepcidin is a small, defensin-like peptide whose production by hepatocytes is
      modulated in response to anemia, hypoxia, or inflammation. We studied
      correlations of hepcidin concentrations with markers of iron status,
      erythropoietin therapy, and markers of inflammation among 130 kidney allograft
      recipients. In addition, we assessed the prevalence of anemia and its relation to
      hepcidin. Soluble receptor of transferrin (sTfR), high-sensitivity C-reactive
      protein (hsCRP), TNF-alpha, interleukin (IL)-6, prohepcidin, and hepcidin were
      measured using commercially available kits. According to the WHO definition, the
      prevalence of anemia was 28%. Among anemic recipients we found a significantly
      higher values of serum creatinine, serum prohepcidin, hepcidin, (hsCRP), TNF
      alpha, IL-6, ferritin, and proteinuria in addition to more frequent use of
      rapamycin and significantly lower use of CSA with lower CSA concentrations, as
      well as lower cholesterol, hemoglobin, and estimated glomerular filtration rate
      (eGFR) (by the Modification of Diet in Renal Disease equation). Serum prohepcidin
      significantly correlated with creatinine, GFR, time after transplantation,
      albumin, hsCRP, IL-6, and TNF-alpha, whereas hepcidin-25 correlated with serum
      iron, ferritin, hsCRP, IL-6, hemoglobin, transferrin saturation (TSAT),
      creatinine, and GFR. Multiple regression analysis showed that prohepcidin was
      independently related only to GFR and ferritin. Upon multiple regression
      analysis, predictors of serum hepcidin were eGFR, ferritin, and hsCRP, explaining
      79% of the variation of hepcidin values. In conclusion, the prevalence of anemia
      was relatively high among a population of kidney allograft recipients. The
      pathogenesis of anemia is mulitfactorial. Elevated hepcidin levels among kidney
      transplant recipients may be due to low-grade inflammation, which is frequently
      encountered in this population, and mainly to impaired renal function, but it did
      not seem to be a major pathogenetic factor for anemia in this population.

PMID- 19857676
TI  - Recipient genetic determinants of inflammatory process and nonstandard
      atherosclerosis risk factors affect kidney graft function early
      posttransplantation.
AB  - We analyzed the connections between recipient genetic features and 12-month graft
      function. The gene polymorphisms of myeloperoxidase (MPO), interleukin (IL)
      1beta, IL-6, C-reactive protein (CRP), fetuin A, and homocysteine and their gene
      product concentrations were correlated with 12-month kidney transplant function.
      The 125 kidney recipients had at least 12 months of follow-up (average, 30.9 +/-
      13.0 months). IL6-174G/C, IL1beta 3954C/T, MTHFR 677C/T, MTHFR 1298A/C, AHSG 1/2
      SNPs were determined using SSP-polymerase chain reaction (PCR) and MPO-463G/A and
      CRP- 390C/T/A with RLFP analysis. Enzyme-linked immunosorbent assay (ELISA) was
      applied to estimate MPO, fetuin A, IL-6, and IL-1beta; FPIA was applied for L
      homocysteine concentrations. The highest CRP values were linked to the presence
      of the TT genotype. We observed a positive correlation of CRP concentrations and
      GFR. Lower fetuin A concentrations were linked to the 256Ser allele, and higher
      levels to better graft function. Worse graft function was inversely associated
      with serum homocysteine concentrations. Two polymorphisms (CRP and fetuin A)
      showed functional consequences in recipients. None of the examined genetic
      determinations influenced long-term graft function. Higher values, although still
      within the normal range of CRP concentrations on the day of transplantation and 3
      months thereafter, were related to greater values of eGFR at 12 months,
      suggesting that the higher intensity of the inflammatory reaction may be a
      manifestation of more effective healing of an ischemia reperfusion injury. Both
      homocysteine and fetuin A showed long-term prognostic importance.

PMID- 19857677
TI  - Evolution of bone disease at 2 years after transplantation: a single-center
      study.
AB  - Posttransplant bone disease is caused by renal osteodystrophy. We sought to
      examine bone mineral density (BMD) among 90 renal allograft recipients of mean
      age 42.7 +/- 11.4 years to identify factors preventing bone loss at 2 years
      posttransplant. Subjects treated with cyclosporine or tacrolimus plus
      azathioprine/MMF and prednisone underwent BMD estimates of the lumbar spine (LS)
      and of the proximal femur using dual energy x-ray absorptiometry (DEXA) at 3
      months and every 6 months for 2 years. We assayed markers of bone remodeling:
      intact parathyroid hormone (iPTH), calcitriol, osteocalcin, and carboxyterminal
      telopeptide of type I collagen on day 3, as well as month 1 and every 6 months
      after transplantation. At the initial measurement, we observed osteopenia (OSP)
      among 35% in the LS and 52% in the femur: there was osteoporosis in 8.3%. The
      prevalence of OSP increased during the first year, thereafter decreasing to the
      initial value, but the rate of osteoporosis did not change significantly (8.3% vs
      6.0%). BMD and Z-score decreased during the first and increased in the second
      year; 27% of patients regained initial values and 38% higher ones. BMD gains in
      the LS and femur were observed among subjects with higher calcitriol levels
      during the first 6 months (P < .01), higher osteocalcin (P < .05), higher
      estimated glomerular filtration rate during 1-24 months and in the tacrolimus
      group. Improvement of LS BMD occurred in younger patients (38 vs 46 years; P <
      .027); BMD gain in the femur correlated with higher levels of iPTH from 1-12
      months (P < .01). The tacrolimus group showed higher Z-scores in the LS and femur
      at 24 months (P < .05). Two years after transplantation >60% of recipients showed
      stabilization or gain in bone mass. A sufficient calcitriol level in the early
      transplant period, an adequate iPTH, good renal function, and tacrolimus therapy
      prevented BMD disease progression.

PMID- 19857678
TI  - Serum concentration of vitamin D and parathyroid hormone after living kidney
      donation.
AB  - BACKGROUND: Metabolic consequences resulting from loss of renal mass in living
      kidney donors remain uncertain. There is recent focus on the changes in the
      active form of vitamin D because it is an agent for cancer regulation. The
      objective of the study was to measure serum concentrations of 1,25
      dihydroxycholecalciferol, parathyroid hormone and insulin-like growth factor-1
      (IGF-1) in living donors after kidney donation. PATIENTS AND METHODS: Forty
      living kidney donors reported for follow-up visits. Their mean age was 46.14
      years. They were women in 52.5% of cases. The mean observation period was 65.6
      months. Serum 1,25(OH)2D3 and IGF-1 concentrations were measured by
      radioimmunoassay after extraction. Serum intact parathyroid hormone (PTH) was
      quantified using an enhanced chemiluminescence immunoassay system. RESULTS: 1,25
      dihydroxycholecalciferol deficiency in 57.5% patients after nephrectomy was the
      most important change we noted. No correlation was observed between 1,25(OH)2D3
      and PTH. A decreased serum IGF-1 concentration was observed in 17.5% of donors.
      However, decreases in both serum IGF-1 and 1,25(OH)2D3 concentrations were
      observed in 12.5% of donors. CONCLUSION: Prospective studies may be essential to
      determine metabolic changes after nephrectomy among living kidney donors.

PMID- 19857679
TI  - Inadequate blood pressure control in most kidney transplant recipients and
      patients with coronary artery disease with and without complications.
AB  - BACKGROUND: Hypertension is a widely accepted risk factor for coronary artery
      disease (CAD), chronic heart failure, and chronic kidney disease (CKD). In kidney
      transplant recipients, the prevalence of hypertension is 60% to 80%. OBJECTIVE:
      To assess the prevalence of target blood pressure in 2 high-risk populations:
      patients with CAD and kidney allograft recipients. PATIENTS AND METHODS: The
      study included 520 patients with CAD and 150 kidney allograft recipients. In the
      CAD population, 30% of patients had diabetes mellitus and 33% had CKD. In kidney
      allograft recipients, 52% had diabetes (15%) or CKD. Hypertension was diagnosed
      and treated in 72% of patients with CAD and 90% of kidney allograft recipients.
      In the CAD population without diabetes but with CKD, target blood pressure was
      achieved in 47% compared with 31% in the CKD population. Treatment included
      angiotensin-converting enzyme (ACE) inhibitors in 72% of patients, calcium
      channel blockers in 28%, diuretic agents in 27%, and beta-blockers in 89%. In
      allograft recipients, more than 60% required 3 or more hypotension agents. Only
      40% demonstrated target blood pressure. In the latter group, the most commonly
      used hypotension agents were ACE inhibitors in 38%, calcium channel blockers in
      84%, diuretic agents in 51%, beta-blockers in 68%, and alpha-blockers in 15%.
      CONCLUSION: Both cohorts demonstrated a high prevalence of hypertension. Despite
      polytherapy, optimal blood pressure control was not achieved in most patients.
      Greater efforts should be expended to optimize blood pressure control, in
      particular in the presence of comorbidities. In transplant recipients, beta
      blockers are widely used, whereas ACE inhibitors are used infrequently.

PMID- 19857680
TI  - Minimally invasive methods for the treatment of lymphocele after kidney
      transplantation.
AB  - BACKGROUND: One common complication after kidney transplantation is a lymphocele.
      The aim of our work was an analysis of incidence of lymphocele and the
      effectiveness of minimal invasive methods in the management of this complication.
      MATERIALS AND METHODS: The examined group was consisted of 158 patients (68
      female and 90 male) with end-stage renal disease who underwent kidney
      transplantation. RESULTS: Twenty-one patients (13%) developed symptoms of
      lymphocele after transplantation procedure within an average time of 34 weeks.
      The clinical symptoms included a decrease in 24-hour urine collection, an
      increase in plasma creatinine concentration, abdominal discomfort, lymphorrhea
      with a surgical wound dehiscence, voiding problems of urgency or vesical
      tenesmus, febrile states, or symptoms of deep vein thrombosis. The following
      methods were applied with variable efficacy: aspiration with recurrence 75%;
      percutaneous drainage with 55%, effectiveness; laparoscopic fenestration with 72%
      satisfactory outcomes (1 patient presented an excessive bleeding after the
      procedure), and classic surgery with favorable results. CONCLUSION: Percutaneous
      drainage guided by ultrasonic imaging should be recommended as the first attempt
      to cure a lymphocele. Laparoscopy is a feasible, safe technique that should be
      used after unsuccessful percutaneous drainage. A larger series of patients is
      required to confirm the superiority of minimal invasive methods to the classical
      approach.

PMID- 19857681
TI  - Results of treatment of acute liver failure patients with use of the prometheus
      FPSA system.
AB  - OBJECTIVE: Herein we have presented the results of treatment of acute liver
      failure (ALF) patients with the use of the Prometheus FPSA dialysis system.
      MATERIALS AND METHODS: To January 2009, we performed 278 FPSA procedures in 114
      patients, including 52 experience and ALF. The patients who underwent the FPSA
      procedure consisted of 32 women and 20 men of overall mean age of 33 +/- 12
      years. The causes of ALF were: Wilson's disease (n = 15), unknown origin ALF (n =
      11), amanita phalloides intoxication (n = 7), paracetamol intoxication (n = 8),
      acute hepatitis B virus (HBV)/hepatitis C virus (HCV) infection (n = 7), liver
      insufficiency after parenchymal resection (n = 2) drug reaction with eosinophilia
      and systemic symptoms (DRESS) syndrome (n = 1), rabdomyolysis (n = 1), or primary
      nonfunction (PNF) after orthotopic liver transplantation (OLT) (n = 1). All
      procedures were performed using the Prometheus 4008H Fresenius Medical Care liver
      support system. The average number of treatments per patient was 2.41 and the
      average time for each FPSA treatment was 6.3 hours. The average heparin dose used
      during the procedure was 750 IU/h. RESULTS: After the whole treatment regimen, we
      observed significant improvements in the biochemical results. The average
      concentrations improved: serum ammonia (before 249.2 mug/dL versus after 109.7
      mug/dL); serum bilirubin (before 21.53 mg/dL versus after 8.81 mg/dL), serum
      aspartate aminotransferase (AST; before 2456.4 U/L versus after 1068.8 U/L);
      serum alanine aminotransferase (ALT; before 2958.2 U/L versus after 1595.8 U/L);
      serum urea (before 58.5 mg/dL versus after 21.1 mg/dL); serum creatinine (before
      2.9 mg/dL versus after 1.7 mg/dL); and pH value (before 7.11 versus after 7.32).
      After Prometheus treatment OLT was performed in 33 patients. Among the 28 who
      survived (53.8%), 22 underwent OLT and 6 did not have OLT. Among the 24 patients
      who died (46.2%), 13 were before OLT and 11 after OLT. CONCLUSION: The Prometheus
      4008H Fresenius Medical Care Liver support system was useful method of
      detoxification for patients with ALF, serving as an element of pretransplantation
      care.

PMID- 19857682
TI  - Upper gastrointestinal endosonography in patients evaluated for liver
      transplantation.
AB  - BACKGROUND: Endosonography (EUS), which merges endoscopic and ultrasound
      examinations, is a useful modality to display abnormal vessels that develop in
      the intrinsic circulation, frequently called "deep" varices. If these
      pathological veins exceed of 5 mm diameter, they significantly increase the risk
      of bleeding among patients with cirrhosis. In the most recent pilot study EUS
      proved useful to assess children for orthotopic liver transplantation (OLT). AIM:
      We performed a cross-sectional study of EUS on 33 (22 males and 11 females) adult
      cirrhotic subjects being assessed for OLT. MATERIALS/METHODS: We used an
      echoendoscope at 7.5 MHz/12 MHz/20 MHz to evaluate the esophagus and stomach,
      including "deep" periesophageal/perigastric varices (adjacent to the muscularis
      propria) and paraesophageal/paragastric varices (outside the muscularis propria).
      "Deep" varices were considered to be large if >5 mm. RESULTS: On endoscopy, 26
      (79%) patients showed esophageal varices (EV), including 11 (33%) with large (>5
      mm) varices. Gastric varices (GV) were observed in 13 (39%) subjects, with 3
      patients displaying large (>5 mm) varices. On EUS large "deep" EV (both para and
      periesophageal) were observed in 12 (36%) subjects, among whom 5 (42%) did not
      have large varices on endoscopy. Large "deep" GV were found on EUS in 12 (36%)
      subjects. On endoscopy 4 of them (33%) showed no varices and 3 (25%) had small
      GV. CONCLUSIONS: EUS offers a precise evaluation of portal hypertension in OLT
      candidates. "Deep" potentially dangerous varices, which are undetected with
      routine endoscopy, were noted in a significant proportion of patients. The role
      of EUS in prioritizing subjects for OLT must be evaluated in a prospective study.

PMID- 19857683
TI  - Vitreous amyloidosis in two sisters as the indication of transthyretin-related
      familial form of systemic amyloidosis among liver transplantation candidates.
AB  - Vitreous amyloidosis, a rare condition characteristic of the familial form of
      systemic amyloidosis with polyneuropathy, is caused by a mutation in the
      transthyretin (TTR) gene. Herein we have presented 2 sisters with involvement of
      the vitreous body, which prompted a subsequent diagnosis of the TTR-related,
      familial form of systemic amyloidosis. Due to the progressive character of the
      disease and poor prognosis, the patients have been considered for liver
      transplantation, which at present is the only treatment option for this disease.

PMID- 19857684
TI  - Administration of a recombinant factor Vlla in patients undergoing liver
      transplantation for fulminant hepatic failure.
AB  - BACKGROUND: Fulminant hepatic failure (FHF) is associated with profound clotting
      disturbances leading to the risk of a major blood loss during orthotopic liver
      transplantation (OLT). Application of a recombinant factor VIIa (rVIIa) that
      promptly corrects clotting abnormalities remains controversial in the OLT
      setting. We conducted a retrospective analysis of the effect of rVIIa on the
      prothrombin time (PT) and other perioperative parameters in patients transplanted
      for FHF in our center. MATERIALS AND METHODS: Nineteen consecutive patients (9
      males/10 females) of overall mean age of 33 +/- 13 years underwent the procedure
      due to: Wilson's (n = 8), non-A-non-B hepatitis (n = 6) or Amanita phalloides
      toxicity (n = 5). All subjects received rVIIa at a mean dose of 54 +/- 16
      microg/kg body weight at 10 minutes before the skin incision. The PT was measured
      at 15 minutes and 12 hours after injection. Data were analyzed with StatView
      program with P < .05 considered significant. RESULTS: Rapid correction of PT was
      observed in all patients: the mean PT before injection was 37 +/- 14 versus 14 +/
      3 after 15 minutes (P < .0001). Twelve hours after the injection the PT was 19
      +/- 5 (P < .0001 vs before injection and P < .0007 vs 15 minutes after
      injection). Two patients died at 1 and 4 days after OLT. Mean red blood cell
      requirement was 5 +/- 4 U and fresh frozen plasma was 11 +/- 5 U. The mean
      operative time was 527 +/- 126 minutes and intensive care unit stay 8 +/- 9 days.
      None of the patients developed thromboembolic complications. CONCLUSION:
      Administration of rVIIa caused a rapid improvement in the PT shortly after
      injection. It was safe and not associated with any thromboembolic events in our
      series.

PMID- 19857685
TI  - Correlation between selected prognostic factors and postoperative course in liver
      transplant recipients.
AB  - AIM: The objective was to identify the major prognostic factors influencing liver
      function after transplantation that predict the postoperative course and long
      term survival among liver transplant recipients. We analyzed the results of
      biochemical, microbiological, serologic, and pathologic studies of the donor and
      recipient, as well as intraoperative data. MATERIALS AND METHODS: Of 542 liver
      transplant recipients, 215 (39.7%) were analyzed in the period from 1989 to 2006.
      Patients were divided according to the mechanism leading to the liver disease:
      group I, hepatitis C virus (HCV) infection (n = 80, 37.0%); group II, hepatitis B
      virus (HBV) infection (n = 33, 15.0%); group III, HBV and HCV infection (n = 13,
      6.0%); group IV, alcoholic liver disease (ALD) (n = 66, 31.0%); and group V,
      autoimmune hepatitis (AIH) (n = 23, 11.0%). RESULTS: Prediction of patient
      survival based on clinical parameters showed a better prognostic value than that
      based only on liver function tests. Transplant urgency scores-Model for End-Stage
      Liver Disease (MELD), delta MELD and United Network for Organ Sharing (UNOS)
      enabled us to predict early and long-term patient survival after liver
      transplantation. Update of these scores, reflecting the patient's condition,
      enabled us to evaluate pretransplant life-threatening factors and urgency level.
      Organ donation predictive factors were age, viral status, and degree of liver
      steatosis. Cold and warm ischemia times still were major prognostic factor.
      Routine biliary drainage resulted in worse long-term survival than non-drained
      patients. Liver transplantation for ALD showed the highest complication rate.
      Chronic liver rejection occurred more frequently in the AIH transplanted group.
      The most useful predictive factors for 1-year survival were urea/creatinine and
      liver function tests: aspartate and alanine aminotransferases, gamma-glutamyl
      transpeptidase the International normalized ratio, and Quick. CONCLUSION: The
      prognosis of patient outcomes after liver transplantation based on clinical
      parameters showed greater value than evaluation of the laboratory data.

PMID- 19857686
TI  - Safety and efficacy of steroid-free immunosuppression with tacrolimus and
      daclizumab in liver transplant recipients: 6-year follow-up in a single center.
AB  - BACKGROUND: Avoidance of steroid therapy after solid-organ transplantation has
      become a major challenge. Corticosteroid (CS)-free maintenance immunosuppression
      not only eliminates the well-known adverse effects but also may improve long-term
      outcome. OBJECTIVE: To investigate whether a CS-free regimen of tacrolimus (Tac)
      in combination with daclizumab (Dac) induction therapy provides adequate coverage
      after orthotopic liver transplantation. PATIENTS AND METHODS: This 6-year, single
      center, retrospective study included 25 liver transplant recipients randomized to
      a Tac/CS regimen (n = 18) vs a Tac/Dac regimen (n = 7) according to the protocol
      of the MASTER (Monoclonal Antibodies vs STERoids) Study. RESULTS: No significant
      difference was observed in patient and graft survival between treatment arms:
      94.4% in the Tac/CS group vs 71.4% in the Tac/Dac group. The incidence of biopsy
      proved acute rejection episodes was 23.5% in the Tac/CS group vs 14.3% in the
      Tac/Dac group (P = NS). Total duration of hospitalization did not differ
      significantly between groups: 46.5 days in the Tac/CS group vs 73.9 days in the
      Tac/Dac group. Liver function as estimated using serum alanine aminotransferase
      and aspartate aminotransferase activity and bilirubin concentration, was not
      significantly different between the groups during 5 years posttransplantation.
      However, after 6 years, alanine aminotransferase activity was significantly
      greater in the Tac/Dac group compared with the Tac/CS group. CONCLUSIONS: A CS
      free regimen of Tac/Dac is as effective as Tac/Cs in achieving good patient and
      graft survival. However, no substantial benefits insofar as the safety of Tac/Dac
      therapy were evident during long-term follow-up.

PMID- 19857687
TI  - Immunosuppression with low-dose daclizumab in liver transplant recipients with
      impaired kidney function: a single-center experience.
AB  - BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNI) may exert detrimental
      effects, particularly in orthotopic liver transplantation (OLT) patients with
      impaired kidney function. Immunosuppression with daclizumab permits delayed
      introduction of CNI, and may be preferred for patients with kidney dysfunction.
      This retrospective analysis of our experience using daclizumab was performed
      among patients who underwent transplantation with impaired kidney function.
      METHODS: We analyzed 168 patients. A serum creatinine (Cr) level >1.5 mg/dL was
      the indication for a protocol with low-dose daclizumab (50 mg intravenous [IV],
      day 0 and day 4), mycophenolate mofetil (MMF; 500 mg twice daily IV/orally), and
      tapering doses of prednisolone from day 0 after OLT. CNI were introduced at day 4
      15 after OLT. Patients with a Cr level <1.5 mg/dL received immunosuppression with
      CNI+MMF+steroids or CNI+steroids. RESULTS: Fourteen patients fulfilled the
      criterion for daclizumab immunosupression. Their Cr and creatinine clearance
      (CrCl) values at OLT were 2.85 +/- 1.22 mg/dL and 19 +/- 11 mL/min, respectively.
      In the remaining 154 patients, Cr and CrCl results were 0.88 +/- 0.3 mg/dL and
      107 +/- 82 mL/min, respectively. At discharge, the daclizumab group showed Cr and
      CrCl estimates of 0.97 +/- 0.45 mg/dL and 86 +/- 34 mL/min (P < .0001 for both,
      when compared with prior to OLT). Both Cr and CrCl levels at discharge were not
      different from those values of patients who underwent transplantation with normal
      kidney function. The incidence of acuterejection was 14% in the daclizumab group
      and 18% in the other recipients (P = not significant [NS]). CONCLUSIONS:
      Immunosuppression with low-dose daclizumab and delayed introduction of CNI was
      safe and did not increase the risk of an acute rejection episode, thus offerring
      an excellent therapeutic option for patients who undergo transplantation with
      impaired kidney function.

PMID- 19857688
TI  - Prediction of graft loss and death in patients with primary sclerosing
      cholangitis.
AB  - BACKGROUND: The prognosis of patients with primary sclerosing cholangitis (PSC)
      can be accurately determined using the Mayo Clinic Score (MRS), a mathematical
      model which predicts patient survival. The purpose of our study was to determine
      the risk of graft loss and/or death among patients who were listed or
      transplanted because of PSC. PATIENTS AND METHODS: We analyzed the data of 52
      patients, who were placed on the transplant list due to PSC between January 2000
      and November 2008 and either did or did not undergo liver transplantation (OLT).
      The primary end point (EP1) of the study was the patient death for any cause. The
      secondary end point (EP2) was recurrence of PSC or appearance of CCC or death
      related to the primary liver disease after OLT (PSC recurrence). The observation
      time was 60 months. According to the calculated MRS, patients were divided into 3
      groups: group A (MRS < 0.56); group B (0.56 < or = MRS < 1.56), and group C (MRS
      > 1.56). The analysis was performed using the LIFETEST and PHREG Procedures of
      the SAS System. RESULTS: The risk of EP1 occurrence was 2.0 per 1 point of MRS (P
      < .0006). The risk of EP2 was 2.1 per 1 point of MRS (P < .001). Groups B and C
      compared with group A showed risks of death of: 0.79 (P = NS) and 6.59 (P < .08),
      respectively. The percentage of 5-year patient survival rate were 94%, 94%, and
      45% according to groups A, B, and C, respectively. CONCLUSION: The risk of death
      in patients with MRS > 1.56 was 6.59-fold higher than those with MRS < 0.56. MRS
      > 1.56 significantly decreased 5 year survival among patients with primary
      sclerosing cholangitis.

PMID- 19857689
TI  - Assessment of a modified Child-Pugh-Turcotte score to predict early mortality
      after liver transplantation.
AB  - OBJECTIVE: The Model for End-Stage Liver Disease (MELD) predicts mortality on the
      transplant list; however, it has not been of much use to predict posttransplant
      outcomes. Several prognostic models have been tested among patients with
      cirrhosis; nevertheless, their predictive value has not been established in the
      posttransplant setting. We recently modified the Child-Pugh-Turcotte (CPT) score
      by adding creatinine levels (CPT + Cr), which has proven useful for patients with
      alcoholic cirrhosis. This retrospective analysis sought to predict early (1
      month) mortality using CPT + Cr versus 5 other prognostic models in patients who
      underwent orthotopic liver transplantation (OLT) at our center. MATERIALS AND
      METHODS: We included 48 consecutive patients (30 males, 18 females, median age 51
      years). The predictive values of CPT + Cr were compared with CPT scores without
      or with the Huo modification, CPT + Na, MELD, and MESO, which is the MELD to
      serum Na ratio. Pearson correlations and ROC curves as evidenced by the area
      under the curve (AUC) were determined for each index. P < .05 was considered to
      be significant. RESULTS: CPT + Cr showed the highest correlation with the risk of
      death (r = .368, P = .01); MELD and MESO were the lowest (r = .204, P = NS; and r
      = .254, P = NS, respectively). ROC analysis showed the best predictive value of
      CPT and CPT-Crea with AUC of 0.758 (P = .010) and 0.748 (P = .011) respectively,
      as compared to 0.689 for MESO and 0.659 for MELD (both NS). CONCLUSIONS: A
      modified CPT score with creatinine levels may be of value to predict early death
      after OLT. Its usefulness must be validated in a prospective study of a large
      patient cohort.

PMID- 19857690
TI  - Modified Charlson Comorbidity Index in predicting early mortality after liver
      transplantation.
AB  - BACKGROUND: The Charlson Comorbidity Index for orthotopic liver transplantation
      (CCI-OLT) is a modified clinical score recently proposed to be useful for the
      assessment of long-term survival after OLT. It includes 9 associated conditions
      selected upon a multivariate analysis of a large cohort of transplant recipients.
      Its role in predicting early mortality after OLT has not yet been investigated.
      We sought to CCI-OLT as a potential predictor of 1-month mortality after OLT.
      MATERIALS/METHODS: One hundred ninety-seven OLT were performed in our center
      between March 2002 and February 2009. After exclusion of patients who underwent
      transplantation for fulminant hepatic failure or those who underwent regrafting,
      we included a group of 169 patients. Viral (39%) and alcohol-induced (23%)
      cirrhosis were the most common indications for OLT. The CCI-OLT index was
      assessed in all patients. RESULTS: In total, 146 (86%) subjects survived and 23
      (14%) died within 1 month after LT. Fifty-one (30%) patients suffered at least 1
      comorbidity that was included in the CCI-OLT. Direct comparison between survivor
      versus nonsurvivor groups showed no significant difference in terms of the total
      frequency of comorbidities (30.1% vs 30.4%; P > .99) or the number or the type of
      comorbidity. The most commonly associated condition in both groups was diabetes
      mellitus. CONCLUSION: Unlike the case of long-term survival, CCI-OLT did not seem
      to predict early (1-month) mortality after OLT.

PMID- 19857691
TI  - Influence of the primary disease on rehabilitation results in the early
      postoperative period in patients after orthotopic liver transplantation.
AB  - BACKGROUND: Rehabilitation after orthotropic liver transplantation (OLT) is a
      difficult clinical problem due to severe comorbidities and complications. We
      evaluated the rehabilitation progress in the early postoperative period of
      patients after OLT depending on the reason for liver transplantation. MATERIALS
      AND METHODS: We retrospectively evaluated 309 OLT recipients transplanted between
      2003 and 2006, including 161 women and 148 men. We analyzed the results of early
      postoperative rehabilitation measured by the time to full, active, erection
      upright after surgery. We divided the patients into 5 groups due to etiology of
      liver failure: group A (n = 89; mean age, 46.7 years) consisted of patients with
      liver cirrhosis due to hepatitis B, C, or both; group B (n = 70; mean age, 43.8
      years) included patients with primary biliary cirrhosis and primary sclerosing
      cholangitis; group C (n = 44; mean age, 46 years) conprised patients with
      postalcoholic liver cirrhosis; group D (n = 23; mean age, 29.7 years) had
      experienced acute or subacute liver failure; and group E (n = 83; mean age, 37.4
      years) had other reasons of liver failure. All patients were included in an
      identical rehabilitation program. RESULTS: The mean time to full, active,
      erection upright was dependent on the reason for liver failure. The best result
      was observed in groups A and E (4.51 and 4.6 days, respectively), medium in
      groups B and C (5.3 and 5.02, respectively), and worst in group D (8.5 days). The
      differences between groups A, E, and D were significant. CONCLUSION: The best
      results were obtained in groups A and E, where full, active, erection upright was
      achieved at 4.51 and 4.60 days respectively, and worst in group D, where it was
      achieved on day 8.50. These results need to be taken into account in planning the
      rehabilitation process for OLT patients. When analyzing the correlation between
      full, active, erection upright and primary diseases, one of the factors
      contributing to the delay needs to be assumed to be the inability to develop
      compensating mechanisms in the cases of acute and subacute hepatic failures,
      resulting from the sudden development of the disease.

PMID- 19857692
TI  - Prevalence and predictors of acute renal injury in liver transplant recipients.
AB  - Renal failure is a major factor impacting liver transplant outcomes. Renal
      functional impairment predicts decreased survival, leading to increased morbidity
      and mortality. The aim of this study was to estimate the incidence, risk factors,
      and resolution of acute kidney injury (AKI) among liver transplant recipients
      during the operative hospital stay. We analyzed data from 99 orthotopic liver
      transplantations (OLT) performed at our center in 2008. Posttransplantation
      occurrence of AKI was defined as an increase in serum creatinine (SCr)
      concentration of 0.3 mg/dL or more, namely, 1.5-fold from baseline. AKI was
      observed among 31.31% of liver transplant recipients (n = 31). The mean increase
      in SCr was 2.49 +/- 0.78-fold from baseline. The mean posttransplant SCr level
      was 2.59 +/- 0.92 mg/dL. Renal replacement therapy was introduced to 16.12% (n =
      5) liver recipients developing AKI. Among them, 2 subjects (6.45%) died. The mean
      SCr level at the time of discharge from the hospital was 1.17 +/- 0.57 mg/dL
      among the AKI group compared with 0.77 +/- 0.32 mg/dL among the group without
      AKI. Pretransplant renal impairment expressed by an elevated SCr concentration
      (relative risk [RR] = 1.25; P = .0386) and treatment with exogenous
      vasoconstrictors during the operation (RR = 2.27; P = .016) were identified as
      risk factors for developing AKI after liver transplantation.

PMID- 19857693
TI  - Reduction of biliary complication rate using continuous suture and no biliary
      drainage for duct-to-duct anastomosis in whole-organ liver transplantation.
AB  - Biliary complications (BC) following orthotopic liver transplantation (OLT) are
      related to various factors including surgical technique and use of biliary drains
      for a duct-to-duct (DD) anastomosis. Herein we have reported the influence of
      changes in surgical technique on BC following OLT in our center. From February
      2002 to February 2007, we performed 101 whole-organ OLT with a DD anastomosis in
      99 adults, of whom we analyzed 84 subjects. We excluded recipients who died
      within 30 days of OLT without any evidence of BC and 1 patient with a biliary
      stricture secondary to a hepatic artery thrombosis. Until late 2004, a DD
      anastomosis with interrupted sutures over an external biliary drain (DD/BD) was
      performed in 35 patients (Group I). Subsequently, no biliary drain was used for
      the DD anastomosis (DD/non-BD), using a continuous suture in 49 patients (Group
      II). The DD anastomosis with interrupted sutures over a biliary drain was
      associated with a higher incidence of both total (31% vs 8%; P = .008) and late
      BC (>30 days; 20% vs 2%; P = .008) with a trend toward more leaks (17% vs 4%; P =
      .06). All biliary leaks in patients with DD/BD reconstruction occurred at the
      exit site of the biliary drain following its removal. No significant differences
      were observed when we compared the incidence of biliary strictures and the
      necessity for surgical intervention. One patient died due to a BC. Our results
      indicated that a DD anastomosis performed with a continuous suture technique and
      no external biliary drainage reduced the incidence of BC after whole-organ OLT.

PMID- 19857694
TI  - Vascular complications following adult piggyback liver transplantation with end
      to-side cavo-cavostomy: a single-center experience.
AB  - BACKGROUND: Vascular complications remain a significant cause of morbidity, graft
      loss, and mortality following orthotopic liver transplantation (OLT). These
      problems predominantly include hepatic artery and portal vein thrombosis or
      stenosis. Venous outflow obstruction may be specifically related to the technique
      of piggyback OLT. MATERIALS AND METHODS: Between February 2002 and February 2009,
      we performed 200 piggyback OLT in 190 recipients. A temporary portacaval shunt
      was created in 44 (22%) cases, whereas end-to-side cavo-cavostomy was routinely
      performed for graft implantation. Pre-existent partial portal or superior
      mesenteric vein thrombosis was present in 17 (12%) cirrhotics in whom we
      successfully performed eversion thrombectomy, which was followed by a typical end
      to-end portal anastomosis. The donor hepatic artery was anastomosed to the
      recipient aorta via an iliac interposition graft in 31 (16%) patients. RESULTS:
      The 14 (7%) vascular complications included hepatic artery thrombosis (n = 5),
      hepatic artery stenosis (n = 3), aortic/celiac trunk rupture (n = 2), portal vein
      stenosis (n = 2), and isolated left and middle hepatic venous outflow obstruction
      (n = 1). There was also 1 case of arterial steal syndrome via the splenic artery.
      No patient experienced portal or mesenteric vein thrombosis. Therapeutic
      modalities included re-OLT, arterial/aortic reconstruction and splenic artery
      ligation. Vascular complications resulted in death of 5 (36%) patients.
      CONCLUSION: Our experience indicated that piggyback OLT with an end-to-side cavo
      cavostomy showed a low risk of venous outflow obstruction. Partial portal or
      mesenteric vein thrombosis is no longer an obstacle to OLT; it can be
      successfully managed with the eversion thrombectomy technique.

PMID- 19857695
TI  - Impact of tumor characteristic on the outcome of liver transplantation in
      patients with hepatocellular carcinoma.
AB  - INTRODUCTION: Orthotopic liver transplantation (OLT) is a well-established
      treatment for cirrhotic patients with hepatocellular carcinoma (HCC) who meet the
      Milan criteria. The aim of this study was to identify predictors of survival
      among 65 patients with HCC in cirrhotic livers who underwent liver
      transplantation (OLT). METHODS: From January 2001 to December 2008, we performed
      655 OLT in 615 patients. HCC was diagnosed in 58 patients before OLT and in 65 by
      histological examination of the explanted livers; 74% of the patients met Milan
      criteria by histological examination. RESULTS: The median follow-up was 27 months
      (range = 1-96). We analyzed patient age and gender, etiology of liver disease,
      Child score at transplantation, rejection episodes, tumor number/size, vascular
      invasion, and differentiation grade. There was no significant difference in
      survival among patients grouped according to the Model for End-stage Liver
      Disease staging system for HCC. The 5-year survival of patients with low
      differentiated (G3) HCC was significantly worse than that of those with
      moderately differentiated (G2) or well-differentiated (G1) HCC: 50%, 81%, and 86%
      respectively, (P < .01). Patients with microvascular invasion displayed a worse 5
      year survival than those without vascular invasion (42% vs 80%; P < .01).
      CONCLUSIONS: The analysis indicated that the histological grade of the tumors and
      evidences of microscopic vascular invasion were the most useful predictive
      factors for overall survival among patients with cirrhosis after liver
      transplantation for HCC.

PMID- 19857696
TI  - Low incidence of hepatic artery thrombosis after hepatic artery reconstruction
      during liver transplantation.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) remains an important cause of graft
      loss after liver transplantation. HAT can be caused by technical, hemodynamic, or
      immunologic factors. Bench reconstruction of anatomical variants of the hepatic
      artery is considered to fore a major risk related to HAT. The purpose of the
      study was to analyze the influence on HAT of hepatic artery vascular
      reconstruction. METHODS: We retrospectively analyzed 341 donor forms completed
      between January 2004 and December 2007. Vascular reconstruction was defined as an
      additional anastomosis between donor hepatic arteries, which was required to
      fully revascularize the graft. Any incident of HAT was confirmed by angiography
      and intraoperatively during retransplantation. Fisher's exact test and 95%
      confidence intervals (CI) were applied for statistical analysis. RESULTS: Among
      341 grafts hepatic artery anomalies observed, variations were recorded in 92
      cases (26.9%), of whom 35.9% required hepatic artery reconstruction. HAT was
      diagnosed in 3% (1/33) hepatic reconstructions (CI, 0.1%-15.8%) compared with
      1.6% of grafts (5/308) that did not required hepatic reconstruction (P < or =
      .45). The 1 case of hepatic thrombosis (1/59) accounting for 1.6% among the group
      with hepatic anomalies without reconstruction (CI, 0.04%-9.1%). CONCLUSION: A
      single hepatic reconstruction was a nonsignificant factor for HAT. Hepatic artery
      reconstruction did not increase the risk of HAT compared with the normal blood
      supply. Hepatic artery anomalies did not significantly increase the incidence of
      HAT compared with the group of patients without arterial variations.

PMID- 19857697
TI  - Surgical site infections in the early posttransplant period after simultaneous
      pancreas-kidney transplantation.
AB  - OBJECTIVE: This study evaluated the frequency of microbial isolates and their
      susceptibility profiles among cultures from the "surgical site" of 26
      simultaneous pancreas-kidney (SPKT) recipients in the early posttransplant
      period. PATIENTS AND METHODS: Data on microbiologic cultures of 26 adult patients
      undergoing SPKT were collected prospectively from 2001 to the end of 2006. The
      isolation and identification of cultured micro-organisms was performed according
      to standard microbiological procedures and commercially available tests.
      Susceptibility of the strains to antibacterial agents was made by the Clinical
      and Laboratory Standards Institute (CLSI) guidelines. RESULTS: All patients were
      followed prospectively for the first 4 weeks after surgery yielding 168 microbial
      isolates from the surgical site. The most commonly isolated organisms were Gram
      positive bacteria (65.5%) with domination of staphylococci (52.7%) as methicillin
      resistant S aureus and methicillin-resistant coagulase-negative staphylococci.
      The second most common were enterococci (33.6%) with the presence of an high
      level aminoglycoside-resistant strains (64.9%) and vancomycin-resistant strains
      (2.7%). Gram-negative bacteria comprised 19% of positive cultures; among them
      were isolated extended spectrum beta-lactamase producers and carbapenem-resistant
      strains. Yeast-like fungi comprised 15.5% of positive cultures. In conclusion, we
      observed predominantly Gram-positive bacteria, comprising 65.5% of isolates. The
      increased proportion of multi-drug-resistant bacterial isolates may be due to the
      frequent prophylaxis of bacterial infections in patients.

PMID- 19857698
TI  - Urinary tract infections in the early posttransplant period after simultaneous
      pancreas-kidney transplantation.
AB  - OBJECTIVE: Urinary tract infection (UTI) is among the common infection in
      simultaneous pancreas-kidney transplantation (SPKT). PATIENTS AND METHODS: The
      study included 26 adult patients undergoing SPKT between September 2001 and
      December 2006. All the patients were followed prospectively for UTI during the
      first 4 weeks after surgery. Urine samples were investigated for bacteriologic
      cultures. The micro-organisms were identified in accordance with standard
      bacteriologic procedures. Susceptibility testing was carried out using Clinical
      and Laboratory Standards Institute (CLSI) procedures. RESULTS: Among 77 urine
      specimens obtained from all recipients during the first month, there were 30
      isolated bacterial strains. The most common were Gram-positive bacteria (53.3%)
      with predominance of enterococci (75%) associated with high levels of
      aminoglycoside resistant strains (HLAR; 58.3%) and vancomycin-resistant strains
      (VRE; 25%). Gram-negative bacteria were detected in 46.7% of positive cultures.
      CONCLUSIONS: In our study, enterococci predominated as 75% of Gram-positive
      isolates. The increased proportion of multi-drug-resistant bacteria, which can
      caused severe UTI in patients after SPKT, may be due to the frequent use of
      prophylaxis of bacterial infections in patients.

PMID- 19857700
TI  - Usefulness of 16-row multidetector computed tomography with volume rendering and
      maximum intensity projection reconstruction as a monitor pancreatic graft vessel
      patency during the early postoperative period.
AB  - Thrombosis of the pancreatic graft vessels is the most common complication after
      transplantation. It leads to loss of 5% to 8% of grafts during the early
      postoperative period. The aims of this study were to evaluate the usefulness of
      16-row multidetector computed tomography (16-MDCT) with volume rendering (VR) and
      maximum intensity projection (MIP) reconstruction to monitor pancreatic graft
      vessel patency during the early postoperative period and the efficacy of a
      heparin infusion as a treatment for graft thrombosis. Among 40 consecutive
      simultaneous pancreas-kidney transplant recipients, 16-MDCT was performed at 6 to
      8 days after the operation. Secondary reconstructions were obtained with VR and
      MIP algorithms to evaluate the morphology and patency of the extra- and
      intrapancreatic arteries and veins. In cases of thrombosis, every patient was
      treated with an infusion of unfractionated heparin. In 15 recipients, thrombosis
      of the large vessels was detected by 16-MDCT. Heparin infusions saved five
      pancreatic grafts (5/15; 33.3%), but the other 10 pancreatic grafts were removed.
      In another four recipients (4/40; 10%) the thrombi were localized only in small
      intrapancreatic vessels. Treatment with heparin infusion was successful in 3/4
      (75%) cases with patent vessels upon control computed tomography examination. We
      compared the efficacy of heparin treatment depending on the diameter of the
      thrombosed vessel, observing a significant difference (5/15 vs 3/4; P < .01; chi
      square). 16-MDCT with secondary reconstruction by application of VR and MIP
      algorithms was an efficient method to visualize not only large pancreatic graft
      arteries and veins but also intrapancreatic parenchymal vessels. In cases of
      thrombosis of small intrapancreatic vessels, unfractionated heparin infusion
      significantly decreased graft loss.

PMID- 19857699
TI  - Etiologic agents of bacteremia in the early period after simultaneous pancreas
      kidney transplantation.
AB  - BACKGROUND: Bacteremia is among the known complications in simultaneous pancreas
      kidney transplantation (SPKT). This study evaluated the frequency of microbial
      isolates and their susceptibility profiles among cultures of clinical samples
      obtained from blood and from the tips of blood vessel catheters of 26 SPKT
      recipients suspected of bacteremia in the early posttransplant period. PATIENTS
      AND METHODS: Data on microbiologic blood cultures of 26 adult patients undergoing
      SPKT were collected prospectively from 2001 to the end of 2006. The isolation and
      identification of cultured microorganisms were performed according to standard
      microbiological procedures and commercially available tests. The susceptibility
      of the strains to antibacterial agents was established by the Clinical and
      Laboratory Standards Institute guidelines. RESULTS: All patients were followed
      prospectively for the first 4 weeks after surgery. Among 66 clinical samples,
      there were 23 microbial isolates from blood samples of 17 recipients and catheter
      tips of 12 recipients. The most common isolates were Gram-positive bacteria
      (73.9%) with domination of staphylococci (64.7%) and MRCNS strains (81.8%). Gram
      negative bacteria comprised 17.4% of positive cultures, whereas yeast-like fungi,
      8.7% with a predominance of Candida glabrata. CONCLUSION: Our study showed
      predominately Gram-positive bacteria in 73.9% of isolates. The increased
      proportion of multi-drug-resistant bacteria and fungi to antimicrobial agents may
      be due to the frequent use of these agents for prophylaxis of bacterial
      infections in patients.

PMID- 19857701
TI  - Impact of pancreas transplantation on the quality of life of diabetic renal
      transplant recipients.
AB  - Simultaneous pancreas and kidney transplantation (SPKT) is considered to be the
      best method of treatment for patients with chronic renal failure (CRF) resulting
      from insulin-dependent diabetes mellitus (IDDM). The aim of the study was to
      compare the quality of life (QOL) of patients with IDDM and CRF subjected to SPK
      or kidney transplantation alone (KTA). MATERIALS AND METHODS: We analyzed 21
      patients after SPKT with good function of both grafts. The results were compared
      with 17 patients with functioning kidney grafts. Minimal observation time was 6
      months. QOL was evaluated using Kidney Disease and Quality of Life Short Form
      (KDQOL-SF), which was sent to recipients by post. Results were presented as
      medians and interquartile ranges of calculated scored KDQOL-SF points. RESULTS:
      Observation time was 30 months (range, 6-85). Analyzed groups did not differ as
      regards patient age at transplantation or duration of diabetes and dialysis
      treatment before transplantation. After SPKT patients reported higher QOL
      compared with KTA as regards symptom/problem list, 90.91 (86.36-95.46) versus
      84.09 (75.00-90.91; P = .04), effects of kidney disease, 90.63 (84.38-93.75)
      versus 81.25 (68.75-82.14; P = .001); cognitive function, 93.33 (86.67-100.00)
      versus 80.00 (73.33-93.33; P = .03); overall health, 80.00 (70.00-90.00) versus
      50.00 (50.00-70.00; P = .001); physical functioning, 90.00 (75.00-100.00) versus
      80.00 (55.00-85.00; P = .03); and pain, 100.00 (90.00-100.00) versus 67.50 (45.00
      90.00; P = .005), respectively. CONCLUSION: SPKT had a positive impact on
      selected parameters of QOL among patients with IDDM and CRF compared to KTA.

PMID- 19857702
TI  - Risk stratification of patients with severe heart failure awaiting heart
      transplantation-prospective national registry POLKARD HF.
AB  - Most methods used in the risk assessment of heart transplant candidates do not
      include new biomarkers. AIMS: The aim of the study was to examine the value of
      NTproBNP and hsCRP and their combined use together with HFSS score in the risk
      assessment of patients with heart failure enlisted for heart transplantation.
      METHODS: Data of 658 patients enlisted for heart transplantation in all active
      transplantation centers were stored in a prospective registry. The composite end
      point-death or urgent transplantation was recorded during the follow-up. RESULTS:
      Death or urgent transplantation was recorded in 161 (24%) of pts. 102 (15%)
      patients died and 59 (9%) were transplanted urgently. Kaplan-Meier curves for
      risk of death or urgent transplantation where highly significant when pts were
      stratified by the quartiles of NT proBNP (P < .000001) or quartiles according to
      the hsCRP level on admission (P < .002). In the multivariate Cox proportional
      hazard model, the significance was observed for NTproBNP (P < .01) and HFSS (P <
      .02), and borderline significance for hsCRP (P = .057). When ROC analyses of the
      area under the curve (AUC) values were considered, AUC area was for HFSS - 0.645,
      for NTproBNP - 0.653 and for hsCRP - 0.566. When all those variables were
      included together in the model, the AUC value rose to 0.6943. Based on those
      results a weighted risk model with all three parameters was proposed. CONCLUSION:
      HFSS, NTproBNP and hsCRP levels are independent stratification variables of
      survival or need for urgent heart transplantation. Their predictive value is
      moderately increased when they are analyzed together.

PMID- 19857703
TI  - The influence of the recipient's body weight on the probability to obtain a heart
      transplant-POLKARD HF registry.
AB  - INTRODUCTION: The aim of the study was to analyze the influence of body weight of
      the adult heart recipient on the chance to obtain a transplant. METHODS: We
      analyzed the data from all 658 patients listed for heart transplantation.
      RESULTS: During the follow-up period, 325 (49%) of listed patients underwent
      transplantation with 102 (15%) succumbing before heart transplantation. The mean
      weight of transplanted patients was 73.7 +/- 13.7 kg and 81.2 +/- 15.4 kg for
      those not transplanted (P < .00001). Patients were divided according to body
      weight in two groups: light = below 80 kg (n = 360) or heavy > or = 80 kg or
      above (n = 297). On the transplant list, 111 heavy patients (37%) versus 213
      light patients (59%) underwent the procedure, a significant difference. The
      waiting time among light patients was 255 versus heavy patients of 395 days (P <
      .005). There was a similar number of deaths before transplantation among the
      light (n = 56 360 patients; 15.5%) versus the heavy group (49/297; 16%). Upon
      multivariate Cox mode analysis independent factors related to not receiving a
      heart transplant were greater weight, systolic blood pressure, pulmonary vascular
      resistance, Heart Failure Survival Score (HFSS) score and lower N-terminal pro
      brain natriuretic peptide (NTproBNP) levels. CONCLUSIONS: Among adult heart
      transplant candidates, the chance to receive a heart transplant significantly
      decreased when the recipient's weight exceeded 80 kg. Patients with a body weight
      more than 110 kg had a poor chance to receive a heart transplantation.

PMID- 19857704
TI  - Differences in antiapoptotic, proliferative activities and morphometry in dilated
      and ischemic cardiomyopathy: study of hearts explanted from transplant
      recipients.
AB  - BACKGROUND: Antiapoptotic as well as replacement and proliferative mechanisms
      take place in the myocardium in dilated cardiomyopathy (DCM) and ischemic heart
      disease (IHD). We sought to estimate antiapoptotic, proliferative and replacement
      activities in cardiomyopathies. MATERIALS: The study groups included seven hearts
      with DCM and eight with IHD, which had been explanted at the time of
      transplantation. The comparator group consisted of cases of myocardial
      hypertrophy and the control group, donor fragments. METHODS: Antiapoptotic and
      proliferative responses were determined immunohistochemically as Bcl-2 and Ki67
      expression by semiquantitative assessment of the intensity of staining. We also
      measured and statistically analyzed the integrative morphometric measurements of
      the fraction of fibrosis area, the nucleosarcoplasmic ratio, and cardiocyte
      diameter. RESULTS: No Bcl-2 expression was observed in the controls. The
      strongest reaction was seen in the DCM group, then in the IHD, and in the
      comparator group of myocardial hypertrophy. Proliferative activity was seen only
      in endocardial and interstitial fibroblasts in DCM and IHD cases. The cardiocyte
      diameter showed no statistical association between myocardial hypertrophy and
      IHD, or IHD and DCM, whereas the nucleosarcoplasmic ratios were significantly
      different from control groups for all comparisons. Myocardial fibrosis showed the
      highest values in DCM and IHD. Discriminant analysis showed the value of
      interstitial fibrosis and cardiocyte diameter to categorize the analyzed groups.
      CONCLUSIONS: Antiapoptotic Bcl-2 activity seemed to play an important role in
      cardiocyte preservation, while proliferative activity was resticted to
      interstitial connective tissue cells as a replacement process. Myocardial Bcl-2
      expression, the extent of myocardial fibrosis, and cardiocyte diameter may serve
      as additional diagnostic tools to differentiate cardiomyopathies.

PMID- 19857705
TI  - Pivotal karyometric measurements in different types of cardiomyopathic
      morphology: study of hearts explanted from transplant recipients.
AB  - BACKGROUND: Morphometric studies based on the measurement of cardiocyte nuclei
      have focused on progressive hypertrophy rather than shape, which is a deciding
      factor for the diagnosis of hypertrophy in myocardial diseases. The aim of this
      research was to demonstrate how the digital morphology of cardiocyte nuclei
      change correlated with the type of myocardial pathology. MATERIALS AND METHODS:
      The study groups encompassed 7 hearts with dilated cardiomyopathy (DCM) and 8
      hearts with ischemic heart disease (IHD) which were explanted. A comparative
      group consisting of myocardial hypertrophy was contrasted with a control group of
      donor heart fragments. Cardiocyte nuclei were evaluated morphometrically on
      histologic slides. We calculated the nuclear area, length, breadth, perimeter,
      roundness, elongation, fullness factors, and nuclear chromatin mean gray level.
      The results were subjected to discriminant analysis. RESULTS: All karyometric
      measurements analyzed by backward discriminant analysis showed only 2 powerful
      factors: nuclear breadth and chromatin mean gray level. The Mahalanobis distance
      showed the proximity of control and hypertrophy groups, whereas differences
      between IHD and DCM were nonsignificant. CONCLUSION: The lack of karyometric
      differences between IHD and DCM suggested a common morphologic response for long
      lasting progressive injury. The main morphologic differences were dependent on
      nuclear chromatin activity/stainability and nuclear breadth, suggesting darker
      and thinned nuclei in normal and adaptative stages and irregular brighter nuclei
      in cardiomyopathies.

PMID- 19857706
TI  - Different role of advanced glycation end products in pathology of transplanted
      heart in patients with or without diabetes mellitus type 2.
AB  - BACKGROUND: Aim of the study was to localize advanced glycation end products
      (AGEs) in late endomyocardial biopsies (EMBs) of orthotopic heart transplant
      (OHT) recipients with and without diabetes mellitus (DM) to correlate their
      presence with acute rejection episodes (ARE) and cardiac allograft vasculopathy
      (CAV). MATERIALS AND METHODS: Elective EMBs were performed at 3 years post-OHT in
      64 subjects, with DM (59 M/5 F), of overall mean age of 49 +/- 8 years and 24
      patients, without DM (21 M/3 F), of overall mean age of 42 +/- 10y. Localization
      of myocardial AGEs in paraffin sections was assessed immunochemically using mouse
      monoclonal anti-AGE antibodies (clone 6d12) on cardiomyocytes, stromal cells,
      connective tissue elements and capillaries. RESULTS: The occurrence of AGEs was
      similar in DM versus non-DM subjects: namely, cardiocytes 73% versus 63%, stroma
      33% versus 33%, connective tissue 13% versus 9%, and capillaries 31% versus 33%,
      respectively. Only in the DM group. The acute rejection episodes and mean EMB
      score significantly correlated with AGE presence in cardiomyocytes (r = 0.29/0.3;
      P = .02/.02; Spearman). There was no relation between AGE occurrence and CAV
      diagnosis among DM subjects, while the time free from angiographically confirmed
      CAV or a CAV-related event was significantly shorter among non-DM recipients
      without AGEs in capillaries and/or cardiocytes (P = .014/.017/.014/.03,
      respectively; log-rank). CONCLUSION: AGE occurrence in OHT recipients with DM was
      related to ARE, but not to CAV; in contrast, among non-DM patients it was not
      correlated with ARE, but their absence predicted CAV.

PMID- 19857707
TI  - Is there a difference between patients with peak oxygen consumption below 10
      ml/kg/min versus between 10 and 14 ml/kg/min? Does the "Grey Zone" really exist?
AB  - BACKGROUND: Cardiopulmonary exercise testing is an important component of
      evaluation when orthotopic heart transplantation (OHT) is considered for chronic
      heart failure (CHF) patients. However there is a question about the accuracy of
      interpretations of peak oxygen consumption (VO(2)max) used at present. MATERIALS
      AND METHODS: We analyzed 302 CHF patients stratified into 3 groups according to
      VO(2)max (mL/kg/min): group 1 = <10 (n = 37); group 2 = 10-14 (n = 121) and group
      3 = >14 (n = 144). We compared the mortality rate, the OHT rate, time to OHT,
      time to death and pulmonary function tests (PFT) among the groups using ANOVA
      Kruskal-Wallis tests for analysis in Statistica 7.1. RESULTS: No important
      differences were observed between groups 1 and 2 (P > .05), but first in
      comparison with group 3 (P < .05) in terms of mortality (48.6% vs 33.1% vs
      21.5%), number of OHT (24.3% vs 32.2% vs 14.6%), time to death (15.4 vs 16.6 vs
      34.4 months) or PFT results (forced expiratory volume in the first second forced
      vital capacity and peak expiratory flow, all as direct or as percent of normal
      values). In contrast, time to OHT (4.6 vs 6.9 vs 10.9 months) and percent of
      normal vital capacity (72% vs 81% vs 91%) differed significantly among all groups
      (P < .05). CONCLUSION: Patients with VO(2)max between 10 and 14 or <10 mL/kg/min
      are at similar risk of death.

PMID- 19857708
TI  - The influence of chronic heart failure on pulmonary function tests in patients
      undergoing orthotopic heart transplantation.
AB  - BACKGROUND: Chronic heart failure and airway obstruction produce overlapping
      syndromes. Existent criteria for the diagnosis and grading of airway obstruction
      based on spirometry results may be inadequate in the presence of coexistent
      cardiac failure. The cardiac component of pulmonary function tests (PFT) can be
      measured in patients undergoing orthotopic heart transplantation (OHT). MATERIALS
      AND METHODS: Before and 1 year after OHT between 2006 and 2008 PFT were performed
      in 29 patients according to existent guideline. Willcoxon matched pair tests were
      used for analysis in Statistica 7.1. The general group characteristic included
      age, gender, New York Heart Association class, CCS class, body mass index,
      present medications, blood and chemistry tests, as well as exercise tolerance
      tests, right heart catheterization, and echocardiography results. RESULTS: One
      year after OHT we observed significant improvements in forced expiratory volume
      in the first second (FEV1) and its percent of normal value (FEV1%) as well as
      forced vital capacity (FVC), FVC%, vital capacity (VC) and VC%: namely, 2.56 L
      versus 2.96 L; 82% versus 93%; 3.30 L versus 3.81 L; 85% versus 97%; 3.38 L
      versus 4.04 L and 85% versus 100% (all P < .01). FEV1 and FVC increments of: 0.39
      and 0.471 respectively, exceeded the cutoff point of 12% of predicted value
      established as the spirometry criterion for reversibility of obstruction.
      Elimination of heart failure by OHT did not significantly change the FEV1 to FVC
      ratio (FEV1%FVC). CONCLUSION: Chronic heart failure contributed to significant
      FEV1 reduction, which limits the usefulness of PFT for diagnosis and grading of
      airway obstruction. FEV1%FVC, the main diagnostic criterion of chronic
      obstructive lung disease, seems to be an index independent of concomittant heart
      function impairment.

PMID- 19857709
TI  - What else distinguishes cellular rejection grade 1A from 0? Annexin V and BCL in
      elective biopsies received from heart transplant recipients.
AB  - BACKGROUND: Despite morphologic differences of lymphocytes aggregation between
      nonrejection (0 on the International Society for Heart and Lung Transplantation
      [ISHLT] scale) and moderate focal cellular rejection (1a, ISHLT), genetic and
      clinical differences have not been shown in Cardiac Allograft Rejection Gene
      Observation (CARGO) studies. Therefore, we sought to compare the expression of
      selected antigens associated with apoptosis in heart transplant recipients in the
      context of grade 0 versus grade 1a cellular rejection episodes. We assessed the
      expression of annexin V, a nonspecific apoptosis marker, Bcl-2 as opposed to
      antiapoptotic activity of Bcl-xL and Bcl-xL/S. MATERIALS AND METHODS: We
      retrospectively examined 17 heart transplant patients (2 women and 15 men) of
      overall mean age of 46.2 +/- 13.9 years and body mass index of 25.7 +/- 3.2. Ten
      biopsies showed rejection grade 0 and the other 10, grade 1a on the ISHLT scale,
      comprising groups A and B, respectively. Endomyocardial biopsy specimens were
      processed using routine immunohistochemical methods. The expression of apoptotic
      molecules was assessed according to the IHC method: 0, the lack of expression; 1,
      trace; 2, distinct; and 3, strong. A correlation was analyzed between particular
      molecular expressions. RESULTS: We observed a significant increase in Bcl-2
      expression associated with rejection. The expression of other antigens did not
      show a significant tendency. No correlation was noted among group A, whereas in
      group B those were significant strong and negative correlations with Bcl-2 and
      Bcl-xL/S. CONCLUSION: Bcl-2 expression corresponded to the morphologic
      progression of graft rejection as opposed to Bcl-xL/S activity.

PMID- 19857710
TI  - Mixed cellular and humoral acute rejection in elective biopsies from heart
      transplant recipients.
AB  - OBJECTIVE: Acute cellular rejection in heart transplants is characterized by an
      active lymphocytic infiltration, whereas the humoral response shows complement
      deposits in myocardial tissue. Both reactions may produce hemodynamic compromise
      during the first months after orthotopic heart transplantation (OHT). The aim of
      this study was to estimate the coexistence of humoral rejection symptoms in the
      first posttransplant biopsy with mild/moderate cellular rejection as an
      additional prognostic factor. MATERIALS AND METHODS: The study group included 13
      biopsies obtained from 11 men and 2 women of overall mean age of 52.6 +/- 5.3
      years who displayed International Society for Heart and Lung Transplantation
      (ISHLT) mild/moderate rejection grades. The control group consisted of 11
      biopsies obtained from 8 men and 3 women of overall mean age of 54.8 +/- 3.6
      years with no signs of rejection. Complement deposits were determined
      immunohistochemically using anti-C4d antibodies (Quidel Corporation). RESULTS:
      None of the control cases showed a positive reaction, whereas 3 men in the study
      group of mean age of 56.1 +/- 5.8 years revealed regional positive anti-C4d
      expression with cellular infiltrates. This expression occurred in all myocardial
      components adjacent to lymphocytic infiltrations. The survival rates were
      comparable in both the pure cellular versus the mixed rejection groups. The
      relative rate of grade 3 rejection in the posttransplantation period was
      increased among patients with mixed types of rejection. CONCLUSIONS: The term
      "mixed acute rejection" should be applied to cases with coincidence of 2 forms of
      acute rejection. It seemed to be associated with more frequent grade 3 rejection
      processes upon long-term follow-up.

PMID- 19857711
TI  - Concentration of anti-7-ketocholesterol antibodies in patient sera after heart
      transplantation.
AB  - Oxidized low-density lipoproteins (ox-LDL) have been shown to be strongly
      atherogenic and immunogenic in experimental animals and in humans. Autoantibodies
      against ox-LDL and its various epitopes have been detected in sera and in
      atherosclerotic lesions. LDL oxidation may also lead to generation of oxidized
      derivatives of cholesterol (eg, 7-ketocholesterol [7-ketoCh]), which are
      characterized by high levels of cytotoxicity, muta- and carcinogenicity, as well
      as immunosuppressive effects and probable immunogenic properties. The aim of this
      study was to quantify autoantibodies to 7-ketoCh in sera from patients after
      orthotopic heart transplantation (OHT). IgG antibodies were measured in sera from
      81 patients after OHT and 73 healthy volunteers using and enzyme-linked
      immunosorbent assay (ELISA) method. For the antigen we used 7-ketoCh
      hemisuccinate conjugated to bovine serum albumin. Anti-7-ketoCh antibodies were
      detected in all examined sera. Their concentrations were significantly higher
      among OHT patients than the control group, namely, 109.0 +/- 109.7 vs 53.5 +/-
      20.0 U/mL (P < .005). Also, we observed a direct relationship between antibody
      concentration and time after OHT. Our results showed that the low molecular
      product of LDL oxidation, 7-ketoCh, was immunogenic possibly playing a role in
      the progression of atherosclerosis among OHT patients.

PMID- 19857712
TI  - Microvasculopathy observed in early or late endomyocardial biopsies is not
      related to angiographically confirmed transplanted heart coronary vasculopathy.
AB  - INTRODUCTION: The aim of the study was to examine the potential relation between
      microvasculopathy observed in endomyocardial biopsies (EMBs) and clinical
      coronary vasculopathy (CAV) after orthotopic heart transplantation (OHT).
      MATERIALS AND METHODS: We preformed a retrospective analysis involving 68 OHT
      patients in whom the procedure was performed before 1999. The CAV(+) group
      consisted of 37 subjects (35 males/2 females) of overall mean age of 45 +/- 11
      years. Ischemic cardiomyopathy was the diagnosis in 57% of the cohort that
      displayed CAV established by angioplasty, myocardial infarction, or CAV-related
      death. The control group contained 31 subjects (24 male/7 female) of overall mean
      age of 43 +/- 16 years. The pretransplant diagnosis was ischemic c-pathy in 39%.
      These subjects displayed negative coronary angiography at 10 years after OHT.
      Based upon studies early after OHT 55 subjects were divided based on the
      myocardial blush grade (MBG) upon coronary angiography performed between 4th and
      6th week after surgery: one cohort of six individuals showed decreased MBG (6
      males) of mean age 52 +/- 7 years. There was prior ischemic c-pathy in 50%. In
      contrast, 49 subjects showed a normal MBG (43 males/67 females) of overall mean
      age of 45 +/- 12 years. Ischemic c-pathy had been present in 39%.
      Microvasculopathy was defined as the presence of prominent endothelial cells,
      vacuolation of the endothelium, thickening of the basal membrane and/or muscle
      layer, the presence of lymphocytes in the arteriolar wall, periarteriolar
      fibrosis, or stenotic arteriolar lumenia in the 12- and 36 month EMB (CAV groups)
      or the 4-week EMB (MBG groups). RESULTS: Rejection grades were comparable in
      CAV(+) and CAV(-) groups, but decreased in normal MBG group. The only significant
      difference was observed in the occurrence of basal membrane thickening, which was
      present in 22% of subjects from the CAV(+) group and 3% of individuals from the
      CAV(-) group in the 12-month EMB. CONCLUSION: Microvasculopathy observed early or
      late after OHT was not related to angiographically confirmed CAV.

PMID- 19857713
TI  - The occurence of mood and anxiety disorders in heart transplant recipients.
AB  - Fortynine heart transplant recipients were evaluated during the first weeks after
      orthotopic heart transplantation. Using the ICD-10 (International Classification
      of Diseases-10th revision) criteria, we studied the incidence of anxiety
      disorders as well as 17 demographic and medical factors potentially influencing
      the probability of their occurrence. A smaller 36-person group was evaluated
      using standard psychopathologic scales for anxiety and mood disorders. Cox
      regression analysis was used to specify which of 11 demographic and medical
      factors influenced the time to occurrence of the first episode of a mental
      disorder. Anxiety episodes occurred in 25 patients, depressive episodes in 27,
      (hypo)manic in 3, and 12 manifested a slightly elevated mood. The risk of
      occurrence of anxiety and mood disorders was highest during the first 3 weeks
      after OHT. "False alarms," namely, calls to the clinic not ending up in
      transplantation, and coexisting illnesses were related to higher incidences and
      earlier appearance of anxiety and mood disorders. The risk of occurrence of an
      anxiety syndrome was greater among older patients. Anxiety syndromes were
      manifested earlier in patients who underwent transplantation due to ischemic
      cardiomyopathy than in patients with heart failure caused by other factors. A
      greater number of false alarms, of long-lasting hospitalizations, and of low mean
      cyclosporine levels were risk factors for depressive episodes.

PMID- 19857714
TI  - Cytomegalovirus infection does not accelerate microvasculopathy development in
      heart transplant recipients.
AB  - BACKGROUND: Clinical studies with intravascular ultrasound have suggested that
      even subclinical cytomegalovirus (CMV) infections increase intimal hyperplasia in
      transplanted heart coronary arteries after 1 year. The potential influence of CMV
      on microvasculopathy development is not known. The Aim of our study was to
      compare the occurrence of microvasulopathy in endomyocardial biopsies (EMBs) of
      heart transplant recipients with versus without CMV infection. MATERIALS AND
      METHODS: We performed a case-controlled, retrospective study of 58 subjects
      diagnosed with CMV infection by the presence of pp65 antigen. The 49 men and 91
      women of overall age 49 +/- 8 years showed ischemic cardiomyopathy in 52%. We
      matched a control cohort of 58 subjects without CMV disease. Microvasculopathy
      was assessed using 4-degree grading system developed by Hiemann et al for
      elective EMBs performed at 1 and 12 months after transplantation. RESULTS:
      Significant acute rejection episodes were observed among 22% versus 21% of 1
      month EMBs, and 3% versus 5% of 12-month EMBs for CMV(+) versus control group
      subjects respectively. The commonest microvasculopathy was nonstenotic thickening
      (grade B) 60% versus 59% (35 versus 34 patients) among 1-month EMBs; and 50%
      versus 60% (29 vs 35 patients) among 12-month EMBs, respectively. Progression of
      microvasculopathy score between 1- and 12-month EMB was observed in 40% versus
      41% of subjects, and regression occurred in 22% versus 21%, respectively. None of
      differences was significant. CONCLUSION: Our data do not support the thesis that
      CMV infection promotes microvasculopathy development among heart transplant
      recipients.

PMID- 19857715
TI  - Frequency of Pseudomonas aeruginosa colonizations/infections in lung transplant
      recipients.
AB  - BACKGROUND: Lower respiratory tract infections remain a leading cause of
      morbidity and mortality after solid organ transplantation. The particularly
      increased susceptibility to infection is an especial problem in the early
      posttransplant period at the initial stage of immunosuppression, owing to direct
      contact with the hospital environment by mechanical ventilation, biopsies,
      injections, bronchoscopy, and bladder and vessel catheterizations exacerbated by
      the impaired clearance mechanisms after denervation of the transplanted lung.
      Airway colonization with Pseudomonas aeruginosa is common in lung transplant (LT)
      recipients. Therefore, we performed a retrospective analysis to address the
      frequency of P aeruginosa infections in our Center. MATERIALS AND METHODS: From
      January 2004 to December 2008, we performed 33 LT, including 4 heart-lung, 6
      double, and 23 single lung transplantations. Respiratory samples were the main
      diagnostic material undergoing routine microbiological methods. RESULTS: P
      aeruginosa was isolated from 13 patients (39.4% of all 33 LT). In 10 cases
      (30.3%), we observed airway colonization together with lower respiratory tract
      infections. From 2005 to 2008, P aeruginosa was diagnosed in about 50% of LT
      patients each year: in 2005, 33.3%; 2006, 57.1%; 2007, 42.9%; and 2008, 40%.
      CONCLUSION: LT recipients in our center are at high risk for pseudomonal airway
      colonisation and lower respiratory tract infection that may have a significant
      impact on posttransplant follow-up.

PMID- 19857716
TI  - Procalcitonin serum concentration during Pneumocystis jiroveci colonization or
      Pseudomonas aeruginosa infection/colonization in lung transplant recipients.
AB  - BACKGROUND: Allograft infection after lung transplantation (OLT) has a
      significant impact on outcomes and represents a diagnostic challenge.
      Pneumocystis jirovecii causes an opportunistic infection, life-threatening
      pneumonia among immunocompromised patients. Airway colonization with Pseudomonas
      aeruginosa is common in lung transplant recipients. The aim of the study was to
      evaluate procalcitonin (PCT) serum concentrations during P jiroveci and P
      aeruginosa colonization/infections in lung transplant recipients. MATERIALS AND
      METHODS: Fifteen OLT patients were retrospectively enrolled into the study (10
      men and 5 women) of overall mean age of 41.4 +/- 14.6 years. In seven patients, P
      jiroveci cysts were diagnosed (group J) and in 13 patients, we isolated P
      aeruginosa (group A). In respiratory samples, P jiroveci was detected using an
      indirect immunofluorescence method, and P aeruginosa was isolated using routine
      microbiologic methods. PCT was measured using immunoluminescence assay. RESULTS:
      The average PCT value in group A was 0.30 +/- 0.21 and in group J, 0.88 +/- 0.43,
      a difference that was not significant. In group A, 3 patients (23.1%) has PCT
      values indicating moderate infection risk (PCT > 0.5) and one patient (7.7%), a
      high infection risk (PCT > 2.0 and <10). In group J, three patients (42.9%) has
      PCT values indicating moderate and one patient (14.3%), high infection risk.
      CONCLUSIONS: Bronchial tree colonization with P jiroveci as well as P aeruginosa
      colonization can be associated with increased PCT suggesting a general, systemic
      response in addition to local colonization.

PMID- 19857717
TI  - Anemia is a predictor of outcome in heart transplant recipients.
AB  - BACKGROUND: Cardiovascular disease and kidney disease share similar
      characteristics. It has been recently recognized that many patients with
      cardiovascular disease have anemia, which often is associated with kidney
      dysfunction. Even the term "cardiorenal anemia syndrome" was endorsed to stress
      the dangerous association. OBJECTIVE: To assess the prevalence of anemia in
      relation to chronic kidney disease in 160 patients after orthotopic heart
      transplantation. RESULTS: According to the World Health Organization definition
      of anemia (hemoglobin concentration <13 g/dL in males and <12 g/dL in females),
      41% of our patients had anemia. Patients with anemia exhibited a significantly
      lower mean (SD) glomerular filtration rate (GFR) using the Modification of Diet
      in Renal Disease formula vs the Cockcroft-Gault formula: 44.46 (26.84) mL/min vs
      62.70 (24.15) mL/min and 48.93 (27.80) mL/min vs 72.11 (29.76) mL/min,
      respectively (P < .001). In addition, they demonstrated lower creatinine
      clearance, red blood cell count, hemoglobin concentration, and ejection fraction
      and significantly higher creatinine and N-terminal probrain natriuretic peptide
      concentrations. Presence of anemia was associated with time since
      transplantation, GFR, creatinine clearance, N-terminal probrain natriuretic
      peptide and cholesterol concentrations, and ejection fraction. At multiple
      regression analysis, the only predictor of anemia was kidney function (GFR or
      creatinine clearance), which accounts for 22% of the variation. Type of
      immunosuppression regimen (calcineurin inhibitors vs mammalian target of
      rapamycin) did not seem to affect prevalence of anemia in the study population.
      CONCLUSIONS: The prevalence of anemia is relatively high in heart allograft
      recipients and is not adequately treated. In patients with cardiovascular
      disease, GFR should be estimated because renal dysfunction and subsequent anemia
      are important risk factors for cardiovascular morbidity and mortality. Chronic
      heart failure is also more common in patients with anemia.

PMID- 19857718
TI  - Urinary iodine concentrations should be monitored to diagnose some thyroid gland
      diseases in heart transplant recipients.
AB  - BACKGROUND: According to the World Health Organization, iodine excreted in urine
      is a measure of its supply. According to the International Council for Control of
      Iodine Deficiency Disorders (ICCIDD), the urinary iodine (UI) should be >100
      microg I per 1 liter of urine. Severe deficiency (SID) is diagnosed when UI is
      <50 microg/L and a moderate deficiency (MID) when UI is <100 microg/L. MATERIALS
      AND METHODS: UI analysis among 32 heart transplant recipients (26 men and 6
      women); of overall mean age of 50.4 +/- 12.6 years was performed using the
      modified Program Against Micronutrient Malnutrition method, a spectrophotometric
      measurement based on the Sandell-Kolthoff reaction. Results were compared with
      those of thyroid stimulating hormone (TSH; microIU/mL), of free tri-iodothyronine
      (FT3; pg/mL), and thyroxine (FT4; ng/dL). RESULTS: The average UI among the whole
      group was 126.4 +/- 109.6 microg/L. SID occurred in 12 patients (37.5%) and MID
      in 4 (12.5%); namely, mean UI of 17.0 +/- 9.6 and 79.5 +/- 5.6, respectively. In
      the other 16 patients (50%), the average UI was high, namely, 220.1 +/- 72.1
      IU/mL. TSH, FT3, and FT4 in the whole group were within normal ranges. However,
      FT4 values significantly differed when SID and MID patients were compared with
      those displaying the recommended UI: 0.8 +/- 0.2 and 0.9 +/- 0.1 versus 1.1 +/-
      0.2 respectively (P < .05). We noted decreased values of TSH in 5 patients
      (15.6%) and of FT3 or FT4 in 6 subjects (18.8%). CONCLUSION: There exists
      significant iodine deficiency among heart transplant recipients. Measurements of
      urinary iodine together with thyroid gland hormones may be essential to prevent
      thyroid gland disturbances in these patients.

PMID- 19857719
TI  - Predictors of kidney dysfunction in heart transplant recipients.
AB  - Cardiovascular disease and kidney disease seem to be lethally synergistic, both
      approaching the level of epidemics. Patients with cardiovascular disease often
      have impaired kidney function; on the other hand, cardiovascular disease is the
      single best predictor of mortality among patients with chronic kidney disease.
      The risk in a patient with moderately impaired renal function is comparable in
      magnitude to that of a patient with diabetes mellitus. The aim of this study was
      to assess risk factors for kidney dysfunction among 162 prevalent heart
      transplant (OHT) recipients (127 males and 22 females). Stages of chronic kidney
      disease were defined according to Kidney Disease Outcomes Quality Initiative
      guidelines using the estimated glomerular filtration rate (GFR). Mean serum
      creatinine in this population was 1.70 +/- 1.08 mg/dL (range, 0.54-9.34). The
      mean age was 54 +/- 14 years and the average time after transplantation was 106
      +/- 52 months (range, 10-210). Mean GFR was 62.92 +/- 31.04 mL/min (Cockcroft
      Gault formula), 55.38 +/- 26.74 mL/min (MDRD), and 62.62 +/- 35.61 mL/min
      (creatinine clearance). Estimated GFR, creatinine clearance, and serum creatinine
      correlated upon univariate analysis with hemoglobin, red blood cell count, age,
      time after transplantation, ejection fraction, N-terminal prohormone brain
      natriuretic peptide, and use of calcineurin inhibitors. Upon multiple regression
      analysis predictors of kidney function (GFR) were age (beta value, -0.47; P <
      .001), time after transplantation (beta value, -0.22; P = .03), and hemoglobin
      (beta value, 0.31; P = .03), explaining 51% of the variation among GFR values in
      this group. When GFR was substituted with creatinine clearance, the results were
      similar. Among heart transplant recipients, kidney function was predominantly
      dependent on age and time after transplantation (both nonmodifiable causes), as
      well as anemia (which may be modified).

PMID- 19857720
TI  - Prevalence of chronic kidney disease is extremely high in heart transplant
      recipients.
AB  - Patients with cardiovascular disease often have renal dysfunction from
      concomitant diabetes mellitus, hypertension, or congestive heart failure.
      Glomerular filtration rate (GFR) less than 60 mL/min is predictive of premature
      death due to cardiovascular disease. The objective of the present study was to
      assess the prevalence of kidney dysfunction in 162 heart transplant recipients
      using estimated GFR according to the Cockcroft-Gault and the simplified
      Modification of Diet in Renal Disease (MDRD) formulas or creatinine clearance (24
      hour urine collection). Normal serum creatinine concentrations were noted in 46%
      of patients. Mean (SD) GFR was 62.92 (31.04) mL/min using the Cockcroft-Gault
      formula, 55.38 (26.74) mL/min using the MDRD formula, and 62.62 (35.61) mL/min
      according to creatinine clearance. Using the Cockcroft-Gault formula, a diagnosis
      of stage 2 chronic kidney disease (CKD) (GFR 60-89 mL/min) was made in 92
      patients (56.8%), stage 3 (GFR 30-59 mL/min) in 62 patients (38.3%), and stage 4
      (GFR 15-29 mL/min) in 14 patients (8.6%). Using the MDRD formula, stage 2 CKD was
      present in 52 patients (28.5%), stage 3 in 77 (51.1%), and stage 4 in 28 (17.3%).
      According to creatinine clearance, stage 2 CKD was noted in 10 patients (6.2%),
      stage 3 in 114 (73.3%), and stage 4 in 21 (13.0%). We conclude that the
      prevalence of CKD is extremely high in heart transplant recipients. Evaluation of
      renal function is important to select the appropriate technique to reduce
      cardiovascular risk. A multidisciplinary approach in heart transplant recipients
      should include a nephrologist.

PMID- 19857721
TI  - Plasma neutrophil gelatinase-associated lipocalin (NGAL) correlations with
      cystatin C, serum creatinine, and glomerular filtration rate in patients after
      heart and lung transplantation.
AB  - OBJECTIVE: Kidney injury represents a major clinical problem in orthotopic heart
      transplant (OHT) patients which seriously increases the mortality rate. The aim
      of this work was to evaluate the utility of a new kidney damage marker-neutrophil
      gelatinase-associated lipocalin (NGAL)-and its correlations with cystatin C,
      creatinine, and glomerular filtration rate (GFR) among patients after heart or
      lung transplantation. MATERIALS AND METHODS: We examined serum samples from 71
      patients after heart transplantation, 7 patients after lung transplantation, and
      20 healthy controls to measure serum NGAL using an enzyme-linked immunosorbent
      assay (ELISA) method; cystatin C using latex immunonephelometry; and creatinine
      using the alkaline-picrate method. RESULTS: Serum NGAL levels were significantly
      elevated among transplant patients, but did not significantly correlate with
      cystatin C in the transplant group (R = .13; P = .11) or in the control group (R
      = .26; P = .26), or GFR in the transplant group (R = -.09; P = .25) or in the
      control cohort (R = .22; P = .36). In the transplant group, serum NGAL positively
      correlated with serum creatinine (R = .27; P = .001). CONCLUSIONS: Plasma NGAL
      was not a specific biomarker for monitoring chronic renal disorders. We did not
      exclude other pathologies that might contribute to increased serum NGAL levels.

PMID- 19857722
TI  - Palonosetron in prevention of nausea and vomiting after highly emetogenic
      chemotherapy before haematopoietic stem cell transplantation-single center
      experience.
AB  - OBJECTIVE: A clinical study of palonosetron was performed to evaluate its
      efficacy in preventing both acute and delayed emesis after high-dose chemotherapy
      (HDC) before hematopoietic stem cell transplantation (HSCT) using a historical
      control group of patients treated with ondansetron as the comparative drug.
      METHODS: Among the 46 evaluated patients 20 with lymphoma received BEAM as the
      conditioning regimen; 16 has relapsed germ cell tumors treated with CARBOPEC; and
      10 with acute myeloid leukemia received BuCY. Increasing severity of nausea was
      evaluated according to the following 4-grade scale: none (no nausea); mild
      (slight nausea but no disruption to daily activities); moderate (nausea and some
      disruption to daily activities); and severe (extreme nausea and severe disruption
      to daily activities). The emetic response rate was evaluated using the criteria:
      complete (no emetic episode); major (1-2 episodes); minor (3-5 episodes); and
      failure (>5 episodes). The response rate of the study drugs was evaluated by the
      following 4-grade scale based on the condition of nausea and vomiting: highly
      effective, moderately effective, slightly effective, and not effective. RESULTS:
      Patients treated with palonosetron showed significantly greater response rates
      than those receiving ondansetron during the both the acute and the delayed
      phases: highly and moderately effective: acute phase 15% versus 5% CARBOPEC; 70%
      versus 35% BEAM and 32% versus 20% BuCY; delayed phase: 60% versus 30% BuCY; 100%
      versus 50% BEAM and 25% versus 10% CARBOPEC. CONCLUSIONS: Single-dose
      palonosetron was more effective than ondansetron treatment to prevent acute and
      delayed nausea and vomiting following HDC before HSCT.

PMID- 19857724
TI  - Molecular epidemiology of vancomycin-resistant Enterococcus faecalis among
      patients of transplantology wards.
AB  - OBJECTIVE: Vancomycin-resistant enterococci (VRE) require epidemiological
      monitoring especially in transplantation wards. The aim of our work was to
      perform a molecular analysis of vancomycin-resistant Enterococcus faecalis
      (VREfl) strains among solid organ recipients during various years. MATERIALS AND
      METHODS: Strains were examined for the presence of different genes determining
      vancomycin resistance: vanA, vanB, vanD, or vanG by polymerase chain reaction
      (PCR). Restriction fragment length polymorphism (RFLP)-pulsed field gel
      electrophoresis (PFGE) was performed on bacterial DNA digested with SmaI enzyme.
      RESULTS: From 2003 to 2006, we isolated 12 strains of VREfl from 8 patients (2
      liver and 6 kidney transplantations). All strains harbored the vanA gene. Among
      the strains, 5 displayed patterns similar to each other, despite being isolated
      from different patients, and were susceptible to ampicillin with high resistance
      to aminoglycosides. CONCLUSIONS: These results suggested that a single strain of
      VREfl was present for 3 years in closely related hospital wards, but it
      disappeared in the following years.

PMID- 19857723
TI  - CTX-M and TEM as predominant types of extended spectrum beta-lactamases among
      Serratia marcescens isolated from solid organ recipients.
AB  - BACKGROUND: Serratia marcescens is an important pathogen in hospital infections
      since organisms resistant to multiple antimicrobials pose a special threat
      particularly among transplant patients. The aim of this work was to assess the
      number of strains producing beta-lactamases with extended spectrum (ESBL) among
      S. marcescens isolated from our patients. MATERIALS AND METHODS: We investigated
      S. marcescens isolated from 2005 to 2008 for ESBL. The phenotype methods were
      applied and additionally we chose strains for polymerase chain reactions using
      primers for the most popular types of ESBL. RESULTS: Over the investigated time,
      257 patients were infected with S. marcescens with 188 (73%) displaying an ESBL
      positive phenotype. A Molecular analysis showed that most of them produced both
      CTX-M and TEM beta-lactamases. In the last year, the percentage of ESBL-producing
      strains decreased, but also in the last year, we isolated S. marcescens resistant
      to carbapenems from three patients. CONCLUSIONS: The CTX-M type of ESBL
      predominated among ESBLs produced by strains of S. marcescens. The appearance of
      strains resistant to carbapenems is alarming.

PMID- 19857726
TI  - Molecular epidemiology of vancomycin-resistant Enterococcus faecium infecting
      recipients of solid organs in the transplant surgery ward in 2005 and 2006.
AB  - BACKGROUND: The aim of the investigations was to compare the vancomycin-resistant
      Enterococcus faecium (VREfm) strains obtained from our patients. MATERIALS AND
      METHODS: Strains were compared using restriction fragment length polymorphism
      pulsed field gel electrophoresis (RFLP-PFGE) of bacterial DNA. RESULTS: VREfm
      infected 26 liver recipients, 22 kidney recipients, and 9 other surgery or
      nephrology patients. Only five strains possessed the vanB determinant. The PFGE
      analysis revealed two large and several small groups of related strains.
      CONCLUSIONS: The PFGE analysis enabled the investigation of VRE epidemiology
      among patients after transplantation. Strains with similar patterns most probably
      originated from one source and clearly suggested an outbreak.

PMID- 19857725
TI  - Resistance to carbapenems among Pseudomonas aeruginosa isolated from patients of
      transplant wards.
AB  - BACKGROUND: The aim of the study was to estimate the carbapenems resistance and
      occurrence of metallo-beta-lactamase (MBL) production among Pseudomonas
      aeruginosa isolated from patients during the last 2 years. MATERIALS AND METHODS:
      We investigated all P aeruginosa strains derived from Transplantation Institute
      patients, hospitalized from January 2007 to December 2008. E-tests as well as the
      three-discs method with imipenem, ceftazidime were used for MBL detection. For
      the chosen strains, a PCR method was applied for detection of genes determining
      VIM, IMP, and SMP. RESULTS: Among 311 isolated strains from 228 patients only one
      strain was used for each patient. We showed increased resistance to carbapenems
      among P aeruginosa in 2008 compared with 2007: from 14% to 22%. About 60% of
      resistant strains displayed the MBL phenotype. Upon PCR analysis, the VIM-type
      metallo-beta-lactamase was detected in 70% of them. CONCLUSIONS: Despite similar
      numbers of P aeruginosa-infected patients in 2007 and 2008, the percentage of MBL
      producing strains increased from 7% to 15%. Most MBLs belonged to the VIM type.

PMID- 19857727
TI  - Algorithm of clinical protocol lowering the risk of systemic Mycosis infections
      in allografts recipients.
AB  - The aim of the study was to describe a diagnostic protocol to lower the risk of a
      mycotic invasive infection among allotransplant recipients and to suggest the use
      of preoperative prophylaxis and/or empiric therapy. We chose a group of 268
      allograft recipients with transient or constant yeast colonization or confirmed
      yeast infection. Among 7744 clinical samples, 475 were positive for fungi. We
      used conventional fungal laboratory diagnosis, enzymatic activity tests,
      serologic tests, molecular diagnosis of samples from sterile body sites, and
      histopathologic examinations. The following clinical samples were examined: blood
      samples; swabs from mouth lesions, throat, and rectum; and sputum, urine, and
      fecal samples from kidney transplant recipients and simultaneous pancreas-kidney
      transplantation recipients who are highly predisposed to mycotic infections. We
      established microbiologic criteria of a systemic mycosis and principles to
      distinguish colonization from infection.

PMID- 19857728
TI  - The influence of tissue fluid/lymph cytokines and growth factors on human
      keratinocyte proliferation and differentiation.
AB  - Cultured keratinocytes (KC) are needed for transplantation to the surface of
      large burn wounds and ulcers. They can be cultured in artificial media. However,
      the yield is always limited, viability is low, and proliferation and migration
      after grafting are slow. The question arose whether tissue fluid/lymph, which is
      a natural humoral environment for epidermal and dermal cells, contains
      cytokine(s) specifically regulating KC proliferation and could be used to culture
      large numbers of cells for transplantation. Culturing of skin keratinocytes in
      dermal tissue fluid/lymph containing keratinocyte growth factor, interleukin
      1beta, interleukin-6, tumor necrosis factor-alpha, and transforming growth factor
      beta revealed its strong stimulatory effect on the expression of p63 stem cell
      marker and proliferation but not differentiation of KC. Neutralizing these
      cytokines with antibodies resulted in decreased percentages of mitotic figures.
      None of the individual cytokines showed a dominant effect on proliferation. This
      observation suggests that either there may be other (so far undetected) specific
      cytokines or that the proliferation and differentiation of keratinocytes is an
      effect of the combined action of all investigated cytokines.

PMID- 19857729
TI  - Preface: 8th annual meeting of the French-Speaking Society of Transplantation.

PMID- 19857730
TI  - Organ donation: a portrait of family refusal in Quebec.
AB  - Many studies from around the world have reported different reasons why families
      refuse organ donation. In Quebec, however, there are no known data on the
      subject. To enable us to better communicate with families, a research project was
      conducted from January to December 2007 in hospital centers with personnel who
      specialize in supporting families. Our objective was to identify the reasons why
      Quebecers refuse a request for organ donation. The findings demonstrate that
      knowing the express wishes of the deceased person about organ donation and end-of
      life treatment influences the family. When these wishes are not known, the
      partners of older donors refuse in greater numbers, primarily for familial or
      circumstantial reasons. Refusal based on religion or ethnicity is rare. Some
      families approached before neurologic death is diagnosed do not wish to wait
      until all the criteria for neurologic death are met.

PMID- 19857731
TI  - Pulmonary recruitment protocol for organ donors: a new strategy to improve the
      rate of lung utilization.
AB  - Because lung transplantation is the only effective therapy for terminal
      respiratory failure, the demand for donor lungs has increased steadily. However,
      the number of donors has remained fairly constant over the years, which results
      in an increasing duration of waiting for lung transplantation. To overcome the
      lack of organs, various strategies have been developed by transplant centers
      including use of marginal donors. To increase the lung utilization rate in
      multiorgan donors, we implemented a simple lung recruitment protocol involving a
      brief period of controlled sustained inflation. In 2005, the lung utilization
      rate in the transplant program at our institution was only 20% in multiorgan
      donors. With the lung recruitment protocol, the rate of lung utilization for
      transplantation increased to 33%, in 2006, 24% in 2007, and 24% in 2008.
      Following the lung recruitment protocol, the arterial oxygen tension/fraction of
      inspired oxygen ratio increased to greater than 15% in more than 40% of donors.
      We were able to improve gas exchange sufficiently that as many as two-thirds of
      the lungs were suitable for transplantation. During the protocol, no
      complications were reported, and no patient became hemodynamically unstable,
      precluding organ procurement. We believe that optimization of multiorgan donor
      management with simple interventions may improve oxygenation, reducing the number
      of inadequate donor lungs and increasing the overall donor pool and organ
      availability.

PMID- 19857732
TI  - Lengthy cold ischemia time is a modifiable risk factor associated with low
      glomerular filtration rates in expanded criteria donor kidney transplant
      recipients.
AB  - The proportion of expanded criteria donor (ECD) kidneys transplanted in North
      America is steadily increasing. By definition, graft survival is shorter for ECD
      than standard criteria donor (SCD) kidneys. Seeking to identify factors
      associated with low posttransplant glomerular filtration rates (GFR), we
      retrospectively reviewed data on 390 consecutive patients transplanted in our
      center from January 1999 to December 2006 including 78% SCD and 22% ECD by UNOS
      criteria. We analyzed donor and patient characteristics, HLA mismatches, cold
      ischemia time (CIT) and delayed graft function (DGF). Pulsatile perfusion was not
      used. The average CIT was 14.6 hours for all SCD and ECD cases. All patients
      received thymoglobulin, a calcineurin inhibitor, mycophenolate mofetil, and
      steroids. The only factor associated with low estimated GFR in the entire ECD
      cohort was CIT. The average CIT for the ECD group was 18.3 hours, whereas it was
      only 13.6 hours for those in the SCD group (P < .001). We observed that at 6
      months posttransplant, those in the ECD group are 2.2 times more likely (odds
      ratio, 2.23; 95% confidence interval, 1.065-4.654; P = .033) to have an estimated
      GFR < or =50 mL/min/1.73 m(2) compared with those in the SCD group for CIT up to
      18 hours. The higher odds ratio for low estimated GFR was sustained at 3 years
      posttransplant. In our center, a lengthy CIT was an early risk factor associated
      with impaired renal function. We concluded that all efforts should be made to
      reduce CIT.

PMID- 19857733
TI  - A new preservation solution (SCOT 15) Improves the islet isolation process from
      pancreata of non-heart-beating donors: a Murine model.
AB  - INTRODUCTION: Due to the organ shortage, there is increased use of organs
      harvested from non-heart-beating donors (NHBD). These organs have been subjected
      to a period of warm ischemia that is most deleterious to functional recovery. We
      have designed a new preservation solution, "Solution de Conservation des Organes
      et des Tissus" (SCOT 15; Macopharma, Tourcoing, France) which contains an
      extracellular ionic composition including PEG 20 kD (15 g/L) as a colloid.
      METHODS: Our objective was to compare SCOT 15 with University of Wisconsin (UW)
      solution or islet culture medium CMRL 1066 + 1% of Bovine Serum Albumin (BSA), as
      the working and preservation solution for islet isolation from pancreata
      subjected to warm ischemia using a murine model. RESULTS: Warm ischemia decreased
      the islet yield and cellular viability regardless of the preservation solution.
      Either when the pancreas was or was not subjected to warm ischemia, the best
      islet yield was obtained with SCOT 15 (P < .05 vs UW or CMRL 1066). The same
      results were observed for islet viability as assessed using the 3,(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test; namely, better
      viability with SCOT 15 as compared with UW or CMRL 1066 (P < .01). CONCLUSION: In
      a murine model SCOT 15 was a better preservation solution for islet isolation
      than UW solution or culture medium (CMRL 1066).

PMID- 19857734
TI  - Evaluation of pulsatile perfusion machine RM3 for kidney preservation in a swine
      model of renal autotransplantation.
AB  - AIM: Transplantations of kidneys from non-heart-beating donors (NHBD) are
      intended to increase the donor pool by 20% to 30%. Nevertheless the rate of
      primary nonfunction and delayed graft function is generally higher among this
      group of donors. The goal of this study was to assess whether kidney preservation
      by a pulsatile perfusion machine was able to limit the renal lesions due to
      ischemia reperfusion injuries as compared with static incubation. We have used a
      model of an autotransplanted kidney exposed to controlled warm ischemia in the
      pig to mimic the clinical conditions of NHBD. MATERIAL AND METHODS: Left kidneys
      from 11 large white pigs aged 4 weeks were harvested after vascular clamping of
      the renal vessels for 1 hour. Kidneys were preserved for 22 hours. Two groups
      were studied: the MPS static group (static incubation with Belzer MPS; n = 6)
      versus the MPS RM group (renal perfusion with Belzer MPS; n = 5). Kidneys were
      then autotransplanted into pigs after a right nephrectomy. The primary end point
      was animal survival rate at 1 month. Secondary endpoints were evolution of the
      plasma creatinine values, proteinuria, tubular sodium reabsorption, and
      histological features at 1 month. RESULTS: For all biological parameters, the
      differences between the perfusion and the static incubation groups were
      significant, except creatinine, with favorable effects for the perfusion machine
      group. The histological data at 1 month showed recovery of the normal kidney
      architecture in the MPS RM group. CONCLUSION: In our pig experimental model that
      reproduced the clinical conditions of a NHBD, we demonstrated better kidney
      preservation when the pulsatile perfusion machine was used as compared with
      static conservation.

PMID- 19857735
TI  - Kidney transplantation in HIV-positive patients: report of our first 7 cases.
AB  - INTRODUCTION: Infection with human immunodeficiency virus (HIV) is associated
      with end-stage renal disease (ESRD). Although many teams initially were reluctant
      to offer kidney transplantation as a therapeutic option in HIV-positive patients
      with ESRD, new drug regimens introduced in the late 1990s have dramatically
      improved the life expectancy in these patients. OBJECTIVE: To report the results
      of the first 7 kidney transplantation procedures in HIV-positive patients at our
      institution. PATIENTS AND METHODS: Patients were selected to minimize the risks
      of HIV disease progression, opportunistic infections, and tumors. Protease
      inhibitor therapies were suspended because of possible interaction with
      immunosuppression drugs. The induction regimen did not include lymphocyte
      depleting drugs. After undergoing transplantation, patients were monitored by the
      transplantation and infectious disease teams. RESULTS: To date, all patients are
      alive with functioning grafts. We did not observe any episodes of acute
      rejection, and there were few adverse events. Drug tolerance was good for both
      immunosuppression and antiretroviral therapies. CONCLUSION: Kidney
      transplantation in HIV-positive patients with ESRD is warranted. Provided that
      patients are carefully selected, good results can be achieved with few adverse
      events, episodes of acute rejection, and drug interactions. Posttransplantation,
      these patients must be closely monitored by both the transplantation and
      infectious diseases teams to ensure optimal management.

PMID- 19857736
TI  - Genetic polymorphisms of immunoregulatory proteins in acute renal allograft
      rejection.
AB  - CTLA-4 and CD28 are T lymphocyte receptors involved in the regulation of T-cell
      activation. Allograft rejection is an alloimune response which is strongly
      dependent on T-cell proliferation. Thus, we examined the relationship between
      CTLA-4 and CD28 gene polymorphisms and renal transplant outcomes. We genotyped
      141 renal recipients and 229 healthy controls using PCR-SSP methods for the (
      318) C/T polymorphism in the promoter region of the CTLA-4 gene and IVS3 (+17)
      T/C on intron 3 of the CD28 gene, and by PCR-RFLP method for exon 1 (+49) A/G and
      CT60 G/A within the 3'-untranslated region (UTR) of the CTLA-4 gene. Patients
      were classified into two groups: Group I included 23 HLA-identical haplotype
      allograft recipients and group II, 118 recipients with one or more mismatches in
      HLA haplotypes. Thirty-six patients developed at least one acute rejection
      episode (ARE). No significant differences were observed between the genotypes or
      the allele distribution between ARE and non-ARE patients. However, in group I,
      (+49) A and CT60 (G) allele frequencies were lower in patients with ARE than
      those without ARE (0.100 and 0.400 vs 0.361 and 0.722 respectively). However, the
      difference was not significant. Our study suggested that these alleles may confer
      protection against renal allograft loss.

PMID- 19857737
TI  - Conversion from calcineurin inhibitors to sirolimus in kidney transplant
      recipients: a retrospective cohort study.
AB  - BACKGROUND: Replacing a calcineurin inhibitor (CNI) with sirolimus (SRL) may
      preserve kidney graft function. However, at the present time, only short follow
      up after conversion is available. The aim of this study was to assess whether
      conversion from a CNI-based to an SRL-based maintenance regimen was safe and
      effective. MATERIALS AND METHODS: We performed a retrospective cohort study among
      kidney graft patients whose CNI was withdrawn to be replaced by SRL. Two-tailed
      paired t tests were used to compare glomerular filtration rates (GFRs) and
      proteinuria levels before and up to 2 years after conversion. We used linear
      regression to determine the factors associated with changes in renal function
      after conversion. RESULTS: The 193 study subjects had a mean GFR at conversion of
      41 +/- 16 mL/min/1.73 m(2) a median proteinuria level of 0 g/L (interquartile
      range = 0-0.15). After conversion, the GFR was stable: at 1 year, the change was 
      0.34 mL/min/1.73 m(2) (95% confidence interval [CI] = -2.71, 2.03) and at 2
      years, -0.96 mL/min/1.73 m(2) (95% CI = 4.26, 2.34). There was a small but
      significant increase in dipstick proteinuria at 1 year of +0.5 g/L, (95% CI =
      0.20, 0.75). On multivariate analysis, proteinuria > or = 1 g/L at the time of
      conversion was the only predictor of deteriorating GFR at 1 year (beta: -7.91
      mL/min/1.73 m(2); 95% CI = -14.10, -1.70). SRL had to be discontinued in 31% of
      patients. CONCLUSION: Conversion from CNI to SRL resulted in stable graft
      function at 2 years and in a slight increase in proteinuria. Despite the
      relatively high reconversion rate, this strategy offers a reasonable alternative
      to CNIs for most patients.

PMID- 19857738
TI  - Chronic transplant vasculopathy microenvironment present in the renal allograft
      reprograms macrophage phenotype.
AB  - Macrophages and monocytes are important in chronic allograft dysfunction. Chronic
      transplant vasculopathy is an important cause of chronic renal allograft
      dysfunction. It is characterized by the presence of apoptotic endothelial cells,
      which generate an apocrine loop that leads to typical myointimal proliferation.
      However, the exact nature of the reprogramming induced by this microenvironment
      on recruited monocyte and macrophage phenotypes is ill defined. Human umbilical
      vein endothelial cells with a serum-starved condition (SSC) for 4 hours were used
      as a model of apoptotic endothelial cells. This conditioned medium was
      centrifuged to isolate the apoptotic bodies. Monocytes were harvested from
      healthy donors using Ficoll gradient and immunomagnetic selection. Blood monocyte
      derived macrophages (5-7 days of maturation) were exposed to centrifuged
      apoptotic cell-conditioned media for 24 hours. Cells were harvested for
      immunoblotting, and supernates were retained for enzyme-linked immunosorbent
      assay to determine cytokine and chemokine production. Macrophages generated less
      IL-6 and IL-8 when cultured in SSC compared with control. Immunoblotting for
      STAT3 (signal transducer and activator of transcription 3) in macrophages
      revealed that SSC increased STAT3 levels, which persisted after
      lipopolysaccharide stimulation. These results suggest that SSC attenuates the pro
      inflammatory phenotype in macrophages, through a STAT3-dependent mechanism.

PMID- 19857740
TI  - Endoscopic management of urologic complications following renal transplantation:
      impact of ureteral anastomosis.
AB  - OBJECTIVE: To evaluate the success of ureteral stent placement to treat or
      prepare for surgical treatment of urologic complications after renal
      transplantation, according to a type of ureteral anastomosis. PATIENT AND
      METHODS: From May 1989 to December 2006, we performed 703 kidney transplantations
      including 412 extravesical ureteroneocystostomy (according to Lich-Gregoire
      technique) and 265 transvesical ureteroneocystostomy (according to Politano
      Leadbetter technique). We retrospectively analyzed our endoscopic management of
      urinary leaks and ureteral strictures. The criteria of success were the
      feasibility to place a ureteral stent, permitting good drainage of the upper
      renal graft tract before further endoscopic or surgical treatment. RESULTS: Forty
      three urinary leaks or ureteral strictures occurred after extravesical
      ureteroneocystostomy (n = 21) or after Politano-Leadbetter anastomosis (n = 22).
      The success rate of endoscopic management was 75% (n = 16) for Politano
      Leadbetter anastomosis versus 53% (n = 11) for the Lich-Gregoire anastomosis.
      There was no statistical difference (P = .1). CONCLUSION: Ureteroneocystostomy
      according to Lich-Gregoire procedure were twice less complicated than those
      according to the Politano-Leadbetter technique, but were associated with a rate
      of failure of ureteral stent placement in urgency higher to 25%.

PMID- 19857739
TI  - De novo renal carcinoma in renal transplant recipients: effect of early
      treatment.
AB  - OBJECTIVE: To evaluate the epidemiology, diagnosis, and outcome of de novo renal
      cell carcinoma in renal transplant recipients. PATIENTS AND METHODS: From June
      1989 to August 2006, 800 renal transplant recipients were followed up annually by
      a urologist using abdominal ultrasonography or computed tomography. Renal lesions
      considered suspect were treated using extended nephrectomy. Incidence, diagnosis,
      histologic type, treatment, and outcome were analyzed in all patients. RESULTS:
      Thirty-three patients underwent nephrectomy because of suspect renal lesions
      including 22 de novo tumors in 21 native kidneys (renal clear-cell carcinoma in
      15 and papillary carcinoma in 7). All tumors were classified as pT1aN0M0. Mean
      (range) time after diagnosis was 25.6 (2.3-105.5) months. Only 1 patient died, at
      8 months after diagnosis. All other patients were alive at follow-up of 34.8 (2.8
      113.9) months. Five-year survival was 92%. CONCLUSION: The increased risk of
      tumor in renal transplant recipients leads us to propose extended nephrectomy in
      the case of suspect lesions in the native kidney. In our patients, 65% of
      patients had malignant lesions. Good prognosis for these localized tumors
      justified aggressive therapy even though 35% of transplant recipients were tumor
      free.

PMID- 19857741
TI  - Vitamin D metabolite-mediated hypercalcemia with suppressed parathormone
      concentration in Pneumocystis jiroveci pneumonia after kidney transplantation.
AB  - Pneumocystis jiroveci pneumonia (PJP) is a severe complication in
      immunocompromised hosts including transplant recipients. Hypercalcemia (HCa) is
      not a classic symptom of the disease. However, HCa (mean [SD; range], 2.90 [0.20;
      2.71-3.17] mmol/L) was detected in 5 patients with PJP at diagnosis. The HCa was
      associated with decreased concentrations of circulating parathormone (PTH), from
      294 (292) ng/L 3 to 6 months previously to 20 (23.5; 7-53) ng/L. Concentrations
      of 1,25-(OH)2 vitamin D, measured in 3 patients, were in the high normal range
      (54.66 [7.23; 225-66] microg/L), whereas 25-(OH) vitamin D concentrations were
      low (13.9 [2.17; 20-60] microg/L). After treatment with trimethoprim
      sulfamethoxazole for 21 days, 4 patients recovered and 1 died. Calcium and PTH
      concentrations rapidly returned to normal (2.36 [0.05] mmol/L and 89 [29.7] ng/L,
      respectively) at 2 months after the acute phase of the disease. Although fewer
      than 10 cases of PJP-associated HCa have been reported to date, it is possible
      that this association is more frequent than previously thought because our cases
      were detected during 2 years. As in other granulomatous disease-induced HCa,
      including fungal infections, it is likely that endogenous extrarenal production
      of 1-alpha-hydroxylase by activated macrophages and by interferon-gamma involved
      in granuloma formation results in increased conversion from 25-(OH) vitamin D to
      1,25-(OH)2 vitamin D and, consequently, in transient HCa and suppression of PTH
      secretion. Fortuitous detection of HCa in transplant recipients with pulmonary
      symptoms must raise suspicion of PJP or fungal infection.

PMID- 19857742
TI  - Long-term kinetics of a T-lymphocytes subset in kidney transplant recipients:
      relationship with posttransplant malignancies.
AB  - Immunosuppression is associated with a high incidence of malignancies among renal
      transplant patients. In this study, we investigated the relationship between CD4
      lymphopenia and the development of posttransplant malignancy (PTM) after
      induction therapies in renal transplant recipients (RTR). PATIENTS AND METHODS:
      This retrospective study included 966 RTR who were transplanted between 1993 and
      2005 and had a mean follow-up of 83 +/- 46 months. Induction with antithymocyte
      globulin (ATG) was employed in 747 patients, while remaining 219 recipients
      received anti-CD25 antibodies. CD4 T-cell counts determined yearly were
      correlated with the occurrence of PTM. RESULTS: Eighty-five (8.8%) patients
      developed a PTM: cutaneous neoplasia (n = 33), lymphoma (n = 14), noncutaneous
      solid cancer (n = 36). Only age was observed to be significantly different among
      patients with versus without PTM (48 +/- 10 vs 41 +/- 12 years; P < .001). An
      early CD4 lymphopenia (<300/mm(3)) was frequent after ATG as compared with anti
      CD25 induction (69.8% vs 12.1% at 3 months; P < .0001). The proportion of T CD4
      lymphopenic patients progressively decreased over time remaining stable at 5- and
      10-year follow-ups (12% and 10.8%, respectively). However, CD4 lymphopenia was
      not associated with a greater incidence of PTM. CONCLUSION: ATG induced CD4
      lymphopenia, which persisted in a small proportion of patients in the long term,
      but did not seem to be correlated with the occurrence of PTM.

PMID- 19857743
TI  - Long-term glomerular filtration rate in liver allograft recipients according to
      the type of calcineurin inhibitors.
AB  - The calcineurin inhibitors (CNI) cyclosporine micro emulsion (CyA-ME) and
      tacrolimus (Tac) both display renal and vascular toxicities. We undertook a
      single-center retrospective study among 149 surviving liver transplant
      recipients. The primary outcome was kidney function over 10 years posttransplant,
      evaluating the glomerular filtration rate (GFR) by the abbreviated Modification
      of Diet in Renal Disease formula with subsequent Kidney Disease Outcomes Quality
      Initiative staging. The secondary outcomes included correlations between CNI
      trough levels (C0), GFR, and items of cardiovascular toxicity. At 1 and 5 years,
      the mean GFRs were 74.2 and 76.9 mL/min/1.73 m(2) under Tac versus 62.8 and 66.0
      mL/min/1.73 m(2) under CyA-ME (P < .001). The mean value in favor of Tac was + 10
      mL/min/1.73 m(2). Distribution of GFR stages showed more Tac patients at stage 1
      or 2 and more at stage 4 or 5 under CyA-ME. There was no significant correlation
      between CNI-C0 and GFR. Switches between CNI or to mycophenolate mofetil did not
      show any significant GFR improvement. Patients under CyA-ME displayed
      significantly higher blood pressures with 3 requiring dialysis versus none under
      Tac. In conclusion, we observed that liver transplant patients under Tac
      maintained significantly better renal function with less progression to dialysis
      as compared with CyA-ME, indicating a lower renal and vascular (lower BP)
      toxicity.

PMID- 19857744
TI  - Rationale for monitoring cyclosporine concentration at 2 hours after
      administration in infants posttransplantation.
AB  - Therapeutic drug monitoring is critical to avoid overimmunosuppression or
      underimmunosuppression in young pediatric transplant recipients. The objective of
      this study was to examine cyclosporine (CsA) trough (C0) and 2-hour post-dose
      (C2) concentrations in the early period after liver transplantation (OLT) to
      determine whether CsA C2 monitoring is justified. Seventeen infants younger than
      2 years treated with CsA (Neoral) were monitored at C0. The biopsy-proved acute
      rejection rate was 65% at 3 months post-OLT. No correlation was observed between
      values at C0 and C2. Poor absorption of CsA was observed in most infants during
      the first 2 weeks post-OLT, as well as interindividual variability in CsA
      clearance. Exposure to CsA could not be estimated using either C0 or C2
      determinations in the early post-OLT period. As a marker of poor absorption, C2
      is useful but does not indicate delayed or rapid clearance of drug without
      simultaneous measurement of concentration at C0. We suggest the use of both C0
      and C2 monitoring, or AUC monitoring on an individual basis during at least the
      first 2 weeks post-OLT.

PMID- 19857745
TI  - Comparison of cyclosporine and tacrolimus in combination with rabbit
      antithymocyte immunoglobulins as induction therapy in cardiac transplantation.
AB  - Induction with rabbit antithymocyte immunoglobulins (RATG) for cardiac
      transplantation allows reduction of calcineurin inhibitor and reduces the
      incidence of acute rejection episodes (ARE). We compared induction with RATG
      combined with either cyclosporine (CsA) or tacrolimus (FK) in regard to the
      number of ARE in the first year after transplantation. We transplanted 111
      patients from 2000 to 2008 including 61 who received CsA-RATG, and 19, FK-RATG.
      At 3 months and 1 year the CsA group displayed 3.29 +/- 1.66 and 7.44 +/- 2.45
      ARE per patient of grade at least 1R respectively. The FK group showed 3.21 +/-
      1.71 and 8.13 +/- 2.07 episodes per patient (P = .86 at 3 months; P = .32 at 1
      year). Among ARE 2R or greater, the CsA group displayed 0.51 +/- 0.70 and 0.91 +/
      0.95 episodes per patient at 3 months and 1 year, while the FK group showed 0.15
      +/- 0.38 and 0.31 +/- 0.63 episodes, respectively (P = .09 at 3 months; P = .016
      at 1 year). Among type 3R ARE, the CsA group showed 0.11 +/- 0.32 and 0.13 +/-
      0.34 episodes, whereas the FK group experienced 0.05 +/- 0.23 and 0.05 +/- 0.23
      episodes at 3 months and 1 year, respectively (P = .44 at 3 months, P = .35 at 1
      year). The freedom rate from 1R, 2R, and 3R ARE was therefore similar between the
      two groups (P = .76, P = .14, and P = .23, respectively). Induction with FK-RATG
      tended to reduce the number of type 2R and greater rejection episodes per patient
      at 1 year after transplantation compared to CsA-RATG.

PMID- 19857746
TI  - The evolution of kidney function after lung transplantation: a retrospective
      cohort study.
AB  - BACKGROUND: Little information exists regarding the rate of kidney functional
      loss after lung transplantation. The aim of this study was to assess the
      evolution of kidney function after lung transplantation, seeking to identify a
      pretransplant glomerular filtration rate (GFR) threshold under which dual lung
      kidney transplantation should be considered. PATIENTS AND METHODS: We performed a
      single-center, retrospective cohort study among patients who received a first
      lung transplant. GFR was measured with the MDRD7 equation immediately before and
      up to 10 years after transplantation. A hierarchical model of linear regression
      was used to determine the evolution of GFR over time. RESULTS: We studied 241
      subjects whose mean GFR was 92 +/- 33 mL/min/1.73 m(2) immediately before
      transplantation. The GFR declined quickly during the first posttransplant month (
      24 mL/min/1.73 m(2) vs baseline; 95% confidence interval [CI]: -27, -21
      mL/min/1.73 m(2)). It decreased slightly between 1 and 12 months (-34 mL/min/1.73
      m(2) at 12 months vs baseline; 95% CI: -37, -31 mL/min/1.73 m(2)) and then
      stabilized up to 10 years after transplantation. GFR loss varied according to the
      baseline GFR. In patients with baseline GFR < or = 60 mL/min/1.73 m(2), the GFR
      declined by 9 mL/min/1.73 m(2) (95% CI = 6-15) at 1 year and was stable there
      after. CONCLUSION: GFR declines rapidly in the first month and at 1 year after
      lung transplantation, stabilizing thereafter. Because they are likely to develop
      eligibility for kidney transplantation in the 1 to 2 years following lung
      transplantation, we believe that dual lung-kidney transplantation should
      definitely be considered for subjects with a baseline GFR < or = 35 mL/min/1.73
      m(2).

PMID- 19857747
TI  - Human mesenchymal stem cells and immunosuppressive drug interactions in
      allogeneic responses: an in vitro study using human cells.
AB  - OBJECTIVES: The use of mesenchymal stem cells (MSC), which display
      immunosuppressive activity, seems to be a promising therapeutic approach in solid
      organ transplantation. However, little is known about their interactions with
      immunosuppressive drugs. The objective of this study was to assess these
      interactions in allogeneic responses. METHODS: We studied the effects on
      alloimmune responses in mixed lymphocyte reactions of MSC plus five agents
      cyclosporine, tacrolimus, rapamycin, mycophenolate acid (MPA), and dexamethasone
      (DEX). RESULTS: Human MSC isolated from bone marrow were characterized by their
      phenotype and their ability to differentiate into adipocytes or osteoblastes. MSC
      plus the agents inhibited allogeneic lymphocyte proliferation in a dose-dependent
      manner. Calcineurin inhibitors and rapamycin antagonized the inhibitory effect of
      MSC, whereas MPA promoted it and DXM did not modify it. CONCLUSION: MPA seems to
      be the best immunosuppressant to associated with MSC for transplanted patients.

PMID- 19857748
TI  - Stem cell therapy for the broken heart: mini-organ transplantation.
AB  - BACKGROUND: Myocardial infarction (MI) is characterized by irreversible loss of
      cardiomyocytes, resulting in impaired ventricular function. Stem cell therapy
      using autologous progenitor cells has emerged as a promising approach.
      Experimental studies have demonstrated that highly selected hematopoeitic stem
      cells, which are characterized by the presence of the surface markers CD34 and
      CD133, may contribute to repair of the acutely infarcted myocardium by inducing
      neovascularization, inhibiting apoptosis, and promoting cardiomyogenesis. We
      sought, to evaluate the intracoronary injection of CD133+ stem cells for cardiac
      repair in patients with dysfunctional myocardium after an acute MI. PATIENTS AND
      METHODS: In this Canadian randomized, double-blind, placebo-controlled, Phase I
      II study ("COMPARE-AMI"), we are evaluating the feasibility, safety, and efficacy
      of intracoronary injection of selected CD133+ stem cells for cardiac repair in
      patients with impaired cardiac function after successfully stented acute MI.
      Since November 2007, we have enrolled 14 patients in the study. Their mean age
      was 50.5 +/- 9.1 years, including 93% men. The culprit lesion was always on the
      left anterior descending artery (LAD). Their maximum troponin and CKMB levels
      were 8.4 +/- 6.1 microg/L and 322 +/- 225 U/L, respectively. RESULTS: Compared
      with the baseline, we observed a significant 8.7% improvement in left ventricular
      ejection fraction at 4 months follow-up, namely, from 41.3 +/- 5.5% to 50.0 +/-
      8.2% (n = 7; P = .008). There were no protocol-related complications. Our trial
      is designed to recruit 40 patients who are randomized 1:1 to receive CD133+ cells
      or placebo. PERSPECTIVE: There is a need to seek out new therapeutics for the
      treatment of ischemic heart disease addressing the early loss of viable myocytes.
      Stem cell transplantation has shown early promise; this appraisal needs well
      designed, controlled studies.

PMID- 19857749
TI  - A brief focus on memory cells in transplantation.
AB  - T and B memory cells are critical for host defences against pathogens. However,
      converging lines of evidence indicate that alloreactive memory T cells can play a
      detrimental role in the transplantation setting. This emergence of memory cells
      seems to be facilitated by several induction therapies and immunosuppressive
      agents, which lead to T cell loss. Herein, we briefly review some clinical and
      experimental observations from the literature, highlighting the immunological
      risk associated with enhanced T-cell memory responses.

PMID- 19857750
TI  - Injection of donor-derived OX62+ splenic dendritic cells with anti-CD4 monoclonal
      antibody generates CD4+CD25+FOXP3+ regulatory T cells that prolong allograft skin
      survival indefinitely and abrogate production of donor-specific antibodies in a
      rat model.
AB  - OBJECTIVE: To examine in a rat model the ability of donor dendritic cells and
      anti-CD4 monoclonal antibody (mAb) to generate donor-specific CD4+CD25+
      regulatory T cells (Tregs) and to evaluate the capacity of these Tregs to prolong
      skin allograft survival and abrogate the production of donor-specific antibodies
      after skin grafting. MATERIALS AND METHODS: OX62+ (nonplasmacytoid) splenic
      dendritic cells were isolated from Fischer rats using magnetic beads and injected
      (2 x 10(6)) into Lewis rat recipients with or without treatment with a
      nondepleting anti-CD4 (W3/25) mAb. After 4 weeks, splenic CD4+CD25+FOXP3+ T cells
      were harvested using magnetic beads from conditioned animals and injected (1 x
      10(6)) into naive Lewis recipients (day 1) before they received a skin graft from
      a Fischer (n = 4) or a third-party (Norway; n = 4) donor rat. Donor-specific
      antibodies were detected in recipient blood using flow cytometric cross-matches
      with donor lymphocytes from day 0 to day 30 after grafting. RESULTS: After
      injection of conditioned CD4+CD25+FOXP3+ T cells, Lewis recipients accepted skin
      grafts from Fischer donors indefinitely (>100 days) but rejected third-party skin
      grafts. Donor-specific antibodies were detected at low levels in only 1 recipient
      receiving conditioned Tregs before grafting. Naive Tregs did not prolong skin
      graft survival. CONCLUSION: These preliminary data suggest that splenic dendritic
      cells in combination with an anti-CD4 mAb induce donor-specific Tregs that
      indefinitely prolong allogeneic skin graft survival and inhibit donor-specific
      antibody production. Experiments are under way to determine whether this protocol
      can inhibit chronic lesions after heart transplantation in this model.

PMID- 19857751
TI  - Differential effect of cyclosporine and mycophenolic acid on the human regulatory
      T cells and TH-17 cells balance.
AB  - BACKGROUND: Beyond the usual TH1/TH2 polarization, a reciprocal pathway between
      FoxP3+ regulatory T cells (Tregs) and interleukin (IL)-17-secreting effector T
      cells (TH-17) has recently been identified. We have investigated the effects of
      two immunosuppressive drugs, cyclosporine (CsA) and mycophenolic acid (MPA) on
      the development of Treg/TH-17 cell responses. METHODS: We compared the influence
      of CsA and MPA on the transcription levels of FOXP3 (Treg marker) and IL17 (TH-17
      marker) in activated human peripheral blood mononuclear cells (PBMC). RESULTS:
      After 48 hours of activation, IL17 transcription was rapidly induced, remaining
      stable over 96 hours, whereas only a transient increase in FOXP3 was noted,
      suggesting that the Treg/TH-17 cell balance was tipped toward TH-17 during PBMC
      activation. The addition of either CsA or MPA did not affect the level of
      transcription of FOXP3. MPA but not CsA was found to significantly inhibit IL17
      expression by activated PBMC. This effect of MPA seemed to result from its
      capacity to hamper (1) the production of IL1beta by monocytes and (2) the
      expression of TIM-1 by CD4+ T cells, two key signals involved in human TH-17
      differentiation. CONCLUSION: Through a preferential inhibition of IL17, MPA might
      favorably influence the Treg/TH- 17 balance. Our results suggest that the
      immunosuppressive drugs used in the clinic may differentially influence
      lymphocyte polarization, including the newly identified TH-17 pathway.

PMID- 19857752
TI  - Inhibitory effects of cyclosporine on human regulatory T cells in vitro.
AB  - BACKGROUND: Inevitable hepatitis C virus (HCV) recurrence after liver
      transplantation is a major barrier to the survival of a transplanted liver. It
      may be promoted by immunosuppression and the emergence of CD4+CD25+ regulatory T
      cells (Treg). Treg cells can mediate the induction and maintenance of
      immunological self-tolerance as well as transplant tolerance. We investigated the
      effects of cyclosporine (CsA), a widely used immunosuppressive agent, on human
      CD4+CD25+ Treg cells. METHODS: Human CD4+CD25+ cells isolated from healthy donors
      were cultured in the presence of 40 or 400 ng/mL CsA. The suppressive activity of
      Treg was assessed in mixed leukocyte reactions (MLR) using CD25+ and autologous
      activated peripheral blood mononuclear cells (PBMC). Phenotype analysis (flow
      cytometric, Q-PCR) and cytokine production (ELISA) of Treg cells were then
      performed on cultures. RESULTS: CsA (40 or 400 ng/mL) inhibited the proliferative
      capacity of PBMC and CD4+CD25+ Treg in a dose-dependent manner. Interestingly,
      addition of 40 ng/mL CsA in MLR impaired the suppressive activity of CD4+CD25+
      cells, whereas a higher dose of CsA had no effect on Treg function. It appears
      that a therapeutic dose of CsA (40 ng/mL) did not change the phenotype of
      CD4+CD25+ T cells, but altered Treg activity by switching the regulatory to an
      inflammatory cytokine profile. CONCLUSION: CsA significantly impaired the
      function of CD4+CD25+ Treg cells by inducing interleukin-2 (IL-2) and interferon
      gamma (IFN-gamma) secretion. The present studies suggested that CsA may block the
      induction of immune tolerance and decrease the risk of hepatitis C recurrence.

PMID- 19857753
TI  - Preface: 16th annual meeting of the Belgian Transplantation Society.

PMID- 19857754
TI  - Discriminate liver warm ischemic injury during hypothermic machine perfusion by
      proton magnetic resonance spectroscopy: a study in a porcine model.
AB  - OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H MRS) is a technique to
      identify and quantify the composition of biofluids. Hypothermic machine perfusion
      (HMP) is an organ preservation method that has the potential to evaluate organ
      viability prior to transplantation by analyzing the composition of the perfusate.
      The aim of this study was to use (1)H MRS to examine the perfusate during HMP of
      porcine livers exposed to warm ischemia (WI) and to identify potential biomarkers
      of liver viability. MATERIALS AND METHODS: Porcine livers underwent 4 hours of
      HMP using kidney perfusion solution-1 (KPS-1) as perfusate after exposure to in
      situ WI of 0 (n = 6) or 2 hours (n = 5). Samples of the perfusate were taken at
      the start/end of HMP. Lactate and aspartate aminotransferase (AST) in the samples
      were measured biochemically as surrogates of the WI-induced damage. MRS
      acquisition was conducted on a 9.4 Tesla (400 MHz) high-resolution system.
      RESULTS: AST increased significantly during 4 hours of HMP within groups (P <
      .02) and discriminated WI injury significantly from the start to the end of HMP
      (P < .03). (1)H MRS showed significantly elevated signal intensity of lactate,
      alanine, and histidine during HMP within both groups (P < .02). Furthermore,
      alanine and histidine were significantly higher in the WI group than in the
      control group at the end of HMP (P = .011 and P = .038, respectively).
      CONCLUSION: AST, alanine, and histidine in HMP perfusate discriminated WI injury
      on porcine liver grafts and might be potential biomarkers of liver viability.

PMID- 19857755
TI  - A retrospective monocenter review of simultaneous pancreas-kidney
      transplantation.
AB  - OBJECTIVE: Herein we have reviewed a consecutive series of simultaneous pancreas
      kidney (SPK) transplantations performed at our institution over a 6-year period.
      PATIENTS AND METHODS: The study population included 22 patients (15 males and 7
      females) who underwent SPK transplantation between 2001 and 2007. The mean
      recipient age was 47 years (range, 26-63 years). Eighteen patients suffered type
      1 and 4 type 2 diabetes mellitus. The mean donor age was 33 years (range, 14-56
      years). The mean HLA match was 2.1 (range, 1-5). Immunosuppressive treatment
      consisted of basiliximab induction followed by tacrolimus, mycophenolate mofetil,
      and prednisone. RESULTS: The mean hospital stay was 20 days (range, 11-52 days).
      After a mean follow-up of 44 months (range, 17-88 months), patient, kidney, and
      pancreas graft survivals were 86%, 82%, and 73%, respectively. Two patients died
      in the immediate postoperative period due to, respectively, disseminated
      intravascular coagulation and pulmonary embolism. A kidney graft was lost due to
      early hyperacute rejection. Other early complications associated with the
      pancreas graft included 2 cases of immediate reperfusion defects that led to
      early vascular thrombosis in 1 patient and a duodenal graft fistula in the other
      patient; a third patient developed type 2 diabetes mellitus. Beyond the
      postoperative period, graft loss was limited to 1 case of noncompliance to the
      immunosuppressive medications and 1 death secondary to pulmonary infection with a
      functional allograft after 4 years. CONCLUSIONS: SPK transplantation is a valid
      therapeutic option for patients with insulin-dependent diabetes mellitus and
      renal failure due to diabetic nephropathy. The main complications of SPK
      transplantation occur in the immediate postoperative period consequent to
      vascular or rejection processes.

PMID- 19857756
TI  - Balancing efficacy and toxicity of kidney transplant immunosuppression.
AB  - Late renal allograft loss is mainly the result of progressive histological
      damage. Both underimmunosuppression (rejection phenomena) and
      overimmunosuppression (calcineurin inhibitor nephrotoxicity) contribute to the
      progression of chronic histological damage. The current study was performed to
      elucidate the complementary impact of immune and nonimmune phenomena on renal
      allograft histology and function. By performing protocol biopsies, it was
      demonstrated that clinical and subclinical acute cellular rejection phenomena
      continue to play important roles, despite the use of the powerful combination of
      tacrolimus, mycophenolate mofetil, and steroids. Next to immune phenomena, the
      importance of nonimmune factors in renal allograft histological evolution was
      shown in protocol biopsy studies. Both in adult and in pediatric renal allograft
      recipients, the characteristics of the donor kidney (donor age, size discrepancy)
      appeared to be major determinants of the histological and functional evolution.
      This impact of donor characteristics was not only important in the immediate
      peritransplantation period, it was also shown that higher donor age increased the
      risk for progressive posttransplant histological injury and calcineurin inhibitor
      nephrotoxicity. Systemic levels of tacrolimus, if kept within a relatively narrow
      target window, were not associated with a risk for calcineurin inhibitor
      nephrotoxicity. However, we observed a significant association between renal
      allograft histology and P-glycoprotein (ABCB1) gene polymorphisms and expression,
      suggesting a role of this protein in the individual susceptibility to calcineurin
      inhibitor nephrotoxicity. Finally, the interplay between immune and nonimmune
      phenomena was demonstrated by the association between donor origin (deceased
      versus living) and local renal complement gene expression, by using whole-genome
      expression microarrays.

PMID- 19857757
TI  - Biliary strictures after liver transplantation: risk factors and prevention by
      donor treatment with epoprostenol.
AB  - Biliary strictures (BS), a major complication after orthotopic liver
      transplantation (OLT), cause morbidity, mortality, graft loss, and increased
      costs. The virtually unchanged incidence of BS (approximately 10%-25%) suggests
      that they are not simply "technical" in origin, but probably represent a mucosa
      ischemic injury inherent in the transplantation procedure. To study risk factors
      for BS, we analyzed 403 OLTs performed between January 1, 1997 and December 31,
      2006, at a single center, excluding cases of regraft or death within 1 month. The
      average time to the diagnosis of the BS was 253 days (range, 7-1002 days). Upon
      univariate analysis, the absence of flushing of donor bile ducts, an imported
      versus a locally procured liver, and rejection were risk factors for BS. In
      contrast, the following factors were protective: donor cardiac arrest followed by
      resuscitation (suggesting an ischemic preconditioning effect) as well as addition
      of epoprostenol to and pressurization of the preservation solution. Patients with
      higher postoperative peak values of transaminases, bilirubin, alkaline
      phosphatase, and gamma glutamyl transpeptidase were at greater risk for later
      development of BS. Donor hypotension, donor age, donor intensive care unit (ICU)
      stay, type of preservation, positive cross-match, cold and warm ischemia times,
      sequential versus simultaneous portal/arterial reperfusion, as well as
      cytomegalovirus (CMV) infection were not risk factors for BS. Upon multivariate
      analysis, only epoprostenol and pressurization offered protection from BS. In
      conclusion, this study 2 novel points: (1) patients with high(er) transaminase
      values and cholestasis early postoperatively are at greater risk to develop later
      BS and require close monitoring and (2) donor maneuvers for better flushing and
      preserving peribiliary vascular plexus and biliary mucosa (epoprostenol and
      pressurization of preservation solution) offer protection from BS.

PMID- 19857758
TI  - Improved results for adult split liver transplantation with extended right lobe
      grafts: could we enhance its application?
AB  - OBJECTIVE: Split liver transplantation (SLT) allows grafting of 2 recipients with
      1 allograft. Results of adult SLT have improved since its first introduction.
      Children benefit most from SLT, while among some adult liver transplanters there
      are concerns about splitting a liver, turning a good quality graft into a
      marginal one. We performed a single center retrospective review to address this
      issue. PATIENTS AND METHODS: Between June 2001 and August 2008, we performed 22
      extended right liver graft (eRLG) transplantations in 21 adult patients. RESULTS:
      Eleven donors (50%) did not meet the Eurotransplant criteria for optimal donors.
      Forty-one percent of eRLG donors showed hemodynamic instability at the time of
      harvest. Eighteen (82%) splitting procedures were performed ex situ. The main
      indications for transplantation were alcoholic liver cirrhosis (32%), hepatitis C
      related cirrhosis (18%), and acute liver failure (18%). Mean recipient age was 54
      years (range, 17-69 years); median Model for End-Stage Liver Disease (MELD) score
      was 15 (range, 7-40). Patients were followed for a median of 16 months (range, 4
      92 months) following transplantation. We observed 5 (23%) vascular and 3 (14%)
      biliary complications. Overall patient survival was 84% at 3 years; overall graft
      survival was 79%. For the 11 patients who had undergone transplantation after
      2007, we observed a 100% patient and graft survival. CONCLUSION: After an initial
      learning curve and provided careful selection, exceptions to classical donor
      criteria for splitting can be accepted with successful outcomes comparable to
      those after whole liver transplantation.

PMID- 19857759
TI  - C-reactive protein in bronchoalveolar lavage fluid is associated with markers of
      airway inflammation after lung transplantation.
AB  - BACKGROUND: C-reactive protein (CRP), an acute-phase marker of systemic
      inflammation, may also be a local regulator of the pulmonary immune system. Its
      role in lung transplantation (LT), however, is unclear. We hypothesized that CRP
      in bronchoalveolar lavage (BAL) fluid might be associated with airway
      inflammation or remodeling. Therefore, it could play a role in the development of
      bronchiolitis obliterans syndrome (BOS). PATIENTS AND METHODS: A total of 100 LT
      recipients who had undergone transplantation between August 2001 and August 2005
      were included in the current cross-sectional study. Patients who were evaluated
      at 90 days after LT were categorized as either stable (n = 36), colonized (n =
      25), or suffering from infection (n = 16) or acute rejection (n = 23). BAL CRP,
      cell differentials, and interleukin (IL), IL8, transforming growth factor beta
      (TGFbeta), and vascular endothelial growth factor (VEGF) protein levels, as well
      as blood leukocytosis, plasma CRP, and forced expiratory value in 1 second
      (FEV(1); % predicted) were compared between groups. We analyzed the correlation
      of BAL CRP with inflammatory or remodeling markers and FEV(1). RESULTS: Compared
      with stable LT recipients, BAL CRP was significantly increased in patients with
      infection or acute rejection (P < .0001), but not in those with colonization.
      Generally, BAL CRP levels positively correlated with BAL total cell count,
      neutrophilia, and IL8 levels, as well as with plasma CRP levels (P < .0001). An
      inverse correlation was observed with BAL macrophages (P < .01), VEGF (P <
      .0001), and FEV(1) (P < .0001). Only a trend for a positive, respectively inverse
      correlation was seen for BAL IL6 and TGFbeta. CONCLUSIONS: The current data
      corroborate a possible role for CRP in airway inflammation after LT. Its
      importance for BOS should therefore be further elucidated.

PMID- 19857760
TI  - Reproducible model for kidney autotransplantation in pigs.
AB  - OBJECTIVE: Several porcine models have been employed to study mechanisms of warm
      ischemia, cold ischemia, and ischemia reperfusion injury, but the
      technical/surgical aspects of these models and their possible pitfalls have not
      been fully described in detail. The goal of the present study was to develop and
      optimize a porcine kidney autotransplantation model. MATERIALS AND METHODS:
      Eleven female pigs (24-51 kg) underwent a left ureteronephrectomy. The procured
      kidney was flushed with 500 mL of histidine-tryptophan-ketoglutarate preservation
      solution and subsequently cold stored in University of Wisconsin preservation
      solution. An autotransplantation was performed 18 hours later, following
      contralateral nephrectomy. Serum creatinine and urine production were assessed
      posttransplantation. Pigs were sacrificed at 10 days posttransplantation.
      RESULTS: Nine pigs showed functioning grafts, immediately producing urine
      posttransplantation. The serum creatinine values in these pigs followed a bell
      shaped curve with peak values at day (D)2-D3. Two renal artery thromboses were
      observed; the venous anastomosis was prone to stenosis in 6 cases. These
      technical complications influenced posttransplant observations. Renal artery
      thrombosis resulted in anuria and increased serum creatinine levels. A stenotic
      renal vein was associated with a greater peak of serum creatinine. These
      complications were prevented by modifying the surgical technique accordingly.
      CONCLUSIONS: We developed and optimized a reproducible model of porcine kidney
      autotransplantation. Herein we have demonstrated the importance of a proper
      surgical anastomotic technique to avoid inflow or outflow obstruction that might
      jeopardize posttransplant kidney function. This clinically relevant model offers
      the possibility to study various aspects related to kidney preservation without
      the interference of an allogeneic immune response.

PMID- 19857761
TI  - An easy and reproducible model of kidney transplantation in rats.
AB  - OBJECTIVE: Kidney transplantation in rats is an important research model. Various
      methods have been reported, but there is no "standard operation." We investigated
      a 1-stage versus a 2-stage native nephrectomy and the type of ureteral
      anastomosis seeking to establish a standard, reproducible and successful method.
      MATERIALS AND METHODS: We used PVG (RT1c-RT1Ac: B/Dc) male rats, weighing
      approximately 200 to 250 g, that underwent transplantation after right recipient
      nephrectomy. Left recipient nephrectomy was performed either 10 days later or
      simultaneously. The ureteric anastomosis was fashioned 2 ways: using a ureteral
      stent or by bladder insertion. RESULTS: Urinary complications (obstruction or
      reflux) were observed in 77.8% when a ureteral stent was used for the ureteric
      anastomosis versus 28.6% when using the bladder insertion technique (P = .0211).
      Transplanted rats with nephrectomy of both native kidneys at the time of grafting
      showed a perioperative mortality of 70%, whereas those hosts with a 2-stage
      nephrectomy displayed a mortality rate of 22% (P = .0025). CONCLUSIONS: The
      bladder insertion technique reduced the incidence of urological complications in
      rats. In addition, unilateral native nephrectomy at the time of operation with
      delayed contralateral nephrectomy was better tolerated than simultaneous
      bilateral nephrectomy. These 2 surgical variants allowed us to perform kidney
      transplantation with a high degree of success.

PMID- 19857762
TI  - Rescue of a marginal liver graft by sequential treatment with molecular adsorbent
      recirculating system and transjugular intrahepatic portosystemic shunt: a case
      report.
AB  - A 53-year-old man with alcoholic liver cirrhosis underwent orthotopic liver
      transplantation (OLT) using a marginal graft. Persistent cholestasis post-OLT was
      successfully treated using a molecular adsorbent recirculating system (MARS).
      Afterwards, the patient developed refractory ascites, which was controlled by a
      transjugular intrahepatic portosystemic shunt (TIPS). TIPS reduction and
      eventually occlusion was necessary due to the development of encephalopathy.
      Despite TIPS occlusion, the ascites did not relapse probably because of the onset
      of other adaptive mechanisms. MARS and TIPS used sequentially were capable of
      rescuing a liver graft, thereby avoiding the morbidity and mortality associated
      with early retransplantation and sparing a liver graft from the donor pool.

PMID- 19857763
TI  - Liver transplantation is feasible in super-obese patients: a case report.
AB  - Short- and long-term results of liver transplantation in morbidly obese patients
      may be impaired compared with the general transplant population. As a
      consequence, severe obesity has been considered to be a relative contraindication
      to liver transplantation in many centers. Surgically, liver transplantation in
      severe obesity may be challenging. Moreover, obesity may lead to an increased
      rate of early and late medical complications. Herein we have reported successful
      liver transplantation in a super-obese patient (body mass index, 55.1 kg/m(2))
      who had developed terminal acute-on-chronic liver disease. In the first 6 months
      of follow-up, the patient underwent a severe diet that led to a significant
      weight loss reduction to a body mass index of 39 kg/m(2). This report of
      successful liver transplantation in a super-obese patient suggests that severe
      obesity should not be considered to be an absolute contraindication to liver
      transplantation.

PMID- 19857764
TI  - Budd-Chiari syndrome complicating hepatic sarcoidosis: definitive treatment by
      liver transplantation: a case report.
AB  - Sarcoidotic involvement of the liver is frequent, albeit uncommonly symptomatic.
      Severe complications are rare, but may seldom require liver transplantation. Budd
      Chiari syndrome has been described in a few patients with hepatic sarcoidosis.
      Herein we have reported the case of a young woman suffering from hepatic
      sarcoidosis who developed severe cholestasis and chronic Budd-Chiari syndrome.
      She successfully underwent orthotopic liver transplantation (OLT) and is
      asymptomatic with normal liver function at 3 years follow-up. Histopathological
      assessment of the liver explant demonstrated a florid granulomatous process, with
      involvement of the large intrahepatic veins, providing an anatomical basis for
      the vascular flow disturbances. This case adds further evidence that liver
      transplantation may be the curative treatment for complicated sarcoidotic liver
      disease.

PMID- 19857766
TI  - Acral myxoinflammatory fibroblastic sarcoma in a renal transplant patient: a case
      report.
AB  - Herein, we have reported a case of a 62-year-old patient who presented at 10
      months after renal transplantation with a nodular mass on the dorsum of his foot.
      Local excision was performed and an acral myxoinflammatory fibroblastic sarcoma
      was diagnosed. This is a rare, low-grade sarcoma with a high rate of local
      recurrence, sometimes leading to amputation. Metastasis to the lungs and liver
      has been reported, but is rare. Since our patient received triple
      immunosuppressive therapy, our major concern was a much more aggressive behavior.
      However, more than 2 years after excision of the tumor, the patient is still free
      of disease.

PMID- 19857765
TI  - Fulminant hepatic failure induced by venlafaxine and trazodone therapy: a case
      report.
AB  - Although acute hepatitis may be a side effect of many medications, most cases are
      reversible after treatment interruption, and fulminant hepatic failure (FHF) is
      rare. Venlafaxine and trazodone are 2 popular antidepressant agents. Alteration
      of liver enzyme levels has been reported as a side effect of these drugs at
      normal doses. Herein we have reported the case of a 48-year-old woman without any
      previous history of liver disease, who developed fulminant liver failure after 4
      months of venlafaxine and trazodone therapy. She required liver transplantation,
      a procedure that was successful with full patient recovery. The first 5 years of
      follow-up were uneventful. This case documented that venlafaxine and trazodone at
      normal doses can produce severe liver toxicity. Liver tests should be monitored
      regularly in patients who receive this therapy.

PMID- 19857767
TI  - Preface: 1st Ibero-American Congress of Transplant Coordination.

PMID- 19857768
TI  - Mission and challenges of the Ibero-American Society of Transplant Coordinators.

PMID- 19857769
TI  - The 40 donors per million population plan: an action plan for improvement of
      organ donation and transplantation in Spain.
AB  - INTRODUCTION: Spain has been showing the highest rate of deceased donor organ
      recovery in the world for a whole country, namely, 33-35 donors per million
      population (pmp) during the last years. This activity is attributed to the so
      called Spanish Model of organ donation, an integrated approach to improve organ
      donation since the start of the Organizacion Nacional de Trasplantes (ONT) in
      1989. However, in 2007 there were 7/17 regions with >40 donors pmp and a marked
      regional variability. Thus, ONT has set a large-scale, comprehensive strategy to
      achieve a substantial improvement in donation and transplantation in Spain in the
      coming years: The 40 Donors pmp Plan. PURPOSE AND SCOPE: The overall objective is
      to increase the average rate of deceased donors to 40 pmp between 2008 and 2010.
      The areas of improvement, specific objectives, and actions have come from deep
      reflection on the data and the material generated from multidisciplinary
      discussions and open consultation with the donation and transplantation
      community. KEY AREAS SELECTED FOR ACTION: Detection and management of brain-dead
      donors, with 4 specific subareas: access to intensive care units, new forms of
      hospital management, foreigners and ethnic minorities, and evaluation/maintenance
      of thoracic organ donors. Expanded criteria donors, with 3 subareas: aging,
      donors with positive tests to certain viral serologies, and donors with rare
      diseases. Special surgical techniques. Donation after cardiac death.

PMID- 19857771
TI  - International indicators of donation and solid organ transplantation.
AB  - The main goal of any organ procurement organization (OPO) is to offer the
      greatest number of organs achievable with the goal of reducing mortality and the
      waiting list time of patients. Evaluation of OPO activity is mandatory to
      identify causes of missed potential donors seeking to implement changes in steps
      susceptible of improvement. In this review, we have presented the classical
      indicators of brain death along with new indicators. We observed that when the
      donor generation capacity is adjusted to the deaths, the indicator is more
      reliable for comparisons of countries with different mortality rates. We
      concluded that the indicators are complementary, because they measure different
      aspects of the process. To have a better understanding of the situation, country,
      institution, or hospital, one should simultaneously use all of the indicators.

PMID- 19857770
TI  - Teenager donation: investigation of 848 high school students.
AB  - AIMS: The aims of this study were to quantify donors among the investigated area,
      quantify arguments and myths about the donation and transplantation process, and
      fix predetermined donation variables in a logistical model. MATERIALS AND
      METHODS: We used an analytical, prospective design, using 848 students from 13
      high schools in the Velez Sarsfield Hospital area in an open-closed inquiry.
      RESULTS: Females were 57.74% and average age was 16.64 +/- 0.06 years, including
      65.09% Catholics. The 642 potential donors represented 75% of the study
      population with the fundamental aim being to "give life" (44.85%). The 193
      (22.75%) opposed subjects cited as a principal reason fear and distrust (40.41%).
      There were 40.21% who had discussed the donation subject with their families. In
      our study 76.41% believed that human organ traffic exists and 36.88% thought that
      it is due to corruption. Also, 56.01% fear premature extraction of their organs.
      In addition, 73.23% of teenagers considered that individuals who refused to
      donate have the right to receive organs (P = not significant between donors and
      not a donor). The family discussion and the lack of fear about premature
      extraction were donation signals. About the low level of donation 43.27% blamed
      the government (lack of campaigns, information, and knowledge) whereas other
      reasons were fear, lack of clarity and distrust. In our study 49.17% seemed to
      wish to increase donation if they received more information. CONCLUSIONS:
      Individuals predispose to donation represented the great majority of the queried
      teenagers; education and family discussion were remarkable factors favoring the
      decision.

PMID- 19857772
TI  - Presence in the media of the topic "donation and transplantation of organs and
      tissues" during the 2005 to 2007 period in Venezuela as a strategy to improve its
      perception in Venezuelan society.
AB  - INTRODUCTION: Media are main allies to encourage donation and transplantation. We
      sought to quantify the presence in the media of the topic "Donation and
      transplantation (D/Tx)" during the period 2005 to 2007 and to determine the
      relationship between the volume of information issued by the media and indexes
      related to the topic. METHODS: We conducted a systematic recording of the news on
      the topic of D/Tx in print, radio, and television during 2005 to 2007. RESULTS:
      There was an increased presence in the media by 100% in 2005 and 2006, and by
      200% in 2007. The presence in print media was greater than radio (249 +/- 31.5 vs
      131 +/- 5.49; P = .05) or television (249 +/- 31.5 vs 92 +/- 7.12; P = .01). We
      observed a positive correlation between the total number of contacts versus the
      number of registered volunteer donors (R(2) = 0.9713) and number of contacts
      versus total number of transplants from cadaveric donors (CTX; R(2) = 0905). The
      index CTX per million population increased by 30% (2006 vs 2005) and 100% (2007
      vs 2005). The percent of family refusals fell from 41% in 2005 to 34% in 2006 and
      to 31% in 2007. The rate of donors per million population grew steadily from 1.8
      in 2005 to 2.3 in 2006, and to 3.6 in 2007. CONCLUSION: The sustained increase in
      D/Tx briefing as a strategy of Sistema de Procura de Organos y Tejidos has helped
      to foster a positive perception that is reflected in the increased rate of
      donation and transplantation in Venezuela.

PMID- 19857773
TI  - Identification of variables that influence brain-dead donors' family groups
      regarding refusal.
AB  - OBJECTIVE: To identify the variables that influenced brain-dead donor family
      groups to refuse donation. METHODS: The Tissue and Organ Procurement System in
      Venezuela designed a tool to register some phases of a family interview performed
      by transplant coordinators. This tool analyzed three phases. The first phase of
      the interview allowed the coordinator to evaluate the communication quality with
      the family group during a brain-death notification. The second phase assessed how
      families understood this notification, and the third phase identified the family
      grief sequence. Among the 186 interviews during 2007 to procure tissues and
      organs for transplantation, 37.63% (n = 70) concluded as family refusals. A
      retrospective study sought to analyze these results. RESULTS: The average time
      between notification of brain death and the first approach to the family was 8.78
      hours. Setting a place for interviews was done in 91.10% of cases. Previous
      knowledge about donation was seen in only 53.33% of cases. The main phase of
      family grief identified was denial (80%). The five reasons for family denial
      were: absolute denial, family disagreement, uncertainty about the destination of
      the donated organs and tissues, fear about deformation of the donor's body, and
      lack of acceptance of brain death. CONCLUSIONS: Brain-death notification produced
      a deep sadness among family groups. There was a lack of knowledge regarding
      donation of tissues and organs. It was impossible to quantify the time needed by
      families to understand and accept brain death and to identify the grief sequence
      in order to avoid family refusals.

PMID- 19857774
TI  - Controversial points in organ donor management.
AB  - There are still many controversial aspects regarding which method is best for
      managing organ donors to prevent, lessen, or even reverse the organ alterations
      associated with brain death. Fundamental aspects are the management of an
      adequate perfusion pressure, hormone restoration, and opposition of the
      inflammatory state associated with brain death. Once volume has been normalized,
      it is necessary to administer vasoactive drugs, including catecholamines to re
      establish the loss of sympathetic tone at the vascular and myocardial level. It
      is impossible to define the ideal or maximal catecholamine dose because it
      depends on the donor's vascular tone, vascular reactivity, and pharmacokinetic
      variability characteristic of critical patients, particularly organ donors. To
      control early onset of diabetes insipidus, it is necessary to administer
      desmopressin. At present there are insufficient clinical studies to show the
      usefulness of triiodothyronine. Furthermore, due to its limited availability,
      elevated cost, and probable side effects, the use of this hormone is not
      justified. More importance is being given to the negative influence of the
      inflammatory state associated with brain death, which has repercussions on organ
      viability and probably influences the prevalence of rejection episodes. Meanwhile
      in organ donor management, we recommend the use of 15 mg/kg of methylprednisolone
      as soon as possible. Contrary to triiodothyronine, the potential benefit of its
      immunomodulatory effects, its low cost, and the absence of major side effects
      justify this recommendation.

PMID- 19857775
TI  - Quality management indicators for tissue banks: an operative model from the
      period of 2002-2007.
AB  - AIM: The purpose of this study was to determine a specific indicator model to
      evaluate the Quality Management System (QMS) in Tissue Banks (TB) for deceased
      and/or live donors. METHODS: Quantitative Indicators for Quality Management are
      considered for deceased donors as the origin of therapeutic tissues. A glossary
      of definitions was established (also applicable for tissues from live donors):
      Deceased Therapeutic Real Donors (DTRD), donors that were processed and at least
      1 tissue was harvested for a therapeutic purpose; Deceased Effective Donors
      (DED), DTRD in which 1 or more tissues were validated, stored, and/or grafted;
      Processed Tissues (PT), number of tissues harvested from a DTRD, which were
      processed and counted as final product units; Validated Tissues (VT), number of
      tissues as final product units, which fulfilled quality criteria to be grafted;
      Grafted Tissues (GT), number of transplanted tissues for therapeutic purposes;
      and Grafted Patients (GP), number of patients who were grafted with validated
      tissues. MANAGEMENT QUANTITATIVE INDICATORS: Deceased donors were considered from
      2002 to 2007. The total number of tissues was 15,363: Productivity Index (PI), PI
      = DED/DTRD; Processing Quality Rate (PQR), PQR = VT/PT%; Productivity Efficiency
      per Donor (PED), PED = VT/DED; Grafted Tissues Coefficient (GTC), GTC = GT/VT;
      and Grafted Patients Index per Donor (GID), GID = GP/DED. RESULTS: Results were
      as follows: PI = 0.80; PQR = 76%; PED = 30.99; GTC = 0.93; and GID = 4. In our
      study, 80% of DTRD produced VT (PI = 0.80), which represented 76% of PT (average,
      31 final products per donor). Also, 93% of the VT were grafted with 5 patients
      grafted per donor. CONCLUSIONS: Defined variables resulted in useful tools to
      evaluate QMS in a TB.

PMID- 19857776
TI  - Guidelines to implement quality management systems in microbiology laboratories
      for tissue banking.
AB  - Human tissues for implants are a biomedical product that is being used more
      frequently by many medical disciplines. There are infections in the patients
      related to the implanted tissues. The early detection of infections transmitted
      by blood and the microbiological study of tissues before their clinical use are
      strategies in tissue banks to prevent these situations. This work sought to
      contribute to establish the bases for the operation of a laboratory applied to
      the microbiological quality control of tissues. Based on classical
      microbiological principles, we defined the operation of microbiological control
      and tissues sterilization since 2003. We determine lists of acceptable
      microorganisms for every tissue, criteria for the interpretation of results, and
      a diagnostic algorithm of microbiological quality. We observed that the
      circumstances of donor death can be a determinant of the quality. The environment
      and the operator should be investigated as probable sources of contamination in
      outbreaks. The criteria of work based on a solid methodology must help to avoid
      the transmission of infections between donor and recipient. This is a critical
      point in the quality management of a tissue bank.

PMID- 19857777
TI  - Improved results for adult split liver transplantation with extended right lobe
      grafts: could we enhance its application?
AB  - OBJECTIVE: Split liver transplantation (SLT) allows grafting of 2 recipients with
      1 allograft. Results of adult SLT have improved since its first introduction.
      Children benefit most from SLT, while among some adult liver transplanters there
      are concerns about splitting a liver, turning a good quality graft into a
      marginal one. We performed a single center retrospective review to address this
      issue. PATIENTS AND METHODS: Between June 2001 and August 2008, we performed 22
      extended right liver graft (eRLG) transplantations in 21 adult patients. RESULTS:
      Eleven donors (50%) did not meet the Eurotransplant criteria for optimal donors.
      Forty-one percent of eRLG donors showed hemodynamic instability at the time of
      harvest. Eighteen (82%) splitting procedures were performed ex situ. The main
      indications for transplantation were alcoholic liver cirrhosis (32%), hepatitis C
      related cirrhosis (18%), and acute liver failure (18%). Mean recipient age was 54
      years (range, 17-69 years); median Model for End-Stage Liver Disease (MELD) score
      was 15 (range, 7-40). Patients were followed for a median of 16 months (range, 4
      92 months) following transplantation. We observed 5 (23%) vascular and 3 (14%)
      biliary complications. Overall patient survival was 84% at 3 years; overall graft
      survival was 79%. For the 11 patients who had undergone transplantation after
      2007, we observed a 100% patient and graft survival. CONCLUSION: After an initial
      learning curve and provided careful selection, exceptions to classical donor
      criteria for splitting can be accepted with successful outcomes comparable to
      those after whole liver transplantation.

PMID- 19857778
TI  - Brain death epidemiology in Uruguay and utilization of the Glasgow coma score in
      acute brain injured patients as a predictor of brain death.
AB  - OBJECTIVE: The knowledge of brain death (BD) epidemiology and the acute brain
      injury (ABI) progression profile are relevant to improve public health programs,
      organ procurement strategies, as well as intensive care unit (ICU) protocols
      aiming to increase the detection of potential donors. The aim of this study was
      to analyze the BD epidemiology and the ABI progression profile among subjects
      admitted to ICUs with a Glasgow Coma Score (GCS) < or = 8. MATERIALS AND METHODS:
      This was a prospective, observational study of BD reported to the National
      Institute of Donation and Transplantation from 2000-2006. The patients with ABI
      and GCS < or = 8 who were admitted to 5 ICUs with In-hospital Transplant
      Coordination were analyzed over the period of 2005-2007. RESULTS: The BD
      detection increased from 28.7 in 2000 to 58.5 BD pmp in 2006. The real donor
      global rate increased from 10 to 24.6 pmp from 2000 to 2006. The ABI patients
      with GCS < or = 8 had a global mortality rate of 56%, including 23.4% who evolved
      to BD. CONCLUSIONS: This study showed a 200% increment of detected BD and 150% of
      real donors, although these results are still below the international figures.
      GCS follow-up appeared to be a good tool to predict the BD outcome. The follow-up
      of patients with ABI allowed us to improve our BD detection strategy.

PMID- 19857779
TI  - Three decades of the history of donation and transplantation in Uruguay.
AB  - AIM: The aim of this study was to analyze the evolution of the legal framework,
      health system of donation, and transplantation of cells, tissues, and organs,
      measured based on processes and rates from 1978 to 2008 in Uruguay. MATERIALS AND
      METHODS: We analyzed 3 decades (1978-1988/1989-1998/1999-2008) by the following
      evaluation: the legislation, donation and transplantation system, procurement,
      registration of pre-state of voluntary donations, actual donations and
      transplantation rates of solid organs (kidneys, heart, liver, and pancreas), and
      rates of donation and transplantation of tissues (corneal and laminar [skin,
      amniotic membrane, and fascialata]), of cardiovascular elements (valves and
      vases), and of ostearticular tissues (bones and tendons). RESULTS AND
      CONCLUSIONS: Uruguay has maintained continuous governmental politics in donation
      and transplantation. In the last decade the elaboration of a strategic plan by
      promoting Laws and Decrees of Encephalic Death, Presumed Donation and Security of
      Cells and Tissues, as well as the creation of the Unit Procurement, the
      registration of nonrelated donors for hematopoietic stem cells, and the re
      engineering of tissue banking, has shown a significant increase in deceased
      donation and cadaveric transplantation, reaching the first highest overall donor
      rate in Latin America with 24/pmp multiorgan donors.

PMID- 19857780
TI  - Uruguayan experience with cryopreserved arterial homografts.
AB  - INTRODUCTION: We analyzed the Uruguayan experience with cryopreserved arterial
      homografts. We studied 55 medical records in the period from June 9, 2000 to
      April 7, 2007, including 41 from males and 14 from females, ranging from 36-78
      years of age. The clinical indications were as follows: Group 1,
      revascularization of infrainguinal atherosclerotic occlusive disease by bypass
      due to the lack of availability of a suitable vein (n = 35); Group 2,
      substitution of an infected prosthetic grafts (n = 15); and Group 3,
      arteriovenous fistula (AVF) after failure of previous prosthetic loops by
      repeated thrombosis and/or infection in the absence of a vein (n = 5). RESULTS:
      Among Group 1, primary and secondary patency rates were 61% and 71%, respectively
      at 1 year with 15 complications, 3 infections, 8 thromboses, 2 aneurysms, 1
      homograft degradation, and 1 death related to surgery. Among Group 2, the primary
      and secondary patency rates were 71% and 79%, respectively, at 1 year with 6
      patients experiencing complications. Group 3 did not have complications with a
      primary patency rate of 67% at 1 year. CONCLUSIONS: The use of cryopreserved
      arterial homografts is a valid, accessible, and safe alternative in complicated
      vascular situations. In our country, it is a technology to consider for patients
      with critical limb ischemia, when the risk of a major amputation is high and it
      is not possible to have a suitable vein or prosthetic bypass. It can be an
      excellent alternative for the substitution of infected synthetic bypasses,
      especially to substitute in situ for an infected aortic graft.

PMID- 19857781
TI  - Renal transplantation program in Cuba.
AB  - Kidney transplantation has been performed in Cuba since 1970. In 1979, compatible
      living-related donors were introduced into our renal transplantation program.
      There are 43 hospitals distributed around the country with a multidisciplinary
      group that attends cadaveric donors with encephalic death. The donor rate in Cuba
      oscillates between 15 and 18 per million; 90% of them are from cadaveric donors.
      This program includes 47 dialysis centers throughout the country with 2300
      patients as supported by a National Coordinating Center at The Nephrology
      Institute. Cuba is one of the first countries in our region with this experience.

PMID- 19857782
TI  - Morbimortality in heart and lung transplantation in Cuba: a 20-year follow-up.
AB  - The first orthotopic heart transplantation (OHT) was performed in 1967 by C.N.
      Barnard in Cape Town, South Africa. The first OHT in Cuba was performed in 1985.
      The main purpose of our study was to determine some of the aspects related to the
      short-, mid-, and long-term morbimortality rates of OHT patients in Cuba. We
      analyzed the first 120 OHTs (3 heart plus lung transplantations, 4
      retransplantations, and 113 heart transplantations) which were performed in Cuba
      from December 1985 to December 2005. Based on the analysis, we performed a
      descriptive, retrospective research about morbimortality. There was a
      predominance of the masculine sex (5.31:1). The overall mean age was 45.13 +/-
      11.58 years (range, 14-67 years). The most frequent pretransplant diagnosis was
      coronary artery disease (CAD; n = 69; 57.5%). Analyzing the Kaplan-Meier survival
      curve, we observed that the survival probability at 1 year was 83.3%; at 5 years,
      45.7%; and at 10 years 19.2%. The complications by frequency were: sepsis (n =
      41; 37%), acute rejection episodes (n = 42; 35.0%), and neoplasia (n = 4; 3.3%).
      Complications in frequency order were sepsis and acute rejection episodes among
      short term and chronic rejection and chronic renal failure among long-term
      survivors.

PMID- 19857783
TI  - American College of Radiology appropriateness criteria on multiple brain
      metastases.

PMID- 19857784
TI  - Bevacizumab as therapy for radiation necrosis in four children with pontine
      gliomas.
AB  - PURPOSE: Diffuse pontine gliomas are a pediatric brain tumor that is fatal in
      nearly all patients. Given the poor prognosis for patients with this tumor, their
      quality of life is very important. Radiation therapy provides some palliation,
      but can result in radiation necrosis and associated neurologic decline. The
      typical treatment for this necrosis is steroid therapy. Although the steroids are
      effective, they have numerous side effects that can often significantly
      compromise quality of life. Bevacizumab, an antibody against vascular endothelial
      growth factor, has been suggested as a treatment for radiation necrosis. We
      report on our initial experience with bevacizumab therapy for radiation necrosis
      in pediatric pontine gliomas. MATERIALS AND METHODS: Four children with pontine
      gliomas treated at the Children's Hospital in Denver and the University of
      Colorado Denver developed evidence of radiation necrosis both clinically and on
      imaging. Those 4 children then received bevacizumab as a treatment for the
      radiation necrosis. We reviewed the clinical outcome and imaging findings.
      RESULTS: After bevacizumab therapy, 3 children had significant clinical
      improvement and were able to discontinue steroid use. One child continued to
      decline, and, in retrospect, had disease progression, not radiation necrosis. In
      all cases, bevacizumab was well tolerated. CONCLUSIONS: In children with pontine
      gliomas, bevacizumab may provide both therapeutic benefit and diagnostic
      information. More formal evaluation of bevacizumab in these children is needed.

PMID- 19857785
TI  - Radiation response of cancer stem-like cells from established human cell lines
      after sorting for surface markers.
AB  - PURPOSE: A subpopulation of cancer stem-like cells (CSLC) is hypothesized to
      exist in different cancer cell lines and to mediate radioresistance in solid
      tumors. METHODS AND MATERIALS: Cells were stained for CSLC markers and sorted
      (fluorescence-activated cell sorter/magnetic beads) to compare foci and
      radiosensitivity of phosphorylated histone H2AX at Ser 139 (gamma-H2AX) in sorted
      vs. unsorted populations in eight cell lines from different organs. CSLC
      properties were examined using anchorage-independent growth and levels of
      activated Notch1. Validation consisted of testing tumorigenicity and
      postirradiation enrichment of CSLC in xenograft tumors. RESULTS: The quantity of
      CSLC was generally in good agreement with primary tumors. CSLC from MDA-MB-231
      (breast) and Panc-1 and PSN-1 (both pancreatic) cells had fewer residual gamma
      H2AX foci than unsorted cells, pointing to radioresistance of CSLC. However, only
      MDA-MB-231 CSLC were more radioresistant than unsorted cells. Furthermore, MDA-MB
      231 CSLC showed enhanced anchorage-independent growth and overexpression of
      activated Notch1 protein. The expression of cancer stem cell surface markers in
      the MDA-MB-231 xenograft model was increased after exposure to fractionated
      radiation. In contrast to PSN-1 cells, a growth advantage for MDA-MB-231 CSLC
      xenograft tumors was found compared to tumors arising from unsorted cells.
      CONCLUSIONS: CSLC subpopulations showed no general radioresistant phenotype,
      despite the quantities of CSLC subpopulations shown to correspond relatively well
      in other reports. Likewise, CSLC characteristics were found in some but not all
      of the tested cell lines. The reported problems in testing for CSLC in cell lines
      may be overcome by additional techniques, beyond sorting for markers.

PMID- 19857787
TI  - Validation of temporal optimization effects for a single fraction of radiation in
      vitro.
AB  - PURPOSE: To experimentally validate how temporal modification of the applied dose
      pattern within a single fraction of radiation therapy affects cell survival.
      METHOD AND MATERIALS: Using the linear-quadratic model, we have previously
      demonstrated that the greatest difference in cell survival results from comparing
      a temporal dose pattern delivering the highest doses during the middle of a
      fraction and the lowest at the beginning and end ("Triangle") to one with the
      lowest doses at the middle and the highest at the beginning and end ("V-shaped").
      Also, these differences would be greatest in situations with low alpha/beta and
      large dose/fraction and fraction length. Two low (WiDr, PC-3) and one high (SQ
      20B) alpha/beta cell lines were irradiated in six-well plates with 900 cGy over
      20 min (900 cGy/20 min), one each with a Triangle and V-shaped dose pattern. WiDr
      cells were subjected to the same experiments with first 180 cGy/20 min, then 900
      cGy/5 min. Cell survival was assessed using the clonogenic assay. RESULTS: At 900
      cGy/20 min, irradiation with a V-shaped pattern resulted in an increased survival
      compared with use of a Triangle pattern of 21.2% for WiDr (p < 0.01), 18.6% for
      PC-3 (p < 0.025), and 4.7% for SQ-20B cells (p > 0.05). For WiDr cells at 180
      cGy/20 min, this increase reduced to 2.7% (p > 0.05) and to -0.8% (p > 0.05) at
      900 cGy/5 min. CONCLUSIONS: These results verify the assertions of the modeling
      study in vitro, and imply that the temporal pattern of applied dose should be
      considered in treatment planning and delivery.

PMID- 19857786
TI  - Identification of genes associated with progression and metastasis of advanced
      cervical cancers after radiotherapy by cDNA microarray analysis.
AB  - PURPOSE: To identify a set of genes related to the progression and metastasis of
      advanced cervical cancer after radiotherapy and to establish a predictive method.
      METHODS AND MATERIALS: A total of 28 patients with cervical cancer (15 stage
      IIIB, 13 stage IVA patients) who underwent definitive radiotherapy between May
      1995 and April 2001 were included in this study. All patients were positive for
      human papillomavirus infection and harbored the wild-type p53 gene. The
      expression profiles of 14 tumors with local failure and multiple distant
      metastasis and 14 tumors without metastasis (cancer free) obtained by punch
      biopsy were compared before treatment, using a cDNA microarray consisting of
      23,040 human genes. RESULTS: Sixty-three genes were selected on the basis of a
      clustering analysis, and the validity of these genes was confirmed using a cross
      validation test. The most accurate prediction was achieved for 63 genes
      (sensitivity, 78.8%; specificity, 38.1%). Some of these genes were already known
      to be associated with metastasis via chromosomal instability (TTK, BUB1B),
      extracellular matrix components (matrix metalloproteinase 1 [MMP-1]), and
      carcinogenesis (protein phosphatase 1 regulatory subunit 7 [PPP1R7]). A
      "predictive score" system was developed that could predict the probability for
      development of metastases using leave-one-out cross-validation methods.
      CONCLUSIONS: The present results may provide valuable information for identified
      predictive markers and novel therapeutic target molecules for progression and
      metastasis of advanced cervical cancer.

PMID- 19857788
TI  - Membrane-dependent bystander effect contributes to amplification of the response
      to alpha-particle irradiation in targeted and nontargeted cells.
AB  - PURPOSE: Free radicals are believed to play an active role in the bystander
      response. This study investigated their origin as well as their temporal and
      spatial impacts in the bystander effect. METHODS AND MATERIALS: We employed a
      precise alpha-particle microbeam to target a small fraction of subconfluent
      osteoblastic cells (MC3T3-E1). gammaH2AX-53BP1 foci, oxidative metabolism
      changes, and micronuclei induction in targeted and bystander cells were assessed.
      RESULTS: Cellular membranes and mitochondria were identified as two distinct
      reactive oxygen species producers. The global oxidative stress observed after
      irradiation was significantly attenuated after cells were treated with filipin,
      evidence for the primal role of membrane in the bystander effect. To determine
      the membrane's impact at a cellular level, micronuclei yield was measured when
      various fractions of the cell population were individually targeted while the
      dose per cell remained constant. Induction of micronuclei increased in bystander
      cells as well as in targeted cells and was attenuated by filipin treatment,
      demonstrating a role for bystander signals between irradiated cells in an
      autocrine/paracrine manner. CONCLUSIONS: A complex interaction of direct
      irradiation and bystander signals leads to a membrane-dependent amplification of
      cell responses that could influence therapeutic outcomes in tissues exposed to
      low doses or to environmental exposure.

PMID- 19857789
TI  - Strategies for online organ motion correction for intensity-modulated
      radiotherapy of prostate cancer: prostate, rectum, and bladder dose effects.
AB  - PURPOSE: To quantify and evaluate the accumulated prostate, rectum, and bladder
      dose for several strategies including rotational organ motion correction for
      intensity-modulated radiotherapy (IMRT) of prostate cancer using realistic organ
      motion data. METHODS AND MATERIALS: Repeat computed tomography (CT) scans of 19
      prostate patients were used. Per patient, two IMRT plans with different uniform
      margins were created. To quantify prostate and seminal vesicle motion, repeat CT
      clinical target volumes (CTVs) were matched onto the planning CTV using
      deformable registration. Four different strategies, from online setup to full
      motion correction, were simulated. Rotations were corrected for using gantry and
      collimator angle adjustments. Prostate, rectum, and bladder doses were
      accumulated for each patient, plan, and strategy. Minimum CTV dose (D(min)),
      rectum equivalent uniform dose (EUD, n = 0.13), and bladder surface receiving
      >or=78 Gy (S78), were calculated. RESULTS: With online CTV translation
      correction, a 7-mm margin was sufficient (i.e., D(min) >or= 95% of the prescribed
      dose for all patients). A 4-mm margin required additional rotational correction.
      Margin reduction lowered the rectum EUD(n = 0.13) by approximately 2.6 Gy, and
      the bladder S78 by approximately 1.9%. CONCLUSIONS: With online correction of
      both translations and rotations, a 4-mm margin was sufficient for 15 of 19
      patients, whereas the remaining four patients had an underdosed CTV volume <1%.
      Margin reduction combined with online corrections resulted in a similar or lower
      dose to the rectum and bladder. The more advanced the correction strategy, the
      better the planned and accumulated dose agreed.

PMID- 19857791
TI  - Radiation-induced sequelae measured by means of lymphocyte apoptosis: importance
      of certain single nucleotide polymorphisms: in regard to Schnarr et al. (Int J
      Radiat Oncol Biol Phys 2009).

PMID- 19857792
TI  - In reply to Dr. Lee: are prostate cancers created equal?

PMID- 19857794
TI  - EMS in Viracept--the course of events in 2007 and 2008 from the non-clinical
      safety point of view.
AB  - Viracept (nelfinavir) is an HIV protease inhibitor supplied by Roche outside the
      US, Canada and Japan. Viracept was first introduced by Roche in 1998. Although
      newer protease inhibitors have become available for the treatment of HIV, it is
      viewed as a useful medicine for patients who are intolerant to ritonavir (since
      it does not require ritonavir boosting), pregnant women, and patients in resource
      limited settings, since the formulation is heat-stable and does not require
      refrigeration. The relatively high prevalence of HIV in some of the third world
      countries means that it was also a product of choice for young women of
      childbearing age, pregnant and nursing women and young children. On 18 May 2007
      F. Hoffmann-La Roche received first reports of a "bad smell" of blisterpacked
      Viracept tablets and one adverse drug report of nausea and vomiting from patients
      in Spain. Subsequently, ethyl methanesulfonate (EMS), an established mutagen,
      carcinogen and teratogen was identified as the potential source of the bad smell.
      On 6 June 2007, Viracept was globally recalled as the extent of the contamination
      exceeded the guidances for permissible levels set by regulatory authorities by
      more than 1000-fold and hence human risk was not readily assessable. In the
      following, a compilation of the course of events from a non-clinical point of
      view is presented. This compilation only partially reflects the complexity of the
      case and the interactions between all parties between May/June 2007 and September
      2008 and hence necessarily remains partly a subjective compilation of the authors
      of this article. This compilation serves also as an introduction into this
      Special Issue of Toxicology Letters. The data on the cause and levels of
      contamination, likely duration of intake and affected patient population can be
      found in the subsequent contributions. Most importantly, we share in other parts
      of this Special Issue with the scientific community the data and risk assessment
      arguments that supported the conclusion by the company and regulatory authorities
      that the levels of contamination with EMS posed no health risk to affected
      patients.

PMID- 19857795
TI  - What happened: the chemistry side of the incident with EMS contamination in
      Viracept tablets.
AB  - A technical review of the events leading to the global recall of Viracept film
      coated tablets 250 mg in June 2007 is given from the drug substance manufacturing
      perspective. Root cause analysis performed and corrective actions implemented are
      presented. Using the decay rate of ethyl methane sulfonate in Viracept film
      coated tablets 250 mg at 25 degrees C derived from stability studies,
      establishing of the worst case scenario for patient exposure to ethyl methane
      sulfonate, is outlined. Whereas the first evaluation based on ethyl methane
      sulfonate levels found in the drug substance suggested a worst case patient
      exposure of 2300 ppm, the decay rate of ethyl methane sulfonate in the drug
      product and the time gap between drug product manufacture and earliest possible
      use by patients led to the conclusion that 920 ppm (+/-10%) over a period of
      approx. 90 days is a reasonably cautious assumption for the worst case patient
      exposure scenario.

PMID- 19857796
TI  - Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity
      of ethyl methanesulfonate.
AB  - In order to assess the risk of patients being exposed to an anti-AIDS medication
      contaminated with EMS we have performed in depth genotoxicity, general toxicity
      and DMPK investigations. The results of these studies are reported in the
      accompanying papers of this issue. Prior to starting our investigations we
      searched the literature for toxicity data on this well established mutagen with
      specific attention to dose-response relations in in vivo genotoxicity studies,
      since, obviously, in vivo data are pivotal for risk assessment. There are
      numerous published in vivo genotoxicity studies on EMS, with generally 50mg/kg -
      or higher - being the minimal dose used. The dose of 50mg/kg induced effects in
      some, but not all studies, while the dose of 100mg/kg was clearly positive in
      most studies, except for heritable mutations where a single dose of 100mg/kg was
      not observed to induce measurable effects in post-meiotic stages and even the
      maximal dose of 250 mg/kg was negative in pre-meiotic stages of male germ cell
      development. For somatic cells, NOEL values could not be derived for any of the
      endpoints studied. Although a large number of genotoxicity studies are available,
      none of the studies was sufficiently detailed to allow unambiguous conclusions
      about the presence of a (practical) threshold. But in most cases the dose
      responses show a sublinear relationship (i.e. the slope increases with dose)
      which indicates that the data would not be incompatible with a threshold dose
      response relationship. This stands in contrast to data on ethylnitrosourea (ENU)
      which has been studied concommittantly with EMS in several in vitro and in vivo
      genotoxicity investigations. ENU generally appeared to induce genotoxic effects
      with linear dose relationships. We also review the more limited data reported on
      teratogenicity and carcinogenicity of EMS. Induction of fetal malformations in
      mice appeared to have a NOEL of 100mg/kg. Classical life-time carcinogenicity
      studies have not been performed with EMS. Induction of mammary, lung, kidney,
      brain, and liver tumors has been observed after various short term treatment
      regimes. In none of the published studies a no effect level was reported and no
      exposure data are available. Overall, the experimental data do not fully
      characterize the carcinogenic potential of EMS and are insufficient for a risk
      extrapolation to humans. Although the data on teratogenicity and carcinogenicity
      are insufficient for assessing dose-response relations it is generally accepted
      that the genotoxic property of EMS is at the base of the teratogenic and
      carcinogenic effects.

PMID- 19857797
TI  - In vivo genotoxicity of EMS: statistical assessment of the dose response curves.
AB  - EMS induced micronuclei and lacZ mutations in in vivo studies in mice with a
      clearly sublinear dose dependency. As reported elsewhere in this issue, NOEL dose
      values of between 25 mg/kg/day and 80 mg/kg/day were observed for the different
      endpoints and tissues analysed. Here we show that statistical assessment of the
      data provides solid support that the induction of mutagenic and clastogenic
      effects after in vivo treatment with the directly DNA damaging mutagen EMS
      adheres to a thresholded dose response relation. These data corroborate similar
      evidence obtained in in vitro studies. We conclude that cells are fully capable
      of repairing large amounts of DNA ethylations induced by EMS without experiencing
      elevated mutation frequencies. The stochastic, linear risk assessment model
      generally employed for DNA damaging genotoxins can therefore be refuted for EMS.
      While presently this conclusion cannot be generalized to other genotoxins a
      change of paradigm appears to be indicated at least for alkylating agents
      inducing a comparable type and spectrum of DNA lesions as EMS.

PMID- 19857798
TI  - Considerations regarding a permitted daily exposure calculation for ethyl
      methanesulfonate.
AB  - Specification of human exposure limits to compounds with toxicities based on
      modes of action that allow considerations of a threshold and the safe estimation
      of a no-observed-effect level (NOEL) is normally based on acceptable daily intake
      (ADI) or permitted daily exposure (PDE) calculations using appropriate safety
      factors to account for differences between species, populations, length of
      observation and severity of lesions. In view of the reliable experimental
      evidence for a thresholded dose response of the genotoxicity of ethyl
      methanesulfonate (EMS) as reported in this special issue of Toxicology Letters
      such an acceptable daily intake proposal is made using the approach for setting
      permitted daily exposure limits outlined in appendix 3 of the ICH Q3C consensus
      guideline on residual solvents in pharmaceuticals (ICH, 2005). Up to now the
      specification of EMS exposure limits was based on the generic threshold of
      toxicological concern (TTC)-derived limit of 1.5mug/person/day as advocated by
      the CHMP [CHMP, 2006. Guideline on the limits of genotoxic impurities.
      www.emea.europa.eu/pdfs/human/swp/519902en.pdf (June 28, 2006) with Q&A
      www.emea.europa.eu/pdfs/human/swp/43199407en.pdf (June 25, 2008)] or on as low as
      technically achievable criteria. Such limits have been based on conservative
      linear dose-effect extrapolations corresponding to an excess cancer risk of 1 in
      100,000. We now present an EMS-specific PDE based on the reliable demonstration
      of a NOEL for induction of mutations in vivo of 25mg/kg/day. Using the most
      conservative safety factors described in ICH Q3C we derive a PDE of approximately
      100 microg/person/day using product safety factors still amounting to 12,000.

PMID- 19857799
TI  - The torch is passed again.

PMID- 19857800
TI  - Analysis of the mismatched manifestation between rCBF and rCBV maps in cerebral
      astrocytomas.
AB  - OBJECTIVE: To explore the mismatched manifestation between regional cerebral
      blood flow (rCBF) and regional cerebral blood volume (rCBV) of astrocytomas.
      METHODS: Both conventional and perfusion CT were performed on 29 patients with
      pathologically confirmed astrocytomas (15 cases in Grades I-II, 14 cases in
      Grades III-IV). Time-density curves were plotted, cerebral blood flow and volume
      maps were generated, and the values between rCBF and rCBV in the same region of
      interest (ROI) were compared. RESULTS: Twelve low-grade astrocytomas showed low
      or medium values of both rCBF (46.95+/-22.92 ml 100 g(-1) mm(-1)) and rCBV
      (5.74+/-3.61 ml 100 g(-1)); 12 high-grade astrocytomas showed high values of both
      rCBF (95.44+/-42.58 ml 100 g(-1) min(-1)) and rCBV (9.24+/-5.32 ml 100g(-1)).
      These cases exhibited agreement between the values of rCBF and rCBV. However, the
      remaining five astrocytomas were mismatched, showing reduced rCBF value and
      increased rCBV value in the same ROI. The discrepancy may mislead to an
      inaccuracy of perfusion CT in grading gliomas. CONCLUSIONS: The mismatched
      manifestation between rCBF and rCBV occasionally exists in some areas of
      astrocytomas. Hence, attention should be paid to assessments in preoperative
      grading of astrocytomas and in monitoring therapeutic effects.

PMID- 19857801
TI  - Saccular neck venous aneurysm on color duplex sonography: an analysis of 12
      cases.
AB  - OBJECTIVE: To discuss the characteristics of saccular neck venous aneurysm on
      color duplex sonography. METHODS: We retrospectively reviewed 12 cases of
      saccular neck venous aneurysm confirmed by either venogram or surgical pathology.
      Clinical information, physical exam of the neck, and characteristics of saccular
      neck venous aneurysm on color Doppler sonography (CDUS) were analyzed. Diagnosis
      and differential diagnosis of saccular venous aneurysm on color duplex sonography
      were discussed. RESULTS: The communication between saccular venous aneurysm and
      related vein was visualized on grayscale imaging in 11 cases (11/12), which was
      observed in all 12 cases (12/12) on color Doppler image. Spectral Doppler was
      useful in the demonstration of venous flow in both the communicating vein and
      venous aneurysm. The documentation of venous flow in both venous aneurismal sac
      and communicating vein was obviously improved with contrast enhanced ultrasound
      in one case. CONCLUSION: It is important to have knowledge of venous aneurysm, an
      uncommon condition in sonographic practice. Saccular venous aneurysm should be
      taken into consideration in differential diagnosis when a cystic lesion in the
      neck appears on color Doppler sonography.

PMID- 19857802
TI  - Computed tomography findings mimicking appendicitis as a manifestation of
      colorectal cancer.
AB  - The primary computed tomography (CT) signs of appendicitis can also be seen with
      other inflammatory or neoplastic processes. We report on two cases in which
      appendiceal dilatation and peri-appendiceal fluid or stranding were the dominant
      imaging manifestations of colorectal carcinoma in the ascending colon. This study
      highlights the need to closely examine the ascending colon in patients with a
      suspected CT diagnosis of acute appendicitis, since these findings may be
      secondary to an inconspicuous colorectal carcinoma.

PMID- 19857803
TI  - Contrast-enhanced CT colonography with 64-slice MDCT compared to endoscopic
      colonoscopy in the follow-up of patients after colorectal cancer resection.
AB  - BACKGROUND: Seventy percent of newly diagnosed colorectal cancer cases are
      potential candidates for curative surgery, but after resection, in 30%, the tumor
      will recur. Postoperative follow-up includes endoscopic colonoscopy (EC) and
      computed tomography (CT). There have been only a few publications on the use of
      contrast-enhanced CT colonography (CECTC) in the follow-up of these patients.
      METHODS: Twenty-nine consecutive patients after resection of colorectal cancer
      underwent CECTC and EC on the same day. CECTC studies were reviewed for
      identification of strictures, recurrence, polyps and metastases. RESULTS: The
      anastomosis was identified in 96% of patients on CECTC and in 82% on endoscopic
      colonoscopy. One stricture was identified by both techniques. One extraluminal
      recurrence was depicted only on CECTC. Sensitivity in detecting polyps was per
      polyp 93% and per patient 100%. CONCLUSION: CECTC performed on a 64-slice
      multidetector CT is reliable in imaging the postoperative colon for the follow-up
      of patients after resection of colorectal cancer.

PMID- 19857804
TI  - Comparison of different diagnostic methods for differentiating biliary atresia
      from idiopathic neonatal hepatitis.
AB  - AIM: To retrospectively analyze different methods in differentiating biliary
      atresia from idiopathic neonatal hepatitis. METHODS: Sixty-nine infants with
      cholestatic jaundice and final diagnosis of idiopathic neonatal hepatitis (INH)
      and biliary atresia (BA) were studied retroprospectively from January 2004 to
      December 2006. A thorough history and physical examination were undertaken. All
      cases underwent abdominal magnetic resonance cholangiography (MRCP),
      ultrasonography (US), hepatobiliary scintigraphy (HBS), HBS single-photon
      emission computer tomography (HBS SPECT), and operation or percutaneous liver
      biopsy. The accuracy, sensitivity, specificity, and predictive values of these
      various methods were compared. RESULTS: There were 39 girls and 30 boys, among
      whom 35 had INH (age, 61+/-17 days) and 34 had BA (age, 64+/-18 days). The mean
      age at onset of jaundice was significantly lower in cases of BA when compared to
      INH cases (9+/-13 vs. 20+/-21 days; P=.032). The diagnostic accuracy of different
      methods was as follows: liver biopsy, 97.1%; HBS SPECT, 91.30%; MRCP, 71.01%;
      HBS, 66.67%; US, 65.22%. CONCLUSION: Our results indicate that biopsy of the
      liver is considered as the most reliable method to differentiate INH from BA. The
      accuracy of HBS SPECT is higher than that of MRCP, HBS, and US. There was no
      significant difference in diagnostic accuracy among MRCP, HBS, and US.

PMID- 19857805
TI  - Perfusion study of liver lesions with superparamagnetic iron oxide:
      distinguishing hepatocellular carcinoma from focal nodular hyperplasia.
AB  - We performed a perfusion study with superparamagnetic iron oxide (SPIO) and
      evaluated the possibility of acquiring hemodynamic imaging in hypervascular
      hepatocellular nodules. Single-slice computed tomography during arteriography
      (SCTA) and an SPIO perfusion study were performed and compared. The findings of
      the direction of blood flow in the lesion and the findings corresponding to the
      corona enhancement on the SPIO perfusion study agreed well with the findings of
      SCTA. In conclusion, SPIO perfusion is useful in evaluating the hemodynamics of
      hypervascular hepatocellular nodules.

PMID- 19857806
TI  - The treatment of liver fibrosis induced by hepatocyte growth factor-directed,
      ultrasound-targeted microbubble destruction in rats.
AB  - OBJECTIVE: The purpose of this study was to explore the feasibility of using
      ultrasound-targeted microbubble destruction to treat liver fibrosis induced by
      hepatocyte growth factor (HGF). METHODS: Forty Wistar rats were divided into five
      groups after the models of liver fibrosis were prepared: (1) HGF, ultrasound, and
      microbubbles (HGF+US/MB); (2) HGF and ultrasound (HGF+US); (3) HGF and
      microbubbles (HGF+MB); (4) HGF (HGF); and (5) model alone (MA). All rats were
      killed after being transfected for 14 days. Recovery of the liver was detect by
      diffusion-weighted imaging (DWI) and pathological methods. Collagen I expression
      was detected by immunohistochemistry. Hepatocyte growth factor expression in the
      liver was detect by western blotting. RESULTS: The results of DWI and
      pathological examination showed the recovery of liver in HGF+US/MB group were
      better than those of other groups. In HGF+US/MB group, collagen I expression was
      less, and HGF protein was the highest among all the groups. CONCLUSIONS:
      Ultrasound-targeted microbubble destruction could deliver HGF into the fibrotic
      liver and produce an antifibrosis effect, which could provide a novel strategy
      for gene therapy of liver fibrosis.

PMID- 19857807
TI  - 18F-fluorodeoxyglucose uptake in uterine leiomyomas in healthy women.
AB  - The purpose of this study was to evaluate the incidence and features of increased
      FDG uptake in uterine leiomyomas in apparently healthy women. The incidence of
      increased FDG uptake is 0.1% in all 2193 women, 0.5% in women with uterine
      leiomyoma, and 3.4% in women with degenerated leiomyoma. There was no
      relationship between the intensity of FDG uptake and the size/site of leiomyoma
      or the tendency of degeneration in leiomyoma. The women with the increased uptake
      were not limited at premenopause.

PMID- 19857809
TI  - Coronary ostial involvement in acute aortic dissection: detection with 64-slice
      cardiac CT.
AB  - A 41-year-old man collapsed after lifting weights at a gym. Following admission
      to the emergency department, a 64-slice cardiac computed tomography (CT) revealed
      a Stanford Type A aortic dissection arising from a previous coarctation repair.
      Multiphasic reconstructions demonstrated an unstable, highly mobile aortic
      dissection flap that extended proximally to involve the right coronary artery
      ostium. Our case is an example of the application of electrocardiogram-gated
      cardiac CT in directly visualizing involvement of the coronary ostia in acute
      aortic dissection, which may influence surgical management.

PMID- 19857808
TI  - Flare phenomenon in positron emission tomography in a case of breast cancer--a
      pitfall of positron emission tomography imaging interpretation.
AB  - We present an unusual case of breast cancer with increased FDG uptake 4 months
      after chemotherapy. A PET-CT scan displayed results that mimicked multiple lymph
      node metastases in the right axilla, the mediastinum, and the bilateral pulmonary
      hilar regions. However, the increased FDG uptake disappeared 17 months later
      without any additional medical treatment, suggesting the occurrence of flare
      phenomenon.

PMID- 19857810
TI  - Life-threatening intra-abdominal hemorrhage from left superior colonic artery
      pseudoaneurysm after percutaneous renal biopsy: successful treatment with
      superselective arterial embolization.
AB  - Life-threatening intra-abdominal hemorrhage following ultrasonographically guided
      percutaneous renal biopsy is extremely rare and, most of the time, is due to
      renal vascular injury. Injury of other abdominal arteries during percutaneous
      renal biopsy is exceedingly rare. We report herein a case of left superior
      colonic artery injury during ultrasonographically guided percutaneous renal
      biopsy, which was responsible for pseudoaneurysm formation and subsequent intra
      abdominal hemorrhage and gastrointestinal bleeding. Arterial pseudoaneurysm was
      rapidly and successfully treated with minimally invasive endovascular treatment
      using microcoils. Superselective embolization stopped the bleeding and preserved
      colonic vascularization, thus preventing ischemia of the involved colonic
      segment.

PMID- 19857811
TI  - Sarcoidosis of the thoracic and lumbar vertebrae, mimicking metastasis or
      multifocal osteomyelitis by MRI: case report.
AB  - Sarcoidosis is a notoriously protean disease, but vertebral involvement is a rare
      entity. This is a case report of biopsy-proven thoracic and lumbar vertebral
      sarcoidosis in a 48-year-old Hispanic female with low back pain. Although this
      patient had normal plain films and computed tomography of the spine, her disease
      was first visualized by magnetic resonance imaging. The imaging findings were
      nonspecific, and the initial impression was hematopoietic malignancy vs
      disseminated infection.

PMID- 19857812
TI  - Leiomyosarcoma of the vagina: MR findings.
AB  - We report the magnetic resonance imaging findings of a case of vaginal
      leiomyosarcoma. The lesion was demonstrated as a well-defined heterogeneously
      hyperintense mass within the vagina on T2-weighted images and was demonstrated as
      a hypointense mass on T1-weighted images. The mass showed irregular enhancement
      on fat-suppressed T1-weighted images after administration of gadopentate
      dimeglumine. On pathological specimen, the nonenhancing foci of the mass were
      seen as the necrotic portion of the lesion.

PMID- 19857813
TI  - Sphaerodes mycoparasitica sp. nov., a new biotrophic mycoparasite on Fusarium
      avenaceum, F. graminearum and F. oxysporum.
AB  - A new species, Sphaerodes mycoparasitica (Ascomycetes, Melanosporales), was
      isolated from isolates of Fusarium avenaceum and Fusarium graminearum originating
      from wheat fields in Saskatchewan, and from Fusarium oxysporum originating from
      asparagus fields in Quebec, Canada. The species is characterized by a unique
      combination of ascospore size, shape (fusiform and triangular) and wall
      ornamentation (reticulate and smooth). Also, conidia are produced from simple
      phialides on the surface of ascoma peridial wall, on ascoma surrounding hyphae,
      and on irregularly branched conidiophores arising from hyphae. The closest
      relation of S. mycoparasitica is Sphaerodes quadrangularis, which has no detected
      anamorphic stage. The description of S. mycoparasitica, its phylogenetic position
      based on DNA sequences of large subunit ribosomal RNA gene (LSU)-as well as a key
      for all known Sphaerodes species are provided.

PMID- 19857814
TI  - A time of great change--and a time of great opportunity.

PMID- 19857815
TI  - Ankle valgus and subtalar varus in treated clubfoot.
AB  - The purpose of this study was to clarify whether residual subtalar varus in
      treated clubfoot affects the configuration of the ankle joint in the coronal
      plane. Radiographic characteristics of the ankle and subtalar joint in congenital
      clubfoot, after a minimum of 10 years of treatment, were analyzed and presented.
      Weight-bearing radiographs of the ankles and feet, as well as computerized
      tomographic images of the hindfoot, were obtained for 30 patients (41 feet), at a
      mean of 15.2 +/- 6.1 years after initial treatment. Subtalar varus was measured
      in terms of the tilting angle of the posterior facet of the talocalcaneal joint,
      as viewed using computerized tomographic scans, and a larger angle was indicative
      of greater subtalar varus. Ankle valgus was measured with anteroposterior mortise
      views; a larger angle was indicative of greater ankle valgus. The analyses showed
      that feet with greater subtalar varus also showed statistically significantly
      greater valgus of the ankle mortise angles (P = .003). These results suggest that
      the ankle compensates for residual deformity of the subtalar joint in the coronal
      plane in patients treated for clubfoot. It also suggests that the configuration
      of the ankle during the course of treatment may warrant closer attention. LEVEL
      OF CLINICAL EVIDENCE: 2.

PMID- 19857816
TI  - Transosseous fixation of the distal tibiofibular syndesmosis: comparison of an
      interosseous suture and endobutton to traditional screw fixation in 50 cases.
AB  - In this prospective cohort study, we compared screw fixation to interosseous
      suture with endobutton repair of the syndesmosis. Outcomes of interest included
      preoperative and postoperative modified American Orthopedic Foot and Ankle
      Society (AOFAS) hindfoot and ankle scores, and Short Form-12 health status
      scores, as well as radiographic measurements and the time to full weight bearing.
      Mean averages and ranges were calculated for numeric variables, and outcomes for
      each fixation group were compared statistically with Student t test. The cohort
      consisted of 50 patients; 25 in the screw fixation group and 25 in the
      interosseous wire with endobuttons group. The mean patient age was 34.68 (15 to
      55) years in the interosseous suture endobutton group and 36.68 (17 to 74) years
      in the screw group, and the mean follow-up was 10.78 (range 6 to 12) months in
      the interosseous suture endobutton group, and 8.20 (range 4 to 24) months in the
      screw group. No statistically significant differences (P < or = .05) were noted
      in regard to age, follow-up duration, time to postoperative weight bearing, or
      subjective outcome scores between the fixation groups; although statistically
      significant improvements were noted in the subjective scores for each fixation
      group between the preoperative and postoperative measurements. The results of
      this study indicate that the interosseous suture with endobuttons is a reasonable
      option for repair of ankle syndesmotic injuries, and may be as effective as
      traditional internal screw fixation. LEVEL OF CLINICAL EVIDENCE: 2.

PMID- 19857817
TI  - Can persistent drop foot after calf muscle lengthening be predicted
      preoperatively?
AB  - Calf muscle lengthening usually corrects equinus gait satisfactorily in stance.
      While in swing, the foot remains in drop foot in approximately half the limbs.
      The aim of this study was to evaluate if any preoperative clinical findings or
      kinematic and kinetic data could predict the outcome regarding drop foot. The
      study included 34 children with cerebral palsy. The average age was 9.3 years.
      Only children with preoperative maximum ankle dorsiflexion in stance and maximum
      ankle dorsiflexion in swing more than 2 standard deviations below the normal mean
      were included. The children underwent preoperative and postoperative clinical
      examination and gait analysis. Forty calf muscle lengthenings were performed (26
      tendo-achilles lengthenings, 14 gastrocnemius recessions). Nineteen of 40 limbs
      remained in drop foot despite satisfactory correction in stance. There was a
      significant association between postoperative drop foot and increased
      preoperative maximum plantar flexion in initial swing (P = .004; odds ratio,
      0.906). A limited number of tests of preoperative selective motor control of
      dorsiflexion of the ankle indicated that normal function is strongly indicative
      of postoperative normal swing phase. There were no significant associations
      between postoperative drop foot and preoperative clinical findings, gait
      function, type of gait pattern, type of cerebral palsy, and type of operation.
      Preoperative maximum plantar flexion in an initial swing of less than -42 degrees
      and a preoperative normal selective motor control of dorsiflexion of the ankle
      are strongly indicative of postoperative normal swing phase. A lower selective
      motor control score rather than normal function is not predictive of either
      normal swing or drop foot. LEVEL OF EVIDENCE: 2.

PMID- 19857818
TI  - A modified Jones procedure for managing clawing of lesser toes in pes cavus: long
      term follow-up in 8 patients.
AB  - Pes cavus is a complex foot deformity in which surgical correction remains
      challenging. We treated lesser-toe clawing in 11 feet of 8 patients (5 women, 1
      bilateral; 3 men, 2 bilateral) with a modified Jones procedure and assessed long
      term functional outcomes. We reviewed case notes and completed the Bristol Foot
      Score, the modified American Orthopaedic Foot & Ankle Society Midfoot Score, and
      a patient satisfaction questionnaire by means of telephone interviews. Mean age
      of the patients at the time of surgery was 30 years (range, 10-58 years). Mean
      time from surgery to the last clinical follow-up was 7 years (range, 0.5-17
      years), and mean time from surgery to the telephone interview was 9 years (range,
      1-18 years). At the final clinical review, all 11 feet were improved, although 6
      had minor complications. The mean Bristol Foot Score was 27 (range, 16-55), and
      the mean modified American Orthopaedic Foot & Ankle Society Midfoot Score was 76
      (range, 47-90), indicative of excellent results. Half of the patients had mild
      persistent foot pain, but all were satisfied with the outcome. Based on our
      experience with this group of patients, the modified Jones procedure yields
      satisfactory correction of lesser toe clawing in patients with flexible pes
      cavus. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857819
TI  - A retrospective analysis of 22 patients treated with percutaneous radiofrequency
      nerve ablation for prolonged moderate to severe heel pain associated with plantar
      fasciitis.
AB  - A retrospective study involving 22 patients (31 feet) with a history of prolonged
      moderate to severe heel pain associated with plantar fasciitis were examined to
      determine if ablation of the sensory branch of the medial calcaneal nerve would
      result in symptomatic relief. Participants in this study were given subjective
      questionnaires and visual analog scales in order to rate their symptoms before
      and after nerve ablation using radiofrequency energy. The results showed that the
      mean preintervention visual analog pain score was 8.12 +/- 1.61 (with 10 being
      the worst pain the patient could imagine), and this dropped to 3.26 +/- 1.97
      after 1 week and 1.46 +/- 1.76 after 1 month, 1.96 +/- 1.98 at 3 months, and 2.07
      +/- 2.06 at 6 months, and the improvement was statistically significant (P <
      .001) at each stage of follow-up. Furthermore, patients followed for up to 1 year
      showed no significant worsening of symptoms. Adverse events were limited to
      hematoma at the site of entry of the radiofrequency cannula. These findings
      support the conclusion that radiofrequency nerve ablation be considered an
      alternative to repetitive corticosteroid injections or open surgical intervention
      for the treatment of recalcitrant plantar heel pain. LEVEL OF CLINICAL EVIDENCE:
      4.

PMID- 19857820
TI  - Is there histomorphological evidence of plantar metatarsal fat pad atrophy in
      patients with diabetes?
AB  - The etiology of diabetic foot ulceration remains incompletely understood. Among
      other factors such as foot deformity in the presence of neuropathy, plantar fat
      pad atrophy has been identified as a contributory factor in diabetic foot
      ulceration. An association between fat pad atrophy and diabetic foot ulceration
      has been documented by imaging and histomorphological analysis of the calcaneal
      fat pad. However, histomorphological analysis of the metatarsal fat pad has not
      been performed to date. The present study entailed 14 patients with diabetes and
      14 nondiabetic controls and was aimed at documenting histomorphological evidence
      for presumed plantar metatarsal fat pad atrophy in patients with diabetes.
      Histological stains and computer-assisted planimetry were performed on samples of
      metatarsal fat obtained during forefoot surgery. The histomorphological and
      planimetric analyses of adipocyte cross-sectional area and nuclear density
      demonstrated no differences between patients with diabetes and control patients.
      Our findings demonstrate that systemic atrophy of the metatarsal fat pad is not
      present in the diabetic foot and may not explain the structural changes
      previously proposed by noninvasive imaging. LEVEL OF CLINICAL EVIDENCE: 3.

PMID- 19857821
TI  - Arthrodesis of the first metatarsophalangeal joint using a single screw:
      retrospective analysis of 109 feet.
AB  - Arthrodesis of the first metatarsophalangeal joint is a recommended technique for
      hallux rigidus. The preparation of the joint surfaces and the way in which
      fixation is achieved might be relevant in success or failure of the arthrodesis.
      All patients were selected from archived records of operations performed at the
      'Groene Hart' Hospital in Gouda, the Netherlands, from 1996 until 2005. Patients
      were operated following a fixed protocol using flat surfaces and a single
      compression screw bridging the arthrodesis from proximal medial to distal
      lateral. Their charts were reviewed retrospectively. Answers to questions
      regarding their current pain, shoe wear, and walking ability were recorded using
      the criteria of the AOFAS foot score as a template in a questionnaire. Of a total
      of 109 arthrodesis, 104 (95.4 %) united within 8 weeks without problems. Four
      feet were re-operated for pseudoarthrosis and one was re-operated for malunion
      with too much dorsiflexion. Removal of the intramedullary screw was necessary in
      85 feet (78%). Of the 79 patients who returned their questionnaire, 58 patients
      (73.4%) considered their problems solved and 57 patients (72%) were completely
      satisfied with the result. Our study shows that a single screw fixation method is
      an effective technique in treating hallux rigidus, with high satisfaction in
      patients between 40 and 80 years of age. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857822
TI  - The opening base wedge osteotomy and subsequent lengthening of the first
      metatarsal: an in vitro study.
AB  - Traditionally, the opening base wedge osteotomy has been indicated in a moderate
      to severe hallux abducto valgus deformity with a short first metatarsal. This in
      vitro study aimed to address the question of how much lengthening is inherent to
      the geometric design of an opening wedge in the first metatarsal. The
      preosteotomy length of a first metatarsal segment was compared with postosteotomy
      length after performing transverse and oblique basilar osteotomies while
      maintaining the opening wedge with a prefabricated spacer. In the current bench
      study, it was found that the opening base wedge osteotomy does indeed lengthen
      the first metatarsal, albeit a small percentage of the total length (1%-2.8%),
      and there was no significant difference between the lengths achieved through a
      transverse or oblique osteotomy based on a confidence interval of 95%. LEVEL OF
      CLINICAL EVIDENCE: 5.

PMID- 19857823
TI  - Complications associated with autogenous bone marrow aspirate harvest from the
      lower extremity: an observational cohort study.
AB  - The purpose of this article is to report the complications associated with
      autogenous bone marrow aspirate harvested from the lower extremity (ie, tibia
      and/or calcaneus) for soft tissue and/or osseous healing augmentation. This is a
      multisite, multisurgeon, observational cohort study involving retrospective
      review of prospectively collected data of 548 autogenous bone marrow aspirate
      harvests from the lower extremity of 530 consecutive patients between August 2000
      and March 2009. Each patient underwent autogenous bone marrow aspirate harvest
      from the proximal medial tibial metaphysis, distal medial tibial metaphysis,
      medial malleolus, lateral calcaneus, medial calcaneus, or a combination of both
      the proximal tibial metaphysis and lateral calcaneus for application to split
      thickness skin graft application sites or for mixture with allogeneic bone graft
      material for osseous defects or arthrodesis. Patients were kept non-weight
      bearing based on the index procedure and followed until clinical healing occurred
      or failure was declared. There were 324 female and 206 male patients with a mean
      age of 54.7 +/- 14.1 years (range: 14 to 84 years). There were 276 left
      feet/ankles and 272 right feet/ankles undergoing operative interventions with 18
      harvests occurring from the proximal medial tibial metaphysis, 183 from the
      distal medial tibial metaphysis, 11 from the medial malleolus, 325 from the
      lateral calcaneus, 3 from the medial calcaneus, and 8 from both the proximal
      tibial metaphysis and lateral calcaneus. All procedures were deemed successful
      with no nerve-related injury, infection, wound-healing complications, or
      iatrogenic fracture occurring. When properly performed, autogenous bone marrow
      aspirate harvest from various locations about the lower extremity as described
      here represent safe and minimally invasive techniques useful for soft tissue and
      osseous healing augmentation. LEVEL OF EVIDENCE: 4 (Case Series; Therapeutic
      Study).

PMID- 19857824
TI  - Pseudomonas osteomyelitis of the talus: review of the pathophysiology and report
      of a rare case.
AB  - Hematogenous Pseudomonas aeruginosa osteomyelitis of the talus is a rare cause of
      ankle swelling and limping in children. The case presented herein is that of
      chronic osteomyelitis of the talus with sequestrum formation. The patient was
      successfully treated with sequestrectomy and curettage, immobilization, and
      antibiotic therapy. One year following the operation, the patient displayed mild
      restriction of ankle dorsiflexion, without evidence of inflammation or arthritis,
      and radiographs revealed remodeling of the talar neck with increased radiographic
      density at the site of sequestrectomy. There was no evidence of avascular
      necrosis or disturbance of the growth of the talus. Although rare, osteomyelitis
      of the talus should be considered in children and adolescents who present with
      ankle swelling and an antalgic gait. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857825
TI  - Chopart's amputation for resection of clear cell sarcoma of the foot: a case
      report and review of the literature.
AB  - Clear cell sarcoma (CCS) is a subset of soft tissue sarcoma that occurs mainly in
      young Caucasians. Although on initial presentation these growths might not appear
      to be malignant, CCS has a tendency to disseminate to regional lymph nodes and
      ultimately develop distant metastasis. We report a case of CCS from our
      institution, discussing the radiological and pathological findings, surgical
      treatments, and survival prognoses. To our knowledge, this is the first reported
      case of using a Chopart's amputation technique in the resection of CCS of the
      foot. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857826
TI  - Percutaneous flexor tenotomy for treatment of neuropathic toe ulceration
      secondary to toe contracture in persons with diabetes: a systematic review.
AB  - Percutaneous flexor tenotomy has been proposed for treatment of neuropathic toe
      ulcerations secondary to toe contracture in persons with diabetes who have failed
      ongoing local wound care measures due to the perceived safety and efficacy.
      Because this patient population comprises a substantial proportion of the
      authors' practice, we undertook a systematic review of electronic databases and
      other relevant sources to identify material relating to the use of percutaneous
      flexor tenotomy for the treatment of neuropathic toe ulcerations secondary to toe
      contracture deformities in persons with diabetes. Information from peer-reviewed
      journals, as well as that from non-peer-reviewed publications, abstracts and
      posters, textbooks, and unpublished works, was considered. In an effort to
      procure the highest-quality studies available, studies were eligible for
      inclusion only if they involved consecutively enrolled patients undergoing the
      same percutaneous surgical treatment, evaluated patients at a mean follow-up of >
      or =12 months' duration, and included details of complications. Two studies were
      identified that met the inclusion criteria, both of which were retrospective case
      series of relatively poor methodological quality. Rather than providing strong
      evidence for or against the use of percutaneous flexor tenotomy for the treatment
      of neuropathic toe ulceration secondary to toe contracture in persons with
      diabetes, the results of this systematic review make clear the need for
      methodologically sound prospective cohort studies and randomized controlled
      trials that focus on the use of this form of surgical intervention. LEVEL OF
      EVIDENCE: 1.

PMID- 19857827
TI  - The dot-in-circle sign in Madura foot.
AB  - The literature states that proper management of Madura foot strongly depends on
      accurate identification of the causative organism. We describe the case of a
      patient with Madura foot who was diagnosed with eumycetoma after the dot-in
      circle sign, which has been previously reported in regard to magnetic resonance
      images of this lesion, was observed on both ultrasound and magnetic resonance
      images. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857828
TI  - Surgical management of closed tibiotalar dislocation: a case report and 2-year
      follow-up.
AB  - We report a case of a closed tibiotalar dislocation without an associated
      malleolar fracture, in the presence of medial malleolar hypoplasia, treated with
      closed reduction and surgical repair of the deltoid ligament, followed by cast
      immobilization. Post-reduction radiographs, before open repair of the deltoid
      ligament, revealed an Elise test ratio of 0.43. The ruptured superficial and deep
      portions of the deltoid ligament and the anterior ankle capsule were primarily
      repaired with suture, after which cast immobilization and non-weight bearing were
      used before physiotherapy and rehabilitation. Two years after the injury, the
      patient was pain free with a full range of ankle motion, and there were no signs
      of residual instability or early osteoarthritis. Subjective clinical testing
      using a valid health measurement instrument revealed an excellent clinical
      outcome. Based on our experience in this case, closed ankle dislocation in the
      presence of a hypoplastic medial malleolus and stress manipulation evidence of
      medial instability indicates the need for primary repair of the deltoid ligament.
      LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857829
TI  - Total talar extrusion: a case report.
AB  - Total talar extrusion is an extremely rare injury that occurs after a high-energy
      trauma. There are few reported cases in literature and there is no consensus as
      to the appropriate treatment of the extruded talus. Historically, the treatment
      options for open total talar dislocation have been limited to talectomy and
      fusion or reimplantation after thorough debridement. We report a case of an open
      dislocation of the talus with total talar extrusion. Immediate surgical
      debridement, reduction, and external fixation were performed under antibiotic
      coverage. Antibiotic-impregnated polymethylmethacrylate beads were implanted and
      the wound underwent a second debridement and delayed primary closure at 48 hours
      post injury. The patient remained in an external fixator for 6 weeks. She was
      subsequently placed in a cast and remained non-weight bearing for an additional 6
      weeks. Her wound healed uneventfully and she was permitted to begin progressive
      weight bearing at 12 weeks. The patient did not develop an infection or avascular
      necrosis. Literature cites infection and avascular necrosis as the main
      complications associated with a talar extrusion. Good open fracture protocol can
      reduce the risk of infection. Reduction of the extruded talus is preferable to
      preserve function and maintain normal hindfoot anatomy. Talectomy should be
      reserved as a salvage procedure. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857830
TI  - Bizarre parosteal osteochondromatous proliferation of the metatarsal: a pediatric
      case report and archival review.
AB  - Bizarre parosteal osteochondromatous proliferations (BPOP), also known as Nora's
      lesions, are rare tumors occurring most commonly in the hands and feet. They are
      benign and rarely exhibit radiological evidence of cortical invasion. We report a
      case of BPOP showing atypical magnetic resonance imaging features that are
      inconsistent with BPOP and having a novel chromosomal aberration. We also review
      the BPOP cases in our regional benign bone tumor database. LEVEL OF CLINICAL
      EVIDENCE: 4.

PMID- 19857831
TI  - Application of a fasciocutaneous free flap for treatment of a severe soft tissue
      injury of the foot and ankle: a case report.
AB  - The authors report an unusual case wherein a fasciocutaneous free flap from an
      amputated upper limb was used to repair a severe soft tissue injury of the
      ipsilateral forefoot and ankle. After amputating the nonviable portions of the
      forefoot, a residual limb flap from the patient's forearm, pedicled with the
      brachial artery, was used to cover the lower extremity defect. Three years after
      the injury, the patient was able to maintain balance and ambulate without
      assistance on the reconstructed lower extremity. LEVEL OF CLINICAL EVIDENCE: 4.

PMID- 19857832
TI  - Vessel loop closure technique in open fractures and other complex wounds in the
      foot and ankle.
AB  - A gaping wound of the foot and ankle can be difficult to close. In cases in which
      wound margin mobility is suitable, the use of a vessel loop, or loops, to provide
      sufficient tension for wound margin reapproximation can be a useful adjunct to
      the surgical management of wounds that would otherwise be very difficult to close
      without the use of a skin graft or flap coverage. In this report, we describe the
      use of a vessel loop, or loops, for reapproximation of the margins of gaping
      wounds of the foot or ankle.

PMID- 19857834
TI  - Foreword.

PMID- 19857833
TI  - An anatomic and autologous lateral ankle stabilization.
AB  - A new technique for stabilization of the lateral ankle ligaments is presented.
      The procedure uses a split peroneus longus tendon to recreate the calcaneofibular
      and anterior talofibular ligaments. The new ligaments follow a precise anatomic
      course that replicates the pathway of the original ligaments. The procedure also
      capitalizes on interference screw technology so that accurate ligament tension
      can be obtained. This technique is most useful for severe ligamentous
      insufficiency involving both the calcaneofibular and anterior talofibular
      ligaments. Biomechanical rationale for the use of peroneus longus is also
      discussed.

PMID- 19857835
TI  - Preface.

PMID- 19857836
TI  - Anatomy and biomechanical aspects of the gastrocsoleus complex.
AB  - The complexity of its anatomy coupled with the biomechanics of the Achilles
      tendon may explain the frequency of injury to this structure. Its unique
      characteristic of the muscle crossing three joints (knee, ankle, and subtalar
      joints) makes it more susceptible to injury than muscles that span a single
      joint. A better understanding of the contributing pathologic conditions
      associated with functional shortening of the gastroc-soleus complex and its
      effects on the normal biomechanics of the foot and ankle may improve the
      treatment of the many and varied pathologies that occur within the tendon itself
      and the associated abnormalities that occur with a tight Achilles tendon.

PMID- 19857837
TI  - Achilles lengthening procedures.
AB  - Contracture of the gastrocnemius-soleus complex with equinus deformity is a
      common hindfoot condition. In children, it is frequently associated with
      neuromuscular conditions such as cerebral palsy. In the adult population, it is
      linked to numerous pathologies such as adult-acquired flatfoot, diabetic
      neuropathic ulcers, and plantar fasciitis. With the medial column reduced,
      failure to achieve 10 degrees of passive ankle dorsiflexion with the knee flexed
      and extended suggests a contracture. This article reviews the anatomical and
      evolutionary basis for human foot structure, implications of tight gastrocnemius,
      and specific disease states. Operative releases for lengthening, including
      proximal gastrocnemius recession, tendo-Achilles lengthening, and endoscopic
      recession, are detailed.

PMID- 19857838
TI  - Insertional Achilles tendinosis: pathogenesis and treatment.
AB  - Insertional Achilles tendinopathy can be a painful debilitating condition that
      should initially be treated non-operatively. If pain becomes chronic and
      debilitating, despite appropriate conservative treatment, debridement of the
      diseased portion of the Achilles tendon and removal of the impinging calcaneal
      prominence and transfer of the flexor hallucis longus through a single incision
      can be a reliable pain relieving procedure with relatively high patient
      satisfaction.

PMID- 19857839
TI  - Surgical treatment of non-insertional Achilles tendinitis.
AB  - Noninsertional Achilles tendinitis is a distinct clinical entity, frequently
      characterized by swelling, pain, and lower limb dysfunction. This condition can
      be frustrating to treat, for the patient and the physician alike, as reflected in
      the various treatments, both conservative and surgical, that have been described.
      Although many patients with Achilles tendinitis can be successfully treated with
      nonoperative methods, persistent symptoms require surgical treatment, such as
      tenotomy, debridement, or repair.

PMID- 19857840
TI  - Conservative treatment of Achilles tendinopathy: emerging techniques.
AB  - Achilles tendinopathy is a painful condition that occurs commonly in both active
      and inactive individuals. It seems that this condition is painful as a result of
      ingrowth of neural structures and neovessels leading to poor healing, rather than
      from inflammatory mediators. Traditional conservative measures are often
      successful. There is a subset of patients who fail to respond to these measures,
      however, and this has led to the investigation of newer conservative techniques.
      This article provides a review of many of the emerging techniques in the
      treatment of Achilles tendinopathy.

PMID- 19857841
TI  - Non-surgical management of Achilles ruptures.
AB  - Incidence of Achilles tendon injury has increased as people continue to be active
      in their later years. Although acute rupture of the Achilles tendon is most
      commonly diagnosed using history and physical examination, improvements in
      magnetic resonance and ultrasound imaging have led to their routine use in
      evaluating these injuries. Non-operative versus operative management of acute
      Achilles tendon ruptures has been the subject of much controversy in the current
      literature, especially in light of non-operative treatment with functional
      bracing. This article highlights the current controversy and outlines the
      rationale for nonsurgical treatment of acute Achilles tendon ruptures.

PMID- 19857842
TI  - Minimal incision techniques for acute Achilles repair.
AB  - This article reviews minimal incision techniques in the treatment of acutely
      ruptured Achilles tendon and the results that can be anticipated from these
      methods. However, lack of robust prospective randomized studies on the treatment
      of Achilles tendon rupture makes it impossible to draw conclusions on optimal
      treatment strategies. The bulk of the evidence available suggests that surgical
      repair reduces rerupture rates compared with non-operatively treated tendon
      ruptures. Surgery does have potential complications, but as outlined in the
      article, using a mini-open or percutaneous technique of repair might result in
      highly satisfactory outcomes with acceptably low complication rates.

PMID- 19857843
TI  - Open repair of acute Achilles tendon ruptures.
AB  - Although the Achilles tendon is the strongest in the body, it also is the most
      often ruptured. Achilles tendon rupture most often occurs during sports
      activities in middle-aged men. Operative repair of a ruptured Achilles tendon can
      be accomplished with a variety of techniques, ranging from open repair, to
      minimally invasive technique, to endoscopic-assisted repair. This article focuses
      on open repair of acute Achilles tendon rupture. Surgical techniques,
      rehabilitation protocol, and the authors' preferred method are described.

PMID- 19857844
TI  - Chronic Achilles tendon ruptures.
AB  - Chronic Achilles ruptures present a significant challenge for the treating
      physician. These patients often have marked impairment of functional activities
      and usually require surgical treatment to optimize outcome. This article reviews
      some of the methods that have been described to treat the chronic or neglected
      Achilles tendon rupture. The methods that have been used include gastrocnemius
      advancement, fascial turndown flaps, local tendon transfers, free tissue
      transfer, and use of synthetic grafts. There are no comparative data to guide
      evidence-based decision making in regard to choosing between treatment options.

PMID- 19857845
TI  - Tendon transfers for Achilles reconstruction.
AB  - Tendon transfers are commonly used in the foot and ankle to restore function in
      neglected ruptures, reconstruct degenerated tendons, and correct deformity. The
      Achilles tendon is commonly afflicted by these problems because of the dominant
      role it plays in the mechanics of gait and running and its inherently poor blood
      supply. This article discusses the general principles of tendon transfers with
      regard to Achilles tendon function, the surgical techniques involved, and
      published results using these techniques. The goal is to provide the orthopedic
      foot and ankle surgeon with a wide variety of techniques to solve both the
      straightforward Achilles tendon problem as well as the difficult revision case.

PMID- 19857846
TI  - Complications of the treatment of Achilles tendon ruptures.
AB  - Since the first reports in the medical literature of treatment of the Achilles
      tendon, complications have been recognized from both non-operative and operative
      techniques. These include tendon rerupture, sural nerve morbidity, wound healing
      problems, changes in tendon morphology, venous thromboembolism, elongation of the
      tendon, complex regional pain syndrome, and compartment syndrome. This article
      delineates the incidence for each of these complications, with differing
      techniques, methods of avoiding these complications and treatment methods if they
      occur.

PMID- 19857847
TI  - Posterior calf injury.
AB  - Acute injuries of the Achilles tendon are common among athletes and non-athletes
      alike. Injuries of other posterior calf muscles are far less common but should be
      considered in the differential, to ensure proper diagnosis and treatment of
      patients with calf injuries. This article focuses on these calf injuries,
      including injuries of the gastrocnemius, plantaris, soleus, and flexor hallucis
      longus, which may occasionally be mistaken for Achilles tendon disorders.

PMID- 19857848
TI  - Achilles tendon rehabilitation.
AB  - The operative management of acute Achilles tendon rupture marks the beginning of
      a comprehensive rehabilitation program. The goals of the rehabilitation program
      start with the reduction of pain and swelling and the recovery of ankle motion
      and power. They conclude with the restoration of coordinated activity and safe
      return to athletic activity. The rehabilitation protocol is directed by the
      injury and the quality of the repair, along with the patient's age, medical and
      social history, and athletic inclination. The protocol is dynamic and responsive
      to changing clinical findings.

PMID- 19857849
TI  - Abstracts of EPNS 2009 - 8th Congress of the European Paediatric Neurology
      Society. Harrogate, United Kingdom. September 30-October 3, 2009.

PMID- 19857851
TI  - Brachycephalia--a bastardisation of what makes cats special.

PMID- 19857853
TI  - Environmental enrichment: practical strategies for improving feline welfare.
AB  - PRACTICAL RELEVANCE: The clinical application of evidence-based enrichment
      strategies for the domestic cat housed in a variety of confined environments,
      ranging from the veterinary cage to the domestic home, is of particular
      importance - both in relation to providing opportunity for appropriate feline
      behaviour, and in the prevention and treatment of behavioural and associated
      health problems (eg, feline lower urinary tract disease associated with negative
      emotional states such as generalised anxiety). Environmental enrichment has
      gained particular relevance in the light of current animal welfare legislation.
      For example, in the UK, the Animal Welfare Act 2006 stipulates that
      owners/keepers have a duty of care to their animal(s) that includes allowing the
      animal to exhibit normal behaviour patterns. EVIDENCE BASE: Research into
      environmental enrichment as a means of improving animal welfare is still very
      much in its infancy, particularly in relation to the domestic cat. Thus, evidence
      based studies are somewhat sparse and more are needed to validate current
      recommended enrichment practices. AUDIENCE: This article aims to assist general
      veterinary practitioners to recognise how cats respond to confinement, and to
      understand what constitutes environmental enrichment, to help them implement or
      advise on appropriate enrichment strategies for cats confined in a hospital cage,
      home environment (particularly an indoor-only home), or cattery or rescue
      shelter, based on published evidence to date.

PMID- 19857852
TI  - Brachycephalic feline noses: CT and anatomical study of the relationship between
      head conformation and the nasolacrimal drainage system.
AB  - AIMS: A study was designed to evaluate the influence of head conformation on the
      course of the nasolacrimal drainage system (NDS) in 31 brachycephalic and 15
      mesocephalic cats using computed tomography (CT), CT-dacryocystography and
      anatomical methods. FINDINGS: The higher the degree of brachycephalia, the more
      the facial bones and upper canine teeth are displaced dorsally (ie, the more
      pronounced the dorsorotation). Dorsorotation leads to abnormal dislocation of the
      ventral nasal concha and to almost horizontally rotated upper canine teeth, and
      thus a steeply oriented NDS. In severe brachycephalia the NDS is forced to pass
      below the canine tooth (adopt a V-shaped course) and the drainage function seems
      to be inefficient. PRACTICAL RELEVANCE: The rotation of the upper canine teeth
      appears to provide a basis for classification of brachycephalia in cats. The
      authors recommend that breeders avoid breeding from individuals affected by this
      condition and to give preference to cats with longer facial bones.

PMID- 19857854
TI  - Treatment options for hyperphosphatemia in feline CKD: what's out there?
AB  - PRACTICAL RELEVANCE: Phosphorus is retained in chronic kidney disease (CKD),
      promoting renal secondary hyperparathyroidism and eventually resulting in
      hyperphosphatemia. Most agree that phosphate retention is a major contributor to
      the progression of CKD in many species and it is well known that
      hyperphosphatemia is associated with a significant mortality risk in humans with
      end-stage renal disease. PATIENT GROUP: Chronic kidney disease is a common
      ailment of geriatric cats. EVIDENCE BASE: There is evidence in cats suggesting
      that the use of a phosphate-restricted diet in IRIS stage 2-3 disease has a
      beneficial effect on clinical outcome. However, despite the fact that intestinal
      phosphate binders are commonly used in veterinary practice for patients with CKD,
      there have been few published reports focusing on the safety and efficacy of
      these products in veterinary medicine. No phosphorus binders are licensed as
      medications for dogs or cats. This article draws on data from clinical trials in
      humans and studies in cats to discuss treatment goals and options for phosphate
      retention and hyperphosphatemia in feline CKD. CLINICAL SIGNIFICANCE: With
      careful monitoring of serum phosphate and parathyroid hormone, and implementation
      of phosphate-restricted dietary management and intestinal phosphate binders,
      progression of CKD and the degree of hyperparathyroidism in cats may be reduced.
      AUDIENCE: Companion animal and feline practitioners are at the forefront in the
      management of CKD in cats.

PMID- 19857855
TI  - The Inappetent Hospitalised Cat: clinical approach to maximising nutritional
      support.
AB  - PRACTICAL RELEVANCE: Inappetence is one of the most common presenting complaints
      in clinically ill cats requiring hospitalisation. When prolonged, poor food
      intake can lead to malnutrition and may be associated with impaired metabolic
      function, immunosuppression, compromised wound healing, and increased morbidity
      and mortality. It is important to recognise that inappetence or anorexia is
      always secondary to another condition, and that treatment goals should be
      targeted at the primary condition. The current emphasis in the nutritional
      support of hospitalised inappetent cats is to provide more effective means of
      increasing nutritional intake--for example, by initiating enteral nutrition via
      feeding tubes-- rather than rely solely on traditional approaches such as
      increasing palatability of foods or using appetite-stimulating drugs. CLINICAL
      CHALLENGES: Cats that are ill enough to require hospitalisation are at increased
      risk of becoming malnourished because of the combined catabolic effects of their
      disease and poor nutritional intake. This article highlights some of the problems
      encountered in treating inappetent cats and discusses a clinical approach to
      providing better nutritional support. PATIENT GROUP: Inappetence and anorexia are
      associated with a myriad of clinical conditions in cats and can be seen in
      individuals of any age or breed. EQUIPMENT: Provision of nutritional support to
      cats may involve the use of feeding tubes such as naso-oesophageal or
      oesophagostomy tubes. In cases where enteral nutrition is not feasible (eg, cats
      with gastrointestinal failure), parenteral nutrition should be considered.
      EVIDENCE BASE: Various studies have documented the high prevalence of inappetence
      or anorexia in clinically ill cats. Additional studies have linked poor food
      intake in cats with serious sequelae such as immunosuppression and hepatic
      lipidosis. More recently, techniques for providing more effective nutritional
      support, such as oesophagostomy tubes, have been clinically evaluated and shown
      to be associated with minimal complications.

PMID- 19857856
TI  - Teen parenting. Foreword.

PMID- 19857857
TI  - Approaching the adolescent-headed family: a review of teen parenting.
AB  - In the USA, as many as 1 in 6 women nationwide become adolescent mothers, making
      adolescent pregnancy and childbearing issues a frequently encountered occurrence
      by pediatricians and adolescent medicine health care providers. Both social and
      medical programs focus on prevention and management of adolescent pregnancies;
      however, caring for the adolescent-headed family is less well understood. For
      many teen parents, various environmental and behavioral risks contributed to
      early childbearing and parenting. Following delivery of the infant, many of these
      same psycho-social, environmental, and educational factors continue to play a
      role in the teen's ability to parent effectively. This review explores these
      factors in relation to teen parenting as well as describes the limited data
      available on outcomes of adolescent mothers and their infants. Despite negative
      social stereotypes regarding adolescent fathers, research suggesting that most
      fathers desire involvement with their infants and the impact of and factors
      influencing father involvement is explored. Understanding the dynamics of the
      coparenting relationship, an expanding field of study, will aid practitioners in
      strengthening and supporting teen parenting by both mothers and fathers. As most
      teen parents continue to reside with their families, teen parenting has an
      important impact on the multi-generational family structure. These relationships
      can serve both to support and at times to hinder the adolescent parents'
      development as an individual and as a parent. Successful interventions and
      programs to support the adolescent-headed family take on various forms but are
      usually comprehensive and multidisciplinary and consider the developmental status
      of both the parent and the child. To best care for adolescent-headed families,
      pediatricians and adolescent medicine providers should understand the
      psychosocial, developmental, educational, and relationship issues that influence
      adolescent parenting.

PMID- 19857858
TI  - Prevalence and risk factors associated with musculoskeletal discomfort in New
      Zealand veterinarians.
AB  - A cross-sectional study using a modified Nordic musculoskeletal questionnaire
      asked 867 New Zealand veterinarians about the presence or absence of
      musculoskeletal discomfort (MSD). Participants were asked if MSD affected their
      normal activities and if it required any period(s) of absence from work.
      Additional questions enquired about work activities, psychosocial factors and
      workload. A binary logistic regression analysis was used to quantify the
      association between identified risk factors and the presence of MSD requiring
      absence from work in the previous 12 months, controlling for the presence of
      known confounders. The overall period prevalence of MSD was 96%, 67% had normal
      activities being affected and 18% of participants reported that they had been
      absent from work due to MSD. The lower back was the body site most commonly
      reported for MSD (73%). Factors increasing the odds of MSD requiring time off
      work for clinical veterinarians were 10 year increases in age (OR 1.26, 95% CI
      1.05-1.52), work involving awkward grip and hand movements 100% of time (OR
      12.91, 95% CI 3.46-4.21) and those who were dissatisfied with the level and
      difficulty of their work (OR 2.27, 95% CI 1.11-6.56). These findings have
      implications for health, lifestyle and retention rates for veterinarians.

PMID- 19857859
TI  - The effects of modifying interpretation bias on worry in generalized anxiety
      disorder.
AB  - This study investigated whether facilitating a benign interpretive bias decreases
      negative thought intrusions in generalized anxiety disorder (GAD). Clients were
      randomly allocated to an interpretation modification condition in which they
      repeatedly accessed benign meanings of emotionally ambiguous homographs and
      scenarios, or to a control condition in which they accessed threat and benign
      meanings with equal frequency. Worry frequency was assessed using a breathing
      focus task that involved categorising the valence of thought intrusions before
      and after an instructed worry period. Interpretation bias was assessed during the
      modification tasks, and on a different measure of interpretation bias (sentence
      completion) following a period of worry. The experimental procedure modified
      interpretations made during training, and in the later sentence completion task.
      Furthermore, compared to the control group, the benign group showed fewer
      negative thought intrusions during breathing focus (as rated by both participants
      and an assessor). These findings show that it is possible to induce a more benign
      interpretive bias in GAD clients and that this reduces negative thought
      intrusions.

PMID- 19857860
TI  - A test of the relations between avoidance of panic-related situations and
      substance use, substance dependence, and depression among subclinical panickers.
AB  - The hypotheses that among subclinical panickers, avoidance of panic-related
      situations would be associated with elevated substance use levels and increased
      likelihood of lifetime diagnoses of substance dependence and major depressive
      disorder (MDD) were tested. Findings confirmed that panic-related avoidance was
      associated with an elevated likelihood of lifetime diagnoses of nicotine and
      alcohol dependence as well as MDD, but not drug dependence. Panic avoidance was
      also related to relatively greater daily levels of cigarette and alcohol use.

PMID- 19857862
TI  - Designing an effective approach for obtaining methylenecarboxylate analogues of
      adenophostin A. Preliminary results.
AB  - Preliminary results for the synthesis of two new adenophostin analogues
      incorporating 3''- and 4''-methylenecarboxylate surrogate groups are presented.
      The synthesis involves the preparation of 3''- and 4''-methylenecarboxylate
      glucose derivatives by a radical allylation-oxidative cleavage approach, their
      conversion into thioglycoside precursors, and stereoselective glycosylation of a
      suitable adenosine derivative. The glycosylations proceeded with excellent
      stereoselectivity, only the alpha product was detected, and in good yields.

PMID- 19857861
TI  - Dielectric properties of two diastereoisomers of the arabinose and their
      equimolar mixture.
AB  - Dielectric relaxation measurements were performed on two enantiomers, D- and L
      arabinose and their equimolar mixture, and compared to dielectric data obtained
      for D-ribose. D-Arabinose differs from d-ribose by having the opposite
      configuration at C2. This study reveals that both D- and L- of arabinose exhibit
      alpha-relaxation peaks with the same shape for the same alpha-relaxation time
      tau(alpha), and the same steepness index for the T(g)-scale T-dependence of
      tau(alpha). However, the two isomers have slightly different glass transition
      temperatures T(g)'s, and their secondary gamma-relaxation times also differ
      slightly from the previously observed gamma-relaxation in D-ribose at the same
      temperature. However, when samples of both investigated monosaccharides are
      annealed at higher temperatures, their glass transition temperatures become
      nearly identical. This is an effect of the mutarotation process, which leads to
      the formation of pairs of the enantiomers and accordingly they should have the
      same physical properties. The width of the alpha-relaxation of D- and L-arabinose
      is broader than that of D-ribose, as reflected by the smaller stretch exponent in
      the Kohlrausch-Williams-Watts function used to fit the data of the former
      (beta(KWW)=0.46+/-0.01) than the latter (beta(KWW)=0.55+/-0.01). The width of the
      alpha-relaxation of racemic mixture of the D- and L-arabinose is slightly broader
      than that of the pure isomers. While the dielectric loss data of D-ribose in the
      glassy state at ambient and elevated pressures show an inflexion indicating the
      presence of the JG beta-relaxation, the data of D- and L-arabinose show no such
      feature for identification of the supposedly universal JG beta-relaxation.
      Nevertheless, on comparing the loss spectra of D-arabinose with that of D-ribose,
      the presence of the JG beta-relaxation in D-arabinose has been rationalized.

PMID- 19857863
TI  - Co-appearance of autoantibody-producing B220(low) B cells with NKT cells in the
      course of hepatic injury.
AB  - Severe hepatic injury is induced by Concanavalin A (Con A) administration in
      mice, the major effector cells being CD4(+) T cells, NKT cells and macrophages.
      Since autologous lymphocyte subsets are associated with tissue damage, Con A
      induced hepatic injury is considered to be autoimmune hepatitis. However, it has
      remained to be investigated how autoantibodies and B-1 cells are responsible for
      this phenomenon. In this study, it was demonstrated that autoantibodies which
      were detected using Hep-2 cells in immunofluorescence tests and using double
      strand (ds) DNA in the ELISA method, appeared after Con A administration (a peak
      at day 14). Moreover, autoantibody-producing B220(low) cells (i.e., B-1 cells)
      also appeared at this time. Purified B220(low) cells were found to have a
      potential to produce autoantibodies. These results suggest that Con A-induced
      hepatic injury indeed includes the mechanism of autoimmune hepatitis.

PMID- 19857864
TI  - Evidence for a link among cognition, language and emotion in cerebellar
      malformations.
AB  - We compared the neurobehavioral profiles of children with Joubert syndrome (JS
      participants), a rare autosomal recessive condition characterized on magnetic
      resonance imaging (MRI) by hypoplasia of the cerebellar vermis and midbrain
      hindbrain malformations, and children with malformations confined to the
      cerebellar vermis and one or both hemispheres (Cerebellar malformations--CM
      participants). We aimed at investigating the influence of anatomo-clinical
      similarities (vermian malformation) and differences (intact cerebellar
      hemispheres vs sparing of the pons, respectively) with respect to cognitive,
      linguistic and emotional development, assuming as a reference framework the
      Cerebellar Cognitive Affective Syndrome (CCAS). Results show that severe to
      moderate mental retardation is infrequent in JS children, while it is present in
      more than half the sample of CM children. Affect development was generally
      preserved in JS, in high-functioning CM individuals and also in some of the CM
      children with moderate mental retardation, which raised questions as to the role
      of a cerebellar vermis lesion in determining affect disorders. Further, cognitive
      and linguistic profiles on both intellectual and neuropsychological evaluations
      provided evidence for distinct patterns of peaks and valleys in the two groups,
      with JS children being significantly more impaired in language and verbal working
      memory and CM individuals showing a significant impairment of executive functions
      and emotional development. The overall evidence provides support for an important
      role of cerebellar structures per se in shaping emotional, cognitive and
      linguistic development, when vermian lesions are associated to cerebellar
      hemispheric lesions. Cerebellar vermis and brainstem lesions instead appear to
      have a major impact on motor-related skills, including oro-motor abilities and
      verbal working memory.

PMID- 19857865
TI  - Modified Smith predictor for frequency identification and disturbance rejection
      of single sinusoidal signal.
AB  - This paper presents a frequency identification and disturbance rejection scheme
      for open loop stable time delay systems with disturbance containing a constant
      signal and a single sinusoidal signal. Astrom's modified Smith predictor is
      employed to maintain good setpoint tracking performance. Disturbance rejection
      controller is designed via internal model control principle and functions as a
      finite dimensional repetitive controller. Extended Kalman filter is designed to
      track the frequency of unknown periodic disturbance. The simulation results
      demonstrate the successful performance of the proposed disturbance rejection
      method for controlling a linear system with time delays, subjected to both step
      and sinusoidal disturbances.

PMID- 19857866
TI  - Passive nonlinear elastic behaviour of skeletal muscle: experimental results and
      model formulation.
AB  - The goal of this study was to characterize the passive elastic behaviour of
      muscle and tendon tissues of rat tibialis anterior. For that purpose, tissue
      samples from 3 month old female Wistar rats (210+/-11g) were mechanically tested
      in vitro. Moreover, an in vivo device was developed to measure the muscle-tendon
      unit response to increasing load. Mechanical tests, consisting of uniaxial
      loading along the longitudinal axis of tendon and muscle strips, revealed the
      nonlinear mechanical behaviour of these tissues. A material model was formulated
      and its parameters fit to the experimental data using the Levenberg-Marquardt
      optimization algorithm. The fit goodness was assessed and R(2) values close to 1
      and very low epsilon values were obtained. The passive behaviour of a future
      finite element model of a muscle-tendon unit will be validated against the in
      vivo passive extension tests by comparing the reaction force-extension curves.

PMID- 19857867
TI  - Evaluation of silica gel-immobilized phosphorylcholine columns for size exclusion
      chromatography and their application in the analysis of the subunit structures of
      fish-egg lectins.
AB  - Columns of phosphorylcholine (PC) immobilized on silica gel were shown to be
      useful for size exclusion chromatography (SEC) of proteins. The columns provided
      good separation of proteins in 50mM sodium phosphate buffer (pH 6.9) containing
      0.25 M NaCl, and there was a linear relationship between the retention times and
      the logarithmic values of the molecular weights with a correlation coefficient
      (R(2)) of 0.978-0.992. The columns were used in analyzing the subunit structures
      of the rhamnose-binding lectins CSL1, CSL2, and CSL3, isolated from chum salmon
      (Oncorhynchus keta) eggs. Although the lectins, which are a group of carbohydrate
      binding and hydrophobic proteins, behaved anomalously in SEC with conventional
      matrices, they could be eluted from the immobilized PC columns without non-size
      related retention, thereby allowing their molecular weights to be reliably
      estimated.

PMID- 19857868
TI  - Method for determination of fatty acid amides in polyethylene packaging materials
      -gas chromatography/mass spectrometry.
AB  - A new method for determination of fatty acid amides in polyethylene packaging
      film was developed using gas chromatography/mass spectrometry (GC/MS). Liquid
      extraction, Soxhlet extraction ultrasonic-assisted extraction and pressurized
      solvent extraction (PSE) methods were compared and the results showed that
      pressurized solvent extraction was the best for extracting these compounds. After
      extraction, solvent was blown by nitrogen and a trifluoroethyl derivation step
      was carried out. The derivative compounds were identified and quantified by GC/MS
      using an HP-Innowax column. The retention times were 6.20 min for derivative
      hexadecanoamide, 8.56 min for derivative octadecanamide, 8.84 min for derivative
      oleamide and 13.68 min for derivative erucamide, respectively. The detection
      limits were 61.0 ng g(-1), 74.0 ng g(-1), 103.0 ng g(-1), and 105.0 ng g(-1),
      respectively, and the linearity were good. The proposed method was applied
      satisfactorily to determine these chemicals in different types of polyethylene
      samples.

PMID- 19857869
TI  - Quantum chemical characterization of Abraham solvation parameters for gas-liquid
      chromatographic stationary phases.
AB  - Quantum chemical based investigation is presented on the Abraham solvation
      parameters for 23 molecular (non-polymeric) GLC stationary phases. PM6
      semiempirical calculations combined with conductor-like screening model (COSMO)
      have been utilized. Comprehensive search for an optimal model was carried out,
      based on best subset selection from 86 variables considered. A unified
      quantitative structure-property relationship model has been developed for all
      five Abraham parameters reported. The selected set of five structure-driven
      descriptors was subjected to statistical analyses, and was shown to be useful for
      stationary phase classification.

PMID- 19857870
TI  - Pre-concentration of phenolic compounds in water samples by novel liquid-liquid
      microextraction and determination by gas chromatography-mass spectrometry.
AB  - Pre-concentration and determination of 8 phenolic compounds in water samples has
      been achieved by in situ derivatization and using a new liquid-liquid
      microextraction coupled GC-MS system. Microextraction efficiency factors have
      been investigated and optimized: 9 microL 1-undecanol microdrop exposed for 15
      min floated on surface of a 10 mL water sample at 55 degrees C, stirred at 1200
      rpm, low pH level and saturated salt conditions. Chromatographic problems
      associated with free phenols have been overcome by simultaneous in situ
      derivatization utilizing 40 microL of acetic anhydride and 0.5% (w/v) K(2)CO(3).
      Under the selected conditions, pre-concentration factor of 235-1174, limit of
      detection of 0.005-0.68 microg/L (S/N=3) and linearity range of 0.02-300 microg/L
      have been obtained. A reasonable repeatability (RSD< or =10.4%, n=5) with
      satisfactory linearity (0.9995> or =r(2)> or =0.9975) of results illustrated a
      good performance of the present method. The relative recovery of different
      natural water samples was higher than 84%.

PMID- 19857871
TI  - A fast derivatization procedure for gas chromatographic analysis of
      perfluorinated organic acids.
AB  - A rapid and simple derivatization procedure has been developed for gas
      chromatographic determination of perfluorinated organic acids (PFCAs, C(6)
      C(12)), using isobutyl chloroformate (IBCF) to convert the acids into the more
      volatile isobutyl esters, under catalysis by pyridine. The procedure was
      optimized in an acetonitrile medium and applied to GC techniques with electron
      capture detection (GC-ECD) and mass spectrometry with electron-impact ionization
      (GC-EI-MS); for the sake of comparison, HPLC with electrospray-ionization MS
      (HPLC-ESI(-)-MS) was also tested. The LOD and LOQ values obtained for these three
      techniques were compared, and the lowest LODs were obtained with GC-ECD (0.06
      1.80 microg mL(-1)). The procedure was further optimized in an aqueous medium,
      obtaining the best results in a phosphate buffer (pH 2.5, 50 mmol L(-1)), in
      which the LOD and LOQ values were measured for GC-ECD a GC-EI-MS. The lowest LODs
      were found for GC-EI-MS (0.030-0.314 microg mL(-1)). The practical applicability
      was tested on Vltava river water samples.

PMID- 19857872
TI  - Surface immobilization of fibronectin-derived PHSRN peptide on functionalized
      polymer films--effects on fibroblast spreading.
AB  - The Pro-His-Ser-Arg-Asn (PHSRN) sequence in fibronectin is a second cell-binding
      site that synergistically affects Arg-Gly-Asp (RGD). The PHSRN peptide also
      induces cell invasion and accelerates wound healing. We report on the surface
      immobilization of PHSRN by spontaneous adsorption on polysiloxane thin films
      which have different surface free energy characteristics. Low-surface energy
      (hydrophobic) polysiloxane and the corresponding high-surface energy
      (hydrophilic) surfaces obtained by UV-ozone treatments were used as adsorbing
      substrates. The peptide adsorption process was investigated by quartz crystal
      microbalance with dissipation monitoring and atomic force microscopy. Both
      adsorption kinetics and peptide rearrangement dynamics at the solid interface
      were significantly different on the surface-modified films compared to the
      untreated ones. Fibroblast cells cultures at short times and in a simplified
      environment, i.e., a medium-free solution, were prepared to distinguish
      interaction events at the interface between cell membrane and surface-immobilized
      peptide for the two cases. It turned out that the cell-adhesive effect of
      immobilized PHSRN was different for hydrophobic compared to hydrophilic ones.
      Early signatures of cell spreading were only observed on the hydrophilic
      substrates. These effects are explained in terms of different spatial
      arrangements of PHSRN molecules immobilized on the two types of surfaces.

PMID- 19857873
TI  - Phosphate uptake behavior of ZnAlZr ternary layered double hydroxides through
      surface precipitation.
AB  - Tetravalent Zr(4+) ion incorporated ZnAl hydrotalcite-like material with varying
      Zn/(Al+Zr) atomic ratio (2-4) and Al/Zr atomic ratio 0.7:0.3 with CO(3)(2-) as
      interlayer anion were successfully synthesized and characterized by various
      physicochemical methods. The phosphate uptake studies were carried out over these
      materials by batch method with the objective of enhancing the uptake through
      creation of higher positive charge on brucite-like layers by the incorporation of
      Zr(4+). The studies revealed that ternary ZnAlZr hydrotalcites show good uptake
      capacity for phosphate, among which ZnAlZr4-HT depicts a maximum uptake of around
      91 mg P/g. We observed that phosphate uptake results in the formation of layered
      hopeite mineral (Zn(3)(PO(4))(3) x 4 H(2)O) on the surface of material by the
      surface precipitation of dissolved zinc ion through the outer-sphere complex
      formation of phosphate. The phosphate uptake increases with a decrease in Zn/Al
      and Zn/(Al+Zr) atomic ratios. Effects of initial phosphate concentration, contact
      time, adsorbent amount and temperature variation on phosphate uptake were
      studied. Co-presence of competitive anion like nitrate enhances the uptake of
      phosphate to 148 mg P/g. Recycle studies of the material shows a decrease in the
      uptake of phosphate with the number of cycles due to an increase in the
      crystallinity. Very high uptake of phosphate by these materials even in the
      presence of other anions/cations suggests their potential role in waste water
      remediation.

PMID- 19857874
TI  - Aggregation states of rhodamine 6G in electrospun nanofibrous films.
AB  - Novel fluorescent composite nanofibrous films of rhodamine 6G (Rh6G) and
      polyacrylonitrile (PAN) are first prepared by electrospinning. The aggregation
      states of Rh6G in electruspun nanofibrous films are studied as a function of
      concentrations and characterized by UV-vis absorption spectroscopy and emission
      and excitation fluorescence spectroscopy. We have also used casting films as
      reference material to compare the effect of incorporation of Rh6G in electrospun
      nanofibrous films and casting films. The large specific surface area of the
      nanofibers and fast evaporation of the solvents in the electrospinning process
      reduced the aggregation of Rh6G. The appearance of fluorescent J-type dimers,
      even at higher dye concentration in elctrospun films, demonstrates that the
      electrospun films are an ideal material for incorporation of fluorescent dyes.

PMID- 19857875
TI  - Dry etching of colloidal crystal films.
AB  - Two types of non-close-packed colloidal crystal films were prepared by etching
      the films made of polystyrene nanospheres using a hyperthermal neutral beam of
      oxygen gas. Etching without sintering above glass transition temperature of the
      polymer particles resulted in the non-close-packed structure of the nanospheres,
      in which polystyrene nanospheres in different lattice planes touched each other
      due to the reduction in the size of the nanospheres that occurred during the
      etching process. In contrast, a different non-close-packed structure with inter
      connecting networks between etched nanospheres was generated by annealing of the
      colloidal crystal and a subsequent etching process. The photonic bandgap could be
      tuned during this dry etching of colloidal photonic crystals. This connected open
      structure could be used as a template for a silica inverse opal by chemical vapor
      deposition. An alternative dry etching process, reactive ion etching, mainly
      affected the morphology of particles near the top surface, and only a slight
      change in the stop band position of the colloidal crystal film was observed.

PMID- 19857876
TI  - Theory of mind enhances preference for fairness.
AB  - The purpose of the current study was to examine the role of theory of mind in
      fairness-related behavior in preschoolers and to introduce a tool for examining
      fairness-related behavior in children. A total of 68 preschoolers played the
      Ultimatum Game in a face-to-face setting. Acquisition of theory of mind was
      defined as the understanding of false beliefs using the Sally-Anne task. The
      results showed that preschoolers who had acquired theory of mind proposed higher
      mean offers than children who had not acquired theory of mind. These findings
      imply that the ability to infer the mental states of others plays an important
      role in fairness-related behavior.

PMID- 19857877
TI  - Phytoplankton viability in ballast water from international commercial ships
      berthed at ports in Korea.
AB  - We investigated the viability of phytoplankton from ballast water of
      international commercial ships berthed at the ports of Ulsan and Onsan, Korea.
      The incubation conditions used were temperatures of 13 degrees C to represent
      ambient water and 20 degrees C to represent the thermal optimum, as well as
      nutrients in ballast water, shipside water, and F/2 medium. Phytoplankton in new
      (approximately 7 days) and old (20 and 2 days) ballast water survived when
      incubated under the nutrients typical of shipside water and F/2 medium at 13
      degrees C and 20 degrees C. Colonization process was mostly dominated by
      Skeletonema costatum, Cylindrotheca closterium and pennate diatoms (<10 microm in
      diameter). S. costatum and C. closterium were persistent during incubation time,
      whereas pennate diatoms dominated in the three types of media from doubling to
      last phase of growth. This study showed that bloom-forming and pennate diatoms
      appear to be the species most likely to become successfully established in the
      two ports.

PMID- 19857878
TI  - Comparison of the effects of pollution on the marine bivalve Donax trunculus in
      the vicinity of polluted sites with specimens from a clean reference site
      (Mediterranean Sea).
AB  - The physiological and biochemical characteristics of tissue samples of the marine
      mussel, Donax trunculus, from an oil-polluted site (Qiryat Yam) and from a site
      adjacent to an industrial factory (Frutarom) producing polyvinyl chloride (PVC)
      were compared with samples from a clean reference site (Akko). All sites were
      located along the sandy shores of the Israeli Mediterranean Sea. The mussels from
      the oil-polluted site showed increased activity of the system of active transport
      of organic anions (SATOA) in the gills and the renocardial organ and also of the
      multixenobiotic resistance transporter (MXR) in the gills. In contrast, samples
      collected near the PVC factory showed a decrease in SATOA activity and no
      increase in the activity of MXR in the gills. Specimens from the reference site
      demonstrated a redox state of equilibrium between energy production and
      utilization, while in Donax from both the oil polluted and the PVC-polluted
      sites, the mitochondrial redox state reflected intensive consumption of energy.
      No significant changes were found in the activity of reduced glutathione s
      transferase (GST) in the cytosolic fraction of the digestive gland of Donax
      collected from any of the three sites. The data demonstrate a differential
      increase in the anti-chemical defense systems and an intensification of energy
      metabolism in the mussels exposed to pollution.

PMID- 19857879
TI  - Biodiversity loss in benthic macroinfaunal communities and its consequence for
      organic mercury trophic availability to benthivorous predators in the lower
      Hudson River estuary, USA.
AB  - Organic mercury such as methylmercury is not only one of the most toxic
      substances found in coastal ecosystems but also has high trophic transfer
      efficiency. In this study, we examined implications of chronically altered
      benthic macroinfaunal assemblages for organic mercury trophic availability (based
      on organic mercury intracellular partitioning) to their predators in the Arthur
      Kill-AK (New York, USA). Despite low species diversity, both density and biomass
      of benthic macroinvertebrates in AK were significantly higher than those at the
      reference site. Disproportionately high biomass of benthic macroinvertebrates
      (mostly polychaetes) in the northern AK resulted in a more than twofold increase
      ('ecological enrichment') in the trophically available organic mercury pool.
      These results suggest that altered benthic macroinfaunal community structure in
      AK may play an important role in organic mercury trophic availability at the base
      of benthic food webs and potentially in mercury biogeochemical cycling in this
      severely urbanized coastal ecosystem.

PMID- 19857880
TI  - Risk formulation for the sonic effects of offshore wind farms on fish in the EU
      region.
AB  - In 2007, European leaders agreed to source 20% of their energy needs from
      renewable energy; since that time, offshore wind farms have been receiving
      attention in the European Union (EU). In 2008, the European Community submitted a
      proposal to the United Nations Environment Program (UNEP) in order to combat
      marine noise pollution. In consideration of these facts, the present paper aims
      to deduce a preliminary hypothesis and its formulation for the effect of offshore
      wind farm noise on fish. The following general picture is drawn: the short-term
      potential impact during pre-construction; the short-term intensive impact during
      construction; and the physiological and/or masking effects that may occur over a
      long period while the wind farm is in operation. The EU's proposal to UNEP
      includes noise databases that list the origins of man-made sounds; it is
      advisable that offshore wind farms should be listed in the noise databases in
      order to promote rational environment management.

PMID- 19857881
TI  - Antibacterial clerodane diterpenes from Goldenrod (Solidago virgaurea).
AB  - Nine clerodane diterpenes, solidagoic acids C-I (1-7), cleroda-3,13(14)-dien
      16,15:18,19-diolide (8) and cleroda-3,13(14)-dien-15,16:18,19-diolide (9) were
      isolated and characterised from the ethanol-ethyl acetate (1:1) extract of
      Solidago virgaurea. The structures were determined by NMR spectroscopic analysis.
      Several displayed moderate antibacterial activity against Staphylococcus aureus.

PMID- 19857882
TI  - Regulation of ginsenoside and phytosterol biosynthesis by RNA interferences of
      squalene epoxidase gene in Panax ginseng.
AB  - Squalene epoxidase catalyzes the first oxygenation step in phytosterol and
      triterpenoid saponin biosynthesis and is suggested to represent one of the rate
      limiting enzymes in this pathway. Here, we investigated the roles of two squalene
      epoxidase genes (PgSQE1 and PgSQE2) in triterpene and phytosterol biosynthesis in
      Panax ginseng. PgSQE1 and PgSQE2 encoded deduced proteins of 537 and 545 amino
      acids, respectively. Amino acid sequences deduced from PgSQE1 and PgSQE2 share
      83% homology, but the N-terminal regions (first 60 amino acids) are highly
      different. PgSQE1 mRNA abundantly accumulated in all organs. PgSQE2 was only
      weakly expressed and preferentially in petioles and flower buds. Methyl jasmonate
      (MeJA) treatment enhanced the accumulation of PgSQE1 mRNA in roots, but rather
      suppressed expression of PgSQE2. Precursor (squalene) treatment coordinately
      upregulated the expression of both PgSQE1 and PgSQE2. In situ hybridization
      analysis established that both PgSQE1 and PgSQE2 mRNAs accumulated preferentially
      in vascular bundle tissue and resin ducts of petioles. RNA interference of PgSQE1
      in transgenic P. ginseng completely suppressed PgSQE1 transcription.
      Concomitantly, the interference of PgSQE1 resulted in reduction of ginsenoside
      production. Interestingly, silencing of PgSQE1 in RNAi roots strongly upregulated
      PgSQE2 and PNX (cycloartenol synthase) and resulted in enhanced phytosterol
      accumulation. These results indicate that expression of PgSQE1 and PgSQE2 were
      regulated in a different manner, and that PgSQE1 will regulate ginsenoside
      biosynthesis, but not that of phytosterols in P. ginseng.

PMID- 19857883
TI  - Family history of acute myocardial infarction and/or arterial hypertension and
      the adoption of 'heart healthy' habits: The Cantabria subcohort of the SUN
      project.

PMID- 19857884
TI  - Modeling of flexible waveguides for ultrasonic vibrations transmission:
      longitudinal and flexural vibrations of non-deformed waveguide.
AB  - The article presents the mathematical model allowing to investigate longitudinal
      and flexural vibrations of stepped flexible waveguides with transitional section
      without regard to various vibration modes interaction. The model uses original
      numerical-analytic calculations based on analytical solutions of the equation of
      waveguide steps vibrations and their continuous matching with numerical solution
      of the equation of transitional section vibrations. The proposed model can be
      considered as an initial approximation to the solution of the problem of flexible
      waveguides design, which makes it possible to determine and validate effective
      methods of its addressing. Resonant curves of longitudinal and flexural
      vibrations of two-step waveguide are traced for the given vibration frequency.
      Step lengths values providing simultaneous resonance of longitudinal and flexural
      vibrations for the given frequency are determined. Validity of the proposed model
      is proved by the results of finite elements method (FEM) modeling using ANSYS
      software. Application of Timoshenko's model instead of Euler-Bernoulli's model
      for description of flexural vibrations enabled reduction of relative deviation of
      resonant frequencies calculated using ANSYS from the value specified during
      resonant curves tracing down to negligible value (0.17%).

PMID- 19857885
TI  - Ultrasound-assisted microbubbles gene transfer in tendons for gene therapy.
AB  - Our study aimed at evaluating the use of ultrasound-assisted microbubbles gene
      transfer in mice Achilles tendons. Using a plasmid encoding luciferase gene, it
      was found that an efficient and stable gene expression for more than two weeks
      was obtained when tendons were injected with 10 microg of plasmid in the presence
      of 5x10(5) BR14 microbubbles with the following acoustic parameters: 1 MHz, 200
      kPa, 40% duty cycle and 10 min of exposure time. The rate of gene expression was
      100-fold higher than that obtained with naked plasmid injected alone without
      ultrasound or with ultrasound in absence of microbubbles. The long term
      expression of transgene makes ultrasound-assisted microbubble a suitable method
      for gene therapy in tendons.

PMID- 19857886
TI  - Circumferential thermoelastic waves in orthotropic cylindrical curved plates
      without energy dissipation.
AB  - In this article, the propagation of guided thermoelastic waves in the
      circumferential direction of orthotropic cylindrical curved plates subjected to
      stress-free, isothermal boundary conditions is investigated in the context of the
      Green-Naghdi (GN) generalized thermoelastic theory (without energy dissipation).
      The coupled wave equations and heat conduction equation are solved by the
      Legendre orthogonal polynomial series expansion approach. The convergency of the
      method is discussed through a numerical example. The dispersion curves of thermal
      modes and elastic modes are illustrated simultaneously. Dispersion curves of the
      corresponding pure elastic cylindrical plate are also shown to analyze the
      influence of the thermoelasticity on elastic modes. The displacement, temperature
      and stress distributions are shown to discuss the differences between the elastic
      modes and thermal modes. A thermoelastic cylindrical plate with a different ratio
      of radius to thickness is considered to discuss the influence of the ratio on the
      characteristics of circumferential thermoelastic waves.

PMID- 19857887
TI  - Wave guide imaging through Time Domain Topological Energy.
AB  - Time Domain Topological Energy (TDTE), uses the reflected ultrasonic field
      recorded by an array of transducers placed on the boundary of the inspected
      medium. Two numerical determinations (forward and adjoint problems) of the
      acoustical field inside a reference medium are necessary to compute an image.
      Topological Energy is defined as a variation of topological sensitivity or
      gradient and comes from the field of mathematical optimisation. Recent
      developments for Non-Destructive Testing have shown the analogy with Time
      Reversal concepts. Time Reversal mirrors have been employed for various
      applications in a wide number of situations including wave guides where very good
      re-focalization performances have been obtained with a reduced number of
      transducers instead of an array of transducers. Moreover recent works have
      enlightened that the reverberation properties of a wave guide allow to re
      focalize using Time Reversal with only one transducer. For TDTE imaging a single
      transducer placed at one end of a wave guide has been modelled. The boundaries of
      the wave guide create virtual sources that can be understood as a virtual array
      of transducers. Numerical and experimental results are presented using TDTE and a
      single transducer in a wave guide for targets and conditions of increasing
      complexity.

PMID- 19857888
TI  - Design features of a three-dimensional molar crown and related maximum principal
      stress. A finite element model study.
AB  - OBJECTIVE: To evaluate the effects of clinically relevant variables on the
      maximum principal stress (MPS) in the veneer layer of an anatomically correct
      veneer-core-cement-tooth model. METHODS: The average dimensions of a mandibular
      first molar crown were imported into CAD software; a tooth preparation was
      modeled by reducing the proximal walls by 1.5 mm and the occlusal surface by 2.0
      mm. 'Crown systems' were composed by varying characteristics of a cement layer,
      structural core, and veneer solid, all designed to fit the tooth preparation. The
      main and interacting effects of proximal wall height reduction, core material,
      core thickness, cement modulus, cement thickness, and load position on the
      maximum stress distribution were derived from a series of finite element models
      and analyzed in a factorial analysis of variance. RESULTS: The average MPS in the
      veneer layer over the 64 models was 488 MPa (range = 248-840 MPa). MPS increased
      significantly with the addition of horizontal load components and with increasing
      cement thickness. In addition, MPS levels varied as a function of interactions
      between: proximal wall height reduction and load position; load position and
      cement thickness; core thickness and cement thickness; cement thickness and
      proximal wall height reduction; and core thickness, cement thickness and proximal
      wall height reduction. CONCLUSION: Rational design of veneered structural
      ceramics must consider the complex geometry of the crown-tooth system and
      integrate the influence of both the main effects and interactions among design
      parameters.

PMID- 19857890
TI  - Toxicological characteristics of nanoparticulate anatase titanium dioxide in
      mice.
AB  - In an effort to examine liver injury, immune response, and other physiological
      effects in mice caused by intragastric administration of nanoparticulate anatase
      titanium dioxide (5nm), we assessed T lymphocytes, B lymphocyte and NK lymphocyte
      counts, hematological indices, biochemical parameters of liver functions, and
      histopathological changes in nanoparticulate titanium dioxide -treated mice.
      Indeed, mice treated with higher dose nanoparticulate titanium dioxide displayed
      a reduction in body weight, an increase in coefficients of the liver and
      histopathological changes in the liver. Specifically, in these nanoparticulate
      titanium dioxide -treated mice, interleukin-2 activity, white blood cells, red
      blood cells, haemoglobin, mean corpuscular haemoglobin concentration,
      thrombocytes, reticulocytes, T lymphocytes (CD3(+), CD4(+), CD8(+)), NK
      lymphocytes, B lymphocytes, and the ratio of CD4 to CD8 of mice were decreased,
      whereas NO level, mean corpuscular volume, mean corpuscular haemoglobin, red
      (cell) distribution width, platelets, hematocrit, mean platelet volume of mice
      were increased. Furthermore, liver functions were also disrupted, as evidenced by
      the enhanced activities of alanine aminotransferase, alkaline phosphatase,
      aspartate aminotransferase, lactate dehydrogenase and cholinesterase, an increase
      of the total protein, and the reduction of ratio of albumin to globulin, the
      total bilirubin, triglycerides, and the total cholesterol levels. These results
      suggested that the liver function damage observed in mice treated with higher
      dose nanoparticulate titanium dioxide is likely associated with the damage of
      haemostasis blood system and immune response. However, low dose nanoparticulate
      anatase TiO(2) has little influences on haemostasis blood system and immune
      response in mice.

PMID- 19857889
TI  - Osteogenic differentiation of human amniotic fluid-derived stem cells induced by
      bone morphogenetic protein-7 and enhanced by nanofibrous scaffolds.
AB  - Amniotic fluid-derived stem cells (AFSCs) are becoming an important source of
      cells for regenerative medicine given their apparent advantages of accessibility,
      renewal capacity and multipotentiality. In the intermediate stage between the
      embryonic stem cells (ESCs) and adult stem cells, AFSCs may have a distinct
      mechanism to choose their fate. Unfortunately, until now, little is known about
      how bone morphogenetic proteins (BMPs) control the osteoblastic differentiation
      of AFSCs, especially on 3D scaffolds. Our research shows that human AFSCs
      (hAFSCs) can be induced for osteoblastic differentiation by rhBMP-7, and hAFSCs
      respond to rhBMP-7 more strongly than human mesenchymal stem cells (hMSCs). As
      synthetic ECM, scaffolds play a central role in tissue engineering. The hAFSCs,
      on the nanofibrous scaffolds (NF scaffolds) with morphology similar to that of
      natural collagen fibers, showed significantly enhanced alkaline phosphatase (ALP)
      activity, calcium content, von Kossa staining and the expression of osteogenic
      genes than those on the traditional scaffolds, i.e. solid walled scaffolds. The
      data on the bone formation in vivo presented further evidence that biomimetic NF
      scaffolds provided hAFSCs a more favorable synthetic ECM, and thus, facilitated
      the osteogenic differentiation of hAFSCs. The relative strong responsiveness to
      rhBMP-7 makes hAFSCs promising in bone regeneration. The synthetic NF scaffolds,
      which mimic the morphology of natural collagen fibers, enhanced the osteoblastic
      differentiation of hAFSCs in vitro and bone formation in vivo.

PMID- 19857891
TI  - Nanoscale protein-based memory device composed of recombinant azurin.
AB  - In this present study, a nanoscale protein-based memory device consisting of
      recombinant azurin with its cysteine residues modified by site-directed
      mutagenesis method has been developed. Cysteine residues were modified to
      directly coordinate with the gold surface without use of any chemical linkers.
      Cyclic voltammetry (CV) method was used to measure the redox behavior of the
      immobilized azurin. Open-circuit potential amperometry (OCPA) technique allowed
      observing the memory characteristics including "write", "erase" and "read"
      functions of a nanoscale memory device. The variations in topology and the
      electron transfer properties, under the application of redox potentials, of the
      azurin adsorbed on Au was accomplished with electrochemical scanning tunneling
      microscopy. Data storage is achieved by applying redox potentials which are
      within the range of 500 mV. Finally the reliability of the proposed device has
      been examined. The key performance of the present system is it enables the memory
      working mechanism at nanoscale without degradation in performance and hence can
      be used as a nanoscale information storage device.

PMID- 19857892
TI  - Molecular design of chitosan gene delivery systems with an optimized balance
      between polyplex stability and polyplex unpacking.
AB  - Chitosan is an attractive gene delivery vehicle, but the criteria and strategies
      for the design of efficient chitosan gene delivery systems remain unclear. The
      purpose of this work was to investigate how the strength of the charge-based
      interaction between chitosan and DNA determines the gene expression levels and to
      design chitosan vectors with an optimized balance between polyplex stability and
      polyplex unpacking. Using 21 formulations based on low molecular weight chitosans
      with constant charge density and a number-average degree of polymerization (DPn)
      in the range of 21-88 (M(w) 4.7-33kDa), we studied the relationship between the
      chain length and the formulation properties, cellular uptake of polyplexes and
      gene transfer efficacy. We were able to identify a narrow interval of DPn31-42
      that mediated the maximum level of transgene expression. An increase in chain
      length and/or the amino-phosphate (A/P) ratio reduced and delayed transgene
      expression. Compared to DPn31, transfection with the same amount of DPn72 or
      DPn88 resulted in 10-fold-lower expression levels. The gene transfer pattern
      correlated with the ability of heparin to release DNA from the polyplexes. As a
      tool to facilitate the unpacking of the polyplexes, we substituted the chitosans
      with uncharged oligosaccharides that reduced the interaction with DNA. The
      substitution of chitosans that originally yielded too stable polyplexes, such as
      DPn72 and DPn88 resulted in a 5-10-fold enhancement of the expression levels.
      However, the substitution of chitosans shorter than DP28 completely abolished
      transfection. Tailoring of the chain length and the substitution of chitosan were
      shown to be feasible tools to modulate the electrostatic interactions between the
      chitosan and DNA and to design chitosans with an optimized balance between
      polyplex stability and polyplex unpacking.

PMID- 19857893
TI  - The influence of rat mesenchymal stem cell CD44 surface markers on cell growth,
      fibronectin expression, and cardiomyogenic differentiation on silk fibroin -
      Hyaluronic acid cardiac patches.
AB  - Since MSCs contain an abundant of CD44 surface markers, it is of interesting to
      investigate whether CD44 on rat MSC (rMSCs) influenced cell growth, fibronectin
      expression and cardiomyogenic differentiation on new SF/HA cardiac patches. For
      this investigation, we examined the influences of rMSCs with or without a CD44
      blockage treatment on the aforementioned issues after they were cultivated, and
      further induced by 5-aza on SF and SF/HA patches. The results showed that the
      relative growth rates of rMSCs cultured on cultural wells, SF/HA patches without
      or with a CD44-blockage treatment were 100%, 208.9+/-7.1 (%) or 48.4+/-6.0 (%)
      (n=3, for all), respectively, after five days of cultivations. Moreover, rMSCs
      cultivated on SF/HA patches highly promoted fibronectin expressions (e.g.,
      1.8x10(5)/cell, in fluorescent intensity) while cells with a CD44-blockage
      treatment markedly diminished the expressions (e.g., 1.1x10(4)/cell, in
      fluorescent intensity) on same patches. For investigating possible influences of
      CD44 surface markers of rMSCs on their cardiomyogenic differentiation, the
      expressions of specific cardiac genes of cells were examined by using real-time
      PCR analysis. The results indicated that 5-aza inducing rMSCs significantly
      promoted the expressions of Gata4, Nkx2.5, Tnnt2 and Actc1 genes (all, P<0.01 or
      better, n=3) on SF/HA patches compared with those expressions on SF patches and
      for cells with a CD44-blockage treatment on SF/HA patches. Furthermore, the
      intensity of the expressions of cardiotin and connexin 43 of 5-aza inducing rMSCs
      were markedly higher than those of cells with a CD44-blockage treatment after
      they were cultured on SF/HA patches. Through this study, we reported that CD44
      surface markers of rMSCs highly influenced the proliferations, fibronectin
      expressions and cardiomyogenic differentiation of rMSCs cultivated on cardiac
      SF/HA patches.

PMID- 19857894
TI  - Neuronal cell growth on iridium oxide.
AB  - Iridium oxide is an attractive material for the development of novel multi
      electrode array (MEA) systems that provide electrodes for stimulation as well as
      recording single neurons. In this study the biocompatibility of pure iridium and
      different iridium oxides that differ characteristically in their surface
      roughness was investigated using two different biological test systems, insect
      and vertebrate neurons. Iridium oxide surfaces were coated with Concanavalin A
      and poly-(D)-lysine. In detailed investigations (R(a) value determination,
      contact angle measurement, marker enzyme assay) the surface characteristics of
      non-modified and coated iridium oxide films were analysed, demonstrating that the
      materials can be successfully coated. Furthermore, we show that locust neurons
      grow well on all substrates tested, while chicken neurons need coated surfaces
      for proper adhesion. Increasing the roughness of iridium oxide films, which in
      principle could improve cell adhesion, did not improve the neurocompatibility.
      These results show that in future applications iridium oxide films can be used
      with surface morphologies previously shown to be optimal for stimulation purposes
      (cauliflower-like surface structure).

PMID- 19857895
TI  - Pharmacological activity and protein phosphorylation caused by nitric oxide
      releasing microparticles.
AB  - Nitric oxide (NO)-releasing microparticles were developed as a potential
      treatment option against various blood flow irregulations including sexual
      dysfunction, atherosclerosis and metal stent-induced restenosis. Polymeric
      microparticles containing diethylenetriamine diazeniumdiolate (DETA NONOate), a
      NO donor, were prepared using modified double-emulsion solvent evaporation method
      to maximize the loading efficacy and stability of DETA NONOate. The
      pharmacological effects of the NO-releasing microparticles were evaluated by
      examining the changes in the vaginal blood flow in rats. The effects of NO on the
      phosphorylation of protein kinase C (PKC) and mitogen activated protein (MAP)
      kinases in excised vaginal mucosa, such as extracellular signal-regulated kinase
      1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38, were examined using
      immunoblotting technique to determine whether NO activates PKC, which
      subsequently plays an integral role in the formation of PKC-MAP kinase modules.
      The viability of vagina cells (VK2E6E7) upon exposure to NO-releasing
      microparticles was examined for cytotoxicity assessment. In contrast to rapid and
      short-term effects of non-formulated DETA NONOate, microparticles containing DETA
      NONOate exerted beneficial effects on the blood flow (148+/-13%) for an extended
      period of time, inducing a significant change at 5 min after its application and
      the maximum blood flow of 172+/-23% at 120 min. The enhanced vaginal blood flow
      was maintained for up to 210 min and gradually returned to the baseline
      afterward. The results of Western immunoblotting study displayed differential
      expression of MAP kinases (ERK1/2 and JNK) upon NO treatment, clearly
      demonstrating that PKC is involved in the blood flow regulation process. There
      were no significant changes in cell viability in vaginal cells upon exposure to
      NO-releasing microparticles as compared with the control. The results of this
      work supported that NO-releasing microparticles could improve the vaginal blood
      flow without causing cytotoxic effects and PKC-MAP kinase modules are involved in
      the NO-induced blood flow regulation process.

PMID- 19857896
TI  - Introduction to the development of the ISPCAN child abuse screening tools.
AB  - The World Report on Children and Violence, (Pinheiro, 2006) was produced at the
      request of the UN Secretary General and the UN General Assembly. This report
      recommended improvement in research on child abuse. ISPCAN representatives took
      this charge and developed 3 new instruments. We describe this background and
      introduce three new measures designed to assess the incidence and prevalence of
      child abuse and neglect.

PMID- 19857897
TI  - ISPCAN Child Abuse Screening Tool Children's Version (ICAST-C): Instrument
      development and multi-national pilot testing.
AB  - OBJECTIVE: To develop a child victimization survey among a diverse group of child
      protection experts and examine the performance of the instrument through a set of
      international pilot studies. METHODS: The initial draft of the instrument was
      developed after input from scientists and practitioners representing 40
      countries. Volunteers from the larger group of scientists participating in the
      Delphi review of the ICAST P and R reviewed the ICAST C by email in 2 rounds
      resulting in a final instrument. The ICAST C was then translated and back
      translated into six languages and field tested in four countries using a
      convenience sample of 571 children 12-17 years of age selected from schools and
      classrooms to which the investigators had easy access. RESULTS: The final ICAST C
      Home has 38 items and the ICAST C Institution has 44 items. These items serve as
      screeners and positive endorsements are followed by queries for frequency and
      perpetrator. Half of respondents were boys (49%). Endorsement for various forms
      of victimization ranged from 0 to 51%. Many children report violence exposure
      (51%), physical victimization (55%), psychological victimization (66%), sexual
      victimization (18%), and neglect in their homes (37%) in the last year. High
      rates of physical victimization (57%), psychological victimization (59%), and
      sexual victimization (22%) were also reported in schools in the last year.
      Internal consistency was moderate to high (alpha between .685 and .855) and
      missing data low (less than 1.5% for all but one item). CONCLUSIONS: In pilot
      testing, the ICAST C identifies high rates of child victimization in all domains.
      Rates of missing data are low, and internal consistency is moderate to high.
      Pilot testing demonstrated the feasibility of using child self-report as one
      strategy to assess child victimization. PRACTICE IMPLICATIONS: The ICAST C is a
      multi-national, multi-lingual, consensus-based survey instrument. It is available
      in six languages for international research to estimate child victimization.
      Assessing the prevalence of child victimization is critical in understanding the
      scope of the problem, setting national and local priorities, and garnering
      support for program and policy development aimed at child protection.

PMID- 19857898
TI  - Antiproliferative effect and genotoxicity of novel synthesized palladium
      complexes with organoarsenic ligands.
AB  - Three new palladium complexes with general formula [PdCl(2)L(2)], where
      L=heterofunctional organoarsenic ligand: (2-isopropoxyphenyl)diphenylarsine (1),
      (2-methoxyphenyl)-diphenylarsine (2) and (2-hydroxyphenyl)diphenylarsine (3) have
      been synthesized and fully characterized, including X-ray crystallographic data.
      Their potential antitumor effect and genotoxicity have been studied as well. The
      viability test performed on human tumor (MLS) and normal (Hfl-1) cell lines
      indicates significant cytotoxicity of complexes, which is higher in tumor cells
      than in normal cells. The lethal doses are comparable with those of standard
      metal-based chemotherapeutical drugs (carboplatin and oxaliplatin). These
      palladium complexes exhibit a higher cytotoxicity against tumor cells as against
      normal cells in vitro. A new static cytometric method was developed and
      simultaneously the classic AnnexinV test was performed. Complex 2 has an
      important capacity to induce apoptosis in tumor cells. The apoptotic process is
      triggered due to the interaction of these complexes with secondary structure of
      DNA in treated cells. The alkaline single-cell gel assay shows that the level of
      DNA damages induced by compounds 2 and 3 are significantly higher in tumor cells
      as in normal cells. These studies shown that complexes 1, 2 and 3 have biologic
      activity, the effect of complex 2 being superior to its platinum analogues,
      attributable to its structure.

PMID- 19857899
TI  - Site-directed mutagenesis reveals a conservation of the copper-binding site and
      the crucial role of His24 in CopH from Cupriavidus metallidurans CH34.
AB  - CopH is a periplasmic copper-binding protein from Cupriavidus metallidurans CH34
      that contains two histidine residues. Both His24 and His26 contribute to the
      formation of two high-affinity copper-binding sites in wild-type CopH and are
      likely involved in a 2N2O coordination sphere in the equatorial plane. We have
      used site-directed mutagenesis, and a series of spectroscopic and calorimetric
      studies to further characterize the copper-binding sites in CopH. While His24
      plays a predominant role in copper affinity, one Cu-binding site was lost when
      either histidine residue was mutated. However, as shown by NMR and EPR, the
      mutation of the His residues does not affect the structural organization of the
      Cu-binding site nor the number of nitrogen ligands involved in copper ligation.
      In the absence of structural data, we propose a model that conciliates most of
      the spectroscopic data recorded during this study.

PMID- 19857900
TI  - Effects of glycodelins on functional competence of spermatozoa.
AB  - Glycodelin is a glycoprotein with 4 known glycoforms, namely glycodelin-S,
      glycodelin-A, glycodelin-F and glycodelin-C. The glycoforms are present in the
      female reproductive tract which the spermatozoa must pass through before
      fertilizing the oocyte. Thus the spermatozoa interact with each of these
      glycoforms in succession. The glycoforms have different effects on sperm
      function. Glycodelin-S in the seminal plasma suppresses albumin-induced
      cholesterol efflux from the spermatozoa and thereby regulates the initiation of
      capacitation. Glycodelin-A in the oviductal fluid suppresses extracellular signal
      regulated kinase making the spermatozoa more sensitive to zona pellucida-induced
      acrosome reaction. Follicular fluid glycodelin-F suppresses progesterone-induced
      acrosome reaction and prevents premature acrosome reaction. Glycodelin-A and
      glycodelin-F also inhibit spermatozoa-zona pellucida binding by interacting with
      sperm surface fucosyltransferase-5, which also binds to zona pellucida
      glycoproteins. The physiological implication of this phenomenon remains to be
      determined. The inhibitory activities of glycodelin-A and glycodelin-F on
      spermatozoa-zona pellucida binding is removed by glycodelin-C in the cumulus
      matrix. Glycodelin-C not only displaces sperm-bound glycodelin-A and glycodelin
      F, it also enhances spermatozoa-zona pellucida binding. These different
      biological activities of the glycodelin isoforms are determined by glycosylation
      of the proteins. Deglycosylation abolishes the binding and therefore the action
      of the glycodelins on spermatozoa. Knowledge of the mechanism of actions of
      glycodelins may enable development of novel strategies for fertility regulation.

PMID- 19857901
TI  - The biological significance of detergent-resistant membranes in spermatozoa.
AB  - As mammalian spermatozoa ascend the female reproductive tract, they acquire the
      ability to fertilize an oocyte via a complex cascade of biophysical and
      biochemical changes collectively know as 'capacitation'. In virtually all species
      studied, capacitation is accompanied by dramatic remodeling of the surface
      architecture, in order to render spermatozoa competent to recognize the oocyte
      and initiate fertilization. Although the fundamental mechanisms that underpin the
      dynamic redistribution of sperm surface proteins are poorly understood, recent
      evidence indicates that this process may be facilitated, at least in part, by
      specialized membrane microdomains or lipid rafts. This notion is consistent with
      numerous demonstrations that lipid rafts contain a number of putative zona
      pellucida receptors, undergo a marked capacitation-associated lateral migration
      to the apical region of the sperm head, and possess the ability to selectively
      bind to the zona pellucida of unfertilized, but not fertilized oocytes.
      Accordingly, this review aims to cover the latest insights into sperm lipid raft
      research and considers the evidence that these microdomains serve as platforms
      for the assembly of key recognition molecules on the sperm surface during
      capacitation.

PMID- 19857902
TI  - Cell-mediated immunity to HIV in the female reproductive tract.
AB  - The majority of HIV infections occur via sexual transmission across a mucosal
      barrier. In the case of male-to-female transmission, HIV-susceptible target cells
      are abundant in the ectocervix and vagina but are also present in the upper
      reproductive tract (endocervix and uterus). While the mechanisms of HIV
      transmission in the female reproductive tract are an active area of
      investigation, cell-mediated immune responses in reproductive tissues have not
      been thoroughly characterized. HIV-specific CD8+ T cells are present in
      reproductive tissues, to some extent mirroring populations present in the blood
      and gastrointestinal mucosa. Innate natural killer (NK) cells and regulatory T
      cells are also present in the genital tract. Furthermore, there is mounting
      evidence that the female reproductive tract may be uniquely susceptible to
      infection at specific times during the menstrual cycle, due to hormonal
      regulation of both innate and adaptive immune responses. This review provides an
      overview of recent findings on cell-mediated immunity to HIV in the female
      reproductive tract.

PMID- 19857903
TI  - The role of the local microenvironment in regulating susceptibility and immune
      responses to sexually transmitted viruses in the female genital tract.
AB  - Sexually transmitted viruses cause chronic infections that have serious long-term
      health consequences. Based on the evidence from clinical and epidemiological
      studies, women carry a disproportionately higher burden of sexually transmitted
      diseases. The reasons for this are not well understood and possibly relate to a
      variety of social, behavioral and economic factors. In addition to these factors
      there are biological reasons that contribute to the higher prevalence in women.
      In this context it is critical to focus on and understand the local
      microenvironment of the female genital tract, since the majority of viral
      infections in women occur by heterosexual transmission. The genital tract is also
      the target site for initiation and maintenance of protective immune responses
      that could prevent or eliminate viral infections. The epithelial cells of the
      genital tract provide the first line of defense against viral entry. The
      interactions between each sexually transmitted virus and the genital epithelium
      are distinct and determine the outcome of exposure. They are also influenced by a
      number of factors in the local genital milieu. Among these factors are the female
      sex hormones that regulate both the susceptibility as well as immune responses to
      viral infections in the genital tract. Better understanding of the interactions
      of viruses with the local environment in the female genital tract will lead to
      development of novel methods to prevent sexually transmitted infections as well
      as to enhance innate and adaptive immunity.

PMID- 19857904
TI  - Gene expression profile during ovarian folliculogenesis.
AB  - Assisted reproductive technologies have progressed significantly and have
      provided successful treatment for many infertile couples. However, more advanced
      technologies are required for severe infertility such as premature ovarian
      failure and ovarian impairment due to adjuvant therapy for cancer. Ovarian tissue
      cryopreservation followed by in vitro growth of isolated follicles is a feasible
      proposition for such patients. Close coordination of communication among follicle
      cells including oocytes, granulosa and theca cells is required for follicle
      growth. Crucial factors may regulate the gonadotropin-independent and -dependent
      follicle growth stages. To facilitate development of a culture system for early
      growing follicles, DNA microarray analysis of mouse ovaries recovered at 7, 10,
      13, 16 and 19 days of age was performed to identify factors required for the
      growth of early-stage follicles. These studies showed strong intensity of zona
      pellucida glycoproteins, bone morphogenic protein-15 (BMP-15) and growth
      differentiation factor (GDF-9) in 7 days old mice, which gradually declined in 19
      days old mice. KIT, KIT ligand, anti-mullerian hormone (AMH) and platelet-derived
      growth factor (PDGF), known as granulosa cell secreted factors, also showed
      relatively high expression. These studies will facilitate our understanding of
      the regulatory factors involved in folliculogenesis and thereby enable
      establishment of in vitro culture system for ovarian follicles.

PMID- 19857905
TI  - The regulatory role of thymic stromal lymphopoietin (TSLP) in maternal-fetal
      immune tolerance during early human pregnancy.
AB  - Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, and the functional
      TSLP receptor (TSLPR) consists of a common IL-7 receptor alpha chain (IL-7Ralpha)
      and TSLP-specific gamma receptor chain (TSLPR-gamma). It has been demonstrated
      that TSLP plays an important role in the Th2 bias and regulatory T cell expansion
      of immune response and tolerance. A successful pregnancy, especially in the early
      phase, demonstrates features of a Th2 immune response and requires CD4(+)Foxp3(+)
      regulatory T cell expansion. We have found recently that TSLP-instructed decidual
      dendritic cells (dDCs) promote decidual CD4(+) T cells to produce Th2-type
      cytokines including IL-10, which is believed to be a key player in maternal-fetal
      tolerance. Phenotypic analyses have shown that the expanded cells are mainly
      CD4(+) Th2 cells and Foxp3(+) regulatory T cells. Our findings show that
      trophoblasts secrete TSLP that is able to instruct the dDCs to induce CD4(+) Th2
      cell and Foxp3(+) regulatory T cell differentiation in decidual CD4(+) T cells.

PMID- 19857906
TI  - The role of mitochondrial proteins in sperm capacitation.
AB  - Spermatozoa deposited in the female reproductive tract need to undergo a
      multifaceted maturation process prior to fertilization termed "capacitation".
      This process is regulated by several proteins which are compartmentalized in
      discrete domains of the spermatozoon including the head, the mid-piece and the
      principal piece. Over the last decade many proteins involved in capacitation have
      been identified, such as proteins involved in the organization of the tail,
      proteins involved in signal transduction, chaperones, ion-channel proteins and
      mitochondria-associated proteins. This review focuses on the identity and
      function of mitochondrial proteins which undergo capacitation-dependent tyrosine
      phosphorylation in spermatozoa.

PMID- 19857907
TI  - Correlation of cytokine expression with rabies virus distribution in rabies
      encephalitis.
AB  - Rabies encephalitis is a significant health hazard, particularly in Asia. To
      understand the role of immune mechanisms and cytokines in rabies encephalitis, we
      performed a retrospective and prospective study on the autopsy material.
      Representative histopathological sections were studied and subjected to
      immunostaining for rabies virus antigen, TNF-alpha and IL-1beta.
      Immunohistochemistry for IL-1beta and TNF-alpha revealed expression of these
      cytokines in 96% of cases in microglial cells, macrophages and lymphocytes with a
      strong positive correlation between IL-1beta and TNF-alpha immunopositivity and
      degree of perivascular and parenchymal inflammation. In addition, expression of
      IL-1beta and TNF-alpha also correlated positively with each other. However there
      was no direct correlation of viral antigen load with grading of cytokine
      expression. These findings indicate that IL-1beta and TNF-alpha together may play
      an important role to coordinate the dramatic inflammatory response associated
      with the rabies-encephalopathy. They may serve as important targets for future
      therapy.

PMID- 19857908
TI  - Islamic legacy of cardiology: inspirations from the holy sources.

PMID- 19857909
TI  - Keeping the genie in the bottle: transgene biocontainment by excision in pollen.
AB  - Gene flow from transgenic plants is an environmental and regulatory concern.
      While biocontainment might be achieved using male sterility or transgenic
      mitigation tools, we believe that perhaps the optimal solution might be simply to
      remove transgenes from pollen. Male sterility might not be ideal for many
      pollinators, and might not be implementable using standardized genes. Transgenic
      mitigation might not be useful to control conspecific gene flow (e.g. crop to
      crop), and relies on competition and not biocontainment per se. Site-specific
      recombination systems could allow highly efficient excision of transgenes in
      pollen to eliminate, or at least minimize, unwanted transgene movement via pollen
      dispersal. There are other potential biotechnologies, such as zinc finger
      nucleases, that could be also used for transgene excision.

PMID- 19857910
TI  - Interventions to improve team effectiveness: a systematic review.
AB  - OBJECTIVES: To review the literature on interventions to improve team
      effectiveness and identify their 'evidence based'-level. METHODS: Major data
      bases (PubMed, Web of Science, PsycInfo and Cochrane Library) were systematically
      searched for all relevant papers. Inclusion criteria were: peer-reviewed papers,
      published in English between January 1990 and April 2008, which present
      empirically based studies focussing on interventions to improve team
      effectiveness in health care. A data abstraction form was developed to summarize
      each paper. The Grading of Recommendations, Assessment, Development, and
      Evaluation Scale was used to assess the level of empirical evidence. RESULTS:
      Forty-eight papers were included in this review. Three categories of
      interventions were identified: training, tools, and organisational interventions.
      Target groups were mostly multidisciplinary teams in acute care. The majority of
      the studies found a positive association between the intervention and non
      technical team skills. Most articles presented research with a low level of
      evidence. Positive results in combination with a moderate or high level of
      evidence were found for some specific interventions: Simulation training, Crew
      Resource Management training, Team-based training and projects on Continuous
      quality improvement. CONCLUSIONS: There are only some studies available with high
      quality evidence on interventions to improve team effectiveness. These studies
      show that team training can improve the effectiveness of multidisciplinary teams
      in acute (hospital) care.

PMID- 19857912
TI  - [Starting over].

PMID- 19857911
TI  - The role of polyamines in the regulation of the plasma membrane and the tonoplast
      proton pumps under salt stress.
AB  - Polyamine content (PAs) often changes in response to abiotic stresses. It was
      shown that the accumulation of PAs decreased in roots treated for 24h with 200 mM
      NaCl. The role of polyamines (putrescine - PUT, spermidine - SPD and spermine -
      SPM) in the modification of the plasma membrane(PM) H(+)-ATPase (EC 3.6.3.6) and
      the vacuolar(V) H(+)-ATPase (EC 3.6.3.14) activities in cucumber roots treated
      with NaCl was investigated. 24h treatment of seedlings with 50 microM PUT, SPD or
      SPM lowered the activities of proton pumps in both membranes. The decreased H(+)
      ATPase activity in plasma membranes isolated from the PA-treated roots was
      positively correlated with a lower level of PM-H(+)-ATPase CsHA3 transcript.
      However, transcript levels of PM-H(+)-ATPase CsHA2 and V-ATPase subunit A and c
      in roots treated with 50 microM PAs were similar to those in the control.
      Additionally, treatment of plants with salt markedly increased the activity of
      the PM- and V-H(+)-ATPases. However, exposure of plants to 20% PEG had no effect
      on these activities. These data suggest that, under salt stress conditions, the
      increase in H(+)-ATPase activities is caused mainly by the ionic component of
      salt stress. It seems that the main role of the PAs in the 24h salt-treated
      cucumber plants could be a result of their cationic character. The PA levels
      decreased when concentration of Na(+) increased, so action of PAs contributes to
      ionic equilibrium. Moreover, the decrease in the concentration of polyamines,
      which inhibit the PM-H(+)-ATPase and the V-H(+)-ATPase, at least under the
      studied conditions, seems to be beneficial. Thus, plants can increase salinity
      tolerance by modifying the biosynthesis of polyamines.

PMID- 19857913
TI  - Plutonium as a chronomarker in Australian and New Zealand sediments: a comparison
      with (137)Cs.
AB  - The construction of high resolution chronologies of sediment profiles
      corresponding to the last 50-100 years usually entails the measurement of fallout
      radionuclides (210)Pb and (137)Cs. The anthropogenic radionuclide, (137)Cs,
      originating from atmospheric nuclear weapons testing can provide an important
      "first appearance" horizon of known age (1954-1955), providing much-needed
      validation for the sometimes uncertain interpretations associated with (210)Pb
      geochronology. However, while (137)Cs usually provides a strong signal in
      sediment in the northern hemisphere, total fallout of (137)Cs in the southern
      hemisphere was only 25% that of the north and the low activities of (137)Cs seen
      in Australian and New Zealand sediments can make its horizon of first appearance
      somewhat arguable. Low (137)Cs fallout also limited the size of the 1963-1964
      fallout peak, a peak that is usually seen in northern hemisphere sediment
      profiles but is often difficult to discern south of the equator. This paper shows
      examples of the use of nuclear weapons fallout Pu as a chronomarker in sediment
      cores from Australia (3 sites) and New Zealand (1 site). The Pu profiles of five
      cores are examined and compared with the corresponding (137)Cs profiles and
      (210)Pb geochronologies. We find that Pu has significant advantages over (137)Cs,
      including greater measurement sensitivity using alpha spectrometry and mass
      spectrometric techniques compared to (137)Cs measurements by gamma spectrometry.
      Moreover, Pu provides additional chronomarkers associated with changes in the Pu
      isotopic composition of fallout during the 1950s and 1960s. In particular, the
      (238)Pu/(239+240)Pu activity ratio shows distinct shifts in the early 1950s and
      the mid to late 1960s, providing important known-age horizons in southern
      hemisphere sediments. For estuarine and near-shore sediments Pu sometimes has
      another significant advantage over (137)Cs due to its enrichment in bottom
      sediment relative to (137)Cs resulting from the more efficient scavenging of
      dissolved Pu in seawater by sediment particles.

PMID- 19857914
TI  - Aid to positioning of patients.

PMID- 19857915
TI  - An unusual cranial dislocation of the mandibular condyle.
AB  - We report an unusual case of a 20-year-old man who presented with a superolateral
      dislocation of the left condyle with intracranial penetration following a road
      traffic accident. Management included open reduction of the condyle, rigid
      intermaxillary fixation (IMF), and intensive jaw physiotherapy. One year after
      operation he had good functional outcome with an interincisal opening of 30mm.

PMID- 19857916
TI  - Fatigability of back extensor muscles and low back pain during pregnancy.
AB  - BACKGROUND: Back pain is the most frequently reported musculo-skeletal problem
      during pregnancy. High muscle fatigability has been associated with back pain in
      the general population. During pregnancy, the gradual increase in loads may have
      a training effect, increasing strength and endurance of back muscles. This
      adaptation however may be too slow, or insufficient to be significant in light of
      other changes during pregnancy. METHODS: Thirty-two pregnant women performed a
      fatigue test which consisted of maintaining a fixed load of 70 Nm for 60 s while
      the surface EMG of the longissimus lumborum and multifidus muscles were recorded
      bilaterally at 14, 24 and 34 weeks of pregnancy. The measure of fatigability was
      the highest absolute slope of the median frequency of the power spectrum of the
      EMG of the four muscles. Occurrence and severity of back pain were reported on
      questionnaires at 14, 19, 24, 29 and 34 weeks. Binomial logistic regressions
      between back pain occurrence and the median frequency slopes were calculated.
      FINDINGS: None of the five logistic analyses demonstrated an improvement of the
      one-predictor model over the constant-only model, which indicates that the degree
      of fatigability of back extensor muscles did not predict the occurrence of back
      pain in our sample. INTERPRETATION: Fatigability of back extensor muscles was not
      found to be a predictor of back pain during pregnancy. This result should be
      taken with caution due to the small number of participants and broad definition
      of back pain used, and should be confirmed by studies with a larger number of
      participants.

PMID- 19857917
TI  - Life course determinants of racial and ethnic disparities in functional health
      trajectories.
AB  - Previous research has documented racial/ethnic disparities in functional health
      trajectories in old age, though little work has investigated the relative
      contribution of early and later life insults in their genesis. This paper uses
      two-part latent curve models to investigate the life course determinants of
      racial/ethnic disparities in functional health trajectories in the USA. We find
      that blacks and Hispanics have both a greater probability of having any
      limitation at baseline and more limitations on average among those who have any.
      Over time, there is convergence in trajectories between Hispanics and non
      Hispanic whites, though the black-white gap remains constant. In addition, we
      find that disparities result from differential exposure to poor childhood health,
      early life socioeconomic deprivation, as well as adult health and socioeconomic
      attainment. However, the impact of childhood insults is largely mediated by more
      contemporaneous factors. We also find little evidence that the impact of life
      course factors varies across groups.

PMID- 19857918
TI  - The geography of patient safety: a topical analysis of sterility.
AB  - Many studies on patient safety are geared towards prevention of adverse events by
      eliminating causes of error. In this article, I argue that patient safety
      research needs to widen its analytical scope and include causes of strength as
      well. This change of focus enables me to ask other questions, like why don't
      things go wrong more often? Or, what is the significance of time and space for
      patient safety? The focal point of this article is on the spatial dimension of
      patient safety. To gain insight into the 'geography' of patient safety and
      perform a topical analysis, I will focus on one specific kind of space (sterile
      space), one specific medical procedure (insertion of an intravenous line) and one
      specific medical ward (neonatology). Based on ethnographic data from research in
      the Netherlands, I demonstrate how spatial arrangements produce sterility and how
      sterility work produces spatial orders at the same time. Detailed analysis shows
      how a sterile line insertion involves the convergence of spatially distributed
      resources, relocations of the field of activity, an assemblage of an
      infrastructure of attention, a specific compositional order of materials, and the
      scaling down of one's degree of mobility. Sterility, I will argue, turns out to
      be a product of spatial orderings. Simultaneously, sterility work generates
      particular spatial orders, like open and restricted areas, by producing buffers
      and boundaries. However, the spatial order of sterility intersects with the
      spatial order of other lines of activity. Insight into the normative structure of
      these co-existing spatial orders turns out to be crucial for patient safety. By
      analyzing processes of spatial fine-tuning in everyday practice, it becomes
      possible to identify spatial competences and circumstances that enable staff
      members to provide safe health care. As such, a topical analysis offers an
      alternative perspective of patient safety, one that takes into account its
      spatial dimension.

PMID- 19857919
TI  - Socioeconomic inequalities in health dynamics: a comparison of Britain and the
      United States.
AB  - Drawing on theory and research on the fundamental causes of health, the life
      course, and the welfare state, we investigate social inequalities in dynamic self
      rated health for working-aged Britons and Americans. We use data from the British
      Household Panel Survey and Panel Study of Income Dynamics (1990-2004) and a
      mixture latent Markov model to test a theoretical model of health as a discrete
      state that may remain stable or change over time. Our contributions are
      threefold. First, our finding of three distinctive types of health processes
      (stable good health, stable poor health, and a "mover" health trajectory)
      represents a more differentiated profile of long-term health than previously
      shown. Second, we characterize health trajectories in structural terms by
      suggesting who was more likely to experience what type of health trajectory.
      Third, our more differentiated picture of dynamic health leads to a more nuanced
      understanding of comparative health: Although the health advantage of Britons was
      confirmed, our results also indicate that they were more likely to experience
      health change. Moreover, the socioeconomic gradient in long-term health was
      steeper in the US, raising provocative questions about how state policies and
      practices may affect population health.

PMID- 19857920
TI  - Neural correlates of affective influence on choice.
AB  - Making the right choice depends crucially on the accurate valuation of the
      available options in the light of current needs and goals of an individual. Thus,
      the valuation of identical options can vary considerably with motivational
      context. The present study investigated the neural structures underlying context
      dependent evaluation. We instructed participants to choose from food menu items
      based on different criteria: on their anticipated taste or on ease of
      preparation. The aim of the manipulation was to assess which neural sites were
      activated during choice guided by incentive value, and which during choice based
      on a value-irrelevant criterion. To assess the impact of increased motivation,
      affect-guided choice and cognition-guided choice was compared during the sated
      and hungry states. During affective choice, we identified increased activity in
      structures representing primarily valuation and taste (medial prefrontal cortex,
      insula). During cognitive choice, structures showing increased activity included
      those implicated in suppression and conflict monitoring (lateral orbitofrontal
      cortex, anterior cingulate). Hunger influenced choice-related activity in the
      ventrolateral prefrontal cortex. Our results show that choice is associated with
      the use of distinct neural structures for the pursuit of different goals.

PMID- 19857921
TI  - Episodic encephalopathy due to an occult spinal vascular malformation complicated
      by superficial siderosis.
AB  - Superficial siderosis (SS) of the central nervous system is a rare condition
      caused by chronic subarachnoid hemorrhage. Clinical manifestations typically
      include sensorineural hearing loss and cerebellar ataxia. Recurrent episodic
      encephalopathy in the setting of SS has not been reported. We describe a unique
      case of SS in a 67-year-old man with an 8-year history of episodic encephalopathy
      associated with headache and vomiting. The patient also had a history of
      progressive dementia, ataxia, and myelopathy. A diagnosis of superficial
      siderosis was made after magnetic resonance gradient-echo images showed diffuse
      hemosiderin staining over the cerebellum and cerebral convexities. No
      intracerebral source of hemorrhage was identified. The patient therefore
      underwent gadolinium-enhanced spinal MRI which suggested a possible vascular
      malformation. A therapeutic laminectomy subsequently confirmed an arteriovenous
      fistula which was resected. In SS, there are often long delays between symptom
      onset and definitive diagnosis. Early identification is facilitated by magnetic
      resonance imaging with gradient-echo sequences. When no source of hemorrhage is
      identified intracranially, then total spinal cord imaging is indicated to assess
      for an occult source of hemorrhage as occurred in our case.

PMID- 19857922
TI  - A scheme for the classification of explosions in the chemical process industry.
AB  - All process industry accidents fall under three broad categories-fire, explosion,
      and toxic release. Of these fire is the most common, followed by explosions.
      Within these broad categories occur a large number of sub-categories, each
      depicting a specific sub-type of a fire/explosion/toxic release. But whereas
      clear and self-consistent sub-classifications exist for fires and toxic releases,
      the situation is not as clear vis a vis explosions. In this paper the
      inconsistencies and/or shortcomings associated with the classification of
      different types of explosions, which are seen even in otherwise highly authentic
      and useful reference books on process safety, are reviewed. In its context a new
      classification is attempted which may, hopefully, provide a frame-of-reference
      for the future.

PMID- 19857923
TI  - Effects of particle size of fiberglass-resin powder from PCBs on the properties
      and volatile behavior of phenolic molding compound.
AB  - Fiberglass-resin powder (FR powder), a mixture of resin powder and glass fibers
      reclaimed from pulverized waste printed circuit boards (PCBs), is used as a
      partial substitute of wood flour in the production of modified phenolic molding
      compound (MPMC). The results show that incorporation of FR powder into MPMC as a
      filler enhances the thermal stability represented by heat deflection temperature
      (HDT). MPMC with FR powder smaller than 0.07 mm shows better properties, with a
      flexural strength of 73 MPa, a charpy notched impact strength of 3.0 kJ/m(2), a
      HDT of 167 degrees C, and a dielectric strength of 3.7 MV/m, all of which meet
      the standard data. Thermogravimetric analysis shows that thermal degradation of
      MPMC mainly includes three steps, and over 55% weight loss of MPMC occurs between
      temperatures of 370 degrees C and 575 degrees C. Phenol is the main volatile
      compound released from molding powder during the production of molding product.
      After molding powder cures to molding product, low level of residual phenol is
      detected. All the results indicate that the MPMC can be used as a new type of
      molding compound.

PMID- 19857924
TI  - Characterization of acid tars.
AB  - Acid tars from the processing of petroleum and petrochemicals using sulfuric acid
      were characterized by gas chromatography/mass spectrometry (GC/MS), inductively
      coupled plasma/optical emission spectrometry (ICP/OES), differential scanning
      calorimetry (DSC), Fourier transform infrared (FTIR) spectrometry, and scanning
      electron microscopy/energy dispersive X-ray (SEM/EDX) micro-analysis. Leaching of
      contaminants from the acid tars in 48 h batch tests with distilled water at a
      liquid-to-solid ratio 10:1 was also studied. GC/MS results show that the samples
      contained aliphatic hydrocarbons, cyclic hydrocarbons, up to 12 of the 16 USEPA
      priority polycyclic aromatic hydrocarbons (PAHs), and numerous other organic
      groups, including organic acids (sulfonic acids, carboxylic acids and aromatic
      acids), phenyl, nitrile, amide, furans, thiophenes, pyrroles, and phthalates,
      many of which are toxic. Metals analysis shows that Pb was present in significant
      concentration. DSC results show different transition peaks in the studied
      samples, demonstrating their complexity and variability. FTIR analysis further
      confirmed the presence of the organic groups detected by GC/MS. The SEM/EDX micro
      analysis results provided insight on the surface characteristics of the samples
      and show that contaminants distribution was heterogeneous. The results provide
      useful data on the composition, complexity, and variability of acid tars;
      information which hitherto have been scarce in public domain.

PMID- 19857925
TI  - Electrochemical treatment of Orange II dye solution--use of aluminum sacrificial
      electrodes and floc characterization.
AB  - Electrocoagulation (EC) of Orange II dye in a flow through cell with aluminum as
      sacrificial electrodes was carried out under varying conditions of dye
      concentration, current density, flow rate, conductivity, and the initial pH of
      the solution in order to optimize the operating parameters for maximum benefits.
      Maximum removal efficiency of 94.5% was obtained at the following conditions: dye
      concentration=10 ppm, current density=160 A/m(2), initial pH 6.5, conductance=7.1
      mS/cm, flow rate=350 mL/min, and concentration of added NaCl=4.0 g/L of dye
      solution. The EC-floc was characterized using Fourier transform infrared
      spectroscopy, scanning electron microscopy/energy dispersive X-ray spectroscopy,
      and powder X-ray diffraction techniques. The removal mechanism has been proposed
      that is in compliance with the Pourbaix diagram, solubility curve of aluminum
      oxides/hydroxides, and physico-chemical properties of the EC-floc.

PMID- 19857926
TI  - Burn wounds and microorganisms.

PMID- 19857927
TI  - An easy and safe pattern graft for facial burns.

PMID- 19857928
TI  - Inhalation injury in southwest China--the evolution of care.
AB  - AIM: This study aims to review the changes in management of inhalation injury and
      the associated reduction in mortality over the past 2 decades. METHODS: The
      records of burn patients with inhalation injury hospitalised in our institute
      from 1986 to 2005 were retrospectively analysed. The incidence of inhalation
      injury and the associated mortality were analysed. Meanwhile, the relationship of
      inhalation injury with age, total burn area, tracheostomy intubation and
      mechanical ventilation were studied. RESULTS: The incidence of inhalation injury
      was 8.01% in the total 10 608 hospitalised burn patients during the 20 years
      surveyed. Inhalation injury was always associated with large-sized burn and was
      more common in adults. The incidence of tracheostomy and mechanical ventilation
      increased from 39.46 and 30.28% in the period from 1986 to 1995 to 70.12 and
      39.74% from 1996 to 2005, respectively. The overall mortality of inhalation
      injured burn patients was 15.88% compared with 0.82% of the non-inhalation group.
      The mortality of the burn patients with inhalation injury dropped from 25.29%
      during the first 10 years to 11.71% during the second decade (p<0.01). Mortality
      secondary to inhalation injury as the lead cause decreased from 14.56 to 6.29%
      (p<0.01). CONCLUSION: The care of inhalation injury has made significant progress
      over the past 2 decades. The early diagnosis of inhalation injury, early airway
      control and pulmonary function assistance with mechanical ventilation contribute
      to the reduction of mortality.

PMID- 19857929
TI  - Pre-existing psychiatric disorders, psychological reactions to stress and the
      recovery of burn survivors.
AB  - This study aimed to investigate whether previous findings from a small
      retrospective study could be replicated prospectively. The previous study showed
      that patients with an existing diagnosis of psychosis or depression, admitted to
      a burns service, had longer hospital stays and longer wound healing times when
      compared with controls matched for burn injury but without a pre-existing
      psychiatric condition [1]. In this study it was hypothesised that those patients
      without pre-existing psychiatric diagnosis, but with high levels of psychological
      distress after burn would also show a similar pattern of delayed recovery to
      those with a pre-existing psychiatric illness. In addition, we examined potential
      mechanisms for slowed recovery, including; adherence with treatment; delayed
      discharge on social grounds and psychological distress. It was hypothesised that
      patients with pre-existing psychiatric diagnosis would exhibit poorer adherence
      and delayed placement due to social reasons, compared to patients without pre
      existing psychiatric diagnoses. 107 consecutive admissions to a burns service
      over a seven-month period were included in the study. Psychiatric history and
      level of psychological distress post-burn were collected for all patients as part
      of routine psychological screening. Patients were compared on the following
      outcome variables: number of days spent in hospital and number of procedures
      required. 24% (n=27) were found to have a pre-existing psychiatric diagnosis.
      This group were also found to have significantly longer hospital stays (Mann
      Whitney U=585.50, p<0.01) and required more surgical procedures than the group
      without a psychiatric history (Mann-Whitney U=569.00, p=<0.001). The pattern of
      results for the group with high psychological distress but without pre-existing
      psychiatric diagnoses mirrored that of the group with pre-existing psychiatric
      diagnoses, suggesting that heightened psychological distress alone, has a
      significant delaying effect upon the rate of recovery (Kruskal-Wallis X=24.75,
      p<0.01). An exploratory model entering all the variables stepwise at the same
      stage identified poor adherence and delayed discharge issues as making
      significant contributions to the final model (r=0.81 adjusted r(2)=62.9, F (4,
      42)=20.48, p<0.001). In conclusion, this study supports the role of psychosocial
      factors, such as pre-existing psychiatric diagnosis and in hospital psychological
      distress, in contributing the recovery of survivors of burns. This suggests that
      identifying and working with these difficulties may impact not only on
      psychosocial, but also physical aspects of recovery.

PMID- 19857930
TI  - Proteomic change of peripheral lymphocytes from scald injury and Pseudomonas
      aeruginosa sepsis in rabbits.
AB  - BACKGROUND: Increased susceptibility to infection has been related to impairment
      of lymphocyte-regulated immune responses after severe burn. The aim of this study
      is to identify the differential expression of proteins in circulating lymphocytes
      from scald injury and Pseudomonas aeruginosa sepsis in rabbits to provide a basis
      for pathogenesis of burns and sepsis. METHODS: Rabbits were subjected to sham
      burn (A), 30% scald (B), A+bacterial challenge (C) or B+bacterial challenge (D).
      Bacterial challenge was inflicted by an injection of 2.0x10(8) CFU P. aeruginosa
      (ATCC27853) in the auricular vein 22 h after the burn procedure. The animals were
      sacrificed 24 h later. Lymphocytes were isolated, and the differential proteins
      in the lymphocytes from the experimental and control animals were identified by
      two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser
      desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), two of
      which were confirmed by Western blotting. RESULTS: Nineteen differential protein
      spots were found by 2-DE and 12 spots (11 proteins) were identified. Differential
      expression of peroxiredoxin and annexin I was validated by Western blotting.
      Among the identified proteins, the expression levels of cofilin, cyclophilin A,
      ubiquitin, nucleoside diphosphate kinase, glutamate dehydrogenase and annexin I
      were down-regulated in group B, excessively down-regulated in group D, but mildly
      in group C, and peroxiredoxin was up-regulated in groups B and D. CONCLUSIONS:
      Proteome changes in lymphocytes from P. aeruginosa sepsis in the scalded rabbits
      were revealed, which are related to immune suppression and the pathogenesis of
      sepsis after scald injury.

PMID- 19857932
TI  - Targeting both cartilage and subchondral bone might be an optimal strategy for
      osteoarthritis therapy.

PMID- 19857931
TI  - High susceptibility to chronic social stress is associated with a depression-like
      phenotype.
AB  - Chronic stress is a key risk factor for a variety of diseases, including
      depression. There is a large degree of individual variation in the ability to
      recover successfully from a chronic stress exposure, but the determinants of this
      individual stress susceptibility are still poorly understood. We recently
      developed a novel mouse paradigm for chronic social stress during adolescence,
      which closely mimics the human condition of chronic social stress in respect to
      construct, face and predictive validity. By applying this chronic stress model to
      a large number of animals we aimed at identifying individuals that are either
      resilient or vulnerable to the persistent effects of chronic social stress
      exposure. Animals showing markedly elevated basal corticosterone levels 5 weeks
      following the end of the stress paradigm were considered "vulnerable", whereas
      individuals recovering quickly and being indistinguishable from controls were
      classified as "resilient". Stress vulnerability was associated with an increased
      level of corticotropin-releasing hormone in the paraventricular nucleus,
      decreased hippocampal mineralocorticoid receptor expression as well as increased
      anxiety- and depression-like behavior compared to resilient and control animals.
      In summary, we show that by using a large cohort of animals it is possible to
      select individuals that are vulnerable or resilient to the lasting effects of
      chronic social stress. The vulnerable phenotype mimics many aspects of stress
      related human affective disorders and this may be used as a novel approach to
      study depression in an animal model, ultimately contributing to a better
      understanding and treatment of stress-related disorders.

PMID- 19857933
TI  - Clear cell meningioma with anaplastic features: case report and review of
      literature.
AB  - Clear cell meningioma (CCM) is an uncommon variant of meningioma, corresponding
      to WHO grade II. We present two cases of CCMs with anaplastic features in the
      intracranial and intraspinal region. The first case is a 65-year-old male who
      gradually developed changes in behavior over a period of 1 year. The second case
      is a 35-year-old female who presented with a 7-month history of posterior
      cervicothoracic pain and dysuria for 1 week. Magnetic resonance imaging revealed
      an intracranial lesion in the right frontal lobe in the male patient, and an
      intradural extramedullary lesion at C7 in the female patient. On histological
      examination, both tumors partly exhibited unusual anaplastic appearances with
      nuclear pleomorphism, high mitotic activity and necrosis, distinct from classical
      CCMs. Tumor cells were immunoreactive to epithelial membrane antigen (EMA) and
      vimentin, with a high MIB-1 index up to 40%. Total excision was performed. The
      male patient was found to have developed local recurrence and lateral ventricle
      metastasis 3 months after surgery. A diagnosis of CCM with anaplastic features
      was made (WHO grade III). Based on its aggressive behavior, we recommend
      postoperative adjuvant radiotherapy or chemotherapy even if total excision of the
      tumor has been performed, and MRI scans every 3-6 months during the first period
      of follow-up.

PMID- 19857934
TI  - Atypical 'HoBi'-like pestiviruses--recent findings and implications thereof.
AB  - In 2004, an atypical pestivirus named D32/00_'HoBi', isolated from foetal calf
      serum (FCS) originating from Brazil, was described (Schirrmeier et al., 2004). A
      few years later, a closely related virus (Th/04_KhonKaen) was detected in serum
      from a calf in Thailand, indicating that this group of atypical pestiviruses
      already is spread in cattle populations in various regions of the world. At the
      Friedrich-Loeffler-Institute, Insel Riems, Germany, FCS batches are regularly
      tested for pestivirus contamination, in general with positive PCR results, and in
      some cases the contaminants have been typed as 'HoBi'-like. At the National
      Veterinary Institute (SVA) in Uppsala, Sweden, a recent event with contaminated
      FCS ruined much of the ongoing cell culture work. From the FCS and the
      contaminated cells we were able to amplify and sequence nucleic acid from three
      different pestivirus strains, including BVDV-1, -2 and 'HoBi'-like; this in a
      commercial FCS that had been tested free from pestivirus by the manufacturer. In
      this short communication we review the current status of atypical 'HoBi'-like
      pestiviruses, describe recent findings and discuss the implications thereof.

PMID- 19857935
TI  - Classical swine fever: comparison of oronasal immunisation with CP7E2alf marker
      and C-strain vaccines in domestic pigs.
AB  - Effective oronasal vaccination against classical swine fever (CSF) is essential
      to achieve protection in wild boar. However the currently available live CSF
      vaccines, e.g. C-strain, do not allow serological differentiation between
      infected and vaccinated animals (DIVA). A modified live marker vaccine candidate
      (CP7E2alf) has been recently developed (Reimann et al., 2004). This communication
      reports the comparison of CP7E2alf and C-strain virus vaccines during 98 days
      following oronasal immunisation in domestic pigs. C-strain vaccine virus was
      consistently detected in tonsils of all (n=30) animals from 3 to 77 days post
      vaccination (dpv) and in blood (n=36) between 3 and 13dpv by CSFV-specific rRT
      PCR. CP7E2alf virus RNA was detected in 6 animals slaughtered between 4 and 63dpv
      by a BVDV-specific rRT-PCR. The chimeric virus was not detected in blood samples.
      As detected by CSFV E2-specific antibody ELISA and virus neutralisation tests,
      seroconversion first occurred at 11dpv in the C-strain vaccinated group and
      between 11 and 15dpv in the CP7E2alf vaccinated group. The serological response
      was still present at 98dpv. The CP7E2alf serological response remained negative
      using the CSFV E(rns) ELISA whereas seroconversion occurred in the C-strain
      vaccinated group. In conclusion, the primary replication site of CP7E2alf vaccine
      virus was found to be the tonsils as in the C-strain and virulent field strains.
      Persistence of CP7E2alf in the tonsils was also demonstrated up to 63dpv. Both
      vaccines showed immunogenicity after oronasal administration in domestic pigs. In
      contrast to the C-strain, CP7E2alf vaccine allowed the use of DIVA approaches in
      serological tests. This study confirms CP7E2alf as a promising marker vaccine
      candidate for oronasal vaccination programmes to control CSF in domestic pigs and
      wild boar.

PMID- 19857936
TI  - Head and neck liposarcomas: a 32 years experience.
AB  - OBJECTIVE: The aim of this review is to study natural history, presentation,
      treatment and prognosis of head and neck liposarcomas. METHODS: We carry a
      retrospective study about 15 patients diagnosed and treated in our department
      between 1969 and 2001. Therapeutic modalities included surgery, radiotherapy and
      chemotherapy. RESULTS: Tumors were mostly localized at the neck (4 cases) and the
      scalp (3 cases). Cervical lymphadenopathy was found in 1 case. Chest X-ray found
      showed metastases in 2 cases. Histological types of liposarcomas were the
      following: myxoid (5 cases), well differentiated (4 cases), pleomorphic (4
      cases), round cell (1 case) and dedifferentiated (1 case). Twelve patients
      underwent surgery. Complete excision was performed in 7 cases. In the other 5
      cases, exeresis was incomplete and 4 of them received postoperative radiotherapy.
      Three patients were not operated because of vascular involvement (1 case) or
      metastasis (2 cases), and they all received radiotherapy alone. After initial
      treatment, complete remission was achieved in 7 cases (46.7%). A recurrence
      occurred in 8 cases (53.3%). Two of these patients were reoperated and another
      one received chemotherapy. In the other 5 cases, the tumor was uncontrollable and
      no additional treatment has been proposed. Five-year survival rate was 87% for
      patients who underwent surgery alone, 75% for those who underwent surgery and
      postoperative radiotherapy, and 0% for those treated by radiotherapy alone.
      CONCLUSION: The mainstay of treatment of head and neck liposarcomas is surgical
      excision and the prognosis is largely determined by the histological grade and
      the clinical stage.

PMID- 19857937
TI  - Inflammatory pseudotumor of the parapharyngeal space: a case report.
AB  - Inflammatory pseudotumor is an idiopathic granuloma characterized by infiltrative
      proliferation of inflammatory cells and myofibroblastic cells, as well as locally
      aggressive features, clinically and radiologically mimicking a neoplastic
      process. The occurrence of inflammatory pseudotumor in the head and neck area is
      uncommon, especially in the parapharyngeal space. The case of a 54-year-old
      female with inflammatory pseudotumor of the parapharyngeal space is presented.
      The patient initially complained of hoarseness, dysarthria, aspiration, and
      hearing impairment. MRI disclosed an expansive soft mass in the parapharyngeal
      space encompassing the carotid arteries. Histopathologically, the lesions were
      composed of numerous plasma cells, lymphocytes, histiocytes, and spindle
      myofibroblastic cells, showing perineural infiltration of inflammatory cells. The
      patients' symptoms, including conductive hearing loss, improved dramatically with
      reduction in lesion size after corticosteroid treatment.

PMID- 19857938
TI  - Endoscopic treatment of intranasal glioma in an infant presenting with dyspnea.
AB  - Nasal gliomas are uncommon congenital lesions arising from abnormal embryonic
      development. Clinically, these masses are firm and uncompressible.
      Histologically, they are made up of astrocytes and neuroglial cells, embedded in
      fibrous and vascular connective tissue. Proper management of a nasal glioma
      requires a multidisciplinary approach including an otorhinolaryngologist,
      radiologist, and neurosurgeon. Radiological investigations such as computed
      tomography or magnetic resonance imaging should be performed to exclude
      intracranial extension. The mainstay of treatment is complete surgical
      extirpation to avoid recurrence. We report one case of nasal glioma in a Japanese
      infant presenting with dyspnea and cyanosis. Diagnostic and therapeutic options
      are discussed in light of the current literature.

PMID- 19857939
TI  - Emerging therapeutic options in fulminant invasive rhinocerebral mucormycosis.
AB  - OBJECTIVE: Five cases of rhinocerebral mucormycosis (RCM) with different courses
      of illness and outcomes also due to different therapeutical strategies including
      Posaconazole as a new therapeutic option are described. Predisposing conditions
      for RCM are diabetes mellitus and immunosuppression. Diagnosis is often delayed
      because patients complain about nonspecific symptoms of acute rhinosinusitis, and
      initial CT imaging is unimpressive. Progressive disease, however, leads to early
      orbital and cerebral invasion. Due to the lack of typical clinical signs,
      diagnosis relies on histopathology. Therapy consists of the management of
      predisposing factors, radical surgical intervention and systemic antifungal
      therapy. METHODS: We describe five cases of RCM with different comorbidities and
      outcomes. RESULTS: RCM remains a diagnostic and therapeutic challenge because it
      begins with nonspecific symptoms and ends as fulminant disease with high
      mortality. Here, systemic treatment with Posaconazole appears to be a more
      effective alternative to amphotericin. CONCLUSION: If a patient is suspected
      having RCM, improvement of predisposing diseases, radical surgical debridement
      and effective systemic antifungal therapy must be instituted immediately.

PMID- 19857940
TI  - Roseomonas aestuarii sp. nov., a bacteriochlorophyll-a containing
      alphaproteobacterium isolated from an estuarine habitat of India.
AB  - Two strains (JC17(T) and JC19a) of orange pigmented bacteria were isolated from
      an estuarine sample. Cells of both the strains were Gram-negative coccobacilli,
      non-motile, non-spore forming and strictly aerobic. Chemo-organoheterotrophy was
      the growth mode for both strains and was possible on a wide range of organic
      compounds. Strains were non-hemolytic and contained low levels of BChl-a and
      carotenoids. The fatty acids (>1.0%) comprised C(18:1)omega7c, C(16:1)omega7c/iso
      C(15:0)2OH, C(16:0), C(16:0) 3-OH, C(18:1)2OH, C(16:1)omega5c, and C(19:0)
      cycloomega8c. The genomic DNA G+C content of strain JC17(T) was 66.2mol%. A
      phylogenetic tree based on 16S rRNA gene sequence analysis showed that strains
      JC17(T) and JC19a had the highest similarity to members of the genus Roseomonas
      and were closely related to Roseomonas cervicalis CIP104027(T) (96.4%) and
      Roseomonas ludipueritiae CIP107418(T) (96.3%) of the family Acetobacteraceae
      within the class Alphaproteobacteria. Strains JC17(T) and JC19a shared 100% 16S
      rRNA gene sequence similarity, were phenotypically (morphological, physiological,
      biochemical characters) identical and had closely related genomes (85% DDH).
      Based on polyphasic taxonomic data, strain JC17(T) is classified as a novel
      species of the genus Roseomonas for which the name Roseomonas aestuarii sp. nov.
      is proposed. The type strain is JC17(T) (=CCUG 57456(T) =KCTC 22692(T)
      =NBRC105654(T)).

PMID- 19857941
TI  - Long-term survival after recurrent hepatocellular carcinoma in liver transplant
      patients: clinical patterns and outcome variables.
AB  - BACKGROUND: The objective of this trial was to analyze the clinical patterns and
      outcome variables of recurrent hepatocellular carcinoma (HCC) in liver transplant
      patients. PATIENTS AND METHODS: Sixty patients after liver transplantation (LT)
      for HCC were analyzed. All of them received initially a calcineurin-inhibitor
      based immunosuppressive regimen. Recurrent HCC was treated by surgical
      intervention, if eligible, or adjuvant therapies. Furthermore, patients were
      converted to a Sirolimus (SRL)-based immunosuppressive regimen after tumor
      relapse. The impact of clinical and histopathological variables on post
      recurrence survival was analyzed in uni- and multivariate analysis. RESULTS:
      Sixteen liver recipients developed HCC recurrence between 4 and 58 months
      (median: 23 months) post-LT. Sites of first tumor recurrence were lung (n = 5),
      liver (n = 4), bone (n = 4), cerebrum (n = 1), adrenal gland (n = 1) and
      peritoneum (n = 1). Seven patients were amenable for surgical resection, while 9
      patients were only suitable for adjuvant treatment (n = 4) or general medical
      support (n = 5). Median survival rate post-recurrence was 65 months (range: 12
      136 months) in patients amenable for surgical therapy, and 5 months (range: 1-52
      months) in patients unsuitable for surgical intervention (P = 0.01). Multivariate
      analysis identified late (>24 months) posttransplant tumor relapse (P = 0.039)
      and surgical therapy (P = 0.014) as independent predictors of long-term survival
      after tumor relapse. Five patients are tumour-free alive for a median of 65
      months after surgical resection of recurrent HCC and conversion to SRL.
      CONCLUSION: Liver transplant patients with HCC recurrence should be treated
      surgically, if eligible, since this is an independent predictor of long-term
      survival.

PMID- 19857942
TI  - Cardiac segmental analysis in left ventricular noncompaction: experience in a
      pediatric population.
AB  - BACKGROUND: Echocardiography has been used to diagnose and describe left
      ventricular noncompaction (LVNC). No other study has investigated LVNC using the
      16-segment model described by the American Heart Association and the American
      Society of Echocardiography in children, some of whom have congenital heart
      disease. Using the ratio of noncompaction to compaction, the authors analyzed the
      16 segments and determined if severity was correlated with poor outcomes in a
      pediatric population. METHODS: The 16-segment noncompaction/compaction ratio,
      shortening, and ejection fractions were measured retrospectively in all children
      with LVNC at a single institution from January 1, 2000, to June 30, 2008.
      RESULTS: Forty-four patients had LVNC, an incidence of 0.3% of laboratory
      admissions. Twenty-eight patients (64%) who remained alive were assigned to group
      1, and 16 patients (36%) who either died or were transplanted constituted group
      2. Group 2 had more patients with significant associated congenital heart disease
      than group 1 (50% vs 18%, P < .05). We found similar regions of involvement in
      the 16-segment model with sparing of basal segments and involvement of the
      midpapillary and apical regions (P < .001); however, patients in group 2 were
      noted to have more segments involved (6 vs 4, P < .05), lower shortening
      fractions (16% vs 29%, P < .001), and lower ejection fractions (24% vs 47%, P <
      .001). The ejection fraction was inversely related to the number of segments (r =
      -0.63, P < .01), suggesting that more noncompaction portends a worse outcome.
      CONCLUSIONS: In younger patients with noncompaction, poor outcomes such as low
      ejection fractions, death, and transplantation are related to the number of left
      ventricular segments involved. There is more associated congenital heart disease
      in the pediatric population, which carries a poorer prognosis than the disease
      reported in adult populations.

PMID- 19857943
TI  - Study of stretched polypropylene fibres by 1H pulsed and CW NMR spectroscopy.
AB  - A set of stretched isotactic polypropylene fibres prepared with the draw ratio
      lambda=4 at four different stretching temperatures was investigated by H1 pulsed
      relaxation NMR methods and CW NMR spectroscopy. We have studied the influence of
      the stretching temperature and draw ratio upon the changes of structure and
      molecular mobility. Some information on the influence of these conditions was
      obtained from CW NMR measurements by means of the temperature dependences of
      second moment M(2) and decomposition of NMR spectra into elementary components
      corresponding to the chains with different mobility. H1 CW NMR spectra were
      measured at two (14.1 and 10.5 MHz) Larmor frequencies in the temperature range
      200-420 K. An analysis of the experimental data shows that the stretching of the
      fibres at different temperature results in a change of molecular mobility. Spin
      lattice relaxation times in laboratory (T(1)) and rotating (T(1rho)) frames were
      also measured on the set of the fibres in the temperature range 239-423 K at 30
      MHz Larmor frequency employing a home made pulse spectrometer. In the rotating
      frame spin-lattice relaxation time measurements in the temperature range above
      278 K three relaxation times T(1rho) have been observed. The minima of the
      temperature dependences of the observed relaxation times reflect an alpha
      relaxation process in crystalline regions and beta-relaxation process related to
      a double glass transition in the non-crystalline regions of the studied fibres.

PMID- 19857944
TI  - Distribution of HDL-cholesterol and non-HDL-cholesterol in Brazilian children and
      adolescents--the Floripa study.
AB  - BACKGROUND AND AIMS: HDL-cholesterol (HDL-C) and non-HDL-cholesterol (nHDL-C) are
      involved in atherosclerosis. The aim of this study was to determine the
      distribution of HDL-C and nHDL-C and its association with cardiovascular and
      socio-cultural variables in a pediatric Brazilian sample. METHODS AND RESULTS:
      Children and adolescents from Florianopolis were randomly selected and a
      structured questionnaire was administered, a physical examination was performed
      and a blood sample was collected. Enzymatic and Direct methods in vitro were used
      to determine the total cholesterol and HDL-cholesterol levels. The associations
      among HDL-C and nHDL-C and the described variables were tested by odds ratio and
      logistic regression. A total of 1009 individuals were examined. Based on the
      Brazilian criteria, 23% were classified with low levels of HDL-C and 25% with
      high levels of non-HDL-C. After multivariate analysis there were significant
      associations among low HDL-C and high C-reactive protein (OR, 3.3; 95% CI, 2.1
      5.2), paternal tobacco use (OR, 1.5; 95% CI,1.1-2.1), and high triceps-to
      subscapular index (OR, 1.5; 95% CI, 1.1-2.2). There were also significant
      associations among high nHDL-C and high waist circumference (OR, 1.95; 95% CI,
      1.16-3.29), black skin color (OR, 1.78; 95% CI, 1.06-3.06), and high income (OR,
      1.48; 95% CI, 1.09-2.02). CONCLUSIONS: In this sample, low levels of HDL-C were
      associated with other clinical variables such as a centripetal fat pattern and C
      reactive protein, and n-HDL-C was associated with abdominal obesity, skin color
      and economic class.

PMID- 19857945
TI  - Bis(monoacylglycero)phosphate, a peculiar phospholipid to control the fate of
      cholesterol: Implications in pathology.
AB  - Bis(monoacylglycero)phosphate (BMP) is a structural isomer of
      phosphatidylglycerol that exhibits an unusual sn1:sn1' stereoconfiguration, based
      on the position of the phosphate moiety on its two glycerol units. Early works
      have underlined the high concentration of BMP in the lysosomal compartment,
      especially during some lysosomal storage disorders and drug-induced
      phospholipidosis. Despite numerous studies, both biosynthetic and degradative
      pathways of BMP remained not completely elucidated. More recently, BMP has been
      localized in the internal membranes of late endosomes where it forms specialized
      lipid domains. Its involvement in both dynamics and lipid/protein sorting
      functions of late endosomes has started to be documented, especially in the
      control of cellular cholesterol distribution. BMP also plays an important role in
      the late endosomal/lysosomal degradative pathway. Another peculiarity of BMP is
      to be naturally enriched in docosahexaenoic acid and/or to specifically
      incorporate this fatty acid compared to other polyunsaturated fatty acids, which
      may confer specific biophysical and functional properties to this phospholipid.
      This review summarizes and updates our knowledge on BMP with an emphasis on its
      possible implication in human health and diseases, especially in relation to
      cholesterol homeostasis.

PMID- 19857947
TI  - Constitutive model for municipal solid waste incorporating mechanical creep and
      biodegradation-induced compression.
AB  - A constitutive model is proposed to describe the stress-strain behavior of
      municipal solid waste (MSW) under loading using the critical state soil mechanics
      framework. The modified cam clay model is extended to incorporate the effects of
      mechanical creep and time dependent biodegradation to calculate total compression
      under loading. Model parameters are evaluated based on one-dimensional
      compression and triaxial consolidated undrained test series conducted on three
      types of MSW: (a) fresh MSW obtained from working phase of a landfill, (b)
      landfilled waste retrieved from a landfill after 1.5 years of degradation, and
      (c) synthetic MSW with controlled composition. The model captures the stress
      strain and pore water pressure response of these three types of MSW adequately.
      The model is useful for assessing the deformation and stability of landfills and
      any post-closure development structures located on landfills.

PMID- 19857948
TI  - An assessment of municipal solid waste compost quality produced in different
      cities of India in the perspective of developing quality control indices.
AB  - A study was conducted to investigate physico-chemical properties, fertilizing
      potential and heavy metal polluting potentials of municipal solid waste composts
      produced in 29 cities of the country. Results indicated that except a very few
      samples, all other samples have normal pH and EC. Organic matter as well as major
      nutrients N and P contents in MSW composts are generally low as compared to the
      composts prepared from rural wastes. Heavy metal contents in composts from bigger
      cities (>1 million population) were higher by about 86% for Zn, 155% for Cu, 194%
      for Cd, 105% for Pb, 43% for Ni and 132% for Cr as compared to those from smaller
      cities (<1 million population). Composts prepared from source separated biogenos
      wastes contained, on average, higher organic matter (by 57%), total N (by 77%)
      and total P (by 78%), but lower concentrations of heavy metals Zn (by 63%), Cu
      (by 78%), Cd (by 64%), Pb (by 84%), Ni (by 50%), and Cr (by 63%) as compared to
      those prepared from mixed wastes. Partial segregation at the site of composting
      did not improve quality of compost significantly in terms of fertilizing
      parameters and heavy metal contents. Majority of MSW composts did not conform to
      the quality control guideline of 'The Fertilizer (Control) Order 1985' in respect
      of total organic C, total P, total K as well as heavy metals Cu, Pb and Cr. In
      order to enable the relevant stakeholders to judge overall quality, a scheme has
      been proposed for the categorization of composts into different marketable
      classes (A, B, C, and D) and restricted use classes (RU-1, RU-2, and RU-3) on the
      basis their fertilizing potential and as well as potential for contaminating soil
      and food chain. Under the scheme, 'Fertilizing index' was calculated from the
      values of total organic C, N, P, K, C/N ratio and stability parameter, and 'Clean
      index' was calculated from the contents of heavy metals, taking the relative
      importance of each of the parameters into consideration. As per the scheme,
      majority of the compost samples did not belong to any classes and hence, have
      been found unsuitable for any kind of use. As per the regulatory limits of
      different countries, very few compost samples (prepared from source separated
      biogenos wastes) were found in marketable classes (A, B, C and D) and some
      samples (11-14) were found suitable only for some restricted use.

PMID- 19857949
TI  - Using a composite material containing waste tire powder and polypropylene fiber
      cut end to recover spilled oil.
AB  - The superior oil absorption capacity of recycled polypropylene (PP) fiber and
      waste tire powder were used to recover spilled engine oil. We used ASTM F726-99
      method to evaluate oil adsorbing capability of PP fiber and found it to have a
      large, rapid oil sorption capacity. However, its lack of elasticity dramatically
      limited that capacity after repeated use. Tire powder, which absorbs less oil
      more slowly, is more elastic than PP fiber and can be used repeatedly up to a
      hundred times without losing its oil adsorption capability. We combined PP fiber
      and tire powder to develop a composite material capable of recovering greater
      amounts of oil than any of its components. This composite can be use repeatedly
      for at least 100 times. Thus, the material cost for recovering 1 ton of spilled
      oil is about USD $0.03, making it very competitive on the market.

PMID- 19857946
TI  - Asthmatics and ex-smokers respond early, heavy smokers respond late to mailed
      surveys in Italy.
AB  - RATIONALE AND OBJECTIVES: Response to mailed epidemiological surveys has
      decreased in recent decades. Since subjects with respiratory symptoms are usually
      early responders to surveys performed in Southern Europe, this trend could bias
      prevalence estimates. The present study aimed at evaluating the impact of non
      response bias on prevalence estimates of respiratory symptoms and smoking habits.
      METHODS: In 9 centres, participating in the Italian Study on Asthma in Young
      Adults (ISAYA), random samples of people aged 20-45 years were administered a
      mailed questionnaire between 1998 and 2000. Non-responders were contacted again
      first by mail and then by phone. Cumulative response percentage was 30.5%, 52.4%
      and 72.7% (18,873/25,969), respectively, after the 1st, 2nd and 3rd contact.
      RESULTS: The prevalence of self-reported current asthma, asthma-like symptoms,
      and chronic cough/phlegm was more than halved from the first contact (5.6%,
      17.8%, 14.6% respectively) to the third contact (2.7%, 6.4%, 6.9%). This pattern
      was less pronounced when considering allergic rhinitis and past asthma, whose
      prevalence decreased, respectively, from 21.5% to 15.6% and from 3.5% to 2.6%. At
      the same time the proportion of current smokers increased from 29.2% to 38%,
      while the proportion of ex-smokers decreased from 16.5% to 10.1%. In a
      multinomial logistic model current asthma, asthma-like symptoms, chronic
      cough/phlegm and smoking habits, and to a lower extent past asthma and allergic
      rhinitis, were significant predictors of late response. CONCLUSIONS: In Italy
      when response percentage is low, the prevalence of current asthma, chronic
      cough/phlegm and ex-smokers is overestimated, while the proportion of current
      smokers is underestimated.

PMID- 19857950
TI  - Estimation of future outflows of e-waste in India.
AB  - The purpose of this study is to construct an approach and a methodology to
      estimate the future outflows of electronic waste (e-waste) in India.
      Consequently, the study utilizes a time-series multiple lifespan end-of-life
      model proposed by Peralta and Fontanos for estimating the current and future
      quantities of e-waste in India. The model estimates future e-waste generation
      quantities by modeling their usage and disposal. The present work considers two
      scenarios for the approximation of e-waste generation based on user preferences
      to store or to recycle the e-waste. This model will help formal recyclers in
      India to make strategic decisions in planning for appropriate recycling
      infrastructure and institutional capacity building. Also an extension of the
      model proposed by Peralta and Fontanos is developed with the objective of helping
      decision makers to conduct WEEE estimates under a variety of assumptions to suit
      their region of study. During 2007-2011, the total WEEE estimates will be around
      2.5 million metric tons which include waste from personal computers (PC),
      television, refrigerators and washing machines. During the said period, the waste
      from PC will account for 30% of total units of WEEE generated.

PMID- 19857951
TI  - Physico-chemical and biological treatment of MSW landfill leachate.
AB  - This paper analyses the evolution of the physico-chemical characteristics of the
      leachate from the Central Landfill of Asturias (Spain), which has been operating
      since 1986, as well as different treatment options. The organic pollutant load of
      the leachate, expressed as chemical oxygen demand (COD), reached maximum values
      during the first year of operation of the landfill (around 80,000 mg/L),
      gradually decreasing over subsequent years to less than 5000 mg/L. The
      concentration of ammonium, however, has not decreased, presenting values of up to
      2000 mg/L. When feasible, recirculation can greatly decrease the organic matter
      content of the leachate to values of 1500-1600 mg COD/L. Applying anaerobic
      treatment to leachates with a COD between 11,000 and 16,000 mg/L, removal
      efficiencies of 80-88% were obtained for organic loading rates of 7 kg COD/m3d.
      For leachates with lower COD (4000-6000 mg/L), the efficiency decreased to around
      60% for organic loading rates of 1 kg COD/m3d. Applying coagulation-flocculation
      with iron trichloride or with aluminium polychloride, it was possible to reduce
      the non-biodegradable organic matter by 73-62% when treating old landfill
      leachate (COD: 4800 mg/L, BOD5: 670 mg/L), also reducing turbidity and colour by
      more than 97%. It is likewise possible to reduce the non-biodegradable organic
      matter that remains after biological treatment by adsorption with activated
      carbon, although adsorption capacities are usually low (from 15 to 150 mg COD/g
      adsorbent). As regards ammonium nitrogen, this can be reduced to final effluent
      values of 5 mg/L by means of nitrification/denitrification and to values of 126
      mg/L by stripping at pH 12 and 48 h of stirring.

PMID- 19857952
TI  - Aptamer based surface enhanced Raman scattering detection of vasopressin using
      multilayer nanotube arrays.
AB  - Here we present an optofluidic surface enhanced Raman spectroscopy (SERS) device
      for on-chip detection of vasopressin using an aptamer based binding assay. To
      create the SERS-active substrate, densely packed, 200 nm diameter, metal nanotube
      arrays were fabricated using an anodized alumina nanoporous membrane as a
      template for shadow evaporation. We explore the use of both single layer Au
      structures and multilayer Au/Ag/Au structures and also demonstrate a facile
      technique for integrating the membranes with all polydimethylsiloxane (PDMS)
      microfluidic devices. Using the integrated device, we demonstrate a linear
      response in the main detection peak intensity to solution phase concentration and
      a limit of detection on the order of 5.2 microU/mL. This low limit of detection
      is obtained with device containing the multilayer SERS substrate which we show
      exhibits a stronger Raman enhancement while maintaining biocompatibility and ease
      or surface reactivity with the capture probe.

PMID- 19857953
TI  - One step immunochromatographic assay for the rapid detection of Alexandrium
      minutum.
AB  - Harmful algal blooms represent a major threat to marine production, and
      particularly to shellfish farming. Current methods for analyzing environmental
      samples are tedious and time consuming because they require taxonomists and
      animal experiments. New rapid detection methods, such as immunoassays, are sought
      for alerting purposes and for the study of algal ecodynamics in their natural
      environment. Alexandrium minutum, which causes paralytic shellfish poisoning,
      occurs with increasing frequency along European coasts. We have developed a one
      step immunochromatographic assay which is based on the principle of
      immunochromatographic analysis and involves the use of two distinct monoclonal
      antibodies directed against surface antigens of A. minutum. The primary specific
      antibody was conjugated with colloidal gold, and the secondary antibody (capture
      reagent) is immobilized on a strip of nitrocellulose membrane. We could
      demonstrate that whole algae are able to diffuse without restriction in the
      porous material. The assay time for this qualitative but highly specific assay
      was less than 15 min, suitable for rapid on-site testing.

PMID- 19857954
TI  - Inkjet printed and "doctor blade" TiO2 photodetectors for DNA biosensors.
AB  - A dye sensitized TiO(2) photodetector has been integrated with a DNA detection
      method based on non-cross-linking hybridization of DNA-functionalized gold
      nanoparticles, resulting in a disposable colorimetric biosensor. We present a new
      approach for the fabrication of dye sensitized TiO(2) photodetectors by an inkjet
      printing technique-a non-contact digital, additive, no mask and no vacuum
      patterning method, ideal for cost efficient mass production. The developed
      biosensor was compared against a dye sensitized photodetector fabricated by the
      traditional "doctor blade" method. Detection of gold nanoparticle aggregation was
      possible for concentrations as low as 1.0 nM for the "doctor blade" system, and
      1.5 nM for the inkjet printed photodetector. The demonstrated sensitivity limits
      of developed biosensors are comparable to those of spectrophotometric techniques
      (1.0 nM). Our results show that a difference higher than 17% by traditional
      photodetector and 6% by inkjet printed in the photoresponses for the
      complementary and non-complementary gold nanoprobe assays could be attained for a
      specific DNA sequence from Mycobacterium tuberculosis, the etiologic agent of
      human tuberculosis. The decrease of costs associated with molecular diagnostic
      provided by a platform such as the one presented here may prove of paramount
      importance in developing countries.

PMID- 19857955
TI  - Overcoming self-destruction in the pancreas.
AB  - Type 1 diabetes (T1D) is an autoimmune disease where insulin producing pancreatic
      beta cells are progressively destroyed. In the absence of a cure, exogenous
      insulin is given to maintain glucose homeostasis. Tolerogenic strategies to halt
      destruction and facilitate recovery of beta cells are being explored. This
      disease is under polygenic control; the identification of specific candidate
      pathways to target for drug discovery or corrective therapy would enhance
      therapeutic options. Whilst islet transplantation combined with immune
      suppression has shown some efficacy, the availability of beta cells restricts its
      general use. Differentiation protocols directing cultured stem cells into
      pancreatic tissue are under development. The availability of embryonic stem cells
      from a mouse model of T1D should facilitate dissection of the causes and
      progression of this disease.

PMID- 19857956
TI  - Socioeconomic factors associated with risk of upper aerodigestive tract cancer in
      Europe.
AB  - INTRODUCTION: In the European Union, there are 180,000 new cases of upper
      aerodigestive tract (UADT) cancer cases per year--more than half of whom will die
      of the disease. Socioeconomic inequalities in UADT cancer incidence are
      recognised across Europe. We aimed to assess the components of socioeconomic risk
      both independently and through their influence on the known behavioural risk
      factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A
      multicentre case-control study with 2198 cases of UADT cancer and 2141 controls
      from hospital and population sources was undertaken involving 14 centres from 10
      countries. Personal interviews collected information on demographics, lifetime
      occupation history, smoking, alcohol consumption and diet. Socioeconomic status
      was measured by education, occupational social class and unemployment. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional
      logistic regression. RESULTS: When controlling for age, sex and centre
      significantly increased risks for UADT cancer were observed for those with low
      versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for
      occupational socioeconomic indicators--comparing the lowest versus highest
      International Socio-Economic Index (ISEI) quartile for the longest occupation
      gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical
      significance remained for low education when adjusting for smoking, alcohol and
      diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities
      were observed only among men but not among women and were greater among those in
      the British Isles and Eastern European countries than in Southern and
      Central/Northern European countries. Associations were broadly consistent for
      subsite and source of controls (hospital and community). CONCLUSION:
      Socioeconomic inequalities for UADT cancers are only observed among men and are
      not totally explained by smoking, alcohol drinking and diet.

PMID- 19857957
TI  - Pegylated interferons: prospects for the use in the adjuvant and palliative
      therapy of metastatic melanoma.
AB  - Classic interferon-alpha formulations have antitumour activity in a variety of
      neoplastic diseases, including the adjuvant and palliative setting of metastatic
      melanoma, as single agents or in combination with chemotherapy and/or interleukin
      2. Pegylated interferon, widely used for the treatment of hepatitis, seems to be
      at least equally efficacious as standard recombinant interferon in the treatment
      of metastatic melanoma, and the available evidence suggests that equi-efficacious
      doses have somewhat lower acute toxicity. Moreover, the favourable
      pharmacokinetic properties of pegylated interferon allow the administration on a
      weekly basis, with sustained exposure to interferon during that entire period.
      Several clinical trials have been conducted testing adjuvant and palliative
      treatment with pegylated interferon-alpha in high-risk melanoma patients with
      promising results. The role of pegylated interferons in the setting of advanced
      metastatic melanoma will need further investigation in clinical trials,
      potentially in combination with targeted or cytotoxic agents with regard to
      synergistic antiangiogenic and cytotoxic effects. The use of pegylated
      interferons in earlier stage melanomas will be investigated in upcoming trials.

PMID- 19857958
TI  - Expression of NF-kappaB and IkappaB proteins in skeletal muscle of gastric cancer
      patients.
AB  - The mechanisms eliciting cancer cachexia are not well understood. Wasting of
      skeletal muscle is problematic because it is responsible for the clinical
      deterioration in cancer patients and for the ability to tolerate cancer
      treatment. Studies done on animals suggest that nuclear factor of kappa B (NF
      kappaB) signalling is important in the progression of muscle wasting due to
      several types of tumours. However, there are no published studies in humans on
      the role of NF-kappaB in cancer cachexia. In this project, we studied the rectus
      abdominis muscle in patients with gastric tumours (n=14) and in age-matched
      control subjects (n=10) for markers of NF-kappaB activation. Nuclear levels of
      p65, p50 and Bcl-3 were the same in both groups of subjects. However, phospho-p65
      was elevated by 25% in the muscles of cancer patients. In addition, expression of
      the inhibitor of kappa B alpha (IkappaBalpha) was decreased by 25% in cancer
      patients. Decreased expression of IkappaBalpha reflects its degradation by one of
      the IkappaBalpha kinases and is a marker of NF-kappaB activation. Interestingly,
      there was no correlation between the stage of cancer and the extent of
      IkappaBalpha decrease, nor was there a correlation between the degree of cachexia
      and decreased IkappaBalpha levels. This suggests that the activation of NF-kappaB
      is an early and sustained event in gastric cancer. The work implicates the NF
      kappaB signalling in the initiation and progression of cancer cachexia in humans
      and demonstrates the need for additional study of this pathway; it also
      recommends NF-kappaB signalling as a therapeutic target for the amelioration of
      cachexia as has been suggested from studies done on rodents.

PMID- 19857959
TI  - Three-stage hydrolysis to enhance enzymatic saccharification of steam-exploded
      corn stover.
AB  - The objective of the present research was to explore new approach to reduce the
      hydrolysis time and to enhance the productivity of enzymatic saccharification.
      One-stage hydrolysis of steam-exploded corn stover required 72 h to reach a yield
      of 62.8%, while multi-stage hydrolysis could reduce the time to 24 h. A concept
      of three-stage hydrolysis was therefore proposed in which cellulosic substrate
      was hydrolyzed for 6, 6, and 12 h, respectively. High hydrolysis yields, 70.2%
      with enzyme recycling and 76.1% with the supplement of fresh enzyme to eliminate
      enzyme recovery procedure, were obtained in 24 h. Analysis indicated that short
      time hydrolysis and the removal of end products at each stage improved cellulase
      activities and benefited the adsorption of cellulase enzyme to the solid
      substrate. When steam-exploded corn stover was used as the substrate for
      cellulase synthesis, a hydrolysis yield of 88.6% was achieved in 24 h.

PMID- 19857960
TI  - Performance of a three-stage membrane bioprocess treating the organic fraction of
      municipal solid waste and evolution of its archaeal and bacterial ecology.
AB  - A novel three-stage bioprocess achieved 75% volatile solids (VS) removal at an
      organic loading rate (OLR) of 4g VSL(-1)day, a solids retention time (SRT) of
      66days, a hydraulic retention time (HRT) of 20days, at a temperature of 35
      degrees C. The bioprocess consisted of an anaerobic hydrolytic reactor (HR) where
      the solids and liquid fractions of the Organic Fraction of the Municipal Solid
      Waste (OFMSW) were separated with a mesh. The leachate was pumped to a Submerged
      Anaerobic Membrane Bioreactor (SAMBR) and the treated permeate was polished in an
      Aerobic Membrane Bioreactor (AMBR). Denaturing Gradient Gel Electrophoresis
      (DGGE) and DNA sequencing analyses indicated that the increase in methane content
      in the HR caused by the excess sludge recycle from the SAMBR was associated with
      an increase in the number of hydrogenotrophic species, mainly Methanobrevibacter
      sp., Methanobacterium formicicum and Methanosarcina sp. At 20 degrees C VS
      removal dropped to 50% in the HR and some DGGE bands disappeared when compared to
      35 degrees C samples, while some bands such as the one corresponding to
      Ruminococcus flavefaciens were reduced in intensity. The species associated with
      the COD-polishing properties of the AMBR correspond to the genera Pseudomonas,
      Hyphomonas and Hyphomicrobiaceae. These results highlight the positive effect of
      recycling the excess sludge from the SAMBR to re-inoculate the HR with
      hydrogenotrophic species.

PMID- 19857961
TI  - Kraft pulp biobleaching using an extracellular enzymatic fluid produced by
      Pycnoporus sanguineus.
AB  - The aim of this work was to obtain a LMS pre-treatment applicable to industrial
      TCF bleaching. Kraft pulp from Eucalyptus globulus was treated at 40 degrees C/pH
      3 and 60 degrees C/pH 5 for 1h using an extracellular fluid enriched in laccase
      produced by Pycnoporus sanguineus and acetosyringone as mediator (HBT was used as
      a control mediator) (L). Alkaline extraction (E) and hydrogen peroxide (P) stages
      were then assayed. The LEP alternative was an efficient sequence to bleach kraft
      pulp since the enzymatic pre-treatment boosted the subsequent chemical bleaching.
      The best L pre-treatment was obtained with laccase-acetosyringone at 40 degrees
      C/pH 3. It reduces kappa number and hexenuronic acids, increases pulp viscosity,
      lowers hydrogen peroxide consumption down to an 87.4% (94.0% without L) and
      enhances brightness up to a 59% ISO (51% ISO without L).

PMID- 19857962
TI  - A fast predicting neural fuzzy model for on-line estimation of nutrient dynamics
      in an anoxic/oxic process.
AB  - In this paper a software sensor based on a fuzzy neural network approach was
      proposed for real-time estimation of nutrient concentrations. In order to improve
      the network performance, fuzzy subtractive clustering was used to identify model
      architecture, extract and optimize fuzzy rule of the model. A split network
      structure was applied separately for anaerobic and aerobic conditions was
      employed with dynamic modeling methods such as autoregressive with exogenous
      inputs and multi-way principal component analysis (MPCA). The proposed
      methodology was applied to a bench-scale anoxic/oxic process for biological
      nitrogen removal. The simulative results indicate that the learning ability and
      generalization of the model performed well and also worked well for normal batch
      operations corresponding to three data points inside the confidence limit
      determined by MPCA. Real-time estimation of NO(3)(-), NH(4)(+) and PO(4)(3-)
      concentration based on fuzzy neural network analysis were successfully carried
      out with the simple on-line information regarding the anoxic/oxic system.

PMID- 19857963
TI  - Synthesis of pyrrolo[2,3-d]pyrimidine derivatives and their antiproliferative
      activity against melanoma cell line.
AB  - Synthesis of a new series of diarylureas and amides having pyrrolo[2,3
      d]pyrimidine scaffold is described. Their in vitro antiproliferative activities
      against A375 human melanoma cell line and HS 27 fibroblast cell line were tested
      and the effect of substituents on pyrrolo[2,3-d]pyrimidine was investigated. The
      newly synthesized compounds, except N-acetyl derivatives (Id, Ie, and Im),
      generally showed superior or similar activity against A375 to Sorafenib. Among
      all of these derivatives, compounds Iq and Ir having imidazole and morpholine
      moieties, respectively, showed the most potent antiproliferative activity against
      A375.

PMID- 19857964
TI  - Structural basis for the inhibitor recognition of human Lyn kinase domain.
AB  - Human Lyn tyrosine kinase is expressed in hematopoietic tissues and plays crucial
      roles in the signal transduction of hematopoietic immune system. Its excess
      activity is involved in several tumors. The crystal structure has revealed that
      the potent inhibitor staurosporine binds to human Lyn kinase domain at the ATP
      binding site. The remarkable structural features of the staurosporine-binding
      region will offer valuable structural insights for the structure-based design of
      novel Lyn-selective inhibitors.

PMID- 19857965
TI  - Efficient conjugation of oligonucleotides through aromatic oxime formation.
AB  - The present work reports on the preparation of oligonucleotide conjugates via the
      formation of aromatic oxime linkage. The conjugation consists in the reaction
      between the oligonucleotide derivatized at 5'-extremity with a benzaldehyde
      moiety and an aminooxy reporter group. The conjugation was found highly efficient
      and was extended for the conjugation of phosphorothioate oligonucleotide. In
      addition, the stability of the so-formed oxime conjugate was investigated.

PMID- 19857966
TI  - Discovery of pyrazol-3-ylamino pyrazines as novel JAK2 inhibitors.
AB  - The design, synthesis and biological evaluation of a series of pyrazol-3-ylamino
      pyrazines as potent and selective JAK2 kinase inhibitors is reported, along with
      the pharmacokinetic and pharmacodynamic properties of lead compounds.

PMID- 19857967
TI  - 2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2.
AB  - Constitutive activation of the EPO/JAK2 signaling cascade has recently been
      implicated in a variety of myeloproliferative disorders including polycythemia
      vera, essential thrombocythemia and myelofibrosis. In an effort to uncover
      therapeutic potential of blocking the EPO/JAK2 signaling cascade, we sought to
      discover selective inhibitors that block the kinase activity of JAK2. Herein, we
      describe the discovery and structure based optimization of a novel series of 2
      amino-pyrazolo[1,5-a]pyrimidines that exhibit potent inhibition of JAK2.

PMID- 19857968
TI  - Antitumor antibiotic fostriecin covalently binds to cysteine-269 residue of
      protein phosphatase 2A catalytic subunit in mammalian cells.
AB  - Fostriecin is a phosphate monoester with excellent antitumor activity against
      mouse leukemia, and it is a potent inhibitor of protein phosphatase (PP) 2A. This
      compound has been predicted to covalently bind to the Cys269 residue of the PP2A
      catalytic subunit (PP2Ac) at the alpha,beta-unsaturated lactone via a conjugate
      addition reaction. However, this binding has not yet been experimentally proven.
      To confirm such binding, we synthesized biotin-labeled fostriecin (bio-Fos),
      which has an inhibitory activity against the proliferation of mouse leukemia
      cells. We showed that fostriecin directly binds to PP2Ac in HeLa S3 cells by pull
      down assays using bio-Fos. Moreover, we directly demonstrated that fostriecin
      covalently binds to the Cys269 residue of PP2Ac by matrix assisted laser
      desorption/ionization time-of-flight mass spectrometry analysis. From these
      results, the inhibitory mechanism of fostriecin on PP2A activity is discussed.

PMID- 19857969
TI  - Structural basis of the selectivity of the beta(2)-adrenergic receptor for
      fluorinated catecholamines.
AB  - The important and diverse biological functions of adrenergic receptors, a
      subclass of G protein-coupled receptors (GPCRs), have made the search for
      compounds that selectively stimulate or inhibit the activity of different
      adrenergic receptor subtypes an important area of medicinal chemistry. We
      previously synthesized 2-, 5-, and 6-fluoronorepinehprine (FNE) and 2-, 5-, and 6
      fluoroepinephrine (FEPI) and found that 2FNE and 2FEPI were selective beta
      adrenergic agonists and that 6FNE and 6FEPI were selective alpha-adrenergic
      agonists, while 5FNE and 5FEPI were unselective. Agonist potencies correlated
      well with receptor binding affinities. Here, through a combination of molecular
      modeling and site-directed mutagenesis, we have identified N293 in the beta(2)
      adrenergic receptor as a crucial residue for the selectivity of the receptor for
      catecholamines fluorinated at different positions.

PMID- 19857970
TI  - Theoretical calculations of a model of NOS indazole inhibitors: interaction of
      aromatic compounds with Zn-porphyrins.
AB  - We report a theoretical approach, at the M05-2x/6-311+G(d) level, to explain the
      affinity of indazoles for nitric oxide synthases using a simplified model of
      porphyrin. The theoretical E(rel)=E(i) stacking-E(i) apical values correlate with
      the experimental inhibition percents allowing to predict that 3,7-dinitro-1H
      indazole should be a good NOS inhibitor.

PMID- 19857971
TI  - Novel estrogen receptor (ER) modulators: carbamate and thiocarbamate derivatives
      with m-carborane bisphenol structure.
AB  - Novel carborane-containing estrogen receptor (ER) modulators, carbamate and
      thiocarbamate derivatives 5 and 6, were designed and synthesized based upon the m
      carborane bisphenol skeleton. Their activities were evaluated by competitive
      binding assay with recombinant human ERalpha, transcriptional activation assay
      and cell proliferation assay. All test compounds dose-dependently bound to human
      ERalpha and showed potent estrogenic activity. The binding affinities of
      thiocarbamates 6a and 6b are higher than those of the alkyl carbamates 5a-5d and
      are similar to that of the phenyl carbamate 5e. The binding affinity was well
      correlated with the acidity of the NH proton, indicating the existence of an
      interaction between the NH proton and amino acid residue(s) of the ERalpha ligand
      binding domain. The amino acid residue(s) interacting with the NH proton appears
      to be different from Asp351, which is known to play an important role in the
      expression of antiestrogenic activity. The side chain of the m-carborane
      bisphenol structure strictly controls the balance of estrogenic and
      antiestrogenic activities, and the (thio)carbamates can be classified as an
      agonist group.

PMID- 19857972
TI  - Gamma spectrometric measurements of depth-related radionuclide distribution in
      walls.
AB  - The method for depth-related radionuclide distribution was evolved for
      approximate determination of the spatial lay-out of radionuclides in materials.
      The method is based on different attenuation coefficients for various energies of
      gamma radiation. For each material, the attenuation coefficient decreases with
      rising energy of radiation. It is therefore possible to assess the location of
      radionuclides in a material owing to attenuation on the track which a photon has
      to pass through the material. In this case, gamma lines with energies 609 and
      1764 keV produced by nuclide (214)Bi were used for depth-related radionuclide
      distribution. This application should be suitable for locating radionuclides in
      the walls of buildings where high dose rates from gamma radiation occur. These
      doses are caused by natural radionuclides, mainly radium daughters. The presence
      of radionuclides in houses poses a high risk associated with inhalation of radon
      and its decay products. For suitable remediation, it is necessary to know the
      radionuclide depth distribution.

PMID- 19857973
TI  - Preliminary study of human breast tissue using synchrotron radiation combining
      WAXS and SAXS techniques.
AB  - Using synchrotron radiation, we combined simultaneously wide angle X-ray
      scattering (WAXS) and small angle X-ray scattering (SAXS) techniques to obtain
      the scattering profiles of normal and neoplastic breast tissues samples at the
      momentum transfer range 6.28 nm(-1)<or=Q(=4pi x sin(theta/2)/lambda)<or=50.26 nm(
      1) and 0.15 nm(-1)<or=Q<or=1.90 nm(-1), respectively. The results obtained show
      considerable differences between the scattering profiles of these tissues. We
      verified that the combination of some parameters (ratio between glandular and
      adipose peak intensity and third-order axial peak intensity) extracted from
      scattering profiles can be used for identifying breast cancer.

PMID- 19857974
TI  - Influence of Magnolol on the bystander effect induced by alpha-particle
      irradiation.
AB  - In this work, the influence of Magnolol on the bystander effect in alpha-particle
      irradiated Chinese hamster ovary (CHO) cells was examined. The bystander effect
      was studied through medium transfer experiments. Cytokinesis-block micronucleus
      (CBMN) assay was performed to quantify the chromosome damage induced by alpha
      particle irradiation. Our results showed that the alpha-particle induced
      micronuclei (MN) frequencies were suppressed with the presence of Magnolol.

PMID- 19857975
TI  - Chaperone-mediated autophagy: selectivity pays off.
AB  - Degradation of intracellular components in lysosomes, generically known as
      autophagy, can occur through different pathways. This review discusses chaperone
      mediated autophagy (CMA), a type of autophagy set apart from other autophagic
      pathways owing to its selectivity and distinctive mechanism by which substrates
      reach the lysosomal lumen. CMA participates in quality control and provides
      energy to cells under persistently poor nutritional conditions. Alterations in
      CMA have recently been shown to underlie some severe human disorders for which
      the decline with age in the activity of this pathway might become a major
      aggravating factor. Prevention of the age-dependent decline in CMA has major
      beneficial effects on cellular and organ homeostasis and function, revealing that
      CMA is an essential component of the anti-aging fight.

PMID- 19857976
TI  - The pharmacological chaperone effect of N-octyl-beta-valienamine on human mutant
      acid beta-glucosidases.
AB  - Gaucher's disease (GD), mainly caused by a defect of acid beta-glucosidase (beta
      Glu), is the most common form of sphingolipidosis. We have previously shown that
      the carbohydrate mimic and inhibitor of beta-Glu, N-octyl-beta-valienamine (NOV),
      could increase the protein level and enzyme activity of various mutant beta-Glus
      in cultured GD fibroblasts and in COS cells, suggesting that NOV acts as a
      pharmacological chaperone to accelerate transport and maturation of these mutant
      enzymes. In present study, we continued to investigate the chaperone
      characteristics of NOV. More importantly, chaperone activities of NOV were
      evaluated in COS cells transiently expressing ten new, recombinant beta-Glu
      mutants with mutations located in domain I, II and III. NOV was only effective on
      the T369M mutation, located in domain III. As we suggested in a previous study,
      domain III may be a prerequisite for pharmacological rescue of the mutant beta
      Glu by NOV. These characteristics of NOV could provide potential therapeutic
      chaperone properties that would be useful in the treatment of GD with
      neurological manifestations due to gene mutations in beta-Glu.

PMID- 19857977
TI  - Proton-detected heteronuclear single quantum correlation NMR spectroscopy in
      rigid solids with ultra-fast MAS.
AB  - In this article, we show the potential for utilizing proton-detected
      heteronuclear single quantum correlation (HSQC) NMR in rigid solids under ultra
      fast magic angle spinning (MAS) conditions. The indirect detection of carbon-13
      from coupled neighboring hydrogen nuclei provides a sensitivity enhancement of 3-
      to 4-fold in crystalline amino acids over direct-detected versions. Furthermore,
      the sensitivity enhancement is shown to be significantly larger for disordered
      solids that display inhomogeneously broadened carbon-13 spectra. Latrodectus
      hesperus (Black Widow) dragline silk is given as an example where the sample is
      mass-limited and the sensitivity enhancement for the proton-detected experiment
      is 8- to 13-fold. The ultra-fast MAS proton-detected HSQC solid-state NMR
      technique has the added advantage that no proton homonuclear decoupling is
      applied during the experiment. Further, well-resolved, indirectly observed carbon
      13 spectra can be obtained in some cases without heteronuclear proton decoupling.

PMID- 19857978
TI  - Time-of-flight remote detection MRI of thermally modified wood.
AB  - We demonstrate that time-of-flight (TOF) remote detection (RD) magnetic resonance
      imaging (MRI) provides detailed information about physical changes in wood due to
      thermal modification that is not available with conventional nuclear magnetic
      resonance (NMR) based techniques. In the experiments, xenon gas was forced to
      flow through Pinus sylvestris pine wood samples, and the flow paths and
      dispersion of gas atoms were observed by measuring (129)Xe TOF RD MRI images from
      the samples. MRI sensitivity of xenon was boosted by the spin exchange optical
      pumping (SEOP) method. Two different samples were studied: a reference sample,
      dried at low temperature, and a modified sample, which was thermally modified at
      240 degrees C after the drying. The samples were taken next to each other from
      the same wood plank in order to ensure the comparability of the results. The most
      important conclusion is that both the smaller dispersion observed in all the TOF
      RD experiments independent of each other and the decreased amount of flow paths
      shown by the time projection of z-encoded TOF RD MRI experiment imply that a
      large amount of pits connecting tracheid cells are closed in thermal
      modification. Closed pits may be one reason for reduced moisture content and
      improved dimensional stability of wood achieved in thermal modification. This is
      the first time biological samples have been investigated by TOF RD MRI.

PMID- 19857979
TI  - Electron spin relaxation of exchange coupled pairs of transition metal ions in
      solids. Ti2+-Ti2+ pairs and single Ti2+ ions in SrF2 crystals.
AB  - EPR (X- and Q-band) and electron spin relaxation measured by electron spin echo
      method (X-band) were studied for Ti(2+)(S=1) and Ti(2+)-Ti(2+) pairs in SrF(2)
      crystal at room temperature and in the temperature range 4.2-115 K. EPR spectrum
      consists of a strong line from Ti(2+) and quartets 2:3:3:2 from titanium pairs
      (S=2). Spin-Hamiltonian parameters of the pairs are g( parallel)=1.883, g(
      perpendicular)=1.975 and D=0.036 cm(-1). Temperature behavior of the dimer
      spectrum indicates ferromagnetic coupling between Ti(2+). Spin-lattice relaxation
      of individuals Ti(2+) is dominated by the ordinary two-phonon Raman process
      involving the whole phonon spectrum up to the Debye temperature Theta(D)=380 K
      with spin-phonon coupling parameter equal to 215 cm(-1). Important contribution
      to the relaxation arises from local mode vibrations of energy 133 cm(-1). The
      pair relaxation is faster due to the exchange coupling modulation mechanism with
      the relaxation rate characteristic for ferromagnetic ground state of the pairs
      1/T(1) is proportional to [exp(2J/kT)-1](-1) which allowed to estimate the
      exchange coupling J=36 cm(-1). The theories of electron-lattice relaxation
      governed by exchange interaction are outlined for extended spin systems, for
      clusters and for individual dimers. Electron spin echo decay is strongly
      modulated by coupling with surrounding (19)F nuclei. FT-spectrum of the
      modulations shows a dipolar splitting of the fluorine lines, which allows the
      evaluation of the off-center shift of Ti(2+) in pair as 0.132 nm. The electron
      spin echo dephasing is dominated by an instantaneous diffusion at low
      temperatures and by the spin-lattice relaxation processes above 18K.

PMID- 19857980
TI  - [Evaluation of family satisfaction of pediatrics emergency services].
AB  - OBJECTIVE: To determine the level of satisfaction of families of the pediatric
      department hospital emergency services; to identify the key service performance
      factors that could influence their final satisfaction and to find best practices
      from a review of experiences evaluated. METHODOLOGY: A descriptive retrospective
      study was carried out. Family members who accompanied a child during his stay in
      the hospital emergency service were included in the study. The sample was defined
      using a random systematic methodology with telephone surveys as the main tool.
      The statistical methods used were standard deviation for categorical variables
      and the analysis of the variance for the continuous variables. The SPSS 16.0
      programme was used as the main tool for evaluating the results. RESULTS: A total
      of 120 surveys were made with 96 responses obtained. The demographic profile of
      the main companion of the child was a woman, married, active worker with
      medium/university education. In 100% of the cases the main companion was a direct
      member of the family, and 85% of cases it was the child's mother. The pathology
      was considered mild in 65% of cases, with 86% of them being being resolved. There
      was very little difference between the actual time and the perceived time. From
      the information obtained, a high level of general satisfaction was perceived,
      with a positive assessment (in 76% of the cases), on the way the were treated by
      hospital staff. The areas for improvement were those associated with the
      identification of the health staff and facilities. CONCLUSION: As a general
      assessment of the study it was shown that the main factors of satisfaction for
      the family members were those related to being able to accompany the child, and
      the kindness and the respect.

PMID- 19857981
TI  - [Pre-hospital adverse events: a way to go].
AB  - BACKGROUND: The occurrence of adverse events is a problem at all levels of care
      and creates a significant burden of morbidity and mortality. In Spain there have
      been significant investigations of adverse effects (AE) in hospitals and primary
      care, however, studies of pre-hospital care are not yet developed. The aim of
      this study was to determine the frequency, type, preventability, severity and
      impact of "pre-hospital" adverse events, which were detected in the
      hospitalization index and the comparing those that occurred in ambulatory and non
      ambulatory care. METHOD: Case Series Study, with analytical components, of a
      sample of subjects included in the "National study of adverse events related to
      hospitalization (ENEAS). Qualitative data are presented as proportions with
      confidence intervals. For comparative analysis of qualitative data, we used the
      chi-square test. RESULTS: Of a total of 5624 patients, 2.3% (N=131) ((95%)CI:
      1.94-2.72) had an AE that occurred prior to hospitalization or "pre-hospital",
      and 40.5% of these (N=53) ((95%)CI: 32.05-48.86) were preventable. In 44 patients
      the AE had its origin in ambulatory care and 85 patients in non-ambulatory care.
      The characteristic of patients with ambulatory AE are men and older women (median
      76 years) who consulted for medical problems (84.1%) and the AE were related to
      medication in 77.8%. The characteristic of patients with non-ambulatory AE, were
      men (median 73 years), consulting for medical and surgical problems (44,7-55,3%)
      and the EA is related to medications, infections and procedures. CONCLUSIONS: The
      characteristics of patients with AE and undesirable effects that occurred during
      pre-hospitalization period depended on whether they originated during ambulatory
      care or non-ambulatory care. Therefore prevention strategies should take these
      differences into account.

PMID- 19857982
TI  - [Frequent attendance: primary care professional's perceptions of definitions,
      motives, situations and relationships with frequent attenders patients].
AB  - OBJECTIVE: To find out how health professionals in Primary Care (PC) perceive the
      definition criteria for frequent attendance, as well as their perceptions of the
      reasons for the visits of patients referred to as frequent attenders, their
      situations and their relationships with them. METHOD: We performed a qualitative
      study using semi-structured interviews in Primary Care centers of six health
      areas of the Community of Madrid. Eighteen interviews were conducted, three per
      area (two physicians and one nurse). Structural sampling was carried out with
      regards to the variables that could influence the discourse: health area,
      occupation, sex and number of years worked. The transcriptions were analyzed by
      two investigators who gave a consensus interpretation. RESULTS: The proportion of
      frequent attenders varies according to each professional and it is defined more
      by quality reasons than by number of visits. They make appointments associated
      with chronic diseases, but also for psychosocial or work problems. There are
      frequent attenders of all ages and both sexes, and the doctor-patient
      relationship depends on each individual case. CONCLUSIONS: Frequent attendance is
      defined by the professionals by a number of qualitative criteria in which the
      number of visits is of little importance. The reasons for consultation and
      patient characteristics are numerous, so a unique profile cannot be determined. A
      common factor in the discourses is that many of the frequent attenders' reasons
      for consultation were psychosocial problems, so streamlining coordination with
      psychosocial resources would help to make PC consultations more efficient and
      effective.

PMID- 19857983
TI  - [Quality management systems in drugs regulatory authorities: social impact].
AB  - The aim of this paper is to illustrate the social impact of drugs regulatory
      authorities' procedures, viewed from the perspective of the implementation of a
      quality management system. A review of drug regulations and their influence on
      quality and health systems is described.

PMID- 19857984
TI  - [The ethics review process in the Seventh Framework Programme of the European
      Commission].
AB  - The Seventh Framework Programme of the European Commission (EC) is one of the
      most important instruments for public funding of research and technological
      development. Besides the scientific assessment of each proposal, the ethical
      issues raised in them are evaluated in accordance with the current European
      legislation and the ethical principles laid down in the international
      declarations supported by Member States. Such ethical review is organized by the
      "Governance and Ethics" Unit (Directorate-General for Research), although it is
      done by professionals from different sectors and backgrounds who register
      themselves voluntary in a database.

PMID- 19857985
TI  - Light activation as a method of regulating and studying gene expression.
AB  - Recently, several advances have been made in the activation and deactivation of
      gene expression using light. These developments are based on the application of
      small molecule inducers of gene expression, antisense- or RNA interference
      mediated gene silencing, and the photochemical control of proteins regulating
      gene function. The majority of the examples employ a classical 'caging
      technology', through the chemical installation of a light-removable protecting
      group on the biological molecule (small molecule, oligonucleotide, or protein) of
      interest and rendering it inactive. UV light irradiation then removes the caging
      group and activates the molecule, enabling control over gene activity with high
      spatial and temporal resolution.

PMID- 19857986
TI  - How do ER export motifs work on ion channel trafficking?
AB  - The function of cells is strongly affected by the type and number of ion channels
      in the plasma membrane. Recent investigations have highlighted the complexity of
      the regulation of ion channel trafficking and uncovered several trafficking
      determinants including diacidic ER export motifs that influence surface
      expression of ion channels. The large number of ion channels for which functional
      diacidic motifs have already been identified underlines their general importance
      and has led to increasing research into the molecular function of these motifs.
      This review will summarize recent progress in identifying the molecular basis for
      recognition of ER export signals and the physiological relevance of regulated ER
      export of ion channels and its role in targeting of channel subunits.

PMID- 19857987
TI  - Plant developmental responses to the environment: eco-devo insights.
AB  - Evolutionary ecology and developmental biology have converged on the key insight
      that phenotypic expression is powerfully conditioned by environmental
      information. Plant ecological development (eco-devo) aims to firstly, determine
      precisely how plants perceive and respond to the varying environmental conditions
      they encounter in the real world and secondly, understand the ecological and
      evolutionary consequences of environmentally mediated phenotypic outcomes. This
      full explanatory scope, from molecular interactions to natural populations and
      communities, is just now being realized for two adaptively important aspects of
      developmental response: shade avoidance and flood tolerance. These and other new
      findings point to the complex, interactive nature of both environmental cues and
      gene-regulatory networks, and confirm the importance of incorporating realistic
      environmental variation into studies of development.

PMID- 19857988
TI  - Solubility, spectroscopic properties and photostability of Rhein/cyclodextrin
      inclusion complex.
AB  - The host-guest interaction between Rhein (Rh)--an anthraquinonic drug
      characterized by low water solubility and recently considered for its potential
      antidiabetic and antitumoral activities other than for the well-established anti
      inflammatory properties--with cyclodextrins (CDs) was investigated using phase
      solubility diagrams. The typical A(L) phase-solubility profiles suggest the
      formation of the 1:1 inclusion complexes between Rh and the two CDs investigated,
      namely beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin and the resulting
      constant values of complex formation, K(c), were estimated. Due to the higher
      K(c) value, complex of Rhein with 2-hydroxypropyl-beta-cyclodextrin was chosen
      for further investigation. Characterization in solution of 2-hydroxypropyl-beta
      cyclodextrin/Rhein complex was achieved both by fluorescence and visible
      spectroscopic techniques. These results confirm the formation of inclusion
      complexes in solution and the 1:1 stoichiometry of the binary system. With
      respect to Rhein aqueous solution behavior, the inclusion complex appears to be
      able: (i) to enhance Rhein solubility; (ii) to control its neutral/anionic
      equilibrium; (iii) to affect both its electronic absorption and fluorescence
      spectra. Finally, the photostability of Rhein in the presence of cyclodextrins
      was evaluated.

PMID- 19857989
TI  - Spectral studies on the interaction of pinacyanol chloride with binary
      surfactants in aqueous medium.
AB  - Interaction of pinacyanol chloride (PIN) with pure and binary mixtures of
      cetyltrimethylammonium bromide (CTAB) and sodium deoxycholate (NaDC) was
      spectroscopically studied. Interaction of PIN with pure NaDC produced a blue
      shifted metachromatic band (at approximately 502 nm), which gradually shifted to
      higher wavelength region as the concentration of NaDC increased in the pre
      micellar stage. For CTAB only intensity of both the bands increased without any
      shift. Mixed surfactant systems behaved differently than the pure components.
      Absorbance of monomeric band with a slight red-shift, and a simultaneous decrease
      in the absorbance of dimeric band of PIN, were observed for all the combinations
      in the post-micellar region. PIN-micelle binding constant (K(b)) for pure as well
      as mixed was determined from spectral data using Benesi-Hildebrand equation.
      Using the idea of Regular Solution Theory, micellar aggregates were assumed to be
      predominant than other aggregated state, like vesicles. Aggregation number was
      determined by fluorescence quenching method. Spectral analyses were also done to
      evaluate CMC values. Rubinigh's model for Regular Solution Theory was employed to
      evaluate the interaction parameters and micellar composition. Strong synergistic
      interaction between the oppositely charged surfactants was noted. Bulkier nature
      of NaDC lowered down its access in mixed micellar system.

PMID- 19857991
TI  - The application of in situ mid-FTIR fibre-optic reflectance spectroscopy and GC
      MS analysis to monitor and evaluate painting cleaning.
AB  - The development of non-invasive methodologies and portable instrumentation for in
      situ studies has been subject to great research and development in recent years
      in the field of conservation science. Despite such interest, very few reported
      studies employ these versatile techniques in the monitoring of cleaning
      treatments. This paper describes the application of mid-FTIR fibre-optic
      reflectance spectroscopy to monitor and evaluate the cleaning treatment of an oil
      painting using the chelating agent, triammonium citrate, a task undertaken in
      close collaboration with the painting conservator. Results obtained on site
      verify the removal of calcium oxalate and an organic component from the surface
      of the painting, later identified as a terpenic varnish. The subsequent, in
      laboratory FTIR and GC-MS analysis of the cotton swabs employed during the
      cleaning treatment acts as an additional non-invasive manner to support the
      results obtained in situ by mid-FTIR spectroscopy and to better understand the
      mechanism of the chosen cleaning agent.

PMID- 19857990
TI  - Study on the interaction of levocetirizine dihydrochloride with human serum
      albumin by molecular spectroscopy.
AB  - The interaction between cetirizine dihydrochloride and human serum albumin (HSA)
      has been examined by the spectroscopic techniques first. According to Stern
      Volmer equation at different temperatures and the UV-vis spectra examination it
      was demonstrated that HSA fluorescence quenching initiated by levocetirizine was
      static. The values of binding constant (K(A)) and the number of binding sites (n)
      for levocetirizine and HSA were smaller than those for cetirizine and HSA, which
      meant that the transport of drug was regulated by the stereoselectivity of HSA to
      the enantiomer. The effect of the non-enzymatic glycosylation (NEG) on the
      interaction between levocetirizine and HSA signified that the administration of
      levocetirizine for diabetes should be different from the normal. The positive
      DeltaS(o) and negative DeltaH(o) indicated that ionic interaction played a major
      role between levocetirizine and HSA. Circular dichroism (CD) measurement showed
      that the secondary structure of HSA has changed in the presence of
      levocetirizine, and alpha-helical content decreased from 63.1% for free HSA to
      54.9% for combined HSA, and accordingly the other secondary structure (beta
      strand, beta-turns and others) contents increased to some extent. Finally, by the
      competitive binding experiments it was deduced that levocetirizine specifically
      bound to HSA in the region of site II, which meant the curative effect of
      levocetirizine should be reconsidered when it was administrated together with
      other site II drugs.

PMID- 19857992
TI  - Paediatric HIV in central Sudan: high sero-prevalence and poor performance of
      clinical case definitions.
AB  - BACKGROUND: Paediatric clinical case definitions (CCDs) for the human
      immunodeficiency virus (HIV) have been proposed as screening tools in resource
      limited countries. OBJECTIVES: We assessed the performance of the World Health
      Organisation CCD (WHO-CCD), the Bloemfontein CCD (B-CCD) and a locally modified
      version of the Bloemfontein CCD (MB-CCD) in comparison with HIV serology in
      acutely hospitalised children aged 1.5-14 years. We also determined the HIV sero
      prevalence among this group of children. STUDY DESIGN: A cohort of 106
      consecutive acute paediatric admissions to a major teaching hospital in central
      Sudan was recruited over a 3-month period. RESULTS: The WHO-CCD, B-CCD, and MB
      CCD were relatively specific with estimates of 96.0% (95% confidence interval
      [CI] 90.1-98.9), 88.0% (95% CI 80.0-93.6), and 74.0% (95% CI 64.3-82.3),
      respectively. However, corresponding sensitivities were poor with estimates of
      16.7% (95% CI 0.4-64.1), 33.3% (95% CI 4.3-77.7), and 66.7% (95% CI 22.3-95.7),
      respectively. The HIV sero-prevalence was high at 5.7% (95% CI 2.1-11.9).
      CONCLUSIONS: CCDs performed poorly against HIV serology in acutely hospitalised
      children aged 1.5-14 years in central Sudan and, therefore, we advocate improving
      access to serological diagnostic tools. The high HIV sero-prevalence rate among
      this group of children poses serious challenges to policy makers and warrants
      further research.

PMID- 19857993
TI  - Evaluation of a rapid molecular algorithm for detection of pandemic influenza A
      (H1N1) 2009 virus and screening for a key oseltamivir resistance (H275Y)
      substitution in neuraminidase.
AB  - BACKGROUND: Rapid and specific molecular tests for identification of the recently
      identified pandemic influenza A/H1N1 2009 virus as well as rapid molecular tests
      to identify antiviral resistant strains are urgently needed. OBJECTIVES: We have
      evaluated the performance of two novel reverse transcriptase polymerase chain
      reactions (RT-PCRs) targeting specifically hemagglutinin and neuraminidase of
      pandemic influenza A/H1N1 virus in combination with a conserved matrix PCR. In
      addition, we investigated the performance of a novel discrimination RT-PCR for
      detection of the H275Y resistance mutation in the neuraminidase gene. STUDY
      DESIGN: Clinical performance of both subtype specific RT-PCR assays was evaluated
      through analysis of 684 throat swaps collected from individuals meeting the WHO
      case definition for the novel pandemic influenza virus. Analytical performance
      was analyzed through testing of 10-fold serial dilutions of RNA derived from the
      first Dutch sequenced and cultured confirmed case of novel pandemic influenza
      infection. Specificity and discriminative capacities of the H275Y discrimination
      assay were performed by testing wild type and recombinant H275Y pandemic
      influenza. RESULTS: 121 throat swaps collected from April 2009 to July 2009 were
      positive by at least two out of three RT-PCRs, and negative for the seasonal
      H3/H1 subtype specific RT-PCR assays. 117 of these were tested positive for all
      three (Ct-values from 15.1 to 36.8). No oseltamivir resistance was detected.
      CONCLUSIONS: We present a sensitive and specific approach for detection of
      pandemic influenza A/H1N1 2009 and a rapid RT-PCR assay detecting a primary
      oseltamivir resistance mutation which can be incorporated easily into clinical
      virology algorithms.

PMID- 19857994
TI  - Novel hepatitis B virus subgenotype A6 in African-Belgian patients.
AB  - BACKGROUND: Genome diversity of hepatitis B virus (HBV) is prominent among DNA
      viruses; which, allowed the virus to be genetically classified into eight
      genotypes and several subgenotypes. OBJECTIVE: To introduce and to characterize a
      novel subgenotype HBV, classified as A6. STUDY DESIGN: HBV full-length genomes
      were isolated and sequenced from three African-Belgian patients chronically
      infected with the virus. Using phylogenetic reconstruction and genetic distance
      calculation, the evolutionary relationships of the novel strains were
      investigated. RESULTS: Phylogenetic analysis based on complete genome sequences
      of genotype A strains revealed distinct clusters supported by high bootstrap
      values. The three African-Belgian strains clustered separately from the other
      known A subgenotypes (A1-A5) with maximal bootstrap support (100%). The mean
      inter-subgenotypic nucleotide divergence over the complete genome sequence
      between the novel A6 strains and A1-A5 was higher than 4%. CONCLUSION:
      Phylogenetic analysis of the complete genome sequences yielded maximal bootstrap
      value support for nodes that establish the new lineage as a novel subgenotype. In
      addition, nucleotide divergence more than 4% based on full-length genome of the
      virus, clearly demonstrated that the three African-Belgian strains belonged to a
      novel subgenotype of HBV, which was assigned as "A6". Noteworthy, the phylogeny
      of genotype A demonstrated that the A6 is a basal lineage that diverged earlier
      from the other African subgenotypes of genotype A.

PMID- 19857995
TI  - Sustained virological response in a patient with chronic hepatitis C treated by
      monotherapy with the NS3-4A protease inhibitor telaprevir.
AB  - Here, we describe for the first time a case of sustained virological response
      (SVR) achieved in a patient with chronic hepatitis C (CH-C) by monotherapy with a
      NS3-4A protease inhibitor, telaprevir, without interferon therapy. A 59-year-old
      treatment-naive Japanese man was enrolled in a phase II trial of telaprevir by
      repeat oral administration at a dose of 750mg every 8h for 24 weeks. At the start
      of treatment, he exhibited a low-level viremia with genotype 1b of the hepatitis
      C virus (HCV). After the first week of treatment with telaprevir, serum HCV RNA
      was undetectable, and negativity remained until the end of treatment. Moreover,
      he was evaluated as having a SVR after the post-treatment 24-week follow-up
      program. Two characteristics may explain the strong antiviral activity of
      telaprevir in the present case. First, although pre-treatment PCR-direct
      sequencing and cloning for the N-terminal in the NS3 region showed a protease
      inhibitor-resistant variant (T54A) in 1 of 32 independent clones, the T54A
      substitution has only a low-level resistance to protease inhibitors and his viral
      load was low. Second, when compared to a consequence sequence of 35 treatment
      naive patients with HCV genotype 1b, R130K and Q195K substitutions were unique to
      the present case. Although it is presently unknown whether the R130K and Q195K
      substitutions are related to SVR, this case suggests that long-term telaprevir
      monotherapy may be effective in CH-C patients with genotype 1 and a low viral
      load.

PMID- 19857997
TI  - New insights into mechanisms of gastrointestinal inflammation and cancer.

PMID- 19857998
TI  - Anti-haptoglobin antibody detection after febrile non-hemolytic transfusion
      reactions in a non-haptoglobin-deficient patient.

PMID- 19857999
TI  - Snodgrass hypospadias repair with onlay overlapping double-layered dorsal dartos
      flap without urethrocutaneous fistula: experience of 156 cases.
AB  - OBJECTIVE: To evaluate the neourethra covering created by a vascularized
      overlapping double-layered dorsal dartos flap for preventing urethrocutaneous
      fistula in the Snodgrass hypospadias repair (tubularized incised plate). PATIENTS
      AND METHODS: Between March 2003 and January 2008, 156 boys (mean age, 4.5 years)
      were enrolled for hypospadias repair. Preoperative position of the urethral
      meatus was subcoronal in 37, at the distal shaft in 61 and mid-shaft in 58 boys.
      All patients underwent the Snodgrass hypospadias repair. The neourethra was then
      covered with an overlapping double-layered dorsal dartos flap before glans and
      skin closure. RESULTS: All 156 patients underwent successful reconstruction. With
      a mean follow up of 23 months (range 6-42), all boys had a satisfactory
      subjective cosmetic and functional result with a vertically oriented, slit-like
      meatus at the tip of the glans. No urethrocutaneous fistula or urethral stenosis
      occurred. CONCLUSION: As the neouretha covering is an integral part of the
      Snodgrass hypospadias repair, a dorsal well vascularized double-layered dartos
      flap is a good choice for preventing urethrocutaneous fistula formation.

PMID- 19857996
TI  - Cannabinoid-opioid interactions during neuropathic pain and analgesia.
AB  - Opiates and exogenous cannabinoids, both potent analgesics used for the treatment
      of patients with neuropathic pain, bind to and activate class A G-protein-coupled
      receptors (GPCRs). Several lines of evidence have recently suggested that opioid
      and cannabinoid receptors can functionally interact in the central nervous system
      (CNS). These interactions may be direct, such as through receptor
      heteromerization, or indirect, such as through signaling cross-talk that includes
      agonist-mediated release and/or synthesis of endogenous ligands that can activate
      downstream receptors. Interactions between opioid and cannabinoid receptors may
      mediate many of the behavioral phenomena associated with the use of these drugs,
      including the production of acute antinociception and the development of
      tolerance and cross-tolerance to the antinociceptive effects of opioid and
      cannabinoid-specific ligands. This review summarizes behavioral, anatomical, and
      molecular data characterizing these interactions during the development of
      neuropathic pain and during antinociceptive treatment with these drugs alone or
      in combination. These studies are critical for understanding how the receptor
      systems involved in pain relief are altered during acute or chronic pain, and for
      designing better antinociceptive drug therapies, such as the combined use of
      opioid and cannabinoid receptor agonists or selective activation of receptor
      heteromers, that directly target the altered neurophysiology of patients
      experiencing pain.

PMID- 19858000
TI  - Simultaneous determination of thiamphenicol, florfenicol and florfenicol amine in
      swine muscle by liquid chromatography-tandem mass spectrometry with
      immunoaffinity chromatography clean-up.
AB  - A rapid and sensitive liquid chromatography-electrospray ionization-tandem mass
      spectrometry (LC-ESI-MS/MS) method to quantify thiamphenicol (TAP), florfenicol
      (FF), and florfenicol amine (FFA) in swine muscle is described. An immunoaffinity
      chromatography (IAC) column based on polyclonal antibodies and protein A
      sepharose CL 4B was used to clean-up extracted samples. IAC optimized conditions
      were found that allowed the IAC to be reused for selective binding of TAP, FF,
      and FFA. The dynamic column capacity was more than 512ng/mL of gel after being
      used for 15 cycles. From fortified swine muscle samples at levels of 0.4-50ng/g,
      the average recoveries were 85.2-98.9% with intra- and inter-day variations less
      than 9.8% and 12.4%, respectively. The limit of quantitation ranged from 0.4 to
      4.0microg/kg.

PMID- 19858001
TI  - Protein purification involving a unique auto-cleavage feature of a repeated EAAAK
      peptide.
AB  - Protein purification generally requires many steps of column chromatography that
      typically involve ion-exchange, hydrophobic-interaction and gel-filtration
      separations. More sophisticated purification of protein might be achieved through
      an application of affinity binding on a functionalized gel such as a nickel
      column, glutathione-modified column, maltose-modified gel column or others. Of
      several drawbacks existing in these methods, fusion proteins are commonly
      obtained, protease digestion might be necessary to remove the fusion moiety; a
      costly gel is employed for affinity binding, etc. Here we report that an
      expression vector derived from pREST was constructed to compose the gene of the
      chitin-binding protein (CBP) and the nucleotide sequence of the (EAAAK)(5)
      peptide linker following restriction sites for target gene insertion. Fusion
      proteins were expressed with E. coli and purified with a chitin column. The
      (EAAAK)(5) linker is shown to possess a pH-dependent auto-cleavage feature. In
      the range pH 6-7, the target protein becomes automatically released from the
      fusion protein without proteolytic treatment. Although the mechanism of this auto
      cleavage property of an (EAAAK)(5) linker is unclear, this feature has been
      successfully employed for many cases of protein purification without the tag of a
      fusion protein.

PMID- 19858002
TI  - Fast determination of glutathione by capillary electrophoresis with fluorescence
      detection using beta-cyclodextrin as modifier.
AB  - A rapid analytical method was developed for the quantitative determination of
      glutathione (GSH) using capillary electrophoresis and fluorescence detection. A
      fluorescence derivatization reagent, naphthalene-2,3-dicarboxaldehyde (NDA) was
      successfully applied to label GSH. The optimal derivatization reaction was
      performed with 5.0 mM NDA, 20 mM borate buffer (pH 9.2) with the reaction time of
      4 min at room temperature. The capillary electrophoresis analysis of GSH could be
      achieved in less than 120 s using 10 mM sodium tetraborate (pH 9.2) containing
      2.5 mM beta-cyclodextrin (beta-CD) as the running buffer, and the detection limit
      of 2.5 x 10(-9) M (S/N=3) was obtained. This method was successfully applied to
      analyze the content of GSH in tobacco BY-2 cells.

PMID- 19858003
TI  - Topoisomerase IIalpha-dependent induction of a persistent DNA damage response in
      response to transient etoposide exposure.
AB  - Cytotoxicity of the topoisomerase II (topoII) poison etoposide has been ascribed
      to the persistent covalent trapping of topoII in DNA cleavage complexes that
      become lethal as cells replicate their DNA. However, short term etoposide
      treatment also leads to subsequent cell death, suggesting that the lesions that
      lead to cytotoxicity arise rapidly and prior to the onset DNA replication. In the
      present study 1h treatment with 25muM etoposide was highly toxic and initiated a
      double-stranded DNA damage response as reflected by the recruitment of ATM, MDC1
      and DNA-PKcs to gammaH2AX foci. While most DNA breaks were rapidly repaired upon
      withdrawal of the etoposide treatment, the repair machinery remained engaged in
      foci for at least 24h following withdrawal. TopoII siRNA ablation showed the
      etoposide toxicity and gammaH2AX response to correlate with the inability of the
      cell to correct topoIIalpha-initiated DNA damage. gammaH2AX induction was
      resistant to the inhibition of DNA replication and transcription, but was
      increased by pre-treatment with the histone deacetylase inhibitor trichostatin A.
      These results link the lethality of etoposide to the generation of persistent
      topoIIalpha-dependent DNA defects within topologically open chromatin domains.

PMID- 19858004
TI  - Reconstruction of the exenterated orbit with osseointegrated implants.
AB  - Osseointegrated implant-fixated prostheses are useful for the reconstruction of
      the exenterated orbit. They provide good cosmesis, and are comfortable and light
      weight for the patient to wear. A retrospective review was performed of a series
      of twenty patients who had undergone orbital exenterations from 2003 to 2006,
      including complex cases with extraorbital and transcranial tumour excisions,
      nineteen of which were reconstructed with osseointegrated implant-fixated
      prostheses. For a successful outcome, decisions need to be made regarding the
      reconstruction of the orbital rim, periorbital soft tissues, indications for
      socket reconstruction and decisions regarding both one or two stage implantation
      and radiotherapy planning. Osseointegrated implants provide the optimal cosmetic
      and functional results in the rehabilitation of the exenterated orbit in our
      opinion. Close collaborative planning by both the surgeon and the prosthetist
      from the outset is essential.

PMID- 19858005
TI  - Outcomes of temporary self-expanding plastic stents (SEPS) use for
      gastrointestinal leaks. A case series.
AB  - INTRODUCTION: Gastrointestinal fistulas can develop as a complication of any
      gastrointestinal surgery, trauma, malignant disease, radiotherapy or because of
      iatrogenic procedures. The use of self expandable metallic stents (SEMS) has been
      reported as a feasible and effective therapeutic method. Self expandable plastic
      stents (SEPS) have been successfully used to treat esophageal malignancies,
      perforations and leaks but information regarding outcomes of SEPS in
      gastrointestinal leaks is scarce. OBJECTIVE: To report the outcomes and
      complications of endotherapy using SEPS in upper gastrointestinal tract fistulas
      following gastrointestinal surgery. MATERIAL AND METHODS: Retrospective review of
      5 cases of upper gastrointestinal leaks treated with SEPS. Medical records were
      reviewed to obtained patients demographics, procedure success, complications and
      follow up. RESULTS: We described 2 women and 3 men with an age ranged between 29
      and 65 years old. SEPS were left in place for a median period of 90 days (range:
      30-279 days). There were no complications related to SEPS placement, replacement
      or withdrawal. Fistulas closed in 60% of the cases where SEPS were the only
      therapeutic maneuver and in more than 80% when other therapy (cyanoacrilate,
      fibrin) was used. CONCLUSIONS: Endotherapy with SEPS appears as a feasible, safe
      and effective option for sealing gastrointestinal fistulas.

PMID- 19858006
TI  - [Self-perception, colonic transit and characteristics of subjects seeking medical
      care for constipation in Mexico.].
AB  - OBJECTIVES: Subjects seeking medical care for constipation were evaluated to find
      out: a) how they describe their complaint, b) their symptoms and colonic transit
      (CT) time, and c) determine what factors may allow to detect colonic inertia (CI)
      or obstructive defecation (OD). MATERIAL AND METHODS Patients demographics and
      medical history were collected and the modular Rome III questionnaire was
      applied. A screening CT with radioopaque markers was performed in all subjects.
      Those with an abnormal result underwent a multiple-pellet CT . Factors associated
      with CI and OD were analyzed. RESULTS: 105 patients were enrolled (92 females,
      mean age 36.7 years). Seventy patients described constipation as a bowel movement
      involving straining or being less frequently than expected (67%). The screening
      CT was normal in 79 patients (75%). Multiple-pellet CT was performed in 23
      patients (9 normal, CI in 6, OD in 8). Irritable bowel syndrome (IBS) criteria
      were met by 79 subjects (75%) and functional constipation by 26 (25%). A greater
      proportion of patients with CI or OD had attended the Emergency Room, used
      suppositories or enemas and interfered their activities due to constipation,
      during the previous year to the survey (p<0.05). CONCLUSIONS: Most patients
      described constipation as straining or lower frequency (67%) than expected. CT
      was normal in 84% of the patients, but it detected 6 cases of CI and 8 of OD.
      Patients that attended the Emergency Room, used suppositories or enemas and those
      whom activities were interfered turned out with CI or OD more frequently.

PMID- 19858007
TI  - [Anal intraepithelial neoplasia (NIA) and infection with human papillomavirus
      (HPV) in anoreceptive patients].
AB  - BACKGROUND: An association between human papilloma virus (HPV) infection and
      progression to anal intraepithelial neoplasia (AIN) and epidermoid cancer has
      been established. OBJECTIVE: To know the prevalence of low and high grade AIN, as
      well as HPV infection in an anoreceptive patients group, infected or not, by
      human immunodeficiency virus (HIV). MATERIAL AND METHODS: All patients with
      anoreceptive sexual relations were considered in this study. Patients who
      accepted anal citology and high definition anoscopy and biopsies with a follow-up
      not minor of 3 months were included. RESULTS: Forty-four patients were included:
      40 male (90.9%) with average age of 31 years. Anal cytology showed inflammatory
      alterations in 21 patients (28%), low grade intraepithelial lesion in 23 (52%);
      there were not patients with high grade epithelial lesion. According to the high
      definition anoscopy, there were low grade intraepithelial lesion in 42 patients
      (95%) and high grade in 2 (5%). Biopsy showed low grade intraepithelial in 26
      patients (59%), high grade in 4 (9%) and inflammatory alterations in 14 (32%).
      The prevalence of AIN and HPV infection was 68% in both diseases. The HIV
      infection was associated with the presence of high grade AIN (p=0.002, OR 47.7)
      CONCLUSIONS: There is a high prevalence of AIN and HPV infection between patients
      with anoreceptive sexual relations. The HIV infection is a risk factor for the
      development of high grade AIN.

PMID- 19858008
TI  - [Malnutrition in adults with gastrointestinal disorders: a new reservoir of
      celiac disease?].
AB  - INTRODUCTION AND OBJECTIVES: To present the diagnostic process of CD Celiac
      disease among adults showing variable signs of nutritional derangements assisted
      at two tertiary-level health care institutions in Havana City (Cuba) between 2004
      - 2007 for non-exhaustively characterized gastrointestinal disorders. MATERIAL
      AND METHOD: Clinical, serological, histo-pathological and nutritional findings
      were integrated into an ad hoc created scoring system. Weight gain was monitored
      during the study observation window. RESULTS: Twenty-eight presumptive celiac
      patients were identified among those assisted. CD diagnosis was as follows:
      Confirmed: 17.9% (Score: 9.2 +/- 0.4); Highly likely: 60.7% (Score: 6.6 +/- 1.1);
      Non-conclusive: 32.1% (Score: 4.7 +/- 0.5); respectively. Ninety-two point eight
      percent of subjects were malnourished at the moment of the first interview. Total
      intestinal villi atrophy was observed in less than one-third of the identified
      celiac patients. Tittering of antibodies associated with CD was as follows: Anti
      gliadin: Completed: 25; Positive: 72.0%; Anti-transglutaminase: Completed: 11;
      Positive: 54.5%. Nutritional replenishment actions comprised: Diet gluten
      withdrawal (100.0%); Vitamins and minerals prescription (92.9%); supplementary
      Enteral Nutrition (57.2%); and Parenteral Nutrition (21.4%). Weight gain was of
      400 grams in 80.8% of CD patients after 33.7 days of follow- up; and of 700 grams
      in 13 of them after 321 days. The scoring system presented in this study could be
      useful for diagnosis and treatment of CD: a condition that keeps baffling
      physicians and nutritionists alike.

PMID- 19858009
TI  - [Ablation of malignant liver tumors with radiofrequency. A series of cases in
      Mexico.].
AB  - BACKGROUND: Surgical resection is the treatment of choice for most of the primary
      and secondary liver tumors, unfortunately, many patients are not suitable for
      resection. Several ablative alternatives have been employed for treatment; the
      most commonly used has been radiofrequency ablation. OBJECTIVE: To establish the
      safety and results of treatment with radiofrequency ablation (RF) of malignant
      liver tumors. MATERIAL AND METHODS: A retrospective review of clinical files of
      patients with malignant hepatic tumors treated with RF was performed.
      Epidemiological variables, selection criteria pre- treatment and morbidity and
      mortality related to the procedure were analyzed. Descriptive statistics were
      used. RESULTS: From September 2002 to August 2006, 30 patients were treated:
      eighteen females and 12 males with a median age of 62 years (range 41-83 years).
      Histologic type was as follows: 18 hepatocellular carcinomas; 10 metastatic
      tumors (four breast, four colorectal and two neuro- endocrine); one gallbladder
      carcinoma and one peripheral cholangiocarcinoma. Indications for ablative
      procedure were the presence of cirrhosis, poor functional reserve, bilobar
      disease, proximity to major vascular structures and patients with increased
      operative risk. The size of the lesion range from 2 to 20 cm (mean 5.6 cm) and
      the median time of ablation was 30.2 min (range 5-50 min). Two minor
      complications (6.6%) and no operative mortality were recorded. At 18 months of
      follow-up, 23 patients (76.6%) are still alive and seven patients have died for
      tumor progression. CONCLUSION: Radiofrequency ablation is a safe procedure that
      allows local control of the disease with satisfactory results, when the surgical
      resection is not feasible.

PMID- 19858011
TI  - [Prevalence of neutropenic enterocolitis in adults with severe neutropenia and
      associated mortality.].
AB  - BACKGROUND: Neutropenic enterocolitis (NEC) is characterized by inflammatory
      damage and necrosis of the intestinal mucosa, mainly of the terminal ileum and
      the cecum. It is more frequent in patients with leukemia and/or undergoing
      antineoplastic chemotherapy, and the main risk factor is neutropenia <1000/mm3.
      OBJECTIVE: To know the prevalence of NEC and the mortality associated with it in
      adults with hematologic conditions and neutropenia <1000/mm3. MATERIAL AND
      METHODS: All adult patients who were hospitalized for malignant hematologic
      conditions with neutropenia <1000/mm3 were enrolled in the study; those with
      neutropenia >1000/mm3 were excluded. The diagnosis of NEC was based on the
      clinical data and imaging tests (abdominal plain X-rays and CT scan).
      Demographics of all patients were collected, as well as the data related with the
      course and treatment of the underlying hematologic condition and the NEC.
      RESULTS: 117 patients were enrolled in the study; 75.2% of them with some type of
      acute leukemia. The diagnosis of NEC was made in 8 patients (6.8%). NEC occurred
      in 10.5% of the patients with acute myeloid leukemia and in 8.0% of those with
      acute lymphocytic leukemia. Three patients died, which resulted in a 37.5%
      mortality rate. No association was found between the severity of neutropenia and
      the onset of NEC or NEC-related mortality. CONCLUSIONS: The prevalence of NEC in
      patients with hematologic conditions admitted for severe neutropenia is 6.8% and
      the mortality rate associated with this complication is 37.5%.

PMID- 19858010
TI  - Liver transplantation for neurologic Wilson's disease: reflections on two cases
      within a mexican cohort.
AB  - BACKGROUND: Liver transplantation (LT) in Wilson s disease (WD) is mostly
      indicated when progressing liver disease or acute liver failure occurs. In
      patients with neurological manifestations, this procedure has not gained wide
      acceptance based on previous reports of dismal prognosis. OBJECTIVE: To describe
      a Mexican cohort of pa- tients with WD with special focus on LT in patients with
      deteriorating neurological manifestations. MATERIAL AND METHODS: Patients with
      confirmed WD and their first-degree relatives were evaluated at the hepatology
      clinic of a tertiary referral hospital. Attention was placed on therapy and
      outcome. RESULTS: Eleven patients were followed for a period of up to 80 months
      (7 probands and 4 affected family members), 10 patients having hepatic
      manifestations and 4 having neuro psychia- tric phenomena. Pharmacologic
      treatment was uniform in most patients, and LT was indicated in 2 cases because
      of deteriorating neurological status. These patients had total remission of their
      neurological manifestations with marked improvement on imaging studies.
      CONCLUSIONS: Follow-up and pharmacologic treatment was flawed by several adverse
      conditions present in our population. Patients with progressing neurological
      disease had a favorable outcome after LT, a similar response to the one reported
      by several authors. In conclusion, LT should be strongly considered for the
      treatment of these patients.

PMID- 19858012
TI  - Serological markers in inflammatory bowel disease: a review of their clinical
      utility.
AB  - BACKGROUND: Several antibodies, also called serological markers, are associated
      with specific forms, disease behavior and phenotype of inflammatory bowel disease
      (IBD). AIM: Summarize and analyze the evidence of the utility of serologic
      markers in IBD, making emphasis on their clinical utility and behavior between
      populations. MATERIAL AND METHODS: Relevant articles were located by computer
      assisted search of PubMed (since January 1979 until December 2008). RESULTS: Anti
      Saccharomyces cerevisiae antibodies (ASCA) and perinuclear Anti-neutrophil
      Cytoplasmic Antibodies (pANCA) are the best studied serological markers.
      Assessing both ASCA and pANCA allows a better differentiation of Crohn's disease
      (CD) from ulcerative colitis (UC) than by using the individual tests alone. The
      ASCA+/pANCA- phenotype is characteristic of CD, while the ASCA-/pANCA+ phenotype
      is found in UC. The interest on atypical ANCA is growing as it may be a useful
      tool to distinguish between different IBD forms. Newer markers derived from
      various microbial species of the gut and glycan markers are of interest as they
      offer new ways to stratify patients into serologic subgroups. These serological
      markers may act as prognostic indicators of the severity and behavior of IBD, but
      more studies are necessary to determine their utility. CONCLUSIONS: There is
      emerging evidence that combining serological markers may increase the accuracy of
      diagnosis of a specific form of IBD or its behavior, but the perfect assay or
      combination of antibodies has not been discovered. They have several limitations,
      therefore clinicians must be aware of the evidence on serological markers,
      interpret them with caution and always correlate with the clinical picture.

PMID- 19858013
TI  - [Intermittent intestinal sub-occlusion secondary to Crohn's disease.].

PMID- 19858014
TI  - [Gastric stromal tumor (GIST), with clinical presentation of acute abdominal
      abscess.].

PMID- 19858015
TI  - [Idiopathic spontaneous hemoperitoneum.].
AB  - Intraperitoneal bleeding is common in patients with abdominal trauma or in those
      with benign gynecologic diseases, but it is very rare to occur spontaneously. The
      purpose of this communication is to report a female patient with idiopathic
      spontaneous hemoperitoneum (ISH). CASE PRESENTATION: A 28-year-old patient was
      admitted with 12-hour acute abdominal pain. Laboratory tests upon admission
      showed: Hb 9.0 g/dL, WBC 8.9 x 109/dL and negative immunologic pregnancy test.
      The ultrasound showed free intraperitoneal fluid. She underwent exploratory
      laparoscopy with findings of massive hemoperitoneum, which was resolved and,
      after a thorough exploration of the abdominal cavity, no evidence of the bleeding
      site was found. She was closely followed-up for 2 years without any recurrence or
      complications related to the ISH. An extensive review of the literature was
      performed. We conclude that ISH is a rare entity that usually presents as a
      surgical emergency and whose diagnosis is made in the absence of predisposing
      factors and excluding lesions in the abdominal blood vessels and organs. It
      warrants immediate intervention, which is crucial for patient survival.

PMID- 19858016
TI  - Ulcerative colitis in husband and wife. First report in Mexico.
AB  - The prevalence of inflammatory bowel disease in Mexico is low. The occurrence in
      familial cases has been attributed to genetic influences. We described the first
      report of inflammatory bowel diseases in one pairs of husband-wife in Mexico.
      According with characteristics of this case, we can speculate that the
      environmental and infectious etiology might play some role in the development of
      IBD.

PMID- 19858017
TI  - [Pelvic angiomyxoma. A case report from National Institute of Medical Sciences
      and Nutrition, Salvador Zubiran.].
AB  - An angiomyxoma is a pelvic neoplasia compound of myofibroblasts. This is a case
      report of a 41 years old female patient, who presented with a painful, pelvic
      mass, identified by a tomography with malignant characteristics. Total surgical
      excision was performed and coursed with good evolution time.

PMID- 19858018
TI  - [Gastric Schwannoma: a case report and literature review].
AB  - We report a 49-year old male with diagnosis of gastric schwannoma who underwent
      subtotal gastrectomy. We describe clinicopathological and immunohistochemical
      characteristics of these tumors and performed an extensive literature review.
      Gastric schwannomas are very rare tumors but they should be taken into account in
      the differential diagnosis of more common mesenchimal neoplasms like
      gastrointestinal stromal tumors (GIST). The treatment of choice is surgical
      resection and their prognosis is very favourable.

PMID- 19858019
TI  - [Hereditary non-polyposis colorectal cancer associated with hereditary gastric
      cancer. A case report.].
AB  - The information regarding the association of gastric cancer and type 2 Lynch
      syndrome is limited. Previous studies have reported that both entities may be
      present in the same individual in less than 5% of the cases. The most frequent
      form of hereditary colorectal cancer is the Lynch syndrome or Hereditary Non
      polyposic Colorectal Cancer, which is associated with germ-line mutation mostly
      of two genes, MLH1 and MSH2, which account for almost 90 percent of all
      identified mutations. The hereditary diffuse gastric cancer syndrome is caused by
      a germ-line mutation in the E-cadherin (CDH1) gene; only about 50 families with
      this syndrome have been reported. We present a case report of a patient who was
      diagnosed with both syndromes.

PMID- 19858020
TI  - [Sigmoid colon duplication: an adult case report.].
AB  - Colonic duplication is a very uncommon congenital malformation. Most cases are
      detected during childhood and may occur with other systemic malformations. Since
      1950, less than 90 cases of colonic duplication have been reported. In this
      study, we report the case of a 33-year-old female who was referred to our
      coloproctology service for evaluation. Since 16 years ago, she has noticed an
      intermittent left side painless abdominal mass that sometimes spontaneously
      disappears. In the last months, she reported that the frequency of this complaint
      has been more frequent. A barium enema X ray study revealed a significant
      dilation of the descendent and sigmoid colon. An exploratory laparotomy was
      performed and sigmoid colon duplication was found. The abnormal segment was
      removed and an end-to-end anastomosis was performed. There were no complications
      in the postoperative period and she was discharged at day 7. This case describes
      the difficulties in detecting this rare malformation that should be considered as
      part of the differential diagnosis of abdominal masses in adult patients.

PMID- 19858026
TI  - [Are they useful, prophylactic antibiotics in management of acute pancreatitis?].

PMID- 19858021
TI  - [Mexican consensus on the use of agents anti-TNF-alpha in the treatment of
      inflammatory bowel disease.].
AB  - BACKGROUND: Inflammatory bowel disease is a chronic and relapsing disorder
      without any curative medical treatment. Different drugs have been focused to get
      clinical remission during the flare, maintenance of remission and improving the
      quality of life of inflammatory bowel disease patients. Recently, new therapeutic
      agents blocking the tumoral necrosis factor alpha, a pro-inflammatory cytokine
      have been approved for the use in these kind of patients. OBJECTIVE: To establish
      the first Mexican Consensus for the use of anti tumoral necrosis factor alpha
      agents in the treatment of patients with inflammatory bowel disease. MATERIAL AND
      METHODS: A group of gastroenterologist and colorectal surgeons from different
      regions of the country were invited to attend to this meeting. The consensus was
      divided in 7 sections and a total of 53 items were evaluated for all
      participants. The Delphi system was used in this consensus and several clinical
      trials were considered in order to provide recommendations according to evidence
      based medicine. Finally, conclusions were obtained after discussing all items.
      RESULTS: This is the first mexican Consensus that provides the recommendations
      about the use of anti tumoral necrosis factor alpha agents in inflammatory bowel
      disease patients CONCLUSIONS: It is important to have a deep knowledge about the
      anti tumoral necrosis factor alpha in the following conditions: indications and
      contraindications; parameters of clinical efficacy; predicting factors of medical
      treatment response; strategies for preventing and treating immunogenicity;
      efficacy and safety as well as the clinical factors for using these agents as
      first line of therapy (top-down).

PMID- 19858027
TI  - Switching fuzzy dynamic output feedback H(infinity) control for nonlinear
      systems.
AB  - This paper studies the problem of dynamic output feedback H (infinity) control
      for nonlinear systems, which are described by Takagi-Sugeno fuzzy parts with
      measurable premise variables and uncertainty parts. The uncertainties are
      parameter dependent, unknown, and time varying but bounded. A switching fuzzy
      dynamic output feedback control scheme is proposed, which depends on the
      measurable premise variables and the bounds of the unknown parameters of the
      considered system, where the switching mechanism is introduced to handle the
      unknown parameters. A two-step linear-matrix-inequality-based optimization
      procedure is developed to design switching fuzzy H (infinity) controllers. An
      example is given to illustrate the effectiveness of the proposed design method.

PMID- 19858028
TI  - Globally exponential synchronization and synchronizability for general dynamical
      networks.
AB  - The globally exponential synchronization problem for general dynamical networks
      is considered in this paper. One quantity will be distilled from the coupling
      matrix to characterize the synchronizability of the corresponding dynamical
      networks. The calculation of such a quantity is very convenient even for large
      scale networks. The network topology is assumed to be directed and weakly
      connected, which implies that the coupling configuration matrix can be
      asymmetric, weighted, or reducible. This assumption is more consistent with the
      realistic network in practice than the constraint of symmetry and irreducibility.
      By using the Lyapunov functional method and the Kronecker product techniques,
      some criteria are obtained to guarantee the globally exponential synchronization
      of general dynamical networks. In addition, numerical examples, including small
      world and scale-free networks, are given to demonstrate the theoretical results.
      It will be shown that our criteria are available for large-scale dynamical
      networks.

PMID- 19858029
TI  - On the transient and steady-state estimates of interval genetic regulatory
      networks.
AB  - This paper is concerned with the transient and steady-state estimates of a class
      of genetic regulatory networks (GRNs). Some sufficient conditions, which do not
      only present the transient estimate but also provide the estimates of decay rate
      and decay coefficient of the GRN with interval parameter uncertainties (interval
      GRN), are established by means of linear matrix inequality (LMI) and Lyapunov
      Krasovskii functional. Moreover, the steady-state estimate of the proposed GRN
      model is also investigated. Furthermore, it is well known that gene regulation is
      an intrinsically noisy process due to intracellular and extracellular noise
      perturbations and environmental fluctuations. Then, by utilizing stochastic
      differential equation theory, the obtained results are extended to the case with
      noise perturbations due to natural random fluctuations. All the conditions are
      expressed within the framework of LMIs, which can easily be computed by using
      standard numerical software. A three-gene network is provided to illustrate the
      effectiveness of the theoretical results.

PMID- 19858030
TI  - Automated large-scale control of gene regulatory networks.
AB  - Controlling gene regulatory networks (GRNs) is an important and hard problem. As
      it is the case in all control problems, the curse of dimensionality is the main
      issue in real applications. It is possible that hundreds of genes may regulate
      one biological activity in an organism; this implies a huge state space, even in
      the case of Boolean models. This is also evident in the literature that shows
      that only models of small portions of the genome could be used in control
      applications. In this paper, we empower our framework for controlling GRNs by
      eliminating the need for expert knowledge to specify some crucial threshold that
      is necessary for producing effective results. Our framework is characterized by
      applying the factored Markov decision problem (FMDP) method to the control
      problem of GRNs. The FMDP is a suitable framework for large state spaces as it
      represents the probability distribution of state transitions using compact models
      so that more space and time efficient algorithms could be devised for solving
      control problems. We successfully mapped the GRN control problem to an FMDP and
      propose a model reduction algorithm that helps find approximate solutions for
      large networks by using existing FMDP solvers. The test results reported in this
      paper demonstrate the efficiency and effectiveness of the proposed approach.

PMID- 19858031
TI  - A multimodal interface device for online board games designed for sight-impaired
      people.
AB  - Online games between remote opponents playing over computer networks are becoming
      a common activity of everyday life. However, computer interfaces for board games
      are usually based on the visual channel. For example, they require players to
      check their moves on a video display and interact by using pointing devices such
      as a mouse. Hence, they are not suitable for visually impaired people. The
      present paper discusses a multipurpose system that allows especially blind and
      deafblind people playing chess or other board games over a network, therefore
      reducing their disability barrier. We describe and benchmark a prototype of a
      special interactive haptic device for online gaming providing a dual tactile
      feedback. The novel interface of this proposed device is able to guarantee not
      only a better game experience for everyone but also an improved quality of life
      for sight-impaired people.

PMID- 19858032
TI  - Experimental analysis of a mobile health system for mood disorders.
AB  - Depression is one of the leading causes of disability. Methods are needed to
      quantitatively classify emotions in order to better understand and treat mood
      disorders. This research proposes techniques to improve communication in body
      sensor network (BSN) that gathers data on the affective states of the patient.
      These BSNs can continuously monitor, discretely quantify, and classify a
      patient's depressive states. In addition, data on the patient's lifestyle can be
      correlated with his/her physiological conditions to identify how various stimuli
      trigger symptoms. This continuous stream of data is an improvement over a
      snapshot of localized symptoms that a doctor often collects during a medical
      examination. Our research first quantifies how the body interferes with
      communication in a BSN and detects a pattern between the line of sight of an
      embedded device and its reception rate. Then, a mathematical model of the data
      using linear programming techniques determines the optimal placement and number
      of sensors in a BSN to improve communication. Experimental results show that the
      optimal placement of embedded devices can reduce power cost up to 27% and reduce
      hardware costs up to 47%. This research brings researchers a step closer to
      continuous, real-time systemic monitoring that will allow one to analyze the
      dynamic human physiology and understand, diagnosis, and treat mood disorders.

PMID- 19858033
TI  - Emotion recognition from EEG using higher order crossings.
AB  - Electroencephalogram (EEG)-based emotion recognition is a relatively new field in
      the affective computing area with challenging issues regarding the induction of
      the emotional states and the extraction of the features in order to achieve
      optimum classification performance. In this paper, a novel emotion evocation and
      EEG-based feature extraction technique is presented. In particular, the mirror
      neuron system concept was adapted to efficiently foster emotion induction by the
      process of imitation. In addition, higher order crossings (HOC) analysis was
      employed for the feature extraction scheme and a robust classification method,
      namely HOC-emotion classifier (HOC-EC), was implemented testing four different
      classifiers [quadratic discriminant analysis (QDA), k-nearest neighbor,
      Mahalanobis distance, and support vector machines (SVMs)], in order to accomplish
      efficient emotion recognition. Through a series of facial expression image
      projection, EEG data have been collected by 16 healthy subjects using only 3 EEG
      channels, namely Fp1, Fp2, and a bipolar channel of F3 and F4 positions according
      to 10-20 system. Two scenarios were examined using EEG data from a single-channel
      and from combined-channels, respectively. Compared with other feature extraction
      methods, HOC-EC appears to outperform them, achieving a 62.3% (using QDA) and
      83.33% (using SVM) classification accuracy for the single-channel and combined
      channel cases, respectively, differentiating among the six basic emotions, i.e.,
      happiness, surprise, anger, fear, disgust, and sadness. As the emotion class-set
      reduces its dimension, the HOC-EC converges toward maximum classification rate
      (100% for five or less emotions), justifying the efficiency of the proposed
      approach. This could facilitate the integration of HOC-EC in human machine
      interfaces, such as pervasive healthcare systems, enhancing their affective
      character and providing information about the user's emotional status (e.g.,
      identifying user's emotion experiences, recurring affective states, time
      dependent emotional trends).

PMID- 19858034
TI  - Using heterogeneous wireless sensor networks in a telemonitoring system for
      healthcare.
AB  - Ambient intelligence has acquired great importance in recent years and requires
      the development of new innovative solutions. This paper presents a distributed
      telemonitoring system, aimed at improving healthcare and assistance to dependent
      people at their homes. The system implements a service-oriented architecture
      based platform, which allows heterogeneous wireless sensor networks to
      communicate in a distributed way independent of time and location restrictions.
      This approach provides the system with a higher ability to recover from errors
      and a better flexibility to change their behavior at execution time. Preliminary
      results are presented in this paper.

PMID- 19858035
TI  - Universal glucose models for predicting subcutaneous glucose concentration in
      humans.
AB  - This paper tests the hypothesis that a "universal," data-driven model can be
      developed based on glucose data from one diabetic subject, and subsequently
      applied to predict subcutaneous glucose concentrations of other subjects, even of
      those with different types of diabetes. We employed three separate studies, each
      utilizing a different continuous glucose monitoring (CGM) device, to verify the
      model's universality. Two out of the three studies involved subjects with type 1
      diabetes and the other one with type 2 diabetes. We first filtered the
      subcutaneous glucose concentration data by imposing constraints on their rate of
      change. Then, using the filtered data, we developed data-driven autoregressive
      models of order 30, and used them to make short-term, 30-min-ahead glucose
      concentration predictions. We used same-subject model predictions as a reference
      for comparisons against cross-subject and cross-study model predictions, which
      were evaluated using the root-mean-squared error (RMSE) and Clarke error grid
      analysis (EGA). We found that, for each studied subject, the average cross
      subject and cross-study RMSEs of the predictions were small and indistinguishable
      from those obtained with the same-subject models. These observations were
      corroborated by EGA, where better than 99.0% of the paired sensor-predicted
      glucose concentrations lay in the clinically acceptable zone A. In addition, the
      predictive capability of the models was found not to be affected by diabetes
      type, subject age, CGM device, and interindividual differences. We conclude that
      it is feasible to develop universal glucose models that allow for clinical use of
      predictive algorithms and CGM devices for proactive therapy of diabetic patients.

PMID- 19858036
TI  - Hepatocyte growth factor suppresses transforming growth factor-beta-1 and type
      III collagen in human primary renal fibroblasts.
AB  - Tubulointerstitial changes in the diabetic kidney correlate closely with renal
      fibrosis, and transforming growth factor-beta-1 (TGF-beta1) is thought to play a
      key role in this process. In contrast, hepatocyte growth factor (HGF) has shown
      therapeutic effects on injured renal tubules in animal models. This study was
      undertaken to test the hypothesis that the preventive effects of HGF may result
      from interventions in TGF-beta1-mediated signaling and collagen III secretion. We
      examined the expression of HGF/HGF receptor (c-Met) and TGF-beta1 in renal
      fibroblasts at multiple time points. The effects of recombinant human HGF on TGF
      beta1 expression were studied by RT-PCR and Western blotting, and the levels of
      collagen III were measured by ELISA. In the high-glucose condition, the
      expression of HGF and c-Met in renal fibroblasts was detected as early as 6 hours
      following cell culture while the level of TGF-beta1 peaked at 96 hours. The
      addition of recombinant human HGF to the culture media dose-dependently inhibited
      TGF-beta1 mRNA expression and reduced collagen III secretion by 34%. These
      results indicate that, during hyperglycemia, HGF inhibits TGF-beta1 signaling and
      type III collagen activation in interstitial fibroblasts. Furthermore, we should
      recognize that changes in the balance between HGF and TGF-beta1 might be decisive
      in the pathogenesis of chronic renal fibrosis. Therefore, administration of HGF
      to restore this balance may offer a novel therapeutic intervention in managing
      renal fibrogenesis in diabetic nephropathy.

PMID- 19858037
TI  - Follow-up study of behavioral development and parenting stress profiles in
      children with congenital hypothyroidism.
AB  - Recent longitudinal experiences have emphasized that the follow-up of children
      with treated congenital hypothyroidism (CHT) should not be limited to the
      cognitive domain. This study attempted to evaluate the emotional-behavioral
      profiles in children with CHT together with maternal parenting stress profiles.
      Data for child and family characteristics were collected from 47 families with a
      3-12-year-old CHT child diagnosed and treated since the newborn period. Cognitive
      assessments were performed. The main caregiver completed the following
      questionnaires: (1) Strengths and Difficulties Questionnaire, which rated
      behavioral symptoms in children; (2) Parenting Stress Index, which determined the
      quality and magnitude of parenting stress experienced by the caregiver; and (3)
      Symptom Checklist-90-R, which evaluated the psychopathological symptoms of the
      caregiver. In addition, 31 unaffected siblings were recruited as a comparative
      control group. The results revealed that children with treated CHT had normal
      intelligence quotients (mean, 93.6 +/- 16.2) at the time of the study. However,
      CHT children had more problems in emotional-behavioral domains than sibling
      controls (p = 0.01). Overall, 29.8% (14/47) of the CHT children had emotional
      behavioral problems above the clinical cutoff. In addition, 13% of the caregivers
      of CHT children had parenting stress above the clinical cutoff. Therefore,
      professional intervention is warranted in these subgroups of CHT children and
      parents.

PMID- 19858038
TI  - Intraobserver and interobserver variability of Fuhrman and modified Fuhrman
      grading systems for conventional renal cell carcinoma.
AB  - The Fuhrman nuclear grade is the most widely used grading system for renal cell
      carcinoma. The aim of this study was to evaluate the intraobserver and
      interobserver variability of the Fuhrman and modified Fuhrman grading systems for
      conventional renal cell carcinoma. In this study, five pathologists independently
      classified 110 cases of conventional renal cell carcinoma according to the
      Fuhrman and modified (three- and two-tiered) Fuhrman grading systems. The
      intraobserver and interobserver variability of these systems were assessed using
      kappa statistics. The associations between the Fuhrman and modified Fuhrman
      grades, pathologic stage and tumor size were determined by correlation analysis.
      The intraobserver and interobserver combined mean kappa values for four-tiered
      Fuhrman grading were 0.48 and 0.41, respectively. The highest agreement was
      detected in two-tiered modification (including grades 1 + 2 and 3 + 4); the
      intraobserver and interobserver combined mean kappa values were 0.67 and 0.62,
      respectively. Correlations between pathologic stage and tumor size with two
      tiered modification (including grades 1 + 2 and 3 + 4) were greater than those in
      three- and four-tiered Fuhrman grading. Collapsing the Fuhrman grading into a two
      tiered scheme improved the intraobserver and interobserver reproducibility.

PMID- 19858039
TI  - Simultaneous 99mTc and 123I dual-isotope brain striatal phantom single photon
      emission computed tomography: validation of 99mTc-TRODAT-1 and 123I-IBZM
      simultaneous dopamine system brain imaging.
AB  - [2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]-oct-2-yl]-methyl](2
      mercaptoethyl)-amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2]oxo-[1R-exo
      exo)])-[99mTc]-technetium (99mTc-TRODAT-1) and 123I-iodobenzamide (123I-IBZM) are
      radiotracers for brain dopamine pre- and postsynaptic neuron imaging. The purpose
      of this study was to evaluate imaging parameters and crossed energy interference
      using simultaneous single photon emission computed tomography (SPECT) 99mTc and
      123I data acquisition. A five-compartment brain striatal phantom was filled with
      99mTc and/or 123I radioactive solutions with different striatal-to-background
      ratios, ranging from 3:1 to 9:1. SPECT data were acquired with energy window
      settings of 15% for the centered window at 140 keV for 99mTc and a 10% asymmetric
      window at 159 keV for 123I. The experiments were carried out using either
      individual (99mTc or 123I only) or both radionuclides. The striatal-to-background
      ratios and energy crossed interference between 99mTc and 123I were calculated.
      The phantom SPECT images demonstrated that the energy crossed interferences from
      123I to 99mTc, and vice versa, were 22 +/- 12.4% and 0.4 +/- 1.0%, respectively.
      A net interference of 7.1 +/- 4.0% for the counts in the 15% centered 99mTc
      window can be expected from 123I and a net interference of 1.6 +/- 3.3% for the
      counts in the 10% asymmetric 123I window was derived from 99mTc. The correlation
      of striatal-to-background ratios between single isotope and simultaneous dual
      isotope was excellent (R2 = 0.99). The imaging parameters used in this
      simultaneous dualisotope SPECT imaging could be used in future clinical practice
      for imaging patients with movement disorders by using 99mTc-TRODAT-1 and 123I
      IBZM. The striatal-to-background ratios were not affected by the crossed
      interference between 99mTc and 123I.

PMID- 19858040
TI  - Diagnosis and treatment of comorbidities of Tourette's syndrome and bipolar
      disorder in a 10-year-old boy.
AB  - Changes in moods are one of the comorbid psychiatric manifestations that
      frequently occur in patients with Tourette's syndrome. The assessment of a manic
      episode in children with Tourette's syndrome is challenging. Furthermore, the
      treatment of children with comorbid mania and Tourette's syndrome has not been
      extensively studied. We present a 10-year-old boy who suffered from both
      Tourette's syndrome and mania, whose symptoms improved after using lithium and
      risperidone. The child was diagnosed with Tourette's syndrome at 7 years of age
      when he suffered from tics and experienced his first manic episode. He received
      monotherapy, including haloperidol, risperidone and aripiprazole, and the
      response was poor. When the combination of lithium and risperidone was used, the
      tics and mania subsided. It is important to assess individuals with Tourette's
      syndrome for associated bipolar disorder. The treatment of children with both
      disorders is a major clinical issue, and our case may serve as an example for
      successful treatment strategies.

PMID- 19858041
TI  - Female epispadias: a case report and review of the literature.
AB  - Isolated female epispadias without exstrophy is an extremely rare syndrome. The
      symptoms of female epispadias are primary urinary incontinence and abnormal
      anatomical features. A 12-year-old girl presented with primary urinary
      incontinence. On physical examination, bifid clitoris and labia minora were seen.
      The vagina and hymen were normal. Voiding cystourethrogram showed no reflux. With
      the diagnosis of isolated female epispadias, one-stage reconstruction of the
      urethra, bladder neck and labia minora and clitoris was performed.

PMID- 19858042
TI  - Intravitreal ranibizumab for the treatment of choroidal neovascularization
      secondary to endogenous endophthalmitis.
AB  - Choroidal neovascularization is a major cause of visual loss in age-related
      macular degeneration. It is also a potential vision-threatening complication of
      pathologic myopia, uveitis, traumatic choroidal rupture and, rarely,
      endophthalmitis. Here, we report a 36-year-old woman with acute lymphocytic
      leukemia and fungal pneumonia after chemotherapy who developed endogenous
      endophthalmitis in both eyes. The infection was controlled by systemic antibiotic
      and antifungal agents. Unfortunately, choroidal neovascularization developed in
      the right macula 1 month later. One dose of intravitreal injection of ranibizumab
      (0.5 mg/0.05 mL) was given, and the macular exudates resolved rapidly. There was
      no recurrence or complications during the 10-month follow-up.

PMID- 19858043
TI  - Silver-containing hydrofiber dressing is an effective adjunct in the treatment of
      pemphigus vulgaris.
AB  - Pemphigus vulgaris is a life-threatening autoimmune bullous dermatosis and its
      management represents a major challenge to medical teams. The primary treatments
      for pemphigus vulgaris are oral steroids and immunosuppressants, but topical
      approaches also play a role in disease management. Here, we report a patient with
      pemphigus vulgaris involving 62% of the total body surface area, with initial
      poor clinical response to systemic steroids and topical silver sulfadiazine
      therapy. However, a marked improvement in wound healing and decreased patient
      discomfort were observed after application of silver-containing hydrofiber
      dressings (Aquacel-Ag). Therefore, silver-containing hydrofiber dressings may
      offer an effective adjunct in the treatment of patients with pemphigus vulgaris
      with extensive skin involvement. Our encouraging experience with these dressing
      patches may be extended to manage other large exudation wounds.

PMID- 19858044
TI  - [Radiofrequency ablation in the treatment of liver and lung tumors].
AB  - Radiofrequency (RF) ablation is a technique of thermotherapy which emerged over
      the last fifteen years in the field of oncology. RF directed toward a specific
      tumor mass is known to be very effective (over 90%) for treating tumors less than
      2.5 cm. RF is used for patients with early-stage lung or liver cancers who are
      not surgical candidates, With improvements in systemic therapy, increasing
      interest in the use of local therapy for metastases has arisen. Eradication of
      residual metastases via local therapies has a sense in patients with stabilized
      disease. Nonsurgical alternative like RF has become popular because it is less
      invasive than surgery and has demonstrated great efficiency. Nevertheless
      prospective randomized trials to compare RF with surgery are difficult to
      achieve, prospective studies are needed to better evaluate the technique.

PMID- 19858045
TI  - [CT and MRI imaging in tumoral angiogenesis].
AB  - Angiogenesis is the process of activating dormant endothelial cells to form new
      vessels, after stimulation and it is essential in tumor growth. In many types of
      cancer, angiogenesis results from the activation of oncogenes that stimulate the
      production of Vascular Endothelial Growth Factor (VEGF). However, these newly
      formed vessels have a great number of abnormalities: increased density of fragile
      and hyper-permeable microvessels, arterial-venous shunts, caliber abnormalities
      and flow instabilities susceptible to flow direction inversion according to
      interstitial pressure. Anti-angiogenic treatments inhibit VEGF activity,
      perceived as structural and functional normalization of the microvascular
      pattern, such as reduced density of microvessels and restored morphology of the
      remaining ones. Conventional imaging techniques are not sensible to these
      changes, at best they show tumor size stabilization, hence the need of new
      techniques. Microvascularization imaging can be achieved by detecting functional
      disturbances to blood flow and not by showing the microvasculature per se. These
      techniques are based in quantifying the enhancement in tumor due to the passage
      of contrast agent after injection or protons labeled by a magnetic field. Through
      these measurements, one can derive interstitial and blood volumes as well as the
      tissue perfusion and capillary wall permeability. Microvascular imaging has
      greatly benefited from the improvements seen in CT and MRI equipment allowing
      large volume coverage with high spatial and temporal resolutions as from the
      evolutions in the methods to calculate, present and compare maps of the
      microcirculation and it's heterogeneity. However, software to analyze
      microvascularization are still rare, limiting the technique's application and
      validation in large scale. Nevertheless, imaging of the microcirculation is
      useful throughout the care of the oncological patient: it can reinforce the
      suspicious nature of a lesion, suggest anti-angiogenic treatment efficacy in
      hypervascular lesions, and show early treatment response before morphological
      changes as in RECIST criteria.

PMID- 19858046
TI  - [Interventional radiology procedures in the treatment of bone metastasis].
AB  - Over the last ten years, there has been much development in the treatment of bone
      metastases using percutaneous image-guided interventional radiology procedures.
      They are helpful in the management of patients resulting in stabilization of bone
      lysis in order to achieve additional biomechanical stability and in significant
      symptomatic relief. Vertebroplasty consisting in an injection of an acrylic
      cement into a structurally weakened or destructed bone plays a major role in the
      management of specific bone weakening. Advances have been made also with the
      application of thermoablation procedures to bone tumors (radiofrequency ablation,
      cryotherapy). Since conservative treatment with analgesics is often insufficient
      and the analgesic effect of radiation therapy is delayed and sometimes
      ineffective, these image-guided procedures play a beneficial role in the
      management of bone metastases and need more evaluation.

PMID- 19858047
TI  - Impact on drug cost and use of   Medicare part D of medication   therapy
      management services   delivered in 2007.
AB  - OBJECTIVE: To describe experiences with medication therapy management (MTM)
      services delivered to benefciaries of Mirixa's health plan clients. SETTING:
      United States during 2007. PRACTICE DESCRIPTION: Three intervention modalities
      were offered to provide MTM services: community pharmacy, pharmacist-staffed call
      centers, and educational mailings. Available data were analyzed to identify any
      differences among patients receiving any of the three interventions. Patients
      included in the analysis were those who qualifed for MTM services between April
      1, 2007, and June 30, 2007. MTM services were provided for these patients between
      May 1, 2007, and December 31, 2007. PRACTICE INNOVATION: The MirixaPro platform
      was created to document the activities associated with the five core elements of
      an MTM service (medication therapy review, creation of a personal medication
      record, creation of a medication-related action plan [MAP], intervention and/or
      referral, and documentation and follow-up). It provides a framework for capturing
      safety interventions, follow-ups with prescribers, and pharmacist instructions to
      the patients. MAIN OUTCOME MEASURES: Part D drug costs, use, and generic
      dispensing ratio in the pre- and post-MTM periods. RESULTS: 21,336 patients
      received MTM services from a community pharmacist (face to face, 9,140; by phone,
      12,196), 3,436 patients received MTM services from a call center pharmacist, and
      49,021 patients received an educational mailing. Patients who had a face-to-face
      session had a decline in mean monthly drug costs of $29 (from $658 to $629),
      while drug costs decreased by $40 (from $677 to $637) when the community
      pharmacist provided the services over the telephone. Mean monthly drug costs
      decreased by $15 (from $676 to $661) for patients receiving MTM services from a
      call center pharmacist and did not change for patients receiving an educational
      mailing ($698 in both periods). CONCLUSION: Among patients who received MTM
      services in 2007, drug costs decreased for those who received service from
      community pharmacists, decreased somewhat for patients who received service from
      a call center pharmacist, and were unchanged for those who received MTM via
      mailing. Further studies are needed to assess the effect of various types of MTM
      interventions on fnancial, clinical, and humanistic outcomes.

PMID- 19858048
TI  - Multiple bony amyloidomas as an initial presentation of myeloma.
AB  - Amyloidosis complicating multiple myeloma is an uncommon but well-recognized
      phenomenon. Multiple bone amyloidomas are rare as the initial presenting feature
      of myeloma. Solitary bone amyloidomas share common features with those of
      patients who have solitary plasmacytomas and progression to disseminated myeloma
      is common. We report a case of an elderly man who presented with extensive
      amyloid deposition in multiple plasmacytoma sites as well as evidence of amyloid
      in a fat pad aspirate but with none of the usual organ damage associated with
      systemic amyloidosis. This presentation is similar to a subset of patients said
      to have macrofocal myeloma. These patients are typically aged < 40 years, have no
      bone marrow involvement, and have a good prognosis. This report may represent the
      first description of macrofocal myeloma associated with amyloid deposition in an
      older individual.

PMID- 19858049
TI  - Low-dose gemcitabine efficacious in three patients with tumor-stage mycosis
      fungoides.
AB  - Mycosis fungoides is the most common subtype of mature T-cell lymphoma that
      primarily arises in the skin. The tumor manifests as patches, plaques, tumors, or
      erythroderma and can secondarily involve lymph nodes, peripheral blood, and
      visceral organs. In advanced tumor stage, chemotherapy is a second-line approach,
      which is generally not considered curative. Initially, most patients profit from
      this treatment, but observed remissions usually do not exceed several months.
      Because of possible immunosuppressive effects in vulnerable patients, the overall
      benefit of chemotherapy itself is not unequivocal in cutaneous T-cell lymphoma.
      We report 3 patients whose tumor-stage mycosis fungoides was not sufficiently
      controlled by several preceding systemic therapies, including liposome
      encapsulated doxorubicin. All patients experienced excellent improvement with 250
      mg/m2 gemcitabine weekly, a low-dose regimen that is predicted to be less toxic
      compared with standard-dose gemcitabine.

PMID- 19858050
TI  - Emergence of chronic myelogenous leukemia from a background of myeloproliferative
      disorder: JAK2V617F as a potential risk factor for BCR-ABL translocation.
AB  - We report the emergence of chronic myelogenous leukemia (CML) in a patient with
      JAK2V617F-positive polycythemia vera after 15 years of phlebotomy. The
      polycythemia vera clinical and molecular findings were suppressed at the time of
      CML diagnosis, only to re-emerge after the leukemia was successfully treated with
      imatinib. We explored the potential association between myeloproliferative
      disorders and CML in the context of the current literature and found a higher
      than-expected coincidence based on known epidemiologic data for each specific
      condition. We hypothesize that myeloproliferative disorder (JAK2V617F or
      molecular events that cause JAK2V617F) is a risk factor for CML (BCR-ABL
      translocation). Because of therapeutic implications, clinicians should be aware
      that the conditions co-occur more frequently than once thought.

PMID- 19858052
TI  - Clinical Lymphoma & Myeloma . . . and leukemia too!

PMID- 19858054
TI  - Management of immunocompetent patients with primary central nervous system
      lymphoma.
AB  - Primary central nervous system (CNS) lymphoma (PCNSL) is a non-Hodgkin lymphoma
      that arises within and is confined to the CNS. Recent data have suggested an
      increasing incidence in immunocompetent individuals, with a peak of incidence
      between 60 and 70 years of age. Patients with PCNSL present mostly with symptoms
      of increased intracranial pressure. The clinical management of these patients
      remains controversial, and the optimal treatment for patients with PCNSL has not
      yet been defined. Surgery, even if macroscopically radical, does not improve
      survival because of the multifocal and infiltrative nature of PCNSL; furthermore,
      the deep location of most of these tumors makes patients susceptible to serious
      and irreversible neurologic sequelae. Corticosteroids have a specific role in the
      treatment of patients with PCNSL, whose disease is sensitive to them as a
      chemotherapeutic agent. PCNSL is an extremely radiation-sensitive neoplasm; whole
      brain radiation therapy plus corticosteroids was the first modality of treatment
      for patients with this neoplasm until 10 years ago, with a low cure rate and a
      high local recurrence rate. PCNSL is also a chemosensitive neoplasm; while the
      optimal choice, sequence, and combination of appropriate agents for efficacious
      treatment of patients with PCNSL has yet to be determined. An essential component
      of therapy must include an adequate drug delivery behind a normal blood-brain
      barrier. Methotrexate is the agent with the most proven activity in PCNSL.
      Combined-modality therapy has improved survival, but relapse is still common, and
      late neurologic toxicity is a significant complication, especially in older
      patients, who represent the majority of immunocompetent patients with PCNSL.

PMID- 19858055
TI  - Infectious complications in patients with chronic lymphocytic leukemia:
      pathogenesis, spectrum of infection, and approaches to prophylaxis.
AB  - Infections continue to be a major cause of morbidity and mortality in patients
      with chronic lymphocytic leukemia (CLL), as therapeutic advances have occurred
      over the past several decades. The pathogenesis of infection in these patients is
      multifactorial, including inherent immune defects related to the primary disease
      process, such as hypogammaglobulinemia, as well as therapy-related
      immunosuppression. A characteristic spectrum of infectious complications has been
      described for specific treatment agents. With chlorambucil, most infections are
      bacterial in origin, caused by common Gram-positive and -negative organisms.
      Recurrent infections are a hallmark, with the respiratory tract being the most
      common site of infection. The pathogenesis of infection with the purine analogues
      is related to the quantitative and qualitative T-cell abnormalities induced by
      these agents. Risk factors for infection identified in patients treated with
      fludarabine include advanced-stage disease, prior CLL therapy, response to
      therapy, elevated serum creatinine, hemoglobin < 12 g/dL, and decreased serum
      IgG. As compared with patients receiving chlorambucil, patients receiving
      fludarabine have more major infections and herpes virus infections. However,
      Pneumocystis, Aspergillus, and cytomegalovirus (CMV) infections are uncommon. The
      use of alemtuzumab is complicated by frequent opportunistic infections. CMV
      reactivation is especially problematic, occurring in 10%-25% of patients. For
      prevention of infection, the use of vaccinations and immunoglobulin replacement
      has been studied. Recommendations for prophylactic antimicrobial therapy have
      arisen from CLL treatment trials and anecdotal reports. As new treatment
      approaches are developed for CLL, one must consider not only the efficacy of
      these agents for disease response but also the effect on subsequent infectious
      complications. Infectious complications remain a significant cause of morbidity
      and mortality in patients with CLL. We will review the pathogenesis as well as
      the spectrum of infections in these patients. We will also discuss approaches to
      the prophylactic and therapeutic management of infections in these patients.

PMID- 19858056
TI  - Microsatellite instability is a common finding in multiple myeloma.
AB  - PURPOSE: Microsatellite instability (MSI) occurs as a result of sliding in the
      DNA sequences from shortening or elongation of the repeat zones of DNA during
      replication. Such abnormalities can normally be corrected by the enzymes coded by
      the DNA mismatch repair (MMR) genes. Therefore, detection of MSI is considered to
      be a sign of disorder of the MMR genes and is interpreted as a replication error
      phenotype. PATIENTS AND METHODS: We evaluated the MSI in 5 different loci in the
      14q32 region of immunoglobulin heavy chain IgH gene in 26 newly diagnosed
      patients with multiple myeloma (MM). RESULTS: Fifty-four percent of the patients
      disclosed MSI and at least 1 locus but no significant association of MSI was
      found between different clinical stages and the MM subtype. MSI was not found in
      5 light-chain myeloma patients. CONCLUSION: Although our case number is small,
      probably the genomic instability in heavy-chain MM may be a common finding and
      probably plays a critical role in the MM pathogenesis.

PMID- 19858057
TI  - Kyphoplasty for patients with multiple myeloma is a safe surgical procedure:
      results from a large patient cohort.
AB  - INTRODUCTION: Only in recent years has balloon kyphoplasty gained significance in
      the treatment of vertebral fractures as an adequate minimally invasive vertebral
      stabilization technique. Kyphoplasty has also increasingly been used to treat
      vertebral osteolyses caused by multiple myeloma (MM). PATIENTS AND METHODS: In
      our cohort of 76 patients with MM with a total of 190 vertebral fractures treated
      with kyphoplasty, we performed a 30-day postoperative analysis of cement leakage,
      neurologic symptoms, pulmonary embolism, and infections. RESULTS: Painful
      osteolytic or fractured vertebrae or even imminent vertebral instability caused
      by osteolyses were seen as indications for kyphoplasty. One case of pulmonary
      embolism was observed because of cement leakage as the only postoperative
      complication. CONCLUSION: By careful interdisciplinary indication setting and a
      standardized treatment model, kyphoplasty presents a very safe and effective
      procedure for the treatment of vertebral osteolyses and fractures caused by MM.

PMID- 19858058
TI  - Rituximab combined with MACOP-B or VACOP-B and radiation therapy in primary
      mediastinal large B-cell lymphoma: a retrospective study.
AB  - BACKGROUND: Third-generation regimens (MACOP-B [methotrexate/leucovorin
      (LV)/doxorubicin/cyclophosphamide/vincristine/ prednisone/bleomycin] or VACOP-B
      [etoposide/LV/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin]) in
      combination with local radiation therapy seem to improve lymphoma-free survival
      of primary mediastinal large B-cell lymphoma (PMLBCL). Recently, the superiority
      of R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/ prednisone)
      over CHOP-like regimens has been demonstrated in elderly and younger patients
      with low-risk diffuse large B-cell lymphoma. PATIENTS AND METHODS:
      Retrospectively, between February 2002 and July 2006, 45 previously untreated
      patients with PMLBCL were treated with a combination of a third-generation
      chemotherapy regimen (MACOP-B or VACOP-B), concurrent rituximab, and mediastinal
      radiation therapy. RESULTS: Twenty-six (62%) patients achieved a complete
      response (CR), and 15 (36%) obtained a partial response after MACOP-B/VACOP-B
      plus rituximab. After radiation therapy, the CR rate was 80%. At a median follow
      up of 28 months, among the 34 patients who obtained a CR, 3 relapsed after 16,
      19, and 22 months, respectively. Projected overall survival was 80% at 5 years;
      the relapse-free survival (RFS) curve of the 34 patients who achieved CR was 88%
      at 5 years. CONCLUSION: In this retrospective study, in patients with PMLBCL,
      combined-modality treatment using the MACOP-B/VACOP-B regimen plus rituximab
      induces a high remission rate, with patients having a > 80% chance of surviving
      relapse free at 5 years. In comparison with historical data on MACOP-B/VACOP-B
      without rituximab, there are no statistically significant differences in terms of
      CR and RFS rates.

PMID- 19858059
TI  - Rituximab and dose-dense chemotherapy in primary testicular lymphoma.
AB  - BACKGROUND: Treatment of primary testicular lymphoma (PTL) remains unsatisfactory
      even in patients with good prognosis, as < 30% of patients are alive at 3 years.
      PATIENTS AND METHODS: We began a phase II study to assess efficacy and toxicity
      of a dose-dense cyclophosphamide/epirubicin/vincristine/prednisone (CEOP14)
      regimen with rituximab (CEOP14R) in 38 previously untreated patients with PTL
      with early-stage (I or II) and low-risk disease, followed by adjuvant radiation
      therapy and central nervous system prophylaxis. RESULTS: Complete response was
      86% (similar to historical controls), but improvement in outcome was observed;
      with actuarial curves at 5 years, event-free survival was 70%, and overall
      survival was 66%. Toxicity was mild, and the regimen was well tolerated.
      CONCLUSION: The addition of rituximab to dose-dense chemotherapy improves outcome
      in this setting of patients who previously had been considered to have the
      poorest prognosis. It is important that these findings will be validated in
      multicentric, controlled clinical trials.

PMID- 19858060
TI  - IGHV unmutated status influences outcome more than IGHV1-69 gene usage per se in
      patients with chronic lymphocytic leukemia.
AB  - In this study, IGHV1-69 gene usage was detected in 46 out of 379 cases (12%) of
      chronic lymphocytic leukemia (CLL). In comparison with patients using alternative
      immunoglobulin heavy-chain variable (IGHV) genes, patients with IgHV1-69 CLLs
      more often presented at advanced stage, lacked somatic hypermutation (unmutated
      cases, 87% vs. 35%; P = .00001), and expressed unfavorable biologic
      characteristics. In 12 patients (26%), common amino acid motifs within the heavy
      chain third complementarity-determining region were identified, allowing
      assignment to previously reported stereotyped subsets. In our study, treatment
      free survival of patients with unmutated IGVH1-69 did not differ significantly
      from that of patients expressing unmutated alternative IGHV genes. As such, IGHV1
      69 gene usage per se did not seem to be predictive of progressive disease,
      progression being primarily related to the unmutated IGHV profile.

PMID- 19858061
TI  - Bortezomib and dexamethasone therapy for newly diagnosed patients with multiple
      myeloma complicated by renal impairment.
AB  - BACKGROUND: Renal impairment is a common complication of multiple myeloma (MM)
      and is related to shorter overall survival and increased rates of early death.
      Bortezomib is a new agent for the treatment of patients with myeloma, with high
      response rates and controllable side effects. In this study, we will evaluate the
      efficacy and safety of bortezomib and dexamethasone in patients with newly
      diagnosed MM complicated by renal impairment. PATIENTS AND METHODS: This is a
      prospective study of the general characteristics, reversibility of renal
      impairment, response of myeloma, and side effects of 18 consecutive newly
      diagnosed patients with MM and renal impairment who received > or = 2 cycles of
      bortezomib and dexamethasone. RESULTS: Of 18 patients newly diagnosed with MM,
      the median age was 60 years, and the median serum creatinine was 5.3 mg/dL.
      Patients received a median of 4 cycles of bortezomib and dexamethasone. Reversal
      of renal impairment was documented in 38.9% of the patients, and the median time
      to reversal was 16 days. Moreover, 33.3% of the patients achieved renal response
      (a 50% decrease in serum creatinine). The overall response rate of MM was 83.3%,
      including a 33.3% complete response (CR) rate, a 16.7% near-CR rate, a 16.7% very
      good partial response (PR) rate, and a 16.7% PR rate. Grade 3/4 adverse events
      consisted of infection (n = 3), peripheral neuropathy (n = 3), and ileus (n = 1).
      After a median follow-up of 15.7 months, the median progression-free survival for
      all patients was 12.6 months. CONCLUSION: Bortezomib plus dexamethasone is a safe
      and effective regimen for newly diagnosed patients with MM complicated by renal
      impairment.

PMID- 19858063
TI  - Statement by an American Association of Clinical Endocrinologists/American
      College of Endocrinology consensus panel on type 2 diabetes mellitus: an
      algorithm for glycemic control.
AB  - This report presents an algorithm to assist primary care physicians,
      endocrinologists, and others in the management of adult, nonpregnant patients
      with type 2 diabetes mellitus. In order to minimize the risk of diabetes-related
      complications, the goal of therapy is to achieve a hemoglobin A1c (A1C) of 6.5%
      or less, with recognition of the need for individualization to minimize the risks
      of hypoglycemia. We provide therapeutic pathways stratified on the basis of
      current levels of A1C, whether the patient is receiving treatment or is drug
      naive. We consider monotherapy, dual therapy, and triple therapy, including 8
      major classes of medications (biguanides, dipeptidyl-peptidase-4 inhibitors,
      incretin mimetics, thiazolidinediones, alpha-glucosidase inhibitors,
      sulfonylureas, meglitinides, and bile acid sequestrants) and insulin therapy
      (basal, premixed, and multiple daily injections), with or without orally
      administered medications. We prioritize choices of medications according to
      safety, risk of hypoglycemia, efficacy, simplicity, anticipated degree of patient
      adherence, and cost of medications. We recommend only combinations of medications
      approved by the US Food and Drug Administration that provide complementary
      mechanisms of action. It is essential to monitor therapy with A1C and self
      monitoring of blood glucose and to adjust or advance therapy frequently (every 2
      to 3 months) if the appropriate goal for each patient has not been achieved. We
      provide a flow-chart and table summarizing the major considerations. This
      algorithm represents a consensus of 14 highly experienced clinicians, clinical
      researchers, practitioners, and academicians and is based on the American
      Association of Clinical Endocrinologists/American College of Endocrinology
      Diabetes Guidelines and the recent medical literature.

PMID- 19858064
TI  - American Association of Clinical Endocrinologists medical guidelines for clinical
      practice for growth hormone use in growth hormone-deficient adults and transition
      patients - 2009 update: executive summary of recommendations.

PMID- 19858065
TI  - Increased use of proton pump inhibitors in patients with diabetes and neuropathy.

PMID- 19858066
TI  - Effects of pioglitazone, a peroxisome proliferator-activated receptor gamma
      agonist, on the urine and urothelium of the rat.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors, which belong to the nuclear receptor superfamily. Some
      PPARgamma agonists, such as pioglitazone, and dual PPARgamma/PPARalpha agonists,
      such as muraglitazar, induced urothelial bladder tumors in rats but not in mice.
      In this study, we investigated the early effects in the urine and bladder of rats
      treated with pioglitazone to evaluate the possible relation between urinary
      solids formation and urothelial cytotoxicity and regenerative proliferation. In a
      4-week experiment, treatment of rats with 16 mg/kg pioglitazone induced
      cytotoxicity and necrosis of the urothelial superficial layer, with increased
      cell proliferation measured by bromodeoxyuridine labeling index and hyperplasia
      by histology. It also produced alterations in urinary solid formation, especially
      calcium-containing crystals and calculi. PPARgamma agonists (pioglitazone and
      troglitazone) in vitro reduced rat urothelial cell proliferation and induced
      uroplakin synthesis, a specific differentiation marker in urothelial cells. Our
      data support the hypothesis that the bladder tumors produced in rats by
      pioglitazone are related to the formation of urinary solids. This strongly
      supports the previous conclusion in studies with muraglitazar that this is a rat
      specific phenomenon and does not pose a urinary bladder cancer risk to humans
      treated with these agents.

PMID- 19858067
TI  - Effects of cytochrome P450 inhibitors on the biotransformation of fluorogenic
      substrates by adult male rat liver microsomes and cDNA-expressed rat cytochrome
      P450 isoforms.
AB  - We have evaluated the use of a panel of six fluorogenic cytochrome P450 (CYP)
      substrates as a potential tool for rapid screening for global changes in CYP
      activity in rats under different physiological conditions. The biotransformation
      of 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC), 7
      benzyloxy-4-(trifluoromethyl)-coumarin, 7-benzyloxyquinoline, 3-cyano-7
      ethoxycoumarin, 7-methoxy-4-(trifluoromethyl)-coumarin, and 7-ethoxy-4
      trifluoromethyl-coumarin by microsomes from adult male rat liver were
      characterized, their sensitivities to 15 putative inhibitors were determined and
      compared to similar experiments using nine different complementary DNA (cDNA)
      expressed rat CYPs. Inhibitory profiles of the substrates in microsomes were
      different from each other, with some overlap, suggesting that each substrate is
      to some extent biotransformed by a different CYP isoform. Ketoconazole and
      clotrimazole were nonselective inhibitors, while ticlopidine selectively
      inhibited biotransformation of AMMC. CYP2A1 did not biotransform any of the
      substrates, and CYP2E1 was insensitive to all the inhibitors tested. Some
      inhibitors did not affect the biotransformation of the fluorogenic substrates by
      cDNA-expressed isoforms as predicted by their effects on conventional substrates,
      e.g., chlorzoxazone and diethyldithiocarbamate were inactive against CYP2E1, and
      CYP2C6 was not inhibited by sulfaphenazole. When results in microsomes and cDNA
      expressed CYPs were compared, only the majority of the biotransformation of AMMC
      by microsomes could be assigned with full confidence to a specific CYP isoform,
      namely CYP2D2. Nevertheless, different inhibitory profiles of the substrates
      indicate that the panel will be useful for rapid functional quantification of
      global CYP activity in rats under different experimental conditions. Our results
      also demonstrate the inappropriateness of extrapolating inhibitory data between
      conventional and fluorogenic CYP substrates.

PMID- 19858068
TI  - Vertebrate rhodopsin adaptation to dim light via rapid meta-II intermediate
      formation.
AB  - Rhodopsin is a photoreceptive protein present in vertebrate rod photoreceptor
      cells, which are responsible for scotopic vision. Recent molecular studies have
      shown that several aquatic vertebrate species have independently acquired
      rhodopsin containing Asp83Asn, Glu122Gln, and Ala292Ser substitutions, causing a
      blue shift in the rhodopsin absorption spectra for adaptation to the blue-green
      photic environment in deep water. Here, we provide new evidence for the
      evolutionary and functional relevance of the Asp83Asn substitution. Spectroscopic
      and kinetic analyses of rhodopsins in six cichlid fishes from the East African
      Great Lakes using charge-coupled device spectrophotometer revealed that the
      Asp83Asn substitution accelerated the formation of meta-II, a rhodopsin
      intermediate crucial for activation of the G-protein transducin. Because rapid
      formation of meta-II likely results in effective transduction of photic signals,
      it is reasonable to assume that deep-water cichlid species have acquired
      rhodopsin containing Asn83 to adapt to dim lighting. Remarkably, rhodopsin
      containing Asn83 has been identified in terrestrial vertebrates such as bats, and
      these rhodopsin variants also exhibit accelerated meta-II formation. Our results
      indicated that the Asp83Asn substitution observed in a variety of animal species
      was acquired independently in many different lineages during vertebrate evolution
      for adaptation to dimly lit environments.

PMID- 19858069
TI  - Cancer stem cells: a reality, a myth, a fuzzy concept or a misnomer? An analysis.
AB  - The concept of cancer stem cells (CSC) embodies two aspects: the stem cell as the
      initial target of the oncogenic process and the existence of two populations of
      cells in cancers: the CSC and derived cells. The second is discussed in this
      review. CSC are defined as cells having three properties: a selectively endowed
      tumorigenic capacity, an ability to recreate the full repertoire of cancer cells
      of the parent tumor and the expression of a distinctive repertoire of surface
      biomarkers. In operational terms, the CSC are among all cancer cells those able
      to initiate a xenotransplant. Other explicit or implicit assumptions exist,
      including the concept of CSC as a single unique infrequent population of cells.
      To avoid such assumptions, we propose to use the operational term tumor
      propagating cells (TPC); indeed, the cells that initiate transplants did not
      initiate the cancer. The experimental evidence supporting the explicit definition
      is analyzed. Cancers indeed contain a fraction of cells mainly responsible for
      the tumor development. However, there is evidence that these cells do not
      represent one homogenous population. Moreover, there is no evidence that the
      derived cells result from an asymmetric, qualitative and irreversible process. A
      more general model is proposed of which the CSC model could be one extreme case.
      We propose that the TPC are multiple evolutionary selected cancer cells with the
      most competitive properties [maintained by (epi-)genetic mechanisms], at least
      partially reversible, quantitative rather than qualitative and resulting from a
      stochastic rather than deterministic process.

PMID- 19858070
TI  - Basic properties and molecular mechanisms of exogenous chemical carcinogens.
AB  - Exogenous chemical carcinogenesis is an extremely complex multifactorial process
      during which gene-environment interactions involving chronic exposure to
      exogenous chemical carcinogens (ECCs) and polymorphisms of cancer susceptibility
      genes add further complexity. We describe the properties and molecular mechanisms
      of ECCs that contribute to induce and generate cancer. A basic and specific
      property of many lipophilic organic ECCs including polycyclic aromatic
      hydrocarbons and polyhalogenated aromatic hydrocarbons is their ability to
      bioaccumulate in the adipose tissue from where they may be released in the blood
      circulation and target peripheral tissues for carcinogenesis. Many organic ECCs
      are procarcinogens and consequently need to be activated by the cytochrome P450
      (CYP) system and/or other enzymes before they can adduct DNA and proteins.
      Because they contribute not only to the cocarcinogenic and promoting effects of
      many aromatic pollutants but also to their mutagenic effects, the aryl
      hydrocarbon receptor-activating and the inducible CYP systems are central to
      exogenous chemical carcinogenesis. Another basic property of ECCs is their
      ability to induce stable and bulky DNA adducts that cannot be simply repaired by
      the different repair systems. In addition, following ECC exposure, mutagenesis
      may also be caused indirectly by free-radical production and by epigenetic
      alterations. As a result of complex molecular interplays, direct and/or indirect
      mutagenesis may especially account for the carcinogenic effects of many exogenous
      metals and metalloids. Because of these molecular properties and action
      mechanisms, we conclude that ECCs could be major contributors to human cancer,
      with obviously great public health consequences.

PMID- 19858071
TI  - Common genetic variation in IGF1, IGFBP1 and IGFBP3 and ovarian cancer risk.
AB  - Insulin-like growth factor (IGF) 1 and its binding proteins foster cellular
      proliferation and inhibit apoptosis. In vitro studies show that IGF1 increases
      ovarian cell growth and invasive potential, suggesting a role for the IGF1
      pathway in ovarian cancer etiology. We evaluated genetic variation in the IGF1,
      IGFBP1 and IGFBP3 genes in relation to ovarian cancer risk by genotyping 29
      haplotype-tagging single nucleotide polymorphisms in 1173 cases and 1201 controls
      from the New England Case-Control (NECC) study and 296 cases and 854 controls
      from the Nurses' Health Study (NHS). The association of haplotypes and single
      nucleotide polymorphisms (SNPs) with ovarian cancer was estimated using
      unconditional (NECC) and conditional (NHS) logistic regression. Additionally, we
      evaluated the association of SNPs with IGF1, IGF-binding protein (IGFBP) 3 and
      IGFBP2 plasma levels (n = 380 NHS controls). Our data suggest a decreased risk
      for women carrying haplotype 2C of the IGF1 gene [odds ratios (ORs) = 0.82, 95%
      confidence intervals (CIs) = 0.69-0.98] and an increased risk for women carrying
      haplotype 1D (OR = 1.41, 95% CI = 1.03-1.94) or 2D (OR = 1.20, 95% CI = 1.01
      1.41) in the binding proteins. When evaluated individually, three SNPs in the
      IGFBPs (rs10228265, rs4988515 and rs2270628) were associated with increased
      ovarian cancer risk, and several IGF1 (rs11111285, rs1996656 and rs1019731) and
      IGFBP3 (rs2270628, rs2854746 and rs2854744) SNPs were significantly associated
      with IGF1, IGFBP3 and IGFBP2 plasma levels. Some haplotypes and SNPs in the IGF
      pathway genes may be associated with ovarian cancer risk; however, these results
      need to be confirmed. Of particular interest was the IGFBP3 SNP rs2270628, which
      was associated with both increased IGF1 plasma levels and higher ovarian cancer
      risk.

PMID- 19858072
TI  - The study of allergy by Japanese researchers: a historical perspective.
AB  - It has been over a hundred years since Shibasaburo Kitasato and Emil Adolf von
      Boehring's finding of a serum component that neutralizes bacterial toxins and the
      subsequent development of antiserum therapy. Over that time, many Japanese
      researchers have greatly contributed to our understanding of the molecular
      mechanisms for allergic and inflammatory diseases. This article is aimed at
      introducing such individual work and how these areas have contributed to our
      understanding of the mechanisms of allergic reactions.

PMID- 19858073
TI  - The specialized iNKT cell system recognizes glycolipid antigens and bridges the
      innate and acquired immune systems with potential applications for cancer
      therapy.
AB  - Invariant NKT (iNKT) cells bridge innate and acquired immunity and play an
      important role in both protective and regulatory responses. The nature of the
      response is dictated by the initial cytokine environment: interaction with IL-10
      producing cells induces negative regulatory T(h)2/regulatory T cell-type iNKT
      cells, while that with IL-12-producing cells results in pro-inflammatory T(h)1
      type responses. Particularly, in the anti-tumor response, iNKT cells mediate
      adjuvant activity by their production of IFN-gamma, which in turn activates both
      innate and acquired immune systems. Thus, upon activation of iNKT cells, both
      MHC(-) and MHC(+) tumor cells can be efficiently eliminated. On the basis of
      these mechanisms, iNKT cell-targeted adjuvant cell therapies have been developed
      and have shown great promise in initial clinical trials on cancer patients.

PMID- 19858075
TI  - Microleakage between composite-wire and composite-enamel interfaces of flexible
      spiral wire retainers. Part 2: comparison of amorphous calcium phosphate
      containing adhesive with conventional lingual retainer composite.
AB  - The aim of this study was to test the hypothesis that there is no difference in
      the microleakage values of a newly developed amorphous calcium phosphate (ACP)
      containing adhesive and a conventional lingual retainer composite at the
      composite-enamel and composite-wire interfaces of flexible spiral wire retainers
      (FSWRs). Sixty freshly extracted human mandibular incisors separated into three
      equal groups were used in this study. Multi-stranded 0.0215 inch diameter wire
      was bonded to enamel using conventional orthodontic adhesive (Transbond LR, 3M
      Unitek) and ACP-containing composite (Aegis Ortho, Harry J. Bosworth Co.), with
      or without the use of a primer. The specimens were sealed with nail varnish,
      stained with 0.5 per cent basic fuchsine for 24 hours, sectioned and examined
      under a stereomicroscope, and scored for microleakage at the composite-enamel and
      composite-wire interfaces from the mesial and distal margins. Statistical
      analyses were performed with Kruskal-Wallis and Mann-Whitney U-tests with a
      Bonferroni correction. Little or no microleakage was observed between the
      composite-enamel interface for any of the three groups, and any difference was
      not statistically significant. The amount of microleakage at the wire-composite
      interface was higher than that at the enamel-composite interface. Multiple
      comparison testing showed statistically significant differences in microleakage
      between Transbond LR and the ACP-containing adhesive used with primer at the
      composite-enamel and composite-wire interfaces (P < 0.001). ACP-containing
      adhesive used with primer showed the highest microleakage scores at the composite
      enamel (mean: 0.39 +/- 0.42 mm) and composite-wire (mean: 1.66 +/- 0.47 mm)
      interfaces. The hypothesis is rejected. The ACP-containing composite used with or
      without primer showed significantly higher leakage at the composite-wire
      interface, while conventional lingual retainer composite showed lower
      microleakage scores.

PMID- 19858076
TI  - Microleakage between composite-wire and composite-enamel interfaces of flexible
      spiral wire retainers. Part 1: comparison of three composites.
AB  - The aim of this investigation was to test the hypothesis that there is no
      difference in microleakage between composite-enamel and composite-wire
      interfaces, when different composites are used. Forty-five freshly extracted
      human mandibular incisors separated into three groups were used in the study.
      Multi-stranded 0.0215 inch diameter wire was bonded to enamel using two
      conventional (Transbond XT and Transbond LR) and a flowable (Venus Flow)
      orthodontic composite. The specimens were sealed with nail varnish, stained with
      0.5 per cent basic fuchsine for 24 hours, sectioned and examined under a
      stereomicroscope, and scored for microleakage at the composite-enamel and
      composite-wire interfaces from the mesial and distal margins. Statistical
      analysis was performed using Kruskal-Wallis and Mann-Whitney U-tests with a
      Bonferroni correction. Little or no microleakage was observed between the
      composite-enamel interfaces for the three investigated composites, and any
      difference was not statistically significant. However, statistically significant
      differences were found between microleakage at the composite-wire interface for
      both the conventional and flowable composite groups (P < 0.001). Flowable
      composite showed the highest leakage (mean: 4.8 +/- 0.8 mm), while Transbond XT
      (mean: 0.5 +/- 0.3 mm) and Transbond LR (mean: 1.1 +/- 1.2 mm) showed
      significantly lower and comparable results. The amount of microleakage at the
      wire-composite interface was significantly greater than that at the enamel
      composite interface of flexible spiral wire retainers (FSWRs). The null
      hypothesis is therefore rejected. Flowable composites may not be appropriate for
      bonding FSWRs.

PMID- 19858077
TI  - What influences the uptake of information to prevent skin cancer? A systematic
      review and synthesis of qualitative research.
AB  - Skin cancer is an increasing problem in Europe, America and Australasia, although
      largely preventable by avoiding excessive ultraviolet (UV) exposure. This paper
      presents the findings of a systematic review of qualitative research about the
      prevention of skin cancer attributable to UV exposure. The aim is to understand
      elements that may contribute to the successful or unsuccessful conveyance of skin
      cancer prevention messages and their uptake by the public. A systematic review
      was undertaken using evidence identified through searching electronic
      bibliographic databases and Web sites and reference list checks. Predefined
      inclusion and exclusion criteria were used. Sixteen study reports (relating to 15
      separate studies) were included from the United Kingdom, United States,
      Australia, Canada and New Zealand. Each included study was quality appraised, and
      the findings were extracted into an evidence table. A coding scheme, framed by
      the Health Belief Model, was developed by the reviewers and informed analysis and
      synthesis. This showed that most people perceived their susceptibility to skin
      cancer, and its severity, as low. While benefits of adopting changed behaviour
      were acknowledged, there were substantial barriers to this, including positive
      perceptions of a tan as healthy and attractive and the hassle of covering up or
      using sunscreen. Peers, parents and media may offer 'cues to action' that
      encourage adoption of preventative behaviour and finally self-efficacy or the
      perceived ability to make such changes. Effective health education messages will
      need to address the barriers to adopting protective behaviours identified through
      this review.

PMID- 19858078
TI  - Cerebrospinal hypocretin, daytime sleepiness and sleep architecture in
      Parkinson's disease dementia.
AB  - Excessive daytime sleepiness is common in Parkinson's disease and has been
      associated with Parkinson's disease-related dementia. Narcoleptic features have
      been observed in Parkinson's disease patients with excessive daytime sleepiness
      and hypocretin cell loss has been found in the hypothalamus of Parkinson's
      disease patients, in association with advanced disease. However, studies on
      cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinson's disease have
      been inconclusive. Reports of sleep studies in Parkinson's disease patients with
      and without excessive daytime sleepiness have also been disparate, pointing
      towards a variety of causes underlying excessive daytime sleepiness. In this
      study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinson's
      disease patients with and without dementia and to study their relationship to
      dementia and clinical excessive daytime sleepiness, as well as to describe
      potentially related sleep architecture changes. Twenty-one Parkinson's disease
      patients without dementia and 20 Parkinson's disease patients with dementia,
      along with 22 control subjects without sleep complaints, were included. Both
      Epworth sleepiness scale, obtained with the help of the caregivers, and mini
      mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1
      levels were measured in all individuals using a radio-immunoassay technique.
      Additionally, eight Parkinson's disease patients without dementia and seven
      Parkinson's disease patients with dementia underwent video-polysomnogram and
      multiple sleep latencies test. Epworth sleepiness scale scores were higher in
      Parkinson's disease patients without dementia and Parkinson's disease patients
      with dementia than controls (P < 0.01) and scores >10 were more frequent in
      Parkinson's disease patients with dementia than in Parkinson's disease patients
      without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar
      among groups (controls = 321.15 +/- 47.15 pg/ml; without dementia = 300.99 +/-
      58.68 pg/ml; with dementia = 309.94 +/- 65.95 pg/ml; P = 0.67), and unrelated to
      either epworth sleepiness scale or mini-mental state examination. Dominant
      occipital frequency awake was slower in Parkinson's disease patients with
      dementia than Parkinson's disease patients without dementia (P = 0.05). Presence
      of slow dominant occipital frequency and/or loss of normal non-rapid eye movement
      sleep architecture was more frequent among Parkinson's disease patients with
      dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in
      Parkinson's disease patients with dementia than Parkinson's disease patients
      without dementia, but lumbar cerebrospinal fluid hypocretin-1 levels are normal
      and unrelated to severity of sleepiness or the cognitive status. Lumbar
      cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to
      occur in the hypothalamus of advanced Parkinson's disease. Alternatively,
      mechanisms other than hypocretin cells dysfunction may be responsible for
      excessive daytime sleepiness and the sleep architecture alterations seen in these
      patients.

PMID- 19858080
TI  - The ratio of 'deleted in colorectal cancer' to 'uncoordinated-5A' netrin-1
      receptors on the growth cone regulates mossy fibre directionality.
AB  - Proper axonal targeting is fundamental to the establishment of functional neural
      circuits. The hippocampal mossy fibres normally project towards the CA3 region.
      In the hippocampi of patients with temporal lobe epilepsy and related animal
      models, however, mossy fibres project towards the molecular layer and produce the
      hyperexcitable recurrent networks. The cellular and molecular mechanisms
      underlying this aberrant axonal targeting, known as mossy fibre sprouting, remain
      unclear. Netrin-1 attracts or repels axons depending on the composition of its
      attraction-mediating receptor, deleted in colorectal cancer, and its repulsion
      mediating receptor, uncoordinated-5, on the growth cone; but the roles of netrin
      1-dependent guidance in pathological conditions are largely unknown. In this
      study, we examined the role of netrin-1 and its receptors in mossy fibre guidance
      and report that enhanced neuronal activity changes netrin-1-mediated cell
      targeting by the axons under hyperexcitable conditions. Netrin-1 antibody or Dcc
      ribonucleic acid interference attenuated mossy fibre growth towards CA3 in slice
      overlay assays. The axons were repelled from CA3 and ultimately innervated the
      molecular layer when hyperactivity was pharmacologically introduced. We first
      hypothesized that a reduction in netrin-1 expression in CA3 underlies the
      phenomenon, but found that its expression was increased. We then examined two
      possible activity-dependent changes in netrin-1 receptor expression: a reduction
      in the deleted in colorectal cancer receptor and induction of uncoordinated-5
      receptor. Hyperactivity did not affect the surface expression of the deleted in
      colorectal cancer receptor on the growth cone, but it increased that of
      uncoordinated-5A, which was suppressed by blocking cyclic adenosine monophosphate
      signalling. In addition, Dcc knockdown did not affect hyperactivity-induced mossy
      fibre sprouting in the slice cultures, whereas Unc5a knockdown rescued the
      mistargeting. Thus, netrin-1 appears to attract mossy fibres via the deleted in
      colorectal cancer receptor, while it repels them via cyclic adenosine
      monophosphate-induced uncoordinated-5A under hyperexcitable conditions, resulting
      in mossy fibre sprouting.

PMID- 19858081
TI  - Posterior cingulate hypometabolism in early Alzheimer's disease: what is the
      contribution of local atrophy versus disconnection?

PMID- 19858082
TI  - Acute aortic dissection during sorafenib-containing therapy.

PMID- 19858083
TI  - Management of occult invasive cervical cancer found after simple hysterectomy.
AB  - BACKGROUND: To estimate safety and efficacy of radical parametrectomy (RP) and
      radiation therapy (RT) or concurrent chemoradiation therapy (CCRT) for patients
      with occult invasive cervical cancer found after simple hysterectomy. MATERIALS
      AND METHODS: We retrospectively evaluated outcomes in 147 patients with occult
      invasive cervical cancer. RESULTS: Forty-eight patients with IA1 lesions (IA1
      group) did not receive further treatment. Of the 99 patients with IA2-IIA
      lesions, 26 received no definitive treatment (observation group), 44 received RT
      or CCRT (RT/CCRT group), and 29 underwent RP (RP group). After a median follow-up
      of 116 months (range 3-235 months), recurrent disease was observed in 0%, 34.6%,
      6.8%, and 0% of patients in the IA1, observation, RT/CCRT, and RP groups,
      respectively. In the RT/CCRT group, treatment was delayed due to severe diarrhea
      in 4 patients (9%) and 12 patients (27%) had late complications related to RT
      requiring further management (including two surgical interventions). Five
      patients in the RP group (17%) experienced perioperative complications which were
      easily managed, intraoperatively or conservatively. Late complications were not
      observed in the RP group. CONCLUSION: Although RP and RT/CCRT had similar
      therapeutic efficacy, the lower rate of late complications observed with RP makes
      it preferable to RT/CCRT.

PMID- 19858084
TI  - Subcutaneous 'lipoma-like' B-cell lymphoma associated with HCV infection: a new
      presentation of primary extranodal marginal zone B-cell lymphoma of MALT.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection has been linked to
      lymphoproliferative disorders. Marginal zone B-cell lymphoma (MZL) represents one
      of the most frequent lymphoma subtypes associated with HCV infection. We describe
      an unusual subset of HCV-associated MZL characterized by subcutaneous
      presentation. MATERIALS AND METHODS: A series of 12 HCV-positive patients
      presenting with subcutaneous nodules that revealed lymphoma infiltration at
      biopsy. Molecular analysis of immunoglobulin heavy chain (IGH) gene rearrangement
      and FISH investigations for t(11;18)(q21;q21) and t(14;18)(q32;q21) were carried
      out in nine patients. RESULTS: The 12 patients (median age 69.5 years), all with
      positive HCV serology, presented with single or multiple subcutaneous nodules
      resembling lipomas. Histologically the lesions showed lymphoid infiltrates,
      consistent with extranodal MZL of mucosa-associated lymphoid tissue (MALT).
      Functional IGH gene rearrangements were identified in nine tested patients, with
      somatic mutations in 82%, indicating a histogenesis from germinal center
      experienced B cells. The t(11;18) was found in two of nine cases. Staging did not
      show any other lymphoma localization. In two patients, a response was achieved
      with antiviral treatment. Extracutaneous spread to MALT sites occurred in a case.
      CONCLUSIONS: Our observations expand the spectrum of HCV-associated lymphomas to
      include a subset of extranodal MZL characterized by a novel primary 'lipoma-like'
      subcutaneous presentation and indolent clinical course.

PMID- 19858085
TI  - Characteristics of cancer patients using homeopathy compared with those in
      conventional care: a cross-sectional study.
AB  - BACKGROUND: There are only few studies on cancer patients who are treated in
      complementary and alternative medicine clinics and comparing them with patients
      in conventional care. We will present the comparison of characteristics of two
      patient cohorts: one was treated in a homeopathic cancer care clinic and one was
      treated in a conventional oncology care (CC) outpatient clinic. PATIENTS AND
      METHODS: Six-hundred and forty-seven patients were included in this cross
      sectional cohort study and had to fill in questionnaires [health-related quality
      of life (QoL) (Functional Assessment of Cancer Therapy-General Scale), depression
      and anxiety (Hospital Anxiety and Depression Scale), fatigue (Multidimensional
      Fatigue Inventory) and expectancies toward treatment]. Clinical data were
      extracted from medical records. This study presents the comparison of both
      cohorts. RESULTS: Patients in the homeopathy cohort are younger, better educated
      and more often employed than patients in the CC cohort. The most pronounced
      differences indicate longer disease histories and different diagnostic and
      clinical pretreatment variables. Despite the clinical differences, QoL as well as
      anxiety, depression and fatigue was similar in both the groups. CONCLUSIONS:
      Homeopathic treatment is sought by cancer patients at a different phase during
      the course of the disease, which has particular implications for research.
      However, expectancies toward the benefit of the treatment as well as QoL data are
      similar.

PMID- 19858086
TI  - Increasing incidence rates of soft tissue sarcomas? A population-based
      epidemiologic study and literature review.
AB  - BACKGROUND: Increasing incidence rates of soft tissue sarcomas (STS) have been
      reported. In the present study, the authors have analyzed the incidence of STS in
      Austria in a population-based study for the period 1984-2004. PATIENTS AND
      METHODS: Age-adjusted incidence rates, gender and age predilection and geographic
      differences were analyzed, comprising data from the Austrian National Cancer
      Registry. RESULTS: A total of 5333 cases were registered; male-to-female ratio
      was 0.8. The most common histotypes were sarcoma not otherwise specified (36%),
      leiomyosarcoma (24%), liposarcoma (12%), malignant fibrous histiocytoma (9%) and
      fibrosarcoma (5%). Age-adjusted incidence rate was 2.4 per 100,000 per year.
      Analysis of annual incidence rates and 3-year periods showed no increase (annual
      increasing gradient = -0.0025). CONCLUSIONS: This study has analyzed the most
      recent data from a European population in comparison with seven international
      studies. An increase, as postulated elsewhere, could not be confirmed. The
      incidence rate of STS in Austria ranges in the lower half of the international
      incidence rates (1.8-5.0 per 100,000 per year). Different inclusion criteria
      (Kaposi's sarcoma and dermatofibrosarcoma) and classifications in the various
      studies explain the increase of incidence in some studies rather than true
      increase of STS due to new or accumulated risk factors.

PMID- 19858087
TI  - Low-dose tamoxifen in the treatment of breast ductal intraepithelial neoplasia:
      results of a large observational study.
AB  - BACKGROUND: Tamoxifen's cost-benefit ratio for breast ductal intraepithelial
      neoplasia (DIN) is unclear. Since low-dose tamoxifen showed a favorable
      modulation of breast cancer biomarkers in phase II trials, a monoinstitutional
      cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment
      was analyzed. PATIENTS AND METHODS: A total of 309 patients with DIN received low
      dose tamoxifen as part of institutional guidelines and were compared with 371
      patients with DIN who received no systemic treatment after surgery. RESULTS:
      Women with estrogen receptor (ER)/progesterone receptor (PgR) >50% DIN who were
      not treated had a higher incidence of breast events than women on tamoxifen
      [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00-3.12] or women with
      ER/PgR <50% DIN (HR 1.72; 95% CI 1.14-2.58). Among untreated patients with ER
      >50% DIN, recurrence was higher in PgR > or =50% DIN than in PgR <50% DIN,
      whereas it was similar among low PgR (<50%) DIN against which tamoxifen had no
      effect. No difference in endometrial cancer incidence was noted. CONCLUSIONS:
      High ER and especially high PgR expression is a significant adverse prognostic
      indicator of DIN, and low-dose tamoxifen appears to be an active treatment. Women
      with low-expression ER or PgR DIN do not seem to benefit from tamoxifen. A
      definitive clinical trial is warranted.

PMID- 19858089
TI  - Identification and management of psychosocial problems among toddlers by
      preventive child health care professionals.
AB  - BACKGROUND: Objective of this study was to assess the degree to which preventive
      child health professionals (CHPs) identify and act upon psychosocial problems
      among young toddlers in the general population and to determine the concordance
      with parent-reported behavioural and emotional problems. Also, associations of
      psychosocial problems with socio-demographic factors, and (mental) health history
      of the toddlers were studied. METHODS: CHPs examined a national sample of
      children aged 14 months and interviewed their parents during the routine health
      assessments. Identification of and action upon psychosocial problems by CHPs were
      registered. The Infant-Toddler Social and Emotional Assessment (ITSEA) was
      completed by the parents. Data were available on 701 Dutch 14-month-old toddlers.
      RESULTS: In 7.6% of all toddlers, CHPs identified one or more psychosocial
      problems. Forty-seven percent of identified children were referred to another
      professional or received follow-up. Identification of psychosocial problems and
      subsequent action were 3-16 times more likely in children with clinical parent
      reported problem behaviour according to the Dutch adapted version of the ITSEA.
      Also, past or current professional care for psychosocial problems was associated
      with the CHPs' identification or action. Associations with socio-demographic
      variables were weak. CONCLUSION: The CHPs frequently identify psychosocial
      problems in 14-month-old toddlers, but they miss many cases of parent-reported
      problems as measured by a clinical ITSEA score. This general population study
      shows substantial room for improvement in the early identification of
      psychosocial problems in young toddlers.

PMID- 19858088
TI  - Quantitative analysis of changes in ER, PR and HER2 expression in primary breast
      cancer and paired nodal metastases.
AB  - BACKGROUND: Assessment of receptors [estrogen receptor (ER), progesterone
      receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely
      carried out on primary tumour in order to select appropriate adjuvant therapy;
      the same analysis is not carried out on nodal metastases. Since de novo
      resistance to therapy is common, we quantified differences in receptor expression
      between primary and nodal disease in order to assess whether this might
      contribute to therapeutic resistance. PATIENTS AND METHODS: A total of 385
      patients with invasive primary breast carcinomas and paired lymph nodes (n = 211)
      were assessed for ER, PR and HER2 expression using quantitative
      immunofluorescence. Cut-points were defined by comparison with tumours scored by
      immunohistochemistry (IHC) and FISH. Differences in expression for each of the
      markers and molecular phenotype were analysed. RESULTS: Quantitative receptor
      expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had
      disparate breast/node receptor status of at least one receptor. Many of the
      differences in expression between primary tumour and node are large magnitude
      (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of
      cases. CONCLUSIONS: A significant number of patients show discordant quantitative
      expression of molecular markers between primary and nodal disease. Appropriately
      measured, lymph node receptor status could be a more accurate measurement for
      guiding adjuvant therapy, which requires testing in a clinical trial.

PMID- 19858090
TI  - Prevention and social constructivism.

PMID- 19858091
TI  - Fibre width measurement and quantification of filler size distribution in paper
      based materials by SEM and image analysis.
AB  - In this paper the development of image processing and analysis routines for
      acquiring information about the paper structure from images obtained by scanning
      electron microscopy (SEM) is described. A new method to measure the fibre width
      based on the processing of superficial SEM observation is herein proposed and
      successfully applied to some commercial paper-based materials. The quantification
      of fillers in the Z-direction of paper was based on paper cross-sectional SEM
      images. The results obtained by image processing demonstrated the excellent
      performance and suitability of the proposed method to quantify exactly
      information concerning fraction and size distribution of digital fillers. The
      fraction of digital fillers was correlated with the surface roughness of a given
      paper grade.

PMID- 19858092
TI  - Increased adenosine contributes to penile fibrosis, a dangerous feature of
      priapism, via A2B adenosine receptor signaling.
AB  - Priapism is a condition of persistent penile erection in the absence of sexual
      excitation. Of men with sickle cell disease (SCD), 40% display priapism. The
      disorder is a dangerous and urgent condition, given its association with penile
      fibrosis and eventual erectile dysfunction. Current strategies to prevent its
      progression are poor because of a lack of fundamental understanding of the
      molecular mechanisms for penile fibrosis in priapism. Here we demonstrate that
      increased adenosine is a novel causative factor contributing to penile fibrosis
      in two independent animal models of priapism, adenosine deaminase (ADA)-deficient
      mice and SCD transgenic mice. An important finding is that chronic reduction of
      adenosine by ADA enzyme therapy successfully attenuated penile fibrosis in both
      mouse models, indicating an essential role of increased adenosine in penile
      fibrosis and a novel therapeutic possibility for this serious complication.
      Subsequently, we identified that both mice models share a similar fibrotic gene
      expression profile in penile tissue (including procollagen I, TGF-beta(1), and
      plasminogen activator inhibitor-1 mRNA), suggesting that they share similar
      signaling pathways for progression to penile fibrosis. Thus, in an effort to
      decipher specific cell types and underlying mechanism responsible for adenosine
      mediated penile fibrosis, we purified corpus cavernosal fibroblast cells (CCFCs),
      the major cell type involved in this process, from wild-type mice. Quantitative
      RT-PCR showed that the major receptor expressed in these cells is the adenosine
      receptor A(2B)R. Based on this fact, we further purified CCFCs from A(2B)R
      deficient mice and demonstrated that A(2B)R is essential for excess adenosine
      mediated penile fibrosis. Finally, we revealed that TGF-beta functions downstream
      of the A(2B)R to increase CCFC collagen secretion and proliferation. Overall, our
      studies identify an essential role of increased adenosine in the pathogenesis of
      penile fibrosis via A(2B)R signaling and offer a potential target for prevention
      and treatment of penile fibrosis, a dangerous complication seen in priapism.-Wen,
      J., Jiang, X., Dai, Y., Zhang, Y., Tang, Y., Sun, H., Mi, T., Phatarpekar, P. V.,
      Kellems, R. E., Blackburn, M. R., Xia, Y. Increased adenosine contributes to
      penile fibrosis, a dangerous feature of priapism, via A(2B) adenosine receptor
      signaling.

PMID- 19858093
TI  - Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine
      phosphatase and a transcription factor.
AB  - Eya proteins are transcription factors that play pivotal roles in organ formation
      during development by mediating interactions between Sine Oculis (SO) and
      Dachshund (DAC). Remarkably, the transcriptional activity of Eya proteins is
      regulated by a dephosphorylating activity within its Eya domain (ED). However,
      the molecular basis for the link between catalytic and transcriptional activities
      remains unclear. Here we report the first description of the crystal structure of
      the ED of human Eya2 (ED-Eya2), determined at 2.4-A resolution. In stark contrast
      to other members of the haloacid dehalogenase (HAD) family to which ED-Eya2
      belongs, the helix-bundle motif (HBM) is elongated along the back of the
      catalytic site. This not only results in a structure that accommodates large
      protein substrates but also positions the catalytic and the SO-interacting sites
      on opposite faces, which suggests that SO binding is not directly affected by
      catalytic function. Based on the observation that the DAC-binding site is located
      between the catalytic core and SO binding sites within ED-Eya2, we propose that
      catalytic activity can be translated to SO binding through DAC, which acts as a
      transcriptional switch. We also captured at two stages of reaction cycles-acyl
      phosphate intermediate and transition state of hydrolysis step, which provided a
      detailed view of reaction mechanism. The ED-Eya2 structure defined here serves as
      a model for other members of the Eya family and provides a framework for
      understanding the role of Eya phosphatase mutations in disease.

PMID- 19858094
TI  - A versatile system for the neuronal subtype specific expression of lentiviral
      vectors.
AB  - Lentiviral expression vectors are powerful tools for gene therapy and long-term
      gene expression/repression in the mammalian brain. However, no specificity of
      transduction has been reported so far in the central nervous system. Here we have
      developed a novel system to achieve a neuronal subtype specific expression in
      either dopaminergic (DA) or GABAergic neurons. We employed a delivery strategy by
      which the transgene is not expressed until its activation by Cre recombinase. We
      successfully tested the system in vitro and then used this novel lentivector,
      containing loxP sites, in 2 different transgenic mouse lines expressing Cre
      either in DA or in GABAergic neurons. In both lines the reporter gene was
      detected exclusively in Cre-positive cells, demonstrating that with this
      experimental approach we were able to achieve completely specific expression of
      transgenes delivered by lentiviral vectors. This universal system can be applied
      to all neural subtypes making use of the growing number of specific Cre driver
      lines.- Tolu, S., Avale, M. E., Nakatani, H., Pons, S., Parnaudeau, S., Tronche,
      F., Vogt, A., Monyer, H., Vogel, R., de Chaumont, F., Olivo-Marin, J.-C.,
      Changeux, J.-P., Maskos, U. A versatile system for the neuronal subtype specific
      expression of lentiviral vectors.

PMID- 19858095
TI  - Activated protein C utilizes the angiopoietin/Tie2 axis to promote endothelial
      barrier function.
AB  - Activated protein C (APC) is an anticoagulant, approved as a treatment for severe
      sepsis, that can prevent apoptosis, inflammation, and vascular leakage. The aim
      of this study was to investigate whether APC protects endothelial barrier
      function through the angiopoietin (Ang)/Tie2 axis. APC significantly up-regulated
      gene and protein expression of Tie2 and Ang1 in a dose (0.01-10 microg/ml)- and
      time (0.5-24 h)-dependent manner in human umbilical vein endothelial cells
      (HUVECs). Interestingly, it markedly inhibited Ang2 with an IC(50) of
      approximately 0.1 microg/ml. HUVEC permeability, measured using Evans blue dye
      transfer, was significantly reduced in the presence of APC, and, in concordance,
      the tight junction associated protein zona occludens (ZO)-1 was up-regulated and
      localized peripherally around cells, compared with controls. Smooth muscle cell
      migration toward APC-stimulated HUVECs was elevated compared with unstimulated
      cells. Blocking antibodies and small interfering (si) RNA treatment, compared
      with isotype (IgG) or scrambled siRNA controls, showed that APC requires 3
      receptors, the endothelial protein C receptor, protease-activated receptor 1, and
      Tie2 to perform all these barrier stabilization functions. In summary, this study
      demonstrates that APC has novel effects on the Ang/Tie2 axis, which enhance
      endothelial barrier function and are likely to contribute to its therapeutic
      effect in sepsis and other diseases associated with vascular leakage.-Minhas, N.,
      Xue, M., Fukudome, K., Jackson, C. J. Activated protein C utilizes the
      angiopoietin/Tie2 axis to promote endothelial barrier function.

PMID- 19858097
TI  - The signaling pathway leading to extracellular signal-regulated kinase 5 (ERK5)
      activation via G-proteins and ERK5-dependent neurotrophic effects.
AB  - Extracellular signal-regulated kinases (ERKs) or mitogen-activated protein
      kinases (MAPKs) are involved in cellular proliferation, differentiation,
      migration, and gene expression. The MAPK family includes ERK1/2, c-Jun NH(2)
      terminal kinases 1, 2, and 3, p38MAPK alpha, beta, gamma, and -delta, and ERK5 as
      conventional MAPKs and ERK3, ERK4 NLK, and ERK7 as atypical MAPKs. Like other
      MAPKs, ERK5 is activated by variety of stimuli, including growth factors, G
      protein-coupled receptor (GPCR) agonists, cytokines, and stress. However, the
      signaling pathway leading to ERK5 activation is not well understood compared with
      the other conventional MAPKs. For example, the pharmacological reagents that
      induce second messenger cAMP and Ca(2+) downstream of GPCRs do not activate ERK5
      in neuronal cells. In addition, conflicting results have come from studies
      examining the involvement of small G-proteins in ERK5 activation by growth
      factors, and the details of the signaling pathway remain controversial. In
      addition, the physiological roles of ERK5 in neuronal cells have not been
      clarified. One reason was the lack of a selective ERK5 pharmacological inhibitor
      until the novel selective MEK5/ERK5 inhibitors BIX02188 and BIX02189 (Biochem
      Biophys Res Commun 377:120-125, 2008) reported last year. Another reason is that
      the use of interfering mutants is limited in neuronal cells because the
      transfection efficiency is low. Despite these difficulties, recent studies
      suggest that ERK5 mediates the promotion of neuronal survival and neuronal
      differentiation in vitro and in vivo. In this review, the signaling pathway
      leading to ERK5 activation through heterotrimeric and small G-proteins and the
      physiological roles of ERK5 in neuronal cells are summarized and discussed.

PMID- 19858096
TI  - Lymphangiogenesis and angiogenesis: concurrence and/or dependence? Studies in
      inbred mouse strains.
AB  - Genetic background significantly affects angiogenesis in mice. However,
      lymphangiogenic response to growth factors (GFs) in different strains has not
      been studied. We report constitutive expression of corneal lymphatics that
      extends beyond the limits of normal limbal vessels. In untreated corneas, the
      total number (P=0.006), the number above blood vessels (P=10(-8)), and the area
      of preexisting lymphatics (P=0.007) were significantly higher in C57BL/6 than in
      BALB/c mice. Normal corneas of three other strains, the nu/nu, 129E, and Black
      Swiss mice, showed in most parameters intermediate phenotypes. FGF-2(-/-) mice
      showed significantly less preexisting lymphatics than control (P=0.009), which
      suggests a role for this GF in lymphatic development. VEGF-A-induced corneal
      lymphangiogenic response was significantly higher in BALB/c mice (P=0.03), but it
      did not differ significantly in C57BL/6 mice, when compared to PBS-implanted
      control. FGFR-3 expression was higher in C57BL/6 than BALB/c mice, which suggests
      GF-receptor heterogeneity as a possible explanation for strain-dependent
      differences. The heterogeneity of preexisting lymphatic vessels in the limbal
      area significantly correlated with the extent of corneal lymphangiogenesis (VEGF
      A: r=0.7, P=0.01; FGF-2: r=0.96, P=10(-5)) in BALB/c but not in C57BL/6 mice.
      Removal of conjunctival lymphatics did not affect GF-induced lymphangiogenesis.
      This work introduces physiological expression of lymphatics without blood
      vessels, which indicates that angiogenesis and lymphangiogenesis, even though
      intricately related, may occur independently. Furthermore, we show strain
      dependence of normal and GF-induced lymphangiogenesis. These differences may
      affect disease development in various strains.

PMID- 19858098
TI  - Megx.net: integrated database resource for marine ecological genomics.
AB  - Megx.net is a database and portal that provides integrated access to
      georeferenced marker genes, environment data and marine genome and metagenome
      projects for microbial ecological genomics. All data are stored in the Microbial
      Ecological Genomics DataBase (MegDB), which is subdivided to hold both sequence
      and habitat data and global environmental data layers. The extended system
      provides access to several hundreds of genomes and metagenomes from prokaryotes
      and phages, as well as over a million small and large subunit ribosomal RNA
      sequences. With the refined Genes Mapserver, all data can be interactively
      visualized on a world map and statistics describing environmental parameters can
      be calculated. Sequence entries have been curated to comply with the proposed
      minimal standards for genomes and metagenomes (MIGS/MIMS) of the Genomic
      Standards Consortium. Access to data is facilitated by Web Services. The updated
      megx.net portal offers microbial ecologists greatly enhanced database content,
      and new features and tools for data analysis, all of which are freely accessible
      from our webpage http://www.megx.net.

PMID- 19858099
TI  - PDBe: Protein Data Bank in Europe.
AB  - The Protein Data Bank in Europe (PDBe) (http://www.ebi.ac.uk/pdbe/) is actively
      working with its Worldwide Protein Data Bank partners to enhance the quality and
      consistency of the international archive of bio-macromolecular structure data,
      the Protein Data Bank (PDB). PDBe also works closely with its collaborators at
      the European Bioinformatics Institute and the scientific community around the
      world to enhance its databases and services by adding curated and actively
      maintained derived data to the existing structural data in the PDB. We have
      developed a new database infrastructure based on the remediated PDB archive data
      and a specially designed database for storing information on interactions between
      proteins and bound molecules. The group has developed new services that allow
      users to carry out simple textual queries or more complex 3D structure-based
      queries. The newly designed 'PDBeView Atlas pages' provide an overview of an
      individual PDB entry in a user-friendly layout and serve as a starting point to
      further explore the information available in the PDBe database. PDBe's active
      involvement with the X-ray crystallography, Nuclear Magnetic Resonance
      spectroscopy and cryo-Electron Microscopy communities have resulted in improved
      tools for structure deposition and analysis.

PMID- 19858100
TI  - Telomeric circles are abundant in the stn1-M1 mutant that maintains its telomeres
      through recombination.
AB  - Some human cancers maintain their telomeres using the alternative lengthening of
      telomeres (ALT) mechanism; a process thought to involve recombination. Different
      types of recombinational telomere elongation pathways have been identified in
      yeasts. In senescing yeast telomerase deletion (ter1-Delta) mutants with very
      short telomeres, it has been hypothesized that copying a tiny telomeric circle (t
      circle) by a rolling circle mechanism is the key event in telomere elongation. In
      other cases more closely resembling ALT cells, such as the stn1-M1 mutant of
      Kluyveromyces lactis, the telomeres appear to be continuously unstable and
      routinely reach very large sizes. By employing two-dimensional gel
      electrophoresis and electron microscopy, we show that stn1-M1 cells contain
      abundant double stranded t-circles ranging from approximately 100 to 30,000 bp in
      size. We also observed small single-stranded t-circles, specifically composed of
      the G-rich telomeric strand and tailed circles resembling rolling circle
      replication intermediates. The t-circles most likely arose from recombination
      events that also resulted in telomere truncations. The findings strengthen the
      possibility that t-circles contribute to telomere maintenance in stn1-M1 and ALT
      cells.

PMID- 19858101
TI  - Transposition of the human Hsmar1 transposon: rate-limiting steps and the
      importance of the flanking TA dinucleotide in second strand cleavage.
AB  - Hsmar1 is a member of the mariner family of DNA transposons. Although widespread
      in nature, their molecular mechanism remains obscure. Many other cut-and-paste
      elements use a hairpin intermediate to cleave the two strands of DNA at each
      transposon end. However, this intermediate is absent in mariner, suggesting that
      these elements use a fundamentally different mechanism for second-strand
      cleavage. We have taken advantage of the faithful and efficient in vitro reaction
      provided by Hsmar1 to characterize the products and intermediates of
      transposition. We report different factors that particularly affect the reaction,
      which are the reaction pH and the transposase concentration. Kinetic analysis
      revealed that first-strand nicking and integration are rapid. The rate of the
      reaction is limited in part by the divalent metal ion-dependent assembly of a
      complex between transposase and the transposon end(s) prior to the first
      catalytic step. Second-strand cleavage is the rate-limiting catalytic step of the
      reaction. We discuss our data in light of a model for the two metal ion catalytic
      mechanism and propose that mariner excision involves a significant conformational
      change between first- and second-strand cleavage at each transposon end.
      Furthermore, this conformational change requires specific contacts between
      transposase and the flanking TA dinucleotide.

PMID- 19858102
TI  - Martini: using literature keywords to compare gene sets.
AB  - Life scientists are often interested to compare two gene sets to gain insight
      into differences between two distinct, but related, phenotypes or conditions.
      Several tools have been developed for comparing gene sets, most of which find
      Gene Ontology (GO) terms that are significantly over-represented in one gene set.
      However, such tools often return GO terms that are too generic or too few to be
      informative. Here, we present Martini, an easy-to-use tool for comparing gene
      sets. Martini is based, not on GO, but on keywords extracted from Medline
      abstracts; Martini also supports a much wider range of species than comparable
      tools. To evaluate Martini we created a benchmark based on the human cell cycle,
      and we tested several comparable tools (CoPub, FatiGO, Marmite and ProfCom).
      Martini had the best benchmark performance, delivering a more detailed and
      accurate description of function. Martini also gave best or equal performance
      with three other datasets (related to Arabidopsis, melanoma and ovarian cancer),
      suggesting that Martini represents an advance in the automated comparison of gene
      sets. In agreement with previous studies, our results further suggest that
      literature-derived keywords are a richer source of gene-function information than
      GO annotations. Martini is freely available at http://martini.embl.de.

PMID- 19858103
TI  - PlnTFDB: updated content and new features of the plant transcription factor
      database.
AB  - The Plant Transcription Factor Database (PlnTFDB; http://plntfdb.bio.uni
      potsdam.de/v3.0/) is an integrative database that provides putatively complete
      sets of transcription factors (TFs) and other transcriptional regulators (TRs) in
      plant species (sensu lato) whose genomes have been completely sequenced and
      annotated. The complete sets of 84 families of TFs and TRs from 19 species
      ranging from unicellular red and green algae to angiosperms are included in
      PlnTFDB, representing >1.6 billion years of evolution of gene regulatory
      networks. For each gene family, a basic description is provided that is
      complemented by literature references, and multiple sequence alignments of
      protein domains. TF or TR gene entries include information of expressed sequence
      tags, 3D protein structures of homologous proteins, domain architecture and cross
      links to other computational resources online. Moreover, the different species in
      PlnTFDB are linked to each other by means of orthologous genes facilitating cross
      species comparisons.

PMID- 19858104
TI  - PROSITE, a protein domain database for functional characterization and
      annotation.
AB  - PROSITE consists of documentation entries describing protein domains, families
      and functional sites, as well as associated patterns and profiles to identify
      them. It is complemented by ProRule, a collection of rules based on profiles and
      patterns, which increases the discriminatory power of these profiles and patterns
      by providing additional information about functionally and/or structurally
      critical amino acids. PROSITE is largely used for the annotation of domain
      features of UniProtKB/Swiss-Prot entries. Among the 983 (DNA-binding) domains,
      repeats and zinc fingers present in Swiss-Prot (release 57.8 of 22 September
      2009), 696 ( approximately 70%) are annotated with PROSITE descriptors using
      information from ProRule. In order to allow better functional characterization of
      domains, PROSITE developments focus on subfamily specific profiles and a new
      profile building method giving more weight to functionally important residues.
      Here, we describe AMSA, an annotated multiple sequence alignment format used to
      build a new generation of generalized profiles, the migration of ScanProsite to
      Vital-IT, a cluster of 633 CPUs, and the adoption of the Distributed Annotation
      System (DAS) to facilitate PROSITE data integration and interchange with other
      sources. The latest version of PROSITE (release 20.54, of 22 September 2009)
      contains 1308 patterns, 863 profiles and 869 ProRules. PROSITE is accessible at:
      http://www.expasy.org/prosite/.

PMID- 19858106
TI  - Modelling relative survival in the presence of incomplete data: a tutorial.
AB  - BACKGROUND: Missing data frequently create problems in the analysis of population
      based data sets, such as those collected by cancer registries. Restriction of
      analysis to records with complete data may yield inferences that are
      substantially different from those that would have been obtained had no data been
      missing. 'Naive' methods for handling missing data, such as restriction of the
      analysis to complete records or creation of a 'missing' category, have drawbacks
      that can invalidate the conclusions from the analysis. We offer a tutorial on
      modern methods for handling missing data in relative survival analysis. METHODS:
      We estimated relative survival for 29 563 colorectal cancer patients who were
      diagnosed between 1997 and 2004 and registered in the North West Cancer
      Intelligence Service. The method of multiple imputation (MI) was applied to
      account for the common example of incomplete stage at diagnosis, under the
      missing at random (MAR) assumption. Multivariable regression with a generalized
      linear model and Poisson error structure was then used to estimate the excess
      hazard of death of the colorectal cancer patients, over and above the background
      mortality, adjusting for significant predictors of mortality. RESULTS: Incomplete
      information on stage, morphology and grade meant that only 55% of the data could
      be included in the 'complete-case' analysis. All cases could be included after
      indicator method (IM) or MI method. Handling missing data by MI produced a
      significantly lower estimate of the excess mortality for stage, morphology and
      grade, with the largest reductions occurring for late-stage and high-grade
      tumours, when compared with the results of complete-case analysis. CONCLUSION: In
      complete-case analysis, almost 50% of the information could not be included, and
      with the IM, all records with missing values for stage were combined into a
      single 'missing' category. We show that MI methods greatly improved the results
      by exploiting all the information in the incomplete records. This method also
      helped to ensure efficient inferences about survival were made from the
      multivariate regression analyses.

PMID- 19858105
TI  - Molecular crowding creates an essential environment for the formation of stable G
      quadruplexes in long double-stranded DNA.
AB  - Large numbers of guanine-rich sequences with potential to form G-quadruplexes
      have been identified in genomes of various organisms. Such sequences are
      constrained at both ends by long DNA duplex with a complementary strand in close
      proximity to compete for duplex formation. G-quadruplex/duplex competition in
      long double-stranded DNA has rarely been studied. In this work, we used DMS
      footprinting and gel electrophoresis to study G-quadruplex formation in long
      double-stranded DNA derived from human genome under both dilute and molecular
      crowding condition created by PEG. G-quadruplex formation was observed in the
      process of RNA transcription and after heat denaturation/renaturation under
      molecular crowding condition. Our results showed that the heat
      denaturation/renaturation treatment followed by gel electrophoresis could provide
      a simple method to quantitatively access the ability of G-quadruplex formation in
      long double-stranded DNA. The effect of K(+) and PEG concentration was
      investigated and we found that stable G-quadruplexes could only form under the
      crowding condition with PEG at concentrations near the physiological
      concentration of biomass in living cells. This observation reveals a physical
      basis for the formation of stable G-quadruplexes in genome and supports its
      presence under the in vivo molecular crowding condition.

PMID- 19858107
TI  - The shared signal hypothesis and neural responses to expressions and gaze in
      infants and adults.
AB  - Event-related potentials were recorded from adults and 4-month-old infants while
      they watched pictures of faces that varied in emotional expression (happy and
      fearful) and in gaze direction (direct or averted). Results indicate that
      emotional expression is temporally independent of gaze direction processing at
      early stages of processing, and only become integrated at later latencies. Facial
      expressions affected the face-sensitive ERP components in both adults (N170) and
      infants (N290 and P400), while gaze direction and the interaction between facial
      expression and gaze affected the posterior channels in adults and the
      frontocentral channels in infants. Specifically, in adults, this interaction
      reflected a greater responsiveness to fearful expressions with averted gaze
      (avoidance-oriented emotion), and to happy faces with direct gaze (approach
      oriented emotions). In infants, a larger activation to a happy expression at the
      frontocentral negative component (Nc) was found, and planned comparisons showed
      that it was due to the direct gaze condition. Taken together, these results
      support the shared signal hypothesis in adults, but only to a lesser extent in
      infants, suggesting that experience could play an important role.

PMID- 19858108
TI  - Serotonin transporter genotype modulates amygdala activity during mood
      regulation.
AB  - Recent studies have implicated the short allele of the serotonin transporter
      linked polymorphic region (5-HTTLPR) in depression vulnerability, particularly in
      the context of stress. Several neuroimaging studies have shown that 5-HTTLPR
      genotype predicts amygdala reactivity to negatively valenced stimuli, suggesting
      a mechanism whereby the short allele confers depression risk. The current study
      investigated whether 5-HTTLPR genotype similarly affects neural activity during
      an induced sad mood and during recovery from sad mood. Participants were 15
      homozygous short (S) and 15 homozygous long (L) individuals. Regional cerebral
      blood flow was measured with perfusion functional magnetic resonance imaging
      during four scanning blocks: baseline, sad mood, mood recovery and following
      return to baseline. Comparing mood recovery to baseline, both whole brain
      analyses and template-based region-of-interest analyses revealed greater amygdala
      activity for the S vs the L-group. There were no significant amygdala differences
      found during the induced sad mood. These results demonstrate the effect of the S
      allele on amygdala activity during intentional mood regulation and suggest that
      amygdala hyperactivity during recovery from a sad mood may be one mechanism by
      which the S allele confers depression risk.

PMID- 19858109
TI  - Medical complications of an aquatic innovation.
AB  - The sport of swimming has been affected by the innovations of technology with the
      evolution of the swimsuit. The health benefits of swimming are numerous and are
      well documented in the scientific literature. As swimming is a low-impact sport,
      injuries are relatively uncommon. As a direct result of the new swimsuits, team
      physicians have identified the emergence of a new trend in injury in the aquatic
      athlete. Extensive blistering and ulceration of the finger tips and distal
      interphalangeal joints in addition to ecchymoses of the lower limb are now common
      in the aquatic athlete wearing the new swimsuits. Team physicians working with
      elite swimmers should be aware of this phenomenon and institute preventive
      measures.

PMID- 19858110
TI  - Setting standards for the prevention and management of travellers' diarrhoea in
      elite athletes: an audit of one team during the Youth Commonwealth Games in
      India.
AB  - OBJECTIVE: Devise and implement evidence-based guidelines for the prevention and
      management of travellers' diarrhoea (TD), and establish the incidence of TD
      during an elite sporting trip to India. DESIGN: Literature review and audit.
      SETTING: Youth Commonwealth Games in India 2008. PARTICIPANTS: All members of the
      Team England Squad. MAIN OUTCOME MEASURES: Hygiene guidelines included only
      drinking bottled water, eating hot food and regular hand washing with alcohol
      gel. Ciprofloxacin was offered to non-athlete team members as prophylaxis but not
      to athletes due to its possible association with tendon disease. Following
      implementation of these guidelines, the incidence of travellers' diarrhoea (TD)
      in the whole squad was 24/122 (20%), compared with 7/14 (50%) on the
      reconnaissance trip (preguidelines). In those taking prophylactic ciprofloxacin,
      the incidence was 4/33 (12%), compared with 20/89 (23%) in those not taking
      ciprofloxacin. No athlete missed their event due to TD. CONCLUSIONS: The
      incidence of TD was less during the event than on the reconnaissance trip. The
      relative contribution to this reduction in strict hygiene guidelines as compared
      with potentially improved catering hygiene arrangements is unknown. Prophylactic
      ciprofloxacin also reduced the incidence of TD but it is probably not appropriate
      for use in elite athletes. Rifaximin may be an alternative for this group.

PMID- 19858111
TI  - ECG as a part of the preparticipation screening programme: an old and still
      present international dilemma.
AB  - INTRODUCTION: Long-term Italian experience has provided evidence that
      preparticipation screening in competitive athletes with 12-lead ECG, history and
      physical examination is effective in identifying potentially lethal
      cardiovascular diseases. However, it is not being routinely practised in other
      countries. OBJECTIVES: To evaluate the usefulness of a preparticipation screening
      programme in a sample of players belonging to different disciplines. MATERIAL AND
      METHODS: From September 2006 to June 2008, 1220 young athletes from different
      sports disciplines underwent a cardiovascular examination that included personal
      and family history, physical examination and a resting 12-lead ECG. Those with
      abnormal findings were referred for additional tests. RESULTS: 1220 Athletes were
      screened: 96% males; mean age 23 (4) years. 90 (7.4%) players were referred for
      additional tests because of abnormal findings on baseline examination: 11 (0.9%)
      personal or family history, 4 (0.08%) physical examination and 75 (6.14%) 12-lead
      ECG. Echocardiographic assessment fulfilled left ventricular hypertrophy criteria
      in 8 of the 90 players. Of those, one case was considered an athlete's heart and
      one case was diagnosed with hypertrophic cardiomyopathy (septal thickness 23 mm).
      Further tests were needed in the remaining six, included in the "grey area", with
      one additional case of hypertrophic cardiomyopathy (apical variant) suggested by
      cardiac MRI. CONCLUSION: Given the ability of 12-lead ECG to detect individuals
      with structural heart disease, we suggest its inclusion as a part of
      preparticipation screening programmes.

PMID- 19858112
TI  - The effect of non-contingent and accurate performance feedback on pacing and time
      trial performance in 4-km track cycling.
AB  - OBJECTIVE: To determine whether the provision of comparative performance feedback
      during 4 km track cycling affects completion time. DESIGN: Five highly trained
      male cyclists first performed a baseline (BL) 4-km time trial (TT) on a velodrome
      track, followed by two further randomised 4-km TT, during which riders received
      either correct (COR) or non-contingent (FAL) feedback based on their BL
      performance. RESULTS: Participants completed the COR TT in a significantly faster
      time (t(4)=-3.10, p<0.05) than the FAL TT (341 (8) s vs 350 (12) s). Over the TT,
      a significant difference in mean speed was apparent between the two conditions
      (F(15,60)=1.95, p<0.05) on the second (t(4)=4.71, p<0.05), 15th (t(4)=3.45,
      p<0.05) and final lap (t(4)=3.30, p<0.05). CONCLUSION: The significant difference
      in completion time and pacing strategy between the two conditions suggests that
      accurate, comparative performance feedback is beneficial to performance,
      especially during the start and end of an exercise bout. The results support the
      previously unfounded assumption that performance feedback is advantageous during
      exercise and highlights the importance of an athlete's support team during an
      event.

PMID- 19858113
TI  - Violence in youth sports: hazing, brawling and foul play.
AB  - By separating hazing, brawling, and foul play and failing to recognise that their
      connection to sport binds them together into a cohesive subset of sport injury
      and youth violence, past research has failed to show how sports-related violence
      is a broad example of interpersonal violence. The acceptance of violence within
      the sporting culture may, in part, explain why sports-related violence has not
      yet been widely recognised as a public health concern. This review shows that
      sports-related violence, including hazing, brawling and foul play, occurs among
      youth athletes of all ages and in a variety of different sports. The few studies
      to address this issue have all acknowledged the dangers of sports-related
      violence; however, no incident tracking method has been developed. Future
      research must provide accurate national estimates of the incidence of sports
      related violence among youth, identify associated risk factors, evaluate
      preventive interventions and identify effective methods of distributing and
      implementing evidence-based interventions. Monitoring the magnitude and
      distribution of the burden of sports-related violence and building the scientific
      infrastructure necessary to support the development and widespread application of
      effective sports-related prevention interventions are essential first steps
      toward a reduction in the incidence of sports-related violence.

PMID- 19858114
TI  - Sex differences in force attenuation: a clinical assessment of single-leg hop
      performance on a portable force plate.
AB  - OBJECTIVE: Impaired biomechanics and neuromuscular control have been suggested as
      probable links to female sex bias in the onset of patellofemoral pain syndrome.
      There are limited objective, clinical measures for assessment of impaired
      biomechanics and neuromuscular control. The primary objective of this
      investigation was to examine sex differences in vertical ground reaction force
      (vGRF) and force loading rate in young athletes performing maximum, repeated
      vertical single-leg hops (RVSHs). The authors hypothesised that females would
      demonstrate greater vGRF and force loading rate than males and show interlimb
      differences in force attenuation. DESIGN: Cross-sectional study. SETTING:
      Paediatric sports medicine clinic. PARTICIPANTS: 109 Healthy high school, soccer
      and basketball athletes. ASSESSMENT OF RISK FACTORS: Participants performed RVSHs
      for 15 seconds on a portable force plate with a sampling rate of 400 Hz
      (Accupower; AMTI, Watertown, Massachusetts, USA). MAIN OUTCOME MEASUREMENTS: Raw
      vGRF was filtered with a generalised cross-validation spline using a 50-Hz cutoff
      frequency and then normalised to potential energy. Force loading rate was
      calculated by dividing normalised vGRF by time-to-peak force. Group means were
      compared using analysis of variance. RESULTS: The females demonstrated
      significantly greater normalised vGRF (p<0.001) and force loading rate (p<0.001)
      during landing than their male counterparts. Neither sex demonstrated significant
      interlimb differences in force attenuation (p>0.05). CONCLUSIONS: The female
      athletes may have altered force attenuation capability during RVSHs as identified
      by increased vGRF and force loading rate compared with the male athletes.
      Portable force plates may be potential tools to identify altered force
      attenuation in clinical settings.

PMID- 19858115
TI  - Heat injury in youth sport.
AB  - Heat injury is a potentially lethal condition that is considered to be completely
      preventable. Fatal heat injury is relatively rare (0.20 per 100 000 player
      seasons in US high school football) and there are very limited data on non-fatal
      incidence. Expert recommendations for prevention include gradual acclimatisation
      of youth athletes to hot conditions, reductions in activity in hot and humid
      conditions, wearing light and light-coloured clothing, careful monitoring of
      athletes for signs of heat injury to facilitate immediate detection, having the
      resources to immediately and rapidly cool affected athletes, and education of
      athletes, care givers, and coaches about heat injury. Although a base of
      observational case data, physiological information, and expert opinion exists,
      the science surrounding this field is devoid of health communication and health
      behaviour research, and there is a pressing need for analytical studies to
      evaluate intervention programmes and/or identify new risk factors. There is also
      a need for ongoing data collection on heat injury incidence and on the knowledge,
      attitudes and behaviours towards heat injury among youth athletes, their care
      givers and their coaches.

PMID- 19858116
TI  - Wheat (Triticum aestivum) NAM proteins regulate the translocation of iron, zinc,
      and nitrogen compounds from vegetative tissues to grain.
AB  - The NAM-B1 gene is a NAC transcription factor that affects grain nutrient
      concentrations in wheat (Triticum aestivum). An RNAi line with reduced expression
      of NAM genes has lower grain protein, iron (Fe), and zinc (Zn) concentrations. To
      determine whether decreased remobilization, lower plant uptake, or decreased
      partitioning to grain are responsible for this phenotype, mineral dynamics were
      quantified in wheat tissues throughout grain development. Control and RNAi wheat
      were grown in potting mix and hydroponics. Mineral (Ca, Cu, Fe, K, Mg, Mn, P, S,
      and Zn) and nitrogen (N) contents of organs were determined at regular intervals
      to quantify the net remobilization from vegetative tissues and the accumulation
      of nutrients in grain. Total nutrient accumulation was similar between lines, but
      grain Fe, Zn, and N were at lower concentrations in the NAM knockdown line. In
      potting mix, net remobilization of N, Fe, and Zn from vegetative tissues was
      impaired in the RNAi line. In hydroponics with ample nutrients, net
      remobilization was not observed, but grain Fe and Zn contents and concentrations
      remained lower in the RNAi line. When Fe or Zn was withheld post-anthesis, both
      lines demonstrated remobilization. These results suggest that a major effect of
      the NAM genes is an increased efflux of nutrients from the vegetative tissues and
      a higher partitioning of nutrients to grain.

PMID- 19858117
TI  - Aluminium-induced inhibition of root elongation in Arabidopsis is mediated by
      ethylene and auxin.
AB  - Aluminium (Al) is phytotoxic when solubilized into Al(3+) in acidic soils. One of
      the earliest and distinct symptoms of Al(3+) toxicity is inhibition of root
      elongation. To decipher the mechanism by which Al(3+) inhibits root elongation,
      the role of ethylene and auxin in Al(3+)-induced inhibition of root elongation in
      Arabidopsis thaliana was investigated using the wild type and mutants defective
      in ethylene signalling (etr1-3 and ein2-1) and auxin polar transport (aux1-7 and
      pin2). Exposure of wild-type Arabidopsis to AlCl(3) led to a marked inhibition of
      root elongation, and elicited a rapid ethylene evolution and enhanced activity of
      the ethylene reporter EBS:GUS in root apices. Root elongation in etr1-3 and ein2
      1 mutants was less inhibited by Al(3+) than that in wild-type plants. Ethylene
      synthesis inhibitors, Co(2+) and aminoethoxyvinylglycine (AVG), and an antagonist
      of ethylene perception (Ag(+)) abolished the Al(3+)-induced inhibition of root
      elongation. There was less inhibition of root elongation by Al(3+) in aux1-7 and
      pin2 mutants than in the wild type. The auxin polar transport inhibitor,
      naphthylphthalamic acid (NPA), substantially alleviated the Al(3+)-induced
      inhibition of root elongation. The Al(3+) and ethylene synthesis precursor
      aminocyclopropane carboxylic acid (ACC) increased auxin reporter DR5:GUS activity
      in roots. The Al(3+)-induced increase in DR5:GUS activity was reduced by AVG,
      while the Al(3+)-induced increase in EBS:GUS activity was not altered by NPA.
      Al(3+) and ACC increased transcripts of AUX1 and PIN2, and this effect was no
      longer observed in the presence of AVG and Co(2+). These findings indicate that
      Al(3+)-induced ethylene production is likely to act as a signal to alter auxin
      distribution in roots by disrupting AUX1- and PIN2-mediated auxin polar
      transport, leading to arrest of root elongation.

PMID- 19858119
TI  - Comment on: Hepatotoxicity rates do not differ in patients with rheumatoid
      arthritis and psoriasis treated with methotrexate.

PMID- 19858118
TI  - Physiological and proteomic approaches to address heat tolerance during anthesis
      in rice (Oryza sativa L.).
AB  - Episodes of high temperature at anthesis, which in rice is the most sensitive
      stage to temperature, are expected to occur more frequently in future climates.
      The morphology of the reproductive organs and pollen number, and changes in
      anther protein expression, were studied in response to high temperature at
      anthesis in three rice (Oryza sativa L.) genotypes. Plants were exposed to 6 h of
      high (38 degrees C) and control (29 degrees C) temperature at anthesis and
      spikelets collected for morphological and proteomic analysis. Moroberekan was the
      most heat-sensitive genotype (18% spikelet fertility at 38 degrees C), while IR64
      (48%) and N22 (71%) were moderately and highly heat tolerant, respectively. There
      were significant differences among the genotypes in anther length and width,
      apical and basal pore lengths, apical pore area, and stigma and pistil length.
      Temperature also affected some of these traits, increasing anther pore size and
      reducing stigma length. Nonetheless, variation in the number of pollen on the
      stigma could not be related to measured morphological traits. Variation in
      spikelet fertility was highly correlated (r=0.97, n=6) with the proportion of
      spikelets with > or = 20 germinated pollen grains on the stigma. A 2D-gel
      electrophoresis showed 46 protein spots changing in abundance, of which 13
      differentially expressed protein spots were analysed by MS/MALDI-TOF. A cold and
      a heat shock protein were found significantly up-regulated in N22, and this may
      have contributed to the greater heat tolerance of N22. The role of differentially
      expressed proteins and morphology during anther dehiscence and pollination in
      shaping heat tolerance and susceptibility is discussed.

PMID- 19858120
TI  - Arterial stiffness and cumulative inflammatory burden in rheumatoid arthritis: a
      dose-response relationship independent of established cardiovascular risk
      factors.
AB  - OBJECTIVE: To quantify the relationship between arterial stiffness and cumulative
      inflammatory burden in patients with RA. METHODS: We recruited RA patients
      without overt arterial disease aged 40-65 years, attending hospital rheumatology
      outpatient clinics. Standardized research nurse assessment included blood
      pressure (BP), pulse wave analysis (PWA, SphygmoCor), BMI, fasting blood sample
      (lipids, glucose, RF and ESR), patient questionnaire (smoking, alcohol, diet,
      exercise, family history of premature coronary heart disease and Stanford HAQ),
      current medication and medical record review. Cumulative inflammatory burden was
      measured as ESR area-under-the-curve (ESR-years) extracted from medical records.
      Arterial stiffness was measured using PWA [aortic augmentation index (AIX@75)].
      Multiple linear regression was used to adjust for age, sex and nine other
      cardiovascular risk factors. RESULTS: We recruited 114 RA patients (mean age 54
      years, female 81%, current DMARD 90%, current NSAID 70%, ACR criteria 56%)
      comprising 1040 RA person-years. Cholesterol, glucose and BMI were similar in
      women and men. Women had a longer duration of arthritis (10 vs 7 years) and were
      more likely to be seropositive (85 vs 71%). BP, smoking and alcohol consumption
      were lower for women. On fully adjusted analysis, an increase of 100 ESR-years
      was associated with an increase in AIX@75 of 0.51 (95% CI 0.13, 0.88). On fully
      adjusted analysis restricted to women the increase was 0.43 (95% CI 0.01, 0.85).
      CONCLUSIONS: In RA patients free of overt arterial disease, a dose-response
      relationship exists between cumulative inflammatory burden and arterial
      stiffness. This relationship is independent of established CV risk factors.

PMID- 19858122
TI  - Cardiovascular morbidity and mortality remain similar in two cohorts of patients
      with long-standing rheumatoid arthritis seen in 1978 and 1995 in Malmo, Sweden.
AB  - OBJECTIVE: Patients with RA have an increased risk of cardiovascular disease.
      Management of RA has changed substantially over time. Our aim was to evaluate
      changes in cardiovascular morbidity and mortality over the period of 1978-2002.
      METHODS: Two cohorts of consecutive patients with RA seen at outpatient clinics
      in Malmo, Sweden, were started in 1978 (n = 148) and 1995 (n = 161) and compared
      with the corresponding background population. Patients were followed for 8 years,
      and fatal and non-fatal cardiovascular first events were identified using two
      national registers, hospital discharge and cause of death. Standardized morbidity
      ratio (SMoR) and standardized mortality ratio (SMR), adjusted for age and sex
      were calculated. RESULTS: Sex distribution, age at disease onset and disease
      duration were similar in both groups. The 1995 cohort was more extensively
      treated with DMARDs and had less disease activity and disability. Total
      cardiovascular morbidity was increased in the 1978 cohort (SMoR 158; 95% CI 111,
      225) as well as in the 1995 cohort (SMoR 168; 95% CI 118, 232). This was mainly
      due to an increased risk of coronary artery disease. Overall mortality was
      elevated in the 1978 cohort but not in the 1995 cohort. There was no change in
      cardiovascular excess mortality (SMR 175; 95% CI 100, 284; and 172; 100, 276 for
      the two cohorts, respectively). CONCLUSIONS: There were similar elevations in the
      incidence of cardiovascular comorbidity in RA patients, identified two decades
      apart compared with the general population, in spite of more extensive treatment
      and reduced disease severity in the more recent cohort.

PMID- 19858123
TI  - The effect of reminder letters on the uptake of an e-learning programme on
      dementia: a randomized trial in general practice.
AB  - BACKGROUND AND AIMS: The aim of the present study was to evaluate whether three
      reminder letters mailed to GPs after dissemination of a Dementia Guideline
      increased the GPs' use of the corresponding e-learning programme (ELP). METHODS:
      Single-blinded randomized trial among all GPs in Copenhagen Municipality from 1
      November 2006 to 1 May 2007. RESULTS: A total of 15 of 320 GPs (4.7%) had a web
      based logon during the study period. The intervention group had a significantly
      increased frequency of web-based logons (P = 0.0192) equivalent to a hazard ratio
      of 8.0 (95% CI: 1.03-66.1; P = 0.047). NNT was calculated to 22.2. We could not
      detect any significant differences in any of the secondary outcomes. CONCLUSIONS:
      Three reminder letters added to a nation-wide dissemination increased the
      probability for a GP logon in the ELP by a Factor 8. However, in total, only a
      small proportion used the ELP. Thus, further research is needed in order to
      consider future implementation strategies for Internet-based Continuous Medical
      Education activities among not primed GPs.

PMID- 19858121
TI  - Fibrocyte activation in rheumatoid arthritis.
AB  - OBJECTIVES: RA is a common, relapsing autoimmune disease primarily affecting the
      joints. Fibroblast-like synovial (FLS) cells are thought to be responsible for
      pannus formation and secretion of factors that recruit leucocytes to affected
      joints, thereby promoting bone and cartilage destruction. Fibrocytes are
      multipotent circulating stem cells that may have a role in RA pathogenesis,
      perhaps as the precursors of the FLS cells, or by regulating FLS cell function.
      METHODS: We utilized multidimensional phospho-specific flow cytometry to
      characterize the activation status of peripheral blood (PB) fibrocytes derived
      from human RA patients at different stages of disease and from mice with CIA.
      RESULTS: Human PB fibrocytes from RA patients exhibited phosporylation activation
      of the p44/42 and p38 MAP kinases (MAPKs), and STAT3 (signal transducer and
      activator of transcription) and STAT-5 early in disease, within the first year of
      diagnosis. Similarly, in murine CIA, an increase in the total number of PB
      phosphoSTAT5-positive fibrocytes was observed at early time points in disease.
      Notably, in the affected paws of mice with CIA, we identified an increased number
      of fibrocytes, in contrast to the paws of control mice. CONCLUSIONS: These data
      suggest that activated fibrocytes may influence the disease process in RA and may
      serve as surrogate markers for disease in the PB of affected patients.

PMID- 19858124
TI  - Pharmacists and nurses as independent prescribers: exploring the patient's
      perspective.
AB  - BACKGROUND: Little is known about patients' opinions upon the development of non
      medical prescribing (NMP). OBJECTIVE: To explore the opinions of patients on the
      development of NMP. METHODS: In-depth interviews using qualitative methodology
      (Interpretative Phenomological Analysis). Eighteen interviews were undertaken in
      Bristol (Sites 1 and 3), Swindon (Site 2) and Brighton (Site 4). [Site 1 =
      primary care, GP prescriber (n = 5), Site 2 = secondary care, consultant
      prescriber (n = 5), Site 3 = primary care (n = 5) and Site 4 = secondary care (n
      = 3) (both pharmacist supplementary prescribers.] Participants (n = 18) were
      randomly sampled from patients under the care of the participating prescriber.
      Participants were aged between 42 and 81 years of age (n = 11 male and n = 7
      female). Interviews took place between January and August 2006. RESULTS:
      Participants expressed concerns about clinical governance, privacy and whether
      sufficient space were available to provide the service in community pharmacies.
      Participants acknowledged the expert drug knowledge of pharmacists and their
      accessibility. These factors enhanced acceptability of this role for pharmacists.
      Nurses were highly regarded, accepted and preferred as prescribers with few
      concerns. CONCLUSIONS: The results indicate support for pharmacists and nurses as
      prescribers, which aid successful implementation. Further research may be needed
      to evaluate the level of understanding that the public has of NMP and their views
      of the service once NMP is more widely established. Stakeholders should be
      mindful that the public may be hesitant regarding the professionalism, quality
      and clinical governance standards of clinics in community pharmacies in
      particular.

PMID- 19858125
TI  - Work problems due to low back pain: what do GPs do? A questionnaire survey.
AB  - BACKGROUND: Low back pain can affect work ability and remains a main cause of
      sickness absence. In the UK the GP is usually the first contact for patients
      seeking health care. The UK government intends that the GP will continue to be
      responsible for sickness certification and work advice. This role requires a
      considerable level of understanding of work rehabilitation, and effective
      communication between GPs, patients, employers and therapists. OBJECTIVES: The
      aim of this study was to identify GPs' current practice in managing patients
      whose ability to work is affected by low back pain, and their perception of the
      support services required. METHOD: A postal questionnaire of 441 GPs in the South
      Nottinghamshire area of the UK was carried out. Areas covered included referral
      patterns, sickness certification, and communication with therapists and
      employers. RESULTS: There was a 54.6% response rate. The majority of GPs (76.8%)
      reported that they did not take overall responsibility for managing the work
      problems of patients arising from low back pain. Few 'mainly agreed' that they
      initiated communication with employers (2.5%) and/or therapists (10.4%) regarding
      their patients' work. CONCLUSION: The results of this study demonstrate that most
      GPs do not readily engage in vocational rehabilitation and do not initiate
      contact with employers or other health care practitioners regarding patients'
      work problems. Thus the current government expectation that GPs are able to
      successfully manage this role may be unrealistic; considerable training and a
      change in the GPs' perception of their role will be required.

PMID- 19858126
TI  - Young people and their GP: a register-based study of 1717 Norwegian GPs.
AB  - BACKGROUND: Internationally, there has been a call to improve the youth
      friendliness of health services. In surveys, 60-90% of young people report having
      contact with a GP at least once a year. Regular contact with the GP can be
      assumed to be an indicator of a youth-friendly health service. The aim of the
      current study was to identify associations between a high consultation rate with
      young people (15-24 years) on the one hand and GP characteristics, patient list
      characteristics and practice profiling factors on the other. METHODS: A cross
      sectional national register-based study from 2002-04 in Norwegian general
      practice. Data on 1717 GPs, their practice populations and a sample of 316 773
      consultations with young people were used to estimate differences between GPs,
      using one-way analysis of variance and logistic regression. RESULTS: The mean
      annual consultation rate with young people was 1.4 (95% confidence interval 1.4
      1.5) and 2.2 (2.1-2.2) for the age groups 15-19 and 20-24, respectively. List
      characteristics indicating free capacity-a shorter patient list, a growing
      patient list and a high access for persons not on the patient list-were
      associated with a high youth consultation rate. Young age of the GP, low
      educational level among the list population and a high rate of interdisciplinary
      activity by the GP were also associated with a high youth consultation rate.
      CONCLUSIONS: GPs seem to assign especially low priority to young people when
      workload is high or free capacity low. Increased awareness of these mechanisms
      and greater interdisciplinary cooperation could increase the youth-friendliness
      of general practice.

PMID- 19858127
TI  - Unexpected myopathy associated with a mutation in MYBPC3 and misplacement of the
      cardiac myosin binding protein C.
AB  - BACKGROUND: Myosin binding protein C (MyBPC) is essential for the structure of
      the sarcomeres in striated muscle. There is one cardiac specific isoform and two
      skeletal muscle specific isoforms. Mutations in MYBPC3 encoding the cardiac
      isoform cause cardiomyopathy. METHODS AND RESULTS: We have identified an infant
      with fatal cardiomyopathy due to a homozygous mutation, p.R943X, in MYBPC3. The
      patient also had an unexpected skeletal myopathy. The patient expressed the
      cardiac specific MyBPC isoform in skeletal muscle at transcript and protein
      levels. Numerous muscle fibres expressing the mutant cardiac isoform showed
      structural abnormalities with disorganisation of sarcomeres and depletion of
      myosin thick filaments. CONCLUSIONS: The surprising identification of a skeletal
      myopathy in this patient was due to aberrant expression of mutant cardiac MyBPC
      in skeletal muscle.

PMID- 19858128
TI  - Clinical and molecular characterisation of Bardet-Biedl syndrome in
      consanguineous populations: the power of homozygosity mapping.
AB  - Bardet-Biedl syndrome (BBS) is a ciliopathy with pleiotropic effect that
      manifests primarily as renal insufficiency, polydactyly, retinal dystrophy and
      obesity. The current phenotype-genotype correlation is insufficient to predict
      the likely causative mutation that makes sequencing of all 14 BBS genes an often
      necessary but highly complicated way to identify the underlying genetic defect in
      affected patients. In this study, homozygosity mapping is shown as a robust
      approach that is highly suited for genetically heterogeneous autosomal recessive
      disorders in populations in which consanguinity is prevalent. This approach
      allowed us to quickly identify seven novel mutations in seven families with BBS.
      Some of these mutations would have been missed by unguided routine sequencing,
      which suggests that missed mutations in known BBS genes could be more common than
      previously thought. This study, the largest to date on Saudi BBS families, also
      revealed interesting phenotypic aspects of BBS, including the first report of non
      syndromic retinitis pigmentosa as a novel BBS phenotype.

PMID- 19858129
TI  - Coexistence of two different pseudohypoparathyroidism subtypes (Ia and Ib) in the
      same kindred with independent Gs{alpha} coding mutations and GNAS imprinting
      defects.
AB  - BACKGROUND: Pseudohypoparathyroidism (PHP) defines a rare group of disorders
      whose common feature is resistance to the parathyroid hormone. Patients with PHP
      Ia display additional hormone resistance, Albright hereditary osteodystrophy
      (AHO) and reduced Gsalpha activity in easily accessible cells. This form of PHP
      is associated with heterozygous inactivating mutations in Gsalpha-coding exons of
      GNAS, an imprinted gene locus on chromosome 20q13.3. Patients with PHP-Ib
      typically have isolated parathyroid hormone resistance, lack AHO features and
      demonstrate normal erythrocyte Gsalpha activity. Instead of coding Gsalpha
      mutations, patients with PHP-Ib display imprinting defects of GNAS, caused, at
      least in some cases, by genetic mutations within or nearby this gene. PATIENTS:
      Two unrelated PHP families, each of which includes at least one patient with a
      Gsalpha coding mutation and another with GNAS loss of imprinting, are reported
      here. RESULTS: One of the patients with GNAS imprinting defects has paternal
      uniparental isodisomy of chromosome 20q, explaining the observed imprinting
      abnormalities. The identified Gsalpha coding mutations include a tetranucleotide
      deletion in exon 7, which is frequently found in PHP-Ia, and a novel single
      nucleotide change at the acceptor splice junction of intron 11. CONCLUSIONS:
      These molecular data reveal an interesting mixture, in the same family, of both
      genetic and epigenetic mutations of the same gene.

PMID- 19858131
TI  - Epidemiology as the foundation for population and men's health.

PMID- 19858130
TI  - Karyomapping: a universal method for genome wide analysis of genetic disease
      based on mapping crossovers between parental haplotypes.
AB  - The use of genome wide single nucleotide polymorphism (SNP) arrays for high
      resolution molecular cytogenetic analysis using a combination of quantitative and
      genotype analysis is well established. This study demonstrates that by Mendelian
      analysis of the SNP genotypes of the parents and a sibling or other appropriate
      family member to establish phase, it is possible to identify informative loci for
      each of the four parental haplotypes across each chromosome and map the
      inheritance of these haplotypes and the position of any crossovers in the
      proband. The resulting 'karyomap', unlike a karyotype, identifies the parental
      and grandparental origin of each chromosome and chromosome segment and is unique
      for every individual being defined by the independent segregation of parental
      chromosomes and the pattern of non-recombinant and recombinant chromosomes.
      Karyomapping, therefore, enables both genome wide linkage based analysis of
      inheritance and detection of chromosome imbalance where either both haplotypes
      from one parent are present (trisomy) or neither are present (monosomy/deletion).
      The study also demonstrates that karyomapping is possible at the single cell
      level following whole genome amplification and, without any prior patient or
      disease specific test development, provides a universal linkage based methodology
      for preimplantation genetic diagnosis readily available worldwide.

PMID- 19858132
TI  - Clopidogrel and calcium-channel blockers: a clinically important interaction?

PMID- 19858133
TI  - Strategies to screen and reduce vascular risk--putting statins in the tap water
      is not the answer.

PMID- 19858134
TI  - Combined non-invasive anatomical and functional assessment with MSCT and MRI for
      the detection of significant coronary artery disease in patients with an
      intermediate pre-test likelihood.
AB  - OBJECTIVES: To compare magnetic resonance myocardial perfusion imaging (MRI) with
      anatomical assessment by multislice computed tomography (MSCT) coronary
      angiography and conventional coronary angiography. DESIGN AND PATIENTS: In this
      prospective study, 53 patients (60% male, average age 57+/-9 years, 83%
      intermediate pre-test likelihood) underwent 1.5 T MRI, 64-slice MSCT and
      conventional coronary angiography. MAIN OUTCOME MEASURES: The presence of
      significant stenosis (>or=50% luminal narrowing) was determined on MSCT and
      conventional coronary angiography. Ischaemia on MRI was defined as a stress
      perfusion abnormality in the absence of delayed contrast enhancement. RESULTS: A
      significant stenosis was seen on MSCT in 15 (28%) patients, while ischaemia on
      MRI was seen in 19 (36%). In the 38 patients without significant stenosis on
      MSCT, normal perfusion was seen in 29 (76%). In patients with a significant
      stenosis on MSCT, ischaemia was seen in 10 (67%). In all patients without
      significant stenosis on MSCT and normal perfusion on MRI (n=29), significant
      stenosis was absent on conventional coronary angiography. All patients with both
      MSCT and MRI abnormal (n=10) had significant stenoses on conventional coronary
      angiography. CONCLUSION: The anatomical and functional data obtained with MSCT
      and MRI are complementary for the assessment of coronary artery disease. These
      findings support the sequential or combined assessment of anatomy and function.

PMID- 19858135
TI  - Six-minute walk test: independent prognostic marker?

PMID- 19858136
TI  - Infarct size and left ventricular function in the PRoximal Embolic Protection in
      Acute myocardial infarction and Resolution of ST-segment Elevation (PREPARE)
      trial: ancillary cardiovascular magnetic resonance study.
AB  - OBJECTIVES: The aim of the study was to evaluate whether primary percutaneous
      coronary intervention (PCI) with combined proximal embolic protection and
      thrombus aspiration results in smaller final infarct size and improved left
      ventricular function assessed by cardiovascular magnetic resonance (CMR) in ST
      segment elevation myocardial infarction (STEMI) patients compared with primary
      PCI alone. Background Primary PCI with the Proxis system improves immediate
      microvascular flow post-procedure as measured by ST-segment resolution, which
      could result in better outcomes. METHODS: The ancillary CMR study included 206
      STEMI patients who were enrolled in the PRoximal Embolic Protection in Acute
      myocardial infarction and Resolution of ST-Elevation (PREPARE) trial. CMR imaging
      was assessed between 4 and 6 months after the index procedure. RESULTS: There
      were no significant differences in final infarct size (6.1 g/m(2) vs 6.3 g/m(2),
      p = 0.78) and left ventricular ejection fraction (50% vs 50%, p = 0.46) between
      both groups. Also, systolic wall thickening in the infarct area (44% vs 45%, p =
      0.93) or the extent of transmural segments (8.3% of segments vs 8.3% of segments,
      p = 0.60) showed no significant differences. The incidence of major adverse
      cardiac and cerebral events at 6 months was similar in the Proxis and control
      group (8% vs 10%, respectively, p = 0.43). Conclusions Primary PCI with combined
      proximal embolic protection and thrombus aspiration in STEMI patients did not
      result in significant differences in final infarct size or left ventricular
      function at follow-up CMR. In addition, there was no difference in the incidence
      of major adverse cardiac and cerebral events at 6 months. TRIAL REGISTRATION:
      number ISRCTN71104460.

PMID- 19858137
TI  - Left ventricular twist mechanics in patients with apical hypertrophic
      cardiomyopathy: assessment with 2D speckle tracking echocardiography.
AB  - OBJECTIVE: Left ventricular (LV) apical rotation significantly contributes to LV
      twist, which has been reported to have a vital role in maintaining LV systolic
      and diastolic function. Apical hypertrophic cardiomyopathy (ApHCM) is a unique
      disease with pathological LV hypertrophy at the apex. We aimed (1) to evaluate LV
      twist mechanics in ApHCM and (2) to demonstrate the influence of predominantly
      local, pathological involvement of the apical myocardium on LV twist mechanics.
      METHODS: 21 patients diagnosed with ApHCM were consecutively enrolled and
      compared with normal controls. After a standard echocardiographic examination, we
      scanned parasternal basal and apical short-axis planes to quantify LV rotations
      and LV twist using the speckle tracking technique. For better understanding of LV
      twist mechanics in ApHCM, LV radial and biplanar strains and LV twist-volume
      curve were also evaluated. RESULTS: Compared with the normal controls, apical
      rotation was markedly decreased in ApHCM patients (p<0.001), but the decreases in
      basal rotation were not significant. As a consequence, LV twist was significantly
      lower in ApHCM patients (p = 0.007). Apical radial (p = 0.01) and biplanar
      (p<0.001) strains in ApHCM were also significantly decreased. Compared to normal
      controls, LV twist-volume and twist-radial displacement curves clearly showed a
      decrement in the slope of the linear systolic phase and a loss of an inflection
      point separating the early from late untwisting phase in ApHCM patients.
      CONCLUSION: LV twist in ApHCM was significantly decreased due to a reduction in
      apical rotation, suggesting that regional myocardial changes in ApHCM can modify
      the global LV twist mechanics. Given the close interconnection between LV
      systolic and diastolic function, impairment of LV twist may lead to the loss of
      early diastolic suction and finally generate diastolic dysfunction in ApHCM.

PMID- 19858138
TI  - Longitudinal myocardial shortening in aortic stenosis: ready for prime time after
      30 years of research?

PMID- 19858140
TI  - Assessment of vascular function: flow-mediated constriction complements the
      information of flow-mediated dilatation.
AB  - OBJECTIVE: To determine whether vascular function assessed by low-flow-mediated
      constriction (L-FMC), a novel non-invasive method, complements the information
      obtained with "traditional" flow-mediated dilatation (FMD). DESIGN AND PATIENTS:
      In protocol 1, 12 healthy young volunteers underwent FMD and L-FMC measurements
      at rest and immediately after isometric exercise of the same hand. In protocol 2,
      24 patients with coronary artery disease, 24 with congestive heart failure, 24
      hypertensive patients and 64 healthy volunteers were enrolled to undergo L-FMC
      and FMD measurements. RESULTS: In protocol 1, exercise was associated with mean
      (SD) increases in radial artery blood flow, diameter and L-FMC (from -5.1 (1.5)%
      to -7.8 (3.4)%, p<0.05), while FMD was significantly blunted (from 6.0 (2.4)% to
      3.0 (3.2)%, p<0.05). In protocol 2, both FMD and L-FMC were blunted in the
      patient groups. Receiver operating curve analysis showed that, as compared with
      FMD alone, the combination of L-FMC and FMD significantly improved the
      sensitivity and specificity in detecting patients diagnosed with cardiovascular
      disease (p<0.05). CONCLUSION: In the first protocol, FMD and L-FMC were shown to
      be reciprocally regulated. A blunted FMD may, in certain cases, be an expression
      of increased resting vascular activation and not only of impaired endothelial
      function. In the second protocol, a statistical approach showed that
      implementation of L-FMC provides a better characterisation than FMD of vascular
      function in cardiovascular disease. Vascular (endothelial) function is a complex
      phenomenon which requires a multifaceted approach; it is suggested that a
      combination of L-FMC and FMD will provide additive and complementary information
      to "traditional" FMD measurements.

PMID- 19858139
TI  - Physical activity and physiological cardiac remodelling in a community setting:
      the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - OBJECTIVE: To evaluate the association of physical activity with left ventricular
      structure and function in the general population in a community setting. DESIGN:
      Cross-sectional study. SETTING: The Multi-Ethnic Study of Atherosclerosis (MESA),
      a population-based study of subclinical atherosclerosis. PARTICIPANTS: A
      multiethnic sample of 4992 participants (aged 45-84 years; 52% female) free of
      clinically apparent cardiovascular disease. INTERVENTIONS: Physical activity
      induces beneficial physiological cardiac remodelling in a cross-sectional study
      of non-athlete individuals. MAIN OUTCOME MEASURES: Left ventricular mass, volumes
      and function were assessed by cardiac magnetic resonance imaging. Physical
      activity, defined as intentional exercise and total moderate and vigorous
      physical activity, was assessed by a standard semiquantitative questionnaire.
      RESULTS: Left ventricular mass and end-diastolic volume were positively
      associated with physical activity (eg, 1.4 g/m(2) (women) and 3.1 g/m(2) (men)
      greater left ventricular mass in the highest category of intentional exercise
      compared with individuals reporting no intentional exercise; p = 0.05 and
      p<0.001, respectively). Relationships were non-linear, with stronger positive
      associations at lower levels of physical activity (test for non-linearity; p =
      0.02 and p = 0.03, respectively). Cardiac output and ejection fraction were
      unchanged with increased physical activity levels. Resting heart rate was lower
      in women and men with higher physical activity levels (eg, -2.6 beats/minute
      lower resting heart rate in the highest category of intentional exercise compared
      with individuals reporting no intentional exercise; p<0.001). CONCLUSIONS: In a
      community-based population free of clinically apparent cardiovascular disease,
      higher physical activity levels were associated with proportionally greater left
      ventricular mass and end-diastolic volume and lower resting heart rate.

PMID- 19858141
TI  - Left ventricular hypertrophy: reduction of blood pressure already in the normal
      range further regresses left ventricular mass.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) confers high cardiovascular risk.
      Regression of LVH reduces risk. Patients with blood pressure in the normal range
      and LVH are common. We investigated whether further reduction in blood pressure
      would further regress LVH. METHODS: 51 subjects with blood pressure in the normal
      range and echocardiographic left ventricular hypertrophy were randomly assigned
      to active treatment (antihypertensive medication) or placebo in a ratio of 2:1.
      The aim was to maintain office systolic blood pressure at 10 mm Hg less than
      baseline in the active arm and at baseline level in the placebo arm. Cardiac
      magnetic resonance imaging was used to measure change in left ventricular mass
      index over 12 months. RESULTS: 35 subjects completed the study (active 23:
      placebo 12). Average mean baseline office systolic blood pressure was 122 (SD 9)
      mm Hg in the active group and 124 (9) mm Hg in the placebo group (p = 0.646). The
      mean baseline left ventricular mass index was 65.88 (11.87) g/m(2) in the active
      group and 59.16 (11.13) g/m(2) in the placebo group (p = 0.114). The mean
      difference between baseline and end of study office systolic blood pressure was 
      9.33 (8.56) mm Hg in the active group and -0.08 (9.27) mm Hg in the placebo group
      (p = 0.007). The mean change in left ventricular mass index was -4.68 (7.31)
      g/m(2) in the active group and +1.97 (6.68) g/m(2) in the placebo group (p =
      0.014). CONCLUSIONS: Reduction in office systolic blood pressure, already in the
      normal range, of approximately 9 mm Hg, leads to a reduction in left ventricular
      mass. Further work is required to see if this also leads to a reduction in
      cardiovascular events. TRIAL REGISTRATION NUMBER: ISRCTN48331653.

PMID- 19858142
TI  - Evidence of an emerging digital divide among hospitals that care for the poor.
AB  - Some hospitals that disproportionately care for poor patients are falling behind
      in adopting electronic health records (EHRs). Data from a national survey
      indicate early evidence of an emerging digital divide: U.S. hospitals that
      provide care to large numbers of poor patients also had minimal use of EHRs.
      These same hospitals lagged others in quality performance as well, but those with
      EHR systems seemed to have eliminated the quality gap. These findings suggest
      that adopting EHRs should be a major policy goal of health reform measures
      targeting hospitals that serve large populations of poor patients.

PMID- 19858143
TI  - Remodelling acquired chest wall deformity after removal of a large axillary
      lipoma.
AB  - Acquired chest wall deformities are rarely encountered. Most of them result from
      pathologic process within the thorax, chest wall disease, iatrogenic deformities
      or post-traumatic. We present a case of a huge axillary mass deforming the chest
      wall. Surgery treated a well-encapsulated lipoma. Six months postoperatively, the
      chest wall restored to normal shape with active respiratory physiotherapy. This
      is the first reported case of spontaneous 'remodelling' of the chest wall without
      surgery.

PMID- 19858144
TI  - Comparison of detection of F-18 fluorodeoxyglucose positron emission tomography
      and 99mTc-hexamethylpropylene amine oxime labelled leukocyte scintigraphy for an
      aortic graft infection.
AB  - To compare F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG-PET)
      and (99m)Tc-hexamethylpropylene amine oxime ((99m)TC-HMPAO) labelled leukocyte
      scintigraphy for the diagnosis of vascular graft infection. A thoraco-abdominal
      CT-angiography and a (99m)TC-HMPAO labelled leukocyte scintigraphy did not show
      any graft infection in this case report whereas an F-18 FDG-PET showed a
      metabolic uptake around and all along the vascular graft. Further comparison
      between these two explorations is needed since the two techniques have not been
      compared in vascular graft infection.

PMID- 19858145
TI  - Plasmacytoid lymphoma within a left atrial myxoma: a rare coincidental dual
      pathology.
AB  - Primary malignant cardiac neoplasms are extremely rare. The occurrence of a
      malignant lymphoid tumour within a left atrial myxoma is highly atypical, with
      only one such case previously reported. Here, we describe a patient who presented
      with symptoms and signs of a left atrial myxoma. Subsequent specimen histology
      demonstrated the presence of lymphoma within the myxoma. We discuss the
      importance of histological diagnosis in order to best direct treatment and
      prognosis of such cases.

PMID- 19858146
TI  - Interinstitutional variation in prediction of death by SNAP-II and SNAPPE-II
      among extremely preterm infants.
AB  - BACKGROUND: Illness severity scores predict death among infants admitted to
      NICUs. We know of no study limited to a population defined by an extremely low
      gestational age. METHODS: A total of 1467 infants born before the 28th
      postmenstrual week at 14 institutions were given Score for Neonatal Acute
      Physiology II (SNAP-II) and Score for Neonatal Acute Physiology Perinatal
      Extension II (SNAPPE-II) values based on data collected within the first 12
      postnatal hours. All deaths in the intensive care nursery were identified.
      RESULTS: The rate of death before postnatal day 28 was 13% (interinstitutional
      range: 7%-20%), whereas the overall mortality rate was 18% (8%-31%). SNAP-II
      values, SNAPPE-II values, and mortality rates tended to decrease with increasing
      gestational age. Even within gestational age strata, however, the risk of death
      decreased with decreasing SNAP-II and SNAPPE-II values. The positive predictive
      values of most SNAP-II and SNAPPE-II cutoff levels were close to 30%. In general,
      institutions' mortality rates increased with the proportions of infants whose
      SNAP-II values were >/=30. CONCLUSION: The physiologic instability in the first
      12 postnatal hours that is identified by illness severity scores conveys
      information about the risk of death among infants at the lowest gestational ages.

PMID- 19858147
TI  - Hyponatremia in preterm neonates: not a benign condition.

PMID- 19858148
TI  - Prenatal corticosteroid prophylaxis for women delivering at late preterm
      gestation.
AB  - OBJECTIVE: We studied patterns of prenatal corticosteroid use, respiratory
      distress syndrome, and associated mortality rates to assess the congruence
      between knowledge and clinical practice related to such prophylaxis. METHODS: We
      used data on all live births in the United States (for the years 1989-1991, 1995
      1997, and 2002-2004) and Nova Scotia, Canada (for the years 1988-2007).
      Gestational age-specific temporal trends in infant deaths resulting from
      respiratory distress syndrome were quantified in the United States, and
      gestational age-specific temporal trends in corticosteroid use and morbidity
      (respiratory distress syndrome and intraventricular hemorrhage) were quantified
      in Nova Scotia. RESULTS: In the United States, infant deaths associated with
      respiratory distress syndrome decreased by 48% (95% confidence interval: 46%-50%)
      from 1989-1991 to 1995-1997 and then decreased by another 18% (95% confidence
      interval: 15%-22%) by 2002-2004. The latter mortality reduction was evident at 28
      to 32 weeks but not 33 to 36 weeks of gestation. Corticosteroid use at 28 to 32
      weeks was high in Nova Scotia and increased from 30.7% in 1988-1989 to 50.0% in
      1996-1997 and to 52.9% in 2006-2007, whereas rates of use at 33 to 36 weeks were
      much lower (eg, 6.7%, 17.0%, and 15.7% at 34 weeks in the 3 periods). Increased
      corticosteroid use at 33 and 34 weeks was estimated to reduce respiratory
      distress syndrome substantially. CONCLUSION: Addressing the knowledge-practice
      gap in corticosteroid use at 33 to 34 weeks should reduce infant morbidity and
      mortality rates.

PMID- 19858150
TI  - Using BMI to determine cardiovascular risk in childhood: how do the BMI cutoffs
      fare?
AB  - OBJECTIVE: Although adverse health outcomes are increased among children with BMI
      above the 85th (overweight) and 95th (obese) percentiles, previous studies have
      not clearly defined the BMI percentile at which adverse health outcomes begin to
      increase. We examined whether the existing BMI percentile cutoffs are optimal for
      defining increased risk for dyslipidemia, dysglycemia, and hypertension. METHODS:
      This was a cross-sectional analysis of the National Health and Nutrition
      Examination Survey from 2001 to 2006. Studied were 8216 children aged 6 to 17
      years, representative of the US population. BMI was calculated by using measured
      height and weight and converted to percentiles for age in months and gender.
      Outcome measures (dyslipidemia, dysglycemia, and hypertension) were based on
      laboratory and physical examination results; these were analyzed as both
      continuous and categorical outcomes. RESULTS: Significant increases for total
      cholesterol values and prevalence of abnormal cholesterol begin at the 80th
      percentile. Significant increases in glycohemoglobin values and prevalence of
      abnormal values begin at the 99th percentile. Consistent significant increases in
      the prevalence of high or borderline systolic blood pressure begin at the 90th
      percentile. CONCLUSIONS: Intervening for overweight children and their health
      requires clinical interventions that target the right children. On the basis of
      our data, a judicious approach to screening could include consideration of lipid
      screening for children beginning at the 80th percentile but for dysglycemia at
      the 99th percentile. Current definitions of overweight and obese may be more
      useful for general recognition of potential health problems and discussions with
      parents and children about the need to address childhood obesity.

PMID- 19858149
TI  - Complex multifactorial nature of significant hyperbilirubinemia in neonates.
AB  - OBJECTIVE: To determine whether glucose-6-phosphate dehydrogenase (G6PD), uridine
      diphosphoglucuronosyltransferase 1A1 (UGT1A1), and hepatic solute carrier organic
      anion transporter 1B1 (SLCO1B1) gene variants occur at greater frequency in
      neonates with significant hyperbilirubinemia. METHODS: Infants with gestational
      ages of >or=37 weeks and ages of <7 days were studied. Case subjects had >or=1
      bilirubin level above the 95th percentile (high-risk zone), whereas control
      subjects had bilirubin levels of <40th percentile (low-risk zone) at study entry.
      RESULTS: A total of 153 case subjects (median bilirubin level: 15.7 mg/dL) and
      299 control subjects (median bilirubin level: 4.6 mg/dL) were evaluated. There
      were no statistical differences in the frequencies of G6PD, UGT1A1, and SCLO1B1
      gene variants between case and control subjects (G6PD: 5.2% vs 3.3%; UGT1A1:
      14.4% vs 9.4%; SLCO1B1: 73.2% vs 73.6%). However, coexpression of the G6PD
      African A- mutation with UGT1A1 and/or SLCO1B1 variants was seen more frequently
      for case subjects. Case subjects more often demonstrated >or=2 factors
      contributing to hyperbilirubinemia, including ABO blood group heterospecificity
      in which the mother had blood group O (47.7% vs 11.4%), positive direct Coombs
      test results (33.3% vs 4%), sibling treated with phototherapy (16.3% vs 5.4%),
      maternal circulating blood group antibodies (10.5 vs 0.7%), maternal diabetes
      mellitus (13.1% vs 6.4%), and maternal East Asian ethnicity (6.5% vs 1.3%).
      CONCLUSIONS: Clinical contributors to hyperbilirubinemia were identified more
      frequently for case subjects but individually G6PD, UGT1A1, and SLCO1B1 variants
      were not. Coexpression of the G6PD African A- mutation with UGT1A1 and SLCO1B1
      variants was seen more often for case subjects.

PMID- 19858151
TI  - Neurobehavior in term, small-for-gestational age infants with normal placental
      function.
AB  - OBJECTIVE: The goal was to evaluate the neurobehavioral outcomes of term, small
      for-gestational age (SGA) newborns with normal placental function. METHODS: A
      cohort of consecutive term SGA newborns with normal prenatal umbilical artery
      Doppler ultrasound findings was created and compared with a group of term infants
      with size appropriate for gestational age, who were sampled from our general
      neonatal population. Neonatal behavior was evaluated at corrected age of 40 +/- 1
      weeks with the Neonatal Behavioral Assessment Scale. The effect of the study
      group on each Neonatal Behavioral Assessment Scale area was adjusted, through
      multivariate analysis of covariance, for smoking during pregnancy, maternal BMI,
      socioeconomic level, onset of labor, mode of delivery, use of epidural anesthetic
      medication, gestational age at delivery, postnatal age (in days) at evaluation,
      and gender. RESULTS: A total of 202 newborns (102 SGA and 100 appropriate for
      gestational age) were included. All of the neurobehavioral areas studied were
      poorer in the SGA group, with significance for attention, habituation, motor,
      social-interactive, and regulation of state. The average mean differences in
      scores between the study groups were 0.77 (95% confidence interval: 0.38-1. 14)
      for attention, 0.64 (95% confidence interval: 0.13-1.14) for habituation, 0.52
      (95% confidence interval: 0.31-0.74) for motor, 0.95 (95% confidence interval:
      0.54-1.37) for social-interactive, and 0.68 (95% confidence interval: 0.23-1.13)
      for regulation of state. These differences remained significant after adjustment
      for potential confounders. CONCLUSION: Term SGA newborns with no signs of
      placental insufficiency had poorer neurobehavioral competencies, which suggests
      delayed neurologic maturation.

PMID- 19858152
TI  - Structural correlates of preterm birth in the adolescent brain.
AB  - OBJECTIVE: The Stockholm Neonatal Project involves a prospective, cross
      sectional, population-based, cohort monitored for 12 to 17 years after birth; it
      was started with the aim of investigating the long-term structural correlates of
      preterm birth and comparing findings with reports on similar cohorts. METHODS:
      High-resolution anatomic and diffusion tensor imaging data measuring diffusion in
      30 directions were collected by using a 1.5-T MRI scanner. A total of 143
      adolescents (12.18-17.7 years of age) participated in the study, including 74
      formerly preterm infants with birth weights of <or=1500 g (range: 645-1486 g) and
      69 term control subjects. The 2 groups were well matched with respect to
      demographic and socioeconomic data. The anatomic MRI data were used for
      calculation of total brain volumes and voxelwise comparison of gray matter (GM)
      volumes. The diffusion tensor imaging data were used for voxelwise comparison of
      white matter (WM) microstructural integrity. RESULTS: The formerly preterm
      individuals possessed 8.8% smaller GM volume and 9.4% smaller WM volume. The GM
      and WM volumes of individuals depended on gestational age and birth weight. The
      reduction in GM could be attributed bilaterally to the temporal lobes, central,
      prefrontal, orbitofrontal, and parietal cortices, caudate nuclei, hippocampi, and
      thalami. Lower fractional anisotropy was observed in the posterior corpus
      callosum, fornix, and external capsules. CONCLUSIONS: Although preterm birth was
      found to be a risk factor regarding long-term structural brain development, the
      outcome was milder than in previous reports. This may be attributable to
      differences in social structure and neonatal care practices.

PMID- 19858153
TI  - The effect of weekend and holiday sleep compensation on childhood overweight and
      obesity.
AB  - OBJECTIVES: A growing trend in childhood sleep habits is to compensate for the
      weekday sleep deficit by longer weekend and holiday sleep duration. We aimed to
      investigate the effect of weekend/holiday sleep compensation in relation to
      childhood overweight and obesity. METHODS: This is a community-based cross
      sectional study with 5159 children (49.6% boys), mean age of 9.25 years (SD:
      1.78), from 13 primary schools in Hong Kong. Data on sleep patterns, lifestyle,
      body weight, and height of children were obtained from questionnaires. Sleep
      durations during weekdays, weekends, and holidays were predictor variables. BMI z
      scores and obesity/overweight status were the outcome measures. RESULTS: Children
      slept significantly longer during holidays (mean [SD]: 10.20 (0.92) hours) and
      weekends (school terms) (10.07 [0.93] hours) than during school weekdays (9.18
      [0.95] hours). Children with shorter sleep duration had higher BMI z scores
      regardless of the sleep parameters used in the analysis. Among children who slept
      <8 hours during weekdays, those children who did not compensate for their sleep
      deficit during weekends or holidays had significantly increased risk of
      overweight/obesity compared with those children with sleep compensation (odds
      ratios: 2.59 [95% confidence interval: 1.22-5.48] and 2.32 [95% confidence
      interval: 1.00-5.53], respectively). CONCLUSIONS: There was a prominent
      difference in sleep duration between weekdays and weekends/holidays among school
      children. Short sleep duration was associated with higher BMI, but compensation
      of sleep during weekends/holidays may partly ameliorate the risk of childhood
      overweight/obesity. Further prospective and interventional study is needed to
      delineate the risk-benefit effect of these increasingly common sleep habits among
      children and adolescents.

PMID- 19858154
TI  - Disability among internationally adopted children in the United States.
AB  - OBJECTIVES: The objective of this study was to estimate disability rates for
      internationally adopted children in the United States. METHODS: We conducted an
      analysis of restricted-access data from the complete long form of Census 2000 for
      internationally adopted children aged 5 to 15 in 2000, estimating disability
      rates by country of origin, controlling for gender, age at adoption, current age,
      and parental characteristics. RESULTS: Internationally adopted children have
      disability rates similar to those adopted domestically (11.7% vs 12.2%,
      respectively) and more than twice the rate for all children in that age range
      (5.8%). The adjusted odds of disability relative to domestic adoptees range from
      one half or less (China and Korea) to twice as large or more (Romania, Bulgaria,
      other Eastern Europe, and other Western Europe). CONCLUSIONS: The population of
      internationally adopted children is relatively small and diverse, posing
      challenges for researchers who hope to reach generalizable conclusions.
      Nevertheless, health, education, and social service professionals, as well as
      adoptive and prospective adoptive parents, should be aware of the risk for
      disabilities among internationally adopted children to devote the resources
      necessary to addressing them.

PMID- 19858155
TI  - A pilot trial of pramlintide home usage in adolescents with type 1 diabetes.
AB  - OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of
      home pramlintide use in adolescents with type 1 diabetes. PATIENTS AND METHODS:
      This was a randomized, 28-day pilot trial of pramlintide (maximum dose: 30 microg
      per meal) in 10 adolescents aged 13 to 17 years. End points included changes in
      hemoglobin A1c (HbA1c) values, body weight, and postprandial peak blood glucose
      levels and area under the curve on continuous glucose monitoring. RESULTS:
      Changes in HbA1c values, body weight, and total insulin dose declined in the
      treatment group compared with the control group (bootstrapped, P <or= .02 for
      each). The treatment group also demonstrated lower average dinner area under the
      curve (P = .02) and lower maximum breakfast (P = .03) and dinner (P = .02)
      postprandial blood glucose values. CONCLUSIONS: Pramlintide can help some
      adolescents to decrease postprandial hyperglycemia, HbA1c values, body weight,
      and insulin dosages. Additional large-scale trials should now be considered.

PMID- 19858156
TI  - Aluminum exposure from parenteral nutrition in preterm infants: bone health at 15
      year follow-up.
AB  - OBJECTIVE: Aluminum has known neurotoxicity and may impair short-term bone
      health. In a randomized trial, we showed reduced neurodevelopmental scores in
      preterm infants who were previously exposed to aluminum from parenteral nutrition
      solutions. Here, in the same cohort, we test the hypothesis that neonatal
      aluminum exposure also adversely affects long-term bone health, as indicated by
      reduced bone mass. METHODS: Bone area (BA) and bone mineral content (BMC) of
      lumbar spine, hip, and whole body were measured with dual radiograph
      absorptiometry in 13- to 15-year-olds who were born preterm and randomly assigned
      standard or aluminum-depleted parenteral nutrition solutions during the neonatal
      period. RESULTS: Fifty-nine children (32% of survivors) were followed. Those who
      were randomly assigned to standard parenteral nutrition solution had lower lumbar
      spine BMC, apparently explained by a concomitant decrease in bone size. In
      nonrandomized analyses, children who were exposed to neonatal aluminum intakes
      above the median (55 microg/kg) had lower hip BMC (by 7.6% [95% confidence
      interval: 0.12-13.8]; P = 0.02), [corrected] independent of bone (or body) size.
      CONCLUSIONS: Neonates who are exposed to parenteral aluminum may have reduced
      lumbar spine and hip bone mass during adolescence, potential risk factors for
      later osteoporosis and hip fracture. These findings need confirmation in larger,
      more detailed studies. Nevertheless, given our previous finding of adverse
      developmental outcome in these individuals and the sizeable number of
      contemporary infants who undergo intensive neonatal care and are still exposed to
      aluminum via parenteral feeding solutions, the potential adverse long-term
      consequences of early aluminum exposure now deserve renewed attention.

PMID- 19858157
TI  - Consensus Statement on Diagnostic Criteria for PHACE Syndrome.
AB  - OBJECTIVES: A subgroup of patients with infantile hemangiomas have associated
      structural anomalies of the brain, cerebral vasculature, eyes, sternum, and/or
      aorta in the neurocutaneous disorder known as PHACE syndrome. The diagnosis has
      been broadly inclusive by using a case definition of a facial hemangioma plus
      >or=1 extracutaneous features, leading to numerous reports of potential
      associated disease features, many of uncertain significance. This consensus
      statement was thus developed to establish diagnostic criteria for PHACE syndrome.
      METHODS: A multidisciplinary group of specialists with expertise in PHACE
      syndrome drafted initial diagnostic criteria on the basis of review of published,
      peer-reviewed medical literature and clinical experience. The group then convened
      in both executive and general sessions during the PHACE Syndrome Research
      Conference held in November 2008 for discussion and used a consensus method. All
      conflicting recommendations were subsequently reconciled via electronic
      communication and teleconferencing. RESULTS: These criteria were stratified into
      2 categories: (1) PHACE syndrome or (2) possible PHACE syndrome. Major and minor
      criteria were determined for the following organ systems: cerebrovascular,
      structural brain, cardiovascular, ocular, and ventral/midline. Definite PHACE
      requires the presence of a characteristic segmental hemangioma or hemangioma >5
      cm on the face or scalp plus 1 major criterion or 2 minor criteria. Possible
      PHACE requires the presence of a hemangioma >5 cm on the face or scalp plus 1
      minor criterion. The group recognized that it may be possible to have PHACE
      syndrome with a hemangioma affecting the neck, chest, or arm only or no cutaneous
      hemangioma at all. In such cases, fulfillment of additional required criteria
      would also lead to a possible PHACE diagnosis. CONCLUSIONS: These criteria
      represent current knowledge and are expected to enhance future assessments of
      PHACE syndrome. It is understood that modifications are to be expected over time
      to incorporate new research findings.

PMID- 19858158
TI  - Promoting lifelong health for adolescents and young adults with special health
      care needs.

PMID- 19858159
TI  - Defining vitamin D deficiency in children: beyond 25-OH vitamin D serum
      concentrations.

PMID- 19858160
TI  - Clinical and serological predictors for the recurrence of atrial fibrillation
      after electrical cardioversion.
AB  - AIMS: Although electrical cardioversion (CV) is effective in restoring sinus
      rhythm in patients with atrial fibrillation (AF), AF frequently recurs in spite
      of antiarrhythmic medications. We investigated the predictors of failed CV and AF
      recurrence after successful CV. METHODS AND RESULTS: In 81 patients (M:F = 63:18,
      59.1 +/- 10.5 years old) with AF who underwent CV, clinical, image, and CV
      findings (energy requirement, immediate recurrence of AF < 15 min), and pre-CV
      serological markers were evaluated. RESULTS: (i) During 13.1 +/- 10.6 months of
      follow-up, 8.6% (7/81) showed failed CV, 59.26% (48/81) showed AF recurrence, and
      32.1% (26/81) remained in sinus rhythm (no recurrence). (ii) Failed CV showed
      higher plasma levels of transforming growth factor (TGF)-beta (P = 0.0260) than
      those with successful CV. (iii) Patients with AF recurrence were older (60.4 +/-
      9.0 years old vs. 55.3 +/- 12.5 years old, P = 0.0220), had a higher incidence of
      spontaneous echo contrast (SEC; 68.1 vs. 40.0%, P = 0.0106), a lower prescription
      rate of angiotensin-converting enzyme inhibitor (ACE-I)/angiotensin receptor
      blocker (ARB; 27.0 vs. 50.0%, P = 0.0248) or spironolactone (0.0 vs. 19.2%, P =
      0.0007), and lower plasma levels of stromal cell-derived factor (SDF)-1alpha (P =
      0.0105). CONCLUSION: Post-CV recurrence commonly occurs in patients with age >60
      years, SEC, under-utilization of ACE-I/ARB or spironolactone, and low plasma
      levels of SDF-1alpha. High plasma level of TGF-beta predicts failed CV.

PMID- 19858162
TI  - Characterisation and measurement of signals generated by DVB-H 'GAP-filler'
      repeaters.
AB  - DVB-H (Digital Video Broadcasting Handheld) is the standard developed by DVB
      Project and approved by ETSI with the aim of providing the reception of DVB
      signals even in mobility but also data transfers and multimedia services. The
      introduction and development of the DVB-H system is still ongoing. In this
      context, this work focuses on the temporal trend of electromagnetic impact of an
      urban DVB-H repeater (called 'gap-filler') for exposure assessment purposes; it
      also describes a method for its measurement by means of narrow band instrumental
      chains.

PMID- 19858161
TI  - Clinical efficacy of first- and second-line treatments for HIV-associated
      Pneumocystis jirovecii pneumonia: a tri-centre cohort study.
AB  - OBJECTIVES: First-line therapy for Pneumocystis jirovecii pneumonia (PCP) is
      trimethoprim/sulfamethoxazole. Few data exist to guide the choice of second-line
      therapy for patients failing or developing toxicity to first-line therapy.
      METHODS: A case note review of 1122 patients with 1188 episodes of HIV-associated
      PCP from three observational cohorts in Copenhagen, London and Milan, between
      1989 and 2004, was conducted. RESULTS: Trimethoprim/sulfamethoxazole (962 PCP
      episodes, 81%) was the most frequently used first-line therapy, followed by
      intravenous pentamidine (87 episodes, 7%), clindamycin/primaquine (72 episodes,
      6%) and 'other' (atovaquone, dapsone/pyrimethamine, trimetrexate or inhaled
      pentamidine; 67 episodes, 6%). Rates of unchanged therapy were
      trimethoprim/sulfamethoxazole = 79%, clindamycin/primaquine = 65% and pentamidine
      = 60% (P < 0.001). First-line therapy was changed because of failure in 82 (7%)
      episodes and because of toxicity in 198 (17%) episodes. Three month survival
      rates were trimethoprim/sulfamethoxazole = 85%, clindamycin/primaquine = 81% and
      pentamidine = 76% (P = 0.09). After adjustment for possible confounders,
      pentamidine was associated with a significantly greater risk of death at 3 months
      [hazard ratio (HR) = 2.0, 95% confidence interval (CI) = 1.2-3.4]. Second-line
      therapy survival rates differed: trimethoprim/sulfamethoxazole = 85%;
      clindamycin/primaquine = 87%; and pentamidine = 60% (P = 0.01). Multivariable
      time-updated Cox regression analysis showed a greater risk of death associated
      with pentamidine (HR = 3.3, 95% CI = 2.2-5.0), but not for
      clindamycin/primaquine, when both were compared with
      trimethoprim/sulfamethoxazole. CONCLUSIONS: Pentamidine was associated with a
      greater risk of death when used as first- and second-line therapy for HIV
      associated PCP, and was associated with more treatment changes.
      Clindamycin/primaquine appeared superior to pentamidine as second-line therapy
      for PCP in patients failing or developing toxicity with
      trimethoprim/sulfamethoxazole. In patients failing first-line treatment with non
      trimethoprim/sulfamethoxazole regimens, second-line therapy should be
      trimethoprim/sulfamethoxazole.

PMID- 19858163
TI  - Investigation of the role of tumour necrosis factor-{alpha}, interleukin-1{beta},
      interleukin-10, nitric oxide and rheumatoid factor-immunoglobulin M in a rat
      model of arthritis.
AB  - Collagen-induced arthritis (CIA) in rats is a widely used preclinical animal
      model of rheumatoid arthritis (RA). However, CIA development in Sprague-Dawley
      (SD) rats is less severe in terms of inflammatory response compared with other
      strains. Therefore, a modified CIA model called MCIA, using N-acetylmuramyl
      dipeptide (MDP), has been developed in the less sensitive SD rat strains. This
      work was conducted to better understand the immunopathological role and
      contributions of the pro-inflammatory T-helper type 1 (Th-1) cytokines and
      inflammatory mediators, interleukin-1 (IL-1beta), tumour necrosis factor-alpha
      (TNF-alpha) and nitric oxide (NO); the anti-inflammatory T-helper type 2 (Th-2)
      cytokine, IL-10 and autoantibodies such as rheumatoid factor (RF)-immunoglobulin
      M (IgM) in this newly developed RA model. TNF-alpha, NO and RF-IgM levels were
      significantly increased, while IL-1beta levels were not affected in this MCIA rat
      model. The levels of IL-10 were lower than the baseline when compared with
      controls. IN CONCLUSION: (1) the immunological features represented in the MCIA
      rat model favour the Th-1 cytokine profile over Th-2 and (2) RF-IgM can be used
      as a diagnostic test in preclinical RA models.

PMID- 19858164
TI  - Influence of preferred foodstuffs on the antinociceptive effects of orally
      administered buprenorphine in laboratory rats.
AB  - Oral administration of buprenorphine is becoming a popular method of providing
      analgesia for laboratory rodents. The mixing of buprenorphine with flavoured
      jello, which rodents find palatable, is becoming a commonly used method as it is
      thought to improve the efficacy of oral buprenorphine by increasing the time
      available for it to be absorbed via the oral mucosa. The aim of this study was to
      assess the effect of various methods of buprenorphine administration
      (subcutaneous saline, subcutaneous buprenorphine [0.05 mg/kg], buprenorphine
      gavage [0.5 mg/kg], buprenorphine in jello [0.5 mg/kg] and buprenorphine in
      golden syrup [0.5 mg/kg]) on thermal antinociceptive thresholds in laboratory
      rats. Buprenorphine administered subcutaneously, by gavage, in jello and in syrup
      induced significant increases in thermal antinociceptive thresholds compared with
      saline. This effect was observed up to 5 h postadministration for buprenorphine
      administered subcutaneously and by gavage, but only for one hour
      postadministration for buprenorphine administered in jello and in syrup.

PMID- 19858165
TI  - Accidental induced seizures in three cynomologus macaques following
      administration of ceftriaxone dissolved in 1% lidocaine diluent.
AB  - Following initial signs of dural infection, or as prophylactic postoperative
      therapy, three cynomologus macaques were given an intramuscular or a subcutaneous
      injection of ceftriaxone dissolved in a 1% lidocaine diluent (CL). Two to 15 min
      later, all three monkeys experienced a long-lasting generalized apnoeic clonic
      convulsive seizure. The injected doses of lidocaine (0.7-2 mg/kg) were as low as
      7-20-fold less than the experimental intravenous dosage (14.2 +/- 3.2 mg/kg)
      previously reported to induce seizure in healthy rhesus monkeys. Under different
      clinical conditions, the same three animals were either once (1 animal) or
      repeatedly given CL without any resultant neurological alterations. The monkeys
      had a cranial device implanted and two of them were craniotomized. This first
      report of accidental lidocaine-induced seizure in laboratory non-human primates
      following CL injection strongly suggests increased susceptibility when lidocaine
      administration is associated with central nervous system alteration. A novel
      hypothesis, the possible role of cytokine in lowering the lidocaine seizure
      threshold, is suggested.

PMID- 19858166
TI  - A preliminary investigation into the practicality of use and duration of action
      of slow-release preparations of morphine and hydromorphone in laboratory rats.
AB  - Significant advances have been made in our ability to assess pain and administer
      appropriate pain relief in laboratory animals. However, providing long-lasting
      analgesia using a route that does not involve animal restraint remains difficult.
      The objective of this study was to investigate whether oral administration of
      slow-release morphine or hydromorphone results in increased thermal nociception
      in laboratory rats. The results showed that 64 mg/kg morphine and 16 mg/kg
      hydromorphone induced comparable increases in foot withdrawal latencies for up to
      three hours postadministration; however, slow-release morphine increased response
      latencies for up to 11 hours. Whether these dose rates provide clinically
      effective pain relief has yet to be determined; however, these data suggest that
      using slow-release preparations could be an effective and highly practical method
      of elevating pain thresholds for a relatively prolonged period.

PMID- 19858167
TI  - Permanent catheterization of the carotid artery induces kidney infection and
      inflammation in the rat.
AB  - Catheterization of the carotid artery and the jugular vein is one of the most
      commonly applied techniques used to gain intravascular access in pharmacology
      studies on rodents. We catheterized 10 rats by conventional clean techniques, 10
      rats by aseptic techniques and 10 rats by conventional clean techniques using a
      heparin-coated catheter rather than an ordinary non-coated polyvinyl chloride
      catheter. In all groups, approximately 80% of the rats developed kidney infection
      and 10-30% of the rats were septicaemic. Clinical chemistry did not indicate
      severe kidney damage, but serum haptoglobin and body temperature rises indicated
      an inflammatory response in rats independent of the surgical method. Heparin
      coating did not seem to improve the usability of the catheter. It is concluded
      that this commonly used method for catheterization has an impact on animals that
      may very well render them unsuitable for the purpose, e.g. pharmacological
      research, and therefore an alternative method would be preferable.

PMID- 19858168
TI  - A novel water delivery system for administering volatile chemicals while
      minimizing chemical waste in rodent toxicity studies.
AB  - Rodent toxicity studies typically use water bottles to administer test chemicals
      via drinking water. However, water bottles provide inconsistent exposure of
      volatile chemicals due to varying headspace, and lead to excessive waste of test
      material. To refine drinking water toxicity studies in rodents by enhancing
      sample quality and consistency, and minimizing waste, we designed and implemented
      a novel water delivery system that keeps the water chilled, headspace free and
      protected from light. Materials used were resistant to chemical interaction. In
      this gravity-fed system, a 6-L Teflon water bag, stored in a polystyrene cooler
      on the cage rack, was connected to a stainless steel manifold delivering water to
      five cages via specialized drinking valves. Due to the absence of headspace in
      the water bag, this system allows consistent exposure of volatile chemicals. In
      addition, small diameter tubing throughout the system reduces the amount of test
      material residing in the system and minimizes chemical waste.

PMID- 19858169
TI  - Comparison of different aminoglycoside antibiotic treatments to refine
      ototoxicity studies in adult mice.
AB  - Hearing and balance receptors in the inner ear are highly susceptible to damage
      caused by a wide variety of toxic substances, including aminoglycosides. This
      class of antibiotics is commonly used in medicine, even though they may produce
      irreversible bilateral neurosensorial deafness. To identify potential ototoxic
      agents and novel therapeutic targets, it is necessary to generate standardized
      animal models of aminoglycoside ototoxicity, which will also serve to explore
      otic cell repair and regeneration. Although the mouse is the species most often
      used in biomedical research, due to the genetic information and genetically
      modified strains available, there are few standard models of aminoglycoside
      ototoxicity in adult mice. Most protocols to produce ototoxicity in adult mice
      employ high doses of aminoglycosides for long periods of time, which causes
      systemic toxicity, side-effects and high mortality rates. Here, we compare the
      effects of systemic treatment with four different, yet common, aminoglycoside
      antibiotics in two mouse strains, evaluating their effects on mortality, cochlear
      morphology and auditory brainstem responses. Our data indicate that gentamicin
      and neomycin caused high mortality in the adult mouse without significantly
      changing the auditory threshold. Amikacin produced a tolerable rate of mortality
      but at doses that did not exhibit ototoxicity. Finally, intramuscular injection
      of kanamycin in C57BL/6JOlaHsd mice induced significant dose-dependent bilateral
      hearing loss with a moderate rate of mortality and less discomfort than following
      subcutaneous administration.

PMID- 19858170
TI  - Kinetics of {alpha}2-macroglobulin and {alpha}1-acid glycoprotein in rats
      subjected to repeated acute inflammatory stimulation.
AB  - The kinetics of alpha(2)-macroglobulin (alpha2M) and alpha(1)-acid glycoprotein
      (AAG) in rats repeatedly stimulated with intramuscular injections of turpentine
      oil at doses 0.05 and 0.4 mL/rat were investigated. Mean serum levels of alpha2M
      peaked at 48 h after the first turpentine oil injection, reaching 1.74 and 2.36
      mg/mL at 0.05 and 0.4 mL/rat, respectively. AAG peaks were also observed at 48 h
      after injection, and the mean values were 2.02 and 2.53 mg/mL, respectively.
      These peak values of alpha2M and AAG differed significantly between the 0.05 and
      0.4 mL/rat injection groups. Mean serum levels of interleukin-6 (IL-6) at 0.05
      mL/rat were 52.61 pg/mL at 12 h, 48.86 pg/mL at 36 h and 81.93 pg/mL at 84 h
      after the first injection. Mean IL-6 serum levels at 0.4 mL/rat were 215.24 pg/mL
      at 12 h, 56.33 pg/mL at 36 h and 39.25 pg/mL at 84 h after the first injection.
      Mean serum levels of cytokine-induced chemoattractant-1 (CINC-1) at a dose of
      0.05 mL/rat were 5.70 ng/mL at 12 h, 5.58 ng/mL at 36 h and 4.58 ng/mL at 84 h
      after the first injection. Mean serum levels of CINC-1 after injection at 0.4
      mL/rat were 11.57 ng/mL at 12 h, 4.68 ng/mL at 36 h and 4.42 ng/mL at 84 h. Serum
      levels of IL-6 differed significantly at 12, 24, 72 and 84 h, while those of CINC
      1 differed significantly at 12, 24, 48 and 96 h between the 0.05 and 0.4 mL/rat
      injection groups. Differences in peak serum levels in the 0.05 and 0.4 mL/rat
      groups were attributed to differences in the production of IL-6 and CINC-1, which
      are thought to contribute to alpha2M and AAG production.

PMID- 19858171
TI  - HABA-based ionic liquid matrices for UV-MALDI-MS analysis of heparin and heparan
      sulfate oligosaccharides.
AB  - Polysulfated carbohydrates such as heparin (HP) and heparan sulfate (HS) are not
      easily amenable to usual ultraviolet matrix-assisted laser desorption/ionization
      mass spectrometry (UV-MALDI)-MS analysis due to the thermal lability of their O-
      and N-SO(3) moieties, and their poor ionization efficiency with common
      crystalline matrices. Recently, ionic liquid matrices showed considerable
      advantages over conventional matrices for MALDI-MS of acidic compounds. Two new
      ionic liquid matrices (ILMs) based on the combination of 2-(4
      hydroxyphenylazo)benzoic acid (HABA) with 1,1,3,3-tetramethylguanidine and
      spermine were evaluated in the study herein. Both ILMs were successfully applied
      to the analysis of synthetic heparin oligosaccharides of well-characterized
      structures as well as to heparan sulfate-derived oligosaccharides from enzymatic
      depolymerization. HABA-based ILMs showed improved signal-to-noise ratio as well
      as a decrease of fragmentation/desulfation processes and cation exchange.
      Sulfated oligosaccharides were detected with higher sensitivity than usual
      crystalline matrices, and their intact fully O- and N-sulfated species [M-Na](-)
      were easily observed on mass spectra. MALDI-MS characterization of challenging
      analytes such as heparin octasaccharide carrying 8-O and 4 N-sulfo groups, and
      heparin octadecasulfated dodecasaccharide was successfully achieved.

PMID- 19858172
TI  - Food incentives and completion of tuberculosis treatment.

PMID- 19858173
TI  - Cardiomyopathy.

PMID- 19858174
TI  - Food incentives to improve completion of tuberculosis treatment: randomised
      controlled trial in Dili, Timor-Leste.
AB  - OBJECTIVE: To determine the effectiveness of the provision of whole food to
      enhance completion of treatment for tuberculosis. DESIGN: Parallel group
      randomised controlled trial. SETTING: Three primary care clinics in Dili, Timor
      Leste. PARTICIPANTS: 270 adults aged >or=18 with previously untreated newly
      diagnosed pulmonary tuberculosis. MAIN OUTCOME MEASURES: Completion of treatment
      (including cure). Secondary outcomes included adherence to treatment, weight
      gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to
      allocation status. Interventions Participants started standard tuberculosis
      treatment and were randomly assigned to intervention (nutritious, culturally
      appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or
      control (nutritional advice, n=133) groups. Randomisation sequence was computer
      generated with allocation concealment by sequentially numbered, opaque, sealed
      envelopes. RESULTS: Most patients with tuberculosis were poor, malnourished men
      living close to the clinics; 265/270 (98%) contributed to the analysis. The
      intervention had no significant beneficial or harmful impact on the outcome of
      treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7)
      but did lead to improved weight gain at the end of treatment (10.1% v 7.5%
      improvement, P=0.04). Itch was more common in the intervention group (21% v 9%,
      P<0.01). In a subgroup analysis of patients with positive results on sputum
      smears, there were clinically important improvements in one month sputum
      clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3).
      CONCLUSION: Provision of food did not improve outcomes with tuberculosis
      treatment in these patients in Timor-Leste. Further studies in different settings
      and measuring different outcomes are required. TRIAL REGISTRATION: Clinical
      Trials NCT00192556.

PMID- 19858176
TI  - Children in deprived areas at most risk of road injuries.

PMID- 19858182
TI  - Cases of swine flu in England almost double in a week.

PMID- 19858184
TI  - Increased cAMP levels modulate transforming growth factor-beta/Smad-induced
      expression of extracellular matrix components and other key fibroblast effector
      functions.
AB  - cAMP is a key messenger of many hormones and neuropeptides, some of which
      modulate the composition of extracellular matrix. Treatment of human dermal
      fibroblasts with dibutyryl cyclic AMP and forskolin antagonized the inductive
      effects of transforming growth factor-beta (TGF-beta) on the expression of
      collagen, connective tissue growth factor, tissue inhibitor of matrix
      metalloproteinase-1, and plasminogen activator inhibitor type I, four
      prototypical TGF-beta-responsive genes. Increased intracellular cAMP prevented
      TGF-beta-induced Smad-specific gene transactivation, although TGF-beta-mediated
      Smad phosphorylation and nuclear translocation remained unaffected. However,
      increased cAMP levels abolished TGF-beta-induced interaction of Smad3 with its
      transcriptional co-activator cAMP-response element-binding protein (CREB)-binding
      protein (CBP)/p300. Overexpression of the transcriptional co-activator CBP/p300
      rescued Smad-specific gene transcription in the presence of cAMP suggesting that
      sequestration of limited amounts of CBP/p300 by the activated cAMP/CREB pathway
      is the molecular basis of this inhibitory effect. These findings were extended by
      two functional assays. Increased intracellular cAMP levels suppressed the
      inductive activity of TGF-beta to contract mechanically unloaded collagen
      lattices and resulted in an attenuation of fibroblast migration of mechanically
      induced cell layer wounds. Of note, cAMP and TGF-beta synergistically induced
      hyaluronan synthase 2 (HAS2) expression and hyaluronan secretion, presumably via
      putative CREB-binding sites adjacent to Smad-binding sites within the HAS2
      promoter. Our findings identify the cAMP pathway as a potent but differential and
      promoter-specific regulator of TGF-beta-mediated effects involved in
      extracellular matrix homeostasis.

PMID- 19858185
TI  - Revised role of glycosaminoglycans in TAT protein transduction domain-mediated
      cellular transduction.
AB  - Cellular uptake of the human immunodeficiency virus TAT protein transduction
      domain (PTD), or cell-penetrating peptide, has previously been surmised to occur
      in a manner dependent on the presence of heparan sulfate proteoglycans that are
      expressed ubiquitously on the cell surface. These acidic polysaccharides form a
      large pool of negative charge on the cell surface that TAT PTD binds avidly.
      Additionally, sulfated glycans have been proposed to aid in the interaction of
      TAT PTD and other arginine-rich PTDs with the cell membrane, perhaps aiding their
      translocation across the membrane. Surprisingly, however, TAT PTD-mediated
      induction of macropinocytosis and cellular transduction occurs in the absence of
      heparan sulfate and sialic acid. Using labeled TAT PTD peptides and fusion
      proteins, in addition to TAT PTD-Cre recombination-based phenotypic assays, we
      show that transduction occurs efficiently in mutant Chinese hamster ovary cell
      lines deficient in glycosaminoglycans and sialic acids. Similar results were
      obtained in cells where glycans were enzymatically removed. In contrast,
      enzymatic removal of proteins from the cell surface completely ablated TAT PTD
      mediated transduction. Our findings support the hypothesis that acidic glycans
      form a pool of charge that TAT PTD binds on the cell surface, but this binding is
      independent of the PTD-mediated transduction mechanism and the induction of
      macropinocytotic uptake by TAT PTD.

PMID- 19858186
TI  - Wnt/beta-catenin and retinoic acid receptor signaling pathways interact to
      regulate chondrocyte function and matrix turnover.
AB  - Activation of the Wnt/beta-catenin and retinoid signaling pathways is known to
      tilt cartilage matrix homeostasis toward catabolism. Here, we investigated
      possible interactions between these pathways. We found that all-trans-retinoic
      acid (RA) treatment of mouse epiphyseal chondrocytes in culture did increase
      Wnt/beta-catenin signaling in the absence or presence of exogenous Wnt3a, as
      revealed by lymphoid enhancer factor/T-cell factor/beta-catenin reporter activity
      and beta-catenin nuclear accumulation. This stimulation was accompanied by
      increased gene expression of Wnt proteins and receptors and was inhibited by co
      treatment with Dickkopf-related protein-1, an extracellular inhibitor of Wnt/beta
      catenin signaling, suggesting that RA modulates Wnt signaling at Wnt cell surface
      receptor level. RA also enhanced matrix loss triggered by Wnt/beta-catenin
      signaling, whereas treatment with a retinoid antagonist reduced it.
      Interestingly, overexpression of retinoic acid receptor gamma (RARgamma) strongly
      inhibited Wnt/beta-catenin signaling in retinoid-free cultures, whereas small
      interfering RNA-mediated silencing of endogenous RARgamma expression strongly
      increased it. Small interfering RNA-mediated silencing of RARalpha or RARbeta had
      minimal effects. Co-immunoprecipitation and two-hybrid assays indicated that
      RARgamma interacts with beta-catenin and induces dissociation of beta-catenin
      from lymphoid enhancer factor in retinoid-free cultures. The N-terminal domain
      (AF-1) of RARgamma but not the C-terminal domain (AF-2) was required for
      association with beta-catenin, whereas both AF-1 and AF-2 were necessary for
      inhibition of beta-catenin transcriptional activity. Taken together, our data
      indicate that the Wnt and retinoid signaling pathways do interact in
      chondrocytes, and their cross-talks and cross-regulation play important roles in
      the regulation of cartilage matrix homeostasis.

PMID- 19858187
TI  - A cell-penetrating peptide derived from human lactoferrin with conformation
      dependent uptake efficiency.
AB  - The molecular events that contribute to the cellular uptake of cell-penetrating
      peptides (CPP) are still a matter of intense research. Here, we report on the
      identification and characterization of a 22-amino acid CPP derived from the human
      milk protein, lactoferrin. The peptide exhibits a conformation-dependent uptake
      efficiency that is correlated with efficient binding to heparan sulfate and lipid
      induced conformational changes. The peptide contains a disulfide bridge formed by
      terminal cysteine residues. At concentrations exceeding 10 mum, this peptide
      undergoes the same rapid entry into the cytoplasm that was described previously
      for the arginine-rich CPPs nona-arginine and Tat. Cytoplasmic entry strictly
      depends on the presence of the disulfide bridge. To better understand this
      conformation dependence, NMR spectroscopy was performed for the free peptide, and
      CD measurements were performed for free and lipid-bound peptide. In solution, the
      peptides showed only slight differences in secondary structure, with a
      predominantly disordered structure both in the presence and absence of the
      disulfide bridge. In contrast, in complex with large unilamellar vesicles, the
      conformation of the oxidized and reduced forms of the peptide clearly differed.
      Moreover, surface plasmon resonance experiments showed that the oxidized form
      binds to heparan sulfate with a considerably higher affinity than the reduced
      form. Consistently, membrane binding and cellular uptake of the peptide were
      reduced when heparan sulfate chains were removed.

PMID- 19858188
TI  - Subunit organization and reversal-associated movements in the flagellar switch of
      Escherichia coli.
AB  - Bacterial flagella contain a rotor-mounted protein complex termed the switch
      complex that functions in flagellar assembly, rotation, and
      clockwise/counterclockwise direction control. In Escherichia coli and Salmonella,
      the switch complex contains the proteins FliG, FliM, and FliN and corresponds
      structurally with the C-ring in the flagellar basal body. Certain features of
      subunit organization in the switch complex have been deduced previously, but
      details of subunit organization in the lower part of the C-ring and the molecular
      movements responsible for motor switching remain unclear. In this study, we use
      cross-linking, binding, and mutational experiments to examine subunit
      organization in the bottom of the C-ring and to probe movements that occur upon
      switching. The results show that FliN tetramers alternate with FliM C-terminal
      domains to form the bottom of the C-ring in an arrangement that closely
      reproduces the major features observed in electron microscopic reconstructions.
      When motors were switched to clockwise rotation by a repellent stimulus, cross
      link yields were altered in a pattern indicating relative movement of FliN and
      FliM(C). These results are discussed in the framework of a structurally grounded
      hypothesis for the switching mechanism.

PMID- 19858189
TI  - Kinetic mechanism for the binding of eIF4F and tobacco Etch virus internal
      ribosome entry site rna: effects of eIF4B and poly(A)-binding protein.
AB  - The wheat germ eukaryotic translation initiation factor (eIF) 4F binds tightly to
      the mRNA internal ribosome entry site (IRES) of tobacco etch virus (TEV) to
      promote translation initiation. When eIF4F is limiting, TEV is preferentially
      translated compared with host cell mRNA. To gain insight into the dynamic process
      of protein synthesis initiation and the mechanism of binding, the kinetics of
      eIF4F binding to TEV IRES were examined. The association rate constant (k(on))
      and dissociation rate constant (k(off)) for eIF4F binding to IRES were 59 +/- 2.1
      micro s(-1) and 12.9 +/- 0.3 s(-1), respectively, comparable with the rates for
      capped RNA. Binding of eIF4E or eIF4F to the cap of mRNA is the rate-limiting
      step for initiation of cap-dependent protein synthesis. The concentration
      dependence of the reactions suggested a simple one-step association mechanism.
      However, the association rate was reduced more than 10-fold when KCl
      concentration was increased from 50 to 300 mm, whereas the dissociation rate
      constant was increased 2-fold. The addition of eIF4B and poly(A)-binding protein
      enhanced the association rate of eIF4F approximately 3-fold. These results
      suggest a mechanism where eIF4F initially binds electrostatically, followed by a
      conformational change to further stabilize binding. Poly(A)-binding protein and
      eIF4B mainly affect the eIF4F/TEV association rate. These results demonstrate the
      first direct kinetic measurements of translation initiation factor binding to an
      IRES.

PMID- 19858190
TI  - Conformational changes associated with proton-dependent gating of ASIC1a.
AB  - Acid-sensing ion channels are proton-gated Na(+) channels expressed predominantly
      in neurons. How channel structure translates an environmental stimulus into
      changes in pore permeability remains largely undefined. The pore of ASIC1 is
      defined by residues in the second transmembrane domain (TM2), although a segment
      of the outer vestibule is formed by residues of TM1. We used the voltage clamp
      fluorometry technique to define the role of the region preceding TM2 (pre-TM2) in
      activation and desensitization of mouse ASIC1a. Oocytes expressing E425C channels
      labeled with Alexa Fluor 488 C5-maleimide showed a change in the emission of the
      fluorescent probe in response to extracellular acidification. The time course of
      the change in fluorescence correlated with activation but not desensitization of
      E425C channels. The fluorescence emission did not change following extracellular
      acidification in oocytes carrying an inactivating mutation (W287G/E425C),
      although these channels were labeled and expressed at the plasma membrane. Our
      data indicate that pore opening occurs in conjunction with a conformational
      rearrangement of the pre-TM2. We observed a change in the emission of the
      fluorescent probe when labeled E425C channels transition from the desensitized to
      the resting state. The substituted-cysteine-accessibility method was used to
      determine whether the pre-TM2 has different conformations in the resting and
      desensitized states. State-dependent changes in accessibility to 2
      [(trimethylammonium)ethyl]methanethiosulfonate bromide modification were observed
      in oocytes expressing K421C, K422C, Y424C, and E425C channels. Our results
      suggest that the pre-TM2 of ASIC1a undergoes dynamic conformational
      rearrangements during proton-dependent gating.

PMID- 19858191
TI  - Probing nuclear localization signal-importin alpha binding equilibria in living
      cells.
AB  - The regulated process of protein import into the nucleus of a eukaryotic cell is
      mediated by specific nuclear localization signals (NLSs) that are recognized by
      protein-import receptors. In this study, we present fluorescence-based methods to
      quantitatively address the physicochemical details of NLS recognition by the
      receptor protein importin alpha (Impalpha) in living cells. First, by combining
      fluorescence recovery after photobleaching measurements and protein-concentration
      calibration, we quantitatively define nuclear import saturability and afford an
      affinity value for NLS-Impalpha binding. Second, by fluorescence lifetime imaging
      microscopy, we directly monitor the occurrence of NLS-Impalpha interaction and
      measure its effective dissociation constant (K(D)) in the actual cellular
      environment. Our kinetic and thermodynamic analyses independently indicate that
      the subsaturation of Impalpha with the expressed NLS cargo regulates nuclear
      import rates in living cells, in contrast to what can be predicted on the basis
      of available in vitro data. Finally, our experiments also provide evidence for
      the regulation of nuclear import mediated by the intrasteric importin beta
      binding domain of Impalpha and yield the first estimate of its autoinhibition
      energy in living cells.

PMID- 19858192
TI  - Cathepsin B-mediated autophagy flux facilitates the anthrax toxin receptor 2
      mediated delivery of anthrax lethal factor into the cytoplasm.
AB  - Anthrax lethal toxin (LeTx) is a virulence factor secreted by Bacillus anthracis
      and has direct cytotoxic effects on most cells once released into the cytoplasm.
      The cytoplasmic delivery of the proteolytically active component of LeTx, lethal
      factor (LF), is carried out by the transporter component, protective antigen,
      which interacts with either of two known surface receptors known as anthrax toxin
      receptor (ANTXR) 1 and 2. We found that the cytoplasmic delivery of LF by ANTXR2
      was mediated by cathepsin B (CTSB) and required lysosomal fusion with LeTx
      containing endosomes. Also, binding of protective antigen to ANXTR1 or -2
      triggered autophagy, which facilitated the cytoplasmic delivery of ANTXR2
      associated LF. We found that whereas cells treated with the membrane-permeable
      CTSB inhibitor CA074-Me- or CTSB-deficient cells had no defect in fusion of LC3
      containing autophagic vacuoles with lysosomes, autophagic flux was significantly
      delayed. These results suggested that the ANTXR2-mediated cytoplasmic delivery of
      LF was enhanced by CTSB-dependent autophagic flux.

PMID- 19858193
TI  - Regulated cleavage of prothrombin by prothrombinase: repositioning a cleavage
      site reveals the unique kinetic behavior of the action of prothrombinase on its
      compound substrate.
AB  - Prothrombinase converts prothrombin to thrombin via cleavage at Arg(320) followed
      by cleavage at Arg(271). Exosite-dependent binding of prothrombin to
      prothrombinase facilitates active site docking by Arg(320) and initial cleavage
      at this site. Precise positioning of the Arg(320) site for cleavage is implied by
      essentially normal cleavage at Arg(320) in recombinant prothrombin variants
      bearing additional Arg side chains either one or two residues away. However,
      mutation of Arg(320) to Gln reveals that prothrombinase can cleave prothrombin
      following Arg side chains shifted by as many as two residues N-terminal to the
      320 position at near normal rates. Further repositioning leads to a loss in
      cleavage at this region with an abrupt shift toward slow cleavage at Arg(271). In
      contrast, the binding constant for the active site docking step is strongly
      dependent on the sequence preceding the scissile bond as well as position. Large
      effects on binding only yield minor changes in rate until the binding constant
      passes a threshold value. This behavior is expected for a substrate that can
      engage the enzyme through mutually exclusive active site docking reactions
      followed by cleavage to yield different products. Cleavage site specificity as
      well as the ordered action of prothrombinase on its compound substrate is
      regulated by the thermodynamics of active site engagement of the individual sites
      as well as competition between alternate cleavage sites for active site docking.

PMID- 19858195
TI  - Molecular basis for galactosylation of core fucose residues in invertebrates:
      identification of caenorhabditis elegans N-glycan core alpha1,6-fucoside beta1,4
      galactosyltransferase GALT-1 as a member of a novel glycosyltransferase family.
AB  - Galectin CGL2 from the ink cap mushroom Coprinopsis cinerea displays toxicity
      toward the model nematode Caenorhabditis elegans. A mutation in a putative
      glycosyltransferase-encoding gene resulted in a CGL2-resistant C. elegans strain
      characterized by N-glycans lacking the beta1,4-galactoside linked to the alpha1,6
      linked core fucose. Expression of the corresponding GALT-1 protein in insect
      cells was used to demonstrate a manganese-dependent galactosyltransferase
      activity. In vitro, the GALT-1 enzyme showed strong selectivity for acceptors
      with alpha1,6-linked N-glycan core fucosides and required Golgi- dependent
      modifications on the oligosaccharide antennae for optimal synthesis of the Gal
      beta1,4-fucose structure. Phylogenetic analysis of the GALT-1 protein sequence
      identified a novel glycosyltransferase family (GT92) with members widespread
      among eukarya but absent in mammals.

PMID- 19858194
TI  - Chronic reduction of the cytosolic or mitochondrial NAD(P)-malic enzyme does not
      affect insulin secretion in a rat insulinoma cell line.
AB  - The cytosolic malic enzyme (ME1) has been suggested to augment insulin secretion
      via the malate-pyruvate and/or citrate-pyruvate shuttles, through the production
      of NADPH or other metabolites. We used selectable vectors expressing short
      hairpin RNA (shRNA) to stably decrease Me1 mRNA levels by 80-86% and ME1 enzyme
      activity by 78-86% with either of two shRNAs in the INS-1 832/13 insulinoma cell
      line. Contrary to published short term ME1 knockdown experiments, our long term
      targeted cells showed normal insulin secretion in response to glucose or to
      glutamine plus 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid. We found no
      increase in the mRNAs and enzyme activities of the cytosolic isocitrate
      dehydrogenase or glucose-6-phosphate dehydrogenase, which also produce cytosolic
      NADPH. There was no compensatory induction of the mRNAs for the mitochondrial
      malic enzymes Me2 or Me3. Interferon pathway genes induced in preliminary small
      interfering RNA experiments were not induced in the long term shRNA experiments.
      We repeated our study with an improved vector containing Tol2 transposition
      sequences to produce a higher rate of stable transferents and shortened time to
      testing, but this did not alter the results. We similarly used stably expressed
      shRNA to reduce mitochondrial NAD(P)-malic enzyme (Me2) mRNA by up to 95%, with
      severely decreased ME2 protein and a 90% decrease in enzyme activity. Insulin
      release to glucose or glutamine plus 2-aminobicyclo[2,2,1]heptane-2-carboxylic
      acid remained normal. The maintenance of robust insulin secretion after lowering
      expression of either one of these malic enzymes is consistent with the redundancy
      of pathways of pyruvate cycling and/or cytosolic NADPH production in insulinoma
      cells.

PMID- 19858196
TI  - Branched-chain amino acid metabolon: interaction of glutamate dehydrogenase with
      the mitochondrial branched-chain aminotransferase (BCATm).
AB  - The catabolic pathway for branched-chain amino acids includes deamination
      followed by oxidative decarboxylation of the deaminated product branched-chain
      alpha-keto acids, catalyzed by the mitochondrial branched-chain aminotransferase
      (BCATm) and branched-chain alpha-keto acid dehydrogenase enzyme complex (BCKDC).
      We found that BCATm binds to the E1 decarboxylase of BCKDC, forming a metabolon
      that allows channeling of branched-chain alpha-keto acids from BCATm to E1. The
      protein complex also contains glutamate dehydrogenase (GDH1), 4
      nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1,
      pyruvate carboxylase, and BCKDC kinase. GDH1 binds to the pyridoxamine 5'
      phosphate (PMP) form of BCATm (PMP-BCATm) but not to the pyridoxal 5'-phosphate
      BCATm and other metabolon proteins. Leucine activates GDH1, and oxidative
      deamination of glutamate is increased further by addition of PMP-BCATm.
      Isoleucine and valine are not allosteric activators of GDH1, but in the presence
      of 5'-phosphate-BCATm, they convert BCATm to PMP-BCATm, stimulating GDH1
      activity. Sensitivity to ADP activation of GDH1 was unaffected by PMP-BCATm;
      however, addition of a 3 or higher molar ratio of PMP-BCATm to GDH1 protected
      GDH1 from GTP inhibition by 50%. Kinetic results suggest that GDH1 facilitates
      regeneration of the form of BCATm that binds to E1 decarboxylase of the BCKDC,
      promotes metabolon formation, branched-chain amino acid oxidation, and cycling of
      nitrogen through glutamate.

PMID- 19858197
TI  - Pulsatile and sustained gonadotropin-releasing hormone (GnRH) receptor signaling:
      does the Ca2+/NFAT signaling pathway decode GnRH pulse frequency?
AB  - Gonadotropin-releasing hormone (GnRH) acts via 7 transmembrane region receptors
      on gonadotrophs to stimulate synthesis and secretion of the luteinizing hormone
      and follicle-stimulating hormone. It is secreted in pulses, and its effects
      depend on pulse frequency, but decoding mechanisms are unknown. Here we have used
      (nuclear factor of activated T-cells 2 (NFAT2)-emerald fluorescent protein) to
      monitor GnRH signaling. Increasing [Ca(2+)](i) causes calmodulin/calcineurin
      dependent nuclear NFAT translocation, a response involving proteins (calmodulins
      and NFATs) that decode frequency in other systems. Using live cell imaging,
      pulsatile GnRH caused dose- and frequency-dependent increases in nuclear NFAT2
      emerald fluorescent protein, and at low frequency, translocation simply tracked
      GnRH exposure (albeit with slower kinetics). At high frequency (30-min
      intervals), failure to return to basal conditions before repeat stimulation
      caused integrative tracking, illustrating how the relative dynamics of up- and
      downstream signals can increase efficiency of GnRH action. Mathematical modeling
      predicted desensitization of GnRH effects on [Ca(2+)](i) and that desensitization
      would increase with dose, frequency, and receptor number, but no such
      desensitization was seen in HeLa and/or LbetaT2 cells possibly because pulsatile
      GnRH did not reduce receptor expression (measured by immunofluorescence). GnRH
      also caused dose- and frequency-dependent activation of alphaGSU, luteinizing
      hormone beta, and follicle-stimulating hormone beta luciferase reporters, effects
      that were blocked by calcineurin inhibition. Pulsatile GnRH also activated an
      NFAT-responsive luciferase reporter, but this response was directly related to
      cumulative pulse duration. This together with the lack of desensitization of
      translocation responses suggests that NFAT may mediate GnRH action but is not a
      genuine decoder of GnRH pulse frequency.

PMID- 19858198
TI  - Ca2+/calmodulin-dependent protein kinase II binds to and phosphorylates a
      specific SAP97 splice variant to disrupt association with AKAP79/150 and modulate
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor
      (AMPAR) activity.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) promotes trafficking and
      activation of the GluR1 subunit of alpha-amino- 3-hydroxy-5-methyl-4
      isoxazolepropionic acid-type glutamate receptors (AMPARs) during synaptic
      plasticity. GluR1 is also modulated in parallel by multiprotein complexes
      coordinated by synapse-associated protein 97 (SAP97) that contain A-kinase
      anchoring protein 79/150 (AKAP79/150), protein kinase A, and protein phosphatase
      2B. Here we show that SAP97 is present in CaMKII immune complexes isolated from
      rodent brain as well as from HEK293 cells co-expressing CaMKIIalpha and SAP97.
      CaMKIIalpha phosphorylated recombinant SAP97 within immune complexes in vitro and
      in intact cells. Four alternative mRNA splice variants of SAP97 expressing
      combinations of four inserts (I2, I3, I4, I5) in the U5 region between Src
      homology 3 (SH3) and guanylyl kinase-like (GK) domains were identified in rat
      brain at postnatal day 21. CaMKIIalpha preferentially phosphorylated a full
      length SAP97 and a glutathione S-transferase (GST) fusion protein containing the
      I3 and I5 inserts (SAP97-I3I5 and GST-SH3-I3I5-GK, respectively) and also
      specifically interacted with GST-SH3-I3I5-GK compared with GST proteins
      containing other naturally occurring insert combinations. AKAP79/150 also
      directly and specifically bound only to GST-SH3-I3I5-GK, but CaMKII
      phosphorylation of GST-SH3-I3I5-GK prevented this interaction. AKAP79-dependent
      down-regulation of GluR1 AMPAR currents was ablated by overexpression of SAP97
      I2I5 (which does not bind AKAP79) or by infusion of active CaMKIIalpha.
      Collectively, the data suggest that CaMKIIalpha targets a specific SAP97 splice
      variant to disengage AKAP79/150 from regulating GluR1 AMPARs, providing new
      insight into protein-protein interactions and phosphorylation events that are
      required for normal regulation of glutamatergic synaptic transmission, learning,
      and memory.

PMID- 19858199
TI  - Alternative mechanism of activation of the epithelial na+ channel by cleavage.
AB  - We examined activation of the human epithelial sodium channel (ENaC) by cleavage.
      We focused on cleavage of alphaENaC using the serine protease subtilisin.
      Trimeric channels formed with alphaFM, a construct with point mutations in both
      furin cleavage sites (R178A/R204A), exhibited marked reduction in spontaneous
      cleavage and an approximately 10-fold decrease in amiloride-sensitive whole cell
      conductance as compared with alphaWT (2.2 versus 21.2 microsiemens (microS)).
      Both alphaWT and alphaFM were activated to similar levels by subtilisin cleavage.
      Channels formed with alphaFD, a construct that deleted the segment between the
      two furin sites (Delta175-204), exhibited an intermediate conductance of 13.2
      microS. More importantly, alphaFD retained the ability to be activated by
      subtilisin to 108.8 +/- 20.9 microS, a level not significantly different from
      that of subtilisin activated alphaWT (125.6 +/- 23.9). Therefore, removal of the
      tract between the two furin sites is not the main mechanism of channel
      activation. In these experiments the levels of the cleaved 22-kDa N-terminal
      fragment of alpha was low and did not match those of the C-terminal 65-kDa
      fragment. This indicated that cleavage may activate ENaC by the loss of the
      smaller fragment and the first transmembrane domain. This was confirmed in
      channels formed with alphaLD, a construct that extended the deleted sequence of
      alphaFD by 17 amino acids (Delta175-221). Channels with alphaLD were uncleaved,
      exhibited low baseline activity (4.1 microS), and were insensitive to subtilisin.
      Collectively, these data support an alternative hypothesis of ENaC activation by
      cleavage that may involve the loss of the first transmembrane domain from the
      channel complex.

PMID- 19858200
TI  - High speed atomic force microscopy visualizes processive movement of Trichoderma
      reesei cellobiohydrolase I on crystalline cellulose.
AB  - Fungal cellobiohydrolases act at liquid-solid interfaces. They have the ability
      to hydrolyze cellulose chains of a crystalline substrate because of their two
      domain structure, i.e. cellulose-binding domain and catalytic domain, and unique
      active site architecture. However, the details of the action of the two domains
      on crystalline cellulose are still unclear. Here, we present real time
      observations of Trichoderma reesei (Tr) cellobiohydrolase I (Cel7A) molecules
      sliding on crystalline cellulose, obtained with a high speed atomic force
      microscope. The average velocity of the sliding movement on crystalline cellulose
      was 3.5 nm/s, and interestingly, the catalytic domain without the cellulose
      binding domain moved with a velocity similar to that of the intact TrCel7A
      enzyme. However, no sliding of a catalytically inactive enzyme (mutant E212Q) or
      a variant lacking tryptophan at the entrance of the active site tunnel (mutant
      W40A) could be detected. This indicates that, besides the hydrolysis of
      glycosidic bonds, the loading of a cellulose chain into the active site tunnel is
      also essential for the enzyme movement.

PMID- 19858201
TI  - The lysine 48 and lysine 63 ubiquitin conjugates are processed differently by the
      26 s proteasome.
AB  - The role of Lys-63 ubiquitin chains in targeting proteins for proteasomal
      degradation is still obscure. We systematically compared proteasomal processing
      of Lys-63 ubiquitin chains with that of the canonical proteolytic signal, Lys-48
      ubiquitin chains. Quantitative mass spectrometric analysis of ubiquitin chains in
      HeLa cells determines that the levels of Lys-63 ubiquitin chains are insensitive
      to short-time proteasome inhibition. Also, the Lys-48/Lys-63 ratio in the 26 S
      proteasome-bound fraction is 1.7-fold more than that in the cell lysates, likely
      because some cellular Lys-63 ubiquitin conjugates are sequestered by Lys-63 chain
      specific binding proteins. In vitro, Lys-48 and Lys-63 ubiquitin chains bind the
      26 S proteasome comparably, whereas Lys-63 chains are deubiquitinated 6-fold
      faster than Lys-48 chains. Also, Lys-63 tetraubiquitin-conjugated UbcH10 is
      rapidly deubiquitinated into the monoubiquitinated form, whereas Lys-48
      tetraubiquitin targets UbcH10 for degradation. Furthermore, we found that both
      the ubiquitin aldehyde- and 1,10-phenanthroline-sensitive deubiquitinating
      activities of the 26 S proteasome contribute to Lys-48- and Lys-63-linkage
      deubiquitination, albeit the inhibitory extents are different. Together, our
      findings suggest that compared with Lys-48 chains, cellular Lys-63 chains have
      less proteasomal accessibility, and proteasome-bound Lys-63 chains are more
      rapidly deubiquitinated, which could cause inefficient degradation of Lys-63
      conjugates.

PMID- 19858203
TI  - Regulation of DAF-16-mediated Innate Immunity in Caenorhabditis elegans.
AB  - Activation of the innate immune system results in a rapid microbicidal response
      against microorganisms, which needs to be fine-tuned because uncontrolled immune
      responses can lead to infection and cancer, as well as conditions such as Crohn
      disease, atherosclerosis, and Alzheimer disease. Here we report that excessive
      activity of the conserved FOXO transcription factor DAF-16 enhances
      susceptibility to bacterial infections in Caenorhabditis elegans. We found that
      increased temperature activates not only DAF-16 nuclear import but also a control
      mechanism involved in DAF-16 nuclear export. The nuclear export of DAF-16
      requires heat shock transcription factor HSF-1 and Hsp70/HSP-1. Furthermore, we
      show that increased expression of the water channel Aquoporin-1 is responsible
      for the deleterious consequences of excessive DAF-16-mediated immune response.
      These studies reveal a stress-inducible mechanism involved in the regulation of
      DAF-16 and indicate that uncontrolled DAF-16 activity and water homeostasis are a
      cause of the deleterious effects of excessive immune responses.

PMID- 19858202
TI  - Cannabinoid receptor type 1- and 2-mediated increase in cyclic AMP inhibits T
      cell receptor-triggered signaling.
AB  - The aim of this study was to characterize inhibitory mechanisms on T cell
      receptor signaling mediated by the cannabinoid receptors CB1 and CB2. Both
      receptors are coupled to G(i/o) proteins, which are associated with inhibition of
      cyclic AMP formation. In human primary and Jurkat T lymphocytes, activation of
      CB1 by R(+)-methanandamide, CB2 by JWH015, and both by Delta9
      tetrahydrocannabinol induced a short decrease in cyclic AMP lasting less than 1
      h. However, this decrease was followed by a massive (up to 10-fold) and sustained
      (at least up to 48 h) increase in cyclic AMP. Mediated by the cyclic AMP
      activated protein kinase A and C-terminal Src kinase, the cannabinoids induced a
      stable phosphorylation of the inhibitory Tyr-505 of the leukocyte-specific
      protein tyrosine kinase (Lck). By thus arresting Lck in its inhibited form, the
      cannabinoids prevented the dephosphorylation of Lck at Tyr-505 in response to T
      cell receptor activation, which is necessary for the subsequent initiation of T
      cell receptor signaling. In this way the cannabinoids inhibited the T cell
      receptor-triggered signaling, i.e. the activation of the zeta-chain-associated
      protein kinase of 70 kDa, the linker for activation of T cells, MAPK, the
      induction of interleukin-2, and T cell proliferation. All of the effects of the
      cannabinoids were blocked by the CB1 and CB2 antagonists AM281 and AM630. These
      findings help to better understand the immunosuppressive effects of cannabinoids
      and explain the beneficial effects of these drugs in the treatment of T cell
      mediated autoimmune disorders like multiple sclerosis.

PMID- 19858204
TI  - TATA-binding Protein (TBP)-like Protein Is Engaged in Etoposide-induced Apoptosis
      through Transcriptional Activation of Human TAp63 Gene.
AB  - Accumulating evidence indicates that TBP (TATA-binding protein)-like protein
      (TLP) contributes to the regulation of stress-mediated cell cycle checkpoint and
      apoptotic pathways, although its physiological target genes have remained
      elusive. In the present study, we have demonstrated that human TAp63 is one of
      the direct transcriptional target genes of TLP. Enforced expression of TLP
      results in the transcriptional induction of the endogenous TAp63, but not of the
      other p53 family members such as TAp73 and p53. Consistent with these results,
      small interference RNA-mediated knockdown led to a significant down-regulation of
      the endogenous TAp63. Luciferase reporter assay and chromatin immunoprecipitation
      analysis revealed that the genomic region located at positions -487 to -29, where
      +1 represents the transcriptional initiation site of TAp63, is required for TLP
      dependent transcriptional activation of TAp63 and also TLP is efficiently
      recruited onto this region. Additionally, cells treated with anti-cancer drug
      etoposide underwent apoptosis in association with the transcriptional enhancement
      of TAp63 in a p53-independent manner, and the knockdown of the endogenous TLP
      reduced etoposide-induced apoptosis through repression of TAp63 expression. Taken
      together, our present study identifies a TLP-TAp63 pathway that is further
      implicated in stress-induced apoptosis.

PMID- 19858205
TI  - Generation and accumulation of immunosuppressive adenosine by human
      CD4+CD25highFOXP3+ regulatory T cells.
AB  - Naturally occurring regulatory T cells (nTreg) are crucial for maintaining
      tolerance to self and thus preventing autoimmune diseases and allograft
      rejections. In cancer, Treg down-regulate antitumor responses by several distinct
      mechanisms. This study analyzes the role the adenosinergic pathway plays in
      suppressive activities of human nTreg. Human CD4(+)CD25(high)FOXP3(+) Treg
      overexpress CD39 and CD73, ectonucleotidases sequentially converting ATP into AMP
      and adenosine, which then binds to A(2a) receptors on effector T cells,
      suppressing their functions. CD4(+)CD39(+) and CD4(+)CD25(high) T cells express
      low levels of adenosine deaminase (ADA), the enzyme responsible for adenosine
      breakdown, and of CD26, a surface-bound glycoprotein associated with ADA. In
      contrast, T effector cells are enriched in CD26/ADA but express low levels of
      CD39 and CD73. Inhibitors of ectonucleotidase activity (e.g. ARL67156) and
      antagonists of the A(2a) receptor (e.g. ZM241385) blocked Treg-mediated
      immunosuppression. The inhibition of ADA activity on effector T cells enhanced
      Treg-mediated immunosuppression. Thus, human nTreg characterized by the presence
      of CD39 and the low expression of CD26/ADA are responsible for the generation of
      adenosine, which plays a major role in Treg-mediated immunosuppression. The data
      suggest that the adenosinergic pathway represents a potential therapeutic target
      for regulation of immunosuppression in a broad variety of human diseases.

PMID- 19858206
TI  - Vav and Rac activation in B cell antigen receptor endocytosis involves Vav
      recruitment to the adapter protein LAB.
AB  - The signal transduction events supporting B cell antigen receptor (BCR)
      endocytosis are not well understood. We have identified a pathway supporting BCR
      internalization that begins with tyrosine phosphorylation of the adapter protein
      LAB. Phosphorylated LAB recruits a complex of Grb2-dynamin and the guanine
      nucleotide exchange factor Vav. Vav is required for activation of the small
      GTPases Rac1 and Rac2. All these proteins contribute to (and dynamin, Vav, and
      Rac1/2 are required for) BCR endocytosis and presentation of antigen to T cells.
      This is the first description of a sequential signal transduction pathway from
      BCR to internalization and antigen presentation.

PMID- 19858207
TI  - Kruppel-like factor 4 is a novel mediator of Kallistatin in inhibiting
      endothelial inflammation via increased endothelial nitric-oxide synthase
      expression.
AB  - Kallistatin is a plasma protein that exhibits pleiotropic effects in
      vasodilation, anti-angiogenesis, and anti-inflammation. To isolate a kallistatin
      binding protein that mediates the vascular actions of kallistatin, we screened
      and identified a positive clone from a human heart cDNA expression library by
      using an alkaline phosphatase-kallistatin fusion protein binding assay. Sequence
      analysis revealed that kallistatin-binding protein is human Kruppel-like factor 4
      (KLF4). KLF4 was localized on the plasma membrane of HEK-293 cells and
      endothelial cells overexpressing KLF4. KLF4 and kallistatin complex formation was
      identified in endothelial cells by immunoprecipitation followed by
      immunoblotting. We showed that kallistatin inhibits tumor necrosis factor-alpha
      induced NF-kappaB activation, as well as vascular cell adhesion molecule-1 and
      monocyte chemoattractant protein-1 expression in endothelial cells, whereas
      knockdown of KLF4 by small interfering RNA oligonucleotide abolished the effect
      of kallistatin. Kallistatin increased endothelial nitric-oxide synthase (eNOS)
      expression and nitric oxide levels, and these effects were also blocked by KLF4
      small interfering RNA oligonucleotide. Moreover, inhibition of eNOS by RNA
      interference or by NOS inhibitor abolished the blocking effect of kallistatin on
      vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1
      expression. In summary, we identified KLF4 as a kallistatin-binding protein,
      which has a novel role in mediating the anti-inflammatory actions of kallistatin
      via increasing eNOS expression in endothelial cells. This study provides a new
      target for modulating endothelial function in vascular disease.

PMID- 19858208
TI  - Three pairs of protease-serpin complexes cooperatively regulate the insect innate
      immune responses.
AB  - Serpins are known to be necessary for the regulation of several serine protease
      cascades. However, the mechanisms of how serpins regulate the innate immune
      responses of invertebrates are not well understood due to the uncertainty of the
      identity of the serine proteases targeted by the serpins. We recently reported
      the molecular activation mechanisms of three serine protease-mediated Toll and
      melanin synthesis cascades in a large beetle, Tenebrio molitor. Here, we purified
      three novel serpins (SPN40, SPN55, and SPN48) from the hemolymph of T. molitor.
      These serpins made specific serpin-serine protease pairs with three Toll cascade
      activating serine proteases, such as modular serine protease, Spatzle-processing
      enzyme-activating enzyme, and Spatzle-processing enzyme and cooperatively blocked
      the Toll signaling cascade and beta-1,3-glucan-mediated melanin biosynthesis.
      Also, the levels of SPN40 and SPN55 were dramatically increased in vivo by the
      injection of a Toll ligand, processed Spatzle, into Tenebrio larvae. This
      increase in SPN40 and SPN55 levels indicates that these serpins function as
      inducible negative feedback inhibitors. Unexpectedly, SPN55 and SPN48 were
      cleaved at Tyr and Glu residues in reactive center loops, respectively, despite
      being targeted by trypsin-like Spatzle-processing enzyme-activating enzyme and
      Spatzle-processing enzyme. These cleavage patterns are also highly similar to
      those of unusual mammalian serpins involved in blood coagulation and blood
      pressure regulation, and they may contribute to highly specific and timely
      inactivation of detrimental serine proteases during innate immune responses.
      Taken together, these results demonstrate the specific regulatory evidences of
      innate immune responses by three novel serpins.

PMID- 19858209
TI  - G protein pathway suppressor 2 (GPS2) is a transcriptional corepressor important
      for estrogen receptor alpha-mediated transcriptional regulation.
AB  - We have identified G protein suppressor 2 (GPS2) as a stable component of the
      SMRT corepressor complexes. GPS2 potently represses basal transcription, with the
      repression domain mapped to the N-terminal silencing mediator of retinoic acid
      and thyroid hormone receptor (SMRT)-interacting domain. Knockdown of GPS2
      abrogates, whereas overexpression potentiates, SMRT-mediated repression activity.
      The SMRT complexes are involved in 4-hydroxyl-tamoxifen (4OHT)-mediated gene
      repression by estrogen receptor alpha (ERalpha). We show that 4OHT recruits SMRT
      and GPS2 to the promoter of pS2, an ERalpha target gene, in a dynamic manner.
      Unexpectedly, we also found that estradiol (E2) promotes promoter recruitment of
      the SMRT complexes. While knockdown of GPS2 compromised 4OHT-mediated repression,
      it enhanced E2-induced expression of a reporter gene and several endogenous
      ERalpha target genes, including pS2, cyclin D1 (CCND1), progesterone receptor
      (PR), and c-MYC. Finally, we show that depletion of GPS2 or SMRT by siRNA
      promotes cell proliferation in MCF-7 breast cancer cells. Thus, we concluded that
      GPS2 is an integral component of the SMRT complexes, important for ligand
      dependent gene regulations by ERalpha and a suppressor for MCF-7 cell
      proliferation.

PMID- 19858210
TI  - Distinct roles of glycogen synthase kinase (GSK)-3alpha and GSK-3beta in
      mediating cardiomyocyte differentiation in murine bone marrow-derived mesenchymal
      stem cells.
AB  - The signaling mechanisms facilitating cardiomyocyte (CM) differentiation from
      bone marrow (BM)-derived mesenchymal stem cells (MSCs) are not well understood. 5
      Azacytidine (5-Aza), a DNA demethylating agent, induces expression of cardiac
      specific genes, such as Nkx2.5 and alpha-MHC, in mouse BM-derived MSCs. 5-Aza
      treatment caused significant up-regulation of glycogen synthase kinase (GSK)
      3beta and down-regulation of beta-catenin, whereas it stimulated GSK-3alpha
      expression only modestly. The promoter region of GSK-3beta was heavily methylated
      in control MSCs, but was demethylated by 5-Aza. Although overexpression of GSK
      3beta potently induced CM differentiation, that of GSK-3alpha induced markers of
      neuronal and chondrocyte differentiation. GSK-3 inhibitors, including LiCl, SB
      216743, and BIO, abolished 5-Aza-induced up-regulation of CM-specific genes,
      suggesting that GSK-3 is necessary and sufficient for CM differentiation in MSCs.
      Although specific knockdown of endogenous GSK-3beta abolished 5-Aza-induced
      expression of cardiac specific genes, surprisingly, that of GSK-3alpha
      facilitated CM differentiation in MSCs. Although GSK-3beta is found in both the
      cytosol and nucleus in MSCs, GSK-3alpha is localized primarily in the nucleus.
      Nuclear-specific overexpression of GSK-3beta failed to stimulate CM
      differentiation. Down-regulation of beta-catenin mediates GSK-3beta-induced CM
      differentiation in MSCs, whereas up-regulation of c-Jun plays an important role
      in mediating CM differentiation induced by GSK-3alpha knockdown. These results
      suggest that GSK-3alpha and GSK-3beta have distinct roles in regulating CM
      differentiation in BM-derived MSCs. GSK-3beta in the cytosol induces CM
      differentiation of MSCs through down-regulation of beta-catenin. In contrast, GSK
      3alpha in the nucleus inhibits CM differentiation through down-regulation of c
      Jun.

PMID- 19858211
TI  - Interactions between subunits in heterodimeric Ncd molecules.
AB  - The nonprocessive minus-end-directed kinesin-14 Ncd is involved in the
      organization of the microtubule (MT) network during mitosis. Only one of the two
      motor domains is involved in the interaction with the MT. The other head is
      tethered to the bound one. Here we prepared, purified, and characterized mutated
      Ncd molecules carrying point mutations in one of the heads, thus producing
      heterodimeric motors. The mutations tested included substitutions in Switch I and
      II: R552A, E585A, and E585D; the decoupling mutant N600K; and a deletion in the
      motor domain in one of the subunits resulting in a single-headed molecule (NcN).
      These proteins were isolated by two sequential affinity chromatography steps,
      followed by measurements of their affinities to MT, enzymatic properties, and the
      velocity of the microtubule gliding test in vitro. A striking observation is a
      low affinity of the single-headed NcN for MT both without nucleotides and in the
      presence of 5'-adenylyl-beta,gamma-imidodiphosphate, implying that the tethered
      head has a profound effect on the structure of the Ncd-MT complex. Mutated
      homodimers had no MT-activated ATPase and no motility, whereas NcN had motility
      comparable with that of the wild type Ncd. Although the heterodimers had one
      fully active and one inactive head, the ATPase and motility of Ncd heterodimers
      varied dramatically, clearly demonstrating that interactions between motor
      domains exist in Ncd. We also show that the bulk property of dimeric proteins
      that interact with the filament with only one of its heads depends also on the
      distribution of the filament-interacting subunits.

PMID- 19858212
TI  - Deletion of tumor necrosis factor-alpha receptor 1 (TNFR1) protects against diet
      induced obesity by means of increased thermogenesis.
AB  - In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger
      intracellular mechanisms that lead to resistance to the main adipostatic
      hormones, leptin and insulin. Tumor necrosis factor-alpha (TNF-alpha) is one of
      the main inflammatory factors produced during this process and its mechanistic
      role as an inducer of leptin and insulin resistance has been widely investigated.
      Most of TNF-alpha inflammatory signals are delivered by TNF receptor 1 (R1);
      however, the role played by this receptor in the context of obesity-associated
      inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1
      KO) mice are protected from diet-induced obesity due to increased thermogenesis.
      Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less
      body mass despite increased caloric intake. Visceral adiposity and mean adipocyte
      diameter are reduced and blood concentrations of insulin and leptin are lower.
      Protection from hypothalamic leptin resistance is evidenced by increased leptin
      induced suppression of food intake and preserved activation of leptin signal
      transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO
      mice present a significantly increased expression of the thermogenesis-related
      neurotransmitter, TRH. Further evidence of increased thermogenesis includes
      increased O(2) consumption in respirometry measurements, increased expressions of
      UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and
      increased O(2) consumption by isolated skeletal muscle fiber mitochondria. This
      demonstrates that TNF-alpha signaling through TNFR1 is an important mechanism
      involved in obesity-associated defective thermogenesis.

PMID- 19858213
TI  - Crystal structure of albaflavenone monooxygenase containing a moonlighting
      terpene synthase active site.
AB  - Albaflavenone synthase (CYP170A1) is a monooxygenase catalyzing the final two
      steps in the biosynthesis of this antibiotic in the soil bacterium, Streptomyces
      coelicolor A3(2). Interestingly, CYP170A1 shows no stereo selection forming equal
      amounts of two albaflavenol epimers, each of which is oxidized in turn to
      albaflavenone. To explore the structural basis of the reaction mechanism, we have
      studied the crystal structures of both ligand-free CYP170A1 (2.6 A) and complex
      of endogenous substrate (epi-isozizaene) with CYP170A1 (3.3 A). The structure of
      the complex suggests that the proximal epi-isozizaene molecules may bind to the
      heme iron in two orientations. In addition, much to our surprise, we have found
      that albaflavenone synthase also has a second, completely distinct catalytic
      activity corresponding to the synthesis of farnesene isomers from farnesyl
      diphosphate. Within the cytochrome P450 alpha-helical domain both the primary
      sequence and x-ray structure indicate the presence of a novel terpene synthase
      active site that is moonlighting on the P450 structure. This includes signature
      sequences for divalent cation binding and an alpha-helical barrel. This barrel is
      unusual because it consists of only four helices rather than six found in all
      other terpene synthases. Mutagenesis establishes that this barrel is essential
      for the terpene synthase activity of CYP170A1 but not for the monooxygenase
      activity. This is the first bifunctional P450 discovered to have another active
      site moonlighting on it and the first time a terpene synthase active site is
      found moonlighting on another protein.

PMID- 19858215
TI  - Domain motion in cytochrome P450 reductase: conformational equilibria revealed by
      NMR and small-angle x-ray scattering.
AB  - NADPH-cytochrome P450 reductase (CPR), a diflavin reductase, plays a key role in
      the mammalian P450 mono-oxygenase system. In its crystal structure, the two
      flavins are close together, positioned for interflavin electron transfer but not
      for electron transfer to cytochrome P450. A number of lines of evidence suggest
      that domain motion is important in the action of the enzyme. We report NMR and
      small-angle x-ray scattering experiments addressing directly the question of
      domain organization in human CPR. Comparison of the (1)H-(15)N heteronuclear
      single quantum correlation spectrum of CPR with that of the isolated FMN domain
      permitted identification of residues in the FMN domain whose environment differs
      in the two situations. These include several residues that are solvent-exposed in
      the CPR crystal structure, indicating the existence of a second conformation in
      which the FMN domain is involved in a different interdomain interface. Small
      angle x-ray scattering experiments showed that oxidized and NADPH-reduced CPRs
      have different overall shapes. The scattering curve of the reduced enzyme can be
      adequately explained by the crystal structure, whereas analysis of the data for
      the oxidized enzyme indicates that it exists as a mixture of approximately equal
      amounts of two conformations, one consistent with the crystal structure and one a
      more extended structure consistent with that inferred from the NMR data. The
      correlation between the effects of adenosine 2',5'-bisphosphate and NADPH on the
      scattering curve and their effects on the rate of interflavin electron transfer
      suggests that this conformational equilibrium is physiologically relevant.

PMID- 19858214
TI  - Characterization of celastrol to inhibit hsp90 and cdc37 interaction.
AB  - The molecular chaperone heat shock protein 90 (Hsp90) is required for the
      stabilization and conformational maturation of various oncogenic proteins in
      cancer. The loading of protein kinases to Hsp90 is actively mediated by the
      cochaperone Cdc37. The crucial role of the Hsp90-Cdc37 complex has made it an
      exciting target for cancer treatment. In this study, we characterize Hsp90 and
      Cdc37 interaction and drug disruption using a reconstituted protein system. The
      GST pull-down assay and ELISA assay show that Cdc37 binds to ADP-bound/nucleotide
      free Hsp90 but not ATP-bound Hsp90. Celastrol disrupts Hsp90-Cdc37 complex
      formation, whereas the classical Hsp90 inhibitors (e.g. geldanamycin) have no
      effect. Celastrol inhibits Hsp90 ATPase activity without blocking ATP binding.
      Proteolytic fingerprinting indicates celastrol binds to Hsp90 C-terminal domain
      to protect it from trypsin digestion. These data suggest that celastrol may
      represent a new class of Hsp90 inhibitor by modifying Hsp90 C terminus to
      allosterically regulate its chaperone activity and disrupt Hsp90-Cdc37 complex.

PMID- 19858216
TI  - Each monomer of the dimeric accessory protein for human mitochondrial DNA
      polymerase has a distinct role in conferring processivity.
AB  - The accessory protein polymerase (pol) gammaB of the human mitochondrial DNA
      polymerase stimulates the synthetic activity of the catalytic subunit. pol gammaB
      functions by both accelerating the polymerization rate and enhancing polymerase
      DNA interaction, thereby distinguishing itself from the accessory subunits of
      other DNA polymerases. The molecular basis for the unique functions of human pol
      gammaB lies in its dimeric structure, where the pol gammaB monomer proximal to
      pol gammaA in the holoenzyme strengthens the interaction with DNA, and the distal
      pol gammaB monomer accelerates the reaction rate. We further show that human pol
      gammaB exhibits a catalytic subunit- and substrate DNA-dependent dimerization. By
      duplicating the monomeric pol gammaB of lower eukaryotes, the dimeric mammalian
      proteins confer additional processivity to the holoenzyme polymerase.

PMID- 19858217
TI  - A turn-like structure "KKPE" segment mediates the specific binding of viral
      protein A27 to heparin and heparan sulfate on cell surfaces.
AB  - Vaccinia viral envelope protein A27 (110 amino acids) specifically interacts with
      heparin (HP) or heparan sulfate (HS) proteoglycans for cell surface attachment.
      To examine the binding mechanism, a truncated soluble form of A27 (sA27-aa;
      residues 21-84 of A27) with Cys(71) and Cys(72) mutated to Ala was used as the
      parent molecule. sA27-aa consists of two structurally distinct domains, a
      flexible Arg/Lys-rich heparin-binding site (HBS) (residues 21-32;
      (21)STKAAKKPEAKR(32)) and a rigid coiled-coil domain (residues 43-84), both
      essential for the specific binding. As shown by surface plasmon resonance (SPR),
      the binding affinity of sA27-aa for HP (K(A) = 1.25 x 10(8) m(-1)) was
      approximately 3 orders of magnitude stronger than that for nonspecific binding,
      such as to chondroitin sulfate (K(A) = 1.65 x 10(5) m(-1)). Using site-directed
      mutagenesis of HBS and solution NMR, we identified a "KKPE" segment with a turn
      like conformation that mediates specific HP binding. In addition, a double mutant
      T22K/A25K in which the KKPE segment remained intact showed an extremely high
      affinity for HP (K(A) = 1.9 x 10(11) m(-1)). Importantly, T22K/A25K retained the
      binding specificity for HP and HS but not chondroitin sulfate, as shown by in
      vitro SPR and in vivo cell adhesion and competitive binding assays. Molecular
      modeling of the HBS was performed by dynamics simulations and provides an
      explanation of the specific binding mechanism in good agreement with the site
      directed mutagenesis and SPR results. We conclude that a turn-like structure
      introduced by the KKPE segment in vaccinia viral envelope protein A27 is
      responsible for its specific binding to HP and to HS on cell surfaces.

PMID- 19858218
TI  - Syndecan-2 functions as a docking receptor for pro-matrix metalloproteinase-7 in
      human colon cancer cells.
AB  - Although elevated syndecan-2 expression is known to be crucial for the
      tumorigenic activity in colon carcinoma cells, how syndecan-2 regulates colon
      cancer is unclear. In human colon adenocarcinoma tissue samples, we found that
      both mRNA and protein expression of syndecan-2 were increased, compared with the
      neighboring normal epithelium, suggesting that syndecan-2 plays functional roles
      in human colon cancer cells. Consistent with this notion, syndecan-2
      overexpressing HT-29 colon adenocarcinoma cells showed enhanced
      migration/invasion, anchorage-independent growth, and primary tumor formation in
      nude mice, paralleling their morphological changes into highly tumorigenic cells.
      In addition, our experiments revealed that syndecan-2 enhanced both expression
      and secretion of matrix metalloproteinase-7 (MMP-7), directly interacted with pro
      MMP-7, and potentiated the enzymatic activity of pro-MMP-7 by activating its
      processing into the active MMP-7. Collectively, these data strongly suggest that
      syndecan-2 functions as a docking receptor for pro-MMP-7 in colon cancer cells.

PMID- 19858219
TI  - Abnormal expression of collagen IV in lens activates unfolded protein response
      resulting in cataract.
AB  - Human diseases caused by mutations in extracellular matrix genes are often
      associated with an increased risk of cataract and lens capsular rupture. However,
      the underlying mechanisms of cataract pathogenesis in these conditions are still
      unknown. Using two different mouse models, we show that the accumulation of
      collagen chains in the secretory pathway activates the stress signaling pathway
      termed unfolded protein response (UPR). Transgenic mice expressing ectopic Col4a3
      and Col4a4 genes in the lens exhibited activation of IRE1, ATF6, and PERK
      associated with expansion of the endoplasmic reticulum and attenuation of general
      protein translation. The expression of the transgenes had adverse effects on lens
      fiber cell differentiation and eventually induced cell death in a group of
      transgenic fiber cells. In Col4a1(+/Deltaex40) mutant mice, the accumulation of
      mutant chains also caused low levels of UPR activation. However, cell death was
      not induced in mutant lenses, suggesting that low levels of UPR activation are
      not proapoptotic. Collectively, the results provide in vivo evidence for a role
      of UPR in cataract formation in response to accumulation of terminally unfolded
      proteins in the endoplasmic reticulum.

PMID- 19858220
TI  - Dephosphorylation of threonine 38 is required for nuclear translocation and
      activation of human xenobiotic receptor CAR (NR1I3).
AB  - Upon activation by therapeutics, the nuclear xenobiotic/ constitutive
      active/androstane receptor (CAR) regulates various liver functions ranging from
      drug metabolism and excretion to energy metabolism. CAR can also be a risk factor
      for developing liver diseases such as hepatocellular carcinoma. Here we have
      characterized the conserved threonine 38 of human CAR as the primary residue that
      regulates nuclear translocation and activation of CAR. Protein kinase C
      phosphorylates threonine 38 located on the alpha-helix spanning from residues 29
      42 that constitutes a part of the first zinc finger and continues into the region
      between the zinc fingers. Molecular dynamics study has revealed that this
      phosphorylation may destabilize this helix, thereby inactivating CAR binding to
      DNA as well as sequestering it in the cytoplasm. We have found, in fact, that
      helix-stabilizing mutations reversed the effects of phosphorylation.
      Immunohistochemical study using an anti-phospho-threonine 38 peptide antibody
      has, in fact, demonstrated that the classic CAR activator phenobarbital
      dephosphorylates the corresponding threonine 48 of mouse CAR in the cytoplasm of
      mouse liver and translocates CAR into the nucleus. These results define CAR as a
      cell signal-regulated constitutive active nuclear receptor. These results also
      provide phosphorylation/dephosphorylation of the threonine as the primary drug
      target for CAR activation.

PMID- 19858223
TI  - The ovary: from basic research to clinic.

PMID- 19858221
TI  - Involvement of Galectin-3 with vascular cell adhesion molecule-1 in growth
      regulation of mouse BALB/3T3 cells.
AB  - beta-Galactose residues on N-glycans have been implicated to be involved in
      growth regulation of cells. In the present study we compared the galactosylation
      of cell surface N-glycans of mouse Balb/3T3 cells between 30 and 100% densities
      and found the beta-1,4-galactosylation of N-glycans increases predominantly in a
      100-kDa protein band on lectin blot analysis in combination with digestions by
      diplococcal beta-galactosidase and N-glycanase. When cells at 100% density were
      treated with jack bean beta-galactosidase, the incorporation of 5
      bromodeoxyuridine into the cells was stimulated in a dose-dependent manner,
      suggesting the involvement of the galactose residues in growth regulation of
      cells. A galactose-binding protein was isolated from the plasma membranes of
      cells at 100% density by affinity chromatography using an asialo-transferrin
      Sepharose column and found to be galectin-3 as revealed by mass spectrometric
      analysis. The addition of recombinant galectin-3 into cells at 50% density
      inhibited the incorporation of 5-bromodeoxyuridine in a dose-dependent manner,
      but the inhibition was prevented with haptenic sugar. An immunocytochemical study
      showed that galectin-3 is present at the surface of cells at 100% density but not
      at 30% density where it locates inside the cells. Several glycoproteins bind to a
      galectin-3-immobilized column, a major of which was identified as vascular cell
      adhesion molecule (VCAM)-1. Immunocytochemical studies showed that some galectin
      3 and VCAM-1 co-localize at the surface of cells at 100% density, indicating that
      the binding of galectin-3 secreted from cells to VCAM-1 is one of the pathways
      involved in the growth regulation of Balb/3T3 cells.

PMID- 19858224
TI  - Novel gene rearrangements in transformed breast cells identified by high
      resolution breakpoint analysis of chromosomal aberrations.
AB  - Chromosomal copy number alterations and chromosomal rearrangements are frequent
      mutations in human cancer. Unlike copy number alterations, little is known about
      the role and occurrence of chromosomal rearrangements in breast cancer. This may
      be due to the fact that chromosome-based breakpoint analysis is widely restricted
      to cultured cells. In order to identify gene rearrangements in breast cancer, we
      studied the chromosomal breakpoints in radiation-transformed epithelial breast
      cell lines using a high-resolution array-based approach using 1 Mb bacterial
      artificial chromosome (BAC) arrays. The breakpoints were further narrowed down by
      fluorescence in situ hybridisation (FISH) with clones from the 32 k BAC library.
      The analysis of the cell lines B42-11 and B42-16 revealed rearrangements of
      chromosomes 7, 8, 10 and 12. We identified the genes Has2, Grid1, Ret, Cpm, Tbx3,
      Tbx5, Tuba1a, Wnt1 and Arf3 within the breakpoint regions. Quantitative RT-PCR
      showed a deregulated expression of all of these candidate genes except for Tbx5
      and Tbx3. This is the first study demonstrating gene rearrangements and their
      deregulated mRNA expression in radiation-transformed breast cells. Since the gene
      rearrangements occurred in the transformed and tumourigenic cell lines only, it
      is likely that these were generated in conjunction with malignant transformation
      of the epithelial breast cells and therefore might reflect early molecular events
      in breast carcinogenesis. Initial studies indicate that these gene alterations
      are also found in sporadic breast cancers.

PMID- 19858225
TI  - Synaptically induced sodium signals in hippocampal astrocytes in situ.
AB  - Astrocytes are in close contact to excitatory synapses and express transporters
      which mediate the sodium-dependent uptake of glutamate. In cultured astrocytes,
      selective activation of glutamate transport results in sodium elevations which
      stimulate Na(+)/K(+)-ATPase and glucose uptake, indicating that synaptic release
      of glutamate might couple excitatory neuronal activity to glial sodium
      homeostasis and metabolism. Here, we analysed intracellular sodium transients
      evoked by synaptic stimulation in acute mouse hippocampal slices using
      quantitative sodium imaging with the sodium-sensitive fluorescent indicator dye
      SBFI (sodium-binding benzofuran isophthalate). We found that short bursts of
      Schaffer collateral stimulation evoke sodium transients in the millimolar range
      in both CA1 pyramidal neurons and in SR101-positive astrocytes of the stratum
      radiatum. At low stimulation intensities, glial sodium transients were confined
      to one to two primary branches and adjacent fine processes and only weakly
      invaded the soma. Increasing the number of activated afferent fibres by
      increasing the stimulation intensity elicited global sodium transients detectable
      in the processes as well as the somata of astrocytes. Pharmacological analysis
      revealed that neuronal sodium signals were mainly attributable to sodium influx
      through ionotropic glutamate receptors. Activation of ionotropic receptors also
      contributed to glial sodium transients, while TBOA-sensitive glutamate transport
      was the major pathway responsible for sodium influx into astrocytes. Our results
      thus establish that glutamatergic synaptic transmission in the hippocampus
      results in sodium transients in astrocytes that are mainly mediated by activation
      of glutamate transport. They support the proposed link between excitatory
      synaptic activity, glutamate uptake and sodium signals in astrocytes of the
      hippocampus.

PMID- 19858226
TI  - Differential induction of bidirectional long-term changes in neurotransmitter
      release by frequency-coded patterns at the cerebellar input.
AB  - Sensory stimulation conveys spike discharges of variable frequency and duration
      along the mossy fibres of cerebellum raising the question of whether and how
      these patterns determine plastic changes at the mossy fibre-granule cell synapse.
      Although various combinations of high-frequency bursts and membrane
      depolarization can induce NMDA receptor-dependent long-term depression (LTD) and
      long-term potentiation (LTP), the effect of different discharge frequencies
      remained unknown. Here we show that low-frequency mossy fibre stimulation (100
      impulses1 Hz) induces mGlu receptor-dependent LTD. For various burst frequencies,
      the plasticity-[Ca(2+)](i) relationship was U-shaped resembling the Bienenstok
      Cooper-Munro (BCM) learning rule. Moreover, LTD expression was associated with
      increased paired-pulse ratio, coefficient of variation and failure rate, and with
      a decrease in release probability, therefore showing changes opposite to those
      characterizing LTP. The plasticity-[Ca(2+)](i) relationship and the changes in
      neurotransmitter release measured by varying induction frequencies were
      indistinguishable from those obtained by varying high-frequency burst duration.
      These results suggest that different glutamate receptors converge onto a final
      common mechanism translating the frequency and duration of mossy fibre discharges
      into a regulation of the LTP/LTD balance, which may play an important role in
      adapting spatio-temporal signal transformations at the cerebellar input stage.

PMID- 19858227
TI  - Motor cortex plasticity induced by paired associative stimulation is enhanced in
      physically active individuals.
AB  - Recent evidence indicates that regular physical activity enhances brain
      plasticity (i.e. the ability to reorganise neural connections) and improves
      neurocognitive function. However, the effect of regular physical activity on
      human motor cortex function is unknown. The purpose of this study was to examine
      motor cortex plasticity for a small hand muscle in highly active and sedentary
      individuals. Electromyographic recordings were obtained from the left abductor
      pollicis brevis (APB) muscle of 14 active and 14 sedentary subjects (aged 18-38
      yrs). The extent of physical activity was assessed by questionnaire, where the
      physically active subjects performed >150 min per day moderate-to-vigorous
      aerobic activity on at least 5 days per week, whereas the sedentary group
      performed <20 min per day of physical activity on no more than 3 days per week.
      Transcranial magnetic stimulation (TMS) of the right hemisphere was used to
      assess changes in APB motor-evoked potentials (MEPs), input-output curve (IO
      curve), short-interval intracortical inhibition (SICI) and cortical silent period
      (CSP). Neuroplastic changes were induced using paired-associative stimulation
      (PAS), which consisted of 90 paired stimuli (0.05 Hz for 30 min) of median nerve
      electrical stimulation at the wrist followed 25 ms later by TMS to the hand area
      of motor cortex. The IO curve slope was 35% steeper in individuals with increased
      physical activity (combined before and after PAS, P < 0.05), suggesting increased
      motor cortex excitability, although there was no difference in SICI or CSP
      between groups. PAS induced an increase in MEP amplitude in the physically active
      subjects (54% increase compared with before, P < 0.01), but no significant
      facilitation in the sedentary subjects. We conclude that participation in regular
      physical activity may offer global benefits to motor cortex function that
      enhances neuroplasticity, which could improve motor learning and
      neurorehabilitation in physically active individuals.

PMID- 19858229
TI  - Effects of pulmonary rehabilitation in patients with restrictive lung diseases.
AB  - BACKGROUND: Pulmonary rehabilitation programs improve exercise tolerance, muscle
      strength, and dyspnea in patients with COPD. The aim of the study was to assess
      prospectively the effectiveness and feasibility of pulmonary rehabilitation in
      patients with restrictive lung diseases. METHODS: In a prospective,
      nonrandomized, noncontrolled study, patients with an established diagnosis of
      restrictive lung disease (RLD) participated in a 24-week outpatient
      multidisciplinary rehabilitation program. Pulmonary function, exercise capacity,
      muscle force, and dyspnea were measured at inclusion, after 12 and 24 weeks of
      rehabilitation. Primary outcome was the change in 6-min walk distance (6MWD)
      after 12 weeks of rehabilitation. RESULTS: Twenty-nine patients out of 31
      patients (57 +/- 17 years of age; 21 men; FEV(1): 1.4 +/- 0.7 L) completed the 12
      week rehabilitation program and 26 patients the 24-week rehabilitation program.
      At inclusion, exercise tolerance (maximal oxygen consumption [V(O(2))max]: 63% +/
      27% predicted; 6MWD: 390 +/- 140 m) and quadriceps force ([QF] 61% +/- 21%
      predicted) were reduced, and dyspnea, assessed using the Chronic Respiratory
      Disease Questionnaire (CRDQ), was increased (CRDQ item dyspnea [CRDQd]: 16 +/- 6
      points). Exercise capacity, muscle force, and CRDQd improved significantly after
      12 weeks (6MWD: 445 +/- 142 m; V(O(2))max: 69% +/- 30% predicted; QF: 73% +/- 25%
      predicted; CRDQd: 20 +/- 6 points) (P < .05). Further improvements were noted
      after 24 weeks (6MWD: 463 +/- 146 m; CRDQd: 22 +/- 6 points). CONCLUSIONS:
      Patients with RLD respond well after 12 weeks of pulmonary rehabilitation, and
      even better results were seen after 24 weeks. Clinically significant improvements
      were obtained in the majority of the patients after 24 weeks.

PMID- 19858228
TI  - Relationship between plasma free fatty acid, intramyocellular triglycerides and
      long-chain acylcarnitines in resting humans.
AB  - We hypothesized that plasma non-esterified fatty acids (NEFA) are trafficked
      directly to intramyocellular long-chain acylcarnitines (imLCAC) rather than
      transiting intramyocellular triglycerides (imTG) on the way to resting muscle
      fatty acid oxidation. Overnight fasted adults (n = 61) received intravenous
      infusions of [U-(13)C]palmitate (0400-0830 h) and [U-(13)C]oleate (0800-1400 h)
      labelling plasma NEFA, imTG, imLCAC and im-non-esterified FA (imNEFA). Two muscle
      biopsies (0830 and 1400 h) were performed following 6 h, overlapping, sequential
      palmitate/oleate tracer infusions. Enrichment of plasma palmitate was
      approximately 15 times greater than enrichment of imTG, imNEFA-palmitate and im
      palmitoyl-carnitine. Fatty acid enrichment in LCAC was correlated with imTG and
      imNEFA; there was a significant correlation between imTG concentrations and
      imLCAC concentrations in women (r = 0.51, P = 0.005), but not men (r = 0.30, P =
      0.11). We estimated that approximately 11% of NEFA were stored in imTG. imTG NEFA
      storage was correlated only with NEFA concentrations (r = 0.52, P = 0.004) in
      women and with V(O(2),peak) (r = 0.45, P = 0.02) in men. At rest, plasma NEFA are
      trafficked largely to imTG before they enter LCAC oxidative pools; thus, imTG are
      an important, central pool that regulates the delivery of fatty acids to the
      intracellular environment. Factors relating to plasma NEFA storage into imTG
      differ in men and women.

PMID- 19858230
TI  - Relationship of indices of inflammation and thrombogenesis to arrhythmia burden
      in paroxysmal atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with a high risk of stroke.
      The contribution of arrhythmia to events is clear in sustained forms of AF, but
      in paroxysmal AF, presently available data have yet to identify what proportion
      of time spent in AF (ie, arrhythmia burden [AFB]) is of clinical relevance. We
      aimed to assess this relationship using surrogate blood markers for the
      hypercoagulable state associated with AF. METHODS: One hundred twenty-one
      consecutive outpatients (mean age 74.7 +/- 7.8 years; 73 [60.3%] men) with
      pacemakers capable of arrhythmia detection were recruited. AFB was assessed over
      a 1-month period and classified as AFB = 0%, 0.1% to 10%, 10.1% to 50%, or > 50%.
      RESULTS: Baseline characteristics and comorbidities were comparable between
      groups. There were no significant differences in levels of soluble E-selectin (sE
      selectin), von Willebrand factor (vWf), high-sensitivity C-reactive protein,
      interleukin-6, soluble P-selectin (sP-selectin), or tissue factor (TF) across the
      four patient groups. Levels of plasma brain natriuretic peptide (BNP) were
      approximately twofold greater in the group with the highest AFB (P < .001).
      Following a stepwise multiple linear regression analysis, age was a significant
      predictor of vWf (P = .010), sP-selectin (P = .042), and BNP (P = .012). Left
      ventricular fractional shortening was predictive of BNP (P = .001) and sE
      selectin (P = .012). Anticoagulation was a predictor of vWf levels (P = .005),
      and hypertension was predictive of TF (P < .001). CONCLUSION: Given no
      appreciable difference in levels of prothrombotic markers in relation to AFB in
      this study, it is plausible that these abnormalities do, in fact, relate to
      underlying risk factors, and that such patients should be anticoagulated if risk
      factors dictate. Thus, AFB per se should probably not influence the decision to
      anticoagulate, but rather the presence of AF combined with clinical risk scoring
      should remain the predominant tool for stroke risk assessment.

PMID- 19858231
TI  - Occurrence of coronary collateral vessels in patients with sleep apnea and total
      coronary occlusion.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is thought to act as a coronary risk
      factor. There is emerging evidence that intermittent phases of hypoxia might
      contribute to alterations of the cardiovascular system. We hypothesized that OSA
      syndrome (OSAS) might be accompanied by an increased coronary collateral vessel
      (CCV) development in patients with total coronary occlusion. METHODS: Thirty-four
      patients with total coronary occlusions were classified according to the apnea
      hypopnea index (AHI) (OSAS: AHI > 10/h; non-OSAS: AHI < 10/h). CCVs were scored
      by visual analysis and were analyzed according to the Cohen and Rentrop grading
      system. RESULTS: There was no significant discrepancy between the groups
      concerning the prevalence of age, gender, the presence of hypertension, smoking,
      or diabetes mellitus. There was no difference in left ventricular systolic
      function (ejection fraction 53% +/- 20% vs 61% +/- 20%, P = .29) or left
      ventricular end-diastolic pressure (22.6 +/- 8.5 mm Hg vs 18.5 +/- 7.7 mm Hg, P =
      .41). OSAS showed a higher Rentrop score compared with non-OSAS (1.61 +/- 1.2 vs
      2.4 +/- 0.7, P = .02). CONCLUSIONS: These findings suggest that CCV development
      is augmented in patients with OSA.

PMID- 19858232
TI  - Comparative study of three different catheters for CT imaging-bronchoscopy-guided
      radiofrequency ablation as a potential and novel interventional therapy for lung
      cancer.
AB  - BACKGROUND: We previously reported that bronchoscopy-guided, internally cooled
      radiofrequency ablation (RFA) in normal sheep lung was a safe, effective, and
      feasible procedure without major complications. PURPOSES: The aim of this study
      was to evaluate the safety, effectiveness, and feasible conditions of
      bronchoscopy-guided, internally cooled RFA as a clinical application for non
      small cell lung cancer (NSCLC). METHODS: Ten patients pathologically diagnosed
      with NSCLC and the clinical stage of T1N0M0 were enrolled in the study. Three
      types of internally cooled electrode catheter tips were prepared using different
      procedure conditions involving ablation time: an internally cooled electrode with
      a 5-mm cylindrical active tip at a power output of 20 W, flow rate of 50 mL/min,
      and an ablation time of 30 s (n = 3), an electrode with an 8-mm active tip with
      four beads at 20 W, 50 mL/min, and 40 s (n = 3), and an electrode with a 10-mm
      active tip with five beads at 20 W, 50 mL/min, and 50 s (n = 4). CT image-guided,
      bronchoscopy-guided, internally cooled RFA was performed, and the patients
      underwent standard lung resection therapy. The resected lung tissue was examined
      histopathologically to assess the ablated areas. RESULTS: Ablated areas
      pathologically evaluated with the 10-mm active tip were significantly larger than
      those with the 5-mm tip. Thus, the ablated areas were enlarged depending on the
      tip length and prolonged ablation time. There were no complications during RFA,
      such as bronchial bleeding or pneumothorax. CONCLUSIONS: CT imaging-bronchoscopy
      guided, internally cooled RFA in humans is a safe and feasible procedure that
      could become a potential therapeutic tool for local control in medically
      inoperable patients with stage I NSCLC.

PMID- 19858234
TI  - A prospective multicenter study of competency metrics and educational
      interventions in the learning of bronchoscopy among new pulmonary fellows.
AB  - BACKGROUND: Learning medical procedures relies predominantly on the
      apprenticeship model, and competency is established based on the number of
      performed procedures. Our study aimed to establish bronchoscopy competency
      metrics based on performance and enhanced learning with educational
      interventions. METHODS: We conducted a prospective study of the acquisition of
      bronchoscopy skills and cognitive knowledge in two successive cohorts of new
      pulmonary fellows between July 5, 2006, and June 30, 2008. At prespecified
      milestones, validated tools were used for testing: the Bronchoscopy Skills and
      Tasks Assessment Tool (BSTAT), an objective evaluation of bronchoscopy skills
      with scores ranging from 0 to 24, and written multiple-choice questions
      examinations. The first cohort received training in bronchoscopy as per the
      standards set by each institution, whereas the second cohort received educational
      interventions, including training in simulation bronchoscopy and an online
      bronchoscopy curriculum. RESULTS: There was significant variation among study
      participants in bronchoscopy skills at their 50th bronchoscopy, the minimum
      number previously set to achieve competency in bronchoscopy. An educational
      intervention of incorporating simulation bronchoscopy enhanced the speed of
      acquisition of bronchoscopy skills, as shown by the statistically significant
      improvement in mean BSTAT scores for seven of the eight milestone bronchoscopies
      (P < .05). The online curriculum did not improve the performance on the written
      tests; however, compliance of the learners with the curriculum was low.
      CONCLUSIONS: Performance-based competency metrics can be used to evaluate
      bronchoscopy skills. Educational interventions, such as simulation-based
      training, accelerated the acquisition of bronchoscopy skills among first-year
      pulmonary fellows as assessed by a validated objective assessment tool.

PMID- 19858235
TI  - Familial clustering of pulmonary nontuberculous mycobacterial disease.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) are environmental organisms
      associated with pulmonary disease without person-to-person transmission. Although
      genetic causes of disseminated NTM infection are well characterized, genetic
      causes for most human susceptibility to pulmonary NTM infection have not been
      determined. METHODS: Family histories for relevant disease characteristics were
      obtained as part of an ongoing natural history study. Six families were
      identified in which at least two blood relatives had pulmonary NTM. A systematic
      review of medical records extracted data relevant to pulmonary infection and
      baseline demographics. Data were reconfirmed by telephone interviews. RESULTS:
      Familial clustering of pulmonary NTM was proven in six families. Four of the
      families were white, and the majority of affected individuals were women. The
      average age at diagnosis was 56.4 +/- 10.7 years, the average height was 167.5 +/
      8.7 cm, and the mean BMI was 22.0 +/- 2.98 kg/m(2). Scoliosis was present in
      31%. Five of 12 patients had cystic fibrosis transmembrane conductance regulator
      gene variations, but none had classic cystic fibrosis. Infections were caused by
      both slow and rapid growing mycobacteria, including Mycobacterium avium,
      Mycobacterium intracellulare, Mycobacterium kansasii, Mycobacterium abscessus,
      and Mycobacterium massiliense. Family members were typically infected with
      different species of NTM. CONCLUSION: We identified six familial clusters of
      pulmonary NTM infection, suggesting that there are genetic factors contributing
      to host susceptibility to pulmonary infection with NTM among some individuals
      with nodular bronchiectatic disease.

PMID- 19858236
TI  - Polybrominated diphenyl ethers cause oxidative stress in human umbilical vein
      endothelial cells.
AB  - Polybrominated diphenyl ethers (PBDEs) are used as flame retardants to prevent
      combustion in consumer products, such as electronics, construction materials, and
      textiles and, therefore, have become important commercial substances. PBDEs were
      also detected in maternal blood, breast milk, umbilical cord blood, and cord
      tissue, thereby indicating that fetuses were also exposed to PBDEs. The purpose
      of this study is to identify the effect of PBDEs on human umbilical vein
      endothelial cells (HUVECs). Cultured HUVECs were exposed to a commercial mixture
      of penta-BDE (DE71), octa-BDE (DE79), and deca-BDE (DE83). Each gene expression
      that was altered in DNA microarray was confirmed by real-time reverse
      transcription-polymerase chain reaction and Western blotting analysis. The
      results indicated that gene expressions concerning antioxidant system, i.e.,
      thioredoxin family, 24-dehydrocholesterol reductase (DHCR24), and tumor
      suppressor protein p53, were altered by PBDEs exposure in HUVECs. Moreover, it
      was demonstrated that thioredoxin-interacting protein (TXNIP) was a target gene
      in exposure to DE71 and DE79 in HUVECs, by drastically decreasing time-dependent
      TXNIP expression in HUVECs.

PMID- 19858233
TI  - Prognostic and pathogenetic value of combining clinical and biochemical indices
      in patients with acute lung injury.
AB  - BACKGROUND: No single clinical or biologic marker reliably predicts clinical
      outcomes in acute lung injury (ALI)/ARDS. We hypothesized that a combination of
      biologic and clinical markers would be superior to either biomarkers or clinical
      factors alone in predicting ALI/ARDS mortality and would provide insight into the
      pathogenesis of clinical ALI/ARDS. METHODS: Eight biologic markers that reflect
      endothelial and epithelial injury, inflammation, and coagulation (von Willebrand
      factor antigen, surfactant protein D [SP-D]), tumor necrosis factor receptor-1,
      interleukin [IL]-6, IL-8, intercellular adhesion molecule-1, protein C,
      plasminogen activator inhibitor-1) were measured in baseline plasma from 549
      patients in the ARDSNet trial of low vs high positive end-expiratory pressure.
      Mortality was modeled with multivariable logistic regression. Predictors were
      selected using backward elimination. Comparisons between candidate models were
      based on the receiver operating characteristics (ROC) and tests of integrated
      discrimination improvement. RESULTS: Clinical predictors (Acute Physiology And
      Chronic Health Evaluation III [APACHE III], organ failures, age, underlying
      cause, alveolar-arterial oxygen gradient, plateau pressure) predicted mortality
      with an area under the ROC curve (AUC) of 0.82; a combination of eight biomarkers
      and the clinical predictors had an AUC of 0.85. The best performing biomarkers
      were the neutrophil chemotactic factor, IL-8, and SP-D, a product of alveolar
      type 2 cells, supporting the concept that acute inflammation and alveolar
      epithelial injury are important pathogenetic pathways in human ALI/ARDS.
      CONCLUSIONS: A combination of biomarkers and clinical predictors is superior to
      clinical predictors or biomarkers alone for predicting mortality in ALI/ARDS and
      may be useful for stratifying patients in clinical trials. From a pathogenesis
      perspective, the degree of acute inflammation and alveolar epithelial injury are
      highly associated with the outcome of human ALI/ARDS.

PMID- 19858237
TI  - The impact of different biocompatible coated cardiopulmonary bypass circuits on
      inflammatory response and oxidative stress.
AB  - This study was to compare the impact of different biocompatible coated circuits
      on inflammatory response and oxidative stress induced during cardiopulmonary
      bypass (CPB). Seventy-eight patients undergoing elective coronary artery bypass
      grafting (CABG) with CPB were randomly assigned to five groups with different
      biocompatible coated circuits: Trillium, Bioline, Phosphorylcholine,
      Polymethoxyethyl acrylate (PMEA), and the uncoated control group. Blood was drawn
      at three different time points: before CPB, 6 and 72 hours post CPB. Unlike the
      Trillium group, serum levels of TNF-alpha in the Bioline and Phosphorylcholine
      groups significantly increased only at 72 hours post CPB (p < 0.05). Serum levels
      of IL-6 significantly increased at 6 and 72 hours post CPB in all groups (p <
      0.01). The Trillium group showed a significant increase of IL-10 compared to the
      control group at 72 hours post CPB (p < 0.05). Serum levels of NOx in the
      Phosphorylcholine group significantly decreased at 6 hours post CPB compared to
      baseline (p < 0.05). Both the Bioline and Phosphorylcholine groups showed
      statistical decreases in serum NOx levels compared with other groups at 6 hours
      post CPB (p < 0.05). A significant difference in NOx levels between the Bioline
      and the control group was also observed at 72 hours post CPB. Myeloperoxidase
      levels were significantly elevated at 6 and 72 hours post CPB in all groups (p <
      0.05). Inflammatory response and oxidative stress are elevated during CABG with
      CPB. Heparin-coated and the Phosphorylcholine-coated circuits induce less
      inflammatory responses and oxidative stress compared to other circuits.

PMID- 19858238
TI  - Fixing the fatal flaw in emergency planning.

PMID- 19858240
TI  - Diagnoses during follow-up of patients presenting with fatigue in primary care.
AB  - BACKGROUND: Little is known about the distribution of diagnoses that account for
      fatigue in patients in primary care. We evaluated the diagnoses established
      within 1 year after presentation with fatigue in primary care that were possibly
      associated with the fatigue. METHODS: We conducted a prospective observational
      cohort study with 1-year follow-up. We included adult patients who presented with
      a new episode of fatigue between June 2004 and January 2006. We extracted data on
      diagnoses during the follow-up period from the patients' medical records as well
      as data on pre-existing chronic diseases. RESULTS: Of the 571 patients for whom
      diagnostic data were available, 268 (46.9%) had received one or more diagnoses
      that could be associated with fatigue. The diagnoses were diverse and mostly
      included symptom diagnoses, with main categories being musculoskeletal (19.4%)
      and psychological problems (16.5%). Clear somatic pathology was diagnosed in 47
      (8.2%) of the patients. Most diagnoses were not made during the consultation when
      fatigue was presented. INTERPRETATION: Only a minority of patients were diagnosed
      with serious pathology. Half of the patients did not receive any diagnosis that
      could explain their fatigue. Nevertheless, because of the wide range of
      conditions and symptoms that may explain or co-occur with the fatigue, fatigue is
      a complex problem that deserves attention not only as a symptom of underlying
      specific disease.

PMID- 19858241
TI  - Clinical images: Purpura fulminans caused by meningococcemia.

PMID- 19858242
TI  - Allergic contact dermatitis caused by diclofenac cream.

PMID- 19858244
TI  - Appointment of Pfizer executive to CIHR stirs controversy.

PMID- 19858245
TI  - Privacy concerns raised over "secondary use" of health records.

PMID- 19858246
TI  - Black mark for Dalhousie medical school.

PMID- 19858247
TI  - Malawi health workers grapple with rising incidence of rape.

PMID- 19858243
TI  - Management of acute asthma in adults in the emergency department: nonventilatory
      management.

PMID- 19858248
TI  - United States faces dentist shortage.

PMID- 19858249
TI  - Dispatch from the medical front. Fees can serve as deterrents to Cambodian health
      care.

PMID- 19858250
TI  - Pharmacokinetic properties of azithromycin in pregnancy.
AB  - Azithromycin (AZI) is an azalide antibiotic with antimalarial activity that is
      considered safe in pregnancy. To assess its pharmacokinetic properties when
      administered as intermittent preventive treatment in pregnancy (IPTp), two 2-g
      doses were given 24 h apart to 31 pregnant and 29 age-matched nonpregnant Papua
      New Guinean women. All subjects also received single-dose sulfadoxine
      pyrimethamine (SP) (1,500 mg or 75 mg) or chloroquine (450-mg base daily for 3
      days). Blood samples were taken at 0, 1, 2, 3, 6, 12, 24, 32, 40, 48, and 72 h
      and on days 4, 5, 7, 10, and 14 for AZI assay by ultra-high-performance liquid
      chromatography-tandem mass spectrometry. The treatments were well tolerated.
      Using population pharmacokinetic modeling, a three-compartment model with zero
      order followed by first-order absorption and no lag time provided the best fit.
      The areas under the plasma concentration-time curve (AUC(0-infinity)) (28.7 and
      31.8 mg.h liter(-1) for pregnant and nonpregnant subjects, respectively) were
      consistent with the results of previous studies, but the estimated terminal
      elimination half-lives (78 and 77 h, respectively) were generally longer. The
      only significant relationship for a range of potential covariates, including
      malarial parasitemia, was with pregnancy, which accounted for an 86% increase in
      the volume of distribution of the central compartment relative to bioavailability
      without a significant change in the AUC(0-infinity). These data suggest that AZI
      can be combined with compounds with longer half-lives, such as SP, in combination
      IPTp without the need for dose adjustment.

PMID- 19858251
TI  - First report of the metallo-beta-lactamase SPM-1 in Europe.

PMID- 19858252
TI  - Factors influencing pharmacokinetics of prophylactic posaconazole in patients
      undergoing allogeneic stem cell transplantation.
AB  - The objectives of the present study were to elucidate the factors influencing the
      pharmacokinetics of prophylactically administered posaconazole in allogeneic
      hematopoietic stem cell transplant (SCT) recipients. Between May 2007 and
      November 2008, clinical data were obtained from all SCT recipients at the
      University Hospital of Cologne undergoing therapeutic drug monitoring (TDM) of
      serum prophylactic posaconazole concentrations. The posaconazole concentrations
      were determined by high-performance liquid chromatography. We developed a
      population pharmacokinetic model using nonlinear mixed-effect modeling (NONMEM).
      The list of covariates tested included age; body weight; body height; gender;
      posaconazole dose; race; coadministration of antineoplastic chemotherapy; day of
      stem cell transplantation; concomitant ranitidine, pantoprazole, cyclosporine, or
      tacrolimus administration; coincident fever; diarrhea; and plasma gamma
      glutamyltransferase activity. A total of 149 serum posaconazole concentrations
      from 32 patients were obtained. A one-compartment model with first-order
      absorption and elimination as the basic structural model appropriately described
      the data, with the apparent clearance being 75.8 liters/h (95% confidence
      interval [CI], 65.2 to 86.4 liters/h) and the apparent volume being distribution
      of 835 liters (95% CI, 559 to 1,111 liters). Among the covariates tested,
      significant effects were found for age (decrease in the volume of distribution of
      123 liters per year of age) and the presence of diarrhea (59% loss of
      bioavailability). A basis for prediction of the mean posaconazole concentrations
      in allogeneic SCT recipients with hematological malignancies is provided for a
      given dose. Corresponding adjustments of the starting dose according to the
      presence of diarrhea and according to age appear to be justified before TDM
      results are available.

PMID- 19858253
TI  - Identification of optimal renal dosage adjustments for traditional and extended
      infusion piperacillin-tazobactam dosing regimens in hospitalized patients.
AB  - This study examined the effect of various levels of renal impairment on the
      probability of achieving free drug concentrations that exceed the MIC for 50% of
      the dosing interval (50% fT > MIC) for traditional and extended-infusion
      piperacillin-tazobactam (TZP) dosing strategies. It also identified optimal renal
      dosage adjustments for traditional and extended-infusion dosing schemes that
      yielded probability of target attainment (PTA) and exposure profiles that were
      isometric to those of the parent regimens. Data from 105 patients were analyzed
      using the population pharmacokinetic modeling program BigNPAG. To assess the
      effect of creatinine clearance (CL(CR)) on overall clearance, TZP clearance was
      made proportional to the estimated CL(CR). A Monte Carlo simulation (9,999
      subjects) was performed for the traditional dosing scheme (4.5 g infused during
      30 min every 6 h) and the extended-infusion TZP dosing scheme (3.375 g infused
      during 4 h every 8 h). The fraction of simulated subjects who achieved 50% fT >
      MIC was calculated for the range of piperacillin MICs from 0.25 to 32 mg/liter
      and stratified by CL(CR). The traditional TZP regimen displayed the greatest
      variability in PTA across MIC values, especially for MIC values exceeding 4
      mg/liter, when stratified by CL(CR). In contrast, the PTA for the extended
      infusion TZP regimen exceeded >or=80% for MIC values of <or=8 mg/liter across all
      CL(CR) strata. All regimens were associated with suboptimal PTA for MIC values of
      >or=32 mg/liter irrespective of the CL(CR). The CL(CR) adjustments for
      traditional and extended-infusion TZP dosing regimens should be considered at a
      CL(CR) of <or=20 ml/min.

PMID- 19858254
TI  - Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance
      and virulence.
AB  - Respiratory infections caused by Klebsiella pneumoniae are characterized by high
      rates of mortality and morbidity. Management of these infections is often
      difficult, due to the high frequency of strains that are resistant to multiple
      antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of
      antimicrobial resistance in Gram-negative pathogens. In the present study, we
      investigated the role of the K. pneumoniae AcrRAB operon in antimicrobial
      resistance and virulence by using isogenic knockouts deficient in the AcrB
      component and the AcrR repressor, both derived from the virulent strain 52145R.
      We demonstrated that the AcrB knockout was more susceptible, not only to
      quinolones, but also to other antimicrobial agents, including beta-lactams, than
      the wild-type strain and the AcrR knockout. We further showed that the AcrB
      knockout was more susceptible to antimicrobial agents present in human
      bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild
      type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced
      capacity to cause pneumonia in a murine model, in contrast to the wild-type
      strain. The results of this study suggest that, in addition to contributing to
      the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel
      virulence factor required for K. pneumoniae to resist innate immune defense
      mechanisms of the lung, thus facilitating the onset of pneumonia.

PMID- 19858255
TI  - Pretreatment of epithelial cells with rifaximin alters bacterial attachment and
      internalization profiles.
AB  - Rifaximin is a poorly absorbed semisynthetic antibiotic derivative of rifampin
      licensed for use in the treatment of traveler's diarrhea. Rifaximin reduces the
      symptoms of enteric infection, often without pathogen eradication and with
      limited effects on intestinal flora. Epithelial cells (HEp-2 [laryngeal], HCT-8
      [ileocecal], A549 [lung], and HeLa [cervical]) were pretreated with rifaximin (or
      control antibiotics) prior to the addition of enteroaggregative Escherichia coli
      (EAEC). EAEC adherence was significantly reduced following rifaximin pretreatment
      compared to pretreatment with rifampin or doxycycline for three of the four cell
      lines tested. The rifaximin-mediated changes to epithelial cells were explored
      further by testing the attachment and internalization of either Bacillus
      anthracis or Shigella sonnei into A549 or HeLa cells, respectively. The
      attachment and internalization of B. anthracis were significantly reduced
      following rifaximin pretreatment. In contrast, neither the attachment nor the
      internalization of S. sonnei was affected by rifaximin pretreatment of HeLa
      cells, suggesting that rifaximin-mediated modulation of host cell physiology
      affected bacteria utilizing distinct attachment/internalization mechanisms
      differently. In addition, rifaximin pretreatment of HEp-2 cells led to reduced
      concentrations of inflammatory cytokines from uninfected cells. The study
      provides evidence that rifaximin-mediated changes in epithelial cell physiology
      are associated with changes in bacterial attachment/internalization and reduced
      inflammatory cytokine release.

PMID- 19858256
TI  - Pharmacometrics-based dose selection of levofloxacin as a treatment for
      postexposure inhalational anthrax in children.
AB  - Levofloxacin was recently (May 2008) approved by the U.S. Food and Drug
      Administration as a treatment for children following inhalational exposure to
      anthrax. Given that no clinical trials to assess the efficacy of a chosen dose
      was conducted, the basis for the dose recommendation was based upon
      pharmacometric analyses. The objective of this paper is to describe the basis of
      the chosen pediatric dose recommended for the label. Pharmacokinetic (PK) data
      from 90 pediatric patients receiving 7 mg/kg of body weight levofloxacin and two
      studies of 47 healthy adults receiving 500 and 750 mg/kg levofloxacin were used
      for the pharmacometric analyses. Body weight was found to be a significant
      covariate for levofloxacin clearance and the volume of distribution. Consistently
      with developmental physiology, clearance also was found to be reduced in
      pediatric patients under 2 years of age due to immature renal function. Different
      dosing regimens were simulated to match adult exposure (area under the
      concentration-time curve from 0 to 24 h at steady state, maximum concentration of
      drug in serum at steady state, and minimum concentration of drug in serum at
      steady state) following the approved adult dose of 500 mg once a day. The
      recommended dose of 8 mg/kg twice a day was found to match the exposure of the
      dose approved for adults in a manner that permitted confidence that this dose in
      children would achieve efficacy comparable to that of adults.

PMID- 19858257
TI  - A single mutation in enzyme I of the sugar phosphotransferase system confers
      penicillin tolerance to Streptococcus gordonii.
AB  - Tolerance is a poorly understood phenomenon that allows bacteria exposed to a
      bactericidal antibiotic to stop their growth and withstand drug-induced killing.
      This survival ability has been implicated in antibiotic treatment failures. Here,
      we describe a single nucleotide mutation (tol1) in a tolerant Streptococcus
      gordonii strain (Tol1) that is sufficient to provide tolerance in vitro and in
      vivo. It induces a proline-to-arginine substitution (P483R) in the
      homodimerization interface of enzyme I of the sugar phosphotransferase system,
      resulting in diminished sugar uptake. In vitro, the susceptible wild-type (WT)
      and Tol1 cultures lost 4.5 and 0.6 log(10) CFU/ml, respectively, after 24 h of
      penicillin exposure. The introduction of tol1 into the WT (WT P483R) conferred
      tolerance (a loss of 0.7 log(10) CFU/ml/24 h), whereas restitution of the parent
      sequence in Tol1 (Tol1 R483P) restored antibiotic susceptibility. Moreover,
      penicillin treatment of rats in an experimental model of endocarditis showed a
      complete inversion in the outcome, with a failure of therapy in rats infected
      with WT P483R and the complete disappearance of bacteria in animals infected with
      Tol1 R483P.

PMID- 19858258
TI  - An albumin-conjugated peptide exhibits potent anti-HIV activity and long in vivo
      half-life.
AB  - The clinical application of conventional peptide drugs often is limited by their
      short in vivo half-life and potential immunogenicity. Frequent injection presents
      challenges to the treatment of chronic diseases, such as HIV infection. We
      chemically modified a peptide HIV fusion inhibitor with 3-maleimidopropionic acid
      (MPA), which allows rapid and irreversible conjugation with serum albumin at a
      1:1 molar ratio. FB006M, with an MPA modification at the 13th amino acid, rapidly
      formed conjugate with albumin upon intravenous injection, and it exhibited a
      remarkably extended in vivo half-life. The albumin conjugate of FB006M displayed
      potent inhibitory activity against a number of laboratory and clinical isolates
      of HIV-1 in vitro and in vivo. No immunogenicity or antibody formation was
      detected after repeated dosing. The clinical application of FB006M may decrease
      the cost of treatment and improve treatment compliance and patient quality of
      life.

PMID- 19858259
TI  - Inhibition of B virus (Macacine herpesvirus 1) by conventional and experimental
      antiviral compounds.
AB  - B virus infection of humans results in high morbidity and mortality in as many as
      80% of identified cases. The main objective of this study was to conduct a
      comparative analysis of conventional and experimental antiviral drug
      susceptibilities of B virus isolates from multiple macaque species and
      zoonotically infected humans. We used a plaque reduction assay to establish the
      effective inhibitory doses of acyclovir, ganciclovir, and vidarabine, as well as
      those of a group of experimental nucleoside analogs with known anti-herpes
      simplex virus activity. Four of the experimental drugs tested were 10- to 100
      fold more potent inhibitors of B virus replication than conventional antiviral
      agents. Drug efficacies were similar for multiple B virus isolates tested, with
      variations within 2-fold of the median effective concentration (EC(50)) for each
      drug, and each EC(50) was considerably lower than those for B virus thymidine
      kinase (TK) mutants. We observed no differences in the viral TK amino acid
      sequence between B virus isolates from rhesus monkeys and those from human
      zoonoses. Differences in the TK protein sequence between cynomolgus and pigtail
      macaque B virus isolates did not affect drug sensitivity except in the case of
      one compound. Taken together, these data suggest that future B virus zoonoses
      will respond consistently to conventional antiviral treatment. Further, the
      considerably higher potency of FEAU (2'-fluoro-5-ethyl-Ara-U) than of
      conventional antiviral drugs argues for its compassionate use in advanced human B
      virus infections.

PMID- 19858261
TI  - Influence of tigecycline on expression of virulence factors in biofilm-associated
      cells of methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infections are complicated by
      the ability of the organism to grow in surface-adhered biofilms on a multitude of
      abiotic and biological surfaces. These multicellular communities are notoriously
      difficult to eradicate with antimicrobial therapy. Cells within the biofilm may
      be exposed to a sublethal concentration of the antimicrobial due to the metabolic
      and phenotypic diversity of the biofilm-associated cells or the protection
      offered by the biofilm structure. In the present study, the influence of a
      sublethal concentration of tigecycline on biofilms formed by an epidemic MRSA-16
      isolate was investigated by transcriptome analysis. In the presence of the drug,
      309 genes were upregulated and 213 genes were downregulated by more than twofold
      in comparison to the levels of gene regulation detected for the controls not
      grown in the presence of the drug. Microarray data were validated by real-time
      reverse transcription-PCR and phenotypic assays. Tigecycline altered the
      expression of a number of genes encoding proteins considered to be crucial for
      the virulence of S. aureus. These included the reduced expression of icaC, which
      is involved in polysaccharide intercellular adhesin production and biofilm
      development; the upregulation of fnbA, clfB, and cna, which encode adhesins which
      attach to human proteins; and the downregulation of the cap genes, which mediate
      the synthesis of the capsule polysaccharide. The expression of tst, which encodes
      toxic shock syndrome toxin 1 (TSST-1), was also significantly reduced; and an
      assay performed to quantify TSST-1 showed that the level of toxin production by
      cells treated with tigecycline decreased by 10-fold (P < 0.001) compared to the
      level of production by untreated control cells. This study suggests that
      tigecycline may reduce the expression of important virulence factors in S. aureus
      and supports further investigation to determine whether it could be a useful
      adjunct to therapy for the treatment of biofilm-mediated infections.

PMID- 19858260
TI  - Mapping simocyclinone D8 interaction with DNA gyrase: evidence for a new binding
      site on GyrB.
AB  - Simocyclinone D8, a coumarin derivative isolated from Streptomyces antibioticus
      Tu 6040, represents an interesting new antiproliferative agent. It was originally
      suggested that this drug recognizes the GyrA subunit and interferes with the
      gyrase catalytic cycle by preventing its binding to DNA. To further characterize
      the mode of action of this antibiotic, we investigated its binding to the
      reconstituted DNA gyrase (A(2)B(2)) as well as to its GyrA and GyrB subunits and
      the individual domains of these proteins, by performing protein melting and
      proteolytic digestion studies as well as inhibition assays. Two binding sites
      were identified, one (anticipated) in the N-terminal domain of GyrA (GyrA59) and
      the other (unexpected) at the C-terminal domain of GyrB (GyrB47). Stabilization
      of the A subunit appears to be considerably more effective than stabilization of
      the B subunit. Our data suggest that these two distinct sites could cooperate in
      the reconstituted enzyme.

PMID- 19858262
TI  - Phim46.1, the main Streptococcus pyogenes element carrying mef(A) and tet(O)
      genes.
AB  - Phim46.1, the recognized representative of the most common variant of mobile,
      prophage-associated genetic elements carrying resistance genes mef(A) (which
      confers efflux-mediated erythromycin resistance) and tet(O) (which confers
      tetracycline resistance) in Streptococcus pyogenes, was fully characterized.
      Sequencing of the Phim46.1 genome (55,172 bp) demonstrated a modular organization
      typical of tailed bacteriophages. Electron microscopic analysis of mitomycin
      induced Phim46.1 revealed phage particles with the distinctive icosahedral head
      and tail morphology of the Siphoviridae family. The chromosome integration site
      was within a 23S rRNA uracil methyltransferase gene. BLASTP analysis revealed
      that the proteins of Phim46.1 had high levels of amino acid sequence similarity
      to the amino acid sequences of proteins from other prophages, especially
      Phi10394.4 of S. pyogenes and lambdaSa04 of S. agalactiae. Phage DNA was present
      in the host cell both as a prophage and as free circular DNA. The lysogeny module
      appears to have been split due to the insertion of a segment containing tet(O)
      (from integrated conjugative element 2096-RD.2) and mef(A) (from a Tn1207.1-like
      transposon) into the unintegrated phage DNA. The phage attachment sequence lies
      in the region between tet(O) and mef(A) in the unintegrated form. Thus, whereas
      in this form tet(O) is approximately 5.5 kb upstream of mef(A), in the integrated
      form, tet(O), which lies close to the right end of the prophage, is approximately
      46.3 kb downstream of mef(A), which lies close to the left end of the prophage.

PMID- 19858263
TI  - Antifungal activity of colistin against mucorales species in vitro and in a
      murine model of Rhizopus oryzae pulmonary infection.
AB  - In immunosuppressed hosts, mucormycosis is a life-threatening infection with few
      treatment options. We studied the activity of colistin (polymyxin E) against
      Mucorales species in vitro and in a murine model of pulmonary Rhizopus oryzae
      infection. Colistin exhibited fungicidal activity in vitro against Mucorales
      spores and mycelia. At the colistin MIC, initial R. oryzae hyphal damage was
      followed by rapid regrowth; however, regrowth was prevented by combining colistin
      with a subinhibitory concentration of amphotericin B. Using electron microscopy
      and FM4-64 staining, we demonstrated that colistin disrupts R. oryzae cytoplasmic
      and vacuolar membranes, resulting in the leakage of intracellular contents. The
      prophylactic intranasal treatment of immunosuppressed mice with colistimethate
      significantly reduced the mortality rate and pulmonary fungal burden resulting
      from inhalational challenge with R. oryzae spores, whereas intraperitoneal
      colistimethate treatment had no effect. We conclude that colistin has modest in
      vitro and in vivo fungicidal activity against Mucorales spp. Further studies are
      warranted to assess the use of this drug in the prevention and treatment of
      mucormycosis.

PMID- 19858264
TI  - Dispatch from the medical front: Reflections on council.

PMID- 19858268
TI  - H1N1-related SIRS?

PMID- 19858270
TI  - Acetaminophen and asthma.

PMID- 19858271
TI  - Who is the bad apple?

PMID- 19858272
TI  - Bedbugs and health.

PMID- 19858273
TI  - Spain and swine flu.

PMID- 19858274
TI  - Creative Works: The gentle ask.

PMID- 19858275
TI  - Poetry: They were beautiful once.

PMID- 19858277
TI  - Illicit tobacco: Governments continue to blow smoke.

PMID- 19858278
TI  - Highlights from the 9th International Family Nursing Conference.

PMID- 19858279
TI  - Distinguished contribution to Family Nursing Award 2009: Marcia Van Riper, RN,
      PhD.

PMID- 19858280
TI  - Families' and nurses' responses to the "One Question Question": reflections for
      clinical practice, education, and research in family nursing.
AB  - The "One Question Question," first coined by Dr. Lorraine M. Wright in 1989, is
      an interventive question designed to elicit family members' most pressing needs
      or concerns within the context of a therapeutic conversation. In this article,
      two clinical projects analyzed the responses to this unique interventive
      question. The first project analyzed the responses of 192 family members
      experiencing illness who were asked the question in the context of a therapeutic
      conversation; families focused on their need to deal with the impact of the
      illness on the family. The second project examined responses of 297 nurses who
      were asked the question prior to a 1-week Family Systems Nursing training
      program; nurses wanted to know how to deal with conflictual relationships between
      families and health care professionals and how to offer families time-efficient
      interventions. The responses from both groups, which were markedly different,
      triggered reflections about teaching, research, and practice in family nursing.

PMID- 19858281
TI  - Outcomes following an early parenting center residential parenting program.
AB  - Outcomes for maternal well-being and behavior as well as difficult child behavior
      following participation in a 5-day early parenting center residential parenting
      program were explored. Participants were 44 mothers and their children, the
      majority presenting with child sleeping difficulties. Data were collected at four
      stages: intake (2-4 weeks prior to the program), the first day of the program,
      the last day of the program, and 4 weeks after the program. Measures included
      questionnaires, monitoring sheets, and videotaped observations of parent- child
      interactions. Improvements were seen in mothers' behavior during parent-child
      interaction over the week they attended the program. Maternal symptoms of
      depression, anxiety, and stress were lower after the program. The perceived
      frequency and seriousness of maternal reported difficult child behavior decreased
      over the measurement period, and 52% of parents had achieved 80% or more of their
      behavioral goal for their children. Implications for future research in early
      parenting centers are discussed.

PMID- 19858283
TI  - Estimating breeding values with molecular relatedness and reconstructed pedigrees
      in natural mating populations of common sole, Solea solea.
AB  - Captive populations where natural mating in groups is used to obtain offspring
      typically yield unbalanced population structures with highly skewed parental
      contributions and unknown pedigrees. Consequently, for genetic parameter
      estimation, relationships need to be reconstructed or estimated using DNA marker
      data. With missing parents and natural mating groups, commonly used pedigree
      reconstruction methods are not accurate and lead to loss of data. Relatedness
      estimators, however, infer relationships between all animals sampled. In this
      study, we compared a pedigree relatedness method and a relatedness estimator
      ("molecular relatedness") method using accuracy of estimated breeding values. A
      commercial data set of common sole, Solea solea, with 51 parents and 1953
      offspring ("full data set") was used. Due to missing parents, for 1338 offspring,
      a pedigree could be reconstructed with 10 microsatellite markers ("reduced data
      set").

PMID- 19858284
TI  - Defining and mapping mammalian coat pattern genes: multiple genomic regions
      implicated in domestic cat stripes and spots.
AB  - Mammalian coat patterns (e.g., spots, stripes) are hypothesized to play important
      roles in camouflage and other relevant processes, yet the genetic and
      developmental bases for these phenotypes are completely unknown. The domestic
      cat, with its diversity of coat patterns, is an excellent model organism to
      investigate these phenomena. We have established three independent pedigrees to
      map the four recognized pattern variants classically considered to be specified
      by a single locus, Tabby; in order of dominance, these are the unpatterned agouti
      form called "Abyssinian" or "ticked" (T(a)), followed by Spotted (T(s)), Mackerel
      (T(M)), and Blotched (t(b)). We demonstrate that at least three different loci
      control the coat markings of the domestic cat. One locus, responsible for the
      Abyssinian form (herein termed the Ticked locus), maps to an approximately 3.8-Mb
      region on cat chromosome B1. A second locus controls the Tabby alleles T(M) and
      t(b), and maps to an approximately 5-Mb genomic region on cat chromosome A1. One
      or more additional loci act as modifiers and create a spotted coat by altering
      mackerel stripes. On the basis of our results and associated observations, we
      hypothesize that mammalian patterned coats are formed by two distinct processes:
      a spatially oriented developmental mechanism that lays down a species-specific
      pattern of skin cell differentiation and a pigmentation-oriented mechanism that
      uses information from the preestablished pattern to regulate the synthesis of
      melanin profiles.

PMID- 19858285
TI  - Evolution at a high imposed mutation rate: adaptation obscures the load in phage
      T7.
AB  - Evolution at high mutation rates is expected to reduce population fitness
      deterministically by the accumulation of deleterious mutations. A high enough
      rate should even cause extinction (lethal mutagenesis), a principle motivating
      the clinical use of mutagenic drugs to treat viral infections. The impact of a
      high mutation rate on long-term viral fitness was tested here. A large population
      of the DNA bacteriophage T7 was grown with a mutagen, producing a genomic rate of
      4 nonlethal mutations per generation, two to three orders of magnitude above the
      baseline rate. Fitness-viral growth rate in the mutagenic environment-was
      predicted to decline substantially; after 200 generations, fitness had increased,
      rejecting the model. A high mutation load was nonetheless evident from (i) many
      low- to moderate-frequency mutations in the population (averaging 245 per genome)
      and (ii) an 80% drop in average burst size. Twenty-eight mutations reached high
      frequency and were thus presumably adaptive, clustered mostly in DNA metabolism
      genes, chiefly DNA polymerase. Yet blocking DNA polymerase evolution failed to
      yield a fitness decrease after 100 generations. Although mutagenic drugs have
      caused viral extinction in vitro under some conditions, this study is the first
      to match theory and fitness evolution at a high mutation rate. Failure of the
      theory challenges the quantitative basis of lethal mutagenesis and highlights the
      potential for adaptive evolution at high mutation rates.

PMID- 19858286
TI  - Flipping DNA to generate and regulate microbial consortia.
AB  - Communities of interdependent microbes, found in diverse natural contexts, have
      recently attracted the attention of bioengineers. Such consortia have potential
      applications in biosynthesis, with metabolic tasks distributed over several
      phenotypes, and in live-cell microbicide therapies where phenotypic diversity
      might aid in immune evasion. Here we investigate one route to generate synthetic
      microbial consortia and to regulate their phenotypic diversity, through
      programmed genetic interconversions. In our theoretical model, genotypes involve
      ordered combinations of DNA elements representing promoters, protein-coding
      genes, and transcription terminators; genotypic interconversions are driven by a
      recombinase enzyme that inverts DNA segments; and selectable phenotypes
      correspond to distinct patterns of gene expression. We analyze the microbial
      population as it evolves along a graph whose nodes are distinct genotypes and
      whose edges are interconversions. We show that the steady-state proportion of
      each genotype depends on its own growth advantage, as well as on its connectivity
      to other genotypes. Multiple phenotypes with identical or distinct growth rates
      can be indefinitely maintained in the population, while their proportion can be
      regulated by varying the rate of DNA flipping. Recombinase-based synthetic
      constructs have already been implemented; the graph-theoretic framework developed
      here will be useful in adapting them to generate microbial consortia.

PMID- 19858287
TI  - Circadian amplitude of cryptochrome 1 is modulated by mRNA stability regulation
      via cytoplasmic hnRNP D oscillation.
AB  - The mammalian circadian rhythm is observed not only at the suprachiasmatic
      nucleus, a master pacemaker, but also throughout the peripheral tissues. Its
      conserved molecular basis has been thought to consist of intracellular
      transcriptional feedback loops of key clock genes. However, little is known about
      posttranscriptional regulation of these genes. In the present study, we
      investigated the role of the 3'-untranslated region (3'UTR) of the mouse
      cryptochrome 1 (mcry1) gene at the posttranscriptional level. Mature mcry1 mRNA
      has a 610-nucleotide 3'UTR and mediates its own degradation. The middle part of
      the 3'UTR contains a destabilizing cis-acting element. The deletion of this
      element led to a dramatic increase in mRNA stability, and heterogeneous nuclear
      ribonucleoprotein D (hnRNP D) was identified as an RNA binding protein
      responsible for this effect. Cytoplasmic hnRNP D levels displayed a pattern that
      was reciprocal to the mcry1 oscillation. Knockdown of hnRNP D stabilized mcry1
      mRNA and resulted in enhancement of the oscillation amplitude and a slight delay
      of the phase. Our results suggest that hnRNP D plays a role as a fine regulator
      contributing to the mcry1 mRNA turnover rate and the modulation of circadian
      rhythm.

PMID- 19858288
TI  - Tom20 mediates localization of mRNAs to mitochondria in a translation-dependent
      manner.
AB  - mRNAs encoding mitochondrial proteins are enriched in the vicinity of
      mitochondria, presumably to facilitate protein transport. A possible mechanism
      for enrichment may involve interaction of the translocase of the mitochondrial
      outer membrane (TOM) complex with the precursor protein while it is translated,
      thereby leading to association of polysomal mRNAs with mitochondria. To test this
      hypothesis, we isolated mitochondrial fractions from yeast cells lacking the
      major import receptor, Tom20, and compared their mRNA repertoire to that of wild
      type cells by DNA microarrays. Most mRNAs encoding mitochondrial proteins were
      less associated with mitochondria, yet the extent of decrease varied among genes.
      Analysis of several mRNAs revealed that optimal association of Tom20 target mRNAs
      requires both translating ribosomes and features within the encoded mitochondrial
      targeting signal. Recently, Puf3p was implicated in the association of mRNAs with
      mitochondria through interaction with untranslated regions. We therefore
      constructed a tom20 Delta puf3 Delta double-knockout strain, which demonstrated
      growth defects under conditions where fully functional mitochondria are required.
      Mislocalization effects for few tested mRNAs appeared stronger in the double
      knockout than in the tom20 Delta strain. Taken together, our data reveal a large
      scale mRNA association mode that involves interaction of Tom20p with the
      translated mitochondrial targeting sequence and may be assisted by Puf3p.

PMID- 19858289
TI  - Mss51 and Ssc1 facilitate translational regulation of cytochrome c oxidase
      biogenesis.
AB  - The intricate biogenesis of multimeric organellar enzymes of dual genetic origin
      entails several levels of regulation. In Saccharomyces cerevisiae, mitochondrial
      cytochrome c oxidase (COX) assembly is regulated translationally. Synthesis of
      subunit 1 (Cox1) is contingent on the availability of its assembly partners,
      thereby acting as a negative feedback loop that coordinates COX1 mRNA translation
      with Cox1 utilization during COX assembly. The COX1 mRNA-specific translational
      activator Mss51 plays a fundamental role in this process. Here, we report that
      Mss51 successively interacts with the COX1 mRNA translational apparatus, newly
      synthesized Cox1, and other COX assembly factors during Cox1 maturation/assembly.
      Notably, the mitochondrial Hsp70 chaperone Ssc1 is shown to be an Mss51 partner
      throughout its metabolic cycle. We conclude that Ssc1, by interacting with Mss51
      and Mss51-containing complexes, plays a critical role in Cox1 biogenesis, COX
      assembly, and the translational regulation of these processes.

PMID- 19858290
TI  - A bifunctional regulatory element in human somatic Wee1 mediates cyclin A/Cdk2
      binding and Crm1-dependent nuclear export.
AB  - Sophisticated models for the regulation of mitotic entry are lacking for human
      cells. Inactivating human cyclin A/Cdk2 complexes through diverse approaches
      delays mitotic entry and promotes inhibitory phosphorylation of Cdk1 on tyrosine
      15, a modification performed by Wee1. We show here that cyclin A/Cdk2 complexes
      physically associate with Wee1 in U2OS cells. Mutation of four conserved RXL
      cyclin A/Cdk binding motifs (RXL1 to RXL4) in Wee1 diminished stable binding.
      RXL1 resides within a large regulatory region of Wee1 that is predicted to be
      intrinsically disordered (residues 1 to 292). Near RXL1 is T239, a site of
      inhibitory Cdk phosphorylation in Xenopus Wee1 proteins. We found that T239 is
      phosphorylated in human Wee1 and that this phosphorylation was reduced in an RXL1
      mutant. RXL1 and T239 mutants each mediated greater Cdk phosphorylation and
      G(2)/M inhibition than the wild type, suggesting that cyclin A/Cdk complexes
      inhibit human Wee1 through these sites. The RXL1 mutant uniquely also displayed
      increased nuclear localization. RXL1 is embedded within sequences homologous to
      Crm1-dependent nuclear export signals (NESs). Coimmunoprecipitation showed that
      Crm1 associated with Wee1. Moreover, treatment with the Crm1 inhibitor leptomycin
      B or independent mutation of the potential NES (NESm) abolished Wee1 nuclear
      export. Export was also reduced by Cdk inhibition or cyclin A RNA interference,
      suggesting that cyclin A/Cdk complexes contribute to Wee1 export. Somewhat
      surprisingly, NESm did not display increased G(2)/M inhibition. Thus, nuclear
      export of Wee1 is not essential for mitotic entry though an important functional
      role remains likely. These studies identify a novel bifunctional regulatory
      element in Wee1 that mediates cyclin A/Cdk2 association and nuclear export.

PMID- 19858291
TI  - Friend of Prmt1, a novel chromatin target of protein arginine methyltransferases.
AB  - We describe the isolation and characterization of Friend of Prmt1 (Fop), a novel
      chromatin target of protein arginine methyltransferases. Human Fop is encoded by
      C1orf77, a gene of previously unknown function. We show that Fop is tightly
      associated with chromatin, and that it is modified by both asymmetric and
      symmetric arginine methylation in vivo. Furthermore, Fop plays an important role
      in the ligand-dependent activation of estrogen receptor target genes, including
      TFF1 (pS2). Fop depletion results in an almost complete block of estradiol
      induced promoter occupancy by the estrogen receptor. Our data indicate that Fop
      recruitment to the promoter is an early critical event in the activation of
      estradiol-dependent transcription.

PMID- 19858292
TI  - Activation of the S-phase checkpoint inhibits degradation of the F-box protein
      Dia2.
AB  - A stable genome is critical to cell viability and proliferation. During DNA
      replication, the S-phase checkpoint pathway responds to replication stress. In
      budding yeast, the chromatin-bound F-box protein Dia2 is required to maintain
      genomic stability and may help replication complexes overcome sites of damaged
      DNA and natural fragile regions. SCF (Skp1/Cul1/F-box protein) complexes are
      modular ubiquitin ligases. We show here that Dia2 is itself targeted for
      ubiquitin-mediated proteolysis and that activation of the S-phase checkpoint
      pathway inhibits Dia2 protein degradation. S-phase checkpoint mutants fail to
      stabilize Dia2 in response to replication stress. Deletion of DIA2 from these
      checkpoint mutants exacerbates their sensitivity to hydroxyurea, suggesting that
      stabilization of Dia2 contributes to the replication stress response. Unlike the
      case for other F-box proteins, deletion of the F-box domain in Dia2 does not
      stabilize the protein. Rather, an N-terminal domain that is also required for
      nuclear localization is necessary for degradation. When a strong nuclear
      localization signal (NLS) is added to dia2 mutants lacking this domain, the Dia2
      protein is both stable and nuclear. Together, our results suggest that Dia2
      protein turnover does not involve an autocatalytic mechanism and that Dia2
      proteolysis is inhibited by activation of the replication stress response.

PMID- 19858293
TI  - Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha
      enhances hypoxic gene expression and tumor growth.
AB  - The hypoxia-inducible transcription factors (HIFs) directly and indirectly
      mediate cellular adaptation to reduced oxygen tensions. Recent studies have shown
      that the histone demethylase genes JMJD1A, JMJD2B, and JARID1B are HIF targets,
      suggesting that HIFs indirectly influence gene expression at the level of histone
      methylation under hypoxia. In this study, we identify a subset of hypoxia
      inducible genes that are dependent on JMJD1A in both renal cell and colon
      carcinoma cell lines. JMJD1A regulates the expression of adrenomedullin (ADM) and
      growth and differentiation factor 15 (GDF15) under hypoxia by decreasing promoter
      histone methylation. In addition, we demonstrate that loss of JMJD1A is
      sufficient to reduce tumor growth in vivo, demonstrating that histone
      demethylation plays a significant role in modulating growth within the tumor
      microenvironment. Thus, hypoxic regulation of JMJD1A acts as a signal amplifier
      to facilitate hypoxic gene expression, ultimately enhancing tumor growth.

PMID- 19858294
TI  - The stability of cytadherence proteins in Mycoplasma pneumoniae requires activity
      of the protein kinase PrkC.
AB  - Mycoplasma pneumoniae belongs to the mollicutes, a group of bacteria that have
      strongly reduced genomes but that are nevertheless capable of independent life.
      With only three transcription factors, the regulatory features of these bacteria
      are very limited. Thus, posttranslational regulation might be important for M.
      pneumoniae. In addition to the highly specific HPr kinase, the M. pneumoniae prkC
      gene encodes the serine/threonine protein kinase C. In order to study the
      function(s) of this kinase, we isolated an M. pneumoniae mutant affected in PrkC.
      This mutation resulted in nonadherent growth and loss of cytotoxicity.
      Examination of the phosphorylation profile of the prkC mutant suggested that
      phosphorylation of cytadherence proteins was affected by the loss of this kinase.
      In contrast, inactivation of the prpC gene affecting the protein phosphatase that
      antagonizes PrkC-dependent phosphorylation resulted in more intensive
      phosphorylation of the cytadherence proteins HMW1 and HMW3 of the major adhesin
      P1 and of the surface protein MPN474. Moreover, loss of PrkC affects not only the
      phosphorylation state of the cytadherence proteins but also their intracellular
      accumulation. However, the expression of the corresponding genes was not affected
      by PrkC, suggesting that PrkC-dependent phosphorylation results in stabilization
      of the cytadherence proteins. The HMW proteins and P1 are part of the so-called
      terminal organelle of M. pneumoniae that is involved in gliding motility, cell
      division, and adhesion to host epithelial tissues. Our observations suggest that
      the posttranslational modification of cytadherence proteins by PrkC is essential
      for the development and function of the M. pneumoniae terminal organelle.

PMID- 19858295
TI  - Major surface protease of trypanosomatids: one size fits all?
AB  - Major surface protease (MSP or GP63) is the most abundant glycoprotein localized
      to the plasma membrane of Leishmania promastigotes. MSP plays several important
      roles in the pathogenesis of leishmaniasis, including but not limited to (i)
      evasion of complement-mediated lysis, (ii) facilitation of macrophage (Mo)
      phagocytosis of promastigotes, (iii) interaction with the extracellular matrix,
      (iv) inhibition of natural killer cellular functions, (v) resistance to
      antimicrobial peptide killing, (vi) degradation of Mo and fibroblast cytosolic
      proteins, and (vii) promotion of survival of intracellular amastigotes. MSP
      homologues have been found in all other trypanosomatids studied to date including
      heteroxenous members of Trypanosoma cruzi, the extracellular Trypanosoma brucei,
      unusual intraerythrocytic Endotrypanum spp., phytoparasitic Phytomonas spp., and
      numerous monoxenous species. These proteins are likely to perform roles different
      from those described for Leishmania spp. Multiple MSPs in individual cells may
      play distinct roles at some time points in trypanosomatid life cycles and
      collaborative or redundant roles at others. The cellular locations and the
      extracellular release of MSPs are also discussed in connection with MSP functions
      in leishmanial promastigotes.

PMID- 19858296
TI  - Development of immunoglobulin M memory to both a T-cell-independent and a T-cell
      dependent antigen following infection with Vibrio cholerae O1 in Bangladesh.
AB  - Vibrio cholerae O1 can cause severe watery diarrhea that can be life-threatening
      without treatment. Infection results in long-lasting protection against
      subsequent disease. Development of memory B cells of the immunoglobulin G (IgG)
      and IgA isotypes to V. cholerae O1 antigens, including serotype-specific
      lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB), after cholera
      infection has been demonstrated. Memory B cells of the IgM isotype may play a
      role in long-term protection, particularly against T-cell-independent antigens,
      but IgM memory has not been studied in V. cholerae O1 infection. Therefore, we
      assayed acute- and convalescent-phase blood samples from cholera patients for the
      presence of memory B cells that produce cholera antigen-specific IgM antibody
      upon polyclonal stimulation in in vitro culture. We also examined the development
      of serological and antibody-secreting cell responses following infection.
      Subjects developed significant IgM memory responses by day 30 after infection,
      both to the T-cell-independent antigen LPS and to the T-cell-dependent antigen
      CTB. No significant corresponding elevations in plasma IgM antibodies or
      circulating IgM antibody-secreting cells to CTB were detected. In 17 subjects
      followed to day 90 after infection, significant persistence of elevated IgM
      memory responses was not observed. The IgM memory response to CTB was negatively
      correlated with the IgG plasma antibody response to CTB, and there was a trend
      toward negative correlation between the IgM memory and IgA plasma antibody
      responses to LPS. We did not observe an association between the IgM memory
      response to LPS and the vibriocidal titer.

PMID- 19858297
TI  - A monoclonal immunoglobulin G antibody directed against an immunodominant linear
      epitope on the ricin A chain confers systemic and mucosal immunity to ricin.
AB  - Due to the potential use of ricin and other fast-acting toxins as agents of
      bioterrorism, there is an urgent need for the development of safe and effective
      antitoxin vaccines. A candidate ricin subunit vaccine (RiVax) consisting of a
      recombinant attenuated enzymatic A chain (RTA) has been shown to elicit
      protective antitoxin antibodies in mice and rabbits and is currently being tested
      in phase I human clinical trials. However, evaluation of the efficacy of this
      vaccine for humans is difficult for a number of reasons, including the fact that
      the key neutralizing B-cell epitopes on RTA have not been fully defined.
      Castelletti and colleagues (Clin. Exp. Immunol. 136:365-372, 2004) recently
      identified a linear epitope on RTA, spanning residues L161 to I175, as a primary
      target of serum antibodies derived from humans who had been treated with ricin
      immunotoxin. While affinity-purified polyclonal IgG antibodies against this
      region of RTA were capable of neutralizing ricin in vitro, their capacity to
      confer protection against ricin challenge in vivo was not determined. In this
      report, we describe the production and characterization of GD12, a murine
      monoclonal IgG1 antibody specifically directed against residues 163 to 174
      (TLARSFIICIQM) of RTA. GD12 bound ricin holotoxin with high affinity (K(D)
      [dissociation constant], 2.9 x 10(-9) M) and neutralized it with a 50% inhibitory
      concentration of approximately 0.25 microg/ml, as determined by a Vero cell-based
      cytotoxicity assay. Passive administration of GD12 was sufficient to protect
      BALB/c mice against intraperitoneal and intragastric ricin challenges. These data
      are important in terms of vaccine development, since they firmly establish that
      preexisting serum antibodies directed against residues 161 to 175 on RTA are
      sufficient to confer both systemic and mucosal immunity to ricin. The potential
      of GD12 to serve as a therapeutic following ricin challenge was not explored in
      this study.

PMID- 19858298
TI  - Systematic analysis of the SsrAB virulon of Salmonella enterica.
AB  - Intracellular Salmonella enterica serovar Typhimurium deploys the Salmonella
      pathogenicity island 2 (SPI2)-encoded type III secretion system (T3SS) to modify
      host cell functions and accomplish intracellular replication. This virulence
      function is controlled by the two-component system SsrAB that regulates the
      expression of several operons in SPI2 and, in addition, a large number of genes
      for non-SPI2-encoded effector proteins. Here, we analyzed the relative expression
      levels of members of the SsrAB virulon. We used a novel reporter fusion strategy
      for single-copy chromosomal fusions, all done in an identical manner in order to
      enable direct quantitative comparison. We observed very high expression levels
      for sseJ and sifA; high expression levels for ssaG, steC, sseL, and sopD2;
      moderate expression levels for ssaB, sseA, sseG, sifB, pipB2, and sspH1; and low
      expression levels for sspH2, sseI, slrP, sseK1, sseK2, pipB, and gogB. The
      expression of the SsrAB virulon was highly dependent on the function of SsrB but
      also required EnvR/OmpZ. Deletion of PhoP, part of the global regulatory system
      PhoPQ, resulted in highly delayed expression of the SsrAB virulon under in vitro
      conditions; however, maximal expression was similar to that in a wild-type
      background. The expression levels of SsrAB-dependent genes in intracellular
      bacteria were in good agreement with in vitro analyses. We provide here a
      comprehensive and fully comparable analysis of the expression of genes in the
      SsrAB virulon. This information will be of interest for the selection of in vivo
      activated promoters, for example, for rational design of recombinant vaccines.

PMID- 19858299
TI  - An orally applicable Shiga toxin neutralizer functions in the intestine to
      inhibit the intracellular transport of the toxin.
AB  - Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing
      Escherichia coli (STEC), which causes gastrointestinal diseases and sometimes
      fatal systemic complications. Recently, we developed an oral Stx2 inhibitor known
      as Ac-PPP-tet that exhibits remarkable therapeutic potency in an STEC infection
      model. However, the precise mechanism underlying the in vivo therapeutic effects
      of Ac-PPP-tet is unknown. Here, we found that Ac-PPP-tet completely inhibited
      fluid accumulation in the rabbit ileum caused by the direct injection of Stx2.
      Interestingly, Ac-PPP-tet accumulated in the ileal epithelial cells only through
      its formation of a complex with Stx2. The formation of Ac-PPP-tet-Stx2 complexes
      in cultured epithelial cells blocked the intracellular transport of Stx2 from the
      Golgi apparatus to the endoplasmic reticulum, a process that is essential for
      Stx2 cytotoxicity. Thus, Ac-PPP-tet is the first Stx neutralizer that functions
      in the intestine by altering the intracellular transport of Stx2 in epithelial
      cells.

PMID- 19858300
TI  - Characterization of virulence plasmid diversity among Clostridium perfringens
      type B isolates.
AB  - The important veterinary pathogen Clostridium perfringens type B is unique for
      producing the two most lethal C. perfringens toxins, i.e., epsilon-toxin and beta
      toxin. Our recent study (K. Miyamoto, J. Li, S. Sayeed, S. Akimoto, and B. A.
      McClane, J. Bacteriol. 190:7178-7188, 2008) showed that most, if not all, type B
      isolates carry a 65-kb epsilon-toxin-encoding plasmid. However, this epsilon
      toxin plasmid did not possess the cpb gene encoding beta-toxin, suggesting that
      type B isolates carry at least one additional virulence plasmid. Therefore, the
      current study used Southern blotting of pulsed-field gels to localize the cpb
      gene to approximately 90-kb plasmids in most type B isolates, although a few
      isolates carried a approximately 65-kb cpb plasmid distinct from their etx
      plasmid. Overlapping PCR analysis then showed that the gene encoding the recently
      discovered TpeL toxin is located approximately 3 kb downstream of the plasmid
      borne cpb gene. As shown earlier for their epsilon-toxin-encoding plasmids, the
      beta-toxin-encoding plasmids of type B isolates were found to carry a tcp locus,
      suggesting that they are conjugative. Additionally, IS1151-like sequences were
      identified upstream of the cpb gene in type B isolates. These IS1151-like
      sequences may mobilize the cpb gene based upon detection of possible cpb
      containing circular transposition intermediates. Most type B isolates also
      possessed a third virulence plasmid that carries genes encoding urease and lambda
      toxin. Collectively, these findings suggest that type B isolates are among the
      most plasmid dependent of all C. perfringens isolates for virulence, as they
      usually carry three potential virulence plasmids.

PMID- 19858301
TI  - Production of reactive oxygen species is turned on and rapidly shut down in
      epithelial cells infected with Chlamydia trachomatis.
AB  - Reactive oxygen species (ROS) are many-faceted compounds involved in cell defense
      against pathogens, as well as in cell signaling. Their involvement in the
      response to infection in epithelial cells remains poorly documented. Here, we
      investigated the production of ROS during infection with Chlamydia trachomatis, a
      strict intracellular pathogen, in HeLa cells. C. trachomatis induced a transient
      increase in the ROS level within a few hours, followed by a return to basal level
      9 hours after infection. At this time point, the host enzyme dedicated to ROS
      production, NADPH oxidase, could no longer be activated by external stimuli, such
      as interleukin-1beta. In addition, Rac, a regulatory subunit of the NADPH oxidase
      complex, was relocated to the membrane of the compartment in which the bacteria
      develop, the inclusion, while other subunits were not. Altogether, these results
      indicate that C. trachomatis infection elicits the production of ROS and that the
      bacteria rapidly target the activity of NADPH oxidase to shut it down. Prevention
      of ROS production at the onset of the bacterial developmental cycle might delay
      the host response to infection.

PMID- 19858302
TI  - Impairment of gamma interferon signaling in human neutrophils infected with
      Anaplasma phagocytophilum.
AB  - Anaplasma phagocytophilum, the causative agent of tick-borne human granulocytic
      anaplasmosis (HGA), is an intracellular bacterium which survives and multiplies
      inside polymorphonuclear neutrophil granulocytes (PMN). Increased bacterial
      burden in gamma interferon (IFN-gamma)-deficient mice suggested a major role of
      IFN-gamma in the control of A. phagocytophilum. Here we investigated whether
      infection of human PMN with A. phagocytophilum impairs IFN-gamma signaling thus
      facilitating intracellular survival of the bacterium. The secretion of the IFN
      gamma-inducible chemokines IP-10/CXCL10 and MIG/CXCL9 was markedly inhibited in
      infected neutrophils. Molecular analyses revealed that, compared to uninfected
      PMN, A. phagocytophilum decreased the expression of the IFN-gamma receptor alpha
      chain CD119, diminished the IFN-gamma-induced phosphorylation of STAT1, and
      enhanced the expression of SOCS1 and SOCS3 in PMN. Since IFN-gamma activates
      various antibacterial effector mechanisms of PMN, the impaired IFN-gamma
      signaling in infected cells likely contributes to the survival of A.
      phagocytophilum inside PMN and to HGA disease development.

PMID- 19858303
TI  - Functional characterization of Borrelia spielmanii outer surface proteins that
      interact with distinct members of the human factor H protein family and with
      plasminogen.
AB  - Acquisition of complement regulator factor H (CFH) and factor H-like protein 1
      (CFHL1) from human serum enables Borrelia spielmanii, one of the etiological
      agents of Lyme disease, to evade complement-mediated killing by the human host.
      Up to three distinct complement regulator-acquiring surface proteins (CRASPs) may
      be expressed by serum-resistant B. spielmanii, each exhibiting an affinity for
      CFH and/or CFHL1. Here, we describe the functional characterization of the 15-kDa
      CRASPs of B. spielmanii, members of the polymorphic Erp (OspE/F-related) protein
      family, that bind two distinct host complement regulators, CFH and factor H
      related protein 1 (CFHR1), but not CFHL1. CFH bound to the B. spielmanii CRASPs
      maintained cofactor activity for factor I-mediated C3b inactivation. Three
      naturally occurring alleles of this protein bound CFH and CFHR1 while a fourth
      natural allele could not. Comparative sequence analysis of these protein alleles
      identified a single amino acid, histidine-79, as playing a significant role in
      CFH/CFHR1 binding, with substitution by an arginine completely abrogating ligand
      binding. The mutation of His-79 to Arg did not inhibit binding of plasminogen,
      another known ligand of this group of borrelial outer-surface proteins.

PMID- 19858304
TI  - Acid phosphatases do not contribute to the pathogenesis of type A Francisella
      tularensis.
AB  - The intracellular pathogen Francisella tularensis is the causative agent of
      tularemia, a zoonosis that can affect humans with potentially lethal
      consequences. Essential to Francisella virulence is its ability to survive and
      proliferate within phagocytes through phagosomal escape and cytosolic
      replication. Francisella spp. encode a variety of acid phosphatases, whose roles
      in phagosomal escape and virulence have been documented yet remain controversial.
      Here we have examined in the highly virulent (type A) F. tularensis strain Schu
      S4 the pathogenic roles of three distinct acid phosphatases, AcpA, AcpB, and
      AcpC, that are most conserved between Francisella subspecies. Neither the
      deletion of acpA nor the combination of acpA, acpB, and acpC deletions affected
      the phagosomal escape or cytosolic growth of Schu S4 in murine and human
      macrophages, despite decreases in acid phosphatase activities by as much as 95%.
      Furthermore, none of these mutants were affected in their ability to cause
      lethality in mice upon intranasal inoculation. Hence, the acid phosphatases AcpA,
      AcpB, and AcpC do not contribute to intracellular pathogenesis and do not play a
      major role in the virulence of type A Francisella strains.

PMID- 19858305
TI  - Division of the Salmonella-containing vacuole and depletion of acidic lysosomes
      in Salmonella-infected host cells are novel strategies of Salmonella enterica to
      avoid lysosomes.
AB  - Salmonella has evolved several strategies to counteract intracellular
      microbicidal agents like reactive oxygen and nitrogen species. However, it is not
      yet clear how Salmonella escapes lysosomal degradation. Some studies have
      demonstrated that Salmonella can inhibit phagolysosomal fusion, whereas other
      reports have shown that the Salmonella-containing vacuole (SCV) fuses/interacts
      with lysosomes. Here, we have addressed this issue from a different perspective
      by investigating if the infected host cell has a sufficient quantity of lysosomes
      to target Salmonella. Our results suggest that SCVs divide along with Salmonella,
      resulting in a single bacterium per SCV. As a consequence, the SCV load per cell
      increases with the division of Salmonella inside the host cell. This demands more
      investment from the host cell to counteract Salmonella. Interestingly, we
      observed that Salmonella infection decreases the number of acidic lysosomes
      inside the host cell both in vitro and in vivo. These events potentially result
      in a condition in which an infected cell is left with insufficient acidic
      lysosomes to target the increasing number of SCVs, which favors the survival and
      proliferation of Salmonella inside the host cell.

PMID- 19858306
TI  - Prime-boost immunization with adenoviral and modified vaccinia virus Ankara
      vectors enhances the durability and polyfunctionality of protective malaria CD8+
      T-cell responses.
AB  - Protection against liver-stage malaria relies on the induction of high
      frequencies of antigen-specific CD8+ T cells. We have previously reported high
      protective levels against mouse malaria, albeit short-lived, by a single
      vaccination with adenoviral vectors coding for a liver-stage antigen (ME.TRAP).
      Here, we report that prime-boost regimens using modified vaccinia virus Ankara
      (MVA) and adenoviral vectors encoding ME.TRAP can enhance both short- and long
      term sterile protection against malaria. Protection persisted for at least 6
      months when simian adenoviruses AdCh63 and AdC9 were used as priming vectors.
      Kinetic analysis showed that the MVA boost made the adenoviral-primed T cells
      markedly more polyfunctional, with the number of gamma interferon (INF-gamma),
      tumor necrosis factor alpha (TNF-alpha), and interleukin-2 (IL-2) triple-positive
      and INF-gamma and TNF-alpha double-positive cells increasing over time, while INF
      gamma single-positive cells declined with time. However, IFN-gamma production
      prevailed as the main immune correlate of protection, while neither an increase
      of polyfunctionality nor a high integrated mean fluorescence intensity (iMFI)
      correlated with protection. These data highlight the ability of optimized viral
      vector prime-boost regimens to generate more protective and sustained CD8+ T-cell
      responses, and our results encourage a more nuanced assessment of the importance
      of inducing polyfunctional CD8(+) T cells by vaccination.

PMID- 19858307
TI  - Genetic fusions of heat-labile (LT) and heat-stable (ST) toxoids of porcine
      enterotoxigenic Escherichia coli elicit neutralizing anti-LT and anti-STa
      antibodies.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal
      disease in humans and farm animals. E. coli fimbriae, or colonization factor
      antigens (CFAs), and enterotoxins, including heat-labile enterotoxins (LT) and
      heat-stable enterotoxins (ST), are the key virulence factors in ETEC diarrhea.
      Unlike fimbriae or LT, STa has not often been included as an antigen in
      development of vaccines against ETEC diarrhea because of its poor immunogenicity.
      STa becomes immunogenic only after being coupled with a strongly immunogenic
      carrier protein. However, native or shorter STa antigens either had to retain
      toxic activity in order to become antigenic or elicited anti-STa antibodies that
      were not sufficiently protective. In this study, we genetically mutated the
      porcine LT (pLT) gene for a pLT(192(R-->G)) toxoid and the porcine STa (pSTa)
      gene for three full-length pSTa toxoids [STa(11(N-->K)), STa(12(P-->F)), and
      STa(13(A-->Q))] and used the full-length pLT(192) as an adjuvant to carry the
      pSTa toxoid for pLT(192):pSTa-toxoid fusion antigens. Rabbits immunized with
      pLT(192):pSTa(12) or pLT(192):pSTa(13) fusion protein developed high titers of
      anti-LT and anti-STa antibodies. Furthermore, rabbit antiserum and antifecal
      antibodies were able to neutralize purified cholera toxin (CT) and STa toxin. In
      addition, preliminary data suggested that suckling piglets born by a sow
      immunized with the pLT(192):pSTa(13) fusion antigen were protected when
      challenged with an STa-positive ETEC strain. This study demonstrated that pSTa
      toxoids are antigenic when fused with a pLT toxoid and that the elicited anti-LT
      and anti-STa antibodies were protective. This fusion strategy could provide
      instructive information to develop effective toxoid vaccines against ETEC
      associated diarrhea in animals and humans.

PMID- 19858308
TI  - Helicobacter pylori lipopolysaccharides upregulate toll-like receptor 4
      expression and proliferation of gastric epithelial cells via the MEK1/2-ERK1/2
      mitogen-activated protein kinase pathway.
AB  - Helicobacter pylori is recognized as an etiological agent of gastroduodenal
      diseases. H. pylori produces various toxic substances, including
      lipopolysaccharide (LPS). However, H. pylori LPS exhibits extremely weakly
      endotoxic activity compared to the typical LPS, such as that produced by
      Escherichia coli, which acts through Toll-like receptor 4 (TLR4) to induce
      inflammatory molecules. The gastric epithelial cell lines MKN28 and MKN45 express
      TLR4 at very low levels, so they show very weak interleukin-8 (IL-8) production
      in response to E. coli LPS, but pretreatment with H. pylori LPS markedly enhanced
      IL-8 production induced by E. coli LPS by upregulating TLR4 via TLR2 and the
      MEK1/2-ERK1/2 pathway. The transcription factor NF-Y was activated by this signal
      and promoted transcription of the tlr4 gene. These MEK1/2-ERK1/2 signal-mediated
      activities were more potently activated by LPS carrying a weakly antigenic
      epitope, which is frequently found in gastric cancers, than by LPS carrying a
      highly antigenic epitope, which is associated with chronic gastritis. H. pylori
      LPS also augmented the proliferation rate of gastric epithelial cells via the
      MEK1/2-ERK1/2 pathway. H. pylori LPS may be a pathogenic factor causing gastric
      tumors by enhancing cell proliferation and inflammation via the MEK1/2-ERK1/2
      mitogen-activated protein kinase cascade in gastric epithelial cells.

PMID- 19858310
TI  - Candida albicans releases soluble factors that potentiate cytokine production by
      human cells through a protease-activated receptor 1- and 2-independent pathway.
AB  - The innate immune system recognizes pathogen-associated molecular patterns
      (PAMPs) through pattern recognition receptors (PRR) and transduces downstream
      signaling to activate the host defense. Here we report that in addition to direct
      PAMP-PRR interactions, live Candida albicans cells can release soluble factors to
      actively potentiate interleukin-6 (IL-6) and IL-8 production induced in human
      mononuclear cells by the fungi. Although protease-activated receptor 1 (PAR1) and
      PAR2 ligation can moderately upregulate Toll-like receptor 4 (TLR4)-mediated IL-8
      production, no effect on the C. albicans-induced cytokine was apparent.
      Similarly, the blockade of PAR signaling did not reverse the potentiation of
      cytokine production induced by soluble factors released by C. albicans. In
      conclusion, C. albicans releases soluble factors that potentiate cytokine release
      in a PAR1/2-independent manner. Thus, human PAR1 and PAR2 have a redundant role
      in the activation of human cells by C. albicans.

PMID- 19858311
TI  - Quorum sensing negatively regulates hemolysin transcriptionally and
      posttranslationally in Vibrio cholerae.
AB  - Recent work has shown that in addition to cholera toxin (CT) and the toxin
      coregulated pilus (TCP), other cytotoxic proteins in Vibrio cholerae also cause
      disease symptoms, and this is particularly evident in strains lacking CT. One
      such protein is the hemolysin encoded by hlyA. Here we show that, like CT and
      TCP, HlyA is repressed by the quorum-sensing-regulated transcription factor HapR.
      This repression occurs on two levels: one at the transcriptional level that is
      independent of the metalloprotease HapA and one at the posttranslational level
      that is mediated by HapA. The transcriptional regulation is significantly more
      apparent on solid media than in liquid cultures. This is the first time that
      hemolysis has been shown to be directly regulated by quorum sensing in V.
      cholerae, and it is interesting that, like other virulence factors, HlyA is also
      repressed by HapR, which is expressed late in infection.

PMID- 19858309
TI  - Characterization of a conditional bosR mutant in Borrelia burgdorferi.
AB  - Borrelia burgdorferi, the etiological agent of Lyme disease, adapts to unique
      host environments as a consequence of its complex life cycle that spans both
      arthropod and mammalian species. In this regard, B. burgdorferi must adapt to
      various environmental signals, pHs, temperatures, and O(2) and CO(2) levels to
      establish infectious foci. We hypothesize that the BosR protein functions as a
      global regulator that is required for both borrelial oxidative homeostasis and
      pathogenesis. To assess the role of BosR in B. burgdorferi, we constructed an
      IPTG (isopropyl-beta-d-thiogalactopyranoside)-regulated bosR strain. The
      selective decrease of bosR resulted in a change in growth when cells were
      cultured either anaerobically or microaerobically; however, a distinct growth
      defect was observed for anaerobically grown B. burgdorferi relative to the growth
      attenuation observed for microaerobically grown B. burgdorferi. B. burgdorferi
      cells in which BosR levels were reduced were more sensitive to hydrogen peroxide
      and produced lower levels of NapA (Dps) and SodA, proteins involved in the
      oxidative stress response. In addition, the levels of OspC and DbpA were also
      induced coincident with increased BosR levels, suggesting that BosR interfaces
      with the RpoS regulatory cascade, which is known to modulate virulence gene
      expression in B. burgdorferi. Taken together, these results indicate that BosR is
      involved in the resistance of B. burgdorferi to oxidative stressors and affects
      the expression of genes, either directly or indirectly, whose products are
      important in borrelial pathogenesis.

PMID- 19858312
TI  - Understanding adolescent caffeine use: connecting use patterns with expectancies,
      reasons, and sleep.
AB  - Little is known about adolescents' caffeine use, yet caffeinated soda, and more
      recently coffee and energy drinks, are part of youth culture. This study examines
      adolescents' caffeine use and, using cluster analysis, identifies three groups of
      caffeine users who differed in their reasons for use, expectancies, and sleep
      behaviors. In this high school student sample (N = 197), 95% of participants
      reported recent caffeine use-most often soda-where typical first use of the day
      was in the evening. Results reveal that adolescents in the mixed use and high
      soda use groups consumed similar amounts of soda, reporting significantly more
      use than the low caffeine use group. In contrast with high soda users, mixed
      users drank more coffee, expected more dependence symptoms and energy enhancement
      from caffeine, and were more likely to report getting up early, daytime
      sleepiness, and using caffeine to get through the day.

PMID- 19858313
TI  - Project ACTS: an intervention to increase organ and tissue donation intentions
      among African Americans.
AB  - This study sought to evaluate the effectiveness of Project ACTS: About Choices in
      Transplantation and Sharing, which was developed to increase readiness for organ
      and tissue donation among African American adults. Nine churches (N = 425
      participants) were randomly assigned to receive donation education materials
      currently available to consumers (control group) or Project ACTS educational
      materials (intervention group). The primary outcomes assessed at 1-year follow-up
      were readiness to express donation intentions via one's driver's license, donor
      card, and discussion with family. Results indicate a significant interaction
      between condition and time on readiness to talk to family such that participants
      in the intervention group were 1.64 times more likely to be in action or
      maintenance at follow-up than were participants in the control group (p = .04).
      There were no significant effects of condition or condition by time on readiness
      to be identified as a donor on one's driver's license and by carrying a donor
      card. Project ACTS may be an effective tool for stimulating family discussion of
      donation intentions among African Americans although additional research is
      needed to explore how to more effectively affect written intentions.

PMID- 19858314
TI  - Examining elementary school--aged children's self-efficacy and proxy efficacy for
      fruit and vegetable consumption.
AB  - Children's self-efficacy for fruit and vegetable consumption (FVC) and proxy
      efficacy to influence others to make fruit and vegetables (FV) available may
      influence their FVC. A previous investigation has demonstrated that self-efficacy
      for fruit consumption, self-efficacy for vegetable consumption, proxy efficacy to
      influence parents to make FV available, and proxy efficacy to influence after
      school staff to make FV available can be measured with four independent but
      related scales. The purpose of the present investigation is to confirm this
      factor structure and determine if the scales were invariant across gender,
      ethnicity, and socioeconomic status (SES) subgroups of children attending after
      school programs. Results provide further validity evidence for the four
      correlated scales. In addition, results confirm measurement invariance across
      gender, SES, and ethnicity, confirming the unbiased generalizability of the
      current measure to these demographic groups. Lastly, tests of population
      heterogeneity reveal no meaningful differences in self- and proxy efficacy among
      gender, SES, and ethnicity subgroups.

PMID- 19858316
TI  - Lack of association between urinary iodine excretion and successful thyroid
      ablation in thyroid cancer patients.
AB  - BACKGROUND: Low-iodine diet is prescribed before (131)I administration in
      patients with differentiated thyroid cancer, although no study has properly
      quantified its clinical benefit. OBJECTIVE: Our study aimed to evaluate the
      association between urinary iodine excretion (UIE) and (131)I ablation by
      correlating UIE with the rate of successful ablation. PATIENTS: We
      retrospectively studied 201 differentiated thyroid cancer patients who had
      received (131)I therapy and posttherapy whole-body scan (WBS) for remnant
      ablation after either thyroid hormone withdrawal (THW group, n = 125) or
      recombinant human TSH (rhTSH group, n = 76). The outcome of thyroid ablation was
      assessed using two different criteria: no visible uptake at control WBS 8-12
      months after ablation or no visible uptake plus undetectable stimulated serum
      thyroglobulin (Tg). RESULTS: According to the criterion of no visible uptake,
      84.6% of the patients were successfully ablated, with no significant difference
      between THW and rhTSH groups. Mean UIE at the time of ablation was 132 +/- 160
      microg/liter, not significantly different between patients of the THW and rhTSH
      groups. There was no significant difference in UIE between ablated or nonablated
      patients both in the whole group and the rhTSH or THW groups. According to the
      criterion of no visible uptake plus undetectable stimulated serum Tg (in anti-Tg
      negative patients) at control WBS 8-12 months after ablation, UIE was not
      significantly different in ablated and nonablated patients. CONCLUSIONS: Our
      study indicates that the body iodine content is not an important determinant of
      thyroid ablation, when preparing the patients with either THW or rhTSH.

PMID- 19858315
TI  - Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type
      determine pulsatile growth hormone secretion in healthy women: studies using
      submaximal agonist drive and an estrogen clamp.
AB  - CONTEXT: GH-releasing peptide (GHRP), GHRH, and somatostatin are physiological
      regulators of pulsatile GH secretion. HYPOTHESIS: Age, independently of abdominal
      visceral fat (AVF) and basal (nonpulsatile) GH secretion, damps pulsatile GH
      secretion driven by physiological (rather than pharmacological) amounts of GHRP
      and GHRH in an experimentally controlled estradiol (E(2)) milieu. DESIGN AND
      SETTING: A prospectively randomized, double-blind parallel-cohort study was
      conducted at an academic medical center. PARTICIPANTS: Community-dwelling healthy
      premenopausal (PRE, age 24 +/- 0.8 yr, n = 20) and postmenopausal (POST, age 63
      +/- 1.8 yr, n = 22) women participated in the study. INTERVENTIONS: Gonadal-axis
      down-regulation with leuprolide was followed by randomized addback of placebo or
      transdermal E(2) and separate-day iv bolus injections of a half-maximally
      stimulatory dose of GHRP-2 or GHRH (each 0.33 mug/kg). ANALYSIS: Three-way
      analysis of covariance included main factors age, E(2) status, and secretagogue
      type and covariates AVF and basal GH secretion. RESULTS: Submaximally stimulated
      pulsatile GH secretion was positively determined by PRE vs. POST age (P < 0.001),
      E(2) repletion vs. depletion (P = 0.001) and GHRP-2 vs. GHRH stimulation (P <
      0.001), after adjustment for AVF and basal secretion. E(2) vs. placebo elevated
      fasting mean GH concentrations in both PRE and POST women (P = 0.006) but
      increased basal (nonpulsatile) GH secretion in PRE only (P = 0.002). PRE vs. POST
      age prolonged GHRH-driven GH secretory bursts by 36% (P = 0.006). CONCLUSION: PRE
      vs. POST age, E(2) availability, and physiological peptide drive are triple
      determinants of pulsatile GH secretion independently of abdominal visceral fat
      and nonpulsatile GH secretion in healthy women.

PMID- 19858317
TI  - Increased apolipoprotein AI production rate and redistribution of high-density
      lipoprotein size induced by estrogen plus progestin as oral contraceptive.
AB  - CONTEXT: The impact of estrogen plus progestin as an oral contraceptive on high
      density lipoprotein (HDL) apolipoprotein (apo) AI metabolism in humans is poorly
      understood. OBJECTIVES: This study was designed to measure the in vivo effect of
      Moneva (30 microg ethinylestradiol, 75 microg gestodene) on HDL apoAI production
      rate and fractional catabolic rate. DESIGN: Using (13)C-leucine, we performed two
      kinetic studies in the fed state in 10 normolipidemic young women, before and 3
      months after beginning Moneva. RESULTS: On Moneva, serum triglycerides increased
      by 12% (P = 0.03) in the fed state, whereas low-density lipoprotein and HDL
      cholesterol remained unchanged. HDL apoAI pool size and production rate were
      increased by 9.2% (67.3 +/- 7.1 vs. 61.6 +/- 6.7 mg x kg(-1); P = 0.05) and 26.5%
      (14.3 +/- 2.7 vs. 11.3 +/- 2.2 mg x kg(-1) x d(-1); P = 0.02), respectively. HDL
      apoAI fractional catabolic rate was not significantly modified. Three-month
      treatment by Moneva induced a shift of HDL size distribution from HDL2 toward
      HDL3 (HDL3 = 51.5 +/- 8.1 vs. 46.5 +/- 9.2% of total HDL; P = 0.02) and an
      increase in the proportion of apoAI among HDL components (38.8 +/- 4.3 vs. 34.4
      +/- 2.8%; P = 0.01). CONCLUSION: Oral contraception by estrogen plus progestin
      induces changes in HDL apoAI metabolism characterized by an increase in
      production rate and pool size, with a higher proportion of HDL3 particles.
      Whether or not these changes are beneficial to prevent atherosclerosis has to be
      explored further.

PMID- 19858318
TI  - Clinical, immunological, and genetic features of autoimmune primary adrenal
      insufficiency: observations from a Norwegian registry.
AB  - OBJECTIVE: Primary adrenal insufficiency [Addison's disease (AD)] is rare, and
      systematic studies are few, mostly conducted on small patient samples. We aimed
      to determine the clinical, immunological, and genetic features of a national
      registry-based cohort. DESIGN: Patients with AD identified through a nationwide
      search of diagnosis registries were invited to participate in a survey of
      clinical features, health-related quality of life (HRQoL), autoantibody assays,
      and human leukocyte antigen (HLA) class II typing. RESULTS: Of 664 registered
      patients, 64% participated in the study. The prevalence of autoimmune or
      idiopathic AD in Norway was 144 per million, and the incidence was 0.44 per
      100,000 per year (1993-2007). Familial disease was reported by 10% and autoimmune
      comorbidity by 66%. Thyroid disease was most common (47%), followed by type 1
      diabetes (12%), vitiligo (11%), vitamin B12 deficiency (10%), and premature
      ovarian insufficiency (6.6% of women). The mean daily treatment for AD was 40.5
      mg cortisone acetate and 0.1 mg fludrocortisone. The mean Short Form 36 vitality
      scores were significantly diminished from the norm (51 vs. 60), especially among
      those with diabetes. Concomitant thyroid autoimmunity did not lower scores. Anti
      21-hydroxylase antibodies were found in 86%. Particularly strong susceptibility
      for AD was found for the DR3-DQ2/ DRB1*0404-DQ8 genotype (odds ratio, 32; P = 4 x
      10(-17)), which predicted early onset. CONCLUSIONS: AD is almost exclusively
      autoimmune, with high autoimmune comorbidity. Both anti-21-hydroxylase antibodies
      and HLA class II can be clinically relevant predictors of AD. HRQoL is reduced,
      especially among diabetes patients, whereas thyroid disease did not have an
      impact on HRQoL. Treatment modalities that improve HRQoL are needed.

PMID- 19858319
TI  - Effect of transdermal teriparatide administration on bone mineral density in
      postmenopausal women.
AB  - CONTEXT: Treatment of osteoporosis with an anabolic agent, teriparatide [human
      PTH 1-34 (TPTD)], is effective in reducing incident fractures, but patient
      resistance to daily sc injections has limited its use. A novel transdermal patch,
      providing a rapid, pulse delivery of TPTD, may provide a desirable alternative.
      OBJECTIVE: The aim of the study was to determine the safety and efficacy of a
      novel transdermal TPTD patch compared to placebo patch and sc TPTD 20-microg
      injection in postmenopausal women with osteoporosis. DESIGN: Our study consisted
      of 6-month, randomized, placebo-controlled, positive control, multidose daily
      administration. PATIENTS: We enrolled 165 postmenopausal women (mean age, 64 yr)
      with osteoporosis. INTERVENTIONS: A TPTD patch with a 20-, 30-, or 40-microg dose
      or a placebo patch was self-administered daily for 30-min wear time, or 20 microg
      of TPTD was injected daily. OUTCOMES: The primary efficacy measure was mean
      percentage change in lumbar spine bone mineral density (BMD) from baseline at 6
      months. RESULTS: TPTD delivered by transdermal patch significantly increased
      lumbar spine BMD vs. placebo patch in a dose-dependent manner at 6 months (P <
      0.001). TPTD 40-microg patch increased total hip BMD compared to both placebo
      patch and TPTD injection (P < 0.05). Bone turnover markers (procollagen type I N
      terminal propeptide and C-terminal cross-linked telopeptide of type I collagen)
      increased from baseline in a dose-dependent manner in all treatment groups and
      were all significantly different from placebo patch (P < 0.001). All treatments
      were well tolerated, and no prolonged hypercalcemia was observed. CONCLUSION:
      Transdermal patch delivery of TPTD in postmenopausal women with osteoporosis for
      6 months is safe and effective in increasing lumbar spine and total hip BMD.

PMID- 19858321
TI  - How to adapt effective programs for use in new contexts.
AB  - A wide variety of underused effective HIV prevention programs exist. This article
      describes sources for obtaining such effective programs and issues to consider in
      selecting an existing effective program for use with one's priority population.
      It also discusses seven steps involved in adapting an effective program to meet
      the needs of a new context while preserving core components (what made, or is
      believed to have made, the intervention effective in the first place) and best
      practices (characteristics common to effective programs). Although the examples
      presented are from the HIV prevention field, the seven-step framework is
      applicable to the adaptation of effective programs in other health promotion and
      disease prevention arenas.

PMID- 19858320
TI  - Serum markers of bone turnover are increased at six and 18 months after Roux-en-Y
      bariatric surgery: correlation with the reduction in leptin.
AB  - OBJECTIVE: The aim of the study was to examine serum markers of bone turnover at
      6 and 18 months after Roux-en-Y gastric bypass surgery. PARTICIPANTS: Ten women
      and 10 men [body mass index (BMI), 50.2 +/- 8.4 kg/m(2)] were studied at 6
      months; 10 women and nine men (BMI, 47.2 +/- 6.6 kg/m(2)) were studied at 18
      months after surgery. MAIN OUTCOME MEASURES: Serum osteocalcin, bone specific
      alkaline phosphatase (BAP), N-telopeptide of type 1 collagen (NTX), PTH, 25
      hydroxy vitamin D, and leptin were measured. RESULTS: BMI was reduced 32.7 +/-
      6.2% at 6 months after surgery. Serum osteocalcin (6.9 +/- 2.4 to 10.9 +/- 2.6
      ng/ml; P < 0.0001), BAP (14.2 +/- 3.7 to 16.4 +/- 4.5 ng/ml; P = 0.04), and NTX
      (10.9 +/- 1.7 to 19.6 +/- 5.3 nm bone collagen equivalents; P < 0.0001) were
      increased. Calcium, phosphate, and PTH were unchanged, but 25-hydroxy vitamin D
      increased (16.0 +/- 8.9 vs. 26.9 +/- 10.6 ng/ml; P <0.0001). The increase in NTX
      correlated with reduction in serum leptin (r = 0.58; P = 0.007). BMI was reduced
      40.9 +/- 7.5% at 18 months after surgery. Serum BAP (17.6 +/- 5.3 to 22.2 +/- 7.8
      ng/ml; P = 0.0017) and NTX (10.8 +/- 2.7 to 16.9 +/- 5.5 nm bone collagen
      equivalents; P < 0.0001) were increased. Calcium, phosphate, and PTH were
      unchanged, but 25-hydroxy vitamin D increased (17.7 +/- 7.6 to 25.6 +/- 6.8
      ng/ml; P < 0.0001). The increase in NTX correlated with reduction in BMI (r =
      0.58; P = 0.009) and leptin (r = 0.45; P = 0.04) and the increase in serum 25
      hydroxy vitamin D (r = 0.43; P = 0.05). In multiple regression (adjusted model
      R(2) 0.263; P = 0.013), reduction in leptin was a significant predictor of
      increase in NTX (P = 0.016), but changes in BMI and 25-hydroxy vitamin D were
      not. CONCLUSIONS: Weight loss after bariatric surgery is associated with long
      term increase in serum markers of bone turnover. The increase in NTX is related
      to the decrease in leptin, which may signal caloric restriction to the skeleton.

PMID- 19858322
TI  - Building on partnerships: reconnecting kids with nature for health benefits.
AB  - In April 2008, several federal and nonprofit agencies organized an informational
      Web-based meeting titled "Reconnecting Kids With Nature for Health Benefits."
      This online meeting was convened by the Society for Public Health Education and
      delivered to public health educators, health professionals, environmental
      educators, and land conservationists to raise awareness of national efforts to
      promote children's involvement in outdoor recreation. This article describes
      eight programs discussed at this meeting. For public health professionals,
      partnership with land-management agencies conducting such programs may be an
      effective way to increase physical activity levels among children.

PMID- 19858324
TI  - Identity of the elusive IgM Fc receptor (FcmuR) in humans.
AB  - Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been
      extensively characterized, FcR for IgM (FcmuR) has defied identification. By
      retroviral expression and functional cloning, we have identified a complementary
      DNA (cDNA) encoding a bona fide FcmuR in human B-lineage cDNA libraries. FcmuR is
      defined as a transmembrane sialoglycoprotein of approximately 60 kD, which
      contains an extracellular Ig-like domain homologous to two other IgM-binding
      receptors (polymeric Ig receptor and Fcalpha/muR) but exhibits an exclusive Fcmu
      binding specificity. The cytoplasmic tail of FcmuR contains conserved Ser and Tyr
      residues, but none of the Tyr residues match the immunoreceptor tyrosine-based
      activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types
      expressing FcmuR are adaptive immune cells, including B and T lymphocytes. After
      antigen-receptor ligation or phorbol myristate acetate stimulation, FcmuR
      expression was up-regulated on B cells but was down-modulated on T cells,
      suggesting differential regulation of FcmuR expression during B and T cell
      activation. Although this receptor was initially designated as Fas apoptotic
      inhibitory molecule 3, or TOSO, our results indicate that FcmuR per se has no
      inhibitory activity in Fas-mediated apoptosis and that such inhibition is only
      achieved when anti-Fas antibody of an IgM but not IgG isotype is used for
      inducing apoptosis.

PMID- 19858325
TI  - The lung vascular filter as a site of immune induction for T cell responses to
      large embolic antigen.
AB  - The bloodstream is an important route of dissemination of invading pathogens.
      Most of the small bloodborne pathogens, like bacteria or viruses, are filtered by
      the spleen or liver sinusoids and presented to the immune system by dendritic
      cells (DCs) that probe these filters for the presence of foreign antigen (Ag).
      However, larger pathogens, like helminths or infectious emboli, that exceed 20
      microm are mostly trapped in the vasculature of the lung. To determine if Ag
      trapped here can be presented to cells of the immune system, we used a model of
      venous embolism of large particulate Ag (in the form of ovalbumin [OVA]-coated
      Sepharose beads) in the lung vascular bed. We found that large Ags were presented
      and cross-presented to CD4 and CD8 T cells in the mediastinal lymph nodes (LNs)
      but not in the spleen or liver-draining LNs. Dividing T cells returned to the
      lungs, and a short-lived infiltrate consisting of T cells and DCs formed around
      trapped Ag. This infiltrate was increased when the Toll-like receptor 4 was
      stimulated and full DC maturation was induced by CD40 triggering. Under these
      conditions, OVA-specific cytotoxic T lymphocyte responses, as well as humoral
      immunity, were induced. The T cell response to embolic Ag was severely reduced in
      mice depleted of CD11c(hi) cells or Ly6C/G(+) cells but restored upon adoptive
      transfer of Ly6C(hi) monocytes. We conclude that the lung vascular filter
      represents a largely unexplored site of immune induction that traps large
      bloodborne Ags for presentation by monocyte-derived DCs.

PMID- 19858327
TI  - Mirrors and resistance exercise, do they influence affective responses?
AB  - The purpose of this study was to examine affective responses during and following
      resistance exercise in a mirrored environment. Thirty-two females completed three
      sessions. During session one, exercise intensity was determined for the
      subsequent two sessions. During the next two sessions participants performed
      eight exercises either with or without mirrors. Affect was measured prior to,
      during, immediately following and 15 minutes post-exercise. Affect was more
      pleasant and activated during and following exercise, but did not differ by
      condition. The inability to find a difference in mirrored condition may be a
      result of participants using the mirrors for technique as opposed to self
      evaluation purposes.

PMID- 19858326
TI  - Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the
      virus to dendritic cells.
AB  - Semen is the main vector for HIV-1 dissemination worldwide. It contains three
      major sources of infectious virus: free virions, infected leukocytes, and
      spermatozoa-associated virions. We focused on the interaction of HIV-1 with human
      spermatozoa and dendritic cells (DCs). We report that heparan sulfate is
      expressed in spermatozoa and plays an important role in the capture of HIV-1.
      Spermatozoa-attached virus is efficiently transmitted to DCs, macrophages, and T
      cells. Interaction of spermatozoa with DCs not only leads to the transmission of
      HIV-1 and the internalization of the spermatozoa but also results in the
      phenotypic maturation of DCs and the production of IL-10 but not IL-12p70. At low
      values of extracellular pH (approximately 6.5 pH units), similar to those found
      in the vaginal mucosa after sexual intercourse, the binding of HIV-1 to the
      spermatozoa and the consequent transmission of HIV-1 to DCs were strongly
      enhanced. Our observations support the notion that far from being a passive
      carrier, spermatozoa acting in concert with DCs might affect the early course of
      sexual transmission of HIV-1 infection.

PMID- 19858328
TI  - Changing nutrition, physical activity and body weight among student nurses and
      midwives: effects of a planning intervention and self-efficacy beliefs.
AB  - The study tested if effects of a planning intervention on fruit and vegetable
      consumption, physical activity and body weight may be moderated by self-efficacy.
      Student nurses and midwives (N = 182) were randomly assigned to the planning or
      the control condition. The intervention included action and coping plans and was
      followed by two booster sessions. Follow-up took place at two months after last
      booster session. The intervention affected fruit and vegetable intake.
      Additionally, body mass index of overweight participants was reduced. Baseline
      self-efficacy moderated the effects of the intervention: only respondents
      reporting strong efficacy beliefs improved their diet and exercise.

PMID- 19858329
TI  - Anxiety sensitivity and catastrophizing: associations with pain and somatization
      in non-clinical children.
AB  - This study examined the relationships among anxiety sensitivity (AS),
      catastrophizing, somatization and pain in 240 non-clinical children (121 girls;
      mean age = 12.7 years). Children with pain problems (n = 81; 33.8%) reported
      greater AS and catastrophizing (ps < .01) relative to children without pain
      problems. AS but not catastrophizing was significantly associated with current
      pain. However, both AS and catastrophizing were significantly associated with
      somatization. AS and catastrophizing represent related but partially distinct
      cognitive constructs that may be targeted by interventions aimed at alleviating
      pain and somatization in children.

PMID- 19858330
TI  - The impact of gender and hypothalamic pituitary adrenal activity on depressive
      symptoms following surgical stress.
AB  - The impact of gender and cortisol levels on depression following planned surgery
      was examined in 95 men and women. Patients were assessed prior to surgery and at
      one and three months following surgery. Higher cortisol levels conferred greater
      risk for depression at one and three months following surgery. This effect was
      stronger for men than women at one month following surgery, but did not differ
      between genders at three months post-surgery. Results support a mechanistic role
      of HPA alterations in depression following a surgical stressor that differs in
      strength between men and women.

PMID- 19858331
TI  - The individual health burden of acne: appearance-related distress in male and
      female adolescents and adults with back, chest and facial acne.
AB  - This study examined appearance-related distress in patients with acne. One
      hundred and thirty-two people attending a specialist acne clinic completed
      questionnaires including the Derriford Appearance Scale and three self-rated acne
      scales covering more (facial) and less visible (chest, back) acne sites. Women
      with acne demonstrated greater self-consciousness of appearance and negative self
      concept than men. Subjective rating of severity of facial acne was significantly
      associated with increased social self-consciousness in women, but not in men.
      Back acne was significantly associated with sexual and bodily self-consciousness
      of appearance in both men and women. Patients 20 years and above were
      significantly more likely to suffer appearance-related distress than 16-19-year
      olds. Although not a key focus of this study, ethnicity was also implicated in
      appearance concern arising from acne.

PMID- 19858332
TI  - Protection motivation theory and physical activity: a longitudinal test among a
      representative population sample of Canadian adults.
AB  - The purpose of this study was to examine the Protection Motivation Theory (PMT)
      to predict physical activity (PA) behaviour in a large, population-based sample
      of adults. One thousand six hundred and two randomly selected individuals
      completed two telephone interviews over two consecutive six-month periods
      assessing PMT constructs. PMT explained 35 per cent and 20 per cent of the
      variance in intention and behaviour respectively. Coping cognitions as moderators
      of threat explained 1 per cent of the variance in intention and behaviour. Age
      and gender as moderators of threat did not provide additional variance in the
      models. We conclude that salient PMT predictors (e.g. self-efficacy) may guide
      the development of effective PA interventions in the general population.

PMID- 19858333
TI  - Predictors of familism in the caregiver role: a pilot study.
AB  - This study aimed to investigate whether age, gender and ethnicity were predictive
      of familism in caregivers; and whether familism was associated with coping. Forty
      five British South-Asian and 43 British Caucasian caregivers completed a cross
      sectional questionnaire of demographics, the brief Cope and the Heller Familism
      scale. Asian and younger caregivers endorsed higher levels of familisim than
      Caucasian and older caregivers. In the final model, demographic variables,
      humour, religious, active and instrumental coping explained 41 per cent of the
      variance in caregiver familism. The findings suggest the need to consider
      familism values when providing caregiver services to minimize the potential
      negative impact of caregiving.

PMID- 19858334
TI  - 'Football is good for your sleep': favorable sleep patterns and psychological
      functioning of adolescent male intense football players compared to controls.
AB  - It is commonly assumed that physical activity exerts a favorable impact on sleep,
      although scientific evidence is lacking. This study investigated the impact of
      football sports on the sleep patterns of 36 male chronic and intense football
      players and 34 controls. Participants completed a sleep log for seven consecutive
      days. Compared to controls, football players reported shorter sleep onset
      latency, fewer awakenings, higher scores of sleep quality and a lower variability
      of sleep from weekdays to weekends. The findings suggest that football sports
      activity is positively associated with both quantitative and qualitative
      dimensions of sleep.

PMID- 19858335
TI  - Crossed evaluations of temptation to drink, strain and adjustment in couples with
      alcohol problems.
AB  - The aim was to describe discrepancies between patients' and spouses' dyadic
      adjustment scores, spouse strain and patients' temptation to drink during
      abstinence. Patients overestimated the dyadic adjustment scores of their partner
      and spouses underestimated patients' scores. Spouses overestimated patients'
      temptation to drink. Correlations between patients' and spouses' scores were
      generally high (.61 to .78) except for five measures of spouse strain which were
      lower (.31 to .50). Results show discrepancies concerning marital function and
      the temptation to drink which could be important when planning treatment and
      prevention of relapse.

PMID- 19858336
TI  - Development and validation of the Physician-Patient Humor Rating Scale.
AB  - The purpose of this study was the development of a rating instrument to assess
      the use of humor in physician- patient interactions, and to compare humor use as
      a function of patients' socioeconomic status. The 46-item Physician-Patient Humor
      Rating Scale (PPHRS) was used to rate 246 audiotaped primary care interactions.
      Four subscales were reliable and valid, demonstrating correlations with patient
      satisfaction and reports of physician humor, with physician satisfaction and with
      separate affective communication ratings. There was a significant difference in
      use of humor as a function of patient socioeconomic status, such that there was
      greater mutual trust between physicians and high versus low income patients.

PMID- 19858337
TI  - Using the constructive narrative perspective to understand physical activity
      reasoning schema in sedentary adults.
AB  - We used the Constructive Narrative Perspective (CNP), a three-level,
      progressively complex reasoning schema, to examine how individuals perceive
      barriers to physical activity. Sedentary adults (N = 23) aged 50 years and older
      (M = 65.23; SD = 6.03) participated in semi-structured interviews regarding their
      reasons for physical inactivity. The results provided initial support for using
      the CNP framework. Level II (self-relevant) and Level III (cognitive-affective
      schema-related) reasons were most commonly reported. Level I (evidence-based)
      reasons were less commonly reported. The CNP framework could become a useful tool
      in tailoring intervention strategies based upon progressively more complex
      reasoning schema.

PMID- 19858338
TI  - Interrelationships of adult attachment orientations, health status and worrying
      among fibromyalgia patients.
AB  - This study examined associations between adult attachment dimensions, perceived
      health status and worrying (coping strategy with chronic pain), and explored
      whether worrying mediated observed relationships between attachment dimensions
      and health outcomes within a sample of 128 Portuguese female fibromyalgia
      patients. Physical health status was inversely correlated with dependence and
      worrying; mental health status was positively correlated with trust, and
      inversely related to attachment-related ambivalence, dependence and worrying.
      Finally, worrying mediated relationships between dependence and both physical and
      mental health status; moreover, worrying partially mediated the relationship
      between ambivalence and mental health status. Implications of the findings are
      discussed.

PMID- 19858339
TI  - Strength of exercise identity and identity-exercise consistency: affective and
      social cognitive relationships.
AB  - This study examined Identity Theory hypotheses about identity-behaviour
      consistency. Exercise-identity strength and judgments about consistency were
      hypothesized to relate to perceptions of percent consistency and frequency of
      vigorous exercise. Identity strength and percent consistency were hypothesized to
      interact in their relationship with affective reactions to extent of consistency.
      Measures of exercise-identity strength, perceived consistency, exercise
      frequency, self-regulatory efficacy and consistency-related affect were completed
      by 528 exercisers. Exercise-identity strength and consistency judgments related
      to percent consistency and exercise frequency. Exercise-identity strength and
      percent consistency interacted in their relationship with consistency-related
      affect and also were related to self-regulatory efficacy.

PMID- 19858340
TI  - The influence of family-work role experience and mastery on psychological health
      of Chinese employed mothers.
AB  - Four-hundred-and-thirty-five Chinese married nurses with children were surveyed
      on their family-work role experience, sense of mastery, and psychological
      distress. Hierarchical regression analyses showed spillover effects of role
      experience on psychological health as well as asymmetrical permeability of family
      and work boundaries. The hypothesis that mastery acted as a moderator between
      role experience and psychological health was supported. In general, a higher
      level of mastery augmented positive but mitigated negative influence of role
      experience on psychological functioning. Findings provide useful information to
      practitioners and policy makers on issues related to family-work stress and
      women's health in contemporary Chinese society.

PMID- 19858341
TI  - Representations of voluntary childlessness in the UK press, 1990-2008.
AB  - Representations of voluntary childlessness--the declaration by an individual that
      he or she does not wish to bear or raise children--were studied in 116 articles
      published in British national newspapers in the period 1990-2008. Media framing
      analysis was used to examine broad patterns of framing of the topic, identifying
      four frames: voluntary childlessness as an individual rights issue, as a form of
      resistance, as a social trend, and as a personal decision. These frames, it is
      argued, may act as potential 'scripts' for newspaper readers who are debating the
      decision to start a family.

PMID- 19858342
TI  - How do people change their diet?: an exploration into mechanisms of dietary
      change.
AB  - The present study explored how people change their diet over the course of their
      lifespan and what factors facilitate this process. Twenty participants'
      narratives were analysed using Interpretative Phenomenological Analysis. The
      participants' narratives indicated that diet changes can occur either with or
      without the individual's active involvement. We labelled these the active path
      and the passive path. Four themes emerged denoting the mechanisms of change:
      accumulation of evidence; trigger to action; imposed change; and seamless change.
      These results indicate that dietary changes may not be as infrequent and
      difficult as often assumed and highlight an array of new mechanisms which could
      be explored further to promote behaviour change.

PMID- 19858343
TI  - Illness acceptance, hospitalization stress and subjective health in a sample of
      chronic patients admitted to hospital.
AB  - The aim of this study was to examine the effects of illness acceptance on the
      subjective health of hospitalized chronic medical patients. Participants were 128
      patients with a previous diagnosis of chronic coronary artery disease, cancer, or
      chronic renal disease, who were admitted to a public hospital. Illness acceptance
      was associated with higher levels of subjective health. It was negatively related
      to psychological symptoms and positively to self-rated health, even after
      controlling for demographic variables, type of disease, years since diagnosis,
      health-related quality of life and hospitalization stress. Furthermore,
      acceptance mediated the effects of hospitalization stress on subjective health
      measures.

PMID- 19858344
TI  - Sleep apnea and psychological functioning in chronic fatigue syndrome.
AB  - Objectives were to explore: (1) whether sleep apnea/hypopnea syndrome (SAHS)
      should be considered a chronic fatigue syndrome (CFS) comorbidity, rather than a
      diagnostic exclusion criterion; and (2) to compare sleep/wake/ psychopathology in
      individuals with CFS, controls and another illness. Participants (CFS, SAHS,
      controls) completed questionnaires and were evaluated for SAHS; 68 percent were
      subsequently diagnosed with SAHS. CFS participants with and without SAHS did not
      differ. Both clinical groups were less well adjusted than controls. We conclude
      that SAHS should not be an exclusion criterion for CFS and that psychological
      problems in CFS seem a consequence of coping with illness.

PMID- 19858345
TI  - Fathers' views and understanding of their roles in families with a child with
      acute lymphoblastic leukaemia: an interpretative phenomenological analysis.
AB  - This study explored how fathers of children diagnosed with acute lymphoblastic
      leukaemia (ALL) perceived and understood the roles they had within their family
      over the course of their child's illness and treatment. In-depth semi-structured
      interviews were conducted with five fathers. Transcripts were analysed using
      interpretative phenomenological analysis (IPA). The major themes that emerged
      were: adjusting to the diagnosis; the experience of maternal gate-keeping;
      striving for normalization; experiences of giving and receiving support. Overall,
      the fathers perceived themselves as having significant responsibility in helping
      their child and family cope with the illness experience. Clinical implications,
      including the need for professionals to recognize and more openly acknowledge the
      father's position, are considered.

PMID- 19858346
TI  - Salim "Slim" Abdool Karim: attacking AIDS in South Africa. Interview by Amy
      Maxmen.

PMID- 19858348
TI  - Music: More than just a melody.

PMID- 19858347
TI  - KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity
      for HLA-A*11 while diminishing avidity for HLA-C.
AB  - Human killer cell immunoglobulin-like receptors (KIRs) are distinguished by
      expansion of activating KIR2DS, whose ligands and functions remain poorly
      understood. The oldest, most prevalent KIR2DS is KIR2DS4, which is represented by
      a variable balance between "full-length" and "deleted" forms. We find that full
      length 2DS4 is a human histocompatibility leukocyte antigen (HLA) class I
      receptor that binds specifically to subsets of C1+ and C2+ HLA-C and to HLA-A*11,
      whereas deleted 2DS4 is nonfunctional. Activation of 2DS4+ NKL cells was achieved
      with A*1102 as ligand, which differs from A*1101 by unique substitution of lysine
      19 for glutamate, but not with A*1101 or HLA-C. Distinguishing KIR2DS4 from other
      KIR2DS is the proline-valine motif at positions 71-72, which is shared with
      KIR3DL2 and was introduced by gene conversion before separation of the human and
      chimpanzee lineages. Site-directed swap mutagenesis shows that these two residues
      are largely responsible for the unique HLA class I specificity of KIR2DS4.
      Determination of the crystallographic structure of KIR2DS4 shows two major
      differences from KIR2DL: displacement of contact loop L2 and altered bonding
      potential because of the substitutions at positions 71 and 72. Correlation
      between the worldwide distributions of functional KIR2DS4 and HLA-A*11 points to
      the physiological importance of their mutual interaction.

PMID- 19858349
TI  - Use of pedometers to measure activity in COPD patients -- a step too far?

PMID- 19858350
TI  - Comparison of the effectiveness of music and progressive muscle relaxation for
      anxiety in COPD--A randomized controlled pilot study.
AB  - Acute effects of music and relaxation have not been evaluated in hospitalized
      subjects with chronic obstructive pulmonary disease (COPD). This study aims to
      evaluate the acute effects of music and progressive muscle relaxation (PMR) in
      hospitalized COPD subjects after a recent episode of exacerbation. A Randomized
      controlled study was performed of pre-test post-test design after recruiting 82
      COPD subjects from K.M.C hospitals. All patients were admitted for acute
      exacerbation and were medically stabilized. After being screened for the
      inclusion and exclusion criteria, 72 subjects were selected for the study.
      Demographic and baseline data was taken on the day subjects were screened. Music
      group listened to a self selected music of 60-80 beats per minute for 30 minutes.
      PMR group practiced relaxation through a pre-recorded audio of instructions of 16
      muscle groups. Outcome variables were Spielberger's state anxiety inventory
      (SSAI), Spielberger's trait anxiety inventory (STAI), dyspnea, systolic blood
      pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR) and respiratory
      rate (RR). There was statistically significant main effect across the sessions
      for state anxiety (F = 62.621, p = 0.000), trait anxiety (F = 19.528, p = 0.000),
      dyspnea (F = 122.227, p = 0.000), SBP (F = 63.885, p = 0.000), PR (F = 115.780, p
      = 0.000) and RR (F = 202.977, p = 0.000). There was statistically significant
      interaction effect between the two groups for state anxiety (F = 6.024, p =
      0.003), trait anxiety (F = 8.222, p = 0.000), dyspnea (F = 10.659, p = 0.000),
      SBP (F = 12.889, p = 0.000), PR (F = 4.746, p = 0.008) and RR (F = 12.078, p =
      0.000). There were greater changes observed after the second session in both
      groups however, change in DBP was not significant in either group. Music and PMR
      are effective in reducing anxiety and dyspnoea along with physiologic measures
      such as SBP, PR and RR in two sessions in COPD patients hospitalized with
      exacerbation. However, reductions in the music group were greater compared to the
      PMR group.

PMID- 19858351
TI  - Using pedometers to monitor walking activity in outcome assessment for pulmonary
      rehabilitation.
AB  - BACKGROUND: The purpose of this study was to determine whether a commercially
      available pedometer could detect changes in home-based walking activity among
      chronic obstructive pulmonary disease (COPD) patients completing pulmonary
      rehabilitation (PR). METHODS: Patients with COPD referred to outpatient PR wore a
      pedometer to count steps for 1 week at the beginning and 1 week at the end of PR.
      Patients also completed the 6-min walk test (6MWT), the Medical Research Council
      (MRC) dyspnea scale and the self-administered chronic respiratory disease
      questionnaire (CRQ) at the beginning and the end of PR. Paired t tests were used
      to compare pre- and post-PR changes in outcome variables. RESULTS: 45 patients
      with severe COPD (forced expiratory volume in 1 second [FEV(1)] 45% +/- 18% of
      predicted) participated in a total of 17.4 +/- 4.6 PR sessions. Significant
      improvements in 6MWT (49 +/- 59 m; p < .0001), MRC dyspnea score (-0.64 +/- 0.96
      units; p = .003) and CRQ score (10 +/- 18 units; p = .0007) were noted following
      PR. Patients whose pedometer-measured steps were within 20% of observed counted
      steps were included in the analysis. Pedometer counts increased by 33 +/- 149
      steps per hour worn after, as compared with before PR (p = .14). There was a
      significant inverse relationship between baseline pedometer counts and change in
      pedometer counts per hour post-PR (r = -.46; p = .001). Patients with low
      baseline activity levels had significant increases in pedometer activity (88 +/-
      30 counts per hour worn) and a greater reduction in MRC dyspnea score (-0.94 vs 
      0.29; p = .04) following PR, whereas those with higher baseline activity levels
      had a decrease in pedometer activity (-19 +/- 29 counts/hour; p = .015).
      CONCLUSIONS: A standard pedometer worn at the waist did not detect changes in
      lower extremity activity following PR. This negative finding occurred despite
      demonstrated improvements in dyspnea, exercise tolerance and quality of life
      measures. Although pedometers are inexpensive and easy to use, they may not be
      sensitive enough to be used routinely as an outcome measure for PR.

PMID- 19858352
TI  - PatientsLikeMe the case for a data-centered patient community and how ALS
      patients use the community to inform treatment decisions and manage pulmonary
      health.
AB  - What happens when patients go online to not only discuss health and daily living
      but to share detailed health data? PatientsLikeMe is an online platform where
      patients with life-altering conditions share structured information about
      symptoms, treatments, and outcomes, view individual and aggregated reports of
      these data, and discuss health and garner support on forums and through private
      messages. In this case study, we describe the components of this platform and how
      people with Amyotrophic lateral sclerosis have used the site to manage and
      improve pulmonary health. A qualitative analysis of forum content containing
      preset terms reveals patterns in use. As in other online communities, members of
      PatientsLikeMe offer one another support based on their own personal experience
      and advise each other on both medical issues and how to improve day-to-day life.
      Unique to this patient platform, members tailor questions and consults by
      referencing concrete data displayed for each patient member. PatientsLikeMe adds
      data into patient investigations on how to improve daily life and long term
      health outcomes.

PMID- 19858353
TI  - Mechanisms of exercise limitation and pulmonary rehabilitation for patients with
      neuromuscular disease.
AB  - Indications for exercise and pulmonary rehabilitation extend to neuromuscular
      diseases tough these conditions pose particular challenges given the associated
      skeletal muscle impairment and respiratory muscle dysfunction. These challenges
      are compounded by the variety of exercise prescriptions (aerobic, muscle
      strengthening, and respiratory muscle training) and the variety of neuromuscular
      disorders (muscular, motor neuron, motor nerve root, and neuromuscular
      transmission disorders). Studies support a level II evidence of effectiveness
      (i.e., likely to be effective) for a combination of aerobic exercise and
      strengthening exercises in muscular disorders, and for strengthening exercises in
      amyotrophic lateral sclerosis. The potential deleterious effects of work overload
      in the dystrophinopathies have not been confirmed in Becker muscular dystrophy.
      Adjunctive pharmacologic interventions (e.g., theophylline, steroids, PDE5
      inhibitors, creatine), training recommendations (e.g., interval or lower
      intensity training) and supportive techniques (e.g., noninvasive ventilation,
      neuromuscular electrical stimulation, and diaphragm pacing) may result in more
      effective training but require more study before formal recommendations can be
      made. The exercise prescription should include avoidance of inspiratory muscle
      training in hypercapnia or low vital capacity, and should match the desired
      outcome (e.g., extremity training for task-specific performance, exercise
      training to enhance exercise performance, respiratory muscle training where
      respiratory muscle involvement contributes to the impairment).

PMID- 19858354
TI  - Palliative sedation: welcome guidance on a controversial issue.

PMID- 19858355
TI  - European Association for Palliative Care (EAPC) recommended framework for the use
      of sedation in palliative care.
AB  - The European Association for Palliative Care (EAPC) considers sedation to be an
      important and necessary therapy in the care of selected palliative care patients
      with otherwise refractory distress. Prudent application of this approach requires
      due caution and good clinical practice. Inattention to potential risks and
      problematic practices can lead to harmful and unethical practice which may
      undermine the credibility and reputation of responsible clinicians and
      institutions as well as the discipline of palliative medicine more generally.
      Procedural guidelines are helpful to educate medical providers, set standards for
      best practice, promote optimal care and convey the important message to staff,
      patients and families that palliative sedation is an accepted, ethical practice
      when used in appropriate situations. EAPC aims to facilitate the development of
      such guidelines by presenting a 10-point framework that is based on the pre
      existing guidelines and literature and extensive peer review.

PMID- 19858356
TI  - An oily competition: role of beta subunit palmitoylation for Ca2+ channel
      modulation by fatty acids.

PMID- 19858357
TI  - The Ca2+ channel beta subunit determines whether stimulation of Gq-coupled
      receptors enhances or inhibits N current.
AB  - In superior cervical ganglion (SCG) neurons, stimulation of M(1) receptors
      (M(1)Rs) produces a distinct pattern of modulation of N-type calcium (N-) channel
      activity, enhancing currents elicited with negative test potentials and
      inhibiting currents elicited with positive test potentials. Exogenously applied
      arachidonic acid (AA) reproduces this profile of modulation, suggesting AA
      functions as a downstream messenger of M(1)Rs. In addition, techniques that
      diminish AA's concentration during M(1)R stimulation minimize N-current
      modulation. However, other studies suggest depletion of phosphatidylinositol-4,5
      bisphosphate during M(1)R stimulation suffices to elicit modulation. In this
      study, we used an expression system to examine the physiological mechanisms
      regulating modulation. We found the beta subunit (Ca(V)beta) acts as a molecular
      switch regulating whether modulation results in enhancement or inhibition. In
      human embryonic kidney 293 cells, stimulation of M(1)Rs or neurokinin-1 receptors
      (NK-1Rs) inhibited activity of N channels formed by Ca(V)2.2 and coexpressed with
      Ca(V)beta1b, Ca(V)beta3, or Ca(V)beta4 but enhanced activity of N channels
      containing Ca(V)beta2a. Exogenously applied AA produced the same pattern of
      modulation. Coexpression of Ca(V)beta2a, Ca(V)beta3, and Ca(V)beta4 recapitulated
      the modulatory response previously seen in SCG neurons, implying heterogeneous
      association of Ca(V)beta with Ca(V)2.2. Further experiments with mutated,
      chimeric Ca(V)beta subunits and free palmitic acid revealed that palmitoylation
      of Ca(V)beta2a is essential for loss of inhibition. The data presented here fit a
      model in which Ca(V)beta2a blocks inhibition, thus unmasking enhancement. Our
      discovery that the presence or absence of palmitoylated Ca(V)beta2a toggles M(1)R
      or NK-1R-mediated modulation of N current between enhancement and inhibition
      identifies a novel role for palmitoylation. Moreover, these findings predict that
      at synapses, modulation of N-channel activity by M(1)Rs or NK-1Rs will fluctuate
      between enhancement and inhibition based on the presence of palmitoylated
      Ca(V)beta2a.

PMID- 19858358
TI  - Orientation of palmitoylated CaVbeta2a relative to CaV2.2 is critical for slow
      pathway modulation of N-type Ca2+ current by tachykinin receptor activation.
AB  - The G(q)-coupled tachykinin receptor (neurokinin-1 receptor [NK-1R]) modulates N
      type Ca(2+) channel (Ca(V)2.2 or N channel) activity at two distinct sites by a
      pathway involving a lipid metabolite, most likely arachidonic acid (AA). In
      another study published in this issue (Heneghan et al. 2009. J. Gen Physiol.
      doi:10.1085/jgp.200910203), we found that the form of modulation observed depends
      on which Ca(V)beta is coexpressed with Ca(V)2.2. When palmitoylated Ca(V)beta2a
      is coexpressed, activation of NK-1Rs by substance P (SP) enhances N current. In
      contrast, when Ca(V)beta3 is coexpressed, SP inhibits N current. However,
      exogenously applied palmitic acid minimizes this inhibition. These findings
      suggested that the palmitoyl groups of Ca(V)beta2a may occupy an inhibitory site
      on Ca(V)2.2 or prevent AA from interacting with that site, thereby minimizing
      inhibition. If so, changing the orientation of Ca(V)beta2a relative to Ca(V)2.2
      may displace the palmitoyl groups and prevent them from antagonizing AA's
      actions, thereby allowing inhibition even in the presence of Ca(V)beta2a. In this
      study, we tested this hypothesis by deleting one (Bdel1) or two (Bdel2) amino
      acids proximal to the alpha interacting domain (AID) of Ca(V)2.2's I-II linker.
      Ca(V)betas bind tightly to the AID, whereas the rigid region proximal to the AID
      is thought to couple Ca(V)beta's movements to Ca(V)2.2 gating. Although
      Bdel1/beta2a currents exhibited more variable enhancement by SP, Bdel2/beta2a
      current enhancement was lost at all voltages. Instead, inhibition was observed
      that matched the profile of N-current inhibition from Ca(V)2.2 coexpressed with
      Ca(V)beta3. Moreover, adding back exogenous palmitic acid minimized inhibition of
      Bdel2/beta2a currents, suggesting that when palmitoylated Ca(V)beta2a is
      sufficiently displaced, endogenously released AA can bind to the inhibitory site.
      These findings support our previous hypothesis that Ca(V)beta2a's palmitoyl
      groups directly interact with an inhibitory site on Ca(V)2.2 to block N-current
      inhibition by SP.

PMID- 19858359
TI  - Closed-channel block of BK potassium channels by bbTBA requires partial
      activation.
AB  - Blockade of large-conductance Ca(2+)-activated K(+) (BK) channels by the bulky
      quaternary ammonium compound, N-(4-[benzoyl]benzyl)-N,N,N-tributylammonium
      (bbTBA), exhibits features consistent with blockade of both closed and open
      states. Here, we examine block of closed BK channels by bbTBA and how it may
      differ from block of open channels. Although our observations generally confirm
      earlier results, we describe three observations that are inconsistent with a
      model in which closed and open channels are equally accessible to blockade by
      bbTBA. First, block by bbTBA exhibits Ca(2+)-dependent features that are
      inconsistent with strictly state-independent block. Second, the steady-state
      voltage dependence of bbTBA block at negative potentials shows that any block of
      completely closed states either does not occur or is completely voltage
      independent. Third, determination of the fractional unblock by bbTBA at either
      low or high Ca(2+) reveals deviations from a model in which open- and closed
      state block is identical. The results support the view that bbTBA blockade of
      fully closed channels does not occur. We imagine two general types of
      explanation. First, a stronger voltage dependence of closed-channel block may
      minimize the contribution of closed-channel block at negative potentials. Second,
      voltage-dependent conformational changes among closed-channel states may permit
      block by bbTBA. The analysis supports the latter view, suggesting that bbTBA
      blockade of fully closed channels does not occur, but the ability of bbTBA to
      block a closed channel requires movement of one or more voltage sensors. Models
      in which block is coupled to voltage sensor movement can qualitatively account
      for (1) the ability of open-channel block to better fit block of conductance
      voltage curves at high Ca(2+); (2) the voltage dependence of fractional
      availability; and (3) the fractional unblock at different open probabilities. BK
      channels appear to undergo voltage-dependent conformational changes among closed
      states that are permissive for bbTBA block.

PMID- 19858360
TI  - Affinity for phosphatidylinositol 4,5-bisphosphate determines muscarinic agonist
      sensitivity of Kv7 K+ channels.
AB  - Kv7 K(+)-channel subunits differ in their apparent affinity for PIP(2) and are
      differentially expressed in nerve, muscle, and epithelia in accord with their
      physiological roles in those tissues. To investigate how PIP(2) affinity affects
      the response to physiological stimuli such as receptor stimulation, we exposed
      homomeric and heteromeric Kv7.2, 7.3, and 7.4 channels to a range of
      concentrations of the muscarinic receptor agonist oxotremorine-M (oxo-M) in a
      heterologous expression system. Activation of M(1) receptors by oxo-M leads to
      PIP(2) depletion through G(q) and phospholipase C (PLC). Chinese hamster ovary
      cells were transiently transfected with Kv7 subunits and M(1) receptors and
      studied under perforated-patch voltage clamp. For Kv7.2/7.3 heteromers, the
      EC(50) for current suppression was 0.44 +/- 0.08 microM, and the maximal
      inhibition (Inhib(max)) was 74 +/- 3% (n = 5-7). When tonic PIP(2) abundance was
      increased by overexpression of PIP 5-kinase, the EC(50) was shifted threefold to
      the right (1.2 +/- 0.1 microM), but without a significant change in Inhib(max)
      (73 +/- 4%, n = 5). To investigate the muscarinic sensitivity of Kv7.3 homomers,
      we used the A315T pore mutant (Kv7.3(T)) that increases whole-cell currents by 30
      fold without any change in apparent PIP(2) affinity. Kv7.3(T) currents had a
      slightly right-shifted EC(50) as compared with Kv7.2/7.3 heteromers (1.0 +/- 0.8
      microM) and a strongly reduced Inhib(max) (39 +/- 3%). In contrast, the dose
      response curve of homomeric Kv7.4 channels was shifted considerably to the left
      (66 +/- 8 nM), and Inhib(max) was slightly increased (81 +/- 6%, n = 3-4). We
      then studied several Kv7.2 mutants with altered apparent affinities for PIP(2) by
      coexpressing them with Kv7.3(T) subunits to boost current amplitudes. For the
      lower affinity (Kv7.2 (R463Q)/Kv7.3(T)) or higher affinity (Kv7.2
      (R463E)/Kv7.3(T)) channels, the EC(50) and Inhib(max) were similar to Kv7.4 or
      Kv7.3(T) homomers (0.12 +/- 0.08 microM and 79 +/- 6% [n = 3-4] and 0.58 +/- 0.07
      microM and 27 +/- 3% [n = 3-4], respectively). The very low-affinity Kv7.2
      (R452E, R459E, and R461E) triple mutant was also coexpressed with Kv7.3(T). The
      resulting heteromer displayed a very low EC(50) for inhibition (32 +/- 8 nM) and
      a slightly increased Inhib(max) (83 +/- 3%, n = 3-4). We then constructed a
      cellular model that incorporates PLC activation by oxo-M, PIP(2) hydrolysis,
      PIP(2) binding to Kv7-channel subunits, and K(+) current through Kv7 tetramers.
      We were able to fully reproduce our data and extract a consistent set of PIP(2)
      affinities.

PMID- 19858361
TI  - Theta bursts in the olfactory nerve paired with beta-adrenoceptor activation
      induce calcium elevation in mitral cells: a mechanism for odor preference
      learning in the neonate rat.
AB  - Odor preference learning in the neonate rat follows pairing of odor input and
      noradrenergic activation of beta-adrenoceptors. Odor learning is hypothesized to
      be supported by enhanced mitral cell activation. Here a mechanism for enhanced
      mitral cell signaling is described. Theta bursts in the olfactory nerve (ON)
      produce long-term potentiation (LTP) of glomerular excitatory postsynaptic
      potentials (EPSPs) and of excitatory postsynaptic currents (EPSCs) in the
      periglomerular (PG) and external tufted (ET) cells. Theta bursts paired with beta
      adrenoceptor activation significantly elevate mitral cell (MC) calcium.
      Juxtaglomerular inhibitory network depression by beta-adrenoceptor activation
      appears to increase calcium in MCs in response to theta burst stimulation.

PMID- 19858362
TI  - A novel strategy of transcription regulation by intragenic nucleosome ordering.
AB  - Numerous studies of chromatin structure showed that nucleosome free regions
      (NFRs) located at 5' gene ends contribute to transcription initiation regulation.
      Here, we determine the role of intragenic chromatin structure on gene expression
      regulation. We show that, along Saccharomyces cerevisiae genes, nucleosomes are
      highly organized following two types of architecture that depend only on the
      distance between the NFRs located at the 5' and 3' gene ends. In the first type,
      this distance constrains in vivo the positioning of n nucleosomes regularly
      organized in a "crystal-like" array. In the second type, this distance is such
      that the corresponding genes can accommodate either n or (n + 1) nucleosomes,
      thereby displaying two possible crystal-like arrays of n weakly compacted or n +
      1 highly compacted nucleosomes. This adaptability confers "bi-stable" properties
      to chromatin and is a key to its dynamics. Compared to crystal-like genes, bi
      stable genes present higher transcriptional plasticity, higher sensitivity to
      chromatin regulators, higher H3 turnover rate, and lower H2A.Z enrichment. The
      results strongly suggest that transcription elongation is facilitated by higher
      chromatin compaction. The data allow us to propose a new paradigm of
      transcriptional control mediated by the stability and the level of compaction of
      the intragenic chromatin architecture and open new ways for investigating
      eukaryotic gene expression regulation.

PMID- 19858363
TI  - Detection of nonneutral substitution rates on mammalian phylogenies.
AB  - Methods for detecting nucleotide substitution rates that are faster or slower
      than expected under neutral drift are widely used to identify candidate
      functional elements in genomic sequences. However, most existing methods consider
      either reductions (conservation) or increases (acceleration) in rate but not
      both, or assume that selection acts uniformly across the branches of a phylogeny.
      Here we examine the more general problem of detecting departures from the neutral
      rate of substitution in either direction, possibly in a clade-specific manner. We
      consider four statistical, phylogenetic tests for addressing this problem: a
      likelihood ratio test, a score test, a test based on exact distributions of
      numbers of substitutions, and the genomic evolutionary rate profiling (GERP)
      test. All four tests have been implemented in a freely available program called
      phyloP. Based on extensive simulation experiments, these tests are remarkably
      similar in statistical power. With 36 mammalian species, they all appear to be
      capable of fairly good sensitivity with low false-positive rates in detecting
      strong selection at individual nucleotides, moderate selection in 3-bp elements,
      and weaker or clade-specific selection in longer elements. By applying phyloP to
      mammalian multiple alignments from the ENCODE project, we shed light on patterns
      of conservation/acceleration in known and predicted functional elements,
      approximate fractions of sites subject to constraint, and differences in clade
      specific selection in the primate and glires clades. We also describe new
      "Conservation" tracks in the UCSC Genome Browser that display both phyloP and
      phastCons scores for genome-wide alignments of 44 vertebrate species.

PMID- 19858366
TI  - LKB1 and mammalian target of rapamycin as predictive factors for the anticancer
      efficacy of metformin.

PMID- 19858364
TI  - Genome-wide mapping of alternative splicing in Arabidopsis thaliana.
AB  - Alternative splicing can enhance transcriptome plasticity and proteome diversity.
      In plants, alternative splicing can be manifested at different developmental
      stages, and is frequently associated with specific tissue types or environmental
      conditions such as abiotic stress. We mapped the Arabidopsis transcriptome at
      single-base resolution using the Illumina platform for ultrahigh-throughput RNA
      sequencing (RNA-seq). Deep transcriptome sequencing confirmed a majority of
      annotated introns and identified thousands of novel alternatively spliced mRNA
      isoforms. Our analysis suggests that at least approximately 42% of intron
      containing genes in Arabidopsis are alternatively spliced; this is significantly
      higher than previous estimates based on cDNA/expressed sequence tag sequencing.
      Random validation confirmed that novel splice isoforms empirically predicted by
      RNA-seq can be detected in vivo. Novel introns detected by RNA-seq were
      substantially enriched in nonconsensus terminal dinucleotide splice signals.
      Alternative isoforms with premature termination codons (PTCs) comprised the
      majority of alternatively spliced transcripts. Using an example of an essential
      circadian clock gene, we show that intron retention can generate relatively
      abundant PTC(+) isoforms and that this specific event is highly conserved among
      diverse plant species. Alternatively spliced PTC(+) isoforms can be potentially
      targeted for degradation by the nonsense mediated mRNA decay (NMD) surveillance
      machinery or regulate the level of functional transcripts by the mechanism of
      regulated unproductive splicing and translation (RUST). We demonstrate that the
      relative ratios of the PTC(+) and reference isoforms for several key regulatory
      genes can be considerably shifted under abiotic stress treatments. Taken
      together, our results suggest that like in animals, NMD and RUST may be
      widespread in plants and may play important roles in regulating gene expression.

PMID- 19858367
TI  - Contralateral breast cancer in BRCA1/BRCA2 mutation carriers: the story of the
      other side.

PMID- 19858368
TI  - The hardest job in medicine.

PMID- 19858370
TI  - Call for clarity in the reporting of benefit associated with anticancer
      therapies.

PMID- 19858372
TI  - Molecular screening for Lynch syndrome: from bench to bedside.

PMID- 19858373
TI  - Darbepoetin alfa and history of thromboembolic events.

PMID- 19858375
TI  - If mammalian target of metformin indirectly is mammalian target of rapamycin,
      then the insulin-like growth factor-1 receptor axis will audit the efficacy of
      metformin in cancer clinical trials.

PMID- 19858377
TI  - To treat pelvic nodes or not: could the greater testicular scatter dose from
      whole pelvic fields confound results of prostate cancer trials?

PMID- 19858378
TI  - Bone marrow fibrosis and diagnosis of essential thrombocythemia.

PMID- 19858379
TI  - Phase III randomized comparison of gemcitabine versus gemcitabine plus
      capecitabine in patients with advanced pancreatic cancer.
AB  - PURPOSE: Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for
      advanced pancreatic cancer. This open-label study was designed to compare the
      overall survival (OS) of patients randomly assigned to GEM alone or GEM plus
      capecitabine (GEM-CAP). PATIENTS AND METHODS: Patients with previously untreated
      histologically or cytologically proven locally advanced or metastatic carcinoma
      of the pancreas with a performance status <or= 2 were recruited. Patients were
      randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival.
      Meta-analysis of published studies was also conducted. RESULTS: Between May 2002
      and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM
      CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1%
      v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95%
      CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS
      (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for
      OS benefit for GEM-CAP was consistent across different prognostic subgroups
      according to baseline stratification factors (stage and performance status) and
      remained after adjusting for these stratification factors (P = .077). Moreover,
      the meta-analysis of two additional studies involving 935 patients showed a
      significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98;
      P = .02) with no intertrial heterogeneity. CONCLUSION: On the basis of our trial
      and the meta-analysis, GEM-CAP should be considered as one of the standard first
      line options in locally advanced and metastatic pancreatic cancer.

PMID- 19858381
TI  - What does similarity mean in clinical trials?

PMID- 19858382
TI  - Solitary extramedullary plasmacytoma of the vocal cord in an adolescent.

PMID- 19858383
TI  - Quality of life supersedes the classic prognosticators for long-term survival in
      locally advanced non-small-cell lung cancer: an analysis of RTOG 9801.
AB  - PURPOSE: To determine the added value of quality of life (QOL) as a prognostic
      factor for overall survival (OS) in patients with locally advanced non-small-cell
      lung cancer (NSCLC) treated on Radiation Therapy Oncology Group RTOG-9801.
      PATIENTS AND METHODS: Two hundred forty-three patients with stage II/IIIAB NSCLC
      received induction paclitaxel and carboplatin (PC) and then concurrent weekly PC
      and hyperfractionated radiation (to 69.6 Gy). Patients were randomly assigned to
      amifostine (AM) or no AM during chemoradiotherapy. The following pretreatment
      factors were analyzed as prognostic factors for OS: Karnofsky performance status,
      stage, sex, age, race, marital status, histology, tumor location, hemoglobin,
      tobacco use, treatment arm (AM v no AM) and QOL scores (European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire C30 [QLQ-C30] and
      Lung Cancer 13 [LC-13]). A multivariate (MVA) Cox proportional hazards model was
      performed using a backwards selection process. RESULTS: Of the 239 analyzable
      patients, 91% had a baseline global QOL score. Median follow-up time was 59
      months for patients still alive and 17 months for all patients. Median baseline
      QLQ-C30 global QOL score was 66.7 on both treatment arms. Whether the global QOL
      score was treated as a dichotomized variable (based on the median score) or a
      continuous variable, all other variables fell out of the MVA for OS. Patients
      with a global QOL score less than 66.7 had an approximately 70% higher rate of
      death than patients with scores > or = 66.7 (P = .004). A 10-point higher
      baseline global QOL score corresponded to a decrease in the hazard of death by
      approximately 10% (P = .004). The other independent QOL predictors for OS were
      the QLQ-C30 physical functioning (P = .011) and LC-13 dyspnea scores (P = .012).
      CONCLUSION: In this analysis, baseline global QOL score replaced known prognostic
      factors as the sole predictor of long-term OS for patients with locally advanced
      NSCLC.

PMID- 19858385
TI  - Evaluating the combined effect of comorbidity and prostate-specific antigen
      kinetics on the risk of death in men after prostate-specific antigen recurrence.
AB  - PURPOSE: We examined whether time-dependent continuous prostate-specific antigen
      (PSA) velocity at recurrence was associated with all cause mortality (ACM)
      adjusting for comorbidity levels among men treated with definitive radiation
      therapy (RT) alone with or without androgen suppression therapy (AST) in the
      setting of a randomized controlled trial. PATIENTS AND METHODS: From 1995 to
      2001, 206 men with localized, unfavorable prostate cancer were randomly assigned
      to receive RT alone or RT and AST combined. Cox multivariate regression analysis
      was performed to evaluate the relationship between PSA velocity at recurrence and
      ACM, adjusting for known prostate cancer prognostic factors, including Adult
      Comorbidity Evaluation 27 comorbidity level. RESULTS: With a median follow-up of
      8.4 years, 89 biochemical recurrences and 74 ACM deaths occurred. Among all
      patients, higher PSA velocity was associated with increased ACM (hazard ratio
      [HR], 1.47; 95% CI, 1.07 to 1.44; P < .001) after adjusting for age, treatment
      arm, comorbidity score, and salvage AST. For 89 patients with biochemical
      recurrence, increasing PSA velocity at recurrence (HR, 1.60; 95% CI, 1.23 to
      2.09; P < or = .001) and moderate to severe comorbidity score (HR, 7.94; 95% CI,
      1.55 to 40.52; P = .01) were associated with increased ACM. PSA velocity at
      recurrence was associated with significantly higher risk of ACM among patients
      with no or minimal comorbidity (P < .001), but not moderate to severe comorbidity
      (P = .12). CONCLUSION: Rapid PSA velocity at recurrence is significantly
      associated with an increased risk of ACM among patients with no or minimal
      comorbidity but not moderate to severe comorbidity. These findings support
      judicious use of salvage AST, particularly in men with moderate to severe
      comorbidities, where prospective surveillance protocols are needed.

PMID- 19858384
TI  - Bladder cancer: narrowing the gap between evidence and practice.

PMID- 19858386
TI  - Bisphosphonate-related osteonecrosis of the jaw and left thumb.

PMID- 19858387
TI  - Changing the paradigm in conducting randomized clinical studies in advanced
      pancreatic cancer: an opportunity for better clinical development.

PMID- 19858389
TI  - Personalized cancer therapy with selective kinase inhibitors: an emerging
      paradigm in medical oncology.
AB  - Selective kinase inhibitors have emerged as an important class of anticancer
      agents, with demonstrated clinical efficacy and generally favorable toxicity
      profiles in several common disease settings where conventional treatments have
      previously provided only modest benefit. Consequently, a substantial effort is
      now underway to identify additional therapeutically relevant kinase targets and
      to develop and test inhibitors of those proteins in a variety of human
      malignancies. However, it has also become clear that the clinical benefit
      associated with these agents is typically limited to a subset of treated
      patients, who in many cases are defined by a specific genomic lesion within their
      tumor cells--frequently, an activating mutation within the gene encoding the
      target kinase. This discovery has prompted efforts to stratify patients before
      treatment with kinase inhibitors based on specific genomic biomarkers, with the
      goal of optimizing clinical outcomes through the effective personalization of
      treatment (ie, matching the right patients with the right therapies). With recent
      advances in our understanding of the relationship between tumor genotypes and
      cancer cell sensitivity to kinase inhibition, together with improved technologies
      for rapidly genotyping tumor biopsies for relevant lesions, the implementation of
      personalized cancer care with this exciting new class of inhibitors is now
      becoming a reality. In this review, we summarize recent developments in this
      area, and we highlight some of the logistical challenges posed by this emerging
      paradigm in medical oncology.

PMID- 19858388
TI  - Do male lymphoma survivors have impaired sexual function?
AB  - PURPOSE: Sexual function in male lymphoma survivors was examined and compared
      with that of age-matched controls. PATIENTS AND METHODS: This cross-sectional
      study included serum gonadal hormone levels (testosterone, sex hormone-binding
      globulin, luteinizing hormone [LH], and follicle-stimulating hormone) and
      responses to questionnaires assessing sexual function (Brief Sexual Function
      Inventory [BSFI]), socioeconomic factors, quality of life, emotional distress,
      and fatigue. The lymphoma group included 246 men < or = 50 years old at diagnosis
      who were diagnosed from 1980 to 2002 and treated at the Norwegian Radium
      Hospital. For each lymphoma survivor, two age-matched controls (n = 492) were
      drawn from a normative sample with BSFI scores. RESULTS: The lymphoma survivors
      had a mean age at survey of 47.4 years, the mean duration of follow-up was 14.8
      years, and 79% lived in committed relationships. All BSFI domain scores decreased
      significantly with age. Lymphoma survivors having low testosterone and/or
      elevated LH had lower BSFI scores than survivors with normal gonadal hormones.
      Multivariate analyses showed that increasing age, more emotional distress, poor
      physical health, and low testosterone and/or elevated LH were significantly
      associated with reduced sexual function within the lymphoma group. Lymphoma
      survivors had significantly lower BSFI domain scores than did controls on
      erection, ejaculation, and sexual satisfaction. CONCLUSION: Lymphoma survivors
      had significantly poorer sexual function than normative controls. It is unclear
      whether the abnormal hormone levels directly cause the reduced sexual function
      within the lymphoma group or if a mediating factor is involved, such as aging,
      emotional distress, or perceived health status.

PMID- 19858390
TI  - Tracheal glomangioma in a patient with asthma and chest pain.

PMID- 19858391
TI  - Phase II multicenter trial of anthracycline rechallenge with pegylated liposomal
      doxorubicin plus cyclophosphamide for first-line therapy of metastatic breast
      cancer previously treated with adjuvant anthracyclines.
AB  - PURPOSE: Anthracyclines are a component of breast cancer chemotherapy regimens in
      both adjuvant and metastatic settings. Anthracycline rechallenge for metastatic
      disease, for those previously exposed to adjuvant anthracyclines, may not be
      considered because of concerns about efficacy, tolerability, and cumulative
      cardiotoxicity. PATIENTS AND METHODS: This prospective, multicenter, single-arm,
      phase II trial examined the efficacy and safety of pegylated liposomal
      doxorubicin (PLD) 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) as first-line
      therapy, delivered every 3 weeks, in 70 patients who developed metastatic disease
      more than 12 months after completion of an adjuvant anthracycline-containing
      regimen. Seven patients discontinued treatment early and were excluded from the
      efficacy analysis. RESULTS: After a median of six cycles, the objective response
      rate was 38%. An additional 33% of patients achieved stable disease lasting more
      than 6 months, for an overall clinical benefit rate of 71%. The estimated median
      time to progression was 12.2 months. Median overall survival time was 16.5
      months. Clinical response was equally robust in patients with and without prior
      taxane exposure. Treatment was well tolerated. The most common grade 3 to 4
      toxicities were palmar-plantar erythrodysesthesia (PPE; 10%), dyspnea (9%), and
      neutropenia (9%). One (1.4%) of 70 patients discontinued treatment as a result of
      PPE. One patient (1.4%) experienced an infusion reaction requiring
      discontinuation. No symptomatic cardiac events were observed. CONCLUSION: PLD
      plus cyclophosphamide is effective and well tolerated in patients with metastatic
      breast cancer who have received prior adjuvant anthracycline-containing
      chemotherapy. The majority of patients experienced a clinical benefit without any
      significant impact on cardiac function.

PMID- 19858392
TI  - Quantitative PCR analysis for Bcl-2/IgH in a phase III study of Yttrium-90
      Ibritumomab Tiuxetan as consolidation of first remission in patients with
      follicular lymphoma.
AB  - PURPOSE The randomized First-Line Indolent Trial (FIT) was conducted in patients
      with advanced follicular lymphoma (FL), to evaluate the safety and efficacy of
      yttrium-90 ((90)Y) ibritumomab tiuxetan given as consolidation of complete or
      partial remission. This study of minimal residual disease was undertaken in
      parallel, to determine the rate of conversion from bcl-2 polymerase chain
      reaction (PCR) -detectable to -undetectable status and the corresponding effect
      on progression-free survival (PFS). PATIENTS AND METHODS Blood samples from 414
      patients ((90)Y-ibritumomab, n = 208; control, n = 206) were evaluated using real
      time quantitative polymerase chain reaction (RQ-PCR); 186 were found to have the
      bcl-2 rearrangement and were thus eligible for inclusion in the RQ-PCR analysis.
      Results Overall, 90% of treated patients converted from bcl-2 PCR-detectable to 
      undetectable disease status, compared with 36% in the control group. Treatment
      significantly prolonged median PFS in patients converting to bcl-2 PCR
      undetectable status (40.8 v 24.0 months in the control group; P < .01, hazard
      ratio [HR], 0.399). In patients who had bcl-2 PCR-detectable disease at random
      assignment, treatment significantly prolonged median PFS (38.4 v 8.2 months in
      the control group; P < .01, HR, 0.293). CONCLUSION Eradication of PCR-detectable
      disease occurred more frequently after treatment with (90)Y-ibritumomab tiuxetan
      and was associated with prolongation of PFS.

PMID- 19858393
TI  - Age-specific differences in oncogenic pathway dysregulation and anthracycline
      sensitivity in patients with acute myeloid leukemia.
AB  - PURPOSE: To define the biology driving the aggressive nature of acute myeloid
      leukemia (AML) in elderly patients. PATIENTS AND METHODS: Clinically annotated
      microarray data from 425 patients with newly diagnosed de novo AML from two
      publicly available data sets were analyzed after age-specific cohorts (young <or=
      45 years, n = 175; elderly >or= 55 years; n = 144) were prospectively identified.
      Gene expression analysis was conducted utilizing gene set enrichment analysis,
      and by applying previously defined and tested signature profiles reflecting
      dysregulation of oncogenic signaling pathways, altered tumor environment, and
      signatures of chemotherapy sensitivity. RESULTS: Elderly AML patients as expected
      had worse overall survival and event-free survival compared with younger
      patients. Analysis of oncogenic pathways revealed that older patients had higher
      probability of RAS, Src, and tumor necrosis factor (TNF) pathway activation (all
      P < .0001). Older patients were also less sensitive to anthracycline compared
      with younger patients with AML (P < .0001). Hierarchical clustering revealed that
      younger AML patients in cluster 2 had clinically worse survival, with high RAS,
      Src, and TNF pathway activation and in turn were less sensitive to anthracycline
      compared with patients in cluster 1. However, among elderly patients with AML,
      those in cluster 1 also demonstrated high RAS, Src, and TNF pathway activation
      but this did not translate into differences in survival or anthracycline
      sensitivity. CONCLUSION: AML in the elderly represents a distinct biologic entity
      characterized by unique patterns of deregulated signaling pathway variations that
      contributes to poor survival and anthracycline resistance. These insights should
      enable development and adjustments of clinically meaningful treatment strategies
      in the older patient population.

PMID- 19858394
TI  - VMP (Bortezomib, Melphalan, and Prednisone) is active and well tolerated in newly
      diagnosed patients with multiple myeloma with moderately impaired renal function,
      and results in reversal of renal impairment: cohort analysis of the phase III
      VISTA study.
AB  - PURPOSE To assess bortezomib plus melphalan and prednisone (VMP) and melphalan
      and prednisone (MP) in previously untreated patients with multiple myeloma (MM)
      with renal impairment enrolled on the phase III VISTA study, and to evaluate
      renal impairment reversibility. PATIENTS AND METHODS Patients received nine 6
      week cycles of VMP (bortezomib 1.3 mg/m(2), melphalan 9 mg/m(2), prednisone 60
      mg/m(2)) or MP. Patients with serum creatinine higher than 2 mg/dL were excluded.
      Results In the VMP/MP arms, 6%/4%, 27%/30%, and 67%/66% of patients had baseline
      glomerular filtration rate (GFR) of < or = 30, 31 to 50, and higher than 50
      mL/min, respectively. Response rates were higher and time to progression (TTP)
      and overall survival (OS) longer with VMP versus MP across renal cohorts.
      Response rates with VMP and TTP in both arms did not appear significantly
      different between patients with GFR < or = 50 or higher than 50 mL/min; OS
      appeared somewhat longer in patients with normal renal function in both arms.
      Renal impairment reversal (baseline GFR < 50 improving to > 60 mL/min) was seen
      in 49 (44%) of 111 patients receiving VMP versus 40 (34%) of 116 patients
      receiving MP. By multivariate analysis, younger age (< 75 years; P = .006) and
      less severe impairment (GFR > or = 30 mL/min; P = .027) were associated with
      higher reversal rates. In addition, treatment with VMP approached significance (P
      = .07). In both arms, rates of grade 4 and 5 adverse events (AEs) and serious AEs
      appeared higher in patients with renal impairment; with VMP, rates of
      discontinuations/bortezomib dose reductions due to AEs did not appear affected.
      CONCLUSION VMP is a feasible, active, and well-tolerated treatment option for
      previously untreated patients with MM with moderate renal impairment, resulting
      in 44% renal impairment reversal.

PMID- 19858395
TI  - Evidence-based approach to the introduction of positron emission tomography in
      ontario, Canada.
AB  - PURPOSE: The uptake of new health care technologies is usually driven by industry
      promotion, physician interest, patient demand, and institutional ability to
      acquire the technology. The introduction of positron emission tomography (PET)
      scanning in the province of Ontario, Canada, followed a different path. METHODS:
      The Ontario provincial government, through its Ministry of Health and Long-Term
      Care, commissioned a systematic review of the literature. When this found only
      weak evidence that PET has a positive impact on clinical outcomes, the Ministry
      introduced a provincial PET evaluation program to close the evidence gap.
      RESULTS: This article describes the challenges encountered establishing the PET
      evaluation program. These included the design and conduct of the initial clinical
      trials, the establishment of a PET cancer registry, standardizing how PET scans
      were performed and reported, and gaining acceptance by health professionals for
      the evaluative program. CONCLUSION: The proliferation of health technologies is a
      key driver of increasing health care costs. The Ontario approach to the
      introduction of PET is a model worth consideration by health systems seeking to
      ensure that they receive value for money based on a strong evidentiary base when
      introducing new health technologies.

PMID- 19858397
TI  - Consensus report of the national cancer institute clinical trials planning
      meeting on pancreas cancer treatment.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer
      mortality, despite significant improvements in diagnostic imaging and operative
      mortality rates. The 5-year survival rate remains less than 5% because of
      microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials
      Planning Meeting in pancreatic cancer was convened by the National Cancer
      Institute's Gastrointestinal Cancer Steering Committee to discuss the integration
      of basic and clinical knowledge in the design of clinical trials in PDAC. Major
      emphasis was placed on the enhancement of research to identify and validate the
      relevant targets and molecular pathways in PDAC, cancer stem cells, and the
      microenvironment. Emphasis was also placed on developing rational combinations of
      targeted agents and the development of predictive biomarkers to assist selection
      of patient subsets. The development of preclinical tumor models that are better
      predictive of human PDAC must be supported with wider availability to the
      research community. Phase III clinical trials should be implemented only if there
      is a meaningful clinical signal of efficacy and safety in the phase II setting.
      The emphasis must therefore be on performing well-designed phase II studies with
      uniform sets of basic entry and evaluation criteria with survival as a primary
      endpoint. Patients with either metastatic or locally advanced PDAC must be
      studied separately.

PMID- 19858396
TI  - Randomized phase II study of gemcitabine administered at a fixed dose rate or in
      combination with cisplatin, docetaxel, or irinotecan in patients with metastatic
      pancreatic cancer: CALGB 89904.
AB  - PURPOSE: The relative value of gemcitabine-based combination chemotherapy therapy
      and prolonged infusions of gemcitabine in patients with advanced pancreatic
      cancer remains controversial. We explored the efficacy and toxicity of
      gemcitabine administered at a fixed dose rate or in combination with cisplatin,
      docetaxel, or irinotecan in a multi-institutional, randomized, phase II study.
      PATIENTS AND METHODS: Patients with metastatic pancreatic cancer were randomly
      assigned to one of the following four regimens: gemcitabine 1,000 mg/m(2) on days
      1, 8, and 15 with cisplatin 50 mg/m(2) on days 1 and 15 (arm A); gemcitabine
      1,500 mg/m(2) at a rate of 10 mg/m(2)/min on days 1, 8, and 15 (arm B);
      gemcitabine 1,000 mg/m(2) with docetaxel 40 mg/m(2) on days 1 and 8 (arm C); or
      gemcitabine 1,000 mg/m(2) with irinotecan 100 mg/m(2) on days 1 and 8 (arm D).
      Patients were observed for response, toxicity, and survival. Results Two hundred
      fifty-nine patients were enrolled onto the study, of whom 245 were eligible and
      received treatment. Anticipated rates of myelosuppression, fatigue, and expected
      regimen-specific toxicities were observed. The overall tumor response rates were
      12% to 14%, and the median overall survival times were 6.4 to 7.1 months among
      the four regimens. CONCLUSION: Gemcitabine/cisplatin, fixed dose rate
      gemcitabine, gemcitabine/docetaxel, and gemcitabine/irinotecan have similar
      antitumor activity in metastatic pancreatic cancer. In light of recent negative
      randomized studies directly comparing several of these regimens with standard
      gemcitabine, none of these approaches can be recommended for routine use in
      patients with this disease.

PMID- 19858398
TI  - Association of molecular markers with toxicity outcomes in a randomized trial of
      chemotherapy for advanced colorectal cancer: the FOCUS trial.
AB  - PURPOSE: Predicting efficacy and toxicity could potentially allow
      individualization of cancer therapy. We investigated putative pharmacogenetic
      markers of chemotherapy toxicity in a large randomized trial. PATIENTS,
      MATERIALS, AND METHODS: Patients were randomly assigned to different sequences of
      chemotherapy for advanced colorectal cancer. First-line therapy was fluorouracil
      (FU), irinotecan/FU (IrFU) or oxaliplatin/FU (OxFU). Patients allocated first
      line FU had planned second-line irinotecan alone, IrFU, or OxFU. The primary
      toxicity outcome measure was toxicity-induced delay or dose reduction; the
      secondary outcome was Common Terminology Criteria of Adverse Events grade >or= 3
      toxicity. DNA was analyzed in 1,188 patients; 1,036 were assessable for the
      primary outcome, including 688 treated with FU, 270 with IrFU (first or second
      line), 280 with OxFU (first or second line), 184 with irinotecan alone, and 454
      with any irinotecan-containing regimen. Ten polymorphisms were assessed:
      thymidylate synthase-enhancer region (TYMS-ER), thymidylate synthase 1494 (TYMS
      1494), dihydropyrimidine dehydrogenase (DPYD), methylenetetrahydrofolate
      reductase (MTHFR), mutL homolog 1 (MLH1), UDP glucuronyltransferase (UGT1A1), ATP
      binding cassette group B gene 1 (ABCB1), x-ray cross-complementing group 1
      (XRCC1), glutathione-S-transferase P1 (GSTP1), and excision repair cross
      complementing gene 2 (ERCC2). Results Using the primary outcome measure, no
      polymorphism was significantly associated (P < .01) with the toxicity of any
      regimen or with the difference in toxicity of IrFU or OxFU versus FU alone.
      Trends (of doubtful significance) were seen for associations of XRCC1, ERCC2, and
      GSTP1 with toxicity during irinotecan regimens: XRCC1, primary end point, any
      irinotecan-containing regimen (P = .045); ERCC2, secondary end point, irinotecan
      alone (P = .003); GSTP1, secondary end point; IrFU (P = .039); and irinotecan
      alone (P = .05). There was no evidence of association of UGT1A1*28 with
      irinotecan toxicity. CONCLUSION: These results do not support the routine
      clinical use of the evaluated polymorphisms, including UGT1A1*28. Further
      investigation of XRCC1, ERCC2, and GSTP1 as potential predictors of irinotecan
      toxicity is warranted.

PMID- 19858399
TI  - Dose finding and early efficacy study of gemcitabine plus capecitabine in
      combination with bevacizumab plus erlotinib in advanced pancreatic cancer.
AB  - PURPOSE: This study evaluated safety and efficacy of chemotherapy (gemcitabine
      plus capecitabine) plus bevacizumab/erlotinib in advanced pancreatic cancer
      because dual epidermal growth factor receptor/vascular endothelial growth factor
      blockade has a rational biologic basis in this malignancy. PATIENTS AND METHODS:
      Patients with untreated, unresectable, locally advanced or metastatic pancreatic
      carcinoma were enrolled onto one of the following four sequential dose levels
      (DLs) of escalating capecitabine doses (days 1 to 21): DL1, 910 mg/m(2); DL2,
      1,160 mg/m(2); DL3, 1,400 mg/m(2); or DL4, 1,660 mg/m(2). Doses of coadministered
      gemcitabine (1,000 mg/m(2) on days 1, 8, and 15), bevacizumab (5 mg/kg on days 1
      and 15), and erlotinib (100 mg/d) every 28 days (up to six cycles) were fixed.
      Using a 3+3 study design, dose-limiting toxicity (DLT) was assessed in cycle 1.
      Results Twenty assessable patients were enrolled (DL1, n = 8; DL2, n = 3; DL3, n
      = 6; and DL4, n = 3); 97 cycles were administered. Median age was 63 years
      (range, 33 to 77 years), and male-to-female ratio was 10:10. Performance status
      was 0 and 1 in two and 17 patients, respectively; and nine and 11 patients had
      locally advanced and metastatic disease, respectively. DLT occurred in one
      patient at DL1 (grade 3 epistaxis) and two patients at DL4 (grade 3 diarrhea and
      grade 3 skin rash > 7 days). Common grade 3 and 4 toxicities (10% to 20%) were
      diarrhea, hand-foot syndrome, stomatitis, and skin rash. Grade 3 lethargy and
      grade 3 or 4 neutropenia occurred in 40% and 45% of patients, respectively. No GI
      perforation, grade 3 GI hemorrhage/hypertension, or pneumonitis occurred. Ten
      partial responses were observed. Median overall and progression-survival times
      (all patients) were 12.5 and 9.0 months, respectively. CONCLUSION: The maximum
      tolerated dose of capecitabine was 1,660 mg/m(2). The recommended capecitabine
      dose in this cytotoxic doublet/biologic doublet regimen is 1,440 mg/m(2); this
      regimen is under evaluation in an ongoing phase II study.

PMID- 19858400
TI  - Prognostic and predictive value of HER2 extracellular domain in metastatic breast
      cancer treated with lapatinib and paclitaxel in a randomized phase III study.
AB  - PURPOSE: The HER2 extracellular domain (ECD) is enzymatically cleaved from the
      cell membrane. Shed ECD in serum has been studied as both prognostic and
      predictive markers. Lapatinib is a dual inhibitor of HER2 and epidermal growth
      factor receptor kinases. We examined the prognostic and predictive role of HER2
      ECD in a randomized trial of paclitaxel with placebo or lapatinib in women with
      HER2-negative or -unknown breast cancer. PATIENTS AND METHODS: Patients (n = 579)
      with newly diagnosed metastatic breast cancer (MBC) were randomly assigned to
      paclitaxel with placebo or lapatinib. HER2 status was determined centrally. ECD
      was centrally measured by enzyme linked immunoassay in available samples at
      baseline (b; n = 472), week 9, and every 12 weeks thereafter. Results were
      correlated to overall response rate (ORR) and progression-free survival (PFS).
      RESULTS: Elevated baseline ECD (bECD) levels (>or= 16 ng/mL) did not predict HER2
      tumor status (sensitivity, 62%; specificity, 75%). In HER2-negative tumors,
      elevated bECD was not correlated with improved efficacy for lapatinib plus
      paclitaxel versus placebo plus paclitaxel (ORR: odds ratio, 1.6; 95% CI, 0.1 to
      3.8; P = .365; PFS: hazard ratio, 0.94; 95% CI, 0.60 to 1.47; P = .797). ECD
      levels tended to decrease over time when bECD was elevated. ECD conversion from
      low to high was associated with worse PFS. Converting from high to low was
      associated with a better PFS. A consistently low ECD level had better PFS than a
      consistently elevated ECD. All associations were found to be independent of
      lapatinib. CONCLUSION: HER2 bECD does not predict lapatinib benefit in patients
      with HER2-negative MBC. Changes in ECD status correlates with patient outcome
      regardless of treatment given. Measuring HER2 ECD is not currently recommended
      for predicting benefit to lapatinib.

PMID- 19858401
TI  - Prospective study of prostate tumor angiogenesis and cancer-specific mortality in
      the health professionals follow-up study.
AB  - PURPOSE: Tumor growth requires the development of independent vascular networks
      that are often primitive in morphology and function. We examined whether
      microvessel morphology contributes to the considerable biologic heterogeneity of
      prostate cancer. METHODS: We evaluated microvessel morphology as a predictor of
      prostate cancer mortality among 572 men in the Health Professionals Follow-Up
      Study diagnosed with cancer during 1986 to 2000. We immunostained prostatectomy
      tumor block sections for endothelial marker CD34 and assessed microvessel
      density, vessel size (area and diameter), and irregularity of vessel lumen using
      image analysis. Proportional hazards models were used to assess microvessel
      density and morphology in relation to lethal prostate cancer. RESULTS: Poorly
      differentiated tumors exhibited greater microvessel density, greater irregularity
      of the vessel lumen, and smaller vessels. During 20 years of follow-up, 44 men
      developed bone metastases or died of cancer. Men with tumors exhibiting the
      smallest vessel diameter, based on quartiles, were 6.0 times more likely (95% CI,
      1.8 to 20.0) to develop lethal prostate cancer. Men with the most irregularly
      shaped vessels were 17.1 times more likely (95% CI, 2.3 to 128) to develop lethal
      disease. Adjusting for Gleason grade and prostate-specific antigen levels did not
      qualitatively change the results. Microvessel density was not linked to cancer
      specific mortality after adjusting for clinical factors. CONCLUSION: Aggressive
      tumors form vessels that are primitive in morphology and function, with
      consequences for metastases. Vascular size and irregularity reflect the
      angiogenic potential of prostate cancer and may serve as biomarkers to predict
      prostate cancer mortality several years after diagnosis.

PMID- 19858402
TI  - Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers.
AB  - PURPOSE: To estimate the risk for contralateral breast cancer in members of BRCA1
      and BRCA2-positive families and to determine predictive risk factors. PATIENTS
      AND METHODS: A retrospective, multicenter, cohort study was performed from 1996
      until 2008 and comprised 2,020 women with unilateral breast cancer (index
      patients, n = 978; relatives, n = 1.42) from 978 families who had a BRCA1 or
      BRCA2 mutation. Cox regression analysis was applied to assess the association of
      age at first breast cancer with time from first to contralateral breast cancer,
      stratified by the affected BRCA gene. RESULTS: The cumulative risk for
      contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI,
      38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members
      of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold)
      higher risk of contralateral breast cancer than members of families with BRCA2
      mutations. Younger age at first breast cancer was associated with a significantly
      higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a
      trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95%
      CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40
      years of age at first breast cancer developed contralateral breast cancer,
      compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50
      years of age at first breast cancer. CONCLUSION: Contralateral breast cancer risk
      depends on age at first breast cancer and on the affected BRCA gene, and this
      risk should be considered in treatment planning.

PMID- 19858403
TI  - Health-related quality of life in long-term survivors of testicular cancer.
AB  - PURPOSE: A growing number of patients with testicular cancer (TC) become long
      term survivors. As a consequence, quality-of-life (QOL) issues become
      increasingly important. The objective of this study was to investigate QOL among
      Danish TC survivors. METHODS: A long-term follow-up assessment of all patients
      with TC treated at Aarhus University Hospital in Denmark between 1990 and 2000
      was conducted. A total of 401 survivors (response rate, 66%) completed
      questionnaires concerning QOL (European Organisation for Research and Treatment
      of Cancer Quality of Life Questionnaire C30), depression (Beck Depression
      Inventory-II), fatigue (Multidimensional Fatigue Inventory-20), and health
      related issues such as neurotoxic symptoms and Raynaud-like phenomena. On the
      basis of their treatment, participants were categorized as having received
      surveillance, radiotherapy, or chemotherapy. RESULTS: QOL among patients with TC
      was equal to that of men from the general population. Although patients who
      received chemotherapy reported higher levels of peripheral sensory neuropathy,
      ototoxicity, and Raynaud-like phenomena, treatment strategies were generally
      unrelated to QOL and depressive symptoms. CONCLUSION: Overall, the patients in
      this study reported high levels of QOL. The results suggest that patients treated
      for TC should be informed about the anticipated good post-therapeutic QOL and the
      low risk of psychosocial and physical long-term effects.

PMID- 19858404
TI  - In situ cytotoxic and memory T cells predict outcome in patients with early-stage
      colorectal cancer.
AB  - PURPOSE: Many patients who present with early-stage colorectal cancer
      (International Union Against Cancer TNM stages I and II) are nevertheless at high
      risk of relapse. We hypothesized that intratumoral immune reaction could
      influence their prognosis. PATIENTS AND METHODS: The intratumoral immune reaction
      was investigated in 29 tumors by large-scale real-time polymerase chain reaction.
      Cytotoxic (CD8) and memory (CD45RO) T cells were quantified by
      immunohistochemical analyses of tissue microarrays from the center (CT) and the
      invasive margin (IM) of the 602 tumors from two independent cohorts. The results
      were correlated with tumor recurrence and patient survival. RESULTS: Patients
      with a strong infiltration of CD45RO(+) cells in the tumor exhibited an increased
      expression of T-helper 1 and cytotoxicity-related genes. Densities of CD45RO(+)
      and CD8(+) cells in tumor regions (CT/IM) classified the patients into four
      distinct prognostic groups based on the presence of high density of each marker
      in each tumor region. The four groups were associated with dramatic differences
      in disease-free, disease-specific, and overall survival (all P < .0001). Five
      years after diagnosis, only 4.8% (95% CI, 0.6% to 8.8%) of patients with high
      densities of CD8(+) plus CD45RO(+) cells had tumor recurrence, and 86.2% (CI,
      79.4% to 93.6%) survived. In contrast, the tumor recurred in 75% (95% CI, 17% to
      92.5%) of patients with low densities of these cells, and only 27.5% (95% CI,
      10.5% to 72%) survived (all P < .0001). Multivariate analyses showed that the
      immune criteria had independent effects on the rates of complete remission and
      survival. CONCLUSION: The combined analysis of CD8(+) plus CD45RO(+) cells in
      specific tumor regions could provide a useful criterion for the prediction of
      tumor recurrence and survival in patients with early-stage colorectal cancer.

PMID- 19858405
TI  - Efficacy of spironolactone therapy in patients with true resistant hypertension.
AB  - The role of spironolactone in resistant hypertension management is unclear. The
      aim of this prospective trial was to evaluate the antihypertensive effect of
      spironolactone in patients with true resistant hypertension diagnosed by
      ambulatory blood pressure monitoring. A total of 175 patients had clinical and
      complementary exams obtained at baseline and received spironolactone in doses of
      25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after
      a median interval of 7 months. Paired Student t test was used to assess
      differences in blood pressure before and during spironolactone administration,
      and multivariate analysis adjusted for age, sex, and number of antihypertensive
      drugs to assess the predictors of blood pressure fall. There were mean reductions
      of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood
      pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; P<0.001). Office systolic blood
      pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled
      ambulatory blood pressure was reached in 48% of patients. Factors associated with
      better response were higher waist circumference, lower aortic pulse wave
      velocity, and lower serum potassium. No association with plasma aldosterone or
      aldosterone:renin ratio was found. Adverse effects were observed in 13 patients
      (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients
      after a median of 15 months confirmed the persistence of the spironolactone
      effect. In conclusion, spironolactone administration to true resistant
      hypertensive patients is safe and effective in decreasing blood pressure,
      especially in those with abdominal obesity and lower arterial stiffness. Its
      addition to an antihypertensive regimen as the fourth or fifth drug is
      recommended.

PMID- 19858406
TI  - Pressure-induced renal injury in angiotensin II versus norepinephrine-induced
      hypertensive rats.
AB  - The susceptibility to renal perfusion pressure (RPP)-induced renal injury was
      investigated in angiotensin II (Ang II)- versus norepinephrine (NE)-infused
      hypertensive rats. To determine the magnitude of RPP-induced injury, Sprague
      Dawley rats fed a 4% salt diet were instrumented with a servocontrolled aortic
      balloon occluder positioned between the renal arteries to maintain RPP to the
      left kidney at baseline levels whereas the right kidney was exposed to elevated
      RPP during a 2-week infusion of Ang II IV (25 ng/kg per minute), NE IV (0.5, 1.0,
      and 2.0 microg/kg per minute on days 1, 2, and 3 to 14, respectively), or saline
      IV (sham rats). Over the 14 days of Ang II infusion, RPP averaged 161.5+/-8.0 mm
      Hg to uncontrolled kidneys and 121.9+/-2.0 mm Hg to servocontrolled kidneys. In
      NE-infused rats, RPP averaged 156.3+/-3.0 mm Hg to uncontrolled kidneys and
      116.9+/-2.0 mm Hg to servocontrolled kidneys. RPP averaged 111.1+/-1.0 mm Hg to
      kidneys of sham rats. Interlobular arterial injury and juxtamedullary
      glomerulosclerosis were largely RPP dependent in both models of hypertension.
      Superficial cortical glomerulosclerosis was greater and RPP dependent in NE-
      versus Ang II-infused rats, which was primarily independent of RPP. Outer
      medullary tubular necrosis and interstitial fibrosis were also primarily RPP
      dependent in both models of hypertension; however, the magnitude of injury was
      exacerbated in Ang II-infused rats. We conclude that elevated RPP is the dominant
      cause of renal injury in both NE- and Ang II-induced hypertensive rats and that
      underlying neurohumoral factors in these models of hypertension alter the pattern
      and magnitude of RPP-induced renal injury.

PMID- 19858407
TI  - Validation of a case definition to define hypertension using administrative data.
AB  - We validated the accuracy of case definitions for hypertension derived from
      administrative data across time periods (year 2001 versus 2004) and geographic
      regions using physician charts. Physician charts were randomly selected in rural
      and urban areas from Alberta and British Columbia, Canada, during years 2001 and
      2004. Physician charts were linked with administrative data through unique
      personal health number. We reviewed charts of approximately 50 randomly selected
      patients >35 years of age from each clinic within 48 urban and 16 rural family
      physician clinics to identify physician diagnoses of hypertension during the
      years 2001 and 2004. The validity indices were estimated for diagnosed
      hypertension using 3 years of administrative data for the 8 case-definition
      combinations. Of the 3,362 patient charts reviewed, the prevalence of
      hypertension ranged from 18.8% to 33.3%, depending on the year and region
      studied. The administrative data hypertension definition of "2 claims within 2
      years or 1 hospitalization" had the highest validity relative to the other
      definitions evaluated (sensitivity 75%, specificity 94%, positive predictive
      value 81%, negative predictive value 92%, and kappa 0.71). After adjustment for
      age, sex, and comorbid conditions, the sensitivities between regions, years, and
      provinces were not significantly different, but the positive predictive value
      varied slightly across geographic regions. These results provide evidence that
      administrative data can be used as a relatively valid source of data to define
      cases of hypertension for surveillance and research purposes.

PMID- 19858408
TI  - Ablation of transient receptor potential vanilloid 1 abolishes endothelin-induced
      increases in afferent renal nerve activity: mechanisms and functional
      significance.
AB  - Endothelin 1 (ET-1) and its receptors, ETA and ETB, play important roles in
      regulating renal function and blood pressure, and these components are expressed
      in sensory nerves. Activation of transient receptor potential vanilloid (TRPV) 1
      channels expressed in sensory nerves innervating the renal pelvis enhances
      afferent renal nerve activity (ARNA), diuresis, and natriuresis. We tested the
      hypothesis that ET-1 increases ARNA via activation of ETB, whereas ETA
      counterbalances ETB in wild-type (WT) but not TRPV1-null mutant mice. ET-1 alone
      or with BQ123, an ETA antagonist, perfused into the left renal pelvis increased
      ipsilateral ARNA in WT but not in TRPV1-null mutant mice, and ARNA increases were
      greater in the latter. [Ala1, 3,11,15]-endothelin 1, an ETB agonist, increased
      ARNA that was greater than that induced by ET-1 in WT mice only. [Ala1, 3,11,15]
      endothelin 1-induced increases in ARNA were abolished by chelerythrine, a protein
      kinase C inhibitor, but not by H89, a protein kinase A inhibitor. Chelerythrine,
      H89, and BQ788, an ETB antagonist, did not affect ARNA triggered by capsaicin in
      WT mice. Substance P release from the renal pelvis was increased by [Ala1,
      3,11,15]-endothelin 1 in WT mice only, and the increase was abolished by
      chelerythrine but not by H89. Chelerythrine, H89, and BQ788 did not affect
      capsaicin-induced substance P release. Our data show that ET1 increases ARNA via
      activation of ETB, whereas ETA counterbalances ETB in WT but not in TRPV1-null
      mutant mice, suggesting that TRPV1 mediates ETB-dependent increases in ARNA,
      diuresis, and natriuresis possibly via the protein kinase C pathway.

PMID- 19858410
TI  - Radiation risk from pediatric cardiac catheterization: friendly fire on children
      with congenital heart disease.

PMID- 19858409
TI  - Protection of angiotensin II-induced vascular hypertrophy in vascular smooth
      muscle-targeted receptor activity-modifying protein 2 transgenic mice.
AB  - The vasodilator and vascular regulatory peptide adrenomedullin (AM), a member of
      the calcitonin gene-related peptide family of peptides, is predicted to play a
      pivotal protective role in cardiovascular dysfunction. The principle AM (AM1)
      receptor is composed of a G protein-linked calcitonin receptor-like receptor and
      a receptor activity-modifying protein (receptor activity-modifying protein 2).
      There is little knowledge of the receptors via which AM acts in diseases. Using
      smooth muscle-targeted receptor activity-modifying protein 2 transgenic mice with
      increased vascular density of functional AM1 receptors, we demonstrate that
      receptor activity-modifying protein 2 transgenic mice are not protected against
      angiotensin II-induced hypertension or cardiac hypertrophy. However, vascular
      hypertrophy, together with vascular cell adhesion molecule 1 and monocyte
      chemotactic protein 1 expression, is significantly reduced in the aortic walls of
      transgenic mice, as determined by histological techniques. This indicates that
      the AM1 vascular smooth muscle receptor can mediate local protection in vivo.
      This is supported by proliferation studies in cultured smooth muscle cells. By
      comparison, levels of hypotension and inflammation in a shock model were similar
      to those in wild-type mice. Thus, a role of the AM1 receptor in the vasoactive
      component could not be detected, and evidence is provided to show that the
      hypotensive response to AM is subject to desensitization in vivo. The finding
      that the vascular smooth muscle AM1 receptor acts at a local level to protect
      against hypertension-induced vascular hypertrophy and inflammation provides
      evidence that targeting this receptor may be a beneficial therapeutic approach.

PMID- 19858411
TI  - Early cardiac resynchronization therapy and reverse remodeling in patients with
      mild heart failure: is it time?

PMID- 19858412
TI  - gamma-H2AX foci as a biomarker for patient X-ray exposure in pediatric cardiac
      catheterization: are we underestimating radiation risks?
AB  - BACKGROUND: A better knowledge of patient x-ray dose and the associated radiation
      risk in pediatric interventional cardiology is warranted in view of the extensive
      use of x-rays and the higher radiosensitivity of children. In the present study,
      gamma-H2AX foci were used as a biomarker for radiation-induced effects. Patient
      specific dose was assessed and radiation risks were estimated according to the
      linear-no-threshold model, commonly used in radiation protection, and the gamma
      H2AX foci data. METHODS AND RESULTS: In 49 pediatric patients (median age, 0.75
      years) with congenital heart disease who underwent cardiac catheterization
      procedures, blood samples were taken before and shortly after the procedure.
      gamma-H2AX foci were determined in peripheral blood T lymphocytes. In each
      patient, a net increase in gamma-H2AX foci, representing DNA double-strand breaks
      induced by interventional x-rays, was observed. In addition, a patient-specific
      Monte Carlo simulation of the procedure was performed, resulting in individual
      blood, organ, and tissue doses. Plotting of gamma-H2AX foci versus blood dose
      indicated a low-dose hypersensitivity. Median effective doses calculated
      according to the International Commission on Radiological Protection 60 and 103
      publications are 5.6 and 6.4 mSv, respectively. The lifetime-attributable risk of
      cancer mortality was calculated from the linear-no-threshold model and the gamma
      H2AX foci data. This resulted in lifetime-attributable risk values of 1% and 4%,
      respectively, for the patient population under study. CONCLUSIONS: gamma-H2AX
      foci as a biomarker for DNA damage indicate that radiation risk estimates
      according to the linear-no-threshold hypothesis are possibly underestimates.
      Great care should be taken to minimize and optimize patient radiation exposure.

PMID- 19858413
TI  - Volumetric intravascular ultrasound analysis of Paclitaxel-eluting and bare metal
      stents in acute myocardial infarction: the harmonizing outcomes with
      revascularization and stents in acute myocardial infarction intravascular
      ultrasound substudy.
AB  - BACKGROUND: Vascular responses to drug-eluting stents in ST-segment elevation
      myocardial infarction are unknown. In the prospective, multicenter Harmonizing
      Outcomes With Revascularization and Stents in Acute Myocardial Infarction
      (HORIZONS-AMI) trial, patients with ST-segment elevation myocardial infarction
      within 12 hours of symptom onset were randomized 3:1 to TAXUS EXPRESS paclitaxel
      eluting stents (PES) or EXPRESS bare metal stents (BMS). METHODS AND RESULTS: A
      formal intravascular ultrasound substudy enrolled 464 patients with baseline and
      13-month follow-up imaging at 36 centers. Overall, 446 lesions in 402 patients
      were suitable for standard qualitative and quantitative analyses, which were
      performed at an independent blinded core laboratory. The primary prespecified end
      point was the in-stent percent net volume obstruction at follow-up. Median stent
      length measured 23.4 mm (first and third quartiles, 18.5 and 31.9 mm). PES
      compared with BMS significantly reduced 13-month percent net volume obstruction
      (6.5% [first and third quartiles, 2.2% and 10.8%] versus 15.6% [first and third
      quartiles, 7.2% and 28.8%]; P<0.0001). PES compared with BMS also resulted in
      more late-acquired stent malapposition (29.6% versus 7.9%; P=0.0005) resulting
      from positive vessel remodeling. Plaque and/or thrombus protrusion through stent
      struts was initially present in 70.4% of PES and 64.8% of BMS; all resolved
      during follow-up. New aneurysm formation, stent fracture, and subclinical
      thrombus were uncommon, although seen only in PES. CONCLUSIONS: PES compared with
      BMS significantly reduce neointimal hyperplasia in patients with ST-segment
      elevation myocardial infarction but also result in a high frequency of late
      acquired stent malapposition as a result of positive vessel remodeling. Ongoing
      long-term follow-up is required to establish the clinical significance of these
      findings. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00433966.

PMID- 19858414
TI  - Three-year outcomes after sirolimus-eluting stent implantation for unprotected
      left main coronary artery disease: insights from the j-Cypher registry.
AB  - BACKGROUND: Long-term outcomes after stenting of an unprotected left main
      coronary artery (ULMCA) with drug-eluting stents have not been addressed
      adequately despite the growing popularity of this procedure. METHODS AND RESULTS:
      j-Cypher is a multicenter prospective registry of consecutive patients undergoing
      sirolimus-eluting stent implantation in Japan. Among 12 824 patients enrolled in
      the j-Cypher registry, the unadjusted mortality rate at 3 years was significantly
      higher in patients with ULMCA stenting (n=582) than in patients without ULMCA
      stenting (n=12 242; 14.6% versus 9.2%, respectively; P<0.0001); however, there
      was no significant difference between the 2 groups in the adjusted risk of death
      (hazard ratio 1.23, 95% confidence interval 0.95 to 1.60, P=0.12). Among 476
      patients whose ULMCA lesions were treated exclusively with a sirolimus-eluting
      stent, patients with ostial/shaft lesions (n=96) compared with those with
      bifurcation lesions (n=380) had a significantly lower rate of target-lesion
      revascularization for the ULMCA lesions (3.6% versus 17.1%, P=0.005), with
      similar cardiac death rates at 3 years (9.8% versus 7.6%, P=0.41). Among patients
      with bifurcation lesions, patients with stenting of both the main and side
      branches (n=119) had significantly higher rates of cardiac death (12.2% versus
      5.5%; P=0.02) and target-lesion revascularization (30.9% versus 11.1%; P<0.0001)
      than those with main-branch stenting alone (n=261). CONCLUSIONS: The higher
      unadjusted mortality rate of patients undergoing ULMCA stenting with a sirolimus
      eluting stent did not appear to be related to ULMCA treatment itself but rather
      to the patients' high-risk profile. Although long-term outcomes in patients with
      ostial/shaft ULMCA lesions were favorable, outcomes in patients with bifurcation
      lesions treated with stenting of both the main and side branches appeared
      unacceptable.

PMID- 19858415
TI  - High levels of acetylated low-density lipoprotein uptake and low tyrosine kinase
      with immunoglobulin and epidermal growth factor homology domains-2 (Tie2)
      promoter activity distinguish sinusoids from other vessel types in murine bone
      marrow.
AB  - BACKGROUND: The bone marrow contains a variety of blood vessels that have
      different functions in bone marrow maintenance and hematopoiesis. Arterioles
      control the flow of blood into bone marrow compartments, and sinusoids serve as a
      conduit to the bloodstream and as niches for megakaryocyte development. Most
      studies of bone marrow vasculature, including studies quantifying changes in the
      marrow vascular by microvascular density, do not differentiate between different
      types of marrow vessels. Recognizing changes in different types of blood vessels
      after chemotherapy exposure or during leukemia development has important
      physiological implications. We hypothesized that the functional heterogeneity of
      marrow vasculature could be recognized through the use of functional markers such
      as tyrosine kinase with immunoglobulin and epidermal growth factor homology
      domains-2 (Tie2) expression or 1,1-dioctadecyl -3,3,3,3-tetramethyl
      indocarbocyanine perchlorate with acetylated low-density lipoprotein (DiI-Ac-LDL)
      uptake. METHODS AND RESULTS: When transgenic mice with green fluorescent protein
      (GFP) expressed downstream of the Tie2 promoter were injected with Ac-LDL, Ac-LDL
      was specifically endocytosed by sinusoids, and Tie2 expression was more
      pronounced in the arteries, arterioles, and transitional capillaries. Combining
      these 2 functional endothelial markers and using confocal microscopy to obtain 3
      dimensional images, we identified transitional zones where arterioles emptied
      into the sinusoids. Alternatively, coinjection of lectin with DiI-Ac-LDL has a
      similar result in normal mice, as seen in Tie2/GFP mice, and can be used to
      differentiate vessel types in nontransgenic mice. CONCLUSIONS: These results
      demonstrate that bone marrow vasculature is functionally heterogeneous. Methods
      to study changes in the marrow vasculature using microvascular density or
      quantifying changes in the vascular niche need to take this heterogeneity into
      account.

PMID- 19858417
TI  - Anthropometry, body fat, and venous thromboembolism: a Danish follow-up study.
AB  - BACKGROUND: Obesity, measured as body mass index, is associated with venous
      thromboembolism (VTE). Body mass index is a marker of excess weight and
      correlates well with body fat content in adults; however, it fails to consider
      the distribution of body fat. We assessed the association between anthropometric
      variables and VTE. METHODS AND RESULTS: From 1993 to 1997, 27 178 men and 29 876
      women 50 to 64 years of age were recruited into a Danish prospective study (Diet,
      Cancer, and Health). During 10 years of follow-up, the outcome of VTE events was
      identified in the Danish National Patient Registry and verified by review of
      medical records. Body weight, body mass index, waist circumference, hip
      circumference, and total body fat were measured at baseline. We used Cox
      proportional hazard models to assess the association between anthropometry and
      VTE. Age was used as a time axis, with further adjustment for smoking, physical
      activity, height, hypertension, diabetes mellitus, cholesterol, and, among women,
      use of hormone replacement therapy. We verified 641 incident VTE events and found
      monotonic dose-response relationships between VTE and all anthropometric
      measurements in both sexes. In mutually adjusted analyses of waist and hip
      circumference, we found that hip circumference was positively associated with VTE
      in women but not in men, whereas waist circumference was positively associated
      with VTE in men but not in women. CONCLUSIONS: All measurements of obesity are
      predictors of the risk for VTE. Positive associations were found between VTE and
      body weight, body mass index, waist circumference, hip circumference, and total
      body fat mass.

PMID- 19858416
TI  - Hyperhomocysteinemia promotes inflammatory monocyte generation and accelerates
      atherosclerosis in transgenic cystathionine beta-synthase-deficient mice.
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for
      cardiovascular disease. Monocytes display inflammatory and resident subsets and
      commit to specific functions in atherogenesis. In this study, we examined the
      hypothesis that HHcy modulates monocyte heterogeneity and leads to
      atherosclerosis. METHODS AND RESULTS: We established a novel atherosclerosis
      susceptible mouse model with both severe HHcy and hypercholesterolemia in which
      the mouse cystathionine beta-synthase (CBS) and apolipoprotein E (apoE) genes are
      deficient and an inducible human CBS transgene is introduced to circumvent the
      neonatal lethality of the CBS deficiency (Tg-hCBS apoE(-/-) Cbs(-/-) mice).
      Severe HHcy accelerated atherosclerosis and inflammatory monocyte/macrophage
      accumulation in lesions and increased plasma tumor necrosis factor-alpha and
      monocyte chemoattractant protein-1 levels in Tg-hCBS apoE(-/-) Cbs(-/-) mice fed
      a high-fat diet. Furthermore, we characterized monocyte heterogeneity in Tg-hCBS
      apoE(-/-) Cbs(-/-) mice and another severe HHcy mouse model (Tg-S466L Cbs(-/-))
      with a disease-relevant mutation (Tg-S466L) that lacks hyperlipidemia. HHcy
      increased monocyte population and selective expansion of inflammatory Ly-6C(hi)
      and Ly-6C(mid) monocyte subsets in blood, spleen, and bone marrow of Tg-S466L
      Cbs(-/-) and Tg-hCBS apoE(-/-) Cbs(-/-) mice. These changes were exacerbated in
      Tg-S466L Cbs(-/-) mice with aging. Addition of l-homocysteine (100 to 500
      micromol/L), but not l-cysteine, maintained the Ly-6C(hi) subset and induced the
      Ly-6C(mid) subset in cultured mouse primary splenocytes. Homocysteine-induced
      differentiation of the Ly-6C(mid) subset was prevented by catalase plus
      superoxide dismutase and the NAD(P)H oxidase inhibitor apocynin. CONCLUSIONS:
      HHcy promotes differentiation of inflammatory monocyte subsets and their
      accumulation in atherosclerotic lesions via NAD(P)H oxidase-mediated oxidant
      stress.

PMID- 19858418
TI  - Glycome and transcriptome regulation of vasculogenesis.
AB  - BACKGROUND: Therapeutic vasculogenesis is an emerging concept that can
      potentially be harnessed for the management of ischemic pathologies. The present
      study elucidates the potential coregulation of vasculogenesis by the heparan
      sulfate glycosaminoglycan-rich cell-surface glycome and the transcriptome.
      METHODS AND RESULTS: Differentiation of embryonic stem cells into endothelial
      cells in an in vitro embryoid body is paralleled by an amplification of heparan
      sulfate glycosaminoglycan sulfation, which correlates with the levels of the
      enzyme N-deacetylase/N-sulfotransferase 1 (NDST1). Small hairpin RNA-mediated
      knockdown of NDST1 or modification of heparan sulfate glycosaminoglycans in
      embryonic stem cells with heparinases or sodium chlorate inhibited
      differentiation of embryonic stem cells into endothelial cells. This was
      translated to an in vivo zebrafish embryo model, in which the genetic knockdown
      of NDST1 resulted in impaired vascularization characterized by a concentration
      dependent decrease in intersegmental vessel lumen and a large tail-vessel
      configuration, which could be rescued by use of exogenous sulfated heparan
      sulfate glycosaminoglycans. To explore the cross talk between the glycome and the
      transcriptome during vasculogenesis, we identified by microarray and then
      validated wild-type and NDST1 knockdown-associated gene-expression patterns in
      zebrafish embryos. Temporal analysis at 3 developmental stages critical for
      vasculogenesis revealed a cascade of pathways that may mediate glycocalyx
      regulation of vasculogenesis. These pathways were intimately connected to cell
      signaling, cell survival, and cell fate determination. Specifically, we
      demonstrated that forkhead box O3A/5 proteins and insulin-like growth factor were
      key downstream signals in this process. CONCLUSIONS: The present study for the
      first time implicates interplay between the glycome and the transcriptome during
      vasculogenesis, revealing the possibility of harnessing specific cellular glyco
      microenvironments for therapeutic vascularization.

PMID- 19858420
TI  - Images in cardiovascular medicine. Functional cardiac phenotypes in zebrafish
      caldesmon morphants: a digital motion analysis.

PMID- 19858419
TI  - Cardiac resynchronization induces major structural and functional reverse
      remodeling in patients with New York Heart Association class I/II heart failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves LV structure,
      function, and clinical outcomes in New York Heart Association class III/IV heart
      failure with prolonged QRS. It is not known whether patients with New York Heart
      Association class I/II systolic heart failure exhibit left ventricular (LV)
      reverse remodeling with CRT or whether reverse remodeling is modified by the
      cause of heart failure. METHODS AND RESULTS: Six hundred ten patients with New
      York Heart Association class I/II heart failure, QRS duration > or =120 ms, LV
      end-diastolic dimension > or =55 mm, and LV ejection fraction < or =40% were
      randomized to active therapy (CRT on; n=419) or control (CRT off; n=191) for 12
      months. Doppler echocardiograms were recorded at baseline, before hospital
      discharge, and at 6 and 12 months. When CRT was turned on initially, immediate
      changes occurred in LV volumes and ejection fraction; however, these changes did
      not correlate with the long-term changes (12 months) in LV end-systolic (r=0.11,
      P=0.31) or end-diastolic (r=0.10, P=0.38) volume indexes or LV ejection fraction
      (r=0.07, P=0.72). LV end-diastolic and end-systolic volume indexes decreased in
      patients with CRT turned on (both P<0.001 compared with CRT off), whereas LV
      ejection fraction in CRT-on patients increased (P<0.0001 compared with CRT off)
      from baseline through 12 months. LV mass, mitral regurgitation, and LV diastolic
      function did not change in either group by 12 months; however, there was a 3-fold
      greater reduction in LV end-diastolic and end-systolic volume indexes and a 3
      fold greater increase in LV ejection fraction in patients with nonischemic causes
      of heart failure. CONCLUSIONS: CRT in patients with New York Heart Association
      I/II resulted in major structural and functional reverse remodeling at 1 year,
      with the greatest changes occurring in patients with a nonischemic cause of heart
      failure. CRT may interrupt the natural disease progression in these patients.
      Clinical Trial Registration- Clinicaltrials.gov Identifier: NCT00271154.

PMID- 19858421
TI  - Letter by Choi et al regarding article, "Effects of the selective estrogen
      receptor modulator raloxifene on coronary outcomes in the raloxifene use for the
      heart trial: results of subgroup analyses by age and other factors".

PMID- 19858422
TI  - Letter by Ala-Korpela et al regarding article, "Lipoprotein particle profiles by
      nuclear magnetic resonance compared with standard lipids and apolipoproteins in
      predicting incident cardiovascular disease in women".

PMID- 19858425
TI  - Images in cardiovascular medicine. Pectus excavatum with compression of the
      inferior vena cava: a rare cause of recurrent syncope.

PMID- 19858424
TI  - Time is of the essence: vascular implications of the circadian clock.

PMID- 19858426
TI  - Re: Anti-angiogenic therapy using thalidomide combined with chemotherapy in small
      cell lung cancer: a randomized, double-blind, placebo-controlled trial.

PMID- 19858427
TI  - Adverse events in randomized trials: neglected, restricted, distorted, and
      silenced.

PMID- 19858428
TI  - Women's cardiovascular health: prevention is key.

PMID- 19858429
TI  - Nondaily and social smoking: an increasingly prevalent pattern.

PMID- 19858430
TI  - Going off-label without venturing off-course: evidence and ethical off-label
      prescribing.

PMID- 19858431
TI  - The potency of team-based care interventions for hypertension: a meta-analysis.
AB  - BACKGROUND: Team-based care is the strategy that has had the greatest effect on
      improving blood pressure (BP). The purpose of this systematic review was to
      determine the potency of interventions for BP involving nurses or pharmacists.
      METHODS: A MEDLINE search for controlled clinical trials that involved a nurse or
      pharmacist intervention was conducted. Mean reductions in systolic (S) and
      diastolic (D) BP were determined by 2 reviewers who independently abstracted data
      and classified the different intervention components. RESULTS: Thirty-seven
      articles met the inclusion criteria. Education about BP medications was
      significantly associated with a reduction in mean BP (-8.75/-3.60 mm Hg). Other
      strategies that had large effect sizes on SBP include pharmacist treatment
      recommendations (-9.30 mm Hg), intervention by nurses (-4.80 mm Hg), and use of a
      treatment algorithm (-4.00 mm Hg). The odds ratios (95% confidence intervals) for
      controlled BP were: nurses, 1.69 (1.48-1.93); pharmacists within primary care
      clinics, 2.17 (1.75-2.68); and community pharmacists, 2.89 (1.83-4.55). Mean (SD)
      reductions in SBP were: nursing studies, 5.84 (8.05) mm Hg; pharmacists in
      clinics, 7.76 (7.81) mm Hg; and community pharmacists, 9.31 (5.00) mm Hg. There
      were no significant differences between the nursing and pharmacy studies (P > or
      = .19). CONCLUSIONS: Team-based care was associated with improved BP control, and
      individual components of the intervention appeared to predict potency.
      Implementation of new hypertension guidelines should consider changes in health
      care organizational structure to include important components of team-based care.

PMID- 19858432
TI  - Reporting of safety results in published reports of randomized controlled trials.
AB  - BACKGROUND: Reports of clinical trials usually emphasize efficacy results,
      especially when results are statistically significant. Poor safety reporting can
      lead to misinterpretation and inadequate conclusions about the interventions
      assessed. Our aim was to describe the reporting of harm-related results from
      randomized controlled trials (RCTs). METHODS: We searched the MEDLINE database
      for reports of RCTs published from January 1, 2006, through January 1, 2007, in 6
      general medical journals with a high impact factor. Data were extracted by use of
      a standardized form to appraise the presentation of safety results in text and
      tables. RESULTS: Adverse events were mentioned in 88.7% of the 133 reports. No
      information on severe adverse events and withdrawal of patients owing to an
      adverse event was given in 27.1% and 47.4% of articles, respectively.
      Restrictions in the reporting of harm-related data were noted in 43 articles
      (32.3%) with a description of the most common adverse events only (n = 17),
      severe adverse events only (n = 16), statistically significant events only (n =
      5), and a combination of restrictions (n = 5). The population considered for
      safety analysis was clearly reported in 65.6% of articles. CONCLUSION: Our review
      reveals important heterogeneity and variability in the reporting of harm-related
      results in publications of RCTs.

PMID- 19858433
TI  - Sex-specific trends in midlife coronary heart disease risk and prevalence.
AB  - BACKGROUND: While recent data indicate that stroke prevalence in women at midlife
      is double that of similarly aged men in the United States, little is known about
      current sex-specific trends in symptomatic cardiovascular disease. This study
      aimed to determine sex-specific midlife prevalence of myocardial infarction (MI)
      and risk of future coronary heart disease. METHODS: We assessed the sex-specific
      MI prevalence and the Framingham coronary risk score (FCRS) among US adults aged
      35 to 54 years who participated in the National Health and Nutrition Examination
      Surveys (NHANES), cross-sectional, nationally representative surveys, during 1988
      to 1994 and 1999 to 2004. RESULTS: In both epochs, men aged 35 to 54 years had a
      higher prevalence of MI than similarly aged women, but the gap narrowed in recent
      years as MI prevalence decreased among men and increased among women (2.5% vs
      0.7% in NHANES 1988-1994 [P < .01] and 2.2% vs 1.0% in NHANES 1999-2004 [P <
      .01]). Among men, the mean FCRS showed an improving trend (8.6% in NHANES 1988
      1994 vs 8.1% in NHANES 1999-2004 [P = .07]), while among women, the mean FCRS
      worsened (3.0% in NHANES 1988-1994 vs 3.3% in NHANES 1999-2004 [P = .02]).
      Temporal trends in FCRS components revealed that men had more improvements in
      vascular risk factors than women, but diabetes mellitus prevalence increased in
      both sexes. CONCLUSIONS: Over the past 2 decades, MI prevalence has increased
      among midlife women, while declining among similarly aged men. Also, although the
      risk of future hard cardiovascular events remains higher in midlife men compared
      with midlife women, the gap has narrowed in recent years. Greater emphasis on
      vascular risk factor control in midlife women might help mitigate this worrisome
      trend.

PMID- 19858434
TI  - Sex differences in mortality after acute myocardial infarction: changes from 1994
      to 2006.
AB  - BACKGROUND: Previous studies have shown that women younger than 55 years have
      higher hospital mortality rates after acute myocardial infarction (MI) than age
      matched men. We examined whether such mortality differences have decreased in
      recent years. METHODS: We investigated temporal trends in the hospital case
      fatality rates of MI by sex and age from June 1, 1994, through December 31, 2006.
      The study population included 916,380 patients from the National Registry of
      Myocardial Infarction with a confirmed diagnosis of MI. RESULTS: In-hospital
      mortality decreased markedly between 1994 and 2006 in all patients but more so in
      women than men. The mortality reduction in 2006 relative to 1994 was largest in
      women younger than 55 years (52.9%) and lowest in men younger than 55 years
      (33.3%). In patients younger than 55 years, the absolute decrease in mortality
      was 3 times larger in women than men (2.7% vs 0.9%). As a result, the excess
      mortality in younger women (<55 years) compared with men was less pronounced in
      2004-2006 (unadjusted odds ratio, 1.32; 95% confidence interval, 1.07-1.67) than
      it was in 1994-1995 (unadjusted odds ratio, 1.93; 95% confidence interval, 1.67
      2.24). The sex difference in mortality decrease was lower in older patients (P =
      .004 for the interaction among sex, age, and year). Changes in comorbidity and
      clinical severity features at admission accounted for more than 90% of these
      mortality trends. CONCLUSIONS: In recent years, women, particularly younger ones,
      experienced larger improvements in hospital mortality after MI than men. The
      narrowing of the mortality gap between younger women and men is largely
      attributable to temporal changes in risk profiles.

PMID- 19858435
TI  - Evaluating the incremental benefits of raising high-density lipoprotein
      cholesterol levels during lipid therapy after adjustment for the reductions in
      other blood lipid levels.
AB  - BACKGROUND: The role of high-density lipoprotein cholesterol (HDL-C) as a
      therapeutic target to prevent cardiovascular (CV) events remains unclear. We
      examined data from the Framingham Offspring Study from 1975 through 2003 to
      determine whether increases in HDL-C levels after lipid therapy was started were
      independently associated with a reduction in CV events. METHODS: Using Cox
      proportional-hazards regression, we evaluated the risk of a CV event associated
      with changes in blood lipid levels among individuals who started lipid therapy.
      The independent effect of HDL-C levels on future CV risk (average follow-up, 8
      years) was estimated after adjustment for changes in low-density lipoprotein
      cholesterol, plasma triglycerides, and pretreatment blood lipid levels. Potential
      confounders (eg, smoking status, weight, and the use of beta-blockers) were then
      added to the model. Interactions between blood lipid levels were also explored.
      RESULTS: The change in HDL-C level was a strong independent risk factor for CV
      events (hazard ratio, 0.79 per 5-mg/dL increase; 95% confidence interval, 0.67
      0.93) after adjustment for the other lipid changes associated with treatment.
      This relationship remained stable across a wide range of patient subgroups and
      did not appear to be associated with a specific drug class. An important
      interaction was observed: the lower the pretreatment low-density lipoprotein
      cholesterol level, the greater the impact of raising the HDL-C. CONCLUSIONS:
      Raising HDL-C levels with commonly used lipid medications appears to be an
      important determinant of the benefits associated with lipid therapy. These
      results support the further evaluation of therapies to raise HDL-C levels to
      prevent CV events.

PMID- 19858436
TI  - Role of lifestyle and aging on the longitudinal change in cardiorespiratory
      fitness.
AB  - BACKGROUND: Cardiorespiratory fitness (CRF) in adults decreases with age and is
      influenced by lifestyle. Low CRF is associated with risk of diseases and the
      ability of older persons to function independently. We defined the longitudinal
      rate of CRF decline with aging and the association of aging and lifestyle with
      CRF. METHODS: We studied a cohort of 3429 women and 16 889 men, aged 20 to 96
      years, from the Aerobics Center Longitudinal Study who completed 2 to 33 health
      examinations from 1974 to 2006. The lifestyle variables were body mass index,
      self-reported aerobic exercise, and smoking behavior. Cardiorespiratory fitness
      was measured by a maximal Balke treadmill exercise test. RESULTS: Linear mixed
      models regression analysis stratified by sex showed that the decline in CRF with
      age was not linear. After 45 years of age, CRF declined at an accelerated rate.
      For each unit of increase in body mass index, the CRF of women declined 0.20
      metabolic equivalents (METs) (95% confidence interval, -0.21 to -0.19); that of
      men, 0.32 METs (-0.33 to -0.20). Current smokers of both sexes also had lower CRF
      (-0.29 METs [95% confidence interval, -0.40 to -0.19] for women and -0.41 METS [
      0.44 to -0.38] for men). Cardiorespiratory fitness was positively associated with
      self-reported physical activity. CONCLUSIONS: Cardiorespiratory fitness in men
      and women declines at a nonlinear rate that accelerates after 45 years of age.
      Maintaining a low BMI, being physically active, and not smoking are associated
      with higher CRF across the adult life span.

PMID- 19858437
TI  - The effects of a nurse case manager and a community health worker team on
      diabetic control, emergency department visits, and hospitalizations among urban
      African Americans with type 2 diabetes mellitus: a randomized controlled trial.
AB  - BACKGROUND: Although African American adults bear a disproportionate burden from
      diabetes mellitus (DM), few randomized controlled trials have tested culturally
      appropriate interventions to improve DM care. METHODS: We randomly assigned 542
      African Americans with type 2 DM enrolled in an urban managed care organization
      to either an intensive or minimal intervention group. The intensive intervention
      group consisted of all components of the minimal intervention plus
      individualized, culturally tailored care provided by a nurse case manager (NCM)
      and a community health worker (CHW), using evidence-based clinical algorithms
      with feedback to primary care providers (eg, physicians, nurse practitioners, or
      physician assistants). The minimal intervention consisted of mailings and
      telephone calls every 6 months to remind participants about preventive
      screenings. Data on diabetic control were collected at baseline and at 24 months
      by blind observers; data emergency department (ER) visits and hospitalizations
      were assessed using administrative data. RESULTS: At baseline, participants had a
      mean age of 58 years, 73% were women, and 50% were living in poverty. At 24
      months, compared with the minimal intervention group, those in the intensive
      intervention group were 23% less likely to have ER visits (rate difference [RD], 
      14.5; adjusted rate ratio [RR], 0.77; 95% confidence interval [CI], 0.59-1.00).
      In on-treatment analyses, the rate reduction was strongest for patients who
      received the most NCM and CHW visits (RD, -31.0; adjusted RR, 0.66; 95% CI, 0.43
      1.00; rate reduction downward arrow 34%). CONCLUSION: These data suggest that a
      culturally tailored intervention conducted by an NCM/CHW team reduced ER visits
      in urban African Americans with type 2 DM. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00022750.

PMID- 19858438
TI  - Trial of family and friend support for weight loss in African American adults.
AB  - BACKGROUND: Family and friend participation may provide culturally salient social
      support for weight loss in African American adults. METHODS: SHARE (Supporting
      Healthy Activity and eating Right Everyday) was a 2-year trial of a culturally
      specific weight loss program. African American women and men who enrolled alone
      (individual stratum, 63 index participants) or together with 1 or 2 family
      members or friends (family stratum, 130 index participants) were randomized,
      within strata, to high or low social support treatments; 90% were female.
      RESULTS: At 6 months, the family index participants lost approximately 5 to 6 kg;
      the individual index participants lost approximately 3 to 4 kg. The mean weight
      change was not different in high vs low social support in either stratum and
      generally not when high or low support treatments were compared across strata.
      The overall intention-to-treat mean weight change at 24 months was -2.4 kg (95%
      confidence interval, -3.3 kg to -1.5 kg). The family index participant weight
      loss was greater among the participants whose partners attended more personally
      tailored counseling sessions at 6 months in the high-support group and at 6, 12,
      and 24 months in the low-support group (all P < .05). Also, in the 6-month
      intention-to-treat analysis, the percentage of weight loss of the family index
      participants was greater if partners lost at least 5% vs less than 5% of their
      baseline weight (respectively, -6.1% vs -2.9% [P = .004], high support; and -6.1%
      vs -3.1% [P = .01], low support). CONCLUSIONS: Being assigned to participate with
      family members, friends, or other group members had no effect on weight change.
      Enrolling with others was associated with greater weight loss only when partners
      participated more and lost more weight. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00146081.

PMID- 19858439
TI  - The interdisciplinary approach to culturally tailored medical care: "Social
      networking" for decreasing risk: Comment on "The effects of a nurse case manager
      and a community health worker team on diabetic control, emergency department
      visits, and hospitalizations among urban African Americans with type 2 diabetes
      mellitus: a randomized controlled trial" and "Trial of family and friend support
      for weight loss in African American adults".

PMID- 19858440
TI  - Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6
      years.

PMID- 19858441
TI  - Physicians' experience and satisfaction with chaplains: a national survey.

PMID- 19858442
TI  - ALLHAT findings revisited in the context of subsequent analyses, other trials,
      and meta-analyses.

PMID- 19858443
TI  - Medical oncologists' experience in attending a funeral and communicating
      condolences.

PMID- 19858444
TI  - Acupuncture research: placebos by many other names.

PMID- 19858445
TI  - What is acupuncture after all?

PMID- 19858446
TI  - Concerns about a meta-analysis of computer smoking cessation programs.

PMID- 19858447
TI  - EMRs do not improve reporting rates of abnormal laboratory results?

PMID- 19858448
TI  - Informatics aids to reduce failure rates in notification of abnormal outpatient
      test results.

PMID- 19858449
TI  - Giving patients their results online might be the answer.

PMID- 19858450
TI  - When history really is not applicable or relevant.

PMID- 19858451
TI  - The 300-year-old health care solution.

PMID- 19858452
TI  - Teaching NeuroImages: Primary diffuse large B-cell lymphoma of the cranial vault.

PMID- 19858453
TI  - Teaching NeuroImages: amnesia due to fornix infarction.

PMID- 19858454
TI  - Patient page. Deep brain stimulation for Tourette syndrome.

PMID- 19858456
TI  - CSF biomarkers predict rate of cognitive decline in Alzheimer disease.
AB  - OBJECTIVE: CSF biomarkers amyloid beta 1-42 (Abeta(42)), total tau (tau), and tau
      phosphorylated at threonine 181 (p-tau-181) are useful diagnostic markers for
      Alzheimer disease (AD). Less is known about these biomarkers as predictors for
      further cognitive decline in patients with AD. We hypothesized that high tau,
      especially in combination with relatively low p-tau-181, is a marker of rapid
      decline, since it has been associated with fast neuronal degeneration. METHODS: A
      total of 151 patients with AD of whom we had baseline CSF were included from our
      memory clinic. All patients had at least 2 Mini-Mental State Examination (MMSE)
      scores, obtained no less than 1 year apart. Linear mixed models were used to
      assess associations between CSF biomarkers and the rate of cognitive decline as
      measured with the MMSE. CSF biomarkers were used in quintiles, random intercept
      and random slope with time were assumed, and the analyses were corrected for sex
      and age. RESULTS: The patients with AD (45% women, age 66 +/- 9 years, baseline
      MMSE 22 +/- 4) had a follow-up period of 2.0 (1.0-5.0) years. Linear mixed models
      revealed no relations between any CSF biomarker and baseline MMSE. However, CSF
      biomarkers did predict cognitive decline over time. A low p-tau-181/tau ratio was
      the strongest predictor with a dose-dependent effect (lowest vs highest quintile:
      2.9 vs 1.3 MMSE points annual decline, p for trend <0.001). In addition, low
      Abeta(42), high tau, and high tau/Abeta(42)-ratio were associated with rapid
      cognitive decline (p < 0.05). CONCLUSION: At the time of diagnosis, a combination
      of high CSF tau without proportionally elevated p-tau-181 is associated with a
      faster rate of cognitive decline.

PMID- 19858457
TI  - Diabetes is associated with a slower rate of cognitive decline in Alzheimer
      disease.
AB  - BACKGROUND: Previous epidemiologic studies indicate that diabetes mellitus (DM)
      is associated with cognitive decline and an increased risk of developing
      Alzheimer disease (AD) in people who do not have dementia. However, little is
      known about the effect of DM on the rate of cognitive decline in established AD.
      Our objective was to determine whether DM influences the rate of cognitive
      decline in patients with AD. METHODS: A total of 608 patients with a probable
      diagnosis of AD and a Mini-Mental State Examination (MMSE) score between 10 and
      26 were enrolled in a prospective multicenter study. Participants were followed
      up to 52 (mean 26) months. DM was assessed at baseline (history of DM or
      antidiabetic medication use). Cognitive function was assessed twice yearly with
      the MMSE. RESULTS: Sixty-three participants (10.4%) had DM at baseline. In a
      mixed model adjusted for sex, age, educational level, dementia severity,
      cholinesterase inhibitor use, and vascular factors (hypertension, atrial
      fibrillation, coronary heart disease, and hypercholesterolemia), there were no
      differences between the groups in MMSE baseline scores (-0.75, p = 0.20), but
      cognitive decline was slower in the group with DM (0.38, p = 0.01). CONCLUSIONS:
      In a cohort of community-dwelling patients with Alzheimer disease (AD), the
      presence of diabetes mellitus (DM) was associated with a lower rate of cognitive
      decline. Future studies will need to address the potential impact of DM in the
      cerebral aging process and to assess the neuropathologic variations in patients
      with AD with DM.

PMID- 19858458
TI  - "Frontotemporoparietal" dementia: clinical phenotype associated with the c.709
      1G>A PGRN mutation.
AB  - BACKGROUND: Mutations in the progranulin gene (PGRN) are a major cause of
      frontotemporal lobar degeneration with tau-negative and ubiquitin-positive
      neuronal inclusions. Most previous studies aimed at characterizing the clinical
      and neuropsychological phenotype of PGRN mutation carriers included patients with
      different PGRN mutations, assuming that the common proposed pathogenetic
      mechanism of haploinsufficiency will lead to a comparable phenotype. METHODS: We
      studied 21 patients with a single pathogenic splicing mutation in the PGRN gene
      (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic
      criteria and protocols. All patients were of Basque descent. RESULTS: Patients
      exhibited a variable phenotype both in age at onset and initial symptoms.
      Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent
      aphasia (23.8%) were the most common presenting syndromes. Apathy was the most
      common behavioral symptom. Patients developed a relatively rapidly progressive
      dementia with features that led to a secondary diagnosis in 61.9% of cases 2
      years after primary diagnosis. Notably, this secondary or tertiary diagnosis was
      corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological
      features of parietal lobe dysfunction seen at the initial assessment in 81.8% of
      patients. CONCLUSIONS: Patients carrying the c.709-1G>A mutation in the PGRN gene
      showed heterogeneous clinical and neuropsychological features and commonly
      developed corticobasal syndrome as the disease progressed.

PMID- 19858459
TI  - Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two
      year outcome.
AB  - BACKGROUND: Eighteen patients with severe and refractory Tourette syndrome (TS)
      underwent bilateral thalamic deep brain stimulation (DBS). OBJECTIVE: To assess
      the long-term outcome on tics, behavioral symptoms, and cognitive functions in
      the largest case series of thalamic DBS for TS to date. METHODS: In this
      prospective cohort study, 15 of the original 18 patients were evaluated before
      and after surgery according to a standardized protocol that included both
      neuropsychiatric and neuropsychological assessments. RESULTS: In addition to
      marked reduction in tic severity (p = 0.001), 24-month follow-up ratings showed
      improvement in obsessive-compulsive symptoms (p = 0.009), anxiety symptoms (p =
      0.001), depressive symptoms (p = 0.001), and subjective perception of social
      functioning/quality of life (p = 0.002) in 15 of 18 patients. There were no
      substantial differences on measures of cognitive functions before and after DBS.
      CONCLUSIONS: At 24-month follow-up, tic severity was improved in patients with
      intractable Tourette syndrome (TS) who underwent bilateral thalamic deep brain
      stimulation. Available data from 15 of 18 patients also showed that
      neuropsychiatric symptoms were improved and cognitive performances were not
      disadvantaged. Controlled studies on larger cohorts with blinded protocols are
      needed to verify that this procedure is effective and safe for selected patients
      with TS. LEVEL OF EVIDENCE: This study provides class IV evidence that bilateral
      thalamic deep brain stimulation reduces global tic severity measured 24 months
      after implantation in patients with severe intractable Tourette syndrome.

PMID- 19858461
TI  - Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral
      contraceptives.
AB  - OBJECTIVE: We prospectively evaluated the fluctuation of lamotrigine (LTG)
      clearance during the menstrual cycle. We also assessed the effect of
      postmenopausal status and investigated in detail the effect of oral
      contraceptives (OCs) on LTG clearance. METHODS: Three groups of women with
      epilepsy using LTG monotherapy were evaluated. Women in the first group (n = 7)
      had a regular cycle and did not use OCs; the second group used a 1-phase combined
      OC (n = 7), and the third group (n = 7) was postmenopausal. Two menstrual cycles
      or at least 2 months (postmenopausal women) were assessed, monitoring LTG levels
      every other day. RESULTS: The mean apparent LTG clearance in women of
      reproductive age not using OCs was 49 (SD 22.6, range 20.4-83.5) L/24 hours. No
      significant effect of endogenous hormones on LTG clearance was found. In women
      using OCs, the mean LTG clearance was 126 (SD 60.2, range 44.3-205) L/24 hours.
      There was an increase in LTG levels during the pill-free week, with maximum
      levels 54% (range 29%-129%) higher than baseline levels. LTG levels decreased to
      the baseline value within a mean of 8 days of starting OC use (SD 3.7, range 2.5
      16.5). In the postmenopausal women, the mean clearance was 82 (SD 38.4, range
      35.9-125) L/24 hours. CONCLUSIONS: We observed a higher mean lamotrigine (LTG)
      clearance in postmenopausal women compared with young women not using oral
      contraceptives (OCs) and confirmed that OC use may have a strong effect on LTG
      clearance. There was no significant fluctuation of LTG clearance during the
      menstrual cycle.

PMID- 19858460
TI  - Anemia or low hemoglobin levels preceding Parkinson disease: a case-control
      study.
AB  - OBJECTIVE: It has been suggested that anemia may be a risk factor for dementia,
      for restless legs syndrome, and for Parkinson disease (PD). Thus, we investigated
      the association of anemia with the subsequent risk of PD using a case-control
      study design. METHODS: We used the medical records-linkage system of the
      Rochester Epidemiology Project to identify 196 subjects who developed PD in
      Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched
      by age (+/-1 year) and sex to a general population control. We reviewed the
      complete medical records of cases and controls in the system to detect anemia
      defined using the World Health Organization criteria. RESULTS: Anemia was more
      common in the history of cases than of controls (odds ratio 2.00, 95% confidence
      interval 1.31-3.06, p = 0.001). The association remained significant after
      adjustment for cigarette smoking, exposure to pesticides, or hysterectomy (in
      women). The association was not significantly different between men and women, or
      between PD patients with or without rest tremor. Analyses stratified by time of
      onset of anemia showed a greater association for anemia that started 20 to 29
      years before the onset of PD. Hemoglobin levels were slightly but consistently
      lower in cases than in controls across all ages. CONCLUSIONS: Our results support
      an association between anemia experienced early in life and the later development
      of Parkinson disease. The interpretation of this association remains uncertain.

PMID- 19858462
TI  - A cross-sectional study of bone health in multiple sclerosis.
AB  - BACKGROUND: Osteoporosis is an important risk factor for fragility fractures.
      Although osteoporosis is considered common in multiple sclerosis (MS), few
      previous studies focused on fractures in MS. OBJECTIVE: Using the North American
      Research Committee on Multiple Sclerosis (NARCOMS) Registry, we investigated the
      frequency of osteoporosis, fractures, and clinical risk factors for fracture in
      MS. METHODS: In 2007, 9,346 NARCOMS participants reported fractures and clinical
      risk factors for fractures including history of osteoporosis or osteopenia (low
      bone mass), sedentary level of physical activity, falls in the last year, current
      smoking status, family history of osteoporosis, and impaired mobility. RESULTS:
      Among responders, 2,501 (27.2%) reported low bone mass. More than 15% of
      responders reported a history of fracture after age 13 years (n = 1,482). Among
      those reporting fractures, 685 (46.2%) reported multiple fractures, while 522
      (35.2%) reported a wrist fracture, 165 (11.1%) reported a vertebral fracture, and
      100 (7.4%) reported a hip fracture. Excluding age, 1,413 (15.1%) participants had
      1 clinical risk factor for fracture, 2,341 (25.0%) had 2, and 5,393 (57.7%) had 3
      or more. Among participants with a history of fracture, 746 (55%) reported taking
      calcium supplements, 858 (68.8%) reported taking vitamin D supplements or a
      multivitamin with vitamin D, and 334 (22.5%) reported taking a bisphosphonate.
      CONCLUSION: Patients with multiple sclerosis (MS) often have multiple risk
      factors for osteoporotic fractures. Many patients with MS with low bone mass or
      previous fractures are not taking supplemental calcium or vitamin D, suggesting a
      potential area of improvement in care.

PMID- 19858463
TI  - A 74-year-old woman with progressive right-hand tremor and inability to use her
      right side.

PMID- 19858464
TI  - Neurologic dengue manifestations associated with intrathecal specific immune
      response.
AB  - BACKGROUND: Dengue infection is caused by a flavivirus, with 4 virus serotypes
      (types 1 to 4). The serotypes 2 and 3 represent the principal agents related to
      nervous system involvement. Neurologic involvement occurs in 4%-5% of dengue
      infection cases. The major mechanisms of the disease may be related to direct
      viral infection or postinfectious autoimmune process. The detection of
      intrathecal synthesis of specific antibodies has been used to support neurologic
      diagnosis as a proof of local reaction. It may be quantitatively calculated by
      the specific antibody index. OBJECTIVES: To determine if patients with neurologic
      manifestations associated with dengue produce specific antibodies in the CNS and
      to determine the antibodies' clinical and pathophysiologic relevance. METHODS:
      CSF and serum were evaluated for dengue immunoglobulin M (IgM) and immunoglobulin
      G (IgG) antibodies by ELISA and for intrathecal synthesis of IgG antibodies to
      the dengue virus. Subjects included 10 patients IgM seropositive for dengue virus
      diagnosed with myelitis, encephalitis, optic neuromyelitis, or Guillain-Barre
      syndrome. RESULTS: All patients had IgG and IgM antibodies to dengue virus in
      their sera; 7 were IgM positive and 9 were IgG positive for dengue virus in CSF.
      Only the 3 patients with myelitis had intrathecal synthesis of specific IgG
      antibodies. CONCLUSIONS: Intrathecal synthesis of antibodies to dengue virus
      occurs in the CNS. It may be used as a marker of myelitis associated with dengue,
      and it seems to be related to the pathogenesis of spinal cord disease due to
      direct viral invasion.

PMID- 19858465
TI  - Development of mesial temporal lobe epilepsy in chorea-acanthocytosis.

PMID- 19858466
TI  - Hemorrhagic Wernicke encephalopathy in a patient with liver transplantation.

PMID- 19858467
TI  - Mutations in GBA are associated with familial Parkinson disease susceptibility
      and age at onset.

PMID- 19858468
TI  - Citation and readership metrics: how does Neurology measure up?

PMID- 19858469
TI  - Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood.

PMID- 19858470
TI  - Classic essential tremor changes following cerebellar hemorrhage.

PMID- 19858471
TI  - Stroke following pulmonary arteriovenous fistula embolization in a patient with
      HHT.

PMID- 19858472
TI  - Basic mechanism for abrupt monsoon transitions.
AB  - Monsoon systems influence the livelihood of hundreds of millions of people.
      During the Holocene and last glacial period, rainfall in India and China has
      undergone strong and abrupt changes. Though details of monsoon circulations are
      complicated, observations reveal a defining moisture-advection feedback that
      dominates the seasonal heat balance and might act as an internal amplifier,
      leading to abrupt changes in response to relatively weak external perturbations.
      Here we present a minimal conceptual model capturing this positive feedback. The
      basic equations, motivated by observed relations, yield a threshold behavior,
      robust with respect to addition of other physical processes. Below this threshold
      in net radiative influx, R(c), no conventional monsoon can develop; above R(c),
      two stable regimes exist. We identify a nondimensional parameter l that defines
      the threshold and makes monsoon systems comparable with respect to the character
      of their abrupt transition. This dynamic similitude may be helpful in
      understanding past and future variations in monsoon circulation. Within the
      restrictions of the model, we compute R(c) for current monsoon systems in India,
      China, the Bay of Bengal, West Africa, North America, and Australia, where
      moisture advection is the main driver of the circulation.

PMID- 19858473
TI  - Indirect costs of a nontarget pathogen mitigate the direct benefits of a virus
      resistant transgene in wild Cucurbita.
AB  - Virus-resistant transgenic squash are grown throughout the United States and much
      of Mexico and it is likely that the virus-resistant transgene (VRT) has been
      introduced to wild populations repeatedly. The evolutionary fate of any
      resistance gene in wild populations and its environmental impacts depend upon
      trade-offs between the costs and benefits of the resistance gene. In a 3-year
      field study using a wild gourd and transgenic and nontransgenic introgressives,
      we measured the effects of the transgene on fitness, on herbivory by cucumber
      beetles, on the incidence of mosaic viruses, and on the incidence of bacterial
      wilt disease (a fatal disease vectored by cucumber beetles). In each year, the
      first incidence of zucchini yellow mosaic virus occurred in mid-July and spread
      rapidly through the susceptible plants. We found that the transgenic plants had
      greater reproduction through both male and female function than the susceptible
      plants, indicating that the VRT has a direct fitness benefit for wild gourds
      under the conditions of our study. Moreover, the VRT had no effect on resistance
      to cucumber beetles or the incidence of wilt disease before the spread of the
      virus. However, as the virus spread through the fields, the cucumber beetles
      became increasingly concentrated upon the healthy (mostly transgenic) plants,
      which increased exposure to and the incidence of wilt disease on the transgenic
      plants. This indirect cost of the VRT (mediated by a nontarget herbivore and
      pathogen) mitigated the overall beneficial effect of the VRT on fitness.

PMID- 19858474
TI  - Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both
      animal and human-infective African trypanosomes.
AB  - Several species of African trypanosomes cause fatal disease in livestock, but
      most cannot infect humans due to innate trypanosome lytic factors (TLFs). Human
      TLFs are pore forming high-density lipoprotein (HDL) particles that contain
      apolipoprotein L-I (apoL-I) the trypanolytic component, and haptoglobin-related
      protein (Hpr), which binds free hemoglobin (Hb) in blood and facilitates the
      uptake of TLF via a trypanosome haptoglobin-hemoglobin receptor. The human
      infective Trypanosoma brucei rhodesiense escapes lysis by TLF by expression of
      serum resistance-associated (SRA) protein, which binds and neutralizes apoL-I.
      Unlike humans, baboons are not susceptible to infection by T. b. rhodesiense due
      to previously unidentified serum factors. Here, we show that baboons have a TLF
      complex that contains orthologs of Hpr and apoL-I and that full-length baboon
      apoL-I confers trypanolytic activity to mice and when expressed together with
      baboon Hpr and human apoA-I, provides protection against both animal infective
      and the human-infective T. brucei rhodesiense in vivo. We further define two
      critical lysines near the C terminus of baboon apoL-1 that are necessary and
      sufficient to prevent binding to SRA and thereby confer resistance to human
      infective trypanosomes. These findings form the basis for the creation of TLF
      transgenic livestock that would be resistant to animal and human-infective
      trypanosomes, which would result in the reduction of disease and the zoonotic
      transmission of human infective trypanosomes.

PMID- 19858475
TI  - Interdependence of movement and anatomy persists when amputees learn a
      physiologically impossible movement of their phantom limb.
AB  - The feeling we have of our own body, sometimes called "body image," is
      fundamental to self-awareness. However, by altering sensory input, the body image
      can be modified into impossible configurations. Can impossible movements of the
      body image be conjured solely via internally generated mechanisms, and, if so, do
      the structural characteristics of the body image modify to accommodate the new
      movements? We encouraged seven amputees with a vivid phantom arm to learn to
      perform a phantom wrist movement that defied normal anatomical constraints. Four
      reported success. Learning the impossible movement coincided in time with a
      profound change in the body image of the arm, including a sense of ownership and
      agency over a modified wrist joint. Remarkably, some previous movements and
      functional tasks involving the phantom arm became more difficult once the shift
      in body image had occurred. Crucially, these introspective reports were
      corroborated by robust empirical data from motor imagery tasks, about which
      amputees were naive and to which assessors were blind. These results provide
      evidence that: a completely novel body image can be constructed solely by
      internally generated mechanisms; that the interdependence between movement
      repertoire and structural constraints of the body persists even when the
      structural constraints imparted by the body do not--the body image we construct
      still constrains imagined movements; and that motor learning does not necessarily
      need sensory feedback from the body or external feedback about task performance.

PMID- 19858476
TI  - Colloquium papers: Natural selection in a contemporary human population.
AB  - Our aims were to demonstrate that natural selection is operating on contemporary
      humans, predict future evolutionary change for specific traits with medical
      significance, and show that for some traits we can make short-term predictions
      about our future evolution. To do so, we measured the strength of selection,
      estimated genetic variation and covariation, and predicted the response to
      selection for women in the Framingham Heart Study, a project of the National
      Heart, Lung, and Blood Institute and Boston University that began in 1948. We
      found that natural selection is acting to cause slow, gradual evolutionary
      change. The descendants of these women are predicted to be on average slightly
      shorter and stouter, to have lower total cholesterol levels and systolic blood
      pressure, to have their first child earlier, and to reach menopause later than
      they would in the absence of evolution. Selection is tending to lengthen the
      reproductive period at both ends. To better understand and predict such changes,
      the design of planned large, long-term, multicohort studies should include input
      from evolutionary biologists.

PMID- 19858477
TI  - Colloquium papers: Numbering the hairs on our heads: the shared challenge and
      promise of phenomics.
AB  - Evolution and medicine share a dependence on the genotype-phenotype map. Although
      genotypes exist and are inherited in a discrete space convenient for many sorts
      of analyses, the causation of key phenomena such as natural selection and disease
      takes place in a continuous phenotype space whose relationship to the genotype
      space is only dimly grasped. Direct study of genotypes with minimal reference to
      phenotypes is clearly insufficient to elucidate these phenomena. Phenomics, the
      comprehensive study of phenotypes, is therefore essential to understanding
      biology. For all of the advances in knowledge that a genomic approach to biology
      has brought, awareness is growing that many phenotypes are highly polygenic and
      susceptible to genetic interactions. Prime examples are common human diseases.
      Phenomic thinking is starting to take hold and yield results that reveal why it
      is so critical. The dimensionality of phenotypic data are often extremely high,
      suggesting that attempts to characterize phenotypes with a few key measurements
      are unlikely to be completely successful. However, once phenotypic data are
      obtained, causation can turn out to be unexpectedly simple. Phenotypic data can
      be informative about the past history of selection and unexpectedly predictive of
      long-term evolution. Comprehensive efforts to increase the throughput and range
      of phenotyping are an urgent priority.

PMID- 19858478
TI  - Cultural evolution and individual development of openness and conservatism.
AB  - We present a model of cultural evolution in which an individual's propensity to
      engage in social learning is affected by social learning itself. We assume that
      individuals observe cultural traits displayed by others and decide whether to
      copy them based on their overall preference for the displayed traits.
      Preferences, too, can be transmitted between individuals. Our results show that
      such cultural dynamics tends to produce conservative individuals, i.e.,
      individuals who are reluctant to copy new traits. Openness to new information,
      however, can be maintained when individuals need significant time to acquire the
      cultural traits that make them effective cultural models. We show that a gradual
      enculturation of young individuals by many models and a larger cultural
      repertoire to be acquired are favorable circumstances for the long-term
      maintenance of openness in individuals and groups. Our results agree with data
      about lifetime personality change, showing that openness to new information
      decreases with age. Our results show that cultural remodeling of cultural
      transmission is a powerful force in cultural evolution, i.e., that cultural
      evolution can change its own dynamics.

PMID- 19858479
TI  - Cloning human herpes virus 6A genome into bacterial artificial chromosomes and
      study of DNA replication intermediates.
AB  - Cloning of large viral genomes into bacterial artificial chromosomes (BACs)
      facilitates analyses of viral functions and molecular mutagenesis. Previous
      derivations of viral BACs involved laborious recombinations within infected
      cells. We describe a single-step production of viral BACs by direct cloning of
      unit length genomes, derived from circular or head-to-tail concatemeric DNA
      replication intermediates. The BAC cloning is independent of intracellular
      recombinations and DNA packaging constraints. We introduced the 160-kb human
      herpes virus 6A (HHV-6A) genome into BACs by digesting the viral DNA replicative
      intermediates with the Sfil enzyme that cleaves the viral genome in a single
      site. The recombinant BACs contained also the puromycin selection gene, GFP, and
      LoxP sites flanking the BAC sequences. The HHV-6A-BAC vectors were retained
      stably in puromycin selected 293T cells. In the presence of irradiated helper
      virus, supplying most likely proteins enhancing gene expression they expressed
      early and late genes in SupT1 T cells. The method is especially attractive for
      viruses that replicate inefficiently and for viruses propagated in suspension
      cells. We have used the fact that the BAC cloning "freezes" the viral DNA
      replication intermediates to analyze their structure. The results revealed that
      HHV-6A-BACs contained a single direct repeat (DR) rather than a DR-DR sequence,
      predicted to arise by circularization of parental genomes with a DR at each
      terminus. HHV-6A DNA molecules prepared from the infected cells also contained
      DNA molecules with a single DR. Such forms were not previously described for HHV
      6 DNA.

PMID- 19858480
TI  - Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced
      aggression in a monogamous rodent.
AB  - After pair-bonding, male prairie voles (Microtus ochrogaster) display aggression
      toward novel females but not toward their female partner. Here we show that this
      selective aggression in pair-bonded male prairie voles is associated with
      increased release of vasopressin (AVP) in the anterior hypothalamus (AH).
      Pharmacological activation of AVP-V1a receptors (V1aR) in the AH induced
      selective aggression in sexually naive males, whereas V1aR blockade diminished
      selective aggression in pair-bonded males. Pair-bonded males also showed an
      increased density in V1aR binding in the AH compared to their sexually naive
      counterparts and overexpression of V1aR in the AH, by viral vector-mediated gene
      transfer, facilitated aggression toward novel females. These data demonstrate
      that AH-AVP is both necessary and sufficient in the regulation of selective
      aggression associated with pair-bonding. In the second part of this study, we
      examined the effects of amphetamine (AMPH) exposure on female-directed aggression
      and revealed the potential role of AH-AVP underlying this behavior. Repeated AMPH
      administration in sexually naive male prairie voles enhanced V1aR expression in
      the AH and induced aggression toward a familiar or unfamiliar female. In
      addition, this AMPH-induced aggression was blocked by intra-AH administration of
      a V1aR antagonist. Together, our data reveal a socioneurobiological mechanism,
      highlighting a critical role of AH-AVP in the regulation of aggression induced by
      pair-bonding or drug experience in socially monogamous male prairie voles.

PMID- 19858481
TI  - A chemical-genetic approach to study G protein regulation of beta cell function
      in vivo.
AB  - Impaired functioning of pancreatic beta cells is a key hallmark of type 2
      diabetes. beta cell function is modulated by the actions of different classes of
      heterotrimeric G proteins. The functional consequences of activating specific
      beta cell G protein signaling pathways in vivo are not well understood at
      present, primarily due to the fact that beta cell G protein-coupled receptors
      (GPCRs) are also expressed by many other tissues. To circumvent these
      difficulties, we developed a chemical-genetic approach that allows for the
      conditional and selective activation of specific beta cell G proteins in intact
      animals. Specifically, we created two lines of transgenic mice each of which
      expressed a specific designer GPCR in beta cells only. Importantly, the two
      designer receptors differed in their G protein-coupling properties (G(q/11)
      versus G(s)). They were unable to bind endogenous ligand(s), but could be
      efficiently activated by an otherwise pharmacologically inert compound (clozapine
      N-oxide), leading to the conditional activation of either beta cell G(q/11) or
      G(s) G proteins. Here we report the findings that conditional and selective
      activation of beta cell G(q/11) signaling in vivo leads to striking increases in
      both first- and second-phase insulin release, greatly improved glucose tolerance
      in obese, insulin-resistant mice, and elevated beta cell mass, associated with
      pathway-specific alterations in islet gene expression levels. Selective
      stimulation of beta cell G(s) triggered qualitatively similar in vivo metabolic
      effects. Thus, this developed chemical-genetic strategy represents a powerful
      approach to study G protein regulation of beta cell function in vivo.

PMID- 19858482
TI  - Evolution in health and medicine Sackler colloquium: The comparative genomics of
      viral emergence.
AB  - RNA viruses are the main agents of emerging and re-emerging diseases. It is
      therefore important to reveal the evolutionary processes that underpin their
      ability to jump species boundaries and establish themselves in new hosts. Here, I
      discuss how comparative genomics can contribute to this endeavor. Arguably the
      most important evolutionary process in RNA virus evolution, abundant mutation,
      may even open up avenues for their control through "lethal mutagenesis." Despite
      this remarkable mutational power, adaptation to diverse host species remains a
      major adaptive challenge, such that the most common outcome of host jumps are
      short-term "spillover" infections. A powerful case study of the utility of
      genomic approaches to studies of viral evolution and emergence is provided by
      influenza virus and brought into sharp focus by the ongoing epidemic of swine
      origin H1N1 influenza A virus (A/H1N1pdm). Research here reveals a marked lack of
      surveillance of influenza viruses in pigs, coupled with the possibility of
      cryptic transmission before the first reported human cases, such that the exact
      genesis of A/H1N1pdm (where, when, how) is uncertain.

PMID- 19858483
TI  - Complex embryos displaying bilaterian characters from Precambrian Doushantuo
      phosphate deposits, Weng'an, Guizhou, China.
AB  - Three-dimensionally preserved embryos from the Precambrian Ediacaran Doushantuo
      Formation, Weng'an, Guizhou, southern China, have attracted great attention as
      the oldest fossil evidence yet found for multicellular animal life on Earth. Many
      embryos are early cleavage embryos and most of them yield a limited phylogenetic
      signal. Here we report the discovery of two Doushantuo embryos that are three
      dimensionally preserved and complex. Imaging techniques using propagation phase
      contrast based synchrotron radiation microtomography (PPC-SR-microCT) reveal that
      the organization of cells demonstrates several bilaterian features, including the
      formation of anterior-posterior, dorso-ventral, and right-left polarities, and
      cell differentiation. Unexpectedly, our observations show a noticeable difference
      in organization patterns between the embryos, suggesting that they represent two
      distinct taxa. These embryos provide further evidence for the presence of
      bilaterian animals in the Doushantuo biota. Furthermore, these bilaterians had
      already diverged into distantly related groups at least 40 million years before
      the Cambrian radiation, indicating that the last common ancestor of the
      bilaterians lived much earlier than is usually thought.

PMID- 19858484
TI  - Migratory double breeding in Neotropical migrant birds.
AB  - Neotropical migratory songbirds typically breed in temperate regions and then
      travel long distances to spend the majority of the annual cycle in tropical
      wintering areas. Using stable-isotope methodology, we provide quantitative
      evidence of dual breeding ranges for 5 species of Neotropical migrants. Each is
      well known to have a Neotropical winter range and a breeding range in the United
      States and Canada. However, after their first bout of breeding in the north, many
      individuals migrate hundreds to thousands of kilometers south in midsummer to
      breed a second time during the same summer in coastal west Mexico or Baja
      California Sur. They then migrate further south to their final wintering areas in
      the Neotropics. Our discovery of dual breeding ranges in Neotropical migrants
      reveals a hitherto unrealized flexibility in life-history strategies for these
      species and underscores that demographic models and conservation plans must
      consider dual breeding for these migrants.

PMID- 19858486
TI  - Global mapping of Al, Cu, Fe, and Zn in-use stocks and in-ground resources.
AB  - Human activity has become a significant geomorphic force in modern times,
      resulting in unprecedented movements of material around Earth. An essential
      constituent of this material movement, the major industrial metals aluminium,
      copper, iron, and zinc in the human-built environment are mapped globally at 1-km
      nominal resolution for the year 2000 and compared with the locations of present
      day in-ground resources. While the maps of in-ground resources generated
      essentially combine available databases, the mapping methodology of in-use stocks
      relies on the linear regression between gross domestic product and both in-use
      stock estimates and the Nighttime Lights of the World dataset. As the first
      global maps of in-use metal stocks, they reveal that a full 25% of the world's
      Fe, Al, Cu, and Zn in-use deposits are concentrated in three bands: (i) the
      Eastern seaboard from Washington, D.C. to Boston in the United States, (ii)
      England, Benelux into Germany and Northern Italy, and (iii) South Korea and
      Japan. This pattern is consistent across all metals investigated. In contrast,
      the global maps of primary metal resources reveal these deposits are more evenly
      distributed between the developed and developing worlds, with the distribution
      pattern differing depending on the metal. This analysis highlights the magnitude
      at which in-ground metal resources have been translocated to in-use stocks,
      largely from highly concentrated but globally dispersed in-ground deposits to
      more diffuse in-use stocks located primarily in developed urban regions.

PMID- 19858485
TI  - Hypersensitivity to contact inhibition provides a clue to cancer resistance of
      naked mole-rat.
AB  - The naked mole-rat is the longest living rodent with a maximum lifespan exceeding
      28 years. In addition to its longevity, naked mole-rats have an extraordinary
      resistance to cancer as tumors have never been observed in these rodents.
      Furthermore, we show that a combination of activated Ras and SV40 LT fails to
      induce robust anchorage-independent growth in naked mole-rat cells, while it
      readily transforms mouse fibroblasts. The mechanisms responsible for the cancer
      resistance of naked mole-rats were unknown. Here we show that naked mole-rat
      fibroblasts display hypersensitivity to contact inhibition, a phenomenon we
      termed "early contact inhibition." Contact inhibition is a key anticancer
      mechanism that arrests cell division when cells reach a high density. In cell
      culture, naked mole-rat fibroblasts arrest at a much lower density than those
      from a mouse. We demonstrate that early contact inhibition requires the activity
      of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb
      attenuates early contact inhibition. Contact inhibition in human and mouse is
      triggered by the induction of p27(Kip1). In contrast, early contact inhibition in
      naked mole-rat is associated with the induction of p16(Ink4a). Furthermore, we
      show that the roles of p16(Ink4a) and p27(Kip1) in the control of contact
      inhibition became temporally separated in this species: the early contact
      inhibition is controlled by p16(Ink4a), and regular contact inhibition is
      controlled by p27(Kip1). We propose that the additional layer of protection
      conferred by two-tiered contact inhibition contributes to the remarkable tumor
      resistance of the naked mole-rat.

PMID- 19858487
TI  - Parameters that influence the prediction of epidemiological benefits of more
      effective tuberculosis vaccines, drugs, and diagnosis.

PMID- 19858488
TI  - LACTB is a filament-forming protein localized in mitochondria.
AB  - LACTB is a mammalian active-site serine protein that has evolved from a bacterial
      penicillin-binding protein. Penicillin-binding proteins are involved in the
      metabolism of peptidoglycan, the major bacterial cell wall constituent, implying
      that LACTB has been endowed with novel biochemical properties during eukaryote
      evolution. Here we demonstrate that LACTB is localized in the mitochondrial
      intermembrane space, where it is polymerized into stable filaments with a length
      extending more than a hundred nanometers. We infer that LACTB, through
      polymerization, promotes intramitochondrial membrane organization and micro
      compartmentalization. These findings have implications for our understanding of
      mitochondrial evolution and function.

PMID- 19858489
TI  - p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal
      transition and cancer stem cell-like gene expression in vivo.
AB  - p21(CIP1/WAF1) is a downstream effector of tumor suppressors and functions as a
      cyclin-dependent kinase inhibitor to block cellular proliferation. Breast tumors
      may derive from self-renewing tumor-initiating cells (BT-ICs), which contribute
      to tumor progression, recurrence, and therapy resistance. The role of p21(CIP1)
      in regulating features of tumor stem cells in vivo is unknown. Herein, deletion
      of p21(CIP1), which enhanced the rate of tumorigenesis induced by mammary
      targeted Ha-Ras or c-Myc, enhanced gene expression profiles and
      immunohistochemical features of epithelial mesenchymal transition (EMT) and
      putative cancer stem cells in vivo. Silencing of p21(CIP1) enhanced, and
      expression of p21(CIP1) repressed, features of EMT in transformed immortal human
      MEC lines. p21(CIP1) attenuated oncogene-induced BT-IC and mammosphere formation.
      Thus, the in vitro cell culture assays reflect the changes observed in vivo in
      transgenic mice. These findings establish a link between the loss of p21(CIP1)
      and the acquisition of breast cancer EMT and stem cell properties in vivo.

PMID- 19858490
TI  - Acute olfactory response of Culex mosquitoes to a human- and bird-derived
      attractant.
AB  - West Nile virus, which is transmitted by Culex mosquitoes while feeding on birds
      and humans, has emerged as the dominant vector borne disease in North America. We
      have identified natural compounds from humans and birds, which are detected with
      extreme sensitivity by olfactory receptor neurons (ORNs) on the antennae of Culex
      pipiens quinquefasciatus (Cx. quinquefasciatus). One of these semiochemicals,
      nonanal, dominates the odorant spectrum of pigeons, chickens, and humans from
      various ethnic backgrounds. We determined the specificity and sensitivity of all
      ORN types housed in different sensilla types on Cx. quinquefasciatus antennae.
      Here, we present a comprehensive map of all antennal ORNs coding natural ligands
      and their dose-response functions. Nonanal is detected by a large array of
      sensilla and is by far the most potent stimulus; thus, supporting the assumption
      that Cx. quinquefasciatus can smell humans and birds. Nonanal and CO(2)
      synergize, thus, leading to significantly higher catches of Culex mosquitoes in
      traps baited with binary than in those with individual lures.

PMID- 19858491
TI  - Sexual dimorphism and directional sexual selection on aposematic signals in a
      poison frog.
AB  - It is commonly assumed that natural selection imposed by predators is the
      prevailing force driving the evolution of aposematic traits. Here, we demonstrate
      that aposematic signals are shaped by sexual selection as well. We evaluated
      sexual selection for coloration brightness in populations of the poison frog
      Oophaga [Dendrobates] pumilio in Panama's Bocas del Toro archipelago. We assessed
      female preferences for brighter males by manipulating the perceived brightness of
      spectrally matched males in two-way choice experiments. We found strong female
      preferences for bright males in two island populations and weaker or ambiguous
      preferences in females from mainland populations. Spectral reflectance
      measurements, coupled with an O. pumilio-specific visual processing model, showed
      that O. pumilio coloration was significantly brighter in island than in mainland
      morphs. In one of the island populations (Isla Solarte), males were significantly
      more brightly colored than females. Taken together, these results provide
      evidence for directional sexual selection on aposematic coloration and document
      sexual dimorphism in vertebrate warning coloration. Although aposematic signals
      have long been upheld as exemplars of natural selection, our results show that
      sexual selection should not be ignored in studies of aposematic evolution.

PMID- 19858492
TI  - A theory for the evolution of other-regard integrating proximate and ultimate
      perspectives.
AB  - Although much previous work describes evolutionary mechanisms that promote or
      stabilize different social behaviors, we still have little understanding of the
      factors that drive animal behavior proximately. Here we present a modeling
      approach to answer this question. Our model rests on motivations to achieve
      objectives as the proximate determinants of behavior. We develop a two-tiered
      framework by first modeling the dynamics of a social interaction at the
      behavioral time scale and then find the evolutionarily stable objectives that
      result from the outcomes these dynamics produce. We use this framework to ask
      whether "other-regarding" motivations, which result from a kind of nonselfish
      objective, can evolve when individuals are engaged in a social interaction that
      entails a conflict between their material payoffs. We find that, at the
      evolutionarily stable state, individuals can be other-regarding in that they are
      motivated to increase their partners' payoff as well as their own. In contrast to
      previous theories, we find that such motivations can evolve because of their
      direct effect on fitness and do not require kin selection or a special group
      structure. We also derive general conditions for the evolutionary stability of
      other-regarding motivations. Our conditions indicate that other-regarding
      motivations are more likely to evolve when social interactions and behavioral
      objectives are both synergistic.

PMID- 19858494
TI  - Household actions can provide a behavioral wedge to rapidly reduce US carbon
      emissions.
AB  - Most climate change policy attention has been addressed to long-term options,
      such as inducing new, low-carbon energy technologies and creating cap-and-trade
      regimes for emissions. We use a behavioral approach to examine the reasonably
      achievable potential for near-term reductions by altered adoption and use of
      available technologies in US homes and nonbusiness travel. We estimate the
      plasticity of 17 household action types in 5 behaviorally distinct categories by
      use of data on the most effective documented interventions that do not involve
      new regulatory measures. These interventions vary by type of action and typically
      combine several policy tools and strong social marketing. National implementation
      could save an estimated 123 million metric tons of carbon per year in year 10,
      which is 20% of household direct emissions or 7.4% of US national emissions, with
      little or no reduction in household well-being. The potential of household action
      deserves increased policy attention. Future analyses of this potential should
      incorporate behavioral as well as economic and engineering elements.

PMID- 19858493
TI  - Nicotine response genetics in the zebrafish.
AB  - Tobacco use is predicted to result in over 1 billion deaths worldwide by the end
      of the 21(st) century. How genetic variation contributes to the observed
      differential predisposition in the human population to drug dependence is
      unknown. The zebrafish (Danio rerio) is an emerging vertebrate model system for
      understanding the genetics of behavior. We developed a nicotine behavioral assay
      in zebrafish and applied it in a forward genetic screen using gene-breaking
      transposon mutagenesis. We used this method to molecularly characterize bdav/cct8
      and hbog/gabbr1.2 as mutations with altered nicotine response. Each have a single
      human ortholog, identifying two points for potential scientific, diagnostic, and
      drug development for nicotine biology and cessation therapeutics. We show this
      insertional method generates mutant alleles that are reversible through Cre
      mediated recombination, representing a conditional mutation system for the
      zebrafish. The combination of this reporter-tagged insertional mutagen approach
      and zebrafish provides a powerful platform for a rich array of questions amenable
      to genetic-based scientific inquiry, including the basis of behavior,
      epigenetics, plasticity, stress, memory, and learning.

PMID- 19858495
TI  - Message-passing algorithms for compressed sensing.
AB  - Compressed sensing aims to undersample certain high-dimensional signals yet
      accurately reconstruct them by exploiting signal characteristics. Accurate
      reconstruction is possible when the object to be recovered is sufficiently sparse
      in a known basis. Currently, the best known sparsity-undersampling tradeoff is
      achieved when reconstructing by convex optimization, which is expensive in
      important large-scale applications. Fast iterative thresholding algorithms have
      been intensively studied as alternatives to convex optimization for large-scale
      problems. Unfortunately known fast algorithms offer substantially worse sparsity
      undersampling tradeoffs than convex optimization. We introduce a simple costless
      modification to iterative thresholding making the sparsity-undersampling tradeoff
      of the new algorithms equivalent to that of the corresponding convex optimization
      procedures. The new iterative-thresholding algorithms are inspired by belief
      propagation in graphical models. Our empirical measurements of the sparsity
      undersampling tradeoff for the new algorithms agree with theoretical
      calculations. We show that a state evolution formalism correctly derives the true
      sparsity-undersampling tradeoff. There is a surprising agreement between earlier
      calculations based on random convex polytopes and this apparently very different
      theoretical formalism.

PMID- 19858496
TI  - A sequence-compatible amount of native burial information is sufficient for
      determining the structure of small globular proteins.
AB  - Protein tertiary structures are known to be encoded in amino acid sequences, but
      the problem of structure prediction from sequence continues to be a challenge.
      With this question in mind, recent simulations have shown that atomic burials, as
      expressed by atom distances to the molecular geometrical center, are sufficiently
      informative for determining native conformations of small globular proteins. Here
      we use a simple computational experiment to estimate the amount of this required
      burial information and find it to be surprisingly small, actually comparable with
      the stringent limit imposed by sequence statistics. Atomic burials appear to
      satisfy, therefore, minimal requirements for a putative dominating property in
      the folding code because they provide an amount of information sufficiently large
      for structural determination but, at the same time, sufficiently small to be
      encodable in sequences. In a simple analogy with human communication, atomic
      burials could correspond to the actual "language" encoded in the amino acid
      "script" from which the complexity of native conformations is recovered during
      the folding process.

PMID- 19858497
TI  - The dynamics of adaptation on correlated fitness landscapes.
AB  - Evolutionary theory predicts that a population in a new environment will
      accumulate adaptive substitutions, but precisely how they accumulate is poorly
      understood. The dynamics of adaptation depend on the underlying fitness
      landscape. Virtually nothing is known about fitness landscapes in nature, and few
      methods allow us to infer the landscape from empirical data. With a view toward
      this inference problem, we have developed a theory that, in the weak-mutation
      limit, predicts how a population's mean fitness and the number of accumulated
      substitutions are expected to increase over time, depending on the underlying
      fitness landscape. We find that fitness and substitution trajectories depend not
      on the full distribution of fitness effects of available mutations but rather on
      the expected fixation probability and the expected fitness increment of
      mutations. We introduce a scheme that classifies landscapes in terms of the
      qualitative evolutionary dynamics they produce. We show that linear substitution
      trajectories, long considered the hallmark of neutral evolution, can arise even
      when mutations are strongly selected. Our results provide a basis for
      understanding the dynamics of adaptation and for inferring properties of an
      organism's fitness landscape from temporal data. Applying these methods to data
      from a long-term experiment, we infer the sign and strength of epistasis among
      beneficial mutations in the Escherichia coli genome.

PMID- 19858498
TI  - The differential activities of Runx1 promoters define milestones during embryonic
      hematopoiesis.
AB  - The transcription factor RUNX1/AML1 is a master regulator of hematopoietic
      development. Its spatiotemporal expression is tightly regulated during embryonic
      development and is under the control of 2 alternative promoters, distal and
      proximal. Despite the functional significance of Runx1, the relative and specific
      activities of these 2 promoters remain largely uncharacterized. To investigate
      these activities, we introduced 2 reporter genes under the control of the
      proximal and distal promoters in embryonic stem cell and transgenic mouse lines.
      Our study reveals that both in vitro and in vivo the proximal Runx1 isoform marks
      a hemogenic endothelium cell population, whereas the subsequent expression of
      distal Runx1 defines fully committed definitive hematopoietic progenitors.
      Interestingly, hematopoietic commitment in distal Runx1 knockout embryos appears
      normal. Altogether, our data demonstrate that the differential activities of the
      2 Runx1 promoters define milestones of hematopoietic development and suggest that
      the proximal isoform plays a critical role in the generation of hematopoietic
      cells from hemogenic endothelium. Identification and access to the discrete
      stages of hematopoietic development defined by the activities of the Runx1
      promoters will provide the opportunity to further explore the cellular and
      molecular mechanisms of hematopoietic development.

PMID- 19858500
TI  - Mapping the modified Rankin scale (mRS) measurement into the generic EuroQol (EQ
      5D) health outcome.
AB  - BACKGROUND: Mapping disease-specific instruments into generic health outcomes or
      utility values is an expanding field of interest in health economics. This
      article constructs an algorithm to translate the modified Rankin scale (mRS) into
      EQ-5D utility values. METHODS: mRS and EQ-5D information was derived from stroke
      or transient ischemic attack (TIA) patients identified as part of the Oxford
      Vascular study (OXVASC). Ordinary least squares (OLS) regression was used to
      predict UK EQ-5D tariffs from mRS scores. An alternative method, using
      multinomial logistic regression with a Monte Carlo simulation approach (MLogit)
      to predict responses to each EQ-5D question, was also explored. The performance
      of the models was compared according to the magnitude of their predicted-to
      actual mean EQ-5D tariff difference, their mean absolute and mean squared errors
      (MAE and MSE), and associated 95% confidence intervals (CIs). Out-of-sample
      validation was carried out in a subset of coronary disease and peripheral
      vascular disease (PVD) patients also identified as part of OXVASC but not used in
      the original estimation. RESULTS: The OLS and MLogit yielded similar MAE and MSE
      in the internal and external validation data sets. Both approaches also
      underestimated the uncertainty around the actual mean EQ-5D tariff producing
      tighter 95% CIs in both data sets. CONCLUSIONS: The choice of algorithm will be
      dependent on the study aim. Individuals outside the United Kingdom may find it
      more useful to use the multinomial results, which can be used with different
      country-specific tariff valuations. However, these algorithms should not replace
      prospective collection of utility data.

PMID- 19858499
TI  - Interlaboratory study characterizing a yeast performance standard for
      benchmarking LC-MS platform performance.
AB  - Optimal performance of LC-MS/MS platforms is critical to generating high quality
      proteomics data. Although individual laboratories have developed quality control
      samples, there is no widely available performance standard of biological
      complexity (and associated reference data sets) for benchmarking of platform
      performance for analysis of complex biological proteomes across different
      laboratories in the community. Individual preparations of the yeast Saccharomyces
      cerevisiae proteome have been used extensively by laboratories in the proteomics
      community to characterize LC-MS platform performance. The yeast proteome is
      uniquely attractive as a performance standard because it is the most extensively
      characterized complex biological proteome and the only one associated with
      several large scale studies estimating the abundance of all detectable proteins.
      In this study, we describe a standard operating protocol for large scale
      production of the yeast performance standard and offer aliquots to the community
      through the National Institute of Standards and Technology where the yeast
      proteome is under development as a certified reference material to meet the long
      term needs of the community. Using a series of metrics that characterize LC-MS
      performance, we provide a reference data set demonstrating typical performance of
      commonly used ion trap instrument platforms in expert laboratories; the results
      provide a basis for laboratories to benchmark their own performance, to improve
      upon current methods, and to evaluate new technologies. Additionally, we
      demonstrate how the yeast reference, spiked with human proteins, can be used to
      benchmark the power of proteomics platforms for detection of differentially
      expressed proteins at different levels of concentration in a complex matrix,
      thereby providing a metric to evaluate and minimize pre-analytical and analytical
      variation in comparative proteomics experiments.

PMID- 19858501
TI  - Unintended hepatic adverse events associated with cancer chemotherapy.
AB  - Chemotherapy is meant to be toxic, but it is particularly aimed at the tumor
      cells. Collateral damage may occur to normal cells and tissues, especially if
      they are fairly rapidly regenerating, as is the case for bone marrow cells,
      intestinal epithelial cells, and liver cells after hepatic injury. The liver has
      a great capacity to resist injury, overcome it, and to regenerate, even after
      quite massive injury (resection of 50%-65%, for example). This capacity may make
      it susceptible to chemotherapeutic toxicity, and a struggle between injury and
      adaptation, leading to recovery and tolerance or to failure and death. If the
      chemotherapy is aimed just at delaying progression of the cancer for a few weeks
      or months, it may not be worth the risk of irreversible liver injury developing
      in that time. Close clinical observation and sound clinical judgment are
      required.

PMID- 19858502
TI  - What a difference a word makes.

PMID- 19858503
TI  - Nursing science quarterly Best Paper Award: 2009.

PMID- 19858504
TI  - Theorizing family: a uniquely nursing perspective.

PMID- 19858505
TI  - The humanbecoming family model.
AB  - The purpose of this paper is to set forth the humanbecoming family model as an
      alternative view of family. The essences, paradoxes, and processes offer a unique
      way of envisioning family.

PMID- 19858506
TI  - Metaphor: creative energy informing nursing research.

PMID- 19858507
TI  - Expressiveness and creativeness: metaphorical images of nursing.
AB  - Metaphors are a personal expression and form of self-awareness, providing a way
      of describing an experience with dissimilar concepts to convey meaning. Metaphors
      create new meaning and provide a deeper insight into the human spirit. They are
      grounded in reality and day-to-day life experiences. Reflective practitioners
      incorporate and integrate their vast knowledge base of experience, skills, and
      attitudes to assist in formulating their practice as a metaphor. It is through
      this experience and reflection that nurses can creatively express their images of
      self and nursing.

PMID- 19858508
TI  - Common metaphors in nursing ethics.
AB  - Metaphors are literary comparisons that are used to create new meaning and
      insight for concepts, ideas, and situations found in a discipline. This author
      describes some common moral metaphors used in the discipline of nursing and
      specifically in situations of nursing ethics. New insights and questions for
      common usage are offered for the metaphors from a nursing theoretical
      perspective. Implications for nursing as a discipline are incorporated and
      discussion points for the future practice of nursing are illuminated.

PMID- 19858509
TI  - Fostering the creative spirit in teaching-learning.
AB  - This author describes creativity and the development of several curriculum
      projects fostering the creative spirit in the nursing academy as well as in other
      health sciences. It introduces Dr. Barbara Condon's column describing the use of
      artistic expression, framed by the humanbecoming school of thought, in a senior
      level nursing course at Briar Cliff University.

PMID- 19858510
TI  - Artistic expression in teaching-learning.
AB  - The use of art to enhance teaching-learning in nursing has proven beneficial in
      the past. While there are variety of methods to utilize art in education that
      exist, the author discusses artistic expression, as described by the
      humanbecoming school of thought, being used for the first time during the final
      term of the senior year for nursing students. This artistic expression was part
      of a variety of assignments connected to the students' preceptor experiences. The
      author in this column demonstrates a profound coming to know and personal
      enlightenment through a reflective process that accentuates the importance of not
      only allowing, but encouraging creativity throughout a nursing curriculum.

PMID- 19858511
TI  - Envisioning the possibles: living the art of humanbecoming with the leading
      following model in practice.

PMID- 19858512
TI  - The humanbecoming leading-following model in practice.
AB  - The purpose of this column is to illustrate how the humanbecoming leading
      following model was lived by nurses practicing within hospital, community, and
      school settings. The authors describe practice scenarios to show ways that nurses
      guided by the humanbecoming theory lived the processes and the key ideas of the
      model. One example addresses a change of policy, as the nurse lived the
      humanbecoming beliefs and values in leading-following. This column is nursing
      theory-guided evidence-based practice.

PMID- 19858513
TI  - From theory to practice: caring science according to Watson and Brewer.
AB  - Caring science is presented by Jean Watson and Barbara Brewer through an
      interview and dialogue format. Jean Watson presents caring science and its
      philosophy and evolution and the impact of her model on nursing and other
      disciplines. Barbara Brewer addresses the implementation of the model in a Magnet
      hospital setting and describes how her leadership facilitated implementation.

PMID- 19858514
TI  - Feeling fear: a humanbecoming study of older adults.
AB  - The purpose of this study is to enhance understanding of the lived experience of
      feeling fear. Parse's phenomenological-hermeneutic method was used to answer the
      research question: What is the structure of the lived experience of feeling fear?
      Ten older adults living in or near New York City participated in the study. Data
      were collected through dialogical engagement and analyzed through the extraction
      synthesis processes. Core concepts were identified and discussed. The structure,
      feeling fear is haunting possibilities with cautious perseverance arising with
      reassuring affiliations amid defiance, is the central finding of this study. This
      finding was connected to the humanbecoming theory and extant literature,
      contributing to nursing knowledge, expanding the theory, and enhancing of
      understanding about feeling fear with older adults.

PMID- 19858515
TI  - Toward understanding and measuring adaptation level in the context of the Roy
      adaptation model.
AB  - The Roy adaptation model concepts of stimuli, coping mechanisms, and modes of
      adaptation have been translated into several middle-range concepts and measured
      using existing and new instruments. The concept of adaptation level, however, has
      rarely been used in Roy adaptation model-based research. This paper presents a
      description of how the Roy adaptation model concept of adaptation level was
      translated into the logically congruent middle-range theory concept of
      adjustment. A single-item instrument, the Adjustment Scale, is identified as one
      way to measure adjustment.

PMID- 19858516
TI  - Participatory dreaming: a conceptual exploration from a unitary appreciative
      inquiry perspective.
AB  - Dreaming is a universal phenomenon in human experience and one that carries
      multiple meanings in the narrative discourse across disciplines. Dreams can be
      collective, communal, and emancipatory, as well as individual. While individual
      dreaming has been extensively studied in the literature, the participatory nature
      of dreaming as a unitary phenomenon is limited. The concept of participatory
      dreaming within a unitary appreciative framework for healing is explored from
      perspectives in anthropology, psychology, and nursing. A participatory model of
      dreaming is proposed from a synthesis of the literature for use in future
      research using unitary appreciative inquiry.

PMID- 19858517
TI  - Improving the profession of nursing in Slovenia.
AB  - The importance of increasing the educational attainment of professional nurses in
      Slovenia is discussed. It is suggested that with the global economic recession it
      is more, not less, important that professional nurses are competent and
      independent practitioners.

PMID- 19858518
TI  - Nursing professionalism in Slovenia: knowledge, power, and ethics.
AB  - The purpose of this column is to conceptualize nursing professionalism in
      Slovenia as a mutual process between social change and the education of
      professional nurses. The process of educating professional nurses in Slovenia
      occurs in a changing social and organizational context. As the complexity and
      speed of change increases it is becoming increasingly essential for all nurses to
      have expert knowledge, skills, and competencies. The author also aims to present
      the autonomy of new healthcare and the new theoretical concept of nursing as
      scientific human capital in Slovenia.

PMID- 19858519
TI  - To defile by assuming to know.

PMID- 19858520
TI  - Caring for older adults: the parables in Confucian texts.

PMID- 19858521
TI  - Leadership and ethics in nurse-nurse relationships.

PMID- 19858522
TI  - Basic science is not nursing research? If it isn't, what is?

PMID- 19858523
TI  - Hypothalamic--pituitary-- adrenal axis dysregulation in women with irritable
      bowel syndrome in response to acute physical stress.
AB  - Irritable bowel syndrome (IBS) supports the concept of a dysregulated
      hypothalamic-pituitary-adrenal (HPA) axis. This study investigates the
      neuroendocrine and psychological responses to the acute physical stress of a
      lumbar puncture (LP) in women with diarrhea-predominant IBS by assessing central
      and peripheral HPA activity and affective measures. Blood samples have been
      collected at baseline and immediately post- and 1 hr following LP from 13 women
      with IBS and 13 controls. Plasma adrenocorticotropic hormone (ACTH), cortisol,
      epinephrine, and norepinephrine levels are analyzed. A single measure of
      cerebrospinal fluid (CSF) concentrations of corticotropin-releasing factor
      (CRF(CSF)) and norepinephrine(CSF) is noted. Affective assessments are used to
      rate anxiety and depression with the Hospital Anxiety and Depression Scale (HADS)
      and acute mood state is rated using the Stress Symptom Rating questionnaire
      (stress, anxiety, anger, arousal). The women with IBS display blunted ACTH and
      cortisol responses to the LP along with a profile of affective responsiveness
      suggestive of chronic psychosocial stress, although no CRF(CSF) differences
      between groups are observed.

PMID- 19858524
TI  - Academic, social, and behavioral outcomes at age 12 of infants born preterm.
AB  - The effects of gradient levels of perinatal morbidity on school outcomes have
      been investigated at age 12 in four preterm groups, classified as healthy (no
      medical or neurological illness), medical morbidity, neurological morbidity, and
      small-for-gestational-age (SGA), and a full-term comparison group. Teachers
      report on academic competence, social skills, and problem behaviors. Data on
      school type, classroom setting, and school service use are gathered from school
      records. Preterm groups are found to be equivalent to full-term peers in social
      skills and problem behavior. Preterm groups with neurological and SGA morbidity
      have the lowest academic competence scores. Unexpectedly, preterm infants with
      medical morbidity have higher academic competence scores compared with the other
      preterm groups. School service use increases with greater perinatal morbidity and
      is contingent on multiple rather than single indicators of perinatal morbidity.
      Continued monitoring of preterm infants through early adolescence will ensure
      that appropriate school services and resources are available to maximize their
      school success.

PMID- 19858525
TI  - Predictors of self-efficacy to use condoms among seropositive middle-aged African
      American men.
AB  - Condom use during sexual encounters continues to be a challenge for seropositive
      individuals. Hence, the influence of personal characteristics, AIDS knowledge,
      and religious well-being on perceived self-efficacy to use condoms has been
      examined in a convenience nonprobabilistic sample of 130 middle-aged seropositive
      African American men from the Mid-Atlantic region. AIDS knowledge and religious
      well-being are strongly related to self-efficacy to use condoms. These findings
      indicate that it is critical to explore further the relationship of AIDS
      knowledge and religious well-being with self-efficacy to use condoms.

PMID- 19858526
TI  - A case of chronic fatigue syndrome triggered by influenza H1N1 (swine influenza).
AB  - This case report describes an adolescent boy who was diagnosed as suffering from
      chronic fatigue syndrome 5 months after infection with H1N1 influenza.

PMID- 19858527
TI  - Recent advances in understanding the molecular basis of Paget disease of bone.
AB  - Paget disease of bone (PDB) is a relatively common disorder characterised by
      increased bone turnover within discrete lesions throughout the skeleton. The
      condition has a strong genetic component, with mutations affecting the SQSTM1
      gene that encodes the p62 protein often found in PDB patients, although
      environmental factors also play an important role in disease aetiology. The
      precise disease mechanism(s) in familial forms and sporadic forms of PDB is
      unclear, although defective RANK-NF-kappaB signalling has been suggested to
      contribute to the increased activity of pagetic osteoclasts in the former. Here,
      there is a review of recent advances in the understanding of the molecular basis
      of PDB with particular emphasis on findings since 2008, and focus on newly
      defined functions of the p62 protein upon which SQSTM1 mutations may impact in
      the development of the pagetic phenotype.

PMID- 19858528
TI  - Heart transplant biopsies: interpretation and significance.
AB  - The endomyocardial biopsy (EMB) is a valuable tool that is inadequately utilised,
      except in monitoring orthotopic, homograft, heart grafts. Performed on a regular,
      programmed schedule, or on an emergent basis when needed, the EMB is the gold
      standard for monitoring graft function ( with regard to cellular rejection),
      often before clinical symptoms develop. This paper addresses these points and
      discusses handling of tissues and some studies for possible antibody mediated
      rejection when the lack of morphologic features of cellular rejection does not
      fit with the patients clinical presentation, days or months after the surgical
      procedure. In the hands of a skilled operator the EMB procedure is relatively
      painless and free of significant complications.

PMID- 19858529
TI  - Signature sequence validation of human papillomavirus type 16 (HPV-16) in
      clinical specimens.
AB  - AIMS: Persistent infection indicated by detection of human papillomavirus 16 (HPV
      16) on repeat testing over a period of time poses the greatest cervical cancer
      risk. However, variants of HPV-16, HPV-31 and HPV-33 may share several short
      sequence homologies in the hypervariable L1 gene commonly targeted for HPV
      genotyping. The purpose of this study was to introduce a robust laboratory
      procedure to validate HPV-16 detected in clinical specimens, using the GenBank
      sequence database as the standard reference for genotyping. METHODS: A nested PCR
      with two pairs of consensus primers was used to amplify the HPV DNA released in
      crude proteinase K digest of the cervicovaginal cells in liquid-based
      Papanicolaou cytology specimens. The positive nested PCR products were used for
      direct automated DNA sequencing. RESULTS: A 48-base sequence downstream of the
      GP5+ priming site, or a 34-base sequence upstream thereof, was needed for
      unequivocal validation of an HPV-16 isolate. Selection of a 45-base, or shorter,
      sequence immediately downstream of the GP5+ site for Basic Local Alignment Search
      Tool sequence analysis invariably led to ambiguous genotyping results.
      CONCLUSIONS: DNA sequence analysis may be used for differential genotyping of HPV
      16, HPV-31 and HPV-33 in clinical specimens. However, selection of the signature
      sequence for Basic Local Alignment Search Tool algorithms is crucial to
      distinguish certain HPV-16 variants from other closely related HPV genotypes.

PMID- 19858530
TI  - A case of Staphylococcus aureus septicaemia following platelet transfusion.
AB  - Platelet transfusions have the highest incidence of post-transfusion sepsis
      compared with any other blood products. Recent reports suggest that platelet
      related bacteraemia occurs at a frequency of approximately 50 times greater than
      that for red blood cells. The source is usually skin contaminants from the donor
      and several organisms have been implicated, the commonest of which are coagulase
      negative staphylococci. This report describes a case of serious Staphylococcus
      aureus sepsis following platelet transfusion, and discusses relevant methods to
      detect and prevent bacterial contamination of blood products.

PMID- 19858531
TI  - Approach to a lung transplant biopsy.
AB  - With increasing numbers of lung transplants being performed worldwide, lung
      transplant allograft biopsies are becoming increasingly common. The evaluation of
      lung transplant biopsies typically focuses on the assessment of allograft
      rejection and infection, but other entities may also be seen in biopsy material.
      Presented here is an approach to lung transplant biopsies, in which there is an
      overview major diagnostic entities that may be encountered and discussion of
      findings that may present interpretive challenges.

PMID- 19858532
TI  - Trends in Down's syndrome live births and antenatal diagnoses in England and
      Wales from 1989 to 2008: analysis of data from the National Down Syndrome
      Cytogenetic Register.
AB  - OBJECTIVES: To describe trends in the numbers of Down's syndrome live births and
      antenatal diagnoses in England and Wales from 1989 to 2008. Design and setting
      The National Down Syndrome Cytogenetic Register holds details of 26488 antenatal
      and postnatal diagnoses of Down's syndrome made by all cytogenetic laboratories
      in England and Wales since 1989. INTERVENTIONS: Antenatal screening, diagnosis,
      and subsequent termination of Down's syndrome pregnancies. MAIN OUTCOME MEASURES:
      The number of live births with Down's syndrome. RESULTS: Despite the number of
      births in 1989/90 being similar to that in 2007/8, antenatal and postnatal
      diagnoses of Down's syndrome increased by 71% (from 1075 in 1989/90 to 1843 in
      2007/8). However, numbers of live births with Down's syndrome fell by 1% (752 to
      743; 1.10 to 1.08 per 1000 births) because of antenatal screening and subsequent
      terminations. In the absence of such screening, numbers of live births with
      Down's syndrome would have increased by 48% (from 959 to 1422), since couples are
      starting families at an older age. Among mothers aged 37 years and older, a
      consistent 70% of affected pregnancies were diagnosed antenatally. In younger
      mothers, the proportions of pregnancies diagnosed antenatally increased from 3%
      to 43% owing to improvements in the availability and sensitivity of screening
      tests. CONCLUSIONS: Since 1989, expansion of and improvements in antenatal
      screening have offset an increase in Down's syndrome resulting from rising
      maternal age. The proportion of antenatal diagnoses has increased most strikingly
      in younger women, whereas that in older women has stayed relatively constant.
      This trend suggests that, even with future improvements in screening, a large
      number of births with Down's syndrome are still likely, and that monitoring of
      the numbers of babies born with Down's syndrome is essential to ensure adequate
      provision for their needs.

PMID- 19858533
TI  - Mortality among residents of shelters, rooming houses, and hotels in Canada: 11
      year follow-up study.
AB  - OBJECTIVE: To examine mortality in a representative nationwide sample of homeless
      and marginally housed people living in shelters, rooming houses, and hotels.
      DESIGN: Follow-up study. SETTING: Canada 1991-2001. PARTICIPANTS: 15 100 homeless
      and marginally housed people enumerated in 1991 census. MAIN OUTCOME MEASURES:
      Age specific and age standardised mortality rates, remaining life expectancies at
      age 25, and probabilities of survival from age 25 to 75. Data were compared with
      data from the poorest and richest income fifths as well as with data for the
      entire cohort RESULTS: Of the homeless and marginally housed people, 3280 died.
      Mortality rates among these people were substantially higher than rates in the
      poorest income fifth, with the highest rate ratios seen at younger ages. Among
      those who were homeless or marginally housed, the probability of survival to age
      75 was 32% (95% confidence interval 30% to 34%) in men and 60% (56% to 63%) in
      women. Remaining life expectancy at age 25 was 42 years (42 to 43) and 52 years
      (50 to 53), respectively. Compared with the entire cohort, mortality rate ratios
      for men and women, respectively, were 11.5 (8.8 to 15.0) and 9.2 (5.5 to 15.2)
      for drug related deaths, 6.4 (5.3 to 7.7) and 8.2 (5.0 to 13.4) for alcohol
      related deaths, 4.8 (3.9 to 5.9) and 3.8 (2.7 to 5.4) for mental disorders, and
      2.3 (1.8 to 3.1) and 5.6 (3.2 to 9.6) for suicide. For both sexes, the largest
      differences in mortality rates were for smoking related diseases, ischaemic heart
      disease, and respiratory diseases. CONCLUSIONS: Living in shelters, rooming
      houses, and hotels is associated with much higher mortality than expected on the
      basis of low income alone. Reducing the excessively high rates of premature
      mortality in this population would require interventions to address deaths
      related to smoking, alcohol, and drugs, and mental disorders and suicide, among
      other causes.

PMID- 19858534
TI  - Hepatitis C testing in sexual health services in England, 2002-7: results from
      sentinel surveillance.
AB  - OBJECTIVES: To describe testing for hepatitis C virus (HCV) in sexual health
      services in England between 2002 and 2007, using data from a sentinel
      surveillance study of hepatitis testing. METHODS: Data on all anti-HCV tests
      carried out between 2002 and 2007 were collected from 20 participating
      laboratories. Test requests originating in sexual health services were
      identified, allowing analysis of the demographic and clinical characteristics of
      individuals tested in this setting. KC60 statutory returns data were used to
      estimate the proportion of new genitourinary medicine clinic attendees tested for
      hepatitis C each year. RESULTS: 90 424 individuals were tested for anti-HCV in
      100 sexual health clinics; 3.2% (n=2858) were found to be positive. Multivariable
      analysis showed anti-HCV status to be associated with male sex and a reported
      history of injecting drug use. In those clinics for which data on trends were
      available, testing for anti-HCV increased over the study period and the
      percentage testing positive decreased. KC60 data suggested that most clinics
      tested less than 20% of new patients for anti-HCV, although the proportion of
      patients tested increased over time. CONCLUSIONS: Sexual health services have
      become increasingly important locations for hepatitis C testing in England,
      although the proportion of patients testing positive is low compared with other
      settings. We suggest that testing in this setting could be better targeted to
      those most at risk of infection by thorough investigation of risk factors among
      service users.

PMID- 19858535
TI  - Increased risk of oesophageal adenocarcinoma among upstream petroleum workers.
AB  - OBJECTIVES: To investigate cancer risk, particularly oesophageal cancer, among
      male upstream petroleum workers offshore potentially exposed to various
      carcinogenic agents. METHODS: Using the Norwegian Registry of Employers and
      Employees, 24 765 male offshore workers registered from 1981 to 2003 was compared
      with 283 002 male referents from the general working population matched by age
      and community of residence. The historical cohort was linked to the Cancer
      Registry of Norway and the Norwegian Cause of Death Registry. RESULTS: Male
      offshore workers had excess risk of oesophageal cancer (RR 2.6, 95% CI 1.4 to
      4.8) compared with the reference population. Only the adenocarcinoma type had a
      significantly increased risk (RR 2.7, 95% CI 1.0 to 7.0), mainly because of an
      increased risk among upstream operators (RR 4.3, 95% CI 1.3 to 14.5). Upstream
      operators did not have significant excess of respiratory system or colon cancer
      or mortality from any other lifestyle-related diseases investigated. CONCLUSION:
      We found a fourfold excess risk of oesophageal adenocarcinoma among male workers
      assumed to have had the most extensive contact with crude oil. Due to the small
      number of cases, and a lack of detailed data on occupational exposure and
      lifestyle factors associated with oesophageal adenocarcinoma, the results must be
      interpreted with caution. Nevertheless, given the low risk of lifestyle-related
      cancers and causes of death in this working group, the results add to the
      observations in other low-powered studies on oesophageal cancer, further
      suggesting that factors related to the petroleum stream or carcinogenic agents
      used in the production process might be associated with risk of oesophageal
      adenocarcinoma.

PMID- 19858536
TI  - High frequency of fumigants and other toxic gases in imported freight containers-
      an underestimated occupational and community health risk.
AB  - Residues of pesticide fumigants and toxic industrial chemicals in freight
      containers represent a health hazard to employees and consumers, especially since
      freight containers are sealed for transport and distributed widely throughout the
      importing countries before being opened for unloading. We investigated 2113
      freight containers arriving at the second largest container terminal in Europe,
      Hamburg, Germany, over a 10-week period in 2006. The countries of origin, type of
      contents and the pesticide fumigation history declared on labels attached to the
      container were recorded. We determined that 1478 (70%) containers were
      contaminated with toxic chemicals above chronic reference exposure levels; 761
      (36%) even exceeded the higher acute reference exposure level thresholds. Benzene
      and/or formaldehyde contamination was 4-times greater than for fumigants. Our
      findings indicate a health risk for dockworkers, container unloaders and even end
      consumers, especially as many of the cancerogenic or toxic gases elude subjective
      detection.

PMID- 19858537
TI  - Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are
      associated with serum levels of mesothelin-related protein.
AB  - BACKGROUND: Serum mesothelin, also known as soluble mesothelin-related protein
      (SMRP), reportedly shows increased levels in epithelial-type malignant pleural
      mesothelioma, but sometimes also arrives at high values in healthy asbestos
      exposed subjects. OBJECTIVES: This study aimed to investigate whether single
      nucleotide polymorphisms in the 3'untranslated region (3'UTR) of the mesothelin
      encoded gene (MSLN) are associated with the SMRP levels measured in serum.
      METHODS: The 3'UTR of the mesothelin gene was genotyped in 59 healthy asbestos
      exposed subjects, selected on the basis of their SMRP levels. Direct sequencing
      did not show any new polymorphism, but enabled us to genotype two known SNPs
      (rs1057147, rs57272256). Differences in the mean values of SMRP in wild-type and
      variant heterozygote groups were calculated. RESULTS: High levels of SMRP in
      healthy asbestos-exposed subjects were significantly associated with polymorphism
      rs1057147 (G<A). Regarding rs57272256, there was no statistically significant
      difference between wild-type and heterozygote groups. Our study suggests that
      rs1057147 polymorphism can affect mesothelin expression. Although these data need
      to be confirmed with a larger number of cases, this study warrants further
      research in order to better understand the relationship between mesothelin
      polymorphisms and SMRP.

PMID- 19858538
TI  - Early treatment with, and time receiving, first disease-modifying antirheumatic
      drug predicts long-term function in patients with inflammatory polyarthritis.
AB  - OBJECTIVES: To investigate the influence of early disease-modifying antirheumatic
      drug (DMARD) treatment on long-term functional outcome in patients with recent
      onset inflammatory polyarthritis (IP), and the impact of the duration of first
      and subsequent DMARD treatment. METHODS: 642 subjects from a primary care
      registry of patients with new-onset IP, recruited 1990-4, were followed up for 10
      years. Mean change in Health Assessment Questionnaire (HAQ) scores between
      baseline and 10 years were compared by time to, and time receiving, first DMARD
      treatment and total time receiving treatment, using linear regression. Adjustment
      for time-dependent confounders and censoring was performed using marginal
      structural weights. RESULTS: When adjusted for baseline and subsequent disease
      severity, those treated early (<6 months from symptom onset) experienced a non
      significant improvement in function compared with those never treated (adjusted
      mean difference in change (adj_MDIC) in HAQ -0.24; 95% CI -0.58 to 0.09); and a
      significant benefit for each additional month of treatment within 6 months of the
      onset of symptoms (adj_MDIC -0.10; 95% CI -0.19 to -0.02). Patients who
      discontinued their first DMARD within 6 months experienced a significant
      deterioration in long-term function (adj_MDIC in HAQ 0.28; 95% CI 0.04 to 0.52),
      while those who continued their first treatment for > 3 years experienced an
      improvement (adj_MDIC in HAQ -0.37; 95% CI -0.77 to 0.04). CONCLUSIONS: The
      importance of time to, and response to, first DMARD treatment and total duration
      of DMARD treatment in modifying the 10-year function in patients with IP has been
      demonstrated.

PMID- 19858539
TI  - Impact of heat on mortality in 15 European cities: attributable deaths under
      different weather scenarios.
AB  - BACKGROUND: High ambient summer temperatures have been shown to influence daily
      mortality in cities across Europe. Quantification of the population mortality
      burden attributable to heat is crucial to the development of adaptive approaches.
      The impact of summer heat on mortality for 15 European cities during the 1990s
      was evaluated, under hypothetical temperature scenarios warmer and cooler than
      the mean and under future scenarios derived from the Intergovernmental Panel on
      Climate Change Special Report on Emission Scenarios (SRES). METHODS: A Monte
      Carlo approach was used to estimate the number of deaths attributable to heat for
      each city. These estimates rely on the results of a Bayesian random-effects meta
      analysis that combines city-specific heat-mortality functions. RESULTS: The
      number of heat-attributable deaths per summer ranged from 0 in Dublin to 423 in
      Paris. The mean attributable fraction of deaths was around 2%. The highest impact
      was in three Mediterranean cities (Barcelona, Rome and Valencia) and in two
      continental cities (Paris and Budapest). The largest impact was on persons over
      75 years; however, in some cities, important proportions of heat-attributable
      deaths were also found for younger adults. Heat-attributable deaths markedly
      increased under warming scenarios. The impact under SRES scenarios was slightly
      lower or comparable to the impact during the observed hottest year. CONCLUSIONS:
      Current high summer ambient temperatures have an important impact on European
      population health. This impact is expected to increase in the future, according
      to the projected increase of mean ambient temperatures and frequency, intensity
      and duration of heat waves.

PMID- 19858540
TI  - Residential density and adolescent overweight in a rapidly urbanising region of
      Mainland China.
AB  - OBJECTIVE: This study investigated the association of residential density with
      overweight among adolescents in an urban area of China. METHODS: Using multistage
      proportional sampling methods, a population-based cross-sectional study was
      conducted in Nanjing between September and November 2004 (n=2375; mean age=13.9
      +/- 1.0 years old; 46.2% boys; survey response rate=89.3%). Body mass index was
      calculated from self-reported body weight and height. Overweight, the main
      outcome variable, was defined as a BMI >=85 percentile value for age- and gender
      specific reference data according to the recommendation for Chinese adolescents.
      The primary explanatory variable was the residential density of the urban
      districts. Mixed-effects logistic regression models were used for the analysis.
      RESULTS: Students in the higher and middle tertiles of residential density had a
      2.17-fold (95% CI 1.41 to 3.33) and 1.89-fold (95% CI 1.22 to 2.92) higher
      likelihood of being overweight, respectively, compared with those in the lower
      tertile. The associations were slightly attenuated but still significant after
      adjusting for time spent in recreational physical activity and sedentary
      behaviour (viewing TV and sitting for academic study). CONCLUSIONS: Residential
      density was positively associated with overweight among urban Chinese
      adolescents. Our findings warrant further research examining attributes of urban
      environments associated with adolescents' obesity in China and potential
      mechanisms between them.

PMID- 19858541
TI  - Parental psychopathology and socioeconomic position predict adolescent
      offspring's mental health independently and do not interact: the TRAILS study.
AB  - BACKGROUND: Familial risk factors have been implicated in the development of
      mental health problems in adolescents. Whether the associations between parental
      loading, as assessed by lifetime psychopathology, and offspring internalising and
      externalising problems were moderated by family socioeconomic position (SEP) was
      investigated. Two hypotheses of moderation were tested: (1) the "social push"
      hypothesis in which parental loading effects are stronger in contexts with low
      environmental risks and (2) the "vulnerability" hypothesis in which parental
      loading effects are stronger in high-risk environments. METHOD: In a population
      based sample of 2149, familial loading and family SEP were assessed at baseline
      by parent reports. Offspring psychopathology was assessed by reports from
      multiple informants (parent, self and teachers). Multiple linear regression was
      used to assess the independent associations of parental loading and family SEP on
      offspring psychopathology and their potential interaction. RESULTS: Both family
      SEP and familial loading had significant independent main effects on offspring
      internalising and externalising problems. However, the interaction terms were not
      significant and did not add any explanatory power to the model. CONCLUSIONS:
      Lower levels of family SEP appear not to confer additional risks for mental
      health problems in offspring of parents with high loading on psychopathology.
      During early adolescence, parental psychopathology and low family SEP seem
      independent risk factors for offspring mental health problems. Results do not
      support either the social push or vulnerability hypothesis as no evidence of
      interactions between parental loading and family SEP were found.

PMID- 19858542
TI  - The influence of social capital on health in eight former Soviet countries: why
      does it differ?
AB  - BACKGROUND: Previous research has identified the role of social capital in
      explaining variations in health in the countries of the former Soviet Union. This
      study explores whether the benefits of social capital vary among these countries
      and why. METHODS: The impact of micro social capital (trust, membership and
      social isolation) on individual health was estimated in each of eight former
      Soviet republics using instrumental variables to overcome methodological hazards
      such as endogeneity and reverse causality. Interactions with institutional
      variables (voice and accountability, effectiveness of the legal system, informal
      economy) and social protection variables (employment protection, old age and
      disability benefits, sickness and health benefits) were examined. RESULTS: Most
      social capital indicators, in most countries, are associated with better health
      but the magnitude and significance of the impact differ between countries. Some
      of this variation can be explained by interacting social capital indicators with
      measures of institutional quality, with membership of organisations bringing
      greater benefit for health in countries where civil liberties are stronger,
      whereas social isolation has more adverse consequences where there is a large
      informal economy. A lesser amount is explained by the interaction of social
      capital indicators with selected measures of social protection. CONCLUSION: When
      considering interventions to improve social capital as a means of improving
      population health, it seems advisable to take into account the influence of
      macrocontextual variables, in order not to overstate or understate the likely
      impact of the intervention.

PMID- 19858543
TI  - [The Reykjavik Medical Society at 100 years. Doctors and Society].

PMID- 19858544
TI  - [General health in Icelandic farmers].
AB  - BACKGROUND: There is a limited information on the general health of Icelandic
      farmers. It has been suggested that it might be worse than among other
      professions. This is thought to be in part because of the unique work environment
      of farmers.The aims of the study were to compare the general health of animal
      farmers with a group of non-farmers, and test the hypothesis that animal farmers
      overall have a better general health than non-farmers. METHODS: A cross sectional
      study of all animal farmers in Iceland operating running a farm of more than 100
      animal (sheep) units compared with a group of non-farmers. A total of 2042
      farmers were sent a detailed questionnaire concerning general health symptoms and
      doctor visits (response rate 54%). The comparison group consisted of 1500
      randomly chosen non-farming individuals (response rate 46%). RESULTS: Farmers
      comprised more males, were older and smoked less than non-farmers. When general
      health symptoms for the last 12 months were compared between farmers and non
      farmers, minor differences were noted. Farmers less commonly had restless legs,
      fatigue, diarrhea, allergy and hearing loss. There were no differences in doctor
      visits for many chronic diseases such as diabetes and hypertension despite the
      age difference between the groups. Repeated absence from work was less common
      among farmers and they had shorter sick leaves than comparison group.
      CONCLUSIONS: Minor differences were noted in general symptoms and doctor visits
      between farmers and non-farmers despite the fact that farmers were older. Absence
      from work for illness is less common among farmers. This study suggest that
      farmers general health is not worse than that of others.

PMID- 19858545
TI  - [Out-of-pocket health care expenditures among population groups in Iceland].
AB  - OBJECTIVE: Out-of-pocket health expenditures affect access to health care. The
      study investigated trends in these expenditures, and whether certain population
      groups spent more than others. MATERIAL AND METHODS: The data come from two
      national health surveys among Icelandic adults from 1998 and 2006. The response
      rate was 69% in the former survey (N=1924), and 60% in the latter (N= 1532).
      Average household health expenditures and household expenditure burden
      (expenditures as % of total household income) were compared over time and between
      groups. RESULTS: Household health expenditures increased by 29% in real terms
      between 1998 and 2006. The biggest items in 2006 were drugs and dental care.
      Women, younger and older individuals, the single and divorced, smaller
      households, the unemployed and non-employed, individuals with low education and
      income, the chronically ill, and the disabled, had the highest household
      expenditure burden. Comparison between 1998 and 2006 indicated increased
      expenditure burden among young people, students, the unemployed, and the least
      educated, but decreased burden among the elderly, the widowed, and parents of
      young children. CONCLUSIONS: Household health expenditures differ substantially
      between groups, suggesting reconsideration of current health insurance policies,
      especially with regard to disabled, non-employed, low-income, and young
      individuals.

PMID- 19858546
TI  - [Head and neck squamous cell cancer].
AB  - Head and neck squamous cell carcinoma (HNSCC) is relatively common and is
      strongly related to smoking and alcohol consumption but infection by human
      papillomavirus has also emerged as a risk factor for HNSCC. The treatment of
      these tumors is complicated and patients are best served by a multidisciplinary
      team. The therapy now commonly involves a multidisciplinary approach including
      surgery, radiation treatment and chemotherapy. Lower stage disease carries a
      relatively good prognosis. The treatment of metastatic HNSCC remains
      unsatisfactory and the prognosis of these patients is poor.

PMID- 19858547
TI  - [Scientific articles in the Icelandic Medical Journal 2004-2008: an overview].
AB  - INTRODUCTION: In the past 5 years the Icelandic Medical Journal has undergone
      many changes during a period of flourishing research in Iceland. The process of
      reviewing and editing scientific articles has been revised since the Journal
      joined the Medline database in 2005 and the proportion of rejected articles has
      risen. New columns have been launched covering medical history, professionalism,
      ethics and hobbies of the medical profession. MATERIAL AND METHODS: We
      categorized all scientific articles from the period 2004-2008, that is research
      articles, review articles, case reports and clinical guidelines, according to
      types of articles and to which medical speciality or subspeciality the
      publication should belong. RESULTS: The number of scientific articles rose during
      the period but the number of research articles remained around 20 most years
      during the period. The relative proportion of research articles therefore fell
      whereas the number and proportion of review articles and case reports increased.
      Clinical guidelines ceased to appear in the Journal. The contribution of
      individual specialities to the Journal varied widely. CONCLUSION: Researchers
      amongst doctors and related professions need be encouraged to submit scientific
      articles to the Journal. The publication of scientific articles in English in the
      web-based form of the Journal may prove to be stimulating in this regard for
      Icelandic doctors abroad as well as for some researchers in Iceland.

PMID- 19858548
TI  - [Case of the month. Candida Endophthalmitis].

PMID- 19858549
TI  - [Surgery for coarctation of the aorta in Iceland 1990-2006].
AB  - BACKGROUND AND AIMS: Coarctation of the aorta (CoA) is a congenital narrowing of
      the aorta, distal to the origin of the left subclavian artery. Treatment consists
      of surgical excision but balloon angioplasty is also a treatment option for
      selected patients. The aim of this study was to evaluate surgical outcome in
      children operated for CoA in Iceland. MATERIAL AND METHODS: All Icelandic
      children (<18 yrs.) operated for CoA in Iceland between 1990 and 2006. Patients
      operated abroad (n=17) or managed conservatively (n=12) were excluded. Mean
      follow up period was 8.5 +/- 4.3 years. RESULTS: Of 67 children diagnosed with
      CoA, 38 were operated on in Iceland (mean age 36 +/- 58 months, and 22 male and
      16 female patients), 10 required immediate surgery for cardiac failure and eight
      were diagnosed incidentally. Extended end-to-end anastomosis was the most common
      procedure (n=31). Subclavian-flap aortoplasty was performed in seven patients.
      Average operation time was 134 min. and mean aortic closure time was 21 +/- 9
      min. Hypertension (58%) and heart failure (11%) were the most common
      postoperative complications. Recoarctation developed 35 +/- 56 months after
      surgery in seven patients (18%) and was successfully treated with balloon
      angioplasty. There were no operative deaths and no patients developed paraplegia.
      One patient suffered an ischemic injury to the brachial plexus. Today all of the
      patients are alive, except for one patient that died four months after surgery
      from heart failure. CONCLUSION: Majority of Icelandic patients with CoA are
      operated on in Iceland with excellent outcome, both regarding short term
      complications and long term survival.

PMID- 19858550
TI  - [Defining the Icelandic Medical Journal].

PMID- 19858551
TI  - Linear and third-order nonlinear optical responses of multilayered Ag:Si3N4
      nanocomposites.
AB  - The linear and third-order nonlinear responses of tailored Si3N4/Ag/Si3N4
      trilayers and (Si3N4/Ag)n/Si3N4 multilayers grown by alternating ion-beam
      sputtering have been studied by combining complementary characterization
      techniques such as transmission electron microscopy, spectroscopic ellipsometry
      and degenerate four-wave mixing. The linear optical response dominated by the
      surface plasmon resonance of Ag nanoparticles has been measured over the whole
      visible range while the third-order nonlinear susceptibility has been probed at
      the surface plasmon resonance wavelength. Due to the weak in-plane interaction
      between Ag nanoparticles, the linear and nonlinear optical responses of the
      Si3N4/Ag/Si3N4 trilayers are mainly influenced by the size and shape of the
      nanoparticles. A maximum value of 1.1 x 10(-7) esu has been found at 635 nm for
      the effective third-order nonlinear susceptibility of the trilayer with the
      highest amount of silver. The linear optical response of the (Si3N4/Ag)n/Si3N4
      multilayers is shown to be dominated by the surface plasmon resonance of isolated
      layers of weakly interacting nanoparticles at wavelengths shorter than 600 nm
      whereas a contribution due to vertical interactions has been shown for higher
      wavelengths. Below the vertical percolation threshold, their nonlinear optical
      response at the surface plasmon resonance wavelength is similar to the one of an
      isolated assembly of nanoparticles, and the effective third-order nonlinear
      susceptibility is slightly increased by decreasing the thickness of the Si3N4
      spacer.

PMID- 19858552
TI  - Investigation of the carbon nanotube AFM tip contacts: free sliding versus pinned
      contact.
AB  - Mechanical response of carbon nanotube atomic force microscope probes are
      investigated using a thermal noise forcing. Thermal noise spectra are able to
      investigate mechanical behaviors that cannot be studied using classical atomic
      force microscope modes. Experimental results show that the carbon nanotube
      contacts can be classified in two categories: the free sliding and pinned cases.
      The pinned contact case requires the description of the cantilever flexural
      vibrations with support spring-coupled cantilever boundary conditions. Our
      experimental results show that carbon nanotubes exhibit different contact
      behaviors with a surface, and in turn different mechanical responses.

PMID- 19858553
TI  - Tuning of operation mode of ZnO nanowire field effect transistors by solvent
      driven surface treatment.
AB  - We report on the adjustment of the operation voltage in ZnO nanowire field effect
      transistors (FETs) by a simple solvent treatment. We have observed that by
      submerging ZnO nanowires in isopropyl alcohol (IPA), the surface of the ZnO
      nanowires is etched, generating surface roughness, and their defect emission peak
      becomes stronger. In particular, ZnO nanowire FETs before IPA treatment operate
      in the depletion-mode, but are converted to the enhancement-mode with a positive
      shift of threshold voltage after submersion in IPA. This solvent treatment can be
      a useful method for controlling the operation mode of ZnO nanowire FETs for wide
      applications of nanowire-based electronic devices and circuits.

PMID- 19858554
TI  - Volumetric flame synthesis of well-defined molybdenum oxide nanocrystals.
AB  - Well-defined faceted inorganic Mo oxide nanocrystals are synthesized in the gas
      phase using a solid-fed-precursor flame synthesis method. The solid crystals have
      rectangular cross-section with characteristic size of 10-20 nm and with lengths
      ranging from 50 nm to a few hundred nanometres. A 1 mm diameter high purity Mo
      probe introduced in the oxygen-rich part of the flame serves as the material
      source. A combination of the strong temperature gradient and varying chemical
      species concentrations within the flame volume provides the ideal conditions for
      the rapid and direct formation of these unique nanocrystals. Oxidation and
      evaporation of MoO3 in the oxygen-rich zone are followed by reduction to MoO2 in
      the lower temperature, more fuel-rich zone. The MoO3 vapours formed are pushed in
      the direction of the gas flow and transformed into mature well-defined convex
      polyhedron nanocrystals bounded with six faces resembling rectangular
      parallelepipeds.

PMID- 19858555
TI  - Magnetization reversal in individual cobalt micro- and nanowires grown by focused
      electron-beam-induced-deposition.
AB  - We systematically study individual micro- and nanometric polycrystalline cobalt
      wires grown by focused-electron-beam-induced-deposition. The deposits were grown
      in a range of aspect ratios varying from 1 up to 26. The minimum lateral
      dimension of the nanowires was 150 nm, for a thickness of 40 nm. Atomic force
      microscopy images show beam-current-dependent profiles, associated with different
      regimes of deposition. The magnetization reversal of individual nanowires is
      studied by means of the spatially resolved magneto-optical Kerr effect. Abrupt
      switching is observed, with a systematic dependence on the wire's dimensions.
      This dependence of the coercive field is understood in magnetostatic terms, and
      agrees well with previous results on cobalt wires grown with different
      techniques. The influence of compositional gradients along the structural profile
      on the magnetic reversal is studied by using micromagnetic simulations. This work
      demonstrates the feasibility of using this technique to fabricate highly pure
      magnetic nanostructures, and highlights the advantages and disadvantages of the
      technique with respect to more conventional ones.

PMID- 19858556
TI  - A role of HNO3 on transparent conducting film with single-walled carbon
      nanotubes.
AB  - There is some controversy regarding the effects of HNO3 on films of single-walled
      carbon nanotubes (SWCNTs). In this study we examined the change in sheet
      resistance of an HNO3-modified SWCNT film after different drying times at 85
      degrees C using various analytical techniques. The shift and suppression in the
      Raman spectra, bleaching of the transition peaks related to van Hove
      singularities and a shift in the original peak in the C 1s XPS spectra provided
      evidence for p-type doping. A decrease in sheet resistance was also observed in
      the SWCNTs films due to the removal of residual N-methylpyrrolidone solvent on
      the surface and bundle of SWCNTs. These results suggest that p-type doping has a
      larger effect on the sheet resistance than the removal of residual N
      methylpyrrolidone by an HNO3 treatment.

PMID- 19858557
TI  - Polymer underlayer assisted dewetting of a top metal nanofilm.
AB  - We demonstrated polymethylmethacrylate (PMMA) polymer underlayer assisted,
      focused-ion-beam (FIB)-induced dewetting of a top Au nanofilm where we found that
      the underlayer played a prominent and, in some cases, a useful role in the
      dewetting of the top layer. For an Au nanofilm deposited on a thick uniform PMMA
      underlayer, where the underlayer is stable and therefore does not dewet,
      irregularly spaced Au nanoparticles (AuNPs) were formed as expected by raster
      scanning of a focused Ga-ion beam. On the other hand, topographically pre
      patterned thin PMMA film provided heterogeneous nucleation sites for both the Au
      top layer and the PMMA underlayer to initiate dewetting at and guidance for
      forming regularly spaced AuNPs with much narrower size distribution at
      significantly lower ion dose levels when compared to the thick, uniform
      underlayer case. We also found that the underlayer assisted dewetting in this
      case relaxes the restriction on pre-pattern periodicity to obtain a single NP per
      pattern period, which is a noteworthy departure from the pre-patterned solid
      substrate case. FIB-induced AuNP areas can have sharp boundaries and can be
      positioned on a selected area of a substrate with high positional accuracy, which
      is important for the implementation of devices in sensing, nano-optics/photonics,
      and optoelectronic applications.

PMID- 19858558
TI  - Using circumacenes to improve organic electronics and molecular electronics:
      design clues.
AB  - Theoretical modeling is used here to ascertain the potential use of circumacenes
      to improve the transport parameters of pi-conjugated materials acting as: (i) the
      layered molecular constituent for organic electronic devices; and (ii) the
      molecular component of gold-molecule-gold nanobridges for molecular electronic
      device use. It is concluded that, to a first approximation, the molecular length
      or, alternatively, the HOMO-LUMO gap (HOMO: highest occupied molecular orbital;
      LUMO: lowest unoccupied molecular orbital) can be used to relate the two
      transport regimes usually found in these two fields, thus serving as a key design
      parameter for guaranteeing good performance of circumanthracene for both regimes.
      It is also clearly established that going beyond this simple relationship
      requires knowledge of the detailed molecule-contact geometry of the molecular
      nanobridge, and how its tremendous impact on the binding strength and the
      conductance prevents blind extrapolation of results obtained for molecular
      nanobridges built by means of different experimental set-ups.

PMID- 19858559
TI  - A novel and simple method to grow beaded nanochains of ZnO with superior
      photocatalytic activity.
AB  - We have demonstrated a novel and simple low-cost method to grow beaded nanochains
      of ZnO using an aqueous chemical growth method. Whatman filter paper (40) is used
      as the template. The filter paper is generally made up of cellulose fibers along
      which the growth of beaded ZnO nanoparticles (NPs) is initiated. When the filter
      paper is burnt at 700 degrees C temperature, the NPs appear as a beaded nanochain
      morphology while those synthesized without the filter paper form lumped
      nanostructures without any regular shape and size. A model has been proposed to
      explain the growth mechanism. A sharp and strong green emission has been observed
      for the template-grown sample in contrast to a broad and less intense hump of the
      without template-grown sample. The beaded nanochains shows 64% photocatalytic
      degradation of methyl orange (MO) under UV irradiation, which is much superior to
      a value of only 22% shown by the lumped sample. Not only can this low-cost simple
      template-based synthesis be applied to grow other nanostructures of similar
      morphology but is also promising for enhancing the properties in the
      multifunctional materials.

PMID- 19858560
TI  - Chemically anisotropic single-crystalline silicon nanotetrahedra.
AB  - We describe a method based on silicon micromachining to machine single
      crystalline silicon nanoparticles bounded by (111) faces in the form of
      tetrahedra. The technology allows the fabrication of tetrahedra in a size range
      from 20 to 1000 nm side length, and gives the possibility to chemically modify
      sites (faces, edges and/or tips) within certain limits. The chemical modification
      is anticipated to facilitate the self-assembly into new supermaterials such as
      photonic crystals in the diamond lattice.

PMID- 19858561
TI  - Self-assembled 3D flower-like Ni2+-Fe3+ layered double hydroxides and their
      calcined products.
AB  - This paper describes a facile solvothermal method to synthesize self-assembled
      three-dimensional (3D) Ni2+-Fe3+ layered double hydroxides (LDHs). Flower-like
      Ni2+-Fe3+ LDHs constructed of thin nanopetals were obtained using ethylene glycol
      (EG) as a chelating reagent and urea as a hydrolysis agent. The reaction
      mechanism and self-assembly process are discussed. After calcinating the as
      prepared LDHs at 450 degrees C in nitrogen gas, porous NiO/NiFe2O4 nanosheets
      were obtained. This work resulted in the development of a simple, cheap, and
      effective route for the fabrication of large area Ni2+-Fe3+ LDHs as well as
      porous NiO/NiFe2O4 nanosheets.

PMID- 19858562
TI  - Electrical control of a laterally ordered InAs/InP quantum dash array.
AB  - We have fabricated an array of closely spaced quantum dashes starting from a
      planar array of self-assembled semiconductor quantum wires. The array is embedded
      in a metallic nanogap which we investigate by micro-photoluminescence as a
      function of a lateral electric field. We demonstrate that the net electric charge
      and emission energy of individual quantum dashes can be modified externally with
      the performance limited by the size inhomogeneity of the self-assembling process.

PMID- 19858563
TI  - Control of channel doping concentration for enhancing the sensitivity of 'top
      down' fabricated Si nanochannel FET biosensors.
AB  - The sensitivity of 'top-down' fabricated Si nanochannel field effect transistor
      (FET) biosensors has been analyzed quantitatively, as a function of the channel
      width and doping concentration. We have fabricated 130-, 150-, and 220 nm-wide Si
      FET channels with 40 nm-thick p-type silicon-on-insulator (SOI) layers doped at 8
      x 10(17) and 2 x 10(18) cm(-3), and characterized their sensitivity in response
      to the variation of surface charges as hydrogen ion sensors within buffer
      solutions of various pH levels. Within the range of channel width and doping
      concentration investigated, the pH sensitivity of Si channels is enhanced much
      more effectively by decreasing the doping concentration than by reducing the
      channel width, which suggests a practical strategy for achieving high sensitivity
      with less effort than to reduce the channel width. Similar behavior has also been
      confirmed in the immunodetection of prostate specific antigen (PSA). Combined
      with excellent reproducibility and uniformity of the channel structure, high
      controllability of the doping concentration can make the 'top-down' fabrication a
      very useful approach for the massive fabrication of high-sensitivity sensor
      platforms in a cost-effective way.

PMID- 19858564
TI  - The situation room: a step by step procedure toward pandemic influenza
      preparedness.
AB  - In the context of the public health surveillance, the situation room might be
      playing an interesting role as a strategy for early alert and follow-up of a
      specific public health event and its determinants. The implementation and proper
      functioning of an influenza situation room monitoring seasonal and pandemic
      influenza or any other public health event could help to mitigate the impact of
      the next pandemic on public health in any country regardless of its level of
      economic development. This paper is aimed to suggest some basic steps for
      implementing an Influenza Situation Room as a strategy of prevention of diseases
      with potential to cause human pandemics and its mitigation if it has already
      occurred.

PMID- 19858565
TI  - Antibiotic Resistance Surveillance and Control in the Mediterranean region:
      report of the ARMed Consensus Conference.
AB  - Antimicrobial resistance has become a global threat to effective health care
      delivery. This is particularly the case within the Mediterranean region, where
      data from recent studies suggests the situation to be particularly acute. A
      better knowledge base, as well as a collaborative effort, is therefore required
      to address this ever increasing challenge to effective patient care. Over its
      four-year period, the Antibiotic Resistance Surveillance and Control in the
      Mediterranean Region (ARMed) project investigated the epidemiology of
      antimicrobial resistance, as well as its contributory factors, in a number of
      countries in the southern and eastern Mediterranean region through the collection
      of comparable and validated data. The project culminated in a consensus
      conference held in Malta in November 2006. The conference provided a forum for
      expert delegates to agree on a number of priority strategic recommendations that
      would be relevant to resistance containment efforts in the region. There was
      general agreement on the need for surveillance and audit to underpin any
      intervention to tackle antimicrobial resistance, both to monitor changing
      epidemiological trends in critical pathogens as well as to identify antibiotic
      consumption practices and effectiveness of prevention and control of health care
      associated infections. In addition, the importance to convey these data to key
      users was also stressed in all workshops, as was better education and training of
      health care workers. The recommendations also made it clear that ownership of the
      problem needs to be improved throughout the region and that resources, both
      financial as well as human, must be allocated by the respective policy makers in
      order to combat it.

PMID- 19858566
TI  - Antimicrobial susceptibility of select respiratory tract pathogens in Dakar,
      Senegal.
AB  - BACKGROUND: Haemophilus influenzae, Moraxella catarrhalis, Streptococcus
      pyogenes, and Streptococcus pneumoniae are the most common causative agents of
      respiratory tract infections (RTIs). The increase in resistance to current
      antibacterial agents highlights the need to monitor the resistance pattern of
      these bacterial pathogens. METHODOLOGY: In this study, we assessed the
      antibacterial susceptibility of these pathogens causing respiratory tract
      infections in Dakar, Senegal, during 2007-2008. A total of 290 bacterial isolates
      (75 H. influenzae, 10 M. catarrhalis, 105 S. pneumoniae, and 100 S. pyogenes)
      were collected. RESULTS AND CONCLUSIONS: All H. influenzae isolates were
      susceptible to amoxicillin/clavulanic acid, ofloxacin, clarithromycin,
      cephalosporins, and macrolides. Overall, 26.7% of H. influenzae isolates were
      completely resistant to ampicillin. Among the M. catarrhalis isolates, 30% were
      resistant to ampicillin. All the isolates of H. influenzae and M. catarrhalis
      that were resistant to ampicillin were beta-lactamase producing strains. Among
      the S. pneumoniae isolates, 33.3% isolates exhibited intermediate susceptibility
      to penicillin G, and one isolate was completely resistant. All five isolates that
      were resistant to erythromycin expressed the M phenotype. S. pyogenes exhibited
      high susceptibility to all other antibiotics, except tetracycline. Our study
      suggests that except for M. catarrhalis, all other bacterial isolates are
      susceptible to cephalosporins, macrolides, and fluroquinolones.

PMID- 19858567
TI  - Relationship of drug resistance to phylogenetic groups of E. coli isolates from
      wound infections.
AB  - BACKGROUND: Drug resistance is a major problem in Escherichia coli isolated from
      surgical wound infections. In this study, we evaluated relationship between
      phylogenicity and drug resistance. METHODOLOGY: A total of 29 multi-drug
      resistant (MDR) E. coli isolates of known drug resistance genes and integron
      profile were selected for the present study. Triplex PCR was conducted for
      phylogenetic classification of these isolates into four established phylogenetic
      groups: A, B1, B2 and D. Statistical analysis was done to determine the
      association of different drug resistance genes and integrons with the
      phylogenetic groups. RESULTS: Most of the isolates (44.8%) belonged to
      phylogenetic group A followed by group B2 and D (24.1% each) and group B1 (6.9%).
      CONCLUSIONS: There is a definitive relationship between drug resistance and
      various phylogenetic groups of E. coli infecting wounds. A shift towards
      phylogenetic group A might be observed with an increasing drug resistance
      profile.

PMID- 19858568
TI  - The in-vitro antimicrobial activity of some medicinal plants against beta-lactam
      resistant bacteria.
AB  - BACKGROUND: In effort to identify novel bacterial agents, this study was
      initiated to evaluate the antimicrobial properties of 17 crude extracts from 12
      medicinal plants against beta-lactam-resistant bacteria. METHODOLOGY: The
      antimicrobial activities of plant extracts were evaluated against clinically
      proved beta-lactam-resistant bacteria (Klebsiella pneumoniae, Klebsiella oxytoca,
      Enterobacter cloacae, Serratia marcescens, Acinetobacter baumannii,
      Staphylococcus aureus and Enterococcus sp.) and reference strains of bacteria
      (Escherichia coli ATCC 35218, Enterobacter aerogenes ATCC 29751, E. aerogenes
      ATCC 13048, Pseudomonas aeruginosa ATCC 27853 and Enterococcus hirae ATCC 9790)
      by using disc-diffusion and agar-dilution assays. RESULTS: The crude plant
      extracts demonstrated broad spectrum activity against all bacteria tested with
      inhibition zones in the range of 8-30 mm. The minimal inhibitory concentration
      (MIC) values of different plant extracts against the tested bacteria were found
      to range from <or= 0.3 to >or= 10 mg ml(-1). The most active plant extracts were
      from Dortenia picta and Bridelia micrantha (MIC: 1.25-10 mg ml(-1)) on beta
      lactam-resistant Gram-negative bacilli and the extracts from B. micrantha,
      Mallotus oppositifolius, Garcinia lucida, Garcinia. kola, Campylospermum
      densiflorum (leaves) and C. zenkeri (root) on beta-lactam-resistant Gram-positive
      cocci (MIC: <or= 0.3-5 mg ml(-1)). CONCLUSION: Of the 17 plant extracts studied,
      seven showed good antimicrobial activity against the tested bacteria. The stem
      bark of B. micrantha and the leaves of D. picta were most active towards beta
      lactamase producing Gram-negative bacilli. This study shows that medicinal plants
      could be sources of compounds which can be used to fight against beta-lactam
      resistant bacteria.

PMID- 19858569
TI  - Methicillin resistant Staphylococcus aureus: prevalence and antibiogram in a
      tertiary care hospital in western Nepal.
AB  - BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is a major cause
      of nosocomial and community infections. Its prevalence varies with country and
      with hospitals within a country. The current study estimates the prevalence of
      MRSA strains and investigates their antibiogram in western Nepal. METHODOLOGY: A
      total of 162 S. aureus strains were isolated from various clinical specimens, and
      antibiotic susceptibility tests were performed using disc diffusion, growth on
      oxacillin screen agar, and oxacillin minimum inhibitory concentration (MIC).
      RESULTS: One hundred and twelve (69.1%) strains were found to be MRSA, of which
      37 (33.1%) were community acquired and 75 (66.9%) were hospital acquired. Of 112
      MRSA strains, 45 (40.1%) were multi-drug resistant. All MRSA strains were found
      resistant to penicillin, and 91.9%, 87.4%, 77%, and 55.5% were resistant to
      amoxicillin, ampicillin, trimethoprim/sulfamethoxazole, and cephalexin,
      respectively. However, low resistance was observed with amikacin (19%),
      ciprofloxacin (26.5%), and norfloxacin (30.6%). All strains were sensitive to
      vancomycin. CONCLUSION: The reported rate of MRSA prevalence is alarming. Given
      the ability of MRSA to spread from person to person, it is necessary to adhere to
      rational use of antibiotics and to raise awareness among the concerned
      communities and tourists who visit this area.

PMID- 19858570
TI  - Phenotypic and genotypic analysis of clinical isolates Salmonella serovar
      Typhimurium in western Kenya.
AB  - BACKGROUND: Salmonella spp. are recognized as some of the most common causes of
      enteritis worldwide. This study aimed to identify clinically isolated S.
      Typhimurium in western Kenya and to assess antimicrobial resistance profiles and
      strain inter-relatedness. METHODS: The study was performed in rural Maseno,
      Nyanza province in Kenya, between February 2004 and June 2005. Sixty-three
      patients with diarrhoea and fever were recruited. S. Typhimurium isolates were
      confirmed using serotyping, biochemical testing, and 16S rRNA sequencing.
      Susceptibility to 20 antimicrobials was determined and specific resistance genes
      were identified by polymerase chain reaction (PCR). Strain diversity was further
      analyzed using pulsed-field gel electrophoresis (PFGE), fluorescence amplified
      fragment length polymorphism (fAFLP), and multi-locus-variable-number-tandem
      regions (MLVNTR). RESULTS: Twenty S. Typhimurium strains were isolated in the
      course of the study and their identity was confirmed by 16S rRNA gene sequencing.
      All 20 S. Typhimurium strains were resistant to ampicillin, streptomycin and
      sulfamethoxazole; ciprofloxacin resistance and phage DT104 were not detected.
      PFGE, plasmid profiling, and analysis of selected VNTR loci revealed further
      heterogeneity among the strains in the study. CONCLUSION: S. Typhimurium was
      commonly isolated from patients with diarrhoea and fever in Maseno. Considerable
      phenotypic and genotypic diversity was observed among isolates, suggesting that
      strains belonging to multiple lineages are responsible for disease in the study
      region. Multiple resistance was common and mediated by a variety of resistance
      genes but not by phage DT104.

PMID- 19858571
TI  - Characterization of Salmonella Enteritidis isolated from foods and patients in
      northern Morocco.
AB  - OBJECTIVES: This study aimed to investigate Salmonella Enteritidis strains
      isolated from human and food sources in the north of Morocco by means of
      phenotypic and genotypic methods. METHODOLOGY: Fifteen isolates from humans and
      food were submitted to phage typing, XbaI-macrorestriction (pulsed field gel
      electrophoresis [PFGE]), enterobacterial repetitive intergenic consensus (ERIC
      PCR), antimicrobial susceptibility testing, and PCR assay targeting the spvR and
      invA genes. RESULTS: Six fingerprinting profiles were obtained with the ERIC-PCR
      method, four with PFGE profiling, five with antimicrobial resistance, three with
      phage typing, and only one with plasmid profiling. spvR gene was detected in six
      strains, which did not harbour plasmids of 90 kb. CONCLUSIONS: The conclusions of
      this study are drawn from a limited number of isolates. It would be desirable to
      investigate a greater and more diverse population of Salmonella isolates. S.
      Enteritidis was genotyped and showed four different patterns by PFGE and six by
      ERIC-PCR. Accordingly, high genetic similarity and limited genetic diversity were
      found for these strains from north of Morocco.

PMID- 19858572
TI  - Ventilator-associated nosocomial pneumonia in intensive care units in Malaysia.
AB  - BACKGROUND: The outcome indicator of nosocomial infection (NI) in the intensive
      care unit (ICU) is used to benchmark the quality of patient care in Malaysia. We
      conducted a three-year prospective study on the incidences of ventilator
      associated pneumonia (VAP), risk factors, and patterns of the microorganisms
      isolated in three ICUs. METHODOLOGY: A follow-up in prospective cohort
      surveillance was conducted on patients admitted to an adult medical-surgical ICU
      of a university hospital and two governmental hospitals in Malaysia from October
      2003 to December 2006. VAP was detected using CDC criteria which included
      clinical manifestation and confirmed endotracheal secretion culture results.
      RESULTS: In total, 215 patients (2,306 patient-days) were enrolled into the
      study. The incidence of ICU-acquired device-related NI was 29.3 % (n = 63). The
      device-related VAP infection rate was 27.0 % (n = 58), with a mechanical
      ventilator utilization rate of 88.7%. The death rate due to all ICU-acquired NI
      including sepsis was 6.5%. The most common causative pathogen was Klebsiella
      pneumoniae (n = 27). Multivariate analysis using Cox regression showed that the
      risk factors identified were aspiration pneumonia (HR = 4.09; 95% CI = 1.24,
      13.51; P = 0.021), cancer (HR = 2.51; 95% CI = 1.27, 4.97; P = 0.008),
      leucocytosis (HR=3.43; 95% CI= 1.60, 7.37; P=0.002) and duration of mechanical
      ventilation (HR=1.04; 95% CI = 1.00, 1.08; P = 0.030). Age, gender and race were
      not identified as risk factors in the multivariable analysis performed.
      CONCLUSION: The incidence of VAP was comparable to that found in the National
      Nosocomial Infection Surveillance (NNIS) System report of June 1998. The
      incidence of VAP was considered high for the three hospitals studied.

PMID- 19858573
TI  - A dengue transmission model in Thailand considering sequential infections with
      all four serotypes.
AB  - BACKGROUND: Dengue fever/dengue haemorrhagic fever is prevalent in Thailand,
      where all serotypes are found and the dominant serotype has changed irregularly.
      Although almost all primary infections present with slight symptoms or are
      asymptomatic, little is known about the infectiousness of dengue fever.
      METHODOLOGY: A mathematical model of the transmission for dengue virus was
      constructed covering the possibility of sequential infections with all four
      different serotypes. The model was combined with the seasonal population dynamics
      of Aedes aegypti, the principal vectors of dengue virus in Thailand. The
      contributions of inapparent cases in the transmission to mosquito vectors and
      antibody-dependent enhancement were incorporated into the model. Moreover, the
      hypothesis of an "unnatural" infection route was examined, where a person
      acquires immunity by infection during a cross-immunity period, through model
      simulations. RESULTS: A comparative study on the transmission probabilities of
      inapparent cases to mosquito vectors showed that the prevalence of dengue
      infection could be immediately stamped out after a severe outbreak if inapparent
      cases had no infectiousness. The simulation under an "unnatural" infection route
      assumption resulted of yearly changes in the dominant serotype and sharp,
      irregular variations in outbreaks. CONCLUSION: The supposition that inapparent
      cases had no infectiousness was not in accord with the actual situation in
      Thailand. Furthermore, the simulation result supported the "unnatural" infection
      route as having an influence on epidemics of dengue.

PMID- 19858574
TI  - The aetiology of acute community acquired bacterial meningitis in children and
      adults in Maputo, Mozambique.
AB  - BACKGROUND: Community-acquired acute bacterial meningitis is a life-threatening
      infection and many outbreaks have been reported all around the world.
      METHODOLOGY: We analysed 330 cerebrospinal fluid (CSF) samples received over a
      period of eight months from patients older than one month. Microscopy, cultures,
      identification, and antigen detection were performed for the positive samples.
      RESULTS: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus
      influenzae type b were isolated in 5.4%, 4.8%, and 3.6% of CSF samples
      respectively. CONCLUSIONS: Our findings indicate that N. meningitidis is the most
      common cause of acute bacterial meningitis in Mozambique and that H. influenzae
      type b was isolated only from children aged younger than six years. This is the
      first study to provide data on the aetiological agents of acute bacterial
      meningitis in children and adults in Mozambique.

PMID- 19858575
TI  - Household fish preparation hygiene and cholera transmission in Monrovia, Liberia.
AB  - BACKGROUND: In the 1980s Vibrio cholerae was found to be an autochthonous
      resident of aquatic environments. As result, ingestion of undercooked,
      contaminated fish has been associated with cholera transmission. An alternative
      mechanism of transmission associated with fish was hypothesised by Schurmann et
      al. in 2002. He described a cholera case that was more likely to have been
      infected by contamination on the patient's hands rather than by ingestion of
      contaminated fish. METHODOLOGY: With fish being the main diet in Liberia, we
      decided to examine fish samples and preparation techniques in Monrovia. Excreta
      of 15 fish, caught in the estuarine waters of Monrovia, were analysed for V.
      cholerae. In addition, fish preparation methods were observed in 30 households.
      RESULTS: Two fish samples were found positive. Observations revealed that hygiene
      measures during the gutting process of fish were limited; although hands were
      usually rinsed, in all cases soap was not used. Furthermore, contaminated water
      was frequently reused during food preparation. CONCLUSIONS: Since the cooking
      process of fish (and thus elimination of bacteria) in Monrovia usually consists
      of both frying and boiling, it seems plausible that in this context, the
      hypothesis by Schurmann et al. could be applicable. Further research is necessary
      to confirm this association, which could be a starting point for more context
      specific health education campaigns addressing food preparation hygiene as risk
      factor for cholera.

PMID- 19858576
TI  - Primary echinococcal cyst in the thyroid gland: a case report from Iran.
AB  - Hydatid disease is prevalent in most sheep-raising countries in Asia , Australia
      , East, and Southern Europe. Hydatid disease caused by Echinococcus granulosus is
      often manifested by a slow growing cyst mass. Hydatid cysts may be found in
      almost every parts of the body. However the lungs and liver are the most involved
      locations. Due to the vital cycle of the parasite the thyroid gland is an
      uncommon site of infection even in the countries where the disease is endemic.
      However, hydatic origin was suspected in only 50% of patients preoperatively and
      immunologic test had 33% false positive rate. Although hydatid cyst was
      considered intra-operatively and confirmed by a frozen section histology. This
      study is to report a case of primary hydatid disease of the thyroid.

PMID- 19858577
TI  - Molecular identification of T. brucei s.l. in tsetse flies after long-term
      permanence in field traps.
AB  - BACKGROUND: Tsetse flies (Glossina spp.) are responsible for the transmission of
      trypanosomes, agents of animal and Human African Trypanosomiasis (HAT). These
      diseases are associated with considerable animal and human economical loss,
      morbidity and mortality. The correct identification of trypanosomes species
      infecting tsetse flies is crucial for adequate control measures. Identification
      presently requires technically difficult, cumbersome and expensive on-site fly
      dissection. To obviate this difficulty we explored the possibility of correctly
      identifying trypanosomes in tsetse collected, under field conditions, only for
      number determination. METHODOLOGY: Tsetse flies, that remained exposed for weeks
      in field traps in the Vista Alegre HAT focus in Angola, were obtained. The flies
      were not dissected on site and were stored at room temperature for months. DNA
      extraction using the whole tsetse bodies and PCR analysis were performed in 73
      randomly chosen flies. RESULTS: Despite the extensive degradation of the tsetse,
      DNA extraction was conducted successfully in 62 out of the 73 flies. PCR analysis
      detected the presence of T. brucei s.l DNA in 3.2 % of the tsetse. CONCLUSIONS:
      This approach could be cost-effective and suitable for vector related HAT control
      activities in the context of countries where entomological trained personnel is
      missing and financial resources are limited.

PMID- 19858578
TI  - An evidence-based update on hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a disturbance of the central nervous system (CNS)
      function secondary to porto-systemic shunting. It usually occurs in the setting
      of advanced liver cirrhosis or acute fulminant hepatic failure. An extensive
      Medline search was undertaken and all relevant papers found were critically
      examined. Special emphasis was paid to clinical trials and meta-analyses. All
      guidelines and conference proceedings related to hepatic encephalopathy were also
      examined. HE presents with a spectrum of neuropsychiatric manifestations that may
      be quite subtle (minimal HE) or overt, ranging from disturbance of the sleep
      pattern to deep hepatic coma. Most patients with HE may be diagnosed on clinical
      grounds only after excluding other causes of neurological disease, but a wide
      variety of neuropsychological, neurophysiological, and neuroradiological tests
      may be utilized. The first step in the management of patients with HE should be
      supportive care. Following that, a significant effort must be exerted to find and
      correct possible exacerbating factors which may include: renal impairment,
      infection, constipation, drugs, gastrointestinal bleeding and other factors.
      Medications used to treat patients with encephalopathy aim to reduce toxin
      production, increase toxin elimination, and protect the brain from the harmful
      effects of these toxins. A critical analysis of the evidence concerning most of
      the available management modalities is presented. Ultimately, all patients with
      HE must be considered for liver transplantation. It is concluded that early
      recognition, positive diagnosis, and a multi-target management plan constitutes
      appropriate management of patients with HE.

PMID- 19858580
TI  - Helicobacter pylori seropositivity in children with chronic disease in Jeddah,
      Saudi Arabia.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is an important pathogen in
      gastrointestinal disorders. Seroprevalence among asymptomatic and chronically
      diseased children in Jeddah, Saudi Arabia was determined to gain insight into its
      prevalence. METHODS: Serum samples obtained from 1432 children; 543 asymptomatic
      and 889 chronically diseased children (diabetes, chronic asthma, chronic
      hemolytic anemia, neurological impairment and Down's syndrome); were tested by
      ELIZA for H. pylori IgG antibodies. Demographic data obtained including
      nationality, gender, age and disease status. RESULTS: One hundred and twenty
      eight (23.6%) of 543 asympatomatic children were seropositive with no significant
      difference in seroprevalence of infection between Saudi and non-Saudi (p<0.09)
      and between boys and girls (p<0.67), but significant rise was notice with
      increasing age (p<0.001). An increase in risk of H. pylori among chronically
      diseased children was observed (diabetes: 34.4%, chronic asthma 20.4%, chronic
      hemolytic anemia: 31.7%, neurological impairment: 32.1%, and Down's syndrome:
      29.2%) which increased significantly in chronic anemia and neurological
      impairment (p<0.01 and p<0.05) compared to controls. The prevalence did not
      differ according to nationality and gender but significantly increased with age
      in chronic asthma, chronic anemia and neurological impairment (p<0.01 for all)
      and also increased significantly with duration of illness, number of blood
      transfusions, number of hospital admission and mode of feeding. CONCLUSION:
      Infection with H. pylori seems to occur early in life and its prevalence
      increased with age in Jeddah, Saudi Arabia. The risk of H. pylori infection was
      significantly increased within children suffering from chronic hemolytic anemia;
      neurological impairment compared to controls and was significantly related to
      severity of the chronic disease.

PMID- 19858579
TI  - Importance of Helicobacter pylori eradcation for maintenance of remission of drug
      associated peptic ulcer disease.
AB  - BACKGROUND: The role of Helicobacter pylori (H. pylori) eradication in non
      steroidal anti inflammatory drug (NSAID) users with peptic ulcer disease is
      controversial especially in countries with a high prevalence of the infection.
      Furthermore the value of low dose omeprazole for maintenance of remission is not
      yet known. PATIENTS AND METHODS: 138 symptomatic out-patients receiving
      continuous COX 1 NSAID therapy, were treated with omeprazole 40 mg/day upon
      endoscopic confirmation of gastro-duodenal ulceration or erosions while those
      infected with H. pylori received in addition clarithromycin 500 mg and
      amoxycillin 1000 mg twice daily during the first week of treatment. After
      endoscopic confirmation of healing at the end of week 5, the patients were
      randomized to receive omeprazole 10 mg (n=50) or 20 mg once daily (n=66) and
      endoscopy repeated after 20 weeks. RESULTS: The overall healing rate (per
      protocol) at five weeks (116/128) was 90.6% while in 85.5% (65/76) eradication
      was successful. The healing rate for the H. pylori eradicated patients (58/65)
      was 89.2%. For those who failed eradication (8/11) it was 72.7% (NS), while for
      patients not infected with H. pylori at entry to the study (50/52) it was 96.2%
      (NS). An intention to treat analysis showed that after 20 weeks of omeprazole
      prophylaxis with the 10mg dose 86% (43/50) had maintained healing while for the
      20mg dose a similar figure was observed (87.9; 58/66). Only three patients in the
      two groups (pp) had persistent H. pylori infection, all of whom relapsed. No
      patients discontinued treatment because of adverse effects of the drugs.
      CONCLUSION: H. pylori eradication was not associated with impaired ulcer healing
      in a Middle Eastern population with symptomatic NSAID induced gastro/duodenal
      lesions, when a high healing dose of omeprazole (40 mg) was used. After
      eradication, omeprazole 10 or 20 mg per day were highly and equally effective for
      maintenance of gastroduodenal mucosal integrity during continued NSAID use. H.
      pylori should be eradicated from symptomatic Middle Eastern NSAID users with
      peptic ulcer disease.

PMID- 19858581
TI  - The impact of elective diagnostic laparoscopy in chronic abominal disorders.
AB  - OBJECTIVES: Diagnostic laparoscopy has become an integral part of general
      surgical procedures with the recent advancements in laparoscopic technology.
      Since surgeons are more oriented in viewing and dissection of different intra
      abdominal areas and are proficient in the definitive management of complications
      in the procedures, diagnostic laparoscopy may be better off in the hands of
      surgeons. Laparoscopy has proved to be an important tool in final minimally
      invasive exploration for selected medical patients with chronic abdominal
      disorders, the diagnosis of which remains uncertain despite employing the
      requisite laboratory and non-invasive imaging investigations. This retrospective
      study was done to evaluate the accuracy of elective diagnostic laparoscopy in
      patients with chronic abdominal disorders and its impact on the management of
      these patients. METHODS: The records of 35 patients, admitted to Riyadh Medical
      Complex with chronic abdominal disorders and referred to the author by physicians
      for elective diagnostic laparoscopy from 1999 through 2004, were evaluated for
      the accuracy and impact of this procedure in the further management of these
      patients. All 35 patients were investigated by the referring physician.
      Investigations included hematology, biochemistry, radiology, ascitic fluid
      analysis, endoscopic and imaging studies and the Mantoux test. These
      investigations suggested abdominal tuberculosis in 22 patients and intra
      abdominal malignancy in 13 patients. They were referred for elective diagnostic
      laparoscopy and tissue biopsy. RESULTS: Diagnostic laparoscopy confirmed the
      diagnosis in all patients suspected of malignancy. In patients with suspected
      abdominal tuberculosis, the laparoscopic diagnosis and biopsy revealed
      tuberculosis (16 patients), liver cirrhosis (2 patients), Crohn's disease (1
      patient), and metastatic carcinoma of terminal ileum (1 patient). In 2 patients
      the procedure did not reveal any specific pathology. The accuracy of the
      preoperative investigations for those suspected to have abdominal tuberculosis
      was 71 %. There was 100% impact of diagnostic laparoscopy on the management of
      all 35 patients since, in the 2 patients with negative laparoscopy, at least
      tuberculosis and malignancy were excluded. CONCLUSION: Diagnostic laparoscopy in
      the hands of surgeons proved to have an impact as an investigation technique,
      where the diagnosis remained uncertain after the laboratory and non-invasive
      investigations, of selected medical patients with chronic abdominal disorders. It
      is a minimally invasive procedure which has a high percentage of accuracy in
      diagnosis and impact in the further management of selected patients.

PMID- 19858582
TI  - Endoscopic duodenal biopsy in children.
AB  - BACKGROUND: Biopsy of the small bowel is frequently obtained by endoscopic
      forceps instead of the classical suction capsule, yet reports from developing
      countries are scarce. AIM OF THE STUDY: to report our experience on the
      diagnostic value of this procedure in our community. PATIENTS AND METHODS: A
      retrospective analysis of all endoscopic duodenal biopsies (EDB), performed on
      all patients below 18 years of age. Data retrieved from the records included age,
      gender, nationality, indication for biopsy, the endoscopic findings, and the
      results of histopathology. RESULTS: From 1993 to 2002, 241 endoscopic biopsies
      were performed on 241 consecutive children. Most of the children (96%) were Saudi
      nationals, the age range between six weeks to 18 years, and male to female ratio
      was 0.7:1. All of the biopsy material was adequate for routine histopathology.
      The commonest indications for biopsy were short stature and chronic diarrhea in
      116/241 (48%) and 102/241 (43%) of the children respectively. Refractory rickets
      accounted for 11/241 (5%) of the indications. The prevalence of villous atrophy
      was highest in children presenting with chronic diarrhea (40%), compared to short
      stature (22%). Other less common, but important findings were villous atrophy in
      three unusual conditions (one refractory rickets, one unexplained anemia, and one
      polyendocrinopathy), two cases of intestinal Giardia lamblia infestation, three
      cases of intestinal lymphangiectasis and one case of Mycobacterium avium
      intracellulare. Unexpected endoscopic findings were documented in 34/241 (14%) of
      the children. CONCLUSIONS: Endoscopic duodenal biopsy is adequate not only for
      the diagnosis of villous atrophy, but also for the detection of other
      gastroenteropathies. Accordingly, when expertise and equipment are available, EDB
      should be the procedure of choice not only in industrialized but also in
      developing countries.

PMID- 19858583
TI  - Allgrove syndrome: reports of cases and literature review.
AB  - We report a series of three mentally-retarded patients who presented with
      dysphagia, cough and recurrent pulmonary infection, adrenal insufficiency and
      alacrimia. Investigations included ultrasonography and CT scan of the abdomen, in
      addition to barium swallow, esophageal manometry and esophagoscopy confirming the
      diagnosis of achalasia. Glucocorticoid therapy was prescribed whereas alacrimia
      was managed by lubricants. In two of our patients dysphagia responded to
      dilatation while the third required cardiomyotomy.

PMID- 19858584
TI  - Endocannabinoids and non-alcoholic steatohepatitis.
AB  - Non alcoholic steatohepatitis (NASH) has gained a lot of attention recently due
      to the increased prevalence of diabetes, obesity, and hyperlipedemia. The
      endogenous compounds, endocannabinoids (ECBs), bind to the same receptors as
      tetrahydrocannabinol, the active component in marijuana and hashish. Recently,
      two G-proteins coupled, and specific receptors, to cannabinoids, CB1 & CB2, which
      act via adenylate cyclase and calcium channels, were described. In this brief
      review, we shed light on the possible relation between NASH and these proteins.
      It has been hypothesized that ECBs regulate peripheral lipogenesis. Some studies
      suggest that in CB1-deficient mice there is complete resistance to the
      development of diet-induced hepatic steatosis, while wild-type mice showed
      remarkable hepatic steatosis after 3 and 14 weeks of high-fat diet. Based on
      these results and others, the hepatic ECB system may be a target for the
      treatment of NASH. The CB1 antagonist, Rimonabant, will shortly be approved for
      the treatment of obesity and may thus reduce the necessity for bariatric surgery.

PMID- 19858585
TI  - Mycophenolate mofetil (CellCept) in patients with autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver of
      unknown cause. Typically, immune suppressive therapy is used initially for
      treatment, either in the form of steroids or Azathioprime. In a small proportion
      of patients, steroids resistance or steroid intolerance develops. When patients
      are unresponsive to steroids, or develop severe significant side effects to their
      use, alternative treatments must be used. Mycophenolate mofetil (Cellcept) is a
      potent immune suppressive medication that is used in a wide variety of autoimmune
      diseases as well as post solid organ transplantation. Data is emerging to suggest
      that this medication may be used in selected patients with steroid resistance or
      steroid intolerance. This data is summarized in this review.

PMID- 19858586
TI  - Post liver transplantation complications.

PMID- 19858587
TI  - Neuropsychiatric side-effects of interferon alfa therapy for hepatitis C and
      their management: a review.
AB  - BACKGROUND: Interferon-Alfa (IFN-alpha) has been the mainstay of treatment for
      chronic hepatitis C. It has the potential to alter the course of chronic
      hepatitis C and prevent complications. AIMS: This review summarizes current
      knowledge about the presentation, mechanism, course, and treatment of
      neuropsychiatric problems associated with interferon alfa (IFN-alpha) treatment.
      METHODS: Studies were identified by computerized searches, and further references
      were obtained from bibliographies of the reviewed articles. RESULTS:
      Neuropsychiatric symptoms frequently occur in hepatitis C patients treated with
      IFN-Alfa. These side effects are troublesome and frequently account for dose
      reduction or treatment discontinuation. Sometimes, they could be serious and
      possibly life threatening. Frequent psychiatric evaluations of high risk
      individuals and, when required, early administration of antidepressants could
      possibly help to avoid the development of an impending depression or reduce its
      severity and duration and thus increase adherence to treatment. CONCLUSION:
      Greater cooperation between psychiatrists and hepatologists would mean less risk
      of having the serious side effects with more importance needs to be given to the
      identification of patients at risk.

PMID- 19858588
TI  - The role of leptin in non-alcoholic fatty liver disease.
AB  - BACKGROUND: The role of steatosis in the pathogenesis of chronic liver disease
      (CLD) is now believed to form part of a continuum in non-alcoholic fatty liver
      disease (NAFLD). One of the unconventional areas in which leptin is now receiving
      great attention is liver diseases. Several published studies indicate that
      circulating leptin is increased in patients with cirrhosis, chronic HCV, and non
      alcoholic steatohepatitis (NASH). AIMS: the present study aims to assess serum
      leptin levels in patients with NAFLD with and without HCV infection, and to
      correlate it with the biochemical markers and histopathology of liver diseases.
      PATIENTS AND METHODS: the present study included 67 Saudi subjects divided into 3
      age and sex-matched groups. Group A: 22 patients with DM (8 males and 14 females,
      mean age 44 +/- 12.9 years). Group B: 20 patients with chronic HCV infection (7
      males and 13 females, mean age 48.9 +/- 14.1 years). Group C: 25 control healthy
      volunteers (15 males and 10 females, mean age 40.7 +/- 12.6 years). Serum leptin,
      C-peptide, and insulin levels were measured by radioimmunoassay. Liver biopsy was
      done for the HCV group only. RESULTS: Patients with chronic HCV infection had
      significantly lower mean +/- SD serum leptin levels (25.6 +/- 37.2 ng/mL)
      compared with the diabetic and control groups, 55.7 +/- 59.0 and 81.8 +/- 41.7
      ng/mL (p = 0.002 and p = 0.046 respectively). However, in the HCV group, leptin
      levels did not differ significantly as regard steatosis grade, and fibrosis
      stage. Steatosis in the HCV group patients correlated with the body mass index
      and hyperglycemia, but not with leptin levels. Serum leptin correlated positively
      with serum insulin and C-peptide levels in both the HCV and diabetic groups, but
      not in the control group). CONCLUSION: Serum leptin can't be used as a non
      invasive marker for the predication of steatosis and fibrosis in patients with
      NAFLD.

PMID- 19858589
TI  - Clinical presentation, response to therapy, and predictors of fibrosis in
      patients with autoimmune hepatitis in Saudi Arabia.
AB  - BACKGROUND: Autoimmune hepatitis (AIH) is a relapsing inflammatory disease of the
      liver of unknown cause. Little is known about AIH in Saudi Arabia. OBJECTIVES:
      Our aim is to 1) identify the special clinical or histological features in our
      patients, 2) describe the initial response to immunosuppressive therapy and long
      term relapse, 3) identify clinical and laboratory predictors of response to
      therapy, and 4) examine the utility of laboratory markers (platelet count,
      AST/ALT ratio, and the AST to platelet ratio index (APRI score) in predicting the
      presence of advanced fibrosis. METHODS: Patients were identified using a computer
      database. Patients responding to initial therapy were compared with patients who
      did not respond in terms of laboratory and histology parameters. The utility of
      three fibrosis markers/models were then examined. RESULTS: Thirty-nine patients
      with AIH were included in this analysis. The mean age was 45.4; 65% of patients
      were females. Mean ALT at presentation was 268 U/L and AST was 277 U/ L. GGT
      level was found to be the only statistically significant laboratory or
      histopathological parameter difference between responders and non-responders.
      Platelet count and AST/ALT ratio were found to be the best predictors of advanced
      fibrosis. CONCLUSION: In Saudi patients with AIH, we found that the GGT level at
      presentation may serve as a useful predictor for response to therapy. Platelet
      count and AST/ALT ratio may be used to predict advanced fibrosis.

PMID- 19858591
TI  - Colorectal carcinoma: clinico-pathological pattern and outcome of surgical
      management.
AB  - OBJECTIVE: To report the pattern of presentation of colorectal carcinoma and the
      outcome of surgical therapy in a tertiary care hospital in Riyadh Saudi Arabia.
      METHODS: The case reports of all patients diagnosed to have colorectal cancer
      were retrospectively examined for: age, sex, symptoms and clinical findings, site
      of primary tumour and extent of metastases, operative management, histopathology
      results and the outcome of surgical therapy. RESULTS: There were forty-three (33
      male, 10 female) patients, with a mean age of 42.7 years (range, 23-79 years).
      Sixteen (37.2%) cases presented with rectal bleeding, ten (23.2%) with abdominal
      pain, eight (18.5%) had altered bowel habits whereas anaemia was found to be the
      most frequent clinical result reported in twenty (46.4%) patients. Right side
      tumour was encountered in twenty-one (48.8%) cases, left side tumour in twelve
      (27.9%) and anorectal cancer in ten (23.2%).For these lesions, thirty (69.7%)
      curative and thirteen (30.3%) palliative procedures were undertaken. All patients
      were reported to have adenocarcinomas: six (13.9%) patients had Dukes Stage A,
      eight (18.6%) Dukes B, twenty (46.1%) Dukes C and nine (20.9%) Dukes D. There
      were two post operative deaths, and four (9.3%) patients died due to tumour
      dissemination and cachexia, while twenty nine (67.4%) subjects had disease free
      survival. CONCLUSION: There is a substantial proximal shift of the colorectal
      carcinoma with more advanced lesions at the time of presentation. Surgical
      resection should be the mainstay treatment with potentially curable tumours.

PMID- 19858590
TI  - Hypertensive lower esophageal sphincter (HLES): prevalence,symptoms genesis and
      effect of pneumatic balloon dilatation.
AB  - BACKGROUND:  SUMMARY AND BACKGROUND DATA: The Hypertensive lower esophageal
      sphincter (HLES) is an unusual primary motor disorder of the esophagus. The
      significance of this motility disorder is still questionable. OBJECTIVE: The
      objectives were: (a) identification of the prevalence of HLES in these patients,
      (b) identification of the common presenting symptoms of HLES, (c) study of the
      correlation of the symptoms with LESP and (d) study of the effectiveness of
      pneumatic balloon dilation in cases that fail to respond to medical treatment.
      METHODS: A retrospective study that includes four thousand one hundred and
      seventy patients, who were subjected to esophageal manometry in the period from
      January 1994 to December 2003, among whom sixty-six patients with HLES (LESP> 40
      mmHg) were found. In addition to manometry, upper endoscopy was done to forty
      nine patients, upper GI barium studies to thirty-eight patients and esophageal pH
      metry to sixteen patients. RESULTS: showed that most of our patients were
      females (45 females and 21 males), with a mean age of 36.6 +/- 14 years. Patients
      with dysphagia (57.5%) had the highest LESP (52.1 +/- 21, mmHg) while patients
      with chest pain (47%) had the highest distal esophageal contraction amplitude
      (153.9 +/- 93.2 mmHg). Endoscopy showed varying degrees of esophagitis in 17
      patients (34%). Barium studies showed corkscrew esophagus in seven patients
      (18.4%) and dilated esophagus in nine patients (23.7%). LESP was highest in
      patients with dilated esophagus (57.5 +/- 33.4 mmHg). All our patients were
      subjected to medical treatment, of which twelve patients underwent pneumatic
      dilation with successfully reduced LESP and symptoms relief in 91% of patients.
      CONCLUSIONS: It was concluded that the prevalence of HLES is around 1.6, in which
      dysphagia and chest pain are the usual presenting symptom, and that pneumatic
      balloon dilatation is very effective when properly applied. It will probably
      occupy the same position it has in achalasia.

PMID- 19858592
TI  - Non surgical management of the colonoscopic perforation: report of a case.

PMID- 19858593
TI  - Video capsule endoscopy and the hidden gastrointestinal diseases.
AB  - Video capsule endoscopy (VCE) has recently been introduced to fill the gap
      between examinations of the upper and lower gastrointestinal tract, mainly to
      examine the small bowel (SB) for sources of obscure bleeding in addition to many
      other indications. VCE represents a minute endoscope, embedded in a swallowable
      capsule that is propelled by peristalsis and achieves the journey to the right
      colon in 5-8 hours. Images captured by the capsule are recorded on a hard drive
      attached to the patient's belt. Many studies have recently shown that the
      diagnostic yield of VCE is superior to that of push enteroscopy. This mini-review
      contains information on the technical aspects, indications, safety and tolerance
      of VCE. It is well known that radiological investigations of the small bowel (SB)
      have a limited diagnostic yield, are relatively invasive, and often lead to late
      discovery of diseases, especially malignancy and profuse bleeding, at a worse
      stage. Also, push enteroscopy is limited by the depth of the insertion of the
      instrument to the proximal jejunum and, in the retrograde, to the last 50-80 cm
      of the terminal ileum, with an ability to visualize the entire SB only in 10-70%
      of cases. Introduction of video capsule endoscopy (VCE) is therefore regarded a
      significant advance in investigating intestinal diseases, and closes the gap in
      evaluating the SB, "the black box" of endoscopy. This mini-review describes the
      current indications of VCE and the prerequisites for accurate examination, and
      briefly discusses its tolerance and safety.

PMID- 19858594
TI  - The liver in tuberculous peritonitis.
AB  - Tuberculous peritonitis is a common form of abdominal tuberculosis and is
      frequently associated with liver disease. Diagnosis of this disease presents a
      diagnostic dilemma and the presence of liver cirrhosis further confounds the
      clinical picture. Moreover, the co-existence of these two diseases casts doubt on
      the validity of various diagnostic tests available. The interpretation of tests
      of ascitic fluid analysis becomes questionable despite the fact that peritoneal
      tuberculosis and liver disease cause ascites to develop through separate
      mechanisms. In addition, the treatment of tuberculosis mandates a better
      understanding of the co-existent disease in view of the potential hepatotoxicity
      of anti-tuberculous medication. This review aims to address the prevalence of
      coexistent liver disease in patients with tuberculous peritonitis, the diagnostic
      difficulties posed by such and the various treatment approaches to be adopted.

PMID- 19858595
TI  - Multiple irregular liver lesions.

PMID- 19858596
TI  - The role of ultrasonography in portal hypertension.
AB  - Portal hypertension is a commonly encountered clinical condition with multiple
      causes and several squeal. Ultrasound is an accurate non-invasive means of
      assessing its aetiology, severity and complications. I will review the role of
      ultrasonography in portal hypertension. The ultrasonic features that help
      identify its aetiology will be discussed as will the criteria that allow an
      assessment of disease severity and its complications.

PMID- 19858597
TI  - Gastrointestinal Non-Hodgkin's lymphoma: a clinico-pathological study.
AB  - OBJECTIVES: The aim of this study is to determine the clinico-pathological
      features of primary gastrointestinal non-Hodgkin's lymphoma (GI NHL) at King
      Abdulaziz University Hospital, Jeddah, and to compare our results to those
      reported in the literature. MATERIALS AND METHODS: Twenty-three adult patients
      with primary GI NHL diagnosed over a 5-year period (2000 through 2005) were
      retrospectively studied clinically and histopathologically. They were classified
      using the REAL/WHO histopathologic classification. RESULTS: Of the 23 patients
      with primary GI NHL, 14 (60.9%) were Saudis, with a male-to-female ratio of
      1.3:1. The mean age of male patients was 61. 3 years, ranging from 42-83 years
      with an SD of +/-13.09; while for females, the mean age was 64 years, ranging
      from 50-75 years with an SD of +/-9.14. Abdominal pain was the most common
      presenting symptom (78.3%), and the most common primary site was the stomach
      (73.9%), followed by the small bowel (13%). The most frequent histologic subtype
      was the diffuse large B cell lymphoma, accounting for 60.9% of all cases,
      followed by the marginal-zone cell lymphoma (MALT type), which was Helicobacter
      pylori associated (39.1%). A large proportion of patients with primary GI NHL had
      early disease (Stage IE - 20%, Stage IIE - 58.6%). With regards to treatment, 15
      patients (65.2%) had chemotherapy, while only 2 patients (8.7%) were treated by
      Helicobacter pylori eradication. The overall 5-year survival was 47.8%.
      CONCLUSION: The data demonstrated that primary GI NHL is more common among males,
      mainly in their sixth decade. Abdominal pain is the most common presenting
      symptom, with stomach being the most common involved site. Diffuse large B cell
      lymphoma is the most frequent histologic subtype, followed by extranodal marginal
      zone B cell lymphoma (MALT type), which was Helicobacter-associated. A majority
      of cases have early disease (stage IE and IIE), mostly treated by combination
      chemotherapy.

PMID- 19858598
TI  - The impact of functional dyspepsia on health-related quality of life in Saudi
      patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of non-ulcer
      dyspepsia (NUD) on health-related quality of life (HRQOL), which was assessed
      using the Nepean Dyspepsia Index, the Short Form-12 quality of life (QOL) scale,
      the general health questionnaire (GHQ-30) and the self-reporting questionnaire
      (SRQ-20). MATERIALS AND METHODS: Validated Arabic versions of the four scales
      were administered to 158 subjects (54 with NUD, 50 with gastroesophageal reflux
      disease [GERD] and 54 with no history of gastrointestinal [GI] disease), with a
      mean age of 46.6 years and SD 10.7. RESULTS: Subjects with NUD showed the poorest
      scores in all indices of general QOL and HRQOL. The differences between the NUD
      patients and the health control in all HRQOL indices were statistically
      significant (P < 0.05 to P < 0.001). Comparison between NUD and GERD patients
      showed significant differences only in the indices of psychological health
      related QOL ( P < 0.05) but not in the indices of other components of QOL,
      including physical health components. The study also showed that the women scored
      lower than men in HRQOL indices, particularly those of psychological and mental
      health components (P < 0.05 to P < 0.001). Finally, it was found that severity of
      symptoms is associated with the degree of impairments in HRQOL - (r = 0.69) was
      significant at (P < 0.001). CONCLUSION: Results of our study showed that HRQOL
      was significantly impaired in the NUD group. Psychological and mental health
      related quality of life was particularly impaired in this group compared to both
      normal patients and patients with similar GI disease. This magnitude of effects
      on HRQOL was also found to be associated with the severity of symptoms. The
      implications of these findings for the management of NUD are discussed.

PMID- 19858599
TI  - Laparoscopic cholecystectomy in children with sickle cell disease.
AB  - BACKGROUND: The aim of this study was to report the outcome of laparoscopic
      cholecystectomy in children with sickle cell disease and to compare the patients
      who had surgery as emergency with those who were operated as routine. MATERIALS
      AND METHODS: A total of 72 patients (males 48, females 24) less than 14 years of
      age (ranging between 6 and 14 years) underwent cholecystectomy at the King Fahad
      Hospital, Hofuf, in the last 5 years. The records of these patients were reviewed
      retrospectively, comparing the outcome of surgery in emergency and routine cases.
      RESULTS: The mean operating time and the mean hospital stay were longer in the
      emergency group (91.3 min, 8.5 days) compared to routine group (75.8 min, 4.5
      days respectively), with high incidence of postoperative complication in the
      emergency group. CONCLUSION: This study showed that elective laparoscopic
      cholecystectomy by an experienced surgeon and taking necessary precautions are
      the safety measures to be recommended at the time of diagnosis of cholelithiasis
      in sickle cell disease children.

PMID- 19858600
TI  - Laboratory predictors of advanced fibrosis in Saudi patients with chronic
      hepatitis B and C.
AB  - OBJECTIVE: To identify laboratory predictors of advanced fibrosis in Saudi
      Arabian patients with hepatitis B and C. MATERIALS AND METHODS: Histopathology
      reports were obtained on all patients who had liver biopsy in the last 5 years,
      and relevant laboratory data were collected. RESULTS: A total of 328 patients
      (246 with hepatitis C and 82 with hepatitis B) were included. With logistic
      regression analysis, four factors were found to be the best predictors of
      fibrosis, namely, platelet count, ALT, AST and GGT levels. An equation for
      calculating the risk of advanced fibrosis was developed. The model had a
      sensitivity of 62%, a specificity of 92.4% and an overall accuracy of 84%.
      CONCLUSION: Platelet count, ALT, AST and GGT levels were found to be the best
      predictors of advanced fibrosis on liver biopsy in Saudi patients with chronic
      hepatitis B and C. An equation was developed that helps in calculating this risk.

PMID- 19858601
TI  - Carcinoid of the Meckel's diverticulum: case report and review of literature.
AB  - We report a 19-year-old female admitted to the Emergency Room with excruciating
      right lower abdominal pain of 1-day duration. The abdominal examination revealed
      a soft, lax abdomen with rigidity and guarding in her right iliac fossa without
      abdominal defense. Apart from a leukocytosis of 18.3/mm3, the rest of her
      baseline investigations and imaging, including abdominal X-rays, abdominal and
      pelvic ultrasound and abdominal CT scan were unremarkable. Patient's persistent
      pain prompted the treating surgeon to undertake exploratory laparotomy, which
      disclosed an inflamed Meckel's diverticulum and a normal-looking appendix.
      Meckel's diverticulectomy along with appendectomy was performed. The
      histopathological report demonstrated carcinoid tumor in the Meckel's
      diverticulum with free resection margins, whereas appendix was reported to be
      normal. The patient had an uneventful recovery and was discharged home on the
      sixth postoperative day.

PMID- 19858602
TI  - Diagnosis and management of microscopic colitis.
AB  - Microscopic colitis (MC) in both of its forms, collagenous and lymphocytic
      colitis, is considered now an important cause of diarrhea in middle aged and
      elderly patients. In this entity, endoscopic and radiological examinations are
      normal while specific histological findings are seen on colonic biopsy. Once the
      diagnosis of MC is confirmed, a stepwise approach with medical therapy is
      suggested. Ruling out other causes of chronic diarrhea should be the initial
      step. Once the diagnosis of MC is confirmed, a stepwise treatment algorithm is
      suggested. In this review, I will introduce the entity of MC and describe the
      stepwise approach to diagnosis and management by reviewing the available
      evidence. The literature was reviewed regarding both collagenous colitis and
      lymphocystic colitits focusing on clinical trails. This was then critically
      examined and an approach to the diagnosis and management of microscopic colitis
      was suggested.

PMID- 19858603
TI  - Hepatitis B genotyping and its clinical implications.
AB  - Hepatitis B is a crucial medical problem in Saudi Arabia. Different hepatitis B
      virus genotypes have been discovered and have been shown to cluster in different
      areas of the world. Hepatitis B virus genotyping has received a lot of attention
      recently, and its clinical implications are being investigated extensively
      throughout the world. In this review, we will discuss the virology, epidemiology
      and clinical implications of the different hepatitis B genotypes.

PMID- 19858604
TI  - A 45-year-old man with a gastric mass. Gastric lipoma.

PMID- 19858605
TI  - Narrow band imaging: a wide field of possibilities.
AB  - The application of opto-electronic in video-endoscopes aims to improve accuracy
      in diagnosis, through image processing and digital technology. Narrow band
      imaging (NBI), one of the most recent techniques, consists of using interference
      filters for the illumination of the target in narrowed red, green, and blue
      (R/G/B) bands of the spectrum. This results in different images at distinct
      levels in the mucosa and increases the contrast of the epithelial surface and of
      the subjacent vascular network. NBI is combined to magnifying endoscopy with an
      optical zoom. After being studied in prototypes the opto-electronic technique,
      now available in the most recent models of video-endoscopes that use the
      sequential R/G/B system of illumination, should be adapted in the near future for
      the instruments utilizing the non-sequential system of illumination. This new
      technique aims to characterize the surface of the distinct types of digestive
      epithelia, including intestinal metaplasia in the Barrett's esophagus. The
      technique also allows characterizing the disorganization of the vascular pattern
      in inflammatory disorders of the digestive mucosa and in superficial neoplastic
      lesions in the esophagus, stomach, and large bowel.

PMID- 19858606
TI  - Role of endoscopic ultrasound in common bile duct stones.
AB  - When the clinical features strongly suggest the presence of bile duct stones,
      management is fairly straightforward; diagnostic and therapeutic endoscopic
      retrograde cholangiography (ERC) may in some cases constitute the entire
      strategy. Unfortunately, the clinical picture is often equivocal or uncertain.
      Although stones are unlikely to be present in the bile duct when the clinical
      index of suspicion is low, their presence can never be completely ruled out based
      on clinical and biochemical parameters. Thus, an accurate, noninvasive, reliable,
      and safe method for bile duct imaging would be highly advantageous. Low-risk
      tests, such as endoscopic ultrasound (EUS), are emerging as reliable substitutes
      for diagnostic ERC. This review highlights the technical aspects of examining the
      extra-hepatic biliary duct system and the performance and results of EUS in
      diagnosing patients who present with possible common bile duct stones.

PMID- 19858607
TI  - Protective effect of oleic acid against acute gastric mucosal lesions induced by
      ischemia-reperfusion in rat.
AB  - AIM: To assess the effect of Linoleic acid and oleic acid on gastric lesions
      induced by ischemia reperfusion. MATERIALS AND METHODS: Twenty-six fasted rats
      were subjected to 30 minutes of gastric ischemia in the presence of 100
      micromol/L hydrochloric acid and reperfusion periods of 60 minutes. The vascular
      permeability was quantified by measuring the extravasated Evans blue in the
      stomach. RESULTS: There were greater amount of leakage of Evans blue in gastric
      mucosa of rats treated with linoleic acid as compared to the control. Evans blue
      levels were significantly higher in gastric fluid as compared to the control. In
      contrast, Oleic acid significantly reduced the leakage of Evans blue in the
      gastric mucosa. CONCLUSION: Oleic acid played a significant role in protecting
      the gastric mucosa from ischemia/reperfusion injury. Replacement of LA by OA in
      the diet could be beneficial in protecting the gastric mucosa.

PMID- 19858608
TI  - Radiological response in Saudi patients undergoing transarterial
      chemoembolization for hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the second commonest cancer
      affecting males and the eighth most common one affecting females in Saudi Arabia.
      Transarterial chemoembolization (TACE) is currently considered the first line
      therapy for multifocal HCC in selected patients. OBJECTIVE: To evaluate HCC
      response to TACE based on triphasic computerized tomography (CT) of the liver
      obtained 6 weeks after the procedure. MATERIALS AND METHODS: A retrospective
      chart review of 15 patients who underwent TACE in King Khalid University Hospital
      for unresectable HCC. Patients were staged according to the Child-Pugh, Okuda,
      and CLIP scoring systems. The first triphasic CT of the liver after TACE was
      evaluated for Lipiodol uptake and interval change in tumor burden. RESULTS: The
      mean age was 63 years (40-82), 10 were males (66.7%), and five were females.
      About 11 patients had cirrhosis (73.3%). Eight patients (53.3%) were Child-Pugh
      class A while seven (46.7%) were Child-Pugh class B. One patient died and two
      were lost to follow up. Four patients had a complete response to TACE (26.7%),
      two had a partial response (13.3%), five showed no change (33.3%) and none showed
      progression of disease. Tumoral Lipiodol uptake in five patients was> 75%
      (33.3%), in two 75-50% (13.3%) while in four patients it was < 50% (26.7%).
      CONCLUSION: Our results show that TACE is an effective method of reducing the
      tumor burden in selected patients with unresectable HCC.

PMID- 19858609
TI  - Biliary ascariasis: report of a complicated case and literature review.
AB  - Invasion of the Ascaris worm into the biliary system leads to a wide variety of
      clinical syndromes. Most of the descriptions of the disease have originated from
      the developing world, where due to the environmental factors there is a high
      level of parasitism. An increased incidence of biliary ascariasis borne out of
      population migration and increased facilities for diagnosis has led to a renewal
      of interest in this disease in the developed world. Significant morbidity and
      mortality is associated with the concomitant complications, and early diagnosis
      and management is of utmost importance. Common disease presentations include
      biliary colic, obstructive jaundice, acalculous cholecystitis,
      choledocholithiasis, pancreatitis, and cholangitis. Although with a potential for
      serious mortality, pancreatitis, and cholangiocarcinoma constitute relatively
      less common threats. Recent advances in endoscopy have shifted the attention of
      this disease from the surgeon to the gastroenterologist and a consensus of
      opinion is arising for early intervention. We present here a patient with biliary
      ascariasis managed endoscopically and review the epidemiology, prevalence,
      clinical presentation, diagnosis, and management of this disease.

PMID- 19858610
TI  - A turtle in the belly: helminthoma.
AB  - A helminthoma is an inflammatory tumor of the bowel wall, which results when an
      intestinal worm or larva penetrates the wall of the gut, usually the cecum or
      colon. A helminthoma can occur in any country where infestation of the intestinal
      tract with worms is common. It has been seen most often in West and East Africa
      and parts of South America. In some parts of West Africa, this disease is well
      known to villagers, who describe it as having 'a turtle in the belly.' We report
      such a case with diagnostic dilemma.

PMID- 19858611
TI  - Angiogenesis and inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) has gained immense attention recently due
      primarily to increasing prevalence. The exact disease mechanism is still unknown.
      There is considerable evidence of interrelation between the mechanisms of
      angiogenesis and the chronic inflammation of IBD. This evidence was obtained from
      animal models of colitis and confirmed in human studies. Serum levels of vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) have
      been found to be significantly higher in patients with IBD than in controls. In
      addition, it was found that these factors correlate well with disease activity
      and decrease with the use of steroids. Therefore pharmacological inhibition of
      angiogenesis has the potential to be a therapeutic strategy in IBD.

PMID- 19858612
TI  - Gallstone ileus: a forgotten rare cause of intestinal obstruction.
AB  - Gallstone ileus is an uncommon complication of cholelithiasis, with a high
      morbidity and mortality rate - usually related to the delayed diagnosis of
      intestinal obstruction. Diagnosing gallstone ileus needs a high index of
      suspicion. A case of a gallstone ileus is reported. The clinical presentation,
      radiological features, intraoperative findings, operative procedure and
      literature review are presented.

PMID- 19858613
TI  - A rare cause of pain. Gossypiboma.

PMID- 19858614
TI  - Saudi gastroenterology association guidelines for the diagnosis and management of
      hepatocellular carcinoma: summary of recommendations.

PMID- 19858615
TI  - Asymptomatic gallstones: should we operate?
AB  - Symptomatic gallstones are easy to treat, unfortunately however asymptomatic
      gallstones are as easy to treat. This creates a problem for health care planners
      in the form of the financial implications involved, since asymptomatic gallstones
      are even more common than gallstones associated with symptoms and require no
      surgical intervention, while the funds diverted towards dealing with them drains
      the health care establishment of much needed funds in an era of costly health
      care. In this review we attempt to clarify the fact that asymptomatic gallstones
      need no intervention in most cases, thereby saving the patient unnecessary
      surgery and the health care establishment costs, both in the financial form and
      in manpower.

PMID- 19858616
TI  - Longitudinal pancreatico-gastrostomy: an effective means of pain control in
      chronic pancreatitis.
AB  - AIM: To assess the effectiveness of longitudinal pancreatico-gastrostomy (LPG) in
      relieving intractable abdominal pain in patients of chronic pancreatitis (CP)
      with dilated main pancreatic duct (MPD). MATERIALS AND METHODS: This prospective
      study was conducted from 1997-2005 at two university-affiliated hospitals in
      India. Ductal decompression by LPG was performed in 30 patients (26 males, 4
      females) suffering from intractable pain due to CP. The operative outcomes were
      classified as satisfactory and unsatisfactory according to whether the patients
      were completely/almost completely relieved of pain or continued to be troubled by
      pain. MAIN OUTCOME MEASURES: The main outcome measures were pain-relief,
      postoperative morbidity, and mortality. RESULTS: There was no postoperative
      mortality. Morbidity included pancreatic fistula in one patient, which closed
      spontaneously, gastric hemorrhage in two, prolonged ileus in one and wound
      infection in another. Twenty eight patients (93%) patients could be followed up
      till the end, the mean follow-up period being 23.8 (range 3-96) months. Operative
      result was satisfactory (no pain or mild pain) in 23 (82%) and unsatisfactory
      (moderate to severe pain) in 5 (18%) patients. Complete pain relief was seen in
      14 (50%) patients. The functional results, in terms of pain relief, were better
      in patients who had abstained from alcohol postoperatively. CONCLUSION: LPG is a
      good operative procedure to relieve intractable pain in patients of CP with an
      MPD diameter of at least 7 mm.

PMID- 19858617
TI  - Hepatitis C virus-associated thrombocytopenia is not related to serum
      thrombopoietin levels.
AB  - OBJECTIVE: Hepatitis C virus (HCV) infection is one of the most important health
      problems in Egypt. Thrombocytopenia is a common finding in subjects with chronic
      hepatitis. The precise etiology of this thrombocytopenia is still obscure. There
      is increasing interest in the potential role of thrombopoietin (TPO) as a cause
      of this thrombocytopenia. The aim of this work was to determine serum TPO levels
      in HCV-positive patients and to test the assumption that HCV-associated
      thrombocytopenia could be due to low TPO levels. MATERIALS AND METHODS: Forty
      patients with HCV infection were included in this study and classified into three
      groups according to the degree of thrombocytopenia (IA-mild, IB-moderate, II
      none). Twenty five healthy volunteers served as control (Group III). All patients
      and controls had undergone full clinical assessment and the following laboratory
      investigations: complete blood count, liver function tests, prothrombin time and
      concentration and serum TPO level. RESULTS: TPO levels were significantly
      elevated in Group IA as compared to the control group ( P <0.05). No significant
      difference was found between groups IA and II. TPO in Group IB was slightly, but
      insignificantly reduced compared to Group IA but did not differ statistically
      from the control or Group II. Significant negative correlation was found between
      serum TPO levels and platelet counts in Groups IA, IB and II (r=-0.421, P <0.05).
      No correlations were found between serum TPO levels and liver function tests or
      hematological parameters. CONCLUSION: An impaired TPO production did not explain
      the development of thrombocytopenia in HCV and other mechanisms must be involved.

PMID- 19858618
TI  - Prevalence of hepatitis B virus infection in the Gezira state of central Sudan.
AB  - AIM: This is a cross-sectional study to determine the prevalence and risk factors
      for transmission of hepatitis B virus (HBV) infection in the Gezira state of
      central Sudan prior to the introduction of blood screening and vaccination
      against HBV. MATERIALS AND METHODS: The study was carried out on the population
      of Um Zukra village in Gezira state of Central Sudan. The village was surveyed on
      five consecutive days in Dec 2000. Epidemiological characteristics were recorded
      and participants were interviewed for risk factors of viral hepatitis. Blood
      samples were then collected and tested for HBsAg and HBcAb. RESULTS: A total of
      404 subjects were screened with a mean age of 35 years; 54.9% were females, HBsAg
      and HBcAb were reactive in 6.9% and 47.5% of the studied population,
      respectively. Exposure to HBV increased with increasing age. The only significant
      risk factor for transmission of infection was a history of parenteral
      antischistosomal therapy. CONCLUSION: This study shows that prevalence of HBV
      infection is high in the studied population and it is hoped that introduction of
      blood screening and vaccination against HBV would decrease the carrier pool in
      the next few years.

PMID- 19858619
TI  - Clinico-pathological patterns of colorectal cancer in Saudi Arabia: younger with
      an advanced stage presentation.
AB  - AIM: Colorectal cancer (CRC) is the third most common cancer in the world. The
      aim of this study was to identify the clinical and pathological features of CRC
      in a tertiary care hospital in Saudi Arabia. MATERIALS AND METHODS: This is a
      retrospective study of all patients diagnosed to have CRC at King Khalid
      University Hospital in Riyadh, Saudi Arabia over a 10 year period (1995-2005).
      The data collected from medical files, endoscopy and imaging reports included
      age, gender, clinical presentation, smoking, relevant past or family history,
      site and size of the tumor, stage, carcinoembryonic antigen level and tumor
      grade. RESULTS: A total of 113 patients were included over the 10 year period.
      The average age at diagnosis was 55 years (S.D.=15), 58% of the patients were
      males and 42% were females. Thirty-seven percent of the patients were 50 years of
      age or younger. The most common clinical presentation was abdominal pain (68%)
      followed by rectal bleeding (62%) and weight loss (55%). Left-sided lesions and
      rectal cancer constituted 76% and 48% of all CRC tumors respectively. Sixty-eight
      percent of lesions were stage C and above. Forty-five percent of patients
      presented with complete large bowel obstruction. CONCLUSION: In this analysis, we
      found that Saudi patients were more likely to present with colorectal cancer at a
      more advanced stage of the disease and at younger ages compared to Western
      populations. This data suggests the need for a mass screening program to be
      implemented for this common and preventable cancer in Saudi Arabia.

PMID- 19858620
TI  - Candida esophagitis in achalasia cardia: case report and review of literature.
AB  - Candida albicans is by far the most common cause of infectious esophagitis. In
      most patients, this infection is secondary to an immuno-compromised state. In
      nearly 25% of the cases, underlying causes of esophageal stasis, e.g., achalasia
      and scleroderma, facilitate fungal colonization of the esophagus. Double contrast
      esophagography is a highly sensitive tool for diagnosing candida esophagitis.
      This report discusses the uncommon association of Candida esophagitis with
      achalasia cardia, their radiographic features and a short review of the available
      literature.

PMID- 19858621
TI  - Endoscopic ultrasound and hisopathologic correlates in eosinophilic
      gastroenteritis.
AB  - Eosinophilic gastroenteritis is a rare condition characterized by eosinophilic
      infiltration into any layer of stomach and intestine (mucosa, muscularis mucosa
      and serosa), usually in association with peripheral eosinophilia. In this case
      report, we present a patient with eosinophilic gastroenterocolitis who had a
      history of bronchial asthma and presented with abdominal pain. He was found to
      have peripheral eosinophilia, perforation and gangrenous bowel on performing
      surgery and tissue eosinophilia on histopathology examination. His endoscopic
      ultrasound (EUS) showed significant thickening of his antral and duodenal mucosal
      and submucosal layers which correlated well with the gross and microscopic
      pathology of the resected surgical specimen. This is the first case to
      demonstrate EUS abnormalities in this very rare disorder.

PMID- 19858622
TI  - Does Helicobacter pylori affect portal hypertensive gastropathy?
AB  - Helicobacter pylori (H. pylori) is a major etiological factor of peptic ulcer
      disease (PUD). It is supposed to be a risk factor for the more frequently
      encountered PUD in patients with liver cirrhosis. Several investigators have
      evaluated the effect of H. pylori on liver cirrhosis, portal hypertensive
      gastropathy (PHG) and encephalopathy with controversial results. Some reports
      have shown a higher seroprevalence and suggested a synergistic effect of H.
      pylori on liver cirrhosis and PHG. However, this increased prevalence is
      associated with a negative histology and is not influenced by the cause of
      cirrhosis, PHG, Child class or gender. Most studies have not found any
      correlation between H. pylori and PHG. In contrast, other studies have reported a
      markedly lower prevalence of H. pylori in cirrhotics with duodenal ulcer compared
      to controls. The aim of this article is to review the relationship between H.
      pylori infection and portal hypertensive gastropathy and the role of H. pylori
      eradication in cirrhotic patients.

PMID- 19858623
TI  - Adalimumab: a new tumor necrosis factor antagonist and the treatment of Crohn's
      disease.
AB  - Antibody-neutralization studies have implicated tumor necrosis factor-alpha (TNF
      alpha) and IL-12 p40 in the pathogenesis of Crohn's disease (CD). Many randomized
      controlled trials (RCTs) have demonstrated the efficacy of infliximab, a chimeric
      monoclonal antibody to TNF, in inducing and maintaining disease remission in
      patients with moderate to severe CD, including those with draining fistulas.
      However, infliximab is administered intravenously and is associated with
      immunological reactions and development of antibodies, and hence reduced
      efficacy. In this article, we describe the efficacy and safety profiles of a
      newly available recombinant, fully humanized, subcutaneously-administered, anti
      TNF-alpha monoclonal antibody, adalimumab (Humira) in patients with moderate to
      severe CD. Many recent RCTs have shown that adalimumab is not only similar to
      infliximab in the mode of action, efficacy, and safety, but it has the advantages
      of causing less anaphylactic or immunological reactions, being administered by
      the subcutaneous route, less need for hospitalization, and a half-life of 2 weeks
      that allows every other week dosage. Adalimumab has also shown some efficacy in
      infliximab-intolerant or resistant cases. Therefore, it represents a new horizon
      in the treatment of CD patients, and may reduce the number of patients who
      require surgical intervention.

PMID- 19858624
TI  - Hepatitis B genotyping and its clinical implications.

PMID- 19858625
TI  - Nonsteroidal, antiinflammatory drug-induced gastrointestinal injuries and related
      adverse reactions: epidemiology, pathogenesis and management.
AB  - A large proportion of the population all over the world consumes acetylsalicylic
      acid (ASA: aspirin) or other nonsteroidal, antiinflammatory drugs (NSAIDs). This
      is associated with a considerable morbidity and mortality. Elderly patients,
      patients with prior history of peptic ulcer disease (PUD) or its complications,
      those who require high doses of NSAIDs and those undergoing concomitant therapy
      with corticosteroids or anticoagulants, are at particularly high risk of
      developing gastroduodenal injuries and related adverse reactions. Gastroduodenal
      mucosal injuries induced by NSAIDs vary from subtle microscopic to gross
      macroscopic changes including ulcers. These injuries are induced by both topical
      and systemic actions of NSAIDs. Inhibition of gastroduodenal cyclooxygenase (COX)
      enzyme by NSAIDs is considered to be a major pathogenetic factor. Reactive oxygen
      species (ROS) appear also to play a significant role in the pathogenesis of
      mucosal injury. Withdrawal of NSAIDs is preferably the first therapeutic option;
      however, it is not feasible in the majority of patients. Therefore, several drugs
      including antisecretory drugs (ASDs-proton pump inhibitors and Histamine-2
      receptor antagonists) and misoprostol, a prostaglandin analog are used for the
      prevention and treatment of NSAID-induced gastroduodenal injuries. Among ASDs,
      proton pump inhibitors (PPIs) are the most commonly used drugs. The
      antiulcerogenic effect of PPIs is similar to that of misoprostol and superior to
      standard doses of histamine-2 receptor antagonists (H2-RAs). The adverse effects
      of m, isoprostol such as diarrhea, abdominal pain, nausea, flatulence, headache,
      dyspepsia, vomiting, constipation, abortifacient and teratogenicity limit its
      general use. Aside from their antisecretory action, PPIs also possess an
      antioxidative effect. PPI maintenance is recommended in chronic NSAID treatment
      in those with an increased risk of complications and is more effective than
      Helicobacter pylori eradication. Low PPI dosage maintenance is as effective as a
      standard dosage regimen. The effect of H. pylori eradication remains
      controversial. It is advocated in naive NSAID users, in chronic users with recent
      ulcer or ulcer complications and in those with an increased risk of ulcer and
      ulcer complications. In addition, some herbs have shown inhibition of gastric
      mucosal damage experimentally induced by necrotizing agents through their
      antisecretory and antioxidant properties.

PMID- 19858626
TI  - Stomach carcinoma in the Indian subcontinent: a 16-year trend.
AB  - BACKGROUND: Gastric malignancy is one of the most common causes for cancer
      related deaths. Reports from the west have shown a paradigm shift in the site of
      occurrence with malignancies of the gastric cardium increasing in frequency,
      reports which are contrary to information from the Middle East and South Asia.
      AIM: To determine trend changes in distribution of gastric malignancy between
      1989 and 2004 in the southern state of Tamil Nadu in India. MATERIALS AND
      METHODS: The study period was divided into four cohorts of four years each (1989
      1992, 1993-1996, 1997-2000 and 2001-2004) for the analysis of the changes in
      trend for subsite specificity, age and gender predilection. RESULTS: Clinically,
      there were no significant differences in the presenting symptoms or physical
      signs in the four cohorts. The antrum was the most common site of predilection,
      no site-specific change was noted and males continued to be more commonly
      affected of the two sexes. Gastric cancer was significantly higher above the age
      of 40 years in all the four subsites and cohorts. A decrease in the mean age was
      observed for men with cancers of the esophagogastric junction (OGJ) (P < 0.0001)
      and the proximal stomach (P < 0.0001), while junctional malignancy (P < 0.0001),
      cancers of the proximal stomach (P < 0.0001) and the antrum (P = 0.03) tended to
      occur progressively later among women. CONCLUSION: No change in site specificity
      or gender predilection for gastric adenocarcinoma has been noted in the past 16
      years. However, a gender-dependent paradigm shift in the mean age of presentation
      is discernible for cancers involving the OGJ, proximal stomach and antrum.

PMID- 19858627
TI  - Prognostic value of the monoethylglycinexylidide test in alcoholic cirrhosis.
AB  - BACKGROUND: The existing conventional liver function tests (LFTs) are indirect,
      inferior and have limited prognostic value. Therefore, the
      monoethylglycinexylidide (MEGX) test, which provides a direct measure of the
      actual functional state of the liver, is proposed as a real-time liver function
      test. The objective of this study was to assess the prognostic value of the MEGX
      test in cirrhosis by comparing it with Child-Turcotte-Pugh (CTP), the Mayo end
      stage liver disease (MELD) and discriminant function (DF) scores. MATERIALS AND
      METHODS: The study was carried out in Satara, India during the period of January
      2005 to June 2006 and included 79 adult alcoholic cirrhotic patients. The serum
      specimen from each patient was analyzed using conventional LFTs and the MEGX
      test. The prognostic scores-CTP, MELD and DF scores were calculated and
      statistical analyses was performed. RESULTS: Based on receiver operating
      characteristic (ROC) curves, the MELD score and MEGX60 showed excellent
      sensitivity and specificity. The comparison of area under ROC curves showed that
      MELD and MEGX60 had superior prognostic accuracy when compared to other scores.
      Kaplan-Meier survival curves for corresponding cutoff values clearly
      differentiated between patients with different survival times. CONCLUSION: The
      MEGX test has shown more sensitivity, specificity and accuracy than CTP and DF
      scores in determining cases with the possibility of three- and six-month
      survival. Thus, it can be concluded that MEGX test along with MELD, is an
      effective prognostic tool in the hands of clinicians for predicting short-term
      survival.

PMID- 19858628
TI  - Improper use of antisecretory drugs in a tertiary care teaching hospital: an
      observational study.
AB  - BACKGROUND: Antisecretory drugs (ASDs) are prescribed for preventing and treating
      nonsteroidal, antiinflammatory drug (NSAID)-induced gastrointestinal adverse
      effects and for stress ulcer prophylaxis (SUP). The suitability of long-term use
      of ASDs has been evaluated elsewhere but not in the Kingdom of Saudi Arabia
      (KSA). OBJECTIVES: To evaluate the improper use of pantoprazole, a proton pump
      inhibitor (PPI) and ranitidine, a histamine 2 (H2) receptor antagonist (H2RA);
      and to identify the associated factors for misuse of these two drugs at a
      referral hospital. MATERIALS AND METHODS: In 2006, a study was carried out at a
      tertiary care teaching hospital in Riyadh, where patients' medical charts were
      evaluated for two months. All hospitalized patients on ASDs drugs, aged 18 and
      above were identified. A standard criterion for proper use of ASDs was applied
      during evaluation. RESULTS: Of the 661 patients studied, the use of ASDs was more
      significant among males (57.9%) as compared to females. Proper use of ASDs show a
      significant increasing trend with patients' age. The use of ranitidine (56%) was
      significantly higher than that of pantoprazole (44%). The unjustified use of the
      drugs was observed in 282 (43%) patients. Improper use of the drugs decreased as
      duration of hospital stay lengthened. Two departments, namely medicine and
      surgery, were significantly associated with the prescription of the two drugs.
      Higher numbers of improper prescriptions of these drugs were associated with the
      surgery department (49.3%) than with the medicine department (38.2%). CONCLUSION:
      Improper use of ASDs was observed in 43% of the patients. Based on the results of
      this study, correct measures need to be implemented in order reduce the misuse of
      ASDs.

PMID- 19858629
TI  - Epidemiology of Shigella-associated diarrhea in Gorgan, north of Iran.
AB  - OBJECTIVE: Shigella is an important etiological agent for diarrhea and especially
      dysentery. Shigellosis is an intestinal infection that is a major public health
      problem in many developing countries. The aim of this study was to evaluate the
      prevalence of Shigella and its various species in diarrheal samples in Gorgan
      located in the north of Iran. MATERIALS AND METHODS: Between January-December
      2005, the epidemiology of Shigella- associated diarrhea was studied among 634
      patients in Gorgan. The diarrheal samples accompanied with a questionnaire, which
      contained the demographic and main symptoms of the patients, were transported to
      the laboratory and inoculated in different culture media. Colonies suspected to
      be of Shigella were detected using differential biochemical tests and
      subsequently, the serotype of Shigella was defined using antisera. RESULTS:
      Shigella was isolated from 56/634 diarrheal samples) (8.8%) of which S. sonnei
      was the predominant species (55%). Occurrence of Shigella was highest in the 2-5
      years' age group (70.9%) and highest in summer (73.2%) with the most frequent
      clinical manifestation being abdominal pain (67.8%). The prevalence of Shigella
      in males and females was 8 and 9.8% respectively, but this difference was not
      statistically significant. CONCLUSION: It has been shown that Shigella sonnei is
      the most common Shigella serogroup among 2-5 year-old children in Gorgan. It is
      therefore suggested that hygienic training be given to childcare attendants and
      the children themselves.

PMID- 19858630
TI  - Role of laparoscopy in the diagnosis of abdominal tuberculosis.
AB  - BACKGROUND: Tuberculosis continues to be a common disease in Iran and one of its
      presentations is abdominal tuberculosis. Histopathological confirmation of
      abdominal tuberculosis is difficult because of suboptional, noninvasive access to
      the pathology. Laparoscopy provides minimally invasive access to the peritoneum.
      AIM: The aim is to evaluate the role and importance of laparoscopy in the
      diagnosis of tuberculous peritonitis (TP). MATERIALS AND METHODS: A retrospective
      study on laparoscopy in Razi hospital of Rasht (in northern Iran) over a period
      of ten years showed that diagnostic laparoscopy was performed in 290 patients
      with abdominal pain, with or without ascites. Most cases revealed malignancy and
      we found 28 cases of abdominal tuberculosis. RESULTS: Macroscopic findings of TP
      were whitish granulations over both peritoneal layers, inflammatory adhesions on
      the visceral or parietal surface, thickening, hyperemia and retraction of the
      greater omentum and stalactic band which is characteristic of TP. Pathology
      confirmed TP in 28 cases and all patients had excellent response to medical
      therapy. CONCLUSION: Although other diagnostic methods of TP such as imaging,
      culture of ascitis and polymerase chain reaction (PCR) are used today,
      laparoscopy with tissue biopsy provided rapid and correct diagnosis of abdominal
      tuberculosis.

PMID- 19858631
TI  - Spontaneous rupture of the spleen: a case report and review of the literature.
AB  - Atraumatic rupture of the spleen is an uncommon but important clinical entity.
      The diagnosis is often missed due to the absence of any history of trauma.
      Various aspects of atraumatic rupture of the spleen including those of pathologic
      and spontaneous rupture have been reviewed. Primary angiosarcoma of the spleen is
      a very rare neoplasm with disastrous prognosis. Increased awareness of this
      condition would enhance early diagnosis and effective treatment.

PMID- 19858632
TI  - Acute pancreatitis: rare complication of chicken pox in an immunocompetent host.
AB  - Chicken pox is a highly contagious infection, caused by the varicella zoster
      virus. Although generally a benign, self-limited disease, varicella may be
      associated with serious complications especially in adults. We present acute
      pancreatitis- a rare complication, in otherwise healthy patients suffering from
      chicken pox. The presence of pancreatitis in association with chickenpox in
      immunocompetent patients can influence the outcome of the latter. This
      interesting case will hopefully increase awareness about this complication and
      its fatality in chicken pox.

PMID- 19858634
TI  - Primary omental torsion: a rare cause of acute abdomen.
AB  - Torsion of the greater omentum is a rare condition with symptoms resemble those
      of acute appendicitis and is infrequently diagnosed preoperatively. Treatment is
      surgical excision. Laparoscopic approach is an excellent diagnostic and
      therapeutic tool.

PMID- 19858633
TI  - Mesocolic hernia: an unusual internal hernia.
AB  - Internal hernia may be either congenital or acquired. Its incidence has been
      reported to be 1-2%. Herniation may be persistent or intermittent. Internal
      hernia is a rare cause of small bowel obstruction with a reported incidence of
      0.2-0.9%. The most common type is paraduodenal. Less common types include
      mesocolic hernia, which occurs following abdominal surgery. We report mesocolic
      hernias in two young patients, which presented as small bowel obstruction without
      any prior abdominal surgery.

PMID- 19858635
TI  - Fibroscan: a noninvasive test of liver fibrosis assessment.
AB  - Determination of the extent of progress of hepatic fibrosis is important in
      clinical practice, where it may reflect the severity of liver disease and predict
      response to treatment. Percutaneous liver biopsy is the gold standard for grading
      and staging of liver disease. However, liver biopsy is an invasive procedure with
      certain unavoidable risks and complications. Several methods have been studied in
      an attempt to reach a diagnosis of cirrhosis by noninvasive means. Fibroscan has
      been designed to quantify liver fibrosis by means of elastography and found to
      have reasonably good sensitivity and specificity patterns, especially in patients
      with advanced fibrosis and can be used as an alternative to liver biopsy.

PMID- 19858637
TI  - A 70 year old male with abdominal pain. Emphysematous cholecystitis.

PMID- 19858636
TI  - Probiotics: an overview and their role in inflammatory bowel disease.
AB  - In recent years, novel insights have been gained into the role of bacterial
      microflora in health and disease. Commensal flora manipulation by probiotic
      bacteria has been investigated in human and experimental inflammatory bowel
      disease. Various probiotic species have shown promise in the treatment of
      ulcerative colitis, Crohn's disease and pouchitis in small studies, although a
      clear clinical benefit remains to be established.

PMID- 19858638
TI  - Cutaneous manifestations of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) has many extraintestinal manifestations, and
      skin lesions are one of the most frequently described extraintestinal findings.
      Reports indicate an incidence of cutaneous manifestations ranging from 2 to 34%,
      Cutaneous manifestations are usually related to the activity of the bowel disease
      but may have an independent course. In this review we aim to address the various
      cutaneous manifestations associated with IBD, their impact on the disease course,
      and the treatment options available.

PMID- 19858639
TI  - Spontaneous rupture of the malarial spleen.
AB  - Spontaneous rupture of the spleen is a well-described occurrence in many
      diseases, being most commonly found in malaria. Exact incidence of this
      complication is not clear. In this article, we discuss pathology, diagnostic
      approach and therapeutic options in a patient with malarial splenic rupture.
      Ruptures of malarial spleens do heal and attempts at splenic lavage/conservative
      approach should be the aim in their management. Splenectomy should be reserved
      for those patients with severe rupture or those with continued or recurrent
      bleeding.

PMID- 19858640
TI  - Personality characteristics and irritable bowel syndrome in Shiraz, southern
      Iran.
AB  - BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is the most common functional
      gastrointestinal disorder, and its definite etiology is still unclear. It has
      been shown that personality characteristics can affect the disease presentation
      and attitude of patient toward symptoms. This study was undertaken to evaluate
      the personality characteristics in patients with IBS in Shiraz, southern Iran.
      MATERIALS AND METHODS: In a cross-sectional study, the personality
      characteristics of 60 patients with IBS and 55 healthy persons were compared
      using Minnesota II Multiphasic Personality Inventory (MMPI-2). The cases were
      selected from patients who were referred to the Mottahari clinic affiliated to
      the Shiraz University of Medical Sciences. RESULTS: The patients recorded the
      highest scores on the hypochondriasis and psychoasthenia scales. The scores of
      the patient on the scales of lie, infrequency, hypochondriasis, depression and
      hysteria showed significant elevation in comparison to those of the control
      group. Furthermore, the scores on clinical scales in male subjects were higher
      for psychopathic-deviate, paranoia and social introversion scales in comparison
      to the males in the control group. Female subjects recorded lower scores on the
      social introversion scale in comparison to the females in the control group. Male
      subjects also recorded a higher score on the psychopathic-deviate, paranoia,
      psychoasthenia and social introversion scales in comparison to females. Female
      subjects had a relatively higher score on the masculinity/feminity scale. Based
      on the clinical interview using DMS-IV criteria, the most prevalent symptoms were
      anxiety and depression in patients with IBS. CONCLUSION: Due to the high
      prevalence of anxiety and depression in patients with IBS, psychotherapy and
      pharmacotherapy of these patients is recommended.

PMID- 19858641
TI  - The effect of chronic consumption of paraoxon on basal and pentagastrin
      stimulated gastric acid and pepsin secretion in rats.
AB  - BACKGROUND/AIMS: Paraoxon, an organophosphate metabolite of the insecticide
      parathion inhibits the enzyme, acetylcholinesterase (Achase). Organophosphates
      affect the heart, visual system, nervous system and muscles. In this present
      study, we investigate the effects of the chronic consumption of paraoxon on
      gastric acid and pepsin secretion in N-mari rats. MATERIALS AND METHODS: This
      study was performed from April 2003 to May 2004 in the Physiology department of
      Baghiatalah University of Medical Sciences, Tehran, Iran. It was performed on
      three groups of female N-mari rats (10 /group) each weighing 200-250 g. The first
      group received 0.05 mg/kg/day paraoxon subcutaneously for one month. The second
      group received the same chronic doses of ethyl alcohol (96%) (solvent of
      paraoxon) and the third group (control) received no drugs. After tracheostomy and
      laparatomy, gastric secretions were collected with a tube via the duodenum.
      Pentagastrin (25 microg/kg, i.p.) was used as a gastric stimulator. Acid and
      pepsin secretions were measured by titration and the Anson method, respectively.
      The stages of the measurements were basal (first and second), stimulated and
      returned-basal. RESULTS: Basal acid secretion in the paraoxon group was greater
      than those in the alcohol and control groups (14.61 +/- 1.46, 7.18 +/- 0.28 and
      7.88 +/- 0.26 micromol/15 min, respectively, P < 0.001)). Although pentagastrin
      stimulated acid secretion in all the three groups was greater than that of the
      basal state, there were no significant differences among the three groups. Basal
      pepsin secretions in the paraoxon group were greater than those in the alcohol
      and control groups (2.97 +/- 0.32, 1.19 +/- 0.25 and 0.55 +/- 0.06 microg/15 min,
      respectively). Pentagastrin-stimulated pepsin secretion in the paraoxon group was
      significantly greater than those in the alcohol and control groups (3.22 +/-
      0.38, 2.22 +/- 0.46 and 1.09 +/- 0.66 microg/15 min, respectively, P < 0.001).
      CONCLUSION: Chronic exposure to paraoxon results in the increased secretion of
      gastric acid and pepsin.

PMID- 19858642
TI  - Correlation of gastroesophageal reflux disease with positive family history and
      headache in Shiraz city, southern Iran.
AB  - BACKGROUND/AIMS: To analyze the potential correlation of a positive family
      history of gastroesophageal reflux disease (GERD) and the history of headaches as
      a risk factor for and complication of the disease. MATERIALS AND METHODS: Three
      thousand and six hundred subjects were selected by cluster random sampling from
      all seven districts of Shiraz city, who were invited for interview. In five
      months, 1956 subjects participated in this study. A questionnaire organized into
      three sections of demographic, signs and symptoms of GERD, headache and family
      history of GERD was completed for each patient. Social and demographic variables
      were also recorded. RESULTS: The presence of GERD symptoms (72%) had a
      significant correlation with a positive family history of the disease ( P =
      0.000). Patients showed a variable frequency of headache, ranging from once daily
      (16.7%), three to five times a week (5.6%), once-twice a week (26.7%), once to
      three times a month (15.0%) and less than once a month (8.3%). There was a
      significant correlation between the headaches and the GERD symptoms ( P = 0.000).
      CONCLUSION: A positive family history of GERD can be considered as a risk factor
      for the disease and the presence of headache at the time of diagnosis as a
      complication of this disease. Therefore, in the management of GERD, attention
      should be given to these factors.

PMID- 19858643
TI  - Bile reflux measurement and its contribution to the severity of reflux
      esophagitis.
AB  - BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) may occur with acid, bile
      or in a mixed form. Endoscopic injury and mucosal metaplasia are a known sequelae
      to pathological GERD. The aim of the study was to determine the contribution of
      acid and duodenogastroesophageal reflux to endoscopic severity in patients with
      GERD and Barrett's esophagus (BE). MATERIALS AND METHODS: Ninety-one patients
      complaining of reflux symptoms were studied with upper gastrointestinal endoscopy
      and graded to nonerosive reflux disease (NERD), erosive reflux disease (ERD) and
      BE. Esophageal manometry and simultaneous ambulatory 24-h esophageal pH and
      bilirubin monitoring (Bilitec 2000) were performed in all patients. RESULTS:
      Seventy-one patients (78.0%) had ERD (Savary-Miller (grade I-III), 11 patients
      (12.1%) had NERD and 9 patients (9.9%) had BE, which were suspected
      endoscopically and diagnosed by histological esophageal biopsy. Combined 24-h
      esophageal bilirubin and pH monitoring revealed the following: 39 patients
      (42.9%) had mixed acid and bile reflux, 16 (17.6%) had pathological acid reflux
      alone, 18 (19.8%) had bile reflux alone and 18 patients (19.8%) showed no
      evidences of abnormal reflux. The percentage of the total time of the bilirubin
      absorbance > 0.14 in 71 patients with ERD was (8.18+/-11.28%) and in 9 patients
      with BE was (15.48+/-30.48%), which was significantly greater than that in 11
      patients with NERD (4.48+/-8.99%), P<0.05 and P=0.01 respectively. All the BE
      patients had abnormal esophageal bile reflux (bile alone (3 patients)); and mixed
      bile and acid (6 patients)); 44 of 71 patients (61.97%) with ERD had abnormal
      esophageal bile reflux (alone (13 patients) and mixed bile and acid (31
      patients)); meanwhile, 15 of them (21.2%) had abnormal acid exposure alone.
      Despite 11 patients having NERD, four patients (36.4%) had abnormal esophageal
      bile reflux and two of them had mixed reflux of bile with acid. CONCLUSION: We
      believe that the Bilitec method reliably identifies the presence of bilirubin and
      quantitatively detects the duodenogastroesophageal reflux of bile. Mixed reflux
      (acid and bile) is the chief pattern of reflux in our GERD patients. Bile reflux
      either alone or along with acid reflux contributes to the severity of erosive and
      nonerosive reflux diseases as well as in BE.

PMID- 19858644
TI  - Lipid peroxides in patients with inflammatory bowel disease.
AB  - BACKGROUND/AIMS: In this study, we aimed to determine the levels of
      malondialdehyde (MDA) in patients with inflammatory bowel disease (IBD) to
      investigate its contribution to tissue injury in IBD. MATERIALS AND METHODS:
      Forty-two patients with IBD (24 cases of Crohn's disease and 18 cases of
      ulcerative colitis) and 38 matched healthy subjects (control group) were
      considered for study. MDA levels were quantified by the measurement of
      thiobarbituric acid reactive substances. RESULTS: Plasma MDA levels of Crohn's
      disease patients were significantly higher than the control group, but not higher
      than the ulcerative colitis patients. Plasma MDA levels of patients with
      ulcerative colitis were higher than the control group but not significant.
      CONCLUSION: Increased levels of plasma MDA in IBD is an important indication of
      oxidative stress. Patients with Crohn's disease are more susceptible to oxidative
      stress than patients with ulcerative colitis.

PMID- 19858645
TI  - Primary hydatid cyst of the pancreas causing obstructive jaundice.
AB  - Primary hydatid cyst in the head of pancreas is rare. We report a case of a 26
      year-old patient, who presented with obstructive jaundice. The imaging studies,
      while demonstrating a fusiform dilatation of the common bile duct, was unhelpful
      in identifying the etiology. A pancreatic head cyst was discovered at the time of
      surgery. Diagnosis was confirmed by subsequent serology and identification of
      scolices on microscopic examination. From the reported data, we discuss the
      diagnostic and therapeutic modalities of this rare disease.

PMID- 19858646
TI  - Perforated diverticulum of the transverse colon.
AB  - Diverticula on the left side of the colon, especially in the sigmoid colon are a
      common occurrence in the West. However, right-sided diverticula are less common,
      being reported from Asian countries like China, Hong Kong, Japan, Singapore and
      India. Diverticula of the transverse colon are very rare with very few cases
      reported in literature. We report a case of perforated true diverticulum of the
      transverse colon in a sixty-two year-old lady.

PMID- 19858647
TI  - Concurrence of duodenal carcinoid and diffuse gastric adenocarcinoma: a rare
      phenomenon.
AB  - Synchronous tumors are well documented in the gastrointestinal tract. Various
      combinations have been studied. There are a few studies, which highlight the
      incidental finding of the yellow beauty-the "carcinoid" of the duodenum
      simultaneously occurring with the venomous "diffuse gastric adenocarcinoma". This
      is a report one such case in a 58 year-old man, who unfortunately died on the 4th
      postoperative day due to cardiopulmonary arrest.

PMID- 19858648
TI  - Albumin use is beneficial in cirrhotic patients.
AB  - There are several indications for the use of albumin in patients with
      decompensated cirrhosis and its role has existed in clinical practice for many
      decades. While the drug enjoys immense popularity, it yet attracts intensive
      debate amongst clinicians and pharmacologists alike. Regardless of its
      pharmacological properties, its clinical use in cirrhotic patients has its fair
      share of proponents and opponents. At present, in the setting of cirrhosis this
      debate centers around the treatment of spontaneous bacterial peritonitis, in
      patients with ascites treated with large volume paracentesis, and in those with
      hepato-renal syndrome. With the evolving evidence it has become imperative to
      shed old dogmas and address this issue in the light of evidence-based medicine.
      This article gives a representative view of albumin use in the above conditions
      across both sides of the clinical divide.

PMID- 19858649
TI  - Albumin use in cirrhotic patients: the case against.

PMID- 19858650
TI  - NOTES: evolving trends in endoscopic surgery.
AB  - Intraluminal endoscopic surgery is a recent innovation to minimally invasive
      surgery. This technique provides access to the peritoneal cavity through a
      natural orifice. The technique holds the promise for "incisionless," less
      invasive procedures without the risk of postoperative sequelae as in the standard
      surgical approach, particularly in high risk patients. The hope of combining the
      skill and experience of endoscopists and surgeons into a defined specialty has
      attracted worldwide attention. It is anticipated that the skill sets required
      will be a hybrid that includes laparoscopic skills as well as endoscopic
      expertise. The studies in animal models of natural orifice translumenal
      endoscopic surgery (NOTES) have demonstrated the safety and feasibility of
      various types of intraabdominal surgeries, including transgastric liver biopsy,
      cholecystectomy, tubal ligation and peritoneoscopy amongst others. This review
      discusses the evolution of NOTES, the types of procedures performed and the
      challenges that lie ahead in the further development of this technique.

PMID- 19858651
TI  - A 57-year old with abdominal lumps. Greater omental leiomyosarcomatosis.

PMID- 19858653
TI  - Perspectives on congenital abnormalities in the Third World.

PMID- 19858652
TI  - Single and unpaired sera tube widal agglutination test in enteric fever.

PMID- 19858654
TI  - Paediatric surgical research and publications in a developing country setting.
AB  - BACKGROUND: Research and publications are important in advancing quality of care
      as well as improving knowledge. Paediatric surgical research and publications in
      sub Saharan Africa have not been given much focused attention. MATERIALS AND
      METHODS: A retrospective review of published work in paediatric surgery from a
      major paediatric surgical centre in Nigeria from 1969 - 2005. All published work
      were reviewed for nature of research, organ/system and disease condition studied,
      nature of publication, volume of publication in relation to staffing as well as
      journal of publication. RESULTS: During the period there were 153 publications
      consisting of 86 (56.2%) original researches (77 of which were of retrospective
      study designs and 9 prospective), 56 (36.6%) case reports, 8 (5.2%) letters and 4
      (2.6%) review articles. None of the studies and publications was funded. More
      publications were made when the department of surgery was better staffed.
      Congenital anomalies (57, 37.3%) and surgical infections (28, 18.3%) were more
      frequently studied and in 82 (53.4%) publications the gastrointestinal tract was
      the focus. Most publications were in general medical journals (58, 37.9%) and
      general paediatric journals (54, 35.3%) but publications in paediatric surgical
      journals has continued to increase over the years and reached 25.9% by 2005. Some
      of the difficulties and challenges faced included lack of funding, poor staffing
      and inadequate facilities for laboratory research. CONCLUSION: Paediatric
      surgical research and publication in Nigeria is increasing but faces important
      limitations. Advocacy efforts are needed to improve funding. Networking as well
      as collaboration is necessary to improve the quality and spectrum of research.

PMID- 19858655
TI  - Tubularized incised plate urethroplasty with de-epithelialized flap.
AB  - AIM: To improve the results of tubularized plate urethroplasty by adding de
      epithelized flap. PATIENTS AND METHODS: Twenty-five cases of hypospadias who
      underwent Snodgrass urethroplasty using de-epithelialized flap were studied. The
      minimum period of follow-up in this series was 1 year. RESULTS: The resultant neo
      meatus was vertically oriented and slit like. Glans was conical which is
      cosmetically well accepted. Penile raphe was in the midline. None of the patient
      had residual chordee, penile torsion, or glans dehiscence. Excellent cosmetic
      results were observed in all cases. The complication rate in our series was 8%
      (two cases). Two patients developed fistula. CONCLUSION: De-epithelialized flap
      is a simple method to provide additional covering to the constructed neourethra
      after Snodgrass urethroplasty. It achieves our goal of noncrossing suture lines
      and providing maximum vascularity.

PMID- 19858656
TI  - Undescended testes in a developing country: a study of the management of 71
      patients.
AB  - BACKGROUND: A testis located outside the scrotum is prone to a lot of
      complications but early detection and correction give good result. The purpose of
      this study was to determine the pattern of presentation, complications recorded,
      the surgical treatment offered and outcome in a developing country. PATIENTS AND
      METHODS: A retrospective study of patients that presented with undescended testes
      at the University of Benin Teaching Hospital between January, 1997 and December,
      2006. RESULTS: A total of 76 orchidopexies and 10 orchidectomies were done on 71
      patients with undescended testes during the period. They were aged 9 months and
      47 years (mean 8.3 +/- 7.9 years) at surgery. Only 31 (43.7%) patients presented
      at age 5 years and below while 40 (56.3%) presented after 5 years. Seventy-two
      (83.7%) testes were palpable, ultrasound scan was used to locate 10 (11.6%),
      while 4 (4.7%) could only be located during groin exploration. Intraoperative
      assessment of the testes were 54 (62.8%) normal testicular volume, 22 (25.6%)
      reduced volume and 10 (11.6%) atretic. All those aged 5 years and below had
      normal/reduced testicular volume and all had orchidopexy whereas those above 5
      years with normal/reduced testicular volume had orchidopexy and those with
      atretic testis had orchidectomy. Post operatively, testicular growth was recorded
      only among the pre/pubertile boys, the testes retracted in two patients, scrotal
      skin infection in one, and intra scrotal haematoma in two. CONCLUSION: Delayed
      presentation resulted in morphological changes, increased complications, number
      of orchidectomy and reduced chance of testicular growth post orchidopexy.

PMID- 19858657
TI  - Epidemiology and management of paediatric head injury in eastern Nepal.
AB  - BACKGROUND: In children, majority of the head injuries are minor and management
      of critically ill children depend on a team approach using well-rehearsed,
      systematic management protocols that can be implemented within hours after
      injury. This study was carried out to ascertain the epidemiology and management
      of know the demographic profile and etiology of paediatric head injury in our
      setting, to know the clinical and radiological characteristics of head injury
      patients and to know the treatment options and outcome in paediatric head
      injuries. PATIENTS AND METHODS: Details of all children (age <16 years) with head
      injury seen in 1 year from 01.04.2005 to 31.03.2006 were retrospectively
      reviewed. Demographic profile, clinical details, investigations, treatment
      offered, and outcome were noted in a proforma. All data were analyzed by
      appropriate SPSS 11.0 statistical software tools. RESULTS: There were total 43
      patients. Young male children were more commonly affected in present series with
      a mean age of 7.67 years (median - 5.010 years), range 6 months-16 year. Fall
      (65.11%) was the most common mode of injury followed by road traffic accidents
      (RTAs) (25.6%). Mild head injuries (65.11%) were most common. Most common
      complaint was loss of consciousness and all the patients with severe head injury
      presented loss of consciousness. All patients with mild head showed good
      recovery; with moderate head injury, nine patients showed good recovery and three
      patients recovered with moderate disability. Patients with severe head injury
      (three patients) had 100% mortality. CONCLUSIONS: In urban areas of Nepal, RTAs
      like vehicular crashes, motor cycle accidents, and pedestrian hit by moving
      vehicle are more common and in rural areas fall from height are commoner. We need
      to develop child safety legislations and risk-specific intervention programs in
      Nepal.

PMID- 19858658
TI  - Clinical characteristics and outcome of surgical treatment of childhood
      rhabdomyosarcoma: a 7-year experience.
AB  - BACKGROUND: The aim of this study was to describe the outcome and determine the
      prognostic factors of outcome of childhood rhabdomyosarcoma in a tertiary
      hospital in a developing country. PATIENTS AND METHODS: This was a retrospective
      review of the clinical presentation, investigation, intervention, and treatment
      outcomes of children with rhabdomyosarcoma in our hospital over a 7-year period.
      Statistical analysis was performed using Chi-square test. RESULTS: A total of 18
      patients were identified with two-thirds being males (n = 12) with median age of
      7 years. Most of the children were below 10 years of age. Lower limbs tumour
      predominated (n = 6) followed by the upper limbs and head and neck (n = 4 each).
      Other sites included perianal/perineal (n = 3) and the orbit (n = 1). Two
      patients were Intergroup Rhabdomyosarcoma Study (IRS) group I, four group II,
      five group III, and seven group IV. Lymph node involvement was the commonest site
      of metastasis. Clinical group and stage was significantly more advanced in
      patients older than 10 years compared to younger than 10 years (P = 0.010, P =
      0.008, respectively). There were 12 patients with alveolar disease while six had
      embryonal type of rhabdomyosarcoma. Treatment was by combination chemotherapy,
      and surgical excision which was done primarily in 11, after chemotherapy in four,
      and after radiotherapy in one. Two had biopsy only. Five patients are alive, two
      of them without evidence of disease at average follow-up period of 2 years.
      CONCLUSION: Mortality from rhabdomyosarcoma in our setting is still unacceptably
      high. Late presentation may be the major contributor to high mortality. A more
      aggressive multimodality treatment approach may improve the outcome.

PMID- 19858659
TI  - Presentation and management outcome of childhood intussusception in Lagos: a
      prospective study.
AB  - BACKGROUND: Intussusception is the commonest cause of bowel obstruction in
      infancy and childhood. Early diagnosis and effective management have reduced its
      morbidity and mortality in developed countries. AIM: To document the
      presentation, management and treatment outcome of intussusceptions at the Lagos
      University Teaching Hospital (LUTH). PATIENTS AND METHODS: One hundred seventy
      four consecutive cases of this condition seen in children presenting at LUTH over
      a 5-year period were prospectively studied. Details of symptoms and signs, pre
      hospital care, treatment, and outcome in LUTH were documented. RESULTS: The triad
      of abdominal pain, bloody mucoid stools and palpable abdominal mass was seen in
      106 (61%) of the cases. One hundred thirty-five (77.6%) had been admitted and
      treated with antibiotics and intravenous fluids in primary healthcare centers for
      an average of 3 days before referral to the LUTH. Prolonged mean duration of
      recognizable symptoms of 3 days accounted for a 70.4% bowel resection rate. Wound
      infection occurred in 61 (36.1%), whereas fecal fistulae developed in six (3.6%),
      and burst abdomen in five (3%) of cases. Seven (4.1%) patients developed
      incisional herniae. Overall, mortality rate was 12.1%. CONCLUSION: The early
      symptoms of intussusception would seem to be missed by primary healthcare workers
      in Lagos, with consequently high morbidity and mortality. There is an urgent need
      to re-emphasize these symptoms to first-line healthcare providers and parents
      through public enlightenment campaigns.

PMID- 19858660
TI  - Short hospital stay versus day-care Mathieu hypospadias repair.
AB  - OBJECTIVE: This study compared the outcome of Mathieu repair between patients who
      went home within 24 hours on catheter and dressing and patients who were managed
      in hospital for 48 hours and had their catheters and dressings removed before
      going home. PATIENTS AND METHODS: A retrospective study of Mathieu hypospadias
      repair performed by the same surgeon for 11 years. Outcome measures were catheter
      and dressing related problems/complications. RESULTS: Sixty five patients were
      included in the study; 43(66.2%) were managed in-hospital for the first 48 hours
      (Group A), while 22(33.8%) were managed as day-care cases (Group B). Complication
      rate was 6(14.0%) and 3(13.6%) respectively, with fistula rate of 2(4.7%) in
      Group A and 1(4.5%) in Group B. CONCLUSION: Day care Mathieu repair of
      hypospadias does not increase the occurrence of complications.

PMID- 19858661
TI  - Male circumcision: an overview.
AB  - Circumcision is one of the common operations performed worldwide, for various
      reasons. Controversy exists as to whether circumcision is an operation. This
      literature review discusses the indications of circumcision, benefits and
      complications of circumcision, and alternatives to circumcision. Relevant
      articles on the benefits, complications, indications and alternative to
      circumcision from 1964 to 2005 were reviewed, from National Library of Medicine's
      Pubmed database. Additional articles were obtained from the reference lists of
      key articles and recent reviews.

PMID- 19858662
TI  - Congenital urethral hypoplasia with urethral fistula without imperforate anus:
      report of two cases.
AB  - Two male children with ano/recto-urethral fistula without anorectal malformation
      were managed in our institute. These patients had variable clinical
      manifestations and associated anomalies including congenital urethral hypoplasia,
      renal agenesis and patent urachus. Both were treated successfully according to
      their status of disease-complexes. This is to discuss these rare cases and its
      management with review of the literature.

PMID- 19858663
TI  - New method of hand anastomosis to complete the Duhamel operation for
      Hirschsprung's disease.
AB  - OBJECTIVE/PURPOSE: This paper describes a new method of hand anastomosis to
      complete the Duhamel operation for Hirschsprung's disease (HD). METHODOLOGY: All
      patients had diagnosis of Hirschsprung's disease confirmed by rectal biopsy and
      had defunctioning colostomy. At the definitive operation, the ganglionic bowel
      was brought down in a retro-rectal position and anastomosed at the anal canal
      just above the dentate line. At this anastomosis, the sutures at 11 and 1 o'clock
      were left long as stay sutures. An incision was then made down the new bowel at
      the antimesenteric border from the pelvic brim. Another incision was made down
      the back of the native rectum. A long-curved artery forceps was then passed into
      the incision in the native rectum out of the anal canal. This forceps was now
      hooked round the anastomosis at 12 o'clock and further pushed in until the point
      appears through the colotomy in the ganglionic bowel. The two layers of bowel
      between the forceps were incised. The forceps was now inserted to grab the long
      sutures at 11 o'clock and 1 o'clock in turn, and delivered through the pelvis.
      Anastomosis between the edges of the native rectum and the neorectum was then
      done with interrupted PDS inside and silk outside. RESULTS: Seven patients had
      the procedure done. Age ranged between 4 months and 4 years (mean 3.4 years).
      They were all males. One patient died early in the series from reaction to
      postoperative analgesia. Four older patients have bowel motions 2-3 times per
      day, do not soil at night, and are fully continent. CONCLUSION: This preliminary
      study shows that hand anastomosis could be used to complete Duhamel operation for
      patients with HD with satisfactory early results.

PMID- 19858664
TI  - Hydrometrocolpos from a low vaginal atresia: an uncommon cause of neonatal
      intestinal and urinary obstruction.
AB  - Neonatal hydrometrocolpos is a rare condition that follows congenital vaginal
      obstruction. Association with urinary obstruction and upper tract dilatation has
      been reported in some cases. Obstruction of the gastrointestinal tract without a
      coexisting bowel anomaly can also occur, but this is very rare. In some cases,
      preoperative diagnosis may be difficult. We describe our experience with a rare
      case of huge hydrometrocolpos presenting as neonatal intestinal and urinary
      obstruction.

PMID- 19858665
TI  - Perforated duodenal ulcer a rare cause of acute abdomen in infancy: a report of
      two cases.
AB  - Duodenal ulcer perforation is very uncommon in infants and children, that is why
      it is not usually considered in the differential diagnosis of acute abdomen in
      this age group. Moreover, the diagnosis of this condition is usually overlooked
      because of vague and variable symptoms and low index of suspicion on the part of
      the treating physicians. In this brief report, we are reporting two cases of
      successfully managed perforated duodenal ulcer in infancy.

PMID- 19858666
TI  - Trichobezoar with small bowel obstruction in children: two cases report.
AB  - A trichobezoar is a mass of cumulated hair within the gastrointestinal tract.
      Stomach is the common site of occurrence. Intestinal obstruction due to
      trichobezoar is extremely rare. The authors report two cases of a trichobezoar
      obstructing the terminal ileum in one and the jejunum in another.

PMID- 19858667
TI  - Congenital anterior penile isolated urethrocutaneous fistula: a case report.
AB  - Urethrocutaneous fistula is a common complication after hypospadias repair. If
      congenital, it is usually associated with other genitourinary and
      gastrointestinal anomalies. Isolated congenital urethral fistula is a very rare
      anomaly. We present a 4-year old circumcised boy with this unusual anomaly.
      Etiology, embryology, and management are discussed. We emphasize meticulous
      clinical examination for the diagnosis and to rule out other associated
      anomalies.

PMID- 19858668
TI  - Acute gastrointestinal emergencies requiring surgery in children.
AB  - BACKGROUND: Although abdominal pain is common in the paediatric age group,
      problems of misdiagnosis and serious consequences are more particular in an
      emergency setting. This study examined the aetiologies of acute abdominal
      emergencies in children. MATERIALS AND METHODS: This was a retrospective study of
      100 children below the age of 12 years presenting with acute abdominal
      emergencies (gastrointestinal) requiring operative interventions. All patients
      were operated on an emergency basis and the intraoperative findings were
      correlated with the clinical findings. RESULTS: Acute abdominal emergencies in
      the paediatric age group were heterogeneous, with a myriad of aetiological
      factors. Overall, 73% of patients were greater than 3 years of age. Early
      neonatal period formed the second most common group (12%). Acute appendicitis was
      the most common cause except in the infancy period where congenital abnormalities
      predominated. CONCLUSION: The correct diagnosis of acute abdomen in children
      requires attention to clinical details and a high degree of suspicion. Early
      surgical intervention in doubtful cases may be necessary to solve diagnostic
      problems.

PMID- 19858669
TI  - Intestinal obstruction in children due to Ascariasis: a tertiary health centre
      experience.
AB  - BACKGROUND: Ascariasis is the infestation by the largest intestinal nematode of
      man, a common problem in the tropics attributed to poor hygienic and low
      socioeconomic conditions. The aim of this research is to analyse the
      presentation, diagnosis and management of bowel obstruction caused by Ascaris
      lumbricoides, with special emphasis on the role of conservative management.
      MATERIALS AND METHODS: This is a single centre, two consultant based 5 year
      retrospective study of childhood intestinal obstruction due to worms. Diagnosis
      in the suspected patients was based on history of passage of worms per mouth or
      rectum and on x-ray and ultrasonography findings. Only the patients of intestinal
      obstruction with documented evidence of roundworm infestation were included in
      the study and were followed for one year. RESULTS: One hundred and three children
      with intestinal obstruction due to Ascaris lumbricoides were treated in the past
      five years at our centre. Abdominal pain was the most common presentation seen in
      96 children followed by vomiting in 77 children. 20 children had history of
      vomiting worms and another 43 had history of passing worms in stool. Abdominal
      tenderness was present in 50 children, 48 had abdominal distension of varying
      degree, 50 had abdominal mass due to worm bolus, and 16 had or developed
      abdominal guarding or rigidity. All the children were managed as for acute
      intestinal obstruction along with hypertonic saline enema. The aim of management
      was "to starve the worm and hydrate the patient". 87 patients (84.47%) responded
      favourably and were relieved of the obstruction by the conservative management,
      16 children (15.53%) had abdominal guarding or rigidity and underwent emergency
      exploration. CONCLUSION: Roundworm obstruction should be considered in the
      differential diagnoses of all cases of intestinal obstruction in children.
      Clinical history and examination along with X-ray and ultrasonography are very
      helpful for diagnosis of this surgical emergency. Most cases of intestinal
      obstruction due to Ascaris can be managed conservatively; however emergency
      surgery is needed in patients with abdominal guarding and rigidity.

PMID- 19858670
TI  - Multidisciplinary approach to expansion thoracoplasty for congenital spinal
      deformity: a preliminary report.
AB  - BACKGROUND: In children with congenital chest wall deformities, the vertical
      expandable prosthetic titanium Rib (VEPTR) has recently been developed to move
      the emphasis away from corrective spinal fusion, to expanding the deformed
      hemithorax. The aim of this paper is to demonstrate the need for paediatric
      surgeons in what is primarily an orthopaedic procedure. MATERIALS AND METHODS:
      All patients less than 5 years old who had primary congenital scoliosis with poor
      respiratory function and were treated by VEPTR at our institution in conjunction
      with the spinal orthopaedic surgeons were reviewed. RESULTS: All 6 cases required
      rib exposure and thoracostomy by a paediatric surgeon. One required exposure of
      the ribs only, 3 required an extrapleural thoracotomy and 2 required intrapleural
      thoracotomy with a patch repair of the rib space. None of the patients required
      blood transfusion and there were no early complications. All patients showed
      radiological improvement of their spinal and thoracic deformity as well as
      improvement in their respiratory function. CONCLUSION: Paediatric surgeons play
      an important role in the thoracic exposure required for this orthopaedic
      procedure. The benefit of a multidisciplinary approach is highlighted in this
      paper. The VEPTR implant may replace major spinal fusion surgery in this
      challenging group of patients.

PMID- 19858671
TI  - Pattern of childhood gynaecological presentations in a Nigerian tertiary health
      facility.
AB  - BACKGROUND: Gynaecological problems in children and adolescents are often both
      medically and psychologically unique and require a highly skilled approach
      differing from those utilized for an adult female population. There is paucity of
      data on childhood gynaecological problems in our environment. The purpose of this
      study was to document the prevalence and pattern of common gynaecological
      problems in the prepubertal child at Ahmadu Bello University Teaching Hospital
      Zaria, Northern Nigeria. MATERIALS AND METHODS: This was a retrospective study
      involving case file-based data analysis over a 10-year period (1995-2004) of 62
      children aged 1 month-12 years at the Gynaecology unit of Ahmadu Bello University
      Teaching Hospital Zaria, Northern Nigeria. RESULTS: Sixty-two children were seen,
      17 infants, 14 under 5 years of age, and the rest (31) were aged 6-12 years. The
      commonest condition was labial fusion (33.9%), urethral prolapse (14.5%), and
      suspected sexual assault (12%). Ambiguous genitalia (9.7%), vaginitis (6.5 %),
      and ovarian tumour (4.8%) were also encountered. CONCLUSION: Labial fusion,
      urethral prolapse, and suspected sexual assault are the commonest childhood
      gynaecological morbidities in Zaria. Provision of gynaecological services at
      every level of health care system to cater for young females is advocated.

PMID- 19858672
TI  - Day case inguinal hernia surgery in Nigerian children: prospective study.
AB  - BACKGROUND: There has been an increase in day case surgery for children
      worldwide, but there have been few reports of the practice (most of them being
      retrospective) by many of the surgical sub-specialties in the sub-region. The aim
      of this study was to document our experience with day case inguinal hernia
      surgery in a developing economy. MATERIALS AND METHODS: This was a prospective
      study of uncomplicated inguinal hernias treated as day case at OAUTHC between
      April 2004 and December 2004. Data were collected and analysed. RESULTS: Eighty
      eight patients were recruited into the study and none defaulted. There were 88
      patients, (M:F = 16.6:1). A majority (n = 54) of the hernias occurred on the
      right side, while just a few (n = 18) occurred on the left. There were 5 cases of
      wound infections giving an infection rate of 4.8%. In all, the morbidity
      following day case inguinal hernia surgery was slight and no patient required
      readmission into the hospital. CONCLUSION: Day case inguinal hernia surgery in
      children is safe and well accepted by patients and parents alike. Health
      institutions in which children with inguinal hernias still queue for long periods
      for space on the operation list need to adopt day case surgery for inguinal
      hernia in order to forestall the risk of their obstruction.

PMID- 19858673
TI  - Congenital constriction ring syndrome of the limbs: a prospective study of 16
      cases.
AB  - BACKGROUND: The congenital constriction ring syndrome is characterised by fibrous
      bands that encircle, strangle and even amputate parts of the foetus. It is a
      common condition amongst Ghanaian patients, but data on it is quite scanty.
      MATERIALS AND METHODS: A prospective study of patients presenting at a plastic
      surgical clinic in Ghana with the characteristics of the congenital constriction
      ring syndrome was undertaken. The patients were examined clinically and the
      findings recorded. An x-ray and clinical photograph of the affected limbs was
      taken. Treatment required several staged operations. Surgical correction of the
      constriction ring was done by excision and Z-plasty to prevent or alleviate
      lymphoedema, separation of distally fused digits and skin grafting of defect.
      RESULTS: Sixteen patients made up of 10 males and six females were seen. The age
      at presentation ranged from nine days to 12 years with a mean age of 14.6 months.
      Twenty-two limbs were affected, made up of four right upper limbs, six left upper
      limbs, seven right lower limbs and five left lower limbs. In the upper limb
      malformations involved 42 digits; in the lower limb malformations involved 33
      toes, one foot and five legs. Four main types of lesions were found: constriction
      rings, intrauterine amputations, acrosyndactyly, and simple syndactyly.
      CONCLUSION: Congenital constriction ring syndrome is of uncertain aetiology and
      could cause morbidity in the newborn. The syndrome and its complications are
      amenable to corrective surgery with good results. Early intervention is desirable
      for a successful outcome.

PMID- 19858675
TI  - Solid-pseudopapillary tumour of the pancreas: a report of a rare case.
AB  - The solid pseudopapillary tumour (SPT) of the pancreas is an uncommon cystic
      pancreatic neoplasm mostly seen in young females. We present a large SPT in a 16
      year-old female who presented with acute onset upper- and mid-quadrant abdominal
      pain associated with nausea and vomiting for 4 days. The lesion was demonstrated
      by abdominal ultrasound and by computed tomography, which was successfully
      removed surgically.

PMID- 19858674
TI  - Operative treatment of proximal humeral fractures in children: indications and
      results.
AB  - BACKGROUND: In most children proximal humeral fractures are treated non
      operatively with generally good results. This review discusses the indications of
      operative treatment and assesses the treatment results. MATERIALS AND METHODS:
      The charts of 20 patients (14 girls; mean age: 12.3+/- 2.8 years; range: 7-16
      years) with proximal humeral fractures who were operated on at our institution
      were reviewed from 1992 to 2002. RESULTS: There were five metaphyseal fractures
      and 15 physeal injuries which were angulated according to Neer-Horowitz score as
      grade III in four cases and grade IV in 16 cases with a mean angulation of 47.8+/
      39.1 degrees (range: 6-148 degrees). Associated lesions comprised open fracture
      and head trauma in two cases each. Patients with associated injuries were
      operated on primarily and the 16 others by secondary intention. All but one were
      reduced via an anterior approach with internal fixation. They were assessed for
      clinical and radiological healing at a mean follow up of 3.6 years ranging from
      1.2 to 7.8 years. CONCLUSION: Based on our study, surgical option is indicated
      for severely displaced and unstable fractures in older children and adolescents.

PMID- 19858676
TI  - Isolated congenital fusion of the gums.
AB  - Isolated congenital fusion of the gums is a rare anomaly. Early surgical
      treatment is indicated, as longstanding cases will impair normal feeding leading
      to nutritional and growth problems. We report the first case in the Yaounde
      Gynaeco-Obstetric and Paediatric Hospital, which was successfully managed
      surgically.

PMID- 19858677
TI  - Fetus-in-fetu.
AB  - INTRODUCTION: Fetus-in-fetu (FIF) is a pathological condition in which the
      malformed foetus is found in the body of its twin. We report this rare case of a
      3-month-old female baby whose diagnostic work-up suggested a mesenteric cyst but
      the mass at surgery was a FIF. DISCUSSION: Although current imaging modalities
      like computerized Tomography and magnetic resonance imaging have a higher
      Sensitivity for accurate delineation of tissues, cheaper imaging alternatives
      like plain abdomen and ultrasonography still have a place in the preoperative
      work-up of FIF.

PMID- 19858678
TI  - Fetus-in-fetu in a 6-month-old.
AB  - Fetus-in-fetu is a malformed parasitic monozygotic diamniotic twin found inside
      the body of the living child or adult. We report a case of lumbar mass having
      superficial rudimentary phallus, labioscrotal fold, testes, pedunculated thumb
      like digit and rudimentary pelvis in addition to bowel loops in a 6-month-old
      Nigerian girl. The mass was excised and the baby did well. We propose based on
      these that dizygotic parasitic foetiform twin could exist.

PMID- 19858679
TI  - Bilateral single system ectopic ureters: case report with literature review.
AB  - Bilateral single system ureteral ectopia (BSSEU) is one of the rarest entities in
      urology, with less than 80 cases reported so far. Incontinence resulting from the
      underlying anomaly can be devastating to the child. It is generally agreed that
      suitable urinary continence and long dry intervals are seldom obtainable because
      of poorly developed trigone and bladder neck area. We herein report a case of
      BSSEU managed by bilateral ureteric reimplantation, achieving satisfactory
      continence and bladder capacity without the need for urinary diversion or bladder
      neck reconstruction.

PMID- 19858680
TI  - Right lung agenesis.
AB  - Congenital pulmonary agenesis or aplasia is extremely rare. Although more than
      fifty percent of patients die before first five years of age, some individuals
      may remain asymptomatic throughout their life. A three-month-old female child
      with right pulmonary agenesis presented to us with severe respiratory distress.
      She was misdiagnosed as a case of foreign body bronchus at the peripheral health
      centre. Bronchoscopy confirmed the diagnosis and relieved the symptoms. It is
      recommended that invasive diagnostic procedures and prophylactic surgery should
      not be done in asymptomatic cases.

PMID- 19858681
TI  - Sirenomelia (mermaid syndrome): a rare anomaly.

PMID- 19858682
TI  - The magnitude of the problem of malnutrition in Europe.
AB  - A review of the publications on hospital malnutrition in Europe over the last 5
      years shows that the incidence and prevalence of malnutrition are still very
      high: 21 and 37%, respectively. The process of structured nutrition support is
      still far from being generally implemented, as based on the few studies
      available. As a result, malnutrition diagnosed on admission to hospital is still
      associated with adverse clinical outcome (increased length of stay and higher
      rates of complications).

PMID- 19858683
TI  - Malnutrition in North America: where have we been? Where are we going?
AB  - Malnutrition was first highlighted as a prevalent concern in hospital care more
      than 30 years ago. In response the nutrition support field grew precipitously but
      changes in the healthcare environment have culminated in a period of
      accountability and consolidation in nutrition support practice over the past
      decade. Evolving regulatory environment and reimbursement policies have had a
      profound impact upon nutrition support and these trends are likely to continue.
      Both undernutrition and overnutrition (obesity) remain prevalent concerns in
      North America. In particular the growing prevalence of overweight/obesity will
      have far-reaching implications for nutrition support practitioners and will
      require the development, testing, and validation of new standards of assessment,
      intervention, and monitoring. Adoption of common language and definitions by
      practitioners will facilitate standardized interventions, outcome measures, and
      high quality research. The future remains bright with tailored nutrition
      interventions poised to become a part of the individual medical treatment plan
      for specific patient conditions and genotypes. Future research priorities should
      include studies of nutritional modulation of inflammatory conditions with
      specific nutrients and functional foods and the testing of individualized
      nutritional interventions tailored to gene polymorphisms.

PMID- 19858684
TI  - The economics of malnutrition.
AB  - Despite extensive information on the adverse physical and psychological
      consequences of malnutrition, there is little information on its economic
      consequences. International studies suggest that disease-related malnutrition
      increases hospital costs by 30-70%. In the United Kingdom the Malnutrition
      Universal Screening Tool (MUST) was used as the basis for identifying the
      prevalence of malnutrition in various care settings. Malnutrition increased both
      the frequency of admissions and length of stay in hospitals, as well as the
      frequency of visits to a general practitioner and hospital outpatient visits, and
      residency in care homes. After assigning nationally representative costs to the
      utilization of these services, the public expenditure on disease-related
      malnutrition in the UK in 2003 was estimated to be more than GBP 7.3 billion. The
      large cost of disease-related malnutrition means that small fractional cost
      savings from intervention can result in substantial absolute cost savings. A
      summary of nutritional intervention studies with cost analyses (including meta
      analyses) and cost-effectiveness analyses are presented, and some of the clinical
      and ethical implications discussed.

PMID- 19858685
TI  - The need for consistent criteria for identifying malnutrition.
AB  - The lack of consistent criteria for diagnosing malnutrition and protein-energy
      malnutrition (PEM) creates problems in educating medical students and physicians,
      setting the parameters for observational and controlled clinical trials, and
      formulating clinical guidelines. There is no validated formal definition of
      malnutrition (or PEM), and the tools that have been developed to screen for it,
      or diagnose it, vary in their agreement. I make the following suggestions. First,
      avoid unqualified use of the term 'malnutrition', as it is ambiguous. Second,
      carefully distinguish between screening and diagnosis, which have different aims
      and implications. Third, consider the notion that in medicine the diagnosis of
      PEM is reached by 'narrative-interpretive' reasoning, which regards the disease
      as a pathophysiological entity in a specific clinical context. I recommend that
      the concept of PEM as a disease (not a score) be imbedded in teaching and the
      practice of medicine, and in the design of clinical trials and the setting of
      guidelines. Fourth, disagreements in screening-derived risk scores and
      uncertainty in diagnosis are difficult to avoid, but only in the grey zone. It
      would be prudent, at least until the greater medical world considers the
      nutritional paradigm plausible enough to invest in it, to enroll only patients
      who have unambiguously diagnosed PEM in prospective trials with hard clinical
      endpoints.

PMID- 19858686
TI  - Enteral nutrition reimbursement - the rationale for the policy: the US
      perspective.
AB  - Enteral nutrition (EN) is generally defined by third party payers as tube feeding
      for patients who cannot take food orally. EN is widely accepted in the United
      States as an effective, often life-sustaining therapy. Coverage and payment
      policies for EN differ among payers and settings. These differences often may
      depend on whether EN is reimbursed as a discrete therapy or subsumed into a
      larger benefit. In the US, the Medicare and Medicaid programs are the major
      public payers for EN. EN may be susceptible to overuse, especially in the long
      term care setting. The trends in coverage and payment for EN suggest tighter
      reimbursement; competitive bidding between suppliers and data-driven performance
      measurement and payments may be in the future for EN reimbursement.

PMID- 19858687
TI  - Enteral nutrition reimbursement - the rationale for the policy: the German
      perspective.
AB  - Both the German statutory and private health insurances cover enteral nutrition
      (EN) products. Approximately 100,000 patients receive reimbursed EN; 70% are tube
      fed for an average 9 months. 70% of the tube-fed patients are cared for in
      institutions (i.e. for the elderly) and 30% at home. The prescription and
      reimbursement of EN is covered by Volume Five of the Social Legislation Code
      (Social Code Book No. 5). Reimbursement for EN depends on medical prescription
      and is in principle guaranteed whenever normal food intake is impaired and
      modification of normal nutrition and other measurements do not improve
      nutritional status. It is unclear what effect the reform laws will have on EN but
      they may impact the prices for medical devices and negotiations between health
      insurance funds and product manufacturers.

PMID- 19858688
TI  - Food modification versus oral liquid nutrition supplementation.
AB  - Oral liquid nutrition supplements (ONS) are widely used in community, residential
      and healthcare settings. ONS are intended for individuals whose nutrient
      requirements cannot be achieved by conventional diet or food modification, or for
      the management of distinctive nutrient needs resulting from specific diseases
      and/or conditions. ONS appear to be most effective in patients with a body mass
      index of <or=20. Studies are needed to evaluate the clinical and functional
      efficacy of food-based versus ONS nutrition interventions.

PMID- 19858689
TI  - Cost-effectiveness analysis and health policy.
AB  - Economists have devised three main techniques to evaluate healthcare treatments:
      cost-benefit analysis, cost-effectiveness analysis and cost-utility analysis.
      Many countries have established regulatory authorities to examine the clinical
      safety, efficacy, and cost-effectiveness of a product. Currently, economic
      evaluations play a limited role in decision-making but may increase in importance
      as healthcare costs continue to rise.

PMID- 19858690
TI  - Implementing nutritional standards: the Scottish experience.
AB  - In the United Kingdom, 5% of the population are underweight or have features of
      malnutrition. The prevalence of malnutrition rises with age and is more common in
      the north of England than in the south, but comparable data are not available for
      Scotland. In 2003, the National Health Service Quality Improvement Scotland (NHS
      QIS) developed a standard for food, fluid and nutritional care in hospitals
      (FFNCH). In 2006, a peer review of Scottish health boards was published. The
      reviewers reported that all Scottish health boards had started to implement the
      standards, but not across all clinical areas. Every health board had set up a
      nutritional care group to oversee and advise on the implementation of the
      standards, but none had produced a financial framework to support the work of the
      groups. Most health boards had not fully developed a policy or strategic plan to
      improve nutritional care as required, and there was a shortage of specialist
      nutrition nurses and clinical and nutrition support teams to supervise the
      treatment of patients with complex nutritional needs. The Scottish experience
      emphasizes the size of the task that health services face to bring about change.

PMID- 19858691
TI  - Innovative models for clinical nutrition and financing.
AB  - By translating the principles of 'disease management' in an insurance
      environment, health insurance funds play an important role in the management of
      chronic diseases of their members. The independent health insurance funds in
      Belgium have developed an obesity disease management approach based on the
      integration of collective and individual prevention, early detection and
      immediate action. Incentive monetary prizes are provided if body mass index (BMI)
      is reduced by at least 5% following participation in the prescribed treatment
      plan. The independent health insurance funds plan to launch multimedia projects
      about the program to educate the target audience of lower income, less educated,
      obese patients.

PMID- 19858692
TI  - ENHA: what is it and what does it do? Strategies to make malnutrition a key
      priority in EU health policy.
AB  - In 2005, the European Nutrition for Health Alliance (ENHA, the Alliance) was
      established to raise awareness of the relevance and urgency of malnutrition and
      ensure that this important issue is included in policy discussions and
      appropriate action is taken by policymakers and stakeholders at EU and member
      state levels. Malnutrition remains under-recognized, under-detected and under
      managed across Europe, 4 years after the publication of the Call to Action
      resolution issued by the Council of Europe in 2003, on food and nutritional care
      in hospitals. The goal of the ENHA is to implement policy changes in nutrition
      and health at government and healthcare organizational levels. The value of
      specific evidence-based medical interventions must be demonstrated.

PMID- 19858693
TI  - Brief history of parenteral and enteral nutrition in the hospital in the USA.
AB  - The meteoric rise in parenteral and enteral nutrition was largely a consequence
      of the development of total parenteral nutrition and chemically defined diets in
      the late 1960s and early 1970s and the recognition of the extensive prevalence of
      protein calorie malnutrition associated with disease in this same period. The
      establishment of Nutrition Support Services (NSS) using the novel,
      multidisciplinary model of physician, clinical nurse specialist, pharmacist, and
      dietitian, which, at its peak in the 1990s, approached 550 well-established
      services in about 10% of the US acute care hospitals, also fostered growth. The
      American Society of Parenteral and Enteral Nutrition, a multidisciplinary society
      reflecting the interaction of these specialties, was established in 1976 and grew
      from less than 1,000 members to nearly 8,000 by 1990. Several developments in the
      1990s initially slowed and then stopped this growth. A system of payments, called
      diagnosis-related groups, put extreme cost constraints on hospital finances which
      often limited financial support for NSS teams, particularly the physician and
      nurse specialist members. Furthermore, as the concern for the nutritional status
      of patients spread to other specialties, critical care physicians, trauma
      surgeons, gastroenterologists, endocrinologists, and nephrologists often took
      responsibility for nutrition support in their area of expertise with a dwindling
      of the model of an internist or general surgeon with special skills in nutrition
      support playing the key MD role across the specialties. Nutrition support of the
      hospitalized patient has dramatically improved in the US over the past 35 years,
      but the loss of major benefits possible and unacceptable risks of invasive
      nutritional support if not delivered when appropriate, delivered without
      monitoring by nutrition experts, or employed where inappropriate or ineffective
      will require continued attention by medical authorities, hospitals, funding
      agencies, and industry in the future.

PMID- 19858694
TI  - What went right? The story of US Medicare Medical Nutrition Therapy.
AB  - When President Lyndon Johnson signed the Medicare and Medicaid bill into law in
      1965, it ended the 46-year campaign to enact a healthcare program for senior
      citizens and started what is now a 42-year effort by the American Dietetic
      Association (ADA) and its members to expand its coverage to 'nutrition services'
      for all appropriate diseases, disorders and conditions. In December 2000,
      Congress passed a Medicare Part B Medical Nutrition Therapy (MNT) provision,
      limited to patients with diabetes and/or renal disease, effective January 2002.
      In December 2003, the Medicare Modernization Act expanded access to MNT benefit
      and ADA continues to focus on the role of the registered dietician in MNT.
      Successful expansion of MNT benefits will require that ADA continues to
      demonstrate the cost-effectiveness and efficacy of nutrition counseling, as
      performed by the registered dietitian.

PMID- 19858695
TI  - Diagnosis and treatment of malignant pleural effusion: a systematic literature
      review and new approaches.
AB  - Malignant pleural effusion is a frequent complication in many types of tumors,
      and its presence indicates short expected survival. This review updates the
      current knowledge about diagnosis and management of malignant pleural effusion.
      In recent years, progress has been made in diagnosis through the use of new
      pathologic and radiologic approaches, such as the introduction of positron
      emission tomography-computed tomography, immunohistochemical marker combinations,
      and genetic studies to identify malignant cells. Treatment is always palliative.
      New promising drugs have been tested, but, awaiting randomized studies, talc
      pleurodesis is still the treatment of choice, although doubts remain about its
      safety. A long-term indwelling pleural catheter could be a valid alternative to
      talc pleurodesis in selected patients with trapped lung syndrome (a lung that
      fails to reexpand after drainage of pleural effusion) and short life expectancy.
      However, the correct treatment depends on several factors such as performance
      status, expected survival, presence of lung reexpansion following pleural
      drainage and comorbidities.

PMID- 19858696
TI  - Wide excision or Mohs micrographic surgery for the treatment of primary
      dermatofibrosarcoma protuberans.
AB  - OBJECTIVES: Dermatofibrosarcoma protuberans (DFSP) is a spindle cell tumor with a
      high local recurrence rate. Wide excision (WE) has been the standard treatment,
      but ideal margin width is poorly defined and Mohs micrographic surgery (MMS) has
      emerged as an alternative procedure. This study examines the use of WE versus MMS
      for the treatment of primary DFSP at a single institution. METHODS: Retrospective
      review of 48 primary DFSP cases treated from 1971 to 2006. Patient demographics,
      tumor features, surgical modality (WE vs. MMS), final pathology, and clinical
      outcome were evaluated. RESULTS: Twenty-eight patients underwent WE versus 20
      patients for MMS. Median age was 40 years. Median WE margin width was 2 cm. For
      MMS, the median number of layers required to clear the tumor was 2. Median
      maximal defect size was 10 cm for WE versus 9.4 cm for MMS. Advanced closure
      techniques were required for 18% WE versus 65% MMS (P = 0.001). Median operative
      time was significantly lower for WE at 77 minutes versus 257 minutes for MMS (P <
      0.001). Positive margins were present in 21.4% (6/28) WE versus 0% MMS (P =
      0.01). At a median follow-up of 49.9 months for WE and 40.4 months for MMS, local
      recurrence rates were 3.6% (1/28) and 0%, respectively (P = 1.0). CONCLUSIONS:
      From a surgical standpoint, WE was faster than MMS and resulted in a less complex
      defect/closure. Although positive margin resection was more common with WE, local
      control was ultimately similar for the 2 surgical modalities. The choice of WE
      versus MMS should be based on individualized patients/tumor characteristics and
      institutional expertise in these modalities.

PMID- 19858697
TI  - Thoracoscopic removal of mediastinal parathyroid glands: a critical appraisal of
      an emerging technique.
AB  - OBJECTIVE: To retrospectively evaluate the feasibility of thoracoscopic removal
      of mediastinal parathyroids. SUMMARY BACKGROUND DATA: Mediastinal exploration to
      resect ectopic parathyroid(s) is needed in approximately 2% of cases in
      hyperparathyroidism. Recent advances in thoracoscopic surgery allow for a
      minimally invasive treatment. METHODS: From 1999 through 2007, 13 patients
      affected by primary hyperparathyroidism (11 females, mean age 60 years, range: 22
      88) underwent thoracoscopic removal of mediastinal parathyroids. Scintigraphy
      produced positive results in 11 of 13 cases, computed tomography scan in 9 of 10,
      parathyroid hormone venous sampling in 10 of 10 patients, and magnetic resonance
      imaging in 5 of 7. Right thoracoscopic access was used in 9 patients, left in 4.
      Postoperative outcome was analyzed. RESULTS: Thoracoscopy enabled retrieval of
      mediastinal parathyroids in 10 of 13 (78%) cases. Mean operating time was 92
      minutes (range: 50-240). One procedure (8%) was converted. No perioperative
      deaths/major complications occurred. Mild complications occurred in 2 of 13 (15%)
      patients (pneumothorax/pneumonia, transient recurrent nerve palsy). Mean hospital
      stay was 4.7 days (range: 2-15). At a mean follow-up of 73 months (range: 16
      105), parathyroid hormone and calcium venous concentrations were high in 3
      patients. Unsuccessful procedures were related to doubtful or non-concordant
      preoperative localization. CONCLUSIONS: The thoracoscopic approach for
      mediastinal parathyroidectomy is feasible and safe. An accurate preoperative work
      up should be standardized to avoid useless procedures. In case of negative
      preoperative localization of the abnormal gland, thoracoscopy should not be
      adopted as a diagnostic tool.

PMID- 19858698
TI  - The impact of minimally invasive surgery on residents' open operative experience:
      analysis of two decades of national data.
AB  - SUMMARY: Over the past 2 decades, the operative experience of surgical residents
      has undergone major changes due to advances in the science and technology of
      surgery, treatment modality, growth of subspecialties, work hour regulations, and
      an emphasis on shorter hospitalization. METHOD: We performed a comprehensive
      statistical analysis of national data from ACGME (1998-2008), with a focus on
      changes in the component operations. RESULTS: Since 1993, when minimally invasive
      surgery was first recorded in ACGME data base, the US residents' open operative
      experience began to register a continuing decline. Today, a quarter of the
      resident's operations are closed procedures. During the same period, trauma
      operative experience has decreased by 50%. If the decline in open operations
      continues at this rate, within 10 years it will drop to less than 60% of that in
      1993. Gastrointestinal (especially biliary) operations are the most affected.
      Changes in ACGME data format of component operations made it difficult to
      determine the effect of work hour limit by looking at total operations alone.
      CONCLUSION: Training in open operative surgery, the foundation of the craft of
      surgery, is on the decline. Lack of operative trauma hurts intra-operative crisis
      management and decision making. These deficiencies deserve educational effort at
      a higher priority than accorded so far.

PMID- 19858699
TI  - Descending necrotizing mediastinitis: contemporary trends in etiology, diagnosis,
      management, and outcome.
AB  - OBJECTIVE: To evaluate contemporary trends in etiology, diagnosis, management,
      and outcome of descending necrotizing mediastinitis (DNM) and to draw the
      clinician's attention on this probably underappreciated disease. SUMMARY OF
      BACKGROUND DATA: An uncommon but one of the most serious forms of mediastinitis
      is DNM which is caused by downward spread of deep neck infections and arises as a
      major complication of "banal" odontogenic, pharyngeal, or cervicofacial foci. As
      most studies are based on small patient populations, current data on risk
      factors, etiology, and outcome vary significantly. Also, the optimal form of
      treatment remains controversial. METHODS: This retrospective study, which is the
      largest single-center study since 1960, is based on the management of 45 patients
      with DNM treated over a period of 12 years. Additionally, a meta-analysis of 26
      studies on DNM published between 1999 and 2008 was performed and compared with
      own data and 2 previous meta-analyses covering the interval from 1960 to 1998.
      RESULTS AND CONCLUSIONS: Today DNM most commonly arises from pharyngeal foci and
      mixed polymicrobial aerobic and anaerobic infections. Reduced tissue oxygenation
      and impaired immune function promotes its development. Most cases of DNM are
      limited to the upper mediastinum and can be adequately drained by a transcervical
      approach. Formal thoracotomy should be reserved for cases extending below the
      plane of the tracheal bifurcation. Although DNM remains an aggressive infection
      with high morbidity, a favorable outcome can now be obtained in 85% of patients,
      even with this selective approach. Early diagnosis and surgical intervention are
      crucial.

PMID- 19858700
TI  - Isolated gastrocnemius and soleal vein thrombosis: should these patients receive
      therapeutic anticoagulation?
AB  - OBJECTIVE: To determine the incidence of isolated gastrocnemius and soleal vein
      thrombosis (IGSVT) and the effect of anticoagulation on venous thromboembolism
      (VTE) events in patients with IGSVT. SUMMARY BACKGROUND DATA: Although IGSVT is
      diagnosed with increasing frequency, the clinical significance and optimal
      management remains unknown. METHODS: Vascular laboratory studies from April 2002
      to April 2007 were retrospectively reviewed to identify patients with IGSVT.
      Medical records were reviewed for demographic data, risk factors, treatment
      modalities, and VTE events. Univariate and multivariate analysis were performed.
      RESULTS: Of 38,426 lower extremity venous duplex studies, 406 patients with IGSVT
      were included in this study. Mean follow-up was 7.5 +/- 11 months. The overall
      incidence of VTE among the entire cohort was 18.7%, which included 3.9% pulmonary
      embolism and 16.3% deep venous thrombosis, with 1.5% of patients having both
      pulmonary embolism and deep venous thrombosis. However, the incidence of VTE was
      30% (36/119) and 27% (13/48) in patients who received no or prophylactic
      anticoagulation, respectively, but only 12% in patients treated with therapeutic
      anticoagulation (23/188; P = 0.0003). Multivariate analysis identified lack of
      therapeutic anticoagulation (P = 0.017) and history of VTE (P = 0.011) as
      independent predictors of subsequent VTE development. The rate of IGSVT
      resolution during follow up was 61.2% with therapeutic anticoagulation, but only
      40.0% and 41.0% with prophylactic or no anticoagulation, respectively (P =
      0.003). CONCLUSIONS: IGSVT is associated with a clinically significant rate of
      VTE which is dramatically reduced with therapeutic anticoagulation. These data
      warrant further investigation, taking into account the risks and benefits of
      anticoagulation.

PMID- 19858701
TI  - Remote ischemic preconditioning by hindlimb occlusion prevents liver
      ischemic/reperfusion injury: the role of High Mobility Group-Box 1.
AB  - INTRODUCTION: Hepatocellular injury caused by ischemia-reperfusion of the liver
      occurs in a number of clinical situations including major trauma, elective
      surgery of the liver, and liver transplantation. Several strategies have been
      used to prevent liver injury following ischemia-reperfusion (I/R). Among these,
      ischemic preconditioning has shown promise as a preventative approach. In this
      manuscript, we hypothesized that use of remote ischemic preconditioning by brief
      hindlimb ischemia might prevent liver dysfunction in a mouse model of liver I/R.
      METHODS: C57/B mice were subjected to 60 minutes of partial liver ischemia with
      or without antecedent hindlimb vascular I/R. Blood was drawn for serum alanine
      aminotransferase levels at times following liver reperfusion. Liver inflammation
      was assessed by measuring serum and liver tumor necrosis factor (TNF)-alpha
      protein and mRNA. The role of toll-like receptor 4 (TLR4) in mediating protection
      was determined using the mouse strain HeJ, which has a mutated TLR4. RESULTS:
      Antecedent hindlimb ischemia (10 minutes) lessened I/R-induced elevation of serum
      alanine aminotransferase compared with untreated I/R animals. This protection
      correlated with a reduction in serum TNF-alpha protein levels as well as liver
      TNF-alpha mRNA and apoptosis. High Mobility Group-Box 1 (HMG-B1) levels in the
      blood were elevated after hindlimb ischemia and injection of HMG-B1 prior to
      liver recapitulated the protective effect of hindlimb occlusion. TLR4-mutant HeJ
      mice did not demonstrate protection with hindlimb preconditioning. CONCLUSIONS:
      Brief hindlimb occlusion prevents liver I/R injury. This effect appears to be
      related to release of HMG-B1 and is dependent on the presence of a functional
      TLR4. Remote ischemia preconditioning represents a novel approach to preventing
      distant organ injury.

PMID- 19858702
TI  - Correlation between postoperative infective complications and long-term outcomes
      after hepatic resection for colorectal liver metastasis.
AB  - BACKGROUND: The impact of postoperative morbidity, and in particular infective
      complications on long-term outcomes, following hepatic resection for colorectal
      liver metastasis (CRLM) is not widely published. OBJECTIVE: To evaluate the
      effect of postoperative complications on disease recurrence and overall survival
      in patients undergoing hepatic resection for CRLM. METHODS: All patients
      undergoing hepatic resection for CRLM from January 1993 and March 2007 were
      identified, and postoperative complications analyzed. Patients who died of
      postoperative complications within 30 days of surgery were excluded form the
      study. Postoperative complications were graded using a validated system of
      classification. Complications were further classified into infective and
      noninfective complication groups and the primary end points of the study were
      disease free survival (DFS) and overall survival (OS) at 5 years. RESULT: A total
      of 705 patients underwent hepatic resection in the study period. Median follow-up
      was 38 months. Operative morbidity and mortality were 28% and 3.6%, respectively.
      The total number of patients was 197 (28%) with complications, and 508 (72%)
      without complications. The 5 year DFS and OS for those with and without
      complications were: 13% versus 26% (P < 0.001) and 24% versus 37% (P < 0.001),
      respectively. Multivariate analysis showed inflammatory response to tumor score,
      blood transfusion, tumor number >8, and postoperative sepsis to be independent
      factors associated with DFS, and inflammatory response to tumor, tumor number >8,
      and postoperative sepsis to be independent predictors for OS. Intra-abdominal and
      respiratory infection but not wound infections were associated with poorer long
      term outcomes. CONCLUSIONS: Postoperative complications influence long-term
      outcomes in hepatic resection for CRLM. Specifically, postoperative sepsis is an
      independent predictor of disease free and overall survival. Thorough preoperative
      optimization, meticulous surgical technique and careful management in the
      postoperative period may reduce the incidence of these complications and
      influence long-term outcomes.

PMID- 19858703
TI  - A multicenter, randomized efficacy study of the EndoBarrier Gastrointestinal
      Liner for presurgical weight loss prior to bariatric surgery.
AB  - BACKGROUND: The endoscopically placed duodenal-jejunal bypass sleeve or
      EndoBarrier Gastrointestinal Liner has been designed to achieve weight loss in
      morbidly obese patients. We report on the first European experience with this
      device. METHODS: A multicenter, randomized clinical trial was performed. Forty
      one patients were included and 30 underwent sleeve implantation. Eleven patients
      served as a diet control group. All patients followed the same low-calorie diet
      during the study period. The purpose of the study was to determine the safety and
      efficacy of the device. RESULTS: Twenty-six devices were successfully implanted.
      In 4 patients, implantation could not be achieved. Four devices were explanted
      prior to the initial protocol end point because of migration (1), dislocation of
      the anchor (1), sleeve obstruction (1), and continuous epigastric pain (1). The
      remaining patients all completed the study. Mean procedure time was 35 minutes
      (range: 12-102 minutes) for a successful implantation and 17 minutes (range: 5-99
      minutes) for explantation. There were no procedure related adverse events. During
      the study period the 26 duodenal-jejunal bypass sleeve patients (100%) had at
      least one adverse event, mainly abdominal pain and nausea during the first week
      after implantation. Initial mean body mass index (BMI, kg/m2) was 48.9 and 47.4
      kg/m2 for the device and control patients, respectively. Mean excess weight loss
      after 3 months was 19.0% for device patients versus 6.9% for control patients (P
      < 0.002). Absolute change in BMI at 3 months was 5.5 and 1.9 kg/m2, respectively.
      Type 2 diabetes mellitus was present at baseline in 8 patients of the device
      group and improved in 7 patients during the study period (lower glucose levels,
      HbA1c, and medication requirements). CONCLUSION: The EndoBarrier Gastrointestinal
      Liner is a feasible and safe noninvasive device with excellent short-term weight
      loss results. The device also has a significant positive effect on type 2
      diabetes mellitus. Long-term randomized and sham studies for weight loss and
      treatment of diabetes are necessary to determine the role of the device in the
      treatment of morbid obesity.This study was registered at www.clinicaltrials.gov
      (registration number: NCT00830440).

PMID- 19858704
TI  - Radiofrequency ablation as first-line treatment in patients with early colorectal
      liver metastases amenable to surgery.
AB  - OBJECTIVE: Aiming at avoidance of futile surgery, we have tested whether
      radiofrequency ablation (RFA) may be used as first-line treatment in patients
      with colorectal metastases (CRLM) occurring within the first year after
      colorectal surgery. SUMMARY BACKGROUND DATA: Surgical resection is the standard
      treatment in patients with CRLM. Major retrospective analyses have identified the
      interval between colorectal surgery and the occurrence of CRLM to be of
      prognostic importance. So far, it is unknown whether survival of the respective
      patients is hampered if RFA is used as first-line treatment. METHODS: According
      to a clinical pathway, we have treated patients with CRLM detected within the
      first year after colorectal surgery preferentially by RFA (n=28). Resection
      (n=82) was performed in patients who were deemed not amenable to RFA due to
      number, size, or location of metastatic lesions. The diameter of lesions differed
      between the groups. All other characteristics of patients and lesions were
      comparable. Local recurrence and new hepatic lesions were treated with repeated
      RFA or surgery whenever possible. RESULTS: Local recurrence at the site of
      ablation or resection occurred in 32% and 4% (P<0.001), new metastases apart from
      the site of previous treatment in 50% and 34% (P=0.179), and systemic recurrence
      in 32% and 37% (P=0.820) of the patients after RFA and surgery, respectively.
      Time to progression was significantly shorter in patients primarily treated with
      RFA (203 vs. 416 days; P=0.017). After primary treatment, 9 RFA patients and 8
      surgery patients were amenable to repeated RFA or repeated surgery resulting in
      identical rates of disease-free patients and identical 3-year overall survival in
      both treatment groups: 67% and 60%, respectively; P=0.93. CONCLUSIONS: Despite
      striking differences in local tumor recurrence and shorter time to progression,
      survival in patients with early CRLM does not depend on the mode of primary
      hepatic treatment.

PMID- 19858705
TI  - Live donor liver transplantation in high MELD score recipients.
AB  - BACKGROUND: In 2002, the New York State Committee on Quality Improvement in
      Living Liver Donation prohibited live liver donation for potential recipients
      with Model for End-stage Liver Disease (MELD) scores greater than 25. Despite the
      paucity of evidence to support this recommendation, many centers in North America
      remain reluctant to offer living donor (LD) to patients with moderate to high
      MELD scores. METHODS: We analyzed 271 consecutive adult-to-adult right lobe LD
      liver transplants performed at our institution between 2002 and 2008 to study the
      relationship, between recipient MELD scores and the outcome of LD liver
      transplantation. The recipients were categorized according to their MELD score
      into a low (Low: <25)and high (Hi: >or=25) MELD group. We compared short-term
      donor morbidity, graft loss within 30 days, length of hospital stay, biochemical
      markers of hepatocyte injury and graft function, and 90 day posttransplant
      complications including infection, rejection, bleeding, and renal failure. Long
      term posttransplant outcome was measured by graft and patient survival after 1-,
      3-, and 5-years. RESULTS: Donor and recipient characteristics were similar
      between groups. Donor outcomes were similar in both groups. Peak recipient
      aspartat aminotransferase, alanine aminotransferase, and length of hospital stay
      were similar between both groups. The proportional decrease in postoperative INR
      and creatinine within the first week was greater in the high versus low MELD
      score group. High MELD score recipients had more frequent postoperative pneumonia
      (Low: 2.2% vs. Hi: 14%, P = 0.003), while no differences were observed in rates
      of biliary complications, rejection, renal failure, or overall infections.
      Recipients with a MELD <25 versus >or=25 had a similar 1-year (Low: 92% vs. Hi:
      83%), 3-year (Low: 86% vs. Hi: 80%), and 5-year (Low: 78% vs. Hi: 80%) graft
      survival after LD liver transplantation (P = 0.51). CONCLUSION: LD liver
      transplantation can provide excellent graft function and survival rates in high
      MELD score recipients. Thus, when deceased donor organs are scare, a high MELD
      score alone should not be an absolute contraindication to living liver donation.

PMID- 19858706
TI  - The association between cholecystectomy and gastroesophageal reflux symptoms: a
      prospective controlled study.
AB  - OBJECTIVE: A large controlled prospective observational study to compare pre- and
      postsurgery changes in reflux symptoms between cholecystectomy and hernia repair
      surgery patients. SUMMARY BACKGROUND DATA: Six studies have suggested that
      gastroesophageal reflux worsens after cholecystectomy. However, all these studies
      had design limitations. METHODS: We recruited 302 patients scheduled to undergo
      elective cholecystectomy (study group) or hernia repair (controls) at 2
      hospitals. Both groups filled out the validated Reflux Symptom Score (RSS) and
      Gastrointestinal Symptom Rating Scale (GSRS) questionnaires 1 to 15 days prior to
      and 4 to 12 weeks after the operation. Changes in symptom scores between the pre
      and postsurgery assessments were measured, and compared between the 2 groups.
      RESULTS: Baseline RSS and GSRS reflux subscores were higher in the study group
      than controls (1.44 vs. 1.02 and 1.91 vs. 1.43, respectively; P < 0.05). There
      were no significant differences in any of the symptom score changes between the 2
      groups except for the GSRS pain subscore, which decreased more in the study group
      than the control group (-0.59 vs. -0.10; P < 0.001). With regard to reflux, the
      RSS decreased by -0.34 in the study group and -0.14 in controls (P = 0.27), while
      the GSRS reflux subscore decreased by -0.32 in the study group and -0.05 in
      controls (P = 0.12). GSRS diarrhea and constipation subscores decreased slightly
      after surgery, to the same extent in both groups. CONCLUSIONS: This large
      prospective controlled study, the only one using validated reflux symptom
      questionnaires, shows that cholecystectomy does not lead to an increase in reflux
      symptoms. As expected, GSRS pain subscores were decreased in the cholecystectomy
      group but not the controls.

PMID- 19858707
TI  - A new systematic small for size resection for liver tumors invading the middle
      hepatic vein at its caval confluence: mini-mesohepatectomy.
AB  - OBJECTIVE: We describe a new ultrasound guided conservative procedure for
      patients with liver tumors invading the middle hepatic vein (MHV) at its caval
      confluence. SUMMARY BACKGROUND DATA: Morbidity and mortality for major
      hepatectomies are not negligible. However, when tumors invade the MHV at the
      caval confluence, major surgery is usually recommended. METHODS: Patients
      included in this study were those with tumors invading the MHV at its hepato
      caval confluence (within 4 cm). Minimum follow-up was established at 6-months
      from surgery. Among 284 consecutive hepatectomies, 17 (6%) met the inclusion
      criteria. Partial sparing of segments 4, 5, and 8 was established
      intraoperatively, based on color-Doppler IOUS findings (NCT00600522 on
      ClinicalTrials.gov). RESULTS: In all the 17 patients at least one of the color
      Doppler IOUS criteria was disclosed, and limited resections of just segments 4sup
      and 8 were always feasible. The MHV tract involved was always resected. Seven
      patients had single tumor removed and 10 multiple: total number of resected
      tumors was 58 (median: 2; range: 1-18). There were no postoperative mortality and
      major morbidity. Overall morbidity occurred in 3 (18%) patients. Median blood
      loss was 250 (range: 50-1000). One patient (6%) received blood transfusion. No
      local recurrences were observed (median follow-up: 26 months). CONCLUSIONS: IOUS
      assistance systematically allows conservative resection of liver tumor invading
      the MHV at caval confluence. This drastically limits the need for larger
      resections, and further broadens the role of IOUS in optimizing the surgical
      strategy.

PMID- 19858708
TI  - Frequency of extrapancreatic neoplasms in intraductal papillary mucinous neoplasm
      of the pancreas: implications for management.
AB  - OBJECTIVE: To estimate the frequency of extrapancreatic neoplasms in patients
      with IPMN compared with those with ductal pancreatic cancer and a general
      referral population. SUMMARY BACKGROUND DATA: Several studies have reported an
      increased risk of extrapancreatic neoplasms in patients with IPMN, but these
      studies focused only on those patients who underwent resection and excluded those
      patients treated nonoperatively. METHODS: All patients diagnosed with IPMN at
      Mayo Clinic from 1994 to 2006 were identified. Two control groups consisting of
      Group 1-patients with a diagnosis of ductal pancreatic adenocarcinoma (1:1) and
      Group 2-a general referral population (3:1) were matched for gender and age at
      diagnosis, year of registration, and residence. Logistic regression was used to
      assess the risk of a diagnosis of extrapancreatic neoplasms among cases versus
      controls. RESULTS: There were 471 cases, 471 patients in Group 1, and 1413
      patients in Group 2. The proportion of IPMN patients having any extrapancreatic
      neoplasm diagnosed before or coincident to the index date was 52% (95% CI, 47%
      56%), compared with 36% (95% CI, 32%-41%) in Group 1 (P < 0.001), and 43% (95%
      CI, 41%-46%) in Group 2 (P = 0.002). Benign neoplasms most frequent in the IPMN
      group were colonic polyps (n = 114) and Barrett's neoplasia (n = 18). The most
      common malignant neoplasms were nonmelanoma skin (n = 35), breast (n = 24),
      prostate (n = 24), colorectal cancers (n = 19), and carcinoid neoplasms (n = 6).
      CONCLUSIONS: Patients with IPMN have increased risk of harboring extrapancreatic
      neoplasms. Based on the frequency of colonic polyps, screening colonoscopy should
      be considered in all patients with IPMN.

PMID- 19858710
TI  - Is gemcitabine an option in BCG-refractory nonmuscle-invasive bladder cancer? A
      single-arm prospective trial.
AB  - The objective of this study was to evaluate intravesical gemcitabine in high-risk
      nonmuscle-invasive bladder cancer (NMIBC) refractory to bacillus Calmette-Guerin
      (BCG). This was a prospective multicentre single-arm trial. Eligible patients
      were those with high-risk NMIBC refractory to BCG therapy, for which radical
      cystectomy was indicated but not conducted because of patient refusal or
      ineligibility. Patients received intravesical gemcitabine twice weekly at a dose
      of 2000 mg/50 ml for 6 weeks, and then weekly for 3 weeks at 3, 6, and 12 months.
      Outcome measures were recurrence rate, time to first recurrence, progression rate
      and complications. Twenty patients were enrolled and included in the analysis.
      Median follow-up was 15.2 months. Fifty-five percent (11 patients) developed
      disease recurrence. Mean time to the first recurrence was 3.5 months and 45%
      (five patients) of recurring patients had disease progression. Overall, treatment
      was well tolerated. Urinary symptoms represented the primary adverse events. The
      role of gemcitabine used as second-line treatment in high-risk BCG-refractory
      NMIBC patients who refused or were unsuitable for radical cystectomy remains to
      be defined. Further clinical research in this area is needed.

PMID- 19858711
TI  - A case of nocardiasis complicated with meningitis in a patient with immune
      thrombocytopenic purpura.
AB  - Nocardia infection is a well recognized complication of the immunocompromised
      hosts. It is mostly a primary pulmonary infection, which may disseminate to other
      organs. The central nervous system (CNS) involvement of nocardiosis is usually
      manifested as brain abscesses. We report a 25-year-old male patient who presented
      with nocardial pneumonia and meningitis without brain abscess. He was diagnosed
      as immune thrombocytopenic purpura and methyl prednisolone was started 5 weeks
      previously. Nocardia spp. was obtained from his cerebrospinal fluid culture, but
      he died at the 7th day of intensive care. Nocardia meningitis is a rare
      manifestation of systemic disease. Nocardia meningitis should be considered in
      the differential diagnosis of meningitis with the coexisting nodular pulmonary
      lesions in the immunocompromised patient and medications other than co
      trimoxazole may be required.

PMID- 19858712
TI  - Appropriate hospital management of adult immune thrombocytopenic purpura patients
      in major Italian institutions in 2000-2002: a retrospective analysis.
AB  - The treatment of immune thrombocytopenic purpura (ITP) still offers challenges to
      clinicians and health professional organizations, despite recommendations
      provided by international guidelines. In order to improve the care of patients
      with ITP, it is useful to understand how often such patients receive appropriate
      treatment and if common errors occur that could be avoided. We retrospectively
      analyzed all the clinical records between 1 January, 2000 and 31 December, 2002
      of patients receiving an ICD-9-CM diagnosis code of 287.3 in three hospitals in
      northern Italy. We examined whether management strategies of adult men and
      nonpregnant women with ITP were consistent or not with the guidelines provided by
      the American Society of Hematology. The ITP diagnosis was confirmed in 120 of 169
      patients (71%). Reasons for admission were: medical treatment for ITP (51.7%),
      medical or surgical treatment of ITP-associated disorders (30.8%), elective
      splenectomy (15.8%) and diagnosis or observation of ITP (1.7%). Hospital
      admission resulted appropriate in 78.1% of cases. Therapeutic interventions were
      appropriate in 100% of cases for glucocorticoid treatment, 86.4% for splenectomy,
      47.7% for high-dose immunoglobulins, 40.9% for prophylaxis against bleeding
      before splenectomy, 33.3% for high-dose glucocorticoid treatment, and 19% for
      prophylaxis against bacterial infections before splenectomy. Platelet
      transfusions as treatment for bleeding were appropriate in only 20% of cases.
      Confirming the usefulness of the American guidelines for ITP, our data suggest
      that there are important areas of inappropriate management of the disease, which
      could be corrected by adopting quality improvement programs and studies.

PMID- 19858713
TI  - Gender differences in coronary plaque composition by coronary computed tomography
      angiography.
AB  - BACKGROUND: Coronary computed tomography angiography allows the differentiation
      of non-calcified (NCAP), calcified (CAP), and mixed coronary artery plaques
      (MCAP). Although males are thought to have a higher prevalence of atherosclerosis
      for a given age, there are currently few data regarding age-adjusted sex
      differences in plaque morphology and composition. METHODS: We studied 1015
      consecutive asymptomatic South Korean patients (49+/-10 years, 64% men) who
      underwent 64-slice coronary computed tomography angiography during a routine
      health evaluation. Coronary plaque characteristics were analyzed on a per-segment
      basis according to the modified AHA classification. Plaques with more than 50%
      calcified tissue were classified as CAP, plaques with less than 50% calcified
      tissue were classified as MCAP, and plaques without calcium were classified as
      NCAP. Multiple regression analysis was used to describe the cross-sectional
      association between sex and plaque-type burden (>or=2 affected segments) after
      adjustment for age and other cardiovascular risk factors. RESULTS: There was a
      greater prevalence of coronary plaque among men (13 vs. 4%, P<0.001). Males were
      more likely to have an increased burden of CAP (4 vs. 1%, P = 0.01) and MCAP (5
      vs. 1%, P<0.001), whereas the burden of NCAP was similar across sex (2 vs. 1%, P
      = 0.28). After multivariable adjustment, men have six to seven times greater odds
      of having an increased burden of CAP and MCAP, whereas no sex difference was
      observed in the burden of NCAP. CONCLUSION: In this population of asymptomatic
      middle-aged Korean individuals, males had a significantly greater burden of MCAP
      and CAP. Future studies will determine whether these differences contribute to
      the accelerated cardiovascular risk observed in men.

PMID- 19858714
TI  - Evidence for airway remodeling in chronic asthma.
AB  - PURPOSE OF REVIEW: This review focuses on recent findings in relation to
      potential functional consequences of structural changes in the asthmatic airway.
      RECENT FINDINGS: Increases in smooth muscle mass have been shown to be an early
      finding in childhood asthma, related to clinical severity and predictive of
      greater airflow obstruction. Both hyperplasia and hypertrophy contribute to the
      increase in smooth muscle mass. A phenotypic shift in the epithelium of asthmatic
      airways related to stress and injury is suggested by recent data, with likely
      direct transformation of epithelial cells into mesenchymal cells. Fibrocyte in
      migration from the vasculature may be an additional source of increased smooth
      muscle mass. The increased smooth muscle may contribute to neovascularization via
      vascular endothelial growth factor. Computed tomography studies continue to show
      some correlations between wall thickness and airway physiology. Exacerbations are
      predictive of greater lung function decline and hence remodeling. SUMMARY: On
      balance, recent evidence continues to show that structural changes contribute to
      asthma persistence, airflow obstruction, lung function decline, and clinical
      severity, though there is increased recognition of the heterogeneity of asthma
      and in some phenotypes inflammatory cell influx or vascular effects may be more
      important than structural effects.

PMID- 19858715
TI  - DNA double strand break repair defects, primary immunodeficiency disorders, and
      'radiosensitivity'.
AB  - PURPOSE OF REVIEW: It is important to assess 'radiosensitivity' in patients
      suspected of immunodeficiency because underlying DNA double strand break (DSB)
      repair defects have considerable impact on V(D)J recombination, class switching
      and lymphocyte maturation, leading to increased infections and cancer risk. In
      addition, the phenotype of 'radiosensitivity' may identify patients with
      increased toxicity to radiation and chemotherapeutic agents and could impact upon
      their preparation for stem cell transplantation. To date, the gold standard for
      evaluating 'radiosensitivity' has been the colony-survival assay (CSA), which
      reflects the efficiency of DNA repair of DSBs as it impacts upon replication and
      cell survival. Other methods measure other aspects of DNA repair; however, their
      limited specificity often leads to false negatives for predicting
      'radiosensitivity', especially clinical radiosensitivity. Lastly, clinical
      awareness of an overarching syndrome of DSB repair disorders, XCIND, could help
      to raise diagnostic levels of suspicion and, thereby, identify additional
      patients with new forms of immunodeficiency, cancer susceptibility and
      radiosensitivity. RECENT FINDINGS: Within the past year, three new
      radiosensitivity disorders of DSB repair have been described, involving
      deficiencies of RNF168, RAD50, and DNA-PKcs. These are truly translational
      advances because they validate laboratory models and allow new patients to be
      identified. SUMMARY: Recognizing compromised genome stability is important but
      difficult. We review the evidence for correlations between DSB repair, abnormal
      colony formation, clinical radiosensitivity and other laboratory methods.

PMID- 19858716
TI  - Glycemic control during cardiac surgery: a moving target?

PMID- 19858717
TI  - Respiratory complications after oesophageal surgery.
AB  - PURPOSE OF REVIEW: The most frequent complications of oesophageal surgery are
      respiratory and these are associated with increased critical care stay, hospital
      stay and mortality. This review focuses on the risk factors associated with the
      development of respiratory complications after oesophageal surgery. RECENT
      FINDINGS: An acceptable operative mortality, increased and improved quality of
      life can be gained in appropriately selected patients. When induction therapy is
      scheduled, smoking cessation is advised. The preoperative treatment of airway
      pathogens can reduce postoperative complications and this may be particularly
      relevant in patients who have received induction chemoradiotherapy. Nonrandomized
      studies suggest that thoracic epidural analgesia improves outcome. Minimally
      invasive surgery is increasingly used and appears safe but direct comparisons to
      open surgery in terms of respiratory complications are awaited. Few randomized
      studies are available to guide anaesthetic management but anaesthetists should
      aim to avoid hypoxaemia, hypotension, aspiration and limit blood and fluid
      administration. Postoperative aspiration is common and steps to reduce it are
      recommended. SUMMARY: The multifactorial nature of respiratory complications
      after oesophageal surgery may mean that a number of interventions are needed to
      have a detectable influence on outcome, much like a care bundle strategy.

PMID- 19858718
TI  - Propranolol treatment for infantile hemangiomas.
AB  - PURPOSE OF REVIEW: Infantile hemangiomas are the most common benign tumors of
      infancy and the majority of them occur in the head and neck. Recent literature
      has described propranolol for the treatment of these vascular tumors. RECENT
      FINDINGS: Propranolol was serendipitously found to induce early involution in
      hemangiomas even during the proliferative phase of the hemangioma cycle. First
      reported in June 2008, and presented at the International Society for the Study
      of Vascular Anomalies meeting in Boston that same month, propranolol has stirred
      much interest in the physicians who treat these types of lesions. Early case
      report data are now appearing in the literature, and are verifying the findings
      of the initial studies as an effective treatment for hemangiomas. Our institution
      has the privilege of maintaining a high volume vascular center and we have begun
      treating patients with problematic hemangiomas with propranolol as well. The
      present article will briefly review the literature and give some of our
      preliminary experience with the drug. SUMMARY: Research regarding propranolol is
      in its infancy but, should the initial results and safety record be borne out, it
      is likely to revolutionize how we manage infantile hemangiomas.

PMID- 19858719
TI  - Botulinum toxin in the treatment of vocal fold nodules.
AB  - PURPOSE OF REVIEW: Promising new techniques in the management of vocal fold
      nodules have been developed in the past 2 years. Simultaneously, the therapeutic
      use of botulinum toxin has rapidly expanded. This review explores the use of
      botulinum toxin in treatment of vocal nodules and summarizes current therapeutic
      concepts. RECENT FINDINGS: New microsurgical instruments and techniques,
      refinements in laser technology, radiosurgical excision and steroid intralesional
      injections are all promising new techniques in the management of vocal nodules.
      Botulinum toxin-induced 'voice rest' is a new technique we have employed in
      patients with recalcitrant nodules. Successful resolution of nodules is possible
      with this technique, without the risk of vocal fold scarring inherent in
      dissection/excision techniques. Botulinum toxin usage is exponentially
      increasing, and large-scale, long-term studies demonstrate its safety profile.
      SUMMARY: Targeted vocal fold temporary paralysis induced by botulinum toxin
      injection is a new, well tolerated and efficacious treatment in patients with
      persistent vocal fold nodules.

PMID- 19858720
TI  - Bilateral and unilateral cochlear implant users compared on speech perception in
      noise.
AB  - OBJECTIVE: Compare speech performance in noise with matched bilateral cochlear
      implant (CICI) and unilateral cochlear implant (CI only) users. DESIGN: Thirty
      CICI and 30 CI-only subjects were tested on a battery of speech perception tests
      in noise that use an eight-loudspeaker array. RESULTS: On average, CICI subject's
      performance with speech in noise was significantly better than the CI-only
      subjects. CONCLUSION: The CICI group showed significantly better performance on
      speech perception in noise compared with the CI-only subjects, supporting the
      hypothesis that CICI is more beneficial than CI only.

PMID- 19858721
TI  - Wideband reflectance in normal Caucasian and Chinese school-aged children and in
      children with otitis media with effusion.
AB  - OBJECTIVES: Wideband reflectance (WBR) is a middle ear analysis technique that
      quantifies frequency-specific sound conduction over a wide range of frequencies.
      One shortcoming of WBR is that there is limited normative data, particularly for
      pediatric populations and children with middle ear pathology. The goals of this
      study were to establish normative WBR data for early school-aged children; to
      determine whether WBR differs significantly between Caucasian and Chinese
      children, male and female children, and children and adults (experiment 1); and
      to compare the normative pediatric WBR data with the WBR data obtained from
      children with abnormal middle ear conditions (experiment 2). DESIGN: WBR was
      measured from 78 children with normal middle ear status with an average age of
      6.15 yrs and 64 children with abnormal middle ear status with an average age of
      6.34 yrs. Control group subjects and subjects without previously diagnosed middle
      ear pathology were recruited from eight elementary schools in the Greater
      Vancouver Area. Subjects with known middle ear pathology were recruited through
      the British Columbia Children's Hospital Otolaryngology department. Middle ear
      effusion (MEE) was identified in one of the two ways. In the British Columbia
      Children's Hospital group, MEE was diagnosed by a pediatric otolaryngologist
      (OTL) using pneumatic otoscopy and video otomicroscopy. These cases (21 ears)
      were classified as OTL confirmed. Subjects who were assessed through screenings
      at their elementary schools and suspected to have MEE based on audiological test
      battery results including elevated air conduction thresholds, flat low- and high
      frequency tympanograms, and absent transient-evoked otoacoustic emissions were
      classified as not OTL confirmed (21 ears). Data were statistically analyzed for
      effects of gender, ethnicity (Caucasian versus Chinese), age (child versus
      adult), and middle ear condition. WBR equipment used for this study was from
      Mimosa Acoustics (RMS-system, version 4.03). Data were averaged in one-third
      octave bands collected from 248 frequencies ranging from 211 to 6000 Hz. RESULTS:
      Control group subject data (experiment 1) revealed no effects of gender or ear,
      and their interactions with frequency were not significant. There was a
      significant interaction between ethnicity (Caucasian versus Chinese) and
      frequency. Chinese children had lower energy reflectance (ER) values over the mid
      frequency range. ER was significantly different between pediatric data and
      previously collected adult data. Diseased group ER was significantly different
      among all four middle ear conditions (normal, mild negative middle ear pressure,
      severe negative middle ear pressure, and MEE) (experiment 2). The overall test
      performance of ER was objectively evaluated using receiver operating
      characteristic (ROC) curve analyses; it was compared across frequencies averaged
      in one-third octave bands. Statistical comparison of the area under ROC (AUROC)
      plots revealed that ER above 800 Hz (except for ER at 6300 Hz) had better test
      performance in distinguishing normal middle ear status from MEE compared with ER
      at 630 and 800 Hz. Although not statistically different from other frequencies
      between 800 and 5000 Hz, ER at 1250 Hz had the largest AUROC curve (sensitivity
      of 96% and specificity of 95%) and was selected for further analysis. Comparison
      of AUROC curves between WBR at 1250 Hz and static admittance at 226-Hz probe tone
      frequency revealed significantly better test performance for WBR in
      distinguishing between healthy ears and MEE. CONCLUSIONS: A preliminary set of
      normative ER data have been generated for a pediatric population between the ages
      of 5 and 7 yrs, which were significantly different from previously gathered
      normative adult ER data. In this study, pediatric normative data were warranted
      for testing children, but ethnic-specific norms were not required to detect
      middle ear pathology and changes in middle ear status. WBR shows promise as a
      clinical diagnostic tool for measuring the mechanoacoustic properties of the
      middle ear and the changes that result in the presence of negative middle ear
      pressure or MEE.

PMID- 19858722
TI  - Bimodal hearing benefit for speech recognition with competing voice in cochlear
      implant subject with normal hearing in contralateral ear.
AB  - OBJECTIVES: This project assessed electroacoustic benefit for speech recognition
      with a competing talker. DESIGN: Using a cochlear implant subject with normal
      hearing in the contralateral ear, the contribution of low-pass and high-pass
      natural sound to speech recognition was systematically measured. RESULTS: High
      frequency sound did not improve performance, but low-frequency sound did, even
      when unintelligible and limited to frequencies below 150 Hz. CONCLUSIONS: The low
      frequency sound assists separation of the two talkers, presumably using the
      fundamental frequency cue. Extrapolating this finding to regular cochlear implant
      users may suggest that using a hearing aid on the contralateral ear will improve
      performance, even with limited residual hearing.

PMID- 19858723
TI  - Alleged intraoperative awareness: a report of two cases.

PMID- 19858724
TI  - Haemodynamic consequences of mild therapeutic hypothermia after cardiac arrest.
AB  - BACKGROUND AND OBJECTIVE: Mild therapeutic hypothermia (MTH) is used after out-of
      hospital cardiac arrest (OHCA) to minimize cerebral damage. Induced hypothermia
      may further interfere with cardiac function and influence haemodynamics after
      OHCA. METHODS: This was a prospective study of haemodynamic variables in 50
      consecutive patients with OHCA treated with MTH. Patients were cooled to a core
      body temperature of 32.5 degrees C for 24 h. Induction and maintenance of cooling
      was accomplished via infusion of 2 l of cold isotonic saline (4 degrees C) and a
      cooling blanket. Rewarming was performed to 36 degrees C at a rate of 0.3 degrees
      C per hour. Haemodynamic data were analysed and compared in individual patients
      during different temperature phases. RESULTS: Heart rate dropped from a mean of
      85 to 60 beats per min (P=0.001) during hypothermia. Mean arterial pressure
      dropped from 79 to 72 mmHg, despite a rise in vasopressors and inotropes. Lactate
      levels were elevated throughout the induction (mean+/-SD) and maintenance phase
      (mean+/-SD); however, this did not correlate with a decrease in SVO2. Pulmonary
      artery pressures decreased during induction of hypothermia despite rapid
      infusion. CONCLUSION: MTH after OHCA lowered the heart rate. Despite induction of
      hypothermia with cold fluids, filling pressures decreased. Lower mean arterial
      pressure and cardiac output were observed during MTH, without deleterious effect
      on ScVO2. Lactate levels were elevated during MTH; however, levels did not
      correlate with outcome. Although the need for vasopressors and inotropes
      increases, this hypothermia-induced metabolic beta-blocker-like effect seems to
      have no negative effect on oxygen consumption and only temporarily affects
      anaerobic metabolism. No association of haemodynamic changes during MTH with
      outcome was found.

PMID- 19858725
TI  - Contemporary predictors of coronary artery disease in patients referred for
      angiography.
AB  - AIMS: Risk stratification is often used to determine the need and priority for
      coronary angiography. We investigated the contemporary value of Framingham and
      SCORE risk models, individual risk factors, B-type natriuretic peptide and high
      sensitivity C-reactive protein (hs-CRP) in the current era of intensive risk
      management. METHODS AND RESULTS: Coronary artery disease (CAD) was obstructive
      (>or=50% stenosis) in 328 of 539 patients referred for elective diagnostic
      coronary angiography (61%). Lower rates of smoking, more exercise and lower
      cholesterol were noted in those with angiographic CAD, compatible with risk
      factor modification in these patients. Framingham and SCORE were associated with
      CAD both in patients with and without prior cardiovascular disease (CVD). In
      multivariate analysis only age, male sex, diabetes, chest pain and prior CVD were
      independent predictors of CAD; odds ratio 1.74 per 10 years (95% confidence
      interval: 1.34-2.27), 5.48 (3.36-8.92), 2.57 (1.44-4.60), 1.69 (1.02-2.81) and
      2.61 (1.65-4.12), respectively. Classification of disease was not improved by B
      type natriuretic peptide or hs-CRP when added to conventional risk factors,
      although the latter seems to have value in patients without earlier CVD and low
      density lipoprotein-cholesterol of less than 3.4 mmol/l; the adjusted odds ratio
      for hs-CRP >or=2 mg/l in this sub-group was 2.49 (1.12-5.51, P=0.024).
      CONCLUSION: Framingham and SCORE risk models can be used in clinical practice to
      predict angiographic coronary disease although risk factor modification limits
      the predictive value of smoking, blood pressure, lipid profiles and cardiac
      biomarkers.

PMID- 19858726
TI  - Long-term survival and cost analysis of an annual Barrett's surveillance
      programme.
AB  - OBJECTIVES: Surveillance endoscopy aims to identify progression to high-grade
      dysplasia (HGD) or oesophageal adenocarcinoma (OA) at an early stage in patients
      with Barrett's metaplasia (BM). There are variations in surveillance practice,
      clinical outcomes and economic analyses. The study examined long-term survival
      and financial impact in patients undergoing annual surveillance of BM. METHODS:
      Patients with BM and considered fit for curative treatment between January 1994
      and July 2001 were studied. Surveillance was scheduled as annual endoscopy with
      quadrantic biopsies every 2 cm. Financial analysis was based on standard National
      Health Service costs to death or follow-up to 5 years. Comparison was made with
      patients presenting with OA over the same time period. RESULTS: Three hundred and
      two patients were identified with BM. Minimum follow-up was 5 years with a total
      follow-up of 654 patient-years. Two patients developed HGD and six OA. Median
      time between last nondysplastic biopsy and development of OA or HGD was 16 months
      (range 9-55). Five underwent potentially curative treatment. The remaining
      patients were unfit (n=1), refused surgery (n=1) or had metastatic disease (n=1).
      Four of five treated patients survived up to 5 years. The total cost of the
      surveillance programme including subsequent surgical or palliative treatment was
      euro240 682, euro30 085 per patient who progressed and for the prevalent cancer
      group (n=74) euro630 480 or euro8520 per patient. Only two patients in this group
      survived beyond 5 years. The additional cost of surveillance was euro4493 per
      life year gained. CONCLUSION: A surveillance programme leads to improved 5-year
      survival. It is cost-effective compared with dealing with unselected patients.

PMID- 19858727
TI  - Disease progression from chronic hepatitis C to cirrhosis and hepatocellular
      carcinoma is associated with repression of interferon regulatory factor-1.
AB  - BACKGROUND/AIM: Infection with hepatitis C virus (HCV) frequently results in a
      persistent infection, suggesting that it has evolved efficient mechanism(s) for
      blocking the host cell's innate antiviral response. The immune response to virus
      infection results in activation or direct induction of the interferon regulatory
      factors (IRFs), which are a family of proteins involved in the regulation of
      interferon (IFN) and IFN inducible genes. IRF-3 and IRF-7 have been shown to play
      an essential role in virus-dependent signaling, whereas IRF-1 is critical for
      proper IFN-dependent gene expression. This study has been performed to show the
      expression profile of IRF-1, IRF-3, and IRF-7 in Egyptian patients with HCV
      related liver diseases and hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      This study included 90 patients, who were positive for HCV infection by reverse
      transcription PCR, divided into three groups: group I (Gr I) included 30 patients
      with chronic hepatitis C, group II (Gr II) included 30 patients with liver
      cirrhosis in addition to group III (Gr III) of 30 patients with HCC. Reverse
      transcription PCR analysis was performed to determine the expression profile of
      IRF-1, IRF-3, and IRF-7 genes extracted from the peripheral blood mononuclear
      cells of those patients. RESULTS: IRF-1expression was significantly higher
      (P<0.001) in patients of Gr I (86.6%) compared with those in Gr II (46.7%) and Gr
      III (36.7%), whereas IRF-3 expression was significantly higher (P<0.005) among
      patients of Gr II (73.3%) in comparison with that in Gr I (50%) and Gr III
      (36.7%). In contrast, although expression of IRF-7 was higher in Gr II than in
      the other groups, there was no statistically significant difference (P > 0.05).
      CONCLUSION: Alterations in IRFs expression might be considered as markers
      associated with a higher risk of cirrhosis in patients with chronic HCV
      infection. Expression of IRF-1 and IRF-3 were more prevalent in patients with
      chronic HCV and cirrhosis, respectively, in comparison with HCC patients. Thus,
      IRF-1 could be nominated as one of the tumor suppressor factors and could aid in
      the early detection of HCC.

PMID- 19858728
TI  - High-resolution steady state magnetic resonance angiography of the carotid
      arteries: are intravascular agents necessary?: feasibility and preliminary
      experience with gadobenate dimeglumine.
AB  - PURPOSE: To prospectively evaluate the potential of gadobenate dimeglumine for
      high-resolution steady-state (SS) contrast-enhanced magnetic resonance
      angiography (CE-MRA) of the carotid arteries as an adjunct to conventional first
      pass (FP) MRA, with computed tomography angiography (CTA) and digital subtraction
      angiography (DSA) as reference. MATERIALS AND METHODS: Institutional ethics
      committee approval and written informed consent were obtained. Forty consecutive
      patients underwent conventional FP MRA with 15 mL gadobenate dimeglumine, using a
      conventional 3D FLASH sequence (14 sec acquisition time). Immediately afterward,
      SS images were obtained using a high resolution coronal 3D FLASH sequence (240
      sec acquisition time). All patients also underwent CTA and conventional DSA
      within 8 +/- 3 days. Three experienced radiologists assessed FP and SS image
      quality and calculated sensitivity, specificity, accuracy, and predictive values
      for stenosis grade and length, plaque morphology, and tandem lesions using DSA as
      reference. Detected stenoses were quantified and compared (Spearman rank
      correlation coefficient, [R(s)]; McNemar test) with DSA and CTA findings. Inter
      read variability was assessed using kappa (kappa) statistics. The impact of SS
      acquisitions on diagnostic confidence and patient management was assessed.
      RESULTS: MRA FP and SS image quality was excellent in 63 (78.8%) and 46 (57.5%)
      vessels, adequate in 11 (13.8%) and 20 (25.0%) vessels, and poor in 6 (7.5%) and
      14 (17.5%) vessels, respectively. Area under the curve analysis revealed no
      significant differences between MRA FP, MRA FP + SS, and CTA for the grading of
      stenoses (P = 0.838; accuracy values of 97.4%, 97.4%, and 98.7%, respectively).
      Greater accuracy (P < 0.001) was noted for FP + SS images over FP images alone
      for the assessment of plaque morphology (96.1% for FP + SS images vs. 83.3% for
      FP). Increased diagnostic confidence was noted for 49 (61.3%) vessels because of
      additional SS images whereas an impact on final diagnosis was noted in 8 (10%)
      cases. Good correlation was noted between SS image quality and impact on final
      diagnosis (R(s) = 0.7; P < 0.0001). CONCLUSION: SS imaging of the carotid
      arteries is feasible with gadobenate dimeglumine. The increased spatial
      resolution attainable allows improved evaluation of stenoses and plaque
      irregularity, yielding comparable diagnostic performance to that of CTA and DSA.

PMID- 19858729
TI  - Flow targeted 3D steady-state free-precession coronary MR angiography: comparison
      of three different imaging approaches.
AB  - PURPOSE: To compare 3 different flow targeted magnetization preparation
      strategies for coronary MR angiography (cMRA), which allow selective
      visualization of the vessel lumen. MATERIAL AND METHODS: The right coronary
      artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan
      ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D
      radial steady-state free-precession (SSFP) cMRA sequence with 3 different
      magnetization preparation schemes was performed referred to as projection SSFP
      (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP
      (double-inversion preparation, selective labeling of the aorta, 1 data set), and
      inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1
      data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast
      to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel
      length and vessel sharpness were analyzed. RESULTS: All cMRA sequences were
      successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP
      allowed for selective visualization of the coronary arteries with excellent
      background suppression. Scan time was doubled in projection SSFP because of the
      need for subtraction of 2 data sets. In inflow SSFP, background suppression was
      limited to the tissue included in the inversion volume. Projection SSFP
      (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7)
      and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat):
      24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn
      SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5;
      P < 0.05 for both). Longest visible vessel length was found with projection SSFP
      (79.5 mm +/- 18.9; P < 0.05 vs. LoReIn) whereas vessel sharpness was best in
      inflow SSFP (68.2% +/- 4.5%; P < 0.05 vs. LoReIn). Consistently good image
      quality was achieved using inflow SSFP likely because of the simple planning
      procedure and short scanning time. CONCLUSION: Three flow targeted cMRA
      approaches are presented, which provide selective visualization of the coronary
      vessel lumen and in addition blood flow information without the need of contrast
      agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness
      and may prove useful as a fast and efficient approach for assessing proximal and
      mid vessel coronary blood flow, whereas requiring less planning skills than
      projection SSFP or LoReIn SSFP.

PMID- 19858730
TI  - Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in
      pediatric patients.
AB  - OBJECTIVES: This clinical study investigated the pharmacokinetics and safety of
      gadobutrol, a magnetic resonance (MR) imaging extracellular contrast agent, in
      pediatric patients aged 2 to 17 years. MATERIALS AND METHODS: In this open-label,
      multicenter study, patients scheduled for routine contrast-enhanced MR imaging of
      the brain, spine, liver or kidney, or MR angiography received a single
      intravenous injection of gadobutrol (0.1 mmol/kg/0.1 mL/kg). Patients were
      stratified by age groups (2-6, 7-11, and 12-17 years). Blood and urine samples
      were collected at prespecified time points and analyzed for gadolinium
      concentrations. Plasma data were evaluated by means of a nonlinear mixed effects
      model, and urine data were analyzed using descriptive statistics. In addition,
      the safety of gadobutrol was evaluated. RESULTS: A total of 130 patients (2-6
      years, n = 45; 7-11 years, n = 39; 12-17 years, n = 46) were included in the
      final population pharmacokinetic analysis. Gadobutrol pharmacokinetics in
      children aged 2 to 17 years were adequately described by an open 2-compartment
      model with elimination from the central compartment. The median estimates (2.5th
      percentile, 97.5th percentile) of body weight-normalized total body clearance
      (L/h/kg) per age group were 0.10 (0.05, 0.17) for all ages, 0.13 (0.09, 0.17) in
      the 2 to 6 year age group, 0.10 (0.05, 0.17) in the 7 to 11 year age group and
      0.09 (0.05, 0.10) in the 12 to 17 year age group. The body weight-normalized
      median estimates of total volume of distribution (L/kg) were 0.20 (0.12, 0.28)
      for all ages, 0.24 (0.20, 0.28) in the 2 to 6 year age group, 0.19 (0.14, 0.23)
      in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age
      group. Median gadolinium plasma concentrations at 20 minutes postinjection were
      simulated using the population pharmacokinetic model and ranged from 414 (13 kg
      subject) to 518 micromol/L (65 kg subject). Body weight was identified as the
      major covariate influencing the pharmacokinetic parameters of total body
      clearance and central volume of distribution. Age was not found to be an
      additional independent parameter. The median amount of renally excreted
      gadolinium was 77.0% of the administered dose within 6 hours postinjection,
      indicating that gadobutrol was renally excreted in this pediatric population aged
      2 to 17 years. Gadobutrol was well tolerated, with drug-related adverse events of
      mild intensity reported for 8 (5.8%) of 138 patients. CONCLUSIONS: Observed
      differences in pharmacokinetics were attributed to body weight, with no
      additional independent effect of age. Thus, no dose adjustment from the standard
      dose of gadobutrol in adults based on body weight (0.1 mmol/kg) is necessary in
      pediatric patients aged 2 to 17 years. Gadobutrol was safe and well tolerated in
      the pediatric population in this study.

PMID- 19858731
TI  - Contemporary evidence of coronary atherosclerotic disease and myocardial bridge
      on left anterior descending artery in a patient with a nonobstructive
      hypertrophic cardiomyopathy.

PMID- 19858732
TI  - Evolution of renal function during and after an episode of cardiac
      decompensation: results from the Italian survey on acute heart failure.
AB  - BACKGROUND: Renal dysfunction is frequently associated with heart failure and
      strongly influences the outcome of heart failure patients. Although recommended
      pharmacological interventions for heart failure may contribute to the development
      of, or worsen renal dysfunction, their relations with renal function have not
      been fully explored in an unselected community population. METHODS AND AIM: We
      studied 1008 patients recruited in the Italian survey on acute heart failure to
      assess the prevalence, the prognostic role of renal function and the relations
      between the changes in renal function and the pharmacological interventions
      during hospitalization and at 6-month follow-up. Patients were categorized using
      the National Kidney Foundation cut-offs for degree of renal function measured by
      the glomerular filtration rate. RESULTS: Moderate-to-severe renal dysfunction was
      diagnosed in 59% of patients at hospital admission and 61% at discharge. These
      patients were older and had a higher prevalence of diabetes, anemia, history of
      hypertension, myocardial infarction and hospitalization for heart failure than
      those with normal or mildy impaired renal function. At admission the former were
      treated more frequently with diuretics, angiotensin converting enzyme-inhibitor
      (ACEi) or angiotensin receptor blockers (ARBs) than the latter. Diuretics were
      given at higher dose and for a longer time during the hospital stay while beta
      blockers, digoxin, antialdosterone agents, ACEi and ARBs were given less
      frequently in patients who had moderate-to-severe renal dysfunction than those
      who did not. High-dose diuretic treatment, inability to start or maintain beta
      blockers during hospital stay and the nonprescription of ACEi/ARBs at discharge
      emerged, by multivariate analysis, as predictors of death at 6-month follow-up
      (mortality rate = 14%), independent of the persistence of moderate-to-severe
      renal dysfunction over time, anemia, male sex and history of heart failure.
      CONCLUSIONS: In acute heart failure, renal dysfunction is frequent and impacts
      prognosis. In this setting, the pharmacological interventions are significantly
      associated with changes in renal function and 6-month mortality.

PMID- 19858733
TI  - Olive oil and cardiovascular health.
AB  - The Mediterranean diet, in which olive oil is the primary source of fat, is
      associated with a low mortality for cardiovascular disease. Data concerning olive
      oil consumption and primary end points for cardiovascular disease are scarce.
      However, a large body of knowledge exists providing evidence of the benefits of
      olive oil consumption on secondary end points for the disease. Besides the
      classical benefits on the lipid profile provided by olive oil consumption
      compared with that of saturated fat, a broad spectrum of benefits on
      cardiovascular risk factors is now emerging associated with olive oil
      consumption. We review the state of the art concerning the knowledge of the most
      important biological and clinical effects related to olive oil and its minor
      components. The recent advances in human nutrigenomics associated with olive oil
      consumption will also be assessed. The wide range of benefits associated with
      olive oil consumption could contribute to explaining the low rate of
      cardiovascular mortality found in southern European-Mediterranean countries, in
      comparison with other westernized countries, despite a high prevalence of
      coronary heart disease risk factors.

PMID- 19858734
TI  - Cardiovascular effects of oxytocin infusion in a porcine model of myocardial
      infarct.
AB  - The effects of oxytocin (OT) on cardiovascular endpoints were assessed in a
      myocardial infarct (MI) model. OT (10 ng.kg(-1).hour(-1)) or saline infusion was
      initiated at reperfusion (D0) or 8 days (D8) after MI. Our hypothesis was that OT
      administration to individuals with a low pretreatment OT levels (PTOT) may be
      beneficial, whereas individuals with an elevated PTOT would be prone to adverse
      effects. Starting OT on D0 reduced left ventricular fraction shortening evaluated
      8 days post MI and had no effect on infarct size. OT initiated on D8 in animals
      with high PTOT decreased ejection fraction (EF) and increased left ventricular
      end-systolic diameter at 28 days post MI but had no significant effects on EF and
      left ventricular end-systolic diameter in low PTOT animals. OT infusion reduced
      OT receptor protein expression in high PTOT animals but not in low PTOT animals.
      Among placebo-treated individuals, low PTOT presented a trend toward reduced EF
      and larger infarct size compared with high PTOT. MI areas of fibrosis presented
      lower Annexin V expression compared with MI with cardiomyocyte predominance.
      Pretreatment endogenous OT levels and timing of OT administration post MI seem to
      impact outcome in this porcine model, and further investigations are warranted to
      define potential role of OT in cardiac regenerative therapy.

PMID- 19858735
TI  - Long-term effects of B-type natriuretic peptide infusion after acute myocardial
      infarction in a rat model.
AB  - INTRODUCTION: The effects of exogenous B-type natriuretic peptide (BNP) on
      postmyocardial infarction (MI) are not known. We tested the hypothesis that in
      vivo infusion of BNP would improve cardiac function and affect left ventricular
      (LV) remodeling in an experimental model of MI. METHODS: MI was induced by
      coronary ligation in rats and confirmed by echocardiography. 19 rats were
      randomized to 1 of 3 groups: sham (n = 7), MI + saline (n = 5), MI + BNP (400
      ng.kg(-1).minute(-1)) (n = 7). Infusions were delivered for 7 days via venous
      catheters tunneled to an infusion pump. Rats were followed for 8 weeks.
      Echocardiography, hemodynamics, histology, and in vivo and ex vivo pressure
      volume relationships were examined. RESULTS: LV systolic pressure, LV dP/dtmax,
      and infarct size improved with BNP treatment versus control MI group (132 +/- 4
      vs.110 +/- 2 mm Hg, 8097 +/- 317 vs. 5816 +/- 378 mm Hg/s, 19.3% +/- 1.6% vs.
      23.3% +/- 1.9%, respectively; all P < 0.05). Ex vivo end-diastolic pressure
      volume relationship demonstrated reduced diastolic dysfunction after BNP therapy
      (P < 0.05 vs. control MI). Serum BNP levels confirmed delivery of BNP.
      CONCLUSIONS: We demonstrate beneficial effects on LV function and decreased LV
      remodeling with BNP infusion in an experimental model of acute MI.

PMID- 19858738
TI  - The role of the registered nurse in determining distal tip placement of
      peripherally inserted central catheters by chest radiograph.

PMID- 19858736
TI  - Rapid aldosterone signaling and vascular reactivity: relax or don't do it.

PMID- 19858739
TI  - 1,3-butadiene, styrene and lung cancer among synthetic rubber industry workers.
AB  - OBJECTIVE: To evaluate the association between cumulative exposure to 1,3
      butadiene (BD) or styrene (STY) and lung cancer among synthetic rubber industry
      workers. METHODS: Internal Cox regression analyses were performed both with and
      without natural logarithm transformation of exposure variables and both with and
      without the inclusion of those unexposed to monomers. RESULTS: Among women,
      analyses using untransformed BD exposure showed no trend. Analyses using natural
      logarithm-transformed BD exposure indicated a positive trend when the unexposed
      were included (P < 0.05) and an inverse trend when the unexposed were excluded (P
      < 0.05). No exposure-response trends were seen for BD among men or for STY among
      women or men. CONCLUSIONS: These results suggest that the association between BD
      and lung cancer, seen in some analyses of female employees, is not causal. STY
      did not appear to be associated with lung cancer.

PMID- 19858740
TI  - A new health promotion model for lone workers: results of the Safety & Health
      Involvement For Truckers (SHIFT) pilot study.
AB  - OBJECTIVE: This study was designed to evaluate the effectiveness of a new health
      promotion model for lone workers. METHODS: A single group pre- or posttest design
      was used to evaluate intervention effectiveness for reducing body weight and
      increasing healthful and safe behaviors. Truck drivers (n = 29) from four
      companies participated in a 6-month intervention involving a weight loss and safe
      driving competition, computer-based training, and motivational interviewing.
      RESULTS: Objectively measured body weight reduced by 7.8 lbs (DeltaSD = 11.5,
      Deltad = 0.68, P = 0.005), and survey measures showed significant reductions in
      dietary fat and sugar consumption. An objective measure of safe driving also
      showed significant improvement, and increases in exercise motivational stage and
      walking fitness approached significance. CONCLUSIONS: Results suggest that the
      new intervention model is substantially more engaging and effective with truck
      drivers than previous education-based tactics.

PMID- 19858741
TI  - The association between beliefs about low back pain and work presenteeism.
AB  - OBJECTIVE: To examine the influence of beliefs about low back pain (LBP) on
      reduced productivity at work ("presenteeism") caused by LBP. METHODS: Two
      thousand five hundred seven individuals completed the Back Beliefs Questionnaire,
      the Fear Avoidance Beliefs questionnaire (FABQ), and questions about LBP-related
      work-absence, reduced work-productivity, pain, comorbidity, and demographics.
      RESULTS: Six hundred seventy (25%) individuals were of working age, employed and
      reported current LBP. Univariate models showed beliefs were more "negative" in
      individuals with work-absence and reduced productivity (P = 0.0001). In
      multivariable analysis, controlling for confounders, "FABQwork" was a unique
      predictor of both absenteeism and presenteeism (each, P = 0.0001), though with
      small effect sizes. CONCLUSIONS: Negative beliefs about LBP are associated with
      both work absence and reduced work-productivity. Further investigations should
      examine their potential as a target for educational interventions when
      considering initiatives to reduce the socioeconomic costs of LBP.

PMID- 19858742
TI  - Mortality patterns and trends among 127,266 U.S.-based men in a petroleum
      company: update 1979-2000.
AB  - OBJECTIVE: To assess patterns and trends in mortality among men employed in U.S.
      operating segments of a petroleum company. METHODS: We defined a cohort of
      127,266 men with at least 1 day of employment during the period of 1979 through
      2000. Computerized human resources databases were the basis of the cohort
      definition as well as the source of demographic and most work history
      information. Standardized mortality ratios (SMR) and 95% confidence intervals
      (CI) were calculated for 94 causes of death, including analyses by operating
      segment and job type. RESULTS: Most SMR results are below unity. The main
      exception is mesothelioma (SMR = 1.49; 95% CI = 1.15 to 1.90), which has
      elevations three times greater than expectation among some groups of men working
      in manufacturing sites who were hired before 1960. SMRs for cancers of the blood
      and blood-forming organs are generally close to unity, whereas men in the
      chemicals segment have 17 deaths due to acute non-lymphocytic leukemia (SMR =
      1.81; 95% CI = 1.06 to 2.90), with no temporal or job type patterns. Men in the
      downstream segment have an elevation of aplastic anemia (SMR = 2.19; 95% CI =
      0.95 to 4.32), based on eight deaths. There are eight deaths from malignant
      melanoma among downstream drivers (SMR = 2.46; 95% CI = 1.06 to 4.84), and motor
      vehicle accident rates are slightly elevated among some groups of younger and
      shorter-term operators. CONCLUSIONS: This comprehensive study indicates an
      overall favorable mortality profile for this workforce. For a few elevations, the
      study helps guide decisions about future surveillance, focused studies, and other
      follow-up actions.

PMID- 19858744
TI  - Incremental employee health benefit costs, absence days, and turnover among
      employees with ADHD and among employees with children with ADHD.
AB  - OBJECTIVE: To assess employer economic burden of attention-deficit/hyperactivity
      disorder (ADHD) for employees with ADHD and employee caregivers of children with
      ADHD. METHODS: A large multi-employer database was used to compare: 1) employees
      diagnosed with ADHD versus employees without ADHD and 2) employee caregivers of
      children with ADHD versus employee caregivers of children without ADHD.
      Regression modeling compared many employer-relevant outcomes. RESULTS: The study
      found significantly higher annual health benefit costs ($6885 versus $4242),
      absence days (8.86 versus 7.16), and turnover (8.99% versus 5.26%) for employees
      with ADHD (n = 539) versus employees without ADHD (n = 93,722), respectively (all
      P < 0.01). Similar results were found for employee caregivers of children with
      ADHD. CONCLUSIONS: Employees with ADHD and those caring for children with ADHD
      are associated with a significantly higher burden in employer-relevant outcomes
      such as health benefit costs, absences, and terminations.

PMID- 19858743
TI  - A follow-up study of mortality among women in the North American synthetic rubber
      industry.
AB  - OBJECTIVE: To evaluate mortality from cancer and other diseases among 4863 women
      employed at eight North American styrene-butadiene rubber plants. Cancers of the
      lymphohematopoietic tissues, breast, and ovary were of strongest a priori
      interest. METHODS: Cause-specific standardized mortality ratios (SMRs) and 95%
      confidence intervals (CIs) were estimated. RESULTS: The observed number of deaths
      was approximately equal to that expected for leukemia (10 observed/13 expected),
      Hodgkin lymphoma (1/1.6), multiple myeloma (7/7.9), non-Hodgkin lymphoma (15/14),
      and cancers of the breast (72/74) and ovary (21/22). Ever-hourly women had more
      than expected deaths from lung (47/30, SMR = 159, CI = 117 to 211) and bladder
      (6/1.8, SMR = 332, CI = 122 to 723) cancers. Exposure-response analysis, done
      only for lung cancer, indicated no trend for butadiene or styrene. CONCLUSIONS:
      The observed excesses of lung and bladder cancers may be attributable to
      nonoccupational factors rather than to workplace exposures.

PMID- 19858745
TI  - Exposure risk assessment in an aluminium salvage plant.
AB  - INTRODUCTION: A cross-sectional study was conducted to evaluate possible nervous
      or respiratory system effects from occupational aluminium exposure. METHODOLOGY:
      Exposed workers in Al salvage plant were compared with controls. The
      investigation involved a standardized occupational and medical history and
      assessments of Al levels in ambiance, serum, and urine. This was combined with an
      evaluation of respiratory complaints, lung, and cognitive functions. RESULTS:
      Thirty workers exposed to Al were matched to 60 individuals without exposure to
      Al. Significantly higher internal doses of Al in urine were found in exposed
      workers (11.59 microg/L), when compared with the controls (4.37 microg/L). Few
      high Al atmospheric levels were obtained (0.12-10.86 mg/m3). No significant
      differences concerning respiratory or neurological symptoms prevalence between
      the two groups were reported. DISCUSSION: Chronic exposure to Al dust, at the
      levels documented in this study over the German limit values, does not induce
      measurable cognitive decline.

PMID- 19858746
TI  - Guidance for Occupational Health Services in Medical Centers.

PMID- 19858747
TI  - Long-term exposure and health-related quality of life among patients with
      occupational rhinitis.
AB  - OBJECTIVE: This article evaluates health-related quality of life (HRQoL) among
      patients with occupational rhinitis (OR), with an average of 10 years after
      diagnosis. METHODS: A cross-sectional questionnaire with general (RAND-36) and
      disease-specific (Rhinasthma) HRQoL questions was completed by 119 OR patients
      and 173 controls of the same age and locality. In addition, the patients compared
      their estimation of current occupational exposure level with that at the time of
      OR diagnosis. RESULTS: HRQoL was impaired among patients with continuing
      occupational allergen exposure in all Rhinasthma and several RAND-36 scores. The
      HRQoL among patients no longer exposed was mainly similar to that of the healthy
      controls. CONCLUSIONS: Among OR patients, continuous occupational exposure
      decreases QoL years after the diagnosis. To restore the well being of patients
      with OR, medication only is not sufficient; reduction or cessation of exposure is
      necessary.

PMID- 19858748
TI  - Reproductive history and adverse pregnancy outcomes in commercial flight crew and
      air traffic control officers in the United kingdom.
AB  - OBJECTIVE: To examine reproductive outcomes among flight crew. METHODS: Ten
      thousand two hundred five flight crew members and a control group of 2118 air
      traffic control officers completed a questionnaire in 2001 to 2004, United
      Kingdom. RESULTS: Similar proportions of flight crew and air traffic control
      officers reported having ever had difficulties in conceiving a baby. Risks of
      miscarriages and congenital malformations among pregnancies fathered by men who
      did not differ by occupation, but stillbirth risk was higher among flight crew
      (odds ratio = 2.85; 95% CI = 1.30-6.23). Among pregnancies reported by women,
      risks of miscarriage and stillbirth did not differ by occupation but risk of
      congenital malformations was higher among flight crew (odds ratio = 2.37; 95% CI
      = 0.43-13.06). CONCLUSIONS: Flight crew-related exposures were not associated
      with adverse reproductive outcomes except for possible links, based on small
      numbers, between paternal exposure and stillbirths and maternal exposure and
      congenital malformations.

PMID- 19858749
TI  - Epidemiologic studies of styrene and cancer: a review of the literature.
AB  - OBJECTIVE: To review the epidemiologic literature on styrene and cancer. METHODS:
      We reviewed studies of workers exposed to styrene in manufacturing and
      polymerization, in the reinforced plastics industry, and in styrene-butadiene
      rubber production. We also reviewed studies of workers monitored for styrene
      exposure, studies of environmental exposure, community-based case-control studies
      of lymphoma and leukemia, and studies of DNA adducts. Studies of workers in the
      reinforced plastics industry were considered more informative because of higher
      worker exposure and less confounding by other carcinogens. RESULTS: We found no
      consistent increased risk of any cancer among workers exposed to styrene. A study
      of reinforced plastic workers reported an association between average estimated
      styrene exposure and non-Hodgkin lymphoma (NHL, P = 0.05) but no trend with
      increasing duration of exposure. Other studies of styrene exposure and NHL found
      no increased risk. In two US studies of reinforced plastic workers, esophageal
      cancer mortality was increased, but these findings were generated in a background
      of multiple comparisons. Results for other cancers were unremarkable.
      CONCLUSIONS: The available epidemiologic evidence does not support a causal
      relationship between styrene exposure and any type of human cancer.

PMID- 19858750
TI  - Pelvic osteomyelitis in children.
AB  - Pelvic osteomyelitis is a rare disease that presents like many other common
      paediatric orthopaedic conditions. The diagnosis and management of the disease is
      often delayed and as a consequence this may contribute to increased morbidity in
      affected individuals. In an attempt to improve our diagnostic accuracy, 23 cases
      of pelvic osteomyelitis presenting to our tertiary referral centre between 1998
      and 2006 were reviewed. Case notes were reviewed to examine clinical,
      pathological and radiological variables attributable to pelvic osteomyelitis, as
      well as subsequent management of the disease. Pelvic osteomyelitis was diagnosed
      on the basis of a positive bone and/or magnetic resonance scan. The presentation
      was associated with a limp and a history of non-weight bearing. The patients
      presented with an average temperature of 38.4 degrees C and pathology revealed an
      average erythrocyte sedimentation rate and C-reactive protein of 61.2 and 59.1,
      respectively. A child with a clinical picture including limping, fevers and
      raised inflammatory markers should be approached with a high index of suspicion
      of pelvic osteomyelitis. Seven patients in our series required surgical
      intervention for debridement and washout. Magnetic resonance imaging performed in
      the most recent cases was found to be a useful investigation in the diagnosis and
      management of pelvic osteomyelitis.

PMID- 19858751
TI  - Alterations in speed of squat movement and the use of accommodated resistance
      among college athletes training for power.
AB  - The purpose of this study was to assess the effect of heavy/slow movements and
      variable resistance training on peak power and strength development. Forty-eight
      National Collegiate Athletic Association (NCAA) Division I athletes (age: 21.4 +/
      2.1 years, all men) were recruited for this 12-week training intervention study.
      Maximum strength and jumping power were assessed before and after the training
      program. Athletes were randomly assigned to 1 of 3 training groups: heavy
      resistance/slow movement (Slow), lighter resistance and fast movement (Fast), or
      fast movements with accommodated resistance (FACC). All training groups performed
      similar training programs comprising free weight resistance training with lower
      body compound exercises. The only difference among the training interventions was
      the speed at which subjects performed the squat exercise and the use of bands
      (Slow group: 0.2-0.4 meters/second; Fast group: 0.6-0.8 meters/second; FACC group
      trained 0.6-0.8 meters/second with the addition of accommodated resistance in the
      form of large elastic bands). Post-test data revealed a significant difference
      between power improvements between the Slow and FACC groups (p = 0.02). Percent
      increases and effect sizes (ES) demonstrated a much greater treatment effect in
      the FACC group (17.8%, ES = 1.06) with the Fast group (11.0%, ES = 0.80) adapting
      more than the Slow group (4.8%, ES = 0.28). The FACC and Slow groups improved
      strength comparatively (FACC: 9.44%, ES = 1.10; Slow: 9.59%, ES = 1.08). The Fast
      group improved strength considerably less, 3.20% with an effect size of only
      0.38. Variable resistance training with elastic bands appears to provide greater
      performance benefits with regard to peak force and peak power than heavy, slow
      resistance exercise. Sports conditioning professionals can utilize bands, and
      high-speed contractions, to increase power development.

PMID- 19858752
TI  - An examination of the relationships among myosin heavy chain isoform content,
      isometric strength, and mechanomyographic median frequency.
AB  - The purpose of the present study was to determine if the combination of isometric
      knee extension strength and mechanomyographic (MMG) median frequency (MDF) could
      be used to estimate the percent (%) myosin heavy chain (MHC) Type II isoform
      content of the vastus lateralis. Five resistance-trained (mean +/- SD age = 23.2
      +/- 3.7 years) and 5 aerobically trained (mean +/- SD age = 32.6 +/- 5.2 years)
      men volunteered to perform a 6-second isometric maximum voluntary contraction
      (MVC) of the dominant knee extensors at a joint angle of 90 degrees between the
      thigh and leg. During the isometric MVC, the surface MMG signal was detected from
      the vastus lateralis, and the MDF was calculated with the discrete Fourier
      transform. Following the isometric MVC and MMG measurements, muscle biopsies were
      taken from the vastus lateralis and analyzed for % MHC Type II isoform content.
      The results showed that neither isometric knee extension strength nor MMG MDF
      alone was significantly correlated with the % MHC Type II isoform content. The
      combination of isometric knee extension strength and MMG MDF, however, explained
      a significant proportion (i.e., 59.8%) of the variance in % MHC Type II isoform
      content, with a multiple correlation of R = 0.773 and a standard error of the
      estimate (SEE) of 15.4%. These findings indicated that a simple, time-efficient,
      and noninvasive test that simultaneously measures isometric strength and MMG MDF
      could be useful for estimating the % MHC Type II isoform content in well-trained
      men.

PMID- 19858753
TI  - The effects of creatine monohydrate supplementation with and without D-pinitol on
      resistance training adaptations.
AB  - Coingestion of D-pinitol with creatine (CR) has been reported to enhance creatine
      uptake. The purpose of this study was to evaluate whether adding D-pinitol to CR
      affects training adaptations, body composition, whole-body creatine retention,
      and/or blood safety markers when compared to CR ingestion alone after 4 weeks of
      resistance training. Twenty-four resistance trained males were randomly assigned
      in a double-blind manner to creatine + pinitol (CRP) or creatine monohydrate (CR)
      prior to beginning a supervised 4-week resistance training program. Subjects
      ingested a typical loading phase (i.e., 20 g/d-1 for 5 days) before ingesting 5
      g/d-1 the remaining 23 days. Performance measures were assessed at baseline (T0),
      week 1 (T1), and week 4 (T2) and included 1 repetition maximum (1RM) bench press
      (BP), 1RM leg press (LP), isokinetic knee extension, and a 30-second Wingate
      anaerobic capacity test. Fasting blood and body composition using dual-energy x
      ray absorptiometry (DEXA) were determined at T1 and T3. Data were analyzed by
      repeated measures analysis of variance (ANOVA). Creatine retention increased (p <
      0.001) in both groups as a result of supplementation but was not different
      between groups (p > 0.05). Significant improvements in upper- and lower-body
      strength and body composition occurred in both groups. However, significantly
      greater increases in lean mass and fat-free mass occurred in the CR group when
      compared to CRP (p <0.05). Adding D-pinitol to creatine monohydrate does not
      appear to facilitate further physiological adaptations while resistance training.
      Creatine monohydrate supplementation helps to improve strength and body
      composition while resistance training. Data from this study assist in determining
      the potential role the addition of D-pinitol to creatine may aid in facilitating
      training adaptations to exercise.

PMID- 19858754
TI  - Efficacy of dynamic muscular stabilization techniques (DMST) over conventional
      techniques in rehabilitation of chronic low back pain.
AB  - Low back pain (LBP) is a common health problems. Although it is multifactorial,
      its treatment varies considerably, including medication, physical therapy
      modalities, and exercise therapy, and each have several interventions. Despite
      their effectiveness, their head-to-head comparisons are limited. This study was
      aimed at 1 such comparison. A total of 30 hockey players, 18 to 28 years of age,
      with subacute or chronic LBP were randomly assigned equally in 2 groups. One
      group was treated with conventional treatment--a combination of 2
      electrotherapies (ultrasound and short-wave diathermy) and 1 exercise therapy
      (lumbar strengthening exercises)--and the other group was treated with dynamic
      muscular stabilization techniques (DMST), an active approach of stabilizing
      training. The results showed that both the treatments are effective in the
      management of LBP, but DMST was found to be more effective than conventional
      treatment. The walking, stand ups, climbing, and pain improved 4.7, 2.0, 1.4, and
      2.1 times, respectively, more with DMST than with conventional treatment. With
      time (days), walking, stand ups, climbing, and pain improved (correlation)
      significantly (p < 0.01) higher in DMST (r = 0.83 to 0.92) than in conventional
      treatment (r = 0.40 to 0.75), and their rate of improvement (regression beta
      coefficients) were also significantly (p < 0.01) higher in DMST (beta = -0.16 to
      0.73) than in conventional treatment (beta = -0.07 to 0.15). Subjects matching
      were perfect (p < 0.01) and test-retest reliability of all dependent variables
      was significantly (p < 0.01) high (intraclass correlation coefficient
      approximately 1). No major adverse effects were recorded in any of the patients
      in either group. This study concluded that for early recovery, DMST is more
      suitable than conventional treatment.

PMID- 19858755
TI  - Acute effect of drop jumping on throwing performance.
AB  - The purpose of the present study was to investigate the acute effect of drop
      jumping on throwing performance. Eight men and 8 women, moderately trained
      subjects with basic shot put skills, performed 3 squat underhand front shot
      throws after a short standard warm-up. Three minutes later they performed 5
      maximal consecutive drop jumps from 40 cm. Immediately after the drop jumps, they
      repeated the squat underhand front shot throws. On another day, their 6
      repetition maximum (RM) muscular strength in leg press was assessed. Muscle
      biopsies were also obtained from vastus lateralis for the determination of fiber
      type composition and fiber cross-sectional area. Throwing performance was
      significantly increased after drop jumping (8.25 +/- 1.1 m vs. 8.63 +/- 1.3 m, p
      < 0.01). The percentage of type II muscle fiber area was significantly related to
      the increase in throwing performance after drop jumping (r = 0.76, p < 0.01). The
      increase in throwing performance was significant in men (8.94 +/- 1 m vs. 9.60 +/
      0.9 m, p < 0.01) but not in women (7.56 +/- 1 m vs. 7.67 +/- 0.9 m, ns). Of
      note, the percentage of type II fiber area was higher in men than in women (M:
      66.4 +/- 13%, F: 50.2 +/- 15%, p < 0.01). Leg press strength (6RM) was moderately
      related to the increase in throwing performance after drop jumping (r = 0.50, p <
      0.05). These results suggest that drop jumping just before a throwing action
      induces an increase in performance in subjects with a high percentage of type II
      muscle fiber area and (to a lesser degree) in subjects with enhanced muscular
      strength.

PMID- 19858756
TI  - Flexible nonlinear periodization in a beginner college weight training class.
AB  - The purpose of this study was to determine the effect of a flexible nonlinear
      (FNL) periodized weight training program compared to a nonlinear (NL) periodized
      weight training program on strength and power. Sixteen beginner weight training
      students were randomly assigned to an FNL group (n = 8) or an NL group (n = 8).
      The exercise program included a combination of machines and free weights
      completed in 30 minutes, twice per week, for 12 consecutive weeks. Both groups
      were assigned the same total training volume of 3,680 repetitions and the same
      total training repetition maximum assignments of 10, 15, and 20. The FNL group,
      however, was allowed to choose which day they completed the 10, 15, or 20
      repetition workout. This was the only difference between the groups. Pre- and
      post-test measures included chest press, leg press, and standing long jump. The
      FNL group significantly improved by an average increase of 62 kg (p < 0.05),
      whereas the NL group only increased by an average of 16 kg in the leg press. The
      FNL group did not significantly differ in chest press or standing long jump
      performance when compared to the NL group. The conclusion from this study is that
      an FNL periodization program may be a highly effective method of training for
      improving leg strength. Coaches can immediately implement an FNL program by
      evaluating the readiness of an athlete immediately before his or her training
      session, then adjusting the assigned exercise intensity accordingly.

PMID- 19858757
TI  - Intrauterine cannabis exposure affects fetal growth trajectories: the Generation
      R Study.
AB  - OBJECTIVE: Cannabis is the most commonly consumed illicit drug among pregnant
      women. Intrauterine exposure to cannabis may result in risks for the developing
      fetus. The importance of intrauterine growth on subsequent psychological and
      behavioral child development has been demonstrated. This study examined the
      relation between maternal cannabis use and fetal growth until birth in a
      population-based sample. METHOD: Approximately 7,452 mothers enrolled during
      pregnancy and provided information on substance use and fetal growth. Fetal
      growth was determined using ultrasound measures in early, mid-, and late
      pregnancy. Additionally, birth weight was assessed. RESULTS: Maternal cannabis
      use during pregnancy was associated with growth restriction in mid-and late
      pregnancy and with lower birth weight. This growth reduction was most pronounced
      for fetuses exposed to continued maternal cannabis use during pregnancy. Fetal
      weight in cannabis-exposed fetuses showed a growth reduction of -14.44 g/week
      (95% confidence interval -22.94 to -5.94, p = .001) and head circumference (-0.21
      mm/week, 95% confidence interval -0.42 to 0.02, p = .07), compared with
      nonexposed fetuses. Maternal cannabis use during pregnancy resulted in more
      pronounced growth restriction than maternal tobacco use. Paternal cannabis use
      was not associated with fetal growth restriction. CONCLUSIONS: Maternal cannabis
      use, even for a short period, may be associated with several adverse fetal growth
      trajectories.

PMID- 19858758
TI  - Service use by at-risk youths after school-based suicide screening.
AB  - OBJECTIVE: We sought to examine follow-up service use by students identified at
      risk for suicidal behavior in a school-based screening program and assess
      barriers to seeking services as perceived by youths and parents. METHOD: We
      conducted a longitudinal study of 317 at-risk youths identified by a school-based
      suicide screening in six high schools in New York State. The at-risk teenagers
      and their parents were interviewed approximately 2 years after the initial screen
      to assess service use during the intervening period and identify barriers that
      may have interfered with seeking treatment. RESULTS: At the time of the
      screening, 72% of the at-risk students were not receiving any type of mental
      health service. Of these students, 51% were deemed in need of services and
      subsequently referred by us to a mental health professional. Nearly 70% followed
      through with the screening's referral recommendations. The youths and their
      parents reported perceptions about mental health problems, specifically relating
      to the need for treatment, as the primary reasons for not seeking service.
      CONCLUSIONS: Screening seems to be effective in enhancing the likelihood that
      students at risk for suicidal behavior will get into treatment. Well-developed
      and systematic planning is needed to ensure that screening and referral services
      are coordinated so as to facilitate access for youths into timely treatment.

PMID- 19858759
TI  - Characteristics of placebo responders in pediatric clinical trials of attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: Understanding placebo response is a prerequisite to improving clinical
      trial methodology. Data from placebo-controlled trials of atomoxetine in the
      treatment of children and adolescents with attention-deficit/hyperactivity
      disorder (ADHD) were analyzed to identify demographic and clinical
      characteristics that might predict placebo response in future clinical trials.
      METHOD: Data were pooled across 731 placebo-treated pediatric patients who
      participated in 10 acute, randomized, placebo-controlled trials. Responder status
      was based on empirically derived thresholds of change on the total score of the
      ADHD Rating Scale with minimal and robust response defined as 25% or greater and
      40% or greater decrease, respectively. Study design characteristics, including
      randomization ratio, dose, and titration strategy, and patient demographic and
      clinical characteristics were examined as potential predictors of placebo
      response. RESULTS: Inattentive subtype, lack of previous stimulant treatment,
      presence of comorbid tics and nonwhite ethnicity were associated with robust
      placebo response. A subset analysis of patients completing 6 weeks of treatment
      (to eliminate the effects of early dropout) identified inattentive subtype and
      lack of previous stimulant experience as significant predictors of robust placebo
      response. CONCLUSIONS: Placebo response is less likely in subjects with combined
      subtype ADHD who are not stimulant-naive. Limiting ADHD clinical trials to this
      more restricted subject group is likely to maximize treatment differences.
      However, because this is not always possible or desirable, identifying other
      methods of mitigating placebo response is essential.

PMID- 19858760
TI  - A candidate gene analysis of methylphenidate response in attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: This study examines the potential role of candidate genes in
      moderating treatment effects of methylphenidate (MPH) in attention
      deficit/hyperactivity disorder (ADHD). METHOD: Eighty-two subjects with ADHD aged
      6 to 17 years participated in a prospective, double-blind, placebo-controlled,
      multiple-dose, crossover titration trial of immediate release MPH three times
      daily. The subjects were assessed on a variety of parent and clinician ratings
      and a laboratory math test. Data reduction based on principal components analysis
      identified statistically derived efficacy and side effect outcomes. RESULTS:
      Attention-deficit/hyperactivity disorder symptom response was predicted by
      polymorphisms at the serotonin transporter (SLC6A4) intron 2 VNTR (p = .01), with
      a suggested trend for catechol-O-methyltransferase (COMT) (p = .04). Gene * dose
      interactions were noted on math test outcomes for the dopamine D4 receptor (DRD4)
      promoter (p = .008), DRD4 exon 3 VNTR (p = .006), and SLC6A4 promoter
      insertion/deletion polymorphism (5HTTLPR) (p = .02). Irritability was predicted
      by COMT (p = .02). Vegetative symptoms were predicted by 5HTTLPR (p = .003). No
      significant effects were noted for the dopamine transporter (SLC6A3) or
      synaptosomal-associated protein 25 (SNAP25). CONCLUSIONS: This article confirms
      and expands previous studies suggesting that genes moderate ADHD treatment
      response. The ADHD outcomes are not unitary but reflect both behavioral and
      learning domains that are likely influenced by different genes. Future research
      should emphasize candidate gene and genome-wide association studies in larger
      samples, symptom reduction as well as side effects outcomes, and responses over
      full therapeutic dose ranges to assess differences in both gene and gene * dose
      interactive effects.

PMID- 19858761
TI  - Medication and parent training in children with pervasive developmental disorders
      and serious behavior problems: results from a randomized clinical trial.
AB  - OBJECTIVE: Many children with pervasive developmental disorders (PDDs) have
      serious, functionally impairing behavioral problems. We tested whether combined
      treatment (COMB) with risperidone and parent training (PT) in behavior management
      is superior to medication alone (MED) in improving severe behavioral problems in
      children with PDDs. METHOD: This 24-week, three-site, randomized, parallel-groups
      clinical trial enrolled 124 children, aged 4 through 13 years, with PDDs,
      accompanied by frequent tantrums, self-injury, and aggression. The children were
      randomized 3:2 to COMB (n = 75) or MED (n = 49). The participants received
      risperidone monotherapy from 0.5 to 3.5 mg/day (with switch to aripiprazole if
      risperidone was ineffective). Parents in the COMB group (n = 75; 60.5%) received
      a mean of 10.9 PT sessions. The primary measure of compliance was the Home
      Situations Questionnaire (HSQ) score. RESULTS: Primary: intent-to-treat random
      effects regression showed that COMB was superior to MED on HSQ (p = .006) [effect
      size at week 24 (d) = 0.34]. The HSQ score declined from 4.31 (+/- 1.67) to 1.23
      (+/- 1.36) for COMB compared with 4.16 (+/- 1.47) to 1.68 (+/- 1.36) for MED.
      Secondary: groups did not differ on Clinical Global Impressions-Improvement
      scores at endpoint; compared with MED, COMB showed significant reductions on
      Aberrant Behavior Checklist Irritability (d = 0.48; p = .01), Stereotypic
      Behavior (d = 0.23; p = .04), and Hyperactivity/Noncompliance subscales (d =
      0.55; p = .04). Final risperidone mean dose for MED was 2.26 mg/day (0.071
      mg/kg), compared with 1.98 mg/day for COMB (0.066 mg/kg) (p = .04). CONCLUSIONS:
      Medication plus PT resulted in greater reduction of serious maladaptive behavior
      than MED in children with PDDs, with a lower risperidone dose.

PMID- 19858762
TI  - Substance use and the treatment of resistant depression in adolescents.
AB  - OBJECTIVE: Despite the known association between substance use disorders and
      major depressive disorder (MDD) among adolescents, little is known regarding
      substance use among adolescents with MDD. METHOD: Youths with MDD who had not
      improved after an adequate selective serotonin reuptake inhibitor trial (N = 334)
      were enrolled in the Treatment of SSRI-Resistant Depression in Adolescents trial.
      Analyses examined substance use (via the Drug Use Severity Index) and changes
      therein in relation to treatment and depressive symptoms. Adolescents meeting
      substance use disorder criteria via the Schedule for Affective Disorders and
      Schizophrenia for School-Age Children-Present and Lifetime version at baseline
      were excluded. RESULTS: Substance use was common: 28.1% reported repeated
      experimentation at baseline. Substance-related impairment was associated with
      baseline depression severity, older age, physical/sexual abuse, family conflict,
      hopelessness, and comorbid oppositional defiant disorder/conduct disorder. There
      was significant improvement in substance-related impairment among adolescents who
      responded to MDD treatment. Baseline suicidal ideation was higher among the
      subjects who progressed to high substance-related impairment (>= 75th percentile)
      versus those whose substance-related impairment remained low (< 75th percentile),
      and parental depressive symptoms predicted persistence of high substance-related
      impairment during the study. The MDD response was best among the adolescents with
      low 12 week substance-related impairment scores regardless of whether they had
      high or low baseline substance-related impairment. There were no significant
      differential effects of specific treatments, pharmacological or cognitive
      behavioral therapy, on substance use. CONCLUSIONS: Substance use is common among
      adolescents with treatment-resistant MDD. The subjects who had persistently low
      substance-related impairment or who demonstrated reduced substance-related
      impairment had better MDD treatment response, although the direction of this
      association is uncertain.

PMID- 19858763
TI  - Interest in an original methodology to define the optimal dosage of interferon
      alpha-2a in metastatic melanoma patients.
AB  - Interferon-alpha-2a (IFNa) has proven antitumor activity in a variety of
      neoplastic diseases, but no clear modality of administration has been validated.
      The aim of our study was to estimate the optimal dose of continuous subcutaneous
      administration of IFNa in stage IV metastatic melanoma patients. An innovative
      dose-finding approach, combining phase I and phase II trials, was planned to
      evaluate the toxicity and efficacy of four dose levels of IFNa (3, 6, 9, and 12
      MIU/day). Sixteen patients were enrolled in this study. Three patients were
      treated according to the dose-allocation rule with IFNa at 3 MIU/day, nine
      patients at 6 MIU/day, and four patients at 9 MIU/day. Dose-limiting toxicities
      were grade 3 in five patients (three at a dose level of 6 MIU/day and two at a
      dose level of 9 MIU/day). Four clinically relevant responses were obtained, one
      at dose level 3 MIU/day, one at a dose level of 6 MIU/day, and two at a dose
      level of 9 MIU/day. The three final responses, at dose levels of 6 and 9 MIU/day,
      were associated with a dose-limiting toxicity. A dose level of 6 MIU/day was well
      tolerated but did not reach the desired efficacy target of 20%, and a dose level
      of 9 MIU/day was estimated to be too toxic. This original dose-finding
      methodology made it possible to estimate the rate of toxicity and efficacy in a
      small sample of patients without toxicity associated with each dose level.

PMID- 19858764
TI  - Hormone therapy and physical function change among older women in the Women's
      Health Initiative: a randomized controlled trial.
AB  - OBJECTIVE: Although estrogen may be linked to biological pathways that maintain
      higher physical function, the evidence is derived mostly from observational
      epidemiology and therefore has numerous limitations. We examined whether hormone
      therapy affected physical function in women 65 to 79 years of age at enrollment.
      METHODS: This study involves an analysis of the Women's Health Initiative
      randomized controlled trials of hormone therapy in which 922 nondisabled women
      who had previous hysterectomies were randomized to receive estrogen therapy or a
      placebo and 1,458 nondisabled women with intact uteri were randomized to receive
      estrogen + progestin therapy or a placebo. Changes in physical function were
      analyzed for treatment effect, and subgroup differences were evaluated. All women
      completed performance-based measures of physical function (grip strength, chair
      stands, and timed walk) at baseline. These measures were repeated after 1, 3, and
      6 years. RESULTS: Overall, participants' grip strength declined by 12.0%, chair
      stands declined by 3.5%, and walk pace slowed by 11.4% in the 6 years of follow
      up (all P values <0.0001). Hormone therapy, as compared with placebo, was not
      associated with an increased or decreased risk of decline in physical function in
      either the intention-to-treat analyses or in analyses restricted to participants
      who were compliant in taking study pills. CONCLUSIONS: Hormone therapy provided
      no overall protection against functional decline in nondisabled postmenopausal
      women 65 years or older in 6 years of follow-up. This study did not address the
      influence of hormone therapy for women of younger ages.

PMID- 19858765
TI  - Memory for color reactivates color processing region.
AB  - Memory is thought to be constructive in nature, where features processed in
      different cortical regions are synthesized during retrieval. In an effort to
      support this constructive memory framework, the present functional magnetic
      resonance imaging study assessed whether memory for color reactivated color
      processing regions. During encoding, participants were presented with colored and
      gray abstract shapes. During retrieval, old and new shapes were presented in gray
      and participants responded 'old-colored', 'old-gray', or 'new'. Within color
      perception regions, color memory related activity was observed in the left
      fusiform gyrus, adjacent to the collateral sulcus. A retinotopic mapping analysis
      indicated this activity occurred within color processing region V8. The present
      feature specific evidence provides compelling support for a constructive view of
      memory.

PMID- 19858766
TI  - Icariin inhibits neurotoxicity of beta-amyloid by upregulating cocaine-regulated
      and amphetamine-regulated transcripts.
AB  - beta-Amyloid peptide (Abeta) is one of the main protein components of senile
      plaques contributing to Alzheimer's disease and it can induce neuronal apoptosis.
      In this study, it was found that icariin, a flavonoid extracted from Chinese
      Herba-Epimedii, inhibited Abeta42-induced neurotoxicity in a dose-dependent
      manner. The peak dose of icariin was 160 microg/ml. In addition, mRNA and protein
      expressions of cocaine and amphetamine-regulated transcript (CART) were increased
      in Abeta42-treated neurons in the presence of 80 microg/ml icariin. Moreover,
      CART-RNA interference was able to reverse neuroprotection of icariin on Abeta42.
      Furthermore, the expression of CART can be suppressed by extracellular signal
      regulated kinase inhibitor instead of p38/JNK inhibitors, suggesting that icariin
      may be developed into therapeutic agents for Alzheimer's disease and other
      neurodegenerative diseases.

PMID- 19858768
TI  - The clinical value of incidental 18F-fluorodeoxyglucose-avid foci detected on
      positron emission tomography/computed tomography.
AB  - OBJECTIVE: This study was performed to show the malignant potential and clinical
      value of incidental focal 18F-fluorodeoxyglucose (18F-FDG) uptake on positron
      emission tomography/computed tomography (PET/CT) with the confirmation of
      histopathologic findings or with a series of consequent correlative imaging
      methods. METHODS: A total of 2370 18F-FDG-PET/CT studies performed over a 16
      month period in patients with various malignant diseases were retrospectively
      reviewed. Unexpected PET foci that were in an unusual site for metastatic spread
      of known malignancy and not considered to be physiologic uptake were evaluated by
      histopathologic findings or follow-up with correlative imaging methods for a
      period of 1 year or longer. There were 121 such incidental PET lesions in 116
      patients. RESULTS: Seventy-four incidental PET lesions in 70 PET/CT patients were
      investigated further. Forty-seven lesions in 46 patients were lost to follow-up.
      Fifty-nine lesions were confirmed histopathologically. Fifteen lesions were
      evaluated with radiologic methods or instrumental examination. Thirty-six
      incidental PET foci were unexpected malignant or premalignant lesions (1.5% of
      2370 patients and 49% of 74 PET foci). Nineteen of these 36 malignant or
      premalignant lesions were synchronous carcinomas, 14 lesions were unusual or
      unexpected malignant spread of known malignancy and three lesions were
      premalignant colonic adenomas. Thirty-three of 74 incidental PET lesions were of
      benign origin (1.4% of 2370 patients and 44% of 74 PET foci). Five PET foci were
      false-positive findings (7% of 74 lesions). CONCLUSION: The detection of
      incidental 18F-FDG-PET foci on PET/CT may reflect unexpected malignant lesions
      related to unusual malignant spread of primary malignancy or synchronous tumor.
      Follow-up of these PET foci may result in significant change in therapy
      management and early diagnosis of various abnormalities that require a medical
      approach or surgical intervention.

PMID- 19858767
TI  - Chronic stress selectively reduces hippocampal volume in rats: a longitudinal
      magnetic resonance imaging study.
AB  - The notion of uncontrollable stress causing reduced hippocampal size remains
      controversial in the posttraumatic stress disorder literature, because human
      studies cannot discern the causality of effect. Here, we addressed this issue by
      using structural magnetic resonance imaging in rats to measure the hippocampus
      and other brain regions before and after stress. Chronic restraint stress
      produced approximately 3% reduction in hippocampal volume, which was not observed
      in control rats. This decrease was not signficantly correlated with baseline
      hippocampal volume or body weight. Total forebrain volume and the sizes of the
      other brain regions and adrenal glands were all unaffected by stress. This
      longitudinal, within-subjects design study provides direct evidence that the
      hippocampus is differentially vulnerable and sensitive to chronic stress.

PMID- 19858769
TI  - Development and intra-institutional and inter-institutional validation of a
      comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.
AB  - OBJECTIVE: To develop a software tool for quantification of liver and gallbladder
      function, and to assess the repeatability and reproducibility of measurements
      made with it. MATERIALS AND METHODS: The software tool developed with the JAVA
      programming language uses the JAVA2 Standard Edition framework. After manual
      selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study,
      the program calculates differential hepatic bile flow, basal duodeno-gastric bile
      reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with
      deconvolutional analysis and excretion half-time with nonlinear least squares
      fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and
      postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To
      assess intra-observer repeatability and intra-observer reproducibility,
      measurements from 10 normal participants were analyzed twice by three nuclear
      medicine technologists at the primary center. To assess inter-site
      reproducibility, measurements from a superset of 24 normal participants were also
      assessed once by three observers at the primary center and single observer at
      three other sites. RESULTS: For the 24 control participants, mean+/-SD of hepatic
      bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%,
      left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left
      lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction
      was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left
      and right lobe HEF was virtually identical across readers. All measures showed
      high repeatability except for gallbladder bile flow, basal DGBR, and EP, which
      exhibited marginal repeatability. Ejection fraction exhibited high
      reproducibility. There was high concordance among the three primary center
      observers except for basal DGBR, EP, and ER. Concordance between the primary site
      and one of the other sites was high, one was fair, and one was poor. CONCLUSION:
      New United States Food and Drug Administration-approved personal computer-based
      Krishnamurthy Hepato-Biliary Software for quantification of the liver and
      gallbladder function shows promise for consistently repeatable and reproducible
      results both within and between institutions, and may help to promote universal
      standardization of data acquisition and analysis in nuclear hepatology.

PMID- 19858770
TI  - Quantitation of respiratory viruses in relation to clinical course in children
      with acute respiratory tract infections.
AB  - Quantitation of respiratory viruses by PCR could potentially aid in clinical
      interpretation of PCR results. We conducted a study in children admitted with
      acute respiratory tract infections to study correlations between the clinical
      course of illness and semiquantitative detection of 14 respiratory viruses.
      Clinical improvement was associated with reduction of viral quantity after 3 days
      of hospitalization.

PMID- 19858771
TI  - Clinical relevance of placenta examination for the diagnosis of congenital
      toxoplasmosis.
AB  - BACKGROUND: Neonates with congenital toxoplasmosis, even asymptomatic at birth,
      should be treated early to reduce long-term sequelae. Postnatal diagnosis of
      congenital toxoplasmosis is essential because prenatal diagnosis fails to detect
      approximately 15% of cases or cannot be performed when maternal infection is
      acquired in late pregnancy. Detection of parasites in the placenta is one
      diagnostic approach to the early neonatal diagnosis of congenital toxoplasmosis.
      METHODS: The parasitic analyses of 102 placentas from cases of toxoplasmosis
      acquired during gestation were reviewed, with complete biologic follow-up of
      neonates. The value of quantitative PCR and mouse inoculation was assessed, and
      results are discussed in light of prenatal treatment and postnatal outcome.
      RESULTS: Congenital toxoplasmosis was diagnosed in 28 of the 102 cases. A
      prenatal diagnosis was obtained in only 16 cases. Specific IgM was detected in
      57% of the babies at birth. A positive placental examination by PCR and mouse
      inoculation was the only evidence of infection in 3 neonates (11%) who were
      asymptomatic at birth. The sensitivities of PCR and mouse inoculation were 71%
      and 67%, respectively, and the specificities were 97% and 100%. Parasites were
      detected more often when maternal infection was acquired during the third
      trimester of pregnancy (P < 0.01), regardless the type of treatment. The
      sensitivity of IgM detection appeared to be related to maternal treatment since
      IgM was positive in 43% and 75% when mothers were treated or not, respectively (P
      < 0.01). Though 5/7 symptomatic infants had a positive placenta examination,
      there was no correlation between a positive placenta and the presence of clinical
      signs during the first year of life. The positive and negative predictive values
      of placental examination were 91% and 90%, respectively. CONCLUSION: Placental
      examination is an efficient tool for the early diagnosis of congenital
      toxoplasmosis.

PMID- 19858772
TI  - Therapeutic drug monitoring of lopinavir in human immunodeficiency virus-infected
      children receiving adult tablets.
AB  - Because of the lack of a lopinavir/ritonavir (LPV/r) pediatric formulation, 54
      HIV-infected children were given generic LPV/r adult tablets. Of 54 children, 21
      took cut pills to get the appropriate dose. The median (interquartile range) LPV
      trough serum concentration (C trough) was 6.7 (5.0-9.9) mg/L. All the children
      had C trough >1.0 mg/L and 96% had values >4.0 mg/L. LPV/r adult tablets can be
      used in children when it is necessary.

PMID- 19858773
TI  - Antibiotic use in neonatal intensive care units and adherence with Centers for
      Disease Control and Prevention 12 Step Campaign to Prevent Antimicrobial
      Resistance.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) 12-Step Campaign
      to Prevent Antimicrobial Resistance was launched to educate clinicians about
      antimicrobial resistance and provide strategies to improve clinical practice,
      including antimicrobial utilization. METHODS: A multicenter retrospective
      observational study of antibiotic use was performed in 4 tertiary care NICUs to
      assess adherence to the guidelines defined by the CDC 12-Step Campaign using
      predetermined criteria. Fifty infants per NICU were identified who received
      intravenous antibiotics at greater than 72 hours of age. Antibiotic regimens,
      clinical and microbiologic data, and indications for initiation and continuation
      of antibiotics (after 72 hours of use) were recorded. Inappropriate utilization
      was characterized at initiation, continuation, by agent, and by CDC 12-Step.
      RESULTS: Two hundred neonates received 323 antibiotic courses totaling 3344
      antibiotic-days. Ninety (28%) courses and 806 (24%) days were judged to be
      nonadherent to a CDC 12-Step. Inappropriate use was more common with continuation
      of antibiotics (39%) than with initiation (4%) of therapy. Vancomycin was the
      most commonly used drug (n = 895 antibiotic-days) of which 284 (32%) days were
      considered inappropriate. Carbapenems were used less frequently (n = 310
      antibiotic-days), and 132 (43%) of these days were inappropriate. Common reasons
      for nonadherence at the time of continuation included failure to narrow
      antibiotic coverage after microbiologic results were known and prolonged
      antibiotic prophylaxis after surgery with chest tube placement. CONCLUSIONS: The
      CDC 12-Step Campaign can be modified for neonatal populations. Inappropriate
      antibiotic prescribing was common in the study NICUs. Improvement efforts should
      target antibiotic use 72 hours after initiation, particularly focusing on
      narrowing therapy and instituting protocols to limit prophylaxis.

PMID- 19858774
TI  - Modern trends in mortality from meningococcal disease in Australia.
AB  - Between 1979 and 2006, there were 610 deaths recorded as due to meningococcal
      disease in Australia. Mortality rates per capita consistently increased on
      average by 6% per annum between 1979 and 2002, but then fell significantly in
      2003, coinciding with the introduction of the meningococcal C conjugate vaccine.
      In 2002, the mortality rate was 0.24 per 100,000. In the 4 years since, it fell
      progressively to 0.06 per 100,000. Since the introduction of conjugate Hib and
      pneumococcal vaccines, meningococcal disease has emerged as the number 1
      infectious cause of death in children but conjugate meningococcal C vaccine
      appears to have greatly reduced total meningococcal disease deaths.

PMID- 19858775
TI  - Effects of rho-kinase inhibition on pulmonary hypertension, lung growth, and
      structure in neonatal rats chronically exposed to hypoxia.
AB  - Rho-kinase (ROCK) inhibitors prevent pulmonary hypertension (PHT) in adult
      rodents, but little is known about their effects on the neonatal lung. Our
      objective was to examine the effects of ROCK inhibition on chronic hypoxia (CH)
      induced PHT and abnormal lung structure in the neonatal rat. Pups were exposed to
      air or CH from postnatal d 1-14 while receiving Y-27632 (5 or 10 mg x kg(-1) x d(
      1)), fasudil (20 mg x kg(-1) x d(-1)), or saline intraperitoneally. Relative to
      air, CH-exposed pups had increased pulmonary vascular resistance, right
      ventricular hypertrophy, arterial medial wall thickening, and abnormal distal
      airway morphology characterized by septal thinning and decreased secondary
      septation. Treatment with 10 mg/kg Y-27632 or fasudil attenuated the structural
      and hemodynamic changes of PHT while having no effect on septal thinning or
      inhibited secondary septation. In addition, Y-27632 (10 mg/kg) and fasudil
      augmented CH-induced somatic growth restriction. Pulmonary arteries of CH-exposed
      pups had increased ROCK activity, up-regulated expression of PDGF-BB and
      increased smooth muscle DNA synthesis, all of which were attenuated by treatment
      with 10 mg/kg Y-27632. Systemically administered ROCK inhibitors prevented PHT in
      the CH-exposed neonatal rat but at the cost of inhibited somatic growth. Limiting
      effects on vascular remodeling likely resulted, in major part, from attenuated
      vascular PDGF-BB/beta-receptor signaling.

PMID- 19858776
TI  - Placental features of chorioamnionitis colonized with Ureaplasma species in
      preterm delivery.
AB  - Ureaplasma spp. is detected in the urogenital tract, including the vagina,
      cervix, chorioamnion, and placenta. Their colonization is associated with
      histologic chorioamnionitis (CAM), often observed in placentas from preterm
      delivery. We isolated Ureaplasma spp. from 63 preterm placentas among 151
      specimens, which were delivered at <32 wk of gestation. Of the 63 placentas, 52
      (83%) revealed CAM in cultures positive for Ureaplasma spp., however, CAM was
      observed only in 30% (26/88) of cultures negative for Ureaplasma spp. (p < 0.01).
      Colonization by Ureaplasma spp. was an independent risk factor for CAM (OR,
      11.27; 95% CI, 5.09-24.98). Characteristic neutrophil infiltration was observed
      in the amnion and subchorion (bistratified pattern) in cultures positive for
      Ureaplasma spp. FISH analysis of CAM placenta with male infant pregnancy
      indicated that bistratified infiltrated neutrophils showed the XX karyotype and
      umbilical vein infiltrated neutrophils showed XY karyotype. The distribution of
      sulfoglycolipid, the receptor of Ureaplasma spp., was mainly detected in the
      amnion. Ureaplasmal urease D protein and ureB gene were both detected in the
      amnion, indicating direct colonization by Ureaplasma spp.

PMID- 19858778
TI  - Molecular assessment of thymus capabilities in the evaluation of T-cell
      immunodeficiency.
AB  - T-cell immunodeficiency may pose a diagnostic challenge to clinicians, especially
      when the basic T-cell immune workup is not sufficiently informative. An intensive
      assessment of thymus capabilities that involves either measuring the recent
      thymic emigrant cells or analyzing the T-cell receptor (TCR) repertoire is often
      required to estimate the severity and nature of the immune disorder. A
      comprehensive T-cell immune workup, including TCR excision circles (TRECs) and
      TCR repertoire analyses, was performed in three patients with various degrees of
      severity of T-cell immunodeficiency. All three patients had normal peripheral
      CD3+ T lymphocytes. TCR repertoire analysis revealed oligoclonal (patient 1),
      restricted (patient 2), and near-normal (patient 3) patterns. TREC quantification
      was significantly reduced in patients 1 and 2 but normal in patient 3. Based on
      clinical features at presentation and at follow-up, and supported by the results
      of immunologic studies, patients 1 and 2 were diagnosed as having significant T
      cell immunodeficiency and patient 3 as having T-cell immunocompetence. Assessment
      of thymus capabilities by TRECs and TCR repertoire analyses is helpful in
      diagnosing patients with T-cell immunodeficiency and should be part of the
      evaluation of every patient suspected of having that condition.

PMID- 19858777
TI  - Skin thickness in children treated with daily or periodical inhaled budesonide
      for mild persistent asthma. The Helsinki early intervention childhood asthma
      study.
AB  - In adults, asthma treatment with high doses of inhaled corticosteroids has
      resulted in dermal thinning. The aim of this study was to investigate the skin
      thickness in children with asthma during budesonide treatment. In a double-blind
      study, 113 children, 5-10 y old, with persistent asthma received budesonide 400
      microg twice daily for 1 mo and thereafter 200 microg twice daily for 5 mo.
      Thereafter, 56 children received 100 microg twice daily for 1 y, whereas 57 other
      children used budesonide periodically for exacerbations. An additional 54
      children were treated with disodium cromoglycate (DSCG) for 18 mo. Skin thickness
      was measured on each forearm before and after treatment for 6, 12, and 18 mo
      using a 20-MHz high-resolution ultrasonic device. The initial 6-mo budesonide
      treatment resulted in a greater reduction in mean skin thickness in the forearms
      compared with DSCG (right: -35.9 versus -5.9 microm; p = 0.004; left: -30.6
      versus -7.3 microm; p = 0.03). At month 18, the inter-group differences were no
      longer significant. Budesonide inhalations in daily doses of 400-800 microg in
      prepubertal children with newly detected asthma may cause minor dermal thinning.
      The changes were reversible during low dose or periodic treatment with
      budesonide.

PMID- 19858779
TI  - Improving accuracy of Tay Sachs carrier screening of the non-Jewish population:
      analysis of 34 carriers and six late-onset patients with HEXA enzyme and DNA
      sequence analysis.
AB  - The purpose of this study was to determine whether combining different testing
      modalities namely beta-hexosaminidase A (HEXA) enzyme analysis, HEXA DNA common
      mutation assay, and HEXA gene sequencing could improve the sensitivity for
      carrier detection in non-Ashkenazi (AJ) individuals. We performed a HEXA gene
      sequencing assay, a HEXA DNA common mutation assay, and a HEXA enzyme assay on 34
      self-reported Tay-Sachs disease (TSD) carriers, six late-onset patients with TSD,
      and one pseudodeficiency allele carrier. Sensitivity of TSD carrier detection was
      91% for gene sequencing compared with 91% for the enzyme assay and 52% for the
      DNA mutation assay. Gene sequencing combined with enzyme testing had the highest
      sensitivity (100%) for carrier detection. Gene sequencing detected four novel
      mutations, three of which are predicted to be disease causing [118.delT, 965A-->T
      (D322V), and 775A-->G (T259A)]. Gene sequencing is useful in identifying rare
      mutations in patients with TSD and their families, in evaluating spouses of known
      carriers for TSD who have indeterminate enzyme analysis and negative for common
      mutation analysis, and in resolving ambiguous enzyme testing results.

PMID- 19858780
TI  - Gene-gene interactions in folate and adenosine biosynthesis pathways affect
      methotrexate efficacy and tolerability in rheumatoid arthritis.
AB  - OBJECTIVE: As no single nucleotide polymorphism has emerged as pivotal to predict
      the lack of efficacy and dose-limiting toxicities to methotrexate (MTX), we
      evaluated the contribution of gene-gene interactions to the effects of this
      prodrug in rheumatoid arthritis. METHODS: A total of 255 patients treated with
      MTX for at least 3 months were evaluated with efficacy assessed using the
      European League Against Rheumatism response criteria or a physician's assessment
      of patient's response to MTX visual analog scale. Gastrointestinal and
      neurological idiosyncrasies were recorded in 158 patients. Fourteen single
      nucleotide polymorphisms in folate and adenosine biosynthesis pathways were
      measured and detection of gene-gene interactions was performed using multifactor
      dimensionality reduction, a method that reduces high-dimensional genetic data
      into a single dimension of predisposing or risk-genotype combinations. RESULTS:
      Efficacy to MTX (53% responders) was associated with high-order epistasis among
      variants in inosine-triphosphate pyrophosphatase, aminoimidazole-carboxamide
      ribonucleotide transformylase, and reduced folate carrier genes. In the absence
      of predisposing genotype combinations, a 3.8-fold lower likelihood of efficacy
      was observed (vs. in their presence, 95% confidence interval: 2.2-6.4; P<0.001).
      Increasing MTX polyglutamate concentrations tended to partially overcome this
      selective disadvantage. Idiosyncrasies occurred in 29% of patients. In the
      presence of risk-genotype combinations among variants in methylene
      tetrahydrofolate reductase, gamma-glutamyl-hydrolase, thymidylate synthase,
      serine hydroxymethyltransferase, and inosine-triphosphate pyrophosphatase genes,
      an 8.9-fold higher likelihood to exhibit toxicities was observed (vs. in their
      absence, 95% confidence interval: 3.6-21.9; P<0.001). False-positive report
      probabilities were below 0.2, thereby indicating that true signals were likely
      detected in this cohort. CONCLUSION: These data indicate that gene-gene
      interactions impact MTX efficacy and tolerability in rheumatoid arthritis.

PMID- 19858781
TI  - Human UDP-glucuronosyltransferase UGT2A2: cDNA construction, expression, and
      functional characterization in comparison with UGT2A1 and UGT2A3.
AB  - OBJECTIVES: Characterize the expression and glucuronidation activities of the
      human uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT) 2A2. METHOD:
      UGT2A1 was cloned from nasal mucosa mRNA. Synthetic cDNA for UGT2A2 was
      constructed assuming exon sharing between UGT2A1 and UGT2A2 (Mackenzie et al.,
      Pharmacogenetics and Genomics 2005, 15:677-685). Exon 1 of UGT2A2 was amplified
      from genomic DNA and combined with exons 2-6 of UGT2A1. UGT2A3 was cloned from
      liver mRNA. Quantitative reverse-transcribed-PCR (RT-PCR) was used to evaluate
      the expression of all the three UGTs of subfamily 2A in different tissues.
      Recombinant UGT2A1, UGT2A2 and UGT2A3 were expressed in baculovirus-infected
      insect cells and analyzed for glucuronidation activity towards different
      substrates. RESULTS: DNA sequencing of RT-PCR products from human nasal mucosa
      mRNA, confirmed exon sharing between UGT2A1 and UGT2A2. In addition, it indicated
      that the N-terminal signal peptide sequence of UGT2A2 is the longest among the
      human UGTs. Quantitative RT-PCR revealed that both UGT2A1 and UGT2A2 are mainly
      expressed in the nasal mucosa, and that their expression level in fetal samples
      was much higher than in adults. Activity assays with recombinant UGTs 2A1-2A3
      showed broad substrate selectivity for UGT2A1 and UGT2A2. Although
      glucuronidation rates and substrate affinities were mostly higher in UGT2A1, the
      Km values for UDP-glucuronic acid were similar in both UGTs. In addition, there
      were regioselectivity differences between the two UGTs and, with a few
      substrates, particularly ethinylestradiol, the activity of UGT2A2 was higher.
      CONCLUSION: UGT2A2 is mainly expressed in the nasal mucosa and it has
      glucuronidation activity towards several different endobiotic and xenobiotic
      substrates.

PMID- 19858782
TI  - Bipolar hypertrophic herpes: an unusual presentation of acyclovir-resistant
      herpes simplex type 2 in a HIV-infected patient.
AB  - Hypertrophic pseudo tumoral herpetic lesion is an uncommon presentation in
      immunocompromized hosts that can be refractory to established therapies. We
      describe bipolar anal and tonsilar herpetic tumoral lesions related to acyclovir
      resistant HSV-2 in a human immunodeficiency virus-infected patient. Treatment
      with valacyclovir, cidofovir, and thalidomide failed and surgical excision was
      required.

PMID- 19858783
TI  - Polyradiculoneuropathy associated to human herpesvirus 2 in an HIV-1-infected
      patient (Elsberg syndrome): case report and literature review.
AB  - Peripheral nerve disorders are a common complication in HIV patients, reaching
      15% of them. Several patterns and aetiologies have been described, being
      lumbosacral poliradiculoneuropathy one of them. We describe an HIV-1-infected
      patient who developed lumbosacral poliradiculoneuropathy caused by Human
      herpesvirus 2 and review the literature about this uncommon condition.

PMID- 19858784
TI  - Peace is not simply the absence of war.

PMID- 19858785
TI  - Residents' voices must be heard.

PMID- 19858786
TI  - Why start an academy?

PMID- 19858790
TI  - The impact of pass/fail grading.

PMID- 19858791
TI  - Commentary: Health care reform and its potential impact on academic medical
      centers.
AB  - President Obama's administration has committed to significant changes in the
      current health care system to address three issues: access, cost, and quality.
      Leaders at academic medical centers (AMCs) must acknowledge the root cause of the
      problems within the current system, recognize potential change initiatives,
      contemplate the changing role that AMCs will play in the health care system of
      the future, and begin to adapt and respond. The underlying root cause of the
      problem with our health care system is excessive costs. Although many factors
      contribute to excess costs, the most important factor is overuse of expensive
      modalities. The administration will try to impact change by stressing preventive
      care, improving medical practice with the purpose of achieving greater value, and
      changing the reimbursement system from fee for service to other reimbursement
      approaches that provide greater incentives for more coordinated and integrated
      systems of care. It is argued in this commentary that ultimately reform will lead
      to some form of a managed care model with limits on spending. Highly integrated
      health care systems will be in the best position to produce more efficient care
      that provides value. The authors posit that AMCs have the unique opportunity of
      shaping integration in many regions of the country and highlight efforts at the
      University of Kentucky to develop a health care system to serve the commonwealth.
      Change is inevitable. Being proactive rather than reactive may be important to
      secure the future of AMCs.

PMID- 19858792
TI  - Artist's statement: heart.

PMID- 19858793
TI  - Commentary: Flexner Redux 2010: graduate medical education in the United States.
AB  - The author posits that if Abraham Flexner could be brought back to write a report
      to address the same question that his 1910 report answered-How are doctors being
      prepared for practice?-he would not focus on the state of medical students'
      education, because today's medical students no longer enter practice on
      graduation from medical school. Instead, he would ask how the country's graduate
      medical education (GME) system is preparing residents for clinical practice. Such
      a report is needed because (as concluded by a variety of sources, including
      recent reports by the Institute of Medicine) GME training must be changed as part
      of the effort to improve medical care quality. Despite this finding, professional
      organizations that regulate how GME is designed and conducted have been unwilling
      to make substantive changes in the ways residents are being prepared for
      practice. The author reviews the reasons for this, emphasizes the need for a new
      Flexner-type report to make the public aware of the training deficiencies so the
      public could exert pressure on government officials to take action, describes
      groups that have already recognized the problem and proposed solutions (such as
      having individual programs held accountable for their residents' performance in
      practice), and makes recommendations, such as (1) having the Medicare program,
      the single largest payer of GME costs, require certain needed reforms in
      residents' training, and (2) modernizing state laws so that residents completing
      training would have to demonstrate that they are adequately prepared to enter
      practice before being granted licenses.

PMID- 19858794
TI  - Commentary: The relationship status of digital media and professionalism: it's
      complicated.
AB  - The rising popularity of digital applications, such as social networking, media
      share sites, and blogging, has significantly affected how medical trainees
      interact with educators, colleagues, and the public. Despite the increased
      popularity and use of such applications amongst the current generation of
      trainees, medical educators have little evidence or guidance about preventing
      misuse and ensuring standards for professional conduct. As trainees become more
      technologically savvy, it is the responsibility of medical educators to
      familiarize themselves not only with the advantages of this technology but also
      with the potential negative effects of its misuse. Professionalism,
      appropriateness for public consumption, and individual or institutional
      representation in digital media content are just some of the salient issues that
      arise when considering the ramifications of trainees' digital behavior in the
      absence of established policies or education on risk. In this commentary the
      authors explore the rising use of digital media and its reflection of medical
      trainees' professionalism. To address possible issues related to professionalism
      in digital media, the authors hypothesize potential solutions, including
      exploring faculty familiarity with digital media and policy development,
      educating students on the potential risks of misuse, and modeling professionalism
      in this new digital age.

PMID- 19858795
TI  - Commentary: Evaluating faculty productivity in research: an interesting approach,
      but questions remain.
AB  - Academic institutions must have strategies for evaluating research productivity
      by faculty. Such strategies are useful in guiding resource allocations for the
      research enterprise, for decisions on faculty promotions, and for broader
      institutional planning, including program development. Commonly, decisions about
      research space utilization, and funding to support the space, are considered
      within the purview of the institutional administration. Peer review, in
      manuscript and grant submissions and the promotions process, is more commonly
      used to evaluate the impact of faculty research. The article by Iyengar et al in
      this issue of Academic Medicine takes an interesting approach to evaluate
      research productivity of individual faculty by integrating benchmarks for
      research funding and publication impact. The strategy of using these benchmarks
      to partition faculty into quadrants to guide faculty development activities is
      clever and useful. Less clear are the philosophy and long-term utility of the
      approach. The applicability to the stated goal of promoting multidisciplinary and
      interdisciplinary translational research is not obvious, nor is it apparent that
      faculty will continue to view decisions as transparent and fair over the longer
      term. Nevertheless, the authors' article is a welcome contribution at a time when
      many institutions are struggling with issues of evaluating faculty investigators
      and allocating resources for research.

PMID- 19858796
TI  - Gathering in groups: peace advocacy in health professional associations.

PMID- 19858797
TI  - Building a health-peace movement: academic medicine's role in generating
      solutions to global problems.

PMID- 19858798
TI  - How academic medicine can contribute to peace-building efforts worldwide.

PMID- 19858799
TI  - Academic medicine as a bridge to peace: building Arab and Israeli cooperation.

PMID- 19858800
TI  - Teaching and learning moments. A lesson in ethics.

PMID- 19858801
TI  - Academic medicine should start at home.

PMID- 19858802
TI  - Institutions' expectations for researchers' self-funding, federal grant holding,
      and private industry involvement: manifold drivers of self-interest and
      researcher behavior.
AB  - BACKGROUND: Private industry involvement is viewed as tainting research with self
      interest, whereas public funding is generally well regarded. Yet, dependence on
      "soft money" also triggers researcher and university self-interest. No empirical
      research has compared these factors' effects on academic researchers' behaviors.
      METHOD: In 2006-2007, a survey was mailed to 5,000 randomly selected biomedical
      and social science faculty at 50 top-tier research universities in the United
      States. Measures included a university's expectations or nonexpectations that
      researchers obtain external grant funding, the receipt or nonreceipt of public
      research funding, any relationships with private industry, and research-related
      behaviors ranging from the ideal, to the questionable, to misconduct. RESULTS:
      Being expected to obtain external funding and receiving federal research funding
      were both associated with significantly higher reports of 1 or more of 10 serious
      misbehaviors (P<.05) and neglectful or careless behaviors (P<.001). Researchers
      with federal funding were more likely than were those without to report having
      carelessly or inappropriately reviewed papers or proposals (9.6% versus 3.9%;
      P<.001). Those with private industry involvement were more likely than were those
      without to report 1 or more of 10 serious misbehaviors (28.5% versus 21.5%;
      P=.005) and to have engaged in misconduct (12.2% versus 7.1%; P=.004); they also
      were less likely to have always reported financial conflicts (96.0% versus 98.6%,
      P<.001). CONCLUSIONS: The free play of university and individual self-interests,
      combined with and contributing to the intense competition for research funding,
      may be undermining scientific integrity.

PMID- 19858803
TI  - Perspective: A perfect storm: the convergence of bullet points, competencies, and
      screen reading in medical education.
AB  - Three distinct phenomena are currently at play in medical education: (1) the
      pervasive use of PowerPoint in teaching, (2) the wholesale application of
      competency models, and (3) the shift from paper reading to screen reading
      regardless of course, text, or genre. Finding themselves placed at this
      intersection, students encounter fewer and fewer opportunities to practice some
      of the very cognitive and affective habits medical educators say they value in
      physicians, particularly critical reflection and deliberation, an eye for nuance,
      context, and ambiguity, and an appreciation that becoming a doctor involves more
      than learning content or performing skills. This article confronts these
      phenomena singly and then at their intersection, which may discourage, even
      dismantle, many of these habits. The author proposes that the rapid shift over
      the past decade to a technology-driven, competency-oriented environment in
      medical education is the medical educators' creation, one that sets up conditions
      for a perfect cognitive storm.

PMID- 19858805
TI  - Measuring motivational characteristics of courses: applying Keller's
      instructional materials motivation survey to a web-based course.
AB  - PURPOSE: The Instructional Materials Motivation Survey (IMMS) purports to assess
      the motivational characteristics of instructional materials or courses using the
      Attention, Relevance, Confidence, and Satisfaction (ARCS) model of motivation.
      The IMMS has received little use or study in medical education. The authors
      sought to evaluate the validity of IMMS scores and compare scores between
      standard and adaptive Web-based learning modules. METHOD: During the 2005-2006
      academic year, 124 internal medicine residents at the Mayo School of Graduate
      Medical Education (Rochester, Minnesota) were asked to complete the IMMS for two
      Web-based learning modules. Participants were randomly assigned to use one module
      that adapted to their prior knowledge of the topic, and one module using a
      nonadaptive design. IMMS internal structure was evaluated using Cronbach alpha
      and interdimension score correlations. Relations to other variables were explored
      through correlation with global module satisfaction and regression with knowledge
      scores. RESULTS: Of the 124 eligible participants, 79 (64%) completed the IMMS at
      least once. Cronbach alpha was >or=0.75 for scores from all IMMS dimensions.
      Interdimension score correlations ranged 0.40 to 0.80, whereas correlations
      between IMMS scores and global satisfaction ratings ranged 0.40 to 0.63 (P<.001).
      Knowledge scores were associated with Attention and Relevance subscores (P=.033
      and .01, respectively) but not with other IMMS dimensions (P>or=.07). IMMS scores
      were similar between module designs (on a five-point scale, differences ranged
      from 0.0 to 0.15, P>or=.33). CONCLUSIONS: These limited data generally support
      the validity of IMMS scores. Adaptive and standard Web-based instructional
      designs were similarly motivating. Cautious use and further study of the IMMS are
      warranted.

PMID- 19858806
TI  - Is there a relationship between high-quality performance in major teaching
      hospitals and residents' knowledge of quality and patient safety?
AB  - PURPOSE: The relationship of the quality of teaching hospitals' clinical
      performance to resident education in quality and patient safety is unclear. The
      authors studied residents' knowledge of these areas in major teaching hospitals
      with higher- and lower-quality performance rankings. They assessed the presence
      of formal and informal quality curricula to determine whether programmatic
      differences exist. METHOD: The authors used qualitative research methodology with
      purposeful sampling. They gathered data from individual structured interviews
      with residents and key educational and quality leaders in six medical schools and
      teaching hospitals, which represented a range of quality performance rankings,
      geographic regions, and public or private status. RESULTS: No relationship
      emerged between a hospital's quality status, residents' curriculum, and the
      residents' understanding of quality. Residents' definitions of quality and safety
      and their knowledge of the practice-based learning and systems-based practice
      competencies were indistinguishable between hospitals. Residents in all programs
      had extensive patient safety knowledge acquired through an informal curriculum in
      the hospital setting. A formal curriculum existed in only two programs, both of
      them ambulatory settings. CONCLUSIONS: Residents' learning about quality and
      patient safety is extensive, largely through a positive informal curriculum in
      the teaching hospital and, less frequently, via a formal curriculum. No
      relationship was found between the quality performance of the teaching hospital
      and the residents' curriculum or understanding of quality or safety. Residents
      seem to learn through an informal curriculum provided by hospital initiatives and
      resources, and thus these data suggest the importance of major teaching hospitals
      in quality education.

PMID- 19858807
TI  - "I can do patient care on my own": autonomy and the manager role.
AB  - PURPOSE: An internal medicine (IM) residency program redesigned its second year,
      the Manager Year, to restore balance among autonomy, supervision, and clinical
      competence. This study examined the response of residents and some supervising
      attendings to this innovation. METHOD: In this qualitative study-part of a total
      program evaluation-two authors gathered data from 36 second-year resident
      managers, 3 third-year residents, and 8 attendings through semistructured
      interviews between spring 2005 and spring 2007. All resident-managers in 2005
      2006 and all but one in 2006-2007 were interviewed. From verbatim transcripts,
      two of the authors coded the responses into themes; then all four reviewed and
      revised these themes. RESULTS: Coding revealed that second-year residents
      associated four qualities with their experience as managers: ownership of
      patients, accountability to others, competence in patient management skills, and
      personal satisfaction. They described the manager role as being as being "on your
      own." They were accountable to fellow managers, attendings, and nursing staff at
      a different level from that of an intern. Without an intern to teach, they
      learned critical management skills to complete their work. They became adult
      learners around their own patient cases. CONCLUSIONS: Successful preparation of
      physicians for independent practice requires a careful balance between autonomy
      and supervision, increasing the former during the training program sequence. For
      resident-managers, the assignment as principle caregiver occurs at the interface
      between the two. Managers identify themselves as a great deal more autonomous
      while still valuing attending supervision and input from co-managers to meet
      responsibilities.

PMID- 19858808
TI  - The unintended consequences of portfolios in graduate medical education.
AB  - Portfolios have emerged in graduate medical education despite lack of consensus
      on their definition, purpose, or usefulness. Portfolios can be used as a tool for
      residents to record their accomplishments, reflect on their experiences, and gain
      formative feedback. This exercise may help prepare physicians for lifelong
      learning as well as enhance patient care. The Accreditation Council for Graduate
      Medical Education has endorsed and may soon require the use of portfolios as an
      assessment tool to evaluate resident competence. However, using portfolios for
      summative evaluation purposes such as making high-stakes decisions on resident
      promotion or matriculation may deter resident candidness. In addition, the use of
      portfolios in clinical settings raises issues unique to the health care setting
      such as patient privacy, disclosure of clinical information, and professional
      liability exposure of physicians. It is not clear that peer-review statutes that
      sometimes protect educational materials used in teaching and evaluation of
      residents would also bar disclosure and/or evidentiary use of portfolio contents.
      Is the teaching institution, resident, or graduate vulnerable to requests and
      subpoenas for the portfolio contents? If so, then a resident's documentation of
      insecurities, suboptimal performance, or bad outcomes would be ripe for discovery
      in a medical malpractice lawsuit. If embraced too quickly and without sufficient
      reflection on the nuances of implementation, this well-intentioned initiative may
      present unintended legal consequences.

PMID- 19858809
TI  - Teaching and learning moments. Food insecurity on three dollars a day.

PMID- 19858810
TI  - A set of principles, developed by residents, to guide Canadian residency
      education.
AB  - With so much invested in the clinical competency of physicians, adequate and
      appropriate mechanisms are needed to ensure that educational systems provide the
      highest-quality training possible and are responsive both to the changing demands
      of the patient population and to changing technologies and research. After a
      literature review, the authors concluded that there are no established criteria
      or principles, from a learners' perspective, that set out goals for the delivery
      and evaluation in Canada of quality postgraduate medical education. The authors
      initiated the process of developing a set of principles of medical education
      based on residents' perspectives by compiling a list of issues and concepts that
      were felt to be important to creating the "ideal" postgraduate medical education
      system. This list of issues was divided into broad categories before presentation
      by the authors for Canada-wide discussion, reflection, and further refinement of
      concepts and issues across a nine-month period. The process eventually resulted
      in the final consensus-driven and iterative development of the main categories
      and the final principles that were adopted by the Canadian Association of
      Internes and Residents (CAIR). The authors present this set of principles and
      propose that they be used as a template to guide postgraduate medical education
      and against which changes to the system can be evaluated. CAIR will use these
      principles in a number of ways, including evaluation, education, and quality
      assurance.

PMID- 19858811
TI  - Medicine residents' self-perceived competence in end-of-life care.
AB  - PURPOSE: Internal medicine residents frequently provide end-of-life care, yet
      feel inadequately trained and uncomfortable providing this care, despite efforts
      to improve end-of-life care curricula. Understanding how residents' experiences
      and attitudes affect their perceived competence in providing end-of-life care is
      important for targeting educational interventions. METHOD: Medicine residents
      (74) at the University of Washington and Medical University of South Carolina
      enrolled in a trial investigating the efficacy of a communication skills
      intervention to improve end-of-life care. On entry to the study in the fall of
      2007, residents completed a questionnaire assessing their prior experiences,
      attitudes, and perceived competence with end-of-life care. Multivariate
      regression analysis was performed to assess whether attitudes and experiences
      with end-of-life care were associated with perceived competence, controlling for
      gender, race/ethnicity, training year, training site, and personal experience
      with death of a loved one. RESULTS: Residents had substantial experience
      providing end-of-life care. In an adjusted multivariate model including attitudes
      and clinical experience in end-of-life care as predictors, only clinical
      experience providing end-of-life care was associated with self-perceived
      competence (P=.015). CONCLUSIONS: Residents with more clinical experience during
      training had greater self-perceived competence providing end-of-life care.
      Increasing the quantity and quality of the end-of-life care experiences during
      residency with appropriate supervision and role modeling may lead to enhanced
      skill development and improve the quality of end-of-life care. The results
      suggest that cultivating bedside learning opportunities during residency is an
      appropriate focus for educational interventions in end-of-life care education.

PMID- 19858814
TI  - Defining and describing medical learning communities: results of a national
      survey.
AB  - PURPOSE: To investigate what is meant by learning community in medical education
      and to identify the most important features of current medical education learning
      communities. METHOD: After a literature review, the authors surveyed academic
      deans of all U.S. and Canadian medical schools and colleges (N=124) to identify
      those that had implemented a learning community. Those with student learning
      communities (N=18) answered a series of questions about the goals, structure,
      function, benefits, and challenges of their communities. RESULTS: The most common
      primary goals included fostering communication among students and faculty;
      promoting caring, trust, and teamwork; helping students establish academic
      support networks; and helping students establish social support networks. Most
      deans said that students remained in the same community for all four years of
      medical school and that communities were linked to specific faculty and/or peer
      advisors. For most schools, communities included students from many class years,
      and participation was mandatory. Curricular purposes included professionalism
      training, leadership development, and service learning. Almost all schools had
      social functions related to their communities, and most provided career planning,
      group mentoring, and personal counseling. CONCLUSIONS: Learning communities in
      medical education demonstrate diverse approaches to achieving the general goal of
      enhanced student learning. Medical school leaders considering learning
      communities should determine the goals they want to accomplish and be open to
      adopting different approaches based on local needs. Evaluation and effective
      monitoring of evolution are needed to determine the best approaches for different
      needs and to assess impact on students and faculty.

PMID- 19858812
TI  - Improving chronic care of type 2 diabetes using teams of interprofessional
      learners.
AB  - PURPOSE: To improve the care and outcomes of adult patients with type 2 diabetes
      by teaching interprofessional teams of learners the principles and practices of
      the Improving Chronic Illness Care Model. METHOD: The study population consisted
      of 384 adult patients with type 2 diabetes. The study design was a nonrandomized,
      parallel-group, clinical trial conducted during 18 months in the University of
      California, San Francisco internal medicine clinics. Interprofessional team care
      provided by primary care internal medicine residents, nurse practitioner
      students, and pharmacy students was compared with usual care by internal medicine
      residents only. Processes of care, clinical status, and health utilization were
      measured in both patient groups. Learner outcomes also were assessed and
      compared. RESULTS: At study completion, intervention patients more frequently
      received assessments of glycosolated hemoglobin (79% versus 67%; P=.01), LDL-C
      (69% versus 55%; P=.009), blood pressure (86% versus 79%; P=.08),
      microalbuminuria (40% versus 30%; P=.05), smoking status assessment (43% versus
      31%; P=.02), and foot exams (38% versus 20%; P=.0005). Intervention patients had
      more planned general medicine visits (7.9+/-6.2 versus 6.2+/-5.7; P=.006) than
      did control patients. Interprofessional learners rated themselves significantly
      higher on measures of accomplishment, preparation, and success for chronic care
      than did the usual care learners. CONCLUSIONS: Interprofessional team care by
      learners was effective in improving quality of care for adult patients with
      diabetes treated in general medicine clinics. The chronic illness framework
      resulted in more appropriate health care utilization.

PMID- 19858815
TI  - Medicine and the arts. Hospital. Commentary.

PMID- 19858817
TI  - Doors.

PMID- 19858818
TI  - Using a Socratic dialogue to tackle thorny issues of psychiatry.
AB  - Medical students often experience significant cognitive dissonance as they
      attempt to understand psychiatry. After the security of lab values and medical
      tests that characterize much of medical practice, the ambiguity of seemingly
      subjectively obtained information characteristic of psychiatry often leaves
      students somewhat uncomfortable with how psychiatric diagnoses are made and
      understood. This is, at its root, an issue of epistemology: How do we know what
      we say we know? Psychiatry can seem "fuzzy" to medical students, and it behooves
      psychiatry educators to explicitly address this discomfort but, at the same time,
      not apologize for the differences between psychiatry and "the rest of medicine."
      In this article, the author strives to emphasize that this kind of
      epistemological challenge is ancient and esteemed, represented to some extent in
      the writings of Plato (who believed that we measure the world by comparing our
      experience with our innate sense of what we know is true) and Aristotle (who
      insisted that what we know is based largely on what we can measurably
      experience). Using humor, an imagined conversation among these ancient
      philosophers and a modern psychiatrist-medical educator might help to dispel some
      of the discomfort that psychiatry education sometimes engenders among future
      physicians. The author presents an example of such a conversation. After a brief
      discussion of the epistemological differences characteristic of Platonic and
      Aristotelian views, students could be shown a script similar to the example
      script and then asked to discuss and debate the arguments elucidated. Perhaps
      even better, students could be asked to write their own debates based on how
      Plato or Aristotle would be expected to behave.

PMID- 19858820
TI  - International medical graduate-patient communication: a qualitative analysis of
      perceived barriers.
AB  - PURPOSE: International medical graduates (IMGs) represent a substantial portion
      of all medical residents in the United States. Yet, IMGs may be disadvantaged in
      their communications with U.S. patients for a variety of reasons. The authors
      conducted a qualitative study to examine IMGs' perceptions of the barriers to
      their communication with patients. METHOD: A convenience sample of 12 IMGs
      participated in interviews that lasted 1 to 1.5 hours. Residents from the
      Caribbean, Colombia, Denmark, India, Iran, Pakistan, and Peru participated in
      individual interviews conducted on-site at one of three clinics. Interviews were
      transcribed and then coded independently and jointly. The authors used a
      qualitative analysis of interview transcripts to identify primary and secondary
      themes. RESULTS: IMGs' perceptions of the barriers to communication with their
      Appalachian patients fit into two broad themes: educational barriers and
      interpersonal barriers. Within each of these themes, the authors identified
      secondary themes: education-related barriers were science immersion and lack of
      communication training, and interpersonally related barriers were unfamiliar
      dialects, new power dynamics, and different rapport-building expectations.
      CONCLUSIONS: The analysis of the interview data yielded several important
      findings that residency programs should consider when designing orientations,
      training curricula, and communication interventions. Programs may need to address
      challenges related to regional dialect and "informal" English use, as well as
      communication barriers associated with cross-cultural differences in norms,
      values, and beliefs. Programs also need to draw on multilayered interventions to
      address the multidimensional challenges of cross-cultural physician-patient
      communication.

PMID- 19858821
TI  - Inclusion of parents in pediatric subspecialty team rounds: attitudes of the
      family and medical team.
AB  - The importance of the family's involvement in caring for children with cancer is
      as tremendous as the need to successfully educate our medical students and
      residents about the value of effective communication and family-centered care.
      This article presents a model of change undertaken by one large pediatric cancer
      center to improve family-centered care. The author describes how the inclusion of
      families in sit-down medical team rounds influenced family, medical trainee, and
      attending physician satisfaction. Despite initial reluctance from the medical
      team and early challenges, this model was found to be successful and to have
      improved the standard of care.Each morning, patients' families were given the
      opportunity to sign up to attend sit-down team rounds while their child's case
      was discussed. Participation was voluntary, and parents could ask questions and
      offer input. Together, the student, resident, fellow, family member, and
      attending formulated the treatment plan for that day.Family and trainee
      participants were surveyed for their opinions of the new style of rounds. Family
      satisfaction was unanimously improved. Medical trainees reported mixed opinions.
      Families reported increased feelings of inclusion, respect, and having a better
      understanding of their child's care. Trainees recognized the value in patient
      care and family satisfaction, but some doubted the benefit to their own training.
      Details of this change, including challenges faced, as well as the descriptive
      survey results of both the families and medical trainees, are discussed.

PMID- 19858822
TI  - The impact of senior medical students' personal difficulties on their
      communication patterns in breaking bad news.
AB  - PURPOSE: To evaluate the possible influence of personal difficulties and barriers
      that are within the news bearer and his or her self-awareness (SA) of them, on
      the patterns of communication during encounters involving breaking bad news
      (BBN). METHOD: Following an intensive BBN course in 2004, 103 senior medical
      students at the Sackler School of Medicine, Tel Aviv University, were evaluated
      for BBN competencies by the analysis of their written descriptions of how they
      visualized their manner of delivering bad news to a patient described in a
      challenging vignette. The students were further asked to reflect on their own
      difficulties and barriers that surfaced in response to reading the narrative
      presented in the vignette and in delivering the bad news. Using an immersion
      crystallization narrative analysis method, the authors analyzed the relationship
      between the students' BBN strategies and their self-perceived barriers and
      difficulties. RESULTS: Four types of communicators were identified and related to
      45 different personal and professional barriers that the students, through self
      reflection, found in themselves. These perceived barriers as well as the ability
      to self-reflect on them influenced their patterns of communication in their
      envisioned and written-down encounters, including the level of emotional
      connectedness, information provided, and the chosen focus-of-care paradigm
      (physician-centered, patient-centered, or relationship-centered). CONCLUSIONS:
      These findings empirically demonstrate that intrapersonal difficulties within the
      communicator and his or her level of SA about them influenced the manner and
      content of the communication during the encounter. This finding suggests that
      enhancing SA and addressing personal and professional difficulties could help
      physicians' capability to cope with challenging communication tasks. The authors
      propose a working tool (the Preparatory SPIKES) to facilitate the integration of
      self-reflection (by identifying personal difficulties) into day-by-day planning
      and delivery of bad news.

PMID- 19858823
TI  - Doctors' stress responses and poor communication performance in simulated bad
      news consultations.
AB  - PURPOSE: No studies have previously evaluated factors associated with high stress
      levels and poor communication performance in breaking bad news (BBN)
      consultations. This study determined factors that were most strongly related to
      doctors' stress responses and poor communication performance during a simulated
      BBN task. METHOD: In 2007, the authors recruited 24 doctors comprising 12 novices
      (i.e., interns/residents with 1-3 years' experience) and 12 experts (i.e.,
      registrars, medical/radiation oncologists, or cancer surgeons, with more than 4
      years' experience). Doctors participated in simulated BBN consultations and a
      number of control tasks. Five-minute-epoch heart rate (HR), HR variability, and
      communication performance were assessed in all participants. Subjects also
      completed a short questionnaire asking about their prior experience BBN,
      perceived stress, psychological distress (i.e., anxiety, depression), fatigue,
      and burnout. RESULTS: High stress responses were related to inexperience with
      BBN, fatigue, and giving bad versus good news. Poor communication performance in
      the consultation was related to high burnout and fatigue scores. CONCLUSIONS:
      These results suggest that BBN was a stressful experience for doctors even in a
      simulated encounter, especially for those who were inexperienced and/or fatigued.
      Poor communication performance was related to burnout and fatigue, but not
      inexperience with BBN. These results likely indicate that burnout and fatigue
      contributed to stress and poor work performance in some doctors during the
      simulated BBN task.

PMID- 19858824
TI  - Judges' perception of candidates' organization and communication, in relation to
      oral certification examination ratings.
AB  - PURPOSE: To determine (1) whether judges differed in the levels of severity they
      exercised when rating candidates' performance in an oral certification exam, (2)
      to what extent candidates' clinical competence ratings were related to their
      organization/communication ratings, and (3) to what extent clinical competence
      ratings could predict organization/communication ratings. METHOD: Six hundred
      eighty-four physicians participated in a medical specialty board's 2002 oral
      examination. Ninety-nine senior members of the medical specialty served as
      judges, rating candidates' performances. Candidates' clinical competence ratings
      were analyzed using multifaceted Rasch measurement to investigate judge severity.
      A Pearson correlation was calculated to examine the relationship between ratings
      of clinical competence and organization/communication. Logistic regression was
      used to determine to what extent clinical competence ratings predicted
      organization/communication ratings. RESULTS: There were about three statistically
      distinct strata of judge severity; judges were not interchangeable. There was a
      moderately strong relationship between the two sets of candidate ratings. Higher
      clinical competence ratings were associated with an organization/communication
      rating of acceptable, whereas lower clinical competence ratings were associated
      with an organization/communication rating of unacceptable. The judges' clinical
      competence ratings correctly predicted 61.9% of the acceptable and 88.3% of the
      unacceptable organization/communication ratings. Overall, the clinical competence
      ratings correctly predicted 80% of the organization/communication ratings.
      CONCLUSIONS: The close association between the two sets of ratings was possibly
      due to a "halo" effect. Several explanations for this relationship were explored,
      and the authors considered the implications for their understanding of how judges
      carry out this complex rating task.

PMID- 19858825
TI  - An integrated approach to evaluate faculty members' research performance.
AB  - Medical school administrations need a widely acceptable method of assessing
      research performance of faculty to make management decisions. The challenge is to
      identify metrics that allow for comparison across fields. Level of extramural
      funding, quality of publications, and peer recognition are the commonly used
      indicators of success. European institutions typically use the impact factors of
      the journals where their scientists publish, whereas U.S. institutions, including
      Mount Sinai School of Medicine (MSSM), mostly use grant funding as the major
      criterion of research productivity. At MSSM, the authors, representing the Dean's
      Office, collected data on the performance of research faculty in 2006 and 2007
      and developed a method to compare the impact factors of publications by
      individual researchers across disciplines. This was then compared with each
      individual's research density (grant funding/square foot of research space) to
      determine whether these measures correlated and whether combining them yielded
      insights different from using either one independently. Results indicated a weak
      correlation between the two metrics in 2006 data and no significant correlation
      in 2007 data. Each faculty member was plotted on a four-quadrant model on the
      basis of the impact of his or her publications and research density. This dual
      metric model allowed for the identification of the strongest and weakest
      performers and classification of those in between to develop appropriately
      tailored strategies for mentoring and development at the level of individual
      faculty. This integrated approach, based on objective numerical criteria, shows
      promise as a useful method for management of the research enterprise of medical
      schools.

PMID- 19858826
TI  - Hospitalists' involvement in pediatrics training: perspectives from pediatric
      residency program and clerkship directors.
AB  - PURPOSE: To explore the use and perceived impact of pediatric hospitalists as
      teaching attendings among pediatric residency and clerkship programs. METHOD:
      Between November 2007 and February 2008, the authors conducted a mail-based
      survey of all pediatric residency program directors (170) and pediatric clerkship
      directors (131) in the United States as identified by the Association of
      Pediatric Program Directors and Council on Medical Student Education in
      Pediatrics. The surveys focused on the responsibilities of pediatric hospitalists
      in training programs and their perceived impact on the roles of pediatric
      residents and medical students. RESULTS: The response rate for residency
      directors was 86% (146/170) and 87% (114/131) for clerkship directors. One
      hundred thirteen (77%) residency programs and 91 (80%) clerkship programs used
      hospitalists as teaching attendings. Among these programs, 65% (73) of residency
      program directors and 64% (58) of clerkship directors reported that pediatric
      hospitalists are responsible for all general inpatient services. The majority of
      residency (76%, 84) and clerkship directors (71%, 64) reported that hospitalists
      are more accessible to trainees than traditional attendings. A minority of
      residency program directors (36%, 39) reported that use of hospitalists has
      decreased senior resident autonomy. CONCLUSIONS: The role of hospitalists in
      resident and student education will likely continue to evolve over the next
      decade.Additional refinement of the roles and responsibilities of hospitalists
      will address lingering concerns in some programs about resident autonomy.

PMID- 19858827
TI  - A prospective study of the longitudinal effects of an embedded specialty
      curriculum on physical examination skills using an ophthalmology model.
AB  - PURPOSE: To prospectively evaluate effects of a longitudinal specialty curriculum
      on acquisition and retention of ophthalmic screening examination skills in a
      single class across three years of medical school (2004-2007). METHOD:
      Immediately after initial Year 2 skills training, preceptors evaluated students'
      (N=84) acquisition of basic eye screening examination skills. Similarly, the
      students self-assessed their skills. In Year 3, a required ophthalmology small
      group module during the family medicine (FM) clerkship reinforced these skills.
      The authors audited history and physicals in two Year 3 clerkships and in one
      Year 4 subinternship to evaluate charted examination performance. They
      objectively assessed simulator-based ophthalmoscopy post-FM clerkship and post
      Year 3 training. RESULTS: Preceptors rated 100% of students competent in all eye
      examination modalities post initial training; 98% of students self-rated
      themselves competent in disc visualization. An expert auditor found documented FM
      funduscopies (46%) surpassed those in a prior observational study (11%).
      Funduscopic retraining significantly improved performance on post-Year 3
      objective assessment (mean score 55% retrained versus 19% nonretrained, P=.0005).
      However, 43% of FM and 91% of internal medicine workups reflected inadequate
      overall eye evaluations. Subinternship notes documented muscle excursions in 95%
      and pupils in 71% but recorded no funduscopies. CONCLUSIONS: Additional training
      successfully reinforced skills performance, which nonetheless decayed when not
      habitually practiced. Neither physical diagnosis preceptor ratings nor excellent
      performance in the FM ophthalmology module predicted subsequent skills
      performance in other clerkships or on simulator testing. The present study
      supports a reiterative retraining model for teaching this and other specialty
      physical examination skills.

PMID- 19858828
TI  - The future of epidemiology.
AB  - In this article, the authors discuss current challenges and opportunities in
      epidemiology that will affect the field's future. Epidemiology is commonly
      considered the methodologic backbone for the fields of public health and outcomes
      research because its practitioners describe patterns of disease occurrence,
      identify risk factors and etiologic determinants, and demonstrate the usefulness
      of interventions. Like most aspects of science, epidemiology is in rapid flux.
      Several factors that are influencing and will continue to influence epidemiology
      and the health of the public include factors fundamental to framing the
      discipline of epidemiology (i.e., its means of communication, its methodologies,
      its access to data, its values, its population perspective), factors relating to
      scientific advances (e.g., genomics, comparative effectiveness in therapeutics),
      and factors shaping human health (e.g., increasing globalism, the environment,
      disease and lifestyle, demographics, infectious disease).

PMID- 19858829
TI  - AM last page: international medical education.

PMID- 19858830
TI  - Reforming health care, one unit at a time.

PMID- 19858831
TI  - The canaries in our coal mine.

PMID- 19858832
TI  - An Australian perspective.

PMID- 19858833
TI  - AJN and war.

PMID- 19858834
TI  - AJN and war.

PMID- 19858835
TI  - AJN and war.

PMID- 19858836
TI  - Health care reform.

PMID- 19858837
TI  - Unsafe injections.

PMID- 19858838
TI  - Nursing ethics.

PMID- 19858840
TI  - Nurse-led interventions decrease depression in stroke survivors.

PMID- 19858841
TI  - New York requires flu shot for health care workers.

PMID- 19858845
TI  - The electronic ICU.

PMID- 19858847
TI  - Saving SimBaby.

PMID- 19858853
TI  - Another new beginning.

PMID- 19858851
TI  - Barriers to preemptive kidney transplantation.
AB  - BACKGROUND: Patients who receive kidney transplants before beginning dialysis
      (known as preemptive transplantation) have lower rates of morbidity and mortality
      and a longer work life than do those who receive them after beginning dialysis.
      But in the United States fewer than 2.5% of patients with end-stage kidney
      disease undergo transplantation as their initial therapy. OBJECTIVE: To
      understand barriers to early transplantation, the National Kidney Foundation
      (NKF) surveyed patients randomly selected from its database. METHODS: A 28
      question survey on socioeconomic factors; perceptions, fears, and concerns about
      living-donor transplantation; and education regarding transplantation as a
      treatment option was distributed to a total of 3,586 people randomly chosen from
      the NKF's database. The database is not limited to kidney patients, and 19.3% of
      the responses were disqualified because the respondents didn't have chronic
      kidney disease (CKD) or hadn't undergone kidney transplantation. The 417
      responses acceptable for analysis represented at least 12% of qualified survey
      recipients. Of these, 316 (76%) were kidney transplant recipients from either
      living or deceased donors and 101 (24%) were patients with CKD who had never
      undergone transplantation. The surveys sent to the latter group contained slight
      modifications from those sent to the transplant recipients. We compared responses
      from people who had undergone kidney transplantation with responses from those
      who hadn't undergone the procedure. RESULTS: Renal transplant recipients had
      higher incomes and more education, were more often white, and were more likely to
      have learned about treatment options from a physician than were those who hadn't
      undergone transplantation. Half of the respondents who hadn't undergone the
      procedure believed that dialysis must precede transplantation, and 60% viewed
      transplantation as a last resort. Out-of-pocket expenses were greater for
      transplant recipients, even though worries about future medical costs were common
      in both groups. Most respondents were willing to accept a kidney from a living
      donor, although they were uncomfortable with asking someone to donate.
      CONCLUSIONS: Substantial barriers to preemptive kidney transplantation remain for
      patients with CKD; a lack of financial resources and educational deficits were
      the most common barriers found in the survey.

PMID- 19858855
TI  - Trauma in pregnancy.
AB  - Although serious trauma during pregnancy is uncommon, it remains a major cause of
      maternal and fetal death and presents a variety of patient care challenges. The
      anatomic and physiologic changes of pregnancy can affect both the nature of an
      injury and the body's response to it. Here, the author describes the mechanisms
      of traumatic injury during pregnancy, discusses the normal changes of pregnancy
      and their implications in the care of pregnant trauma patients, and offers
      strategies for assessment and treatment.

PMID- 19858857
TI  - Evidence-based practice: step by step: igniting a spirit of inquiry: an essential
      foundation for evidence-based practice.
AB  - This is the first article in a new series from the Arizona State University
      College of Nursing and Health Innovation's Center for the Advancement of Evidence
      Based Practice. Evidence-based practice (EBP) is a problem-solving approach to
      the delivery of health care that integrates the best evidence from studies and
      patient care data with clinician expertise and patient preferences and values.
      When delivered in a context of caring and in a supportive organizational culture,
      the highest quality of care and best patient outcomes can be achieved.The purpose
      of this new series is to give nurses the knowledge and skills they need to
      implement EBP consistently, one step at a time. Articles will appear every two
      months to allow you time to incorporate information as you work toward
      implementing EBP at your institution. Also, we'll schedule "Ask the Authors" call
      ins every few months to provide a direct line to the experts to help you resolve
      questions. Details about how to participate in the calls will be published with
      January's Evidence-Based Practice: Step by Step.

PMID- 19858858
TI  - Cultivating quality: shared governance supports evidence-based practice.
AB  - Blending a shared governance model with the concept of evidence-based practice
      (EBP) creates a dynamic situation for both nurses and hospitals: staff nurses are
      directly involved in improving the care they provide while growing in their
      practice and becoming more invested in their institution. Shared governance
      enables staff nurses to assume leadership roles in identifying areas for change
      and driving the change through an EBP process, while nursing leaders provide the
      tools and maintain an environment that will allow such a process to take place.

PMID- 19858859
TI  - Controlling hypertension in patients with diabetes.

PMID- 19858860
TI  - Diets vs. combinations of fat, protein, and carbohydrates.

PMID- 19858862
TI  - TeamSTEPPS.

PMID- 19858861
TI  - Drug-impregnated sponges for preventing catheter-related infections.

PMID- 19858863
TI  - Read your card, Mary Sue.

PMID- 19858864
TI  - A dynamic oral cancer field: unraveling the underlying biology and its clinical
      implication.
AB  - Oral cancer is a complex disease that is characterized by histologic and genetic
      heterogeneity. The evolution and progression of this disease is thought to result
      from the accumulation of alterations in molecular pathways. Although the oral
      cavity is accessible for routine screening of suspicious lesions, gene
      alterations are known to accrue in histologically normal tissues. Therefore, some
      cancer forerunners may remain undetected clinically or histologically. Recently
      emerging optical and molecular technologies have provided a powerful means for
      redefining the extent of the field of alteration. Often this means expanding upon
      regions detectable with standard white light approaches. In this report, we used
      a newly developed optical technique, direct fluorescence visualization, to define
      a contiguous field that extended beyond the margins of a clinically visible oral
      squamous cell carcinoma. Multiple biopsies were taken within this contiguous
      optically altered field. Genome alterations detected for each specimen were
      compared to define whether each lesion arose independently or as a consequence of
      a shared progenitor cell. Our results indicate that the field effect of oral
      cancer is extremely dynamic, with different genetic alterations present in
      different biopsies within a field. This case study also demonstrated that 2
      genetically unrelated squamous cell carcinoma could be developed within 10 mm at
      the right lateral tongue of this patient. These findings provide evidence for the
      importance to implement optical technologies in defining surgical margins and
      support the use of whole genome technologies in the diagnosis of clonal versus
      independent lesions of the oral cavity, which may have implications on treatment
      strategies.

PMID- 19858867
TI  - Lung water: what you see (with computed tomography) and what you get (with a
      bedside device).

PMID- 19858871
TI  - Anesthesia prevents auditory perceptual learning.
AB  - BACKGROUND: An auditory perceptual learning paradigm was used to investigate
      whether implicit memories are formed during general anesthesia. METHODS: Eighty
      seven patients who had an American Society of Anesthesiologists physical status
      of I-III and were scheduled to undergo an elective surgery with general
      anesthesia were randomly assigned to one of two groups. One group received
      auditory stimulation during surgery, whereas the other did not. The auditory
      stimulation consisted of pure tones presented via headphones. The Bispectral
      Index level was maintained between 40 and 50 during surgery. To assess learning,
      patients performed an auditory frequency discrimination task after surgery, and
      comparisons were made between the groups. General anesthesia was induced with
      thiopental and maintained with a mixture of fentanyl and sevoflurane. RESULTS:
      There was no difference in the amount of learning between the two groups (mean +/
      SD improvement: stimulated patients 9.2 +/- 11.3 Hz, controls 9.4 +/- 14.1 Hz).
      There was also no difference in initial thresholds (mean +/- SD initial
      thresholds: stimulated patients 31.1 +/- 33.4 Hz, controls 28.4 +/- 34.2 Hz).
      These results suggest that perceptual learning was not induced during anesthesia.
      No correlation between the bispectral index and the initial level of performance
      was found (Pearson r = -0.09, P = 0.59). CONCLUSION: Perceptual learning was not
      induced by repetitive auditory stimulation during anesthesia. This result may
      indicate that perceptual learning requires top-down processing, which is
      suppressed by the anesthetic.

PMID- 19858869
TI  - Hemoglobin-based oxygen carriers: current status and future directions.

PMID- 19858872
TI  - Age-associated changes in cardiac gene expression after preconditioning.
AB  - BACKGROUND: Cardiac protection afforded by ischemic preconditioning (IPC) and
      anesthetic preconditioning (APC) are significantly reduced in the senescent
      myocardium. The authors hypothesized that age would differentially modulate gene
      expression induced by IPC and APC in vivo. METHODS: Affymetrix RAT EXON ST 1.0
      gene chips (Affymetrix, Santa Clara, CA) were used to explore the transcriptional
      response to IPC and APC in Fisher 344 male rats (young, 3-5 months, and old, 20
      24 months, respectively). Both cohorts, young and old, were divided into three
      groups: (1) sham control, (2) IPC, and (3) APC. After a total of 90 min, the
      heart was removed, and the total RNA and protein were extracted. RESULTS: Thirty
      one transcripts were increased in the young animals subjected to IPC,
      particularly transcriptional regulators (Atf3, Egr-1, Btg2, Egr2), cytokines
      (interleukin 6, CSF1, Myd88), chemokines (Cxcl10, Ccl2, Ccl7), regulators of
      growth and inflammation (Reg3g, Hamp), remodeling and cell adhesion migration
      (Cyr61, Tfpi2, Timp1), regulators of apoptosis/cell death (Birc3, Arntl, Hamp,
      Phlda1), and cell cycle control/DNA repairs (Rrad, Gadd45b, Gadd45g). In
      contrast, only one transcript increased (Atf3) in the old animals subjected to
      IPC. No changes in gene expression were found in the young or the old animals
      subjected to APC. CONCLUSIONS: Early-phase IPC and APC induced different genomic
      responses. The absence of detectable changes associated with early-phase APC
      suggests a posttranscriptional or posttranslational mechanism. The absence of a
      genomic response in the senescent myocardium (except for IPC-induced Atf3) could
      underlie the failure of IPC to provide any cardiac protective benefit to older
      animals.

PMID- 19858874
TI  - Mathematical modeling of the pain and progress of the first stage of nulliparous
      labor.
AB  - BACKGROUND: Patient characteristics may contribute to the progress and pain of
      labor. Quantitative evaluation of the effects of patient characteristics requires
      robust mathematical models of labor progress and labor pain. METHODS: The authors
      retrospectively studied 100 sequential deliveries from each of five self-reported
      ethnic groups (Asian, Black, Hispanic, Other, and White). Demographic variables,
      cervical dilation, and numerical rating scores for pain before analgesia and
      cervical dilation were abstracted from the automated medical record. Labor
      progress was modeled with a biexponential function describing the latent and
      active phases of labor. Labor pain was modeled as a sigmoid function of cervical
      dilation by using a previously validated mathematical model. The covariates,
      including self-described ethnicity, were analyzed with NONMEM. RESULTS: The
      biexponential function described the time course of labor progress better than
      several alternative functions, including the sigmoidal function introduced by
      Friedman. The sigmoidal function of labor pain described its dynamic nature well,
      with substantial intersubject variability. Asian women had slower active labor
      than other ethnicities (P < 0.01). Asian women also reported less pain during
      their labor compared to all other patients (P < 0.001). Slower labor progress was
      associated with less rapid progression of pain, but this did not obviate the
      effect of Asian ethnicity on pain. Neuraxial analgesia is strongly associated
      with slower labor (P < 0.0001). Greater maternal weight was associated with
      slower active labor (P < 0.0001). CONCLUSIONS: Mathematical models can be used to
      detect subtle effects of patient covariates on the progress and pain of the first
      stage of labor. Asian women and heavier women had slower labor and slower onset
      of labor pain than others. These effects were modest compared with the
      substantial remaining unexplained subject-to-subject variability in labor
      progress and labor pain.

PMID- 19858877
TI  - Anaphylaxis and anesthesia: controversies and new insights.

PMID- 19858878
TI  - Balancing the force of direct laryngoscopy with manual in-line stabilization.

PMID- 19858875
TI  - Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase
      in the duration of thermal antinociception in sciatic nerve block in rat.
AB  - BACKGROUND: The current study was designed to test the hypothesis that
      dexmedetomidine added to ropivacaine would increase the duration of
      antinociception to a thermal stimulus in a dose-dependent fashion in a rat model
      of sciatic nerve blockade. METHODS: Fifty adult Sprague-Dawley rats (10
      rats/group) received unilateral sciatic nerve blocks with 0.2 ml ropivacaine
      (0.5%) or 0.2 ml ropivacaine (0.5%) plus dexmedetomidine (2.7 microm [0.5
      microg/kg], 11.7 microm [2 microg/kg], 34.1 microm [6 microg/kg], or 120.6 microm
      [20 microg/kg]) in a randomized, blinded fashion. Time to paw withdrawal latency
      to a thermal stimulus for both paws and an assessment of motor function were
      measured every 30 min after the nerve block until a return to baseline. RESULTS:
      Dexmedetomidine added to ropivacaine increased the duration of dense sensory
      blockade and time for return to normal sensory function in a dose-dependent
      fashion (P < 0.005). There was a significant time (P < 0.005), dose (P < 0.005),
      and time-by-dose effect (P < 0.005) on paw withdrawal latencies of the operative
      paws. There were no significant differences in paw withdrawal latencies of the
      control paws, indicating little systemic effect of the dexmedetomidine. The
      duration of motor blockade was also increased with dexmedetomidine. High-dose
      dexmedetomidine (120.6 mum) was not neurotoxic. CONCLUSION: This is the first
      study showing that dexmedetomidine added to ropivacaine increases the duration of
      sensory blockade in a dose-dependent fashion in rats. The findings are an
      essential first step encouraging future efficacy studies in humans.

PMID- 19858879
TI  - Importance of clinical relevance in clinical trials.

PMID- 19858882
TI  - All glucose measurements are not equal.

PMID- 19858883
TI  - Professionalism considerations.

PMID- 19858884
TI  - Role of p75 neurotrophin receptor in isoflurane-mediated neuronal changes.

PMID- 19858888
TI  - Difficult mask ventilation and neuromuscular blockade.

PMID- 19858889
TI  - Anesthesia-related mortality.

PMID- 19858890
TI  - Are signposts in the woods pointing in the right direction?

PMID- 19858892
TI  - Concerns regarding ultrasound-guided regional anesthesia.

PMID- 19858894
TI  - Green breast milk after propofol administration.

PMID- 19858895
TI  - Bibliography--Editors' selection of current world literature.

PMID- 19858896
TI  - Notes from the Board: President's Message.

PMID- 19858897
TI  - Where is the link to nursing?

PMID- 19858898
TI  - Millennials and their value cohort: how to educate them.

PMID- 19858899
TI  - Bird flu, swine flu, and resistant influenza: the scary development of antiviral
      resistant strains-part 2: novel A(H1N1): the flu we never expected.

PMID- 19858900
TI  - Describing saline-lock usage patterns on a telemetry unit: a retrospective study.
AB  - PURPOSE/OBJECTIVES: The purpose of this study was to describe saline-lock (SL)
      usage patterns of patients admitted with high-frequency medical diagnoses to a
      telemetry unit and to determine the acceptability of constructing a decision tree
      stratifying SL insertion decisions. DESIGN: A quantitative, descriptive study
      using retrospective chart reviews was used. SETTING: The study was conducted
      within a 48-bed telemetry unit of a large, urban, teaching hospital. SAMPLE: The
      sample was composed of the medical records of patients admitted to the telemetry
      unit from April 2007 through June 2007. Charts were included in the sample if the
      patient was admitted to the telemetry unit with one of the 4 highest-frequency
      admitting diagnoses, specifically myocardial infarction, congestive heart
      failure, syncope, and chest pain. METHODS: Data were collected via patient chart
      review using an electronic database by a team of 4 registered nurses, including 1
      clinical nurse specialist. Data collection steps included a verification process
      that involved a random audit of the most recently collected chart data. FINDINGS:
      More than one-third of SLs were not used, and more than half that were used were
      accessed for the nonurgent delivery of medications. Saline locks were most
      frequently used for urgent medication delivery when patients were admitted with a
      diagnosis of heart failure. CONCLUSIONS: Findings suggest that most patients
      admitted to telemetry units do not require an immediate intravenous access for
      drug delivery. IMPLICATIONS: Clinical nurse specialists should consider that an
      evidence-based algorithm for determining SL need may improve patient outcomes and
      reduce SL-associated complication and infection rates.

PMID- 19858901
TI  - Clinical nurse specialists driving research and practice through Research
      Roundtables.
AB  - Providing patient care based on the best evidence is a priority for healthcare
      institutions across the country to improve practice and patient outcomes.
      Creating a culture of evidence-based practice (EBP) within an organization can be
      a challenging task. Literature has identified numerous barriers to EBP including
      negative attitudes and perceptions among nurses and lack of organizational
      support, time, resources, and confidence with these skills. Creating programs
      that help nurses appreciate the value and importance of nursing research for
      practice can be an effective approach in changing the culture. Research
      Roundtable is a collaborative partnership between a healthcare system and a
      baccalaureate nursing program to promote EBP and research skills in nurses and
      nursing students. Initial goals of the program focused on increasing the nurses'
      knowledge base of the research process and applying research to actual clinical
      problems. Over the course of 3 years, Roundtable evolved from development and
      implementation of research projects to concentrating on the identification of
      clinical problems that could be analyzed and solved through the use of EBP
      processes. The program has resulted in the completion of research studies,
      implementation of practice changes based on evidence uncovered in group work, and
      the approval of research projects in data collection phases. The positive impacts
      of Roundtable have been identified at the level of the staff nurse and the
      organization as a whole. This article describes the role of the clinical nurse
      specialist in the development and implementation of the Research Roundtable.

PMID- 19858902
TI  - The clinical nurse specialist as change agent: reducing employee injury and
      related costs.
AB  - PURPOSE: The purpose of this study was, first, to examine the role of the
      clinical nurse specialist (CNS) as it relates to the implementation of a CNS
      initiated Safe Movement Program and, second, to report findings from a CNS
      initiated safe movement program (SMP) in reducing healthcare workers' injuries
      and related costs. DESIGN: A longitudinal preimplementation and
      postimplementation study design was used. SETTING: Healthcare workers in a 156
      bed, extended-care facility (nursing home) participated in the study. SAMPLE:
      Participants at the onset of the study included 52 healthcare workers who
      participated in the study preimplementation and postimplementation of the SMP.
      Attrition resulted in a final sample of 46. METHODS: Data were collected on
      healthcare workers' perceptions of injuries as well as existing incident reports
      and workers' compensation records preimplementation and postimplementation of the
      study. FINDINGS: Outcomes included major reduction in healthcare worker injuries
      and related workers' compensation cost savings. The number of healthcare workers
      who thought an injury occurred as a result of lifting or transferring a resident
      was reduced by 75%, and perceptions of lifting and transfer injuries resulting in
      a back strain were reduced by 80%. The number of times in a month healthcare
      workers felt lifting or transferring a resident was "too much" for them was
      reduced by 73%. Workers' compensation insurance was reduced by 93%. CONCLUSIONS:
      A CNS-initiated SMP reduces injuries and costs and may recoup the cost of the
      program in 5 years. IMPLICATIONS: Job-related musculoskeletal injuries are a
      critical problem. As the healthcare workforce continues to age, a comprehensive
      SMP needs to be implemented to ensure safety of employees in the clinical
      practice setting. The program may pay for itself in 5 years.

PMID- 19858904
TI  - Nurses' knowledge of Advance Directives, Patient Self-determination Act, and
      Illinois Advance Directive Law.
AB  - The purpose of this cross-sectional survey was to describe the level of knowledge
      and education nurses receive on advance directives (ADs), the Patient Self
      determination Act, and Illinois state law. A modified version of the Knowledge
      Attitudinal-Experiential Survey on Advance Directives was used with a convenience
      sample of 110 nurses from general medical-surgical, rehabilitation, oncology,
      intensive care unit, and recovery units in a medical center in Illinois. Results
      suggested that respondents were somewhat knowledgeable about general AD items,
      but less knowledgeable about the Patient Self-determination Act and Illinois
      state law. Clearly, nurses need further education regarding rules and regulations
      concerning Illinois law on ADs.

PMID- 19858905
TI  - The role of systematic reviews in teaching evidence-based practice.

PMID- 19858906
TI  - Clinical nurse specialist profile.

PMID- 19858907
TI  - Stewardship and hope: the story of a tree.

PMID- 19858909
TI  - Bibliography. Current world literature.

PMID- 19858911
TI  - Current world literature.

PMID- 19858914
TI  - Reflects on the eve of reform.

PMID- 19858915
TI  - Identifying organizational cultures that promote patient safety.
AB  - BACKGROUND: Safety climate refers to shared perceptions of what an organization
      is like with regard to safety, whereas safety culture refers to employees'
      fundamental ideology and orientation and explains why safety is pursued in the
      manner exhibited within a particular organization. Although research has sought
      to identify opportunities for improving safety outcomes by studying patterns of
      variation in safety climate, few empirical studies have examined the impact of
      organizational characteristics such as culture on hospital safety climate.
      PURPOSE: This study explored how aspects of general organizational culture relate
      to hospital patient safety climate. METHODOLOGY: In a stratified sample of 92
      U.S. hospitals, we sampled 100% of senior managers and physicians and 10% of
      other hospital workers. The Patient Safety Climate in Healthcare Organizations
      and the Zammuto and Krakower organizational culture surveys measured safety
      climate and group, entrepreneurial, hierarchical, and production orientation of
      hospitals' culture, respectively. We administered safety climate surveys to
      18,361 personnel and organizational culture surveys to a 5,894 random subsample
      between March 2004 and May 2005. Secondary data came from the 2004 American
      Hospital Association Annual Hospital Survey and Dun & Bradstreet. Hierarchical
      linear regressions assessed relationships between organizational culture and
      safety climate measures. FINDINGS: Aspects of general organizational culture were
      strongly related to safety climate. A higher level of group culture correlated
      with a higher level of safety climate, but more hierarchical culture was
      associated with lower safety climate. Aspects of organizational culture accounted
      for more than threefold improvement in measures of model fit compared with models
      with controls alone. A mix of culture types, emphasizing group culture, seemed
      optimal for safety climate. PRACTICE IMPLICATIONS: Safety climate and
      organizational culture are positively related. Results support strategies that
      promote group orientation and reduced hierarchy, including use of
      multidisciplinary team training, continuous quality improvement tools, and human
      resource practices and policies.

PMID- 19858916
TI  - From a blame culture to a just culture in health care.
AB  - BACKGROUND: A prevailing blame culture in health care has been suggested as a
      major source of an unacceptably high number of medical errors. A just culture has
      emerged as an imperative for improving the quality and safety of patient care.
      However, health care organizations are finding it hard to move from a culture of
      blame to a just culture. PURPOSE: We argue that moving from a blame culture to a
      just culture requires a comprehensive understanding of organizational attributes
      or antecedents that cause blame or just cultures. Health care organizations need
      to build organizational capacity in the form of human resource (HR) management
      capabilities to achieve a just culture. METHODOLOGY: This is a conceptual
      article. Health care management literature was reviewed with twin objectives: (a)
      to ascertain if a consistent pattern existed in organizational attributes that
      lead to either blame or just cultures and (2) to find out ways to reform a blame
      culture. CONCLUSIONS: On the basis of the review of related literature, we
      conclude that (a) a blame culture is more likely to occur in health care
      organizations that rely predominantly on hierarchical, compliance-based
      functional management systems; (b) a just or learning culture is more likely to
      occur in health organizations that elicit greater employee involvement in
      decision making; and (c) human resource management capabilities play an important
      role in moving from a blame culture to a just culture. PRACTICE IMPLICATIONS:
      Organizational culture or human resource management practices play a critical
      role in the health care delivery process. Health care organizations need to
      develop a culture that harnesses the ideas and ingenuity of health care
      professional by employing a commitment-based management philosophy rather than
      strangling them by overregulating their behaviors using a control-based
      philosophy. They cannot simply wish away the deeply entrenched culture of blame
      nor can they outsource their way out of it. Health care organizations need to
      build internal human resource management capabilities to bring about the
      necessary changes in their culture and management systems and to become learning
      organizations.

PMID- 19858917
TI  - Nursing teamwork, staff characteristics, work schedules, and staffing.
AB  - PURPOSE: This study aimed to explore whether and how staff characteristics,
      staffing, and scheduling variables are associated with the level of teamwork in
      nursing staff on acute care hospital patient units. DESIGN: This was a cross
      sectional study with a sample of 1,758 nursing staff members from two different
      hospitals on 38 patient care units who completed the Nursing Teamwork Survey in
      2008. This study focused on nursing teams who are stationed on a particular
      patient care unit (as opposed to visitors to the units). The return rate was
      56.9%. The sample was made up of 77.4% nurses (registered nurses and licensed
      practical nurses), 11.9% assistive personnel, and 7.9% unit secretaries.
      FINDINGS: Teamwork varied by unit and service type, with the highest scores
      occurring in pediatrics and maternity and the lowest scores on the medical
      surgical and emergency units. Staff with less than 6 months of experience, those
      working 8- or 10-hour shifts (as opposed to 12 hours or a combination of 8 and 12
      hours), part-time staff (as opposed to full time), and those working on night
      shift had higher teamwork scores. The higher teamwork scores were also associated
      with no or little overtime. The higher perception of the adequacy of staffing and
      the fewer patients cared for on a previous shift, the higher the teamwork scores.
      CONCLUSIONS: There is a relationship between selected staff characteristics,
      aspects of work schedules, staffing, and teamwork. Nursing staff want to work
      where teamwork is high, and perceptions of good staffing lead to higher teamwork.
      Higher teamwork scores correlated with those who worked less overtime.

PMID- 19858918
TI  - Improving work environments in health care: test of a theoretical framework.
AB  - BACKGROUND: In light of high levels of staff turnover and variability in the
      quality of health care, much attention is currently being paid to the health care
      work environment and how it potentially relates to staff, patient, and
      organizational outcomes. Although some attention has been paid to staffing
      variables, more attention must be paid to improving the work environment for
      patient care. PURPOSES: The purpose of this study was to empirically explore a
      theoretical model linking the work environment in the health care setting and how
      it might relate to work engagement, organizational commitment, and patient
      safety. This study also explored how the work environment influences staff
      psychological safety, which has been show to influence several variables
      important in health care. METHODOLOGY: Clinical care providers at a large
      metropolitan hospital were surveyed using a mail methodology. The overall
      response rate was 42%. This study analyzed perceptions of staff who provided
      direct care to patients. FINDINGS: Using structural equation modeling, we found
      that different dimensions of the work environment were related to different
      outcome variables. For example, a climate for continuous quality improvement was
      positively related to organizational commitment and patient safety, and
      psychological safety partially mediated these relationships. Patient-centered
      care was positively related to commitment but negatively related to engagement.
      PRACTICE IMPLICATIONS: Health care managers need to examine how organizational
      policies and practices are translated into the work environment and how these
      influence practices on the front lines of care. It appears that care provider
      perceptions of their work environments may be useful to consider for improvement
      efforts.

PMID- 19858919
TI  - Models of consumer value cocreation in health care.
AB  - BACKGROUND: In recent years, consumer participation in health care has gained
      critical importance as health care organizations (HCOs) seek varied avenues to
      enhance the quality and the value of their offerings. Many large HCOs have
      established online health communities where health care consumers (patients) can
      interact with one another to share knowledge and offer emotional support in
      disease management and care. Importantly, the focus of consumer participation in
      health care has moved beyond such personal health care management as the
      potential for consumers to participate in innovation and value creation in varied
      areas of the health care industry becomes increasingly evident. Realizing such
      potential, however, will require HCOs to develop a better understanding of the
      varied types of consumer value cocreation that are enabled by new information and
      communication technologies such as online health communities and Web 2.0 (social
      media) technologies. PURPOSES: This article seeks to contribute toward such an
      understanding by offering a concise and coherent theoretical framework to analyze
      consumer value cocreation in health care. We identify four alternate models of
      consumer value cocreation-the partnership model, the open-source model, the
      support-group model, and the diffusion model-and discuss their implications for
      HCOs. METHOD: We develop our theoretical framework by drawing on theories and
      concepts in knowledge creation, innovation management, and online communities. A
      set of propositions are developed by combining theoretical insights from these
      areas with real-world examples of consumer value cocreation in health care.
      FINDINGS: The theoretical framework offered here informs on the potential impact
      of the different models of consumer value cocreation on important organizational
      variables such as innovation cost and time, service quality, and consumer
      perceptions of HCO. PRACTICE IMPLICATIONS: An understanding of the four models of
      consumer value cocreation can help HCOs adopt appropriate strategies and
      practices to embrace consumers as partners in the development and delivery of
      innovative health care products and services.

PMID- 19858920
TI  - A theoretical framework for shedding additional light on the determinants of
      medical practice value.
AB  - BACKGROUND: Over the years, business valuation techniques have been widely used
      to appraise the financial worth of medical practices. However, it has been argued
      that medical practices are one of the most complex and difficult types of
      business enterprises to value. PURPOSE: The purpose of the current study is to
      develop a theoretical framework that sheds additional light on the determinants
      of a medical practice's value and to provide practitioners with a theory-based
      model on which to base valuations to avoid "wild west" scenarios where individual
      valuators use his or her own unique models that can lead to wild variations in
      the value amount of the same medical practice. APPROACH: The article starts by
      discussing standard approaches to valuing any business including medical
      practices. We then develop a theoretical framework that sheds additional light on
      the determinants of a medical practice's value by showing how strategic choice
      and environmental determinism affect the value of a medical practice. Once the
      framework is developed, the practice implications related to the framework are
      discussed. FINDINGS: In this article, determinants of a medical practice's
      potential for sustained profitability are identified. Specifically, a framework
      is presented that shows how the combination of strategic choice and environmental
      determinism can affect a medical practice's chances of sustained profitability.
      Developing such a framework is an important contribution to the literature given
      that one of the most problematic areas of medical practice valuation is
      determining the factors that a valuator must assess to arrive at an appropriate
      fair market value for a practice. PRACTICE IMPLICATIONS: The development of a
      framework that sheds additional light on the determinants of a medical practice's
      value is important in light of the difficulty of obtaining reliable market data
      regarding sales of medical practices, which tend to be closely held private
      entities.

PMID- 19858921
TI  - The role of information technology usage in physician practice satisfaction.
AB  - BACKGROUND: Despite the growing use of information technology (IT) in medical
      practices, little is known about the relationship between IT and physician
      satisfaction. PURPOSE: The objective of this study was to examine the
      relationship between physician IT adoption (of various applications) and overall
      practice satisfaction, as well as satisfaction with the level of computerization
      at the practice. METHODS: Data from a Florida survey examining physicians' use of
      IT and satisfaction were analyzed. Odds ratios (ORs), adjusted for physician
      demographics and practice characteristics, were computed utilizing logistic
      regressions to study the independent relationship of electronic health record
      (EHR) usage, PDA usage, use of e-mail with patients, and the use of disease
      management software with satisfaction. In addition, we examined the relationship
      between satisfaction with IT and overall satisfaction with the current medical
      practice. RESULTS: In multivariate analysis, EHR users were 5 times more likely
      to be satisfied with the level of computerization in their practice (OR = 4.93,
      95% CI = 3.68-6.61) and 1.8 times more likely to be satisfied with their overall
      medical practice (OR = 1.77, 95% CI = 1.35-2.32). PDA use was also associated
      with an increase in satisfaction with the level of computerization (OR = 1.23,
      95% CI = 1.02-1.47) and with the overall medical practice (OR = 1.30, 95% CI =
      1.07-1.57). E-mail use with patients was negatively related to satisfaction with
      the level of computerization in the practice (OR = 0.69, 95% CI = 0.54-0.90).
      Last, physicians who were satisfied with IT were 4 times more likely to be
      satisfied with the current state of their medical practice (OR = 3.97, 95% CI =
      3.29-4.81). IMPLICATIONS: Physician users of IT applications, especially EHRs,
      are generally satisfied with these technologies. Potential adopters and/or policy
      makers interested in influencing IT adoption should consider the positive impact
      that computer automation can have on medical practice.

PMID- 19858922
TI  - International perspectives on backsourcing in health: is it just a merry-go
      round?
AB  - BACKGROUND: Outsourcing in health was increasingly used in the 1990s as
      managerialism was adopted across the Italian and Australian public sectors. Many
      reasons have been given for outsourcing, such as focusing on core competencies,
      reducing costs and improving efficiency, reducing risk, and improving the
      management of labor, to name a few. Notwithstanding this, some health
      organizations have moved to backsourcing. PURPOSES OF THE STUDY: This research
      aimed to contribute to the debate and literature on managerial practices in
      health care by analyzing the extent of backsourcing in public health in Italy and
      Australia, the reasons, and expected benefits and criticalities. METHODOLOGY: To
      achieve the research objectives, a questionnaire was developed, and after a pilot
      test, it was mailed out to all Italian and Australian public providers. The
      questionnaire had 10 questions. Most of the responses were indicated on a 5-point
      Likert-type scale. Descriptive analysis was performed, such as obtaining mean and
      standard deviation. FINDINGS: The total response rate was 46% in Italy and 29% in
      Australia. Results showed that nearly 15% of the Italian and 30% of the
      Australian health care providers had backsourced. In both countries, a lack of
      complete satisfaction with outsourcing was reported. When backsourcing did occur
      in Italy, it was due to more freedom becoming available in hiring personnel,
      whereas in Australia, it was due to quality issues with outsourcing.
      IMPLICATIONS: Outsourcing can be considered to be an important tool that health
      care management may use to reach their objectives, but often, similar objectives
      are in place for backsourcing. This managerial learning-by-doing process seemed
      to emerge based on past results rather than a clear understanding of the
      environment and critical evaluation of criticalities prior to the event.

PMID- 19858924
TI  - Increased peripheral proinflammatory cytokines in HIV-1-infected patients with
      prolonged viral suppression suffering from high psychological stress.

PMID- 19858925
TI  - Ribavirin plasma concentration predicts sustained virological response to
      peginterferon Alfa 2a plus ribavirin in previously treated HCV-HIV-coinfected
      patients.

PMID- 19858926
TI  - Tenofovir coadministration is not associated with lower unboosted atazanavir
      plasma exposure in the clinical setting.

PMID- 19858927
TI  - Health systems exist for real people. Introduction.

PMID- 19858928
TI  - Lessons learned from PEPFAR.
AB  - The United States President's Emergency Plan for AIDS Relief (PEPFAR), launched
      by President Bush with strong bipartisan support, was a historic moment in
      development both in size and scope. With $18.8 billion across its first 5 years,
      it is the largest international health initiative in history for a specific
      disease. In scope, it is the first global initiative to tackle a chronic disease
      and was based in a new philosophical foundation centered in country ownership, a
      results-based accountable approach, the engagement of all sectors, and good
      governance. With resources and a strong intellectual base, PEPFAR saved lives and
      provided lessons learned for effective development.

PMID- 19858929
TI  - Scaling up antiretroviral therapy in Malawi-implications for managing other
      chronic diseases in resource-limited countries.
AB  - The national scale-up of antiretroviral therapy (ART) in Malawi is based on the
      public health approach, with principles and practices borrowed from the
      successful DOTS (directly observed treatment, short course) tuberculosis control
      framework. The key principles include political commitment, free care, and
      standardized systems for case finding, treatment, recording and reporting, and
      drug procurement. Scale-up of ART started in June 2004, and by December 2008,
      223,437 patients were registered for treatment within a health system that is
      severely underresourced. The Malawi model for delivering lifelong ART can be
      adapted and used for managing patients with chronic noncommunicable diseases, the
      burden of which is already high and continues to grow in low-income and middle
      income countries. This article discusses how the principles behind the successful
      Malawi model of ART delivery can be applied to the management of other chronic
      diseases in resource-limited settings and how this paradigm can be used for
      health systems strengthening.

PMID- 19858930
TI  - Impact of HIV prevention programs on drug users in Malaysia.
AB  - Faced with a rising HIV epidemic among injecting drug users, harm reduction
      policies and programs were introduced in Malaysia in 2005. The positive impact
      seen since the introduction of these programs comprise the inclusion of the
      health aspects of illicit drug use in the country's drug policies; better access
      to antiretroviral therapy for injecting drug users who are HIV infected;
      reduction in HIV-risk behavior; and greater social benefits, including increased
      employment. Despite these achievements, tension between law enforcement and
      public health persists, as harm reduction exists alongside an overall drug policy
      that is based on abstinence and zero tolerance. Unless there is harmonization of
      this policy, sustainability and scale-up of harm reduction programs will remain a
      challenge.

PMID- 19858931
TI  - The role of nonphysician clinicians in the rapid expansion of HIV care in
      Mozambique.
AB  - The shortage of health workers impedes universal coverage of quality HIV
      services, especially in those countries hardest hit by the epidemic. The dramatic
      increase in international aid to scale-up HIV services, including antiretroviral
      therapy (ART), has highlighted workforce deficiencies and provided an opportunity
      to strengthen health systems capacity. In Mozambique, a country with a high HIV
      burden and a staggering workforce deficit, the Ministry of Health looked to past
      experience in workforce expansion to rapidly build ART delivery capacity,
      including reliance on existing nonphysician clinicians (NPC) to prescribe ART and
      dramatically increasing the output of NPC training. As a result of responsible
      task shifting, the number of facilities providing ART tripled during a 6-month
      period, and patients from disadvantaged areas have access to quality ART
      services. Because the NPC-driven ART approach is integrated into primary health
      care, the addition of new clinical staff also promises to improve general health
      services.

PMID- 19858932
TI  - Lessons from Harlem: Relevance to a global epidemic.
AB  - The HIV epidemic has challenged health systems around the world, including those
      in resource-rich countries. In Harlem, a disenfranchised community in New York
      City, poverty, mistrust of health care providers, and a frail health care system
      ill equipped to handle a chronic disease with profound psychosocial elements
      challenged the ability to mount an effective response to HIV. A step-by-step
      effort, initially conceptualized as an emergency response, was followed by a
      systematic approach to strengthen the health system and shape it to address the
      unique characteristics of the disease and the needs of the community. Lessons
      learned from this effort have been applied to other health threats in the
      community and could inform the global response to HIV.

PMID- 19858933
TI  - The impact of HIV scale-up on the role of nurses in South Africa: Time for a new
      approach.
AB  - South Africa's health care system is struggling to respond to the devastating
      impact of HIV/AIDS while at the same time respecting its postapartheid mandate to
      provide equitable health services to all. These unprecedented challenges are
      forcing a rethinking and reorganization of health resources and systems and a
      reappraisal of the role of nurses in the care of complex and chronic illness.
      Increasingly, the scale-up of HIV services is being reconceptualized to match
      both the urgent need for prevention, care, and treatment and the national vision
      of decentralized primary health care. HIV scale-up has triggered innovations in
      nurse training, task shifting, retention, and scope of practice that need not
      remain HIV specific. Lessons learned in the context of HIV have the potential to
      enhance nursing practice and human resources for health more generally,
      strengthening South Africa's health systems and improving access to effective
      health services.

PMID- 19858935
TI  - Developing laboratory systems and infrastructure for HIV scale-up: A tool for
      health systems strengthening in resource-limited settings.
AB  - The rapid scale-up of HIV care and treatment in resource-limited settings has
      overwhelmed many public health laboratory services already burdened with human
      resource shortages, an aging and inadequate infrastructure, and a lack of quality
      systems. There is, however, a growing appreciation of the opportunity to use HIV
      related laboratory strengthening as means to strengthen health systems in
      general. We briefly describe ongoing efforts to integrate HIV laboratory support
      into HIV care and treatment systems, thereby strengthening laboratory systems in
      support of both HIV scale-up and overall health systems strengthening.

PMID- 19858934
TI  - Global HIV/AIDS funding and health systems: Searching for the win-win.
AB  - Donors, developing country governments, and NGOs are searching for ways to use
      funding for HIV/AIDS programs that strengthen the functioning of weak health
      systems. This is motivated both by the realization that a large share of donor
      funding for global health is and will continue to be dedicated to HIV/AIDS, and
      that the aims of more and better treatment, prevention, and care can be achieved
      only with attention to systemic capacities. For AIDS resources to strengthen
      health systems, decision makers should: (a) mitigate the risks that AIDS spending
      may weaken the ability of health systems to respond to other health problems; (b)
      find ways for procurement, supply chain, management information, and other
      systems that are created to support AIDS treatment to be broadened to serve other
      types of services; and (c) build upon the ways in which AIDS programs have
      overcome some demand-side barriers to use of services. In pursuing this agenda,
      donors should recognize that health system development is a function of the
      national and local political economy and place respect for national sovereignty
      as a central tenet of their policies and practices.

PMID- 19858936
TI  - How AIDS funding strengthens health systems: progress in pharmaceutical
      management.
AB  - In recent years, new global initiatives responding to the AIDS crisis have
      dramatically affected-and often significantly improved-how developing countries
      procure, distribute, and manage pharmaceuticals. A number of developments related
      to treatment scale-up, initially focused on AIDS-related products, have created
      frameworks for widening access to medicines for other diseases that
      disproportionally impact countries with limited resources and for strengthening
      health systems overall. Examples of such systems strengthening have come in the
      areas of drug development and pricing; policy and regulation; pharmaceutical
      procurement, distribution, and use; and management systems, such as for health
      information and human resources. For example, a hospital in South Africa
      developed new tools to decentralize provision of antiretroviral therapy to local
      clinics-bringing treatment closer to patients and shifting responsibility from
      scarce pharmacists to lower level pharmacy staff. Successful, the system was
      expanded to patients with other chronic conditions, such as mental illness.
      Progress toward universal access to HIV prevention, treatment, care, and support
      will continue the push to strengthen pharmaceutical sectors that serve not only
      HIV-related needs but all health needs; health experts can likely take these
      achievements further to maximize their expansion into the wider health system.

PMID- 19858937
TI  - International health financing and the response to AIDS.
AB  - Efforts to finance HIV responses have generated large increases in funding,
      catalyzed activism and institutional innovation, and brought renewed attention to
      health issues and systems. The benefits go well beyond HIV programs. The
      substantial increases in HIV funding are a tiny percentage of overall increases
      in health financing, with other areas also seeing large absolute increases. Data
      on health funding suggest an improved "pro-poor" distribution, with Africa
      benefiting relatively more from increased external flows. A literature review
      found few evidence-based analyses of the impact of AIDS programs and funding on
      broader health financing. Conceptual frameworks that would facilitate such
      analysis are summarized.

PMID- 19858938
TI  - Has aid for AIDS raised all health funding boats?
AB  - Global health analysts have debated whether donor prioritization of HIV/AIDS
      control has lifted all boats, raising attention and funding levels for health
      issues aside from HIV/AIDS. We investigate this question, considering donor
      funding for 4 historically prominent health agendas-HIV/AIDS, health systems
      strengthening, population and reproductive health, and infectious disease control
      over the decade 1998-2007. We employ funding data from the Development Assistance
      Committee of the Organization for Economic Cooperation and Development, which
      tracks donor aid. The data indicate that HIV/AIDS may have helped to increase
      funding for the control of other infectious diseases; however, there is no firm
      evidence that other health issues beyond the control of infectious diseases have
      benefited. Between 1998 and 2007, funding for HIV/AIDS control rose from just
      5.5% to nearly half of all aid for health. Over the same period, funding for
      health systems strengthening declined from 62.3% to 23.9% of total health aid and
      that for population and reproductive health declined from 26.4% to 12.3%. Also,
      even as total aid for health tripled during this decade, aid for health systems
      strengthening largely stagnated. Overall, the data indicate little support for
      the contention that donor funding for HIV/AIDS has lifted all boats.

PMID- 19858939
TI  - Civil society, political mobilization, and the impact of HIV scale-up on health
      systems in Brazil.
AB  - This article examines the role of civil society in shaping HIV and AIDS policies
      and programs in Brazil. It focuses on the historical context of the
      redemocratization of Brazilian society during the 1980s, when the initial
      response to the epidemic took shape, and emphasizes the role of social movements
      linked to the progressive Catholic Church, the sanitary reform movement in public
      health, and the emerging gay rights movement in the early response to the
      epidemic in Brazil. It highlights the broad-based civil society coalition that
      took shape over the course of the 1990s and the political alliances that were
      built up shortly after the 1996 International AIDS Conference in Vancouver,
      Canada, to pass legislation guaranteeing the right to access to antiretroviral
      treatment. It emphasizes the continued importance of civil society organizations
      in particular, AIDS-related nongovernmental organizations-and leading AIDS
      activists in exerting continued pressure to guarantee the sustainability of
      treatment access and the impact that action focused on HIV and AIDS has had on
      the Brazilian public health system more broadly, particularly through
      strengthening health infrastructures and providing a model for health-related
      social mobilization.

PMID- 19858940
TI  - Impact of HIV treatment scale-up on women's reproductive health care and
      reproductive rights in Southern Africa.
AB  - The HIV epidemic has changed the face of women's reproductive health across
      southern Africa. In some circles, there have been calls for restrictions on
      women's reproductive rights, focusing particularly on the spread of HIV between
      sexual partners and from mother to child. However, during the past decade, public
      health attention and resources for the clinical care of HIV-infected individuals
      living in Africa have led to advances in women's reproductive health services. As
      many programs have recognized that effective HIV care and treatment services must
      link to other areas of primary care, key reproductive health services such as
      those providing contraception and barrier methods are commonly integrated into
      antiretroviral therapy services. In much of the region, this programmatic focus
      has helped increase attention on the ground to women's reproductive rights.
      However, in many settings, policies explicitly supporting the reproductive rights
      of HIV-infected women have lagged. Important gaps remain both in policy
      development and in the design, evaluation, and implementation of interventions
      promoting women's reproductive health and rights at the service delivery level.

PMID- 19858941
TI  - "Talkin' about a revolution": How electronic health records can facilitate the
      scale-up of HIV care and treatment and catalyze primary care in resource
      constrained settings.
AB  - Health care for patients with HIV infection in developing countries has increased
      substantially in response to major international funding. Scaling up treatment
      programs requires timely data on the type, quantity, and quality of care being
      provided. Increasingly, such programs are turning to electronic health records
      (EHRs) to provide these data. We describe how a medical school in the United
      States and another in Kenya collaborated to develop and implement an EHR in a
      large HIV/AIDS care program in western Kenya. These data were used to manage
      patients, providers, and the program itself as it grew to encompass 18 sites
      serving more than 90,000 patients. Lessons learned have been applicable beyond
      HIV/AIDS to include primary care, chronic disease management, and community-based
      health screening and disease prevention programs. EHRs will be key to providing
      the highest possible quality of care for the funds developing countries can
      commit to health care. Public, private, and academic partnerships can facilitate
      the development and implementation of EHRs in resource-constrained settings.

PMID- 19858942
TI  - Strategies for more effective monitoring and evaluation systems in HIV
      programmatic scale-up in resource-limited settings: Implications for health
      systems strengthening.
AB  - Program monitoring and evaluation (M&E) has the potential to be a cornerstone of
      health systems strengthening and of evidence-informed implementation and scale-up
      of HIV-related services in resource-limited settings. We discuss common
      challenges to M&E systems used in the rapid scale-up of HIV services as well as
      innovations that may have relevance to systems used to monitor, evaluate, and
      inform health systems strengthening. These include (1) Web-based applications
      with decentralized data entry and real-time access to summary reporting; (2)
      timely feedback of information to site and district staff; (3) site-level
      integration of traditionally siloed program area indicators; (4) longitudinal
      tracking of program and site characteristics; (5) geographic information systems;
      and (6) use of routinely collected aggregate data for epidemiologic analysis and
      operations research. Although conventionally used in the context of vertical
      programs, these approaches can form a foundation on which data relevant to other
      health services and systems can be layered, including prevention services,
      primary care, maternal-child health, and chronic disease management. Guiding
      principles for sustainable national M&E systems include country-led development
      and ownership, support for national programs and policies, interoperability, and
      employment of an open-source approach to software development.

PMID- 19858943
TI  - The impact of HIV scale-up on health systems: A priority research agenda.
AB  - Although much has been learned about the implementation of HIV prevention, care,
      and treatment services in resource-limited settings, the broader impact of the
      rapid scale-up of HIV programs on fragile health systems has only recently been
      explored. A high-level working group identified priority research questions
      regarding the impact of HIV scale-up on key elements of health systems: service
      delivery; management; information, evidence, and strategic planning; medical
      products, vaccines, and technologies; health financing and payments; leadership
      and governance; and the behaviors of providers, consumers, and communities.
      Rigorous multisectoral studies are needed if HIV program expansion to the
      millions still needing care and treatment is to continue, and if the synergies
      between vertically funded HIV programs and the health systems of which they are a
      part are to be maximized to strengthen nations' ability to meet all their health
      challenges.

PMID- 19858944
TI  - Community involvement in HIV and tuberculosis research.
AB  - Since advent of the HIV pandemic in the 1980s, affected communities and
      individuals living with HIV have played key roles in leading the response to the
      crisis. Achievements of the HIV treatment activist movement include persuading
      the US Food and Drug Administration to allow expanded access to experimental
      treatments for those unable to enter controlled clinical trials; accelerated
      approval of anti-HIV drugs based on surrogate markers such as CD4 cell and HIV
      RNA changes; and the involvement of people with HIV and their advocates
      throughout the research system, including in the design, conduct, and evaluation
      of clinical trials. HIV treatment activists have adapted these skills to tackle
      tuberculosis (TB) research and programs. Considering the dearth of adequate
      diagnostic, treatment, and preventive interventions to control TB among people
      with HIV, the experiences and efforts of HIV activists are vital to accelerate
      research and development of new diagnostics, drugs, and vaccines to identify,
      cure, and prevent TB, especially among people living with HIV. Advocacy to
      implement World Health Organization collaborative HIV/TB activities and to reduce
      TB's toll among people with HIV provides a case study of how scale-up of HIV and
      TB programs contributes to health system strengthening.

PMID- 19858945
TI  - Promoting country ownership and stewardship of health programs: The global fund
      experience.
AB  - The Global Fund to Fight AIDS, Tuberculosis and Malaria was established in 2002
      to provide large-scale financing to middle- and low-income countries to intensify
      the fight against the 3 diseases. Its model has enabled strengthening of local
      health leadership to improve governance of HIV programs in 5 ways. First, the
      Global Fund has encouraged development of local capacity to generate technically
      sound proposals reflecting country needs and priorities. Second, through dual
      track financing-where countries are encouraged to nominate at least one
      government and one nongovernment principal recipient to lead program
      implementation-the Global Fund has enabled civil society and other
      nongovernmental organizations to play a critical role in the design,
      implementation, and oversight of HIV programs. Third, investments to strengthen
      community systems have enabled greater involvement of community leaders in
      effective mobilization of demand and scale-up for services to reach vulnerable
      groups. Fourth, capacity building outside the state sector has improved community
      participation in governance of public health. Finally, an emphasis on
      inclusiveness and diversity in planning, implementation, and oversight has
      broadly enhanced country coordination capacity. Strengthening local leadership
      capacity and governance are critical to building efficient and equitable health
      systems to deliver universal coverage of HIV services.

PMID- 19858946
TI  - A review of cohort study design for cardiovascular nursing research.
AB  - Nursing research encompasses a wide array of study areas that often times follow
      specific groups of patients or patient types. The cohort study design is a useful
      method to study any group, especially to track outcomes or to evaluate exposure
      or risk factors. Several different cohort study designs can be applied to the
      general population or to specific subpopulations or groups, such as those with
      cardiovascular disease. Cohort designs provide a temporal view of groups and
      exposures that can uncover outcomes and exposures that may be difficult to
      separate out in smaller, traditional experiments. There are several types of
      cohort designs, each with their unique advantages. Cohort designs may be
      prospective or retrospective. Although most cohort designs are longitudinal,
      there are also cross-sectional types of studies that are useful. As with any type
      of research design, selection of the study participants and control groups must
      be made carefully. It is important for the variables to be clearly defined and
      measurable. The investigator must also be aware of potential biases and
      weaknesses associated with different cohort study designs and account for these
      problems when they arise. Reports from cohort studies should be presented
      clearly, addressing the potential confounding problems. This article explores the
      many types of cohort designs, with examples from cardiovascular disease research
      to demonstrate how nurses can use this design in their research.

PMID- 19858947
TI  - Chinese nurses' perceptions of heart health issues facing women in China: a focus
      group study.
AB  - BACKGROUND: China is in a state of rapid economic growth and epidemiological
      transition. Morbidity and mortality relating to heart disease in women have
      increased dramatically. OBJECTIVES: The aim of this study was to obtain the views
      of nurses regarding heart health issues for women in contemporary China. DESIGN:
      : This study used focus group interviews. SETTINGS: Convenience sampling was used
      to recruit nurses working in acute care hospitals in metropolitan China. METHODS:
      Five focus groups containing 28 female participants were conducted. Focus groups
      were moderated by 2 bilingual Chinese nurses, audiotaped, and analyzed using
      thematic analysis. RESULTS: Four themes emerged from the focus group data: (1)
      mixed perceptions of disease burden in women, (2) modern life impacts upon
      women's health, (3) need for focus on prevention and coordination, and (4)
      education and support are keys to driving healthcare improvements. CONCLUSIONS:
      Heart disease, as a significant health issue for women in China, is
      underappreciated among Chinese nurses.

PMID- 19858950
TI  - "Determinants of self-care behaviors in community-dwelling patients with heart
      failure".

PMID- 19858951
TI  - Progress in prevention: the other epidemic.

PMID- 19858952
TI  - Diabetes teaching is not for the faint of heart: are cardiac nurses up to the
      challenge?
AB  - BACKGROUND: Patient education of self-care is an integral component of nursing
      care. Promoting self-care is important for patients with diabetes because day-to
      day decision making has a tremendous impact on health. PURPOSE: To examine
      diabetes knowledge of nurses working on medical cardiology and cardiovascular
      surgical intermediate care units. METHODS: In this prospective, cross-sectional,
      correlational study, 90 registered nurses working on medical cardiology and
      cardiovascular surgical units completed a 20-item survey on diabetes survival
      skill education. Correlational and comparative statistics were used to analyze
      data. RESULTS: Subjects (N = 90) were more often female (n = 73; 83.0%) and
      worked full time (n = 76; 84%); mean (SD) RN experience was 5.6 years (SD, 7.6
      years). Total mean score on the Diabetes Survival Skills Knowledge Test (DKSST)
      was 10.4 (SD, 2.6), reflecting 50% mastery of diabetes survival skill content.
      Test scores were higher in nurses with greater general comfort in teaching
      patients about diabetes (P =.04), more years of experience as a nurse (P =.004),
      more years of work at the current workplace (P <.001), and more years in their
      current work unit (P <.001). By age, nurses in the oldest quartile (> or =37
      years) had higher DKSST content area scores in oral glucose-lowering agents (P
      =.02) and symptom management (P =.01) and had a trend toward higher overall DKSST
      score (P =.06) and score on blood glucose self-monitoring (P =.06). Sex, formal
      education level, work commitment, and previous diabetes education were not
      associated with higher DKSST scores. CONCLUSION: Nurse's knowledge and comfort
      related to diabetes survival skill teaching were low. The strongest correlate of
      higher DKSST score was length of time as a nurse. Because previous education and
      other nurse characteristics were not associated with higher test scores, nurse
      educators and advanced practice nurses must modify education delivery modalities
      to improve retention of information used in the delivery of patient education
      about diabetes survival skills.

PMID- 19858953
TI  - Impact of a nurse telephone intervention among high-cardiovascular-risk, health
      fair participants.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of
      death in the United States, yet most individuals remain unaware of their risk.
      Current health fair models assess individual risk factors but miss the
      opportunity to assess, counsel, and follow-up with participants regarding global
      CVD risk. Objectives of this nurse telephone intervention were to (1) describe
      high-CVD-risk participants' healthcare-seeking behavior after the health fair and
      following a nurse telephone intervention and (2) describe CVD risk-reducing
      therapies provided to high-risk participants after the health fair and following
      a nurse telephone intervention. SUBJECTS AND METHODS: Five hundred twenty-nine of
      4,489 health fair participants who completed an interactive Framingham risk
      assessment in 2006 were identified with high CVD risk. These participants
      received a nurse telephone intervention approximately 1 month after the health
      fair, during which the risk message was reinforced, principles of motivational
      interviewing were applied, and follow-up care was assessed. We evaluated the
      proportion of high-CVD-risk participants who obtained healthcare before and after
      intervention, and we compared the care received before and after intervention.
      RESULTS AND CONCLUSION: Among 447 contacted high-CVD-risk participants, 59% (n =
      262) saw a healthcare provider, and 86% of those discussed CVD risk at their
      healthcare visit. A greater proportion of participants were started on a
      cardioprotective drug (41% vs 20%; P < .01), and more participants discussed
      "heart health" (96% vs 75%; P < .001) after receiving the nurse telephone
      intervention. Our findings suggest that a nurse intervention may improve
      individuals' CVD risk awareness as well as activate providers to implement CVD
      risk reduction strategies.

PMID- 19858954
TI  - Expectations, anxiety, depression, and physical health status as predictors of
      recovery in open-heart surgery patients.
AB  - BACKGROUND AND OBJECTIVES: Recovery after open-heart surgery is a complex process
      that presents psychosocial and physical challenges that continue well after
      discharge. The purpose of this study was to examine the relationship among
      expectations, anxiety, depression, and physical health status (PHS) and to
      determine predictors of postoperative PHS in open-heart surgery patients.
      PARTICIPANTS AND METHODS: A convenience sample (N = 54) was recruited from 2
      hospitals in rural regions from 2 different mid-Atlantic states. The sample
      included participants who underwent coronary artery bypass graft or valve
      replacement surgery for the first time. The study used a longitudinal design, and
      data were collected preoperatively in the hospital or surgeons' offices and 4
      weeks postoperatively by telephone interviews. Participants were interviewed
      using the following questionnaires: the Future Expectations Regarding Life with
      Heart Disease scale, the Hospital Anxiety and Depression scale, and the Medical
      Outcomes Study 36-Item Short Form Health Survey. Repeated-measures analysis of
      variance, Pearson product-moment correlations, and multiple regression were used
      for data analyses. RESULTS AND CONCLUSIONS: Statistical analysis revealed that
      anxiety (P = .002) and depression (P = .026) scores decreased postoperatively.
      Significant relationships were found among the preoperative and postoperative
      variables: expectations, anxiety, depression, and PHS. Analyses also found that
      preoperative expectations, anxiety, depression, and PHS contributed 38% of the
      variance of postoperative PHS (P < .001). However, the postoperative variables
      were not significant predictors of postoperative PHS (P = .075). The findings
      support the need for interventions to assist patients in developing realistic
      expectations and for clinicians to screen patients for anxiety and depression
      before and after surgery. Future research needs to measure PHS at various times
      postoperatively to identify continued limitations after surgery.

PMID- 19858955
TI  - Factors associated with long hospital length of stay in patients receiving
      warfarin after cardiac surgery.
AB  - BACKGROUND: Patients receiving warfarin therapy after coronary artery bypass
      graft (CABG) or valve surgery have longer length of stay (LOS) than those not
      receiving warfarin therapy. Longer LOS increases patient costs, postdischarge
      recovery time, and rehabilitation. It is important to identify variables of
      longer postoperative LOS in this patient population so that the healthcare team
      can develop and facilitate interventions to minimize length of hospitalization.
      METHODS: Using a hospital registry and medical record review of cases completed
      in 2004, data from cardiac surgery patients having CABG and/or valve procedures
      and given warfarin postoperatively were analyzed based on short (<7 days, CABG; 9
      days, valve procedure) and long (> or =7 days, CABG; > or =9 days, valve
      procedure) postoperative LOS. By groups, significant associations were assessed
      using chi or Fisher exact test for categorical variables and Wilcoxon 2-sample
      test or Student t test for continuous variables. RESULTS: In 82 patients (33 CABG
      and 49 valve +/- CABG) who were given warfarin, most demographic, medical
      history, postoperative complications, and use of cardiac drugs did not predict
      longer LOS. Longer postoperative LOS was associated with being older (mean age,
      73.5 vs 68.5 years), being not married, having postoperative respiratory
      insufficiency, and receiving more red blood cell transfusions, all P < .05; and
      having more healthcare consultations, longer critical care stay, and longer time
      between surgery date and start of warfarin; all P < .001. CONCLUSIONS: Variables
      associated with longer LOS were nonmodifiable by nursing services and were
      difficult to assess preoperatively. They primarily involved intraoperative or
      postoperative bleeding that led to red blood cell infusion and longer critical
      care stays that delayed warfarin initiation. However, older age and marital
      status are nursing targets because they may be associated with social isolation
      and other psychosocial issues. Transition of care programs can be developed to
      promote earlier discharge.

PMID- 19858956
TI  - Predictors of dropout from a multidisciplinary heart failure program: a nested
      case study.
AB  - BACKGROUND: Chronic heart failure is a growing public health issue that is
      reaching epidemic proportions. In the last few years, multidisciplinary
      management programs have been developed to improve its management. Yet, some
      patients take advantage of these programs, whereas others do not. METHODS:
      Several demographic, medical, and social variables were evaluated as contributors
      to dropout after enrollment into a multidisciplinary heart failure program using
      a nested case-control design. A total of 14 patients and 42 controls were
      interviewed using a standardized questionnaire. Possible associations were
      explored by means of chi Mantel-Haenszel test and a binary logistic regression
      model. RESULTS: The only significant factor associated with dropout was social
      isolation. Patients who lived alone, without family support, had a significantly
      greater dropout risk (odds ratio, 12.5; 95% confidence interval, 1.35-11.6).
      CONCLUSIONS: For patients who live alone, an individualized approach may be
      better than a multidisciplinary management program, but this hypothesis should be
      investigated in future studies.

PMID- 19858957
TI  - Commentary on the study "predictors of dropout from a multidisciplinary heart
      failure program: a nested case study".

PMID- 19858958
TI  - Commentary: developing knowledge and improving care using the self-care of heart
      failure index.

PMID- 19858960
TI  - Venous thromboembolism: commentary on prevention and treatment.

PMID- 19858959
TI  - Development, psychometric testing, and revision of the Atlanta Heart Failure
      Knowledge Test.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Several heart failure (HF) knowledge tools
      have been developed and tested over the past decade; however, they vary in
      content, format, psychometric properties, and availability. This article details
      the development, psychometric testing, and revision of the Atlanta Heart Failure
      Knowledge Test (A-HFKT) as a standardized instrument for both the research and
      clinical settings. PARTICIPANTS AND METHODS: Development and psychometric testing
      of the A-HFKT were undertaken with 116 New York Heart Association (NYHA) class II
      and III community-dwelling HF patients and their family members (FMs)
      participating in a family intervention study. Internal consistency, reliability,
      and content validity were examined. Construct validity was assessed by
      correlating education level, literacy, dietary sodium ingestion, medication
      adherence, and healthcare utilization with knowledge. RESULTS: Content validity
      ratings on relevance and clarity ranged from 0.55 to 1.0, with 81% of the items
      rated from 0.88 to 1.0. Cronbach alpha values were .84 for patients, .75 for FMs,
      and .73 for combined results. Construct validity testing revealed a small but
      significant correlation between higher patient and FM knowledge on sodium
      restriction questions and lower ingested sodium, r = -0.17, P = .05 and r = 
      0.19, P = .04, respectively, and between patient knowledge and number of days
      that medications were taken correctly (diuretics: r = 0.173, P < .05, and
      angiotensin-converting enzyme: r = 0.223, P = .01). Finally, patients seeking
      emergency care or requiring hospitalization in the 4 months before study entry
      were found to have significantly lower FM knowledge using both t test and
      logistic regression modeling. CONCLUSIONS: The A-HFKT was revised using the
      content and construct validity data and is available for use with HF patients and
      FMs. The construct validity testing indicates that patient knowledge has a
      significant relationship to aspects of self-care. Furthermore, family knowledge
      may influence patient adherence with sodium restriction and healthcare
      utilization behavior.

PMID- 19858961
TI  - Venous thromboembolism: what is preventing achievement of performance measures
      and consensus guidelines?
AB  - Venous thromboembolism (VTE) is a major cause of death and disability throughout
      the world. Evidenced-based guidelines and performance measures aimed at
      prevention of VTE have existed for over a decade, yet VTE occurrence rate appears
      to be increasing. This increase may, in part, be due to more aggressive
      surveillance; however, noncompliance with guideline recommendations for
      prophylaxis is a concern. Several barriers have been identified as contributing
      to lack of guideline adherence including lack of supportive systems, lack of
      individual responsibility for implementation, lack of acceptance, perceived lack
      of need in some clinical areas, no oversight or incentives, and conflicting
      guideline recommendations. Distribution of guidelines to healthcare providers
      does not result in increased guideline adherence. Applying multiple process
      improvement strategies appears to increase guideline utilization and may help
      achieve improved patient outcomes and higher performance measures.

PMID- 19858962
TI  - Venous thromboembolism: a chronic illness.
AB  - Deep vein thrombosis (DVT) is a common disorder frequently seen in both the
      inpatient and outpatient settings. DVT increases the risk of pulmonary embolism,
      a potentially fatal complication. These 2 conditions--DVT and pulmonary embolism-
      comprise venous thromboembolism (VTE), which is a major and often unrecognized
      cause of morbidity and mortality in hospitalized and ambulatory patients.
      Acquired risk factors include smoking, obesity, stasis (such as long-term
      travel), hypercoagulability, recent surgery, trauma, or hospitalizations. In
      addition, inherited or innate disorders that pose risk include increasing age and
      personal or family history of VTE.After a first episode of VTE, the risk for
      recurrent episodes of a DVT is elevated: 21.5% after a first event and 27.9%
      after a second. And, the risk of recurrence varies with time, with highest risk
      occurring during the first 6 to 12 months after the event. Death occurs in 6% of
      DVT cases within 1 month of diagnosis. Once a DVT occurs, the risk recurrence
      never resolves to zero; therefore, VTE should be considered a chronic illness
      rather than a short-term condition. As a key member of the healthcare team, the
      role a nurse practitioner is to identify patients at risk for VTE and institute
      appropriate preventative/treatment measures. By doing so, morbidity and mortality
      from this common disorder can be minimized.

PMID- 19858963
TI  - Venous thromboembolism: pharmacological and nonpharmacological interventions.
AB  - The formation of blood clots is a significant threat to individuals with limited
      mobility, whether in the hospital or recovering in an outpatient setting.
      Prevention of deep vein thrombosis and pulmonary embolism has been found to be
      cost-effective when compared with treating an existing thrombosis. Despite these
      positive findings, compliance with the clinical practice guidelines is less than
      ideal. The National Consensus Standards for the Prevention and Care of Deep Vein
      Thrombosis Project identified 4 domains to address the problem of noncompliance
      related to venous thromboembolism: risk assessment, diagnosis, prevention, and
      treatment.The objective of treating an existing deep vein thrombosis is to
      prevent further extension of the clot. Pharmacological interventions for both
      prevention and treatment include unfractionated heparin, low-molecular-weight
      heparin, selective factor Xa inhibitors, and vitamin K antagonists;
      nonpharmacological interventions include mechanical measures, such as inferior
      vena cava filters, graduated compression stockings, and intermittent pneumatic
      compression devices. Pharmacological interventions interfere with various factors
      of the coagulation cascade. An adverse effect commonly associated with these
      drugs is excessive bleeding. The mechanism of action surrounding mechanical
      interventions is to increase venous return and decrease the risk of pooling of
      blood in the leg veins. These interventions are effective only if implemented.
      Clinical application of clinical practice guidelines is imperative to protect
      patients at risk.

PMID- 19858964
TI  - Educational, vocational, psychosocial, and quality-of-life outcomes for adult
      survivors of childhood traumatic brain injury.
AB  - OBJECTIVE: To examine long-term outcomes from child traumatic brain injury (TBI)
      and relevance of injury severity. DESIGN: A retrospective cross-sectional design.
      PARTICIPANTS: One hundred and twenty-four young adult survivors of childhood TBI
      (81 men), aged 18 to 30 years at evaluation (mean = 23.5, SD = 2.9), with injury
      on average 13.7 years prior to evaluation divided according to injury severity:
      mild (n = 60), moderate (n = 27), and severe (n = 37). MAIN MEASURES:
      Questionnaires assessed educational and employment status, psychosocial function,
      and quality-of-life issues. RESULTS: Functional difficulties persisted into
      adulthood. Injury severity was a particularly strong predictor of long-term
      outcomes, with environmental factors playing a less consistent role. Survivors of
      severe TBI were particularly vulnerable, demonstrating global impairment: poorer
      school performance, employment difficulties, poor quality of life, and increased
      risk of mental health problems. Mild and moderate TBI were more benign, although
      lower educational attainment and employment status were identified, and moderate
      TBI was associated with late developing mental health issues. CONCLUSIONS:
      Traumatic brain injury is a lifelong problem, compromising the individual's
      capacity to meet developmental expectations across a wide range of functional
      domains.

PMID- 19858965
TI  - Training emotional processing in persons with brain injury.
AB  - AIMS: To determine the effectiveness of 2 interventions for different aspects of
      emotion-processing deficits in adults with acquired brain injury (ABI).
      PARTICIPANTS: Nineteen participants with ABI (minimum 1 year postinjury) from
      Western New York and Southern Ontario, Canada. INTERVENTIONS: (1) Emotion
      processing from faces ("facial affect recognition" or FAR) and (2) emotion
      processing from written context by using "stories of emotional inference" (SEI).
      Ten randomly assigned participants received the FAR intervention, and 9 received
      the SEI protocol. Both interventions were administered 1 hour per day, 3 times
      per week, and completed in 6 to 9 sessions, and both incorporated participants'
      personal emotional experiences into training. OUTCOME MEASURES: (1) Facial
      affect, (2) vocal affect, (3) affect from videos, (4) emotional inference from
      context, and (5) emotional behavior. There were 2 pretests, a posttest, and a 2
      week follow-up. RESULTS: FAR participants showed significantly improved emotion
      recognition from faces, ability to infer emotions from context, and
      socioemotional behavior, while the SEI group members exhibited significantly
      improved ability to infer how they would feel in a given context. CONCLUSION:
      Training can improve emotion perception in persons with ABI. Although further
      research is needed, the interventions are clinically practical and show promise
      for the population with ABI.

PMID- 19858966
TI  - Psychiatric disorders following traumatic brain injury: their nature and
      frequency.
AB  - OBJECTIVES: To retrospectively establish the nature and frequency of Axis I
      psychiatric disorders pre- and post-TBI. PARTICIPANTS: One hundred participants
      who were 0.5 to 5.5 years post mild to severe TBI and 87 informants, each
      evaluated at a single time point. MAIN MEASURE: The Structured Clinical Interview
      for DSM-IV Disorders (SCID-I). RESULTS: Preinjury, 52% received a psychiatric
      diagnosis, most commonly substance use disorder (41%), followed by major
      depressive disorder (17%) and anxiety (13%). Postinjury, 65% received a
      diagnosis, of which major depression became the most common (45%), followed by
      anxiety (38%) and substance use disorder (21%). Frequency of depression,
      generalized anxiety disorder, posttraumatic stress disorder, panic disorder, and
      phobias rose from preinjury to postinjury. More than two-thirds of postinjury
      depression and anxiety cases were novel and showed poor resolution rates. Few
      novel cases of substance use disorder were noted. Psychotic disorders, somatoform
      disorders, and eating disorders occurred at frequencies similar to those in the
      general population. CONCLUSIONS: A high frequency of postinjury psychiatric
      disorders was evident up to 5.5 years postinjury, with many novel cases of
      depression and anxiety. Individuals with TBI should be screened for psychiatric
      disorders at various time points post-injury without reliance on history of
      psychiatric problems to predict who is at risk, so that appropriate intervention
      can be offered.

PMID- 19858967
TI  - Emergency department assessment of mild traumatic brain injury and the prediction
      of postconcussive symptoms: a 3-month prospective study.
AB  - OBJECTIVE: To investigate the utility of a brief emergency department (ED)
      bedside screen for the prediction of postconcussive symptoms at 3 months
      following mild traumatic brain injury (MTBI). PARTICIPANTS: One hundred patients
      with MTBI (78% men; mean age = 33.6 years); 2 control groups (each n = 100), a
      "minor nonhead injury" group (77% men; mean age = 32.2 years) and an "uninjured
      ED visitor" group (78% men; mean age = 33.6 years). MAIN MEASURES: Brief measures
      of neuropsychological functioning, acute pain, and postural stability were
      collected in the ED; telephone follow-up at 3 months using the Rivermead Post
      Concussion Symptoms Questionnaire was undertaken. RESULTS: Neuropsychological
      deficits, acute pain, and postural instability in the ED were significantly
      associated with postconcussive symptoms at 3-month follow-up. A regression
      formula using 3 easily obtainable measures obtained during acute stage of injury
      immediate and delayed memory for 5 words and a visual analog scale score of acute
      headache-provided 80% sensitivity and 76% specificity for the prediction of
      clinically significant symptoms at 3 months postinjury. CONCLUSION: A small
      combination of variables assessable in the ED may predict MTBI patients likely to
      experience persistent postconcussive symptoms.

PMID- 19858968
TI  - Preinjury factors and 3-month outcomes following emergency department diagnosis
      of mild traumatic brain injury.
AB  - OBJECTIVE: To investigate the sequelae of mild traumatic brain injury (MTBI) by
      comparing selected outcomes of emergency department-diagnosed patients with mild
      head injuries to those with non-head injuries. SETTING: Five emergency
      departments in southern California. PARTICIPANTS: Two cohorts, one with MTBI (n =
      689 at initial assessment) and another with non-head injuries (n = 1318). MAIN
      MEASURES: Rivermead Post-Concussion Symptoms Questionnaire and Pittsburgh Sleep
      Quality Index at 3 months postinjury. RESULTS: Postconcussion symptom rates and
      summary Rivermead Post-Concussion Symptoms Questionnaire scores were
      significantly higher for persons with MTBI than for the comparison cohort. Women
      reported significantly more symptoms than men. Complaints about sleep quality
      overall (and also sleep latency and daytime dysfunction subcomponents) were
      significantly more frequent among those with MTBI. CONCLUSION: Patients with MTBI
      have significantly more negative outcomes than patients in the comparison cohort
      and should be clinically managed with these prevalent outcomes in mind. Further
      study of follow-up medical management and the development of treatment guidelines
      for this group of patients are both warranted.

PMID- 19858969
TI  - Using activity diaries to measure children's and adolescents' compliance with
      activity restrictions after mild traumatic brain injury.
AB  - PURPOSE: To examine the extent to which children and adolescents with a mild
      traumatic brain injury (MTBI) comply with the activity restrictions received upon
      discharge from a pediatric trauma center. PARTICIPANTS: Thirty-four children with
      MTBI (aged 8-16 years) and 34 control children matched for age, sex, and
      premorbid level of physical activity. MAIN MEASURE: Activity diary documenting
      the exact level of activity during 3 consecutive days during the 1st, 4th, and
      12th week post-MTBI (corresponding time intervals for controls) and the Physical
      Activity Questionnaire. RESULTS: Fifteen pairs of children (MTBI + control)
      completed the diaries for all 3 assessment times (77% participation rate among
      consecutive admissions and 44% compliance rate with diary completion). Although
      some children engaged in activities before the end of the 4-week restriction
      period, the majority of the children followed the recommendations they received.
      Children with MTBI maintained a lower level of energy expenditure at the 1- and 4
      week evaluations than did the noninjured children, but not at the 12-week
      evaluation. CONCLUSION: Children with MTBI usually comply with the activity
      restrictions they receive upon discharge from the hospital.

PMID- 19858970
TI  - Static and dynamic visuomotor task performance in children with acquired brain
      injury: predictive control deficits under increased temporal pressure.
AB  - OBJECTIVE: To compare performance of children with acquired brain injury (ABI) on
      static versus dynamic visuomotor tasks with that of control children.
      PARTICIPANTS: Twenty-eight children with ABI and 28 normal age- and gender
      matched controls (aged 6-16 years). MAIN MEASURES: Two visuomotor tasks on a
      digitizing tablet: (1) a static motor task requiring tracing of a flower figure
      and (2) a dynamic task consisting of tracking an accelerating dot presented on a
      monitor. RESULTS: Children with ABI performed worse than the control group only
      during the dynamic tracking task; the duration within the target was shorter, the
      distance between the centers of cursor and target was larger, and the number of
      velocity peaks per centimeter and the number of stops (ie, the number of
      submovements) were higher than those of the control group. Rather than resulting
      from movement execution problems, this might be due to less adequate processing
      of fast incoming sensory information, resulting in a decreased ability to
      anticipate the movement of the target (predictive control). CONCLUSION: Deficits
      in eye-hand coordination require careful attention, even in the postinjury
      chronic phase.

PMID- 19858971
TI  - Laryngeal function: a comparative analysis between children and adults subsequent
      to traumatic brain injury.
AB  - OBJECTIVE: To evaluate laryngeal function and speech disorders in children and
      adults with traumatic brain injury (TBI) by applying both perceptual and
      instrumental analysis. PARTICIPANTS: 15 children and 15 adults with moderate to
      severe acquired TBI and 2 control groups (19 adults and 16 children). MAIN
      MEASURES: A battery of perceptual analyses (the Frenchay Dysarthria Assessment
      (FDA) and speech sample assessment) and instrumental techniques
      (electrolaryngographic and computerized airflow/air pressure analysis systems
      Aerophone II). RESULTS: While children with TBI exhibited fewer speech disorders
      (based on the deviant laryngeal features) than did the adult group with TBI
      during the perceptual assessments, the significant differences found between both
      groups using electroglottography (EGG) analysis for the laryngeal function
      investigation could be explained by the anatomical and physiological differences
      between adults and children. Consistent with the findings based on
      electroglottography, the aerodynamic analysis carried out in the present study
      failed to demonstrate significant changes in laryngeal function following TBI in
      either adults or children. CONCLUSIONS: Four reasons may explain the differences
      between children and adults: (1) the different types of injury can vary the
      degree of neurologic impairment, (2) potential differences during recovery, (3)
      the developmental changes in, or level of maturation of, laryngeal function in
      the pediatric group and, (4) time postinjury. Because of these variations,
      children may be better able to compensate for any impairment.

PMID- 19858972
TI  - Feasibility of instrumental swallowing assessments in patients with prolonged
      disordered consciousness while undergoing inpatient rehabilitation.
AB  - OBJECTIVE: To evaluate the feasibility, safety, and potential benefit of
      instrumental swallowing assessments for patients with prolonged disordered
      consciousness participating in rehabilitation. DESIGN: Case-control,
      retrospective. PARTICIPANTS: Thirty-five participants divided into 2 cohorts
      according to cognitive level at the time of baseline instrumental swallowing
      assessment. Group 1 (n = 17) participants were at Rancho Los Amigo (RLA) level
      II/III or RLA level III, while Group 2 (n = 18) participants were rated better
      than RLA level III. RESULTS: Aspiration and laryngeal penetration rates for both
      groups were similar (aspiration rate Group 1 = 41%, Group 2 = 39%; laryngeal
      penetration rate Group 1 = 59%, Group 2 = 61%). Overall, 76% (13/17) of Group 1
      and 72% (13/18) of Group 2 were able to receive some type of oral feedings
      following baseline video fluoroscopic swallow study (VFSS) or endoscopic exam of
      the swallow (FEES). CONCLUSION: The majority of participants who underwent an
      instrumental swallowing examination while still functioning at RLA level II/III
      or RLA level III were able to return to some form of oral feedings immediately
      following their baseline examination. Swallowing as a treatment modality can be
      considered a part of the overall plan to facilitate neurobehavioral recovery for
      patients with prolonged disordered consciousness participating in rehabilitation.

PMID- 19858973
TI  - Best practice guidelines for forensic neuropsychological examinations of patients
      with traumatic brain injury.

PMID- 19858976
TI  - Canine investigation of rhBMP-2, autogenous bone graft, and rhBMP-2 with
      autogenous bone graft for the healing of a large segmental tibial defect.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of bone
      morphogenetic protein, bone morphogenetic protein with autogenous bone graft
      (ABG), and ABG alone on the healing of a large bone defect in the canine tibia.
      METHODS: Fifteen 45- to 55-lb canines were randomly assigned to 1 of 5 treatment
      groups, 3 per group. The groups included (1) recombinant human bone morphogenetic
      protein (rhBMP-2, 0.43 mg/mL)/absorbable collagen sponge (ACS) + collagen/ceramic
      matrix (CCM), (2) rhBMP-2 (0.22 mg/mL) ACS + CCM, (3) rhBMP-2 (0.43 mg/mL) ACS +
      ABG, (4) rhBMP-2 (0.22 mg/mL) ACS + ABG, and (5) ABG alone. A 5-mL defect was
      created in the right tibia and fixed with a 4.5 mm locking plate and 1 of the
      grafts described above implanted. X-rays were taken biweekly for 12 weeks and
      evaluated for radiographic union. Representative histology was also examined.
      RESULTS: All defects treated with rhBMP-2 (any combination) healed at 6.0 +/- 0.9
      weeks. None of the ABG alone-treated defects were healed at 12 weeks. Dogs
      receiving rhBMP-2/ACS + CCM healed at 5.7 +/- 0.8 weeks, whereas rhBMP-2/ACS +
      ABG defects healed at 6.3 +/- 0.8 weeks. Histology showed healing consistent with
      12-week radiologic results. CONCLUSIONS: Large segmental defects in canine tibiae
      can be effectively healed with stable fixation and rhBMP-2/ACS + ABG or CCM.
      These conclusions may offer insight into the clinical treatment of segmental
      defect nonunions in the human.

PMID- 19858977
TI  - Ability of recombinant human bone morphogenetic protein 2 to enhance bone healing
      in the presence of tobramycin: evaluation in a rat segmental defect model.
AB  - OBJECTIVE: To determine whether locally applied tobramycin influences the ability
      of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental
      defect in the rat femur. METHODS: The influence of tobramycin on the osteogenic
      differentiation of mesenchymal stem cells was first evaluated in vitro. For the
      subsequent, in vivo experiments, a 5-mm segmental defect was created in the right
      femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator
      and four Kirschner wires. Rats were divided in four groups: empty control,
      tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 microg)/absorbable
      collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone
      healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at
      8 weeks and the properties of the defect were compared with the intact
      contralateral femur. Bone formation in the defect region was assessed by dual
      energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical
      testing. RESULTS: Tobramycin exerted a dose-dependent inhibition of alkaline
      phosphatase induction and calcium deposition by mesenchymal stem cells cultured
      under osteogenic conditions. The inhibition was reversed in the presence of 500
      ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the
      absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of
      rhBMP-2 to heal these defects and increased the bone area of the defects treated
      with rhBMP-2. Data obtained from all other parameters of healing, including dual
      energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical
      testing, were unaffected by tobramycin. CONCLUSIONS: Although our in vitro
      results suggested that tobramycin inhibits the osteogenic differentiation of
      mesenchymal stem cells, this could be overcome by rhBMP-2. Tobramycin did not
      impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats.
      Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with
      tobramycin. This study shows that locally applied tobramycin can be used in
      conjunction with rhBMP-2 to enhance bone formation at fracture sites.

PMID- 19858978
TI  - A single-channel telemetric intramedullary nail for in vivo measurement of
      fracture healing.
AB  - OBJECTIVE: The objective of this study was to develop a single-channel telemetric
      intramedullary nail that measures anterior-posterior bending strains and
      determine whether these forces decrease sigmoidally when normalized to the ground
      reaction force during fracture healing. METHODS: A transverse midshaft femoral
      osteotomy (1 mm) was stabilized using a customized TriGen intramedullary nail
      incorporating a strain gauge in the anterior-posterior plane. Fourteen skeletally
      mature sheep (2-3 years old) were treated in two pilot studies (n = 3/pilot) and
      a pivotal study (n = 8). Three animals were excluded as a result of welfare
      issues. Static strain measurements were acquired at approximately 130 Hz during
      leg stance. In vivo gait analysis was carried out weekly to assess ground
      reaction forces and biweekly x-rays to assess stability and fracture healing.
      Animals were euthanized 12 weeks postoperatively. Callus formation was assessed
      by microcomputed tomography and histomorphometry. The degree of load share
      between bone and the nail was determined postmortem by three-point bending.
      RESULTS: A significant preload was generated during implantation, most notably
      during placement of the four interlocking screws and by the action of attached
      soft tissues. Eight animals showed evidence of bone healing by x-ray,
      microcomputed tomography, and histology. However, a reduction in implant load was
      only observed with two of the eight. The degree of load sharing observed in vivo
      in these animals (50%-75%) compared favorably with the in vitro observations
      (approximately 50%). In the nonhealing ambulating animals, nail forces did not
      change over time. Three-point bend tests carried out on "healed" femurs suggested
      that load sharing between the bone and nail could be detected more easily in the
      absence of soft tissues. CONCLUSION: No clear correlation between implant strain
      and fracture healing was observed using the single-channel system when subjected
      to one external loading regime (leg stance phase). However, ex vivo biomechanical
      testing demonstrated that load share changes could be detected when loads were
      directly applied to the bone in the absence of muscle and ligament forces. These
      data emphasize the need to fully characterize the complex biomechanical
      environment of the limb to determine the load changes resulting from fracture
      healing.

PMID- 19858979
TI  - Intraoperative waste of trauma implants: a cost burden to hospitals worth
      addressing?
AB  - OBJECTIVES: The purposes of this study were to assess the incidence of
      intraoperative trauma implant waste in a regional territory of the United States
      and to assess its impact on costs. METHODS: The total number of procedures using
      a single device manufacturer's orthopaedic trauma implants in one geographic
      region and number of occurrences of intraoperative orthopaedic trauma implant
      waste were recorded prospectively from 74 contiguous hospitals over a period of
      18 months along with the individual responsible for the waste (surgeon, vendor
      representative, or operating room staff), the cost of the wasted implant, and
      whether the hospital paid for the implant. Hospitals were stratified into
      teaching or community institutions. The collected data were then aggregated and
      analyzed for overall incidence and cost as well as cost per trauma procedure.
      RESULTS: Implant waste occurred in 37 of 6531 procedures (0.6%) with 16 of the
      centers (21.6%) reporting at least one occurrence and 95% attributed to the
      surgeon or operating room staff. Community hospitals were found to have a
      significantly higher incidence of implant waste as compared with teaching
      hospitals. Hospitals absorbed 74% of the wasted implant costs ($20,357 over the
      study period). This expense represented a mean additional cost of $3.12 per
      orthopaedic trauma procedure performed. CONCLUSIONS: There is a small but notable
      annual incidence and cost of orthopaedic trauma implant waste in the study region
      with the majority of this cost borne by the hospitals. However, implant waste
      occurs infrequently and represents a very small cost to hospitals per procedure.
      Educational programs and other strategies to reduce its incidence are unlikely to
      yield any substantial cost savings.

PMID- 19858980
TI  - Surgeons and their patients disagree regarding cosmetic and overall outcomes
      after surgery for high-energy lower extremity trauma.
AB  - OBJECTIVES: To determine whether surgeons' and patients' perceptions of outcomes
      after high-energy lower-extremity trauma are similar and to identify factors
      associated with disagreement. DESIGN: Prospective study. SETTING: Eight level 1
      trauma centers. PATIENTS: Four hundred sixty-three patients treated for limb
      threatening lower extremity injuries and followed for 2 years. INTERVENTION:
      Information collected on patients and injuries, functional and clinical outcomes,
      and surgeons' and patients' assessments of satisfaction with cosmetic and overall
      recovery. MAIN OUTCOME MEASUREMENTS: Satisfaction ratings compared with weighted
      kappa statistics. RESULTS: We observed very poor agreement between surgeons' and
      patients' perceptions of cosmetic and overall outcomes. Surgeons and patients
      agreed on overall outcomes at a rate only 25% higher than expected by chance
      (kappa = 0.25; 95% confidence interval, 0.05-0.34). The level of disagreement was
      even higher for cosmetic outcomes as surgeons and patients agreed at a rate only
      17% higher than expected by chance (kappa = 0.17; 95% confidence interval, 0.09
      0.26). Surgeons were less likely than patients to be satisfied with overall
      recovery if the patient had an Injury Severity Score >17, had a complication, or
      failed to return to work at 1 year. Patients were less satisfied than surgeons
      with overall recovery when the patient was dissatisfied with the quality of
      medical care. Surgeons were less likely than patients to be satisfied with
      cosmetic recovery if the patient sustained a traumatic amputation or experienced
      a complication. Patients were less likely than surgeons to be satisfied with
      cosmetic recovery if the patient was female or was dissatisfied with his or her
      medical care. CONCLUSIONS: Surgeons' perceptions of patients' cosmetic and
      overall outcomes differed significantly from those of patients. Agreement was
      significantly worse for certain subgroups of patients. Further study of this
      discordance might improve our understanding of patient dissatisfaction and allow
      development of a more patient-centered care process.

PMID- 19858981
TI  - Pin site care during circular external fixation using two different protocols.
AB  - OBJECTIVES: Treatment of tibial fractures with Ilizarov external fixation is a
      valuable treatment alternative; however, development of problems at the pin site
      is one of the major drawbacks of this technique. Moreover, there is no general
      agreement regarding pin site care. The purpose of this study was to compare the
      efficacy of two different pin site care techniques after treatment of tibial
      fractures with an Ilizarov external fixator. DESIGN: Prospective randomized
      study. SETTING: Department of Orthopaedic Surgery of education and research
      hospital. PATIENTS AND METHODS: In this prospective randomized study, we followed
      up 610 pin sites in 39 cases using two different pin site care protocols.
      INTERVENTION: For the first 15 days, patients in both groups cleaned each pin
      site using sterile gauze impregnated with 10% polyvinylpyrrolidone iodine
      (Polyod) every 3 days. After 15 days, patients in group 1 (20 cases, 310 pin
      sites) were advised to perform pin care by daily showering and brushing the pin
      sites with soap and an ordinary soft toothbrush, whereas patients in group 2 (19
      cases, 300 pin sites) were advised to perform pin care by daily showering and
      cleaning the crusts using sterile gauze impregnated with 10% polyvinylpyrrolidone
      iodine (Polyod). Each pin site was denominated according to location. MAIN
      OUTCOME MEASUREMENTS: Pin sites were inspected and graded on a scale of 0 to 5
      according to slight modification of the system of Dahl described by Gordon et al
      during outpatient visits on the 5th, 10th, 15th, 30th, 45th, 60th, 75th, 90th,
      120th, and 150th days of follow up after the operation until fixator removal.
      Grade 1 and grade 2 infections were categorized as minor infection not requiring
      any extra pin site care and grade 3 and above infections as major infection.
      RESULTS: Minor infection rate of all pin sites was determined as 50.7% in group 1
      and 43.6% in group 2. Major infection rate was determined as 3.5% in group 1 and
      3.7% in group 2. No statistically significant difference was noted between the
      two groups (all P > 0.05). CONCLUSION: Pin site care can be performed without
      impairing patient comfort and without prohibition of showering. Pin site care can
      be self-managed by the patients without complex sterilization techniques.

PMID- 19858982
TI  - The bicipital aponeurosis may be involved in the anatomical etiology of arterial
      compromise after swelling in supracondylar fracture.
AB  - A 7-year-old girl presented with a Gartland grade III supracondylar fracture and
      no radial pulse. After open reduction, it was established that the brachial
      artery was free of the fracture site; the limb however remained nonviable. The
      brachial artery was then approached anteriorly and the bicipital aponeurosis was
      seen to kink the artery. Once the bicipital aponeurosis was released and the
      remaining spasm treated with arteriotomy and papaverine, a good pulse returned.
      Despite the fracture being reduced and the artery remaining free of it, there
      remained a structural impediment to flow in the brachial artery. If the pulse
      does not return after fixation of a supracondylar fracture, then exploration of
      the brachial artery is indicated. When a patient is taken to the operating room
      for fixation of a supracondylar fracture, the facilities and expertise to explore
      the brachial artery must be made available. In centers where an on-call vascular
      service is not available, we recommend that the orthopaedic training programs
      give consideration to including "exploration of the brachial artery" as a facet
      of orthopaedic surgical training.

PMID- 19858983
TI  - Completely displaced S-1/S-2 growth plate fracture in an adolescent: case report
      and review of literature.
AB  - In children, pelvic fractures are not common, and therefore, sacral fractures are
      a rare occurrence. Sacral fractures are often associated with neurologic deficit.
      Using radiographs alone may not be adequate to diagnose sacral fractures, and
      computed tomography scanning and/or magnetic resonance imaging may be needed.
      Treatment of the sacral fracture is often controversial and can range from
      nonoperative management to surgical intervention. This article presents a case
      report of completely displaced S-1/S-2 growth plate fracture. It also describes
      our diagnostic and treatment approach based on similar previously reported cases.

PMID- 19858984
TI  - Distal radius fractures.
AB  - Distal radius fractures are a common injury, particularly in the elderly
      population. Severity of these fractures is directly related to the bone mineral
      density of the patient, and clinical results are dependent on this parameter as
      well. In terms of treatment, several options exist. Nonoperative management
      consists of closed treatment with casting. Operative treatment options include
      intrafocal pinning, nonbridging and bridging external fixation, arthroscopic
      assisted external fixation, and various methods of open reduction internal
      fixation. When operative intervention is indicated, considerations include the
      characteristics of the fracture and the experience of the surgeon with the
      treatment modalities.

PMID- 19858985
TI  - A modified anterior exposure to the acetabulum for treatment of difficult
      anterior acetabular fractures.

PMID- 19858991
TI  - Assessing the abdomen.

PMID- 19858996
TI  - Winter emergencies: Managing ski and snowboard injuries.

PMID- 19858998
TI  - Patient-education. Dietary supplements.

PMID- 19858999
TI  - 7 tips to improve your professional etiquette.

PMID- 19859000
TI  - Glycemic control in the hospital: how tight should it be?

PMID- 19859002
TI  - The best darn nurse in New Jersey!

PMID- 19859003
TI  - Get a real-world education through simulation.

PMID- 19859004
TI  - Body out of balance: understanding metabolic acidosis and alkalosis.

PMID- 19859005
TI  - Protect your patient from dialysis hypotension.

PMID- 19859006
TI  - Mission control: man aging atrial fibrillation.

PMID- 19859008
TI  - Keep an eye out for contact lens problems.

PMID- 19859009
TI  - Combination drugs...

PMID- 19859010
TI  - Thyroid storm.

PMID- 19859013
TI  - Secular variation in United States rotavirus disease rates and serotypes:
      implications for assessing the rotavirus vaccination program.
AB  - BACKGROUND: Since 2006, we have conducted population-based surveillance for
      rotavirus disease in children seen in hospitals and emergency departments (EDs)
      in Monroe County, NY (Rochester), Hamilton County, OH (Cincinnati), and Davidson
      County, TN (Nashville). METHODS: During the 2006 and 2007 rotavirus seasons,
      clinical information and stool specimens were obtained from county children who
      were <3 years presenting with diarrhea and/or vomiting to the hospital or ED of
      the only children's hospital in each county. Specimens were tested for rotavirus
      and genotyped, and rates of hospitalization and ED visits were calculated.
      RESULTS: While aggregate rotavirus hospitalization rates for the 3 sites were
      similar in 2006 and 2007 (22.5/10,000 and 26.8/10,000, respectively), individual
      rates for the 3 counties differed considerably. The rotavirus hospitalization
      rate in Rochester between 2006 and 2007 increased 3-fold, but decreased by 33% in
      Cincinnati and 41% in Nashville over the 2 study years. G1 strains accounted for
      >80% of strains at all 3 sites in 2006. However, in 2007, the uncommon P[8], G12
      strain was detected in 69% of Rochester specimens, while the P[8], G1 strain
      remained predominant in the other 2 sites. No subjects received rotavirus vaccine
      in 2006 and coverage with 2 to 3 vaccine doses reached 15% in all 3 communities
      by June 2007. CONCLUSIONS: During the 2006 and 2007 rotavirus seasons, with only
      limited vaccine use, remarkable variability was observed in the population-based
      rates of severe rotavirus and in the rotavirus serotypes across the 3 sites. This
      natural secular variability in rotavirus disease must be considered in the
      assessment of the impact of vaccine on disease rates and rotavirus serotypes.

PMID- 19859014
TI  - Cefepime and mortality in pediatric acute myelogenous leukemia: a retrospective
      cohort study.
AB  - BACKGROUND: Based on 2 meta-analyses, the Food and Drug Administration issued a
      communication in 2009 regarding the potential risk of death in patients treated
      with cefepime. Pediatric patients with acute myelogenous leukemia (AML) have
      frequent episodes of fever necessitating the use of antibiotics such as cefepime.
      We evaluated the association of cefepime and other beta-lactam antibiotic
      exposures with all cause in-hospital mortality in pediatric AML patients.
      METHODS: We performed a retrospective cohort study using the Pediatric Health
      Information System, an inpatient database. Exposure to cefepime, ceftazidime,
      antipseudomonal penicillin, and carbapenems was evaluated for each 30-day period
      within the first year from AML diagnosis. Cox regression analysis was used to
      compute hazard ratios (HR) for death adjusting for demographics, clinical
      variables, and clustering by hospital. The final analysis used 2 distinct time
      periods (0-3 months and >3-12 months) to account for variation in proportional
      hazards over time. RESULTS: No differences between the HRs for mortality were
      observed for the time period of 0 to 3 months (cefepime vs. ceftazadime: HR=1.33,
      95% CI: 0.70-2.52; cefepime vs. antipseudmonal penicillin: HR=0.86, 95% CI: 0.34
      2.13; and cefepime vs. carbapenems: HR=1.08, 95% CI: 0.50-2.35) or the time
      period of >3 to 12 months after diagnosis (cefepime vs. ceftazadime: HR=1.29, 95%
      CI: 0.53-3.15; cefepime vs. antipseudomonal penicillin: HR=1.08, 95% CI: 0.44
      2.66; and cefepime vs. carbapenems: HR=1.03, 95% CI: 0.45-2.33). CONCLUSIONS: In
      this cohort of pediatric AML patients, cefepime exposure in the 30 days preceding
      death did not result in an increased mortality risk when compared with
      ceftazidime, antipseudomonal penicillins, or carbapenems.

PMID- 19859015
TI  - Nasopharyngeal acute phase cytokines in viral upper respiratory infection: impact
      on acute otitis media in children.
AB  - BACKGROUND: The role of acute phase cytokines generated in the nasopharynx during
      viral upper respiratory infection (URI) in subsequent development of acute otitis
      media (AOM) has not been examined. METHODS: We studied 326 virus-positive URI
      episodes in 151 children aged 6-36 months. Nasopharyngeal secretions collected
      within 1 to 7 days of URI onset were studied for viruses by conventional and
      molecular techniques, and for concentrations of IL-1beta, IL-6, and TNFalpha by
      multiplex enzyme-linked immunosorbent assay. Children were followed up for 28
      days to document AOM complication. RESULTS: IL-1beta, IL-6, and TNFalpha
      concentrations correlated positively with each other (P<0.001). IL-6 and TNFalpha
      concentrations were higher in males than in females (P=0.01 and 0.02). IL-6 and
      TNFalpha concentrations were inversely correlated with age (P=0.02 and 0.05). IL
      6 concentrations correlated positively with duration of fever (P=0.006) and
      correlated negatively with the number of days of URI symptoms (P=0.026).
      Furthermore, IL-6 concentrations were significantly higher during adenovirus and
      influenza virus URIs as compared with enterovirus and rhinovirus URIs (P<0.01).
      IL-1beta concentrations were higher during URI episodes with AOM than those
      without AOM (P<0.001). CONCLUSIONS: We found IL-6 nasopharyngeal secretions
      concentrations to be higher with adenovirus and influenza infection, and in
      children with systemic febrile response during URI. However, IL-1beta was found
      to play a more important role in the development of AOM after URI. Additional
      studies are needed to further define the role of acute phase cytokines in virus
      induced AOM.

PMID- 19859016
TI  - Chagas disease as a cause of symptomatic chronic myocardopathy in Mexican
      children.
AB  - We report the first case series of children in Mexico living with symptomatic
      Chagas disease causing chronic myocardopathy. The findings suggest that children
      with Chagas disease may develop symptomatic chronic myocardopathy earlier than
      previously recognized. Our findings emphasize the importance of longitudinal
      cardiologic follow-up of all children identified with acute Chagas disease.In a
      cohort of 826 children from the state of Queretaro in Mexico, 11 were identified
      with positive serology (ELISA and IFI) for Chagas and were tested for
      electrocardiogram alterations and symptoms and signs. Four children had ECG
      alterations with 3 of these reporting signs and symptoms associated with the
      chronic phase of Chagas disease (27%; 95% CI: 6%-61%). The most common chronic
      symptom was chest pain, with one child also reporting dyspnea and tachycardia.

PMID- 19859017
TI  - World arboviruses: the Bunyaviridae.

PMID- 19859018
TI  - Diagnosis and management of central venous catheter-related bloodstream
      infections in pediatric patients.

PMID- 19859019
TI  - Myocardial abscess and bacteremia complicating Mycobacterium fortuitum pacemaker
      infection: case report and review of the literature.
AB  - A case of pacemaker infection complicated by bacteremia and myocardial abscess
      caused by Mycobacterium fortuitum is reported and 9 other cases of pacemaker
      infection associated with rapidly growing mycobacteria are reviewed. Most cases
      developed within 6 months from implantation suggesting nosocomial acquisition.
      Wound discharge, fever, and pain at generator site were the most common
      presenting features. At presentation they had a median duration of symptoms of 34
      days. Concomitant bacteremia was present in half of the cases. Antibiotics
      therapy and removal of the pacemaker system were needed to achieve cure in the
      majority of cases. Clarithromycin and fluoroquinolones were the most commonly
      used antibiotics.

PMID- 19859020
TI  - Human bocavirus DNA detected in a boy with plastic bronchitis.

PMID- 19859021
TI  - Brain abscesses due to Citrobacter koseri in a pair of twins.

PMID- 19859022
TI  - Linezolid an oral treatment option for staphylococcal liver abscess in chronic
      granulomatous disease.

PMID- 19859023
TI  - Yellow fever vaccination and Kawasaki disease.

PMID- 19859024
TI  - Evaluation of sensitivity and specificity of rapid influenza diagnostic tests for
      novel swine-origin influenza A (H1N1) virus.

PMID- 19859025
TI  - Sex-specific interaction between MAOA promoter polymorphism and Apo epsilon 2
      allele in major depressive disorder in the Chinese population.

PMID- 19859026
TI  - Association between APOE polymorphisms and predisposition for autism.

PMID- 19859027
TI  - Association between testing for human immunodeficiency virus and changes in risk
      behaviors among injecting drug users in southern China: partial retraction.

PMID- 19859035
TI  - Laparoscopic gastrectomy for treatment of advanced gastric cancer: preliminary
      experience on 38 cases.
AB  - AIM: In the last 20 years the laparoscopic surgery rapidly and successfully
      diffused for the treatment of benign diseases and recently also for the treatment
      of malignancy; newerteless, the laparoscopic gastrectomy for gastric cancer is
      still controversial, in relation to extreme difficulty of a radical surgical
      resection performing with an accurate lymphadectomy. The authors present a
      surgical experience of patients affected by advanced gastric cancer who underwent
      total or subtotal gastrectomy with videoassisted or entirely laparoscopic
      technique in order to evaluate the safety, feasibility, advantages and limits of
      this surgical approach. METHODS: between January 2002 and August 2007 we
      performed 40 laparoscopic procedure for advanced gastric cancer; of these, 38
      (95%) patients underwent a laparoscopic gastric resection and 2 (5%) patients
      underwent a palliative surgical treatment (laparoscopic gastro-entero
      anastomosis). In the 38 patients which underwent laparoscopic gastrectomy, the
      anatomical localization of cancer, ASA score, pTNM classification, type of
      surgical laparoscopic technique (videoassisted or entirey laparoscopic
      technique), mean number of lymph nodes harvested, mean operative time, rate of
      conversion, postoperative morbidity and mortality and rate of local recurrence at
      24 mounths follow-up were retrospectively analyzed. RESULTS: Thirty-eight
      laparoscopic gastrectomies for gastric cancer were performed: in relation to
      surgical technique, 4 (10.5%) of these were video-assisted gastric resection
      (left subcostal minilaparotomy and extracorporeal anastomosis) and 34 (89.5%)
      were entirely laparoscopic gastrectomy; regarding to extension of surgical
      resection, there were 16 (42%) total D2 gastrectomies and 22 (58%) subtotal
      gastrectomies, of which 19 D2 gastrectomy and 3 D1 gastrectomy. Regarding the ASA
      score, 23% of patients were in ASA I, 52% in ASA II, 25% in ASA III. The mean
      operative time was 225 minutes (range 160-285) for total gastrectomy and 183
      minutes (range 70-270) for subtotal gastrectomy. Overall, on 38 laparoscopic
      gastric resection, the conversion rate was 7.8% (3 patients). The number of lymph
      nodes harvested was 28 (range 5-53). No major intraoperative complications were
      observed. Overall morbidity was 31.5% (12 patients); the rate of postoperative
      surgical complications was 8% (3 patients). One patient (2.6%) dead for a sepsis
      subsequent to leak of esophagojejunal anastomosis. Mean hospital stay was 16 days
      for total gastrectomies and 12 days for subtotal gastrectomies. Three cases
      (7.9%) of cancer recurrence were observed in 3 patients (2 patiens UICC IIIa, one
      patient UICC IIIb) at 20th, 23th, 24th postoperative month and one case (2.6%) of
      peritoneal carcinosis at 18th month. No port-site metastasis were observed at 24
      month follow-up. CONCLUSIONS: On the basis of this surgical preliminary
      experience, laparoscopic gastrectomy for malignancy resulted a technically safe
      surgical procedure if performed by an advanced laparoscopic surgical team, with
      additional benefits, time to resumption of oral intake, morbidity rate, and
      acceptance from patients. A radical laparoscopic gastrectomy via laparoscopic
      approach is advisable until UICC stage II, in patients with ASA score I-III and
      minimal endoabdominal adhesion. The safe and efficacy of laparoscopic treatment
      in locoregional limph nodes dissection is still controversial. However, long-term
      results of prospective and comparative trials will be necessary to show the real
      oncologically benefits of laparoscopic approach.

PMID- 19859036
TI  - [Adjuvant chemotherapy after radical liver resection in the treatment of
      metastases from colorectal carcinoma].
AB  - Liver metastases are the leading cause of death in patients with colorectal
      carcinoma: approximately 25% present with metastases at diagnosis of the primary
      tumor and 30-50% will eventually develop metastases. Surgical therapy for
      metastases is the only curative treatment that will ensure five-year survival in
      30-60% of patients; however, in 30-50% of these patients liver disease will
      recur. To improve these rates, various different studies have investigated the
      efficacy of postsurgical adjuvant therapy. The majority of randomized studies
      evaluated the efficacy of intra-arterial infusion associated or not with
      postsurgical systemic adjuvant treatment: this approach demonstrated benefit in
      terms of control of recurrent of liver disease but not in terms of overall
      survival. A reduction in the recurrence of liver disease was found in the two
      randomized studies published to date on the efficacy of systemic adjuvant
      therapy, and an improvement in survival in one trial. Given these data and the
      results obtained with the use of last generation chemotherapeutic agents
      (oxaliplatin and irinotecan) in the treatment of unresectable liver metastases
      from colorectal carcinoma, it can be conjectured that ongoing randomized clinical
      trials may confirm a significant advantage of adjuvant chemotherapy in the
      control of recurrence of liver disease and overall survival.

PMID- 19859037
TI  - Surgical options in the management of pancreatic cancer.
AB  - Management of pancreatic cancer is an interdisciplinary challenge as this tumor
      entity is still characterized by a poor prognosis and an overall long-term
      survival of only 1-5%. From the oncological dimension, pancreatic cancer
      represents the fourth leading cause of cancer related mortality in the Western
      world with more than 100000 deaths in Europe and the USA per year. A major
      problem is the early detection since 80-90% of pancreatic cancers are locally or
      systemically advanced at the time of diagnosis. However, in patients who are
      suitable for resection five-year survival rates of about 25% are observed, which
      underlines that surgery offers the only chance of potential cure and long-term
      survival. Yet, surgical therapy has to be embedded in an oncological concept of
      adjuvant treatment as postoperative chemotherapy is a key factor to further
      improve patient survival. Numerous ongoing studies on new therapeutic agents like
      antibodies, antimetabolites and supportive agents reflect the current scientific
      and clinical struggle to achieve better outcome of pancreatic cancer patients in
      the future on the basis of initial tumor resection or if this is not possible as
      a palliative treatment. Standard resections include partial pancreatico
      duodenectomy with distal gastric resection or recently accepted as the preferable
      procedure preservation of the pylorus for tumors in the head of the pancreas,
      distal pancreatectomy for tumors of the corpus and tail as well as total
      pancreatectomy for more extended tumors or intraductal papillary mucinous
      neoplasias if necessary. Venous resections including the portal and superior
      mesenteric vein during these procedures are well-accepted, while resection of
      arterial vessels, metastases or recurrent disease are not considered as standard
      procedures and should therefore only be performed for special indications and in
      selected patients. Today, standardization of surgical procedures and
      centralization of pancreatic surgery in high volume institutions guarantees best
      patient care and mortality rates below 5%.

PMID- 19859038
TI  - Management of intraductal papillary mucinous neoplasms of the pancreas.
AB  - Over the last decade, the diagnosis and treatment of intraductal papillary
      mucinous tumors (IPMN) of the pancreas has evolved. They represent a spectrum of
      disease, ranging from benign to malignant lesions, making the early detection and
      characterization of these lesions important. Several non-invasive and invasive
      imaging modalities allow adequate visualization of these lesions. Multidetec-tor
      computed tomography (MCT) and magnetic resonance (MR) Cholangiopan-creatography
      are generally used as fist line imaging techniques, whereas invasive techniques
      as endoscopic ultrasound or endoscopic retrograde cholangiopancreatography are
      usually considered in the setting of an uncertain diagnosis. Multiple factors
      have to be taken into consideration in order to establish an adequate management
      of these lesions. Main duct and combined IPMN, as well as branch duct lesions
      larger than 3 cm or containing aggressive features as solid component are
      considered indications for surgical resection. On the other hand, follow-up
      through imaging is advocated for small, benign appearing lesions, as well as for
      post-surgical patients. In the later setting, the follow-up protocol should
      consider the aggressiveness of the resected lesion and the surgical margins, in
      order to establish an optimal time interval of imaging.

PMID- 19859040
TI  - Targeted therapies for pancreatic adenocarcinoma.
AB  - The majority of patients diagnosed with adenocarcinoma of the pancreas have
      advanced disease at presentation, with only 20% surviving beyond one year. Even
      among the 10% to 15% of patients who present with localized disease, only 20%
      will be alive 5 years post surgical resection. Systemic therapy for pancreatic
      adenocarcinoma to date has failed to provide more than a very modest survival
      benefit for patients with advanced disease. However, the past decade has seen
      significant advances in the understanding of the molecular pathogenesis of
      pancreatic cancer, culminating in the sequencing of the pancreatic cancer genome.
      New generations of therapeutic agents targeting key oncogenic cellular signaling
      pathways are currently under evaluation in advanced pancreatic adenocarcinoma.
      Although thus far only erlotinib has been shown to improve survival when compared
      to gemcitabine monotherapy, the authors anticipate that further developments in
      biomarker analysis and pharmacogenomics, along with the identification of new
      drugs will help maximize the benefit of novel therapeutics by directing effective
      use in the future. Herein the authors review the evidence to date for the use of
      novel cytotoxic and molecularly targeted agents in pancreatic adenocarcinoma, and
      discuss key areas for future therapeutic development.

PMID- 19859039
TI  - Pancreatic cancer stem cells and EMT in drug resistance and metastasis.
AB  - Pancreatic cancer (PC) is an aggressive malignancy with one of the worst outcomes
      among all cancers. It is the fourth leading cause of cancer death in the United
      States with a very low five-year survival rate. The high mortality of PC could,
      in part, be due to their drug resistance characteristics and high propensity for
      metastasis. Recently, cancer stem cells (CSCs) and epithelial-mesenchymal
      transition (EMT)-type cells, which shares molecular characteristics with CSCs,
      have been believed to play critical roles in drug resistance and cancer
      metastasis as demonstrated in several human malignancies including PC. Thus, the
      discovery of molecular knowledge of drug resistance and metastasis in relation to
      CSCs and EMT in PC is becoming an important area of research, and such knowledge
      is likely to be helpful in the discovery of newer drugs as well as designing
      novel therapeutic strategies for the treatment of PC with better outcome. In this
      brief review, we will summarize the current knowledge regarding the CSCs and EMT
      in the context of drug resistance and metastasis in PC, the molecular events
      occurring in CSCs and EMT, and the design of novel therapeutic strategies
      targeting CSCs and EMT-type cells to increase drug sensitivity and suppression of
      metastasis toward better treatment outcome of patients diagnosed with PC.

PMID- 19859041
TI  - Clinically-relevent orthotopic metastatic models of pancreatic cancer imageable
      with fluorescent genetic reporters.
AB  - This article describes authors' cumulative experience with the development and
      preclinical application of clinically-relevant, metastatic orthotopic mouse
      models of pancreatic cancer made imageable with genetic reporters. These models
      utilize the human pancreatic cancer cell lines which have been genetically
      engineered to selectively express high levels of green fluorescent protein (GFP)
      or red fluorescent protein (RFP). Tumors with fluorescent genetic reporters are
      established subcutaneously in nude mice, and fragments of the subcutaneous tumors
      are then surgically transplanted onto the pancreas. Loco-regional tumor growth
      and distant metastasis of these orthotopic implants occurs spontaneously and
      rapidly throughout the abdo-men in a manner consistent with clinical human
      disease. Highly specific, high-resolution, real-time quantitative fluorescence
      imaging of tumor growth and metastasis may be achieved in vivo without the need
      for contrast agents, invasive techniques, or expensive imaging equipment. A high
      correlation between florescence optical imaging, magnetic resonance imaging, and
      ultrasound in these models has been demonstrated. Transplantation of RFP
      expressing tumor fragments onto the pancreas of GFP- or cyan fluorescent protein
      expressing transgenic mice was used to facilitate visualization of tumor-host
      interaction between the pancreatic cancer cells and host-derived stroma and
      vasculature. Such in vivo models have enabled visualization in real time and
      acquisition of images of the progression of pancreatic cancer in the live animal,
      the models also demonstrate the real-time antitumor and antimetastatic effects of
      several novel therapeutic strategies on pancreatic malignancy. These fluorescent
      models are therefore powerful and reliable tools with which to investigate
      metastatic human pancreatic cancer and novel therapeutic strategies directed
      against it.

PMID- 19859042
TI  - [Unusual location of peritoneal inclusion cysts].
AB  - The peritoneal inclusion cyst is a rare, probably congenital, pathology of the
      mesothelium that develops on coelomatic residues. A case is reported of an
      unusual location of peritoneal cyst, in which the increase in volume, associated
      with the patient's concern and the presumed anatomic site of the lesion led to
      its removal by the laparoscopic route. The type of location and the relative
      inaccuracy of preoperative imaging are discussed.

PMID- 19859043
TI  - Prevalence, clinical significance and prognostic value of anti-thyroglobulin
      antibodies in the follow-up of patients with differentiated thyroid carcinoma: a
      retrospective study.
AB  - AIM: Elevated persistent value of antithyroglobulin antibodies (Ab-Tg) in
      differentiated thyroid carcinoma (DTC) patients may interfere with Tg
      determination. The aim of the study was to evaluate the use of Ab-Tg as tumor
      marker as a replacement for thyroglobulin (Tg). METHODS: From 1990 al 2004 767
      patients have been treated and followed, mean follow-up years 6.9+/-2.4. Thirty
      two patients Ab-Tg positive after radioiodine ablation, who had showed during the
      follow-up stable indosable value di Tg, have undergone analysis. RESULTS: The
      recurrences were statistically more significant when Ab-Tg were increased, than
      when Ab-Tg were stable or diminished during the time (P<0.0001). Lymphocytic
      thyroditis was found in thirteen patients (40.6%) at histological specimen after
      thyroidectomy. The persistence of lymphocytic thyroditis has not modified the
      value of Ab-Tg as tumor marker (P<0.001). The 10/32 (31.2%) patients Tg negative
      have been compared to the 61/712 patients Ab-Tg positive (8.6%) who relapse. The
      recurrence rate was significantly higher for the first group of patients than
      that for the second (P<0.0001). Multivariate analisys showed N1 (P<0.001; OR
      2.51) and Ab-Tg positive (P<0.001; OR: 6.15) associated with recurrences.
      CONCLUSIONS: Ab-Tg must be determined, in concomitance with Tg, during the follow
      up of DTC, to establish the accuracy of Tg, in order to use it as tumour marker.
      It must be kept in mind that the strongest indication for relapse due to Ab-Tg is
      an increasing of level in the same patient measured in the long time. Persistent
      elevated Ab-Tg levels are prognostic of future recurrences.

PMID- 19859044
TI  - Cardiovascular risk stratification of diabetic patients.
AB  - Diabetes mellitus is a complex clinical entity that will grow in importance in
      the future. The complications of diabetes have a significant impact on patient
      survival and quality of life, particularly with respect to coronary artery
      disease (CAD). Appropriate screening and aggressive intervention can
      significantly benefit many patients with diabetes. In addition, it is important
      to consider strategies useful not only in the diagnosis of CAD but also in the
      prognostic evaluation of diabetic patients with coronary disease. Prognostic data
      are essential in defining risk categories and to apply appropriate treatment for
      the degree of risk. Therefore, accurate cardiovascular risk stratification of
      patients with type 2 diabetes is required. However, this can be a problematic
      issue because the clinical presentation and progression of CAD differs between
      diabetic and nondiabetic subjects. In addition to a higher prevalence of CAD,
      patients with diabetes experience more diffuse and extensive coronary artery
      involvement, more often have left ventricular dysfunction, a more advanced
      coronary disease at the time of diagnosis, and more often experience silent
      ischemia. Furthermore, diabetic patients have frequently a less favorable
      response to revascularization procedures and a poorer long-term outcome. The
      purpose of this review is to discuss the relative role of various procedures for
      diagnosis of CAD and for cardiac risk stratification in patients with diabetes.

PMID- 19859045
TI  - Multiorgan dysfunctions in diabetic patients: the role of functional imaging.
AB  - Functional imaging plays a central role in the evaluation of some of the clinical
      problems faced by diabetic patients. In cardiovascular disease, myocardial
      perfusion imaging, particularly when complemented by gated SPECT, is a powerful
      tool not only for establishing the diagnosis of coronary artery disease, but also
      for providing prognostic information in both the general and diabetic
      populations. Although promising, its role in screening of asymptomatic diabetic
      patients is yet to be established, and its role as a potential 'one-stop shop'
      also needs further study. PET is currently the gold standard for viability
      assessment, and also provides prognostic data, but its widespread use is limited
      by cost and availability. Hybrid imaging with PET/CT is promising, and could
      revolutionise cardiac imaging by combining functional and anatomic information.
      In the investigation of the diabetic foot, labelled leukocyte imaging is the
      nuclear medicine test of choice to diagnose osteomyelitis. It is likely that
      SPECT/CT will further improve diagnostic accuracy, but more studies are needed.
      Combined leukocyte and bone marrow imaging is of value in distinguishing
      osteomyelitis from neuropathic osteoarthropathy in the diabetic foot; PET and
      PET/CT may also be of value in these cases, but their wider role is currently
      inconclusive. The value of bone scintigraphy in the diabetic foot, even as a
      screening test, is questionable. Functional imaging methods can also be employed
      in the evaluation of other diabetic complications, including the assessment of
      left ventricular function, renal scarring and gastric emptying, but these methods
      are not widely used in current clinical practice.

PMID- 19859046
TI  - Diabetes and bone: advantages and limitations of radiological, radionuclide and
      hybrid techniques in the assessment of diabetic foot.
AB  - A common cause of morbidity and mortality in diabetic patients are foot
      infection/complications often leading to amputation of lower extremities. Various
      radiological and radionuclide techniques are available for the assessment of
      diabetic patients with bone or soft tissue infections. However, there are several
      advantages and limitations. The major limitation of all these techniques is their
      inability to accurately differentiate osteomyelitis from charcot's/neuropathic
      joints. Radiologically, magnetic resonance imaging (MRI) is the technique of
      choice and a radiolobeled white cell scan is a useful nuclear medicine technique
      in the evaluation of diabetic patients with suspected foot infection. In this
      review we discuss the efficacy of radiological and radionuclide techniques in the
      assessment of diabetic foot infection.

PMID- 19859047
TI  - Osteoporosis: recent physiopatologic acquisitions and new therapeutic
      perspectives.
AB  - The World Health Organization (WHO) declared osteoporosis "social disease". The
      present revision of the literature will focus on the recent acquisitions in bone
      pathophysiology and the efforts in the formulation of new molecules able to
      change successfully the course of the disease. Osteocyte cell is now thought to
      be the main biomechanical transducer of bones, able to release sclerostin that
      produces inhibition on osteosynthesis and on the other hand to release substances
      like nitrid oxide and prostaglandins that provide a stimulus to osteosynthesis
      through direct or indirect activation of osteoblasts. In this work the authors
      analyze the most important clinical trials involving the use of new molecules,
      like denosumab, integrin avb3 inhibitor, cathepsin k inhibitors, able to
      interfere in the new osteometabolic pathways. Two trials, phase I and II, have
      been conducted using denosumab. The endpoint of the first phase was the
      evaluation of the markers of resorption and bone formation, while the second
      phase II trial focused on the use of this molecule in double-blind matching
      placebo and open alendronate with the evaluation of bone mass density (BMD) over
      one year in lumbar area. Another clinical trial in double-blind versus placebo
      was carried on and published on the use of a competitive integrin avb3 inhibitor
      in various dosages for the evaluation of bone mass modification in the lumbar and
      femoral area and of bone markers modification. Many studies focus on the use of
      cathepsin k inhibitors. Odanacatib has demonstrated to have worked on dose
      dependent increase of densitometric value and to have reduced the bone turnover.

PMID- 19859048
TI  - The role of nuclear medicine technique in evaluating electrophysiology in
      diabetic hearts especially with 123I-MIBG cardiac SPECT imaging.
AB  - Diabetes mellitus is a risk factor for cardiovascular morbidity and death.
      Cardiac autonomic diabetic neuropathy (CADN) is a common and serious complication
      of diabetes mellitus, which consists of damage to the autonomic nerve fibres that
      innervate the heart and blood vessels, resulting in alterations in heart rate
      control and vascular dynamics, associated with disabling clinical manifestations
      and increased mortality and incidence of both silent myocardial ischaemia and
      infarction. In vivo non-invasive radionuclide assessment of cardiac sympathetic
      innervation is possible with the use of radioabelled analogues of norepinephrine,
      which are actively taken up by the postganglionic presynaptic sympathetic nerve
      fibres of the heart. The catecholamine analogue 123I-metaiodobenzylguanidine
      (123I-MIBG) is the most commonly used tracer for imaging myocardial presynaptic
      sympathetic innervation on a broad clinical basis. 123I-MIBG imaging provides
      unique insights into the effects of diabetes on cardiac sympathetic integrity and
      the pathophysiological consequences of cardiac sympathetic dysinnervation. It
      also allows the assessment of both glycemic control on the progression of
      autonomic neuropathy and the effects of the autonomic derangement on myocardial
      blood flow regulation, function and electrophysiology, showing even potential for
      the prediction of adverse outcome.

PMID- 19859049
TI  - Expanding criteria for peritoneal dialysis use.
AB  - The end stage renal disease population is growing all around the world. Most of
      these patients will need any kind of renal replacement treatment: renal
      transplantation, hemodialysis or peritoneal dialysis. Treatment of renal failure
      is costly and many analyses demonstrate that home based dialysis is the cheapest.
      In spite of social, clinical and economical advantages of peritoneal dialysis
      (PD), it is an underutilized modality of renal treatment. Low incidence and
      prevalence of PD as a renal replacement therapy is still a truth. Many factors
      influence that scarce use; nowadays there are countries which are making changes
      in their health systems in an effort to enhance its use. The following review
      presents the current situation of the use of peritoneal dialysis, its costs,
      complications and possible improvements to enhance its use.

PMID- 19859051
TI  - The role of nutritional status in the outcome of peritoneal dialysis patients.
AB  - Abnormalities in nutritional status of peritoneal dialysis (PD) patients include
      too high body mass (overweight, obesity), too low body mass (underweight,
      starvation) or changes in body composition (malnutrition) without or with normal
      body weight. In vivo neutron activation analysis is considered the reference gold
      standard for the determination of protein malnourishment in end-stage renal
      disease patients, but body mass index (BMI) is the most frequently used parameter
      in nutritional assessment surveys. The association between BMI and outcome of PD
      patients is controversial, but so-called obesity paradox (the higher BMI the
      longer survival) remains frequently reported. The use of metabolic syndrome with
      high BMI as a crucial component is not more predictable in the prognosis of
      outcome in PD patients than using separately each risk factor of metabolic
      syndrome. Underweight/starvation is univocally underlined as associated with
      morbidity and mortality, but prevalence of severe undernutrition is decreasing
      over last decades, at least in well developed countries. PD patients may also
      present features of malnutrition without decreased body mass or even with
      increased body weight. It mainly concerns to deficiencies of vitamins, minerals
      and trace elements. Serum albumin concentration has serious limitations as a
      marker of nutritional status, because is influenced by volemic status and
      inflammation. Nutritional interventions in undernourished patients (oral,
      intestinal or intravenous feeding, amino acid peritoneal solution,
      supplementation of vitamins and trace elements) may correct deficiencies, but
      their influence on PD patients survival remains unclear.

PMID- 19859050
TI  - Cardiovascular disease in peritoneal dialysis patients.
AB  - Patients on peritoneal dialysis have a high level of morbidity and mortality
      associated with atherosclerotic cardiovascular disease and they also have an
      increased risk of sudden death. The atherosclerosis seen in peritoneal dialysis
      patients is associated with both traditional cardiovascular risk factors such as
      low levels of physical activity, hyperlipidemia, hypertension, diabetes and
      smoking as well as non-traditional risk factors such as elevated oxidative stress
      and inflammation. The atherosclerosis may be preceded by endothelial dysfunction
      and increased arterial stiffness. Measures of arterial stiffness such as aortic
      pulse wave velocity predict morbidity and mortality. Numerous studies have
      reported that the elevated levels of oxidative stress and inflammation in this
      population are associated with arterial stiffness and in turn with the
      development of cardiovascular disease. A number of studies have reported that
      peritoneal dialysis is associated with lower levels of oxidative stress and
      inflammation compared to haemodialysis. A small number of trials have extended
      this work to determine associations between oxidative stress and inflammation
      with vascular or myocardial structure and function with equivocal results. The
      decision to undergo either peritoneal or haemodialysis is based on many factors
      which include the differential damage the renal replacement therapy may have on
      the cardiovascular system. Current evidence suggests this may vary over time.
      Previous randomised controlled trials and many other observational studies have
      produced conflicting results as to which therapy may have a cardiovascular
      advantage. Some registry data suggests peritoneal dialysis is associated with a
      lower mortality than haemodialysis in the first one-two years but thereafter may
      be higher on peritoneal dialysis than haemodialysis. Other registry data do not
      support this. Further long-term studies assessing surrogate and hard endpoint
      cardiovascular outcomes in peritoneal dialysis are required.

PMID- 19859052
TI  - Metabolic consequences of peritoneal dialysis treatment.
AB  - Energy and protein metabolism are both altered in chronic kidney disease (CKD)
      from its early stages. Patients undergoing peritoneal dialysis (PD) use
      peritoneal solutions with glucose as osmotic agent, which exposes them to an
      increased glucose load (40-80 g/day) and during PD there is a net loss of
      proteins through the peritoneum (4-8 g/day). Insulin resistance may lead to a
      reduction of the anabolic effects of insulin, while its proliferative effects on
      adipose tissue are potentially enhanced. Insulin resistance is also an important
      factor in the development of hypertriglyceridemia in PD patients: it increases
      free fatty acid availability, which then stimulates the release of large
      triglyceride-rich VLDL. Moreover, inhibitors of lipolytic enzymes (apoC-III,
      inflammation, oxidative modification and carbamoylation of apolipoproteins) may
      reduce lipid clearance, contributing to the development of dyslipidemia.
      Inflammatory molecules also play an important role in regulating glucose
      metabolism, and the excessive activation of inflammatory pathways may represent a
      fundamental step in the development of insulin resistance, including an over
      expression of cytokines. Frequently, protein intake is reduced in PD because of
      under-dialysis, glucose load, abdominal discomfort and abnormal hormones levels,
      leading to a complex "protein-energy malnutrition". Optimization of dialysis
      dose, correction of acidosis and anemia and nutritional counseling, together with
      "non-traditional" management strategies, such as the use of PD solutions without
      glucose, like icodextrin and amino acid based solutions, represent the best
      strategies to prevent and correct malnutrition in PD patients. The mainstay of
      therapy is a reduction of glucose-based PD solutions and a correct dietary
      prescription.

PMID- 19859053
TI  - The use of IFN-alpha in subjects with liver transplant for hepatitis C.

PMID- 19859054
TI  - How many patients with HCC have normal des-gamma-carboxy prothrombin and alpha
      fetoprotein levels?

PMID- 19859055
TI  - Platelet adhesion and aggregation under flow using microfluidic flow cells.
AB  - Platelet aggregation occurs in response to vascular injury where the
      extracellular matrix below the endothelium has been exposed. The platelet
      adhesion cascade takes place in the presence of shear flow, a factor not
      accounted for in conventional (static) well-plate assays. This article reports on
      a platelet-aggregation assay utilizing a microfluidic well-plate format to
      emulate physiological shear flow conditions. Extracellular proteins, collagen I
      or von Willebrand factor are deposited within the microfluidic channel using
      active perfusion with a pneumatic pump. The matrix proteins are then washed with
      buffer and blocked to prepare the microfluidic channel for platelet interactions.
      Whole blood labeled with fluorescent dye is perfused through the channel at
      various flow rates in order to achieve platelet activation and aggregation.
      Inhibitors of platelet aggregation can be added prior to the flow cell experiment
      to generate IC50 dose response data.

PMID- 19859056
TI  - Omentectomy, visceral fat, and insulin resistance.

PMID- 19859057
TI  - Genetic variation in the FAAH gene and metabolic syndrome-related phenotypes.

PMID- 19859058
TI  - Copper deficiency after gastric bypass surgery.

PMID- 19859059
TI  - Response to "Obesity and treadmill exercise duration in Hazmat candidates".

PMID- 19859061
TI  - A biomedical adventurers' guide to navigating between careers in academia and
      industry.
AB  - An explosion of scientific and technological advances has broadened the field of
      biomedicine. Traditional boundaries between the public and private research
      sectors are now blurred by multidisciplinary projects and the necessity for new
      and more efficient models of the translational process. This allows the
      adventurous scientist to boldly and consciously sample selected skills during
      periods of secondment in different institutions and organizations, and to
      assemble a personal and unique blend of competences to help them manage their
      career.

PMID- 19859062
TI  - Induced pluripotent stem cells and reprogramming: seeing the science through the
      hype.
AB  - No-one can have failed to notice the splash that induced pluripotent stem (iPS)
      cells have made in the few years since somatic cells were first reprogrammed to
      pluripotency. But what is their real promise, where should research efforts be
      focused, and are we at a stage where we can replace embryonic stem cells? Four
      pioneering iPS cell researchers offer their personal insights into these and
      other questions of current debate. As well expressing hope for the improved
      understanding and treatment of human disease, they urge caution over safety and
      propose the establishment of iPS cell banks.

PMID- 19859063
TI  - Common disorders are quantitative traits.
AB  - After drifting apart for 100 years, the two worlds of genetics - quantitative
      genetics and molecular genetics - are finally coming together in genome-wide
      association (GWA) research, which shows that the heritability of complex traits
      and common disorders is due to multiple genes of small effect size. We highlight
      a polygenic framework, supported by recent GWA research, in which qualitative
      disorders can be interpreted simply as being the extremes of quantitative
      dimensions. Research that focuses on quantitative traits - including the low and
      high ends of normal distributions - could have far-reaching implications for the
      diagnosis, treatment and prevention of the problematic extremes of these traits.

PMID- 19859064
TI  - Transcriptional control of the inflammatory response.
AB  - Inflammation is a multicomponent response to tissue stress, injury and infection,
      and a crucial point of its control is at the level of gene transcription. The
      inducible inflammatory gene expression programme--such as that triggered by Toll
      like receptor signalling in macrophages--is comprised of several coordinately
      regulated sets of genes that encode key functional programmes; these are
      controlled by three classes of transcription factors, as well as various
      transcriptional co-regulators and chromatin modifications. Here, we discuss the
      mechanisms of and the emerging principles in the transcriptional regulation of
      inflammatory responses in diverse physiological settings.

PMID- 19859065
TI  - Engineering lymphocyte subsets: tools, trials and tribulations.
AB  - Cell-based therapies with various lymphocyte subsets hold promise for the
      treatment of several diseases, including cancer and disease resulting from
      inflammation and infection. The ability to genetically engineer lymphocyte
      subsets has the potential to improve the natural immune response and correct
      impaired immunity. In this Review we focus on the lymphocyte subsets that have
      been modified genetically or by other means for therapeutic benefit, on the
      technologies used to engineer lymphocytes and on the latest progress and hurdles
      in translating these technologies to the clinic.

PMID- 19859067
TI  - Omega-3 fatty acids: cardiovascular benefits, sources and sustainability.
AB  - The evidence for the cardioprotective nature of omega-3 fatty acids is abundant,
      and currently available data indicate that patients with known coronary heart
      disease should consume at least 1 g daily of long-chain omega-3 fatty acids from
      either oily fish or fish-oil supplements, and that individuals without disease
      should consume at least 250-500 mg daily. However, this area of research poses
      two questions. Firstly, which is the best source of omega-3 fatty acids-fish or
      fish-oil supplements? Secondly, are recommendations for omega-3 supplementation
      warranted in view of the rapid depletion of world fish stocks? The argument that
      eating fish is better than taking fish-oil supplements stems from the fact that
      several important nutrients, such as vitamin D, selenium, and antioxidants, are
      missing from the supplements. However, three major prevention trials have clearly
      indicated that omega-3 fatty acid capsules confer cardiovascular benefits and,
      therefore, that both are cardioprotective. Sustainable sources of omega-3 fatty
      acids will need to be identified if long-term cardiovascular risk reduction is to
      be achieved at the population level.

PMID- 19859066
TI  - Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers'
      for clinical trials.
AB  - Rhesus macaques are an important animal model for the study of human disease and
      the development of vaccines against HIV and AIDS. HIV vaccines have been
      benchmarked in rhesus macaque preclinical challenge studies using chimeric
      viruses made up of parts of HIV and simian immunodeficiency viruses. However, the
      lack of efficacy in a recent clinical trial calls for a re-evaluation of the
      scientific assumptions regarding the predictive value of using data generated
      from rhesus macaques as a 'gatekeeper' for the advancement of candidate vaccines
      into the clinic. In this context, there is significant consensus among HIV
      vaccinologists that next-generation HIV vaccines must generate 'better' immunity
      in rhesus macaques than clinically unsuccessful vaccines generated using
      validated assays. Defining better immunity is the core challenge of HIV vaccine
      development in this system and is the focus of this Review.

PMID- 19859068
TI  - Diagnosis and management of pericardial diseases.
AB  - The management of pericardial diseases is largely empirical because of the
      relative lack of randomized trials that involve patients with these conditions. A
      first attempt to bring together and organize current knowledge resulted in the
      publication of the first guidelines on the management of pericardial diseases.
      Nevertheless, a number of observational studies and the first randomized trials
      are moving the management of pericardial diseases towards evidence-based
      medicine, particularly for pericarditis. Emerging data indicate that management
      can be tailored to the individual patient and, although the optimal duration of
      treatment is not clearly established, some recommendations can be formulated to
      guide management and follow-up.

PMID- 19859069
TI  - Mesenchymal stem cells increase hippocampal neurogenesis and counteract
      depressive-like behavior.
AB  - Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential
      candidates for treatment of neurodegenerative disorders, because of their ability
      to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural
      lineages as well as by expressing neurotrophic factors that enhance the survival
      and differentiation of neural progenitor cells. Depression has been associated
      with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the
      aim of this study was to analyze the therapeutic potential of MSCs in the
      Flinders sensitive line (FSL), a rat animal model for depression. Rats received
      an intracerebroventricular injection of culture-expanded and 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow
      derived MSCs (105 cells). MSC-transplanted FSL rats showed significant
      improvement in their behavioral performance, as measured by the forced swim test
      and the dominant-submissive relationship (DSR) paradigm. After transplantation,
      MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the
      hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and
      contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate
      gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated
      with MSC engraftment and behavioral performance. We therefore postulate that MSCs
      may serve as a novel modality for treating depressive disorders.

PMID- 19859070
TI  - Possible renoprotection by vitamin D in chronic renal disease: beyond mineral
      metabolism.
AB  - Vitamin D is typically viewed as a key player in the regulation of calcium and
      phosphate levels and the control of bone metabolism; however, growing evidence
      suggests that vitamin D deficiency may also have an important role in the
      progressive loss of renal function. Vitamin D deficiency is particularly frequent
      in patients with chronic kidney disease, in whom it is associated with increased
      mortality. Studies indicate that treatment with vitamin D analogues reduces
      proteinuria, suppresses the renin-angiotensin-aldosterone system (RAAS), and
      exerts anti-inflammatory and immunomodulatory effects. These pleiotropic effects
      render vitamin D a potentially interesting treatment modality for renoprotection
      in patients with chronic kidney disease. Whether vitamin D has clinically
      relevant renoprotective effects in addition to RAAS blockade is currently under
      investigation.

PMID- 19859071
TI  - An update on the lipid nephrotoxicity hypothesis.
AB  - When the 'lipid nephrotoxicity hypothesis' was proposed in 1982, it brought
      together several disparate experimental findings in hyperlipidemia and renal
      disease to suggest that concomitant hyperlipidemia and proteinuria would cause
      self-perpetuating renal disease once the initial glomerular insult was no longer
      present. This process would be analogous to atherosclerosis. Since 1982,
      increasing evidence has supported the hypothesis that lipid abnormalities
      contribute to both atherosclerosis and glomerulosclerosis. In this Review, we
      discuss research developments that are relevant to the lipid nephrotoxicity
      hypothesis. We describe how inflammatory stress accompanying chronic kidney
      disease modifies lipid homeostasis by increasing cholesterol uptake mediated by
      lipoprotein receptors, inhibiting cholesterol efflux mediated by the ATP-binding
      cassette transporter 1 and impairing cholesterol synthesis in peripheral cells.
      As a result of these events, cholesterol relocates to and accumulates in renal,
      vascular, hepatic and possibly other tissues. The combination of increased
      cellular cholesterol influx and reduced efflux causes injury in some tissues and
      lowers the plasma cholesterol level. In addition, inflammatory stress causes a
      degree of statin resistance via unknown mechanisms. These phenomena alter
      traditional understanding of the pathogenesis of lipid-mediated renal and
      vascular injury and could influence the clinical evaluation of renal and
      cardiovascular risk and the role of lipid-lowering treatment in affected
      patients.

PMID- 19859072
TI  - Application of proteomic analysis to the study of renal diseases.
AB  - Proteomics-based approaches are generating considerable data in clinical
      nephrology covering almost all aspects of the discipline. Proteomic experiments
      commonly involve fractionation and protein separation, followed by mass
      spectrometric analysis to identify proteins and peptides. Biostatistical and
      bioinformatical input is essential in such experiments, from initial experimental
      design to analysis of data. Standardization of procedures is an important
      research objective. Depending on study design, results can lead to biomarker
      discovery, mechanistic insight and identification of potential avenues for
      therapeutic intervention and treatment evaluation. Understanding proteomic
      information and its place in current clinical research and practice is
      fundamental. This Review describes proteomic experimentation and the concepts
      behind it, and gives an overview of its application to important areas in
      clinical nephrology including acute kidney injury, chronic kidney disease, end
      stage renal disease, genetic diseases and fluid and electrolyte disorders, with a
      particular focus on biomarker discovery. The importance of future developments,
      such as the establishment of an infrastructure for a 'biomarker pipeline' with
      structured validation pathways for candidate biomarkers and development of
      clinical assays, is also discussed and some future perspectives are presented.

PMID- 19859073
TI  - Residual microvascular risk in diabetes: unmet needs and future directions.
AB  - The burden of microvascular disease in patients with type 2 diabetes mellitus
      continues to escalate worldwide. Current standards of care reduce but do not
      eliminate the risk of diabetic retinopathy, nephropathy or neuropathy in these
      patients. Correction of atherogenic dyslipidemia, which is characterized by
      elevated triglyceride levels and low levels of HDL cholesterol, might provide
      additional benefit. Whereas promising data have been published with respect to
      fibrate therapy for maculopathy, fenofibrate for diabetic retinopathy, and statin
      or fibrate therapy for diabetic nephropathy, further studies are warranted to
      define optimal management strategies for reducing the residual microvascular
      risk. Such strategies are especially relevant in cases of diabetic peripheral
      neuropathy, where even optimal care fails to affect disease progression.
      Identification of those factors that are most relevant to residual diabetes
      related microvascular risk is a priority of an ongoing multinational
      epidemiological study. In this Review, we highlight an urgent need to address the
      issue of microvascular residual risk in patients with or at risk of type 2
      diabetes mellitus.

PMID- 19859075
TI  - What predicts obesity in patients with rheumatoid arthritis? An investigation of
      the interactions between lifestyle and inflammation.
AB  - OBJECTIVE: To assess whether physical activity, diet or inflammation is a more
      important determinant of body mass index (BMI) and body fat (BF) in patients with
      rheumatoid arthritis (RA). METHODS: A total of 150 RA patients (102 female) were
      assessed for BMI and BF. Their habitual physical activity was assessed with the
      international physical activity questionnaire (IPAQ) and their energy intake with
      a 3-day food diary. Pro-inflammatory cytokines (interleukins, IL-1 and IL-6, and
      tumor necrosis factor-alpha), erythrocyte sedimentation rate, C-reactive protein,
      disease activity score-28 and physical function (Health Assessment Questionnaire
      HAQ) were also measured. RESULTS: BMI correlated inversely with IPAQ (r=-0.511,
      P=0.000) and positively with energy intake (r=0.331, P=0.016) and HAQ (r=0.133,
      P=0.042). BF correlated inversely with IPAQ (r=-0.575, P=0.000) and positively
      with HAQ (r=0.201, P=0.037). Normal weight patients were more physically active
      compared with those who were either overweight (P=0.006) or obese (P=0.000).
      Underweight patients consumed significantly fewer calories compared with other
      patients (P<0.05 in all cases). Cytokines or HAQ did not differ between weight
      groups. IPAQ was the sole predictor of obesity, whereas energy intake was the
      sole predictor of underweight. CONCLUSIONS: Inflammation does not seem to
      influence BMI and BF in RA. As in the general population, high levels of habitual
      physical activity associate with low BMI and BF in RA. Energy intake is a major
      determinant of being underweight in those who consume fewer calories. Further
      research is needed to investigate the suitability of exercise and diet
      modalities, and their effects on the body composition of RA patients.

PMID- 19859074
TI  - Testosterone deficiency, insulin resistance and the metabolic syndrome.
AB  - Changing lifestyles and an excess of food supply in developed countries have
      resulted in an increasing prevalence of overweight and obesity. As a consequence,
      a disorder of complex pathophysiology involving visceral adipose tissue as an
      endocrine organ, dyslipidemia, insulin resistance and hypertension has emerged
      the so-called metabolic syndrome. This disorder can lead to the manifestation of
      type 2 diabetes mellitus and cardiovascular disease. In men, testosterone
      deficiency may contribute to the development of the metabolic syndrome. In turn,
      states of hyperinsulinemia and obesity lead to a reduction of testicular
      testosterone production. Testosterone has reciprocal effects on the generation of
      muscle and visceral adipose tissue by influencing the commitment of pluripotent
      stem cells and by inhibiting the development of preadipocytes. Insulin
      sensitivity of muscle cells is increased by augmenting mitochondrial capacity and
      fostering expression of oxidative phosphorylation genes. Testosterone has a
      protective effect on pancreatic beta cells, which is possibly exerted by androgen
      receptor-mediated mechanisms and influence of inflammatory cytokines. As some,
      but not all, epidemiological and interventional studies indicate, testosterone
      substitution might be helpful in preventing or attenuating the metabolic syndrome
      in aging men with late-onset hypogonadism and in hypogonadal patients with type 2
      diabetes mellitus, but larger controlled trials are needed to confirm such
      hypotheses.

PMID- 19859076
TI  - Predictors of the early impairment of renal disease in human obesity.
AB  - OBJECTIVE: The mechanisms underlying the association of the increased albumin
      excretion rate (AER) with adiposity have yet to be clarified. We therefore
      investigated (1) the predictors of AER after 3 months of lifestyle intervention
      in a large cohort of nondiabetic obese women and (2) the relationships between
      AER and the adipose tissue gene expression of adipokines linked to inflammation
      and insulin resistance. SUBJECTS: A total of 269 obese nondiabetic women (age
      49.9+/-13.1 years, body mass index (BMI) 36.8+/-4.6 kg m(-2)) participated in
      this program. Measurements used were anthropometrics parameters, blood pressure,
      oral glucose tolerance test, lipids, creatinine, AER, homeostasis model
      assessment of insulin resistance (HOMA-IR) and glomerular filtration rate at
      baseline and after 3 months of lifestyle intervention. At baseline, in a subgroup
      of 34 women, subcutaneous adipose tissue biopsy was carried out for the analysis
      of mRNA expression levels of adiponectin, suppressor of cytokine signaling 3
      (SOCS-3), tumor necrosis factor alpha (TNF-alpha), pentraxine 3 (PTX-3),
      angiotensinogen and angiotensin-converting enzyme, and a blood sample was also
      taken from this group for the measurement of circulating adiponectin, interleukin
      6, TNF-alpha and PTX-3. Microalbuminuria was defined as albumin/creatinine ratio
      >or=3.5 mg mmol(-1). Real-time PCR was used to quantify mRNA. RESULTS: Six
      percent of obese women had microalbuminuria. When dividing the whole cohort into
      three groups according to AER changes (decrease, stability and increase), we
      noted that 2 h glucose, insulin and HOMA-IR significantly decreased (P<0.05 for
      all) only in women who had a decrease in AER, whereas BMI and waist circumference
      significantly decreased in all the three groups (P<0.05). At baseline, higher AER
      was associated to significantly higher adipose tissue mRNA expression levels of
      SOCS-3 and PTX-3 (P<0.05) and to higher TNF-alpha and angiotensinogen expression.
      CONCLUSIONS: In obese women, weight loss alone is not sufficient to induce the
      AER decrease that occurs only with a concomitant improvement in glucose
      homeostasis. The adipose tissue gene expression profile seems to favor the early
      renal impairment often seen in obese subjects.

PMID- 19859077
TI  - Indirect lifestyle intervention through wives improves metabolic syndrome
      components in men.
AB  - OBJECTIVES: It is well known that body weight loss through a direct (supervised)
      lifestyle intervention (LSI) improves obesity-related metabolic disorders. The
      purpose of this study was to investigate the effects of an indirect LSI on weight
      loss and metabolic syndrome (MetS) in spouses of LSI participants. METHODS: A
      total of 104 men (abdominal circumference > or = 85 cm; age, 52.1 + or - 9.3
      years) were assigned to one of three groups: no intervention (NI, n = 34), direct
      intervention (DI, n = 34) or indirect intervention (II, n = 36), the last of
      which consisted of subjects who did not participate in the direct LSI but whose
      wives did. Body weight and MetS components were measured before and after a 14
      week intervention. Daily energy intake and activity-related energy expenditure
      were assessed before and during the intervention. The LSI program was mainly
      consisted of dietary modifications with a physical activity program. RESULTS: No
      differences were observed across the three groups in any of the measures at
      baseline. Significant differences were observed among the groups in weight loss
      (NI, -0.7 + or - 1.4; DI, -6.2 + or - 3.3 and II, -4.4 + or - 3.7 kg) during the
      intervention. Along with the body weight reductions, significant improvements
      were observed in most of MetS components within the DI and II groups. When
      analyzing the spouse pairs in group II, significant correlations were observed in
      weight loss (r = 0.57) and decreased total energy intake (r = 0.54) between wives
      and husbands. CONCLUSIONS: Indirect LSI in abdominally obese men whose wives were
      undergoing LSI led to loss of weight and a decreased incidence of MetS,
      suggesting that indirect LSI may be an effective program for eliciting beneficial
      change in health status.

PMID- 19859078
TI  - Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in
      vitro adipocyte differentiation and in vivo obesity related to diabetes.
AB  - OBJECTIVE: Evodiamine (evo) has been shown to exert anti-inflammatory,
      antinociceptive and anticancer effects. In this study, we investigated the
      effects of evo alone and in combination with rosiglitazone (rosi) on in vitro
      adipocyte differentiation and in vivo obesity related to diabetes. METHODS:
      Adipocyte differentiation was investigated in vitro using 3T3-L1 and C3H10T1/2
      cells. To determine the degree of differentiation, Oil Red O staining and reverse
      transcription-PCR were carried out. Four groups of db/db mice were treated
      intraperitoneally once per day with vehicle, evo, rosi and evo+rosi. The mice
      were killed after 14 days and the blood, liver and adipose tissue were analyzed.
      RESULTS: The presence of evo or evo combined with rosi during adipogenic
      induction has been shown to inhibit adipocyte differentiation to a significant
      degree, particularly at the commitment and early induction stages. The evo and
      evo+rosi groups of db/db mice evidenced significant reductions in body weight
      gain. The ratio of epididymal white adipocyte tissue weight to body weight of the
      evo group was also significantly reduced. It is important to note that in the
      evo+rosi treatment, blood glucose levels were reduced to a degree similar to that
      of the rosi group, and plasma insulin levels were reduced significantly better
      than that of rosi group. Furthermore, hepatic lesions associated with fat and
      glycogen deposition were morphologically improved in the evo and evo+rosi groups.
      CONCLUSION: The results of this study showed that evo exerts an inhibitory effect
      on in vitro adipocyte differentiation and in vivo obesity, and also an
      improvement effect on insulin resistance. These desirable effects of evo were
      noted even in the presence of rosi. These results indicate that evo improves the
      undesirable effects of rosi, including adipogenesis, body weight gain and
      hepatotoxicity, while preserving its desirable blood-glucose-lowering effect.

PMID- 19859079
TI  - Effect of graded water immersion on vital capacity and plasma volume in patients
      with cervical spinal cord injury.
AB  - STUDY DESIGN: A case-control study was conducted. OBJECTIVE: The aim of the study
      was to test the hypothesis that the increase in hydrostatic pressure on the
      abdominal wall may be the major determinant of vital capacity (VC) improvement in
      tetraplegic subjects during water immersion, despite the blood volume shifts from
      the legs and abdomen to the thorax. SETTING: The study was carried out in the
      Rehabilitation Center, Brasilia/DF, Brazil. METHODS: In total, 11 men with
      tetraplegia (complete motor lesion, C4-7, 30.4 years old) and 12 healthy controls
      were studied. Hematocrit level and spirometry values were obtained on dry land
      and at each level of immersion (the pelvis, xiphoid and neck). RESULTS: Baseline
      spirometry value of tetraplegic subjects showed reduced VC (53.3+/-17.4% of
      predicted), whereas all control subjects had >80% of predicted values. Neither
      group showed significant changes in VC at the pelvic and xiphoid levels of
      immersion. In tetraplegic subjects, VC increased by 27.2% at the neck level (+/
      25.8, P<0.008), whereas in healthy subjects it decreased by 6.3% (+/-5.0,
      P<0.008). Both groups showed significantly increased inspiratory capacity only
      when immersed to the neck. Hematocrit level of tetraplegic subjects fell
      significantly with immersion to the xiphoid and neck levels (P<0.017), which
      occurred in controls only at the xiphoid level (P<0.017). CONCLUSIONS:
      Hydrostatic compression may be the main contributor to improving VC in
      tetraplegic subjects immersed in water. This improvement occurs despite increased
      plasma volume during immersion.

PMID- 19859080
TI  - Effects of dynamic sitting interventions on tissue oxygenation in individuals
      with spinal cord disorders.
AB  - STUDY DESIGN: An explorative cross-sectional study. OBJECTIVES: The objective of
      this study was to investigate the possibility of imposing dynamic sitting
      behavior on individuals with spinal cord disorders by using the Dynasit chair and
      to investigate its effect on the (sub-)cutaneous tissue oxygenation. SETTING:
      Rehabilitation Centre het Roessingh, Enschede, the Netherlands. SUBJECTS: Ten
      male subjects with a spinal cord disorder. METHODS: The Dynasit chair, an
      experimental simulator chair, containing mechanical concepts for postural
      adjustments, regulation of tuberal load and pelvic rotation, was developed to
      allow individuals with a spinal cord disorder to sit in a dynamic way. An
      experiment was carried out in which a dynamic sitting pattern was imposed. The
      sitting pattern consisted of series of actuated changes in posture, tuberal load
      and pelvic orientation. Effects of these changes on (sub-)cutaneous buttock
      tissue oxygenation were investigated by transcutaneous measurement of tissue
      oxygenation. RESULTS: Nonparametric statistical analyses were carried out on nine
      subjects that completed the study. Results showed significant positive effects
      (P<0.05) of actuated changes in tuberal load on the cutaneous and subcutaneous
      tissue oxygenation. CONCLUSION: The Dynasit chair is effective in imposing
      dynamic sitting behavior in individuals with a spinal cord disorder and
      consequently might reduce the chance of tissue degradation.

PMID- 19859081
TI  - The gamma-irradiated influenza vaccine and the prospect of producing safe
      vaccines in general.

PMID- 19859083
TI  - Nef, macrophages and B cells: a highway for evasion.

PMID- 19859082
TI  - Predicting CD62L expression during the CD8+ T-cell response in vivo.
AB  - Acute infection leads to CD8(+) T-cell activation, division and differentiation.
      Following clearance of infection, cells revert to two distinct subsets of memory,
      central (T(CM)) and effector (T(EM)) memory. Adoptive transfer of naive T-cell
      receptor transgenic (TCR-tg) T cells has been used to study the differentiation
      of these memory subsets, which are often discriminated by expression of CD62L.
      Naive CD8(+) T cells are CD62L(high), and CD62L expression is lost during the
      'effector' phase. Adoptive transfer studies show that higher transfer frequencies
      result in diminished T-cell expansion and a higher proportion CD62L(high). This
      suggests a relationship between CD62L expression and cell division, where
      division leads to conversion from CD62L(high) to CD62L(low) phenotype. To address
      this hypothesis we adoptively transferred graded numbers of OT-1 TCR-tg T cells
      from naive donors and tracked the kinetics and phenotype of the immune response
      after infection. We developed a simple mathematical model of division-linked
      CD62L differentiation, which we compared with the experimental data. Our results
      show that division-linked differentiation predicts the differences in proportion
      of cells CD62L(high) observed between responses of different adoptive transfer
      number and within individual mice. We calculate that approximately 20% of
      CD62L(high) cells convert to CD62L(low) during each division.

PMID- 19859084
TI  - Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell
      lung cancer treated with irinotecan-based chemotherapy.
AB  - Irinotecan induces small ubiquitin-like modifier (SUMO)-1 conjugation to
      topoisomerase-I, leading to enhanced sensitivity to irinotecan. In this study, we
      genotyped SUMO1 and UBC9 polymorphisms in 147 non-small-cell lung cancer (NSCLC)
      treated with irinotecan chemotherapy to investigate the association between
      genotypes and tumor response rate. Immunohistochemistry for SUMO1 and UBC9 was
      performed in 42 tumor samples and correlated with genotypes. The UBC9 10920CG
      genotype was associated with significantly higher response rate than the C/C
      genotype (81 vs 37%, P=0.0002). This predictive effect on tumor response was also
      seen in multivariate analysis (odds ratio=8.5, P=0.003). Moreover, tumors arising
      from the UBC9 10920CG genotype were associated with higher prevalence of SUMO1
      overexpression compared with those with CC genotype (78 vs 31%, P=0.021). This
      finding suggests that the UBC9 10920CG genotype enhances sensitivity to
      irinotecan chemotherapy in advanced NSCLC through upregulation of SUMO1 in tumor
      cells.

PMID- 19859086
TI  - Climate change: the health consequences of inactivity.

PMID- 19859085
TI  - Endocytosis of FcalphaR is clathrin and dynamin dependent, but its cytoplasmic
      domain is not required.
AB  - FcalphaR, the Fc receptor for IgA, is essential for IgA-mediated immune
      responses. Previous studies have shown that IgA and IgA immune complexes can be
      rapidly endocytosed by FcalphaR. However, the underlying mechanism remains
      unclear. Here, we investigated the endocytic pathway of FcalphaR in monocytic
      cell line, U937, that naturally express FcalphaR and in transfected Chinese
      hamster ovary (CHO), COS-7 and Hela cells. By using selective chemical inhibitors
      of different endocytic pathways, overexpression of dominant-negative mutants of
      Eps15 and knockdown of clathrin heavy chain (CHC) via RNA interference, we
      demonstrated that endocytosis of FcalphaR was through a clathrin-mediated
      pathway. The endocytosed FcalphaR went into Rab5- and Rab11-positive endosomes.
      However, endocytosis of FcalphaR could not be blocked by a dominant-negative
      mutant of Rab5. We also demonstrated that endocytosis of FcalphaR was dynamin
      dependent by overexpressing a dominant-negative mutant of dynamin. The potential
      endocytic motif for FcalphaR was also examined. Unexpectedly, we found that the
      entire cytoplasmic domain of FcalphaR was not required for the endocytic process
      of FcalphaR. We conclude that endocytosis of FcalphaR is clathrin- and dynamin
      dependent, but is not regulated by Rab5, and the endocytic motif is not located
      in the cytoplasmic domain of FcalphaR.

PMID- 19859087
TI  - Where has carotid stenting gone?

PMID- 19859088
TI  - Teaching and learning in the hospital ward.
AB  - AIM: To explore ways in which student learning during formal ward rounds can be
      enhanced. METHOD: Qualitative study of University of Otago medical students
      (Dunedin, New Zealand) involving observation of surgical teams during formal ward
      rounds, and indepth interviews with students and consultant surgeons. RESULTS:
      Teaching and learning opportunities on ward rounds were often missed by both
      clinical teachers and students as service provision and patient care took
      precedence. As a result, students often felt excluded and frequently expressed
      ambivalence about the educational value of formal whole team ward rounds.
      Students were more likely to consider themselves part of the team when they felt
      useful and were included in team discussions about patient care. They reported
      that they learned more effectively on smaller, more educationally focussed ward
      rounds that incorporated bedside tutorials and opportunities to practice
      examination skills. CONCLUSION: Students and clinical teachers know that students
      need to make the most of learning opportunities by being proactive, spending time
      on the ward, being useful, asking questions. Clinical staff can facilitate
      student learning by consciously including students in the business of patient
      care. This means inviting students to ask questions and examine wounds,
      physically guiding hands on examinations, encouraging students to pay attention
      to discussions among the clinical team, and explaining what is being discussed.

PMID- 19859089
TI  - The training, experience, and confidence of junior doctors in performing pleural
      procedures.
AB  - AIM: Pleural procedures may cause patient discomfort and serious complications if
      performed inadequately. We surveyed junior doctors to provide information about
      training and experience. METHODS: We surveyed 493 junior doctors working in
      departments involved in pleural procedures in three teaching hospitals via postal
      questionnaires in 2002. RESULTS: The response rate was 66%. Formal training in
      the performance of pleural procedures was limited at undergraduate and
      postgraduate levels. Theoretical training at postgraduate level in pleural
      aspiration, chest drain insertion, and closed pleural biopsies was reported by
      34%, 40%, and 14% of respondents respectively. Practical training using animal or
      artificial models occurred infrequently. Pleural aspiration, chest drain
      insertion, and pleural biopsy had been performed at least once by 91%, 66%, and
      41% of respondents respectively. Most doctors felt they needed more training in
      chest drain insertion and pleural biopsy. Confidence in performing procedures was
      related to the number of times the procedure had been performed but not to formal
      teaching. CONCLUSIONS: This study provides a comprehensive survey of the
      background training, experience and confidence levels of junior medical staff in
      performing pleural procedures. Training in pleural procedures was limited and our
      results suggest the need for better training programmes and supervision of junior
      doctors.

PMID- 19859090
TI  - Human papillomavirus knowledge and awareness among undergraduates in healthcare
      training in New Zealand.
AB  - AIMS: To describe knowledge of HPV and its transmission, knowledge of the HPV
      vaccine, and awareness of free HPV vaccine for 12-18 year old New Zealand
      females; and to assess whether there are significant age and gender differences
      in HPV-related knowledge. METHODS: Undergraduate university students were invited
      to complete an anonymous questionnaire, after viewing a brief HPV vaccine TV
      commercial. RESULTS: Compared to 19 year olds, 18 years olds were more likely to
      have heard of HPV (OR=3.78; 95%CI=1.66-8.65) and the HPV vaccine (OR=3.94;
      95%CI=1.85-8.39), know about sexual transmission of HPV (OR=2.79; 95%CI=1.34
      5.77), and be aware of the free HPV vaccine (OR=4.00; 95%CI=1.81-8.84).
      Participants who knew someone ever diagnosed with cervical cancer were more
      likely to have heard of the HPV vaccine (OR=2.98; 95%CI=1.09-8.13). Male
      participants were less likely to be aware of the free vaccine (OR=0.16;
      95%CI=0.07-0.40). CONCLUSION: Average levels of basic knowledge of HPV and HPV
      vaccine most likely represent minimal awareness as more specific knowledge on
      sexual transmission of HPV is low. HPV vaccination should be complimented with
      public education on the link between sexual behaviour, HPV infection and cervical
      cancer.

PMID- 19859091
TI  - Customised molecular diagnosis of primary immune deficiency disorders in New
      Zealand: an efficient strategy for a small developed country.
AB  - INTRODUCTION: Primary Immune Deficiency disorders (PIDs) are uncommon conditions,
      which necessitate urgent diagnosis in order to prevent disabling complications
      such as bronchiectasis. Timely diagnosis can be life-saving in children with PIDs
      such as severe combined immune deficiency. METHODS: A customised molecular
      diagnostic service was established in New Zealand in 2005. Most patients referred
      to the service have undergone genetic counselling before blood was drawn for
      testing. Genomic DNA was extracted and polymerase chain reaction (PCR) performed
      to amplify genes of interest, followed by DNA sequencing. The DNA sequences were
      then aligned with wild type sequence using computer software to identify possible
      mutations. RESULTS: Mutational analysis was undertaken in 27 probands with
      suspected PID. Seven causative mutations were identified in these patients.
      Family studies have been undertaken after genetic counselling. CONCLUSIONS:
      Customised genetic testing is a cost-effective and efficient method for PID
      diagnosis in a small developed country.

PMID- 19859092
TI  - Outcome and prognostic factors on 57 cases of infective endocarditis in a single
      centre.
AB  - AIM: We aim to evaluate the clinical characteristics and outcome of infective
      endocarditis in our hospital, and the prognostic significance of recurrent
      endocarditis. METHODS: A single centre retrospective review of all cases of
      infective endocarditis (IE) was undertaken for a 5-year period from June 2002.
      RESULTS: There were 57 episodes of IE in 47 patients. Seventy percent were
      definite IE using the modified Duke Criteria (2000). The most commonly isolated
      organisms were Streptococci (37%) and Staphylococcus aureus (35%). Forty-nine
      percent of patients remained event-free from death, recurrence, or operation at
      the end of follow-up period. Five cases (8.5%) had early recurrence of
      endocarditis within 60 days. Eleven patients (23%) died during follow-up (mean 14
      months). There was no significant increase in mortality of patients with history
      of recurrent endocarditis (38% vs 28%; p=0.39). Staphylococcus aureus was
      associated with increased mortality or need for valve surgery (OR 4.5; 95%CI 1.38
      14.8), risk of neurological events (OR 8.9; 1.5-52), renal failure (OR 7.2; 1.7
      30) and thrombocytopenia (OR 5.6; 1.4-22). CONCLUSIONS: The mortality of IE
      remains high. Less than half of this cohort remained event-free. The micro
      organism involved is more predictive of mortality or need for surgery than
      recurrent endocarditis.

PMID- 19859093
TI  - Utilisation of inpatient cardiology services including by Maori: a study of
      hospital discharges for patients enrolled with Partnership Health practices for
      the 2 years ending June 2007.
AB  - AIMS: Some previous studies have shown that Maori utilise cardiology inpatient
      services at a much lower rate than would be expected by their health status and
      mortality. Using more recent data, this study seeks to determine whether this is
      still the case by examining Maori rates of utilisation of cardiology inpatient
      services. METHODS: Practice enrolment data for 354,383 patients, including age,
      gender, ethnicity (19,712 Maori), deprivation score (patient domicile) and other
      variables were sent by the Partnership Health Primary Health Organisation (PHO)
      to NZHIS. Discharge data for 127,426 patients for the 2 years ending June 2007
      were attached to the enrolment data. These were analysed for rates of utilisation
      including cardiology in patient services by diagnosis related groups (DRGs).
      Maori rates were standardised to the age mix of the total population. RESULTS:
      Standardised Maori rates of utilisation for almost all major cardiology diagnosis
      related groups (DRG) categories were substantially higher than the non-Maaori
      population. Overall rates for cardiology DRGs were 1.47 times higher for Maori.
      Standardised Maori rates were higher than the non-Maori population for higher
      deprivation scores. Maori cardiology inpatients had almost twice the level of
      Care Plus levels than the non-Maori population. CONCLUSION: The findings indicate
      that Maori have much better access to cardiology inpatient services than shown in
      some previous studies. They therefore appear to be benefiting from such services.
      However the higher rate of hospital utilisation suggests that improved data
      rather than increased access is the explanation, It raises questions as to
      whether the additional Care Plus funding being received is having the desired
      outcomes. Further perhaps targeted action is needed at the primary care level to
      improve both access to and utilisation of such services.

PMID- 19859094
TI  - Why New Zealand must rapidly halve its greenhouse gas emissions.
AB  - New Zealand must commit to substantial decreases in its greenhouse gas emissions,
      to avoid the worst impacts of climate change on human health, both here and
      internationally. We have the fourth highest per capita greenhouse gas emissions
      in the developed world. Based on the need to limit warming to 2 degrees C by
      2100, our cumulative emissions, and our capability to mitigate, New Zealand
      should at least halve its greenhouse gas emissions by 2020 (i.e. a target of at
      least 40% less than 1990 levels). This target has a strong scientific basis, and
      if anything may be too lenient; reducing the risk of catastrophic climate change
      may require deeper cuts. Short-term economic costs of mitigation have been widely
      overstated in public debate. They must also be balanced by the far greater costs
      caused by inertia and the substantial health and social benefits that can be
      achieved by a low emissions society. Large emissions reductions are achievable if
      we mobilise New Zealand society and let technology follow the signal of a
      responsible target.

PMID- 19859095
TI  - The power of apology.
AB  - In the aftermath of an adverse event, an apology can bring comfort to the
      patient, forgiveness to the health practitioner, and help restore trust to their
      relationship. According to the Health and Disability Commissioner: "The way a
      practitioner handles the situation at the outset can influence a patient's
      decision about what further action to take, and an appropriate apology may
      prevent the problem escalating into a complaint to HDC". Yet, for many health
      practitioners saying "I'm sorry" remains a difficult and uncomfortable thing to
      do. We can help to bring down this wall of silence by developing a clear
      understanding of the importance of apologies to patients and health
      practitioners; appreciating the difference between expressing empathy and
      accepting legal responsibility for an adverse outcome; knowing the key elements
      of a full apology and when they should be used; and supporting those who have the
      honesty and courage to say "I'm sorry" to patients who have been harmed while
      receiving healthcare.

PMID- 19859096
TI  - Swine H1N1 influenza in a post liver transplant patient.

PMID- 19859097
TI  - Medical image. Combined surgery and repeated angioembolisation for a post
      pancreatitis pseudoaneurysm.

PMID- 19859098
TI  - Medical image. A case of lumbodynia.

PMID- 19859099
TI  - A design fault in New Zealand's health research funding system exposed by
      pandemic influenza.

PMID- 19859100
TI  - Comprehensive strategy towards delivering better communications and better health
      care to non-English speaking New Zealanders?

PMID- 19859101
TI  - Tumbu and botflies: an underestimated nuisance for travellers in Africa and South
      America?

PMID- 19859102
TI  - Vaccinations (or lack of them) for student doctors.

PMID- 19859103
TI  - Go and see.

PMID- 19859105
TI  - Backscatter signatures of knots.
AB  - We examine the knottedness of a structure through optical or electromagnetic wave
      scattering as a first step in the investigation of scattering from and
      propagation through knotted media. Initial investigations demonstrate that the
      handedness of knots and the degree of knottedness can be deduced from the
      backscatter signature for the examples considered.

PMID- 19859106
TI  - Fresnel diffraction of substructured gratings: matrix description.
AB  - We present a matrix formalism to describe the near-field diffraction pattern, at
      fractions of a Talbot distance, of a grating whose unit cell is composed of a
      discrete substructure. We show that this formalism is useful for designing
      Lohmann array illuminators.

PMID- 19859107
TI  - Diffractive phase elements based on two-dimensional artificial dielectrics.
AB  - We have designed, fabricated, and tested a blazed artificial dielectric
      transmission grating in fused quartz for use at the 633-nm wavelength. By locally
      varying the index, using fabricated two-dimensional arrays of dielectric
      cylinders, we can achieve a desired phase modulation to produce a diffractive
      phase element in one processing step. The effective index depends on the fill
      fraction of the cylinders.

PMID- 19859108
TI  - Parametric characterization of coherent, lowest-order Gaussian beams propagating
      through hard-edged apertures.
AB  - Analytical expressions for the width, far-field divergence, crossed moment, and
      generalized beam-quality parameter of a coherent, lowest-order Gaussian beam
      propagating through hard-edged slits are given in terms of the size of the
      opening and of the position of the aperture plane with respect to the beam waist.
      Some optimization criteria of these beam-shape parameters are also inferred.

PMID- 19859109
TI  - Pump depletion through coherent energy transfer in semiconductors.
AB  - Experimental and theoretical study of multiwave mixing in semiconductors shows
      that a pump beam may be depleted through coherent energy transfer by a probe with
      either positive or negative pump/probe detuning. The gain modification is a sum
      of symmetric and antisymmetric parts associated with on-resonant and off-resonant
      effects, respectively. The intracavity probe power required for a given pump
      depletion is linearly dependent on detuning. Laser mode depletion causes mode
      switching that gives polarization and frequency conversion with high signal gain
      and high contrast.

PMID- 19859110
TI  - Observation of stimulated orientational scattering and cross-polarized self
      starting phase conjugation in a nematic liquid-crystal film.
AB  - We have observed stimulated extraordinary-ordinary wave scattering and cross
      polarized self-starting optical phase conjugation effects in a nematic liquid
      crystal film. The basic mechanism involved is the nonresonant laser-induced
      nematic crystal axis reorientation. These processes require low optical power and
      are characterized by millisecond response speed.

PMID- 19859111
TI  - Dark optical bullets in light self-trapping.
AB  - Dark optical bullets-the stationary states of pulsed (3 + 1)-dimensional dark
      self-trapped beams propagating in uniform self-defocusing Kerr-law media without
      change in space and time-are found possible in the anomalous dispersion region,
      and the states are shown to be stable. This contrasts with the corresponding
      light bullets in self-focusing media that collapse in Kerr-law nonlinearity. On
      the other hand, in the normal dispersion region the pulsed dark self-trapped
      beams break as a result of the combined effects of diffraction, dispersion, and
      nonlinearity.

PMID- 19859112
TI  - Multisoliton interactions and wavelength-division multiplexing.
AB  - Multisoliton interactions are studied with an asymptotic expansion of the N
      soliton solution in the limit of large frequency separation between the channels.
      In this limit the spectral distortion is small and the peak frequency shift of a
      channel is the sum of pairwise shifts as a result of interaction with other
      channels. These results, derived for collisions among an arbitrary number of
      channels, will be useful in estimating the limits on the minimum channel spacings
      and packet sizes for a wavelength-multiplexed optical communication system.

PMID- 19859113
TI  - Finite-element analysis of hybrid modes in uniaxial planar waveguides by a simple
      iterative method.
AB  - An efficient computer-aided solution procedure based on the finite-element method
      is developed for the analysis of hybrid waves guided by uniaxial planar
      waveguides for the case when the optical axis is in the plane of the slab. In
      this approach, self-consistent solutions are obtained by a simple iterative
      scheme. Dispersion relations for hybrid waves in a multimode uniaxial planar
      waveguide are given and compared with analytical results.

PMID- 19859114
TI  - Electro-optic and thermo-optic measurements of birefringence of LiNbO(3)
      waveguides.
AB  - We measure the birefringence Deltabeta = beta- beta TE of LiNbO(3):Ti single-mode
      strip waveguides at lambda = 1.54 microm by scanning a polarization-coupling
      perturbation along the guide and observing the variations of output polarization.
      With electro-optic and thermo-optic probing, beat lengths of 20 microm to 20 mu;m
      are measured with a resolution of up to delta(Deltabeta) approximately 10(-3) cm(
      1).Influences of temperature and strip width on Deltabeta are observed.

PMID- 19859115
TI  - Kilohertz allsolid-state picosecond lithium triborate optical parametric
      generator.
AB  - An all-solid-state picosecond optical parametric generation system that uses a
      single-pass noncritically phase-matched lithium triborate crystal is
      demonstrated. We have achieved > 20% total conversion from lambda = 532 nm (pump)
      to lambda = 800 nm (signal) and 1.6 microm (idler) with a pulse width of ~15 ps
      and average power of 200 mW at a repetition rate of 3 kHz (~50 microJ/signal
      pulse). Frequency tuning from <750 nm to >1.8 microm is achieved by temperature
      tuning of the lithium triborate.

PMID- 19859116
TI  - Efficient operation of a room-temperature Nd:YAG 946-nm laser pumped with
      multiple diode arrays.
AB  - Efficient pulsed room-temperature laser operation at 946 nm is reported for
      Nd:YAG pumped with multiple diode array bars. We achieved high pump brightness by
      collimating the outputs from individual bars and focusing them onto the end of a
      short 3-mm-diameter rod. An average power of 470 mW at 100 Hz was obtained with
      an optical slope efficiency of 15% based on incident pump power, and greater than
      1 W of output was obtained at 300 Hz. Intracavity frequency doubling with KNbO(3)
      resulted in 40-70-mW output at 473 nm. Q-switched operation is also reported.

PMID- 19859117
TI  - Noncollinear parametric generation in LiIO(3) and beta-barium borate by frequency
      doubled femtosecond Ti:sapphire laser pulses.
AB  - In LiIO(3) and BBO crystals the wave-matching conditions for femtosecond
      noncollinear parametric light generation at lambda = 390 nm pumping wavelength
      are investigated. In the LiIO(3) crystal simultaneous phase- and group-velocity
      matching angles are determined. Parametric generation occurred at 0.45-2.9-mu;m
      wavelengths by pumping with the second harmonic of 150-fs Ti:sapphire laser
      pulses and is in qualitative agreement with calculated directions in both
      crystals.

PMID- 19859118
TI  - High-power longitudinally end-diode-pumped Nd:YLF regenerative amplifier.
AB  - We describe a high-power compact diode-pumped Nd:YLF regenerative amplifier. The
      pumping source is a 15-W diode-laser array that is focused into the laser crystal
      with a longitudinal end-pumping arrangement based on an array of cylindrical
      microlenses. Seeded with 15-ps pulses from a diode-pumped and mode-locked Nd:YLF
      oscillator, the regenerative amplifier produces pulses of 0.5-mJ energy at a 1
      kHz repetition rate. A pulse energy as high as 0.75 mJ is achieved at a 500-Hz
      repetition rate and below.

PMID- 19859119
TI  - High-efficiency TEM(00) Nd:YVO(4) laser longitudinally pumped by a high-power
      array.
AB  - A new simple, compact, and efficient optical device is presented that allows any
      commercially available arrays or stacks to longitudinally pump laser materials. A
      Nd:YVO(4) laser was built and an optical-optical efficiency as great as 50% was
      demonstrated with a diffraction-limited beam.

PMID- 19859120
TI  - Argon-ion-pumped and diode-pumped all-solid-state femtosecond Cr:LiSrAlF(6)
      regenerative amplifiers.
AB  - A tunable femtosecond solid-state amplifier system that uses only 3 W of 488-nm
      argon-ion pump power has been demonstrated to deliver microjoule pulses at
      repetition rates up to 20 kHz, with a maximum pulse energy of 14 mu;J obtained at
      5 kHz. An all-solid-state, tunable, diode-pumped Cr:LiSrAlF(6) regenerative
      amplifier has been demonstrated, for the first time to our knowledge, that
      amplifies femtosecond pulses to energies exceeding 1 mu;mJ at up to a 16-kHz
      repetition rate.

PMID- 19859121
TI  - Starting dynamics of a cw passively mode-locked picosecond Ti:sapphire/DDI laser.
AB  - We show that, for a cw passively mode-locked picosecond Ti:sapphire/DDI laser,
      the first autocorrelation trace with negligible cw background occurs at a delay
      time of 20 mu;s, or 1600 round trips from the first relaxationoscillation peak.
      The trace suggests that the pulse consists of a primary pulse as short as 4.4 ps
      and of small secondary pulses that form a much wider pedestal of the trace, each
      containing approximately 50% of the photon energy. Nearly transform-limited
      approximately 5-ps-wide Gaussian pulses were observed at a delay time of 40 mu;s.
      After 45 mu;s, the optical spectrum broadened considerably, and the time
      bandwidth product increased to 4 in the steady state (after 60 micros).

PMID- 19859122
TI  - Picosecond Ti:sapphire-pumped optical parametric oscillator based on LiB(3)O(5).
AB  - We report a high-repetition-rate, singly resonant optical parametric oscillator
      based on the nonlinear crystal LiB(3)O(5), which is synchronously pumped by a
      continuous train of picosecond pulses from a self-mode-locked Ti:sapphire laser.
      Under temperature-tuned noncritical type I phase matching, total average near
      infrared output powers of 90 mW at a repetition rate of 81 MHz have been
      generated over a signal (idler) tuning range of 1.374-1.530 microm (1.676-1.828
      microm). Without dispersion compensation, transform-limited signal pulses with
      durations of 520-780 fs have been obtained at 1.2 times threshold for 1.8-ps
      input pump pulses.

PMID- 19859123
TI  - High-energy, high-efficiency harmonic generation from a Cr:LiSrAlF(6) laser
      system.
AB  - We have developed a near-diffraction-limited Q-switched Cr:LiSrAlF(6) (Cr:LiSAF)
      laser system capable of producing 860-nm, 400-mJ pulses at a repetition rate of 2
      Hz. Our harmonic-generation experiments with beta-BaB(2)O(4) nonlinear crystals
      have yielded 200 mJ of energy at 430 nm and 40 mJ at 215 nm. To the best of our
      knowledge, the 50% second-harmonic conversion efficiency and UV energy
      demonstrated in this research are the highest yet obtained from a Cr:LiSAF laser.

PMID- 19859124
TI  - High-power soliton fiber laser based on pulse width control with chirped fiber
      Bragg gratings.
AB  - Chirped fiber Bragg gratings control the pulse width and energy in Kerr mode
      locked erbium fiber soliton lasers. We create high-energy pulses by providing
      large amounts of excessive negative dispersion, which increases the pulse width
      while keeping the nonlinearity of the cavity constant. With a chirped fiber
      grating of 3.4-ps(2) dispersion, 3-ps pulses with an energy content higher than 1
      nJ are generated at a repetition rate of 27 MHz. By controlling the polarization
      state in the cavity, we obtain a tuning range from 1.550 to 1.562 mu;m.

PMID- 19859125
TI  - Transient photocurrents in photoconductive semiconductors generated by step-phase
      modulations.
AB  - Transient photocurrents generated in photoconductive semiconductors by two
      coherently interfering optical fields in two-wave mixing experiments were
      observed when the signal beam was phase modulated by a step signal. Expressions
      describing the behavior of the transient photocurrent were derived and verified
      experimentally. Such transient photocurrents are insensitive to the static
      carrier phase differences between the two optical fields and can be used to
      detect sudden phase variations between two interfering optical fields.

PMID- 19859126
TI  - Four-wavelength Bragg mirror using GaAs/AlAs.
AB  - We report on the design and growth by molecular beam epitaxy of a GaAs/AlAs Bragg
      mirror with four reflectivity bands. High reflectivity is achieved in all the
      bands, and there is good agreement between measured and simulated results.

PMID- 19859127
TI  - Dependence of output coupling efficiency on detuning in surface grating output
      couplers.
AB  - The dependence of output coupling efficiency on the periodicity of a surface
      grating outcoupler was investigated. Horizontal cavity InGaAs/AlGaAs laser
      oscillators with two first-order surface gratings as feedback elements were
      integrated with detuned rectangular second-order gratings as surface output
      couplers by the use of electron-beam lithography and chemically assisted ion-beam
      etching. A high surface emission efficiency of more than 60% was achieved for
      grating periodicities detuned -2.5 nm to -15 nm and +2.5 nm from the resonance
      periodicity of 295 nm. For larger positive detuning, the surface emission
      efficiency is reduced because of the onset of secondorder diffraction into the
      substrate.

PMID- 19859129
TI  - Forced TM-mode operation of a GaAlAs laser diode by use of annealed proton
      exchanged LiNbO(3) and LiTaO(3) waveguides.
AB  - Forced TM-mode operation of GaAlAs laser diode by use of annealed proton
      exchanged LiNbO(3) and LiTaO(3) waveguides as the polarizing element in an
      external cavity is demonstrated. The results are compared with those for an
      external cavity that uses a bulk polarizer. The dependence of such factors as the
      amount and polarization of the feedback in these external cavity configurations
      is discussed.

PMID- 19859128
TI  - Room-temperature amplitude-squeezed light from an injection-locked quantum-well
      laser with a time-varying drive current.
AB  - We demonstrate the conversion of a time-varying (50-400-MHz) electrical current
      into an optical power with fidelity 0.8 dB (1.35 dB after correction for
      detection efficiency) beyond the standard quantum limit by drive-current
      modulation of an injection-locked quantum-well laser.

PMID- 19859130
TI  - Femtosecond harmonically mode-locked fiber laser with time jitter below 1 ps.
AB  - We have made an experimental study of the time jitter in a harmonic passively
      mode-locked fiber soliton ring laser. We demonstrate that jitter as low as 600 fs
      (100-550 Hz), which is less than the soliton pulse width, can be achieved at a
      repetition frequency of 463 MHz. The results support the suggestion that the
      stability of the laser is dependent on the long-range soliton interaction through
      the excitation of acoustic waves that is induced by the propagating pulses.

PMID- 19859131
TI  - Phase control for production of high-fidelity optical pulses for chirped-pulse
      amplification.
AB  - We demonstrate continuous tuning of the cubic and quartic phases of the pulse
      stretcher in a chirped-pulse amplification laser system. We obtain near-bandwidth
      limited recompression of 100-fs pulses by minimizing the total phase through
      fourth order.

PMID- 19859132
TI  - Controllable dual-wavelength operation of a femtosecond neodymium fiber laser.
AB  - Simultaneous asynchronous mode locking of two wavelengths in a Nd(3+)-doped fiber
      laser is reported. The laser operates simultaneously at wavelengths of 1.060 and
      1.100 microm where carrier-type passive mode locking is employed for the shorter
      wavelength and Kerr-type passive mode locking is used for the longer wavelength.
      The difference between the two repetition rates may be varied over a range from
      several megahertz to 500 Hz, limited by the onset of pulse interactions at small
      difference frequencies.

PMID- 19859134
TI  - Optical logarithmic transformation of speckle images with bacteriorhodopsin
      films.
AB  - The application of logarithmic transformations to speckle images is sometimes
      desirable in converting the speckle noise distribution into an additive, constant
      variance noise distribution. The optical transmission properties of some
      bacteriorhodopsin films are well suited to implement such a transformation
      optically in a parallel fashion. I present experimental results of the optical
      conversion of a speckle image into a transformed image with signalindependent
      noise statistics, using the real-time photochromic properties of
      bacteriorhodopsin. The original and transformed noise statistics are confirmed by
      histogram analysis.

PMID- 19859133
TI  - Second-harmonic generation of amplified femtosecond Ti:sapphire laser pulses.
AB  - We study theoretically and experimentally second-harmonic generation (SHG) of 150
      fs-duration amplified Ti:sapphire laser pulses at a wavelength of 780 nm in the
      nonlinear crystal KDP of different lengths and at different power densities as
      high as 150 GW cm(-2). The experimentally observed SHG conversion efficiency does
      not exceed 50%. It is shown theoretically that one possible process limiting the
      SHG efficiency at low as well as at high intensities is the modulation of the
      phase of the fundamental wave. In addition, continuum generation is observed at
      high intensities and can decrease the SHG efficiency.

PMID- 19859135
TI  - Laser-induced collisional autoionization in europium and strontium atoms.
AB  - An experiment that involves laser-induced collisional autoionization in europium
      and strontium atoms is proposed and the spectral line shape of the cross section
      is calculated on the basis of data available in the literature. The feasibility
      of the experiment both in oven cells and in a crossed-atomic-beam geometry is
      discussed.

PMID- 19859136
TI  - Particle image velocimetry: direct pulsed image recording on a bistable optically
      addressed spatial light modulator for real-time fluid flow mapping.
AB  - We describe direct pulsed image recording onto a bistable optically addressed
      spatial light modulator in particle image velocimetry (PIV). By coupling this
      technique with the parallel optical spatial autocorrelator for PIV data
      processing, one can obtain a fluid flow map within seconds without the necessity
      for off-line processing. The feasibility of recording a double-pulsed particle
      image is explored and demonstrated experimentally.

PMID- 19859137
TI  - Heterodyne nondegenerate pump-probe measurement technique for guided-wave
      devices.
AB  - We describe a new heterodyne nondegenerate pump-probe waveguide measurement
      technique that permits independent control of wavelengths, pulse widths, and
      polarizations of the pump and probe pulses in a collinear geometry. This
      technique provides both time- and spectral-domain information and can be applied
      to transmission and index measurements alike. We demonstrate this technique for
      the measurement of gain dynamics in a strained-layer single-quantum-well diode
      laser.

PMID- 19859139
TI  - Measurement of a wind field with an airborne continuous-wave Doppler lidar.
AB  - An airborne homodyne conical scanning Doppler lidar for the measurement of a wind
      field has been built and was operated in a first test flight in May 1994. The
      design of the optic is described, and the single steps of the signal-processing
      chain to calculate an average wind are discussed. The results of a flight over
      Lake Ammersee are presented and are compared with the data obtained from the
      inertial reference system of the aircraft.

PMID- 19859138
TI  - Optical fiber interferometry for photoacoustic spectroscopy in liquids.
AB  - Optical fiber interferometry was used for measurement of the subnanometer surface
      and bulk displacements associated with photoacoustic pressure waves in methanol
      and water. The measurement system is both broadband and noncontacting, giving a
      pressure sensitivity of 0.1 Pa/ radicalHz.

PMID- 19859141
TI  - Stripe stacker for use with laser diode bars.
AB  - An optical device that reconfigures the output of a laser diode bar source to a
      more compact pointlike format is described. The design is an adaptation of image
      slicers used for many years in astronomical spectroscopy and has the advantages
      of simple construction and high efficiency.

PMID- 19859140
TI  - Spectral stability and smoothness of a phase-modulated fiber laser.
AB  - A fiber laser is phase modulated in the presence of a weak external reflection,
      leading to a strong intensity modulation at the laser output. The modulation
      causes the optical spectrum to be substantially more stable and smooth. The
      usefulness of the improved spectrum is illustrated by two different experiments,
      one for the characterization of an optical filter by measurement of its influence
      on the laser spectrum and the other for the measurement of the spatial-mode group
      delay difference in a two-mode fiber by use of white-light interferometry. In
      both experiments the noise level is substantially reduced when the phase
      modulated source is used.

PMID- 19859142
TI  - Photoanisotropic incoherent-to-coherent converter using a bacteriorhodopsin thin
      film.
AB  - We have fabricated a novel optically addressed spatial light modulator by using
      bacteriorhodopsin immobilized in a polymer thin film. This incoherent-to-coherent
      converter is based on photoinduced anisotropy, as distinguished from previously
      reported devices based on photochroism in bacteriorhodopsin. This system is
      capable of a resolution of 114 lines/mm with a contrast ratio of 100:1.

PMID- 19859143
TI  - Characteristics of crystallographic gratings.
AB  - We report the observation and characterization of a resonance effect in gratings
      fabricated on GaAs substrates by use of a crystallographically preferential wet
      chemical etch that terminates at the (111) family of planes. Also, we demonstrate
      an in situ etch-monitoring study of the diffraction characteristics of these
      gratings. The light intensity in the first order of diffraction was monitored in
      Littrow reflection during etching at 632.8- and 543.5-mm wavelengths. Scanning
      electron microscopy was performed on several samples to correlate the etch depth
      with diffraction efficiency. The variation of diffraction intensity with depth
      showed a narrow peak at a shallower grating depth and a broader peak at a larger
      grating depth. These diffraction characteristics are explained on the basis of a
      competitive interaction between the resonance effect of the incident optical mode
      and the magnitude of the first Fourier component of the grating profile that
      primarily couples the incident and diffracted optical modes.

PMID- 19859144
TI  - Imaging in diffuse media with ultrafast degenerate optical parametric
      amplification.
AB  - We demonstrate the application of a subpicosecond optical parametric amplifier
      working at degeneracy to imaging in diffuse media. This optical parametric
      amplifier exhibits small-signal gains greater than 10(4), thereby acting as a
      high-gain ultrafast amplifying gate. We have used it to construct the image of a
      grid pattern hidden behind 20 mean free paths of a highly diffusing solution of
      latex microspheres with a spatial resolution of 200 microm.

PMID- 19859145
TI  - Huygens-Fresnel principle in the near field.
AB  - The Huygens-Fresnel principle provides a conceptual understanding for wave
      propagation and diffraction. Recently the principle has been reexamined to
      suggest that it is also valid in the near field. We reformulate the problem in
      terms of nonradiative optics, focusing particularly on the obliquity factor
      inherent in the forward-directed propagation of light. In the near field of
      matter no explicit obliquity factor exists.

PMID- 19859146
TI  - Proposed method for molecular optical imaging.
AB  - We can resolve multiple discrete features within a focal region of m spatial
      dimensions by first isolating each on the basis of n >/= 1 unique optical
      characteristics and then measuring their relative spatial coordinates. The
      minimum acceptable separation between features depends on the point-spread
      function in the (m + n)d-dimensional space formed by the spatial coordinates and
      the optical parameters, whereas the absolute spatial resolution is determined by
      the accuracy to which the coordinates can be measured. Estimates of each suggest
      that near-field fluorescence excitation microscopy/spectroscopy with molecular
      sensitivity and spatial resolution is possible.

PMID- 19859147
TI  - Influence of diffraction on hard-aperture Kerr-lens mode locking.
AB  - It is demonstrated that with rigorous inclusion of diffraction on an intracavity
      hard aperture the values of the nonlinear differential loss coefficient Gamma
      (which characterizes the efficiency of Kerr-lens mode locking) are several times
      higher than in the commonly used simplified approach in which diffraction effects
      are neglected. Diffraction changes modal properties and causes a faster decrease
      of mode losses with increasing power than predicted by the traditional approach.
      With this correction, the discrepancy between the Kerr-lens mode-locking theory
      and the theoretical estimates of the self-starting condition is substantially
      decreased.

PMID- 19859148
TI  - Multiphoton micrometer-scale photoetching in silicate-based glasses.
AB  - Silicate-based glasses containing approximately 10% by weight boron or more have
      been observed to exhibit selective etching in hydrofluoric acid solution after
      direct exposure to intense visible laser light at 532 nm. The observation of a
      ring-shaped etch pattern in samples exposed to solid Gaussian beams suggests that
      selective etching is related to a charge-diffusion process rather than to local
      light-induced defect generation. The technique has so far resulted in the
      maskless production of micrometer-scale features with submicrometer depths.

PMID- 19859149
TI  - Rotating vector solitary waves in isotropic fibers.
AB  - The properties of elliptically polarized solitary waves in isotropic optical
      fibers are investigated. Two families of polarized solitary pulses are
      identified, but only one of them is shown to be stable. These pulses are
      characterized by a fixed polarization pattern that rotates at a constant rate as
      the pulse propagates down the fiber. The evolution of the polarization of these
      pulses is important for the operation of short-pulse fiber lasers and other
      nonlinear devices.

PMID- 19859150
TI  - General classes of double phase conjugation.
AB  - The double phase-conjugate mirror (DPCM) is a stimulated four-wave mixing effect,
      mediated by either a chi(3) mechanism or a photorefractive effect. The type of
      grating that operates in the DPCM can be a transmission or reflection grating,
      depending on the wave-mixing configuration. Any combination of nonlinearity and
      grating geometry is possible, so that four general DPCM classes emerge. An
      analytic solution of the last unsolved class, the photorefractive reflection
      DPCM, is presented. With these results, general observations concerning the four
      categories of double phase conjugation are made. An important conclusion is that
      the type of grating geometry and its associated boundary conditions dictate many
      of the basic features of the DPCM, regardless of the nonlinearity involved.

PMID- 19859151
TI  - L-Histidine tetrafluoroborate: a solution-grown semiorganic crystal for nonlinear
      frequency conversion.
AB  - The crystal structure, refractive indices, and phase-matching conditions for a
      new nonlinear optical material, L-histidine tetrafluoroborate (HFB), are
      reported. HFB grows readily, displays favorable mechanical characteristics, and
      has adequate birefringence to permit phase-matched parametric processes over much
      of its transparency range (250 nm to 1300 nm). The phase-matching loci and
      angular sensitivity for second-harmonic generation of 1064-nm light in single
      crystals of HFB were measured. The effective nonlinearity for HFB is comparable
      with that of beta-barium borate (~2 pm/V), and its angular sensitivity
      [delta(Deltak)/deltatheta] is somewhat smaller.

PMID- 19859152
TI  - Excited-state enhancement of the third-order nonlinear optical susceptibility of
      nonether polyphenylquinoxaline.
AB  - The microscopic third-order nonlinear-optical susceptibility gamma(-omega; omega,
      omega, -omega) of a conjugated polymer, nonether polyphenylquinoxaline, was
      observed to be enhanced by two times from 355-nm optically pumped excited-state
      populations under the condition of unsaturated pumping. We studied the time
      evolution of the enhancement and verified by a fluorescence measurement that the
      excited-state enhancement of gamma(-omega; omega, omega, -omega) is proportional
      to the population of the excited state.

PMID- 19859153
TI  - Interactions of bound multiple solitons in strongly birefringent fibers.
AB  - We report the observation of the interaction of bound multiple solitons generated
      by orthogonally polarized, highamplitude pulses in strongly birefringent fibers.
      For the birefringence used, the threshold amplitude for the interaction is higher
      than that of the onset of second-order solitons on each axis. The characteristics
      of the output pulses are in good agreement with the results of a numerical
      simulation of this interaction. A general investigation of this effect is carried
      out at high values of birefringence, and it is found numerically that, even
      though the system is nonintegrable, the description of its evolution appears to
      be reduceable to a finite number of effective degrees of freedom.

PMID- 19859154
TI  - Effect of frequency sliding and filtering on the interactions of polarization
      division-multiplexed solitons.
AB  - I analyze by numerical simulation and perturbation theory the effect of frequency
      sliding filters on the interactions between orthogonally polarized solitons. It
      is found that strong filters may substantially increase the collision distance.

PMID- 19859155
TI  - Generation of ultrashort second-harmonic pulses by compressing the Cerenkov
      output.
AB  - Ultrashort optical second-harmonic pulses based on a traditional phase-matched
      Cerenkov second-harmonic generation scheme, with an additional prism to equalize
      the arrival time, are proposed. Proton-exchanged KTP, LiNbO(3) waveguides, and
      several prism materials are considered in the evaluation. There is no constraint
      on crystal length, making high efficiency possible as well as preserving an
      ultrashort pulse width. The proposed approach may be a practical and efficient
      way to achieve convenient ultrashort harmonic pulses.

PMID- 19859157
TI  - Soliton polarization rotation in fiber lasers.
AB  - I have found the approximate analytical solution in explicit form for a vector
      soliton with an arbitrary component ratio. My solution describes the dependence
      of soliton intensity on polarization angle and also nonlinear polarization
      rotation. The analytical results agree well with the numerical simulations.

PMID- 19859156
TI  - Origin and elimination of dynamic instability in a self-pumped phase-conjugate
      mirror.
AB  - The origin and the elimination of dynamic instability have been experimentally
      studied in a self-pumped phase-conjugate mirror (SPPCM) of a Cu:KNSBN crystal.
      Experimental results show that the dynamic instability of the SPPCM arises from
      the competition between the self-generated fanning effect and SPPCM formation.
      The ordinary-polarized component of a partially extraordinary-polarized incident
      light beam can act to decrease the self-generated fanning effect of the
      photorefractive crystal. We can eliminate the dynamic instability of the SPPCM by
      restraining the self-generated fanning effect with a partially extraordinary
      polarized incident light beam.

PMID- 19859158
TI  - Highly efficient quasi-phase-matched second-harmonic generation by frequency
      doubling of a high-frequency superimposed laser diode.
AB  - We report highly efficient blue-light generation by frequency doubling of a high
      frequency superimposed laser diode, stabilized by a grating feedback technique,
      in a periodically domain-inverted LiTaO(3) waveguide. To increase second-harmonic
      generation conversion efficiency, we enhanced the peak power of the laser diode
      by using a gain-switching method. Locking the oscillation wavelength of the laser
      diode by the grating feedback technique, we obtained 4.5 mW of average blue-light
      power with 13% conversion efficiency.

PMID- 19859159
TI  - Monolithic integration of microlens arrays and fiber holder arrays in poly(methyl
      methacrylate) with fiber self-centering.
AB  - For many fiber applications the precise spacing from one fiber to another and the
      collimation of the outgoing light are important subjects. In the case of three
      dimensional arrangements, such as fiber arrays, the complexity increases. The
      method of proton irradiation of poly(methyl methacrylate) permits the fabrication
      of slightly fan-shaped fiber holder arrays that can correct inhomogeneities of
      the fiber diameters in the micrometer range. Even a three-dimensional monolithic
      integration of fiber holders and corresponding microlenses can be achieved.

PMID- 19859160
TI  - Optical fiber polarizer based on highly birefringent single-mode fiber.
AB  - An in-line fiber polarizer is proposed and demonstrated. The attenuation of a
      single-mode fiber experiencing an axial periodic perturbation shows peaks at
      certain wavelengths, resulting from the power coupling between the guided mode
      and the cladding modes. When the fiber has significant linear birefringence, each
      of these peaks is split into two peaks. The fiber thus exhibits polarization
      selective attenuation characteristics. An example of such a polarizer is
      demonstrated based on a highly birefringent fiber with a beat length of 1.3 mm. A
      25-dB polarization extinction ratio is obtained, with an attenuation of 1.3 dB at
      an operating wavelength of 1177 nm.

PMID- 19859161
TI  - Experimental investigation of picosecond pulse reflection from fiber gratings.
AB  - The dispersion of picosecond pulses on reflection from efficient photorefractive
      fiber gratings is explored experimentally. Unlike simple measurements of
      reflectivity, this approach allows both the amplitude and the phase of the
      grating response to be probed as a function of frequency.

PMID- 19859162
TI  - Non-Gaussian corrections to the Gordon-Haus distribution resulting from soliton
      interactions.
AB  - In a soliton transmission system, spontaneous emission noise owing to optical
      amplifiers leads to timing jitter that is usually assumed to be Gaussian
      distributed. It is shown that the mutual interaction of solitons in neighboring
      time slots can lead to non-Gaussian tails on the distribution function and to a
      substantial increase in the bit-error rate. It is argued that the approach used
      here will also be of use in the study of non-return-to-zero systems.

PMID- 19859163
TI  - Push-pull integrate-optics Mach-Zehnder interferometer with domain inversion in
      one branch.
AB  - We report on a push-pull integrated-optics Mach-Zehnder interferometer having one
      domain-inverted branch and one noninverted branch. It is fabricated in the c(+)
      side of a LiNbO(3) substrate. We achieve ferroelectric domain inversion in one
      branch of the waveguide by doping it more heavily with Ti than the other branch
      and by using a high-temperature treatment that raises the temperature above the
      doped Curie temperature of the one branch but not of the other. The cumulative
      electro-optic effect of the inverted branch is found to be opposite that in the
      noninverted branch when both are subjected to the same electric field.

PMID- 19859164
TI  - Epitaxial Ba(2)NaNb(5)O(15) thin film by pulsed laser deposition and its
      waveguide properties.
AB  - An epitaxial Ba(2)NaNb(5)O(15) thin film with excellent crystalline properties
      has been achieved on a (001) KTiOPO(4) substrate by use of the technique of
      pulsed laser deposition. X-ray-diffraction analysis has revealed that (110)
      oriented Ba(2)NaNb(5)O(15) film was produced. The film has good optical
      transmitting characteristics and a propagation loss as low as 1.08 dB/cm. The
      noncritical phase-matching feature in the second-harmonic generation process in
      the film waveguide has also been studied.

PMID- 19859166
TI  - Design for a compact tunable Ti:sapphire laser.
AB  - Tunable laser radiation with megahertz linewidth is generated with a simple,
      inexpensive, and compact laser system that uses two common microscope slides as
      the only intracavity tuning elements. The laser emits two radiation modes whose
      frequencies are separated by 1.2 GHz, corresponding to the free spectral range of
      the laser resonator. The frequencies may be rapidly varied over a range of 1.5
      GHz at a rate of 2 GHz/s.

PMID- 19859165
TI  - Ce(3+):LuLiF(4) as a broadband ultraviolet amplification medium.
AB  - Ce(3+):LuLiF(4) is shown to have a broad gain spectrum, which is attractive for
      short-pulse applications. A large small-signal gain over 6 dB/cm and a
      sufficiently large saturation fluence of 50 mJ/cm(2) were observed for 10-ns
      probe pulses under KrF excimer laser pumping. In a confocal four-pass
      configuration, 17-dB amplification was demonstrated for 325-nm picosecond pulses,
      and 20-dB gain was demonstrated for cw laser light.

PMID- 19859167
TI  - 1.4-kW Nd:YAG slab laser with a diffusive closed-coupled pump cavity.
AB  - A high-power high-efficiency Nd:YAG slab laser with lamp pumping is developed by
      use of a novel diffusive-closed coupled lamp pump cavity. In cw-mode operation,
      1.45 kW of output power is obtained with a slope efficiency of 5.0%. In pulsed
      mode operation (50 pulses/s, 25% pulse duty), 1.4 kW of output power is obtained
      with a slope efficiency of 4.3%. The output power per unit volume is 45 W/cm(3).
      To our knowledge, these output powers and the power per unit volume are the
      highest obtained for the single-head Nd:YAG slab laser with lamp pumping.

PMID- 19859168
TI  - Smart-pixel spatial light modulator for incorporation in an optoelectronic neural
      network.
AB  - We present the design, fabrication, and testing of a novel liquid-crystal-on
      silicon optically addressed spatial light modulator for use as a weight matrix in
      an ART-1 optoelectronic neural processor. Each pixel in the 50 x 83 element array
      occupies 75 microm x 75 microm and consists of a photodetector, a threshold
      circuit, a 1-bit (flip-flop) memory element, and a liquid-crystal modulating
      mirror. The array is designed to switch all the pixels initially to the ON state.
      Subsequently each pixel is independently switched to the OFF state if a
      superthreshold amount of light falls upon the pixel's photodetector. The device
      has a contrast ratio of 20:1, a switch-on time (10-90% rise time) of 500 micros,
      and a switch-off time of ~500 micros (depending on the externally set threshold).
      Measured device uniformities and interpixel coupling are also described.

PMID- 19859169
TI  - Pulse compression and spatial phase modulation in normally dispersive nonlinear
      Kerr media.
AB  - Numerical simulations show that, because of the spatiotemporal coupling implied
      by the multidimensional nonlinear Schrodinger equation, self-focusing of
      ultrashort optical pulses can lead to pulse compression even in the normal
      dispersion regime of a nonlinear Kerr medium. We show how this coupling can be
      further exploited to control the compression by use of spatial phase modulation.
      Both the compression factor and the position at which the minimum pulse width is
      realized change with the amplitude of the phase modulation.

PMID- 19859170
TI  - Space-time focusing of femtosecond pulses in a Ti:sapphire laser.
AB  - We present what is to our knowledge the first three-dimensional model of a
      femtosecond pulse propagating in a Ti:sapphire laser crystal, which includes
      dispersion, self-focusing, and finite response time of the medium and does not
      assume the slowly varying envelope approximation. The combined action of material
      dispersion and phase modulation leads to a dramatic space-time focusing on the
      pulse. Dispersion prevents catastrophic selffocusing and self-steepening of the
      pulse, even though the peak power of the pulse is much greater than the critical
      power for self-focusing filamentation. Extrapolation of these results to shorter
      pulse durations shows that this space-time focusing mechanism can operate even
      for pulses with durations close to the response time of the Kerr nonlinearity.

PMID- 19859171
TI  - Femtosecond vacuum-ultraviolet pulse measurement by field-ionization dynamics.
AB  - Three techniques are demonstrated for measuring femtosecond pulses from the deep
      vacuum ultraviolet to the visible based on the ionization dynamics of optical
      field-ionized plasmas. A probe pulse propagates through a plasma generated by an
      intense femtosecond KrF excimer laser pump pulse. Ionization-induced defocussing
      or collisional absorption yield a cross-correlation measurement of the probe
      pulse. Ionization-induced spectral blue shifting of the probe can give an upper
      limit for the probe pulse duration.

PMID- 19859172
TI  - Subfeature speckle interferometry.
AB  - A novel speckle technique, subfeature speckle interferometry, is introduced that
      relies on the amplitude interference of two independent speckle patterns,
      originating from coherent illumination, by use of an optical system that produces
      interferometric quality interference fringes on a scale comparable with the
      speckle correlation length. Examples are given for in-plane translation, sample
      tilt, and temperature measurement (strain). A temperature measurement accuracy
      sigma = 0.92 degrees C is realized. In contrast to traditional full-field speckle
      crosscorrelation techniques, this technique requires only a small number of
      detector elements with minimal signal processing and is compatible with many real
      time sensor applications.

PMID- 19859173
TI  - Technique for the removal of speckle phase in electronic speckle interferometry.
AB  - It is shown that the speckle nature of electronic speckle pattern interferometry
      images can be reduced in quasireal time with the use of only three consecutive
      video images. By use of additive-subtractive phase modulation processing the
      technique is essentially insensitive to environmental noise, and distortion of
      fringes does not occur. By further removing the random speckle phase we show,
      using speckle statistics, that the number of dark speckles in the resulting
      fringe pattern is close to zero.

PMID- 19859174
TI  - Simple coherence measurement with a modified Lau interferometer.
AB  - We measure mutual intensity in quasi-monochromatic light. Our setup is simple,
      without a lens. A rotating grating and a one-dimensional receiver are the only
      pieces of hardware. The action of our system can be understood as that of a mock
      Lau interferometer.

PMID- 19859176
TI  - Off-axis holographic technique for particle image velocimetry using a Fourier
      transform lens.
AB  - We propose and demonstrate a simple off-axis scheme for particle field holography
      that utilizes the particle forward scattering by means of a Fourier transform
      lens for both recording and reconstruction. This technique has the advantages of
      both the low speckle noise offered by off-axis holography and the minimal laser
      power requirement characteristic of in-line illumination.

PMID- 19859175
TI  - T violation and microhertz resolution in a ring laser.
AB  - A He-Ne ring laser has given the Earth-rotation-induced Sagnac frequency to a
      precision of 1 microHz, or 2 parts in 10(8), 2 x 10(-21) of the laser frequency.
      Because the beat frequency in a ring laser originates in either timereversal or
      (with a more complicated polarization geometry) parity-violating effects, such
      systems have the potential of detecting ultrasmall symmetry violations.

PMID- 19859177
TI  - Optical restoration of photorefractive holograms through self-enhanced
      diffraction.
AB  - For the first time to our knowledge, we demonstrate the use of self-enhanced
      diffraction to optically restore weak dynamic volume holograms. This restoration
      process is achieved through the use of a novel beam-toggling scheme that
      significantly enhances the steady-state diffraction efficiency of volume index
      gratings stored in photorefractive media. Experiments demonstrating and
      confirming theory are presented and discussed.

PMID- 19859178
TI  - Simultaneous strain and temperature sensing with photogenerated in-fiber
      gratings.
AB  - A new technique for simultaneous strain and temperature sensing is demonstrated.
      The approach employs two different types of photogenerated fiber grating, namely,
      a fiber Bragg grating and a fiber polarization-rocking filter. The method relies
      on the different dependencies of the fiber refractive index and birefringence on
      strain and temperature. Both of these measurands can be determined from the
      effect that they have on the resonant wavelength of each grating. The information
      is provided in the frequency domain, avoiding the problem of limited unambiguous
      signal range associated with the use of competing optical fiber interferometers.

PMID- 19859179
TI  - Intelligent photonic switch based on polarization-selective birefringent computer
      generated holograms.
AB  - We designed and implemented an intelligent reflecting 2 x 1 photonic switch using
      polarization-selective birefringent computer-generated holograms combined with
      two polarization modulators. In functional terms, the reflecting switch provides
      a through path to the output when only one incoming link is transmitting. When
      both incoming links attempt transmission, the switch turns reflecting, thereby
      permitting a full exchange of the two incoming streams. The switch can also be
      set to detect backpropagating beams at its output, to split the beam evenly, and
      to route the two resulting beams to each of the two inputs. The switch is useful
      for ultrafast fault-tolerant photonic network applications.

PMID- 19859180
TI  - Co(2+):YSGG saturable absorber Q switch for infrared erbium lasers.
AB  - Passive Q switching of Er:glass (1.53 microm) with a new, robust, solid-state
      saturable absorber, Co(2+):Y(3)Sc(2)Ga(3)O(12), has been demonstrated. Q-switched
      pulses of 20 ns and 4 mJ of energy were obtained. An absorption cross section of
      5 x 10(-20) cm(2) was measured. Preliminary results for a Co(2+):Y(3)Al(5)O(12)
      saturable absorber Q switch are also discussed.

PMID- 19859181
TI  - High-speed liquid-crystal-on-silicon spatial light modulators using high-voltage
      circuitry.
AB  - Two high-speed liquid-crystal-on-silicon spatial light modulators that use high
      voltage circuitry are described. The high-voltage circuits used can provide 30
      and 15 V for switching chiral smectic liquid-crystal spatial light modulators
      with 10-90% switching times of 30 and 50 micros, respectively. The ON/OFF
      contrast ratios are 13:1 and 15:1.

PMID- 19859182
TI  - 82% Efficient continuous-wave frequency doubling of 1.06 microm with a monolithic
      MgO:LiNbO(3) resonator: errata.

PMID- 19859183
TI  - Nonlinear zeros in second-harmonic generation at grating couplers.

PMID- 19859184
TI  - Self-starting of passively mode-locked lasers with fast saturable absorbers.

PMID- 19859185
TI  - Highly efficient second-harmonic generation of ultraintense Nd:glass laser
      pulses.

PMID- 19859186
TI  - Specular nonlinear anisotropic polarization effect along fourfold crystal
      symmetry axes.

PMID- 19859187
TI  - Sequence dependence of phase-induced intensity noise in optical networks that
      employ direct modulation.

PMID- 19859188
TI  - Bandpass switching in a nonlinear-optical loop mirror.

PMID- 19859189
TI  - Strong effect of output coupling on the performance of metal-clad waveguide
      polarizers.

PMID- 19859191
TI  - Versatile, efficient, diode-pumped miniature slab laser.

PMID- 19859190
TI  - Integrated-optic dispersion compensator that uses chirped gratings.

PMID- 19859192
TI  - Sensitivity of lasing in neonlike zinc at 21.2 nm to the use of the prepulse
      technique.

PMID- 19859193
TI  - Continuous and discrete wavelength tuning in Er:Yb fiber Fabry-Perot lasers.

PMID- 19859194
TI  - Bandwidth studies of an injection-seeded b -barium borate optical parametric
      oscillator.

PMID- 19859196
TI  - Polarization properties of a twisted fiber laser.

PMID- 19859195
TI  - Effect of temperature on amplification characteristics of Pr (3+) -doped fiber
      amplifiers.

PMID- 19859197
TI  - Ti:sapphire regenerative amplifier for ultrashort high-power multikilohertz
      pulses without an external stretcher.

PMID- 19859198
TI  - Measurement of group-velocity walk-off of short pulses in nonlinear crystals: a
      novel method.

PMID- 19859199
TI  - Amplification of sub-100-TW femtosecond pulses by shifted amplifying Nd:glass
      amplifiers: theory and experiments.

PMID- 19859200
TI  - Soliton and collapse regimes of pulse generation in passively mode-locking laser
      systems.

PMID- 19859201
TI  - Distortion-invariant composite filter for detecting a target in nonoverlapping
      scene noise.

PMID- 19859202
TI  - Imaging through random media by use of low-coherence optical heterodyning.

PMID- 19859203
TI  - Cross-correlation technique for single-shot measurements of weak light pulses.

PMID- 19859205
TI  - Detection of atomic interference through collective radiation.

PMID- 19859204
TI  - Highly precise 1-THz optical frequency-difference measurement of 1.5- mu m
      molecular absorption lines.

PMID- 19859206
TI  - Fiber-optic sensor array without polarization-induced signal fading.

PMID- 19859207
TI  - Compact in-line interferometer for low-coherence reflectometry.

PMID- 19859208
TI  - Pseudonondiffracting slitlike beam and its analogy to the pseudonondispersing
      pulse.
AB  - A new nonspreading beam is proposed for the case in which diffraction occurs only
      in one transverse coordinate. The beam has the shape of a pulse in one dimension
      and is constant in the other (slitlike shape). The intensity of the pulse's peak
      remains almost constant along a finite interval on the propagation axis. The
      proposed beam is analyzed and demonstrated experimentally. The analogy between
      this beam and the temporal pulse in a dispersive medium is discussed.

PMID- 19859209
TI  - Experimental images of heterogeneous turbid media by frequency-domain diffusing
      photon tomography.
AB  - We present images of heterogeneous turbid media derived from measurements of
      diffuse photon-density waves traveling through highly scattering tissue phantoms.
      To our knowledge, the images are the first experimental reconstruction based on
      data collected in the frequency domain. We demonstrate images of both absorbing
      and scattering heterogeneities and show that this method is sensitive to the
      optical properties of the heterogeneity. The algorithm employs a differential
      measurement scheme that reduces the effect of errors resulting from incorrect
      estimation of the background optical properties. The relative advantages of
      sources with low and high modulation frequency are discussed within this context.

PMID- 19859210
TI  - Three-dimensional ordered patterns by light interference.
AB  - Based on numerical simulation it is found that three-dimensional periodic
      patterns with micrometer or submicrometer lattice constants, such as those with
      simple cubic, face-centered cubic, body-centered cubic, or body-centered
      tetragonal symmetry, can be formed by use of multiple laser beam interference.
      Changes in the number and angle of the incident beams result in different spatial
      patterns, whereas variation of the incident wavelength affects only the lattice
      constant of the patterns. Face-centered cubic and body-centered tetragonal
      patterns have been observed experimentally. Our results, combined with the
      optical trapping of dielectric particles, might provide a promising approach to
      the realization of a new kind of material-a photonic crystal.

PMID- 19859211
TI  - Model of amplified scattering in photorefractive media: comparison of numerical
      results and experiment.
AB  - We implement a random-walk scattering model in a nonlinear beam-propagation code
      to simulate fanning in photorefractive crystals. The characteristics of the
      scatterers were verified by comparisons of the measured firstorder statistics of
      the scattered intensity with a theoretical expression of the probability-density
      function based on a random-walk scattering model. Both the size and the
      separation of the scatterers can be varied, enabling us to tailor our numerical
      simulations to experimental measurements of nonamplified and amplified
      scattering. We show that a one-dimensional model does not accurately simulate
      amplified scattering for crystals with a nondiagonal electro-optic tensor and
      that surface scattering alone may not account for the angular dependence of the
      amplified scattering distributions.

PMID- 19859212
TI  - Two-photon absorption and optical-limiting properties of novel organic compounds.
AB  - The optical-limiting behavior and two-photon absorption properties of four novel
      organic compound solutions in tetrahydrofuran have been investigated. An
      ultrashort laser source with 0.5-ps pulse width and 602-nm wavelength was
      employed. The transmissivities of the various 1-cm-thick solution samples have
      been measured as a function of the beam intensity as well as of the solute
      concentration. The measured results can be fitted on the assumption that two
      photon absorption is the only predominant mechanism causing the observed
      opticallimiting behavior. Based on the intensity-dependent transmissivity
      measurements, the molecular two-photon absorption coefficients for the four
      compounds are presented.

PMID- 19859213
TI  - Modulational instability in second-harmonic generation.
AB  - We show that the eigenmodes of the two-wave interaction in a dispersive quadratic
      medium are unstable with respect to periodic perturbations. This mechanism
      represents a novel kind of modulational instability that involves the spontaneous
      generation of sideband pairs around both the fundamental and the second-harmonic
      frequencies.

PMID- 19859214
TI  - Self-induced optical gratings in nematic liquid crystals with a feedback mirror.
AB  - Spontaneous transverse one-dimensional optical grating formation has been
      observed in slightly asymmetric single-feedback mirror experiments using nematic
      liquid crystals as nonlinear optical media. It is shown that weak asymmetries can
      be compensated by increasing the intensity and transition from one-dimensional
      gratings to two-dimensional patterns.

PMID- 19859215
TI  - Measurement of the phase of second-harmonic generation in SK5 glass.
AB  - Focusing an intense laser beam and its second harmonic into a SK5 glass slab
      transforms the glass into a frequency doubler. We present a new method to measure
      the optical phase between the second-harmonic beam that transformed the glass and
      the second-harmonic beam subsequently generated by the glass. We find this phase
      shift to be Deltatheta= -90 degrees +/- 7 degrees . A spatial map of this phase
      confirms that the internal dc electric field locked inside the glass resembles a
      dipole electric field.

PMID- 19859216
TI  - Low-noise photorefractive amplification and detection of very weak signal beams.
AB  - We present theoretical and experimental analyses of the signal-to-noise ratio
      (SNR) of photorefractive two-wave mixing detection that uses BaTiO(3). The
      influence of beam fanning is taken into account in the detection process.
      Different known methods to enhance the SNR of the detection are theoretically and
      experimentally compared. A 10-fold improvement of the SNR is obtained, and the
      detection of a 1-pW signal intensity for a SNR of 50 is achieved for two of them.

PMID- 19859217
TI  - Solitary waves in a single-mode fiber with two-photon absorption and bandwidth
      limited optical gain.
AB  - The exact soliton solutions of the nonlinear Schrodinger equation and the
      extended nonlinear Schrodinger equation with two-photon absorption and bandwidth
      limited optical gain, respectively, are given. The results show that both
      picosecond and femtosecond soliton pulses can be propagated in a single-mode
      fiber with twophoton absorption and symmetric optical gain with the proper
      spectral profile.

PMID- 19859218
TI  - Exact separation of surface and bulk contributions to anisotropic second-harmonic
      generation from cubic centrosymmetric media.
AB  - We solve this long-standing problem theoretically by recognizing that the ranks
      of the tensors that describe the surface and bulk second-order nonlinear
      susceptibilities differ in this class of media. We show that this implies that
      the phenomenologies of the anisotropic optical second-harmonic (SH) responses of
      the two sources differ for all possible crystal facial orientations except (111).
      To demonstrate the result, we apply the theory to separate the surface and bulk
      contributions to SH generation from an oxidized vicinal Si(001) wafer for p
      polarized 775-nm fundamental and s-polarized SH radiation. It is shown that
      knowledge of the phase of the SH field is necessary to achieve a unique
      separation.

PMID- 19859219
TI  - Nonlinear self-phase-modulation effects: a vectorial first-order perturbation
      approach.
AB  - A full-vectorial integral expression is derived to compute the effective mode
      area of any Kerr-type nonlinearoptical waveguide working in a self-phase
      modulation regime. In order to highlight the correction brought by the vectorial
      approach in a strong guidance situation, we compare the effective area of a
      tapered fiber computed by the usual scalar expression with the one obtained with
      the full-vectorial approach.

PMID- 19859220
TI  - 40-W cw, TEM(00)-mode, diode-laser-pumped, Nd:YAG miniature-slab laser.
AB  - We have built a diode-laser-pumped Nd:YAG slab laser that emits 40 W of cw power
      in a TEM(00) mode and 72 W of power in multimode operation when pumped with 235
      W. The slope efficiencies are 22% for TEM(00)-mode operation and 36% for
      multimode operation. The laser uses a zigzag slab geometry to reduce thermally
      induced distortions and operates at less than one wave of distortion at the full
      pump power. A significant advantage of our design over those of previous slab
      lasers is a new Teflon AF protective coating on the slab total-internal
      reflection surfaces, which greatly simplifies the mounting and cooling of the
      slab laser medium.

PMID- 19859221
TI  - Amplitude and frequency stability of a diode-pumped Nd:YAG laser operating at a
      single-frequency continuous-wave output power of 20 W.
AB  - Amplitude and frequency noise of an injection-locked diode-pumped Nd:YAG ring
      laser operating at a singlefrequency output power of 20 W cw are investigated.
      This laser system will be used as a light source for an interferometric
      gravitational-wave detector.

PMID- 19859222
TI  - Simple high-efficiency TEM(00) diode-laser-pumped Q-switched laser.
AB  - A simple, efficient diode-laser-pumped Q-switched Nd:YAG laser is described that
      produces 2.25-mJ, TEM(00), 4-ns pulses up to 90 Hz with only 20 mJ of pump power.
      The laser has a zigzag slab geometry, side pumped with only one high-power quasi
      cw diode bar. This performance approaches that of longitudinal pumping,
      demonstrating TEM(00) mode operation with long-pulse and Q-switched slope
      efficiencies of 28% and 19%, respectively. Secondand fourth-harmonic efficiencies
      of >50% and >20% from 1064 nm without the use of external focusing optics were
      also demonstrated.

PMID- 19859223
TI  - Pr(3+)-doped GeS(x)-based glasses for fiber amplifiers at 1.3 microm.
AB  - The photoluminescence properties of Pr(3+)-doped GeS(x)-based glasses are studied
      and compared with those of other sulfide and fluoride glasses. The possibility of
      highly pump-power-efficient fiber amplifiers based on these GeS(x)-containing
      glasses in the telecommunications window at 1.3microm is discussed.

PMID- 19859224
TI  - High-power erbium-doped fiber laser mode locked by a semiconductor saturable
      absorber.
AB  - Using an erbium-doped fiber laser (EDFL) passively mode locked by a semiconductor
      saturable absorber, we generate 5.5-ps pulses of a 2.3-nJ/pulse, which are more
      than three times higher in energy than for other reported EDFL's. We show that,
      by introduction of a linear loss element within the cavity, multiple pulsing
      behavior at high pump powers can be suppressed. We also determine the saturable
      absorber characteristics-absorbance versus wavelength near band gap-that are
      necessary to produce short mode-locked pulses.

PMID- 19859225
TI  - Continuous-wave diode-laser injection-seeded beta-barium borate optical
      parametric oscillator: a reliable source for spectroscopic studies.
AB  - A beta-barium borate optical parametric oscillator pumped by the third harmonic
      of a pulsed Nd:YAG laser and seeded by a cw diode laser is described. It operates
      on a single longitudinal mode of its cavity, with a linewidth lower than 500 MHz
      (0.017 cm(-1)). The conversion efficiency of the device is as great as 20% on
      signal output alone. The seeded tuning range is limited by the diode's
      tunability.

PMID- 19859226
TI  - Identifying the output spectra from end facets of semiconductor lasers.
AB  - We report a simple way of determining the spontaneous-emission spectrum from the
      output spectrum directly detected at the end facet of a semiconductor laser and
      measuring the wavelength difference between the peaks of the gain and the
      spontaneous emission. This difference can be used to explain the blue shift of
      the peak wavelength of the output spectrum after the facets of the diode have
      been antireflection coated during the process of making a traveling-wave
      semiconductor amplifier.

PMID- 19859227
TI  - High-repetition-rate femtosecond mid-infrared pulse generation.
AB  - Ultrashort mid-infrared pulses at a repetition rate of 82 MHz have been generated
      by difference-frequency mixing at the output of a single-cavity, two-color
      femtosecond Ti:sapphire laser. The center wavelengths of the midinfrared pulses
      are tunable from 7.5 to 12.5 microm. Their pulse durations range from 450 to 650
      fs, as a function of the center wavelength.

PMID- 19859228
TI  - Phase and intensity characterization of femtosecond pulses from a chirped-pulse
      amplifier by frequency-resolved optical gating.
AB  - Frequency-resolved optical gating (FROG) measurements were made to characterize
      pulses from a Ti:sapphire chirped-pulse amplified laser system. By characterizing
      both the pulse intensity and the phase, the FROG data provided the first direct
      observation to our knowledge of residual phase distortion in a chirped-pulse
      amplifier. The FROG technique was also used to measure the regenerative amplifier
      dispersion and to characterize an amplitude-shaped pulse. The data provide an
      experimental demonstration of the value of FROG for characterizing complex
      pulses, including tailored femtosecond pulses for quantum control.

PMID- 19859229
TI  - Ultrashort-pulse measurement using noninstantaneous nonlinearities: Raman effects
      in frequency-resolved optical gating.
AB  - Ultrashort-pulse-characterization techniques generally require instantaneously
      responding media. We show that this is not the case for frequency-resolved
      optical gating (FROG). We include, as an example, the noninstantaneous Raman
      response of fused silica, which can cause errors in the retrieved pulse width of
      as much as 8% for a 25-fs pulse in polarization-gate FROG. We present a modified
      pulse-retrieval algorithm that deconvolves such slow effects and use it to
      retrieve pulses of any width. In experiments with 45-fs pulses this algorithm
      achieved better convergence and yielded a shorter pulse than previous FROG
      algorithms.

PMID- 19859230
TI  - Time-resolved multichannel imaging of fluorescent objects embedded in turbid
      media.
AB  - We present a multichannel detection technique for three-dimensional imaging of
      objects embedded in turbid media by using time-resolved fluorescence. By using a
      streak camera, we can obtain the experimental data in a single measurement. The
      data, analyzed by means of a triangulation algorithm, provide accurate
      localization of a fluorescent object for path lengths of up to 120 scattering
      mean free paths. The results demonstrate the feasibility of combining
      fluorescence spectroscopy with time-resolved optical tomography for localizing
      and identifying embedded objects.

PMID- 19859231
TI  - Optical imaging through highly scattering media by use of heterodyne detection in
      the 1.3-microm wavelength region.
AB  - Optical imaging through highly scattering media was studied in the 1.3-microm
      wavelength region by use of a continuous-wave Nd:YAG laser and an optical
      heterodyne detection technique. We measured and compared the extinction
      coefficients of the fat emulsion Intralipid-10% at 0.80, 1.064, and 1.319 microm
      and demonstrated that the low scattering at 1.319 microm will permit optical
      imaging through highly scattering media, which otherwise may not be achieved. A
      possible use of water absorption at 1.319 microm to image the interior structure
      of biological tissues is also presented and discussed.

PMID- 19859232
TI  - Fourier transformation with a planar holographic doublet.
AB  - The use of a single off-axis holographic lens for Fourier transformation results
      in phase errors that degrade its performance. A configuration of two identical
      off-axis holographic elements is proposed for performing Fourier transformation
      without phase errors. Such a configuration can be readily folded to form a
      compact and cascadable element that can be conveniently incorporated into optical
      correlators. The grating functions of the holographic elements needed for
      performing the desired transformation were used to record the planar
      configuration, which was then experimentally evaluated. The results reveal that
      phase errors were indeed eliminated, in close agreement with the calculations.

PMID- 19859233
TI  - Detection of moving objects embedded within scattering media by use of speckle
      methods.
AB  - Speckle-pattern subtraction methods are used for the detection of moving objects
      embedded in scattering media. Results show that the ability to detect small
      nonstationary objects is greatly enhanced.

PMID- 19859234
TI  - Selective optical detection of n-heptaney/iso-octane vapors by polyimide
      lightguides.
AB  - The optical anisotropy of planar polyimide lightguides in an atmosphere of n
      heptaney/iso-octane is investigated in a transient experiment for pure and
      several mixed-vapor concentrations. The polymer sensor responds only to n-heptane
      and not to iso-octane vapors. However, the presence of the latter affects the
      dynamic behavior of the waveguide anisotropy, which can be fitted by a stretched
      exponential time dependence. The saturation values of the birefringence are an
      absolute measure for the n-heptane concentration and are not affected by the
      presence of the iso-octane vapors.

PMID- 19859235
TI  - Holographic recording and light amplification in doped polymer film.
AB  - We reported an experimental study of holographic recording and signal light
      amplification through higherorder diffracted waves from holographic gratings
      recorded in an acceptor-donor-substituted azobenzene-doped poly(methyl
      methacrylate) thin film.

PMID- 19859236
TI  - Measurement of distributed strain and temperature in a branched optical fiber
      network by use of Brillouin optical time-domain reflectometry.
AB  - A new scheme is proposed for sensing distributed strain and temperature in
      optical fibers. This scheme uses Brillouin scattering as the sensing mechanism
      and a branched optical fiber network as the sensing fibers. Brillouin optical
      time-domain reflectometry makes it possible to distinguish Brillouin-scattered
      light waves from different optical fiber branches in the network when the
      different Brillouin frequency shifts are assigned to each branch. The technical
      feasibility of this scheme is confirmed experimentally for a branched optical
      network composed of two branches connected to a trunk optical fiber.

PMID- 19859237
TI  - Pulse-width modulation drive technique for high-resolution liquid-crystal
      gratings.
AB  - We report the use of a pulse-width modulation drive technique for high-resolution
      liquid-crystal gratings and show how the grating diffraction efficiency depends
      on the duty cycle of the drive signal. We identify a regime in which the
      diffraction efficiency is linearly proportional to the duty cycle, thereby
      providing a linear drive characteristic.

PMID- 19859238
TI  - Analog distorted helix ferroelectric liquid-crystal-on-silicon spatial light
      modulator.
AB  - We report what are to our knowledge the first results from a liquid-crystal-on
      silicon spatial light modulator that uses the distorted helix ferroelectric mode
      to perform analog light modulation. The spatial light modulator is an
      electronically addressed analog 128 x 128 pixel device with which we have
      demonstrated 16 gray levels and contrast ratios of 33:1 in the zeroth diffracted
      order and 6:1 when imaged. The liquid-crystal switching speed in this device is
      approximately 235 micros, which when added to the data load time of 100 micros
      gives a maximum frame rate of approximately 3 kHz.

PMID- 19859239
TI  - Analysis of the polarization group-velocity dispersion effect in polarization
      independent nonlinear-optical loop mirror demultiplexers.
AB  - Polarization-independent two-wavelength nonlinear-optical loop mirrors are
      analyzed theoretically by use of a Jones matrix model. The model is then applied
      to study the effect of fiber polarization group-velocity dispersion and control
      duty cycle on the extinction ratio in nonlinear-optical loop mirror
      demultiplexing.

PMID- 19859240
TI  - Observations of predicted cooperative shifts in optically pumped stimulated
      emissions in Xe: erratum.

PMID- 19859241
TI  - Red sensitivity of dichromated cellulose triacetate as a holographic recording
      material: errata.

PMID- 19859242
TI  - Strehl ratio and visibility in long-baseline stellar interferometry.
AB  - The relationship between Strehl ratio (S), the parameter most often used by those
      in the adaptive optics field, and visibility (V), the parameter of most interest
      to those working in interferometry, is investigated. It is found that if the
      atmospheric turbulence is assumed to be Kolmogorov, V approximately S for high
      Strehl ratios. At low Strehl ratios, both simulations and an analytical
      formulation show that the Strehl ratio underestimates the visibility.

PMID- 19859243
TI  - Characterization of human scalp hairs by optical low-coherence reflectometry.
AB  - Optical low-coherence reflectometry is used to investigate the internal structure
      and optical properties of human scalp hair. Regardless of hair color, the
      refractive index of the cortical region remains within the range of 1.56-1.59.
      The amplitude of the backscattered infrared light coupled into different-colored
      hair confirms the relative melanin content. Discontinuities in the refractive
      index permit identification of distinct structural layers within the hair shaft.

PMID- 19859244
TI  - Simple fiber-optic autocollimation method for determining the focal lengths of
      optical elements.
AB  - A novel simple fiber-optic autocollimation method for determining the focal
      lengths of lenses and objectives is presented. This method is based on the
      intensity sensing of reflected light, photoelectric measurement, and the use of
      single-mode optical fiber. This fiber serves simultaneously as a point light
      source for the formation of a collimated input laser beam and as a receiver that
      is highly sensitive to spatial displacements for the autocollimation
      backreflectance. The method permits us to locate the focal point spatially and to
      determine the back focal length of a focusing optical element with accuracies
      exceeding 1 and 2 microm, respectively, which are confirmed by both experimental
      and analytical investigations.

PMID- 19859245
TI  - Ultralow-loss mirror of the parts-in-10(6) level at 1064 nm.
AB  - We describe an ultralow-loss and high-reflectance mirror at 1064 nm. A Fabry
      Perot cavity is fabricated with two mirrors to measure the finesse and the
      transmission efficiency on resonance. The finesse was cross checked by two
      different methods: measurements of the cavity decay time and of the frequency
      response function. As a result, a loss of 6 +/- 6 x 10(-6) (6 +/- 6 parts in
      10(6), scatter and absorption) and a finesse of 2236 +/- 54 were measured during
      the cavity decay time. This result coincides with that of the response function
      within accuracies cited above. To our knowledge, the loss is the lowest obtained
      at 1064 nm.

PMID- 19859246
TI  - Microlaser microscope using self-detection for confocality.
AB  - The microlaser microscope can use its own source lasers as detectors to provide a
      matched array of confocal apertures. Detection of the laser light by a single
      avalanche photodiode makes the electronics simple. We have implemented this in a
      64 x 312 pixel format as our first demonstration of the device.

PMID- 19859247
TI  - Asymmetric transmission device using Fe-doped KTa(x)Nb(1-x)O(3) crystal.
AB  - A new type of asymmetric optical transmission device based on contradirectional
      two-wave mixing between an incident beam and its backward-scattering beams in Fe
      doped KTa(x)Nb(1-x)O(3) crystal is demonstrated. The transmittance ratio of the
      beams propagating in opposite directions can be adjusted by a change in the angle
      between the incident beam and the c axis; the maximum ratio is nearly 50:1 at
      only one incident beam. Approximate solutions of two opposite transmittances are
      derived and discussed. It is possible to use this device as an optical isolator
      or an optical diode.

PMID- 19859248
TI  - Soliton propagation with up- and down-sliding-frequency guiding filters.
AB  - We analyze the effect of the third-order guiding filter term on soliton
      transmission in optical fibers. We find that this term causes a significant
      difference between the regimes of up- and down-sliding of filter frequency. In
      particular, the use of up-sliding requires less additional amplifier gain than
      down-sliding does, which is preferable in real systems.

PMID- 19859249
TI  - Single-pulse degenerate-cross-phase modulation in a single-mode optical fiber.
AB  - Using a single ultrashort optical pulse propagating through a short
      nonbirefringent single-mode optical fiber, we have observed degenerate-cross
      phase modulation of the two orthogonal circularly polarized components of the
      pulse. The spectral broadening of the two polarization components in the single
      laser pulse is attributed to self-phase modulation (SPM), degenerate-cross-phase
      modulation (DXPM), and interference between SPM and DXPM.

PMID- 19859250
TI  - Homodyne surface second-harmonic generation.
AB  - We demonstrate the application of the homodyne mixing technique to surface second
      harmonic generation. The technique is shown to have advantages for improving the
      signal-to-noise ratio for background and detector-noiselimited experiments, for
      providing real-time measurement of the phase and magnitude of the surface
      susceptibility, and for simultaneously supplying a normalization signal to cancel
      effects that are due to laser drift.

PMID- 19859251
TI  - Efficient degenerate four-wave mixing in a diode-pumped microchip Nd:YVO(4)
      amplifier.
AB  - The process of saturable-gain degenerate four-wave mixing in a diode-pumped
      microchip Nd:YVO(4) amplifier is investigated. To enhance the efficiency of the
      interaction, multipass geometries are employed in which the weak signal beam and
      therefore the conjugate beam experience several passes in the gain medium.
      Degenerate fourwave mixing reflectivities as high as R = 10% and R = 170% have
      been obtained experimentally for 130-W diode pumping with two-pass and four-pass
      geometries, respectively. Finally, the imaging capabilities of the volume
      population hologram written in the Nd:YVO(4) amplifier are demonstrated.

PMID- 19859252
TI  - Spontaneous pattern formation in a thin film of bacteriorhodopsin with mixed
      absorptive-dispersive nonlinearity.
AB  - We have observed the spontaneous formation of transverse spatial patterns in a
      thin film of bacteriorhodopsin with a feedback mirror. Bacteriorhodopsin has a
      mixed absorptive-dispersive nonlinearity at the wavelength used in the
      experiments (633 nm). Threshold values of the incident intensity for observation
      of pattern formation are found from a linear stability analysis of a model that
      describes bacteriorhodopsin as a sluggish saturable nonlinear medium with a
      complex Kerr coefficient. The calculated threshold intensity is in good agreement
      with the experimental observations, and the patterns are predicted to be
      frequency offset from the pump radiation.

PMID- 19859253
TI  - Nonlinear-optical properties of a poly(vinyl alcohol)-polyaniline
      interpenetrating polymer network.
AB  - The nonlinear-optical properties of a semi-interpenetrating polymer network of
      poly(vinyl alcohol) glutaralde-hyde-polyaniline were studied. Large (>/=10(-12)
      cm(2)/W) and fast (<50 ps) refractive optical nonlinearites were observed. The
      potential of this novel material for photonic applications is evaluated.

PMID- 19859254
TI  - Pulse propagation in nonlinear-optical fibers with phase-locked phase-sensitive
      amplifiers.
AB  - Recently the use of periodically spaced, phase-sensitive optical parametric
      amplifiers was proposed for compensating for linear loss in a nonlinear fiber
      optic communication line [Opt. Lett. 18, 803 (1993)]. In the previous analysis,
      in which the stability of a single pulse was investigated, the variation of the
      amplifier phases was neglected. In a physically realizable line, however, the
      phase of each amplifier would most likely be locked to the phase of the signal
      pulse or to the average of the phases of many such pulses. Here an analysis is
      presented in which the amplifier phase is allowed to vary in response to a signal
      pulse's optical phase. The analysis shows that the solitonlike signal pulses
      remain stable even with this additional phase variation.

PMID- 19859255
TI  - Optical clock recovery from a data stream of an arbitrary bit rate by use of
      stimulated Brillouin scattering.
AB  - Using a fiber-optic stimulated-Brillouin-scattering amplifier as an active
      filter, we have demonstrated optical clock recovery from 5-Gbit/s return-to-zero
      format optical data. Definite patterns and pseudorandom bit sequences were
      tested. This scheme requires no prior knowledge of the clock frequency and is
      well suited for operation at higher data rates.

PMID- 19859256
TI  - Wave mixing and beam profile control in a photorefractive waveguide.
AB  - Photorefractive wave mixing in a waveguide geometry with nonguided external pumps
      has been studied experimentally and theoretically. Guided beam amplification has
      been obtained in an iron-doped lithium niobate waveguide. Additionally,
      photorefractive grating couplers that allow the transverse profile of the
      decoupled guided beam to be controlled are demonstrated.

PMID- 19859257
TI  - Pr(3+) upconversion laser performance improvement by use of pump scavenging.
AB  - Using pump power efficiently in a Pr(3+) -doped fluoride fiber upconversion laser
      can raise conversion efficiency and lower pump threshold. Pump scavenging reuses
      the pump power not absorbed in the first pass through a laser cavity. Both theory
      and experiment show that the backreflected pumps have almost the same effect on
      the conversion efficiency as the forward ones and that total backreflection of
      the pumps can lead to a 60% increase in absorbed pump power, a twofold increase
      in output power, and a 40% reduction of threshold.

PMID- 19859258
TI  - Compact 24-kHz copper-laser-pumped Ti:sapphire laser.
AB  - A compact, pulsed Ti:sapphire laser producing 320 mW of average power at a 24-kHz
      repetition rate has been demonstrated, with the output pulses having 50-ns-width
      and 440-W peak power. Use of a novel small-scale copper laser as the pump source
      results in high-efficiency, short-pulse operation without a Q switch, with
      excellent pulse-to-pulse amplitude stability.

PMID- 19859259
TI  - High-frequency-stability laser at 1.5 microm using Doppler-free molecular lines.
AB  - An extended-cavity 1.5-microm semiconductor laser was frequency stabilized to
      saturated-absorption lines of acetylene. Its long-term frequency stability is of
      the order of 10(-12), with a reproducibility of +/-10 kHz. Using the lines of
      C(2)H(2) or HCN, we could obtain such a high stability with the same laser at
      many wavelengths covering the 1.51-1.56-microm band.

PMID- 19859260
TI  - Copper-laser oscillator with adjoint-coupled self-filtering injection.
AB  - A new injection-controlled laser resonator developed to achieve diffraction
      limited beam quality for high-gain short-pulse lasers is reported. The resonator
      is seeded with a short-pulse laser signal by adjoint-coupled injection. The two
      times diffraction-limited injection beam is self-filtered through a prepulse
      cavity propagation to improve its beam quality. The use of a self-imaging
      unstable resonator diminishes the edge-diffraction-induced beam deterioration. A
      beam quality of 1.1-1.3 times diffraction limited is achieved throughout the
      entire 70-ns laser pulse of a 30-W copper-vapor laser.

PMID- 19859261
TI  - High-power cw neodymium-doped fiber laser operating at 9.2 W with high beam
      quality.
AB  - We report on a 9.2-W cw, two-times diffraction-limited, neodymium-doped fiber
      laser operating in the 1.06-microm region. For a silica-based double-clad fiber,
      slope efficiencies of more than 25% are observed for pumping by a diode-laser
      system operating near 810 nm.

PMID- 19859262
TI  - Spot size transformer with a periodically segmented waveguide based on InP.
AB  - We report what is to our knowledge the first optimization of a spot size
      transformer by use of a periodically segmented waveguide for photonic integrated
      circuits based on InP. It is shown that a nonlinear variation of the segmentation
      ratio along the propagation direction allows one to make an adiabatic transition
      of a short length. A simple method based on the study of a beveled edge
      transition is presented for the optimization of such a device. Internal losses in
      the transition region as low as 1.2 dB are obtained between a coupling waveguide
      and a simple heterostructure waveguide, with a very high transition spot size
      expansion factor.

PMID- 19859263
TI  - System for direct measurement of the step response of electronic devices on the
      picosecond time scale.
AB  - We have built a system capable of measuring the step response of III-V electronic
      devices on the picosecond time scale, with no alteration in device design or
      epitaxy. To switch on the device under test (DUT), we have designed and
      fabricated a new type of photoconductor, the recessed-ohmic photoconductor, which
      swings 0.45 V with a 2-ps rise time and maintains constant output voltage for 100
      ps. This switch is monolithically integrated with the DUT. To measure the output
      current of the DUT, we have built a Ti:sapphire-laser-based pump-probe direct
      electro-optic sampling system that has a minimum detectable voltage of 70 microV/
      radicalHz and a measurement bandwidth of 750 GHz. The overall system, comprised
      of the recessed ohmic photoconductor and the electro-optic sampling system, can
      be used to measure the step response of III-V electronic devices on the
      picosecond time scale.

PMID- 19859264
TI  - Ultrafast measurement of nonequilibrium carrier lifetime in an In
      (0.85)Ga(0.15)As/GaAs relaxed superlattice structure.
AB  - We investigate the recombination time of nonequilibrium carriers in a highly
      excited In(0.85)Ga(0.15)As/GaAs relaxed superlattice structure by studying the
      time-resolved infrared reflectivity at 10.6 microm. Using a cross-correlation
      infrared reflectivity technique, we have measured a carrier lifetime of 2.6 +/-
      0.3 ps. Lattice mismatch between In(0.85)Ga(0.15)As and GaAs layers gives rise to
      misfit dislocations, which act as ultrafast recombination centers and result in a
      dramatic decrease of the carrier lifetime.

PMID- 19859265
TI  - Effect of carrier depletion on optical phase conjugation in a semiconductor laser
      amplifier.
AB  - The temporal effect of optical phase conjugation in a semiconductor laser
      amplifier is studied numerically. The conjugate pulse has distortion and
      frequency chirping owing to the carrier depletion induced by the signal pulse.
      Both the pulse-shape distortion and frequency chirping are enhanced as the signal
      power and the injection current increase. We can reduce these two effects by
      increasing the pump power to reduce the carrier-density depletion induced by the
      signal pulse.

PMID- 19859266
TI  - Effects of the injection current profile shape on sidelobes in large-aperture
      semiconductor laser amplifiers.
AB  - Sharply peaked near-field sidelobes are formed when the input optical field
      pattern interacts with the edges of the current stripe in a semiconductor laser
      amplifier. The strength of this interaction is shown theoretically to depend
      principally on the first and second derivatives of the transverse current
      profile, and hence one can suppress the sidelobes by smoothing the sharp edges in
      the current injection.

PMID- 19859267
TI  - Harmonically mode-locked Ti:Er:LiNbO(3) waveguide laser.
AB  - Active mode locking of an Er-diffusion-doped Ti:LiNbO(3) waveguide laser by
      intracavity phase modulation to as high as the fourth harmonic (5.12 GHz) of the
      axial-mode frequency spacing is reported. The diode-pumped, pigtailed, and fully
      packaged laser with a monolithically integrated intracavity phase modulator has a
      threshold of 9 mW (incident pump power E(p) || c) and emits transform-limited
      pulses of >/=3.8-ps width and </=5.6-(p)J pulse energy (gain-switched mode
      locking) at 1602-nm wavelength (E(s) || c). The relative change of the mode
      locking frequency with the temperature is 3.65 x 10(-5)/ degrees C. The mode
      locking acceptance bandwidth is +/-75 kHz near the axial-mode frequency spacing
      at approximately five times the threshold pump power.

PMID- 19859268
TI  - Direct and passive subnanosecond pulse-train generation from a self-injection
      seeded ultraviolet solid-state laser.
AB  - We propose a passive self-injection-seeding scheme for the generation of short
      pulse trains from various pulsed lasers. In this scheme a single subnanosecond
      pulse is generated from a short-cavity seeding laser. The pulse is then returned
      to the same gain medium and amplified regeneratively until the gain is quenched
      completely. Cw operation capability or an external short-pulse seeding laser is
      not required for generation of short-pulse trains. Based on this simple scheme an
      ultraviolet subnanosecond pulse train is directly and passively generated from a
      solid-state laser medium (Ce(3+):LuLiF(4)) pumped by a standard 10-ns laser.

PMID- 19859269
TI  - Sub-10-fs mirror-dispersion-controlled Ti:sapphire laser.
AB  - We demonstrate the generation of nearly bandwidth-limited 8-fs optical pulses
      near 0.8 microm from a self-mode-locked Ti:sapphire laser oscillator, using
      chirped dielectric mirrors for dispersion control. The mode-locking performance
      is described, and limitations are discussed.

PMID- 19859270
TI  - 30-fs pulses tunable across the visible with a 100-kHz Ti:sapphire regenerative
      amplifier.
AB  - A 100-kHz mode-locked Ti:sapphire-seeded regenerative amplifier pumping an
      optical parametric amplifier generates femtosecond pulses tunable from 470 to 710
      nm. This output was compressed with a pair of prisms to bandwidth-limited pulses
      of 80- to 40-fs duration and more than 150 nJ of energy. These tunable pulses
      were then bandwidth expanded through self-phase modulation in bulk material and
      further compressed to less than 30-fs duration.

PMID- 19859271
TI  - Polarization-difference imaging: a biologically inspired technique for
      observation through scattering media.
AB  - Many animals have visual systems that exploit the polarization of light, and some
      of these systems are thought to compute difference signals in parallel from
      arrays of photoreceptors optimally tuned to orthogonal polarizations. We
      hypothesize that such polarization-difference systems can improve the visibility
      of objects in scattering media by serving as common-mode rejection amplifiers
      that reduce the effects of background scattering and amplify the signal from
      targets whose polarization-difference magnitude is distinct from the background.
      We present experimental results obtained with a target in a highly scattering
      medium, demonstrating that a manmade polarization-difference system can render
      readily visible surface features invisible to conventional imaging.

PMID- 19859273
TI  - Optoelectronic neural dendritic tree processing with electron-trapping materials.
AB  - We show that under simultaneous illumination of pulsed blue light and constant IR
      light the dynamic responses of electron-trapping materials could be employed to
      implement optically controlled neural dendritic responses. The importance of
      neurocomputing with biology-oriented spiking neurons and the role played by
      dendritic trees are discussed. Computer simulations of dendritic responses in
      biological neuron and experimental results of electron-trapping material dynamics
      are presented. These results show that electron-trapping materials are well
      suited for implementing optically controlled dendritic responses for use in large
      scale biology-oriented optoelectronic spiking neural networks.

PMID- 19859272
TI  - Gain and exposure scheduling to compensate for photorefractive neural-network
      weight decay.
AB  - A gain and exposure schedule that theoretically eliminates the effect of
      photorefractive weight decay for the general class of outer-product neural
      network learning algorithms (e.g., backpropagation, Widrow-Hoff, perceptron) is
      presented. This schedule compensates for photorefractive diffraction-efficiency
      decay by iteratively increasing the spatial-light-modulator transfer function
      gain and decreasing the weight-update exposure time. Simulation results for the
      scheduling procedure, as applied to backpropagation learning for the exclusive-OR
      problem, show improved learning performance compared with results for networks
      trained without scheduling.

PMID- 19859274
TI  - Planar optical configurations for crossover interconnects.
AB  - Two planar optics configurations for crossover interconnects are described, and
      the interconnection capacity of each configuration is derived on the basis of
      Gaussian beams' being relayed by microlens arrays. To reduce the optical path
      differences between bypass- and exchange-connection routes in the crossover
      configurations, we propose the use of two different substrates.

PMID- 19859275
TI  - Quadrature squeezing with ultrashort pulses in nonlinear-optical waveguides.
AB  - Using ultrashort laser pulses, we have observed quadrature squeezing and
      parametric gain in quasi-phase-matched KTiOPO(4) waveguides. Using a local
      oscillator pulse that is 2.5 times shorter than the squeezed pulse, we observed
      noise reduction of 12 +/- 1% below the shot-noise level. Parametric amplification
      and deamplification of a coherent seed pulse have also been observed, with no
      indication of gain-induced diffraction.

PMID- 19859276
TI  - Relationships between the complex degrees of coherence in the space-time and in
      the space-frequency domains.
AB  - A relationship is established between two correlation coefficients (complex
      degrees of coherence) frequently used in the theory of partially coherent optical
      fields. One of them characterizes correlation in the space-time domain, the other
      in the space-frequency domain. Some relations obtained previously by ad hoc
      methods are shown to readily follow from our general formula.

PMID- 19859278
TI  - Continuous-wave ultrasonic modulation of scattered laser light to image objects
      in turbid media.
AB  - Continuous-wave ultrasonic modulation of scattered laser light has been used to
      image objects in tissue-simulating turbid media for what is to our knowledge the
      first time. The ultrasound wave focused into the turbid media modulates the laser
      light passing through the ultrasonic focal zone. The modulated laser light
      collected by a photomultiplier tube reflects the local mechanical and optical
      properties in the focal zone. Buried objects are located with millimeter
      resolution by scanning and detecting alterations of the modulated optical signal.
      This technique has the potential to provide a noninvasive, nonionizing,
      inexpensive diagnostic tool for diseases such as breast cancer.

PMID- 19859281
TI  - Injection-seeded alexandrite ring laser: performance and application in a water
      vapor differential absorption lidar.
AB  - A new laser system for use of differential absorption lidar (DIAL) in
      measurements of tropospheric water vapor and temperature is introduced. This
      system operates in the 720-780-nm region and is configured as an alexandrite ring
      laser injection seeded by a cw Ti:sapphire ring laser. This combination provides
      for the necessary narrow-bandwidth, high-frequency stability and excellent
      spectral purity. A bandwidth of <5.0 x 10(-3) cm(-1), a frequency stability of
      2.1 x 10(-3) cm(-1) rms, and a spectral purity of 99.995% at 726 nm have been
      achieved during extended periods of operation. A comparison of a DIAL water-vapor
      measurement with a radiosonde in the boundary layer between 500 and 2000 m was
      performed. The maximum deviation between the humidity profiles is 15%, the
      standard deviation 1.6%, and the difference between the mean values 1%.

PMID- 19859283
TI  - Variable optical delay line based on a birefringent planar optical platform.
AB  - A variable optical delay line is proposed for accurately adjusting optical signal
      timing in photonic systems. This delay line is based on a birefringent planar
      optical platform characterized by the multiple reflection of light beams. It
      consists of a birefringent plate, lambda/4 plates, mirrors, and a liquid-crystal
      layer. It can select an arbitrary delay from a set of discrete delays precisely
      determined by the thickness of the birefringent plate. A feasibility study
      confirms seven-step delay line operation with a 240-ps unit delay.

PMID- 19859279
TI  - Laser picosecond acoustics in double-layer transparent films.
AB  - By the optical pump-and-probe technique, picosecond acoustic pulses are excited
      and detected in thin transparent double-layer films of silica and silicon nitride
      upon opaque chromium substrates. By taking both acoustic and optical multiple
      reflections into account, one can successfully model the main features of the
      reflectance variation. The film thicknesses, sound velocities, and photoelastic
      constants are derived by use of known values of the refractive indices.

PMID- 19859280
TI  - Adjustable phase control in stabilized interferometry.
AB  - We report an optoelectronic feedback loop that permits the active stabilization
      of an interferometric setup for any chosen value of the phase between the
      interfering beams. This method is based on phase modulation and homodyne
      detection techniques. The phase can be stabilized with a precision of better than
      1 deg for our experimental conditions.

PMID- 19859277
TI  - Real-time resonant holography using bacteriorhodopsin thin films.
AB  - We demonstrate real-time, two-dimensional measurement of species concentration in
      a turbulent flow field. The dynamics of pulsed holographic recording and decay
      are characterized for a 46-microm polymer film containing bacteriorhodopsin. We
      produced species-specific holographic interferograms of sodium vapor by
      simultaneously recording two holograms at different wavelengths, one tuned near a
      sodium absorption feature and the other tuned off resonance. An analysis of the
      techniques' sensitivity is presented.

PMID- 19859282
TI  - Photonic sampler for 1550-nm signals.
AB  - A device that extracts a sample of configurable length from a 1550-nm
      communication signal under the command of a pulsed light beam is presented. The
      device is realized by means of two CdTe:In optical switches; it has 10-ns rise
      and fall times and a sampling window of the duration of a microsecond. The
      photonic sampler is fully transparent to the optical communication signals in the
      third window.

PMID- 19859284
TI  - Numerical analysis of the optimal length and profile of a linearly chirped fiber
      Bragg grating for dispersion compensation.
AB  - We propose a theoretical investigation of the length and coupling profile of a
      linearly chirped fiber Bragg grating for maximum dispersion compensation in a
      repeaterless optical communication system. The system consists of 100 km of
      standard optical fiber in which a 1550-nm signal, directly modulated at 2.5
      Gbits/s, is launched. We discuss the results obtained with 6-, 4.33-, and 1-cm
      long linearly chirped fiber Bragg gratings having Gaussian and uniform coupling
      profiles. We numerically show that a 4.33-cm-long chirped fiber Bragg grating
      having a uniform coupling profile is capable of compensating efficiently for the
      dispersion of our optical communication system.

PMID- 19859285
TI  - Parametric characterization of the phase at the far field.
AB  - By use of the intensity moment formalism, a new tridimensional beam parameter is
      defined that is rotationally invariant and remains constant under propagation
      through certain classes of first-order optical systems. The special case of
      rotationally symmetric beams is considered in some detail. Also, for coherent
      beams this parameter is shown to be closely connected to the quadratic form of
      the phase of the directional power spectrum.

PMID- 19859288
TI  - Time-resolved spatial parametric characterization of pulsed light beams.
AB  - New time-resolved spatial parameters are given that characterize the behavior of
      pulsed beams along with their propagation laws through first-order optical
      systems. The analytical conditions that should be fulfilled so that the intensity
      moment formalism remains valid are investigated. Their physical meaning is also
      discussed, along with the implications for the evolution of the spatial profile
      of a pulsed beam.

PMID- 19859289
TI  - Measurements of the modal properties of a diffractive-optic graded-phase
      resonator.
AB  - We measured the higher-order modes of a diffractive-optic graded-phase resonator
      by suppressing the lower-order modes of a flash-lamp-pumped Nd:YAG laser with
      spatial filters. A diffractive-optic end mirror was used to establish a flattop
      fundamental mode. Measurements of the fundamental and higher-order mode shapes
      agreed with theoretical models. Quantitative measurements of modal discrimination
      substantiate the predictions of large discrimination between the fundamental and
      second-order modes.

PMID- 19859286
TI  - Excitation of resonances of microspheres on an optical fiber.
AB  - Morphology-dependent resonances (MDR's) of solid microspheres are excited by
      using an optical fiber coupler. The narrowest measured MDR linewidths are limited
      by the excitation laser linewidth (<0.025 nm). Only MDR's, with an on-resonance
      to off-resonance intensity ratio of 10(4), contribute to scattering. The
      intensity of various resonance orders is understood by the localization principle
      and the recently developed generalized Lorentz-Mie theory. The microsphere fiber
      system has potential for becoming a building block in dispersive microphotonics.
      The basic physics underlying our approach may be considered a harbinger for the
      coupling of active photonic microstructures such as microdisk lasers.

PMID- 19859287
TI  - Scattering by one-dimensional random rough metallic surfaces in a conical
      configuration.
AB  - We present experimental results on the angular distribution of the light
      scattered by a one-dimensional goldcoated randomly rough surface in a conical
      configuration. The term conical refers to the case in which the plane of
      incidence makes an oblique angle with respect to the generators of the surface.
      The surface profile of our sample constitutes a good approximation to a Gaussian
      random process with a Gaussian correlation function. Effects related to the
      phenomenon of enhanced backscattering are observed.

PMID- 19859291
TI  - Derivation of phase in computer-aided photoelasticity.
AB  - Phase-shifting techniques have been successfully implemented to yield the phase
      from sinusoidally modulated intensity fields in interferometry. However, when the
      intensity fields are that of squared sinusoidal modulation, as in the case of
      photoelasticity, implementation of existing phase-shift operations will result in
      error. An operation is outlined to derive faultlessly the phase in computer-aided
      photoelasticity.

PMID- 19859292
TI  - Supermirror phase anisotropy measurement.
AB  - The high sensitivity of the eigenstates of a large-finesse passive Fabry-Perot
      cavity is used to measure the residual anisotropy of supermirrors at strictly
      normal incidence. An experimental demonstration leads to the measurement of phase
      retardances of the order of 10(-6) rad.

PMID- 19859293
TI  - Second-harmonic generation in Bragg-resonant quasi-phase-matched periodically
      segmented waveguides.
AB  - Second-harmonic generation in Bragg-resonant quasi-phase-matched periodically
      segmented waveguides is studied experimentally and theoretically. At resonance, a
      deep spectral valley appears in the quasi-phase-matching curve. Nevertheless, in
      practice, the conversion efficiency is significant, in spite of this effect,
      because of reduced reflections, especially at 2omega. The mechanism behind this
      reduction seems to be small random variation in the location and shape of the
      domain boundaries.

PMID- 19859294
TI  - Mutually pumped phase-conjugate mirror: fish-head configuration.
AB  - A new mutually pumped phase-conjugate mirror configuration is demonstrated in
      barium titanate crystals, in which the beams travel in a geometrical path similar
      to the outline of a fish's head. This configuration has a fast (~1-s) response
      time, for input beam powers of 56 mW, after which a stable phase-conjugate
      reflectivity of ~28% is attained. The tolerance of the output to both angular and
      positional misalignment is assessed. Two detailed images were simultaneously
      phase conjugated, and it was found that 125-microm features could be clearly
      resolved without cross talk. We tentatively suggest possible mechanisms for this
      configuration.

PMID- 19859297
TI  - Mirrorless self-pumped phase conjugation in KNbO(3):Mn and KNbO(3):Co.
AB  - Self-pumped phase conjugation is experimentally studied in the usual 0 degrees 
      cut potassium niobate crystals doped with either manganese or cobalt. Phase
      conjugate reflectivities as high as 52% and 32% are obtained for these two kinds
      of crystal in the mirrorless cat configuration at 488 nm. The influence of
      experimental conditions, such as the incidence angle, the incident position, and
      the incident intensity, on phase conjugation are studied.

PMID- 19859295
TI  - High-repetition-rate femtosecond optical parametric oscillator based on KNbO(3).
AB  - A Ti:sapphire-pumped, high-repetition-rate, femtosecond optical parametric
      oscillator based on potassium niobate is described. Signal pulses as short as 90
      fs have been recorded, and idler pulses as short as 105 fs have been measured.
      Tuning from 1.2 to 1.4 microm in the signal branch and from 1.76 to 2.2 microm in
      the idler branch has been achieved. Output powers as high as 300 mW have been
      measured at the signal wavelength.

PMID- 19859296
TI  - Comparison of photorefractive-index changes in annealed-proton-exchanged channel
      waveguides in MgO-doped and congruent LiNbO(3).
AB  - A quantitative comparison of the photorefractive effect in annealed proton
      exchanged channel waveguides in MgO-doped and congruent LiNbO(3) at the
      wavelengths of 633 and 830 nm is presented. An accurate measurement technique is
      described to measure the refractive-index change as a function of time and the
      guided mode intensity for different wavelengths. The results show that doping
      with 7% MgO reduces the photorefractive effect at a wavelength of lambda = 633 nm
      by 2 orders of magnitude. The photorefractive effect in the doped substrate shows
      only a weak dependence on the guided power. Doping with 4 mol.% MgO has only
      little effect on the photorefractive effect compared with that on the congruent
      material. A reduced photovoltaic current is responsible for the small
      photorefractive effect in the 7 mol. %-doped substrate.

PMID- 19859300
TI  - Ultrashort-pulse generation in degenerate optical parametric oscillators.
AB  - Solitary-pulse generation in a degenerate optical parametric oscillator subjected
      to continuous-wave pumping is investigated theoretically. As with solitary
      lasers, pulse shaping is a phase effect induced by the interplay between self
      phase modulation and group-delay dispersion, but pulse stability is ensured by
      the parametric gain itself and does not require any fast saturable absorber
      action.

PMID- 19859303
TI  - Soliton singularity in the system with nonlinear gain.
AB  - Solitons propagating in a system with spectral filtering, being nonlinearly
      stable, suffer from the growth of linear radiation. This effect can be partially
      overcome by the use of nonlinear gain. I analyze steady-state soliton propagation
      in such a system and reveal unexpected the singularity of the soliton amplitude.

PMID- 19859298
TI  - Incoherent enhancement of the photorefractive response in Bi(12)SiO(20) by
      subharmonic interaction.
AB  - A new mechanism for enhancing the photorefractive grating amplitude in
      Bi(12)SiO(20) is presented. We show experimentally that, by recording two
      photorefractive running gratings induced by two pairs of mutually incoherent
      laser beams, it is possible for the two gratings to transfer energy from one to
      the other. As might be expected, maximum energy transfer is obtained when the
      phase velocities of the two gratings are equal.

PMID- 19859290
TI  - Binary gratings as beam splitters with asymmetric signals.
AB  - In the framework of scalar diffraction theory, binary digital holograms and
      Dammann gratings generate symmetric intensity distributions as diffraction
      patterns. If asymmetric signals are of interest, either an offset from the
      optical axis has to be introduced or more quantization levels have to be used. We
      show that a synthesis on the basis of rigorous diffraction theory permits binary
      elements with subwavelength features to realize on-axis asymmetric signals.

PMID- 19859304
TI  - Wet-chemical fabrication of a single leakage-channel grating coupler.
AB  - We demonstrate the fabrication of a unique optical device, the single leakage
      channel grating coupler, using solgel techniques. Design specifications are
      outlined to establish the material criteria for the sol-gel compositions.
      Material choice and preparation are described. We evaluate the characteristics
      and performance of the single leakage-channel grating coupler by comparing the
      predicted and the measured branching ratios. The branching ratio of the solution
      derived device is within 3% of the theoretically predicted value.

PMID- 19859299
TI  - Response of a Brillouin amplifier and four-wave mixing mirror to a spectrally
      broadened signal beam.
AB  - We show that, when the input signal to a Brillouin amplifier and a phase
      conjugate mirror is spectrally broadened, the Brillouin interaction can still
      efficiently amplify and conjugate the input.

PMID- 19859301
TI  - All-optical switching in two cascaded nonlinear directional couplers.
AB  - We report on what is to our knowledge the first demonstration of all-optical
      switching in two integrated nonlinear directional couplers cascaded together in
      series. The directional couplers were fabricated from AlGaAs and operated at a
      wavelength of 1.53 microm, which corresponded to the half-band gap. The two
      devices were fabricated on the same chip, thereby eliminating coupling and
      reflection losses. We also report on the effects of pulse breakup.

PMID- 19859302
TI  - Methods of constructing a long-haul soliton transmission system with fibers
      having a distribution in dispersion.
AB  - We present methods for minimizing error in soliton transmission systems
      consisting of fibers having a distribution in dispersion, D.

PMID- 19859305
TI  - Self-seeding in a dual-cavity-type pulsed Ti:sapphire laser oscillator.
AB  - We have constructed a self-seeded Ti:sapphire laser oscillator by using a dual
      cavity configuration that consists of a Littman configuration cavity and a
      partially reflecting feedback mirror. This configuration can be decomposed with
      two kinds of cavity, a grazing-incidence cavity and a standing-wave cavity. The
      former behaves as an injection seeder and the latter as a slave oscillator. This
      Ti:sapphire laser system is capable of delivering a continuously tunable laser
      pulse with a narrow linewidth. Injection at the laser emission region of the free
      running Ti:sapphire laser resulted in essentially complete energy extraction.

PMID- 19859307
TI  - Coupled-cavity electro-optically Q-switched Nd:YVO(4) microchip lasers.
AB  - Nd:YVO(4) microchip lasers have been electro-optically Q switched to produce 12
      microJ pulses of 115-ps duration at repetition rates of up to 1 kHz. At a
      repetition rate of 2.25 MHz, 0.16-microJ pulses with an 8.8-ns duration were
      obtained.

PMID- 19859306
TI  - Multiwatt diode-pumped Yb:YAG thin disk laser continuously tunable between 1018
      and 1053 nm.
AB  - A new powerful source of broadly (35-nm) tunable laser radiation in the near
      infrared (near 1030 nm) wavelength range is presented. Inserting a birefringent
      filter into a 10-W diode-pumped Yb:YAG thin disk laser resonator gives several
      watts of narrow-linewidth (0.07-nm) continuously tunable cw output power. By
      taking advantage of the power scalability of the thin disk concept, even hundreds
      of watts of tunable power with near-diffraction-limited beam quality and high
      efficiency are feasible. Generation and amplification of subpicosecond pulses
      with high average and peak powers are also promising applications of the Yb:YAG
      thin disk laser.

PMID- 19859308
TI  - Quenching of neodymium fluorescence by molecular hydrogen.
AB  - We show that the hydrogen-loading technique used to enhance a fiber's ultraviolet
      photosensitivity for writing Bragg gratings can lead to quenching of the lasing
      ion's fluorescence. The neodymium fluorescence and radiative lifetimes are
      measured for the untreated fiber, the hydrogen-loaded fiber, and the postannealed
      fiber. We show that postannealing can be used to remove the unreacted hydrogen
      molecules from the fiber laser and restore the radiative lifetime to near that of
      its original value.

PMID- 19859309
TI  - Doubly resonant optical parametric oscillator formed by index matching cavity
      mirrors directly onto an uncoated LiB(3)O(5) crystal.
AB  - We demonstrate the use of index-matching fluid to contact cavity mirrors directly
      onto an uncoated LiB(3)O(5) crystal to form a compact, stable resonator for use
      as an optical parametric oscillator. Specifically, we report on the
      characteristics of a continuous-wave, doubly resonant, type II phase-matched
      LiB(3)O(5) optical parametric oscillator formed in this way. Using a single
      frequency argon-ion pumping laser operating at 514.5 nm, we measured a pump power
      threshold of approximately 100 mW and a total external conversion efficiency of
      approximately 15%. By altering the crystal temperature under noncritical phase
      matching, we measured coarse frequency tuning over approximately 36 THz, limited
      only by mirror coating bandwidths. We discuss also the transverse and
      longitudinal mode properties of the optical parametric oscillator outputs.

PMID- 19859310
TI  - Targeting periodic oscillations of external cavity laser diodes.
AB  - A simple method of targeting periodic dynamics appearing in semiconductor lasers
      subject to optical feedback is demonstrated. Possible applications of the
      technique in chaotic communications are identified, and its advantages for chaos
      control are discussed.

PMID- 19859311
TI  - Observation of dynamic wavelength shifts of a four-beam laser diode and study of
      its adaptability to optical heads.
AB  - Dynamic wavelength shifts for a four-beam laser diode were observed with a streak
      camera system. The wavelength shift does not exceed 2 nm for pulsed laser beam
      operation at a bottom power of 5 mW and a peak power of 40 mW. For a 5-mW
      continuous operation laser beam, the induced wavelength shift in the presence of
      another laser beam under the above pulse condition does not exceed 1 nm. The
      observed wavelength shifts are small enough for practical use, and this four-beam
      laser diode can be successfully applied to multibeam optical heads for parallel
      data processing.

PMID- 19859312
TI  - Coherence-collapsed 1.3-microm multimode laser diode for the fiber-optic
      gyroscope.
AB  - Coherence-collapsing feedback applied to a 1.3-microm multimode laser diode is
      shown to sufficiently decouple the longitudinal modes and broaden their linewidth
      that the laser becomes suitable for use in a low-drift depolarized fiber-optic
      gyroscope.

PMID- 19859314
TI  - Pulse characteristics of passively mode-locked diode lasers.
AB  - For the first time to our knowledge, asymmetric pulse shapes and the linear and
      nonlinear chirp from a passively mode-locked semiconductor laser are directly
      measured. For the laser tuned to various center wavelengths, fall-time-to-rise
      time ratios of 2.0 to 2.5 are measured. With the laser tuned to the shorter
      wavelength side of its tuning range, a significant quadratic chirp of -60
      fs/nm(2) is measured, along with a linear chirp of -800 fs/nm. The nonlinear
      chirp is responsible for the asymmetrically shaped compressed pulses that produce
      long-tailed autocorrelations.

PMID- 19859313
TI  - Long-term stable mode locking of a visible diode laser with phase-conjugate
      feedback.
AB  - We present a new method to obtain long-term stable phase-conjugate feedback (pcf)
      with a photorefractive crystal for a mode-locked semiconductor laser. The phase
      conjugate mirror is a barium titanate crystal in a self-pumped internal
      reflection configuration, and the laser is a visible, antireflection-coated
      AlGaInP diode. We describe a new dynamic writing procedure for growth of an index
      grating in the photorefractive crystal that leads to stable pcf and discuss the
      reasons for this stability, which is the major advantage of this method over
      previously reported ones. Using this superior method, we achieve stable mode
      locked operation of the laser with pulse widths of ~30 ps and a timing jitter of
      less than 2 ps.

PMID- 19859315
TI  - Time-domain images.
AB  - We demonstrate that, using a hologram, we can convert a spatial x-y image into an
      x-t image, where one spatial dimension is now transformed into the time domain.
      In particular, we generate the temporal equivalent of our corporate logo, where
      every pixel of the image is now represented by a short optical pulse.

PMID- 19859316
TI  - Ultrashort optical waveform measurements using frequency-resolved optical gating.
AB  - We measure the intensity and phase of ultrashort pulses from a self-mode-locked
      Ti:sapphire laser using the recently developed technique of frequency-resolved
      optical gating. These results represent to our knowledge the shortest complete
      optical waveform characterization measurements performed to date. We also verify
      recent theoretical calculations that predict that the main limitation on the
      pulse duration from these lasers is the presence of uncompensated higher-order
      dispersion.

PMID- 19859317
TI  - Self-starting mode locking of a cw Nd:YAG laser using cascaded second-order
      nonlinearities.
AB  - The nonlinear mode variations induced by the equivalent third-order
      susceptibility resulting from cascaded secondorder nonlinearities in an
      intracavity lithium triborate crystal are exploited for mode locking of a cw
      Nd:YAG laser. The loss modulations are provided by a slit, as in the Kerr-lens
      mode-locking scheme. The mode-locking process is self-starting and produces
      nearly transform-limited pulses of 14-ps duration with 0.5-W average power.

PMID- 19859319
TI  - Quantized phase optimization of two-dimensional Fourier kinoforms by a genetic
      algorithm.
AB  - We have developed a phase optimization method of a quantized kinoform by a
      genetic algorithm. Because the genetic algorithm inherently deals with discrete
      values, the quantized phase of the kinoform can be easily estimated. The two
      dimensional Fourier kinoform can utilize effectively the periodicity of the
      discrete Fourier transform in the genetic algorithm. This condition enables us to
      perform the crossover process that is one of the processes in genetic algorithm
      without a spatial bandwidth of the kinoform. The optimization has been performed
      successfully in computer simulation. The optically reconstructed image agrees
      well with the theoretical one.

PMID- 19859321
TI  - Selective imaging with a frequency-modulated laser-diode interferometer.
AB  - It is shown that selective extraction of an image from multiple interferograms
      can be performed by electronic processing of interference beat signals. The
      frequencies of beat signals generated by ramping the laser-diode (LD) current are
      proportional to the optical path differences between the reference and the object
      arms in a LD interferometer. A beat signal with a frequency corresponding to an
      object-assigned interferometric arm can be extracted by electronic tuning. An
      interference pattern detected by a dissector camera is sampled in synchronism
      with the beat signal, which permits two-dimensional selective imaging.

PMID- 19859323
TI  - Optical image encryption based on input plane and Fourier plane random encoding.
AB  - We propose a new optical encoding method of images for security applications. The
      encoded image is obtained by random-phase encoding in both the input and the
      Fourier planes. We analyze the statistical properties of this technique and show
      that the encoding converts the input signal to stationary white noise and that
      the reconstruction method is robust.

PMID- 19859320
TI  - Multiple-error-correcting codes for improving the performance of optical matrix
      vector processors.
AB  - I examine the use of Reed-Solomon multiple-error-correcting codes for enhancing
      the performance of optical matrix-vector processors. An optimal code rate of 0.75
      is found, and n = 127 block-length codes are seen to increase the optical matrix
      dimension achievable by a factor of 2.0 for a required system bit-error rate of
      10(-15). The optimal codes required for various matrix dimensions are determined.
      I show that single code word implementations are more efficient than those
      utilizing multiple code words.

PMID- 19859318
TI  - Terabit speed retrieval of femtosecond accumulated photon echoes.
AB  - An accumulated photon echo readout speed as fast as 27 Tbits/s was demonstrated
      by a new single-shot cross-correlation method for a femtosecond four-pulse packet
      stored by spectral hole burning in an octaethylporphine-doped polystyrene sample.

PMID- 19859322
TI  - Distributed phase plates for super-Gaussian focal-plane irradiance profiles.
AB  - The design of phase plates based on a phase-retrieval algorithm has been shown to
      be successful in achieving high order super-Gaussian distributions in the far
      field; however, these phase plates exhibit wide-angle scattering losses due to
      phase discontinuities. We report that, by starting with a distributed phase plate
      that is a strictly continuous surface and using only a few cycles of a phase
      retrieval algorithm, we have obtained good fourth-order super-Gaussian fit and
      lower scattering loss.

PMID- 19859325
TI  - Aerosol particle microphotography and glare-spot absorption spectroscopy.
AB  - The relative intensities of glare spots in the image of an electrodynamically
      trapped aerosol droplet are measured experimentally with an aerosol particle
      microscope and calculated theoretically. The theoretical calculations are in good
      agreement with these experiments and indicate that the intensities of these spots
      are extremely sensitive to the imaginary part of the refractive index.
      Experimentally, we obtain the molecular absorption spectrum of an impurity within
      a droplet by recording the spectrum of an individual glare spot produced by
      broadband illumination.

PMID- 19859329
TI  - White-light scanning fiber Michelson interferometer for absolute position
      distance measurement.
AB  - A white-light fiber interferometer working in the spatial domain, using two fiber
      ends in a hollow tube as the sensing head and an electric magnetic actuator
      mirror reflector as the path-compensation-measurement element, is presented.
      Analysis and preliminary experiments have demonstrated a repeatability of 0.5
      microm (2sigma) for position-distance measurement, and the measurement
      uncertainty was estimated to be 1.5 microm (2sigma) over a distance range of 150
      microm. Suggestions for further improving the measurement accuracy and response
      speed are also given.

PMID- 19859324
TI  - Observation of cavity quantum-electrodynamic effects in a Nd:glass microsphere.
AB  - In a Nd:glass microspherical cavity the enhancement and inhibition of spontaneous
      emission processes that are due to cavity QED effects have been observed. The
      rates of the enhanced spontaneous emission are location dependent and reach a
      maximum value of more than 10(3) times the free-space value. The large
      enhancement strongly modifies the decay processes of Nd ions in glass, and the
      radiative properties of Nd:glass have been changed. As a result a new spectrum
      including new lasing wavelengths in the Nd:glass sphere has been observed.

PMID- 19859326
TI  - Optimization of a three-dimensional object composite Fourier hologram.
AB  - It was found that the optimum subhologram dimension of the composite Fourier
      transform hologram for minimizing image blur depends on object depth and
      information reduction ratio. Optimization of the subhologram dimension permits us
      to calculate the parameters of the composite Fourier-transform hologram for its
      applications to hologram transmission systems and to electroholographic three
      dimensional displays.

PMID- 19859327
TI  - Statistical analysis of cross-talk noise and storage capacity in volume
      holographic memory: image plane holograms.
AB  - We investigate the cross-talk noise in optical storage based on angle-multiplexed
      image plane volume holograms. Simple expressions for the signal-to-noise ratio
      and the storage density are obtained. The cross-talk noise is found to limit the
      size of the pixels and the number of recorded holograms. The cross-talk-limited
      storage density of image plane holographic storage is found to be close to that
      of Fourier plane holographic storage.

PMID- 19859328
TI  - Holographic storage using shift multiplexing.
AB  - We demonstrate theoretically and experimentally a new multiplexing method for
      volume holographic storage using a single reference beam that is composed of
      multiple plane waves or is a spherical wave. We multiplex the holograms by
      shifting the recording material or the recording/readout head. The volume
      properties of the recording medium allow selective readout of holograms stored in
      successive overlapping locations. High storage densities can be achieved with a
      relatively simple implementation by use of the new method.

PMID- 19859330
TI  - Group-delay measurement on laser mirrors by spectrally resolved white-light
      interferometry.
AB  - The frequency-dependent group delay of dielectric mirrors was measured by
      spectrally resolved white-light interferometry. Chirped mirrors and thin-film
      Gires-Tournois interferometers designed for dispersion control in a femtosecond
      Ti:sapphire laser oscillator-amplifier system were tested with a group-delay
      resolution of +/-0.2 fs and a spectral resolution of ~1 nm over the spectral
      range of 670-870 nm.

PMID- 19859331
TI  - Intracavity technique for improved Raman/ Rayleigh imaging in flames.
AB  - A novel intracavity laser diagnostic has been developed to perform quantitative
      two-dimensional imaging of major species and temperature by using spontaneous
      Raman scattering and Rayleigh scattering in a turbulent flame. A flash-lamp
      pumped dye laser cavity is modified to include sheet-forming optics and 100%
      reflecting end mirrors. In a comparison of this system with a laser configuration
      with the sheet-forming optics outside the cavity, the beam waist is comparable,
      while the intensity is increased by a factor of 5. This technique has
      applicability to many systems in which weak scattering must be monitored, such as
      Rayleigh scattering, Raman scattering, and laser-induced fluorescence of certain
      combustion radicals.

PMID- 19859333
TI  - Five-channel surface-normal wavelength-division demultiplexer using substrate
      guided waves in conjunction with a polymer-based Littrow hologram.
AB  - We report on a five-channel wavelength-division demultiplexer using substrate
      guided waves in conjunction with a polymer-based Littrow hologram operating at
      700, 710, 720, 730, and 740 nm. An average cross talk of -40 dB between adjacent
      channels is measured. Diffraction efficiencies of 69%, 78%, 83%, 77%, and 69% are
      both experimentally and theoretically confirmed for the five-channel device. We
      also present further study aimed at reducing the wavelength channel separation to
      1 nm and find that achieving such a goal requires a device length of 6.4 cm
      corresponding to a propagation distance of 9.05 cm.

PMID- 19859336
TI  - Radiation patterns from lens-coupled terahertz antennas.
AB  - We report on investigations of the angular distribution of the radiation emitted
      from a terahertz antenna system equipped with a truncated spherical silicon lens.
      The pattern is calculated by wide-angle interference principles and Huygens
      Fresnel diffraction theory. Experimental determination of the radiation pattern
      is performed by spatially resolved terahertz time-domain spectroscopy. Good
      agreement between theory and experiment is obtained, and we find that the
      terahertz beam can be represented by a Gaussian beam emitted from a circular
      aperture equal to the diameter of the lens.

PMID- 19859332
TI  - Distributed optical-fiber sensing by four-photon mixing pulse walk-off.
AB  - We propose a distributed optical-fiber sensing scheme using four-photon mixing
      pulse walk-off. We use a copropagating system in which only a pump wave is
      launched into the fiber. We analyze the performance by including the effects of
      fiber birefringence, group-velocity dispersion, and self-phase modulation. A
      short system with high sensitivity and good resolution can be built. The useful
      operating length is limited by self-phase-modulation-induced pulse broadening.

PMID- 19859335
TI  - Rigorous analysis of power transfer in grating-assisted couplers.
AB  - The fields guided by planar gratings embedded in dielectric layers are amenable
      to exact analytical solutions if the grating profile is rectangular. Such a
      solution reveals that power transfer in grating-assisted couplers is optimized if
      the couplers are designed to operate at a point that does not necessarily satisfy
      phase-matching conditions.

PMID- 19859334
TI  - Improved polarizer in the infrared: two wire-grid polarizers in tandem.
AB  - A widely used polarizer in the IR is the wire-grid polarizer. Wire-grid
      polarizers with a typical minimal wire spacing of ~0.25 microm perform well in
      the middle IR and the far IR, but in the near IR the performance deteriorates as
      the wavelength approaches the wire spacing. A possibility for improving this
      performance is to put two wire grids in tandem with their transmission axes
      parallel. Starting with the extended Mueller matrix description for a single wire
      grid, we present a mathematical treatment of this tandem polarizer showing that
      performance improves quadratically; e.g., a single polarizer extinction ratio of
      100 increases to a tandem extinction of 10,000. The improved performance is also
      verified experimentally.

PMID- 19859340
TI  - High-frequency resonances in photorefractive crystals.
AB  - Two-wave mixing in photorefractive materials is investigated for the case of
      applied dc electric fields and large detuning frequencies and for high-frequency
      alternating electric fields. The appearance of high-frequency resonances is
      demonstrated.

PMID- 19859337
TI  - Simple algorithm for reconstructing fiber gratings from reflectometric data.
AB  - A simple, fast, and accurate algorithm is presented that is suitable for
      retrieving spatial grating structures in single-mode waveguides from
      reflectometric data. In particular, it is tailored to coherence-domain
      reflectometric measurements. Since the scheme uses a physical/experimental line
      of reasoning and the standard mathematics of communication theory, it is easy to
      survey and may also yield a simplified access to generalized problems not covered
      by the common coupled-mode equations.

PMID- 19859341
TI  - Ultrabroad-bandwidth multifrequency Raman soliton pulse trains.
AB  - I have discovered that in the coherent regime of ultrabroad-bandwidth Raman
      generation, a large number of long-lived soliton pulse trains are spontaneously
      generated. This novel solution of the dispersionless and highly transient regime,
      involving more than 40 distinct Raman lines of comparable amplitude, is found to
      be a strong attractor in the nonlinear dynamics, even when the system is
      initially far from this limit.

PMID- 19859338
TI  - Eroded monomode optical fiber for whispering-gallery mode excitation in fused
      silica microspheres.
AB  - We demonstrate the efficient excitation of high-Q whispering-gallery modes in
      near-spherical fused-silica microparticles in the size range 60-450 microm by the
      use of an eroded monomode optical fiber. When the sphere is placed in the
      evanescent field of the guided fiber mode, light is resonantly coupled from the
      fiber into the microparticle. We report a broadening of resonance modes and a
      shift of the resonance central frequency as the coupling strength is increased by
      reduction of the gap between the sphere and the fiber.

PMID- 19859343
TI  - Transverse modulational instabilities in the presence of stimulated rotational
      Raman scattering with a high-energy laser.
AB  - Transverse modulational instabilities have been observed in two high-energy laser
      experiments. In one experiment a collimated laser beam with a 351-nm wavelength
      propagated through air and generated stimulated rotational Raman scattering. In
      the second experiment a 1-kJ laser pulse with a 1054-nm wavelength was focused
      into a spatial filter having a 50-microm residual pressure. In both experiments
      the transverse modulational instability took the form of a hexagonal emission
      pattern in the interaction region. The instability can be understood from an
      analysis in the plane-wave approximation.

PMID- 19859339
TI  - Phase-shift interference microscope for the investigation of dipole-orientation
      distributions.
AB  - A compact experimental setup for an electro-optical microscope is introduced. The
      microscope is based on phase-shift interferometry (a well-known tool for surface
      profilometry) that is modified for measuring electrooptic responses. Its
      feasibility is demonstrated with a two-dimensional map of the electro-optic
      activity of a periodically poled nonlinear-optical side-chain polymer.

PMID- 19859344
TI  - Generation of high-contrast narrow-band subpicosecond correlations from broadband
      stochastic fields.
AB  - We demonstrate that two broadband stochastic fields generated by use of either
      parametric frequency conversion or stimulated Raman scattering can be mixed in a
      nonlinear crystal to produce an output spectrum with a pronounced narrow-band
      feature. This narrow-band feature, which we show is due to the phase-correlated
      nature of the beams, is present when the two broadband beams are delayed less
      than a coherence length relative to each other. We apply this technique to a
      novel measurement of the field cross-correlation function between two broadband
      stochastic fields with different center frequencies.

PMID- 19859345
TI  - Dark solitons in dispersive quadratic media.
AB  - We analyze dark solitons supported by second-order parametric interactions
      between the fundamental and second harmonics in the presence of dispersion and
      group-velocity mismatch. We reveal various types of solitary waves, including a
      family of two-wave dark solitons propagating on a modulationally stable
      background, dark solitons with nonmonotonic tails, and bound states of dark
      solitons.

PMID- 19859346
TI  - Nonstationary self-focusing in photorefractive media.
AB  - We consider nonstationary self-focusing of an optical beam propagating in a
      photorefractive medium in the framework of a two-dimensional model.

PMID- 19859348
TI  - Blue-light generation by quasi-phase-matched frequency doubling in thermally
      poled optical fibers.
AB  - Periodically patterned second-order nonlinearities are created in optical fibers
      by thermal poling in vacuo. Cw quasi-phase-matched frequency conversion to the
      blue is demonstrated. The measured bandwidth, 0.78 nm cm, is close to the
      theoretical prediction.

PMID- 19859342
TI  - Astigmatism and gain guiding in Kerr-lens mode-locked lasers.
AB  - The effects of astigmatism and the radial variation of the gain on Kerr-lens mode
      locking (KLM) are studied with the help of an extended ABCD matrix formalism. A
      dramatic broadening of the allowed cavity parameter region is predicted that
      permits KLM in almost the whole stability region. The cavity design for KLM with
      an aperture differs significantly from the design for KLM without an aperture,
      because of the saturable diffraction loss.

PMID- 19859347
TI  - Generation of 90-mW continuous-wave tunable laser light at 280 nm by frequency
      doubling in a KDP crystal.
AB  - Laser light at a wavelength of 560 nm from a commercial ring dye laser has been
      frequency doubled in an external enhancement cavity with a KDP crystal. The
      cavity employs a new design consisting of only three mirrors, permitting a
      shorter cavity length as well as compensation for astigmatism and coma. With an
      input power of ~950 mW of green light, ~90 mW of UV light has been produced. The
      wavelength of the UV light can be tuned corresponding to +/-3 nm by angle tuning
      of the crystal, and the optical frequency can be scanned electronically up to +/
      10 GHz.

PMID- 19859349
TI  - Nonexistence of the optical Faraday effect.
AB  - It is experimentally shown that the optical Faraday effect associated with a
      circularly polarized light beam and predicted by Evans [J. Mol. Liq. 55, 127
      (1993)] does not exist.

PMID- 19859350
TI  - Injection seeding for the enhancement of high-order anti-Stokes stimulated Raman
      scattering.
AB  - We have investigated the effects of Stokes and anti-Stokes pulse injection on
      high-order anti-Stokes Raman scattering for efficient generation of vacuum
      ultraviolet radiation. The output energies as well as the spatial profiles of
      anti-Stokes pulses were much improved by injection. Enhancement factors increased
      for higher orders of anti-Stokes pulses. The shift of optimum pressure together
      with the change of profile from a ring to a Gaussian-like shape induced by
      injection indicates that the enhancement is due to the modification of phase
      matching geometry in four-wave Raman mixing for anti-Stokes generation.

PMID- 19859353
TI  - Control of optical solitons by light waves.
AB  - A new method of controlling optical solitons by means of light wave(s) in fibers
      is presented. By a proper choice of light wave(s), parametric four-wave mixing
      can control the soliton shape as well as the soliton parameters (amplitude,
      frequency, velocity, and position).

PMID- 19859352
TI  - Second-harmonic-generation-induced optical bistability in prism or grating
      couplers.
AB  - We deal with second-harmonic generation in chi((2)) nonlinear-optical resonators
      such as prism or grating couplers. The theoretical study is performed within the
      framework of a recently developed coupled-mode analysis leading to a set of
      equations governing the amplitudes of pump and second-harmonic frequency fields.
      We predict analytically that second-harmonic generation in prism or grating
      couplers may lead to optical bistability. We believe this to be the first
      demonstration of such an effect in chi((2)) optical resonators.

PMID- 19859351
TI  - Flow and controlled rotation of the spontaneous optical hexagon in KNbO(3).
AB  - The flow and rotation of the optical hexagonal pattern spontaneously formed in a
      photorefractive KNbO(3) crystal is studied. It is demonstrated that the direction
      and speed of rotation can be controlled with an additional erase laser beam.

PMID- 19859354
TI  - Cancellation of four-wave mixing by use of phase shift in a dispersive fiber
      inserted into a zero-dispersion transmission line.
AB  - A simple, effective technique to cancel waves generated by four-wave mixing is
      proposed and experimentally confirmed. A single-mode fiber, which has large
      dispersion at 1.55 microm, is simply inserted into the middle of a dispersion
      shifted fiber transmission line. Dispersion in the single-mode fiber is
      effectively utilized to cause pi phase shift in the light waves generated by four
      wave mixing in the first and second halves of the transmission line so that the
      four-wave mixing is totally canceled.

PMID- 19859355
TI  - Cancellation of third-order nonlinear effects in amplified fiber links by
      dispersion compensation, phase conjugation, and alternating dispersion.
AB  - We show that in principle it is possible to cancel third-order nonlinear effects
      in optical fiber links. The necessary conditions exist in two-segment links, with
      dispersion compensation, phase conjugation, and amplification between the two, as
      well as opposite chromatic dispersion coefficients in the segments. The
      cancellation is independent of loss, modulation format, and modulation frequency.

PMID- 19859356
TI  - Polarization modulation instability in weakly birefringent fibers.
AB  - Modulation instability generated by the coherent interaction of two polarization
      modes in a weakly birefringent optical fiber has been observed in the normal
      dispersion regime. In contrast to previous observations of crossphase-modulation
      instability in the visible, the two generated sidebands have the same
      polarization, which is orthogonal to that of the pump, and their frequency shift
      is readily controlled by variation of the birefringence of the fiber. The
      frequency of the modulation and its qualitative features agree with those
      theoretically predicted.

PMID- 19859358
TI  - Diode-pumped long-pulse-length Ho:Tm:YLiF(4) laser at 10 Hz.
AB  - An optical efficiency of 0.052 under normal mode operation for diode-pumped
      Ho:Tm:YLiF(4) at a pulse repetition frequency of 10 Hz has been achieved. Laser
      output energy of 30 mJ in single Q-switched pulses with 600-ns pulse length were
      obtained for an input energy of 3 J. A diffusion-bonded birefringent laser rod
      consisting of Ho:Tm-doped and undoped pieces of YLF was utilized for 10-Hz
      operation.

PMID- 19859362
TI  - Forced turn-off of a passively Q-switched Nd:YAG pulse by restoration of
      saturable loss by the use of an auxiliary cavity.
AB  - A forced-turn-off mechanism of a passively Q-switched pulse is proposed and
      demonstrated. To investigate the mechanism, we used rate equations and performed
      computer simulations. An auxiliary cavity for a passive Q-switch is inserted into
      a conventional passively Q-switched Nd:YAG laser. Lasing of the auxiliary cavity
      restores the saturable loss and turns off the Q-switched pulse. The measured
      pulse profiles verified the turnoff, and the pulse duration could be controlled
      from 47.0 to 22.0 ns when we varied the auxiliary cavity length. Close agreement
      was obtained between the simulation and experimental results.

PMID- 19859365
TI  - Influence of chromatic dispersion variation along the path of soliton jitter
      control with sliding filters.
AB  - We use perturbation theory to calculate the Gordon-Haus timing jitter in soliton
      communication systems with sliding filters. We analyze the effects of soliton
      parameter changes with distance that are due to the chromatic dispersion
      variation resulting from frequency sliding. We show that the timing-jitter
      control efficiency is nearly independent of the frequency-sliding sign, provided
      the frequency range is the same for both signs.

PMID- 19859357
TI  - Birefringence dispersion measurement in optical fibers by wavelength scanning.
AB  - We describe a method for measuring modal birefringence in optical fibers. It
      combines an interferometric technique with wavelength scanning and permits a
      precise nondestructive measurement of the birefringence along different sections
      of a long optical fiber. The experimental results for high-birefringence fibers,
      10 and 100 m long, are presented. An accuracy of approximately 0.1% is achieved
      in the spectral range of 600-850 nm.

PMID- 19859364
TI  - Experimental analysis and theoretical modeling of a diode-pumped Er:Yb:glass
      microchip laser.
AB  - A comprehensive study of a diode-pumped Er:Yb:glass microchip laser, operating at
      1530-nm wavelength, is presented. The operating conditions wherein a linearly
      polarized, single longitudinal and transverse mode operation is achieved are
      indicated. An optimum pump spot size that minimizes the threshold pump power and
      maximizes the slope efficiency is experimentally found and theoretically
      justified by a space-dependent rate-equation model.

PMID- 19859359
TI  - Stable single-frequency traveling-wave fiber loop laser with integral saturable
      absorber-based tracking narrow-band filter.
AB  - We demonstrate stable single-frequency and polarization operation of a traveling
      wave, Er(3+)-doped fiber loop laser by incorporating an unpumped Er(+3)-doped
      fiber section butted against a narrow-band feedback reflector. The saturable
      absorber acts as a narrow bandpass filter that automatically tracks the lasing
      wavelength, thus ensuring single-frequency operation. Output powers up to 6.2 mW
      at 1535 nm were obtained for launched pump powers of 175 mW at 1064 nm. At this
      output, the relative intensity noise was less than -112 dBy/Hz at frequencies
      above 200 kHz and a laser linewidth of less than 0.95 kHz, whereas the lasing
      frequency was observed to drift slowly (~170 MHz/h) because of environmental
      effects.

PMID- 19859360
TI  - Wavelength shifts of dye lasing in microdroplets: effect of absorption change.
AB  - With addition of an absorber to dye-doped microdroplets, an absorption-dependent
      blue shift in the lasing spectra has been observed. The better the spectral
      overlap between the absorption and the fluorescence spectra of the dye, the
      larger the blue shift. The experimental observations are explained by a simple
      model of dye lasing in an optical cavity that includes losses because of the
      absorber and radiation leakage.

PMID- 19859361
TI  - Influence of the position of the gain medium on the excess noise factor.
AB  - An exact analysis of the excess noise in a two-mirror laser that takes into
      account the intracavity elements and the position of the active medium is
      presented. The influence of the active medium's position and length of the laser
      cavity on the excess noise factor is shown.

PMID- 19859363
TI  - Emission buildup in Q-switched fiber lasers.
AB  - Amplified spontaneous emission is experimentally found to play an important role
      in the dynamics of pulse formation in Q-switched fiber lasers and leads to
      stepwise (or quantized) behavior of the emission buildup. This effect could be
      included in detailed modeling of pulsed fiber lasers and might be interesting in
      some applications.

PMID- 19859367
TI  - Collimation of emissions from a high-power multistripe laser-diode bar with
      multiprism array coupling and focusing to a small spot.
AB  - Twelve beams emitting from twelve stripes, with 200-microm apertures spaced 800
      microm apart, of a 1-cm linear diode array were collimated by a multiprism array
      consisting of fourteen 800-microm-wide prismlets. The spatial intensity
      distribution of each beam was twisted around its optical axis through three total
      reflections in a prismlet, transforming a series arrangement of emitters into a
      parallel arrangement to prevent overlap of adjacent beams. Collimated beams were
      focused to a spot of ~200 microm (FWHM).

PMID- 19859366
TI  - Suppression of multiple pulse formation in actively mode-locked laser diodes by
      gain quenching.
AB  - We propose a new method for obtaining high-power short optical pulses without
      trailing pulses from an actively mode-locked laser diode. To quench the residual
      optical gain, a part of the output is reflected back into the laser diode with
      the orthogonal polarization and the appropriate time delay. A numerical analysis
      using travelingwave rate equations shows that trailing pulses caused by both the
      excess gain and the residual reflection at the laser diode facet are drastically
      suppressed.

PMID- 19859368
TI  - Coherent transport of excitons in quantum-dot chains: role of retardation.
AB  - A model for the coherent transport of excitons along linear, one-dimensional
      arrays of quantum dots accounting for spontaneous emission is presented. The
      interdot coupling is made by means of the coherent emission and reabsorption of
      photons. The long-range nature of the coupling leads to nontrivial dynamics in
      the polarization and in the exciton population with qualitatively different
      behaviors for chains with periods just less than or just greater than integer
      multiples of half the wavelength of the optical transition. Biexponential
      radiative decay of an initially well-localized population is predicted.

PMID- 19859371
TI  - Spatial routing of optical beams through time-domain spatial-spectral filtering.
AB  - We propose a novel new method of temporal-waveform-controlled high-speed passive
      spatial routing of optical beams. The method provides for the redirection of
      optical signals contained within a single input beam into output directions that
      are specified entirely by temporal information encoded on the waveform of each
      incident signal. The routing is effected by means of deflection from spectrally
      structured spatial gratings that may be optically programmed into materials with
      or without intrinsic frequency selectivity.

PMID- 19859369
TI  - Direct measurement of the spectral phase of femtosecond pulses.
AB  - We measure the spectral phase of femtosecond optical pulses using a time
      frequency analog of Young's doubleslit interference. A pair of narrow slits in an
      opaque sheet selects two spectral frequencies from the femtosecond pulse spectrum
      in a zero-dispersion pulse stretcher. Measurement of the temporal phase of a
      family of beat frequencies obtained over a range of slit spacings yields the
      desired spectral phase directly. We demonstrate this technique by accurately
      measuring the quadratic phase added to 80-fs optical pulses by a 6.5-cm block of
      BK-7 glass.

PMID- 19859376
TI  - Raman-noise limit on squeezing in continuous-wave four-wave mixing.
AB  - The continuous-time quantum theory of self-phase modulation (SPM) in lossless,
      dispersionless, single-mode fiber requires a nonzero response time, to capture
      the classical SPM limit properly, and an accompanying Raman noise, to ensure
      commutator preservation. The continuous-wave, four-wave mixing limit of this
      theory is shown to harbor a Raman-noise limit on fiber-based squeezed-state
      generation.

PMID- 19859373
TI  - Widely tunable two-color mode-locked Ti:sapphire laser with pulse jitter of less
      than 2 fs.
AB  - An improved laser setup for reliable dual-wavelength cross mode locking is
      reported. We obtain two perfectly synchronized pulse trains that are
      independently tunable over a wavelength interval as wide as 100 nm and with pulse
      durations below 30 fs. The pulses are shown to be cross correlated with
      interferometric accuracy, thus demonstrating an astonishing potential of the
      nonlinear coupling mechanism.

PMID- 19859372
TI  - True scattering coefficients of turbid matter measured by early-time gating.
AB  - The true scattering coefficients of turbid matter have been determined by use of
      picosecond time-resolved imaging. The scattering coefficients measured by the
      conventional cw collimation method were found to be smaller than those obtained
      from the early-time-sliced ballistic photons.

PMID- 19859374
TI  - Chirped-mirror dispersion-compensated femtosecond optical parametric oscillator.
AB  - We describe the operating characteristics of a femtosecond optical parametric
      oscillator employing chirped mirrors for intracavity group-velocity dispersion
      compensation. Pumped by 760 mW of power from a self-mode-locked Ti:sapphire
      laser, this device provides 100-fs near-transform-limited pulses continuously
      tunable from 1.18 to 1.32 microm with an average power of 100-180 mW. The
      limitations of the present setup and strategies for further pulse shortening are
      discussed.

PMID- 19859370
TI  - Acoustic effect in passively mode-locked fiber ring lasers.
AB  - We present a theory of acoustically induced pulse interaction in a ring fiber
      laser cavity. In most cases the acoustic interaction leads to pulse bunching, but
      in some cases it leads to regular pulse spacing. Our results compare well with
      the experimental data.

PMID- 19859375
TI  - Photorefractive optical fuzzy-logic processor based on grating degeneracy.
AB  - A novel optical fuzzy-logic processor using light-induced gratings in
      photorefractive crystals is proposed and demonstrated. By exploiting grating
      degeneracy, one can easily implement parallel fuzzy-logic functions in
      disjunctive normal form.

PMID- 19859377
TI  - Heterodyne detection of swept-carrier frequency-selective optical memory signals.
AB  - Swept-carrier time-domain optical memories [Opt. Lett. 17, 535 (1992)] are unique
      in that memory output signals occur cotemporally with the excitation field (read
      field) responsible for their generation. We demonstrate that this fact provides
      for the convenient detection of memory signals through their heterodyne
      interference with the cotemporal read field. Memory implementation is
      dramatically simplified.

PMID- 19859378
TI  - Least-squares fitting of the phase map obtained in phase-shifting electronic
      speckle pattern interferometry.
AB  - A new method has been developed to remove noise from the deformation phase map
      obtained by a phase-shifting electronic speckle pattern interferometry. Unlike
      usual methods, it estimates almost noise-free phase values directly from the
      distributions of the intensity differences of four interference patterns by a
      least-squares fit. The fluctuations of uniform deformation phases are reduced to
      less than 0.05 rad with a 5 x 5 pixel fitting window. The so-called sawtooth
      phase jumps that are due to the use of arctangent functions are retained sharply
      in this method.

PMID- 19859379
TI  - Multispecies Raman imaging in flames by use of an unintensified charge-coupled
      device.
AB  - The application of an unintensified charge-coupled device (CCD) to one
      dimensional multispecies Raman flame imaging is demonstrated. Relative signal
      strength is improved by the higher quantum efficiency of the unintensified CCD
      versus an intensified CCD generally used for Raman imaging. Experimental
      comparisons of unintensified and intensified CCD systems show ~40% improvement in
      the signal-to-noise ratios of major-species Raman signals for laboratory-scale
      H(2)-air flames. The maximum possible signal improvement is limited by the 40%
      transmission efficiency of the ferroelectric liquid-crystal light valve used to
      gate the CCD, although the light valve is demonstrated to be unnecessary for low
      luminosity flames.

PMID- 19859382
TI  - Dynamic self-pumped phase-conjugating mirror based on the bacteriorhodopsin
      variant D96N: comment.

PMID- 19859380
TI  - Double-phase-conjugate mirror in CdTe:V with elimination of conical diffraction
      at 1.54 microm.
AB  - We have fabricated a double-phase-conjugate mirror (DPCM) in a single crystal of
      vanadium-doped cadmium telluride. Because of the high gain in the near-infrared
      region, a DPCM is possible at a telecommunication wavelength of 1.54 microm in
      this material. Experimental and theoretical thresholds for the DPCM are compared,
      and an experimental diffraction efficiency of 7.4% is reported. Conical
      diffraction has been eliminated by the method of cylindrical lenses. We propose
      to use this astigmatic configuration to enhance the capacity of interconnections
      between fibers with a single crystal in a vector-matrix architecture.

PMID- 19859385
TI  - Self-mode-locked diode-pumped Cr:LiSAF laser: erratum.

PMID- 19859381
TI  - High-efficiency multilayer dielectric diffraction gratings.
AB  - The design and performance of a new type of high-efficiency diffraction grating
      for use in either transmission or reflection are described. The gratings are
      produced in a multilayer dielectric coating deposited upon optically flat
      substrates. By proper design of the multilayer stack and grating structure, a
      diffraction efficiency in excess of 96% for polarized light in the m = -1 order
      in reflection has been achieved.

PMID- 19859387
TI  - Photoreversible birefringence in doped Vycor glass.

PMID- 19859383
TI  - Dispersive interferometric profilometer: erratum.

PMID- 19859391
TI  - Planar optical lattice of TiO<inf>2</inf> particles.

PMID- 19859384
TI  - Mode properties of a plasma waveguide for intense laser pulses: erratum.

PMID- 19859388
TI  - Sparse matrix wave-front estimators for adaptive-optics systems for large ground
      based telescopes.

PMID- 19859386
TI  - Direct solution to the inverse scattering problem for surfaces from near-field
      intensities without phase retrieval.

PMID- 19859390
TI  - Emission linewidth of laser action in random gain media.

PMID- 19859389
TI  - Optical fabrication of microlenses in chalcogenide glasses.

PMID- 19859392
TI  - Visibility of individual particles inside a dense particle ensemble.

PMID- 19859394
TI  - Investigation of tetrabenzporphyrin by the Z-scan technique.

PMID- 19859393
TI  - Scanning near-field optical probe with ultrasmall spot size.

PMID- 19859395
TI  - Reduction of the soliton interaction and the Gordon-Haus effect by optical phase
      conjugation.

PMID- 19859398
TI  - Plate-formed mutually pumped phase conjugator.

PMID- 19859396
TI  - Observation of multireflections from cat self-pumped phase conjugators with Cu
      doped
      (K<inf>0.5</inf>Na<inf>0.5</inf>)<inf>0.2</inf>(Sr<inf>0.75</inf>Ba<inf>0.25</inf
      )<inf>0.9</inf>Nb<inf>2</inf>O<inf>6</inf> crystals and conjugation fidelity
      analysis.

PMID- 19859400
TI  - Polarization dependence of ultrafast nonlinear refraction in an AlGaAs waveguide
      at the half-band gap.

PMID- 19859397
TI  - Efficient low-intensity optical phase conjugation based on coherent population
      trapping in sodium.

PMID- 19859401
TI  - Hidden mechanism for mode locking solid-state lasers by use of a slow off
      resonant saturable absorber.

PMID- 19859399
TI  - Measurement of the nonlinear refractive index in optical fiber by the cross-phase
      modulation method with depolarized pump light.

PMID- 19859406
TI  - Polarization-independent electro-optic depolarizer.

PMID- 19859402
TI  - Intermodal dispersion in two-core optical fibers.

PMID- 19859404
TI  - 10-GHz optical soliton transmission experiment in a sliding-frequency
      recirculating fiber loop.

PMID- 19859403
TI  - Pressure sensitivity of rocking filters fabricated in an elliptical-core optical
      fiber.

PMID- 19859408
TI  - Room-temperature upconversion fiber laser tunable in the red, orange, green, and
      blue spectral regions.

PMID- 19859409
TI  - Generation of 1.5-mu m radiation through intracavity solid-state Raman shifting
      in Ba(NO<inf>3</inf>)<inf>2</inf> nonlinear crystals.

PMID- 19859407
TI  - Compact XeF (C -> A) and iodine laser optically pumped by a surface discharge.

PMID- 19859410
TI  - Single-frequency Q-switched ring laser with an antiresonant Fabry-Perot saturable
      absorber.

PMID- 19859405
TI  - Analytical expressions for effective indices in a three-waveguide coupler.

PMID- 19859411
TI  - Effect of random multiple light scattering on the laser action in a binary-dye
      mixture.

PMID- 19859412
TI  - Observation of lasing on the two J = 0-1, 3p-3s transitions at 26.1 and 30.4 nm
      in neonlike vanadium.

PMID- 19859413
TI  - Continuous frequency tuning of a cw optical parametric oscillator through tuning
      of its pump source.

PMID- 19859415
TI  - Optical spectrum analyzer of a new design.

PMID- 19859414
TI  - Inducing periodic oscillations from chaotic oscillations of a compound-cavity
      laser diode with sinusoidally modulated drive.

PMID- 19859416
TI  - Measurement of femtosecond pulses in the focal point of a high-numerical-aperture
      lens by two-photon absorption.

PMID- 19859417
TI  - Kerr-lens mode-locked visible transitions of a Pr:YLF laser.

PMID- 19859418
TI  - Chirped-pulse amplification of ultrashort pulses with a multimode Tm:ZBLAN fiber
      upconversion amplifier.

PMID- 19859419
TI  - Generation of high-fidelity programmable ultrafast optical waveforms.

PMID- 19859420
TI  - A priori and adaptive Wiener filtering with joint transform correlators.

PMID- 19859421
TI  - General optical implementations of fractional Fourier transforms.

PMID- 19859422
TI  - Time-gated imaging with an ultrashort-pulse, laser-produced-plasma x-ray source.

PMID- 19859423
TI  - Phase-conjugate quantum communication with optical heterodyne detection.

PMID- 19859424
TI  - Long-distance frequency-division interferometer for communication and quantum
      cryptography.

PMID- 19859425
TI  - Spectrally controlled interference of picosecond time-and-space-domain holograms.

PMID- 19859426
TI  - Cavity ring-down technique and its application to the measurement of ultraslow
      velocities.

PMID- 19859427
TI  - Two-wavelength interferometer based on a two-color laser-diode array and the
      second-order correlation technique.

PMID- 19859428
TI  - Maximum-entropy optical spectrum analyzer.

PMID- 19859429
TI  - High-optical-density out-of-band spectral transmittance measurements of bandpass
      filters.

PMID- 19859430
TI  - Spatial optical solitons governed by quadratic nonlinearity: erratum.

PMID- 19859431
TI  - Backscatter signatures of knots: errata.

PMID- 19859432
TI  - Determination of phase mode components in terms of local wave-front slopes: an
      analytical approach.
AB  - An analytical formulation that relates the modal expansion coefficients of a
      given wave front to its local transverse phase derivatives is proposed. The modal
      coefficients are calculated as a weighted integral over the wave-front slopes.
      The weighting functions for each mode are the components of a two-dimensional
      vector whose divergence equals the corresponding mode function. This approach is
      useful for analytical phase reconstruction from the input data provided by
      shearing interferometers or Hartmann-Shack wave-front sensors. Numerical results
      for a simulated experiment in terms of a set of Zernike polynomials are given.

PMID- 19859433
TI  - Channeling of terawatt laser pulses by use of hollow waveguides.
AB  - Subpicosecond laser pulses at power levels in excess of 1 TW were channeled
      through hollow microcapillary tubes by use of a combination of grazing-incidence
      dielectric and plasma-wall reflection mechanisms. Maximum input and output
      intensities were 10(17) and 10(16) W/cm(2) through 50-microm radius by 3-cm-long
      glass microcapillary tubes with as few as two waveguide modes being excited. 133
      microm radius tubes as long as 13 cm resulted in successful channeling with an
      extinction coefficient of 0.2 cm(-1) and a plasma-wall reflectivity of 80%.

PMID- 19859434
TI  - Different temporal behavior for the forward- and backward-circulating radiation
      within a microdroplet.
AB  - Spatially resolved nonlinear scattering of a train of picosecond pulses from
      ethanol microdroplets is investigated. Different time behavior is observed for
      light with the same and the opposite sense of circulation as the input-coupled
      light. The forward-circulating light exhibits a smooth, delayed pulse-to-pulse
      growth, attributed to increased input coupling with time induced by the laser
      pulses. The backward-circulating light has an irregular time behavior, attributed
      to near-backward stimulated Brillouin scattering. Increased scattering as a
      result of CO(2) (compared with He) dissolved gas is demonstrated by an intensity
      decrease of the spatially precessed radiation on a cavity resonance.

PMID- 19859435
TI  - Time-domain soliton filter based on a semidissipative dual-core fiber.
AB  - We propose a time-domain dual-core fiber filter that greatly reduces soliton
      jitters and noise power in its application to ultrahigh-speed soliton
      communication systems. This filter is simply a dual-core fiber that has one core
      with negligible loss and the other with large loss.

PMID- 19859436
TI  - How accurate is optical second-harmonic generation?
AB  - We have checked whether the frequency ratio between fundamental and second
      harmonic optical frequencies is exactly 1:2 by measuring the frequency difference
      between the second harmonics of two diode lasers and comparing it with the
      frequency difference of the fundamentals. We have improved the 30-year-old
      experimental limit on the accuracy of the 1:2 frequency ratio by 7 orders of
      magnitude for frequency-dependent shifts to 2.3 parts in 10(13) for a KNbO(3)
      crystal.

PMID- 19859437
TI  - Self-pumped phase conjugation of diffusely reflected light in a KNSBN crystal.
AB  - We report self-pumped phase conjugation in a Cu:KNSBN crystal for light diffusely
      reflected from a rough surface. We have demonstrated wave-front distortion
      compensation for diffuse reflection. We have experimentally studied the
      dependence of the phase-conjugation reflectivity on the f-number of a lens
      imaging the spot upon the diffuser into the crystal and on the size of the beam
      incident upon the diffuser surface. Finally, with a Michelson interferometer we
      observed the phase fluctuation of the phase-compensated wave front.

PMID- 19859438
TI  - Grating-assisted phase-matched second-harmonic generation from a polymer
      waveguide.
AB  - Diffraction gratings can be used to achieve phase matching between the
      fundamental modes of a slab or confined waveguide. Compared with the usual
      techniques such as quasi-, Cerenkov, and intermodal phase matching, the matching
      method used here involves spatial harmonics of the guided electromagnetic field
      that are generated by the corrugated grating. This grating acts simultaneously as
      a linear waveguide coupler at both the pump and harmonic frequencies. Using the
      third spatial harmonic, we report what we believe to be the first observation of
      grating-assisted phase-matched second-harmonic generation between
      counterpropagating TM(0) modes of an organic waveguide.

PMID- 19859439
TI  - Efficient generation of infrared picosecond pulses from 10 to 20 microm.
AB  - Starting with 11-ps pulses of 8-mJ energy at 1.064 microm and using a sequence of
      a KTP crystal and a CdSe crystal, we generate infrared pulses from 10 to 20
      microm with energies ranging from 40 to 5 microJ. The quantum efficiency of the
      last stage is higher than 50% from 10 to 18 microm.

PMID- 19859440
TI  - Efficient conversion of high-power narrow-band Ti:sapphire laser radiation to the
      mid-infrared in KTiOAsO(4).
AB  - Photon conversion efficiencies of 60% at 2.92 microm and 25% at 4.5 microm of a
      high-power injection-seeded Ti:sapphire laser have been achieved by difference
      frequency mixing with the new crystal KTiOAsO(4).

PMID- 19859441
TI  - Measurements of the tensor properties of third-order nonlinearities in wide-gap
      semiconductors.
AB  - We extend the z-scan technique to provide for measurements of the sign and the
      magnitude of all the independent components of chi((3)) for isotropic and cubic
      symmetry materials. This technique is used to measure the dispersion of the
      tensor components of the real and the imaginary parts of chi((3)) for various
      wide-gap semiconductor materials by use of femtosecond laser pulses. Our
      measurements of the polarization dichroism of the nonlinear-index and two-photon
      absorption coefficients are in fair agreement with recent theoretical
      calculations; however, substantial discrepancies exist between the measured and
      predicted values for the corresponding anisotropy parameters.

PMID- 19859442
TI  - Transmission control of dark solitons by means of nonlinear gain.
AB  - Transmission control of dark solitons against various perturbations is possible
      by use of amplifiers with nonlinear gain. Stable propagation of gray and/or black
      solitons is achieved even in the presence of the Raman effect and mutual
      interactions between neighboring dark solitons.

PMID- 19859443
TI  - Light-induced director reorientation through the electroclinic effect and optic
      axis rotation in a chiral smectic A liquid crystal.
AB  - We report the observation of light-induced director reorientation under the
      application of an electric field in a chiral smectic A liquid crystal owing to
      the temperature dependence of the electroclinic coefficient. We also demonstrate
      the occurrence of another light-induced phenomenon that leads to optic axis
      rotation, whose origin is not yet clear. Finally, we show that thermal indexing
      cannot be neglected when fitting the experimental data.

PMID- 19859444
TI  - Kerr-effect-induced S-R flip-flop operation in an optical fiber loop resonator
      with double couplers.
AB  - We carry out a theoretical analysis of Kerr bistability in a double-coupler
      optical fiber loop resonator in a case of two coexisting input optical fields,
      and we propose a set-reset (S-R) flip-flop operation that uses two input ports.
      We found that in the optimum case set and reset operation can be achieved at
      relatively low optical input powers.

PMID- 19859445
TI  - Linearly and nonlinearly chirped Bragg gratings fabricated on curved fibers.
AB  - We can introduce chirping, or a variation in the periodicity of a Bragg grating,
      into an optical fiber by writing gratings on curved optical fibers. By precisely
      specifying the curvature, we can obtain linear, quadratic, and square-root
      chirped gratings. Experimental and numerical verifications of the relationships
      between curvature and grating characteristics are presented.

PMID- 19859446
TI  - Photorefractive spatial mode converter for multimode-to-single-mode fiber-optic
      coupling.
AB  - We report what is to our knowledge the first experimental demonstration of a
      photorefractive spatial mode converter (based on mutually pumped phase
      conjugation) that couples light efficiently from a multimode fiber into a
      singlemode fiber with an extremely large degree of tolerance to misalignment.
      Using an argon laser (514.5 nm) and a barium titanate crystal, we have
      demonstrated that the laser light can be coupled from a multimode fiber (core
      diameter 100 microm, numerical aperture 0.37) into a single-mode fiber (core
      diameter 2.9 microm, numerical aperture 0.11), with an efficiency of ~15% and an
      alignment tolerance of ~100 microm. The coupling efficiency is more than 2 orders
      of magnitude, and the tolerance to misalignments is more than 30 times better
      than the corresponding values achievable by conventional techniques.

PMID- 19859447
TI  - Effect of modulation instability on phase modulation-amplitude modulation
      conversion in optical fibers.
AB  - Phase modulation-amplitude modulation conversion in dispersive fibers is affected
      by nonlinear phase modulation and modulation instability. A differential equation
      is derived under adiabatic approximations and is solved analytically. The results
      agree well with experimental values. A simple measurement of the nonlinear coeff
      icient is thus feasible.

PMID- 19859448
TI  - Algebraically decaying modes of dielectric planar waveguides.
AB  - We show analytically that, at a critical point where the effective refractive
      index of a mode coincides with the bulk index of a substrate region, for certain
      graded-index planar waveguides there exists a family of bound modes with
      algebraic (power-law) tails in the evanescent field.

PMID- 19859449
TI  - Failure of the leaky-mode representation near the waveguide mode cutoff.
AB  - Improper eigenmodes of the planar waveguide dispersion relation, or leaky modes,
      are often used to represent the nonbound optical field in planar waveguides. Here
      we show that the improper leaky solutions give an inadequate description of the
      nonbound field for the important case of a waveguide just below cutoff.

PMID- 19859450
TI  - Planar Fresnel lens photoimprinted in a germanium-doped silica optical waveguide.
AB  - A gradient-thickness Fresnel lens was photoimprinted in the germanium-doped core
      layer of a single-mode planar waveguide on silica by exposure to ultraviolet
      light through a mask, which increases the refractive index in the lens region by
      approximately 5 x 10(-3). The lens is used to collimate the output of a standard
      single-mode optical fiber butt coupled to the waveguide at a wavelength of 1.3
      microm. The method is applicable to the mass production of complex diffractive
      elements in a planar waveguide geometry.

PMID- 19859451
TI  - Photorefractive recording by a special mechanism in planar LiNbO(3) waveguides.
AB  - Recording of holographic gratings in z-cut LiNbO(3) waveguides with
      extraordinarily (TM) polarized light is demonstrated. In this geometry,
      photovoltaic currents perpendicular to the guiding layer and the grating vector
      set up space-charge fields. The mechanism has no equivalent in bulk material.

PMID- 19859452
TI  - Amplification of femtosecond pulses to 1 J in Cr:LiSrAlF(6).
AB  - We have developed a large-aperture, flash-lamp-pumped Cr:LiSrAlF(6) (Cr:LiSAF)
      amplifier for use in a femtosecond chirped-pulse amplifier system. Optimum design
      of the 19-mm-diameter amplifier results in a single-pass gain of 5 with good beam
      quality. This amplifier produces 1.05-J pulses after compression, with a width of
      125 fs at a repetition rate of 0.05 Hz.

PMID- 19859453
TI  - Deep-UV generation by frequency quadrupling of a high-power GaAlAs semiconductor
      laser.
AB  - Tunable UV radiation near 215 nm was produced by frequency quadrupling the 860-nm
      emission of a mode-locked external-cavity compound semiconductor laser containing
      a tapered GaAlAs amplifier. A KNbO(3) crystal generated the 430-nm second
      harmonic, which was doubled by a beta-BaB(2)O(4) crystal, producing tunable UV
      radiation with as much as 15 microW of average power.

PMID- 19859454
TI  - 300-W cw diode-laser side-pumped Nd:YAG rod laser.
AB  - We report on the laser performance and power scaling properties of diode-laser
      side-pumped Nd:YAG rod lasers operating at high cw output powers. Applying a pump
      power of 1100 W cw in a ninefold pump geometry, we obtain an output power of more
      than 300 W in multimode operation. For a comparable pump scheme an output power
      of more than 45 W in TEM(00) mode operation is realized with an optical-to
      optical efficiency of more than 11%.

PMID- 19859455
TI  - Thermal effects on the threshold of vertical-cavity surfaceemitting lasers: first
      and second-order phase transitions.
AB  - We investigate the threshold behavior of vertical-cavity surface-emitting lasers
      (VCSEL's) by solving the set of coupled equations for carrier density, field
      amplitude, and plasma and lattice temperatures. We show that, because of plasma
      heating and lattice heating, the threshold of VCSEL's can be continuous or
      discontinuous with bistability between lasing and nonlasing states
      (correspondingly second- or f irst-order phase transition), depending on the
      relative position of the cavity frequency to the gain bandwidth and on the
      ambient (substrate) temperature of the device.

PMID- 19859456
TI  - Broadband multilayer antireflection coating for semiconductor laser facets.
AB  - Using a triple-layer antireflection coating of Al(2)O(3), Si, and SiO(2), we have
      achieved a minimum facet reflectivity of 1 x 10(-6) and a bandwidth of 90 nm for
      a reflectivity of 5 x 10(-5) or less for 1550-nm center-wavelength InGaAsP
      semiconductor lasers. A facet reflectivity of 3 x 10(-6) and a bandwidth of 30 nm
      for a reflectivity of 5 x 10(-5) were achieved for 1310-nm InGaAsP lasers. This
      coating is applicable to broadband external-cavity-tuned laser sources, edge
      emitting light-emitting diodes, and semiconductor laser amplifiers.

PMID- 19859457
TI  - Self-mode-locked diode-pumped Cr:LiSAF laser producing 34-fs pulses at 42-mW
      average power.
AB  - We describe a self-mode-locked diode-pumped Cr:LiSAF laser producing almost
      bandwidth-limited tunable pulses of 34-fs duration at an average power of 42 mW.
      We discuss the capacity of this laser to produce even-shorter pulses and how
      their quality may be improved by reduction of pulse-duration limiting effects.

PMID- 19859458
TI  - Time-bandwidth product of chirped sech(2) pulses: application to phase-amplitude
      coupling factor measurement.
AB  - An exact analytical expression for the time-bandwidth product DeltatDeltaf of
      chirped sech(2) pulses is derived. The relation can be expressed by DeltatDeltaf
      = 0.1786 arcosh(cosh pialpha + 2) as a function of the laser's phase-amplitude
      coupling factor alpha. An experimental measurement of the alpha factor that
      relies on this formula is discussed.

PMID- 19859459
TI  - Nonlinear temporal diffraction and frequency shifts resulting from pulse shaping
      in chirped-pulse amplification systems.
AB  - We present experimental results of the amplification of strongly amplitude
      modulated chirped pulses resulting from the coherent addition of two delayed
      short pulses. The nonlinearities in the amplifier chain induce a temporal
      diffraction resulting in prepulses and postpulses, in addition to the two main
      pulses when compressed. Simultaneously, temporal-resolved and spectral-resolved
      output pulses show that the prepulses and postpulses are blue shifted and red
      shifted, respectively, explaining the causality of the system.

PMID- 19859460
TI  - Wavelength-division multiplexing with femtosecond pulses.
AB  - We demonstrate wavelength-division multiplexing with a single broadband
      femtosecond source by slicing the 3.7-THz spectral bandwidth of 85-fs laser
      pulses into 16 channels that are modulated individually.

PMID- 19859461
TI  - Diode-pumped mode-locked Nd:glass lasers with an antiresonant Fabry-Perot
      saturable absorber.
AB  - We demonstrate passively mode-locked diode-pumped Nd:glass lasers with different
      media such as silicate, phosphate, and fluorophosphate that are homogeneously or
      inhomogeneously broadened. An antiresonant Fabry-Perot saturable absorber starts
      and stabilizes the soliton mode-locked Nd:glass lasers, producing pulses as short
      as 130 fs at an average output power of 100 mW. With a cw Ti:sapphire pump laser
      we obtain pulses as short as 90 fs.

PMID- 19859462
TI  - Image restoration by a novel method of parallel projection onto constraint sets.
AB  - Image restoration from degraded observations and from properties that the image
      is supposed to satisfy has been approached by the method of projections onto
      convex constraint sets. Previous attempts have incorporated only partially the
      knowledge that we possess about the image to be restored because of difficulties
      in the implementation of some of the projections. In the parallel-projection
      algorithm presented here the a priori knowledge can be fully exploited. Moreover,
      the algorithm operates well even if the constraints are nonconvex and/or if the
      constraints have an empty intersection, without a limitation on the (finite)
      number of constraint sets.

PMID- 19859463
TI  - Stellar speckle imaging by reference to different-colored specklegrams.
AB  - Stellar specklegrams at different wavelengths are examined. The position of the
      brightest speckle at one wavelength is shown to coincide nearly with that at a
      widely separated wavelength. The shift-and-add operation for specklegrams at one
      wavelength produces a high-resolution stellar image at the other wavelength. We
      show that the shift-and-add operation at 450 nm results in a high-resolution
      image at 800 nm by use of observational speckle data from which specklegrams at
      these wavelengths are taken simultaneously.

PMID- 19859464
TI  - Optical interpretation of a complex-order Fourier transform.
AB  - It is demonstrated that the definition of a fractional-order Fourier transform
      can be extended into the complexorder regime. A complex-order Fourier transform
      deals with the imaginary part as well as the real part of the exponential
      function in the integral. As a result, while the optical implementation of
      fractional-order Fourier transform involves gradient-index media or spherical
      lenses, the optical interpretation of complex-order Fourier transform is
      practically based on the convolution operation and Gaussian apertures. The beam
      width of a Gaussian beam subjected to the complex-order Fourier transform is
      obtained analytically with the ABCD matrix approach.

PMID- 19859465
TI  - Optical phase retrieval by phase-space tomography and fractional-order Fourier
      transforms.
AB  - Phase-space tomography is experimentally demonstrated for the determination of
      the spatially varying amplitude and phase of a quasi-monochromatic optical field
      by measurements of intensity only. Both fully and partially coherent sources are
      characterized. The method, which makes use of the fractional-order Fourier
      transform, also yields the Wigner distribution of the field and works in one or
      two dimensions.

PMID- 19859466
TI  - Ultraviolet-radiation-induced chemical reactions through one and two-photon
      absorption processes in GeO(2)-SiO(2) glasses.
AB  - Photochemical reactions in 10 GeO(2)-90 SiO(2) glass induced by irradiation with
      excimer lasers (KrF, 5.0 eV, XeCl, 4.0 eV) and a Hg lamp (4.9 eV) were examined.
      The irradiation with excimer lasers generated two types of paramagnetic defect,
      an electron-trapped center associated with fourfold coordinated Ge ions and a
      self-trapped hole center on bridging oxygen. Taking the optical band gap (~7.1
      eV) of the glass obtained in this work and the power density of laser pulses [10
      90 mJ/(cm(2) pulse), pulse duration 20 ns] into account, we concluded that these
      centers were formed by band-to-band excitation by two-photon absorption process.
      On the other hand, the lamp illumination ( 16 mW/cm(2)) caused the formation of
      Ge E' centers from preexisting oxygen-vacancy-type defects by the one-photon
      absorption process. These two kinds of reaction proceed independently, depending
      on the power densities of UV beams, at least in our experimental condition.

PMID- 19859467
TI  - Short-coherence-length multipass interferometer.
AB  - A simple multipass interferometer is described that takes advantage of the
      limited coherence length of a light source in order to increase the sensitivity.
      The sensitivity augmentation is accomplished by insertion of a beam splitter into
      one leg of the interferometer, thereby achieving multiple reflections between the
      end mirror and the beam splitter. The path length of the other leg is then varied
      corresponding to one, two, three, or more reflections, resulting in a onefold,
      twofold, threefold, etc. increase in sensitivity.

PMID- 19859468
TI  - Collisional Raman linewidths of nitrogen at high temperature (1700-2400 K).
AB  - New high-temperature measurements of collisional linewidths of the Raman Q branch
      of nitrogen have been performed at 1700-2400 K with stimulated Raman spectroscopy
      in a tungsten filament. We fitted these data together with previous data obtained
      in the 295-1500-K range to redetermine the parameters of the relaxation models
      used in coherent anti-Stokes Raman spectroscopy thermometry. The improvement in
      the accuracy of the temperature measurement has been checked. Semiclassical
      calculations of linewidths in the 1700-2400-K range agree with the experimental
      data and have been extended to even higher temperatures.

PMID- 19859469
TI  - Lifetime of the metastable 6s' [(1/2)](0) clock state in xenon.
AB  - To investigate the potential of a proposed optical frequency standard, we have
      measured the lifetime of the metastable 6s' [(1/2)](0) state in xenon. Magneto
      optically trapped xenon atoms were prepared in the 6s' [(1/2)](0) state, and the
      time dependence of the vacuum-ultraviolet decay signature was analyzed. The total
      decay rate of 75(3) s(-1) is the sum of a 7.8(38)-s(-1) spontaneous emission rate
      (1-sigma uncertainties) and a much larger deexcitation rate that is due to a
      transition driven by room-temperature blackbody radiation.

PMID- 19859470
TI  - Raman spectroscopic studies of diamond in Intralipid.
AB  - Raman spectroscopic measurements were performed to determine the presence of a
      diamond located within an Intralipid scattering medium. The Raman signature of
      the diamond was recorded for varying thicknesses and concentrations of the
      Intralipid by use of a 514-nm argon-ion laser and a cw 785-nm Ti:sapphire laser.
      Results show how Raman spectroscopy can be used as a diagnostic tool for
      identifying objects embedded within scattering media. In particular, future
      applications could include tissue diagnostics performed in vivo.

PMID- 19859472
TI  - Pulsed-image generation and detection.
AB  - We describe an experimental system that programs three-dimensional optical fields
      to 200-fs resolution over a 10-ps window by using photorefractive volume
      reflection holograms in lithium niobate. These pulsed images are detected with an
      imaging interferometric cross correlator.

PMID- 19859471
TI  - Polarization-independent optical switch composed of holographic optical elements.
AB  - A novel 2 x 2 polarization-independent optical switch with holographic optical
      elements is proposed. The switch consists of an electro-optic half-wave plate
      sandwiched between two pairs of holographic polarization beam splitters. Normally
      incident input and output couplings of this compact and lightweight device
      provide better flexibility and easier alignment for system applications.

PMID- 19859473
TI  - Synthetic near-field holograms with localized information.
AB  - Synthetic near-field holograms with large apertures are suitable for three
      dimensional display applications. For the computation of near-field hologram
      structures, algorithms that involve large Fourier transforms are time consuming.
      A simple method is presented that shortens the generation process.

PMID- 19859474
TI  - Spatial frequency multiplexing of optical fiber sensor arrays.
AB  - A new technique to multiplex interferometric optical fiber sensors in the spatial
      frequency domain is reported that is especially suitable for applications in
      smart structures and materials. It can greatly reduce the number of fiber-optical
      devices in the network system and employs a high-speed noniterative phase
      retrieval technique to trace the phase changes in each fiber sensor. In addition,
      the sensor system operation is virtually immune to the polarization fading
      problem without the need for polarization-maintaining fibers or any special
      devices. A preliminary investigation based on computer simulation has been
      undertaken to assess the system's feasibility and performance.

PMID- 19859475
TI  - Inversion of irradiance moments.
AB  - A relationship is derived between the irradiance moments of an object and the
      irradiance moments of the object's image. Accurate knowledge of the system's
      point-spread-function irradiance moments permits inversion of this relationship.
      It is shown that the inversion is well conditioned, and Monte-Carlo simulation
      results of a two-point object that demonstrate superresolution are presented.

PMID- 19859476
TI  - Simple binary optical elements for aberration correction in confocal microscopy.
AB  - When a confocal fluorescence microscope with a high-numerical-aperture oil
      immersion objective is focused deep into an aqueous medium, aberrations result
      that degrade image quality. We have designed and fabricated a simple two-level
      binary phase mask that partially corrects these aberrations, improving axial
      resolution. We present the design and some confirming results.

PMID- 19859477
TI  - Crystallographically limited submicrometer gratings in (100) and (211) silicon.
AB  - We demonstrate the fabrication of submicrometer gratings in (100) and (211) Si
      with periodicities that are appropriate for normal-incidence coupling into Ge-Si
      waveguides. Gratings of periodicities in the 0.25-0.75microm range were
      fabricated by a standard holographic lithography technique. Crystallographically
      preferential wet etching that effectively terminates at the {111} family of
      planes facilitates the fabrication of symmetric gratings in (100) Si and of
      blazed gratings in (211) Si. The gratings used in this study are appropriate for
      the fabrication of integrated first- and second-order, normal-incidence grating
      couplers at a 1.30-microm wavelength. The blazed gratings show a preferential
      coupling of more than 80% of the total diffraction into the (+1) diffraction
      order at normal incidence. The maximum first-order diffraction efficiency
      obtained with these gratings was approximately 28% in (100) Si and 23% in (211)
      Si.

PMID- 19859478
TI  - Simple coherence measurement with a modified Lau interferometer: erratum.

PMID- 19859479
TI  - Evolution of the Stokes parameters in optically anisotropic media.
AB  - The evolution of the Stokes parameters in optically anisotropic media is
      characterized by a set of coupled nonlinear first-order differential equations.
      The incident quasi-monochromatic plane-wave field is assumed to be statistically
      stationary and of arbitrary state of polarization. The optical medium is assumed
      to be linear, passive, and characterized by a differential Mueller matrix. It is
      shown that the set of these equations provides an efficient tool for the analysis
      of the propagation of partially polarized light in anisotropic media. As an
      example, we analyze the evolution of a beam of light propagating in a cholesteric
      liquid crystal. We also investigate how an additive temporal randomness on the
      differential Mueller matrix can modify the evolution of Stokes parameters in this
      medium.

PMID- 19859480
TI  - Pattern generation method by direct toner irradiation.
AB  - A novel method for toner pattern generation is proposed. The image pattern is
      simply formed by direction of a light flash through a pattern mask to expose
      toner on a transparent support. The force of movement from light of which the
      optical energy density was 0.73 J/cm(2) and the exposure time was 0.43 ms FWHM
      was estimated to be more than 2.8 x 10(-9) N. The cause of the transfer was
      examined, and ablation of toner was determined to be the most likely. If this
      method can be applied to a printer, a simple process to form images may be
      realized.

PMID- 19859481
TI  - Mode analysis of optical waveguides: a new approach.
AB  - We propose a new numerical method for extracting extreme eigenvalues and the
      corresponding eigenmodes for very large Hermitian matrices. The method is
      applied, for what we believe is the first time, to the mode analysis of
      arbitrarily shaped optical waveguides. Compared with results obtained by other
      numerical methods, it is shown that our method is powerful with respect to the
      analysis, modeling, and optimum design of lossless optical waveguides.

PMID- 19859482
TI  - Anomalous wavelength dependence of the dye-induced optical reorientation in
      nematic liquid crystals.
AB  - We report on Z-scan measurements of the spectral dependence of dye-induced
      enhancement of optical torque in nematic liquid crystals. It is found that the
      enhancement factor changes sign from positive to negative as photon energy
      increases from 2.4 to 2.7 eV. Modification of our earlier model is proposed to
      describe the observed spectral dependence.

PMID- 19859483
TI  - Angular Goos-Hanchen effect in curved dielectric microstructures.
AB  - A macroscopic angular Goos-Hanchen effect at total reflection on curved
      interfaces is studied experimentally. The results are compared with the complex
      angular-momentum model of quasi-critical scattering. An extremum in angular
      deflection, which has not yet been predicted by any theory other than exact Mie
      scattering computations, is identified at low size parameters.

PMID- 19859484
TI  - Sulfonated polystyrene as a new gradient-index medium for light-focusing
      elements.
AB  - We have discovered that the sulfonation of polystyrene can form a gradient-index
      medium useful for lightfocusing purposes. We found that the refractive index of
      sulfonated polystyrene varies with the degree of sulfonation and that the
      refractive index of the fully sulfonated polystyrene decreased by approximately
      0.06 at 0.633 microm from that of pure polystyrene.

PMID- 19859485
TI  - Optical phase conjugation in a magnetic photorefractive semiconductor CdMnTe.
AB  - Magneto-optical phase conjugation was performed in a diluted magnetic
      photorefractive semiconductor crystal CdMnTe under an applied magnetic field. The
      magnetic field removes time-reversal symmetry and quenches orthogonal components
      of the phase-conjugate signal for selected field strengths. The experimental
      results as functions of magnetic field and incident polarization angle are in
      good agreement with coupled-mode theory with transmission gratings during magneto
      photorefractive mixing.

PMID- 19859486
TI  - Tuning the properties of poly(p-phenylenevinylene) for use in all-optical
      switching.
AB  - We show that, as the conjugation length of poly(p-phenylenevinylene) increases,
      the ratio of its two-photon absorption coeff icient to third-order nonlinearity
      at 800 nm decreases, rendering the material suitable for alloptical switching.

PMID- 19859487
TI  - Time-division multiplexing of polarization-insensitive fiber-optic Michelson
      interferometric sensors.
AB  - A system of time-division multiplexing of polarization-insensitive fiber-optic
      Michelson interferometric sensors that uses Faraday rotator mirror elements is
      demonstrated. This system is constructed with conventional low-birefringence
      single-mode fiber and is able to solve the polarization-fading problem by a
      combination of Faraday rotator mirrors with unbalanced Michelson interferometers.
      The system is lead-fiber insensitive and has potentials for practical field
      applications.

PMID- 19859488
TI  - Narrow-band acousto-optic tunable filtering in a two-mode fiber.
AB  - We demonstrate an optical filter that utilizes acousto-optic coupling between the
      spatial modes that propagate in a two-mode elliptical-core fiber. The optical
      bandwidth at 1090 nm is 0.85 nm, which is in agreement with predictions based on
      measurement of differential group delay between the modes. The filter is slightly
      polarization dependent, with a 0.28-nm wavelength difference between the passband
      peaks for the two polarization eigenstates. The optical insertion loss is
      dominated by 2-4-dB bending loss in nonoptimized mode strippers, and the coupling
      loss is negligible. Full acousto-optic mode conversion was achieved at an 8-mW
      electrical input power to the acoustic transducer.

PMID- 19859489
TI  - 91-km attenuation-free transmission with low noise accumulation by use of
      distributed erbium-doped fiber.
AB  - Transparency of a 91-km distributed erbium-doped fiber is achieved with 0.46
      mW/km of pump power at a signal power of -12 d Bm. The accumulation of amplif ier
      noise is measured to be smaller than the minimum noise accumulation that can be
      achieved in a 91-km link with two lumped amplifiers separated by 45 km.

PMID- 19859490
TI  - Correlation of defect centers with photoinduced second-harmonic generation in Er-
      and Sm-doped aluminosilicate fibers.
AB  - The spectral dependence of photoinduced optical losses after chi((2)) writing
      have been obtained in Sm- and Er-doped fibers. The results show that Sm(2+) and
      Er(2+) can be a source of photoelectrons during fiber preparation.

PMID- 19859491
TI  - Low-loss planar optical waveguides in strontium barium niobate crystals formed by
      ion-beam implantation.
AB  - Planar optical waveguides have been formed in strontium barium niobate single
      crystals by either proton or heliumion implantation. The profiles of the ordinary
      and the extraordinary refractive indices are deduced from dark-line mode
      spectroscopy. Optical barriers with depths to Deltan(e) = 2.6% for protons and
      Deltan(e) = 5.5% for helium are obtained. By proton implantation we find a very
      low intensity loss of 0.4 cm(-1) for ordinarily and a higher value of 2.7 cm(-1)
      for extraordinarily polarized light at 632.8 nm. For helium-implanted waveguides
      both values are ~4 cm(-1).

PMID- 19859492
TI  - Synthesis of codirectional couplers with ultralow sidelobes and minimum
      bandwidth.
AB  - A general variational optimization procedure is used to synthesize codirectional
      couplers with arbitrary sidelobe suppression down to -125 dB. Apodization shapes
      yielding sidelobe levels over the range of -40 dB to -75 dB are given by a single
      design formula. The limiting performance in terms of sidelobe suppression versus
      the bandwidth of passive evanescent-type couplers is found.

PMID- 19859493
TI  - Laser characteristics of low-threshold high-efficiency Nd:Sr(5)(VO(4))(3)F
      crystal.
AB  - The absorption spectrum of a new crystal, Nd:Sr(5)(VO(4))(3)F (Nd:S-VAP), was
      measured, which showed that Nd:S-VAP can be suitably pumped at 583.0 and 809.0 nm
      as well as with a xenon f lash lamp. With a tunable dye laser (570-600 nm) and a
      xenon f lash lamp as pump sources, respectively, the free-running and Q-switched
      outputs with BDN dye film were realized at 1.065 microm. For the tunable dye
      laser pump source the threshold energy is 2 mJ and the slope eff iciency is 50%,
      while for the xenon f lash-lamp pump source the lowest threshold energy is 130 mJ
      and the highest slope efficiency is 1.3%. The laser characteristics, such as the
      emission spectrum, the polarization, the output energy, and the pulse width, were
      measured. In addition, the prospect of a Nd:S-VAP crystal for low-threshold, high
      efficiency miniature lasers is discussed.

PMID- 19859494
TI  - Efficient low-energy near-infrared KTiOPO(4) optical parametric converter.
AB  - We report a widely tunable near-infrared holosteric KTiOPO(4) optical parametric
      converter featuring a low pump energy threshold and high conversion efficiency.
      The converter uses two 10-mm-long crystals in a simple optical parametric
      oscillator amplif ier configuration and is tunable from 750 to 1040 nm for the
      signal. The pump energy threshold at 920 nm is 0.44 mJ for the 532-nm 8-ns 50-Hz
      input. The system produces as much as 0.45 mJ of energy at 920 nm with an
      external pump-to-signal energy conversion efficiency of 27% for pump inputs from
      just two times the threshold value. The internal pump-to-signal and idler energy
      conversion efficiency is estimated to be 58%. The low pump energy requirement of
      this system makes it compatible with small laser-diode-pumped solid-state lasers.

PMID- 19859495
TI  - Broadly tunable mid-infrared intracavity difference-frequency laser.
AB  - We generated diffraction-limited laser radiation that is continuously tunable
      from 3.1 to 4.4 microm by mixing the output from a Ti:sapphire laser with the
      intracavity field of a single-frequency, 1.064-microm Nd:YAG ring laser. A peak
      output power of 300 microW was observed near 3.2 microm at a Ti:sapphire input
      power of 300 mW.

PMID- 19859496
TI  - Interface reflection effects in photonic paint.
AB  - Experiments on laser action in scattering systems with gain reveal that even in
      the nondiffusive regime interface reflection effects do not enhance linewidth
      collapse. Instead we show that in dye systems replacing the cell wall with a
      mirror causes broadening and that removing Fresnel reflection at the surface
      results in narrower emission lines.

PMID- 19859497
TI  - All-solid-state continuous-wave tunable blue-light source by intracavity doubling
      of a diode-pumped Cr:LiSAF laser.
AB  - We describe a diode-pumped cw Cr(3+):LiSrAlF(6) laser that produces 190-mW cw
      output at 860 nm. By frequency doubling in a KNbO(3) crystal we generate 13 mW of
      second-harmonic light tunable from 427 to 443 nm.

PMID- 19859498
TI  - Continuously tunable narrow-band operation of an injection-seeded ring-cavity
      optical parametric oscillator: spectroscopic applications.
AB  - A pulsed beta-barium borate optical parametric oscillator is injection seeded by
      cw diode lasers, yielding continuously tunable narrow-band output at its idler
      wavelength. A notable feature of this optical parametric oscillator is that it
      comprises a simple passive ring cavity with no active control of path length as
      the seed wavelength is scanned. We demonstrate this by recording Doppler-limited
      photoacoustic absorption spectra of acetylene gas and Doppler-free two-photon
      fluorescence spectra of rubidium vapor.

PMID- 19859499
TI  - Difference-frequency generation of tunable mid-infrared radiation in bulk
      periodically poled LiNbO(3).
AB  - A bulk, quasi-periodic phase-matched difference-frequency process is demonstrated
      in field-poled LiNbO(3). Continuous tunability of output radiation in the 3.0-4.1
      microm wavelength range is achieved through grating rotation. A maximum mid
      infrared output power of 0.5 mW is measured.

PMID- 19859500
TI  - Semimonolithic Nd:YAG ring resonator for generating cw single-frequency output at
      1.06 microm.
AB  - We report 2.1 W of unidirectional single-frequency laser output from a novel
      Nd:YAG ring laser longitudinally pumped by a laser diode bar. The resonator
      requires only a single discrete optic and magnet, in addition to the laser
      medium, for stable multiwatt single-frequency operation. Undoped YAG is diffusion
      bonded to the Nd:YAG laser crystal at the pump face to eliminate residual spatial
      hole burning and improve thermal conductivity. This new laser design can be
      scaled to higher powers through more facile diode access and is useful for cw
      intracavity doubling.

PMID- 19859501
TI  - Effect of frequency chirp on soliton spectral sidebands in fiber lasers.
AB  - Fiber lasers emit soliton pulses that exhibit discrete spectral sidebands
      generated through dispersive-wave resonances. The position of these soliton
      sidebands is shown to be affected by the amount of chirp acquired by the pulse,
      and the degree of chirp is determined by total cavity losses and gain dispersion.
      Our results show that the soliton chirp shifts the sideband frequencies and that
      sidebands can be generated even in the case of normal dispersion. The long- and
      short-cavity cases are discussed separately so that our results are applicable to
      all laser configurations.

PMID- 19859502
TI  - All-solid-state femtosecond source at 1.55 microm.
AB  - We report on a stretched-pulse additive-pulse mode-locked erbium-doped fiber
      laser pumped by a masteroscillator/power-amplifier diode at 980 nm. This laser
      operates at 1.55 microm and puts out as much as 90 mW of average power at 40 MHz
      with pulse widths that are prism compensated to less than 90 fs. Amplitude jitter
      is less than 0.1%.

PMID- 19859503
TI  - Tunable multiterahertz beat signal generation from a two-wavelength laser-diode
      array.
AB  - We report, for the first time to our knowledge, generation of a tunable
      miltiterahertz modulation signal on an optical carrier directly from a single
      laser source. The modulation frequency, which can be tuned from 0.15 THz to more
      than 7 THz, is the beat note obtained by varying the spectral separation between
      the coaxial two-color output of a two-wavelength laser-diode array from 0.32 to
      17 nm. The frequency characteristics of the terahertz beat note are determined
      with a noncollinear intensity autocorrelator.

PMID- 19859504
TI  - Mode locking in semiconductor lasers by phase-conjugate optical feedback.
AB  - We show theoretically through computer simulations that phase-conjugate optical
      feedback that is realized through four-wave mixing can produce mode locking in
      multilongitudinal-mode semiconductor lasers. Phase-conjugate feedback, in
      contrast to ordinary optical feedback, directly couples pairs of longitudinal
      modes. For certain strengths of phase-conjugate reflectivities, the phases and
      beat frequencies of various longitudinal modes become locked in such a way that
      the laser produces ultrashort mode-locked pulses, even though the laser is pumped
      continuously.

PMID- 19859505
TI  - Simple equations used to study the wavelengths of two-segment bistable diode
      lasers.
AB  - The physical fact that the competition between modes in homogeneously broadened
      media will eventually settle the overall gain down to the threshold level has
      been turned into an extra equation for the mathematical study of the wavelength
      dependent rate equations applicable to two-segment bistable diode lasers. This
      has made the simultaneous determination of bistable laser operation parameters
      including the wavelength much simpler. Calculations of laser wavelength indicate
      that the switch-on and switch-off processes are accompanied by upward and
      downward wavelength chirps, respectively.

PMID- 19859506
TI  - Time-frequency imaging of a single ultrashort light pulse from angularly resolved
      autocorrelation.
AB  - A new technique to measure the frequency-resolved temporal image of a single
      ultrashort light pulse is presented. This technique is based on a single-shot
      self-diffraction autocorrelator in which the pulse duration is related to the
      spatial width of a diffracted beam, the pulse spectrum is related to its
      divergence, and the pulse chirp appears as a curvature of the diffracted-beam
      wave front. An analysis of wave-front curvature by means of a slit diaphragm and
      a cylindrical lens results in a time-frequency image of the initial pulse when a
      spectrometer is not used. This image gives a simple intuitive picture of the
      chirp and the phase modulation of a pulse.

PMID- 19859507
TI  - Kerr-lens mode-locked diode-pumped Cr:LiSGAF laser.
AB  - We have demonstrated stable and self-sustaining Kerr-lens mode locking of a
      Cr:LiSGAF laser pumped by AlGaInP laser diodes. A hard aperture near one end of
      the laser provides the necessary amplitude modulation. This allsolid- state
      system generates transform-limited 100-fs pulses, tunable from 810 to 860 nm. The
      average power at 830 nm is 35 mW, with fluctuations of much less than 1%. The
      thermal properties of Cr:LiSGAF will permit scaling of these results to higher
      power.

PMID- 19859508
TI  - Phase-encoded input joint transform correlator with improved pattern
      discriminability.
AB  - The concept of using phase-encoded input representation in a joint transform
      correlator is presented, in which we show that the phase-encoded input joint
      transform correlator is an optimal filtering system that improves detection
      efficiency and pattern discriminability.

PMID- 19859509
TI  - Demonstration of a nonmagnetic blazed-grating atomic beam splitter.
AB  - We demonstrate a coherent atomic beam splitter for metastable helium atoms, based
      on the diffraction of atomic matter waves from a blazed phase grating. The beam
      splitter is created by driving the two transitions of a three-level V system with
      differentially detuned standing light waves that have a relative spatial phase
      shift of pi/2. The light f ields create a potential that is approximately
      triangular as a function of position in the laser field. Splittings of 38 times
      the photon momentum have been observed.

PMID- 19859510
TI  - Dynamics of statistically inhomogeneous speckles: a new type of manifestation of
      the Doppler effect.
AB  - The diffraction of a focused Gaussian beam from a moving random phase screen is
      discussed. The correlation function of intensity fluctuations of statistically
      inhomogeneous dynamic speckles is studied. A theoretical and experimental
      analysis of the peculiarities of a new type of manifestation of the Doppler
      effect for focused Gaussian beam scattering is carried out.

PMID- 19859511
TI  - Squeezed light from second-harmonic generation: experiment versus theory.
AB  - We report excellent quantitative agreement between theoretical predictions and
      experimental observation of squeezing from a singly resonant second-harmonic
      generating crystal. Limitations in the noise suppression imposed by the pump
      laser are explicitly modeled and confirmed by our measurements.

PMID- 19859512
TI  - Fixing of photorefractive volume holograms in K(1-y)Li(y)Ta(1-x)O(3).
AB  - We report the fixing of photorefractive holographic gratings with high efficiency
      in a sample of K(1-y)Li(y)Ta(1-x)Nb(x)O(3) doped with Cu, V, and Ti. Holograms
      are thermally fixed through the screening of a photorefractive space-charge f
      ield by a nonphotoactive species at elevated temperatures. Fixed holograms are
      revealed by illumination at lower temperatures. Diffraction efficiencies of 25%
      in a 0.54-cm-thick sample are measured. Holograms undergo thermal decay with a
      0.67-eV activation energy.

PMID- 19859513
TI  - Confirmation of the local nature of the plasma grating photorefractive effect.
AB  - Two-wave mixing measurements made during the encoding of plasma gratings in
      AlGaAs:Te indicate that there is no phase shift between the illumination
      intensity pattern and the encoded refractive-index grating. These results support
      our previously proposed photorefractive mechanism, which is based on persistent
      plasma gratings and does not require charge transport.

PMID- 19859514
TI  - Volume holographic image storage and electro-optical readout in a polymer
      dispersed liquid-crystal film.
AB  - We report storage and electrical switching of holographic image data in an
      economical polymer-dispersed liquidcrystal material. The hologram is recorded in
      a fast, single-step process and can be reversibly erased and restored repeatedly
      by the application of fields of approximately 10-15 V/ microm, with a response
      time of 22 micros and a relaxation time of 42 micros. Simple (quasi-sinusoidal)
      holographic transmission gratings also are studied with switching fields of <5 V/
      microm and with response and relaxation times of 25 and 44 micros, respectively.

PMID- 19859515
TI  - Optically switched volume holographic elements.
AB  - We optically switched the diffraction efficiency of volume holographic elements
      recorded in DMP-128 photopolymer by use of a thermal nonlinearity of the liquid
      crystal 5CB. The liquid crystal was incorporated into the volume grating. The
      diffraction efficiency of small areas of the grating was switched with a control
      beam power of several milliwatts. The intensity of a signal beam at a different
      wavelength and arbitrary power was switched with time constants below 1 ms.

PMID- 19859516
TI  - Depth-resolved holographic imaging through scattering media by photorefraction.
AB  - A depth-resolved near-infrared imaging system has been demonstrated for recording
      three-dimensional images of objects embedded in diffuse media. Time-gated
      holographic imaging employing rhodium-doped barium titanate as the recording
      medium is used to acquire whole depth-resolved two-dimensional images in 1 s.
      Millimeter depth resolution has been achieved with a transverse resolution of ~
      30 microm.

PMID- 19859517
TI  - Holographic fixing, readout, and storage dynamics in photorefractive materials.
AB  - Holographic gratings in photorefractive crystals that are based on charge
      redistribution inevitably decay as a result of ionic and electronic conduction.
      Under certain and restricted conditions these decay times can be acceptably long.
      Relevant decay rates and transient hologram field expressions are derived with
      special reference to LiNbO(3). Some experimental data are presented.

PMID- 19859518
TI  - Characterization of fluid flow velocity by optical Doppler tomography.
AB  - The spatial profiles of fluid flow velocity in transparent glass and turbid
      collagen conduits are measured by optical Doppler tomography (ODT). The flow
      velocity at a discrete user-specified spatial location in the conduit is
      determined by measurement of the Doppler shift of backscattered light from
      microspheres suspended in the flowing fluid. Experimental data and theoretical
      calculations are in excellent agreement. ODT is an accurate method for the
      characterization of high-resolution fluid flow velocity.

PMID- 19859519
TI  - Simultaneous interrogation of interferometric and Bragg grating sensors.
AB  - We propose a new method for the simultaneous interrogation of conventional two
      beam interferometers and Bragg grating sensors. The technique employs an
      unbalanced Mach-Zehnder interferometer illuminated by a single low-coherence
      source, which acts as a wavelength-tunable source for the grating and as a path
      matched f ilter for the Fizeau interferometer, thus providing a high phase
      resolution output for each sensor. The grating sensor demonstrates a dynamic
      strain resolution of ~0.05 microepsilon/ radicalHz at 20 Hz, while the
      interferometric phase resolution is better than 1 mrad/ radicalHz at 20 Hz,
      corresponding to an rms mirror displacement of 0.08 nm.

PMID- 19859520
TI  - Multichannel acousto-optic correlator that uses a low-coherence source.
AB  - We describe a time-integrating acousto-optic correlator that allows several
      channels to be multiplexed optically by means of a coherence-multiplexed
      superluminescent laser diode. Parallel channels are generated by birefringent
      electro-optic modulators set in cascade to induce optical path differences
      greater than the coherence length of the source. The system can be combined with
      most of the other previously reported multichannel techniques used in acousto
      optic processors.

PMID- 19859521
TI  - Tension increase correlated to refractive-index change in fibers containing UV
      written Bragg gratings.
AB  - A strong axial tension increase induced by UV laser radiation is observed in the
      cores of single-mode optical fibers containing Bragg gratings, independently of
      the initial core stress. The induced index modulation of the gratings is linearly
      correlated to stress changes with a slope of (0.8 +/- 0.2) x 10(-4) mm(2)/kg. The
      phenomenon can be explained by a structural change of the glass in the fiber core
      into a more compact configuration.

PMID- 19859522
TI  - All-dielectric high-efficiency reflection gratings made with multilayer thin-film
      coatings.
AB  - We made a high-efficiency ref lection grating by coating a nine-layer quarter
      wave system of ZnS/Na(3)AlF(6) directly onto a surface-relief grating in
      photoresist. Eff iciencies of 70% and 84% were measured at the firstorder Littrow
      mount with the laser beam incident from the air side and from the substrate side,
      respectively. The experimental results are in qualitative agreement with
      theoretical predictions. The key to further improvement in the diffraction eff
      iciency is to improve the contour conformation of the coated dielectric layers.

PMID- 19859523
TI  - Global conformational dynamics of a Y-family DNA polymerase during catalysis.
AB  - Replicative DNA polymerases are stalled by damaged DNA while the newly discovered
      Y-family DNA polymerases are recruited to rescue these stalled replication forks,
      thereby enhancing cell survival. The Y-family DNA polymerases, characterized by
      low fidelity and processivity, are able to bypass different classes of DNA
      lesions. A variety of kinetic and structural studies have established a minimal
      reaction pathway common to all DNA polymerases, although the conformational
      intermediates are not well defined. Furthermore, the identification of the rate
      limiting step of nucleotide incorporation catalyzed by any DNA polymerase has
      been a matter of long debate. By monitoring time-dependent fluorescence resonance
      energy transfer (FRET) signal changes at multiple sites in each domain and DNA
      during catalysis, we present here a real-time picture of the global
      conformational transitions of a model Y-family enzyme: DNA polymerase IV (Dpo4)
      from Sulfolobus solfataricus. Our results provide evidence for a hypothetical DNA
      translocation event followed by a rapid protein conformational change prior to
      catalysis and a subsequent slow, post-chemistry protein conformational change.
      Surprisingly, the DNA translocation step was induced by the binding of a correct
      nucleotide. Moreover, we have determined the directions, rates, and activation
      energy barriers of the protein conformational transitions, which indicated that
      the four domains of Dpo4 moved in a synchronized manner. These results showed
      conclusively that a pre-chemistry conformational change associated with domain
      movements was too fast to be the rate-limiting step. Rather, the rearrangement of
      active site residues limited the rate of correct nucleotide incorporation.
      Collectively, the conformational dynamics of Dpo4 offer insights into how the
      inter-domain movements are related to enzymatic function and their concerted
      interactions with other proteins at the replication fork.

PMID- 19859524
TI  - Light directs zebrafish period2 expression via conserved D and E boxes.
AB  - For most species, light represents the principal environmental signal for
      entraining the endogenous circadian clock. The zebrafish is a fascinating
      vertebrate model for studying this process since unlike mammals, direct exposure
      of most of its tissues to light leads to local clock entrainment. Importantly,
      light induces the expression of a set of genes including certain clock genes in
      most zebrafish cell types in vivo and in vitro. However, the mechanism linking
      light to gene expression remains poorly understood. To elucidate this key
      mechanism, here we focus on how light regulates transcription of the zebrafish
      period2 (per2) gene. Using transgenic fish and stably transfected cell line-based
      assays, we define a Light Responsive Module (LRM) within the per2 promoter. The
      LRM lies proximal to the transcription start site and is both necessary and
      sufficient for light-driven gene expression and also for a light-dependent
      circadian clock regulation. Curiously, the LRM sequence is strongly conserved in
      other vertebrate per2 genes, even in species lacking directly light-sensitive
      peripheral clocks. Furthermore, we reveal that the human LRM can substitute for
      the zebrafish LRM to confer light-regulated transcription in zebrafish cells. The
      LRM contains E- and D-box elements that are critical for its function. While the
      E-box directs circadian clock regulation by mediating BMAL/CLOCK activity, the D
      box confers light-driven expression. The zebrafish homolog of the thyrotroph
      embryonic factor binds efficiently to the LRM D-box and transactivates
      expression. We demonstrate that tef mRNA levels are light inducible and that
      knock-down of tef expression attenuates light-driven transcription from the per2
      promoter in vivo. Together, our results support a model where a light-dependent
      crosstalk between E- and D-box binding factors is a central determinant of per2
      expression. These findings extend the general understanding of the mechanism
      whereby the clock is entrained by light and how the regulation of clock gene
      expression by light has evolved in vertebrates.

PMID- 19859525
TI  - Species-specific heterochromatin prevents mitotic chromosome segregation to cause
      hybrid lethality in Drosophila.
AB  - Postzygotic reproductive barriers such as sterility and lethality of hybrids are
      important for establishing and maintaining reproductive isolation between
      species. Identifying the causal loci and discerning how they interfere with the
      development of hybrids is essential for understanding how hybrid
      incompatibilities (HIs) evolve, but little is known about the mechanisms of how
      HI genes cause hybrid dysfunctions. A previously discovered Drosophila
      melanogaster locus called Zhr causes lethality in F1 daughters from crosses
      between Drosophila simulans females and D. melanogaster males. Zhr maps to a
      heterochromatic region of the D. melanogaster X that contains 359-bp satellite
      repeats, suggesting either that Zhr is a rare protein-coding gene embedded within
      heterochromatin, or is a locus consisting of the noncoding repetitive DNA that
      forms heterochromatin. The latter possibility raises the question of how
      heterochromatic DNA can induce lethality in hybrids. Here we show that hybrid
      females die because of widespread mitotic defects induced by lagging chromatin at
      the time during early embryogenesis when heterochromatin is first established.
      The lagging chromatin is confined solely to the paternally inherited D.
      melanogaster X chromatids, and consists predominantly of DNA from the 359-bp
      satellite block. We further found that a rearranged X chromosome carrying a
      deletion of the entire 359-bp satellite block segregated normally, while a
      translocation of the 359-bp satellite block to the Y chromosome resulted in
      defective Y segregation in males, strongly suggesting that the 359-bp satellite
      block specifically and directly inhibits chromatid separation. In hybrids
      produced from wild-type parents, the 359-bp satellite block was highly stretched
      and abnormally enriched with Topoisomerase II throughout mitosis. The 359-bp
      satellite block is not present in D. simulans, suggesting that lethality is
      caused by the absence or divergence of factors in the D. simulans maternal
      cytoplasm that are required for heterochromatin formation of this species
      specific satellite block. These findings demonstrate how divergence of noncoding
      repetitive sequences between species can directly cause reproductive isolation by
      altering chromosome segregation.

PMID- 19859526
TI  - Recognition of lyso-phospholipids by human natural killer T lymphocytes.
AB  - Natural killer T (NKT) cells are a subset of T lymphocytes with potent
      immunoregulatory properties. Recognition of self-antigens presented by CD1d
      molecules is an important route of NKT cell activation; however, the molecular
      identity of specific autoantigens that stimulate human NKT cells remains unclear.
      Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The
      most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated
      phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the
      head group stimulated only weak responses from human NKT cells. However, lyso
      sphingomyelin, which shares the phosphocholine head group of LPC, also activated
      NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating
      increased cytokine responses by NKT cell clones and by freshly isolated
      peripheral blood lymphocytes. These results demonstrate that human NKT cells
      recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since
      these lyso-phospholipids serve as lipid messengers in normal physiological
      processes and are present at elevated levels during inflammatory responses, these
      findings point to a novel link between NKT cells and cellular signaling pathways
      that are associated with human disease pathophysiology.

PMID- 19859527
TI  - Linking inflammation to natural killer T cell activation.
AB  - Immune activation is often associated with inflammation, but inflammation's role
      in the expansion of antigen-specific immune responses remains unclear. This
      primer focuses on recent findings that show how specific natural killer T cells
      are activated by inflammatory messengers, thus illuminating the cellular and
      molecular links between immunity and inflammation.

PMID- 19859528
TI  - Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by
      protein serotonylation.
AB  - While serotonin (5-HT) co-localization with insulin in granules of pancreatic
      beta-cells was demonstrated more than three decades ago, its physiological role
      in the etiology of diabetes is still unclear. We combined biochemical and
      electrophysiological analyses of mice selectively deficient in peripheral
      tryptophan hydroxylase (Tph1-/-) and 5-HT to show that intracellular 5-HT
      regulates insulin secretion. We found that these mice are diabetic and have an
      impaired insulin secretion due to the lack of 5-HT in the pancreas. The
      pharmacological restoration of peripheral 5-HT levels rescued the impaired
      insulin secretion in vivo. These findings were further evidenced by patch clamp
      experiments with isolated Tph1-/- beta-cells, which clearly showed that the
      secretory defect is downstream of Ca(2+)-signaling and can be rescued by direct
      intracellular application of 5-HT via the clamp pipette. In elucidating the
      underlying mechanism further, we demonstrate the covalent coupling of 5-HT by
      transglutaminases during insulin exocytosis to two key players in insulin
      secretion, the small GTPases Rab3a and Rab27a. This renders them constitutively
      active in a receptor-independent signaling mechanism we have recently termed
      serotonylation. Concordantly, an inhibition of such activating serotonylation in
      beta-cells abates insulin secretion. We also observed inactivation of
      serotonylated Rab3a by enhanced proteasomal degradation, which is in line with
      the inactivation of other serotonylated GTPases. Our results demonstrate that 5
      HT regulates insulin secretion by serotonylation of GTPases within pancreatic
      beta-cells and suggest that intracellular 5-HT functions in various
      microenvironments via this mechanism in concert with the known receptor-mediated
      signaling.

PMID- 19859529
TI  - Lost but not forgotten--the economics of improving patient retention in AIDS
      treatment programs.
AB  - Gregory Bisson and Jeffrey Stringer discuss the implications of a new study
      showing how loss to follow-up affects the effectiveness of a public sector HIV
      program in Cote d'Ivoire.

PMID- 19859530
TI  - The neglected tropical diseases and their devastating health and economic impact
      on the member nations of the Organisation of the Islamic Conference.

PMID- 19859531
TI  - Efficacy of short-course AZT plus 3TC to reduce nevirapine resistance in the
      prevention of mother-to-child HIV transmission: a randomized clinical trial.
AB  - BACKGROUND: Single-dose nevirapine (sdNVP)-which prevents mother-to-child
      transmission of HIV-selects non-nucleoside reverse-transcriptase inhibitor
      (NNRTI) resistance mutations in the majority of women and HIV-infected infants
      receiving it. This open-label, randomised trial examined the efficacy of short
      course zidovudine (AZT) and lamivudine (3TC) with sdNVP in reducing NNRTI
      resistance in mothers, and as a secondary objective, in infants, in a setting
      where sdNVP was standard-of-care. METHODS AND FINDINGS: sdNVP alone, administered
      at the onset of labour and to the infant, was compared to sdNVP with AZT plus
      3TC, given as combivir (CBV) for 4 (NVP/CBV4) or 7 (NVP/CBV7) days, initiated
      simultaneously with sdNVP in labour; their newborns received the same regimens.
      Women were randomised 1ratio1ratio1. HIV-1 resistance was assessed by population
      sequencing at: baseline, 2, and 6 wk after birth. An unplanned interim analysis
      resulted in early stopping of the sdNVP arm. 406 pregnant women were randomised
      and took study medication (sdNVP 74, NVP/CBV4 164, and NVP/CBV7 168). HIV-1
      resistance mutations emerged in 59.2%, 11.7%, and 7.3% of women in the sdNVP,
      NVP/CBV4, and NVP/CBV7 arms by 6 wk postpartum; differences between NVP-only and
      both NVP/CBV arms were significant (p<0.0001), but the difference between
      NVP/CBV4 and NVP/CBV7 was not (p = 0.27). Estimated efficacy comparing combined
      CBV arms with sdNVP was 85.6%. Similar resistance reductions were seen in infants
      who were HIV-infected by their 6-wk visit. CONCLUSIONS: A short course of AZT
      plus 3TC, supplementing maternal and infant sdNVP, reduces emergent NNRTI
      resistance mutations in both mothers and their infants. However, this trial was
      not powered to detect small differences between the CBV arms. TRIAL REGISTRATION:
      www.ClinicalTrials.govNCT 00144183.

PMID- 19859532
TI  - Antiretroviral strategies to prevent mother-to-child transmission of HIV:
      striking a balance between efficacy, feasibility, and resistance.
AB  - Dara Lehman and colleagues discuss a randomized trial that found that adding up
      to a week of twice-daily zidovudine+lamivudine to single-dose nevirapine reduces
      the risk of resistance in mothers and infants.

PMID- 19859533
TI  - A word of caution against the stigma trend in neglected tropical disease research
      and control.

PMID- 19859534
TI  - The global burden of trachoma: a review.
AB  - Trachoma is the commonest infectious cause of blindness worldwide. Recurrent
      infection of the ocular surface by Chlamydia trachomatis, the causative agent,
      leads to inturning of the eyelashes (trichiasis) and blinding corneal
      opacification. Trachoma is endemic in more than 50 countries. It is currently
      estimated that there are about 1.3 million people blind from the disease and a
      further 8.2 million have trichiasis. Several estimates for the burden of disease
      from trachoma have been made, giving quite variable results. The variation is
      partly because different prevalence data have been used and partly because
      different sequelae have been included. The most recent estimate from the WHO
      placed it at around 1.3 million Disability-Adjusted Life Years (DALYs). A key
      issue in producing a reliable estimate of the global burden of trachoma is the
      limited amount of reliable survey data from endemic regions.

PMID- 19859535
TI  - A pilot study for control of hyperendemic cystic hydatid disease in China.
AB  - BACKGROUND: Cystic hydatid disease (CHD) is a global parasitic zoonosis caused by
      the dog tapeworm, Echinococcus granulosus. The disease is hyperendemic in western
      China because of poor economic development; limited community knowledge of CHD;
      widespread, small-scale household animal production; home killing of livestock;
      and the feeding of dogs with uncooked offal. METHODOLOGY/PRINCIPAL FINDINGS: A
      control program focusing on monthly praziquantel (PZQ) treatment of all
      registered dogs and culling unwanted and stray dogs has been designed to control
      CHD in hyperendemic areas in China. A pilot field control project in two counties
      (Hutubi and Wensu) in Xinjiang, China showed that after 4 years of treatment, the
      prevalence of dogs with E. granulosus was reduced from 14.7% and 18.6%,
      respectively, to 0%, and this caused a 90%-100% decrease of CHD in sheep born
      after commencement of the control program. CONCLUSIONS/SIGNIFICANCE: The strategy
      aimed at preventing eggs being released from dogs into the environment by
      treating animals before adult tapeworms are patent can decrease E. granulosus
      transmission and considerably reduce hyperendemic CHD. Monthly treatment of dogs
      with PZQ and culling unwanted and stray dogs have been shown to be an efficient,
      highly cost-effective and practicable measure for implementation in rural
      communities. As a result, the Chinese Ministry of Health has launched an
      extensive CHD control program in 117 counties in western China using this control
      strategy.

PMID- 19859536
TI  - Packages of care for alcohol use disorders in low- and middle-income countries.
AB  - In the fourth in a series of six articles on packages of care for mental
      disorders in low- and middle-income countries, Vivek Benegal and colleagues
      discuss the treatment of alcohol use disorders.

PMID- 19859537
TI  - Integrated mapping of neglected tropical diseases: epidemiological findings and
      control implications for northern Bahr-el-Ghazal State, Southern Sudan.
AB  - BACKGROUND: There are few detailed data on the geographic distribution of most
      neglected tropical diseases (NTDs) in post-conflict Southern Sudan. To guide
      intervention by the recently established national programme for integrated NTD
      control, we conducted an integrated prevalence survey for schistosomiasis, soil
      transmitted helminth (STH) infection, lymphatic filariasis (LF), and loiasis in
      Northern Bahr-el-Ghazal State. Our aim was to establish which communities require
      mass drug administration (MDA) with preventive chemotherapy (PCT), rather than to
      provide precise estimates of infection prevalence. METHODS AND FINDINGS: The
      integrated survey design used anecdotal reports of LF and proximity to water
      bodies (for schistosomiasis) to guide selection of survey sites. In total, 86
      communities were surveyed for schistosomiasis and STH; 43 of these were also
      surveyed for LF and loiasis. From these, 4834 urine samples were tested for blood
      in urine using Hemastix reagent strips, 4438 stool samples were analyzed using
      the Kato-Katz technique, and 5254 blood samples were tested for circulating
      Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). 4461
      individuals were interviewed regarding a history of 'eye worm' (a proxy measure
      for loiasis) and 31 village chiefs were interviewed regarding the presence of
      clinical manifestations of LF in their community. At the village level,
      prevalence of Schistosoma haematobium and S. mansoni ranged from 0 to 65.6% and
      from 0 to 9.3%, respectively. The main STH species was hookworm, ranging from 0
      to 70% by village. Infection with LF and loiasis was extremely rare, with only
      four individuals testing positive or reporting symptoms, respectively.
      Questionnaire data on clinical signs of LF did not provide a reliable indication
      of endemicity. MDA intervention thresholds recommended by the World Health
      Organization were only exceeded for urinary schistosomiasis and hookworm in a
      few, yet distinct, communities. CONCLUSION: This was the first attempt to use an
      integrated survey design for this group of infections and to generate detailed
      results to guide their control over a large area of Southern Sudan. The approach
      proved practical, but could be further simplified to reduce field work and costs.
      The results show that only a few areas need to be targeted with MDA of PCT, thus
      confirming the importance of detailed mapping for cost-effective control.

PMID- 19859539
TI  - Transient neuronal populations are required to guide callosal axons: a role for
      semaphorin 3C.
AB  - The corpus callosum (CC) is the main pathway responsible for interhemispheric
      communication. CC agenesis is associated with numerous human pathologies,
      suggesting that a range of developmental defects can result in abnormalities in
      this structure. Midline glial cells are known to play a role in CC development,
      but we here show that two transient populations of midline neurons also make
      major contributions to the formation of this commissure. We report that these two
      neuronal populations enter the CC midline prior to the arrival of callosal
      pioneer axons. Using a combination of mutant analysis and in vitro assays, we
      demonstrate that CC neurons are necessary for normal callosal axon navigation.
      They exert an attractive influence on callosal axons, in part via Semaphorin 3C
      and its receptor Neuropilin-1. By revealing a novel and essential role for these
      neuronal populations in the pathfinding of a major cerebral commissure, our study
      brings new perspectives to pathophysiological mechanisms altering CC formation.

PMID- 19859540
TI  - Novel miR390-dependent transacting siRNA precursors in plants revealed by a PCR
      based experimental approach and database analysis.
AB  - TAS loci in plant genomes encode transacting small interfering RNAs (ta-siRNAs)
      that regulate expression of a number of genes. The function of TAS3 precursor in
      Arabidopsis thaliana is controlled by two miR390 target sites flanking two ta
      siARF sequences targeting mRNAs of ARF transcription factors. Cleavage of the 3'
      miR390-site initiates ta-siRNAs biogenesis. Here we describe the new method for
      identification of plant ta-siRNA precursors based on PCR with
      oligodeoxyribonucleotide primers mimicking miR390. The method was found to be
      efficient for dicotiledonous plants, cycads, and mosses. Based on sequences of
      amplified loci and a database analysis, a novel type of miR390-dependent TAS
      sequences was identified in dicots. These TAS loci are characterized by a smaller
      distance between miR390 sites compared to TAS3, a single copy of ta-siARF, and a
      sequence conservation pattern pointing to the possibility that processing of
      novel TAS-like locus is initiated by cleavage of the 5'-terminal miR390 target
      site.

PMID- 19859538
TI  - Cost-effectiveness of preventing loss to follow-up in HIV treatment programs: a
      Cote d'Ivoire appraisal.
AB  - BACKGROUND: Data from HIV treatment programs in resource-limited settings show
      extensive rates of loss to follow-up (LTFU) ranging from 5% to 40% within 6 mo of
      antiretroviral therapy (ART) initiation. Our objective was to project the
      clinical impact and cost-effectiveness of interventions to prevent LTFU from HIV
      care in West Africa. METHODS AND FINDINGS: We used the Cost-Effectiveness of
      Preventing AIDS Complications (CEPAC) International model to project the clinical
      benefits and cost-effectiveness of LTFU-prevention programs from a payer
      perspective. These programs include components such as eliminating ART co
      payments, eliminating charges to patients for opportunistic infection-related
      drugs, improving personnel training, and providing meals and reimbursing for
      transportation for participants. The efficacies and costs of these interventions
      were extensively varied in sensitivity analyses. We used World Health
      Organization criteria of <3x gross domestic product per capita (3x GDP per capita
      = US$2,823 for Cote d'Ivoire) as a plausible threshold for "cost-effectiveness."
      The main results are based on a reported 18% 1-y LTFU rate. With full retention
      in care, projected per-person discounted life expectancy starting from age 37 y
      was 144.7 mo (12.1 y). Survival losses from LTFU within 1 y of ART initiation
      ranged from 73.9 to 80.7 mo. The intervention costing US$22/person/year (e.g.,
      eliminating ART co-payment) would be cost-effective with an efficacy of at least
      12%. An intervention costing US$77/person/year (inclusive of all the components
      described above) would be cost-effective with an efficacy of at least 41%.
      CONCLUSIONS: Interventions that prevent LTFU in resource-limited settings would
      substantially improve survival and would be cost-effective by international
      criteria with efficacy of at least 12%-41%, depending on the cost of
      intervention, based on a reported 18% cumulative incidence of LTFU at 1 y after
      ART initiation. The commitment to start ART and treat HIV in these settings
      should include interventions to prevent LTFU.

PMID- 19859541
TI  - A prospective nested case-control study of Dengue in infants: rethinking and
      refining the antibody-dependent enhancement dengue hemorrhagic fever model.
AB  - BACKGROUND: Dengue hemorrhagic fever (DHF) is the severe and life-threatening
      syndrome that can develop after infection with any one of the four dengue virus
      (DENV) serotypes. DHF occurs almost exclusively in individuals with secondary
      heterologous DENV infections and infants with primary DENV infections born to
      dengue immune mothers. The widely accepted explanation for the pathogenesis of
      DHF in these settings, particularly during infancy, is antibody-dependent
      enhancement (ADE) of DENV infection. METHODS AND FINDINGS: We conducted a
      prospective nested case-control study of DENV infections during infancy. Clinical
      data and blood samples were collected from 4,441 mothers and infants in up to two
      pre-illness study visits, and surveillance was performed for symptomatic and
      inapparent DENV infections. Pre-illness plasma samples were used to measure the
      associations between maternally derived anti-DENV3 antibody-neutralizing and 
      enhancing capacities at the time of DENV3 infection and development of infant
      DHF. The study captured 60 infants with DENV infections across a wide spectrum of
      disease severity. DENV3 was the predominant serotype among the infants with
      symptomatic (35/40) and inapparent (15/20) DENV infections, and 59/60 infants had
      a primary DENV infection. The estimated in vitro anti-DENV3 neutralizing capacity
      at birth positively correlated with the age of symptomatic primary DENV3 illness
      in infants. At the time of symptomatic DENV3 infection, essentially all infants
      had low anti-DENV3 neutralizing activity (50% plaque reduction neutralizing
      titers [PRNT(50)] </=50) and measurable DENV3 ADE activity. The infants who
      developed DHF did not have significantly higher frequencies or levels of DENV3
      ADE activity compared to symptomatic infants without DHF. A higher weight-for-age
      in the first 3 mo of life and at illness presentation was associated with a
      greater risk for DHF from a primary DENV infection during infancy. CONCLUSIONS:
      This prospective nested case-control study of primarily DENV3 infections during
      infancy has shown that infants exhibit a full range of disease severity after
      primary DENV infections. The results support an initial in vivo protective role
      for maternally derived antibody, and suggest that a DENV3 PRNT(50) >50 is
      associated with protection from symptomatic DENV3 illness. We did not find a
      significant association between DENV3 ADE activity at illness onset and the
      development of DHF compared with less severe symptomatic illness. The results of
      this study should encourage rethinking or refinement of the current ADE
      pathogenesis model for infant DHF and stimulate new directions of research into
      mechanisms responsible for the development of DHF during infancy. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00377754.

PMID- 19859542
TI  - Alternative processing of primary microRNA transcripts by Drosha generates 5' end
      variation of mature microRNA.
AB  - BACKGROUND: It is generally believed that the miRNA processing machinery ensures
      the generation of a mature miRNA with a fixed sequence, particularly at its 5'
      end. However, we and others have recently noted that the ends of a given mature
      miRNA are not absolutely fixed, but subject to variation. Neither the
      significance nor the mechanism behind the generation of such miRNA polymorphism
      is understood. miR-142 is an abundantly expressed miRNA in hematopoietic cells
      and exhibits a high frequency of 5' end polymorphism. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we show that a shift in the Drosha processing of pri-miRNA
      generates multiple forms of miR-142s in vivo with differing 5' ends that might
      target different genes. Sequence analysis of several pre-miRNA ends cloned from T
      cells reveals that unlike many other pri-miRNAs that are processed into a single
      pre-miRNA, pri-miR-142 is processed into 3 distinct pre-miR-142s. Dicer
      processing studies suggest that each of the 3 pre-miR-142s is processed into a
      distinct double-stranded miRNA, giving rise to 4 mature miRNA variants that might
      regulate different target gene pools. CONCLUSIONS/SIGNIFICANCE: Thus, alternative
      Drosha processing might be a novel mechanism for diversification of the miRNA
      target gene pool.

PMID- 19859544
TI  - Notch-RBP-J signaling regulates the mobilization and function of endothelial
      progenitor cells by dynamic modulation of CXCR4 expression in mice.
AB  - Bone marrow (BM)-derived endothelial progenitor cells (EPC) have therapeutic
      potentials in promoting tissue regeneration, but how these cells are modulated in
      vivo has been elusive. Here, we report that RBP-J, the critical transcription
      factor mediating Notch signaling, modulates EPC through CXCR4. In a mouse partial
      hepatectomy (PHx) model, RBP-J deficient EPC showed attenuated capacities of
      homing and facilitating liver regeneration. In resting mice, the conditional
      deletion of RBP-J led to a decrease of BM EPC, with a concomitant increase of EPC
      in the peripheral blood. This was accompanied by a down-regulation of CXCR4 on
      EPC in BM, although CXCR4 expression on EPC in the circulation was up-regulated
      in the absence of RBP-J. PHx in RBP-J deficient mice induced stronger EPC
      mobilization. In vitro, RBP-J deficient EPC showed lowered capacities of
      adhering, migrating, and forming vessel-like structures in three-dimensional
      cultures. Over-expression of CXCR4 could at least rescue the defects in vessel
      formation by the RBP-J deficient EPC. These data suggested that the RBP-J
      mediated Notch signaling regulated EPC mobilization and function, at least
      partially through dynamic modulation of CXCR4 expression. Our findings not only
      provide new insights into the regulation of EPC, but also have implications for
      clinical therapies using EPC in diseases.

PMID- 19859543
TI  - Study of human RIG-I polymorphisms identifies two variants with an opposite
      impact on the antiviral immune response.
AB  - BACKGROUND: RIG-I is a pivotal receptor that detects numerous RNA and DNA
      viruses. Thus, its defectiveness may strongly impair the host antiviral immunity.
      Remarkably, very little information is available on RIG-I single-nucleotide
      polymorphisms (SNPs) presenting a functional impact on the host response.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we studied all non-synonymous SNPs of RIG-I
      using biochemical and structural modeling approaches. We identified two important
      variants: (i) a frameshift mutation (P(229)fs) that generates a truncated,
      constitutively active receptor and (ii) a serine to isoleucine mutation
      (S(183)I), which drastically inhibits antiviral signaling and exerts a down
      regulatory effect, due to unintended stable complexes of RIG-I with itself and
      with MAVS, a key downstream adapter protein. CONCLUSIONS/SIGNIFICANCE: Hence,
      this study characterized P(229)fs and S(183)I SNPs as major functional RIG-I
      variants and potential genetic determinants of viral susceptibility. This work
      also demonstrated that serine 183 is a residue that critically regulates RIG-I
      induced antiviral signaling.

PMID- 19859545
TI  - Analysis of pulmonary inflammation and function in the mouse and baboon after
      exposure to Mycoplasma pneumoniae CARDS toxin.
AB  - Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as
      the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been
      shown to be cytotoxic to mammalian cells in tissue and organ culture. In this
      study we tested the ability of recombinant CARDS (rCARDS) toxin to elicit changes
      within the pulmonary compartment in both mice and baboons. Animals responded to a
      respiratory exposure to rCARDS toxin in a dose and activity-dependent manner by
      increasing the expression of the pro-inflammatory cytokines IL-1alpha, 1beta, 6,
      12, 17, TNF-alpha and IFN-gamma. There was also a dose-dependent increase in
      several growth factors and chemokines following toxin exposure including KC, IL
      8, RANTES, and G-CSF. Increased expression of IFN-gamma was observed only in the
      baboon; otherwise, mice and baboons responded to CARDS toxin in a very similar
      manner. Introduction of rCARDS toxin to the airways of mice or baboons resulted
      in a cellular inflammatory response characterized by a dose-dependent early
      vacuolization and cytotoxicity of the bronchiolar epithelium followed by a robust
      peribronchial and perivascular lymphocytic infiltration. In mice, rCARDS toxin
      caused airway hyper-reactivity two days after toxin exposure as well as prolonged
      airway obstruction. The changes in airway function, cytokine expression, and
      cellular inflammation correlate temporally and are consistent with what has been
      reported for M. pneumoniae infection. Altogether, these data suggest that the
      CARDS toxin interacts extensively with the pulmonary compartment and that the
      CARDS toxin is sufficient to cause prolonged inflammatory responses and airway
      dysfunction.

PMID- 19859546
TI  - COP9 limits dendritic branching via Cullin3-dependent degradation of the actin
      crosslinking BTB-domain protein Kelch.
AB  - Components of the COP9 signalosome (CSN), a key member of the conserved 26S
      proteasome degradation pathway, have been detected to be altered in patients of
      several debilitating syndromes. These findings suggest that CSN acts in neural
      circuits, but the exact function of CSN in brain remains unidentified.
      Previously, using Drosophila peripheral nervous system (PNS) as a model system,
      we determined that CSN is a critical regulator of dendritic morphogenesis. We
      found that defects in CSN led to the strikingly contrast phenotype of either
      reducing or stimulating dendritic branching. In particular, we have reported that
      CSN stimulates dendritic branching via Cullin1-mediated proteolysis. Here we
      describe that CSN inhibits dendritic arborization in PNS neurons acting via
      control of Cullin3 function: loss of Cullin3 causes excessive dendritic
      branching. We also identified a downstream target for Cullin3-dependent
      degradation in neurons--the actin-crosslinking BTB-domain protein Kelch.
      Inappropriate accumulation of Kelch, either due to the impaired Cullin3-dependent
      turnover, or ectopic expression of Kelch, leads to uncontrolled dendritic
      branching. These findings indicate that the CSN pathway modulates neuronal
      network in a multilayer manner, providing the foundation for new insight into the
      CSN role in human mental retardation disorders and neurodegenerative disease.

PMID- 19859547
TI  - Differential expression of immune defences is associated with specific host
      parasite interactions in insects.
AB  - Recent ecological studies in invertebrates show that the outcome of an infection
      is dependent on the specific pairing of host and parasite. Such specificity
      contrasts the long-held view that invertebrate innate immunity depends on a broad
      spectrum recognition system. An important question is whether this specificity is
      due to the immune response rather than some other interplay between host and
      parasite genotypes. By measuring the expression of putative bumblebee homologues
      of antimicrobial peptides in response to infection by their gut trypanosome
      Crithidia bombi, we demonstrate that expression differences are associated with
      the specific interactions.

PMID- 19859548
TI  - Post-domestication selection in the maize starch pathway.
AB  - Modern crops have usually experienced domestication selection and subsequent
      genetic improvement (post-domestication selection). Chinese waxy maize, which
      originated from non-glutinous domesticated maize (Zea mays ssp. mays), provides a
      unique model for investigating the post-domestication selection of maize. In this
      study, the genetic diversity of six key genes in the starch pathway was
      investigated in a glutinous population that included 55 Chinese waxy accessions,
      and a selective bottleneck that resulted in apparent reductions in diversity in
      Chinese waxy maize was observed. Significant positive selection in waxy (wx) but
      not amylose extender1 (ae1) was detected in the glutinous population, in complete
      contrast to the findings in non-glutinous maize, which indicated a shift in the
      selection target from ae1 to wx during the improvement of Chinese waxy maize. Our
      results suggest that an agronomic trait can be quickly improved into a target
      trait with changes in the selection target among genes in a crop pathway.

PMID- 19859549
TI  - Proteomic and phospho-proteomic profile of human platelets in basal, resting
      state: insights into integrin signaling.
AB  - During atherogenesis and vascular inflammation quiescent platelets are activated
      to increase the surface expression and ligand affinity of the integrin
      alphaIIbbeta3 via inside-out signaling. Diverse signals such as thrombin, ADP and
      epinephrine transduce signals through their respective GPCRs to activate protein
      kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of
      the integrin alphaIIbbeta3 and augment its function. The signaling pathways that
      transmit signals from the GPCR to the cytosolic domain of the integrin are not
      well defined. In an effort to better understand these pathways, we employed a
      combination of proteomic profiling and computational analyses of isolated human
      platelets. We analyzed ten independent human samples and identified a total of
      1507 unique proteins in platelets. This is the most comprehensive platelet
      proteome assembled to date and includes 190 membrane-associated and 262
      phosphorylated proteins, which were identified via independent proteomic and
      phospho-proteomic profiling. We used this proteomic dataset to create a platelet
      protein-protein interaction (PPI) network and applied novel contextual
      information about the phosphorylation step to introduce limited directionality in
      the PPI graph. This newly developed contextual PPI network computationally
      recapitulated an integrin signaling pathway. Most importantly, our approach not
      only provided insights into the mechanism of integrin alphaIIbbeta3 activation in
      resting platelets but also provides an improved model for analysis and discovery
      of PPI dynamics and signaling pathways in the future.

PMID- 19859551
TI  - Impact of the Pro12Ala polymorphism of the PPAR-Gamma 2 gene on metabolic and
      clinical characteristics in the Palestinian type 2 diabetic patients.
AB  - Peroxisome proliferators activated receptor-gamma2 (PPARgamma2) represents the
      transcriptional master regulator of adipocyte differentiation and therefore has
      been suggested as a candidate gene for obesity, insulin resistance, and
      dyslipidemia. The objective of the study was to investigate for the first time
      the potential association of the most common variant Pro12Ala (p.P12A)
      substitution of the PPARgamma2 gene with body mass index (BMI), blood pressure,
      fasting plasma glucose, plasma total cholesterol, LDL and HDL cholesterol, and
      plasma triglyceride in a sample of 202 (138 females and 64 male) type 2 diabetic
      Palestinians. Genotyping of the PPARgamma2 p.P12A polymorphism was determined by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. The A12 allele was associated with lower fasting plasma glucose (P =
      .03) but had no influence on blood pressure, BMI, or other metabolic parameters.
      In obese patients, the p.P12A substitution was associated with elevated total
      plasma cholesterol levels (P = .02) and a tendency toward increased LDL
      cholesterol level (P = .06). In conclusion, the p.P12A variant of the PPARgamma2
      may influence cardiovascular risk through effects on lipid metabolism in obese
      T2D Palestinian patients.

PMID- 19859550
TI  - Quantitative assessment of stereotyped and challenged locomotion after lesion of
      the striatum: a 3D kinematic study in rats.
AB  - BACKGROUND: Although the striatum is in position to regulate motor function, the
      role of the structure in locomotor behaviour is poorly understood. Therefore, a
      detailed analysis of locomotion- and obstacle avoidance-related parameters was
      performed after unilateral lesion of the striatum in rats. METHODS AND RESULTS:
      Using the three dimensional motion capture technology, kinematics of walking and
      clearing obstacles, head and body orientation were analyzed before and up to 60
      days after the lesion. Recordings were performed in treadmill running rats with
      or without obstacles attached to the treadmill belt. The lesion, which was
      induced by the direct injection of the mitochondrial toxin malonate into the left
      caudoputamen resulted in the complete destruction of the dorsal striatum. During
      the first three days following the lesion, rats were unable to run on the
      treadmill. Thereafter, rats showed normal looking locomotion, yet the
      contralesional limbs exhibited changes in length and timing parameters, and were
      overflexed. Moreover, the head of lesioned rats was orientated towards the side
      of the lesion, and their postural vertical shifted towards the contralesional
      side. During obstructed running, the contralesional limbs when they were leading
      the crossing manoeuvre stepped on the obstacle rather than to overcome obstacle
      without touching it, yet more frequently with the forelimb than the hindlimb.
      Unsuccessful crossings appeared to be due to a paw placement farther away from
      the front of the obstacles, and not to an inappropriate limb elevation.
      Importantly, deficit in locomotor behaviour did not regress over the time.
      CONCLUSION: Our results argue that the striatum of one hemisphere controls
      kinematics of contralateral limbs during stereotyped locomotion and plays a
      prominent role in the selection of the right motor program so that these limbs
      successfully cross over obstacle.

PMID- 19859552
TI  - Polymer Brushes Containing Sulfonated Sugar Repeat Units: Synthesis,
      Characterization and In Vitro Testing of Blood Coagulation Activation.
AB  - A new polymer brush chemistry containing sulfonated carbohydrate repeat units has
      been synthesized from silicon substrates using ATRP methods and characterized
      both in bulk and using surface analysis. The polymer brush was designed to act as
      a mimic for the naturally occurring sulfonated glycosaminoglycan, heparin,
      commonly used for modifying blood-contacting surfaces both in vitro and in vivo.
      Surface analysis showed conversion of brush saccharide precursor chemistry to the
      desired sulfonated polymer product. The sulfonated polymer brush surface was
      further analyzed using three conventional in vitro tests for blood compatibility 
      - plasma recalcification times, complement activation, and thrombin generation.
      The sulfonated polymer brush films on silicon oxide wafers exhibited better assay
      performance in these blood component assays than the unsulfonated sugar
      functionalized polymer brush in all tests performed.

PMID- 19859553
TI  - A significant increase of RNAi efficiency in human cells by the CMV enhancer with
      a tRNAlys promoter.
AB  - RNA interference (RNAi) is the process of mRNA degradation induced by double
      stranded RNA in a sequence-specific manner. Different types of promoters, such as
      U6, H1, tRNA, and CMV, have been used to control the inhibitory effect of RNAi
      expression vectors. In the present study, we constructed two shRNA expression
      vectors, respectively, controlled by tRNA(lys) and CMV enhancer-tRNA(lys)
      promoters. Compared to the vectors with tRNA(lys) or U6 promoter, the vector with
      a CMV enhancer-tRNA(lys) promoter silenced pokemon more efficiently on both the
      mRNA and the protein levels. Meanwhile, the silencing of pokemon inhibited the
      proliferation of MCF7 cells, but the induction of apoptosis of MCF7 cells was not
      observed. We conclude that the CMV enhancer-tRNA(lys) promoter may be a powerful
      tool in driving intracellular expression of shRNA which can efficiently silence
      targeted gene.

PMID- 19859554
TI  - How to reach a common estimate of high dietary micronutrient intakes for safe
      addition of vitamins and minerals to foods?
AB  - BACKGROUND: A central element in establishing maximum amount of micronutrients in
      fortified foods and supplements is to reach to an agreement on how to estimate
      high intakes of vitamins and minerals from the European diet. OBJECTIVE: To
      examine whether ratios between the 95th percentile and mean intakes of vitamins
      and minerals show similarities across different countries independent of dietary
      habits and survey methods and if so, to suggest a simple and pragmatic way to
      calculate common estimates of high micronutrient intakes from foods. DESIGN:
      Intake data of selected vitamins and minerals from nine European countries were
      examined for adult females and males and for children aged 4-10 and 11-17 years.
      The ratios between the 95th percentile and mean intakes were calculated for each
      micronutrient, country, and age group. RESULTS: The ratios for each micronutrient
      follow a fairly regular pattern across countries and survey methods with
      differences between age groups. THE NUTRIENTS FALL INTO THREE CATEGORIES:
      nutrients with ratios between 1.45 and 1.58 - energy, magnesium, phosphorus,
      zinc, iron, vitamin B(6), niacin, and folate; nutrients with ratios between 1.67
      and 1.79 - calcium, selenium, vitamin E, iodine, and copper; nutrients with
      ratios between 2.08 and 2.32 - vitamin A, vitamin D, and retinol. CONCLUSION:
      Sufficiently precise estimates of high micronutrient intakes across European
      countries can be reached by multiplying the overall average of ratios (P95/mean
      intakes) for each micronutrient with the corresponding mean intakes from all
      available dietary surveys in Europe. This approach is a simple and pragmatic way
      to create common European estimates of high micronutrient intakes from foods.

PMID- 19859555
TI  - Microrna-221 and microrna-222 modulate differentiation and maturation of skeletal
      muscle cells.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs that have
      recently emerged as important regulators of gene expression. They negatively
      regulate gene expression post-transcriptionally by translational repression and
      target mRNA degradation. miRNAs have been shown to play crucial roles in muscle
      development and in regulation of muscle cell proliferation and differentiation.
      METHODOLOGY/PRINCIPAL FINDINGS: By comparing miRNA expression profiling of
      proliferating myoblasts versus differentiated myotubes, a number of modulated
      miRNAs, not previously implicated in regulation of myogenic differentiation, were
      identified. Among these, miR-221 and miR-222 were strongly down-regulated upon
      differentiation of both primary and established myogenic cells. Conversely, miR
      221 and miR-222 expression was restored in post-mitotic, terminally
      differentiated myotubes subjected to Src tyrosine kinase activation. By the use
      of specific inhibitors we provide evidence that expression of miR-221 and miR-222
      is under the control of the Ras-MAPK pathway. Both in myoblasts and in myotubes,
      levels of the cell cycle inhibitor p27 inversely correlated with miR-221 and miR
      222 expression, and indeed we show that p27 mRNA is a direct target of these
      miRNAs in myogenic cells. Ectopic expression of miR-221 and miR-222 in myoblasts
      undergoing differentiation induced a delay in withdrawal from the cell cycle and
      in myogenin expression, followed by inhibition of sarcomeric protein
      accumulation. When miR-221 and miR-222 were expressed in myotubes undergoing
      maturation, a profound alteration of myofibrillar organization was observed.
      CONCLUSIONS/SIGNIFICANCE: miR-221 and miR-222 have been found to be modulated
      during myogenesis and to play a role both in the progression from myoblasts to
      myocytes and in the achievement of the fully differentiated phenotype.
      Identification of miRNAs modulating muscle gene expression is crucial for the
      understanding of the circuits controlling skeletal muscle differentiation and
      maintenance.

PMID- 19859556
TI  - Extreme cranial ontogeny in the upper cretaceous dinosaur pachycephalosaurus.
AB  - BACKGROUND: Extended neoteny and late stage allometric growth increase
      morphological disparity between growth stages in at least some dinosaurs. Coupled
      with relatively low dinosaur density in the Upper Cretaceous of North America,
      ontogenetic transformational representatives are often difficult to distinguish.
      For example, many hadrosaurids previously reported to represent relatively small
      lambeosaurine species were demonstrated to be juveniles of the larger taxa.
      Marginocephalians (pachycephalosaurids + ceratopsids) undergo comparable and
      extreme cranial morphological change during ontogeny. METHODOLOGY/PRINCIPAL
      FINDINGS: Cranial histology, morphology and computer tomography reveal patterns
      of internal skull development that show the purported diagnostic characters for
      the pachycephalosaurids Dracorex hogwartsia and Stygimoloch spinifer are
      ontogenetically derived features. Coronal histological sections of the
      frontoparietal dome of an adult Pachycephalosaurus wyomingensis reveal a dense
      structure composed of metaplastic bone with a variety of extremely fibrous and
      acellular tissue. Coronal histological sections and computer tomography of a
      skull and frontoparietal dome of Stygimoloch spinifer reveal an open intrafrontal
      suture indicative of a subadult stage of development. These dinosaurs employed
      metaplasia to rapidly grow and change the size and shape of their horns, cranial
      ornaments and frontoparietal domes, resulting in extreme cranial alterations
      during late stages of growth. We propose that Dracorex hogwartsia, Stygimoloch
      spinifer and Pachycephalosaurus wyomingensis are the same taxon and represent an
      ontogenetic series united by shared morphology and increasing skull length.
      CONCLUSIONS/SIGNIFICANCE: Dracorex hogwartsia (juvenile) and Stygimoloch spinifer
      (subadult) are reinterpreted as younger growth stages of Pachycephalosaurus
      wyomingensis (adult). This synonymy reduces the number of pachycephalosaurid taxa
      from the Upper Cretaceous of North America and demonstrates the importance of
      cranial ontogeny in evaluating dinosaur diversity and taxonomy. These growth
      stages reflect a continuum rather than specific developmental steps defined by
      "known" terminal morphologies.

PMID- 19859557
TI  - A chemokine targets the nucleus: Cxcl12-gamma isoform localizes to the nucleolus
      in adult mouse heart.
AB  - Chemokines are extracellular mediators of complex regulatory circuits involved
      principally in cell-to-cell communication. Most studies to date of the essential
      chemokine Cxcl12 (Sdf-1) have focused on the ubiquitously expressed secreted
      isoforms alpha and beta. Here we show that, unlike these isoforms and all other
      known chemokines, the alternatively transcribed gamma isoform is an intracellular
      protein that localizes to the nucleolus in differentiated mouse Cardiac tissue.
      Our results demonstrate that nucleolar transportation is encoded by a nucleolar
      localization signal in the unique carboxy-terminal region of Sdf-1gamma, and is
      competent both in vivo and in vitro. The molecular mechanism underlying these
      unusual chemokine properties involves cardiac-specific transcription of an mRNA
      containing a unique short-leader sequence lacking the signal peptide and
      translation from a non-canonical CUG codon. Our results provide an example of
      genome economy even for essential and highly conserved genes such as Cxcl12, and
      suggest that chemokines can exert tissue specific functions unrelated to cell-to
      cell communication.

PMID- 19859558
TI  - Combination PPARgamma and RXR Agonist Treatment in Melanoma Cells: Functional
      Importance of S100A2.
AB  - Nuclear hormone receptors, including RXR and PPARgamma, represent novel
      therapeutic targets in melanoma. We have previously shown that the DRO subline of
      the amelanotic melanoma A375 responds to rexinoid and thiazolidinedione (TZD)
      treatment in vitro and in vivo. We performed microarray analysis of A375(DRO)
      after TZD and combination rexinoid/TZD treatment in which the calcium binding
      protein S100A2 had increased expression after rexinoid or TZD treatment and a
      synergistic increase to combination treatment. Increased S100A2 expression is
      dependent on an intact PPARgamma receptor, but it is not sufficient to mediate
      the antiproliferative effects of rexinoid/TZD treatment. Over expression of
      S100A2 enhanced the effect of rexinoid and TZD treatment while inhibition of
      S100A2 expression attenuated the response to rexinoid/TZD treatment, suggesting
      that S100A2 is necessary for optimal response to RXR and PPARgamma activation by
      respective ligands. In summary, we have identified potential downstream mediators
      of rexinoid and TZD treatment in a poorly differentiated melanoma and found that
      alterations in S100A2 expression affect RXR and PPARgamma signaling in A375(DRO)
      cells. These studies provide insight into potential mechanisms of tumor response
      or resistance to these novel therapies.

PMID- 19859559
TI  - Has culling been properly assessed as a valid and justified control intervention
      measure for zoonotic diseases?

PMID- 19859560
TI  - A randomized trial assessing the safety and immunogenicity of AS01 and AS02
      adjuvanted RTS,S malaria vaccine candidates in children in Gabon.
AB  - BACKGROUND: The malaria vaccine candidate antigen RTS,S includes parts of the pre
      erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface
      antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in
      water emulsion--based formulation (AS02) and a formulation based on liposomes
      (AS01). METHODS & PRINCIPAL FINDINGS: In this Phase II, double-blind study
      (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were
      randomized to receive either RTS,S/AS01(E) or RTS,S/AS02(D), on a 0-1-2 month
      vaccination schedule. The children were followed-up daily for six days after each
      vaccination and monthly for 14 months. Blood samples were collected at 4 time
      points. Both vaccines were well tolerated. Safety parameters were distributed
      similarly between the two groups. Both vaccines elicited a strong specific immune
      response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D)/AS01(E))
      of 0.88 (95% CI: 0.68-1.15) post-Dose 3. After Doses 2 and 3 of experimental
      vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been
      previously vaccinated with at least one dose of hepatitis B vaccine compared to
      those not previously vaccinated. CONCLUSIONS: RTS,S/AS01(E) proved similarly as
      well tolerated and immunogenic as RTS,S/AS02(D), completing an essential step in
      the age de-escalation process within the RTS,S clinical development plan. TRIAL
      REGISTRATION: ClinicalTrials.gov. NCT00307021.

PMID- 19859561
TI  - Toxoplasma gondii inhibits covalent modification of histone H3 at the IL-10
      promoter in infected macrophages.
AB  - Infection of macrophages with the protozoan parasite Toxoplasma gondii results in
      inhibition of a large panel of LPS-responsive cytokines, including TNF-alpha,
      while leaving others such as IL-10 intact. Recent studies provide evidence that
      the parasite interferes with chromatin remodeling at the TNF-alpha promoter that
      is normally associated with LPS stimulation, but that is not required for TLR4
      induction of IL-10. Here, we examined the effect of Toxoplasma on IL-10 induced
      by simultaneous signaling through TLR4 and FcgammaR, a combined stimulus that
      triggers histone H3 covalent modification at the IL-10 promoter resulting in high
      level IL-10 cytokine production. We show that the parasite inhibits high level IL
      10 production and prevents histone H3 Ser(10) phosphorylation and Lys(9/14)
      acetylation at the IL-10 promoter. These results provide compelling evidence that
      T. gondii targets the host cell chromatin remodeling machinery to down-regulate
      cytokine responses in infected macrophages.

PMID- 19859562
TI  - The quantity and quality of African children's IgG responses to merozoite surface
      antigens reflect protection against Plasmodium falciparum malaria.
AB  - BACKGROUND: Antibodies, particularly cytophilic IgG subclasses, with specificity
      for asexual blood stage antigens of Plasmodium falciparum, are thought to play an
      important role in acquired immunity to malaria. Evaluating such responses in
      longitudinal sero-epidemiological field studies, allied to increasing knowledge
      of the immunological mechanisms associated with anti-malarial protection, will
      help in the development of malaria vaccines. METHODS AND FINDINGS: We conducted a
      1-year follow-up study of 305 Senegalese children and identified those resistant
      or susceptible to malaria. In retrospective analyses we then compared post-follow
      up IgG responses to six asexual-stage candidate malaria vaccine antigens in
      groups of individuals with clearly defined clinical and parasitological histories
      of infection with P. falciparum. In age-adjusted analyses, children resistant to
      malaria as well as to high-density parasitemia, had significantly higher IgG1
      responses to GLURP and IgG3 responses to MSP2 than their susceptible
      counterparts. Among those resistant to malaria, high anti-MSP1 IgG1 levels were
      associated with protection against high-density parasitemia. To assess functional
      attributes, we used an in vitro parasite growth inhibition assay with purified
      IgG. Samples from individuals with high levels of IgG directed to MSP1, MSP2 and
      AMA1 gave the strongest parasite growth inhibition, but a marked age-related
      decline was observed in these effects. CONCLUSION: Our data are consistent with
      the idea that protection against P. falciparum malaria in children depends on
      acquisition of a constellation of appropriate, functionally active IgG subclass
      responses directed to multiple asexual stage antigens. Our results suggest at
      least two distinct mechanisms via which antibodies may exert protective effects.
      Although declining with age, the growth inhibitory effects of purified IgG
      measurable in vitro reflected levels of anti-AMA1, -MSP1 and -MSP2, but not of
      anti-GLURP IgG. The latter could act on parasite growth via indirect
      parasiticidal pathways.

PMID- 19859564
TI  - NeuroMath: advanced methods for the estimation of human brain activity and
      connectivity.

PMID- 19859563
TI  - GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors.
AB  - The Ewing Sarcoma Family Tumors (ESFT) consist of the classical pathologic
      entities of Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor.
      Occurring largely in the childhood through young adult years, these tumors have
      an unsurpassed propensity for metastasis and have no defined cell of origin. The
      biology of these aggressive malignancies centers around EWS/FLI1 and related
      EWS/ETS chimeric transcription factors, which are largely limited to this tumor
      class. Much progress has been made in the identification of a network of loci
      whose expression is modulated by EWS/FLI1 and its congeners. To date, little
      progress has been made in reconstructing the sequence of direct and indirect
      events that produce this network of modulated loci. The recent identification of
      GLI1 as an upregulated target of EWS/ETS transcription factors suggests a target
      which may be a more central mediator in the ESFT signaling network. In this
      paper, we further define the relationship of EWS/FLI1 expression and GLI1
      upregulation in ESFT. This relationship is supported with data from primary tumor
      specimens. It is consistently observed across multiple ESFT cell lines and with
      multiple means of EWS/FLI1 inhibition. GLI1 inhibition affects tumor cell line
      phenotype whether shRNA or endogenous or pharmacologic inhibitors are employed.
      As is seen in model transformation systems, GLI1 upregulation by EWS/FLI1 appears
      to be independent of Hedgehog stimulation. Consistent with a more central role in
      ESFT pathogenesis, several known EWS/FLI1 targets appear to be targeted through
      GLI1. These findings further establish a central role for GLI1 in the
      pathogenesis of Ewing Tumors.

PMID- 19859565
TI  - The use of a Meckel's diverticulum in the creation of an orthotopic neobladder in
      case of a short mesoileum: a case report.
AB  - A 72-year-old patient was treated in our department for an invasive bladder TCC
      by cystoprostatectomy with the intention to create an orthotopic neobladder.
      During surgery it appeared to be impossible to mobilize part of the preterminal
      ileum into the small pelvis to make an anastomosis with the urethral stump.
      However, incidentally, a Meckel's diverticulum of about 8 cm was found on the
      preterminal ileum which could easily be mobilized onto the urethral stump. The
      intestinal insertion of the diverticulum served as the lowest point of the pouch.
      Above the diverticulum, we created a modified Studer-pouch. No major
      postoperative complications occurred and during the follow-up period of more than
      12 months micturition was good.

PMID- 19859566
TI  - Influence of overt diabetes mellitus on cyclosporine pharmacokinetics in a canine
      model.
AB  - BACKGROUND/AIMS: Diabetic patients usually require more medications than their
      nondiabetic counterparts. This work examined the effect of hyperglycemia on the
      pharmacokinetic properties of cyclosporine in a diabetic dog model. MAIN METHODS:
      Diabetes was induced using a streptozotocin/alloxan combination and verified by
      measuring the serum glucose level. Cyclosporine was administered as a bolus
      intravenous dose of 5 mg/kg, and blood samples were collected at different time
      points for determining drug concentrations and biochemical analyses. RESULTS:
      Diabetic dogs showed a significant increase in total body clearance of
      cyclosporine compared to healthy controls (0.457 L hr(-1)Kg(-1) versus 0.201 L
      hr(-1)Kg(-1), P = .0019) and a decrease in its biological half-life (9.32 hours
      versus 22.56 hours, P = .0125). In addition, diabetic animals exhibited a higher
      total cholesterol (7.20 +/- 0.62 mmol/L and 5.28 +/- 0.36 mmol/L; P < .05) as
      well as more serum low density lipoproteins (4.45 +/- 0.72 mmol/L versus 1.06 +/-
      0.10 mmol/L; P < .05). CONCLUSION: Overt diabetes alters cyclosporine disposition
      by modulating its clearance. Abnormalities in the lipid profile, among other
      factors, may contribute to the accelerated metabolic degradation of cyclosporine
      under hyperglycemic conditions.

PMID- 19859567
TI  - Protective effect of melatonin against mitomycin C-induced genotoxic damage in
      peripheral blood of rats.
AB  - Mitomycin C (MMC) generates free radicals when metabolized. We investigated the
      effect of melatonin against MMC-induced genotoxicity in polychromatic
      erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates.
      Rats (N = 36) were classified into 4 groups: control, melatonin, MMC, and MMC +
      melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were
      injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48,
      72, and 96 hours posttreatment and homogenates were obtained at 96 hours
      posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE)
      per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA) plus 4
      hydroxyalkenal (4-HDA) levels were used as an index of lipid peroxidation. The
      MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours
      that was significantly reduced with melatonin begin coadministrated. No
      significant differences were found in lipid peroxidation. Our results indicate
      that MMC-induced genotoxicity can be reduced by melatonin.

PMID- 19859568
TI  - Timing of locomotor activity circadian rhythms in Caenorhabditis elegans.
AB  - Circadian rhythms are driven by endogenous biological clocks and are synchronized
      to environmental cues. The chronobiological study of Caenorhabditis elegans, an
      extensively used animal model for developmental and genetic research, might
      provide fundamental information about the basis of circadian rhythmicity in
      eukaryotes, due to its ease of use and manipulations, as well as availability of
      genetic data and mutant strains. The aim of this study is to fully characterize
      the circadian rhythm of locomotor activity in C. elegans, as well as a means for
      genetic screening in this nematode and the identification of circadian mutants.
      We have developed an infrared method to measure locomotor activity in C. elegans
      and found that, under constant conditions, although inter-individual variability
      is present, circadian periodicity shows a population distribution of periods
      centered at 23.9+/-0.4 h and is temperature-compensated. Locomotor activity is
      entrainable by light-dark cycles and by low-amplitude temperature cycles, peaking
      around the night-day transition and day, respectively. In addition, lin-42(mg152)
      or lin-42(n1089) mutants (bearing a mutation in the lin-42 gene, homolog to the
      per gene) exhibit a significantly longer circadian period of 25.2+/-0.4 h or
      25.6+/-0.5 h, respectively. Our results represent a complete description of the
      locomotor activity rhythm in C. elegans, with a methodology that allowed us to
      uncover three of the key features of circadian systems: entrainment, free-running
      and temperature compensation. In addition, abnormal circadian periods in clock
      mutants suggest a common molecular machinery responsible for circadian
      rhythmicity. Our analysis of circadian rhythmicity in C. elegans opens the
      possibility for further screening for circadian mutations in this species.

PMID- 19859569
TI  - Physiological function of mycobacterial mtFabD, an essential malonyl-CoA:AcpM
      transacylase of type 2 fatty acid synthase FASII, in yeast mct1Delta cells.
AB  - Mycobacterium tuberculosis mtFabD is an essential malonyl-CoA:AcpM transacylase
      and is important for vital protein-protein interactions within type 2 fatty acid
      synthase FASII. mtFabD contacts KasA, KasB, FabH, InhA, and possibly also HadAB,
      HadBC, and FabG1/MabA. Disruption of mtFabD's interactions during FASII has been
      proposed for drug development. Here, the gene for a mitochondrially targeted
      mtFabD was ectopically expressed in Saccharomyces cerevisiae mct1Delta mutant
      cells lacking the corresponding mitochondrial malonyl-CoA transferase Mct1p,
      allowing the mutants to recover their abilities to respire on glycerol and
      synthesize lipoic acid. Hence, mtFabD could physiologically function in an
      environment lacking holo-AcpM or other native interaction partners.

PMID- 19859571
TI  - Crossmodal links between vision and touch in spatial attention: a computational
      modelling study.
AB  - Many studies have revealed that attention operates across different sensory
      modalities, to facilitate the selection of relevant information in the multimodal
      situations of every-day life. Cross-modal links have been observed either when
      attention is directed voluntarily (endogenous) or involuntarily (exogenous). The
      neural basis of cross-modal attention presents a significant challenge to
      cognitive neuroscience. Here, we used a neural network model to elucidate the
      neural correlates of visual-tactile interactions in exogenous and endogenous
      attention. The model includes two unimodal (visual and tactile) areas connected
      with a bimodal area in each hemisphere and a competition between the two
      hemispheres. The model is able to explain cross-modal facilitation both in
      exogenous and endogenous attention, ascribing it to an advantaged activation of
      the bimodal area on the attended side (via a top-down or bottom-up biasing), with
      concomitant inhibition towards the opposite side. The model suggests that a
      competitive/cooperative interaction with biased competition may mediate both
      forms of cross-modal attention.

PMID- 19859570
TI  - Functional characterization of N-terminally GFP-tagged GLP-1 receptor.
AB  - The glucagon-like peptide-1 receptor (GLP-1 receptor) mediates important effects
      on peripheral tissues and the central nervous system. It seems one of the most
      promising therapeutic targets for treatment of diabetes mellitus type 2.
      Surprisingly, very little is known about the cellular mechanisms that regulate
      its function in vivo. One of the approaches to study receptor dynamics,
      expression, or signaling is using GFP-tagged fluorescent proteins. In this study,
      we synthesized and characterized N-terminally GFP-tagged GLP-1 (GFP-GLP-1)
      receptor in CHO cells. We demonstrated that GFP-GLP-1 receptor is weakly
      expressed in the plasma membranes and is functionally coupled to adenylyl cyclase
      via heterotrimeric G-proteins, similarly as its wild type.

PMID- 19859572
TI  - Benefit of whole pelvic radiotherapy combined with neoadjuvant androgen
      deprivation for the high-risk prostate cancer.
AB  - AIM: To study whether use of neoadjuvant androgen deprivation therapy (N-ADT)
      combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer
      patients was associated with survival benefit over prostate radiotherapy (PORT)
      only. MATERIAL AND METHODS: Between 1999 and 2004, 162 high-risk prostate cancer
      patients were treated with radiotherapy combined with long-term androgen
      deprivation therapy (L-ADT). Patients were prospectively assigned into two
      groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts.
      RESULTS: The 5-year actuarial overall survival (OS) rates were 89% for A and 78%
      for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A
      = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates
      were 52% versus 40% (P = .07), for groups A and B, respectively. CONCLUSIONS: The
      WPRT combined with N-ADT compared to PORT for high-risk patients resulted in
      improvement in CSS and bPFS; however no OS benefit was observed.

PMID- 19859573
TI  - An exon-based comparative variant analysis pipeline to study the scale and role
      of frameshift and nonsense mutation in the human-chimpanzee divergence.
AB  - Chimpanzees and humans are closely related but differ in many deadly human
      diseases and other characteristics in physiology, anatomy, and pathology. In
      spite of decades of extensive research, crucial questions about the molecular
      mechanisms behind the differences are yet to be understood. Here I report
      ExonVar, a novel computational pipeline for Exon-based human-chimpanzee
      comparative Variant analysis. The objective is to comparatively analyze mutations
      specifically those that caused the frameshift and nonsense mutations and to
      assess their scale and potential impacts on human-chimpanzee divergence.
      Genomewide analysis of human and chimpanzee exons with ExonVar identified a
      number of species-specific, exon-disrupting mutations in chimpanzees but much
      fewer in humans. Many were found on genes involved in important biological
      processes such as T cell lineage development, the pathogenesis of inflammatory
      diseases, and antigen induced cell death. A "less-is-more" model was previously
      established to illustrate the role of the gene inactivation and disruptions
      during human evolution. Here this analysis suggested a different model where the
      chimpanzee-specific exon-disrupting mutations may act as additional evolutionary
      force that drove the human-chimpanzee divergence. Finally, the analysis revealed
      a number of sequencing errors in the chimpanzee and human genome sequences and
      further illustrated that they could be corrected without resequencing.

PMID- 19859574
TI  - Two Cases of Retroperitoneal Liposarcoma Diagnosed Using Endoscopic Ultrasound
      Guided Fine-Needle Aspiration (EUS-FNA).
AB  - This report describes our experience with two cases that were ultimately
      diagnosed as retroperitoneal liposarcoma using endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA). Case 1 is that of a 54-year-old woman with chief
      complaints of nausea and abdominal distention. Computed tomography (CT) and
      magnetic resonance imaging (MRI) revealed a large (15 cm diameter) tumor, which
      was significantly compressing the stomach and apparently occupied the entire left
      abdominal cavity. Although advanced primary gastrointestinal stromal tumor (GIST)
      or retroperitoneal tumor was inferred as the differential diagnosis, a definitive
      diagnosis was difficult using imaging alone. After EUS-FNA was done, the tumor
      was diagnosed histopathologically as high-grade liposarcoma. Case 2 is that of a
      73-year-old man. Abdominal ultrasonography and CT showed a 6 cm diameter tumor
      within the pelvic cavity. The tumor had high MRI signal-intensity on both T1 and
      T2 images. Endorectal EUS showed a hyperechoic mass. The images suggested lipoma
      or liposarcoma containing lipoma-like components. Myxoid liposarcoma was revealed
      by subsequent EUS-FNA. Performing EUS-FNA was clinically useful for determining
      the subsequent therapeutic strategy in these cases where a tumor of unknown
      origin existed in the retroperitoneum.

PMID- 19859576
TI  - Hybrid mammogram classification using rough set and fuzzy classifier.
AB  - We propose a computer aided detection (CAD) system for the detection and
      classification of suspicious regions in mammographic images. This system combines
      a dimensionality reduction module (using principal component analysis), a feature
      extraction module (using independent component analysis), and a feature subset
      selection module (using rough set model). Rough set model is used to reduce the
      effect of data inconsistency while a fuzzy classifier is integrated into the
      system to label subimages into normal or abnormal regions. The experimental
      results show that this system has an accuracy of 84.03% and a recall percentage
      of 87.28%.

PMID- 19859577
TI  - Deformation twinning in Ni-Mn-Ga micropillars with 10M martensite.
AB  - The maximum actuation frequency of magnetic shape-memory alloys (MSMAs)
      significantly increases with decreasing size of the transducer making MSMAs
      interesting candidates for small scale actuator applications. To study the
      mechanical properties of Ni-Mn-Ga single crystals on small length scales, two
      single-domain micropillars with dimensions of 10x15x30 mum(3) were fabricated
      from a Ni-Mn-Ga monocrystal using dual beam focused ion beam machining. The
      pillars were oriented such that the crystallographic c direction was
      perpendicular to the loading direction. The pillars were compressed to maximum
      stresses of 350 and 50 MPa, respectively. Atomic force microscopy and magnetic
      force microscopy were performed prior to fabrication of the pillars and following
      the deformation experiments. Both micropillars were deformed by twinning as
      evidenced by the stress-strain curve. For one pillar, a permanent deformation of
      3.6% was observed and ac twins (10M martensite) were identified after unloading.
      For the other pillar, only 0.7% remained upon unloading. No twins were found in
      this pillar after unloading. The recovery of deformation is discussed in the
      light of pseudoelastic twinning and twin-substrate interaction. The twinning
      stress was higher than in similar macroscopic material. However, further studies
      are needed to substantiate a size effect.

PMID- 19859578
TI  - Surface acoustic wave propagation in Y- and Z-cut 0.67PbMgNbO(3)-0.33PbTiO(3)
      single crystals.
AB  - Surface acoustic wave (SAW) propogation in Y-cut and Z-cut relaxor-based
      0.67Pb(Mg(13)Nb(23))O(3)-0.33PbTiO(3) (PMN-33%PT) ferroelectric single crystals
      poled along [001](c) cubic direction has been analyzed theoretically.
      Characteristic curves were obtained for the phase velocity, electromechanical
      coupling coefficient and PFA of SAW in Y-cut and Z-cut PMN-33%PT single crystals.
      It was found that the phase velocity is lower, while the electromechanical
      coupling coefficient is much higher, than that of traditional piezoelectric
      materials. The power flow angle (PFA) can be zero in certain directions, which
      makes this crystal system a promising material for future SAW devices with
      smaller size and enhanced performance. The directions near 45 degrees and 135
      degrees of Y-cut PMN-33%PT crystals are found to be optimum directions for SAW
      device applications.

PMID- 19859579
TI  - Structure of YSi(2) nanowires from scanning tunneling spectroscopy and first
      principles.
AB  - Exceptionally long and uniform YSi(2) nanowires are formed via self-assembly on
      Si(001). The in-plane width of the thinnest wires is known to be quantized in odd
      multiples of the silicon lattice constant. Here, we identify a class of nanowires
      that violates the "odd multiple" rule. The structure of the thinnest wire in this
      category is determined by comparing scanning tunneling spectroscopy measurements
      with the calculated surface density of states of candidate models by means of the
      Pendry R-factor analysis. The relative stability of the odd and even wire systems
      is analyzed via first-principles calculations.

PMID- 19859580
TI  - Observation of polarization-gate based reconstruction quality improvement during
      the process of turbidity suppression by optical phase conjugation.
AB  - We present experiments that study the impact of polarization selection on the
      phenomenon of turbidity suppression by optical phase conjugation. Counter to
      intuition, we discovered that the preferential utilization of multiply scattered
      light field components over their sparsely scattered counterparts via appropriate
      polarization selection can lead to better image reconstruction quality. This
      effect was observed with tissue phantoms and biological tissue sections. The
      physical origin of this effect and its dependence on scatterer properties are
      discussed.

PMID- 19859581
TI  - Repeated Intraperitoneal alpha-Radioimmunotherapy of Ovarian Cancer in Mice.
AB  - The aim of this study was to investigate the therapeutic efficacy of alpha
      radioimmunotherapy of ovarian cancer in mice using different fractionated
      treatment regimens. The study was performed using the monoclonal antibody MX35
      F(ab')(2) labeled with the alpha-particle emitter (211)At. Methods. Nude mice
      were intraperitoneally inoculated with ~1 x 10(7) cells of the cell line
      NIH:OVCAR-3. Four weeks later 6 groups of animals were given 400 kBq (211)At-MX35
      F(ab')(2) as a single or as a repeated treatment of up to 6 times (n = 18 in each
      group). The fractionated treatments were given every seventh day. Control animals
      were treated with unlabeled MX35 F(ab')(2) (n = 12). Eight weeks posttreatment
      the animals were sacrificed and the presence of macro- and microscopic tumors and
      ascites was determined. Results. The tumor-free fractions (TFFs) of the animals,
      defined as the fraction of animals with no macro- and microtumors and no ascites,
      were 0.17, 0.11, 0.39, 0.44, 0.44, and 0.67 when treated with 400 kBq (211)At
      MX35 F(ab')(2) once or 2, 3, 4, 5, or 6 times, respectively. Repeated treatment 3
      times or more resulted in a significantly higher (P < .05) TFF than compared to
      treatment once or twice. The presence of ascites decreased from 15 out of 18
      animals in the group given only one treatment to zero for the 2 groups given 5 or
      6 fractions. Treatment with unlabeled MX35 F(ab')(2) resulted in a TFF of zero.
      Conclusion. Weekly repeated intraperitoneal injections of tolerable amounts of
      activity of (211)At-MX35 F(ab')(2) of up to 6 times produced increased
      therapeutic efficacy without observed toxicity, indicating a potential increase
      of the therapeutic index.

PMID- 19859582
TI  - Psychogenic nonepileptic seizures after head injury: a case report.
AB  - Psychogenic nonepileptic seizures (PNESs) are diagnosed when disruptive changes
      in behaviour, thinking, or emotion resemble epileptic seizures (ESs), but no
      paroxysmal discharges are seen on electroencephalogram (EEG) and do not originate
      from another medical illness. The gold standard for PNES diagnosis is video
      electroencephalogram (Video-EEG). PNESs are defined by modern psychiatry as
      conversion and dissociative disorders but these disorders may coexist with many
      others psychiatric disorders, including depression, posttraumatic stress
      disorder, and personality disorders. It is well known that epileptic seizures are
      a frequent and well-studied complication of traumatic head injury (THI). However,
      THI may also generate psychic symptoms including PNES. In this paper we describe
      a patient who developed PNES after THI in a bus accident and received a diagnosis
      of refractory epilepsy for 24 years until she underwent Video-EEG.

PMID- 19859583
TI  - When should surgical cytoreduction in advanced ovarian cancer take place?
AB  - Initial surgical management is commonly accepted to date as paramount in the
      treatment of women presenting with epithelial ovarian cancer and permits the
      assessment of the disease (staging), the histological confirmation of disease
      type and grade, and the practice of maximal debulking preceding platinum-based
      chemotherapy. Many studies have shown that the volume of residual disease after
      initial surgical cytoreduction inversely correlates with survival. Thus, women
      with optimal debulking performed by a trained specialist have improved median
      survival. In this review, we will focus on the answers gleaned from clinical
      trials on primary and interval surgery, which prompts the question on the timing
      of surgery in respect to chemotherapy. Interval debulking surgery (IDS) is
      secondary cytoreduction following primary debulking and is carried out in between
      the courses of chemotherapy. The major clinical trials and the latest systematic
      reviews seem unable to give any definitive guidance or recommendation for
      clinical practice. The choice of aggressive primary cytoreduction or upfront
      chemotherapy followed by second line surgical cytoreduction seems among others to
      have to be individualized according to tumour load, prediction of its
      resectability, and response to chemotherapy. The role of tumour biology must also
      be kept in mind. Finally, concrete answers are awaited on the timing of surgery
      from the ongoing prospective randomized control trials (CHORUS and EORTC 55971)
      though preliminary data from the latter have already been presented at major
      meetings (IGCS 2008; SGO 2009) and ignited strong debate.

PMID- 19859584
TI  - B Cell IgD Deletion Prevents Alveolar Bone Loss Following Murine Oral Infection.
AB  - Periodontal disease is one of the most common infectious diseases of humans.
      Immune responses to infection trigger loss of alveolar bone from the jaw and
      eventual tooth loss. We investigated the contribution of B cell IgD to alveolar
      bone loss by comparing the response of B cell normal BALB/cJ mice and IgD
      deficient BALB/c-Igh-5(-/-J) mice to oral infection with Porphyromonas
      gingivalis, a gram-negative periodontopathic bacterium from humans. P. gingivalis
      infected normal mice lost bone. Specific antibody to P. gingivalis was lower and
      oral colonization was higher in IgD deficient mice; yet bone loss was completely
      absent. Infection increased the proportion of CD69(+) activated B cells and
      CD4(+) T cells in immune normal mice compared to IgD deficient mice. These data
      suggest that IgD is an important mediator of alveolar bone resorption, possibly
      through antigen-specific coactivation of B cells and CD4(+) T cells.

PMID- 19859587
TI  - Metal nanoparticles or metal oxide nanoparticles, an efficient and promising
      family of novel heterogeneous catalysts in organic synthesis.
AB  - Recently, organic reactions catalyzed by metal/metal oxide nanoparticles (NPs)
      has attracted much attention. The notable advantages of this novel family of
      heterogeneous catalysts, such as high catalytic activity, good recyclability and
      improved selectivity, extend to a wide-range of applications in various organic
      reactions. This perspective provides an overview of the progresses made in
      metal/metal oxide NPs catalyzed organic reactions achieved in our group. Based on
      our investigations, we suggest that further exploration is required in two
      aspects in this area: (1) the effects of the size and shape of NPs on the
      reaction activity and selectivity, and (2) the effect of the supporting
      environment of the artificial template on the reaction activity and selectivity.

PMID- 19859588
TI  - Molecular water-oxidation catalysts for photoelectrochemical cells.
AB  - Photoelectrochemical cells that efficiently split water into oxygen and hydrogen,
      "the fuel of the future", need to combine robust water oxidation catalysts at the
      anode (2H(2)O --> O(2) + 4H(+) + 4e(-)) with hydrogen reduction catalysts at the
      cathode (2H(+) + 2e(-)--> H(2)). Both sets of catalysts will, ideally, operate at
      low overpotentials and employ light-driven or light-assisted processes. In this
      Perspective article, we focus on significant efforts to develop solid state
      materials and molecular coordination complexes as catalyst for water oxidation.
      We briefly review the field with emphasis on the various molecular catalysts that
      have been developed and then examine the activity of molecular catalysts in water
      oxidation following their attachment to conducting electrodes. For such molecular
      species to be useful in a solar water-splitting device it is preferable that they
      are securely and durably affixed to an electrode surface. We also consider recent
      developments aimed at combining the action of molecular catalysts with light
      absorption so that light driven water oxidation may be achieved.

PMID- 19859589
TI  - Self-assembly of star-shaped heteropoly-15-palladate(II).
AB  - A novel heteropolyoxopalladate structural type has been discovered: the polyoxo
      15-palladate(II) [Pd(0.4)Na(0.6) subsetPd(15)P(10)O(50)H(6.6)](12-) (Pd(15)) has
      been prepared in a one-pot self-assembly reaction and characterized by single
      crystal XRD, elemental analysis, IR, TGA, (31)P NMR and electrochemistry;
      preliminary catalytic studies showed that Pd(15) is active as a catalyst in
      alcohol oxidation by dioxygen.

PMID- 19859590
TI  - Novel luminescent iminephosphine complex of copper(I) with high photochemical and
      electrochemical stability.
AB  - Luminescent heteroleptic Cu(I) complexes based on asymmetrical iminephosphine
      ligands exhibit improved electrochemical and photochemical stability as compared
      to the analogous complexes based on traditional diimine or diphosphine ligands.

PMID- 19859591
TI  - A tetranuclear molecular rectangle from four gold(I) atoms linked by dicarbene
      and diphosphine ligands.
AB  - A tetranuclear molecular rectangle consisting of two bridging dicarbene ligands
      and two bridging diphosphine ligands was prepared by connection of two dinuclear
      gold(I) complexes with 1,2-bis(diphenylphosphino)ethane.

PMID- 19859592
TI  - Access to new magnetic cores in Fe(III) and Fe(III)/Cu(II) spin clusters.
AB  - The synthesis, structure and magnetic properties of
      [Fe(14)O(4)(OH)(4)(H(2)L)(2)(HL)(4)(piv)(20)] (1) and
      [Fe(8)Cu(2)O(4)(H(2)L)(4)(HL)(2)(OBz)(12)] (2) are reported (H(3)L = 2-amino-2
      (hydroxymethyl)propane-1,3-diol): both complexes have unique core structures and
      display non-zero spin ground states.

PMID- 19859594
TI  - Tri-, tetra- and octa-metallic vanadium(III) clusters from new, simple starting
      materials: interplay of exchange and anisotropy effects.
AB  - The crystal structure of the monomeric vanadium(III) species mer
      [V(bipy)Cl(3)(MeCN)] (1; bipy = 2,2'-bipyridine) is reported. The solvothermal
      reaction of [V(bipy)Cl(3)(MeCN)]with Na(O(2)CPh) yields the T-shaped cluster
      [V(3)(O)Cl(3)(O(2)CPh)(2)(bipy)(2)(OEt)(2)], magnetic studies of which show
      strong intramolecular antiferromagnetic coupling giving a well isolated S = 1
      ground state. Solvothermal treatment of 1 with triols yields a series of
      polymetallic clusters [V(4)Cl(6)(thme)(2)(bipy)(3)],
      [V(3)Cl(4)(Hcht)(2)(bipy)(2)]Cl and
      [V(8)(OH)(2)Cl(4)(cht)(4)(O(2)CPh)(6)(bipy)(2)], structurally related to
      previously reported {M(4)} centred triangles. Magnetic studies of this series
      reveal very weak intramolecular antiferromagnetic exchange and very strong local
      zero-field splitting effects.

PMID- 19859593
TI  - EXAFS and DFT: evidence for the [Tc=O]2+ core.
AB  - A structure elucidation strategy combining X-ray Absorption Spectroscopy (XAS)
      and Density Functional Theory (DFT) is demonstrated and reveals the existence of
      the [Tc=O](2+) moiety.

PMID- 19859595
TI  - (Mu-eta2:eta2-disulfido)dinickel(II) complexes supported by 6-methyl-TPA ligands.
AB  - A series of (mu-eta(2):eta(2)-disulfido)dinickel(II) complexes 2(n) have been
      synthesized by the reaction of Na(2)S(2) and nickel(II) complexes 1(n) supported
      by tris[(pyridin-2-yl)methyl]amine (TPA; 1(0)) [(6-methylpyridin-2
      yl)methyl]bis[(pyridin-2-yl)methyl]amine (Me(1)TPA; 1(1)), bis[(6-methylpyridin-2
      yl)methyl][(pyridin-2-yl)methyl]amine (Me(2)TPA; 1(2)) and tris[(6-methylpyridin
      2-yl)methyl]amine (Me(3)TPA; 1(3)), respectively, and characterised by UV-vis and
      resonance Raman spectroscopy. X-ray crystallographic analyses on 2(2) and 2(3)
      supported by Me(2)TPA and Me(3)TPA, respectively, have revealed that the
      Ni(2)S(2) core is largely bent (approximately 30 degrees) along the S-S axis,
      being in sharp contrast to the planar Ni(2)S(2) core structure of the (mu
      eta(2):eta(2)-disulfido)dinickel(II) complexes reported so far. The UV-vis
      spectra of 2(0) and 2(1) supported by TPA and Me(1)TPA, respectively, exhibiting
      an intense absorption band at approximately 360 nm together with a shoulder
      around 400 nm and a weak and broad absorption band around 450-600 nm, are very
      close to those of 2(2) and 2(3), suggesting that 2(0) and 2(1) also exhibit a
      similar distorted Ni(2)S(2) core structure. Resonance Raman spectra of 2(n)
      showed a characteristic S-S stretching vibration mode at approximately 450 cm(-1)
      with an isotope shift Delta nu((32)S-(34)S) = 10-15 cm(-1). The reaction of 2(n)
      with (p-Me-C(6)H(4))(3)P gave (p-Me-C(6)H(4))(3)P=S quantitatively based on 2(n).
      Hammett analysis on the sulfur atom transfer process from 2(n) to the phosphine
      derivatives [(p-X-C(6)H(4))P; X = OMe, Me, H and Cl] has indicated that the
      reaction involves an electrophilic ionic mechanism. Moreover, the order of
      reactivity of 2(n) toward PPh(3) has been found as 2(0) > 2(3) > 2(1) > 2(2). On
      the basis of these results, the ligand effects of Me(n)TPA on the structure and
      reactivity of the nickel(II) complexes have been discussed.

PMID- 19859596
TI  - Synthesis, structure, and magnetic properties of cyanide-bridged low-dimensional
      heterometallic Fe(III)-Mn(II) complexes.
AB  - With trans-dicyanideiron(III) precursor K[Fe(salen)(CN)(2)] x CH(3)OH (1)
      (H(2)salen = N,N'-bis(salicyl)ethylenediamine) as a building block, four new
      cyanide-bridged heterometallic Fe(III)-Mn(II) complexes
      {[Fe(salen)(CN)(2)](2)[Mn(bipy)(2)]} x CH(3)OH x 2 H(2)O (2),
      {[Fe(salen)(CN)(2)](2)[Mn(phen)(2)]} x CH(3)OH (3), and
      {[Fe(salen)(CN)(2)][Mn(L)]}ClO(4) x CH(3)OH [L = L(a) (4) and L(b) (5)] have been
      successfully assembled. Single X-ray diffraction analyses reveals the trinuclear
      Fe(III)(2)Mn(II) nature of complexes 2 and 3 comprised of one
      [Mn(bipy)(2)](2+)/[Mn(phen)(2)](2+) and two [Fe(salen)(CN)(2)](-) units, and the
      one-dimensional cyanide-bridged cationic polymeric single chain nature of
      complexes 4 and 5 consisting of alternating units of [Mn(L)](2+) (L = L(a) and
      L(b)) and [Fe(salen)(CN)(2)](-) with free ClO(4)(-) as balanced anions.
      Investigations into the magnetic properties of these four heterometallic cyanide
      bridged Fe(III)-Mn(II) complexes reveals the overall antiferromagnetic
      interaction between neighbouring Fe(III) and Mn(II) ions through the bridging
      cyanide group. On the basis of the Hamiltonian H = -2JS(Mn)(S(Fe(1)) + S(Fe(2))),
      the magnetic simulation for the trimeric complexes 2 and 3 gives the magnetic
      coupling constant 2J(MnFe) = -2.68(4) cm(-1) for 2 and 2J(MnFe) = -2.46(8) cm(-1)
      for 3, respectively. A best-fit to the magnetic susceptibilities of 4 and 5 based
      on the one-dimensional alternating chain model leads to the magnetic coupling
      constants 2J(1) = -6.50(2) and 2J(2) = -1.57(1) cm(-1) for 4 and 2J(1) = -5.35(2)
      and 2J(2) = -0.93(1) cm(-1) for 5.

PMID- 19859597
TI  - Ordered fabrication of luminescent multilayered thin films of CdSe quantum dots.
AB  - The surface of CdSe nanoparticles was functionalized with 11-hydroxyundecanoic
      acid (11-HUDA) during in situ preparation to afford stable and highly luminescent
      quantum dot (QD) solutions. The reactivity of the hydroxyl groups of 11-HUDA was
      then utilized in carbamate bond forming reactions with diisocyanate-bearing
      molecules that serve as linkers in the fabrication of the multilayered CdSe
      quantum dot films. The covalent bond formation readily proceeds at ambient
      temperature and results in a layer-by-layer formation of thin films comprised of
      photoluminescent CdSe nanoparticles separated by long chain organic connectors.
      The successive layer-by-layer approach can be repeated multiple times to get the
      desired thickness of QD films on glass or silicon substrates. The atomic force
      microscopy indicated the successful attachment of the QDs on the substrate
      surface. Importantly, the in situ functionalized CdSe nanoparticles preserve
      their stable and highly photoluminescent optical properties in the resulting
      multilayered films. Moreover, there is a gradual increase in the intensities of
      electronic absorption and photoluminescent bands of the QDs with increasing the
      number of layers, confirming successful fabrication of the multilayered films.
      The quantum yield (QY) of the 12-layered film was measured to be 6%. These
      findings are important for the development of QD-based optical, electronic and
      sensing devices that can harness the highly photoluminescent properties of these
      ordered and stable nanocomposite materials.

PMID- 19859598
TI  - Metal-ligand cooperation in the trans addition of dihydrogen to a pincer Ir(I)
      complex: a DFT study.
AB  - DFT calculations on the hydrogenation of a (PNP)Ir(I) complex, to give the trans-
      rather then the cis--dihydride isomer, show that the reaction proceeds via a
      deprotonation/protonation of the ligand arm with concomitant
      dearomatization/aromatization of the pyridine core. Thus, the actual H(2)
      activation step occurs by an Ir(III) complex and not by the Ir(I) starting
      complex, as supported by experimental observations. This ligand participation
      allows for products that would otherwise be inaccessible. In addition, trace
      amounts of water, which are likely to be present in the solvent, facilitate
      proton transfer reaction steps.

PMID- 19859599
TI  - Syntheses, crystal structures, thermal stabilities and luminescence of two new
      zinc phosphonates.
AB  - Two new zinc phosphonates, [(C5H14N2)0.5Zn5(HO3PCH(OH)CO2)(O3PCH(OH)CO2)3 x 2
      H2O] x 2 H2O (1) and [(C4H12N2)Zn2(O3PCH(OH)CO2)2] (2), have been synthesized
      under hydrothermal conditions and characterized by single-crystal X-ray
      diffraction along with powder XRD, elemental analysis (EA), IR, and
      thermogravimetric analysis (TGA). In compound 1, [ZnO6] octahedra and [ZnO5]
      square-pyramids are bridged by 2-hydroxyl(phosphono)acetate with tri-, tetra-,
      and pentadentate coordination modes, resulting in a 3D framework possessing 1D 24
      atom channels. In compound 2, 2-hydroxyl(phosphono)acetate exhibits a new
      tridentate coordination mode to link [ZnO4] tetrahedrons into a 2D hybrid layer.
      Both 2-methylpiperazine and piperazine serve as structure-directing agents, which
      are encapsulated into frameworks through electrostatic interactions and hydrogen
      bonding. Solids 1 and 2 display purple and yellow-green emission, respectively.
      It is interesting that solid 1 can give off bright white, yellow and orange-red
      emission under different heat-treatment temperatures. Furthermore, the
      luminescent color of solid 1-250 can be reversibly tuned among yellow-green,
      purple-blue, bright white and blue-green by shifting the wavelength of excited
      light.

PMID- 19859601
TI  - Synthesis and characterization of the titanium complexes bearing two
      regioisomeric trifluoromethyl-containing enaminoketonato ligands and their
      behavior in ethylene polymerization.
AB  - A series of new titanium complexes bearing two regioisomeric trifluoromethyl
      containing enaminoketonato ligands (3a-h and 6a-h), [PhN=CRCHC(CF3)O]2TiCl2 (3a,
      R = Me; 3b, R = n-C5H11; 3c, R = i-Pr; 3d, R = Cy; 3e, R = t-Bu; 3f, R = CH=CHPh;
      3g, R = Et; 3h, R = n-C11H23) and [PhN=C(CF3)CHC(R)O]2TiCl2 (6a, R = Ph; 6b, R =
      n-C5H11; 6c, R = i-Pr; 6d, R = Cy; 6e, R = t-Bu; 6f, R = CH=CHPh; 6g, R = CHPh2;
      6h, R = CF3) have been synthesized and characterized. X-ray crystal structures
      analyses suggest that complexes 3c-e and 6c-d all adopt a distorted octahedral
      geometry around the titanium center. Complexes 3c, 3d and 6c display a cis
      configuration of the two chlorine atoms around the titanium center, while complex
      6d shows a trans-configuration of the two chlorine atoms. Especially, the
      configurational isomers (cis and trans) of complex 3e were identified both in
      solution and in the solid state by NMR and X-ray analyses. With modified
      methylaluminoxane as a cocatalyst, all the complexes are active towards ethylene
      polymerization, and produce high molecular weight polymers. With the variation of
      the relative position of the imino group and the trifluoromethyl group of the
      beta-enaminoketonato ligands, the polymerization behavior of the catalysts
      changed remarkably. It is observed that the substituent directly joined to the
      carbonyl in the ligands plays an important role for both the catalytic activities
      and the properties of the polymers produced.

PMID- 19859600
TI  - A new molybdenum(V) nickel phosphate based on divacant
      [H30(Mo(V)16O32)Ni14(PO4)26O2(OH)4(H2O)8]12- wheel.
AB  - A new molybdenum nickel phosphate,
      [H(2)en](3)Na(4)[Ni(H(2)O)(3)][H(30)(Mo(V)(16)O(32))Ni(14)(PO(4))(26)O(2)
      (OH)(4)(H(2)O)(8)] x 8 H(2)O 1, has been hydrothermally synthesized and
      structurally characterized. Compound 1 crystallizes in the monoclinic space group
      P2(1)/c with a = 18.6118(6) A, b = 20.9879(6) A, c = 22.9360(5) A, beta =
      116.678(2) degrees, V = 8005.5(4) A(3) and Z = 2. The polyoxoanion of 1 exhibits
      an unusual divacant wheel-type cluster in which two {NiO(6)} octahedra are lost
      from the well-known "saturated" {Mo(16)TM(16)P(26)} wheel. The two vacant sites
      are occupied by two protonated ethylenediamines (H(2)en) via the strong hydrogen
      bonding interactions between the surface O atoms of the polyoxoanions and the
      amine group derived from the H(2)en ligands. DC susceptibility measurements show
      that compound 1 exhibits strong antiferromagnetic interactions inside the wheel
      type cluster.

PMID- 19859602
TI  - Relaxation and luminescence studies on hydrated bipyridyl- and terpyridyl-based
      lanthanide complexes.
AB  - The synthesis of the novel ligand L2, based on a 2,2'-bipyridine functionalized
      by a carboxylate function and a methyleneiminodiacetate group in positions 6 and
      6', is described. Its europium complex, [EuL2(H(2)O)(3)], has been prepared and
      characterized. The spectroscopic properties of [EuL2(H(2)O)(3)] were studied by
      means of absorption, and both steady-state and time-resolved luminescence
      spectroscopy. Although L2 displays a very good sensitization efficiency
      (eta(sens.) = 89%), the overall luminescence quantum yield of the complex is
      rather poor (2.6%). This results from strong non-radiative deactivations due to
      the presence of three water molecules in the first coordination sphere, as
      evidenced by luminescence lifetime measurements in H(2)O and D(2)O. The
      relaxation properties of the Gd(3+) complexes obtained with ligands L2 and L1,
      the latter containing an additional pyridine ring in the aromatic core, were
      assessed by means of (17)O NMR and nuclear magnetic relaxation dispersion (NMRD).
      The calculated water exchange rates for both complexes are faster than those of
      currently used contrast agents (k(ex)(298) = 14.0 +/- 1.5 x 10(6) and 11.1 +/-
      1.1 x10(6) s(-1) for [GdL1(H(2)O)(2)] and [GdL2(H(2)O)(3)], respectively). The
      rotational correlation time calculated for [GdL1(H(2)O)(2)] appeared to be long
      (110 +/- 16 ps vs 65 +/- 5ps for [GdL2(H(2)O)(3)]), pointing to a hindered
      rotation due to the larger aromatic frame. Finally, the interaction of the two Gd
      complexes with hydrogencarbonate and phosphate anions was studied by relaxivity
      measurements, showing that both anions are able to compete with water molecules
      as ligands for Gd(3+), with HCO(3)(-) showing a better affinity.

PMID- 19859603
TI  - Substitution reactions between bis-chelate ligands in palladium(II) alkenyl
      complexes: an unusual way to form unstable trans-P complexes. A study on the
      isomerization mechanism.
AB  - The substitution reactions between asymmetric bis-chelate ligands and alkenyl
      chloro derivatives of palladium(II) of the type [Pd(L-L')(Rx)Cl] (L-L' = 2
      phenylsulfanylmethyl-pyridine (HN-SPh), 2-methyl-6-phenylsulfanylmethyl-pyridine
      (MeN-SPh), 2,2'-bipyridinyl (BiPy), Rx = -CCOOMe=CMeCOOMe (Ra), -CCOOEt=CMeCOOEt
      (Rb), -CCOOt-Bu=CMeCOOt-Bu (Rc), -(CCOOMe=CCOOMe)(2)Me (Rd)) with
      phosphoquinoline moieties (8-diphenylphosphanyl-quinoline (DPPQ), 8
      diphenylphosphanyl-2-methyl-quinoline (DPPQ-Me)) usually leads to the formation
      of the stable geometrical isomer bearing these groups in the cis position thanks
      to the mutual trans influence of the alkenyl and phosphine groups. However, when
      the leaving group MeN-SPh and the entering ligand DPPQ are involved, the fast and
      quantitative substitution reaction leads to the formation of a couple of
      geometrical isomers [Pd(DPPQ)(Rx)Cl]-trans P and [Pd(DPPQ)(Rx)Cl]-cis P (Rx = Ra,
      Rb, Rc, Rd) in which the alkenyl and the phosphine groups are in mutual trans or
      cis position. The substrate [Pd(DPPQ)(Rx)Cl]-trans P (Rx = Ra, Rb, Rc) slowly
      interconverts into its thermodynamically stable -cis P counterpart while the
      bulky [Pd(DPPQ)(Rd)Cl]-trans P displays no tendency to isomerize, thereby
      allowing separation of the two geometrical forms. Also, the ligand DPPQ-Me
      induces the formation of the -trans P geometrical isomer which is only detectable
      at low temperature since it rapidly interconverts into the -cis P derivative at
      RT. The kinetics of the interconversion process, a reasonable explanation of the
      observed phenomenon based on theoretical calculations, and eventually an
      unequivocal structure determination of the stable [Pd(DPPQ)(Rx)Cl]-cis P
      substrate are reported in the present paper.

PMID- 19859604
TI  - Mechanistic information from volume profiles for water exchange and complex
      formation reactions of aquated Ni(II). pH, buffer and medium effects.
AB  - Rate and activation parameters for the complex-formation reaction of Ni(2+) with
      4-(2-pyridylazo)-N,N-dimethyl aniline (PADA) were studied as a function of pH in
      different buffers in both aqueous and sodium dodecyl sulfate (SDS) micelle
      solutions. In aqueous Tris buffer solution, the forward and backward rate
      constants increased with increasing pH, while the complex-formation constant
      decreased due to a larger increase in the backward rate constant. The activation
      entropy, DeltaS(#), and activation volume, DeltaV(#), changed with increasing pH
      from positive to negative values, suggesting an apparent changeover from a
      dissociative to a more associative mechanism. Complex-formation reactions with
      2,2'-bipyridine in Tris buffer showed almost no increase in the forward and
      backward rate constants on increasing the pH, but the DeltaS(#) and DeltaV(#)
      values became more negative. N-ethylmorpholine buffer showed no pH effect on the
      rate constants and activation parameters. Water exchange reactions of aquated
      Ni(2+) were also studied as a function of pH under the same conditions. The
      reported rate and activation parameters for water exchange in Tris and N
      ethylmorpholine buffers are consistent with those found for the complex-formation
      reactions of Ni(2+) with PADA. The observed pH and buffer effects for both the
      complex-formation and water exchange reactions of aquated Ni(2+) can be accounted
      for in terms of the formation of a Ni(2+)-Tris complex in Tris buffer and general
      base catalysis by the buffer components. In SDS micelle solution, the complex
      formation reaction with PADA was much faster than in aqueous solution, but the
      increase in rate constant with increasing pH was less significant, while
      DeltaS(#) and DeltaV(#) became more positive, pointing to a more dissociative
      mechanism. For SDS micelle solutions there was no effect on the water exchange
      rate constant or activation volume. Mechanistic interpretations are offered for
      all observed pH, buffer and medium effects.

PMID- 19859605
TI  - Zinc/nickel exchange and ligand cannibalism in N2S2O(1,2) donor ligand sets.
AB  - To explore the displacement of Zn(2+) by Ni(2+) from within N-, S-, and O-chelate
      ligands, (N-(3-thiabutyl)-N'-(3-thiapentaneoate)-1,4-diazacycloheptane)zinc(II),
      Zn-1'-Ac, and 1,4-diazacycloheptane-1,4-diylbis(3-thiapentanoato) zinc(II), Zn-1'
      Ac(2), were reacted with Ni(BF(4))(2) in a methanol solution and were found to
      yield, in both cases, the bright blue, hexa-coordinate Ni-1'-Ac(2) metal
      exchanged product. The latter conditions imply an intact-ligand unwrapping
      process as the hexadentate N(2)S(2)O(2) ligand is transferred from zinc to
      nickel. The former involves transfer of the pentadentate N(2)S(2)O ligand
      generating a green, penta-coordinate nickel intermediate which engages in
      CH(2)CO(2) fragment scavenging from a second zinc unit. This conclusion is
      supported by the observed analogous reformulation of the stable Zn-1'-Ac complex
      into Zn-1'-Ac(2) and the dithiolato [Zn-1'](2) dimer. To our knowledge, this is a
      rare (possibly the first) example of cannibalism reported in such ligand systems.
      The M-1'-Ac(2) complexes were characterized by X-ray diffraction and compared to
      the directly synthesized products.

PMID- 19859606
TI  - pH-dependent assembly of 0D to 3D Keggin-based coordination polymers: structures
      and catalytic properties.
AB  - Four Keggin-based coordination polymers, namely, {[Cu2(4,4'-bpy)(4,4'
      Hbpy)4(H2O)4](SiW12O40)2(H2O)4}n (1), {[Cu2(4,4'-bpy)(4,4'
      Hbpy)6(SiW12O40)3](4,4'-Hbpy)2(H2O)7}n (2), {[Cu2(mu2-H2O)2(4,4'
      bpy)3(SiW12O40)](H2O)6}n (3) and {[Cu2(mu2-OH)(4,4'-bpy)3(SiW12O40)(H2O)]
      [Cu2(mu2-O)(4,4'-bpy)4(H2O)2]0.5 x (H2O)3}n (4) (4,4'-bpy = 4,4'-bipyridine) were
      prepared through the hydrothermal reaction of silicotungstic acid, copper(II)
      nitrate and 4,4'-bipyridine under different pH conditions. Coordination polymers
      1 and 2, which exhibit 0D and 1D structures respectively, were prepared at pH =
      3.5. At pH = 5.5, a 2D coordination polymer 3 was obtained. Increasing the pH of
      the reaction to 8.5 led to a 3D coordination polymer 4. The structural
      diversities of 1-4 reveal that the pH value of the reaction plays a key role in
      the assembly of POM-based coordination polymers. Investigation of the catalytic
      properties of 1-4 for the oxidation of ethylbenzene indicates that the catalytic
      activity of the coordination polymers is closely related to the protonated extent
      of 4,4'-bpy in the coordination polymers.

PMID- 19859607
TI  - Na(I)/Cu(I-II) heterometallic cages interconnected by unusual linear 2-coordinate
      OCN-Cu(I)-NCO links: synthesis, structural, magnetostructural correlation and
      computational studies.
AB  - A new Na(I)/Cu(I-II) heterometallic coordination complex
      [Cu(2)L(2)Na(NCO)(2)Cu](n) (1) with an unusual architecture has been synthesised.
      In 1 cyclic Na-O-Cu-O-Cu cages constructed by the tetradentate N(2)O(2) donor
      Schiff base ligand (H(2)L = N,N'-bis(2-hydroxyacetophenone)propylenediimine) are
      interconnected to each other by a rare singly end-to-end bridged OCN-Cu(I)-NCO
      link generating 1D chain. The complex has been characterised by elemental,
      spectral and structural analysis. The cyclic voltammogram of 1 has been compared
      with the analogous complexes. Cryomagnetic susceptibility studies indicate the
      copper(II) centers in the cyclic Na-O-Cu-O-Cu cages are antiferromagnetically
      coupled with J = -13.8 cm(-1). Complex 1 is a new addition to a class of rare
      singly end-to-end cyanato bridged copper(I) species and interestingly the copper
      ions involved in OCN-Cu(I)-NCO links possess a linear 2-coordinate geometry.
      Density functional theory calculations have been carried out to gain additional
      insights into the metal and ligand orbitals participating in this unusual
      structure.

PMID- 19859608
TI  - Electrical transport properties of In-doped Ce(1-x)In(x)O(2-delta) (x = 0.1;
      0.2).
AB  - We report the synthesis and electrical conductivity of fluorite-type Ce(1
      x)In(x)O(2-delta) (x = 0.1; 0.2) in air, dry Ar, N(2) and H(2) in the temperature
      range of 300-800 degrees C. We have employed a new CO(2) capture technique to
      prepare the "metastable" fluorite-related structure Ce(1-x)In(x)O(2-delta) from
      the corresponding In-doped Ba-containing perovskite of the nominal chemical
      formula BaCe(1-x)In(x)O(3-delta) at 800 degrees C. The amount of CO(2) gained per
      ceramic gram was found to be consistent with the formation of BaCO(3), confirming
      the complete leaching of Ba in BaCe(1-x)In(x)O(3-delta). The CO(2) capture
      efficiency was found to be in the range of 90-99% at 800 degrees C, which is
      significantly higher than those of well-known low-temperature CO(2) absorbing
      materials, including Li(2)O, Li(6)Zr(2)O(7), Li(1.8)Na(0.2)ZrO(3) and LiNaZrO(3).
      Powder X-ray diffraction (PXRD) and energy dispersive X-ray analysis (EDAX)
      confirmed the perovskite into fluorite structural transformation reaction. The AC
      impedance study showed a clear intercept to the real axis at the low-frequency
      over the investigated temperatures in all the atmospheres, indicating a non
      blocking nature of electrode (Pt) and electrolyte interface. The constant phase
      element (CPE) value was found to be in the order of 10(-10) F in air, N(2) and Ar
      for high-frequency part of the semicircle due to bulk contribution, and about two
      orders of magnitude lower values were observed for the low-frequency semicircle
      which may correspond to grain-boundary effect. The 20 mol% In-doped CeO(2)
      exhibits a total electrical conductivity of about 4 x 10(-6) S/cm at 600 degrees
      C in Ar, while in H(2) an about four orders of magnitude higher electrical
      conductivity of 3 x 10(-2) S/cm was observed. The activation energy for
      electrical conductivity was found to be 1.36 eV in Ar, 1.43 eV in N(2), 1.34 eV
      in H(2), and 1.1 eV in air for Ce(0.8)In(0.2)O(1.9).

PMID- 19859609
TI  - Ruthenium alkynyl, carbene and alkenyl complexes containing pendant uracil
      groups: an investigation into the formation of alkenyl-phosphonio complexes.
AB  - The vinylidene complex [Ru(eta(5)-C(5)H(5))(PPh(3))(2)(=C=CHUr)][X] (X = PF(6),
      OTf, Ur = uracil) is a versatile precursor for a range of organometallic
      complexes containing pendant uracil groups. Using appropriate conditions the
      vinylidene complex may be selectively transformed into alkynyl Ru(-C[triple
      bond]CUr)(eta(5)-C(5)H(5))(PPh(3))(2), carbene [Ru(eta(5)
      C(5)H(5))(PPh(3))(2)(=C{OMe}-CH(2)Ur)][X] and alkenyl-phosphonio species [Ru(E
      CH=C{PPh(3)}Ur)(eta(5)-C(5)H(5))(PPh(3))(2)][X]. The synthesis of the related
      alkenyl-phosphonio complexes [Ru(E-CH=C{PPh(3)}R)(eta(5)-C(5)H(5))(PPh(3))(2)][X]
      (R = Ph, C(6)H(4)-3-OMe) is described; these undergo a further orthometallation
      reaction: the mechanism of this latter reaction appears to proceed via
      dissociation of a ruthenium-bound PPh(3) ligand.

PMID- 19859610
TI  - Four mu4-oxo-bridged copper(II) complexes: magnetic properties and catalytic
      applications in liquid phase partial oxidation reactions.
AB  - Four copper(II) complexes, [Cu(4)(O)(L(n))(2)(CH(3)COO)(4)] with N(2)O-donor
      Schiff-base ligands, where HL(1) = 4-methyl-2,6
      bis(cyclohexylmethyliminomethyl)phenol for complex 1, HL(2) = 4-methyl-2,6
      bis(phenylmethyliminomethyl)phenol for complex 2 x CH(3)CN, HL(3) = 4-methyl-2,6
      bis(((3-tri-fluoromethyl)phenyl)methyliminomethyl)phenol for complex 3, HL(4) = 4
      methyl-2,6-bis(((4-tri-fluoromethyl)phenyl)methyliminomethyl)phenol for complex
      4, were synthesized and characterized by elemental analysis, FT-IR, UV-vis
      spectroscopy and finally by single crystal X-ray diffraction study. X-Ray
      analysis reveals that all of these are mu(4)-oxo-bridged tetrameric copper(II)
      complexes. Four copper atoms arrange themselves around an oxygen atom
      tetrahedrally. Magnetic susceptibility measurements show the existence of very
      strong antiferromagnetic coupling among these ions (J = -210.1 to -271.3 cm(-1)),
      mediated by the oxygen atoms. Catalysis of the epoxidation of cyclohexene,
      styrene, alpha-methylstyrene and trans-stilbene by these complexes has been
      carried out homogeneously as well as heterogeneously by immobilizing the metal
      complexes over 2D-hexagonal mesoporous silica. The results obtained in both the
      catalytic conditions show that the olefins are converted to the respective
      epoxides in good yield together with high selectivity.

PMID- 19859611
TI  - Polymer-bound oxidovanadium(IV) and dioxidovanadium(V) complexes: synthesis,
      characterization and catalytic application for the hydroamination of styrene and
      vinyl pyridine.
AB  - The Schiff base (Hfsal-aepy) derived from 3-formylsalicylic acid and 2-(2
      aminoethyl)pyridine has been covalently bonded to chloromethylated polystyrene
      cross-linked with 5% divinylbenzene (PS-Hfsal-aepy). Treatment of
      [V(IV)O(acac)(2)] with PS-Hfsal-aepy in dimethylformamide (DMF) gave the
      oxidovanadium(IV) complex PS-[V(IV)O(fsal-aepy)(acac)] 1, which on oxidation
      yielded the dioxidovanadium(V) PS-[V(V)O(2)(fsal-aepy)] 2 complex. The
      corresponding neat complexes, [V(IV)O(sal-aepy)(acac)] 3 and [V(V)O(2)(sal-aepy)]
      4 have also been prepared. The compounds are characterized in solid state and in
      solution, namely by spectroscopic techniques (IR, UV-Vis, EPR, (1)H, (13)C and
      (51)V NMR), thermal as well as field-emission scanning electron micrograph (FE
      SEM) studies. The crystal and molecular structure of [V(IV)O(sal-aepy)(acac)] was
      solved by single-crystal X-ray diffraction. It is a monomeric complex with the
      tridentate sal-aepy ligand bound equatorially and the two O-atoms of acac(-)
      bound at equatorial and axial positions. These complexes catalyze the
      hydroamination of styrene and vinyl pyridine with amines (aniline and
      diethylamine) yielding a mixture of two hydroaminated products in good yield.
      Amongst the two hydroaminated products, the anti-Markovnikov product is favored
      over the Markovnikov one. Plausible intermediates involved in these catalytic
      processes are established by UV-Vis, EPR and (51)V NMR studies, and an outline of
      the mechanism is proposed. The EPR spectrum of the polymer supported V(IV)O
      complex 1 is characteristic of a magnetically diluted V(IV)O-complex, the
      resolved EPR pattern indicating that the oxidovanadium(IV) centers are well
      dispersed in the polymer matrix. Neat complexes exhibit lower conversion along
      with lower turnover frequency as compared to their polymer-anchored analogues.
      The polymer-anchored heterogeneous catalysts are free from leaching during
      catalytic action and are recyclable.

PMID- 19859612
TI  - Mechanistic aspects of the chemistry of mononuclear Cr(III) complexes with
      pendant-arm macrocyclic ligands and formation of discrete Cr(III)/Fe(II) and
      Cr(III)/Fe(II)/Co(III) cyano-bridged mixed valence compounds.
AB  - The kinetics and mechanism of the redox reaction between [Fe(II)(CN)(6)](4-) and
      the macrocyclic ligand complex [CrClL(15)](2+) (L(15) = 6-methyl-1,4,8,12
      tetraazacyclopentadecane-6-amine) has been studied at different pH values. In
      acidic solution, the expected redox process occurs with no formation of any of
      the possible Cr(III)/Fe(II) mixed valence complexes, as those seen for the
      Co(III) species of the same family, due to the enhanced lability of the Cr(II)
      species formed on Fe(II) to Fe(III) oxidation. In alkaline conditions, the
      formation of the complex [Cr(L(15))(OH)(2)](+) takes place as an initial step
      that precedes a simple substitution process producing the expected cyano-bridged
      Cr(III)/Fe(II) complex. In this species the potentially pentadentate ligand,
      L(15), has a tetradentate coordination mode with a protonated exocyclic primary
      amine group and the redox potential is shifted to more negative values, thus
      disfavouring a redox driven reaction; the equivalent complex
      [CrCl(HL(14))(H(2)O)](3+) (L(14) = 6-methyl-1,4,8,11-tetraazacyclotetradecane-6
      amine) has been prepared by the same method and characterized by X-ray
      crystallography. The final [Fe(II)(CN)(6)](4-) substituted complex,
      [{(HL(15))(OH)Cr(III)NC}Fe(II)(CN)(5)](-) shows pK(a) values of 3.8 and 7.4, as
      expected for the aqua and amino ligands, respectively. Its characterization
      indicated its Class II mixed valence character with a very intense MMCT band at
      350 nm showing a much larger extinction coefficient than that observed for the
      Co(III) complexes of the same family. This fact is in good agreement with the
      much larger Cr(III)-Fe(II) (t(2g)-t(2g)) coupling through cyanide bridging
      ligands expected for these complexes. The fully mixed metal/valence/ligand
      trimetallic complex [{(HL(15))(OH)Cr(III)NC}{L(13)Co(III)NC}Fe(II)(CN)(4)](2+)
      has been prepared following the same procedures and the results are comparable.
      The final complex has the same Class II mixed valence character and its
      electronic spectrum shows the characteristics of both the Fe(II)-to-Cr(III) and
      Fe(II)-to-Co(III) CT bands. The study allows the application of the redox and/or
      substitutionally driven methodology, already described and kinetically designed,
      for the preparation of discrete mixed valence complexes of inert centres, so
      avoiding the unpredictable nature of other approaches seen in the past.

PMID- 19859613
TI  - Influence of metal ions, coligands and reaction conditions on the structural
      versatility and properties of 5-pyrimidyl-tetrazolate containing complexes.
AB  - Eight new complexes containing the versatile multidentate ligand 5-pyrimidyl
      tetrazolate (pmtz), namely [Cu(mu(3)-pmtz)](n) (1), [Pd(2)(mu-pmtz)(2)Cl(2)] (2),
      [Ni(pmtz)(en)(2)]Cl x 2 H(2)O (3), [Cu(tren)(pmtz)(ClO(4))] (4),
      [Co(2)(tren)(2)(mu-pmtz)(mu-O(2))](ClO(4))(3) x 3 H(2)O (5),
      [Fe(2)(pmtz)(4)(H(2)O)(2)(mu-O)] x 5 H(2)O (6), [(UO(2))(4)(mu-pmtz)(2)(mu
      OH)(2)(mu(3)-O)(2)(H(2)O)(4)] x 6 H(2)O (7) and [Dy(2)(pmtz)(4)(mu
      pmtz)(H(2)O)(6)](pmtz) x 6 H(2)O (8), have been prepared by either conventional
      solution or hydrothermal techniques and characterised by single-crystal X-ray
      diffraction. Those compounds prepared under hydrothermal conditions ((1), (2),
      (7) and (8)) exhibit chelating/bridging coordination modes that connect two or
      three metal ions generating polynuclear species. Thus, compound is a 2D polymer
      where the ligand exhibits a new chelating/bridging
      kappa(2)N(1),N(7):kappaN(2):kappaN(3) coordination mode, whereas complexes (2)
      and (7) are dinuclear and tetranuclear species, respectively, in which the ligand
      displays a kappa(2)N(1),N(7):kappaN(2) coordination mode. The increase of the
      metal size favours the adoption of the kappa(2)N(1),N(7):kappa(2)N(4),N(11)
      bis(chelating)bridging mode. This is the case of compound (8) that contains bulky
      Dy(III) metal ions. Despite the large size of the UO(2+) metal ion, the pmtz
      ligand in (7) does not adopt the expected bis(chelating)bridging mode because the
      uranyl cation hydrolyzes to the highly stable bis(mu(3)-oxo) tetranuclear unit.
      Conventional mild solution conditions lead to complexes containing monodentate or
      chelating coordination modes. Thus, compounds (3) and (6) are mononuclear and mu
      oxo dinuclear species, respectively, which contain kappa(2)N(1),N(7) chelating
      pmtz ligands. Compound (4) is mononuclear with the ligand acting in a new
      monodentate form through the N(1) atom of the tetrazolato ring, whereas (5) is a
      dinuclear complex where pmtz adopts a new exo-bidentate N(2),N(3) bridging
      coordination mode. Variable-temperature magnetic measurements of (6) indicate
      that the oxo-bridge mediates a very strong antiferromagnetic interaction between
      the iron(III) ions with a J = -222.7 cm(-1). Luminescence measurements show that
      the pmtz ligands act as "antenna" for energy absorption and transfer to the
      uranyl emissive state.

PMID- 19859614
TI  - Mononuclear iron complexes relevant to nonheme iron oxygenases. Synthesis,
      characterizations and reactivity of Fe-Oxo and Fe-Peroxo intermediates.
AB  - The new ligand L(6)(2)4E (N,N,N',N'-tetrakis(5-ethyl-2-pyridylmethyl)ethane-1,2
      diamine) was designed as a more robust analog of TPEN (N,N,N',N'-tetrakis(2
      pyridylmethyl)ethane-1,2-diamine) for which the ability at stabilizing high
      valent Fe-Oxo and Fe-(hydro)peroxo has been reported. With respect to the latter,
      the pyridyl beta-substituents in L(6)(2)4E do not modify the Fe coordination
      chemistry. From the Fe(II) precursor, [FeO](2+) and Fe(III)-(hydro)peroxo
      intermediates are prepared using the same synthetic methods as those reported for
      the TPEN analogs. The spectroscopic characteristics of all L(6)(2)4E-Fe complexes
      are very similar to their TPEN analog. However, [(L(6)(2)4E)FeO](2+) has a
      greater lifetime than that of [(TPEN)FeO](2+). This can be explained by a
      restricted bimolecular autodegradation due to the bulkiness provided by the ethyl
      substituents. Regarding small organic molecule oxidation, [(L(6)(2)4E)FeO](2+)
      and [(L(6)(2)4E)FeOOH](2+) exhibit behaviours that seem to be general for the
      complexes built with ligands of the TPEN family: [FeO](2+) appears to be
      efficient to epoxidize olefins, whereas [FeOOH](2+) hydroxylates the aromatic
      ring of anisole with efficacy.

PMID- 19859616
TI  - Transition metal-substituted Dawson anions as chemo- and regio-selective oxygen
      transfer catalysts for H2O2 in the epoxidation of allylic alcohols.
AB  - Organic-soluble transition metal-substituted Dawson compounds [(n
      C(4)H(9))(4)N](9)[P(2)W(17)O(61)M(Br)] (M(n+) = Co(2+), Ni(2+), Cu(2+) and
      Zn(2+)), [(n-C(4)H(9))(4)N](7)[HP(2)W(17)O(61)M(Br)] (M(n+) = Cr(3+), Mn(3+) and
      Fe(3+)) and [K/(n-C(4)H(9))(4)N](10-n)[P(2)W(17)O(61)M(H(2)O)] (M(n+) = Ir(4+),
      Ru(3+) and Pd(2+)) have been investigated as oxygen transfer agents for H(2)O(2)
      to a series of primary allylic alcohols to generate epoxides under biphasic
      reaction conditions (1,2-dichloroethane/H(2)O) at 30 or 35 degrees C, such that
      the effect of variations in the substituted transition metals could be evaluated.
      The allylic alcohols involved the species R(1)R(2)C=C(R(3))CH(2)-OH (where R(1),
      R(2) and R(3) = H or Me), as well as cyclic (2-cyclohexen-1-ol), bicyclic [(R-)-(
      )-myrtenol and (R-)-(-)-nopol] and species with two unsaturated sites (geraniol
      and nerol). The reactions are highly chemoselective and regioselective. The order
      of reactivity for the M(II)-substituted species is Pd(II) > Zn(II) > Co(II) >
      Ni(II), and for M(III) and M(IV) substitution is Mn(III) approximately Ir(IV) >
      Fe(III) > Cr(III). The observed orders are consistent with the formation of
      metal(n+)-alcohol species as part of the reaction mechanism. For the more
      polarizing Ir(IV), however, Ir(IV)-alcoholate species are likely involved in the
      mechanism. Formation constants for the Mn(III) and Co(II)-phosphopolyoxotungstate
      alcohol species with all of the above alcohols have been evaluated in 1,2
      dichloroethane at 25 degrees C and range from 19.0-3.5 M(-1). The most likely
      transition state involves coordination of the alcohol to the transition metal
      substituted at the lacunary site, or alkoxide in the case of Ir(IV), along with
      interaction of the double bond of the alcohol with a peroxo group located at a
      W(VI) site adjacent to the substituted transition metal.

PMID- 19859615
TI  - Heteronuclear trimetallic and 1D polymeric 3d-4f Schiff base complexes with OCN-
      and SCN- ligands.
AB  - Reactions of heterobimetallic 3d-4f Schiff base complexes of the formula
      [ZnLnL(H(2)O)(NO(3))(3)] (1a-e) with KOCN or NH(4)SCN in refluxing MeCN produce
      either one dimensional polymeric materials
      [ZnLnL(NO(3))(2)(H(2)O)(OCN)](infinity) (2a-c) or trinuclear complexes of the
      formula [Zn(2)LnL(2)(NO(3))(SCN)(2)] (3a-e) (a (La), b (Nd), c (Er), d (Tb), e
      (Eu); H(2)L = N,N'-bis-(3-methoxysalicylidene)ethylene-1,2-diamine). The
      structures of 2a,b and 3b-e have been determined by single-crystal X-ray
      diffraction studies. Structural differences between the complexes affect the
      photophysical properties, which have been studied in acetonitrile solutions.

PMID- 19859617
TI  - NMR and DFT studies of the complexation of W(VI) and Mo(VI) with 3-phospho-D
      glyceric and 2-phospho-D-glyceric acids.
AB  - Multinuclear ((1)H, (13)C, (17)O, (31)P, (95)Mo, (183)W) magnetic resonance
      spectroscopy (1D and 2D) has been used to study the complexation of molybdate(VI)
      and tungstate(VI) with 3-phospho-D-glyceric and 2-phospho-D-glyceric acids. 3
      Phospho-D-glyceric acid forms four and five complexes, respectively, with
      molybdate and tungstate. These have MO(2)(2+) centres, and involve the
      carboxylate and the adjacent OH groups. Two isomeric 1:2 (metal-ligand) complexes
      are detected, in addition to one mononuclear species having MO(3) centres and
      involving the ligand in a tridentate chelation and a dominant 12:4 species with
      both tungstate(VI) and molybdate(VI). The dominant 12:4 species can be seen as
      two 1:2 complexes bound together in a ring through two diphosphometalate
      moieties, derived from heptamolybdate or heptatungstate, respectively, by
      inclusion of two phosphate groups from the ligands. Tungstate is also able to
      form an additional 2:1 tridentate species. 2-Phospho-D-glyceric acid does not
      interact with tungstate but is able to form one phosphomolybdate species with
      molybdate, which can be regarded as a heptamolybdate derivative. Density
      functional theory (DFT) calculations were performed for 1:2 complexes, including
      calculations on the relative energies of the 1:2 complexes detected in related
      systems, to validate previously proposed structures. The results are compared
      with those obtained from multinuclear NMR spectroscopy.

PMID- 19859618
TI  - Orthogonal non-covalent binding forces in solid state supramolecular herringbone
      shaped "interlocked dimers". Pseudopolymorphism in [(ppy)Pd(mu-pz)](2) (ppy = 2
      (2-pyridyl)phenyl, pz = pyrazol-1-yl) complex.
AB  - The crystal structures of [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz =
      pyrazol-1-yl) (1) and two different solvatomorphs of it, [(ppy)Pd(mu-pz)](2) x
      1/2 CH(2)Cl(2) (2) and [(ppy)Pd(mu-pz)](2) x 1/2 CHCl(3) (3) have been elucidated
      by powder (1 and 2) and single crystal (3) X-ray diffraction. In all of them two
      molecules fit together following a very similar pattern forming a "dimer". All
      neutral dinuclear square-planar complexes having mu-pz or related bridges and
      planar aromatic ligands completing the coordination spheres found in the CSD show
      a similar arrangement to those observed in compounds 1-3, consisting of
      "interlocked dimers" following a herringbone-like pattern. A DFT study reveals
      the simultaneous action of pi,pi- and T-stacking interactions occurring as two
      sets of orthogonally oriented binding forces, as well as anagostic bonds
      overlapped with the latter.

PMID- 19859619
TI  - N1-coordination in palladium(II) and platinum(II) complexes with 9
      methylhypoxanthine: crystal structures and theoretical calculations.
AB  - The synthesis of the new palladium and platinum complexes with 9
      methylhypoxanthine (9-mhypH) of the type [M(dmba)(L)(9-mhypH-N7)]ClO(4) [dmba =
      N,C-chelating 2-(dimethylaminomethyl)phenyl; M = Pd or Pt; L = DMSO, PPh(3) or
      PTA (PTA = 1,3,5-Triaza-7-phosphaadamantane)] is reported. Pd(II) and Pt(II)
      complexes with the anion of 9-mhypH of the type [M(dmba)(L)(9-mhyp-N1)] [L =
      PPh(3) or PTA] have also been prepared. The crystal structures of
      [Pt(dmba)(PPh(3))(9-mhypH-N7)]ClO(4) and [Pt(dmba)(PPh(3))(9-mhyp-N1)] have been
      established by X-ray diffraction. The last complex is the first structurally
      authenticated example of N1 coordination of 9-methylhypoxanthine to platinum. DFT
      based calculations at the BP86/def2TZVP level predict a most favourable
      interaction (both kinetically and thermodynamically) of the metal(II) centre with
      N7 in the neutral ligand 9-mhypH, but with N1 in the deprotonated ligand 9-mhyp(
      ) in agreement with the experimentally observed preference in neutral conditions
      or upon basic treatment, respectively.

PMID- 19859620
TI  - Valence structures of the diastereomeric complexes meso- and rac
      [Ru(2)(acac)(4)(mu-Q)](n) (n = 2-, 1-, 0, 1+, 2+) with the multiple quinonoid
      bridging ligand Q = 1,2,4,5-tetraimino-3,6-diketocyclohexane.
AB  - Meso- and rac-configurated diastereoisomers [Ru(2)(acac)(4)(mu-Q)] have been
      separated and identified as Ru(II)-Q(0) species through a crystal structure
      analysis of the meso form. The presence of two redox-active {Ru(acac)(2)} groups
      (acac(-) = 2,4-pentanedionate) and quinonoid Q with two equivalent pi-conjugated
      alpha-diimine chelate sites and one p-quinone function allowed for the full
      cyclic voltammetric and spectroelectrochemical (UV-vis-NIR, IR, EPR)
      characterisation of the five accessible states (2-, 1-, 0, 1+ and 2+ forms) for
      both isomers. Oxidation occurs at the metal ions to produce Ru(II)Ru(III) mixed
      valent states [Ru(2)(acac)(4)(mu-Q)](+) (K(c) approximately 10(4.5)) with
      corresponding EPR features but without detectable intervalence absorption in the
      near infrared region. IR-spectroelectrochemistry reveals opposite frequency
      shifts for the nu(C=O) and nu(NH) stretching vibrations on reduction and
      oxidation, in agreement with the assumed electronic structure. Reduction leads to
      strongly stabilised [Ru(2)(acac)(4)(mu-Q)](-) states (K(c) approximately 10(11))
      which show weak NIR shoulders around 1040 nm. The EPR characteristics are
      remarkably different for the two isomeric monoanions, reflecting presumably
      flexible geometry and electronic structure. The observation of broad but
      detectable EPR resonance at room temperature in solution and the g factor
      anisotropy in the glassy frozen state at 110 K suggest a rather evenly metal
      ligand mixed singly occupied MO. Together with the ZINDO calculations and the
      partial experimental results reported previously by Masui et al. (Inorg. Chem.,
      2000, 39, 141) for [Ru(2)(bpy)(4)(mu-Q)](n+) (n = 2, 3, 4), the characteristic
      differences provide an insight into the electronic features such as mixed valency
      manifestations and the variable extent of mixing of the metal-quinone frontier
      orbitals of these systems involving Ru(II)-stabilised Q which is unknown as a
      free ligand.

PMID- 19859621
TI  - Heteroditopic ligands based on ferrocenyl benzimidazoles fused to an additional
      diaza heterocyclic ring system.
AB  - The synthesis of ferrocene-based heteroditopic receptors in which the ferrocene
      moiety is attached to an imidazo[4,5-e]benzothiadiazole or imidazo[4,5
      f]quinoxaline is reported. These nitrogen-rich ferrocene derivatives show
      remarkable ion-sensing properties because of the presence of the redox active
      ferrocene unit and the polyazaheteroaromatic ring systems which act as a dual
      binding site for anions and metal cations. They display an anodic shift of the
      oxidation wave (DeltaE(1/2) = 67-200 mV) upon complexation with metal cations and
      a strong cathodic shift (DeltaE(1/2) = -82 to -100 mV) in the presence of F(-)
      and HP(2)O(7)(3-) anions. For the Zn(2+), Cd(2+), Hg(2+) and Pb(2+) metal cations
      tested, the change in the absorption spectra is accompanied by a dramatic colour
      change which allows the potential for "naked eye" detection.

PMID- 19859623
TI  - Prevalence of serotypes and antimicrobial resistance of invasive strains of
      pneumococcus in children: analysis of 9 years.
AB  - OBJECTIVE: To determine the prevalence of serotypes and antimicrobial
      susceptibility of strains of pneumococcus in children and to evaluate the
      implications for vaccine formulation. METHODS: Strains of pneumococcus obtained
      from children admitted with invasive diseases were isolated at Hospital de
      Clinicas of Universidade Federal de Uberlandia, Uberlandia, Brazil, and sent to
      Instituto Adolfo Lutz, Sao Paulo, Brazil, for further identification, serotyping,
      and determination of antimicrobial susceptibility. RESULTS: From April 1999 to
      December 2008, 142 strains of pneumococcus, obtained from children under 5 years
      of age, were analyzed. Seventy-five (52.8%) patients were male, and the age
      ranged from 1 to 60 months (mean age = 19+/-15.4 months; median = 15 months). The
      most common diagnoses were pneumonia [92 cases (64.8%)] and meningitis [33 cases
      (23.2%)]. The strains were mostly isolated from blood [61 samples (43%)], pleural
      fluid [52 samples (36.6%)], and cerebrospinal fluid [28 samples (19.7%)]. The
      most common serotypes were 14, 5, 6B, 1, 6A, 18C, 19A, 3, 9V, 19F, 23F, 9N, and
      10A. There were 14 [9.9%] penicillin-resistant strains, which was detected only
      in the following serotypes: 14, 6B, 19F, 19A, and 23F, being predominant from
      2004 to 2008 (p = 0.000). There was reduced susceptibility to co-trimoxazole
      (79.5%), erythromycin and clindamycin (11.3% each), and ceftriaxone (5.6%).
      CONCLUSIONS: Penicillin resistance was detected in 9.9% of the strains, being
      predominant from 2004 to 2008. Twenty different pneumococcal serotypes were
      identified, and 71.9% of the serotypes were represented in the 7-valent conjugate
      vaccine (PN CRM7) currently available.

PMID- 19859624
TI  - The burden of disease attributable to smoking in Portugal.
AB  - The World Health Organization's (WHO) 2002 Annual Report estimated that about 14%
      of the burden of disease in wealthier countries is attributable to smoking.
      Smoking related diseases include cardiovascular diseases, cancer and respiratory
      diseases. This paper presents an estimate of the burden of disease attributable
      to smoking in Portugal. The estimates are based on the Portuguese demographic and
      health statistics available for 2005. The most important conclusion of the
      analysis is that 11.7% of deaths in Portugal are attributable to smoking. If we
      use disability adjusted life years (DALYs) to measure the burden of disease, we
      find that 11.2% of death DALYs in Portugal is attributable to smoking. The gender
      distribution of this amount is very unequal; 15.4% of the male burden of disease
      and 17.7% of all male deaths can be attributed to smoking, but only 4.9% of the
      female burden of disease and 5.2% of all female deaths. These estimates are
      higher than death estimates previously available (Peto et al. 2006); 14% in men
      and only 0.9% in women. This paper also presents estimates of the burden of
      reducible disease, that is, the reduction in mortality and DALYs that would occur
      if all current smokers quit and thus experienced the mean risk of ex-smokers,
      which is lower than for current smokers but typically not as low as for never
      smokers. Our estimates are that the burden of disease would decrease by 5.8%
      (7.8% in men and 2.8% in women), and that deaths would decrease by 5.8% as well
      (with an 8.5% and 2.9% decrease in men and women, respectively). The paper also
      includes estimates of the burden of disease generated by smoking related
      disability. Smoking related illnesses generated 121,643 DALYs, 72,126 (59%) of
      which are attributable to smoking and 12,417 would be reducible if all smokers
      were to quit.

PMID- 19859625
TI  - Tobacco consumption by the portuguese population. Data from the 2005-2006
      National Health Survey.
AB  - This study aims to contribute to the epidemiological portrayal of tobacco
      consumption in Portugal 2005- 2006, using data from the National Health Survey.
      In this analysis the Portuguese population is characterised according to smoking
      patterns, exposure to smoke and attitudes to smoking in general. Data is
      presented by gender, age groups, regions of residence and other social
      characteristics. Frequencies results are estimated values for the Portuguese
      population in 2005. Logistic binary regression models are used to study regular
      smoking-related characteristics. Results show that 20.9% of the Portuguese
      population (including Madeira and the Azores) aged 15 or more were smokers (male:
      30.9%; female: 11.8%), and that 18.7% smoked regularly. More than one half of men
      were smokers or ex-smokers (56.9%) whereas the great majority of women had never
      smoked (81.3%). After removing the effect of the different age structures among
      regions, the highest rate of males who smoked regularly was observed in the
      Azores region (31.0%), followed by the Alentejo region (29.9%). The highest rate
      of women who smoked regularly occurred in the Lisbon and Tagus Valley region
      (15.4%), followed by the Algarve region (12.8%). Daily average cigarette
      consumption was higher among male (20 cigarettes) than female smokers (13
      cigarettes). The Azores population presented the highest daily average
      consumption (male: 23 cigarettes; female: 16 cigarettes).

PMID- 19859626
TI  - Correlation of clinical findings with functional parameters in elderly asthma
      patients.
AB  - INTRODUCTION: Advanced age is a risk factor for a blunted perception of the
      symptoms, severity and mortality of asthma. There are only a few studies in the
      literature on the relationship between respiratory symptoms and pulmonary
      function in elderly asthmatics. AIMS: To evaluate the divergence between clinical
      and functional classification of asthma in the elderly and to characterise
      subgroups of patients at greater risk of clinico-functional divergence. MATERIAL
      AND METHODS: A cross-sectional study evaluating 41 elderly asthmatics (60 years
      old or over; 33 female; mean age 68.2 years old). Data on age, gender,
      educational level, smoking, time since diagnosis of the disease and weight were
      obtained. Clinical classification, peak expiratory flow measurement and
      spirometry were performed. RESULTS: We found that forced expiratory volume in one
      second (FEV1) correlated positively with the other functional parameters, and
      FEV1 correlated negatively with time since diagnosis of the disease. The
      percentage of clinico-functional divergence was 73.2%. Female patients and those
      with lower levels of schooling had an 8.6 and 9.3 risk of clinico-functional
      divergence respectively. CONCLUSION: The great clinico-functional divergence in
      elderly asthmatics shows the need to establish functional measurements as markers
      of asthma severity.

PMID- 19859627
TI  - Respiratory support strategies for the preterm newborn - National survey 2008.
AB  - BACKGROUND: Respiratory support strategies for the preterm newborn have been the
      subject of intense research. AIM: To survey neonatal respiratory support
      practices in Portugal and to determine whether they reflect evidence from
      randomised trials. METHODS: Questionnaires were given out to 31 Portuguese
      neonatal units to determine the types of ventilators, modes of ventilation, lung
      function monitoring, use of exogenous surfactant, oxygen saturation levels used
      and the prevalence of chronic lung disease in the preterm newborn. RESULTS: There
      was a 94% response rate. Draeger babylog was the most frequently used ventilator
      in neonates. Twelve (41%) units prefer to use early nasal continuous positive
      airway pressure (NCPAP) whenever possible. Triggered ventilation is the choice of
      invasive ventilation in 24 (83%) units (SIMV, SIPPV, PSV); four (14%) units have
      high frequency oscillation ventilation. SIMV is the most frequent (n=13, 45%)
      weaning mode. Exogenous surfactant is used as prophylactic in 12 (41%) units. All
      units use lung function measurements to aid choice of ventilator settings and
      five (17%) units monitor PaCO2 (transcutaneous = 3; capnometry = 2). Seventeen
      (59%) units allow oxygen saturation levels from 90% to 95% in infants with
      respiratory distress syndrome and 15 (52%) levels from 85% to 90% in infants with
      chronic lung disease. Prevalence of chronic lung disease of prematurity ranged
      from 0% to 75% (median: 10). CONCLUSIONS: Many respiratory strategies for
      extremely low birth weight infants reflect the result of large randomised trials.
      More effective methods may be required to encourage the use of early NCPAP
      preferably with binasal prongs, the use of SIPPV as the main weaning mode, the
      use of volume targeted ventilation and a more judicious use of exogenous
      surfactant in order to ensure evidence-based practice.

PMID- 19859628
TI  - Lung and renal transplantation.
AB  - Renal transplantation is the most common type of solid organ transplantation and
      kidney transplant recipients are susceptible to pulmonary complications of
      immunosuppressive therapy, which are a diagnostic and therapeutic challenge. AIM:
      To evaluate patients admitted to the Renal Transplant Unit (RTU) of Hospital de
      S. Joao with respiratory disease. SUBJECT AND METHODS: We performed a
      retrospective study of all patients admitted to RTU with respiratory disease
      during a period of 12 months. RESULTS: Thirty-six patients were included. Mean
      age 55.2 (+/-13.4) years; 61.1% male. Immunosuppressive agents most frequently
      used were prednisolone and mycophenolate mofetil associated with ciclosporin
      (38.9%) or tacrolimus (22.2%) or rapamycin (13.9%). Thirty-one patients (86.1%)
      presented infectious respiratory disease. In this group the main diagnoses were
      23 (74.2%) pneumonias, 5 (16.1%) opportunistic infections, 2 (6.5%)
      tracheobronchitis, and 1 case (3.2%) of lung abscesses. Microbiological agent was
      identified in 7 cases (22.6%). Five patients (13.9%) presented rapamycin-induced
      lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%),
      diagnostic in 10 cases (66.7%). Mean hospital stay was 17.1 (+/-18.5) days and no
      related death was observed. CONCLUSION: Respiratory infections were the main
      complications in these patients. Drug-induced lung disease implies recognition of
      its features and a rigorous monitoring of drug serum levels. A more invasive
      diagnostic approach was determinant in the choice of an early and more specific
      therapy.

PMID- 19859630
TI  - [Tobacco smoking treatment strategy in COPD].
AB  - Smoking cessation is one of the most important ways of improving the prognosis of
      COPD patients. Based on currently available evidence professional health workers
      should take a proactive and continuous role with smokers, motivating them to stop
      smoking and providing treatment to aid smoking cessation. The treatment should
      include pharmacotherapy in addition to behavioural support and should be part of
      management of the patient's chronic respiratory condition, as the COPD National
      Prevention and Treatment Programme recommends. Respiratory physicians and other
      professional health workers should receive training to ensure they have the
      necessary knowledge, attitude and skills to undertake these initiatives or to
      refer the smokers to a suitable qualified specialist. In the near future
      specialised smoking units should provide specific support, promote training,
      improve research and awareness and establish tobacco control measures in
      hospitals and primary health care centres.

PMID- 19859629
TI  - Reclassifying bronchial-pulmonary carcinoma: differentiating histological type in
      biopsies by immunohistochemistry.
AB  - The current state of molecular knowledge on lung cancer demands a histological
      classification which goes beyond small-cell and non-small-cell carcinoma to
      provide support for tailored therapy in aiding in understanding of the drugs
      currently available. As diagnosis and follow-up in the vast majority of lung
      cancer cases is based on biopsies and cytology samples, Immunohistochemical
      Bronchial Pulmonary Carcinoma Classification (IBPCC) is necessary to reveal the
      raft of characteristics available. This provides morphological support for the
      WHO's 1999/2004 classification, in addition to an understanding of
      carcinogenesis. The immunohistochemical panel clarifies the main morphology and
      cytology characteristics to maintain the leading histological types as squamous
      cell carcinoma (high weight molecular cytokeratins/HWMC), adenosquamous carcinoma
      (CK7, TTF1, HWMA), neuroendocrine carcinoma (Chrg, Syn, CD56, TTF1, Ki67),
      adenocarcinoma (CK7, CK20, TTF1) and bring the polymorphic and pleomorphic
      carcinomas under a single banner of pleomorphic carcinoma (Ck7, TTF1, HWMC, VMT,
      Desmin, Actin) which shelters large cell carcinomas and sarcomatoid carcinomas.
      Lung cancer chemotherapy will still be based on platinum and gemcitabine for the
      near future and the IBPCC is a simple and efficient tool for streamlining the
      registration of lung cancer histological characteristics in biopsies and other
      reduced samples to support clinical evidence and trials.

PMID- 19859631
TI  - [Chronic obstructive pulmonary disease - a review].
AB  - COPD is a preventable and treatable disease caused by exposure to tobacco smoke
      and poisonous gases. It is characterised by progressive obstruction of the
      airflow, irreversible once lesions occur in the parenchyma. This article aims to
      systematically review the disease and its treatment. DISCUSSION: Smoking is the
      main cause of COPD and leads to decreased oxygenation via lung hyperinflation
      with reduced airflow as a systemic inflammatory process. This reduces resistance
      to fatigue of the skeletal musculature, leading to hypoxemia, decreased
      peripheral blood flow and also miscarriages and premature births. Inflammatory
      markers such as interleukins and TNF-alpha maintain the systemic picture. While
      smoking cessation improves hypoxemia and exercise intolerance, it does not repair
      damaged tissue. COPD is a serious disease which can be avoided by a wider
      understanding by the population of the harm smoking causes.

PMID- 19859632
TI  - [Pulmonary epithelioid hemangioendothelioma - rarity, diagnosis and treatment
      difficulties].
AB  - The authors report a case of a primary pulmonary epithelioid
      haemangioendothelioma (EHE) in a 51 year-old man, a mechanic, who complained of a
      dry cough followed by constitutional symptoms and dyspnoea. Patient underwent a
      series of diagnostic exams including surgical biopsy and pulmonary tuberculosis
      was diagnosed. He was prescribed tuberculosis drugs for three weeks. Following
      clinical and imagiology deterioration, the case was reviewed by pathologists who
      concluded the pulmonary biopsy revealed an intermediate/high grade pulmonary
      EHE/angiosarcoma. The patient underwent three cycles of chemotherapy with
      carboplatin, etoposide and bevacizumab with no complications. He died seven
      months after onset of symptoms and seven weeks after definitive diagnosis. The
      authors wish to highlight the rarity of this pulmonary neoplasm and the
      importance of clinical suspicion, and the diagnosis and treatment difficulties in
      addition to the potential benefits of antiangiogenic drugs.

PMID- 19859633
TI  - [Pulmonary metastasis in a cardiac angiosarcoma - case report and discussion].
AB  - We present a case report of a 35 year-old male without any relevant former
      pathology admitted to the emergency room with atypical chest pain, cough and
      sputum with ECG changes suggesting pericarditis. He was initially admitted to the
      cardiology ward and experienced clinical improvement after initiating anti-
      inflammatory treatment. As intercurrence he had bacterial origin pneumonia
      complicated by pleural effusion (PE). After discharge patient was referred to a
      pulmonology appointment where aetiological investigation of the PE was
      instigated. Investigation revealed changes in the cardiac cavities and multiple
      lung nodules, suggesting subacute endocarditis with septic pulmonary embolism.
      Admitted to the pulmonology unit patient underwent videothoracsopy which
      diagnosed cardiac angiosarcoma with pulmonary metastisation. Within a few days
      there was a rapid evolution of the clinical picture, with cardiac failure and
      death of the patient without radiotherapy or adjuvant chemotherapy being started.

PMID- 19859634
TI  - [Asthma and its differential diagnoses].
AB  - Allergic bronchopulmonary aspergillosis (ABPA) occurs in immunocompetent patients
      and belongs to the Aspergillus induced hypersensitivity disorders. It is
      estimated that ABPA complicates approximately 7-14% of cases of chronic steroid
      dependent asthma and the same amount of cases of cystic fibrosis. A diagnosis of
      ABPA is based on a combination of clinical, biological and radiology criteria.
      There is a broad spectrum of disease severity. Early detection and aggressively
      management will impede progressive lung damage to a severe and debilitating
      disease requiring lung transplantation. The authors describe the case of a 41
      year-old female with a history of allergic asthma from childhood. It was a
      severe, difficult to control asthma treated with systemic corticosteroids for
      long periods.

PMID- 19859635
TI  - [Testicular tuberculosis: case report].
AB  - Testicular tuberculosis is rare, occurring in approximately 3% of patients with
      genital tuberculosis. It is often clinically indistinguishable from lesions such
      as testicular tumour and infarction and may even mimic testicular torsion. Men
      aged 20-50 years old are most commonly affected and often present with painful or
      painless enlargement of the scrotum. Ultrasound (US) is currently the best
      technique for imaging the scrotum and its contents and for diagnosing testicular
      lesions. We present the case of a 58 year-old male, followed in pneumology for
      pulmonary tuberculosis, who complained of pain and right scrotum enlargement in
      the second month of anti-tuberculosis chemotherapy. First assessment, seconded by
      US, suggested a neoplasic lesion, and the final diagnosis revealed testicular
      tuberculosis.

PMID- 19859636
TI  - [Thoracic nocardiosis].
AB  - Nocardiosis is an opportunistic infection which occurs mostly in
      immunocompromised individuals. Pulmonary presentation is the most frequent;
      however it can affect other parts of the body. Antibiotic treatment is usually
      prolonged to avoid relapses. The authors present a case report of a patient under
      prolonged immunosuppressive therapy for psoriatic arthritis, with complaints of
      right chest pain with one month of evolution.

PMID- 19859637
TI  - [Asthma mimic - a clinical case report].
AB  - Most mediastinal goiters are extensions of cervical goiters. Patients are
      generally female and only occasionally have symptoms. Patients most commonly
      complain of a mass-like sensation, dyspnoea, dysphagia and cough. The authors
      describe the case of a 67 year-old female who presented at the emergency room
      with dyspnoea, anterior cervical discomfort and tightness which had onset a few
      months prior but which had worsened in the last week. The patient cited a history
      of bronchial asthma, for which she was under medication, but the true diagnosis
      was mediastinal goiter.

PMID- 19859638
TI  - Alveolar density measurement and bisphosphonate-related osteonecrosis of the
      jaws.

PMID- 19859640
TI  - Daidzein administration positively affects thyroid C cells and bone structure in
      orchidectomized middle-aged rats.
AB  - SUMMARY: Thyroid C cells hormone, calcitonine, inhibits bone resorption. We have
      demonstrated that daidzein treatment of orchidectomized rats (model for
      osteoporosis) stimulated C cells and increased trabecular bone mass. These
      results suggest that, besides direct action, daidzein may also affect bone
      structure indirectly through enhancement of thyroid C cell activity.
      INTRODUCTION: Thyroid C cells produce calcitonin (CT) which acts as an inhibitor
      of bone resorption. In this study, the influence of daidzein treatment on thyroid
      C cells, bone structure, and bone function in orchidectomized (Orx) middle-aged
      rats was investigated. METHODS: Sixteen-month-old Wistar rats were divided into
      Orx and sham-operated (SO) groups. Half the Orx rats were given subcutaneous
      injections of daidzein (30 mg/kg b.w./day) for 3 weeks. CT-immunopositive thyroid
      C cells were morphometrically analyzed. The metaphyseal region of the proximal
      tibia was measured histomorphometrically, and cancellous bone area (B.Ar),
      trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation
      (Tb.Sp) were calculated. Serum samples were analyzed for CT and osteocalcin (OC),
      calcium (Ca) and phosphorus concentrations, and urine samples for Ca levels.
      RESULTS: Treatment of Orx animals with daidzein significantly increased volume of
      C cells compared to the Orx rats. Daidzein also enhanced B.Ar, Tb.Th, and Tb.N
      and reduced Tb.Sp. The serum OC and urinary Ca concentrations decreased
      significantly in comparison with the Orx group. CONCLUSIONS: These findings
      indicate that daidzein treatment stimulates thyroid C cells, increase trabecular
      bone mass, and decrease bone turnover in Orx middle-aged rats, which is the model
      of male osteoporosis.

PMID- 19859641
TI  - Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and
      pulmonary embolism.
AB  - SUMMARY: Prior studies have associated raloxifene and strontium ranelate with
      deep venous thromboembolism and pulmonary embolism. In a cohort study, we
      observed an increased risk also with the bisphosphonates. However, the increase
      was present already before the start of bisphosphonates pointing at an effect of
      the underlying condition. INTRODUCTION: We seek to study the association between
      use of drugs against osteoporosis and risk of deep venous thromboembolism (DVT)
      and pulmonary embolism (PE). METHODS: Nationwide register-based cohort study from
      Denmark with all users of bisphosphonates and other drugs against osteoporosis
      between 1996 and 2006 (n = 103,562) as cases and three age- and gender-matched
      controls from the general population (n = 310,683). RESULTS: Before start of a
      drug against osteoporosis, an increased risk of DVT/PE was present in the crude
      analysis for alendronate, etidronate, and risedronate. However, upon adjustment,
      this increase in risk disappeared. Before start of raloxifene, a decreased risk
      of DVT/PE was present (odds ratio (OR) = 0.53, 95% confidence interval (CI), 0.39
      0.71). After start of a drug, alendronate (HR = 1.20, 95% CI, 1.00-1.43),
      clodronate (HR = 4.06, 95% CI, 1.47-11.2), and etidronate (HR = 1-37, 95% CI,
      1.23-1.51) were all associated with an increased risk of DVT/PE, while raloxifene
      was only borderline, significantly associated with risk of DVT/PE (HR = 1.64, 95%
      CI, 0.97-2.77). No dose-response relationship was present except for alendronate,
      where the risk was inversely associated with dose, i.e., the risk of DVT/PE
      decreased with increasing average daily dose. The HR for DVT/PE was higher with
      clodronate and etidronate than with alendronate. Alendronate and raloxifene
      carried the same risk for DVT/PE. CONCLUSION: Bisphosphonates seem associated
      with an increased risk of DVT/PE. However, the association does not seem to be
      causal.

PMID- 19859642
TI  - Automated 3D trabecular bone structure analysis of the proximal femur--prediction
      of biomechanical strength by CT and DXA.
AB  - SUMMARY: The standard diagnostic technique for assessing osteoporosis is dual X
      ray absorptiometry (DXA) measuring bone mass parameters. In this study, a
      combination of DXA and trabecular structure parameters (acquired by computed
      tomography [CT]) most accurately predicted the biomechanical strength of the
      proximal femur and allowed for a better prediction than DXA alone. INTRODUCTION:
      An automated 3D segmentation algorithm was applied to determine specific
      structure parameters of the trabecular bone in CT images of the proximal femur.
      This was done to evaluate the ability of these parameters for predicting
      biomechanical femoral bone strength in comparison with bone mineral content (BMC)
      and bone mineral density (BMD) acquired by DXA as standard diagnostic technique.
      METHODS: One hundred eighty-seven proximal femur specimens were harvested from
      formalin-fixed human cadavers. BMC and BMD were determined by DXA. Structure
      parameters of the trabecular bone (i.e., morphometry, fuzzy logic, Minkowski
      functionals, and the scaling index method [SIM]) were computed from CT images.
      Absolute femoral bone strength was assessed with a biomechanical side-impact test
      measuring failure load (FL). Adjusted FL parameters for appraisal of relative
      bone strength were calculated by dividing FL by influencing variables such as
      body height, weight, or femoral head diameter. RESULTS: The best single parameter
      predicting FL and adjusted FL parameters was apparent trabecular separation
      (morphometry) or DXA-derived BMC or BMD with correlations up to r = 0.802. In
      combination with DXA, structure parameters (most notably the SIM and morphometry)
      added in linear regression models significant information in predicting FL and
      all adjusted FL parameters (up to R(adj) = 0.872) and allowed for a significant
      better prediction than DXA alone. CONCLUSION: A combination of bone mass (DXA)
      and structure parameters of the trabecular bone (linear and nonlinear, global and
      local) most accurately predicted absolute and relative femoral bone strength.

PMID- 19859643
TI  - Burden of hip fracture on inpatient care: a before and after population-based
      study.
AB  - SUMMARY: We estimated the excess hospital expenditure attributable to
      osteoporotic hip fracture (HF) within a population of 6,019 patients. Post
      fracture excess of hospital days was 23.1, including 22.7 days in rehabilitation
      care. HF might result from a patient's pre-fracture poor health status rather
      than predispose to a worsening of such pre-existing conditions. INTRODUCTION: Hip
      fracture represents a large burden on hospital services. It is unclear whether
      the post-fracture expenditure is linked to a worsening of pre-fracture comorbid
      conditions. We estimated the excess hospital expenditure attributable to
      osteoporotic HF following the initial hospitalization for acute care (index
      stay). METHODS: We identified 6,019 patients (> or = 50 years) who experienced HF
      in 2005 and compared their hospitalizations 1 year before and 1 year after the
      index stay. Excess expenditure was estimated by subtracting the utilization of
      hospital days or costs (Euros 2005) before the index stay from those after the
      index stay. Factors associated with hospitalization during the pre-fracture and
      post-fracture years were identified using multivariate logistic regressions.
      RESULTS: Beside the index stay, post-fracture excess of hospital days was 23.1
      (95% Confidence Interval (CI) [21.8-24.3]), including 22.7 days (95% CI [21.7
      23.7]) in rehabilitation care and 0.3 days (95% CI [0-0.9]) in acute care.
      Estimated excess cost per patient was <euro>5,986 (95% CI [5,638-6,335]) after
      the index stay, including <euro>5,673 (95% CI [5,419-5,928]) in rehabilitation
      care. Male and elderly patients were at higher risk to be hospitalized in acute
      care during the year preceding and succeeding HF. CONCLUSIONS: Osteoporotic HF
      represents a pronounced excess expenditure in hospital, which is mostly linked to
      rehabilitation care. Considering that utilization of inpatient acute care was
      quite similar before and after the index stay, HF might result from a patient's
      pre-fracture poor health status, rather than predispose to a worsening of such
      pre-existing conditions.

PMID- 19859644
TI  - Does standardized BMD still remove differences between Hologic and GE-Lunar state
      of-the-art DXA systems?
AB  - The standardized bone mineral density (sBMD) values, derived using universal
      standardized equations, were shown to be equivalent within 1.0% for hip but
      significantly different for spine for state-of-art fan-beam dual X-ray
      absorptiometry (DXA) Hologic and GE-Lunar systems. Spine L1-L4 and L2-L4 sBMD
      mean differences between the two systems were 0.042 g/cm(2) (4.1%) and 0.035
      g/cm(2) (3.2%), respectively. INTRODUCTION: The objective of this study is to
      validate the 1994 pencil-beam DXA "universal standardization equations" for state
      of-the-art fan-beam DXA systems. METHODS: The spine and bilateral femurs of 87
      postmenopausal women were scanned on both Hologic Delphi and GE-Lunar Prodigy DXA
      systems at three different clinical centers. The scans were analyzed using
      Hologic Apex and GE-Lunar EnCore software. The BMD results were converted to sBMD
      using the equations previously developed. Linear regression analysis was used to
      describe the relationship of the two systems' BMD results. Bland-Altman analysis
      was used to assess the differences in measures. RESULTS: The Apex and Prodigy
      sBMD values were highly correlated (r ranged from 0.92 to 0.98). Spine L1-L4 and
      L2-L4 sBMD values had significant intercepts and slopes for Bland-Altman
      regression, with mean differences of 0.042 g/cm(2) (4.1%) and 0.035 g/cm(2)
      (3.2%), respectively. The total hip and neck sBMD showed no significant intercept
      and slope, except left total sBMD had a significant difference between the two
      systems of 0.009 g/cm(2) (1.0%). CONCLUSIONS: The sBMD values were shown to be
      equivalent within 1.0% for hip but were significantly different for spine on the
      two systems. Biases may persist in pooled sBMD data from different manufacturers,
      and further study is necessary to determine the cause.

PMID- 19859645
TI  - Successful treatment of sternal fracture nonunion with teriparatide.
AB  - SUMMARY: Fractures have a significant impact on the quality of life for the
      patient in addition to an enormous indirect cost in lost productivity for our
      economy. While majority of fractures heal uneventfully, some fail to heal even
      after many months resulting in nonunion. INTRODUCTION: Sternal nonunions,
      although rare, are particularly onerous for the patient given the magnitude of
      impact on quality of life. METHODS: Current treatment for fracture nonunions
      emphasizes various approaches to surgical fixation in addition to bone grafting.
      These treatments are aggressive and have a variety of drawbacks, rendering them
      suboptimal as a therapeutic approach. CONCLUSION: Based on the success of
      teriparatide in animal studies to accelerate fracture healing, there is growing
      interest in using this drug in humans for the same purpose. We report a case of
      what we believe to be the first successful use of teriparatide in the healing of
      a sternal nonunion fracture.

PMID- 19859646
TI  - Orbital inflammatory disease secondary to a single-dose administration of
      zoledronic acid for treatment of postmenopausal osteoporosis.
AB  - A 60-year-old woman received a single 5-mg dose of zoledronic acid (Aclasta) for
      treatment of postmenopausal osteoporosis. One day after receiving the drug, she
      acutely developed a painful periorbital swelling, chemosis, and hyperemia in the
      right eye. The condition worsened despite initial treatment with topical
      steroids. An orbital CT scan showed right eye proptosis, eyelid edema, and
      intraorbital fat stranding. A diagnosis of orbital inflammatory disease was made,
      and the patient was treated with high-dose oral steroids (prednisone 80 mg/day)
      tapered along 6 weeks. The symptoms and the swelling reduced progressively after
      initiating oral prednisone, and after 12 days, there was complete resolution of
      the condition. The patient remained symptom free and had no remission after the
      treatment interruption.

PMID- 19859647
TI  - PTH improves titanium implant fixation more than pamidronate or renutrition in
      osteopenic rats chronically fed a low protein diet.
AB  - SUMMARY: We evaluated the effects of parathyroid hormone (PTH), pamidronate, or
      renutrition on osseointegration of titanium implants in the proximal tibia of
      rats subject to prolonged low-protein diets. PTH improved mechanical fixation,
      microarchitecture, and increased pull-out strength. Pamidronate or renutrition
      had lesser effects. PTH can thus improve implant osseointegration in protein
      malnourished rats. INTRODUCTION: Protein malnutrition impairs implant
      osseointegration in rats. PTH and pamidronate prevent deleterious effects of
      protein restriction introduced just prior to implantation. Whether these
      treatments improve osseointegration after chronic protein deprivation, i.e., in
      osteopenic bone at time of implantation, is unknown. We evaluated effects of PTH,
      pamidronate, or renutrition on resistance to pull-out of titanium rods implanted
      into the rat tibiae following isocaloric low-protein intake. METHODS: Forty-one
      adult female rats received normal or isocaloric low-protein diets. Six weeks
      later, implants were surgically inserted into proximal tibiae. Following
      implantation, rats on low-protein diets were treated with PTH (1-34),
      pamidronate, saline vehicle, or normal protein diets, for another 8 weeks. Tibiae
      were removed for micro-computerised tomographic morphometry and evaluation of
      pull-out strength. RESULTS: Pull-out strength decreased in rats on isocaloric low
      protein diets compared with normal protein group (-33.4%). PTH increased pull-out
      strength in low-protein group, even compared to controls from the normal protein
      group. PTH and pamidronate increased bone volume/tissue volume, bone-to-implant
      contact, and trabecular thickness, whilst trabecular separation was reduced, with
      a shift to more plate-like bone surrounding the implants. CONCLUSIONS: PTH
      reversed the deleterious effects of long-term protein undernutrition on
      mechanical fixation and bone microarchitecture and improved implant
      osseointegration more than pamidronate or renutrition, likely through changes to
      structure model index.

PMID- 19859650
TI  - [Health care policy in an aging society].

PMID- 19859648
TI  - Patterns of DNA-sequence divergence between Drosophila miranda and D.
      pseudoobscura.
AB  - Contrary to the classical view, a large amount of non-coding DNA seems to be
      selectively constrained in Drosophila and other species. Here, using Drosophila
      miranda BAC sequences and the Drosophila pseudoobscura genome sequence, we
      aligned coding and non-coding sequences between D. pseudoobscura and D. miranda,
      and investigated their patterns of evolution. We found two patterns that have
      previously been observed in comparisons between Drosophila melanogaster and its
      relatives. First, there is a negative correlation between intron divergence and
      intron length, suggesting that longer non-coding sequences may contain more
      regulatory elements than shorter sequences. Our other main finding is a negative
      correlation between the rate of non-synonymous substitutions (d(N)) and codon
      usage bias (F(op)), showing that fast-evolving genes have a lower codon usage
      bias, consistent with strong positive selection interfering with weak selection
      for codon usage.

PMID- 19859649
TI  - [Health inequalities among the aged].
AB  - The aim of this article is to provide an overview of the current state of
      research concerning health inequalities among the aged. First, health
      inequalities are introduced as a general phenomenon. Then, the magnitude of
      inequalities in elderly populations is described for different health indicators.
      In particular, analyses of the association between education and depressive
      symptoms based on a European dataset are presented. Subsequently, different
      hypotheses on age differences in health inequalities and possible explanations
      for social inequalities in health in elderly populations are discussed. Finally,
      some consequences for health policy, which can be derived from current research,
      are outlined.

PMID- 19859651
TI  - Surgical treatment of hilar cholangiocarcinoma in a new era: comparison among
      leading Eastern and Western centers, Leeds.
AB  - OBJECTIVE: Surgery for hilar cholangiocarcinoma (HCCA) remains challenging, with
      radical procedures thought to offer the best chance of long-term survival. Here
      we present our data for surgical resection of HCCA for the period 2001-2008.
      METHODS: A prospectively maintained database was interrogated to identify all
      resections. Clinico-pathological data were analyzed and assessed for impact on
      survival. RESULTS: 51 patients were identified. Almost three-quarters required
      hepatic trisectionectomy. Overall survival was 76% at 1 year, 36% at 3 years and
      20% at 5 years. When R0 resection was achieved, the 5-year survival was 40%.
      Portal vein resection, perineural invasion and T-stage were predictive of overall
      survival on univariate analysis. Only T-stage remained significant on
      multivariate analysis. Lymph node status predicted disease-free survival.
      CONCLUSION: Radical surgery continues to offer the prospect of long-term survival
      for patients with HCCA. Earlier detection and referral to tertiary centers may
      allow more patients to have potentially curative surgical resections.

PMID- 19859652
TI  - Acquired hemophilia A may be associated with itraconazole.

PMID- 19859653
TI  - The expression of astroglial glutamate transporters in patients with focal
      cortical dysplasia: an immunohistochemical study.
AB  - PURPOSE: An abnormal increase in the extracellular glutamate is thought to play a
      crucial role in the initiation, spread, and maintenance of seizure activity.In
      normal conditions, the majority of this excess glutamate is cleared via glial
      glutamate transporters (EAAT-1 and EAAT-2). We aimed to examine the
      immunohistochemical expression of these transporters in the dysplastic tissues of
      patients with focal cortical dysplasia (FCD). METHODS: The parafin-embedded
      dysplastic tissues of 33 patients who were operated on due to medically
      intractable epilepsy and histopathologically diagnosed with FCD between 2001 and
      2006 were stained immunohistochemically with appropriate antibodies, and the
      distribution and intensity of immunoreactivity (IR) of EAAT-1 and EAAT-2 were
      examined.The findings were compared with the histologically normal tissues of
      five patients who underwent temporal lobectomy for epilepsy surgery and 10 fresh
      postmortem cases. RESULTS: In the majority of the patients, the EAAT-1 and EAAT-2
      IR were decreased, their astrocytic expression were lower, and the pattern of
      distribution were more diffused when compared to the control groups.Analyzing
      these findings according to the types of FCD revealed that as the severity of the
      dysplasia increased, the IR and astrocytic expression of both transporters are
      decreased and their distribution tend to be more "diffused." CONCLUSION: The
      results of this study suggest a relationship between the decreased glutamate
      transporter expressions in dysplastic tissues which,in turn, may cause increased
      extracellular concentrations of glutamate and FCD pathophysiology.Further studies
      with larger patient populations,investigating the expression of glutamate
      transporters at mRNA and protein levels, are required to clarify their roles in
      the pathophysiology of FCD.

PMID- 19859654
TI  - Capsules can replace the dura mater after cranial infection.

PMID- 19859655
TI  - Postoperative intracranial seeding of craniopharyngiomas--report of three cases
      and review of the literature.
AB  - PURPOSE: Seeding of craniopharyngioma has been rarely reported. We present three
      cases that ectopically recurred with seeding along the surgical route and CSF
      spaces. METHODS: The first patient was a 13-year-old boy who had initially
      undergone radical excision of a suprasellar and retrosellar craniopharyngioma by
      a right pterional approach. Postoperative MRI showed no evidence of residual
      tumor. Two years later, MRI revealed a local recurrence and in addition a
      separated cystic tumor on the right side adjacent to the middle cerebral artery
      consistent with seeding along the surgical route. Both tumors were removed by re
      operation. On histopathological examination, both, the local recurrent tumor and
      the distant deposit turned out to be adamantinomatous craniopharyngiomas. The
      second patient was a 27-year-old woman who was operated on for the first time via
      a right pterional and 1 year later for a recurrent craniopharyngioma via a
      transsphenoidal approach. Two years later, MRI revealed a right fronto-lateral
      intracranial metastasis at the site of the former craniotomy, which was removed
      by re-craniotomy. This deposit in the operative pathway was found to be an
      adamantinomatous craniopharyngioma, as was the initial tumor. The third patient
      was a 42-year-old man who was operated on 10 years ago for the first time via a
      right fronto-temporal approach. The recent control MRT revealed a right parietal
      intracranial tumor with peripheral contrast enhancement, which was located
      distant to the former craniotomy. The tumor was removed and histopathological
      examination revealed an adamantinomatous craniopharyngioma in accordance with the
      initial tumor. Postoperatively, the three patients were neurologically intact.
      CONCLUSION: Although craniopharyngiomas exhibit a benign histopathological
      pattern, cerebrospinal fluid seeding along the surgical route or along the CSF
      pathways has been observed. Ectopic recurrence of craniopharyngioma suggests that
      meticulous protection of the whole surgical field and careful handling of the
      tumor during the operation are required. It should be emphasized that long-term
      follow-up is mandatory, even in patients undergoing a total removal.

PMID- 19859657
TI  - Comments on Allena et al.: "From drug-induced headache to medication overuse
      headache. A short epidemiological review, with a focus on Latin American
      countries".

PMID- 19859658
TI  - A little bit is not good enough: comprehensive smoking control is needed.

PMID- 19859659
TI  - gamma-radiation-induced gammaH2AX formation occurs preferentially in actively
      transcribing euchromatic loci.
AB  - The central dogma in radiation biology is that nuclear DNA is the critical target
      with respect to radiosensitivity. In accordance with the theoretical
      expectations, and in the absence of a conclusive model, the general consensus in
      the field has been to view chromatin as a homogeneous template for DNA damage and
      repair. This paradigm has been called into question by recent findings indicating
      a disparity in gamma-irradiation-induced gammaH2AX foci formation in euchromatin
      and heterochromatin. Here, we have extended those studies and provide evidence
      that gammaH2AX foci form preferentially in actively transcribing euchromatin
      following gamma-irradiation.

PMID- 19859660
TI  - RNA-seq: from technology to biology.
AB  - Next-generation sequencing technologies are now being exploited not only to
      analyse static genomes, but also dynamic transcriptomes in an approach termed RNA
      seq. Although these powerful and rapidly evolving technologies have only been
      available for a couple of years, they are already making substantial
      contributions to our understanding of genome expression and regulation. Here, we
      briefly describe technical issues accompanying RNA-seq data generation and
      analysis, highlighting differences to array-based approaches. We then review
      recent biological insight gained from applying RNA-seq and related approaches to
      deeply sample transcriptomes in different cell types or physiological conditions.
      These approaches are providing fascinating information about transcriptional and
      post-transcriptional gene regulation, and they are also giving unique insight
      into the richness of transcript structures and processing on a global scale and
      at unprecedented resolution.

PMID- 19859662
TI  - Regulation of HERG (KCNH2) potassium channel surface expression by
      diacylglycerol.
AB  - The HERG (KCNH2) channel is a voltage-sensitive potassium channel mainly
      expressed in cardiac tissue, but has also been identified in other tissues like
      neuronal and smooth muscle tissue, and in various tumours and tumour cell lines.
      The function of HERG has been extensively studied, but it is still not clear what
      mechanisms regulate the surface expression of the channel. In the present report,
      using human embryonic kidney cells stably expressing HERG, we show that
      diacylglycerol potently inhibits the HERG current. This is mediated by a protein
      kinase C-evoked endocytosis of the channel protein, and is dependent on the
      dynein-dynamin complex. The HERG protein was found to be located only in early
      endosomes and not lysosomes. Thus, diacylglycerol is an important lipid
      participating in the regulation of HERG surface expression and function.

PMID- 19859663
TI  - Firefly luciferase: an adenylate-forming enzyme for multicatalytic functions.
AB  - Firefly luciferase is a member of the acyl-adenylate/thioester-forming
      superfamily of enzymes and catalyzes the oxidation of firefly luciferin with
      molecular oxygen to emit light. Knowledge of the luminescence mechanism catalyzed
      by firefly luciferase has been gathered, leading to the discovery of a novel
      catalytic function of luciferase. Recently, we demonstrated that firefly
      luciferase has a catalytic function of fatty acyl-CoA synthesis from fatty acids
      in the presence of ATP, Mg(2+) and coenzyme A. Based on identification of fatty
      acyl-CoA genes in firefly, Drosophila, and non-luminous click beetles, we then
      proposed that the evolutionary origin of firefly luciferase is a fatty acyl-CoA
      synthetase in insects. Further, we succeeded in converting the fatty acyl-CoA
      synthetase of non-luminous insects into functional luciferase showing
      luminescence activity by site-directed mutagenesis.

PMID- 19859661
TI  - Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions
      beyond quality control and the double-life of NMD factors.
AB  - Nonsense-mediated decay is well known by the lucid definition of being a RNA
      surveillance mechanism that ensures the speedy degradation of mRNAs containing
      premature translation termination codons. However, as we review here, NMD is far
      from being a simple quality control mechanism; it also regulates the stability of
      many wild-type transcripts. We summarise the abundance of research that has
      characterised each of the NMD factors and present a unified model for the
      recognition of NMD substrates. The contentious issue of how and where NMD occurs
      is also discussed, particularly with regard to P-bodies and SMG6-driven
      endonucleolytic degradation. In recent years, the discovery of additional
      functions played by several of the NMD factors has further complicated the
      picture. Therefore, we also review the reported roles of UPF1, SMG1 and SMG6 in
      other cellular processes.

PMID- 19859664
TI  - Spermine synthase.
AB  - Spermine is present in many organisms including animals, plants, some fungi, some
      archaea, and some bacteria. It is synthesized by spermine synthase, a highly
      specific aminopropyltransferase. This review describes spermine synthase
      structure, genetics, and function. Structural and biochemical studies reveal that
      human spermine synthase is an obligate dimer. Each monomer contains a C-terminal
      domain where the active site is located, a central linking domain that also forms
      the lid of the catalytic domain, and an N-terminal domain that is structurally
      very similar to S-adenosylmethionine decarboxylase. Gyro mice, which have an X
      chromosomal deletion including the spermine synthase (SMS) gene, lack all
      spermine and have a greatly reduced size, sterility, deafness, neurological
      abnormalities, and a tendency to sudden death. Mutations in the human SMS lead to
      a rise in spermidine and reduction of spermine causing Snyder-Robinson syndrome,
      an X-linked recessive condition characterized by mental retardation, skeletal
      defects, hypotonia, and movement disorders.

PMID- 19859666
TI  - Imaging response criteria for recurrent gliomas treated with bevacizumab: role of
      diffusion weighted imaging as an imaging biomarker.
AB  - The purpose of this study was to assess the usefulness of diffusion weighted
      imaging as an additional imaging biomarker for treatment response in
      recurrent/progressive malignant gliomas treated with bevacizumab alone or in
      combination with other chemotherapeutic agents. Twenty patients treated with
      bevacizumab alone or concurrent chemotherapy were followed up with serial MR
      imaging. Volume and ADC values of contrast enhancing lesion (CEL(vol), CEL(ADC))
      and also of non-enhancing lesion (NEL(vol), NEL(ADC)) were obtained. CEL(vol)
      showed a progressive decrease in non-progressors with a median percentage change
      of -73.2% (P = 0.001) as compared to -33.4% for progressors by 1 year/last
      imaging (P = 0.382). NEL(vol) also showed a decrease in non-progressors on follow
      up imaging though only significant for 3 months follow up (P = 0.042). In
      progressors, CEL(vol) and NEL(vol) showed initial decrease followed by slight
      increase by 1 year/last imaging though not significant (P value of 0.382 and
      0.46, respectively). CEL(ADC) and NEL(ADC) in non-progressors did not show any
      statistically significant change though there was slight trend for positive
      percent change especially for CEL(ADC) by 1 year/last imaging follow up study (P
      value of 0.077 and 0.339, respectively). Progressors showed a progressive
      negative percent change of CEL(ADC) and NEL(ADC). In progressors, NEL(ADC)
      decreased at 6 weeks (P = 0.054), 3 months (P = 0.023) and 1 year/last (P =
      0.078) as compared to baseline study and was also statistically significant as
      compared to non-progressors at 6 weeks (P = 0.047) and 3 months (P = 0.025).
      CEL(ADC) and NEL(ADC) appear to follow different trends over time for non
      progressors and progressors with a stable to slightly progressive increase in non
      progressors and a progressive decrease in progressors, especially early on. These
      findings suggest that DWI may be used as an additional imaging biomarker for
      early treatment response.

PMID- 19859667
TI  - Mutational analysis of the active site residues of a D: -psicose 3-epimerase from
      Agrobacterium tumefaciens.
AB  - D-Psicose 3-epimerase from Agrobacterium tumefacience catalyzes the conversion of
      D: -fructose to D-psicose. According to mutational analysis, the ring at position
      112, the negative charge at position 156, and the positive charge at position 215
      were essential components for enzyme activity and for binding fructose and
      psicose. The surface contact area and distance to the bound substrate by
      molecular modeling suggest that the positive charge of Arg215 was involved in
      stabilization of cis-endiol intermediate. The distances between the catalytic
      residues (Glu150 and Glu244) and Mn(2+) are critical to the catalysis, and the
      negative charges of the metal-binding residues are important for interaction with
      metal ion. The kinetic parameters of the D183E and H209A mutants for metal
      binding residues with substrate and the near-UV circular dichroism spectra
      indicate that the metal ion bound to Asp183 and His209 is involved not only in
      catalysis but also in substrate binding.

PMID- 19859668
TI  - Absence of binding between the human transferrin receptor and the transferrin
      complex of biological toxic trace element, aluminum, because of an incomplete
      open/closed form of the complex.
AB  - Human transferrin (Tf) very tightly binds two ferric ions to deliver iron to
      cells. Fe(III)(2)Tf (Fe(2)Tf) binds to the Tf receptor (TfR) at pH 7.4; however,
      iron-free Tf (apoTf) does not. Iron uptake is facilitated by endocytosis of the
      Fe(2)Tf-TfR complex. Tf can also bind aluminum ions, which cause toxic effects
      and are associated with many diseases. Since Al(III)(2)Tf (Al(2)Tf) does not bind
      to TfR, the uptake of aluminum by the cells does not occur through a TfR-mediated
      pathway. We have studied the absence of binding between Al(2)Tf and TfR by
      investigating the physicochemical characteristics of apoTf, Al(2)Tf, Fe(2)Tf, and
      TfR. The hydrodynamic radius of 38.8 A for Al(2)Tf obtained by dynamic light
      scattering was between that of 42.6 A for apoTf and 37.2 A for Fe(2)Tf. The zeta
      potential of -11.3 mV for Al(2)Tf measured by capillary electrophoresis was close
      to -11.2 mV for apoTf as compared to -11.9 mV for Fe(2)Tf, indicating that the
      Al(2)Tf surface had a relatively scarce negative charge as the apoTf surface had.
      These results demonstrated that the structure of Al(2)Tf was a trade-off between
      the closed and open forms of Fe(2)Tf and apoTf, respectively. Consequently, it is
      suggested that Al(2)Tf cannot form specific ionic interresidual interactions,
      such as those formed by Fe(2)Tf, to bind to TfR, resulting in impossible complex
      formation between Al(2)Tf and TfR.

PMID- 19859669
TI  - [Propranolol therapy to treat problematic hemangiomas : a new standard therapy
      makes its debut].
AB  - Small hemangiomas sometimes produce large findings. Depending on localization,
      local therapy is not always possible. According to a case described in the
      literature, a hemangioma in an infant regressed following cardiologically
      indicated Propranolol. This experience has been used in numerous other cases
      since then and Propranolol has been administered for the indication of a
      hemangioma. Even in cases of very large hemangiomas rapid improvement has been
      observed; successful results persisted even after discontinuation. Particularly
      in cases of problematic localisation, such as in the eye area, prompt therapeutic
      success is important in order to prevent blindness. Relevant studies are in the
      preparatory phase.

PMID- 19859665
TI  - An overview of RNAs with regulatory functions in gram-positive bacteria.
AB  - During the last decade, RNA molecules with regulatory functions on gene
      expression have benefited from a renewed interest. In bacteria, recent high
      throughput computational and experimental approaches have led to the discovery
      that 10-20% of all genes code for RNAs with critical regulatory roles in
      metabolic, physiological and pathogenic processes. The trans-acting RNAs comprise
      the noncoding RNAs, RNAs with a short open reading frame and antisense RNAs. Many
      of these RNAs act through binding to their target mRNAs while others modulate
      protein activity or target DNA. The cis-acting RNAs include regulatory regions of
      mRNAs that can respond to various signals. These RNAs often provide the missing
      link between sensing changing conditions in the environment and fine-tuning the
      subsequent biological responses. Information on their various functions and modes
      of action has been well documented for gram-negative bacteria. Here, we summarize
      the current knowledge of regulatory RNAs in gram-positive bacteria.

PMID- 19859670
TI  - [Distraction and relaxation training in acute tinnitus : effects of a complement
      to otorhinolaryngological treatment].
AB  - BACKGROUND: We examined whether training conceptualized as a complement to
      standard medical treatment (ST) for acute tinnitus to promote patients' capacity
      to distract attention from their tinnitus and to relax (distraction and
      relaxation training) has a positive effect on tinnitus-specific distress
      (tinnitus loudness, tinnitus-related distress and disability), as well as on
      general well-being. PATIENTS AND METHODS: Study participants comprised 29
      patients with tinnitus of maximum 4 weeks' standing (first lifetime tinnitus
      episode) who were randomized to ST (rheological therapy) or advanced standard
      treatment (AST) (rheological therapy complemented by distraction and relaxation
      training). RESULTS: Tinnitus-specific distress was reduced to a significantly
      greater extent in the EST group as compared to ST, especially in patients with a
      striking psychopathology. The improvement in general well-being was comparable in
      both groups. CONCLUSION: In acute tinnitus, distraction and relaxation training
      should be conducted as a complement to standard medical treatment, especially in
      high-risk patients demonstrating abnormal psychopathological status, since
      treatment results can be improved in this way.

PMID- 19859672
TI  - Abstracts of the Irish Thoracic Society Annual Scientific Meeting 2009. Galway,
      Ireland. November 6-7, 2009.

PMID- 19859671
TI  - [Dysphonia following glyphosate exposition].
AB  - Glyphosate is a commonly used nonselective herbicide which inhibits plant growth
      through interference with the production of essential aromatic amino acids.
      Toxicity for humans has been reported after suicidal ingestion. Here we describe
      a 26-year-old teacher who used glyphosate correctly but suffered from severe
      dysphonia after some hours. Laryngostroboscopy revealed decreased vocal fold
      mobility suggesting innervation impairment. The symptoms resolved spontaneously 6
      weeks later and vocal fold mobility returned to normal. Glyphosate neurotoxicity
      has been discussed in the literature therefore, the dysphonia observed here may
      have been due to an intermittent neuropraxia of the laryngeal nerve. However, to
      our knowledge a similar case has not been reported in literature.

PMID- 19859673
TI  - The early history of endoscopic correction of vesicoureteric reflux: the Dublin
      contribution.

PMID- 19859674
TI  - Cell-specific precursor processing.
AB  - The singular gene for a peptide hormone is expressed not only in a specific
      endocrine cell type but also in other endocrine cells as well as in entirely
      different cells such as neurons, adipocytes, myocytes, immune cells, and cells of
      the sex-glands. The cellular expression pattern for each gene varies with
      development, time and species. Endocrine regulation is, however, based on the
      release of a given hormone from an endocrine cell to the general circulation from
      whose cappilaries the hormone reaches the specific target cell elsewhere in the
      body. The widespread expression of hormone genes in different cells and tissues
      therefore requires control of biogenesis and secretion in order to avoid
      interference with the function of a specific hormonal peptide from a particular
      endocrine cell. Several mechanisms are involved in such control, one of them
      being cell-specific processing of prohormones. The following pages present four
      examples of such cell-specific processing and the implications of the phenomenon
      for the use of peptide hormones as markers of diseases. Notably, sick cells - not
      least the neoplastic cells - often process prohormones in a manner different from
      that of the normal endocrine cells.

PMID- 19859675
TI  - Somatostatin and somatostatin receptors.

PMID- 19859676
TI  - Ghrelin: from gene to physiological function.
AB  - The discovery of ghrelin has elucidated the role of the stomach as an important
      organ in the regulation of growth hormone release and energy homeostasis. Ghrelin
      is orexigenic; it is secreted from the stomach and circulates in the blood stream
      under fasting conditions, indicating that it transmits a hunger signal from the
      periphery to the central nervous system. Ghrelin is a peptide hormone, in which
      serine 3 (threonine 3 in frogs) is modified by an n-octanoic acid; this
      modification is essential for ghrelin's activity. Recently the enzymes
      responsible for the processing from the ghrelin precursor to active n-octanoyl
      modified ghrelin have been identified. This review surveys the processing pathway
      from ghrelin gene to mature ghrelin peptide and summarizes our knowledge of the
      regulatory mechanism of ghrelin secretion and function.

PMID- 19859677
TI  - Biosynthesis of cardiac natriuretic peptides.
AB  - Cardiac-derived peptide hormones were identified more than 25 years ago. An
      astonishing amount of clinical studies have established cardiac natriuretic
      peptides and their molecular precursors as useful markers of heart disease. In
      contrast to the clinical applications, the biogenesis of cardiac peptides has
      only been elucidated during the last decade. The cellular synthesis including
      amino acid modifications and proteolytic cleavages has proven considerably more
      complex than initially perceived. Consequently, the elimination phase of the
      peptide products in circulation is not yet well characterized. An ongoing
      characterization of the molecular heterogeneity will help appreciate the
      biosynthetic capacity of the endocrine heart and could introduce new diagnostic
      possibilities. Notably, different biosynthetic products may not be equal markers
      of the same pathophysiological processes. An inefficient post-translational
      prohormone maturation will also affect the biology of the cardiac natriuretic
      peptide system. This review aims at summarizing the myocardial synthesis of
      natriuretic peptides focusing on B-type natriuretic peptide, where new data has
      disclosed cardiac myocytes as highly competent endocrine cells. The structurally
      related atrial natriuretic peptide will be mentioned where appropriate, whereas C
      type natriuretic peptide will not be considered as a cardiac peptide of relevance
      in mammalian physiology.

PMID- 19859678
TI  - VIP and PACAP.
AB  - Vasoactive intestinal polypeptide (VIP) is derived from a 170 amino acid
      precursor which in addition is processed to preproVIP 22-79, PHI, preproVIP 111
      122 and preproVIP 156-170. All preproVIP-derived peptides have been shown in
      normal tissue and VIP-producing cell lines and elevated quantities occur in
      plasma and tumour tissues from patients with VIP-producing tumours. In some
      tissues the dibasic cleavage site after PHI is uncleaved resulting in a C
      terminally extended form, PHV. PHI and VIP are present in a 1:1 molar ratio in
      large dense core vesicles and released in roughly equimolar amounts.
      Carboxyamidation of VIP and PHI is not critical and glycine-extended forms of
      both peptides have been demonstrated. Pituitary adenylate cyclase activating
      polypeptide (PACAP) is derived from a 170 amino acid long precursor, which gives
      rise to PACAP 38, PACAP 27 and PACAP related peptide (PRP). All peptides are
      present in tissue, the dominating form being PACAP 38. Prohormone convertase (PC)
      1 and 2 seem to be involved in the processing of PACAP, except in the testes and
      ovary, where the PACAP precursor is substrate for PC4.

PMID- 19859679
TI  - [Marjolin's ulcer: malignant transformation of a crural ulcer due to
      posttraumatic chronic osteomyelitis].
AB  - We report on the case of an 81-year-old female patient who developed a squamous
      cell carcinoma in a long-lasting therapy-resistant crural ulcer of the lower leg
      due to posttraumatic chronic osteomyelitis. Eventually the lower leg had to be
      amputated because of massive destruction of soft tissue and the tibia bone. Based
      on the desolate wound conditions plastic reconstruction by a pivoted muscle flap
      and surgical covering with mesh graft plastic was also necessary.The amputation
      stump had completely healed 6 months after surgery and the patient is fitted with
      an artificial limb ensuring independent mobility even outside the home. Up to the
      present there is no evidence of any tumor recurrence or progression.

PMID- 19859680
TI  - [Thrombosis prophylaxis in trauma surgery units in Germany: a survey].
AB  - BACKGROUND: A questionnaire study was conducted to ask trauma surgery centers
      about thrombosis prophylaxis methods and strategies for the diagnosis and therapy
      of heparin-induced thrombocytopenia (HIT). METHODS: Questionnaires were sent by
      post to German hospitals with trauma surgery units inquiring about the use of
      unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH), the
      duration of medication, and the HIT diagnosis. Questionnaires were evaluated
      descriptively. RESULTS: 314 of 685 questionnaires sent out were evaluable (46%):
      half were from general hospitals, 96 (31%) from specialized hospitals, and 53
      (17%) from tertiary care hospitals (others: 8). In more than 90%, only LMWH was
      used. The mean duration of pharmacological thrombosis prophylaxis was 16.6+/-10.4
      days (inpatient/outpatient). Only 10% adhered to the recommended platelet count
      controls every 2 days (days 5-14) for early detection of HIT. CONCLUSIONS: While
      pharmacological thrombosis prophylaxis following trauma surgery seems to be
      generally performed according to guidelines, diagnosis and treatment of HIT need
      to be systematized.

PMID- 19859681
TI  - [Conclusion: How should a meaningful meta-analysis of long-term psychodynamic
      psychotherapy be designed?].
AB  - In their answer to our critical evaluation of their meta-analysis about long-term
      psychodynamic psychotherapy (LTPP), Leichsenring and Rabung claim that all our
      critical points could be rejected. This is surprising, as the authors already
      confirmed different shortcomings of their analysis. Our major criticism is that
      the meta-analysis is based on very few high-quality studies (including follow-up
      assessments), but on many studies with poor quality and/or observational studies
      resulting in serious publication bias. Neither the treatment of interest (LTPP)
      nor the target group is sufficiently circumscribed, but the very few studies are
      misinterpreted as if confirming efficacy of all psychodynamic interventions for
      nearly all psychiatric groups. Superior efficacy over other effective
      psychological interventions is mentioned, although not justified by data. Patient
      selection bias which is a major issue in long-term treatments is not addressed
      adequately and led to erroneous conclusions that the more treatment people
      receive, the higher the benefit. To conclude, the authors try to suggest far
      reaching conclusions which are only based on a few studies with poor data
      quality.

PMID- 19859682
TI  - ["Psychoanalysis should be rescued. By all means?"].

PMID- 19859683
TI  - [A favourite adversary: "classic long-term psychoanalysis". Commentary on Rief
      and Hofmann's "Psychoanalysis should be rescued. By all means?"].
AB  - Rief and Hofmann (2009, Nervenarzt 80:593-597) harshly criticise the meta
      analysis on the effectiveness of long-term psychodynamic psychotherapy (LTPP) by
      Leichsenring and Rabung (2008, JAMA 300(13):1551-1565). They find fault with the
      inclusion of naturalistic studies in addition to randomised clinical trials.
      Furthermore, they criticise the heterogeneity of the treatments included and the
      disorders studied. They suspect that a number of RCTs of LTPP with negative
      results for LTPP have been done and not been published. This paper comments on
      the following issues: the strict determination of RCTs is scientifically outdated
      and in order to investigate the effectiveness of psychotherapy naturalistic
      studies have to be included; the heterogeneity of studies included in meta
      analysis as well as the heterogeneity of the patients studied reflect clinical
      reality, which is the purpose of effectiveness studies. The accusation of
      repressing results of LTPP RCTs is unsustainable. All in all, the meta-analysis
      by Leichsenring and Rabung was done accurately, and the results were controlled
      for by separate analyses of single subgroups. Therefore, their study does provide
      evidence of the effectiveness of long-term psychodynamic psychotherapy for
      patients with complex mental disorders.

PMID- 19859684
TI  - [Core symptoms of depression].

PMID- 19859686
TI  - [Current developments in vascular ultrasound].
AB  - Ultrasound plays a central role in the diagnostic imaging of venous and arterial
      vessels, especially for the assessment or exclusion of arteriosclerotic vessel
      obstructions as well as venous or arterial thrombosis. Due to its excellent
      patient acceptance and its broad availability, ultrasound is considered the
      standard method of choice for vascular imaging. New techniques and methods have
      greatly enhanced its diagnostic accuracy, the most notable of which are the B
      flow technique, a variant of Doppler signal read-out for reduction of artifacts
      in duplex sonography, as well as other techniques, such as tissue harmonic
      imaging, the cross-beam technique and the speckle-reduction technique, which
      employ different echo processing methods for contrast improvement and enhanced
      delineation of body structures adjacent to the vessels. The introduction of
      contrast enhanced ultrasound represents an important advancement and has brought
      a substantial improvement in sensitivity. This article describes and discusses
      these new techniques and methods of vascular ultrasound diagnostics with respect
      to their diagnostic value.

PMID- 19859685
TI  - [Personality in old age].
AB  - Modern developmental psychology tends to draw a positive, resource-based picture
      of human aging. We will however focus on more difficult aspects of personality in
      old age which are of psychiatric relevance: the persistence of cluster A and C
      personality disorders, antisocial personality in the elderly; the interaction of
      personality and a detection of mild cognitive impairment (MCI); personality
      features as risk or protective factors or early signs of Alzheimer's dementia;
      changes of personality in Parkinson's disease and frontotemporal dementia. We
      will briefly mention recent neuroimaging studies which appear to suggest a
      functional neuroanatomy of personality. A quote from Cicero's cato major, de
      senectute indicates that some of his perceptions regarding classic personality
      characteristics of the elderly can be recognized in our patients and can be
      prevented or treated with modern interventions.

PMID- 19859687
TI  - [Ultrasound investigation of vessels supplying the extremities].
AB  - Ultrasound investigation of the vascular supply to legs and arms has become a
      standard procedure and is performed in all kinds of both arterial occlusive
      disease and venous disease. On the arterial side the most common disease is
      atherosclerosis in which stenoses and occlusions can be identified and
      characterized with respect to the functional significance. Sensitivity und
      specificity for the detection of symptomatic occlusions and stenoses are
      approximately 90% and 99%, respectively. This is the basis for planning invasive
      procedures, catheter interventions as well as operations. The short term success
      can be assessed and long term follow-up can be performed by ultrasound. In
      addition all other kinds of arterial disease (embolisms, aneurysms, inflammation
      and mechanical alterations) can be examined. On the venous side, the most common
      indication for ultrasound is the suspicion of deep vein thrombosis. Compression
      ultrasound of the leg veins allows a reliable diagnosis in almost all cases. The
      diagnostic failure rate in a 3-month follow up is around 0.5%. The present review
      summarizes the indications and examination details for leg arteries, arm
      arteries, leg veins and arm veins. A separate paragraph deals with dialysis
      shunts, a growing field in vascular medicine.

PMID- 19859688
TI  - [Second-line therapy of idiopathic detrusor overactivity. Sacral neuromodulation
      and botulinum toxin A].
AB  - The syndrome of idiopathic overactive bladder (I-OAB) impairs quality of life for
      the affected individuals. Conservative treatment options such as antimuscarinics
      are not always effective, and resulting side effects can lead the patient to stop
      treatment. In recently years, minimally invasive and reversible sacral
      neuromodulation and botulinum toxin A have become available. Currently, the
      approved treatment option for I-OAB that is recommended by the International
      Consultation on Incontinence is sacral neuromodulation by InterStim therapy. This
      article gives an overview of the present clinical evidence on the effectiveness
      and reliability of these two treatment modalities as well as the current
      significance of sacral neuromodulation and botulinum toxin A for the second-line
      treatment of adult I-OAB.

PMID- 19859689
TI  - [Seminoma necrosis by testicular torsion].
AB  - The coincidence of a classical scrotal testicular torsion with a scrotal tumor is
      a rare event. In the case described here the classical histological
      characteristics of a seminoma were present in addition to clear signs of
      testicular torsion with fibrin-containing thrombi in the intratesticular
      capillaries, so that the ischemia time predicted by the pathologists correlated
      well with the clinical data of 7.5 h for the testicular torsion estimated at the
      time of the intervention. The intraoperative diagnosis made by the surgeon
      allowed a rapid response with only a semi-castration, excision of the wound edges
      and a highest possible amputation of the funiculus.

PMID- 19859690
TI  - [Fistula between the bladder and vagina and perforation after implantation of a
      wall stent for ureteral stricture].
AB  - The implantation of metal stents in the ureter is an alternative therapeutic
      option for treating ureteral strictures of different origins. We report the case
      of a female patient who was treated with a ureteral wall stent because of
      stenosis caused by radiotherapy. Subsequently the stent migrated into the bladder
      and led to incrustation and stone formation. This finally led to development of a
      vesicovaginal fistula and bladder perforation into the os pubis.

PMID- 19859691
TI  - Diabetes treatment with insulin glargine and risk of malignancy: methodological
      pitfalls and ethical issues.

PMID- 19859692
TI  - Ligament releases do not lead to increased postoperative varus-valgus laxity in
      flexion and extension: a prospective clinical study in 49 TKR patients.
AB  - This prospective study investigated whether ligament releases necessary during
      total knee replacement (TKR) led to a higher varus-valgus laxity during
      intraoperative examination after implantation of the prosthesis and after 6
      months. The laxity values of TKR patients were also compared to healthy controls.
      Varus-valgus laxity was assessed intra- and postoperatively in extension and 70
      degrees flexion in 49 patients undergoing TKR, implanted using a balanced gap
      technique. Knees were catalogued according to ligament releases performed during
      surgery. Postoperative varus-valgus laxity and laxity after 6 months had not
      increased following release of the posteromedial capsule, iliotibial tract, and
      the superficial medial collateral ligament. The obtained postoperative laxity
      compares well with a healthy equally aged control group. It can be concluded that
      the balanced gap technique results in stable knees and that releases can safely
      be performed to achieve neutral leg alignment without causing postoperative
      laxity.

PMID- 19859693
TI  - Effect of dihydrotestosterone on cultured human tenocytes from intact
      supraspinatus tendon.
AB  - The role of hormones in the pathogenesis of tendinopathy is not well recognised,
      even though the use of anabolic steroids is correlated with a higher incidence of
      spontaneous tendon ruptures. The aim of this study was to investigate the effects
      of dihydrotestosterone (DHT) on human tenocyte cultures from the intact
      supraspinatus tendon of male subjects. Cultured human tenocytes were seeded into
      culture plates at a density of 5 x 10(4) cells per well and incubated for 24 h.
      Then, 10(-9) M-10(-7) M DHT or Dulbecco's modified Eagle's medium (DMEM) only
      (control) was added to the culture plate wells. Cell morphology assessment and
      cell proliferation tests were performed 48, 72 and 96 h after DHT treatment. DHT
      treated tenocytes showed an increased proliferation rate at DHT concentration
      higher than 10(-8) M. Differences in cell numbers between control and DHT-treated
      cells were statistically significant (P < 0.05) after 48 and 72 h of treatment
      with DHT concentrations of 10(-8) and 10(-7) M. The tenocytes treated with DHT
      (10(-8) and 10(-7) M) became more flattened and polygonal compared to control
      cells that maintained their fibroblast-like appearance during the experiment at
      each observation time. In conclusion, in vitro, progressive increasing
      concentration of DHT at doses greater than 10(-8) M had direct effects on male
      human tenocytes, increasing cell number after 48 and 72 h of treatment, and
      leading to a dedifferentiated phenotype after 48 h of treatment. This effect can
      be important during tendon-healing and repair, when active proliferation is
      required. Our results represent preliminary evidence for a possible correlation
      between testosterone abuse and shoulder tendinopathy.

PMID- 19859694
TI  - Arthroscopic technique for fragment fixation using absorbable pins for
      osteochondritis dissecans of the humeral capitellum: a report of 4 cases.
AB  - This is the first report to describe a method of arthroscopic osteochondral
      fixation using absorbable pins to treat osteochondritis dissecans (OCD) of the
      capitellum. Four adolescent baseball players with OCD of the capitellum were
      treated, and good short-term results were obtained. During this arthroscopic
      procedure, the elbow was maintained in the maximum flexed position, and
      posterolateral portals were used to visualize the lesion, perform drilling, and
      insert the pins. This procedure is less invasive and easier to perform than other
      fixation procedures that require harvesting or production of autologous bone
      pegs. This is an effective method of fragment fixation with absorbable pins.

PMID- 19859695
TI  - Treatment of osteochondral lesions of the talus: a systematic review.
AB  - The aim of this study was to summarize all eligible studies to compare the
      effectiveness of treatment strategies for osteochondral defects (OCD) of the
      talus. Electronic databases from January 1966 to December 2006 were
      systematically screened. The proportion of the patient population treated
      successfully was noted, and percentages were calculated. For each treatment
      strategy, study size weighted success rates were calculated. Fifty-two studies
      described the results of 65 treatment groups of treatment strategies for OCD of
      the talus. One randomized clinical trial was identified. Seven studies described
      the results of non-operative treatment, 4 of excision, 13 of excision and
      curettage, 18 of excision, curettage and bone marrow stimulation (BMS), 4 of an
      autogenous bone graft, 2 of transmalleolar drilling (TMD), 9 of osteochondral
      transplantation (OATS), 4 of autologous chondrocyte implantation (ACI), 3 of
      retrograde drilling and 1 of fixation. OATS, BMS and ACI scored success rates of
      87, 85 and 76%, respectively. Retrograde drilling and fixation scored 88 and 89%,
      respectively. Together with the newer techniques OATS and ACI, BMS was identified
      as an effective treatment strategy for OCD of the talus. Because of the
      relatively high cost of ACI and the knee morbidity seen in OATS, we conclude that
      BMS is the treatment of choice for primary osteochondral talar lesions. However,
      due to great diversity in the articles and variability in treatment results, no
      definitive conclusions can be drawn. Further sufficiently powered, randomized
      clinical trials with uniform methodology and validated outcome measures should be
      initiated to compare the outcome of surgical strategies for OCD of the talus.

PMID- 19859696
TI  - Sartorial branch of the saphenous nerve in relation to a medial knee ligament
      repair or reconstruction.
AB  - Surgical approaches to repair or reconstruct the medial knee structures note
      caution to avoid the sartorial branch of saphenous nerve. However, the
      approximate area of potential iatrogenic nerve injury has not been previously
      described in relation to landmarks for a medial knee reconstruction. The purpose
      of this study was to define the course of the sartorial branch of the saphenous
      nerve in relation to the superficial medial collateral ligament. A total of ten
      non-paired, fresh-frozen cadaveric knees, with no evidence of prior injury or
      disease were utilized. Dissection to identify the medial knee structures was
      performed. The sartorial branch of the saphenous nerve was identified in all
      specimens. The perpendicular distance from the anterior border of the superficial
      medial collateral ligament 2 cm distal from the joint line to the sartorial
      branch of the saphenous nerve was 4.8 +/- 0.9 cm. The distance from the anterior
      border of the superficial medial collateral ligament to the sartorial branch of
      the saphenous nerve decreased as the distance was increased distally with a mean
      distance of 4 cm (4.1 +/- 0.8 cm) distal from the joint line and 6 cm (3.8 +/-
      0.8 cm) distal from the joint line. We have characterized the surgically relevant
      landmark anatomy of the sartorial branch of the saphenous nerve in regards to
      performing a repair or reconstruction of the medial knee structures. Familiarity
      with these anatomic landmarks and associated distances from the sartorial branch
      of the saphenous nerve, we can assess the potential area of vulnerability to this
      nerve branch intraoperatively.

PMID- 19859697
TI  - Attenuation of cocaine-induced reinstatement of drug seeking in squirrel monkeys:
      kappa opioid and serotonergic mechanisms.
AB  - RATIONALE: Kappa agonists can attenuate reinstatement of cocaine-seeking behavior
      induced by cocaine priming. The mechanisms underlying this effect have not been
      characterized fully but may have a serotonergic component as kappa agonists also
      increase the release of serotonin (5-hydroxytryptamine, 5-HT). OBJECTIVES: This
      study investigated the role of kappa opioid receptor and 5-HT mechanisms in kappa
      agonist-induced attenuation of cocaine priming in monkeys. METHODS: Squirrel
      monkeys were trained to self-administer cocaine (0.18-0.3 mg/kg/injection) under
      a second-order schedule in which drug seeking was maintained jointly by cocaine
      injections and a cocaine-paired visual stimulus. In extinction sessions, saline
      was substituted for cocaine, and the cocaine-paired stimulus was omitted. During
      test sessions, only saline was available for self-administration, and response
      contingent presentations of the cocaine-paired stimulus were restored. RESULTS:
      Priming injections of cocaine (0.1-1.0 mg/kg) induced reinstatement of drug
      seeking. Maximal levels of responding were similar to those maintained by active
      cocaine self-administration. Pretreatment with the kappa agonists enadoline (0.01
      mg/kg) and spiradoline (0.3 mg/kg) or the 5-HT transport inhibitors fluoxetine
      (5.6 mg/kg) and citalopram (10.0 mg/kg) attenuated the priming effects of
      cocaine, shifting the cocaine dose-response function rightward and downward.
      Inhibition of cocaine-induced reinstatement of drug seeking by spiradoline and
      fluoxetine was reversed by R(+)8-hydroxy-2-(di-n-propylamino)tetralin (0.03
      mg/kg), a 5HT(1A) agonist that inhibits 5-HT release. The effects of spiradoline
      also were reversed by the kappa antagonist nor-binaltorphimine (10.0 mg/kg).
      CONCLUSIONS: Results suggest that the capacity of kappa opioid agonists to
      increase extracellular 5-HT levels may at least partially underlie kappa agonist
      induced modulation of cocaine seeking.

PMID- 19859698
TI  - Evaluation of potential sex differences in the subjective and analgesic effects
      of morphine in normal, healthy volunteers.
AB  - RATIONALE: Sex differences in the analgesic effects of mu-opioid agonists have
      been documented extensively in rodents and, to a lesser extent, in non-human
      primates. To date, there have been few experimental studies investigating this
      effect in humans, and the conclusions have been equivocal. OBJECTIVES: The aims
      of the present study were to examine potential sex differences in the analgesic,
      subjective, performance, and physiological effects of morphine in human research
      volunteers. METHODS: Using a double-blind outpatient procedure, the present study
      investigated the effects of intramuscular morphine (0, 5, and 10 mg/70 kg, i.m.)
      in men (N = 8) and women (N = 10). The primary dependent measure was analgesia,
      as assessed by the cold pressor and mechanical pressure tests. Secondary
      dependent measures included subjective, performance, and physiological effects of
      morphine, as well as plasma levels of morphine. RESULTS: No differences in the
      analgesic and performance effects of morphine were observed between men and
      women, but significant differences in morphine's subjective effects were found.
      Specifically, men reported greater positive effects, whereas women reported
      greater negative effects after morphine administration. CONCLUSIONS: These data
      suggest that, in humans, there are sex differences in the subjective mood
      altering effects of morphine but, based on this limited sample, there is little
      evidence for sex differences in its analgesic effects.

PMID- 19859699
TI  - A randomised trial of glucose tablets to aid smoking cessation.
AB  - RATIONALE: Oral glucose has been found to decrease tobacco craving among
      abstaining smokers. One study has demonstrated an effect of glucose on short-term
      abstinence. There is a need to examine any long-term benefit of glucose on
      abstinence. OBJECTIVES: To assess whether glucose tablets improve 6-month
      continuous abstinence rates compared with low-calorie placebo tablets. METHODS:
      Smokers attempting to stop (n = 928) were randomised to receive glucose or
      sorbitol (placebo) in a double-blind placebo-controlled trial. All participants
      received group-based psychological support, and approximately half (n = 474)
      received nicotine replacement therapy (NRT), buproprion, or both. Smokers were
      seen weekly for 5 weeks and used tablets ad libitum, with a recommended minimum
      of 12 per day. Participants were recruited through general practitioner referral,
      word of mouth, and advertising. The participants were 38% male, smoked an average
      of 23.5 cigarettes per day, and had a mean age of 44 years. There were no
      significant pretreatment differences between groups. The primary outcome measure
      was continuous, CO-verified abstinence from the target quit date for 6 months.
      RESULTS: No significant effect of glucose tablets on abstinence was found (14.6%
      vs 13.4% abstinence in the glucose and placebo groups, respectively). However,
      there was a significant interaction with a glucose effect observed in smokers
      also receiving other medication (18.2% vs 12.6%, p < 0.05) but not otherwise
      (10.7% vs 14.3% ; p < 0.05 for the interaction). CONCLUSIONS: No significant
      effect of glucose tablets over and above sweet tasting tablets could be detected
      overall, but the possibility of an effect as an adjunct to NRT or bupropion
      merits further investigation.

PMID- 19859700
TI  - Electrochemical deposition of silicate-cetyltrimethylammonium bromide
      nanocomposite film on glassy carbon electrode for sensing of methyl parathion.
AB  - A novel electrochemical sensor for methyl parathion based on silicate-
      cetyltrimethylammonium bromide nanocomposite film has been fabricated by electro
      assisted deposition onto glassy carbon electrode in one-step via an
      electrochemical modulation of pH at the electrode/solution interface to promote
      controlled gelification of tetraethylorthosilicate sol, and was characterized
      with scanning electron microscopy, X-ray diffraction, and electrochemical
      impedance spectroscopy. The electrochemical sensing of methyl parathion on the
      film-modified electrode was investigated applying cyclic voltammetry and square
      wave voltammetry. Compared to the unmodified electrode, the shapes of the redox
      peaks were improved and the peak currents significantly increased. Experimental
      parameters such as deposition time, pH value, and accumulation conditions have
      been optimized. A linear relationship between the peak current and methyl
      parathion concentration was obtained in the range from 1.0 x 10(-7) to 1.0 x 10(
      4) mol L(-1) with a detection limit of 1.04 x 10 (-8) mol L(-1) (S/N = 3) after
      accumulation at 0 V for 120 s. The film electrode shows great promise for
      determination of methyl parathion in real samples.

PMID- 19859701
TI  - The regional distribution of T2-relaxation times in MR images of the substantia
      nigra and crus cerebri.
AB  - INTRODUCTION: When scanning the size of the substantia nigra (SN), for example in
      Parkinson's disease, it is important to precisely locate its true anatomic
      location. The hypointense areas on T2-weighted magnetic resonance images (T2w) at
      the level of the upper midbrain are usually labeled as the SN. Recent studies
      showed that the line of demarcation between the SN and the crus cerebri (CC) in
      T2w images seems not to be clear. The purpose of our study was to evaluate the
      depiction of the SN and the CC on calculated R2 maps by analyzing the regional
      distribution of T2 values in both regions. METHODS: In 36 healthy subjects,
      triple echo turbo spin echo were obtained at 1.5 T and R2 maps calculated. Proton
      density-weighted turbo spin echo images (PDw) were used as reference. The CC and
      SN were manually traced on PDw sections (CCP and SNP) and also the hyperintense
      areas on the R2 maps, suggestive of the SN (DT2). The obtained volumes were
      evaluated in terms of total size, intersections size, and residual areas, as well
      as the corresponding T2 values. RESULTS: DT2 corresponded to anterolateral parts
      of the SNP and showed an extension to anteromedial part of the CC. The
      intersections between DT2 and CCP and DT2 and SNP presented both decreased but
      different T2 values (102 +/- 5 and 95 +/- 4 ms). CONCLUSION: An exact
      differentiation of the SN from the CC is not possible on the basis of T2w images
      but rather on the basis of the underlying calculated T2 values from the triple
      echo sequence.

PMID- 19859702
TI  - C-arm flat detector computed tomography: the technique and its applications in
      interventional neuro-radiology.
AB  - INTRODUCTION: Flat detector computed tomography (FDCT) is an imaging tool that
      generates three-dimensional (3-D) volumes from data obtained during C-arm
      rotation using CT-like reconstruction algorithms. The technique is relatively new
      and, at current levels of performance, lags behind conventional CT in terms of
      image quality. However, the advantage of its availability in the interventional
      room has prompted neuro-radiologists to identify clinical settings where its role
      is uniquely beneficial. METHODS: We performed a search of the online literature
      databases to identify studies reporting experience with FDCT in interventional
      neuro-radiology. The studies were systematically reviewed and their findings
      grouped according to specific clinical situation addressed. RESULTS: FDCT images
      allow detection of procedural complications, evaluation of low-radiopacity stents
      and assessment of endosaccular coil packing in intra-cranial aneurysms.
      Additional roles are 3-D angiography that provides an accurate depiction of
      vessel morphology with low concentrations of radiographic contrast media and a
      potential for perfusion imaging due to its dynamic scanning capability. A single
      scan combining soft tissue and angiographic examinations reduces radiation dose
      and examination time. Ongoing developments in flat detector technology and
      reconstruction algorithms are expected to further enhance its performance and
      increase this range of applications. CONCLUSION: FDCT images provide useful
      information in neuro-interventional setting. If current research confirms its
      potential for assessing cerebral haemodynamics by perfusion scanning, the
      combination would redefine it as an invaluable tool for interventional neuro
      radiology procedures. This facility and its existing capabilities of parenchymal
      and angiographic imaging would also extend its use to the triage of acute stroke
      patients.

PMID- 19859703
TI  - Netropsin binding in five duplex-dimer DNA constructs as a function of size and
      distance between binding sites: circular dichroism and absorption spectroscopy.
AB  - The optical activity induced on binding the drug netrospin (NET) in the minor
      groove of DNA is studied in five oligonucleotides (OGNs) as a function of (1) the
      size of the binding site in (5'-(GC)(2)AATT(GC)(2)-3')(2) (OGN 1a) versus (5'
      (GC)(2)AAATTT(GC)(2)-3')(2) (OGN 1b) and (2) the distance between two AATT
      binding sites in (5'-(GC)(2)AATT(GC)( x )AATT(GC)(2)-3')(2), with x = 1, 2, or 3
      (OGNs 2a, b, c, respectively). NET binding is monitored via the induced circular
      dichroism (CD) at approximately 315 nm, where the nucleic acids are optically
      inactive. The CD titrations, fit to a tight binding model, yield lower limits for
      the binding constant, K(a), >or=8 x 10(7) M(-1) for OGN 1a and >or=2 x 10(8) M(
      1) for OGNs 2a, b, c in 1 mM buffer. In 100 mM buffer, tight binding occurs in
      all five OGNs with K(a) >or= 8 x 10(7) M(-1) for OGN 1a and >or=1 x 10(8) M(-1)
      for OGNs 1b and 2a, b, c. In contrast, the elongated AAATTT binding site of OGN
      1b results in weak binding of NET in 1 mM buffer, where competing electrostatic
      interactions with the solvent environment are lower. In the constructs with two
      binding sites, the increase in flexibility introduced by intervening GC base
      pairs does not induce co-operative binding, although differences in the number of
      binding sites, n (2.05-2.65), indicate that there may be differences in the way
      NET is bound in OGNs 2a, b, c. In addition, the large shifts in the absorption
      spectra induced in bound versus free NET, and effects on the CD spectral bands at
      higher energy, are discussed in terms of electrostatic and excitonic
      interactions.

PMID- 19859706
TI  - Increased product formation induced by a directed secondary substrate limitation
      in a batch Hansenula polymorpha culture.
AB  - By the use of directed limitations of secondary substrates, the metabolic flux
      should be deflected from biomass production to product formation. In order to
      study the impact of directed limitations caused by various secondary substrates
      on the growth and product formation of the methylotrophic yeast Hansenula
      polymorpha, the cultivation systems respiration activity monitoring system
      (RAMOS) and BioLector were used in parallel. While the RAMOS device allows the
      online monitoring of the oxygen transfer rate in shake flasks, the BioLector
      enables in microtiter plates the monitoring of scattered light and the
      fluorescence intensity of the green fluorescent protein (GFP). Secondary
      substrate limitations of phosphate, potassium, and magnesium were analyzed in
      batch fermentations. The sole carbon source was either 10 g/L glucose or 10 g/L
      glycerol. The expression of the GFP gene is controlled by the FMD promoter
      (formate dehydrogenase). In batch cultures with glucose as carbon source, a
      directed limitation of phosphate increased the GFP production 1.87-fold, compared
      to phosphate unlimited conditions. Under potassium-limited conditions with
      glycerol as sole carbon source, the GFP production was 1.41-fold higher compared
      to unlimited conditions. A limitation of the substrate magnesium resulted in a
      1.22-fold increase GFP formation in the case of glycerol as carbon source.

PMID- 19859707
TI  - Pentanol isomer synthesis in engineered microorganisms.
AB  - Pentanol isomers such as 2-methyl-1-butanol and 3-methyl-1-butanol are a useful
      class of chemicals with a potential application as biofuels. They are found as
      natural by-products of microbial fermentations from amino acid substrates.
      However, the production titer and yield of the natural processes are too low to
      be considered for practical applications. Through metabolic engineering,
      microbial strains for the production of these isomers have been developed, as
      well as that for 1-pentanol and pentenol. Although the current production levels
      are still too low for immediate industrial applications, the approach holds
      significant promise for major breakthroughs in production efficiency.

PMID- 19859704
TI  - KIR3DL1/S1 genotypes and KIR2DS4 allelic variants in the AB KIR genotypes are
      associated with Plasmodium-positive individuals in malaria infection.
AB  - The importance of innate immunity in malaria has been suggested for early
      protection from maturation and multiplication of Plasmodium parasites injected
      via infected mosquitoes. In this study, the killer cell immunoglobulin-like
      receptor (KIR) genes in innate immunity were investigated for an association with
      malaria in the comparison between Plasmodium-positive and Plasmodium-negative
      Melanesian individuals in the Solomon Islands, one of the most hyperendemic
      malaria regions in the world. The higher frequency of a pair of KIR3DL1 and
      KIR2DS4 was observed in the Plasmodium-positive individuals, which led to the
      investigation of KIR3DL1/S1 genotypes in concert with KIR2DS4 allelic variants.
      The positive individuals showed the highest frequency of KIR3DL1/KIR3DS1
      heterozygosity, which might suggest the masking of activating KIR3DS1 by
      inhibitory KIR3DL1 at allelic levels to maintain the KIR3DS1-driven activation of
      natural killer cells diminished in controlling Plasmodium proliferation. The
      extended analysis with A/B genotypes further revealed the trend of parasitic
      positive individuals to be KIR3DL1/KIR3DS1 heterozygous in pair with KIR2DS4
      nondeleted variants in a set of KIR genes inheritable as the AB genotypes. To the
      best of our knowledge, this study is the first KIR investigation of the malaria
      infected population, which strengthened the potential associations of KIR with
      malaria pathogenesis. The balance of inhibitory and activating KIR3D genes
      (KIR3DL1/S1) and membrane-bound or secreted status of KIR2DS4 alleles in the
      interaction with the other KIR genes in the AB genotypes might constitute a part
      of KIR characteristics to determine resistance or susceptibility to Plasmodium
      parasitic infection.

PMID- 19859709
TI  - [Serous genital carcinoma: molecular pathogenesis and the role of tubal fimbria].
AB  - Serous carcinomas develop at various sites of the Mullerian system, in
      particular, the ovaries, the peritoneum, the uterus and the fallopian tubes.
      Currently, two distinctive molecular genetic pathways are distinguished for
      serous tumorigenesis: type I tumors are typically well differentiated and
      gradually develop from cystadenoma through borderline tumor to low grade
      carcinoma and are characterized by B-raf and K-ras mutations, whereas the poorly
      differentiated type II tumors develop from intraepithelial carcinoma and show p53
      mutations. Infrequently, p53 mutations occur as a late event in the type I
      pathway and lead to a high grade tumor phenotype. A histologically inconspicuous
      possible precursor lesion of the intraepithelial carcinoma is the p53 signature
      that shows p53 overexpression without cell cycle deregulation. Whereas in the
      ovaries both pathways may occur and develop from inclusions of the surface
      epithelium, the fallopian tube has recently been described as an important site
      for the type II pathway. High grade serous carcinomas and intraepithelial
      carcinomas of the tubal fimbria are particularly found in patients with
      BRCA1/BRCA2 germ line mutations. Since an advanced tumor stage is frequent and
      often makes the determination of the origin impossible, the term pelvic serous
      carcinoma was recently proposed for high grade serous (adeno)carcinomas involving
      multiple sites.

PMID- 19859710
TI  - [Predictive EGFR gene analyses in cytology].
AB  - EGFR mutations and EGFR gene copy number are considered as predictive markers for
      response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer
      (NSCLC).NSCLC are often diagnosed by cytology alone. The isolation or selection
      of a pure tumour cell population is critical for mutation analysis by PCR and
      sequencing in order to avoid an admixture of tumour DNA with normal DNA of
      adjacent benign cells. The collection of tumour cells is easily possible by laser
      microdissection (LMD).EGFR FISH analysis on cytological specimens with a high
      proportion of benign respiratory cells should be performed after automated
      relocation of carcinoma cells. The only hitherto established EGFR-FISH criteria
      were developed using histological specimens and cannot be applied to cytological
      specimens as such. The cell nuclei in cytological specimens are intact, while
      they are often truncated in histological specimens. Therefore, when applying the
      Colorado criteria, the rate of FISH positive results is higher in cytological
      than in histological specimens and in fact represents false positive results in
      cytology.Cytological specimens are equally well suited for EGFR gene analyses and
      FISH analysis as histological specimens. At present, the value of EGFR-FISH
      analysis is limited by the lack of validated criteria for FISH positivity.

PMID- 19859711
TI  - Anabolic androgenic steroid induced necrotising myopathy.
AB  - We describe the case of a 23-year-old gentleman who developed a severe
      generalised necrotising myopathy. Initially presenting with features of a virus
      induced polymyositis, both symptomatic and biochemical improvements were
      initially achieved with glucocorticoid-based immunosuppression. Subsequently he
      represented with evidence of severe generalised rhabdomyolysis (creatinine kinase
      peaking at 210,000 U/L). Rendered anuric from the myogloburic assault, he
      required intensive care support from the development of multi-organ failure.
      Subsequent investigations failed to demonstrate an infective, inflammatory,
      metabolic or inherited aetiology. Muscle biopsy demonstrated severe generalised
      necrotising myopathy in the notable absence of inflammation. Confidential
      discussion with the patient and relatives confirmed a suspicion of anabolic
      androgenic steroid (AAS) abuse. There is limited literature as to the toxic
      effect of AAS compounds on muscle tissue, and these tend to focus on localised
      disease. Indeed, AAS have consistently been shown in animal models to produce a
      generalised myotrophic state. Apart from the social uses of such compounds, the
      scope for their supervised use in various medical conditions has been established
      since the 1960s.

PMID- 19859712
TI  - High prevalence of anti-beta-2 glycoprotein-I and anti-prothrombin antibodies in
      adult-onset Still's disease. Comment on "Portal vein thrombosis in adult-onset
      Still's disease: a case report and literature review".

PMID- 19859714
TI  - Successful treatment of Candida discitis with 5-flucytosine and fluconazole.

PMID- 19859713
TI  - The anti-malaria agent artesunate inhibits expression of vascular endothelial
      growth factor and hypoxia-inducible factor-1alpha in human rheumatoid arthritis
      fibroblast-like synoviocyte.
AB  - Increasing evidence indicates that the anti-malarial agent artemisinin and its
      derivatives may exert anti-angiogenic effect. In the present study, we explored
      the effect of artesunate, a artemisinin derivative, on TNFalpha- and hypoxia
      induced expression of hypoxia inducible factor-1alpha (HIF-1alpha) and secretion
      of vascular endothelial growth factor (VEGF) and inteleukin-8 (IL-8) in human
      rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further
      investigated the signal mechanism by which this compound modulates HIF-1alpha,
      VEGF and IL-8 expression. RA FLS obtained from patients with active rheumatoid
      arthritis were pretreated with artesunate, and then stimulated with TNFalpha and
      hypoxia. Production of VEGF and IL-8 was measured by ELISA. Nuclear location of
      HIF-1alpha was measured by confocal fluorescence microscopy. HIF-1alpha and other
      signal transduction proteins expression was measured by Western blot. Artesunate
      decreased the secretion of VEGF and IL-8 from TNFalpha- or hypoxia-stimulated RA
      FLS in a dose-dependent manner. Artesunate also inhibited TNFalpha- or hypoxia
      induced nuclear expression and translocation of HIF-1alpha. We also showed that
      artesunate prevented Akt phosphorylation, but did not find evidence that
      phosphorylation of p38 and ERK was affected. TNFalpha- or hypoxia-induced
      secretion of VEGF and IL-8 and expression of HIF-1alpha were hampered by
      treatment with the PI3 kinase inhibitor LY294002, suggesting that inhibition of
      PI3 kinase/Akt activation might inhibit VEGF and IL-8 secretion and HIF-1alpha
      expression induced by TNFalpha or hypoxia. Our results suggest that artesunate
      inhibits angiogenic factor expression in RA FLS, and provide novel evidence that,
      as a low-cost agent, artesunate may have therapeutic potential for RA.

PMID- 19859715
TI  - One year study of efficacy and safety of infliximab in the treatment of patients
      with ocular and neurological Behcet's disease refractory to standard
      immunosuppressive drugs.
AB  - The aim of the study was to assess the long-term efficacy and safety of
      Infliximab therapy in the treatment of patients with Behcet's disease refractory
      to standard immunosuppressive agents. Twenty-one patients that did not respond to
      corticosteroids and to at least one immunosuppressant (cyclosporin, methotrexate,
      azathioprine, cyclophosphamide) for the presence of ocular and/or CNS involvement
      were enrolled. Eighteen patients completed the study up to 54 weeks. Stable doses
      of prednisone (<10 mg/day) were permitted, immunosuppressants were discontinued
      at least 4 weeks prior baseline visit. The patients received three infusions of 5
      mg/kg Infliximab (at weeks 0, 2 and 6) and then infusions of 5 mg/kg Infliximab
      every 8 weeks. At each visit data on clinical symptoms, response to therapy and
      adverse events were collected. The primary outcome of interest was to assess the
      clinical efficacy (total or partial recovery) of infliximab. Secondary end points
      were to evaluate quality of life and to monitor the safety of the drug. Eighteen
      patients achieved a total remission. Two patients achieved a partial remission
      and relapsed after 3 months from discontinuation of therapy. Infliximab was well
      tolerated throughout the study. A case of non-Hodgkin lymphoma was observed
      within 6 months. Minor side effects were headache, dizziness, tachycardia that
      regressed spontaneously and did not entail interruption. Anti-nuclear antibodies
      were not detected during the period of observation.

PMID- 19859716
TI  - Streptomyces scabiei and its toxin thaxtomin A induce scopoletin biosynthesis in
      tobacco and Arabidopsis thaliana.
AB  - Streptomyces scabiei is the predominant causal agent of common scab of potato in
      North America. The virulence of common scab-causing streptomycetes relies on
      their capacity to synthesize thaxtomins. In this study, the effects of S. scabiei
      infection and of thaxtomin A, the main toxin produced by S. scabiei, were tested
      for the elicitation of plant defense molecules in the model plants tobacco
      (Nicotiana tabacum) and Arabidopsis thaliana. Tobacco leaves infected with spores
      of S. scabiei strain EF-35 or infiltrated with purified thaxtomin A produced a
      blue fluorescent compound that was not detected in leaves infiltrated with spores
      of a S. scabiei mutant deficient in thaxtomin A biosynthesis. Thin layer
      chromatography and high performance liquid chromatography identified this
      fluorescent compound as scopoletin, a plant defense phytoalexin. Arabidopsis
      seedlings grown in liquid medium also excreted scopoletin as a reaction to S.
      scabiei and thaxtomin A. The effects of the presence of scopoletin on S. scabiei
      were also investigated. The phytoalexin scopoletin caused a slight reduction of
      bacterial growth and a severe decrease of thaxtomin A production. Scopoletin was
      shown to inhibit thaxtomin A production by repression of a gene involved in the
      toxin biosynthesis.

PMID- 19859717
TI  - Expression of the Cyanidioschyzon merolae stromal ascorbate peroxidase in
      Arabidopsis thaliana enhances thermotolerance.
AB  - The ability of the primitive red alga Cyanidioschyzon merolae to adapt to high
      temperatures was utilized to produce thermotolerant transgenic plants. C. merolae
      inhabits an extreme environment (42 degrees C, pH 2.5) and the nuclear,
      mitochondrial, and plastid genomes have been sequenced. We analyzed expressed
      sequence tag (EST) data to reveal mechanisms of tolerance to high temperatures.
      The stromal ascorbate peroxidase (CmstAPX) that scavenges reactive oxygen species
      (ROS) was expressed at high levels (4th of 4,479 entries), thus, it offers clues
      to understanding high-temperature tolerance. CmstAPX has a chloroplast transit
      peptide (cTP) and a peroxidase domain. The peroxidase domain of CmstAPX has
      deletions and insertions when compared with that of Arabidopsis thaliana stromal
      APX (AtstAPX). To clarify aspects of tolerance to oxidative and high-temperature
      stress, we produced transgenic A. thaliana plants overexpressing CmstAPX and
      AtstAPX. CmstAPX plants showed higher activities of soluble APX than those of
      wild-type and AtstAPX plants. Fluorescence signals of a GFP fusion protein,
      immuno-fluorescence, and immunogold electron microscopy showed that CmstAPX was
      localized in the stroma of chloroplasts. Compared with wild-type plants and
      AtstAPX plants, CmstAPX plants were more tolerant to oxidative stress induced by
      methylviologen (MV, 0.4 muM) and high-temperature stress (33 degrees C). CmstAPX
      plants retained the highest chlorophyll content when treated with MV and high
      temperature, and their stroma and chloroplasts remained intact in their
      chloroplasts, whereas they disintegrated in wild-type plants. Our results suggest
      that the increased activity of APX in the chloroplasts of CmstAPX plants
      increased thermotolerance by increasing ROS-scavenging capacity at high
      temperatures.

PMID- 19859718
TI  - Atypical presentation of chronic granulomatous disease in an adolescent boy with
      frontal lobe located Aspergillus abscess mimicking intracranial tumor.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is an uncommon congenital
      phagocyte disorder characterized by recurrent life-threatening infections. CGD
      generally present with recurrent suppurative infections, however, intracranial
      fungal abscess complicating CGD may cause a diagnostic problem to anyone
      unfamiliar with its clinical and radiological features. HISTORY: We report the
      case of a 16-year-old boy who was consulted with a differential diagnosis of an
      intracranial tumor. The clues of his medical history and physical examination
      made us consider the diagnosis of CGD. Cytometric dihydrorhodamine assay and
      genotyping confirmed an autosomal recessive CGD. He was successfully treated
      without any complication or sequel for 18 months follow-up period with surgery
      and interferon-gamma, in addition with, liposomal amphotericin B and voriconazole
      that were found to be sensitive to the Aspergillus fumigates, which had been
      grown from the culture of the abscess cavity. DISCUSSION: We discuss the
      pathogenesis, radiological techniques, and management of cerebral Aspergillus
      abscess in a patient with CGD. CONCLUSION: Presentation of CGD with a cerebral
      Aspergillus abscess, mimicking a brain tumor is extremely rare in children;
      clinicians and neurosurgeons must be aware. The best management modality for
      cerebral Aspergillus abscess is to be vigilant about the disease, whereas
      adjuvant surgical and medical therapy with a close follow-up must be warranted
      for all cases.

PMID- 19859719
TI  - Zinc deficiency impairs wound healing of colon anastomosis in rats.
AB  - BACKGROUND: Anastomotic leakage is a relevant surgical complication. The aim of
      the study was to investigate the influence of a controlled preoperative zinc
      deficiency on the extracellular matrix composition of colon anastomosis.
      MATERIALS AND METHODS: Forty male Wistar rats were randomized to either a zinc
      deficiency group (n = 20) or a control group (n = 20). In each animal, a
      transverse colonic end-to-end anastomosis was performed. On postoperative day 7,
      the surface of the mucosal villi, expression of matrix metalloproteinases (MMP)
      2, 8, 9, and 13, and both the number of proliferating cells (Ki67) and apoptotic
      cells, as well as the collagen types I/III ratio were analyzed. Within the
      anastomotic area the mesenterial region and the antimesenterial region were
      analyzed separately. RESULTS: In each group, one anastomotic leakage was
      detected. Expression of both MMP 2, 9, and 13 was significantly higher, and
      expression of Ki67 was significantly reduced in the zinc deficient group both
      mesenterial and antimesenterial. The collagen types I/III ratio was reduced in
      the zinc deficiency group by trend, without statistical significance neither
      mesenterial nor antimesenterial. Likewise, zinc deficiency affected neither the
      expression of MMP 8 nor the rate of apoptotic cells, respectively. Analyses of
      the surface of the mucosal villi revealed no significant differences comparing
      the groups with neither mesenterial nor antimesenterial. CONCLUSIONS: Our study
      constitutes the known negative effect of zinc deficiency on wound healing. Zinc
      deficiency significantly increased the activity of MMPs (2, 9, and 13), caused a
      reduced collagen type I/III ratio, and delayed cell proliferation and quality of
      intestinal wound healing.

PMID- 19859720
TI  - Rectal cancer: quo vadis, neoadjuvant and adjuvant (chemo) radiotherapy?

PMID- 19859721
TI  - Prediction of histology and invasive depth of colorectal neoplasia based on
      morphology of surface depression using magnifying chromocolonoscopy.
AB  - BACKGROUND AND STUDY AIMS: Estimation of histology and depth of invasion in early
      colorectal neoplasia is essential for patient treatment. We therefore conducted a
      prospective study to examine whether the morphology of depression area contained
      at the surface of colorectal neoplasia can be used for predicting the histology
      and invasive depth. METHODS: A series of 228 consecutive patients with 296
      colorectal lesions were studied. All lesions were evaluated by magnifying
      chromocolonoscopy. Surface depression contained in the lesions was noted and the
      depressive morphology was further divided into two subgroups of type I and type
      II. All of the lesions were resected endoscopically or surgically and examined
      histologically for comparison. RESULTS: A total of 296 lesions were evaluated, of
      which 66 (22.3%) contained an area of central depression, including 43 in
      nonpolypoid (flat and depressed) lesions (66%) and 23 in polypoid (10%). The
      overall accuracy of depressive morphology for distinction between low-grade
      dysplasia and high-grade dysplasia/invasive cancer, and between m-sm1 and sm2-sm3
      was 86.4% and 84.8%, respectively. CONCLUSIONS: Depression was predominantly
      contained in nonpolypoid colorectal neoplasia. Morphology of depression observed
      by magnifying chromocolonoscopy could be used as a complementary method to assess
      the degree of atypia and invasive depth in colorectal neoplasia.

PMID- 19859722
TI  - Stent or surgery for incurable obstructive colorectal cancer: an individualized
      decision.
AB  - INTRODUCTION: In the setting of stage-IV obstructive colorectal cancer, self
      expanding metallic stents (SEMS) placement and palliative surgery may be
      appropriate options. The aim of the present study is to evaluate the long-term
      results of surgery compared with stent implantation and to identify patients in
      whom one of these options can provide more benefit. MATERIALS AND METHODS: From
      November 2000 to November 2008, 98 patients with incurable stage-IV colorectal
      cancer were treated with palliative surgery (n=53) or SEMS (n=45). Data were
      recorded with respect to age, gender, tumor location, carcinoembryogenic antigen,
      ASAclass, presence of metastatic disease in one or multiple organs, volume of
      liver metastases, urgency of the procedure and treatment with chemotherapy.
      Comparison between surgery and stent placement was performed for all group and
      for patients who received and did not receive chemotherapy. RESULTS: Both groups
      were comparable regarding age, ASA-class, chemotherapy treatment, tumor location
      and presence of metastatic disease in one or multiple organs but not in gender,
      rate of urgent procedures, abnormal CEA and of volume of liver metastases >25%.
      Survival in surgical group was significantly higher (11.9 vs 7.3 months; log-rank
      test, p = 0.002). SEMS group had lower early morbidity, hospital stay and stoma
      creation. For patients who received chemotherapy, surgery provided benefit in
      survival (6.8 vs 3.9 months; log-rank test, p = 0.101); in this subgroup, long
      term complications from the primary tumour were more common in stented group, and
      time to chemotherapy was longer in the group of surgery. No differences in
      survival were shown in patients who did not receive chemotherapy. CONCLUSION:
      Stent placement offers advantages regarding early morbidity, hospital stay and
      stoma creation. Surgery offers a benefit in survival in patients who receive
      chemotherapy but not in non-candidates to chemotherapy.

PMID- 19859723
TI  - The point prevalence of otitis media with effusion among primary school children
      in Western Sicily.
AB  - The objective of this study is to identify the prevalence of otitis media with
      effusion (OME) in primary school children and to value the possible predisposing
      factors focusing on relationship between allergy and OME in Western Sicily. 2,097
      children attending primary school were screened from September 2006 to June 2007
      in Sciacca. Children underwent pneumatic otoscopy, skin tests, tympanogram and
      acoustic reflex tests. Audiogram was performed if the child had a type B or a
      type C tympanogram. The criteria for diagnosis of OME were: documented persistent
      middle ear effusion by otoscopic examination for a minimum of 3 months, presence
      of B or C tympanogram, absence of ipsilateral acoustic reflex and a conductive
      hearing loss greater than 25 dB at any one of the frequencies from 250 Hz to 4
      kHz. OME was identified in 143 children, in 61 of whom OME was unilateral and in
      82 of whom it was bilateral. The overall prevalence of OME was 6.8%, with a
      maximum prevalence of 12.9% between 5 and 6 years of age. By increasing age, the
      prevalence of OME decreased. Also, we found a higher prevalence rate of OME in
      children with positive skin tests (62.9%) than those with negative skin tests
      (37.1%). The present study evidences the high social impact of OME, whose
      prevalence is directly correlated to age and atopy. Moreover, our finding
      supports the literature data that climatic and environmental factors may also
      have a role in the occurrence of OME.

PMID- 19859725
TI  - Dental age estimation in Spanish and Venezuelan children. Comparison of Demirjian
      and Chaillet's scores.
AB  - Orthopantomographs taken from 308 Spanish Caucasian and 200 Venezuelan Amerindian
      children, aged between 2 and 18 years, were analysed following the Demirjian's
      method. The aims of this study were to test the applicability of the Demirjian's
      method to two different sample populations, and to develop age prediction models
      for both populations using the original French Canadian scores described by
      Demirjian (1976) and the new multi-ethnic dental scores proposed by Chaillet et
      al. (2005) when the ethnic origin is unknown. Results showed that despite the
      good correlation between dental and chronological age, Demirjian's method
      overestimates the age in the Spanish Caucasian sample using both scores, the mean
      overestimation being higher when the Demirjian's scores were used than when the
      Chaillet's scale was applied. In the Venezuelan Amerindian sample, the opposite
      was found: Demirjian's method underestimates the age using both scores, the
      underestimation being higher when the Chaillet's scale was applied than when
      Demirjian's scale was used. New graphs were produced to convert the maturity
      scores to dental age for Spanish and Venezuelan children. With these graphs, the
      Demirjian's scores showed to be inadequate after the age of 12 in both
      populations, while Chaillet's scores offered useful information until 14 years of
      age.

PMID- 19859726
TI  - A novel and an effective analytical approach for the LC-MS determination of ethyl
      glucuronide and ethyl sulfate in urine.
AB  - An alternative liquid chromatography-mass spectrometry (LC-MS) method based on no
      discharge (ND) atmospheric pressure chemical ionization (APCI) was developed for
      the simultaneous determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS)
      in urine in negative ion conditions. Abundant [M-H](-) species of EtG and EtS
      were obtained, allowing to reach limits of quantification (0.1 microg/ml for both
      analytes), accuracy, and precision comparable to those proposed in the
      literature. Additionally, the LC-ND-APCI-MS method proved to be reliable,
      requiring little maintenance even when high throughput analyses (i.e., 6,000
      samples per year) were required.

PMID- 19859727
TI  - Changes of extracellular matrix of the cornea in diabetes mellitus.

PMID- 19859728
TI  - Changes in physical performance among construction workers during extended
      workweeks with 12-hour workdays.
AB  - PURPOSE: To investigate changes of physical performance during long working hours
      and extended workweeks among construction workers with temporary accommodation in
      camps. METHODS: Nineteen construction workers with 12-h workdays and extended
      workweeks participated. Physical performance in the morning and evening of the
      second and eleventh workdays was tested by endurance, ability to react to a
      sudden load, flexibility of the back, handgrip strength and sub-maximal HR during
      a bicycle test. HR was registered throughout two separate workdays. RESULTS: HR
      during each of the two separate workdays corresponded to a relative workload of
      25%. Sub-maximal HR was lower, reaction time faster and handgrip strength higher
      in the end of each test day. In the end of the work period, sub-maximal HR was
      lower, reaction time faster and sitting balance was better. CONCLUSION: No trends
      of decreased physical performance were found after a workday or a work period.

PMID- 19859729
TI  - Resistance training improves femoral artery endothelial dysfunction in aged rats.
AB  - Although endurance exercise improves age-associated endothelial dysfunction, few
      studies have examined the effects of resistance training and the potential
      molecular mechanisms involved in altering vascular reactivity with age. Young (9
      months) and aged (20 months) male, Fisher 344 rats were divided into four groups:
      Young Sedentary (YS, n = 14), Young Trained (YT, n = 10), Aged Sedentary (AS, n =
      12), and Aged Trained (AT, n = 10). Resistance training consisted of climbing a 1
      m wire ladder, at an 85 degrees angle, 3 days/week for 6 weeks with increasing
      weight added to the tail. Endothelial function in femoral arteries was determined
      by constructing acetylcholine dose-response curves on a wire myograph. Femoral
      artery phospho-Ser1179-eNOS, eNOS and Hsp90 expression were evaluated by Western
      blot. Acetylcholine-induced vasorelaxation was significantly (P < 0.05) impaired
      in AS compared to YS and YT but not AT compared to YS and YT. Phospho-Ser1179
      eNOS and eNOS were elevated (P < 0.05) in aged animals but not changed with
      resistance training. Resistance training increased Hsp90 levels in both young and
      old animals. Therefore, resistance training improves age-associated endothelial
      dysfunction in femoral arteries without changes in eNOS phosphorylation and
      expression. Increased Hsp90 expression, a regulator of eNOS activity and
      coupling, suggests a potential mechanism for this improvement.

PMID- 19859730
TI  - What is critical for plant thermogenesis? Differences in mitochondrial activity
      and protein expression between thermogenic and non-thermogenic skunk cabbages.
AB  - Thermogenesis during the blooming of inflorescence is found in several but not
      all aroids. To understand what is critical for thermogenesis, we investigated the
      difference between thermogenic and non-thermogenic skunk cabbages (Symplocarpus
      renifolius and Lysichiton camtschatcensis), which are closely related in
      morphology and phylogeny. Critical parameters of mitochondrial biogenesis,
      including density, respiratory activity, and protein expression were compared
      between these two species. Mitochondrial density, respiratory activity, and the
      amount of alternative oxidase (AOX) in L. camtschatcensis spadix mitochondria
      were lower than in S. renifolius spadix mitochondria, while the level of
      uncoupling protein (UCP) was higher. AOX and UCP mRNAs in L. camtschatcensis were
      constitutively expressed in various tissues, such as the spadix, the spathe, the
      stalk, and the leaves. cDNA encoding two putative thermogenic proteins, AOX and
      UCP were isolated from L. camtschatcensis, and their primary structure was
      analyzed by multiple alignment and phylogenetic tree reconstruction. AOX and UCP
      protein of two the skunk cabbage species are closely related in structure,
      compared with other isoforms in thermogenic plants. Our results suggest that
      mitochondrial density, respiratory activity, and protein expression, rather than
      the primary structure of AOX or UCP proteins, may play critical roles in
      thermogenesis in plants.

PMID- 19859731
TI  - Broad-spectrum disease resistance to necrotrophic and biotrophic pathogens in
      transgenic carrots (Daucus carota L.) expressing an Arabidopsis NPR1 gene.
AB  - The development of transgenic plants highly resistant to a range of pathogens
      using traditional signal gene expression strategies has been largely ineffective.
      Modification of systemic acquired resistance (SAR) through the overexpression of
      a controlling gene such as NPR1 (non-expressor of PR genes) offers an attractive
      alternative for augmenting the plants innate defense system. The Arabidopsis (At)
      NPR1 gene was successfully introduced into 'Nantes Coreless' carrot under control
      of a CaMV 35S promoter and two independent transgenic lines (NPR1-I and NPR1-XI)
      were identified by Southern and Northern blot hybridization. Both lines were
      phenotypically normal compared with non-transformed carrots. Northern analysis
      did not indicate constitutive or spontaneous induction in carrot cultures of SAR
      related genes (DcPR-1, 2, 4, 5 or DcPAL). The duration and intensity of
      expression of DcPR-1, 2 and 5 genes were greatly increased compared with controls
      when the lines were treated with purified cell wall fragments of Sclerotinia
      sclerotiorum as well as with 2,6-dichloroisonicotinic acid. The two lines were
      challenged with the necrotrophic pathogens Botrytis cinerea, Alternaria radicina
      and S. sclerotiorum on the foliage and A. radicina on the taproots. Both lines
      exhibited 35-50% reduction in disease symptoms on the foliage and roots when
      compared with non-transgenic controls. Leaves challenged with the biotrophic
      pathogen Erysiphe heraclei or the bacterial pathogen Xanthomonas hortorum
      exhibited 90 and 80% reduction in disease development on the transgenic lines,
      respectively. The overexpression of the SAR controlling master switch in carrot
      tissues offers the ability to control a wide range of different pathogens, for
      which there is currently little genetic resistance available.

PMID- 19859733
TI  - Clinical practice. Later orthodontic complications caused by risk factors
      observed in the early years of life.
AB  - Primary preventive strategies for oral health are an essential public health
      priority. Paediatricians have frequent contact with families during routine
      preventive visits in the child's first few years of life and are in an ideal and
      unique position, to advise families about the prevention of oral diseases in
      their children. Primary prevention is always recommended in very young children,
      to promote positive outcomes during childhood and later adulthood. The knowledge
      paediatricians acquire about orofacial growth may enhance the implementation and
      eventual success of a preventive programme. In view of the widespread lack of any
      orthodontic knowledge amongst paediatricians, this paper describes most common
      and distinctive symptoms appearing frequently in the early stages of a child's
      development that are easily detectable by clinicians. It is difficult to define
      preventive strategies to prevent malocclusion owing to its multifactorial origin.
      There are some recognised behaviours, however, that should be discouraged to
      allow for ideal craniofacial development and some that require early referral to
      the orthodontist. The following disorders are easily diagnosed by the
      paediatrician or parents and represent conditions in which early intervention
      might be appropriate to prevent future possible orofacial dysfunction: different
      sucking habits persisting beyond 3 years of age, mouth breathing and significant
      deviations from established teeth eruption norms. It is suggested that early
      referral to a paediatric dentist or orthodontist is indicated when any of these
      conditions are observed. In general, measures to prevent malocclusion should be
      based on providing good incentives to promote normal growth and development of
      the face and the elimination of potential interferences that may harm these
      processes.

PMID- 19859732
TI  - Precursors of endometrial and ovarian carcinoma.
AB  - This review discusses precursor lesions of endometrial and ovarian carcinoma with
      an emphasis on the unique molecular alterations that have led to the development
      of binary classification schemes for tumors of both the endometrium and ovary.
      While such a system is well established for endometrial carcinoma, only recently
      has a binary classification scheme been proposed for ovarian carcinoma. For both,
      the morphologic and molecular genetic-defining characteristics of their
      respective precursor lesions are described in detail. Furthermore, similarities
      and differences of the precursor lesions of specific tumors of these two genital
      tract organs are also addressed with a brief discussion of the clinical
      implications of their diagnosis.

PMID- 19859734
TI  - A 4-year-old boy presenting with recurrent croup.
AB  - Croup is common in children but recurrent croup is unusual. A 4-year-11-month-old
      boy presented with recurrent croup. Physical examination revealed decreased
      breath sounds over left lower chest. Chest x-ray disclosed segmental atelectasis
      over left lower chest and a mass shadow over mediastinum.

PMID- 19859735
TI  - Long-term follow-up and a detailed prognostic analysis of patients with
      oropharyngeal cancer treated with radiotherapy.
AB  - PURPOSE: To find a prognostic factor for patients with oropharyngeal cancer (OPC)
      who were followed for long term after definitive radiotherapy. METHODS: OPC
      patients that had been treated with radiotherapy at our institution were
      reviewed. Sex, age, performance status (PS), subsite, disease stage, T-stage, N
      stage, RT dose, concurrent chemotherapy, the duration of RT, hemoglobin
      concentration before any treatment, and a double cancer were assessed for their
      impact on overall survival (OS) and locoregional control (LRC). RESULTS: Among a
      total of 141 patients enrolled into this retrospective study, the disease of most
      patients (81%) was stage III or IV. The median follow-up time of the surviving
      patients was 56 months (range 5-175 months). Radiotherapy was administered in
      conventional fractionation, and the median RT dose was 66 Gy. Most patients (90%)
      received systemic chemotherapy. The 5-year estimates of progression-free
      survival, LRC, and OS were 66.0, 72.7, and 65.1%, respectively. In the univariate
      analysis, LRC and OS in the lateral wall at the primary site, T-stage <or=3, and
      PS <or=1 groups were significantly superior to those in the other groups, and OS
      in age <or=60 or the hemoglobin level >13.0 g/dL groups were also significantly
      superior to those in the other groups. In the multivariate analysis, age and T
      stage remained significant factors for OS. CONCLUSIONS: Primary radiotherapy was
      recommended for OPC patients with the lateral wall at the primary site because of
      good LRC. The treatment method to the older population and T4 tumor is future
      tasks.

PMID- 19859737
TI  - Bioassay-guided isolation and identification of active compounds from Fructus
      Arctii against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius
      auratus).
AB  - Dactylogyrus intermedius is a significant monogenean parasite on the gills of
      cyprinid fishes and can cause serious problem in fish aquaculture. In the present
      study, bioassay-guided fractionation was employed to identify the active
      compounds from Fructus Arctii against D. intermedius. Five solvents (petroleum
      ether, chloroform, ethyl acetate, ethanol, and water) were applied for the
      extraction of Fructus Arctii. Among them, only the chloroform extract exhibited
      promising anthelmintic efficacy and therefore, subjected to the further isolation
      and purification using various chromatographic techniques. Two compounds showing
      potent activity were obtained and identified by spectral data (infrared, nuclear
      magnetic resonance, and mass spectrometry) as: arctigenin (1) and arctiin (2).
      They were found to be significantly effective against D. intermedius with median
      effective concentration (EC(50)) values of 0.62 and 3.55 mg L(-1), respectively.
      Arctigenin exhibited higher activity as compared with the positive control
      mebendazole with an EC(50) value of 1.25 mg L(-1). The 48-h acute toxicity tests
      (LC(50)) of arctigenin and arctiin were found to be 8.47 and 14.14 mg L(-1) for
      goldfish, respectively. These results provided evidence that the studied plant
      extract, as well as the isolated compounds, might be potential sources of new
      antiparasitic drug for the control of Dactylogyrus.

PMID- 19859738
TI  - Molecular cloning and characterization of a novel serpin gene of Clonorchis
      sinensis, highly expressed in the stage of metacercaria.
AB  - The serpins are a superfamily of proteins (350-500 amino acids in size) that fold
      into a conserved structure. From about 3,475 unigenes of Clonorchis sinensis
      metacercaria, a novel gene-encoding serpin was identified and characterized. The
      opening reading frame is 1,149 bp encoding 382 amino acids. The deduced amino
      acid sequence shows high identity to previously reported serpins from C. sinensis
      and other helminthic parasites. A typical serpin signature was found by motif
      search. The recombinant C. sinensis serpin protein (rCsproSERPIN) was produced
      and purified. Semiquantitative analysis revealed that the transcripts of this
      serpin gene in metacercaria were much higher than that in adult worms and that
      the corresponding band of serpin protein in the crude soluble antigen of
      metacercaria probed by rat anti-CsproSERPIN serum was also much clearer compared
      with that of adult, suggesting that it plays an important role in the stage of C.
      sinensis metacercaria. Although we are not much clear about the detailed function
      of this serpin protein, the study that proteinase initiates metacercaria
      excystment gives a clue that it may participate in the encystment of cercaria.

PMID- 19859739
TI  - Comparison of microscopic examination, rK39, and PCR for visceral leishmaniasis
      diagnosis in Turkey.
AB  - The laboratory diagnosis of visceral leishmaniasis is based on microscopic
      examination, culture, serological tests, and molecular methods. In this study, we
      examined 50 blood specimens from suspected visceral leishmaniasis patients by
      microscopic examination, recombinant antigen dipstick test (rK39), and polymerase
      chain reaction (PCR) in the University of Cukurova, Faculty of Medicine,
      Parasitology Department in Turkey. We calculated the sensitivity-specificity and
      positive-negative predictive values for these diagnostic tests. We found that
      positive predictive value of microscopy examination, rK39 dipstick test, and PCR
      were 20%, 24%, and 58% for visceral leishmaniasis, respectively. When we compared
      polymerase chain reaction, recombinant antigen dipstick test, and microscopic
      examination for visceral leishmaniasis diagnosis, the polymerase chain reaction
      is more sensitive (100%) than recombinant antigen dipstick test and microscopy
      examination.

PMID- 19859740
TI  - Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter
      haplotypes.
AB  - Nitric oxide (NO) mediates host resistance to severe malaria and other infectious
      diseases. NO production and mononuclear cell expression of the NO producing
      enzyme-inducible nitric oxide synthase (NOS2) have been associated with
      protection from severe falciparum malaria. The purpose of this study was to
      identify single nucleotide polymorphisms (SNPs) and haplotypes in the NOS2
      promoter, to identify associations of these haplotypes with malaria severity and
      to test the effects of these polymorphisms on promoter activity. We identified 34
      SNPs in the proximal 7.3 kb region of the NOS2 promoter and inferred NOS2
      promoter haplotypes based on genotyping 24 of these SNPs in a population of
      Tanzanian children with and without cerebral malaria. We identified 71
      haplotypes; 24 of these haplotypes comprised 82% of the alleles. We determined
      whether NOS2 promoter haplotypes were associated with malaria severity in two
      groups of subjects from Dar es Salaam (N = 185 and N = 250) and in an inception
      cohort of children from Muheza-Tanga, Tanzania (N = 883). We did not find
      consistent associations of NOS2 promoter haplotypes with malaria severity or
      malarial anemia, although interpretation of these results was potentially limited
      by the sample size of each group. Furthermore, cytokine-induced NOS2 promoter
      activity determined using luciferase reporter constructs containing the proximal
      7.3 kb region of the NOS2 promoter and the G-954C or C-1173T SNPs did not differ
      from NOS2 promoter constructs that lacked these polymorphisms. Taken together,
      these studies suggest that the relationship between NOS2 promoter polymorphisms
      and malaria severity is more complex than previously described.

PMID- 19859742
TI  - Woody-grass ratios in a grassy arid system are limited by multi-causal
      interactions of abiotic constraint, competition and fire.
AB  - Predicting changes in vegetation structure in fire-prone arid/semi-arid systems
      is fraught with uncertainty because the limiting factors to coexistence between
      grasses and woody plants are unknown. We investigated abiotic and biotic factors
      influencing boundaries and habitat membership in grassland (Triodia or 'spinifex'
      grassland)-shrubland (Acacia aneura or 'mulga' shrubland) mosaics in semi-arid
      central Australia. We used a field experiment to test for the effects of: (1)
      topographic relief (dune/swale habitat), (2) adult neighbour removal, and (3)
      soil type (sand/clay) on seedling survival in three shrub and two grass species
      in reciprocal field plantings. Our results showed that invasion of the shrubland
      (swale) by neighbouring grassland species is negated by abiotic limitations but
      competition limits shrubland invasion of the grassland (dune). All species from
      both habitats had significantly reduced survival in the grassland (dune) in the
      presence of the dominant grass (Triodia) regardless of soil type or shade.
      Further, the removal of the dominant grass allowed the shrubland dominant (A.
      aneura) to establish outside its usual range. Seedling growth and sexual
      maturation of the shrubland dominant (A. aneura) was slow, implying that repeated
      fire creates an immaturity risk for this non-sprouter in flammable grassland. By
      contrast, rapid growth and seed set in the grassland shrubs (facultative
      sprouters) provides a solution to fire exposure prior to reproductive onset. In
      terms of landscape dynamics, we argue that grass competition and fire effects are
      important constraints on shrubland patch expansion, but that their relative
      importance will vary spatially throughout the landscape because of spatial and
      temporal rainfall variability.

PMID- 19859743
TI  - Preparation of a composite film electrochemically deposited with chitosan and
      gold nanoparticles for the determination of alpha-1-fetoprotein.
AB  - A novel amperometric immunosensor based on chitosan-gold nanoparticles (Chit
      GNPs) composite film and thionine (Thi) was prepared for the determination of
      alpha-1-fetoprotein (AFP). The immunosensor was prepared by electro-depositing a
      Chit-GNPs composite matrix on the surface of the glass carbon electrode, then Thi
      was immobilized onto the Chit-GNPs film using glutaraldehyde as a cross-linker.
      Furthermore, the GNPs were chemisorbed onto Thi film for immobilization of alpha
      1-fetoprotein antibody. The procedure of the immunosensor was characterized by
      means of cyclic voltammograms. The performance and influencing factors of the
      resulting immunosensor were studied in details. Under optimal conditions, the
      immunosensor was highly sensitive to AFP and the linear range covered from 0.40
      to 200.0 ng mL(-1) with a detection limit of 0.24 ng mL(-1) at three times
      background noise. Moreover, the simple and controllable electro-deposition method
      overcame the irreproducibility for preparing Chit-based immunosensor systems and
      the proposed immunosensor displayed a satisfactory reproducibility and stability.

PMID- 19859741
TI  - Ectopic synaptic ribbons in dendrites of mouse retinal ON- and OFF-bipolar cells.
AB  - The ectopic distribution of synaptic ribbons in dendrites of mouse retinal
      bipolar cells was examined by using genetic ablation of metabotropic glutamate
      receptor subtype 6 (mGluR6), electron microscopy, and immunocytochemistry.
      Ectopic ribbons were observed in dendrites of rod and ON-cone bipolar cells in
      the mGluR6-deficient mouse but not in those of wild-type mice. The number of rod
      spherules facing the ectopic ribbons in mGluR6-deficient rod bipolar dendrites
      increased gradually during early growth and reached a plateau level of about 20%
      at 12 weeks. These ectopic ribbons were immunopositive for RIBEYE, a ribbon
      specific protein, but the associated vesicles were immunonegative for
      synaptophysin, a synaptic-vesicle-specific protein. The presence of ectopic
      ribbons was correlated with an increase in the roundness of the invaginating
      dendrites of the rod bipolar cells. We further confirmed ectopic ribbons in
      dendrites of OFF-cone bipolar cells in wild-type retinas. Of the four types of
      OFF-cone bipolar cells (T1-T4), only the T2-type, which had a greater number of
      synaptic ribbons at the axon terminal and a thicker axon cylinder than the other
      types, had ectopic ribbons. Light-adapted experiments revealed that, in wild-type
      mice under enhanced-light adaptation (considered similar to the mGluR6-deficient
      state), the roundness in the invaginating dendrites and axon terminals of rod
      bipolar cells increased, but no ectopic ribbons were detected. Based on these
      findings and known mechanisms for neurotransmitter release and protein
      trafficking, the possible mechanisms underlying the ectopic ribbons are discussed
      on the basis of intracellular transport for the replenishment of synaptic
      proteins.

PMID- 19859744
TI  - Enhancement of human granulocyte-colony stimulating factor production in
      recombinant E. coli using batch cultivation.
AB  - Development of inexpensive and simple culture media is always favorable for
      recombinant protein over-expression in E. coli. The effects of medium composition
      on the production of recombinant human granulocyte-colony stimulating factor (rh
      GCSF) were investigated in batch culture of E. coli BL21 (DE3) [pET23a-hgcsf].
      First, the optimum medium for production of rh-GCSF was determined; and, then it
      was shown that mixture of amino acid addition at induction time, which was
      determined on the basis of amino acids frequency in the recombinant protein,
      increases recombinant protein expression level significantly. Furthermore, the
      effect of glucose concentration on productivity of rh-GCSF was investigated; 20
      g/l of glucose will result in maximum attainable biomass and rh-GCSF in this
      process. At optimum conditions, a cell dry weight of 10.5 g/l, an expression
      level of about 35% of total cellular protein, rh-GCSF concentration of 1.75 +/-
      0.1 g/l, and overall rh-GCSF yield of 165 +/- 5 mg/g were obtained.

PMID- 19859745
TI  - Preference of place for end-of-life cancer care and death among bereaved Japanese
      families who experienced home hospice care and death of a loved one.
AB  - PURPOSE: The aim of this study was to clarify factors related to the preference
      of place for end-of-life cancer care and death, from the perspective of the
      bereaved family. METHODS: In June 2007, in Japan, a cross-sectional anonymous
      questionnaire, which included a well-validated scale of component factors of
      hospice outcome, was administered to the bereaved family members (N = 294) of
      cancer patients who had died at home at least 6 months ago. Participants were
      recruited from 14 home hospices across the nation. We asked the preference of
      place for end-of-life care and death. RESULTS: Fifty-eight percent of
      participants preferred home settings for end-of-life care and 68% preferred to
      die at home. Multivariate logistic regression identified: (1) males, participant
      who had other caregivers, a higher-good death concept, and those who experienced
      mastery as a consequence of caregiving were more likely to prefer home for end-of
      life cancer care and (2) males, participant who had other caregivers, and
      experienced reprioritization as a consequence of caregiving and those who were
      enrolled in home hospice services for more than 60 days were more likely to
      prefer to die at home. CONCLUSIONS: Home hospice services need to be developed in
      Japan so that family support programs can be initiated early enough to support
      the family burden of household maintenance and caring for the patient. Quality
      improvement of home hospice services will support patients and families through
      end-of-life care and facilitate a good death at home.

PMID- 19859746
TI  - Natural course of HCV infection in childhood cancer survivors.
AB  - GOALS OF WORK: To describe the course of hepatitis C in a cohort of 105 survivors
      after childhood cancer. PATIENTS AND METHODS: Data on chemo/radiotherapy,
      clinical status, serial alanine aminotransferase (ALT) evaluation, and
      virological parameters after the end of treatment were collected for each
      patient. Liver biopsies, when performed, were centrally evaluated by a
      pathologist. MAIN RESULTS: All patients were alive at the end of follow-up and
      did not show hepatic insufficiency. ALT evaluation along the entire follow-up
      showed a moderate (87%) or a remarkable (13%) cytolytic pattern. Young age at
      diagnosis, hematopoietic stem cell transplantation, and duration of infection
      significantly correlate with a worse hepatic activity. Type of tumor and chemo
      and/or radiotherapy regimens did not influence the pattern of hepatic cytolysis.
      Liver biopsy, centrally reviewed in 30% of the cohort, showed one case of
      cirrhosis and mild fibrosis in 71% of the group. Higher degrees of fibrosis did
      not seem to be related to any exposition to chemo/radiotherapy but correlated
      significantly with the more remarkable cytolytic course. CONCLUSIONS: The outcome
      of hepatitis C in our patients is comparable to the one described in European
      cohorts of adult cancer survivors and perinatally infected subjects.
      Nevertheless, progression to high degrees of hepatic damage has to be monitored
      by a careful follow-up.

PMID- 19859747
TI  - Spontaneous and idiopathic chronic spinal epidural hematoma:  two case reports
      and review of the literature.

PMID- 19859749
TI  - Gallery of uncommon orthopedic implants: a guide for emergency radiologist.
AB  - The purpose of this gallery of orthopedic implants was to provide a reference for
      emergency radiologists to quickly identify uncommon devices in the shoulders,
      hips, and extremities. The cases presented in this exhibit will include unusual
      arthroplasties and prostheses as well as bone graft implants (including allograft
      and autograft). Bone grafts are frequently used for the treatment of bone
      defects, which may be caused by trauma, infection, or avascularity. Autogenous
      cancellous, corticocancellous, or cortical bone grafts are often used, either
      free or vascularized. Alternative bone graft substitutes are also used. An
      obvious complication of bone grafts is the failure of incorporation. Joint
      arthroplasty is the most frequently performed orthopedic procedure after fracture
      fixation. Major indications include degenerative joint disease, inflammatory
      arthropathy, avascular necrosis, and complicated fractures. Custom orthopedic
      implants are frequently used for less common indications or for patients with
      bone tumors. The common hardware complications are infections, loosening, small
      particle disease/osteolysis, periprosthetic fracture, hardware fracture or
      dislocation, and recurrent disease, especially in patients with tumors. Many of
      the devices used by orthopedic surgeons are infrequently seen in everyday
      radiology practice. With such variations, correct recognition of the prosthetic
      devices and their complications is very important. The goal of this exhibit was
      to familiarize the radiologist with both the normal and abnormal appearance of
      many atypical orthopedic implants. It is important to understand the purpose and
      proper function of a device, but not necessarily important to describe every
      device by its proper brand name. Although this exhibit is not meant to be
      inclusive of every unusual orthopedic implant, we will present multiple examples
      of orthopedic hardware involving the shoulder, humerus, elbow, forearm, wrist,
      hand, pelvis, hip, femur, knee, tibia, ankle, and foot that are not likely seen
      in everyday practice.

PMID- 19859750
TI  - Relationship between vibrations and dynamical heterogeneity in a model glass
      former: extended soft modes but local relaxation.
AB  - We study the relation between short-time vibrational modes and long-time
      relaxational dynamics in a kinetically constrained lattice gas with harmonic
      interactions between neighbouring particles. We find a correlation between the
      location of the low- (high-) frequency vibrational modes and regions of high
      (low) propensity for motion. This is similar to what was observed in continuous
      force systems, but our interpretation is different: in our case relaxation is due
      to localised excitations which propagate through the system; these localised
      excitations act as background disorder for the elastic network, giving rise to
      anomalous vibrational modes. Our results provide an example whereby a correlation
      between spatially extended low-frequency modes and high-propensity regions does
      not imply that relaxational dynamics originates in extended soft modes but rather
      belies their common origin. We consider other measures of elastic heterogeneity,
      such as non-affine displacement fields and mode localisation lengths, and discuss
      implications of our results to interpretations of dynamic heterogeneity more
      generally.

PMID- 19859751
TI  - Modelling apical constriction in epithelia using elastic shell theory.
AB  - Apical constriction is one of the fundamental mechanisms by which embryonic
      tissue is deformed, giving rise to the shape and form of the fully-developed
      organism. The mechanism involves a contraction of fibres embedded in the apical
      side of epithelial tissues, leading to an invagination or folding of the cell
      sheet. In this article the phenomenon is modelled mechanically by describing the
      epithelial sheet as an elastic shell, which contains a surface representing the
      continuous mesh formed from the embedded fibres. Allowing this mesh to contract,
      an enhanced shell theory is developed in which the stiffness and bending tensors
      of the shell are modified to include the fibres' stiffness, and in which the
      active effects of the contraction appear as body forces in the shell equilibrium
      equations. Numerical examples are presented at the end, including the bending of
      a plate and a cylindrical shell (modelling neurulation) and the invagination of a
      spherical shell (modelling simple gastrulation).

PMID- 19859752
TI  - The effect of Debina grapevine indigenous yeast strains of Metschnikowia and
      Saccharomyces on wine flavour.
AB  - The spontaneous alcoholic fermentation of grape must is a complex microbiological
      process involving a large number of various yeast species, to which the flavour
      of every traditional wine is largely attributed. Whilst Saccharomyces cerevisiae
      is primarily responsible for the conversion of sugar to alcohol, the activities
      of various non-Saccharomyces species enhance wine flavour. In this study,
      indigenous yeast strains belonging to Metschnikowia pulcherrima var. zitsae as
      well as Saccharomyces cerevisiae were isolated and characterized from Debina must
      (Zitsa, Epirus, Greece). In addition, these strains were examined for their
      effect on the outcome of the wine fermentation process when used sequentially as
      starter cultures. The resulting wine, as analyzed over three consecutive years,
      was observed to possess a richer, more aromatic bouquet than wine from a
      commercial starter culture. These results emphasize the potential of employing
      indigenous yeast strains for the production of traditional wines with improved
      flavour.

PMID- 19859753
TI  - Production and optimization of cellulase-free, alkali-stable xylanase by Bacillus
      pumilus SV-85S in submerged fermentation.
AB  - This paper reports the production of a cellulase-free and alkali-stable xylanase
      in high titre from a newly isolated Bacillus pumilus SV-85S using cheap and
      easily available agro-residue wheat bran. Optimization of fermentation conditions
      enhanced the enzyme production to 2995.20 +/- 200.00 IU/ml, which was 9.91-fold
      higher than the activity under unoptimized basal medium (302.2 IU/ml).
      Statistical optimization using response-surface methodology was employed to
      obtain a cumulative effect of peptone, yeast extract, and potassium nitrate
      (KNO(3)) on enzyme production. A 2(3) central composite design best optimized the
      nitrogen source at the 0 level for peptone and yeast extract and at the -alpha
      level for KNO(3), along with 5.38-fold increase in xylanase activity. Addition of
      0.1% tween 80 to the medium increased production by 1.5-fold. Optimum pH for
      xylanase was 6.0. The enzyme was 100% stable over the pH range from 5 to 11 for 1
      h at 37 degrees C and it lost no activity, even after 3 h of incubation at pH 7,
      8, and 9. Optimum temperature for the enzyme was 50 degrees C, but the enzyme
      displayed 78% residual activity even at 65 degrees C. The enzyme retained 50%
      activity after an incubation of 1 h at 60 degrees C. Characteristics of B.
      pumilus SV-85S xylanase, including its cellulase-free nature, stability in alkali
      over a long duration, along with high-level production, are particularly suited
      to the paper and pulp industry.

PMID- 19859754
TI  - Structural-acoustic modal analysis of cylindrical shells: application to MRI
      scanner systems.
AB  - OBJECT: The acoustic noise in a magnetic resonance imaging (MRI) scanner bore is
      mainly introduced by the vibration of gradient coils. The interaction between
      acoustic modes in the scanner bore and structure modes in the coil structure
      leads to structural-acoustic coupling. In order to implement quiet MRI design,
      the structural-acoustic coupling mechanism in MRI machines needs to be fully
      investigated. MATERIALS AND METHOD: Structural analysis was first implemented
      using Love's classical shell theory. The concept of a "virtually closed cavity"
      was used in the acoustic modal analysis of the gradient coil duct. The dispersion
      curves and the number of modes per frequency band were used to reveal modal
      distribution properties for both structural modes and acoustic modes. Structural
      acoustic coupling modes were identified by superposition of the dispersion
      diagrams of the structural waves and acoustic waves. Experimental validation was
      implemented separately for the structural analysis and acoustic analysis.
      RESULTS: Independent structural modes and acoustic modes and their distribution
      patterns were calculated up to 3000Hz with various boundary conditions. Coupling
      modes were clearly revealed using the analysis procedures presented in this paper
      and were found to be in agreement with the ones identified from experimental
      measurements. CONCLUSION: These methods are effective for coupled and uncoupled
      modal analysis of MRI scanner systems and can be used for quiet MRI design or
      sound absorber design for existing MRI systems.

PMID- 19859755
TI  - Background shifts affect explanatory style: how a pragmatic theory of explanation
      accounts for background effects in the generation of explanations.
AB  - Cognitive scientists are interested in explanation because it provides a window
      into the cognition that underlies one's understanding of the world. We argue that
      the study of explanation has tended to focus on what makes an explanation "bona
      fide" as opposed to the processes involved in how the explanation is generated.
      In the current study, we asked participants to respond to the request for an
      explanation within a novel domain after we manipulated their initial exposure to
      the domain, and thus the background of the request. In two experiments, we found
      evidence that the background shaped participants' interpretations of the prompt
      for the explanation and that this, in turn, influenced whether they used a causal
      or functional style of explanation when responding to the prompt. We also asked
      participants to evaluate a number of explanations and found that the manipulation
      of the background did not have the same effect on the evaluative tasks. Our data
      support a pragmatic approach (e.g. The scientific image. Oxford University Press,
      Oxford, 1980) to the study of explanation generation, a philosophical approach
      which argues that the background influences the interpretation of the question,
      the development of a relevance relation which connects the question and
      explanation, and the identification of some set of candidate answers. We also
      suggest there is an important difference between the process of generating an
      explanation and evaluating an explanation, a difference that has escaped the
      attention of cognitive scientists thus far.

PMID- 19859757
TI  - n-3 PUFA as regulators of cardiac gene transcription: a new link between PPAR
      activation and fatty acid composition.
AB  - The fatty acids regulate gene expression directly binding to nuclear receptors or
      affecting the protein content of transcription factors. In this work,
      supplementing primary cultures of neonatal rat cardiomyocytes with 60 microM EPA
      or DHA, we demonstrated by an ELISA assay an increased PPAR beta/delta binding to
      DNA. n-3 PUFA supplementation deeply changed the acyl composition of both
      cytosolic and nuclear fractions. The high content of total fatty acids,
      particularly EPA and DHA, and its increase following supplementation suggested a
      selective accumulation of n-3 PUFAs in the nucleus, supporting the direct
      interaction of n-3 PUFA with PPAR. The activity of acyl-CoA thioesterase (ACOT),
      catalyzing the reaction leading to NEFA from acyl-CoA, increased in n-3 PUFA
      supplemented cells. The NEFA/acyl-CoA ratio is an important regulator of the
      fatty acid transport to the nucleus and consequent modulation of gene
      transcription, and although ACOT activity is not the only parameter of this
      ratio, it is important for the control of the NEFA pool composition. Our data
      further clarify what happens in cardiomyocytes following n-3 PUFA
      supplementation, linking the modification of acyl composition to ACOT activity
      and PPAR activation.

PMID- 19859761
TI  - Abstracts of the Irish Endocrine Society 34th Annual Meeting. November 6-7, 2009.
      Cork, Ireland.

PMID- 19859763
TI  - Aorto-right atrial tunnel: fetal heart failure, diagnosis, and treatment.
AB  - Aorto-right atrial tunnel (ARAT) is a rare clinical entity. Although it is a
      benign finding in most cases; it can present with significant right ventricular
      volume overload and congestive heart failure. This report describes the first
      fetal diagnosis of congenital aorto-right atrial tunnel and successful management
      of the heart failure by surgical intervention.

PMID- 19859762
TI  - N-terminal-pro-B-type natriuretic peptide in premature patent ductus arteriosus:
      a physiologic biomarker, but is it a clinical tool?
AB  - This study investigated whether N-terminal-pro-B-type natriuretic peptide (NT
      proBNP) levels could serve as prognostic indicators of the therapeutic
      responsiveness of the patent ductus arteriosus to pharmacologic treatment. The
      levels of NT-proBNP in premature neonates with hemodynamically significant
      patency of the ductus arteriosus (hsPDA) were assessed before and after treatment
      using ibuprofen, indomethacin, or both. The baseline NT-proBNP levels were
      similar in both the infants who responded and those who did not respond to
      medical treatment. The combined data for all the subjects showed that NT-ProBNP
      decreased after treatment, but the decrease did not correlate significantly with
      treatment success or failure. Of the 38 infants, 11 did not respond to treatment
      with ductal closure. Although the pretreatment NT-proBNP levels were similar, the
      posttreatment levels in the nonresponders remained significantly higher than in
      the responders. Moreover, in 3 (27%) of the 11 nonresponders, NT-proBNP actually
      increased rather than decreased with treatment. The NT-proBNP levels of seven
      infants increased over the course of the study. Within this group, however, the
      pretreatment NT-proBNP levels were significantly lower than in the overall
      population, with no differences in the posttreatment levels. Overall, the
      decrease in NT-proBNP with treatment, presented as the ratio of pretreatment-post
      treatment/pretreatment was not well correlated with the ductal therapeutic
      outcome. In summary, in the study population, NT-proBNP was not sufficiently
      sensitive for accurate prediction of ductal therapeutic responsiveness.

PMID- 19859764
TI  - Cardiac tumor in juvenile onset Behcet's disease: case report and review of the
      literature.
AB  - Behcet's disease is a chronic multisystemic inflammatory disorder characterized
      by orogenital ulcerations, uveitis, and occasional cardiac involvement. This
      report describes an atypical presentation of pediatric Behcet's disease with
      pulmonary emboli and a cardiac mass. A 16-year-old boy with a 2-year history of
      oral ulcers presented with weight loss, fever, joint pain, and a large tumor
      adhering to the free wall of the heart's right ventricle. Surgical biopsy
      demonstrated endomyocarditis with thrombus formation and led to the diagnosis. At
      the 2-year follow-up evaluation, intracardiac thrombus and pulmonic emboli had
      not recurred. Symptom control with immunosuppressive therapy was good.

PMID- 19859765
TI  - Lown-Ganong-Levine syndrome in a 3-month-old infant with isolated left
      ventricular noncompaction.
AB  - This report describes a 3-month-old boy with isolated left ventricular
      noncompaction admitted to a medical facility due to heart failure and
      dysrhythmia. His electrocardiogram showed a short PR interval and a normal QRS
      complex after abortion of supraventricular tachycardia in favor of Lown-Ganong
      Levine syndrome or enhanced atrioventricular nodal conduction.

PMID- 19859766
TI  - Anomalous origin of a coronary artery from the right branchiocephalic trunk
      associated with complex congenital heart disease.
AB  - This report describes the extremely rare case of a 42-day-old boy with anomalous
      origin of a single coronary artery from the right branchiocephalic trunk
      associated with hypoplastic left ventricle, mitral atresia, truncus arteriosus,
      total anomalous pulmonary venous drainage, and patent foramen ovale.

PMID- 19859767
TI  - Regression of a coronary arterial fistula in an infant with pulmonary atresia and
      an intact ventricular septum.
AB  - This report describes a premature newborn with pulmonary atresia and an intact
      ventricular septum who presented with a significant fistula between the right
      ventricle and the left anterior descending coronary artery (LAD). The right
      ventricle was not decompressed to prevent myocardial damage. After 2 months, the
      fistula had closed spontaneously. The pulmonary valve was opened, and
      biventricular circulation was achieved.

PMID- 19859768
TI  - Characteristics of coastal dune topography and vegetation in environments
      recently modified using beach fill and vegetation plantings, Veneto, Italy.
AB  - Human actions can contribute to degradation of coastal environments or they can
      increase the likelihood that these environments will be restored. Beach
      nourishment provides a basis for restoration, but ways must be found to add
      habitat improvement to projects designed for shore protection. This study
      examines how beach nourishment projects can help reinstate dune landscapes in
      locations where beaches and dunes had been replaced by static shore protection
      structures. Dune topography and vegetation on three nourished sites on the
      northern Adriatic Coast of Italy are compared to a reference site to evaluate
      changes after beach fill was emplaced. Results reveal how nourishment projects
      used for shore protection can restore the space available for dunes to form,
      increase the likelihood of sediment transfers inland and increase the diversity
      of topography and vegetation. Beach raking prevents formation and growth of
      hummocky, incipient backshore dunes that would otherwise evolve into a naturally
      functioning foredune. Sand-trapping fences can speed the process of foredune
      development but can be counterproductive if they interfere with transport to
      beach grass (Ammophila littoralis) planted landward of them. Shore protection
      structures can provide stability and more time for dune evolution on eroding
      shores, resulting in greater species richness and longer retention of ecological
      niches. These structures need not be required if re-nourishment occurs frequently
      enough to provide a beach wide enough to protect against storm wave uprush.

PMID- 19859769
TI  - Predictive factors of response to decongestive therapy in patients with breast
      cancer-related lymphedema.
AB  - BACKGROUND: Many studies have reported the benefits of Decongestive treatment in
      patients with breast-cancer-related lymphedema (BCRL) but few have study what are
      the predictive factors of response. METHODS: We performed a prospective,
      multicenter controlled cohort study of 171 patients with BCRL to identify
      independent predictive factors of response to decongestive treatment (CDT).
      Demographic data and clinical and lymphedema characteristics were collected
      prospectively. The end point was the "percentage reduction in excess volume
      (PREV)." Volumes were measured prior and at the end of CDT. Factors associated
      with response (PREV) were tested in univariate and multivariate analyses using
      linear regression techniques. RESULTS: Median age was 60.4 years (range 32-84);
      mean lymphedema chronicity 4 years [95% confidence interval (95% CI): 3.1-5.0];
      mean baseline excess volume (EV) was 936 mL (95% CI: 846-1026), and mean
      percentage EV was 35.3% (95% CI: 32.0-38.7); compliance to bandages was good in
      81.3% of patients. PREV was 71.7% (95% CI: 65.2-78.2). After univariate
      screening, 11 variables were found to be associated with PREV but only 4
      variables were independent predictive factors of response to CDT in the
      multivariate analysis: Venous insufficiency, percentage of EV (the higher the EV,
      the lower the reduction with CDT); compliance to bandages (a good compliance
      improved PREV in 25%), and treatment in autumn (better results than during the
      rest of the year). CONCLUSIONS: This study shows that compliance to bandages
      during CDT is one of the most important predictors of response. Moreover, data
      support the idea that more severe lymphedemas have a worse response to treatment,
      and it should be recommended in early stages. The association between the season
      of treatment and response was also very strong, so weather conditions are an
      additional factor that must be taken into account in further studies.

PMID- 19859770
TI  - Hypoxic single-pass isolated hepatic perfusion of hypotonic Cisplatin: safety
      study in the pig.
AB  - BACKGROUND: Isolated hepatic perfusion (IHP) of chemotherapy has been proposed to
      deliver high doses of drug while avoiding systemic toxicity. Hypotonic cisplatin
      has a high in vitro activity on human colon cancer cells. We studied the safety
      of a 30-min hypoxic single-pass IHP with hypotonic cisplatin. METHODS: A
      preliminary in vitro assay was performed to compare the cytotoxicity of cisplatin
      and oxaliplatin, in either a normotonic or hypotonic medium. Cisplatin in
      hypotonic medium was then chosen for the in vivo IHP. Eleven pigs underwent 30
      min of IHP with 0, 50, 75, or 100 mg/L of cisplatin in a hypotonic solution under
      total vascular exclusion of the liver. Clinical and biological parameters were
      recorded for 30 days, and liver histology was performed at necropsy. The
      cytotoxic activity of the effluent against resistant human colon cancer cells was
      tested in vitro. RESULTS: No hepatic failure was recorded after IHP with
      cisplatin, but limited foci of necrosis were found at necropsy in animals
      receiving 75 or 100 mg/L of cisplatin. No clinical, biological, macroscopic, or
      microscopic toxicity was observed after IHP with 50 mg/L of hypotonic cisplatin.
      The liver effluent showed high in vitro cytotoxic activity against colon cancer
      cells. CONCLUSIONS: A hypoxic single-pass isolated liver perfusion with hypotonic
      cisplatin is feasible and safe. Effluent from the liver is highly cytotoxic on
      cancer cells. A clinical study with 50 mg/L of hypotonic cisplatin is warranted
      in patients with unresectable liver metastases from colon cancer.

PMID- 19859771
TI  - Temporary placement of self-expanding oesophageal stents as bridging for neo
      adjuvant therapy.
AB  - BACKGROUND: Placement of self-expanding stents is an effective palliation for
      dysphagia in non-resectable oesophageal or proximal gastric cancer. The aim of
      this analysis was to assess the efficacy of temporary stent placement for
      dysphagia relief during neo-adjuvant treatment for locally advanced disease.
      METHODS: A total of 38 patients scheduled for neo-adjuvant chemo(radio)therapy
      for locally advanced oesophageal cancer (n = 29), cardia cancer (n = 8) or
      subcardial gastric cancer (n = 1) underwent placement of self-expanding plastic
      stents (n = 13) or covered metal stents (n = 25) due to severe dysphagia and
      weight loss. RESULTS: Instant dysphagia relief was achieved in 37 (97.4%) of 38
      patients. Dysphagia scores declined from mean 3.0 +/- 0.7 before stent placement
      to 0.6 +/- 0.9 at restaging. After completion of the neo-adjuvant therapy 20
      (52.6%) of the 38 patients underwent resection of the tumour, 5 patients (13.2%)
      underwent primary resection without receiving chemotherapy while 12 patients
      (31.6%) did not undergo surgery. Stent-related complications were observed as
      perforation (n = 1), mediastinitis (n = 1), tracheo-oesophageal fistula (n = 2),
      bleeding (n = 1) and jejunal perforation caused by a migrated stent (n = 1).
      Serum albumin significantly decreased in patients with progressive disease
      despite successful stenting (40.0 +/- 4.9 mg/dl versus 29.7 +/- 6.4 mg/dl, p <
      0.05) while stable albumin levels were found in patients who underwent surgery
      (39.9 +/- 4.3 mg/dl versus 39.1 +/- 3.8 mg/dl, p = 0.484). CONCLUSION: Placement
      of self-expanding stents is highly effective for instant dysphagia relief,
      enabling adequate oral nutrition during neo-adjuvant therapy, but is limited by a
      high re-intervention rate.

PMID- 19859772
TI  - Isolated diaphyseal fractures of the radius in skeletally immature patients.
AB  - Diaphyseal radius fractures without associated ulna fracture or radioulnar
      dislocation (isolated fracture of the radius) are recognized in adults but are
      rarely described in skeletally immature patients. A search of our database (1974
      2002) identified 17 pediatric patients that had an isolated fracture of the
      radius. Among the 13 patients with at least 1 year follow-up, ten were treated
      with manipulative reduction and immobilization in an above elbow cast and three
      had initial operative treatment with plate and screw fixation. These 13 patients
      were evaluated for an average of 18 months (range, 12 to 45 months) after injury
      using the system of Price and colleagues. The incidence of isolated diaphyseal
      radius fractures in skeletally immature patients was 0.56 per year in our
      database and represented 27% of the 63 patients with a diaphyseal forearm
      fracture. All 13 patients, with at least 1 year follow-up, regained full elbow
      flexion and extension and full forearm rotation. According to the classification
      system of Price, all 13 patients (100%) had an excellent result. As in adults,
      isolated radius fractures seem to occur in children more frequently than
      previously appreciated. Treatment of isolated radius fractures in skeletally
      immature patients has a low complication rate, and excellent functional outcomes
      are the rule.

PMID- 19859773
TI  - Cerebellar disorders--at the crossroad of molecular pathways and diagnosis.
AB  - Our understanding of the pathogenesis of cerebellar ataxias has started several
      decades ago and is continuously growing. The numerous mechanisms of cerebellar
      dysfunction are being discovered by numerous groups of researchers worldwide.
      Neuronal damage results from a complex interaction of metabolic pathways, which
      leads to symptoms observed in cerebellar disorders. The main mechanisms at the
      molecular level are the following: impairment of DNA repair and replication,
      deregulation of transcription/deficits of processing/transport of RNA, abnormal
      protein transport and misfolding, aggregates both at the nuclear and cytosolic
      level, activation of caspases, apoptosis, involvement of autophagic mechanisms,
      oxidative stress and mitochondrial dysfunction, excitotoxicity, abnormal lipid
      metabolism, impaired axonal transport and vesicle trafficking, and defects of the
      neurotransmission. The convergence of the current clinical classification with
      molecular findings is expected. This integration is a basic substrate for the
      rationale development of therapies.

PMID- 19859775
TI  - Ultrasound assessment of the vertebral level of the palpated intercristal
      (Tuffier's) line.
AB  - PURPOSE: Identification of a particular vertebral level by clinical landmark
      palpation is inaccurate. This study uses ultrasound imaging to assess the
      vertebral level at which the palpated intercristal line occurs in subjects
      clinically positioned to receive a neuraxial technique. METHODS: Following
      Research Ethics Board approval and informed written consent, 114 adult subjects
      were seated in the position used clinically for placement of a neuraxial block. A
      single investigator marked the skin where the palpated intercristal line crossed
      the spinous processes. A 2-5 MHz curved ultrasound probe in paramedian
      orientation was advanced cephalad from the sacrum, counting the ultrasound
      visualized intervertebral levels until the skin marking was encountered. The
      weight, height, waist circumference, body mass index, and age of the volunteers
      were recorded. These physical characteristics and relationship to the ultrasound
      measured palpated intercristal line were assessed using the Chi square and Tukey
      Honestly Statistically Different tests. RESULTS: Using ultrasound, the palpated
      intercristal line was identified at the L3-4 interspace in 83 (73%), at L4-5 in
      16 (14%), and at L2-3 in 15 (13%) of volunteers, respectively. Those with a
      palpated intercristal line at L2-3 were taller (mean difference 7.8 cm, 95%
      confidence interval 2.6-13.0 cm) and more likely to be male (22% vs 6%; P =
      0.016) than those imaged with a palpated intercristal line at L3-4 or below.
      CONCLUSIONS: According to ultrasound, the palpated intercristal line falls at the
      L3-4 interspace, or below, in the majority of subjects positioned for neuraxial
      block in the sitting position. A palpated intercristal line at L2-3 was more
      likely in tall and male individuals.

PMID- 19859776
TI  - Preload or coload for spinal anesthesia for elective Cesarean delivery: a meta
      analysis.
AB  - BACKGROUND: Hypotension following spinal anesthesia for Cesarean delivery is
      common. Fluid loading is recommended to prevent hypotension, but preload is often
      ineffective. In non-pregnant patients, coloading has been shown to better
      maintain cardiac output after spinal anesthesia. The purpose of this meta
      analysis was to determine whether the timing of the fluid infusion, before
      (preload) or during (coload) induction of spinal anesthesia for Cesarean
      delivery, influences the incidence of maternal hypotension or neonatal outcome.
      METHODS: We retrieved randomized controlled trials that compared a fluid preload
      with coload in patients undergoing spinal anesthesia for elective Cesarean
      delivery. We graded the articles for quality of reporting (maximum score = 5) and
      recorded the incidence of hypotension, lowest blood pressure, the incidence of
      maternal nausea and vomiting, umbilical cord pH, and Apgar scores. We combined
      the results using random effects modelling. RESULTS: We retrieved eight studies
      comprised of 518 patients. The median quality score for the published studies was
      three. The incidence of hypotension in the coload group was 159/268 (59.3%)
      compared with 156/250 (62.4%) in the preload group (odds ratio [OR] = 0.93; 95%
      confidence interval [CI] 0.54-1.6). There were no significant differences between
      groups in any of the other outcomes. CONCLUSIONS: It is unnecessary to delay
      surgery in order to deliver a preload of fluid. Regardless of the fluid loading
      strategy, the incidence of maternal hypotension is high. Prophylactic or
      therapeutic vasopressors may be required in a significant proportion of patients.

PMID- 19859774
TI  - Cerebellar lingula size and experiential risk factors associated with high levels
      of alcohol and drug use in young adults.
AB  - Previous studies have reported cerebellar abnormalities or static ataxia
      associated with risk for chronic use of alcohol and drugs. Adverse childhood
      experience is another strong risk factor for later substance abuse. We therefore
      sought to ascertain the relationship between morphological phenotypes of the
      lingula (lobule I) of the anterior cerebellar vermis, and exposure to emotional
      (EM) versus physical (PM) maltreatment, on the degree of ongoing alcohol or drug
      use. The study design consisted of a cross-sectional in vivo neuroimaging study,
      utilizing retrospective assessment of maltreatment history and self-reports of
      alcohol and substance use. Study participants were 153 subjects (54 M/99F, 21.9
      +/- 2.2 years) selected for imaging from a database of 1,402 community
      participants 18-25 years of age, who completed a detailed online screening
      instrument and met rigorous inclusion/exclusion criteria. Subjects were exposed
      to only physical abuse or harsh corporal punishment (HCP; PM group, n = 37) and
      parental verbal abuse and/or witnessing domestic violence (EM group, n = 58) or
      had no history of maltreatment or axis I disorders (n = 58). The main outcome
      measures consisted of the gray matter volume of lobule I as measured by manual
      tracing, number and type of alcoholic beverages consumed during a drinking
      session, number of sessions per month, and monthly drug use, along with family
      history of drug and alcohol abuse. Lingula thickness was not attenuated by
      alcohol use or maltreatment history. However, increased lingula thickness was
      associated with greater consumption of drugs and hard liquor, particularly in
      physically maltreated subjects who consumed 2.5- and 2.7-fold more alcohol and
      used drugs 6.1- and 7.8-fold more frequently than controls or EM subjects,
      respectively. In conclusion, physical maltreatment was observed to interact with
      cerebellar morphology resulting in a strong association with alcohol and
      substance use. Lingula thickness may represent a novel, experientially sensitive,
      phenotypic risk factor for enhanced alcohol and drug use that perhaps modulates
      sensitivity to these agents.

PMID- 19859778
TI  - Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial
      infarction: a mechanism contributing to myocardial remodeling?
AB  - Ventricular remodeling following myocardial infarction (MI) includes myocardial
      hypertrophy, a process requiring increased protein synthesis and sarcomere
      assembly. The anti-hypertrophic effect of MuRF1/MafBx, both muscle-specific E3
      ubiquitin ligases, has been demonstrated in animal experiments and in cultured
      cardiomyocytes. We assessed MuRF1/MAFbx expression in myocardium remote of
      recently (<2 weeks) infarcted regions (MI), compared with patients undergoing
      coronary artery bypass surgery, with normal systolic function and without
      previous infarction (control or Con). Left ventricular myocardial biopsies were
      obtained from the contralateral normal zone in MI (n = 14) patients and from the
      Con (n = 12) group. MuRF-1/MAFbx expression was assessed using RT-PCR and Western
      blot (WB). In addition, the myocardial expression of TNF-alpha was measured (RT
      PCR) and troponin I, beta-myosin and phosphorylated Akt/Akt (pAkt/Akt) were
      quantified (WB). MuRF1 and MAFbx expression (mRNA and protein level) were
      significantly reduced in biopsies from MI patients. TNF-alpha was significantly
      higher in MI and exhibited a negative correlation with MuRF1 and MAFbx. The
      expression of troponin I and cardiomyocyte size were increased in MI in
      comparison to Con, whereas beta-myosin expression was not altered. When compared
      with Con, pAkt/Akt was elevated. The results of the present study suggest that
      the atrogenes MuRF1/MAFbx are involved in regulating the hypertrophic response,
      characteristic of the early post-infarction remodeling phase. Reduced expression
      of MuRF1 and MAFbx in the myocardium might permit hypertrophy, which is supported
      by the elevation of troponin I. A regulatory role of TNF-alpha needs to be
      confirmed in further experiments.

PMID- 19859779
TI  - Anomalous head of the brachial muscle penetrates the deltoid muscle.
AB  - We report here, for the first time a specimen in which the insertion of the
      deltoid muscle is divided into two parts, composing a canal. The brachial muscle
      was composed of medial, lateral, and anomalous heads. The anomalous head arose as
      a thin tendon from the surgical neck of humerus, passed through the canal, and
      then became confluent with the lateral head. The musculocutaneous nerve
      innervated the brachial muscle. The lateral head, but not the anomalous head,
      received a thin branch from the radial nerve.

PMID- 19859780
TI  - Persistent hypoglossal artery with hypoplasia of the vertebral and posterior
      communicating arteries.
AB  - We observed a rare case of the right persistent hypoglossal artery (PHA) in the
      posterior cranial fossa of a deceased 74-year-old Japanese man who did not have
      any clinical manifestations related to this anomaly when alive. The large-sized
      PHA originating from the cervical internal carotid artery passed through the
      hypoglossal canal together with the hypoglossal nerve and reached the posterior
      cranial fossa to anastomose the basilar artery. In addition, the ipsilateral
      vertebral artery and bilateral posterior communicating arteries were hypoplastic.
      Here, we discuss the developmental mechanisms underlying the formation of the PHA
      and the spectrum of diseases related to its presence.

PMID- 19859781
TI  - Vitamin E supplementation decreases muscular and oxidative damage but not
      inflammatory response induced by eccentric contraction.
AB  - The purpose of this study was to investigate the effects of vitamin E
      supplementation on muscular and oxidative damage, as well as the inflammatory
      response induced by eccentric exercise (EE) in humans. Twenty-one participants
      with a mean age of 22.5 +/- 4 years, weight of 68.2 +/- 4.9 kg, and height of 173
      +/- 4.3 cm were selected and divided randomly into two groups: supplemented (S)
      (n = 11) and placebo (P) (n = 10). Fourteen days after starting supplementation,
      subjects performed EE (three sets until exhaustion with elbow flexion and
      extension on the Scott bench, 80% 1 RM). Blood samples were collected on days 0,
      2, 4, and 7 after EE. Muscle soreness (MS), lactate dehydrogenase (LDH) activity,
      lipid peroxidation, protein carbonylation, tumor necrosis factor-alpha (TNF
      alpha), and interleukin 10 (IL-10) levels were determined. We measured a
      significant increase in MS, LDH, lipid peroxidation, and carbonylation in both
      groups on days 2, 4, and 7 after eccentric contractions (EC). Values of the
      supplement group were lower than those of the placebo group at 4 and 7 days after
      EC in all parameters. Both groups showed significantly increased TNF-alpha on the
      second day and IL-10 concentration on the fourth and seventh days after EE. The
      results suggest that vitamin E supplementation represents an important factor in
      the defense against oxidative stress and muscle damage but not against the
      inflammatory response in humans.

PMID- 19859782
TI  - Cognitive effects of high-frequency repetitive transcranial magnetic stimulation:
      a systematic review.
AB  - Transcranial magnetic stimulation (TMS) was introduced as a non-invasive tool for
      the investigation of the motor cortex. The repetitive application (rTMS), causing
      longer lasting effects, was used to study the influence on a variety of cerebral
      functions. High-frequency (>1 Hz) rTMS is known to depolarize neurons under the
      stimulating coil and to indirectly affect areas being connected and related to
      emotion and behavior. Researchers found selective cognitive improvement after
      high-frequency (HF) stimulation specifically over the left dorsolateral
      prefrontal cortex (DLPFC). This article provides a systematic review of HF-rTMS
      studies (1999-2009) stimulating over the prefrontal cortex of patients suffering
      from psychiatric/neurological diseases or healthy volunteers, where the effects
      on cognitive functions were measured. The cognitive effect was analyzed with
      regard to the impact of clinical status (patients/healthy volunteers) and
      stimulation type (verum/sham). RTMS at 10, 15 or 20 Hz, applied over the left
      DLPFC, within a range of 10-15 successive sessions and an individual motor
      threshold of 80-110%, is most likely to cause significant cognitive improvement.
      In comparison, patients tend to reach a greater improvement than healthy
      participants. Limitations concern the absence of healthy groups in clinical
      studies and partly the absence of sham groups. Thus, future investigations are
      needed to assess cognitive rTMS effects in different psychiatric disorders versus
      healthy subjects using an extended standardized neuropsychological test battery.
      Since the pathophysiological and neurobiological basis of cognitive improvement
      with rTMS remains unclear, additional studies including genetics, experimental
      neurophysiology and functional brain imaging are necessary to explore stimulation
      related functional changes in the brain.

PMID- 19859785
TI  - Genetic stability and linkage analysis of the 2009 Influenza A(H1N1) virus based
      on sequence homology.
AB  - The 2009 swine-origin Influenza A virus subtype H1N1 (S-OIV) is generally
      believed to be a mixture of human, bird and swine viruses, resulting from
      multiple reassortments. The evolutionary origin of the S-OIV is of high interest
      but still remains obscure. In order to understand the evolution of the new virus,
      we performed sequence homology, segment stability and segment linkage analysis,
      as well as analysis of the host and geographic distribution of the evolutionarily
      related viruses. Stability analysis demonstrated that segment 6 (NA) was the most
      unstable one, followed by segment 4 (HA), while the other 6 segments were
      relatively stable. Host and geographic distribution analysis indicated that all 8
      segments of the new virus were closely related to those of swine influenza
      viruses circulating either in North America or in Eurasia. Segment linkage
      analysis showed that segments 1 (PB2), 2 (PB1), 3 (PA), 4 (HA), 5 (NP), and 8
      (NS) are in linkage disequilibrium exclusively with North American swine
      influenza viruses, and segments 6 (NA) and 7 (M) are evolutionarily linked solely
      with Eurasian swine influenza viruses. Two North American swine strains and 2
      Eurasian swine strains were identified as possible ancestors of S-OIV 2009. Based
      on the most recent linkage analysis with the updated influenza sequences, South
      Dakota avian strains were found to be the closest known relatives of S-OIV 2009.

PMID- 19859787
TI  - Reliability and validity of the Dutch version of the maternal antenatal
      attachment scale.
AB  - In this study, we investigated the psychometric qualities of the Dutch version of
      the Maternal Antenatal Attachment Scale (MAAS). In a monocentric prospective
      observational cohort study, 403 expectant mothers completed a booklet with
      questionnaires in the first (T1), second (T2), and third (T3) pregnancy
      trimesters. In addition to the MAAS (T1-T3), the following measures were used:
      the Marlowe-Crowne Social Desirability Scale (T1), the Parental Bonding Inventory
      (T1), the Relationship Questionnaire (T1) the Facilitator scale and the Regulator
      scale (T3), the Edinburgh Postnatal Depression Scale (T1-T3) and the Pregnancy
      Related Anxiety Questionnaire (T1-T3). In this study, the mean of the MAAS scales
      increased as the pregnancy progressed. Good internal reliabilities were found for
      the Total MAAS scale, the Quality subscale and the Preoccupation subscale. Small
      to-moderate correlations were found with social desirability, maternal
      orientation, parental care and adult attachment. Maternal mood was weakly
      associated with the quality but not with the intensity of the maternal attachment
      feelings. Overall, our findings suggest that the Dutch version of the Maternal
      Antenatal Attachment Scale is a reliable and valid measure of the early emotional
      tie between a pregnant woman and her unborn child.

PMID- 19859786
TI  - Ultrastructural and biochemical investigations of protein mobilization of Mucuna
      pruriens (L.) DC. cotyledons and embryo axis.
AB  - The mobilization of storage reserves, with particular emphasis on storage
      proteins of Mucuna pruriens (L.) DC., cotyledons, and embryo was investigated
      from the ultrastructural and biochemical points of view. Proteins and starch were
      the two main storage substances in cotyledons, and proteins and lipids were the
      main ones in the embryo. Embryo protein bodies were smaller and fewer in number
      than those of cotyledons. Structural and ultrastructural data determined between
      24 and 48 h after imbibition and between 48 and 72 h after imbibition, the end of
      significant embryo and cotyledon protein mobilization, respectively, indicating
      more precocious storage protein mobilization in the axis than cotyledons.
      Moreover, storage protein mobilization in embryo and cotyledons occurred before
      the end of germination. Water soluble proteins were separated by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis, producing 29 bands with molecular
      weights from 14 to 90 KDa. Embryo extract contained more proteins than cotyledon
      extract, contained seven characteristic bands, and showed a higher variability of
      the optical density trend than cotyledon.

PMID- 19859788
TI  - An open trial with cognitive behavioral therapy for blood- and injection phobia
      in pregnant women-a group intervention program.
AB  - Around 7% of pregnant women suffer from blood- and injection phobia. The aim was
      to investigate if cognitive behavior group therapy (CBT) is effective in treating
      pregnant women's blood- and injection phobia. Thirty pregnant women with blood-
      and injection phobia according to DSM-IV took part in an open treatment
      intervention. A two-session cognitive behavior group therapy was conducted. As
      controls, 46 pregnant women with untreated blood- and injection phobia and 70
      healthy pregnant women were used. Repeated measures ANOVA were performed. The
      scores for the CBT treatment group on the "Injection Phobia Scale-Anxiety" were
      reduced both after each treatment session and postpartum (p < 0.001). Anxiety and
      depressive symptoms were also reduced (p < 0.001). Cognitive-behavior group
      therapy for pregnant women with blood- and injection phobia is effective and
      stable up to at least 3 months postpartum. It seems also to reduce anxiety and
      depressive symptoms during pregnancy.

PMID- 19859790
TI  - c-Jun-NH2 terminal kinase (JNK)-mediates AP-1 activation by thioredoxin:
      phosphorylation of cJun, JunB, and Fra-1.
AB  - Thioredoxin (Trx) is a small ubiquitous protein, which has been shown to be
      involved in redox-dependent cellular functions. In this article, we demonstrate
      that the increased level of Trx induces AP-1 DNA binding in a redox-dependent
      manner by activating JNK subgroup of MAPKs. The majority of AP-1 DNA binding
      complex was found to be composed of cJun, JunB, and Fra-1. Increased expression
      of Trx resulted in phosphorylation of cJun, Jun B, and Fra-1. Further, increased
      expression of Trx induced the phosphorylation of MKK4 and MKK7 which are upstream
      kinases of the JNK signaling cascade. In co-transfection studies, AP-1-dependent
      luciferase reporter vector and pcDNA3-Trx increased luciferase activity
      demonstrating that increased expression of Trx increases AP-1 transactivation. In
      addition, dominant-negative JNK kinase (dnJNK/MKK4) or dominant-negative JNK
      (dnJNK) inhibited Trx-mediated AP-1 transactivation, as well as AP-1 DNA binding.
      Furthermore, transfection of kinase-dead MEKK1, an initiating kinase of the JNK
      pathway inhibited Trx-mediated AP-1 transactivation and DNA binding, suggesting
      that MEKK1 may mediate Trx-induced AP-1 activation. In contrast, wild-type MEKK1
      overexpression did not inhibit Trx-mediated AP-1 activation. Taken together, our
      data demonstrate that increased expression of Trx induces MKK4/MKK7-dependent JNK
      activation, resulting in enhanced DNA binding, and transactivation of AP-1
      transcription factor.

PMID- 19859791
TI  - A novel gastro-retentive osmotic pump capsule using asymmetric membrane
      technology: in vitro and in vivo evaluation.
AB  - PURPOSE: The purpose of this paper is to develop a novel gastro-retentive osmotic
      pump capsule using asymmetric membrane technology. METHODS: The physical
      characteristics of capsule walls and drug delivery behaviors of the system were
      compared through different coating solutions. The formulation with the glycerin
      and diethyl phthalate ratio of 5:4 appears to be the best. The thickness of
      asymmetric membranes was evaluated by withdrawing speed. The relation between the
      two can be fitted to a linear model. The floating abilities were investigated
      through filling polyethylene oxide of different molecular weight into the
      capsules. WSR N-80 (molecular weight 200000) is chosen for the longest floating
      time. Central composite design-response surface methodology was used to
      investigate the influence of factors on the responses. The in vivo
      pharmacokinetics were studied in beagle dogs. RESULTS AND CONCLUSIONS: A second
      order polynomial equation was fitted to the data, and the actual response values
      are in good accordance with the predicted ones. The optimized formulation
      displays a complete drug delivery, zero-order release rate and 12 h floating
      time. The in vivo study results clearly indicate the controlled and sustained
      release of Famotidine from the system, and the relative bioavailability of this
      preparation is about 1.605 in comparison to that of the marketed preparation.

PMID- 19859789
TI  - Use of pifithrin to inhibit p53-mediated signalling of TNF in dystrophic muscles
      of mdx mice.
AB  - Tumour Necrosis Factor (TNF) plays a major role in exacerbating necrosis of
      dystrophic muscle; however, the precise molecular mechanism underlying this
      effect of TNF is unknown. This study investigates the role that p53 plays in TNF
      mediated necrosis of dystrophic myofibres by inhibiting p53 using pifithrin-alpha
      and three pifithrin-beta analogues. Tissue culture studies using C2C12 myoblasts
      established that pifithrin-alpha was toxic to differentiating myoblasts at
      concentrations greater than 10 muM. While non-toxic concentrations of pifithrin
      alpha did not prevent the TNF-mediated inhibition of myoblast differentiation,
      Western blots indicated that nuclear levels of p53 were higher in TNF-treated
      myoblasts indicating that TNF does elevate p53. In contrast, in vivo studies in
      adult mdx mice showed that pifithrin-alpha significantly reduced myofibre
      necrosis that resulted from voluntary wheel running over 48 h. These results
      support the hypothesis that p53 plays some role in TNF-mediated necrosis of
      dystrophic muscle and present a potential new target for therapeutic
      interventions.

PMID- 19859792
TI  - Why hypothetical protein KPN00728 of Klebsiella pneumoniae should be classified
      as chain C of succinate dehydrogenase?
AB  - Twenty percent of genes that encode for hypothetical proteins from Klebsiella
      pneumoniae MGH78578 were identified, leading to KPN00728 and KPN00729 after
      bioinformatics analysis. Both open reading frames showed high sequence homology
      to Succinate dehydrogenase Chain C (SdhC) and D (SdhD) from Escherichia coli.
      Recently, KPN00729 was assigned as SdhD. KPN00728 thus remains of particular
      interest as no annotated genes from the complete genome sequence encode for SdhC.
      We discovered KPN00728 has a missing region with conserved residues important for
      ubiquinone (UQ) and heme group binding. Structure and function prediction of
      KPN00728 coupled with secondary structure analysis and transmembrane topology
      showed KPN00728 adopts SDH-(subunit C)-like structure. To further probe its
      functionality, UQ was docked on the built model (consisting KPN00728 and
      KPN00729) and formation of hydrogen bonds between UQ and Ser27, Arg31 (KPN00728)
      and Tyr84 (KPN00729) further reinforces and supports that KPN00728 is indeed SDH.
      This is the first report on the structural and function prediction of KPN00728 of
      K. pneumoniae MGH78578 as SdhC.

PMID- 19859793
TI  - The role of family obligations and school adjustment in explaining the immigrant
      paradox.
AB  - This study examined the role of family obligations and school adjustment in
      explaining immigrant adolescents' adaptation. Despite a relatively low socio
      economic status, immigrant adolescents have been found to have a pattern of
      adaptation superior to that of national adolescents. Immigrant adolescents'
      strong sense of family obligations and positive school adjustment have been used
      to explain these positive adaptation outcomes. Using self-reports in a sample of
      277 national adolescents (45.5% female) and a sample of 175 non-western immigrant
      adolescents (58.9% female), both samples with a mean age of 15 years, it was
      found that despite a lower socio-economic status, the adaptation of immigrant
      adolescents was as good as the nationals' adaptation. Immigrant adolescents
      scored higher on family obligations and school adjustment. Family obligations and
      school adjustment were found positively related to adaptation outcomes in the
      national and the immigrant adolescent sample. Findings suggest that, in
      underprivileged environments, a strong sense of family obligations may help
      immigrants as well as national adolescents achieve a positive pattern of
      adaptation.

PMID- 19859794
TI  - Benefits and difficulties in measuring HDL subfractions and human paraoxonase-1
      activity during statin treatment.
AB  - Dyslipidaemia including decreased high density lipoprotein cholesterol
      concentration is one of several factors that have been implicated in increased
      cardiovascular risk. Since their introduction in the 1980s, 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have emerged
      as the one of the best-selling class of medications to date, with numerous trials
      demonstrating powerful efficacy in preventing cardiovascular diseases. Although
      statins have been shown to modestly raise or not alter HDL-cholesterol, their
      effect on HDL subfractions and on HDL-associated enzymes including human
      paraoxonase-1 (PON1) has not yet been fully explored. This review summarizes the
      currently available data on the effect of statins on HDL subfractions and on PON1
      activity with a particular emphasis on the clinical relevance of these effects.
      Moreover, methodological problems of HDL subfraction and PON1 activity
      determinations are also discussed.

PMID- 19859795
TI  - Stimulus characteristics affect humor processing in individuals with Asperger
      syndrome.
AB  - The present paper aims to investigate whether individuals with Asperger syndrome
      (AS) show global humor processing deficits or whether humor comprehension and
      appreciation depends on stimulus characteristics. Non-verbal visual puns,
      semantic and Theory of Mind cartoons were rated on comprehension, funniness and
      the punchlines were explained. AS individuals did not differ to the control group
      in humor appreciation of visual puns. However, they had difficulty understanding
      and appreciating Theory of Mind cartoons and provided mentalistic explanations
      less frequently than controls suggesting that humor processing is strongly
      related to the cognitive requirements that the stimuli pose on the perceiver.
      Furthermore, AS individuals referred in all conditions more frequently to non
      joke relevant details. Therefore, humor processing is also influenced by their
      detail-oriented processing style.

PMID- 19859798
TI  - Doing gender in sex and sex research.
AB  - Gender is central to sexuality, and vice versa, but there are a number of
      difficulties with the treatment of gender in sex research. Apparently, it is hard
      to find a balance between two conflicting needs. First, obviously, it is
      necessary to make distinctions between women and men, for political as well as
      research-technical and theoretical reasons. A second requirement, at odds with
      the first one, is the necessity to understand gender and its relation to
      sexuality and the body as much more complex than simplistically referring to two
      sets of individuals. This is all the more necessary when one realizes the
      possible drawbacks of exaggerating the differences between the sexes (in
      particular when they are biologically explained), because of stereotyping,
      stigmatizing, and expectancy confirmatory processes. This essay identifies and
      discusses 10 difficulties in the treatment of gender in sex research, reflects on
      their origins, and reviews theory and evidence with the aim to (1) consider the
      relative strength of gender/sex as an explanatory variable compared to other
      factors and processes explaining differences between men and women on a number of
      sexual aspects, (2) inform an understanding of gender and its relation to
      sexuality as an ongoing, open-ended, multi-determined, situated, interactional
      process, with the body as a third player, and (3) argue in favor of a nuanced,
      well-balanced treatment of gender in sex research.

PMID- 19859796
TI  - Sulfasalazine induces apoptosis of HBx-expressing cells in an NF-kappaB
      independent manner.
AB  - The Hepatitis B virus (HBV) is a causative agent of acute chronic hepatitis,
      cirrhosis, and hepatocarcinoma. The Hepatitis B virus X protein (HBx) has
      pleiotypic functions in the regulation of proliferation and apoptosis. It has
      been suggested that the anti-inflammatory drug sulfasalazine, which is commonly
      used to treat rheumatoid arthritis and inflammatory bowel disease, inhibits
      nuclear factor NF-kappaB and induces cell death in HBx-expressing liver cells. In
      this study, we demonstrate that sulfasalazine induces cell death via apoptosis in
      HBx-expressing liver cells, as evidenced by characteristic changes in nuclear
      morphology, cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3 and
      caspase-9, and activation of caspase-3. We also demonstrate that inhibition of NF
      kappaB by siRNA fails to induce apoptosis of HBx-expressing liver cells,
      indicating that sulfasalazine modulates apoptosis of HBx-expressing cells in an
      NF-kappaB-independent manner.

PMID- 19859797
TI  - Transgenic expression of tomato bushy stunt virus silencing suppressor P19 via
      the pOp/LhG4 transactivation system induces viral-like symptoms in tomato.
AB  - During natural infection, the Tomato bushy stunt virus (TBSV) silencing
      suppressor protein P19 is expressed at high levels, which are required for
      optimum viral pathogenicity and silencing suppression. To date, expression of P19
      in transgenic host plants has failed to achieve comparable expression levels and
      thus has provided only limited information on its in planta effects. To obtain
      high P19 expression and study its effects on host plant development in the
      absence of virus infection, we generated HA-tagged P19 (P19HA)-transgenic tomato
      reporter plants using the pOp/LhG4 transactivation system, which separates
      transformation from transgene expression. Upon reporter plant activation with a
      strong constitutive promoter, the transactivated F1 plants expressed high levels
      of a functional P19HA protein and displayed multiple abnormal phenotypes, some of
      which were highly reminiscent of the symptoms described previously for TBSV
      infected tomato. Moreover, phenotype severity correlated with P19HA expression
      level, amount of bound miRNA/miRNA* duplexes, and accumulation of miRNA target
      transcripts. Together our results demonstrate that the tomato miRNA pathway is
      markedly compromised by P19, in particular when this protein is relatively
      abundant, as occurs during natural infection. We suggest that such interference
      with endogenous silencing may be responsible for at least some of the symptoms
      characteristic of TBSV-infected tomato.

PMID- 19859799
TI  - Validation of the sexual excitation/sexual inhibition inventory for women and
      men.
AB  - The purpose of the current investigation was to develop a scale that would assess
      propensity for sexual arousal in response to a broad range of stimuli and sexual
      situations in both men and women. In Study 1, data from a nonclinical sample of
      481 male and female students (graduate and undergraduate) were submitted to
      exploratory and confirmatory factor analyses in order to develop the Sexual
      Excitation/Sexual Inhibition Inventory for Women and Men (SESII-W/M), and gender
      differences on the subscales were tested. In Study 2, construct validity and test
      retest reliability of the SESII-W/M were assessed with a second sample of
      undergraduate students. The resultant measurement tool was comprised of six
      subscales: Inhibitory Cognitions, Relationship Importance, Arousability, Partner
      Characteristics and Behaviors, Setting (Unusual or Unconcealed), and Dyadic
      Elements of the Sexual Interaction. The measure demonstrated good test-retest
      reliability and discriminant and convergent validity. The SESII-W/M will likely
      be a useful measure in investigations in which sexual inhibition and sexual
      excitation must be assessed identically for men and women.

PMID- 19859800
TI  - Usual care psychotherapy for depression in a large managed behavioral health
      organization.
AB  - Evidence-based psychotherapies to treat depression are available, yet it remains
      unknown the extent to which these practices are used in routine care for
      depression. Using survey and administrative data, we sought to describe usual
      care psychotherapy for depression for adult patients receiving care through a
      large, managed behavioral health care organization. Data from 420 patients
      receiving psychotherapy for depression and 159 of their therapists provide
      evidence that some practitioners are using evidence-based psychotherapy
      techniques for depression, but also demonstrate the need for improved tools to
      monitor and improve quality of psychotherapy in usual care.

PMID- 19859801
TI  - Genomic screening for genes upregulated by demethylation revealed novel targets
      of epigenetic silencing in breast cancer.
AB  - Breast cancer arises through the accumulation of multiple genetic alterations and
      epigenetic changes such as methylation, which silences gene expression in a
      variety of cancers. In the present study, we applied genomic screening to
      identify genes upregulated by the demethylating agent 5-aza-2'-deoxycytidine
      (DAC) in a human breast cancer cell line (MCF7). We identified 288 genes
      upregulated and 29 genes downregulated more than fivefold after treatment with
      DAC, and gene ontology analyses revealed the genes to be involved in immune
      responses, apoptosis, and cell differentiation. In addition, real-time PCR
      analysis of ten genes silenced in MCF7 cells confirmed that they are upregulated
      by DAC, while bisulfite-pyrosequencing analysis confirmed that nine of those
      genes were silenced by methylation. We also found that treating MCF7 cells with
      DAC restored induction of DFNA5 by p53, as well as by two other p53 family genes,
      p63gamma and p73beta. Introduction of NTN4 into MCF7 cells suppressed cell
      growth, indicating that NTN4 has tumor suppressive activity. In primary breast
      cancers, we detected cancer-specific methylation of NTN4, PGP9.5, and DKK3,
      suggesting that methylation of these genes could be useful markers for diagnosis
      of breast cancer. Thus, DNA methylation appears to be a common event in breast
      cancer, and the genes silenced by methylation could be useful targets for both
      diagnosis and therapy.

PMID- 19859802
TI  - EGFR over-expression and activation in high HER2, ER negative breast cancer cell
      line induces trastuzumab resistance.
AB  - HER2 is gene amplified or over-expressed in 20-25% of breast cancers resulting in
      elevated HER2 activation. Trastuzumab (Herceptin), a humanized monoclonal
      antibody, targets activated HER2 and is clinically effective in HER2-over
      expressing breast cancers. However, despite prolonged survival, treated breast
      cancer patients develop resistance. Resistance to trastuzumab occurs upon
      inactivation of HER2 regulatory proteins or upon up-regulation of alternative
      receptors. In particular, elevated levels of EGFR, present in estrogen receptor
      (ER) positive, trastuzumab-resistant BT-474 xenografts caused, a trastuzumab
      resistant phenotype (Ritter et al. Clin Cancer Res 13:4909-4919, 2007). However,
      the role of EGFR in acquired trastuzumab resistance in ER negative cell models is
      not well defined. In this study, SKBR3 cell line clones expressing EGFR were
      generated to examine the role of EGFR over-expression on trastuzumab sensitivity
      in an, ER-negative breast carcinoma cell line. A stable clone, SKBR3/EGFR (clone
      4) expressing moderate levels of EGFR remained sensitive to trastuzumab, whereas
      a stable clone, SKBR3/EGFR (clone 5) expressing high levels of EGFR, became
      resistant to trastuzumab. Depletion of EGFR by EGFR small-interfering RNAs in the
      SKBR3/EGFR (clone 5) reversed trastuzumab resistance. However, the SKBR3/EGFR
      (clone 5) cell line remained sensitive to lapatinib, an EGFR/HER2 inhibitor.
      Biochemical analysis using co-immunoprecipitation and proximity-based
      quantitative VeraTag assays demonstrated that high levels of EGFR
      phosphorylation, EGFR/EGFR homo-dimerization, and EGFR/HER2 hetero-dimerization
      were present in the trastuzumab-resistant cells. We conclude that EGFR over
      expression can mediate trastuzumab resistance in both ER positive and ER negative
      cells and hypothesize that a threshold level of EGFR, in the absence of autocrine
      ligand production, is required to induce the resistant phenotype.

PMID- 19859803
TI  - No evidence for glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1
      in breast cancer risk.
AB  - Breast cancer is a complex disease and in recent years a number of breast cancer
      susceptibility genes have been identified, but the role of low penetrance
      susceptibility genes has not been completely resolved. Glutathione S-transferases
      (GSTs) are phase II xenobiotic metabolizing enzymes involved in the
      detoxification of chemical carcinogens and environmental pollutants and play an
      important role in cell defense mechanisms against oxidative stress. They have
      been in the spot light for the investigation of a potential association with
      breast cancer risk but so far, sparse or even no data for a potential
      contribution of GSTA2, GSTM2, GSTO, and GSTZ to breast cancer risk are available.
      We genotyped GSTA2_448_C > G (rs2180314), GSTA2_742_A > C (rs6577), GSTM2_-832_T
      > C (rs638820), GSTO1_-1242_G > A (rs2164624), GSTO1_419_A > C (rs4925), GSTO2_
      183_A > G (rs2297235), GSTO2_342_A > G (rs156697), GSTZ1_-4378_A > G (rs1046428),
      and GSTZ1_94_G > A (rs3177427) by MALDI-TOF MS in the German GENICA breast cancer
      case-control collection of 1021 cases and 1015 controls and performed breast
      cancer risk association in general and with respect to the stratifications:
      menopausal status, family history of breast or ovarian cancer, use of oral
      contraceptives, use of hormone therapy, body mass index, and smoking as well as
      histopathological tumor characteristics including hormone receptor status, grade,
      histology, and node status. We did not observe any breast cancer risk
      associations and conclude that it is unlikely that glutathione S-transferases
      GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 participate in breast cancer
      susceptibility.

PMID- 19859804
TI  - Analysis of breast cancer related gene expression using natural splines and the
      Cox proportional hazard model to identify prognostic associations.
AB  - Many studies correlating gene expression data to clinical parameters assume a
      linear increase or decrease of the clinical parameter under investigation with
      the expression of a gene. We have studied genes encoding important breast cancer
      related proteins using a model for survival-type data that is based on natural
      splines and the Cox proportional hazard model, thereby removing the linearity
      assumption. Expression data of 16 genes were studied in relation to metastasis
      free probability in a cohort of 295 consecutive breast cancer patients treated at
      The Netherlands Cancer Institute. The independent predictive power for disease
      outcome of the 16 individual genes was tested in a multivariable model with known
      clinical and pathological risk factors. There is a linear relationship between
      increasing expression and a higher or lower hazard for distant metastasis for
      ESR1, ERBB4, VEGF, CCNE2, EZH2, and UPA; for ERBB2, ERBB3, CCND1, CCNE1, EED,
      CXCR4, CCR7, SDF1, and PAI1 there is no clear increase or decrease; and for EGFR
      there seems to be a non-linear relation. Multivariable analysis showed that the
      70-gene prognosis profile outperforms all the other variables in the model
      (hazard-rate 5.4, 95% CI 2.5-11.7; P = 0.000018). EGFR-expression seems to have a
      non-linear relation with disease outcome, indicating that lower but also higher
      expression of EGFR are associated with worse outcome compared to intermediate
      expression levels; the other genes show no or a linear relation.

PMID- 19859805
TI  - Demographic responses of Daphnia magna fed transgenic Bt-maize.
AB  - The food/feed quality of a variety of genetically modified (GM) maize expressing
      Cry1Ab Bt-toxin was tested over the life-cycle of Daphnia magna, an arthropod
      commonly used as model organism in ecotoxicological studies. Demographic
      responses were compared between animals fed GM or unmodified (UM) near isogenic
      maize, with and without the addition of predator smell. Age-specific data on
      survival and birth rates were integrated and analysed using life tables and
      Leslie matrices. Survival, fecundity and population growth rate (PGR) data
      generally disfavoured transgenic Bt-maize as feed for D. magna compared to
      animals fed the unmodified (UM) near isogenic line of maize. Decomposition of age
      specific effects revealed that the most important contributions to a reduced PGR
      in the GM-fed group came from both fecundity and survival differences early in
      life. We conclude that juvenile and young adult stages are the most sensitive
      experimental units and should be prioritized in future research. These stages are
      often omitted in toxicological/ecotoxicological studies and in feeding trials.

PMID- 19859806
TI  - An experimental evaluation of the All Stars prevention curriculum in a community
      after school setting.
AB  - This study tested the effectiveness of a prevention curriculum, All Stars, as
      implemented in a year-long school-based after school program and provides an
      independent replication of the effects of All Stars on targeted mediators and
      problem behaviors using an experimental methodology. Middle school students (N =
      447) who registered for the after school program were randomly assigned to the
      experimental or control condition. The sample included approximately equal
      proportions of males and females, was 70% African American, and 59% of the
      students received subsidized meals at school. All Stars was delivered with
      reasonable integrity to the program design, although with lower quality than
      reported in earlier efficacy trials. However, actual student exposure to the
      program was lower than expected due to low levels of attendance in the after
      school program. Students who ever attended received an average of 16 h of All
      Stars instruction. Results showed no differences between the treatment and
      control students at post-test on any of the outcomes or mediators. Further, no
      positive effects were found for youths receiving higher dosage, higher quality
      program delivery, or both. Insufficient time to achieve high quality
      implementation in the after school context and potential deviancy training are
      suggested as reasons for the failure to replicate positive program effects.

PMID- 19859807
TI  - Immigration and weight gain: Mexican-American women's perspectives.
AB  - There is an urgent need for effective and accessible culturally-sensitive weight
      loss interventions for the Mexican-American population. It is imperative that
      cultural factors be taken into account when designing weight-loss interventions
      targeting this population. As a first step in this direction, this study examined
      the experiences, concerns, and beliefs regarding diet, weight and weight loss of
      Mexican-American immigrant women. Focus groups were conducted with Mexican
      American women (n = 25) between the ages of 20 and 63, from the Portland, Oregon
      metropolitan area. Major themes identified in the discussions included important
      lifestyle changes brought about by immigration, the challenges of adopting
      "American ways," lack of nutritional information, and the difficulties in making
      food choices given the complexities of the family context. Behavioral
      interventions must provide culturally-centered behavioral strategies addressing
      some of the difficulties identified in this study. Specific suggestions are
      provided for the development of weight-loss interventions for this population.

PMID- 19859808
TI  - Changes in the mechanical properties and residual strain of elastic tissue in the
      developing fetal aorta.
AB  - Formed almost exclusively during development, arterial elastic fibers must
      function for the lifetime of the animal. We have observed dramatic structural and
      mechanical changes in aortic elastic tissue during gestational and postnatal
      development. Elastic tissue was isolated from bovine aortas: (i) during late
      pregnancy and (ii) in adults. Changes in the relative content of aortic elastic
      tissue were assessed, as were the viscoelastic properties and residual strains of
      purified aortic elastic tissue rings. As aortic elastic tissue content increased
      during development, its circumference and thickness increased-but with
      circumference rising faster than wall thickness, causing a relative thinning of
      the elastic tissue. At the same time, elastic tissue stiffness increased while
      viscoelastic behavior decreased. Much of these changes were concentrated during
      late gestational development, such that the changes observed during the short
      span of late gestation examined (~60 days) were similar in magnitude to those
      occurring over the much longer postnatal period (approximately 1-2 years).
      Finally, we observed an approximately threefold increase in residual strain in
      aortic elastic tissue from fetal to adult life, with most of this increase again
      occurring in late gestation. These results suggest that rapid remodeling, as well
      as accumulation, of aortic elastic tissue occurs during late gestation. These
      changes significantly alter both fetal aortic mechanical properties and residual
      stresses.

PMID- 19859809
TI  - Mesh morphing and response surface analysis: quantifying sensitivity of vertebral
      mechanical behavior.
AB  - Vertebrae provide essential biomechanical stability to the skeleton. In this work
      novel morphing techniques were used to parameterize three aspects of the geometry
      of a specimen-specific finite element (FE) model of a rat caudal vertebra
      (process size, neck size, and end-plate offset). Material properties and loading
      were also parameterized using standard techniques. These parameterizations were
      then integrated within an RSM framework and used to produce a family of FE
      models. The mechanical behavior of each model was characterized by predictions of
      stress and strain. A metamodel was fit to each of the responses to yield the
      relative influences of the factors and their interactions. The direction of
      loading, offset, and neck size had the largest influences on the levels of
      vertebral stress and strain. Material type was influential on the strains, but
      not the stress. Process size was substantially less influential. A strong
      interaction was identified between dorsal-ventral offset and dorsal-ventral off
      axis loading. The demonstrated approach has several advantages for spinal
      biomechanical analysis by enabling the examination of the sensitivity of a
      specimen to multiple variations in shape, and of the interactions between shape,
      material properties, and loading.

PMID- 19859810
TI  - The understanding of word definitions in school-age children.
AB  - This study investigated children's understanding of unfamiliar noun and verb
      definitions in tasks that were manipulated for syntactic and semantic properties
      of definitions. The study was also designed to examine the relation between
      understanding word definitions and the skills of syntactic awareness and making
      inferences. A total of 117 children over three upper elementary grades (3, 4, 5)
      participated in the study. The definitional tasks were presented in multiple
      choice format, with each definition followed by four context sentences. In the
      syntactic/semantic condition, which included nouns and verbs, the context
      sentences were manipulated for syntactic and semantic properties. In the semantic
      condition, which included only nouns, the context sentences were manipulated only
      for semantics. All children also completed a syntactic awareness task and a
      making inferences task. Results indicated that children did not make significant
      grade improvements in the semantic task, but did so in the syntactic/semantic
      task, suggesting the dependence of syntactic cues on definitional understanding.
      Findings further suggested that inferencing and syntactic awareness are important
      to children's ability in understanding a definition for an unfamiliar word and to
      integrating that meaning into a context sentence.

PMID- 19859811
TI  - Health promoting habits of people who pray for their health.
AB  - To determine the health habits of people who pray for their health, data from the
      National Health Interview Survey was analyzed for health habits of people who
      prayed or did not pray for their health. Of the 22,314 respondents, 13,179 (59%)
      prayed for their health. These individuals saw a physician more frequently,
      participated more frequently in vigorous exercise and used more relaxation
      techniques, support groups, meditation and complimentary and alternative medicine
      therapies. People who pray for their health participate in more health promoting
      behaviors than people who do not pray for their health.

PMID- 19859812
TI  - Tape underlayment rotary-node (TURN) valves for simple on-chip microfluidic flow
      control.
AB  - We describe a simple and reliable fabrication method for producing multiple,
      manually activated microfluidic control valves in polydimethylsiloxane (PDMS)
      devices. These screwdriver-actuated valves reside directly on the microfluidic
      chip and can provide both simple on/off operation as well as graded control of
      fluid flow. The fabrication procedure can be easily implemented in any soft
      lithography lab and requires only two specialized tools-a hot-glue gun and a
      machined brass mold. To facilitate use in multi-valve fluidic systems, the mold
      is designed to produce a linear tape that contains a series of plastic rotary
      nodes with small stainless steel machine screws that form individual valves which
      can be easily separated for applications when only single valves are required.
      The tape and its valves are placed on the surface of a partially cured thin PDMS
      microchannel device while the PDMS is still on the soft-lithographic master, with
      the master providing alignment marks for the tape. The tape is permanently
      affixed to the microchannel device by pouring an over-layer of PDMS, to form a
      full-thickness device with the tape as an enclosed underlayment. The advantages
      of these Tape Underlayment Rotary-Node (TURN) valves include parallel fabrication
      of multiple valves, low risk of damaging a microfluidic device during valve
      installation, high torque, elimination of stripped threads, the capabilities of
      TURN hydraulic actuators, and facile customization of TURN molds. We have
      utilized these valves to control microfluidic flow, to control the onset of
      molecular diffusion, and to manipulate channel connectivity. Practical
      applications of TURN valves include control of loading and chemokine release in
      chemotaxis assay devices, flow in microfluidic bioreactors, and channel
      connectivity in microfluidic devices intended to study competition and
      predator/prey relationships among microbes.

PMID- 19859813
TI  - Ethnicity and persistent symptom burden in breast cancer survivors.
AB  - INTRODUCTION: Relatively few studies of breast cancer survivors have included
      nonwhite women or women who do not speak English. METHODS: We administered a
      survey to patients who were >or=3 months post-completion of their adjuvant
      treatment for stage 0-III breast cancer at Columbia University Medical Center in
      order to assess the prevalence of 16 physical and emotional symptoms and identify
      sociodemographic factors associated with these symptoms. Univariate analysis,
      factor analysis, ANOVA, and multiple linear regression analysis were performed.
      RESULTS: Of 139 patients surveyed, 58 were white, 63 Hispanic, and 18 black. The
      symptom most commonly reported was fatigue(76%), and the most common severe
      symptom was muscle aches(40%). Most patients(70%) complained of >or=6 symptoms.
      Hispanic women were more likely to report >10 symptoms (p < 0.05). Factor
      analysis reduced the 16 symptoms to 4 underlying symptom clusters that we
      categorized as 'depression', 'chemotherapy', 'hormone', and 'pain'-related. In
      the multiple linear regression models, Hispanic women were more likely to report
      chemotherapy-related symptoms (p < 0.05) and pain-related symptoms (p < 0.05).
      Unemployed women were more likely to report chemotherapy-related symptoms (p <
      0.05). Women <45 years old were less likely to report chemotherapy (p < 0.05) and
      pain-related symptoms (p < 0.05). CONCLUSIONS: The majority of women in this
      study, particularly those who were Hispanic, elderly, or unemployed, experienced
      persistent symptoms, most commonly fatigue and muscle aches. IMPLICATIONS FOR
      CANCER SURVIVORS: Because Hispanic, elderly, or unemployed women experience
      greater symptom burden, efforts should made to address their unique needs.

PMID- 19859814
TI  - Comparison on in vitro characterization of fucospheres and chitosan microspheres
      encapsulated plasmid DNA (pGM-CSF): formulation design and release
      characteristics.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine used in
      the treatment of serious conditions resulting from chemotherapy and bone marrow
      transplantation such as neutropenia and aplastic anemia. Despite these effects,
      GM-CSF has a very short biological half-life, and it requires frequent injection
      during the treatment. Therefore, the cytokine production is possible in the body
      with plasmid-encoded GM-CSF (pGM-CSF) coding for cytokine administered to the
      body. However, the selection of the proper delivery system for the plasmid is
      important. In this study, two different delivery systems, encapsulated plasmid
      such as fucoidan-chitosan (fucosphere) and chitosan microspheres, were prepared
      and the particle physicochemical properties evaluated. Fucospheres and chitosan
      microspheres size ranges are 151-401 and 376-681 nm. The zeta potential values of
      the microspheres were changed between 8.3-17.1 mV (fucosphere) and +21.9-28.9 mV
      (chitosan microspheres). The encapsulation capacity of fucospheres changed
      between 84.2% and 94.7% depending on the chitosan molecular weight used in the
      formulation. In vitro plasmid DNA release from both delivery systems exhibited
      slower profiles of approximately 90-140 days. Integrity of released samples was
      checked by agarose gel electrophoresis, and any additional band was not seen. All
      formulations were analyzed kinetically. The calculated regression coefficients
      showed a higher r2 value with zero-order kinetics. In conclusion, the
      characterizations of the microspheres can be modulated by changing the
      formulation variables, and it can be concluded that fucospheres might be a
      potential carrier system for the controlled delivery of GM-CSF encoding plasmid
      DNA.

PMID- 19859816
TI  - Mathematical modeling and the epidemiological research process.
AB  - The authors of this paper advocate for the expanded use of mathematical models in
      epidemiology and provide an overview of the principles of mathematical modeling.
      Mathematical models can be used throughout the epidemiological research process.
      Initially they may help to refine study questions by visually expressing complex
      systems, directing literature searches, and identifying sensitive variables. In
      the study design phase, models can be used to test sampling strategies, to
      estimate sample size and power, and to predict outcomes for studies impractical
      due to time or ethical considerations. Once data are collected, models can assist
      in the interpretation of results, the exploration of causal pathways, and the
      combined analysis of data from multiple sources. Finally, models are commonly
      used in the process of applying research findings to public health practice by
      estimating population risk, predicting the effects of interventions, and
      contributing to the evaluation of ongoing programs. Mathematical modeling has the
      potential to make significant contributions to the field of epidemiology by
      enhancing the research process, serving as a tool for communicating findings to
      policymakers, and fostering interdisciplinary collaboration.

PMID- 19859815
TI  - Herb-drug interactions with St John's wort (Hypericum perforatum): an update on
      clinical observations.
AB  - St John's wort (SJW) extracts, prepared from the aerial parts of Hypericum
      perforatum, contain numerous pharmacologically active ingredients, including
      naphthodianthrones (e.g., hypericin and its derivatives), phloroglucinols
      derivatives (e.g., hyperforin, which inhibits the reuptake of a number of
      neurotransmitters, including serotonin), and flavonoids. Such extracts are widely
      used for the treatment of mild-to-moderate depression. As a monotherapy, SJW has
      an encouraging safety profile. However, relevant and, in some case, life
      threatening interactions have been reported, particularly with drugs which are
      substrate of cytochrome P450 and/or P-glycoprotein. Well-documented SJW
      interactions include (1) reduced blood cyclosporin concentration, as suggested by
      multiple case reports as well as by clinical trials, (2) serotonin syndrome or
      lethargy when SJW was given with serotonin reuptake inhibitors, (3) unwanted
      pregnancies in women while using oral contraceptives and SJW, and (4) reduced
      plasma drug concentration of antiretroviral (e.g., indinavir, nevirapine) and
      anticancer (i.e., irinotecan, imatinib) drugs. Hyperforin, which is believed to
      contribute to the antidepressant action of St John's wort, is also strongly
      suspected to be responsible of most of the described interactions.

PMID- 19859817
TI  - Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells
      correlates with metastasis.
AB  - The chemokine receptor CXCR4 is involved in the metastasis of many cancers.
      Recent evidence suggests that CXCR4 may be also involved in the metastasis of
      renal cell carcinoma. We analyzed the expression of CXCR4 in primary carcinomas,
      metastatic tissues and normal tissues using immunohistochemistry. We further
      investigated the migration of renal carcinoma cells in response to stimulation by
      CXCL12 in vitro. We also studied the subcellular localization of CXCR4 in renal
      cell carcinoma cells in response to CXCL12 by confocal microscopy. We observed
      the highest percentage of CXCR4 expression in renal cell carcinoma metastases
      compared with that in renal cell carcinomas and normal renal tissues. We further
      found that CXCR4 was localized predominantly in the membrane in primary renal
      cell carcinomas and predominantly in the cytoplasm in renal cell carcinoma
      metastases. Moreover, we found that CXCR4 was translocated from the cytoplasmic
      membrane to the cytoplasm upon stimulation by its ligand CXCL12. Renal cell
      carcinoma metastasis was associated with higher expression of CXCR4 and
      interaction of CXCR4 and its ligand CXCL12 resulted in the internalization of
      CXCR4 from the cytoplasmic membrane. These findings implicate the CXCR4-CXCL12
      axis in the metastasis of renal cell carcinoma.

PMID- 19859818
TI  - A winding road to origin discovery.
AB  - Studies in our laboratory over the last three decades have shown that the Chinese
      hamster dihydrofolate reductase (DHFR) origin of replication corresponds to a
      broad zone of inefficient initiation sites distributed throughout the spacer
      between the convergently transcribed DHFR and 2BE2121 genes. It is clear from
      mutational analysis that none of these sites is genetically required for
      controlling origin activity. However, the integrity of the promoter of the DHFR
      gene is needed to activate the downstream origin, while the 3' processing signals
      prevent invasion and inactivation of the downstream origin by transcription
      forks. Several other origins in metazoans have been shown to correspond to zones
      of inefficient sites, while a different subset appears to be similar to the fixed
      replicators that characterize origins in S. cerevisiae and lower organisms. These
      observations have led us to suggest a model in which the mammalian genome is
      dotted with a hierarchy of degenerate, redundant, and inefficient replicators at
      intervals of a kilobase or less, some of which may have evolved to be highly
      circumscribed and efficient. The activities of initiation sites are proposed to
      be largely regulated by local transcription and chromatin architecture. Recently,
      we and others have devised strategies for identifying active origins on a genome
      wide scale in order to define their distributions between fixed and dispersive
      origin types and to detect relationships among origins, genes, and epigenetic
      markers. The global pictures emerging are suggestive but far from complete and
      appear to be plagued by some of the same uncertainties that have led to
      conflicting views of individual origins in the past (particularly DHFR). In this
      paper, we will trace the history of origin discovery in mammalian genomes,
      primarily using the well-studied DHFR origin as a model, because it has been
      analyzed by nearly every available origin mapping technique in several different
      laboratories, while many origins have been identified by only one. We will
      address the strengths and shortcomings of the various methods utilized to
      identify and characterize origins in complex genomes and will point out how we
      and others were sometimes led astray by false assumptions and biases, as well as
      insufficient information. The goal is to help guide future experiments that will
      provide a truly comprehensive and accurate portrait of origins and their
      regulation. After all, in the words of George Santayana, "Those who do not learn
      from history are doomed to repeat it."

PMID- 19859819
TI  - Prediction of daily ground-level ozone concentration maxima over New Delhi.
AB  - The pollution levels in New Delhi from industrial, residential, and
      transportation sources are continuously growing. As one of the major pollutants,
      ground-level ozone is responsible for various adverse effects on both humans and
      foliage. The present study aims to predict daily ground-level ozone concentration
      maxima over a site situated in New Delhi through neural networks (NN) and
      multiple-regression (MR) analysis. Although these methodologies are case and site
      specific, they are being developed and used widely. Therefore, to test these
      methodologies for New Delhi where no such study is available for ground-level
      ozone, six models have been developed based on NNs and MR using the same input
      data set. The changes in the performance capability of the two methods are
      sensitive to the selection of input parameters. The results are encouraging, and
      remarkable improvements in the performance of the models have been observed.

PMID- 19859820
TI  - Application of multivariate statistical methods for groundwater physicochemical
      and biological quality assessment in the context of public health.
AB  - Three representative areas (lowland, semi-mountainous, and coastal) have been
      selected for the collection of drinking water samples, and a total number of 28
      physical, chemical, and biological parameters per water sample have been
      determined and analyzed. The mean values of the physical and chemical parameters
      were found to be within the limits mentioned in the 98/83/EEC directive. The
      analysis of biological parameters shows that many of the water samples are
      inadequate for human consumption because of the presence of bacteria. Cluster
      analysis (CA) first was used to classify sample sites with similar properties and
      results in three groups of sites; discriminant analysis (DA) was used to
      construct the best discriminant functions to confirm the clusters determined by
      CA and evaluate the spatial variations in water quality. The standard mode
      discriminant functions, using 17 parameters, yielded classification matrix
      correctly assigning 96.97% of the cases. In the stepwise mode, the DA produced a
      classification matrix with 96.36% correct assignments using only ten parameters
      (EC, Cl-, NO3-, HCO3-, CO3(-2), Ca+2, Na+, Zn, Mn, and Pb). CA and factor
      analysis (FA) are used to characterize water quality and assist in water quality
      monitoring planning. CA proved that two major groups of similarity (six
      subclusters) between 17 physicochemical parameters are formed, and FA extracts
      six factors that account for 66.478% of the total water quality variation, when
      all samples' physicochemical data set is considered. It is noteworthy that the
      classification scheme obtained by CA is completely confirmed by principal
      component analysis.

PMID- 19859821
TI  - Study on the hydrogeochemical characteristics in groundwater, post- and pre
      tsunami scenario, from Portnova to Pumpuhar, southeast coast of India.
AB  - Natural hazards cause great damage to humankind and the surrounding ecosystem.
      They can cast certain indelible changes on the natural system. One such tsunami
      event occurred on 26 December 2004 and caused serious damage to the environment,
      including deterioration of groundwater quality. This study addresses the
      groundwater quality variation before and after the tsunami from Pumpuhar to
      Portnova in Tamil Nadu coast using geochemical methods. As a part of a separate
      Ph.D. study on the salinity of groundwater from Pondicherry to Velankanni, water
      quality of this region was studied with the collection of samples during November
      2004, which indicated that shallow aquifers were not contaminated by sea water in
      certain locations. These locations were targeted for post-tsunami sample
      collection during the months of January, March and August 2005 from shallow
      aquifers. Significant physical mixing (confirmed with mixing models) within the
      aquifer occurred during January 2005, followed by precipitation of salts in March
      and complete leaching and dissolution of these salts in the post-monsoon season
      of August. As a result, maximum impact of tsunami water was observed in August
      after the onset of monsoon. Tsunami water inundated inland water bodies and
      topographic lows where it remained stagnant, especially in the near-shore
      regions. Maximum tsunami inundation occurred along the fluvial distributary
      channels, and it was accelerated by topography to a certain extent where the
      southern part of the study area has a gentler bathymetry than the north.

PMID- 19859822
TI  - Stormwater metal loading to a well-mixed/stratified estuary (Sydney Estuary,
      Australia) and management implications.
AB  - Stormwater modelling indicated an average annual discharge from Sydney estuary
      catchment of 215,300 mL and loadings of 0.8, 0.5, 1.7, 3.2, 1.1, 3.6 and 17.7
      tonnes for As, Cd, Cr, Cu, Ni, Pb and Zn, respectively. Priority for remediation
      should be given to creeks with high-metal loads in the upper and central estuary,
      as well as discharging to the western shores of Middle Harbour. Managerial
      strategies need to target dissolved and particulate metal phases to ensure
      effective remediation. The proportion of metals discharged under low- (<5 mm
      rainfall/day), medium- (>5 to <50 mm/day) and high-flow conditions (>50 mm/day)
      was approximately 10%, 60% and 30% of total loading, respectively. Under high
      flow conditions the estuary becomes stratified and most metals are exported to
      the sea, whereas metals discharged during low-flow may be remediated by
      infiltration. Effective remediation will depend on the extent to which 'first
      flush' metals associated with medium-flow conditions can be remediated.

PMID- 19859823
TI  - Analysis of urban effects on soil temperature in Ankara.
AB  - In this study, data from two different meteorology stations were analyzed in
      order to reveal the effects of the urbanization on the soil temperature. These
      stations are the Ankara Meteorology Station (AMS), showing the urban effects, and
      the Esenboga Meteorology Station (EMS), showing the rural effects. The soil
      temperatures measured at depths of 5, 10, 20, and 50 cm at 0700, 1400, and 2100
      hours between 1960 and 2005 were used in the analysis. Long-term mean monthly
      temperatures at each depth and at each time considered were calculated and
      analyzed using Sen's slope and Mann-Kendall tests. The results showed that the
      mean monthly urban soil temperatures were generally higher than the rural soil
      temperatures. The differences between temperatures measured at 5, 10, 20, and 50
      cm in urban and rural stations (DeltaT(s(AMS-EMS))) ranged between 1.8 degrees C
      and 2.1 degrees C. As in the urban heat islands, the differences between the
      urban and rural soil temperatures are high at 2100 hours and low at 1400 hours.
      It was also observed that, due to the increasing number of buildings around the
      Esenboga Station in recent years, the difference between the urban and rural soil
      temperatures seems to have become smaller. These show that the factors affecting
      the urban heat islands and those affecting the soil temperatures are similar.
      Also, the temperature differences were observed to be higher during the warm
      season than in the cold season. The frequency distributions of the temperature
      differences (DeltaT(s(AMS-EMS))) reveal both positive and negative values.
      However, the positive temperature differences are obviously prevalent.

PMID- 19859824
TI  - Objective assessment of sperm motion characteristics of Malpura ram lambs raised
      under intensive management system in semiarid tropical environment.
AB  - A study was conducted to evaluate the semen production and sperm motion
      characteristics of ram lambs by computer-aided semen analysis technique. Eight
      Malpura rams were raised under intensive management system and were trained for
      semen collection at a weekly interval from the age of 6 months. Rams were
      scheduled for semen collection at a weekly interval up to 1 year of age to assess
      their potential for semen production and objective evaluation of semen quality.
      The average age of ram lambs at the time of first ejaculation was 219 days
      ranging from 186 to 245 days. The age of ram lambs significantly (p < 0.05)
      influenced sperm concentration, sperm velocities, and beat frequency of
      spermatozoa, which were higher in 9-12-month-old compared to 6-9-month-old ram
      lambs. However, the effect of age was not significant on semen volume, percent
      motility, percent rapid, medium or slow motile spermatozoa, percent linearity,
      percent straightness, amplitude of lateral head displacement, percent elongation,
      and area of sperm head. The body weight of ram lambs was significantly (p < 0.01)
      and positively correlated (r = 0.46) with age. The results indicate that Malpura
      ram lambs of 9-12 months of age raised under the intensive management system in a
      semiarid tropical environment can produce good quality of semen.

PMID- 19859825
TI  - Infection control measures to prevent invasive mould diseases in hematopoietic
      stem cell transplant recipients.
AB  - Invasive mould diseases, particularly aspergillosis, are important causes of
      morbidity and mortality in allogeneic stem cell transplant recipients. Mould
      spores are ubiquitous in the environment. Guidelines established by the Centers
      for Disease Control (CDC) and other authoritative organizations focus on
      approaches to reduce exposure to mould spores. These recommendations include
      avoidance of areas and activities expected to result in high levels of mould
      spores (e.g., construction, gardening) and use of specially designed units
      (protected environments) where additional standards (e.g., HEPA-filtered rooms)
      are in place to minimize mould exposure. These recommendations are based on
      consensus criteria and limited clinical data largely derived from single-center
      retrospective studies. In addition, highly immunocompromised stem cell transplant
      recipients are commonly managed as outpatients, where engineering standards of
      the inpatient protected environment are not feasible. In the absence of an
      outbreak with an identified environmental source (e.g., a contaminated air vent),
      it is not possible to reliably distinguish community-acquired from nosocomial
      aspergillosis. Adherence to infection control guidelines, acknowledging their
      limitations, combined with evidence-based targeted antifungal prophylaxis for the
      highest risk transplant recipients, is likely to be the most effective approach
      to prevent invasive mould diseases.

PMID- 19859826
TI  - Structural genomics target selection for the New York consortium on membrane
      protein structure.
AB  - The New York Consortium on Membrane Protein Structure (NYCOMPS), a part of the
      Protein Structure Initiative (PSI) in the USA, has as its mission to establish a
      high-throughput pipeline for determination of novel integral membrane protein
      structures. Here we describe our current target selection protocol, which applies
      structural genomics approaches informed by the collective experience of our team
      of investigators. We first extract all annotated proteins from our reagent
      genomes, i.e. the 96 fully sequenced prokaryotic genomes from which we clone DNA.
      We filter this initial pool of sequences and obtain a list of valid targets.
      NYCOMPS defines valid targets as those that, among other features, have at least
      two predicted transmembrane helices, no predicted long disordered regions and,
      except for community nominated targets, no significant sequence similarity in the
      predicted transmembrane region to any known protein structure. Proteins that feed
      our experimental pipeline are selected by defining a protein seed and searching
      the set of all valid targets for proteins that are likely to have a transmembrane
      region structurally similar to that of the seed. We require sequence similarity
      aligning at least half of the predicted transmembrane region of seed and target.
      Seeds are selected according to their feasibility and/or biological interest, and
      they include both centrally selected targets and community nominated targets. As
      of December 2008, over 6,000 targets have been selected and are currently being
      processed by the experimental pipeline. We discuss how our target list may impact
      structural coverage of the membrane protein space.

PMID- 19859827
TI  - Adenosine regulates thrombomodulin and endothelial protein C receptor expression
      in folliculostellate cells of the pituitary gland.
AB  - Adenosine stimulates the release of interleukin 6 (IL-6) and vascular endothelial
      growth factor from folliculostellate cells of the anterior pituitary gland
      indicating that such cells are also involved in the communication between the
      immune and endocrine systems during stress and inflammation. In order to
      understand the precise actions of adenosine on folliculostellate cells, DNA
      microarray analysis was used to determine global changes in gene expression.
      Hierarchical clusters revealed, of the genes that had altered expression, the
      majority were suppressed and many, such as B cell translocation gene 2 and cyclin
      dependent kinase inhibitor 2b were related to cell cycle arrest or inhibition of
      proliferation. Several of the up-regulated genes were associated with cytokine
      signalling or membrane receptor activity. The most notable of these being IL-6,
      sulfiredoxin 1, endothelial protein C receptor (EPCR) and thrombomodulin (THBD)
      which can all play a role in controlling inflammation. The EPCR and THBD pathway
      is well known in anti-coagulation but also has anti-inflammatory and anti
      apoptotic properties. Up-regulation of EPCR and THBD in folliculostellate cells
      was confirmed by qRT-PCR and western blotting analysis and their expression were
      also demonstrated in many of the hormone-secreting cells of the anterior
      pituitary gland. Our findings suggest that adenosine can stimulate expression of
      stress and inflammation related genes from folliculostellate cells of the
      anterior pituitary gland. These genes include EPCR and THBD, neither of which has
      been previously identified in the pituitary gland.

PMID- 19859828
TI  - Uncertainties.
AB  - In contemporary science uncertainty is often represented as an intrinsic feature
      of natural and of human phenomena. As an example we need only think of two
      important conceptual revolutions that occurred in physics and logic during the
      first half of the twentieth century: (1) the discovery of Heisenberg's
      uncertainty principle in quantum mechanics; (2) the emergence of many-valued
      logical reasoning, which gave rise to so-called 'fuzzy thinking'. I discuss the
      possibility of applying the notions of uncertainty, developed in the framework of
      quantum mechanics, quantum information and fuzzy logics, to some problems of
      political and social sciences.

PMID- 19859829
TI  - Manufacturing mistrust: issues in the controversy regarding foster children in
      the pediatric HIV/AIDS clinical trials.
AB  - The use of foster children as subjects in the pediatric HIV/AIDS clinical trials
      has been the subject of media controversy, raising a range of ethical and social
      dimensions. Several unsettled issues and debates in research ethics underlie the
      controversy and the lack of consensus among professional researchers on these
      issues was neither adequately appreciated nor presented in media reports. These
      issues include (1) the tension between protecting subjects from research risk
      while allowing them access to the possible benefits of research; (2) the blurring
      of the potentially conflicting roles of investigator and physician and the
      boundaries between research and therapy; (3) the adequacy of Institutional Review
      Board oversight; and (4) trust and the relationships among physicians,
      investigators and industry. The media controversy about the pediatric HIV/AIDS
      clinical trials can be seen as a means of "manufacturing mistrust" in health
      care, research and social services that have not always met the needs and
      expectations of the public. In an era of emerging infections, it is critical to
      the public's health that people understand the role of rigorous and ethical
      research in the development of safe and effective care. Investigators,
      journalists and the public need to become knowledgeable about major ethical
      issues in the conduct of research in order to engage in dialogue about balancing
      research risks and benefits and to be able to distinguish fact from distortion in
      an era of multiple and rapid transmission of information.

PMID- 19859831
TI  - Erythropoietin promotes deleterious cardiovascular effects and mortality risk in
      a rat model of chronic sports doping.
AB  - Athletes who abuse recombinant human erythropoietin (rhEPO) consider only the
      benefit to performance and usually ignore the potential short and long-term
      liabilities. Elevated haematocrit and dehydratation associated with intense
      exercise may reveal undetected cardiovascular risk, but the mechanisms underlying
      it remain to be fully explained. This study aimed to evaluate the cardiovascular
      effects of rhEPO in rats under chronic aerobic exercise. A ten week protocol was
      performed in four male Wistar rat groups: control--sedentary; rhEPO--50 IU kg(
      1), 3 times/wk; exercised (EX)--swimming for 1 h, 3 times/wk; EX + rhEPO. One rat
      of the EX + rhEPO group suffered a sudden death episode during the week 8. rhEPO
      in trained rats promoted erythrocyte count increase, hypertension, heart
      hypertrophy, sympathetic and serotonergic overactivation. The suddenly died rat's
      tissues presented brain with vascular congestion; left ventricular hypertrophy,
      together with a "cardiac-liver", suggesting the hypothesis of heart failure as
      cause of sudden death. In conclusion, rhEPO doping in rats under chronic exercise
      promotes not only the expected RBC count increment, suggesting hyperviscosity,
      but also other serious deleterious cardiovascular and thromboembolic
      modifications, including mortality risk, which might be known and assumed by all
      sports authorities, including athletes and their physicians.

PMID- 19859830
TI  - Regulating functional cell fates in CD8 T cells.
AB  - The attributes of specificity and memory enable CD8(+) T cells to provide long
      lasting protection against a variety of challenges. Although, the importance of
      CD8(+) T cells for protection against intracellular infections and transformation
      is well-established, the functional type; effector phenotypes (Tc1, Tc2, Tc17
      and/or Tcreg) and/or memory (effector or central), of CD8(+) T cells most
      desirable for tumor immunity is not established. To determine the tumor efficacy
      of various effector types and/or memory CD8 T cells, it is imperative to better
      understand intrinsic and extrinsic factors that regulate CD8(+) T cell
      differentiation and use this information to generate and test distinct functional
      cell types in tumor models. The focus of our laboratory investigations is to
      identify the extrinsic factors such as antigen strength, co-stimulatory
      molecules, cytokines, and small molecule modifiers that regulate intrinsic
      programs for various effector and/or memory cell fate in antigen specific CD8 T
      cells. The use of this information to generate immunity in murine tumor models
      has facilitated development of new adoptive cell transfer (ACT) as well as
      immunization strategies for cancer treatment.

PMID- 19859832
TI  - Comparison of hematoma shape and volume estimates in warfarin versus non-warfarin
      related intracerebral hemorrhage.
AB  - BACKGROUND: Hematoma volume is a major determinant of outcome in patients with
      intracerebral hemorrhage (ICH). Accurate volume measurements are critical for
      predicting outcome and are thought to be more difficult in patients with oral
      anticoagulation-related ICH (OAT-ICH) due to a higher frequency of irregular
      shape. We examined hematoma shape and methods of volume assessment in patients
      with OAT-ICH. METHODS: We performed a case-control analysis of a prospectively
      identified cohort of consecutive patients with ICH. We retrospectively reviewed
      50 consecutive patients with OAT-ICH and 50 location-matched non-OAT-ICH
      controls. Two independent readers analyzed CT scans for hematoma shape and volume
      using both ABC/2 and ABC/3 methods. Readers were blinded to all clinical
      variables including warfarin status. Gold-standard ICH volumes were determined
      using validated computer-assisted planimetry. RESULTS: Within this cohort, median
      INR in patients with OAT-ICH was 3.2. Initial ICH volume was not significantly
      different between non-OAT-ICH and OAT-ICH (35 +/- 38 cc vs. 53 +/- 56 cc, P =
      0.4). ICH shape did not differ by anticoagulation status (round shape in 10% of
      OAT-ICH vs. 16% of non-OAT-ICH, P = 0.5). The ABC/3 calculation underestimated
      median volume by 9 (3-28) cc, while the ABC/2 calculation did so by 4 (0.8-12)
      cc. CONCLUSIONS: Hematoma shape was not statistically significantly different in
      patients with OAT-ICH. Among bedside approaches, the standard ABC/2 method offers
      reasonable approximation of hematoma volume in OAT-ICH and non-OAT-ICH.

PMID- 19859833
TI  - How I manage the adult potential organ donor: donation after cardiac death (part
      2).
AB  - To address the gap between organs available for transplant and the number of
      patients on the transplant waiting list, the Joint Commission on the
      Accreditation of Healthcare Organizations, Institute of Medicine, United Network
      for Organ Sharing and the federal government have recommended the increased used
      of donation after cardiac death (DCD) (JCAHOnline
      http://www.jointcommission.org/Library/JCAHOnline/jo_06.06.htm ; UNOS, Highlights
      of the June Board Meeting, 2006). DCD is defined as organ donation once death is
      declared after irreversible cessation of circulatory and respiratory functions,
      as opposed to brain death (donation after neurological death). Though DCD is one
      of the fastest growing categories of organ donors, it comprises only 8% of all
      deceased donors (Steinbrook in N Engl J Med 357:209-213, 2007). Prior to 1968,
      when the Ad Hoc Committee of Harvard Medical School proposed a neurological
      definition of death based on brain-death criteria, organs from deceased donors
      came from patients who had suffered cardio-pulmonary demise (IOM, Non-heart
      beating organ transplantation: practice and protocols, 2000). Early
      transplantation from DCD donors met with limited success and most transplant
      surgeons turned to brain-dead donors. Consequently, DCD fell out of vogue and,
      until recently, has not been the focus of transplant initiatives.

PMID- 19859834
TI  - Gender-related differences in upper gastrointestinal endoscopic findings: an
      assessment of 4,700 cases from Iran.
AB  - BACKGROUND AND OBJECTIVE: Regarding the high prevalence of gastrointestinal
      symptoms in our country, the probable overuse or even late usage of upper
      gastrointestinal endoscopy for unnecessary reasons and gender influences on both
      internal and external fate and effects, we decided to evaluate the gender-related
      differences in upper gastrointestinal endoscopic findings to provide
      gastroenterologists with information which they can perform better interpretation
      of their patient's symptoms before performing upper gastrointestinal endoscopy.
      DESIGN: A descriptive cross-sectional study performed to evaluate gender-related
      differences in the upper endoscopy findings. SETTING: The study was performed in
      the upper endoscopy ward of a general hospital in Tehran, Iran. PATIENTS: Four
      thousand and seven hundred Iranian patients undergo upper endoscopy between 1992
      and 2002. MAIN OUTCOME MEASUREMENTS: Upper endoscopy findings RESULTS: After age
      adjustment, oesophageal tumour, gastroesophageal reflux disease (GERD), gastric
      tumour, oesophageal varices, gastritis, hiatal hernia, gastric ulcer and erosive
      gastropathy, all p < 0.001 were significantly more common among men rather than
      women. Male gender predicts the presence of hiatal hernia (odds ratio (OR) = 1.9,
      p < 0.001), GERD (OR = 1.6, p < .001), gastric ulcer (OR = 2.3, p < 0.001),
      duodenal ulcer (OR = 2.3, p < 0.001) and duodenal varices (OR = .6, p = .044).
      LIMITATION: Backward study CONCLUSION: Our regression models revealed that male
      gender is a risk factor for hiatal hernia, GERD, gastric ulcer and duodenal ulcer
      but not for other upper endoscopic findings.

PMID- 19859836
TI  - Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor
      pathway inhibitor in patients with hyperthyroidism.
AB  - Various abnormalities of coagulation-fibrinolytic system have been reported in
      patients with thyroid dysfunction. Several studies indicate that coagulation and
      fibrinolytic system is disturbed in the patients with hyperthyroidism. The levels
      of plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and tissue
      factor pathway inhibitor (TFPI) have been very rarely investigated in patients
      with hyperthyroidism. Therefore, the main purpose of this study was to evaluate
      the profile of coagulation and fibrinolytic parameters including TAFI and TFPI in
      patients with hyperthyroidism. We also investigated the relationships between
      serum thyroid hormones and hemostatic parameters in these patients. Thirty
      patients with untreated hyperthyroidism and 25 age- and sex-matched healthy
      controls were included in the study. Factor V (FV), protein C, protein S, TFPI,
      and TAFI were measured. The relationships between serum thyroid hormones and
      these hemostatic parameters were examined. Compared with the control subjects,
      TAFI Ag levels were increased significantly in patients with hyperthyroidism
      [mean +/- SD (ranges)] [177.03 +/- 20.37 (131-206%) versus 145.9 +/- 23.0 (89
      169%)] (P < 0.001), whereas FV [89.8 +/- 21.02 (49-124%) versus 116.1 +/- 31.4
      (56.4-200%)], protein C [72.8 +/- 46.22 (2-149%) versus 144.0 +/- 26.3 (74-158%)]
      and protein S [60.06 +/- 42.82 (9-156%) versus 151 +/- 33 (76-231%)] activities
      and TFPI Ag levels [69.56 +/- 17.63 (39-140 ng/ml) versus 87.5 +/- 15.9 (64-121
      ng/ml)] were decreased significantly (P < 0.001 for all of them). We did not find
      a significant difference between Graves' disease and toxic nodular goiter for
      hemostatic parameters. In patients with Graves' disease, serum-free T3 levels
      were inversely correlated with TFPI Ag levels (r: -0.57, P < 0.05). In
      conclusion, we found some important differences in the hemostatic parameters
      between the patients with hyperthyroidism and healthy controls. Increased TAFI
      and decreased FV, protein C, protein S, and TFPI in these patients represent a
      potential hypercoagulable and hypofibrinolytic state, which might augment the
      risk for atherosclerotic and atherothrombotic complications. Thus, disturbances
      of the hemostatic system may contribute to the excess mortality due to
      cardiovascular disease seen in patients with hyperthyroidism.

PMID- 19859837
TI  - Variation in gene expression of presenilins-associated rhomboid-like protein and
      mitochondrial function in skeletal muscle of insulin-resistant rats.
AB  - Multiple factors promote insulin resistance. In this study, we evaluated the mRNA
      levels of presenilins-associated rhomboid-like protein (PARL) and mitochondrial
      content and enzyme activity from skeletal muscle isolated from insulin-resistant
      rats. Rats fed a high-fat diet for 35 days developed moderate insulin resistance,
      which was determined by an increase in plasma glucose and insulin concentrations
      following an oral glucose tolerance test. The PARL mRNA level was lower in the
      insulin-resistant rats than in control animals, and is associated with low
      mitochondrial content and reduced mitochondrial enzyme activity in the skeletal
      muscle from the insulin-resistant rats. The results suggest that high-fat-diet
      induced insulin resistance is associated with mitochondrial dysfunction in
      skeletal muscle, and may be the result of the decreased expression of the PARL
      gene, which encodes the protein with functional significance in mitochondria.

PMID- 19859835
TI  - Structural basis of activation of cys-loop receptors: the extracellular
      transmembrane interface as a coupling region.
AB  - Cys-loop receptors mediate rapid transmission throughout the nervous system by
      converting a chemical signal into an electric one. They are pentameric proteins
      with an extracellular domain that carries the transmitter binding sites and a
      transmembrane region that forms the ion pore. Their essential function is to
      couple the binding of the agonist at the extracellular domain to the opening of
      the ion pore. How the structural changes elicited by agonist binding are
      propagated through a distance of 50 A to the gate is therefore central for the
      understanding of the receptor function. A step forward toward the identification
      of the structures involved in gating has been given by the recently elucidated
      high-resolution structures of Cys-loop receptors and related proteins. The
      extracellular-transmembrane interface has attracted attention because it is a
      structural transition zone where beta-sheets from the extracellular domain merge
      with alpha-helices from the transmembrane domain. Within this zone, several
      regions form a network that relays structural changes from the binding site
      toward the pore, and therefore, this interface controls the beginning and
      duration of a synaptic response. In this review, the most recent findings on
      residues and pairwise interactions underlying channel gating are discussed, the
      main focus being on the extracellular-transmembrane interface.

PMID- 19859838
TI  - LMNA gene mutation search in Polish patients: new features of the heterozygous
      Arg482Gln mutation phenotype.
AB  - Mutations of the LMNA gene have been shown to cause an autosomal dominant form of
      insulin resistance with familial partial lipodystrophy (PLD), frequently
      accompanied by diabetes. LMNA mutations are considered to be a rare cause of
      monogenic diabetes; however, they are probably sometimes misdiagnosed as type 2
      diabetes (T2DM). We examined whether skin fold thickness measurements may be an
      effective screening procedure to select individuals with T2DM for molecular
      testing of the LMNA gene. We also aimed to search for mutations in diabetic
      patients with evident clinical features of lipodystrophy. Skin fold measurements
      were performed in 249 not pre-selected T2DM patients. The sum of two trunk skin
      fold measurements divided by the sum of two peripheral was obtained. Men with a
      skin fold ratio above 2.5 and women above 1.5 were selected for further molecular
      analysis of the LMNA gene by direct sequencing. We also examined eight patients
      presenting typical clinical features of lipodystrophy. We selected 16 patients
      with T2DM on the basis of skin fold measurements. LMNA gene sequencing in this
      group revealed no mutation that could be attributable to diabetic phenotype.
      However, in the group of subjects with apparent lipodystrophic phenotype, we
      identified one Arg482Gln mutation. This female, diagnosed with diabetes at the
      age of 51 years, was characterized by insulin resistance but, unlike previously
      reported LMNA Arg48Gln mutation carriers, she was not overweight. The patient
      also presented with chronic kidney disease and pulmonary fibrosis that could
      potentially be a part of the phenotype related to the identified LMNA mutation.
      We did not find the evidence that screening based on skin fold measurements alone
      could be an efficient approach to select T2DM patients for molecular testing of
      the LMNA gene; the presence of features typical for laminopathy seems to be
      required for such testing. A clinical picture related to the LMNA Arg482Gln
      mutation may be more diversified than it was previously considered and include
      low BMI and pulmonary fibrosis.

PMID- 19859839
TI  - Ultrasonographic evaluation of thyroid nodules: comparison of ultrasonographic,
      cytological, and histopathological findings.
AB  - Thyroid ultrasonography (US) and fine needle aspiration biopsy (FNAB) are the
      most important tools in evaluating thyroid nodules. A total of 3,404 nodules in
      2,082 cases referred to our clinic between 2005 and 2008 were analyzed
      retrospectively. Considering US features of nodules, risk factors predicting
      malignancy were: margin irregularity as the most important predictor, hypoechoic
      pattern and microcalcification (Odds ratios: 63.2, 13.3, 7.03, respectively).
      Cytologic results of the patients were as follows: 1,718 (82.5%) benign, 196
      (9.4%) suspicious, 68 (3.3%) nondiagnostic, and 100 (4.8%) malignant. In
      histopathologic examination, we determined a malignancy rate of 7.59% (158/2082).
      We calculated the sensitivity of FNAB as 89.16%, specificity as 98.77%, positive
      predictive value as 96.10%, negative predictive value as 96.39%, and accuracy as
      96.32%. In cytologic examination, the malignancy rate of subcentimetric (<=1 cm)
      nodules was higher than supracentimetric (>1 cm) nodules (5.1% vs. 1.5%, P =
      0.001). In postoperative histopathologic examination, although the malignancy
      rate of subcentimetric nodules was higher than that of supracentimetric nodules,
      the difference was statistically insignificant (5.5%, 4.4%, respectively; P >
      0.05). Cytologically diagnosed malignancy was detected in 4.5% of patients with
      multiple nodules, while it was present in 6% of patients with solitary nodule
      indicating no significant difference. However, postoperative histopathologic
      examination revealed a significantly higher malignancy rate in patients with
      solitary nodule compared to in patients with multiple nodules (11.7%, 6.5%;
      respectively, P < 0.001). The malignancy rate of patients operated for suspicious
      cytology was found to be 46.15%; for nondiagnostic cytology, it was 64.29%. In
      conclusion, ultrasonographically, hypoechoic pattern, microcalcification and
      margin irregularity of thyroid nodules are important features in determining the
      malignancy risk. The nodule size alone still remains inadequate to exclude
      malignancy risk.

PMID- 19859840
TI  - Association of the common rs9939609 variant of FTO gene with polycystic ovary
      syndrome in Chinese women.
AB  - Variations in the fat mass and obesity-associated (FTO) gene have recently been
      associated with obesity and type 2 diabetes mellitus among different ethnic
      populations. Given that the phenotype of polycystic ovary syndrome (PCOS)
      overlaps with obesity and type 2 diabetes, we hypothesize that the common
      rs9939609 variant of FTO gene is related to PCOS susceptibility. We performed a
      case-control association study on 215 women with PCOS, using 227 healthy women as
      the control. We examined the association between rs9939609 variant and PCOS
      susceptibility, as well as between PCOS and obesity-related parameters in Chinese
      women. We observed significant differences in the allelic and genotypic
      distributions between PCOS patients and the control group. The A allele was
      significantly more frequent among PCOS patients than in the control population
      (15.1% vs. 9.9%; A allele vs. T allele, OR = 1.62, P = 0.019). The A allele
      carrier genotype (AA and AT) frequencies were also significantly greater in PCOS
      patients than in the controls (28% vs. 19%; AT and TT vs. TT genotype, OR = 1.61,
      P = 0.035). In logistic regression, the strength of this association was
      attenuated after adjustment for body mass index (BMI) (A allele vs. T allele, OR
      = 1.39, P = 0.286; AT and TT genotypes vs. TT genotype, OR = 1.40, P = 0.312).
      However, we did not find any significant associations of rs9939609 variant with
      obesity-related traits. In conclusions, the rs9939609 variant in the FTO gene is
      associated with PCOS susceptibility in the Chinese population, probably because
      of its effect on BMI.

PMID- 19859841
TI  - Chronic MCH infusion causes a decrease in energy expenditure and body
      temperature, and an increase in serum IGF-1 levels in mice.
AB  - Melanin concentrating hormone (MCH) is an orexigenic peptide secreted from the
      lateral hypothalamus. Various observations suggest a role for MCH in energy
      expenditure in transgenic mice; however, the influence of MCH on energy
      expenditure and body temperature in WT mice was inadequately studied. Therefore,
      our first goal was to characterize the influence of chronic intracerebroventrical
      MCH infusion on energy homeostasis in mice. Our second goal was to explore the
      effect of MCH on the GH-insulin like growth factor 1 (IGF-1) axis in vivo. We
      have recently published that MCH directly increased GH-secretion from pituitary
      cells in vitro, suggesting that MCH may exert part of its effects on energy
      balance via direct pituitary hormone regulation. Mice were centrally infused with
      MCH for 14 days, resulting in a significant increase in food intake, body weight,
      fat mass and plasma IGF-1 levels, while decreasing body temperature and energy
      expenditure. Our data emphasize the role of MCH as a key regulator of energy
      homeostasis by means of appetite regulation, regulation of energy expenditure,
      and an integrator of energy balance with the neuroendocrine system regulating
      pituitary hormone secretion. They also support the notion that MCH may have a
      physiologic role in GH regulation that may, in turn, contribute to its effect on
      body weight.

PMID- 19859842
TI  - Carcinoid tumor of the thymus associated with Cushing's syndrome and dysgeusia:
      case report and review of the literature.
AB  - A 30-year-old man was hospitalized with edema, polyuria, and abnormalities in
      taste. ACTH and cortisol levels at admission were markedly elevated, even after
      attempted suppression with 8 mg dexamethasone. A thoracic-abdominal CT revealed
      an anterior mediastinal lesion and hyperplasia of both adrenal glands. After
      excision of the mediastinal mass, which confirmed the presence of a carcinoid
      thymic tumor, the patient became totally asymptomatic, with normal ACTH and
      cortisol levels. A carcinoid thymic tumor has a poor prognosis, especially when
      it is associated with Cushing's syndrome. Most patients will present recidivism
      or metastasis within 5 years after surgery. However, the low number of cases
      available for analysis makes it difficult to establish optimum therapeutic
      approaches.

PMID- 19859843
TI  - Primary small cell carcinoma of the pleura: a case report with
      immunohistochemical and molecular genetic analyses of KIT and PDGFRA genes.
AB  - An extremely rare case of primary small cell carcinoma of the pleura with an
      emphasis on KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes
      is reported here. A 67-year-old man underwent left testicular orchiectomy because
      of a testicular tumor. The tumor was immunohistochemically shown to be diffuse
      large B-cell lymphoma. The patient was treated with chemotherapy and radiation
      and followed up in our hospital. Eight years after the orchiectomy, the patient
      (75 years old) developed left pleural tumor and pleural effusion, and a biopsy
      was performed. The biopsy revealed a medullary malignant tumor consisting of
      small round and spindle cells. The following three possibilities were considered:
      recurrent lymphoma, mesothelioma, and small cell carcinoma.
      Immunohistochemically, the tumor cells were positive for cytokeratin,
      synaptophysin, CD56, KIT, and PDGFRA, but negative for CEA, cytokeratin 5/6,
      neuron-specific enolase, chromogranin, CD45, CD3, CD20, CD45RO, CD15, CD30,
      calretinin, WT-1, B72.3, D2-40, and TTF-1. Therefore, a diagnosis of pleural
      small cell carcinoma was made. A molecular genetic analysis using PCR-direct
      sequencing identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA
      (exons 12 and 18) genes. The patient was treated with chemotherapy (cisplatin)
      and radiation (50 Gray). The present case is the first reported case of primary
      small cell carcinoma of the pleura with an examination of KIT and PDGFRA
      expressions and KIT and PDGFRA gene mutations.

PMID- 19859844
TI  - Cell cycle inhibition and apoptosis induced by curcumin in Ewing sarcoma cell
      line SK-NEP-1.
AB  - Curcumin is a naturally occurring polyphenolic compound found in the turmeric,
      which is used as food additive in Indian cooking and as a therapeutic agent in
      traditional Indian medicine. Curcumin is currently under investigation as a
      chemotherapeutic and chemopreventive agent in adult cancer models at both pre
      clinical and clinical levels. In this preliminary study, we show that curcumin is
      effective in causing cell cycle arrest, inducing apoptosis, and suppressing
      colony formation in the Ewing sarcoma cell line SK-NEP-1. Curcumin causes
      upregulation of cleaved caspase 3 and downregulation of phospho-Akt, producing
      apoptosis in Ewing sarcoma cells at an inhibitory concentration 50% (IC50) of
      approximately 4 MUM. Our findings indicate a need for further evaluation of
      curcumin in chemotherapy and chemoprevention of Ewing sarcoma.

PMID- 19859847
TI  - The importance of the repressive coping style: findings from 30 years of
      research.
AB  - During the last three decades there has been substantial research exploring the
      repressive coping style as defined by Weinberger, Schwartz, and Davidson. As
      "repressors," who score low on trait anxiety and high on defensiveness, account
      for up to 50% of certain populations, they are an essential group for
      psychologists to study. However, there are methodological issues in identifying
      repressors as well as considerable evidence that repressors avoid negative self
      relevant information. Possible methods of addressing these difficulties are
      discussed in this review. Importantly, there is a body of evidence linking
      repressive coping and poor physical health, including heart disease and cancer.
      However, some preliminary findings suggest that repressors compared to non
      repressors may be better at health behaviors that they perceive as under their
      personal control. This needs more extensive investigation as such behaviors are
      only one aspect of health and other factors may contribute to repressors' poor
      physical health. Possible future directions of research are discussed including:
      the need for systematic empirical research of a new theory of repressive coping-
      the Vigilance-Avoidance Theory--more longitudinal health studies, and an in-depth
      exploration of the physiological mechanisms which may underlie repressive coping.

PMID- 19859848
TI  - Unsteady state flow and stagnation in distribution systems affect the biological
      stability of drinking water.
AB  - The effects of water stagnation and flushing on the biological stability of
      drinking water were studied by promoting the formation of biofilms under
      continuous flow (turbulent or laminar) and subsequently subjecting them to
      unsteady hydraulic situations. Independently of the flow regime under which the
      biofilm was formed, stagnation promoted bacterial accumulation, either in
      attached or suspended form, which were carried away in higher numbers when flow
      was re-started, thereby compromising its biological quality. In all cases,
      Betaproteobacteria was the dominant phylogenetic group, although Gamma and Alpha
      subclasses were also present. These results suggest that special attention should
      be given to the biological quality of drinking water where consumption is
      subjected to strongly variable demands such as in seasonal hotels, week-end
      houses or dental clinics after week-ends as abnormal changes may have occurred in
      the microbiological parameters. Moreover, this study showed that the cultivable
      bacterial numbers are not related to those of total bacteria and, thus, should
      not be the basis for the routine tests of bacteriological control in these
      systems.

PMID- 19859849
TI  - Individual growth curve modeling of specific risk factors and memory in youth
      with type 1 diabetes: an accelerated longitudinal design.
AB  - OBJECTIVE: To examine if diabetes risk factors disrupt memory score trajectories
      in youth with T1D over three years with a powerful accelerated longitudinal
      method and individual growth curve modeling. METHODS: Participants aged 9-17
      completed memory measures at study enrollment and two years later. RESULTS:
      Poorer metabolic control over the course of the study related to a significant
      decrease in visual memory scores. Compared to baseline, these youth scored 1.99
      points lower at follow-up. Generally appropriate developmental gains were made in
      memory trajectories and girls' visual and verbal memory improved more than boys.
      No significant effects of disease duration, age of onset, or severe hypoglycemia
      were found on visual or verbal memory over three years time. CONCLUSIONS: Of the
      risk factors studied, only poorer metabolic control had a significant impact upon
      visual memory after three years. Verbal memory was unaffected. However, given
      that level of metabolic control tends to remain relatively consistent over time,
      the effect of continued poorer metabolic control on memory should be monitored.

PMID- 19859851
TI  - Northern Baja California Indian women's concepts of illness and healing:
      Implications for public health and clinical practitioners.
AB  - Lay health care workers (promotores) interviewed 313 female members of remote
      Indian groups in northern Baja California, Mexico regarding: (1) common childhood
      and adult illnesses and endorsement of 'traditional' and modern therapies; (2)
      illness causation beliefs and knowledge of biomedical principles; and (3) the
      relation of ethnic identity with concepts of effective biomedical and non
      biomedical therapy. The most common illnesses/symptoms reported in adults were
      diabetes, hypertension, high cholesterol, cold/flu, diarrhoea, low/variable blood
      pressure and arthritis; and in children, cold/flu, diarrhoea, bronchitis, cough,
      fever, empacho and dehydration. Of 285 informants, more reported at least one
      childhood disorder than who reported at least one adult disorder was most helped
      by traditional therapy [83 (29.1%) versus 44 (15.4%); P<0.0001] and both
      therapies [81 (28.4%) versus 42 (14.7%); P<0.001]. They reported eight
      naturalistic and two personalistic illness causes and manifested variable
      biomedical knowledge. Indian or mixed Indian/Mexican ethnic self-identity
      predominated, and Indian identity was unrelated to endorsement of traditional
      therapy. The 'biocultural synthesis' is a useful theoretical framework for
      viewing the findings. The Indians' pluralistic concepts have important
      implications for public health care workers and biomedical practitioners.

PMID- 19859852
TI  - Intact first- and second-order implicit sequence learning in secondary-school
      aged children with developmental dyslexia.
AB  - We examined the influence of task complexity on implicit sequence learning in
      secondary-school-aged children with developmental dyslexia (DD). This was done to
      determine whether automatization problems in reading extend to the automatization
      of all skill and depend on the complexity of the to-be-learned skill. A total of
      28 dyslexic children between 12 and 15 years and 28 matched control children
      carried out two serial reaction time tasks using a first-order conditional (FOC)
      and second-order conditional (SOC) sequence. In both tasks, children incidentally
      learned a sequence of hidden target positions, but whereas FOC sequence learning
      could be based on knowledge about the immediate preceding position, SOC sequence
      learning required more complex knowledge about the previous two positions. The
      results demonstrated that sequence learning was highly comparable in dyslexic and
      control children, regardless of the sequence complexity. This shows that implicit
      sequence learning, as manifested in the present study, is maintained in DD and is
      unrelated to task complexity. We suggest that previous reports of sequence
      learning deficits in DD can be accounted for by attenuated explicit sequence
      learning, possibly related to malfunctions in prefrontal processing. The present
      findings indicate that deficits in skill learning and automatization in DD are
      not general in nature, but task dependent.

PMID- 19859853
TI  - Does gender influence cognitive outcome after traumatic brain injury?
AB  - The aim of this study was to determine whether males and females differ in post
      acute cognitive outcome following traumatic brain injury (TBI). Performances of
      83 men and 75 women with mild to severe TBI were compared on measures of
      cognitive functions typically impacted by TBI (i.e., processing speed, executive
      functioning, and memory). Participants completed selected subtests of the
      Cambridge Neuropsychological Test Automated Battery (CANTAB). Among the
      participants with mild TBI, women scored significantly higher than men on a test
      of visual memory. There were no other significant gender differences in cognitive
      outcomes. These findings overall suggest that cognitive outcome after TBI does
      not differ according to gender, with the possible exception of memory
      functioning. Further research is needed to replicate this finding and determine
      which moderating variables may impact on the relationship between gender and
      cognitive outcome after TBI.

PMID- 19859854
TI  - Sensitivity of the test of memory and learning to attention and memory deficits
      in children with ADHD.
AB  - Children with attention deficit hyperactivity disorder (ADHD) exhibit a number of
      cognitive deficits. The current study compared patterns of attention, learning,
      and memory impairment on the Test of Memory and Learning (TOMAL) between 80
      children with ADHD and 80 normal comparisons who were matched for age and gender.
      Results demonstrated that children with ADHD performed significantly worse than
      matched controls on the Attention/Concentration Index and the Sequential Recall
      Index. ROC analysis indicated that these two indexes had good classification
      accuracy with AUCs of.76 and.77 respectively. There were also group differences
      on the other index scores except the Associative Recall Index. Factor analysis of
      the ADHD sample extracted five factors, including an Attention factor that
      significantly correlated with performance on nonverbal memory tasks. Significant
      correlations between the TOMAL Index scores and tests of intelligence and
      visuomotor integration supported the convergent and discriminant validity of the
      test. These results provide support for the criterion validity of the TOMAL in
      assessing neurocognitive deficits in children with ADHD.

PMID- 19859855
TI  - MMPI-2 profiles: fibromyalgia patients compared to epileptic and non-epileptic
      seizure patients.
AB  - We compared MMPI-2 profiles of Gulf War veterans with fibromyalgia (FM) to
      epileptic seizure (ES) patients, psychogenic non-epileptic seizure (PNES)
      patients, and Gulf War veteran healthy controls. Both PNES and FM are medically
      unexplained conditions. In previous MMPI-2 research PNES patients were shown to
      have significantly higher Hs and Hy clinical scales than ES patients. In the
      present research the FM group had significantly higher Hs and Hy scale scores
      than both the ES group and the healthy control group. There was no significant
      difference between the FM and PNES Hs scale scores; however, the FM Hy scale
      score was significantly lower than the PNES Hy scale score. Present findings
      indicate a high level of psychological distress in the FM group.

PMID- 19859856
TI  - Advocacy 101: a step beyond complaining. How the individual practitioner can
      become involved and make a difference.
AB  - There are critical issues facing the neuropsychological community, such as
      inadequate reimbursement for services, a lack of familiarity among public policy
      makers regarding the science and practice of neuropsychology, and a lack of
      public policy awareness among professional neuropsychologists. Advocacy for the
      field is the most effective way to undertake positive change. Currently, a
      minority of psychological professionals actively engages in an advocacy process,
      while the majority is not involved, or is involved periodically or passively.
      With weak advocacy our field risks slower development in key areas, and without
      strong and constant advocacy we risk losing ground previously gained. The purpose
      of this article, and those that follow in this special issue of The Clinical
      Neuropsychologist, is to: (1) convey the importance of advocacy, (2) address and
      dispel unfounded mental obstacles that inhibit involvement in advocating for the
      specialty, and (3) aid neuropsychologists in preparing to join the advocacy
      process. To accomplish this, we acquaint readers with the advocacy process,
      delineate to practitioners how they can become involved, and encourage
      participation in advocacy.

PMID- 19859857
TI  - A hybrid breath hold and continued respiration-triggered technique for time
      resolved 3D MRI perfusion studies in lung cancer.
AB  - PURPOSE: Assessment of lung cancer perfusion is impaired by respiratory motion.
      Imaging times for contrast agent wash-out studies often exceed breath hold
      capabilities, and respiration triggering reduces temporal resolution. Temporally
      resolved volume acquisition of entire tumors is required to assess heterogeneity.
      Therefore, we developed and evaluated an MR measurement technique that exceeds a
      single breath hold, and provides a variable temporal resolution during
      acquisition while suspending breath-dependent motion. MATERIALS AND METHODS: 20
      patients with suspected lung cancer were subjected to perfusion studies using a
      spoiled 3D gradient echo sequence after bolus injection of 0.07 mmol/kg body
      weight of Gd-DTPA. 10 acquisitions in expiratory breath hold were followed by 50
      navigator-triggered acquisitions under free breathing. Post-processing allowed
      for co-registration of the 3D data sets. An ROI-based visualization of the signal
      time curves was performed. RESULTS: In all cases motion-suspended, time-resolved
      volume data sets (40 x 33 x 10 cm(3), voxel size: 2.1 x 2.1 x 5.0 mm(3)) were
      generated with a variable, initially high temporal resolution (2.25 sec) that was
      synchronized with the breath pattern and covered up to 8 1/2 min. In 7 / 20 cases
      a remaining offset could be reduced by rigid co-registration. The tumors showed
      fast wash-in, followed by rapid signal decay (8 / 20) or a plateau. CONCLUSION:
      The feasibility of a perfusion study with hybrid breath hold and navigator
      triggered time-resolved 3D MRI which combines high initial temporal resolution
      during breath hold with a long wash-out period under free breathing was
      demonstrated.

PMID- 19859858
TI  - Computer-aided detection (CAD) and assessment of malignant lesions in the liver
      and lung using a novel PET/CT software tool: initial results.
AB  - PURPOSE: To determine the feasibility of a PET/CT software tool (PET computer
      aided detection: PET-CAD) for automated detection and assessment of pulmonary and
      hepatic lesions. MATERIALS AND METHODS: 20 consecutive patients with colorectal
      liver metastases and 20 consecutive patients suffering from non-small cell lung
      cancer (NSCLC) were examined with FDG-PET/CT. In a first step the maximum
      standardized uptake values (SUV (max)) of non-tumorous liver and lung tissues
      were determined manually. This value was used as a threshold value for software
      based lesion detection. The number of lesions detected, their SUV (max), and
      their sizes in the x, y, and z-planes, as automatically provided by PET-CAD, were
      compared to visual lesion detection and manual measurements on CT. RESULTS: The
      sensitivity for automated detection was 96 % (86 - 99 %) for colorectal liver
      metastases and 90 % (70 - 99 %) for lung lesions. The positive predictive value
      was 80 % for liver and 68 % for lung lesions. The mean SUV (max) of all lung
      lesions was 9.3 and 8.8 for the liver lesions. When assessed by PET-CAD, the mean
      lesion sizes for liver lesions in the x, y, and z-planes were 4.3 cm, 4.6 cm, and
      4.2 cm compared to 3.5 cm, 3.8 cm, and 3.6 cm for manual measurements. The mean
      lesion sizes of lung lesions were 7.4 cm, 7.7 cm, and 8.4 cm in the x, y, and z
      planes when assessed by PET-CAD compared to 5.8 cm, 6.1 cm, and 7.1 cm when
      measured manually. Using manual assessment, the lesion sizes were significantly
      smaller in all planes (p < 0.005). CONCLUSION: Software tools for automated
      lesion detection and assessment are expected to improve the clinical PET/CT
      workflow. Before implementation in the clinical routine, further improvements to
      the measurement accuracy are required.

PMID- 19859859
TI  - First epidemiological analysis of breast cancer incidence and tumor
      characteristics after implementation of population-based digital mammography
      screening.
AB  - PURPOSE: To epidemiologically evaluate the impact of digital mammography
      screening on incidence rates and tumor characteristics for breast cancer.
      MATERIALS AND METHODS: The first German digital screening units in the clinical
      routine were evaluated during the implementation period by using data from the
      cancer registry to compare the incidence rate of breast cancers and prognostic
      characteristics. 74 % of women aged 50 - 69 within the region of
      Muenster/Coesfeld/Warendorf were invited between 10 / 2005 and 12 / 2007 for
      initial screening; 55 % participated (n = 35 961). RESULTS: In 2002 - 2004 the
      average breast cancer incidence rate (per 100,000) was 297.9. During the
      implementation of screening, the rate rose to 532.9 in 2007. Of the 349 cancers
      detected with screening, 76 % (265 / 349) were invasive compared to 90 % (546 /
      608) of cases not detected with screening during the same period. 37 % (97 / 265)
      of cancers detected in the screening program had a diameter of <or= 10 mm and 75
      % (198 / 265) were node-negative compared to 15 % (79 / 546) and 64 % (322 /
      503), respectively, in cancers detected outside the screening program. The
      distribution of invasive tumor size (pT categories) and the nodal status differed
      with statistical significance between cancers detected in and outside the program
      (p = 0.005 and p = 0.004, respectively). CONCLUSION: Epidemiological data shows
      that the implementation of a population-based screening program led to a relevant
      increase in the age-specific breast cancer incidence rate. The characteristics of
      breast cancers detected in the screening program comply with the requirements of
      the European guidelines and are significantly favorable compared to tumors
      diagnosed outside the program. These findings indicate that digital mammography
      screening fulfills the requirements for an early tumor detection tool.

PMID- 19859860
TI  - Lung nodule assessment in computed tomography: precision of attenuation
      measurement based on computer-aided volumetry.
AB  - PURPOSE: To compare the reproducibility (r) of CT value measurement of pulmonary
      nodules using volumetry software (LungCare, LC) and manual ROIs (mROI). MATERIALS
      AND METHODS: 54 artificial nodules in a chest phantom were scanned three times
      with CT. CT values were measured with LC and mROI. The intrascan-r was assessed
      with three measurements in the first scan, and the interscan-r with measurements
      in three consecutive scans (one observer). Intrascan-r und interobserver-r (two
      obs.) were assessed in the first scan and in contrast-enhanced CT of 51 nodules
      from 15 patients (kernels b50f and b80f). Intrascan-r and interscan-r were
      described as the mean range and interobserver-r as the mean difference of CT
      values. The significance of differences was tested using t-test and sign test.
      RESULTS: Reproducibility was significantly higher for volumetry-based
      measurements in both artificial and patient nodules (range 0.11 vs. 6.16 HU for
      intrascan-r, 2.22 vs. 7.03 HU for interscan-r, difference 0.11 vs. 18.42 HU for
      interobserver-r; patients: 1.78 vs. 13.19 HU (b50f-Kernel) and 1.88 vs. 27.4 HU
      (b80f-Kernel) for intrascan-r, 3.71 vs. 22.43 HU for interobserver-r). Absolute
      CT values differed significantly between convolution kernels (pat./mROI: 29.3
      [b50f] and 151.9 HU [b80f] pat./LC: 5 [b50f] and 147 HU [b80f]). CONCLUSION: The
      reproducibility of volumetry-based measurements of CT values in pulmonary nodules
      is significantly higher and should therefore be recommended, e. g. in dynamic
      chest CT protocols. Reproducibility does not depend on absolute CT values.

PMID- 19859861
TI  - Risk of extravasation after power injection of contrast media via the proximal
      port of multilumen central venous catheters: case report and review of the
      literature.
AB  - PURPOSE: Multilumen central venous catheters (CVCs) are not commonly used for
      power injection. However, in critically ill patients, CVCs-- most of which do not
      have FDA approval for power injection--may be the only available venous access.
      MATERIALS AND METHODS: The pitfalls of multilumen CVCs are illustrated by a case
      report of a patient in whom extravasation of intravenously administered contrast
      medium occurred after power injection in a triple-lumen CVC using the lumen with
      the port furthest from the catheter tip. RESULTS: The underlying mechanisms for
      the displacement of the initially correctly placed right subclavian CVC could
      include elevation of both arms of the obese patient or the power injection
      itself. The distances between port openings and catheter tips of various
      commercially available multilumen CVCs are assessed. We examine the possible
      caveats of ECG-guided CVC placement for optimal tip position, discuss technical
      difficulties related to power injection via CVCs, and review commonly used drugs
      that may cause extravasation injury. CONCLUSION: Knowledge of the distances
      between CVC port openings and the catheter tip are essential for safe intravasal
      administration of fluids.

PMID- 19859862
TI  - Interdisciplinary expert consultation via a teleradiology platform--influence on
      therapeutic decision-making and patient referral rates to an academic tertiary
      care center.
AB  - In addition to teleradiological reporting as a nighthawking or a regular service,
      teleradiological communication can be used for interdisciplinary expert
      consultation. We intended to evaluate an interdisciplinary consultation system
      based on a teleradiology platform with regard to its impact on therapeutic
      decision-making, directed patient referrals to an academic tertiary care center
      and the economic benefit for the hospital providing the service. Therefore,
      consultations from five secondary care centers and consecutive admissions to an
      academic tertiary care center were prospectively evaluated over a time period of
      six months. A total of 69 interdisciplinary expert consultations were performed.
      In 54 % of the cases the patients were consecutively referred to the university
      hospital for further treatment. In all acutely life-threatening emergencies (n =
      9), fast and focused treatment by referral to the academic tertiary care center
      was achieved (average time to treat 130 min). The admissions to the academic
      tertiary care center led to improved utilization of its facilities with
      additional revenue of more than 1,000000 euro p. a. An interdisciplinary expert
      consultation via a teleradiology platform enables fast and efficient expert care
      with improved and accelerated patient management and improved utilization of the
      service providing hospital.

PMID- 19859863
TI  - In-vivo quantification of wall motion in cerebral aneurysms from 2D cine phase
      contrast magnetic resonance images.
AB  - PURPOSE: The quantification of wall motion in cerebral aneurysms is of interest
      for the assessment of aneurysmal rupture risk, for providing boundary conditions
      for computational simulations and as a validation tool for theoretical models.
      MATERIALS AND METHODS: 2D cine phase contrast magnetic resonance imaging (2D
      pcMRI) in combination with quantitative magnetic resonance angiography (QMRA) was
      evaluated for measuring wall motion in 7 intracranial aneurysms. In each
      aneurysm, 2 (in one case 3) cross sections, oriented approximately perpendicular
      to each other, were measured. RESULTS: The maximum aneurysmal wall distention
      ranged from 0.16 mm to 1.6 mm (mean 0.67 mm), the maximum aneurysmal wall
      contraction was -1.91 mm to -0.34 mm (mean 0.94 mm), and the average wall
      displacement ranged from 0.04 mm to 0.31 mm (mean 0.15 mm). Statistically
      significant correlations between average wall displacement and the shape of
      inflow curves (p-value < 0.05) were found in 7 of 15 cross sections;
      statistically significant correlations between the displacement of the luminal
      boundary center point and the shape of inflow curves (p-value < 0.05) were found
      in 6 of 15 cross sections. CONCLUSION: 2D pcMRI in combination with QMRA is
      capable of visualizing and quantifying wall motion in cerebral aneurysms.
      However, application of this technique is currently restricted by its limited
      spatial resolution.

PMID- 19859864
TI  - Multidetector CT (MD-CT) in the diagnosis of uncertain open globe injuries.
AB  - PURPOSE: To evaluate the significance of multislice CT for the diagnosis of
      uncertain penetrating globe injuries. MATERIALS AND METHODS: Based on a
      retrospective chart review between 2002 and 2007, we identified 59 patients
      presenting with severe ocular trauma with uncertain rupture of the globe due to
      massive subconjunctival and/or anterior chamber hemorrhage. The IOP (intraocular
      pressure) was within normal range in all patients. High resolution multidetector
      CT (MD-CT) scans (16 slice scans) with axial and coronar reconstructions were
      performed in all patients. The affected eye was examined for signs of penetrating
      injury such as abnormal eye shape, scleral irregularities, lens dislocation or
      intravitreal hemorrhages. Four experienced radiologists read the CT scans
      independently. Beside the diagnosis, the relevant morphological criteria and the
      optimal plane orientation (axial or coronar) were specified. The sensitivity,
      specificity, and negative and positive predictive value were calculated.
      Additionally the interobserver variability was determined by applying the Cohen's
      kappa test. Surgical sclera inspections were performed in all cases as a standard
      of reference. The evaluations of the CT examination were compared with the
      surgery reports. RESULTS: 59 patients were evaluated (42 men, 17 women). The mean
      age was 29 years (range 7 - 91). In 17 patients a rupture of the globe was
      diagnosed during surgery. 12 of these 17 penetrating injuries (70.6 %) were
      classified correctly by MDCT, 5 of the 17 (29.4 %) were not detectable. 42
      patients did not have an open globe injury. 41 of these patients were diagnosed
      correctly negative by MDCT, and one patient was classified false positive. This
      results in a sensitivity of 70 % with a specificity of 98 %. There was high inter
      rater agreement with kappa values between 0.89 - 0.96. Most discrepancies were
      caused by wrong negative findings. The most frequent morphologic criteria for
      open globe injury were the deformation (n = 10) and the volume reduction (n = 7)
      of the globe. These changes were most certain and visible in the axial
      orientation. CONCLUSION: In about one third of all unclear cases with rupture of
      the globe due to severe trauma, CT evaluation failed to correctly diagnose the
      open globe injury, which might lead to a delay in necessary surgical
      intervention. Thus, surgical sclera inspection is always mandatory in such
      unclear trauma cases regardless of the MD-CT results.

PMID- 19859865
TI  - [Assessment of clinical image quality in feline chest radiography with a needle
      image plate (NIP) storage phosphor system--an approach to the evaluation of image
      quality in neonatal radiography].
AB  - PURPOSE: Is the image quality of thoracic radiographs of cats obtained with a
      needle-based storage phosphor (NIP) system superior to conventional (PIP) storage
      phosphor radiography? Is it possible to decrease the mAs by 50 % with the NIP
      system without significant loss of information? MATERIALS AND METHODS: From each
      of the 20 animals, three lateral radiographs were acquired. The assessment of the
      exposure level was based on the generated lgM-values. Images were acquired 1.
      with the NIP system and exposure settings equivalent to an lgM of 1.9, 2. with
      the PIP system and identical settings, and 3. with the NIP system and 50 % of the
      mAs. Six blinded readers used a 5-step scale to assess the reproducibility of
      five anatomical structures and image noise sensation. Data were analysed using
      Visual Grading Characteristics Analysis (VGC). RESULTS: While applying identical
      exposure values the NIP system for all features revealed superior ratings to
      those of the PIP system (AUC (VGC) values ranged from 0.81 for "cardiac
      silhouette" to 0.92 for "trachea"). Even when reducing mAs by 50 % in the NIP
      images all features were rated better compared with the PIP images and original
      settings (AUC (VGC) values ranged from 0.60 for "cardiac silhouette" to 0.74 for
      "trachea" and "caudal thoracic field"). CONCLUSION: The NIP system demonstrates
      clearly better image quality compared to the reference PIP system. A dose
      reduction of 50 % seems to be possible without relevant detraction from image
      quality. The results obtained in the animal model are valid for simulating
      conditions in neonatal radiological practise.

PMID- 19859866
TI  - Blood oxygenation level-dependent MRI of the skeletal muscle during ischemia in
      patients with peripheral arterial occlusive disease.
AB  - PURPOSE: To compare calf muscle Blood Oxygenation Level-Dependent (BOLD) response
      during ischemia in patients suffering from peripheral arterial occlusive disease
      (PAOD) and age-matched non-PAOD subjects. MATERIALS AND METHODS: PAOD patients
      with symptoms of intermittent calf claudication and an age-matched control group
      underwent T 2*-weighted single-shot multi-echo planar imaging on a whole-body MR
      scanner at 1.5 T. The muscle BOLD signal in the calf was acquired during 60 sec
      of baseline and 240 sec of ischemia induced by cuff compression. T 2* time
      courses in four calf muscles were evaluated. RESULTS: Significant differences in
      the mean T 2* values were noted after 150 sec of measurement (p < 0.05). Patients
      with PAOD revealed a significantly reduced BOLD signal decrease compared to an
      age-matched control group. CONCLUSION: Potential cause for this observation may
      be changes in the structure and/or the metabolic turnover of the muscle in PAOD
      patients.

PMID- 19859867
TI  - Development of a permanently controllable rotating biopsy device, part II:
      Competitive in-vitro testing of a cannula-like prototype compared to established
      end-cut and side-notch biopsy devices.
AB  - PURPOSE: To evaluate the quantitative and qualitative efficiency of a permanently
      controllable biopsy-cannula prototype with lancet-like helically bent cutting
      edge for safer biopsy compared to established end-cut and side-notch biopsy
      devices. MATERIALS AND METHODS: Each of the n = 100 specimens per organ and
      system were obtained by the prototype, an end-cut device and a side-notch device
      (18 gauge each) using a bovine liver, kidney and myocardium as the biopsy tissue.
      Quantitatively, the number of fragments, length in mm and weight in mg of the
      specimen were analyzed. Qualitatively, a histopathological analysis was performed
      with respect to tissue fragmentation, crush artifact and adequacy of tissue
      (score per category min. 1 and max 3). To identify significant differences (p <
      0.025), chi-square and Kruskal-Wallis tests were calculated in the statistical
      analysis. RESULTS: For each of the n = 300 specimens, the one-piece fragment/mean
      length/mean weight were n = 232 / 10.34 mm/ 4.86 mg for the prototype, n = 210 /
      12.16 mm/ 5.35 mg for the end-cut system and n = 248 / 11.63 mm/ 4.08 mg for the
      side-notch system. The differences reached a level of significance with p <
      0.001. The mean histopathological score for the prototype/end-cut system/side
      notch system was 5.60 / 5.60 / 5.25 for the liver, 5.65 / 4.65 / 4.60 for the
      kidney and 5.05 / 5.35 / 4.85 for the myocardium. The differences did not reach a
      level of significance for the liver/kidney/myocardium with p = 0.665 /p = 0.186
      /p = 0.436. CONCLUSION: Compared to established core biopsy systems, the biopsy
      cannula prototype offers diagnostically equivalent biopsy specimen quality in an
      in-vitro setting in bovine liver, kidney and myocardium.

PMID- 19859868
TI  - [Non-suicidal self-injury and suicide attempts: grounding of differential
      diagnosis].
AB  - Three criteria for differential diagnosis of non-suicidal self-injury and suicide
      attempts were validated by means of more recent empirical studies. Criteria
      concerning motives (functions), methods of self-injury (medical severity),
      lifetime frequency and lifetime number of episodes were investigated. Literature
      research showed only a few studies concentrated on a direct comparison of non
      suicidal self-injury and suicide attempts. Therefore, studies examing the
      relationship of suicide intent to the relevant features, are considered, too.
      Empirical results concerning motives (functions), methods (medical severity),
      lifetime frequency and number of episodes were compared to the three criteria.
      Except for lifetime frequency, studies support the criteria. However, in the case
      of motives, a more differentiated examination is needed to distinguish between
      non-suicidal self-injury and suicide attempts. To optimize the assessment,
      guidelines should be slightly modified. Because of the phenomenological overlap
      of non-suicidal self-injury and suicide attempts, a dimensional assessment can be
      helpful.

PMID- 19859869
TI  - [Pre-, peri- and postpartal depression].
AB  - INTRODUCTION: Postpartal affective disorders are with a prevalence between 8 %
      and 15 % highly frequent maternal diseases after childbirth. An undetected and
      untreated postpartum depression causes a wide range of negative consequences such
      as risk of a chronic manifestation of a major depression, social retreat,
      limitations in the bonding behavior, and behavioral disorders of the child.
      Therefore, an early detection of pregnant women at risk is warranted. METHODS:
      Within a prospective study (FRAMES: Franconian Maternal Health Evaluation
      Studies), 1,100 pregnant women were interviewed with standardized questionnaires
      at three points of time: Prepartal (U1): from the 30 (th) week of pregnancy
      onwards, 48 - 72 hours (U2) postpartum (pp) und 6 - 8 months pp (U3). 554 women
      were included in the substudy Blue FRAMES, where an additional telephone
      interview at the 10 (th) day pp was conducted with a focus on symptoms relating
      to Baby Blues such as mood instability, irritability and concentration deficits.
      The Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale For
      Depression (HAMD) were used for quantification of depressivity at each point of
      time. RESULTS: EPDS values differed significantly (Friedman Test; chi (2) =
      110.8; df = 2, p < 0,001) between the different examination points (Wilcoxon
      Test; U1 - U2: Z = -11.0; p < 0.001; U1 - U3: Z = -6.6; p < 0.001; U2 - U3: Z = 
      4,5; p < 0,001). Regarding EPDS values, higher values were observed prepartum
      (U1). After a decrease after two to three days postpartum (U2), values increased
      again. However, EPDS values six months postpartum (U3) were still lower than
      prepartum (U1). DISCUSSION: The observed EPDS values postpartum are comparable to
      results of other studies. The higher EPDS values prepartum have a good predictive
      value. There is a great need and possibility for improved prevention of
      postpartal disorders, when appropriately addressed in the prepartum period.

PMID- 19859870
TI  - [Efficient production of transfected human keratinocytes under serum-free and
      feeder layer-free conditions].
AB  - PURPOSE/BACKGROUND: Keratinocyte transplantation after burn injury and in chronic
      wound treatment is a potentially useful method in clinical practice. As transfer
      of keratinocytes is easily monitored and gene expression is controllable by
      topical administration of inductors, keratinocyte cultures are an especially
      interesting medium for gene therapeutic approaches far above of wound healing
      applications. A major obstacle is the standardization of keratinocyte preparation
      and maintenance of pure proliferative cultures for clinical application. The best
      outcomes in previous protocols were obtained using fibroblasts as a feeder layer,
      a requirement for long-term expanded cultures. Cell expansion and a high purity
      of keratinocytes are prerequisites for clinical transfer studies. Here, we
      describe a human keratinocytes preparation method that allows cell proliferation
      and expansion in culture without a feeder layer. MATERIALS AND METHODS: Human
      keratinocytes were prepared from skin biopsies and cultured on untreated plastic
      culture dishes using Waymouth medium the first days followed by a change to a
      commercially available serum-free keratinocyte medium. The cells were
      characterized morphologically followed by transfection. For positive selection,
      transfected cells were selected by the cotransfection system pMACS Kk and
      magnetic cell sorting. RESULTS: Transfection rates were determined by expression
      of GFP vector which were 35%. The usage of magnetic cell sorting resulted in
      positive selection of transfected cells. Positive cells were able to adhere and
      proliferate after the sorting procedure. High viability and expansion of plastic
      adherent keratinocytes was achieved allowing up to 5 passages without signs of
      senescence and the doubling times were 3-5 days. The cells displayed typical
      keratinocyte morphology and immunostaining confirmed high keratinocyte purity.
      The number of contaminating fibroblasts was low. CONCLUSION: Here, we describe an
      efficient and inexpensive method for a standardized human keratinocyte isolation
      without the need of a fibroblast feeder layer. This protocol may facilitate the
      clinical application of cell based therapies in burn injuries or chronic wounds
      using keratinocytes.

PMID- 19859871
TI  - Microstructure and properties of nano-fibrous PCL-b-PLLA scaffolds for cartilage
      tissue engineering.
AB  - Nano-fibrous scaffolds which could potentially mimic the architecture of
      extracellular matrix (ECM) have been considered a good candidate matrix for cell
      delivery in tissue engineering applications. In the present study, a
      semicrystalline diblock copolymer, poly(epsilon-caprolactone)-block-poly(L
      lactide) (PCL-b-PLLA), was synthesized and utilized to fabricate nano-fibrous
      scaffolds via a thermally induced phase separation process. Uniform nano-fibrous
      networks were created by quenching a PCL-b-PLLA/THF homogenous solution to -20
      degrees C or below, followed by further gelation for 2 hours due to the presence
      of PLLA and PCL microcrystals. However, knot-like structures as well as
      continuously smooth pellicles appeared among the nano-fibrous network with
      increasing gelation temperature. DSC analysis indicated that the crystallization
      of PCL segments was interrupted by rigid PLLA segments, resulting in an amorphous
      phase at high gelation temperatures. Combining TIPS (thermally induced phase
      separation) with salt-leaching methods, nano-fibrous architecture and
      interconnected pore structures (144+/-36 mm in diameter) with a high porosity
      were created for in vitro culture of chondrocytes. Specific surface area and
      protein adsorption on the surface of the nano-fibrous scaffold were three times
      higher than on the surface of the solid-walled scaffold. Chondrocytes cultured on
      the nano-fibrous scaffold exhibited a spherical condrocyte-like phenotype and
      secreted more cartilage-like extracellular matrix (ECM) than those cultured on
      the solid-walled scaffold. Moreover, the protein and DNA contents of cells
      cultured on the nano-fibrous scaffold were 1.2-1.4 times higher than those on the
      solid-walled scaffold. Higher expression levels of collagen II and aggrecan mRNA
      were induced on the nano-fibrous scaffold compared to on the solid-walled
      scaffold. These findings demonstrated that scaffolds with a nano-fibrous
      architecture could serve as superior scaffolds for cartilage tissue engineering.

PMID- 19859872
TI  - [Depression in Alzheimer type-dementia: is there any effect on memory
      performance].
AB  - INTRODUCTION: Depression is one of the most common neuropsychiatric disorders in
      Alzheimer's disease (AD). AIM: To evaluate whether depression exacerbates verbal
      and non-verbal memory impairment in early AD patients. SUBJECTS AND METHODS: The
      study compared the performance of 23 patients who received a diagnosis of AD,
      with or without depression, 15 patients with unipolar major depression (UD) and
      20 healthy control subjects (HS) on memory tasks (recall and recognition) for
      words, abstract designs and position. AD patients were stratified into two
      groups, according to the presence or absence of depression, well matched on
      clinical and sociodemographic characteristics. RESULTS: Patients with AD scored
      significantly lower than HS and UD groups on verbal memory measures. However, the
      recognition was the only non-verbal memory measure that discriminated
      significantly between AD and UD groups. The AD groups (with or without
      depression) did not show any significant differences on memory performance.
      CONCLUSIONS: Depression is associated with significant memory impairment in non
      demented patients. The presence of depression did not increase memory impairment
      in AD patients.

PMID- 19859873
TI  - [Deep brain stimulation: 12 years' experience and 150 patients treated with a
      follow-up of over a year].
AB  - INTRODUCTION: Deep brain stimulation (DBS) is a widely accepted clinical
      technique. The main motor symptoms are significantly reduced. The success of the
      technique depends on the experience of the neurosurgeon, neurologist and
      neurophysiologist who carry it out. The presentation of extensive series is
      needed to confirm and further currently held knowledge. AIM: To demonstrate the
      clinical benefits of a long series of patients treated by a single group with a
      minimum follow-up of one year and to report new neurophysiological data. PATIENTS
      AND METHODS: The study examined a total of 250 patients with different diagnoses:
      most of them with Parkinson's disease, tremor and dystonia. The nuclei that were
      chosen were located by magnetic resonance imaging, computerised axial tomography
      and neurophysiological registers. Neurophysiological exclusion criteria, such as
      reflex control of heart rate, sympathetic skin response and auditory startle
      reflex, are employed in order to exclude patients with Parkinson-plus. RESULTS:
      The motor sub-scale (part III) of the Unified Parkinson's Disease Rating Scale
      improves by 64% in the off-medication status with sub-thalamic stimulation at one
      year after surgery. One year after DBS, patients with dystonia show a significant
      decrease on the Burke-Fahn-Marsden dystonia scale. The improvement on the scales
      continues, with a mean descent of 65% in the second year after surgery.
      CONCLUSIONS: DBS is a suitable technique for the treatment of movement disorders.
      The neuronal activity of the sub-thalamus and the internal globus pallidus
      presents its own characteristics that reflect the motor symptoms of the patients.
      Surface electromyography proves to be useful for quantifying the patients'
      improvement.

PMID- 19859874
TI  - [The use of intravenous levetiracetam in a general hospital].
AB  - INTRODUCTION AND AIMS: Although antiepileptic drugs are usually administered
      orally, sometimes they must be given intravenously. Levetiracetam is the only one
      of the new antiepileptic drugs that can be administered intravenously. In this
      study we report on the use of intravenous levetiracetam in a general hospital,
      while also evaluating its effectiveness and safety. PATIENTS AND METHODS: A
      retrospective analysis was conducted of the medical records of all hospital
      admissions that were treated with intravenous levetiracetam between July 2007 and
      May 2008. RESULTS: A total of 53 patients were treated with intravenous
      levetiracetam. Approximately half the patients (47%) had been admitted to
      neurology, followed by neurosurgery (21%) and oncology (9%). The mean age was
      52.2 years (range: 9-87 years) and 40% were females. Seizures were symptomatic in
      81% of cases and the most common aetiologies were strokes (40%) and brain tumours
      (33%). The most frequent presenting symptoms were repeated epileptic seizures
      (47.2%) and epileptic status (26.4%). Overall, control of seizures was achieved
      in 87% of patients. No severe side-effects that could be attributed to
      levetiracetam therapy were detected. CONCLUSIONS: Intravenous levetiracetam seems
      to be an effective, safe antiepileptic drug in hospitalised patients, and
      especially so in those who present an associated comorbidity and/or who are on
      multiple drug therapy.

PMID- 19859875
TI  - [Periodontal disease as an early clinical sign of cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)].
AB  - INTRODUCTION: The clinical signs of cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) are expressed mainly in
      the nervous system and recently reports also situate them in the retina. AIM: To
      determine the prevalence and risk of periodontal disease in subjects from
      families with a history of CADASIL mutation in the department of Antioquia,
      Colombia. SUBJECTS AND METHODS: A cross-sectional study was conducted, with
      subjects being assigned to the CADASIL group or a control group according to
      genotyping for the R1031C and C455R mutation in Notch3. Each participant
      voluntarily signed the informed consent document and was submitted to
      neurological, neuropsychological and periodontal evaluation. RESULTS: No
      significant differences were found between the two groups according to age, sex,
      schooling, tobacco smoking, cognitive status, functional status and the presence
      of natural teeth. The frequency of soft plaque, gingivitis and periodontal
      disease was significantly higher in the group of carriers of the CADASIL mutation
      than in the control group. The CADASIL group had six times more risk of having
      soft plaque above or equal to 20% than the control group. Prevalence of
      gingivitis above or equal to 10% was observed in all the members of the CADASIL
      group. The people in the CADASIL group had five times more risk of suffering
      periodontal disease than the control group. CONCLUSIONS: Carriers of the CADASIL
      mutation displayed a higher prevalence and risk of periodontal disease.

PMID- 19859876
TI  - [Delays in the arrival of patients with subarachnoid haemorrhage at a tertiary
      hospital].
AB  - INTRODUCTION: Patients with subarachnoid haemorrhage should be referred to a
      tertiary hospital as early as possible. The aim of this research was to study how
      long these patients take to reach a tertiary care centre in Havana. PATIENTS AND
      METHODS: We conducted a prospective study of patients with subarachnoid
      haemorrhage who were admitted to the Stroke Unit at the Hospital Hermanos
      Ameijeiras between January 2005 and December 2007. The time of arrival at the
      hospital was determined and a comparison was carried out between patients who
      arrived after 72 hours and those who reached the hospital sooner. RESULTS: The
      sample studied comprised 94 patients. Only 34 (36%) arrived during the first
      three days, whereas 13 (13.8%) reached the hospital within the first 24 hours.
      None of the sociodemographic and clinical variables that were studied was
      associated with early remission. The length of time spent in hospital by patients
      admitted during the first 72 hours was 14.9 days, while in the other cases it was
      17.57 days (p = 0.248). The greatest impact on early remission to the tertiary
      centre was on the outcome at discharge on the Rankin scale, which was lower in
      those who arrived early compared to the rest of the cases (p = 0.05); the same
      was true of mortality, which was 5.9% in those who arrived within the first 72
      hours versus 11.7% in the others (p = 0.04). CONCLUSIONS: Only a third of the
      cases reached hospital during the first 72 hours and this group had a more
      favourable course.

PMID- 19859877
TI  - [Intracranial hypertension associated with cerebral venous sinus thrombosis and
      mastoiditis. Two paediatric case reports].
AB  - INTRODUCTION: Cerebral venous sinus thrombosis is a rare condition that is
      generally associated with acute processes, one of the most important being
      mastoiditis. Associated prothrombotic disorders can be detected in approximately
      half of all cases, regardless of the aetiology. Patients usually present clinical
      symptoms like headache, convulsions and diminished level of awareness, this
      latter factor being linked to a poor prognosis. CASE REPORTS: We report the cases
      of two paediatric patients with a clinical picture of intracranial hypertension
      within a context of mastoiditis as a complication of an acute ear infection, in
      whom cerebral venous sinus thrombosis was identified. Both patients were treated
      with lumbar punctures to evacuate cerebrospinal fluid and diuretic therapy.
      Anticoagulant therapy was added in the case of the second patient. Nevertheless,
      because of the persistence of the symptoms of intracranial hypertension, a
      ventriculoperitoneal shunt had to be performed in this patient. CONCLUSIONS: The
      preferred diagnostic method is magnetic resonance imaging with venography,
      although in an emergency computerised tomography can help reach a diagnosis in a
      third of cases. In addition to treating the symptoms, anticoagulation is also
      accepted (degree of evidence 1B) to prevent further progression.

PMID- 19859878
TI  - [Acute transverse myelitis: a clinical review and algorithm for diagnostic
      intervention].
AB  - INTRODUCTION: Under the term of acute transverse myelitis (ATM), there are
      included a heterogeneous group of diseases, with the nexus common to produce an
      inflammatory focal injury of the spinal cord, of acute form. In order to try to
      group all the etiologies that can provoke this affectation, it is nowadays tried
      to define several groups of pathologies with a common nexus: those ATM associated
      to some process, or at least predisposed of the ATM, like are certain infections,
      immunological systemic and/or multifocal processes, and inclusive tumors, but
      when we did not get to know this triggering factor, then calling them idiopathic
      ATM. AIM: To know the different classes from existing ATM, creating an algorithm
      diagnosis that helps to this classification of ordinate form, simplifying the
      work to the clinicians that faces a ATM, exposing its differential diagnosis,
      prognosis and possible treatment. DEVELOPMENT: For it we consulted the last
      guides and works published related to the ATM, mainly from the diagnostic and
      therapeutic point of view. CONCLUSIONS: Our knowledge of the ATM is being
      constantly modified with the coming of new diagnostic techniques and theories
      that try to explain their origin, probably immunological. Unfortunately, the
      treatment, and therefore the prognosis, has not varied in the same proportion to
      the knowledge that we are acquiring in the other areas. Without a doubt, it is a
      way important to walk, but the next future can teach to us more on this disease.

PMID- 19859879
TI  - [Genetics components in patients with temporal lobe epilepsy].
AB  - INTRODUCTION: Epilepsy is one of the major neurological disorders characterized
      by spontaneous and recurrent seizures. Traditionally temporal lobe epilepsy (TLE)
      was considered as a multifactorial syndrome due to environmental factors.
      Advances in molecular biology have facilitated the detection of many genetic
      alterations that may have a pathogenic effect in ELT. Recently, many authors show
      evidence about the existence of genetic components as the source of some types of
      ELT. DEVELOPMENT: This review aims to provide an overview of mutations and
      polymorphisms associated with temporal lobe epilepsy, which have been described
      in scientific literature and its contribution to the pathophysiology of
      epileptogenesis. We have reviewed the following genes; LGI1, PDYN (prodynorphin),
      interleucine 1beta, PRPN (prion protein), ApoE (apolipoprotein E), GABBR1, SCN1A,
      SCN1B, KCNA1, KCND2. CONCLUSION: The ELT is a complex disease and its development
      could depend on either genetics factors or other factors. Functional studies are
      necessary in order to correlate its molecular basis and their development.

PMID- 19859880
TI  - [Lumbosacral arachnoiditis secondary to a lumboperitoneal shunt].

PMID- 19859882
TI  - [Carpal tunnel release: avoiding complications].

PMID- 19859883
TI  - [Fifteen years history of Parkinson's disease in Spain. The dark years].

PMID- 19859884
TI  - [Orally disintegrating donepezil: are the main caregivers of patients with
      Alzheimer's disease more satisfied with this formulation of donepezil than with
      the traditional one?].
AB  - AIM: To know whether caregivers of Alzheimer's disease (AD) patients on donepezil
      treatment are more satisfied with the orally disintegrating tablet (ODT)
      formulation than with the film-coated tablets. PATIENTS AND METHODS: Multicenter,
      cross-sectional study of patients with probably AD by DSM-IV or NINCDS-ADRDA
      criteria, on monotherapy with donepezil, ODT or film-coated tablets. Satisfaction
      with treatment was assessed by the caregiver self-administered generic Treatment
      Satisfaction with Medicines Questionnaire (SATMED-Q) -range: 0, no satisfaction,
      to 100, maximal satisfaction-, total and in six dimensions: undesirable effects,
      efficacy, medical care, medication ease and convenience, medication impact on
      daily activities, and overall satisfaction. RESULTS: 546 patients were enrolled
      (9,6% institutionalized); 64,8% women; 78,2 +/- 6,5 years of age; disease
      evolution of 22.5 +/- 24.6 months, Minimental State Examination (MMSE) mean
      score: 18,5 +/- 5; 67.9% on film-coated tablets and 32.1% on ODT. After adjusting
      by MMSE and time of treatment, caregivers of patients on ODT showed significantly
      higher SATMED-Q total score (74.5 +/- 11.8 vs. 70.4 +/- 12.3; p lower than
      0.0004) and medication ease and convenience (84.9 +/- 16.4 vs. 79.8 +/- 17.6; p =
      0.0059), impact of medication on daily activities (50.2 +/- 22.8 vs. 43.7 +/-
      25.5; p = 0.0006) and satisfaction with medical care (79.4 +/- 19.5 vs. 75.6 +/-
      21.8; p = 0.04894) scores. 91.6% of caregivers of patients on ODT (versus 82.9%
      of those on film-coated tablets; p = 0.023) stated that taking the medication was
      easy for their relatives. CONCLUSIONS: Results show that caregivers of AD
      patients on donepezil treatment are more satisfied with ODT versus film-coated
      tablets, especially due to its better ease of use.

PMID- 19859885
TI  - [Mucopolysaccharidosis: 20-year enzymatic diagnosis in Cuba].
AB  - INTRODUCTION: Mucopolysaccharidoses (MPS), which belong to the family of inborn
      errors of metabolism, are characterised by their severe clinical manifestations
      (skeletal, neurological and visceral) and a chronic, progressive course leading
      to death at early stages of life. AIM. To accomplish an enzymatic diagnosis and
      characterise MPS within the Cuban population. SUBJECTS AND METHODS: A total of
      664 patients with a clinical suspicion of some type of MPS were referred to the
      Institute of Neurology and Neurosurgery in Havana in order to determine a
      possible enzymatic deficiency and to classify the type of MPS involved in each
      case. Enzymatic determinations of alpha-L-iduronidasa, alpha-N
      acetylglucosaminidase, beta-galactosidase, arylsulphatase B and beta
      glucuronidase were performed in leukocyte homogenate for MPS I, IIIB, IVB, VI and
      VII, respectively, in patients, parents and controls. RESULTS. In all, 42 cases
      of MPS were diagnosed: MPS I (62%, n = 26), MPS VI (29%, n = 12), MPS IIIB (7%, n
      = 3) and MPS IVB (2%, n = 1). No patients with MPS VII were identified. The
      patients diagnosed with MPS were of both sexes and ages ranged between 4 months
      and 10 years. The specific activity of the enzymes that were studied was
      deficient in patients with respect to parents and controls. The percentage of
      activity was lower in patients compared to parents. CONCLUSIONS: These studies
      made it possible to evaluate the enzymatic deficiencies and to establish the
      diagnosis of MPS I, MPS IIIB, MPS IVB, MPS VI and MPS VII in the Cuban
      population.

PMID- 19859886
TI  - [Monitoring neurodevelopment in children born as a result of using assisted
      reproduction techniques].
AB  - INTRODUCTION: In recent years a number of publications have reported a higher
      incidence of congenital defects or chromosome abnormalities linked to
      conventional in vitro fertilisation (IVF), and some other publications have
      suggested that intracytoplasmic sperm injection (ICSI) may have a negative
      influence on neurodevelopment. AIM. To determine whether there were any
      differences in the medical development and the neurodevelopment of children
      conceived using conventional IVF techniques and those conceived using ICSI
      techniques. SUBJECTS AND METHODS: Our sample consisted of 17 babies born after
      IVF (nine males and eight females) and 40 infants born after ICSI (23 males and
      17 females). All of them were the result of pregnancies induced by IVF and ICSI
      achieved in the assisted reproduction service at our hospital and followed up by
      the same team of obstetricians and specialists in maternal-foetal medicine. At
      the chronological age of 24 months all the patients were submitted to a
      paediatric examination and a neuropsychological examination. The examination was
      performed in one single session. Neurodevelopment was evaluated specifically by
      means of the Bayley scales of infant development. RESULTS AND CONCLUSIONS: The
      health and neurodevelopment of infants from conventional IVF and from ICSI in our
      study were similar to those of the general population at the age of two years.
      ICSI proved to be as safe as conventional IVF as regards the children's medical
      and cognitive progression.

PMID- 19859887
TI  - [Diagnosis of valve dysfunction in the paediatric age: the predictive value of
      the clinical signs and symptoms].
AB  - INTRODUCTION: Cerebrospinal fluid shunt valves are the preferred treatment in
      many cases of childhood hydrocephalus. Cerebrospinal fluid shunt valve
      dysfunctions usually present in an unspecific manner, which delays their
      diagnosis and, consequently, can increase the morbidity and mortality rates in
      these patients. AIM: To determine the signs and symptoms that are most suggestive
      of valve dysfunction in the childhood population. PATIENTS AND METHODS: We
      conducted a retrospective study of the reports of patients who visited the
      emergency department of a tertiary care paediatric hospital with a clinical
      picture that suggested valve dysfunction. In each case the clinical
      manifestations were determined, and also whether there had been a diagnosis of
      valve dysfunction or not. A univariate analysis and later a logistic regression
      study were performed. RESULTS: In all, 183 visits were included. Valve
      dysfunction was confirmed in 28.5% of them. The most frequent complication was
      obstruction of the proximal drainage catheter. The univariate analysis showed a
      significant relation between the presence of irritability, sleepiness, abdominal
      pain, paresis of the cranial nerves and increased perimeter of the skull, and the
      existence of valve dysfunction. The logistic regression analysis revealed that
      sleepiness, irritability and abdominal pain could predict valve dysfunction.
      CONCLUSIONS: Sleepiness and irritability are the clinical manifestations that
      best predict valve dysfunction, which means that they are almost undoubtedly
      candidates for an urgent neuroimaging study. In most cases the abdominal pain is
      related to abdominal pseudocysts. Headaches, vomiting and a high temperature are
      less predictive of valve dysfunction.

PMID- 19859888
TI  - [Contiguous gene deletion syndrome in Xp21: an unusual form of presentation].
AB  - INTRODUCTION: We report a case of an infant where the association of Duchenne's
      muscular dystrophy (DMD) and pseudohypertriglyceridaemia led to the diagnosis of
      contiguous gene deletion syndrome in Xp21. CASE REPORT: A 7-month-old male infant
      who was referred due to psychomotor retardation. The examination revealed
      pronounced axial hypotonia. Lab findings showed high levels of muscular enzymes
      with creatine phosphokinase levels of 12,829 IU/L, together with high blood
      levels of triglycerides. Electromyogram findings were consistent with myopathic
      compromise. The genetic study for dystrophinopathies revealed the existence of a
      deletion in the dystrophin gene. Further lab findings identified high glycerol
      concentrations both in blood and in urine that were compatible with a glycerol
      kinase deficiency. The genetic study confirmed the existence of a deletion in
      Xp21 of the genes responsible for DMD, the glycerol kinase deficiency, the
      congenital adrenal hypoplasia (gene DAX1) and mental retardation (gene IL1RAPL1).
      CONCLUSIONS: In infants and small children with myopathic compromise, increased
      levels of creatine phosphokinase and pseudohypertriglyceridaemia it is essential
      to take into account contiguous gene deletion syndrome in Xp21 to be able to
      prevent and treat the metabolic complications arising from adrenal hypoplasia.

PMID- 19859889
TI  - [Tropical causes of epilepsy].
AB  - INTRODUCTION: Eighty-five percent of all epileptics live in tropical regions.
      Prenatal risk factors, traumatic brain injuries and different parasitic
      infestations of the central nervous system (CNS) are the reasons behind the high
      prevalence of epilepsy. This work reviews the main parasitic infestations causing
      epilepsy in the tropics. DEVELOPMENT: Neurocysticercosis is the main cause of
      focal epilepsy in early adulthood in endemic areas (30-50%). All the phases of
      cysticerci (viable, transitional and calcified) are associated with epileptic
      seizures. Anti-cysticercus treatment helps get rid of cysticerci faster and
      reduces the risk of recurrence of seizures in patients with viable cysts.
      Symptomatic epilepsy can be the first manifestation of neuroschistosomiasis in
      patients without any systemic symptoms. The pseudotumoral form can trigger
      seizures secondary to the presence of granulomas and oedemas in the cerebral
      cortex. The eggs of Schistosoma japonicum are smaller, reach the CNS more easily
      and trigger epileptic seizures more frequently. Toxocariasis and sparganosis are
      other parasitic infestations that can give rise to symptomatic seizures. The risk
      factors for suffering chronic epilepsy after cerebral malaria are a positive
      familial history of epilepsy and a history of episodes of fever and cerebral
      malaria that began with coma or which progressed with multiple, prolonged
      epileptic seizures. About 20% of patients with cerebral infarction secondary to
      Chagas disease present late vascular epilepsy as a complication. CONCLUSIONS:
      Very few studies have been conducted to examine the prognosis, risk of recurrence
      and modification of the natural course of seizures associated with tropical
      parasitic infestations, except for the case of neurocysticercosis.

PMID- 19859891
TI  - [Fifteen years history of Parkinson's disease in Spain (1963-1977). A personal
      recollection].
AB  - Parkinson's disease (PD) and movement disorders, currently one of the leading
      subspecialties among Spanish neurologists, raised only modest interest during the
      seventies. This is well reflected in Revista de Neurologia, the first journal
      entirely devoted to Neurology in Spain. Along five years (1973-1977) only 3% out
      of papers published were devoted to this subject. The functions of the basal
      ganglia were poorly known. PD was regarded as a disorder of muscular tone,
      rigidity playing a pivotal role to explain most, if not all, parkinsonian signs.
      'Arteriosclerotic parkinsonism', whatever the symptoms might be, was applied to
      any form of parkinsonism occurring after the age of sixty. Such cases were
      usually treated by general practitioners, while younger patients were as a rule
      channeled for stereotactic surgery. Initial experience on levodopa therapy in
      Spain began around 1970, the drug being initially administered to severely
      disabled patients after long years of disease course. This, and probably because
      of the use of somewhat liberal doses of the new drug as well, severe choreiform
      dyskinesias were particularly common. Unexpectedly, neurologists were newly
      confronted to unusual, levodopa-related behavioral effects, such as manic
      behavior and overt hypersexuality, arising interest on non-motor aspects of PD,
      which had been mostly neglected at the time. Generalized awareness among
      physicians of PD as a common disorder in a wide age range in the general
      population, recognition of early signs and, most important, availability of an
      effective therapy, prompted widespread interest of Spanish neurologists on
      parkinsonism.

PMID- 19859890
TI  - [Cell and ex vivo gene therapy: advances in the treatment of central nervous
      system disorders].
AB  - INTRODUCTION: The direct application of different types of cells to the central
      nervous system (CNS) by means of transplants, so-called cell therapy, is an
      experimental approach that promotes the characterisation of the cell and
      molecular mechanisms involved in the development, plasticity and regeneration of
      damage to the CNS. Knowledge of the pathology and aetiology of neurodegenerative
      diseases, which are frequently related to the neurodegeneration of selected types
      of cells and/or deficiency of particular neurotransmitters, has led to research
      on means to obtain cell lines with specific characteristics. DEVELOPMENT: In some
      cases these cells become genetically transformed to produce large amounts of
      neurotransmitters or neurotrophic factors, the well-known ex vivo gene therapy,
      so that they can be used as therapeutic alternatives in pathologies affecting the
      CNS. For example, reports have been published of the beneficial effects of these
      therapies in studies with humans and in different models of neurodegenerative
      diseases, such as Huntington's disease and Parkinson's disease, and in epilepsy.
      The aim of this work is to review the different studies in which transplants of
      neuronal and non-neuronal cells have been used and which have served to further
      our knowledge of the CNS, of diseases that affect it and of possible therapeutic
      alternatives. CONCLUSIONS: Ex vivo cell therapy and gene therapy have helped to
      expand our knowledge about plasticity and the mechanisms and factors that promote
      cell integration within the central nervous system. Although behavioural
      improvements have been reported in animal and human models, further work is still
      required on these studies to clear up a number of dubious points. Ex vivo cell
      therapy and gene therapy in the nervous system constitute an important
      methodological tool with therapeutic possibilities that deserve further study.

PMID- 19859892
TI  - [Paralysis of upward gaze and eyelid retraction as isolated symptoms of posterior
      commissure infarction].

PMID- 19859894
TI  - [Effectiveness of levetiracetam in a patient with chronic motor tics, Rolandic
      epilepsy and attentional and behavioural disorder].

PMID- 19859895
TI  - [Science of survival].

PMID- 19859896
TI  - [Preserving and enhancing instruments of communication in the Ibero-American
      neurosciences].

PMID- 19859897
TI  - Giant placental chorioangioma: natural history and pregnancy outcome.
AB  - OBJECTIVES: Giant placental chorioangiomas are associated with a high prevalence
      of pregnancy complications and a poor perinatal outcome. The aim of the study was
      to evaluate the natural history, intrauterine treatment and outcome of
      pregnancies complicated by giant placental chorioangioma. METHODS: This was a
      retrospective study of 19 cases of giant placental chorioangioma, in which the
      natural history, intrauterine treatment and outcome of pregnancy were evaluated.
      RESULTS: Eighteen of the 19 cases were associated with a wide variety of fetal
      complications, including polyhydramnios, growth restriction, hyperdynamic
      circulation, cardiomegaly, anemia and non-immune hydrops. Two-thirds of the cases
      developed complications that required either elective delivery for fetal growth
      restriction (n = 6) or intervention for cardiovascular effects (n = 7). Fetal
      therapy, when required, was tailored to the particular complication and resulted
      in a successful pregnancy in all cases. CONCLUSIONS: The presence of large
      placental chorioangioma is associated with the development of fetal growth
      restriction and hyperdynamic state in a significant number of cases. This series
      elucidates some of the putative underlying mechanisms for these complications,
      and reports on a safe and effective treatment modality, percutaneous ultrasound
      guided interstitial laser therapy.

PMID- 19859899
TI  - Cochlear implantation in a profoundly deaf patient who also suffers from multiple
      sclerosis--a case study.
AB  - Outcomes of cochlear implantation in individuals with known central nervous
      system conditions are varied. Long-standing deafness is also thought to correlate
      negatively with auditory performance in post-linguistically deaf adult implant
      users. We present a case study of cochlear implantation in a post-lingual adult
      having bilateral profound hearing loss for over 30 years in addition to multiple
      sclerosis unrelated to his deafness. Assessment of benefit in terms of speech
      perception ability and quality of life reveal that long-term auditory deprivation
      and co-incidental multiple sclerosis are not a contraindication for cochlear
      implantation.

PMID- 19859898
TI  - A biodegradable scaffold for the treatment of a diaphyseal bone defect of the
      tibia.
AB  - The aim of this study was to compare angiogenesis and osteogenesis occurring
      within 8.0 mm diaphyseal defects created in canine tibiae treated using autograft
      or a biodegradable bone scaffold. All tibiae were reamed to 7.0 mm and fixed with
      a 6.5-mm statically locked intramedullary nail. Each of the 18 canines as
      allotted to one of three treatment groups: (1) left empty (N = 5), (2) treated
      with iliac crest autograft (N = 6), or (3) treated with a PLGA/calcium phosphate
      biodegradable scaffold (N = 7). Fluorescent markers were given at successive time
      periods: calcein green at 6 weeks, xylenol orange at 9 weeks, and tetracycline at
      11 and 14 weeks. Animals were sacrificed at 15 weeks and their legs were perfused
      with a radio opaque compound. Samples were analyzed using Micro CT, bright-field
      microscopy and fluorescent microscopy. Scaffold samples were found to have
      significantly greater bone formation (p = 0.015) and blood vessel formation (p <
      0.001) at their osteotomy sites than autograft samples. Bone formation rate in
      the periosteum was significantly greater in the autograft samples than the
      scaffold samples for all time periods. Bone formation at the osteotomy site was
      found to be significantly greater when associated with greater blood vessel
      formation (p = 0.026). The PLGA/calcium phosphate biodegradable scaffold we have
      employed supports angiogenesis within a segmental tibial defect that has adequate
      soft tissue coverage.

PMID- 19859900
TI  - Bevacizumab and ranibizumab on microvascular endothelial cells: A comparative
      study.
AB  - Given its broad effects in endothelium, vascular endothelial growth factor (VEGF)
      represents the primary rate-limiting step of angiogenesis. Therefore, VEGF
      targeting therapies were soon developed. Bevacizumab and ranibizumab are two of
      these therapeutic agents already in clinical use. Bevacizumab was first used for
      cancer treatment, whereas ranibizumab was designed to target choroidal
      neovascularization, the main cause of blindness in age-related macular
      degeneration. The present study aims to compare the multiple effects of
      bevacizumab and ranibizumab in human microvascular endothelial cells (HMECs).
      HMEC cultures were established and treated during 24 h with the anti-VEGF agents
      within the intravitreal-established concentration range or excipients. Analyses
      of VEGF content in cell media and VEGF receptor-2 (VEGFR-2) expression in cell
      lysates were performed. No cell cytotoxicity (MTS assay) was found in anti-VEGF
      treated cultures at any concentration. Apoptosis (TUNEL assay) was significantly
      increased and cell proliferation (BrdU assay), migration (transwell assay) and
      assembly into vascular structures were significantly reduced by incubation with
      both agents at the two doses used. These findings were accompanied by a strong
      decrease in VEGF release, and in phosphorylated VEGFR-2 and Akt expression for
      both agents at the clinical concentration. Interestingly, phosphorylated Erk was
      only significantly reduced upon bevacizumab treatment. In addition, proliferation
      was more affected by ranibizumab, whereas migration, capillary formation, and
      phosphorylated VEGFR2 expression were significantly reduced by bevacizumab as
      compared to ranibizumab. Therefore, although both agents presented anti
      angiogenic actions, distinct effects were exerted by the two molecules in HMEC.
      These findings suggest that a careful confirmation of these effects in clinical
      settings is mandatory.

PMID- 19859901
TI  - Quantitative analysis of alternative transcripts of human PCDH11X/Y genes.
AB  - The Protocadherin 11X/Y (PCDH11X/Y) gene pair has been proposed as a carrier of
      the variation relating to cerebral asymmetry and psychosis on the ground that the
      Y gene was generated by duplication at 6 million years (close to the chimpanzee
      human separation) and there is a case for an X/Y determinant of cerebral
      asymmetry. The present article investigated the patterns of alternative splicing
      and expression of the PCDH11X/Y genes. Twelve alternative transcripts of
      PCDH11X/Y genes were presently identified by in silico analysis. To investigate
      the biological roles of alternative transcripts of PCDH11X/Y genes, the
      transcripts were analyzed by real-time reverse transcription-polymerase chain
      reaction amplification. A total of 31 normal tissues including 11 different
      regions of human brain were used to investigate a wide spectrum of expression
      profiles. Dominant expression patterns were identified in several tissues (Tx1
      fetal liver; Tx3-adult brain; Tx4-adult brain and kidney; Tx5-bone marrow; Ty1
      fetal brain; Ty2-adrenal gland). Tx4 transcripts showed specific expression
      patterns in olfactory tissues. The findings can guide functional investigation of
      neuropsychiatric disorders.

PMID- 19859902
TI  - Racial differences in follow-up of abnormal mammography findings among
      economically disadvantaged women.
AB  - BACKGROUND: In the United States, and particularly in South Carolina, African
      American women suffer disproportionately higher mortality rates from breast
      cancer than European-American women. The timeliness of patient adherence to the
      follow-up of mammographic abnormalities may influence prognosis and survival. The
      objective of the current investigation was to examine racial differences in the
      completion and completion time of a diagnostic workup after the finding of a
      suspicious breast abnormality. METHODS: Study participants of the Best Chance
      Network, a statewide service program that provides free mammography screening to
      economically disadvantaged and medically underserved women, were included in the
      study. Racial differences in tumor characteristics and adherence to recommended
      workup were tested using chi-square tests and t tests. Logistic and Cox
      regression modeling was used to assess the relation between workup completion and
      other factors among African-American women and European-American women. RESULTS:
      Completion of the workup was associated with the number of previous procedures
      and income, and no significant differences were noted by race. The amount of time
      to completion of the workup was influenced by previous procedures, income, and
      race. After accounting for completion time, African-American women were 12% less
      likely than European-American women to complete the recommended workup (hazard
      ratio, 0.88; P=.01). CONCLUSIONS: The results from this study established a
      racial disparity in the time to completion of a diagnostic workup among Best
      Chance Network participants. These findings highlight the importance of
      understanding the factors associated with delays in and adherence to completing
      the recommended workup when breast abnormalities are detected in mammograms.

PMID- 19859903
TI  - Association between polymorphisms in the metallophosphoesterase (MPPE1) gene and
      bipolar disorder.
AB  - Genetic linkage studies in bipolar disorder (BPD) suggest that a susceptibility
      locus exists on chromosome 18p11. The metallophosphoesterase (MPPE1) gene maps to
      this region. Dysregulation of protein phosphorylation and subsequent abnormal
      cellular signaling has been postulated to be involved in neuropsychiatric
      disorders thus making MPPE1 a plausible biological candidate gene for BPD. In
      this study, we hypothesized that genetic variation in the MPPE1 gene contributes
      to BPD. We tested this hypothesis by genotyping four SNPs (rs871044; rs3974590;
      rs593713; rs602201) in BPD patients (n = 570) and healthy controls (n = 725).
      Genotypes and allele frequencies were compared between groups using Chi square
      contingency analysis. Linkage disequilibrium (LD) between markers was calculated
      and estimated haplotype frequencies were compared between groups. Single marker
      analysis revealed an association of rs3974590 with BPD (P = 0.009; permutation
      corrected P = 0.046). Haplotype analysis did not show any significant association
      with disease after permutation correction. Our results provide evidence of an
      association between a polymorphism in the MPPE1 gene and BPD. Additional studies
      are necessary to confirm and elucidate the role of MPPE1 as a susceptibility gene
      for BPD on chromosome 18p.

PMID- 19859905
TI  - Mutation screening of the DTNBP1 exonic sequence in 669 schizophrenics and 710
      controls using high-resolution melting analysis.
AB  - A large number of independent studies have reported evidence for association
      between the dysbindin gene (DTNBP1) and schizophrenia; however, specific risk
      alleles have been not been implicated as causal. In this study we set out to
      perform a comprehensive assessment of DNA variation within the exonic sequence of
      DTNBP1. To achieve this we optimized a high-resolution melting analysis (HRMA)
      protocol and applied it to screen all 11 DTNBP1 exons for DNA variants in a
      sample of 669 cases and 710 controls from the UK. Despite identifying seven
      exonic variants with a minor allele frequency (MAF) >0.01, none was significantly
      associated with schizophrenia (minimum P = 0.054), showing that the strong
      association we previously reported in this sample is not the result of
      association to a common functional variant located within the exonic sequence of
      any of the three major DTNBP1 transcripts. We also sought additional support for
      DTNBP1 as a susceptibility gene for schizophrenia by testing the hypothesis that
      rare exonic highly penetrant variants exist at the DTNBP1 locus. Our analysis
      failed to identify an enrichment of rare functional variants in the patients
      compared to the controls. Taken as a whole, this data demonstrate that if DTNBP1
      is a risk gene for schizophrenia then risk is not conferred by mutations that
      affect the structure of the dysbindin protein.

PMID- 19859906
TI  - Antibiotic prophylaxis before amniocentesis: a proven and effective method to
      preserve fetal life.

PMID- 19859907
TI  - Antibiotic prophylaxis for amniocentesis.

PMID- 19859904
TI  - Association and interaction analysis of variants in CHRNA5/CHRNA3/CHRNB4 gene
      cluster with nicotine dependence in African and European Americans.
AB  - Several previous genome-wide and targeted association studies revealed that
      variants in the CHRNA5-CHRNA3-CHRNB4 (CHRNA5/A3/B4) gene cluster on chromosome 15
      that encode the alpha5, alpha3, and beta4 subunits of the nicotinic acetylcholine
      receptors (nAChRs) are associated with nicotine dependence (ND) in European
      Americans (EAs) or others of European origin. Considering the distinct linkage
      disequilibrium patterns in European and other ethnic populations such as African
      Americans (AAs), it would be interesting to determine whether such associations
      exist in other ethnic populations. We performed a comprehensive association and
      interaction analysis of the CHRNA5/A3/B4 cluster in two ethnic samples to
      investigate the role of variants in the risk for ND, which was assessed by
      Smoking Quantity, Heaviness Smoking Index, and Fagerstrom test for ND. Using a
      family-based association test, we found a nominal association of single
      nucleotide polymorphisms (SNPs) rs1317286 and rs8040868 in CHRNA3 with ND in the
      AA and combined AA and EA samples. Furthermore, we found that several haplotypes
      in CHRNA5 and CHRNA3 are nominally associated with ND in AA, EA, and pooled
      samples. However, none of these associations remained significant after
      correction for multiple testing. In addition, we performed interaction analysis
      of SNPs within the CHRNA5/A3/B4 cluster using the pedigree-based generalized
      multifactor dimensionality reduction method and found significant interactions
      within CHRNA3 and among the three subunit genes in the AA and pooled samples.
      Together, these results indicate that variants within CHRNA3 and among CHRNA5,
      CHRNA3, and CHRNB4 contribute significantly to the etiology of ND through gene
      gene interactions, although the association of each subunit gene with ND is weak
      in both the AA and EA samples.

PMID- 19859908
TI  - Non-invasive fetal lung assessment using diffusion-weighted imaging.
AB  - OBJECTIVES: The main goal was to develop a reproducible method for estimating the
      diffusion of water in human fetal lung tissue using diffusion-weighted imaging
      (DWI). A secondary objective was to determine the relationship of the apparent
      diffusion coefficients (ADCs) in the fetal lung to menstrual age and total lung
      volume. METHODS: Normal pregnant volunteers were scanned on a 1.5-Tesla (T)
      magnetic resonance imaging (MRI) system. The MRI system was equipped with 40-mT/m
      gradients (slew rate 200 T/m/s, rise time 0.2 ms). A six-channel body array coil
      was used for signal reception. Single-shot DWI utilized TE/TR 125/3400 ms, slice
      thickness 4 mm, field of view 280 mm x 280 mm, interslice gap 0.8 mm and a matrix
      of 128 x 128. The voxel size was 2.5 mm x 2.5 mm x 4.0 mm. Two b-values (0 and
      1000) were chosen along three orthogonal directions. ADC maps were created using
      assigned b-values. Simple linear regression was performed with Pearson
      correlation coefficient. Interexaminer and intraexaminer bias, and 95% limits of
      agreement (LOA) were determined using Bland-Altman plots. RESULTS: Forty-seven
      scans were performed at a mean +/- SD of 29.2 +/- 4.5 weeks. The median
      coefficient of variation for ADC was 5.6% (interquartile range, 4.0-8.1%). No
      differences in ADC values were found between right and left lungs. Normally
      distributed ADC measurements were not significantly correlated with either total
      lung volume (r(2) = 0.0001, P = 0.94) or menstrual age (r(2) = 0.003, P = 0.70).
      The mean ADC value was 1.75 (95% CI, 1.63-1.86). Mean +/- SD intraexaminer bias
      was -0.15 +/- 2.3 (95% LOA, -4.7 to + 4.4) and interexaminer bias was 2.2 +/- 3.5
      (95% LOA, -4.7 to + 9.1). CONCLUSIONS: Our findings suggest that ADC measurements
      of the fetal lung are reproducible between blinded examiners and are independent
      of menstrual age, as well as lung volume.

PMID- 19859909
TI  - Cholera toxin-sensitive GTP-binding protein-coupled activation of augmenter of
      liver regeneration (ALR) receptor and its function in rat kupffer cells.
AB  - Mitogenic effect of augmenter of liver regeneration (ALR), a protein produced and
      released by hepatocytes, on hepatocytes in vivo but not in vitro suggests that
      the effect is mediated by nonparenchymal cells. Since mediators produced by
      Kupffer cells are implicated in hepatic regeneration, we investigated receptor
      for ALR and its functions in rat Kupffer cells. Kupffer cells were isolated from
      rat liver by enzymatic digestion and centrifugal elutriation. Radioligand
      ([(125)I] ALR) receptor binding, ALR-induced GTP/G-protein association, and
      nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and interleukin-6 (IL-6)
      synthesis were determined. High-affinity receptor for ALR, belonging to the G
      protein family, with K(d) of 1.25 +/- 0.18 nM and B(max) of 0.26 +/- 0.02
      fmol/microg DNA was identified. ALR stimulated NO, TNF-alpha, and IL-6 synthesis
      via cholera toxin-sensitive G-protein, as well as p38-MAPK activity and nuclear
      translocation of NFkappaB. While inhibitor of NFkappaB (MG132) inhibited ALR
      induced NO synthesis, MG132 and p38-MAPK inhibitor (SB203580) abrogated ALR
      induced TNF-alpha and IL-6 synthesis. ALR also prevented the release of
      mediator(s) from Kupffer cells that cause inhibition of DNA synthesis in
      hepatocytes. Administration of ALR to 40% partially hepatectomized rats increased
      expression of TNF-alpha, IL-6, and inducible nitric oxide synthase (iNOS) and
      caused augmentation of hepatic regeneration. These results demonstrate specific G
      protein coupled binding of ALR and its function in Kupffer cells and suggest that
      mediators produced by ALR-stimulated Kupffer cells may elicit physiologically
      important effects on hepatocytes.

PMID- 19859911
TI  - Human testicular orphan receptor 4 enhances thyroid hormone receptor signaling.
AB  - The thyroid hormone receptor (TR) and human testicular orphan receptor 4 (TR4)
      belong to the nuclear hormone receptor superfamily. They are ligand-dependent
      transcription factors. TR and TR4 bind to a similar thyroid response element
      (TRE), known as a direct repeat with four nucleotide spacing (DR4). This study
      examined the possible interaction or cross-talking between those two receptors.
      We hypothesized that protein-protein interaction between TR4 and TR may promote
      TR-mediated transcriptional activity. Glutathione S-transferase pull-down and
      immunoprecipitation assays showed direct interaction between TR and TR4.
      Electrophoretic mobility-shift assay demonstrated that TR and TR4 could co-occupy
      the same TRE. The interaction between TR4 and TR may enhance regulation of genes
      targeted by TR, such as furin, fibrinogen, cdk2 and p21 expression. We found that
      TR4 function is similar with TR as TR4 alone could regulate expression of some TR
      target genes, and could increase cell migration or inhibit cell proliferation.
      Importantly, the TR-dependent inhibition of cell proliferation and stimulation of
      cell migration are more enhanced in the HepG2-TR cells stably over-expressing
      TR4. Overall, TR4 not only has modulation abilities similar to TR but also can
      cross-talk with TR and promote the TR signaling pathway.

PMID- 19859912
TI  - The influence of violent and nonviolent computer games on implicit measures of
      aggressiveness.
AB  - We examined the causal relationship between playing violent video games and
      increases in aggressiveness by using implicit measures of aggressiveness, which
      have become important for accurately predicting impulsive behavioral tendencies.
      Ninety-six adults were randomly assigned to play one of three versions of a
      computer game that differed only with regard to game content (violent, peaceful,
      or abstract game), or to work on a reading task. In the games the environmental
      context, mouse gestures, and physiological arousal-as indicated by heart rate and
      skin conductance-were kept constant. In the violent game soldiers had to be shot,
      in the peaceful game sunflowers had to be watered, and the abstract game simply
      required clicking colored triangles. Five minutes of play did not alter trait
      aggressiveness, yet an Implicit Association Test detected a change in implicit
      aggressive self-concept. Playing a violent game produced a significant increase
      in implicit aggressive self-concept relative to playing a peaceful game. The well
      controlled study closes a gap in the research on the causality of the link
      between violence exposure in computer games and aggressiveness with specific
      regard to implicit measures. We discuss the significance of importing recent
      social-cognitive theory into aggression research and stress the need for further
      development of aggression-related implicit measures.

PMID- 19859910
TI  - TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function
      after cigarette smoke exposure.
AB  - Skeletal muscle dysfunction contributes to exercise limitation in COPD. In this
      study cigarette smoke exposure was hypothesized to increase expression of the
      inflammatory cytokine, TNF-alpha, thereby suppressing PGC-1alpha, and hence
      affecting down stream molecules that regulate oxygen transport and muscle
      function. Furthermore, we hypothesized that highly vascularized oxidative
      skeletal muscle would be more susceptible to cigarette smoke than less well
      vascularized glycolytic muscle. To test these hypotheses, mice were exposed to
      cigarette smoke daily for 8 or 16 weeks, resulting in 157% (8 weeks) and 174% (16
      weeks) increases in serum TNF-alpha. Separately, TNF-alpha administered to C2C12
      myoblasts was found to dose-dependently reduce PGC-1alpha mRNA. In the smoke
      exposed mice, PGC-1alpha mRNA was decreased, by 48% in soleus and 23% in EDL. The
      vascular PGC-1alpha target molecule, VEGF, was also down-regulated, but only in
      the soleus, which exhibited capillary regression and an oxidative to glycolytic
      fiber type transition. The apoptosis PGC-1alpha target genes, atrogin-1 and
      MuRF1, were up-regulated, and to a greater extent in the soleus than EDL. Citrate
      synthase (soleus-19%, EDL-17%) and beta-hydroxyacyl CoA dehydrogenase (beta-HAD)
      (soleus-22%, EDL-19%) decreased similarly in both muscle types. There was loss of
      body and gastrocnemius complex mass, with rapid soleus but not EDL fatigue and
      diminished exercise endurance. These data suggest that in response to smoke
      exposure, TNF-alpha-mediated down-regulation of PGC-1alpha may be a key step
      leading to vascular and myocyte dysfunction, effects that are more evident in
      oxidative than glycolytic skeletal muscles.

PMID- 19859913
TI  - Cell line cross-contamination initiative: an interactive reference database of
      STR profiles covering common cancer cell lines.

PMID- 19859914
TI  - Do the dose or route of administration of norethisterone acetate as a part of
      hormone therapy play a role in risk of breast cancer: national-wide case-control
      study from Finland.
AB  - We examined the associations between various doses and routes of administration
      of norethisterone acetate (NETA) in estrogen-progestagen therapy (EPT) and the
      risk of breast cancer in Finland. All Finnish women with first invasive breast
      cancer diagnosed between the ages of 50-62 during 1995-2007 (n = 9,956) were
      identified from the Finnish Cancer Registry. For each case, 3 controls of the
      same age were retrieved from the Finnish Population Register. The use of
      estradiol+NETA-therapy by the cases and controls was traced from the national
      Medical Reimbursement Registry. The data were analyzed with multivariate
      conditional logistic regression, adjusting for parity, age at the first birth,
      and health care district. The continuous mode of NETA use tended to be associated
      with a higher rate ratio for breast cancer than the sequential use. The use of
      continuous "low" dose (NETA 0.5 mg + estradiol 1.0 mg) was associated with an
      increased rate ratio of breast cancer already in less than 3 years of use (odds
      ratio 1.94; 95% confidence interval 1.39-2.70) while a risk elevation for "high"
      dose (NETA 1.0 mg + estradiol 2.0 mg) was seen after 3 years use (1.71; 1.51
      2.54). Oral and transdermal use of NETA were accompanied with comparable risks
      for breast cancer. In conclusion, the dose or route of administration of NETA in
      EPT do not modify the risks for breast cancer.

PMID- 19859915
TI  - Sodium MRI using a density-adapted 3D radial acquisition technique.
AB  - A density-adapted three-dimensional radial projection reconstruction pulse
      sequence is presented which provides a more efficient k-space sampling than
      conventional three-dimensional projection reconstruction sequences. The gradients
      of the density-adapted three-dimensional radial projection reconstruction pulse
      sequence are designed such that the averaged sampling density in each spherical
      shell of k-space is constant. Due to hardware restrictions, an inner sphere of k
      space is sampled without density adaption. This approach benefits from both the
      straightforward handling of conventional three-dimensional projection
      reconstruction sequence trajectories and an enhanced signal-to-noise ratio (SNR)
      efficiency akin to the commonly used three-dimensional twisted projection imaging
      trajectories. Benefits for low SNR applications, when compared to conventional
      three-dimensional projection reconstruction sequences, are demonstrated with the
      example of sodium imaging. In simulations of the point-spread function, the SNR
      of small objects is increased by a factor 1.66 for the density-adapted three
      dimensional radial projection reconstruction pulse sequence sequence. Using
      analytical and experimental phantoms, it is shown that the density-adapted three
      dimensional radial projection reconstruction pulse sequence allows higher
      resolutions and is more robust in the presence of field inhomogeneities. High
      quality in vivo images of the healthy human leg muscle and the healthy human
      brain are acquired. For equivalent scan times, the SNR is up to a factor of 1.8
      higher and anatomic details are better resolved using density-adapted three
      dimensional radial projection reconstruction pulse sequence.

PMID- 19859916
TI  - Accurate free energy calculation along optimized paths.
AB  - The path-based methods of free energy calculation, such as thermodynamic
      integration and free energy perturbation, are simple in theory, but difficult in
      practice because in most cases smooth paths do not exist, especially for large
      molecules. In this article, we present a novel method to build the transition
      path of a peptide. We use harmonic potentials to restrain its nonhydrogen atom
      dihedrals in the initial state and set the equilibrium angles of the potentials
      as those in the final state. Through a series of steps of geometrical
      optimization, we can construct a smooth and short path from the initial state to
      the final state. This path can be used to calculate free energy difference. To
      validate this method, we apply it to a small 10-ALA peptide and find that the
      calculated free energy changes in helix-helix and helix-hairpin transitions are
      both self-convergent and cross-convergent. We also calculate the free energy
      differences between different stable states of beta-hairpin trpzip2, and the
      results show that this method is more efficient than the conventional molecular
      dynamics method in accurate free energy calculation.

PMID- 19859917
TI  - Quantum mechanics and quasiclassical study of the H/D+FO --> OH/OD+F, HF/DF+O
      reactions: chemical stereodynamics.
AB  - The time-dependent quantum wave packet and the quasi-classical trajectory (QCT)
      calculations for the title reactions are carried out using three recent-developed
      accurate potential energy surfaces of the 1(1)A', 1(3)A', and 1(3)A'' states. The
      two commonly used polarization-dependent differential cross sections,
      dsigma(00)/domega(t), dsigma(20)/domega(t), with omega(t) being the polar
      coordinates of the product velocity omega', and the three angular distributions,
      P(theta(r)), P(Phi(r)), and P(theta(r),Phi(r)), with theta(r), Phi(r) being the
      polar angles of the product angular momentum, are generated in the center-of-mass
      frame using the QCT method to gain insight into the alignment and the orientation
      of the product molecules. Influences of the potential energy surface, the
      collision energy, and the isotope mass on the stereodynamics are shown and
      discussed. Validity of the QCT calculation has been examined and proved in the
      comparison with the quantum wave packet calculation.

PMID- 19859918
TI  - Initial results on in vivo human coronary MR angiography at 7 T.
AB  - Seven tesla (T) MR imaging is potentially promising for the morphologic
      evaluation of coronary arteries because of the increased signal-to-noise ratio
      compared to lower field strengths, in turn allowing improved spatial resolution,
      improved temporal resolution, or reduced scanning times. However, there are a
      large number of technical challenges, including the commercial 7 T systems not
      being equipped with homogeneous body radiofrequency coils, conservative specific
      absorption rate constraints, and magnified sample-induced amplitude of
      radiofrequency field inhomogeneity. In the present study, an initial attempt was
      made to address these challenges and to implement coronary MR angiography at 7 T.
      A single-element radiofrequency transmit and receive coil was designed and a 7 T
      specific imaging protocol was implemented, including significant changes in scout
      scanning, contrast generation, and navigator geometry compared to current
      protocols at 3 T. With this methodology, the first human coronary MR images were
      successfully obtained at 7 T, with both qualitative and quantitative findings
      being presented.

PMID- 19859919
TI  - Bis(4'-dibutylaminostyryl)benzene: spectroscopic behavior upon protonation or
      methylation.
AB  - We have investigated the UV/Vis absorption and emission of 1,4-bis(4'
      dibutylaminostyryl)benzene (1) upon protonation with trifluoroacetic acid in
      dichloromethane and in acetonitrile. We find that 1 does not display
      significantly dynamic acidity in the excited state, that is, it is not a
      photoacid. Three protonation states of 1 were investigated, all of which,
      neutral, singly protonated, and bis-protonated, are fluorescent. As an isolable
      model for the mono-protonated species, a methylated derivative of 1 was prepared
      by reaction with methyl triflate. This species displays redshifted emission but
      similar absorption as the non-quaternized parent, 1. The strong observed emission
      of all three protonated states of 1 suggests that the kinetic photoacidity of 1*
      is low or absent. We assume that the lifetime of the excited state is too short
      to allow solvent reorganization and therefore we cannot make a statement on the
      thermodynamic photoacidity of the protonated forms of 1.

PMID- 19859920
TI  - Synthesis of iron oxide nanoparticles in Listeria innocua Dps (DNA-binding
      protein from starved cells): a study with the wild-type protein and a catalytic
      centre mutant.
AB  - A comparative analysis of the magnetic properties of iron oxide nanoparticles
      grown in the cavity of the DNA-binding protein from starved cells of the
      bacterium Listeria innocua, LiDps, and of its triple-mutant lacking the catalytic
      ferroxidase centre, LiDps-tm, is presented. TEM images and static and dynamic
      magnetic and electron magnetic resonance (EMR) measurements reveal that, under
      the applied preparation conditions, namely alkaline pH, high temperature (65
      degrees C), exclusion of oxygen, and the presence of hydrogen peroxide, maghemite
      and/or magnetite nanoparticles with an average diameter of about 3 nm are
      mineralised inside the cavities of both LiDps and LiDps-tm. The magnetic
      nanoparticles (MNPs) thus formed show similar magnetic properties, with
      superparamagnetic behaviour above 4.5 K and a large magnetic anisotropy.
      Interestingly, in the EMR spectra an absorption at half-field is observed, which
      can be considered as a manifestation of the quantum behaviour of the MNPs. These
      results indicate that Dps proteins can be advantageously used for the production
      of nanomagnets at the interface between molecular clusters and traditional MNPs
      and that the presence of the ferroxidase centre, though increasing the efficiency
      of nanoparticle formation, does not affect the nature and fine structure of the
      MNPs. Importantly, the self-organisation of MNP-containing Dps on HRTEM grids
      suggests that Dps-enclosed MNPs can be deposited on surfaces in an ordered
      fashion.

PMID- 19859921
TI  - Achieving high affinity towards a bacterial lectin through multivalent
      topological isomers of calix[4]arene glycoconjugates.
AB  - A family of seven topologically isomeric calix[4]arene glycoconjugates was
      prepared through the synthesis of a series of alkyne-derivatised calix[4]arene
      precursors that are suitable for the attachment of sugar moieties by microwave
      assisted copper(I)-catalysed azide-alkyne cycloaddition (CuAAC). The
      glycoconjugates thus synthesised comprised one mono-functionalised derivative,
      two 1,2- or 1,3-divalent regioisomers, one trivalent and three tetravalent
      topoisomers in the cone, partial cone or 1,3-alternate conformations. The
      designed glycoconjugates were evaluated as ligands for the galactose-binding
      lectin PA-IL from the opportunistic bacterium Pseudomonas aeruginosa, a major
      causative agent of lung infections in cystic fibrosis patients. Binding
      affinities were determined by isothermal titration calorimetry (ITC), and the
      interaction with the lectin was shown to be strongly dependant on both the
      valence and the topology. Whereas the trivalent conjugate displayed enhanced
      affinity when compared to a monosaccharide model, the tetravalent conjugates are
      to-date the highest-affinity ligands measured by ITC. The topologies presenting
      carbohydrates on both faces of calixarene are the most potent ones with
      dissociation constants of approximately 200 nM. Molecular modelling suggests that
      such a multivalent molecule can efficiently chelate two of the binding sites of
      the tetrameric lectin; this explains the 800-fold increase of affinity achieved
      by the tetravalent molecule. Surface plasmon resonance (SPR) experiments
      confirmed that this glycoconjugate is the strongest inhibitor for binding of PA
      IL to galactosylated surfaces for potential applications as an anti-adhesive
      agent.

PMID- 19859922
TI  - Linkage isomerism and spin frustration in heterometallic rings: synthesis,
      structural characterization, and magnetic and EPR spectroscopic studies of
      Cr(7)Ni, Cr(6)Ni(2), and Cr(7)Ni(2) rings templated about imidazolium cations.
AB  - The synthesis and structural characterization of three heterometallic rings
      templated about imidazolium cations is reported. The compounds are [2,4-DiMe
      ImidH][Cr(7)Ni(II)F(8)(O(2)CtBu)(16)] 1 (2,4-DiMe-ImidH=the cation of 2,4
      dimethylimidazole), [ImidH](2)[Cr(6)Ni(II) (2)F(8)(O(2)CCtBu)(16)] 2 (ImidH=the
      cation of imidazole), and [1-Bz-ImidH](2) [Cr(7)Ni(II) (2)F(9)(O(2)CtBu)(18)] 3
      (1-Bz-ImidH=the cation of 1-benzylimidazole). The structures show the formation
      of octagonal arrays of metals for 1 and 2 and a nonagon of metal centers for 3.
      In all cases the edges of the polygon are bridged by a single fluoride and two
      pivalate ligands, and the position of the divalent metal centers cannot be
      distinguished by X-ray diffraction. Magnetic studies combined with EPR
      spectroscopy allow the characterization of the magnetic states of the compounds.
      In each case the exchange is antiferromagnetic with a magnetic exchange parameter
      J approximately -5.8 cm(-1), and it is not possible to differentiate the exchange
      between two Cr(III) centers (J(CrCr)) from the exchange between a Cr(III) and a
      Ni(II) center (J(CrNi)). For 2 there is evidence for the presence of at least
      two, possibly four, linkage isomers of the heterometallic ring, caused by the
      presence of two divalent metal centers in the ring. The EPR spectroscopy of 3
      suggests an S=1/2 ground state of the ring and that it is likely that only one
      linkage isomer is present.

PMID- 19859923
TI  - Reactivity and regioselectivity of noble gas endohedral fullerenes Ng@C(60) and
      Ng(2)@C(60) (Ng=He-Xe).
AB  - Recently, it was shown that genuine Ng-Ng chemical bonds are present in the
      endohedral fullerenes Ng(2)@C(60) in the case of Ng=Xe, while it is more
      debatable whether a chemical bond exist for Ng=Ar and Kr. The lighter homologues
      with helium and neon are weakly bonded van der Waals complexes. The presence of a
      noble gas dimer inside the cage is expected to modify the exohedral reactivity of
      the C(60) cage with respect to that of free C(60). To investigate the impact of
      encapsulated diatomic noble gas molecules on the chemical reactivity of C(60), we
      analyzed the thermodynamics and the kinetics of [4+2] Diels-Alder cycloaddition
      of 1,3-cis-butadiene at all nonequivalent bonds in free C(60), Ng@C(60), and
      Ng(2)@C(60) (Ng=He, Ne, Ar, Kr, and Xe). Our BP86/TZP calculations reveal that
      introduction of single noble gas atoms in Ng@C(60) and noble gas dimers He(2) and
      Ne(2) in Ng(2)@C(60) has almost no effect on the exohedral reactivity compared to
      free C(60), in agreement with experimental results. In all these cases
      cycloaddition is clearly favored at the [6,6] bonds in the fullerene cage. For
      the endohedral compounds He(2)@C(60) and Ne(2)@C(60) a slight preference (by less
      than 2 kcal mol(-1)) for bonds closer to the C(5) symmetry axis is found. This
      picture changes dramatically for the endohedral compounds with heavier noble gas
      dimers. Encapsulation of these noble gas dimers clearly enhances the reaction,
      both under thermodynamic and kinetic control. Moreover, in the case of
      Xe(2)@C(60), addition to [6,6] and [5,6] bonds becomes equally viable. These
      reactivity changes in endohedral fullerenes are attributed to stabilization of
      the LUMO, increased fullerene strain energy, and greater compression of the
      encapsulated Ng(2) unit along the He to Xe series.

PMID- 19859925
TI  - Polymerisation of the dysprosium acetate dimer switches on single-chain
      magnetism.

PMID- 19859924
TI  - Cascade reactions in an all-enzyme nanoreactor.

PMID- 19859926
TI  - A highly enantioselective access to tetrahydroisoquinoline and beta-carboline
      alkaloids with simple noyori-type catalysts in aqueous media.

PMID- 19859927
TI  - Enantioselective palladium-catalyzed direct arylations at ambient temperature:
      access to indanes with quaternary stereocenters.

PMID- 19859928
TI  - Radical polymerization: reversing the irreversible?

PMID- 19859930
TI  - Electronic control of spin coupling in keplerate-type polyoxomolybdates.

PMID- 19859929
TI  - Specificity and mechanism of Acinetobacter baumanii nicotinamidase: implications
      for activation of the front-line tuberculosis drug pyrazinamide.

PMID- 19859931
TI  - Effects of fluorination on the folding kinetics of a heterodimeric coiled coil.

PMID- 19859932
TI  - Analysis of the self-assembly of 4x4 DNA tiles by temperature-dependent FRET
      spectroscopy.
AB  - Correct and efficient self-assembly of oligonucleotides into highly ordered
      superstructures essentially depends on the structural integrity and thermal
      stability of DNA motifs such as junctions or tiles that build up the
      superstructure. To investigate the assembly/disassembly process of DNA tiles, we
      recently described a microplate-based method employing Forster resonance energy
      transfer (FRET) spectroscopy, which enables the analysis of DNA superstructure
      formation in real time and with high throughput. This method allows thermodynamic
      parameters of the self-assembly process to be extracted, and we here apply it for
      detailed analysis of the self-assembly of five different 4x4 DNA tile motifs. To
      specifically investigate whether the FRET probes tethered to the DNA motifs
      report local thermodynamic stabilities in the immediate proximity of the
      chromophores, or whether the global stability of the entire motif is monitored,
      systematic variations of the labeling position within one tile are carried out.
      Combined with gel electrophoretic, UV spectroscopic, and microcalorimetric
      analysis, this study reveals that the FRET method mainly reports the
      thermodynamics of local microenvironment assembly, rather than that of the entire
      motif. Nonetheless, the thermodynamic data derived from FRET analysis are also
      influenced by the structural surroundings of the motif, and thus rapid and
      detailed analysis and identification of potential "weak points" within a
      superstructure which influence the structural integrity of a given tile design
      are enabled. Therefore, the microplate FRET method readily provides insights into
      the assembly process of complex DNA superstructures to verify and complement
      theoretical design approaches.

PMID- 19859933
TI  - Disease state prediction from resting state functional connectivity.
AB  - The application of multivoxel pattern analysis methods has attracted increasing
      attention, particularly for brain state prediction and real-time functional MRI
      applications. Support vector classification is the most popular of these
      techniques, owing to reports that it has better prediction accuracy and is less
      sensitive to noise. Support vector classification was applied to learn functional
      connectivity patterns that distinguish patients with depression from healthy
      volunteers. In addition, two feature selection algorithms were implemented (one
      filter method, one wrapper method) that incorporate reliability information into
      the feature selection process. These reliability feature selections methods were
      compared to two previously proposed feature selection methods. A support vector
      classifier was trained that reliably distinguishes healthy volunteers from
      clinically depressed patients. The reliability feature selection methods
      outperformed previously utilized methods. The proposed framework for applying
      support vector classification to functional connectivity data is applicable to
      other disease states beyond major depression.

PMID- 19859934
TI  - Complex-valued analysis of arterial spin labeling-based functional magnetic
      resonance imaging signals.
AB  - Cerebral blood flow-dependent phase differences between tagged and control
      arterial spin labeling images are reported. A biophysical model is presented to
      explain the vascular origin of this difference. Arterial spin labeling data
      indicated that the phase difference is largest when the arterial component of the
      signals is preserved but is greatly reduced as the arterial contribution is
      suppressed by postinversion delays or flow-crushing gradients. Arterial
      vasculature imaging by saturation data of activation and hypercapnia conditions
      showed increases in phase accompanying blood flow increases.An arterial spin
      labeling functional magnetic resonance imaging study yielded significant
      activation by magnitude-only, phase-only, and complex analyses when preserving
      the whole arterial spin labeling signal. After suppression of the arterial signal
      by postinversion delays, magnitude-only and complex models yielded similar
      activation levels, but the phase-only model detected nearly no activation. When
      flow crushers were used for arterial suppression, magnitude-only activation was
      slightly lower and fluctuations in phase were dramatically higher than when
      postinversion delays were used.Although the complex analysis performed did not
      improve detection, a simulation study indicated that the complex-valued
      activation model exhibits combined magnitude and phase detection power and thus
      maximizes sensitivity under ideal conditions. This suggests that, as arterial
      spin labeling imaging and image correction methods develop, the complex-valued
      detection model may become helpful in signal detection.

PMID- 19859935
TI  - Delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) of hip joint
      cartilage in femoroacetabular impingement (FAI): Are pre- and postcontrast
      imaging both necessary?
AB  - The purpose of this study was to assess if delayed gadolinium MRI of cartilage
      using postcontrast T(1) (T(1Gd)) is sufficient for evaluating cartilage damage in
      femoroacetabular impingement without using noncontrast values (T(10)). T(1Gd) and
      DeltaR(1) (1/T(1Gd) - 1/T(10)) that include noncontrast T(1) measurements were
      studied in two grades of osteoarthritis and in a control group of asymptomatic
      young-adult volunteers. Differences between T(1Gd) and DeltaR(1) values for
      femoroacetabular impingement patients and volunteers were compared. There was a
      very high correlation between T(1Gd) and DeltaR(1) in all study groups. In the
      study cohort with Tonnis grade 0, correlation (r) was -0.95 and -0.89 with Tonnis
      grade 1 and -0.88 in asymptomatic volunteers, being statistically significant (P
      < 0.001) for all groups. For both T(1Gd) and DeltaR(1), a statistically
      significant difference was noted between patients and control group. Significant
      difference was also noted for both T(1Gd) and DeltaR(1) between the patients with
      Tonnis grade 0 osteoarthritis and those with grade 1 changes. Our results prove a
      linear correlation between T(1Gd) and DeltaR(1), suggesting that T(1Gd)
      assessment is sufficient for the clinical utility of delayed gadolinium MRI of
      cartilage in this setting and additional time-consuming T(10) evaluation may not
      be needed.

PMID- 19859936
TI  - High-frequency mode conversion technique for stiff lesion detection with magnetic
      resonance elastography (MRE).
AB  - A novel imaging technique is described in which the mode conversion of
      longitudinal waves is used for the qualitative detection of stiff lesions within
      soft tissue using magnetic resonance elastography (MRE) methods. Due to the
      viscoelastic nature of tissue, high-frequency shear waves attenuate rapidly in
      soft tissues but much less in stiff tissues. By introducing minimally-attenuating
      longitudinal waves at a significantly high frequency into tissue, shear waves
      produced at interfaces by mode conversion will be detectable in stiff regions,
      but will be significantly attenuated and thus not detectable in the surrounding
      soft tissue. This contrast can be used to detect the presence of stiff tissue.
      The proposed technique is shown to readily depict hard regions (mimicking tumors)
      present in tissue-simulating phantoms and ex vivo breast tissue. In vivo
      feasibility is demonstrated on a patient with liver metastases in whom the tumors
      are readily distinguished. Preliminary evidence also suggests that quantitative
      stiffness measurements of stiff regions obtained with this technique are more
      accurate than those from conventional MRE because of the short shear wavelengths.
      This rapid, qualitative technique may lend itself to applications in which the
      localization of stiff, suspicious neoplasms is coupled with more sensitive
      techniques for thorough characterization.

PMID- 19859937
TI  - Magnetic susceptibility mapping of brain tissue in vivo using MRI phase data.
AB  - Phase images in susceptibility-weighted MRI of brain provide excellent contrast.
      However, the phase is affected by tissue geometry and orientation relative to the
      main magnetic field (B(0)), and phase changes extend beyond areas of altered
      susceptibility. Magnetic susceptibility, on the other hand, is an intrinsic
      tissue property, closely reflecting tissue composition. Therefore, recently
      developed inverse Fourier-based methods were applied to calculate susceptibility
      maps from high-resolution phase images acquired at a single orientation at 7 T in
      the human brain (in vivo and fixed) and at 11.7 T in fixed marmoset brain. In
      susceptibility images, the contrast of cortical layers was more consistent than
      in phase images and was independent of the structures' orientation relative to
      B(0). The contrast of iron-rich deep-brain structures (red nucleus and substantia
      nigra) in susceptibility images agreed more closely with iron-dominated R(2) (*)
      images than the phase image contrast, which extended outside the structures. The
      mean susceptibility in these regions was significantly correlated with their
      estimated iron content. Susceptibility maps calculated using this method overcome
      the orientation-dependence and non-locality of phase image contrast and seem to
      reflect underlying tissue composition. Susceptibility images should be easier to
      interpret than phase images and could improve our understanding of the sources of
      susceptibility contrast.

PMID- 19859938
TI  - High-contrast in vivo visualization of microvessels using novel FeCo/GC magnetic
      nanocrystals.
AB  - FeCo-graphitic carbon shell nanocrystals are a novel MRI contrast agent with
      unprecedented high per-metal-atom-basis relaxivity (r(1) = 97 mM(-1) sec(-1),
      r(2) = 400 mM(-1) sec(-1)) and multifunctional capabilities. While the
      conventional gadolinium-based contrast-enhanced angiographic magnetic MRI has
      proven useful for diagnosis of vascular diseases, its short circulation time and
      relatively low sensitivity render high-resolution MRI of morphologically small
      vascular structures such as those involved in collateral, arteriogenic, and
      angiogenic vessel formation challenging. Here, by combining FeCo-graphitic carbon
      shell nanocrystals with high-resolution MRI technique, we demonstrate that such
      microvessels down to approximately 100 mum can be monitored in high contrast and
      noninvasively using a conventional 1.5-T clinical MRI system, achieving a
      diagnostic imaging standard approximating that of the more invasive X-ray
      angiography. Preliminary in vitro and in vivo toxicity study results also show no
      sign of toxicity.

PMID- 19859939
TI  - Characterization of T(2)* heterogeneity in human brain white matter.
AB  - Recent in vivo MRI studies at 7.0 T have demonstrated extensive heterogeneity of
      T(2)* relaxation in white matter of the human brain. In order to study the origin
      of this heterogeneity, we performed T(2)* measurements at 1.5, 3.0, and 7.0 T in
      normal volunteers. Formalin-fixed brain tissue specimens were also studied using
      T(2)*-weighted MRI, histologic staining, chemical analysis, and electron
      microscopy. We found that T(2)* relaxation rate (R(2)* = 1/T(2)*) in white matter
      in living human brain is linearly dependent on the main magnetic field strength,
      and the T(2)* heterogeneity in white matter observed at 7.0 T can also be
      detected, albeit more weakly, at 1.5 and 3.0 T. The T(2)* heterogeneity exists
      also in white matter of the formalin-fixed brain tissue specimens, with prominent
      differences between the major fiber bundles such as the cingulum (CG) and the
      superior corona radiata. The white matter specimen with substantial difference in
      T(2)* has no significant difference in the total iron content, as determined by
      chemical analysis. On the other hand, evidence from histologic staining and
      electron microscopy demonstrates these tissue specimens have apparent difference
      in myelin content and microstructure.

PMID- 19859940
TI  - Quantitative CARS microscopic detection of analytes and their isotopomers in a
      two-channel microfluidic chip.

PMID- 19859941
TI  - Self-assembly of pH-switchable spiral tubes: supramolecular chemical springs.

PMID- 19859942
TI  - Nanoporous templates and membranes formed by nanosphere lithography and aluminum
      anodization.

PMID- 19859943
TI  - Flexible, transparent, conducting films of randomly stacked graphene from
      surfactant-stabilized, oxide-free graphene dispersions.
AB  - Graphite is exfoliated in water to give dispersions of mono- and few-layer
      graphene stabilized by surfactant. These dispersions can be used to form thin,
      disordered films of randomly stacked, oxide-free, few-layer graphenes. These
      films are transparent with a direct current conductivity of up to 1.5 x 10(4) S
      m(-1). The conductivity is stable under flexing for at least 2000 cycles. The
      electrical properties are limited by disorder and aggregation suggesting future
      routes for improvement.

PMID- 19859944
TI  - Force- and time-dependent feature size and shape control in molecular printing
      via polymer-pen lithography.

PMID- 19859945
TI  - Three-dimensional micro-MRI analysis of cerebral artery development in mouse
      embryos.
AB  - Vascular system development involves a complex, three-dimensional branching
      process that is critical for normal embryogenesis. In the brain, the arterial
      systems appear to develop in a stereotyped fashion, but no detailed quantitative
      analyses of the mouse embryonic cerebral arteries have been described. In this
      study, a gadolinium-based contrast perfusion method was developed to selectively
      enhance the cerebral arteries in fixed mouse embryos. Three-dimensional magnetic
      resonance micro-imaging (micro-MRI) data were acquired simultaneously from
      multiple embryos staged between 10 and 17 days of gestation, and a variety of
      image analysis methods was used to extract and analyze the cerebral arterial
      patterns. The results show that the primary arterial branches in the mouse brain
      are very similar between individuals, with the patterns established early and
      growth occurring by extension of the segments, while maintaining the underlying
      vascular geometry. To investigate the utility of this method for mutant mouse
      phenotype analysis, contrast-enhanced micro-MRI data were acquired from Gli2(-/-)
      mutant embryos and their wild-type littermates, showing several previously
      unreported vascular phenotypes in Gli2(-/-) embryos, including the complete
      absence of the basilar artery. These results demonstrate that contrast-enhanced
      micro-MRI provides a powerful tool for analyzing vascular phenotypes in a variety
      of genetically engineered mice.

PMID- 19859946
TI  - Characterizing healthy and diseased white matter using quantitative magnetization
      transfer and multicomponent T(2) relaxometry: A unified view via a four-pool
      model.
AB  - Nuclear magnetic resonance relaxation and magnetization transfer in cerebral
      white matter can be described using a four-pool model: two for water protons (in
      separate myelin and intra/extracellular compartments) and two for protons
      associated with the lipids and proteins of biologic membranes (of myelin and
      nonmyelin semisolids). This model was used to gain insight into the observations
      from multicomponent quantitative T(2) relaxometry and quantitative magnetization
      transfer imaging, both based on simplified white matter models and experimentally
      feasible in vivo. Using a set of coupled Bloch equations describing the behavior
      of the magnetization in a four-pool model of white matter, simulations of the
      quantitative T(2) relaxometry and quantitative magnetization transfer imaging
      techniques were performed. Pathology-inspired modifications were made to the four
      pool model to gauge their impact on quantitative T(2) relaxometry and
      quantitative magnetization transfer imaging observations. Our results show that
      changes in the rate of water movement between microanatomic compartments may
      impact otherwise stable quantitative T(2) relaxometry observations; that the
      measure of the quantitative magnetization transfer imaging-based semisolid pool
      population is robust, despite the presence of two distinct semisolid components;
      and that quantitative magnetization transfer imaging compartment size estimates
      are not influenced by changes in the T(2) of the intra/extracellular water pool.
      The four-pool model, while impractical for in vivo characterization, yields
      important insight into the interpretation of changes observed with these
      quantitative MRI methods based on simplified models of white matter.

PMID- 19859947
TI  - Classification of brain tumor type and grade using MRI texture and shape in a
      machine learning scheme.
AB  - The objective of this study is to investigate the use of pattern classification
      methods for distinguishing different types of brain tumors, such as primary
      gliomas from metastases, and also for grading of gliomas. The availability of an
      automated computer analysis tool that is more objective than human readers can
      potentially lead to more reliable and reproducible brain tumor diagnostic
      procedures. A computer-assisted classification method combining conventional MRI
      and perfusion MRI is developed and used for differential diagnosis. The proposed
      scheme consists of several steps including region-of-interest definition, feature
      extraction, feature selection, and classification. The extracted features include
      tumor shape and intensity characteristics, as well as rotation invariant texture
      features. Feature subset selection is performed using support vector machines
      with recursive feature elimination. The method was applied on a population of 102
      brain tumors histologically diagnosed as metastasis (24), meningiomas (4),
      gliomas World Health Organization grade II (22), gliomas World Health
      Organization grade III (18), and glioblastomas (34). The binary support vector
      machine classification accuracy, sensitivity, and specificity, assessed by leave
      one-out cross-validation, were, respectively, 85%, 87%, and 79% for
      discrimination of metastases from gliomas and 88%, 85%, and 96% for
      discrimination of high-grade (grades III and IV) from low-grade (grade II)
      neoplasms. Multiclass classification was also performed via a one-vs-all voting
      scheme.

PMID- 19859948
TI  - Viable tumor tissue detection in murine metastatic breast cancer by whole-body
      MRI and multispectral analysis.
AB  - Whole-body MRI combined with a semiautomated hierarchical multispectral image
      analysis technique was evaluated as a method for detecting viable tumor tissue in
      a murine model of metastatic breast cancer (4T1 cell line). Whole-body apparent
      diffusion coefficient, T(2), and proton density maps were acquired in this study.
      The viable tumor tissue segmentation included three-stage k-means clustering of
      the parametric maps, morphologic operations, application of a size threshold, and
      reader discrimination of the segmented objects. The segmentation results were
      validated by histologic evaluation, and the detection accuracy of the technique
      was evaluated at three size thresholds (15, 100, and 500 voxels). The accuracy
      was 88.9% for a 500-voxel size threshold, and the area under receiver operating
      characteristic curve was 0.84. The regions of segmented viable tumor tissue
      within the primary tumors were found mostly on the periphery of the tumors in
      agreement with the histologic findings. The presented technique was found capable
      of detecting metastases and segmenting the viable tumor from necrotic regions
      within tumors found in this model. It offers a noninvasive, whole-body, viable
      tumor tissue detection method for preclinical and potentially clinical
      applications such as tumor screening and evaluating therapeutic efficacy.

PMID- 19859949
TI  - Model-based blind estimation of kinetic parameters in dynamic contrast enhanced
      (DCE)-MRI.
AB  - A method to simultaneously estimate the arterial input function (AIF) and
      pharmacokinetic model parameters from dynamic contrast-enhanced (DCE)-MRI data
      was developed. This algorithm uses a parameterized functional form to model the
      AIF and k-means clustering to classify tissue time-concentration measurements
      into a set of characteristic curves. An iterative blind estimation algorithm
      alternately estimated parameters for the input function and the pharmacokinetic
      model. Computer simulations were used to investigate the algorithm's sensitivity
      to noise and initial estimates. In 12 patients with sarcomas, pharmacokinetic
      parameter estimates were compared with "truth" obtained from model regression
      using a measured AIF. When arterial voxels were included in the blind estimation
      algorithm, the resulting AIF was similar to the measured input function. The
      "true" K(trans) values in tumor regions were not significantly different than the
      estimated values, 0.99 +/- 0.41 and 0.86 +/- 0.40 min(-1), respectively, P =
      0.27. "True" k(ep) values also matched closely, 0.70 +/- 0.24 and 0.65 +/- 0.25
      min(-1), P = 0.08. When only tissue curves free of significant vascular
      contribution are used (v(p) < 0.05), the resulting AIF showed substantial delay
      and dispersion consistent with a more local AIF such as has been observed in
      dynamic susceptibility contrast imaging in the brain.

PMID- 19859950
TI  - Investigation and modeling of magnetization transfer effects in two-dimensional
      multislice turbo spin echo sequences with low constant or variable flip angles at
      3 T.
AB  - Magnetization transfer effects represent a major source of contrast in multislice
      turbo spin echo sequences (TSE)/fast spin echo sequences. Generally, low
      refocusing flip angles have become common in such MRI sequences, especially to
      mitigate specific absorption rate problems. Since the strength of magnetization
      transfer effects is related to the radiofrequency power and therefore specific
      absorption rate applied, magnetization transfer induced signal attenuations are
      investigated for a variety of TSE sequences with low constant and variable flip
      angles. Noticeable differences between the sequences have been observed. In
      particular, fewer signal attenuations are observed for TSE with low flip angles
      such as hyperecho-TSE and smooth transitions between pseudo steady states-TSE,
      leading to contrast that is less dependent on the number of slices. It is shown
      that the strength of the magnetization transfer-induced signal attenuations can
      be understood and described by a physical framework, which is based on the mean
      square flip angle of a given TSE sequence.

PMID- 19859951
TI  - IIR GRAPPA for parallel MR image reconstruction.
AB  - Accelerated parallel MRI has advantage in imaging speed, and its image quality
      has been improved continuously in recent years. This paper introduces a two
      dimensional infinite impulse response model of inverse filter to replace the
      finite impulse response model currently used in generalized autocalibrating
      partially parallel acquisitions class image reconstruction methods. The infinite
      impulse response model better characterizes the correlation of k-space data
      points and better approximates the perfect inversion of parallel imaging process,
      resulting in a novel generalized image reconstruction method for accelerated
      parallel MRI. This k-space-based reconstruction method includes the conventional
      generalized autocalibrating partially parallel acquisitions class methods as
      special cases and has a new infinite impulse response data estimation mechanism
      for effective improvement of image quality. The experiments on in vivo MRI data
      show that the proposed method significantly reduces reconstruction errors
      compared with the conventional two-dimensional generalized autocalibrating
      partially parallel acquisitions method, particularly at the high acceleration
      rates.

PMID- 19859952
TI  - Radial k-t FOCUSS for high-resolution cardiac cine MRI.
AB  - A compressed sensing dynamic MR technique called k-t FOCUSS (k-t FOCal
      Underdetermined System Solver) has been recently proposed. It outperforms the
      conventional k-t BLAST/SENSE (Broad-use Linear Acquisition Speed-up
      Technique/SENSitivity Encoding) technique by exploiting the sparsity of x-f
      signals. This paper applies this idea to radial trajectories for high-resolution
      cardiac cine imaging. Radial trajectories are more suitable for high-resolution
      dynamic MRI than Cartesian trajectories since there is smaller tradeoff between
      spatial resolution and number of views if streaking artifacts due to limited
      views can be resolved. As shown for Cartesian trajectories, k-t FOCUSS algorithm
      efficiently removes artifacts while preserving high temporal resolution. k-t
      FOCUSS algorithm applied to radial trajectories is expected to enhance dynamic
      MRI quality. Rather than using an explicit gridding method, which transforms
      radial k-space sampling data to Cartesian grid prior to applying k-t FOCUSS
      algorithms, we use implicit gridding during FOCUSS iterations to prevent k-space
      sampling errors from being propagated. In addition, motion estimation and motion
      compensation after the first FOCUSS iteration were used to further sparsify the
      residual image. By applying an additional k-t FOCUSS step to the residual image,
      improved resolution was achieved. In vivo experimental results show that this new
      method can provide high spatiotemporal resolution even from a very limited radial
      data set.

PMID- 19859953
TI  - 3D steady-state diffusion-weighted imaging with trajectory using radially batched
      internal navigator echoes (TURBINE).
AB  - While most diffusion-weighted imaging (DWI) is acquired using single-shot
      diffusion-weighted spin-echo echo-planar imaging, steady-state DWI is an
      alternative method with the potential to achieve higher-resolution images with
      less distortion. Steady-state DWI is, however, best suited to a segmented three
      dimensional acquisition and thus requires three-dimensional navigation to fully
      correct for motion artifacts. In this paper, a method for three-dimensional
      motion-corrected steady-state DWI is presented. The method uses a unique
      acquisition and reconstruction scheme named trajectory using radially batched
      internal navigator echoes (TURBINE). Steady-state DWI with TURBINE uses slab
      selection and a short echo-planar imaging (EPI) readout each pulse repetition
      time. Successive EPI readouts are rotated about the phase-encode axis. For image
      reconstruction, batches of cardiac-synchronized readouts are used to form three
      dimensional navigators from a fully sampled central k-space cylinder. In vivo
      steady-state DWI with TURBINE is demonstrated in human brain. Motion artifacts
      are corrected using refocusing reconstruction and TURBINE images prove less
      distorted compared to two-dimensional single-shot diffusion-weighted-spin-EPI.

PMID- 19859954
TI  - Balloon angioplasty versus stenting with nitinol stents in intermediate length
      superficial femoral artery lesions.
AB  - BACKGROUND: Recent randomized trials investigating stent implantation compared
      with balloon angioplasty for treatment of superficial femoral artery (SFA)
      disease have given divergent results in short (mean 5 cm) and intermediate (mean
      10 cm) lesions. We reinvestigated whether primary nitinol stenting is associated
      with a morphologic and clinical benefit when compared with percutaneous
      transluminal angioplasty with optional stenting (PTA) in intermediate-length
      lesions. METHODS: We randomly assigned 73 patients with severe claudication or
      chronic limb ischemia and average 8 cm long (range 3-20 cm) SFA stenosis or
      occlusion to primary stent implantation (n = 34) or PTA (n = 39). Restenosis >50%
      and clinical outcome were assessed at 3, 6, and 12 months postintervention.
      RESULTS: Average length of the treated segments was 98 + or - 54 mm and 71 + or -
      43 mm in the stent and PTA groups (P = 0.011), respectively. In the PTA group,
      secondary stenting was performed in 10 of 39 patients (26%) due to a suboptimal
      result after balloon dilation. Restenosis rates in the stent and PTA groups were
      21.9% versus 55.6% (P = 0.005) at 6 months by CT-angiography, and 2.9% versus
      18.9% (P = 0.033), 18.2% versus 50.0% (P = 0.006), and 34.4% versus 61.1% (P =
      0.028) at 3, 6, and 12 months by sonography, respectively. Clinically, patients
      in the stent group reported a significantly higher maximum walking capacity
      compared with the PTA group at 6 and 12 months. CONCLUSION: In this randomized
      multicenter trial, primary stenting with a self-expanding nitinol stent for
      treatment of intermediate length SFA disease resulted morphologically and
      clinically superior midterm results compared with balloon angioplasty with
      optional secondary stenting.

PMID- 19859955
TI  - Tailored RF pulse for magnetization inversion at ultrahigh field.
AB  - The radiofrequency (RF) transmit field is severely inhomogeneous at ultrahigh
      field due to both RF penetration and RF coil design issues. This particularly
      impairs image quality for sequences that use inversion pulses such as
      magnetization prepared rapid acquisition gradient echo and limits the use of
      quantitative arterial spin labeling sequences such as flow-attenuated inversion
      recovery. Here we have used a search algorithm to produce inversion pulses
      tailored to take into account the heterogeneity of the RF transmit field at 7 T.
      This created a slice selective inversion pulse that worked well (good slice
      profile and uniform inversion) over the range of RF amplitudes typically obtained
      in the head at 7 T while still maintaining an experimentally achievable pulse
      length and pulse amplitude in the brain at 7 T. The pulses used were based on the
      frequency offset correction inversion technique, as well as time dilation of
      functions, but the RF amplitude, frequency sweep, and gradient functions were all
      generated using a genetic algorithm with an evaluation function that took into
      account both the desired inversion profile and the transmit field inhomogeneity.

PMID- 19859957
TI  - Optimization of k-space trajectories for compressed sensing by Bayesian
      experimental design.
AB  - The optimization of k-space sampling for nonlinear sparse MRI reconstruction is
      phrased as a Bayesian experimental design problem. Bayesian inference is
      approximated by a novel relaxation to standard signal processing primitives,
      resulting in an efficient optimization algorithm for Cartesian and spiral
      trajectories. On clinical resolution brain image data from a Siemens 3T scanner,
      automatically optimized trajectories lead to significantly improved images,
      compared to standard low-pass, equispaced, or variable density randomized
      designs. Insights into the nonlinear design optimization problem for MRI are
      given.

PMID- 19859956
TI  - Robust water/fat separation in the presence of large field inhomogeneities using
      a graph cut algorithm.
AB  - Water/fat separation is a classical problem for in vivo proton MRI. Although many
      methods have been proposed to address this problem, robust water/fat separation
      remains a challenge, especially in the presence of large amplitude of static
      field inhomogeneities. This problem is challenging because of the nonuniqueness
      of the solution for an isolated voxel. This paper tackles the problem using a
      statistically motivated formulation that jointly estimates the complete field map
      and the entire water/fat images. This formulation results in a difficult
      optimization problem that is solved effectively using a novel graph cut
      algorithm, based on an iterative process where all voxels are updated
      simultaneously. The proposed method has good theoretical properties, as well as
      an efficient implementation. Simulations and in vivo results are shown to
      highlight the properties of the proposed method and compare it to previous
      approaches. Twenty-five cardiac datasets acquired on a short, wide-bore scanner
      with different slice orientations were used to test the proposed method, which
      produced robust water/fat separation for these challenging datasets. This paper
      also shows example applications of the proposed method, such as the
      characterization of intramyocardial fat.

PMID- 19859958
TI  - Five-year clinical follow-up after implantation of the Endeavor zotarolimus
      eluting stent: ENDEAVOR I, first-in-human study.
AB  - OBJECTIVE: To evaluate the 5-year clinical outcomes of patients treated with the
      Endeavor zotarolimus-eluting stent (ZES) in the ENDEAVOR I first-in-human study.
      BACKGROUND: ENDEAVOR I was a prospective, nonrandomized, multicenter study of the
      Endeavor ZES in 100 consecutive patients with symptomatic coronary artery disease
      (CAD) due to de novo, stenotic lesions in native coronary arteries. METHODS:
      Patients with single or multivessel CAD were eligible to participate, but only
      one lesion per patient was treated. The lesion had to have > or = 50% stenosis,
      be < or = 15 mm in length, and located in a vessel with a reference diameter of
      3.0-3.5 mm. Major adverse cardiac events (MACE), target lesion revascularization
      (TLR), target vessel failure (TVF), and stent thrombosis were evaluated 5 years
      after stent implantation. RESULTS: The cumulative incidence of MACE was 2.0% at 1
      year, 3.0% at 2 years, 6.1% at 3 years, 7.2% at 4 years, and 7.2% at 5 years. At
      5 years, there were seven patients who had eight events; four noncardiac (cancer)
      deaths, three cases of TLR, of which one presented as a non-Q-wave MI because of
      a stent thrombosis at 10 days after the index procedure. There were no late or
      very late stent thromboses by any definition. TVF at 5 years was 5.2%.
      CONCLUSIONS: Use of the Endeavor ZES to treat symptomatic CAD due to de novo
      lesions in native coronary arteries resulted in sustained clinical benefits to 5
      years, with low rates of MACE, TLR, TVF, and stent thrombosis.

PMID- 19859959
TI  - Percutaneous versus surgical delivery of autologous myoblasts after chronic
      myocardial infarction: an in vivo cardiovascular magnetic resonance study.
AB  - BACKGROUND: Stem cell transplantation for chronic myocardial infarction (MI)
      provides variable benefits. Most clinical trials have relied on surgical
      delivery, where results are biased by simultaneous coronary bypass. When bypass
      is not indicated, percutaneous delivery may provide comparable efficacy with
      reduced risk. We evaluated in vivo by cardiovascular magnetic resonance (CMR) the
      effects of autologous myoblast (AM) transplantation on myocardial morphology,
      function, perfusion and scar, and compared percutaneous versus surgical delivery.
      METHODS: Chronic MI was completed in 10 Yucatan mini-pigs. Three months later, AM
      were injected in half by percutaneous NOGA(R) system and in the other half by
      surgical mini-thoracotomy. CMR was performed at baseline and 6 months after
      transplantation. RESULTS: Six months after injection, AM transplantation led to a
      26.3% decrease in indexed left ventricular end-diastolic volume (95% CI: 20.1
      29.7%; P = 0.02), 25.5% thickening of the infarct-related segment (IRS) wall (95%
      CI: 19.6-33.2%; P = 0.03), and 20.9% increase in left ventricle (LV) ejection
      fraction (95% CI: 15.8-28.4%; P = 0.03). Scar tissue within IRS decreased by
      29.4% (95% CI: 19.2-37.0%; P = 0.03), whereas the number of nonviable segments
      decreased by 25.0% (95% CI: 16.4-32.6%; P = 0.04). Myocardial perfusion of IRS
      improved by 29.1% (95% CI: 19.7-36.1%; P = 0.04). The arrhythmogenic peri-infarct
      zone increased by 33.2% (95% CI: 21.4-44.1%; P = 0.01) after AM transplantation.
      Benefits were similar by percutaneous or by surgical delivery. CONCLUSIONS:
      Comprehensive in vivo CMR reveals reversed remodeling and improved systolic
      function, perfusion, and scar characteristics after AM transplantation. A
      relative increase in the arrhythmogenic peri-infarct border zone may explain
      previously reported arrhythmia. Percutaneous and surgical transplantation of AM
      both lead to comparable improvements in chronic MI.

PMID- 19859960
TI  - T2 measurement in articular cartilage: impact of the fitting method on accuracy
      and precision at low SNR.
AB  - T2 relaxation time is a promising MRI parameter for the detection of cartilage
      degeneration in osteoarthritis. However, the accuracy and precision of the
      measured T2 may be substantially impaired by the low signal-to-noise ratio of
      images available from clinical examinations. The purpose of this work was to
      assess the accuracy and precision of the traditional fit methods (linear least
      squares regression and nonlinear fit to an exponential) and two new noise
      corrected fit methods: fit to a noise-corrected exponential and fit of the noise
      corrected squared signal intensity to an exponential. Accuracy and precision have
      been analyzed in simulations, in phantom measurements, and in seven repetitive
      acquisitions of the patellar cartilage in six healthy volunteers. Traditional fit
      methods lead to a poor accuracy for low T2, with overestimations of the exact T2
      up to 500%. The noise-corrected fit methods demonstrate a very good accuracy for
      all T2 values and signal-to-noise ratio. Even more, the fit to a noise-corrected
      exponential results in precisions comparable to the best achievable precisions
      (Cramer-Rao lower bound). For in vivo images, the traditional fit methods
      considerably overestimate T2 near the bone-cartilage interface. Therefore, using
      an adequate fit method may substantially improve the sensitivity of T2 to detect
      pathology in cartilage and change in T2 follow-up examinations.

PMID- 19859961
TI  - High-resolution uniform MR imaging of finger joints using a dedicated RF coil at
      3T.
AB  - PURPOSE: To develop a dedicated radiofrequency (RF) coil for high-resolution
      magnetic resonance imaging (MRI) of finger joints at 3T to improve diagnostic
      evaluation of arthritic diseases. MATERIALS AND METHODS: A dedicated cylindrical
      RF receive coil was developed for imaging finger joints at 3T. A planar coil, a
      saddle coil, and a 1.5T coil with similar design as the dedicated coil were also
      constructed to compare imaging performance with the dedicated coil. A phantom was
      used for quantitative evaluation. Three-dimensional images were obtained on four
      subjects and a cadaver finger specimen using isotropic resolution of 160 mum in
      9:32 minutes. The images were reviewed by two musculoskeletal radiologists.
      RESULTS: The dedicated finger coil provided higher signal-to-noise and greater
      signal uniformity than the other coils. It supported high-resolution imaging that
      demonstrated anatomical details of the entire finger joint, and in the subject
      study revealed abnormalities not detectable by traditional clinical resolution.
      CONCLUSION: The dedicated finger coil optimizes the potential advantages of 3T
      scanners compared to lower field magnets. Use of this coil should facilitate
      early diagnosis, improve assessment of treatment response, and provide better
      understanding of basic mechanisms that underlie arthritis.

PMID- 19859962
TI  - Recurrent systemic infections with Streptococcus pneumoniae do not aggravate the
      course of experimental neurodegenerative diseases.
AB  - Neurological symptoms of patients suffering from neurodegenerative diseases such
      as Alzheimer's dementia (AD), Parkinson's disease (PD), or amyotrophic lateral
      sclerosis (ALS) often worsen during infections. We assessed the disease
      modulating effects of recurrent systemic infections with the most frequent
      respiratory pathogen, Streptococcus pneumoniae, on the course of AD, PD, and ALS
      in mouse models of these neurodegenerative diseases [transgenic Tg2576 mice,
      (Thy1)-[A30P]alpha SYN mice, and Tg(SOD1-G93A) mice]. Mice were repeatedly
      challenged intraperitoneally with live S. pneumoniae type 3 and treated with
      ceftriaxone for 3 days. Infection caused an increase of interleukin-6
      concentrations in brain homogenates. The clinical status of (Thy1)-[A30P]alpha
      SYN mice and Tg(SOD1-G93A) mice was monitored by repeated assessment with a
      clinical score. Motor performance was controlled by the tightrope test and the
      rotarod test. In Tg2576 mice, spatial memory and learning deficits were assessed
      in the Morris water maze. In none of the three mouse models onset or course of
      the disease as evaluated by the clinical tests was affected by the recurrent
      systemic infections performed. Levels of alpha-synuclein in brains of (Thy1)
      [A30P]alpha SYN mice did not differ between infected animals and control animals.
      Plaque sizes and concentrations of A beta 1-40 and A beta 1-42 were not
      significantly different in brains of infected and uninfected Tg2576 mice. In
      conclusion, onset and course of disease in mouse models of three common
      neurodegenerative disorders were not influenced by repeated systemic infections
      with S. pneumoniae, indicating that the effect of moderately severe acute
      infections on the course of neurodegenerative diseases may be less pronounced
      than suspected.

PMID- 19859964
TI  - Caspase inhibition by cardiotrophin-1 prevents neuronal death in vivo and in
      vitro.
AB  - Our previous studies showed that cardiotrophin-1 (CT-1), a cytokine in the
      interleukin-6 family, protected the developing rat brain against focal cerebral
      ischemia (FCI) in vivo and prevented cortical neuron death in vitro. However, the
      mechanisms by which CT-1 prevents neuronal death are not clearly understood. This
      in vivo study focused on whether CT-1 treatment prevented FCI-induced brain
      injuries in the postnatal day 7 (P7) rat through modulating activation of the
      initiator caspase-8 (C-8) and the downstream effector caspase-3 (C-3). FCI caused
      a significant increase in expressions of cleaved C-8 and C-3 and, meanwhile, a
      significant decrease in expression of microtubule-associated protein-2 (MAP2) in
      the left ischemic cortex of the P7 rat brain after FCI. Exogenous treatment of CT
      1 significantly reduced the expression of cleaved C-8 or C-3 and attenuated the
      decline in MAP2 expression in the ischemic cortex from 12 to 24 hr after FCI.
      Subsequent in vitro experiments demonstrated that CT-1 treatment inhibited sodium
      nitroprusside (SNP)-induced activation of C-8 and C-3 and loss of MAP2-positive
      neurons in cortical neuron cultures. More importantly, CT-1 activated several
      pathways, including Janus kinase 2, signal transducers and activators of
      transcription 3, nuclear factor kappa B, mitogen-activated protein kinase (MAPK),
      and MAPK kinase in the cultures exposed to SNP. This is the first suggestion that
      CT-1 prevents neuronal injury in the developing central nervous system possibly
      through mediating multiple signal pathways, inhibiting activation of C-8 and C-3.

PMID- 19859963
TI  - Axon responses of embryonic stem cell-derived dopaminergic neurons to semaphorins
      3A and 3C.
AB  - Class 3 Semaphorins are a subfamily of chemotropic molecules implicated in the
      projection of dopaminergic neurons from the ventral mesencephalon and in the
      formation of the nigrostriatal pathway (NSP) during embryonic development. In
      humans, loss of mesencephalic dopaminergic neurons leads to Parkinson's disease
      (PD). Cell replacement therapy with dopaminergic neurons generated from embryonic
      stem cells (ES-TH(+)) is being actively explored in models of PD. Among several
      requisites for this approach to work are adequate reconstruction of the NSP and
      correct innervation of normal striatal targets by dopaminergic axons. In this
      work, we characterized the response of ES-TH(+) neurons to semaphorins 3A, 3C,
      and 3F and compared it with that of tyrosine hidroxylase-positive neurons (TH(+))
      obtained from embryonic ventral mesencephalon (VM-TH(+)). We observed that
      similar proportions of ES-TH(+) and VM-TH(+) neurons express semaphorin receptors
      neuropilins 1 and 2. Furthermore, the axons of both populations responded very
      similarly to semaphorin exposure: semaphorin 3A increased axon length, and
      semaphorin 3C attracted axons and increased their length. These effects were
      mediated by neuropilins, insofar as addition of blocking antibodies against these
      proteins reduced the effects on axonal growth and attraction, and only TH(+)
      axons expressing neuropilins responded to the semaphorins analyzed. The
      observations reported here show phenotypic similarities between VM-TH(+) and ES
      TH(+) neurons and suggest that semaphorins 3A and 3C could be employed to guide
      axons of grafted ES-TH(+) in therapeutic protocols for PD.

PMID- 19859965
TI  - DHA diet reduces AD pathology in young APPswe/PS1 Delta E9 transgenic mice:
      possible gender effects.
AB  - Epidemiological and clinical trial findings suggest that consumption of
      docosahexaenoic acid (DHA) lowers the risk of Alzheimer's disease (AD). We
      examined the effects of short-term (3 months) DHA enriched diet on plaque
      deposition and synaptic defects in forebrain of young APPswe/PS1 Delta E9
      transgenic (tg) and non-transgenic (ntg) mice. Gas chromatography revealed a
      significant increase in DHA concomitant with a decrease of arachidonic acid in
      both brain and liver in mice fed with DHA. Female tg mice consumed relatively
      more food daily than ntg female mice, independent of diet. Plaque load was
      significantly reduced in the cortex, ventral hippocampus and striatum of female
      APPswe/PS1 Delta E9 tg mice on DHA diet compared to female tg mice on control
      diet. Immunoblot quantitation of the APOE receptor, LR11, which is involved in
      APP trafficking and A beta production, were unchanged in mice on DHA or control
      diets. Moreover drebrin levels were significantly increased in the hippocampus of
      tg mice on the DHA diet. Finally, in vitro DHA treatment prevented amyloid
      toxicity in cell cultures. Our findings support the concept that increased DHA
      consumption may play and important role in reducing brain insults in female AD
      patients.

PMID- 19859966
TI  - Activity-dependent somatostatin gene expression is regulated by cAMP-dependent
      protein kinase and Ca2+-calmodulin kinase pathways.
AB  - Ca(2+) influx through L-type voltage-gated Ca(2+) channels (L-VSCC) is required
      for K(+)-induced somatostatin (SS) mRNA. Increase in intracellular Ca(2+)
      concentration leads to the activation of cyclic AMP-responsive element binding
      protein (CREB), a key regulator of SS gene transcription. Several different
      protein kinases possess the capability of driving CREB upon membrane
      depolarization. We investigated which of the signalling pathways involved in CREB
      activation mediates SS gene induction in response to membrane depolarization in
      cerebrocortical cells exposed to 56 mM K(+). Activity dependent phosphorylation
      of CREB in Ser(133) was immunodetected. Activation of CREB was biphasic showing
      two peaks at 5 and 60 min. The selective inhibitors of extracellular signal
      related protein kinase/mitogen-activated protein kinase (ERK/MAPK) PD098059,
      cyclic-AMPdependent protein kinase (cAMP/PKA) H89 and RpcAMPS, and
      Ca(2+)/calmodulin-dependent protein kinases (CaMKs) pathways KN62 and KN93 were
      used to determine the signalling pathways involved in CREB activation. Here we
      show that the early activation of CREB was dependent on cAMP/PKA along with CaMKs
      pathways whereas the ERK/MAPK and CaMKs were implicated in the second peak. We
      observed that H89, RpcAMPS, KN62 and KN93 blocked K(+)-induced SS mRNA whereas
      PD098059 did not. These findings indicate that K(+)-induced SSmRNA is mediated by
      the activation of cAMP/PKA and CaMKs pathways, thus suggesting that the early
      activation of CREB is involved in the induction of SS by neuronal activity. We
      also demonstrated, using transient transfections of cerebrocortical cells, that
      K(+) induces the transcriptional regulation of the SS gene through the cAMP
      responsive element (CRE) sequence located in the SS promoter.

PMID- 19859967
TI  - Cellular expression pattern of the protease-activated receptor 4 in the
      hippocampus in naive rats and after global ischaemia.
AB  - A pronounced hippocampal expression of the Protease-activated Receptor 4 (PAR4)
      has recently been shown. In the current study the authors define the PAR4
      associated sub-cellular structures and the influence of global ischaemia on the
      expression of PAR4. For that purpose the authors performed double labelling with
      fluorescence immunohistochemistry on tissue from naive and post-ischaemic rats.
      In naive animals - apart from the expression in granular and pyramidal neurons -
      there was an intensive lamellar expression of PAR4 in the CA4 region. Further
      analysis revealed that PAR4 was localised exclusively on mossy fibre axons in CA4
      as detected by double-labelling with calbindin D-28k, but there was no overlap
      with markers of the neuronal cell body, interneurons, and post-synaptic, pre
      synaptic and dendritic structures. Three and 14 days post ischaemia, CA1 neurons
      were degenerated and, consequently, there was no PAR4 signal in the CA1 band. In
      most other hippocampal structures no change in the PAR4 expression was
      detectable, with the exception of the CA3 region. Here, the fibre-associated PAR4
      signal was diminished and disintegrated post ischaemia. Additionally, a
      redistribution from the membrane-bound neuronal localisation of PAR4 in control
      animals to a diffuse localisation all over the cell soma was revealed in the CA3
      area 14 days post ischaemia. In conclusion, the current study proves for the
      first time that PAR4 is localised in mossy fibre axons. The altered expression in
      CA3 neurons after ischaemia indicates that PAR4 may be involved in post-ischaemic
      adaptive mechanisms.

PMID- 19859968
TI  - Synaptic localization of neuroligin 2 in the rodent retina: comparative study
      with the dystroglycan-containing complex.
AB  - Several recent studies have shown that neuroligin 2 (NL2), a component of the
      cell adhesion neurexins-neuroligins complex, is localized postsynaptically at
      hippocampal and other inhibitory synapses throughout the brain. Other studies
      have shown that components of the dystroglycan complex are also localized at a
      subset of inhibitory synapses and are coexpressed with NL2 in brain. These data
      prompted us to undertake a comparative study between the localization of NL2 and
      the dystroglycan complex in the rodent retina. First, we determined that NL2 mRNA
      is expressed both in the inner and in the outer nuclear layers. Second, we found
      that NL2 is localized both in the inner and in the outer synaptic plexiform
      layers. In the latter, the horseshoe-shaped pattern of NL2 and its extensive
      colocalization with RIM2, a component of the presynaptic active zone at ribbon
      synapses, argue that NL2 is localized presynaptically at photoreceptor terminals.
      Third, comparison of NL2 and the dystroglycan complex distribution patterns
      reveals that, despite their coexpression in the outer plexiform layer, they are
      spatially segregated within distinct domains of the photoreceptor terminals,
      where NL2 is selectively associated with the active zone and the dystroglycan
      complex is distally distributed in the lateral regions. Finally, we report that
      the dystroglycan deficiency in the mdx(3cv) mouse does not alter NL2 localization
      in the outer plexiform layer. These data show that the NL2- and dystroglycan
      containing complexes are differentially localized in the presynaptic
      photoreceptor terminals and suggest that they may serve distinct functions in
      retina.

PMID- 19859970
TI  - Myoepithelial carcinoma of the parotid gland metastatic to the kidney: case
      report and review of the literature.
AB  - Myoepithelial carcinoma is a rare locally aggressive malignant neoplasm of the
      salivary glands. The tumor is composed almost exclusively of tumor cells with
      myoepithelial differentiation and characterized by infiltrative growth and
      potential for distant metastasis. Tumor cells often display morphologic
      heterogeneity with a wide range of cytomorphologic features, such as epithelioid,
      plasmacytoid, spindle, and clear cell types, making its recognition challenging.
      Only limited reports on its metastatic behavior are available in the literature.
      We describe a case of metastatic myoepithelial carcinoma of the kidney from the
      parotid gland diagnosed by computed tomography guided fine-needle aspiration
      biopsy. Immunochemical studies are important to confirm myoepithelial
      differentiation of the tumor cells. Knowledge of the clinical history,
      radiographic characterization, and morphological correlation with the primary
      tumor are emphasized.

PMID- 19859969
TI  - Superparamagnetic iron oxide nanoparticles as a dual imaging probe for targeting
      hepatocytes in vivo.
AB  - Hepatocyte-specific targeting agents are useful for evaluation of the hepatocytic
      function and the monitoring of disease progress. Superparamagnetic iron oxide
      nanoparticles (SPION) bearing terminal galactose groups exhibit a high affinity
      for the asialoglycoprotein receptor on the hepatocyte surface. In this study, we
      synthesized and characterized the dual probe SPION detectable by both nuclear and
      MR imaging modality for specifically targeting hepatocytes in vivo. SPION with 12
      nm diameter were functionalized with dopamine. Surface modification of the SPION
      was performed to target asialoglycoprotein receptor on hepatocytes, using
      lactobionic acid. Transmission electron microscope images demonstrated that SPION
      displayed highly uniform characteristics in terms of both particle size and
      shape. The X-ray diffraction pattern of SPION revealed a nanocrystal structure of
      magnetite. To radiolabel the magnetite with (99m)Tc,
      diethylenetriaminepentaacetic acid was conjugated to unreacted functional groups
      of dopamine. (99m)Tc-labeled lactobionic acid-SPION showed high accumulation in
      liver, with 38.43 +/- 6.45% injected dose per gram. In MR imaging, the reduction
      of the T(2) signal in the liver by lactobionic acid-SPION was approximately 50.8
      +/- 7.3%. Competition studies and transmission electron microscope images of
      liver tissues demonstrated that the lactobionic acid-SPION were localized in
      hepatocytes. Therefore, the lactobionic acid-SPION may be used as a hepatocyte
      targeted dual contrast agent for both nuclear and MR imaging.

PMID- 19859971
TI  - Modified fine-needle aspiration technique for diagnosis of granulomatous skin
      lesions with special reference to leprosy and cutaneous tuberculosis.
AB  - Skin infections are commonly assessed by slit skin or scrape methods. Fine-needle
      aspiration biopsy (FNAB) is highly effective especially with blanching of skin to
      ensure good yield and reduced bleeding. The aim of this study was to assess
      usefulness of cytology, especially modified FNAB technique, in diagnosis of
      leprosy and cutaneous tuberculosis and to identify specific cytological
      characteristics for diagnosis and classification. The study was conducted on 40
      patients-25 cases of leprosy and 15 cases of cutaneous tuberculosis. Smears were
      prepared using modified FNAB technique, slit skin, and scrape methods (depending
      on type of lesion). Cytological diagnosis was confirmed by histopathology where
      the Ridley-Jopling system was used to classify cases of leprosy. A similar
      attempt was made for diagnosis and classification of leprosy on cytology.
      Diagnoses rendered by both modalities were compared to assess the efficacy of
      cytological examination. Cytological diagnosis was made in 23 cases of leprosy
      and 12 cases of cutaneous tuberculosis. The smears showed good cellularity. A
      broad division into tuberculoid and lepromatous leprosy could be made fairly
      accurately on cytology. Maximum agreement among clinical, cytological, and
      histopathological diagnosis was observed in cases of tuberculoid leprosy. Smears
      of cutaneous tuberculosis were characterized by epithelioid cell granulomas with
      caseation. Overall accuracy of diagnosis was 92% in leprosy and 80% in
      tuberculosis. FNAB is an inexpensive and accurate procedure for diagnosis of
      leprosy and cutaneous tuberculosis. The modified technique yields good results.
      However, clinical correlation, acid-fast staining, and culture are essential as
      they provide valuable supportive information.

PMID- 19859972
TI  - Simultaneous Chlamydia trachomatis and HPV infection in pregnant women.
AB  - Pregnancy is associated with HPV infection and with Chlamydia trachomatis (CT)
      infection mostly due to the natural immunosuppression. In addition, pregnancy
      associated to CT infection can lead to adverse conditions to the woman and fetus,
      and CT is also believed to be a co-factor in human immunodeficiency virus
      infection and HPV-induced cervical cancer. The aim of this study was to establish
      the odds ratios (OR) of CT infection in to HPV-infected pregnant women and vice
      versa of women stratified by age (<25 years) and marital status. This work is
      part of a national multicentric transversal study carried out in six Brazilian
      cities supported by the Ministry of Health of Federal Government of Brazil in
      2003. Cervical scrapes of 371 pregnant women were sampled. We performed a hybrid
      capture-2 technique to diagnose these samples on HPV and CT infection, and the
      women responded a questionnaire. Significant association was observed between
      nonstable marital status and hr-HPV infection [OR = 2.61 (1.38-4.97) P = 0.003)],
      and age <25 years old [OR = 2.26 (1.09-4.71) P = 0.029]. Nonstable marital status
      was also associated with lr-HPV infection [OR = 2.67 (1.59-4.50) P < 0.001), and
      age <25 years old [OR = 2.55 (1.51-4.32) P < 0.001). Fifty of the 371 pregnant
      women were infected with hr-HPV (13.5%) and 111 (30.0%) were infected with lr
      HPV. The coinfections of HPV and CT were found in 31 women, that is, 8.36% of the
      pregnant women (P < 0.001). The high rate of simultaneous CT and HPV infection in
      pregnant women favors the recommendation to screen pregnant women for both CT and
      HPV.

PMID- 19859973
TI  - Polysaccharide-based vaccine delivery systems: Macromolecular assembly,
      interactions with antigen presenting cells, and in vivo immunomonitoring.
AB  - Using a strategy of macromolecular assembly, a colloidal vaccine delivery system
      was obtained from chitosan and dextran sulfate and loaded with an antigenic
      protein (p24, the capsid protein of HIV-1). The colloidal polyelectrolyte
      complexes (PECs) were obtained by charge neutralization of the polyanion and
      polycation at a charge ratio (n(+)/n(-)) of 2 (CHDS). The conditions of assembly
      were tuned to maintain the colloidal properties of the carrier in high salt
      environment. The relative molar masses of the two polyions and the degree of
      acetylation (DA) of chitosan were essential parameters to achieve this goal, and
      this could be related to the nanometric scale organization of the colloids
      observed by Small Angle X-rays Scattering experiments. The binding of p24 to the
      colloidal carrier was achieved and the release of the antigen was investigated.
      Antigen presenting cells [dendritic cells (DCs)], obtained from monocytes, could
      internalize the colloids. Immature DCs (iDCs) were not matured by the colloidal
      PECs either loaded or not loaded with p24, as proved by Fluorescent Activated
      Cell Sorting (FACS) analysis. Despite this lack of in vitro interaction, a
      specific immune response was observed in mice with a high production of
      antibodies, after subcutaneous injection. The analysis of the interleukin
      production shows that both the cellular and the humoral responses were
      stimulated. This work brings a physico-chemical insight on polysaccharide-based
      antigen delivery systems and opens up new perspectives for their use as vaccine
      carriers.

PMID- 19859974
TI  - Robust GRAPPA-accelerated diffusion-weighted readout-segmented (RS)-EPI.
AB  - Readout segmentation (RS-EPI) has been suggested as a promising variant to echo
      planar imaging (EPI) for high-resolution imaging, particularly when combined with
      parallel imaging. This work details some of the technical aspects of diffusion
      weighted (DW)-RS-EPI, outlining a set of reconstruction methods and imaging
      parameters that can both minimize the scan time and afford high-resolution
      diffusion imaging with reduced distortions. These methods include an efficient
      generalized autocalibrating partially parallel acquisition (GRAPPA) calibration
      for DW-RS-EPI data without scan time penalty, together with a variant for the
      phase correction of partial Fourier RS-EPI data. In addition, the role of
      pulsatile and rigid-body brain motion in DW-RS-EPI was assessed. Corrupt DW-RS
      EPI data arising from pulsatile nonlinear brain motion had a prevalence of
      approximately 7% and were robustly identified via k-space entropy metrics. For DW
      RS-EPI data corrupted by rigid-body motion, we showed that no blind overlap was
      required. The robustness of RS-EPI toward phase errors and motion, together with
      its minimized distortions compared with EPI, enables the acquisition of exquisite
      3 T DW images with matrix sizes close to 512(2).

PMID- 19859975
TI  - PGC-1alpha activation as a therapeutic approach in mitochondrial disease.
AB  - Mitochondria play a central role in cellular homeostasis. Hence, mitochondrial
      dysfunction resulting in impaired ATP supply is detrimental to cell viability and
      causes severe and often fatal disorders. Current treatment of these mitochondrial
      disorders is limited and mostly addresses the symptoms, but not the deficiency
      itself. Recent work in cell and animal models of mitochondrial disease shows that
      increased mitochondrial biogenesis can boost residual OXPHOS capacity and thereby
      prevent the bioenergetic crisis. In animal models, this strategy results in
      increased health and lifespan. Here, I review which mitochondrial processes are
      affected in known mitochondrial disorders and discuss why PGC-1alpha mediated
      mitochondrial biogenesis offers a promising venue for treatment of mitochondrial
      disorders.

PMID- 19859976
TI  - Methionine gamma-lyase: the unique reaction mechanism, physiological roles, and
      therapeutic applications against infectious diseases and cancers.
AB  - Sulfur-containing amino acids (SAAs) are essential components in many biological
      processes and ubiquitously distributed to all organisms. Both biosynthetic and
      catabolic pathways of SAAs are heterogeneous among organisms and between
      developmental stages, and regulated by the environmental changes. Limited lineage
      of organisms ranging from archaea to plants, but not human, possess a unique
      enzyme methionine gamma-lyase (MGL, EC 4.4.1.11) to directly degrade SAA to alpha
      keto acids, ammonia, and volatile thiols. The reaction mechanisms and the
      physiological roles of this enzyme are partially demonstrated by the
      enzymological analyzes, structure determination, isotopic labeling of the
      intermediate metabolites, and functional analyzes of deficient mutants. MGL has
      been exploited as a drug target for the infectious diseases caused by parasitic
      protozoa and anaerobic periodontal bacteria. In addition, MGL has been utilized
      to develop therapeutic interventions of various cancers, by introducing
      recombinant proteins to deplete methionine essential for the growth of cancer
      cells. In this review, we discuss the current understanding of enzymological
      properties, putative physiological roles, and therapeutic applications of MGL.

PMID- 19859977
TI  - Fluorescent proteins for live cell imaging: opportunities, limitations, and
      challenges.
AB  - The green fluorescent protein (GFP) from the jellyfish Aequorea victoria can be
      used as a genetically encoded fluorescence marker due to its autocatalytic
      formation of the chromophore. In recent years, numerous GFP-like proteins with
      emission colors ranging from cyan to red were discovered in marine organisms.
      Their diverse molecular properties enabled novel approaches in live cell imaging
      but also impose certain limitations on their applicability as markers. In this
      review, we give an overview of key structural and functional properties of
      fluorescent proteins that should be considered when selecting a marker protein
      for a particular application and also discuss challenges that lie ahead in the
      further optimization of the glowing probes.

PMID- 19859978
TI  - Fabry disease: treatment and diagnosis.
AB  - Fabry disease is an X-linked lysosomal disorder that results from a deficiency of
      the lysosomal enzyme alpha-galactosidase A leading to accumulation of
      glycolipids, mainly globotriaosylceramide in the cells from different tissues.
      Classical Fabry disease affects various organs. Clinical manifestations start at
      early age and include angiokeratoma, acroparesthesia, hypohydrosis, heat/exercise
      intolerance, gastrointestinal pain, diarrhea, and fever. The main complications
      of Fabry disease are more prominent after the age of 30 when kidney, heart,
      and/or cerebrovascular disorders appear. Most of the heterozygous females are
      symptomatic. Enzyme replacement therapy (ERT) is the only specific treatment for
      Fabry disease. The beneficial effect of ERT on different organs/systems has been
      extensively evaluated. Quality of life of patients receiving ERT is improved.
      Enzyme replacement stabilizes or slows the decline in renal function and reduces
      left ventricular hypertrophy. Fabry disease may be underdiagnosed because of
      nonspecific and multiorgan symptoms. Different screening strategies have been
      carried out in different at-risk populations in order to detect undiagnosed Fabry
      patients. An increasing knowledge about Fabry disease within the medical
      community increases the chances of patients to receive a timely diagnosis and,
      consequently, to access the appropriate therapy.

PMID- 19859979
TI  - Design, development, synthesis, and docking analysis of 2'-substituted triclosan
      analogs as inhibitors for Plasmodium falciparum enoyl-ACP reductase.
AB  - A structure-based approach has been adopted to develop 2'-substituted analogs of
      triclosan. The Cl at position 2' in ring B of triclosan was chemically
      substituted with other functional groups like NH(2), NO(2) and their inhibitory
      potencies against PfENR were determined. The binding energies of the 2'
      substituted analogs of triclosan for enoyl-acyl carrier protein reductase (ENR)
      of Plasmodium falciparum were determined using Autodock. Based on the autodock
      results, we synthesized the potential compounds. The IC(50) and inhibition
      constant (K(i)) of 2' substituted analogs of triclosan were determined against
      purified PfENR. Among them, two compounds, 2-(2'-Amino-4'-chloro-phenoxy)-5
      chloro-phenol (compound 4) and 5-chloro-2-(4'-chloro-2'-nitro-phenoxy)-phenol)
      (compound 5) exhibited good potencies. Compound 4 followed uncompetitive
      inhibition kinetics with crotonoyl CoA and competitive with NADH. It was shown to
      have an IC(50) of 110 nM; inhibition constant was 104 nM with the substrate and
      61 nM with the cofactor. IC(50) of compound 5 was determined to be 229 nM.
      Compounds 4 and 5 showed significant inhibition of the parasite growth in P.
      falciparum culture.

PMID- 19859981
TI  - Calcium regulation of non-kinase and kinase activities of recombinant myosin
      light-chain kinase and its mutants.
AB  - Myosin light-chain kinase (MLCK) comprised of N-terminal actin-binding domain,
      central catalytic domain, and C-terminal myosin-binding domain. It exerted not
      only kinase activity to phosphorylate 20 kDa regulatory light chain of smooth
      muscle but also exerted non-kinase activity on myosin motor and myosin ATPase
      activities (Nakamura et al., Biochem. Biophys. Res. Commun. 2008, 369, 135). The
      previous studies on the multiple MLCK functions were done using MLCK fragments.
      The present study reported the expression of whole MLCK molecules in Escherichia
      coli in a large amount. The construct in which the calmodulin (CaM) binding
      domain for regulating kinase activity was mutated lost the kinase activity.
      However, the mutant exerted non-kinase activity and inhibited both myosin motor
      and ATPase activities. The domain that regulated kinase activity was also shown
      to be involved in the Ca(2+) regulation of non-kinase activity. The deletion
      mutants of actin-binding domain which located at N-terminal 1-41 amino acids
      demonstrated that non-kinase activity was mediated through actin filaments.

PMID- 19859982
TI  - MicroRNA-214 is aberrantly expressed in cervical cancers and inhibits the growth
      of HeLa cells.
AB  - MicroRNAs are a group of endogenously expressed, single-stranded, 18-24 nt RNAs
      that regulate diverse cellular pathways. Although documented evidence indicates
      that some microRNAs can function as oncogenes or tumor-suppressors, the role of
      miR-214 in regulating human cervical cancer cells remains unexplored. We
      determined the expression level of miR-214 and found it is downregulated in
      cervical cancer compared with normal tissue. Overexpression of miR-214 in HeLa
      cells, a human cervical cancer cell line, significantly inhibited cell
      proliferation according to the MTT and colony forming assays. HeLa cells that
      stably overexpress miR-214 downregulate the expression of MEK3 and JNK1 at both
      mRNA and protein levels. Further investigation revealed that miR-214 regulates
      the expression of MEK3 and JNK1 by targeting the 3'UTRs of these genes.
      Collectively, these results suggest that miR-214 negatively regulates HeLa cell
      proliferation by targeting the noncoding regions of MEK3 and JNK1 mRNAs.

PMID- 19859983
TI  - Metal ionophores - an emerging class of anticancer drugs.
AB  - Compounds that bind metals such as copper and zinc have many biological
      activities, including the ability to induce apoptosis in cancer cells. Although
      some of these compounds have been considered to act as chelators of metals,
      decreasing their bioavailability, others increase intracellular metal
      concentrations. We review recent work regarding the recognition of the biological
      effects of metal ionophores with different structures, particularly with regard
      to their actions upon cancer cells focusing on dithiocarbamates, pyrithione, and
      the 8-hydroxyquinoline derivative, clioquinol. We provide a biologically based
      classification of metal-binding compounds that allows an experimental distinction
      between chelators and ionophores that can be readily used by biologists, which
      may lead to further study and classification of metal-binding drugs. Metal
      ionophores may kill cancer cells by a number of mechanisms, including lysosomal
      disruption and proteasome inhibition, and likely others. Because some of these
      compounds have been safely administered to animals and humans, they have the
      potential to become clinically useful anticancer agents.

PMID- 19859980
TI  - Galactose toxicity in animals.
AB  - In most organisms, productive utilization of galactose requires the highly
      conserved Leloir pathway of galactose metabolism. Yet, if this metabolic pathway
      is perturbed due to congenital deficiencies of the three associated enzymes, or
      an overwhelming presence of galactose, this monosaccharide which is abundantly
      present in milk and many non-dairy foodstuffs, will become highly toxic to humans
      and animals. Despite more than four decades of intense research, little is known
      about the molecular mechanisms of galactose toxicity in human patients and animal
      models. In this contemporary review, we take a unique approach to present an
      overview of galactose toxicity resulting from the three known congenital
      disorders of galactose metabolism and from experimental hypergalactosemia.
      Additionally, we update the reader about research progress on animal models, as
      well as advances in clinical management and therapies of these disorders.

PMID- 19859984
TI  - Lnk deletion reinforces the function of bone marrow progenitors in promoting
      neovascularization and astrogliosis following spinal cord injury.
AB  - Lnk is an intracellular adaptor protein reported as a negative regulator of
      proliferation in c-Kit positive, Sca-1 positive, lineage marker-negative (KSL)
      bone marrow cells. The KSL fraction in mouse bone marrow is believed to represent
      a population of hematopoietic and endothelial progenitor cells (EPCs). We report
      here that, in vitro, Lnk(-/-) KSL cells form more EPC colonies than Lnk(+/+) KSL
      cells and show higher expression levels of endothelial marker genes, including
      CD105, CD144, Tie-1, and Tie2, than their wild-type counterparts. In vivo, the
      administration of Lnk(+/+) KSL cells to a mouse spinal cord injury model promoted
      angiogenesis, astrogliosis, axon growth, and functional recovery following
      injury, with Lnk(-/-) KSL being significantly more effective in inducing and
      promoting these regenerative events. At day 3 following injury, large vessels
      could be observed in spinal cords treated with KSL cells, and reactive astrocytes
      were found to have migrated along these large vessels. We could further show that
      the enhancement of astrogliosis appears to be caused in conjunction with the
      acceleration of angiogenesis. These findings suggest that Lnk deletion reinforces
      the commitment of KSL cells to EPCs, promoting subsequent repair of injured
      spinal cord through the acceleration of angiogenesis and astrogliosis.

PMID- 19859985
TI  - Non cell-autonomous reprogramming of adult ocular progenitors: generation of
      pluripotent stem cells without exogenous transcription factors.
AB  - Direct reprogramming of differentiated cells to induced pluripotent stem (iPS)
      cells by ectopic expression of defined transcription factors (TFs) represents a
      significant breakthrough towards the use of stem cells in regenerative medicine
      (Takahashi and Yamanaka Cell 2006;126:663-676). However, the virus-mediated
      expression of exogenous transcription factors could be potentially harmful and,
      therefore, represents a barrier to the clinical use of iPS cells. Several
      approaches, ranging from plasmid-mediated TF expression to introduction of
      recombinant TFs (Yamanaka Cell 2009;137:13-17; Zhou, Wu, Joo et al. Cell Stem
      Cell 2009;4:381-384), have been reported to address the risk associated with
      viral integration. We describe an alternative strategy of reprogramming somatic
      progenitors entirely through the recruitment of endogenous genes without the
      introduction of genetic materials or exogenous factors. To this end, we
      reprogrammed accessible and renewable progenitors from the limbal epithelium of
      adult rat eye by microenvironment-based induction of endogenous iPS cell genes.
      Non cell-autonomous reprogramming generates cells that are pluripotent and
      capable of differentiating into functional neurons, cardiomyocytes, and
      hepatocytes, which may facilitate autologous cell therapy to treat degenerative
      diseases.

PMID- 19859990
TI  - Hepatitis C comorbidities affecting the course and response to therapy.
AB  - Several studies have demonstrated that the outcome of chronic hepatitis C (CHC)
      infection is profoundly influenced by a variety of comorbidities. Many of these
      comorbidities have a significant influence on the response to antiviral therapy.
      These comorbidities negatively affect the course and outcome of liver disease,
      often reducing the chance of achieving a sustained virological response with
      PEGylated interferon and ribavirin treatments. Comorbidities affecting response
      to antiviral therapy reduce compliance and adherence to inadequate doses of
      therapy. The most important comorbidities affecting the course of CHC include
      hepatitis B virus coinfection, metabolic syndrome, and intestinal bacterial
      overgrowth. Comorbidities affecting the course and response to therapy include
      schistosomiasis, iron overload, alcohol abuse, and excessive smoking.
      Comorbidities affecting response to antiviral therapy include depression, anemia,
      cardiovascular disease, and renal failure.

PMID- 19859991
TI  - Achalasia: a review of Western and Iranian experiences.
AB  - Achalasia is a primary motor disorder of the esophagus, in which esophageal
      emptying is impaired. Diagnosis of achalasia is based on clinical findings. The
      diagnosis is confirmed by radiographic, endoscopic, and manometric evaluations.
      Several treatments for achalasia have been introduced. We searched the PubMed
      Database for original articles and meta-analyses about achalasia to summarize the
      current knowledge regarding this disease, with particular focus on different
      procedures that are used for treatment of achalasia. We also report the Iranian
      experience of treatment of this disease, since it could be considered as a model
      for medium-resource countries. Myotomy, particularly laparoscopic myotomy with
      fundoplication, is the most effective treatment for achalasia. Compared to other
      treatments, however, the initial cost of myotomy is usually higher and the
      recovery period is longer. When performing myotomy is not indicated or not
      possible, graded pneumatic dilation with slow rate of balloon inflation seems to
      be an effective and safe initial alternative. Injection of botulinum toxin into
      the lower esophageal sphincter before pneumatic dilation may increase remission
      rates. However, this needs to be confirmed in further studies. Due to lack of
      adequate information regarding the role of expandable stents in the treatment of
      achalasia, insertion of stents does not currently seem to be a recommended
      treatment. In summary, laparoscopic myotomy can be considered as the procedure of
      choice for treatment of achalasia. Graded pneumatic dilation is an effective
      alternative when the performance of myotomy is not possible for any reason.

PMID- 19859992
TI  - Treatment modalities for hypersplenism in liver transplant recipients with
      recurrent hepatitis C.
AB  - Hepatitis C is the most common indication for orthotopic liver transplantation in
      the United States. Unfortunately, hepatitis C recurs universally in the
      transplanted liver and is the major cause of decreased graft and patient
      survival. The combination therapy of interferon and ribavirin has been shown to
      be the most effective therapy for recurrent hepatitis C. However, pre- and post
      transplant hypersplenism often precludes patients from receiving the antiviral
      therapy. Splenectomy and partial splenic embolization are the two invasive
      modalities that can correct the cytopenia associated with hypersplenism. In this
      report we review the two treatment options, their associated outcomes and
      complications.

PMID- 19859993
TI  - Steatosis and insulin resistance in hepatitis C: a way out for the virus?
AB  - The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The
      pathogenesis of steatosis is due to both viral and host factors. Viral steatosis
      is mostly reported in patients with genotype 3a, whereas metabolic steatosis is
      often associated with genotype 1 and metabolic syndrome. Several molecular
      mechanisms responsible for steatosis have been associated with the HCV core
      protein, which is able to induce gene expression and activity of sterol
      regulatory element binding protein 1 (SREBP1) and peroxisome proliferator
      activated receptor gamma (PPARgamma), increasing the transcription of genes
      involved in hepatic fatty acid synthesis. Steatosis has been also implicated in
      viral replication. In infected cells, HCV core protein is targeted to lipid
      droplets which serve as intracellular storage organelles. These studies have
      shown that lipid droplets are essential for virus assembly. Thus, HCV promotes
      steatosis as an efficient mechanism for stable viral replication. Chronic HCV
      infection can also induce insulin resistance. In patients with HCV, insulin
      resistance is more strongly associated with viral load than visceral obesity. HCV
      seems to lead to insulin resistance through interference of intracellular insulin
      signalling by HCV proteins, mainly, the serine phosphorylation of insulin
      receptor-1 (IRS-1) and impairment of the downstream Akt signalling pathway. The
      HCV core protein interferes with in vitro insulin signalling by genotype-specific
      mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in
      genotype 3a and mammalian target of rapamycin (mTOR) in genotype 1 in IRS-1
      downregulation play key roles. Steatosis and insulin resistance have been
      associated with fibrosis progression and a reduced rate of sustained response to
      peginterferon plus ribavirin.

PMID- 19859994
TI  - Do statins reduce hepatitis C RNA titers during routine clinical use?
AB  - AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis
      C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (statins). METHODS: Medical records were reviewed for 6463 patients
      with documented HCV infection at a single center between March 2004 and September
      2006. Patients with confirmed viremia and meeting inclusion criteria were
      assigned to one of three groups: Group A (n = 50), dyslipidemic patients with
      statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group
      B (n = 49), dyslipidemic patients with prior or future statin usage but not at
      the time of HCV RNA PCR determination; and Group C (n = 102), patients without
      statin usage during the study period. The primary analysis explored the effect of
      statin therapy on HCV viremia. Secondary analyses assessed class effect, dose
      response, and effect of other lipid-lowering therapies on HCV viral titers.
      RESULTS: Median HCV RNA titers did not significantly differ among the three
      groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000
      IU/mL). For those subjects with longitudinal assessment of HCV viremia prior to
      and while on statins, there were no significant differences between pre- and post
      HCV viral titers. Additionally, no differences in HCV titers were observed at any
      dose level of the most prescribed statin, simvastatin. However,
      hypertriglyceridemia independently correlated with HCV titers, and niacin
      exposure was associated with significantly lower viral titers (P < 0.05).
      CONCLUSION: There was no apparent effect of statins on HCV viral replication in
      this analysis. Further investigation is warranted to explore the possible
      antiviral properties of triglyceride-lowering agents and their potential role as
      adjuncts to standard HCV therapy.

PMID- 19859995
TI  - Interventional treatment for symptomatic acute-subacute portal and superior
      mesenteric vein thrombosis.
AB  - AIM: To summarize our methods and experience with interventional treatment for
      symptomatic acute-subacute portal vein and superior mesenteric vein thrombosis
      (PV-SMV) thrombosis. METHODS: Forty-six patients (30 males, 16 females, aged 17
      68 years) with symptomatic acute-subacute portal and superior mesenteric vein
      thrombosis were accurately diagnosed with Doppler ultrasound scans, computed
      tomography and magnetic resonance imaging. They were treated with interventional
      therapy, including direct thrombolysis (26 cases through a transjugular
      intrahepatic portosystemic shunt; 6 through percutaneous transhepatic portal vein
      cannulation) and indirect thrombolysis (10 through the femoral artery to superior
      mesenteric artery catheterization; 4 through the radial artery to superior
      mesenteric artery catheterization). RESULTS: The blood reperfusion of PV-SMV was
      achieved completely or partially in 34 patients 3-13 d after thrombolysis. In 11
      patients there was no PV-SMV blood reperfusion but the number of collateral
      vessels increased significantly. Symptoms in these 45 patients were improved
      dramatically without severe operational complications. In 1 patient, the thrombi
      did not respond to the interventional treatment and resulted in intestinal
      necrosis, which required surgical treatment. In 3 patients with interventional
      treatment, thrombi re-formed 1, 3 and 4 mo after treatment. In these 3 patients,
      indirect PV-SMV thrombolysis was performed again and was successful. CONCLUSION:
      Interventional treatment, including direct or indirect PV-SMV thrombolysis, is a
      safe and effective method for patients with symptomatic acute-subacute PV-SMV
      thrombosis.

PMID- 19859996
TI  - Expression of gamma-synuclein in colorectal cancer tissues and its role on
      colorectal cancer cell line HCT116.
AB  - AIM: To investigate the expression pattern of gamma-synuclein in colorectal
      cancer (CRC) tissues, and to study the effects of gamma-synuclein on CRC cell
      line HCT116 biological features in vitro. METHODS: The expression pattern of
      gamma-synuclein was determined in 54 CRC tissues and 30 tumor-matched
      nonneoplastic adjacent tissues (NNAT) 5 cm away from the tumor via real-time
      quantitative reverse transcription PCR (RT-PCR) and immunohistochemistry. The
      relationship between gamma-synuclein protein expression and clinicopathological
      factors of CRC tissues was analyzed. Three small interfering RNA (siRNA)
      targeting gamma-synuclein mRNA plasmids were constructed and transfected into the
      CRC cell line HCT116. The stable cell lines were selected with G-418 for 28 d,
      and the biological features of these cells were examined by cell growth curve,
      soft agar assay, and cell migration and invasion assays in vitro. RESULTS: The
      expression of gamma-synuclein mRNA and protein was much higher in CRC tissue
      samples than in NNAT samples (P = 0.02, P = 0.036). There was a significant
      correlation between the gamma-synuclein protein expression and clinical stage and
      lymph node involvement of CRC (P = 0.02, P = 0.033). In functional analysis we
      found that down-regulation of gamma-synuclein expression in HCT116 cells could
      inhibit the growth, colony formation rate, and migration and invasion ability of
      HCT116 cells. CONCLUSION: Increased expression of gamma-synuclein in CRC tissues
      and the biological effects of reduced gamma-synuclein expression on HCT116 cells
      suggest that gamma-synuclein may play a positive role in the progression of CRC.

PMID- 19859997
TI  - Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude
      mice.
AB  - AIM: To investigate the effects of class I phosphatidylinositol 3-kinase (PI3K)
      inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors
      of SGC7901 human gastric carcinoma cells in nude mice. METHODS: Nude mice were
      randomly divided into model control groups and LY294002 treatment groups. On days
      5, 10 and 15 after treatment, the inhibitory rate of tumor growth, pathological
      changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)
      2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial
      growth factor (VEGF), as well as apoptosis indexes in tumor samples were
      observed. RESULTS: In this study, we showed that treating the tumors with
      LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%,
      after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin &
      eosin staining indicated that the rate of inhibition increased progressively
      (23.51% +/- 3.11%, 43.20% +/- 3.27% and 63.28% +/- 2.10% at 5, 10 and 15 d,
      respectively) along with apoptosis. The expression of MMP-2 was also
      downregulated (from 71.4% +/- 1.6% to 47.9% +/- 0.7%, 31.9% +/- 0.9% and 7.9% +/-
      0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% +/-
      1.5% to 36.9% +/- 0.4%, 23.5% +/- 0.9% and 7.7% +/- 0.6%), the mean MVD (from
      51.2% +/- 3.1% to 41.9% +/- 1.5%, 30.9% +/- 1.7% and 14.9% +/- 0.8%), and the
      expression of VEGF (from 47.2% +/- 3.1% to 25.9% +/- 0.5%, 18.6% +/- 1.2% and
      5.1% +/- 0.9%) by immunohistochemical staining. CONCLUSION: The class I PI3K
      inhibitor LY294002 could inhibit the invasiveness of gastric cancer cells by
      downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

PMID- 19859998
TI  - Liver tumor infiltrating lymphocytes: comparison of hepatocellular and
      cholangiolar carcinoma.
AB  - AIM: To investigate the role of tumor infiltrating lymphocytes (TIL) in primary
      hepatocellular and cholangiolar carcinomas of the liver. METHODS:
      Immunohistochemical analysis was performed including antibodies to CD3, CD4, CD8,
      CD20, CD56 and TIA-1 in formalin-fixed and paraffin-embedded tissue of 35 liver
      resection specimens of hepatocellular or cholangiocellular carcinomas.
      Semiquantitative evaluation was performed with emphasis on the area of the tumor
      itself and of the tumor/liver interface. RESULTS: All hepatocellular carcinomas
      showed infiltration of lymphocytes predominantly around the tumor in the
      tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high
      power fields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF).
      Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of
      CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF)
      and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the
      innate immune system were scarce. There was no significant difference between
      hepatocellular or cholangiolar carcinoma. No correlation with the
      clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral
      CD8+ T cells and peritumoral CD4+ T cells independent of histogenetic origin.
      Different functions of lymphocytes in these regions seem possible.

PMID- 19859999
TI  - UGT1A1 gene polymorphism: impact on toxicity and efficacy of irinotecan-based
      regimens in metastatic colorectal cancer.
AB  - AIM: To investigate the correlation between uridine diphosphate glucuronosyl
      transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side
      effects and parameters of drug efficacy in patients with metastatic colorectal
      cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen.
      METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the
      ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in
      blood samples from 105 patients who had received 1st line irinotecan-based
      chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows:
      wild type genotype (WT) (6/6) 39.0%, heterozygous genotype (6/7) 49.5%, and
      homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar
      between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs
      43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor
      overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in
      patients who carried the (6/6) when compared to the (6/7, 7/7) genotype. No
      significant differences in toxicity were observed: Grade 3 and 4 delayed
      diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7,
      7/7) vs (6/6); 25.1% vs 19.3%, P =0.24] or dose reductions [(6/7, 7/7) vs (6/6);
      21.5% vs 27.2%, P =0.07]. CONCLUSION: This analysis demonstrates the non
      significant influence of the UGT1A1 gene polymorphism on efficacy and rate of
      irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan
      based chemotherapy.

PMID- 19860000
TI  - Patient-reported outcomes in subjects with neuroendocrine tumors of the pancreas.
AB  - AIM: To assess the patient-reported outcomes (PROs) of pancreatic neuroendocrine
      tumor (PNET) patients. METHODS: Fifty-one consecutive patients (21 male, 30
      female, 61.0 +/- 10.3 years) with proven PNETs were studied. An SF-12
      questionnaire capable of exploring the physical (PCS) and mental (MCS) aspects of
      daily life was used. Four questionnaires were also used [12 items General Health
      Questionnaire (GHQ-12) for non-psychotic psychiatric disorders, State Trait
      Anxiety Inventory (STAI) Y-1 and Y-2 for anxiety and BDI-II for depressive
      symptoms] to explore the psychological aspects of the disease. Forty-four sex-
      and age-matched Italian normative subjects were included and evaluated using the
      SF-12, STAI Y-1 and Y-2 questionnaires. RESULTS: Seven patients refused to
      participate to the study; they were clinically similar to the 44 participants who
      agreed to complete the questionnaires. PNET patients had a PCS score (44.7 +/-
      11.0) were not significantly different from the norms (46.1 +/- 9.9, P = 0.610),
      whereas the MCS score was significantly lower in patients (42.4 +/- 13.0) as
      compared to the norms (48.2 +/- 9.8, P = 0.036). GHQ-12 identified 11 patients
      (25.0%) as having non-psychotic psychiatric disorders. The STAI scores were
      similar in the patients and in the normative population. Finally, BDI-II
      identified eight patients (18.2%) with moderate depression and 9 (20.5%) with
      mild depression whereas 27 patients (61.4%) had no depression. CONCLUSION: The
      PNET patients had a good physical but an impaired mental component of their
      quality of life; in addition, mild or moderate depressive symptoms are present in
      about 40% of PNET patients.

PMID- 19860001
TI  - High circulating N-terminal pro-brain natriuretic peptide and tumor necrosis
      factor-alpha in mixed cryoglobulinemia.
AB  - AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide
      (NTproBNP) and tumor necrosis factor alpha (TNF-alpha) in a large series of
      patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV).
      METHODS: Serum NTproBNP and TNF-alpha levels were assayed in 50 patients with
      MC+HCV, and in 50 sex- and age-matched controls. RESULTS: Cryoglobulinemic
      patients showed significantly higher mean NTproBNP and TNF-alpha levels than
      controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a
      value higher than 125 pg/mL (the single cut-off point for outpatients under 75
      years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (c2, P < 0.01).
      With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in
      patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP
      (c2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in
      patients aged 50-75 years; such as the patients of our study), 6% of MC+HCV and 0
      controls had high NTproBNP (c2, P = 0.08). CONCLUSION: The study demonstrates
      high levels of circulating NTproBNP and TNF-alpha in MC+HCV patients. The
      increase of NTproBNP may indicate the presence of a subclinical cardiac
      dysfunction.

PMID- 19860002
TI  - Hepatitis C virus genotype 3a infection and hepatocellular carcinoma: Pakistan
      experience.
AB  - AIM: To assess the association between chronic hepatitis C virus (HCV) infection
      and hepatocellular carcinoma (HCC) in Pakistan, and the genotype distribution
      among these HCC patients. METHODS: One hundred and sixty-one subjects with HCC
      were included in this study. Liver biopsy was performed on 145 of the patients;
      sixteen were excluded because they failed to fulfill the inclusion criteria.
      Qualitative polymerase chain reaction (PCR) was performed for hepatitis B virus
      and HCV. Samples positive for HCV RNA were genotyped using genotype-specific PCR
      and confirmed by HCV 5' noncoding region sequencing analysis. RESULTS: Chronic
      HCV infection was identified a major risk factor (63.44% of tested HCC patients)
      for the development of HCC. The time from HCV infection to appearance of cancer
      was 10-50 years. In the HCC patient population, broader distributions of
      genotypes were present with genotype 3a as the predominant genotype. Using the
      type-specific genotyping method, we found HCV genotype 3a in 40.96%, 3b in
      15.66%, 1a in 9.63%, and 1b in 2.40% of HCC tissue samples. About 28% of cases
      were found with mixed genotypes. Two cases were unable to be genotyped because of
      low viral load. Sixty-six percent of treated patients with cirrhosis had an end
      of treatment response, but unfortunately they relapsed quickly when the treatment
      was discontinued, and HCC developed during a median 3.8 years. CONCLUSION: There
      was a strong association between chronic HCV infection and HCC in Pakistan, and
      between HCV genotype 3a and HCC.

PMID- 19860003
TI  - Gastric leptomeningeal carcinomatosis: multi-center retrospective analysis of 54
      cases.
AB  - AIM: To identify the clinical features and outcomes of infrequently reported
      leptomeningeal carcinomatosis (LMC) of gastric cancer. METHODS: We analyzed 54
      cases of cytologically confirmed gastric LMC at four institutions from 1994 to
      2007. RESULTS: The male-to-female ratio was 32:22, and the patients ranged in age
      from 28 to 78 years (median, 48.5 years). The majority of patients had advanced
      disease at initial diagnosis of gastric cancer. The clinical or pathologic tumor,
      node and metastasis stage of the primary gastric cancer was IV in 38 patients
      (70%). The median interval from diagnosis of the primary malignancy to the
      diagnosis of LMC was 6.3 mo, ranging between 0 and 73.1 mo. Of the initial
      endoscopic findings for the 45 available patients, 23 (51%) of the patients were
      Bormann type III and 15 (33%) patients were Bormann type IV. Pathologically, 94%
      of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell
      component was also observed in 40% of patients. Headache (85%) and
      nausea/vomiting (58%) were the most common presenting symptoms of LMC. A
      gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients.
      Leptomeningeal enhancement was noted in 45 cases (82%). Intrathecal (IT)
      chemotherapy was administered to 36 patients-primarily methotrexate alone (61%),
      but also in combination with hydrocortisone/+/- Ara-C (39%). The median number of
      IT treatments was 7 (range, 1-18). Concomitant radiotherapy was administered to
      18 patients, and concomitant chemotherapy to seven patients. Seventeen patients
      (46%) achieved cytological negative conversion. Median overall survival duration
      from the diagnosis of LMC was 6.7 wk (95% CI: 4.3-9.1 wk). In the univariate
      analysis of survival duration, hemoglobin, IT chemotherapy, and cytological
      negative conversion showed superior survival duration (P = 0.038, P = 0.010, and
      P = 0.002, respectively). However, in our multivariate analysis, only cytological
      negative conversion was predictive of relatively longer survival duration (3.6,
      6.7 and 14.6 wk, P = 0.030, RR: 0.415, 95% CI: 0.188-0.918). CONCLUSION: Although
      these patients had a fatal clinical course, cytologic negative conversion by IT
      chemotherapy may improve survival.

PMID- 19860005
TI  - Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug
      induced ulcer in Japan.
AB  - AIM: To investigate the efficacy and safety of rabeprazole under continuous non
      steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer
      in Japan. METHODS: Subjects comprised patients undergoing NSAID treatment in whom
      upper gastrointestinal endoscopy revealed an ulcerous lesion (open ulcer) with
      diameter > or = 3 mm, who required continuous NSAID treatment. Endoscopies were
      performed at the start of treatment, during the treatment period, and at the
      conclusion (or discontinuation) of treatment. Findings were evaluated as size
      (maximum diameter) and stage based on the Sakita-Miwa classification. An ulcer
      was regarded as cured when the "white coating" was seen to have disappeared under
      endoscopy. As criteria for evaluating safety, all medically untoward symptoms and
      signs (adverse events, laboratory abnormalities, accidental symptoms, etc.)
      occurring after the start of rabeprazole treatment were handled as adverse
      events. RESULTS: Endoscopic cure rate in 38 patients in the efficacy analysis
      (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had
      gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a
      cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64
      patients in the safety analysis (interstitial pneumonia, low white blood cell
      count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7%
      (3/64). CONCLUSION: The treatment efficacy of rabeprazole for NSAID-induced ulcer
      under continuous NSAID administration was confirmed.

PMID- 19860004
TI  - Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific
      type V phosphodiesterase inhibitor.
AB  - AIM: To investigate the gastroprotective effect of vardenafil against
      indomethacin-induced gastric damage. METHODS: Forty-eight female Wistar albino
      rats were randomly divided into 6 groups. Group 1 received saline only. Group 2
      (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with
      different doses of famotidine. Group 5 and 6 were pretreated with different doses
      of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after
      pretreatment. The animals were sacrificed 6 h later and their stomachs were
      opened. Gastric lesions were counted and measured. The stomach of each animal was
      divided in two parts for histopathological examinations and nitric oxide (NO) and
      malondialdehyde (MDA) assays, respectively. RESULTS: There were no gastric
      mucosal lesion in the saline group but all rats in the indomethacin group had
      gastric mucosal ulcerations (ulcer count; 6.25 +/- 3.49, and mean ulcer area;
      21.00 +/- 12.35). Ulcer counts were diminished with famotidine 5 mg/kg (4.12 +/-
      2.47, P > 0.05), 20 mg/kg (2.37 +/- 4.43, P < 0.05), vardenafil 2 mg/kg (4.37 +/-
      3.06), and vardenafil 10 mg/kg (1.25 +/- 1.38, P < 0.05) compared to the
      indomethacin group. Gastric mucosal lesion areas were diminished with famotidine
      5 mg/kg (8.62 +/- 2.97, P < 0.001) , famotidine 20 mg/kg (0.94 +/- 2.06, P <
      0.001), vardenafil 2 mg/kg (6.62 +/- 5.87, P < 0.001), and vardenafil 10 mg/kg
      (0.75 +/- 0.88, P < 0.001) compared to the indomethacin group. MDA levels were
      significantly higher in indomethacin group (28.48 +/- 14.51), compared to the
      famotidine 5 mg/kg (6,21 +/- 1.88, P < 0.05), famotidine 20 mg/kg (5.88 +/- 1.60.
      P < 0.05), vardenafil 2 mg/kg (15.87 +/- 3.93, P < 0.05), and vardenafil 10 mg/kg
      (10.97 +/- 4.50, P < 0.05). NO concentration in gastric tissues of the famotidine
      groups were significantly increased (P < 0.05), but the NO increases in the
      vardenafil groups were not statistically significant. Histopathology revealed
      diminished gastric damage for pretreatment groups compared to the indomethacin
      group (P < 0.05). CONCLUSION: Vardenafil affords a significant dose-dependent
      protection against indomethacin induced gastric mucosal lesions in rats.

PMID- 19860006
TI  - Unexplained liver laceration after metastasis radiofrequency ablation.
AB  - Many studies have established the role of radiofrequency (RF) ablation as a
      minimally invasive treatment for liver metastases. Although relatively safe,
      several complications have been reported with the increased use of RF ablation.
      We describe here a case of unexplained liver laceration after a RF procedure. A
      woman who presented a solitary metachronous liver metastasis underwent RF
      ablation treatment for this lesion. Six hours later the patient displayed fatigue
      and pallor. Emergency blood tests showed a haemoglobin level of < 7 g/dL and
      markedly elevated transaminase levels. A computed tomography examination revealed
      two areas of liver laceration with haematoma, one of them following the path of
      the needle and the other leading away from the first. Following a blood
      transfusion, the patient was haemodynamically stable and completely recovered 24
      h later. The patient remained in bed for 1 wk. No surgical intervention was
      required, and she was discharged 1 wk later.

PMID- 19860007
TI  - Gastric choriocarcinoma admixed with an alpha-fetoprotein-producing
      adenocarcinoma and separated adenocarcinoma.
AB  - We report a case of gastric choriocarcinoma admixed with an alpha-fetoprotein
      (AFP)-producing adenocarcinoma. A 70-year-old man was hospitalized for gastric
      cancer that was detected during screening by esophagogastroduodenoscopy (EGD).
      Initial laboratory data showed the increased serum level of AFP and EGD revealed
      a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum. The
      patient underwent radical subtotal gastrectomy with D2 lymph node dissection and
      Billroth II gastrojejunostomy. Histopathological evaluation confirmed double
      primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing
      adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human
      chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant
      chemotherapy were initiated. No recurrence or distant metastasis was observed at
      4 years postoperatively.

PMID- 19860008
TI  - A case of intussuscepted Meckel's diverticulum.
AB  - We report colonoscopic features of an intussuscepted Meckel's diverticulum,
      presenting with hematochezia. A 35-year-old woman presented to the emergency room
      with acute onset, transient, sharp, severe epigastric pain that began 6 h
      earlier. Colonoscopy revealed a reddish, soft, fist-sized polypoid lesion in the
      terminal ileum. The lesion was misinterpreted as a hematoma by an inexperienced
      endoscopist. The patient began to complain of intermittent, severe periumbilical
      pain following the colonoscopic examination. Subsequent computed tomography
      showed an enteric intussusception. An exploratory laparotomy revealed an
      intussuscepted Meckel's diverticulum, with transmural infarction. Colonoscopy was
      of little use in assessing the intussusception. However, colonoscopic examination
      may be performed initially, especially in an intussuscepted Meckel's diverticulum
      presenting with hematochezia. Endoscopists should note the endoscopic features of
      an intussuscepted Meckel's diverticulum.

PMID- 19860009
TI  - Liver transplantation for polycystic liver with massive hepatomegaly: a case
      report.
AB  - A previous study has shown that liver or combined liver-kidney transplantation
      can be a valuable surgical technique for the treatment of polycystic liver
      disease. Herein, we present the case of a 35-year-old woman with polycystic liver
      disease, who underwent orthotopic liver transplantation (OLT) on November 11,
      2008. The whole-size graft was taken from a deceased donor (a 51-year-old man who
      died of a heart attack). Resection in a patient with massive hepatomegaly is very
      difficult. Thus, after intercepting the portal hepatic vein, left hepatectomy was
      performed, then the vena cava was intercepted, the second and third porta hepatic
      isolated, and finally, right hepatectomy was performed. OLT was performed
      successfully. The recipient did well after transplantation. This case suggested
      that OLT is an effective therapeutic option for polycystic liver disease and left
      hepatectomy can be performed first during OLT if the liver is over enlarged.

PMID- 19860010
TI  - Association of hepatitis C virus infection and diabetes.
AB  - Epidemiologic studies have suggested a relation between hepatitis C virus (HCV)
      infection and diabetes mellitus. HCV infection is emerging as a metabolic
      disease, and diabetes mellitus as a risk factor for HCV infection. However, some
      data on the prevalence of antibodies to HCV in patients with diabetes are
      conflicting. These seroprevalence data should be interpreted with caution. Some
      potential bias may occur in those clinic-based studies that target a specific
      disease group. In this letter we explain some reasons for these conflicting
      studies.

PMID- 19860011
TI  - VentrAssist left ventricular assist systems long-term in vitro reliability.
AB  - Left ventricular assist systems (LVADs) are typically tested for long-term
      reliability by using a simulated human cardiovascular system. In this study,
      13VentrAssist (Ventracor Ltd, Chatswood, NSW, Australia)systems are tested in
      mock loops with the aim of demonstrating in vitro continuous operational
      reliability of the pump subsystem greater than 80% (60%confidence) over 1 year.
      As of July 9, 2007, the total time on test of all 13 mock loop pumps is 29.36
      years. In vitro reliability of the VentrAssist LVAD blood pump is 96.7%(60%
      confidence) at 1 year. No failures have been seen over 4.5 years of test, and
      testing is ongoing.

PMID- 19860012
TI  - In-hospital cardiopulmonary resuscitation.

PMID- 19860014
TI  - "Everyone has a right to, like, check their box:" findings on a measure of gender
      identity from a cognitive testing study with adolescents.
AB  - Efforts to monitor the health of transgender youth, a small but high-risk
      population, are hindered by a lack of knowledge about how to accurately measure
      gender identity. Adolescents (n = 30) participated in semistructured qualitative
      interviews after completing a close-ended transgender-inclusive measure of
      gender. Interviews explored item comprehension and respondent burden.
      Participants, who were diverse in age (range = 15-21), gender identity, sexual
      orientation, and race-ethnicity, were accurately classified as male, female, or
      transgender. All youth understood transgender as a difference between the
      physical body and a person's internal sense of self. Nontransgender youth
      frequently used an example (a woman in a man's body) in their explanations and
      were largely supportive of the transgender options. Most transgender youth found
      a response option that they felt was appropriate. Transgender response options
      were added to a gender measure without impacting the accuracy of nontransgender
      responses or burdening the nontransgender adolescents in our sample. A modified
      measure (Gender: male; female; transgender, male-to-female; transgender, female
      to-male; transgender, do not identify as exclusively male or female) is
      recommended for testing in samples that vary by age, race-ethnicity,
      socioeconomic status, language, and geography. Additional suggestions for
      research in this area are provided.

PMID- 19860013
TI  - The CBL-CIPK Ca(2+)-decoding signaling  network: function and perspectives.
AB  - Calcium serves as a versatile messenger in many adaptation and developmental
      processes in plants. Cellular calcium signals are detected and transmitted by
      calcium-binding proteins functioning as sensor molecules. The family of
      calcineurin B-like (CBL) proteins represents a unique group of calcium sensors
      and contributes to the decoding of calcium transients by interacting with and
      regulating the family of CBL-interacting protein kinases (CIPKs). In higher
      plants, CBL proteins and CIPKs form a complex signaling network that allows for
      flexible but specific signal-response coupling during environmental adaptation
      reactions. This review presents novel findings concerning the evolution of this
      signaling network and key insights into the physiological function of CBL-CIPK
      complexes. These aspects will be presented and discussed in the context of
      emerging functional principles governing efficient and specific information
      processing in this signaling system.

PMID- 19860015
TI  - Inclusion of lesbian, gay, bisexual and transgender people in tobacco use-related
      surveillance and epidemiological research.
AB  - Researchers and public health advocates have long recognized the importance of
      demographic characteristics such as sex, race, ethnicity, age, and socioeconomic
      status in their efforts to understand and control the use of tobacco among
      population groups. Targeting prevention and cessation efforts based upon such
      characteristics has consistently been demonstrated to be both efficient and
      effective. In recent years, attention has modestly turned to how two additional
      demographic variables, sexual orientation and gender identity, can add to our
      understanding of how to reduce tobacco use. Research of tobacco industry papers
      has clearly documented targeted media campaigns to encourage smoking among
      lesbians and gays in the marketplace. The tobacco industry has long understood
      the role that sexual orientation can play in the uptake of smoking and the
      targeted marketing of brands. Those concerned with tobacco use prevention and
      cessation research have consequently responded to address tobacco use by lesbians
      and gays, and bisexuals and transgender people as well, but even more can be
      done. This article reviews what is known about smoking in lesbian, gay, bisexual,
      and transgender populations and then reviews recommendations from four panels
      created to examine this topic. In conclusion, we recommend that sexual
      orientation and gender identity be considered for inclusion as variables in all
      major research and epidemiological studies of tobacco use. Just as such studies,
      without hesitation, measure sex, race, ethnicity, age, and socioeconomic status,
      they need to also include questions assessing sexual orientation and gender
      identity. Although these new variables need not be the primary focus of these
      studies, at a minimum, considering their use as controlling variables should be
      explored. Lesbian, gay, bisexual, and transgender people can benefit from being
      openly included in the work researchers conduct to inform the design of tobacco
      control programs and policies.

PMID- 19860016
TI  - Reply to Jongschaap et al.: The water footprint of Jatropha curcas under poor
      growing conditions.

PMID- 19860017
TI  - [Changes in the composition of populations of Phytophthora infestans (Mont.) de
      Bary in Russia in the 1990s based on the results of mitochondrial DNA analysis].
AB  - Changes in the composition of the populations of Phytophthora infestans, the
      agent of late blight of potato and open-ground tomato, occurred in Russia in the
      early 1990s. These changes were detected via analysis of mitochondrial DNA
      (mtDNA) and other characteristics in 219 isolates of P. infestans. It was
      demonstrated that these changes were similar to those that occurred in European
      populations of the fungus in the early 1980s, when "old" genotypes were rapidly
      displaced by "new" ones. Possible causes of this phenomenon, which is related to
      the characteristics of the parasite's biology, and of host specialization are
      discussed.

PMID- 19860019
TI  - Global Action Plan for the Prevention and Control of Pneumonia in children aged
      under 5 years.

PMID- 19860018
TI  - Progress towards eradicating poliomyelitis in Nigeria, January 2008-  July 2009.

PMID- 19860020
TI  - The intellectual legacy of Mary Neth's work on farm women and rural communities.
AB  - Mary Neth's 1995 book, "Preserving the Family Farm: Women, Community, and the
      Foundations of Agribusiness in the Midwest, 1900-1940," made a major contribution
      to the analysis of the connections between gender and the political economy that
      shaped farm women's lives and fueled farmers' resistance to the transformation of
      rural life wrought by agribusiness. Focusing on the processes of negotiation
      between women and men in farming families and rural communities, Neth illuminated
      the relationship between women's work and their power. Tracing the dense networks
      that connected farm families, she also showed how cooperation in work generated
      and sustained radical farm movements.

PMID- 19860021
TI  - Global programme to eliminate lymphatic filariasis.

PMID- 19860022
TI  - Telling stories: keeping secrets.
AB  - This article addresses the reticence of some farm women to share their
      experiences with historians and how that desire to keep secrets collides with the
      desire by scholars to tell the stories of these women. It argues that scholars
      must continue to struggle with the issue of which stories to tell publicly and
      which to keep private. The author discusses her own experience telling stories
      about rural women in the 1970s and the need to give voice to the heritage of
      rural women, especially of groups that have feared revealing their experiences.
      She offers examples of historians of rural women who have successfully worked
      with formerly silenced populations and urges historians to continue to tell
      stories about these lives, to reevaluate what has been already learned, to ask
      new questions, and to discuss which secrets need to be shared.

PMID- 19860023
TI  - "Not to intrude": a Danish perspective on gender and class in nineteenth-century
      dairying.
AB  - This study follows the thread of gender divisions in dairying in Denmark and the
      American Midwest in the late nineteenth and early twentieth centuries. Gender
      organization of dairying shifted at this time in diverse European and North
      American contexts. As agriculture mechanized and production scale increased,
      access to advanced education and international markets became critical. Women,
      who had been in the forefront of the development of dairying, ceded their
      leadership to men as these changes occurred. While some scholars see this shift
      as a strategic loss for women, this study finds that variables of class, marital
      status, rural demographics, and alternative occupations mediated the rural
      women's experience of change. Not all women experienced the change as a loss. The
      question of which women were invested in dairying is critical to understanding
      the course of change. Increasingly, middle-class farm women were turning away
      from the hard work of dairying and investing themselves in new ways in the upward
      mobility of their family farms. Rural life shaped distinct gender patterns in
      European and American history, and the rural experience shaped the larger
      trajectory of women's economic and political evolution, even though few rural
      women were involved in the organized women's movement.

PMID- 19860024
TI  - Global Advisory Committee on Vaccine Safety, report of meeting held 17-18 June
      2009.

PMID- 19860025
TI  - Highlights from the 49th ICAAC.

PMID- 19860026
TI  - HIV drug patents in the spotlight.

PMID- 19860027
TI  - Universal access not a dream.

PMID- 19860028
TI  - Not our problem.

PMID- 19860029
TI  - "Hop to the top with the Iowa Chop": the Iowa Porkettes and cultivating agrarian
      feminisms in the Midwest, 1964-1992.
AB  - Over the course of twenty-eight years, between 1964 and 1991, members of the Iowa
      Porkettes, the women's auxiliary to the Iowa Pork Producer's Association (IPPA),
      promoted pork products in order to assert their roles as agricultural producers.
      For the members of the Porkettes, technological change and the growth of
      agribusiness provided new opportunities to challenge patriarchal hierarchies in
      agricultural organizations. Over time, as the overall number of hog farmers
      declined and the agricultural marketplace increasingly demanded professional
      expertise, the Porkettes transformed a women's auxiliary into a female-led
      commodity organization. Initially, members participated in appropriately
      "feminine" activities including Pork Queen contests, lard-baking contests,
      consultations with high school home economics instructors, and the distribution
      of promotional materials. By the late 1970s, however, members began to employ a
      new rhetoric shaped by their labor on the farm to claim an important stake in the
      production and marketing of commodities. They took responsibility for large-scale
      advertising campaigns, managed a growing budget, and became leaders within the
      IPPA. Their experiences offer insight into broader developments of second wave
      agrarian feminisms that enabled farm women's organizations to renegotiate
      gendered divisions of labor, claim new public spaces for women, and demand
      greater recognition from male agricultural leaders.

PMID- 19860030
TI  - "So long as I can read": farm women's reading experiences in Depression-era South
      Dakota.
AB  - During the Great Depression, with conditions grim, entertainment scarce, and
      educational opportunities limited, many South Dakota farm women relied on reading
      to fill emotional, social, and informational needs. To read to any degree, these
      rural women had to overcome multiple obstacles. Extensive reading (whether books,
      farm journals, or newspapers) was limited to those who had access to publications
      and could make time to read. The South Dakota Free Library Commission was
      valuable in circulating reading materials to the state's rural population. In the
      1930s the commission collaborated with the USDA's Extension Service in a popular
      reading project geared toward South Dakota farm women. This "Reading in the Home"
      program greatly increased reading opportunities and motivations. Of particular
      interest to rural women were tales of pioneer life featuring strong protagonists.
      Through these stories, farm women found validation and encouragement to
      persevere. Reading also broadened horizons and challenged assumptions. For the
      depression-era farm woman, reading books and other materials provided recreation,
      instruction, and inspiration in a discouraging time.

PMID- 19860031
TI  - Self-regulation of recombinant DNA technology in Japan in the 1970s.
AB  - Recombinant DNA technology was developed in the United States in the early 1970s.
      Leading scientists held an international Asilomar Conference in 1975 to examine
      the self regulation of recombinant DNA technology, followed by the U.S. National
      Institutes of Health drafting the Recombinant DNA Research Guidelines in 1976.
      The result of this conference significantly affected many nations, including
      Japan. However, there have been few historical studies on the self-regulation of
      recombinant technologies conducted by scientists and government officials in
      Japan. The purpose of this paper is to analyze how the Science Council of Japan,
      the Ministry of Education, Science adn Culture, and the Science and Technology
      Agency developed self-regulation policies for recombinant DNA technology in Japan
      in the 1970s. Groups of molecular biologist and geneticists played a key role in
      establishing guidelines in cooperation with government officials. Our findings
      suggest that self-regulation policies on recombinant DNA technology have
      influenced safety management for the life sciences and establishment of
      institutions for review in Japan.

PMID- 19860032
TI  - Brainhood, anthropological figure of modernity.
AB  - If personhood is the quality or condition of being an individual person,
      "brainhood" could name the quality or condition of being a brain. This
      ontological quality would define the "cerebral subject" that has, at least in
      industrialized and highly medicalized societies, gained numerous social
      inscriptions since the mid-20th century. This article explores the historical
      development of brainhood. It suggests that the brain is necessarily the location
      of the "modern self," and that, consequently, the cerebral subject is the
      anthropological figure inherent to modernity (at least insofar as modernity gives
      supreme value to the individual as autonomous agent of choice and initiative). It
      further argues that the ideology of brainhood impelled neuroscientific
      investigation much more than it resulted from it, and sketches how an expanding
      constellation of neurocultural discourses and practices embodies and sustains
      that ideology.

PMID- 19860033
TI  - Abdominal wall reconstruction using biological tissue grafts.
AB  - Synthetic mesh products have been used to repair abdominal wall defects (eg,
      hernias) for many years. Biological mesh products are now available as an option
      when synthetic mesh products are not appropriate. To correctly prepare biological
      tissue grafts for use in the OR, perioperative nurses must understand the types
      of grafts available. Biological tissue grafts may be harvested from human,
      porcine, bovine, or equine hosts and from skin, pericardium, or small intestine
      submucosa.

PMID- 19860034
TI  - Bowel prep for ambulatory endoscopy.

PMID- 19860035
TI  - Your brain: use it or lose it.

PMID- 19860036
TI  - Care plans: Deja vu all over again.

PMID- 19860037
TI  - Your patient with melanoma: staging, prognosis, and treatment.
AB  - Melanoma, a cancer of melanocytes, pigment-producing cells in the skin, is the
      most serious form of skin cancer. Its incidence is increasing rapidly and
      reaching epidemic proportions. When detected early, it is considered curable, but
      when detected at later stages it is arguably one of the most lethal malignancies
      and is the cause of more years of lost life than any other cancer except
      leukemia. Because most cutaneous melanomas are visible, however, melanoma in
      general is a cancer highly amenable to early detection. Surgery is standard
      treatment for localized melanoma. There is no standard therapy for advanced-stage
      melanoma. Metastatic melanoma disseminates widely and it frequently involves
      sites that are not commonly affected in other cancers, such as the
      gastrointestinal tract and skin. The median survival time for patients with
      metastatic melanoma is less than 1 year. Despite these grim statistics, long-term
      survival occurs occasionally. This article will review diagnosis, staging, and
      treatment for malignant melanoma and will discuss the nursing role in the care of
      patients with melanoma.

PMID- 19860038
TI  - Melanoma: an under-recognized cancer threat.

PMID- 19860039
TI  - Oral mucositis in radiation/chemotherapy: treatment similarities.

PMID- 19860040
TI  - Fatigue in long-term cancer survivors.

PMID- 19860041
TI  - Living to the end: Merging holistic and evidence-based strategies to meet the
      needs of people living with advanced cancer.
AB  - With advances in the treatment and long-term management of cancer, the number of
      people living with metastatic and advanced cancers has continued to grow. Yet
      their issues and concerns, and those of their family caregivers, are often
      neglected. Despite the paucity of high levels of evidence for best-practice care
      of this distinct survivor population, we can and must start now to consistently
      address their needs, changing or adapting practice as new evidence becomes
      available. This article provides a review of the literature focusing primarily on
      the needs of patients/caregivers and highlights holistic nursing activities and
      programmatic services that are suggested by available data.

PMID- 19860042
TI  - Transitioning to cancer survivorship: plans of care.
AB  - Survivorship care plans have received increasing attention since the 2006 release
      of the Institute of Medicine report, From Cancer Patient to Cancer Survivor: Lost
      in Transition. The report strongly recommends that at completion of cancer
      treatment, clinicians provide patients with a summary of treatment delivered and
      a detailed plan of ongoing care, including follow-up schedules for visits and
      testing, as well as recommendations for early detection and management of
      treatment-related effects and other health problems. Templates have been
      developed by various groups to support the effort involved in complying with this
      recommendation. Barriers exist, such as difficulties in accessing information,
      preparation time involved for busy clinicians, lack of third-party reimbursement,
      and absence of clear guidelines for follow-up care after cancer treatment. The
      absence of research related to care plans and patient outcomes also calls their
      necessity into question. Yet, there is a growing acceptance among oncology
      physicians and nurses that having a plan of care is an essential component of
      quality survivorship care.

PMID- 19860043
TI  - Information for patients. HER2: what you need to know.

PMID- 19860044
TI  - Nursing leadership in survivor care.

PMID- 19860045
TI  - Living life to the fullest: an essential goal.

PMID- 19860046
TI  - New mTOR inhibitor for renal cell cancer.

PMID- 19860047
TI  - Time to deliver for aged care in Budget 2010.

PMID- 19860048
TI  - Inadequate response in aged care.

PMID- 19860049
TI  - Indigenous health: a time for action.

PMID- 19860050
TI  - Info-jection: dispelling myths and overcoming fears.

PMID- 19860051
TI  - Working for change.

PMID- 19860052
TI  - Justice as a basic human need.

PMID- 19860054
TI  - Engagement skills.

PMID- 19860053
TI  - Strategies to reduce medication errors in older adults.

PMID- 19860055
TI  - Welcome to the jungle.

PMID- 19860056
TI  - Desperately looking for work.

PMID- 19860057
TI  - Backwards studying: study smarter, not harder.

PMID- 19860058
TI  - Easing apprehension: coping strategies for student nurses' anxiety.

PMID- 19860060
TI  - Nurses at heart of drive to speed up cancer diagnosis.

PMID- 19860059
TI  - Are you ready? Gearing up for clinical.

PMID- 19860061
TI  - Trespassers on medical ground?

PMID- 19860062
TI  - Nurses should consider training in CBT to support COPD patients.

PMID- 19860063
TI  - Exploring the outcomes and implications of the latest national COPD audit.
AB  - Publication of the clinical strategy for COPD is expected at the end of the year
      and it is anticipated that this will provide a structure to improve management of
      the condition. The latest national COPD audit has shown that although services
      have improved since the last audit in 2003, there are key areas in COPD
      management that need to be improved. This article analyses the results of this
      audit and the implications for practice.

PMID- 19860064
TI  - Using cognitive behavioural therapy to address the psychological needs of
      patients with COPD.
AB  - This article describes the psychological impact of chronic obstructive pulmonary
      disease and outlines how cognitive behavioural therapy can be used to manage
      problems. It presents the results of research using CBT with this patientgroup.

PMID- 19860065
TI  - Smoking cessation 1: best practice and treatment and support options for
      patients.
AB  - This first in a two-part unit on smoking cessation examines why smoking is so
      addictive and how healthcare professionals can support patients to quit. It
      outlines treatment options such as pharmacotherapy and behavioural support.

PMID- 19860066
TI  - Reducing COPD admissions with a specialist chronic disease management team.
AB  - This article describes the implementation of a specialist community team working
      with acute care services to manage patients with COPD. It resulted in a sustained
      reduction in hospital admissions over one year.

PMID- 19860067
TI  - Care planning in long term conditions: nurse-led care plans for people with
      diabetes.
AB  - This is the second article in a three-part series on personalised care planning
      for patients with long term conditions (part 1 appeared as an 'In depth' article
      last week). It describes how Burn Brae Medical Group is piloting care planning
      for patients with diabetes as part of the Year of Care programme. The practice
      first trialled care planning for this group in 2004.

PMID- 19860069
TI  - The debate around public service cuts lacks logic.

PMID- 19860068
TI  - Osteoporosis and fragility fractures: identifying those at risk and raising
      public awareness.
AB  - This article outlines key points for nurses in delivering optimal osteoporosis
      care. It describes the epidemiology of the condition, risk factors, risk
      assessment, screening and treatment. It also discusses the importance of raising
      awareness and future developments in treating this increasingly common condition.

PMID- 19860070
TI  - On why nurses must get on top of NHS finance.

PMID- 19860072
TI  - Factors related to admission of psychiatric patients to medical wards from the
      general hospital emergency department: a 3-year study of urgent psychiatric
      consultations.
AB  - OBJECTIVE: Emergency Rooms (ER) of Emergency Departments (ED) in General
      Hospitals (GH) have a role in providing for psychiatric evaluation. The aims of
      the present study were to examine the decision-making process of consultation
      psychiatry at the GH-ER and to analyze the differences between psychiatric
      patients admitted to a medical ward with those admitted to the psychiatry unit
      and those who are discharged from the ER. METHOD: Over a period of 3 years,
      psychiatric consultations requested by ER of ED physicians to the GH Psychiatric
      service were recorded by using a form to describe epidemiological and clinical
      data on the consultation process. RESULTS: Of 1,962 psychiatric consultations,
      most regarded subjects who had had previous psychiatric contacts (76.2%) and at
      least one psychiatric admission (53.6%), and were currently cared for by the
      Mental Health Services (51.1%). Neurotic/stress-related syndromes (27.98%),
      schizophrenia (27.67%), and personality disorders (21.81%) were the most frequent
      ICD-10 diagnoses. The psychiatrist's disposal was to discharge the patient in
      49.9% cases, to admit him/her to medical wards of the GH (MGH; 26.9%) or to the
      acute inpatient psychiatric ward (AIP; 23.1%). MGH group statistically differed
      from AIP group for being female (p < 0.01), older (p < 0.01), more likely having
      an ICD-10 diagnosis of neurosis/stress-related syndromes (p < 0.01) or organic
      mental disorder (p < 0.01), and less likely having a diagnosis of schizophrenia
      (p < 0.01), being in charge of the Mental Health Services (p < 0.01), and having
      had previous psychiatric admissions (p < 0.01). These results were confirmed by
      logistic regression analysis. CONCLUSIONS: The study shows that the medical wards
      of the General Hospital are a significant entry-point for providing psychiatric
      care of patients with ICD-10 neurotic and stress-related syndromes, even if
      without specific medical problems.

PMID- 19860073
TI  - The abuse of prescription medications: borderline personality patients in
      psychiatric versus non-psychiatric settings.
AB  - OBJECTIVE: In this study, the prevalence of prescription substance abuse among
      those with borderline personality symptomatology was examined in a large cohort
      of respondents who participated in one of 13 prior research projects. METHOD: The
      entire cohort (N = 1039) was divided into 3 subsamples: a psychiatric sample (n =
      440), a predominantly primary care sample (n = 599), and an internal medicine
      sample (n = 332; i.e., a well-defined subset of the predominantly primary care
      sample that consisted of only internal medicine outpatients seen at one
      location). The borderline personality scale of the Personality Diagnostic
      Questionnaire (PDQ), either the revised (PDQ-R) or fourth (PDQ-4) version, was
      used to diagnose all participants either with or without borderline personality.
      One item from the Self-Harm Inventory, "Have you ever intentionally, or on
      purpose, abused prescription medication?," was then used in the subsequent
      analyses. RESULTS: Among the psychiatric, predominantly primary care, and
      internal medicine subsamples, the prevalence rates of prescription medication
      abuse in those diagnosed with borderline personality according to the PDQ were
      46.9%, 46.2%, and 11.5%, respectively. In all subsamples, those with borderline
      personality were statistically significantly more likely to abuse prescription
      medication than those without the disorder. For example, borderline patients in
      the psychiatric sample were twice as likely to abuse prescription medications, in
      the predominantly primary care sample 4 times as likely, and in the internal
      medicine only sample nearly 6 times as likely. CONCLUSIONS: Regardless of
      setting, patients with BPD are at great risk for the abuse of prescription
      medications.

PMID- 19860071
TI  - Depression and diabetes among low-income Hispanics: design elements of a
      socioculturally adapted collaborative care model randomized controlled trial.
AB  - OBJECTIVE: This article describes design elements of the Multifaceted Depression
      and Diabetes Program (MDDP) randomized clinical trial. The MDDP trial
      hypothesizes that a socioculturally adapted collaborative care depression
      management intervention will reduce depressive symptoms and improve patient
      adherence to diabetes self-care regimens, glycemic control, and quality-of-life.
      In addition, baseline data of 387 low-income, 96% Hispanic, enrolled patients
      with major depression and diabetes are examined to identify study population
      characteristics consistent with trial design adaptations. METHODS: The PHQ-9
      depression scale was used to identify patients meeting criteria for major
      depressive disorder (1 cardinal depression symptom + a PHQ-9 score of > or = 10)
      from two community safety net clinics. Design elements included sociocultural
      adaptations in recruitment and efforts to reduce attrition and collaborative
      depression care management. RESULTS: Of 1,803 diabetes patients screened, 30.2%
      met criteria for major depressive disorder. Of 387 patients enrolled in the
      clinical trial, 98% had Type 2 diabetes, and 83% had glycated hemoglobin (HbA1c)
      levels > or = 7%. Study recruitment rates and baseline data analyses identified
      socioeconomic and clinical factors that support trial design and intervention
      adaptations. Depression severity was significantly associated with diabetes
      complications, medical comorbidity, greater anxiety, dysthymia, financial
      worries, social stress, and poorer quality-of-life. CONCLUSION: Low-income
      Hispanic patients with diabetes experience high prevalence of depressive disorder
      and depression severity is associated with socioeconomic stressors and clinical
      severity. Improving depression care management among Hispanic patients in public
      sector clinics should include intervention components that address self-care of
      diabetes and socioeconomic stressors.

PMID- 19860074
TI  - Influence of religion on sexual self-perception and sexual satisfaction in
      patients suffering from schizophrenia and depression.
AB  - OBJECTIVE: It is well documented that religion has an impact on mental health of
      both healthy people and mental health patients. However, scientific research
      regarding the influence of religion on sexual experiences and sexual self
      perception in mental health patients and healthy people is very scarce. GOAL:
      Therefore, our goal was to research how and in what measure religious and
      atheistic views of patients suffering from depression and schizophrenia and
      healthy people influence their sexual functions and sexual self-perception.
      SUBJECTS AND METHODS: This research was conducted on 100 patients suffering from
      schizophrenia and 100 patients suffering from depression, while 100 healthy
      individuals served as a control group. DMS-IV criteria were used when diagnosing
      schizophrenia and depression. In order to research the aspects of sexual self
      perception we used Bezinovic's questionnaire and Arizona sexual experience scale
      (ASEX) to research the aspects of sexual intercourse. RESULTS: Results show that
      Roman-Catholic patients suffering from schizophrenia experience greater sexual
      satisfaction than Eastern-Orthodox or atheist schizophrenic patients. Among
      patients suffering from depression in regard to their differing religious views
      there were no significant differences regarding sexual satisfaction or the
      aspects of sexual self-perception. Furthermore, there is a significant difference
      among healthy individuals when taking into consideration religious views. We
      established that Muslims have a significantly stronger sexual drive then
      atheists, Roman-Catholic or Eastern-Orthodox individuals. Compared to Roman
      Catholic and Eastern-Orthodox individuals, atheists have better consciousness of
      their own sexuality. CONCLUSION: We can conclude that religious views have an
      influence on sexual functioning and sexual self-perception of patients suffering
      from depression and schizophrenia and also healthy individuals. Thus, further
      research on a bigger sample of participants--not only of those religious
      denominations covered in this research, but also of those that are less present
      in our society and of other mental health disorders and illnesses--is needed.

PMID- 19860075
TI  - Adolescents' mental health in Abha city, southwestern Saudi Arabia.
AB  - Using stratified random sampling technique, 1552 adolescent school age boys and
      girls in Abha city, southwestern Saudi Arabia, were screened for mental health
      using Arabic validated version of SCL-90-R. The overall prevalence of mental
      disorders amounted to 15.5%. The most frequent mental symptoms were phobic
      anxiety (17.3%), interpersonal sensitivity (14.7%), and obsessive compulsive
      (14.5%). In logistic regression analysis, some sociodemographic conditions
      (father education, mother working status, ranking among brothers and sisters, and
      type of school) were significantly affecting mental health. General practitioners
      and other primary care workers need to be educated to better engage young people,
      to recognize mental disorders, and to deliver simple treatments, including
      supportive counseling, and cognitive behavior therapy. There is a need for a
      national program in the country to integrate youth mental-health interventions
      with all existing youth programs, including those in health and education.

PMID- 19860076
TI  - Delirium in children and adolescents.
AB  - OBJECTIVE: To study the clinical profile of children and adolescents (< or = 14
      years) referred to the Consultation-Liaison (CL) psychiatry services of a
      Tertiary Care Centre. DESIGN: Retrospective chart review. SETTING: Patients seen
      by the CL psychiatry services of Department of Psychiatry, Postgraduate Institute
      of Medical Education and Research, Chandigarh. PARTICIPANTS: Subjects diagnosed
      as delirium (as per ICD-10) during their inpatient stay was done. MAIN OUTCOME
      MEASURES: phenomenology of delirium and response to treatment. RESULT: Forty-six
      children and adolescents were diagnosed as delirium by the psychiatry
      consultation-liaison team. The most common underlying pathology was infection of
      various types, followed by neoplasms. All subjects exhibited sleep-wake cycle
      disturbance and impaired orientation. Other common symptoms were impaired
      attention (89.5%), impaired short-term memory (84.2%), agitation (68.4%), and
      lability of affect (60.5%). Delusions and hallucinations were reported by only a
      few patients. Most of the patients were treated with low dose haloperidol and
      they responded well. CONCLUSION: Sleep wake cycle disturbances and cognitive
      dysfunction are common in children and adolescents with delirium.

PMID- 19860077
TI  - Religious involvement and cigarette smoking among Iranian university students.
AB  - OBJECTIVES: To find out the prevalence of cigarette smoking in a group of Iranian
      Muslim students and also to find out if there is a relationship between religious
      practices and cigarette smoking. METHODS: In this cross-sectional study, 950
      university students in Kerman, Iran were asked to fill out a self-administered
      questionnaire consisting of questions on demographic data, cigarette smoking, and
      religious practices. It was explained that the study was anonymous and voluntary,
      and confidentiality was assured. RESULTS: All 833 subjects who participated in
      the study were Muslims, 54.1% of whom were female and 89.3% were single.
      Approximately 40% of male students and 5.8% of the female ones were smokers.
      Based on bivariate analysis, some differences were noted in the prevalence of
      smoking according to gender, marital status, income, average university scores,
      close friend's smoking, parental smoking, reading the Quran, saying prayers,
      mosque attendance, and fasting. Using multivariate analysis, male gender, higher
      income, lower average exam scores, and close friend's smoking being associated
      with the likelihood to smoke cigarettes. The odds ratio for cigarette smoking in
      the upper tertile compared with those in the lower tertile of religious activity
      was 0.53 (CI 95% 0.33-0.84). CONCLUSION: Religious activities may have a
      protective role against cigarette smoking among Muslim college students in the
      country.

PMID- 19860078
TI  - The role of cognitive impairment and caregiver support in diabetes management of
      older outpatients.
AB  - OBJECTIVES: To examine the role of cognitive impairment and caregiver support in
      diabetes care adherence and glycemic control. METHODS: Fifty-one veteran male
      outpatients (27 with caregivers) aged 60 years and older with type 2 diabetes
      were evaluated for cognitive impairment with the Cognitive Abilities Screening
      Instrument. Patients or caregivers completed diabetes self-care and depression
      scales. Medical morbidity information and HbA1c plasma levels at baseline and 1
      year later were obtained from electronic medical records. RESULTS: Greater
      cognitive impairment (F = 5.1, p < .05), and presence of a caregiver (F = 5.3, p
      < .05), were independently associated with worse diabetes care adherence
      (adjusting for age, education, medical comorbidity, and depression). In addition,
      Mean HbA1c levels were worse in the cognitively impaired group with caregivers
      relative to the three other groups (F = 4.10, p < .05, eta2 = .09). One year
      later, mean HbA1c levels rose from 7.7 to 8.2% in the cognitively impaired group
      with caregivers. CONCLUSION: Cognitive impairment is associated with worse
      diabetes care management. Surprisingly, the presence of a caregiver is not
      protective. Further research is necessary to examine the healthcare needs of
      cognitively impaired, diabetic patients and their caregivers.

PMID- 19860079
TI  - [Cognitive psychotherapy of social phobia and generalized anxiety disorder].
AB  - Recent years have seen a better understanding of the psychological changes
      underlying social phobia and generalized anxiety disorder, and successful methods
      of cognitive psychotherapy have been developed. Exposure to social situations
      causing anxiety and cognitive restructuring has diminished social anxiety. An
      underlying factor in generalized anxiety disorder is, among other things, a
      difficulty to deal with and tolerate uncertainty. Adaptation of distressing
      dysfunctional metacognitions has recently emerged alongside conventional
      cognitive-behavioral treatment modalities.

PMID- 19860080
TI  - [Home blood pressure measurement].
AB  - Hypertension, the leading global risk factor for early mortality, can not be
      detected or treated without accurate and practical methods of blood pressure (BP)
      measurement. Although home BP measurement enjoys considerable popularity among
      patients, the diagnosis and treatment of hypertension are still mostly based on
      office measurements. However, recent studies have shown that home BP is more
      strongly associated with hypertensive target-organ damage and future
      cardiovascular morbidity. Home BP measurement also allows the identification of
      white-coat hypertension. A paradigm shift is needed in BP measurement as evidence
      based medicine suggests that clinic BP measurement should mainly be restricted
      for screening purposes.

PMID- 19860081
TI  - [Obese adolescent].
AB  - Our lifestyle involving eating snacks and having little exercise promotes weight
      gain also in the young, especially if this is additionally favored by genetic
      factors. An intervention of weight gain restriction should be made as early as
      possible, with adequate time during the consultation to profoundly deal with the
      issue. Anamnesis and clinical examination usually suffice for diagnosis.
      Establishment of a confidential therapeutic relationship will require time and
      involvement. Possibilities for a quick treatment are not available, but a long
      term treatment plan with the young person is instead devised, setting partial
      goals that are small enough.

PMID- 19860082
TI  - [Myocardial infarction in a young patient--with underlying vasculitis].
AB  - Myocardial infarction in a young patient is rare, and its diagnosis and treatment
      may be delayed. Vasculitis can cause inflammation in the coronary artery and
      cause a myocardial infarction even in a young person. We describe a sudden
      myocardial infarction caused by vasculitis in two young adults having chest pain
      symptoms.

PMID- 19860083
TI  - [Evolution of pathogenic micro-organisms as a challenge for medicine].
AB  - Successful parasitic micro-organisms are able to adapt to the circumstances of
      the host's organ system, and it is usually not expedient for them to kill their
      host. Under selection pressure, the evolution of micro-organisms is vastly
      quicker that that of man. The selection pressure brought about by rapid
      ecological changes and alterations associated with human action provides for the
      development of new, dangerous pathogens and transformation of familiar pathogens
      to become more dangerous. Progress in molecular biology has thus far not yielded
      as many new tools for the treatment of infectious diseases as the hopes were in
      the early 2000's.

PMID- 19860084
TI  - [Evolution of psychosis].
AB  - Psychosis poses a major challenge for natural selection. The heritability of
      psychotic disorders is considerable and psychosis is associated with decreased
      reproductive success. Natural selection has not succeeded in eliminating the
      genes that predispose to the illness. Yet natural selection is considered to
      prune those features that decrease reproductive success. This paper deals with
      various evolutionary psychiatric models of major psychoses. According to Burns's
      model it is argued that psychosis may be the high price that humans have to pay
      for the evolution of their complex social brains. The same genes that have helped
      to shape our humanity carry the risk of psychosis. As such the genes would confer
      an evolutionary advantage, but their incremental effect would increase the risk
      of psychosis.

PMID- 19860085
TI  - [Evolution of teeth].
AB  - True teeth developed approximately 230 million years ago. Mammals have an
      accurate dental occlusion, whereby the renewal of teeth has reduced to two sets
      of teeth. Since the shape of teeth does not change after eruption, they form a
      good subject for developmental biology research. Research on fossil material and
      current ecology of mammals has opened up new perspectives into the research of
      tooth shape, food, ecology and climate.

PMID- 19860086
TI  - [Evolution of speech and hearing].
AB  - Actual spoken language of man developed only approximately 200,000 to 100,000
      years ago. As a result of natural selection, man has developed hearing, which is
      most sensitive in the frequency regions of 200 to 4000 Hz, corresponding to those
      of spoken sounds. Functional hearing has been one of the prerequisites for the
      development of speech, although according to current opinion the language itself
      may have evolved by mimicking gestures with the so-called mirror neurons. Due to
      hearing, gesticulation was no longer necessary, and the hands became available
      for other purposes.

PMID- 19860087
TI  - [Impact of parents' mental health disorders on psychiatric problems of the
      offspring].
AB  - Psychiatric disorders in mothers and fathers increase children's risks for
      psychiatric problems in childhood and adulthood. The chronicity and the impact of
      the disorder on the parent's interactional and functional capacities are more
      important than the diagnosis itself. Children's psychiatric disorders are more
      severe and chronic and they start at an earlier age than in families with parents
      without psychiatric disorders. Behavioral and anxiety disorders emerge in early
      childhood and school age, while depression and alcohol and drug abuse in
      adolescence. Children's needs for prevention and treatment are to be taken care
      of when their parents use psychiatric services.

PMID- 19860088
TI  - [Chronic inflammatory bowel diseases in children and adolescents].
AB  - Chronic inflammatory bowel diseases in children and adolescents Inflammatory
      bowel disease (IBD) is further increasing in children and adolescents in most
      Western countries including Finland. The etiologic factors of IBD and possible
      triggers have remained unclear. The clinical picture in paediatric IBD is more
      aggressive than in adults and operative intervention is common. Medical therapy
      is basically in line with the therapy used in adult patients. Optimal treatment
      is crucial in order to support normal growth and pubertal development. New
      serological and fecal analyses enhance the diagnostic accuracy and help the
      screening of the disease. The impact of IBD into the quality of life and
      psychosocial health has to be considered especially in severe cases.

PMID- 19860089
TI  - [Tinnitus].
AB  - Tinnitus is a symptom caused by the dysfunction of the auditory system associated
      with hyperactive networks of the central auditory tract. Intimate relationship of
      the auditory tract with the limbic system may lead to a stress reaction with
      subsequent sleep disturbances, distress and depression. The target of tinnitus
      treatment shoud be the annoyance caused by tinnitus, not the sensation itself.
      Optimally, all tinnitus patients should be treated according to the TRT
      principles including careful diagnostics, informational counceling and sound
      based therapies. Some patients need sleep therapy as well as anti-depressive
      therapy.

PMID- 19860090
TI  - [Scrotal masses in adulthood].
AB  - GPs often encounter patients with scrotal masses. Most of these are easily
      diagnosed by means of palpation and transillumination. Scrotal ultrasound is the
      primary radiological investigation, and should be done in cases of uncertain
      clinical diagnosis or when a solid mass in the scrotum is suspected. Benign
      processes such as hydrocele, spermatocele and varicocele are the most common
      causes for scrotal abnormalities. Symptomatic cases are treated with surgery or
      percutaneous sclerotherapy/embolization. Malignant testicular tumours, although
      less frequently seen, need prompt and accurate diagnosis and treatment. Radical
      orchidectomy is the primary treatment, followed by radiochemotherpy in selected
      cases.

PMID- 19860091
TI  - [Labor pains].
AB  - Every woman in labor shall have the right to receive effective analgesia if she
      so wishes. Management of labor pains should strive for individuality according to
      the mother's wishes, even if they are changing. The effect of epidural and spinal
      anesthesia is unmatched in pain management. Anesthesia may be given when labor is
      clearly under way, and can be continued even at the expulsive stage. With
      contemporary drug mixtures it is possible to carry on with the anesthesia
      throughout the delivery without significantly affecting its course.

PMID- 19860092
TI  - [Bent spine straightens up--a case of camptocormia].
AB  - Bent spine, i.e. camptocormia appears in several disease. Segmental dystonia is
      one of these. A few cases benefiting from botulinum toxin therapy have been
      described in the literature. We describe a case, in which segmental dystonia is
      associated with camptocormia, causing the patient to use a wheelchair. The
      condition fulfilled the criteria of both clinical and electromyographic dystonia.
      Administration of botulinum toxin into rectus abdominus muscles was started. The
      response was good: the patient was able to walk in a fairly erect posture
      assisted by a rolling walker.

PMID- 19860093
TI  - [Diabetes-related foot problems].
AB  - Foot ulcers due to neuropathy and/or ischemia, often complicated by infection,
      are a leading cause of hospitalisation and amputation in diabetic patients.
      Sensory neuropathy, foot abnormality, missing pulses and previous history of
      ulcers or amputation are risk factors for ulceration. Regular examination of feet
      and protective footwear reduce this risk. Off-loading the ulcer area promotes
      healing. Revascularisation improves the blood supply in cases where it has been
      compromised. Systemic antibiotics are only required in the case of acute foot
      infections and osteomyelitis with an underlying ulcer. Prevention and treatment
      of foot ulceration by multidisciplinary teams, including podiatric services,
      decreases amputations by up to 85%.

PMID- 19860094
TI  - Does a seasonal developmental rhythm exist in tropical living populations?
AB  - The main aim of this work concerns the answer a question whether the general
      regularity of seasonal differences in changes of height, weight and body
      components during ontogeny exist. If so, whether this phenomenon depends on
      cyclic changes in nature or this rather is an adjustment to local conditions and
      mode of life. To answer this question the studies took place in the tropical
      climate of Yucatan and included 49 boys and 47 girls aged 11-12 years and being
      of the Maya, Mestizo and Creole origin. The youths were attending two schools
      which were located in rather poor districts of Merida (capital city of the
      Yucatan State, Mexico). The investigations started in February 2002 and ended in
      November 2003 and were continued monthly. The standard anthropometric methodology
      was applied to measure body height, weight, arm, waist, hip and calf
      circumferences and five subcutaneous fat folds (biceps and triceps brachii,
      subscapular, suprailiac and calf). Bioimpedance techniques were used to measure
      fat mass (FM), fat free mass (FFM) and total body water (TBW). The results show
      that monthly or longer rates of stature increments and increments or declines of
      body mass do not exist. The similar observations were mentioned according to
      daily studies of similar type in literature. There are not similar regularities
      of changes even in groups of coevals of the same gender and within the youths
      coming from the same district. Each variable shows a quite specific rate of
      changes.

PMID- 19860095
TI  - Receiver operating characteristics (ROC) curve estimation of low birth weight
      based on maternal early third trimester weight among Bengalee women of Kolkata,
      India.
AB  - The cross-sectional hospital based study was undertaken to provide an efficient
      and useful cut off point of maternal early third trimester weight, for low birth
      weight (LBW), based on receiver operating characteristics (ROC) curve among
      Bengalee mothers of Kolkata, India. A total of 233 mother-baby pairs were
      included in the present analysis. The means for maternal age and weight were
      23.44 (SD = 3.88) years and 49.45 (7.19) kg, respectively. Means for gestational
      age and birth weight were 38.97 (1.12) week and 2664 (324) gm, respectively. The
      ROC curve analysis showed maternal weight < 48.0 kg as the best cutoff point of
      LBW. Data showed maternal weight < or = 48.0 kg had significantly higher OR (OR =
      2.92, 95% CI: 1.56-5.51) for delivering LBW baby. In conclusion, the cut-off
      point of maternal early third trimester weight < or = 48.0 kg could be used for
      nutritional intervention programs in order to combat LBW among this population.

PMID- 19860096
TI  - Anthropometric growth pattern in Ethiopian infants and children: an evaluation
      based on different international growth references.
AB  - At the population level international growth references have been widely used as
      useful tools to assess a number of situations, i.e.: to predict local and general
      emergencies related to food and nutrition; to assess the equity of distribution
      of economic resources within and between communities; to evaluate the suitability
      of weaning practices and to screen and following at-risk groups. Nevertheless,
      recently several concerns were raised regarding the adequacy of currently
      existing growth references involving study design, population sample, time
      validity, and evaluation of infant and children well-being in terms of food
      availability and nutritional adequacy. As in the past, discussion involve also
      suitability of local or national reverences versus the international ones. This
      paper focusses on the re-evaluation of the main auxometric indexes, i.e.: height
      for age, weight for height and BMI in a sample of infant and children aged
      between 24 and 120 months from urban and rural Ethiopia. Previous evaluation
      based on the NCHS-1977 growth references led to striking results in terms of
      growth retardation while a recent evaluation based on NCHS-2000 (NHANES) growth
      references gave better but contradictory pictures. As consequence, concerns on
      the adequacy of international references use in infant and children growth
      assessment in the developing countries seem to be widely justified while local or
      national well built growth references should offer the possibility for a most
      realistic evaluation.

PMID- 19860097
TI  - Exclusive breastfeeding and growth in Croatian infants--comparison to the WHO
      child growth standards and to the NCHS growth references.
AB  - The objective of this study was to compare the growth of exclusively breastfed
      infants and formula fed infants in eastern Croatia. Additionally, we compared
      growth patterns and estimated overweight based on the World Health Organization
      (WHO) child growth standards and the National Center for Health Statistics (NCHS)
      references. The growth of 88 Croatian infants in two feeding groups (44 breastfed
      and 44 formula fed) has been researched and presented. The feeding mode was
      obtained by the 24-hour dietary recall method. Anthropometric measurements were
      performed at birth and at 1, 2, 3, 4, 6, 9 and 12 months of age. There were
      significantly lower increases in weight and length in exclusively breastfed
      infants versus formula fed at 12th month (p < 0.05). The weight gain of
      exclusively breastfed infants was 665 +/- 886g, and among formula fed infants 72
      +/- 71254g, and also the exclusively breastfed infants showed significantly lower
      length gain (25. +/- 3.1 cm) than formula fed infants (27. +/- 3.1 cm) in the
      period from birth to the end of the first year. Differences shown in assessment
      of growth, depended of growth chart used WHO child growth standards or NCHS
      references. A larger number of overweight children were found in the formula fed
      group in comparison to both references, suggesting that exclusive breastfeeding
      prevents this occurrence. We conclude that breastfeeding provided the nutrients
      necessary for infants to keep with the WHO standards of regular growth in
      children.

PMID- 19860098
TI  - Regulatory T cells (Tregs) monitoring in environmental diseases.
AB  - The prevalence of environmental diseases is increasing worldwide and these
      diseases are an onerous burden both to the individual and to the public health.
      Urban air pollution is a grave problem in majority of metropolises, which contain
      high levels of traffic congestion generating great amounts of genotoxic
      substances. The contribution of such environmental exposure to increase
      prevalence of many allergic, environmental diseases and multiple chemical
      sensitivity or other related syndromes, as a result of an abnormal immune
      response based on environmental damage of lymphocyte subsets, is marked. Benzene
      is one of the most important air pollutants that are emitted by oil industry,
      since they are involved in almost every refinery process. Volatile organic
      compounds (VOCs) are a major group of air pollutants and play a crucial role in
      ecological damages, disturbing the ecosystem and human health. The variability of
      pollutants is an important factor in determining human exposure to these
      chemicals. The immune system possess a capacity to distinguish between innocuous
      and harmful foreign antigens and controls this action by mechanisms of central
      and peripheral tolerance, where crucial role play regulatory T cells (Tregs). We
      analyzed the characteristics of human Tregs of inhabitants living near gasoline
      industry which have assessed moderate spyrometric tests and compared them with
      those situated in rural areas. Our data demonstrate that the chronic inhalation
      exposure increases the percentage of Tregs cells, but contrary those of
      inhabitants with decreased spirometry values have shown diminished number of
      Tregs, which may contribute to the new therapeutic approach of environmental
      diseases.

PMID- 19860099
TI  - Sun exposure and visual field damage among children on the Adriatic Island Rab-
      possible initial risk factor in development of age-related macular degeneration.
AB  - The Adriatic Island Rab, situated in the northern part of the Croatian sea, is
      more strongly exposed to sunlight (especially from May to October) than the other
      parts of Croatia and most of the European countries. As consequences of higher
      solar radiation, significant percentage of Pseudoexfoliation of lens capsula
      occurs in 15% and fundus picture of AMD (Age-Related Macular Degeneration) in 18%
      of agriculturalists and fishermen (45-70 years old). We previously presented the
      first clinical study showing that in AMD the peripheral visual field is also
      damaged. In this clinical study we examined 68 children (8-15 years old),
      including following procedures: vision correction, slit lamp examination, visual
      field in technic of isopters and profile quantitative perimetry (meridian retinal
      thresholds examination) using Kowa automated perimeter. In 15% of examinees we
      found strictly foveal "degeneration", and changes of visual fields: higher
      meridian thresholds and typical changes with invagination of isopters. It is very
      interesting that these children with damaged visual field and fundus picture do
      not protect their eyes from the sunlight during summertime. We suggest the
      possibility of the influence of higher sun radiation as one of the risk factors
      in the earlier development of future AMD.

PMID- 19860100
TI  - Effects of obesity reduction on cardiovascular risk factors: comparison of
      individual and group treatment--substudy of the Croatian Healthy Weight Loss
      Programme.
AB  - Prevention of obesity may help reduce the morbidity and mortality from
      cardiovascular diseases. In Croatia, over half of adult population is overweight.
      Aldo the basic medical principles of healthy weight-loss programmes are well
      known, it is believed that mainly because of the leak of successful therapeutic
      approach obesity remains the most challenging changeable cardiovascular risk
      factor in nowadays clinical practice. Objective of this Croatian Healthy Weight
      Loss Programme substudy was to determine effects and differences between the
      intensive group and intensive individual weight-loss program on weight loss and
      cardiovascular risk factor. A clinical trial included 476 adults whose body mass
      index (BMI) was > 30 or > 28 accompanied by increased blood pressure, glucose,
      and cholesterol. The study participants completed either a group (n = 243) or
      individually-based (n = 233) 6-month weight-loss program consisting of education,
      low-fat diet, pharmacological treatment with orlistat, psychological counselling,
      and exercise. Body weight, body mass index, blood pressure, blood sugar, and
      blood cholesterol were measured in all participants after 3 and 6 months. The
      average weight loss was 12.2 (13%) kg and 7.6 (9%) kg in the group and individual
      program, respectively. Beside the weight reduction, the levels of blood
      cholesterol, glucose, and blood pressure were also significantly reduced in
      comparison with baseline, decreasing to normal values in all participants (P <
      0.001 for all). Decrease in the monitored parameters was greater in participants
      in the group program. The weight loss program provided a healthy loss of extra
      weight in the period of 6 months. The group program produced greater decrease in
      body weight, body mass index, blood pressure, glucose, and cholesterol than the
      individual program.

PMID- 19860101
TI  - The early prevention of metabolic syndrome by physical exercise.
AB  - The article deals with physical exercise in the early prevention of metabolic
      syndrome, which is one of the most frequent diseases today. Sedentary life style
      of modern man, surrounded by sophisticated technological achievements, supersedes
      the time spent in motion in all age groups, from the earliest childhood. The
      growing number of well substantiated studies has yielded results connecting such
      kind of life with greater incidence of many chronic diseases and low functional
      capability of an organism. Metabolic syndrome (MS) is a complex process and one
      of the most important groups of diseases, presenting a major health problem in
      developing countries. MS is an increasing risk for coronary heart disease, stroke
      and peripheral angiopathy. MS comprises overweight and abdominal
      (intraperitoneal) apple shape obesity, insulin resistance or glucose intolerance
      (type 2 diabetes mellitus--some persons are genetically predisposed to insulin
      resistance), hypertriglyceridemia with low HDL and high LDL cholesterol,
      accompanied by arterial hypertension. The prevention of metabolic syndrome should
      start as early as possible. Regarding physical activity, the period of childhood
      and adolescence is very important from the aspects of public health. However,
      intervention exercise programs should not be limited to younger age groups, but
      must encompass all age groups within population.

PMID- 19860102
TI  - Body composition and somatotype of the elite of Polish fencers.
AB  - The purpose of this study was to determine body composition and somatotype of the
      male fencers who were grouped by different fencing weapons. Analysis of body
      composition, with untrained men as background, will update the data necessary for
      the somatic profiles of fencers. Thirty contestants were examined during the
      Polish Fencing Championships in 2004. They took part in epee (n = 10), foil (n =
      10) and sabre (n = 10). They were aged 23.3 +/- 2.9; their length of training was
      12.6 +/- 2.5 years, with the frequency of training 15.9 +/- 3.1 hours per week.
      In each weapon style there were champions and vice-champions of Poland from the
      year 2004. Twelve of them were classified among the first fifty contestants
      according to the D'Escrime International Federation (FIE) ranking. An experienced
      evaluator performed 10 measurements necessary to designate somatotypes by means
      of Heath-Carter method and to estimate the percentage of body fat and
      composition. Sabre fencers (weight = 84.4 kg, somatotype = 3.4-5.4-1.8) were
      heavier than both epee fencers (77.9 kg, 3.6-4.9-2.5) and foil fencers (74.9 kg,
      2.9-4.2-2.8). Sabre specialists had higher mesomorphy than foil fencers (ANOVA
      and Bonferroni's multi comparison test). Sabre fencers were characterized by
      higher fat free mass and a higher BMI and fat free mass index than fencers of the
      other two weapons. Discriminant analysis result was significant (p < 0.01) with a
      relative percentage with a 72.4 and a canonical correlation coefficient 0.692,
      and Wilks' lambda = 0.385. Amongst the 30 observations used to fit the model, 22
      (73.3%) were correctly classified. Against the background of non-training men,
      fencers were distinguished by a higher body weight (79.0 vs. 72.1 kg, t = 3.97, p
      < 0.001) and a higher height-weight ratio (43.21 vs. 42.46, t = 2.24, p < 0.05).
      Fencers' somatotypes differed from the somatotypes of the untrained (3.3-4.8-2.3
      vs. 3.7-4.3-3.1). They were characterized by their higher mesomorphy (t = 2.10, p
      < 0.05) and lower ectomorphy (t = 3.48, p < 0.01), as well as greater adiposity
      (16.8 vs. 15.7%, t = 2.03, p < 0.05).

PMID- 19860103
TI  - Relations between morphological and cognitive dimensions of persons with above
      average motor abilities.
AB  - The set of 33 anthropometric measures and the battery KOG3 to estimate the
      perceptive, serial and parallel processors were applied on the sample of 217
      students of the Faculty of Sport and Physical Education in Novi Sad (Serbia). By
      means of factor analysis with the oblimin rotation, the following morphological
      dimensions were obtained and analyzed: 1) longitudinal skeletal dimensionality,
      2) transversal skeletal dimensionality, 3) volumen and body mass, 4) subcutaneous
      fat and 5) head voluminosity. After the transformation of the results from linear
      model of the relations into the non-monotonous spline function of the forth
      degree, the results of correlation, canonical correlation and redundancy analyses
      were subjected to the non-linear model analysis. The obtained results showed that
      the non-linear model of data analyses indicated more significant relations and
      explained better the common variance of the two sets of variables.

PMID- 19860104
TI  - Position specific morphological characteristics of elite water polo players.
AB  - The aim of the study was to determine morphological characteristics of elite
      water polo players. In a sample of 121 water polo players, the structure of a set
      of 23 morphological space variables was determined by use of factor analysis,
      followed by determination of differences between all pairs of playing positions
      in the manifest morphological space by use of Post Hoc analysis. Factor structure
      indicated the presence of four basic superior latent dimensions responsible for
      directly measurable manifestations of morphological parameters: first component
      acting as a general mechanism of growth and development; second component being
      bipolar, at one pole almost exclusively determined by adipose tissue, and on the
      other pole by longitudinal skeletal growth; third component differentiating
      longitudinal skeletal growth accompanied by subcutaneous adipose tissue from
      muscle mass development and transverse skeletal growth; and fourth component
      mostly differentiating transverse skeletal development relative to longitudinal
      skeletal development. Oblimin transformation of the main components was employed
      to define the factor of circular dimensionality, factor of subcutaneous adipose
      tissue, factor of longitudinal skeleton dimensionality, and factor of transverse
      skeleton dimensionality. Results of obtained by the analysis of variance (ANOVA)
      and homogenization of playing positions in water polo for each individual
      variable upon Post Hoc analysis yielded significant differences both within and
      between groups in all anthropometric variables except for the variable of triceps
      skinfold. Statistically significant differences were recorded between two groups
      of playing positions, i.e. centers and backs versus goalkeepers, wingers and
      outside forwards. Significant differences were found between water polo players
      playing at center and back positions, characterized by higher values of all
      measures of longitudinal and transverse skeleton dimensionality in comparison
      with water polo players playing at other positions (goalkeepers, wingers and
      outside forwards). Significant differences were observed according to body mass
      and volume between water polo players playing at center position, characterized
      by considerably higher values of all measures in comparison with water polo
      players at other positions, and between centers and backs versus other positions
      according to body weight, chest circumference and forearm circumference.
      Considering subcutaneous adipose tissue, skinfold variable was significantly more
      pronounced in water polo players playing at center position than in those playing
      at other positions.

PMID- 19860106
TI  - One year efficacy and safety of oral sildenafil treatment in severe pulmonary
      hypertension.
AB  - Severe pulmonary hypertension is a progressive disease which leads to limitations
      of functional status and poor survival. We evaluated efficacy and safety of a
      short (3 months) and a long term (12 months) sildenafil treatment in patients
      with severe pulmonary hypertension. We treated 12 patients with pulmonary
      hypertension with oral sildenafil. Patients were followed at three time points,
      at baseline, and after 3 and 12 months of treatment. Primary end point was
      improvement in functional exercise capacity assesed by 6-minute walk test, and
      secondary end points were changes in right ventricle hemodynamics. We found
      significant improvement in 6-minute walk test distance from 357 +/- 193 m at
      baseline to 431 +/- 179 m after three months and further improvement to 501 +/-
      159 m after 12 months (p < 0.01); decrease in right ventricule pressure from 107
      +/- 42 mmHg at baseline to 87 +/- 32 mmHg after 12 months (p < 0.01); and,
      decrease in right ventricule diameter from 3.2 +/- 1.1 cm to 2.76 +/- 0.86 cm
      after twelve months (p < 0.01). Drug-related adverse events were mild and
      transient in our group of patients. Long-term (12 months) sildenafil treatment is
      effective and safe in our patients with idiopathic and chronic thrombo-embolic
      pulmonary hypertension.

PMID- 19860105
TI  - Mechanical ventilation in chronic obstructive pulmonary disease patients,
      noninvasive vs. invasive method (randomized prospective study).
AB  - Acute respiratory failure due to chronic obstructive pulmonary disease (COPD)
      presents an increasing problem throughout the world. The aim of this study was to
      compare invasive and non-invasive mechanical ventilation (MV) for patients with
      COPD. A prospective, randomized trial was performed in a multidisciplinary
      intensive care unit for the period of 36 months and included 156 patients with
      COPD. MV procedure was performed using standard methods, and was applied as
      either invasive MV (IMV) or noninvasive MV (NIMV). Patients were randomized in
      two groups for application of MV using closed, nontransparent envelops.
      Comparison was made based on patient characteristics, objective parameters on
      admission and 1h, 4h, 24h, and 48h after admission and based on treatment
      outcome. We have confirmed that NIMV method is superior to IMV for patients with
      COPD. MV duration NIM:IMV was 94:172 hours, p < 0.001, time spent in Intensive
      Care Unit 120:223 hours, p < 0.001. Ventilator associated pneumonia
      5(6%):29(37%), p < 0.001. The advantage of NIMV in COPD patients, especially in
      the early stages was confirmed.

PMID- 19860107
TI  - Sonographic evaluation of pleural fluid in a large group of adult healthy
      individuals--end trial results.
AB  - This partly prospective, partly retrospective trial was performed in adult
      healthy volunteers to confirm the prevalence of sonographically visible
      physiological pleural and to establish possible individual variations of the
      presence and amount of pleural fluid over time as well as to asses relations in
      between pleural fluid and individual characteristics like age, sex, body mass
      index, smoking history and hormone therapy (in woman). A reliable threshold
      between normal and pathological pleural fluid findings was determined.
      Prospective chest sonography of both pleural spaces was performed with 3-12 MHz
      transducer in 71 randomly selected healthy adults and presence of pleural fluid
      was evaluated and measured as an anechoic layer at least 2 mm in thickness. Each
      individual was reexamined three times in two to four months intervals. Another 86
      individuals were prospectively re-examined for the third time, 24 to 36 months
      after completed previous trials while the data on the baseline and follow up
      examination were retrospectively acquired. Maximum thickness of the pleural fluid
      was measured in the elbow position after five minutes leaning in lateral
      decubitus position. Examinees served as their own controls, with the quantitative
      measurement of the fluid layer over time. The fluid layer was visible in at least
      one pleural space in 51/157 (32.5%) subjects, whereas 35 (22.3%) examinees had a
      positive finding on all three examinations. Consistency of this finding was high
      between each pair of examinations over time (Cohen's Kappa > or = 0.8, p <
      0.001). The maximum thickness of fluid layer ranged from 2.0 to 5.2 mm, with a
      mean of 2.9 mm independently of left or right pleural space and unilateral or
      bilateral presence. Regression models indicate that odds for observing pleural
      fluid in an individual decrease with age ( p = 0.013) and that if observed, the
      fluid tends to be thicker in women ( p = 0.017) and in subjects with higher BMI (
      p = 0.028). Sonography detected small amounts of pleural fluid in 32.5% of
      healthy individuals. If present, maximum thickness of the fluid layer doesn't
      exceed the threshold value of 5.2 mm with mean values around 3 mm. The amount of
      physiological pleural fluid is relative stable over time and is very likely an
      individual characteristic with lower frequencies in elders while the frequencies
      of sonographically detected pleural fluid in healthy adults does not correlate
      with sex, obesity, smoking or hormonal therapy.

PMID- 19860108
TI  - Comparative analysis of hepatocellular carcinoma in men and dogs.
AB  - Concerning the important differences in the ethiopathology of hepatocelular
      carcinomas (HCC) in humans and dogs, our work describes the expression of
      epidermal growth factor receptor (EGFr), cytokeratine 19 (CK19), vascular
      endothelial growth factor (VEGF) and transforming growth factor beta receptor
      (TGFbeta-r) in tumors arising in both species. Investigation included 25 cases of
      human and 8 cases of dog tumors. All human cases were noted in cirrhotic livers,
      while in dogs the tissue adjacent to tumor was not changed. In humans in two
      cases hepatitis B virus (HBV) and in one case hepatitis C virus (HCV) were
      determined. Investigation showed lack of TGFbeta-r reaction in six cases of
      canine HCC, while in humans only one case was negative. In most tumors specific
      hepatocyte antigen Hepatocyte Paraffin 1 marker (Hep Par 1) was mainly positive
      with markedly decreased reaction compared to the normal hepatocytes, while
      cytokeratine 19 for billiary epithelium was negative. The result of our
      investigation rise the question about the possible role of tumor suppressor gene
      TGFbeta-r in the development of HCC in dogs and in the same time emphasizes its
      importance in human diseases.

PMID- 19860109
TI  - Persistent accumulation of 4-hydroxynonenal-protein adducts in gastric mucosa
      after Helicobacter pylori eradication.
AB  - Recent studies indicate that oxidative stress caused by Helicobacter pylori and
      insufficient host antioxidant defense could play important role in pathogenesis
      of gastrointestinal ulcerations. By specific monoclonal antibodies we have
      detected weak presence of the major lipid peroxidation bioactive marker 4
      hydroxynonenal (HNE) in healthy human gastric mucosa, which strongly increased in
      case of H. pylori-associated peptic ulcer. Considering physiological presence of
      HNE on one hand, and high prevalence of H. pylori associated disorders on the
      other, evaluation of oxidative stress after treatment is important. Therefore, in
      current study immunohistochemical accumulation and distribution of HNE-protein
      adducts in gastric mucosa was evaluated with 21 patients having H. pylori
      associated duodenal peptic ulcer (DPU) before and one month after eradication of
      H. pylori. Although dramatic decrease in histological manifestations of
      inflammation was demonstrated after eradication of H. pylori, initially high
      immunopositivity for the HNE-protein adducts remained elevated in antrum and even
      increased in stomach corpus. The observed accumulation and redistribution to
      higher grades of HNE-immunopositivity in nuclei of glandular cells in gastric
      corpus indicate augmentation of oxidative stress after treatment and open
      possibilities for adjuvant antioxidant treatments to protect gastric mucosa from
      progressive oxidative stress after eradication of H. pylori infection.

PMID- 19860110
TI  - PhysioSoft--an approach in applying computer technology in biofeedback
      procedures.
AB  - The paper presents description of original biofeedback computer program called
      PhysioSoft. It has been designed on the basis of the experience in development of
      biofeedback techniques of interdisciplinary team of experts of the Department of
      Health Psychology of the University of Applied Health Studies, Faculty of
      Electrical Engineering and Computing, University of Zagreb, and "Mens Sana",
      Private Biofeedback Practice in Zagreb. The interest in the possibility of
      producing direct and voluntary effects on autonomic body functions has gradually
      proportionately increased with the dynamics of abandoning the Cartesian model of
      body-mind relationship. The psychosomatic approach and studies carried out in the
      50-ies of the 20th century, together with the research about conditioned and
      operant learning, have proved close inter-dependence between the physical and
      mental, and also the possibility of training the individual to consciously act on
      his autonomic physiological functions. The new knowledge has resulted in the
      development of biofeedback techniques around the 70-ies of the previous century
      and has been the base of many studies indicating the significance of biofeedback
      techniques in clinical practice concerned with many symptoms of health disorders.
      The digitalization of biofeedback instruments and development of user friendly
      computer software enable the use of biofeedback at individual level as an
      efficient procedure of a patient's active approach to self care of his own
      health. As the new user friendly computer software enables extensive
      accessibility of biofeedback instruments, the authors have designed the
      PhysioSoft computer program as a contribution to the development and broad use of
      biofeedback.

PMID- 19860111
TI  - Correlation of APACHE II and SOFA scores with length of stay in various surgical
      intensive care units.
AB  - The aim of this study was to evaluate the usefulness of using Acute Physiology
      and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure
      Assessment (SOFA) score as the predictors of length of stay (LOS) in various
      surgical intensive care units (ICUs) and to test the hypothesis that the
      significance of scoring for predicting LOS is greater in specialized surgical
      ICUs. We scored patients in a non-specialized general surgical ICU (n = 328) and
      in a specialized cardiosurgical ICU (n = 158) consecutively on admission (APACHE
      II-1st day; SOFA-1st day) and on third day of stay (APACHE II-3rd day; SOFA-3rd
      day) in a 4-month period. LOS and APACHE II/SOFA scores were significantly
      correlated both on admission and on third day of stay in the general surgical ICU
      (APACHE II-1st day r = 0.289; SOFA-1st day r = 0.306; APACHE II-3rd day r =
      0.728; SOFA-3rd day r = 0.725). LOS and APACHE II on admission were not
      significantly correlated in the cardiosurgical ICU (APACHE II-1st day r = 0.092),
      while SOFA on admission and APACHE II and SOFA on third day were significantly
      correlated (SOFA-1st day r = 0.258; APACHE II-3rd day r = 0.716; SOFA-3rd day r =
      0.719). Usefulness of scoring for predicting LOS in ICU varied between different
      surgical ICUs. Contrary to our hypothesis, scoring had greater value for
      predicting LOS in the non-specialized general surgical ICU. APACHE II score on
      admission had no value for predicting LOS in the cardiosurgical ICU.

PMID- 19860112
TI  - Health related quality of life regarding to gender in sarcoidosis.
AB  - Evaluation of the health-related quality of life (HRQoL) in patients with
      respiratory diseases has been increasingly included into regular clinical
      studies, and HRQL in sarcoidosis has been evaluated since not a long ago. The aim
      of the study was to evaluate HRQoL in patients with sarcoidosis regarding gender
      differences, pre and after therapy. We investigated 202 pathohistologically
      verified sarcoidosis patients (154 female and 48 male) without comorbidities.
      HRQL was assessed by the disease-specific Sarcoidosis Health Questionnaire (SHQ),
      which contains 29 items, and cover three domains: everyday functioning, physical
      activities and emotional state. Total score, as well as the scores for each SHQ
      domains were calculated. HRQoL was estimated pre and after three months of
      therapy. At the study start, the lowest score value for the whole group was
      reported in SHQ emotional state domain (4.24), and the highest in domain of
      physical functioning (4.7). After three months, the lowest values were reported
      in domain of everyday activities, while the highest scores were found in
      emotional domain; all SHQ scores increased, but reached the statistical
      significance only in the everyday functioning and the physical activities
      domains. Analyzing mean SHQ scores in male and female sarcoidosis pts before
      therapy we found high statistically lower emotional and total score in female
      pts, as well as lower physical score. After the three months therapy we found
      high statistical difference in physical domain (i.e. women had lower physical
      score than men). Female sarcoidosis pts showed lower emotional, physical and
      total score before therapy. After the three-month therapy we found that women had
      lower physical score than men. SHQ showed good measurement properties both in the
      cross-sectional and longitudinal assessment of sarcoidosis patients.

PMID- 19860113
TI  - The Croatian version of the Oral Health Impact Profile Questionnaire.
AB  - Purpose of this study was to develop a Croatian version of the Oral Health Impact
      Profile questionnaire (OHIP--CRO49), following the accepted cross-cultural
      adaptation technique guidelines. The original version was translated by using a
      forward-backward translation method. The psychometric properties of the OHIP
      CRO49 were tested. To test the construct validity 163 randomly selected subjects
      and 26 prosthodontic patients participated. The construct validity was supported
      by the association between the OHIP-CRO49 sum-scores and the self-reported oral
      health and five oral disorders. The test-retest reliability was tested on 30
      prosthodontic patients and 30 students, and it was supported by high intraclass
      correlation coefficients (r = 0.63 to 0.95). To test the internal consistency 163
      randomly selected subjects (general population), 26 prosthodontic patients and 29
      dental students participated, and it was supported by high Cronbach's alpha
      coefficients (0.60 to 0.97). The resposiveness was tested on 21 patients with a
      treatment demand (toothache), and was supported by a statistically significant
      mean OHIP-CRO49 score difference (from 108.48 to 27.57) and a high effect size
      (2.96 and 3.48). Adequate psychometric properties in a typical patients'
      population make the new instrument suitable for assessment of Oral health-related
      quality of life (OHRQoL) in Croatia.

PMID- 19860114
TI  - Optoelectronic pantography diagnostics of temporomandibular disorders in patients
      with bruxism.
AB  - Temporomandibular disorders (TMD) is a joint term that encompasses a number of
      clinical symptoms that involve the teeth, masticatory musculature and
      temporomandibular joints (TMJ). They are a frequent cause of orofacial medical
      conditions. The aetiology of disorders is complex and individual etiologic
      factors are not sufficiently defined. Bruxism, in its centric or eccentric form,
      is becoming a frequent problem for dentists. The purpose of this study is to show
      factors of the condyle leading in patients with bruxism by optoelectronic
      pantography, and to establish the possibility of using optoelectronic pantography
      in the diagnostic procedure of TMD. Patients were selected (N = 42), with
      incomplete sets of teeth, without prosthodontic appliances and with traces and
      symptoms of TMD. After completing the history questionnaire a clinical check up
      and plaster cast analysis patients with bruxism were selected (N = 22) and
      without bruxism (N = 20). During the study optoelectronic String-condylocomp LR3,
      Dentron, D-Hochberg (software JAWS 30) was used. This study showed the
      possibility of applying optoelectronic pantography in TMD diagnostics and
      compares history, clinical and condylographic parameters in TMD patients with and
      without bruxism. Optoelectronic pantography enables us, by using relatively easy
      methods, to determine a more accurate diagnosis, highly important when choosing
      therapeutic methods and control of the aforementioned disorders.

PMID- 19860115
TI  - Localization of mental and mandibular foramens on the conventional and digital
      panoramic images.
AB  - The purpose of this study was to compare the efficiency of conventional and
      digital panoramic images for localization of mental and mandibular foramens. Six
      dry edentulous human mandibles were used in the study. Conventional and digital
      panoramic images were obtained and the vertical and horizontal measurements were
      performed for localization of mental and mandibular foramens on the images. The
      correlations between radiographic (conventional and digital) and direct
      measurements were compared. A measurement error between the radiographic and
      direct measurements was determined at the level of 1 mm. The measurement errors
      were generally less in conventional panoramic radiography than digital one. There
      was statistically strong positive correlation between direct and radiographic
      measurements. Statistically significant difference was found between radiographic
      and direct measurements for bone height of mandible in ramus region. According to
      the results of this study, diagnostic performance of conventional and digital
      panoramic images seems to be equal for the localization of mental and mandibular
      foramens. The vertical radiographic measurements are generally reliable and
      correlated with direct measurements in mandible for conventional and digital
      panoramic radiography, but the evaluation of bone height in ramus region may not
      be sufficiently reliable.

PMID- 19860116
TI  - Influence of chronic stress and oclusal interference on masseter muscle pain in
      rat.
AB  - This study aimed to investigate the individual effects of chronic stress and
      occlusal interference, as well as their combined influence on masseter muscle
      pain. Experiments were performed on 28 male Wistar rats. Animals were submitted
      to chronic stress procedure, exposed to occlusal interference, or exposed to both
      mantioned procedures. At the end of the procedure animals were submitted to
      orofacial formalin test, and nociceptive behavioral response was evaluated.
      Statisticaly significant difference of nociceptive behavioral response in
      chronicaly stressed rats and in the animals with occlusal interference in
      comparation to the control group were not obtained (p > 0.05). In contrast,
      nociceptive behavioral response was significantly increased in rats submitted to
      both of experimental procedures (p < 0.01). These findings suggest that only
      combination of occlusal interference and chronic stress influence masseter muscle
      pain.

PMID- 19860117
TI  - Salivation quantum--stomatopyrosis--autogenic training.
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. 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. 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. 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, and to the reduction
      of dryness in the mouth.

PMID- 19860118
TI  - Biological aspects of the development and self-concept in adolescents living in
      single-parent families.
AB  - In this study we investigate whether there are differences between adolescents
      who grow up in single-parent families and those who grow up in nucleus families.
      We have decided that there are no differences in the physical development between
      the adolescents who are growing up in single parent families and those growing up
      in nucleus families. There is no difference in the self-concept between these two
      groups, except in the ethical and moral self-image of adolescents living with one
      parent. Adolescents living in single-parent families have a weaker moral self
      image. It can thus be concluded that physical development and positive self
      concept (a favorable image of oneself) in adolescents do not depend on whether an
      adolescent is growing up in a single-parent or a nucleus family, but on the
      different characteristics of parents and their relationship with children,
      whether they are married or not. For the children development the best is healthy
      marriage of their parents.

PMID- 19860119
TI  - Aggression in group psychoanalytic psychotherapy: questionnaire development (GA
      AG).
AB  - The aim of this study is developing of a questionnaire that observes aggression
      in group psychoanalytic psychotherapy and examines its factor structure. The
      questionnaire comprised of 160 statements in five-point Likert-type scale was
      developed through analysis of the content of aggressive communication among
      patients during group sessions. The questionnaire was applied on 253 patients
      that attended 40 small therapy groups in 9 cities in Croatia. All 20 group
      analysts are trained in the Institute for Group Analysis Zagreb. The patients
      were selected based on indications for group analysis. Two parallel questionnaire
      forms were designed of 80 items that were isolated through assessment of item
      discrimination and principal components analysis limited to five factors. A new,
      reliable and valid questionnaire that can be employed in group psychotherapy has
      been developed. The following has been isolated through factor analysis: 1.
      Difficulty in communication, 2. Distrust in the group therapist and the group, 3.
      Withdrawal from relationships and communication, 4. Low containing capacity, and
      5. Mutual lack of understanding. This questionnaire can measure the level of
      difficulty in communication, distrust in the therapist and the group, passive
      aggression, containing capacity, lack of understanding among group participants
      and in the group as a whole.

PMID- 19860120
TI  - Psoriasis, mental disorders and stress.
AB  - Etiology of psoriasis is still not known and comprises a range of assumptions and
      very complex etiological and pathogenetic mechanisms. Along with genetical
      predisposition, mental disorders and stresses might have a key role in the
      occurrence of this disease. Total number of 70 patients suffering from psoriasis
      were included in the investigation. Generally accepted structured clinical
      interview (SCID - The Structured Clinical Interview for DSM-IV) was applied in
      diagnostics of mental disorders. Various mental disorders were found in as many
      as 90% of patients suffering from psoriasis. The most frequent mental disorders
      were depressive disorder (19.2%), the posttraumatic stress disorder (17.8%),
      alcoholism (16.4%), adaptation disorder (15.1%), anxiety - depressive disorders
      (13.7%) and generalized anxious disorder (9.6%). The authors have concluded that
      in patients with psoriasis both various mental disorders and various stress
      events are frequent. The results have implied that there is a link between
      psoriasis on the one hand and various mental disorders and various stressors on
      the other. The investigation implies that there is a need to improve
      multidisciplinary approach in diagnostics and treatment of psoriasis and multi
      disciplinary team should consist of dermatologist, psychiatrist and psychologist.

PMID- 19860121
TI  - Forensic aspects of alcohol abuse and homicide.
AB  - Numerous investigations indicate a close link between violent behavior, homicide
      (murder) and alcohol intoxication. With increased frequency of drinking and the
      chronic consummation of alcohol, the risk of the fatal outcome or homicide and
      victimization caused by violence is more likely to occur. Studies conducted on
      convicted murderers suggested that about half of them were under the heavy
      influence of alcohol at the time of perpetration of murder. The sample in this
      survey consisted of 177 male offenders which committed criminal act of murder in
      Croatia from the year of 1990 until 2007 (capital murder and attempted murder).
      All were assigned for the forensic psychiatric evaluation by the Criminal Justice
      System (Court of Law) at the Department of Forensic Psychiatry, Neuropsychiatric
      Hospital, Popovaca, Croatia. For the purpose of this work the sample is divided
      in two groups of subjects: 1) offenders which were intoxicated at the time of
      murder and committed offence on intoxicated victim 2) offenders who were sober
      and committed offence on sober victims. Groups are compared according to the
      variables of crime and history of alcohol abuse. On the basis of obtained results
      we can conclude that there are significant differences in relation to the
      variables and modalities of criminal offence between two groups of offenders and
      victims. We could conclude that alcohol intoxication in offenders and victims at
      the time of murder could strongly affect the modalities of murder.

PMID- 19860122
TI  - Anterior neurodecompression of kyphotic spondylogenic myelopathy Ranawat grade
      III and posterior decompression of lordotic spine improve walking ability.
AB  - Cervical spondylosis is common condition rarely associated with
      radiculomyelopathy which surgical treatment, according to meta-analysis, is not
      better than nonsurgical. Our hypothesis was that neurodecompression which type is
      chosen according to spinal alignment should result in better functional
      improvement comparing with nonsurgical treatment. Between January 1, 1998 and
      December 31, 2007 a total of 77 patients with spondylogenic myelopathy were
      selected for the study. The inclusion criteria were symptoms and signs of
      myelopathy Ranawat grade III. Exclusion criteria were amyotrophic lateral
      sclerosis (ALS) and multiple sclerosis (MS). The curvature of the cervical spine
      was determined by Ishihara index. Anterior corpectomies and fusion was performed
      in the kyphotic spines, laminectomy with fusion in patients with neutral
      position, and open door laminoplasty in lordotic spines. Clinical improvement was
      assessed as differences between preoperative and 1-year follow up Nurick,
      modified Japanese Orthopedic Association (mJOA) myelopathy scales and walking
      test. Preoperative and postoperative transverse cord area and subarachnoid space
      were measured. Forty-four male and 31 female patients were surgically treated.
      Two patients with electrophysiological signs of ALS were excluded. Preoperative
      and postoperative mean +/- SD mJOA index was 9.15 +/- 1 and 13.01 +/- 1.4 (p <
      0.001), Nurick grading scale 3.05 +/- 0.7 and 1.8 +/- 0.6 (p < 0.001), walking
      time (sec) 64.4 +/- 3.2 and 46.2 +/- 3.3 (p < 0.001), and number of steps 69.7 +/
      4.4 and 57.6 +/- 2.8 (p < 0.001) respectively. Preoperative and postoperative
      transverse cord area (mean +/- SD, mm2) was 46.7 +/- 5.4 and 60.2 +/- 2.6 (p <
      0.001), and subarachnoid space 48.0 +/- 4.9 and 68.8 +/- 8.5 (p < 0.001)
      respectively. Our results showed that surgical treatment is beneficial for
      patients with spondylogenic myelopathy.

PMID- 19860123
TI  - Arthroscopic removal of metal foreign bodies from the knee joint after explosive
      war injuries.
AB  - The results of arthroscopic removal of metallic fragments from knee joint due to
      explosive war injuries are presented. In period from 1991-1995 during war in
      Croatia we have operated 25 knee joints. Indications for arthroscopy were based
      on radiographic and clinical findings. The foreign bodies in the joint were found
      in 19 patients while additional 6 had foreign bodies in the periarticular soft
      tissues. Arthroscopies were performed on average one month after wounding. The
      foreign bodies were placed in different parts of the joint with no prediction
      sites. In 8 knees foreign bodies were freely mobile, and in 11 were anchored to
      different intraarticular structures. There were no complications during early
      postoperative period as well as in follow up period.

PMID- 19860124
TI  - Vertebroplasty for vertebral compression fracture.
AB  - The patients with intensive pain caused by the vertebra body fracture were
      treated by application of bone cement under local or general anesthesia, by means
      of diascopy through unilateral transpedicular approach. The intensity of pain was
      followed-up on the VAS scale before surgery, 24 hours after surgery and three
      months after surgery. The cement was applied in 55 patients (43 women, 12 men).
      The average age of the tests was 68.43 years (38 to 82 years). Fifty five
      procedures were implemented on 85 vertebrae, i.e. 32 metastatic fractures and 23
      osteoporotic fractures. The procedures were applied on 28 thoracal and 57 lumbar
      vertebrae. The average VAS before surgery was 8.36 and 2.23 (p < 0.005) 24 hours
      after surgery, and it remained almost unchanged three months later. There were 1
      serious complication, a paraparesis caused by the leakage of cement into the
      spinal canal, which was partially recovered after decompression and
      rehabilitation treatment, and 2 superficial infections with S. epidermidis which
      were cured by means of antibiotics. By means of Wilcoxon paired test a
      significant difference was found between the preoperative VAS and the value 24
      hours after surgery (n = 55, Z = 6.451, p < 0.00001) and 3 months after surgery
      (Z = 6.45, p < = 0.00001), while there was a compliance between two VAS
      measurements after surgery (Z = 1.308, p = 0.191) which indicates that the fast
      pain reduction remained stable during the 3 month follow-up. The vertebroplasty
      is a safe and efficient surgical method in treatment of compressive vertebrae
      fractures which do not react to the conventional method of treatment. The
      achieved analgesic effect 24 hours after surgery is a good predictor of pain
      intensity 3 months after surgery.

PMID- 19860125
TI  - Microincision aponeurotic ptosis surgery of upper lid.
AB  - The paper is a prospective study of 23 lids of 20 patients with upper lid
      aponeurotic ptosis operated using microincision technique in period 2005-2008.
      There were 7 males and 13 females. Age of the patients was 28-83 years (y),
      average 61 +/- 17 y, for female 63 +/- 13.4 y and for male 61 +/- 19 y. Inclusion
      criteria were: aponeurotic upper lid ptosis more than 2 mm, no other lid
      abnormalities, minimal dermatochalasis, no previous or concomitant lid surgery.
      The procedure was performed in local anesthesia through 10 mm cut. Aponeurosis
      was fixated to the tarsal plate with two sutures. Success was considered if
      operated lid height differed up to 0.5 mm of the other eye and margin-to-reflex
      distance was 2-4 mm in primary position. Postoperative results regarding contour,
      skin crease and lash position were good in all patients. Regarding height, 19/23
      (83%) met criteria of 0.5 mm of the other eye and MRD 2-4 mm. In one bilateral
      procedure there was an asymmetry of 1 mm. Three patients with unilateral
      procedure had at least 1mm asymmetry comparing to the other eye. Reoperation was
      neccessary in two bilateral cases. Lid fold was symmetrical only in 7 patients
      (35%). The rest had slight to grose lid fold asymmetry. Complications were
      scarce, in early postoperative period there was hematoma in two patients lasting
      up to three weeks. Late failure was noticed in two cases 6 and 8 months
      postoperatively. Advantages are: less anesthetic results in less decreased
      levator function and more accurate assessment of eyelid position
      intraoperatively, less distortion of the lid due to less bleeding and edema,
      shorter operation time, less scarring and shortened recovery time. However it can
      be used only in selective cases.

PMID- 19860126
TI  - Comparison of proliferation and differentiation of calvarial osteoblast cultures
      derived from Msx2 deficient and wild type mice.
AB  - We analyzed proliferation and differentiation of calvarial osteoblasts derived
      from Msx2 deficient in comparison with wild type mice. Calvarial osteoblast
      cultures from five to eight days old Msx2 deficient, heterozygous and wild type
      mice were studied for difference in proliferation and differentiation.
      Proliferation rate was assessed by counting cell number, BrdU and Calcein AM
      labeling. Differentiation was assessed by Von Kossa and alkaline phosphatase
      staining, northern blot hybridization with bone differentiation markers,
      infection of cell cultures with retrovirus expressing GFP under the control of
      type I collagen promoter fragment. At day six, cell number in cell culture
      derived from Msx2 deficient mice was 20% lower then in culture from wild type
      mice. There were 16.8% BrdU labeled cells in cell culture from Msx2 deficient
      mice, 20.9% in culture from heterozygous mice and 21.6% in culture from wild type
      mice. Cell cultures from Msx2 deficient mice showed lower intensity of
      fluorescence when marked with Calcein AM then cultures from wild type mice. Von
      Kossa staining showed increased mineralization and northern blot analysis showed
      increased levels of bone differentiation markers in cell cultures derived from
      Msx2 deficient mice. GFP came on earlier in Msx2 deficient cultures after
      infection with Col2.3 GFP retrovirus. We conclude that calvarial osteoblasts
      derived from Msx2 deficient mice have a lower rate of proliferation and
      demonstrate increased osteoblastic differentiation when compared to osteoblasts
      derived from wild type mice.

PMID- 19860127
TI  - Comparison of digito-palmar dermatoglyphic traits in children with cerebral palsy
      and their close family members.
AB  - Cerebral palsy is one of the main causes of severe disability in children. Sixty
      children (30 boys and 30 girls) were included in the study. Quantitative digito
      palmar dermatoglyphic traits were analyzed. Prints of digito-palmar dermatoglyphs
      obtained from the children's parents (60 mothers and 60 fathers) and from 400
      phenotypically healthy adults from the Zagreb ware used as control groups.
      Analysis of quantitative dermatoglyphic traits of the digito-palmar complex
      revealed statistically significant differences in a number of variables between
      the fathers and their children suffering from cerebral palsy (TRC 180.3 > 158.6),
      with a greater number of variables involved in male children with cerebral palsy.
      Some variables showed statistically significant differences in dermatoglyphic
      patterns between fathers and control group of healthy males as well as between
      boys with cerebral palsy and healthy control males. Differences in dermatoglyphic
      patterns were significantly lower between mothers and girls with cerebral palsy
      (TRC 152.1 < 152.3) as well as between mothers and healthy control females. Study
      results support the hypothesis on the possible role of genetic predisposition in
      the occurrence of central nervous system lesion, with a more pronounced paternal
      impact.

PMID- 19860128
TI  - Interactions of MinK and e-NOS gene polymorphisms appear to be inconsistent
      predictors of atrial fibrillation propensity, but long alleles of ESR1 promoter
      TA repeat may be a promising marker.
AB  - Interactions of MinK and e-NOS Gene Polymorphisms Appear to Be Inconsistent
      Predictors of Atrial Fibrillation Propensity, but Long Alleles of ESR1 Promoter
      TA Repeat May Be a Promising Marker. We analyzed minK, e-NOS and ESR1 gene
      polymorphisms in 40 patients with atrial fibrillation (AF) without major
      structural heart disease compared to 35 healthy controls. A missense polymorphism
      in the minK gene with A/G substitution at nucleotide 112 causing serine (S) to
      glycine (G) change, 786 T/C polymorphism in the 5' flanking region of e-NOS gene
      and TA polymorphism in the regulatory region of estrogen receptor ESR1 gene with
      long (> or = 19 TA repeats) and short alleles were examined. Only a slight
      increase in minK G allele frequency, but with marked excess in AG/TT combination
      of minK and e-NOS polymorphisms was found in the AF group. The interpretation
      remains tentative due to small groups precluding statistical significance of
      differences, possible lab flaws and inconsistencies with earlier data. However,
      ESR1 long allele homozygotes were strikingly more frequent in the AF than in
      control group, reaching statistical significance surprisingly in males (p <
      0.02). Functional activity of estrogen receptors may be more critical in males
      than in females with abundance of circulating estrogen. Contrasting the intricate
      complexity of genetic polymorphisms influencing cardiac rhythm with our modest
      research, we would limit the conclusion to the plea for further research of ESR1
      role in AF.

PMID- 19860129
TI  - Occupational medicine in taking over work injuries from family practice--a one
      year follow-up.
AB  - Occupational medicine has taken over from Family practice the treatment of work
      injuries and occupational diseases in the Republic of Croatia since January 1,
      2008. The reason was too many long-lasting sick leaves which general
      practitioners were unable to curb adequately. The research objective was to show
      the results of the one-year follow-up of the carried out reform, i.e. the
      efficiency of Occupational medicine in the new function. The methods of data
      comparison and McNemar statistics were used of one-year follow-up in an
      Occupational medicine surgery that cares for 5800 employees in Littoral
      Mountainous County. From 32 patients in February 2008, 30 work injuries and 2
      occupational diseases, the overall number diminished in February 2009 to 13
      patients with work injuries and no diagnosed occupational disease, p < 0.001 for
      work injuries. Also the number of patients on sick leave over three months fell
      from 14 to 4. Occupational medicine has proved to be more efficient than Family
      practice in assessing sick leave. This does not mean that family practice, due to
      a number of reasons mentioned in the research, is of less importance. For the
      patient can always return to his general practitioner for further treatment, and
      sick leave if necessary, but not on the grounds of work injury and occupational
      disease.

PMID- 19860130
TI  - Ammonia intoxication on workplace--case report and a review of literature.
AB  - In December 2003 in Rijeka, Croatia, a work accident happened when in the meat
      industry 'Vir" a forklift damaged the ammonia pipe. Two butchers were acutely
      poisoned. The objective is to warn of the danger of ammonia and of the need to
      improve preventive programs of occupational medicine. The method of comparing the
      two injured workers, i.e. their spirometric values, was used. The results showed
      progressive diminishing of patients' respiratory abilities, in the patient with
      lungs transplanted VC 32%, FVC 33%, FEV1 16% and FEF75% = 6% in 2006, the year
      when he died. In the patient that survived, the values in 2008 were VC 43.5%, FVC
      27.2%, FEV1% 56.7% and FEF75% = 6%. The patients' CT showed diffused fibrosing
      and bronchiectasiae. Obliterating bronchiolitis developed in both patients. The
      second patient is the lung transplantation candidate. The first patient developed
      post transplantation cytomegalovirus pneumonia so he fought CMV antigenemia and
      infection till the end.

PMID- 19860131
TI  - Painless Acanthamoeba keratitis in a soft contact lens wearer--case report.
AB  - Aim of our paper is to present a case of painless Acanthamoeba keratitis in a
      soft contact lens wearer. A 17-year-old male, highly myopic, prolonged soft
      contact lens wearer, presented to us with painless red watery right eye having
      remarkably diminished vision. Last six weeks he was treated elsewhere for the
      microbial keratitis with no improvement. No pain was reported and on the direct
      questionnaire about it he denied it. There was marked mixed conjunctival and
      ciliary injection. A central stromal opacity with a pronounced surrounding
      corneal ring of inflammatory infiltration and epithelial defect was seen on
      biomicroscopy of the right eye. Circular pannus was already formed reaching
      epithelial defect overlying corneal ring infiltrate. Acanthamoeba spp in the
      corneal sample was confirmed. Prolonged therapy with 0.02% chlorhexidine
      digluconate solution combined with 0.1% hexamidine solution resulted in corneal
      healing left with a large central dense stromal opacity with circular pannus
      reaching peripheral third of the cornea but with very thin blood vessels and the
      best corrected visual acuity of 0.1 tested on Snellen chart. In conclusion, even
      in a lack of typical symptom for Acanthamoeba keratitis such as pain, this amoeba
      should be ruled out especially in a soft contact lens wearer.

PMID- 19860132
TI  - Keller's arthroplasty with proximal metatarsal opening wedge osteotomy in
      treating severe Hallux valgus deformity--surgical techniques and case report.
AB  - The paper presents an operative technique proposed for treating severe Hallux
      Valgus deformity with arthrosis of the first metatarsal joint in elderly people.
      The procedure consists of the Keller's arthroplasty in combination with basal
      osteotomy of the first metatarsal bone, whereby the head of the metatarsal is
      displaced laterally and plantarward. The osteotomy is fixed with a reconstructive
      plate. The results show a significant improvement in the hallux valgus angle, the
      first metatarsal angle, as well as in the plantar pressure distribution.

PMID- 19860133
TI  - "Alea Iacta Est" (a case series report of problem and pathological gambling).
AB  - Gambling or gaming is a common term for a group of various games, activities and
      behavior that involve wagering money on an event with an uncertain outcome with
      the primary intent of winning additional money, i.e., a player risks and hopes to
      get back what he/she had gambled, or to win more. When the player is unable to
      resist impulses to gamble, and gambling behavior harmfully affects him or the
      others, then he/she is suffering from the so called "pathological gambling",
      which is one of six categories of the "Impulse control disorders" in the
      International Classification of Diseases. Since, at present, there is no
      standardized program and approach to the problem of gambling in Croatia, and
      having in mind the arising accessibility and popularity of the "games of chance",
      the authors are presenting seven cases of problem and pathological gambling and
      call for broad public discussion on the problem from medical-psychiatric and
      forensic-point of view. The first patient was treated on an outpatient basis with
      cognitive-behavioral and family therapy for problem gambling; for the second
      patient was treated for impulse control disorders; for the third patient gambling
      was a symptom of psychotic form of depressive disorder; the fourth had primary
      diagnosis of personality disorder; and the fifth patient was prosecuted for armed
      robbery and evaluated by a psychiatric expert. The sixth and the seventh patients
      were women suffering from primary bipolar affective and major depressive
      disorder, respectively. The authors conclude that, due to the size of the problem
      and its consequences, the prevention of pathological gambling is very important.
      The prevention can be carried out primarily through screening at the school level
      and primary health care services, whereas secondary screening may be conducted
      through the system of psychiatric care. It is recommended to invest into
      research, education of a wider population, and development of preventive
      programs.

PMID- 19860134
TI  - After 40 years gossypiboma caused spleen abscess.
AB  - We report a case of spleen abscess cased by foreign body (gossypiboma) after 40
      years. After physical examination, laboratory, ultrasonography and CT findings
      with diagnosis of acute abdomen, 73 years old woman had undergone laparatomy.
      Operation revealed intraabdominal spleen abscess. Capsulotomy and drainage of the
      collection was performed before splenectomy. Histological examination showed
      foreign body material surrounded by chronic inflammation, foreign body-type
      multinucleated giant cells, extravasated red blood cells and fibroblastic
      proliferation. From anamnesis we found that woman was operated only once during a
      life with diagnosis of extrauterine pregnancy, 40 years ago. Spleen abscess
      caused by gossypiboma after 40 years was never described before. However,
      diagnosis like this is very well known but rarely published because medical-legal
      implication. Education, professionalism and cooperation of all persons involved
      in surgical procedure are very important to prevent accidentally mistakes.

PMID- 19860135
TI  - Women and stroke: how much do women and men differ? A review--diagnostics,
      clinical differences, therapy and outcome.
AB  - In this article, the authors have gathered data from epidemiological,
      observational, case-control and cohort studies to evaluate the differences
      between men and women in terms of ischemic events, mainly stroke. The authors are
      highlighting the differences that exist between men and women and play a role in
      terms of social diversities, and the pathophysiological differences that may be
      responsible at least in part for ischemic events. Studies show that male stroke
      patients are more likely to have a history of ischemic heart disease, smoking and
      alcohol consumption, whereas female stroke patients suffer from ischemic events
      at an older age, are more likely to have hypertension and atrial fibrillation.
      Women are more likely to arrive to an emergency room in a comatose state, with
      paralysis, aphasia, swallowing problems and urinary incontinence, which all
      indicates a more severe stroke. Also, women suffer from a higher level of
      disability than men, even though their survival rates are the same. Even though
      clear guidelines for the treatment of stroke exist, there are still differences
      in both diagnostic procedures and discharge destination between male and female
      patients.

PMID- 19860136
TI  - Hyperbaric oxygen improves nasal air flow.
AB  - OBJECTIVE: We investigated whether hyperbaric oxygen (HBO2) treatment is able to
      cause any changes in the nasal peak inspiratory flow (NPIF) values of patients
      submitted to this therapy. STUDY DESIGN: NPIF was measured in a group of 13
      patients who were submitted to at least 10 sessions of 75 minutes long HBO2
      treatments over a period of 20 days. HBO2 was prescribed to the patients to treat
      hearing loss, diabetic ulcers or chronic inflammatory disease. Three timings were
      chosen to perform the NPIF measurements: during HBO2, five minutes before and
      five minutes after the treatment. METHODS: For NPIF evaluation, the highest
      inspiratory flow of three inspirations was recorded. To search for statistical
      differences between NPIF measurements at the three different timings of the HBO2
      treatment, we have analysed the data using the repeated measures ANOVA test with
      the Epsilon lower bound correction for the F ratio. RESULTS: NPIF values were
      significantly higher when the patients were inside the HBO2 chamber when compared
      with NPIF measurements obtained in the same individuals five minutes before
      starting or five minutes after ending the treatment. A small but significant
      increase in NPIF values was detected in patients five minutes after stopping the
      HBO2 treatment, in comparison with values obtained five minutes before initiating
      the therapy. NPIF values remained stable along the 10 HBO2 sessions, i.e. with
      repetition of the HBO2 treatments, NPIF values were not further enhanced.
      CONCLUSIONS: Exposure to HBO2 causes significant improvement in nasal air flow.
      This increase is restricted mostly to the period that the patients are inside the
      hyperbaric chamber. Further investigations are needed to determine the relative
      contributions of enhancement in air pressure and in oxygen concentration (that
      characterize HBO2) in the enhancement of nasal air flow. The herein finding may
      be helpful in future investigations on the treatment of nasal or sinus diseases.

PMID- 19860137
TI  - Dual effects of hyperbaric oxygen on proliferation and cytotoxic T lymphocyte
      activity of rat splenic lymphocytes.
AB  - Contradictory reports exist regarding the effects of hyperbaric oxygen (HBO2) on
      immune functions. We hypothesized that the intensity of exposure is a key factor,
      which leads to the different effects of HBO2 on immunity. In this study, we
      determined the function of rat splenic lymphocytes after in vitro exposure to
      different pressure-durations of HBO2. The proliferation rate and total cytotoxic
      T lymphocyte (CTL) activity stimulated by concanavalin A were enhanced by
      exposure to low (100 kPa for 60 or 90 minutes and 150 kPa for 30 or 60 minutes)
      HBO2 pressure-durations, but were inhibited by exposure to higher pressure
      durations. We conclude that HBO2 exerts dual effects on lymphocyte function, as
      appropriate exposure promotes and excessive exposure inhibits the functions.

PMID- 19860138
TI  - Monthly variations in the diagnosis of carbon monoxide exposures in the emergency
      department.
AB  - INTRODUCTION: Carbon monoxide (CO) poisoning is the leading cause of
      toxicological deaths worldwide. Symptoms may be subtle, contributing to its
      frequent delay in diagnosis. If a seasonal variation occurs, a heightened
      awareness during peak time may lead to improved recognition and diagnosis. STUDY
      OBJECTIVES: To determine whether monthly variations in CO poisoning occur in
      emergency departments. METHODS:  DESIGN: A multicenter retrospective emergency
      department (ED) cohort. STUDY SETTING: 23 New Jersey and New York emergency
      departments. SUBJECTS: Consecutive patients with the ICD-9 primary diagnosis
      of"toxic effects CO" from January 1, 2000 to October 31, 2006. STATISTICS: We
      tested for significant differences using chi-square and Student's t-test with
      alpha set at 0.5. RESULTS: There were 1,006 patients who were diagnosed in the ED
      with CO toxicity (0.024% of all ED patients). Mean age was 30 years (SD +/- 20),
      54% were female, and Caucasians compromised 54% of participants. Thirty-nine
      percent of documented patients arrived via ambulance and 90% were subsequently
      discharged. Incidence of CO visits peaked in December (0.036%) and were least
      likely in May (0.011%). Mean monthly CO visits were statistically increased
      during October (p = < 0.0001), November (p = 0.008), December (< 0.0001), January
      (p = 0.01), and March (p = 0.04). Statistically fewer case of CO exposure were
      diagnosed in May (p = 0.0003), June (p = 0.005), August (p = < 0.0001), and
      September (p = 0.002).

PMID- 19860139
TI  - Retinal angiography: noninvasive, real-time bubble assessment from the ocular
      fundus.
AB  - Formation of bubbles in tissue and vasculature from a sudden reduction in ambient
      pressure is likely an underlying cause of the clinical symptoms of decompression
      sickness (DCS). Thus, tools detecting bubbles in the vasculature may be important
      for evaluating DCS. Sheep were air-compressed to 6.0 ATA (30 minutes bottom time)
      then rapidly decompressed to the surface. A fundus camera was quickly positioned
      for continuous observation of the retinal vasculature. Bubbles were observed in
      the retinal vasculature of 25.8% (n = 31) of the sheep. Bubble onset time ranged
      from 5-22 minutes post-chamber and lodge time ranged from 0-70+ minutes. Bubbles
      were visualized mostly in the arteries of the retinal circulation. Severe
      vasoconstriction was captured using red-free angiography in two sheep. In two
      other sheep, fluorescein angiography demonstrated occluded blood flow caused by
      arterial gas emboli. This study demonstrates that retinal angiography is a
      practical tool for real-time, noninvasive detection of bubbles in the retinal
      circulation, a visible window to the cerebral circulation. Thus retinal
      angiography may prove invaluable in the early detection of arterial gas emboli in
      the cerebral circulation, the resolution of which is imperative to favorable
      neurological outcomes. This study also presents for the first time images of
      bubbles in the retinal circulation associated with DCS captured by a fundus
      camera.

PMID- 19860140
TI  - Kinetics and thermodynamics of arsenate and arsenite biosorption by pretreated
      spent grains.
AB  - Using chemically modified spent grains as a new biosorbent to treat arsenate and
      arsenite ions was studied. The influences of pH, contact time, initial
      concentration and temperature were studied in batch experiments. The equilibrium
      process was described well by Langmuir isotherm model with maximum biosorption
      capacities of 13.39 and 4.86 mg/g of arsenate and arsenite on spent grains,
      respectively. The initial removal was rapid, and equilibrium was established in
      less than 180 min. Good correlation coefficients were obtained for the pseudo
      second-order kinetic model. In the binary metal solutions, the finite sites on
      the surface of spent grains showed a greater preference for As(V) ions. The
      enthalpy of biosorption was exothermic and the increase in As(III) removal was
      larger than that of As(V) over the same rise in temperature. In this study, spent
      grains proved to be suitable for removal of As(V) and As(III) from the effluent
      of metallurgical industry.

PMID- 19860141
TI  - Enhancement of sludge settling with chemical additives.
AB  - Solids in aeration tank effluents contribute to the total organic content and
      suspended solids concentration, and violates disposal and reuse standards.
      Therefore, improving the settling properties of sludge helps produce an effluent
      with a quality that conforms to effluent standards, assuming all other conditions
      for good settling in the sedimentation tank are favorable. In this paper, seven
      chemicals that are all cationic polyelectrolytes were tested individually as
      additives to improve the settling properties of aeration tank effluent from a
      full-scale wastewater treatment plant. Pilot settling columns designed and
      constructed at a local wastewater treatment plant were used in this project.
      Batch settling tests were performed on fresh activated sludge samples that were
      collected before the secondary sedimentation tank and mixed with different
      concentrations of the additives without cumulative additions. Each additive was
      accessed based on its particular sludge settling properties, that is, the shape
      of the settling curves, the values of the hindered zone settling rate or zone
      settling velocity, and the stirred sludge volume index. Each additive result was
      compared with the corresponding properties of a plain sludge sample collected on
      the same day and used as a control. Substantial and dissimilar improvements were
      obtained and are presented in the form of graphs and values using 92 settling
      runs. Shorter lag-times, quicker descending speed of sludge-water interface,
      higher descending distance, and lower stirred sludge volume indices values were
      attained with the use of these additives.

PMID- 19860142
TI  - Updated activated sludge model number 1 parameter values for improved prediction
      of nitrogen removal in activated sludge processes: validation at 13 full-scale
      plants.
AB  - The Activated Sludge Model number 1 (ASM1) is the main model used in simulation
      projects focusing on nitrogen removal. Recent laboratory-scale studies have found
      that the default values given 20 years ago for the decay rate of nitrifiers and
      for the heterotrophic biomass yield in anoxic conditions were inadequate. To
      verify the relevance of the revised parameter values at full scale, a series of
      simulations were carried out with ASM1 using the original and updated set of
      parameters at 20 degrees C and 10 degrees C. The simulation results were compared
      with data collected at 13 full-scale nitrifying-denitrifying municipal treatment
      plants. This work shows that simulations using the original ASM1 default
      parameters tend to overpredict the nitrification rate and underpredict the
      denitrification rate. The updated set of parameters allows more realistic
      predictions over a wide range of operating conditions.

PMID- 19860143
TI  - Bioaerosol in composting facilities: occupational health risk assessment.
AB  - This research found evidence of an association between occupational exposure to
      bioaerosols in composting plants and health outcome occurrence in exposed
      workers. An occupational exposure assessment in six composting plants was
      performed to better characterize personal exposure levels and evaluate associated
      health risk in workers. Sampling results showed large ranges of concentrations of
      dust, bacteria, molds, and endotoxin in ambient air and in personal samples, both
      when driving a front-end loader and when cleaning, monitoring, and performing
      maintenance tasks. Mean personal exposure levels were high at 100 to more than
      10,000 times higher than outdoor background levels and fully consistent with
      occurrence of inflammatory and allergic respiratory outcomes among workers.
      Engineering control, personal protection, and education and training programs for
      employees, health, and safety officials, and occupational physicians are being
      developed and implemented.

PMID- 19860144
TI  - Changes in antibiotic resistance patterns of Escherichia coli during domestic
      wastewater treatment.
AB  - Changes in antibiotic resistance of Escherichia coli in the different stages of
      conventional domestic wastewater treatment were investigated. Over two years,
      more than 3500 E. coli isolates from four stages of the wastewater treatment
      process were tested for resistance to six different antibiotics. The percent
      resistance of bacteria from any of the stages was highly variable in different
      samples. Because of this variability, no statistically significant difference was
      found in the overall percent resistance of E. coli from influent to effluent.
      When comparing different stages within samples, however, there seemed to be an
      increase in resistance to ampicillin and amoxicillin between the raw influent and
      primary effluent. In addition, the percent of isolates with multiple antibiotic
      resistance, resistant to more than one and less than five antibiotics, and highly
      multiple antibiotic resistance, resistant to at least five antibiotics, increased
      through the treatment process.

PMID- 19860145
TI  - Importance of particulate biodegradable organic compounds in performance of full
      scale biological phosphorus removal system.
AB  - In this study, biological treatment performances of two parallel treatment lines
      operating with and without primary sedimentation were investigated. The research
      was carried out in a large-scale enhanced biological phosphorus removal (EBPR)
      process. Influent and effluent of treatment lines were characterized continuously
      during the study. In addition, anaerobic anoxic and aerobic EBPR activities were
      investigated by batch tests using fresh activated sludge samples. All of the
      environmental and operational conditions of the treatment lines were
      statistically compared. Evaluation of effluent compositions indicated that EBPR
      performances of treatment lines were significantly different. Results of the
      research also indicated that settling characteristics of the activated sludge
      process could be improved significantly with increasing particulate biodegradable
      organic compound (pbCOD) loading rate. Batch test results revealed that
      anaerobic, anoxic, and aerobic biochemical reaction rates of activated sludge
      cultivated on increased pbCOD loading rate were significantly higher compared to
      activated sludge cultivated on soluble substrate forms.

PMID- 19860146
TI  - Comparison of the effects of conventional and alternative external carbon sources
      on enhancing the denitrification process.
AB  - Food industry effluents are considered a potential alternative for methanol when
      seeking external carbon sources to enhance denitrification in municipal
      wastewater treatment plants (WWTPs). The aim of this study was to determine the
      immediate effects of dosing different carbon sources on the denitrification
      capability of process biomass from the Wschod WWTP in Gdansk (northern Poland).
      Five carbon sources, including settled wastewater, methanol, and three industrial
      effluents (distillery, brewery, and fish-pickling process) were tested in two
      kinds of batch experiments. The acclimation period of biomass to methanol also
      was investigated in bench-scale systems. During the conventional batch
      experiments, with the industrial effluents, the observed nitrate utilization
      rates (NURs) ranged from 2.4 to 6.0 g N/(kg VSS x h), which were only slightly
      lower than the rates associated with the use of the readily biodegradable
      fraction in the municipal (settled) wastewater [4.6 to 7.8 g N/(kg VSS x h)]. The
      conventional NURs observed with methanol and non-acclimated process biomass were
      low [i.e., 0.4 to 1.5 g N/(kg VSS x h)], and a minimum 2-week acclimation period
      of biomass to methanol in the bench-scale systems was needed to reach the level
      of 4.0 g N/(kg VSS x h). In other experiments, dosing the distillery and fish
      pickling effluents at the beginning of the anoxic phase (preceded by the
      anaerobic phase) resulted in considerably higher (over 20%) NURs compared with
      the same experiments with the other carbon sources.

PMID- 19860147
TI  - Effects of fluctuating iron dosage on nitrification in integrated fixed film and
      conventional activated sludge processes.
AB  - An integrated fixed-film activated sludge (IFFAS) process with four media cells
      is operating in parallel with a conventional activated sludge (CAS) train at
      Lakeview Wastewater Treatment Plant (Ontario, Canada). During winter 2007, an
      intensive sampling campaign was conducted to monitor the temporal and spatial
      variations of the nitrification capacity within the two plug-flow reactors. At
      the beginning of the six-week study, the CAS train was partially nitrifying,
      whereas the IFFAS train was nitrifying completely using the first two IFFAS cells
      only. Within one week, the CAS train lost nitrification because of a drop in
      solids retention time and pH caused by the onset of iron overdosing. When the
      IFFAS train received an iron spike, the carriers at the injection point (first
      cell) became iron-coated and lost 80% of their nitrification capacity. However,
      this train maintained its total nitrification capacity using the reserve capacity
      in the three remaining cells.

PMID- 19860148
TI  - Anaerobic membrane bioreactor treatment of synthetic municipal wastewater at
      ambient temperature.
AB  - The performance of a crossflow anaerobic membrane bioreactor (AnMBR) to treat
      synthetic municipal wastewater was investigated at different hydraulic retention
      times (HRTs). The AnMBR was operated at chemical oxygen demand (COD) loading
      rates of 1 to 2 kg COD/m3 x d for 280 days. The permeate COD concentration was
      always lower than 40 mg/L, and no noticeable volatile fatty acids were detected,
      regardless of HRT variations, while soluble COD (SCOD) was accumulated in the
      reactor with decreases in HRT. The particle size reduction was relatively lower
      than other studies reported, even after a long operation time resulting from the
      low operation crossflow velocity. Approximately 30% of COD was not available for
      methane recovery, irrespective of applied HRTs, as a result of the COD loss by
      dissolved methane, sulfate reduction, and untreated COD in the permeate. The
      fraction of methane recovered from the synthetic municipal wastewater decreased
      from 48 to 35%, with the decrease of HRT from 12 to 6 hours, as a result of the
      increase of mixed-liquor SCOD, which was rejected and accumulated in the AnMBR.
      Therefore, AnMBR operation with relatively long HRTs and SRTs may be favorable,
      to enhance methane recovery and reduce or eliminate sludge production.

PMID- 19860149
TI  - Quantification of thermotolerant Campylobacter in Swiss water treatment plants,
      by real-time quantitative polymerase chain reaction.
AB  - A total of 49 wastewater samples from 23 different wastewater treatment plants
      (WWTPs) were analyzed using real-time quantitative polymerase chain reaction for
      the presence and quantity of thermotolerant campylobacters. Thermotolerant
      campylobacters were detected in 87.5% (21/24) and 64% (16/25) of untreated and
      treated wastewater samples, respectively. Their concentration was sufficiently
      high to be quantified in 20.4% (10/49) of the samples. In these samples, the
      concentration ranged from 68,000 to 2,292,000 cells/L in untreated wastewater and
      from 10,800 to 28,000 cells/L in treated water. We conclude that thermotolerant
      campylobacters present a health hazard for workers at WWTPs in Switzerland.

PMID- 19860150
TI  - Of: Effects of suburban land use on phosphorus fractions and speciation in the
      Upper Peruque Creek, Eastern Missouri, S. Keller, T. Q. Zhang, S. Webb, R.
      Brugam, K. Johnson, Z.-Q. Lin, 80, 316-323 (2008).

PMID- 19860151
TI  - United National climate conference, COP15.

PMID- 19860152
TI  - Fishing for feed or fishing for food: increasing global competition for small
      pelagic forage fish.
AB  - At present, small pelagic forage fish species (includes anchovies, herring,
      mackerel, sardines, etc.) represent the largest landed species group in capture
      fisheries (27.3 million t or 29.7% of total capture fisheries landings in 2006).
      They also currently constitute the major species group actively fished and
      targeted for nonfood uses, including reduction into fishmeal and fish oil for use
      within compound animal feeds, or for direct animal feeding; the aquaculture
      sector alone consumed the equivalent of about 23.8 million t of fish (live weight
      equivalent) or 87% in the form of feed inputs in 2006. This article attempts to
      make a global analysis of the competition for small pelagic forage fish for
      direct human consumption and nonfood uses, particularly concerning the important
      and growing role played by small pelagic forage fish in the diet and food
      security of the poor and needy, especially within the developing countries of
      Africa and the Sub-Saharan region.

PMID- 19860153
TI  - Coastal eutrophication thresholds: a matter of sediment microbial processes.
AB  - In marine sediments, the major anaerobic mineralization processes are Fe(III)
      oxide reduction and sulfate reduction. In this article, we propose that the two
      alternative microbial mineralization pathways in sediments exert decisively
      different impacts on aquatic ecosystems. In systems where iron reduction
      dominates in the recently deposited sediment layers, the fraction of Fe(III)
      oxides that is dissolved to Fe(II) upon reduction will ultimately be transported
      to the oxic layer, where it will be reoxidized. Phosphorus, which is released
      from Fe(III) oxides and decomposing organic matter from the sediment, will be
      largely trapped by this newly formed Fe(III) oxide layer. Consequently, there are
      low concentrations of phosphorus in near-bottom and productive water layers and
      primary production tends to be limited by phosphorus (State 1). By contrast, in
      systems where sulfate reduction dominates, Fe(III) oxides are reduced by
      sulfides. This chemical reduction leads to the formation and permanent burial of
      iron as solid iron sulfides that are unable to capture phosphorus. In addition,
      the cycling of iron is blocked, and phosphorus is released to overlying water.
      Owing to the enrichment of phosphorus in water, the nitrogen : phosphorus ratio
      is lowered and nitrogen tends to limit algal growth, giving an advantage to
      nitrogen-fixing blue-green algae (State 2). A major factor causing a shift from
      State 1 to State 2 is an increase in the flux of labile organic carbon to the
      bottom sediments; upon accelerating eutrophication a critical point will be
      reached when the availability of Fe(III) oxides in sediments will be exhausted
      and sulfate reduction will become dominant. Because the reserves of Fe(III)
      oxides are replenished only slowly, reversal to State 1 may markedly exceed the
      time needed to reduce the flux of organic carbon to the sediment. A key factor
      affecting the sensitivity of a coastal system to such a regime shift is formed by
      the hydrodynamic alterations that decrease the transport of O2 to the near-bottom
      water, e.g., due to variations in salinity and temperature stratification.

PMID- 19860154
TI  - Forest management and biodiversity conservation based on natural ecosystem
      dynamics in northern Europe: the complexity challenge.
AB  - Recent research in northern Europe has revised many long-held conceptions of the
      complexity of forest ecosystems and their natural structure and dynamics. The
      unveiling of the picture of natural characteristics of forest ecosystem structure
      and dynamics reveals much more diversity than its traditional complement,
      highlighting the importance of non-stand-replacing disturbances and the
      associated heterogeneous and dynamic stand and landscape structures. This
      increasing detail is a reflection of a fundamental change in the ecological
      understanding of forests as complex ecosystems. In particular, the generalization
      that the boreal forest is regulated by fierce stand-replacing disturbances,
      leading to the dominance of even-aged stand successions, has been disproved.
      However, this misconception has, until now, been repeated and used to legitimize
      the dominant practice of clear-cutting as a nature-based way to manage the
      forest. The practical conclusion of this review paper is that the dominating
      forest management model in North European boreal forests, which is based on the
      clear-cut harvesting of timber and growing of even-aged stands, is in
      contradiction with the variable and complex characteristics of the disturbance
      succession cycle observed in naturally dynamic forests with negligible human
      impact. As a consequence, the structural variation of the boreal forest under
      management has been grossly truncated compared with its natural range. Because of
      this, and due to the scarcity of protection areas in many regions of northern
      Europe, it is not likely that the conservation of native biodiversity and
      ecological sustainability will be attained, assuming that the model of forest
      management remains unchanged. Thus, there is a strong incentive for change in the
      prevailing forest management model toward one that is based on natural ecosystem
      dynamics and an understanding of forests as complex systems.

PMID- 19860155
TI  - Estimating net primary production of Swedish forest landscapes by combining
      mechanistic modeling and remote sensing.
AB  - The aim of this study was to investigate a combination of satellite images of
      leaf area index (LAI) with process-based vegetation modeling for the accurate
      assessment of the carbon balances of Swedish forest ecosystems at the scale of a
      landscape. Monthly climatologic data were used as inputs in a dynamic vegetation
      model, the Lund Potsdam Jena-General Ecosystem Simulator. Model estimates of net
      primary production (NPP) and the fraction of absorbed photosynthetic active
      radiation were constrained by combining them with satellite-based LAI images
      using a general light use efficiency (LUE) model and the Beer-Lambert law. LAI
      estimates were compared with satellite-extrapolated field estimates of LAI, and
      the results were generally acceptable. NPP estimates directly from the dynamic
      vegetation model and estimates obtained by combining the model estimates with
      remote sensing information were, on average, well simulated but too homogeneous
      among vegetation types when compared with field estimates using forest inventory
      data.

PMID- 19860156
TI  - Reforesting "bare hills" in Vietnam: social and environmental consequences of the
      5 million hectare reforestation program.
AB  - In recent years, forestry has been strongly promoted by the government of the
      Socialist Republic of Vietnam through large-scale projects to rehabilitate and
      reforest millions of hectares of land. One project to reforest 5 million hectares
      has received hundreds of millions of US dollars for implementation. Yet based on
      a case study in one area of northern Vietnam, this project appears to have had a
      number of unforeseen consequences. Large areas of land classified as "bare hills"
      have been targeted for reforestation, despite the fact that these lands already
      harbor a number of species that were used by local communities. The bare hills
      were especially economically important to poor households and to women who
      collected a variety of nontimber forest products there. Because the reforestation
      project focused most efforts on establishing new plantations rather than
      supporting natural regeneration, diverse sources of non-timber forest products
      were being replaced with monocrop exotic tree plantations. A strong inequity in
      the allocation of private lands for reforestation has characterized the
      regreening projects to date, and this may have continuing unwelcome social,
      environmental, and economic impacts into the future, particularly for the poor.

PMID- 19860157
TI  - Zinc in soils, crops, and meals in the Niger Inland Delta, Mali.
AB  - Zinc deficiency is a problem in developing countries and not least so in Africa.
      This concerns both agriculture and human food provision. Zinc deficiency in soils
      may severely decrease yields, whereas insufficient zinc in food intake primarily
      affects the immune defense, notably in children. The present investigation
      concerned zinc availability in soils, crops, and food in the Niger inland delta
      in Mali. Agricultural soils are largely deficient in plant-available zinc,
      however, soils in close vicinity to habitation show elevated zinc concentrations.
      The zinc concentrations in crops are low; in rice, they are about half of
      reference ranges. Zinc intake assessed from a number of sampled meals was about
      half the recommended requirement. When zinc concentration is higher phytate was
      also high, which made the zinc less available. In spite of a recorded sufficient
      intake of iron, anemia is common and is most likely because of the high phytate
      concentration in the cereal-dominated diet. Increasing zinc and iron availability
      would be possible through the use of malting, fermentation, and soaking in food
      preparation. Finally, in the long run, any trace element deficiency, especially
      that of zinc in agricultural soils needs to be amended by addition of appropriate
      amounts in commercial fertilizers.

PMID- 19860158
TI  - Environmental harm of hidden subsidies: global warming and acidification.
AB  - We investigate environmental impacts of off-budget or indirect subsidies, which,
      unlike on-budget subsidies, are not visible in government budgets. Such subsidies
      have received little attention in economic and environmental research, even
      though they may be at least as important from an environmental perspective as on
      budget subsidies. We offer a typology of indirect subsidies. Next, we estimate
      the magnitude of these subsidies and their impact on greenhouse gas (GHG) and
      acidifying emissions for the agriculture, energy, and transport sectors in The
      Netherlands. The calculations are based on a model approach that translates a
      particular subsidy into price and quantity changes using empirical elasticities,
      followed by environmental effect estimates using pollution-intensity parameters.
      The various environmental pollution effects are aggregated into environmental
      indicators. The results show, among others, that GHG emissions caused by off
      budget subsidies contribute to more than 30% of the policy targets specified by
      the Kyoto Protocol for CO2 emissions reduction by The Netherlands. Reforming or
      removing off-budget subsidies may thus be an important strategy of effective
      climate policy.

PMID- 19860159
TI  - Plastic responses to different habitat type contribute to Hyptis suaveolens Poit.
      invasiveness in the dry deciduous forest of India.

PMID- 19860160
TI  - US Airways Flight 1549 Hudson river crash: the New Jersey experience.
AB  - The authors review the preparation, implementation, and management of the US
      Airways Flight 1549 Hudson River crash. This is a review of the experience of NJ.
      The state planning that created the ability to execute the treatment of patients
      from time of impact in the river until debriefing is reviewed.

PMID- 19860161
TI  - An algorithm for the evaluation and management of red, yellow, and green zone
      patients during a botulism mass casualty incident.
AB  - Botulinum toxin is one of the most toxic substances known to humankind. It is one
      among the six Category A agents in the CDC bioterrorism lexicon. This suggests
      that, while the possibility of a botulism mass casualty incident (MCI) is remote,
      its unique acute and long-term ramifications must be addressed and planned for.
      However, an in-depth knowledge of the disease and its tactical management in the
      acute MCI phase is inconsistent or superficial among healthcare personnel.
      Therefore, an algorithm has been developed to assist first receivers with the
      initial management of multiple probable and potential botulism patients when
      equipment resources are strained and when expert personnel are not readily
      available. The algorithm is specifically structured to assist with the
      identification and management of potential respiratory deterioration of suspected
      botulism patients.

PMID- 19860162
TI  - Pandemic influenza and major disease outbreak preparedness in US emergency
      departments: a survey of medical directors and department chairs.
AB  - STUDY OBJECTIVES: To quantify the readiness of individual academic emergency
      departments (EDs) in the United States for an outbreak of pandemic influenza.
      METHODS, DESIGN, AND SETTING: Cross-sectional assessment of influenza pandemic
      preparedness level of EDs in the United States via survey of medical directors
      and department chairs from the 135 academic emergency medicine departments in the
      United States. Preparedness assessed using a novel score of 15 critical
      preparedness indicators. Data analysis consisted of summary statistics, chi2, and
      ANOVA. PARTICIPANTS: ED medical directors and department chairs. RESULTS: One
      hundred and thirty academic emergency medicine departments contacted; 66 (50.4
      percent) responded. Approximately half (56.0 percent) stated their ED had a
      written plan for pandemic influenza response. Mean preparedness score was 7.2 (SD
      = 4.0) out of 15 (48.0 percent); only one program (1.5 percent) achieved a
      perfect score. Respondents from programs with larger EDs (= 30 beds) were more
      likely to have a higher preparedness score (p < 0.035), an ED pandemic
      preparedness plan (p = 0.004) and a hospital pandemic preparedness plan (p =
      0.007). Respondents from programs with larger EDs were more likely to feel that
      their ED was prepared for a pandemic or other major disease outbreak (p = 0.01).
      Only one-third (34.0 percent) felt their ED was prepared for a major disease
      outbreak, and only 27 percent felt their hospital was prepared to respond to a
      major disease outbreak. CONCLUSIONS: Significant deficits in preparedness for
      pandemic influenza and other disease outbreaks exist in US EDs, relative to HHS
      guidelines, which appear to be related in part to ED size. Further study should
      be undertaken to determine the barriers to appropriate pandemic preparedness, as
      well as to develop and validate preparedness metrics.

PMID- 19860163
TI  - Investment, managerial capacity, and bias in public health preparedness.
AB  - OBJECTIVE: Nearly $7 billion has been invested through national cooperative
      funding since 2002 to strengthen state and local response capacity. Yet, very
      little outcome evidence exists to analyze funding effectiveness. The objective of
      this research is to analyze the relationship between investment (funding) and
      capacity (readiness) for public health preparedness (PHP). The aim of the authors
      is to use a management framework to evaluate capacity, and to explore the
      "immediacy bias" impact on investment stability. DESIGN: This study employs a
      longitudinal study design, incorporating survey research of the entire population
      of 68 health departments in the state of Texas. METHODS: The authors assessed the
      investment-capacity relationship through several statistical methods. The authors
      created a structural measure of managerial capacity through principal components
      analysis, factorizing 10 independent variables and augment this with a perceived
      readiness level reported from PHP managers. The authors then employ analysis of
      variance, correlation analyses, and other descriptive statistics. RESULTS: There
      has been a 539 percent coefficient of variation in funding at the local level
      between the years 2004 and 2008, and a 63 percent reduction in total resources
      since the peak of funding, using paired sample data. Results suggest that
      investment is positively associated with readiness and managerial capacity in
      local health departments. The authors also find that investment was related to
      greater community collaboration, higher adoption of Incident Command System (ICS)
      structure, and more frequent operational drills and exercises. CONCLUSIONS:
      Greater investment is associated with higher levels of capacity and readiness.
      The authors conclude from this that investment should be stabilized and
      continued, and not be influenced by historical cognitive biases.

PMID- 19860164
TI  - Public health preparedness for the impact of global warming on human health.
AB  - OBJECTIVE: To assess the changes in weather and weather-associated disturbances
      related to global warming; the impact on human health of these changes; and the
      public health preparedness mandated by this impact. DESIGN: Qualitative review of
      the literature. Articles will be obtained by searching PubMed database, Google,
      and Google Scholar search engines using terms such as "global warming," "climate
      change," "human health," "public health," and "preparedness." RESULTS: Sixty
      seven journal articles were reviewed. CONCLUSIONS: The projections and signs of
      global environmental changes are worrisome, and there are reasons to believe that
      related information may have been conservatively interpreted and presented in the
      recent past. Although the challenges are great, there are many opportunities for
      devising beneficial solutions at individual, community, and global levels. It is
      essential for public health professionals to become involved in advocating for
      change at all of these levels, as well as through professional organizations. We
      must begin "greening" our own lives and clinical practice, and start talking
      about these issues with patients. As we build walkable neighborhoods, change
      methods of energy production, and make water use and food production and
      distribution more sustainable, the benefits to improved air quality, a stabilized
      climate, social support, and individual and community health will be dramatic.

PMID- 19860165
TI  - A state survey of emergency department preparedness for the care of children in a
      mass casualty event.
AB  - OBJECTIVE: The Institute of Medicine has issued two reports over the past 10
      years raising concerns about the care of children in the emergency medical care
      system of the United States. Given that children are involved in most mass
      casualty events and there are deficiencies in the day-to-day emergency care of
      children, this project was undertaken to document the preparedness of hospitals
      in AR for the care of children in mass casualty or disaster situations. DESIGN:
      Mailed survey to all emergency department medical directors in AR. Nonresponders
      received a second mailed survey and an attempt at survey via phone. PARTICIPANTS:
      Medical directors of the emergency departments of the 80 acute care hospitals in
      AR. RESULTS: Seventy-two of 80 directors responded (90 percent response rate).
      Only 13 percent of hospitals reported they have pediatric mass casualty protocols
      and in only 28 percent of hospitals the disaster plan includes pediatric-specific
      issues such as parental reunification. Most hospitals hold mass casualty training
      events (94 percent), at least annually, but only 64 percent report including
      pediatric patients in their disaster drills. Most hospitals include local fire
      (90 percent), police (82 percent), and emergency medical services (77 percent) in
      their drills, but only 23 percent report involving local schools in the disaster
      planning process. Eighty-three percent of hospitals responding reported their
      staff is trained in decontamination procedures. Thirty-five percent reported
      having warm water showers available for infant/children decontamination. Ninety
      four percent of hospitals have a plan for calling in extra staff in a disaster
      situation, which most commonly involves a phone tree (43 percent). Ninety-three
      percent reported the availability of Ham Radios, walkie-talkie, or Arkansas
      Wireless Information Network (AWIN) units for communication in case of land line
      loss, but only 16 percent reported satellite phone or Tandberg units. Twelve
      percent reported reliance on cell phones in this situation. CONCLUSIONS: This
      survey demonstrated important deficiencies in the preparedness of hospitals in AR
      for the care of children in disaster. Although many hospitals are relatively well
      prepared for the care of adults in disaster situations, the needs of children are
      different and hospitals in AR are not as well prepared for pediatric disaster
      care.

PMID- 19860166
TI  - Terrorist suicide bombings: lessons learned in Metropolitan Haifa from September
      2000 to January 2006.
AB  - BACKGROUND: The threat of suicide bombing attacks has become a worldwide problem.
      This special type of multiple casualty incidents (MCI) seriously challenges the
      most experienced medical facilities. METHODS: The authors concluded a
      retrospective analysis of the medical management of victims from the six suicide
      bombing attacks that occurred in Metropolitan Haifa from 2000 to 2006. RESULTS:
      The six terrorist suicide bombing attacks resulted in 411 victims with 69 dead
      (16.8 percent) and 342 injured. Of the 342 injured, there were 31 (9.1 percent)
      severely injured, seven (2.4 percent) moderately severely injured, and 304 (88.9
      percent) mildly injured patients. Twenty four (77 percent) of the 31 severely
      injured victims were evacuated to the level I trauma center at Rambam Medical
      Center (RMC). Of the seven severely injured victims who were evacuated to the
      level II trauma centers (Bnai-Zion Medical Center and Carmel Medical Center)
      because of proximity to the detonation site, three were secondarily transferred
      to RMC after initial resuscitation. Eight of the 24 severely injured casualties,
      admitted to RMC, eventually died of their wounds. There was no in-hospital
      mortality in the level II trauma centers. CONCLUSIONS: A predetermined
      metropolitan triage system which directs trauma victims of a MCI to the
      appropriate medical center and prevents overcrowding of the level I facility with
      less severe injured patients will assure that critically injured patients of a
      suicide bombing attack will receive a level of care that is comparable with the
      care given to similar patients under normal circumstances. Severe blast injury
      victims without penetrating injuries but with significant pulmonary damage can be
      effectively managed in ICUs of level II trauma centers.

PMID- 19860167
TI  - [Rehabilitation management in private insurance].

PMID- 19860168
TI  - [Recommendations for independent medical examinations of PTSD claimants].
AB  - In Germany, like in many Western countries, posttraumatic stress disorder (PTSD)
      is being diagnosed on an increased scale; it has become a major cost-producing
      factor of the healthcare and insurance industry. However, diagnosing PTSD may be
      problematic when it is primarily based on a symptom report. Although the forensic
      expert is expected to check the veracity of the symptoms reported, history
      taking, psychopathological assessment and diagnostic accuracy vary greatly among
      professionals. Thus, the diagnosis of PTSD often cannot be confirmed by later
      thorough inspection. Based on more than a decade of civil-forensic work in the
      area, the authors formulate recommendations for independent medical examinations
      in cases of claimed PTSD.

PMID- 19860169
TI  - [The "Interview for evaluation of the psychosocial dimensions of capability
      performance"--a systematic add-on instrument for the expert assessment of work
      capacity (II)].

PMID- 19860170
TI  - [Mentoring system--performance optimization of treatment by formative case
      management].
AB  - The efficiency of the German public health system and its principle of adequate
      treatment are not up to the standards required by accident insurance companies.
      These have to be interested in realising optimal treatment, because the amount of
      pecuniary reparation essentially depends on (the quality of) the state of health
      of the injured person. To accomplish these objectives, their case management
      departments have to find a way to use the resources of the public health system
      and to improve considerably the quality of process und structure of the
      treatment. This is why case management is becoming increasingly important for
      insurance companies. Against this background, this case report describes the
      process of rehabilitation of a 72-year-old woman who had an accident and suffered
      a traumatic brain injury. This process was managed by AMB Generali
      Schadenmanagement GmbH in cooperation with the consulting firm Haase & Johanns
      Consulting, to develop approaches to rehabilitation management. It describes the
      mutual benefit for the injured person and of the insurer, which is defined by the
      success of treatment and saving of costs (care home, damages for pain and
      suffering) amounting to about 700,000 Euros.

PMID- 19860171
TI  - [Visualisation methods for etheric formative forces].
AB  - Rudolf Steiner, the founder of anthroposophy, suggested the development of
      visualisation methods for "etheric formative forces". The essential methods,
      their "spiritual scientific" basis and indications are described and their claims
      critically tested. SUMMARY: The methods are not validated, the key criteria for
      diagnostic tests (reproducibility, sensitivity, specifity) are not given.

PMID- 19860172
TI  - [Reflexology--nothing in common with scientific naturopathic treatments].
AB  - A host of alternative treatment methods are sold to us as reputable science on
      the "supermarket of naturopathy" nowadays. "Foot zone therapy", also known as
      "reflexology" is one of them. Advocates of reflexology claim that certain zones
      of the feet are linked to internal organs; that "energy forces" run throughout
      the human body. According to the teachings of Ayurveda and Yoga, a network of
      more than 72,000 nerve tracts (energy tracts = meridians) is linked to a single,
      tiny point on the feet, where the energy ends. In reality, however, reflexology
      is an unconventional, alternative, paramedical and esoterical "outsider" method
      that has nothing in common with serious naturopathic treatments. Any scientific
      value to reflexology is to be denied. As opposed to reflexology, genuine,
      scientifically acknowledged naturopathic methods are not an alternative, but a
      supplement to modern medicine.

PMID- 19860173
TI  - [Dusseldorf gonarthrosis study of orthokin].

PMID- 19860174
TI  - [Psychological case management in private health insurance--a case report].

PMID- 19860175
TI  - [Comment on K.-D. Block, M Anlauf: The status of scientific medicine].

PMID- 19860176
TI  - [Hematopoietic stem/progenitor cells and leukemia].

PMID- 19860177
TI  - [History, current status, and future prospects in clinical study of myeloid
      leukemia].
AB  - The fundamental principle of the treatment of AML (acute myeloid leukemia) is
      "total cell kill. " For remission induction, "response-oriented individualized
      therapy" was developed in Japan. However, the similar response rate was obtained
      by "set therapy," which became the present standard regimen. Regarding the post
      remission therapy, consolidation therapy is conducted without further long-term
      maintenance/intensification therapy. For poor-risk patients, hematopoietic stem
      cell transplantation should be considered. To improve the therapeutic efficacy,
      the development of molecular targeted therapy will be indispensable. As for CML
      (chronic myeloid leukemia), the development of imatinib has completely changed
      the treatment strategy. The eradication of CML stem cells is the next challenging
      issue.

PMID- 19860178
TI  - [Descriptive epidemiology of myeloid leukemia].
AB  - Epidemiologic information about specific types of leukemia in Japan is limited
      because limited data is available from population-based cancer registry. In this
      review, 1) history of International Classification of Diseases (ICD) about
      hematological malignancies, 2) current situation of population-based cancer
      registry for hematological malignancies, and 3) estimated incidence of acute
      myeloid leukemia (AML) and chronic myeloid leukemia (CML) from selected
      population-based cancer registries (1993-2002 data from 15 registries) are
      presented. Estimated incidence of AML and CML in male and female in Japan are
      approximately half of those from SEER data in the United State. No clear change
      in incidence of AML/CML was observed between 1993 and 2002.

PMID- 19860179
TI  - [Classification of myeloid leukemias].
AB  - Myeloid leukemia in this series corresponds to the myeloid neoplasms of the 4th
      WHO classification of pathology and genetics of tumor of haematopoietic and
      lymphoid tissue. The myeloid neoplasms are composed of six categories, which are
      1) myeloproliferative neoplasms (MPN), a new category of 2) myeloid and lymphoid
      neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1, 3)
      myelodysplastic syndrome (MDS)/MPN, 4) MDS, 5) acute myeloid leukemia (AML) and
      related precursor neoplasms, and 6) acute leukemias of ambiguous lineage. In MPNs
      without chronic myelogenous leukemia, the genetic marker of JAK2 V617F is added
      to the diagnostic criteria for polycythemia vera, essential thrombocythemia and
      primary myelofibrosis. MDS has the new subtype of refractory cytopenia with
      unilineage dysplasia composed of refractory anemia, refractory neutropenia and
      refractory thrombocytopenia. AML with t(9; 11) (p22;q23); MLLT3-MLL, AML with
      t(6;9) (p23; q34); DEK-NUP214, AML with inv(3) (q21q26.2) or t(3; 3) (q21 ;
      q26.2); RPN1-EVI1 and AML (megakaryoblastic) with t(1; 22) (p13; q13); RBM15-MKL1
      are added to the subtype of AML with recurrent genetic abnormalities, and AML
      with gene mutations of NPM1 and CEBPA are also added as provisional entities of
      it. The myeloid neoplasms of the 4th WHO classification are comprehensive and
      seem to be dynamic by incorporating the results of leukemia researches.

PMID- 19860180
TI  - [Cancer stem cell concepts--lesson from leukemia].
AB  - Although monoclonal in origin, most tumors appear to contain heterogeneous
      populations of cancer cells. One possible explanation of this tumor heterogeneity
      is that human tumors are not merely monoclonal expansions of a single transformed
      cell, but rather caricatures of normal tissues, and their growth is sustained by
      cancer stem cells (CSCs). This hierarchy model, first developed for human myeloid
      leukemias, is supported by mounting evidences today. This conceptual shift has
      important implications, not only for understanding tumor biology but also for
      developing and evaluating effective anticancer therapies. We review a history of
      the development of cancer stem cell concepts in hematology and recent topics of
      leukemic stem cells (LSCs).

PMID- 19860181
TI  - [Hematopoietic cell death and leukemia].
AB  - Leukemogenesis is thought to be a multistep process involving changes in the
      expression or abnormalities in the function of proteins encorded by a number of
      genes within the same cell. Such abnormalities affect the balance among cell
      proliferation, differentiation, and programmed cell death (PCD), and this lead to
      an expansion of the malignant clone. Apoptosis (type I PCD) and autophagy (type
      II PCD) are any form of cell death, mediated by an intracellular program, and
      involved in cell homeostasis. However, the mechanism of apoptosis and autophagy
      is extremely complex in leukemia cells, and the molecular machinery is still
      obscure. Therefore, understanding the regulation of apoptotic and autophagic
      signaling pathways could provide important information for the development of
      novel therapies in leukemia cells.

PMID- 19860182
TI  - [Cytogenetic abnormalities and gene mutations in myeloid leukemia].
AB  - Myeloid leukemia is a clinically and genetically heterogeneous disease.
      Cytogenetic studies have revealed specific chromosomal abnormalities, such as
      translocations, and inversions. Fusion proteins derived from these abnormalities
      were identified in various subtypes of leukemia. Because most of these fusion
      proteins were not sufficient to induce leukemia by themselves in mouse models,
      additional oncogenic events have been thought to be necessary for leukemogenesis.
      Recently, a hypothesis called "two-hit model" for leukemia has been proposed. Two
      broad classes of mutations that proliferative or survival advantage of
      hematopoietic progenitors and impaired differentiation are required for inducing
      leukemia. In this article, we summarize some typical chromosomal abnormalities or
      gene mutations associated with myeloid leukemia on the basis of this hypothesis.

PMID- 19860183
TI  - [Radiation-induced and therapy-related AML/MDS].
AB  - Radiation induced acute myeloid leukemia (AML) was recognized a century ago, soon
      after mankind found radiation. Atomic bomb survivors developed de novo AML with
      relatively short latency with very high frequency. By contrast, excess occurrence
      of myelodysplastic syndrome (MDS) as well as solid tumors was found decades late.
      This difference may be due to etiology that many de novo AML patients harbor
      chimeric leukemogenic genes caused by chromosomal translocations, while MDS
      patients rarely carry chimeras. In addition, epigenetic change would play
      important roles. Therapy related leukemia is mainly caused by topoisomerase II
      inhibitors that cause de novo AML with an 11q23 translocation or by alkyrating
      agents that induce MDS/AML with an AML1 point mutation and monosomy 7.

PMID- 19860184
TI  - [Hereditary diseases with propensity to myeloid malignancy].
AB  - Hematological malignancy is known to be associated with Down syndrome (DS),
      neurofibromatosis type 1 (NF1) and congenital bone marrow failure syndromes
      (CBMFS). Although many responsible germ-cell mutations have been identified, the
      secondary mutations that are responsible for the development of myelodysplastic
      syndrome and acute myelogenous leukemia (MDS/AML) have not been determined.
      Additional chromosomal abnormalities such as monosomy 7 and trisomy 21 are often
      observed in the progression to MDS/AML, and the critical genes for monosomy 7
      have recently been reported. In this review, we briefly present recent findings
      regarding DS, NF1 and CBMFS with a tendency for malignant transformation; Fanconi
      anemia, familial platelet disorder with propensity to myeloid malignancy and
      congenital severe neutropenia.

PMID- 19860185
TI  - [Molecular mechanisms in the development of acute myeloid leukemia].
AB  - Acute myeloid leukemia (AML) is a malignant hematopoietic neoplasm characterized
      by clonal proliferation of tumor cells that arise from the hematopoietic
      stem/progenitor population within the bone marrow. Cytogenetic abnormalities or
      point mutations of the hematopoiesis-specific genes are frequently found in
      patients with AML, and these genetic aberrations are closely associated with the
      pathophysiology of the disease. Molecular pathogenesis of AML has been disclosed
      through analyses of such gene aberrations, including AML1 and MLL abnormalities,
      PML-RARA chimeric gene, activating mutations of FLT3, and EVI-1 abnormalities.
      Through prediction of prognosis and targeted therapy, this knowledge on
      pathogenesis of AML has been applied to the clinical practice, and further
      investigation should improve the outcome of therapy for AML in the future.

PMID- 19860186
TI  - [Molecular pathogenesis of chronic myeloid leukemia].
AB  - Chronic myeloid leukemia (CML) is a paradigm for neoplasias that are defined by a
      unique genetic aberration, the BCR-ABL1 fusion gene. CML is also the best example
      for molecular target therapy. The development of protein tyrosine kinase
      inhibitor, imatinib, has entirely changed the strategy of therapy for CML.
      Nonetheless, many fields of pathogenesis for CML have not been elucidated, such
      as the mechanisms of blastic crisis, the causes of genetic instability including
      the inactivation of tumor suppressor genes, and oncogenic signaling pathways
      downstreams of the BCR-ABL1 fusion gene product. Herein, we review current
      knowledge on the molecular pathogenesis of CML.

PMID- 19860187
TI  - [Molecular mechanisms in myeloproliferative diseases and myelodysplastic
      syndromes].
AB  - Little was known about the mechanisms for myeloproliferative diseases (MPD) until
      2005 when an activating mutation in the JAK2 tyrosine kinase (JAK2 V617F) was
      identified in >95% of patients with polycythemia vera (PV), and in a significant
      proportion of patients with essential thormbocythemia (ET) and primary
      myelofibrosis (PMF). Furthermore, activating abnormalities of some tyrosine
      kinases were identified in MPD and related diseases, suggesting that constitutive
      activation of the signaling pathway is a unifying feature of these diseases. On
      the other hand, the molecular mechanism of myelodysplastic syndromes (MDS) is
      still poorly understood. Recent study revealed that two types of AML1/RUNX1
      mutants function via distinct molecular mechanisms to produce mutant-specific
      phenotypes of MDS. The mechanisms of MPD and MDS gradually become clear.

PMID- 19860188
TI  - [Fundamental study of blood and bone marrow].
AB  - The WHO classification incorporated recent advances of immunology, cytogenetics,
      and molecular biology, which developed from FAB classification based on cell
      morphology and cytochemistry. One of the most distinct changes was "AML with
      recurrent genetic abnormalities." The immunological and cytogenetic studies are
      required to apply the classification to hematopoietic and lymphoid neoplasms in
      addition to conventional examinations of the blood and bone marrow. The
      fundamentals of specimen collection, cell counts, morphologic analysis of blood
      cells, special stains and other laboratory studies were described in related to
      the management of myeloid leukemias.

PMID- 19860189
TI  - [Chromosome analysis of and genetic testing for myeloid leukemia].
AB  - The disease-specific chromosomal abnormalities can be observed in various
      hematological malignancies, detected by chromosome analysis and/or genetic
      testing. Genetic testing enables the accurate diagnosis of the type of leukemia
      resulting from chromosome translocation and hence is useful for the choice of
      adequate treatment. Furthermore, genetic testing allows the detection of minimal
      residual disease (MRD) due to its high sensitivity. In recent years, a lot of
      information has been gained on the evaluation of MRD, e.g., the amount of MRD
      corresponding to morphological recurrence or requiring the treatment. Thus, the
      usefulness of MRD quantification at genetic level by real-time PCR has been
      established. At present, however, there is no standard laboratory procedure for
      leukemia genetic testing. Here, the problems related to external precision
      management of this new test are also discussed.

PMID- 19860190
TI  - [Biological markers for diagnosis of myeloid leukemia].
AB  - There are several important biological markers in myeloid leukemia. In
      particular, WT1, FLT3, P-glycoprotein (P-gp) and surface antigens are important
      biologic markers. When we monitor the treatment of leukemia, WT1 is considered to
      be an important marker, and has been applied to immune therapy. The abnormality
      of the genes of FLT3 and expression of P-gp are poor prognostic factors, and
      their inhibitors are developed in progress. The surface antigen analysis of blast
      cells is also used in the classification and the treatment strategy decision.
      Recently, as for the treatment of leukemia, stratification by various kinds of
      factors has been adopted in many prospective studies. The results of these
      biological markers are utilized for the stratification.

PMID- 19860191
TI  - [Combination chemotherapy for acute myeloid leukemia].
AB  - Combination chemotherapy with Ara-C and anthracycline anti-leukemia drugs is a
      standard therapeutics for acute myeloid leukemia (AML) and results in a high rate
      of complete remission (CR). Several salvage therapies have been established for
      relapse/refractory AML cases. In addition, a trial of the combination of
      chemotherapy with gemtuzumab ozogamicin for poor-risk AML is ongoing. The
      development of a new strategy including combination of conventional anti-leukemia
      drugs with molecule-targeting reagents might be needed to increase CR rate and
      cure rates by combination chemotherapy. Development of therapeutics to eradicate
      leukemia stem cells is also of important for increasing the cure rate of AML.

PMID- 19860192
TI  - [Clinical use of tyrosine kinase inhibitors for treatment of myeloid leukemias].
AB  - Imatinib mesylate, a selective Ab1 tyrosine kinase inhibitor (TKI), is the first
      choice of therapy for CML and has been dramatically improving the prognosis of
      patients with chronic phase CML. Now that second generation TKIs including
      nilotinib and dasatinib is available for imatinib-intolerant or resistant
      patients, the therapeutic algorithm should be revised and updated. As for AML, a
      number of clinical trials using TKIs targeting FLT3, whose internal tandem
      duplication is one of the poor prognostic factors in AML, are in progress and
      FLT3 inhibitors in combination with chemotherapeutic agents will be promising for
      relapsed and refractory patients in the near future.

PMID- 19860193
TI  - [Current clinical trials using new targeted therapies for myeloid leukemia and
      the research trends].
AB  - Great progress on insight into genetic aberrations of myeloid leukemia via gene
      expression profiling has led to better understanding of the pathobiology of this
      heterogeneous disorder. It enabled the development of specific treatment
      modalities targeted to underlying oncogenic abnormalities, with well established
      examples of all-trans retinoic acid for the treatment of acute promyelocytic
      leukemia and imatinib for chronic myeloid leukemia. However, these strategies
      have not been completely developed yet in that most of brand new targeted
      therapies have been somewhat far from achieving cure of leukemia and that many
      problems with regards to drug resistance and recurrence from minimal residual
      disease remain to be solved. On the other hand, concept of cancer(leukemic) stem
      cell and its niche has been shedding new light on oncological field these days.
      This review summarizes the current clinical trials using new targeted therapies
      and research trends on myeloid leukemia.

PMID- 19860194
TI  - [Immunotherapy and cell therapy for myeloid leukemia].
AB  - To develop effective cellular immunotherapy for hematopoietic malignancies, the
      tumor-associated antigens that are recognized by cytotoxic T lymphocytes (CTL)
      must be identified. Recently, various leukaemia-associated antigens that are
      recognized by CTL in the context of HLA class I molecules have been identified.
      These include fusion gene products such as BCR-ABL and ETV6-AML1, proteinase 3,
      WT1, human telomerase reverse transcriptase, cyclophilin B, and PRAME. In
      addition, various target antigens associated with other hematopoietic
      malignancies have been also identified. On the basis of these findings, various
      clinical trials of immunotherapy for hematological malignancies, including
      peptide vaccination, dendritic cell therapy, adoptive transfer of CTL, T-cell
      receptor gene therapy have been ongoing. Here, the current status and future
      feasibility of cellular immunotherapy for leukemia are discussed.

PMID- 19860195
TI  - [Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia-
      recent progress].
AB  - Allogeneic stem cell transplantation represents the most active form of anti
      leukemic therapy in acute myeloid leukemia (AML). Advances in the transplant
      technology, availability of hematopoietic stem cells and supportive care not only
      have resulted in improved outcomes but also expanded the transplant options.
      However, post-transplant relapse and transplant-related mortality, especially
      those associated with allo-immune reaction after transplantation, remain as the
      leading causes of failure of this therapeutic approach. This review is going to
      focus on the recent progress to selectively enhance the anti-AML activity of
      conditioning and post-transplant allo-immune reaction.

PMID- 19860196
TI  - [Supportive therapies for myeloid leukemia including blood transfusion and growth
      factors].
AB  - Bone marrow suppression after intensive chemotherapies in patients with myeloid
      leukemia is severe, resulting in the reduction of the number of white blood
      cells, red blood cells, and platelets. Supportive therapies are indispensable for
      the management of these leukemia patients. The improvement of blood cell
      transfusion can decrease side effects of chemotherapies and establish the safety.
      But we still have notable side effects of transfusion such as TRALI (transfusion
      related acute lung injury), platelet immunologic refractory state, and so on.
      Cytokine therapy especially with G-CSF (granulocyte colony-stimulating factor)
      administration, changed the treatment of myeloid leukemia. G-CSF can shorten the
      duration of neutropenia and decrease the risk of infection. Recently the effects
      of Epo (erythropoietin) on chemotherapy-induced anemia have been demonstrated. We
      discuss here the indications of blood cell transfusion and cytokine therapies in
      the treatment for myeloid leukemia.

PMID- 19860197
TI  - [Gene therapy for myeloid leukemia].
AB  - Among several immune-gene therapies against myeloid leukemia, "T cell depleted
      haplo-identical transplantation with HSV-TK gene modified T cell add-back" and
      "donor lymphocyte infusion using HSV-TK gene modified T cell in patients
      experiencing recurrence after allogeneic stem cell transplantation" were in
      advanced stages of clinical development. In this chapter, I will summarize the
      strategies of gene therapy using HSV-TK gene modified T lymphocyte in allogeneic
      stem cell transplantation. I will also point out the current situation of other
      gene therapies such as cytokine gene modified CML-DC and TCR gene modified T
      lymphocyte against myeloid leukemia.

PMID- 19860198
TI  - [Treatment of myeloproliferative neoplasms other than chronic leukemia].
AB  - The discovery of JAK2 mutation has greatly facilitated the approach to diagnosis
      of myeloproliferative neoplasms besides chronic myeloid leukemia. Since major
      causes of morbidity and mortality in polycythemia vera (PV) and essential
      thrombocythemia (ET) are represented by thrombosis, bleeding, progression to
      myelofiblosis, and tranfromation to leukemia, risk oriented therapeutic approach
      is recommended. Established risk factors for cardiovascular events are
      represented by older age (age over 60) and previous thrombosis. While there are
      some concerns, the JAK2 mutational status as well as mutant allele burden might
      be a new surrogate marker for stratified management of PV and ET. Finally, there
      is a great expectation for novel drugs targeting the constitutively active
      JAK2/STAT pathway.

PMID- 19860199
TI  - [Management of microbial infections in myeloid leukemia].
AB  - The management of microbial infection is one of the important issues for patients
      with acute myeloid leukemia (AML). They are considered to be at high risk for
      infection. They should be provided appropriate antimicrobial agents recommended
      by the Infectious Diseases Society of America (IDSA). Recently, there have been
      several significant changes in IDSA guidelines especially in the treatment of
      invasive fungal infection because of developments in several antifungal agents.
      This document constitutes the recommendations for the management of infection in
      patients with AML according to the updated guidelines of the IDSA. Evidence about
      infection control in AML is not enough in contrast to hematopoietic stem cell
      transplantation. Further studies are necessary to establish the strategy for
      microbial infections in AML.

PMID- 19860200
TI  - [Management of anemia and bone marrow hypoplasia in the treatment of myeloid
      leukemia].
AB  - It is important for achieving complete remission of acute myelogenous leukemia to
      manage anemia and bone marrow hypoplasia, which cause serious complications.
      Anemia and bone marrow hypoplasia are mainly treated by supportive therapies
      consisting of granulocyte-colony stimulating factor, red blood cell transfusion
      and platelet transfusion, which are given according to recommendations of
      guidelines. In addition to these supportive therapies, new drugs such as DNA
      demethylating agents are developed for myelodysplastic syndrome (MDS). These
      drugs are expected to improve a cytopenia, and reduce the frequency of
      transfusions.

PMID- 19860201
TI  - [Treatment of DIC associated with myelogenous leukemia].
AB  - Many hematologists believe that anti-tumor drugs and platelet transfusion are
      enough for the treatment of disseminated intravascular coagulation (DIC)
      associated with myelogenous leukemia. In this paper, showing the pathophysiology
      of 3 types of DIC, I insisted the necessity of anticoagulant therapy to avoid the
      bleeding death or ischemic organ damage before achieving the hematological
      remission, because myelogenous leukemia is now a curable disease. In addition, I
      introduced the new Japan-made weapon to DIC, recombinant thrombomodulin, which
      complexes with thrombin and regulates the coagulation activity by efficient
      activation of protein C. Using two different natural anticoagulant systems,
      antithrombin and protein C pathway, we can more effectively improve DIC treatment
      and alleviate symptoms in DIC patients.

PMID- 19860202
TI  - [Humanized model for acute myeloid leukemia].
AB  - To investigate human hematopoiesis and immunity in vivo, we have been making
      efforts to reconstitute these systems in mice by intravenously injecting purified
      human stem cells into NOD/SCID/IL2rgKO newborns. This xenogeneic transplantation
      system supports long-term engraftment, multi-lineage differentiation, and self
      renewal capacity of human cord blood-derived hematopoietic stem cells (HSCs). We
      here introduce our recent application of the NOD/SCID/IL2rgKO newborn
      xenotransplant system to create in vivo models for human hematological
      malignancies and to understand pathophysiology of human AML.

PMID- 19860203
TI  - [Clinical problems in the treatment of myeloid leukemia in childhood].
AB  - As for childhood AML, intensification of chemotherapy and advance in supportive
      care have contributed toward the patient survival. In addition to prevent early
      death, we have to develop a risk classification and appropriate therapies with
      updated genomics, especially for the intermediate risk group which has much
      diversity. Also, new treatment strategies utilizing various molecular-targeted
      therapies are required. For childhood CML, the possibilities of unknown risks
      which accompanied by life-long imatinib treatment should be considered. Comparing
      SCT and imatinib, We need to make an original treatment guideline for child CML.
      Furthermore, according to the increase of long-term survivors, the late adverse
      effects showed up. We should aim for "full recovery" and hope to have a long-term
      follow up and feedback system for the survivors.

PMID- 19860204
TI  - [Characteristics of elderly patients with acute myelogenous leukemia].
AB  - The average life span of our country is the longest in the world, and rapid aging
      is taking place, besides. Therefore the elderly patients with acute myelogenous
      leukemia (EAML) is increasing. The biological characteristic of EAML is
      deteriorating internal organs function, and high ratios having the complication
      of the patient. Leukemic cells in the elderly has the biologic characteristic
      that non-usual case, for example hypoplastic leukemia, is many, and a case having
      abnormal chromosomal aberration is also. A social characteristic of EAML is that
      they are treated at a general hospital such as the municipal hospital not a
      university hospital, and in many cases the only family is the elderly spouse.
      Enough understanding of the nation is necessary to overcome such a
      disadvantageous point and to improve treatment results of EAML.

PMID- 19860205
TI  - [Current topics in stroke research].
AB  - This review summarizes current topics for brain protection against stroke.
      Although there has been no strategy for brain protection except for tissue
      plasminogen activator, recent advance in neuroscience has addressed subtypes of
      glutamate receptor on neuronal survival and death. Hypothermia and ischemic
      tolerance are the most reproducible strategies for brain protection in
      experimental ischemia, and they share metabolic down-regulation as a crucial
      factor for protective action. Development of collateral circulation
      (arteriogenesis), endogenous neurogenesis after ischemia, gene therapy and cell
      transplantation are all potential targets for developing a new strategy for
      stroke patients.

PMID- 19860206
TI  - [Evaluation of antihypertensive effect of angiotensin II receptor blockers in
      patients with essential hypertension by self-measured home blood pressure-
      HACARARE 300 study].
AB  - We enrolled outpatients who had been newly diagnosed as hypertension or who had
      already taken the antihypertensive medicine in 62 medical institutions of the
      Toyama prefecture in the present study. Three hundred twenty-four hypertensive
      outpatients who were taking candesartan cilexetil(candesartan) were followed for
      about 12 weeks and the blood pressure(BP) lowering effect of candesartan was
      evaluated by self-measured home BP levels and office BP levels. Both self
      measured morning and evening home BP and office BP showed a significant reduction
      four weeks later by administration of candesartan to the hypertensive
      outpatients, and this BP lowering effect was maintained until the final visit.
      Regardless of the mode of administration of candesartan (initial therapy to drug
      naive, up-titrated therapy, combination therapy with others, and switching
      therapy from others), BP lowering effect was shown similarly in each therapy.
      Because administration of candesartan at appropriate dosage (4-12 mg/day)
      significantly decreased self-measured morning home BP, candesartan might possess
      the property to maintain a sustained BP reduction for up to 24 hours after
      dosing, and might be able to prevent early morning cardiovascular events.

PMID- 19860207
TI  - [Harmonization procedures directed toward clinical trials in laboratory medicine
      at the National Cancer Center Hospital].
AB  - Recent advances in pharmacology and molecular sciences made it possible to
      develop drugs for patients with various maladies. Frustration has existed
      concerning the delayed provision of these drugs for routine practices in the
      clinical field. To correct this problem, the importance of clinical trials is
      increasing. Although there exists a strong demand for participation of clinical
      laboratories in clinical trials, an awkward attitude in clinical laboratories
      frustrates those performing clinical trials. We are attempting to correct this
      problem by introducing our experience with harmonization procedures directed
      toward clinical trials in laboratory medicine in general. First we described the
      current status of clinical trials in our hospital. Then we will show personnel in
      need for clinical trials. Finally we describe in detail our clinical trial
      procedures. We focus particularly on three aspects of participation in clinical
      trials: pre-analytical, analytical, and post analytical. Additionally we describe
      the problems and perspectives in clinical trials by giving special reference to
      the clinical laboratories in general through discussion with various personnel
      and specialists. Our goal in the field of laboratory medicine is to benefit
      patients through the establishment of a harmony between clinical trials and
      clinical laboratories.

PMID- 19860208
TI  - [Influence of commercial soft drinks or green tea intake to occult blood and
      sugar tests with urinalysis reagent strips].
AB  - Consumption of commercial soft drinks or tea has increased in over recent years.
      In many case, these drinks contains large amount of ascorbic acid as an
      antioxidant. We examined the influence of ascorbic acid to the result of urine
      occult blood and sugar tests with urinalysis reagent strips. Three subjects took
      3 brands of soft drinks (P, C, B) in 3 different days once in the morning. Other
      3 subjects took 4 brands of green tea in 4 different days 4 times in a day. After
      2 hours of first administration, urine specimen were collected every hour for 8
      10 hours. Constant amount of hemoglobin or sugar was added in urine specimen and
      the reflectance was measured with AX-4280. As a results, urine ascorbic acid
      induced false negative results in both occult blood and sugar tests in all
      groups. These results indicate the necessity of patient education about
      commercial soft drinks or green tea consumption on the previous night and the day
      of the urinalysis.

PMID- 19860209
TI  - [Problems with carrying out the communalization of reference intervals: from the
      results of a questionnaire survey sent out by the Society of the Hitachi
      Automatic Clinical Analyzer].
AB  - The measurement systems in clinical laboratory tests are being standardized, and
      variations in measurement values such as those of clinical chemistry tests among
      institutions have decreased. Though the compatibility of clinical tests' values
      is being established, reference intervals differ among institutions. Therefore,
      to clarify problems for the standardization of reference intervals, the Society
      of the Hitachi Automatic Clinical Analyzer sent out a questionnaire survey on
      problems regarding standardization in institutions. The questionnaire consisted
      of 40 items relating to blood examination, clinical chemistry tests, and
      immunological examination. 27 institutions responded. The results of the
      questionnaire showed that many institutions look favorably upon the
      standardization of reference intervals. However, they had a cautious attitude
      regarding the establishment of the reference intervals for items showing
      differences in reactivity among reagent kits or having no wide-spread measurement
      system. They appeared to consider that the standardization process is accompanied
      by many difficulties. Unless the nationwide standardization of reference
      intervals is achieved at the scientific society level, approval on the clinical
      side may be difficult to obtain. How to obtain clinical understanding is a
      problem. Nationwide data sharing has been advanced, and the standardization of
      reference intervals should also be advanced at the national level.

PMID- 19860210
TI  - [Diagnosis and therapy in NASH].
AB  - Non-alcoholic fatty liver disease (NAFLD) has recently been recognized as a
      leading cause of abnormal liver function tests. Its spectrum ranges from simple
      steatosis, which is usually a benign and non progressive condition, to non
      alcoholic steatohepatitis (NASH), which may progress to cirrhosis and
      hepatocellular carcinoma. NASH is thought to be almost 10% of NALFD and part of
      metabolic syndrome. NASH patients usually have insulin resistance, frequently
      combined with hypertension, hyperlipidemia and diabetes. The etiology of NASH
      remains unclear, but most investigators agree that the development of NASH
      requires underlying steatosis followed by a "second hit" that induces
      inflammation, fibrosis, or necrosis. The interaction of adipocytokines (TNF
      alpha, adiponectin) with oxidative stress and lipid peroxidation has been
      postulated to play a key role in NASH. The basic therapy for NASH is an improved
      of lifestyle, including exercise and diet. Drug therapy should be considered as
      additional therapy.

PMID- 19860211
TI  - [Autoimmune pancreatitis].
AB  - Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by
      high serum IgG4 concentrations and abundant IgG4-bearing plasma cell infiltration
      in the pancreatic lesion. This disease is based on the clinical features of
      histological evidence of lymphoplasmacytic sclerosing pancreatitis and fibrosis,
      irregular narrowing of the pancreatic duct, and a favorable response to
      glucocorticoid treatment. The initial prednisone dosage is 30 to 40 mg/day,
      tapered in 5-mg reductions every one to two weeks. Other features of this disease
      involve a variety of extra-pancreatic complications seen in sclerosing
      cholangitis, Mikulicz disease, as manifested by lachrymal and salivary gland
      swellings, hilar lymphadenopathy, and retroperitoneal fibrosis. Some of these
      extra-pancreatic lesions show pathological findings similar to those of
      pancreatic lesions, including infiltration by abundant IgG4-bearing plasma cells.

PMID- 19860212
TI  - [Crucial roles of Helicobacter pylori infection in the pathogenesis of gastric
      cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma].
AB  - Helicobacter pylori (H. pylori) is a gram-negative helical rod that colonizes
      human gastric mucosa. Its discovery has opened up new opportunities regarding the
      understating and management of gastrointestinal disorders. In humans, infection
      with H. pylori has been established as a major cause of chronic gastritis and
      peptic ulcer, and is important in the pathogenesis of gastric cancer and gastric
      mucosa-associated lymphoid tissue (MALT) lymphoma. Bacterial and host factors
      determine the outcome of H. pylori infection. The eradication of H. pylori can,
      therefore, contribute to the treatment and prevention of these diseases. H.
      pylori infection plays a critical role in gastric carcinogenesis through two
      major pathways: the indirect action of H. pylori on gastric epithelial cells
      through inflammation, and the direct action of the bacteria on epithelial cells
      through the induction of protein modulation and gene mutation. MALT lymphoma is a
      common low grade B-cell lymphoma arising from a background of chronic
      inflammatory disease at a number of mucosal sites. Those originating in the
      stomach are causatively linked to H. pylori infection, and eradication of the
      bacterium with antibiotics leads to the long-term complete regression of
      lymphoma. t (11;18)/API2-MALT1 and t(1;14)/IGH-BCL10 are specifically associated
      with the gastric MALT lymphoma entity, and the oncogenic products of these
      translocations have been shown to target a common molecular pathway, i.e., the
      nuclear factor-kappaB pathway. This paper reviews recent advances in our
      understanding of the association of H. pylori infection with gastric cancer and
      gastric MALT lymphoma and the molecular genetics underlying tumor development.

PMID- 19860213
TI  - [H. pylori infection and extra-digestive disease--idiopathic thrombocytopenic
      purpura and iron deficiency anemia--review].
AB  - Although H. pylori infection has been shown to be associated with a wide variety
      of non-gastrointestinal tract conditions, the studies are conflicting regarding
      these associations. In addition, a biological rationale for the proposed
      association with H. pylori infection is often lacking. Recent systematic reviews
      have shown a beneficial effect of H. pylori eradication in idiopathic
      thrombocytopenic purpura. The weighted mean complete response (platelet count >
      or = 100 x 10(9)/L) and overall response (platelet count > or = 30 x 10(9)/L and
      at least doubling of the basal count) were 42.7% (95% confidence interval[CI],
      31.8%-53.9%) and 50.3% (95% CI, 41.6%-59.0%), respectively. These recent reviews
      demonstrated that diagnosis and treatment of H. pylori infection should be
      considered; however, randomized controlled clinical trials and immunological
      investigations on the mechanism are still lacking and are required. The results
      of meta-analysis indicated a significant association between H. pylori infection
      and iron deficiency or iron deficiency anemia, especially in high-risk groups.
      Although some case studies, small patient series and non-randomized trials have
      shown a beneficial effect of eradication in children with iron deficiency anemia,
      negative findings have also been reported. Further evaluation of the improvement
      of iron stores by eradication in large and well-controlled trials are required
      and would allow further additional studies to understand its biological
      mechanisms.

PMID- 19860214
TI  - [Bone quality markers: pentosidine, homocysteine, and MTHFR polymorphism].
AB  - Bone quality is thought to encompass the structural and material properties of
      bone that are affected by the turnover rate. Evidence has accumulated that
      collagen cross-links play important roles in bone strength. We have demonstrated
      that the quantitative and qualitative deterioration of lysyl oxidase control and
      non enzymatic cross-links (advanced glycation end products, AGEs, pentosidine) of
      collagen in patients with osteoporotic femoral neck fracture might be affected by
      hyperhomocysteinemia, oxidative stress, and vitamin B6 insufficiency. Recently,
      Shiraki et al. demonstrated that a functional polymorphism in
      methylenetetrahydrofolate reductase (MTHFR) polymorphism, T allele (C677T), may
      be a risk factor for future fracture in addition to the traditional risk factors.
      Further, we reported that a higher urinary pentosidine level was an independent
      risk factor for vertebral fracture in a 5-year prospective study involving
      Japanese women. If confirmed in large, prospective trials, measurements of serum
      homocysteine and serum or urine levels of pentosidine might be characterized as
      markers reflecting bone collagen deterioration.

PMID- 19860215
TI  - [Inspection data required for specific health checkups].
AB  - Since 2008, specific health checkups and health care advice have been performed
      as part of medical system reforms. The Ministry of Health, Labour and Welfare
      translated "Tokutei kenko shinsa/tokutei hoken shido" as "Health checkups and
      health care advice with a particular focus on the detection of diabetes for all
      those insured over the age of 40". Therefore, specific health checkups and health
      care advice can be considered to aim at preventing diabetes mellitus due to a
      rapid increase in the number of patients with this disease and high-risk persons.
      After the introduction of this system, measurement values and evaluation criteria
      common to medical institutions providing these checkups and health care advice
      became necessary. Therefore, the standardization of clinical examination values
      as a longstanding problem in the clinical laboratory was initiated from the
      health checkup section, which underwent various reforms associated with specific
      health checkups.

PMID- 19860216
TI  - [Reference value for metabolic syndrome checkup and some problems].
AB  - Metabolic syndrome is one of the most important risk factors of atherosclerotic
      disease, and visceral obesity is regarded as a principle component of metabolic
      syndrome. Medical checkups for metabolic syndrome were started in 2008 for the
      purpose of promoting lifestyle modification through health guidance. The original
      diagnosis of metabolic syndrome in Japan was presented by the Examination
      Committee of Criteria for Metabolic Syndrome in April 2005. This guideline
      defines the waist circumference measurement as an essential component,
      accompanied by at least two of the following three risk factors: dyslipidemia, a
      raised blood pressure, and glucose intolerance, and these risk factors were based
      on multiple representative Japanese cohort studies. However, there are some
      problems with these standards. For example, it is often the case that accurate
      evaluation is difficult because variable factors such as meals influence the
      serum triglyceride level. This influences the reliability of the results of
      cohort studies. In this symposium, problems with this guideline were presented
      along with an introduction to the cohort study on which the concept of the
      syndrome was based. I compiled a cohort study related to metabolic syndrome, and
      pointed out some problems from the viewpoint of clinical laboratory medicine.

PMID- 19860217
TI  - [Activities of Japanese Committee for Clinical Laboratory Standards (JCCLS)
      toward standardization of laboratory medicine].
AB  - In this review, we summarize the laboratory medicine standardization activity of
      the Japanese Committee for Clinical Laboratory Standards (JCCLS). The JCCLS
      cooperates with the Joint Committee for Traceability in Laboratory Medicine
      (JCTLM). In the near future, we will accomplish a nationwide network system for
      the standardization of laboratory medicine (Patchwork Standardization-System).

PMID- 19860218
TI  - [Quality assessment scheme required in health checkups and healthcare advice
      proposed by Ministry of Health, Labour and Welfare].
AB  - Quality control schemes are essentially required for the health check programs
      proposed by the Ministry of Health, Labour and Welfare. As you know, quality
      assessment schemes can be divided into two concepts, one is an internal quality
      control scheme-managed intra-laboratory measurement system, and the other is an
      external quality control system managed between laboratories with acceptable
      error levels of measurement systems. Today, the two concepts of uncertainty and
      traceability have been newly introduced into laboratories. Ways to employ these
      two concepts in laboratories for health check programs are described and
      discussed in this paper. In the case of internal quality control, the concept of
      uncertainty is very important for laboratories, because it clearly identifies the
      sources of error in laboratories. On the other hand, the concept of traceability
      is important for the use of calibrators to reduce measurement disparities between
      laboratories. The correct use of calibrators traceable to SI or values
      internationally agreed upon regarding standard materials markedly reduce inter
      laboratory gaps in measurement systems. We discuss the correct use of calibrators
      and the uncertainty concepts in the field of health check programs proposed by
      the Ministry of Health, Labour and Welfare.

PMID- 19860219
TI  - [HPV and cervical cancer examination--prospects in cervical cancer examination].
AB  - Cervical cancer is caused by infection with human papillomavirus (HPV),
      discovered by Zur Hausen, a 2008 Nobel laureate in medicine. Regular examination
      is essential for the prevention of cervical cancer. Two problems have been
      pointed out regarding cervical cancer examination in Japan: low rates of
      participation in the examination, and the accuracy of cytological diagnoses. If
      HPV testing is conducted in combination with cytological diagnoses performed at
      present, it is estimated that higher levels of screening accuracy will be
      achieved, and almost 100% of cervical cancer will be detected as a precancerous
      lesion. Moreover, an HPV vaccine was developed. The incidence of cervical cancer
      is expected to decrease almost to zero in the near future because of increased
      awareness of HPV vaccination and cancer screening including HPV testing. In this
      symposium, four specialists will give lectures on present cervical cancer
      examinations, including methods for the cytological diagnosis and reporting
      forms, and their problems. We will also discuss prospects in HPV testing and
      cervical cancer examination.

PMID- 19860220
TI  - [Updated cervical cancer screening; human papilloma virus and Papanicolaou
      tests].
AB  - Cervical cancer screening using Papanicolaou test (Pap) previously reduced the
      incidence of and mortality from cervical cancer in Japan. However, this reduction
      stopped from 1990, and the incidence increased in 2001. Furthermore, the age of
      women developing cervical cancer has decreased, and the mortality rate in women
      aged from 25-54 years increased from 1994 to 2003. We conducted research
      regarding women aged from 20 to 59 years, demonstrating that the coverage of
      cervical cancer screening within the last three years in Japan is 33%. This is
      less than half of that in many developed countries. Many recent studies have
      revealed that the sensitivity of the Pap test for screening has been over
      estimated. Our preliminary study in Japan also revealed that more than 29% of
      CIN2 or more advanced lesions were missed in one screening, although this rate
      differed depending on the experience or ability of each cyto-screener. To
      compensate for this limitation in Pap test, the HPV-DNA test has been introduced
      in cervical cancer screening in both developed and developing countries. Both Pap
      test and the HPV test are used as primary screening tools in women older than 30
      years in the U.S.A. The interval of this screening can extend to three years if
      both tests are negative. A primary HPV screening program is due to start in the
      U.K. and Holland. The increasing incidence of cervical cancer in Japan prompts us
      to make efforts to increase the coverage of cervical cancer screening, and the
      HPV test should also be incorporated into screening programs.

PMID- 19860221
TI  - [The significance of the combined usage of cytology and the HPV test in cervical
      cancer screening].
AB  - BACKGROUND: In the United States, the combined usage of cytology and the HPV test
      is employed in cervical cancer screening, but, in Japan, only cytology is
      performed in most cases. We conducted a comparative analysis of histopathological
      diagnoses by colposcopy, cytology, and the HPV test, and evaluated the
      effectiveness of cytology and the significance of its combined use with the HPV
      test. METHODS: We compared the detection rates using the test for high-risk HPV
      and cytology, which were conducted in cases with various histological diagnoses.
      The hybrid capture method was used in the HPV test. The blind test was conducted
      by 3 cytologists in 14 cases in which the cytological differed from the
      histological diagnosis by more than 2 classes. RESULTS: There were 89 cases above
      class IIIb or CIN 3, and 26 cases were below class IIIa. A total of 107 cases
      were positive on the HPV-DNA test, and 8 cases were negative. CONCLUSION:
      Cytology is essential as a morphological diagnostic method in cancer screening.
      In contrast, the HPV test detects the cause of cervical cancer. Therefore, the
      combined usage of cytology and the HPV test as initial screening for cervical
      cancer would facilitate the diagnosis of a premalignant lesion or early-stage
      cervical cancer more promptly and accurately.

PMID- 19860222
TI  - [Effect of anesthetics on malignant tumor cells (A review)].
AB  - The influence of surgery and anesthesia on aspects of malignant tumor has
      received considerable attention in recent years. It is suggested that in vitro
      studies, clinically available anesthetics, such as intravenous anesthetics, local
      anesthetics and opioids have, more or less, possible antitumor potential against
      human malignant tumor cells. Although natural killer (NK) cells play an important
      role in tumor and metastasis surveillance, the reported effects of the
      anesthetics on the NK cell activity in human are controversial. Animal studies
      indicate that the neuroendocrine stress response to the surgery suppresses the
      immune function, particularly NK cell cytotoxicity, and increases the metastatic
      burden under inhalational anesthesia alone. Moreover, animal studies indicate
      that the addition of spinal block and optimum postoperative analgesia
      independently reduce the metastatic burden by blocking the stress response under
      inhalational anesthesia alone. Considering inconclusive results, especially in
      human, about evaluating the influence of anesthetics on malignant tumor, further
      studies in basic and clinical settings are required to study the effects of
      anesthetics on malignant tumor.

PMID- 19860223
TI  - [Reliability of propofol target-controlled infusion in obese patients].
AB  - BACKGROUND: Propofol target-controlled infusion (TCI) is now commonly used for
      induction and maintenance of anesthesia. In this study, we measured the propofol
      plasma concentrations in obese patients in order to test our hypothesis that
      propofol TCI is reliable for use in obese patients. METHODS: We measured plasma
      concentrations of propofol in 10 obese patients undergoing elective general
      anesthesia. Propofol TCI was commenced at a target plasma concentration of
      4microg x ml(-1) using a TCI pump. The target concentration was kept at 4microg x
      ml(-1) for at least 3 hours. Arterial blood samples were drawn for measurement of
      the propofol plasma-concentration analysis at 30, 60, 90, 120 and 180 minutes
      after the induction of anesthesia, and at the emergence from anesthesia. RESULTS:
      The measured plasma concentrations of the drug were not significantly different
      from the target plasma concentrations and they showed no tendency to increase
      during the 3 hours of anesthesia. The measured plasma concentration at emergence
      was lower than the estimated value. CONCLUSIONS: We conclude that propofol TCI is
      a reliable method for maintaining anesthesia even in obese patients. At
      emergence, however, the data suggested that the plasma concentrations might be
      lower than the estimated values in obese patients.

PMID- 19860224
TI  - [Anesthetic management with remifentanil infusion during laparoscopic
      cholecystectomy].
AB  - BACKGROUND: In the anesthetic management of laparoscopic surgery, hemodynamic
      changes appear on the skin incision and pneumoperitoneum. Remifentanil may
      suppress the cardiovascular changes on the pneumoperitoneum in the laparoscopic
      cholecystectomy (LC). METHOD: One hundred-seven patients scheduled for LC were
      assigned into two groups; remifentanil (R), and epidural (E) groups. In R group,
      remifentanil was administered at 0.2 microg x kg(-1) x min(-1) from the induction
      of anesthesia. In E group, an epidural catheter was placed between T10-12 and
      0.2% ropivacaine was infused continuously at 6 ml x hr(-1) via epidural catheter.
      Anesthesia was maintained by propofol at 5 mg x kg(-1) x hr(-1) following the
      induction by propofol and vecuronium in both groups. Heart rate (HR), systolic
      blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure
      (MAP) and bispectral index (BIS) were compared at the entrance of the operating
      room, skin incision, pneumoperitoneum and extubation of the endotracheal tube
      between two groups. RESULTS: At the pneumoperitoneum, statistical significance
      was found in HR, but there was no significant difference in blood pressure and
      BIS between the two groups. CONCLUSIONS: Compared with epidural anesthetic
      management, remifentanil suppresses significantly the elevation of heart rate,
      but not blood pressure at the pneumoperitoneum.

PMID- 19860225
TI  - [Breathing pattern and postoperative analgesia at various effect-site
      concentrations of fentanyl].
AB  - BACKGROUND: We investigated how various effectsite concentrations of fentanyl
      could affect breathing pattern and postoperative analgesia. METHODS: This study
      enrolled 64 ASA physical status 1 and 2 patients, undergoing elective surgical
      procedures, including otologic, orthopedic, breast surgery and gynecological
      laparoscopic procedure. General anesthesia was performed with sevoflurane
      inhalation and target-controlled infusion for fentanyl. After the surgery,
      fentanyl was administered by a target-controlled infusion system to maintain one
      of the effect-site concentrations of fentanyl as follows ; 0.5, 0.8, 1.0, 1.2,
      1.5, 1.8 and 2.0 ng x ml(-1) under 0.8% of the end-tidal sevoflurane
      concentration. We recorded spontaneous respiratory rate (RR), tidal volume (Vt),
      and minute volume (MV). After sevoflurane inhalation was finished, the end-tidal
      sevoflurane concentration at the time at which they responded to command was
      recorded. Postoperative pain was assessed right after extubation. RESULTS:
      Although RR decreased in a effect-site concentration of fentanyl dependent
      manner, V(T) increased gradually, resulting in relatively constant range between
      0.5-2.0 ng x ml(-1) of effect-site concentration of fentanyl. Postoperative pain
      was adequately controlled in the range between 1.2-2.0 ng x ml(-1) of effect-site
      concentrations of fentanyl. CONCLUSIONS: According to our data, 1.2-2.0 ng x ml(
      1) of effect-site concentration of fentanyl could provide adequate postoperative
      analgesia without respiratory depression in otologic, orthopedic, breast surgery
      and gynecological laparoscopic procedures.

PMID- 19860226
TI  - [Evaluation of the relation between the depth of left double-lumen endobronchial
      tube and the patient's height--comparison between patients over 20 years of age
      and those under 19 years].
AB  - BACKGROUND: In adult patients, there is a strong correlation between the
      appropriate depth of insertion of a left double-lumen endobronchial tube (DLT)
      and height. However, for patients with the same height, we noted the tendency of
      the depth of insertion being about 1 cm shorter for patients under 19 years of
      age compared to that for those over 20 years. METHODS: We compared the depth of
      insertion between patients over 20 years and those under 19 years. RESULTS: In
      both groups, the depth of DLT insertion correlated strongly with patient's
      height. For patients of the same height, the depth of insertion for those under
      19 years was 0.7-1.2 cm shorter than that for patients over 20 years. For
      patients with a height between 160-179 cm, the mean depth of insertion for
      patients under 19 years was significantly shorter than that for those over 20
      years. CONCLUSIONS: During intubation of the bronchi with DLT in patients under
      19 years, the optimal depth of DLT insertion is less than that for patients over
      20 years.

PMID- 19860227
TI  - [Efficacy of traditional herbal medicine, Yokukansan on patients with neuropathic
      pain].
AB  - BACKGROUND: Neuropathic pain that is the chronic, severe, and intractable pain,
      interferes with activities of daily living (ADL) and consequently reduces quality
      of life (QOL). We reported the efficacy of Yokukansan in patients with
      neuropathic pain, including acute herpetic pain, postherpetic neuralgia, central
      poststroke pain, post-traumatic spinal cord injury pain, thalamic syndrome,
      complex regional pain syndrome and symptomatic trigeminal neuralgia. Yokukansan
      was more effective compared with traditional medicines, such as tricyclic
      antidepressants, carbamazepine, gabapentin, and opioids etc., which are
      recommended to treat neuropathic pain. Recently, effects of Yokukansan is
      reported on the behavioral and psychological symptoms of dementia (BPSD) in
      elderly patients with dementia. Repeated administration of Yokukansan decreases
      expression of 5-hydroxytryptamine (5-HT) 2A receptors in the prefrontal cortex in
      mice, and Yokukansan also protects destruction of myelin sheaths in rats with
      thiamine deficient-induced encephalopathy. Mechanism of effectiveness of
      Yokukansan on neuropathic pain has not been established; however, efficacy of
      Yokukansan on neuropathic pain has been shown clinically. CONCLUSIONS: As far as
      we know, this is the first report that Yokukansan was effective on neuropathic
      pain. Yokukansan without serious adverse reactions may be a possible medicine for
      treatment of neuropathic pain in future.

PMID- 19860228
TI  - [Allergic reaction during anesthesia: two case reports].
AB  - We experienced two cases of serious and potentially life-threatening allergic
      reactions. The first patient was a 28-year-old male patient scheduled for surgery
      for cerebral arteriovenous malformations and another patient was a 66-year-old
      male patient scheduled for hepatic resection. After uneventful anesthetic
      induction, anesthesia was maintained with sevoflurane, air and oxygen. Both
      patients developed allergic reactions characterized by cardiovascular failure
      during anesthesia. Resuscitative treatment included rapid fluid infusion,
      administration of adrenaline and steroid. Both patients were successfully
      resuscitated without any lasting sequelae. The causative agent in one of these
      cases was probably a prophylactically used antibiotic, while that of the other
      case was a reaction to latex. Both patients showed elevated histamine and
      tryptase concentrations in blood samples. Recently, the incidence of allergic
      reactions to antibiotics and latex during anesthesia is increasing.
      Anesthesiologists should, therefore, be aware of the possibility of allergic
      reactions to all drugs and substances, especially to latex, during the
      perioperative period.

PMID- 19860229
TI  - [Epidural anesthesia for five caesarian sections in patients with placenta previa
      percreta combined with placenta accreta].
AB  - We gave anesthesia for five cases of caesarian section in patients with placenta
      previa percreta combined with placenta accreta. Five caesarian sections were
      performed under epidural anesthesia and placentae remained in the uterus. After
      surgery, they were transferred to the angiography room and received uterine
      arterial embolization (UAE). They were given the diagnosis of the placenta
      accreta. However, during anesthesia in patients with placenta accreta, incomplete
      separation of the placenta causes atonic bleeding. And, uncleanliness of the
      abrasive degree may lead to difficulty in a prediction of bleeding, and control
      of hemodynamics is difficult. In the caesarian section of the placenta accreta,
      UAE prevents excessive bleeding during the operation and FloTrac monitor makes it
      easy to control hemodynamics.

PMID- 19860230
TI  - [Effects of anesthetic agents on seizure duration and hemodynamics in
      electroconvulsive therapy].
AB  - BACKGROUND: Thiopental and suxamethonium have been recommended as anesthetic
      agents for electroconvulsive therapy (ECT). We hypothesize that propofol and
      vecuronium can also be used and superior to thiopental and suxamethonium in
      seizure duration and hemodynamics. METHODS: We made couples of anesthetic and
      muscle relaxant with these anesthetic agents and obtained four different
      combinations. We evaluated 10 patients with cross-over design, undergoing first
      four sequential ECTs using these four combinations in random turn. Total 40 ECTs
      were divided to four groups and compared with each other in seizure duration,
      blood pressure, and pulse rate. Group TS: thiopental (2 mg x kg(-1)) and
      suxamethonium (1.2 mg x kg(-1)), group PS: propofol (0.75 mg x kg(-1) and
      suxamethonium (1.2 mg x kg(-1)), group TV thiopental (2 mg x kg(-1)) and
      vecuronium (0.07 mg x kg(-1)), group PV: propofol (0.75 mg x kg-1) and vecuronium
      (0.07 mg x kg(-1)). Seizure duration was measured by EEG engineer to whom
      anesthetic agents were unknown. We measured blood pressure and heart rate before
      anesthetic induction, pre-ictal, post-ictal, and every minute for ten minutes
      thereafter. Wilcoxon signed-rank test was used as statistic measures. RESULTS: In
      between-group comparison of dynamics, there was no significant difference in
      these four groups. In seizure duration there was no significant difference
      between thiopental and propofol. Vecuronium (group TV: 27.0 +/- 24.6s, group PV:
      17.5 +/-15.1s) shortened the seizure duration in comparison with suxamethonium
      (group TS: 43.0 +/-25.9s, group PS: 39.2 +/- 28.9s). CONCLUSIONS: Rocuronium,
      which will be used for ECT in future, is needed to be studied in suxamethonium
      controlled design.

PMID- 19860231
TI  - [Suspected case of peripartum cardiomyopathy developed during elective cesarean
      section].
AB  - A 35-year-old primigravida with twin gestation was admitted for elective cesarean
      section. She had no preoperative systemic diseases including heart disease. At 37
      weeks of gestation, elective cesarean section was performed under combined spinal
      epidural anesthesia. Anesthetic course was uneventful until the delivery when the
      patient started to cough and complained of dyspnea. At the same time, Spo2
      started to decline to reach 95% despite the oxygen supplement. Pleural effusion
      was observed on the chest X-ray on postoperative day 2. An echocardiography
      showed diffuse hypokinesis of the left ventricle with ejection fraction (EF) of
      36%. Peripartum cardiomyopathy was strongly suspected. Symptoms of heart failure
      were alleviated by water restriction and furosemide by the 9th POD. The EF
      increased to 50% on the 15th POD.

PMID- 19860232
TI  - [Difficult respiratory management in a patient with bilateral giant bullae].
AB  - We report a case of bilateral giant bullae in a patient with multiple traumas. He
      had his arm amputated at the shoulder because of a machine accident and admitted
      to our hospital. Chest X-ray showed right-sided pneumothorax with bilateral giant
      bullae. Trimming of the stump was performed immediately after the placement of a
      right chest tube. He gradually developed hypoxia and hypercapnia with acidemia
      during the operation because of atelectasis due to sputum. Postoperatively,
      enlargement of right giant bulla led to frequent respiratory failure and he
      received a bilateral bullectomy through a median sternotomy 3 weeks after the
      accident. It was difficult to ventilate him due to air leak from the bilateral
      bulla and SpO2 dropped to below 70% with 100% oxygen. We continued the operation
      with standby extracorporeal membrane oxygenator (ECMO). Although the operation
      was finished without ECMO finally, ECMO had better been kept ready during
      anethesia with giant bullae when life threatening complication may occur at any
      point.

PMID- 19860233
TI  - [Difficult tracheal intubation using airway scope in a pediatric patient with
      Hunter syndrome].
AB  - Hunter syndrome, manifested by mucopolysaccharidosis II (MPS II), is a hereditary
      disorder caused by accumulation of glycosaminoglycans. An important issue in
      regard to anesthesia in affected individuals is airway management, because of
      gargoylism. An 8-year-old boy with MPS II was scheduled for adenotonsillectomy.
      We performed slow induction with sevoflurane, then utilized an Airway Scope (AWS;
      HOYA Corporation Tokyo, Japan), which enables operators to observe tube passage
      through the vocal cords with an LCD monitor, for tracheal intubation, because
      intubation guided by a fiberoptic bronchoscopy (FOB) was considered to be risky
      for glottic damage. Attempted tracheal intubations with the AWS alone and in
      combination with an FOB inserted through the tracheal tube failed, even though a
      clear image of the glottis was obtained. Finally, we inserted a stylet into the
      tracheal tube attached to the blade of the AWS and successful tracheal intubation
      was accomplished. The operation was completed uneventfully and the patient
      entered the ICU with his trachea intubated, because of pharyngeal and laryngeal
      edema. Although useful for difficult airway management, tracheal intubation with
      the AWS may be difficult when used in patients with a narrow oral cavity or small
      tracheal tube.

PMID- 19860234
TI  - [Two cases of postintubation granuloma of the larynx].
AB  - We herein report two cases with postintubation granuloma of the larynx. Under
      general anesthesia, a 72-year-old man underwent off-pump coronary artery bypass
      grafting and a 67-year-old woman underwent AVR, MVR, and TVP. Both patients
      became unable to breathe for more than one month after extubation, and a
      granuloma of the larynx was found which thereafter disappeared with conservative
      therapy in both cases. We found that the two cases had following four points in
      common. Namely, they had both undergone cardiac operations for a low cardiac
      output, they were both intubated for over 96 hours, a Hi-Lo Evac tube was used
      for both cases, and finally, laryngeal glanuloma were observed to develop on the
      membranous wall of the trachea. We concluded that suctioning above the
      endotracheal tube cuff was the cause of postintubation granuloma of the larynx.
      We should keep in mind the fact that postintubation granuloma of the larynx might
      develop several months after extubation, and careful airway manipulation both
      during and after the operation is thus needed to avoid this potential
      complication.

PMID- 19860235
TI  - [Perioperative management of a patient with Parkinson's disease with intravenous
      infusion of levodopa].
AB  - Parkinson's disease is a disorder of the extrapyramidal system resulting from the
      deficiency of dopamine in the basal ganglia. We experienced the perioperative
      management of a patient with Parkinson's disease with intravenous infusion of
      levodopa, precursor of which is dopamine. A 73-year-old woman with Parkinson's
      tremor in her bilateral fingers of Hoehn and Yahr stage II was scheduled for
      repair of bladder prolapse under general anesthesia. Antiparkinson drug
      levodopa/dopa decarboxylase inhibitor (carbidopa) 400 mg per day had been
      administered orally to control her bilateral tremor. Three hours before the
      operation, oral medication including levodopa/carbidopa 100 mg was withdrawn, and
      intravenous infusion of levodopa 100mg was started. Without any premedication,
      anesthesia was induced with intravenous infusion of propofol, fentanyl, and
      vecuronium, and tracheal intubation was facilitated. Anesthesia was maintained
      with inhalation of air, oxygen, and sevoflurane, and intravenous infusion of
      fentanyl. After emergence, we found no neurological disorders excluding her
      tremor. Levodopa/carbidopa 100 mg was readministered orally four hours after the
      operation and total of 300 mg had been administered orally on the operative day.
      Levodopa/carbidopa 400 mg per day had been administered orally after the first
      operative day. She did not show deterioration of her symptom of Parkinson's
      disease, and develop any complications during the perioperative period. We need
      to manage Parkinson's disease with intravenous infusion of levodopa during the
      perioperative period, taking care of the symptom of Parkinson's disease and the
      occurrence of complications.

PMID- 19860236
TI  - [Case of paroxysmal atrial fibrillation after general anesthesia caused by
      undiagnosed and untreated hyperthyroidism].
AB  - A 21-year-old man was scheduled to undergo posterior cruciate ligament
      reconstruction under arthroscopic control. The patient did not have a previous
      history of thyroid disease. Low blood cholesterol was revealed in the laboratory
      data. On arriving at the operating room, he showed sinus tachycardia of 130 beats
      x min(-1). Anesthesia was induced with remifentanil and propofol intravenously
      followed by sevoflurane inhalation, and maintained with remifentanil at a rate of
      0.3 microg x kg(-1) x min(-1) and 2% sevoflurane. Heart rate was stable around 70
      90 beats x min(-1) during the operation. After remifentanil and sevoflurane were
      discontinued following surgery, his heart rate increased and paroxysmal atrial
      fibrillation occurred. Although verapamil was administered intravenously, atrial
      fibrillation and tachycardia persisted. Further investigations revealed an
      elevated serum free thyroxin level and suppressed thyroid-stimulating hormone
      (TSH). Serum TSH receptor antibody concentration was elevated. Upon postoperative
      examination, goiter and the protuberance of the eyes were noticed. We conclude
      that he was suffering from Basedow disease. Although he had no subjective
      symptoms in the preoperative period, the possibility of hyperthyroidism should
      have been predicted from the laboratory data such as hypolipidemia and by
      conducting a careful medical examination. It seems that remifentanil suppresses
      sympathetic activity, and is useful for patients with hyperthyroidism.

PMID- 19860237
TI  - [Pain management using patient controlled epidural analgesia for transient
      osteoporosis of the hip in pregnancy].
AB  - We report the case of a 37-year-old woman who developed severe pain in bilateral
      legs and hip in the eighth month of pregnancy. She was diagnosed as transient
      osteoporosis of the hip in pregnancy by the MRI findings. NSAID is
      contraindicated for late pregnancy, and we selected epidural analgesia for the
      pain management of this case. Patient controlled epidural analgesia was effective
      and no complication occurred in both patient and baby. After delivery, diclofenac
      sodium was administered for three weeks. Complete clinical improvement was
      observed in the seventh month after delivery.

PMID- 19860238
TI  - [Patient scheduled for ligation of the contralateral internal jugular vein and
      its reconstruction following unilateral radical neck dissection].
AB  - A 76-year-old man who had previously undergone unilateral radical neck dissection
      (RND) was scheduled for contralateral radical neck dissection and reconstruction
      of the internal jugular vein (IJV) with the saphenous vein due to local
      recurrence of thyroid carcinoma infiltrating the IJV Reconstruction of the IJV
      was not necessary, however, because the preserved IJV was large enough to drain
      venous return after partial resection of the tumor-infiltrated part of the IJV.
      Reports of anesthetic management for bilateral RND are very rare. In this report,
      we discussed anesthetic management of bilateral RND including physiological
      changes and complications after bilateral IJV ligation and monitoring methods for
      disturbances of cerebral venous circulation.

PMID- 19860239
TI  - [Pitfall in intraoperative electrolyte management for a patient with
      pseudohyperkalemia caused by thrombocytosis].
AB  - An 81-year-old woman was scheduled for gastrectomy due to advanced gastric
      cancer. Preoperative serum potassium concentration was 6.5 mEq x l(-1), and the
      operation was postponed. Renal function was normal and hematopathy was denied
      after bone marrow biopsy. But thrombocyte was 130.5 x 10(4) x mm(-3). Plasma
      potassium concentration was within normal ranges, and she was diagnosed as
      pseudohyperkalemia caused by thrombocytosis. Difference between serum and plasma
      potassium concentrations was more than 1 mEq x l(-1) throughout the surgery. We
      should take a blood plasma sample in patients with hyperkalemia combined with
      thrombosis, when renal function was within normal ranges and hemolysis was
      denied.

PMID- 19860240
TI  - [Successful management with remifentanil of tracheal stent insertion keeping
      spontaneous breathing in a patient with severe respiratory insufficiency].
AB  - We report that spontaneous breathing under total intravenous anesthesia by 0.1
      microg x kg(-1) x hr(-1) of remifentanil and 3 mg x kg(-1) x hr(-1) of propoforl
      can be maintained during the surgery for tracheobronchial stent insertion in a
      man with severe trachea stenosis. Remifentanil is an ultra-short acting narcotic,
      and is excellent for relieving pain maintaining stable hemodynamics. As this drug
      is used at a low dose, it is suitable for this case which requires a short time
      of operation, minimally invasive surgery, prevention of moving, and the
      spontaneous breathing. We could achieve steady respiratory and hemodynamic
      control.

PMID- 19860241
TI  - [Case of inguinal hernia repair with transversus abdominis plane block and rectus
      sheath block].
AB  - Transversus abdominis plane block is effective for lower abdominal and inguinal
      operations, and rectus sheath block is effective for abdominal operations.
      Recently, ultrasound guided nerve block has been employed, and these techniques
      can be performed with ultrasound scanning. An 82-year-old man with severe
      coronary failure and chronic obstructive pulmonary disease was scheduled for
      inguinal hernia repair. We did not want to select general anesthesia for him, and
      performed rectus sheath block and transversus abdominis plane block. We achieved
      good anesthetic management using two peripheral blocks under ultrasound scanning.

PMID- 19860242
TI  - [Combined spinal-epidural anesthesia for abdominal surgery in a patient with
      chronic obstructive pulmonary disease].
AB  - A 69-year-old man (150 cm, 57 kg)who had been diagnosed as having COPD, was
      admitted to our hospital because of abdominal pain and drowsiness. He was
      diagnosed as CO2 narcosis and perforation of appendix. When he recovered from CO2
      narcosis, he was scheduled for elective ilectomy. Because his pulmonary function
      was impaired, combined spinal and epidural anesthesia was selected. With the
      patient in the right lateral position, an epidural catheter was inserted at T12
      L1 interspace, and spinal anesthesia was performed at L3-4 interspace with 0.5%
      isobaric bupivacaine 4 ml. When the patient was positioned laterally, SpO2
      decreased from 82% to 77%. After completion of injection, the patient was
      returned to the supine position, and SpO2 immediately recovered. Spinal block
      level was not satisfactory, and fentanyl 0.1 mg and 2% mepivacaine 4 ml were
      administered through epidural catheter to achieve a T4 level of block. Because
      severe intraperitoneal inflammation was observed, ilectomy was changed to
      drainage of intra-abdominal abscess. The patient did not complain of dyspnea,
      pain, or nausea, intraoperatively. SpO2 was 85-93% with O2 inhalation at 1l x
      min(-1) during the operation. Post-operative course was uneventful. Although
      lateral position is popular in performing epidural and spinal anesthesia, sitting
      position could be suitable for this patient. Decrease in SpO2 may have occurred
      due to ventilation-perfusion mismatch. Since combined spinal and epidural
      anesthesia can preserve spontaneous respiration and it is possible to titrate
      anesthetic level, it would be preferable for abdominal surgery in patients with
      COPD.

PMID- 19860243
TI  - [Anesthetic management for pancreaticoduodenectomy in a patient with Charcot
      Marie-Tooth disease and liver cirrhosis].
AB  - A 68-year-old man was scheduled for pancreaticoduodenectomy under general
      anesthesia. He was suffering from Charcot-Marie-Tooth disease (CMTD) for 34
      years, and complicated with liver cirrhosis. Anesthesia was induced with propofol
      and fentanyl, and maintained with oxygen-air-sevoflurane and remifentanil.
      Epidural block was not used because the patient had coagulation abnormality and
      thrombocytopia. Rocuronium was injected intravenously for tracheal intubation,
      supplemented as required using an electrical nerve stimulator. The longer
      duration of action of rocuronium was observed in this case because the patient
      was complicated with CMTD and liver cirrhosis. We suggest that monitoring
      neuromuscular function may be necessary to detect subtle residual neuromuscular
      blockade when rocuronium is used in a patient with CMTD and liver dysfunction.

PMID- 19860244
TI  - [Introduction of computerized anesthesia-recording systems and construction of
      comprehensive medical information network for patients undergoing surgery in the
      University of Tokyo Hospital].
AB  - The computerized anesthesia-recording systems are expensive and the introduction
      of the systems takes time and requires huge effort. Generally speaking, the
      efficacy of the computerized anesthesia-recording systems on the anesthetic
      managements is focused on the ability to automatically input data from the
      monitors to the anesthetic records, and tends to be underestimated. However, once
      the computerized anesthesia-recording systems are integrated into the medical
      information network, several features, which definitely contribute to improve the
      quality of the anesthetic management, can be developed; for example, to prevent
      misidentification of patients, to prevent mistakes related to blood transfusion,
      and to protect patients' personal information. Here we describe our experiences
      of the introduction of the computerized anesthesia-recording systems and the
      construction of the comprehensive medical information network for patients
      undergoing surgery in The University of Tokyo Hospital. We also discuss possible
      efficacy of the comprehensive medical information network for patients during
      surgery under anesthetic managements.

PMID- 19860245
TI  - [BONFILS retromolar intubation fiberscope VS styletscope for oro-tracheal
      intubation].
AB  - BACKGROUND: Battery-powered BONFILS Retromolar Intubation Fiberscope (B-scope) is
      a nonflexible fiberscope having the same curvature as the Macintosh laryngoscope.
      Battery-powered StyletScope (S-scope) has a flexible apex whose direction was
      controlled by grasping a handle. We assessed the operational performance of the
      two scopes. METHODS: Fifty patients were randomly allocated in the two groups :25
      patients were in the B group (B-scope) and 25 were S group (S-scope) after
      obtaining written informed consent. We evaluated Mallampati class classification,
      size of tracheal tube, and intubation time. RESULTS: There are no significance
      differences between the two groups in Mallampati class, demographic date and
      intubation time (23 +/-15 sec in B-group and 26 +/-14 sec in S-group). Both
      scopes were good in operational performance. CONCLUSIONS: BONFILS Retromolar
      Intubation Fiberscope and StyletScope are both good in the operational
      performance.

PMID- 19860246
TI  - [A day in the busy obstetric unit from the anesthesiologist point of view,
      experience at the Cleveland clinic; Cleveland, Ohio].
AB  - Cleveland Clinic Labor and Delivery Unit is a syntactical delivery facility and
      comprised of 16 delivery rooms, 3 operating rooms, 3 triage rooms, and 1 recovery
      room that has a capacity of 6 beds, 43 postpartum rooms, 2 nurseries, and 1
      neonatal intensive care unit (NICU). Cleveland Clinic Labor and Delivery Unit
      (LDU) had 3,691 delivery cases in 2007. The ratio of neuraxial analgesia (NA)
      during labor is 84.2% (2,348/ 2,787), using epidural anesthesia or combined
      spinalepidural anesthesia (CSEA). This article introduces the obstetrical (OB)
      anesthesia practice at the Cleveland Clinic and our novel anesthetic regime as
      typical of one typical busy day.

PMID- 19860247
TI  - [Mechanism behind streptococcus toxic shock-like syndrome onset--immune evasion
      and bacterial properties].
AB  - Streptococcal toxic shock-like syndrome (STSS) was firstly reported in 1987 in
      the United States. Japan's first definitive STSS case was reported in 1992, with
      over 500 cases since confirmed. Mortality is extremely high at 40%. Pathological
      findings, bacteria aggregation, and a paucity of polymorphonuclear neutrophils
      (PMN) in the foci of invasive group A streptococcal (GAS) infection suggest that
      host defense disturbance plays an important role in invasive infection onset.
      GAS, clinically isolated from severely invasive, but not from non-invasive,
      infections, could compromise human PMN functions in at least two independent ways
      by inducing necrosis to PMN by enhanced production of pore-forming toxin
      streptolysin O (SLO) and by PMN migration impairment via digesting interleukin-8,
      a PMN attracting chemokine, through increased serine protease ScpC production.
      Expression of these genes was upregulated by a loss of repressive function with
      the csrS gene mutation of the two-component sensor/regulator system.

PMID- 19860248
TI  - [Colony-sweep PCR efficacy in food-borne outbreak associated with six types of
      enterotoxigenic Escherichia coli].
AB  - A box-lunch-associated food-borne outbreak occurred in Tokyo and Chiba Prefecture
      in June 2003 involved six types of enterotoxigenic Escherichia coli (ETEC). Fecal
      specimens from patients were screened for ETEC using colony-sweep polymerase
      chain reaction (PCR). Of the 84 fecal specimens examined, 56 (66.7%) were PCR
      positive, i.e. 35 (41.7%) LT-gene-positive, 21 (25.0%) STp-gene-positive and 11
      (13.1%) STh-gene-positive. Both of toxin-genes, i.e. LT and STp, LT and STh, STh
      and STp were positive in 11 patients. ETEC was isolated in confirmation testing
      from 48 (57.1%) fecal specimens. A single type of ETEC was isolated from 43 fecal
      samples. Serotype and toxin type of the isolates were O25:NM (LT) (21 samples),
      O27:H20 (STp) (12 samples), O148:H28 (STh) (8 samples), O25:NM (STh) (1 sample),
      and O27:7 (STp) (1 sample). Two types of ETEC were isolated from 5 fecal samples,
      i.e. O25:NM (LT) and O27:H20 (STp) (3 samples), O27:H20 (STp) and O148:H28 (STh)
      (1 sample), and O25:NM (LT) and O78:NM (STh) (1 sample).

PMID- 19860249
TI  - [Occurrence of Tsutsugamushi disease infection by Orientia tsutsugamushi,
      Kawasaki serotype, in Yamagata Prefecture, Japan].
AB  - Of 95 Tsutsugamushi disease case occurring in Yamagata prefecture from 1999 to
      2006, four-all women-involved the O. tsutsugamushi Kawasaki serotype. The three
      major symptoms were fever, exanthema, and eschar present from mid-October to
      early November. Serodiagnosis by indirect immunofluoresence assay showed elevated
      IgG and IgM antibody titers against the Kawasaki serotype antigen, with IgM
      higher than IgG. Nested PCR detected 56-kDa DNA in three of the cases. DNA was
      amplified in Kawasaki-specific PCR. Two cases for which sequencing was done using
      nested PCR-amplified DNA showed an identity of 99.8% for the Kawasaki strain
      (Accession number: M63383). These results confirmed the occurrence of
      Tsutsugamushi disease infection involving Kawasaki serotype in Yamagata
      prefecture.

PMID- 19860250
TI  - [Psittacosis outbreak at an avian exhibition].
AB  - Psittacosis outbreak due to Chlamydophila psittaci occurred among staff members
      at an avian exhibition of nearly 1,000 birds in Kobe, Japan, in December 2005.
      Staff members not trained about zoonosis or psittacosis used little protective
      attire such as masks and gloves when caring for their discharges. Two of 67 staff
      members contracted psittacosis pneumonia. Additional two suffered from pneumonia
      and 19 reported symptoms such as fever and cough, although none were diagnosed
      with psittacosis. The roughly 970 birds were kept without quarantine and
      identified by leg bands. Doxycycline administrated in drinking water and food
      failed to eradicate chlamydia, so all birds were captured, identified by leg
      band, and tested for chlamydia by PCR. Six were found to carry large amounts of
      chlamydia. Major outer membrane protein (MOMP) DNA sequence of chlamydia in a
      patient's bronchoalveolar lavage fluid (BALF) was identical to that derived from
      a channel-billed toucan kept in a closed aviary, and staff members may have been
      infected by inhaling excrement while working in the aviary. The MOMP DNA sequence
      was useful in comparing strains. We review the difficulty of diagnosing
      psittacosis and the knowledge and infection control measures required against it.

PMID- 19860251
TI  - [MRSA-related empyema as thoracic surgical site infection].
AB  - The incidence of empyema as a thoracic surgical site infection (SSI) is relating
      low, but empyema related to MRSA poses an unenviable therapeutic challenge. We
      review 3 cases of MRSA-related empyema as SSI seem in the last 10 years, and
      evaluate therapeutic measures. All 3 subjects began being administered vancomycin
      (VCM) systemically once the diagnosis was established. Subject 1 developed MRSA
      related empyema following pulmonary segmentectomy for small-cell lung cancer. The
      subject was treated following a diagnosis of incisional SSI, with delayed
      adequate pleural drainage, resulting in treatment difficulties, but was cured
      without becoming MRSA-negative. Subject 2 developed MRSA-related empyema
      following pulmonary lobectomy for advanced lung cancer associated with
      pneumoconiosis. Following bronchoplasty, a chest tube was placed for long-term
      drainage. The subject did not become MRSA-negative after VCM administration, but
      became so after linezolid treatment, facilitating a cure. Subject 3, who had
      secondary pneumothorax, underwent thoracoscopic partial hepatic resection.
      Intraoperative findings suggested pleural cavity infection, necessitating a
      prophylactic drain, but MRSA-related pyothorax developed. Fibrinolysis with
      urokinase effectively cleared up the poor drainage and the subject was cured
      without becoming MRSA-negative. In conclusion, in controlling MRSA-related
      empyema as SSI noted that: (1) long-term postperative thoracic drain retention
      may lead to retrograde infection; (2) surgical procedures reducing the extent of
      pulmonary resection may effectively prevent pyothorax progression; (3) for poor
      drainage in advanced pyothorax, fibrinolytic therapy is worth attempting before
      thoracoscopic surgery; and (4) the timing for discontinuing anti-MRSA drugs
      should be determined based on the clinical course rather than negative conversion
      of bacteria.

PMID- 19860252
TI  - [Clostridium difficile TOX A/B II TEST evaluation].
AB  - We compared the performance of two commercial toxin detection kits, C. difficile
      toxin A/B (C. difficile TOX A/B II test; TOX A/B II) and C. difficile toxin A
      (Uniquick), for (i) detection using highly purified toxin A solution; (ii) cross
      reactivity using culture supernatants of toxin A-positive and B-positive C.
      difficile, toxin A-negative and B-positive C. difficile, and toxin A-negative and
      B-negative C. difficile strains and other bacteria; and (iii) sensitivity and
      specificity using clinical specimens. Results indicated that TOX A/B II detected
      toxin A at concentrations of 0.35 ng/mL and Uniquick at concentrations of 0.7
      ng/mL. Uniquick performance was specific for detecting toxin A alone, while TOX
      A/B II detected toxin A/B specifically. Kit performance was then evaluated using
      99 fecal specimens--43 specimens from patients with toxin B-positive C. difficile
      and 56 from those without. Sensitivity of TOX A/B II vs Uniquick was 95.3% vs
      76.7%, specificity 98.2% vs 98.2%, positive predictive 97.6% vs 97.1%, and
      negative predictive value 96.5% vs 84.6%. Findings thus indicate that TOX A/B II
      is a more suitable diagnostic aid for CDAD than Uniquick because it correlates
      well with toxin B-positive C. difficile culture results. Stool culture for C.
      difficile is also required, however.

PMID- 19860253
TI  - [EIA-IgG antibody measles prevention level estimated from measles neutralizing,
      particle agglutination and hemagglutination-inhibition antibody titer].
AB  - Measles hemagglutination inhibition (HI) antibody titer, widely used in clinical
      practice to simply and easily determine the measles immunity level has, in recent
      years, been increasingly replaced by measles IgG-antibody titer determined by
      enzyme-immunoassay (EIA). HI antibody titer appears to reflect this protective
      level, because HI measures the antibody against H protein required for the
      measles virus to adhere to host cells. EIA-IgG antibody titer does not correlate
      with the protective level, similar to particle agglutination (PA) titer, because
      EIA measures different antibodies, including those unrelated to measles
      protection. After determining HI, PA, neutralizing test (NT) results, and EIA-IgG
      antibody titer for individual specimens, we compared EIA-IgG antibody titer
      obtained using an EIA-Kit (Denka Seiken) to HI, PA, and NT titer with the
      following results: (1) Subjects with EIA-IgG titer of > or = 12.0 may be
      protected against measles: (2) Subjects with EIA-IgG titer of 4.0 to 8.0 appear
      to be protected insufficiently requiring a booster dose against measles: (3)
      Subjects with EIA-IgG titer of 8.0 to 12.0 may benefit from booster vaccination.

PMID- 19860254
TI  - [Comparison of detection sensitivity in rapid-diagnosis influenza virus kits].
AB  - Rapid-diagnosis kits able to detect influenza A and B virus by
      immunochromatography developed by different manufacturers, while useful in early
      diagnosis, may vary widely in detection sensitivity. We compared sensitivity
      results for eight virus-detection kits in current use--Quick Chaser FluA, B
      (Mizuho Medy), Espline Influenza A & B-N (Fujirebio), Capilia Flu A + B (Nippon
      Beckton Dickinson & Alfesa Pharma), Poctem Influenza A/B (Otsuka Pharma &
      Sysmex), BD Flu Examan (Nippon Beckton Dickinson), Quick Ex-Flu "Seiken" (Denka
      Seiken), Quick Vue Rapid SP Influ (DP Pharma Biomedical), and Rapid Testa FLU
      stick (Daiichi Pure Chemicals)--against influenza virus stocks, contained five
      vaccination strains (one A/H1N1, two A/H3N2, and two B) and six clinical strains
      (two A/H1N1, two A/H3N2, and two B). Minimum detection concentrations giving
      immunologically positive signals in serial dilution and RNA copies in positive
      dilution in real-time reverse transcriptase-polymerase chain reaction (RT-PCR)
      were assayed for all kits and virus stock combinations. RNA log10 copy numbers/mL
      in dilutions within detection limits yielded 5.68-7.02, 6.37-7,17, and 6.5-8.13
      for A/H1N1, A/H3N2, and B. Statistically significant differences in sensitivity
      were observed between some kit combinations. Detection sensitivity tended to be
      relatively higher for influenza A than B virus. This is assumed due to different
      principles in kit methods, such as monoclonal antibodies, specimen-extraction
      conditions, and other unknown factors.

PMID- 19860255
TI  - [Toxoplasmic encephalitis and cytomegaloviral retinitis in a non-AIDS patient
      with chronic renal failure undergoing corticosteroid therapy].
AB  - We report a rare case of toxoplasmic encephalitis in a non-AIDS patient A 62-year
      old man undergoing hemodialysis for seven months and corticosteroid therapy for
      rapidly progressive glomerulonephritis and admitted for generalized convulsions
      was found in cranial magnetic resonance imaging (MRI) to have multiple ring
      enhanced lesions. Antibodies against Toxoplasma gondii, and in Sabin-Feldman dye
      test were extremely high, yielding a diagnosis of toxoplasmic encephalitis. He
      was also diagnosed as having cytomegaloviral retinitis. Anti-HIV antibody was
      negative. Treatment with pyrimethamine and clindamycin was effective and
      intracerebral lesions disappeared. Physicians encounting a similar situation
      should consider toxoplasmic encephalitis as a differential diagnosis, even in non
      HIV patients, and implement confirmational examination.

PMID- 19860256
TI  - [A case of disseminated nocardiosis followed by pneumocystis pneumonia in a
      patient prescribed corticosteroid and cyclosporin A and having elevated blood (1-
      >3)-beta-D-glucan].
AB  - A 78-year-old man administered prednisolone and cyclosporin A for bullous
      pemphigoid and found in computed tomography (CT) to have a left-lung nodule was
      suspected of having a fungal infection due to elevated blood (1-->3)-beta-D
      glucan. Despite empirical antifungal therapy, however, the nodule grew, followed
      by new nodules in both lungs. Disseminated nocardiosis was eventually diagnosed
      based on sputum, blood, and skin cultures growing Nocardia sp. Antinocardial
      treatment with imipenem/cilastatin and amikacin was started. The patient then
      developed pneumocystis pneumonia for which pentamidine was added. He had
      recovered completely when antimicrobial therapy was completed. A wide variety of
      microorganisms may infect patients with impaired cellular immunity,
      simultaneously involving multiple organisms in some cases. Definitive
      microbiological diagnosis with culture or biopsy specimens is therefore crucial
      for appropriate management.

PMID- 19860257
TI  - [A case of Streptococcus suis endocarditis, probably bovine-transmitted,
      complicated by pulmonary embolism and spondylitis].
AB  - Streptococcus suis, a major global porcine pathogen, is an emerging zoonosis in
      Southeast Asia that triggered a 2005 outbreak in China. S. suis causes
      meningitis, sepsis, and endocarditis in both pigs and humans and involves
      significant mortality. We report the case of a previously healthy 50-year-old
      dairy farmer who developed S. suis type 2 endocarditis complicated by pulmonary
      embolism and spondylitis. He experienced a high fever, chills, fatigue, and
      worsening low back pain in the 6 weeks prior to admission. On physical
      examination, he had lumbar spine tenderness and weakness of the left leg. Blood
      culture identified penicillin-sensitive S. suis type 2. Echocardiography showed
      vegetation on the tricuspid valve, and magnetic resonance imaging (MRI) showed
      signs of spondylitis. The man reported sudden chest pain several days after
      admission, which computed tomography (CT) showed what was diagnosed as a septic
      pulmonary embolism. He was treated with penicillin G for 4 weeks and gentamicin
      for the first 2 weeks, followed by 2 weeks of oral amoxicillin, after which his
      symptoms gradually improved. The infection source was probably his dairy herd,
      since calves often bit his fingers while feeding and S. suis was found in their
      oral mucus. Over 400 cases of human S. suis infection have been reported
      globally, but this is, to our knowledge, the first known case of bovine
      transmission. All of Japan's 8 other cases involved occupational swine exposure,
      5 of whom had injuries to their fingers. This emerging situation should be made
      known to all possibly involved in unprotected direct contact with swine and
      cattle, particularly when the skin could be compromised by cuts or abrasions.

PMID- 19860258
TI  - [Antibiotic-associated diarrhea due to Clostridium perfringens].
AB  - A 40-year-old man undergoing allo-hematopoietic stem cell transplantation for
      chronic myelogenous leukemia and developing diarrhea was administered
      prophylactic antibiotics including levofloxacin, fluconazole, cotrimoxazole, and
      vancomycin. Stool specimens were positive for toxin A in enzyme immunoassay but
      negative for toxin B in cell culture assay with a neutralization test, indicating
      that toxin A detection was false-positive. Stool culture yielded enterotoxin
      producing Clostridium perfringens, not Clostridium difficile. Polymerase chain
      reaction (PCR) detected the gene encoding C. perfringens enterotoxin in DNA
      extracted from stool specimens, but not the toxin B gene. Laboratory tests for
      enterotoxic C. perfingens may therefore be necessary for diagnosing antibiotic
      associated diarrhea when culture for C. difficile is negative.

PMID- 19860259
TI  - [A case of bacteremia and suppurative vertebral osteomyelitis/discitis due to
      Shewanella algae occurring after raw-fish consumption].
AB  - Shewanella algae is an aquatic gram-negative bacterium, rarely recovered from
      human clinical samples. Case reports of human Shewanella infection are, however,
      slowly increasing, and a Shewanella infection outbreak was reported at a South
      Korean hospital. We report the case of an 89-year-old man admitted for back pain
      and fever after eating raw marine fish. Sulbactam/cefoperazone was started under
      a tentative diagnosis of gall bladder inflammation with gallstones based on
      ultrasonographic findings. His persistent back pain, however, necessitated
      vertebral magnetic resonance imaging (MRI), which showed thoracic vertebral
      osteomyelitis and discitis. Two sets of blood culture on admission yielded a gram
      negative bacillus identified as "Shewanella putrefaciens" by automated
      identification. Ceftriaxone administration for 3 weeks followed by oral
      levofloxcin for 5 weeks cured the vertebral osteomyelitis and discitis. 16S rRNA
      sequence analysis showed that "S. putrefacien" was, in fact, S. algae-incorrectly
      detected because semi-automated and automated identification did not include S.
      algae in their database. It should thus be kept in mind that consuming raw-fish
      may cause Shewanella bacteremia and osteomyelitis in patients with hepatobiliary
      disease and that genetic analysis is required to precisely determine the
      occurrence of Shewanella spp.

PMID- 19860260
TI  - [A case of cat-scratch-induced Pasteurella multocida infection presenting with
      disseminated intravascular coagulation and acute renal failure].
AB  - Domestic animals are the main reservoirs of Pasteurella species for human
      zoonosis due to bites and scratches. Pasterurella multocida may cause serious
      soft-tissue infection and, less commonly, sepsis or septic shock, particularly in
      insufficient initial therapy and an immunocompromised host. We report a case of
      cat-scratch-induced P. multocida infection, presenting with disseminated
      intravascular coagulation and acute renal failure. A febrile 83-year-old woman
      with consciousness disturbance and a subcutaneous left-foot abscess due to a
      scratch from a pet cat. She was successfully treated with antibiotic piperacillin
      and clindamycin therapy and aggressive wound drainage.

PMID- 19860262
TI  - [Comparison of norovirus genotypes by real time PCR (genogroup II)].

PMID- 19860261
TI  - [A case of ventriculo-atrial shunt infection diagnosed by blood culture and
      serial cerebrospinal fluid protein measurement].
AB  - Ventriculo-atrial shunt infection (VASI) may lead to sepsis and/or nephritis,
      making early diagnosis critical. VASI is usually diagnosed by cerebrospinal fluid
      culture conducted after ventricular puncture or shunt removal, both of which are
      invasive. Non-invasive attempts at diagnosis, however, present a nonspecific
      clinical picture unless shunt dysfunction is present. A 57-year-old woman treated
      with ventriculo-atrial shunt 10 months earlier due to hydrocephalus following
      subarachnoid hemorrhage developed a fever but evidenced no infected organs in
      general examination although Staphylococcus epidermidis was isolated several
      times upon blood culture. Enhanced brain computed tomography (CT) showed neither
      abnormal findings nor changes in ventricular size and no shunt dysfunction was
      demonstrated clinically. In cerebrospinal fluid examination, the protein level
      was 137 mg/dL and cell count and bacteriological findings were normal. 10 days
      later, however, the cell count and bacteriological findings were normal but
      protein was 180 mg/dL. The cerebrospinal fluid protein increase indicated VASI,
      and the shunt was removed. The woman's fever was immediately alleviated and
      Staphylococcus epidermidis was detected in the cerebrospinal fluid culture of the
      specimen from the shunt tip and its periphery. Blood culture is useful for
      identifying bacterial etiology of VASI if neither cerebrospinal fluid cell count
      increases nor abnormal bacteriological findings are observed, provided that
      cerebrospinal fluid protein increase are observed in serial measurement.

PMID- 19860263
TI  - [The relation between nutritional state of tuberculous patients admitted in
      tuberculous ward and their outcome at the time of discharge].
AB  - OBJECTIVES: To investigate the relation between nutritional state of tuberculous
      patients admitted in tuberculous ward and their outcome at the time of discharge.
      PATIENTS AND METHODS: We retrospectively investigated BMI, peripheral blood
      lymphocyte count, serum albumin concentration, and induration size of PPD skin
      test at the time of admission from their clinical charts of all 174 tuberculous
      patients newly admitted in NHO Omuta National Hospital during the period from
      2000 to 2002, and based on these indices, the nutritional state of tuberculous
      patients was divided into severely impaired, moderately impaired, and mildly
      impaired or normal. The relation between nutritional state on admission and the
      outcome at the time of discharge was examined. RESULTS: The worse the nutritional
      state on admission, the higher the rate of death from all causes and
      tuberculosis, and the higher the average age and the duration of hospitalization.
      CONCLUSIONS: The assessment method of nutritional state reported in our study is
      easily applicable to every tuberculous patients admitted in tuberculous ward, and
      the outcome of tuberculous patients at the time of discharge could be expected,
      based on the nutritional state assessed with this method. Prospective study is
      needed to ascertain the validity of results obtained in the present study.

PMID- 19860264
TI  - [Relapse rate of tuberculosis treated with standard regimen of chemotherapy].
AB  - BACKGROUND: Japanese standard of Tuberculosis treatment indicates that six months
      treatment with isoniazid, rifampicin and pyrazinamide can be extended to nine
      months under certain conditions such as diabetics. We have little information on
      the validity of the duration of treatment as yet. METHOD: The treatment result of
      isoniazid and rifampicin susceptible new TB cases treated with the regimen
      including isoniazid, rifampicin and pyrazinamide were analyzed with the
      categorization of duration of treatment. Risk factors of bacteriological relapse
      were evaluated. RESULTS: Among 839 cases treated at the facilities of Ryoken
      members in 2005, 27 cases relapsed bacteriologically. The rate of relapse (3%)
      was the same between those that were treated for six months and those treated for
      nine months. Diabetic cases, immuno-compromised cases and extensive cavitary
      cases showed higher risk of relapse if they were treated with six months regimen
      than in cases treated with nine months regimen. Those that were culture positive
      even after 2 months of treatment showed high rate (6-7%) of relapse if they were
      treated with six to nine months regimen but no relapse was observed if they were
      treated for >40 weeks or if they were treated for more than 6 months after
      conversion to negative culture. CONCLUSIONS: Our results did not indicate that
      Japanese standard of TB treatment should be changed regarding extension of
      treatment for diabetics and serious cases. Those who remained culture positive
      after 2 months of treatment should be treated >9 months and/or at least 6 months
      after culture negative conversion.

PMID- 19860265
TI  - [Clinical evaluation of acid-fast smear examination with light emitting diode
      fluorescent microscopy].
AB  - OBJECTIVE: Fluorescent smear microscopy is one of the recommended methods to
      detect highly infectious tuberculosis (TB) patients. Recently, fluorescent
      microscopy using a light emitting diode (LED) as a light source has been
      developed and introduced. The objective of this study is to evaluate the
      efficiency of LED fluorescent microscopy. METHOD: The clinical specimens were
      collected from TB suspects and follow-up patients of mycobacteriosis in Double
      Barred Cross Hospital through Sept. to Oct. in 2008. The specimens were subjected
      to the ordinary decontamination/concentration process, and the sediments were
      smeared and stained with auramine O. The slides were examined using an ordinary
      mercury vapour lamp and a LED fluorescent microscope by at least two laboratory
      technologists independently. If there was a discrepancy between the first and
      second reader, the third reader (umpire) judged the result. The treated specimens
      were also cultured using BACTEC MGIT or 2% Kudoh medium. The smear and culture
      results were compared with the results of LED fluorescent microscopy. RESULTS: A
      total of 1324 specimens, including 1192 sputa and 23 pleural fluid, were
      collected from TB suspects and patients. The overall agreement, smear positive
      versus smear negative, occurred in 1,300 of 1,324 specimens (98.2%). Among the
      mutually positive readings, the agreement on grading was 256 out of 334 (76.6%),
      and disagreement beyond two grades was observed only in 3 specimens. The smear
      positive/culture positive rates were not statistically different between two
      smear methods. DISCUSSION: The overall efficiency of LED fluorescent microscopy
      was similar to that of ordinary fluorescent microscopy with a mercury vapour
      lamp. The LED costs less than mercury vapour lamp, and has a usable life of more
      than 40,000 h. It does not require either a dark room for observation, or a long
      waiting time for stabilization. It was expected that the LED fluorescent
      microscopy would be utilized widely for the efficient detection of acid-fast
      bacilli in clinical practices.

PMID- 19860266
TI  - [Cross-resistance between rifampicin and rifabutin among multi-drug resistant
      Mycobacterium tuberculosis strains].
AB  - OBJECTIVE: To compare the susceptibility of rifampicin (RFP) and rifabutin (RBT)
      against multi-drug resistant Mycobacterium tuberculosis (MDR-TB). METHOD: A total
      of 44 confirmed MDR-TB strains collected by Ryoken consortium and 97 susceptible
      M. tuberculosis strains were tested for the susceptibility to RBT, following CLSI
      M24-A laboratory standard. The core 81bp region of rpoB gene was sequenced for
      MDR-TB strains, and the mutations were defined. RESULTS: Among the 44 MDR-TB
      strains tested, 12 strains were susceptible to RBT. The genetic alterations were
      identified in 43 of 44 MDR-TB strains. The RBT susceptible strains had
      alterations mainly at codons 506-508, 511, 512, and 516. The mutation at codons
      526 and 531 closely related to RBT resistance with two exceptions. The overall
      cross-resistance between RFP and RBT was 72.7%. DISCUSSION: RBT will be a
      candidate drug for the treatment of MDR-TB. In this study, approximately 27% of
      MDR-TB in Japan had susceptibility to RBT. However, the drug susceptibility
      testing for RBT is not easy at general microbiology laboratory considering the
      preparation of medium and laboratory facilities. It is also difficult to transfer
      confirmed MDR-TB strains to one place to another for testing legally. The
      mutations at codons 526 and 531 in rpoB are closely related to RBT resistance and
      will be useful to predict its susceptibility.

PMID- 19860267
TI  - [Cepharanthin effect on radiation-induced xerostomia and taste disorder in
      patients with head and neck cancer].
AB  - In evaluating the effect of cepharanthin on xerostomia and taste disorder in 40
      patients undergoing radiotherapy for head and neck cancer, we administered
      cepharanthin intravenously during chemoradiotherapy to 22 patients, with 18
      others as a control group. Cepharanthin did not significantly affect salivary
      secretion during and after chemoradiotherapy, although taste disorder and oral
      discomfort were alleviated. Cepharanthin may thus be effective in maintaining the
      quality of life of patients with head and neck cancer.

PMID- 19860268
TI  - [Ramsay Hunt syndrome with cranial polyneuropathy involving cranial nerves VII,
      VIII, IX, and X].
AB  - In addition to facial and vestibular nerve paralysis, patients with Ramsay Hunt
      syndrome may also show glossopharyngeal, vagal, and hypoglossal nerve paralysis.
      We report a case of Ramsay Hunt syndrome with cranial polyneuropathy including
      cranial nerves VII, VIII, IX, and X. A 58-year-old rheumatic woman suffering from
      vertigo, right earache, and sore throat suffered right-side facial palsy,
      hoarseness, and swallowing difficulty on day 5. Admitted on day 6, she was
      treated with antiviral medication and steroids. Although vertigo, facial palsy,
      and hearing loss gradually improved, hoarseness required over three months to
      recover. Of the 33 patients with Ramsay Hunt syndrome we have seen, 9 (27%) had
      cranial polyneuropathy, including cranial nerves IX and X in 4 years. Of these,
      9% involved total paralysis of nerves IX and X. Physical symptoms of those with
      polyneuropathy, especially vagal nerve palsy, tended to worsen, making it
      important to observe other cranial nerve signs, such as for IX and X carefully,
      in addition to VII and VIII.

PMID- 19860269
TI  - [Upper airway obstruction caused by a floppy epiglottis--report of two cases of
      amyotrophic lateral sclerosis (ALS)].
AB  - The motor system is extensively affected in amyotrophic lateral sclerosis (ALS).
      Rapid disease progression almost certainly ensures that about half of thsese
      cases will experience respiratory muscle paralysis to breathe within about five
      years. We report two cases of ALS involving upper airway obstruction. Fiberoptic
      laryngoscopy showed floppy epiglottis, tilted posteriorly and horizontally and
      impacting against the posterior pharyngeal wall during inspiration. Several
      months later, airway obstruction grew exceedingly worse, and the tilted
      epiglottis did not return to its vertical resting position. Tracheostomy was
      conducted during this period. We found that laryngoscopy may be useful in the
      evaluation of upper airway obstruction, and it may be safer to avoid continuous
      positive airway pressure.

PMID- 19860270
TI  - Mucinous cystadenoma of the ovary presenting as unilateral lower extremity edema.
AB  - INTRODUCTION: Mucinous cystadenomas of the ovary are known for their potential to
      grow to massive proportions and are often incidentally diagnosed. They are
      typically benign tumors accounting for 15% of ovarian neoplasms and up to 80% of
      all mucinous tumors. CASE REPORT: We report a 50-year-old, morbidly obese female
      admitted with left lower extremity edema who was incidentally found to have a
      massive, benign, mucinous cystadenoma of the ovary. The tumor was managed by
      laparotomy, cystectomy, and right salpingo-oophorectomy. Pathology revealed a
      benign cyst. CONCLUSION: The clinically silent course of these large, benign
      tumors can have unique presentations.

PMID- 19860271
TI  - Thymoma developing 30 years after mantle radiation for Hodgkin's lymphoma.
AB  - Treatment-related malignancies are widely reported in the medical literature.
      They are usually chemotherapy-related leukemias or radiation-induced solid
      tumors. Here we present a case of a 47-year-old woman treated with mantle
      radiation for Hodgkin's lymphoma who later developed a thymoma in the setting of
      a venous thrombosis. A review of the literature including surveillance
      recommendations for secondary malignancies will be discussed.

PMID- 19860272
TI  - Status epilepticus: a review of current pharmacologic treatments.

PMID- 19860273
TI  - A medical odyssey to Camaguey, Cuba.

PMID- 19860275
TI  - Improving medical grand rounds: barriers to change.
AB  - BACKGROUND: Grand rounds programs may not be consistently structured to bring
      benefit from evidence-based practices of effective continuing medical education.
      In order to make improvements in this common educational forum, educational
      leaders need to consider and possibly overcome some barriers as perceived by
      planners, presenters, and participants. Research on perceived barriers to
      improving grand rounds is lacking. METHODS: Using an instrumental case-study
      approach, the investigators sought to describe perceived barriers to improving a
      Medical Grand Rounds program held at an academic medical center in the Northeast.
      Perceived barriers were identified by program planners, presenters, and
      participants. The study used qualitative data collected from each group via key
      informant interviews and a focus group to assess barriers in relation to five
      evidence-based practices: needs assessment, multifaceted intervention strategy,
      sequencing, interaction, and commitment to change. The study used an intensive,
      inductive approach to analyze data to determine barrier themes from each group.
      RESULTS: Studied during 2007, program constituents of Medical Grand Rounds
      suggested a variety of important barriers. Understanding such barriers informs
      some recommendations to improve the program and possibly other programs similar
      to it. CONCLUSION: This study has identified important barriers to improving a
      specific grand rounds program and discusses the implications of such barriers on
      recommendations for improvement.

PMID- 19860274
TI  - Providing medical care to diverse populations: findings from a survey of
      Connecticut physicians.
AB  - OBJECTIVE: To identify current approaches and physicians' perceptions of
      challenges to providing medical care to racially, ethnically and culturally
      diverse patients in Connecticut. METHODS: Three hundred twenty-one licensed and
      practicing physicians in Connecticut representing 17 specialty areas completed a
      brief self-administered mail survey in the spring of 2009. RESULTS: Although
      physicians generally feel that they do a good job in treating patients from
      diverse racial, ethnic and cultural backgrounds, many do not employ best
      practices for communicating with patients with limited English proficiency. Many
      also do not tail or their discussions of health and health behavior to individual
      patients in a way that is culturally sensitive. Only 38% of all physicians had
      received formal training in managing patients from diverse backgrounds, and 34%
      had completed continuing medical education on this subject. Physicians reported
      that the greatest challenges to providing care to diverse patient groups involved
      structural issues such as medication costs and insurance issues. CONCLUSION:
      Findings from this study suggest that providing patients with better information
      on obtaining health insurance and how to utilize insurance coverage to access
      appropriate and effective medical care, as well as broad-based training and
      education in cultural awareness and sensitivity for both physicians and their
      office staffs, may be instrumental in decreasing health disparities among
      Connecticut residents.

PMID- 19860276
TI  - Sham peer review.

PMID- 19860277
TI  - Idealism and the reformation of health care in America.

PMID- 19860278
TI  - Physician as patient--case report.

PMID- 19860279
TI  - A portrait of the primary-care physician at age 65.

PMID- 19860280
TI  - 50 years ago from the Connecticut State Medical Journal. October 1959. Radiation
      therapy of acne.

PMID- 19860281
TI  - Anecdotal lessons on diversity.

PMID- 19860282
TI  - Health-care reform: do we count?

PMID- 19860283
TI  - Survey results focus CSMS commitment to education.

PMID- 19860284
TI  - The brain and its fabled cranial nerves.

PMID- 19860285
TI  - The evolution of the American Dentist. Part I--Amalgamation: 1776-1840.

PMID- 19860286
TI  - Dr. Arthur Davenport Black: his contributions to dentistry.

PMID- 19860287
TI  - The era of whiter teeth: advertising in American dentistry 1910-1950.
AB  - It has often been argued that the public image of dentists has been tainted by
      association with fear and pain into an image of evil 'psychodontists' and that
      there is an apparent lack of 'role models' in popular film, television, art and
      literature concerned with dentistry. This paper argues that we get a different
      picture when looking at different media. Advertisements introduce into a public
      domain, positive images of dentistry which crucially differ from the images found
      in other popular media. This paper traces the public image of dentistry in early
      20th-century America, as seen through dentifrice advertisements, and suggests
      three important reasons for studying advertisements: First, advertisements
      provide a supplement to studies of popular images of dentistry carried out so
      far. Second, advertisements have played an important part in advancing oral
      hygiene as a public concern. And third, advertisements provide the historian of
      dentistry with a unique opportunity for analyzing the complex and interwoven
      relationship of popular and professional discourses, since ads have acted as
      catalysts for professional discussions and self-reflection among dentists.

PMID- 19860288
TI  - The root of dental anatomy: a case for naming Eustachius the "father of dental
      anatomy".
AB  - When one considers the names of those whose affect on dentistry reached far
      beyond their lifetimes, one may think of Fauchard, Wells, Morton and Black. One
      name that deserves to be called among the pantheon of the greats is Bartholomaeus
      Eustachius. Eustachius was not the first to study the anatomy of the teeth and
      jaws, having been preceded by Da Vinci; however, he was the first to publish a
      treatise devoted entirely to this subject, Libellus de Dentibus, in 1563. As Sir
      William Osler, the father of modern medicine, stated: "In Science, the credit
      goes to the man who convinces the world, not to whom the idea first occurs." The
      purpose of this paper is to show that Eustachius deserves to be named the father
      of dental anatomy.

PMID- 19860289
TI  - Dental postcards XLII. Linen.

PMID- 19860290
TI  - Dental trade cards XXVII. Tweed's Liniment.

PMID- 19860291
TI  - Dentistry on stamps. Dr. Lowell's golf tee.

PMID- 19860292
TI  - Social workers as patient navigators for breast cancer survivors: what do African
      American medically underserved women think of this idea?
AB  - Patient navigation (PN) is a new initiative in health care aimed at reducing
      disparities by assisting patients in overcoming barriers within the health care
      system. As PN programs grow around the country, it is important to consult the
      key stakeholders in the development of these programs. The purpose of this
      qualitative study was to discuss the needs of medically underserved cancer
      patients and allow them the opportunity to provide input on models of care to
      meet their needs. Four focus groups were conducted in three major cities across
      Tennessee. Research participants (n = 36) were recruited by the staff in area
      cancer support programs and treatment programs across the state and through
      recruitment flyers at various treatment centers and community organizations.
      Findings revealed four key themes in the development of PN programs: (1) the PN
      needs to address access to quality care issues; (2) the PN needs to address the
      emotional and practical concerns of the cancer survivor, (3) the PN needs to
      address family concerns; (4) the PN needs to be involved across the continuum of
      care from time of diagnosis into long-term survivorship. Oncology social workers
      have a unique opportunity to meet the needs of medically underserved cancer
      patients through the PN movement. Our profession is a key stakeholder in this
      movement. We need to advocate for trained oncology social workers to actively
      pursue the role of patient navigators to ensure that the needs of medically
      underserved cancer survivors and their families are met.

PMID- 19860293
TI  - Integrating social workers into primary care: physician and nurse perceptions of
      roles, benefits, and challenges.
AB  - The primary aim of this article is to identify, from the perspective of primary
      care physicians and nurses, the challenges encountered in provision of health
      care to older adults and to identify potential roles, challenges, and benefits of
      integrating social workers into primary care teams. As more older adults live
      longer with multiple chronic conditions, primary care has been confronted with
      complex psychosocial problems that interact with medical problems pointing to a
      potential role for a social worker. From a policy perspective, the lack of strong
      evidence documenting the benefits that will accrue to patients and providers is a
      key barrier preventing the wider use of social workers in primary care. This
      article presents findings from three focus groups with primary care physicians
      and nurses to examine the perspectives of these key providers about the benefits
      and challenges of integrating social workers into the primary care team.

PMID- 19860294
TI  - Living in institutional care: residents' experiences and coping strategies.
AB  - Insights into daily living in residential care settings are rare. This article
      draws on a qualitative dataset (semi-structured interviews and recordings of
      residents' council meetings) that gives a glimpse of the experiences and coping
      strategies of (older) people living in residential care. The data highlight the
      range of unmet needs of the residents, similar to the categories of
      physiological, safety, love, esteem, and self-actualization needs in Maslow's
      hierarchy of needs theory. Our analysis indicates that "higher" and "lower" needs
      are closely intertwined and mutually reinforcing and should therefore be accorded
      equal emphasis by professionals (including social workers) employed within
      residential care settings.

PMID- 19860295
TI  - Treatment decision making and its discontents.
AB  - Patient participation in treatment decision making is held as a virtue in
      clinical contexts, and has much to recommend it. Yet important questions have
      been raised about the assumptions underlying models of patient participation.
      Debates have arisen about the significance of medically defined risks and
      outcomes of treatment; the adequacy and relevance across social groups of the
      concept of autonomy; and the emphasis on the professional-patient dyad. This
      article contributes to the debate about treatment decision making with reference
      to a study focused on older women with cancer. Interviews with patients and
      cancer care professionals highlighted the salience to patients' treatment choices
      of experiential knowledge, social roles and responsibilities, and the health
      policy context. It appears that prevailing models of decision making may obscure
      patients' more typical decision processes as well as the social determinants of
      those choices.

PMID- 19860296
TI  - At last! Hope for real health care reform.
AB  - This presidential inaugural address was delivered during the installation
      ceremony at NMA's 107th convention and scientific assembly in Las Vegas, Nevada,
      by NMA President Willarda V. Edwards, MD, MBA, July 28, 2009.

PMID- 19860297
TI  - Ethnic variations in quality of life and depressive symptoms among black
      Americans with acute decompensated heart failure.
AB  - BACKGROUND: Readmission rates for black Americans with heart failure are higher
      than for white Americans. Ethnic variations in quality of life (QOL) and
      depressive symptoms in black Americans with acute decompensated heart failure
      (ADHF) are understudied. OBJECTIVE: To assess the severity of depressive symptoms
      and their contribution to QOL in patients with ADHF receiving care at inner-city
      hospitals with high volumes of black patients. METHODS: Depressive symptoms and
      QOL measured using the Patient Health Questionnaire 9 (PHQ-9) and the Minnesota
      Living With Heart Failure Questionnaire (MLWHFQ), respectively, were assessed in
      134 nonhemodialysis patients with ADHF cared for in neighborhoods of New York
      City with more than 80% black residents. Univariate and multivariate methods were
      used to assess the effect of ethnicity on QOL and the contribution of depressive
      symptoms to QOL. RESULTS: Significant depression (PHQ-9 > or = 10) was found in
      45% of individuals; MLWHFQ scores for these patients were 61 +/- 20; 60% of
      patients were functionally impaired. Adjusted mean QOL scores were equivalent in
      the African American and Caribbean black groups. Depressive symptoms were equally
      severe in the 2 groups and explained an equivalent proportion (> 40%) of the
      variance in QOL in each group. CONCLUSIONS: Patients with ADHF cared for at
      centers with high volumes of black patients may have a high burden of depressive
      symptoms and a high prevalence of functional impairment because of depressive
      symptoms. Ethnicity among black Americans with ADHF does not predict QOL or
      severity of depressive symptoms.

PMID- 19860298
TI  - Indices of arterial stiffness in African American and African Caribbean subjects.
AB  - BACKGROUND: African American and African Caribbeans have high cardiovascular
      morbidity/mortality. Increased arterial stiffness is a marker of subclinical
      atherosclerosis, predicts higher cardiovascular risk, and causes isolated
      systolic hypertension. The objectives of the study were to compare arterial
      stiffness indices in African Americans and African Caribbeans and obtain
      reference values. METHODS/RESULTS: We prospectively studied 449 African Americans
      and 454 African Caribbeans. Using applanation tonometry, mean augmentation index
      and carotid-to-radial pulse-swave velocity were similar between the 2 groups (23
      +/- 15 vs 24 +/- 14%, p = .20) and (9.0 +/- 1.9 vs 9.0 +/- 2.0 m/s, p = .86). On
      multivariate analysis, age, weight, gender, mean arterial pressure, heart rate,
      and family history of coronary artery disease were independently associated with
      augmentation index in African Americans (R2, 0.46) and African Caribbeans (R2,
      0.49). Among 94 African American and 98 African Caribbean healthy subjects
      without cardiovascular risk factors/disease, augmentation index (20 +/- 14 vs 18
      +/- 16%, p = .43) and pulse-wave velocity (8.9 +/- 1.9 vs 9.0 +/- 1.5 m/s, p =
      .92) were similar. Age-based normative values were determined. CONCLUSION:
      Augmentation index and pulse-wave velocity and their related clinical factors are
      similar between African Americans and African Caribbeans. Age, weight, female
      gender, mean arterial pressure, heart rate, and family history of coronary artery
      disease are independent predictors of higher augmentation index in African
      Americans and African Caribbeans. Whether increased arterial stiffness improves
      risk stratification in these populations merits further study.

PMID- 19860299
TI  - Peripheral arterial disease: considerations in risks, diagnosis, and treatment.
AB  - Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis,
      is a marker for coronary artery, cerebrovascular, and renal artery
      atherosclerotic vascular disease. Patients with PAD have an increased risk of
      cardiovascular events such as myocardial infarction and stroke in addition to
      significant impairment in their quality of life and physical function. Early
      detection and implementation of guideline-recommended therapies are paramount to
      effective treatment of PAD. Measurement of the ankle-brachial index is a simple,
      reliable, and noninvasive test to diagnose PAD that can be used in a primary care
      setting. Lifestyle modification, including exercise and smoking cessation,
      combined with pharmacologic therapy to manage risk factors have been shown
      effective in reducing cardiovascular risks in patients with PAD. Evidence
      suggests, however, that there is currently a lack of awareness regarding PAD
      among physicians and patients, leading to underdiagnosis and undertreatment. This
      paper reviews the epidemiology, pathology, and clinical implications of PAD, and
      offers current evidence for disease management quality improvement initiatives to
      enhance patient care.

PMID- 19860300
TI  - Weight gain, related concerns, and treatment outcomes among adolescent smokers
      enrolled in cessation treatment.
AB  - We examined associations of weight concerns and weight gain with adolescent
      tobacco cessation treatment and whether these effects differed by gender or
      ethnoracial group. Participants were 115 urban adolescents recruited for a
      randomized clinical trial of nicotine replacement therapy. Baseline weight gain
      concerns were assessed using the Eating Disorders module from the Diagnostic
      Interview for the Child and Adolescent (DICA-IV). The average weight gain during
      the trial was 0.59 +/- 2.85 kg among the 43.5% of participants who completed the
      treatment study. As indicated by the DICA, baseline weight gain concerns were not
      associated with weight gain during treatment, study completion, or abstinence
      from smoking at 3-month posttreatment follow-up; these results did not vary by
      gender or ethnoracial group. Adolescents who quit smoking gained no more weight
      during the trial than those who smoked.

PMID- 19860301
TI  - Diabetic retinopathy, dilated eye examination, and eye care education among
      African Americans, 1997 and 2004.
AB  - OBJECTIVE: To examine diabetic retinopathy, dilated eye examination, and eye care
      education among African Americans before and after a community-level public
      health intervention. METHODS: We analyzed data from Project DIRECT (Diabetes
      Interventions Reaching and Educating Communities Together) participants with self
      reported diabetes (617 in 1996-1997 and 672 in 2003-2004) in Raleigh
      (intervention community) and Greensboro (comparison community), North Carolina.
      All analyses were weighted to adjust for the complex sample design of pre and
      post cross-sectional surveys. Estimates were age standardized to the 2000 US
      Census population. We used multivariate logistic regression to calculate odds
      ratios and corresponding 95% confidence intervals. RESULTS: We found no
      significant difference in prevalence of diabetic retinopathy between the control
      and intervention communities (p > .05). However, after adjusting for other
      confounders, receipt of eye care education (OR, 1.59; 95% CI, 1.19-2.13) was
      independently associated with receipt of dilated eye examination among African
      Americans with diabetes. Compared with individuals without diabetic retinopathy,
      those with diabetic retinopathy were more likely to use eye care services (OR,
      1.89; 95% CI, 1.41-2.54). CONCLUSIONS: Diabetic retinopathy is a considerable
      problem among African American communities. Community intervention efforts, such
      as comprehensive eye care education, that specifically target improvement in
      diabetic retinopathy and use of eye are services could help better serve this
      population.

PMID- 19860302
TI  - A systematic review of barriers and interventions to improve appropriate use of
      therapies for sickle cell disease.
AB  - Clinical experts have expressed concern about underutilization of sickle cell
      disease (SCD) therapies, including hydroxyurea, prophylactic antibiotics, iron
      chelation, bone marrow transplantation, pain management during vaso-occlusive
      crisis, and receipt of routine ambulatory health care. We synthesized studies
      that identified barriers to and interventions to improve appropriate use of these
      therapies. Of the 48 studies included in our review, 35 identified therapeutic
      barriers or facilitators, and 13 evaluated interventions to improve use of
      therapies. Consistently identified barriers to appropriate pain management were
      negative provider attitudes and lack of provider knowledge. Four of 9 pain
      management interventions improved direct measures of pain management quality,
      while 5 improved indirect measures. One intervention improved receipt of routine
      ambulatory care. We concluded that interventions to improve pain management in
      SCD can be effective and should address providers' negative attitudes and
      knowledge and that more intervention studies are needed to improve receipt of
      recommended SCD therapies.

PMID- 19860303
TI  - End-of-treatment smoking cessation among African American female participants in
      the Breathe Free for Women smoking cessation program: results of a pilot study.
AB  - OBJECTIVE: Quitting smoking is particularly imperative for African American women
      due to their disproportionate rates of smoking-related morbidity and mortality.
      However, very few smoking cessation interventions have demonstrated successful
      quit rates for African American women. This study sought to examine the Breathe
      Free for Women (BFFW) smoking cessation lifestyle program among African American
      female smokers. The primary objective of the pilot project was to examine end-of
      treatment quit rates, and the secondary objective sought to obtain feedback from
      African American female participants on the acceptability of the intervention in
      this population. METHODS: A total of 42 African American females were recruited
      to participate in 1 of 6 intervention cohorts. Each intervention cohort
      participated in 9 group sessions presented over a period of 4 weeks. Participants
      complete an investigator developed survey assessing current smoking status as
      well as impressions of each intervention session. RESULTS: An end-of-treatment
      quit rate of 19% was achieved with an average study retention rate of 70%. In
      addition, participants' feedback indicated that the BFFW intervention offers a
      highly promising model for enhanced tailoring by incorporating socioculturally
      relevant methods, materials, and content. CONCLUSIONS: Future research must
      address the critical public health need for socioculturally relevant adaptations
      of existing and promising smoking cessation programs for African American women.

PMID- 19860304
TI  - Using the Pregnancy Perception of Risk Questionnaire to assess health care
      literacy gaps in maternal perception of prenatal risk.
AB  - In order to make appropriate decisions, patients must be able to understand and
      use the context-specific health information with which they have been provided,
      and health providers must be able to convey information to patients who possess
      varying degrees of health literacy. Adherence to medical recommendations often
      depends on patient perception of their medical risks and the importance they
      attach to those risks. In obstetrics, maternity patients are generally identified
      as high risk or non-high risk (routine). Conferring the designation of "high
      risk" may confer additional benefits in educational efforts, literacy evaluation,
      and relief of educational barriers to care that are reflected in high-risk
      patients' higher assessments of their risks. In this study, medically identified
      risk factors were reviewed for patients in the high-risk and routine obstetrical
      clinics. Patients labeled as "routine" might still possess significant numbers
      and types of medically identified risk factors (MIFs) due to patients'
      socioeconomic status and health risks. If prenatal risk is a spectrum, adaptation
      of obstetrical health care materials and culturally appropriate counseling may
      mitigate gaps between patient understanding of their MIF number and type and
      patient risk perception in order to reach the goal of universally improved
      patient adherence to medical recommendations.

PMID- 19860305
TI  - Exposure to hydroxyurea and pregnancy outcomes in patients with sickle cell
      anemia.
AB  - The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) was a randomized
      double-blind placebo-controlled trial to test whether hydroxyurea could reduce
      the rate of painful crises in adults who had at least 3 painful crises per year.
      Because hydroxyurea is known to be carcinogenic, mutagenic, and teratogenic in
      animals, a major inclusion criterion in MSH was the use of contraceptives both by
      females and males in order to avoid exposure of the fetus to hydroxyurea. Despite
      this precautionary measure, some women became pregnant while taking hydroxyurea
      or their male partners were on hydroxyurea. We followed surviving patients who
      were enrolled in the original MSH trial for up to 17 years postrandomization. Our
      findings suggest that exposure of the fetus to hydroxyurea does not cause
      teratogenic changes in those pregnancies that terminate in live birth whether
      full-term or premature. This seems to be true whether the parent taking
      hydroxyurea was the mother or the father. The same argument seems to apply for
      exposure to opioids. However, it will take a much longer follow-up of many more
      hydroxyurea-exposed sickle cell disease subjects to establish the results
      conclusively.

PMID- 19860306
TI  - Using quantitative and qualitative approaches to understand racial disparities in
      adult vaccination.
AB  - BACKGROUND: One proposed explanation for the persistence of racial disparities in
      adult immunizations is that minority patients receive primary care at practices
      that differ substantively from practices where white patients receive care. This
      study used both quantitative and qualitative methods to assess physician and
      practice factors contributing to disparities in a sample of inner-city, urban,
      and suburban practices in low to moderate income neighborhoods. METHODS:
      Pneumococcal polysaccharide vaccine (PPV) and influenza vaccination rates were
      determined from medical record review in a sample of 2021 elderly (aged > or = 65
      years) patients. Their physicians were surveyed about office systems for adult
      immunizations and structured observations of practice physical features, and
      operations were conducted. Case studies of practices with lowest and highest
      rates and the largest racial disparities are presented. RESULTS: Overall,
      weighted PPV vaccination rate was 60%, but rates differed significantly by race
      (65.8% for whites vs 36.5% for minorities, P < .001 by stratified Cochran-Mantel
      Haenszel test). Two of 6 minority panels had PPV rates less than 20%. Overall,
      weighted influenza vaccination rate, as measured by receipt of the vaccine in 3
      of the 5 most recent seasons, was 51.9%, but rates also differed significantly by
      race (55.6% for whites vs 36.2% for minorities, P < .03, by stratified Cochran
      Mantel-Haenszel test). CONCLUSIONS: Low rates in 2 minority panels, racial
      disparity between minorities and whites in mixed panels, and between-panel
      variation in rates contributed to the overall differences in vaccination rates by
      race.

PMID- 19860307
TI  - Small cell carcinoma of the breast.
AB  - We report the case of an 81-year-old woman with limited-stage small cell
      carcinoma of the left breast who presented with multiple painful nodules in the
      left breast. The patient was treated with systemic chemotherapy and consolidation
      radiation therapy without undergoing surgery. To our knowledge, this is the first
      report in the literature of small cell carcinoma of the breast managed
      definitively with chemotherapy and local-regional irradiation for which the
      details of treatment are explicitly described.

PMID- 19860308
TI  - Sickle cell disease in a "postracial" America.
AB  - Sickle cell disease was first identified as a clinical syndrome in the United
      States nearly 100 years ago. Since that time, perhaps no other medical condition
      has been as strongly associated with the concept of "race." In this commentary,
      the authors integrate multidisciplinary perspectives to argue for more rigorous
      analyses of how perceiving sickle cell disease through racial lenses impacts its
      public image and, more importantly, its perception among health care providers.
      The authors assert that concerted efforts involving collaborations among media,
      community-based organizations, medical professionals, and health care policy
      makers are needed to challenge popular misconceptions about sickle cell disease
      heritability and risk.

PMID- 19860309
TI  - Why we should still publish in JNMA more than 25 years later.

PMID- 19860310
TI  - Adoption status and psychological distress in black patients with sickle cell
      disease.

PMID- 19860312
TI  - Nurses have a responsibility to voice opinions on healthcare reform.

PMID- 19860311
TI  - Baker et al overlook Memphis' Dr Myles V. Lynk, NMA pioneer.

PMID- 19860313
TI  - Health policy advocacy. Oncology nurses make a difference.

PMID- 19860314
TI  - What is the most pressing health policy issue facing oncology care and
      prevention? Nurse works to ensure access to care and coverage for services.

PMID- 19860315
TI  - Study looks at oncology nurses' perceptions of outpatient cancer care in light of
      MMA changes.

PMID- 19860316
TI  - Identify and treat sleep-wake disturbances in patients with cancer.

PMID- 19860317
TI  - Why did ONS retire the Steering Council?

PMID- 19860318
TI  - Radiation may be unnecessary for children with leukemia.

PMID- 19860319
TI  - [Characteristics and clinical efficacy of the sustained-release formulation of
      azalide azithromycin].

PMID- 19860321
TI  - [Changes over 10 years of ampicillin-resistant Haemophilus influenzae isolated
      from children].
AB  - We examined the frequency of ampicillin (ABPC) resistance of 3784 strains of
      Haemophilus influenzae isolated from the infants aged from 1 month after birth to
      12 years who had been treated in the Pediatric Department of our hospital for 9
      years and 6 months from July 1999 to December 2008. We determined the drug
      susceptibility by Etest, and judged the resistance by the standard of Clinical
      and Laboratory Standard Institute. The rate of strains of MIC of less than 2
      microg/ml to ABPC was 87.1% in 1999, but the ratio was decreasing year after year
      significantly up to 28.7% in 2008 (p < 0.001). beta-lactamase negative ABPC
      resistant (BLNAR) strains whose MIC to ABPC was more than 4 microg/ml was 2.9% in
      1999, but increased significantly to 43.3% in 2008 (p < 0.001). MIC90 was 2
      microg/ml in 1999, but increased to 16 microg/ml in 2008.

PMID- 19860320
TI  - [Bacteria isolated from surgical infections and their susceptibility to
      antimicrobial agents--special reference to bacteria isolated between April 2007
      and March 2008].
AB  - Bacteria isolated from infections in abdominal surgery during the period from
      April 2007 to March 2008 were investigated in a multicenter study in Japan, and
      the following results were obtained. In this series, 707 strains including 24
      strains of Candida spp. were isolated from 181 (79.0%) of 229 patients with
      surgical infections. Three hundred and ninety-five strains were isolated from
      primary infections, and 288 strains were isolated from postoperative infections.
      From primary infections, anaerobic Gram-negative bacteria were predominant,
      followed by aerobic Gram-negative bacteria, while from postoperative infections
      aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram
      negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of
      Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus
      spp. in this order, from primary infections, while Enterococcus spp. was highest,
      followed by Staphylococcus spp. from postoperative infections. Among aerobic Gram
      negative bacteria, Escherichia coli was the most predominantly isolated from
      primary infections, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa and
      Enterobacter cloacae, in this order, and from postoperative infections, P.
      aeruginosa was most predominantly isolated, followed by E. cloacae, E. coli and
      K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rate of
      Parvimonas micra was the highest from primary infections, followed by
      Streptococcus constellatus and Gemella morbillorum, and from postoperative
      infections, Anaerococcus prevotii was most predominantly isolated. Among
      anaerobic Gram-negative bacteria, the isolation rate of both Bacteroides fragilis
      and Bilophila wadsworthia were the highest from primary infections, followed by
      Bacteroides thetaiotaomicron and Campylobacter gracilis, and from postoperative
      infections, B. thetaiotaomicron was most predominately isolated, followed by B.
      fragilis, Bacteroides caccae and B. wadsworthia in this order. In this series, we
      noticed no vancomycin-resistant Gram-positive cocci, nor multidrug-resistant P
      aeruginosa. There were nine strains of coagulase-negative Staphylococci which
      show higher MIC against teicoplanin more than 4 gg/mL, but all of them had good
      susceptibilities against various anti-MRSA antibiotics. We should carefully
      follow up B. wadsworthia which was resistant to various antibiotics, and also
      Bacteroides spp. which was resistant to many beta-lactam antibiotics.

PMID- 19860323
TI  - [A novel population of calretinin-positive, presumably non-neuronal, cells with
      the polymorphous spines in mouse forebrain].
AB  - Using the immunocytochemical method, the localization of calretinin-positive
      cells was studied in the frontal sections of anterior portion of the mouse
      cerebral hemispheres. The population of cells with a characteristic structure,
      that was not described previously, was detected in the area of anterior horns of
      lateral brain ventricles. These cells have small (8-10 microm) rounded perikarya
      which gave rise to 1 or, rarely, 2 nodose processes covered with widely spaced,
      polymorphous spines (PS) and irregular thickenings. Primary, relatively thick,
      processes divide to produce thinner processes that also formed thickenings and
      spines of different dimensions and structure. Calretinin-positive cells with PS
      (CR+PS) cells are located in the white subcortical matter, layer VI, more rarely
      in layer V of the frontal area of dorsomedial cortex close to the cingulum. CR+PS
      cells were also present in rostro-dorsal part of the caudate nucleus-putamen
      complex, anterior olfactory nucleus, subependymal layer of the dorsolateral angle
      of the lateral ventricle, and, less frequently, near its dorsal wall. In contrast
      to mouse brain, CR+PS cells were not found in the brain of other animals (rats,
      rabbits, cats).Within CR+PS cells, no co-localization of calretinin with GABA and
      other neuronal or glial markers was found. It is suggested that the cells
      described represent previously unknown, presumably non-neuronal type of the mouse
      forebrain.

PMID- 19860324
TI  - [Effect of ethanol on the density of neuron disposition in limbic cerebral cortex
      and correction of induced changes with antioxidant Dolivin].
AB  - The purpose of this study was to determine the density of neuron disposition at
      the early stages of postnatal development of limbic cortex in the offspring of
      female rats, that consumed 15% ethanol solution during pregnancy and lactation
      period instead of water, and to detect the possibility of the correction of
      ethanol-induced changes with antioxidant Dolivin. The number of neurons in the
      cingulate girus and entorhynal cortex was determined at different stages of
      postnatal development (postnatal days 3, 7, 15, 21, 30). With an aim to correct
      ethanol-induced disorders, alcoholized females for the similar period of time,
      were given Dolivin (0.7 mg daily). It was shown that the cytotoxic effect of
      ethanol resulted in the decrease in the neuron numbers at the early stages of
      postnatal development, particularly at day 7. The neurons most sensitive to the
      ethanol action were observed in the deeper limbic cerebral cortex. The
      application of Dolivin has demonstrated its preventive effect, by weakening the
      ethanol cytotoxicity at the all stages of postnatal development.

PMID- 19860325
TI  - [The connections of the zona incerta of the dog diencephalon with the substantia
      nigra, the ventral tegmental area and the pedunculopontine tegmental nucleus].
AB  - This study used the technique based on horse-radish peroxidase retrograde and
      anterograde transport to examine the organization of the connections of different
      sectors of the zona incerta (ZI) of the diencephalon with the substructures of
      the substantia nigra, the ventral tegmental area and the pedunculopontine
      tegmental nucleus of dog mesencephalon. It was found that these structures were
      interconnected with each other. In the organization of the projections studied,
      the elements were detected that suggested the possibility of the segregated
      conduction of the functionally various information via the established pathways.
      Alongside with this, the convergence of the projection fibres of the neurons of
      the mesencephalic nuclei substructures to ZI, described in all its sectors,
      together with the projections of all the ZI sectors to these neurons, indicates
      the possibility of the integration of functionally various information both at ZI
      level and at the level of mesencephalic structures studied in this work.

PMID- 19860322
TI  - [In vitro susceptibilities to levofloxacin and various antibacterial agents of
      12,919 clinical isolates obtained from 72 centers in 2007].
AB  - We have reported in this journal in vitro susceptibilities of clinical isolates
      to antibiotics every year since 1992. In this paper, we report the results of an
      analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers
      in Japan to selected antibiotics in 2007 compared with the results from previous
      years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus
      pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high
      susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to
      macrolides has been increasing every year and this was especially clear this
      year. Most strains of Enterobacteriaceae except for Escherichia coli showed a
      high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs
      and the resistance increased further this year. FQs resistance of methicillin
      resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception
      of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S.
      aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant
      coagulase negative Staphylococci (MRCNS) was higher than that of methicillin
      susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that
      of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs
      resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of
      Enterococcusfaecium was more than 85% except for STFX (58.3%). In clinical
      isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs
      resistance was 21-27%, which was higher than that of P. aeruginosa from
      respiratory tract infections at 13-21%, which was the same trend as in past
      years. Multidrug resistant strains accounted for 5.6% in the urinary tract and
      1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to
      FQs. The carbapenem resistant strains, which present a problem at present,
      accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86-88% to
      FQs. The results of the present survey indicated that although methicillin
      resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae
      showed resistance tendencies, and other species maintained high susceptibility
      rates more than 90% against FQs, which have been used clinically for over 15
      years.

PMID- 19860326
TI  - [Satellite cells of the sensory neurons after different types of sciatic nerve
      trauma in rat].
AB  - The reaction of satellite cells (SC) and the changes in their numbers were
      studied in rat lumbar dorsal root ganglia using the models of sciatic nerve
      crush, transection and ligation. After the nerve transection, the neurons
      surrounded by two layers of SC were found. This was accompanied by the increased
      SC branch thickness and contact area due to invaginations into neuronal
      perikarya. After the nerve ligation, both SC and their branches were found to
      form several closely adjacent layers around the part of the large and medium
      neurons, the area of SC contact with the perikarya of neurons of these
      populations was increased due to more developed invaginations, there appeared the
      multilamellar structures in SC cytoplasm and the contacts with the branches of
      SC, which surrounded the neighboring neurons. The most pronounced increase in SC
      numbers was demonstrated after the nerve ligation. After the nerve transection,
      the numbers of small and medium neurons, surrounded by vimentin-positive SC, was
      increased. At the same time, the number of large neurons surrounded by these
      cells, was decreased. At all time intervals after the nerve ligation, all the
      neurons in the ganglia studied were surrounded by vimentin-positive SC. Post
      traumatic changes in structure and numbers were different in SC, associated with
      specific populations of sensory neurons and depended on type of afferent
      conductor injury.

PMID- 19860327
TI  - [Efferent innervation of the arteries of human leptomeninx in arterial
      hypertension].
AB  - Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and
      cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of
      human leptomeninx with different diameters. Material was obtained from the
      corpses of the healthy people and of the patients with initial stages of arterial
      hypertension (AH). It was shown that the concentrations of cholinergic and
      adrenergic nerve fibers and varicosities in axon terminal part, innervating the
      arteries with the diameters ranging from 450 till 100 microm, were not
      significantly different. In these arteries, NO-ergic plexuses were also detected.
      In patients with AH, regardless the arterial diameters, the significant increase
      (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found.
      The changes in cholinergic nerve fiber concentration were found to depend on the
      vessel diameter: the significant decrease of these parameter was observed only in
      arteries with the diameter of 100-200 microm. No significant changes in nerve
      plexus concentration was noticed in the arteries with greater or smaller
      diameter. In NO-ergic neural conductors, the enzyme activity decreased only in
      the large arteries, and remained almost unchanged in the small vascular branches.
      The changes in the vasomotor innervation described in AH, are interpreted as a
      vasomotor innervation dysfunction of the leptomeninx arteries that may result in
      the hemodynamic disturbances.

PMID- 19860328
TI  - [Morpho-functional interactions of the iris peripheral nervous fibers with the
      neurons developing in the rat anterior eye chamber].
AB  - The intraocular grafts of the septal or hippocampal embryonic tissues developing
      in the rat anterior eye chamber for three to four months were investigated by
      electron microscopy. The aim of this study was both the ultrastructural
      identification of the peripheral nervous fibers entering the grafts from host
      iris and the estimation of their capacity to establish true synaptic contacts
      with the central nervous system neurons of the grafts. The bundles of myelinated
      and unmyelinated axons, surrounded by the Schwann cell cytoplasm, were observed
      within the perivascular spaces of the ingrowing blood vessels. In the neuropil
      areas of the grafts, both types of the peripheral nervous fibers were also
      identified. It was demonstrated on the ultrastructural level that the
      unmyelinated axons lost their glial envelope of the Schwann cell and formed the
      typical asymmetric synapses with the dendrites and dendritic spines of the
      grafted neurons. The results are indicative of the high morpho-functional
      plasticity of both parts of the nervous system.

PMID- 19860329
TI  - [Differences in the functional activity of human neutrophilic granulocytes in
      their interactions with semiconductor quantum dots].
AB  - The uptake of quantum dots (QD-5 nm particles of CdSe/ZnS-mercaptoacetic acid) by
      human neutrophilic granulocytes was studied using the methods of scanning laser
      and scanning probe microscopy. The results show that the neutrophilic
      granulocytes may be subdivided into three subpopulations: (1) the cells with no
      uptake of QD (10.0 +/- 2.0%); (2) cells that accumulate QD in their volume (28.0
      +/- 1.9%), and (3) cells, surrounded by a halo of QD (59.0 +/- 2.2%). The
      dispersion of these characteristics may suggest the differences in neutrophilic
      granulocyte plasma membrane permeability.

PMID- 19860330
TI  - [The structure of the rat lymph nodes draining purulent inflammation region after
      interleukin-2 treatment].
AB  - The structure of rat lymph nodes regional to the purulent wound under the
      conditions of interleukin (IL-2) treatment was investigated by the methods of
      light microscopy. In the lymph nodes from intact animals, the cortical plateau
      was found to become diminished with the simultaneous paracortical zone expansion.
      In the regional lymph nodes from rats with an untreated purulent wound, the
      relative dimensions of cortical plateau were decreased because of expansion of
      the medullary structures. Lymphoid parenchyma and the sinuses of lymph nodes
      contained erythrocytes, the numbers of immuno- and plasmoblasts, macrophages and
      neutrophilic granulocytes were increased. IL-2 treatment in animals with a
      purulent inflammatory reaction secured the greater integrity of structure of
      these organs and of cytoarchitecture of their various zones. However, the
      administration of this cytokine resulted in increased vascular permeability and
      enhanced the probability of allergic reaction development, which requires the
      development and application of prophylactic measures of the specified side
      effects and complications.

PMID- 19860331
TI  - [Morphometric study of the grouped lymphoid nodules in Wistar rats with different
      behavioral activity exposed to acute stress].
AB  - This paper describes the results of the study of the structural elements of the
      grouped lymphoid nodules (GLN, Peyer's patches) of rat ileum after the exposure
      to emotional-painful stress. In the control group of behaviorally passive rats,
      the area, occupied by GLN structural elements in the intestinal sections, was
      significantly greater than that one in the group of active rats. After the
      exposure to stress, the areas of all GLN structural components were decreased in
      the behaviorally passive rats. In the group of behaviorally active rats exposed
      to stress, the areas occupied by the GLN internodular zones, were increased,
      while the areas of lymphoid nodules remained practically unchanged, suggesting
      high adaptation capacity of this group of animals.

PMID- 19860332
TI  - [Neuroendocrine complexes in the pancreas of nutria (Myocastor coypus) (an
      immunohistochemical study)].
AB  - With the application of a double immunohistochemical labeling method, several
      types of neuroendocrine interactions were demonstrated in the pancreas of nutria.
      Two types of neuroinsular complexes were detected that have the organization
      typical to the mammals. It was found to be typical of nutria that several
      pancreatic islets were integrated with nerve cells and nerve fibers. The
      complexes detected that reflect the interactions between nervous elements and
      single endocrine cells or their small groups, are species-specific. The data
      obtained demonstrate the diversity of neuroendocrine interactions in the pancreas
      and possible influence of the nervous system on B-cell differentiation.

PMID- 19860333
TI  - [Liver, kidney and a lung structure in rats after intravenous magnetoliposome
      administration].
AB  - This work examines the effect of magnetoliposomes on the basis of Fe3O4
      nanoparticles following different time intervals after their single intravenous
      injection, on the liver, kidney and lung structure in rats. Sections were stained
      with hematoxylin and eosin, and Perls method was used to demonstrate Fe+3 ions.
      It was shown that shortly after intravenous injection of magnetoliposomes,
      hemodynamic disturbances developed in all the organs studied, which by day 14
      were aggrevated by focal necroses and dystrophic changes in the liver and
      kidneys. Accumulation of nanoparticles in the cells of mononuclear phagocyte
      system of these organs was demonstrated. Damaging effect of magnetoliposomes on
      liver, kidney and a lung structure was established, which was caused by
      ultradisperse Fe3O4 particles contained in them. The consequences of this
      influence for the rat organism at the time periods exceeding the duration of our
      experiment, may hardly be predicted.

PMID- 19860334
TI  - [Langerhans cells of the interfollicular epidermis and external root sheath
      epithelium of the hair follicles of the normal human skin and in death caused by
      freezing].
AB  - The skin obtained from 50 cadavers of the individuals of both sexes who died as a
      result of general cooling was studied during a post-mortem examination in Vitebsk
      District Administration of The State Medical Forensic Expertise Service
      (Byelorussia). As the control, the skin of 10 people who died in car accidents
      and for other reasons, not associated with the effect of cold, as well as the
      skin samples taken from 10 healthy volunteers, were studied. Langerhans cells
      (LC) of the epidermis and hair follicle epithelium were studied using the ATPase
      reaction. LC structure under normal condition is described in detail. It was
      shown that these cells were localized in the suprabasal layer of the epidermis
      and of the epithelium of the external root sheath of the hair follicles. LC were
      forming contacts with one another by their long processes. In individuals who
      died as a result of general cooling, the number of LC was decreased both in the
      epidermis and in the epithelium of the external root sheath of the hair follicles
      and these cell underwent marked degenerative changes.

PMID- 19860335
TI  - [Comparative analysis of the anthropometric parameters and body component content
      in girls with the disturbances of sexual development of chromosomal and non
      chromosomal genesis].
AB  - 195 girls aged 14-16 years with the disturbances of sexual development of
      chromosomal and non-chromosomal genesis were examined. In girls with Shereshevsky
      Turner syndrome, the body mass and length, as well as the relative adipose tissue
      content, were significantly decreased as compared with those in girls with the
      disturbances of sexual development of non-chromosomal genesis. The differences in
      somatotype distribution between these groups were detected. The majority of the
      girls with Shereshevsky-Turner syndrome with karyotype changes (monosomy of X
      chromosome) had stenoplastic somatotype (70.6%). Among the girls with amenorhhea
      of non-chromosomal genesis, the stenoplastic (33.3%) and subathletic somatotypes
      (33.3%) prevailed. In both groups of girls with the disturbances in sexual
      maturation, the absence of athletic somatotype was noted.

PMID- 19860336
TI  - [The study of cerebral astrocyte spatial organization using confocal laser
      microscopy].
AB  - Three-dimensional reconstruction of cytoarchitectonic relations of the main
      components of the nervous tissue appears to be an important, yet an extremely
      laborious task of neuromorphology. The aims of the present study were: to develop
      the method permitting accurate visualization of astrocytes in rat brain slices
      thicker then 30 microm, to create an adequate algorithm for the study of the
      slides received using a confocal microscope and to perform the three-dimensional
      reconstructions of astrocytes from Z-series of confocal images. Different
      variants of slide preparation (various clearing reagents, fluorochromes, mounting
      media) were investigated, together with the operating modes of confocal
      microscope, methods of digital image processing etc. The methodical approaches
      are recommended that may be successfully applied for three-dimensional
      reconstruction and detection of spatial relations of astrocytes in mammalian
      brain.

PMID- 19860337
TI  - [To 275th anniversary of birth of Kaspar Friedrich Wolff (1734-1794) and to 250th
      anniversary of publication of his work "Theoria generationis"].

PMID- 19860338
TI  - [To 55th anniversary of the discovery of the double helix structure of DNA and to
      the 80th anniversary of birth of James D. Watson. James D. Watson's visit to
      Russia (2008)].

PMID- 19860339
TI  - Obama remarks at the National Academy of Sciences.

PMID- 19860340
TI  - [The discrete horror of cloning].
AB  - The author raises the topic of cloning after the decision of the Argentine
      government, which concerned for the "dignity of the human person", passed a
      decree of need and urgency, No. 200/97 (Annex), prohibiting cloning experiments
      with human beings. Therefore, considering that the topic is so terribly urgent
      and necessary, the author feels it is timely to consider it.

PMID- 19860341
TI  - Prenatal diagnosis and the trouble with eugenics.
AB  - In the past few years we have witnessed huge steps forwards in reproductive
      technology. Specifically genetic diagnosis has created a range of possibilities.
      This carries along benefits for prenatal care as well as carrying along
      unprecedented ethical dilemmas that demonstrate some more problematic sides of
      several basic notions in medical ethics. These new technologies also led to a
      widespread public ethical debate on the desirability of these technologies.
      Concerns are felt specifically with the potential eugenic application of these
      technologies. To have a correct overview of the possibilities to a new eugenics,
      one needs to explore the actual developments in the field of human genetics in
      recent years. This is important to avoid deviating from what is actually
      occurring into the realm of science fiction.

PMID- 19860342
TI  - [Cloning: necessary reflections on the imaginary].
AB  - The article covers the innumerable reasons given for using cloning for
      therapeutic and reproductive purposes. The most commonly used argument in favour
      of the procedure has been that of preserving human dignity, which would include
      the wide exercising of personal autonomy without restrictions of an ethical
      nature. This view is countered by questions relating to the use of the technique,
      namely self-determination and the loss of the integrity of the species, which
      would include the transformation of a generation through the production of human
      beings and tissues. It must also be made clear that therapeutic cloning (which is
      carried out through the use of stem cells) is not yet a reality in the scientific
      world, with the result that the procedure that is supposedly necessary, which
      argues in favour of the destruction of the young embryo is misleading, as are
      also certain discourses used to refer to the theme and the science. Criminal law,
      on prohibiting this practice is anticipating it becoming a reality, protecting
      legal rights that affect supra-individual interests, such as the destruction of
      the young embryo, one of the issues of concern to ADIN (Accion Directa de
      Inconstitucionalidad en Brasil - Direct Action on Unconstitutionality in Brazil)
      3510-0.

PMID- 19860343
TI  - [Antiscientific attitudes in open society].
AB  - The social controversy created in regard to the use and experiments with
      transgenic seeds and organisms serves as an example to illustrate the effects and
      consequences that can lead to antiscientific attitudes, which have gained great
      force in contemporary society. It has been suggested that the same functional
      relationship, from which the Enlightenment, science, and liberalism were born, is
      currently being applied in the opposite direction, so that the current
      antiscientific attitudes, along with the support they receive from post-modern
      thought, can end up undermining the bases of an open and democratic society. The
      consequences of this phenomenon are already manifested by the approval of certain
      regulations that lack scientific basis.

PMID- 19860344
TI  - [Scope of the cause of justification of the legitimate exercise of a right in the
      area of genetic criminality].
AB  - The Spanish penal Code of 1995 creates various crimes in relation to
      biotechnology, namely, the offence of genetic manipulation, the offence of
      cloning and the offence of fertilization of human eggs for purpose others than
      procreation. These new offences seek to protect new legal interests. But besides
      these interests, we must not forget that there also exist certain rights of the
      person that rely on reproductive and genetic technologies to be fully effective.
      That is why it is inevitable to bring to the discussion other interests of a
      different nature that may be in conflict with these new legal interests. This is
      the case in relation to the right to procreate and the right to scientific
      research. According to Article 20.7 of the Spanish penal Code, a person may
      justifiably engage in conduct that satisfies the elements of an offence if he has
      a right to do so. In this work the author analyses if certain conduct that could
      harm some legal interests, and therefore would be criminally punishable could be
      justified on the basis of the abovementioned rights to procreate and to undertake
      scientific research.

PMID- 19860345
TI  - [Comment on the bill modifying the Law on prevention of congenital defects in
      Argentina].
AB  - The author analyzes the bill modifying the Prevention of Congenital Handicaps
      Acts, as it is an issue affecting thousands of fertile women and their children's
      health. The text includes various topics as diet, foetal anomalies and
      termination of pregnancy, with its ethical and legal consequences.

PMID- 19860346
TI  - [Legal regime of preservation of data on identifiers obtained form DNA analysis,
      in the light of the Decision of the European Tribunal of Human Rights (Large
      Chamber), of December 4 2008 (S. and Marper vs. United Kingdom)].
AB  - The author analyzes the Judgement of the European Court of Human Rights, of 4
      December 2008 (case of S. and Marper v. the United Kingdom). It declares that
      retaining fingerprints and cellular samples and DNA profiles after the criminal
      proceedings, when the accused has been acquitted, constitutes a violation of
      Article 8 of the Convention for the Protection of Human Rights and Fundamental
      Freedoms. He also deals with the legal regime on data protection contained in the
      Spanish Law on police DNA databases of (Organic Law 10/2007, of 8 October), as
      well as its adaptation to the case law of the ECHR.

PMID- 19860347
TI  - [Family law, witness of the analysis of prenatal paternity].
AB  - The authors analyse from a scientific and legal perspective, how paternity
      analysis in the prenatal period can be reliably performed exactly the same as
      with newborns, and therefore, establish kinship in accordance with established
      regulations. In other words, there is an option for those who might not want to
      wait until birth to establish kinship.

PMID- 19860348
TI  - Key principles relating to genetic testing and insurance.
AB  - This report is a result of CDBI Working Party on Productivity, Genetic Testing
      and insurance, that took place in 2009.

PMID- 19860349
TI  - [Documents on the protection of personal data of children. Article 29 - Working
      Group on data protection].

PMID- 19860350
TI  - Failure to have menses following progesterone withdrawal in a normal estrogenic
      woman with polycystic ovarian syndrome who menstruates with oral contraceptives.
AB  - PURPOSE: To evaluate a case of a normal estrogenic woman with amenorrhea and
      polycystic ovarian syndrome who fails to get menses after progesterone withdrawal
      but who menstruates with oral contraceptives. METHODS: The following sera assays
      were obtained: total testosterone (T), free T, weakly bound T,
      dehydroepiandrosterone sulfate, 17 hydroxyprogesterone, estradiol, free thyroxin,
      thyroid stimulating hormone, prolactin, evening cortisol, LH and FSH. RESULTS:
      The total testosterone was markedly elevated but the free testosterone was normal
      and the free and weakly bound testosterone was the high end of normal. The LH/FSH
      ratio was markedly increased consistent with the ultrasound findings of
      polycystic ovarian syndrome. Vaginal cytology showed a mixed high estrogen/high
      androgen effect and the endometrial thickness was only 5 mm. Twice she failed to
      have menses following progesterone withdrawal. CONCLUSIONS: One hypothesized
      mechanism is that the high testosterone levels even though mostly in the bound
      form inhibited estrogen from causing adequate endometrial development.

PMID- 19860351
TI  - Donor-recipient pairs to evaluate the effect of day 3 embryos having at least six
      blastomeres on pregnancy outcome.
AB  - PURPOSE: To determine if having all embryos transferred with at least six
      blastomeres improves pregnancy rates compared to women having an embryo transfer
      with at least one embryo with less than six cells. METHODS: Donor-recipient pairs
      were used to help remove the confounding effect of egg quality. Four donor
      recipient pair types were evaluated: (1) both donor and recipient had all embryos
      with at least six cells, (2) neither donor nor recipient had all embryos with >
      or =6 cells, (3) donor but not recipient had all > or = six cell embryos, (4)
      recipient but not donor had all embryos with > or = six cells. Combining donor
      and recipients there was a significantly higher pregnancy rate per transfer when
      all embryos had at least six blastomeres (50/92 or 54.3%) vs. the group with at
      least one embryo with <6 cells (46/121 or 38.8%). Similarly the implantation rate
      was significantly higher (37.8% vs. 20.3%). CONCLUSIONS: These data corroborate
      conclusions made by evaluating single embryo transfer in women with diminished
      egg reserve that the presence of at least six blastomeres is associated with a
      better chance of a given embryo to implant

PMID- 19860352
TI  - Effects of endometrial thickness and echogenic pattern on assisted reproductive
      treatment outcome.
AB  - PURPOSE: To assess the effects of endometrial thickness and echogenicity on
      pregnancy and implantation rates in cases using assisted reproductive technology
      (ART). METHODS: We retrospectively analyzed the data of 241 ART cycles performed
      at Istanbul Medical Faculty, Reproductive Endocrinology Unit. The cycles were
      classified into three groups according to ultrasonographic endometrial thickness
      measurements on the day of hCG application; 51 cases (group 1) < or =8 mm, 182
      cases (group 2) between 8-14 mm, and eight cases (group 3) 14 mm. Also the cycles
      were grouped according to endometrial echogenicity as trilaminar, isoechogenic
      and hyperechogenic pattern. RESULTS: There was no significant difference in
      pregnancy rates between the three endometrial thickness groups and echogenic
      patterns. When conception and non-conception cycles were compared, no significant
      difference in endometrial thickness was observed (9.88 +/- 1.83 mm vs 9.84 +/-
      1.89 mm). CONCLUSION: Ultrasonographic evaluation of endometrial thickness and
      pattern is not useful in predicting implantation and conception rates in ART
      cycles.

PMID- 19860354
TI  - Conventional oocyte insemination may result in a better pregnancy outcome than
      intracytoplasmic sperm injection (ICSI) for unexplained infertility.
AB  - PURPOSE: To determine in cases of unexplained infertility whether conventional
      oocyte insemination vs. intracytoplasmic sperm injection results in differences
      in fertilization rates, frequency of failed fertilization, clinical and live
      delivered pregnancy rates, and implantation rates. METHODS: Retrospective
      evaluation of these parameters in couples undergoing in vitro fertilization
      embryo transfer (IVF-ET) (minimum 2 embryos) in women with unexplained
      infertility over a 7-year period. RESULTS: There was a significantly higher
      fertilization rate (p < .001) with ICSI vs. conventional insemination (73.7% vs.
      63.7%). However of greater clinical importance, the clinical and live delivered
      pregnancy rates were significantly higher with conventional insemination (52.7%
      and 46.2%) than with ICSI 33.6% and 29.0%. The implantation rates were also
      significantly higher with conventional oocyte insemination (24.9% vs. 17.8%).
      Failed fertilization was low in both groups. CONCLUSION: The process of ICSI,
      whether it involves possible subtle oocyte damage by the procedure or the
      andrologist not choosing the ideal sperm, may lead to embryos that are less
      hearty despite their normal appearance.

PMID- 19860353
TI  - The effect of cetrorelix vs. ganirelix on pregnancy outcome using minimal
      gonadotropin stimulation in women with elevated day 3 serum follicle stimulating
      hormone levels.
AB  - PURPOSE: To determine if the choice of gonadotropin releasing hormone antagonist
      influences subsequent pregnancy rates in women with diminished egg reserve.
      METHOD: Retrospective determination of pregnancy rates following embryo transfer
      in women with day 3 FSH >12 mIU/ml using lower dose gonadotropin stimulation
      regimen. RESULTS: Though no significant differences were found there was a trend
      for lower pregnancy rates with ganirelix vs cetrorelix. CONCLUSIONS: The trend
      for lower pregnancy rates with ganirelix vs. cetrorelix seen in women with
      diminished egg reserve is consistent with the findings of a study performed in
      women with normal egg reserve using a normal gonadotropin stimulation regimen. It
      is not clear if the adverse effect is on the endometrium or the embryo.

PMID- 19860355
TI  - Comparison of the efficacy of selecting sperm with normal nuclei by high
      magnification for intracytoplasmic sperm injection (ICSI) according to age in
      refractory in vitro fertilization (IVF) cases.
AB  - PURPOSE: To determine the pregnancy rates according to age in women failing to
      conceive after three previous embryo transfers or having a husband whose sperm
      shows a DNA fragmentation index (DFI) > 30% when performing the sperm chromatin
      structure assay. METHODS: Women up to age 45 were included and there was no
      restriction for low egg reserve. Live delivered pregnancy rates were determined
      according to three age groups: < or =34, 35-38, 39-45. The data were also
      analyzed in a group comparable to previous publications using high magnification
      ICSI, i.e., younger women with normal egg reserve. Pregnancy rates following
      frozen embryo transfer were also evaluated. RESULTS: Using all 86 in vitro
      fertilization-embryo transfer (IVF-ET) cycles the live delivered pregnancy rates
      were 40% (10/25) for women < or = age 34, 24% (6/25) in women age 35-38, and
      13.8% in women aged 39-45. Evaluating the younger group with normal egg reserve
      with > or =3 previous failed IVF-ET cycles the live delivered pregnancy rate per
      transfer was 38% (16/42). If one adds the additional six live deliveries from
      subsequent frozen embryo transfer (6 of 17, 35.3%) this group of women had a
      52.3% (22/42) live delivered pregnancy rate from one egg retrieval. CONCLUSIONS:
      These data were uncontrolled and thus conclusions should be viewed with caution.
      The results are sufficiently encouraging to warrant a prospective controlled
      trial and possibly encourage a company to consider commercially manufacturing
      high magnification microscopes.

PMID- 19860356
TI  - Successful pregnancy with frozen embryo transfer into a gestational carrier from
      eggs obtained from a woman in premature menopause.
AB  - PURPOSE: To describe a unique case of a successful gestational carrier pregnancy
      in a woman with premature ovarian failure using her own oocyte. METHODS: Despite
      amenorrhea, failure to have menses to progesterone withdrawal and resistance to
      gonadotropin stimulation, ovulation induction was attempted by restoring down
      regulated follicle stimulating hormone (FSH) receptors by lowering the elevated
      serum FSH and allowing stimulation by endogenous or exogenous gonadotropins.
      Oocyte retrieval was attempted if a mature follicle was obtained. GnRH antagonist
      was used to prevent premature oocyte release. Tapering prednisone was used for
      the first five days of the cycle due to patient's history of autoimmune disease
      (vasculitis and Crohn's disease). IVIG was given 8/2003 for vasculitis. RESULTS:
      The patient underwent a total of 19 attempted retrievals during continuous
      natural cycles from 3/2003 to 2/2007. Oocyte retrieval required traversing the
      uterus with the retrieval needle because of ovarian position after multiple
      surgeries for bilateral endometriomas and Crohn's disease. Empty follicle
      syndrome was encountered in four retrieval attempts. In 15 attempts, an oocyte
      was obtained. The sole attempt at natural fertilization failed. ICSI and assisted
      hatching were used in all subsequent attempts, and were successful in all but one
      attempt which led to a 3 pronuclei embryo which was discarded. The first four
      single embryos retrieved (7, 4, 6 cells and morula) were all A1 or A2 and
      transferred fresh to the patient, but no pregnancy resulted. All subsequent
      embryos were cryopreserved. The transfer of four embryos (6-cell and 7-cell and 3
      cell and 8-cell) in two cycles to two different gestational carriers resulted in
      a successful delivery of a full-term healthy female infant 3.3 kg. Genetic
      testing confirmed maternal identity to be the patient, not the carrier.
      CONCLUSIONS: This is the first reported case of a successful gestational carrier
      pregnancy after reversing ovarian failure, inducing ovulation, and transferring a
      frozen-thawed embryo.

PMID- 19860357
TI  - Patient compliance with colposcopy information leaflets.
AB  - OBJECTIVE: To investigate patient satisfaction and compliance with
      recommendations in information leaflets sent to women prior to colposcopy clinic
      attendance and to establish whether alteration to the leaflet improved
      compliance. STUDY DESIGN: Data was collected prospectively and analysed
      retrospectively on the first 50 women attending for colposcopy before and after
      alterations to the information leaflet. RESULTS: All the patients received our
      patient leaflet and over 90% in each group felt that the information was
      understandable, clear and adequate. This is in complete contrast to overall
      compliance of less than 40% in both groups of the women. The first language of
      the patients did not make any major impact on compliance. CONCLUSION: Patients
      understanding of the information provided in the leaflets was not reflected in
      compliance. Compliance was no better in repeat attendees. The compliance with the
      information provided was not affected by the womens first language. Alterations
      in the leaflet did not improve compliance. Other methods of information provision
      should be looked at to try to improve compliance.

PMID- 19860358
TI  - Analysis of federal process of care data reported from hospitals in rural
      westernmost North Carolina.
AB  - OBJECTIVE: To evaluate standardized process of care data collected on selected
      hospitals serving a remote, rural section of westernmost North Carolina.
      MATERIALS & METHODS: Centers for Medicare & Medicaid Services (CMS) data were
      retrospectively analyzed for 21 clinical parameters at Fannin Regional Hospital
      (FRH), Murphy Medical Center (MMC), and Union General Hospital (UGH). A binomial
      test was used to compare each study site to state (NC) and national (U.S.A.)
      average. RESULTS: Summary data showed FRH to have higher scores on a significant
      number of standardized clinical process of care measures compared to state (p <
      0.05) and national (p < 0.005) averages. Too few process of care measures at UGH
      were significantly higher than state and national averages to conclude that
      differences were not due to Type I error. Similarly, at MMC too few process of
      care measures were significantly higher than national averages to conclude that
      observed differences were not attributable to Type I error. MMC did not achieve a
      significantly higher score on any process of care measure when compared to state
      averages. CONCLUSION: Despite limitations associated with summary data analysis,
      the CMS "Hospitals Compare" information suggests that process of care scores at
      FRH are significantly higher than the state and national average. As these
      hospital quality data are freely available to patients, it remains to be
      determined what impact this may have on hospital volume and/or market share in
      this region. Additional research is planned to identify process of care trends in
      this geographical area.

PMID- 19860359
TI  - Role of a non-hormonal oral anti-fibrinolytic hemostatic agent (tranexamic acid)
      for management of patients with dysfunctional uterine bleeding.
AB  - OBJECTIVE: Perimenaposal dysfunctional bleeding is a common complaint seen in
      gynecology clinics. Tranexamic acid is a cheap, over the counter hemostatic agent
      with antifibrinolytic activity that can be used for management of excessive
      menstrual bleeding. However, there are few reports analyzing its effectiveness in
      the management of abnormal menstrual bleeding. This study aimed to evaluate the
      effectiveness of oral transexamic acid treatment in patients with excessive
      dysfunctional perimenopausal menorrhagia. METHOD: One hundred and thirty-two
      consecutive patients with dysfunctional perimenepausal uterine bleeding who were
      admitted to Cankiri Government Hospital between March 2007 and January 2008 were
      prospectively enrolled into this one-sided study. All the patients were asked to
      fill out menstrual diaries and to come to follow-up three months after the
      initial evaluation. All patients took 500 mg of transexamic acid (Transamine 3x2)
      during their menses as the primary treatment and iron preparations if Hb was < 10
      g/dl. The paired sample t-test was used for statistical evaluation. RESULTS: Mean
      age of the patients was 42.8 (range 38-46 yrs). Median bleeding time was nine
      days (range 8-12 days) and median Hb was 10.6 g/dl (range 8.2-11.7) before
      starting the treatment. During follow-up 45 patients were unresponsive to
      transamine and needed further treatments (overall response rate was 65.9%). Among
      responsive patients, after three cycles of transamine usage median bleeding time
      was five days (range 3-8 days) and median Hb values were 12.1 g/dl. CONCLUSION:
      Oral tranexamic acid is a reasonable treatment option for patients with excessive
      dysfunctional perimenopousal bleeding with a 66.0% response rate.

PMID- 19860360
TI  - Disturbed sleep and preterm birth: a potential relationship?
AB  - PURPOSE: Many women report disturbed sleep during pregnancy, but its impact on
      clinical outcomes remains unknown. This study examined subjective sleep quality
      and daytime sleepiness in relation to preterm birth. METHODS: A convenience
      sample of 220 pregnant women completed the Pittsburgh Sleep Quality Index (PSQI),
      the Epworth Sleepiness Scale (ESS), and the Perceived Stress Scale (PSS) during
      the second trimester. Women who had preterm and full-term births were compared on
      these measures. RESULTS: The preterm birth rate of the sample was 14.6%. Sleep
      latency, the period from lights out to sleep onset, was significantly longer in
      the preterm group, which also reported a tendency to use more sleep medications,
      but had lower PSQI daytime dysfunction scores. Perceived stress did not
      differentiate preterm and full-term groups. CONCLUSION: Disturbed sleep in
      pregnancy may be associated with preterm birth. Future studies should examine
      specific physiological factors that underlie this increased vulnerability.

PMID- 19860361
TI  - Albumin/creatinine ratio for prediction of 24-hour albumin excretion of > or =2 g
      in manifest preeclampsia.
AB  - PURPOSE OF INVESTIGATION: To compare whether albumin/creatinine ratios obtained
      from random or 8-hour urine collected in different periods of day differ in
      prediction of albumin excretion > or =2 g in 24-hour urine collection in
      preeclampsia. METHODS: From a total of 70 women, 24-hour urine collected by three
      consecutive periods of eight hours and three random urine samples were taken
      before each period. The variation of albumin-creatinine ratios in samples across
      the day was analyzed by the Friedman and inter-assay coefficient variation. For
      each sample, receiver operator characteristic (ROC) curves were constructed to
      determine an optimal albumin/creatinine ratio value in the prediction of
      albuminuria > or =2 g. RESULTS: The albumin/creatinine ratio did not vary
      significantly over time when all samples pooled. However, there was considerable
      intra-individual variation in both random and timed urine samples. On ROC
      analysis, the albumin/creatinine ratio in both random and timed urine samples
      predicted the 24-hour urine results and there was no difference between samples
      in prediction of albuminuria > or =2 g. A single optimal cut-off point was not
      available between samples. The positive and negative predictive values for
      optimal cut-offs ranged from 48%-88% and 94%-100%, respectively. CONCLUSIONS: The
      random urine albumin/creatinine ratio was a poor predictor for proteinuria a 2 g
      in patients with preeclampsia.

PMID- 19860362
TI  - Mid-trimester maternal serum hCG levels in predicting adverse pregnancy outcome.
AB  - OBJECTIVE: In this prospective study, we investigated the association between mid
      trimester maternal serum human chorionic gonadotropin (ms-hCG) levels and adverse
      pregnancy outcome in a South-Western Greek population. MATERIALS AND METHODS: 130
      healthy Greek women with spontaneous pregnancies were investigated for ms-hCG
      levels between the 13th and 24th weeks of gestation and followed for adverse
      pregnancy outcome, hCG levels > 2.0 multiples of the median value for gestation
      were considered abnormal. Statistical analysis was performed by Pearson's chi
      square test. RESULTS: Gestational complications developed in a total of 12 of the
      130 women studied (9.23%). Elevated ms-hCG levels were detected in a total of 14
      of the 130 women studied (10.77%). CONCLUSION: Multiparameter testing of
      placental function in the mid-trimester (uterine artery Doppler, placental
      morphology and ms-hCG screening) may allow us to identify women with increased
      risk of developing severe placental insufficiency and pregnancy complications.

PMID- 19860363
TI  - An objective method to determinme corneal changes during menopause.
AB  - OBJECTIVE: We hypothesized that menopause has a measurable effect on corneal
      thickness. The aim of this study was to evaluate central corneal thickness (CCT)
      differences between women in the premenopausal and postmenopausal period.
      METHODS: A prospective, case-control, single-blind study was designed. Two groups
      were included: Group I (premenopausal period) and Group II (postmenopausal
      period). Forty women were recruited in each group. The correlation between CCT
      with age, estradiol (E2) and follicle stimulating hormone (FSH) levels were
      evaluated. RESULTS: CCT was significantly decreased in postmenopausal women
      compared to premenopausal women (521.18 +/- 37.97 microm 561 +/- 42.84 microm,
      respectively, p < 0.005). Similarly, there was a linear correlation between CCT
      and serum E2 levels of patients overall (p < 0.01). CONCLUSION: The data
      presented in this study suggest that menopause causes corneal changes, which may
      be documented by central corneal thickness measurement.

PMID- 19860364
TI  - Effectiveness of transvaginal colporrhaphy with porcine acellular collagen matrix
      in the treatment of moderate to severe cystoceles.
AB  - PURPOSE: The aim of this study was to determine the effectiveness of transvaginal
      anterior colporrhaphy with the use of porcine acellular collagen matrix in the
      treatment of moderate to severe cystocele. MATERIALS AND METHODS: This
      retrospective study included 95 patients who underwent anterior colporrhaphy with
      the use of porcine dermus from September 2003 through March 2008 at the
      Gynaecological Department of University General Hospital of Alexandroupolis in
      Greece. The inclusion criterion was a grade 2-4 cystocele by the Baden-Walker
      halfway system. Postoperatively patients were evaluated at one, six and 12
      months. Objective cure was defined as no or grade 1 cystocele with an
      asymptomatic patient at 12 months postoperatively. Improved outcome was
      considered as an asymptomatic patient with a grade 2 cystocele and failure
      symptomatic patients or with grade 3 or 4 cystocele. RESULTS: All of the patients
      had a 12-month postoperative follow-up or were noted as a failure prior to the 12
      month assessment. The majority of the women were menopausal (88.4%) and
      overweight (mean BMI 26.1). The overall cure rate was 81.1%, the improvement of
      the cystocele was 10.5% while the failure rate was 8.4%. The complications we
      noted were vaginal erosion in 2.01% and graft extrusion in 1.05% of the patients.
      CONCLUSION: Transvaginal anterior colporrhaphy using porcine dermal in the
      treatment of moderate to severe cystocele is simple, safe, easily learned and
      performed with a high success rate and low morbidity.

PMID- 19860365
TI  - Uterine myoma in pregnancy: report of 19 patients.
AB  - PURPOSE OF INVESTIGATION: To evaluate the effect of pregnancy on uterine myoma
      and the effect of uterine myoma on the pregnancy prospectively. METHODS:
      Prospective evaluation of 19 pregnant women with uterine myomas was done between
      January 2005 and February 2008 at the Gynecology and Obstetrics Department
      Gaziantep University. The number and changes in size of the uterine myomas during
      pregnancy, and perinatal complications were documented. RESULTS: Totally 37
      fibroids in 19 pregnant women were observed. Neither enlargement of myomas nor
      serious perinatal complications were observed. CONCLUSION: We suggest that in
      contrast with the general opinion there is not much effect of pregnancy on
      uterine myoma size, and most cases are not affected by the presence of uterine
      fibroids resulting in severe perinatal complications. Expectant management may be
      an option for uterine myomas determined before gestation.

PMID- 19860366
TI  - Perceived pain and anxiety before and after amniocentesis among pregnant Turkish
      women.
AB  - PURPOSE OF INVESTIGATION: To examine maternal perception of pain and anxiety
      before and soon after midtrimester genetic amniocentesis. METHODS: Two hundred
      and ninety-two women consecutive were prospectively included in the study between
      March and December 2002. Study variables included age, gestational age,
      gravidity, parity, educational history, history of previous invasive prenatal
      procedures, indication for amniocentesis and source of information regarding
      amniocentesis. Maternal pain and anxiety associated with performing amniocentesis
      were subjectively quantified with the use of the visual analog scale (VAS).
      RESULTS: Actual pain after amniocentesis was significantly lower compared with
      perceived pain before the procedure (3 [0-10] vs. 5 [0-10], p < 0.001). Perceived
      anxiety before amniocentesis was significantly higher than perceived anxiety
      immediately after amniocentesis (7 [0-10] vs. 5 [0-10], p < 0.001). Women who
      were informed about the procedure beforehand perceived the procedure to be less
      painful and expressed less anxiety before and after amniocentesis. CONCLUSIONS:
      Pre-amniocentesis counseling should emphasize that the actual pain and anxiety
      experienced during the procedure are low in intensity and significantly lower
      than expected.

PMID- 19860367
TI  - Ectopic pelvic spleen. Presentation of two cases.
AB  - We present two cases of nulliparous women with ectopic pelvic spleens who were
      hospitalized in our department during the last decade. The clinical and
      laboratory characteristics and the management of such a rare entity are
      discussed.

PMID- 19860368
TI  - Sympathomimetic amine therapy may markedly improve treatment resistant headaches
      related to a vascular permeability defect common in women--presentation of two
      cases.
AB  - PURPOSE: To determine if sympathomimetic amine therapy, which has been effective
      in alleviating pain from various areas of the body in women previously refractory
      to conventional therapy, could help refractory migraine headaches. METHODS: Two
      cases with severe migraines resistant to conventional therapy were evaluated to
      see the response to dextroamphetamine sulfate. RESULTS: Both women dramatically
      responded. Case 1 showed that the treatment benefit is long lasting and not
      merely transient as long as the woman remained on the sympathomimetic amine
      therapy. Case 2 showed that even premenstrual migraines can respond to this
      therapy. CONCLUSIONS: It is not clear if therapy would only benefit women with an
      abnormal water load test or not. To determine if this therapy could be effective
      in refractory headache cases, even in women who pass the water load test, one
      would have to try the dextroamphetamine under similar circumstances and see the
      response. Similarly it is not known if it could help males with refractory
      headaches.

PMID- 19860369
TI  - Extrauterine pregnancy resulting from late spontaneous rupture of an unscarred
      gravid uterus: case report.
AB  - PURPOSE: Rupture of the unscarred grand uterus is a rare obstetric event
      associated with major perinatal mortality and a high incidence of maternal
      mortality and morbidity, particularly peripartum hysterectomy. METHODS & RESULTS:
      We present the case of a primigravida woman who was admitted at 38 weeks of
      gestation complaining of intermittent abdominal pain and vaginal bleeding.
      Although initial evaluation suggested that both mother and fetus were doing well,
      continuous assessment resulted in cesarean section due to variable decelerations
      and increasing abdominal pain. An unexpected abdominal pregnancy was discovered
      resulting from a complete uterine rupture. A healthy infant was delivered and
      hysterectomy was performed. CONCLUSION: Although extrauterine advanced abdominal
      pregnancy resulting from late uterine rupture is associated with high maternal
      and perinatal mortality, a high index of suspicion, close surveillance and
      ultrasonography can achieve good outcome for both mother and infant. We strongly
      believe, that this case report contributes to the insight and further knowledge
      of this rare pregnancy complication.

PMID- 19860370
TI  - Electrochemical assessment of the interaction of dihydrogen phosphate with a
      novel ferrocenyl receptor.
AB  - A novel ferrocene-based amide has been synthesized by condensation reaction and
      characterized by (1)H NMR and UV-vis spectroscopies. The electrochemical
      properties and anion recognition properties of the ferrocene-based amide were
      investigated by the CV and UV-vis techniques. An interesting phenomenon was
      revealed by CV: a second oxidative peak, and the first oxidative peak decreased.
      Therefore, an effective dihydrogen phosphate recognition sensor is expected from
      this compound in the future.

PMID- 19860372
TI  - Effect of adsorbed polymers on bubble--particle attachment.
AB  - The influence of adsorbed dextrin-based polymers on the attachment of a rising
      air bubble to a talc surface has been investigated. Liquid film rupture and
      dynamic contact angle studies have highlighted the major role that adsorbed
      polymers can play in bubble-particle attachment. No direct link was established
      between the equilibrium contact angle of polymer-treated talc surfaces and talc
      flotation recovery. However, clear correlations were observed between the
      flotation recovery of polymer-treated talc and the measured wetting film rupture
      time and rate of dewetting for a bubble attaching to a talc basal plane surface
      treated with the polymers. The retardation of the three-phase contact line
      expansion caused by the adsorbed polymers was found to have the largest influence
      on the bubble-particle attachment. The effect of the morphology (coverage,
      distribution, and shape) of the adsorbed layer on the wetting film rupture and
      the motion of the receding water front is discussed.

PMID- 19860371
TI  - Composition and structural characteristics of humified fractions during the co
      composting process of spent mushroom substrate and wheat straw.
AB  - A spent mushroom substrate (SMS) was mixed with wheat straw (WS) in three
      proportions, C1 (2:1), C2 (4:1), and C3 (6:1), and composted for 90 days in
      static piles with periodic turning to ensure adequate aeration. Samples from each
      pile were collected periodically (after 0, 30, 60, and 90 days), and the humic
      acid-like fractions (HAs) were isolated to determine their elemental composition
      (C, H, N, S, and O), acidic functional group (carboxylic and phenolic) content,
      and structural and functional characteristics using spectroscopic methods
      including ultraviolet-visible, Fourier transform infrared (FTIR), and
      fluorescence. The results of elemental and functional group analyses show that,
      with increasing time of composting, the N, O, and acidic functional group
      contents of HAs increase, whereas their C and H contents and C/N ratio decrease.
      The analysis of FTIR and fluorescence spectra shows that, with increasing
      composting time, the presence of aliphatic and polysaccharide-like structures in
      HAs decreases, whereas oxygenation, polycondensation, and polymerization
      increase. These results suggest that the chemical and structural characteristics
      of the HA fractions in the final composts resemble those typical of native soil
      HAs, which indicate that an adequate degree of maturity and stability is achieved
      after the end of composting. The results of the present study confirm that
      composting is an appropriate treatment to transform fresh organic matter (OM) in
      SMS into humified forms, thus enhancing their quality, agronomic efficiency, and
      environmental safety as a soil OM resource for application as soil amendment.

PMID- 19860373
TI  - Dynamics of a nitroxide layer grafted onto porous silicon.
AB  - This paper reports a rapid electron spin resonance method to assess the dynamical
      properties of spin-labeled alkyl carboxylate layers, covalently linked onto a
      porous silicon substrate. IR and X-ray photoelectron spectroscopy analyses
      complemented the ESR study by proving the successful grafting of the organic
      radical and coverage of the surface.

PMID- 19860374
TI  - Electrochemical, photoelectrochemical, and surface plasmon resonance detection of
      cocaine using supramolecular aptamer complexes and metallic or semiconductor
      nanoparticles.
AB  - Metallic or semiconductor nanoparticles (NPs) are used as labels for the
      electrochemical, photoelectrochemical, or surface plasmon resonance (SPR)
      detection of cocaine using a common aptasensor configuration. The aptasensors are
      based on the use of two anticocaine aptamer subunits, where one subunit is
      assembled on a Au support, acting as an electrode or a SPR-active surface, and
      the second aptamer subunit is labeled with Pt-NPs, CdS-NPs, or Au-NPs. In the
      different aptasensor configurations, the addition of cocaine results in the
      formation of supramolecular complexes between the NPs-labeled aptamer subunits
      and cocaine on the metallic surface, allowing the quantitative analysis of
      cocaine. The supramolecular Pt-NPs-aptamer subunits-cocaine complex allows the
      detection of cocaine by the electrocatalyzed reduction of H(2)O(2). The
      photocurrents generated by the CdS-NPs-labeled aptamer subunits-cocaine complex,
      in the presence of triethanol amine as a hole scavenger, allows the
      photoelectrochemical detection of cocaine. The supramolecular Au-NPs-aptamer
      subunits-cocaine complex generated on the Au support allows the SPR detection of
      cocaine through the reflectance changes stimulated by the electronic coupling
      between the localized plasmon of the Au-NPs and the surface plasmon wave. All
      aptasensor configurations enable the analysis of cocaine with a detection limit
      in the range of 10(-6) to 10(-5) M. The major advantage of the sensing platform
      is the lack of background interfering signals.

PMID- 19860375
TI  - Spectral tuning of conjugated polymer colloid light-emitting diodes.
AB  - In recent years, the importance of the polymer light-emitting diode (PLED) has
      grown immensely, proving very desirable in numerous applications because of very
      high efficiencies, low power consumption, and ease of fabrication. Typically,
      these devices have been constructed in a layered, thin-film fashion consisting of
      either electron- and hole-transport materials doped with a luminescent dye
      (Hebner, T. R.; Sturm, J. C. Appl. Phys. Lett. 1998, 73, 1775. Jiang, X.;
      Register, R. A.; Killeen, K. A.; Thompson, M. E.; Pschenitzka, F.; Hebner, T. R.;
      Sturm, J. C. J. Appl. Phys. 2002, 91, 6717. Yeh, K. M.; Chen, Y. Org. Electron.
      2008, 9, 45-50. Oh, G. C.; Yun, J. J.; Park, S. M.; Son, S. H.; Han, E. M.; Gu,
      H. B.; Jin, S. H.; Yoon, Y. S. Mol. Cryst. Liq. Cryst. 2003, 405, 43-51. Lee, J.
      I.; Chu, H. Y.; Kim, S. H.; Do, L. M.; Zyung, T.; Hwang, D. H. Opt. Mater. 2003,
      21, 205-210. Hwang, D.-H.; Park, M.-J.; Lee, C. Synth. Met. 2005, 152, 205-208)
      or a conjugated polymer that can be engineered to tune the emission of the PLED
      to particular wavelengths. Stable PLED aqueous colloidal dispersions were
      prepared containing poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene],
      (MEH-PPV), poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO), and a binary poly(9,9-di
      n-octylfluorenyl-2,7-diyl)/poly(2,5-dioctyl-1,4-phenylenevinylene) (PFO/POPPV)
      particle dispersion. Red-, green-, and blue-light-emitting colloidal dispersions
      could then be combined to achieve color-tailored emissions spanning the visible
      spectrum.

PMID- 19860376
TI  - Synthetic and structural studies on L-cysteinyl group-containing diiron/triiron
      azadithiolates as active site models of [FeFe]-hydrogenases.
AB  - Five new L-cysteinyl group-containing diiron/triiron azadithiolate complexes (3
      6, 10), which could be regarded as the active site models of [FeFe]-hydrogenases,
      have been successfully synthesized. Treatment of L-cysteinyl sodium mercaptide
      CytSNa (1, Cyt = CH(2)CH(CO(2)Et)NH(CO(2)Bu-t) with complex [(mu
      SCH(2))(2)NCH(2)CH(2)Br]Fe(2)(CO)(6) (2) in THF at room temperature resulted in
      formation of model complex [(mu-SCH(2))(2)NCH(2)CH(2)SCyt]Fe(2)(CO)(6) (3).
      Further treatment of 3 with decarbonylating agent Me(3)NO in MeCN at room
      temperature afforded model complex [(mu-SCH(2))(2)NCH(2)CH(2)SCyt]Fe(2)(CO)(5)
      (4). Similarly, treatment of 3 with an equimolar mixture of Me(3)NO and Ph(3)P
      gave model complex [(mu-SCH(2))(2)NCH(2)CH(2)SCyt]Fe(2)(CO)(5)(Ph(3)P) (5) and
      further treatment of 5 with Me(3)NO produced model complex [(mu
      SCH(2))(2)NCH(2)CH(2)SCyt]Fe(2)(CO)(4)(Ph(3)P) (6). More interestingly, model
      complex [(mu-SCH(2))(2)NCH(CO(2)Et)CH(2)SFe(CO)(2)Cp]Fe(2)(CO)(5) (10) could be
      synthesized by a "one pot" reaction of the in situ prepared (mu
      HS)(2)Fe(2)(CO)(6) (9) with 37% aqueous formaldehyde followed by treatment with
      the N-deprotected L-cysteinyl iron mercaptide Cp(CO)(2)FeSCH(2)CH(CO(2)Et)NH(2)
      (8). Complex 8 is new, which was prepared by treatment of complex Cp(CO)(2)FeSCyt
      (7) with CF(3)CO(2)H followed by 25% aqueous NH(3). All the new complexes 3-6, 8,
      and 10 were characterized by elemental analysis and various spectroscopic
      techniques, whereas complexes 5 and 10 were further characterized by X-ray
      crystallography.

PMID- 19860377
TI  - Nitrate and perchlorate complexes of uranium(IV).
AB  - The solid-state structures of the [U(IV)(NO(3))(6)](2-) anions in the [n
      Pr(4)N](2)[U(NO(3))(6)] (1), [n-Bu(4)N](2)[U(NO(3))(6)] (2), and
      [Ph(4)P](2)[U(NO(3))(6)] x 4 NCCH(3) (3) salts were determined using single
      crystal X-ray diffraction. For the first time, a nondisordered structure of the
      hexanitratouranate(IV) dianion with a coordination number of 12 for the central
      U(IV) atom was determined. Salts 1-3 were prepared in simple metathesis reactions
      and characterized using IR spectroscopy, C/H/N analysis, and single-crystal X-ray
      diffraction. Attempts to prepare a salt containing the [U(IV)(ClO(4))(6)](2-)
      anion using the analogous route resulted in the isolation of
      U(ClO(4))(4)(NCCH(3))(5) (4), which was characterized using single-crystal X-ray
      diffraction. Compound 4 is the first structurally characterized uranium(IV)
      perchlorate to be reported in the literature.

PMID- 19860378
TI  - Unprecedent isolation of a mixture of conformational and linkage isomers in a
      thiosemicarbazone cobalt mesocate.
AB  - A cobalt(II) thiosemicarbazonate mesocate has been structurally characterized as
      an unexpected mixture of conformational and linkage isomers. Moreover, we have
      shown that the absence of a nitrogen atom in the spacer of the helicand ligand
      H(2)L(a), enables the assembly of an achiral mesohelical complex in the case of
      Co(II) ions.

PMID- 19860379
TI  - Functional silanes as surface modifying primers for the preparation of highly
      stable and well-defined magnetic polymer hybrids.
AB  - A general and versatile method for the functionalization and subsequent
      modification of single dispersed magnetite nanoparticles by direct reaction of
      alkoxysilanes on the particle surface is reported. Our data supports the
      formation of a dense monolayer that is controlled by sterical needs. By selecting
      the functionality of alkoxysilanes, the surface properties of the particles can
      be tailored. Depending on the surface functionality, the modified particles can
      be used as macrocomonomers or macrocrosslinkers, or as macroinitiators for
      surface-initiated polymerization and thus enable the covalent attachment of
      polymers.

PMID- 19860380
TI  - Study on the combined effects of solvent evaporation and polymer flow upon block
      copolymer self-assembly and alignment on topographic patterns.
AB  - Microphase separation of a polystyrene-block-polyisoprene-block-polystyrene
      triblock copolymer thin film under confined conditions (i.e., graphoepitaxy)
      results in ordered periodic arrays of polystyrene cylinders aligned parallel to
      the channel side-wall and base in a polyisoprene matrix. Polymer orientation and
      translational ordering with respect to the topographic substrate were elucidated
      by atomic force microscopy (AFM) while film thickness and polymer profile within
      the channel were monitored by cross-sectional transmission electron microscopy
      (TEM) as a function of time over a 6 h annealing period at 120 degrees C. Upon
      thermal annealing, the polymer film simultaneously undergoes three processes:
      microphase separation, evaporation of trapped solvent, and mass transport of
      polymer from the mesas into the channels. A significant volume of solvent is
      trapped within the polymer film upon spin coating arising from the increased
      polymer/substrate interfacial area due to the topographic pattern. Mass transport
      of polymer during this process results in nonuniform films, where subtle changes
      in the film thickness within the channel have profound effects on the microphase
      separation process. The initially disordered structure within the film underwent
      an orientation transition via an intermediate formation of perpendicular
      cylinders (nonequilibrium) to a parallel (equilibrium) orientation with respect
      to the channel base. Herein, we present a time-resolved study of the cylinder
      reorientation process detailing how changing film thickness during the annealing
      process dramatically affects both the local and lateral orientation of the
      observed structure. Finally, a brief mathematical model is provided to evaluate
      spin coating over a complex topography following a classical asymptotic
      approximation of the Navier-Stokes equations for the as-deposited films.

PMID- 19860384
TI  - Efficient formal total synthesis of the erythrina alkaloid (+)-erysotramidine,
      using a domino process.
AB  - A domino process consisting of an amidation, spirocyclization, and formation of
      an iminium ion and electrophilic aromatic substitution of a phenylethylamine and
      a ketoester leads to the spirocyclic skeleton of (+)-erysotramidine, which can be
      further transformed into the natural alkaloid.

PMID- 19860383
TI  - Constituents of Polyalthia longifolia var. pendula.
AB  - Three new clerodane-type diterpenes, 6alpha,16-dihydroxycleroda-3,13-dien-15-oic
      acid (1), 6alpha,16-dihydroxycleroda-4(18),13-dien-15-oic acid (2), and
      4alpha,18beta-epoxy-16-hydroxyclerod-13-en-15-oic acid (3), and four new
      protoberberine alkaloids, (-)-8-oxo-10-hydroxy-2,3,9-trimethoxyberberine (4), (-)
      8-oxo-2,11-dihydroxy-3,10-dimethoxyberberine (5), (-)-8-oxo-11-hydroxy-2,3,9,10
      tetramethoxyberberine (6), and (-)-8-oxo-2,10-dihydroxy-3,9,11
      trimethoxyberberine (7), together with 11 known substances, were isolated from a
      methanol extract of the stems of Polyalthia longifolia var. pendula. The
      structures of 1-7 were elucidated on the basis of spectroscopic data analysis.
      Compounds were evaluated for their antiproliferative activities against A549 and
      MCF-7 cancer cells, and among the substances tested, only 16-oxo-cleroda-3,13
      dien-15-oic acid (8) exhibited cytotoxicity.

PMID- 19860382
TI  - A semi-synthetic ion channel platform for detection of phosphatase and protease
      activity.
AB  - Sensitive methods to probe the activity of enzymes are important for clinical
      assays and for elucidating the role of these proteins in complex biochemical
      networks. This paper describes a semi-synthetic ion channel platform for
      detecting the activity of two different classes of enzymes with high sensitivity.
      In the first case, this method uses single ion channel conductance measurements
      to follow the enzyme-catalyzed hydrolysis of a phosphate group attached to the C
      terminus of gramicidin A (gA, an ion channel-forming peptide) in the presence of
      alkaline phosphatase (AP). Enzymatic hydrolysis of this phosphate group removes
      negative charges from the entrance of the gA pore, resulting in a product with
      measurably reduced single ion channel conductance compared to the original gA
      phosphate substrate. This technique employs a standard, commercial bilayer setup
      and takes advantage of the catalytic turnover of enzymes and the amplification
      characteristics of ion flux through individual gA pores to detect picomolar
      concentrations of active AP in solution. Furthermore, this technique makes it
      possible to study the kinetics of an enzyme and provides an estimate for the
      observed rate constant (k(cat)) and the Michaelis constant (K(M)) by following
      the conversion of the gA-phosphate substrate to product over time in the presence
      of different concentrations of AP. In the second case, modification of gA with a
      substrate for proteolytic cleavage by anthrax lethal factor (LF) afforded a
      sensitive method for detection of LF activity, illustrating the utility of ion
      channel-based sensing for detection of a potential biowarfare agent. This ion
      channel-based platform represents a powerful, novel approach to monitor the
      activity of femtomoles to picomoles of two different classes of enzymes in
      solution. Furthermore, this platform has the potential for realizing
      miniaturized, cost-effective bioanalytical assays that complement currently
      established assays.

PMID- 19860385
TI  - Synthesis of the bicyclic welwitindolinone core via an alkylation/cyclization
      cascade reaction.
AB  - Synthesis of an advanced welwitindolinone intermediate via an
      alkylation/cyclization reaction is reported. The key step involves a one pot
      Lewis acid-mediated alkylation of a silylketene aminal with a furan alcohol
      followed by an intramolecular cyclization. The reaction is stereoselective and
      takes place at low temperature. The cycloadduct was highly functionalized and
      contains the welwitindolinone core structure.

PMID- 19860386
TI  - Azafullerene-like nanosized clusters.
AB  - Carbon nitride materials have extraordinary potential in various applications,
      including catalysts, filled-particles, and superhard materials. Carbon nitride
      nanoclusters have been prepared under mild solvothermal conditions by a reaction
      between 1,3,5-trichlotriazine and sodium azide in toluene. The bulk material
      formed has a C(3)N(4) composition and consists of spheres with diameters ranging
      from approximately 1 nm to 4 mum. Nanometer-sized clusters of C(3)N(4)
      stoichiometry have been isolated on surfaces by sublimation or simple
      physicochemical methods. The clusters have then been characterized by atomic
      force microscopy and X-ray photoelectron spectroscopy. The laser desorption
      ionization mass spectra show peaks assignable to the C(12)N(16), C(21)N(28), and
      C(33)N(44) molecules which could correspond to cage structures with 4, 7, and 11
      units of the C(3)N(4) subunit, respectively. The structure and stability of these
      new nitrogen-rich carbon nitride nanocages has been investigated using density
      functional theory calculations.

PMID- 19860387
TI  - A one-pot, base-free annelation approach to alpha-alkylidene-gamma
      butyrolactones.
AB  - A novel annelation procedure has been developed for the conversion of gamma
      hydoxy enones into alpha-alkylidene-gamma-butyrolactones. This one-pot method
      utilizes the Bestmann ylide (triphenylphosphoranylideneketene) and proceeds by
      way of acylation followed by an intramolecular conjugate addition/proton
      transfer/Wittig olefination sequence. The procedure is "base-free" and is useful
      for the preparation of a range of alpha-alkylidene-gamma-butyrolactones including
      alpha-methylene-gamma-butyrolactone examples, which can be particularly base
      sensitive.

PMID- 19860388
TI  - Polyaza cryptand receptor selective for dihydrogen phosphate.
AB  - A hexaamine cage with pyridyl spacers was synthesized in good yield by a [2+3]
      Schiff-base condensation followed by sodium borohydride reduction. The
      protonation constants of the receptor as well as its association constants with
      Cl(-), NO(3)(-), AcO(-), ClO(4)(-), SO(4)(2-), H(2)PO(4)(-), and H(2)AsO(4)(-)
      were determined by potentiometry at 298.2 +/- 0.1 K in H(2)O/MeOH (50:50 v/v) and
      at ionic strength 0.10 +/- 0.01 M in KTsO. These studies revealed that although
      dihydrogen phosphate is less charged than sulfate, it is still appreciably bound
      by the receptor at low pH, suggesting that the pyridyl nitrogen is accepting
      hydrogen bonds from dihydrogen phosphate. It is also shown that dihydrogen
      phosphate is capable of effectively competing with sulfate for the receptor at
      higher pH, being selective for hydrogen phosphate at pH about 7.0. (31)P NMR
      experiments supported these findings. The fact that the receptor shows such a
      marked preference for hydrogen phosphate based mainly in its hydrogen bond
      accepting/donating ability in a highly competitive medium such as water/methanol
      mixed solvent is quite remarkable. Single-crystal X-ray diffraction
      determinations of anion associations between H(6)pyr(6+) receptor and nitrate,
      sulfate, and phosphate are consistent with the existence of
      [(H(6)pyr)(NO(3))(3)(H(2)O)(3)](3+), [(H(6)pyr)(SO(4))(2)(H(2)O)(4)](2+), and
      [(H(6)pyr)(HPO(4))(2)(H(2)PO(4))(H(2)O)(2)](+) cations. One nitrate anion is
      embedded into the H(6)pyr(6+) cage of the first supermolecule whereas in the
      second and third ones the anions are located in the periphery of the
      macrobicycle.

PMID- 19860389
TI  - Concise route to the chiral pyrrolidine core of selective inhibitors of neuronal
      nitric oxide.
AB  - 2-(((3R,4R)-4-(Allyloxy)-1-benzylpyrrolidin-3-yl)methyl)-6-(2,5-dimethyl-1H
      pyrrol-1-yl)-4-methylpyridine (2), a key intermediate for the preparation of
      novel neuronal nitric oxide synthase (nNOS) inhibitors, is synthesized using
      diisopropyl (R)-(+)-malate as the starting material. The key steps involve a
      Frater-Seebach diastereoselective alkylation and a fast intramolecular
      cyclization.

PMID- 19860390
TI  - A noninvasive thin film sensor for monitoring oxygen tension during in vitro cell
      culture.
AB  - Oxygen tension in mammalian cell culture can profoundly affect cellular
      differentiation, viability, and proliferation. However, precise measurement of
      dissolved oxygen in real time remains difficult. We report a new noninvasive
      sensor that can accurately measure oxygen concentration during cell culture while
      being compatible with live-cell imaging techniques such as fluorescence and phase
      contrast microscopy. The sensor is prepared by integrating the porphyrin dye,
      Pt(II) meso-tetrakis(pentafluorophenyl)porphine (PtTFPP) into
      polydimethylsiloxane (PDMS) thin films. Response of the sensor in the presence of
      oxygen can be characterized by the linear Stern-Volmer relationship with high
      sensitivity (K(SV) = 584 +/- 71 atm(-1)). A multilayer sensor design, created by
      sandwiching the PtTFPP-PDMS with a layer of Teflon AF followed by a second PDMS
      layer, effectively mitigates against dye cytotoxicity while providing a substrate
      for cell attachment. Using this sensor, changes in oxygen tension could be
      monitored in real-time as attached cells proliferated. The oxygen tension was
      found to decrease due to oxygen consumption by the cells, and the data could be
      analyzed using Fick's law to obtain the per-cell oxygen consumption rate. This
      sensor is likely to enable new studies on the effects of dissolved oxygen on
      cellular behavior.

PMID- 19860391
TI  - Bronsted acid-promoted hydrocyanation of arylalkenes.
AB  - Nonactivated arylalkenes are effectively converted to tertiary benzylic nitriles
      in the presence of triflic acid and trimethylsilyl cyanide. The hydrocyanation
      reactions result in good to excellent yield when electron-donating groups are
      substituted on the benzene ring. The reaction conditions are mild and relatively
      safe, notably without need for handling hazardous hydrogen cyanide gas, providing
      simple and easy access to tertiary benzylic nitriles. The reaction was applied to
      the preparation of a PDE4 inhibitor (3) as well as a series of analogues.

PMID- 19860392
TI  - A modular synthesis of alkynyl-phosphocholine headgroups for labeling
      sphingomyelin and phosphatidylcholine.
AB  - A general route to phospho- and sphingolipids that incorporate an alkyne in the
      phosphocholine headgroup is described. The strategy preserves the ammonium
      functionality of the phosphocholine and can be easily modified to introduce
      desired functional groups at the N-acyl chain. The targets accessible with this
      strategy provide a bioorthogonal handle for postsynthetic introduction of
      fluorophores or other labeling agents with aqueous phase chemistry. We report the
      synthesis of sphingomyelin derivatives that incorporate a fluorophore and an
      alkyne. The modified sphingolipids retain activity as substrates for
      sphingomyelinase, making these compounds viable probes of enzymatic activity.
      Importantly, the strategy allows modification of the lipid across the
      phosphodiester, making the alkyne a potential probe of sphingomyelinase activity.

PMID- 19860393
TI  - Zinc chloride-promoted aryl bromide-alkyne cross-coupling reactions at room
      temperature.
AB  - Substoichiometric amounts of ZnCl(2) promote the room temperature, Pd/P(t-Bu)(3)
      catalyzed cross-coupling of aryl bromides with alkynes. Pd(I) dimer 1 is
      demonstrated to be a particularly active precatalyst for this reaction. The
      reaction is general for a wide variety of aryl bromides.

PMID- 19860394
TI  - One-pot facile synthesis of substituted isoindolinones via an Ugi four-component
      condensation/Diels-Alder cycloaddition/ deselenization-aromatization sequence.
AB  - A versatile one-pot synthesis of substituted isoindolinones from 2-furaldehydes,
      amines, 2-(phenylselanyl)acrylic acids, and isocyanides is described. The tandem
      process involves the Ugi four-component condensation, intramolecular Diels-Alder
      cycloaddition, and subsequent deselenization-aromatization promoted by BF(3)
      OEt(2). The procedure is general and efficient and the substrates are easily
      available.

PMID- 19860395
TI  - Circularly polarized luminescence of Eu(III) complexes with point- and axis
      chiral ligands dependent on coordination structures.
AB  - Circularly polarized luminescence (CPL) of Eu(III) complexes with point- and axis
      chiral ligands, [Eu((R/S)-BINAPO)(D-facam)(3)] ((R/S)-BINAPO, (R/S)-2,2'
      bis(diphenylphosphoryl)-1,1'-binaphthyl; D-facam, 3-trifluoroacetyl-d-camphor),
      [Eu(BIPHEPO)(D-facam)(3)] (BIPHEPO, 2,2'-bis(diphenylphosphoryl)-biphenyl),
      [Eu(TPPO)(2)(D-facam)(3)] (TPPO, triphenylphosphine oxide), and [Eu((R)
      BINAPO)(hfa)(3)] (hfa, 1,1,1,5,5,5-hexafluoropentane-2,4-dione) are reported. The
      photophysical properties of chiral Eu(III) complexes were characterized by
      circular dichroism spectra, emission spectra, emission quantum yields, emission
      lifetimes, and CPL spectra. The dissymmetry factors of their CPL (|g(CPL)|) at
      the magnetic-dipole transition of [Eu((R)-BINAPO)(D-facam)(3)], [Eu((S)-BINAPO)(D
      facam)(3)], [Eu(BIPHEPO)(D-facam)(3)], and [Eu(TPPO)(2)(D-facam)(3)] were as high
      as 0.44, 0.34, 0.24, and 0.47, respectively, while [Eu((R)-BINAPO)(hfa)(3)]
      exhibited a relatively smaller dissymmetry factor (|g(CPL)| = 0.03). Their
      coordination structures were determined by the X-ray single-crystal analyses with
      shape-measure estimations. The photophysical relationship between the CPL
      properties and the electric transition probabilities of the chiral Eu(III)
      complexes is elucidated in terms of the coordination structures.

PMID- 19860396
TI  - 3,3'-Anisyl-substituted BINOL, H(4)BINOL, and H(8)BINOL ligands: asymmetric
      synthesis of diverse propargylic alcohols and their ring-closing metathesis to
      chiral cycloalkenes.
AB  - A series of optically active BINOL, H(4)BINOL, and H(8)BINOL derivatives were
      prepared. These compounds in combination with ZnEt(2) and Ti(O(i)Pr)(4) were used
      to catalyze the asymmetric reaction of alkynes with aldehydes to generate chiral
      propargylic alcohols at room temperature. Through this comparative study, a 3,3'
      bisanisyl-substituted H(8)BINOL (S)-7 was found to be a generally
      enantioselective catalyst for the reaction of structurally diverse terminal
      alkynes with a variety of aldehydes. It catalyzed the reactions of alkyl
      propiolates with 88-99% ee; the reactions of phenylacetylene with 81-87% ee; the
      reactions of 4-phenyl-1-butyne, an alkyl alkyne, with 77-89% ee; and the
      reactions of trimethylsilylacetylene with 92-97% ee. The optically active
      propargylic alcohols generated from this catalytic asymmetric alkyne addition
      were observed to undergo efficient ring-closing-metathesis (RCM) reaction in the
      presence of the Grubbs II catalyst to produce chiral cycloalkenes. It was further
      found that some of the chiral propargylic alcohols underwent a highly
      chemoselective tandem RCM hydrogenation reaction with retention of the
      enantiomeric purity.

PMID- 19860397
TI  - A general synthesis of macrocyclic pi-electron-acceptor systems.
AB  - Cyclocondensations of aromatic diamines with 1,1'-bis(2,4-dinitrophenyl)-4,4'
      bipyridinium salts afford doubly or quadruply charged, macrocyclic, N,N'
      diarylbipyridinium cations. These are tolerant of a wide range of acids, bases,
      and nucleophiles, although they appear to undergo reversible, one-electron
      reduction by tertiary amines. Single-crystal X-ray analysis demonstrates the
      presence of a macrocycle conformation in which the 4,4'-bipyridinium and 4,4'
      biphenylenedisulfonyl residues are suitably spaced and aligned for complexation
      with pi-donor arenes, and NMR studies in solution indeed confirm binding to 1,5
      bis[hydroxy(ethoxy)ethoxy]naphthalene.

PMID- 19860399
TI  - Efficient chemoenzymatic dynamic kinetic resolution of 1-heteroaryl ethanols.
AB  - The scope and limitation of the combined ruthenium-lipase induced dynamic kinetic
      resolution (DKR) through O-acetylation of racemic heteroaromatic secondary
      alcohols, i.e., 1-heteroaryl substituted ethanols, was investigated. After
      initial screening of reaction conditions, Candida antarctica lipase B (Novozyme
      435, N435) together with 4-chloro-phenylacetate as acetyl-donor for kinetic
      resolution (KR), in conjunction with the ruthenium-based Shvo catalyst for
      substrate racemization in toluene at 80 degrees C, enabled DKR with high yields
      and stereoselectivity of various 1-heteroaryl ethanols, such as oxadiazoles,
      isoxazoles, 1H-pyrazole, or 1H-imidazole. In addition, DFT calculations based on
      a simplified catalyst complex model for the catalytic (de)hydrogenation step are
      in agreement with the previously reported outer sphere mechanism. These results
      support the further understanding of the mechanistic aspects behind the
      difference in reactivity of 1-heteroaryl substituted ethanols in comparison to
      reference substrates, as often referred to in the literature.

PMID- 19860400
TI  - Wet-spinning of regenerated silk fiber from aqueous silk fibroin solution:
      discussion of spinning parameters.
AB  - Regenerated silk fibroin (RSF) fibers were obtained by extruding a concentrated
      aqueous silk fibroin solution into an ammonium sulfate coagulation bath. A custom
      made simplified industrial-type wet-spinning device with continuous mechanical
      postdraw was used. The effect of dope concentration, coagulation bath, extrusion
      rate, and postdraw treatment on the morphology of RSF fiber was examined. The
      results showed that although RSF fiber could be formed with dope concentration
      between 13 and 19% (w/w), the ones spun from 15% RSF solution showed the most
      regular morphology being dense and homogeneous in cross-section with a smooth
      surface and a uniform cylindrical shape. Though it had little effect on
      morphology, postdraw treatment especially under steam, significantly improved the
      mechanical properties of the RSF fibers.

PMID- 19860401
TI  - Size-focusing synthesis, optical and electrochemical properties of monodisperse
      Au38(SC2H4Ph)24 nanoclusters.
AB  - We report a facile, high yielding synthetic method for preparing truly
      monodisperse Au(38)(SC(2)H(4)Ph)(24) nanoclusters. The synthetic approach
      involves two main steps: first, glutathionate (-SG) protected polydisperse Au(n)
      clusters (n ranging from 38 to approximately 102) are synthesized by reducing
      Au(I)-SG in acetone; subsequently, the size-mixed Au(n) clusters react with
      excess phenylethylthiol (PhC(2)H(4)SH) for approximately 40 h at 80 degrees C,
      which leads to Au(38)(SC(2)H(4)Ph)(24) clusters of molecular purity. Detailed
      studies by mass spectrometry and UV-vis spectroscopy explicitly show a gradual
      size-focusing process occurred in the thermal etching-induced growth process. The
      formula and molecular purity of Au(38)(SC(2)H(4)Ph)(24) clusters are confirmed by
      electrospray ionization (ESI) and matrix-assisted laser desorption ionization
      (MALDI) mass spectrometry, and size-exclusion chromatography. The optical and
      electrochemical properties of Au(38)(SC(2)H(4)Ph)(24) clusters show molecule-like
      behavior and the HOMO-LUMO gap of the cluster was determined to be approximately
      0.9 eV. The size focusing growth process is particularly interesting and may be
      exploited to synthesize other robust gold thiolate clusters.

PMID- 19860402
TI  - Regioselective amination of carbaporpholactone and N-confused porphyrin.
AB  - An efficient route to the direct amination at the inner carbon of
      carbaporpholactone is reported. A regioselectivity of substitution is enforced by
      activation of the embedded furanone fragment due to coordination of the highly
      oxidized silver(III) cation. A stepwise oxidation of the dimethylamine derivative
      leads to the internally bridged carbaporpholactones which contain respectively
      [5.7.5] tricyclic or [5.7.5.7.5] pentacyclic rings. The analogous reactivity of N
      confused porphyrin has been also explored.

PMID- 19860403
TI  - Geometry dependence of the ring-opening E2 reaction in lactones.
AB  - Gas phase bimolecular elimination reactions (E2) of lactones, with and without
      alkyl substitution on the omega carbon, have been studied. The comparison between
      the substituted and corresponding unsubstituted lactones reveals, without
      complications from ring strain, the effect of geometric distortion from the
      periplanar geometry preferred for E2 reactions. The four- and five-membered ring
      lactones show a significant effect from the distortion, while the six- and seven
      membered rings show relatively little. The geometric distortion is clearly much
      more important than the ring strain. The kinetic energy dependence of the E2
      reaction as well as the proton transfer reaction between fluoride and a partially
      deuterated delta-valerolactone has also been investigated.

PMID- 19860404
TI  - Tricationic porphyrin conjugates: evidence for chain-structure-dependent
      relaxation of excited singlet and triplet States.
AB  - Conjugates of 5-(4-carboxyphenyl)-10,15,20-tris(4-methylpyridinium-4-yl)porphyrin
      (P-H) are promising photoactive agents for medical applications. As their
      ultimate efficacy will depend on the behavior of initial excited states,
      photophysical parameters have been determined with conventional steady-state
      absorption and fluorescence as well as time-resolved femto- and nanosecond
      spectroscopies. The fluorescence quantum yield of P-H and P-H conjugated to
      uncharged groups increases from approximately 0.03 in pH 7 buffer to
      approximately 0.05 in Triton X100 micelles (TX100) and in ethanol and to 0.12 in
      sodium dodecyl sulfate (SDS) micelles. Corresponding (1)S(1) lifetimes are
      approximately 5-10 ns. In buffer, an equilibrium between P-H monomers and small
      size aggregates is observed. Conjugation with poly-S-lysine (P-(Lys)(n)) results
      in fluorescence quenching in all solvents. Structural reorganization of
      conjugates bearing a Di-O-isopropylidene-alpha-d-galactopyranosyl or a alpha/beta
      d-galactopyranosyl group occurs in ethanol (k approximately 0.15 ps(-1)) after
      (1)S(1) state solvation (approximately 700 fs). Relaxation of bulky P-(Lys)(n)
      polypeptide chains takes place on a longer time scale in all solvents (k <or=
      0.01 ps(-1)) with enhanced internal conversion. Triplet state ((3)T(1)) transient
      spectra of all derivatives in PBS, SDS, TX100, and ethanol exhibit a strong
      absorbance with a broad maximum in the 460-475 nm region and minor maxima at
      approximately 540, 630, and 690 nm. In ethanol, energy transfer from the P-H
      (3)T(1) state to beta-carotene provides an estimate of epsilon approximately
      40,000 M(-1) cm(-1) at 460 nm for the P-H (3)T(1) state. Using triplet meso
      tetraphenylporphyrin as an actinometer, the P-H triplet quantum yield (Phi(T)) is
      estimated to be approximately 0.50 in all solvents. This high Phi(T) leads to
      effective singlet oxygen production in buffered solutions.

PMID- 19860406
TI  - Transfer-free batch fabrication of single layer graphene transistors.
AB  - Full integration of graphene into conventional device circuitry would require a
      reproducible large scale graphene synthesis that is compatible with conventional
      thin film technology. We report the synthesis of large scale single layer
      graphene directly onto an evaporated copper film. A novel fabrication method was
      used to directly pattern these graphene sheets into devices by simply removing
      the underlying copper film. Raman and conductance measurements show that the
      mechanical and electrical properties of our single layer graphene are uniform
      over a large area, ( Ferrari, A. C. et al. Phys. Rev. Lett. 2006, 97, 187401.)
      which leads to a high device yield and successful fabrication of ultra long (>0.5
      mm) graphene channels. Our graphene based devices present excellent electrical
      properties including a promising carrier mobility of 700 cm(2)/V.s and current
      saturation characteristics similar to devices based on exfoliated graphene (
      Meric, I.. et al. Nat Nanotechnol. 2008, 3, 654-659).

PMID- 19860407
TI  - Experimental evidence for the all-up reactive conformation of chiral rhodium(II)
      carboxylate catalysts: enantioselective synthesis of cis-cyclopropane alpha-amino
      acids.
AB  - Useful empirical insights onto the enantioinduction process of chiral Rh(II)
      carboxylate catalysts are described in the first catalytic asymmetric
      cyclopropanation of alkenes with alpha-nitro diazoacetophenones. X-ray, solution
      NMR, and reactivity studies made on these complexes suggest that the level of
      asymmetric induction strongly depends on their active symmetry, which in turn
      relies on the nature of the chiral ligands' substituents. The catalyst's 'All Up'
      reactive conformation resulted in being necessary to obtain good
      stereoselectivity, and the resulting products are shown to be key intermediates
      in a concise synthesis of highly enantioenriched cis-cyclopropane alpha-amino
      acids.

PMID- 19860408
TI  - Cycloisomerization of aromatic homo- and bis-homopropargylic alcohols via
      catalytic Ru vinylidenes: formation of benzofurans and isochromenes.
AB  - Ru-catalyzed cycloisomerizations of aromatic homo- and bis-homopropargylic
      alcohols effectively afford benzofurans and isochromenes. These processes proved
      to be chemo- and regioselective (5-, and 6-endo cyclizations) derived from key Ru
      vinylidene intermediates. The presence of an amine/ammonium base-acid pair is
      crucial for the catalytic cycle.

PMID- 19860410
TI  - "Hairy" poly(3-hexylthiophene) particles prepared via surface-initiated Kumada
      catalyst-transfer polycondensation.
AB  - Herein, we present a new paradigm in the engineering of nanostructured hybrids
      between conjugated polymer and inorganic materials via a chain-growth surface
      initiated Kumada catalyst-transfer polycondensation (SI-KCTP) from particles.
      Poly(3-hexylthiophene), P3HT, a benchmark material for organic electronics, was
      selectively grown by SI-KCTP from (nano)particles bearing surface-immobilized Ni
      catalysts supported by bidentate phosphorus ligands, that resulted in hairy
      (nano)particles with end-tethered P3HT chains. Densely grafted P3HT chains
      exhibit strongly altered optical properties compared to the untethered
      counterparts (red shift and vibronic fine structure in absorption and
      fluorescence spectra), as a result of efficient planarization and chain
      aggregation. These effects are observed in solvents that are normally recognized
      as good solvents for P3HT (e.g., tetrahydrofurane). We attribute this to strong
      interchain interactions within densely grafted P3HT chains, which can be tuned by
      changing the surface curvature (or size) of the supporting particle. The hairy
      P3HT nanoparticles were successfully applied in bulk heterojunction solar cells.

PMID- 19860409
TI  - Hyperpolarized [2-13C]-fructose: a hemiketal DNP substrate for in vivo metabolic
      imaging.
AB  - Hyperpolarized (13)C labeled molecular probes have been used to investigate
      metabolic pathways of interest as well as facilitate in vivo spectroscopic
      imaging by taking advantage of the dramatic signal enhancement provided by DNP.
      Due to the limited lifetime of the hyperpolarized nucleus, with signal decay
      dependent on T(1) relaxation, carboxylate carbons have been the primary targets
      for development of hyperpolarized metabolic probes. The use of these carbon
      nuclei makes it difficult to investigate upstream glycolytic processes, which
      have been related to both cancer metabolism as well as other metabolic
      abnormalities, such as fatty liver disease and diabetes. Glucose carbons have
      very short T(1)s (<1 s) and therefore cannot be used as an in vivo hyperpolarized
      metabolic probe of glycolysis. However, the pentose analogue fructose can also
      enter glycolysis through its phosphorylation by hexokinase and yield
      complementary information. The C(2) of fructose is a hemiketal that has a
      relatively longer relaxation time (approximately 16 s at 37 degrees C) and high
      solution state polarization (approximately 12%). Hyperpolarized [2-(13)C]
      fructose was also injected into a transgenic model of prostate cancer (TRAMP) and
      demonstrated difference in uptake and metabolism in regions of tumor relative to
      surrounding tissue. Thus, this study demonstrates the first hyperpolarization of
      a carbohydrate carbon with a sufficient T(1) and solution state polarization for
      ex vivo spectroscopy and in vivo spectroscopic imaging studies.

PMID- 19860411
TI  - Assignment of Ile, Leu, and Val methyl correlations in supra-molecular systems:
      an application to aspartate transcarbamoylase.
AB  - A number of complementary approaches for the assignment of Ile, Leu, and Val
      methyl groups in Methyl-TROSY spectra of supra-molecular protein complexes are
      presented and compared. This includes the transfer of assignments from smaller
      fragments to the complex using a "divide-and-conquer" approach, assignment
      transfer via exchange spectroscopy, or, alternatively, generating assignments of
      the complex through the measurement of pseudocontact shifts, facilitated by the
      introduction of paramagnetic probes. The methodology is applied to the assignment
      of the regulatory chains in the 300 kDa enzyme aspartate transcarbamoylase,
      ATCase. The "divide-and-conquer" method that has proven to be very powerful in
      applications to other systems produced assignments for approximately 60% of the
      observed methyl groups in TROSY maps of ATCase. By contrast, the combination of
      all approaches led to assignments for 86% of the methyls, providing a large
      number of probes of structure and dynamics. The derived assignments were used to
      interpret chemical shift changes of ATCase upon titration with the nucleotide
      ATP. Large shift changes in the N-terminal tails of the regulatory chain provide
      the first evidence for structural perturbations in a region that is known to play
      a critical role on the effect of nucleotide binding on distal catalytic sites of
      this allosteric enzyme.

PMID- 19860412
TI  - Application of random forest approach to QSAR prediction of aquatic toxicity.
AB  - This work is devoted to the application of the random forest approach to QSAR
      analysis of aquatic toxicity of chemical compounds tested on Tetrahymena
      pyriformis. The simplex representation of the molecular structure approach
      implemented in HiT QSAR Software was used for descriptors generation on a two
      dimensional level. Adequate models based on simplex descriptors and the RF
      statistical approach were obtained on a modeling set of 644 compounds. Model
      predictivity was validated on two external test sets of 339 and 110 compounds.
      The high impact of lipophilicity and polarizability of investigated compounds on
      toxicity was determined. It was shown that RF models were tolerant for insertion
      of irrelevant descriptors as well as for randomization of some part of toxicity
      values that were representing a "noise". The fast procedure of optimization of
      the number of trees in the random forest has been proposed. The discussed RF
      model had comparable or better statistical characteristics than the corresponding
      PLS or KNN models.

PMID- 19860414
TI  - Heterogeneous ultrathin films of poly(vinyl alcohol)/layered double hydroxide and
      montmorillonite nanosheets via layer-by-layer assembly.
AB  - In this paper, Co-Al layered double hydroxide (LDH) and montmorillonite (MMT)
      have been exfoliated into charged single layers in the solvent of formamide and
      water, respectively. The structures of individual layers of LDH and MMT were
      characterized by X-ray diffraction (XRD) and atomic force microscopy (AFM). The
      delamination mechanisms of LDH and MMT were also discussed. Furthermore,
      heterogeneous ultrathin films of poly(vinyl alcohol) (PVA)/charged inorganic
      nanosheets, (PVA/MMT/PVA/LDH)(n), were fabricated by layer-by-layer (LBL)
      assembly via hydrogen bonding. The LBL assembly process was monitored by UV-vis
      spectroscopy, and the structures of the heterogeneous ultrathin films were
      analyzed by XRD.

PMID- 19860413
TI  - Structural identification of Diindole agonists of the aryl hydrocarbon receptor
      derived from degradation of indole-3-pyruvic acid.
AB  - Aerobic incubation of the tryptophan transamination/oxidation product indole-3
      pyruvic acid (I3P) at pH 7.4 and 37 degrees C yielded products with activity as
      Ah receptor (AHR) agonists. The extracts were fractionated using HPLC and
      screened for AHR agonist activity. Two compounds were identified as agonists: 1,3
      di(1H-indol-3-yl)propan-2-one (1) and 1-(1H-indol-3-yl)-3-(3H-indol-3-ylidene)
      propan-2-one (2), with the potency of 2 being 100-fold > 1 [ Nguyen et al. ( 2009
      ) Chem. Res. Toxicol. , DOI: 10.1021/tx900043s . ]. Both 1 and 2 showed UV
      spectra indicative of indole. The molecular formulas were established by high
      resolution mass spectrometry (HRMS), and the structures were determined by a
      combination of NMR methods, including (1)H, natural abundance (13)C, and two
      dimensional methods. An intermediate in the oxidation of I3P to 1 is 3-hydroxy
      2,4-di(1H-indol-3-yl)butanal (HRMS established the presence of a compound with
      the formula C(20)H(19)N(2)O(2)). Compound 1 was converted to 2 in air or (faster)
      with mild oxidants, and 2 could be further oxidized to 1,3-di(3H-indol-3
      ylidene)propan-2-one. Determination of the structures allowed estimation of the
      molar Ah receptor agonist activity of these natural products, similar in potency
      to known classical AHR inducers.

PMID- 19860416
TI  - Oligocarbonate molecular transporters: oligomerization-based syntheses and cell
      penetrating studies.
AB  - A new family of guanidinium-rich molecular transporters featuring a novel
      oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can
      be rapidly assembled irrespective of length in a one-step oligomerization
      strategy that can proceed with concomitant introduction of probes (or by analogy
      drugs). The new transporters exhibit excellent cellular entry as determined by
      flow cytometry and fluorescence microscopy, and the functionality of their drug
      delivery capabilities was confirmed by the delivery of the bioluminescent small
      molecule probe luciferin and turnover by its intracellular target enzyme.

PMID- 19860415
TI  - D-amino acid oxidase generates agonists of the aryl hydrocarbon receptor from D
      tryptophan.
AB  - The aryl hydrocarbon receptor (AHR) is well-known for its role in mediating the
      toxic and adaptive responses to xenobiotic compounds. Recent studies also
      indicate that AHR ligands are endogenously produced and may be essential for
      normal development. Previously, we showed that the endogenous enzyme, aspartate
      aminotransferase (AST), generates the AHR proagonist, indole-3-pyruvic acid
      (I3P), by deamination of its substrate L-tryptophan. We hypothesized that other
      enzymatic pathways capable of producing I3P may generate AHR agonists in vivo. We
      now demonstrate that the enzyme d-amino acid oxidase (DAAO) catalyzes the
      production of AHR agonists through the enzymatic conversion of D-tryptophan to
      I3P. Moreover, we provide evidence that the nonenzymatic oxidation and
      condensation of I3P is a critical step in the generation of receptor agonists by
      DAAO and AST. Products of this process include two novel agonists, 1,3-di(1H
      indol-3-yl)propan-2-one and 1-(1H-indol-3-yl)-3-(3H-indol-3-ylidene) propan-2-one
      [characterized in the accompanying paper, Chowdhury et al. ( 2009 ) Chem. Res.
      Toxicol. , DOI: 10.1021/tx9000418 ], both of which can potently activate the AHR
      at concentrations in the nanomolar range. These results show that endogenous AHR
      activity can be modulated by I3P production from amino acid precursors through
      multiple enzymatic pathways, including those catalyzed by DAAO and AST.

PMID- 19860417
TI  - Direct evidence for the interfacial oxidation of CO with hydroxyls catalyzed by
      Pt/oxide nanocatalysts.
AB  - By rational design of the FeO(111)/Pt(111) inverse model catalyst and the control
      experiments, we report for the first time direct experimental evidence for the
      interfacial CO(ads) + OH(ads) reaction to produce CO(2) at the Pt-oxide interface
      at low temperatures, providing deep insights into the reaction mechanism and
      active site of the important low-temperature water-gas shift and preferential CO
      oxidation reactions catalyzed by Pt/oxide nanocatalysts at the molecular level.

PMID- 19860418
TI  - Proteome changes during meat aging in tough and tender beef suggest the
      importance of apoptosis and protein solubility for beef aging and tenderization.
AB  - Within a population of Charolais young bulls, two extreme groups of longissimus
      thoracis muscle samples, classified according to Warner-Bratzler shear force
      (WBSF) of 55 degrees C grilled meat, were analyzed by 2D-electrophoresis. Muscle
      analyses were performed on 4 bulls of the "tender" group (WBSF=27.7+/-4.8 N) and
      4 bulls of the "tough" group (WBSF=41.2+/-6.1 N), at 3 post-mortem times: D0,
      samples taken within 10 min post-mortem; D5 and D21, samples kept at 4 degrees C
      under vacuum during 5 and 21 days. Proteins of muscle samples were separated in
      two fractions based on protein solubility in Tris buffer: "soluble" and
      "insoluble". Proteins of both fractions were separated by 2D-electrophoresis.
      Evolution of spots during the 3 post-mortem times was analyzed by hierarchical
      classification (HCA). Three clusters of proteins presenting similar evolution
      profiles provided accurate classification of post-mortem times and showed the
      translocation of some chaperone proteins and glycolytic enzymes from the soluble
      fraction to the insoluble fraction between D0 and D5. Cellular structure
      dismantlement and proteolysis was observed at D21. Effect of group ("tender" vs
      "tough") on spot intensities was tested by ANOVA. At D0, higher quantity of
      proteins of the inner and outer membrane of mitochondria was found in the tender
      group suggesting a more extensive degradation of mitochondria that may be related
      to the apoptotic process.

PMID- 19860419
TI  - Negative evidence for stachydrine or Galeopsis ladanum L. seeds as the causal
      agents of coturnism after quail meat ingestion.
AB  - Quail poisoning is known to produce an acute myoglobinuric syndrome called
      coturnism. The cause of this syndrome is still unknown, although it has been
      postulated that Galeopsis ladanum L. seeds, in particular lipidic compounds or
      stachydrine, are responsible for this toxicity. Thus, we aimed to study the
      implication of this plant in coturnism in order to explore the physiopathology of
      the disease, especially with regard to stachydrine and lipidic compounds
      extracted from seeds. For this purpose, Wistar rats were fed with G. ladanum seed
      extracts or with quail meat. However, the rhabdomyolysis outbreak could not be
      reproduced in any case. Therefore, in view of our results and experimental
      conditions, seeds of G. ladanum and stachydrine do not appear to be the
      responsible agents of the myopathic outbreak. This conclusion is supported by the
      following facts: direct administration of extracts of seeds of G. ladanum or
      stachydrine produces no myotoxicity in rats; G. ladanum seeds are not toxic to
      quails and meat from quails fed G. ladanum seeds is not toxic to rats.

PMID- 19860420
TI  - Evidence of significant covalent bonding in Au(CN)(2)(-).
AB  - The Au(CN)(2)(-) ion is the most stable Au compound known for centuries, yet a
      detailed understanding of its chemical bonding is still lacking. Here we report
      direct experimental evidence of significant covalent bonding character in the Au
      C bonds in Au(CN)(2)(-) using photoelectron spectroscopy and comparisons with its
      lighter congeners, Ag(CN)(2)(-) and Cu(CN)(2)(-). Vibrational progressions in the
      Au-C stretching mode were observed for all detachment transitions for Au(CN)(2)(
      ), in contrast to the atomic-like transitions for Cu(CN)(2)(-), revealing the Au
      C covalent bonding character. In addition, rich electronic structural information
      was obtained for Au(CN)(2)(-) by employing 118 nm detachment photons. Density
      functional theory and high-level ab initio calculations were carried out to
      understand the photoelectron spectra and obtain insight into the nature of the
      chemical bonding in the M(CN)(2)(-) complexes. Significant covalent character in
      the Au-C bonding due to the strong relativistic effects was revealed in
      Au(CN)(2)(-), consistent with its high stability.

PMID- 19860421
TI  - Isolating surface-enhanced Raman scattering hot spots using multiphoton
      lithography.
AB  - We present a method for improving femtomole-level trace detection (10(9)
      molecules) using large-area surface-enhanced Raman scattering (SERS) substrates.
      Using multiphoton-induced exposure of a commercial photoresist, we physically
      limit the available molecular adsorption sites to only the electromagnetic "hot
      spots" on the substrate. This process prevents molecules from adsorbing to sites
      of weak SERS enhancement, while permitting adsorption to sites of extraordinary
      SERS enhancement. For a randomly adsorbed submonolayer of benzenethiol molecules
      the average Raman scattering cross section of the processed sample is 27 times
      larger than that of an unprocessed SERS substrate.

PMID- 19860422
TI  - Carboxyl-catalyzed prototropic rearrangements in histidine peptide radicals upon
      electron transfer: effects of peptide sequence and conformation.
AB  - We report an unusual prototropic rearrangement in gas-phase radicals formed by
      collisional electron transfer from cesium atoms to protonated peptides HAL, AHL,
      and ALH at 50 keV. The rearrangement depends on the peptide amino acid sequence
      and presence or steric accessibility of a free carboxyl group. Upon electron
      transfer, protonated HAL and ALH rearrange to tautomers that are detected as
      nondissociated anions in charge-reversal mass spectra. The isomerization is minor
      in protonated ALH and virtually absent in HAL amide. Electron structure
      calculations indicate that the gas-phase ions are preferentially protonated in
      the His imidazole ring and consist of multiple conformers that differ in their
      hydrogen bonding patterns. Electron transfer to protonated HAL and AHL triggers
      an exothermic and dynamically barrierless transfer of the carboxyl proton onto
      the C-2' position of the His ring that occurs on a 120-240 ns time scale. The
      kinetics of this isomerization are controlled by internal rotations in the
      radicals to assume conformations favoring the proton transfer. The radical
      conformations also affect subsequent proton migrations in zwitterionic His
      imidazoline intermediates that reform the COOH group and result in His ring
      isomerization. This autocatalytic prototropic rearrangement in gas-phase peptide
      radicals is analogous to enzyme catalytic reactions involving His and acidic
      amino acid residues. In contrast to HAL and AHL, the C-2' position is sterically
      inaccessible in ALH radicals. These radicals undergo proton migrations to the His
      ring C-5' positions that have moderate energy barriers and are less efficient.
      RRKM calculations on the combined B3LYP and PMP2/6-311++G(2d,p) potential energy
      surface of the ground doublet electronic state of the peptide radicals provided
      rate constants that were quantitatively consistent with the dissociations
      observed in the gas phase. The formation of minor sequence z(1) and z(2)
      fragments from AHL was interpreted as occurring in the first excited state of the
      radical.

PMID- 19860424
TI  - Highlights in the discovery of antiviral drugs: a personal retrospective.

PMID- 19860426
TI  - Total synthesis and absolute stereochemistry of integric acid.
AB  - An efficient total synthesis of integric acid is described starting from the
      Wieland-Miescher ketone. Key steps involve a one-step orthogonal
      deprotection/protection strategy of a thioacetal/aldehyde and the selective
      oxidative cleavage of a prenyl group in the presence of two other unsaturated
      moieties. The synthesis of both C4' diastereoisomers of integric acid delivered
      unambiguous evidence for (S)-stereochemistry at the C4' position.

PMID- 19860425
TI  - Copper-mediated amidation of heterocyclic and aromatic C-H bonds.
AB  - A copper-mediated aerobic coupling reaction enables direct amidation of
      heterocycles or aromatics having weakly acidic C-H bonds with a variety of
      nitrogen nucleophiles. These reactions provide efficient access to many
      biologically important skeletons, including ones with the potential to serve as
      inhibitors of HMTs.

PMID- 19860427
TI  - New strategies for the design of folded peptoids revealed by a survey of
      noncovalent interactions in model systems.
AB  - Controlling the equilibria between backbone cis- and trans-amides in peptoids, or
      N-substituted glycine oligomers, constitutes a significant challenge in the
      construction of discretely folded peptoid structures. Through the analysis of a
      set of monomeric peptoid model systems, we have developed new and general
      strategies for controlling peptoid conformation that utilize local noncovalent
      interactions to regulate backbone amide rotameric equilibria, including n-->pi*,
      steric, and hydrogen bonding interactions. The chemical functionalities required
      to implement these strategies are typically confined to the peptoid side chains,
      preserve chirality at the side chain N-alpha-carbon known to engender peptoid
      structure, and are fully compatible with standard peptoid synthesis techniques.
      Our examinations of peptoid model systems have also elucidated how solvents
      affect various side chain-backbone interactions, revealing fundamental aspects of
      these noncovalent interactions in peptoids that were largely uncharacterized
      previously. As validation of our monomeric model systems, we extended the scope
      of this study to include peptoid oligomers and have now demonstrated the
      importance of local steric and n-->pi* interactions in dictating the structures
      of larger, folded peptoids. This new, modular design strategy has guided the
      construction of peptoids containing 1-naphthylethyl side chains, which we show
      can be utilized to effectively eliminate trans-amide rotamers from the peptoid
      backbone, yielding the most conformationally homogeneous class of peptoid
      structures yet reported in terms of amide rotamerism. Overall, this research has
      afforded a valuable and expansive set of design tools for the construction of
      both discretely folded peptoids and structurally biased peptoid libraries and
      should shape our understanding of peptoid folding.

PMID- 19860428
TI  - Inverse-fluorescence correlation spectroscopy.
AB  - An alternative version of fluorescence correlation spectroscopy is presented,
      where the signal from a medium surrounding the particles of interest is analyzed,
      as opposed to a signal from the particles themselves. This allows for analysis of
      unlabeled particles and potentially of biomolecules. Here, the concept together
      with principal experiments on polystyrene beads of 100, 200, 400, and 800 nm
      diameter in an aqueous solution of alexa 488-fluorophores are presented. The use
      of photo detectors allowing higher photon fluxes, or of reduced detection
      volumes, should enable analysis of significantly smaller particles or even
      biomolecules.

PMID- 19860429
TI  - Physico-chemical characterization of polylipid nanoparticles for gene delivery to
      the liver.
AB  - Polylipid nanoparticles (PLNP) have been shown to be very effective in delivering
      antioxidative genes in the treatment of liver injury in mice. To build on our
      previous studies and to further characterize PLNP formulated from polycationic
      lipid (PCL) and cholesterol, we report here the synthesis of multigram quantities
      of PCL and employ analytical tools, such as Raman spectroscopy of single PLNP and
      live-cell imaging of lipofection, for the physicochemical characterization of
      PCL, PLNP, and the transfection process. Mass spectrometry demonstrates the
      characteristics of polymeric lipids. Raman spectrum of PCL reveals the polymeric
      structure of the polymers. The presence of cholesterol in PLNP formulation did
      not markedly change the Raman spectrum. PLNP-derived polyplexes exhibit Raman
      spectra very similar to PLNP except that the C-H out-of-plane deformation mode of
      the polymeric lipid is significantly suppressed, indicating the interaction with
      plasmid DNA. Zeta potential measurement indicates a large DNA-carrying capacity
      of PLNP and their stability for in vivo gene delivery. The live-cell fluorescent
      imaging dynamically shows that PLNP exerts transfection efficiency similar to
      lipofectamine in leading to early reporter gene expression in live hepatic cells.
      In conclusion, polylipid nanoparticles possess a high DNA carrying capacity and
      lipofection efficiency, rendering them suitable for testing in large animals. The
      employment of novel state-of-the-art technologies in the study of lipofection
      represents the level of physicochemical and biological characterization that is
      needed to best understand the key elements involved in the lipofection process.

PMID- 19860430
TI  - Metabolism of procymidone derivatives in female rats.
AB  - PCM-CH2OH [N-(3,5-dichlorophenyl)-1-hydroxymethyl-2-methylcyclopropane-1,2
      dicarboximide] and PA-CH2OH [2-carboxyl-N-(3,5-dichlorophenyl)-1-hydroxymethyl-2
      methylcyclopropane-1-carboxamide] are metabolites of the fungicide procymidone [N
      (3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide] in rat. The
      distribution and metabolism of PCM-CH2OH and PA-CH2OH were here clarified by
      analyzing plasma and tissues (liver, kidney, heart, lung, spleen and ovary) of
      female rats after single subcutaneous administration of [phenyl-14C]PCM-CH2OH and
      [phenyl-14C]PA-CH2OH at 62.5 mg/kg, respectively. In both rats dosed with PCM
      CH2OH and PA-CH2OH, the radioactivity was similarly distributed into plasma and
      tissues, and PA-CH2OH was detected as the main metabolite in plasma, whereas PCM
      CH2OH predominated in tissues except for kidney at 1 h after administration of PA
      CH2OH. Furthermore, the cyclization ratio [PCM-CH2OH/(PCM-CH2OH+PA-CH2OH)]
      increased in tissues of PA-CH2OH dosed rats with passage of time. Both
      procymidone and PCM-CH2OH have convertible conformations (closed and open ring
      forms), so influence of pH conditions to their conversion was examined. Both
      compounds demonstrated closed rings under acidic conditions, and open rings under
      alkaline conditions. Generally, intracellar pH is kept at approximately neutral,
      and extracellular pH is kept at 0.6-0.7 units higher in all the animal species,
      so that our in vitro results supported in vivo findings.

PMID- 19860431
TI  - chi-Conopeptide pharmacophore development: toward a novel class of norepinephrine
      transporter inhibitor (Xen2174) for pain.
AB  - Norepinephrine (NE) amplifies the strength of descending pain inhibition, giving
      inhibitors of spinal NET clinical utility in the management of pain. chi-MrIA
      isolated from the venom of a predatory marine snail noncompetitively inhibits NET
      and reverses allodynia in rat models of neuropathic pain. An analogue of chi-MrIA
      has been found to be a suitable drug candidate. On the basis of the NMR solution
      structure of this related peptide, Xen2174 (3), and structure-activity
      relationships of analogues, a pharmacophore model for the allosteric binding of 3
      to NET is proposed. It is shown that 3 interacts with NET predominantly through
      amino acids in the first loop, forming a tight inverse turn presenting amino
      acids Tyr7, Lys8, and Leu9 in an orientation allowing for high affinity
      interaction with NET. The second loop interacts with a large hydrophobic pocket
      within the transporter. Analogues based on the pharmacophore demonstrated
      activities that support the proposed model. On the basis of improved chemical
      stability and a wide therapeutic index, 3 was selected for further development
      and is currently in phase II clinical trials.

PMID- 19860432
TI  - alphavbeta3 Integrin-targeting Arg-Gly-Asp (RGD) peptidomimetics containing
      oligoethylene glycol (OEG) spacers.
AB  - RGD peptides are used in biomaterials science for surface modifications with a
      view to elicit selective cellular responses. Our objective is to replace peptides
      by small peptidomimetics acting similarly. We designed novel molecules targeting
      alpha(v)beta(3) integrin and featuring spacer-arms (for surface grafting), which
      do not disturb the biological activity, from (l) N-(3
      (trifluoromethyl)benzenesulfonyl) tyrosine used as scaffold. Various Arg-mimics
      were fixed on the phenol function, and the ortho position was used for the
      coupling of OEG spacers. All peptidomimetics were active in the nM range in a
      binding test toward human alpha(v)beta(3) integrin (IC(50) = 0.1 to 1.7 nM) and
      selective versus platelet integrin alpha(IIb)beta(3). Selected compounds revealed
      excellent ability to inhibit bone cells adhesion on vitronectin. Modeling and
      docking studies were performed for comparing the most active RGD peptidomimetic
      to cilengitide, i.e., cyclo-[RGDfN(Me)V]-. Lastly, the adhesion of endothelial
      cells on a cultivation support grafted with RGD peptidomimetics was significantly
      improved.

PMID- 19860433
TI  - Synthesis, crystallization, and biological evaluation of an orally active prodrug
      of gemcitabine.
AB  - The design, synthesis, and biological characterization of an orally active
      prodrug (3) of gemcitabine are described. Additionally, the identification of a
      novel co-crystal solid form of the compound is presented. Valproate amide 3 is
      orally bioavailable and releases gemcitabine into the systemic circulation after
      passing through the intestinal mucosa. The compound has entered clinical trials
      and is being evaluated as a potential new anticancer agent.

PMID- 19860434
TI  - A novel manganese complex effective as superoxide anion scavenger and therapeutic
      agent against cell and tissue oxidative injury.
AB  - Two cyclic polyamine-polycarboxylate ligands, 1,4,7,10-tetraazacyclododecane-1,7
      diacetic acid (H(2)L3) and 4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7
      diacetic acid (H(2)L4), and two noncyclic scaffolds, N-(2
      hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid (H(3)L1) and ethylene
      bisglycol-tetracetic acid (H(4)L2), form stable complexes with Mn(II) in aqueous
      solutions. Cyclic voltammograms show that the complexes with the most hydrophobic
      ligands, [MnL2](2-) and [MnL4], are oxidized at higher potential than [MnL1](-)
      and [MnL3]. The pharmacological properties of these molecules were evaluated as
      superoxide ion scavengers and anti-inflammatory compounds. Among the four
      complexes, [MnL4] was the most bioactive, being effective in the
      nanomolar/micromolar range. It abates the levels of key markers of oxidative
      injury on cultured cells and ameliorates the outcome parameters in animal models
      of acute and chronic inflammation. [MnL4] toxicity was very low on both cell
      cultures in vitro and mice in vivo. Hence, we propose [MnL4] as a novel stable
      oxygen radical scavenging molecule, active at low doses and with a low toxicity.

PMID- 19860435
TI  - Role of water in the multifaceted catalytic antibody 4B2 for allylic
      isomerization and Kemp elimination reactions.
AB  - Specificity toward a single reaction is a well-known characteristic of catalytic
      antibodies. However, contrary to convention, catalytic antibody 4B2 possesses the
      ability to efficiently catalyze two unrelated reactions: a Kemp elimination and
      an allylic isomerization of a beta,gamma-unsaturated ketone. To elucidate how
      this multifaceted antibody operates, mixed quantum and molecular mechanics
      calculations coupled to Monte Carlo simulations were carried out. The antibody
      was determined to derive its adaptability for the mechanistically different
      reactions through the rearrangement of water molecules in the active site into
      advantageous geometric orientations for enhanced electrostatic stabilization. In
      the case of the Kemp elimination, a general base, Glu L34, carried out the proton
      abstraction from the isoxazole ring of 5-nitro-benzisoxazole while water
      molecules delivered specific stabilization at the transition state. The role of
      water was found to be more pronounced in the allylic isomerization because the
      solvent actively participated in the stepwise mechanism. A rate-limiting
      abstraction of the alpha-proton from the beta,gamma-unsaturated ketone via Glu
      L34 led to the formation of a neutral dienol intermediate, which was rapidly
      reprotonated at the gamma-position via a solvent hydronium ion. Preferential
      channeling of H(3)O(+) in the active site ensured a stereoselective proton
      exchange from the alpha- to the gamma-position, in good agreement with deuterium
      exchange NMR and HPLC experiments. Ideas for improved water-mediated catalytic
      antibody designs are presented. In a technical advancement, improvements to a
      recent polynomial fitting and integration technique utilizing free energy
      perturbation theory delivered greater accuracy and speed gains.

PMID- 19860436
TI  - Analysis of 23 polycyclic aromatic hydrocarbons in smokeless tobacco by gas
      chromatography-mass spectrometry.
AB  - Smokeless tobacco contains 28 known carcinogens and causes precancerous oral
      lesions and oral and pancreatic cancer. A recent study conducted by our research
      team identified eight different polycyclic aromatic hydrocarbons (PAHs) in U.S.
      moist snuff, encouraging further investigations of this group of toxicants and
      carcinogens in smokeless tobacco products. In this study, we developed a gas
      chromatography-mass spectrometry method that allows simultaneous analysis of 23
      various PAHs in smokeless tobacco after a simple two-step extraction and
      purification procedure. The method produced coefficients of variation under 10%
      for most PAHs. The limits of quantitation for different PAHs varied between 0.3
      and 11 ng/g tobacco, starting with a 300 mg sample. The recovery of the stable
      isotope-labeled internal standards averaged 87%. The method was applied to
      analysis of 23 moist snuff samples that included various flavors of the most
      popular U.S. moist snuff brands, as well as 17 samples representing the currently
      marketed brands of spit-free tobacco pouches, a relatively new type of smokeless
      tobacco. The sum of all detected PAHs in conventional moist snuff averaged 11.6
      (+/-3.7) microg/g dry weight; 20% of this amount was comprised of carcinogenic
      PAHs. The levels of PAHs in new spit-free tobacco products were much lower than
      those in moist snuff; the sum of all detected PAHs averaged 1.3 (+/-0.28)
      microg/g dry weight. Our findings render PAHs one of the most prevalent groups of
      carcinogens in smokeless tobacco. Urgent measures are required from the U.S.
      tobacco industry to modify manufacturing processes so that the levels of these
      toxicants and carcinogens in U.S. moist snuff are greatly reduced.

PMID- 19860437
TI  - Physicochemical and conformational properties of buckwheat protein isolates:
      influence of polyphenol removal with cold organic solvents from buckwheat seed
      flours.
AB  - The effects of polyphenol removal from common buckwheat seed flours with cold
      aqueous organic solvents (including 95% ethanol, 70% 2-propanol, and 80%
      methanol, v/v) on the physicochemical and conformational properties of their
      protein isolates (BPI) were investigated. The extraction resulted in considerable
      reduction in its polyphenol content, especially protein-bound polyphenol content,
      and concomitant increase in its protein content. The efficiency of the removal of
      the polyphenols was much better in the 2-propanol case than in other two cases.
      The surface hydrophobicity of the proteins changed slightly, while the disulfide
      bond contents remarkably increased, partially at the expense of free sulfhydryl
      group contents. The protein solubility in the pH range of 7.0-11.0 and the
      proportion of undenatured globulins in BPI products were variably improved by the
      organic solvent extraction, and the extent of the improvements was highest in the
      2-propanol case. Intrinsic emission fluorescence and far-UV and/or near-UV CD
      spectra showed that polyphenol removal resulted in significant changes in
      tertiary and/or secondary conformations of the proteins in BPI, and the changes
      were also related to the efficiency of the removal of the polyphenols. These
      results suggest that the physicochemical and conformational properties of BPI are
      closely related to its polyphenol level, and there is also a close relationship
      between its physicochemical properties and tertiary and/or secondary
      conformations.

PMID- 19860438
TI  - Orientational landscapes of peptides in membranes: prediction of (2)H NMR
      couplings in a dynamic context.
AB  - Unlike soluble proteins, membrane polypeptides face an anisotropic milieu. This
      imposes restraints on their orientation and provides a reference that makes
      structure prediction tractable by minimalistic thermodynamic models. Here we use
      this framework to build orientational distributions of monomeric membrane-bound
      peptides and to predict their expected solid-state (2)H NMR quadrupolar couplings
      when labeled at specific side chain positions. Using a complete rigid-body
      sampling of configurations relative to an implicit lipid membrane, peptide free
      energy landscapes are calculated. This allows us to obtain probability
      distributions of the peptide tilt, azimuthal rotation, and depth of membrane
      insertion. The orientational distributions are broad and originate from an
      interplay among the three relevant rigid-body degrees of freedom, which allows
      population of multiple states in shallow free energy minima. Remarkably, only
      when the orientational distributions are taken into account do we obtain a close
      correlation between predicted (2)H NMR splittings and values measured in
      experiments. Such a good correlation is not seen with splittings calculated from
      single configurations, being either the averaged or the lowest free energy state,
      showing there are distributions, rather than single structures, that best define
      the peptide-membrane systems. Moreover, we propose that these distributions
      contribute to the understanding of the rigid-body dynamics of the system.

PMID- 19860439
TI  - Transport properties of tetrahedral, network-forming ionic melts.
AB  - Molecular dynamics simulations of liquid silica and beryllium fluoride are
      performed using the van Beest-Kramer-van Santen and transferable rigid ion model
      potentials, respectively, in order to compare transport properties. The ionic
      conductivity (sigma), shear viscosity (eta) and ionic self-diffusivities (D(+/-))
      are computed over a fairly wide range of temperatures and densities and
      deviations from Arrhenius behavior along different isochores is studied. The
      Stokes-Einstein relation is shown to hold over the entire range of state points,
      though the effective hydrodynamic radius shows small variations due to thermal
      fluctuations, compression, and local tetrahedral order. Several alternative tests
      of the Nernst-Einstein relation are implemented which show that significant
      network-formation in the anomalous regime leads to a breakdown of this
      relationship. The relaxation times, tau(sigma) and tau(M), associated with the
      decay of the charge-flux and pressure ACFs respectively, are computed. In the
      anomalous regime, as the tetrahedral network formation progresses, tau(M)
      increases rapidly while tau(sigma) shows very little variation, indicating a
      decoupling of charge and momentum transport processes.

PMID- 19860441
TI  - Deuteration impact on micellization pressure and cloud pressure of polystyrene
      block-polybutadiene and polystyrene-block-polyisoprene in compressible propane.
AB  - The deuterated homopolymers and their corresponding polystyrene-block
      polybutadiene and polystyrene-block-polyisoprene copolymers require lower cloud
      pressures than their hydrogenous analogues to dissolve in a compressible alkane
      solvent, such as propane. For symmetric diblocks, deuteration reduces the
      micellization pressure. By contrast, for asymmetric diblocks with a long diene
      block relative to the styrene block, deuteration can increase the micellization
      pressure. All in all, however, the deuteration effects, while measurable, do not
      qualitatively change the principal diblock properties in compressible propane
      solutions, such as pressure-induced micelle decomposition, micelle formation and
      micelle size, and their temperature dependence. Therefore, isotope labeling
      should be a useful approach to neutron-scattering characterization for styrene
      diene block copolymers in compressible alkane systems.

PMID- 19860440
TI  - Dynamics of activation of lecithin:cholesterol acyltransferase by apolipoprotein
      A-I.
AB  - The product of transesterification of phospholipid acyl chains and unesterified
      cholesterol (UC) by the enzyme lecithin:cholesterol acyltransferase (LCAT) is
      cholesteryl ester (CE). Activation of LCAT by apolipoprotein (apo) A-I on nascent
      (discoidal) high-density lipoproteins (HDL) is essential for formation of mature
      (spheroidal) HDL during the antiatherogenic process of reverse cholesterol
      transport. Here we report all-atom and coarse-grained (CG) molecular dynamics
      (MD) simulations of HDL particles that have major implications for mechanisms of
      LCAT activation. Both the all-atom and CG simulations provide support for a model
      in which the helix 5/5 domains of apoA-I create an amphipathic "presentation
      tunnel" that exposes methyl ends of acyl chains at the bilayer center to solvent.
      Further, CG simulations show that UC also becomes inserted with high efficiency
      into the amphipathic presentation tunnel with its hydroxyl moiety (UC-OH) exposed
      to solvent; these results are consistent with trajectory analyses of the all-atom
      simulations showing that UC is being concentrated in the vicinity of the
      presentation tunnel. Finally, consistent with known product inhibition of CE-rich
      HDL by CE, CG simulations of CE-rich spheroidal HDL indicate partial blockage of
      the amphipathic presentation tunnel by CE. These results lead us to propose the
      following working hypothesis. After attachment of LCAT to discoidal HDL, the
      helix 5/5 domains in apoA-I form amphipathic presentation tunnels for migration
      of hydrophobic acyl chains and amphipathic UC from the bilayer to the
      phospholipase A2-like and esterification active sites of LCAT, respectively. This
      hypothesis is currently being tested by site-directed mutagenesis.

PMID- 19860442
TI  - Inhibiting lateral domain formation in lipid bilayers: simulations of alternative
      steroid headgroup chemistries.
AB  - Cholesterol is an essential component of lateral domain formation in lipid
      bilayers. Experiments using structural analogues of cholesterol have revealed
      that slight changes to the steroid headgroup chemistry can lead to significantly
      different degrees of domain formation. For example, the seemingly slight
      modification to 4-cholesten-3beta-one changes the molecule from domain enhancing
      to domain inhibiting. To investigate the relationship between steroid headgroup
      structure and domain formation, we have performed a series of coarse-grain
      molecular dynamics simulations in which the hydrophobicity of the steroid
      headgroup is altered. We show that bilayers containing steroids with polar
      headgroups undergo lateral phase separation, with the steroids adopting the
      canonical, upright orientation. However, increasing the hydrophobicity of the
      steroid's headgroup dramatically changes the orientation of the molecule such
      that it lies at the center of the bilayer, perpendicular to the bilayer normal.
      As a fundamental consequence, we show that these steroids inhibit the formation
      of phase-separated domains in membranes.

PMID- 19860444
TI  - Multiply enhanced odd-order wave-mixing spectroscopy.
AB  - Extending current coherent multidimensional spectroscopy (CMDS) methods to higher
      order multiwave mixing requires excitation intensities where dynamic Stark
      effects become important. This paper examines the dynamic Stark effects that
      occur in mixed frequency/time domain CMDS methods at high excitation intensities
      in a model system with an isolated vibrational state. The phase-matching
      restrictions in CMDS define the excitation beams that interact by nonlinear
      mixing while the dynamic Stark effects create vibrational ladders of increasingly
      more energetic overtone and combination band states. The excited quantum states
      form coherences that reemit the output beams. This paper uses the phase-matching
      conditions k(out) = k(1) - k(2) + k(2') and k(out) =- k(1) + k(2) + k(2'), where
      the subscripts denote the excitation frequencies of each excitation pulse and the
      output pulse. The phase-matching condition constrains each pulse to have an odd
      number of interactions so the overall mixing process that creates the output
      coherence must also involve an odd number of interactions. Tuning the excitation
      frequencies and spectrally resolving the output intensity creates three
      dimensional spectra that resolve the individual overtone states. Changing the
      excitation pulse time delays measures the dynamics of the coherences and
      populations created by the multiple excitations. The multidimensional spectra
      probe the highly excited states of a molecular potential energy surface. This
      paper uses tungsten hexacarbonyl (W(CO)(6)) as a model for observing how dynamic
      Stark effects change the multidimensional spectra of a simple system. The
      simplicity of the W(CO)(6) system provides the experimental data required to
      develop the nonperturbative theoretical methods that will be necessary to model
      this new approach to CMDS.

PMID- 19860443
TI  - Azido push-pull fluorogens photoactivate to produce bright fluorescent labels.
AB  - Dark azido push-pull chromophores have the ability to be photoactivated to
      produce bright fluorescent labels suitable for single-molecule imaging. Upon
      illumination, the aryl azide functionality in the fluorogens participates in a
      photochemical conversion to an aryl amine, thus restoring charge-transfer
      absorption and fluorescence. Previously, we reported that one compound, DCDHF-V-P
      azide, was photoactivatable. Here, we demonstrate that the azide-to-amine
      photoactivation process is generally applicable to a variety of push-pull
      chromophores, and we characterize the photophysical parameters including
      photoconversion quantum yield, photostability, and turn-on ratio. Azido push-pull
      fluorogens provide a new class of photoactivatable single-molecule probes for
      fluorescent labeling and super-resolution microscopy. Lastly, we demonstrate that
      photoactivated push-pull dyes can insert into bonds of nearby biomolecules,
      simultaneously forming a covalent bond and becoming fluorescent (fluorogenic
      photoaffinity labeling).

PMID- 19860445
TI  - The molecular shape of poly(propylenimine) dendrimer amphiphiles has a profound
      effect on their self assembly.
AB  - The shape of dendrimer amphiphiles has an unexpected effect on their self
      assembly. A series of diaminobutane poly(propylenimine) generation 3 dendrimer
      (DAB-dendr-(NH(2))(16)) amphiphiles has been synthesized, bearing an average of
      five (PD5), three (PD3) and one (PD1) palmitoyl group(s) per dendrimer molecule.
      Additionally DAB-dendr-(NH(2))(16) was derivatized with a layer of poly(ethylene
      glycol) (PEG, degree of polymerization = 12) groups and conjugated to an average
      of 1 palmitoyl group at the PEG end (PPD1). A final amphiphile resulted from the
      conjugation of DAB-dendr-(NH(2))(16) with 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-succinimidylpropionate (DSPE-PEG(3400)-SPA), i.e.: DPD5 (with
      4 DSPE-PEG arms). The critical micellar concentration in aqueous media followed
      the trend: DPD5 < PD5 = PD3 < PD1 < PPD1 and amphiphiles eventually formed 10-20
      nm monomolecular or multimolecular micelles and/or 200 nm spheres or tubules.
      Aggregation was entropy driven, as expected, for DPD5, PD5 and PD1 and enthalpy
      driven with the most hydrophilic compound PPD1, but was unexpectedly enthalpy
      driven for PD3. PD3 aggregates formed low capacity hydrophobic domains with a
      limited capacity for encapsulation of cyclosporine A; encapsulation levels (mole
      drug per mole polymer) were 0.099, 0.014, 0.099, and 0.735 for PD1, PD3, PD5, and
      DPD5 and, respectively. We conclude that star shaped amphiphiles such as PD3 are
      sterically hindered from self-assembling into high capacity hydrophobic domains
      in aqueous media. Amphiphile-membrane interactions were promoted by hydrophobic
      groups, but diminished by PEG moieties. DPD5 is the most suitable amphiphile for
      biomedical applications.

PMID- 19860446
TI  - Synthesis of fructooligosaccharides in banana 'prata' and its relation to
      invertase activity and sucrose accumulation.
AB  - Levels of sucrose and total fructooligosaccharides (FOS) were quantified in
      different phases of banana 'Prata' ripening during storage at ambient
      (approximately 19 degrees C) and low (approximately 10 degrees C) temperature.
      Total FOS levels were detected in the first days after harvest, whereas 1-kestose
      remained undetectable until the sucrose levels reached approximately 200 mg/g
      (dry weight) in both groups. Sucrose levels increased slowly but constantly at
      low temperature, but they elevated rapidly when the temperature was raised to 19
      degrees C. Total FOS and sucrose levels were higher in bananas stored at low
      temperature than in the control group. In both samples, total FOS levels were
      higher than those of 1-kestose. The carbohydrate profiles obtained by HPLC and
      TLC suggest the presence of neokestose, 6-kestose, and bifurcose. The enzymes
      putatively involved in banana fructosyltransferase activity were also evaluated.
      Results obtained indicate that the banana enzyme responsible for the synthesis of
      FOS by transfructosylation is an invertase rather than a sucrose-sucrosyl
      transferase-like enzyme.

PMID- 19860447
TI  - Platinum(II)-catalyzed intermolecular [3 + 2] cycloaddition of propadienyl silyl
      ethers and alkenyl ethers.
AB  - A Pt(II)-catalyzed [3 + 2] cycloaddition reaction of silyl propadienyl ethers and
      alkenyl ethers has been developed as the first example of the utilization of
      allenes as a three-carbon unit in a transition-metal-catalyzed intermolecular
      cycloaddition reaction. Pt(II)-containing 1,3-dipole equivalents generated by
      electrophilic activation of silyl propadienyl ethers using a Pt(II) catalyst
      reacted with various electron-rich alkenes to give synthetically useful
      functionalized cyclopentene derivatives in high yield with wide generality.

PMID- 19860448
TI  - 18O stable isotope labeling, quantitative model experiments, and molecular
      dynamics simulation studies on the trans-specific degradation of the bitter
      tasting iso-alpha-acids of beer.
AB  - The typical bitterness of fresh beer is well-known to decrease in intensity and
      to change in quality with increasing age. This phenomenon was recently shown to
      be caused by the conversion of bitter tasting trans-iso-alpha-acids into
      lingering and harsh bitter tasting tri- and tetracyclic degradation products such
      as tricyclocohumol, tricyclocohumene, isotricyclocohumene, tetracyclocohumol, and
      epitetracyclocohumol. Interestingly, the formation of these compounds was shown
      to be trans-specific and the corresponding cis-iso-alpha-acids were found to be
      comparatively stable. Application of 18O stable isotope labeling as well as
      quantitative model studies combined with LC-MS/MS experiments, followed by
      computer-based molecular dynamics simulations revealed for the first time a
      conclusive mechanism explaining the stereospecific transformation of trans-iso
      alpha-acids into the tri- and tetracyclic degradation products. This
      transformation was proposed to be induced by a proton-catalyzed carbon/carbon
      bond formation between the carbonyl atom C(1') of the isohexenoyl moiety and the
      alkene carbon C(2'') of the isoprenyl moiety of the trans-iso-alpha-acids.

PMID- 19860449
TI  - Syntheses of quaternary carbon-containing oxazatricycle and spiropyran libraries
      via multicomponent reactions and their molecular switching properties.
AB  - A practical protocol for the preparation of parallel solution-phase libraries of
      the quaternary carbon-containing oxazatricycles and spiropyrans is reported.
      Target compounds were obtained in moderate to excellent yields by an Et(3)N
      mediated multicomponent reaction from various N-methylisoquinolium or flavylium
      salts and 4-hydroxycoumarins or dimedone in acetone. Purification of the final
      products by recrystallization in ethyl acetate/methylene chloride or by column
      chromatography allowed easy isolation of nine compounds of each array.
      Preliminary studies indicated that some of the prepared compounds exhibit redox
      switching, photochromic, and thermochromic properties.

PMID- 19860450
TI  - Measurement of conjugated linoleic acid (CLA) in CLA-rich soy oil by attenuated
      total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR).
AB  - Conjugated linoleic acid (CLA) isomers in oils are currently measured as fatty
      acid methyl esters by a gas chromatography-flame ionization detector (GC-FID)
      technique, which requires approximately 2 h to complete the analysis. Hence, we
      aim to develop a method to rapidly determine CLA isomers in CLA-rich soy oil. Soy
      oil with 0.38-25.11% total CLA was obtained by photo-isomerization of 96 soy oil
      samples for 24 h. A sample was withdrawn at 30 min intervals with repeated
      processing using a second batch of oil. Six replicates of GC-FID fatty acid
      analysis were conducted for each oil sample. The oil samples were scanned using
      attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR),
      and the spectrum was collected. Calibration models were developed using partial
      least-squares (PLS-1) regression using Unscrambler software. Models were
      validated using a full cross-validation technique and tested using samples that
      were not included in the calibration sample set. Measured and predicted total
      CLA, trans,trans CLA isomers, total mono trans CLA isomers, trans-10,cis-12 CLA,
      trans-9,cis-11 CLA and cis-10,trans-12 CLA, and cis-9,trans-11 CLA had cross
      validated coefficients of determinations (R2v) of 0.97, 0.98, 0.97, 0.98, 0.97,
      and 0.99 and corresponding root-mean-square error of validation (RMSEV) of 1.14,
      0.69, 0.27, 0.07, 0.14, and 0.07% CLA, respectively. The ATR-FTIR technique is a
      rapid and less expensive method for determining CLA isomers in linoleic acid
      photo-isomerized soy oil than GC-FID.

PMID- 19860451
TI  - Corn steep liquor as a nutrition adjunct for the production of Aspergillus niger
      lipase and hydrolysis of oils thereof.
AB  - Corn steep liquor (CSL) has been used as a nutrition adjunct for the production
      of an extracellular lipase from Aspergillus niger, which has immense importance
      as an additive in laundry detergent formulations. A five-level four-factorial
      central composite design was chosen to determine the optimal medium components
      with four critical variables, namely, CSL, NH4H2PO4, Na2HPO4, and sesame oil,
      that were found to be influential for lipase production by the classical one
      factor-at-a-time method. The model suggested that all of the factors chosen had a
      significant impact on lipase production, and the optimum values of the
      influential parameters were CSL, 2.0%, w/v; NH4H2PO4, 0.05%, w/v; Na2HPO4, 0.75%,
      w/v; and sesame oil, 2.0%, w/v, with an activity of 26.7 U/mL at 48 h and 30
      degrees C, which was 2.16-fold higher than the initial activity (12 U/mL)
      obtained by the conventional one-factor-at-a-time method. Furthermore, the enzyme
      has good potential for the hydrolysis of vegetable oils and fish oils, and a
      hydrolytic ratio of 88.73% was obtained with palm oil at 48 h. The utilization of
      CSL and sesame oil for lipase production from A. niger makes the process green,
      because both are renewable substrates and economically viable at an industrial
      scale.

PMID- 19860452
TI  - Interfacial-energy-controlled deposition technique of microstructures using blade
      coating.
AB  - A novel blade-coating technique for the fluidic self-assembly of microstructures
      on large-scale substrates is presented. In our blade-coating technique, water and
      microstructures dispersion, which includes chemically modified microstructures
      and water-insoluble solvent, are continuously blade-coated on a substrate on
      which surface hydrophilic areas are surrounded by a hydrophobic self-assembled
      monolayer. In the process studied, first, water is selectively placed on the
      hydrophilic areas; second, the water-insoluble solvent covers the water to create
      a solvent/water interface; third, fluidic self-assembly of microstructures onto
      the water takes place by a capillary force between the water and the
      microstructures; and finally, the microstructures are deposited onto the
      hydrophilic areas after the evaporation of the water and the solvent. SiO(2)
      plates sized 10 x 50 x 0.3 microm(3) were used to verify the feasibility of our
      technique. About 40,000 SiO(2) plates were selectively deposited on the
      hydrophilic areas on a substrate with an area of 20 cm(2) with a deposition
      probability of 0.52 by utilizing dispersion consisting of plates chemically
      modified with 1-chloroethyltrichlorosilane and a mixture of 1,4-dichlorobutane
      and n-hexane. The deposition probabilities of the plates primarily depended on
      the type of solvent for plate dispersions and increased with an increase in the
      value of free energy change of the plate/solvent/water system by the movement of
      the plate from the solvent to the solvent/water interface during the blade
      coating process. These results indicate that the deposition probabilities are
      governed directly by the capillary force acting on the plates. Our deposition
      technique for microstructures using blade-coating is potentially applicable to
      the deposition of micrometer-size electronic devices on large-scale substrates.

PMID- 19860453
TI  - Intracellular processing of proteins mediated by biodegradable polyelectrolyte
      capsules.
AB  - Multilayer polyelectrolyte capsules made by layer-by-layer assembly of oppositely
      charged biodegradable polyelectrolytes were filled with a model of a nonactive
      prodrug, a self-quenched fluorescence-labeled protein. After capsule uptake by
      living cells, the walls of the capsules were actively degraded and digested by
      intracellular proteases. Upon capsule wall degradation, intracellular proteases
      could reach the protein cargo in the cavity of the capsules. Enzymatic
      fragmentation of the self-quenched fluorescence-labeled protein by proteases led
      to individual fluorescence-labeled peptides and thus revoked self-quenching of
      the dye. In this way nonactive (nonfluorescent) molecules were converted into
      active (fluorescent) molecules. The data demonstrates that biodegradable capsules
      are able to convert nonactive molecules (prodrugs) to active molecules (drugs)
      specifically only inside cells where appropriate enzymes are at hand. In this way
      only cargo inside the capsules reaching cells is activated, but not the cargo in
      capsules which remain extracellular. The peptide fragments undergo further
      processing inside the cells, leading ultimately to exocytosis.

PMID- 19860454
TI  - Kinetically induced kinking of vapor-liquid-solid grown epitaxial si nanowires.
AB  - Epitaxial Si nanowires grown from Au seeds using the vapor-liquid-solid method
      begin growing normal to the Si(111) substrate atop a tapered base. After a
      kinetically determined length, the NWs may kink away from [111] to another
      crystallographic direction. The smallest NWs prefer growth along 110 while larger
      Si NWs choose either 111 or 112 based on whether growth conditions favor Au-free
      sidewalls. "Vertical" growth normal to the Si(111) substrate is obtained only for
      slowly growing NWs with Au-decorated sidewalls. At the fastest growth rates,
      single-crystal Si NWs smoothly, continuously, and randomly vary their growth
      directions, producing a morphology that is qualitatively different than highly
      kinked growth.

PMID- 19860455
TI  - Fate of excitations in conjugated polymers: single-molecule spectroscopy reveals
      nonemissive "dark" regions in MEH-PPV individual chains.
AB  - Single chains of the conjugated polymer MEH-PPV (poly(2-methoxy-5-(2'
      ethylhexyloxy)-1,4-phenylenevinylene)) were studied with wide-field fluorescence
      microscopy (dispersion in inert polymer matrices) and with fluorescence
      correlation spectroscopy (chloroform solution). The fluorescence yield of
      individual molecules in matrices was found to be 1-2 orders of magnitude lower
      than that in solution and it decreased substantially with increasing chain
      length. It suggests that isolation of MEH-PPV molecules in polymer matrices
      creates favorable conditions for photogeneration of nonemissive primary excited
      states.

PMID- 19860456
TI  - Oxalate bridged MM (MM = Mo2, MoW, and W2) quadruply bonded complexes as test
      beds for current mixed valence theory: looking beyond the intervalence charge
      transfer transition.
AB  - The spectroscopic features of a series of oxalate bridged complexes
      [((t)BuCO(2))(3)MM](2)-mu(2)-O(2)CCO(2) (where MM = Mo(2), MoW, and W(2)) in
      their neutral and singly oxidized (mixed valence) states are examined as a
      function of temperature and solvent. A large degree of electronic coupling
      between the two MM centers is evident, principally involving the MM delta
      orbitals mediated by the oxalate bridge pi* orbital. In the oxidized states these
      mixed valence ions show solvent independent intervalence charge transfer
      (alternatively termed charge resonance) bands, consistent with assignment to
      Class III (or electronically delocalized) within the Robin-Day classification
      scheme. In both the neutral and oxidized states these complexes also show an
      intense metal-to-ligand charge-transfer (MLCT) transition, involving the lowest
      unoccupied molecular orbital (LUMO) of the bridge. The solvent and temperature
      dependence of this transition is also reported along with an inspection and
      simulation of the vibronic features, which are notably altered when switching
      between the neutral and the mixed valence states as well as with variation of the
      nature of the MM unit. Collectively, these observations allow us to comment on
      the validity and limitations of current theories dealing with mixed valence ions
      that have hitherto ignored the information that can be gained from MLCT
      transitions.

PMID- 19860457
TI  - Syntheses, characterization, and computational study of WSF4 and WSF4 x CH3CN.
AB  - A new and improved synthetic route to WSF(4) was developed from the reaction of
      WF(6) and Sb(2)S(3) in anhydrous HF. Tungsten sulfide tetrafluoride was
      characterized by Raman and (19)F NMR spectroscopy for the first time in HF
      solvent. Both studies provided evidence for its monomeric form in HF solution. In
      the solid state, WSF(4) was also characterized by Raman and infrared
      spectroscopy. The WSF(4) x CH(3)CN adduct was prepared from WSF(4) and CH(3)CN in
      anhydrous HF solvent and by the direct combination of WSF(4) with excess CH(3)CN,
      and was characterized by Raman and infrared spectroscopy in the solid state and
      (19)F NMR spectroscopy in CH(3)CN solution. The crystal structure of WSF(4) x
      CH(3)CN was obtained and showed that CH(3)CN coordinates to W in an end-on
      fashion and trans to the W-S bond. Quantum-chemical calculations using B3LYP and
      PBE1PBE methods were used to calculate the gas-phase geometries and vibrational
      frequencies of WSF(4) and WSF(4) x CH(3)CN.

PMID- 19860458
TI  - Synthesis and Mossbauer characterization of octahedral iron(II) carbonyl
      complexes FeI2(CO)3L and FeI2(CO)2L2: developing models of the [Fe]-H(2)ase
      active site.
AB  - A series of mono- and disubstituted complexes, FeI(2)(CO)(x)L(4-x), x = 2 or 3,
      is conveniently accessed from simple mixing of N-heterocyclic carbenes,
      phosphines, and aromatic amines with FeI(2)(CO)(4), first reported by Hieber in
      1928. The highly light sensitive complexes yield to crystallization and X-ray
      diffraction studies for six complexes showing them to be rudimentary structural
      models of the monoiron hydrogenase, [Fe]-H(2)ase or Hmd, active site in native
      (Fe(II)(CO)(2)) or CO-inhibited (Fe(II)(CO)(3)) states. Diatomic ligand (nu(CO))
      vibrational and Mossbauer spectroscopies are related to those reported for the
      Hmd active site. The importance of a serial approach for relating such parameters
      in model compounds to low spin Fe(II) in the diverse ligation of enzyme active
      sites is stressed.

PMID- 19860459
TI  - Base-catalyzed insertion of dioxygen into rhodium-hydrogen bonds: kinetics and
      mechanism.
AB  - The reaction between molecular oxygen and rhodium hydrides L(OH)RhH(+) (L =
      (NH(3))(4), trans-L(1), and cis-L(1), where L(1) = cyclam) in basic aqueous
      solutions rapidly produces the corresponding hydroperoxo complexes. Over the pH
      range 8 < pH < 12, the kinetics exhibit a first order dependence on [OH(-)]. The
      dependence on [O(2)] is less than first order and approaches saturation at the
      highest concentrations used. These data suggest an attack by OH(-) at the hydride
      with k = (1.45 +/- 0.25) x 10(3) M(-1) s(-1) for trans-L(1)(OH)RhH(+) at 25
      degrees C, resulting in heterolytic cleavage of the Rh-H bond and formation of a
      reactive Rh(I) intermediate. A competition between O(2) and H(2)O for Rh(I) is
      the source of the observed dependence on O(2). In support of this mechanism,
      there is a significant kinetic isotope effect for the initial step,
      L(1)(OH(D))RhH(D)(+) + OH(D)(-) k(1)/k(-1) L(1)(OH(D))Rh(I) + H(D)(2)O,
      k(1H)/k(1D) = 1.7, and k(-1H)/k(-1D) = 3.0. The activation parameters for k(1)
      for trans-L(1)(OH)RhH(+) are DeltaH(++) = 64.6 +/- 1.3 kJ mol(-1) and DeltaS(++)
      = 40 +/-4 J mol(-1) K(-1).

PMID- 19860461
TI  - The role of torsion/torsion coupling in the vibrational spectrum of cis-cis
      HOONO.
AB  - A three-dimensional model of the vibrational dynamics of HOONO is investigated.
      This model focuses on the couplings between the OH stretch vibration and the two
      torsions. The model is based on electronic energies, calculated at the CCSD(T)/cc
      pVTZ level of theory and basis and dipole moment functions calculated at the
      CCSD/aug-cc-pVDZ level. The resulting points were fit to explicit functional
      forms, and the energies, wave functions, and intensities were evaluated using an
      approach in which the OH stretching motion was adiabatically separated from the
      torsional modes. It is found that the HOON torsion is strongly coupled to both
      the OONO torsion and OH stretch. Despite this, many of the conclusions that were
      drawn from earlier two-dimensional treatments, which did not include the OONO
      torsion, hold up on a semiquantitative level. In addition, we use this model to
      investigate the assignment of recently reported matrix isolated spectra of HOONO
      and DOONO. Finally, by comparing the results of this three-dimensional
      calculation to two-dimensional calculations and to the results of second-order
      perturbation theory, we investigate the question of how one determines the size
      of the reduced-dimensional system that is needed to describe the vibrational
      spectrum of molecules, like HOONO, that contain several large amplitude motions.

PMID- 19860460
TI  - Synthesis of [n,5]-spiroketals by ring enlargement of donor-acceptor-substituted
      cyclopropane derivatives.
AB  - Exocyclic enol ethers served as starting materials for the synthesis of [n,5]
      spiroketals (n = 5, 6). A metal-mediated cyclopropanation using ethyl
      diazoacetate afforded spiroannelated cyclopropane derivatives bearing an ester
      group. A reduction of the corresponding ester by LiAlH(4), followed by subsequent
      oxidation using hypervalent iodine reagents, produced [n,5]-spiroketals in
      moderate to good yields. The key step within this three-step sequence is the ring
      enlargement of the three-membered ring with an oxygen donor and a carbonyl
      acceptor group into the five-membered enol ether system. Catalytic amounts of the
      Lewis acid Yb(OTf)(3) facilitate the ring enlargement and increase the yield of
      the corresponding spiroketal in many cases. When Yb(OTf)(3) was used, our
      experiments revealed an open transition state rather than a concerted mechanism
      because the stereochemistry of the spirocenter was not conserved during the ring
      enlargement. As a result, the thermodynamically more favored anomeric [n,5]
      spiroketal was observed as the major product. All the structures were established
      unambiguously by NOESY experiments.

PMID- 19860462
TI  - Interfacial reactivity of "on water" reactions in the presence of alcoholic
      cosolvents.
AB  - A detailed study of the variation in the interfacial reactivity and selectivity
      of "on water" reactions in the presence of increasing amounts of alcoholic
      cosolvents is discussed in the present work. The initial increase in the rates of
      "on water" reactions on the addition of alcoholic cosolvents is contrary to the
      sharp decrease in rates observed for homogeneous aqueous reactions. The existing
      theoretical framework is presented in terms of a typical "on water" process to
      enable a discussion of the experimental observations with reference to changing
      composition of the reaction medium. On the basis of the interesting observations
      of reactivity and selectivity variations with composition of the reaction medium,
      a simple "signature" characteristic for "on water" reactions is proposed.

PMID- 19860463
TI  - CH4 activation by W atom in the gas phase: a case of two-state reactivity
      process.
AB  - Gas-phase methane activation by tungsten (W) atoms was studied at the density
      functional level of theory using the hybrid exchange correlation functional
      B3LYP. Four reaction profiles corresponding to the septet, quintet, triplet, and
      singlet multiplicities were investigated in order to ascertain the presence of
      some spin inversion during the methane activation. Methane activation mediated by
      W atoms was found to be a spin-forbidden process resulting from the crossing
      among the multistate energetic profiles. On the basis of the Hammond postulate,
      this is a typical two-state reactivity (TSR) reaction. The minimum energy
      crossing points lead to decrease in the barrier heights of TS01, TS12, TS23, and
      TS24 that correspond to the first, second, and third hydrogen transfer and the
      reductive elimination step of H(2), respectively. The spin-orbit coupling is
      calculated between electronic states of different multiplicities at the crossing
      points (MECPs) to estimate the intersystem crossing probabilities, and the
      probability of hopping from one surface to the other in the vicinity of the
      crossing region is calculated by the Landau-Zener type model.

PMID- 19860464
TI  - Facile and scalable route for highly efficient enrichment of semiconducting
      single-walled carbon nanotubes.
AB  - Purely semiconducting single-walled carbon nanotubes (s-SWNTs) with a narrow
      diameter distribution have been produced for HiPco SWNTs. A facile technique
      combining microwave irradiation with mixed-acid-assisted dispersion has proven
      efficient for enrichment of s-SWNTs. Using this process, both electronic type
      dependent (metallic versus semiconducting) and diameter-dependent separation of
      SWNTs were simultaneously realized. By mildly controlling experimental
      conditions, metallic single-walled carbon nanotubes (m-SWNTs) and smaller s-SWNTs
      were preferentially removed, yielding purely diameter distribution-narrowed
      semiconducting nanotubes. Furthermore, the chemical structure of carbon nanotubes
      was restored after thermal annealing, as indicated by Raman and UV absorption
      investigations. The dual effects of semiconducting enrichment and diameter
      distribution narrowing, along with facile procedures, make this method promising
      for large-scale separation of SWNTs and therefore for industrial fabrication of
      nanotube-based electronics.

PMID- 19860465
TI  - Mechanistic studies on Ni(dppe)Cl(2)-catalyzed chain-growth polymerizations:
      evidence for rate-determining reductive elimination.
AB  - The mechanisms for Ni(dppe)Cl(2)-catalyzed chain-growth polymerization of 4-bromo
      2,5-bis(hexyloxy)phenylmagnesium chloride and 5-bromo-4-hexylthiophen-2
      ylmagnesium chloride were investigated. Rate studies utilizing IR spectroscopy
      and gas chromatography revealed that both polymerizations exhibit a first-order
      dependence on the catalyst concentration but a zeroth-order dependence on the
      monomer concentration. (31)P NMR spectroscopic studies of the reactive
      organometallic intermediates suggest that the resting states are unsymmetrical
      Ni(II)-biaryl and Ni(II)-bithiophene complexes. In combination, the data
      implicate reductive elimination as the rate-determining step for both monomers.
      Additionally, LiCl was found to have no effect on the rate-determining step or
      molecular weight distribution in the arene polymerization.

PMID- 19860466
TI  - From 2-fold completive to integrative self-sorting: a five-component
      supramolecular trapezoid.
AB  - The amalgamation of two incomplete self-sorting processes into a process that
      makes quantitative use of all members of the library is described by 2-fold
      completive self-sorting. Toward this goal, individual metal-ligand binding
      scenarios were optimized for high thermodynamic stability and best selectivity,
      by screening a variety of factors, such as steric and electronic effects, pi-pi
      interactions, and metal-ion specifics. Using optimized, heteroleptic metal-ligand
      binding motifs, a library of four different ligands (1, 2, 3, 4) and two
      different metal ions (Zn(2+), Cu(+)) was set up to assess 2-fold completive self
      sorting. Out of 20 different combinations, the self-sorting library ended up with
      only two metal-ligand complexes in basically quantitative yield. To demonstrate
      the value of 2-fold completive self-sorting for the formation of nanostructures,
      the optimized, highly selective binding motifs were implemented into three
      polyfunctional ligands. Their integrative self-sorting in the presence of Zn(2+)
      and Cu(+) led to the clean formation of the supramolecular trapezoid T, a simple
      but still unknown supramolecular architecture. The dynamic trapezoid T consists
      of three different ligands with four different donor-acceptor interactions. Its
      structure was established by (1)H NMR spectroscopy, electrospray ionization mass
      spectroscopy, and differential pulse voltammetry (DPV) and by exclusion of
      alternative structures.

PMID- 19860467
TI  - Development and in-house validation of the event-specific polymerase chain
      reaction detection methods for genetically modified soybean MON89788 based on the
      cloned integration flanking sequence.
AB  - Various polymerase chain reaction (PCR) methods were developed for the execution
      of genetically modified organism (GMO) labeling policies, of which an event
      specific PCR detection method based on the flanking sequence of exogenous
      integration is the primary trend in GMO detection due to its high specificity. In
      this study, the 5' and 3' flanking sequences of the exogenous integration of
      MON89788 soybean were revealed by thermal asymmetric interlaced PCR. The event
      specific PCR primers and TaqMan probe were designed based upon the revealed 5'
      flanking sequence, and the qualitative and quantitative PCR assays were
      established employing these designed primers and probes. In qualitative PCR, the
      limit of detection (LOD) was about 0.01 ng of genomic DNA corresponding to 10
      copies of haploid soybean genomic DNA. In the quantitative PCR assay, the LOD was
      as low as two haploid genome copies, and the limit of quantification was five
      haploid genome copies. Furthermore, the developed PCR methods were in-house
      validated by five researchers, and the validated results indicated that the
      developed event-specific PCR methods can be used for identification and
      quantification of MON89788 soybean and its derivates.

PMID- 19860468
TI  - Red mold rice promoted antioxidase activity against oxidative injury and improved
      the memory ability of zinc-deficient rats.
AB  - Zn deficiency is a common disease leading to memory impairment with increasing
      age. This study evaluated the protection effects of red mold rice (RMR)
      administration and Zn supplementation against memory and learning ability
      impairments from oxidative stress caused by Zn deficiency. Rats (4 weeks old)
      were induced to be Zn deficiency by a Zn-deficient diet for 12 weeks. After that,
      rats were administered Zn, 1xRMR, 5xRMR, and various dosages of RMR plus Zn,
      respectively. Decreases of antioxidant enzyme activities in the hippocampus and
      cortex were observed, and the levels of Ca, Fe, and Mg were increased in the
      hippocampus and cortex of Zn-deficient rats, leading to memory and learning
      ability injury. However, the administration of RMR (1- or 5-fold dosage) and with
      or without Zn significantly improved the antioxidase and neural activity to
      maintain cortex and hippocampus functions. This study demonstrates that RMR is a
      possible functional food for the prevention or cure of neural injury associated
      with Zn deficiency.

PMID- 19860469
TI  - Identification of extensin protein associated with sugar beet pectin.
AB  - Several studies have suggested that the emulsification properties associated with
      pectin obtained from sugar beet (Beta vulgaris) are due to the presence of a
      protein-pectin complex. Nevertheless, the identity of the protein has remained
      elusive. Pectin, extracted from sugar beet pulp by microwave-assisted extraction,
      and a commercial sample were both subjected to protease digestion with trypsin.
      The resulting peptides were separated from the pectin solution by ultrafiltration
      using a 3 kDa molecular weight cutoff (MWCO) membrane and analyzed using matrix
      assisted laser desorption ionization with tandem time-of-flight mass
      spectrometry. The partial sequences derived from the mass spectrometry analyses
      of the resulting tryptic peptides are found to be highly consistent with extensin
      protein matched from the B. vulgaris Genetic Index database and also correspond
      to previously reported extensin peptides found in sugar beet cell suspension
      cultures. Further attempts were made to disassociate the protein from pectin
      using 1 M NaCl and a 100 kDa MWCO membrane; however, no peptides were observed
      following trypsin digestion of the permeate solution. This evidence suggests the
      existence of a complex between the pectin and extensin that is not due to ionic
      interactions. Trypsin digestion of commercial sugar beet pectin also produced the
      peptide profile observed with the microwave-assisted extracted pectin sample.
      Atomic force microscopy established that the number of rod-like elements
      decreased following protease treatment compared to the untreated sample.

PMID- 19860470
TI  - Rapid detection and differentiation of Alicyclobacillus species in fruit juice
      using hydrophobic grid membranes and attenuated total reflectance infrared
      microspectroscopy.
AB  - Pasteurized juices may undergo spoilage during normal shelf life due to
      Alicyclobacillus spp. Metabolic byproducts during germination of these
      thermoacidiophilic, endospore-forming bacteria impart off-flavors. The objective
      was to develop a simple, rapid, and sensitive approach for differentiation of
      Alicyclobacillus spp. by attenuated total reflectance infrared (ATR-IR)
      microspectroscopy after isolation onto hydrophobic grid membrane (HGM) filters.
      Dilutions of four different species of Alicyclobacillus were filtered onto HGM,
      incubated on orange serum agar (50 degrees C, 36-48 h), and dried under vacuum.
      Spectra were collected using ATR-IR microspectroscopy and analyzed by
      multivariate analysis. Results indicated that soft independent modeling of class
      analogy models exhibited clusters that permitted classification at species and
      strain levels. The methodology was validated by correctly predicting
      Alicyclobacillus (100%) in blind tests. The proposed procedure permits chemically
      based classification of intact microbial cells. Implementation provides the juice
      industry with a rapid screening procedure to detect and monitor Alicyclobacillus
      that threatens the quality of pasteurized juices.

PMID- 19860471
TI  - Critical role of tryptophan 154 for the activity and stability of class D beta
      lactamases.
AB  - The catalytic efficiency of the class D beta-lactamase OXA-10 depends critically
      on an unusual carboxylated lysine as the general base residue for both the enzyme
      acylation and deacylation steps of catalysis. Evidence is presented that the
      interaction between the indole group of Trp154 and the carboxylated lysine is
      essential for the stability of the posttranslationally modified Lys70.
      Substitution of Trp154 by Gly, Ala, or Phe yielded noncarboxylated enzymes which
      displayed poor catalytic efficiencies and reduced stability when compared to the
      wild-type OXA-10. The W154H mutant was partially carboxylated. In addition, the
      maximum values of k(cat) and k(cat)/K(M) were shifted toward pH 7, indicating
      that the carboxylation state of Lys70 is dependent on the protonation level of
      the histidine. A comparison of the three-dimensional structures of the different
      proteins also indicated that the Trp154 mutations did not modify the overall
      structures of OXA-10 but induced an increased flexibility of the Omega-loop in
      the active site. Finally, the deacylation-impaired W154A mutant was used to
      determine the structure of the acyl-enzyme complex with benzylpenicillin. These
      results indicate a role of the Lys70 carboxylation during the deacylation step
      and emphasize the importance of Trp154 for the ideal positioning of active site
      residues leading to an optimum activity.

PMID- 19860472
TI  - Buffers may adversely affect model lipid membranes: a cautionary tale.
AB  - The effects of biological buffers on lipids have not been fully investigated
      because of the long-standing assumption that these buffers are too hydrophilic to
      substantially interact with the lipid membrane. We present evidence that for some
      buffers, this is not necessarily the case. Our research points toward a membrane
      softening effect caused by the buffer molecules interacting with the headgroup
      region of the lipid. Changes in the elastic properties of the membrane are known
      to control membrane protein behavior; this work serves as a warning for the
      design of assays utilizing model membranes in the presence of buffers.

PMID- 19860473
TI  - Repression of translation of human estrogen receptor alpha by G-quadruplex
      formation.
AB  - Tissue-specific expression of the human estrogen receptor alpha gene (ESR1) is
      achieved through multiple promoter sequences resulting in various mRNA
      transcripts encoding a common protein but differing in their 5'-untranslated
      region (5'-UTR). Many cancers are estrogen-sensitive with neoplastic growth
      stimulated through the estrogen receptor, a transcription factor that regulates
      developmental genes. We demonstrate that the human ESR1 gene is rich in potential
      quadruplex-forming sequences with 3 of 20 identified within exonic regions. In
      particular, we show using CD, UV, and NMR spectroscopy that a stable DNA G
      quadruplex motif is formed within the exon C gene sequence. This motif, which PCR
      shows is transcribed in normal and neoplastic endometrium and in MCF-7 cells,
      forms a stable RNA quadruplex demonstrable by CD and UV analysis. Cloning the
      exon C G-quadruplex sequence upstream of a luciferase reporter gene caused a 6
      fold reduction of enzymatic activity compared to a mutant sequence. We conclude
      that the exon C G-quadruplex motif is present in the 5'-UTR of the mRNA
      transcript, where it modulates the efficiency of translation.

PMID- 19860474
TI  - Low-temperature, highly selective, gas-phase oxidation of benzyl alcohol over
      mesoporous K-Cu-TiO2 with stable copper(I) oxidation state.
AB  - A newly developed mesoporous mixed metal oxide (K-Cu-TiO(2)) catalyst is capable
      of highly selective, gas-phase benzyl alcoholbenzaldehyde transformation at
      excellent yields (>99%) under surprisingly low temperatures (203 degrees C, bp of
      benzyl alcohol). The low-temperature reaction conditions and integration of K and
      Cu(I) components into the TiO(2) matrix are of vital importance for the
      stabilization of an active Cu(I) oxidation state and resultant stable, excellent
      catalytic performance.

PMID- 19860475
TI  - Reaction of a redox-active ligand complex of nickel with dioxygen probes ligand
      radical character.
AB  - Bis(imino)pyridine complex [Ni{2,6-(ArN=CMe)(2)C(5)H(3)N}Cl] (where Ar = 2,6
      (i)Pr(2)C(6)H(3)) was synthesized by reduction of the corresponding dichloride
      complex and characterized as a ligand-radical complex of Ni(II). Reaction of this
      complex with O(2) caused intraligand C-C bond cleavage to afford the Ni complex
      of the new iminoethylpyridylcarboxamidato ligand, which also was isolated as the
      corresponding carboxamide, 6-(ArN=CMe)C(5)H(3)N-2-C(O)NHAr. This reaction serves
      as an example of small-molecule activation effected directly at the redox-active
      bis(imino)pyridine ligand without an overall oxidation state change at the Ni
      center.

PMID- 19860476
TI  - RDC enhanced NMR spectroscopy in organic solvent media: the importance for the
      experimental determination of periodic hydrogen bonded secondary structures.
AB  - Precise NMR structural determination of distinct hydrogen-bonded secondary folds
      in unnatural peptides is demonstrated by using residual dipolar couplings (RDCs),
      measured in organic solvent media. The results show that the conventional
      constraints, (3)J(HH) and NOE-derived distances alone do not allow the accurate
      structural elucidation even for rigid foldamers and emphasize the need of RDC
      based structure validation and refinement for unnatural peptides in particular
      and small organic molecules in general.

PMID- 19860477
TI  - Spectroscopic characterization of YedY: the role of sulfur coordination in a
      Mo(V) sulfite oxidase family enzyme form.
AB  - Electronic paramagnetic resonance (EPR), electronic absorption, and magnetic
      circular dichroism spectroscopies have been performed on YedY, a SUOX fold
      protein with a Mo domain that is remarkably similar to that found in chicken
      sulfite oxidase, Arabidopsis thaliana plant sulfite oxidase, and the bacterial
      sulfite dehydrogenase from Starkeya novella. Low-energy dithiolene --> Mo and
      cysteine thiolate --> Mo charge-transfer bands have been assigned for the first
      time in a Mo(V) form of a SUOX fold protein, and the spectroscopic data have been
      used to interpret the results of bonding calculations. The analysis shows that
      second coordination sphere effects modulate dithiolene and cysteine sulfur
      covalency contributions to the Mo bonding scheme. In particular, a more acute
      O(oxo)-Mo-S(Cys)-C dihedral angle results in increased cysteine thiolate S --> Mo
      charge transfer and a large g(1) in the EPR spectrum. The spectrosocopic results,
      coupled with the available structural data, indicate that these second
      coordination sphere effects may play key roles in modulating the active-site
      redox potential, facilitating hole superexchange pathways for electron transfer
      regeneration, and affecting the type of reactions catalyzed by sulfite oxidase
      family enzymes.

PMID- 19860478
TI  - Probing interfacial electron transfer in coumarin 343 sensitized TiO2
      nanoparticles with femtosecond stimulated Raman.
AB  - Femtosecond Stimulated Raman Spectroscopy (FSRS) is used as a structural probe of
      the interfacial electron transfer between Coumarin 343, a solar cell sensitizer,
      and TiO(2) nanoparticles. Resonance Raman spectra of the charge-transfer complex
      reveals multiple vibrational motions, consisting primarily of carbon backbone and
      Ti-O binding modes, that direct the molecule out of the Franck-Condon region on
      the excited state potential energy surface. The vibrational spectrum and decay
      dynamics of the radical cation are also reported. These spectra indicate that the
      hole is localized on the conjugated carbon rings and that the donation mechanism
      involves multiple vibrational motions. We conclude with a discussion of prospects
      for improving the solar cell sensitization properties of Coumarin 343 through
      structural modification.

PMID- 19860479
TI  - Understanding ground- and excited-state properties of perylene tetracarboxylic
      acid bisimide crystals by means of quantum chemical computations.
AB  - Quantum chemical protocols explaining the crystal structures and the visible
      light absorption properties of 3,4:9,10-perylene tetracarboxylic acid bisimide
      (PBI) derivates are proposed. Dispersion-corrected density functional theory has
      provided an intermolecular potential energy of PBI dimers showing several
      energetically low-lying minima, which corresponds well with the packing of
      different PBI dyes in the solid state. While the dispersion interaction is found
      to be crucial for the binding strength, the minimum structures of the PESs are
      best explained by electrostatic interactions. Furthermore, a method is
      introduced, which reproduces the photon energies at the absorption maxima of PBI
      pigments within 0.1 eV. It is based on time-dependent Hartree-Fock (TD-HF)
      excitation energies calculated for PBI dimers with the next-neighbor arrangement
      in the pigment and incorporates crystal packing effects. This success provides
      clear evidence that the electronically excited states, which determine the color
      of these pigments, have no significant charge-transfer character. The developed
      protocols can be applied in a routine manner to understand and to predict the
      properties of such pigments, which are important materials for organic solar
      cells and (opto-)electronic devices.

PMID- 19860480
TI  - Theoretical characterization of the dynamical behavior and transport properties
      of alpha,gamma-peptide nanotubes in solution.
AB  - We present here a molecular dynamics study on a promising class of peptide
      nanotubes with a partially hydrophobic inner cavity and an easy chemical
      functionalization of the lumen of the cylindrical structure. The structural and
      dynamical behavior of the nanotube in water, methanol, and chloroform has been
      analyzed using state of the art theoretical methods. The nanotube structure is
      always well preserved, but solvent-dependent dynamic alterations are evident.
      Such dynamic effects are surprisingly more severe in the most viscous solvent
      (water), as a consequence of the competition in polar solvents between intra- and
      intermolecular hydrogen bonds. Stiffness analysis from the collected trajectories
      helped us to characterize the equilibrium deformability of the nanotube, while
      steered dynamics simulations were used to determine the magnitude of free energy
      associated with nanotube growth. Analysis of the carrier and permeation
      properties of the compounds reveals surprising properties: (i) permeability for
      the most polar solvent (water), (ii) carrier properties for the most apolar
      solvent (chloroform), and (iii) neither good permeation nor carrier properties
      for the intermediate solvent in polarity (methanol). Results reported here
      constitute the most extensive characterization of these nanotubes presented to
      date and open many intriguing questions on their stability, dynamics, and
      transport/carrier properties.

PMID- 19860481
TI  - Selective labeling of living cells by a photo-triggered click reaction.
AB  - Phototriggering of the metal-free azide to acetylene cycloaddition reaction was
      achieved by masking the triple bond of dibenzocyclooctynes as cyclopropenone.
      Such masked cyclooctynes do not react with azides in the dark. Irradiation of
      cyclopropenones results in the efficient (Phi(355) = 0.33) and clean regeneration
      of the corresponding dibenzocyclooctynes, which then undergo facile catalyst-free
      cycloadditions with azides to give corresponding triazoles under ambient
      conditions. In situ light activation of a cyclopropenone linked to biotin made it
      possible to label living cells expressing glycoproteins containing N-azidoacetyl
      sialic acid. The cyclopropenone-based phototriggered click chemistry offers
      exciting opportunities to label living organisms in a temporally and spatially
      controlled manner and may facilitate the preparation of microarrays.

PMID- 19860482
TI  - Proton transfer in guanine-cytosine radical anion embedded in B-form DNA.
AB  - The electron-attachment-induced proton transfer in the guanine-cytosine (G:C)
      base pair is thought to be relevant to the issues of charge transport and
      radiation damage in DNA. However, our understanding on the reaction mainly comes
      from the data of isolated bases and base pairs, and the behavior of the reaction
      in the DNA duplex is not clear. In the present study, the proton-transfer
      reaction in reduced G:C stacks is investigated by quantum mechanical calculations
      with the aim to clarify how each environmental factor affects the proton transfer
      in G:C(*-). The calculations show that while the proton transfer in isolated
      G:C(*-) is exothermic with a small energetic barrier, it becomes endothermic with
      a considerably enhanced energetic barrier in G:C stacks. The substantial effect
      of G:C stacking is proved to originate from the electrostatic interactions
      between the dipole moments of outer G:C base pairs and the middle G:C(*-) base
      pair radical anion; the extent of charge delocalization is very small and plays
      little role in affecting the proton transfer in G:C(*-). On the basis of the
      electrostatic model, the sequence dependence of the proton transfer in the
      ionized G:C base pair is predicted. In addition, the water molecules in the first
      hydration shell around G:C(*-) display a pronounced effect that facilitates the
      proton-transfer reaction; further consideration of bulk hydration only slightly
      lowers the energetic barrier and reaction energy. We also notice that the water
      arrangement around an embedded G:C(*-) is different from that around an isolated
      G:C(*-), which could result in a very different solvent effect on the energetics
      of the proton transfer. In contrast to the important influences of base stacking
      and hydration, the effects of sugar-phosphate backbone and counterions are found
      to be minor. Our calculations also reveal that a G:C base pair embedded in DNA is
      capable of accommodating two excess electrons only in bulk hydration; the
      resultant G(N1-H)(-):C(N3+H)(-) dianion is stable and exists long enough to lead
      to DNA damage. The combination of the present results with the previous findings
      in literature suggests that the behaviors of charge transport and low-energy
      electron-induced damage in DNA are highly susceptible to the hydration level.

PMID- 19860484
TI  - A FRET-based method for probing the conformational behavior of an intrinsically
      disordered repeat domain from Bordetella pertussis adenylate cyclase.
AB  - A better understanding of the conformational changes exhibited by intrinsically
      disordered proteins is necessary as we continue to unravel their myriad
      biological functions. In repeats in toxin (RTX) domains, calcium binding triggers
      the natively unstructured domain to adopt a beta roll structure. Here we present
      an in vitro Forster resonance energy transfer (FRET)-based method for the
      investigation of the conformational behavior of an RTX domain from the Bordetella
      pertussis adenylate cyclase consisting of nine repeat units. Equilibrium and
      stopped-flow FRET between fluorescent proteins, attached to the termini of the
      domain, were measured in an analysis of the end-to-end distance changes in the
      RTX domain. The method was complemented with circular dichroism spectroscopy,
      tryptophan fluorescence, and bis-ANS dye binding. High ionic strength was
      observed to decrease the calcium affinity of the RTX domain. A truncation and
      single amino acid mutations yielded insights into the structural determinants of
      beta roll formation. Mutating the conserved Asp residue in one of the nine
      repeats significantly reduced the affinity of the domains for calcium ions.
      Removal of the sequences flanking the repeat domain prevented folding, but
      replacing them with fluorescent proteins restored the conformational behavior,
      suggesting an entropic stabilization. The FRET-based method is a useful technique
      that complements other low-resolution techniques for investigating the dynamic
      conformational behavior of the RTX domain and other intrinsically disordered
      protein domains.

PMID- 19860485
TI  - Integrated metabonomic-proteomic analysis of an insect-bacterial symbiotic
      system.
AB  - The health of animals, including humans, is dependent on their resident
      microbiota, but the complexity of the microbial communities makes these
      associations difficult to study in most animals. Exceptionally, the microbiology
      of the pea aphid Acyrthosiphon pisum is dominated by a single bacterium Buchnera
      aphidicola (B. aphidicola). A (1)H NMR-based metabonomic strategy was applied to
      investigate metabolic profiles of aphids fed on a low essential amino acid diet
      and treated by antibiotic to eliminate B. aphidicola. In addition, differential
      gel electrophoresis (DIGE) with mass spectrometry was utilized to determine the
      alterations of proteins induced by these treatments. We found that these
      perturbations resulted in significant changes to the abundance of 15 metabolites
      and 238 proteins. Ten (67%) of the metabolites with altered abundance were amino
      acids, with nonessential amino acids increased and essential amino acids
      decreased by both perturbations. Over-represented proteins in the perturbed
      treatments included catabolic enzymes with roles in amino acid degradation and
      glycolysis, various cuticular proteins, and a C-type lectin and regucalcin with
      candidate defensive roles. This analysis demonstrates the central role of
      essential amino acid production in the relationship and identifies candidate
      proteins and processes underpinning the function and persistence of the
      association.

PMID- 19860486
TI  - Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and
      insight into the pathophysiology.
AB  - Nuclear magnetic resonance (NMR) spectroscopy and appropriate multivariate
      statistical analyses have been employed on mucosal colonic biopsies, colonocytes,
      lymphocytes, and urine from patients with ulcerative colitis (UC) and controls in
      order to explore the diagnostic possibilities, define new potential biomarkers,
      and generate a better understanding of the pathophysiology. Samples were
      collected from patients with active UC (n = 41), quiescent UC (n = 33), and from
      controls (n = 25) and analyzed by NMR spectroscopy. Data analysis was carried out
      by principal component analysis and orthogonal-projection to latent structure
      discriminant analysis using the SIMCA P+11 software package (Umetrics, Umea,
      Sweden) and Matlab environment. Significant differences between controls and
      active UC were discovered in the metabolic profiles of biopsies and colonocytes.
      In the biopsies from patients with active UC higher levels of antioxidants and of
      a range of amino acids, but lower levels of lipid, glycerophosphocholine (GPC),
      myo-inositol, and betaine were found, whereas the colonocytes only displayed low
      levels of GPC, myo-inositol and choline. Interestingly, 20% of inactive UC
      patients had similar profiles to those who were in an active state. This study
      demonstrates the possibilities of metabonomics as a diagnostic tool in active and
      quiescent UC and provides new insight into pathophysiologic mechanisms.

PMID- 19860488
TI  - Day case cleft lip surgery in Lagos, Nigeria.
AB  - BACKGROUND: The correction of cleft lip deformity has included overnight
      admission and postoperative ward admission from 5 to 7 days. In developing
      countries, increasing cost of treatment and medical insurance and shortage of bed
      space have led to a reduction in the length of hospitalization or its elimination
      for some cases of surgery. OBJECTIVE: To assess the feasibility and complications
      associated with day case cleft lip surgery in our center. METHODS: A prospective
      study of patients undergoing day case cleft lip repair at three hospitals from
      1995 to 2005. RESULTS: A total of 43 patients were seen. Twenty seven (63.8%)
      were treated as day case, and 16 (37.2%) were operated as inpatients. The mean
      age for patients treated as day case was 1.32 +/- 1.45 years. Fifteen (55.6%) of
      these patients had severe associated nasal deformities, six (22.2%) had moderate
      nasal deformity, and four (14.83%) had mild nasal deformity. The only
      complication was a nasovestibular fistula that occurred in one of the day case
      patients. From 27 patients operated on as day cases, eight calls were received.
      Two (7.4%) mothers called to report febrile illness in their children on the
      first postoperative day. Two mothers (7.4%) reported excessive crying. The most
      frequent reason for postoperative consultation was obstruction of the modified
      nasal retainer, which occurred in four patients (14.8%). CONCLUSION: Day case
      surgery for cleft lip can be said to be safe, with a 2.3% rate of complications
      in selected patients. Day case surgery was a cheaper alternative to admission.

PMID- 19860489
TI  - The surgical repair of macrostomia.
AB  - BACKGROUND: Many surgical techniques have been described for the repair of
      macrostomia. However, most were designed for the repair of unilateral
      macrostomia. Most reports of repairs involved small numbers of patients. This has
      not allowed for evaluation of complications and comparison of various techniques.
      OBJECTIVE: This study describes a modification of an older technique designed for
      unilateral macrostomia. Details of the operative technique used for the repair
      are described, along with the principles underlying the various steps. MATERIALS
      AND METHODS: This study involves 13 patients operated for macrostomia using the
      same surgical technique. The patients were seen at a recent screening and mass
      surgery exercise for patients with orofacial and craniofacial deformities.
      RESULTS: Eleven patients had bilateral macrostomia; two had unilateral
      macrostomia. No anesthetic or surgical complications occurred in any of the
      patients. All patients tolerated the procedure well. Oral continence and
      acceptable facial symmetry were restored in all patients, with minimal scarring.

PMID- 19860490
TI  - Saethre-Chotzen syndrome: a case report.
AB  - Saethre-Chotzen syndrome (acrocephalosyndactyly type III) is a craniosynostosis
      syndrome inherited in an autosomal dominant manner. Although similar to the other
      craniosynostosis syndromes in its clinical presentation, this syndrome is caused
      by a mutation in the TWIST1 gene. The TWIST1 gene product is a transcription
      factor containing a basic helix-loop-helix (bHLH) domain important in the
      development of the head and limbs. Clinical features of this syndrome include
      unilateral or bilateral coronal synostosis, ptosis, low-set ears, hearing loss,
      hypertelorism, maxillary hypoplasia, deviated nasal septum, broad great toes,
      clinodactyly, and syndactyly. We report a young girl with clinical features of
      Saethre-Chotzen syndrome who has a previously undescribed sequence variant in the
      TWIST1 gene, corresponding to p.R191M. The location of the altered amino acid in
      the Twist-box of TWIST1, the high conservation of this amino acid between
      different species, and the phenotype of the child all support a pathogenic role
      for this novel TWIST1 sequence alteration.

PMID- 19860491
TI  - Clefts of the secondary palate referred to the Oslo Cleft Team: epidemiology and
      cleft severity in 994 individuals.
AB  - OBJECTIVE: To describe Norwegian individuals born with cleft of the secondary
      palate (CP) in relation to cleft severity, Pierre Robin sequence, associated
      anomalies, syndromes, and hypodontia and to present estimated longitudinal
      prevalences. PATIENTS: Nine hundred ninety-four individuals with CP born between
      1960 and 2002 referred to the Oslo Cleft Team (OCT). METHOD: Data were collected
      retrospectively from the archives of the OCT. RESULTS: Among all CP, 7.6% had
      recognized syndromes, 30.5% had associated anomalies, and in 61.9%, CP was the
      only malformation. Pierre Robin sequence was recorded in 11.7%. Female
      predominance was observed both in general and in each cleft severity subgroup. Of
      610 individuals with CP, only 25.1% were diagnosed with a submucous cleft palate,
      45.9% had a cleft of the soft palate only, and in 29%, the cleft extended into
      the hard palate. Among 309 individuals over the age of 10 years with CP only,
      hypodontia was found in 28.5%, and in individuals with Pierre Robin sequence,
      hypodontia was found in 44.1%. During the period 1965 to 1999, the estimated
      prevalence of individuals with CP in the OCT uptake area was found to be 0.59 per
      1000 live births. The estimated prevalence increased slightly over time, both
      overall and within the cleft severity subgroups. CONCLUSION: A large proportion
      of a Norwegian population with CP had syndrome or additional anomalies. The
      estimated prevalence of CP in this population increased slightly during the
      observation period.

PMID- 19860492
TI  - Demographic characteristics, care, and outcomes for children with oral clefts in
      three states using participants from the National Birth Defects Prevention Study.
AB  - OBJECTIVE: The primary objective of this study was to evaluate whether there were
      differences in the characteristics and outcomes of care for children with oral
      clefts (OCs) among population-based samples in three states. DESIGN: Data on the
      health status and on speech and esthetic outcomes were collected using structured
      telephone interviews conducted during 2005-2006 with mothers of children with OCs
      aged 2 to 7 in Arkansas, Iowa, and New York. PARTICIPANTS: Mothers of children
      born with nonsyndromic OCs on or after January 1, 1998, and on or before December
      31, 2003, in Arkansas, Iowa, or New York. Subjects were identified through their
      participation in the ongoing National Birth Defects Prevention Study. MAIN
      OUTCOME MEASURES: Demographic characteristics, rating of cleft care, severity of
      condition, health status, esthetic outcomes, and speech problems were evaluated
      by state of residence. RESULTS: Children with OCs from Arkansas were from lower
      income families, and their parents were less likely to be married. Children with
      OCs from Arkansas were more likely to have special health care needs and to
      require mental health care. Few differences were found across states in type of
      cleft, severity of cleft, or outcomes of cleft care. CONCLUSIONS: Combining
      results from population-based samples across multiple studies increases the
      variability of sample characteristics. Including multiple states can be an
      efficient way to learn more about the outcomes of medical care for less common
      conditions such as oral cleft.

PMID- 19860493
TI  - Rotation-transposition correction of nasal deformity in Tessier number 1 and 2
      clefts.
AB  - OBJECTIVE: To formulate a standardized procedure for repair of the nasal
      component of Tessier number 1 and 2 clefts. PATIENTS AND METHODS: The procedure
      was performed from 1998 to 2007 in 13 patients with congenital nasal clefts of
      different degrees of expression corresponding to Tessier 1 and 2. The patients'
      ages ranged from 3 months to 28 years. There were 10 male and three female
      patients. In the absence of any standard published technique for these rare
      defects, we devised our own method, which we find uniformly applicable to all
      such cases. We use a composite muco-chondro-cutaneous lateral alar flap to
      recreate the alar rim. The resulting defect on the lateral nasal wall is then
      covered with a transposition flap from the dorsum. An alar rim z-plasty was added
      in cases where notching was evident. RESULTS: In all cases, no problem of flap
      viability was encountered and all healed well with minimal scarring. The
      postoperative results were satisfactory and have remained stable over an average
      6-month follow-up period. CONCLUSIONS: We recommend this technique to be used for
      the correction of nasal deformity associated with Tessier clefts number 1 and 2.
      We feel that this technique is relatively simple and easily reproducible.

PMID- 19860495
TI  - Infant orthopedics and facial growth in complete unilateral cleft lip and palate
      until six years of age (Dutchcleft).
AB  - OBJECTIVE: To evaluate longitudinally the effect of infant orthopedics (IO) on
      dentofacial cephalometric variables in unilateral cleft lip and palate (UCLP)
      patients from 4 to 6 years of age. DESIGN: Prospective two-arm randomized
      controlled clinical trial in three cleft palate centers in The Netherlands
      (Dutchcleft trial). PATIENTS: Fifty-four children with complete UCLP.
      INTERVENTIONS: Patients were divided randomly into two groups. Half of the
      patients (IO+) had IO until surgical closure of the soft palate at the age of +/
      52 weeks; the other half (IO-) received no intervention. MEAN OUTCOME MEASURES:
      Cephalometric values representing soft tissue, hard tissue, and dental
      structures, measured on lateral headfilms made at 4 and 6 years of age. RESULTS:
      In the IO+ group, 21 patients were analyzed; in the IO- group, 20 patients were
      analyzed at age 4 and 22 at age 6. No differences were found between IO+ and IO-,
      except for two measurements: The interincisal angle was larger and the
      mentolabial angle was smaller in the IO+ group. CONCLUSIONS: For infants with
      UCLP whose surgical management included soft palate repair at 12 months and
      delayed hard palate closure, cephalometric outcomes at ages 4 and 6 provide no
      indication for the type of IO used in this study.

PMID- 19860496
TI  - Prenatal ultrasound diagnosis in 51 cases of holoprosencephaly: craniofacial
      anatomy, associated malformations, and genetics.
AB  - OBJECTIVE: To analyze the prenatal ultrasound findings of the craniofacial and
      extracephalic anatomy, the postnatal pathological findings, and the genetic
      anomalies in 51 cases of holoprosencephaly (HPE). MATERIALS AND METHODS: Between
      1990 and 2005, a collective of 51 fetuses with tentative ultrasound diagnosis of
      HPE was recruited at two tertiary referral centers for prenatal ultrasound
      diagnostics via the Pia Fetal Database (GEMedical Systems, Webling, Germany).
      Cephalic as well as extracephalic anomalies were investigated, and all cases were
      subdivided into the subgroups lobar, a lobar, and semilobar HPE. In addition to
      the ultrasound investigation, 45 fetuses were analyzed for genetic anomalies and
      21 fetuses underwent an autopsy. RESULTS: The average age at diagnosis was 21.9
      weeks of gestation. There was a greater number of female fetuses, with an overall
      ratio of 2.67:1. In 61% of all cases, there was a reduction of growth in
      comparison with healthy fetuses of the same age. Within the second trimenon, the
      cephalic anomalies became evident when investigating the diameter of the fetal
      head (second trimenon: 71%below the fifth percentile; third trimenon: 92% below
      the fifth percentile). In 82%of the cases, extracephalic anomalies were diagnosed
      additionally. In 63%, the diagnosis of holoprosencephaly led to a termination of
      pregnancy. Ten percent of the fetuses were born alive. In 81% of the cases, the
      diagnosis of HPE was confirmed postnatally. The remaining 19% showed other severe
      cephalic and extracephalic anomalies. Chromosomal anomalies were detected in 79%
      of the fetuses, most frequently trisomy 13 (59%). DISCUSSION: Because of recent
      advances in the development and improvement of high-resolution ultrasound, early
      diagnosis of congenital anomalies such as HPE is now possible. In this study,
      which represents the largest collection of prenatally diagnosed HPE reported in
      the literature to date, the average age at diagnosis was earlier than in other
      studies. The ultrasound devices of today provide excellent images of the fetus
      that allow an exact diagnosis of craniomaxillofacial anomalies as well as
      extracephalic anomalies. Apart from a very few cases, the diagnosis of HPE is
      incompatible with life.

PMID- 19860497
TI  - Dermatoglyphic analysis in parents with nonfamilial bilateral cleft lip and
      palate children.
AB  - OBJECTIVES: To test the hypothesis that unaffected parents with nonsyndromic
      bilateral cleft lip and palate children possess greater levels of dermatoglyphic
      asymmetry than the normal population and to test for the difference in the
      distribution of pattern types. DESIGN: Case-control study. SETTING: Mashhad
      University of Medical Sciences, Mashhad, Iran. PARTICIPANTS: Forty-five
      unaffected parents (45 men and 45 women) of children with nonfamilial bilateral
      cleft lip and palate anomaly were enlisted. A control group of 45 unaffected
      parents with at least two unaffected children and no prior family history of
      clefting were also simultaneously selected. MAIN OUTCOME MEASURES: Palm prints
      and fingerprints were taken from each participant, and total ridge counts, atd
      angles, and pattern types were determined. For each of the three dermatoglyphic
      measures, asymmetry scores between right and left hands were defined, and then
      asymmetry scores of unaffected parents and pattern types were compared
      statistically with the controls, using Mann-Whitney and chi-square tests.
      RESULTS: In contrast to total ridge count asymmetry, the asymmetry of at dangles
      in unaffected parents and the asymmetry of patterns (in unaffected mothers) were
      significantly higher in comparison with the controls. Furthermore,unaffected
      fathers had significantly more arches than the controls, but there were no
      significant differences in dermatoglyphic patterns of unaffected mothers and the
      controls. CONCLUSION: The findings suggest that an increase in the asymmetry of
      at dangles and pattern types in parents of sporadically affected children may
      reflect more the genetic base of this congenital malformation.

PMID- 19860498
TI  - Pediatric rhabdomyosarcoma in an oronasal fistula in a repaired cleft palate: a
      case report.
AB  - Rhabdomyosarcoma is a rare soft tissue tumor that was found incidentally in a
      repaired cleft palate oronasal fistula of a 3-year-old boy. This situation has
      yet to be reported in the literature. During this fistula repair, a small piece
      of tissue was sent for routine pathology, which showed embryonal
      rhabdomyosarcoma. A literature review as well as diagnostic and treatment
      algorithms are discussed concerning management of this rare malignancy. Also,
      routine pathology should be reviewed carefully because unsuspected tissues may
      have pathologic findings that dramatically affect patient diagnosis and
      management.

PMID- 19860499
TI  - Robin sequence: clearing nosologic confusion.
AB  - OBJECTIVE: To gather evidence surrounding the confusion in the classification of
      Robin sequence and inform those who have the power to make the changes in
      defining this symptom complex. METHOD: A questionnaire was sent to all
      participating cleft palate teams (N=204) of the American Cleft Palate
      Craniofacial Association. The questionnaire identified the precise, different
      characteristics for diagnosing Robin sequence and evaluated whether the
      difference between a retrognathia and micrognathia influenced the diagnosis
      process. We subsequently also investigated whether the cleft type (i.e., U-shaped
      versus V-shaped) had any influence in the decision-making process. A PubMed
      literature review of the 50 most recent manuscripts about Robin sequence was
      evaluated also. RESULTS: Seventy-three questionnaires were received. This 35%
      response rate revealed 14 different definitions of Robin sequence. A PubMed
      literature review of 50 consecutive manuscripts revealed 15 different
      descriptions. CONCLUSION: This study confirms that nosologic confusion is
      widespread with regard to defining Robin sequence. This has implications for
      evaluating Robin sequence, giving advice about the prognosis and genetic
      counseling, and refining treatment options.

PMID- 19860500
TI  - Early two-stage palatoplasty using modified Furlow's veloplasty.
AB  - OBJECTIVE: To achieve sufficient velopharyngeal function and maxillary growth for
      patients with unilateral cleft lip and palate (UCLP), the authors have designed a
      new treatment protocol for palate closure involving early two-stage palatoplasty
      with modified Furlow veloplasty. Details of the surgical protocol and the
      outcomes of the dental occlusion of patients at 4 years of age are presented.
      DESIGN AND SETTING: This was an institutional retrospective study. PATIENTS:
      Seventy-two UCLP patients were divided into two groups based on their treatment
      protocols: patients treated using the early two-stage palatoplasty protocol (ETS
      group; n = 30) and patients treated using Wardill-Kilner pushback palatoplasty
      performed at 1 year of age (PB group; n = 42). INTERVENTIONS: The features of the
      ETS protocol are as follows: The soft palate is repaired at 12 months of age
      using a modified Furlow technique. The residual cleft in the hard palate is
      closed at 18 months of age.Lip repair is carried out at 3 months of age with a
      modified Millard technique for all subjects. RESULTS: The ETS group showed a
      significantly better occlusal condition than the PB group.The incidence of normal
      occlusion at the non-cleft side central incisor was 7.1% in the PB group;
      whereas, it was 66.7% in the ETS group. CONCLUSION: The results indicate that the
      early two-stage protocol is advantageous for UCLP children in attaining better
      dental occlusion at 4 years of age.

PMID- 19860501
TI  - Dental evaluation of Kabuki syndrome patients.
AB  - Kabuki syndrome is a genetic disorder of unknown etiology characterized by mental
      retardation, growth deficiency, and peculiar face (i.e., long palpebral fissures,
      eversion of the lateral third of the lower eyelids, prominent ears, and broad and
      depressed nasal tip). Oral manifestations commonly observed in Kabuki syndrome
      may comprise cleft lip/palate, bifid tongue and uvula, malocclusion, and dental
      abnormalities. We evaluated the dental findings of eight patients with Kabuki
      syndrome. One presented cleft palate; three presented caries; and seven had
      missing teeth, with the upper lateral incisors and inferior central incisors
      being the most commonly absent. All missing teeth were permanent, and there was
      no alteration of dental chronology or morphology. Because most patients had mixed
      dentition, the presence or absence of primary teeth was assessed through the
      parents' reports. One patient presented an absent upper canine, which had not
      been reported previously in the literature. Dental findings may be helpful for
      clinical diagnosis, or they may be an additional finding to substantiate the
      diagnosis of Kabuki syndrome in children with mild phenotype.

PMID- 19860502
TI  - Bone regeneration and periosteoplasty: a 250-year-long history.
AB  - BACKGROUND: Since antiquity, many attempts have been carried out and a number of
      theories proposed to explain the process that leads to bone regeneration. Through
      manifold experiments, several authors tried to understand and subsequently to
      control the physiological events that enable bone healing. Between the 18th and
      19th centuries something changed. Although the scientific world was initially
      skeptical, a new idea emerged in the field of bone surgery. It principally
      concerned the necessity to perform amputations and resections leaving intact the
      periosteum to obtain new bone formation. MATERIALS AND METHODS: With this article
      we emphasize the contribution of many authors in the development of knowledge
      about the osteogenic properties of the periosteum. In particular we focus on the
      experiences of unknown Italian authors Michele Troja and Bernardino Larghi,
      consider well-recognized scientific personalities such as Leopold Ollier and
      Bernhard von Langenbeck, and reach a milestone of plastic surgery with Tord Skoog
      and his description of periosteoplasty. CONCLUSION: Various surgical approaches
      have been proposed to provide optimal care for patients with cleft lip and palate
      disorders. Among several treatment options, periosteoplasty is one of the choices
      to correct maxillary clefts. Highlighting difficulties and successes of many
      authors in demonstrating osteogenic properties of periosteum, this paper
      describes how periosteoplasty performed in maxillary cleft restoration
      capitalizes on what has been discovered during a 250-year-long history.

PMID- 19860503
TI  - Longitudinal study of growth of children with unilateral cleft-lip palate from
      birth to two years of age.
AB  - OBJECTIVE: To study the growth of children with complete unilateral cleft lip and
      palate (UCLP) from birth to 2 years of age and to construct specific UCLP growth
      curves. DESIGN: Physical growth was a secondary outcome measure of a National
      Institutes of Health-sponsored longitudinal, prospective clinical trial involving
      the University of Florida (United States) and the University of Sao Paulo
      (Brazil). PATIENTS: Six hundred twenty-seven children with UCLP, nonsyndromic,
      both genders. METHODS: Length, weight, and head circumference were prospectively
      measured for a group of children enrolled in a clinical trial. Median growth
      curves for the three parameters (length, weight, head circumference) were
      performed and compared with the median for the National Center for Health
      Statistics (NCHS) curves. The median values for length, weight, and head
      circumference at birth and 6, 12, 18, and 24 months of age were plotted against
      NCHS median values and statistically compared at birth and 24 months. SETTING:
      Hospital de Reabilitacao de Anomalias Craniofaciais, Universidade de Sao Paulo,
      Bauru, Brazil (HRAC-USP). RESULTS: At birth, children of both genders with UCLP
      presented with smaller body dimensions in relation to NCHS median values, but the
      results suggest a catch-up growth for length, weight, and head circumference for
      girls and for weight (to some degree) and head circumference for boys.
      CONCLUSIONS: Weight was the most compromised parameter for both genders, followed
      by length and then head circumference. There was no evidence of short stature.
      This study established growth curves for children with UCLP.

PMID- 19860504
TI  - Sagittal maxillary growth in patients with unoperated isolated cleft palate.
AB  - OBJECTIVE: To examine the sagittal maxillary growth during mixed and permanent
      dentition in patients with unoperated isolated cleft palate. PATIENTS: A total of
      41 patients with nonsyndromic unoperated isolated cleft palate, 16 with mixed
      dentition and 25 with permanent dentition. MAIN OUTCOME MEASURES: Cephalograms
      were analyzed to compare these patients with those with isolated cleft palate who
      had been repaired operatively as well with normal individuals. RESULTS: The
      unoperated patients in mixed dentition showed reduced anterior-posterior length
      of the maxilla. In adults with unoperated isolated cleft palate with permanent
      dentition, the measurements showed maxillary retrusion as well as reduction in
      the anterior-posterior maxillary length. CONCLUSION: Sagittal growth of the
      maxilla appears to be inhibited in patients with unoperated isolated cleft
      palate, which became more severe with age.

PMID- 19860505
TI  - Secondary alveolar bone grafting: outcomes, revisions, and new applications.
AB  - INTRODUCTION: Cleft lip and palate deformities are one of the most common birth
      defects. The alveolar cleft requires bony repair to allow proper eruption of
      dentition. The purpose of this study is to evaluate success in the repair of
      alveolar clefts and examine whether the addition of allogenic materials improves
      outcomes. MATERIALS AND METHODS: One hundred three patients with cleft lip and
      palate were identified retrospectively after institutional review board approval
      was obtained. The authors reviewed their medical records, surgical complication
      rate, need for revision surgery, and whether allogenic materials were used. The
      data were then compared using analysis of variance. RESULTS: The average patient
      age was 16.6 years (range, 7 to 25 years). There were 59% unilateral clefts and
      41% bilateral clefts identified. The average age at palate repair was 17.5
      months. The average age at alveolar bone grafting (ABG) was 8.9 years (range, 5
      to 15 years). Allogenic material was used in 22 primary ABGs and 10 revision
      ABGs. The revision rate of unilateral ABGs was 18%, which was statistically
      different from the 32% revision rate of bilateral ABGs. The use of allogenic
      material during ABG repair did not affect the revision rate. CONCLUSION:
      Secondary alveolar bone grafting is necessary for complete rehabilitation of the
      cleft alveolus. The patients undergoing ABG had an overall 23% revision rate, 18%
      for unilateral and 32% for bilateral clefts. The use of allogenic materials
      during ABG did not show a statistical benefit in this study, but future review
      including more patients may be useful.

PMID- 19860506
TI  - Craniofacial morphology in children of mothers with the m.3243A>G mutation in
      mitochondrial DNA.
AB  - OBJECTIVE: To describe craniofacial morphology in children from families with the
      mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS)
      syndrome. DESIGN: Transversal prospective case-control study from a tertiary
      center. SUBJECTS: Nine children (five girls, four boys; aged 7.5 to 15.3 years)
      of mothers with m.3243A>G mutation in mitochondrial DNA and 36 age- and sex
      matched healthy children as controls. METHODS: Seventy-three cephalometric
      variables representing craniofacial and dental features were analyzed in lateral
      radiographs. The statistical dependence caused by intrafamilial correlation was
      taken into account by using a two-level analysis of variance model that was
      fitted to the data using SAS procedure MIXED. RESULTS: The frontal bone was
      thicker and the frontal sinus, mandibular symphysis width, and lower posterior
      face height were larger in the subjects than in the controls. Upper incisors were
      more labially inclined, and the interincisal angle was smaller in subjects than
      in the control children. CONCLUSIONS: Differences were found in craniofacial
      structures between the children of mothers with m.3243A>G and unaffected
      children. Differences in the upper incisor inclination, mandibular symphysis
      width, and lower posterior face height suggest an altered mandibular growth
      pattern in the subjects. In addition, the children had cranial aberrations such
      as larger frontal sinuses and the thicker frontal bone.

PMID- 19860507
TI  - Filipino explanatory models of cleft lip with or without cleft palate.
AB  - OBJECTIVE: To describe beliefs about the cause, prevention, and treatment of
      cleft lip with or without cleft palate (CL+/-P) among working class people and
      health care workers in the Philippines. DESIGN AND SETTING: The study was a
      focused ethnography and took place in the province of Negros Occidental,
      Philippines. PARTICIPANTS: Using a stratified purposeful recruitment strategy, 80
      individuals were selected for study. They were categorized into three groups:
      those having a CL+/-P or a child with a CL+/-P, those who neither had a CL+/-P
      nor child with CL+/-P, and health care workers. METHODS: Kleinman's explanatory
      models of illness theory were used to elicit Filipino explanations for CL+/-P.
      Data were collected through guided individual and group informant interviews and
      analyzed through content analysis. RESULTS: Filipinos reported that inheritance,
      falls, cravings, environmental factors, and God's will were causes for CL+/-P.
      Beliefs about prevention of CL+/-P included limiting the number of children,
      being careful not to fall, and avoiding environmental factors. It was found that
      general causal explanations for CL+/-P were not always congruent with personal
      causal explanations, and general/personal causal explanations for CL+/-P were not
      always congruent with prevention explanations. CONCLUSION: By eliciting patients'
      explanations for CL+/-P and comparing these with their own, clinicians can find
      commonalities between divergent explanations and use these as a starting point
      from which to improve health outcomes. Findings from this study will be used to
      guide the design of health campaigns regarding CL+/-P in the Philippines.

PMID- 19860508
TI  - Combined use of infraorbital and external nasal nerve blocks for effective
      perioperative pain control during and after cleft lip repair.
AB  - Perioperative analgesia in patients undergoing cleft lip and palate repair is
      complicated by the risk of postoperative airway obstruction. We describe a
      technique of combined infraorbital and external nasal nerve blocks to reduce the
      need for opioid analgesia. Using this technique, we have successfully performed
      cleft lip repair under local anesthesia alone, without general anesthesia or
      intravenous sedation, in adolescents and adults. In children, this technique can
      reduce the need for postoperative opioids. We describe this novel analgesic
      approach to decrease opioid requirements and minimize perioperative risk.

PMID- 19860509
TI  - Timeliness of primary cleft lip/palate surgery.
AB  - OBJECTIVE: To examine the timeliness of primary cleft surgery, mean age at which
      surgery occurred, and factors associated with timely cleft surgery among children
      with orofacial clefts (OFCs). DESIGN: Retrospective study of children with OFC
      using North Carolina vital statistics, birth defects registry, and Medicaid
      files. PARTICIPANTS/PATIENTS: Medicaid-enrolled North Carolina resident children
      with OFC born from 1995 to 2002. MAIN OUTCOME MEASURES: Proportion of children
      who underwent primary cleft surgery within 18 months of life, mean age when
      surgery occurred, and factors associated with timely surgery. RESULTS: 406
      children with OFC were continuously enrolled in Medicaid during the first 2 years
      of life. Overall, 78.1% of children had surgery within 18 months. About 90% of
      children with cleft lip (CL), 58.0% of children with cleft palate (CP), and 89.6%
      of children with cleft lip and palate (CLP) received timely cleft surgery; the
      mean age at which surgery occurred was 5 months. Children whose mothers received
      maternity care coordination, received prenatal care at a local health department,
      or lived in the southeastern or northeastern region of the state were more likely
      to receive timely cleft surgery. CONCLUSION: Most children with OFC in North
      Carolina born during this time period received primary cleft surgery within 18
      months of life, but this varied by maternal demographics and other factors.

PMID- 19860510
TI  - Apples and oranges-midface hypoplasia and the Le Fort I osteotomy in cleft lip
      and palate patients: a classification scheme and treatment protocol.
AB  - OBJECTIVE: To present a classification and treatment protocol for cleft lip and
      palate patients with midface hypoplasia. DESIGN: Retrospective case series.
      SETTING: Craniofacial center. PATIENTS: The study included 133 patients with
      cleft lip and palate and maxillary hypoplasia treated with Le Fort I osteotomy
      between January 2000 and July 2006. INTERVENTIONS: Modified Le Fort I osteotomy.
      Patients were divided into three groups based on the number of free-standing bony
      maxillary segments, and treatment was tailored to their deformity. MAIN OUTCOME
      MEASURES: Complications and long-term relapse rates. RESULTS: The 133 patients
      underwent 142 operations with mean follow-up of 27 months. Mean horizontal
      advancement was 7.1 +/- 1.9 mm, 6.5 +/- 1.3 mm, 6.4 +/- 1.6 mm, and 6.5 +/- 1.3
      mm for groups I, II, IIIA, and IIIB, respectively. Complications consisted of
      nine bony relapses, three hematomas, and two transitory neurosensory losses.
      Analysis of variance using number of maxillary pieces as the independent variable
      and millimeters of advancement as the dependent variable demonstrated no
      difference in the amounts that the groups were advanced (p = .23). Relapse rates
      for groups I, II, IIIA, and IIIB were 2/62 (3.2%), 5/53 (9.4%), 2/14 (14.3%), and
      0/4 (0.0%), respectively. Analysis of variance did not demonstrate a statistical
      difference in relapse rates based on number of maxillary pieces. CONCLUSIONS:
      Cleft lip and palate patients can be classified into three groups based on the
      number of maxillary segments. Our classification system defines the differences
      among this diverse group of patients and also facilitates unique treatment of
      each group.

PMID- 19860512
TI  - Secondary alveolar bone grafting (CLEFTSiS) 2000-2004.
AB  - OBJECTIVE: To determine whether alveolar bone graft outcomes improved with
      reorganization of Scottish cleft services following the Clinical Services
      Advisory Group United Kingdom finding of 58% success and to determine the
      accuracy of results from CLEFTSiS (national managed clinical network for Scottish
      cleft services) annual audits. DESIGN: Retrospective random analysis of
      electronic radiographs by two observers. SETTING: Surgical-orthodontic care
      provided through National Health Service. PATIENTS, PARTICIPANTS: Sixty-three of
      261 patients eligible for alveolar bone grafting by cleft type did not undergo
      surgery. Nine surgeons operated on 198 patients (2 regrafts). Radiographs were
      available for 115 subjects (one was excluded). INTERVENTIONS: A standard protocol
      involved presurgical maxillary expansion (where necessary) and bone harvesting
      from the iliac crest. MAIN OUTCOME MEASURE(S): The Kindelan Bone-Fill Index
      evaluated radiographic success with weighted kappa statistics for intraobserver
      and interobserver reproducibility. Two-sample t-tests were used to determine
      whether outcomes for ilateral and unilateral cleft lip and palate patients
      differed and to examine the effects of operator volume, presurgical expansion,
      and age at the time of grafting. RESULTS: Intraobserver (0.93 to 0.97) and
      interobserver (0.83 to 0.85) reproducibility were almost perfect. Grafts were
      successful in 76% of patients, while 23% were partial failures and 1% of cases
      were total failures. Patients who underwent presurgical expansion (n = 64) had
      statistically significantly better results (p = .046). However, there was no
      statistically significant effect for unilateral versus bilateral patients (p =
      .77), patients treated by the highest volume operator (p = .78), and patients
      under 11 years of age (p = .29). CONCLUSIONS: CLEFTSiS alveolar bone graft
      results between 2000 and 2004 were improved on the Clinical Services Advisory
      Group study and annual CLEFTSiS audits. Patients who underwent maxillary
      expansion prior to surgery were more successful.

PMID- 19860513
TI  - Quantitative measurement of symmetry from photographs following surgery for
      unilateral cleft lip and palate.
AB  - A computer-based program is presented to be used with digitized frontal and basal
      photographs. SymNose enables the user to quantify asymmetry of the front view of
      the lip and nose and of the nose from the base view, using the area of mismatch
      of one side reflected over the other. There is a facility to transfer results to
      a spreadsheet. The program is simple and quick to use and runs on Apple Macintosh
      OSX 10.4 or later, power and Intel-based systems. The outline of a feature can be
      drawn using the mouse or digitizing pad. The program, together with Help files,
      is available from the authors.

PMID- 19860516
TI  - Association between cleft size and crossbite in children with cleft palate and
      unilateral cleft lip and palate.
AB  - OBJECTIVE: To investigate the association between cleft size in infancy and
      crossbite at 5 years of age in children with cleft palate (CP) and unilateral
      cleft lip and palate (UCLP). DESIGN: Retrospective study. SETTING: University
      Hospital, Uppsala, Sweden. PATIENTS: Dental study models of 80 consecutive
      children, 51 children with CP and 29 children with UCLP, born between 1990 and
      1999 were analyzed. INTERVENTIONS: Lip repair at 3 to 4 months in UCLP children.
      Primary soft palate repair at 6 to 10 months and secondary hard palate closure at
      25 to 26 months of age. MAIN OUTCOME MEASURES: Maxillary arch dimensions and
      cleft size were measured on infancy dental casts. At follow-up at 5 years,
      crossbite scores were registered on dental study models. RESULTS: The cleft
      dimensions in infancy showed large interindividual variation. Mean posterior
      cleft width was larger in UCLP children than in children with CP. The UCLP group
      also had significantly more crossbite at 5 years than the CP group. No
      significant association was noted between initial cleft size and crossbite scores
      at 5 years in the CP group. For the UCLP group, larger cleft widths at the level
      of the cuspid points were significantly associated with less anterior and
      posterior crossbite. CONCLUSIONS: The findings support the hypothesis that cleft
      size in infancy affects early outcome with respect to crossbite in children with
      UCLP, but not in children with CP.

PMID- 19860517
TI  - Psychosocial adjustment in children and adolescents with a craniofacial anomaly:
      diagnosis-specific patterns.
AB  - OBJECTIVE: To obtain descriptive information about diagnosis-specific patterns of
      psychosocial adjustment for children and adolescents with craniofacial anomalies.
      DESIGN: Chart review of medical records was used to obtain psychosocial
      checklists. Scores were compared with published norms to evaluate elevated risk
      of problems, separately for six diagnostic groups. SETTING: Plastic surgery
      department in urban university medical center. PARTICIPANTS: As part of routine
      ongoing care, 408 caregivers completed checklists assessing psychosocial
      adjustment of children aged 2 to 18 years with diagnosis of cleft lip and palate,
      cleft lip only, cleft palate only, craniosynostosis, hemifacial microsomia, and
      hemangioma. MAIN OUTCOME MEASURE: Child Behavior Checklist ( Achenbach, 1991 ,
      1992 ). RESULTS: The craniosynostosis group showed elevated rates (beyond norms)
      of social, academic, and attention problems. The cleft lip and palate group
      showed elevations in social problems and deficits in social, academic, and
      activities competencies. The other diagnostic groups had few areas of elevated
      problems and had reduced risk in some areas. CONCLUSION: Specific patterns of
      strengths and weaknesses in psychosocial adjustment may vary by craniofacial
      anomaly diagnosis. Replication of these findings, with extension to other
      craniofacial anomaly diagnoses, is warranted.

PMID- 19860518
TI  - Photometric evaluation of bilateral cleft lip and palate patients after primary
      columella lengthening.
AB  - OBJECTIVE: To evaluate the results in terms of nasal esthetics of children with
      bilateral cleft lip and palate, operated with the Cutting primary columella
      lengthening technique, associated with Grayson orthopedic nasoalveolar molding,
      and to compare them with the nasal aspects of children with bilateral cleft lip
      and palate operated with a traditional approach and to an age-matched sample of
      normal Caucasian children. DESIGN: Normalized photogrammetry. SETTING: Regional
      Center for CLP, Department of Maxillo-Facial Surgery, San Paolo Hospital, Milan.
      PATIENTS: Three groups of patients 5 years of age. Cutting group: 18 patients
      treated with the Grayson-Cutting technique. Delaire group: 18 patients treated
      with the traditional Delaire technique. Normal children: 40 normal preschool
      children. RESULTS: With the Cutting-Grayson technique, the columella length,
      nasal tip angle, and protrusion are greatly improved compared with the previous
      protocol and are close to normal. On the other hand, the nasolabial angle and
      interalar distances are still excessively wide in both samples. CONCLUSIONS:
      Although this is not a long-term study, at this time none of the patients
      operated with this technique have needed secondary columella lengthening. On the
      other hand, although certainly improved, the nasal anatomy obtained is far from
      normal.

PMID- 19860519
TI  - Parental perspectives of children born with cleft lip and/or palate: a
      qualitative assessment of suggestions for healthcare improvements and
      interventions.
AB  - OBJECTIVE: To assess parental perspectives on effective interventions and to
      summarize parents' suggestions for health care professionals to improve the care
      provided to their children born with cleft lip and/or palate. DESIGN: Qualitative
      interviews. SETTING: Comprehensive craniofacial center at a Midwest pediatric
      hospital. PARTICIPANTS: Seventeen parents of children under the age of 1 who were
      born with CL/P. RESULTS: Interventions that parents identified as effective
      included repetition of information, showing pictures of other children (before
      and after surgery), and anticipatory guidance about surgeries and their child's
      development. Despite the high level of satisfaction, parents expressed a desire
      for health care professionals to use more written and visual information, to have
      more contact with other parents of children born with clefts, and for health care
      professionals outside the Craniofacial Center to be more knowledgeable about
      CL/P. CONCLUSIONS: Although parents of children with CL/P were for the most part
      satisfied with their children's care, the parents who were interviewed for this
      study suggested attainable changes that may result in more constructive and
      positive involvement of parents as integral members of the craniofacial team.

PMID- 19860520
TI  - A case of ring chromosome 18 syndrome treated with a combined orthodontic
      prosthodontic approach.
AB  - OBJECTIVE: The aim of this study was to report the case of a Japanese subject
      with ring chromosome 18 syndrome. A cephalometric analysis was performed, and the
      treatment procedure is described. DESIGN: Lateral and posteroanterior
      cephalograms were compared with Japanese norms. Dental anomalies were evaluated
      by a model analysis. The outcome of orthodontic-prosthodontic treatment was
      evaluated by comparing cephalograms during the course of treatment. RESULTS: The
      cephalometric analysis showed a reduction in the cranial base length and cranial
      width, midfacial depth, and height and width. Comparison of lateral cephalograms
      at age 16 years 6 months and 22 years 4 months showed late growth of the
      mandible. The model analysis showed that all of the teeth, except for the
      mandibular canine, were small. CONCLUSIONS: Characteristic craniofacial and
      dental anomalies were clarified. Successful oral rehabilitation was achieved by
      combined orthodontic-prosthodontic treatment.

PMID- 19860522
TI  - Clinical features of the microform cleft lip and the ultrastructural
      characteristics of the orbicularis oris muscle.
AB  - OBJECTIVE: To clarify the clinical features of the microform cleft lip and to
      establish the ultrastructural characteristics of the orbicularis muscle. DESIGN:
      Clinical observations of the characteristic deformities and associated anomalies
      were made. Muscle biopsies were harvested for histologic and ultrastructural
      analyses. PATIENTS: Seventy-one consecutive patients with microform cleft lip
      were included in the study. Muscle biopsies were investigated in 11 patients
      among them. RESULTS: Nasal deformity, a ridge or a groove from the vermilion to
      the nostril sill, and interruption of the "white roll" were present in all
      patients. Lack of a philtral column and a free border notch was observed in over
      97% of patients. The orbicularis muscle demonstrated hypoplastic myofibers with
      nonneurogenic atrophy and focal accumulation of subsarcolemmal mitochondria.
      CONCLUSION: The typical gross morphology of the microform cleft lip is a surface
      manifestation of muscular defect, and the disruption of the muscle further
      extends down to the ultrastructural level. The clinical features, taken together
      with the ultrastructural defects of the musculature, might help with a more
      precise delineation of the microform cleft lip, and provide better understanding
      of cleft lip in general.

PMID- 19860523
TI  - Median facial cleft dysmorphism in three siblings: case report and review of the
      literature.

PMID- 19860525
TI  - Hypodontia in Beare-Stevenson syndrome: an example of dental anomalies in FGFR
      related craniosynostosis syndromes.
AB  - The authors report a new case of Beare-Stevenson syndrome (BSS) characterized by
      cutis gyrata, craniosynostosis, acanthosis nigricans, ear defects, a prominent
      umbilical stump, and midface hypoplasia. The patient had dental findings of natal
      teeth and hypodontia of the primary and permanent teeth. This is the second
      patient with BSS syndrome to be reported with hypodontia and natal teeth; the
      first patient was described by Beare in 1969. The authors review the current
      literature to investigate the relationship between dental anomalies and
      fibroblast growth factor receptor-related mutations in BSS and other
      craniosynostosis syndromes such as Apert, Crouzon, and Pfeiffer.

PMID- 19860526
TI  - Prenatal diagnosis of craniomaxillofacial malformations: a characterization of
      phenotypes in trisomies 13, 18, and 21 by ultrasound and pathology.
AB  - OBJECTIVE: To determine the relationship between trisomies 13, 18, and 21 and
      craniofacial malformations detected by prenatal sonography. DESIGN: During a 29
      year period (1976 through 2004), prenatal sonographic findings of 69 fetuses with
      trisomy 13; 171 fetuses with trisomy 18; 302 fetuses with trisomy 21; and 17
      fetuses with other trisomies were evaluated retrospectively, after fetal
      karyotype identification. Sonographic findings were compared with autopsy results
      in 209 patients (trisomy 13, n=39; trisomy 18, n=64; and trisomy 21, n=106).
      RESULTS: For trisomy 13, cleft deformities were detected prenatally in 65.2%, and
      of the 39 cases with pathological information, 76.9% were found to have a cleft
      deformity. Ocular and orbital abnormalities were found in 28%. Malformations of
      the jaws and abnormal profiles were more frequently diagnosed postnatally than
      prenatally. For trisomy 18, abnormal profiles (41.5%) and ear abnormalities
      (5.3%) were the most noticeable ultrasound markers, next to abnormalities of the
      neurocranium (36.8%) and cranial bone configuration (21.6%). Dysmorphisms of the
      eye, ear, or nose were detected more frequently in autopsy cases. For trisomy 21,
      ultrasound showed an aberrant shape of the skull in 14.2% of fetuses. In general,
      the ocular-orbital and nasal abnormalities in fetuses with trisomy 18 or 21 were
      more evident in pathological examination than in prenatal ultrasound imaging.
      CONCLUSIONS: Facial anomalies are common in the major trisomies, and their
      prenatal sonographic identification should be improved. The above-mentioned
      facial anomalies provide sufficient reason to consider performing cytogenic
      evaluation.

PMID- 19860527
TI  - Effects of velopharyngeal dysfunction on middle ear of repaired cleft palate
      patients.
AB  - OBJECTIVE: Cleft palates are strongly associated with the development of otitis
      media due to the anatomic and functional defect of the soft palate musculature
      and the associated alterations of velopharyngeal muscle insertion on tubal
      cartilage, or even intrinsic alterations of the cartilage, which affects
      eustachian tube function. This study will assess velopharyngeal muscle adequacy
      after palatoplasty through videonasoendoscopy and verify if there is a
      correlation with otologic status. DESIGN: Transversal study. SETTING:
      Otorhinolaryngology and cleft palate outpatient service of the Hospital de
      Clinicas de Porto Alegre (HCPA), Porto Alegre, Brazil. PATIENTS: Seventy-three
      patients with cleft palate or cleft lip and palate between the ages of 6 and 12
      years who had already undergone palatoplasty. INTERVENTIONS: Videonasoendoscopy
      for evaluation of velopharyngeal function and videotoscopy to assess middle ear
      status. MAIN OUTCOME MEASURES: Severity scale for videonasoendoscopic and
      videotoscopic findings. RESULTS: There was no significant correlation between the
      videonasoendoscopic and the videotoscopic scores in the population studied.
      DISCUSSION AND CONCLUSIONS: Intrinsic defects of the eustachian tube cartilage
      and of the insertion of the velopharyngeal muscles seem to contribute to the
      evolution of otitis media in patients with cleft palate, in addition to the
      actual defect of the soft palate. There was no correlation between the severity
      of the otoscopic findings and the degree of velopharyngeal dysfunction.

PMID- 19860528
TI  - Dental arch relationship in children with complete unilateral cleft lip and
      palate following Warsaw (one-stage repair) and Oslo protocols.
AB  - OBJECTIVE: To compare the dental arch relationship following one-stage repair of
      unilateral cleft lip and palate (UCLP) in Warsaw with a matched sample of
      patients treated by the Oslo Cleft Team. MATERIAL: Study models of 61 children
      (mean age, 11.2; SD, 1.7) with a nonsyndromic complete UCLP consecutively treated
      with one-stage closure of the cleft at 9.2 months (range, 6.0 to 15.8 months; SD,
      2.0) by the Warsaw Cleft Team at the Institute of Mother and Child, Poland, were
      compared with a sample drawn from a consecutive series of patients with UCLP
      treated by the Oslo Cleft Team and matched for age, gender, and soft tissue band.
      METHODS: The study models were given random numbers to blind their origin. Four
      examiners rated the dental arch relationship using the GOSLON Yardstick. The
      strength of agreement of rating was assessed with weighted Kappa statistics. An
      independent t-test was carried out to compare the GOSLON scores between Warsaw
      and Oslo samples, and Fisher's exact tests were performed to evaluate the
      difference of distribution of the GOSLON scores. RESULTS: The intrarater and
      interrater agreements were high (K > or = .800). No difference in dental arch
      relationship between Warsaw and Oslo groups was found (mean GOSLON score = 2.68
      and 2.65 for Warsaw and Oslo samples, respectively). The distribution of the
      GOSLON grades was similar in both groups. CONCLUSIONS: The dental arch
      relationship following one-stage repair (Warsaw protocol) was comparable with the
      outcome of the Oslo Cleft Team's protocol.

PMID- 19860529
TI  - The effects of hyperbaric oxygen on tooth movement into the regenerated area
      after distraction osteogenesis.
AB  - OBJECTIVE: To analyze the effect of hyperbaric oxygen on newly formed bone in
      distracted areas surrounding the root of a moving tooth by histological and
      radiological analysis. It was hypothesized that the application of hyperbaric
      oxygen to a tooth moving into the distracted area would accelerate ossification
      and vascularization of newly formed bone in the distracted space. DESIGN: Ten
      dogs were used. After creating a 10-mm-long bone defect, a bony segment was
      prepared and translocated into the defect area at a rate of 1 mm/d for 10 days.
      Following the distraction period, tooth movement was started and the dogs were
      divided into two groups. The HBO group received hyperbaric oxygen; whereas, the
      control group did not. At 150 days after tooth movement, the distracted area
      around the moving tooth was evaluated radiologically and histologically.
      Differences between groups were confirmed by a Mann-Whitney U test. RESULTS:
      Trabecular bone density and cortical and subcortical bone areas measured by
      peripheral quantitative computed tomography in the HBO group were significantly
      higher than those in the control group. Histological observations revealed
      regenerated bone and blood vessels formation in the tension site of the moving
      tooth in the HBO group. The regenerated bone structure measured by bone
      histomorphometry was larger and more active in bone formation in the HBO group
      than in the control group. CONCLUSIONS: Applying hyperbaric oxygen to tooth
      movement into a distracted area appears to accelerate ossification and
      vascularization of regenerated bone in the that area.

PMID- 19860531
TI  - A case of congenitally absent left internal carotid artery: vascular
      malformations in 22q11.2 deletion syndrome.
AB  - Our report is on a Hispanic boy for whom, shortly after birth, clinical suspicion
      of 22q11.2 deletion syndrome (22q11.2DS) was raised as a result of his
      characteristic features, including facial dysmorphisms and hypotonia. The
      22q11.2DS was confirmed by fluorescence in situ hybridization (FISH), noting a
      22q11.2 deletion. Further evaluation revealed complete congenital absence of the
      left internal carotid artery and focal pachygyria of the left hemisphere.
      Multiple cardiac and vascular anomalies have been previously described in 22q11
      deletion syndrome, but congenital absence of the internal carotid has not been
      previously reported in the literature. We present a clinical case report in
      detail of this unique 22q11.2 deletion syndrome associated finding.

PMID- 19860533
TI  - The experiences of dentists in the management planning of oral health services in
      Lesotho, Africa.
AB  - INTRODUCTION: Health sector reforms motivated by the need for efficiency,
      effectiveness and equity in the delivery of services have interested authorities
      in the planning competencies of managers, because planning sets the stage for the
      effective management of health systems. The huge public and private cost of oral
      health makes planning an important dimension for health authorities when
      considering the allocation of funds. Productivity in the oral health service
      sector is not often reported on, despite the cost involved in rendering oral
      health services. This study explores and describes the management planning
      experiences of oral health managers in the public sector in Lesotho, Africa,
      which consists of clinics in 10 districts serving hundreds of rural and remote
      mountainous communities. METHODS: The study used a qualitative research design.
      Of the purposive sample of 14 public sector dentists then available, seven
      dentists (2 female and 5 male) met the criteria for participation (> or = 1 year
      of experience in district oral health planning), and consented to and were
      available for participation. Data were collected by in-depth, one-on-one
      interviews with 6 participants, and textual data were collected from the seventh.
      Interviews were audiotaped and transcribed verbatim. Data were organised and
      analysed using the Tesch method, with themed topics coded and categorised by a
      researcher and an independent coder for analysis. RESULTS: One major theme
      emerged (the management planning of oral health services were experienced as
      inefficient) and four sub-themes: (1) the need to plan carefully to provide
      efficient clinical services; (2) constraints to promoting expansion of community
      based dental services; (3) a breakdown in communication hampered service
      delivery; and (4) internal and external stakeholder issues impacted strongly on
      management planning. CONCLUSION: The inefficiency (failure of the community to
      derive maximum curative, preventive and rehabilitative benefits from public
      expenditure on oral health in Lesotho), as described by participants, arose from
      factors that impair careful planning; constrained the expansion of community
      based oral health services; caused a breakdown in communication between dentists
      and their authorities leading to poor services delivery; and was impacted
      strongly by internal and external stakeholder issues.

PMID- 19860532
TI  - Spatial variation of haemosporidian parasite infection in African rainforest bird
      species.
AB  - Spatial heterogeneity influences the distribution, prevalence, and diversity of
      haemosporidian parasites. Previous studies have found complex patterns of
      prevalence with respect to habitat characteristics and parasite genotype, and
      their interactions, but there is little information regarding how parasitemia
      intensity and the prevalence of co-infections may vary in space. Here, using both
      molecular methods and microscopy, we report an analysis of the variation of
      parasitemia intensity and co-infections of avian haemosporidian parasites (
      Plasmodium and Haemoproteus species) in 2 common African birds species, the
      yellow-whiskered greenbul ( Andropadus latirostris ) and the olive sunbird (
      Cyanomitra olivacea ), at 3 sites with distinct habitat characteristics in Ghana.
      First, we found an interaction between the site and host species for the
      prevalence of Plasmodium spp. and Haemoproteus spp. For the olive sunbird, the
      prevalence of Plasmodium spp., as well as the number of individuals with co
      infections, varied significantly among the sites, but these measures remained
      constant for the yellow-whiskered greenbul. In addition, yellow-whiskered
      greenbuls infected with Haemoproteus spp. were found only at 1 site. Furthermore,
      for both bird species, the parasitemia intensity of Plasmodium spp. varied
      significantly among the 3 sites, but with opposing trends. These results suggest
      that spatial heterogeneity differently affects haemosporidian infection
      parameters in these vertebrate-hosts. Environmental conditions here can either
      favor or reduce parasite infection. We discuss the implications of these
      discrepancies for conservation and ecological studies of infectious diseases in
      natural populations.

PMID- 19860534
TI  - Self-ordered nanopore and nanotube platforms for drug delivery applications.
AB  - The application of nanotechnology to medicine termed as 'nanomedicine' is
      recognised as an emerging field with enormous potential for developing new
      therapeutic concepts. A range of nanoscale materials have been explored in the
      last few years for drug delivery to address the problems associated with
      conventional drug therapies such as limited drug solubility, poor
      biodistribution, lack of selectivity and unfavourable pharmacokinetics. Among
      them, nanoporous materials with ordered and controlled pore structures, high
      surface area and pore volume, attracted great attention, particularly for
      implantable drug delivery systems. This review presents the recent progress in
      this field focused on electrochemically engineered nanopores/nanotube materials
      such as nanoporous alumina and nanotubular titania. The basic concept of
      fabrication of these unique materials using a self-ordering process, description
      of their structural properties, biocompatibility and recent applications for
      therapeutic implants is presented.

PMID- 19860535
TI  - Electrodes for in vivo localised subcutaneous electropulsation and associated
      drug and nucleic acid delivery.
AB  - BACKGROUND: Drug and nucleic acids can be delivered in vivo by an injection of
      the product followed by the application of a train of electric pulses. OBJECTIVE:
      The success of the method is linked to the proper distribution of the electric
      field in the target tissue. This is under the control of the design of the
      electrodes. METHODS: The field distribution can be obtained by computer
      simulation mainly by using numerical methods and simplifying hypothesis. The
      conclusions are validated by comparing the computed current and its experimental
      values on phantoms. A good agreement is obtained. RESULTS/CONCLUSION: Targeting
      the delivery to the skin can be obtained by using an array of very short needle
      electrodes, by pinching the skin between two parallel plate electrodes, or by
      using contact wire electrodes.

PMID- 19860536
TI  - Safety evaluation of enoxaparin in currently approved indications.
AB  - BACKGROUND: Potential limitations of unfractionated heparin (UFH) have prompted a
      search for new antithrombin therapies in recent years. Enoxaparin has shown
      similar or improved efficacy when compared with UFH, but it has been associated
      with safety concerns of increased bleeding in patients with acute coronary
      syndromes in some studies. OBJECTIVE: This narrative review focuses on the safety
      and tolerability of enoxaparin in adult patients in the setting of currently
      approved indications. METHODS: Synthesis of evidence from recent trials,
      systematic reviews, meta-analyses, regulatory documents and clinical trials
      registries of manufacturers. CONCLUSION: Enoxaparin can be considered for
      prophylaxis and treatment of a wide range of thrombotic conditions as an
      alternative to UFH with a clinically modest increase in bleeding complications,
      without altering the risk-benefit profile of this compound. Selection of the
      appropriate dosage is strongly recommended. Special precautions should be taken
      in specific populations that are at higher risk of bleeding, such as patients
      with renal dysfunction and elderly patients, where dose adjustment is
      recommended.

PMID- 19860537
TI  - Update on emerging drugs for cancer cachexia.
AB  - Cancer cachexia is a complex syndrome that describes the progressive muscle
      wasting and weakness in many cancer patients. Muscle wasting reduces the ability
      of affected patients to perform the tasks of daily living and causes severe
      fatigue, leading to a reduction in quality of life. Cancer cachexia reduces
      patient response to anti-neoplastic treatments, increases the risk of
      postoperative complications and accounts for > 20% of cancer-related deaths. The
      pathogenesis of cancer cachexia is multifactorial and includes anorexia,
      inflammation, metabolic disturbances and enhanced muscle proteolysis, and each of
      these presents as a potential therapeutic target for ameliorating cancer
      cachexia. OBJECTIVE: This review provides an update on some of the emerging drugs
      for cancer cachexia. METHODS: This is a review of the current status of emerging
      therapies for cancer cachexia. RESULTS: An increasing number of studies are
      focused on the development of novel therapies for cancer cachexia. Initial
      studies concentrated on the treatment of anorexia, but now aim to attenuate
      inflammation or muscle proteolysis, or to use different drugs in combination so
      as to treat several aspects of cachexia simultaneously. CONCLUSIONS: There are
      several existing and emerging drugs with the potential to ameliorate cancer
      cachexia, but the most efficacious treatment will probably come from combined
      drug therapies.

PMID- 19860539
TI  - Don't diss integration: a comment on Ricklefs's disintegrating communities.
AB  - Ricklefs's recent call to investigate ecological processes at large scales helps
      focus ecologists' attention on an undoubtedly important topic. However, we
      believe that some of his accompanying arguments for the primacy of such work and,
      in particular, for the need to "disintegrate" the local community concept are
      flawed. We revisit Ricklefs's main tenets and demonstrate that research on local
      communities is a vital part of understanding processes and diversity across a
      range of spatial and temporal scales. The integration of research across spatial
      scales expands our horizons and understanding of ecology and evolution, and this
      should not be unnecessarily constrained to one extreme or the other.

PMID- 19860540
TI  - Vegetation, fire, and feedbacks: a disturbance-mediated model of savannas.
AB  - Savanna models that are based on recurrent disturbances such as fire result in
      nonequilibrium savannas, but these models rarely incorporate vegetation feedbacks
      on fire frequency or include more than two states (grasses and trees). We develop
      a disturbance model that includes vegetation-fire feedbacks, using a system of
      differential equations to represent three main components of savannas: grasses,
      fire-tolerant savanna trees, and fire-intolerant forest trees. We investigate the
      stability of savannas in the presence of positive feedbacks of fire frequency
      with (1) grasses, (2) savanna trees, and (3) grasses and savanna trees together
      while also allowing for negative feedbacks of forest trees on fire frequency. We
      find that positive feedbacks between fire frequency and savanna trees, alone or
      together with grasses, can stabilize savannas, blocking the conversion of
      savannas to forests. Negative feedbacks of forest trees on fire frequency shift
      the range of parameter space that supports savannas, but they do not generally
      alter our results. We propose that pyrogenic trees that modify characteristics of
      fire regimes are ecosystem engineers that facilitate the persistence of savannas,
      generating both threshold fire frequencies with rapid changes in community
      composition when these thresholds are crossed and hystereses with bistable
      community states.

PMID- 19860542
TI  - Production and characterization of polymer microspheres containing trace
      explosives using precision particle fabrication technology.
AB  - Well characterized test materials are essential for validating the performance of
      current trace explosive detection systems. These test materials must replicate
      trace explosive contamination in the form of small particles with characteristic
      diameters in the micrometer range. In this work, Precision Particle Fabrication
      was used to fabricate monodisperse polymer microspheres that contain high
      explosives. Three high explosives were successfully incorporated into the
      microspheres. Ion mobility spectrometry confirmed that the encapsulation
      efficiency was typically greater than 50%, with some suspected loss to the
      aqueous phase during production. This study demonstrates that, with this
      technique, polymer microspheres containing explosives can be produced with
      sufficient encapsulation, along with tightly controlled particle size
      distributions at high production rates. These microspheres have proven to be a
      valuable test material for trace explosive detectors because of their highly
      precise size, shape and explosive composition.

PMID- 19860541
TI  - The maintenance of genetic variation due to asymmetric gene flow in dendritic
      metapopulations.
AB  - Dendritic landscapes can have ecological properties that differ importantly from
      simpler spatial arrangements of habitats. Most dendritic landscapes are
      structured by elevation, and therefore, migration is likely to be directionally
      biased. While the population-genetic consequences of both dendritic landscape
      arrangements and asymmetric migration have begun to be studied, these processes
      have not been considered together. Simple conceptual models predict that if
      migration into branch (headwater) populations is limited, such populations can
      act as reservoirs for potentially unique alleles. As a consequence of the fact
      that dendritic landscapes have, by definition, more branches than internal
      habitat patches, this process may lead to the maintenance of higher overall
      genetic diversities in metapopulations inhabiting dendritic networks where
      migration is directionally biased. Here we begin to address the generality of
      these simple predictions using genetic models and a review of empirical
      literature. We show, for a range of demographic parameters, that dendritic
      systems with asymmetric migration can maintain levels of genetic variation that
      are very different, sometimes very elevated, compared with more classical models
      of geographical population structure. Furthermore, predicted patterns of genetic
      variation within metapopulations--that is, stepwise increases in genetic
      diversity at nodes--do occur in some empirical data.

PMID- 19860543
TI  - MYH9 related disease: a novel missense Ala95Asp mutation of the MYH9 gene.
AB  - MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by
      mutations in MYH9, the gene encoding the heavy chain of non-muscle myosin IIA.
      Patients present with congenital macrothrombocytopenia and inclusion bodies in
      neutrophils and might develop sensorineural deafness, presenile cataract, and/or
      progressive nephritis leading to end-stage renal failure. In a family with eight
      individuals suffering from macrothrombocytopenia and hearing impairment we
      identified a novel c.Ala95Asp mutation. Affecting the motor domain of the
      protein, the mutation is likely to be associated with a severe phenotype.
      Therefore, this family should be carefully monitored to follow-up the renal
      status even though the affected members do not seem to be at risk of early kidney
      disease.

PMID- 19860545
TI  - The measurement of analyte diffusion from hydrogel microcapsules in model aqueous
      environments.
AB  - Model flavor analytes with varying partition coefficients were successfully
      encapsulated in approximately 150 microm diameter hydrogel microcapsules
      containing medium chain triglycerides (MCT). Analyte diffusion from the
      microcapsules into water and dextrose solutions was measured using a UV-VIS
      spectrophotometer fitted with a fiber optic probe. The diffusion of acetophenone,
      considered a hydrophilic analyte, was reduced as the dextrose concentration was
      increased in the water environment. Diffusion comparison was noted as t(1/2)
      which is the measure of time when 50% of the analyte concentration is released
      from the microcapsules. The measured t(1/2) for acetophenone in distilled water
      was 0.40 min. The addition of 20% dextrose to distilled water increased the
      t(1/2) to 0.60 min while the 40% dextrose addition extended the t(1/2) to 1.4
      min. The same t(1/2) trends were also noted with methyl salicylate which is
      considered a hydrophobic analyte. The measured t(1/2) for methyl salicylate in
      distilled water was 2.0 min. The addition of 20% dextrose to distilled water
      increased the t(1/2) to 4.0 min while the 40% dextrose addition extended the
      t(1/2) to 9.0 min. The addition of dextrose to the water media effectively
      changes the partitioning media, increasing the resulting partition coefficient
      (Log P) values. Large changes in the Log P values were confirmed by the GC/FID
      analysis. In essence, water becomes a poor solvent for the analytes and diffusion
      is slowed from the hydrophobic MCT contained within the microcapsules as higher
      concentrations of dextrose is added to the water phase. Since methyl salicylate
      has a larger Log P(MCT: Water) value compared to acetophenone, the addition of
      dextrose extends the t(1/2) to a larger extent.

PMID- 19860546
TI  - The mesenchymal stem cell antigen MSCA-1 is identical to tissue non-specific
      alkaline phosphatase.
AB  - We have recently identified 2 distinct CD271(bright)MSCA-1(dim)CD56(+) and
      CD271(bright)MSCA-1(bright)CD56(-) MSC subsets in primary femur-derived bone
      marrow (BM), which differ in their expression pattern and morphology as well as
      in their clonogenic and differentiation capacity. Here, we show that MSCA-1 is
      identical to tissue non-specific alkaline phosphatase (TNAP), an ectoenzyme known
      to be expressed at high levels in liver, bone, and kidney as well as in embryonic
      stem (ES) cells. SDS-PAGE of WERI-RB-1 cell lysate and supernatant from
      phosphatidylinositol-specific phospholipase C (PI-PLC)-treated WERI-RB-1 cells
      resulted in the appearance of a prominent 68-kDa band. Matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDITOF MS) sequence
      analysis revealed TNAP-specific peptides. Screening of the MSCA-1-specific
      antibody W8B2 on HEK-293 cells transfected with the full-length coding sequence
      of TNAP showed specific reactivity with transfected but not with parent cell
      line. In addition, TNAP-specific mRNA expression was selectively detected in the
      transfectant line. In agreement with these findings, enzymatic activity of TNAP
      was exclusively detected in sorted MSCA-1(+) BM cells but not in the MSCA-1(-)
      negative fraction. Surface marker analysis revealed coexpression of the embryonic
      marker SSEA-3 but not SSEA-4, TRA-1-60, and TRA-1-81. In endometrium, TNAP is
      expressed at intermediate levels on CD146(+) cells and at high levels in the
      luminal space of glandular epithelia. Our results demonstrate that TNAP is a
      selective marker for the prospective isolation of BM-derived MSC and MSC-like
      cells in endometrium.

PMID- 19860547
TI  - Microencapsulation in genipin cross-linked gelatine-maltodextrin improves
      survival of Bifidobacterium adolescentis during exposure to in vitro
      gastrointestinal conditions.
AB  - To improve survival during exposure to adverse conditions, probiotic
      Bifidobacterium adolescentis 15703T cells were encapsulated in novel mono-core
      and multi-core phase-separated gelatine-maltodextrin (GMD) microspheres where the
      gelatine (G) phase was cross-linked with genipin (GP). Microscopy showed that
      encapsulated cells were exclusively associated with maltodextrin (MD) core(s).
      Small (average diameter 37 microm) and large (70 microm) GMD and G microspheres
      were produced by modulating factors (e.g. mixing speed, surfactant, GP and G
      concentrations) affecting the size, structural stability and phase-separation. In
      vitro sequential gastro-intestinal (GI) juice challenge experiments revealed
      increased survival of cells encapsulated in GMD ( approximately 10(6-7) cfu mL(
      1)) and G (approximately 10(5) cfu mL(-1)) microspheres as compared to free cells
      (approximately 10(4) cfu mL(-1)). In GMD microspheres, the bacteria derive energy
      from MD to survive during exposure to acid and bile salts. In conclusion, the
      novel food grade GMD microencapsulation formulation was shown to protect
      probiotic bifidobacteria from adverse conditions.

PMID- 19860548
TI  - Do speciation rates drive rates of body size evolution in mammals?
AB  - Recently, it has been shown with large data sets of extinct mammals that large
      bodied lineages experienced higher speciation and extinction rates; with extant
      mammals, it has been shown that body size evolution is accelerated during
      speciation. Therefore, it is interesting to investigate whether mammalian body
      size evolution is faster in large-bodied lineages. Phylogenetic analysis assuming
      size-independent speciation rates suggested that the rate of body size evolution
      increases with body size, whereas size differences in recent sister species (that
      are little affected by species turnover) appear to be independent of size. This
      supports the hypothesis that high rates of species turnover increase the rate at
      which interspecific differences accumulate in large-bodied clades, whereas rates
      of evolution in single lineages are approximately size invariant. Similarly,
      these findings support the notion that mammalian body size evolution is indeed
      concentrated in speciation events.

PMID- 19860544
TI  - Menstrual blood cells display stem cell-like phenotypic markers and exert
      neuroprotection following transplantation in experimental stroke.
AB  - Cell therapy remains an experimental treatment for neurological disorders. A
      major obstacle in pursuing the clinical application of this therapy is finding
      the optimal cell type that will allow benefit to a large patient population with
      minimal complications. A cell type that is a complete match of the transplant
      recipient appears as an optimal scenario. Here, we report that menstrual blood
      may be an important source of autologous stem cells. Immunocytochemical assays of
      cultured menstrual blood reveal that they express embryonic-like stem cell
      phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned
      media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the
      therapeutic potential of these cells, we used the in vitro stroke model of oxygen
      glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that
      were co-cultured with menstrual blood-derived stem cells or exposed to the media
      collected from cultured menstrual blood exhibited significantly reduced cell
      death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the
      media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation
      of menstrual blood-derived stem cells, either intracerebrally or intravenously
      and without immunosuppression, after experimentally induced ischemic stroke in
      adult rats also significantly reduced behavioral and histological impairments
      compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a
      source of "individually tailored" donor cells that completely match the
      transplant recipient, at least in women. The present neurostructural and
      behavioral benefits afforded by transplanted menstrual blood-derived cells
      support their use as a stem cell source for cell therapy in stroke.

PMID- 19860549
TI  - Insect rate-temperature relationships: environmental variation and the metabolic
      theory of ecology.
AB  - Much of the recent discussion concerning the form and underlying mechanistic
      basis of metabolic rate-temperature and development rate-temperature
      relationships has been precipitated by the development of the metabolic theory of
      ecology (MTE). Empirical tests of the theory's fundamental equation are an
      essential component of establishing its validity. Here, we test the temperature
      component of the fundamental equation of the MTE as it applies to metabolic rate
      and development rate, using insects as model organisms. Specifically, we test (i)
      whether mean activation energies, E, approximate the 0.65 eV value proposed by
      the proponents of the MTE and whether the range of values is tightly constrained
      between 0.6 and 0.7 eV, as they have argued; (ii) whether phylogenetic signal is
      apparent in the rate-temperature relationships; (iii) whether the slopes of the
      rate-temperature relationships show consistent, directional variation associated
      with environmental variables; and (iv) whether intra- and interspecific rate
      temperature relationships differ significantly. Because the majority of
      activation energy values fell outside the predicted range and rate-temperature
      relationships showed consistent directional variation correlated with large-scale
      climatic variation, we conclude that data from insects provide only limited
      support for the MTE. In consequence, we consider alternative explanations for
      variation in rate-temperature relationships.

PMID- 19860550
TI  - Directed growth of adult human white matter stem cell-derived neurons on aligned
      fibrillar collagen.
AB  - The nanoscale spatial organization of collagen fibrils as major constituents of
      extracellular matrices is believed to be crucial for neurite guidance in neural
      development and repair. To systematically study the influence of collagen fibril
      alignment, length, and density on human neuronal cell behavior, we used our novel
      technology to produce aligned collagen matrices by shear flow deposition using a
      microfluidic channel system and applied these surfaces to functional human
      neurons and glia derived from white matter neural stem cell cultures. Neurites on
      aligned collagen were highly oriented in the direction of the underlying fibrils,
      whereas neurites on nonaligned collagen or poly-d-lysine did not exhibit a
      preferred direction but formed a web-like morphology. Although the best alignment
      of collagen fibers in our study was seen using long fibrils at low density, the
      best neurite orientation was achieved on long fibrils at high density. Neurite
      outgrowth was enhanced on aligned collagen compared with nonaligned collagen or
      poly-d-lysine substrates, whereas neural differentiation and cell survival were
      not influenced by the type of substrate. Our data show that size and density of
      aligned collagen fibrils are crucial for axonal sprouting of human neural stem
      cell-derived neurons. The flexibility of our technology, allowing collagen matrix
      qualities to be adapted to the neuronal cell type of interest, is thus a major
      advantage for therapeutic reconstruction of axonal pathways in the central or
      peripheral nervous system.

PMID- 19860551
TI  - Periodontal tissue engineering and regeneration: current approaches and expanding
      opportunities.
AB  - The management of periodontal tissue defects that result from periodontitis
      represents a medical and socioeconomic challenge. Concerted efforts have been and
      still are being made to accelerate and augment periodontal tissue and bone
      regeneration, including a range of regenerative surgical procedures, the
      development of a variety of grafting materials, and the use of recombinant growth
      factors. More recently, tissue-engineering strategies, including new cell- and/or
      matrix-based dimensions, are also being developed, analyzed, and employed for
      periodontal regenerative therapies. Tissue engineering in periodontology applies
      the principles of engineering and life sciences toward the development of
      biological techniques that can restore lost alveolar bone, periodontal ligament,
      and root cementum. It is based on an understanding of the role of periodontal
      formation and aims to grow new functional tissues rather than to build new
      replacements of periodontium. Although tissue engineering has merged to create
      more opportunities for predictable and optimal periodontal tissue regeneration,
      the technique and design for preclinical and clinical studies remain in their
      early stages. To date, the reconstruction of small- to moderate-sized periodontal
      bone defects using engineered cell-scaffold constructs is technically feasible,
      and some of the currently developed concepts may represent alternatives for
      certain ideal clinical scenarios. However, the predictable reconstruction of the
      normal structure and functionality of a tooth-supporting apparatus remains
      challenging. This review summarizes current regenerative procedures for
      periodontal healing and regeneration and explores their progress and difficulties
      in clinical practice, with particular emphasis placed upon current challenges and
      future possibilities associated with tissue-engineering strategies in periodontal
      regenerative medicine.

PMID- 19860552
TI  - Role of the N- and C-terminal fragments of parathyroid-hormone-related protein as
      putative therapies to improve bone regeneration under high glucocorticoid
      treatment.
AB  - The parathyroid-hormone-related protein (PTHrP) is an important modulator of bone
      formation and bone remodeling. High and/or prolonged glucocorticoid (GC)
      treatments inhibit PTHrP expression in osteoblastic cells and bone formation and
      repair. We assessed the ability of the N- and C-terminal PTHrP fragments to
      restore the GC-altered bone regeneration after bone marrow ablation in mice.
      Animals were administered 3-methylprednisolone or vehicle and PTHrP (1-36) or
      PTHrP (107-139) every other day, beginning 4 days before marrow ablation in the
      tibia, and euthanized 12 days later. GC-treated mice showed in the ablated tibia
      a decrease in bone formation and in osteoblast and sclerostin-positive osteocyte
      numbers, reduced expression of osteoblastic factors, decreased osteogenesis of
      bone-marrow-derived cells, an increase in the numbers of multinucleated
      osteoclasts and adipocytes, and decreased cortical vascularization, as well as
      altered bone structure (measured by microcomputerized tomography) in the intact
      femur. These effects were reversed at least in part by either PTHrP peptide. The
      present novel findings support the use of both PTHrP peptides tested as putative
      bone regenerative therapies in GC-related bone diseases.

PMID- 19860553
TI  - A comparison of bimatoprost 0.03% versus the fixed-combination of latanoprost
      0.005% and timolol 0.5% in adult patients with elevated intraocular pressure: an
      eight-week, randomized, open-label trial.
AB  - INTRODUCTION AND PURPOSE: Bimatoprost and the fixed combination of latanoprost
      with timolol maleate are 2 medications widely used to treat glaucoma and ocular
      hypertension (OHT). The aim of the study is to compare the efficacy of these 2
      drugs in reducing intraocular pressure (IOP) after 8 weeks of treatment in
      patients with primary open angle glaucoma (POAG) or OHT. METHODS: In this
      randomized, open-label trial, 44 patients with POAG or OHT were allocated to
      receive either bimatoprost (1 drop QD) or latanoprost/timolol (1 drop QD).
      Primary outcome was the mean diurnal IOP measurement at the 8th week, calculated
      as the mean IOP measurements taken at 8:00 am, 10:00 am, and 12:00 pm Secondary
      outcomes included the baseline change in IOP measured 3 times a day, after the
      water-drinking test (performed after the last IOP measurement), and the
      assessment of side effects of each therapy. RESULTS: The mean IOP levels of
      latanoprost/timolol (13.83, SD = 2.54) was significantly lower than of
      bimatoprost (16.16, SD = 3.28; P < 0.0001) at week 8. Also, the change in mean
      IOP values was significantly higher in the latanoprost/timolol group at 10:00 am
      (P = 0.013) and 12:00 pm (P = 0.01), but not at 8:00 am (P = ns). During the
      water-drinking test, there was no significant difference in IOP increase
      (absolute and percentage) between groups; however, there was a significant
      decrease in mean heart rate in the latanoprost/timolol group. Finally, no
      significant changes in blood pressure and lung spirometry were observed in either
      groups. CONCLUSIONS: The fixed combination of latanoprost/timolol was
      significantly superior to bimatoprost alone in reducing IOP in patients with POAG
      or OHT. Further studies with large sample sizes should be taken to support the
      superior efficacy of latanoprost/timolol, as well as to better assess its profile
      of side effects.

PMID- 19860554
TI  - FT-Raman and energy dispersive X-ray fluorescence spectrometric analyses of
      enamel submitted to 38% hydrogen peroxide bleaching, an acidic beverage, and
      simulated brushing.
AB  - OBJECTIVE: This study aimed to investigate the effects on enamel surface treated
      with hydrogen peroxide bleaching and acidic soft drink immersion and/or brushing
      with whitening dentifrices. MATERIALS AND METHODS: Fifty-six standardized enamel
      slabs obtained from labial surfaces of bovine incisors were used. Enamel slabs
      were ground flat, polished, and randomly assigned to one of seven treatment
      groups: (1) control, in which no treatment was performed, (2) soft drink
      immersion, (3) 38% hydrogen peroxide bleaching, (4) simulated toothbrushing with
      whitening dentifrice, (5) soft drink immersion and bleaching, (6) soft drink
      immersion, bleaching, and toothbrushing, and (7) bleaching and toothbrushing. The
      mineral concentration of enamel surfaces was determined before and after
      treatments by means of Fourier transform (FT)-Raman spectroscopy and energy
      dispersive x-ray fluorescence spectrometry (EDXRF). Data were statistically
      analyzed by ANOVA and Tukey test (p < 0.05). RESULTS: Raman spectroscopy results
      indicated that enamel mineral content decreased after all treatments except in
      group 1, whereas EDXRF results exhibited mineral decrease in groups 3, 4, 5, and
      7. CONCLUSION: Bleaching alone or in combination with soft drink immersion and
      brushing decreases enamel mineral content.

PMID- 19860555
TI  - Effects of combined use of light irradiation and 35% hydrogen peroxide for dental
      bleaching on human enamel mineral content.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of the
      combined use of light irradiation (LIR, halogen light, or LED/diode laser) and
      35% hydrogen peroxide (35%HP) on human enamel mineral content. BACKGROUND DATA:
      The use of high-intensity light has been indicated for acceleration of the rate
      of chemical bleaching; however, it is not known whether LIR can promote
      additional effects on enamel surfaces during the bleaching. MATERIALS AND
      METHODS: One hundred enamel samples were obtained from third molars and randomly
      divided into 10 groups (n = 10). The control group (CG) remained untreated. Three
      whitening products were used: Whiteness HP Maxx, Pola Office, and Opalescence
      Xtra. Bleaching consisted of one session, and the products were applied three
      times to each specimen for 10 min each. The products were subjected, or not, to
      LIR during treatment with halogen light or LED/diode laser. The mineral
      concentration of enamel was determined before and after treatments using an FT
      Raman spectroscope (FT-RS), and the amount of calcium lost from the bleached
      enamel surfaces was quantified with an atomic absorption spectrometer (AAS).
      RESULTS: FT-RS results showed a decreased mineral content after all treatments,
      with the exception of Pola Office when irradiated with LED/diode laser and the
      CG. The losses of calcium detected for Pola Office and Opalescence Xtra were
      similar for the three situations (without or with light irradiations), whereas
      for Whiteness HP Maxx the lowest calcium loss was detected without LIR.
      CONCLUSION: Most of the bleaching treatments investigated, in combination with
      LIR or not, can reduce the mineral content of enamel surface. LIR increased the
      calcium loss for Whiteness HP Maxx; no effects were observed for Pola Office and
      Opalescence Xtra.

PMID- 19860556
TI  - The influence of perenniality and seed banks on polymorphism in plant-parasite
      interactions.
AB  - Antagonistic interactions, such as diseases, play an important role in natural
      populations. Understanding the mechanisms that promote long-term polymorphism at
      loci that are involved in host-parasite recognition is a fundamental problem in
      evolutionary ecology. Coevolution implies the existence of indirect frequency
      dependent selection because the fitnesses of parasite genotypes depend on the
      frequencies of host genes and vice versa. Polymorphism can be maintained in both
      organisms if there is also negative, direct, frequency-dependent selection, when
      natural selection for host resistance or parasite virulence declines with
      increasing frequency of that trait itself. In this article, using the gene-for
      gene relationship as a model, we show that two plant life-history traits, seed
      banks and perenniality with parasite density-dependent disease transmission,
      generate frequency-dependent selection on host resistance and are thus capable of
      stabilizing frequencies of coevolving host and parasite genes. The host
      population's response to selection by the parasite is modified by the
      contribution of past selective events stored in long-lived seed banks or in a
      growing population of perennial plants that have a long life span in the absence
      of disease. While fitness costs determine whether coevolutionary cycles occur in
      interacting host and parasite populations, the ecology of the two organisms
      determines whether stable polymorphism is maintained.

PMID- 19860557
TI  - Glutathione S-transferase M1 and T1 genes and susceptibility to chronic myeloid
      leukemia: a meta-analysis.
AB  - Variants of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes have been
      implicated as risk factors for chronic myeloid leukemia (CML). However, the
      genetic association studies that examined the relation between the null genotypes
      of GSTM1 and GSTT1 genes and risk of developing CML gave conflicting or
      inconclusive results. In an attempt to interpret these results, a meta-analysis
      of all available studies (nine studies, with 757 cases and 1959 controls) was
      performed. In the meta-analysis the pooled odds ratios (OR) were estimated using
      random effects models. The heterogeneity between studies, the sources of
      potential bias, and the consistency of genetic effects across ethnicities were
      explored. Cumulative meta-analysis was also performed. Overall, the meta-analysis
      showed nonsignificant association between GSTM1 null genotype and CML (OR = 1.00
      [0.83-1.20]) and lack of heterogeneity between the studies (p(Q) = 0.87). The
      association was also nonsignificant in Whites, East Asians, and Indians: OR =
      1.38 (0.43-4.46), 0.94 (0.65-1.35), and 1.16 (0.74-1.82), respectively. However,
      GSTT1 null genotype was associated with increased risk of CML (OR = 1.57 [1.13
      2.17]) and the heterogeneity between studies was significant (p(Q) = 0.04). In
      Indians, the association was significant (OR = 2.89 [1.56-5.35]) whereas in East
      Asians it was not significant (OR = 1.07 [0.74-1.54]). The combined GSTM1
      normal/GSTT1 null genotypes produced significant association (OR = 1.95 [1.17
      3.24]). Cumulative meta-analysis for GSTT1 gene showed an upward trend in risk
      effect, whereas the trend was downward in GSTM1. There was a differential
      magnitude of effect in large versus small studies. In conclusion, the accumulated
      evidence indicated an association between GSTT1 null genotype and CML.

PMID- 19860559
TI  - WU and KI polyomaviruses in the brains of HIV-positive patients with and without
      progressive multifocal leukoencephalopathy.
AB  - The polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified mainly in
      respiratory samples from children and immunosuppressed patients. Investigation of
      54 autopsy brain tissue samples from 22 subjects demonstrated that WUPyV DNA and
      KIPyV DNA could be detected in 1 of 4 human immunodeficiency virus (HIV)-positive
      individuals with progressive multifocal leukoencephalopathy (PML) and in 3 of 10
      HIV-positive individuals without PML, but not in 8 HIV-negative individuals.
      Viruses were localized in all regions of the central nervous system that were
      analyzed, that is, the cerebral hemispheres, cerebellum, pons, and medulla
      oblongata. No specific histopathological findings were found to be associated
      with the presence of WUPyV and KIPyV.

PMID- 19860558
TI  - Potential nonresponse bias in a clinical examination after initial screening
      using iron phenotyping and HFE genotyping in the hemochromatosis and iron
      overload screening study.
AB  - BACKGROUND: Little is known about the factors affecting participation in clinical
      assessments after HEmochromatosis and IRon Overload Screening. METHODS: Initial
      screening of 101,168 primary care patients in the HEmochromatosis and IRon
      Overload Screening study was performed using serum iron measures and
      hemochromatosis gene (HFE) genotyping. Using iron phenotypes and HFE genotypes,
      we identified 2256 cases and 1232 controls eligible to participate in a clinical
      examination. To assess the potential for nonresponse bias, we compared the
      sociodemographic, health status, and attitudinal characteristics of participants
      and nonparticipants using adjusted odds ratios (ORs) and 95% confidence interval
      (CI). RESULTS: Overall participation was 74% in cases and 52% in controls; in
      both groups, participation was highest at a health maintenance organization and
      lowest among those under 45 years of age (cases: OR = 0.68; 95% CI 0.53, 0.87;
      controls: OR = 0.59; 95% CI 0.44, 0.78). In controls only, participation was also
      lower among those over 65 years of age than the reference group aged 46-64 (OR =
      0.64; 95% CI 0.47, 0.88). Among cases, participation was higher in HFE C282Y
      homozygotes (OR = 3.98; 95% CI 2.60, 6.09), H63D homozygotes (OR = 2.79; 95% CI
      1.23, 6.32), and C282Y/H63D compound heterozygotes (OR = 1.82; 95% CI 1.03, 3.22)
      than in other genotypes, and lower among non-Caucasians and those who preferred a
      non-English language than in Caucasians and those who preferred English (p <
      0.0001). CONCLUSIONS: Subjects with greatest risk to have iron overload (C282Y
      homozygotes; cases > or =45 years; Caucasians) were more likely to participate in
      a postscreening clinical examination than other subjects. We detected no evidence
      of strong selection bias.

PMID- 19860561
TI  - Healthcare worker knowledge of measurement and documentation of tuberculin skin
      test reaction.
AB  - A cross-sectional survey of 210 healthcare workers at a pediatric teaching
      hospital was performed to assess knowledge of published guidelines for proper
      measurement and documentation of tuberculin skin test results. We conclude that
      many healthcare workers have inadequate knowledge for optimal measurement and
      documentation of tuberculin skin test results.

PMID- 19860560
TI  - Overproduction of acyloxyacyl hydrolase by macrophages and dendritic cells
      prevents prolonged reactions to bacterial lipopolysaccharide in vivo.
AB  - Although recognition of lipopolysaccharide (LPS) by the myeloid differentiation
      factor 2-Toll-like receptor 4 complex is important for triggering protective
      inflammatory responses in animals, terminating many of these responses requires
      LPS inactivation by a host lipase, acyloxyacyl hydrolase (AOAH). To test whether
      endogenously produced recombinant AOAH can modulate responses to LPS and gram
      negative bacteria, we engineered transgenic mice that overexpress AOAH in
      dendritic cells and macrophages, cell types that normally produce it. Transgenic
      mice deacylated LPS more rapidly than did wild-type controls. They also were
      protected from LPS-induced hepatosplenomegaly, recovered more quickly from LPS
      induced weight loss, and were more likely to survive when challenged with live
      Escherichia coli. Constitutive overexpression of AOAH in vivo hastened recovery
      from LPS exposure without interfering with the normal acute inflammatory response
      to this important microbial signal molecule. Our results suggest that the extent
      to which macrophages and dendritic cells produce AOAH may influence the outcome
      of many gram-negative bacterial diseases.

PMID- 19860562
TI  - A successful mandatory influenza vaccination campaign using an innovative
      electronic tracking system.
AB  - BACKGROUND: Although influenza vaccination of healthcare workers reduces
      influenza-like illness and overall mortality among patients, national rates of
      vaccination for healthcare providers are unacceptably low. We report the
      implementation of a new mandatory vaccination policy by means of a streamlined
      electronic enrollment and vaccination tracking system at the National Institutes
      of Health (NIH) Clinical Center. OBJECTIVE: To evaluate the outcome of a new
      mandatory staff influenza vaccination program. METHODS: A new hospital policy
      endorsed by all the component NIH institutes and the Clinical Center departments
      mandated that employees who have patient contact either be vaccinated annually
      against influenza or sign a declination specifying the reason(s) for refusal.
      Those who fail to comply would be required to appear before the Medical Executive
      Committee to explain their rationale. We collected in a database the names of all
      physician and nonphysician staff who had patient contact. When a staff member
      either was vaccinated or declined vaccination, a simple system of badge scanning
      and bar-coded data entry captured essential data. The database was continuously
      updated, and it provided a list of noncompliant employees with whom to follow up.
      RESULTS: By February 12, 2009, all 2,754 identified patient-care employees either
      were vaccinated or formally declined vaccination. Among those, 2,424 (88%) were
      vaccinated either at the NIH or elsewhere, 36 (1.3%) reported medical
      contraindications, and 294 (10.7%) declined vaccination for other reasons. Among
      the 294 employees without medical contraindications who declined, the most
      frequent reason given for declination was concern about side effects.
      CONCLUSIONS: Implementation of a novel vaccination tracking process and a
      hospital policy requiring influenza vaccination or declination yielded dramatic
      improvement in healthcare worker vaccination rates and likely will result in
      increased patient safety in our hospital.

PMID- 19860563
TI  - Epidemiology and impact of imipenem resistance in Acinetobacter baumannii.
AB  - BACKGROUND: Acinetobacter baumannii is an emerging gram-negative pathogen that
      can cause healthcare-acquired infections among patients. Treatment is complicated
      for cases of healthcare-acquired infection with A. baumannii resistant to
      imipenem. OBJECTIVE: To elucidate the risk factors for imipenem-resistant A.
      baumannii (IRAB) infection or colonization and to identify the effect of
      resistance on clinical and economic outcomes. METHODS: We analyzed data from 2
      medical centers of the University of Pennsylvania. Longitudinal trends in the
      prevalence of IRAB clinical isolates were characterized during the period from
      1989 through 2004. For A. baumannii isolates obtained from 2001 through 2006, a
      case-control study was conducted to investigate the association between prior
      carbapenem use and IRAB infection or colonization, and a cohort study was
      performed to identify the effect of IRAB infection or colonization on mortality,
      length of stay after culture, and hospital cost after culture. RESULTS: From 1989
      through 2004, the annual prevalence of IRAB isolates ranged from 0% to 21%.
      During the period from 2001 through 2006, there were 386 unique patients with A.
      baumannii isolates, and 89 (23.1%) had IRAB isolates. Prior carbapenem use was
      independently associated with IRAB infection or colonization (adjusted odds
      ratio, 3.04 [95% confidence interval, 1.07-8.65]). There was a borderline
      significant association between IRAB infection or colonization and mortality,
      although this association was limited to isolates recovered from blood samples
      (adjusted odds ratio, 5.30 [95% confidence interval, 0.81-34.59]). Compared with
      patients with imipenem-susceptible A. baumannii infection or colonization,
      patients with IRAB infection or colonization had a longer hospital stay after
      culture (median, 21 vs 16 days; P = .07) and greater hospital charges after
      culture (mean, $334,516 vs $276,059; P = .03). After controlling for patient
      location in an intensive care unit, transfer from another facility, and length of
      hospital stay before culture, there was no longer an independent association
      between IRAB infection or colonization and higher cost after culture and length
      of stay after positive culture result. CONCLUSIONS: Many A. baumannii isolates
      exhibit imipenem resistance, which is strongly associated with prior use of
      carbapenems. Given the high mortality rate associated with A. baumannii infection
      or colonization, interventions to curb further emergence of cases of IRAB
      infection and strategies to optimize therapy are needed.

PMID- 19860566
TI  - The association of low and high laser treatments on self-inflicted lip injury: a
      case report.
AB  - OBJECTIVE: Report a clinical case of surgical lip lesion removal owing to self
      injury in a 9-year-old male quadriplegic, spastic cerebral palsy (CP) patient
      using low and high lasers in association. BACKGROUND: Various management methods
      for oral trauma have been suggested, depending on the severity, frequency, and
      cause of injury, including medication, behavioral techniques, and oral appliances
      or dental extractions. METHODS: Initially, low-level laser therapy (LLLT) was
      used on the injured labial tissue measuring 2.2 cm externally and 3.4 cm in the
      internal mucosal, followed by surgical removal using a CO(2) laser. After 30
      days, a significant reduction in injury to the oral tissues was observed, and the
      region presented normal color and good healing conditions. CONCLUSION: The
      association of different laser therapies to remove and heal a lip lesion owing to
      self-injurious behavior was effective and promoted improvement in the patient's
      quality of life by establishing painless mastication.

PMID- 19860564
TI  - Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing
      K. pneumoniae.
AB  - BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is
      an emerging pathogen with serious clinical and infection control implications. To
      our knowledge, no study has specifically examined risk factors for KPC-producing
      K. pneumoniae or its impact on mortality. METHODS: To identify risk factors for
      infection or colonization with KPC-producing K. pneumoniae, a case-control study
      was performed. Case patients with KPC-producing K. pneumoniae were compared with
      control subjects with carbapenem-susceptible K. pneumoniae. A cohort study
      evaluated the association between KPC-producing K. pneumoniae and in-hospital
      mortality. RESULTS: Fifty-six case patients and 863 control subjects were
      identified. In multivariable analysis, independent risk factors for KPC-producing
      K. pneumoniae were (1) severe illness (adjusted odds ratio [AOR], 4.31; 95%
      confidence interval [CI], 2.25-8.25), (2) prior fluoroquinolone use (AOR, 3.39;
      95% CI, 1.50, 7.66), and (3) prior extended-spectrum cephalosporin use (AOR,
      2.55; 95% CI, 1.18, 5.52). Compared with samples from other anatomic locations,
      K. pneumoniae isolates from blood samples were less likely to harbor KPC (AOR,
      0.33; 95% CI, 0.12, 0.86). KPC-producing K. pneumoniae was independently
      associated with in-hospital mortality (AOR, 3.60; 95% CI, 1.87-6.91).
      CONCLUSIONS: KPC-producing K. pneumoniae is an emerging pathogen associated with
      significant mortality. Our findings highlight the urgent need to develop
      strategies for prevention and infection control. Limiting use of certain
      antimicrobials, specifically fluoroquinolones and cephalosporins, use may be
      effective strategies.

PMID- 19860568
TI  - Effect of two kinds of Er:YAG laser systems on root surface in comparison to
      ultrasonic scaling: an in vitro study.
AB  - OBJECTIVE: To evaluate the capacity of Er:YAG laser application to eliminate
      calculus from periodontally affected root surfaces compared with ultrasonic
      scaling (US), as well as the possible root damage incurred from both types of
      instrumentation. BACKGROUND DATA: The benefits of the use of the Er:YAG laser as
      a coadjuvant to conventional periodontal therapy have not yet been determined.
      MATERIALS AND METHODS: Forty human molars extracted due to advanced periodontal
      disease were used. A piezoelectric ultrasonic scaling (US) (Piezon Master EMS) at
      28,500 Hz was performed in the right area of the root. Two kinds of Er:YAG
      lasers, KaVo Key II Laser at 120-140 mJ and KaVo Key III Plus Laser equipped with
      a fluorescence-controlled feedback system applied at 160 mJ with and without
      fluorescence feedback control, were used in the left area. The amount of residual
      calculus and the number and diameter of exposed dentinal tubules were calculated
      by scanning electron microscopy (SEM). RESULTS: No differences were identified as
      to the amount of residual calculus between the four different laser treatments
      and US. The number of exposed dentinal tubules was higher as the output energies
      were increased for the laser treatments without feedback control, with a moderate
      increase in the mean diameter of the exposed dentinal tubules. Hardly any
      dentinal tubule exposure was observed as a result of treatment with feedback
      control. CONCLUSIONS: The capacity of the Er:YAG laser to remove calculus is
      comparable to US. Laser prototypes with feedback control allow a selective
      removal of calculus without any modification of the root surface.

PMID- 19860567
TI  - Root surface biomodification with Nd:YAG laser for the treatment of gingival
      recession with subepithelial connective tissue grafts.
AB  - BACKGROUND/AIM: Root surface biomodification has been used to treat gingival
      recession and periodontitis. The principle for this procedure is that removing
      the smear layer from the root surfaces exposes collagen fibers, which leads to
      improved healing. Clinical studies generally have failed to find any improvement
      in clinical parameters when using such procedures, however. The aim of this study
      was to evaluate and compare the outcome of gingival recession therapy using the
      subepithelial connective tissue graft (SCTG) with or without Nd:YAG laser
      application for root surface biomodification. MATERIALS AND METHODS: Thirty-four
      teeth in 17 patients with Miller Class 1 and 2 recession were treated with SCTG
      with (test group) or without (control group) the application of Nd:YAG laser (1
      W, 10 Hz, 100 mj, 60 s, 1064 nm). Clinical attachment level (CAL), recession
      depth (RD), recession width (RW), and probing depth (PD) were measured at
      baseline and six months postsurgery. RESULTS: Both treatments yielded significant
      improvements in terms of RD and RW decrease and CAL gain compared to baseline
      values. For test and control groups, the average root coverage was 33% and 77%,
      respectively (p < 0.05), and the complete root coverage was 18% and 65%,
      respectively (p < 0.05). The control group showed a greater reduction in RD and
      RW compared with the test group (p < 0.05). CONCLUSIONS: The use of Nd:YAG laser
      as a root surface biomodifier negatively affected the outcome of root coverage
      with the SCTG.

PMID- 19860569
TI  - Validating a nonacupoint sham control for laser treatment of knee osteoarthritis.
AB  - OBJECTIVE: The goals of the present study were to evaluate the effect and safety
      of combined 10.6 microm and 650 nm laser acupuncture-moxibustion on patients with
      knee osteoarthritis (OA) and to validate a nonacupoint sham control for assessing
      the effect of point specificity on the treatment. MATERIALS AND METHODS: A
      randomized, sham-controlled clinical trial was conducted in an outpatient
      clinical setting on patients with knee OA (n = 40). Laser irradiation was
      performed on acupoint Dubi (ST35) and a sham point three times a week for 4 wk.
      Outcome measurements were performed at baseline and at wk 2 and 4 using Western
      Ontario and McMaster Universities' Osteoarthritis Index (WOMAC). RESULTS: At the
      2-wk assessment, i.e., after 6 treatments, improvement in the WOMAC pain score of
      the acupoint group was significantly greater than that of the control group
      (49.21% vs. 11.99%, respectively; p = 0.021). However, there were no significant
      differences between the two groups in the WOMAC physical function score (p =
      0.129) or joint stiffness score (p = 0.705). No side effects were found during
      the trial. CONCLUSIONS: Combined 10.6-mum-650-nm laser acupuncture-moxibustion on
      acupoint ST35 is safe to use and was effective after 2-wk treatment, but not at
      the 4-wk assessment, in relieving knee OA pain compared to a nonacupoint sham
      control. A larger clinical trial to verify our findings is warranted.

PMID- 19860570
TI  - Effect of biostimulation on healing of bone defects in diabetic rats.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the effects of
      biostimulation on healing of bone defects in diabetic rats. STUDY DESIGN/MATERIAL
      AND METHODS: Twenty-eight Wistar rats weighting 250 to 300 g were used for this
      study. Diabetes was chemically induced with streptozotocin, and 14 nondiabetic
      and 14 diabetic rats were included in the study. The distal epiphysis of the
      right and left femurs of the diabetic rats were perforated with a surgical bone
      drill. This surgical procedure was performed on the left femurs of normal rats
      too. The wound on the right side of each diabetic rat received laser stimulation.
      The left femur of each nondiabetic (normal) rat served as a control. The rats
      were assigned to three experimental groups: (1) normal bur (control group); (2)
      diabetic bur; (3) diabetic bur + biostimulation. RESULTS: There was a significant
      difference among all groups in substantia spongiosa formation on day 10.
      According to the Mann-Whitney U test, there was a difference between Groups 1 and
      2. A significant difference was noted between Groups 2 and 3 as well as between
      Groups 1 and 3 and between Groups 2 and 3 in union at 20 d of healing.
      CONCLUSIONS: Substantia spongiosa formation was slightly more evident in Groups 1
      and 3 than in Group 2. Also, there was more union in Group 3 than in the other
      groups on day 20. As a result, it can be concluded that low-level laser therapy
      (808 nm laser at 10 J/cm(2)) can have a beneficial effect on spongiosa in
      diabetic bone repair when five treatments are administered with 2 d intervals
      between treatments.

PMID- 19860571
TI  - Evaluation of oxygen consumption of culture medium and in vitro photodynamic
      effect of talaporfin sodium in lung tumor cells.
AB  - OBJECTIVE: Successful photodynamic therapy (PDT) requires high production of
      radical ions and singlet oxygen to kill target cells. However, PDT also induces
      angiogenesis through production of vascular endothelial growth factor (VEGF),
      which promotes cell regrowth and vascularization. In this study, we evaluated the
      importance of oxygen in PDT by measuring oxygen consumption, photosensitizer
      bleaching, and reactive oxygen species (ROS) production in the culture medium,
      and VEGF secretion either during or after PDT treatment using mouse Lewis lung
      carcinoma (LLC) cells. BACKGROUND DATA: Local hypoxia is induced under a low
      oxygen environment. Oxygen is consumed when ROS and singlet oxygen are produced
      during PDT. The effect of oxygen consumption on cytotoxicity and VEGF secretion
      has not been clarified. MATERIALS AND METHODS: Mouse Lewis lung carcinoma (LLC)
      cells treated with the photosensitizer talaporfin sodium were irradiated by a
      continuous wave semiconductor laser (wavelength, 664 +/- 1 nm). We used oxygen
      microelectrode for oxygen measurement, a fluorescent probe to detect ROS, MTT
      assay to evaluate the PDT efficacy, and enzyme-linked immunosorbent assay to
      measure VEGF concentration. RESULTS: During PDT, oxygen consumption was higher
      with high doses of talaporfin sodium solution compared with low doses. In
      addition, the fluorescence of 2-[6-(4'-amino)phenoxy-3H-xanthen-3-on-9-yl]benzoic
      acid, a probe for highly reactive oxygen species such as hydroxyl radicals (*OH),
      dramatically increased when the dose of talaporfin sodium solution was high.
      Moreover, VEGF concentration increased after PDT due to hypoxia in a manner
      dependent on photosensitizer concentration. CONCLUSION: These results indicate
      that the efficiency of PDT might be improved by sustaining a replete oxygen
      environment during PDT, not only for ROS and singlet oxygen production, but also
      for inhibiting neoangiogenesis.

PMID- 19860572
TI  - Low-level laser therapy for implants without initial stability.
AB  - OBJECTIVE: This study evaluated the effect of low-level infrared laser on removal
      torque values of implants with poor initial stability inserted in rabbit tibias.
      BACKGROUND DATA: It is important to analyze the effects of laser radiation on
      bone repair when low-quality bone and implants with poor initial stability are
      used. MATERIALS AND METHODS: Thirty male white New Zealand rabbits (Oryctolagus
      Cuniculus) about 2 mo old and weighing 1.5-2.0 kg were used. Machined implants
      with poor initial stability were inserted in the tibia of each animal. Animals
      were randomly divided into two groups: laser irradiated and laser nonirradiated.
      Each group was further divided into three subgroups, according to the day the
      animals were killed: 15, 30, or 45 d. Torque values were measured with an axial
      digital torquemeter that applied counter-torque. The Student's t-test was used to
      calculate means and standard deviations for the comparisons between laser and
      control groups. RESULTS: A significant increase (p = 0.050) in removal torque
      values was found in the group of laser-irradiated implants at 15 and 30 d when
      compared with the control groups. At 45 d, no significant differences were found.
      CONCLUSION: In this study, low-level laser therapy promoted the osseointegration
      of implants with poor initial stability, particularly in the initial stages of
      bone healing.

PMID- 19860573
TI  - Nonoperative management of blunt abdominal trauma: have we gone too far?
AB  - BACKGROUND: The paradigm shift in the management of blunt abdominal trauma has
      been to become less invasive with both diagnostic tools and management. Avoidance
      of a laparotomy with its short-term and long-term risks is of obvious benefit to
      the patient. METHOD: Review of the pertinent literature. RESULTS: Most blunt
      hepatic and splenic injuries are managed nonoperatively. Management of blunt
      splenic injury with observation and organ preservation will avoid the lifelong
      risk of overwhelming postsplenectomy infection. However, what are the risks? Does
      nonoperative management simply delay laparotomy? The answer is no. The pendulum
      has swung too far toward observation. Most patients with blunt hepatic injury,
      irrespective of the grade, are hemodynamically stable and can be observed. On the
      other hand, high-grade injury (IV and V) often necessitates operation or
      management of complications by interventional radiology or gastroenterology
      procedures. When hepatic injury necessitates laparotomy because of hemodynamic
      instability, the operation is technically challenging, with a significant risk of
      death. As shown by large studies, the risk of failure of nonoperative management
      of blunt splenic injury includes preventable deaths. Factors in such deaths
      include inappropriate clinical decision-making, false-negative diagnostic
      studies, and initial misreading of computed tomography scans. CONCLUSION: Safe
      nonoperative management requires adherence to cardinal surgical principles,
      examination and re-examination of the patient, and fastidious clinical judgment.

PMID- 19860574
TI  - Treatment of complicated skin and soft tissue infections.
AB  - BACKGROUND: Skin and soft tissue infections (SSTIs) may produce substantial
      morbidity and mortality rates, particularly those classified as complicated or
      necrotizing. OBJECTIVE: To weigh the strength of recommendations using the Grades
      of Recommendation, Assessment, Development and Evaluation (GRADE) methodology and
      to provide evidence-based recommendations for diagnosis and management for SSTIs.
      DATA SOURCES: Computerized identification of published research and review of
      relevant articles. STUDY SELECTION: All published reports on the management of
      complicated and necrotizing SSTIs were evaluated by an expert panel of members of
      the Surgical Infection Society according to published guidelines for evidence
      based medicine. The quality of the evidence was judged by the GRADE methodology
      and criteria. Practice surveys, pharmacokinetic studies, and reviews or
      duplicative publications presenting primary data already considered were excluded
      from analysis. DATA EXTRACTION: Information on demographics, study dates,
      microbiology findings, antibiotic type, surgical interventions, infection-related
      outcomes, and the methodologic quality of the studies was extracted. Results were
      submitted to the Therapeutic Agents Committee of the Surgical Infection Society
      for review prior to creation of the final consensus document. DATA SYNTHESIS:
      Current surgical and antibiotic management of complicated SSTIs is based on a
      small number of studies that often have insufficient power to draw well-supported
      conclusions, with the exception of antimicrobial therapy for non-necrotizing soft
      tissue infections, for which ample data are available.

PMID- 19860575
TI  - A novel training model for laparoscopic partial nephrectomy using porcine kidney.
AB  - PURPOSE: The purpose of this study was to create a simple model for teaching
      laparoscopic partial nephrectomy (LPN) for duplicating the blood supply setting
      and main technical points of the procedure. MATERIALS AND METHODS: A fresh
      porcine kidney was placed on an unfolded metallic box to help trainees observe,
      practice, and develop LPN skills in both tumor incision and suturing. The
      metallic box was specially designed not only for fixing and positioning the
      kidney but also for storing the outflow of the kidney while its artery was kept
      artificially infused. A spherical renal parenchyma excision about 2 cm in
      diameter was initially made and the suture-repairing work followed. This model
      was used by trainees who had fair laparoscopic competency after completing dry
      laboratory training programs. During a 20-day training period the trainees were
      assessed with respect to the time needed to complete LPN. A mentor-trainee
      fellowship program was planned to guarantee the success of the operations and the
      quality of LPN. RESULTS: There was a good reduction in the total operative time
      from the fourth to the last attempt. There was also increasing improvement in the
      quality of the incision suturing during the attempts. By the end of 10 attempts
      all trainees were more confident in completing a good quality LPN in a mean time
      of 28.4 minutes. CONCLUSION: This model not only offers trainees the
      opportunities to acquire the skills necessary for LPN but also provides for more
      economical practice by using easily available porcine kidney.

PMID- 19860576
TI  - Association of EGFR and HER2 polymorphisms with risk and clinical features of
      thyroid cancer.
AB  - The epidermal growth factor receptor family plays a critical role in the control
      of many physiological processes. Genetic alterations and/or variations in the
      gene encoding these receptors have been implicated in a variety of human cancers.
      In this study we evaluate the association of two single-nucleotide polymorphisms
      (SNP), R497K and I655V, of the EGFR and HER2 genes, respectively, with thyroid
      cancer risk. The analysis was performed with 302 healthy individuals and 106
      thyroid cancer patients. No significant difference was found in the allelic and
      genotypic frequency distribution of the SNP R497K between the control and patient
      groups. While for the SNP I655V, the allele G is more frequent in patients than
      in controls and was associated with an increased risk of thyroid cancer (odds
      ratio = 1.88; 95% confidence intervals: 1.18-3.01; p = 0.007). We have also
      investigated the relationship between these two polymorphic sites and
      clinicopathological characteristics such as thyroid-stimulating hormone level,
      off-thyroxin, serum thyroglobulin, tumor histology, metastasis, tumor status,
      tumor stage, and survival. No significant association was observed. Tumor status
      was found significantly associated with HER2 I655V as well as with two previously
      studied markers in the thyroid hormone receptor A and estrogen receptor 1 (ESR1)
      genes (D17S2189 and D6S440, respectively). We also report a correlation between
      thyroglobulin level and genotypes for SNP rs2228480 in exon 8 of the ESR1 gene.
      In conclusion, our results suggest that the SNP HER2 I655V, but not the EGFR
      R497K, was associated with thyroid cancer risk.

PMID- 19860577
TI  - Revised American Thyroid Association management guidelines for patients with
      thyroid nodules and differentiated thyroid cancer.
AB  - BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated
      thyroid cancer is becoming increasingly prevalent. Since the publication of the
      American Thyroid Association's guidelines for the management of these disorders
      was published in 2006, a large amount of new information has become available,
      prompting a revision of the guidelines. METHODS: Relevant articles through
      December 2008 were reviewed by the task force and categorized by topic and level
      of evidence according to a modified schema used by the United States Preventative
      Services Task Force. RESULTS: The revised guidelines for the management of
      thyroid nodules include recommendations regarding initial evaluation, clinical
      and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine
      needle aspiration biopsy results, and management of benign thyroid nodules.
      Recommendations regarding the initial management of thyroid cancer include those
      relating to optimal surgical management, radioiodine remnant ablation, and
      suppression therapy using levothyroxine. Recommendations related to long-term
      management of differentiated thyroid cancer include those related to surveillance
      for recurrent disease using ultrasound and serum thyroglobulin as well as those
      related to management of recurrent and metastatic disease. CONCLUSIONS: We
      created evidence-based recommendations in response to our appointment as an
      independent task force by the American Thyroid Association to assist in the
      clinical management of patients with thyroid nodules and differentiated thyroid
      cancer. They represent, in our opinion, contemporary optimal care for patients
      with these disorders.

PMID- 19860578
TI  - Consensus statement on the terminology and classification of central neck
      dissection for thyroid cancer.
AB  - BACKGROUND: The primary goals of this interdisciplinary consensus statement are
      to review the relevant anatomy of the central neck compartment, to identify the
      nodal subgroups within the central compartment commonly involved in thyroid
      cancer, and to define a consistent terminology relevant to the central
      compartment neck dissection. SUMMARY: The most commonly involved central lymph
      nodes in thyroid carcinoma are the prelaryngeal (Delphian), pretracheal, and the
      right and left paratracheal nodal basins. A central neck dissection includes
      comprehensive, compartment-oriented removal of the prelaryngeal and pretracheal
      nodes and at least one paratracheal lymph node basin. A designation should be
      made as to whether a unilateral or bilateral dissection is performed and on which
      side (left or right) in unilateral cases. Lymph node "plucking" or "berry
      picking" implies removal only of the clinically involved nodes rather than a
      complete nodal group within the compartment and is not recommended. A therapeutic
      central compartment neck dissection implies that nodal metastasis is apparent
      clinically (preoperatively or intraoperatively) or by imaging (clinically N1a). A
      prophylactic/elective central compartment dissection implies nodal metastasis is
      not detected clinically or by imaging (clinically N0). CONCLUSION: Central neck
      dissection at a minimum should consist of removal of the prelaryngeal,
      pretracheal, and paratracheal lymph nodes. The description of a central neck
      dissection should include both the indication (therapeutic vs.
      prophylactic/elective) and the extent of the dissection (unilateral or
      bilateral).

PMID- 19860579
TI  - What characteristics do service users with intellectual disability value in
      direct support staff within residential forensic services?
AB  - BACKGROUND: This study explores the perceptions of a group of adults with
      intellectual disability regarding direct support staff. METHOD: Semi-structured
      interviews relating to experiences of direct support staff were developed from
      two focus groups. These interviews were conducted with 11 adults with
      intellectual disability residing within a forensic inpatient service. RESULTS:
      Interpretative Phenomenological Analysis (IPA) revealed two superordinate themes;
      namely, staff relationship factors and positive and negative attributes of staff.
      The participants valued relationships with staff based on qualities such as
      honesty, trust, and a caring, nurturing manner that enabled individuals to feel
      safe. Staff characteristics such as immaturity, inexperience, and a short temper
      appeared to lead to feelings of discontentment amongst the participants.
      CONCLUSIONS: The implications of the findings are discussed in relation to
      clinical practice, staff recruitment, and training.

PMID- 19860580
TI  - Parent adaptation to and parenting satisfaction with children with intellectual
      disability in the United Arab Emirates.
AB  - BACKGROUND: This research investigated the impact that children with intellectual
      disability in the United Arab Emirates (UAE) may have on their families. METHOD:
      Sixty-three parents completed three scales related to parent stress, ways of
      coping, and parenting satisfaction. RESULTS: There were significant relationships
      between emotional-focused coping and family adaptation and between problem
      focused coping and parenting satisfaction. There were no significant
      relationships between other predictor and outcome measures. CONCLUSION: This
      research advances our understanding of family responses to a child with
      intellectual disability in Arab cultures.

PMID- 19860581
TI  - Serum leptin levels depend on allergen exposure in patients with seasonal
      allergic rhinitis.
AB  - Several studies have outlined a possible relationship between an increased body
      mass index (BMI) and respiratory allergic diseases, such as asthma and rhinitis.
      There are conflicting data about the role for leptin in allergic rhinitis.
      Therefore, the aim of the study was to evaluate the serum leptin levels in
      patients with seasonal allergic rhinitis (SAR), enrolled during and outside the
      pollen season, and in a group of healthy controls. The study included 137
      subjects; 62 symptomatic SAR patients evaluated in season, 41 symptomless SAR
      patients out season, and 34 normal subjects. All subjects were consecutively
      evaluated. A skin prick test and blood sampling for assessing serum leptin levels
      were performed in all subjects. After analysing genders separately, symptomatic
      male patients had significantly higher levels than symptomless and normal
      subjects (p = 0.0004 and 0.0031 respectively), symptomatic female patients showed
      significantly higher levels than normal females (p = 0.0002). This study provides
      the evidence that leptin serum levels depend on allergen exposure in SAR
      patients.

PMID- 19860583
TI  - The Thomsen-Friedenreich antigen and alphaGal-specific human IgG glycoforms:
      concanavalin A reactivity and relation to survival of cancer patients.
AB  - Glycan structures of IgG strongly influence the affinity for Fcgamma receptors
      and antibody effector functions. However, no particular attention has been paid
      yet to the glycosylation of tumor antigen-specific IgG. The objectives of this
      study were (i) to investigate the concanavalin A lectin (ConA) reactivity of
      human anti-Thomsen-Friedenreich (TF) and anti-alphaGal specific IgG in gastric
      cancer patients and healthy controls and (ii) to evaluate whether the ConA
      reactivity of anti-TF and anti-alphaGal specific IgG is associated with the
      survival rate of patients with cancer. Total IgG was purified from the sera of
      patients with gastric cancer and healthy blood donors. The anti-TF and anti
      alphaGal glycotope specific IgG were detected with ELISA using synthetic
      saccharide-polyacrylamide conjugates as antigen. In parallel plate, the ConA
      reactivity of the anti-TF or anti-alphaGal IgG was determined and the ConA index
      was calculated. Results show that serum anti-TF specific IgG antibodies of
      patients with cancer contain significantly higher content of ConA positive IgG
      glycoform compared to IgG of controls. No correlation between the ConA reactivity
      of anti-TF IgG and anti-alphaGal IgG was observed. High level of anti-TF IgG ConA
      reactivity was associated with a significantly lower survival rate of patients
      with gastric cancer.

PMID- 19860582
TI  - Immunotherapy of autoimmune diabetes by nasal administration of tandem glutamic
      acid decarboxylase 65 peptides.
AB  - Mucosally induced tolerance is an attractive strategy for immunotherapy of
      autoimmune diseases. Treatment of nonobese diabetic (NOD) mice with a mixture of
      autoantigen peptides is better geared toward slowing the progression of late
      stage type 1 diabetes (T1D) than treatment with any of the peptides alone. In
      this study, we constructed a fusion protein CTB-GADIII. It contains cholera toxin
      B subunit (CTB) and three tandem peptides derived from glutamic acid
      decarboxylase 65 (GAD65), p217-236, p524-538 and p290-306. The purified renatured
      pentamer fusion protein was effective in inhibiting the development of diabetes
      in NOD mice when the mice were nasally immunized three times (8w, 10w and 12w).
      Prevention of diabetes was associated with special humoral immune tolerance
      against tandem peptides GADIII. These data indicate that using CTB as a vaccine
      carrier, tandem GAD65 peptides can prevent T1D in NOD mice at the late stage of
      disease.

PMID- 19860584
TI  - A novel splice variant of FR4 predominantly expressed in CD4+CD25+ regulatory T
      cells.
AB  - Folate receptor 4 (FR4) is recently found as a lymphoid tissue specific protein.
      In this study, we have identified an alternative splicing variant of the FR4 gene
      from murine splenocytes, termed FR4v, which is almost identical to FR4 cDNA
      sequence except with the retained 108 bp intron 3 between exon 3 and 4 of FR4
      gene. FR4v mRNA encodes a larger protein than FR4 and is constitutively expressed
      on CD4(+)CD25(+) regulatory T cell (Treg) membrane via a GPI anchor mechanism.
      Whether FR4v plays a redundant or unique functional role in Tregs should be
      investigated further in the future.

PMID- 19860585
TI  - Lipopolysacchride-treated mammary carcinomas secrete proinflammatory chemokines
      and exhibit reduced growth rates in vivo, but not in vitro.
AB  - Toll-like receptors (TLR) are pattern recognition receptors that play a pivotal
      role in the initiation of immune responses. Here we report that the murine
      mammary carcinoma 4T1 constitutively expressed genes encoding TLR2, 3, 4 and 5.
      Moreover, treatment of the 4T1 cell line with peptidoglycan (PGN), polyinosinic
      polycytidylic acid (Poly(I:C)) or lipopolysaccharide (LPS), agonists for TLR2, 3
      or 4 respectively, induced nuclear translocation of NFkappaB and secretion of
      CCL2, CCL5 and CXCL1 in a dose dependent manner. Although treating the tumor
      cells with the TLR agonists did not modulate growth or viability of the tumor
      cells in vitro, 4T1 exhibited a decreased growth rate in vivo following treatment
      with LPS that was dependent upon the presence of CD8(+) T cells. Analysis of 3
      additional murine mammary carcinomas revealed that they also secreted CCL2, CCL5
      and CXCL1 in response to TLR agonist treatment, and LPS treated 168 and SM1
      tumors exhibited decreased growth rates in vivo, but not in vitro. These data
      indicated that 4 out of 4 murine mammary carcinomas secreted proinflammatory
      chemokines following treatment with TLR agonists, and 3 out of 4 of the mammary
      carcinomas responded to LPS treatment in a manner that decreased tumor growth in
      vivo.

PMID- 19860586
TI  - Isolation of an antigen fraction from Setaria cervi adults having potential for
      immunodiagnosis of human filariasis.
AB  - Crude antigenic preparations from heterologous filarial parasites gave false
      positive results because of complex nature of these antigens and their cross
      reactivity with other helminth parasites. In the present study, efforts have been
      made to isolate and characterize the antigens from Setaria cervi important for
      diagnostic purposes. The fractionation of S. cervi somatic antigenic preparation
      on Sephacryl S-200 resulted in separation of three major antigenic peak
      fractions. Crossed immunoelectrophoretic analysis, using immune rabbit serum,
      revealed 13-14 antigens in SFP-I pool fraction, which showed high reactivity with
      filarial patients sera as compared to other two pool fractions. This SFP-I
      fraction was further purified by DEAE-Cellulose column chromatography. Out of the
      4 antigen pool fractions, DFP-IV fraction showed high ELISA reactivity with
      filarial patient serum pool (Wuchereria bancrofti and Brugia malayi) as compared
      to other fractions. The SDS-PAGE analysis of DFP-IV fraction revealed 2 major and
      1 minor protein bands (mol. wt. range 65-70 kDa). Crossed immunoelectrophoresis
      also showed the presence of 3 antigenic peaks in DFP-IV fraction. The purified
      DFP-IV fraction showed high reactivity with filarial patients sera but did not
      cross-react with sera from ascaris and hookworm infections thereby suggesting the
      filaria-specificity and potential for immunodiagnosis of human filariasis.

PMID- 19860587
TI  - Prime-boost immunization of codon optimized HIV-1 CRF01_AE Gag in BCG with
      recombinant vaccinia virus elicits MHC class I and II immune responses in mice.
AB  - The HIV-1 CRF01_AE gag gene was modified by codon restriction for Mycobacterium
      spp. and transformed into BCG; and it was designated as rBCG/codon optimized
      gagE. This produced 11 fold higher HIV-1 gag protein expression than the
      recombinant native gene rBCG/HIV-1gagE. In mice, CTL activity could be induced
      either by a single immunization of the codon optimized construct or by using it
      as a priming antigen in the prime-boost modality with recombinant Vaccinia virus
      expressing native HIV-1 gag. Specific secreted cytokine responses were also
      investigated. Only when rBCG gag was codon optimized did the prime-boost
      immunization produce significantly enhanced IFN-gamma and IL-2 secretion
      indicating recognition via CD4+ and CD8+ T cells, and these responses seemed to
      be codon optimized immunogen dose-responsive. On contrary, the prime-boost
      vaccination using an equal amount of native rBCG/HIV-1gagE instead, or a single
      rBCG/codon optimized gagE immunization, had no similar effect on the cytokine
      secretion. These findings suggest that the use of recombinant codon BCG construct
      with recombinant Vaccinia virus encoding CRF01_AE gag as the prime-boost HIV
      vaccine candidate, will induce CD4+ Th1 and CD8+ T cell cytokine secretions in
      addition to enhancing CD8+ CTL response.

PMID- 19860588
TI  - Differences in intraepithelial lymphocytes in the proximal, middle, distal parts
      of small intestine, cecum, and colon of mice.
AB  - We have previously reported the regional differences in the intraepithelial
      lymphocytes (IELs) present in the small intestine of mice. In this study, we
      further investigated these differences on the basis of our previous findings and
      studied the entire intestine, including the cecum and colon. Most of the
      significant differences in phenotypic compositions were found between the small
      and large intestines, although some differences were found among the different
      parts of the small and large intestines. In particular, the composition of the
      subsets in alphabeta T cells and gammadelta T cells clearly differed between the
      small and large intestines. For example, in alphabeta T cells, the percentages of
      double negative (DN) and CD8alphaalpha(+) cells were higher in the large
      intestine, that of CD8alphabeta(+) cells was higher in the small intestine, and
      those of CD4(+) and CD4(+) CD8alphaalpha(+) double positive (DP) cells were
      higher in the distal part of the small intestine. In gammadelta T cells, the
      percentage of CD8alphaalpha(+) cells was higher in the small intestine and that
      of DN cells was higher in the large intestine. These results indicate that the
      differences between IELs in the small and large intestines are discontinuous.

PMID- 19860589
TI  - The influences of CD14 -260C>T polymorphism on survival in ICU critically ill
      patients.
AB  - In order to analyze the effect of the two different versions of the cluster of
      differentiation 14 (CD14) receptor recognizing gene on survival, we determined
      the -260C>T single nucleotide polymorphism (SNP) frequencies in 514 critically
      ill patients. We compared the -260TT homozygotes with -260C allele carriers (
      260CC and -260CT genotypes) and we demonstrated--260TT patients had the highest
      survival rate (82% vs 64%; p < 0.001; OR = 2.52, 95% CI = 1.43-4.46). We
      performed binary logistic regression, incorporating both -260C>T genotype groups
      and the main clinical predictors to exclude other risk factors that could
      influence the outcome from critical illness: higher age, APACHE II score, and
      length of stay at hospital, and the occurrence of sepsis and septic shock were
      risk factors to Intensive Care Unit (ICU) patient's mortality, but the -260TT
      genotype was protective factor toward survival (p = 0.001; OR = 3.08 95%CI = 1.54
      5.98). Among septic and septic shock patients, -260TT genotype was also
      protective factor toward survival (p = 0.001; OR = 3.11 95%CI = 1.63-6.66 to
      septic patients, and p = 0.001; OR = 3.80 95%CI = 1.68-8.58 to patients with
      septic shock). Our results and our hypothesis suggest that the higher -260TT
      genotype frequency in ICU survivor patients is possibly explained by a beneficial
      effect on innate immunity signaling.

PMID- 19860590
TI  - The frequency of HLA class I and II alleles in Pakistani patients with aplastic
      anemia.
AB  - Hematological disorders like Aplastic anemia are quite frequent in Pakistan.
      Human leukocyte antigen (HLA) system, have been implicated in the development of
      Aplastic anemia in various population-based studies, The aim of this study was to
      determine the role of the HLA Class I and Class II alleles in genetic
      susceptibility to Aplastic anemia in Pakistani patients. HLA A*, B* and DRB1*
      alleles were analyzed, in 61 Pakistani patients (Females n = 22, Males n = 39)
      and the control group consisted of 200 ethnically matched individuals (Females n
      = 89, Males n = 111). The allele frequency of DRB1*15 was found significantly
      higher in patients 0.36 (p = 0.001 with odds ratio = 1.97), as compared to the
      controls 0.212. Although DRB1*03 percent frequency was significantly higher in
      controls 0.175 (p = 0.023) with odds ratio = 0.514, as compared to patients
      0.106.Therefore DRB1*15 emerged as a susceptible allele and DRB1*03 as a
      protective allele in Pakistani Aplastic anemia patients and control samples. No
      significant difference was found in allele frequencies of other HLA class I and
      HLA class II alleles for both patients and controls. Three haplotypes A*02 B*40
      DRB1*15 (p = 0.021), A*31 B*51 DRB1*13 (p = 0.12) and A*33 B*58 DRB1*15 (p =
      0.000) showed significant variations in the two groups.

PMID- 19860591
TI  - Tumor burden influences cytotoxic T cell development in metastatic breast cancer
      patients--a phase I/II study.
AB  - The influence of tumor burden on the generation of tumor antigen-specific
      cytotoxic T-lymphocytes (CTL) was investigated in a phase I/II clinical adoptive
      immunotherapy trial. Four previously treated metastatic breast cancer patients,
      two with macroscopic disease and two with no evidence of disease, in complete
      remission (CR), were enrolled. Each apheretic peripheral blood mononuclear cell
      (PBMC) sample was stimulated twice with MUC-1 before infusion back into the
      patients. CTL responses against MCF-7 cell line and cytokine production were
      measured before infusion. Patients received two monthly CTL infusions and were
      monitored for toxicity, tumor response as well as tumor marker levels. The CTL
      generated from patients with high tumor burdens had less cytokine production and
      lower cytotoxicity of MCF-7 than the CTL of patients in CR. The differences
      between the two groups were observed after the two MUC1 in vitro stimulations of
      the cells obtained in first apheresis. This difference increased after the two
      MUC1 stimulations of the cells obtained in the second apheresis. The cytotoxicity
      function was sustained from the first infusion to the second apheresis only for
      the patients in CR. This suggests that tumor burden had an inverse effect on the
      function of the generated CTL.

PMID- 19860592
TI  - Comparative study of antinuclear antibody detection by indirect
      immunofluorescence and enzyme immunoassay in lupus patients.
AB  - To evaluate the value of immunofluorescent and ELISA techniques in early
      diagnosis of systemic lupus erythematosus (SLE) and to find out whether there is
      a correlation between Antinuclear antibodies (ANA) pattern and prognosis by
      observing clinical score changes using British Isles Lupus Assessment Group
      score. The study included 75 SLE patients, 11 disease control group, and 18
      healthy control group. ANA and ds-DNA antibodies detection were done by ELISA and
      Immunofluorescence for all groups. Immunofluorescence technique is more sensitive
      for ANA and ds-DNA detection than ELISA technique (100% versus 90.7%,and 93%
      versus 89.3% respectively); ELISA showed 89.7 % specificity for ANA detection
      compared to 86.2% for Immunofluorescence, and both have 100% specificity for ds
      DNA detection ;homogenous ANA pattern, showed statistically significant higher
      BILAG score compared to speckled pattern either at the start of the study or
      after the follow up period (p = 0.000); and ds-DNA titer showed statistically
      significant decrease in titer after therapy (p = 0.01). ANA detection by
      Immunofluorescence is more sensitive and effective screening assay in patients
      with clinical features of SLE and both ds-DNA titer by ELISA and BILAG score for
      severity index are considered the best markers for follow-up.

PMID- 19860595
TI  - Statement of retraction.

PMID- 19860593
TI  - A specific signalling signature characterizes the development of naturally
      occurring and antigen-specific regulatory T cells.
AB  - The molecular signals involved in the generation of thymic regulatory T cells
      (Treg) still remain controversial. It has been proposed that high avidity
      interactions are required for Treg selection. Here, we used double transgenic
      mice (TCR-HA x IgHA) and followed the kinetics and phosphorylation status of HA
      specific Tregs that develop in the absence or presence of their agonist ligand
      expressed in the thymus, as well as of polyclonal "naturally occurring" Tregs
      (nTregs). We found that, in basal conditions, nTregs showed enhanced basal
      phosphorylation of c-Cbl, Erk and PI3K, indicating their selection by high
      avidity ligands. However, in response to TCR cross-linking, both nTregs from
      Balb/c mice and HA-specific Tregs showed reduced levels of phosphorylated Erk1/2,
      c-Cbl and Akt. We conclude that thymus-derived Tregs display a characteristic
      "signalling signature" that suggests qualitative differences in TCR-mediated
      signalling that may not be explained merely by a higher TCR avidity.

PMID- 19860597
TI  - Ritual behaviours of children with autism spectrum disorders in Taiwan.
AB  - BACKGROUND: Ritual behaviour, while often considered as nonpurposeful or
      problematic, can also be regarded as functional behaviour for individuals with
      autism spectrum disorders (ASD). This study investigated the types and
      characteristics of ritual behaviour in children with ASD in a Taiwan context.
      METHODS: Sixty-four primary school teachers, who taught 71 students with ASD,
      were surveyed. In addition, observations with five children with ASD were
      conducted, and their parents were interviewed. Two control groups of students
      with intellectual disability and children without a disability were included in
      the study. RESULTS: Ritual behaviour occurred in the majority of children with
      ASD, and across all levels of ability. Prevalence was much higher in the ASD
      group as compared to the two control groups. These behaviours could be
      categorised into seven types, and ritual behaviour was strongly associated with
      sensory sensitivity. CONCLUSIONS: Although ritual behaviours were diverse in
      nature and were common among children with ASD in Taiwan, their frequency may be
      associated with cultural context.

PMID- 19860598
TI  - Dispersed or clustered housing for adults with intellectual disability: a
      systematic review.
AB  - BACKGROUND: The purpose of this review was to evaluate the available research on
      the quality and costs of dispersed community-based housing when compared with
      clustered housing. METHODS: Searches against specified criteria yielded 19 papers
      based on 10 studies presenting data comparing dispersed housing with some kind of
      clustered housing (village communities, residential campuses, or clusters of
      houses). The studies reported the experience of nearly 2,500 people from four
      different countries. RESULTS: In five of eight quality of life domains there were
      no studies reporting benefits of clustered settings. In respect of interpersonal
      relations, emotional, and physical well-being, clustered settings had some
      advantages. However, in many of these cases the better results refer only to
      village communities and not to campus housing or clustered housing. In terms of
      costs, clustered housing was usually less expensive because of lower staffing
      levels. In two of the three studies that examined costs controlling for user
      characteristics, there was no statistically significant difference. CONCLUSION:
      Dispersed housing appears to be superior to clustered housing on the majority of
      quality indicators studied. The only exception to this is that village
      communities for people with less severe disabilities have some benefits; this is
      not, however, a model which can be feasibly provided for everyone. Clustered
      housing is usually less expensive than dispersed housing but this is because it
      provides fewer staff hours per person. There is no evidence that clustered
      housing can deliver the same quality of life as dispersed housing at a lower
      cost.

PMID- 19860599
TI  - Muscle strength and range of movement deficits 1 year after hip resurfacing
      surgery using posterior approach.
AB  - PURPOSE: The aim was to evaluate the effect of the posterior surgical approach on
      hip muscle strength and range of movement (ROM). METHODS: Maximal isometric
      external and internal rotator strength of the hip muscles and bilateral leg
      extension strength were measured by dynamometers. Active (AROM) and passive
      (PROM) range of motion of the hip were measured by goniometers in 30 patients
      before and 3, 6 and 12 months after hip resurfacing. Postoperatively the patients
      were advised to return to their usual physical activities. RESULTS: Prior to the
      surgery internal rotation strength was on the same level on both sides, whereas
      external rotation strength of the operated hip was 26% (p < 0.001) lower compared
      with the unoperated side. External rotation strength remained at the lowered
      level, but internal rotation strength of the operated hip increased over the
      level of the contralateral side (both p < 0.001) at 12-month follow-up leading to
      the imbalance in external/internal rotation strength ratio (p < 0.001).
      Preoperatively, all active and passive ROMs of the operated side were
      statistically lower than on the unoperated side (p < 0.001). ROMs of the operated
      hip improved significantly with the exceptions that active external rotation
      decreased after the operation (p < 0.001). CONCLUSIONS: The patients reported
      remarkable decrease in pain postoperatively. However, the surgical procedure,
      particularly the division of the external hip rotator muscles led to specific
      external rotation strength and ROM deficits. Because typical spontaneous physical
      activity could not restore hip function, there is a need for specific
      postoperative rehabilitative programs.

PMID- 19860600
TI  - Process evaluation of a trial evaluating a multidisciplinary nurse-led home
      visiting programme for vulnerable older people.
AB  - PURPOSE: This article describes the content of and adherence with a nurse-led
      home visiting programme (Dutch Geriatric Intervention Programme; DGIP) for
      vulnerable older people. The randomised Dutch EASYcare Study showed positive
      patient endpoints for DGIP. Describing content and adherence is rarely performed,
      but highly important for understanding the results of trials. METHOD: DGIP is a
      complex multicomponent intervention tailored to the patients' needs. This process
      evaluation describes these components and patient characteristics and creates
      meaningful clusters of these specific components using hierarchical cluster
      analysis. Both patient/caregiver and physician adherence rates and possible
      predictors were investigated. RESULTS: In line with the heterogeneity among the
      subjects, the individual treatment plans turned out to be highly tailored.
      Cluster analysis identified five clusters of intervention components. DGIP turned
      out to be largely unsuitable for one group of very vulnerable older participants
      in urgent need of more care. Overall, physician adherence was 75% and was better
      than patient adherence (51% complete/partial adherence). Adherence levels
      increased when both patients, caregivers and physicians received recommendations.
      CONCLUSIONS: The content of a multicomponent tailored home-visiting programme was
      very diverse, matching the heterogeneity among frail elderly subjects. Detailed
      process and cluster analysis helped to understand the content of the
      intervention, sharpen target criteria and identify possibilities to improve
      adherence.

PMID- 19860601
TI  - Health-related and subjective quality of life of older adults with visual
      impairment.
AB  - PURPOSE: To document health-related quality of life (HRQOL) and subjective
      quality of life (SQOL) and explore their correlates in older adults seeking
      services for visual impairment (VI). METHOD: A convenience sample of 64
      participants (79.3 +/- 5.9 years) with VI was interviewed at home. HRQOL was
      measured with the Visual Function Questionnaire-25 and SQOL with the Quality of
      Life Index. The potential correlates were as follows: personal factors
      (sociodemographic characteristics, co-morbidity, depressive symptoms, activity
      level), environmental factors (technical aids, social support) and participation
      in daily activities and social roles (level and satisfaction). RESULTS: Compared
      to normative data from previous studies of older adults, the participants had
      lower HRQOL but similar SQOL. Greater level of participation in social roles,
      higher perceived activity level, use of a writing aid and greater satisfaction
      with participation in social roles together explained better HRQOL (R2 = 0.66).
      Fewer depressive symptoms, greater satisfaction with participation in social
      roles and with social support and fewer co-morbidities together explained better
      SQOL (R2 = 0.70). CONCLUSIONS: HRQOL of older adults with VI is mainly explained
      by level of participation correlates, while their SQOL is mainly explained by
      depressive symptoms and satisfaction variables. The results also underscore the
      importance of social roles for HRQOL and SQOL of this population.

PMID- 19860602
TI  - Predictors of functional ambulation and patient perception following total knee
      replacement and short-term rehabilitation.
AB  - PURPOSE: To investigate whether measured and patient-perceived function 6 months
      after total knee replacement (TKR) can be predicted from factors measured during
      post-operative rehabilitation. METHOD: Retrospective analysis of data from a
      randomised clinical trial involving 100 patients after TKR. High- and low
      performing subjects for pain, WOMAC score and 6-min walk test (6MWT) at 2, 8 and
      26 weeks post-TKR were partitioned and analysed. Multiple stepwise regression
      analysis was applied to the contributing factors to determine associations with
      outcome. RESULTS: Prediction of outcome was unconvincing based upon variables
      recorded at 2 weeks; however, status at 8 weeks was a better indicator of
      functional performance and perception at 26 weeks. 6MWT at 26 weeks could be
      predicted from VAS pain scores and 6MWT at 8 weeks (r = 0.789; p < 0.001).
      Prediction of pain and patient perceived function at 26 weeks was also dependent
      on performance in 6MWT at 8 weeks (r = 0.51; p < 0.05). Males and those with
      lower body mass index values demonstrated better functional outcomes. CONCLUSION:
      Functional status at 2 weeks post-surgery gives few indicators of ultimate
      status, possibly because of pain, joint swelling and other immediate post
      operative factors. However, measurements taken at 8 weeks, following an
      outpatient-based exercise programme, provides a reasonable estimate of
      performance and response 26 weeks after surgery. Patient and clinician
      expectations for longer-term recovery could be informed by these findings.

PMID- 19860604
TI  - Successful treatment of Hodgkin lymphoma and acute leukemia.

PMID- 19860603
TI  - A phase I/II dose escalation study of apolizumab (Hu1D10) using a stepped-up
      dosing schedule in patients with chronic lymphocytic leukemia and acute leukemia.
AB  - Apolizumab (Hu1D10), a humanized monoclonal anti- Human leukocyte antigen -DR
      beta-chain antibody, mediates apoptosis of chronic lymphocytic leukemia (CLL)
      cells in vitro. We conducted a phase I/II dose-escalation study of thrice-weekly
      apolizumab (1.5, 3.0, 5.0 mg/kg/dose) for 4 weeks in relapsed CLL. Two of six
      patients at 5.0 mg/kg/dose developed treatment-related dose-limiting toxicity
      (aseptic meningitis, hemolytic uremia). Other toxicities included infusion
      toxicity, urticaria, and headache. Eleven patients were enrolled in a phase I/II
      expansion to evaluate the maximum tolerated dose (MTD) of 3.0 mg/kg/dose. In
      total, 23 patients were enrolled (22 CLL, 1 ALL). Nineteen patients with CLL were
      treated at or above the MTD. One partial response was observed, and three
      patients had stable disease exceeding 6 months. Pharmacokinetic analysis
      demonstrated a dose-dependent C(max) increase and serum antibody accumulation
      after week 1 of therapy. Given the toxicity and lack of efficacy in this and
      other trials in lymphoma and solid tumors, further development of apolizumab was
      discontinued.

PMID- 19860605
TI  - Primary myelofibrosis relapsed with duodenal myeloid sarcoma after allogeneic
      stem cell transplantation.

PMID- 19860608
TI  - Weekly treatment with a combination of bortezomib and bendamustine in relapsed or
      refractory indolent non-Hodgkin lymphoma.

PMID- 19860607
TI  - Pilot study of rituximab plus donor-lymphocyte infusion to prevent or treat
      relapse in B-cell lymphoma after allogeneic stem cell transplantation.

PMID- 19860606
TI  - Hematogones are markedly reduced in pediatric acquired aplastic anemia:
      multiparametric flow cytometric analysis.
AB  - Acquired aplastic anemia (AA) and myelodysplastic syndromes (MDS) are bone marrow
      (BM) failure syndromes with overlapping clinical features, and at least a subset
      appears to share common pathophysiologic mechanisms. Recent studies of MDS have
      shown down-regulation of genes involved in B-cell development and decreased B
      cell precursors (hematogones). We explored the possibility that AA, similar to
      MDS, might also be associated with defects in development of lymphoid cells,
      especially B-cells, by using flow cytometry to assess the presence of hematogones
      and mature lymphocytes in BM samples from 25 children with AA and 41 age-matched
      controls. We observed that the percentage of total and early (stage I)
      hematogones were significantly decreased in AA compared to controls, and they
      returned to normal numbers after hematopoietic stem-cell transplant. This
      demonstrates early B-cell lineage involvement in AA, similar to recent findings
      in MDS. Our findings suggest dysfunction of an early multilineage progenitor in
      the pathogenesis of AA.

PMID- 19860609
TI  - Antibacterial prophylaxis with levofloxacin in patients after allogeneic stem
      cell transplantation and neutrophil reconstitution: results from a double
      blinded, placebo-controlled phase III trial and overview of recent clinical
      practice.

PMID- 19860611
TI  - Is there a role for bone scan in Hodgkin lymphoma in the age of 18F
      fluorodeoxyglucose positron emission tomography?

PMID- 19860612
TI  - Random serum methotrexate determinations for assessing compliance with
      maintenance therapy for childhood acute lymphoblastic leukemia.
AB  - The cure rate for acute lymphoblastic leukemia (ALL) may exceed 85%. Up to three
      years of maintenance therapy with weekly methotrexate (MTX) and daily 6
      mercaptopurine is required. Compliance with maintenance is essential to eliminate
      the residual leukemic clone. We determined the compliance status of children with
      ALL treated at a University Hospital. The study had three phases: a direct
      structured interview, the search for lack of compliance documented in the
      clinical files, and measurement of serum MTX levels, in three random occasions,
      using a polarized fluorescent immunoassay. In 5 of 49 (10%) interviews, at least
      an episode of non-compliance was reported. In the clinical file, 8 of 49 (16.3%)
      patients referred skipping maintenance drugs. In 14 of 49 (28.6%) children, MTX
      was not present in serum in at least one measurement. Face-to-face interviews and
      clinical file notes were unreliable sources for monitoring compliance. Random
      determination of serum MTX levels should be given consideration for monitoring
      long-term compliance with maintenance therapy in children with ALL.

PMID- 19860613
TI  - The effect of homoharringtonine in patients with chronic myeloid leukemia who
      have failed or responded suboptimally to imatinib therapy.

PMID- 19860614
TI  - Disease status at autologous stem cell transplantation and the cell of origin
      phenotype are important predictors of outcome in patients with neurologic
      (central nervous system) relapse of diffuse large B-cell lymphoma undergoing
      autologous stem cell transplantation.
AB  - Neurologic relapse of systemic diffuse large B-cell lymphoma (DLBCL) is
      associated with poor outcome. The existing literature about this specific entity
      is very limited. We present a retrospective analysis of patients with
      neurological relapse of DLBCL and correlate the outcome according to the disease
      stage at autologous stem cell transplantation (ASCT) and the cell of origin
      phenotype. Totally, 11 patients with neurologic relapse of DLBCL underwent ASCT,
      seven in complete remission (CR) and four with active disease. The conditioning
      regimens included LACE (six), BEAM (two), and Bu/Mel (three). Ten patients
      relapsed after ASCT. All patients with CNS relapse died of progressive disease.
      Patients with systemic relapse were salvaged by further treatment. The median
      disease free survival (DFS) and overall survival (OS) for patients in CR at ASCT
      is far superior than those with active disease at ASCT (24 and 33 months versus 3
      and 5 months, respectively). For patients undergoing ASCT in CR, the germinal
      centre (GC) phenotype is associated with a superior DFS and OS as compared to non
      GC phenotype (36 and 40 months versus 3.5 months and 5 months, respectively).
      Patients with neurological relapse of DLBCL have a poor outcome after ASCT; the
      outcome is worse for patients with non-GC phenotype irrespective of the disease
      stage at ASCT.

PMID- 19860615
TI  - Early detection of patients with poor risk diffuse large B-cell lymphoma.
AB  - More than 60% of patients with diffuse large B-cell lymphoma (DLBCL) will be
      cured with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
      (R-CHOP). However, the outcome following secondary therapies remains poor. Early
      identification of high-risk patients would allow alternative treatment strategies
      to be considered. Clinical prognostic factors, such as the International
      Prognostic Index remain useful, but can no longer identify patients with a very
      poor outcome. Identification of molecular prognostic markers will be required to
      improve risk stratification. A large number of molecular markers have been
      reported to be prognostic in patients with DLBCL treated with CHOP, and more
      recently with R-CHOP. These markers require further validation before clinical
      utility can be established. Continuous reassessment of clinical and molecular
      markers in the context of prospective clinical trials is necessary to ensure
      ongoing relevance.

PMID- 19860616
TI  - Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell
      lymphoma.
AB  - Although the International Prognostic Index (IPI) score is a valuable prognostic
      tool in diffuse large B-cell lymphoma (DLBCL), other risk-stratifying factors may
      be of value. The aim of this study was to define the prognostic value of EBV
      expression in de novo nodal DLBCL. Seventy-four cases were selected between
      January 2002 and December 2007. Clinical data were reviewed and tissue samples
      were evaluated for expression of CD20, CD10, bcl-6, MUM1, and EBV-encoded RNA
      (EBER). Of 74 evaluated cases, 53 cases (72%) were of non-germinal center-like
      subtype and 11 cases (15%) were positive for EBER. In a univariate analysis of
      the 57 patients who received chemotherapy, factors associated with survival were
      EBV status, performance status, LDH level, and IPI score. Using a multivariate
      analysis, a prognostic model was developed using IPI score and EBV status, which
      showed statistical significance. Our study supports EBV status as a powerful
      prognostic factor in de novo nodal DLBCL. Prospective studies should be carried
      to validate this hypothesis.

PMID- 19860618
TI  - Monitoring of plasma cell proliferative and apoptotic indices in the course of
      multiple myeloma.
AB  - In a group of 310 patients with multiple myeloma (MM) we assessed the
      proliferative (PC-PI) and apoptotic indices (PC-AI). Patients were divided
      according to the disease state, i.e. at the time of diagnosis, in relapse, and in
      MM remission. We assessed the behavior of both indices with respect to therapy
      response and activity of the disease. In patients who reached remission, there
      was a significant decrease of PC-PI together with an increase of PC-AI in
      comparison with initial measurements. In non-responders, there was a reverse
      trend with increasing PC-PI and decreasing PC-AI. The values of PC-PI and PC-AI
      in residual myeloma population were similar regardless of treatment, i.e. in
      patients treated using conventional chemotherapy and after high-dosed
      chemotherapy with autologous stem cell transplant. Patients in long-lasting
      remission phase maintained stable low values of PC-PI with high PC-AI without a
      significant change, whereas in the group of progressing/relapsing patients, there
      was a significant increase of PC-PI together with a decrease of PC-AI. Our
      results suggest that longitudinal measurement of proliferative and apoptotic
      indices in MM plasmocytes helps to estimate the behavior of the tumor population
      and may thus become a convenient auxiliary parameter for prognosis and a
      targeted, individualized treatment approach.

PMID- 19860619
TI  - Autoimmune thyroiditis associated with marrow fibrosis and pancytopenia.

PMID- 19860617
TI  - Alemtuzumab for relapsed and refractory erythrodermic cutaneous T-cell lymphoma:
      a single institution experience from the Robert H. Lurie Comprehensive Cancer
      Center.
AB  - We present the results of an open-label clinical trial and the clinical use of
      alemtuzumab in 19 heavily pretreated patients with advanced erythrodermic
      cutaneous T-cell lymphomas (CTCL) (erythrodermic mycosis fungoides and Sezary
      syndrome). Ten patients received alemtuzumab intravenously using an escalating
      dose regimen with a final dose of 30 mg three times weekly for 4 weeks followed
      by subcutaneous administration for 8 weeks. Nine patients were treated with only
      the SQ or IV dosing. The overall response rate was 84%, with 9 (47%) complete and
      7 (37%) partial remissions. The median follow-up was 24 months (range, 6 to 62+
      months). Median overall survival was 41 months whereas median progression free
      survival was 6 months. Minimal residual disease by T-cell gene rearrangement
      studies was detected in 11 patients who achieved complete response and partial
      response. Toxicities included myelosuppression and infections; however, the
      majority of side effects were of Grade 2 in severity and transient. One patient
      was diagnosed with a concurrent lymphoma (mantle cell lymphoma) 6 months after
      completing alemtuzumab therapy. Alemtuzumab is particularly effective in patients
      with erythrodermic CTCL with acceptable toxicities. Combined strategies with
      alemtuzumab may achieve molecular remissions with longer response durations.

PMID- 19860620
TI  - Is inactivation of O6-methylguanine DNA methyltransferase still a favorable
      prognostic factor of patients with diffuse large B-cell lymphoma in the era of R
      CHOP chemotherapy?
AB  - The prognostic significance of O6-methylguanine DNA methyltransferase (MGMT)
      inactivation was evaluated in patients with diffuse large B-cell lymphoma (DLBCL)
      who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in
      addition to rituximab. In this retrospective study, we used the methylation
      specific polymerase chain reaction to investigate MGMT promoter methylation
      status and immunohistochemistry to evaluate MGMT expression in patients with
      DLBCL who received rituximab plus CHOP (R-CHOP) chemotherapy. No difference in
      patient characteristics, disease characteristics, response, or survival in
      patients with DLBCL who received front-line R-CHOP chemotherapy was observed
      according to MGMT methylation status and MGMT expression. On multivariate
      analysis, Grade 3-4 mucositis in the MGMT methylated group was significantly
      higher than that in the MGMT unmethylated group (hazard ratio (HR) 2.40, 95% CIs:
      1.26-7.26, p = 0.014). This study demonstrated that inactivation of MGMT does not
      appear to play an important role in patients with DLBCL who received R-CHOP
      chemotherapy either with regard to the response rate or overall survival.
      Additionally, Grade 3-4 mucositis was found to be significantly related with
      inactivation of MGMT by a multivariate analysis.

PMID- 19860621
TI  - Efficacy of the BEACOPP regimen in refractory and relapsed Hodgkin lymphoma.
AB  - The BEACOPP regimen is a consolidated first-line treatment regimen for advanced
      stage Hodgkin lymphoma (HL), while few data are available on the efficacy of this
      regimen in advanced disease. About 50% of patients with HL relapsed after or
      refractory to first-line therapy achieve a durable response after peripheral
      blood stem cell transplantation (PBSCT). Patients relapsing after a PBSCT
      (performed as second line therapy) have a very poor prognosis. We evaluated the
      efficacy of BEACOPP in two settings: patients refractory or in relapse after
      first-line therapy (Group A) and patients relapsing after a PBSCT (Group B).
      Twenty-three patients with HL, admitted between February 2003 and April 2007,
      were retrospectively studied: 10 patients in Group A and 13 in Group B. Group A:
      Nine complete remissions (CR) and one partial remission (PR) were achieved
      following BEACOPP treatment. After a median follow-up of 32 months, one patient
      has died due to secondary leukemia, while the other eight are alive, five (50%)
      in second CR, three in third CR after PBSCT and one with disease. Group B: Eight
      of the 13 patients (62%) obtained a CR, one patient a PR, two were refractory and
      two have died of toxicity. To date, eight patients (62%) are alive, four (31%)
      still in CR. All patients experienced hematologic toxicity (WHO 3-4) with two
      deaths due to septic shock. These results show that BEACOPP is an effective
      regimen for both refractory/relapsed patients with HL after first-line treatment
      (Group A) and for patients relapsing after a PBSCT (Group B) with a 3-year
      probability of overall survival, progression-free survival, and cumulative
      incidence of relapse of 90, 50, and 33.3% in Group A, and 61, 31, and 37.5% in
      Group B, respectively.

PMID- 19860622
TI  - Comeback for the camptothecins?

PMID- 19860623
TI  - Indirubin derivatives inhibit malignant lymphoid cell proliferation.
AB  - Indirubin-3'-monoxime (IO) is a derivative of indirubin, an active compound of a
      traditional Chinese medicinal recipe used to treat various inflammatory and
      malignant diseases. The main in vitro targets of IO (i.e. cyclin dependent
      kinases, glycogen synthase kinase-3beta, Stat 3 and Aryl hydrocarbon receptor)
      are regulators of lymphocyte activation. We investigated the interest of IO and
      its derivative 6-bromo-indirubin-3'oxime (6BIO) for inhibiting the growth of
      malignant lymphoid cells. IO (1-20 microM) induced cell cycle inhibition and cell
      death in malignant B- (IM9, Reh6) and T- (Jurkat, CEM-T) lymphoid cell lines
      depending to cell type, doses, and duration of treatment. IO and 6BIO (10 microM)
      treatment for 24 and 48 h were compared: 6BIO treatment resulted in a stronger
      cytotoxicity and more profound inhibition of cell proliferation. Taken together,
      these results showed that IO and, moreover, its derivative 6BIO may be potent
      antiproliferative agents in malignant lymphoid cells.

PMID- 19860625
TI  - Lysophosphatidic acid receptor expression in chronic lymphocytic leukemia leads
      to cell survival mediated though vascular endothelial growth factor expression.
AB  - Lysophosphatidic acid (LPA) protects chronic lymphocytic leukemia (CLL) cells
      from apoptosis. Vascular endothelial growth factor (VEGF) also protects CLL cells
      against apoptosis. The mechanism for LPA protection against apoptosis in CLL
      cells is unknown. Herein, we show CLL cells express LPA receptors LPA(1-5) but in
      normal B cells, LPA(1) was rarely expressed and LPA(3,) LPA(4,) and LPA(6) were
      undetectable whereas the other LPA receptors were expressed. LPA plasma levels
      are similar in patients with CLL compared to healthy controls. In contrast,
      plasma levels of VEGF are elevated in patients with CLL compared to healthy
      controls and LPA treatment induced VEGF secretion in CLL cells. CLL cells also
      express VEGF receptors and LPA protection against Flu induced apoptosis is
      blocked by inhibition of VEGF receptor activation. These results indicate that
      LPA protects CLL cells from apoptosis through higher expression of LPA receptors
      and autocrine production of VEGF.

PMID- 19860624
TI  - Effects of motexafin gadolinium in a phase II trial in refractory chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) cells are susceptible to oxidative stress. The
      expanded porphyrin, motexafin gadolinium (MGd), reacts with intracellular
      reducing metabolites and protein thiols to generate reactive oxygen species
      (ROS). A phase II trial administered MGd 5 mg/kg/day IV for 5 days every 3 weeks
      until disease progression to patients with previously treated CLL and small
      lymphocytic lymphoma. Thirteen patients (median age 66 years) with a median of
      four prior therapies (range 2-9) were enrolled. Modest anti-tumor activity was
      seen in three patients, with improvement in lymphocytosis, lymphadenopathy and/or
      splenomegaly, but no patient achieved a partial or complete response by NCI 96
      criteria. Flow cytometry confirmed tumor uptake of MGd. Serial increase in AKT
      phosphorylation in patient samples following MGd treatment was not observed,
      suggesting intracellular generation of ROS was not optimal. Therefore, this
      schedule of administration achieved MGd uptake into primary tumor cells in vivo,
      but clinical activity was modest.

PMID- 19860626
TI  - Predictors of outcome in post-transplant lymphoproliferative disorder: an
      evaluation of tumor infiltrating lymphocytes in the context of clinical factors.
AB  - We hypothesized that the number of tumor infiltrating cytotoxic T-cells (CTCs)
      and regulatory T-cells (Tregs), shown to have prognostic value in other
      lymphoproliferative disorders, could predict survival in post-transplant
      lymphoproliferative disorder (PTLD). Sixty-two patients were diagnosed with PTLD
      between 1987 and 2007, with 44 cases representing monomorphic B-cell PTLDs with
      diffuse aggressive morphologic features. Of these 44 cases, 31 had sufficient
      tissue for further study. On univariate analysis, high tumor infiltrating CD3(+)
      T-cell (> or =550/10 hpf) and TIA-1(+) CTC (> or =300/10 hpf) counts were
      associated with favorable overall survival (OS), PTLD-specific survival (PTLD
      SS), and progression-free survival (PFS) while Treg counts were not predictive of
      outcome. However, on multivariate analysis, clinical factors were the most
      powerful predictor of PTLD outcome (performance status and CHOP as first line
      therapy for OS; performance status and number of extranodal sites for both PTLD
      SS and PFS).

PMID- 19860627
TI  - Analysis of prognostic factors in peripheral T-cell lymphoma: prognostic value of
      serum albumin and mediastinal lymphadenopathy.
AB  - We evaluated multiple patient characteristics for their prognostic significance
      in patients with peripheral T-cell lymphoma (angioimmunoblastic T-cell lymphoma
      [AITL; n = 31] and peripheral T-cell lymphoma, not otherwise unspecified [PTCL
      NOS; n = 37]). Five-year overall survival (OS) rates in AITL and PTCL-NOS were
      49% and 45%, respectively (p = 0.89). Cox proportional hazard model revealed that
      male sex, hemoglobin <10.0 g/dL and performance status (PS) > or =2 were
      independently associated with shorter OS in AITL. In patients with PTCL-NOS, low
      albumin, PS > or = 2, and mediastinal lymphadenopathy were independently
      associated with worse OS. When analysis in PTCL-NOS was performed incorporating
      Prognostic Index for PTCLu (PIT), low albumin and mediastinal lymphadenopathy
      were still both prognostic for OS. Three-year progression free survival (PFS)
      rates in AITL and PTCL-NOS were 49% and 47%, respectively (p = 0.578). None of
      the parameters was significantly associated with shorter PFS in AITL. In patients
      with PTCL-NOS, PS > or = 2 and mediastinal lymphadenopathy were independently
      associated with shorter PFS. The result is in keeping with previous large scale
      studies. Besides, we showed the potential prognostic importance of albumin and
      mediastinal lymphadenopathy in patients with PTCL-NOS.

PMID- 19860628
TI  - Mitoxantrone and etoposide in patients with newly diagnosed acute myeloid
      leukemia with persistent leukemia after a course of therapy with cytarabine and
      idarubicin.
AB  - The most effective regimen for patients with acute myeloid leukemia (AML) who do
      not achieve complete remission (CR) after one course of cytarabine and an
      anthracycline has not been extensively studied. We evaluated retrospectively the
      efficacy, toxicity, and prognostic factors for the achievement of CR following
      mitoxantrone and etoposide in 74 patients with newly diagnosed AML who did not
      respond to one course of therapy with cytarabine and idarubicin. CR was achieved
      in 39% of patients; 14% died of infectious complications; no grade 3 or 4 hepatic
      toxicities were observed. Median duration of overall survival was 9.0 months (95%
      CI 5.8-14.9 months). The median duration of relapse-free survival was 11.0 months
      (95% CI: 9.0-19.3 months). A lower CR rate was associated with unfavorable risk
      status at diagnosis and higher percent blasts. Our data suggest that the
      combination of etoposide and mitoxantrone is an effective second-course therapy
      in patients with newly diagnosed AML.

PMID- 19860629
TI  - Primary bone lymphoma--the University of Miami experience.
AB  - Primary bone lymphoma (PBL) is a rare disease. There has been paucity of studies
      addressing its therapy and prognosis. We retrospectively examined PBL cases seen
      at the University of Miami from June 2000 to August 2007 to describe our single
      institution experience and review the literature. Fifty-three patients were
      identified with a median age of 52 (18-87) and a median follow-up of 40 months (0
      106). The most common histologic type was diffuse large B-cell lymphoma (83%).
      Forty-one patients (77%) presented with localized disease and 48 were treated at
      our institution. Forty-six patients underwent chemotherapy (40 patients) and/or
      radiation (36 patients). Forty-four patients achieved a complete response and all
      patients were alive at last follow-up. The progression-free survival (PFS) was
      83% at 4 years. No difference in PFS was observed between patients treated with
      chemotherapy or combined chemotherapy plus radiation. There was a trend toward
      improvement in PFS (p = 0.062) of patients with DLBCL treated with rituximab plus
      chemotherapy. Our single institutional experience demonstrates that the outcome
      of patients with PBL is excellent. Although the current data support the use of
      combined modality treatment for localized PBL, randomized controlled trials are
      needed especially now, when rituximab is routinely added to chemotherapy
      regimens.

PMID- 19860630
TI  - [Differential diagnosis in cervical lymphadenopathies: efficacy of B-mode, color
      and power Doppler ultrasonography].
AB  - OBJECTIVES: Our purpose was to investigate cervical lymphadenopathies by using
      color Doppler spectral analysis and power Doppler ultrasonography methods as well
      as B-mode ultrasound and to classify them as malignant or benign lesions and to
      compare the results with the histopathological findings. PATIENTS AND METHODS:
      Sixty-nine lymph nodes of 69 patients were evaluated with color and power Doppler
      ultrasonography as well as B-mode ultrasonography. The shape and dimensions of
      the lymph nodes were assessed with B-mode ultrasonography; their vascularization
      pattern with power Doppler sonography and with color Doppler spectral analysis.
      Vascular pattern was evaluated according to the vascularization of the lymph
      node. Vascular resistive index and pulsatility index were assessed by at least
      three flow samplings. We measured resistive index, pulsatility index, peak
      systolic velocity, and end diastolic velocity. Results of Doppler analysis were
      compared with clinical findings and histopathologic results. Nodes were grouped
      as metastasis, lymphoma, tuberculosis, and reactive benign lymphadenopathies with
      respect to ultrasonographic results. RESULTS: Forty-four of 69 lymph nodes were
      found to be malignant histopathologically. In color Doppler analysis, most malign
      metastatic lymphadenopathies showed peripheral (76.4%), and the rest of them
      (23.6%) showed peripheral and hilar (mix) vascularization. Most benign
      lymphadenopathies (88%) and lymphomatous lymphadenopathies (85%) had hilar
      vascularization. In tuberculous lymphadenopathies, 50% of them showed avascular
      pattern and the rest of them had variable type of vascularization. A resistive
      index = or > 0.7 indicated a malignant metastatic lymphadenopathy and a resistive
      index <0.5 was consistent with benign lesions. In lymphomatous and tuberculous
      lymphadenopathies resistive index values were between 0.6-0.7. The sensitivity of
      the resistive index for distinguishing inflammatory from neoplastic
      lymphadenopathies was 84.6%, the specificity 100% and the diagnostic accuracy
      95.7% (p<0.001). CONCLUSION: In addition to B-mode ultrasonography findings,
      vascularity pattern assessment and spectral analytical measurements with color
      and power Doppler ultrasonography has an important contribution for the
      differential diagnosis of cervical lympadenopathies.

PMID- 19860631
TI  - [The comparison of the expansion of polyps according to the Ki-67 and computed
      tomography scores].
AB  - OBJECTIVES: The disease extention in nasal polyps was compared by using the
      mitotic activity rates and the computed tomography scores. PATIENTS AND METHODS:
      This study was conducted on 19 nasal polyposis patients (8 males, 11 females;
      mean age 40.0+/-13.7 years; range 20 to 63 years). The preoperative computed
      tomography records of the patients were evaluated according to the Lund-Mackay
      grading system. The polyp tissues of the same patients were stained with the Ki
      67 antigen for immunohistochemical evaluation. The correlation between the
      radiologic results and the Ki-67 values was compared by means of the Spearman's
      correlation test. RESULTS: The mean computed tomography score was observed as
      14.3+/-4.7 (range 7-24). The mean Ki-67 score resulting from the
      immunohistochemical staining was calculated as 24.3+/-18.5 (range 3.3-73.5%). A
      significant correlation was determined between the Ki-67 values and the computed
      tomography scores. ("Spearman's" correlation factor: 0.677; p<0.001). CONCLUSION:
      As the mitotic activity rate of nasal polyps increases, both the volume of the
      polyps and the computed tomography scores increase as a result of the blockage of
      the sinus ostiums by the increased polyp volume.

PMID- 19860632
TI  - Preoperative evaluation of chronic rhinosinusitis patients by conventional
      radiographies, computed tomography and nasal endoscopy.
AB  - OBJECTIVES: The aim of this study was to compare the efficacy of conventional
      radiography (CR), computed tomography (CT) and nasal endoscopy for the
      preoperative evaluation of chronic rhinosinusitis in patients with persistent
      complaints despite appropriate medical therapy. PATIENTS AND METHODS: Forty-three
      patients (26 males, 17 females; mean age 43 years; range 15 to 73 years) were
      prospectively evaluated. All patients underwent detailed physical examination, CR
      and coronal high resolution CT of paranasal sinuses. Thirty of them were
      evaluated with detailed nasal rigid and/or flexible endoscopy as well. The
      anatomic variations and mucosal changes in paranasal sinuses were noted. The
      specificity and sensitivity of CR was calculated using CT findings as a reference
      point. Surgery was performed on two of the other three patients because of
      obstructive symptoms of middle turbinate. Paradoxal middle turbinate surgery was
      performed on one patient due to a headache of rhinogenic origin. RESULTS: In our
      study 40 (93%) of all patients showed mucosal abnormalities on CT. Computed
      tomography scanning of the patients revealed anatomic variations in 74.4% of the
      cases. Mucosal pathology was most frequently observed in the anterior ethmoid
      region (middle meatus). While we found mucosal anomalies in 47.4% of all sinuses
      using CR, 42.2% of these cases were confirmed with CT. Also, 19.5% of all sinuses
      evaluated as normal with CR presented pathologic findings on CT. An overall
      correlation of 75.3% was observed between CR and CT, while diagnostic nasal
      endoscopy and CT findings were correlated at a rate of 87%. CONCLUSION: (i) While
      no ipsilateral maxillary or frontal sinus disease was detected when no
      abnormality in the anterior ethmoid region and infundibulum was observed
      endoscopically in the presence of mucosal abnormalities similar abnormalities
      were seen at the same side for maxillary or frontal sinuses. (ii) Anatomic
      variations of nasal and paranasal sinuses may be considered as etiologic and
      predisposing factors of chronic rhinosinusitis. (iii) Conventional radiography
      should not be used as a single diagnostic tool in preoperative evaluation;
      however, due to its high sensitivity, CR technique may be used alone in the
      diagnosis and follow-up of maxillary sinus disease. (iv) Nasal endoscopy may
      reduce unnecessary diagnostic CT scanning procedures.

PMID- 19860633
TI  - [The therapeutic role and effectiveness of selective neck dissection in the
      management of N0 neck].
AB  - OBJECTIVES: To assess the therapeutic role and the effectiveness of the selective
      neck dissection in the management of the clinically node negative neck in the
      head and neck squamous cell carcinomas. PATIENTS AND METHODS: The charts of 177
      patients with squamous cell carcinoma, who underwent neck dissection between
      January 2000 and January 2007, were reviewed retrospectively. Seventy neck
      dissections in 58 patients (51 males, 7 females; mean age 63 years; range 21 to
      85 years) in whom the primary site of the lesion was the larynx, oral cavity,
      oropharynx and hypopharynx, and who were considered to have N0 neck and to comply
      with the study criteria were included in the study. Details were collected on
      tumor site and stage, type of surgery, pathologic N stage, number and size of
      pathologic nodes, extracapsular spread of nodes, postoperative radiotherapy,
      local recurrence, follow up time and survival status in all patients. RESULTS: It
      was found out that selective neck dissection operations were performed on 99 of
      102 N0 patients. The follow up time was approximately 23 months in 58 patients
      who were found to comply with the inclusion criteria. The most frequent site for
      primary tumor was larynx and most patients were at T2 stage. Nine patients had
      pathologically positive lymph node with occult metastasis rate of 13%. The
      overall recurrence rate was 19%. Postoperative radiotherapy was used as adjuvant
      therapy in 15 patients. Regional control rate was lower in patients with
      pathologically positive lymph nodes. However, it was not statistically
      significant. CONCLUSION: Selective neck dissection is an effective and safe
      method for controlling and staging of the patients with clinically N0 neck.

PMID- 19860634
TI  - Effectiveness of voice therapy in hyperfunctional dysphonia in adult patients.
AB  - OBJECTIVES: In this retrospective study, voice therapy results of adult patients
      with hyperfunctional voice disorders were discussed. PATIENTS AND METHODS: Ninety
      one adult patients (59 females, 32 males; mean age: 37 years; range 18 to 54
      years) who completed their voice therapy sessions between May 2002 and May 2007
      were included in this study. The voice therapy plan was focused on developing
      competence in perception, tonus regulation, physiological breathing and
      physiological use of voice. Especially Koblenzer, Smith, Froschels, Holler
      Zangenfeind and Pahn techniques were included in the plan. Patients had voice
      therapy sessions every one or two weeks for about 30-45 minutes. On average,
      patients had eight sessions. Voice therapy was conducted by the same voice
      therapy team to the patients. Vocal use and hygiene guidelines were also
      explained to the patients. In the objective and subjective evaluation of voice,
      dysphonia severity index (DSI) and voice handicap index (VHI) scores were used
      respectively. RESULTS: After voice therapy, DSI increased from -1.4 to 1.1 and
      VHI decreased from 72 to 43. Voice therapy was found to be successful clinically.
      CONCLUSION: These results suggest that patients with hyperfunctional voice
      disorder benefits from voice therapy.

PMID- 19860635
TI  - Tonsillolithiasis with actinomycotic infection: a case report.
AB  - Tonsillar calcifications, tonsilloliths, are not rare conditions for routine ear
      nose throat examinations. Their size vary from barely visible to the pea size and
      they should be kept in mind in the differential diagnoses of radiopaque lesions
      in this region. We report a 42-year-old male patient who had a large tonsillolith
      together with an actinomycotic infection of tonsillar region. The patient
      complained about recurrent tonsillar infections. In his routine ear nose throat
      examination a large tonsillolith, lodged in the right palatine tonsil, was
      observed. The patient underwent tonsillectomy under general anesthesia.
      Histopathologic evaluation confirmed the diagnosis of tonsillolith.
      Interestingly, actinomycotic infection was observed. The pathogenesis of
      tonsilloliths is not completely defined. Many investigators have suggested that
      tonsilolliths originate as a result of recurrent tonsillar infections. Our
      purpose is to remind the tonsillolith in the differential diagnoses of chronic
      tonsillar region pathologies.

PMID- 19860636
TI  - [Lipoma of the cerebellopontine angle: two cases report and review of
      literature].
AB  - Here we report two cases with cerebellopontine angle lipoma. Cerebellopontine
      angle lipomas previously reported in the literature were reviewed. The review of
      the literature revealed the condition is more prevalent in women. The median
      tumor size was 10.26 (range: 1 to 26) mm. It was noted that these tumors are most
      frequently associated with hearing loss (56%) and tinnitus (40%), while 9%
      demonstrate no symptoms. Fifty-six percent of these patients had been operated,
      however complete resection had been accomplished in only 36% of patients. In our
      cases, the tumor sizes were 7 x 4 and 5 x 3 mm. Tinnitus and ear fullness were
      major complaints in both cases. One case had hearing loss and vertigo in addition
      to these complaints. Surgery was not performed for these cases. The patients have
      been followed up using same approach without any complication. Histopathological
      diagnosis is rarely necessary with the widespread use of magnetic resonance
      imaging. Because of the potential for significant morbidity with resection of
      these lesions, conservative follow-up is the best approach for cerebellopontine
      angle lipoma.

PMID- 19860637
TI  - A rare vascular tumor of the external auditory canal: the capillary hemangioma.
AB  - A 32-year-old woman presented to our department with a 10-month history of right
      sided intermittant otorrhagia. There was no history of hearing loss or pulsatile
      tinnitus. Otomicroscopic examination revealed a reddish mass arising from the
      right antero-superior portion of bony canal wall, which measured about 1 cm in
      diameter. The tympanic membrane seemed to be uninvolved. A computed tomography
      scan of the temporal bone showed 0.6 x 0.8 cm diameter soft-tissue mass arising
      from the right external auditory canal, 0.5 cm away from tympanic membrane. The
      lesion was excised via a transcanal approach under local anesthesia. The
      histopathologic assessment indicated a capillary hemangioma. There was no
      recurrence four years after the surgery. Hemangioma of the external auditory
      canal is a rare otologic entity. It is commonly classified as capillary or
      cavernous hemangioma. According to the literature, this case represents the
      second patient with capillary hemangioma of the external auditory canal.

PMID- 19860638
TI  - An unusual giant subacute necrotizing sialadenitis as an emergency case of
      otolaryngology.
AB  - Subacute necrotizing sialadenitis is an inflammatory necrotizing lesion occurring
      in minor salivary glands. Most cases occur in the palatal region. In this
      article, we reported a 36-year-old man referred to our clinic as an emergency
      with the complaints of excessive bleeding, airway obstruction and hipovolemia.
      Intraorally, there was a hemorrhagic, protruding giant mass in the palatal
      region. Following the first biopsy, which was not diagnostic, a second biopsy was
      performed. Histopathologic examination showed acinar cell necrosis and dense
      inflammation of the affected minor salivary glands in the second biopsy. The
      diagnosis of subacute necrotizing sialadenitis was made on the basis of clinical
      and histologic features of the lesion. Subacute necrotizing sialadenitis is a
      rare lesion, and admittance to the otolaryngology clinic as an emergency case is
      much rarer. To avoid unnecessary surgical intervention, it is necessary to
      diagnose subacute necrotizing sialadenitis correctly, which can be confused with
      malignant diseases of the salivary glands.

PMID- 19860639
TI  - [Infraorbitally located tuberculous lypmhadenitis: a case report].
AB  - Tuberculosis, which is one of the oldest diseases of the human kind, is again
      becoming an important health issue in recent years. Although mostly seen in
      lungs, it can also be localized in the lymph nodes, skin, meninges, spleen,
      surrenal tissues, which is referred to as extrapulmonary forms of tuberculosis.
      Tuberculous lymphadenitis is the most common clinical form of extrapulmonary
      tuberculosis and it is generally localized in cervical lymph nodes. A 50-year-old
      female patient presented with a hard fixed mass originating from medial canthus
      ending at nasolabial sulcus. In the magnetic resonance imaging examination, a
      solid contrast enhancing mass 20 x 18 x 15 mm in size, which was isointensely
      monitored with muscular structures in T1 based visuals and hyperintense in T2
      sequences, was seen. The mass was excised under general anesthesia and
      histopathological examination revealed tuberculous lymphadenitis. Thus, the case
      is discussed according to literature and shows us that tuberculosis may be the
      reason for lymphadenitis in the areas out of the cervical region and it should
      always be kept in mind in the differential diagnosis.

PMID- 19860640
TI  - Special Board Members Issue.

PMID- 19860641
TI  - A multi-targeted approach for a complex multifaceted disease.

PMID- 19860642
TI  - Targeting sarcomas: novel biological agents and future perspectives.
AB  - Sarcomas are a group of heterogeneous tumors that arise from mesenchymal tissue
      and account for approximately 1% of all adult solid malignancies diagnosed,
      although its incidence approaches 20% in pediatric cancers. Characterization of
      molecular abnormalities in patients with sarcomas, in particular the up
      regulation of the receptor tyrosine kinase and the PI3K-AKT-mTOR pathway, loss or
      deletions of retinoblastoma (Rb) and p53 gene, increased VEGF expression and
      angiogenesis, dysregulation of apoptosis through Bcl-2 overexpression, along with
      oncogene mutations and activations, such as c-KIT in Gastrointestinal stromal
      tumors (GISTs), makes treatment with novel biological therapies a promising
      option. This review focuses on the molecular heterogeneity of soft tissue and
      bone sarcomas, novel biological therapies currently in clinical trials to target
      the various molecular pathways, and the potential biological agents in pre
      clinical and early clinical development.

PMID- 19860643
TI  - Inflammatory systemic biomarkers in setting acute coronary syndromes--effects of
      the diurnal variation.
AB  - Clinicians have used additional tools to aid clinical assessment and to enhance
      their ability to identify the "vulnerable" patient at risk for cardiovascular
      diseases. Circulating biomarkers are one such tool used for identifying better
      high-risk individuals and to prognosticate effectively and treat patients with
      disease. A persistent immune activation is a main feature of atherosclerosis. The
      inflammatory activity is not only detectable in the vascular wall, but also in
      peripheral blood. Patients with coronary artery disease show increased numbers of
      neutrophils and T cells as well as elevated levels of several inflammatory
      mediators. On the other hand, several cardiovascular disease states show a daily
      cycle of activity, i.e. a peak incidence of cerebrovascular and cardiovascular
      events has been documented in the early morning hours. Several studies have shown
      diurnal variations in inflammatory systemic markers in patients with acute
      coronary syndrome. Diurnal variations can alter the analysis of blood-derived
      samples. Prior to the analysis of a blood sample, multiple steps are necessary to
      generate the desired specimen. The knowledge of diurnal variations is a
      prerequisite to understand and control their impact. This brief review comments
      the effect of the diurnal variation on the most important inflammatory systemic
      biomarkers in the setting acute coronary syndrome: interleukin-6, neopterin,
      matrix metalloproteinases, vascular cell adhesion molecule-1, intercellular
      adhesion molecule-1, soluble CD40 ligand, and C-reactive protein.

PMID- 19860644
TI  - The paradox of caffeine-zolpidem interaction: a network analysis.
AB  - A widely prescribed and potent short-acting hypnotic, zolpidem has become the
      mainstay for the treatment of middle-of-the-night sleeplessness. It is expected
      to be antagonized by caffeine. Paradoxically, in some cases caffeine appears to
      slightly enhance zolpidem sedation. The pharmacokinetic and pharmacodynamic
      nature of this odd effect remains unexplored. The purpose of this study is to
      reproduce a hypothetical molecular network recruited by caffeine when co
      administered with zolpidem using Ingenuity Pathway Analysis. Thus generated,
      network drew attention to several possible contributors to caffeine sedation,
      such as tachykinin precursor 1, cannabinoid, and GABA receptors. The present
      overview is centered on the possibility that caffeine potentiation of zolpidem
      sedation does not involve a centralized interaction of specific
      neurotransmitters, but rather is contributed by its antioxidant capacity. It is
      proposed that by modifying the cellular redox state, caffeine ultimately reduces
      the pool of reactive oxygen species, thereby increasing the bioavailability of
      endogenous melatonin for interaction with zolpidem. This side effect of caffeine
      encourages further studies of multiple antioxidants as an attractive way to
      potentially increasing somnolence.

PMID- 19860645
TI  - Down with the erythropoietin. Long live the erythropoietin!
AB  - In recent years the use of erythropoietin has exploded, and the anaemia of
      patients with chronic renal failure has been practically resolved with the
      administration of rHuEpo (recombinant human, Erythropoietin). However, as a
      result of an intense commercial campaign, strong therapies with this growth
      hormone, prescribed to achieve surprising sporting performances, got athletes to
      run the risk of thrombosis and vascular accidents because of red blood cells
      increase. Erythropoietin represents a significant subject of research. In fact,
      besides the ability of stimulating erythrocyte production, it has many
      pleiotropic effects. Several studies allow the assertion that EPO, in different
      concentrations, has protective effects mainly on central nervous system and
      cardiovascular system through various mechanisms, among which a key role seems to
      be held by the ability to stimulate angiogenesis. The consequent problem is that
      anaemia therapy with rHuEpo in patients with cancer may accelerate the
      progression of neoplastic disease by promoting tumour angiogenesis and, thus,
      metastasization. The study of angiogenic process in tumours led to the synthesis
      of drugs that, blocking VEGF, exert an anti-angiogenic action, contrasting cancer
      spread. However, benefits are relatively modest. Is erythropoietin perhaps the
      further angiogenic hormone to block in tumour pathology? Therefore, Epo plays a
      role in Regenerative Medicine since it intervenes in a persistent natural
      regenerative activity of humans: angiogenesis. The understanding of the
      regeneration mechanisms of complex structures in the adult salamander has opened
      original lines of research. Regenerative Medicine tries to develop therapeutic
      pathways through the stimulation of natural regenerative processes in humans.

PMID- 19860646
TI  - Antiviral agents for influenza: molecular targets, concerns of resistance, and
      new treatment options.
AB  - As resistance of influenza viruses to antiviral agents continues to evolve, new
      issues arise concerning appropriate therapy and novel therapeutic means that
      target influenza infections. Emergence of novel influenza mutations may lead to
      phenotypic as well as clinical resistance that may become a problem in serious
      influenza cases. Moreover, crucial public health issues emerge such as
      appropriate antiviral stockpiling for prepandemic and pandemic phases. The use of
      antiviral agents against seasonal, avian, and pandemic influenza should be an
      integral part of current pandemic preparedness planning and should be based on
      local and international surveillance data on antiviral resistance. As we tackle
      such resistance issues there appears to be an urgent need for developing
      strategies to conserve current antivirals against influenza, develop new agents
      or formulations that will exploit current pharmacokinetic knowledge, and study
      combination regimens.

PMID- 19860647
TI  - Gene therapy continues to make progress: clinical and regulatory perspectives.

PMID- 19860648
TI  - Progress towards liver and lung-directed gene therapy with helper-dependent
      adenoviral vectors.
AB  - Helper-dependent adenoviral vectors (HDAd) have several characteristics making
      them very attractive for human gene therapy. These vectors are completely devoid
      of viral coding sequences and are able to mediate high efficiency transduction in
      vivo to direct high level transgene expression with negligible chronic toxicity.
      Progress towards liver and lung directed gene therapy with HDAd as well as the
      current obstacles facing human applications and possible strategies to overcome
      these obstacles are discussed.

PMID- 19860650
TI  - Adenovirus mediated herpes simplex virus-thymidine kinase/ganciclovir gene
      therapy for resectable malignant glioma.
AB  - With the introduction of sophisticated tools of molecular biology, prodrug
      activating gene therapies have evolved as a novel therapeutic option for high
      grade malignant gliomas. Herpes simplex virus thymidine kinase/ganciclovir (HSV
      tk/GCV) is an extensively studied form of cytotoxic gene therapies. It is
      especially applicable for localized cancers, such as malignant glioma because of
      its restricted anatomical location and absence of metastasis. The early successes
      in the treatment of experimental malignant gliomas in the 1990s, gave impetus to
      further test this approach in this devastating disease. In malignant glioma, the
      recurrence after conventional therapy is inevitable, due to the residual cells in
      the tumor bed. The fascinating feature of adenoviral HSV-tk is that it attacks
      the residual dividing tumor cells without affecting the non-dividing neurons and
      furthermore, exploits them to destroy the malignant cells via so-called bystander
      effect. Clinical Phase I and II studies have shown significant survival advantage
      and excellent safety profile when compared to conventional treatments. Thus, the
      adenoviral mediated HSV-tk gene therapy is a promising new adjuvant treatment for
      patients with operable high-grade glioma.

PMID- 19860652
TI  - Gene therapy for neurological disorders: challenges and future prospects for the
      use of growth factors for the treatment of Parkinson's disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) family of ligands (GDFLs) as
      well as other trophic factors have, in animal models of Parkinson's disease (PD),
      demonstrated the potential for excellent ameliorative properties. Clinical trials
      that have mechanically injected GDNF intracerebrally, while demonstrating
      relative safety, have been clinically disappointing to date. Likewise,
      recombinant adeno-associated virus (rAAV) delivered neurturin (cere-120) has also
      been demonstrated to be safe in humans, however clinical results have been
      negative. The failure of the major clinical trials has cast some doubt in the
      field about trophic factor delivery for the treatment of PD. In this review, we
      make the case that GDFLs are likely to function only when there are remaining
      dopamine neurons in the nigrostriatal pathway as opposed to other candidate modes
      of action. Thus, it is our view that utilizing earlier stage PD patients who have
      significant nigrostriatal dopamine innervation remaining would be more ideal to
      demonstrate the efficacy of GDFLs. This is particularly true when considering a
      novel delivery method such as gene transfer. However, if earlier stage patients
      are to be enrolled in GDFL gene transfer trials, then a much better safety
      profile must be demonstrated by preclinical experiments. One important safety
      advance might be the use of an external regulation system to control the
      expression level of the transgene. However, gene regulation systems pose unique
      safety issues and we will discuss these in detail. It is our view that GDFLs
      still remain as a promising therapeutic approach for PD.

PMID- 19860651
TI  - Uncertainty in the translation of preclinical experiments to clinical trials. Why
      do most phase III clinical trials fail?
AB  - A large majority of Phase III, large scale, clinical trials will fail, including
      gene therapy trials. This paper attempts to address some of the causes that may
      have inadvertently led to such a high failure rate. After briefly reviewing the
      detailed and high quality work that goes both into the preparation and conduct of
      such large Phase III clinical trials, and the preclinical science that is used to
      support and originate such trials, this paper proposes a novel approach to
      translational medicine which would increase the predictability of success of
      Phase III clinical trials. We propose that a likely cause of such failures is the
      lack of "robustness" in the preclinical science underpinning the Phase I/II and
      III clinical trials. Robustness is defined as stability/reproducibility in the
      face of challenges. Many times preclinical experiments are tested in a very
      narrow set of experimental conditions. Thus, when such approaches are finally
      tested in the context of human disease, the challenge provided by the varied age
      of patients, the complex genetic makeup of human populations, and the
      complexities of the diseases to be treated provide challenges which were never
      tested or modeled. We believe that the introduction of revised approaches to
      preclinical science, including the use of the latest developments in statistical,
      scientific, mathematical, and biological models, ought to lead to more robust
      preclinical experimentation with its subsequent translation, to more robust Phase
      III clinical trials.

PMID- 19860649
TI  - "Buy one get one free": armed viruses for the treatment of cancer cells and their
      microenvironment.
AB  - Oncolytic viral therapy is a promising biological therapy for the treatment of
      cancer. Recent advances in genetic engineering have facilitated the construction
      of custom-built oncolytic viruses that can be exquisitely targeted to tumors by
      exploiting each cancer's unique biology and their efficacy can be further
      enhanced by "arming" them with additional therapeutic genes. Such an approach
      allows the virus to unload its "therapeutic cargo" at the tumor site, thereby
      enhancing its anti-neoplastic properties. While several clever strategies have
      been recently described using genes that can induce cellular apoptosis/suicide
      and/or facilitate tumor/virus imaging, viruses armed with genes that also affect
      the tumor microenvironment present an exciting and promising approach to therapy.
      In this review we discuss recently developed oncolytic viruses armed with genes
      encoding for angiostatic factors, inflammatory cytokines, or proteases that
      modulate the extracellular matrix to regulate tumor vascularization, anti-tumor
      immune responses and viral spread throughout the solid tumor.

PMID- 19860653
TI  - Stem cells as delivery vehicles for oncolytic adenoviral virotherapy.
AB  - Glioblastoma multiforme is the most common primary intracranial tumor in humans.
      Despite continued advances in cancer therapy, the outcome for patients diagnosed
      with this disease remains bleak. Novel treatments involving the use of
      conditionally replicating adenoviruses (CRAds) to target malignant brain tumors
      have undergone extensive research and proven to be a promising mode of
      glioblastoma therapy. CRAds are genetically manipulated to replicate within tumor
      cells, exhibiting a high degree of infectivity, cytotoxicity, and transgene
      expression. While the use of various CRAds has been deemed safe for intracranial
      injection in preclinical trials, a significant therapeutic effect has yet to be
      seen in patients. This shortcoming stems from the distribution limitations
      involved with local delivery of virolytic agents. To enhance this modality of
      treatment, stem cells have been explored as cellular vehicles in virotherapy
      applications, given that they possess an intrinsic tropism for malignant brain
      tumors. Stem cell loaded CRAd delivery offers a more specific and effective
      method of targeting disseminated tumor cells and forms the basis for this review.

PMID- 19860654
TI  - Immunotherapy of human cancers using gene modified T lymphocytes.
AB  - Adoptive T cell therapies can produce objective clinical responses in patients
      with hematologic and solid malignancies. Genetic manipulation of T lymphocytes
      has been proposed as a means of increasing the potency and range of this anti
      tumor activity. We now review how coupling expression of transgenic receptors
      with countermeasures against potent tumor immune evasion strategies is proving
      highly effective in pre-clinical models and describe how these approaches are
      being evaluated in human subjects.

PMID- 19860656
TI  - Oncolytic adenovirus: preclinical and clinical studies in patients with human
      malignant gliomas.
AB  - Oncolytic adenoviruses are emerging as a promising alternative therapy for glioma
      patients and are currently being tested in clinic. In this review, we summarize
      our experience with gene-based therapy targeting RB pathway in gliomas. Our study
      has evolved from the development of RB-expressing adenoviral vectors to the
      characterization of the oncolytic effects on gliomas of the replication competent
      adenoviruses Delta-24, Delta-24-RGD and ICOVIR. We also review the successful
      combination of the viruses with chemotherapies that are routinely used in glioma
      patients, the efficacy of Delta-24-RGD against brain tumor stem cells, the newly
      described adenovirus-induced autophagy and the potential for the systemic
      delivery of the oncolytic viruses with human mesenchymal stem cells. Finally, we
      comment on the preclinical and clinical studies of p53 expressing adenoviral
      vector and the lessons learned from the experience of Onyx-015, the first
      oncolytic adenovirus tested in clinical setting.

PMID- 19860658
TI  - Polydeoxyribonucleotide (PDRN): a safe approach to induce therapeutic
      angiogenesis in peripheral artery occlusive disease and in diabetic foot ulcers.
AB  - Peripheral arterial occlusive disease (PAOD) of lower extremities is becoming
      more prevalent worldwide. The general prognosis is particularly negative with a
      high prevalence of coronary heart disease and cerebrovascular disease. Diabetic
      foot ulcers occur in 15% of all the patients with diabetes and proceed to lower
      leg amputations. In diabetic ulcers, wound healing is impaired because of delayed
      angiogenesis. In both pathological conditions, therapeutic angiogenesis using
      angiogenic growth factors, particularly Vascular Endothelial Growth Factor VEGF,
      is expected to be a valuable treatment. The most used approaches are based on
      VEGF local delivery or gene therapy, but they failed to meet the expected primary
      goals of therapy. Adenosine receptor stimulation can induce VEGF expression in
      many types of cells and this may be achieved by stimulating the A(2A) or A(2B)
      receptor or both, following the signalling pathways activated by hypoxia.
      Polideoxyribonucleotide (PDRN) is obtained from sperm trout by an extraction
      process. The compounds hold a mixture of deoxyribonucleotides polymers with chain
      lengths ranging between 50 and 2000 bp. PDRN is able to stimulate VEGF production
      during pathological conditions of low tissue perfusion. It likely acts through
      the stimulation of A(2A) receptors. Furthermore, acute and chronic toxicity
      studies showed a good safety profile. PDRN has been shown to be effective in an
      experimental model of PAOD, hind limb ischemia, impaired wound healing and burn
      injury. Preliminary studies and ongoing clinical trials predict a significant
      therapeutic efficacy in patients. These data lead to hypothesize a role for PDRN
      in therapeutic angiogenesis.

PMID- 19860655
TI  - Gene therapy for brain cancer: combination therapies provide enhanced efficacy
      and safety.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults.
      Despite significant advances in treatment and intensive research, the prognosis
      for patients with GBM remains poor. Therapeutic challenges for GBM include its
      invasive nature, the proximity of the tumor to vital brain structures often
      preventing total resection, and the resistance of recurrent GBM to conventional
      radiotherapy and chemotherapy. Gene therapy has been proposed as a useful
      adjuvant for GBM, to be used in conjunction with current treatment. Work from our
      laboratory has shown that combination of conditional cytotoxic with
      immunotherapeutic approaches for the treatment of GBM elicits regression of large
      intracranial tumor masses and anti-tumor immunological memory in syngeneic rodent
      models of GBM. In this review we examined the currently available animal models
      for GBM, including rodent transplantable models, endogenous rodent tumor models
      and spontaneous GBM in dogs. We discuss non-invasive surrogate end points to
      assess tumor progression and therapeutic efficacy, such as behavioral tests and
      circulating biomarkers. Growing preclinical and clinical data contradict the old
      dogma that cytotoxic anti-cancer therapy would lead to an immune-suppression that
      would impair the ability of the immune system to mount an anti-tumor response.
      The implications of the findings reviewed indicate that combination of cytotoxic
      therapy with immunotherapy will lead to synergistic antitumor efficacy with
      reduced neurotoxicity and supports the clinical implementation of combined
      cytotoxic-immunotherapeutic strategies for the treatment of patients with GBM.

PMID- 19860657
TI  - AAV as a gene transfer vector for the treatment of neurological disorders: novel
      treatment thoughts for ALS.
AB  - Therapeutic delivery to the central nervous system has challenged scientists and
      clinicians due to the difficulty in delivering molecules and genes in an
      efficient manner across the blood brain barrier (BBB). This has particularly
      hampered efforts to deliver therapeutics to widely dispersed neurons that perish
      in diseases such as Amyotrophic Lateral Sclerosis (ALS), a disease affecting
      motor neurons throughout the brainstem and the entire spinal cord. Gene therapy
      has offered several potential routes to overcome the difficulties in delivering
      therapeutics to the brain and spinal cord. Adeno-associated viral vectors (AAV)
      have taken center stage for gene delivery to the central nervous system, given
      their ability to express genes in post mitotic cells for long periods with
      minimal to no toxicity. This review will focus on recent approaches to treat
      motor neuron disease, in particular ALS using AAV vectors.

PMID- 19860659
TI  - N-glycosylation engineering of biopharmaceutical expression systems.
AB  - N-glycosylation, the enzymatic coupling of oligosaccharides to specific
      asparagine residues of nascent polypeptide chains, is one of the most widespread
      post-translational modifications. Following transfer of an N-glycan precursor in
      the ER, this structure is further modified by a number of glycosidases and glyco
      syltransferases in the ER and the Golgi complex. The processing reactions
      occurring in the ER are highly conserved between lower and higher eukaryotes. In
      contrast, the reactions that take place in the Golgi complex are species- and
      cell type-specific. Due to its non-template driven nature, glycoproteins
      typically occur as a mixture of glycoforms. Since N-glycans influence circulation
      half-life, tissue distribution, and biological activity each glycoform has its
      own pharmacokinetic, pharmacodynamic and efficacy profile. Moreover, modification
      of glycoproteins with non-human oligosaccharides can result in undesired
      immunogenicity. Therefore, engineering of the N-glycosylation pathway of most
      currently used heterologous protein expression systems (bacteria, mammalian
      cells, insect cells, yeasts and plants) is actively pursued by several academic
      and industrial laboratories. These research efforts are in the first place
      directed at humanizing the N-glycosylation pathway and eliminating immunogenic
      glycotopes. Moreover, one wants to establish new structure-function relationships
      of different glycoforms, which helps to decreasing the complexity of the N-glycan
      repertoire towards one defined N-glycan structure. In this review, we discuss the
      most important recent milestones in the glycoengineering field.

PMID- 19860660
TI  - Mining the genome for susceptibility to complex neurological disorders.
AB  - Genome-wide association studies (GWAS) have become increasingly widely used to
      determine regions of the genome which may contain loci influencing the risk of
      neurological disorders. While linkage studies have identified genes that cause a
      number of Mendelian disorders, linkage analysis is less well suited for the more
      common complex disorders. This has led to the widespread use of GWAS for that
      purpose. Here we present and discuss several of the major extant GWAS in
      neurological disorders, their limitations, and implications of findings to date.

PMID- 19860661
TI  - B-type natriuretic peptide: endogenous regulator of myocardial structure,
      biomarker and therapeutic target.
AB  - B-type natriuretic peptide (BNP), initially identified in brain tissues, is now
      recognized as a key cardiac hormone. Numerous studies over the last decade have
      demonstrated that both exogenous and endogenous BNP prevent left ventricular (LV)
      hypertrophy in experimental settings, largely via activation of particulate
      guanylyl cyclase (pGC)-coupled receptors. BNP represents somewhat of a paradox,
      in that upregulation of BNP expression is widely used as a diagnostic marker for
      LV hypertrophy, diastolic dysfunction and heart failure in the clinic. We and
      others have postulated that BNP serves as an endogenous brake on the LV
      myocardium, seeking to curb the runaway train of signaling pathways that drive
      the progression from LV hypertrophy though remodeling, heart failure and death.
      This review summarizes the mechanisms of BNP's antihypertrophic actions, the role
      for cyclic GMP-mediated inhibition of pro-hypertrophic signaling, and BNP's
      impact on LV function. The improved understanding of the mechanisms of BNP
      regulation of LV hypertrophy and function that has emerged from both the
      experimental and clinical experience with this peptide provides new insight into
      the potential that BNP pharmacotherapy still offers for patients with LV
      hypertrophy.

PMID- 19860662
TI  - Prion protein misfolding.
AB  - The crucial event in the development of transmissible spongiform encephalopathies
      (TSEs) is the conformational change of a host-encoded membrane protein - the
      cellular PrP(C) - into a disease associated, fibril-forming isoform PrP(Sc). This
      conformational transition from the alpha-helix-rich cellular form into the mainly
      beta-sheet containing counterpart initiates an 'autocatalytic' reaction which
      leads to the accumulation of amyloid fibrils in the central nervous system (CNS)
      and to neurodegeneration, a hallmark of TSEs. The exact molecular mechanisms
      which lead to the conformational change are still unknown. It also remains to be
      brought to light how a polypeptide chain can adopt at least two stable
      conformations. This review focuses on structural aspects of the prion protein
      with regard to protein-protein interactions and the initiation of prion protein
      misfolding. It therefore highlights parts of the protein which might play a
      notable role in the conformational transition from PrP(C) to PrP(Sc) and
      consequently in inducing a fatal chain reaction of protein misfolding.
      Furthermore, features of different proteins, which are able to adopt insoluble
      fibrillar states under certain circumstances, are compared to PrP in an attempt
      to understand the unique characteristics of prion diseases.

PMID- 19860664
TI  - Spinal muscular atrophy: molecular mechanisms.
AB  - Spinal muscular atrophy (SMA) is a relatively common autosomal recessive
      neuromuscular disorder characterised by muscle weakness and atrophy due to
      degeneration of motor neurons of the spinal cord and cranial motor nuclei. The
      clinical phenotype incorporates a wide spectrum. No effective treatment is
      currently available and patients may experience severe physical disability which
      is often life limiting. The most common type of SMA is caused by homozygous
      disruption of the survival motor neuron 1 (SMN1) gene by deletion, conversion or
      mutation and results in insufficient levels of survival motor neuron (SMN)
      protein in motor neurons. While diagnosis is usually achieved by genetic testing,
      an illustrative clinical case is described that highlights the molecular and
      diagnostic complexities. While there is an emerging picture concerning the
      function of the SMN protein and the molecular pathophysiological mechanisms
      underpinning the disease, a number of substantial issues remain unresolved. The
      selective vulnerability of the motor neuron and the site and timing of the
      primary pathogenesis are not yet determined. Utilising the organisation of the
      SMN genomic region, recent advances have identified a number of potential
      therapeutic targets. As such, this review incorporates discussion of the clinical
      manifestations, molecular genetics, diagnosis, mechanisms of disease pathogenesis
      and development of novel treatment strategies.

PMID- 19860663
TI  - Role of beta7 integrins in intestinal lymphocyte homing and retention.
AB  - Lymphocytes involved in intestinal immune response are found in organized immune
      inductive sites of the gut-associated lymphoid tissues (GALT) such as Peyer's
      patches (PP), mesenteric lymph nodes (MLN) and diffuse effector sites of gut
      epithelium and lamina propria (LP). beta(7) integrins are responsible for
      efficient trafficking and retention of lymphocytes in these sites. Naive and
      effector lymphocytes use alpha(4)beta(7) integrin to extravasate from blood to
      gut mucosal tissues of GALT, MLN and LP via interactions with Mucosal Addressin
      Cell Adhesion Molecule-1 (MAdCAM-1). The alpha(E)beta(7) integrin facilitates
      retention of effector and memory lymphocytes in the gut epithelial layer via
      interactions with E-cadherin. Mucosal dendritic cells (DCs) regulate the
      expression of the gut homing receptors alpha(4)beta(7) integrin and the chemokine
      receptor CCR9 on activated effector and regulatory lymphocytes in a retinoic acid
      dependent manner. CD103 (alpha(E) integrin) identifies a subset of mucosal DCs in
      MLN and small intestine LP that have an enhanced ability to induce gut-tropic
      receptors on responding lymphocytes. The interactions between beta(7) integrin
      and their ligands are also implicated in the pathogenesis and progression of
      inflammatory bowel diseases (IBDs), intestinal parasitic infections and graft
      versus-host diseases. During intestinal inflammation, beta(7) integrin-dependent
      and -independent pathways contribute to lymphocytes recruitment to the intestinal
      tissues and disease pat-hogenesis. Recent works have explored the potential of
      therapeutic targeting of alpha(4) and beta(7) integrins in IBDs. Here, we review
      the current understanding of the role of beta(7) integrins in intestinal
      lymphocyte trafficking and retention in health and disease.

PMID- 19860666
TI  - Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog
      signaling activation.
AB  - Hedgehog signaling is aberrantly activated in glioma, medulloblastoma, basal cell
      carcinoma, lung cancer, esophageal cancer, gastric cancer, pancreatic cancer,
      breast cancer, and other tumors. Hedgehog signals activate GLI family members via
      Smoothened. RTK signaling potentiates GLI activity through PI3K-AKT-mediated GSK3
      inactivation or RAS-STIL1-mediated SUFU inactivation, while GPCR signaling to Gs
      represses GLI activity through adenylate cyclase-mediated PKA activation. GLI
      activators bind to GACCACCCA motif to regulate transcription of GLI1, PTCH1,
      PTCH2, HHIP1, MYCN, CCND1, CCND2, BCL2, CFLAR, FOXF1, FOXL1, PRDM1 (BLIMP1),
      JAG2, GREM1, and Follistatin. Hedgehog signals are fine-tuned based on positive
      feedback loop via GLI1 and negative feedback loop via PTCH1, PTCH2, and HHIP1.
      Excessive positive feedback or collapsed negative feedback of Hedgehog signaling
      due to epigenetic or genetic alterations leads to carcinogenesis. Hedgehog
      signals induce cellular proliferation through upregulation of N-Myc, Cyclin D/E,
      and FOXM1. Hedgehog signals directly upregulate JAG2, indirectly upregulate
      mesenchymal BMP4 via FOXF1 or FOXL1, and also upregulate WNT2B and WNT5A.
      Hedgehog signals induce stem cell markers BMI1, LGR5, CD44 and CD133 based on
      cross-talk with WNT and/or other signals. Hedgehog signals upregulate BCL2 and
      CFLAR to promote cellular survival, SNAI1 (Snail), SNAI2 (Slug), ZEB1, ZEB2
      (SIP1), TWIST2, and FOXC2 to promote epithelial-to-mesenchymal transition, and
      PTHLH (PTHrP) to promote osteolytic bone metastasis. KAAD-cyclopamine, Mu-SSKYQ
      cyclopamine, IPI-269609, SANT1, SANT2, CUR61414 and HhAntag are small-molecule
      inhibitors targeted to Smoothened, GANT58, GANT61 to GLI1 and GLI2, and Robot
      nikinin to SHH. Hedgehog signaling inhibitors should be used in combination with
      RTK inhibitors, GPCR modulators, and/or irradiation for cancer therapy.

PMID- 19860667
TI  - Effects of alpha-crystallin on lens cell function and cataract pathology.
AB  - The development of cataracts is a debilitating eye condition which is common in
      elderly patients and afflicts millions worldwide. Cataracts result from the
      deposition of aggregated proteins in the eye which causes clouding of the lens,
      light scattering, and obstruction of vision. Non-syndromic, hereditary human
      cataract development is linked to point mutations in the CRYAA and CRYAB genes
      which encode alphaA and alphaB-crystallin. The alpha-crystallins are small heat
      shock proteins which play central roles in maintaining lens transparency and
      refractive properties. The discovery in 1992 that these proteins possess
      chaperone-like activity has led most researchers to focus on the ability of alpha
      crystallins to prevent protein aggregation in vitro. While the ability of alpha
      crystallins to efficiently trap aggregation-prone denatured proteins in vitro is
      thought to delay the development of age-related cataracts in vivo, alpha
      crystallins have additional functions which may also contribute to cataract
      pathology. In addition to chaperone activity, alpha-crystallins are known to
      protect cells from stress-induced apoptosis, regulate cell growth, and enhance
      genomic stability. They also physically and functionally interact with both the
      cell membrane and cytoskeleton. Functional changes in alpha-crystallin have been
      shown to modify membrane and cell-cell interactions and lead to lens cell
      pathology in vivo. This article focuses on the multiple diverse roles of alphaA
      crystallin in the maintenance of lens function and cataract development in vivo.

PMID- 19860665
TI  - HSP27: mechanisms of cellular protection against neuronal injury.
AB  - The heat shock protein (HSP) family has long been associated with a generalized
      cellular stress response, particularly in terms of recognizing and chaperoning
      misfolded proteins. While HSPs in general appear to be protective, HSP27 has
      recently emerged as a particularly potent neuroprotectant in a number of diverse
      neurological disorders, ranging from ALS to stroke. Although its robust
      protective effect on a number of insults has been recognized, the mechanisms and
      regulation of HSP27's protective actions are still undergoing intense
      investigation. On the basis of recent studies, HSP27 appears to have a dynamic
      and diverse range of function in cellular survival. This review provides a forum
      to compare and contrast recent literature exploring the protective mechanism and
      regulation of HSP27, focusing on neurological disorders in particular, as they
      represent a range from protein aggregate-associated diseases to acute stress.

PMID- 19860668
TI  - Dendritic cells: a new player in osteoimmunology.
AB  - Recent studies have suggested that the dys-regulated progressive immune responses
      in some inflammatory conditions can lead to significantly increased osteoclasts
      (OC) frequency and activity associated with active bone destruction; termed
      inflammation-induced bone loss. Among the inflammatory infiltrates,
      monocytes/macrophages (Mo/MQ), T and B cells, have been well studied and
      documented as central players in osteoimmunological interactions
      (osteoimmunology: is an interdisciplinary field linking the immune and skeletal
      systems). We and others investigated the role(s) of dendritic cells (DC) during
      inflammation-induced osteoclastogenesis and bone loss. In addition to their
      innate effector functions, DC are potent professional antigen-presenting cells
      (APC) involved in triggering and orchestrating adaptive immunity, thereby
      implicated as potential osteo-immune players. Herein, bone remodeling and DC's
      biology including their development and functions are reviewed along with the
      contribution of DC at the crossroad of the osteo-immune interface during the
      process of inflammation-induced osteoclastogenesis. Furthermore, we provide a
      summary of recent progress, and discuss a proposed alternative mechanism
      underlying inflammation-induced bone loss. Understanding the cellular and
      molecular mechanisms regulating DC's roles in inflammation-induced
      osteoclastogenesis and bone loss might benefit future treatment approaches,
      especially if targeting DC can be translated into therapeutic strategies to
      ameliorate both tissue inflammation and bone destruction during disease
      progression associated with inflammatory bone diseases.

PMID- 19860669
TI  - Cosignaling molecules around LIGHT-HVEM-BTLA: from immune activation to
      therapeutic targeting.
AB  - The regulation of the immune system at the cell surface is primarily controlled
      by two families of cosigaling molecules: the immunoglobulin (Ig) superfamily, or
      "CD28 and B7 family", and the tumor necrosis factor receptor (TNFR) family. Here,
      we summarized the principal structural and functional characteristics of both
      families. In this respect, the interaction between HVEM, a TNF receptor, and
      BTLA, an Ig family member, has provided a new perspective and an additional level
      of complexity in the crosstalk between these two regulatory systems. This review
      will present a summary of the recent advances in the immunobiology of the LIGHT
      HVEM-LTbetaR-BTLA network. The LIGHT-HVEM-BTLA system has emerged as a major
      regulator of immune responses and lymphocyte activation, whereas LIGHT-LTbetaR
      participates in lymphoid tissue development and cell death. Moreover, recent
      studies have provided encouraging new insights into the roles of the LIGHT-HVEM
      LTbetaR-BTLA axis as a potential target for controlling anti-tumor responses.

PMID- 19860670
TI  - MHC and MHC-like molecules in the design of vaccines.

PMID- 19860671
TI  - Prediction of MHC-peptide binding: a systematic and comprehensive overview.
AB  - T cell immune responses are driven by the recognition of peptide antigens (T cell
      epitopes) that are bound to major histocompatibility complex (MHC) molecules. T
      cell epitope immunogenicity is thus contingent on several events, including
      appropriate and effective processing of the peptide from its protein source,
      stable peptide binding to the MHC molecule, and recognition of the MHC-bound
      peptide by the T cell receptor. Of these three hallmarks, MHC-peptide binding is
      the most selective event that determines T cell epitopes. Therefore, prediction
      of MHC-peptide binding constitutes the principal basis for anticipating potential
      T cell epitopes. The tremendous relevance of epitope identification in vaccine
      design and in the monitoring of T cell responses has spurred the development of
      many computational methods for predicting MHC-peptide binding that improve the
      efficiency and economics of T cell epitope identification. In this report, we
      will systematically examine the available methods for predicting MHC-peptide
      binding and discuss their most relevant advantages and drawbacks.

PMID- 19860672
TI  - Characterization of MHC ligands for peptide based tumor vaccination.
AB  - Short peptides derived from cellular proteins may escape complete destruction
      during protein catabolism and finally serve as a showcase in the immune system.
      Exposed at the cell surface to scrutiny by T cells, MHC:peptide complexes mediate
      a highly specific and immediate information transfer from diseased cells to the
      cellular immune system. Numerous clinical vaccination trials have been carried
      out employing MHC-presented peptides for T-cell activation with encouraging
      results but so far without a final breakthrough. In this review, we briefly
      highlight the molecular basis of MHC-peptide interactions governed by specificity
      pockets and anchor residues, as summarized in allele-specific peptide motifs.
      State-of-the-art technology is comprehensively presented and gives an overview of
      modern mass spectrometric strategies used for qualitative and quantitative
      analysis of MHC ligands. We describe the details of the HLA-B*3801 peptide motif
      by comparing features of natural MHC ligands, resulting in a scoring matrix that
      enables epitope prediction from any viral or tumor antigen. The pronounced
      individuality in peptide presentation by MHC molecules, as reflected in the
      highly specific peptide motifs of different MHC allotypes or the tissue-specific
      MHC ligandomes, represents a current area of interest within this field. Finally,
      the identification of post-translational modifications--most important
      phosphorylations--and the promises this holds will be discussed in this chapter.

PMID- 19860673
TI  - Models of antigen receptor activation in the design of vaccines.
AB  - Vaccination techniques have developed rapidly over the last several decades from
      the immunization with live attenuated pathogens to the use of peptide and DNA
      subunit vaccines, from the use of classical adjuvants to cell-directed delivery.
      Vaccination techiques are also under investigation for the treatment of tumors
      and autoimmune diseases. However, profound knowledge of activation mechanisms of
      the immune cells on a molecular level is prerequisite for a better understanding
      of the immune response, and for the development of effective immunomodulatory
      tools. In this review we discuss the models of BCR and TCR activation, and using
      the example of some vacciantion technologies, we show, how the understanding of
      these models could help in the design of a new generation of vaccines.

PMID- 19860675
TI  - Use of MHC II structural features in the design of vaccines for organ-specific
      autoimmune diseases.
AB  - The Major Histocompatibility Complex Class II locus is the primary genetic
      linkage to autoimmune diseases. Susceptibility to each such disease is linked to
      different alleles, with a few alleles showing also dominant protection. The
      design of vaccines for autoimmune diseases is a long sought-after goal. As
      knowledge about the pathogenesis of these diseases has increased, the tools for
      such an approach have of necessity been refined. We review below the structural
      essence of MHC II-linked autoimmune diseases which centers on the binding of
      antigenic peptides to the disease-linked MHC II proteins, and the consequent
      activation of cognate TCRs from pathogenic CD4+ T cells. The state of affairs in
      two organ-specific autoimmune diseases, type 1 diabetes, celiac disease are
      covered, including attempts to treat these via antigen-specific MHC II-guided
      measures. We offer a couple of testable suggestions as to how this approach could
      be improved.

PMID- 19860676
TI  - Non-canonical peptides bound to MHC.
AB  - Central to the initiation of a T cell dependent immune response is the
      recognition of major histocompatibility complex (MHC) class I or class II
      molecules (in humans termed HLA and in mice termed H-2) bound to antigenic
      peptide. T cell receptors (TCR) have programmed specificity for particular
      peptide/MHC complexes, which ensures focused immune responses are generated
      against the antigen source. To design effective peptide based vaccines a
      comprehensive understanding of the specific interactions between MHC molecules
      and peptide, and of TCR recognition of MHC/peptide is valuable. We place
      particular emphasis on non-canonical bound peptides and their use in
      immunotherapy studies.

PMID- 19860677
TI  - "Self-nonself" peptides in the design of vaccines.
AB  - What makes a peptide an epitope? This is a central question in immunology. The
      clear identification of precise molecular characteristics of epitopes would help
      define the basic mechanisms of self/non-self distinction and lead to a greater
      understanding of phenomena such as tolerance, autoimmunity, allergy, and tumor
      escape of immune surveillance. Importantly, clarifying the properties an epitope
      is paramount to the development of diagnostic and therapeutic vaccines. This
      review analyzes recent reports on experimentally identified B cell epitopes
      associated with multiple infectious disease pathologies, cancer, autoimmunity,
      hypertension, obesity, and allergy. It illustrates data that further support the
      notion that only a low level of sequence similarity to the host proteome is
      needed to modulate the B cell epitope-specific peptidome. Amino acid sequences
      that are unique to the antigen and are not shared with the host proteome are
      specifically targeted by the humoral immune response. Therefore, low-similarity
      peptides may be significant to the rational development of peptide-based clinical
      treatments in cancer, autoimmunity, infection, and allergy. Biologically, the low
      similarity hypothesis further supports sequence uniqueness as the molecular
      signature of "nonselfness" in the currently ongoing self/non-self debate.

PMID- 19860674
TI  - HLA-DR: molecular insights and vaccine design.
AB  - Vaccines are one of the most cost effective methods to control infectious
      diseases and at the same time one of the most complex products of the
      pharmaceutical industry. In contrast to other drugs, vaccines are used mainly in
      healthy individuals, often in children. For this reason, very high standards are
      set for their production. Subunit vaccines, especially peptide vaccines, can
      provide a safe and cost-effective alternative to vaccines produced from
      attenuated or inactivated pathogen preparations. Biochemical and structural
      studies of class II MHC-peptide complexes are beginning to provide a conceptual
      foundation for the rational design of subunit and peptide vaccines. In this
      review, we show how analysis of peptide-class II MHC complexes together with
      developing understanding of antigen processing pathways has opened the door to
      understanding the major rules that govern selection of T cell epitopes. We review
      progress towards computational prediction of such epitopes, and efforts to
      evaluate algorithms that incorporate various structural and/or biochemical
      aspects of the MHC-peptide interaction. Finally, using malaria as a model, we
      describe the development of a minimal subunit vaccine for the human malaria
      parasite Plasmodium falciparum.

PMID- 19860678
TI  - The TCR/CD3 complex: opening the gate to successful vaccination.
AB  - The success of vaccination is directly or indirectly based on the specificity of
      antigen recognition by T lymphocytes, their efficient activation and expansion,
      and the generation of vaccine-specific effectors and memory cells. These traits
      are largely dependent on the correct assembly and expression of sufficient number
      of functional TCR/CD3 complexes in the cell surface. In this review, some of the
      genetic and epigenetic factors that determine the correct assembly and structure
      of the TCR/CD3 complex are summarized. Those physiologic or pathologic factors
      leading to natural variations, or pathologic alterations of the standard that
      might lead to poor response to vaccination and that could give some possibilities
      to pharmacological intervention are emphasized.

PMID- 19860679
TI  - NK cell receptors and their interactions with MHC.
AB  - MHC-specific Natural Killer inhibitory receptors display a conserved and
      fundamental function in the regulation of NK-mediated cytolysis. Their importance
      is substantiated by the fact that during speciation different molecular receptor
      structures have evolved to maintain inhibitory regulation of NK cells. The
      information gained during these last twenty years begins to be fruitfully used in
      the therapy of leukemias, but a lot has to be still done. In particular, we need
      to understand the role of activating KIR and their ligand(s), since their role in
      the course of different viral diseases is still intriguing.

PMID- 19860680
TI  - Presentation of lipid antigens by CD1 glycoproteins.
AB  - CD1 molecules are a family of non-polymorphic, class I antigen-presenting
      glycoproteins, which bind and present amphiphilic lipid antigens for recognition
      to T cells. Two groups of CD1 molecules are involved in presentation of self and
      foreign lipid antigens: group 1 (CD1a, CD1b and CD1c) and group 2 (CD1d). Crystal
      structures of CD1a, CD1b and CD1d in complex with different ligands have revealed
      the key principles of lipid presentation and defined unique binding groove
      architectures for the individual CD1 isoforms, which enable binding and
      presentation of an enormous variety of lipids. Structural and biochemical
      insights into presentation of glycolipids by CD1d have led to the discovery of
      novel lipid antigens and to a broader understanding of the underlying structural
      and mechanistic principles of NKT cell stimulation. Some of these glycolipids
      show enhanced and more specific stimulatory properties and crystal structures
      have suggested further design strategies for elicitation of immuno-stimulatory
      compounds that may enable selective control of the secretion of regulatory T
      helper cytokines.

PMID- 19860682
TI  - HPLC and MS analysis for the identification and characterisation of peptides
      presented in the context of the non-classical human leukocytes antigen (HLA)
      class I molecule HLA-E.
AB  - In addition to a variety of other techniques used in T-cell epitope
      identification, mass spectrometery coupled to liquid chromatography have now
      become an important and sensitive tool in separation, detection, and sequence
      analysis of highly complex natural major histocompatibility complex (MHC) ligand
      mixtures. In this article, we present current strategies for the identification
      of MHC eluted peptides using high-performance liquid chromatography coupled to
      tandem mass spectrometry (HPLC-MS/MS) with a particular recall to those presented
      in the context of the non classical human leukocytes antigen (HLA) class I
      molecule HLA-E. In addition we also discuss the advantages and disadvantages of
      the methods available in the literature to concentrate and fractionate the
      peptides prior to analysis by mass spectrometry. An application of our method for
      isolation and characterization of peptides presented in the context of HLA-E is
      finally reported.

PMID- 19860681
TI  - HLA-G molecule.
AB  - Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule, which
      was first discovered in 1987 by Geraghty and colleagues. While classical HLA
      class I molecules are expressed on all nucleated cells, the expression of the HLA
      G molecule is highly tissue-restricted, such as to placental trophoblast cells.
      HLA-G binds inhibitory receptors such as leukocyte immunoglobulin-like receptors
      B1 (LILRB1/ILT2/CD85j) and LILRB2 (ILT4/CD85d), which are widely expressed on
      immune cells, to suppress a broad range of immune responses. Thus, the expression
      of HLA-G in placenta protects the fetus from the maternal immune system. On the
      other hand, emerging studies have shown the relevance of the HLA-G molecule in
      pathologic conditions, such as transplantation rejection, autoimmunity, and
      cancer. HLA-G has other unique characteristics, in contrast with classical HLA
      molecules, including the existence of various forms of HLA-G: several splice
      variants, subunit-deficient conformations, homodimers, and their combinations
      have been found. In this review, we highlight the molecular basis for the
      tolerogenic ability of the HLA-G molecule, especially by LILR recognition of
      various forms of HLA-G. We also discuss the potential clinical applications of
      HLA-G molecules.

PMID- 19860683
TI  - HLA-E and HLA-E-bound peptides: recognition by subsets of NK and T cells.
AB  - In humans, major histocompatibility complex (MHC) class I molecules comprise the
      classical (class Ia) human leukocyte antigens (HLA)-A, -B, and -C, and the non
      classical (class Ib) HLA-E, -F, -G and -H (HFE) molecules. The best-characterized
      MHC class Ib molecule is HLA-E. HLA-E was first described as a non-polymorphic
      ligand of the CD94/NKG2 receptors expressed mainly by natural killer (NK) cells
      and its role was thus confined to the regulation of NK cell function. Therefore,
      interaction of HLA-E with the CD94/NKG2 receptors can result in either inhibition
      or activation of NK cells, depending on the peptide presented and on the NKG2
      receptor CD94 is associated with. Thus, CD94/NKG2A functions as an inhibitory
      receptor, whereas CD94/NKG2C functions as an activating receptor. However, recent
      evidences obtained by our group and others indicated that HLA-E represents a
      novel restriction element for ab T-cell receptor (TCR)-mediated recognition.
      Although HLA-E displays a selective preference for nonameric peptides derived
      from the leader sequences of various HLA class I alleles, several reports showed
      that it can also present "non-canonical" peptides derived from both stress
      related and pathogen-associated proteins. Because HLA-E displays binding
      specificity for innate CD94/NKG2 receptors but also has the features of an
      antigen-presenting molecule--including the ability to be recognized by ab T cells
      -it does appear that this MHC class Ib molecule plays an important role in both
      natural and acquired immune responses.

PMID- 19860684
TI  - Simultaneous optimization of potency, selectivity and physicochemical properties
      for cannabinoid CB(2) ligands.
AB  - Non-selective cannabinoid ligands display a wide range of physiological effects
      including analgesic, anti-inflammatory, anti-convulsive and immuno-suppressive
      activities. A separation between therapeutic effects and undesirable CNS side
      effects may be accomplished by increasing the selectivity for the CB(2) receptor
      over the CB(1) receptor. There is considerable interest in developing new
      cannabimimetic compounds possessing preferentially high affinity for the CB(2)
      receptor as potential novel therapeutics for the treatment of inflammation and
      chronic pain. This review will summarize the literature on selective cannabinoid
      CB(2) receptor agonists from 2007 to the present, with special emphasis on SAR
      and medicinal chemistry strategies to improve physicochemical properties,
      metabolic stability and oral bioavailabilty of these inherently lipophilic
      ligands. Incorporating physicochemical property filters early in hit
      identification, concurrent screening of liver microsomal stability and addressing
      metabolic hot-spots through structural modifications or bio-isosteric
      replacements during lead optimization led to a number of structurally diverse
      CB(2) agonists with good oral bioavailability and in vivo efficacy in rodent
      models of pain.

PMID- 19860685
TI  - Pathophysiological insights into atrial fibrillation following cardiac surgery:
      implications for current pharmaceutical design.
AB  - Atrial fibrillation (AF) following cardiac surgery is a common complication,
      which increases incidence of other complications, hospital and healthcare costs.
      The reported rate of the occurrence of postoperative AF varies with different
      studies, depending on population profile, type of surgery, arrhythmia definition
      and detection methods, design of study. Nonetheless, the precise mechanisms of AF
      related to cardiac surgery are poorly understood. A diverse variety of reasons
      have been proposed for the pathogenesis of this common cardiac arrhythmia. The
      aim of this review article is to provide an overview of pathophysiological
      processes that lead to the development of AF post-cardiac surgery. These
      processes are closely inter-related but the most important ones that have bearing
      on drug design include the RAAS, ion channels, connexins, fibrosis and
      extracellular matrix turnover, inflammation and oxidative stress. The autonomic
      nervous system and structural remodeling all influence all these
      pathophysiological processes, which should not be viewed in isolation.
      Understanding such processes would have major implications for the approach to
      current pharmaceutical design, to improve our approach to drug management
      strategies.

PMID- 19860686
TI  - Developing novel therapeutic approaches to frailty.
AB  - Frailty is now defined as a clinical entity and potentially responsive to
      medications. This article reviews the drugs available and those under
      development. While, at present, exercise is the primary therapy, it is expected
      over the next decade that numerous drugs will be available to treat components of
      the frailty syndrome.

PMID- 19860687
TI  - Role of chemokines and their receptors in cancer.
AB  - Metastases are the cause of 90% of human cancer deaths. The current treatment of
      cancer with chemo,- and/or radiotherapy is based on cell death by DNA damage
      neglecting the fact that cancer cell invasion into surrounding tissues and
      metastasizing are fundamental features of neoplasms and the major reason for
      treatment failure. Metastasis is the result of several sequential steps and
      represents a highly organized, non-random, and organ-selective process. A number
      of in vitro and in vivo models show that tumor cells use chemokine-mediated
      mechanisms during this metastasizing process, comparable to those observed in the
      regulation of leukocyte trafficking. Furthermore, chemokines modulate tumor
      behavior such as the regulation of tumor-associated angiogenesis, activation of
      host tumor-specific immunological responses, and direct stimulation of tumor cell
      proliferation in an autocrine fashion. These findings may lead to new drugs that
      target chemokines or their receptors and will likely be of great additional value
      for treatment of cancer patients.

PMID- 19860688
TI  - Vascular damage in impaired glucose tolerance: an unappreciated phenomenon?
AB  - Impaired glucose tolerance (IGT) is an independent risk predictor for
      cardiovascular morbidity and mortality, as well as for total mortality,
      independent of the subsequent development of overt diabetes mellitus. Increased
      rates of major adverse cardiac event and shorter survival in subjects with IGT
      who are post acute myocardial infarction have also been observed. The aim of this
      review article is to provide an overview of the pathophysiological basis of IGT
      and the actual mechanism(s) of vascular damage, accounting for its impact in
      cardiovascular disease (CVD). We focus on endothelial damage, aberrant
      angiogenesis and apoptosis-the three important pathophysiological mechanisms
      responsible for most long term complications in frank diabetes. However, on this
      occasion we evaluate these mechanisms in the milieu of IGT (post prandial
      hyperglycaemia or post challenge hyperglycaemia) rather than frank diabetes per
      se. A better understanding of the actual mechanisms of vascular damage in IGT may
      not only enhance our understanding about the disease process but may also
      facilitate implementation of appropriate therapeutic measures.

PMID- 19860689
TI  - Mast cells: target and source of neuropeptides.
AB  - Mast cells, originating from bone marrow pluripotential cells are generally
      populated near to strategic locations of mammalian body. They store a wide
      variety of biologically active molecules in their granules and also can de novo
      synthesize an additional spectrum of mediators, depending on their
      microenvironment, phenotype and status. Mast cells have numerous receptors that
      can trigger a wide spectrum of cellular responses, some of them which can be
      preprogrammed against specific pathogens. Mast cells secrete mediators, go under
      total degranulation, or degranulate only some of the specific granules with
      required content according to the environmental conditions, pathogens or
      signaling molecules binding to their receptors. Mast cells are functionally multi
      faceted cells. A single cell can behave such as an immune cell, an endocrine cell
      and even as a sensorial neuron. In this context, mast cells can significantly
      influence inflammation, tissue remodeling, host defense and homeostasis.
      Specifically the mast cells proximal to nerve fibers, contain, secrete and
      respond to, several neuropeptides, suggesting many potential functions for mast
      cells in health and disease. Mast cells are target cells for neuropeptides and,
      they have distinct profiles of responsiveness to these molecules. This extends
      the flexibility of neurogenic signaling pathways via reciprocity. Those
      neuropeptides have direct and indirect effects on mast cells such as inducing or
      suppression of degranulation, triggering, modulation or amplification of mediator
      content and release. The exploration of interactions of mast cells and neurons is
      a promising field of study which may bring treatments to several diseases. Since
      mast cells seem to form the major link between neurons and inflammation via
      neuropeptides, mast cell and mast cell mediator connection may lead to a better
      understanding of the autocrine, paracrine, and neuro-immune-endocrine systems in
      physiology and physiopathology. Therefore, mast cell manipulator drug designs,
      capable of granular content modulation, with effects on, selective mediator
      release, activity and, ablation of mast cells, would be very beneficial for the
      treatment of various diseases that mast cells may be involved in.

PMID- 19860690
TI  - Drug combinations for dyslipidemia and obesity treatment in metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a cluster of risk factors, each one individually
      associated with increased cardiovascular disease risk. Treatment of all
      components of MetS is expected to result in reduced risk. Treatment of MetS
      mainly includes lifestyle changes. In addition, drug therapy may be considered,
      especially combinations of different drugs, in order to tackle all the features
      of MetS. We review the therapeutic strategies currently used for obesity and
      dyslipidemia treatment in patients with MetS, with a focus on drug combinations.

PMID- 19860691
TI  - Phosphodiesterase-5 inhibitors and their use in the treatment of urological
      conditions.

PMID- 19860692
TI  - PDE5 inhibitors: in vitro and in vivo pharmacological profile.
AB  - PDE5 inhibitors have been clearly established as first-line therapy for the
      treatment of erectile dysfunction (ED). Three PDE5 inhibitors--sildenafil
      (Viagra), vardenafil (Levitra) and tadalafil (Cialis)--are currently approved by
      the FDA and the EMEA for use in ED, whereas sildenafil is also marketed under a
      different proprietary name (Revatio) for the treatment of pulmonary arterial
      hypertension (PAH). A forth PDE5 inhibitor, udenafil (Zydena), is currently
      marketed. In the present review the molecular basis and the mechanism of action
      of PDE5 inhibitors is discussed. In addition experimental and clinical data
      concerning their effects on different tissues, organs and systems is
      systematically reviewed and their possible beneficial action in numerous
      disorders is presented.

PMID- 19860693
TI  - Phosphodiesterase type 5 inhibitors: unmet needs.
AB  - Erectile dysfunction (ED) has been revolutionized during the last two decades, as
      several treatment options are available today. Phosphodiesterase type 5 (PDE5)
      inhibitors (sildenafil, tadalafil, vardenafil) are currently the first choice
      treatment option for ED by most physicians and patients due to their high
      efficacy rates and favourable safety profiles. Despite the fact that more than 50
      million ED patients have been treated successfully worldwide with PDE5i several
      issues remain to be addressed. Patients with severe neurologic damage, diabetes
      mellitus, or severe vascular disease may be resistant to PDE5i. Inappropriate
      instructions, lack of follow-up and lack of patient-centered care models have
      been identified as main reasons for "nonresponse", leading to drop-out rates of
      even > 50%. Preservation of corporal smooth muscle with chronic administration of
      PDE5i has been reported and there is a substantial body of evidence for
      beneficial effects of these drugs on endothelium and cardiovascular function.
      Finally, improvement of lower urinary symptoms after PDE5i administration has
      been reported and a possible role on treatment of premature ejaculation has been
      proposed. Many new PDE5i are candidates to enter the market in the forthcoming
      years. However, pharmacokinetic differences should be obvious to consider a truly
      better option for patients. Patients must be aware of all treatment options since
      no ideal treatment exists and physicians must offer personalized medicine to
      their patients in the future. The development and adaptation of a patient
      centered care model in sexual medicine will increase efficacy and safety of
      current and future treatments.

PMID- 19860694
TI  - Phosphodiesterase type 5 inhibitors for the management of erectile dysfunction:
      preference and adherence to treatment.
AB  - Erectile dysfunction (ED) is a common medical condition that has a negative
      impact on men and their partners. The field has revolutionised over the last two
      decades and more treatment options are available now for the treatment of ED than
      ever before. Among available treatment options, the most commonly prescribed
      therapies are oral phosphodiesterase type 5 (PDE5) inhibitors. The first drug in
      this class, sildenafil citrate, generally provides patients and their partners
      with efficacious, safe, and discreet treatment that rapidly has become the first
      line treatment option. Its successful introduction into clinical practice was
      soon followed by the launch of two other PDE5 inhibitors: tadalafil and
      vardenafil. The existence of these drugs has resulted in an increase in their
      marketing. However, the abundance of choices made the question "which PDE-5
      inhibitor?" relevant for clinicians, patients and their partners. It is widely
      accepted that there are no significant differences in their safety and efficacy,
      a fact that has led to the initiation of studies aiming to evaluate them
      regarding patient preference. Nevertheless, the results are rather conflicting.
      Also a significant percentage of men initiating treatment switch between
      inhibitors or discontinue therapy. This article examines the peer-reviewed
      published data addressing patient's preference and adherence to ED treatment with
      PDE5 inhibitors. It also examines strategies to improve compliance and
      satisfaction with treatment.

PMID- 19860695
TI  - Prophylaxis of erectile function after radical prostatectomy with
      phosphodiesterase type 5 inhibitors.
AB  - Erectile dysfunction (ED) is one of the most challenging complications associated
      with radical prostatectomy (RP) for clinically localized prostate cancer.
      Currently, a broad spectrum of therapeutic options are available to improve
      sexual health after surgical treatment. Several basic science reports highlighted
      a potential role for phosphodiesterase type 5 inhibitors in the prevention of
      endothelial damage related to ischemia reperfusion and/or denervation following
      surgery. Recent studies have shown that pharmacological prophylaxis soon after RP
      can significantly improve the rate at which erectile function is recovered after
      surgery. Use of on-demand treatments for ED in patients who have undergone RP has
      been shown to be highly effective. In this context, pharmacological prophylaxis
      potentially may have a significantly expanded role in future strategies aimed at
      preserving postoperative erectile function. We analyzed the factors affecting
      erectile function after RP and evaluated the evidence suggesting the role of
      pharmacological prophylaxis and treatment of ED after surgery.

PMID- 19860696
TI  - PDE5 inhibitors in the treatment of LUTS.
AB  - Both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have a
      negative impact on patients' quality of life. The co-prescription of two active
      agents for these conditions will improve each condition and the addition of one
      drug to the other may potentiate the primary response of the first treatment and
      thereby improve the QoL of patients. Several epidemiological studies have
      indicated that the association between LUTS and ED is more than a co-incidence of
      age, with a possible cause and effect relationship. LUTS is more common in men
      with ED and there is a strong relationship between the severity of LUTS and the
      degree of erectile difficulty. Four pathophysiologies have been suggested to
      explain the relationship between LUTS and ED. There is a complex interaction
      between these mechanisms and there may be additional processes involved. These
      are: (1) alteration in nitric oxide levels; (2) autonomic hyperactivity; (3)
      changes in the Rho-kinase/endothelin pathway; and (4) pelvic vasculature
      atherosclerosis. Studies of all three easily available PDE-5 inhibitors have
      shown improvements in both LUTS and ED in men with significant problems in both
      areas without any substantial increase in side effect profile. Studies have also
      shown that the greatest improvements occurred with the combination of an alpha
      blocker and PDE-5 inhibitor when compared with either drug alone. Whilst
      significant improvements were seen in LUTS symptom scores, there was no
      significant improvement in flow rates with PDE-5 inhibitors when compared with
      placebo. High quality basic science studies of PDE-5 inhibitors on bladder muscle
      and alpha blocker agents on penile cavernosal tissue have provided several
      explanations for their modes of action. Even so, the mechanism of action of PDE-5
      inhibitors in LUTS remains far from certain. More well-designed, placebo
      controlled studies are needed to confirm the impact of these drugs, alone or in
      combination, on both ED and LUTS. However combination therapy appears appropriate
      for patients with both LUTS and ED. At present though, we should not routinely
      offer a combination of PDE-5 inhibitors and alpha blocker for the treatment of
      LUTS alone.

PMID- 19860697
TI  - Is there a role for PDE5 inhibitors in the management of male infertility due to
      defects in testicular or epididymal function?
AB  - This review study refers to the possibility to employ PDE5 inhibitors as an
      adjunct tool for the therapeutic management of male infertility. The literature
      tends to suggest that PDE5 inhibitors enhance the Leydig cell secretory function
      and play a role in the regulation of the contractility of the tunica albuginea
      and the epididymis. In addition, the literature suggests that PDE5 inhibitors
      increase the prostatic secretory function that results in an improvement in sperm
      motility in several cases. Some studies additionally demonstrate a role of PDE5
      inhibitors in the regulation of sperm capacitation process. Additional placebo
      controlled, randomized, blind studies are necessary to unequivocally suggest a
      therapeutic role of PDE5 inhibitors in the alleviation of semen disorders and
      male infertility.

PMID- 19860698
TI  - PDE5 inhibitors in non-urological conditions.
AB  - Phosphodiesterase type-5 (PDE5) inhibitors are widely used as first-line therapy
      for erectile dysfunction (ED). Their efficacy and safety combined with an
      increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated
      mechanisms, have triggered a number of attempts to determine their effects and
      potential benefits in non-urological conditions. In recent years, extensive and
      diverse preclinical and clinical evidence has been made available. PDE5
      inhibition has shown collateral benefits for a multitude of risk factors or
      diseases associated with, or accompanying ED. To date, PDE5 inhibition has been
      shown to be effective for the treatment of idiopathic pulmonary arterial
      hypertension and both sildenafil and tadalafil are approved for this indication.
      However, PDE5 inhibitors appear to have the potential of further expanding their
      indications. Importantly, accumulating data show that the therapeutic potential
      extends to the cardiovascular, gastrointestinal, cutaneous and nervous system and
      that these agents may be beneficial in a multitude of conditions such as
      Raynaud's phenomenon, heart failure, essential hypertension and stroke. PDE5
      inhibitors are a conceptually attractive therapeutic class of agents with
      pleiotropic effects. The present review discusses recent findings regarding the
      effects of PDE5 inhibitors on non-urological conditions and highlights current
      and future clinical applications beyond ED.

PMID- 19860699
TI  - Phosphodiesterase-5 inhibitors: future perspectives.
AB  - PDE-5 inhibitors were originally studied in cardiovascular indications but were
      later developed and approved for on-demand treatment of erectile dysfunction
      (ED). A few years ago sildenafil was approved for the treatment of pulmonary
      hypertension, thus renewing interest in cardiovascular applications, and
      tadalafil became available in once-daily formulations for erectile dysfunction
      management. Given the wide distribution of phosphodiesterase-5 throughout the
      body and its involvement in multiple functions, what can one expect in the
      future? To answer this we reviewed studies involving PDE-5 inhibitors that were
      published within the past three years and searched the US National Institutes of
      Health clinical trial registry for ongoing ones. PDE-5 inhibitors are being
      actively investigated in many disease states, with interest focusing mainly on
      urology and cardiovascular medicine. In urology erectile dysfunction is the
      primary target, followed by BPH-related lower urinary tract symptoms. As far as
      cardiovascular medicine is concerned, treatment of heart failure is the
      indication where PDE-5 inhibitors seem to be closer to clinical application but
      preclinical data also support a role in cardiac preconditioning.

PMID- 19860700
TI  - Recent advances of fluorescent technologies for drug discovery and development.
AB  - Recent progresses in the development of fluorescent technologies become a
      reliable device for drug discovery research. The fluorescence tools offer
      attractive options for an opportunity to visualize the effects of drug candidates
      in the cells. The fluorescent tools, such as fluorescent protein, are regularly
      used in a range of drug discovery processes. A better understanding and use of
      fluorescent technologies facilitate drug discovery research faster and can open
      up new applications. Therefore, we have provided information about some new
      generation fluorescent reagents (GFP and fluorophores). This review illustrates
      how fluorescent technologies and fluorescent tools are contributing to the drug
      discovery process mainly high-throughput screening (HTS), disease mechanism based
      target discovery, disease-genes-based target discovery, 'target classes' based
      target candidate discovery, physiology-based drug discovery, genomics-based drug
      discovery, target validation and their future perspectives.

PMID- 19860701
TI  - Role of calcitonin gene-related Peptide in gastric mucosal defence and healing.
AB  - Calcitonin gene-related peptide (CGRP) is a polypeptide produced by alternative
      processing of calcitonin gene transcripts and is endowed with important systemic
      physiological effects. The recent characterization of its receptor and the
      discovery of stable antagonists has addressed them in the indication migraine.
      Beside this, several studies have been focused on role of CGRP at gastric level.
      CGRP is considered a marker of afferent fibers in the upper gastrointestinal
      tract being almost completely depleted following treatment with the selective
      neurotoxin capsaicin that targets these fibers via transient receptor potential
      vanilloid of type-1. The exogenous administration of the peptide was able to
      afford protection against experimental ulcers induced by an increase in gastric
      secretion. The use of CGRP knockout mice has let to characterize the endogenous
      role of CGRP showing that the local release of this neuropeptide protects from
      ethanol injury and favours ulcer healing. Decreased levels of gastric CGRP-like
      immunoreactivity (li) were observed during acetic acid-, cysteamine-,
      concentrated ethanol- or water immersion stress-ulcers. Restoration of CGRP-li
      was found in animals bearing ulcers in healing status and delayed healing in mice
      knockout to CGRP. CGRP was able to release somatostatin from gastric D cells but
      its main effects on the stomach homeostasis rely on local vasodilator action
      during increased acid-back diffusion.

PMID- 19860702
TI  - Fibroblast growth factor-2 antagonist and antiangiogenic activity of long
      pentraxin 3-derived synthetic peptides.
AB  - Angiogenesis and inflammation are closely integrated processes. Fibroblast growth
      factor-2 (FGF2) is a prototypic angiogenesis inducer belonging to the family of
      the heparin-binding FGF growth factors. FGF2 exerts its pro-angiogenic activity
      by interacting with various endothelial cell surface receptors, including
      tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. A tight
      cross-talk exists between FGF2 and the inflammatory response in the modulation of
      blood vessel growth. Pentraxins act as soluble pattern recognition receptors with
      a wide range of functions in various pathophysiological conditions. The long
      pentraxin PTX3 shares the C-terminal pentraxin-domain with short-pentraxins and
      possesses a unique N-terminal domain. These structural features indicate that
      PTX3 may have distinct biological/ligand recognition properties when compared to
      short-pentraxins. Co-expression of PTX3 and FGF2 has been observed in different
      inflammation/angiogenesis-dependent diseases. PTX3 binds FGF2 with high affinity
      and specificity. The interaction prevents the binding of FGF2 to its cognate
      tyrosine kinase receptors, leading to inhibition of the angiogenic activity of
      the growth factor. This suggests that PTX3 may exert a modulatory function by
      limiting the angiogenic activity of FGF2. An integrated approach that utilized
      PTX3 fragments, monoclonal antibodies, and surface plasmon resonance analysis has
      identified the FGF2-binding domain in the unique N-terminal extension of PTX3. On
      this basis, PTX3-derived synthetic peptides have been designed endowed with a
      significant antiangiogenic activity in vitro and in vivo. They may provide the
      basis for the development of novel antiangiogenic FGF2 antagonists.

PMID- 19860703
TI  - Tony Fink (1943-2008): scientist, teacher and artist.

PMID- 19860704
TI  - Editorial.

PMID- 19860705
TI  - Sugar sulfamates for seizure control: discovery and development of topiramate, a
      structurally unique antiepileptic drug.
AB  - TOPAMAX((R)) (topiramate) 1, is a broad-spectrum anticonvulsant that has been
      marketed worldwide for the treatment of epilepsy and migraine. We discovered this
      blockbuster drug serendipitously in a project that originally sought a new
      antidiabetic agent. Topiramate has useful neurological effects that derive from
      multiple CNS mechanisms of action, but it is basically a "neurostabilizer" by
      virtue of attenuating the excitability of brain neuronal pathways. During its
      extensive clinical use, topiramate was also found to possess antimetabolic
      dysfunction activity, which could be applicable in the treatment of diabetes and
      obesity. This article discusses research results and events surrounding the
      discovery and development of topiramate.

PMID- 19860706
TI  - RNAi and related technologies: applications in medicinal chemistry and drug
      discovery.

PMID- 19860707
TI  - RNA interference-based gene expression strategies aimed at sustained therapeutic
      inhibition of HIV.
AB  - The naturally-occurring RNA interference (RNAi) pathway represents a powerful
      tool for the sequence-specific post-transcriptional silencing of gene expression.
      By exploiting the endogenous mammalian RNAi pathway, several expression-based
      strategies have been developed to inhibit human immunodeficiency virus (HIV) gene
      expression and replication. This approach potentially has utility as a protective
      'therapeutic vaccine' of virus-susceptible lymphocytes. In this review we discuss
      new developments aimed at improving efficacy and delivery of novel RNAi-based
      gene expression antiviral strategies. Particular attention is given to advances
      in combinatorial gene expression systems that prevent the emergence of RNAi
      resistant virus by simultaneously targeting multiple HIV targets. Potential
      usefulness of silencing host factors that are required for viral replication is
      also discussed. These approaches form the basis for a number of promising ongoing
      and future clinical trials aimed at providing an effective, safe and prolonged
      single-intervention therapy for HIV/AIDS.

PMID- 19860708
TI  - Transcriptional regulation by promoter targeted RNAs.
AB  - Small RNA molecules, including small interfering RNA (siRNA) and micro RNA
      (miRNA), have rapidly emerged as important regulators of gene expression. Recent
      articles have demonstrated RNA mediated complex induced transcriptional gene
      silencing (TGS) occurring in the nucleus. Originally the small RNA mediated TGS
      pathway has been reported in yeast and plants, currently a number of articles
      strongly suggest that this newly established gene silencing mechanism is present
      in mammals. RNA mediated TGS has been reported for various human promoters
      including inhibition of tumor susceptibility genes, X-chromosome inactivation and
      suppression of human chemokine receptor. Small RNAs can inhibit human viral
      infection through the TGS pathway. Prolonged HIV-1 transcriptional gene silencing
      by an RNA duplex targeting a sequence located within the HIV-1 promoter has been
      reported initially using a susceptible adherent cell line model and recently
      prolonged suppression of productive HIV-1 infection in a T-cell line model has
      been demonstrated by a retrovirally delivered short-hairpin RNA (shRNA) targeting
      the same region. RNA mediated gene silencing in HIV-1 infection can induce
      heterochromatin (closed) structure in the promoter regions, which is consistent
      to those changes seen in studies of various RNA directed TGS in various human
      promoter regions. More recent observations suggest transcriptional activation can
      be induced through RNA duplexes targeting the human promoter of E-cadherin, p21
      and the progesterone receptor. Although the precise mechanisms of how RNA
      mediated transcriptional gene silencing or activation functions has yet to be
      elucidated, this review describes linkage of small RNA mediated gene regulation
      and induction of epigenetic regulation in the promoter region in mammals.

PMID- 19860709
TI  - Peptide mediated siRNA delivery.
AB  - Applying RNA interference to silence a specific gene has opened a new and
      promising avenue of gene therapy. But a key bottleneck is the poor stability and
      inability of naked siRNA to translocate through cell membranes. Among several
      delivery systems, cationic peptides capable of penetrating cell membranes have
      drawn attention due to their structural and functional versatility, potential
      biocompatibility and ability to target cells. In this review, different classes
      of peptides employed in siRNA delivery are reviewed. In particular, a new class
      of siRNA delivery peptides with high transfection efficiency and low cytotoxicity
      is introduced.

PMID- 19860710
TI  - Enhanced gene delivery and/or efficacy by functional peptide and protein.
AB  - RNA interference (RNAi) is an attractive phenomenon for practical use that
      specifically inhibits gene expression and is carried out by small double-stranded
      RNAs (dsRNAs) including small interfering RNA (siRNA) or short hairpin RNA
      (shRNA). In addition, RNAi is of great interest for clinical use to cure
      refractory diseases related to the expression of a specific gene. To achieve gene
      silencing in the body, a sufficient amount of dsRNA must be delivered and
      internalized into target cells. However, dsRNAs have a large molecular weight and
      net negative charge, which limits their membrane-permeating ability. Moreover,
      dsRNAs are rapidly degraded by endonucleses in the body. Therefore, for the
      efficient delivery of dsRNAs, many approaches based on drug delivery systems have
      been carried out. In this review, we focus on recent reports about the
      application of functional peptides and proteins designed for the efficient
      delivery of dsRNAs.

PMID- 19860711
TI  - Phosphorothioate-stimulated uptake of siRNA by mammalian cells: a novel route for
      delivery.
AB  - The efficient delivery of biologically functional short interfering RNA (siRNA)
      in vivo remains a widely unresolved technical problem in therapeutic drug
      development. The repertoire of concepts for the cellular uptake of
      oligonucleotide-based tools and drugs has been extended by the mechanistically
      novel finding that phosphorothioate (PS)-modified single-stranded
      oligodeoxyribonucleotides (ON) promote the intracellular accumulation of naked
      extra-cellular siRNA in a variety of cell types. This mode of delivery gives rise
      to substantial intracellular amounts of siRNA, up to 10(4) siRNA molecules per
      cell. Conversely, the moderate biological effectiveness strongly indicates that
      intracellular release of siRNA from sub-cellular compartments where it seems to
      be trapped is a necessary step towards efficient target suppression. Here, we
      summarize key characteristics of the PS-stimulated cellular uptake of siRNA and
      describe concepts for the increase of intracellular delivery of biologically
      functional siRNA.

PMID- 19860712
TI  - Systemic delivery and quantification of unformulated interfering RNAs in vivo.
AB  - Synthetic small interfering RNAs (siRNAs) open promising new therapeutic
      perspectives in acute and chronic pathologies. A number of experiments in mice
      demonstrated the ability of naked siRNAs injected under a normal pressure to
      trigger gene silencing in vivo, translating into a measurable phenotype. We focus
      in this review on the information that we can gain from these experiments, and
      discuss how the specificity of the gene silencing in vivo can be controlled.
      Because the activity of most drugs increases with the dosing, we are prone to
      consider that increasing the concentration of siRNAs within cells enhances the
      efficiency and the duration of the silencing. However, because RNAi is a
      saturable process, and because increasing the siRNA concentration into cells can
      induce undesirable side effects, this must be demonstrated. We compare in this
      review the methods used to quantify and study the biodistribution of siRNAs in
      living animals, and discuss how these methods can help in designing for each
      model and each siRNA the most adequate protocol to silence a cognate target gene
      in vivo.

PMID- 19860713
TI  - Lentiviral delivery of RNAi effectors against HIV-1.
AB  - RNA interference (RNAi) holds great promise as gene therapy approach against
      viral pathogens, including HIV-1. A specific anti-HIV-1 response can be induced
      via transfection of synthetic small interfering RNAs (siRNAs) or via
      intracellular transgene expression of short hairpin RNAs (shRNAs) or microRNAs
      (miRNAs). Both targeting of the viral mRNAs or the mRNAs for cellular co-factors
      that are required for viral replication have been shown successful in suppressing
      HIV-1 replication. However, like conventional mono-therapies, the use of a single
      anti-HIV-1 RNAi inducer results in the emergence of RNAi-escape mutants. To
      prevent viral escape, a combinatorial RNAi approach should be used in which
      multiple RNAi effectors against HIV-1 are simultaneously expressed. Although
      induced RNAi is able to trigger a robust and specific knockdown of virus
      replication, it is becoming apparent that RNAi therapeutics encounter
      difficulties concerning off-target effects, cellular toxicity and specific
      delivery to the right cells. This review covers the recent progress in
      combinatorial RNAi-based approaches against HIV-1 using lentiviral vectors as a
      delivery system. The potential for a clinical gene therapy application will be
      discussed.

PMID- 19860714
TI  - The therapeutic potential of cell-internalizing aptamers.
AB  - Aptamers that are evolved by the SELEX procedure (Systematic Evolution of Ligands
      by Exponential enrichment) can specifically recognize and tightly bind their
      cognate targets by means of well-defined secondary and three-dimensional
      structures. In comparison to antibodies, nucleic acid-based aptamers offer some
      exciting advantages, including the potential for chemical synthesis, convenient
      modification, chemical versatility, stability and lack of immunogenicity. During
      the past 20 years, aptamers have been developed for various applications such as
      diagnostics, drug development, target validation and therapeutics. Aptamers
      targeting cell surface proteins are being explored as promising delivery vehicles
      to target a distinct disease or tissue in a cell-type-specific manner. In this
      review, we summarize the recent developments in creatively using cell
      internalizing aptamers as drug delivery escorts to deliver, enhance and modulate
      the activity of other therapeutic agents, including chemical drugs, toxins, small
      interfering RNAs and nanoparticle-encapsulated drugs. Specifically, several
      attractive aptamer-mediated cell-type specific siRNA delivery systems are
      highlighted, and their promise in clinical development is also discussed.

PMID- 19860715
TI  - Structural genomics.

PMID- 19860717
TI  - Carboxylesterases: a world with still words to say.

PMID- 19860716
TI  - Structural genomics and drug discovery for infectious diseases.
AB  - The application of structural genomics methods and approaches to proteins from
      organisms causing infectious diseases is making available the three dimensional
      structures of many proteins that are potential drug targets and laying the
      groundwork for structure aided drug discovery efforts. There are a number of
      structural genomics projects with a focus on pathogens that have been initiated
      worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was
      recently established to apply state-of-the-art high throughput structural biology
      technologies to the characterization of proteins from the National Institute for
      Allergy and Infectious Diseases (NIAID) category A-C pathogens and organisms
      causing emerging, or re-emerging infectious diseases. The target selection
      process emphasizes potential biomedical benefits. Selected proteins include known
      drug targets and their homologs, essential enzymes, virulence factors and vaccine
      candidates. The Center also provides a structure determination service for the
      infectious disease scientific community. The ultimate goal is to generate a
      library of structures that are available to the scientific community and can
      serve as a starting point for further research and structure aided drug discovery
      for infectious diseases. To achieve this goal, the CSGID will determine protein
      crystal structures of 400 proteins and protein-ligand complexes using proven,
      rapid, highly integrated, and cost-effective methods for such determination,
      primarily by X-ray crystallography. High throughput crystallographic structure
      determination is greatly aided by frequent, convenient access to high-performance
      beamlines at third-generation synchrotron X-ray sources.

PMID- 19860718
TI  - Characterisation of oxidized recombinant human galectin-1.
AB  - Oxidized human galectin-1 plays a role in the immune response to injured axons.
      Over-expression of galectin-1 by cancer, in combination with cancer associated
      oxidative stress suggests oxidized human galectin-1 may also play a role(s) in
      tumourigenesis. Here we generate milligram quantities of oxidized human galectin
      1 and undertake biophysical characterization. The protein adopts a number of
      different states. Two separable oxidized forms are identified that exist as
      largely mono-disperse solutions at higher milligram/ml concentrations. The
      presence of disulphide bonds is confirmed for these two protein forms, as is
      their change in overall shape and loss of lectin activity. Our studies lead to
      production of a particular mono-disperse oxidized human galectin-1 species that
      is anticipated most optimal for investigations requiring milligram/ml
      concentrations such as X-ray crystallography.

PMID- 19860722
TI  - beta-Amyloid fibrillation and/or hyperhomocysteinemia modify striatal patterns of
      hyaluronic acid and dermatan sulfate: Possible role in the pathogenesis of
      Alzheimer's disease.
AB  - A key event in Alzheimer's disease (AD) pathogenesis is the formation of
      insoluble peptides beta-amyloid aggregates and this process is favoured by a
      condition of hyperhomocysteinemia. To date, there is growing evidence that
      implicates glycosaminoglycans (GAGs) in the pathophysiology of amyloidosis but no
      data are available on the characterization of brain GAGs involved in the
      enhancing beta-amyloid fibrillogenesis in relationship to their structure and
      physico-chemical properties. Furthermore, few studies have been performed on the
      relationship between hyperhomocysteinemia and extracellular matrix (ECM)
      modifications. The aim of this study was to evaluate the amount and chemical
      structure of GAGs in rat striatal areas where beta-amyioid fibrillogenesis was
      induced, and in conditions of hyperhomocysteinemia. The intrastriatal injection
      of beta-amyloid produced a significant decrease (-40.8%) in the hyaluronic acid
      (HA) percentage and an increase (+14.5%) in the dermatan sulfate (DS) with a
      total charge density increasing of 14.9%. A significant decrease (-19.5%) in the
      HA percentage and an increase (+6.9%) in the DS % was also observed in striata
      obtained from the hyperhomocysteinemic animals. The total charge density
      increased by 6.8%. Quite the same trend was observed in rats after intrastriatal
      injection of beta-amyloid and in a condition of hyperhomocysteinemia. The
      observed increase of DS concentration and the correspondent decrease of the
      nonsulfated polymer HA after in vivo treatment with beta-amyloid and in a
      condition of hyperhocysteinemia support the hypothesis that an increase in local
      production of sulfated GAGs may reduce beta-amyloid neurotoxicity. However, the
      consequent modification of the ECM network might impair the extracellular
      diffusion pathways of different signal molecules and participate in the
      progression of AD.

PMID- 19860723
TI  - Origins, controversies and recent developments of the MCI construct.
AB  - The MCI construct aims to investigate the grey area existing between normal aging
      and dementia, in order to identify it in the preclinical stage patients at risk
      of developing dementia. The construct of the MCI has been proposed by taking the
      neuropathological staging of the Alzheimer's disease (AD) as reference and
      providing an explicit set of identifying criteria, but it has raised two main
      problems: (a) the variability of estimates concerning the actual rate of
      conversion from MCI to dementia, and (b) the number of subjects who return to
      normality. These problems stem in part from the operational difficulties met by
      the MCI identifying criteria concerned with: the memory tests used, the cut-off
      adopted to identify patients with an 'objective' memory disorder, the assessment
      of subjective memory disorders, and the integrity of daily living activities.
      After a short discussion of these operational difficulties, I will pass to
      shortly survey the laboratory data providing additional predictive value for the
      conversion of MCI to dementia (ApoE4, CSF biomarkers, Neuroimaging data, and
      Vascular risk factors) and some recent attempts to identify pre-MCI patients,
      with a purely subjective cognitive impairment. I will conclude my review by
      asking if we have a single MCI or a family of MCI constructs, each of whom could
      play a preferential role in specific clinical contexts.

PMID- 19860724
TI  - A new hypothesis of pathogenesis based on the divorce between mitochondria and
      their host cells: possible relevance for Alzheimer's disease.
AB  - On the basis of not only the endosymbiotic theory of eukaryotic cell organization
      and evolution but also of observations of transcellular communication via
      Tunneling NanoTubes (TNTs), the hypothesis is put forward that when mitochondria,
      which were once independently living prokaryote-like organisms, are subjected to
      detrimental genetic, toxic, or environmental conditions, including age-related
      endogenous factors, they can regress towards their original independent state. At
      that point, they can become potentially pathogenic intruders within their
      eukaryotic host cell. Because of the protoplasmic disequilibrium caused by an
      altered, or mutated, mitochondral population, certain host cells with a minimal
      capacity for self-renewal, such as dopaminergic neurons, risk a loss of function
      and degenerate. It is also proposed that altered mitochondria, as well as their
      mutated mtDNA, can migrate, via TNTs, into adjacent cells. In this way,
      neurodegenerative states are propagated between cells (glia and/or neurons) of
      the Central Nervous System (CNS) and that this leads to conditions such as
      Alzheimer's and Parkinson's disease. This proposal finds indirect support from
      observations on rotenone-poisoned glioblastoma cells which have been co-cultured
      with non-poisoned cells. Immunocytochemical techniques revealed that
      mitochondria, moving along the TNTs, migrated from the poisoned cells towards the
      healthy cells. It has also been demonstrated by means of immunocytochemistry
      that, in glioblastoma cell cultures, Amyloid Precursor Protein (APP) is present
      in TNTs, hence it may migrate from one cell to neighbouring cells. This datum may
      be of high relevance for a better understanding of Alzheimer's Disease (AD) since
      molecular, cellular, and animal model studies have revealed that the formation of
      amyloid beta (Abeta) and other derivatives of the APP are key pathogenic factors
      in AD, causing mitochondrial dysfunction, free radical generation, oxidative
      damage, and inflammation. Furthermore, the present data demonstrate the presence
      of alpha-synuclein (alpha-syn) within TNTs, hence a similar pathogenic mechanism
      to the one surmised for AD, but centred on alpha-syn rather than on Abeta, may
      play a role in Parkinson's Disease (PD). As a matter of fact, alpha-syn can enter
      mitochondria and interact with complex I causing respiratory deficiency and
      increased oxygen free radical production. In agreement with this view, it has
      been demonstrated that, in comparison with normal subjects, PD patients show a
      significant accumulation of alpha-syn at Substantia Nigra and Striatal level,
      predominantly associated with the inner mitochondrial membrane,. These
      observations suggest that potentially neuropathogenic proteins, such as Abeta and
      alpha-syn, can not only diffuse via the extracellular space but also move from
      cell to cell also via TNTs where they can cause mitochondrial damage and cell
      degeneration. A mathematical model (see Appendix) is proposed to simulate the
      pathogenic consequences of the migration of altered mitochondria and/or of their
      mtDNA via TNTs. The results of the present simulation is compatible with the
      proposal that mutated mitochondrial agents behave as though they were infectious
      particles migrating through a continuum of interconnected cells.

PMID- 19860726
TI  - The I.F.A.S.T. model allows the prediction of conversion to Alzheimer disease in
      patients with mild cognitive impairment with high degree of accuracy.
AB  - This paper presents the results obtained with the innovative use of special types
      of artificial neural networks (ANNs) assembled in a novel methodology named IFAST
      (implicit function as squashing time) capable of compressing the temporal
      sequence of electroencephalographic (EEG) data into spatial invariants. The aim
      of this study is to test the potential of this parallel and nonlinear EEG
      analysis technique in providing an automatic classification of mild cognitive
      impairment (MCI) subjects who will convert to Alzheimer's disease (AD) with a
      high degree of accuracy. Eyes-closed resting EEG data (10-20 electrode montage)
      were recorded in 143 amnesic MCI subjects. Based on 1-year follow up, the
      subjects were retrospectively classified to MCI converted to AD and MCI stable.
      The EEG tracks were successively filtered according to four different frequency
      ranges, in order to evaluate the hypotheses that a specific range, corresponding
      to specific brain wave type, could provide a better classification (0.12 Hz, 12.2
      - 29.8 Hz; 30.2 - 40 Hz, and finally Notch Filter 48 - 50 Hz). The spatial
      content of the EEG voltage was extracted by IFAST step-wise procedure using ANNs.
      The data input for the classification operated by ANNs were not the EEG data, but
      the connections weights of a nonlinear auto-associative ANN trained to reproduce
      the recorded EEG tracks. These weights represented a good model of the peculiar
      spatial features of the EEG patterns at scalp surface. The classification based
      on these parameters was binary and performed by a supervised ANN. The best
      results distinguishing between MCI stable and MCI/AD reached to 85.98%.(012 Hz
      band). And confirmed the working hypothesis that a correct automatic
      classification can be obtained extracting spatial information content of the
      resting EEG voltage by ANNs and represent the basis for research aimed at
      integrating spatial and temporal information content of the EEG. These results
      suggest that this low-cost procedure can reliably distinguish eyes-closed resting
      EEG data in individual MCI subjects who will have different prognosis at 1-year
      follow up, and is promising for a large-scale periodic screening of large
      populations at amnesic MCI subjects at risk of AD.

PMID- 19860727
TI  - Neurogenesis and Alzheimer's disease: Biology and pathophysiology in mice and
      men.
AB  - The hippocampus is critical for learning and memory and heavily affected in
      dementia. The presence of stem cells in this structure has led to an increased
      interest in the phenomenon of adult neurogenesis and its role in hippocampal
      functioning. Not surprising, investigators of Alzheimer's disease have also
      evaluated adult neurogenesis due to its responsiveness to hippocampal damage.
      Although causal relationships have not been established, many factors known to
      impact neurogenesis in the hippocampus, are implicated in the pathogenesis of AD.
      Also, adult neurogenesis has been proposed to reflect a "neurogenic reserve" that
      may determine vulnerability to hippocampal dysfunction and neurodegeneration.
      Since neurogenesis is modifiable, stimulation of this process, or the potential
      use of stem cells, recruited endogenously or implanted by transplantation, has
      been speculated as a possible treatment of neurodegenerative disorders. As the
      structural and molecular mechanisms governing adult neurogenesis are important
      for evaluating therapeutic strategies, we will here review collective literature
      findings and speculate about the future of this field with a focus on findings
      from Alzheimer's mouse models. Continued research in this area and use of these
      models is critical for evaluating if neurogenesis based therapeutic strategies
      will indeed have the potential to aid those with degenerative conditions.

PMID- 19860729
TI  - Assays for identification of Hsp90 inhibitors and biochemical methods for
      discriminating their mechanism of action.
AB  - The Hsp90-dependence of many oncogenic proteins has precipitated a great deal of
      interest in Hsp90 as a drug target, as evidence mounts that Hsp90 inhibitors may
      be effective chemotherapeutic agents for the treatment of cancer. In addition,
      Hsp90-inhibitors have shown promise for the treatment of neurodegenerative
      diseases characterized by the accumulation of toxic denatured protein aggregates.
      The development of assays for the identification of novel Hsp90 inhibitors began
      in earnest when it became apparent that the Hsp90 inhibitors available at the
      time had less than ideal pharmacological properties. This review summarizes what
      is known about Hsp90's structure and function, its ATPase cycle, its interactions
      with co-chaperones and clients, and the effect of Hsp90-inhibitors on these
      processes. It further summarizes various high throughput assays (and secondary
      confirmatory assays) developed to identify new Hsp90 inhibitors from chemical
      libraries based on the inhibitors ability to: inhibit Hsp90's ATPase activity;
      compete for ligand binding to Hsp90 and its N-terminal ATP-binding domain;
      inhibit Hsp90-dependent refolding of denatured luciferase; and deplete culture
      cells of Hsp90-dependnet client protein or induce Hsp70 expression. In addition,
      in vitro assays are described that help determine the site of inhibitor binding
      to Hsp90 (N- or C-terminal domain) and there mechanism of action based on effects
      of inhibitors on Hsp90/ co-chaperone and client interactions, and Hsp90
      conformation characterized by proteolytic fingerprinting.

PMID- 19860730
TI  - Update on Hsp90 inhibitors in clinical trial.
AB  - Twenty-five years ago the first small molecule inhibitors of Hsp90 were
      identified. In the intervening years there has been dramatic progress in basic
      scientific understanding of the Hsp90 chaperone machinery and in the role of
      Hsp90 in malignancy. The first-in-class Hsp90 inhibitor 17-AAG entered into Phase
      I clinical trials in 1999. There are now 13 Hsp90 inhibitors in clinical trial,
      representing multiple drug classes, and hundreds of patients have been treated in
      adult oncology and pediatric oncology trials. This review will provide an
      overview of the clinical trial results thus far. In addition, pivotal issues in
      further development of Hsp90 inhibitors as anticancer drugs will be discussed.

PMID- 19860733
TI  - Hsp90 inhibition with resorcyclic acid lactones (RALs).
AB  - Heat shock protein 90 (Hsp90) is an ATP-dependent chaperone which is involved in
      the post-translational maturation and stabilization of over one hundred proteins
      ("its clients"). In the absence of Hsp90's chaperoning, its clients are misfolded
      and degraded via ubiquitin-proteasome pathway. It has become the focus of intense
      drug discovery efforts as its activity has been implicated in diverse pathologies
      ranging from oncology to neurodegenerative and infectious diseases. The most
      promising inhibitors reported to date inhibit the ATPase activity by binding to
      the N-terminal ATP pocket. Radicicol, a member of the resorcylic acid lactones
      (RALs), represents an important pharmacophore to this end. Efforts towards the
      development of this pharmacophore and its SAR are reviewed herein.

PMID- 19860732
TI  - Purine-scaffold Hsp90 inhibitors.
AB  - Hsp90 is a molecular chaperone with important roles in regulating the function of
      several proteins with potential pathogenic activity. Because many of these
      proteins are involved in cancer and neurodegenerative promoting pathways, Hsp90
      has emerged as an attractive therapeutic target in these diseases. Molecules that
      bind to the N-terminal nucleotide pocket of Hsp90 inhibit its activity, and
      consequently, disrupt client protein function. A number of these inhibitors from
      several chemical classes are now known, and some are already in clinical trials.
      This review focuses on the purine class of Hsp90 inhibitors, their discovery
      through rational design, and on efforts aimed towards their optimization and
      development into clinically viable drugs for the treatment of cancer. Their
      potential towards neurodegenerative diseases will also be touched upon.

PMID- 19860731
TI  - Alternate strategies of Hsp90 modulation for the treatment of cancer and other
      diseases.
AB  - The 90 kDa heat shock protein (Hsp90) has become a validated target for the
      development of anti-cancer agents. Several Hsp90 inhibitors are currently under
      clinical trial investigation for the treatment of cancer. All of these agents
      inhibit Hsp90's protein folding activity by binding to the N-terminal ATP binding
      site of the Hsp90 molecular chaperone. Administration of these investigational
      drugs elicits induction of the heat shock response, or the overexpression of
      several Hsps, which exhibit antiapoptotic and pro-survival effects that may
      complicate the application of these inhibitors. To circumvent this issue,
      alternate mechanisms for Hsp90 inhibition that do not elicit the heat shock
      response have been identified and pursued. After providing background on the
      structure, function, and mechanism of the Hsp90 protein folding machinery, this
      review describes several mechanisms of Hsp90 modulation via small molecules that
      do not induce the heat shock response.

PMID- 19860734
TI  - Ansamycin inhibitors of Hsp90: nature's prototype for anti-chaperone therapy.
AB  - The ansamycin class of natural products is well known for its anti-tumor effects
      and has been extensively studied by cancer researchers for nearly four decades.
      The first description of geldanamycin in the scientific literature appeared in
      1970 and nearly thirty years later the semi-synthetic derivative 17-AAG, or
      tanespimycin, entered Phase 1 clinical trials. In the subsequent years, three
      additional geldanamycin derivatives have entered clinical evaluation. Kosan
      Biosciences developed 17-DMAG or alvespimycin hydrochloride for clinical
      evaluation as both an intravenous and oral product. Infinity Pharmaceuticals is
      developing IPI-504 or retaspimycin hydrochloride as an intravenous product, which
      is in several Phase 2 clinical trials; IPI-504 is the hydroquinone hydrochloride
      salt of 17-AAG. More recently, Infinity Pharmaceuticals initiated a Phase 1
      clinical trial with an oral formulation of 17-AG (IPI-493), the major metabolite
      of 17-AAG and IPI-504. Since a vast amount of scientific literature exists
      regarding the ansamycin field and Hsp90 inhibition, this review will survey key
      milestones in the development of the natural product class as anti-cancer drugs
      including discovery of the compounds and their anti-tumor effects, identification
      of Hsp90 as their biological target, the structure-activity relationships that
      have been identified in this interesting class of compounds, and development of
      clinical candidates for the treatment of cancer patients. A brief overview of
      important pre-clinical development data from each clinical lead is also provided.

PMID- 19860735
TI  - Structural and computational biology of the molecular chaperone Hsp90: from
      understanding molecular mechanisms to computer-based inhibitor design.
AB  - The molecular chaperone Hsp90 (90 kDa heat-shock protein) mediates many
      fundamental cellular pathways involved in cell proliferation, cell survival, and
      cellular stress response. Hsp90 is responsible for the correct conformational
      development, stability and function in crowded cell environments. Structural and
      computational biology studies have recently provided important insights into
      underlying molecular mechanisms of Hsp90 function. These developments have
      revealed a critical role of Hsp90 structure, conformational dynamics and
      interdomain communication in promoting the binding and release of ligands and its
      interaction with client proteins. By disabling multiple signal transduction
      pathways, Hsp90 inhibition provides a powerful therapeutic strategy in cancer
      research, which is selective for specific cancer mechanisms, yet broadly
      applicable to disparate tumors with different genetic signatures. Herein, we
      review the recent developments in structural and computational studies of Hsp90
      function and binding, with the emphasis on progress towards computational
      structure-based discovery and design of Hsp90 inhibitors. We also review the
      emerging insights from computational and structure-based approaches to develop
      anticancer therapies that can target novel allosteric binding sites and Hsp90
      interactions with co-chaperones and client proteins. Structural and computational
      biology studies can provide a foundation for the design of Hsp90 modulators
      capable of regulating functional protein motions linked to biological activities.
      We highlight current challenges in translating molecular mechanisms of the
      molecular chaperone into therapeutic strategies and outline future directions for
      the computer-based design of Hsp90 inhibitors.

PMID- 19860736
TI  - Strategies for stalling malignancy: targeting cancer's addiction to Hsp90.
AB  - Hsp90 is involved in the maturation and activation of client proteins. Often
      these are key proteins involved in signal transduction and regulatory pathways
      that in a mutated and/or deregulated form sustain an oncogenic cellular state.
      Consequently, the malignancy is maintained with the aid of Hsp90 upon which the
      mutated proteins have become particularly dependent for their activity. The
      requirement for the Hsp90 chaperone machine to drive the malignancy makes Hsp90 a
      prime anticancer target, an 'axle in a wheel' that when disrupted has been shown
      to be effective in killing cancerous cells. This review aims to identify
      potential drug targets, based on the current structural knowledge of the Hsp90
      chaperone machine, that could be targeted with the aim of disrupting its
      functioning and promoting an anti-cancer activity.

PMID- 19860738
TI  - Development of cationic colloidal silica-coated magnetic nanospheres for highly
      selective and rapid enrichment of plasma membrane fractions for proteomics
      analysis.
AB  - PM (plasma membrane) proteins play critical roles in many biological processes
      and are often used as molecular targets for drug discovery. In PM proteome
      research, fast and highly selective methods for PM preparation are highly
      desirable for efficient PM protein identification. In the present study, an
      improved PM isolation technique involving coating intact cells with synthesized
      cationic silica-coated magnetic nanospheres was developed and applied to the
      proteomic analysis of the PM from human erythroleukaemia K562 cells. Western
      blotting characterization and protein identification of the prepared PM indicated
      that the PM enrichment method using the prepared magnetic nanospheres is a fast
      and inexpensive strategy with high specificity. Our results demonstrate the
      potential of these cationic silica-coated magnetic nanospheres for high
      throughput identification of PM proteins from cells.

PMID- 19860739
TI  - In vitro small intestinal epithelial cell growth on a nanocomposite
      polycaprolactone scaffold.
AB  - Tissue engineering of the small intestine remains experimental despite worldwide
      attempts to develop a functional substitute for short bowel syndrome. Most
      published studies have reported predominant use of PLLA (poly-L-lactide acid)/PGA
      (polyglycolic acid) copolymer as the scaffold material, and studies have been
      limited by in vivo experiments. This lack of progress has inspired a fresh
      perspective and provoked further investigation and development in this field of
      tissue engineering. In the present paper, we exploit a relatively new
      nanocomposite of POSS (polyhedral oligomeric silsesquioxane) and PCL
      [poly(caprolactone-urea)urethane] as a material to develop porous scaffolds using
      a solvent casting/particulate leaching technique to fabricate porous scaffolds in
      different pore sizes and porosities. Scaffolds were characterized for pore
      morphology and porosity using scanning electron microscopy and micro-computed
      tomography. Rat intestinal epithelial cells were then seeded on to the polymer
      scaffolds for an in vitro study of cell compatibility and proliferation, which
      was assessed by Alamar Blue and lactate dehydrogenase assays performed for 21
      days post-seeding. The results obtained demonstrate that POSS-PCL nanocomposite
      was produced as a macroporous scaffold with porosity over the range of 40-80% and
      pore size over the range of 150-250 microm. This scaffold was shown to support
      epithelial cell proliferation and growth. In conclusion, as a further step in
      investigating small intestinal tissue engineering, the nanocomposite employed in
      this study may prove to be a useful alternative to poly(lactic-co-glycolic acid)
      in the future.

PMID- 19860740
TI  - Characterization of the haem oxygenase protein family in Arabidopsis  thaliana
      reveals a diversity of functions.
AB  - HOs (haem oxygenases) catalyse the oxidative cleavage of haem to BV (biliverdin),
      iron and carbon monoxide. In plants, the product of the reaction is BV IXalpha,
      the precursor of the PHY (phytochrome) chromophore and is thus essential for
      proper photomorphogenesis. Arabidopsis thaliana contains one major biochemically
      characterized HO (HY1) and three additional putative HOs (HO2, HO3 and HO4). All
      four proteins are encoded in the nucleus but contain chloroplast translocation
      sequences at their N-termini. The transit peptides of all four proteins are
      sufficient for chloroplast translocalization as shown by GFP (green fluorescent
      protein) reporter gene fusions. Overall, all four proteins can be divided into
      two subfamilies: HO1 and HO2. Here we show that all members of the HO1 subfamily
      (HY1, HO3 and HO4) are active monomeric HOs and can convert haem to BV IXalpha
      using spinach Fd (ferredoxin) as an electron donor. Addition of a second electron
      donor, such as ascorbate, led to a 10-fold increase in the haem conversion rate.
      Furthermore, haem turnover is also promoted by light when spinach thylakoids are
      present. All HO1 family members displayed similar kinetic parameters indicating
      they all have a possible involvement in PHY chromophore biosynthesis. HO2 did not
      yield sufficient amounts of soluble protein and therefore required the
      construction of a synthetic gene adapted to the codon usage of Escherichia coli.
      HO2 is unable to bind or degrade haem and therefore it is not a haem oxygenase.
      However, HO2 shows strong binding of proto IX (protoporphyrin IX), a precursor
      for both haem and chlorophyll biosynthesis. A possible function of HO2 in the
      regulation of tetrapyrrole metabolism is discussed.

PMID- 19860741
TI  - Crystal structure of the human transcription elongation factor DSIF hSpt4 subunit
      in complex with the hSpt5 dimerization interface.
AB  - The eukaryotic transcription elongation factor DSIF [DRB (5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole) sensitivity-inducing factor] is composed of two
      subunits, hSpt4 and hSpt5, which are homologous to the yeast factors Spt4 and
      Spt5. DSIF is involved in regulating the processivity of RNA polymerase II and
      plays an essential role in transcriptional activation of eukaryotes. At several
      eukaryotic promoters, DSIF, together with NELF (negative elongation factor),
      leads to promoter-proximal pausing of RNA polymerase II. In the present paper we
      describe the crystal structure of hSpt4 in complex with the dimerization region
      of hSpt5 (amino acids 176-273) at a resolution of 1.55 A (1 A=0.1 nm). The
      heterodimer shows high structural similarity to its homologue from Saccharomyces
      cerevisiae. Furthermore, hSpt5-NGN is structurally similar to the NTD (N-terminal
      domain) of the bacterial transcription factor NusG. A homologue for hSpt4 has not
      yet been found in bacteria. However, the archaeal transcription factor RpoE"
      appears to be distantly related. Although a comparison of the NusG-NTD of
      Escherichia coli with hSpt5 revealed a similarity of the three-dimensional
      structures, interaction of E. coli NusG-NTD with hSpt4 could not be observed by
      NMR titration experiments. A conserved glutamate residue, which was shown to be
      crucial for dimerization in yeast, is also involved in the human heterodimer, but
      is substituted for a glutamine residue in Escherichia coli NusG. However,
      exchanging the glutamine for glutamate proved not to be sufficient to induce
      hSpt4 binding.

PMID- 19860737
TI  - Pharmacological targeting of the Hsp70 chaperone.
AB  - The molecular chaperone, heat shock protein 70 (Hsp70), acts at multiple steps in
      a protein's life cycle, including during the processes of folding, trafficking,
      remodeling and degradation. To accomplish these various tasks, the activity of
      Hsp70 is shaped by a host of co-chaperones, which bind to the core chaperone and
      influence its functions. Genetic studies have strongly linked Hsp70 and its co
      chaperones to numerous diseases, including cancer, neurodegeneration and
      microbial pathogenesis, yet the potential of this chaperone as a therapeutic
      target remains largely underexplored. Here, we review the current state of Hsp70
      as a drug target, with a special emphasis on the important challenges and
      opportunities imposed by its co-chaperones, protein-protein interactions and
      allostery.

PMID- 19860742
TI  - Release of ATP from rat urinary bladder mucosa: role of acid, vanilloids and
      stretch.
AB  - BACKGROUND AND PURPOSE: ATP, released from urothelial cells, modulates afferent
      nerve firing from the urinary bladder. Here, we have characterized ATP release
      from the rat bladder mucosa in response to acid, capsaicin, electrical field
      stimulation (EFS) and stretch, using agonists and antagonists at transient
      receptor potential vanilloid receptor 1 (TRPV1) and acid-sensing ion channels
      (ASICs). EXPERIMENTAL APPROACH: Rat mucosal strips (containing urothelium and
      lamina propria) in Perspex microbaths were superfused with Krebs solution. ATP
      was measured after exposure of matched strips to acid (pH 6.6-5.0), capsaicin
      (0.1-10 microM), EFS or stretch (150% of original length). KEY RESULTS: Median
      basal ATP release was 3.46 nmol g(-1). The mucosal strips responded to stimuli
      with potency order (median, IQR): acid (pH 5.6-6.0) 286 (103-555) > 10 microM
      capsaicin 188 (117-431) > 10 Hz EFS 63.0 (13.3-96.4) > stretch 24.4 (6.73-55.1)
      nmol ATP g(-1). ATP release in response to acid was pH dependent (P < 0.05).
      Responses to capsaicin did not desensitize nor were they concentration dependent.
      TRPV1 antagonist, capsazepine (10 microM) abolished capsaicin-evoked ATP release,
      and reduced acid-evoked (pH 6.5) release to 30% (P < 0.001). The ASIC channel
      antagonists gadolinium (0.1 mM) and amiloride (0.3 microM) reduced (P < 0.05) the
      acid-evoked (pH 6.5) release to 40 and 6.5% respectively. ASIC (ASIC1, ASIC2a,
      ASIC2b, ASIC3) and two TRPV1 gene products were detected in mucosal and detrusor
      extracts. CONCLUSIONS AND IMPLICATIONS: Capsaicin (at TRPV1) and acid (at both
      TRPV1 and ASIC) induce ATP release from the rat bladder mucosa. This ATP appears
      to be principally of urothelial origin. This study highlights the importance of
      ATP and acid as signalling molecules in modulating bladder function.

PMID- 19860743
TI  - Effect of gene-environment Interactions on mental development in African
      American, Dominican, and Caucasian mothers and newborns.
AB  - The health impact of environmental toxins has gained increasing recognition over
      the years. Polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco
      smoke (ETS) are known to affect nervous system development in children, but no
      studies have investigated how polymorphisms in PAH metabolic genes affect child
      cognitive development following PAH exposure during pregnancy. In two parallel
      prospective cohort studies of non-smoking African American and Dominican mothers
      and children in New York City and of Caucasian mothers and children in Krakow,
      Poland, we explored the effect of gene-PAH interaction on child mental
      development index (MDI). Genes known to play important roles in the metabolic
      activation or detoxification of PAHs were selected. Genetic variations in these
      genes could influence susceptibility to adverse effects of PAHs in polluted air.
      We explored the effects of interactions between prenatal PAH exposure and 21
      polymorphisms or haplotypes in these genes on MDI at 12, 24, and 36 months among
      547 newborns and 806 mothers from three different ethnic groups. Significant
      interaction effects between haplotypes and PAHs were observed in mothers and
      their newborns in all three ethnic groups after Bonferroni correction. The
      strongest and most consistent effect observed was between PAH and haplotype
      ACCGGC of the CYP1B1 gene.

PMID- 19860745
TI  - Deeper problems for Noonan's probability argument against abortion: on a
      charitable reading of Noonan's conception criterion of humanity.
AB  - In 'An Almost Absolute Value in History' John T. Noonan criticizes several
      attempts to provide a criterion for when an entity deserves rights. These
      criteria, he argues are either arbitrary or lead to absurd consequence. Noonan
      proposes human conception as the criterion of rights, and justifies it by appeal
      to the sharp shift in probability, at conception, of becoming a being possessed
      of human reason. Conception, then, is when abortion becomes immoral. The article
      has an historical and a philosophical goal. The historical goal is to carefully
      present the probability argument in a charitable manner. The philosophical goal
      is to offer a unique criticism of Noonan's probability argument against abortion.
      I argue that, even on a very charitable reading of Noonan's argument for the
      conception criterion, this criterion is also susceptible to charges of
      arbitrariness and absurdity. Noonan's claim that probability shifts have anything
      to do with the moral rights of fetuses cannot be made coherent. I also show that
      there are problems with Noonan's assumptions about moral rights and the potential
      to become a being possessed of human reason.

PMID- 19860744
TI  - Allergic women show reduced T helper type 1 alloresponses to fetal human
      leucocyte antigen mismatch during pregnancy.
AB  - Low-level alloreactivity between mother and fetus may provide stimulation for
      fetal T helper type 1 (Th1) cell immune maturation. This study explored the
      effects of human leucocyte antigen (HLA) mismatch on materno-fetal interactions
      detected as cytokine responses and lymphoproliferation in mixed lymphocyte
      reactions, and whether this was altered in allergic women (n = 62) who have a Th2
      propensity compared with non-allergic women (n = 65). HLA-DRbeta1 mismatch was
      associated with significantly increased Th1 interferon (IFN)-gamma, Th2
      interleukin (IL)-13 and lymphoproliferative responses by both mothers and
      fetuses. Allergic women showed significantly lower IFN-gamma Th1 production in
      response to HLA-DRbeta1 mismatch. The infants of these women also showed
      significantly lower IL-10 and lower IFN-gamma production relative to IL-13. Both
      HLA-DRbeta1 mismatch and maternal allergy had significant independent effects on
      maternal IFN-gamma Th1 responses. Maternal allergy modifies HLA-mediated
      alloreactivity between the mother and the fetus, reducing Th1 activation. This
      may affect the cytokine milieu at the materno-fetal interface and could be
      implicated in the attenuated Th1 responses observed commonly in infants of atopic
      mothers.

PMID- 19860746
TI  - Current functions of Italian ethics committees: a cross-sectional study.
AB  - BACKGROUND: The rapid pace of progress in medical research, the consequent need
      for the timely transfer of new knowledge into practice, and the increasing need
      for ethics support, is making the work of Ethics Committees (ECs) ever more
      complex and demanding. As a response, ECs in many countries exhibit large
      variation in number, mandate, organization and member competences. This cross
      sectional study aims to give an overview of the different types of activities of
      Italian ECs and favour discussion at a European level. METHODS: A questionnaire
      was emailed to all Italian Ethics Committees contained in the national Registry
      of the Ministry of Health, enquiring whether the EC was conducting, or planning
      to conduct, 4 specific activities. A telephone interview was conducted to
      determine reasons for failure to respond. RESULTS: Response rate was 53% (101
      respondents out of 191). 20% of ECs restrict their responsibilities to research
      protocol review, 25% also offer ethical consultation to institutions, support on
      individual health care decisions and promotes educational initiatives, while the
      remaining 50% conduct a few of the examined activities to varying degrees. Large
      variation was observed across different types of hosting institutions and
      geographical locations. CONCLUSIONS: A common European model should be developed,
      defining EC functions, member selection modalities, necessary member competences,
      decision-making criteria and measures for work verification. In the absence of
      sound empirical evidence, it would be interesting to study the effectiveness and
      efficiency of the different existing models.

PMID- 19860747
TI  - The dead donor rule, voluntary active euthanasia, and capital punishment.
AB  - We argue that the dead donor rule, which states that multiple vital organs should
      only be taken from dead patients, is justified neither in principle nor in
      practice. We use a thought experiment and a guiding assumption in the literature
      about the justification of moral principles to undermine the theoretical
      justification for the rule. We then offer two real world analogues to this
      thought experiment, voluntary active euthanasia and capital punishment, and argue
      that the moral permissibility of terminating any patient through the removal of
      vital organs cannot turn on whether or not the practice violates the dead donor
      rule. Next, we consider practical justifications for the dead donor rule.
      Specifically, we consider whether there are compelling reasons to promulgate the
      rule even though its corresponding moral principle is not theoretically
      justified. We argue that there are no such reasons. In fact, we argue that
      promulgating the rule may actually decrease public trust in organ procurement
      procedures and medical institutions generally - even in states that do not permit
      capital punishment or voluntary active euthanasia. Finally, we examine our case
      against the dead donor rule in the light of common arguments for it. We find that
      these arguments are often misplaced - they do not support the dead donor rule.
      Instead, they support the quite different rule that patients should not be killed
      for their vital organs.

PMID- 19860748
TI  - Tissue distribution of p-glycoprotein in cats.
AB  - Permeability glycoprotein (P-gp) is a membrane-bound efflux pump that exports
      various substances out of the cell. Variations in P-gp expression play an
      important role in susceptibility to toxic substances, drug efficacy and disease
      risk. In the present study, the distribution of the MDR1-gene product P-gp was
      determined in normal tissues of domestic shorthair cats using
      immunohistochemistry. Two monoclonal antibodies C494 and C219 were used,
      recognizing a different epitope on the human P-gp molecule. A consistent positive
      immunolabelling was obtained. The tissue distribution and cellular locations with
      antibody C494 were similar to those in man and dogs; with liver, colon, adrenal
      cortex and brain capillaries being consistently and intensely labelled. However,
      the immunolabelling in the kidney was in contradiction to man and dogs. The C219
      antibody seems to react with a specific form of P-gp, only expressed in feline
      tissues with a barrier function, i.e. endothelia of the brain, testes and
      ovaries, and intestinal epithelial cells in contact with the lumen.

PMID- 19860749
TI  - Transient neurological symptoms after spinal anaesthesia with levobupivacaine 5
      mg/ml or lidocaine 20 mg/ml.
AB  - BACKGROUND: Transient neurological symptoms (TNS) after spinal anaesthesia have
      been reported most commonly in association with lidocaine, but have been observed
      with other local anaesthetics. The aim of this prospective, randomized, double
      blind study was to investigate the incidence of TNS after spinal anaesthesia with
      either levobupivacaine or lidocaine. METHODS: Patients undergoing inguinal
      hernia, appendectomy, varicose vein or minor orthopaedic operations were included
      in the study (60 patients; 47 male, 13 female, overall mean age 30 years). All
      patients had an American Society of Anesthesiologists score of I or II. The
      patients were randomly assigned to receive spinal anaesthesia with either 20 mg
      isobaric levobupivacaine (5 mg/ml) or 80 mg isobaric lidocaine (20 mg/ml). Onset
      of sensory and motor block and side effects were recorded. On post-operative days
      1, 2, and 3, patients were interviewed by an investigator blinded to the spinal
      anaesthetic used. The patients were classified as having TNS if, following
      recovery from anaesthesia, there was pain in the buttocks, thighs and/or lower
      limbs. RESULTS: In the levobupivacaine group, one patient (3.33%) experienced
      TNS, whereas in the lidocaine group, eight (26.6%) experienced TNS (P=0.002).
      Maximum times to arrival of sensory blocks were shorter with lidocaine (P<0.001).
      The levobupivacaine and lidocaine groups did not differ significantly in terms of
      the highest dermatome included in sensory block or motor block grade. CONCLUSION:
      After spinal anaesthesia with levobupivacaine, the incidence of TNS was much less
      than after lidocaine. However, it appears that TNS may occur in association with
      levobupivacaine.

PMID- 19860750
TI  - Postoperative impact of regular tobacco use, smoking or snuffing, a prospective
      multi-center study.
AB  - BACKGROUND: The aim was to study the effects of different tobacco administration
      routes on pain and post-operative nausea and vomiting (PONV), following three
      common day surgical procedures: cosmetic breast augmentation (CBA), inguinal
      hernia repair (IHR) and arthroscopic procedures (AS). We have prospectively
      investigated the effects of regular tobacco use in ambulatory surgery. METHODS:
      The 355 allocated patients were followed during recovery and the first day at
      home. RESULTS: Thirty-two percent of the patients used tobacco regularly, 33% of
      CBA, 27% of IHR and 34% of AS. Pain was well controlled in the post-anesthesia
      care unit at rest; during ambulation, 37% of all patients reported VAS>3. Tobacco
      use had no impact on early post-operative pain. Post-operative nausea was
      experienced by 30% of patients during recovery while in hospital. On day 1, 14%
      experienced nausea. We found a significant reduction of PONV among tobacco users
      (smoking and/or snuffing). Smoking or snuffing reduced the risk of PONV by nearly
      50% in both genders on the day of surgery and at the first day at home. The
      reduction of PONV was equal, regardless of tobacco administration routes.
      CONCLUSION: We found that regular use of tobacco, both by smoking and snuffing,
      had a significant effect on PONV during the early post-operative period. Non
      tobacco users undergoing breast surgery were found to have the highest risk for
      PONV. We could not see any influence of nicotine use on post-operative pain.
      Thus, it seems of value to identify regular tobacco use, not only smoking, as a
      part of the pre-operative risk assessment.

PMID- 19860751
TI  - Neuroprotective effects of a combination of dexmedetomidine and hypothermia after
      incomplete cerebral ischemia in rats.
AB  - BACKGROUND: Dexmedetomidine and hypothermia are known to reduce neuronal injury
      following cerebral ischemia. We examined whether a combination of dexmedetomidine
      and hypothermia reduces brain injury after transient forebrain ischemia in rats
      to a greater extent than either treatment alone. METHODS: Thirty-eight male
      Sprague-Dawley rats were anesthetized with fentanyl and nitrous oxide in oxygen.
      Four groups were tested: group C (saline 1 ml/kg, temporal muscle temperature
      37.5 degrees C); group H (saline 1 ml/kg, 35.0 degrees C); group D
      (dexmedetomidine 100 microg/kg, 37.5 degrees C); and group DH (dexmedetomidine
      100 microg/kg, 35.0 degrees C). Dexmedetomidine or saline was administered
      intraperitoneally 30 min before ischemia. Cerebral ischemia was produced by right
      carotid artery ligation with hemorrhagic hypotension (mean arterial pressure 40
      mmHg) for 20 min. Neurologic outcome was evaluated at 24, 48, and 72 h after
      ischemia. Histopathology was evaluated in the caudate and hippocampus at 72 h
      after ischemia. RESULTS: Neurologic outcome was significantly better in the group
      DH than the group C (P<0.05), whereas it was similar between the group DH and the
      groups D or H. Survival rate of the hippocampal CA1 neurons was significantly
      greater in groups D, H, and DH than group C (P<0.05). Histopathologic injury in
      the caudate section was significantly less in groups H and DH than group C
      (P<0.05). CONCLUSION: The combination of dexmedetomidine and hypothermia improved
      short-term neurologic outcome compared with the control group, whereas the
      combination therapy provided comparable neuroprotection with either of the two
      therapies alone.

PMID- 19860752
TI  - Successful rotational thromboelastometry-guided treatment of traumatic
      haemorrhage, hyperfibrinolysis and coagulopathy.
AB  - Transfusion of allogeneic blood products is associated with increased morbidity
      and mortality. Therefore, strategies for reducing transfusion of these products
      during trauma management are valuable. We report a case of severe blunt abdominal
      trauma, successfully treated with antifibrinolytic medication and fibrinogen
      concentrate. Rotational thromboelastometry (ROTEM) was used to identify
      hyperfibrinolysis and afibrinogenaemia. In order to achieve haemostasis, over a 3
      h period, the patient received a total of 1 g of tranexamic acid, 7 U of packed
      red blood cells, 16 g of fibrinogen concentrate (Haemocomplettan P), 3500 ml of
      colloids and 5500 ml of lactated Ringer's solution. Together with surgical
      measures, this treatment stopped the bleeding and stabilised the patient. There
      was no transfusion of either fresh-frozen plasma or platelets. The limited need
      for allogeneic blood products is of particular interest, and clinical studies of
      the approach used here appear to be warranted.

PMID- 19860753
TI  - Risk of pulmonary aspiration with laryngeal mask airway and tracheal tube:
      analysis on 65 712 procedures with positive pressure ventilation.
AB  - We compared the risk of pulmonary aspiration in patients whose lungs were
      mechanically ventilated through a laryngeal mask airway (35 630 procedures) or
      tracheal tube (30 082 procedures). Three cases of pulmonary aspiration occurred
      with the laryngeal mask airway and seven with the tracheal tube. There were no
      deaths related to pulmonary aspiration. The incidence and outcome of pulmonary
      aspiration detected in this study were similar to those previously reported. The
      adjusted odds ratio (OR) for pulmonary aspiration with the laryngeal mask airway
      was 1.06 (95% CI 0.20-5.62). Unplanned surgery (OR 30.5, 95% CI 8.6-108.9) and
      male sex (OR 8.6, 95% CI 1.1-68) were associated with an increased risk of
      aspiration and age < 14 years with a reduced risk (OR 0.21, 95% CI 0.07-0.64).
      There were contraindications and exclusions to the use of the laryngeal mask
      airway but in this selected population the use of an laryngeal mask airway was
      not associated with an increased risk of pulmonary aspiration compared with a
      tracheal tube.

PMID- 19860755
TI  - The jewel of India.

PMID- 19860754
TI  - An assessment of the validity of SOFA score based triage in H1N1 critically ill
      patients during an influenza pandemic.
AB  - Sequential Organ Failure Assessment (SOFA) score based triage of influenza A H1N1
      critically ill patients has been proposed for surge capacity management as a
      guide for clinical decision making. We conducted a retrospective records review
      and SOFA scoring of critically ill patients with influenza A H1N1 in a mixed
      medical-surgical intensive care unit in an urban hospital. Eight critically ill
      patients with influenza A H1N1 were admitted to the intensive care unit. Their
      mean (range) age was 39 (26-52) years with a length of stay of 11 (3-17) days.
      All patients met SOFA score based triage admission criteria with a modal SOFA
      score of five. Five patients required invasive ventilation for a mean (range) of
      5 (4-11) days. Five patients would have been considered for withdrawal of
      treatment using SOFA scoring guidelines at 48 h. All patients survived. We
      conclude that SOFA score based triage could lead to withdrawal of life support in
      critically ill patients who could survive with an acceptably low length of stay
      in the intensive care unit.

PMID- 19860757
TI  - M3 muscarinic receptor expression on suburothelial interstitial cells.

PMID- 19860758
TI  - Surgery illustrated--focus on details--anterior suspension of the dorsal vein
      complex and fixation of the anterior fibromuscular stroma during laparoscopic
      prostatectomy for facilitating early continence.

PMID- 19860763
TI  - Abstracts of the 12th European AIDS Conference/EACS, 11-14 November 2009,
      Cologne, Germany.

PMID- 19860762
TI  - Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg
      for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind,
      randomized, placebo-controlled study.
AB  - BACKGROUND: Bilastine is a novel nonsedative H(1)-receptor antagonist, which may
      be used for the symptomatic treatment of chronic idiopathic urticaria (CU). The
      aim of this study was to compare the clinical efficacy and safety of bilastine 20
      mg vs levocetirizine 5 mg and placebo in CU patients with moderate-to-severe
      symptoms. METHODS: Overall 525 male and female subjects aged 18-70 years were
      randomized to receive bilastine 20 mg, levocetirizine 5 mg or placebo, once daily
      for 28 days, in double-blind manner, in 46 centres across Europe and Argentina.
      Patients rated symptoms of pruritus, number of wheals, and maximum size of wheals
      (on predefined scales) as reflective (over past 12 h) symptoms twice daily, for
      assessment of change from baseline in the total symptoms scores (TSS) over 28
      days as the primary efficacy measure. Changes in reflective and instantaneous
      symptoms scores, Dermatology Life Quality Index (DLQI), and CU-associated
      discomfort and sleep disturbance were assessed as secondary outcomes. Safety was
      assessed according to adverse events, laboratory tests and electrocardiograms.
      RESULTS: Bilastine reduced patients' mean reflective and instantaneous TSS from
      baseline to a significantly greater degree than placebo (P < 0.001); from day 2
      onwards of treatment. The DLQI, general discomfort, and sleep disruption were
      also improved significantly in bilastine-treated patients as compared with
      placebo-treated patients (P < 0.001 for all parameters). Comparison with
      levocetirizine indicated both treatments to be equally efficacious as well as
      equally safe and well tolerated as compared with placebo. CONCLUSIONS: Bilastine
      20 mg is a novel effective and safe treatment option for the management of CU.

PMID- 19860767
TI  - Genetic cardiovascular risk factors and age-related macular degeneration.
AB  - PURPOSE: To investigate the association between genetic cardiovascular risk
      factors and exudative age-related macular degeneration (AMD) in a White Austrian
      population. METHODS: Seventy-five unrelated AMD patients and 75 unrelated
      healthy, sex- and age-matched control patients were genotyped for the following
      19 single nucleotide polymorphisms (SNPs) in 14 different genes: blood
      coagulation factor V (FV) R506Q, factor II (prothrombin) G20210A and factor XIII
      (FXIII) V34L; 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C;
      plasminogen activator inhibitor 1 (PAI-1) 4G/5G; endothelial protein C receptor
      (EPCR) 4600 A>G (A3 haplotype), 4678 G>C (A1 haplotype); apolipoprotein B (ApoB)
      R3500Q; apolipoprotein E (ApoE) E2/E3/E4; beta-fibrinogen -455 G>A; human
      platelet antigen 1 (HPA1) a/b; angiotensin-converting enzyme (ACE) I/D;
      endothelial nitric oxide synthase (eNOS) 786 T>C, 894 G>T; lymphotoxin alpha
      (LTA) 804 C>A and 9p21 rs10757278. Genotyping was carried out by polymerase chain
      reaction (PCR) followed by reverse hybridization (CVD StripAssays; ViennaLab
      Diagnostics, Vienna, Austria). RESULTS: No statistically significant association
      could be observed between AMD and the investigated genetic risk factors for
      cardiovascular disease (CVD). All factors seem to be uniformly distributed in the
      two groups of AMD patients and healthy controls. Two variables -beta-fibrinogen: 
      455 G>A (p = 0.0786) and apolipoprotein E4 (p = 0.0636) - were not as far from
      association as the others. CONCLUSION: Our data show that the 19 tested CVD risk
      markers do not play a significant role in AMD. beta-Fibrinogen and apolipoprotein
      E4 should be examined in a larger cohort.

PMID- 19860768
TI  - Reduced corneal sensitivity in patients with primary Sjogren's syndrome.

PMID- 19860769
TI  - Descending doses of intravitreal bevacizumab for the regression of diabetic
      neovascularization.
AB  - PURPOSE: To report short-term regression of neovascularization after varying
      intravitreal doses of bevacizumab (Avastin(r); Genentech, San Francisco,
      California, USA) in patients with proliferative diabetic retinopathy (PDR).
      METHODS: Eighty eyes from 76 patients with active neovascularization of the disc
      (NVD) or elsewhere (NVE) caused by PDR were divided into four groups and treated
      with a single intravitreal bevacizumab (IVB) injection of 1.25 mg, 600 MUg, 300
      MUg or 150 MUg, respectively. All patients underwent ophthalmoscopic examination
      and fluorescein angiography at baseline, 1 week, 1 month and 2 months later.
      RESULTS: No significant ocular or systemic adverse events were observed. In all
      patients with NVD or NVE, complete resolution of leakage was recorded within the
      first week or the first month of the injection. Even with the lowest dose (150
      MUg), regression of neovascularization appeared as early as the first week and
      lasted for over a month. Recurrence of fluorescein leakage was observed in all
      groups after the first month and did not correlate with the extent of
      neovascularization or IVB dose. CONCLUSION: Short-term results suggest that IVB
      given below the standard dosage (150-300 MUg compared to 1.25 mg) can lead to the
      achievement of complete regression of diabetic retinal neovascularization within
      30-45 days of injection.

PMID- 19860770
TI  - Vasoproliferative retinal tumours in a Swedish population.
AB  - PURPOSE: To describe the clinical appearance and the visual outcome of a cohort
      of patients with vasoproliferative retinal tumours (VPRTs) that were diagnosed
      and treated between 2002 and 2007 at the University Hospital of Orebro. METHODS:
      Nine patients with diagnosed VPRTs were included in a retrospective study. The
      mean age at the time of diagnosis was 50.2 years (range 7-74 years). Follow-up
      time ranged between 14 and 83 months (mean 42.6). Nine out of ten eyes received
      cryotherapy; six eyes were also treated with photocoagulation. One patient was
      treated with intravitreal injections of ranibizumab (Lucentis((r))) and another
      was referred for brachytherapy. Because of persisting macular oedema, one eye was
      treated with intravitreal injection of triamcinolon. RESULTS: Of the treated
      eyes, one had anterior uveitis, six had macular oedema at baseline and four had
      an exudative retinal detachment at the time of diagnosis. Seven eyes underwent
      vitrectomy because of epiretinal membranes. Visual acuity at diagnosis was 0.21
      (mean) (range 0.02-0.6) and at latest check-up 0.30 (mean) (range light
      perception (LP)-1.0), with improvement in six eyes and deterioration in two. Two
      out of four patients with retinal detachment were successfully treated
      surgically. CONCLUSION: VPRTs are benign intraretinal changes. Several
      complications are associated with this condition. All patients in this study had
      symptom-giving tumours and six patients (six eyes) already had profound macular
      oedema at presentation. In these cases, when complications have already
      developed, the final visual prognosis is poor, thereby making it important to
      detect these tumours early. The patient who received anti-vascular endothelial
      growth factor (VEGF; Lucentis) therapy showed a slow improvement and distinct
      regression in exudations during the follow-up time. However, no increase in
      visual acuity was seen. At latest examination a peripheral exudative retinal
      detachment was still observed. Whether anti-VEGF treatment is effective, as
      either an alternative or complementary therapy, must be established in the
      future.

PMID- 19860771
TI  - Outcome after paediatric cataract surgery in otherwise healthy children.

PMID- 19860772
TI  - Pupilloplasty for congenital pupillary-iris-lens membrane with 25-gauge vitreous
      cutter.

PMID- 19860773
TI  - Asymmetry of diurnal intraocular pressure fluctuation between right and left
      eyes.
AB  - PURPOSE: To evaluate diurnal curves of intraocular pressure (IOP) in the right
      and left eyes of non-glaucomatous patients. METHODS: We measured IOP during
      waking hours and in habitual positions in 102 non-glaucomatous patients every 2
      hr between 09.00 hr and 23.00 hr using a Goldman applanation tonometer.
      Individual factors and biometries were measured and associated with diurnal IOP
      variations. RESULTS: There was no significant difference in IOP variation between
      the right and left eyes over eight time-points (repeated measure anova, P =
      0.995). The mean coefficient of IOP in the right and left eyes at the eight time
      points ranged from 0.806 to 0.887. Forty-one (40.2%), 15 (14.7%) and five (4.9%)
      patients showed at least one asymmetrical IOP variation over seven time intervals
      at the cut-off value >= 2, >= 3 and > 3 mmHg, respectively. Mean incidence of
      asymmetrical IOP variation was 10.9 +/- 1.6% at >= 2 mmHg, 2.9 +/- 0.8% at >= 3
      mmHg and 0.8 +/- 0.4% at > 3 mmHg. Age, differences in anterior chamber depth,
      lens thickness and axial length showed several significant associations with the
      incidence of asymmetrical IOP variation. CONCLUSION: Diurnal variation of IOP
      showed asymmetry between right and left eyes in patients without glaucoma. Ageing
      and differences in local ocular factors between bilateral eyes may affect the
      incidence of asymmetrical IOP variation.

PMID- 19860776
TI  - Subjective visual sensations during cataract surgery under topical anaesthesia.

PMID- 19860774
TI  - Efficacy of 12-month treatment of neovascular age-related macular degeneration
      with intravitreal bevacizumab based on individually determined injection
      strategies after three consecutive monthly injections.
AB  - PURPOSE: To report the results of intravitreal treatment with bevacizumab in
      neovascular age-related macular degeneration (AMD) after a loading dose (LD) of
      three monthly injections followed by an optical coherence tomography (OCT)-guided
      strategy, based on best-corrected visual acuity (VA) and number of injections
      required over 1 year. METHODS: A series of consecutive cases of 149 eyes of 147
      patients received three or more intravitreal injections of bevacizumab (1.25 mg)
      for neovascular AMD over a 1-year period. The patients underwent ophthalmological
      examinations: measurement of the VA, fluorescein angiography, dilated fundus
      examination at baseline; VA, OCT and dilated fundus examination at monthly follow
      up visits. Repeated injections were given each month for the first 3 months (LD);
      thereafter, injections were only administered if leakage or macular oedema were
      present. RESULTS: Mean baseline VA was 51 +/- 14 letters, which improved to 58 +/
      15 letters (p < 0.0001; n = 149) at first evaluation (15 +/- 2 weeks), 59 +/- 15
      letters (p < 0.0001; n = 143) at second evaluation (25 +/- 2 weeks) and 57 +/- 16
      letters (p < 0.0001; n = 132) at third evaluation (51 +/- 3 weeks). The baseline
      mean central retinal thickness (344.6 MUm) and total macular volume (8.6 mm(3) )
      decreased at first evaluation, to 219.0 MUm (p < 0.0001) and 7.2 mm(3) (p <
      0.0001), respectively. The mean number of injections per patient treated for 1
      year was 5.1 (range 3-9). No systemic side-effects were noted. CONCLUSION:
      Treatment of neovascular AMD with intravitreal bevacizumab administered in LD of
      three monthly injections and followed by an OCT-guided strategy provides
      functional and anatomical improvements for up to 1 year.

PMID- 19860777
TI  - Effects of 7-methylxanthine on the sclera in form deprivation myopia in guinea
      pigs.
AB  - PURPOSE: The aim of this study was to determine the effect of the adenosine
      receptor antagonist 7-methylxanthine (7-MX) on form deprivation myopia in 3-week
      old guinea pigs. METHODS: Two groups of 3-week-old guinea pigs were subjected to
      monocular deprivation (MD) using a diffuser and fed either 7-MX (300 mg/kg body
      weight; n = 7) or vehicle control (saline at an equal volume to 7-MX; n = 7). A
      control group (n = 6) was not subjected to form deprivation. Ocular refraction,
      axial length and body weight were measured at the start and after 21 days. The
      thickness of the posterior sclera was measured by light microscopy and the
      collagen fibril diameter in the inner, middle and outer layers of the sclera was
      measured by electron microscopy. RESULTS: In the vehicle control group, 21 days
      of MD produced significant amounts of myopia, axial elongation, thinning of the
      posterior sclera and thinning of the median collagen fibril diameter in the
      posterior sclera relative to the contralateral eyes. In the guinea pigs fed with
      7-MX, however, form deprivation produced significantly less myopia and axial
      elongation compared with vehicle control animals. The 7-MX-treated animals
      exhibited a thickening of the posterior sclera in both the MD eye and the
      contralateral eye. In the 7-MX-treated animals, the median collagen fibril
      diameter in the posterior sclera was not reduced by form deprivation.
      CONCLUSIONS: Treatment with 7-MX appears to not only decrease the amount of
      myopia by around 50% and eliminate the eye elongation induced by form deprivation
      in guinea pigs, but also to prevent form deprivation myopia-related scleral
      changes, such as thinning of the sclera and thinning of the collagen fibril
      diameter in the posterior sclera.

PMID- 19860778
TI  - Non-contact in vivo confocal scanning laser microscopy in exfoliation syndrome,
      exfoliation syndrome suspect and normal eyes.
AB  - PURPOSE: This study aimed to evaluate the efficacy of non-contact confocal laser
      microscopy in detecting structural alterations of the cornea, iris and lens in
      fellow eyes of patients with clinically unilateral exfoliation syndrome (XFS) and
      XFS suspects. METHODS: In a prospective observational case series, eyes of 12
      patients with clinically unilateral XFS, six XFS suspects and six age-matched
      controls were divided into four groups. Group A included eyes with clinically
      visible exfoliation material (XFM) on the pupillary border or anterior lens
      capsule (n = 12); group B included fellow eyes of clinically unilateral XFS
      patients without visible XFM (n = 12); group C comprised eyes in XFS suspects
      with signs of pigment dispersion without visible XFM (n = 10), and group D
      consisted of control eyes with no evidence of XFM or pigment dispersion (n = 12).
      The cornea, iris and lens were imaged using a non-contact lens prototype for the
      Rostock Cornea Module (HRT II). Images were analysed by two observers masked to
      the clinical findings. RESULTS: Visible XFM (group A) on the lens capsule was
      characterized by hyperreflectivity in the granular and central disc areas and
      hyporeflective spaces in the intermediate zones. Similar hyperreflectivity was
      noted in four of 12 and one of 10 eyes in groups B and C, respectively, but in
      none in group D. Corneal endothelial hyperreflective deposits were found in eight
      of 12, four of 12 and one of 10 eyes in groups A, B and C, respectively, and no
      eyes in group D. CONCLUSIONS: This technology permits visualization of XFM and /
      or XFMrelated changes in the cornea and lens in the unaffected eyes of patients
      with clinically unilateral XFS. It may allow early detection of XFS and impact
      glaucoma screening and clinical surveillance decisions.

PMID- 19860779
TI  - Ocular blood flow assessment using continuous laser Doppler flowmetry.
AB  - This article describes the technique of continuous laser Doppler flowmetry (LDF)
      as applied to the measurement of the flux of red blood cells in the optic nerve
      head, iris and subfoveal choroid. Starting with the exposition of the physical
      principles underlying LDF, we first describe the various devices developed to
      perform LDF in these vascular beds. We then discuss the clinical protocols, blood
      flow parameters, calibration procedures, reproducibility and limitations of the
      LDF technique. Various problems still need to be solved in order to bring to
      light the full potential of LDF in the assessment of microcirculatory
      haemodynamics.

PMID- 19860780
TI  - Alterations in anterior chamber depth in primary open-angle glaucoma patients
      during latanoprost therapy.
AB  - PURPOSE: The aim of this study was to evaluate changes in the anterior chamber
      depth (ACD) in primary open-angle glaucoma (POAG) patients during latanoprost
      therapy. METHODS: We carried out a prospective study in which we enrolled 66
      newly diagnosed POAG patients treated with latanoprost 0.005% (group 1) and 50
      ocular hypertensive and / or glaucoma suspect cases who were given no therapy
      (group 2 [control]). Measurements of the ACD were performed by A-scan
      ultrasonography before and after cycloplegia at baseline and at 3 months of
      latanoprost therapy. Differences in ACD and their correlations with the ocular
      hypotensive effect of the agent as well as the clinical significance of changes
      in ACD were analysed using Student's t-test and Pearson's correlation
      coefficient. Statistical significance was set at p < 0.05. RESULTS: Mean baseline
      ACD was 3.13 +/- 0.35 mm (range 2.45-3.84 mm) in group 1 and 3.14 +/- 0.36 mm
      (range 2.54-3.80 mm) in group 2 (p = 0.89). At 1 hour after instillation of
      cyclopentolate 1%, mean ACD in groups 1 and 2 was 3.18 +/- 0.38 mm (range 2.45
      3.92 mm) and 3.19 +/- 0.37 mm (range 2.56-3.91 mm), respectively (p = 0.91).
      After 3 months of treatment, mean ACD in group 1 both without (3.05 +/- 0.36 mm,
      range 2.14-3.76 mm) and with (3.09 +/- 0.4 mm, range 2.20-3.96 mm) cycloplegia
      was significantly reduced compared with baseline values (p < 0.001 for both).
      However, there was no significant difference between mean ACD at baseline and
      that at month 3 in group 2. No correlation was demonstrated between the changes
      in ACD and the ocular hypotensive effect of latanoprost (p = 0.96, r = - 0.006).
      There were no changes in refractive status or visual acuity. CONCLUSIONS: The
      overall results seem to suggest that latanoprost decreases mean ACD in patients
      with POAG. The clinical significance of this effect is uncertain.

PMID- 19860781
TI  - Longterm follow-up of pars plana vitrectomy for vitreous floaters: complications,
      outcomes and patient satisfaction.
AB  - PURPOSE: Floaters caused by degenerative or postoperative changes in the vitreous
      can interfere with all aspects of visual functioning. The aim of this study is to
      report the longterm outcome of pars plana vitrectomy (PPV) for persistent
      vitreous opacities. METHODS: In a retrospective, non-randomized, interventional
      case study we reviewed all cases of vitreous floaters that were vitrectomized at
      our department between 1997 and 2006. Patient complaints and satisfaction were
      assessed by a questionnaire administered at the end of follow-up. RESULTS:
      Seventy-three consecutive cases were included (61 patients). Mean Snellen best
      corrected visual acuity (BCVA) before surgery was 0.81. Overall, 85% of patients
      complained of severe or very severe difficulty caused by floaters. A total of 42%
      of eyes were pseudophakic, four of which were operated with combined PPV and
      phacoemulsification. Mean follow-up time was 37 months. Of the phakic eyes, 60%
      were operated for cataract during follow-up. One retinal detachment (RD) occurred
      immediately postoperatively (1.3%) and another four eyes developed RD during
      longterm follow-up 24-44 months after PPV (5.5% of cases). Postoperative BCVA
      remained mostly unchanged. Overall, 88% of patients were satisfied with the
      results of the operation. CONCLUSIONS: Some patients make considerable complaints
      as a result of vitreous opacities and their distress does not correlate with
      visual acuity. Vitrectomy is a safe and effective procedure with which to help
      these patients. Patients should be informed about the risk of cataract
      progression, unexpected inflammatory reaction and an increased risk for RD
      several years after PPV (5.5%).

PMID- 19860782
TI  - Intravitreal bevacizumab for choroidal neovascularization secondary to
      inflammation.

PMID- 19860783
TI  - Changes in macular sensitivity after reduced fluence photodynamic therapy
      combined with intravitreal triamcinolone.
AB  - PURPOSE: This study aimed to evaluate the course of macular sensitivity (MS)
      following treatment with reduced fluence photodynamic therapy (RPDT) versus
      standard photodynamic therapy (SPDT) in combination with intravitreal
      triamcinolone acetonide (IVTA) in patients with neovascular age-related macular
      degeneration, and to investigate the correlation between MS and angiographic
      outcomes. METHODS: Forty eyes in 40 patients were included in this prospective,
      randomized clinical study. Group 1 patients received RPDT (n = 20, light dose of
      25 J/cm(2) at 300 mW/cm(2)); group 2 patients received SPDT (n = 20, light dose
      of 50 J/cm(2) at 600 mW/cm(2)). All patients received 4 mg IVTA administered on
      the same day as RPDT or SPDT. Microperimetry, visual acuity testing (ETDRS) and
      fluorescein angiography (FA) were performed at baseline, and at months 3, 6, 9
      and 12. Main outcome parameters were mean differential light threshold (DLT), and
      absolute and relative scotoma size. RESULTS: Mean DLT decreased from 4.71 dB at
      baseline to 3.45 dB after 12 months in the SPDT + IVTA group (mean decrease 1.26
      dB; p > 0.05) and from 5.42 dB to 4.92 dB in the RPDT + IVTA group (mean decrease
      0.5 dB; p > 0.05). Absolute and relative scotoma sizes remained stable in both
      groups at 12 months (mean change 0 and -0.6 test-points; p > 0.05). Mean DLT
      values and absolute scotoma sizes correlated well with early and late leakage
      areas in FA (r = -0.45 to -0.80, p < 0.02). CONCLUSIONS: With regard to MS, RPDT
      + IVTA did not show significant benefits over SPDT + IVTA at 12 months. Macular
      sensitivity correlated well with angiographic outcomes.

PMID- 19860784
TI  - Persistent visual loss in malignant idiopathic intracranial hypertension.

PMID- 19860786
TI  - Food allergen labelling and consumer confusion.

PMID- 19860785
TI  - Day 1 postoperative intraocular pressure spike in vitreoretinal surgery (VDOP1).
AB  - PURPOSE: To classify the clinical characteristics that might identify patients
      who may not require next-day follow-up following routine vitreoretinal
      intervention. METHODS: Prospective case series. RESULTS: The only statistically
      significant factors for raised intraocular pressure (IOP) were gas tamponade and
      preoperative raised IOP. 44.7% (17/38) of patients with preoperative IOP >= 20
      mmHg had postoperative IOP >= 30 mmHg while 8.6% (17/197) of patients with
      preoperative IOP < 20 mmHg had postoperative IOP >= 30 mmHg (p = 0.0001).
      Phacoemulsification did not increase risk for a postoperative IOP spike. There
      was a 20-21% risk of postoperative IOP > 30 mmHg for patients with gas tamponade.
      All patients with no tamponade with IOP > 30 mmHg had preoperative IOP >= 20
      mmHg. CONCLUSION: Uncomplicated vitreoretinal procedures with preoperative IOP
      of< 20 mmHg and no gas tamponade are unlikely to have uncontrolled IOP spike at
      day 1.

PMID- 19860787
TI  - Food-dependent exercise-induced anaphylaxis in the celery-mugwort-birch-spice
      syndrome.

PMID- 19860788
TI  - The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN
      paper.
AB  - The methodology of randomized clinical trials is essential for the critical
      assessment and registration of therapeutic interventions. The CONSORT
      (Consolidated Standards of Reporting Trials) statement was developed to alleviate
      the problems arising from the inadequate reporting of randomized controlled
      trials. The present article reflects on the items that we believe should be
      included in the CONSORT checklist in the context of conducting and reporting
      trials in allergen-specific immunotherapy. Only randomized, blinded (in
      particular blinding of patients, health care providers, and outcome assessors),
      placebo-controlled Phase III studies in this article. Our analysis focuses on the
      definition of patients' inclusion and exclusion criteria, allergen
      standardization, primary, secondary and exploratory outcomes, reporting of
      adverse events and analysis.

PMID- 19860789
TI  - Major mite allergen Der f 1 concentration is reduced in buildings with improved
      energy performance.
AB  - BACKGROUND: Environmental conditions play a crucial role in mite growth, and
      optimal environmental control is key in the prevention of airway inflammation in
      chronic allergic rhinoconjunctivitis or asthma. OBJECTIVE: To evaluate the
      relationship between building energy performance and indoor mite allergen
      concentration in a cross-sectional study. METHODS: Major allergen concentration
      (Der f 1, Der p 1, mite group 2, Fel d 1 and Bla g 2) was determined by
      quantitative dot blot analysis from mattress and carpet dust samples in five
      buildings designed for low energy use (LEB) and in six control buildings (CB).
      Inhabitants had received 4 weeks prior to mite measurement a personal validated
      questionnaire related to the perceived state of health and comfort of living.
      RESULTS: Cumulative mite allergen concentration (with Der f 1 as the major
      contributor) was significantly lower in LEB as compared with CB both in
      mattresses and in carpets. In contrast, the two categories of buildings did not
      differ in Bla g 2 and Fel d 1 concentration, in the amount of dust and airborne
      mould collected. Whereas temperature was higher in LEB, relative humidity was
      significantly lower than in CB. Perceived overall comfort was better in LEB.
      CONCLUSIONS: Major mite allergen Der f 1 preferentially accumulates in buildings
      not specifically designed for low energy use, reaching levels at risk for
      sensitization. We hypothesize that controlled mechanical ventilation present in
      all audited LEB may favour lower air humidity and hence lower mite growth and
      allergen concentration, while preserving optimal perceived comfort.

PMID- 19860790
TI  - Determining the negative predictive value of provocation tests with beta-lactams.
AB  - BACKGROUND: The beta-lactam allergic work-up is mostly standardized. However, the
      negative predictive value of drug provocation tests is not yet well established.
      METHOD: A historical-prospective multicentre cohort study was conducted in four
      centres (one in France, one in Portugal, two in Italy) to assess the negative
      predictive value of provocation tests with beta-lactams in patients initially
      tested for a suspicion of drug allergy/hypersensitivity. Patients were contacted
      at least 6 months after the work-up, between 2003 and 2007. A new allergic work
      up was proposed to reacting patients. RESULTS: Among the 457 patients included,
      365 (79.9%) were followed up (159 [79.1%] from France, 153 [82.7%] from Italy and
      53 [74.6%] from Portugal). Only 118 (25.8%) were re-exposed to the negatively
      tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h
      after drug administration) reaction: five urticaria, three exanthema and one
      undefined cutaneous reaction. None were severe. Only four accepted a re
      challenge, negative in two cases and positive in the two others. The negative
      predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). CONCLUSION:
      Although the negative predictive value of drug provocation tests may not be 100%,
      none of the false negative patients experienced a life-threatening reaction. This
      should reassure doctors who might hesitate to prescribe beta-lactams, even in
      patients with negative allergic work-ups.

PMID- 19860791
TI  - Genetic evidence for a role of IL33 in nasal polyposis.
AB  - BACKGROUND: Little is known about the genetic factors that contribute to nasal
      polyposis (NP). A genome-wide association study identified 10 single nucleotide
      polymorphisms (SNPs) associated with eosinophilia. As eosinophils play a key role
      in the pathogenesis of NP, we assessed if any of these SNPs contribute to genetic
      susceptibility of NP. METHODS: We recruited 284 patients with NP in four
      participating hospitals in Belgium and 427 healthy controls, and genotyped 10
      SNPs affecting eosinophilia (rs1420101 in IL1RL1, rs12619285 in IKZF2, rs4431128
      in GATA2, rs4143832 in IL5, rs3184504 in SH2B3, rs2416257 in WDR36, rs2269426 in
      MHC, rs9494145 in MYB, rs748065 in GFRA2, and rs3939286 in IL33) using MALDI-TOF.
      A two-stage design was used while correcting for multiple testing. RESULTS: First
      stage analysis, involving 150 NP patients and 250 controls, identified rs3939286
      nearby IL33 as a susceptibility factor for NP. Per at-risk A-allele, rs3939286
      increased the risk for NP with an odds ratio (OR) of 1.60 (95% CI = 1.16-2.22; P
      = 0.0041). Second stage replication analysis in another 123 NP patients and 165
      controls confirmed this association (OR = 1.43; CI = 1.00-2.06; P = 0.046). The
      combined analysis of both stages revealed an OR of 1.53 (CI = 1.21-1.96; P =
      0.00041). Given the association of IL33 with NP, we also investigated rs1420101
      in IL1RL1, which is the receptor for IL33. Although rs1420101 itself failed to
      associate with NP, a combined risk assessment of rs3939286 and rs1420101 further
      increased the risk for NP. CONCLUSION: We provide unprecedented genetic evidence
      suggesting a role for the IL33 pathway in the pathogenesis of NP.

PMID- 19860792
TI  - Preservation of endothelium nitric oxide release by pulsatile flow
      cardiopulmonary bypass when compared with continuous flow.
AB  - The aim of this work is to analyze endothelium nitric oxide (NO) release in
      patients undergoing continuous or pulsatile flow cardiopulmonary bypass (CPB).
      Nine patients operated under continuous flow CPB, and nine patients on pulsatile
      flow CPB were enrolled. Plasma samples were withdrawn for the chemiluminescence
      detection of nitrite and nitrate. Moreover the cellular component was withdrawn
      for the detection of nitric oxide synthase (NOS) activity in the erythrocytes,
      and an estimation of systemic inflammatory response was carried out. Significant
      reduction in the intraoperative concentration with respect to the preoperative
      was observed only under continuous flow CPB for both nitrite and NO(x) (nitrite +
      nitrate) concentration (P = 0.010 and P = 0.016, respectively). Significant
      difference in intraoperative nitrite concentration was also observed between the
      groups (P = 0.012). Finally, erythrocytes showed a certain endothelial NOS
      activity, which did not differ between the groups, and no differences in the
      inflammatory response were pointed out. The significant reduction of NO(2)(-)
      concentration under continuous perfusion revealed the strong connection among
      perfusion modality, endothelial NO release, and plasmatic nitrite concentration.
      The similar erythrocyte eNOS activity between the groups revealed that the
      differences in blood NO metabolites are mainly ascribable to the endothelium
      release.

PMID- 19860793
TI  - Hemorrhagic stroke in a child with low total serum cholesterol and a pulsatile
      left ventricular assist device.
AB  - Low serum cholesterol has long been associated with hemorrhagic stroke even
      though the mechanism for this association has yet to be elucidated. The
      association of low serum cholesterol with hemorrhagic stroke has been described
      thus far only in adult studies. There have been no reports of this association in
      children. We present a case of a hemorrhagic stroke that occurred in a 6-year
      old, severely malnourished child who had just received augmentation of cardiac
      output with a pulsatile left ventricular assist device.

PMID- 19860794
TI  - Age-related gray matter shrinkage in a treatment naive actively drinking alcohol
      dependent sample.
AB  - BACKGROUND: We previously demonstrated, in a small sample, steeper age-related
      gray matter shrinkage in treatment naive alcohol-dependent (TxN) men compared to
      nonalcoholic controls, but could not separate out the contributions of age and
      lifetime duration of alcohol use (which were highly correlated) to this effect.
      In the current study, we have quadrupled the sample size and expanded it to
      include both men and women to try to replicate and extend the previous findings
      and to separate the contributions of age and alcohol use to the phenomenon.
      METHODS: In the current study, we examine cortical gray matter volumes in 18- to
      50-year-old TxN (n = 84) versus age and gender comparable controls (n = 67). We
      used a new Region of Interest Analysis method which accounts for differences in
      sulcal and gyral enfolding between individuals (Fein et al., 2009a). RESULTS: We
      found greater age-related gray matter shrinkage in TxN than in controls. Partial
      correlation analysis showed that the effect was a function of age and not
      lifetime alcohol burden. CONCLUSIONS: Implications of the findings are discussed
      in terms of their contribution toward our knowledge of differences between
      different subpopulations of alcoholics and in terms of their implications for the
      morbidity of alcohol dependence in an aging national population.

PMID- 19860795
TI  - Heavy episodic drinking and alcohol consumption in French colleges: the role of
      perceived social norms.
AB  - BACKGROUND: The effect of normative perceptions (social norms) on heavy episodic
      drinking (HED) behavior is well known in the U.S. college setting, but little
      work is available in other cultural contexts. The objective of this study is
      therefore to assess whether social norms of alcohol use are related to HED in
      France, taking account of other influential predictors. METHODS: A cross
      sectional survey was carried out among 731 second-year university students in the
      Paris region to explore the role of 29 potential alcohol use risk factors. The
      probability of heavy episodic drinking and the frequency of HED among heavy
      episodic drinkers were modeled independently. Monthly alcohol consumption was
      also assessed. RESULTS: Of the students, 56% overestimate peer student prevalence
      of HED (37% for alcohol drinking prevalence). HED frequency rises with perceived
      peer student prevalence of HED. Other social norms associated with HED are
      perceived friends' approval of HED (increasing both HED probability and HED
      frequency) and perceived friend prevalence of alcohol drinking (increasing HED
      probability only). Cannabis and tobacco use, academic discipline, gender, and the
      number of friends are also identified as being associated with HED. CONCLUSIONS:
      Overestimation of peer student prevalence is not uncommon among French university
      students. Furthermore, perceived peer student prevalence of HED is linked to HED
      frequency, even after adjusting for other correlates. Interventions correcting
      misperceived prevalences of HED among peer students have therefore the potential
      to reduce the frequency of HED in this population.

PMID- 19860797
TI  - Systemic administration of arecoline reduces ethanol-induced sleeping through
      activation of central muscarinic receptor in mice.
AB  - BACKGROUND: Epidemiological evidence of co-use of alcohol and areca nuts suggests
      a potential central interaction between arecoline, a major alkaloid of areca and
      a muscarinic receptor agonist, and ethanol. Moreover, the central cholinergic
      system plays an important role in the depressant action of ethanol and
      barbiturates. The purpose of this study was to investigate the effects of
      arecoline on pentobarbital- and ethanol-induced hypnosis in mice. METHODS: Male
      ICR mice were tested for locomotor activity following acute systemic
      administration of ethanol alone, arecoline alone, or ethanol plus arecoline. For
      the loss of the righting reflex (LORR) induced by pentobarbital and ethanol,
      sleep latency and sleeping duration were evaluated in mice treated with arecoline
      alone or the combination of arecoline and scopolamine or methscopolamine.
      RESULTS: Ethanol (1.0 to 3.0 g/kg, i.p.) reduced locomotor activity significantly
      and a declining trend was observed after treatment with arecoline (0.25 to 1.0
      mg/kg, i.p.), but there were no synergistic effects of ethanol and arecoline on
      locomotor activity. The experiments on LORR demonstrated that arecoline (0.125 to
      1.0 mg/kg, s.c.) shortened the duration of sleeping induced by ethanol (4.0 g/kg,
      i.p.), but not pentobarbital (45 mg/kg, i.p.). In addition, alterations of sleep
      latency were not obvious in both pentobarbital- and ethanol-induced LORR.
      Statistical analyses revealed that scopolamine (centrally acting), but not
      methscopolamine (peripherally acting), could antagonize the effect of arecoline
      on the duration of ethanol-induced LORR in mice. CONCLUSIONS: These results
      suggest that central muscarinic receptor is a pharmacological target for the
      action of arecoline to modulate ethanol-induced hypnosis.

PMID- 19860796
TI  - Linkage analysis of alcohol dependence symptoms in the community.
AB  - BACKGROUND: We have previously identified suggestive linkage for alcohol
      consumption in a community-based sample of Australian adults. In this companion
      paper, we explore the strength of genetic linkage signals for alcohol dependence
      symptoms. METHODS: An alcohol dependence symptom score, based on DSM-IIIR and DSM
      IV criteria, was examined. Twins and their nontwin siblings (1,654 males, 2,518
      females), aged 21 to 81 years, were interviewed, with 803 individuals interviewed
      on 2 occasions, approximately 10 years apart. Linkage analyses were conducted on
      datasets compiled to maximize data collected at either the younger or the older
      age. In addition, linkage was compared between full samples and truncated samples
      that excluded the lightest drinkers (approximately 10% of the sample). RESULTS:
      Suggestive peaks on chromosome 5p (LODs >2.2) were found in a region previously
      identified in alcohol linkage studies using clinical populations. Linkage signal
      strength was found to vary between full and truncated samples and when samples
      differed only on the collection age for a sample subset. CONCLUSIONS: The results
      support the finding that large community samples can be informative in the study
      of alcohol-related traits.

PMID- 19860798
TI  - Polymorphisms of alcohol metabolizing enzymes in indigenous Mexican population:
      unusual high frequency of CYP2E1*c2 allele.
AB  - BACKGROUND: Alcohol abuse represents the major identified etiological factor of
      cirrhosis in Mexico. ADH1B, ALDH2, and CYP2E1 have been considered candidate
      genes in alcohol-related diseases. Controversial results probably due to ethnic
      differences, among other factors, have been reported. Mexican Mestizos (MES)
      derive from the combination of indigenous, Spaniard, and African genes. Huichols
      (HUI) constitute an indigenous group from western Mexico with no racial
      admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in
      healthy HUI and MES from western Mexico. Lipid and hepatic profile were also
      carried out. METHODS: One hundred and one HUI and 331 MES subjects were studied.
      Genotype and allele frequency were assessed through polymerase chain reaction
      restriction fragment length polymorphism after DNA isolation from peripheral
      leukocytes. Commercial kits for lipid and hepatic determinations were used.
      RESULTS: Polymorphic allele distribution in HUI was: 0%ADH1B*2, 0.5%ALDH2*2,
      51.5%CYP2E1*c2; in MES: 3.4%ADH1B*2, 0%ALDH2*2, 16.1%CYP2E1*c2. Frequency of
      ADH1B*2 was statistically (p < 0.001) lower in HUI than MES. CYP2E1*c2
      polymorphic allele was significantly higher (p < 0.0001) in HUI than MES. Hepatic
      profile was normal in both groups. HUI showed a better lipid profile than MES
      independently of genotype. CONCLUSIONS: Huichols exhibited the highest CYP2E1*c2
      allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and
      ALDH2*2 were practically absent. This feature could be useful in the
      understanding of Mexican population gene composition, alcohol metabolism, and
      alcoholic liver disease development. However, further association studies are
      necessary. The heterogeneity of Mexican population was evidenced by the
      significantly different distribution of CYP2E1*c2 allele observed among different
      regions of the country. Lipid and hepatic values were not associated to genotype.
      This report constitutes the first study dealing with gene polymorphisms of
      alcohol metabolizing enzymes conducted in HUI.

PMID- 19860799
TI  - CB1 receptor blockade decreases ethanol intake and associated neurochemical
      changes in fawn-hooded rats.
AB  - BACKGROUND: This study was undertaken to identify the neurochemical changes
      underlying the attenuation of voluntary ethanol intake induced by the cannabinoid
      CB1 receptor antagonist AM251 in fawn-hooded rats. METHODS: Rats were exposed to
      the 2-bottle-choice paradigm (ethanol 10% v/v or water) for 15 days. After this
      period, rats received AM251 (3 to 6 mg/kg, i.p.) or vehicle. RESULTS: Voluntary
      ethanol intake decreased (30%) with the administration of incremental dosages of
      AM251 (3 mg/kg, 5 days and 6 mg/kg, 5 days) in rats with acquired high preferring
      ethanol consumption (>3.5 g of ethanol/kg/d). Ethanol intake significantly
      decreased proopiomelanocortin expression in the arcuate nucleus (38.31%) and
      micro-opioid-DAMGO-stimulated [(35)S]-GTPgamma binding in the caudate-putamen
      (40%), nucleus accumbens core (AccC) (32.87%), and shell (AccS) (34.21%).
      Moreover, ethanol intake increased tyrosine hydroxylase (TH) gene expression in
      the substantia nigra (24%) and ventral tegmental area (23%) and corticotrophin
      releasing gene expression in the paraventricular hypothalamic nucleus (41.6%).
      The reduction of ethanol intake induced by AM251 was associated with blockade or
      significant reduction of the changes produced by ethanol in the expression of
      these genes in key regions related to drug dependence. Interestingly, treatment
      with AM251 reduced (20%) TH gene expression in rats drinking only water. In this
      respect, the action of AM251 in reducing TH gene expression may not be specific.
      CONCLUSION: Taken together, these results revealed that blockade of cannabinoid
      CB1 receptors (CB1r) decreased voluntary ethanol intake in ethanol-habituated
      rats by normalizing the neurochemical alterations induced by ethanol.

PMID- 19860800
TI  - Initial evidence of an association between OPRM1 and adolescent alcohol misuse.
AB  - BACKGROUND: Considerable research efforts have attempted to identify genes
      associated with alcoholism among adults, yet few studies have examined
      adolescents. Identifying genes associated with alcohol misuse in youth is
      important given that the relative contribution of genetic and environmental
      influences on alcoholism varies across development. The purpose of this study was
      to examine the association between a polymorphism of the mu-opioid receptor gene
      (OPRM1) and alcohol misuse in a sample of youth and to test whether heightened
      sensitivity to the reinforcing effects of alcohol mediated this relationship.
      METHODS: Adolescents (n = 187; mean age = 15.4 years; 47.6% female) were
      genotyped for A118G (rs1799971), a single-nucleotide polymorphism (SNP) of the
      OPRM1 gene, and assessed for alcohol use disorder (AUD) diagnoses and other
      psychopathology. Alcohol misuse was also measured continuously to maximize
      detection of drinking problems in youth. Drinking motives were used to capture
      the extent to which youth consumed alcohol to enhance positive affect. RESULTS:
      AUD groups differed significantly in terms of allelic distributions of the A118G
      SNP, such that 51.9% of youth with an AUD carried at least one copy of the G
      allele compared to 16.3% of non-AUD controls. Those who carried the G allele
      endorsed drinking to enhance positive affect more strongly than those who were
      homozygous for the A allele and drinking to enhance positive affect mediated the
      association between OPRM1 and alcohol-related problems. CONCLUSIONS: These data
      build on findings from adult studies and provide the first evidence that a
      polymorphism of the OPRM1 receptor gene is associated with the development of
      early-onset alcohol-related problems during adolescence, in part, by heightening
      sensitivity to the reinforcing effects of alcohol.

PMID- 19860801
TI  - Maternal alcohol use during pregnancy causes systemic oxidation of the
      glutathione redox system.
AB  - BACKGROUND: Increased systemic oxidant stress contributes to a variety of
      maternal complications of pregnancy. Although the antioxidant glutathione (GSH)
      and its oxidized component glutathione disulfide (GSSG) have been demonstrated to
      be significantly altered in the adult alcoholic, the effects of maternal alcohol
      use during pregnancy on oxidant stress in the postpartum female remain under
      investigation. We hypothesized that maternal alcohol use would increase systemic
      oxidant stress in the pregnant female, evidenced by an oxidized systemic GSH
      redox potential. METHODS: As a subset analysis of a larger maternal language
      study, we evaluated the effects of alcohol consumption during pregnancy on the
      systemic GSH redox status of the postpartum female. Using an extensive maternal
      questionnaire, postpartum women where queried regarding their alcohol consumption
      during pregnancy. Any drinking, the occurrence of drinking >3 drinks/occasion,
      and heavy drinking of >5 drinks/occasion during pregnancy were noted. Using HPLC,
      maternal plasma samples were analyzed for GSH, oxidized GSSG and the redox
      potential of the GSH/GSSG antioxidant pair calculated. RESULTS: Maternal alcohol
      use occurred in 25% (83/321) of our study sample. Two in ten women reported
      consuming >3 drinks/occasion during pregnancy, while 1 in 10 women reported
      consuming alcohol at >5 drinks/occasion. Any alcohol use during pregnancy
      significantly decreased plasma GSH (p < 0.05), while alcohol at >3
      drinks/occasion or >5 drinks/occasion significantly decreased plasma GSH
      concentration (p < 0.05), increased the percent of oxidized GSSG (p < 0.05), and
      substantially oxidized the plasma GSH redox potential (p < 0.05). CONCLUSIONS:
      Alcohol use during pregnancy, particularly at levels >3 drinks/occasion, caused
      significant oxidation of the systemic GSH system in the postpartum women. The
      clinical ramifications of the observed alcohol-induced oxidation of the GSH redox
      system on high risk pregnancies or on the exposed offspring require more accurate
      identification and further investigation.

PMID- 19860802
TI  - Neuropeptide S receptor gene expression in alcohol withdrawal and protracted
      abstinence in postdependent rats.
AB  - BACKGROUND: Alcoholism is a chronic disease characterized by frequent
      intoxications followed by withdrawal episodes and relapse to alcohol use.
      Neuroplastic changes associated with these intoxication and withdrawal cycles are
      thought to play a key role in disease progression. Recently, it has been shown
      that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system,
      facilitates relapse to alcohol seeking in laboratory animals. Given that a
      history of ethanol intoxication may increase vulnerability to alcohol addiction,
      we sought to determine whether NPS receptor (NPSR) gene expression is altered
      during withdrawal. METHODS: Rats were subjected to 1 week of intoxication by oral
      alcohol administration. NPSR gene expression was analyzed by in situ
      hybridization in rats 12 hours and 7 days after the last alcohol administration.
      To investigate the functional significance of NPSR system adaptation following
      protracted withdrawal 7 days after intoxication, we tested the anxiolytic-like
      properties of NPS in nondependent and postdependent rats using the shock probe
      defensive burying test (DB). RESULTS: At both time points, increased NPSR gene
      expression was observed in several brain areas, including the endopiriform
      nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases
      in gene expression were also found in the lateral hypothalamus, paraventricular
      nucleus, basolateral and central amygdala. Differences from control animals were
      more pronounced after 7 days of abstinence. The upregulation of the NPSR system
      at this time point was confirmed by functional data indicating that
      intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat)
      elicits more pronounced anxiolytic effects in postdependent animals than in
      controls subjected to the electric shock probe DB test. CONCLUSIONS: Neuropeptide
      S receptor mRNA expression is increased in different brain areas of postdependent
      rats; as shown in the DB test, this expression change is functionally relevant.

PMID- 19860805
TI  - Students' drinker prototypes and alcohol use in a naturalistic setting.
AB  - BACKGROUND: Perceptions about the type of people who drink, also referred to as
      drinker prototypes, may strengthen young people's motivation to engage in alcohol
      use. Previous research has shown that drinker prototypes are related to alcohol
      consumption in both adolescents and young adults. However, the evidence for the
      strength of these relationships remains inconclusive. One of the caveats in
      former studies is that all insights about prototype relations are based on self
      reported data from youngsters themselves, mostly gathered in a class situation,
      which may contain bias due to memory distortions and self-presentation concerns.
      METHODS: The present study examined the impact of drinker prototypes on young
      adults' drinking patterns by using a less obtrusive measure to assess alcohol
      consumption, i.e. ad lib drinking among friend groups in the naturalistic setting
      of a bar lab. Drinker prototypes, self-reported alcohol use in the past, and
      observed alcohol intake in the bar lab were assessed among 200 college students.
      Relations between participants' drinker prototypes and their self-reported and
      observed drinking behavior were examined by computing correlations and conducting
      multilevel analyses. RESULTS: Drinker prototypes were related to both self
      reported and observed alcohol use. However, the drinking patterns of friend group
      members had a strong impact on participants' individual drinking rates in the bar
      lab. After these group effects had been controlled for, only heavy drinker
      prototypes showed relations with observed alcohol intake in the bar lab.
      CONCLUSIONS: These findings further establish the value of drinker prototypes in
      predicting young adults' drinking behavior and suggest that people's motivation
      to drink alcohol in real-life drinking situations is related to their perceptions
      about heavy drinkers.

PMID- 19860803
TI  - Alcohol, cocaine, and brain stimulation-reward in C57Bl6/J and DBA2/J mice.
AB  - BACKGROUND: Pleasure and reward are critical features of alcohol drinking that
      are difficult to measure in animal studies. Intracranial self-stimulation (ICSS)
      is a behavioral method for studying the effects of drugs directly on the neural
      circuitry that underlies brain reward. These experiments had 2 objectives: first,
      to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and
      DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the
      psychostimulant cocaine. METHODS: Male C57 and DBA mice were implanted with
      unipolar stimulating electrodes in the lateral hypothalamus and conditioned to
      spin a wheel for reinforcement by the delivery of rewarding electrical
      stimulation (i.e., brain stimulation-reward or BSR). Using the curve-shift
      method, the BSR threshold (theta(0)) was determined immediately before and after
      oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol
      concentration (BAC) was measured to determine the influence of alcohol metabolism
      on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0,
      30.0 mg/kg) or saline intraperitoneally. RESULTS: In C57 mice, the 0.6 g/kg dose
      of alcohol lowered BSR thresholds by about 20%, during the rising (up to 40
      mg/dl), but not falling, phase of BAC. When given to the DBA mice, alcohol
      lowered BSR thresholds over the entire dose range; the largest reduction was by
      about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was
      more potent in DBA mice than in C57 mice as revealed by a leftward shift in the
      cocaine dose-response curve. For both alcohol and cocaine, effects on BSR
      threshold were dissociable from effects on operant response rates. CONCLUSIONS:
      In C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol
      to potentiate the neural mechanisms of brain reward. The DBA mice are more
      sensitive to the reward-potentiating effects of both alcohol and cocaine,
      suggesting that there are mouse strain differences in the neural mechanisms of
      brain reward that can be measured with the ICSS technique.

PMID- 19860804
TI  - Galanin knockout mice show disturbances in ethanol consumption and expression of
      hypothalamic peptides that stimulate ethanol intake.
AB  - BACKGROUND: There is growing evidence suggesting that hypothalamic galanin (GAL),
      which is known to stimulate intake of a fat-rich diet, has a role in promoting
      the consumption of ethanol. The present study further examined this possibility
      in GAL knockout (GALKO) mice. METHODS: Two groups of female and male GALKO mice,
      compared to wild-type (WT) controls, were trained to voluntarily drink increasing
      concentrations of ethanol, while maintained on lab chow and water. They were
      examined in terms of their daily ethanol intake and preference, acute consumption
      of a high-fat diet, preference for flavored solutions, and expression of
      different peptides shown to stimulate ethanol intake. RESULTS: In the GALKO mice
      compared to WT, the results revealed: (i) a 35 to 45% decrease in ethanol intake
      and preference, which was evident only at the highest (15%) ethanol
      concentration, was stronger in female than in male mice, and was seen with
      comparisons to littermate as well as nonlittermate WT mice; (ii) a 48% decrease
      in acute intake of a fat-rich diet, again stronger in female than male mice;
      (iii) no difference in consumption of sucrose or quinine solutions in preference
      tests; (iv) a total loss of GAL mRNA in the hypothalamic paraventricular nucleus
      (PVN) of female and male mice; and (v) a gender-specific change in mRNA levels of
      peptides in the perifornical lateral hypothalamus (PFLH), orexin and melanin
      concentrating hormone, which are known to stimulate ethanol and food intake and
      were markedly decreased in females while increased in males. CONCLUSIONS: These
      results provide strong support for a physiological role of PVN GAL in stimulating
      the consumption of ethanol, as well as a fat-rich diet. Ablation of the GAL gene
      produced a behavioral phenotype, particularly in females, which may reflect the
      functional relationship of galanin to ovarian steroids. It also altered the
      peptides in the PFLH, with their reduced expression contributing to the larger
      behavioral effects observed in females and their increased expression attenuating
      these effects in males.

PMID- 19860806
TI  - Ethanol upregulates iNOS expression in colon through activation of nuclear factor
      kappa B in rats.
AB  - BACKGROUND: Alcohol inhibits colonic motility but the mechanism is unknown. The
      goal of this study was to test the possibility that nuclear factor-kappa B (NF
      kappaB) is involved in the upregulation of inducible nitric oxide synthase (iNOS)
      expression induced by ethanol in colon. METHODS: The isometric contraction of
      longitudinal muscle strips of proximal colon (LP) was monitored by polygraph.
      Western blot analysis was used to measure the amount of iNOS and I-kappaB in the
      cytoplasm and P65 in the nucleus. Immunohistochemistry was applied to locate iNOS
      in colon. RESULTS: Ethanol (87mM) inhibited the contraction of LP. Pretreatment
      of S-methylisothioure (SMT) (1 mM), a specific iNOS inhibitor, Pyrrolidine
      dithiocarbamate (PDTC) (10 mM) and BAY11-7082(10 mM), specific inhibitors of NF
      kappaB significantly reversed the inhibitory effect of ethanol on LP contraction.
      Ethanol increased the amount of iNOS and content of NO in colon, and these
      effects were attenuated by pretreatment of PDTC. Following ethanol
      administration, the amount of I-kappaB in the cytoplasm decreased, but that of
      P65, the subunit of NF-kappaB in the nucleus, increased. The iNOS was located in
      the cell body of myenteric plexus in colon. CONCLUSION: Ethanol inhibited the
      contraction of LP in colon mainly through activation of NF-kappaB, the subsequent
      upregulation of iNOS expression and increase of NO release in myenteric plexus.

PMID- 19860808
TI  - Increased acid sphingomyelinase activity in peripheral blood cells of acutely
      intoxicated patients with alcohol dependence.
AB  - BACKGROUND: Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane
      sphingomyelin into the bioactive lipid ceramide and is thus involved in different
      cellular processes such as differentiation, immunity, or cell death. Activation
      of ASM has been reported in particular in conjunction with the cellular stress
      response to several external stimuli, and increased ASM activity was observed in
      a variety of human diseases. Ethanol-induced activation of ASM has been observed
      in different cell culture systems, thus raising the question about the effect of
      alcohol intoxication in human subjects on ASM activity in vivo. METHODS: We
      determined ASM activity in peripheral blood mononucleated cells of 27 patients
      suffering from alcohol dependence. Patients were classified according to their
      blood alcohol concentration at admission, and ASM activity was determined
      repeatedly from all patients during alcohol withdrawal. RESULTS: Acutely
      intoxicated patients displayed significantly higher ASM activity than patients in
      early abstinence (Mann-Whitney U test: Z = - 2.6, p = 0.009). ASM activity
      declined in acutely intoxicated patients to normal values with the transition
      from the intoxicated state to early abstinence (Wilcoxon test: Z = -2.7, p =
      0.007). At the end of withdrawal, ASM activity was significantly increased again
      compared to the early phase of abstinence in both patient groups (Wilcoxon test:
      Z = -2.691, p = 0.007 and Z = -2.275, p = 0.023, respectively). CONCLUSIONS:
      Alcohol-induced activation of ASM occurs in human subjects and might be
      responsible for deleterious effects of ethanol intoxication. Chronic alcohol
      abuse may induce deregulation of sphingomyelin metabolism in general, and this
      impairment may cause side effects during withdrawal from alcohol.

PMID- 19860807
TI  - Alcohol up-regulates TLR2 through a NO/cGMP dependent pathway.
AB  - BACKGROUND: Heavy alcohol consumption is associated with severe bronchitis. This
      is likely related to increased inflammation in the airways of alcohol abusers.
      Toll-like receptor 2 (TLR2) is an important mediator of inflammation in the
      airway epithelium. TLR2 initiates an inflammatory cascade in response to gram
      positive bacteria. We have previously shown that alcohol up-regulates TLR2 in the
      airway epithelium. However, the mechanism of alcohol-mediated up-regulation of
      TLR2 has not been identified. METHODS: A human airway epithelial cell line,
      16HBE14o-, was exposed to biologically relevant concentrations of alcohol (100
      mM) in the presence and absence of N(omega)-Nitro-l-arginine methyl ester
      hydrochloride, a nitric oxide (NO) synthase inhibitor; and Rp-8-Br-cGMP-S, an
      antagonist analogue of cGMP. TLR2 was measured using real-time PCR and Western
      blots. In addition, 16HBE14o- cells were incubated with sodium nitroprusside
      (SNP), an NO donor, and 8-Br-cGMP, a cGMP analogue. TLR2 was measured using real
      time PCR. RESULTS: N(omega)-Nitro-l-arginine methyl ester hydrochloride blocked
      the alcohol-mediated up-regulation of TLR2. This indicates that NO plays a key
      role in alcohol's up-regulation of TLR2. SNP, a NO donor, up-regulated TLR2. Rp-8
      Br-CGMP-S attenuated alcohol's up-regulation of TLR2, suggesting that NO was
      working through cGMP/PKG. 8-Br-cGMP up-regulated TLR2, also demonstrating the
      importance of cGMP/PKG. CONCLUSIONS: Alcohol up-regulates TLR2 through a
      NO/cGMP/PKG dependent pathway in the airway epithelium. This is an important
      observation in the understanding how alcohol modulates airway inflammation. In
      addition, this is the first time that cyclic nucleotides have been shown to play
      a role in the regulation of TLR2.

PMID- 19860809
TI  - Glycine receptors in the nucleus accumbens involved in the ethanol intake
      reducing effect of acamprosate.
AB  - BACKGROUND: We have previously demonstrated that strychnine-sensitive glycine
      receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine
      receptors (nAChRs) in the ventral tegmental area are involved in mediating
      ethanol (EtOH)-induced elevation of dopamine in the rat mesolimbic dopamine
      system. This neuronal circuitry was also demonstrated to mediate dopamine
      elevation in the nAc after both taurine, an endogenous agonist of GlyRs, and
      acamprosate, a synthetic derivate of homotaurine. The aim of this study was to
      investigate whether the EtOH intake-reducing effect of acamprosate involves
      accumbal GlyRs. METHODS: For this purpose, we used a voluntary EtOH consumption
      model where EtOH medium- and high-preferring rats were implanted with guide
      cannulae in the nAc. The animals received daily injections of acamprosate or 0.9%
      NaCl before accessing a bottle of 6% EtOH and a bottle of water. After 2 days, a
      microinjection of strychnine or vehicle preceded the daily systemic injection and
      bottle-access period. RESULTS: Acamprosate, but not saline, decreased EtOH
      intake. Pretreatment with Ringer in the nAc did not influence EtOH intake in
      saline or acamprosate-treated animals. Pretreatment with strychnine had no effect
      on EtOH intake in saline-treated animals, whereas it completely reversed the EtOH
      intake-reducing effect of acamprosate. CONCLUSIONS: Based on current and previous
      results, we suggest that acamprosate primarily interacts with accumbal GlyRs and
      secondarily with ventral tegmental nAChRs, in a similar manner to that previously
      observed with EtOH and taurine. The interaction between acamprosate and GlyRs
      does not only influence dopamine output in the nAc but also EtOH consumption,
      giving further support for our hypothesis that GlyRs are of importance in EtOH
      reinforcement.

PMID- 19860810
TI  - Glycine receptors involved in acamprosate's modulation of accumbal dopamine
      levels: an in vivo microdialysis study.
AB  - BACKGROUND: Glycine receptors (GlyRs) in the nucleus accumbens (nAc) and
      nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA)
      have been suggested to be involved in the positive reinforcing and dopamine
      elevating effects of ethanol. Recent studies have also shown that ethanol high
      preferring rats substantially decrease their ethanol intake when treated with a
      glycine transporter 1 inhibitor (ORG 25935). Acamprosate, a drug used for relapse
      prevention in treatment of alcohol dependence, has also been demonstrated to
      elevate extracellular dopamine levels in the nAc. However, the underlying
      mechanism of action of acamprosate is not fully understood. Here we investigated
      whether acamprosate interferes with a neuronal circuitry that previously has been
      demonstrated to be involved in the dopamine elevating effects of ethanol and
      taurine. METHODS: In vivo microdialysis in freely moving rats was used to assess
      accumbal dopamine levels before and during local (nAc) or systemic administration
      of acamprosate. RESULTS: Perfusion of 0.5 mM acamprosate in the nAc significantly
      increased dopamine levels. Pretreatment either with 10 microM strychnine in the
      nAc or 100 microM mecamylamine in the VTA, completely antagonized the acamprosate
      induced elevation of accumbal dopamine levels. Also, systemic acamprosate
      administration elevated accumbal dopamine output, an effect that was abolished by
      local (nAc) pretreatment with 10 microM strychnine. CONCLUSIONS: These results
      suggest that both systemic and local application of acamprosate elevate
      extracellular dopamine levels in the nAc by activating accumbal GlyRs, and,
      secondarily, tegmental nAChRs.

PMID- 19860812
TI  - Alcohol, signaling, and ECM turnover.
AB  - Alcohol is recognized as a direct hepatotoxin, but the precise molecular pathways
      that are important for the initiation and progression of alcohol-induced tissue
      injury are not completely understood. The current understanding of alcohol
      toxicity to organs suggests that alcohol initiates injury by generation of
      oxidative and nonoxidative ethanol metabolites and via translocation of gut
      derived endotoxin. These processes lead to cellular injury and stimulation of the
      inflammatory responses mediated through a variety of molecules. With continuing
      alcohol abuse, the injury progresses through impairment of tissue regeneration
      and extracellular matrix (ECM) turnover, leading to fibrogenesis and cirrhosis.
      Several cell types are involved in this process, the predominant being stellate
      cells, macrophages, and parenchymal cells. In response to alcohol, growth factors
      and cytokines activate many signaling cascades that regulate fibrogenesis. This
      mini-review brings together research focusing on the underlying mechanisms of
      alcohol-mediated injury in a number of organs. It highlights the various
      processes and molecules that are likely involved in inflammation, immune
      modulation, susceptibility to infection, ECM turnover and fibrogenesis in the
      liver, pancreas, and lung triggered by alcohol abuse.

PMID- 19860811
TI  - Alcohol stimulates activation of Snail, epidermal growth factor receptor
      signaling, and biomarkers of epithelial-mesenchymal transition in colon and
      breast cancer cells.
AB  - BACKGROUND: Alcohol consumption is associated with the risk of progressive
      cancers including colon and breast cancer. The mechanisms for the alcohol-induced
      aggressive behavior of these epithelial cancer cells have not been fully
      identified. Epithelial-mesenchymal transition (EMT) is a developmental program
      recently shown to play a role in cancer progression and metastases. We
      hypothesized that alcohol might promote cancer progression by inducing EMT in
      cancer cells and tested this hypothesis by assessing alcohol-stimulated changes
      in phenotypic markers of EMT as well as the EMT transcription factor Snail and
      its related cell signaling. METHODS: Colon and breast cancer cell lines and a
      normal intestinal epithelial cell line were tested as well as colonic mucosal
      biopsy samples from alcoholic subjects. Cells were treated with alcohol and
      assessed for EMT-related changes using immunofluorescent microscopy, western
      blotting, reporter assays, RT-PCR, and knockdown of Snail with siRNA. RESULTS: We
      show alcohol upregulated the signature EMT phenotypic marker vimentin as well as
      matrix metalloprotease (MMP)-2, MMP-7, and MMP-9 and cell migration in colon and
      breast cancer cells-all characteristics of EMT. Alcohol also stimulated nuclear
      localization of Snail phosphorylated at Ser246, transcription from a Snail
      reporter plasmid, and Snail mRNA expression by RT-PCR. Snail siRNA knockdown
      prevented alcohol-stimulated vimentin expression. In vivo, Snail expression was
      significantly elevated in colonic mucosal biopsies from alcoholics. Also, we
      found alcohol stimulated activation of epidermal growth factor receptor (EGFR)
      signaling and an EGFR inhibitor blocked alcohol-induced cell migration and Snail
      mRNA expression. CONCLUSIONS: Collectively, our data support a novel mechanism
      for alcohol promoting cancer progression through stimulating the EMT program in
      cancer cells via an EGFR-Snail mediated pathway. This study reveals new pathways
      for alcohol-mediated promotion of cancer that could be targeted for therapy or
      prevention of alcohol-related cancers.

PMID- 19860815
TI  - Roles of plasma exudation in asthma and COPD.

PMID- 19860813
TI  - Magnetic resonance microscopy defines ethanol-induced brain abnormalities in
      prenatal mice: effects of acute insult on gestational day 7.
AB  - BACKGROUND: This magnetic resonance microscopy (MRM)-based report is the second
      in a series designed to illustrate the spectrum of craniofacial and central
      nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal
      ethanol treatment. The study described in this report examined the consequences
      of ethanol exposure on gestational day (GD) 7 in mice, a time in development when
      gastrulation and neural plate development begins; corresponding to the mid- to
      late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice
      has previously been shown to result in CNS defects consistent with
      holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal
      Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD
      7 ethanol-induced defects. METHODS: C57Bl/6J female mice were intraperitoneally
      (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of
      pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for
      imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at
      either 7.0 Tesla (T) or 9.4 T. Resulting 29 microm isotropic spatial resolution
      scans were segmented and reconstructed to provide 3D images. Linear and
      volumetric brain measures, as well as morphological features, were compared for
      control and ethanol-exposed fetuses. Following MRM, selected specimens were
      processed for routine histology and light microscopic examination. RESULTS:
      Gestational day 7 ethanol exposure resulted in a spectrum of median facial and
      forebrain deficiencies, as expected. This range of abnormalities falls within the
      HPE spectrum; a spectrum for which facial dysmorphology is consistent with and
      typically is predictive of that of the forebrain. In addition, other defects
      including median facial cleft, cleft palate, micrognathia, pituitary agenesis,
      and third ventricular dilatation were identified. MRM analyses also revealed
      cerebral cortical dysplasia/heterotopias resulting from this acute, early insult
      and facilitated a subsequent focused histological investigation of these defects.
      CONCLUSIONS: Individual MRM scans and 3D reconstructions of fetal mouse brains
      have facilitated demonstration of a broad range of GD 7 ethanol-induced
      morphological abnormality. These results, including the discovery of cerebral
      cortical heterotopias, elucidate the teratogenic potential of ethanol insult
      during the third week of human prenatal development.

PMID- 19860816
TI  - Basophil activation test in the diagnosis of insect venom allergies.

PMID- 19860817
TI  - Increased vascular permeability precedes cellular inflammation as asthma control
      deteriorates.
AB  - BACKGROUND: Airway microcirculation is abnormal in asthma but the role of
      vascular changes in asthma deteriorations remains poorly defined. We
      prospectively assessed the vascular changes accompanying worsening of asthma
      control by using an inhaled corticosteroid (ICS) dose-reduction model.
      OBJECTIVES: To evaluate airway vascularity, vascular permeability and expression
      of vascular endothelial growth factor (VEGF) in early asthma deterioration
      induced by ICS back-titration. METHODS: Twenty mild-to-moderate persistent
      symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4
      weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom
      control. This was followed by dose reduction to half of the pre-study doses for 4
      8 weeks until the symptoms began to return. Endobronchial biopsy and
      bronchoalveolar lavage (BAL) samples were obtained after both treatment periods.
      RESULTS: Vascularity as measured by the number and size of blood vessels, as well
      as VEGF expression did not change following ICS reduction. Even on high-dose ICS,
      perivascular albumin staining and BAL microalbumin levels in asthmatic subjects,
      as markers of permeability, were elevated when compared with normal subjects and
      both further increased significantly after ICS reduction. There was a significant
      association between changes in vascular leakiness and clinical deterioration.
      Increases in airway albumin correlated with previously reported increases in
      airway wall infiltration with T lymphocytes. CONCLUSIONS: Our results suggest
      that airway vascular leakage is a major pathophysiologic feature of early asthma
      deterioration, occurring before recrudescence of cellular inflammation.

PMID- 19860818
TI  - Midostaurin (PKC412) inhibits immunoglobulin E-dependent activation and mediator
      release in human blood basophils and mast cells.
AB  - BACKGROUND: KIT tyrosine kinase inhibitors (TKI), such as nilotinib or
      midostaurin (PKC412), are increasingly used in clinical trials to counteract
      neoplastic cell growth in patients with aggressive mast cell (MC) disorders.
      However, these patients suffer not only from MC infiltration and consecutive
      organ damage but also from MC mediator-related symptoms. METHODS: We examined the
      effects of three KIT TKI, imatinib, nilotinib, and midostaurin, on IgE-dependent
      mediator release in normal human blood basophils and cultured cord blood cell
      derived MC, and on spontaneous histamine secretion in the MC leukaemia cell line
      HMC-1 and the basophil cell line KU812. RESULTS: The multi-kinase inhibitor
      midostaurin that interacts with KIT and protein kinase C was found to counteract
      anti-IgE-induced mediator release in blood basophils and cultured cord blood cell
      derived MC in all samples examined. By contrast, no effects of imatinib or
      nilotinib on histamine secretion in basophils or MC were found. The effects of
      midostaurin on histamine release were dose-dependent and occurred at
      pharmacologic concentrations (IC(50) 10-100 nm). Midostaurin was also found to
      inhibit the IgE-dependent up-regulation of CD63 on cultured cord blood cell
      derived human MC, but did not inhibit IgE-dependent up-regulation of CD63 or
      CD203c in human blood basophils. CONCLUSION: Midostaurin may be a beneficial drug
      in aggressive systemic mastocytosis not only because of its growth-inhibitory
      effects but also because of its additional effects on activation and mediator
      release in MC and basophils.

PMID- 19860820
TI  - Measuring health-related quality of life: fundamental methodological issues.

PMID- 19860819
TI  - The interaction of glutathione S-transferase M1-null variants with tobacco smoke
      exposure and the development of childhood asthma.
AB  - BACKGROUND: The glutathione S-transferase M1 (GSTM1)-null variant is a common
      copy number variant associated with adverse pulmonary outcomes, including asthma
      and airflow obstruction, with evidence of important gene-by-environment
      interactions with exposures to oxidative stress. OBJECTIVE: To explore the joint
      interactive effects of GSTM1 copy number and tobacco smoke exposure on the
      development of asthma and asthma-related phenotypes in a family-based cohort of
      childhood asthmatics. METHODS: We performed quantitative PCR-based genotyping for
      GSTM1 copy number in children of self-reported white ancestry with mild to
      moderate asthma in the Childhood Asthma Management Program. Questionnaire data
      regarding intrauterine (IUS) and post-natal, longitudinal smoke exposure were
      available. We performed both family-based and population-based tests of
      association for the interaction between GSTM1 copy number and tobacco smoke
      exposure with asthma and asthma-related phenotypes. RESULTS: Associations of
      GSTM1-null variants with asthma (P=0.03), younger age of asthma symptom onset
      (P=0.03), and greater airflow obstruction (reduced forced expiratory volume in 1
      s / forced vital capacity, P=0.01) were observed among the 50 children (10% of
      the cohort) with exposure to IUS. In contrast, no associations were observed
      between GSTM1-null variants and asthma-related phenotypes among children without
      IUS exposure. Presence of at least one copy of GSTM1 conferred protection.
      CONCLUSION: These findings support an important gene-by-environment interaction
      between two common factors: increased risk of asthma and asthma-related
      phenotypes conferred by GSTM1-null homozygosity in children is restricted to
      those with a history of IUS exposure.

PMID- 19860823
TI  - Clinical and microbiological characteristics of Nocardiosis including those
      caused by emerging Nocardia species in Taiwan, 1998-2008.
AB  - The genus of Nocardia is rapidly expanding and the species distribution varies
      with different geographical locations. We retrospectively reviewed the laboratory
      records of the bacteriology laboratory at National Taiwan University Hospital
      from January 1998 to June 2008 to identify patients with nocardiosis. During the
      study period, 164 isolates of Nocardia spp. were identified from 134 patients but
      only 113 patients had Nocardia infection. Nocardia brasiliensis (n = 54) was the
      most common pathogen, followed by N. asteroides (n = 36), N. farcinica (n = 7),
      N. flavorosea (n = 4), N. otitidiscaviarum (n = 3), N. nova (n = 3), N.
      beijingensis (n = 2) and one each of N. puris, N. jinanensis and N. takedensis.
      The major types of infection were cutaneous infection (56.6%), pulmonary
      infection (33.6%) and disseminated infection (7.1%). Eighty-eight patients
      received sulfonamide-containing antibiotic and eight of 100 patients with
      available data on outcomes died during the episode of nocardiosis. In conclusion,
      the clinical and microbiological manifestations of Nocardiosis vary with the
      different Nocardia species. Accurate identification of the species is crucial to
      make the diagnosis.

PMID- 19860824
TI  - Modeling of ATP-ADP steady-state exchange rate mediated by the adenine nucleotide
      translocase in isolated mitochondria.
AB  - A computational model for the ATP-ADP steady-state exchange rate mediated by
      adenine nucleotide translocase (ANT) versus mitochondrial membrane potential
      dependence in isolated rat liver mitochondria is presented. The model represents
      the system of three ordinary differential equations, and the basic components
      included are ANT, F(0)/F(1)-ATPase, and the phosphate carrier. The model
      reproduces quantitatively the relationship between mitochondrial membrane
      potential and the ATP-ADP steady-state exchange rate mediated by the ANT
      operating in the forward mode, with the assumption that the phosphate carrier
      functions under rapid equilibrium. Furthermore, the model can simulate the
      kinetics of experimentally measured data on mitochondrial membrane potential
      titrated by an uncoupler. Verified predictions imply that the ADP influx rate is
      highly dependent on the mitochondrial membrane potential, and in the 0-100 mV
      range it is close to zero, owing to extremely low matrix ATP values. In addition
      to providing theoretical values of free matrix ATP and ADP, the model explains
      the diminished ADP-ATP exchange rate in the presence of nigericin, a condition in
      which there is hyperpolarization of the inner mitochondrial membrane at the
      expense of the mitochondrial Delta pH gradient; the latter parameter influences
      matrix inorganic phosphate and ATP concentrations in a manner also described.

PMID- 19860825
TI  - Probing the catalytic potential of the hamster arylamine N-acetyltransferase 2
      catalytic triad by site-directed mutagenesis of the proximal conserved residue,
      Tyr190.
AB  - Arylamine N-acetyltransferases (NATs) play an important role in both the
      detoxification of arylamine and hydrazine drugs and the activation of arylamine
      carcinogens. Because the catalytic triad, Cys-His-Asp, of mammalian NATs has been
      shown to be essential for maintaining protein stability, rendering it impossible
      to assess alterations of the triad on catalysis, we explored the impact of the
      highly conserved proximal residue, Tyr190, which forms a direct hydrogen bond
      interaction with one of the triad residues, Asp122, as well as a potential pi-pi
      stacking interaction with the active site His107. The replacement of hamster NAT2
      Tyr190 by either Phe, Ile or Ala was well tolerated and did not result in
      significant alterations in the overall fold of the protein. Nevertheless, stopped
      flow and steady-state kinetic analysis revealed that Tyr190 was critical for
      maximizing the acetylation rate of NAT2 and the transacetylation rate of p
      aminobenzoic acid when compared with the wild-type. Tyr190 was also shown to play
      an important role in determining the pK(a) of the active site Cys during
      acetylation, as well as the pH versus the rate profile for transacetylation. We
      hypothesized that the pH dependence was associated with global changes in the
      active site structure, which was revealed by the superposition of [(1)H, (15)N]
      heteronuclear single quantum coherence spectra for the wild-type and Y190A. These
      results suggest that NAT2 catalytic efficiency is partially governed by the
      ability of Tyr190 to mediate the collective impact of multiple side chains on the
      electrostatic potential and local conformation of the active site.

PMID- 19860826
TI  - Serum autoantibodies as biomarkers for early cancer detection.
AB  - Autoantibodies against autologous tumor-associated antigens have been detected in
      the asymptomatic stage of cancer and can thus serve as biomarkers for early
      cancer diagnosis. Moreover, because autoantibodies are found in sera, they can be
      screened easily using a noninvasive approach. Consequently, many studies have
      been initiated to identify novel autoantibodies relevant to various cancer types.
      To facilitate autoantibody discovery, approaches that allow the simultaneous
      identification of multiple autoantibodies are preferred. Five such techniques-
      SEREX, phage display, protein microarray, SERPA and MAPPing--are discussed here.
      In the second part of this review, we discussed autoantibodies found in the five
      most common cancers (lung, breast, colorectal, stomach and liver). The discovery
      of panels of tumor-associated antigens and autoantibody signatures with high
      sensitivity and specificity would aid in the development of diagnostics,
      prognostics and therapeutics for cancer patients.

PMID- 19860827
TI  - Antibody-based proteomics: analysis of signaling networks using reverse protein
      arrays.
AB  - Protein kinases drive the cellular signal transduction networks that underlie the
      regulation of growth, survival and differentiation. To repair the deregulations
      of signaling cascades that are associated with numerous disease states,
      therapeutic strategies, based on controlling aberrant protein kinase activity,
      are emerging. To develop such therapies it is crucial to have knowledge of the
      full complexity of signaling networks at a molecular level in order to understand
      the information flow through signaling cascades and their cell and tissue
      specificity. Antibody-based proteomic approaches (such as reverse-phase protein
      microarrays) are a powerful tool for using to obtain those signaling maps,
      through the study of phosphorylation states of pathway components using
      antibodies that specifically recognize the phosphorylated form of kinase
      substrates.

PMID- 19860829
TI  - Alternative splicing produces an H-protein with better substrate properties for
      the P-protein of glycine decarboxylase.
AB  - Several thousand plant genes are known to produce multiple transcripts, but the
      precise function of most of the alternatively encoded proteins is not known.
      Alternative splicing has been reported for the H-protein subunit of glycine
      decarboxylase in the genus Flaveria. H-protein has no catalytic activity itself
      but is a substrate of the three enzymatically active subunits, P-, T- and L
      protein. In C(4) species of Flaveria, two H-proteins originate from single genes
      in an organ-dependent manner. Here, we report on differences between the two
      alternative H-protein variants with respect to their interaction with the glycine
      decarboxylating subunit, P-protein. Steady-state kinetic analyses of the
      alternative Flaveria H-proteins and artificially produced 'alternative'
      Arabidopsis H-proteins, using either pea mitochondrial matrix extracts or
      recombinant cyanobacterial P-protein, consistently demonstrate that the
      alternative insertion of two alanine residues at the N-terminus of the H-protein
      elevates the activity of P-protein by 20%in vitro, and could promote glycine
      decarboxylase activity in vivo.

PMID- 19860828
TI  - Tyrosine-dependent basolateral targeting of human connexin43-eYFP in Madin-Darby
      canine kidney cells can be disrupted by the oculodentodigital dysplasia mutation
      L90V.
AB  - Polarized membrane sorting of connexin 43 (Cx43) has not been well-characterized.
      Based on the presence of a putative sorting signal, YKLV(286-289), within its C
      terminal cytoplasmic domain, we hypothesized that Cx43 is selectively expressed
      on the basolateral surface of Madin-Darby canine kidney (MDCK) cells in a
      tyrosine-dependent manner. We generated stable MDCK cell lines expressing human
      wild-type and mutant Cx43-eYFP, and analyzed the membrane localization of Cx43
      eYFP within polarized monolayers using confocal microscopy and selective surface
      biotinylation. We found that wild-type Cx43-eYFP was selectively targeted to the
      basolateral membrane domain of MDCK cells. Substitution of alanine for Y286
      disrupted basolateral targeting of Cx43-eYFP. Additionally, substitution of a
      sequence containing the transferrin receptor internalization signal, LSYTRF, for
      PGYKLV(284-289) also disrupted basolateral targeting. Taken together, these
      results indicate that Y286 in its native amino acid sequence is necessary for
      targeting Cx43-eYFP to the basolateral membrane domain of MDCK cells. To
      determine whether the F52dup or L90V oculodentodigital dysplasia-associated
      mutations could affect polarized sorting of Cx43-eYFP, we analyzed the expression
      of these Cx43-eYFP mutant constructs and found that the L90V mutation disrupted
      basolateral expression. These findings raise the possibility that some
      oculodentodigitial dysplasia-associated mutations contribute to disease by
      altering polarized targeting of Cx43.

PMID- 19860830
TI  - The interaction between casein kinase Ialpha and 14-3-3 is phosphorylation
      dependent.
AB  - We have previously shown that casein kinase (CK) Ialpha from mammalian brain
      phosphorylates 14-3-3 zeta and tau isoforms on residue 233. In the present study,
      we show that CKIalpha associates with 14-3-3 both in vitro and in vivo. The
      interaction between CKIalpha and 14-3-3 is dependent on CKIalpha phosphorylation,
      unlike centaurin-alpha1 (also known as ADAP1), which binds to unphosphorylated
      CKIalpha on the same region. CKIalpha preferentially interacts with mammalian eta
      and gamma 14-3-3 isoforms, and peptides that bind to the 14-3-3 binding pocket
      prevent this interaction. The region containing Ser218 in this CKIalpha binding
      site was mutated and the interaction between CKIalpha and 14-3-3 was reduced. We
      subsequently identified a second phosphorylation-dependent 14-3-3 binding site
      within CKIalpha containing Ser242 that may be the principal site of interaction.
      We also show that both fission and budding yeast CKI kinase homologues
      phosphorylate mammalian and budding yeast (BMH1 and BMH2) 14-3-3 at the
      equivalent site.

PMID- 19860831
TI  - Fatty aldehyde dehydrogenase is up-regulated by polyunsaturated fatty acid via
      peroxisome proliferator-activated receptor alpha and suppresses polyunsaturated
      fatty acid-induced endoplasmic reticulum stress.
AB  - Fatty aldehyde dehydrogenase (FALDH; also known as ALDH3A2 or ALDH10) oxidizes
      medium- or long-chain aliphatic aldehydes. FALDH deficiency in humans is known to
      be the cause of Sjogren-Larsson syndrome, in which individuals display
      neurological symptoms and cutaneous abnormality. FALDH-V, a splice isoform of
      FALDH, is localized in the peroxisome and contributes to the oxidization of
      pristanal, an intermediate of the alpha-oxidation pathway. FALDH-N, another
      splice isoform of FALDH, is induced by peroxisomal proliferator-activated
      receptor alpha ligands, although its activation mechanism has not been clarified.
      In the present study, we show that transcriptional activation of FALDH is
      directly regulated by peroxisomal proliferator-activated receptor alpha through a
      direct repeat-1 site located in the FALDH promoter. In addition, FALDH is
      efficiently induced by linoleic acid in rat hepatoma Fao cells through
      transcriptional activation by peroxisomal proliferator-activated receptor alpha.
      Furthermore, ectopic expression of endoplasmic reticulum-localizing FALDH-N, but
      not peroxisome-localizing FALDH-V, suppresses endoplasmic reticulum stress caused
      by linoleic acid in HEK293 cells. These results suggest the autocatalytic nature
      of the FALDH-N system against endoplasmic reticulum stress that is induced by
      polyunsaturated fatty acid; polyunsaturated fatty acid binds to peroxisomal
      proliferator-activated receptor alpha to activate the expression of FALDH-N,
      which then detoxifies polyunsaturated fatty acid-derived fatty aldehydes and
      protects cells from endoplasmic reticulum stress.

PMID- 19860832
TI  - The changing patterns of covalent active site occupancy during catalysis on a
      modular polyketide synthase multienzyme revealed by ion-trap mass spectrometry.
AB  - A catalytically competent, homodimeric diketide synthase comprising the first
      extension module of the erythromycin polyketide synthase was analysed using MS,
      after limited proteolysis to release functional domains, to determine the pattern
      of covalent attachment of substrates and intermediates to active sites during
      catalysis. Using the natural substrates, the acyltransferase and acylcarrier
      protein of the loading module were found to be heavily loaded with propionyl
      starter groups, while the ketosynthase was fully propionylated. The acylcarrier
      protein of the extension module was partly occupied by the product diketide, and
      the adjacent chain-releasing thioesterase domain was vacant, implying that the
      rate-limiting step is transfer of the diketide from the acylcarrier protein to
      the thioesterase domain. The data suggest an attractive model for preventing
      iterative chain extension by efficient repriming of the ketosynthase domain after
      condensation. Use of the alternative starter unit valeryl-CoA produced an altered
      pattern, in which a significant proportion of the extension acylcarrier protein
      was loaded with methylmalonate, not diketide, consistent with the condensation
      step having become an additional slow step. Strikingly, when NADPH was omitted,
      the extension acylcarrier protein contained methylmalonate and none of the
      expected keto diketide, in contrast to results obtained previously by mixing
      individual recombinant domains, showing the importance of also studying intact
      modules. The detailed patterns of loading of the extension acylcarrier protein
      (of which there are two in the homodimer) also provided the first evidence for
      simultaneous loading of both acylcarrier proteins and for the coordination of
      timing between the two active centres for chain extension.

PMID- 19860833
TI  - Caenorhabditis elegans metallothionein isoform specificity--metal binding
      abilities and the role of histidine in CeMT1 and CeMT2.
AB  - Two metallothionein (MT) isoforms have been identified in the model nematode
      Caenorhabditis elegans: CeMT1 and CeMT2, comprising two polypeptides that are 75
      and 63 residues in length, respectively. Both isoforms encompass a conserved
      cysteine pattern (19 in CeMT1 and 18 in CeMT2) and, most significantly, as a
      result of their coordinative potential, CeMT1 includes four histidines, whereas
      CeMT2 has only one. In the present study, we present a comprehensive and
      comparative analysis of the metal [Zn(II), Cd(II) and Cu(I)] binding abilities of
      CeMT1 and CeMT2, performed through spectroscopic and spectrometric
      characterization of the recombinant metal-MT complexes synthesized for wild-type
      isoforms (CeMT1 and CeMT2), their separate N- and C-terminal moieties (NtCeMT1,
      CtCeMT1, NtCeMT2 and CtCeMT2) and a DeltaHisCeMT2 mutant. The corresponding in
      vitro Zn/Cd- and Zn/Cu-replacement and acidification/renaturalization processes
      have also been studied, as well as protein modification strategies that make it
      possible to identify and quantify the contribution of the histidine residues to
      metal coordination. Overall, the data obtained in the present study are
      consistent with a scenario where both isoforms exhibit a clear preference for
      divalent metal ion binding, rather than for Cu coordination, although this
      preference is more pronounced towards cadmium for CeMT2, whereas it is markedly
      clearer towards Zn for CeMT1. The presence of histidines in these MTs is revealed
      to be decisive for their coordination performance. In CeMT1, they contribute to
      the binding of a seventh Zn(II) ion in relation to the M(II)(6)-CeMT2 complexes,
      both when synthesized in the presence of supplemented Zn(II) or Cd(II). In CeMT2,
      the unique C-terminal histidine abolishes the Cu-thionein character that this
      isoform would otherwise exhibit.

PMID- 19860834
TI  - Unusual stability of human neuroglobin at low pH--molecular mechanisms and
      biological significance.
AB  - Neuroglobin (Ngb) is a recently discovered globin that is predominantly expressed
      in the brain, retina and other nerve tissues of human and other vertebrates. Ngb
      has been shown to act as a neuroprotective factor, promoting neuronal survival in
      conditions of hypoxic-ischemic insult, such as those occurring during stroke. In
      this work, the conformational and functional stability of Ngb at acidic pH was
      analyzed, and the results were compared to those obtained with Mb. It was shown
      by spectroscopic and biochemical (limited proteolysis) techniques that, at pH
      2.0, apoNgb is a folded and rigid protein, retaining most of the structural
      features that the protein displays at neutral pH. Conversely, apoMb, under the
      same experimental conditions of acidic pH, is essentially a random coil
      polypeptide. Urea-mediated denaturation studies revealed that the stability
      displayed by apoNgb at pH 2.0 is very similar to that of Mb at pH 7.0. Ngb also
      shows enhanced functional stability as compared with Mb, being capable of heme
      binding over a more acidic pH range than Mb. Furthermore, Ngb reversibly binds
      oxygen at acidic pH, with an affinity that increases as the pH is decreased. It
      is proposed that the acid-stable fold of Ngb depends on the particular amino acid
      composition of the protein polypeptide chain. The functional stability at low pH
      displayed by Ngb was instead shown to be related to hexacoordination of the heme
      group. The biological implications of the unusual acid resistance of the folding
      and function of Ngb are discussed.

PMID- 19860835
TI  - Protein folding and disulfide bond formation in the eukaryotic cell: meeting
      report based on the presentations at the European Network Meeting on Protein
      Folding and Disulfide Bond Formation 2009 (Elsinore, Denmark).
AB  - The endoplasmic reticulum (ER) plays a critical role as a compartment for protein
      folding in eukaryotic cells. Defects in protein folding contribute to a growing
      list of diseases, and advances in our understanding of the molecular details of
      protein folding are helping to provide more efficient ways of producing
      recombinant proteins for industrial and medicinal use. Moreover, research
      performed in recent years has shown the importance of the ER as a signalling
      compartment that contributes to overall cellular homeostasis. Hamlet's castle
      provided a stunning backdrop for the latest European network meeting to discuss
      this subject matter in Elsinore, Denmark, from 3 to 5 June 2009. Organized by
      researchers at the Department of Biology, University of Copenhagen, the meeting
      featured 20 talks by both established names and younger scientists, focusing on
      topics such as oxidative protein folding and maturation (in particular in the ER,
      but also in other compartments), cellular redox regulation, ER-associated
      degradation, and the unfolded protein response. Exciting new advances were
      presented, and the intimate setting with about 50 participants provided an
      excellent opportunity to discuss current key questions in the field.

PMID- 19860836
TI  - Tritium planigraphy study of structural alterations in the coat protein of Potato
      virus X induced by binding of its triple gene block 1 protein to virions.
AB  - Alterations in Potato virus X (PVX) coat protein structure after binding of the
      protein, encoded by the first gene of PVX triple gene block (triple gene block 1
      protein, TGBp1), to the virions were studied using tritium planigraphy.
      Previously, it has been shown that TGBp1 molecules interact with the PVX particle
      end, containing the 5'-terminus of PVX RNA, and that this interaction results in
      a strong decrease in virion stability and its transformation to a translationally
      active state. In this work, it has been shown that the interaction of TGBp1 with
      PVX virions leads to an increase of approximately 50% in tritium label
      incorporation into the 176-198 segment of the 236-residue-long PVX coat protein
      subunit, with some decrease in label incorporation into the N-terminal coat
      protein region. According to the new 'sandwich' variant of our recently proposed
      model of the three-dimensional structure of the intravirus PVX coat protein, the
      176-198 segment is assigned to the beta-sheet region located at the subunit
      surface, presumably participating in coat protein interactions with the
      intravirus RNA and/or in protein-protein interactions, whereas the N-terminal
      coat protein region corresponds to the other part of the same beta-sheet. For the
      remaining segments of the PVX coat protein subunit, no significant difference
      between tritium incorporation into untreated and TGBp1-treated PVX was observed.
      A detailed description of the 'sandwich' version of the intravirus PVX coat
      protein model is presented.

PMID- 19860837
TI  - alpha-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y)
      cells.
AB  - Parkinson's disease (PD) is characterized in part by the presence of alpha
      synuclein (alpha-syn) rich intracellular inclusions (Lewy bodies). Mutations and
      multiplication of the alpha-synuclein gene (SNCA) are associated with familial
      PD. Since Ca2+ dyshomeostasis may play an important role in the pathogenesis of
      PD, we used fluorimetry in fura-2 loaded SH-SY5Y cells to monitor Ca2+
      homeostasis in cells stably transfected with either wild-type alpha-syn, the A53T
      mutant form, the S129D phosphomimetic mutant or with empty vector (which served
      as control). Voltage-gated Ca2+ influx evoked by exposure of cells to 50 mM K+
      was enhanced in cells expressing all three forms of alpha-syn, an effect which
      was due specifically to increased Ca2+ entry via L-type Ca2+ channels.
      Mobilization of Ca2+ by muscarine was not strikingly modified by any of the alpha
      syn forms, but they all reduced capacitative Ca2+ entry following store depletion
      caused either by muscarine or thapsigargin. Emptying of stores with cyclopiazonic
      acid caused similar rises of [Ca2+](i) in all cells tested (with the exception of
      the S129D mutant), and mitochondrial Ca2+ content was unaffected by any form of
      alpha-synuclein. However, only WT alpha-syn transfected cells displayed
      significantly impaired viability. Our findings suggest that alpha-syn regulates
      Ca2+ entry pathways and, consequently, that abnormal alpha-syn levels may promote
      neuronal damage through dysregulation of Ca2+ homeostasis.

PMID- 19860838
TI  - Microglial phagocytosis attenuated by short-term exposure to exogenous ATP
      through P2X receptor action.
AB  - Microglia, the CNS resident macrophages responsible for the clearance of
      degenerating cellular fragments, are essential to tissue remodeling and repair
      after CNS injury. ATP can be released in large amounts after CNS injury and may
      mediate microglial activity through the ionotropic P2X and the metabotropic P2Y
      receptors. This study indicates that exposure to a high concentration of ATP for
      30 min rapidly induces changes of the microglial cytoskeleton, and significantly
      attenuates microglial phagocytosis. A pharmacological approach showed that ATP
      induced inhibition of microglial phagocytotic activity was due to P2X(7)R
      activation, rather than that of P2YR. Activation of P2X(7)R by its agonist, 2'-3'
      O-(4-benzoyl)benzoyl-ATP (BzATP), produced a Ca(2+)-independent reduction in
      microglial phagocytotic activity. In addition, the knockdown of P2X(7)R
      expression by lentiviral-mediated shRNA interference or the blockade of P2X(7)R
      activation by the specific antagonists, oxidized ATP (oxATP) and brilliant blue
      G, has efficiently restored the phagocytotic activity of ATP and BzATP-treated
      microglia. Our results reveal that P2X(7)R activation may induce the formation of
      a Ca(2+)-independent signaling complex, which results in the reduction of
      microglial phagocytosis. This suggests that exposure to ATP for a short-term
      period may cause insufficient clearance of tissue debris by microglia through
      P2X(7)R activation after CNS injury, and that blockade of this receptor may
      preserve the phagocytosis of microglia and facilitate CNS tissue repair.

PMID- 19860839
TI  - Down-regulation of lipocalin 2 contributes to chemoresistance in glioblastoma
      cells.
AB  - Malignant gliomas are the most common primary brain tumor and have a poor
      clinical prognosis. 1, 3-Bis (2-chloroethyl)-1-nitrosourea (BCNU) is an
      alkylating agent that is commonly used in glioma therapy. However, BCNU
      chemotherapy often fails due to drug resistance. To gain better understanding of
      molecular mechanisms underlying the drug resistance of glioma, a BCNU-resistant
      variant (C6R) of C6 rat glioma cells was selected and characterized. The
      established C6R cells were resistant to BCNU-induced cell death and cell cycle
      arrest as confirmed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium
      bromide reduction assay and flow cytometric analysis of DNA content. C6R cells
      showed an increased expression of common drug resistance-related genes such as O6
      methylguanine-DNA methyltransferase and multiple drug resistance 1. In contrast,
      C6R cells showed a decreased expression of glial fibrillary acidic protein,
      therefore, displaying shorter cellular processes compared with parental C6 cells.
      More importantly, in conjunction with the morphological changes, the expression
      of lipocalin-2 (lcn2), a 25-kDa secreted proapoptotic protein, was markedly
      reduced in the BCNU-resistant C6R cells. However, there was no significant change
      in the expression of lcn2 receptors. Addition of recombinant LCN2 protein or
      introduction of lcn2 cDNA significantly increased the sensitivity of C6 cells and
      human glioma cells to BCNU or other anticancer drugs, while knockdown of lcn2
      expression by antisense cDNA transfection decreased the sensitivity. When lcn2
      was re-expressed in C6R cells, the BCNU sensitivity was restored. Lcn2 enhanced
      BCNU-induced Akt dephosphorylation providing a molecular basis of apoptosis
      sensitization. These results suggest that LCN2 protein may be involved in glioma
      drug resistance and may provide a new approach to sensitizing glioblastoma to
      chemotherapy.

PMID- 19860840
TI  - Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more
      sensitive to the apoptotic agent paclitaxel in vitro and in vivo.
AB  - Glypican-3 (GPC3) is a heparan sulfate proteoglycan that is bound to the cell
      membrane by a glycosylphosphatidylinositol (GPI) anchor, and glypicans can
      regulate the activity of a wide variety of growth and survival factors. We report
      here that GPC3 was expressed in clear cell carcinoma of the ovary, and not in
      other carcinomas. To evaluate the phenotype and potential preclinical relevance,
      we generated an ovarian cancer cell line stably transfected with plasmids
      encompassing shRNA targeting GPC3. We show that the clear cell carcinoma cell
      line with silenced GPC3 expression (GPC3 [-]) was more sensitive to paclitaxel
      than GPC3 (+) cells. In addition, the GPC3 silencing induced sensitization to
      paclitaxel was associated with the activation of an apoptosis pathway, as shown
      by flow cytometry. Moreover, we investigated the effect of GPC3 on peritoneal
      metastases using nude mice. Peritoneal metastases caused by GPC3 (-) were more
      sensitive to paclitaxel than those caused by GPC3 (+) cells. These results
      indicate that increased GPC3 expression in a clear cell carcinoma cell line may
      play a protective role against apoptosis, and so the downregulation of GPC3 may
      be a potential target to increase sensitivity to paclitaxel-induced apoptosis in
      clear cell carcinoma.

PMID- 19860841
TI  - Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically
      inhibit proliferation of gallbladder carcinoma.
AB  - Polycomb group protein EZH2, frequently overexpressed in malignant tumors, is the
      catalytic subunit of polycomb repressive complex 2 (PRC2). PRC2 interacts with
      HDACs in transcriptional silencing and relates to tumor suppressor loss. We
      examined the expression of HDAC isoforms (HDAC 1 and 2) and EZH2, and evaluated
      the possible use of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and
      EZH2 repressor for gallbladder carcinoma. We used 48 surgically resected
      gallbladders and cultures of human gallbladder epithelial cells (HGECs),
      gallbladder carcinoma (TGBC2TKB), and cholangiocarcinoma (HuCCT-1 and TFK-1) cell
      lines for examination. Immunohistochemically, EZH2 was overexpressed in
      gallbladder carcinoma, especially poorly differentiated carcinoma, but not in
      normal epithelium. In contrast, HDAC1/2 were expressed in both carcinoma and
      normal epithelium in vivo. This pattern was verified in cultured cells; EZH2 was
      highly expressed only in TGBC2TKB, whereas HDAC1/2 were expressed in HGECs and
      TGBC2TKB. Interestingly, SAHA treatment caused significant cell number decline in
      three carcinoma cells, and this effect was synergized with EZH2 siRNA treatment;
      however, HGECs were resistant to SAHA. In TGBC2TKB cells, the expression of EZH2
      and HDAC1/2 were decreased by SAHA treatment, and p16(INK4a), E-cadherin, and
      p21were simultaneously activated; however, no such findings were obtained in
      HGECs, suggesting that the effect of SAHA depends on the EZH2-mediated tumor
      suppressor loss. In conclusion, this study suggests a possible mechanism by which
      carcinoma cells but not normal cells are sensitive to SAHA and indicates the
      efficacy of this new anticancer agent in combination with EZH2 repression in
      gallbladder carcinoma.

PMID- 19860842
TI  - Knock down of the dual functional protein apurinic /apyrimidinic endonuclease 1
      enhances the killing effect of hematoporphrphyrin derivative-mediated
      photodynamic therapy on non-small cell lung cancer cells in vitro and in a
      xenograft model.
AB  - Photodynamic therapy (PDT) is considered to be effective treatment for many
      cancers including lung cancer, head and neck cancers, and prostate cancer. It
      uses the combination of nontoxic photosensitizers and harmless visible light to
      generate reactive oxygen species and kill cells. However, DNA repair and reactive
      oxygen species-induced signaling pathway activation play crucial roles in
      cellular response to PDT and may also result in therapeutic limitation of PDT. To
      improve the cancer therapeutic efficacy of PDT, we targeted apurinic/apyrimidinic
      endonuclease (APE1), which is essential for both DNA repair and redox regulation
      of gene transcription, as a potential candidate for PDT combined gene therapy. In
      our study, an adenovirus-mediated APE1 silencing strategy was introduced to test
      its therapeutic enhancement for the non-small cell lung cancer cell line A549
      both in vitro and in vivo after hematoporphrphyrin derivative (HpD)-mediated PDT.
      The adenovirus vector Ad5/F35-shAPE1 was validated to significantly suppress the
      protein expression of APE1 in cultured A549 cell and in its xenograft of nude
      mice. Ad5/F35-shAPE1 effectively inhibited APE1 protein upregulation induced by
      PDT and resulted in an increase in A549 cell killing by photoirradiation compared
      with the hematoporphrphyrin derivative-PDT alone group. Ad5/F35-shAPE1 suppressed
      the DNA repair capacity for single-strand breaks and abolished the activation of
      some stress-related transcription factors such as hypoxia-induced factor (HIF)-1
      that consequently lead to increased cell apoptosis after PDT. Additionally, knock
      down of APE1 enhanced the tumor suppression efficacy of PDT on the A549
      xenograft. Our study indicated that APE1-targeted gene therapy combined with PDT
      is a promising strategy for enhancement of the efficacy of PDT in treatment of
      non-small cell lung cancer.

PMID- 19860843
TI  - Role of syndecan-1 (CD138) in cell survival of human urothelial carcinoma.
AB  - Heparan sulfate proteoglycan syndecan-1, CD138, is well known to be associated
      with cell proliferation, adhesion, and migration in various types of
      malignancies. In the present study, we focused on the role of syndecan-1 in human
      urothelial carcinoma of the urinary bladder. Silencing of syndecan-1 by siRNA
      transfection down-regulated transcriptional factor junB and the long isoform of
      FLICE-inhibitory protein (FLIP long), resulting in the induction of apoptosis in
      the urothelial carcinoma cell lines UMUC2 and UMUC3. Knockdown of junB and FLIP
      long as well as syndecan-1 silencing mediated apoptosis that was inhibited by pan
      caspase inhibitors. Transurethral injection of syndecan-1 siRNA into the urinary
      bladder significantly reduced syndecan-1 gene expression and growth of red
      fluorescent-labeled KU-7/RFP bladder cancer cells in the mouse orthotopic bladder
      cancer model. Immunohistochemical examination showed high syndecan-1 protein
      expression in high-grade, superficial, and deep invasive carcinomas (pT1 and
      >or=pT2) as well as carcinoma in situ, but not in low-grade and noninvasive
      phenotypes (pTa). In addition, the percentage of cancer cells positive for
      syndecan-1 at initial diagnosis was statistically associated with the frequency
      of bladder cancer recurrence after transurethral resection. In conclusion,
      syndecan-1 might contribute to urothelial carcinoma cell survival and
      progression; therefore, this molecule could be a new therapeutic target in human
      urinary bladder cancer.

PMID- 19860844
TI  - Steroid and xenobiotic receptor in human esophageal squamous cell carcinoma: a
      potent prognostic factor.
AB  - Steroid and xenobiotic receptor (SXR) is a nuclear receptor activated by diverse
      exogenous and endogenous compounds and has been demonstrated to play a pivotal
      role in detoxification through its regulation of various metabolizing enzymes and
      transporters. Recent studies also demonstrated the potential roles of SXR in the
      regulation of apoptosis and inflammation in various carcinoma cells, but the
      status of SXR in human esophageal squamous cell carcinoma (ESCC) has not been
      examined. Therefore, in this study, we performed immunohistochemical and
      quantitative RT-PCR evaluations in human ESCC in order to clarify its biological
      and clinical significance. We first immunolocalized SXR in 73 human ESCC cases.
      SXR immunoreactivity was detected in the nuclei, or in both nuclei and cytoplasm
      of carcinoma cells (98%, 20% of cases, respectively). The status of nuclear SXR
      immunoreactivity was inversely correlated with histological grade, lymph node
      status, ki67/MIB1 labeling index, and positively correlated with retinoid X
      receptor alpha status. In addition, high nuclear SXR expression was significantly
      correlated with favorable clinical outcome of the patients. Multivariate analysis
      further demonstrated SXR status in carcinoma cells as an independent favorable
      prognostic factor of the patients. Results of quantitative RT-PCR study
      demonstrated that SXR mRNA expression was detected in three of five cases, and
      was marked higher in the cancerous tissue than non-neoplastic tissue of these
      patients. This is the first study to demonstrate the status of SXR in human ESCC
      and the results suggest that SXR is a potent favorable prognostic factor of human
      ESCC.

PMID- 19860845
TI  - CD24-dependent MAPK pathway activation is required for colorectal cancer cell
      proliferation.
AB  - CD24 is a glycosylphosphatidylinositol-anchored membrane protein reported to be
      overexpressed in human tumorigenesis and progression. Our purpose was to
      determine the role of CD24 in the proliferation of colorectal cancer cells and
      the potential mechanisms in this process. Our data showed that CD24 promoted cell
      growth and induced activation of extracellular signal-regulated kinases, Raf-1,
      and p38 mitogen-activated protein kinase. Furthermore, suppression of
      extracellular signal-regulated kinases and p38 mitogen-activated protein kinase
      activity by their specific inhibitors, U0126 and SB203580, abrogated CD24-induced
      proliferation in vitro. By tumorigenicity assay in female BALB/c nude mice, we
      further demonstrated that CD24 promoted tumor growth in vivo. Immunohistochemical
      analysis revealed that CD24 expression occurred in 92.5% of human colorectal
      cancer tissue, and increased with tumor progression. More importantly, the
      stainings of phospho-extracellular signal-regulated kinases and phospho-p38
      mitogen-activated protein kinase were strongly correlated with CD24 expression.
      Taken together, our data suggest that CD24-dependent extracellular signal
      regulated kinases and p38 mitogen-activated protein kinase activations are
      required for colorectal cancer cell proliferation in vitro and in vivo. The
      linkage of CD24 and the mitogen-activated protein kinase pathway may unravel a
      novel mechanism in the regulation of colorectal cancer proliferation.

PMID- 19860846
TI  - It takes two to tango: combinations of conventional cytotoxics with compounds
      targeting the vascular endothelial growth factor-vascular endothelial growth
      factor receptor pathway in patients with solid malignancies.
AB  - Through advances in molecular biology, insight into the mechanisms driving
      malignancies has improved immensely and as a result, various factors playing an
      essential role in the biology of numerous tumor types have been revealed. By
      using compounds that specifically block the function of a single factor being
      crucial for tumor pathogenesis, it was hoped to exert antitumor activity while
      avoiding toxicities characteristic for conventional chemotherapy. One of the
      processes of crucial importance in the development of cancer, and consequently an
      attractive target, is angiogenesis. In recent years, several key factors for
      angiogenesis have been identified, including ligands, receptors, and transduction
      signaling factors. Of these, the vascular endothelial growth factor (VEGF)
      pathway has been found to be activated in numerous tumor types and considered one
      of the main drivers of angiogenesis. Roughly, VEGF-mediated angiogenesis can be
      inhibited by two approaches: either by monoclonal antibodies directed towards
      VEGF or its corresponding receptors, or by kinase inhibitors targeting the signal
      transduction of the VEGF receptors. As monotherapy, several kinase inhibitors
      exert antitumor activity in tumor types such as renal cell carcinoma. However, in
      most tumor types, the antitumor activity of compounds targeting the VEGF pathway
      is limited. In recent years, evidence is mounting that the paradigm of one single
      factor that drives malignant behavior applies rarely and is an oversimplification
      for most tumors in which there are multiple driving pathways. Consequently,
      multitargeting rather than single-targeting approaches are required. One of the
      means is by combining targeted agents with conventional cytotoxics. As the VEGF
      pathway also affects the sensitivity of tumor cells to chemotherapeutics,
      combinations of compounds targeting this pathway and conventional cytotoxics have
      been explored. This review addresses such combinations.

PMID- 19860847
TI  - Soy product and isoflavone intake and breast cancer risk defined by hormone
      receptor status.
AB  - The association between soy food consumption and breast cancer risk has been
      inconsistent. A hospital-based case-control study was conducted to assess the
      relationship between soy food intake and breast cancer risk according to the
      estrogen receptor (ER) and/or progesterone receptor (PR) status of breast cancer
      in Chinese women residing in Guangdong province from June 2007 to August 2008. A
      total of 438 consecutively recruited cases with primary breast cancer were
      frequency matched to 438 controls by age (5-year interval) and residence
      (rural/urban). Dietary intake was assessed by face-to-face interviews using a
      validated food frequency questionnaire. Odds ratios (OR) and 95% confidence
      intervals (CI) were obtained by using multiple unconditional logistic regression
      adjusted for the potential confounders. We observed a statistically significant
      inverse association between soy isoflavone and soy protein intake with breast
      cancer risk. The multivariate ORs (95% CIs) of breast cancer risk for the highest
      quartile compared with the lowest quartile were 0.54 (0.34-0.84) for soy
      isoflavone and 0.62 (0.40-0.96) for soy protein, respectively. A preventive
      effect of soy food was found for all subtypes of ER and/or PR status of breast
      cancer. The inverse association was more evident among premenopausal women. This
      study suggests that consumption of soy food, soy isoflavone, is inversely
      associated with the risk of breast cancer. The protective effects of soy did not
      seem to differ by ER and PR breast cancer status.

PMID- 19860848
TI  - Fresh and pickled vegetable consumption and gastric cancer in Japanese and Korean
      populations: a meta-analysis of observational studies.
AB  - It is widely known that vegetable consumption contributes to reducing the risk of
      gastric cancer (GC). However, the incidence rates of GC remain high in both
      Japanese and Korean populations, even though they have a high consumption of
      total vegetables. This may be due to the fact that Japanese and Koreans mainly
      consume processed vegetables, such as cooked, salted, or pickled vegetables,
      rather than fresh vegetables. To determine whether the intakes of fresh and
      pickled vegetables have different effects on the risk of GC in Japanese and
      Korean populations, we carried out a meta-analysis of published epidemiological
      reports. Eight studies on the consumption of fresh vegetables and 14 studies on
      the consumption of pickled vegetables related to GC risk were included in this
      meta-analysis. Four studies exploring differences in GC risk in men and women
      were considered separately. We observed that a high intake of fresh vegetables
      was significantly associated with a decreased risk of GC (overall summary OR =
      0.62, 95% CI = 0.46-0.85) but that a high intake of pickled vegetables was
      significantly associated with an increased risk of GC (overall summary OR = 1.28,
      95% CI = 1.06-1.53). The results of this meta-analysis provide evidence that a
      high intake of pickled vegetables may increase GC risk and suggest that a high
      consumption of fresh vegetables, rather than a large total amount of vegetables
      including pickled vegetables, is important to reduce GC risk.

PMID- 19860849
TI  - Overexpression and involvement of special AT-rich sequence binding protein 1 in
      multidrug resistance in human breast carcinoma cells.
AB  - Special AT-rich sequence binding protein (SATB) 1 has been proposed to act as a
      determinant for the acquisition of metastatic activity by controlling expression
      of a specific set of genes that promote metastatic activity. Here we found that
      SATB1 expression is upregulated in multidrug-resistant breast cancer cells that
      exhibit higher invasive potential than the parental cells. Apart from
      accelerating metastasis and inducing epithelial-mesenchymal transition, SATB1 was
      demonstrated to confer resistance to both P-glycoprotein-related and P
      glycoprotein-non-related drugs on MCF7 cells, which was accompanied by decreasing
      accumulation of adriamycin in SATB1-overexpressing transfectants. SATB1 depletion
      could partially reverse the multidrug resistance (MDR) phenotype of MCF7/ADR in
      vitro and in vivo. The SATB1-induced P-glycoprotein-mediated MDR could be
      reversed by treatment with anti-P-glycoprotein mAb. Moreover, SATB1 plays an
      important role in anti-apoptotic activity in MCF7/ADR cells in response to
      adriamycin treatment, which suggests another mechanism contributing to SATB1
      related MDR of breast cancers. These data provide new insights into the mode by
      which breast tumors acquire the MDR phenotype and also imply a role for SATB1 in
      this process.

PMID- 19860850
TI  - Potential for therapeutic targeting of tumor stem cells.
AB  - Recent developments in isolation and characterization of tumor stem cells (TSCs)
      have opened new possibilities for developing TSC-targeted therapies. Extensive
      efforts have been made to ascertain markers of TSCs, including cell surface,
      enzymatic, gene expression profile, and functional markers. These markers and the
      technologies used to identify and isolate TSCs are discussed in this review. TSC
      characteristics, such as quiescence, multidrug resistance, enhanced DNA repair
      ability, and anti-apoptotic mechanisms, and various features of the in vivo
      niche, which may make them resistant to conventional therapy, are also discussed
      here. The increasing understanding of aberrantly expressed molecules and
      signaling pathways in TSCs may provide the foundation for design of therapeutic
      strategies for TSC ablation.

PMID- 19860851
TI  - Changes in cholesterol biosynthetic and transport pathways after excitotoxicity.
AB  - The present study was carried out to elucidate changes in the gene expression and
      activity of cholesterol biosynthetic enzymes and transporters in the rat
      hippocampus after kainate excitotoxicity. Significantly increased cholesterol
      level was detected in the degenerating hippocampus, reaching double normal levels
      at 1 week after kainate injury. RT-PCR analyses of hippocampal homogenates showed
      significantly decreased mRNA expression of the transcription factor controlling
      cholesterol biosynthesis SREBP-2, and the rate-controlling enzyme HMG-CoA (3
      hydroxy-3-methyl-glutaryl-CoA) reductase at all time points after kainate
      injection; and decreased lanosterol synthase and CYP51 at 1 and 2 weeks post
      kainate injection respectively. GC-MS analyses showed a significant increase in
      cholesterol biosynthetic precursors lanosterol, desmosterol and 7
      dehydrocholesterol at 1 day after kainate injection presumably reflecting
      biosysnthesis in injured neurons, and significant decreases in precursors at 1
      and 2 weeks post-kainate injection, at time of gliosis in the degenerating
      hippocampus. Levels of cholesterol autooxidation including 7 ketocholesterol and
      cholesterol epoxides were elevated in the kainate lesioned hippocampus.
      Furthermore, loss of expression of the cholesterol transporter, ABCA1 was
      detected in neurons, but increased expression in astrocytes was detected after
      kainate lesions. The results suggest that increased cholesterol biosynthesis and
      loss of ABCA1 expression in injured neurons might result in increase in
      cholesterol in the degenerating hippocampus. The increased cholesterol might
      predispose to increased formation of cholesterol oxidation products which have
      been shown to be toxic to neurons.

PMID- 19860852
TI  - Activation of PERK kinase in neural cells by proteasome inhibitor treatment.
AB  - Inhibition of the proteasome proteolytic pathway occurs as the result of normal
      aging, as well as in a variety of neurodegenerative conditions, and is believed
      to promote cellular toxicity in each of these conditions through diverse
      mechanisms. In the present study, we examined whether proteasome inhibition
      alters the protein kinase receptor-like endoplasmic reticulum kinase (PERK). Our
      studies demonstrate that proteasome inhibitors induce the transient activation of
      PERK in both primary rat neurons as well as the N2a neural cell line. Experiments
      with siRNA to PERK demonstrated that the modulation of PERK was not significant
      involved in regulating toxicity, ubiquitinated protein levels, or ribosome
      perturbations in response to proteasome inhibitor treatment. Surprisingly, PERK
      was observed to be involved in the up-regulation of p38 kinase following
      proteasome inhibitor treatment. Taken together, these data demonstrate the
      ability of proteasome inhibition to activate PERK and demonstrate evidence for
      novel cross-talk between PERK and the activation of p38 kinase in neural cells
      following proteasome inhibition. Taken together, these data have implications for
      understanding the basis by which proteasome inhibition alters neural homeostasis,
      and the basis by which cell signaling cascades are regulated by proteasome
      inhibition.

PMID- 19860853
TI  - Elevated sulfatide levels in neurons cause lethal audiogenic seizures in mice.
AB  - Galactosylceramide (GalCer) and 3-O-sulfo-GalCer (sulfatide) are abundant
      sphingolipids in myelinating glial cells. However, low levels of GalCer and
      sulfatide have also been found in neurons, though their physiological role in
      these cells is unknown. Transgenic mice over-expressing UDP-galactose : ceramide
      galactosyltransferase (CGT) under control of the Thy1.2 promoter synthesize C18 :
      0 fatty acid containing GalCer and sulfatide in neurons. Depending on the genetic
      background, these transgenic mice have a significantly reduced life span.
      Transgenic mice were extremely sensitive to sound stimuli and displayed lethal
      audiogenic seizures after relatively mild acoustic stimulation, i.e., key
      jangling. CGT-transgenic mice additionally over-expressing the adenosine 3'
      phospho 5'-phosphosulfate : cerebroside sulfotransferase were more sensitive to
      audiogenic seizure induction than mice expressing only the CGT-transgene. This
      correlated with the higher sulfatide content in neuronal plasma membranes of the
      double-transgenic mice compared with CGT-transgenic mice, and strongly suggests
      that lethal audiogenic seizures are caused by elevated sulfatide levels in
      transgenic neurons. CGT-transgenic mice will be a useful model to further
      investigate how sulfatide affects functional properties of neurons.

PMID- 19860854
TI  - Modulation of Aanat gene transcription in the rat pineal gland.
AB  - The main function of the rat pineal gland is to transform the circadian rhythm
      generated in the suprachiasmatic nucleus into a rhythmic signal of circulating
      melatonin characterized by a large nocturnal increase that closely reflects the
      duration of night period. This is achieved through the tight coupling between
      environmental lighting and the expression of arylalkylamine-N-acetyltransferase,
      the rhythm-controlling enzyme in melatonin synthesis. The initiation of Aanat
      transcription at night is controlled largely by the norepinephrine-stimulated
      phosphorylation of cAMP response element-binding protein by protein kinase A.
      However, to accurately reflect the duration of darkness, additional signaling
      mechanisms also participate to fine-tune the temporal profile of adrenergic
      induced Aanat transcription. Here, we reviewed some of these signaling
      mechanisms, with emphasis on the more recent findings. These signaling mechanisms
      can be divided into two groups: those involving modification of constitutively
      expressed proteins and those requiring synthesis of new proteins. This review
      highlights the pineal gland as an excellent model system for studying
      neurotransmitter-regulated rhythmic gene expression.

PMID- 19860855
TI  - Structural and functional characterization of a novel FE65 protein product up
      regulated in cognitively impaired FE65 knockout mice.
AB  - FE65 is a multi-modular adaptor protein that binds the cytoplasmic tail of the
      beta-amyloid precursor protein (APP). Genetic evidence suggests that APP is
      intimately involved in the pathogenesis of dementias of the Alzheimer type,
      neurodegenerative disorders that affect multiple cognitive domains, including
      learning and memory. Evidence from p97FE65-specific knockout mice (lacking the 97
      kDa full-length FE65 protein, p97FE65) suggests an important role for FE65 in
      learning and memory. Interpretation of the learning and memory phenotype,
      however, is complicated by the up-regulation (compared with wild-type mice) of a
      novel 60 kDa FE65 isoform (p60FE65). Here, we report an evidence that p60FE65 is
      translated from an alternative methionine, M261, on the p97FE65 transcript. Thus,
      p60FE65 has a shortened N-terminus, lacking part of the WW domain that is
      considered important for nuclear translocation and transactivation of gene
      expression. Consistently, p60FE65 exhibits an attenuated ability for APP-Gal4
      mediated transcription as compared with p97FE65. Similar to p97FE65, however,
      both transfected and endogenous p60FE65 are able to translocate to the nucleus in
      cultured cells and in neurons. These results are consistent with earlier evidence
      from our laboratory that reduced FE65 nuclear signaling may contribute, in part,
      to the phenotypes observed in p97FE65 knockout mice.

PMID- 19860856
TI  - Photoperiodic regulation of retinoic acid signaling in the hypothalamus.
AB  - Both retinoic acid (RA) and thyroid hormone (TH) regulate transcription via
      specific nuclear receptors. TH regulates hypothalamic homeostasis and active T3
      is generated by deiodinase enzymes in tanycytes surrounding the third ventricle.
      However, RA has not been previously considered in such a role. Data presented
      here highlights novel parallels between the TH and RA synthetic pathways in the
      hypothalamus implying that RA also acts to regulate hypothalamic gene expression
      and function. Key elements of the RA cellular signaling pathway were shown to be
      regulated in the rodent hypothalamus. Retinoid synthetic enzymes and the retinol
      transport protein Stra6 were located in the cells lining the third ventricle
      allowing synthesis of RA from retinol present in the CNS to act via RA receptors
      and retinoid X receptors in the hypothalamus. Photoperiod manipulation was shown
      to alter the expression of synthetic enzymes and receptors with lengthening of
      photoperiod leading to enhanced RA signaling. In vitro RA can regulate the
      hypothalamic neuroendocrine peptide adrenocorticotrophic hormone. This work
      presents the new concept of controlled RA synthesis by hypothalamic tanycytes
      giving rise to possible involvement of this system in endocrine, and possibly
      vitamin A, homeostasis.

PMID- 19860857
TI  - The PDZ domain protein CAL interacts with mGluR5a and modulates receptor
      expression.
AB  - In this study, we investigated the association of metabotropic glutamate receptor
      subtype-5a (mGluR5a) with cystic fibrosis transmembrane conductance regulator
      associated ligand (CAL). Using glutathione-S-transferase pull-down techniques, we
      found that mGluR5a directly interacted with CAL, with the C-terminus of the
      receptor binding to the PSD95/Discslarge/ZO-1 homology domain of CAL. The last
      four amino acids (S-S-S-L) of the C-terminus of the receptor were essential
      determinants for the interaction. Co-immunoprecipitation experiments and
      immunofluorescence assays revealed that full-length mGluR5a also associated with
      intact CAL in vivo, an observation consistent with the results from studies on
      fragment interactions in vitro. Functionally, upon co-expression with mGluR5a,
      CAL profoundly inhibited the ubiquitination of mGluR5a and enhanced receptor
      expression at the protein level but not at the mRNA level. These findings reveal
      that mGluR5a protein expression is physiologically regulated via its interaction
      with CAL. These results also suggest a molecular mechanism by which mGluR5a
      protein expression may be regulated at the post-translational level by the CAL
      protein, possibly by blocking ubiquitination-dependent receptor degradation.

PMID- 19860858
TI  - Combinatorial interaction between two human serotonin transporter gene variable
      number tandem repeats and their regulation by CTCF.
AB  - Two distinct variable number tandem repeats (VNTRs) within the human serotonin
      transporter gene (SLC6A4) have been implicated as predisposing factors for CNS
      disorders. The linked polymorphic region in the 5'-promoter exists as short (s)
      and long (l) alleles of a 22 or 23 bp elements. The second within intron 2
      (Stin2) exists as three variants containing 9, 10 or 12 copies of a 16 or 17 bp
      element. These VNTRs, individually or in combination, supported differential
      reporter gene expression in rat neonate prefrontal cortical cultures. The level
      of reporter gene activity from the dual VNTR constructs indicated combinatorial
      action between the two domains. Chromatin immunoprecipitation demonstrated that
      both these VNTR domains can bind the CCCTC-binding factor and this correlated
      with the ability of exogenously supplied CCCTC-binding factor to modulate the
      expression supported by these reporter gene constructs. We suggest that the
      potential for interaction between multiple polymorphic domains should be
      incorporated into genetic association studies.

PMID- 19860860
TI  - Nature and consequences of mammalian brain and CSF efflux transporters: four
      decades of progress.
AB  - In the last 40 years, especially with the application of new neurochemical and
      molecular biological techniques, there has been explosive progress in
      understanding how certain ligands and drugs are transported across the blood
      brain barrier and choroid plexus out of brain and CSF. In the CNS, there are
      several separate efflux transporters with very broad specificity that are
      responsible for much of the efflux transport. This review focuses on three such
      transporters: organic acid transporter-3, peptide transporter-2 and P
      glycoprotein for which there is substantial new information including 'knockout'
      models in mice and, in one case, dogs. Moreover, the structural biology and
      transport mechanism of P-glycoprotein at 3.8 angstroms is described. The overall
      objective is to show how this new knowledge provides a more thorough
      understanding (e.g., of molecular mechanisms) of efflux transport and in several
      cases leads to clinically relevant information that allows better treatment of
      certain CNS disorders (e.g., meningitis and brain cancer).

PMID- 19860859
TI  - A novel role for calcium/calmodulin kinase II within the brainstem
      pedunculopontine tegmentum for the regulation of wakefulness and rapid eye
      movement sleep.
AB  - Considerable evidence suggests that the brainstem pedunculopontine tegmentum
      (PPT) neurons are critically involved in the regulation of rapid eye movement
      (REM) sleep and wakefulness (W); however, the molecular mechanisms operating
      within the PPT to regulate these two behavioral states remain relatively unknown.
      Here we demonstrate that the levels of calcium/calmodulin kinase II (CaMKII) and
      phosphorylated CaMKII expression in the PPT decreased and increased with 'low W
      with high REM sleep' and 'high W/low REM sleep' periods, respectively. These
      state-specific expression changes were not observed in the cortex, or in the
      immediately adjacent medial pontine reticular formation. Next, we demonstrate
      that CaMKII activity in the PPT is negatively and positively correlated with the
      'low W with high REM sleep' and 'high W/low REM sleep' periods, respectively.
      These differences in correlations were not seen in the medial pontine reticular
      formation CaMKII activity. Finally, we demonstrate that with increased PPT CaMKII
      activity observed during high W/low REM sleep, there were marked shifts in the
      expression of genes that are involved in components of various signal
      transduction pathways. Collectively, these results for the first time suggest
      that the increased CaMKII activity within PPT neurons is associated with
      increased W at the expense of REM sleep, and this process is accomplished through
      the activation of a specific gene expression profile.

PMID- 19860864
TI  - Abstracts of the Danish Society for Emergency Medicine: Research Symposium 2009.
      Copenhagen, Denmark. April 26, 2009.

PMID- 19860861
TI  - Insulin/PI3K signaling protects dentate neurons from oxygen-glucose deprivation
      in organotypic slice cultures.
AB  - It is known that ischemia/reperfusion induces neurodegeneration in the
      hippocampus in a subregion-dependent manner. This study investigated the
      mechanism of selective resistance/vulnerability to oxygen-glucose deprivation
      (OGD) using mouse organotypic hippocampal cultures. Analysis of propidium iodide
      uptake showed that OGD-induced duration- and subregion-dependent neuronal injury.
      When compared with the CA1-3 subregions, dentate neuronal survival was more
      sensitive to inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling
      under basal conditions. Dentate neuronal sensitivity to PI3K/Akt signaling
      activation was inversely related to its vulnerability to OGD-induced injury;
      insulin/insulin-like growth factor 1 pre-treatment conferred neuroprotection to
      dentate neurons via activation of PI3K/Akt signaling. In contrast, CA1 and CA3
      neurons were less sensitive to disruptions of endogenous PI3K/Akt signaling and
      protective effects of insulin/insulin-like growth factor 1, but more vulnerable
      to OGD. OGD-induced injury in CA1 was reduced by inhibition of NMDA receptor or
      mitogen-activated protein kinase signaling, and was prevented by blocking NMDA
      receptor in the presence of insulin. The CA2 subregion was distinctive in its
      response to glutamate, OGD, and insulin, compared with other CA subregions. CA2
      neurons were sensitive to the protective effects of insulin against OGD-induced
      injury, but more resistant to glutamate. Distinctive distribution of insulin
      receptor beta and basal phospho-Akt was detected in our slice cultures. Our
      results suggest a role for insulin signaling in subregional
      resistance/vulnerability to cerebral ischemia.

PMID- 19860865
TI  - Genetic and pharmacological inhibition of calcineurin corrects the BDNF transport
      defect in Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is an inherited neurogenerative disease
      caused by an abnormal expansion of glutamine repeats in the huntingtin protein.
      There is currently no treatment to prevent the neurodegeneration caused by this
      devastating disorder. Huntingtin has been shown to be a positive regulator of
      vesicular transport, particularly for neurotrophins such as brain-derived
      neurotrophic factor (BDNF). This function is lost in patients with HD, resulting
      in a decrease in neurotrophic support and subsequent neuronal death. One
      promising line of treatment is therefore the restoration of huntingtin function
      in BDNF transport. RESULTS: The phosphorylation of huntingtin at serine 421
      (S421) restores its function in axonal transport. We therefore investigated
      whether inhibition of calcineurin, the bona fide huntingtin S421 phosphatase,
      restored the transport defects observed in HD. We found that pharmacological
      inhibition of calcineurin by FK506 led to sustained phosphorylation of mutant
      huntingtin at S421. FK506 restored BDNF transport in two complementary models:
      rat primary neuronal cultures expressing mutant huntingtin and mouse cortical
      neurons from Hdh(Q111/Q111) HD knock-in mice. This effect was the result of
      specific calcineurin inhibition, as calcineurin silencing restored both
      anterograde and retrograde transport in neurons from Hdh(Q111/Q111) mice. We also
      observed a specific increase in calcineurin activity in the brain of
      Hdh(Q111/Q111) mice potentially accounting for the selective loss of huntingtin
      phosphorylation and contributing to neuronal cell death in HD. CONCLUSION: Our
      results validate calcineurin as a target for the treatment of HD and provide the
      first demonstration of the restoration of huntingtin function by an FDA-approved
      compound.

PMID- 19860866
TI  - Gene ARMADA: an integrated multi-analysis platform for microarray data
      implemented in MATLAB.
AB  - BACKGROUND: The microarray data analysis realm is ever growing through the
      development of various tools, open source and commercial. However there is
      absence of predefined rational algorithmic analysis workflows or batch
      standardized processing to incorporate all steps, from raw data import up to the
      derivation of significantly differentially expressed gene lists. This absence
      obfuscates the analytical procedure and obstructs the massive comparative
      processing of genomic microarray datasets. Moreover, the solutions provided,
      heavily depend on the programming skills of the user, whereas in the case of GUI
      embedded solutions, they do not provide direct support of various raw image
      analysis formats or a versatile and simultaneously flexible combination of signal
      processing methods. RESULTS: We describe here Gene ARMADA (Automated Robust
      MicroArray Data Analysis), a MATLAB implemented platform with a Graphical User
      Interface. This suite integrates all steps of microarray data analysis including
      automated data import, noise correction and filtering, normalization, statistical
      selection of differentially expressed genes, clustering, classification and
      annotation. In its current version, Gene ARMADA fully supports 2 coloured cDNA
      and Affymetrix oligonucleotide arrays, plus custom arrays for which experimental
      details are given in tabular form (Excel spreadsheet, comma separated values, tab
      delimited text formats). It also supports the analysis of already processed
      results through its versatile import editor. Besides being fully automated, Gene
      ARMADA incorporates numerous functionalities of the Statistics and Bioinformatics
      Toolboxes of MATLAB. In addition, it provides numerous visualization and
      exploration tools plus customizable export data formats for seamless integration
      by other analysis tools or MATLAB, for further processing. Gene ARMADA requires
      MATLAB 7.4 (R2007a) or higher and is also distributed as a stand-alone
      application with MATLAB Component Runtime. CONCLUSION: Gene ARMADA provides a
      highly adaptable, integrative, yet flexible tool which can be used for automated
      quality control, analysis, annotation and visualization of microarray data,
      constituting a starting point for further data interpretation and integration
      with numerous other tools.

PMID- 19860867
TI  - Time series analysis of dengue fever and weather in Guangzhou, China.
AB  - BACKGROUND: Monitoring and predicting dengue incidence facilitates early public
      health responses to minimize morbidity and mortality. Weather variables are
      potential predictors of dengue incidence. This study explored the impact of
      weather variability on the transmission of dengue fever in the subtropical city
      of Guangzhou, China. METHODS: Time series Poisson regression analysis was
      performed using data on monthly weather variables and monthly notified cases of
      dengue fever in Guangzhou, China for the period of 2001-2006. Estimates of the
      Poisson model parameters was implemented using the Generalized Estimating
      Equation (GEE) approach; the quasi-likelihood based information criterion (QICu)
      was used to select the most parsimonious model. RESULTS: Two best fitting models,
      with the smallest QICu values, are selected to characterize the relationship
      between monthly dengue incidence and weather variables. Minimum temperature and
      wind velocity are significant predictors of dengue incidence. Further inclusion
      of minimum humidity in the model provides a better fit. CONCLUSION: Minimum
      temperature and minimum humidity, at a lag of one month, are positively
      associated with dengue incidence in the subtropical city of Guangzhou, China.
      Wind velocity is inversely associated with dengue incidence of the same month.
      These findings should be considered in the prediction of future patterns of
      dengue transmission.

PMID- 19860868
TI  - Relatedness facilitates cooperation in the subsocial spider, Stegodyphus
      tentoriicola.
AB  - BACKGROUND: Cooperative hunting and foraging in spiders is rare and prone to
      cheating such that the actions of selfish individuals negatively affect the whole
      group. The resulting social dilemma may be mitigated by kin selection since
      related individuals lose indirect fitness benefits by acting selfishly. Indeed,
      cooperation with genetic kin reduces the disadvantages of within-group
      competition in the subsocial spider Stegodyphus lineatus, supporting the
      hypothesis that high relatedness is an important pre-adaptation in the transition
      to sociality in spiders. In this study we examined the consequences of group size
      and relatedness on cooperative feeding in the subsocial spider S. tentoriicola, a
      species suggested to be at the transition to permanent sociality. RESULTS: We
      formed groups of 3 and 6 spiders that were either siblings or non-siblings. We
      found that increasing group size negatively affected feeding efficiency but that
      these negative effects were reduced in sib-groups. Sib groups were more likely to
      feed cooperatively and all group members grew more homogenously than groups of
      unrelated spiders. The measured differences did not translate into differential
      growth or mortality during the experimental period of 8 weeks. CONCLUSION: The
      combination of our results with those from previous studies indicates that the
      conflict between individual interests and group interests may be reduced by
      nepotism and that the latter promote the maintenance of the social community.

PMID- 19860870
TI  - Minute ventilation of cyclists, car and bus passengers: an experimental study.
AB  - BACKGROUND: Differences in minute ventilation between cyclists, pedestrians and
      other commuters influence inhaled doses of air pollution. This study estimates
      minute ventilation of cyclists, car and bus passengers, as part of a study on
      health effects of commuters' exposure to air pollutants. METHODS: Thirty-four
      participants performed a submaximal test on a bicycle ergometer, during which
      heart rate and minute ventilation were measured simultaneously at increasing
      cycling intensity. Individual regression equations were calculated between heart
      rate and the natural log of minute ventilation. Heart rates were recorded during
      280 two hour trips by bicycle, bus and car and were calculated into minute
      ventilation levels using the individual regression coefficients. RESULTS: Minute
      ventilation during bicycle rides were on average 2.1 times higher than in the car
      (individual range from 1.3 to 5.3) and 2.0 times higher than in the bus
      (individual range from 1.3 to 5.1). The ratio of minute ventilation of cycling
      compared to travelling by bus or car was higher in women than in men. Substantial
      differences in regression equations were found between individuals. The use of
      individual regression equations instead of average regression equations resulted
      in substantially better predictions of individual minute ventilations.
      CONCLUSION: The comparability of the gender-specific overall regression equations
      linking heart rate and minute ventilation with one previous American study,
      supports that for studies on the group level overall equations can be used. For
      estimating individual doses, the use of individual regression coefficients
      provides more precise data. Minute ventilation levels of cyclists are on average
      two times higher than of bus and car passengers, consistent with the ratio found
      in one small previous study of young adults. The study illustrates the importance
      of inclusion of minute ventilation data in comparing air pollution doses between
      different modes of transport.

PMID- 19860869
TI  - An efficient drug delivery vehicle for botulism countermeasure.
AB  - BACKGROUND: Botulinum neurotoxin (BoNT) is the most potent poison known to
      mankind. Currently no antidote is available to rescue poisoned synapses. An
      effective medical countermeasure strategy would require developing a drug that
      could rescue poisoned neuromuscular synapses and include its efficient delivery
      specifically to poisoned presynaptic nerve terminals. Here we report a drug
      delivery strategy that could directly deliver toxin inhibitors into the
      intoxicated nerve terminal cytosol. RESULTS: A targeted delivery vehicle was
      developed for intracellular transport of emerging botulinum neurotoxin
      antagonists. The drug delivery vehicle consisted of the non-toxic recombinant
      heavy chain of botulinum neurotoxin-A coupled to a 10-kDa amino dextran via the
      heterobifunctional linker 3-(2-pyridylthio)-propionyl hydrazide. The heavy chain
      served to target botulinum neurotoxin-sensitive cells and promote internalization
      of the complex, while the dextran served as a platform to deliver model
      therapeutic molecules to the targeted neurons. Our results indicated that the
      drug delivery vehicle entry into neurons was via BoNT-A receptor mediated
      endocytosis. Once internalized into neurons, the drug carrier component separated
      from the drug delivery vehicle in a fashion similar to the separation of the BoNT
      A light chain from the holotoxin. This drug delivery vehicle could be used to
      deliver BoNT-A antidotes into BoNT-A intoxicated cultured mouse spinal cord
      cells. CONCLUSION: An effective BoNT-based drug delivery vehicle can be used to
      directly deliver toxin inhibitors into intoxicated nerve terminal cytosol. This
      approach can potentially be utilized for targeted drug delivery to treat other
      neuronal and neuromuscular disorders. This report also provides new knowledge of
      endocytosis and exocytosis as well as of BoNT trafficking.

PMID- 19860871
TI  - Characterization of untranslated regions of the salmonid alphavirus 3 (SAV3)
      genome and construction of a SAV3 based replicon.
AB  - Salmonid alphavirus (SAV) causes disease in farmed salmonid fish and is divided
      into different genetic subtypes (SAV1-6). Here we report the cloning and
      characterization of the 5'- and 3'- untranslated regions (UTR) of a SAV3 isolated
      from Atlantic salmon in Norway. The sequences of the UTRs are very similar to
      those of SAV1 and SAV2, but single nucleotide polymorphisms are present, also in
      the 3' - conserved sequence element (3'-CSE). Prediction of the RNA secondary
      structure suggested putative stem-loop structures in both the 5'- and 3'-ends,
      similar to those of alphaviruses from the terrestrial environment, indicating
      that the general genome replication initiation strategy for alphaviruses is also
      utilized by SAV. A DNA replicon vector, pmSAV3, based upon a pVAX1 backbone and
      the SAV3 genome was constructed, and the SAV3 non-structural proteins were used
      to express a reporter gene controlled by the SAV3 subgenomic promoter.
      Transfection of pmSAV3 into CHSE and BF2 cell lines resulted in expression of the
      reporter protein, confirming that the cloned SAV3 replication apparatus and UTRs
      are functional in fish cells.

PMID- 19860872
TI  - Genetic reconstitution of the human adenovirus type 2 temperature-sensitive 1
      mutant defective in endosomal escape.
AB  - Human adenoviruses infect the upper and lower respiratory tracts, the urinary and
      digestive tracts, lymphoid systems and heart, and give rise to epidemic
      conjunctivitis. More than 51 human serotypes have been identified to-date, and
      classified into 6 species A-F. The species C adenoviruses Ad2 and Ad5 (Ad2/5)
      cause upper and lower respiratory disease, but how viral structure relates to the
      selection of particular infectious uptake pathways is not known. An adenovirus
      mutant, Ad2-ts1 had been isolated upon chemical mutagenesis in the past, and
      shown to have unprocessed capsid proteins. Ad2-ts1 fails to package the viral
      protease L3/p23, and Ad2-ts1 virions do not efficiently escape from endosomes. It
      had been suggested that the C22187T point mutation leading to the substitution of
      the conserved proline 137 to leucine (P137L) in the L3/p23 protease was at least
      in part responsible for this phenotype. To clarify if the C22187T mutation is
      necessary and sufficient for the Ad2-ts1 phenotype, we sequenced the genes
      encoding the structural proteins of Ad2-ts1, and confirmed that the Ad2-ts1 DNA
      carries the point mutation C22187T. Introduction of C22187T to the wild-type Ad2
      genome in a bacterial artificial chromosome (Ad2-BAC) gave Ad2-BAC46 virions with
      the full Ad2-ts1 phenotype. Reversion of Ad2-BAC46 gave wild-type Ad2 particles
      indicating that P137L is necessary and sufficient for the Ad2-ts1 phenotype. The
      kinetics of Ad2-ts1 uptake into cells were comparable to Ad2 suggesting similar
      endocytic uptake mechanisms. Surprisingly, infectious Ad2 or Ad5 but not Ad2-ts1
      uptake required CALM (clathrin assembly lymphoid myeloid protein), which controls
      clathrin-mediated endocytosis and membrane transport between endosomes and the
      trans-Golgi-network. The data show that no other mutations than P137L in the
      viral protease are necessary to give rise to particles that are defective in
      capsid processing and endosomal escape. This provides a basis for genetic
      analyses of distinct host requirements for Ad endocytosis and escape from
      endosomes.

PMID- 19860873
TI  - Reporting of euthanasia and physician-assisted suicide in the Netherlands:
      descriptive study.
AB  - BACKGROUND: An important principle underlying the Dutch Euthanasia Act is
      physicians' responsibility to alleviate patients' suffering. The Dutch Act states
      that euthanasia and physician-assisted suicide are not punishable if the
      attending physician acts in accordance with criteria of due care. These criteria
      concern the patient's request, the patient's suffering (unbearable and hopeless),
      the information provided to the patient, the presence of reasonable alternatives,
      consultation of another physician and the applied method of ending life. To
      demonstrate their compliance, the Act requires physicians to report euthanasia to
      a review committee. We studied which arguments Dutch physicians use to
      substantiate their adherence to the criteria and which aspects attract review
      committees' attention. METHODS: We examined 158 files of reported euthanasia and
      physician-assisted suicide cases that were approved by the review committees. We
      studied the physicians' reports and the verdicts of the review committees by
      using a checklist. RESULTS: Physicians reported that the patient's request had
      been well-considered because the patient was clear-headed (65%) and/or had
      repeated the request several times (23%). Unbearable suffering was often
      substantiated with physical symptoms (62%), function loss (33%), dependency (28%)
      or deterioration (15%). In 35%, physicians reported that there had been
      alternatives to relieve patients' suffering which were refused by the majority.
      The nature of the relationship with the consultant was sometimes unclear: the
      consultant was reported to have been an unknown colleague (39%), a known
      colleague (21%), otherwise (25%), or not clearly specified in the report (24%).
      Review committees relatively often scrutinized the consultation (41%) and the
      patient's (unbearable) suffering (32%); they had few questions about possible
      alternatives (1%). CONCLUSION: Dutch physicians substantiate their adherence to
      the criteria in a variable way with an emphasis on physical symptoms. The
      information they provide is in most cases sufficient to enable adequate review.
      Review committees' control seems to focus on (unbearable) suffering and on
      procedural issues.

PMID- 19860875
TI  - High resolution carotid black-blood 3T MR with parallel imaging and dedicated 4
      channel surface coils.
AB  - BACKGROUND: Most of the carotid plaque MR studies have been performed using black
      blood protocols at 1.5 T without parallel imaging techniques. The purpose of this
      study was to evaluate a multi-sequence, black-blood MR protocol using parallel
      imaging and a dedicated 4-channel surface coil for vessel wall imaging of the
      carotid arteries at 3 T. MATERIALS AND METHODS: 14 healthy volunteers and 14
      patients with intimal thickening as proven by duplex ultrasound had their carotid
      arteries imaged at 3 T using a multi-sequence protocol (time-of-flight MR
      angiography, pre-contrast T1w-, PDw- and T2w sequences in the volunteers,
      additional post-contrast T1w- and dynamic contrast enhanced sequences in
      patients). To assess intrascan reproducibility, 10 volunteers were scanned twice
      within 2 weeks. RESULTS: Intrascan reproducibility for quantitative measurements
      of lumen, wall and outer wall areas was excellent with intraclass correlation
      coefficients >0.98 and measurement errors of 1.5%, 4.5% and 1.9%, respectively.
      Patients had larger wall areas than volunteers in both common carotid and
      internal carotid arteries and smaller lumen areas in internal carotid arteries (p
      < 0.001). Positive correlations were found between wall area and cardiovascular
      risk factors such as age, hypertension, coronary heart disease and
      hypercholesterolemia (Spearman's r = 0.45-0.76, p < 0.05). No significant
      correlations were found between wall area and body mass index, gender, diabetes
      or a family history of cardiovascular disease. CONCLUSION: The findings of this
      study indicate that high resolution carotid black-blood 3 T MR with parallel
      imaging is a fast, reproducible and robust method to assess carotid
      atherosclerotic plaque in vivo and this method is ready to be used in clinical
      practice.

PMID- 19860874
TI  - Isolation of Cronobacter spp. (formerly Enterobacter sakazakii) from infant food,
      herbs and environmental samples and the subsequent identification and
      confirmation of the isolates using biochemical, chromogenic assays, PCR and 16S
      rRNA sequencing.
AB  - BACKGROUND: Cronobacter spp. (formerly Enterobacter sakazakii), are a group of
      Gram-negative pathogens that have been implicated as causative agents of
      meningitis and necrotizing enterocolitis in infants. The pathogens are linked to
      infant formula; however, they have also been isolated from a wide range of foods
      and environmental samples. RESULTS: In this study, 233 samples of food, infant
      formula and environment were screened for the presence of Cronobacter spp. in an
      attempt to find its source. Twenty nine strains were isolated from samples of
      spices, herbs, infant foods, and dust obtained from household vacuum cleaners.
      Among the 76 samples of infant food, infant formula, milk powder and non-milk
      dairy products tested, only one sample of infant food contained Cronobacter spp.
      (1.4%). The other Cronobacter spp. isolates recovered include two from household
      vacuum dust, and 26 from 67 samples of herbs and spices. Among the food
      categories analyzed, herbs and spices harbored the highest number of isolates,
      indicating plants as a possible reservoir of this pathogen. Initial screening
      with API 20E test strips yielded 42 presumptive isolates. Further
      characterization using 3 chromogenic media (alpha-MUG, DFI and EsPM) and 8 sets
      of PCR primers detecting ITS (internal transcribed spacer sequences), 16S rRNA,
      zpx, gluA, gluB, OmpA genes followed by nucleotide sequencing of some PCR
      amplicons did not confirm the identity of all the isolates as none of the methods
      proved to be free of both false positives or false negatives. The final
      confirmation step was done by 16S rRNA sequence analysis identifying only 29 of
      the 42 isolates as Cronobacter spp. CONCLUSION: Our studies showed that
      Cronobacter spp. are highly diverse and share many phenotypic traits with other
      Enterobacteriaceae members highlighting the need to use several methods to
      confirm the identity of this pathogen. None of the biochemical, chromogenic or
      PCR primers proved to be a reliable method for confirmation of the identity of
      the isolates as all of them gave either false positives or false negatives or
      both. It is therefore concluded that 16S rRNA sequencing is pivotal to confirm
      the identity of the isolates.

PMID- 19860876
TI  - Towards translation of environmental determinants of physical activity in
      children into multi-sector policy measures: study design of a Dutch project.
AB  - BACKGROUND: Physical inactivity in children is a major health problem in The
      Netherlands as well as in many other Western countries. In addition to health
      promotion among parents and children, creating "active" neighbourhoods can
      contribute to the solution of this health problem. However, changing
      environmental characteristics is often the responsibility of policy sectors
      outside the Public Health domain. Therefore this project identifies and evaluates
      the possibilities of multi-sector policy measures to stimulate physical activity
      in children. METHODS AND DESIGN: The project consists of quantitative as well as
      qualitative research methods and is conducted in four medium sized Dutch cities.
      To identify perceived environmental determinants of physical activity in
      children, a large scale health survey was conducted at 42 primary schools.
      Written questionnaires including topics on the children's physical activity
      behaviour (i.e. sports participation, outdoor play, active commuting, television
      watching and computer usage) and physical and social environmental
      characteristics were completed by 6,601 parents of children aged 3-13 years old
      and 3449 children aged 9-13 years old. In addition, 33 neighbourhood audits
      (systematic observations) were conducted to assess objective neighbourhood
      characteristics. Furthermore, a policy analysis was conducted in the four
      participating municipalities to provide an overview of the current local policy
      measures directed at stimulation of physical activity in children. Policy plans
      of six different policy sectors (Public Health, Sports, Education & Youth,
      Spatial Planning, Traffic & Transport, and Safety) were screened for their
      content on physical activity in children. In addition, semi-structured interviews
      were conducted with policy makers of each of these sectors to identify critical
      success factors in the development and realization of multi-sector policy plans
      aimed at stimulating physical activity in children. The results of all these
      research activities will be discussed with local policy makers during interactive
      workshop sessions in order to identify clear cut multi-sector policy measures
      that stimulate physical activity in children. DISCUSSION: This paper describes
      the study design of a project that focuses on multi-sector policy measures that
      stimulate physical activity in children. Next to extensive research into the
      environmental determinants of physical activity in children, much emphasis is
      placed on the translation of the research outcomes into concrete and feasible
      policy plans.

PMID- 19860877
TI  - Genetic characterization of the complete genome of a highly divergent simian T
      lymphotropic virus (STLV) type 3 from a wild Cercopithecus mona monkey.
AB  - BACKGROUND: The recent discoveries of novel human T-lymphotropic virus type 3
      (HTLV-3) and highly divergent simian T-lymphotropic virus type 3 (STLV-3) subtype
      D viruses from two different monkey species in southern Cameroon suggest that the
      diversity and cross-species transmission of these retroviruses are much greater
      than currently appreciated. RESULTS: We describe here the first full-length
      sequence of a highly divergent STLV-3d(Cmo8699AB) virus obtained by PCR-based
      genome walking using DNA from two dried blood spots (DBS) collected from a wild
      caught Cercopithecus mona monkey. The genome of STLV-3d(Cmo8699AB) is 8913-bp
      long and shares only 77% identity to other PTLV-3s. Phylogenetic analyses using
      Bayesian and maximum likelihood inference clearly show that this highly divergent
      virus forms an independent lineage with high posterior probability and bootstrap
      support within the diversity of PTLV-3. Molecular dating of concatenated gag-pol
      env-tax sequences inferred a divergence date of about 115,117 years ago for STLV
      3d(Cmo8699AB) indicating an ancient origin for this newly identified lineage.
      Major structural, enzymatic, and regulatory gene regions of STLV-3d(Cmo8699AB)
      are intact and suggest viral replication and a predicted pathogenic potential
      comparable to other PTLV-3s. CONCLUSION: When taken together, the inferred
      ancient origin of STLV-3d(Cmo8699AB), the presence of this highly divergent virus
      in two primate species from the same geographical region, and the ease with which
      STLVs can be transmitted across species boundaries all suggest that STLV-3d may
      be more prevalent and widespread. Given the high human exposure to nonhuman
      primates in this region and the unknown pathogenicity of this divergent PTLV-3,
      increased surveillance and expanded prevention activities are necessary. Our
      ability to obtain the complete viral genome from DBS also highlights further the
      utility of this method for molecular-based epidemiologic studies.

PMID- 19860878
TI  - The measurement of reactive oxygen species in human neat semen and in suspended
      spermatozoa: a comparison.
AB  - BACKGROUND: It is generally accepted that oxidative stress is an important factor
      in male infertility because it may impair the physiological function of
      spermatozoa at the molecular level. Nevertheless, although several approaches
      have been reported, the imbalance between production of reactive oxygen species
      (ROS) and activity of the antioxidant defense system in semen is difficult to
      investigate and remains poorly understood. METHODS: This study compares
      measurement of ROS production in neat semen and in washed spermatozoa obtained
      from the same ejaculate, and suspended in phosphate buffered saline using exactly
      the same luminol-mediated chemiluminescence method. Ninety one samples were
      obtained from males of infertile couples and 34 from volunteers with proven
      fertility. RESULTS: As expected, ROS levels were markedly lower in neat semen
      than in washed spermatozoa suspensions where seminal plasma with its potent
      antioxidant capacity was removed. In the cases of both neat semen and washed
      spermatozoa, ROS production was lowest in samples from normozoospermic males and
      highest in samples containing more than half million peroxidase-positive
      leukocytes per milliliter. For all samples, there was a significant positive
      correlation between ROS production by neat semen and that by washed spermatozoa
      suspension. CONCLUSION: Measurement of ROS production in neat semen better
      reflects actual oxidative status because it detects only the overproduction of
      ROS which are not effectively scavenged by antioxidant capacity of seminal fluid.
      The results of our study show a good commutability of both measurements for
      identification of semen samples with high ROS production. The measurement in neat
      semen is even less time consuming and therefore easier to implement into
      laboratory routine.

PMID- 19860879
TI  - Backstep scanning ion conductance microscopy as a tool for long term
      investigation of single living cells.
AB  - Scanning ion conductance microscopy (SICM) is a suitable tool for imaging
      surfaces of living cells in a contact-free manner. We have shown previously that
      SICM in backstep mode allows one to trace the outlines of entire cell somata and
      to detect changes in cellular shape and volume. Here we report that SICM can be
      employed to quantitatively observe cellular structures such as cell processes of
      living cells as well as cell somata of motile cells in the range of hours.

PMID- 19860880
TI  - LMP1-augmented kappa intron enhancer activity contributes to upregulation
      expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in
      nasopharyngeal carcinoma cells.
AB  - BACKGROUND: Expression of kappa gene is under the control of distinct cis
      regulatory elements, including the kappa intron enhancer (iE kappa) and the kappa
      3' enhancer (3'E kappa). The active enhancers and expression of immunoglobulin is
      generally considered to be restricted to B lymphocytes. However, accumulating
      evidence indicated that epithelial cancer cells, including nasopharyngeal
      carcinoma (NPC) cell lines, express immunoglobulins. The mechanisms underlying
      the expression of Igs in nonlymphoid cells remain unknown. On the basis of our
      previous finding that expression of kappa light chain in NPC cells can be
      upregulated by EBV-encoded latent membrane protein 1(LMP1) through the activation
      of NF-kappaB and AP-1 signaling pathways, we thus use NPC cells as model to
      further explore the molecular mechanisms of nonlymphoid cells expressing Ig
      kappa. RESULTS: In this study, luciferase reporter plasmid containing human wild
      type iE kappa, and its derivative plasmids containing mutant binding sites for
      transcription factor NF-kappaB or AP-1 were constructed. Luciferase reporter
      assays demonstrate iE kappa is active in Ig kappa-expressing NPC cells and LMP1
      expression can upregulate the activity of iE kappa in NPC cells. Mutation of the
      NF-kappaB or AP-1 site within and downstream the iE kappa, inhibition of the NF
      kappaB and AP-1 pathways by their respective chemical inhibitor Bay11-7082 and
      SP600125 as well as stable or transient expression of dominant-negative mutant of
      I kappaB alpha (DNMI kappaB alpha) or of c-Jun (TAM67) indicate that both sites
      are functional and LMP1-enhanced iE kappa activity is partly regulated by these
      two sites. Gel shift assays show that LMP1 promotes NF-kappaB subunits p52 and
      p65 as well as AP-1 family members c-Jun and c-Fos binding to the kappa NF-kappaB
      and the kappa AP-1 motifs in vitro, respectively. Both chemical inhibitors and
      dominant negative mutants targeting for NF-kappaB and AP-1 pathways can attenuate
      the LMP1-enhanced bindings. Co-IP assays using nuclear extracts from HNE2-LMP1
      cells reveal that p52 and p65, c-Jun and c-Fos proteins interact with each other
      at endogenous levels. ChIP assays further demonstrate p52 and p65 binding to the
      kappaB motif as well as c-Jun and c-Fos binding to the AP-1 motif of Ig kappa
      gene in vivo. CONCLUSION: These results suggest that human iE kappa is active in
      Ig kappa-expressing NPC cells and LMP1-stimulated NF-kappaB and AP-1 activation
      results in an augmenting activation of the iE kappa. LMP1 promotes the
      interactions of heterodimeric NF-kappaB (p52/p65) and heterodimeric AP-1 (c-Jun/c
      Fos) transcription factors with the human iE kappa enhancer region are important
      for the upregulation of kappa light chain in LMP1-positive nasopharyngeal
      carcinoma cells.

PMID- 19860881
TI  - Tetrapisispora phaffii killer toxin is a highly specific beta-glucanase that
      disrupts the integrity of the yeast cell wall.
AB  - BACKGROUND: Killer yeasts have been used to combat contaminating wild yeasts in
      food, to control pathogenic fungi in plants, and in the medical field, to develop
      novel antimycotics for the treatment of human and animal fungal infections. Among
      these killer yeasts, Tetrapisispora phaffii (formerly known as Kluyveromyces
      phaffii) secretes a glycoprotein known as Kpkt that is lethal to spoilage yeasts
      under winemaking conditions. In the present study, the mode of action of Kpkt,
      and the specific damage produced by this toxin on sensitive yeasts is
      investigated. RESULTS: The use of castanospermine, a beta-glucanase inhibitor,
      demonstrated that beta-glucanase activity is essential for the Kpkt killer
      activity in vivo. Accordingly, Kpkt has no killer activity on either sensitive
      yeast spheroplasts or whole sensitive cells in the presence of isosmothic medium
      (0.8 molar sorbitol). Kpkt induces ultrastructural modifications in the cell wall
      of sensitive strains, as shown by confocal microscopy, laser-scanning electron
      microscopy, and atomic force microscopy. The Kpkt killer action is mediated by
      the glucidic portion of the toxin. This, in turn, appears to be involved both in
      the stronger cytocidal activity and in the selectivity for the sensitive strain
      shown by Kpkt compared to laminarinase. CONCLUSION: Collectively, these data
      indicate that the mode of action of Kpkt is directed towards the disruption of
      cell-wall integrity, and that this is mediated by a highly specific beta
      glucanase activity. In this, Kpkt differs from other microbial beta-glucanases
      that do not show killer activities.

PMID- 19860882
TI  - Developing a set of ancestry-sensitive DNA markers reflecting continental origins
      of humans.
AB  - BACKGROUND: The identification and use of Ancestry-Sensitive Markers (ASMs), i.e.
      genetic polymorphisms facilitating the genetic reconstruction of geographical
      origins of individuals, is far from straightforward. RESULTS: Here we describe
      the ascertainment and application of five different sets of 47 single nucleotide
      polymorphisms (SNPs) allowing the inference of major human groups of different
      continental origin. For this, we first used 74 cell lines, representing human
      males from six different geographical areas and screened them with the Affymetrix
      Mapping 10K assay. In addition to using summary statistics estimating the genetic
      diversity among multiple groups of individuals defined by geography or language,
      we also used the program STRUCTURE to detect genetically distinct subgroups.
      Subsequently, we used a pairwise F(ST) ranking procedure among all pairs of
      genetic subgroups in order to identify a single best performing set of ASMs. Our
      initial results were independently confirmed by genotyping this set of ASMs in 22
      individuals from Somalia, Afghanistan and Sudan and in 919 samples from the CEPH
      Human Genome Diversity Panel (HGDP-CEPH) CONCLUSION: By means of our pairwise
      population F(ST) ranking approach we identified a set of 47 SNPs that could serve
      as a panel of ASMs at a continental level.

PMID- 19860883
TI  - Randomised controlled trial of local corticosteroid injections for de Quervain's
      tenosynovitis in general practice.
AB  - BACKGROUND: De Quervain's tenosynovitis is a stenosing tenosynovitis of the first
      dorsal compartment of the wrist and leads to wrist pain and to impaired function
      of the wrist and hand. It can be treated by splinting, local corticosteroid
      injection and operation. In this study effectiveness of local corticosteroid
      injections for de Quervain's tenosynovitis provided by general practitioners was
      assessed. METHODS: Participants with de Quervain's tenosynovitis were recruited
      by general practitioners. Short-term outcomes (one week after injections) were
      assessed in a randomised, placebo-controlled trial. Long-term effectiveness was
      evaluated in an open prospective cohort-study of steroid responders during a
      follow-up period of 12 months. Participants were randomised to one or two local
      injections of 1 ml of triamcinolonacetonide (TCA) or 1 ml of NaCl 0.9% (placebo).
      Non-responders to NaCl were treated with additional TCA injections. Main outcomes
      were immediate treatment response, severity of pain, improvement as perceived by
      participant and functional disability using sub items hand and finger function of
      the Dutch Arthritis Impact Measurement Scale (Dutch AIMS-2-HFF). RESULTS: 11
      general practitioners included 21 wrists in 21 patients. The TCA-group had better
      results for short-term outcomes treatment response (78% vs. 25%; p = 0.015),
      perceived improvement (78% vs. 33%; p = 0.047) and severity of pain (4.27 vs.
      1.33; p = 0.031) but not for the Dutch-AIMS-HFF (2.71 vs. 1.92; p = 0.112).
      Absolute risk reduction for the main outcome short-term treatment response was
      0.55 (95% CI: 0.34, 0.76) with a number needed to treat of 2 (95% CI: 1, 3). In
      the cohort of steroid responders (n = 12) the beneficial effects of steroid
      injections were sustained during the follow-up of 12 months regarding severity of
      pain (p = 0.67) and scores of Dutch AIMS-2-HFF (p = 0.36), but not for patient
      perceived improvement (p = 0.02). No adverse events were observed during the 12
      months of follow-up. CONCLUSION: One or two local injections of 1 ml
      triamcinolonacetonide 10 mg/ml provided by general practitioners leads to
      improvement in the short term in participants with de Quervain's tenosynovitis
      when compared to placebo. The short-term beneficial effects of steroid injections
      for symptoms were maintained during the follow-up after 12 months. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN53171398.

PMID- 19860884
TI  - Stratification of co-evolving genomic groups using ranked phylogenetic profiles.
AB  - BACKGROUND: Previous methods of detecting the taxonomic origins of arbitrary
      sequence collections, with a significant impact to genome analysis and in
      particular metagenomics, have primarily focused on compositional features of
      genomes. The evolutionary patterns of phylogenetic distribution of genes or
      proteins, represented by phylogenetic profiles, provide an alternative approach
      for the detection of taxonomic origins, but typically suffer from low accuracy.
      Herein, we present rank-BLAST, a novel approach for the assignment of protein
      sequences into genomic groups of the same taxonomic origin, based on the ranking
      order of phylogenetic profiles of target genes or proteins across the reference
      database. RESULTS: The rank-BLAST approach is validated by computing the
      phylogenetic profiles of all sequences for five distinct microbial species of
      varying degrees of phylogenetic proximity, against a reference database of 243
      fully sequenced genomes. The approach - a combination of sequence searches,
      statistical estimation and clustering - analyses the degree of sequence
      divergence between sets of protein sequences and allows the classification of
      protein sequences according to the species of origin with high accuracy, allowing
      taxonomic classification of 64% of the proteins studied. In most cases, a main
      cluster is detected, representing the corresponding species. Secondary,
      functionally distinct and species-specific clusters exhibit different patterns of
      phylogenetic distribution, thus flagging gene groups of interest. Detailed
      analyses of such cases are provided as examples. CONCLUSION: Our results indicate
      that the rank-BLAST approach can capture the taxonomic origins of sequence
      collections in an accurate and efficient manner. The approach can be useful both
      for the analysis of genome evolution and the detection of species groups in
      metagenomics samples.

PMID- 19860885
TI  - Genomic taxonomy of Vibrios.
AB  - BACKGROUND: Vibrio taxonomy has been based on a polyphasic approach. In this
      study, we retrieve useful taxonomic information (i.e. data that can be used to
      distinguish different taxonomic levels, such as species and genera) from 32
      genome sequences of different vibrio species. We use a variety of tools to
      explore the taxonomic relationship between the sequenced genomes, including
      Multilocus Sequence Analysis (MLSA), supertrees, Average Amino Acid Identity
      (AAI), genomic signatures, and Genome BLAST atlases. Our aim is to analyse the
      usefulness of these tools for species identification in vibrios. RESULTS: We have
      generated four new genome sequences of three Vibrio species, i.e., V.
      alginolyticus 40B, V. harveyi-like 1DA3, and V. mimicus strains VM573 and VM603,
      and present a broad analyses of these genomes along with other sequenced Vibrio
      species. The genome atlas and pangenome plots provide a tantalizing image of the
      genomic differences that occur between closely related sister species, e.g. V.
      cholerae and V. mimicus. The vibrio pangenome contains around 26504 genes. The V.
      cholerae core genome and pangenome consist of 1520 and 6923 genes, respectively.
      Pangenomes might allow different strains of V. cholerae to occupy different
      niches. MLSA and supertree analyses resulted in a similar phylogenetic picture,
      with a clear distinction of four groups (Vibrio core group, V. cholerae-V.
      mimicus, Aliivibrio spp., and Photobacterium spp.). A Vibrio species is defined
      as a group of strains that share > 95% DNA identity in MLSA and supertree
      analysis, > 96% AAI, < or = 10 genome signature dissimilarity, and > 61% proteome
      identity. Strains of the same species and species of the same genus will form
      monophyletic groups on the basis of MLSA and supertree. CONCLUSION: The
      combination of different analytical and bioinformatics tools will enable the most
      accurate species identification through genomic computational analysis. This
      endeavour will culminate in the birth of the online genomic taxonomy whereby
      researchers and end-users of taxonomy will be able to identify their isolates
      through a web-based server. This novel approach to microbial systematics will
      result in a tremendous advance concerning biodiversity discovery, description,
      and understanding.

PMID- 19860886
TI  - Mercury exposure, nutritional deficiencies and metabolic disruptions may affect
      learning in children.
AB  - Among dietary factors, learning and behavior are influenced not only by
      nutrients, but also by exposure to toxic food contaminants such as mercury that
      can disrupt metabolic processes and alter neuronal plasticity. Neurons lacking in
      plasticity are a factor in neurodevelopmental disorders such as autism and mental
      retardation. Essential nutrients help maintain normal neuronal plasticity.
      Nutritional deficiencies, including deficiencies in the long chain
      polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the
      amino acid methionine, and the trace minerals zinc and selenium, have been shown
      to influence neuronal function and produce defects in neuronal plasticity, as
      well as impact behavior in children with attention deficit hyperactivity
      disorder. Nutritional deficiencies and mercury exposure have been shown to alter
      neuronal function and increase oxidative stress among children with autism. These
      dietary factors may be directly related to the development of behavior disorders
      and learning disabilities. Mercury, either individually or in concert with other
      factors, may be harmful if ingested in above average amounts or by sensitive
      individuals. High fructose corn syrup has been shown to contain trace amounts of
      mercury as a result of some manufacturing processes, and its consumption can also
      lead to zinc loss. Consumption of certain artificial food color additives has
      also been shown to lead to zinc deficiency. Dietary zinc is essential for
      maintaining the metabolic processes required for mercury elimination. Since high
      fructose corn syrup and artificial food color additives are common ingredients in
      many foodstuffs, their consumption should be considered in those individuals with
      nutritional deficits such as zinc deficiency or who are allergic or sensitive to
      the effects of mercury or unable to effectively metabolize and eliminate it from
      the body.

PMID- 19860887
TI  - The BSA-induced Ca2+ influx during sperm capacitation is CATSPER channel
      dependent.
AB  - BACKGROUND: Serum albumin is a key component in mammalian sperm capacitation, a
      functional maturation process by which sperm become competent to fertilize
      oocytes. Capacitation is accompanied by several cellular and molecular changes
      including an increased tyrosine phosphorylation of sperm proteins and a
      development of hyperactivated sperm motility. Both of these processes require
      extracellular calcium, but how calcium enters sperm during capacitation is not
      well understood. METHODS: BSA-induced changes in intracellular calcium
      concentration were studied using Fluo-4 and Fura-2 calcium imaging with wild-type
      and Catsper1 knockout mouse sperm. RESULTS: We found that the fast phase of the
      BSA-induced rises in intracellular calcium concentration was absent in the
      Catsper1 knockout sperm and could be restored by an EGFP-CATSPER1 fusion protein.
      The calcium concentration increases were independent of G-proteins and
      phospholipase C but could be partially inhibited when intracellular pH was
      clamped. The changes started in the principal piece and propagated toward the
      sperm head. CONCLUSION: We conclude that the initial phase of the increases in
      intracellular calcium concentration induced by BSA requires the CATSPER channel,
      but not the voltage-gated calcium channel. Our findings identify the molecular
      conduit responsible for the calcium entry required for the sperm motility changes
      that occur during capacitation.

PMID- 19860888
TI  - Microbicides Development Programme: design of a phase III trial to measure the
      efficacy of the vaginal microbicide PRO 2000/5 for HIV prevention.
AB  - BACKGROUND: With 2.5 million new HIV infections per year, effective preventive
      methods against HIV are urgently needed, especially in sub-Saharan Africa. MDP301
      is an ongoing trial of the vaginal microbicide PRO 2000/5 being conducted by the
      Microbicides Development Programme. The main objective of the trial is to
      determine the efficacy and safety of 0.5% and 2% concentrations of PRO 2000/5 gel
      compared to placebo in preventing vaginally acquired HIV infection.
      METHODS/DESIGN: MDP301 is a multicentre randomised placebo-controlled Phase III
      trial. The design was informed by pre-trial feasibility and pilot studies. The
      choice of trial population, assessments and endpoints are discussed along with
      statistical and ethical considerations. Adaptations to the design were made
      during the conduct of the trial; these included closing a study arm and changing
      the timing of the primary endpoint. DISCUSSION: The development of effective
      microbicide products remains one of the strongest hopes for new biomedical
      prevention tools. MDP301 is the largest Phase III microbicide trial to date, with
      9404 enrolments, and is scheduled for completion in September 2009. Results are
      expected towards the end of 2009.

PMID- 19860889
TI  - The role and molecular mechanism of D-aspartic acid in the release and synthesis
      of LH and testosterone in humans and rats.
AB  - BACKGROUND: D-aspartic acid is an amino acid present in neuroendocrine tissues of
      invertebrates and vertebrates, including rats and humans. Here we investigated
      the effect of this amino acid on the release of LH and testosterone in the serum
      of humans and rats. Furthermore, we investigated the role of D-aspartate in the
      synthesis of LH and testosterone in the pituitary and testes of rats, and the
      molecular mechanisms by which this amino acid triggers its action. METHODS: For
      humans: A group of 23 men were given a daily dose of D-aspartate (DADAVIT) for 12
      days, whereas another group of 20 men were given a placebo. For rats: A group of
      10 rats drank a solution of either 20 mM D-aspartate or a placebo for 12 days.
      Then LH and testosterone accumulation was determined in the serum and D-aspartate
      accumulation in tissues. The effects of D-aspartate on the synthesis of LH and
      testosterone were gauged on isolated rat pituitary and Leydig cells. Tissues were
      incubated with D-aspartate, and then the concentration (synthesis) of LH and cGMP
      in the pituitary and of testosterone and cAMP in the Leydig cells was determined.
      RESULTS: In humans and rats, sodium D-aspartate induces an enhancement of LH and
      testosterone release. In the rat pituitary, sodium D-aspartate increases the
      release and synthesis of LH through the involvement of cGMP as a second
      messenger, whereas in rat testis Leydig cells, it increases the synthesis and
      release of testosterone and cAMP is implicated as second messenger. In the
      pituitary and in testes D-Asp is synthesized by a D-aspartate racemase which
      convert L-Asp into D-Asp. The pituitary and testes possesses a high capacity to
      trapping circulating D-Asp from hexogen or endogen sources. CONCLUSION: D
      aspartic acid is a physiological amino acid occurring principally in the
      pituitary gland and testes and has a role in the regulation of the release and
      synthesis of LH and testosterone in humans and rats.

PMID- 19860890
TI  - Risk factors for chronic kidney disease in Japan: a community-based study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is increasingly being recognized as a
      predictor for both end-stage renal disease and cardiovascular disease. The
      present study, conducted on individuals from a community in Arita, Japan, was
      designed to evaluate biomarkers that can be used to determine the associated
      factors for CKD. METHODS: This study involved 1554 individuals. Kidney function
      was evaluated in terms of the creatinine-based estimated glomerular filtration
      rate (eGFR), which was determined using the Modification of Diet in Renal Disease
      equation. Low eGFR was defined as eGFR < 60 mL/min per 1.73 m2. The concentration
      of both urinary albumin and urinary type IV collagen were measured. RESULTS: In
      the younger participants (age, <65 years), the odds ratio (95% confidence
      interval [CI]) of low eGFR was 1.17 (1.02 to 1.34) for each 1 year older age,
      6.28 (1.41 to 28.03) for urinary albumin creatinine ratio (ACR) over 17.9 mg/g
      and 9.43 (2.55 to 34.91) for hyperlipidemia. On the other hand, among the elderly
      participants (age, > or = 65 years), the odds ratio (95% CI) of low eGFR was 2.97
      (1.33 to 6.62) for gender, 1.62 (1.06 to 2.50) for hypertension and 1.97 (1.19 to
      3.28) for hyperlipidemia. Urinary type IV collagen creatinine ratio was not
      identified as an associated factor for low eGFR. CONCLUSION: In this present
      cross-sectional community-based study, ACR is associated with CKD, which was
      defined as an eGFR of less than 60 mL/min per 1.73 m2, in the younger
      participants but not in the older participants.

PMID- 19860891
TI  - Estimating the phylogeny and divergence times of primates using a supermatrix
      approach.
AB  - BACKGROUND: The primates are among the most broadly studied mammalian orders,
      with the published literature containing extensive analyses of their behavior,
      physiology, genetics and ecology. The importance of this group in medical and
      biological research is well appreciated, and explains the numerous molecular
      phylogenies that have been proposed for most primate families and genera.
      Composite estimates for the entire order have been infrequently attempted, with
      the last phylogenetic reconstruction spanning the full range of primate
      evolutionary relationships having been conducted over a decade ago. RESULTS: To
      estimate the structure and tempo of primate evolutionary history, we employed
      Bayesian phylogenetic methods to analyze data supermatrices comprising 7
      mitochondrial genes (6,138 nucleotides) from 219 species across 67 genera and 3
      nuclear genes (2,157 nucleotides) from 26 genera. Many taxa were only partially
      represented, with an average of 3.95 and 5.43 mitochondrial genes per species and
      per genus, respectively, and 2.23 nuclear genes per genus. Our analyses of
      mitochondrial DNA place Tarsiiformes as the sister group of Strepsirrhini. Within
      Haplorrhini, we find support for the primary divergence of Pitheciidae in
      Platyrrhini, and our results suggest a sister grouping of African and non-African
      colobines within Colobinae and of Cercopithecini and Papionini within
      Cercopthecinae. Date estimates for nodes within each family and genus are
      presented, with estimates for key splits including: Strepsirrhini-Haplorrhini 64
      million years ago (MYA), Lemuriformes-Lorisiformes 52 MYA, Platyrrhini-Catarrhini
      43 MYA and Cercopithecoidea-Hominoidea 29 MYA. CONCLUSION: We present an up-to
      date, comprehensive estimate of the structure and tempo of primate evolutionary
      history. Although considerable gaps remain in our knowledge of the primate
      phylogeny, increased data sampling, particularly from nuclear loci, will be able
      to provide further resolution.

PMID- 19860892
TI  - The interaction of hepatitis A virus (HAV) with soluble forms of its cellular
      receptor 1 (HAVCR1) share the physiological requirements of infectivity in cell
      culture.
AB  - BACKGROUND: Hepatitis A virus (HAV), an atypical Picornaviridae that causes acute
      hepatitis in humans, usurps the HAV cellular receptor 1 (HAVCR1) to infect cells.
      HAVCR1 is a class 1 integral membrane glycoprotein that contains two
      extracellular domains: a virus-binding immunoglobulin-like (IgV) domain and a
      mucin-like domain that extends the IgV from the cell membrane. Soluble forms of
      HAVCR1 bind, alter, and neutralize cell culture-adapted HAV, which is attenuated
      for humans. However, the requirements of the HAV-HAVCR1 interaction have not been
      fully characterized, and it has not been determined whether HAVCR1 also serves as
      a receptor for wild-type (wt) HAV. Here, we used HAV soluble receptor
      neutralization and alteration assays to study the requirements of the HAV-HAVCR1
      interaction and to determine whether HAVCR1 is also a receptor for wt HAV.
      RESULTS: Treatment of HAV with a soluble form of HAVCR1 that contained the IgV
      and two-thirds of the mucin domain fused to the Fc fragment of human IgG1 (D1 muc
      Fc), altered particles at 37 degrees C but left a residual level of unaltered
      particles at 4 degrees C. The kinetics of neutralization of HAV by D1 muc-Fc was
      faster at 37 degrees C than at 4 degrees C. Alteration of HAV particles by D1 muc
      Fc required Ca, which could not be replaced by Li, Na, Mg, Mn, or Zn.
      Neutralization of HAV by D1 muc-Fc occurred at pH 5 to 8 but was more efficient
      at pH 6 to 7. D1 muc-Fc neutralized wt HAV as determined by a cell culture system
      that allows the growth of wt HAV. CONCLUSION: The interaction of HAV with soluble
      forms of HAVCR1 shares the temperature, Ca, and pH requirements for infectivity
      in cell culture and therefore mimics the cell entry process of HAV. Since soluble
      forms of HAVCR1 also neutralized wt HAV, this receptor may play a significant
      role in pathogenesis of HAV.

PMID- 19860893
TI  - Spatio-temporal expression patterns of anandamide-binding receptors in rat
      implantation sites: evidence for a role of the endocannabinoid system during the
      period of placental development.
AB  - BACKGROUND: Although there is growing evidence that endocannabinoids play a
      critical role in early pregnancy, there are no studies describing the possible
      targets for this system after implantation. The endometrial stroma, which
      undergoes extensive proliferation and differentiation giving rise to the decidua
      and the trophoblast cells that invade after the initial stages of implantation,
      are potential targets. Since high anandamide (AEA) levels, the main
      endocannabinoid, are detrimental to implantation and in order to gain insight
      into the role of the endocannabinoid system in the development of the
      fetoplacental unit, the spatio-temporal pattern of expression of the anandamide
      binding receptors, CB1, CB2 and the vanilloid receptor (TRPV1), were investigated
      by quantitative RT-PCR, western blot and immunohistochemistry. METHODS: Rat
      uterine maternal tissues from different days of pregnancy were used to
      investigate the expression of CB1, CB2 and vanilloid receptors by quantitative RT
      PCR, western blot and immunohistochemistry. RESULTS: The data indicate that all
      the three receptors were expressed in decidualized cells and placenta.
      Interestingly, CB1 and CB2 were also expressed in smooth muscle cells of maternal
      blood vessels and in endovascular trophoblast cells, whereas TRPV1 was mainly
      expressed in uterine natural killer (uNK) cells and in the longitudinal muscle
      layer throughout pregnancy. In all tissues, CB2 protein was present at a lower
      level than CB1. CONCLUSION: These observations support a role for the
      endocannabinoid system during the period of decidualization and placental
      development.

PMID- 19860894
TI  - Plasma and urine biomarkers in acute viral hepatitis E.
AB  - BACKGROUND: Hepatitis E, caused by the hepatitis E virus (HEV), is endemic to
      developing countries where it manifests as waterborne outbreaks and sporadic
      cases. Though generally self-limited with a low mortality rate, some cases
      progress to fulminant hepatic failure (FHF) with high mortality. With no
      identified predictive or diagnostic markers, the events leading to disease
      exacerbation are not known. Our aim is to use proteomic tools to identify
      biomarkers of acute and fulminant hepatitis E. RESULTS: We analyzed proteins in
      the plasma and urine of hepatitis E patients and healthy controls by two
      dimensional Differential Imaging Gel Electrophoresis (DIGE) and mass
      spectrometry, and identified over 30 proteins to be differentially expressed
      during acute hepatitis E. The levels of one plasma protein, transthyretin, and
      one urine protein, alpha-1-microglobulin (alpha1m), were then quantitated by
      enzyme immunoassay (EIA) in clinical samples from a larger group of patients and
      controls. The results showed decreased plasma transthyretin levels (p < 0.005)
      and increased urine alpha1m levels (p < 0.001) in acute hepatitis E patients,
      compared to healthy controls. Preliminary results also showed lower urine zinc
      alpha glycoprotein levels in fulminant hepatitis E compared to acute disease;
      this remains to be confirmed with more fulminant cases. CONCLUSION: Our results
      demonstrate the utility of characterizing plasma and urine proteomes for
      signatures of the host response to HEV infection. We predict that plasma
      transthyretin and urine alpha1m could be reliable biomarkers of acute hepatitis
      E. Besides the utility of this approach to biomarker discovery, proteome-level
      changes in human biofluids would also guide towards a better understanding of
      host-virus interaction and disease.

PMID- 19860895
TI  - Novel deployment of a covered duodenal stent in open surgery to facilitate
      closure of a malignant duodenal perforation.
AB  - BACKGROUND: Its a dilemma to attempt a palliative procedure to debulk the tumour
      and/or prevent future obstructive complications in a locally advanced intra
      abdominal malignancy. CASE PRESENTATION: A 38 year old Vietnamese man presented
      with a carcinoma of the colon which had invaded the gallbladder and duodenum with
      a sealed perforation of the second part of the duodenum. Following surgical
      exploration, it was evident that primary closure of the perforated duodenum was
      not possible due to the presence of unresectable residual tumour. CONCLUSION: We
      describe a novel technique using a covered duodenal stent deployed at open
      surgery to aid closure of a malignant duodenal perforation.

PMID- 19860896
TI  - A BAC-based physical map of Brachypodium distachyon and its comparative analysis
      with rice and wheat.
AB  - BACKGROUND: Brachypodium distachyon (Brachypodium) has been recognized as a new
      model species for comparative and functional genomics of cereal and bioenergy
      crops because it possesses many biological attributes desirable in a model, such
      as a small genome size, short stature, self-pollinating habit, and short
      generation cycle. To maximize the utility of Brachypodium as a model for basic
      and applied research it is necessary to develop genomic resources for it. A BAC
      based physical map is one of them. A physical map will facilitate analysis of
      genome structure, comparative genomics, and assembly of the entire genome
      sequence. RESULTS: A total of 67,151 Brachypodium BAC clones were fingerprinted
      with the SNaPshot HICF fingerprinting method and a genome-wide physical map of
      the Brachypodium genome was constructed. The map consisted of 671 contigs and
      2,161 clones remained as singletons. The contigs and singletons spanned 414 Mb. A
      total of 13,970 gene-related sequences were detected in the BAC end sequences
      (BES). These gene tags aligned 345 contigs with 336 Mb of rice genome sequence,
      showing that Brachypodium and rice genomes are generally highly colinear.
      Divergent regions were mainly in the rice centromeric regions. A dot-plot of
      Brachypodium contigs against the rice genome sequences revealed remnants of the
      whole-genome duplication caused by paleotetraploidy, which were previously found
      in rice and sorghum. Brachypodium contigs were anchored to the wheat deletion bin
      maps with the BES gene-tags, opening the door to Brachypodium-Triticeae
      comparative genomics. CONCLUSION: The construction of the Brachypodium physical
      map, and its comparison with the rice genome sequence demonstrated the utility of
      the SNaPshot-HICF method in the construction of BAC-based physical maps. The map
      represents an important genomic resource for the completion of Brachypodium
      genome sequence and grass comparative genomics. A draft of the physical map and
      its comparisons with rice and wheat are available at
      http://phymap.ucdavis.edu/brachypodium/.

PMID- 19860897
TI  - Role of L2 cysteines in papillomavirus infection and neutralization.
AB  - Vaccination of mice with minor capsid protein L2 or passive transfer with the L2
      specific neutralizing monoclonal antibody RG-1 protects against human
      papillomavirus type 16 (HPV16) challenge. Here we explored the nature of the RG-1
      epitope and its contribution to viral infectivity. RG-1 bound equivalently HPV16
      L2 residues 17-36 with or without an intact C22-C28 disulphide bridge. HPV16 L2
      mutations K20A, C22A, C22S, C28A, C28S, or P29A prevented RG-1 binding, whereas
      Y19A, K23A or Q24A had no impact. Mutation of either C22 or C28 to alanine or
      serine compromises HPV16 pseudoviral infectivity both in vitro and in the murine
      vaginal tract, but does not impact pseudovirion assembly. Despite their lack of
      infectivity, HPV16 pseudovirions containing C22S or C28S mutant L2 bind to cell
      surfaces, are taken up, and expose the 17-36 region on the virion surface as for
      wild type HPV16 pseudovirions suggesting normal furin cleavage of L2. Mutation of
      the second cysteine residue in Bovine papillomavirus type 1 (BPV1) L2 to serine
      (C25S) dramatically reduced the infectivity of BPV1 pseudovirions. Surprisingly,
      in contrast to the double mutation in HPV16 L2, the BPV1 L2 C19S, C25S double
      mutation reduced BPV1 pseudovirion infectivity of 293TT cells by only half.

PMID- 19860898
TI  - Evaluation of the bacterial diversity among and within individual venous leg
      ulcers using bacterial tag-encoded FLX and titanium amplicon pyrosequencing and
      metagenomic approaches.
AB  - BACKGROUND: Approximately 1 out of every 100 individuals has some form of venous
      insufficiency, which can lead to chronic venous disease and Venous Leg Ulcer
      (VLU). There are known underlying pathologies which contribute to the chronic
      nature of VLU including biofilm phenotype infections. RESULTS: Using
      pyrosequencing based approaches we evaluated VLU to characterize their microbial
      ecology. Results show that VLU infections are polymicrobial with no single
      bacterium colonizing the wounds. The most ubiquitous and predominant organisms
      include a previously uncharacterized bacteroidales, various anaerobes,
      Staphylococcus, Corynebacterium, and Serratia. Topological analysis of VLU show
      some notable differences in bacterial populations across the surface of the
      wounds highlighting the importance of sampling techniques during diagnostics.
      Metagenomics provide a preliminary indication that there may be protozoa, fungi
      and possibly an undescribed virus associated with these wounds. CONCLUSION: The
      polymicrobial nature of VLU and previous research on diabetic foot ulcers and
      surgical site infections suggest that the future of therapy for such wounds lies
      in the core of the logical and proven multiple concurrent strategy approach,
      which has been termed "biofilm-based wound care" and the use of individualized
      therapeutics rather than in a single treatment modality.

PMID- 19860899
TI  - A functional analysis of the CREB signaling pathway using HaloCHIP-chip and high
      throughput reporter assays.
AB  - BACKGROUND: Regulation of gene expression is essential for normal development and
      cellular growth. Transcriptional events are tightly controlled both spatially and
      temporally by specific DNA-protein interactions. In this study we finely map the
      genome-wide targets of the CREB protein across all known and predicted human
      promoters, and characterize the functional consequences of a subset of these
      binding events using high-throughput reporter assays. To measure CREB binding, we
      used HaloCHIP, an antibody-free alternative to the ChIP method that utilizes the
      HaloTag fusion protein, and also high-throughput promoter-luciferase reporter
      assays, which provide rapid and quantitative screening of promoters for
      transcriptional activation or repression in living cells. RESULTS: In analysis of
      CREB genome-wide binding events using a comprehensive DNA microarray of human
      promoters, we observe for the first time that CREB has a strong preference for
      binding at bidirectional promoters and unlike unidirectional promoters, these
      binding events often occur downstream of transcription start sites. Comparison
      between HaloCHIP-chip and ChIP-chip data reveal this to be true for both
      methodologies, indicating it is not a bias of the technology chosen.
      Transcriptional data obtained from promoter-luciferase reporter arrays also show
      an unprecedented, high level of activation of CREB-bound promoters in the
      presence of the co-activator protein TORC1. CONCLUSION: These data suggest for
      the first time that TORC1 provides directional information when CREB is bound at
      bidirectional promoters and possible pausing of the CREB protein after initial
      transcriptional activation. Also, this combined approach demonstrates the ability
      to more broadly characterize CREB protein-DNA interactions wherein not only DNA
      binding sites are discovered, but also the potential of the promoter sequence to
      respond to CREB is evaluated.

PMID- 19860900
TI  - Two treatments, one disease: childhood malaria management in Tanga, Tanzania.
AB  - BACKGROUND: In the Tanga District of coastal Tanzania, malaria is one of the
      primary causes of mortality for children under the age of five. While some
      children are treated with malaria medications in biomedical facilities, as the
      World Health Organization recommends, others receive home-care or treatment from
      traditional healers. Recognition of malaria is difficult because symptoms can
      range from fever with uncomplicated malaria to convulsions with severe malaria.
      This study explores why caregivers in the Tanga District of Tanzania pursue
      particular courses of action to deal with malaria in their children. METHODS:
      Qualitative data were collected through interviews with three samples: female
      caregivers of children under five (N = 61), medical practitioners (N = 28), and
      traditional healers (N = 18) in urban, peri-urban, and rural areas. The female
      caregiver sample is intentionally stratified to reflect the greater population of
      the Tanga District in level of education, marital status, gender of household
      head, religion, and tribal group affiliation. Qualitative data were counted,
      coded and analysed using NVivo7 software. RESULTS: Results indicate that a
      variety of factors influence treatment choice, including socio-cultural beliefs
      about malaria symptoms, associations with spiritual affliction requiring
      traditional healing, knowledge of malaria, and fear of certain anti-malaria
      treatment procedures. Most notably, some caregivers identified convulsions as a
      spiritual condition, unrelated to malaria. While nearly all caregivers reported
      attending biomedical facilities to treat children with fever (N = 60/61), many
      caregivers stated that convulsions are best treated by traditional healers (N =
      26/61). Qualitative interviews with medical practitioners and traditional healers
      confirmed this belief. CONCLUSION: Results offer insight into current trends in
      malaria management and have implications in healthcare policy, educational
      campaigns, and the importance of integrating traditional and biomedical
      approaches.

PMID- 19860901
TI  - Interacting with the biomolecular solvent accessible surface via a haptic
      feedback device.
AB  - BACKGROUND: From the 1950s computer based renderings of molecules have been
      produced to aid researchers in their understanding of biomolecular structure and
      function. A major consideration for any molecular graphics software is the
      ability to visualise the three dimensional structure of the molecule.
      Traditionally, this was accomplished via stereoscopic pairs of images and later
      realised with three dimensional display technologies. Using a haptic feedback
      device in combination with molecular graphics has the potential to enhance three
      dimensional visualisation. Although haptic feedback devices have been used to
      feel the interaction forces during molecular docking they have not been used
      explicitly as an aid to visualisation. RESULTS: A haptic rendering application
      for biomolecular visualisation has been developed that allows the user to gain
      three-dimensional awareness of the shape of a biomolecule. By using a water
      molecule as the probe, modelled as an oxygen atom having hard-sphere interactions
      with the biomolecule, the process of exploration has the further benefit of being
      able to determine regions on the molecular surface that are accessible to the
      solvent. This gives insight into how awkward it is for a water molecule to gain
      access to or escape from channels and cavities, indicating possible entropic
      bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor
      SAD, it was found that there is a channel just wide enough for a single water
      molecule to pass through. Placing the probe coincident with crystallographic
      water molecules suggests that they are sometimes located within small pockets
      that provide a sterically stable environment irrespective of hydrogen bonding
      considerations. CONCLUSION: By using the software, named HaptiMol ISAS (available
      from http://www.haptimol.co.uk), one can explore the accessible surface of
      biomolecules using a three-dimensional input device to gain insights into the
      shape and water accessibility of the biomolecular surface that cannot be so
      easily attained using conventional molecular graphics software.

PMID- 19860902
TI  - Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?
AB  - The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ
      transplantation. Both compounds are still widely used in the clinic as well as
      for basic research, even though they have dramatic side effects and modulate
      other pathways than calcineurin-NFATc, too. To answer the major open question -
      whether the adverse side effects are secondary to the actions of the drugs on the
      calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal
      inhibitors should discriminate between the inhibition of (i) calcineurin and
      peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and
      FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii)
      NFATc and other transcription factors. In this review we summarize the current
      knowledge about novel inhibitors, synthesized or identified in the last decades,
      and focus on their mode of action, specificity, and biological effects.

PMID- 19860903
TI  - Targeting tumorigenesis: development and use of mTOR inhibitors in cancer
      therapy.
AB  - The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine
      protein kinase positioned at a central point in a variety of cellular signaling
      cascades. The established involvement of mTOR activity in the cellular processes
      that contribute to the development and progression of cancer has identified mTOR
      as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including
      temsirolimus, everolimus, and ridaforolimus (formerly deforolimus) have been
      developed and assessed for their safety and efficacy in patients with cancer.
      Temsirolimus is an intravenously administered agent approved by the US Food and
      Drug Administration (FDA) and the European Medicines Agency (EMEA) for the
      treatment of advanced renal cell carcinoma (RCC). Everolimus is an oral agent
      that has recently obtained US FDA and EMEA approval for the treatment of advanced
      RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not
      yet approved for any indication. The use of mTOR inhibitors, either alone or in
      combination with other anticancer agents, has the potential to provide anticancer
      activity in numerous tumor types. Cancer types in which these agents are under
      evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma,
      hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial
      cancer, and non-small-cell lung cancer. The results of ongoing clinical trials
      with mTOR inhibitors, as single agents and in combination regimens, will better
      define their activity in cancer.

PMID- 19860904
TI  - Hypothalamic FTO is associated with the regulation of energy intake not feeding
      reward.
AB  - BACKGROUND: Polymorphism in the FTO gene is strongly associated with obesity, but
      little is known about the molecular bases of this relationship. We investigated
      whether hypothalamic FTO is involved in energy-dependent overconsumption of food.
      We determined FTO mRNA levels in rodent models of short- and long-term intake of
      palatable fat or sugar, deprivation, diet-induced increase in body weight,
      baseline preference for fat versus sugar as well as in same-weight animals
      differing in the inherent propensity to eat calories especially upon availability
      of diverse diets, using quantitative PCR. FTO gene expression was also studied in
      organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine.
      In situ hybridization (ISH) was utilized to study FTO signal in reward- and
      hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos
      immunoreactivity in FTO cells at initiation and termination of a meal. RESULTS:
      Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of
      palatable diets or macronutrient preference did not affect FTO expression.
      However, the propensity to ingest more energy without an effect on body weight
      was associated with lower FTO mRNA levels. We found that 4-fold higher number of
      FTO cells displayed c-Fos at meal termination as compared to initiation in the
      paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO
      is present mainly in hunger-related sites and it shows a high degree of
      colocalization with anorexigenic oxytocin. CONCLUSION: We conclude that FTO mRNA
      is present mainly in sites related to hunger/satiation control; changes in
      hypothalamic FTO expression are associated with cues related to energy intake
      rather than feeding reward. In line with that, neurons involved in feeding
      termination express FTO. Interestingly, baseline FTO expression appears linked
      not only with energy intake but also energy metabolism.

PMID- 19860905
TI  - Application of a high throughput Alamar blue biofilm susceptibility assay to
      Staphylococcus aureus biofilms.
AB  - BACKGROUND: Staphylococcus aureus and S. epidermidis biofilms differ in
      structure, growth and regulation, and thus the high-throughput method of
      evaluating biofilm susceptibility that has been published for S. epidermidis
      cannot be applied to S. aureus without first evaluating the assay's
      reproducibility and reliability with S. aureus biofilms. METHODS: Staphylococcus
      aureus biofilms were treated with eleven approved antibiotics, lysostaphin, or
      Conflikt, exposed to the oxidation reduction indicator Alamar blue, and reduction
      relative to untreated controls was determined visually and
      spectrophotometrically. The minimum biofilm inhibitory concentration (MBIC) was
      defined as < or = 50% Alamar blue reduction and a purple/blue well 60 min after
      the addition of Alamar blue. Because all of the approved antibiotics had MBICs
      >128 microg/ml (most >2048 microg/ml), lysostaphin and Conflikt, with relatively
      low MBICs, were used to correlate Alamar blue reduction with 2,3-bis(2-methoxy-4
      nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction and viable
      counts (CFU/ml) for S. aureus ATCC 29213 and three clinical isolates. Alamar
      blue's stability and lack of toxicity allowed CFU/ml to be determined from the
      same wells as Alamar blue absorbances. RESULTS: Overall, Alamar blue reduction
      had excellent correlation with XTT reduction and with CFU/ml. For ATCC 29213 and
      two clinical isolates treated with lysostaphin or Conflikt, Alamar blue reduction
      had excellent correlation with XTT reduction (r = 0.93-0.99) and with CFU/ml (r =
      0.92-0.98). For one of the clinical isolates, the results were moderately
      correlated for Conflikt (r = 0.76, Alamar blue vs. XTT; r = 0.81, Alamar blue vs.
      CFU/ml) and had excellent correlation for lysostaphin (r = 0.95, Alamar blue vs.
      XTT; r = 0.97, Alamar blue vs. CFU/ml). CONCLUSION: A reliable, reproducible
      method for evaluating biofilm susceptibility was successfully applied to S.
      aureus biofilms. The described method provides researchers with a simple,
      nontoxic, relatively inexpensive, high throughput measure of viability after drug
      treatment. A standardized biofilm Alamar blue assay should greatly increase the
      rate of discovery of S. aureus biofilm specific agents.

PMID- 19860906
TI  - Comparing recruitment strategies in a study of acupuncture for chronic back pain.
AB  - BACKGROUND: Meeting recruitment goals is challenging for many clinical trials
      conducted in primary care populations. Little is known about how the use of
      different recruitment strategies affects the types of individuals choosing to
      participate or the conclusions of the study. METHODS: A secondary analysis was
      performed using data from participants recruited to a clinical trial evaluating
      acupuncture for chronic back pain among primary care patients in a large
      integrated health care organization. We used two recruitment methods: mailed
      letters of invitation and an advertisement in the health plan's magazine. For
      these two recruitment methods, we compared recruitment success (% randomized,
      treatment completers, drop outs and losses to follow-up), participant
      characteristics, and primary clinical outcomes. A linear regression model was
      used to test for interaction between treatment group and recruitment method.
      RESULTS: Participants recruited via mailed letters closely resembled those
      responding to the advertisement in terms of demographic characteristics, most
      aspects of their back pain history and current episode and beliefs and
      expectations about acupuncture. No interaction between method of recruitment and
      treatment group was seen, suggesting that study outcomes were not affected by
      recruitment strategy. CONCLUSION: In this trial, the two recruitment strategies
      yielded similar estimates of treatment effectiveness. However, because this
      finding may not apply to other recruitment strategies or trial circumstances,
      trials employing multiple recruitment strategies should evaluate the effect of
      recruitment strategy on outcome. TRIAL REGISTRATION: Clinical Trials.gov
      NCT00065585.

PMID- 19860907
TI  - Trade-off between morphological convergence and opportunistic diet behavior in
      fish hybrid zone.
AB  - BACKGROUND: The invasive Chondrostoma nasus nasus has colonized part of the
      distribution area of the protected endemic species Chondrostoma toxostoma
      toxostoma. This hybrid zone is a complex system where multiple effects such as
      inter-species competition, bi-directional introgression, strong environmental
      pressure and so on are combined. Why do sympatric Chondrostoma fish present a
      unidirectional change in body shape? Is this the result of inter-species
      interactions and/or a response to environmental effects or the result of trade
      offs? Studies focusing on the understanding of a trade-off between multiple
      parameters are still rare. Although this has previously been done for Cichlid
      species flock and for Darwin finches, where mouth or beak morphology were coupled
      to diet and genetic identification, no similar studies have been done for a fish
      hybrid zone in a river. We tested the correlation between morphology (body and
      mouth morphology), diet (stable carbon and nitrogen isotopes) and genomic
      combinations in different allopatric and sympatric populations for a global data
      set of 1330 specimens. To separate the species interaction effect from the
      environmental effect in sympatry, we distinguished two data sets: the first one
      was obtained from a highly regulated part of the river and the second was
      obtained from specimens coming from the less regulated part. RESULTS: The
      distribution of the hybrid combinations was different in the two part of the
      sympatric zone, whereas all the specimens presented similar overall changes in
      body shape and in mouth morphology. Sympatric specimens were also characterized
      by a larger diet behavior variance than reference populations, characteristic of
      an opportunistic diet. No correlation was established between the body shape (or
      mouth deformation) and the stable isotope signature. CONCLUSION: The Durance
      River is an untamed Mediterranean river despite the presence of numerous dams
      that split the river from upstream to downstream. The sympatric effect on
      morphology and the large diet behavior range can be explained by a tendency
      toward an opportunistic behavior of the sympatric specimens. Indeed, the similar
      response of the two species and their hybrids implied an adaptation that could be
      defined as an alternative trade-off that underline the importance of epigenetics
      mechanisms for potential success in a novel environment.

PMID- 19860909
TI  - Meeting report: 2009 international conference on molecular neurodegeneration May
      18-20, 2009, Xiamen, China.
AB  - Age-related neurodegenerative diseases are great challenges as the aging
      population grows. To promote neurodegeneration research and to share recent
      progress in understanding molecular mechanisms underlying these devastating
      diseases, the journal Molecular Neurodegeneration and Institute for Biomedical
      Research, Xiamen University co-organized the 2009 International Conference on
      Molecular Neurodegeneration in Xiamen, China on May 18-20, 2009. The objectives
      of this meeting were to (1) promote cutting-edge neurodegeneration research in
      China and in neighboring Asian countries; (2) facilitate the exchange of
      information relevant to neurodegenerative research; (3) provide education
      opportunity for students, postdocs and physicians; and (4) provide a platform for
      investigators at different career levels to interact and network, and to foster
      collaborations at the international levels. About 100 investigators presented
      their recent discoveries with a wide range of scopes of neurodegeneration
      research, including new genes, molecular pathways, animal models, and potential
      therapeutics.

PMID- 19860908
TI  - The inhibitory receptor LILRB4 (ILT3) modulates antigen presenting cell phenotype
      and, along with LILRB2 (ILT4), is upregulated in response to Salmonella
      infection.
AB  - BACKGROUND: Leukocyte Ig-like receptors (LILR) are a family of innate immune
      receptors with immunomodulatory functions. High-level expression of the receptors
      LILRB2 (ILT4) and LILRB4 (ILT3) is a feature of tolerogenic antigen presenting
      cells and has been observed in cancer and transplant situations. There are
      relatively few studies regarding these receptors in the context of infection and
      it is not yet clear how LILRB4 exerts its inhibitory effects. RESULTS: We studied
      the effects of LILRB4 ligation on antigen presenting cell phenotype, and the
      expression of LILRB2 and LILRB4 on Salmonella-infected antigen presenting cells.
      Ligation of LILRB4 throughout in vitro culture of dendritic cells led to an
      upregulation of the co-stimulatory protein CD86. Alterations in the production of
      IL-8 and IL-10 by LILRB4-ligated macrophages were also observed. Infection with
      Salmonella typhimurium or TLR stimulation with Salmonella components led to an
      upregulation of LILRB2 and LILRB4. CONCLUSION: Our results indicate that the
      inhibitory effects of LILRB4 do not result from a failure to upregulate co
      stimulatory proteins. In addition to the high level expression that can render
      antigen presenting cells tolerogenic, there may be a role for lower level
      expression and activity of LILRB2 and LILRB4 in response to TLR signalling during
      an immune response to bacterial infection.

PMID- 19860910
TI  - phyloXML: XML for evolutionary biology and comparative genomics.
AB  - BACKGROUND: Evolutionary trees are central to a wide range of biological studies.
      In many of these studies, tree nodes and branches need to be associated (or
      annotated) with various attributes. For example, in studies concerned with
      organismal relationships, tree nodes are associated with taxonomic names, whereas
      tree branches have lengths and oftentimes support values. Gene trees used in
      comparative genomics or phylogenomics are usually annotated with taxonomic
      information, genome-related data, such as gene names and functional annotations,
      as well as events such as gene duplications, speciations, or exon shufflings,
      combined with information related to the evolutionary tree itself. The data
      standards currently used for evolutionary trees have limited capacities to
      incorporate such annotations of different data types. RESULTS: We developed a XML
      language, named phyloXML, for describing evolutionary trees, as well as various
      associated data items. PhyloXML provides elements for commonly used items, such
      as branch lengths, support values, taxonomic names, and gene names and
      identifiers. By using "property" elements, phyloXML can be adapted to novel and
      unforeseen use cases. We also developed various software tools for reading,
      writing, conversion, and visualization of phyloXML formatted data. CONCLUSION:
      PhyloXML is an XML language defined by a complete schema in XSD that allows
      storing and exchanging the structures of evolutionary trees as well as associated
      data. More information about phyloXML itself, the XSD schema, as well as tools
      implementing and supporting phyloXML, is available at http://www.phyloxml.org.

PMID- 19860911
TI  - Variation in cytokine genes can contribute to severity of acetabular osteolysis
      and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic
      association study.
AB  - BACKGROUND: The differences in total hip arthroplasty (THA) survivorship may be
      influenced by individual susceptibility to periprosthetic osteolysis. This may be
      driven by functional polymorphisms in the genes for cytokines and cytokine
      receptors involved in the development of osteolysis in THA, thereby having an
      effect on the individual's phenotype. METHODS: We performed a study on 22 single
      nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor
      candidate genes for association with severity of acetabular osteolysis and risk
      to failure in THA. Samples from 205 unrelated Caucasian patients with cementless
      type THA (ABG 1) were investigated. Distribution of investigated SNP variants
      between the groups of mild and severe acetabular osteolysis was determined by
      univariate and multivariate analysis. Time-dependent output variables were
      analyzed by the Cox hazards model. RESULTS: Univariate analysis showed: 1) TNF
      238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, p =
      0.005, population attributable risk, PAR 5.2%); 2) carriers of the IL6-174*G
      allele were 2.5 times more prone to develop severe osteolysis than non-carriers
      (OR = 2.51, p = 0.007, PAR = 31.5%); 3) the carriage of IL2-330*G allele was
      associated with protection from severe osteolysis (OR = 0.55, p = 0.043). Based
      on logistic regression, the alleles TNF-238*A and IL6-174*G were independent
      predictors for the development of severe acetabular osteolysis. Carriers of TNF
      238*A had increased cumulative hazard of THA failure according to Cox model (p =
      0.024). In contrast, IL2-330*G allele predicted lower cumulative hazard of THA
      failure (p = 0.019). CONCLUSION: Genetic variants of proinflammatory cytokines
      TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of
      the minor TNF allele could increase the cumulative risk of THA failure.
      Conversely, SNP in the IL2 gene may protect carriers from the above THA
      complications.

PMID- 19860912
TI  - Estimating cardiovascular risk in patients with type 2 diabetes: a national
      multicenter study in Brazil.
AB  - According to Brazilian National Data Survey diabetes is the fifth cause for
      hospitalization and is one of the ten major causes of mortality in this country.
      AIMS: to stratify the estimated cardiovascular risk (eCVR) in a population of
      type 2 diabetics (T2DM) according to the Framingham prediction equations as well
      as to determine the association between eCVR with metabolic and clinical control
      of the disease. METHODS: From 2000 to 2001 a cross-sectional multicenter study
      was conducted in 13 public out-patients diabetes/endocrinology clinics from 8
      Brazilian cities. The 10-year risk of developing coronary heart disease (CHD) was
      estimated by the prediction equations described by Wilson et al (Circulation
      1998). LDL equations were preferably used; when patients missed LDL data we used
      total cholesterol equations instead. RESULTS: Data from 1382 patients (59.0%
      female) were analyzed. Median and inter-quartile range (IQ) of age and duration
      of diabetes were 57.4 (51-65) and 8.8 (3-13) years, respectively without
      differences according to the gender. Forty-two percent of these patients were
      overweight and 35.4% were obese (the prevalence of higher BMI and obesity in this
      T2DM group was significantly higher in women than in men; p < 0.001). The overall
      estimated eCVR in T2DM patients was 21.4 (13.5-31.3). The eCVR was high (> 20%)
      in 738 (53.4%), intermediate in 202 (14.6%) and low in 442 (32%) patients. Men
      [25.1(15.4-37.3)] showed a higher eCVR than women [18.8 (12.4-27.9) p < 0.001].
      The most common risk factor was high LDL-cholesterol (80.8%), most frequently
      found in women than in men (p = 0.01). The median of risk factors present was
      three (2-4) without gender differences. Overall we observed that 60 (4.3%) of our
      patients had none, 154(11.1%) one, 310 (22.4%) two, 385 (27.9%) three, 300
      (21.7%) four, 149 (10.5%) five and six, (2%) six risk factors. A higher eCVR was
      noted in overweight or obese patients (p = 0.01 for both groups). No association
      was found between eCVR with age or a specific type of diabetes treatment. A
      correlation was found between eCVR and duration of diabetes (p < 0.001), BMI (p <
      0.001), creatinine (p < 0.001) and triglycerides levels (p < 0.001) but it was
      not found with HbA1c, fasting blood glucose and post-prandial glucose. A higher
      eCVR was observed in patients with retinopathy (p < 0.001) and a tendency in
      patients with microalbuminuria (p = 0.06). CONCLUSION: our study showed that in
      this group of Brazilian T2DM the eCVR was correlated with the lipid profile and
      it was higher in patients with microvascular chronic complications. No
      correlation was found with glycemic control parameters. These data could explain
      the failure of intensive glycemic control programs aiming to reduce
      cardiovascular events observed in some studies.

PMID- 19860913
TI  - Combined treatment with lexatumumab and irradiation leads to strongly increased
      long term tumour control under normoxic and hypoxic conditions.
AB  - PURPOSE: The combination of ionizing radiation with the pro-apoptotic TRAIL
      receptor antibody lexatumumab has been shown to exert considerable synergistic
      apoptotic effects in vitro and in short term growth delay assays. To clarify the
      relevance of these effects on local tumour control long-term experiments using a
      colorectal xenograft model were conducted. MATERIALS AND METHODS: Colo205
      xenograft bearing NMRI (nu/nu) nude mice were treated with fractionated
      irradiation (5x 3 Gy, d1-5) and lexatumumab (0.75 mg/kg, d1, 4 and 8). The tumour
      bearing hind limbs were irradiated with graded single top up doses at d8 under
      normoxic (ambient) and acute hypoxic (clamped) conditions. Experimental animals
      were observed for 270 days. Growth delay and local tumour control were end points
      of the study. Statistical analysis of the experiments included evaluation of
      tumour regrowth and local tumour control. RESULTS: Combined treatment with
      irradiation and lexatumumab led to a pronounced tumour regrowth-delay when
      compared to irradiation alone. The here presented long-term experiments revealed
      a highly significant rise of local tumour control for normoxic (ambient) (p = 0.
      000006) and hypoxic treatment (p = 0. 000030). CONCLUSION: Our data show that a
      combination of the pro-apoptotic antibody lexatumumab with irradiation reduces
      tumour regrowth and leads to a highly increased local tumour control in a nude
      mouse model. This substantial effect was observed under ambient and more
      pronounced under hypoxic conditions.

PMID- 19860914
TI  - Age-dependent resistance to Porcine reproductive and respiratory syndrome virus
      replication in swine.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes a
      prolonged, economically devastating infection in pigs, and immune resistance to
      infection appears variable. Since the porcine adaptive immune system is not fully
      competent at birth, we hypothesized that age influences the dynamics of PRRSV
      infection. Thus, young piglets, growing 16-20-week-old finisher pigs, and mature
      third parity sows were infected with virulent or attenuated PRRSV, and the
      dynamics of viral infection, disease, and immune response were monitored over
      time. RESULTS: Virulent PRRSV infection and disease were markedly more severe and
      prolonged in young piglets than in finishers or sows. Attenuated PRRSV in piglets
      also produced a prolonged viremia that was delayed and reduced in magnitude, and
      in finishers and sows, about half the animals showed no viremia. Despite marked
      differences in infection, antibody responses were observed in all animals
      irrespective of age, with older pigs tending to seroconvert sooner and achieve
      higher antibody levels than 3-week-old animals. Interferon gamma (IFN gamma)
      secreting peripheral blood mononuclear cells were more abundant in sows but not
      specifically increased by PRRSV infection in any age group, and interleukin-10
      (IL-10) levels in blood were not correlated with PRRSV infection status.
      CONCLUSION: These findings show that animal age, perhaps due to increased innate
      immune resistance, strongly influences the outcome of acute PRRSV infection,
      whereas an antibody response is triggered at a low threshold of infection that is
      independent of age. Prolonged infection was not due to IL-10-mediated
      immunosuppression, and PRRSV did not elicit a specific IFN gamma response,
      especially in non-adult animals. Equivalent antibody responses were elicited in
      response to virulent and attenuated viruses, indicating that the antigenic mass
      necessary for an immune response is produced at a low level of infection, and is
      not predicted by viremic status. Thus, viral replication was occurring in lung or
      lymphoid tissues even though viremia was not always observed.

PMID- 19860916
TI  - Progranulin is expressed within motor neurons and promotes neuronal cell
      survival.
AB  - BACKGROUND: Progranulin is a secreted high molecular weight growth factor bearing
      seven and one half copies of the cysteine-rich granulin-epithelin motif. While
      inappropriate over-expression of the progranulin gene has been associated with
      many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and
      development of a form of dementia (frontotemporal lobar degeneration with
      ubiquitin positive inclusions, FTLD-U) associated with the formation of
      ubiquitinated inclusions. Recent reports indicate that progranulin has
      neurotrophic effects, which, if confirmed would make progranulin the only
      neuroprotective growth factor that has been associated genetically with a
      neurological disease in humans. Preliminary studies indicated high progranulin
      gene expression in spinal cord motor neurons. However, it is uncertain what the
      role of Progranulin is in normal or diseased motor neuron function. We have
      investigated progranulin gene expression and subcellular localization in cultured
      mouse embryonic motor neurons and examined the effect of progranulin over
      expression and knockdown in the NSC-34 immortalized motor neuron cell line upon
      proliferation and survival. RESULTS: In situ hybridisation and
      immunohistochemical techniques revealed that the progranulin gene is highly
      expressed by motor neurons within the mouse spinal cord and in primary cultures
      of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal
      microscopy coupled to immunocytochemistry together with the use of a progranulin
      green fluorescent protein fusion construct revealed progranulin to be located
      within compartments of the secretory pathway including the Golgi apparatus.
      Stable transfection of the human progranulin gene into the NSC-34 motor neuron
      cell line stimulates the appearance of dendritic structures and provides
      sufficient trophic stimulus to survive serum deprivation for long periods (up to
      two months). This is mediated at least in part through an anti-apoptotic
      mechanism. Control cells, while expressing basal levels of progranulin do not
      survive in serum free conditions. Knockdown of progranulin expression using shRNA
      technology further reduced cell survival. CONCLUSION: Neurons are among the most
      long-lived cells in the body and are subject to low levels of toxic challenges
      throughout life. We have demonstrated that progranulin is abundantly expressed in
      motor neurons and is cytoprotective over prolonged periods when over-expressed in
      a neuronal cell line. This work highlights the importance of progranulin as
      neuroprotective growth factor and may represent a therapeutic target for
      neurodegenerative diseases including motor neuron disease.

PMID- 19860917
TI  - Comparative study of enteric viruses, coliphages and indicator bacteria for
      evaluating water quality in a tropical high-altitude system.
AB  - BACKGROUND: Bacteria used as indicators for pathogenic microorganisms in water
      are not considered adequate as enteric virus indicators. Surface water from a
      tropical high-altitude system located in Mexico City that receives rainwater,
      treated and non-treated wastewater used for irrigation, and groundwater used for
      drinking, was studied. METHODS: The presence of enterovirus, rotavirus,
      astrovirus, coliphage, coliform bacteria, and enterococci was determined during
      annual cycles in 2001 and 2002. Enteric viruses in concentrated water samples
      were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).
      Coliphages were detected using the double agar layer method. Bacteria analyses of
      the water samples were carried out by membrane filtration. RESULTS: The presence
      of viruses and bacteria in the water used for irrigation showed no relationship
      between current bacterial indicator detection and viral presence. Coliphages
      showed strong association with indicator bacteria and enterovirus, but weak
      association with other enteric viruses. Enterovirus and rotavirus showed
      significant seasonal differences in water used for irrigation, although this was
      not clear for astrovirus. CONCLUSION: Coliphages proved to be adequate faecal
      pollution indicators for the irrigation water studied. Viral presence in this
      tropical high-altitude system showed a similar trend to data previously reported
      for temperate zones.

PMID- 19860915
TI  - Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA
      trial.
AB  - BACKGROUND: The randomized placebo-controlled IFIGENIA-trial demonstrated that
      therapy with high-dose N-acetylcysteine (NAC) given for one year, added to
      prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease
      progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco)
      (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical
      implications of these findings we performed additional, explorative analyses of
      the IFGENIA data set. METHODS: We analysed effects of NAC on VC, DLco, a
      composite physiologic index (CPI), and mortality in the 155 study-patients.
      RESULTS: In trial completers the functional indices did not change significantly
      with NAC, whereas most indices deteriorated with placebo; in non-completers the
      majority of indices worsened but decline was generally less pronounced in most
      indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI
      also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI
      were significantly better if the baseline CPI was 50 points or lower. CONCLUSION:
      This descriptive analysis confirms and extends the favourable effects of NAC on
      lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for
      the evaluation of a therapeutic effect. Most importantly, less progressed disease
      as indicated by a CPI of 50 points or lower at baseline was more responsive to
      therapy in this study.

PMID- 19860918
TI  - Developing capacity in health informatics in a resource poor setting: lessons
      from Peru.
AB  - The public sectors of developing countries require strengthened capacity in
      health informatics. In Peru, where formal university graduate degrees in
      biomedical and health informatics were lacking until recently, the AMAUTA Global
      Informatics Research and Training Program has provided research and training for
      health professionals in the region since 1999. The Fogarty International Center
      supports the program as a collaborative partnership between Universidad Peruana
      Cayetano Heredia in Peru and the University of Washington in the United States of
      America. The program aims to train core professionals in health informatics and
      to strengthen the health information resource capabilities and accessibility in
      Peru. The program has achieved considerable success in the development and
      institutionalization of informatics research and training programs in Peru.
      Projects supported by this program are leading to the development of sustainable
      training opportunities for informatics and eight of ten Peruvian fellows trained
      at the University of Washington are now developing informatics programs and an
      information infrastructure in Peru. In 2007, Universidad Peruana Cayetano Heredia
      started offering the first graduate diploma program in biomedical informatics in
      Peru.

PMID- 19860919
TI  - Inherent promoter bidirectionality facilitates maintenance of sequence integrity
      and transcription of parasitic DNA in mammalian genomes.
AB  - BACKGROUND: Many mammalian genes are arranged in a bidirectional manner, sharing
      a common promoter and regulatory elements. This is especially true for promoters
      containing a CpG island, usually unmethylated and associated with an 'open' or
      accessible chromatin structure. In evolutionary terms, a primary function of
      genomic methylation is postulated to entail protection of the host genome from
      the disruption associated with activity of parasitic or transposable elements.
      These are usually epigenetically silenced following insertion into mammalian
      genomes, becoming sequence degenerate over time. Despite this, it is clear that
      many transposable element-derived DNAs have evaded host-mediated epigenetic
      silencing to remain expressed (domesticated) in mammalian genomes, several of
      which have demonstrated essential roles during mammalian development. RESULTS:
      The current study provides evidence that many CpG island-associated promoters
      associated with single genes exhibit inherent bidirectionality, facilitating
      "hijack" by transposable elements to create novel antisense 'head-to-head'
      bidirectional gene pairs in the genome that facilitates escape from host-mediated
      epigenetic silencing. This is often associated with an increase in CpG island
      length and transcriptional activity in the antisense direction. From a list of
      over 60 predicted protein-coding genes derived from transposable elements in the
      human genome and 40 in the mouse, we have found that a significant proportion are
      orientated in a bidirectional manner with CpG associated regulatory regions.
      CONCLUSION: These data strongly suggest that the selective force that shields
      endogenous CpG-containing promoter from epigenetic silencing can extend to
      exogenous foreign DNA elements inserted in close proximity in the antisense
      orientation, with resulting transcription and maintenance of sequence integrity
      of such elements in the host genome. Over time, this may result in
      "domestication" of such elements to provide novel cellular and developmental
      functions.

PMID- 19860920
TI  - Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests
      for the diagnosis of falciparum and vivax malaria.
AB  - BACKGROUND: In areas where non-falciparum malaria is common rapid diagnostic
      tests (RDTs) capable of distinguishing malaria species reliably are needed. Such
      tests are often based on the detection of parasite lactate dehydrogenase (pLDH).
      METHODS: In Dawei, southern Myanmar, three pLDH based RDTs (CareStart Malaria
      pLDH (Pan), CareStart Malaria pLDH (Pan, Pf) and OptiMAL-IT)were evaluated in
      patients presenting with clinically suspected malaria. Each RDT was read
      independently by two readers. A subset of patients with microscopically confirmed
      malaria had their RDTs repeated on days 2, 7 and then weekly until negative. At
      the end of the study, samples of study batches were sent for heat stability
      testing. RESULTS: Between August and November 2007, 1004 patients aged between 1
      and 93 years were enrolled in the study. Slide microscopy (the reference
      standard) diagnosed 213 Plasmodium vivax (Pv) monoinfections, 98 Plasmodium
      falciparum (Pf) mono-infections and no malaria in 650 cases. The sensitivities
      (sens) and specificities (spec), of the RDTs for the detection of malaria were-
      CareStart Malaria pLDH (Pan) test: sens 89.1% [CI95 84.2-92.6], spec 97.6% [CI95
      96.5-98.4]. OptiMal-IT: Pf+/- other species detection: sens 95.2% [CI95 87.5
      98.2], spec 94.7% [CI95 93.3-95.8]; non-Pf detection alone: sens 89.6% [CI95 83.6
      93.6], spec 96.5% [CI95 94.8-97.7]. CareStart Malaria pLDH (Pan, Pf): Pf+/- other
      species: sens 93.5% [CI95 85.4-97.3], spec 97.4% [95.9-98.3]; non-Pf: sens 78.5%
      [CI95 71.1-84.4], spec 97.8% [CI95 96.3-98.7]. Inter-observer agreement was
      excellent for all tests (kappa > 0.9). The median time for the RDTs to become
      negative was two days for the CareStart Malaria tests and seven days for OptiMAL
      IT. Tests were heat stable up to 90 days except for OptiMAL-IT (Pf specific pLDH
      stable to day 20 at 35 degrees C). CONCLUSION: None of the pLDH-based RDTs
      evaluated was able to detect non-falciparum malaria with high sensitivity,
      particularly at low parasitaemias. OptiMAL-IT performed best overall and would
      perform best in an area of high malaria prevalence among screened fever cases.
      However, heat stability was unacceptable and the number of steps to perform this
      test is a significant drawback in the field. A reliable, heat-stable, highly
      sensitive RDT, capable of diagnosing all Plasmodium species has yet to be
      identified.

PMID- 19860921
TI  - Remarkable sequence similarity between the dinoflagellate-infecting marine girus
      and the terrestrial pathogen African swine fever virus.
AB  - Heterocapsa circularisquama DNA virus (HcDNAV; previously designated as HcV) is a
      giant virus (girus) with a approximately 356-kbp double-stranded DNA (dsDNA)
      genome. HcDNAV lytically infects the bivalve-killing marine dinoflagellate H.
      circularisquama, and currently represents the sole DNA virus isolated from
      dinoflagellates, one of the most abundant protists in marine ecosystems. Its
      morphological features, genome type, and host range previously suggested that
      HcDNAV might be a member of the family Phycodnaviridae of Nucleo-Cytoplasmic
      Large DNA Viruses (NCLDVs), though no supporting sequence data was available.
      NCLDVs currently include two families found in aquatic environments
      (Phycodnaviridae, Mimiviridae), one mostly infecting terrestrial animals
      (Poxviridae), another isolated from fish, amphibians and insects (Iridoviridae),
      and the last one (Asfarviridae) exclusively represented by the animal pathogen
      African swine fever virus (ASFV), the agent of a fatal hemorrhagic disease in
      domestic swine. In this study, we determined the complete sequence of the type B
      DNA polymerase (PolB) gene of HcDNAV. The viral PolB was transcribed at least
      from 6 h post inoculation (hpi), suggesting its crucial function for viral
      replication. Most unexpectedly, the HcDNAV PolB sequence was found to be closely
      related to the PolB sequence of ASFV. In addition, the amino acid sequence of
      HcDNAV PolB showed a rare amino acid substitution within a motif containing
      highly conserved motif: YSDTDS was found in HcDNAV PolB instead of YGDTDS in most
      dsDNA viruses. Together with the previous observation of ASFV-like sequences in
      the Sorcerer II Global Ocean Sampling metagenomic datasets, our results further
      reinforce the ideas that the terrestrial ASFV has its evolutionary origin in
      marine environments.

PMID- 19860922
TI  - Lowering the glycemic index of white bread using a white bean extract.
AB  - BACKGROUND: Phase 2((R)) is a dietary supplement derived from the common white
      kidney bean (Phaseolus vulgaris). Phase 2 has been shown to inhibit alpha
      amylase, the complex carbohydrate digesting enzyme, in vitro. The inhibition of
      alpha-amylase may result in the lowering of the effective Glycemic Index (GI) of
      certain foods. The objective of this study was to determine whether the addition
      of Phase 2 would lower the GI of a commercially available high glycemic food
      (white bread). METHODS: An open-label 6-arm crossover study was conducted with 13
      randomized subjects. Standardized GI testing was performed on white bread with
      and without the addition of Phase 2 in capsule and powder form, each in dosages
      of 1500 mg, 2000 mg, and 3000 mg. Statistical analysis was performed by one-way
      ANOVA of all seven treatment groups using unadjusted multiple comparisons (t
      tests) to the white bread control. RESULTS: For the capsule formulation, the 1500
      mg dose had no effect on the GI and the 2000 mg and 3000 mg capsule doses caused
      insignificant reductions in GI. For the powder, the 1500 mg and 2000 mg doses
      caused insignificant reductions in the GI, and the 3000 mg dose had a significant
      effect (-20.23 or 34.11%, p = 0.023) CONCLUSION: Phase 2 white bean extract
      appears to be a novel and potentially effective method for reducing the GI of
      existing foods without modifying their ingredient profile. TRIAL REGISTRATION:
      Trial Registration: ISRCTN50347345.

PMID- 19860923
TI  - Comparative functional analysis of Jembrana disease virus Tat protein on
      lentivirus long terminal repeat promoters: evidence for flexibility at its N
      terminus.
AB  - BACKGROUND: Jembrana disease virus (JDV) encodes a potent regulatory protein Tat
      that strongly stimulates viral expression by transactivating the long terminal
      repeat (LTR) promoter. JDV Tat (jTat) promotes the transcription from its own LTR
      as well as non-cognate LTRs, by recruiting host transcription factors and
      facilitating transcriptional elongation. Here, we compared the sequence
      requirements of jTat for transactivation of JDV, bovine immunodeficiency virus
      (BIV) and human immunodeficiency virus (HIV) LTRs. RESULTS: In this study, we
      identified the minimal protein sequence for LTR activation using jTat truncation
      mutants. We found that jTat N-terminal residues were indispensable for
      transactivating the HIV LTR. In contrast, transactivation of BIV and JDV LTRs
      depended largely on an arginine-rich motif and some flanking residues.
      Competitive inhibition assay and knockdown analysis showed that P-TEFb was
      required for jTat-mediated LTR transactivation, and a mammalian two-hybrid assay
      revealed the robust interaction of jTat with cyclin T1. In addition, HIV LTR
      transactivation was largely affected by fusion protein at the jTat N-terminus
      despite the fact that the cyclin T1-binding affinity was not altered.
      Furthermore, the jTat N-terminal sequence enabled HIV Tat to transactivate BIV
      and JDV LTRs, suggesting the flexibility at the jTat N-terminus. CONCLUSION: This
      study showed the distinct sequence requirements of jTat for HIV, BIV and JDV LTR
      activation. Residues responsible for interaction with cyclin T1 and
      transactivation response element are the key determinants for transactivation of
      its cognate LTR. N-terminal residues in jTat may compensate for transactivation
      of the HIV LTR, based on the flexibility.

PMID- 19860924
TI  - Classification of BMI control commands from rat's neural signals using extreme
      learning machine.
AB  - A recently developed machine learning algorithm referred to as Extreme Learning
      Machine (ELM) was used to classify machine control commands out of time series of
      spike trains of ensembles of CA1 hippocampus neurons (n = 34) of a rat, which was
      performing a target-to-goal task on a two-dimensional space through a brain
      machine interface system. Performance of ELM was analyzed in terms of training
      time and classification accuracy. The results showed that some processes such as
      class code prefix, redundancy code suffix and smoothing effect of the
      classifiers' outputs could improve the accuracy of classification of robot
      control commands for a brain-machine interface system.

PMID- 19860925
TI  - Spontaneous bleeding of an Abrikossoff's tumor--a case report.
AB  - Abrikossoff tumors are a rare tumor entity. The complication of a hemothorax has
      not been described in the literature so far. A 24-year-old patient presented with
      repeated hemoptysis and right thoracic pain. The initial CT-scan revealed a solid
      tumor mass in the right lower bronchus. After further diagnostics, the patient
      was discharged and surgical intervention was planned. He was readmitted 4 days
      after discharge with a spontaneous hemothorax. After the right lower lobectomy
      and an uneventful course the patient recovered well.

PMID- 19860927
TI  - [Too many coronary intervention centres in the Netherlands].
AB  - The Dutch Minister of Health's decision to expand the number of specialised
      treatment centres for percutaneous cardiac interventions (PCI) will reduce the
      volume per centre and per cardiologist. Hospitals and cardiologists have
      overestimated their adherence region and this will result in too few
      interventions per cardiologist to allow them to maintain their skills and
      guarantee optimal quality. Several studies show that there is a strong
      relationship between volume and complications. In acute PCI, experienced
      cardiologists have 42% (95% CI: 0.39-0.86) less mortality than their less
      experienced colleagues. The minister has defended his policy by stating that
      quality of care is the responsibility of cardiologists, directors of hospitals
      and health insurance companies. However, the branch is not able to control the
      distribution of complicated interventions. Although they know that there is a
      strong relation between the number of interventions and outcome they refuse to
      accept this and ignore the importance of forming strong alliances and
      collaborative networks.

PMID- 19860926
TI  - What you see is not what you get: implications of the brevity of antibody
      responses to malaria antigens and transmission heterogeneity in longitudinal
      studies of malaria immunity.
AB  - BACKGROUND: A major handicap in developing a malaria vaccine is the difficulty in
      pinpointing the immune responses that protect against malaria. The protective
      efficacy of natural or vaccine-induced immune responses against malaria is
      normally assessed by relating the level of the responses in an individual at the
      beginning of a follow-up period and the individual's experience of malaria
      infection or disease during the follow-up. This approach has identified a number
      of important responses against malaria, but their protective efficacies vary
      considerably between studies. HYPOTHESIS: It is likely that apart from
      differences in study methodologies, differences in exposure among study subjects
      within each study and brevity of antibody responses to malaria antigen are
      important sources of the variation in protective efficacy of anti-malaria immune
      responses mentioned above. Since malaria immunity is not complete, anyone in an
      area of stable malaria transmission who does not become asymptomatically or
      symptomatically infected during follow-up subsequent to treatment is most likely
      unexposed rather than immune. TESTING THE HYPOTHESIS: It is proposed that
      individuals involved in a longitudinal study of malaria immunity should be
      treated for malaria prior to the start of the study and only those who present
      with at least an asymptomatic infection during the follow-up should be included
      in the analysis. In addition, it is proposed that more closely repeated
      serological survey should be carried out during follow-up in order to get a
      better picture of an individual's serological status. IMPLICATIONS OF THE
      HYPOTHESIS: Failure to distinguish between individuals who do not get a clinical
      episode during follow-up because they were unexposed and those who are genuinely
      immune undermines our ability to assign a protective role to immune responses
      against malaria. The brevity of antibodies responses makes it difficult to assign
      the true serological status of an individual at any given time, i.e. those
      positive at a survey may be negative by the time they encounter the next
      infection.

PMID- 19860929
TI  - New trends in minimally invasive urological surgery.
AB  - PURPOSE: The perceived benefits of minimally-invasive surgery include less
      postoperative pain, shorter hospitalization, reduced morbidity and better
      cosmesis while maintaining diagnostic accuracy and therapeutic outcome. We review
      the new trends in minimally-invasive urological surgery. MATERIALS AND METHODS:
      We reviewed the English language literature using the National Library of
      Medicine database to identify the latest technological advances in minimally
      invasive surgery with particular reference to urology. RESULTS: Amongst other
      advances, studies incorporating needlescopic surgery, laparoendoscopic single
      site surgery , magnetic anchoring and guidance systems, natural orifice
      transluminal endoscopic surgery and flexible robots were considered of interest.
      The results from initial animal and human studies are also outlined. CONCLUSION:
      Minimally-invasive surgery continues to evolve to meet the demands of the
      operators and patients. Many novel technologies are still in the testing phase,
      whilst others have entered clinical practice. Further evaluation is required to
      confirm the safety and efficacy of these techniques and validate the published
      reports.

PMID- 19860930
TI  - Prostatic specific antigen for prostate cancer detection.
AB  - Prostate-specific antigen (PSA) has been used for prostate cancer detection since
      1994. PSA testing has revolutionized our ability to diagnose, treat, and follow
      up patients. In the last two decades, PSA screening has led to a substantial
      increase in the incidence of prostate cancer (PC). This increased detection
      caused the incidence of advanced-stage disease to decrease at a dramatic rate,
      and most newly diagnosed PC today are localized tumors with a high probability of
      cure. PSA screening is associated with a 75% reduction in the proportion of men
      who now present with metastatic disease and a 32.5% reduction in the age-adjusted
      prostate cancer mortality rate through 2003. Although PSA is not a perfect
      marker, PSA testing has limited specificity for prostate cancer detection, and
      its appropriate clinical application remains a topic of debate. Due to its
      widespread use and increased over-detection, the result has been the occurrence
      of over-treatment of indolent cancers. Accordingly, several variations as regards
      PSA measurement have emerged as useful adjuncts for prostate cancer screening.
      These procedures take into consideration additional factors, such as the
      proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B
      PSA), the prostate volume (PSA density), and the rate of change in PSA levels
      over time (PSA velocity or PSA doubling time). The history and evidence
      underlying each of these parameters are reviewed in the following article.

PMID- 19860931
TI  - Sonographic detection of renal and ureteral stones. Value of the twinkling sign.
AB  - PURPOSE: To compare the detection of urinary stones using standard gray scale
      ultrasound for diagnostic accuracy using the color Doppler "twinkling sign".
      MATERIALS AND METHODS: Our study population consisted of forty-one patients who
      demonstrated at least one urinary stone on unenhanced CT evaluation of the
      kidneys or ureters. Each patient was evaluated using gray scale ultrasound and
      color Doppler imaging by an observer who was blinded to the CT results. RESULTS:
      Seventy-seven stones were present in 41 patients, including 47 intrarenal stones,
      5 stones in the renal pelvis, 8 stones at the ureteropelvic junction, 5 ureteral
      stones and 12 stones at the ureterovesical junction. Based upon gray scale
      sonography the diagnosis of stone was made with confidence in 66% (51/77) of
      locations. Based upon Doppler sonography using the twinkling sign, the diagnosis
      of stone was made with confidence in 97% (75/77) of locations. Clustered ROC
      analysis demonstrated that the Doppler twinkling sign (Az = 0.99) was
      significantly better than conventional gray scale criteria (Az = 0.95) for the
      diagnosis of urinary stones (p = 0.005, two-sided test). CONCLUSIONS: The color
      Doppler twinkling sign improves the detection, confidence and overall accuracy of
      diagnosis for renal and ureteral stones with minimal loss of specificity.

PMID- 19860932
TI  - Patient position and semi-rigid ureteroscopy outcomes.
AB  - INTRODUCTION: Two positions have been reported for ureteroscopy (URS): dorsal
      lithotomy (DL) position and dorsal lithotomy position with same side leg slightly
      extended (DLEL). The aim of the present study was to compare the outcomes
      associated with URS performed with patients in DL vs. DLEL position. MATERIALS
      AND METHODS: A total of 98 patients treated for ureteral calculi were randomized
      to either DL or DLEL position during URS, and were prospectively followed.
      Patients, stone characteristics and operative outcomes were evaluated. RESULTS:
      Of the 98 patients included in the study, 56.1% were men and 43.9% women with a
      mean age of 42.6 +/- 16.8 years. Forty-eight patients underwent URS in DL
      position and 50 in DLEL position. Patients' age, mean stone size and location
      were similar between both groups. Operative time was longer for the DL vs. DLEL
      group (81.0 vs. 62.0 minutes, p = 0.045), mainly for men (95.2 vs. 63.9 minutes,
      p = 0.023). Mean fluoroscopy use, complications and success rates were similar
      between both groups. CONCLUSIONS: Most factors associated with operative outcomes
      during URS are inherent to patient's condition or devices available at each
      center, and therefore cannot be changed. However, leg position is a simple factor
      that can easily be changed, and directly affects operative time during URS. Even
      though success and complication rates are not related to position, placing the
      patient in dorsal lithotomy position with an extended leg seems to make the
      surgery easier and faster.

PMID- 19860933
TI  - PSA levels of 4.0 - 10 ng/mL and negative digital rectal examination. Antibiotic
      therapy versus immediate prostate biopsy.
AB  - PURPOSE: The management of mildly elevated (4.0-10.0 ng/ml) prostate specific
      antigen (PSA) is uncertain. Immediate prostate biopsy, antibiotic treatment, or
      short term monitoring PSA level for 1-3 months is still in controversy. MATERIALS
      AND METHODS: We conducted a retrospective chart review of patients in a large
      community practice (2003 - 2007) who had PSA levels between 4.0-10 ng/mL without
      any further evidence of infection. Data was gathered regarding patient's age,
      whether standard antibiotic therapy (10-14 days of ofloxacin or ciprofloxacin)
      had been administered before the second PSA measurement, results of a second PSA
      test performed at 1- to 2-month intervals, whether a prostate biopsy was
      performed and its result. RESULTS: One-hundred and thirty-five men met the study
      inclusion criteria with 65 (48.1%) having received antibiotics (group 1); the PSA
      levels decreased in 39 (60%) of which, sixteen underwent a biopsy which
      demonstrated prostate cancer in 4 (25%). Twenty-six (40%) patients of group 1
      exhibited no decrease in PSA levels; seventeen of them underwent a biopsy that
      demonstrated cancer in 2 (12%). The other 70 (51.9%) patients were not treated
      with antibiotics (group 2); the PSA levels decreased in 42 (60%) of which,
      thirteen underwent a biopsy which demonstrated prostate cancer in 4 (31%). In the
      other 28 (40%) patients of group 2 there was no demonstrated decrease in PSA,
      nineteen of these subjects underwent a biopsy that demonstrated cancer in 8
      (42%). CONCLUSIONS: There appears to be no advantage for administration of
      antibacterial therapy with initial PSA levels between 4-10 ng/mL without overt
      evidence of inflammation.

PMID- 19860934
TI  - Gleason score and laterality concordance between prostate biopsy and
      prostatectomy specimens.
AB  - OBJECTIVES: Prostate biopsy involvement and Gleason score guide treatment
      decisions in prostate cancer. We evaluated concordance in Gleason score and
      laterality between biopsy and radical retropubic prostatectomy (RRP) specimens
      and factors that influenced this relationship. MATERIALS AND METHODS: We reviewed
      538 prostate cancer diagnoses at a Veterans Affairs medical center (2000-2005) to
      identify men with prostate biopsy and RRP specimens. During this time there was a
      move from limited (6 core) to extended (12 core) biopsy schemes. Discordance in
      Gleason score was defined as any change in Gleason score. RESULTS: 152 men
      underwent RRP with biopsy showing Gleason < 7 in 56%, 7 in 36%, and > 7 in 8%.
      Biopsy involvement was unilateral in 59% and bilateral in 41%. Compared to the
      biopsy, RRP Gleason score was concordant in 76 (50%), higher in 51 (34%), and
      lower in 25 (16%). Bilateral involvement was concordant in 97%, while unilateral
      involvement was concordant in only 20%. Both Gleason score and laterality were
      concordant in only 26%. Gleason concordance was higher in those with 8 or more
      cores compared to < 8 cores taken (54% vs. 34%, p = 0.046), but concordance was
      not affected by age, PSA, prostate volume, or length of time from biopsy to RRP.
      During later years, concordance did not improve despite taking more cores.
      CONCLUSIONS: Prostate biopsy underestimated prostatectomy Gleason score in 34% of
      men and bilateral involvement in 80% of those with unilateral disease on biopsy.
      Taking at least eight cores improves the accuracy of the prostate biopsy.

PMID- 19860935
TI  - Laparoscopic radical prostatectomy: 10 years experience.
AB  - PURPOSE: The authors assess the morbidity, functional results and oncologic
      follow-up of a series of laparoscopic radical prostatectomies performed in over a
      10-year period. MATERIALS AND METHODS: The data on 780 laparoscopic radical
      prostatectomies performed between September 1997 and December 2007 were stored in
      a personal database. The following parameters are described and critically
      analyzed: operative time, blood transfusions, conversions, length of hospital
      stay, complications, functional results of sexual potency and urinary continence,
      surgical margins and oncologic follow-up. RESULTS: Operative time averaged 125
      minutes, with a mean bleeding volume of 335 mL and mean hospital stay of 4.3
      days. The rate of conversion to open surgery was 1.36% and the overall
      complication rate was 14.24%. The pathology analysis showed pT2 tumors in 82.60%
      and pT3 tumors in 17.39% of cases. The overall positive margin rate was 19.58%,
      with a biochemical recurrence of 10.27% at a mean follow-up of 62.5 months.
      Urinary continence and sexual potency yielded rates of 88% and 61%, respectively,
      12 months after surgery. CONCLUSIONS: Laparoscopic radical prostatectomy is a
      technically well-defined procedure that provides good oncologic and functional
      results after proper training.

PMID- 19860936
TI  - Radioactive seed migration after prostate brachytherapy with iodine-125 using
      loose seeds versus stranded seeds.
AB  - OBJECTIVES: To assess the incidence and clinical parameters that could influence
      migration of seeds in localized prostate cancer patients treated by stranded
      versus loose sources by Iodine-125 brachytherapy. MATERIALS AND METHODS: 100
      patients were treated from January/1998 until December/2006. Age, PSA, clinical
      stage, Gleason, prostate volume, number of seeds, activity of radioactive seeds,
      and dosimetric parameters, such as V100, V150 and D90 were evaluated. RESULTS:
      Mean follow-up was 79 months (18 - 120. CI 95%: 72 - 85). Overall, 6 of 100
      patients experienced seed migration. Seed migration was found in 4/50 (8%)
      patients using loose seeds and in 2/50 (4%) treated by stranded seeds. Mean value
      dosimetric parameters for stranded seeds were greater than those for loose seeds
      (V100(%): 88.7/82, D90(Gy): 149.2/140.3, D90(%): 104.2/93.8, V150 (%): 53.8/47,
      respectively). No significant difference in migration of seeds was detected
      between loose and stranded seeds considering age (p = 0.33), PSA (p = 0.391),
      prostate volume (p = 0.397), activity of radioactive seeds (p = 0.109), number of
      seeds (p = 0.338), V100 (p = 0.332), although significant differences were
      measured in the values of D90(% and Gy) (p = 0.022 and 0.011) and V150 (p =
      0.023). CONCLUSIONS: Seed migration after brachytherapy might occur and it does
      affect post-implant dosimetry.

PMID- 19860937
TI  - Resistance of human spermatozoa to cryoinjury in repeated cycles of thaw
      refreezing.
AB  - OBJECTIVE: To study the resistance of human spermatozoa to cryoinjury in repeated
      cycles of thaw-refreezing by using the fast liquid nitrogen vapor method.
      MATERIALS AND METHODS: Semen specimens were obtained from sixteen normal and
      oligozoospermic individuals who required disposal at the sperm bank. Five of them
      had testicular cancer. Specimens were thawed and an aliquot was removed for
      analysis. The remaining specimens were refrozen without removing the cryomedia.
      Repeated freeze-thaw cycles were performed until no motile sperm were observed.
      Sperm motility, number of motile spermatozoa and viability were determined after
      thawing. Resistance to cryoinjury was compared between groups and also after each
      refreezing cycle within groups. RESULTS: Motile spermatozoa were recovered after
      five and two refreeze-thawing cycles in normozoospermic and oligozoospermic
      specimens, respectively. There were no significant differences in the recovery of
      motile spermatozoa between thaws within each group of normal and oligozoospermic
      specimens, but percentage motility and total number of motile spermatozoa were
      significantly lower in the oligozoospermic one. Specimens from men with cancer
      were exposed to six refreeze-thawing cycles. Although recovery of motile
      spermatozoa was significantly impaired after each thawing, there were no
      significant differences in the recovery of motile sperm between thaws in cancer
      and non-cancer groups. CONCLUSIONS: Human spermatozoa resist repeated
      cryopreservation using the fast liquid nitrogen vapor method. Normozoospermic
      specimens withstand refreezing for an average two cycles longer than
      oligozoospermic ones. Specimens from cancer patients seem to resist repeated
      cryoinjury similarly to non-cancer counterparts. Resistance to repeated
      cryoinjury was related to the initial semen quality.

PMID- 19860938
TI  - Prevalence and risk factors for urinary and fecal incontinence in Brazilian
      women.
AB  - OBJECTIVE: To evaluate prevalence and risk factors of fecal and urinary
      incontinence (UI) in Brazilian women. MATERIALS AND METHODS: 685 women older than
      20 years of age answered a questionnaire about urinary and fecal symptoms,
      clinical and obstetric antecedents. They were grouped according to presence or
      absence of UI. RESULTS: Urinary and fecal incontinence was reported in 27% and 2%
      of cases, respectively. Mean age of incontinent women was significantly higher
      than continent ones. Incontinent women had a mean number of micturitions
      significantly higher than the continent ones. On average, incontinent women had
      higher rate of pregnancies and vaginal delivery when compared to the continent
      ones. Body mass index (BMI) was significantly higher in incontinent participants
      and in women with no UI complaints (27.35 vs. 24.95, p < 0.05). Fecal
      incontinence prevalence was 2% and occurred exclusively in patients with UI.
      CONCLUSIONS: Vaginal delivery and high BMI have been identified as risk factors
      for UI development while aging and number of pregnancies may be correlated
      factors.

PMID- 19860939
TI  - Effects of curcumin in an orthotopic murine bladder tumor model.
AB  - Cigarette smoking (CS) is the main risk factor for bladder cancer development.
      There are more than 100 carcinogens present in cigarette smoke. Among the
      potential mediators of CS-induced alterations is nuclear factor-kappa (NF
      kappaB), which is responsible for the transcription of genes related to cell
      transformation, tumor promotion, angiogenesis, invasion and metastasis. Curcumin
      is a polyphenol compound derived from Curcuma longa that suppress cellular
      transformation, proliferation, invasion, angiogenesis, and metastasis by down
      regulating NF-kappaB and its regulated genes. The aim of our study was to assess
      the effects of curcumin in bladder urothelial carcinoma. We studied the effects
      of curcumin in vitro and in vivo using the orthotropic syngeneic bladder tumor
      animal model MB49. Curcumin promotes apoptosis of bladder tumor cells in vitro.
      In vivo tumors of animals treated with curcumin were significantly smaller as
      compared to controls. Using immunohistochemistry, we demonstrated a decrease in
      the expression of Cox-2 by 8% and Cyclin D1 by 13% in the animals treated with
      curcumin; both genes regulated by NF-kappaB and related to cell proliferation. In
      this study, we showed that curcumin acts in bladder urothelial cancer, possibly
      dowregulating NF-kappaB-related genes, and could be an option in the treatment of
      urothelial neoplasms. The results of our study suggest that further research is
      warranted to confirm our findings.

PMID- 19860940
TI  - Re: Challenging non-traumatic posterior urethral strictures treated with
      urethroplasty: a preliminary report.

PMID- 19860941
TI  - Robotic assisted laparoscopic partial cystectomy and urachal resection for
      urachal adenocarcinoma.
AB  - INTRODUCTION AND OBJECTIVE: Standard treatment for urachal adenocarcinomas is
      open partial cystectomy and urachal resection; however, minimally invasive
      surgical approaches including laparoscopic and recently described robotic
      assisted laparoscopic partial cystectomy and urachal resection is feasible with
      potential less morbidity. A case of robotic assisted partial cystectomy and
      urachal resection for urachal adenocarcinoma is presented. Few articles in the
      literature have being published describing this technique and to the best of our
      knowledge, this is the largest and potentially most complex case approached in
      such a manner. METHODS: A 55 years old African American male presented with
      hematuria and mucosuria, cystoscopy demonstrated a tumor involving the dome of
      the bladder. Transurethral biopsy confirmed a urachal adenocarcinoma. Further
      studies revealed a negative metastatic evaluation. Preoperative abdominal/pelvic
      CT imaging revealed an enhancing mass extending from the inferior level of the
      umbilicus to the dome of the bladder. A total of 6 laparoscopic ports were used.
      The robotic assisted laparoscopic dissection was started at the level of the
      umbilicus, dissecting lateral to the right and left medial umbilical ligaments up
      until the dome of the bladder. A simultaneous cystoscopy with transillumination
      to define the bladder boundaries of this mass, with robotic assisted laparoscopic
      opening of the bladder, with the entire mass (including bladder component)
      excised and sent for frozen pathology for margin evaluation. After specimen
      extraction, the bladder was closed in two layers. Total surgery time was 300
      minutes and intra-operative blood loss was 150cc. RESULTS: Final pathology
      reported a pT2N0Mx adenocarcinoma with negative margins and negative pelvic lymph
      nodes. Patient was started on clear liquids on postoperative day 2 and on regular
      diet on postoperative day 3. He was discharged on postoperative day 4. A
      cystogram perfomed on postoperative day 7 revealed a good bladder capacity (350
      cc) and no leakage was identified. CONCLUSIONS: Robotic assisted partial
      cystectomy and urachal resection for urachal adenocarcinoma of the bladder is
      feasible even in challenging cases. This surgical approach is less morbid in
      terms of postoperative pain and cosmesis when compared to the open standard
      approach. The postoperative recovery is faster; however, application of
      oncological principles and comfort with laparoscopic and robotic surgery is
      needed prior to attempting such challenging cases. [Video - Available at:
      www.brazjurol.com.br/videos/september_october_2009/Spiess_609].

PMID- 19860962
TI  - EELS of niobium and stoichiometric niobium-oxide phases--Part I: plasmon and near
      edges fine structure.
AB  - A comprehensive electron energy-loss spectroscopy study of niobium (Nb) and
      stable Nb-oxide phases (NbO, NbO2, Nb2O5) was carried out. In this work (Part I),
      the plasmons and energy-loss near-edge structures (ELNES) of all relevant Nb
      edges (Nb-N2,3, Nb-M4,5, Nb-M2,3, Nb-M1, and Nb-L2,3) up to energy losses of
      about 2600 eV and the O-K edge are analyzed with respect to achieving
      characteristic fingerprints of Nb in different formal oxidation states (0 for
      metallic Nb, +2 for NbO, +4 for NbO2, and +5 for Nb2O5). Chemical shifts of the
      Nb-N2,3, Nb-M4,5, Nb-M2,3, and Nb-L2,3 edges are extracted from the spectra that
      amount to about 4 eV as the oxidation state increases from 0 for Nb to +5 for
      Nb2O5. Four different microscopes, including a 200 keV ZEISS Libra with
      monochromator, were used. The corresponding wide range of experimental parameters
      with respect to the primary electron energy, convergence, and collection semi
      angles as well as energy resolution allows an assessment of the influence of the
      experimental setup on the ELNES of the different edges. Finally, the intensity of
      the Nb-L2,3 white-line edges is correlated with niobium 4d-state occupancy in the
      different reference materials.

PMID- 19860963
TI  - [Memory controlled processes between the young and old: the birth of cognitive
      complaint?].
AB  - The aim of this study is to explore cognitive complaint by investigating the
      influence of memory controlled processes (recollection) and metacognitive
      beliefs. Several methodological precautions were taken in order to control
      neuropsychological and psychopathological criteria, like anxiety, depression or
      objective memory trouble. The "habit paradigm" (Hay & Jacoby, 1999) was used to
      create a "memory slips" task, and to estimate the contributions of recollection
      and habit to performance. Besides, participants were asked to complete
      questionnaires in order to assess cognitive complaint (CDS) and metacognitive
      beliefs (MCQ). Results showed that neither cognitive complaint nor metacognitive
      beliefs differed significantly between young and older persons. However,
      statistical analysis did show cognitive dissociations in function of cognitive
      complaint. Finally, depressive affects, memory controlled processes and
      metacognitive beliefs about the controllability of thoughts appeared as good
      predictors of memory complaint. In spite of our study limitations, we discuss our
      results in terms of clinical implications.

PMID- 19860964
TI  - Evaluation of a care pathway in the initiation of calcium and vitamin D treatment
      of patients after hip fracture.
AB  - Hip fractures, fragility fractures, indicate an increased risk for further
      fragility fractures. Although the way to define osteoporosis, requiring
      antiresorptive therapy, is not clear, all patients who have had hip fractures
      should be prescribed calcium and vitamin D at a minimum. In a retrospective chart
      review, we have explored the effectiveness of incorporating a standing
      recommendation (but not a standing order) for calcium and vitamin D treatment in
      a hip fracture care pathway, comparing units where the pathway had been
      implemented with those where it had not yet been started. The pathway resulted in
      significantly more initiation of calcium and vitamin D compared to patients not
      on the pathway (72% vs. 13.5%, p < 0.01). However, a follow-up study after four
      years showed a marked decline in the frequency of the initiation of calcium and
      vitamin D, suggesting the need for ongoing encouragement for the intervention to
      continue to be successful.

PMID- 19860965
TI  - [Do the activities of day programs for the elderly correspond to their various
      needs?].
AB  - This study was carried out to explore the fit between health and functional
      characteristics of Day Program participants and the types of program activities
      they were offered in Day Programs. The subjects were 132 participants from 5 Day
      Programs in Montreal. Four different participant profile groups were identified
      using cluster analysis. A classification of program activities was created by a
      panel of experts. Participation in these activities was studied for each profile
      group, and compared to recommended activities for such client groups outlined
      through examination of the literature and consultation with our panel of experts.
      Results showed only partial correspondence between program activities and
      participants' needs. This correspondence seemed higher for individuals with
      physical health problems or mobility impairments and weaker for those presenting
      depressive symptoms or cognitive impairments. These results suggest a need to
      review activity program components and determine ways to match better these with
      client needs to optimise the benefits of Day Program participation.

PMID- 19860966
TI  - Use of health services for psychological distress symptoms among community
      dwelling older adults.
AB  - ABSTRACTTo document the use of health services for psychological distress
      symptoms, we collected data from a cross-section of adults aged 65 years and
      over. Nearly 13 per cent met DSM-IV criteria for mood or anxiety disorders. In
      addition, 42.4 per cent of those having at least one DSM-IV diagnosis reported
      having used health services. Results show a direct association between the
      presence of a probable DSM-IV diagnosis and health service use. However, our
      results show no significant association between gender and health service use,
      and do not support the hypothesis that minimal social support increases the
      probability of older adults using health services for psychological distress. The
      analysis suggests unmarried elders are more likely than married elders to use
      health services. Furthermore, this study shows that older adults having a high
      level of daily hassles reported using health services for psychological distress
      than those reporting a low stress level. We conclude that a large proportion of
      elderly mental health needs in Quebec are potentially not being met.

PMID- 19860967
TI  - What is retirement? A review and assessment of alternative concepts and measures.
AB  - Because the concept of retirement is prominent in both popular thinking and
      academic studies, it would be helpful if the notion were analytically sound,
      could be measured with precision, and would make possible comparisons of patterns
      of retirement over time and among different populations. This paper reviews and
      assesses the many concepts and measures that have been proposed, summarizing them
      in groupings that reflect non-participation or reduced participation in the
      labour force, receipt of pension income, end-of-career employment, self-assessed
      retirement, or combinations of those characteristics. It concludes that there is
      no agreed measure and that no one measure dominates. Instead, new proposed
      measures continue to take account of additional refinements as new data sets
      become available, thereby further restricting possible comparisons. The confusing
      array of definitions reflects the practical problem that underlies the concept of
      retirement: It is an essentially negative notion, a notion of what people are not
      doing - namely, that they are not working. A more positive approach would be to
      focus, instead, on what people are doing, including especially their involvement
      in non-market activities that are socially productive, even if those activities
      do not contribute to national income as conventionally measured.

PMID- 19860968
TI  - Nurse practitioner and physician collaboration in long-term care homes: survey
      results.
AB  - This survey assessed the extent of and satisfaction with collaboration between
      physicians and nurse practitioners (NPs) working in Ontario long-term care homes.
      Questionnaires, which included the Measure of Current Collaboration and Provider
      Satisfaction with Current Collaboration instruments, were mailed to NPs and
      physicians with whom the NP most frequently worked. The 14 matched-pairs of NPs
      and physicians reported similar levels of collaboration; however, physicians were
      significantly more satisfied with collaboration than were NPs (z = -2.67, p =
      0.008). The majority of physicians (85%) and NPs (86%) indicated that
      collaboration was occurring, and 96 per cent of physicians and 79 per cent of NPs
      were satisfied with their collaboration. About one third of physicians reported
      that the NP had a negative effect on their income, but their satisfaction with
      collaboration did not differ from those who reported a positive effect. Overall,
      these physicians and NPs collaborate in delivering care and are satisfied with
      their collaboration.

PMID- 19860969
TI  - Developing a national consensus on the accessibility needs of older adults with
      concurrent and chronic, mental and physical health issues: a preliminary
      framework informing collaborative mental health care planning.
AB  - Canada faces a significant challenge in meeting the health care needs of older
      adults with complex mental and physical health issues. Studies have shown
      collaborative mental health services to effectively address the diverse health
      needs of this group. However, an often overlooked yet important aspect of service
      delivery planning for this population is to ensure that older adults are
      sufficiently able to access available best-practice services. The article reports
      on a national consensus-building exercise conducted by the Collaborative Mental
      Health Initiative-Seniors Working Group to develop a nationally informed
      framework on the accessibility needs of older adults as they relate to
      collaborative mental health care. The framework is intended to provide planners,
      administrators, and providers with an understanding of the unique accessibility
      needs of older adults across three priority pillars (personal, caregiver,
      systemic) and to enable them to embed strategies to address these issues within
      field-based collaborative mental health initiatives.

PMID- 19860970
TI  - Community-based home support agencies: comparing the quality of care of
      cooperative and non-profit organizations.
AB  - In the province of Quebec, services focusing on the instrumental activities of
      daily living are delivered to seniors by a combination of non-profit
      organizations and cooperatives. But do these organizations perform differently?
      This study asks whether home support cooperatives deliver higher-quality care
      than non-profit home support agencies. The specific effects of consumer and
      worker participation on the board of directors are also tested. Data were
      collected in 2006 and 2007 from 831 individuals receiving home support services
      from nine cooperatives and nine non-profits. Two consumer-centered measures of
      quality were used: a summated, 39-point satisfaction score and a 4-point overall
      quality score. Data were analyzed using ordered logistic regression. Results show
      that although organizational type was not a predictor of the two quality
      outcomes, worker involvement in governance was positively associated with the
      satisfaction score, while consumer involvement was positively associated with the
      overall quality score.

PMID- 19860971
TI  - [Development of an adapted leisure education program for persons with dementia].
AB  - Leisure represents a positive way to keep relationships satisfactory between
      caregivers and a person with dementia. Adapted leisure education is a promising
      approach to assist the family to discover new ways to share good times with their
      relatives. This study aimed to develop an adapted leisure education program. It
      included an evaluation of the caregivers' needs, the program content development,
      and a pilot study to experiment with the content of the program. Three focus
      groups of dementia caregivers (n = 19) were conducted to investigate caregivers
      needs. Based on content analysis of these focus groups and a literature review,
      the content of the program was developed. The pilot study (n = 4) included a
      quasi-experimental trial and an implementation evaluation. This study led to the
      development of an adapted leisure education program that puts caregiver support
      in a new perspective, focusing on positive aspects rather than the burden of
      caregiving.

PMID- 19860972
TI  - Gender role, life satisfaction, and wellness: androgyny in a southwestern Ontario
      sample.
AB  - This study investigated the relationships among gender role and self-reported
      health functioning in a sample of community dwelling older adults. One hundred
      and two (55 female, 47 male) participants were recruited through seniors'
      associations in Windsor, Ontario. Analyses of variance were conducted separately
      by gender to compare the self-rated physical health functioning, wellness, and
      life satisfaction of participants differing on classification of their gender
      role. For older women classified as androgynous, gender role exhibited
      significant effects on general wellness and life satisfaction, but not on self
      reported physical health functioning. In support of Bem's androgyny model of
      optimal adjustment, post-hoc analyses revealed that women who rated themselves as
      androgynous reported better overall wellness levels than their peers. Older men's
      self-reported physical health functioning and general wellness did not differ
      significantly by gender role. Limitations and implications are discussed.

PMID- 19860973
TI  - Personality and psychological health in persons with mild cognitive impairment.
AB  - An increasing number of studies have documented the cognitive profile of
      individuals with mild cognitive impairment (MCI), but few studies have
      investigated the individuals' psychological health and personality traits or how
      these factors interact with cognition. In the present study, 27 healthy older
      adults and 30 persons with MCI completed questionnaires covering psychological
      health, morale, personality, self-efficacy, and self-actualization. The results
      indicated that individuals with MCI are more depressed, anxious, hostile, and
      have lower morale than matched healthy older adults. Furthermore, our results
      show a positive association between the level of depression of MCI persons and
      the severity of their cognitive dysfunctions. In contrast, there were no group
      differences on measures of personality traits. Thus, while psychological distress
      is present in persons with MCI, those individuals are not characterized by
      differences in personality traits relative to older adults who experience no
      cognitive impairment.

PMID- 19860974
TI  - Fear of falling among elderly patients with dizziness and syncope in a tilt
      setting.
AB  - The objectives of this study were to assess the prevalence of fear of falling
      (FOF) among patients over age 60 with dizziness, falls, or syncope; and to
      analyze risk factors associated with FOF, including data from the tilt table
      test. This study included 200 older patients referred to a geriatric outpatient
      clinic specializing in dizziness, falls, and syncope. The primary outcome measure
      was the proportion of patients who experienced FOF (yes vs. no) and whether FOF
      restricted leaving home alone or performing activities of daily living. FOF
      occurred in 50 per cent of patients in this population. Among these, 44 per cent
      gave up going out alone and 10 per cent stopped doing basic activities of daily
      living. Beyond age 75, FOF was associated with recurrent dizziness, depression,
      and symptoms on standing, but not prior falls.

PMID- 19860975
TI  - The differential influence of culture change models on long-term care staff
      empowerment and provision of individualized care.
AB  - With this study we set out to determine if differences exist across culture
      change models (CCM) in relation to formal caregivers' perceived access to
      empowerment structures and reported provision of individualized care. We
      recruited staff working in facilities that had implemented the Eden Alternative,
      GentleCare, Facility Specific Social Models of Care (FSSMOC), or no CCM.
      Multivariate analyses of variance (MANOVA) compared these constructs by CCM for
      each of three caregiver groups (Registered Nurses, Licensed Practical Nurses, and
      care aides). Results suggest that considerable differences exist between formal
      caregivers and by CCM. The greater caregivers' day-to-day contact with residents,
      the more CCMs appear to affect perceived empowerment and reported provision of
      individualized care. Findings suggest the greatest benefits existed for staff
      working in facilities with a FSSMOC. Conversely, in only one instance did
      responses from staff in Eden Alternative facilities differ from those in
      facilities with no CCM.

PMID- 19860976
TI  - Exploring women's attitudes and intentions to seek care from nurse practitioners
      across different age groups.
AB  - Because public acceptance is critical for the successful integration of nurse
      practitioners into the Canadian health care system, the current study explored
      how women of different ages perceive nurse practitioners. Middle-aged women held
      more positive views of health care professionals in general and were more likely
      to indicate that they would seek help from nurse practitioners compared to
      younger and older women. Across all three age groups, respondents were more
      likely to seek help from physicians than from nurse practitioners, especially for
      acute (versus preventive) health concerns.

PMID- 19860977
TI  - The Canadian longitudinal study on aging (CLSA).
AB  - ABSTRACTCanadians are living longer, and older persons are making up a larger
      share of the population (14% in 2006, projected to rise to 20% by 2021). The
      Canadian Longitudinal Study on Aging (CLSA) is a national longitudinal study of
      adult development and aging that will recruit 50,000 Canadians aged 45 to 85
      years of age and follow them for at least 20 years. All participants will provide
      a common set of information concerning many aspects of health and aging, and
      30,000 will undergo an additional in-depth examination coupled with the donation
      of biological specimens (blood and urine). The CLSA will become a rich data
      source for the study of the complex interrelationship among the biological,
      physical, psychosocial, and societal factors that affect healthy aging.

PMID- 19860978
TI  - Exploring the acceptability and feasibility of conducting a large longitudinal
      population-based study in Canada.
AB  - ABSTRACTSuccessful recruitment and retention for population-based longitudinal
      studies requires understanding facilitators and barriers to participation. This
      study explored Canadians' views regarding one such study, the proposed Canadian
      Longitudinal Study on Aging (CLSA). Focus groups of participants > or =40 years
      of age were held in six proposed CLSA data collection sites (Halifax, Montreal,
      Hamilton, Winnipeg, Calgary, and Vancouver) to discuss participating in a long
      term study of healthy aging. There was fundamental support for longitudinal
      research on health and aging. Altruism was a key motivation to participation, and
      universities were viewed as credible parties to conduct such studies.
      Participants had few worries about providing biological samples but expressed
      concern about potential misuse of genetic materials, commercialization of
      participant data, and privacy issues. These findings have already informed
      current, and will inform future, work on the CLSA, and will also provide useful
      information to researchers who undertake other population-based longitudinal
      studies.

PMID- 19860979
TI  - The Canadian community health survey as a potential recruitment vehicle for the
      Canadian longitudinal study on aging.
AB  - ABSTRACTThe goal of the Canadian Longitudinal Study on Aging (CLSA) is to recruit
      50,000 participants aged 45 to 85 years of age and follow them for at least 20
      years. The sampling and recruitment processes for a study of this scope and
      magnitude present important challenges. Statistics Canada was approached to
      collaborate with the CLSA with the goal of determining whether the Canadian
      Community Health Survey (CCHS) could be used as a recruitment vehicle for the
      CLSA. In this pilot study conducted in 2004, it was determined that 63.8 per cent
      and 75.8 per cent of the respondents agreed to share their contact information
      and their survey responses with the CLSA, respectively. The most commonly
      reported concerns were confidentiality/privacy issues, lack of interest, and
      commitment issues. This pilot study identified some challenges to the use of the
      CCHS as a recruitment vehicle for the CLSA.

PMID- 19860980
TI  - Telephone-administered cognitive tests as tools for the identification of
      eligible study participants for population-based research in aging.
AB  - ABSTRACTAs part of its recruitment process, the Canadian Longitudinal Study on
      Aging (CLSA) will face the challenge of screening out individuals who are
      sufficiently impaired in their ability to provide informed consent. In the
      process of developing the design of the CLSA, a review of the literature was
      performed with the goal of identifying currently existing telephone cognitive
      screening tools that can be used to identify eligible study participants for
      population-based research on aging. We identified 12 telephone screening tools,
      four of which were based on the Mini-Mental State Exam (MMSE) and eight that were
      based on other face-to-face screening tools. Characteristics - including the
      constructs measured, the length of time for administration, the
      scoring/classification scheme, and any information regarding the validation of
      each tool - were extracted and summarized.

PMID- 19860981
TI  - Feasibility of biological specimen collection for the Canadian longitudinal study
      on aging (CLSA) biorepository.
AB  - ABSTRACTBiological specimen collection is an integral part of many longitudinal
      epidemiological studies. It is important to achieve high participant satisfaction
      for continuing involvement, and high sample quality for accurate biomarker
      measurement. We conducted a study to evaluate these issues on the sample
      collection proposed for the Canadian Longitudinal Study on Aging (CLSA). There
      were 85 participants recruited, and 65 attended either a hospital laboratory or
      private laboratory. Approximately 100 mL of blood and a random urine specimen
      were collected from each participant for a total of 2,108 sample aliquots.
      Quality standards were met for more than 90 per cent of samples and were similar
      for samples collected in both laboratories. More than 90 per cent of participants
      rated satisfaction with the collection as being good or excellent, and 84 per
      cent would be willing to repeat the collection in one to three years.

PMID- 19860982
TI  - Ascertainment of chronic diseases in the Canadian longitudinal study on aging
      (CLSA), systematic review.
AB  - ABSTRACTStandard clinical diagnostic procedures are often inappropriate and
      frequently not feasible to apply in population-based studies, yet ascertaining
      accurate disease status is essential. We conducted a systematic review to
      identify algorithms, criteria, and tools used to ascertain 17 chronic diseases,
      and assessed the feasibility of developing algorithms for the CLSA. Of the 29,616
      citations screened, 668 papers met all inclusion criteria. We determined that the
      information included in a disease algorithm will differ by condition type. The
      diagnosis of some symptomatic conditions, such as osteoarthritis and arthritis,
      will require substantiation by clinical criteria (e.g., x-rays, bone density
      measurement) while other conditions, such as depression, will rely solely on self
      report. Asymptomatic conditions, such as hypertension, are more difficult to
      ascertain by self-report and will require additional physiologic measures (e.g.,
      blood pressure) as well as laboratory measures (e.g., glucose). This pilot study
      identified the tools necessary to develop disease ascertainment algorithms.

PMID- 19860983
TI  - Accessing health care utilization databases for health research: a Canadian
      longitudinal study on aging feasibility study.
AB  - ABSTRACTOne of the keys to the success of the Canadian Longitudinal Study on
      Aging (CLSA) will be the leveraging of secondary data sources, particularly
      health care utilization (HCU) data. To examine the practical, methodological, and
      ethical aspects of accessing HCU data, one-on-one qualitative interviews were
      conducted with 53 data stewards and privacy commissioners/ombudsmen from across
      Canada. Study participants indicated that obtaining permission to access HCU data
      is generally possible; however, they noted that this will be a complex and
      lengthy process requiring considerable and meticulous preparatory work to ensure
      proper documentation and compliance with jurisdictional variations along
      legislative and policy lines.

PMID- 19860984
TI  - Effects of organically and conventionally produced feed on biomarkers of health
      in a chicken model.
AB  - Consumers expect organic products to be healthier. However, limited research has
      been performed to study the effect of organic food on health. The present study
      aimed to identify biomarkers of health to enable future studies in human
      subjects. A feeding experiment was performed in two generations of three groups
      of chickens differing in immune responsiveness, which were fed identically
      composed feeds from either organic or conventional produce. The animals of the
      second generation were exposed to an immune challenge and sacrificed at 13 weeks
      of age. Feed and ingredients were analysed on macro- and micronutrients, i.e.
      vitamins, minerals, trace elements, heavy metals and microbes. The chickens were
      studied by general health and immune parameters, metabolomics, genomics and post
      mortem evaluation. The organic and conventional feeds were comparable with
      respect to metabolisable energy. On average, the conventionally produced feeds
      had a 10 % higher protein content and some differences in micronutrients were
      observed. Although animals on both feeds were healthy, differences between the
      groups were found. The random control group of chickens fed conventional feed
      showed overall a higher weight gain during life span than the group on organic
      feed, although feed intake was mostly comparable. The animals on organic feed
      showed an enhanced immune reactivity, a stronger reaction to the immune challenge
      as well as a slightly stronger 'catch-up growth' after the challenge. Biomarkers
      for future research were identified in the parameters feed intake, body weight
      and growth rate, and in immunological, physiological and metabolic parameters,
      several of these differing most pronounced after the challenge.

PMID- 19860985
TI  - Effect of calcium on iron absorption in women with marginal iron status.
AB  - We measured non-haem Fe absorption with and without added Ca in a short-term
      feeding study, in thirteen women with marginal Fe status, by the use of a double
      stable isotope technique. Supplementing 500 mg Ca as calcium carbonate
      significantly (P = 0.0009) reduced Fe absorption from a single meal from 10.2 %
      (range 2.2-40.6) to 4.8 % (range 0.7-18.9). A significant inverse correlation in
      the absence ( - 0.67, P = 0.010) and presence ( - 0.58, P = 0.037) of Ca,
      respectively, was found between Fe absorption and Fe stores measured by serum
      ferritin (SF). Wide variation in Fe absorption was observed between individuals
      in the absence and in the presence of Ca, despite pre-selection of participants
      within a relatively narrow range of iron stores (SF concentrations). Correction
      of Fe absorption data based on group mean SF was not found to be useful in
      reducing the inter-individual variability in iron absorption. It appears that
      selecting a study group with a narrow initial range of Fe stores does not
      necessarily reduce the inter-individual variability in Fe bioavailability
      measurements. These results support the hypothesis that body Fe stores, although
      an important determinant of dietary Fe absorption, are not the main factor that
      determines Fe absorption under conditions of identical dietary intake in subjects
      with low Fe stores.

PMID- 19860986
TI  - Total parenteral nutrition in children and adolescents treated with high-dose
      chemotherapy followed by autologous haematopoietic transplants.
AB  - Total parenteral nutrition (TPN) is still of great importance for haematopoietic
      stem cell transplantation (HSCT) patients because one of the major adverse
      effects of the high-dose therapy followed by HSCT is an inadequate oral nutrition
      intake. The aim of the study was analysis of TPN of young patients in the HSCT
      period. Twenty-two patients 1.8-20.8 year-old, median 5.4, treated with high-dose
      therapy and autologous HSCT because of malignancy were included into the study.
      Grafts contained 1.35-7.9 x 106, median 3.75 x 106 CD34+ cells/kg. Engraftment
      occurred as follows: granulocytes >0.5 x 109/l on +11 d (8-25); platelets >20 x
      109/l on +23 d (12-67). Patients were given isoenergetic, isonitrogenous TPN
      until they consumed less than 50 % of their required diet orally. Proteins intake
      was 0.8-2.0 g/kg per d, fats intake 1.0-3.0 g/kg per d. Total non-proteins
      energies-nitrogen grams index was 140:1-200:1. Supplementation of electrolytes,
      microelements, trace elements and vitamins was dependent on individual patient
      requirement. TPN duration did not correlate with CD34+ cells number but
      correlated with platelets reconstitution. The assessment of nutritional condition
      demonstrated no differences in anthropometric parameters, but increase of serum
      albumin levels after TPN. Requirement for P3 - was above the normal ranges and
      correlated positively with platelets reconstitution. Requirement for P3 - and K+
      was higher in patients with mucositis than in other patients. Any complications
      due to TPN were observed. Adequately composed isoenergetic and isonitrogenous TPN
      with replacement of electrolytes according to their requirement in the early post
      transplantation period allows not only improvement in nutritional status of
      patients but also could contribute to reconstitution of haematopoiesis.

PMID- 19860987
TI  - Can Iberian red deer (Cervus elaphus hispanicus) discriminate among essential
      minerals in their diet?
AB  - Optimal foraging predicts that animals should be able to assess the content of
      important nutrients in food. Ungulates discriminate salt and P, but
      discrimination of other minerals is controversial even though they are also
      essential and often limiting. Animal scientists have explained this taste through
      palatability, which predicts the same pattern of discrimination for calves and
      hinds and greater consumption by the latter. Social learning may also be
      involved, predicting a correlation between mother and calf and less consumption
      by the latter. The present study examines the consumption behaviour of free
      choice supplemented minerals by hinds and calves of Iberian red deer (Cervus
      elaphus hispanicus) to discern between these hypotheses. Behavioural indices of
      intake correlated with actual mineral consumption (P < 0.001). Mother and calf
      behavioural indices correlated only for salt-mixed minerals. Calves showed
      overall behavioural indices of consumption greater than hinds (P < 0.01 and P <
      0.001), and also for all single supplements except NaCl, as expected from growth
      needs and in contrast to the palatability hypothesis. Calves showed a greater
      consumption of CuSO(4) and lower of Na(2)SeO(3) than pure salt. Hinds showed a
      different pattern, ingesting lower amounts of all minerals except CuSO(4) and
      salt. Additional analyses also showed discrimination between minerals unmixed
      with salt, such as CaHPO(4) and CaCO(3) (P = 0.012 and P = 0.020). The greater
      intake of growing calves and the different consumption patterns for hinds and
      calves suggest that deer can discriminate among minerals, and that they do not
      consume minerals for their palatability or driven by social learning. Therefore,
      deer may be selecting minerals according to nutritional requirements.

PMID- 19860988
TI  - Within-field damage and distribution patterns of the stalk borer, Eldana
      saccharina (Lepidoptera: Pyralidae), in sugarcane and a comparison with nematode
      damage.
AB  - The occurrence of Eldana saccharina (Lepidoptera: Pyralidae) was monitored in
      grids represented by plots in 12 nematicide trials in South African sugarcane
      fields. The trials encompassed a total of eight plant cane crops and 22 ratoon
      crops and were situated within commercial cane fields. Several measurements were
      made to characterize the damage caused by E. saccharina. These included the
      number of internodes per stalk, the percentage of internodes damaged and the
      percentage of stalks damaged. The mapping of E. saccharina infestation in plant
      crops of sugarcane showed that the borders of the trials were as infested as the
      centre, indicating invasion from outside the field plus internal spread within
      the field. Ratoon crops were less infested than plant crops. This could be
      explained by a shorter ratoon crop cycle and by the fields having areas that were
      more suitable for the borer than elsewhere. The location of these preferred areas
      could be predicted from one ratoon crop to the next but was not related to the
      distribution of the borer in the plant crop. This situation was thought to
      explain the apparent stabilization of E. saccharina infestation in ratoon cane.
      Because the borer was found at harvest only in stalks with more than 14 to 16
      internodes, it appeared that the oldest shoots, or the shoots with the greatest
      growth potential, attracted the insect, possibly due to their higher nitrogen
      content, which would stimulate growth. All the trials were on sandy soil, and
      crop loss from nematodes was greater than that caused by E. saccharina.

PMID- 19860989
TI  - Biology of eggs, embryos and larvae of Rhinelepis aspera (Spix & Agassiz, 1829)
      (Pisces: Siluriformes).
AB  - The black armoured catfish Rhinelepis aspera is an important commercial species
      found in the Sao Francisco River (Brazil) that has great potential for
      pisciculture. This paper presents, for the first time, information on the
      embryogenesis and larval development of this species. The breeder fish were
      subjected to spawning induction with crude carp pituitary extract. Eggs were kept
      in incubators at 24 degrees C and embryogenesis was observed with a
      stereomicroscope until hatching. Ovary fragments, samples of recently extruded
      oocytes and larvae were fixed in Bouin's solution and subjected to routine
      histology techniques. Recently extruded oocytes were also analyzed with a
      scanning electron microscope (SEM). Females (80%) had a positive response to
      hypophysation. Oocyte extrusion was performed at 8 h and 30 min after the second
      hormone injection and the fertilization rate achieved 72.4 +/- 8.8%. Recently
      extruded oocytes had a mean diameter of 1360.80 +/- 40.87 microm and presented a
      conspicuous jelly coat covering the zona pellucida. Histochemical reactions
      indicated the presence of neutral glycoproteins in the yolk globules and in the
      zona pellucida. These reactions also indicated the presence of neutral
      glycoproteins and carboxylated acid glycoconjugates in the follicular cells and
      the jelly coat. These compounds form mucosubstances that can be related to the
      adhesiveness of the eggs. Under the SEM the oocytes presented a micropyle disc
      and a thick jelly coat over their surface. The closure of the blastopore occurred
      9 h and 40 min after fertilization and embryogenesis was completed at 45 h and 50
      min after fertilization, when the embryos were incubated at 24 degrees C. The
      total absorption of the yolk sac occurred during the fifth day indicating the
      need for an exogenous food supply. These results provide essential information
      for the successful breeding and management of the promising R. aspera.

PMID- 19860990
TI  - Dietary intake and development of a quantitative FFQ for a nutritional
      intervention to reduce the risk of chronic disease in the Navajo Nation.
AB  - OBJECTIVES: To characterize dietary intake for Navajo adults, to identify foods
      for a nutritional intervention programme and to develop a culturally appropriate
      quantitative FFQ (QFFQ) for evaluating the impact of the intervention programme.
      DESIGN: A cross-sectional study was conducted using 24 h dietary recalls.
      SETTING: Navajo Nation, USA. SUBJECTS: Seventy-nine (forty men, thirty-nine
      women) aged 18-71 years completed 24 h dietary recalls. RESULTS: The median daily
      energy intake was 11 585 kJ (2769 kcal) for men and 8519 kJ (2036 kcal) for
      women. The greatest contributors to energy were fried potato dishes, sweetened
      juices/drinks, regular pop, bread, tortillas and burritos (contributing
      approximately 30 % of total energy intake). The mean number of meat servings was
      over twice that recommended (2-3 servings recommended v. 7.4 consumed by men and
      5.3 by women). The mean servings of vegetables were well below the recommendation
      of 3-5 servings (1.0 serving for men and 1.2 servings for women). The final QFFQ
      contains 177 food and drink items. CONCLUSIONS: Our study found that major
      contributors to total energy, fat and sugar intakes in the Navajo Nation included
      mostly processed meats and sweetened drinks. A nutritional intervention will
      target these foods and promote acceptable and healthier alternatives. In
      addition, we were able to identify foods and beverages for inclusion on a
      culturally appropriate QFFQ to assess dietary intake. This QFFQ will be used to
      evaluate the effectiveness of our intervention on food and food group consumption
      and nutrient intake.

PMID- 19860991
TI  - Policies that restrict sweetened beverage availability may reduce consumption in
      elementary-school children.
AB  - OBJECTIVE: We investigated whether having a policy regarding the availability of
      sweetened beverages in school was associated with children's purchase and total
      weekly and daily consumption of sweetened beverages. DESIGN: Data were obtained
      from 10 719 children aged 9-13 years and 2065 elementary schools in the Early
      Childhood Longitudinal Study-Kindergarten cohort. Multilevel logistic regression
      was used to determine the magnitude and significance of relationships between the
      availability of different beverages and purchase of sweetened beverages at school
      and overall consumption of beverages. RESULTS: The purchase of sweetened
      beverages by children in school was strongly associated with the administrative
      policy of sweetened beverage availability. Compared with children in schools
      without an administrative policy that allowed sweetened beverages, children in
      schools with the policy were three times more likely to be either occasional or
      frequent consumers of sweetened beverages. CONCLUSIONS: A policy of availability
      of sweetened beverages makes an independent contribution to children's purchase
      and consumption of sweetened beverages in the 5th grade year.

PMID- 19860992
TI  - Protection, promotion and support of breast-feeding in Europe: progress from 2002
      to 2007.
AB  - OBJECTIVE: To assess progress in the protection, promotion and support of breast
      feeding in Europe. DESIGN: Data for 2002 and 2007 were gathered with the same
      questionnaire. Of thirty countries, twenty-nine returned data for 2002, twenty
      four for 2007. RESULTS: The number of countries with national policies complying
      with WHO recommendations increased. In 2007, six countries lacked a national
      policy, three a national plan, four a national breast-feeding coordinator and
      committee. Little improvement was reported in pre-service training; however, the
      number of countries with good coverage in the provision of WHO/UNICEF courses for
      in-service training increased substantially, as reflected in a parallel increase
      in the number of Baby Friendly Hospitals and the proportion of births taking
      place in them. Little improvement was reported as far as implementation of the
      International Code on Marketing of Breastmilk Substitutes is concerned. Except
      for Ireland and the UK, where some improvement occurred, no changes were reported
      on maternity protection. Due to lack of standard methods, it was difficult to
      compare rates of breast-feeding among countries. With this in mind, slight
      improvements in the rates of initiation, exclusivity and duration were reported
      by countries where data at two points in time were available. CONCLUSIONS: Breast
      feeding rates continue to fall short of global recommendations. National policies
      are improving slowly but are hampered by the lack of action on maternity
      protection and the International Code. Pre-service training and standard
      monitoring of breast-feeding rates are the areas where more efforts are needed to
      accelerate progress.

PMID- 19860993
TI  - Long-term effectiveness and prediction of treatment outcome in cognitive
      behavioral therapy and sertraline for late-life anxiety disorders.
AB  - BACKGROUND: Although anxiety disorders are prevalent in older adults, randomized
      controlled trials of treatment effectiveness for late-life anxiety are scarce and
      have focused primarily on the effectiveness of psychotherapeutic interventions.
      However, recent findings suggest that in some cases, pharmacological treatment
      may be more beneficial for late-life anxiety disorders. As yet, there have been
      no systematic studies investigating prognostic factors for the outcome of
      cognitive behavioral therapy (CBT) and pharmacotherapy for late-life anxiety. The
      objective of the present study was to study long-term treatment outcomes and to
      explore differential predictors for both short-term and long-term treatment
      outcomes of sertraline and CBT for late-life anxiety disorders. METHODS:
      Participants of a randomized controlled trial (RCT) comparing sertraline and CBT
      for the treatment of late-life anxiety were contacted one year after completing
      their treatment, so that predictors for both short-term and long-term treatment
      outcome could be established. RESULTS: Sertraline showed a greater reduction of
      symptoms than CBT on anxiety (Hamilton Anxiety Rating Scale; HARS) and worry
      (Worry Domain Questionnaire) ratings at one-year follow-up. The strongest
      predictor for short-term CBT outcome was poor perceived health, explaining 40% of
      the variance in post-treatment residual gain scores on the HARS. The strongest
      predictor for long-term CBT outcome was neuroticism, explaining 20% of the
      variance in residual gain scores at one-year follow-up. Analyses revealed no
      significant predictors for treatment outcome in sertraline participants.
      CONCLUSIONS: Our study suggests that long-term use of sertraline might be more
      beneficial for late-life anxiety than a 15-week CBT program. Poor perceived
      health and neuroticism are predictive of less improvement after CBT in anxious
      older adults. Implications of these findings are discussed.

PMID- 19860994
TI  - Poor dietary quality of complementary foods is associated with multiple
      micronutrient deficiencies during early childhood in Mongolia.
AB  - OBJECTIVE: To assess whether persistent micronutrient deficiencies in Mongolian
      children identified in our earlier biochemical study are associated with
      inadequacies in quantity and/or quality in their complementary diets. DESIGN: A
      cross-sectional study of breast-fed children aged 6-23 months, randomly selected
      from four districts in Ulaanbaatar and four provincial capitals. SUBJECTS: Weight
      and length were measured, and sociodemographic status, feeding practices and
      nutrient adequacy of complementary foods for children aged 6-8 months (n 26), 9
      11 months (n 29) and 12-23 months (n 73) were assessed via questionnaire and in
      home interactive 24 h recalls. RESULTS: No geographic differences existed so data
      were combined. Adherence to WHO infant and young child feeding practices was
      poor: few children were exclusively breast-fed up to 6 months of age or received
      the recommended number of feedings containing the recommended number of food
      groups. Nevertheless, energy intakes from complementary diets, primarily from
      cereals and non-nutritious snacks, were above WHO-estimated needs; <1 % of energy
      was from meat and eggs or fruits and vegetables. Median intakes and densities of
      most nutrients (except protein, thiamin and riboflavin) failed to meet WHO
      recommendations for at least two age groups, assuming average breast milk intake;
      greatest density deficits were for Fe > vitamin C > vitamin A > Zn > Ca.
      CONCLUSIONS: Complementary feeding in Mongolia is compromised by deficits in
      several micronutrients but not energy, in part because of frequent consumption of
      non-nutritious snacks. The latter may interfere with breast-feeding and should be
      avoided. Instead, wheat-based complementary foods should be enriched with
      affordable cellular animal foods and fruits rich in vitamin C to combat existing
      micronutrient deficits.

PMID- 19860995
TI  - Iron intake and body iron stores, anaemia and risk of hyperglycaemia among
      Chinese adults: the prospective Jiangsu Nutrition Study (JIN).
AB  - OBJECTIVE: Fe supplementation has been used to prevent anaemia in China; however,
      high Fe intake and body Fe stores may increase diabetes risk. The present study
      aimed to prospectively examine the association between Fe intake/stores and
      hyperglycaemia, and to assess the joint effects on anaemia. DESIGN: We followed
      1056 healthy adults aged 20 years and older from 2002 to 2007. Body Fe stores
      were measured. Dietary data were collected using a 3 d food record and FFQ.
      Hyperglycaemia was defined as fasting plasma glucose >5.6 mmol/l. RESULTS: Of the
      participants, 28.8 % were anaemic at baseline. During the 5 years of follow-up,
      we documented 125 incident cases of hyperglycaemia, among them twenty-three were
      diabetic. Haem Fe intake was positively associated with the risk of
      hyperglycaemia in men and women: the OR (95 % CI) across increasing quartiles of
      haem Fe intake was 1.00 (referent), 1.49 (0.74, 3.01), 2.16 (1.06, 4.42) and 3.48
      (1.71, 7.11), respectively (P for trend <0.001). Comparing the fourth quartile of
      serum ferritin with the others, the age- and gender-adjusted OR (95 % CI) was
      1.54 (1.01, 2.34), P for trend = 0.043. The association between total Fe intake
      and the risk of hyperglycaemia was significant in men (P for trend = 0.002).
      Anaemia added additional risk of hyperglycaemia on haem Fe intake. Comparing
      extreme quartiles of haem Fe intake, the OR (95 % CI) was 5.67 (1.43, 22.49) and
      3.44 (1.51, 7.85) for hyperglycaemia among anaemic and non-anaemic participants
      (P for trend = 0.008 and 0.010, respectively). CONCLUSIONS: The present cohort
      study suggests that high haem Fe intake, anaemia and high ferritin are associated
      with an increased risk of hyperglycaemia in Chinese men and women. There was a
      joint effect between anaemia and haem Fe intake on the risk of hyperglycaemia.

PMID- 19860996
TI  - Differential effects of dietary fatty acids on the cerebral distribution of
      plasma-derived apo B lipoproteins with amyloid-beta.
AB  - Some dietary fats are a risk factor for Alzheimer's disease (AD) but the
      mechanisms for this association are presently unknown. In the present study we
      showed in wild-type mice that chronic ingestion of SFA results in blood-brain
      barrier (BBB) dysfunction and significant delivery into the brain of plasma
      proteins, including apo B lipoproteins that are endogenously enriched in amyloid
      beta (Abeta). Conversely, the plasma concentration of S100B was used as a marker
      of brain-to-blood leakage and was found to be increased two-fold because of SFA
      feeding. Consistent with a deterioration in BBB integrity in SFA-fed mice was a
      diminished cerebrovascular expression of occludin, an endothelial tight junction
      protein. In contrast to SFA-fed mice, chronic ingestion of MUFA or PUFA had no
      detrimental effect on BBB integrity. Utilising highly sensitive three-dimensional
      immunomicroscopy, we also showed that the cerebral distribution and co
      localisation of Abeta with apo B lipoproteins in SFA-fed mice are similar to
      those found in amyloid precursor protein/presenilin-1 (APP/PS1) amyloid
      transgenic mice, an established murine model of AD. Moreover, there was a strong
      positive association of plasma-derived apo B lipoproteins with cerebral Abeta
      deposits. Collectively, the findings of the present study provide a plausible
      explanation of how dietary fats may influence AD risk. Ingestion of SFA could
      enhance peripheral delivery to the brain of circulating lipoprotein-Abeta and
      exacerbate the amyloidogenic cascade.

PMID- 19860998
TI  - Epidemiology of vitamin D in health and disease.
AB  - Results from ecological, case-control and cohort studies have shown that vitamin
      D reduces the risk of bone fracture, falls, autoimmune diseases, type 2 diabetes,
      CVD and cancer. However, there is still epidemic vitamin D insufficiency
      especially among individuals living at high latitudes or with dark skin. Serum
      levels of 25-hydroxyvitamin D (25(OH)D) are considered the best biomarker of
      vitamin D nutritional status. Appropriate sunshine exposure or oral
      supplementation is necessary to maintain sufficient vitamin D status, which is
      generally accepted as serum 25(OH)D>75 nmol/l. Immunoassays, especially RIA, have
      been primarily used to measure serum 25(OH)D while liquid chromatography-MS (LC
      MS) is considered the 'gold standard'. There is significant disparity among the
      immunoassays, and all immunoassays have considerable bias compared with LC-MS
      methods. Because of the variations among the results from these different assays,
      it is necessary that assay-specific reference ranges be established or
      standardisation of the assays take place. The present review focuses on
      ecological, case-control, and cohort studies that investigated the role of
      vitamin D in health and disease. In addition, analytical techniques used in
      laboratory evaluation of vitamin D nutritional status are also critically
      reviewed. The majority of the literature included in the present review is
      selected from that searchable in PubMed up to the end of September 2008.

PMID- 19860999
TI  - Who speaks for the children?

PMID- 19860997
TI  - Midkine expression is regulated by the circadian clock in the retina of the
      zebrafish.
AB  - The retina displays numerous processes that follow a circadian rhythm. These
      processes are coordinated through the direct action of light on photoreceptive
      molecules and, in the absence of light, through autocrine/paracrine actions of
      extracellular neuromodulators. We previously described the expression of the
      genes encoding the secreted heparin-binding growth factors, midkine-a (mdka) and
      midkine-b (mdkb), in the retina of the zebrafish. Here, we provide evidence that
      the expression of mdka and mdkb follows a daily rhythm, which is independent of
      the presence or absence of light, and we propose that the expression of mdka is
      regulated by the circadian clock. Both qualitative and quantitative measures show
      that for mdka, the levels of mRNA and protein decrease during the night and
      increase during the subjective day. Qualitative measures show that the expression
      of mdkb increases during the second half of the subjective night and decreases
      during the second half of the subjective day. Within horizontal cells, the two
      midkine paralogs show asynchronous circadian regulation. Though intensely studied
      in the contexts of physiology and disease, this is the first study to provide
      evidence for the circadian regulation of midkines in the vertebrate nervous
      system.

PMID- 19861000
TI  - Pneumonia prevention gets a fresh opportunity.

PMID- 19861001
TI  - State of the Art series on drug-resistant tuberculosis: it's time to protect
      fluoroquinolones.

PMID- 19861002
TI  - Mechanisms of drug resistance in Mycobacterium tuberculosis.
AB  - The increasing emergence of multidrug-resistant (MDR) and extensively drug
      resistant (XDR) tuberculosis (TB) in the era of human immunodeficiency virus
      (HIV) infection presents a major threat to effective control of TB. Drug
      resistance in Mycobacterium tuberculosis arises from spontaneous chromosomal
      mutations at low frequency. Clinical drug-resistant TB largely occurs as a result
      of man-made selection during disease treatment of these genetic alterations
      through erratic drug supply, suboptimal physician prescription and poor patient
      adherence. Molecular mechanisms of drug resistance have been elucidated for the
      major first- and second-line drugs rifampicin, isoniazid, pyrazinamide,
      ethambutol, the aminoglycosides and the fluoroquinolones. The relationship
      between drug resistance in M. tuberculosis strains and their
      virulence/transmissibility needs to be further investigated. Understanding the
      mechanisms of drug resistance in M. tuberculosis would enable the development of
      rapid molecular diagnostic tools and furnish possible insights into new drug
      development for the treatment of TB.

PMID- 19861003
TI  - Bacille Calmette-Guerin vaccine-related disease in HIV-infected children: a
      systematic review.
AB  - OBJECTIVE: To describe the characteristics and risk of bacille Calmette-Guerin
      (BCG) vaccine related disease in human immunodeficiency virus (HIV) infected
      infants. METHODS: Systematic literature review of articles published from 1950 to
      April 2009 in the English language. We identified all microbiologically confirmed
      cases of disseminated BCG disease in vertically HIV-infected children reported in
      the literature. RESULTS: Sixteen observational studies and 11 case reports/series
      were included. Observational studies suffered from high rates of loss to follow
      up and death. Loco-regional BCG disease was reported in both HIV-infected and non
      infected children. Disseminated BCG disease was reported only in children with
      immunodeficiency and only in studies employing sophisticated laboratory
      techniques. Sixty-nine cases of disseminated BCG were identified in the
      literature: 47 cases were reported in six observational studies, the majority
      (41/47) from the Western Cape of South Africa. A Brazilian cohort study reported
      no cases of disseminated BCG amongst 66 HIV-infected children observed over a 7
      year period. A recent South African surveillance study reported 32 cases of
      disseminated BCG over a 3-year period, estimating the risk of disseminated BCG to
      be 992 per 100,000 vaccinations in HIV-infected children. Few cases of severe
      disseminated TB were reported in the cohort studies among HIV-infected children
      vaccinated with BCG. CONCLUSION: Data on the risk of BCG vaccination in HIV
      infected children are limited. Targeted surveillance for BCG complications
      employing sophisticated diagnostic techniques is required to inform vaccination
      policy.

PMID- 19861004
TI  - Wade Hampton Frost and the index case concept.

PMID- 19861005
TI  - First documentation of isoniazid reversion in Mycobacterium tuberculosis.
AB  - BACKGROUND: Drug-resistant strains of Mycobacterium tuberculosis are increasing
      worldwide and pose a major threat to global health. However, it remains unsettled
      whether drug-resistant mutants are fixed in the bacterial population or if they
      would revert in the absence of drug pressure. OBJECTIVE: To document the
      occurrence of isoniazid (INH) reversion in a patient with multidrug-resistant
      tuberculosis (TB) and investigate its association with fitness cost. DESIGN:
      Genotypic and phenotypic assays were used to characterize the reversion of INH
      resistance in isolates from a patient with pulmonary TB. The pre-reversion katG
      mutation was reconstructed in a pan-susceptible laboratory strain (H37Rv
      DeltakatG::katG W300G) and tested for susceptibility to INH and oxidative stress.
      RESULTS: Genotyping and drug susceptibility testing showed that an isogenic
      strain of M. tuberculosis reverted from an INH-resistant to a susceptible
      phenotype in the absence of INH therapy. The genotypic basis of this reversion
      was mapped to the katG codon 300 which reverted from GGG (glycine, G) to a wild
      type codon, TGG (tryptophan, W). The H37Rv DeltakatG::katG W300G mutant was
      resistant to INH, but also showed a deficiency in coping with oxidative stress.
      CONCLUSION: This study confirms that, in the absence of INH pressure, some INH
      resistant mutants will revert to a drug-susceptible phenotype. This finding may
      have broader implications for INH-resistant strains and for the clinically useful
      lifespan of INH.

PMID- 19861006
TI  - Ethionamide cross- and co-resistance in children with isoniazid-resistant
      tuberculosis.
AB  - BACKGROUND: Ethionamide (ETH) is a structural analogue of isoniazid (INH). Both
      are pro-drugs requiring activation by separate and common enzyme pathways, which
      could lead to co- and/or cross-resistance. OBJECTIVE: To characterise paediatric
      INH-resistant mycobacterial isolates to investigate the presence of ETH
      resistance and mutations in the katG gene and the inhA promoter region. METHODS:
      Forty-five INH-resistant and 19 INH-susceptible Mycobacterium tuberculosis
      control isolates from children from the Western Cape Province, South Africa, were
      analysed to quantify INH minimal inhibitory concentration, test for ETH
      resistance and investigate mutations in the katG gene and/or inhA promoter
      region. RESULTS: Among 45 INH-resistant children, ETH resistance was present in
      19 of 39 (49%). An inhA promoter mutation was identified in 15 (33.3%); 12/14
      (86%) of these isolates were also ETH-resistant. Of the 21 isolates with a katG
      mutation, six (29%) were ETH-resistant. No isolate had both katG and inhA
      promoter mutations. Nine (20%) isolates had neither inhA promoter nor katG
      mutations. Of 15 isolates with inhA promoter mutation, 14 (93%) displayed low- or
      intermediate-level INH resistance. Among the 19 INH-susceptible isolates, ETH
      resistance was present in 1/18 (6%) and none showed inhA or katG gene mutations.
      CONCLUSION: We found a high level of cross- and co-resistance with ETH among INH
      resistant M. tuberculosis isolates from children in this geographic area.

PMID- 19861008
TI  - Assessment of global capacity to conduct tuberculosis drug development trials: do
      we have what it takes?
AB  - OBJECTIVE: To assess clinical trial sites and associated mycobacteriology
      laboratories for their capacity to conduct registration-standard tuberculosis
      (TB) drug trials and develop a database of assessed sites and laboratories.
      SETTING: Assessments of clinical trial sites and associated mycobacteriology
      laboratories were conducted in 39 countries from 2006 to 2008. DESIGN: Sites were
      interviewed using a set of questionnaires to assess the clinical site, pharmacy,
      data management, regulatory, ethics and importation requirements and
      mycobacteriology laboratory. Each site and laboratory was rated as able to
      conduct TB drug registration trials within 0-6 months, >6-12 months, >1-2 years
      and >2 years. RESULTS: Eighty-four clinical trial sites and associated
      mycobacteriology laboratories in 39 countries were assessed. Of the clinical
      trial sites, 50% were judged capable of being ready within 6 months, 32.1% in 6
      12 months and 14.3% in 1-2 years. Three sites would be ready in more than 2
      years. Of the 72 mycobacteriology laboratories, 27.8% could be made ready within
      6 months, 37.5% within 6-12 months and 27.8% within 1-2 years. CONCLUSION: This
      survey indicates that developing adequate capacity to fully evaluate the
      compounds now in the clinical phases of development will require significant
      capacity-building efforts.

PMID- 19861007
TI  - GLS/IL-12-modified Mycobacterium smegmatis as a novel anti-tuberculosis
      immunotherapeutic vaccine.
AB  - OBJECTIVE: To study the effects and mechanisms of recombinant Mycobacterium
      smegmatis (rMS) carrying pZM03 (a co-expression plasmid encoding human granulysin
      [GLS] and murine interleukin 12 [IL-12]) on murine M. tuberculosis infection.
      DESIGN: BALB/c mice infected with M. tuberculosis were treated with normal
      saline, M. smegmatis, pZM03 or rMS. The number of viable bacteria in the lungs
      and spleens were counted to observe the therapeutic effects. The levels of IL-12
      and interferon-gamma (IFN-gamma) in serum, and IFN-gamma and tumour necrosis
      factor-alpha (TNF-alpha) released from spleen lymphocytes were detected to
      observe the T-helper 1 (Th1) response. Secretory IgA (SIgA) in bronchoalveolar
      lavage fluid was measured to observe the mucosal immunity. The lungs and spleens
      were prepared for pathological analysis. RESULTS: The rMS group showed a
      significantly reduced number of colony-forming units compared to the other
      groups. The expression of GLS in the tissue, and increased levels of IL-12, IFN
      gamma, TNF-alpha and SIgA, were found in the rMS group. The pathological changes
      in the lungs of the rMS group were localised, while those in the control group
      were extensive. CONCLUSION: rMS had immunotherapeutic effects associated with a
      switch to the Th1 response and the antibacterial activity of GLS.

PMID- 19861009
TI  - Fine-needle aspiration biopsy: a first-line diagnostic procedure in paediatric
      tuberculosis suspects with peripheral lymphadenopathy?
AB  - OBJECTIVE: To evaluate the diagnostic yield and time to diagnosis of fine-needle
      aspiration biopsy (FNAB) vs. routine respiratory specimens collected from
      children with a palpable peripheral lymph node mass and symptoms suspicious of
      tuberculosis (TB). DESIGN: We performed a retrospective review of laboratory
      records at Tygerberg Hospital over a 4-year period from January 2003 to December
      2006. All children (aged <13 years) in whom an FNAB and other mycobacterial
      specimens were collected as part of their diagnostic workup were included.
      RESULTS: In 95 children, the following specimens were collected: FNAB (n = 95),
      gastric aspirates (n = 142), other respiratory specimens (n = 36), non
      respiratory specimens (n = 26). Mycobacterial disease was diagnosed in 70 (73.7%)
      patients. Children without respiratory specimens (n = 6) and/or with
      Mycobacterium bovis bacille Calmette-Guerin disease (n = 15) were excluded from
      comparative analysis. In the remainder, FNAB was positive in 45/74 (60.8%) vs.
      any respiratory specimen in 29/74 (39.2%, P < 0.001). The mean time to
      bacteriological diagnosis with FNAB was 7.1 days (95%CI 4.2-10.1) compared to
      22.5 days (95%CI 15.8-29.1) for any respiratory specimen. CONCLUSION: FNAB is a
      simple, rapid and effective modality for achieving confirmation of mycobacterial
      disease in paediatric TB suspects with a palpable peripheral lymph node mass.

PMID- 19861010
TI  - The role of chest radiography in the suspicion for and diagnosis of pulmonary
      tuberculosis in intensive care units.
AB  - BACKGROUND: The role of chest radiography (CXR) in the clinical diagnosis and
      suspicion of pulmonary tuberculosis (PTB) remains uncertain in the intensive care
      unit (ICU) setting. DESIGN: This case-control study compared the radiographic
      findings between ICU patients with and without co-existing PTB to define any
      predictive patterns for the diagnosis of PTB. Further analysis aimed to elucidate
      the impact of CXR on the clinical suspicion of PTB. RESULTS: Eighty-nine (89)
      patients with PTB and an equal number of matched controls were evaluated.
      Consolidation was the most frequent radiographic pattern. There were no specific
      predictors for diagnosing PTB in the ICU. Of 89 patients, 55 (62.9%) had a delay
      in clinical suspicion of PTB. The time from ICU admission to TB diagnosis was
      significantly delayed in the group without clinical suspicion (30.7 vs. 5.3 days,
      P < 0.001). In multivariate analysis, a history of PTB was significantly
      associated with the clinical suspicion of PTB (OR 7.94, P = 0.012), but CXR
      patterns were not. CONCLUSION: CXR does not contribute as much as expected in the
      clinical diagnosis and suspicion of PTB in the ICU setting.

PMID- 19861011
TI  - Radiological presentation of pulmonary tuberculosis infected by the W-Beijing
      Mycobacterium tuberculosis strain.
AB  - SETTING: The W-Beijing strain of Mycobacterium tuberculosis is distributed
      globally, and is associated with high drug resistance rates in some areas. The
      effect of the W-Beijing strain on radiological features of pulmonary tuberculosis
      (PTB) remains unclear. OBJECTIVE: To compare the chest radiological presentation
      of PTB in patients infected with W-Beijing with that of patients infected with
      non-W-Beijing strains, and to explore factors affecting radiological patterns.
      DESIGN: Culture-proven PTB patients without previous anti-tuberculosis treatment
      were enrolled retrospectively. Chest radiographs were independently reviewed by
      two qualified chest physicians, and radiological presentation was classified into
      characteristic and unusual patterns. RESULTS: Of 233 patients studied, 123
      (52.8%) were infected with the W-Beijing strain. Characteristic radiological
      patterns (91.1% vs. 76.4%, P = 0.002) and fibronodular lesions without cavity
      (57.7% vs. 43.6%, P = 0.032) were more common, while miliary lesions (0.0% vs.
      3.8%, P = 0.048) were less frequent, in the W-Beijing group. After stepwise
      logistic regression analysis, the W-Beijing strain (P = 0.006) was found to be an
      independent factor for the characteristic radiological pattern for PTB.
      CONCLUSION: The characteristic radiological pattern for PTB was more common in
      patients infected with the W-Beijing strain. M. tuberculosis genotyping was an
      independent factor affecting the radiological presentation of pulmonary TB.

PMID- 19861012
TI  - Quantitative differences in sputum smear microscopy results for acid-fast bacilli
      by age and sex in four countries.
AB  - OBJECTIVE: To examine the influence of age and sex on the grading of tuberculosis
      (TB) sputum smear microscopy results. SETTING: Laboratories in Moldova, Mongolia,
      Uganda and Zimbabwe. METHODS: Data from nationally representative samples of
      laboratory registers were double-entered and validated, and discordances were
      resolved by rechecking against the registers. RESULTS: The dataset comprised
      128,808 examinees from 23 laboratories in Moldova, all 31 in Mongolia, 30 in
      Uganda and 23 in Zimbabwe, each covering at least one calendar year. Among all
      examinees, 89,362 had a diagnostic examination, 13,577 (15.2%) of whom were
      cases. A non-quantified positive result was recorded among 1272 (9.4%) of these.
      Scanty results were most frequent in Zimbabwe (8.5%) and most infrequent in
      Uganda (1.1%). In contrast, the highest grade, of 3+ positive, was most frequent
      (43.9%) in Mongolia. The lowest proportion of low-grade positivity was recorded
      for males aged 15-24 years and the highest among females aged >or=65 years.
      CONCLUSION: Differences in the frequency of low-grade positivity between the four
      countries were striking. Females tended to have lower bacillary counts, and low
      grade positivity was more frequent at the extremes of age. These results
      reinforce the need for appropriate instructions on how to produce high-quality
      sputum to improve yield.

PMID- 19861013
TI  - Evaluating an active case-finding strategy to identify smear-positive
      tuberculosis in rural Ethiopia.
AB  - OBJECTIVE: To assess an active case-finding strategy for the identification of
      smear-positive pulmonary tuberculosis (TB) in a rural district of Amhara Region,
      Ethiopia. METHODS: Study kebeles (smallest administrative units) were randomly
      selected in a cross-sectional study. House-to-house visits involving individuals
      aged >or=15 years in all households of the kebeles were conducted. The heads of
      households were asked to identify subjects with TB symptoms. Identified suspects
      were asked to provide three sputum samples for smear microscopy. RESULTS: Among
      the 47,478 individuals living in households that were screened, 1006 TB suspects
      and 38 cases were detected. This resulted in 38 cases of smear-positive TB, i.e.,
      80 per 100,000 population, using cluster sampling. The ratio of active vs.
      passive case detection was 2.5:1, indicating 2.5 undetected TB cases in the
      community for every smear-positive TB case receiving treatment during the survey
      period. A higher proportion of female patients was detected by the survey.
      CONCLUSION: The study revealed a very high proportion of undiagnosed TB. This
      indicates that the potential for a large infectious pool and significant
      transmission of TB in the community is high. The expansion of diagnostic
      facilities and the active involvement of health extension workers is necessary to
      expedite early detection, timely referral and treatment of TB.

PMID- 19861014
TI  - Drug prescribing practices for tuberculosis in Uzbekistan.
AB  - SETTING: Uzbekistan has had 100% DOTS coverage since 2005; however, the treatment
      success rate has remained at around 80% for the last 4 years. Surveys from the
      capital city of Tashkent and from western Uzbekistan have shown high levels of
      primary multidrug resistance. OBJECTIVE: To assess treatment regimens prescribed
      for new cases of tuberculosis (TB), including the prescription of additional non
      TB drugs, and the cost implications for the patient. DESIGN: We randomly sampled
      30 clusters of seven new TB patients. Enrolled patients were interviewed and
      their medical records were reviewed. RESULTS: In general, the treatment regimens
      prescribed were correct; doses were high rather than low. Second-line anti
      tuberculosis drugs were rarely prescribed. In addition to anti-tuberculosis
      drugs, patients were prescribed on average seven to eight non-TB drugs. The
      rationale for prescribing the non-TB drugs was, however, questionable. Patients
      incurred substantial costs for these drugs, some of which were not without risk.
      CONCLUSION: Prescriptions of anti-tuberculosis drugs for new TB patients are
      adequate; however, the practice of prescribing additional non-TB drugs needs to
      be reconsidered.

PMID- 19861015
TI  - Interferon-gamma release assay test characteristics depend upon the prevalence of
      active tuberculosis.
AB  - BACKGROUND: Tuberculin skin tests (TSTs) may be negative in the absence of latent
      tuberculosis infection (LTBI) or in the presence of active tuberculosis (TB). The
      same phenomenon likely holds for interferon-gamma release assays (IGRAs).
      METHODS: A mathematical model of LTBI test specificity was developed using
      elementary probability theory. Implications for IGRA study design, and data
      collection and analysis are presented. RESULTS: The model demonstrates that the
      specificity of any test for LTBI is theoretically affected by its sensitivity to
      active TB, and by the distribution of TB, LTBI and healthy controls. Moreover,
      changing cut-off points to increase the sensitivity for active TB will cause a
      decline in the specificity for LTBI. Published data are used to demonstrate these
      counterintuitive results. CONCLUSIONS: As a result of the markedly dissimilar
      health statuses associated with a negative LTBI test, IGRA specificity for LTBI
      and sensitivity to active TB depend upon TB and LTBI prevalence. A trade-off
      exists between the specificity of IGRAs to LTBI and sensitivity to active TB.
      Field studies of IGRAs will require standardized collection of symptoms of active
      TB to distinguish LTBI suspects from TB suspects. Different cut-off points for
      IGRA use in TB suspects and LTBI suspects will likely be needed.

PMID- 19861016
TI  - Evaluation of an interferon-gamma release assay, T-SPOT.TB, in a population with
      a low prevalence of tuberculosis.
AB  - SETTING: Great Lakes, Illinois, USA. OBJECTIVE: To compare the performance of an
      interferon-gamma release assay (T-SPOT.TB) and tuberculin skin test (TST) in a
      population with a low prevalence of tuberculosis (TB) that was predominantly US
      born and not bacille Calmette-Guerin-vaccinated. DESIGN: A total of 414 subjects
      with absence of a previous positive TST were enrolled, of whom 326 yielded
      analyzable results for both TST and T-SPOT.TB. RESULTS: Overall agreement between
      T-SPOT.TB and TST was 98.2% (95%CI 96.0-99.3). The specificity of T-SPOT.TB in
      individuals judged to be at low risk for TB infection was 98.9% (95%CI 96.9
      99.8). Of 326 subjects, 8 (2.5%) had a positive T-SPOT.TB result, six of which
      occurred in the absence of a positive TST. Of these, at least three appeared to
      have risk factors, suggesting the possibility of a false-negative TST result.
      CONCLUSION: Because of the excellent agreement between the TSPOT.TB and the TST,
      either test can serve as an effective diagnostic tool in populations at low risk
      for TB. As the tests have specific advantages and disadvantages, health care
      providers have leeway in choosing the most appropriate test for the population
      they are treating.

PMID- 19861017
TI  - Clinical evaluation of the QuantiFERON-TB Gold test in patients with non
      tuberculous mycobacterial disease.
AB  - OBJECTIVE: To evaluate the clinical usefulness of the QuantiFERON TB-2G (QFT-2G)
      test in patients with non-tuberculous mycobacterial (NTM) disease without a
      previous history of tuberculosis (TB). METHODS: The study consisted of 214
      patients with NTM disease who satisfied the diagnostic guidelines of the American
      Thoracic Society. RESULTS: The causative microorganism was Mycobacterium avium in
      83 patients, M. intracellulare in 80, M. kansasii in 33, M. marinum in 12, M.
      szulgai in 3, M. abscessus in 2 and M. chelonei in 1. The positive response rate
      of QFT-2G test result was 2% in 163 patients with M. avium-intracellulare complex
      (MAIC) disease, 52% in 33 with M. kansasii disease, 58% in 12 with M. marinum
      disease, 33% in 3 with M. szulgai disease, 0% in two with M. abscessus disease
      and 0% in one with M. chelonei disease. The positivity of the QFT-2G test was 52%
      in patients with NTM disease, thought to be because NTM possesses common M.
      tuberculosis-specific antigens. CONCLUSIONS: Although QFT-2G may be a useful
      diagnostic method to differentiate TB from MAIC disease, there are several
      problems to be resolved before it can be used as a diagnostic method for NTM
      disease (M. kansasii disease), including the determination of the positive cut
      off level for QFT-2G test.

PMID- 19861018
TI  - QuantiFERON-TB Gold in the identification of latent tuberculosis infection in
      rheumatoid arthritis: a pilot study.
AB  - OBJECTIVE: To compare the performance of QuantiFERON-TB Gold (QFT-G) with that of
      the tuberculin skin test (TST) in detecting latent tuberculosis (LTBI) among
      patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 35 RA
      patients and 15 healthy controls underwent TST, QFT-G assays and chest X-ray and
      filled out a questionnaire on predisposing conditions for TB disease. Serum
      interferon gamma (IFN-gamma) levels were tested by an enzyme-linked immunosorbent
      assay. RESULTS: Forty-five per cent of RA patients had a TST > 5 mm vs. 26% in
      healthy controls. In the RA patients, QFT-G was positive in 11.4%, negative in
      60% and indeterminate in 28.6%. The overall agreement between TST and QFT-G was
      significantly lower in the RA population than in controls (56% vs. 84%). No
      correlation was found between the use of prednisone, methotrexate and QFT-G
      results or agreement between TST and QFT-G. A low IFN-gamma level (<4 pg/ml) was
      found in 51.5% of the RA patients. No correlation was found between serum IFN
      gamma levels and QFT-G results. CONCLUSION: The clinical significance of negative
      QFT-G in TST-positive patients with low TB risk remains to be assessed. The high
      rate of indeterminate results questions the clinical utility of QFT-G in the
      diagnosis of LTBI in RA patients.

PMID- 19861019
TI  - Tobacco use and its determinants in HIV-infected patients on antiretroviral
      therapy in West African countries.
AB  - BACKGROUND: Tobacco smoking is common in human immunodeficiency virus (HIV)
      infected patients from industrialised countries. In West Africa, few data
      concerning tobacco consumption exist. METHODS: A cross-sectional survey of the
      International Epidemiological Database to Evaluate AIDS (IeDEA) network in West
      Africa was conducted. Health workers administered a questionnaire assessing
      tobacco and cannabis consumption among patients receiving antiretroviral
      treatment. Regular smokers were defined as current smokers who smoked >1
      cigarette per day for >or=1 year. RESULTS: Overall, 2920 patients were enrolled
      in three countries. The prevalence of ever smokers and regular smokers were
      respectively 46.2% (95%CI 42.8-49.5) and 15.6% (95%CI 13.2-18.0) in men and 3.7%
      (95%CI 2.9-4.5) and 0.6% (95%CI 0.3-0.9) in women. Regular smoking was associated
      with being from Cote d'Ivoire or Mali compared to Benin (OR 4.6, 95%CI 2.9-7.3
      and 7.7, 95%CI 4.4-13.6), severely impaired immunological status at highly active
      antiretroviral treatment initiation (OR 1.5, 95%CI 1.1-2.2) and history of
      tuberculosis (TB; OR 1.8, 95%CI 1.1-3.0). CONCLUSION: There are marked
      differences in smoking prevalence among these West African countries. This survey
      approach also provides proof of the association between cigarette smoking and TB
      in HIV-infected patients, a major public health issue in this part of the world.

PMID- 19861020
TI  - Molecular characterisation of rifampicin-resistant Mycobacterium tuberculosis
      strains from Morocco.
AB  - Mutations in the rpoB gene associated with rifampicin (RMP) resistance were
      studied in 47 RMP-resistant and 147 RMP-susceptible clinical strains of
      Mycobacterium tuberculosis from Morocco using probe-based assay and DNA
      sequencing. RMP-resistant mutations were identified in 85% of RMP-resistant
      isolates. No mutations were observed among the 147 RMP-susceptible strains.
      Sequence analysis identified 10 alleles, including two deletions not previously
      reported. Nucleotide changes at codons 531, 526 and 516 were the most prominent,
      accounting for 74.4% of our RMP-resistant strains. These results demonstrate that
      resistance genotyping at these codons would be a good marker for the rapid
      detection of RMP resistance.

PMID- 19861022
TI  - Wounded healers.

PMID- 19861023
TI  - The challenge of improving patient safety in primary care.

PMID- 19861024
TI  - Quality of life: what does it mean for general practice?

PMID- 19861025
TI  - Our debt to those who are dying: the UK medical establishment should reconsider
      its stance on assisted suicide.

PMID- 19861026
TI  - What happens when doctors are patients? Qualitative study of GPs.
AB  - BACKGROUND: Current evidence about the experiences of doctors who are unwell is
      limited to poor quality data. AIM: To investigate GPs' experiences of significant
      illness, and how this affects their own subsequent practice. DESIGN OF STUDY:
      Qualitative study using interpretative phenomenological analysis to conduct and
      analyse semi-structured interviews with GPs who have experienced significant
      illness. SETTING: Two primary care trusts in the West of England. METHOD: A total
      of 17 GPs were recruited to take part in semi-structured interviews which were
      conducted and analysed using interpretative phenomenological analysis Results:
      Four main categories emerged from the data. The category, 'Who cares when doctors
      are ill?' embodies the tension between perceptions of medicine as a 'caring
      profession' and as a 'system'. 'Being a doctor-patient' covers the role ambiguity
      experienced by doctors who experience significant illness. The category 'Treating
      doctor-patients' reveals the fragility of negotiating shared medical care.
      'Impact on practice' highlights ways in which personal illness can inform GPs'
      understanding of being a patient and their own consultation style. CONCLUSION:
      Challenging the culture of immunity to illness among GPs may require
      interventions at both individual and organisational levels. Training and
      development of doctors should include opportunities to consider personal health
      issues as well as how to cope with role ambiguity when being a patient and when
      treating doctor-patients. Guidelines about being and treating doctor-patients
      need to be developed, and GPs need easy access to an occupational health service.

PMID- 19861027
TI  - Primary care contact prior to suicide in individuals with mental illness.
AB  - BACKGROUND: Previous studies have reported differing rates of consultation with
      GPs prior to suicide. Patients with a psychiatric history have higher rates of
      consultation and consult closer to the time of their death. AIM: To investigate
      the frequency and nature of general practice consultations in the year before
      suicide for patients in current, or recent, contact with secondary mental health
      services. DESIGN OF STUDY: Retrospective case-note study and semi-structured
      interviews. SETTING: General practices in the northwest of England. METHOD:
      General practice data were obtained by a retrospective review of medical records
      (n = 247) and semi-structured interviews with GPs (n = 159). RESULTS: GP records
      were reviewed in 247 of the 286 cases (86%). Overall, 91% of individuals (n =
      224) consulted their GP on at least one occasion in the year before death. The
      median number of consultations was 7 (interquartile range = 3-10). Interviews
      were carried out with GPs with regard to 159 patients. GPs reported concerns
      about their patient's safety in 43 (27%) cases, but only 16% of them thought that
      the suicide could have been prevented. Agreement between GPs and mental health
      teams regarding risk of suicide was poor. Both sets of clinicians rated moderate
      to high levels of risk in only 3% of cases for whom information was available (n
      = 139) (overall kappa = 0.024). CONCLUSION: Consultation prior to suicide is
      common but suicide prevention in primary care is challenging. Possible strategies
      might include examining the potential benefits of risk assessment and
      collaborative working between primary and secondary care.

PMID- 19861028
TI  - Temporal change in health-related quality of life: a longitudinal study in
      general practice 1999-2004.
AB  - BACKGROUND: In order to assess and plan for changing healthcare needs, the lack
      of available information regarding temporal changes in the health-related quality
      of life of a population must be addressed. AIM: This paper aims to describe such
      changes over 5 years in a general population. DESIGN OF STUDY: Longitudinal
      postal questionnaire study. SETTING: UK general practice. METHOD: This was a
      longitudinal postal questionnaire study in two general practice populations,
      using the generic instrument EQ-5D to measure health-related quality of life.
      Individuals were included if they responded to three postal surveys in 1999,
      2001, and 2004 and there were three consecutive values of EQ-5D(index) available
      between 1999 and 2004. RESULTS: A total of 2498 subjects were included in the
      study. After adjustment for potential confounders (including ageing), health
      related quality of life declined significantly over the observation period. The
      change in EQ-5D(index) was from 0.79 to 0.74 and for EQ-5D(vas) 76.8 to 73.3 (P
      for both trends <0.001). CONCLUSION: Health-related quality of life deteriorated
      in these populations over 5 years. In an era of improvements in mortality, this
      has important implications for the use of health-related quality of life data in
      healthcare planning and resource allocation.

PMID- 19861029
TI  - GPs' views on the practice of physician-assisted suicide and their role in
      proposed UK legalisation: a qualitative study.
AB  - BACKGROUND: A bill to legalise assisted dying in the UK has been proposed in
      Parliament's House of Lords three times since 2003. The House of Lords Select
      Committee concluded in 2005 that 'the few attempts to understand the basis of
      doctors' views have shown equivocal data varying over time'. Fresh research was
      recommended to gain a fuller understanding of health sector views. AIM: To
      examine GPs' views of the practice of physician-assisted suicide as defined by
      the 2005/2006 House of Lords (Joffe) Bill and views of their role in the proposed
      legislation; and to explore the influences determining GPs' views on physician
      assisted suicide. DESIGN OF STUDY: Qualitative interview study. SETTING: Primary
      care in South London, England. METHOD: Semi-structured interviews with GPs were
      conducted by a lead interviewer and analysed in a search for themes, using the
      framework approach. RESULTS: Thirteen GPs were interviewed. GPs who had not
      personally witnessed terminal suffering that could justify assisted dying were
      against the legislation. Some GPs felt their personal religious views, which
      regarded assisted dying as morally wrong, could not be the basis of a
      generalisable medical ethic for others. GPs who had witnessed a person's
      suffering that, in their opinion, justified physician-assisted suicide were in
      favour of legislative change. Some GPs felt a specialist referral pathway to
      provide assisted dying would help to ensure proper standards were met.
      CONCLUSION: GPs' views on physician-assisted suicide ranged from support to
      opposition, depending principally on their interpretation of their experience of
      patients' suffering at the end of life. The goal to lessen suffering of the
      terminally ill, and apprehensions about patients being harmed, were common to
      both groups. Respect for autonomy and the right of self-determination versus the
      need to protect vulnerable people from the potential for harm from social
      coercion were the dominant themes.

PMID- 19861030
TI  - How useful are clinical guidelines for the management of obesity in general
      practice?
AB  - Obesity is a major public health issue and numerous clinical guidelines have been
      published to support management. One of the most comprehensive guidelines on
      obesity was published by the National Institute for Health and Clinical
      Excellence (NICE) in 2006 (NICE guideline 43) which aims to offer practical
      recommendations based on the available evidence and has a strong focus on primary
      care both in terms of prevention and clinical care. The current article
      summarises these guidelines in relation to primary care, reports on new evidence
      and developments since they were published, and critically appraises the
      usefulness of guidelines for management of obesity.

PMID- 19861031
TI  - Therapy for psychiatric therapy.

PMID- 19861032
TI  - Copying referral letters.

PMID- 19861034
TI  - Child and adolescent psychiatry liaison in Ireland.

PMID- 19861035
TI  - Genes, gender, sport, and justice.

PMID- 19861036
TI  - Diagnostic safety-netting.

PMID- 19861041
TI  - General practice at the margins: a student's experience of homelessness.

PMID- 19861044
TI  - A model-based assessment of oseltamivir prophylaxis strategies to prevent
      influenza in nursing homes.
AB  - Prophylaxis with neuraminidase inhibitors is important for controlling seasonal
      influenza outbreaks in long-term care settings. We used a stochastic individual
      based model that simulates influenza virus transmission in a long-term care
      nursing home department to study the protection offered to patients by different
      strategies of prophylaxis with oseltamivir and determined the effect of emerging
      resistance. Without resistance, postexposure and continuous prophylaxis reduced
      the patient infection attack rate from 0.19 to 0.13 (relative risk [RR] 0.67) and
      0.05 (RR 0.23), respectively. Postexposure prophylaxis prevented more infections
      per dose (118 and 323 daily doses needed to prevent 1 infection, respectively)
      and required fewer doses per season than continuous prophylaxis. If resistance to
      oseltamivir was increased, both prophylaxis strategies became less efficacious
      and efficient, but postexposure prophylaxis posed a lower selection pressure for
      resistant virus strains. Extension of prophylaxis to healthcare workers offered
      little additional protection to patients.

PMID- 19861045
TI  - Nontuberculous mycobacteria infections and anti-tumor necrosis factor-alpha
      therapy.
AB  - Patients receiving anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy are
      at increased risk for tuberculosis and other granulomatous diseases, but little
      is known about illness caused by nontuberculous mycobacteria (NTM) in this
      setting. We reviewed the US Food and Drug Administration MedWatch database for
      reports of NTM disease in patients receiving anti-TNF-alpha therapy. Of 239
      reports collected, 105 (44%) met NTM disease criteria. Median age was 62 years;
      the majority of patients (66, 65%) were female, and most (73, 70%) had rheumatoid
      arthritis. NTM infections were associated with infliximab (n = 73), etanercept (n
      = 25), and adalimumab (n = 7); most patients were taking prednisone (n = 68, 65%)
      or methotrexate (n = 58, 55%) concurrently. Mycobacteria avium (n = 52, 50%) was
      most commonly implicated, and 9 patients (9%) had died at the time their
      infections were reported. A high rate of extrapulmonary manifestations (n = 46,
      44%) was also reported.

PMID- 19861046
TI  - Nontuberculous mycobacteria-associated lung disease in hospitalized persons,
      United States, 1998-2005.
AB  - The prevalence and trends of pulmonary nontuberculous mycobacteria (NTM)
      associated hospitalizations in the United States were estimated using national
      hospital discharge data. Records were extracted for all persons with a pulmonary
      NTM International Classification of Diseases code (031.0) hospitalized in the 11
      states with continuous data available from 1998 through 2005. Prevalence was
      calculated using US census data. Pulmonary NTM hospitalizations (031.0) increased
      significantly with age among both sexes: relative prevalence for persons 70-79
      years of age compared with those 40-49 years of age was 15/100,000 for women (9.4
      vs. 0.6) and 9/100,000 for men (7.6 vs. 0.83). Annual prevalence increased
      significantly among men and women in Florida (3.2%/year and 6.5%/year,
      respectively) and among women in New York (4.6%/year) with no significant changes
      in California. The prevalence of pulmonary NTM-associated hospitalizations is
      increasing in selected geographic areas of the United States.

PMID- 19861047
TI  - Mycobacterium tuberculosis genotype and case notification rates, rural Vietnam,
      2003-2006.
AB  - Tuberculosis case notification rates (CNRs) for young adults in Vietnam are
      increasing. To determine whether this finding could reflect emergence of
      Mycobacterium tuberculosis Beijing genotype, we studied all new sputum smear
      positive pulmonary tuberculosis patients registered for treatment in 3 rural
      districts in Vietnam during 2003-2006. Beijing strain infections were more
      frequent in younger patients (15-24 years of age, 53%) than in older patients
      (31%; p<0.001). The increase in CNRs for youngest patients was larger for disease
      caused by the Beijing genotype than by other genotypes, but the difference was
      not significant. For patients 15-24 years of age, 85% of fluctuations in CNRs
      between years was caused by fluctuations in Beijing genotype infections compared
      with 53% and 23% in the groups 25-64 and >or=65 years of age, respectively
      (p<0.001). These findings suggest that young adults may be responsible for
      introducing Beijing strains into rural Vietnam.

PMID- 19861048
TI  - Lack of airborne transmission during outbreak of pandemic (H1N1) 2009 among tour
      group members, China, June 2009.
AB  - During June 2-8, 2009, an outbreak of influenza A pandemic (H1N1) 2009 occurred
      among 31 members of a tour group in China. To identify the mode of transmission
      and risk factors, we conducted a retrospective cohort investigation. The index
      case-patient was a female tourist from the United States. Secondary cases
      developed in 9 (30%) tour group members who had talked with the index case
      patient and in 1 airline passenger (not a tour group member) who had sat within 2
      rows of her. None of the 14 tour group members who had not talked with the index
      case-patient became ill. This outbreak was apparently caused by droplet
      transmission during coughing or talking. That airborne transmission was not a
      factor is supported by lack of secondary cases among fellow bus and air
      travelers. Our findings highlight the need to prevent transmission by droplets
      and fomites during a pandemic.

PMID- 19861049
TI  - Community-associated methicillin-resistant Staphylococcus aureus, Iowa, USA.
AB  - We performed antimicrobial drug susceptibility testing and molecular typing on
      invasive methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 1,666)
      submitted to the University of Iowa Hygienic Laboratory during 1999-2006 as part
      of a statewide surveillance system. All USA300 and USA400 isolates were resistant
      to <or=3 non-beta-lactam antimicrobial drug classes. The proportion of MRSA
      isolates from invasive infections that were either USA300 or USA400 increased
      significantly from 1999-2005 through 2006 (p<0.0001). During 2006, the incidence
      of invasive community-associated (CA)-MRSA infections was highest in the summer
      (p = 0.0004). Age <69 years was associated with an increased risk for invasive CA
      MRSA infection (odds ratio [OR] 5.1, 95% confidence interval [CI] 2.06-12.64),
      and hospital exposure was associated with decreased risk (OR 0.07, 95% CI 0.01
      0.51).

PMID- 19861050
TI  - Healthcare worker occupation and immune response to Pneumocystis jirovecii.
AB  - The reservoir and mode of transmission of Pneumocystis jirovecii remain
      uncertain. We conducted a cross-sectional study of 126 San Francisco General
      Hospital staff in clinical (n = 103) and nonclinical (n = 23) occupations to
      assess whether occupational exposure was associated with immune responses to P.
      jirovecii. We examined antibody levels by ELISA for 3 overlapping fragments that
      span the P. jirovecii major surface glycoprotein (Msg): MsgA, MsgB, and MsgC1.
      Clinical occupation participants had higher geometric mean antibody levels to
      MsgC1 than did nonclinical occupation participants (21.1 vs. 8.2, p = 0.004);
      clinical occupation was an independent predictor of higher MsgC1 antibody levels
      (parameter estimate = 0.89, 95% confidence interval 0.29-1.48, p = 0.003). In
      contrast, occupation was not significantly associated with antibody responses to
      either MsgA or MsgB. Healthcare workers may have occupational exposure to P.
      jirovecii. Humans may be a reservoir for P. jirovecii and may transmit it from
      person to person.

PMID- 19861053
TI  - Review of an influenza surveillance system, Beijing, People's Republic of China.
AB  - In 2007, a surveillance system for influenza-like illness (ILI) and virologic
      data was established in Beijing, China. The system tracked ILI and laboratory
      confirmed influenza in 153 general hospitals from September 1, 2007, through
      April 30, 2008. To analyze the ILI surveillance data (weekly ILI rates and
      counts) and the effectiveness of the system, we used the US Centers for Disease
      Control and Prevention Early Aberration Reporting System. The data indicated that
      the highest rate of influenza isolation and the highest ILI count occurred in the
      first week of 2008. The system enabled us to detect the onset and peak of an
      epidemic.

PMID- 19861052
TI  - Nosocomial outbreak of novel arenavirus infection, southern Africa.
AB  - A nosocomial outbreak of disease involving 5 patients, 4 of whom died, occurred
      in South Africa during September-October 2008. The first patient had been
      transferred from Zambia to South Africa for medical management. Three cases
      involved secondary spread of infection from the first patient, and 1 was a
      tertiary infection. A novel arenavirus was identified. The source of the first
      patient's infection remains undetermined.

PMID- 19861055
TI  - Excess deaths and immunoprotection during 1918-1920 influenza pandemic, Taiwan.
AB  - To determine the difference in age-specific immunoprotection during waves of
      influenza epidemics, we analyzed excess monthly death data for the 1918-1920
      influenza pandemic in Taiwan. For persons 10-19 years of age, percentage of
      excess deaths was lowest in 1918 and significantly higher in 1920, perhaps
      indicating lack of immunoprotection from the first wave.

PMID- 19861054
TI  - Discriminatory ability of hypervariable variable number tandem repeat loci in
      population-based analysis of Mycobacterium tuberculosis strains, London, UK.
AB  - To address conflicting results about the stability of variable number tandem
      repeat (VNTR) loci and their value in prospective molecular epidemiology of
      Mycobacterium tuberculosis, we conducted a large prospective population-based
      analysis of all M. tuberculosis strains in a metropolitan setting. Optimal and
      reproducible conditions for reliable PCR and fragment analysis, comprising
      enzymes, denaturing conditions, and capillary temperature, were identified for a
      panel of hypervariable loci, including 3232, 2163a, 1982, and 4052. A total of
      2,261 individual M. tuberculosis isolates and 265 sets of serial isolates were
      analyzed by using a standardized 15-loci VNTR panel, then an optimized
      hypervariable loci panel. The discriminative ability of loci varied
      substantially; locus VNTR 3232 varied the most, with 19 allelic variants and
      Hunter-Gaston index value of 0.909. Hypervariable loci should be included in
      standardized panels because they can provide consistent comparable results at
      multiple settings, provided the proposed conditions are adhered to.

PMID- 19861056
TI  - Rabies in foxes, Aegean region, Turkey.
AB  - At the end of the 1990s in the Aegean region of Turkey, rabies rapidly spread
      among foxes. This spread likely resulted from spillover infection from dogs and
      led to increased rabies cases among cattle. To control this outbreak, oral rabies
      vaccination of foxes has been used.

PMID- 19861057
TI  - Fine-scale identification of the most likely source of a human plague infection.
AB  - We describe an analytic approach to provide fine-scale discrimination among
      multiple infection source hypotheses. This approach uses mutation-rate data for
      rapidly evolving multiple locus variable-number tandem repeat loci in
      probabilistic models to identify the most likely source. We illustrate the
      utility of this approach using data from a North American human plague
      investigation.

PMID- 19861058
TI  - Borrelia hispanica relapsing fever, Morocco.
AB  - We found that 20.5% of patients with an unexplained fever in northwestern Morocco
      had tick-borne relapsing fever. Molecular detection specific for the 16S rRNA
      gene identified Borrelia hispanica. The noncoding intergenic spacer sequence
      domain showed high sensitivity and good resolution for this species.

PMID- 19861059
TI  - Diversity and origin of dengue virus serotypes 1, 2, and 3, Bhutan.
AB  - To determine the serotype and genotype of dengue virus (DENV) in Bhutan, we
      conducted phylogenetic analyses of complete envelope gene sequences. DENV-2
      (Cosmopolitan genotype) predominated in 2004, and DENV-3 (genotype III)
      predominated in 2005-2006; these viruses were imported from India. Primary dengue
      infections outnumbered secondary infections, suggesting recent emergence.

PMID- 19861060
TI  - Ducks as sentinels for avian influenza in wild birds.
AB  - To determine the effectiveness of ducks as sentinels for avian influenza virus
      (AIV) infection, we placed mallards in contact with wild birds at resting sites
      in Germany, Austria, and Switzerland. Infections of sentinel birds with different
      AIV subtypes confirmed the value of such surveillance for AIV monitoring.

PMID- 19861061
TI  - Immunologic response of unvaccinated workers exposed to anthrax, Belgium.
AB  - To determine immunologic reactivity to Bacillus anthrax antigens, we conducted
      serologic testing of workers in a factory that performed scouring of wool and
      goat hair. Of 66 workers, approximately 10% had circulating antibodies or T
      lymphocytes that reacted with anthrax protective antigen. Individual immunity
      varied from undetectable to high.

PMID- 19861062
TI  - Molecular epidemiology of clade 1 influenza A viruses (H5N1), southern Indochina
      peninsula, 2004-2007.
AB  - To determine the origin of influenza A virus (H5N1) epizootics in Cambodia, we
      used maximum-likelihood and Bayesian methods to analyze the genetic sequences of
      subtype H5N1 strains from Cambodia and neighboring areas. Poultry movements,
      rather than repeated reintroduction of subtype H5N1 viruses by wild birds, appear
      to explain virus circulation and perpetuation.

PMID- 19861063
TI  - Melioidosis in a tropical city state, Singapore.
AB  - The incidence of melioidosis in Singapore decreased during 1998-2007, with the
      exception of the first quarter of 2004. After heavy rainfalls, an increase in
      pneumonic cases with a high case-fatality rate was detected. We show that
      melioidosis has the potential to reemerge following adverse climate events.

PMID- 19861064
TI  - Escherichia coli as reservoir for macrolide resistance genes.
AB  - The plasmid-borne mph(A) gene that confers resistance to azithromycin and has
      recently emerged in Shigella sonnei is present in multidrug- and non-multidrug
      resistant Escherichia coli isolates from 4 continents. Further spread of mph(A)
      to Shigella and Salmonella spp. may be expected.

PMID- 19861065
TI  - West Nile virus antibodies in wild birds, Morocco, 2008.
AB  - To determine circulation of West Nile virus (WNV) during nonepidemic times, we
      serosurveyed wild birds of Morocco in 2008. We found antibodies against WNV in 12
      (3.5%) birds, against Usutu virus in 1 (0.3%), and against both in 2 (0.6%). High
      WNV prevalence among juvenile birds suggests local virus circulation among
      resident birds.

PMID- 19861066
TI  - Novel rickettsia in ticks, Tasmania, Australia.
AB  - A novel rickettsia was detected in Ixodes tasmani ticks collected from Tasmanian
      devils. A total of 55% were positive for the citrate synthase gene by
      quantitative PCR. According to current criteria for rickettsia speciation, this
      new rickettsia qualifies as Candidatus Rickettsia tasmanensis, named after the
      location of its detection.

PMID- 19861067
TI  - Orangutans not infected with Plasmodium vivax or P. cynomolgi, Indonesia.
AB  - After orangutans in Indonesia were reported as infected with Plasmodium cynomolgi
      and P. vivax, we conducted phylogenetic analyses of small subunit ribosomal RNA
      gene sequences of Plasmodium spp. We found that these orangutans are not hosts of
      P. cynomolgi and P. vivax. Analysis of >or=1 genes is needed to identify
      Plasmodium spp. infecting orangutans.

PMID- 19861068
TI  - Acute Q fever and scrub typhus, southern Taiwan.
AB  - Acute Q fever and scrub typhus are zoonoses endemic to southern Taiwan. Among the
      137 patients with acute Q fever (89, 65.0%) or scrub typhus (43, 31.4%), we
      identified 5 patients (3.6%) who were co-infected with Coxiella burnetii and
      Orientia tsutsugamushi.

PMID- 19861069
TI  - Poor clinical sensitivity of rapid antigen test for influenza A pandemic (H1N1)
      2009 virus.
AB  - Influenza A pandemic (H1N1) 2009 virus RNA was detected by reverse transcription
      PCR in 144 clinical samples from Bonn, Germany. A common rapid antigen-based test
      detected the virus in only 11.1% of these samples. The paramount feature of rapid
      test-positive samples was high virus concentration. Antigen-based rapid tests
      appear unsuitable for virologic diagnostics in the current pandemic.

PMID- 19861070
TI  - Human rickettsialpox, southeastern Mexico.
AB  - The detection of Rickettsia akari in 2 human patients increased the diversity of
      rickettsioses affecting the public health in the southeast of Mexico.
      Rickettsialpox should be considered in the differential diagnosis with other
      febrile illnesses for the correct diagnosis and accurate treatment of this
      potential threat to human health.

PMID- 19861071
TI  - West Nile virus infection in plasma of blood and plasma donors, United States.
AB  - This study investigated the association of ongoing West Nile virus (WNV)
      infections with neutralizing antibody titers in US plasma-derived intravenous
      immune globulin released during 2003-2008. Titers correlated closely with the
      prevalence of past WNV infection in blood donors, with 2008 lots indicating a
      prevalence of 1%.

PMID- 19861072
TI  - Tick-borne encephalitis from eating goat cheese in a mountain region of Austria.
AB  - We report transmission of tick-borne encephalitis virus (TBEV) in July 2008
      through nonpasteurized goat milk to 6 humans and 4 domestic pigs in an alpine
      pasture 1,500 m above sea level. This outbreak indicates the emergence of ticks
      and TBEV at increasing altitudes in central Europe and the efficiency of oral
      transmission of TBEV.

PMID- 19861073
TI  - Surveillance system for infectious diseases of pets, Santiago, Chile.
AB  - Pet diseases may pose risks to human health but are rarely included in
      surveillance systems. A pilot surveillance system of pet infectious diseases in
      Santiago, Chile, found that 4 canine and 3 feline diseases accounted for 90.1%
      and 98.4% of notifications, respectively. Data also suggested association between
      poverty and pet diseases.

PMID- 19861074
TI  - Independent lineage of lymphocytic choriomeningitis virus in wood mice (Apodemus
      sylvaticus), Spain.
AB  - To clarify the presence of lymphocytic choriomeningitis virus (LCMV) in Spain, we
      examined blood and tissue specimens from 866 small mammals. LCMV RNA was detected
      in 3 of 694 wood mice (Apodemus sylvaticus). Phylogenetic analyses suggest that
      the strains constitute a new evolutionary lineage. LCMV antibodies were detected
      in 4 of 10 rodent species tested.

PMID- 19861075
TI  - Influenza (H1N1) 2009 outbreak and school closure, Osaka Prefecture, Japan.

PMID- 19861076
TI  - Maximizing the value of drug stockpiles for pandemic influenza.

PMID- 19861077
TI  - Intrafamilial transmission of methicillin-resistant Staphylococcus aureus.

PMID- 19861078
TI  - Rhombencephalitis and coxsackievirus A16.

PMID- 19861079
TI  - Japanese encephalitis in hill and mountain districts, Nepal.

PMID- 19861080
TI  - Ceftazidime-resistant Salmonella enterica, Morocco.

PMID- 19861081
TI  - Lessons from a special service for public health, Brazil.

PMID- 19861082
TI  - Group B streptococcus meningitis in a child with cochlear implant.

PMID- 19861083
TI  - Severe necrotizing pneumonia in children, Houston, Texas, USA.

PMID- 19861084
TI  - Human bocavirus 2 in children, South Korea.

PMID- 19861085
TI  - Nontuberculous mycobacteria infection and tumor necrosis factor-alpha
      antagonists.

PMID- 19861086
TI  - Transmission of varicella vaccine virus, Japan.

PMID- 19861087
TI  - Aichi virus strains in children with gastroenteritis, China.

PMID- 19861088
TI  - Appropriate screening for leishmaniasis before immunosuppressive treatments.

PMID- 19861090
TI  - [Scaling methods applied to set priorities in training programs in
      organizations].
AB  - Criteria to assess the needs in order to plan training programs are not usually
      defined explicitly in organizational contexts. We propose scaling methods as a
      feasible and useful procedure to set priorities of training programs; also, we
      propose the most suitable method for this intervention context. 404 employees
      from a public organization completed an ad hoc questionnaire to assess training
      needs in different areas from 2004 to 2006; concretely, 117, 75 and 286 stimuli
      were scaled, respectively. Then, four scaling methods were compared: Dunn
      Rankin's method and three methods derived from Thurstone's Law of Categorical
      Judgment--ranking, successive intervals and equal-appearing intervals. The
      feasibility and utility of these scaling methods to solve the problems described
      is shown. Taking into account the most accurate compared methods, we propose
      ranking as the most parsimonious method (with regard to procedure simplicity).
      Future research developments are described.

PMID- 19861091
TI  - Leader charisma and affective team climate: the moderating role of the leader's
      influence and interaction.
AB  - In this study, we evaluate the role of leader charisma in fostering positive
      affective team climate and preventing negative affective climate. The analysis of
      a longitudinal database of 137 bank branches by means of hierarchical moderated
      regression shows that leader charisma has a stronger effect on team optimism than
      on team tension. In addition, the leader's influence and the frequency of leader
      team interaction moderate the relationship between charisma and affective
      climate. However, whereas the leader's influence enhances the relationship
      between leader charisma and positive affective climate, the frequency of
      interaction has counterproductive effects.

PMID- 19861092
TI  - Naming faces: a multidisciplinary and integrated review.
AB  - Naming faces is a common area of study from a wide range of perspectives in
      social sciences, including cognitive psychology and several branches of cognitive
      neuroscience. This paper provides a comprehensive review of the cognitive models
      that have been proposed to explain the diverse aspects of face naming, taking
      into account face processing and language production models. In addition, a
      review of the neuroscientific data from event-related potential studies (when)
      and functional neuroimaging studies (where) is presented. Thus, an integrated
      view of the cognitive models and the data relating the different processes
      involved in naming faces to the brain activity is provided.

PMID- 19861093
TI  - The effect of amitriptyline on inhibitory avoidance in mice is dose-dependent.
AB  - The purpose of the present work was to study the dose-effect relationship of the
      antidepressant amitriptyline on inhibitory avoidance in male and female mice.
      Subjects received physiological saline or 2.5, 5, 10 or 20 mg/kg of amitriptyline
      hydrochloride 30 min before the training phase, and were subjected to the test
      phase 24 h later. Results showed a clear impairing effect of amitriptyline on
      inhibitory avoidance in both male and female mice, and that the effect is dose
      dependent.

PMID- 19861094
TI  - Heart-rate variability and precompetitive anxiety in swimmers.
AB  - The aim of this study was to test the utility of heart-rate variability (HRV)
      analyses as a noninvasive means of quantifying cardiac autonomic regulation
      during precompetitive anxiety situations in swimmers. Psychophysiological state
      evaluation of 10 volunteer <<master>> swimmers (6 women and 4 men) was obtained
      by comparing baseline training condition (TC) with competition condition (CC).
      Self-evaluation of precompetitive somatic anxiety measured by CSAI-2 showed
      significant increase from the TC to CC. Analysis showed that during higher
      precompetitive anxiety level, a significant reduction in the timing (RMSSD),
      frequency (HFms2 and HFnu) and Poincare plot (SD1) of heart-rate variability was
      observed, and a significant increase in the low frequency to high frequency ratio
      (LF/HF %). The results indicate a shift towards sympathetic predominance as a
      result of parasympathetic withdrawal. Our results provide an HRV analysis in a
      valid, useful and non-invasive way to evaluate the change of sympathovagal
      balance in presence of precompetitive stress.

PMID- 19861095
TI  - [Social reputation and relational violence in adolescents: the role of
      loneliness, self-esteem and life satisfaction].
AB  - The aim of the current study was to analyse the relationship among adolescents'
      social reputation--perceived and ideal--, relational violence at the school
      context and their specific psychosocial adjustment variables such as loneliness,
      self-esteem and life satisfaction. The sample comprised 1319 adolescents aged 11
      to 16 years old. Results suggested that adolescents who wish for and seek a non
      conforming social reputation (ideal) report more loneliness, have lower self
      esteem and feel more dissatisfied with their lives, factors all linked to higher
      participation in behaviours involving relational violence. Conversely,
      adolescents who already have a non-conforming social reputation (perceived)
      report less feelings of loneliness and higher levels of self-esteem and life
      satisfaction, thus having less involvement in acts of relational violence.
      Associations among the variables included in the structural model were also
      analysed as a function of sex.

PMID- 19861096
TI  - [Educational system and equal opportunities for young people in care: recent
      studies in the UK].
AB  - Publications on research about formal educational itineraries of people who were
      cared for by the social protection public systems when they were children are
      scarce, and restricted to a few countries. In recent years, statistics from some
      European countries have been published, showing that the young people who were
      cared for are overrepresented in practically all the clusters of people that
      accumulate indicators of social disadvantage, and it has therefore been argued
      that they can be considered one of the groups of population with the highest risk
      for social exclusion. In the present review, the emergence of new data and
      research results in some European countries--particularly in the United Kingdom,
      where the fact that less than 5% of this population reaches university studies
      has been underlined--is tentatively contextualised. Although the extent to which
      current available data can be extrapolated to other contexts and countries is yet
      unclear, such results raise important challenges for social intervention and
      social policies, as well as for psychosocial research, in all countries of the
      European space.

PMID- 19861097
TI  - [Personal self-regulation and perceived maladjusted school behaviors].
AB  - The purpose of this study is to confirm the extent to which subjects' ability to
      self-regulate, during mid-adolescence, influences their perception of
      maladjustment problems. The sample comprised 888 adolescents between 12 and 17
      years of age. The study followed an inferential methodology, using two
      instruments, a Spanish version of the Personal Self-regulation Questionnaire
      (2003, 2007) and the Cuestionario de Problemas de Desadaptacion Escolar
      [Questionnaire for the Assessment of School Maladjustment Problems] (2007) to
      measure the variables of interest. Results from the inferential analyses (ANOVAS)
      suggest that the degree of personal self-regulation is interdependent with
      respect to perceived maladjustment and relational problems at school. Results and
      implications for future research are discussed.

PMID- 19861098
TI  - [Intellectual styles and academic achievement: a developmental perspective].
AB  - The aim of the present study is to provide additional information to highlight
      some aspects concerning the relationship between thinking styles and academic
      achievement. In order to understand the extent to which thinking styles predict
      academic achievement, 1466 students, between 12 and 16 years old, from first to
      fourth grades of Compulsory Secondary Education (Spanish ESO) took part in the
      research. A parsimonious model of covariances was assumed in each of the four
      samples corresponding to the four different grades of Secondary School as well as
      in the total sample. Data show that thinking styles significantly explain part of
      the variance of academic achievement, although only about 10%.

PMID- 19861099
TI  - [Torrance Tests of Creative Thinking (TTCT): elements for construct validity in
      Portuguese adolescents].
AB  - The aim of this work is to study the unidimensional and multidimensional nature
      of creativity when assessed through divergent thinking tasks, as proposed in
      Torrance's battery (Torrance Creative Thinking Test, TTCT). This battery is made
      up of various tasks with verbal and figurative content, aimed at estimating the
      level of creativity according to the dimensions or cognitive functions of
      fluency, flexibility, originality and elaboration of the individuals' ideas. This
      work used a sample of 595 Portuguese students from 5th and 6th grade. The results
      of confirmatory factor analysis reveals that the unidimensional model (a general
      factor of creativity) and the model of factors as a function of the cognitive
      dimensions of creativity, based on task content, do not fit well. The model with
      the best fit has a hierarchical factor structure, in which the first level
      comprises the factors for each of the subtests applied and the second level
      includes verbal or figurative content. The difficulty to verify the structural
      validity of the TTCT is noted, and the need for further studies to achieve, in
      practice, better individual creativity scores.

PMID- 19861100
TI  - [Analysis of the cognitive structure of scientific competence in PISA-2006 by
      means of the Least Squares Distance Method (LSDM): the Spanish case].
AB  - The cognitive diagnosis approach links Psychometrics and Cognitive Psychology in
      order to obtain detailed measurements of the processes and cognitive attributes
      required to solve test items. In this context, the Least Squares Distance Method
      (LSDM) employs item parameters, calibrated with any Item Response Theory (IRT)
      model, to analyze the attributes and provide evidence about the validity of the
      cognitive structure. The Organization for Economic Cooperation and Development
      (OECD) determines three cognitive attributes underlying students' performance in
      the PISA-2006 science items: a) identifying scientific issues, b) explaining
      phenomena scientifically and c) using scientific evidence. The aim of the present
      work is to analyze these processes and collect evidence of the cognitive
      structure proposed by the OECD, using the LSDM. A second aim is to compare the
      probabilities of mastering the attributes of the Spanish Communities. The results
      show that the proposed structure is appropriate to explain students' proficiency
      in the science items, and also, significant differences between three Spanish
      Communities were found.

PMID- 19861101
TI  - [Smoking among psychology students over a ten-year period (1996-2006)].
AB  - The purpose of this study was to analyze the evolution of smoking among
      Psychology students at the University of Santiago de Compostela (Spain) over a
      ten-year period (1986-2006). We also assessed the extent of knowledge of the
      Spanish health legislation on tobacco (Ley 28/2005) and its effect on smoking. We
      administered a questionnaire to representative samples of students from the 1st
      year of their Psychology course to the 5th year, on four occasions. In the
      academic year 1996-1997 (N = 835), 34% of the sample claimed to be daily smokers;
      in 1999-2000 (N = 842), the figure was 35.2%; in 2003-2004 (N = 835) it was
      31.9%; and in 2006-2007 (N = 688), it was 22.8%. Moreover, in the last
      assessment, 97.1% of the sample reported being aware of the legislation (Ley
      28/2005) and 41.9% of the smokers claimed that it had some degree of influence on
      their smoking. It can be stated that, although overall current prevalence of
      smoking is similar to that of 10 years ago, a significant change is observed in
      the profile of smokers. This change is expressed in lower levels of nicotine
      dependence and a decrease in the percentage of daily smokers, together with an
      increase in occasional smokers.

PMID- 19861102
TI  - [The Nicotine Dependence Syndrome Scale (NDSS) in a sample of smokers who demand
      smoking cessation treatment].
AB  - The Nicotine Dependence Syndrome Scale (NDSS) was applied to a sample of 241
      smokers who demanded treatment to stop smoking. The results indicate good
      reliability (Cronbach's alpha = 0.80) of the general factor that evaluates
      nicotine dependence (NDSS-T), and the five original factors obtained by factor
      analysis are confirmed (drive, continuity, tolerance, priority and stereotypy).
      The NDSS-T correlates significantly with the Fagerstrom Test for Nicotine
      Dependence, with DSM-IV diagnostic criteria assessed with the SCID, the number of
      cigarettes smoked and carbon monoxide in expired air. The ROC curves show that
      the NDSS-T has a score of 0.86 under the curve, which indicates a good prediction
      of nicotine dependence. All the results obtained in this study indicate the
      utility of this scale to assess nicotine dependence in smokers.

PMID- 19861103
TI  - [Assessment of functional and dysfunctional impulsivity in substance-addicted
      patients by means of Dickman's Inventory].
AB  - Impulsivity is a dispositional trait consistently linked to addiction.
      Nevertheless, Dickman proposed two different types of impulsivity, a functional
      variant and another, dysfunctional one. Almost all studies in addiction have
      exclusively explored the dysfunctional facet of impulsivity. The main purpose of
      this study was to check the applicability of the Dickman Impulsivity Inventory to
      explore both types of impulsivity in addicted individuals. We applied a Spanish
      version of the inventory and studied its psychometric properties. We found
      adequate internal consistency, construct validity and convergence of measures
      with related instruments, both in non-clinical (N = 398) and in treated substance
      addicted (diacetylmorphine, cocaine, alcohol and cannabis; N = 140) samples.
      Addicted individuals did not differ from the non-clinical population in their
      functional impulsivity, but we found a great effect size (eta2p = 0.35) in the
      differences when exploring the dysfunctional type, with higher scores in addicts.
      Dysfunctional impulsivity was related to dysexecutive symptoms (r2 = 0.39), and
      personality traits such as Novelty Seeking (r2 = 0.57), but not with the
      Exploratory Excitability subdimension (r2 = 0.01), this latter being more closely
      related to functional impulsivity (r2 = 0.16). Data support the usefulness of
      this inventory to estimate types of impulsivity related to the prevention and
      treatment of addictive behaviors.

PMID- 19861104
TI  - [Comorbidity characteristics in the different subtypes of attention deficit
      hyperactivity disorder].
AB  - Cormobidity characteristics in attention deficit-hyperactivity disorder (ADHD)
      have an important impact on the subjects' behaviour, learning and cognitive
      development. It has been proposed that certain comorbidity characteristics depend
      on the ADHD subtype (inattentive vs. hyperactive-impulsive). In this article, a
      neuropsychological analysis is presented of the comorbidity characteristics in 61
      children with an ADHD diagnosis, divided into inattentive versus hyperactive
      impulsive. The empirical results support the proposed conceptual division.
      Moreover, differences between cases with hyperactivity-without-impulsivity and
      cases with impulsivity with or without hyperactivity were analysed, and the
      findings revealed some significant differences and a differentiation tendency.
      The discussion is developed based on Barkley's and Diamond's models. It is
      concluded that a neuropsychological division reveals certain comorbidity
      characteristics in ADHD, resulting in a more precise description and the
      possibility of more specific treatment for each subgroup.

PMID- 19861105
TI  - [Assessment of stress in childhood: Children's Daily Stress Inventory (Inventario
      Infantil de Estresores Cotidiano, IIEC)].
AB  - The present study introduces the Children's Daily Stress Inventory (Inventario
      Infantil de Estresores Cotidianos, IIEC) as a measure that assesses daily stress
      in primary school children. The inventory was applied to a sample of 1094 primary
      school students. The final version includes 25 dichotomic items covering the
      areas of health, school/peers, and family. The score is obtained by adding the
      total of positive answers. Analyses of items, reliability and several external
      pieces of evidence of validity based on relations with other variables are
      presented. The results show adequate psychometric properties for the assessment
      of daily stress in children.

PMID- 19861106
TI  - [The effect of "hospital clowns" on distress and maladaptive behaviours of
      children who are undergoing minor surgery].
AB  - The presence of clowns in health care settings is a program used in many
      countries to reduce distress in children who are undergoing surgery. The aim of
      the present study is to determine the effect of the presence of clowns on
      children's distress and maladaptive behaviours while in hospital for minor
      surgery. The sample consisted of 61 pediatric patients (aged 3-12 years)
      undergoing general anesthesia for minor surgery. Participants were assigned to
      two groups: experimental and control group. The child's distress was assessed
      using FAS (Facial Affective Scale). Postoperative maladaptive behaviors were
      evaluated one week after surgery, using the PHBQ (Post-Hospital Behavior
      Questionnaire). Our results suggest that clowns are not able to reduce the
      child's level of distress. However, postoperative maladaptive behaviours in the
      experimental group decreased, but the decrease was not statistically significant.
      Further research is needed to determine the effects of clowns in hospitals,
      taking into account age, sex, parents' presence, and diverse hospital settings.

PMID- 19861107
TI  - [Assessment of personality disorders with the Millon Clinical Multiaxial
      Inventory (MCMI-II) in a forensic sample].
AB  - In this paper, the presence of personality disorders in a forensic sample is
      analysed using the Millon Clinical Multiaxial Inventory (MCMI-II). The sample was
      made up of 86 individuals from both civil and criminal settings: plaintiffs in
      family cases and complainants and defendants in various crimes, especially in
      partner abuse. The results reveal a great number of records of Compulsive
      Personality Disorder, reaching 70%, regardless of whether they were from the
      civil or the criminal setting or whether they were a plaintiff or a defendant. It
      is concluded that this inventory seems to lack statistical validity for this
      purpose. Moreover, this test may only describe the typical characteristics of
      forensic evaluation rather than the personality of the individuals assessed, and
      it is oversensitive to context; hence, the conclusions derived from the use of
      the MCMI-II in the forensic field may accept as valid a great deal of distorted
      or unspecific profiles.

PMID- 19861108
TI  - [Outcome assessment in the Spanish young offenders' law. Recidivism and
      associated factors].
AB  - The present study aims to assess the impact of the Spanish young offenders law
      (LO/2000). Recidivism and its associated risk factors were used as indicators of
      impact. Data were collected from young offenders' reports opened after 2001 and
      closed before 2005. The final sample consisted of 382 young offenders (327 males
      and 55 females). Results indicated that 70% had not re-offended in an average
      period of 1.6 years. Most of the youngsters with fewer risk factors, usually
      start their criminal careers with less serious offences and the interventions
      seemed to be fairly effective. In the cases of young offenders with a higher
      number of risk factors, the interventions (custodial and non-custodial) were less
      effective, as recidivism rates were higher. Interventions must focus on family
      and community contexts in order to achieve adequate social integration of young
      delinquents.

PMID- 19861109
TI  - [Beliefs about the adversary, political violence and peace processes].
AB  - The aim of this study is to test in a real political context whether or not a
      change in the beliefs which were fueling the political violence in question is
      required during the advent of a peace process. Two hypothesis are considered: a)
      in the case of these beliefs not being modified, there will be difficulties to
      reach an atmosphere of trust between both parts and the process will fail, and b)
      if this happens, the groups will develop more extreme beliefs against the
      opponent. The results obtained through a textual analysis support both
      hypotheses. During the failure of the peace process, neither the strategy of the
      delegitimization of the opponent nor the identities in conflict were modified.
      Consequently, when the process failed, responsibility for this failure was
      attributed to the opponent, and, at the same time, delegitimization against the
      opponent intensified.

PMID- 19861110
TI  - [Foucault's relevance for psychology].
AB  - In this article, we will attempt to address one of the most outstanding and
      influential thinkers of the past century: Michel Foucault, Philosopher,
      Psychologist, and above all (university) Professor. Michel Foucault is certainly
      versatile: Historian (of madness, clinical practice, imprisonment and sexuality),
      Archaeologist (of knowledge), Analyst (of discourse and power relations),
      Psychologist (genealogy of subjectivity) and Philosopher (of power and the
      subject). With this article, we eventually expect to offer some clues to be able
      to use the work of Michel Foucault for the problematization of Psychology.

PMID- 19861111
TI  - [Spanish adaptation and factor structure of the Denison Organizational Culture
      Survey].
AB  - This article presents a Spanish adaptation of the Denison Organizational Culture
      Survey, a questionnaire designed to evaluate organizational culture. This survey
      consists of 60 items, grouped in 12 subscales, which identify 4 cultural
      dimensions. These dimensions have been widely studied and their influence in
      organizational effectiveness has been accepted. This adaptation was applied to
      488 participants, and analysed with confirmatory factor analysis. Results show
      adequate psychometric properties, so it can be concluded that the Spanish
      adaptation almost completely replicates the structure of the original version in
      English.

PMID- 19861112
TI  - [Goodness of fit in polytomous items: Type I error rates and empirical power for
      three fit-indexes].
AB  - Applications of Item Response Theory require assessing the agreement between
      observations and model predictions at the item level. This paper compares
      approaches applied to polytomous scored items in a simulation study. Three fit
      indexes are calculated: traditional chi-square index obtained by grouping
      examinees according to their estimated trait, an alternative that uses posterior
      distribution of trait and the third method, in which examinees are grouped
      according their observed total scores. Various conditions are simulated by
      manipulating test length (10, 20 and 40 items), number of categories (3, 4 and 5)
      and sample size (500, 1000 and 2000 examinees). Power and Type I error rates are
      described. Chi-square statistics based on posterior probabilities showed the best
      performance, especially with larger sample sizes and shorter test lengths.

PMID- 19861113
TI  - [Psychometric properties of the Vancouver Obsessional Compulsive Inventory (VOCI)
      in two non-clinical Spanish samples].
AB  - In this study, the factorial structure and psychometric properties of the
      Vancouver Obsessional Compulsive Inventory (VOCI) were examined in two non
      clinical Spanish samples. An exploratory factor analysis replicated the original
      six-factor structure. Moreover, results showed that the Spanish VOCI is a
      reliable measure. Also, this version had good convergent validity with other
      obsessive-compulsive symptom measures and with an instrument that assess beliefs
      that are relevant to the obsessive-compulsive disorder. Lastly, this version
      showed good divergent validity with measures of depression, anxiety and worries.

PMID- 19861114
TI  - [Is there life beyond SPSS? Discover R].
AB  - R is a GNU statistical and programming environment with very high graphical
      capabilities. It is very powerful for research purposes, but it is also an
      exceptional tool for teaching. R is composed of more than 1400 packages that
      allow using it for simple statistics and applying the most complex and most
      recent formal models. Using graphical interfaces like the Rcommander package,
      permits working in user-friendly environments which are similar to the graphical
      environment used by SPSS. This last characteristic allows non-statisticians to
      overcome the obstacle of accessibility, and it makes R the best tool for
      teaching. Is there anything better? Open, free, affordable, accessible and always
      on the cutting edge.

PMID- 19861115
TI  - Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of
      infection.
AB  - In felids, feline leukemia virus (FeLV) infection results in a variety of
      outcomes that range from abortive (virus readily eliminated and never detectable)
      to progressive infection (persistent viremia and viral shedding). Recently, a
      novel outcome was postulated for low FeLV infectious doses. Naive cats exposed to
      faeces of persistently infected cats seroconverted, indicating infection, but
      remained negative for provirus and p27 antigen in blood. FeLV provirus was found
      in some tissues but not in the bone marrow, infection of which is usually
      considered a necessary stage for disease progression. To investigate the impact
      of low FeLV doses on young cats and to test the hypothesis that low dose exposure
      may lead to an unknown pathogenesis of infection without involvement of the bone
      marrow, 21 cats were infected oronasally with variable viral doses. Blood p27,
      proviral and viral loads were followed until week 20 post-infection. Tissue
      proviral loads were determined as well. The immune response was monitored by
      measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated
      cell membrane antigen (FOCMA) assay. One cat showed regressive infection
      (transient antigenemia, persistent provirus-positivity, and seroconversion) with
      provirus only found in some organs at sacrifice. In 7 of the 20 remaining cats
      FOCMA assay positivity was the only sign of infection, while all other tests were
      negative. Overall, the results show that FeLV low dose exposure can result in
      seroconversion during a presumed abortive infection. Therefore, commonly used
      detection methods do not detect all FeLV-infected animals, possibly leading to an
      underestimation of the prevalence of infection.

PMID- 19861116
TI  - Epithelial-mesenchymal transition with expression of SNAI1-induced
      chemoresistance in colorectal cancer.
AB  - BACKGROUND: Previous reports have demonstrated that SNAI1 plays a role in
      epithelial-mesenchymal transition (EMT) through the suppression of CDH1. Its role
      in the pathology and regulation of EMT expression to chemoresistance in
      colorectal cancer (CRC) has not yet been fully elucidated. METHODS:
      Immunohistochemistry was performed to evaluate the expression of Snai1 protein in
      30 primary CRC samples. The biological significance of Snai1 expression was
      studied by induction of the wild-type (WT) and mutant SNAI1 gene in CRC SW480
      cells. RESULTS: Examination of 20 surgical specimens of CRC indicated that Snai1
      protein expression was localized outer regions of invasive tumors. Introduction
      of phosphorylation-defective active EMT forms, SNAI1-6SA and SNAI1-8SA, caused
      downregulation of CDH1 and upregulation of VIM compared with SNAI1-WT and the
      negative control (NC). Chemoresistance to 5-fluorouracil (IC50) was higher in
      SNAI1-6SA and SNAI1-8SA transfectants compared with SNAI1-WT and NC. All the
      above results were significantly different. CONCLUSION: The present study
      demonstrated that Snai1 plays a role in CRC invasion through phosphorylation,
      suggesting a plausible mechanism for overcoming chemoresistance that will lead to
      the development of effective treatments for CRC.

PMID- 19861117
TI  - The PGC-1alpha-dependent pathway of mitochondrial biogenesis is upregulated in
      type I endometrial cancer.
AB  - PGC-1alpha-dependent pathway of mitochondrial biogenesis was investigated for the
      first time in type I endometrial cancer and in normal endometrium. In cancer
      endometrial tissue the citrate synthase activity, the mitochondrial DNA content
      and the TFAM level were found doubled compared to control endometrial tissue.
      Moreover, a 1.6- and 1.8-fold increase, respectively, of NRF-1 and PGG-1alpha
      expression was found. This study demonstrates, for the first time, that the
      increased mitochondrial biogenesis in type I endometrial cancer is associated to
      the upregulation of PGC-1alpha signalling pathway.

PMID- 19861118
TI  - Antibody-mediated synergy and interference in the neutralization of SARS-CoV at
      an epitope cluster on the spike protein.
AB  - Incomplete neutralization of virus, especially when it occurs in the presence of
      excess neutralizing antibody, represents a biological phenomenon that impacts
      greatly on antibody-mediated immune prophylaxis of viral infection and on
      successful vaccine design. To understand the mechanism by which a virus escapes
      from antibody-mediated neutralization, we have investigated the interactions of
      non-neutralizing and neutralizing antibodies at an epitope cluster on the spike
      protein of severe acute respiratory syndrome coronavirus (SARS-CoV). The epitope
      cluster was mapped at the C-terminus of the spike protein; it consists of
      structurally intertwined epitopes recognized by two neutralizing monoclonal
      antibodies (mAbs), 341C and 540C, and a non-neutralizing mAb, 240C. While mAb
      341C binds to a mostly linear epitope composed of residues (507)PAT(509) and
      V(349), mAb 240C binds to an epitope that partially overlaps the former by at
      least two residues (P(507) and A(508)). The epitope corresponding to mAb 540C is
      a conformational one, involving residues L(504) and N(505). In neutralization
      assays, non-neutralizing 240C disrupted virus neutralization by mAb 341C and/or
      mAb 540C, whereas a combination of mAbs 341C and 540C blocked virus infectivity
      synergistically. These findings indicate that the epitope cluster on the spike
      protein may serve as an evolutionarily conserved platform at which a dynamic
      interplay between neutralizing and non-neutralizing antibodies occurs, thereby
      determining the outcome of SARS-CoV infection.

PMID- 19861119
TI  - NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid
      signaling via up-regulation of fatty acid binding protein 5.
AB  - The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult
      nervous system and is also induced as an immediate early gene in a variety of
      cell types. In silico analysis of human promoters identified fatty acid binding
      protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated
      PPARbeta/delta signaling, as a potential Nurr1 target gene. Nurr1 has previously
      been implicated in retinoid signaling via its heterodimerization partner RXR.
      Since NRs are commonly involved in cross-regulatory control we decided to further
      investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression
      was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown
      to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct
      downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic
      acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation
      of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPARbeta/delta and
      DHA-induced activation of RXR. We also found that other members of the NR4A
      orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs
      can influence signaling events of other NRs via control of FABP5 expression
      levels.

PMID- 19861120
TI  - Can the fluorescence of green fluorescent protein chromophore be related directly
      to the nativity of protein structure?
AB  - In studies of green fluorescence protein (GFP) or other proteins with the use of
      GFP as a marker, the fluorescence of GFP is for the most part related directly to
      the nativity of its structure. Naturally, such a relation does exist since the
      chromophore of this protein is formed autocatalytically only just after GFP
      acquires its native structure. However, the fluorescence method may not yield
      reliable information on protein structure when studying renaturation and
      denaturation of this protein (with the formed chromophore). Using proteolysis,
      denaturant gradient gel electrophoresis and circular dichroism, we demonstrate
      herein that at major disturbances of the native structure of protein GFP-cycle3
      the intensity of fluorescence of its chromophore can change insignificantly. In
      other words, the chromophore fluorescence does not reliably mirror alterations in
      protein structure. Since the main conclusions of this study are especially
      qualitative, it can be suggested that during renaturation/denaturation of wild
      type GFP and its "multicolored" mutants their fluorescence is also not always
      associated with the changes in the structure of these proteins.

PMID- 19861121
TI  - A novel ultrasound-based method to evaluate hemostatic function of whole blood.
AB  - BACKGROUND: Unregulated hemostasis represents a leading cause of mortality and
      morbidity in the developed world. Being able to recognize and quantify defects of
      the hemostatic process is critical to reduce mortality and implement appropriate
      treatment. METHODS: We describe a novel ultrasound-based technology, named
      sonorheometry, which can assess hemostasis function from a small sample of blood.
      Sonorheometry uses the phenomenon of acoustic radiation force to measure the
      dynamic changes in blood viscoelasticity during clot formation and clot
      dissolution. We performed in vitro experiments using whole blood samples of 1 ml
      to demonstrate that sonorheometry is indicative of hemostatic functions that
      depend on plasma coagulation factors, platelets, and plasma fibrinolytic factors.
      RESULTS: Sonorheometry measurements show titration effects to compounds known to
      alter the coagulation factors (GPRP peptide, 0 to 8 mmol/l), platelets
      (abciximab, 0 to 12 microg/ml), and fibrinolytic factors (urokinase, 0 to 200 U).
      Repeated measurements of blood samples from the same subjects yielded
      reproducibility errors on the order of 5%. CONCLUSIONS: These data indicate that
      sonorheometry accurately quantifies the functional role of the components of
      hemostasis in vitro.

PMID- 19861122
TI  - Urine sediment analysis: Analytical and diagnostic performance of sediMAX - a new
      automated microscopy image-based urine sediment analyser.
AB  - BACKGROUND: We evaluated the analytical and diagnostic performance of sediMAX (77
      Elektronika, Budapest, Hungary), a new automated microscopy image-based urine
      sediment analyser (which in some countries is also called Urised) in comparison
      with visual phase-contrast microscopy. METHODS: Precision, linearity, carry-over
      and method comparison were carried out according to well-established guidelines.
      The diagnostic performance with respect to visual phase-contrast microscopy was
      evaluated with results from two centres (n(1)=910, n(2)=1233). Uncentrifuged
      urine samples were used in visual microscopy in centre 1, while urine sediments
      were used in centre 2. RESULTS: Within-run precision for RBC was 17.8% and 6.7%
      at 18xE6 RBC/L and 447xE6 RBC/L respectively and for WBC it was 17% and 4.4% at
      4xE6 WBC/L and 258xE6/L respectively. Between-run imprecision for RBC was 14.7%
      for 30xE6/L and 7.2% for 283xE6/L. For WBC it was 5.4% at 25xE6/L and 3% at
      166xE6/L. In both studies areas under ROC curves (AUC) were 80-90% for RBC, WBC,
      squamous epithelial cells, yeast and calcium-oxalate crystals. For non-squamous
      epithelial cells and pathological and hyaline casts the AUC ranged 73-74%. There
      was no carry-over. CONCLUSIONS: The sediMAX is well able to count and identify
      RBC, WBC, squamous epithelial cells, yeast, bacteria and calcium-oxalate
      crystals. Recognition of pathological casts and non-squamous epithelial cells is
      adequate but needs to be improved.

PMID- 19861123
TI  - Confocal microscopic findings of cysteine protease calpain in Plasmodium
      falciparum.
AB  - Pf-calpain, a cysteine protease of Plasmodium falciparum, is believed to be one
      of the central mediators for essential parasitic activity. However, the roles of
      calpain on parasitic activity have not been determined in P. falciparum. In the
      present study, the localization of Pf-calpain was investigated using polyclonal
      antibodies (anti-Pf-calpain antibody A and B) against peptides that distinguished
      it from human calpain-7 and rat calpain-10 protein. Recombinant Pf-calpain (rPf
      calpain) was identified as a 46 kDa protein using an anti-Pf-calpain antibody A,
      which can recognize the Pf-calpain binding site. Confocal microscopy revealed
      calpain within cytoplasmic localized parasites in the erythrocytic cycle. The
      findings suggested that the expression of Pf-calpain would be proportional to all
      different parasites in the erythrocytic cycle. On the other hand, anti-human
      calpain-7 antibody detected Pf-calpain in schizonts, and the immunofluorescence
      was stronger than with anti-rat calpain-10 antibody. However, the antibodies
      reacted with calpains in human red blood cells. These results show that anti-Pf
      calpain antibody A and B specifically recognize only Pf-calpain. Taken together,
      the results suggest that Pf-calpain is expressed in all erythrocytic stages. In
      particular, the expression of Pf-calpain is increased much more when the late
      ring matures into the early trophozoite. Moreover, anti-Pf-calpain antibody A and
      B against synthetic peptides of the catalytic domain of Pf-calpain are useful to
      specifically detect Pf-calpain in all erythrocytic stages, while human and rat
      calpain antibody are not useful.

PMID- 19861124
TI  - Fasciola gigantica: Parasitological and scanning electron microscopy study of the
      in vitro effects of ivermectin and/or artemether.
AB  - OBJECTIVE: To evaluate the in vitro effects of different concentrations of
      ivermectin and/or artemether on Fasciolagigantica worms and to study the
      parasitological changes and tegumental alterations using scanning electron
      microscopy (SEM). METHODS: Fasciola gigantica worms were incubated in vitro for
      24 and 48 h with three concentrations of either ivermectin or artemether (10, 20
      and 50 microg/ml) or both in half concentration of either (5, 10 and 25
      microg/ml). RESULTS: Exposure of Fasciola worms to 25+25 microg/ml of combined
      drug regimens or to 50 microg/ml of either ivermectin or artemether for 48 h led
      to 100%, 41.7% and 75% worm killing which were accompanied by a significant
      reduction in egg laying capacity and significant increase in dead eggs maximally
      recorded in combined drug regimens. SEM of the flukes incubated for 48 h with
      combined drug regimens showed maximal tegumental disruption with swelling of the
      worm body, roughness, blebbing, sloughing and complete loss of spines. Disruption
      to the tegument of the flukes induced by artemether was more than that of
      ivermectin. CONCLUSIONS: Artemether alone or combined with ivermectin in half
      doses had potent fasciocidal activities. Besides, half doses of combined drug
      regimens had higher ovicidal effects than each drug alone. In vivo studies are
      recommended to explore the efficacy of combined regimens against Fasciola
      infection.

PMID- 19861125
TI  - Binding of epigallocatechin-3-gallate to transthyretin modulates its
      amyloidogenicity.
AB  - More than 100 transthyretin (TTR) variants are associated with hereditary
      amyloidosis. Approaches for TTR amyloidosis that interfere with any step of the
      cascade of events leading to fibril formation have therapeutic potential. In this
      study we tested (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin
      of green tea, as an inhibitor of TTR amyloid formation. We demonstrate that EGCG
      binds to TTR "in vitro" and "ex vivo" and that EGCG inhibits TTR aggregation "in
      vitro" and in a cell culture system. These findings together with the low
      toxicity of the compound raise the possibility of using EGCG in a therapeutic
      approach for familial amyloidotic polyneuropathy, the most frequent form of
      hereditary TTR amyloidosis.

PMID- 19861126
TI  - Structure and function of mitochondrial carriers - role of the transmembrane
      helix P and G residues in the gating and transport mechanism.
AB  - To date, 22 mitochondrial carrier subfamilies have been functionally identified
      based on substrate specificity. Structural, functional and bioinformatics studies
      have pointed to the existence in the mitochondrial carrier superfamily of a
      substrate-binding site in the internal carrier cavity, of two salt-bridge
      networks or gates that close the cavity alternatively on the matrix or the
      cytosolic side of the membrane, and of conserved prolines and glycines in the
      transmembrane alpha-helices. The significance of these properties in the
      structural changes occurring during the catalytic substrate translocation cycle
      are discussed within the context of a transport mechanism model. Most
      experimentally produced and disease-causing missense mutations concern carrier
      regions corresponding to the substrate-binding site, the two gates and the
      conserved prolines and glycines.

PMID- 19861127
TI  - Intact intracellular tail is critical for proper functioning of the tumor
      associated, hypoxia-regulated carbonic anhydrase IX.
AB  - Carbonic anhydrase IX (CA IX) is a tumor-associated, hypoxia-induced enzyme
      involved in pH regulation and cell adhesion. Its catalytically active ectodomain
      (ECD) is linked to a transmembrane region and a short intracellular (IC) tail.
      Removal of the IC tail causes intracellular localization of CA IX. Mutations of
      basic amino acids within IC do not perturb the membrane position, but reduce
      shedding of the CA IX ectodomain as well as CA IX-mediated cell dissociation.
      Moreover, they abolish the CA IX capacity to acidify extracellular pH (pHe) and
      bind CA IX-selective sulfonamide inhibitor in hypoxia. These findings provide the
      first evidence for the critical contribution of the IC tail to the proper
      functioning of CA IX.

PMID- 19861128
TI  - Aging of hepatitis C virus (HCV)-infected persons in the United States: a
      multiple cohort model of HCV prevalence and disease progression.
AB  - BACKGROUND & AIMS: The prevalence of chronic hepatitis C (CH-C) remains high and
      the complications of infection are common. Our goal was to project the future
      prevalence of CH-C and its complications. METHODS: We developed a multicohort
      natural history model to overcome limitations of previous models for predicting
      disease outcomes and benefits of therapy. RESULTS: Prevalence of CH-C peaked in
      2001 at 3.6 million. Fibrosis progression was inversely related to age at
      infection, so cirrhosis and its complications were most common after the age of
      60 years, regardless of when infection occurred. The proportion of CH-C with
      cirrhosis is projected to reach 25% in 2010 and 45% in 2030, although the total
      number with cirrhosis will peak at 1.0 million (30.5% higher than the current
      level) in 2020 and then decline. Hepatic decompensation and liver cancer will
      continue to increase for another 10 to 13 years. Treatment of all infected
      patients in 2010 could reduce risk of cirrhosis, decompensation, cancer, and
      liver-related deaths by 16%, 42%, 31%, and 36% by 2020, given current response
      rates to antiviral therapy. CONCLUSIONS: Prevalence of hepatitis C cirrhosis and
      its complications will continue to increase through the next decade and will
      mostly affect those older than 60 years of age. Current treatment patterns will
      have little effect on these complications, but wider application of antiviral
      treatment and better responses with new agents could significantly reduce the
      impact of this disease in coming years.

PMID- 19861129
TI  - Multiscale determinants of parasite abundance: a quantitative hierarchical
      approach for coral reef fishes.
AB  - During recent decades, there have been numerous attempts to identify the key
      determinants of parasite communities and several influential variables have been
      clarified at either infra-, component or compound community scales. However, in
      view of the possible complexity of interactions among determinants, the commonly
      used exploratory and statistical modelling techniques have often failed to find
      meaningful ecological patterns from such data. Moreover, quantitative assessments
      of factors structuring species richness, abundance, community structure and
      species associations in parasite communities remain elusive. Recently, because
      they are ideally suited for the analysis of complex and highly interactive data,
      there has been increasing interest in the use of classification and regression
      tree analyses in several ecological fields. To date, such approaches have never
      been used by parasitologists for field data. This study aims to both introduce
      and illustrate the use of multivariate regression trees in order to investigate
      the determinants of parasite abundance in a multi-scale quantitative context. To
      do this, we used new field epidemiological data from 1489 coral reef fishes
      collected around two islands in French Polynesia. We evaluated the relative
      effect and interactions of several host traits and environmental factors on the
      abundance of metazoan parasite assemblage at several scales and assessed the
      impact of major factors on each parasite taxon. Our results suggest that the
      islands sampled, the host species and host size are equal predictors of parasite
      abundance at a global scale, whereas other factors proved to be significant
      predictors of a local pattern, depending on host family. We also discuss the
      potential use of regression trees for parasitologists as both an explorative and
      a promising predictive tool.

PMID- 19861130
TI  - Identification of NbME MITE families: potential molecular markers in the
      microsporidia Nosema bombycis.
AB  - Six novel families of miniature inverted-repeat transposable elements (MITEs)
      were characterized in the microsporidia Nosema bombycis and were named NbMEs. The
      structural characteristics and the distribution of NbME copies in the N. bombycis
      genome were investigated, and it was found that portions of NbMEs are associated
      with gene sections. Potential molecular markers for various N. bombycis strains
      were identified in this study through utilization of the MITE-AFLP technique.
      Three distinct pathogenic isolates collected from different areas were
      distinguished, and polymorphisms were detected using the NbME5 marker, thereby
      establishing this NbME as a potential marker for studying isolate variation in N.
      bombycis.

PMID- 19861131
TI  - Successional state dynamics: a novel approach to modeling nonequilibrium foodweb
      dynamics.
AB  - Communities and ecosystems are often far from equilibrium, but our understanding
      of nonequilibrium dynamics has been hampered by a paucity of analytical tools.
      Here I describe a novel approach to modeling seasonally forced food webs, called
      "successional state dynamics" (SSD). It is applicable to communities where
      species dynamics are fast relative to the external forcing, such as plankton and
      other microbes, diseases, and some insect communities. The approach treats
      succession as a series of state transitions driven by both the internal dynamics
      of species interactions and external forcing. First, I motivate the approach with
      numerical solutions of a seasonally forced predator-prey model. Second, I
      describe how to set up and analyze an SSD model. Finally, I apply the techniques
      to three additional models of two-species interactions: resource competition (r-K
      selection), facilitation, and flip-flop competition (where the competitive
      hierarchy alternates over time). This approach allows easy and thorough
      exploration of how dynamics depend on the environmental forcing regime, and
      uncovers unexpected phenomena such as multiple stable annual trajectories and
      year-to-year irregularity in successional trajectories (chaos).

PMID- 19861132
TI  - Modeling spatiotemporal dynamics of vole populations in Europe and America.
AB  - The mathematical models proposed and studied in the present paper provide a
      unified framework to understand complex dynamical patterns in vole populations in
      Europe and North America. We have extended the well-known model provided by
      Hanski and Turchin by incorporating the diffusion term and spatial heterogeneity
      and performed several mathematical and numerical analyses to explore the dynamics
      in space and time of the model. These models successfully predicted the observed
      rodent dynamics in these regions. An attempt has been made to bridge the gap
      between the field and theoretical studies carried out by Turchin and Hanski
      (1997) and Turchin and Ellner (2000). Simulation experiments, mainly two
      dimensional parameter scans, show the importance of spatial heterogeneity in
      order to understand the poorly understood fluctuations in population densities of
      voles in Fennoscandia and Northern America. This study shed new light upon the
      dynamics of voles in these regions. The nonlinear analysis of vole data suggests
      that the dynamical shift is from stability to chaos. Diffusion driven model
      systems predict a new type of dynamics not yet observed in the field studies of
      vole populations carried out so far. This has been termed as chaotic in time and
      regular in space (CTRS). We observed CTRS dynamics in several simulation
      experiments. This directs us to expect that dynamics of this animal would be de
      correlated in time and simultaneously mass extinctions might be possible at many
      spatial locations.

PMID- 19861133
TI  - Stochastic eco-epidemiological model of dengue disease transmission by Aedes
      aegypti mosquito.
AB  - We present a stochastic dynamical model for the transmission of dengue that takes
      into account seasonal and spatial dynamics of the vector Aedes aegypti. It
      describes disease dynamics triggered by the arrival of infected people in a city.
      We show that the probability of an epidemic outbreak depends on seasonal
      variation in temperature and on the availability of breeding sites. We also show
      that the arrival date of an infected human in a susceptible population
      dramatically affects the distribution of the final size of epidemics and that
      early outbreaks have a low probability. However, early outbreaks are likely to
      produce large epidemics because they have a longer time to evolve before the
      winter extinction of vectors. Our model could be used to estimate the risk and
      final size of epidemic outbreaks in regions with seasonal climatic variations.

PMID- 19861134
TI  - Inhibition of masked primes as revealed by saccade curvature.
AB  - In masked priming, responses are often speeded when primes are similar to targets
      ('positive compatibility effect'). However, sometimes similarity of prime and
      target impairs responses ('negative compatibility effect'). A similar distinction
      has been found for the curvature of saccade trajectories. Here, we test whether
      the same inhibition processes are involved in the two phenomena, by directly
      comparing response times and saccade curvature within the same masked priming
      paradigm. Interestingly, we found a dissociation between the directions of masked
      priming and saccade curvature, which could indicate that multiple types of
      inhibition are involved in the suppression of unwanted responses.

PMID- 19861135
TI  - Specific growth rate dependent transcriptome profiling of Escherichia coli K12
      MG1655 in accelerostat cultures.
AB  - Specific growth rate dependent gene expression changes of Escherichia coli K12
      MG1655 were studied by microarray and real-time PCR analyses. The bacteria were
      cultivated on glucose limited minimal medium using the accelerostat method (A
      stat) where starting from steady state conditions (chemostat culture) dilution
      rate is constantly increased. At specific growth rate (mu) 0.47h(-1), E. coli had
      focused its metabolism to glucose utilization by down-regulation of alternative
      substrate transporters expression compared to mu=0.3h(-1). It was found that
      acetic acid accumulation began at mu=0.34+/-0.01h(-1) and two acetate synthesis
      pathways - phosphotransacetylase-acetate kinase (pta-ackA) and pyruvate oxidase
      (poxB) - contributed to the synthesis at the beginning of overflow metabolism,
      i.e. onset of acetate excretion. On the other hand, poxB, pta and ackA expression
      patterns suggest that pyruvate oxidase may be the only enzyme synthesizing
      acetate at mu=0.47h(-1). Loss of glucose and acetate co-utilization represented
      by down-regulation of acs-yjcH-actP operon between specific growth rates 0.3
      0.42h(-1) and acetic acid accumulation from mu=0.34+/-0.01h(-1) allows one to
      surmise that the acetate utilization operon expression might play an important
      role in overflow metabolism.

PMID- 19861136
TI  - Isolation of antigen-binding camelid heavy chain antibody fragments (nanobodies)
      from an immune library displayed on the surface of Pichia pastoris.
AB  - Yeast surface display is an efficient tool for isolating and engineering antibody
      fragments, both scFv and Fab. We describe the use of protein display on Pichia
      pastoris for the rapid selection of camelid antibodies composed only of heavy
      chains (nanobodies) from a library derived from a llama immunized with Green
      Fluorescent Protein. The library of nanobody-coding sequences was fused to the C
      terminal part of the Saccharomyces cerevisiae alpha-agglutinin gene (SAG1) and
      expressed in glycoengineered P. pastoris. A high efficiency transformation
      protocol yielded a library of 5x10(7) clones. About 80% of the clones strongly
      expressed the nanobody fusion. Nanobody-displaying clones were rapidly enriched
      by fluorescence activated cell sorting (FACS), and GFP-specific nanobody
      displaying clones were isolated and equilibrium dissociation constants (K(d))
      determined. This technology for displaying protein libraries on P. pastoris
      enables the isolation and engineering of antibody-derived molecules in a robust
      eukaryotic expression host.

PMID- 19861137
TI  - An accurate normalization strategy for RT-qPCR in Hypocrea jecorina (Trichoderma
      reesei).
AB  - Hypocrea jecorina is an important, filamentous fungus due to its effective
      production of hydrolytic enzymes. Gene expression studies provide deeper insight
      into environment sensing and cellular response mechanisms. Reverse transcription
      quantitative PCR is a gene-specific and powerful tool to measure even minor
      changes in mRNA composition. An accurate normalization strategy is absolutely
      necessary for appropriate interpretation of reverse transcription-quantitative
      PCR results. One frequently applied strategy is the usage of a reference gene.
      Adequate reference genes for Hypocrea have not been published so far. By using
      the NormFinder and geNorm softwares, we evaluated the most stable genes amongst
      six potential reference genes in 34 samples from diverse cultivation conditions.
      Under those experimental conditions, sar1 encoding for a small GTPase was found
      to be the most stable gene, whereas act encoding for actin was not amongst the
      best validated ones. The influence of the reference system on the expression data
      is demonstrated by analysis of two target genes, encoding for the Xylanase
      regulator 1 and for Xylanase II. We further validated obtained xylanase 2
      transcription rates with the corresponding enzyme activity.

PMID- 19861138
TI  - Enhanced expression and activity yields of Clostridium thermocellum xylanases
      without non-catalytic domains.
AB  - Two major xylanase components, XynC and XynZ from the anaerobic thermophilic
      bacterium, Clostridium thermocellum cellulosome were cloned and expressed with
      and without non-catalytic domains in E. coli. Two constructs of XynC, one with
      its cellulose binding domain and the catalytic domain (pXynC-BC) and the other
      with only the catalytic domain (pXynC-C) were produced. For XynZ the constructs
      produced were pXynZ-BDC, which included the dockerin domain, and pXynZ-C, which
      did not. E. coli cells transformed with pXynC-BC or pXynZ-BDC gave xylanase
      expression of 30% and 25% total cell proteins, respectively. Transformation of E.
      coli cells with the constructs carrying only the catalytic domains gave
      expression levels of approximately 45% in each case. The specific activities of
      XynC with and without the non-catalytic domains were similar, but for XynZ the
      specific activity of the enzyme without the non-catalytic domains was
      approximately 5-fold greater than that of the intact enzyme. The total activity
      increased from 1925Ul(-1)OD(600)(-1) for XynC-BC to 3050Ul(-1)OD(600)(-1) for
      XynC-C. However, the overall increase in activity was approximately 9-fold higher
      for XynZ-C (32,900Ul(-1)OD(600)(-1)) versus XynZ-BDC (3665Ul(-1)OD(600)(-1)).
      Both the enzymes with and without non-catalytic domains were found to be quite
      stable over a broad pH range (pH 4-9). XynZ-C was more thermostable than XynZ-BDC
      as it retained 87% of xylanase activity when incubated at 70 degrees C for 2h as
      compared to 42% for XynZ-BDC. However, XynC-BC retained 70% activity on
      incubation at 70 degrees C for 2h but XynC-C lost all activity under the same
      conditions. K(m) values for XynC-BC and XynC-C determined on soluble xylan were
      3.1 and 3.6 mg ml(-1), respectively, whereas these values for XynZ-BDC and XynZ-C
      were 33.3 and 15.4 mg ml(-1), respectively. Thus the production of xylanase
      activity by expressing only the catalytic domains of XynC and XynZ is
      significantly enhanced.

PMID- 19861139
TI  - Displaying non-natural, functional molecules on yeast surfaces via biotin
      streptavidin interaction.
AB  - Here we expand the yeast cell surface display system to display non-natural,
      functional molecules. The short biotin acceptor peptide (BAP) sequence of biotin
      ligase from E. coli (BirA) was genetically introduced to the N-terminus of the
      anchor protein, Flo428. Through co-expression of BAP-fused Flo428 with BirA,
      biotinylated BAP could be displayed on the yeast cell surface. Subsequent
      addition of streptavidin-FITC resulted in the display of streptavidin-FITC, and,
      the display of biotin-FITC was successful using streptavidin as a linker. Our
      strategy provides a powerful tool for displaying functional molecules on yeast
      cell surfaces.

PMID- 19861140
TI  - Sequential administration with oxaliplatin-containing PEG-coated cationic
      liposomes promotes a significant delivery of subsequent dose into murine solid
      tumor.
AB  - Recently, we designed a PEG-coated cationic liposome to achieve dual targeting
      delivery of l-OHP to both tumor endothelial cells and tumor cells in a solid
      tumor. The targeted liposomal l-OHP formulation showed an efficient antitumor
      activity in a murine tumor model after three sequential liposomal l-OHP
      injections. This led us to assume that prior dosing with liposomes might enhance
      the intra-tumoral accumulation of a subsequent dose, and hence improve the
      therapeutic efficacy of entrapped l-OHP. The present study shows that while a
      single liposomal l-OHP injection does not enhance tumor accumulation of
      subsequent test-PEG-coated cationic liposomes, two sequential injections of
      liposomal l-OHP do. Cumulative cytotoxic effects of l-OHP delivered by PEG-coated
      cationic liposomes led to deep diffusion of a subsequent dose of liposomal l-OHP
      in solid tumor presumably as a result of the enlarged intra-tumoral interstitial
      space. Our study suggests that sequential injections of a targeted liposomal
      anticancer drug is of significant clinical and practical importance in enhancing
      the delivery of adequate quantities of anticancer agents into intractable solid
      tumors, and thereby may achieve a significant anticancer efficacy.

PMID- 19861141
TI  - Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic
      lipids for improving intracellular drug delivery in vitro and in vivo.
AB  - We developed pH-responsive liposomes containing synthetic glutamic acid-based
      zwitterionic lipids and evaluated their properties both in vitro and in vivo with
      the aim of constructing an efficient liposome-based systemic drug delivery
      system. The glutamic acid-based lipids; 1,5-dihexadecyl N-glutamyl-L-glutamate
      (L1) and 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (L2) were synthesized
      as a pH-responsive component of liposomes that respond to endosomal pH. The zeta
      potential of liposomes containing L1 or L2 was positive when the solution pH was
      below 4.6 or 5.6, respectively, but negative at higher pH values. The pH
      responsive liposomes showed improved fusogenic potential to an endosome-mimicking
      anionic membrane at acidic pH, where the zeta potential of the liposomes was
      positive. We then prepared doxorubicin (DOX)-encapsulating liposomes containing
      L1 or L2, and clarified by confocal microscopic studies that the contents were
      rapidly transferred into both the cytoplasm and nucleus. Release of DOX from the
      endosomes mediated by the pH-responsive liposomes dramatically inhibited cancer
      cell growth. The L2-liposomes were slightly more effective than L1-liposomes as a
      drug delivery system. Intravenously injected L2-liposomes displayed blood
      persistence comparable to that of conventional phospholipid (PC)-based liposomes.
      Indeed, the antitumor efficacy of L2-liposomes was higher than that of PC-based
      liposomes against a xenograft breast cancer tumor in vivo. Thus, the high
      performance of L2-liposomes results from both efficient intracellular drug
      delivery and comparable blood persistence in comparison with the conventional PC
      based liposomes in vitro and in vivo.

PMID- 19861142
TI  - Chitosan-based systems for molecular imaging.
AB  - Molecular imaging enables the non-invasive assessment of biological and
      biochemical processes in living subjects. Such technologies therefore have the
      potential to enhance our understanding of disease and drug activity during
      preclinical and clinical drug development. Molecular imaging allows a repetitive
      and non-invasive study of the same living subject using identical or alternative
      biological imaging assays at different time points, thus harnessing the
      statistical power of longitudinal studies, and reducing the number of animals
      required and cost. Chitosan is a hydrophilic and non-antigenic biopolymer and has
      a low toxicity toward mammalian cells. Hence, it has great potential as a
      biomaterial because of its excellent biocompatibility. Conjugated to additional
      materials, chitosan composites result in a new class of biomaterials that possess
      mechanical, physicochemical and functional properties, which have potential for
      use in advanced biomedical imaging applications. The present review will discuss
      the strengths, limitations and challenges of molecular imaging as well as
      applications of chitosan nanoparticles in the field of molecular imaging.

PMID- 19861143
TI  - Description of two novel alleles HLA-Cw*0766 and Cw*0767 identified in a Chinese
      Han individual by sequence-based typing.
AB  - We report two novel HLA-C alleles, Cw*0766, and Cw*0767 identified in a Chinese
      voluntary stem cell donor. This sample was initially found by direct PCR-SBT with
      an inconclusive result. To clarify this unusual SBT result, the PCR product of
      HLA-C gene covering from exon 1-4 was subjected to cloning and haplotype
      sequencing and family study of HLA inheritance consisting of six members were
      confirmed. Novel Cw*0766 allele differs from the closest allele Cw*07020101 by
      single nucleotide change at genomic DNA nt 1651 C>A (codon 206 CTG>ATG) in exon
      4, which results in an amino acid change Leu206Met. Another novel allele Cw*0767
      differs from the closest allele Cw*07020103 by single nucleotide change at
      genomic DNA nt 930 A>T (codon 161 GAG>GTG) in exon 3, which results in an amino
      acid change Glu161Val. Family study demonstrated that the novel Cw*0766 allele
      segregating on an A*2402 B*4001 Cw*0766 DRB1*1202 haplotype was inherited from
      the mother of the propositus, whereas the novel Cw*0767 allele on haplotype
      A*1101 B*0702 Cw*0767 DRB1*0101 was inherited from the father.

PMID- 19861144
TI  - Activating killer cell immunoglobulin-like receptors 3DS1 and 2DS1 protect
      against developing the severe form of recurrent respiratory papillomatosis.
AB  - The polymorphic killer cell immunoglobulin-like receptors (KIR) control natural
      killer (NK) cell response against viral infection and tumor transformation. Here
      we investigated if select KIR genes are associated with recurrent respiratory
      papillomatosis (RRP), a rare disease of the larynx and upper airway caused by
      human papillomaviruses (HPV)-6/11. DNA from 66 RRP patients and 195 healthy
      controls were characterized for KIR and HLA gene polymorphism. Patients lacking
      activating KIR genes 3DS1 and 2DS1 were more common in severe RRP compared with
      mild-moderate RRP (78.8% vs 48.5%, p = 0.019). Further, patients carrying any of
      the known susceptible HLA-DRB1/DQB1 alleles were more frequently negative for
      KIR3DS1 (p = 0.006), KIR2DS1 (p = 0.003) or KIR2DS5 (p = 0.004) compared with
      controls carrying any of these HLA allotypes. Nearly 80% of the patients with
      severe disease were missing the protective HLA-DQB1*0602 allele as well as both
      KIR3DS1 and KIR2DS1 genes. Phenotyping of papilloma-infiltrating mononuclear
      cells revealed an elevated numbers of NK cells and CD57(+)CD4(+) T cells in
      KIR3DS1(-)KIR2DS1(-) patients compared with patients carrying either one or both
      of these KIRs. Our data suggest that NK cells expressing activating receptors
      KIR3DS1 and KIR2DS1 may be necessary to trigger an effective early immune
      response against HPV-infected targets to establish resistance to RRP development.

PMID- 19861145
TI  - Combination of curcumin and green tea catechins prevents dimethylhydrazine
      induced colon carcinogenesis.
AB  - The chemopreventive effects of curcumin and green tea catechins individually and
      in combination on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis were
      studied in male Wister rats following 32 weeks of dietary treatment. The
      incidence, number and size of colorectal cancer were measured. Colorectal
      aberrant crypt foci (ACF) were analyzed by methylene blue staining. Proliferation
      indices and apoptotic indices were determined by PCNA immunostaining and TUNEL
      assay, respectively. The results showed that dietary curcumin, catechins and
      combination administration significantly inhibited the total number of ACF per
      rat. The combination treatment displayed the most potent inhibitory effect, while
      there was no difference of inhibition between curcumin and catechins-treated
      groups. The incidence of colorectal cancer in the treated groups was
      significantly lower than that of positive control group. Compared with the
      positive control group, the proliferation index was significantly decreased and
      the apoptotic index was significantly increased in all treatment groups, while
      the effect of the combination was the greatest among the treated groups. Our
      findings suggest that the combination of curcumin and catechins may produce a
      synergistic colon cancer-preventative effect that would be more potent than each
      of the compounds alone.

PMID- 19861146
TI  - Saliva substitute in combination with high-concentrated fluoride toothpaste:
      effects on demineralised dentin in vitro.
AB  - OBJECTIVES: The aim of this in vitro study was to assess the effects of saliva
      substitutes (modified with respect to calcium, phosphates, and fluorides) in
      combination with a high-concentrated fluoride toothpaste on demineralised dentin.
      METHODS: Before and after demineralisation of bovine dentin specimens (subsurface
      lesions; 37 degrees C, pH 5.0, 5 d), one-quarter of each specimen's surface was
      covered with nail varnish (control of sound/demineralised tissue). Subsequently,
      specimens were exposed to original Saliva natura (saturation with respect to
      octacalciumphosphate [S(OCP)]: 0.03; SN 0), or to three lab-produced Saliva
      natura modifications (S(OCP): 1, 2, and 3; SN 1-3) for 2 and 5 weeks (37 degrees
      C). An aqueous solution (S(OCP): 2.5) served as positive control (PC). Two times
      daily (2min each), Duraphat toothpaste (5000ppmF(-); Colgate)/saliva substitute
      slurry (ratio 1:3) was applied gently. Differences in mineral losses
      (DeltaDeltaZ) and lesion depths (DeltaLD) between values before and after
      exposure were microradiographically evaluated. RESULTS: After both treatment
      periods specimens immersed in SN 0 revealed significantly higher mineral losses
      (lower DeltaDeltaZ values) and lesion depths (lower DeltaLD) compared to PC
      (p<0.05; ANOVA). After 5 weeks, specimens stored in SN 1 and 2 showed
      significantly higher mineral losses compared to PC (p<0.05), while those stored
      in SN 3 showed similar results (p>0.05). No differences in mineral loss could be
      observed between SN 2 and 3 (p>0.05). CONCLUSIONS: Under the conditions of this
      limited protocol, the combination of Saliva natura solutions slightly saturated
      with respect to OCP in combination with a high-concentrated fluoride toothpaste
      enabled remineralisation of dentin in vitro.

PMID- 19861147
TI  - Does conscious intention to perform a motor act depend on slow cardiovascular
      rhythms?
AB  - Slow oscillations around 0.1 Hz are characteristic features of both the
      cardiovascular and central nervous systems. Such oscillation have been reported,
      e.g. in blood pressure, heart rate, EEG and brain oxygenation. Hence, conscious
      intention of a motor act may occur only as a result of brain activity changes in
      frontal and related brain areas, or might be entrained by slow oscillations in
      the blood pressure. Twenty-six subjects were asked to perform voluntary, self
      paced (at free will) brisk finger movements. Some subjects performed self-paced
      movements in relatively periodic intervals of around 10s at the decreasing slope
      of the slow 0.1-Hz blood pressure oscillation. Our study reveals the first time
      that self-paced movements, at least in some subjects, do not stem from "free
      will" based on brain activity alone, but are influenced by slow blood pressure
      oscillations.

PMID- 19861148
TI  - Short-term exposure to ethanol causes a differential response between nerve
      growth factor and brain-derived neurotrophic factor ligand/receptor systems in
      the mouse cerebellum.
AB  - Alcohol ingestion affects both neuropsychological and motor functions. We
      hypothesized that one of the key factors involved in such functions are
      neurotrophins and their receptors. We have therefore examined the effects of
      short-term ethanol exposure on the mRNA expression and protein levels of
      neurotrophin ligands and receptors in the cerebellum using real-time RT-PCR and
      Western blotting techniques. Male BALB/C mice were fed a liquid diet containing
      5% (v/v) ethanol. The pair-fed control mice were fed an identical liquid diet
      except that sucrose was substituted isocalorically for ethanol. The cerebellum of
      mice exhibiting intoxication signs of stage 1 or 2 were used in the present
      study. We found that exposure to ethanol resulted in elevated levels of nerve
      growth factor (NGF) and TrkA mRNA expression but a decreased level of brain
      derived neurotrophic factor (BDNF) mRNA expression. The expression of TrkB and
      p73 mRNA was unchanged. Changes in the level of these proteins were found to
      mirror these mRNA expression levels. We conclude that exposure to ethanol for a
      short period can cause a differential responsive in the various neurotrophin
      ligand/receptor systems. The functional consequences of these changes are unknown
      at present.

PMID- 19861150
TI  - The glutamate-based genetic immune hypothesis in obsessive-compulsive disorder.
      An integrative approach from genes to symptoms.
AB  - Recent advances in multiple areas of research have contributed to the
      identification of several pathophysiological factors underlying obsessive
      compulsive disorder (OCD). In particular, the glutamate transporter gene SLC1A1
      has been associated with the diagnosis of OCD. Immunological and infectious
      studies have reported alterations of the immune system and the presence of immune
      complexes directed against the Borna disease virus in OCD patients. In addition,
      neuroimaging of OCD patients has demonstrated abnormalities in the anterior
      cingulate cortex, orbitofrontal cortex, thalamus, and the basal ganglia.
      Neuropsychological assessments have found several cognitive disruptions that have
      been identified in OCD, especially impairments in cognitive flexibility. Here, we
      attempt to bridge the gap between these remarkable findings through several
      previously unpredicted pathophysiological mechanisms. We propose an integrative
      hypothesis that indicates how genetic and environmental factors may contribute to
      the structural and functional alterations of cortico-subcortical circuits,
      leading to the characteristic cognitive disruptions underlying OCD symptoms.

PMID- 19861149
TI  - Cocaine action on peripheral, non-monoamine neural substrates as a trigger of
      electroencephalographic desynchronization and electromyographic activation
      following i.v. administration in freely moving rats.
AB  - Many important physiological, behavioral and subjective effects of i.v. cocaine
      (COC) are exceptionally rapid and transient, suggesting a possible involvement of
      peripheral neural substrates in their triggering. In the present study, we used
      high-speed electroencephalographic (EEG) and electromyographic (EMG) recordings
      (4-s resolution) in freely moving rats to characterize the central
      electrophysiological effects of i.v. COC at low doses within a self
      administration range (0.25-1.0 mg/kg). We found that COC induces rapid, strong,
      and prolonged desynchronization of cortical EEG (decrease in alpha and increase
      in beta and gamma activity) and activation of the neck EMG that begin within 2-6
      s following the start of a 10-s injection; immediate components of both effects
      were dose-independent. The rapid effects of COC were mimicked by i.v. COC
      methiodide (COC-MET), a derivative that cannot cross the blood-brain barrier. At
      equimolar doses (0.33-1.33 mg/kg), COC-MET had equally fast and strong effects on
      EEG and EMG total powers, decreasing alpha and increasing beta and gamma
      activities. Rapid EEG desynchronization and EMG activation was also induced by
      i.v. procaine, a structurally similar, short-acting local anesthetic with
      virtually no effects on monoamine uptake; at equipotential doses (1.25-5.0
      mg/kg), these effects were weaker and shorter in duration than those of COC.
      Surprisingly, i.v. saline injection delivered during slow-wave sleep (but not
      during quiet wakefulness) also induced a transient EEG desynchronization but
      without changes in EMG and motor activity; these effects were significantly
      weaker and much shorter than those induced by all tested drugs. These data
      suggest that in awake animals, i.v. COC induces rapid cortical activation and a
      subsequent motor response via its action on peripheral non-monoamine neural
      elements, involving neural transmission via visceral sensory pathways. By
      providing a rapid neural signal and triggering neural activation, such an action
      might play a crucial role in the sensory effects of COC, thus contributing to the
      learning and development of drug-taking behavior.

PMID- 19861152
TI  - Endothelin evokes distinct calcium transients in neuronal and non-neuronal cells
      of rat olfactory mucosa primary cultures.
AB  - The olfactory system is regulated by several nervous and hormonal factors, and
      there is a growing body of evidence that some of these modulations already take
      place in the olfactory mucosa (OM). We recently suggested that, among others,
      vasoactive peptides might play multifaceted roles in different OM cells. Here we
      studied the effect of the vasoconstrictive peptide endothelin (ET) in the rat OM.
      We identified different components of the ET system both in the olfactory mucosa
      and in long-term primary culture of OM cells, composed of olfactory sensory
      neurons (OSNs) lying on a blend of non-neuronal OM cells (nNCs). We demonstrated
      that ET receptors are differentially expressed on OM cells, and that ET might be
      locally matured by the endothelin-converting enzyme ECE-1 located in OSNs. Using
      calcium imaging, we showed that ET triggers robust dose-dependent Ca(2+)
      responses in most OM cells, which consist of a transient phase, followed, in
      nNCs, by a sustained plateau phase. All transient responses depended on
      intracellular calcium release, while the sustained plateau phase also depended on
      subsequent external calcium entry. Using both pharmacology and spotting lethal
      (sl/sl) mutant rats, lacking functional ET(B) receptors, we finally demonstrated
      that these effects of ET are mediated through ET(B) receptors in OSNs and ET(A)
      receptors in nNCs.The present study therefore identifies endothelin as a potent
      endogenous modulator of the olfactory mucosa; specific endothelin-mediated Ca(2+)
      signals may serve distinct signaling functions, and thereby suggest differential
      functional roles of endothelin in both neuronal and non-neuronal OM cells.

PMID- 19861151
TI  - Escape of intraluminal platelets into brain parenchyma after subarachnoid
      hemorrhage.
AB  - Platelet aggregates are present in parenchymal vessels as early as 10 min after
      experimental subarachnoid hemorrhage (SAH). Structural injury to parenchymal
      vessel walls and depletion of collagen-IV (the major protein of basal lamina)
      occur in a similar time frame. Since platelets upon activation release enzymes
      which can digest collagen-IV, we investigated the topographic relationship
      between platelet aggregates, endothelium, and basal lamina after SAH produced by
      endovascular perforation, using triple immunofluorescence and confocal microscopy
      with deconvolution. The location of platelet aggregates in relation to zymography
      detected active collagenase was also examined. As reported previously, most
      cerebral vessels profiles contained platelets aggregates at 10 min after SAH.
      High-resolution three-dimensional image analysis placed many platelets at the ab
      luminal (basal) side of endothelium at 10 min, and others either within the
      vascular basal lamina or in nearby parenchyma. By 24 h post hemorrhage, large
      numbers of platelets had entered the brain parenchyma. The vascular sites of
      platelet movement were devoid of endothelium and collagen-IV. Collagenase
      activity colocalized with vascular platelet aggregates. Our data demonstrate that
      parenchymal entry of platelets into brain parenchyma begins within minutes after
      hemorrhage. Three-dimensional analysis suggests that platelet aggregates initiate
      or stimulate local disruption of endothelium and destruction of adjacent basal
      lamina after SAH.

PMID- 19861153
TI  - Berberine inhibits adipogenesis in high-fat diet-induced obesity mice.
AB  - Our previous studies illustrated that berberine inhibited adipogenesis in murine
      derived 3T3-L1 preadipocytes and human white preadipocytes. In this study, the
      effects of berberine on the adipogenesis of high-fat diet-induced obesity (FD) or
      normal diet (ND) mice and possible transcriptional impact are investigated. The
      results demonstrated that in FD mice, berberine reduced mouse weight gain and
      food intake and serum glucose, triglyceride, and total cholesterol levels
      accompanied with a down-regulation of PPARgamma expression and an up-regulation
      of GATA-3 expression. Berberine had no adverse effects on ND mice. These
      encouraging findings suggest that berberine has excellent pharmacological
      potential to prevent obesity.

PMID- 19861154
TI  - Enhancement of muscle cell glucose uptake by medicinal plant species of Canada's
      native populations is mediated by a common, metformin-like mechanism.
AB  - AIM: The purpose of the present study was to elucidate the mechanisms of action
      mediating enhancement of basal glucose uptake in skeletal muscle cells by seven
      medicinal plant products recently identified from the pharmacopeia of native
      Canadian populations (Spoor et al., 2006). METHODS: Activity of the major
      signaling pathways that regulate glucose uptake was assessed by western
      immunoblot in C2C12 muscle cells treated with extracts from these plant species.
      Effects of extracts on mitochondrial function were assessed by respirometry in
      isolated rat liver mitochondria. Metabolic stress induced by extracts was
      assessed by measuring ATP concentration and rate of cell medium acidification in
      C2C12 myotubes and H4IIE hepatocytes. Extracts were applied at a dose of 15-100
      microg/ml. RESULTS: The effect of all seven products was achieved through a
      common mechanism mediated not by the insulin signaling pathway but rather by the
      AMP-activated protein kinase (AMPK) pathway in response to the disruption of
      mitochondrial function and ensuing metabolic stress. Disruption of mitochondrial
      function occurred in the form of uncoupling of oxidative phosphorylation and/or
      inhibition of ATPsynthase. Activity of the AMPK pathway, in some instances
      comparable to that stimulated by 4mM of the AMP-mimetic AICAR, was in several
      cases sustained for at least 18h post-treatment. Duration of metabolic stress,
      however, was in most cases in the order of 1h. CONCLUSIONS: The mechanism common
      to the seven products studied here is analogous to that of the antidiabetic drug
      Metformin. Of interest is the observation that metabolic stress need not be
      sustained in order to induce important adaptive responses. The results support
      the use of these products as culturally adapted treatments for insulin resistance
      and hyperglycemia in susceptible aboriginal populations where adherence to modern
      diabetes pharmaceuticals is an issue. The mechanism reported here may be
      widespread and mediate the antidiabetic activity of traditional remedies from
      various other cultures.

PMID- 19861155
TI  - Antinociceptive activity of fractions from Couroupita guianensis Aubl. leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Couroupitaguianensis Aubl. (Lecythidaceae) is
      popularly known in Brazil as "abrico-de-macaco". Infusions or teas obtained from
      its leaves, flowers, and barks are used in South America for the treatment of
      several disorders such as pain and inflammatory processes. AIM OF THE STUDY:
      Evaluate antinociceptive effects of crude ethanol extract (CEE) and its fractions
      in three analgesic models (acetic acid-induced contortions, tail flick, and hot
      plate) and study the possible mechanism of their action. MATERIALS AND METHODS:
      CEE, hexane, dichloromethane, ethyl acetate, and butanol fractions (10, 30, and
      100mg/kg, p.o.) and the reference drug morphine (5mg/kg, s.c.) were evaluated. To
      elucidate the mechanism of action from the fractions, animals were pre-treated
      (30 min) with atropine (muscarinic receptor antagonist, 1mg/kg, s.c.),
      mecamylamine (nicotinic receptor antagonist, 2mg/kg, s.c.), naloxone (opioid
      receptor antagonist, 1mg/kg, s.c.) or L-nitro arginine methyl ester (L-NAME,
      nitric oxide synthase inhibitor, 3mg/kg, s.c.). RESULTS: CEE and fractions
      significantly inhibited the number of contortions induced by acetic acid. All
      fractions showed antinociceptive activity in the tail flick model, being the
      hexane and ethyl acetate the most potent and long acting fractions. In the hot
      plate method the highest effect observed was at the dose of 100mg/kg from all
      fractions. Administration of naloxone inhibited the antinociceptive effect of
      fractions. Pre-treatment of mice with atropine reduced the antinociceptive
      activity of CEE and its fractions, the exception being the dichloromethane
      fraction. Mecamylamine did not inhibited the effect of dichloromethane fraction.
      L-NAME reduced the anti-hyperalgesic effect of all fractions, but the most
      prominent effect was observed in the antinociceptive activity caused by CEE and
      butanol fraction. CONCLUSIONS: Results obtained demonstrated that Couroupita
      guianensis CEE and its fractions have antinociceptive activity that is mediated,
      at least in part, by opioid and cholinergic systems and nitric oxide pathway.

PMID- 19861156
TI  - Attenuation of the influenza virus sickness behavior in mice deficient in Toll
      like receptor 3.
AB  - Certain sickness behaviors occur consistently in influenza-infected humans and
      mice. These include body temperature changes, somnolence, and anorexia. Several
      cytokines serve as mediators of the influenza acute phase response (APR),
      including these sickness behaviors, and one likely inducer of these cytokines is
      dsRNA produced during viral replication. TLR3 is known to be one of the host
      cellular components capable of recognizing dsRNA and activating cytokine
      synthesis. To determine the role of TLR3-detected viral dsRNA in the causation of
      viral symptoms, TLR3-deficient mice (TLR3 knockouts, or KOs) were infected with a
      marginally-lethal dose of mouse-adapted X-31 influenza virus. TLR3 KOs and their
      wild-type (WT) controls were monitored for baseline body temperature, locomotor
      activity, and sleep profiles prior to infection. Both mouse strains were then
      infected and monitored for changes in these sickness behaviors plus body weight
      changes and mortality for up to 14days post-infection. Consistent with the
      observations that influenza pathology is reduced in TLR3 KOs, we showed that
      hypothermia after post-infection day 5 and the total loss of body weight were
      attenuated in the TLR3 KOs. Sleep changes characteristic of this infection model
      [particularly increased non-rapid-eye-movement sleep (NREMS)] were also
      attenuated in TLR3 KOs and returned to baseline values more rapidly. Locomotor
      activity suppression was similar in both strains. Therefore virus-associated
      dsRNA detected by TLR3 appears to play a substantial role in mediating several
      aspects of the influenza syndrome in mice.

PMID- 19861157
TI  - Systemic inflammation sensitizes the neonatal brain to excitotoxicity through a
      pro-/anti-inflammatory imbalance: key role of TNFalpha pathway and protection by
      etanercept.
AB  - Systemic inflammation sensitizes the perinatal brain to an ischemic/excitotoxic
      insult but the mechanisms are poorly understood. We hypothesized that the
      mechanisms involve an imbalance between pro- and anti-inflammatory factors. A
      well characterized mouse model where a systemic injection of IL-1beta during the
      first five postnatal days (inflammatory insult) is combined with an intracerebral
      injection of the glutamatergic analogue ibotenate (excitotoxic insult) at
      postnatal day 5 was used. Following the inflammatory insult alone, there was a
      transient induction of IL-1beta and TNFalpha, compared with controls measured by
      quantitative PCR, ELISA, and Western blot. Following the combined inflammatory
      and excitotoxic insult, there was an induction of IL-1beta, TNFalpha, and IL-6
      but not of IL-10 and TNFR1, indicating an altered pro-/anti-inflammatory balance
      after IL-1beta sensitized lesion. We then tested the hypothesis that the TNFalpha
      pathway plays a key role in the sensitization and insult using TNFalpha blockade
      (etanercept) and TNFalpha(-/-) mice. Etanercept given before the insult did not
      affect brain damage, but genetic deletion of TNFalpha or TNFalpha blockade by
      etanercept given after the combined inflammatory and excitotoxic insult reduced
      brain damage by 50%. We suggest this protective effect was centrally mediated,
      since systemic TNFalpha administration in the presence of an intact blood-brain
      barrier did not aggravate the damage and etanercept almost abolished cerebral
      TNFalpha production. In summary, sensitization was, at least partly, mediated by
      an imbalance between pro- and anti-inflammatory cytokines. Cerebral TNFalpha
      played a key role in mediating brain damage after the combined inflammatory and
      excitatory insult.

PMID- 19861158
TI  - Insulin/IGF-1 paradox of aging: regulation via AKT/IKK/NF-kappaB signaling.
AB  - GH/insulin/IGF-1 signaling is a vital pathway e.g. in the regulation of protein
      synthesis and glucose metabolism. However, mouse dwarf strains which exhibit
      reduced GH secretion and subsequently a decline in IGF-1 signaling can live
      longer than their wild type counterparts. There is striking evidence indicating
      that the IGF-1/PI-3K/AKT signaling enhances growth of animals during development
      but later in life can potentiate the aging process. This conserved pleiotropy has
      been called the insulin/IGF-1 paradox. In Caenorhabditiselegans, the decline in
      this pathway activates the DAF-16 gene, an ortholog of mammalian FoxO genes,
      which regulate stress resistance and longevity. The mammalian PI-3K/AKT pathway
      also activates the NF-kappaB signaling that inhibits apoptosis and triggers
      inflammatory responses. Many longevity genes, e.g. FoxOs and SIRT1, are
      inhibitors of NF-kappaB signaling. We will discuss the evidence that insulin/IGF
      1 signaling can enhance the NF-kappaB signaling and subsequently potentiate the
      aging process and aggravate age-related degenerative diseases.

PMID- 19861159
TI  - Oxygen-sensing under the influence of nitric oxide.
AB  - The transcription factor complex Hypoxia inducible factor 1 (HIF-1) controls the
      expression of most genes involved in adaptation to hypoxic conditions. Oxygen
      dependency is maintained by prolyl- and asparagyl-4-hydroxylases (PHDs/FIH-1)
      belonging to the superfamily of iron(II) and 2-oxoglutarate dependent
      dioxygenases. Hydroxylation of the HIF-1alpha subunit by PHDs and FIH-1 leads to
      its degradation and inactivation. By hydroxylating HIF-1alpha in an oxygen
      dependent manner PHDs and FIH-1 function as oxygen-sensing enzymes of HIF
      signalling. Besides molecular oxygen nitric oxide (NO), a mediator of the
      inflammatory response, can regulate HIF-1alpha accumulation, HIF-1 activity and
      HIF-1 dependent target gene expression. Recent studies addressing regulation of
      HIF-1 by NO revealed a complex and paradoxical picture. Acute exposure of cells
      to high doses of NO increased HIF-1alpha levels irrespective of the residing
      oxygen concentration whereas prolonged exposure to NO or low doses of this
      radical reduced HIF-1alpha accumulation even under hypoxic conditions. Several
      mechanisms were found to contribute to this paradoxical role of NO in regulating
      HIF-1. More recent studies support the view that NO regulates HIF-1 by modulating
      the activity of the oxygen-sensor enzymes PHDs and FIH-1. NO dependent HIF-1alpha
      accumulation under normoxia was due to direct inhibition of PHDs and FIH-1 most
      likely by competitive binding of NO to the ferrous iron in the catalytically
      active center of the enzymes. In contrast, reduced HIF-1alpha accumulation by NO
      under hypoxia was mainly due to enhanced HIF-1alpha degradation by induction of
      PHD activity. Three major mechanisms are discussed to be involved in enhancing
      the PHD activity despite the lack of oxygen: (1) NO mediated induction of a HIF-1
      dependent feedback loop leading to newly expressed PHD2 and enhanced nuclear
      localization, (2) O2-redistribution towards PHDs after inhibition of
      mitochondrial respiration by NO, (3) reactivation of PHD activity by a NO
      mediated increase of iron and 2-oxoglutarate and/or involvement of reactive
      oxygen and/or nitrogen species.

PMID- 19861160
TI  - Modulation of immune cell signalling by the leukocyte common tyrosine
      phosphatase, CD45.
AB  - CD45 is a leukocyte specific transmembrane glycoprotein and a receptor-like
      protein tyrosine phosphatase (PTP). CD45 can be expressed as several
      alternatively spliced isoforms that differ in the extracellular domain. The
      isoforms are regulated in a cell type and activation state-dependent manner, yet
      their function has remained elusive. The Src family kinase members Lck and Lyn
      are key substrates for CD45 in T and B lymphocytes, respectively. CD45 lowers the
      threshold of antigen receptor signalling, which impacts T and B cell activation
      and development. CD45 also regulates antigen triggered Fc receptor signalling in
      mast cells and Toll-like receptor (TLR) signalling in dendritic cells, thus
      broadening the role of CD45 to other recognition receptors involved in adaptive
      and innate immunity. In addition, CD45 can affect immune cell adhesion and
      migration and can modulate cytokine production and signalling. Here we review
      what is known about the substrate specificity and regulation of CD45 and
      summarise its effect on immune cell signalling pathways, from its established
      role in T and B antigen receptor signalling to its emerging role regulating
      innate immune cell recognition and cytokine production.

PMID- 19861161
TI  - c-Cbl acts as a mediator of Src-induced activation of the PI3K-Akt signal
      transduction pathway during TRAIL treatment.
AB  - We have previously observed that TRAIL (tumor necrosis factor-related apoptosis
      inducing ligand) induces acquired TRAIL resistance by increasing Akt
      phosphorylation and Bcl-xL expression. In this study, we report that Src, c-Cbl,
      and PI3K are involved in the phosphorylation of Akt during TRAIL treatment. Data
      from immunoprecipitation and immunoblotting assay reveal that Src interacts with
      c-Cbl and PI3K. Data from immune complex kinase assay demonstrate that Src can
      directly phosphorylate c-Cbl and PI3K p85 subunit protein. Data from gene
      knockdown experiments with an RNA interference (RNAi) technique show that c-Cbl
      is involved in the interaction between Src and PI3K p85 during TRAIL treatment,
      playing an important role in TRAIL-induced Akt phosphorylation. Taken together, c
      Cbl may act as a mediator to regulate the Src-PI3K-Akt signal transduction
      pathway during TRAIL treatment.

PMID- 19861162
TI  - Hedgehog pathway activity is required for the lethality and intestinal phenotypes
      of mice with hyperactive Wnt signaling.
AB  - Several lines of evidence point to the central role of WNT signaling in the
      initiation of intestinal tumorigenesis, most often due to loss of APC, a negative
      regulator of the WNT-betaCATENIN/TCF pathway. Modeling human colon cancers in
      mice through loss of Apc has shown that inappropriate activation of Wnt signaling
      is sufficient to induce adenoma formation. More recent analyses have also
      demonstrated a key role for HEDGEHOG-GLI (HH-GLI) signaling in human colon
      cancers. However, how the WNT and HH pathways interact during intestinal
      development, homeostasis and cancer is not clear. Marker analyses suggest
      predominant paracrine signaling from rare Shh producing cells in the crypt's
      bottom to adjacent Gli1(+) mesenchymal cells in normal adult mice. Using
      conditional KO models, we show that inhibition of the function of the critical Hh
      mediator Smoothened (Smo) rescues the lethality and intestinal phenotypes of loss
      of Apc. The results uncover an essential role of the Hh pathway in tumors induced
      by hyperactive Wnt signaling, suggest the action of the Hh pathway in parallel or
      downstream of Wnt signaling, and validate this model for its use in preclinical
      work testing Hh pathway antagonists.

PMID- 19861163
TI  - Inulin solid dispersion technology to improve the absorption of the BCS Class IV
      drug TMC240.
AB  - TMC240 is a very poorly soluble and poorly permeating HIV protease inhibitor. In
      order to enhance its oral bioavailability, a fast dissolving inulin-based solid
      dispersion tablet was developed. During the dissolution test in water (0.5% or
      1.0% SLS), this tablet released at least 80% of TMC240 within 30min, while a
      tablet with the same composition, but manufactured as physical mixture, released
      only 6% after 2h. In a subsequent single-dose study in dogs (200mg of TMC240),
      plasma concentrations of TMC240 remained below the lower limit of quantification
      (<1.00ng/mL) in all animals (n=3 per tested formulation), except in one dog
      receiving the inulin solid dispersion tablet (C(max)=1.8ng/mL, AUC(0-7
      h)=3.0ngh/mL). In the latter treatment group, ritonavir co-administration
      (10mg/kg b.i.d.) increased TMC240 exposure more than 30-fold (mean AUC(0-7
      h)=108ngh/mL; F(rel)=3588%). Exposure was also 16-fold higher than after TMC240
      administration as PEG400 suspension in the presence of ritonavir (AUC(0-7
      h)=6.7ngh/mL). The current data demonstrate that a solid dispersion of TMC240 in
      an inulin matrix allows considerable improvement in the release of poorly water
      soluble TMC240, both in vitro in the presence of a surfactant and in vivo upon
      oral administration.

PMID- 19861164
TI  - BmCAP, a silkmoth gene encoding multiple protein isoforms characterized by SoHo
      and SH3 domains: expression analysis during ovarian follicular development.
AB  - CAP/ArgBP2/vinexin family proteins, adaptor proteins characterized by three SH3
      domains at their C-termini and a SoHo domain towards their N-termini, are known
      to regulate cell adhesion, cytoskeletal organization, and growth factor
      signaling. Here we present the isolation and ovarian expression of the BmCAP gene
      which encodes CAP/ArgBP2/vinexin family proteins in the silkmoth, Bombyx mori.
      Screening for full-length cDNA clones identified three mRNA isoforms, BmCAP-A1,
      BmCAP-A2 and BmCAP-B, which show expression throughout ovarian follicular
      development. Using an antibody raised against a unique region between the SoHo
      and SH3 domains, BmCAP-A protein isoforms were identified that show specific
      expression in different compartments of the ovarian follicles. Immunofluorescence
      staining of the cells of the follicular epithelium establishes a dynamic pattern
      of BmCAP-A protein localization during choriogenesis. During early choriogenesis,
      BmCAP-A has a diffuse localization in the cytoplasm but could also be found
      concentrated at the apical and basal sides at the cell-cell junctions. During
      late choriogenesis, the diffuse cytoplasmic staining of BmCAP-A disappears while
      the staining pattern at the apical side resembles a blueprint for the eggshell
      surface structure. We suggest that BmCAP-A isoforms have important functions
      during ovarian development, which involve not only the traditional roles in actin
      organization or cell-cell adhesion but also the regulation of secretion of
      chorion proteins and the sculpting of the chorion surface.

PMID- 19861165
TI  - Cytogenetic contributions for the study of the Amazonian Engystomops (Anura;
      Leiuperidae) assessed in the light of phylogenetic relationships.
AB  - Genetic divergence and speciation mechanisms of the Amazonian Engystomops frog
      have been inferred mainly from mtDNA sequences, microsatellite and male
      advertisement call. Although many aspects of this divergence remain unclear,
      cytogenetic analyses of Amazonian Engystomops populations are described and are
      compared to the relationships inferred from mitochondrial and nuclear DNA
      sequence data. High cytogenetic variation distinguished karyotypic patterns among
      the populations, even between populations which had no prezygotic isolation
      previously inferred from mating call analysis. Interestingly, the Puyo and Acre
      populations, which are in different clades, showed heteromorphic sex chromosomes
      (XX/XY), not identified in the other Ecuatorian populations analyzed. The
      analysis of a specimen collected in a site near Yasuni (Ecuador) which was
      cytogenetically related to the specimens from Puyo (Ecuador), was also
      phylogenetically closely related these specimens. In the rhodopsin nucleotide
      sequences, six polymorphic sites were identified and various specimens were
      heterozygous for them. All the data presented herein, in conjunction with those
      previously reported, corroborate the hypothesis that Engystomops petersi is a
      complex of distinct species. It also indicates that karyotypic evolution patterns
      may have played a substantial role in the Engystomops speciation and the
      occurrence of sporadic mating events between divergent evolutive lineages is
      discussed.

PMID- 19861166
TI  - A comparison of three rapid and accurate bioluminescent antibiotic susceptibility
      tests.
AB  - INTRODUCTION: Rapid determination of microorganisms' antibiotic susceptibility
      remains a great challenge for the clinical diagnosis of infectious diseases. In
      this study, we compare three rapid bioluminescent antibiotic susceptibility tests
      with the conventional normalised microdilution method. METHODS: The
      susceptibility of two bacterial and two fungal strains to a 6h incubation with
      one of eight standard antibiotics was investigated by the ATP, AK and QNO
      bioluminescent methods. RESULTS: Three rapid and accurate antibiotic
      susceptibility testing were investigated performing ATP, AK and QNO
      bioluminescent assays. All the results were in accordance with those obtained
      using a standard microdilution assay. All these methods were sensitive and faster
      than the previously well-known ones. DISCUSSION: The development of
      bioluminescent determination methods could lead to accurate and useful antibiotic
      susceptibility testing.

PMID- 19861167
TI  - Metabolic flux analysis and pharmaceutical production.
AB  - Rational engineering of biological systems is an inherently complex process due
      to their evolved nature. Metabolic engineering emerged and developed over the
      past 20 years as a field in which methodologies for the rational engineering of
      biological systems is now being applied to specific industrial, medical, or
      scientific problems. Of considerable interest is the determination of metabolic
      fluxes within the cell itself, called metabolic flux analysis. This special issue
      and this review have a particular interest in the application of metabolic flux
      analysis for improving the pharmaceutical production process (for both small and
      large molecules). Though metabolic flux analysis has been somewhat limited in
      application towards pharmaceutical production, the overall goal is to: (1) have a
      better understanding of the organism and/or process in question, and (2) provide
      a rational basis to further engineer (on both metabolic and process scales)
      improved pharmaceutical production in these organisms. The focus of this review
      article is to present how experimental and computational methods of metabolic
      flux analysis have matured, mirroring the maturation of the metabolic engineering
      field itself, while highlighting some of the successful applications towards both
      small- and large-molecule pharmaceuticals.

PMID- 19861168
TI  - Acidic residues in the purine binding site govern the 6-oxopurine specificity of
      the Leishmania donovani xanthine phosphoribosyltransferase.
AB  - Leishmania possess distinct xanthine phosphoribosyltransferase and hypoxanthine
      guanine phosphoribosyltransferase enzymes that mediate purine salvage, an
      obligatory nutritional function for these pathogenic parasites. The xanthine
      phosphoribosyltransferase preferentially uses xanthine as a substrate, while the
      hypoxanthine-guanine phosphoribosyltransferase phosphoribosylates only
      hypoxanthine and guanine. These related phosphoribosyltransferases were used as
      model system to investigate the molecular determinants regulating the 6-oxopurine
      specificity of these enzymes. Analysis of the purine binding domains showed two
      conserved acidic amino acids; glutamate residues in the xanthine
      phosphoribosyltransferase (E198 and E215) and aspartate residues in the
      hypoxanthine-guanine phosphoribosyltransferase (D168 and D185). Genetic and
      biochemical analysis established that the single E198D and E215D mutations
      increased the turnover rates of the xanthine phosphoribosyltransferase without
      altering purine nucleobase specificity. However, the E215Q and E198,215D
      mutations converted the Leishmania xanthine phosphoribosyltransferase into a
      broad-specificity enzyme capable of utilizing guanine, hypoxanthine, and xanthine
      as substrates. Similarly, the D168,185E double mutation transformed the
      Leishmania hypoxanthine-guanine phosphoribosyltransferase into a mutant enzyme
      capable phosphoribosylating only xanthine, albeit with a much lower catalytic
      efficiency. These studies established that these conserved acidic residues play
      an important role in governing the nucleobase selectivity of the Leishmania 6
      oxopurine phosphoribosyltransferases.

PMID- 19861169
TI  - Modulation of interleukin signalling and gene expression in cardiac myocytes by
      endothelin-1.
AB  - The related inflammatory cytokines, interleukin- (IL-) 1beta and IL-33, are both
      implicated in the response of the heart to injury. They also activate mitogen
      activated protein kinases (MAPKs) in cardiac myocytes. The hypertrophic Gq
      protein-coupled receptor agonist endothelin-1 is a potentially cardioprotective
      peptide and may modulate the inflammatory response. Endothelin-1 also stimulates
      (MAPKs) in cardiac myocytes and promotes rapid changes in expression of mRNAs
      encoding intercellular and intracellular signalling components including
      receptors for IL-33 (ST2) and phosphoprotein phosphatases. Prior exposure to
      endothelin-1 may specifically modulate the response to IL-33 and, more globally,
      influence MAPK activation by different stimuli. Neonatal rat ventricular myocytes
      were exposed to IL-1beta or IL-33 with or without pre-exposure to endothelin-1
      (5h) and MAPK activation assessed. IL-33 activated ERK1/2, JNKs and p38-MAPK, but
      to a lesser degree than IL-1beta. Endothelin-1 increased expression of soluble IL
      33 receptors (sST2 receptors) which may prevent binding of IL-33 to the cell
      surface receptors. However, pretreatment with endothelin-1 only inhibited
      activation of p38-MAPK by IL-33 with no significant influence on ERK1/2 and a
      small increase in activation of JNKs. Inhibition of p38-MAPK signalling following
      pretreatment with endothelin-1 was also detected with IL-1beta, H(2)O(2) or
      tumour necrosis factor alpha (TNFalpha) indicating an effect intrinsic to the
      signalling pathway. Endothelin-1 pretreatment suppressed the increase in
      expression of IL-6 mRNA induced by IL-1beta and decreased the duration of
      expression of TNFalpha mRNA. Coupled with the general decrease in p38-MAPK
      signalling, we conclude that endothelin-1 attenuates the cardiac myocyte
      inflammatory response, potentially to confer cardioprotection.

PMID- 19861170
TI  - Analysis of phosphorylated proteins and inhibition of kinase activity during
      Giardia intestinalis excystation.
AB  - The parasite Giardia intestinalis undergoes a differentiation process that allows
      it to infect its mammal host. That process is excystation. We examined the
      importance of protein phosphorylation during the passage from cyst to
      trophozoite. Cysts obtained from patients with giardiasis were excysted in vitro
      and the soluble cytoplasmic proteins were analyzed during the three phases of the
      process, using a specific staining for phosphoproteins. We found two
      phosphorylated proteins and identified them with MALDI-TOF as 14-3-3 and Hsp70.
      Modifications were detected in both proteins, which could indicate a role in
      differentiation of the parasite. In addition, the inhibition of serine-threonine
      kinases during excystation specifically affected the cytokinesis of the
      excyzoite, thus inhibiting the completion of trophozoite formation.

PMID- 19861171
TI  - Changes in the auditory neuropil after deafferentation in adult grasshoppers
      (Schistocerca gregaria).
AB  - Nervous systems are capable of structural adjustments. Such plastic changes also
      occur in the auditory system of the locust Schistocerca gregaria in which a
      deafferentation leads to compensatory mechanisms, such as collateral sprouting of
      interneurons. In this study we further investigated lesion related changes in the
      major auditory neuropil, the median ventral association center (mVAC) of the
      metathoracic ganglion. The auditory sensory organ of adult locusts was
      unilaterally extirpated and the mVAC was histologically and immunocytochemically
      analyzed until 20 days postoperative. Measurements of the neuropil area in
      transverse sections showed a decrease in size. The putative transmitter of the
      afferents, acetylcholine, was investigated by acetylcholinesterase
      histochemistry. Comparisons of staining intensities in the intact and
      deafferentated mVAC indicated that the amount of acetylcholinesterase in the
      deafferentated mVAC decreased shortly after the operation. Both, the decreases in
      size of the mVAC as well as that in acetylcholinesterase histochemistry were only
      less than 10% compared to the controls. The immunoreactivity against the
      neurotransmitters gamma-amino butyric acid and serotonin was not influenced by
      the deafferentation.

PMID- 19861172
TI  - Responses to cadmium intoxication in the liver of the wall lizard Podarcis
      sicula.
AB  - This study examined the cytological and molecular effects of cadmium, a toxic
      heavy metal, in the liver of the Italian wall lizard Podarcis sicula. Cadmium was
      administered in single dose, by diet, to induce a concentration comparable with
      that measured in animals living in contaminated sites. For comparison, cadmium
      was also administered in multiple doses by food (chronic) or in a single dose
      intraperitoneally (i.p.); the effects were followed at regular time intervals up
      to 30 days post treatments. Atomic absorption spectrometry analysis demonstrated
      cadmium ion uptake and accumulation in the parenchyma with an estimated half-life
      of approximately 8 days. Cytological analyses revealed that the metal induced
      oedema, activated metallothionein expression in Kupffer cells and extracellular
      matrix production in fat storing cells. It also caused swelling and alteration in
      lipid and sugar metabolism in hepatocytes. In conclusion, in the wall lizard
      cadmium is toxic to the liver even at very low concentrations, the response is
      not strictly dose and time dependent and almost no recovery occurs in short (30
      days) time periods.

PMID- 19861173
TI  - Thioredoxin and HSP90 alpha modulate ASK1-JNK1/2 signaling in stressed
      hepatocytes of Mugil cephalus.
AB  - Induction of antioxidant proteins like thioredoxin (Trx) and heat shock protein
      90 alpha (HSP90 alpha) is a crucial step in the cellular response to oxidative
      stress. Here, we report the impact of environmental stress on Trx and HSP90 alpha
      expressions in freshly isolated hepatocytes of Mugil cephalus living in either a
      contaminated (Test; Ennore) or uncontaminated (Control; Kovalam) estuary.
      Modulation in the activities of signal transduction molecules like apoptosis
      signal-regulating kinase 1 (ASK1) and c-Jun NH(2)-terminal kinase 1/2 (JNK1/2)
      were also investigated to understand their functional role under natural stressed
      condition. The expression pattern of the proteins was determined by
      immunoblotting and the relationship between the proteins was identified by
      regression analysis. Test fish hepatocytes demonstrated significant upregulation
      (P<0.05) in the levels of Trx and HSP90 alpha and insignificant inductions in the
      expression pattern of ASK1 and JNK1/2 than control fish hepatocytes. These
      findings provide direct evidence that Trx and HSP90 alpha induction in fish
      hepatocytes under stress may aid cell survival by negatively regulating ASK1
      expression and thereby functionally antagonizing the apoptotic role of JNK1/2 in
      natural aquatic systems.

PMID- 19861176
TI  - Expression of the AMACO (VWA2 protein) ortholog in zebrafish.
AB  - AMACO is a basement membrane associated protein that belongs to the VWA domain
      containing protein superfamily. In addition to three VWA domains it contains two
      EGF-like domains, a cysteine-rich domain and a unique domain. Mouse AMACO has
      been partially characterized, but its function remains unknown. The zebrafish
      genome contains a single AMACO ortholog gene on chromosome 12. The domain
      structure is completely conserved between zebrafish and mouse and the first EGF
      like domain, carrying a rare O-glucosylation and O-fucosylation consensus
      sequence, has the highest identity at the protein level. RT-PCR shows strongest
      AMACO expression during development, starting at the 5 somite stage. An antibody
      specific for zebrafish AMACO detected expression mainly in myosepta but also in
      skin, pronephros, pituitary gland, otic capsule and gills. In situ hybridization
      revealed that the muscle precursor cells of the somites express the protein that
      is laid down in the myosepta.

PMID- 19861177
TI  - Biomineralized strontium-substituted apatite/titanium dioxide coating on titanium
      surfaces.
AB  - Bone mineral is a multi-substituted calcium phosphate. One of these ion
      substitutions, strontium, has been proven to increase bone strength and decrease
      bone resorption. Biomimetics is a potential way to prepare surfaces that provide
      a favorable bone tissue response, thus enhancing the fixation between bone and
      implants. Here we prepared double-layered strontium-substituted apatite and
      titanium dioxide coatings on titanium substrates via mimicking bone
      mineralization. Morphology, crystallinity, surface chemistry and composition of
      Sr-substituted coatings formed via biomimetic coating deposition on crystalline
      titanium oxide substrates were studied as functions of soaking temperature and
      time in phosphate buffer solutions with different Sr ion concentration. The
      morphology of the biomimetic apatite changed from plate-like for the pure HA to
      sphere-like for the Sr ion substituted. Surface analysis results showed that 10
      33% of Ca ions in the apatite have been substituted by Sr ions, and that the Sr
      ions were chemically bonded with apatite and successfully incorporated into the
      structure of apatite.

PMID- 19861178
TI  - Effect of chitosan scaffold microstructure on mesenchymal stem cell
      chondrogenesis.
AB  - Although numerous biomaterials have been investigated as scaffolds for cartilage
      tissue engineering, the effect of their microstructure on final construct
      characteristics remains unclear. The biocompatibility of chitosan and its
      similarity with glycosaminoglycans make it attractive as a scaffold for cartilage
      engineering. Our objective was to evaluate the effect of chitosan scaffold
      structure on mesenchymal stem cell proliferation and chondrogenesis. Chitosan
      fibrous scaffolds and chitosan sponges were seeded with mesenchymal stem cells in
      a chondrogenic medium. Constructs were analyzed 72 h after seeding via scanning
      electron microscopy (SEM), weight measurements and DNA quantification. Constructs
      were cultured for 10 or 21 days prior to confocal microscopy, SEM, histology,
      quantitative analysis (weight, DNA and glycosaminoglycan (GAG)), and quantitative
      real-time polymerase chain reaction. Mesenchymal stem cells maintained a
      viability above 90% on all chitosan scaffolds. The cell numbers in the constructs
      were similar at 72 h, 10 days and 21 days. However, matrix production was
      improved in chitosan fibrous constructs based on the GAG quantification and
      collagen II mRNA expression. Chondrogenesis on chitosan scaffolds is superior on
      microfibers compared to macroporous sponges.

PMID- 19861179
TI  - Cobalt, chromium and nickel affect hydroxyapatite crystal growth in vitro.
AB  - Metals are widely used in orthopaedics and recent studies have reported that
      patients with metal implants have a significant increase of metal levels in serum
      and synovial fluid. Femoral neck fracture occurred in some patients with metal-on
      metal implants for unknown reasons. Recently, bone quality has emerged as an
      important factor of bone strength and few studies have investigated the effects
      of metal ions on hydroxyapatite properties. In the present study, we investigated
      the effects of Co(2+), Cr(3+) and Ni(2+) on hydroxyapatite (HA) growth in vitro,
      using carboxymethylated poly(2-hydroxyethyl methacrylate) (pHEMA) as a
      biomaterial for calcification. We have demonstrated that metal ions reduced the
      quantity of mineral formed at the surface of the polymer and decreased the ratio
      Ca/P by 1.12-, 1.05- and 1.08-fold for Cr(2+), Cr(3+) and Ni(2+) respectively.
      Furthermore, the size of calcospherites was significantly increased in the metal
      doped HA compared to the controls, indicating a possible effect of metal ions on
      the crystal lattice. Indeed, the presence of metal ions increased the crystal
      size as well as the crystallinity of HA and reduce the lattice parameter c of the
      HA framework. The information obtained from this work suggests that the quality
      of the mineral around metallic implants could be altered. However, further
      investigation should be conducted to further elucidate the effects of metal
      incorporation on bone mineral and the functional consequences.

PMID- 19861180
TI  - Adhesion, migration and mechanics of human adipose-tissue-derived stem cells on
      silk fibroin-chitosan matrix.
AB  - Silk fibroin-chitosan (SFCS) scaffold is a naturally derived biocompatible matrix
      with potential reconstructive surgical applications. In this study, human adipose
      derived mesenchymal stem cells (ASCs) were seeded on SFCS scaffolds and cell
      attachment was characterized by fluorescence, confocal, time-lapse, atomic force,
      and scanning electron microscopy (SEM) studies. Adhesion of ASCs on SFCS was 39.4
      + or - 4.8% at 15 min, increasing to 92.8+/-1.5% at 120 min. ASC adhered at
      regions of architectural complexity and infiltrate into three-dimensional
      scaffold. Time-lapse confocal studies indicated a mean ASC speed on SFCS of
      18.47+/-2.7 microm h(-1) and a mean persistence time of 41.4 + or - 9.3 min over
      a 2.75 h study period. Cytokinetic and SEM studies demonstrated ASC-ASC
      interaction via microvillus extensions. The apparent elastic modulus was
      significantly higher (p<0.0001) for ASCs seeded on SFCS (69.0 + or - 9.0 kPa)
      than on glass (6.1 + or - 0.4 kPa). Also, cytoskeleton F-actin fiber density was
      higher (p<0.05) for ASC seeded on SFCS (0.42 + or - 0.02 fibers microm(-1)) than
      on glass-seeded controls (0.24 + or - 0.03 fibers microm(-1)). Hence, SFCS
      scaffold facilitates mesenchymal stem cell attachment, migration, three
      dimensional infiltration, and cell-cell interaction. This study showed the
      potential use of SFCS as a local carrier for autologous stem cells for
      reconstructive surgery application.

PMID- 19861181
TI  - Incorporation of biodegradable electrospun fibers into calcium phosphate cement
      for bone regeneration.
AB  - Inherent brittleness and slow degradation are the major drawbacks for the use of
      calcium phosphate cements (CPCs). To address these issues, biodegradable
      ultrafine fibers were incorporated into the CPC in this study. Four types of
      fibers made of poly(epsilon-caprolactone) (PCL) (PCL12: 1.1 microm, PCL15: 1.4
      microm, PCL18: 1.9 microm) and poly(l-lactic acid) (PLLA4: 1.4 microm) were
      prepared by electrospinning using a special water pool technique, then mixed with
      the CPC at fiber weight fractions of 1%, 3%, 5% and 7%. After incubation of the
      composites in simulated body fluid for 7 days, they were characterized by a
      gravimetric measurement for porosity evaluation, a three-point bending test for
      mechanical properties, microcomputer topography and scanning electron microscopy
      for morphological observation. The results indicated that the incorporation of
      ultrafine fibers increases the fracture resistance and porosity of CPCs. The
      toughness of the composites increased with the fiber fraction but was not
      affected by the fiber diameter. It was found that the incorporated fibers formed
      a channel-like porous structure in the CPCs. After degradation of the fibers, the
      created space and high porosity of the composite cement provides inter-connective
      channels for bone tissue in growth and facilitates cement resorption. Therefore,
      we concluded that this electrospun fiber-CPC composite may be beneficial to be
      used as bone fillers.

PMID- 19861182
TI  - Effects of micrometric titanium particles on osteoblast attachment and
      cytoskeleton architecture.
AB  - Titanium (Ti) and its alloys are widely used in biomedical devices as bone tissue
      replacements due to their advantageous bulk mechanical properties and
      biocompatibility. It is known that particles released from Ti-based implants
      impair essential functions of osteoblasts, which for survival require attachment
      to specific extracellular matrix proteins at the bone surface. This study
      investigates whether Ti particles of micrometric sizes affect the osteoblast
      attachment machinery. Exposure of human osteoblastic Saos-2 cells to Ti particles
      impaired their adhesion strength, migration and proliferation. Attenuation of
      these functions was associated with reduced cell spreading, cell membrane
      disruptions and loss of cell shape. Cell exposure to Ti particles led to changes
      in cytoskeletal structures, including reduced ventral stress fibers combined with
      a disorderly arrangement of beta-tubulin and acetylated alpha-tubulin fibers.
      Cytoskeleton disassembly was associated with a reduction in overall cell adhesion
      area, characterized by fewer centrally localized focal adhesions and shorter
      focal contacts at the periphery. Paxillin adaptor protein redistributed to
      peripheral corner regions, colocalizing with poorly organized actin fibers at
      attachment sites. Total focal adhesion kinase (FAK) protein amounts, as well as
      its degree of phosphorylation on the active form p-FAK (Tyr-397), decreased,
      which was accompanied by a lesser extent of co-localization with paxillin in
      focal contacts. On the other hand, p-FAK (Tyr-407), an inhibitory form of FAK,
      accumulated in the focal contacts of Ti-treated cells. Pyk2 phosphorylated on Tyr
      402 colocalized with paxillin in focal contacts of untreated cells, while it was
      barely detected upon exposure to particles. In summary, changes in the
      phosphorylation states of both FAK and Pyk2 tyrosine kinases at focal contacts
      underlie impaired bone-forming cell attachment after exposure to Ti particles of
      micrometric sizes.

PMID- 19861183
TI  - Nanosized and nanocrystalline calcium orthophosphates.
AB  - Recent developments in biomineralization have already demonstrated that nanosized
      crystals and particles play an important role in the formation of hard tissues of
      animals. Namely, it is well established that the basic inorganic building blocks
      of bones and teeth of mammals are nanosized and nanocrystalline calcium
      orthophosphates in the form of apatites. In mammals, tens to hundreds
      nanocrystals of a biological apatite have been found to be combined into self
      assembled structures under the control of bioorganic matrixes. Therefore,
      application and prospective use of the nanosized and nanocrystalline calcium
      orthophosphates for a clinical repair of damaged bones and teeth are also well
      known. For example, greater viability and better proliferation of various types
      of cells have been detected on smaller crystals of calcium orthophosphates. Thus,
      the nanosized and nanocrystalline forms of calcium orthophosphates have great
      potential to revolutionize the hard tissue-engineering field, starting from bone
      repair and augmentation to controlled drug delivery systems. This paper reviews
      the current state of art and recent developments of various nanosized and
      nanocrystalline calcium orthophosphates, starting from synthesis and
      characterization to biomedical and clinical applications. The review also
      provides possible directions for future research and development.

PMID- 19861184
TI  - Diamond-like carbon coatings enhance the hardness and resilience of bearing
      surfaces for use in joint arthroplasty.
AB  - The purpose of this study was to evaluate the potential of a hard diamond-like
      carbon (DLC) coating to enhance the hardness and resilience of a bearing surface
      in joint replacement. The greater hardness of a magnesium-stabilized zirconium
      (Mg-PSZ) substrate was expected to provide a harder coating-substrate composite
      microhardness than the cobalt-chromium alloy (CoCr) also used in arthroplasty.
      Three femoral heads of each type (CoCr, Mg-PSZ, DLC-CoCr and DLC-Mg-PSZ) were
      examined. Baseline (non-coated) and composite coating/substrate hardness was
      measured by Vickers microhardness tests, while nanoindentation tests measured the
      hardness and elastic modulus of the DLC coating independent of the Mg-PSZ and
      CoCr substrates. Non-coated Mg-PSZ heads were considerably harder than non-coated
      CoCr heads, while DLC coating greatly increased the microhardness of the CoCr and
      Mg-PSZ substrates. On the nanoscale the non-coated heads were much harder than on
      the microscale, with CoCr exhibiting twice as much plastic deformation as Mg-PSZ.
      The mechanical properties of the DLC coatings were not significantly different
      for both the CoCr and Mg-PSZ substrates, producing similar moduli of resilience
      and plastic resistance ratios. DLC coatings greatly increased hardness on both
      the micro and nano levels and significantly improved resilience and resistance to
      plastic deformation compared with non-coated heads. Because Mg-PSZ allows less
      plastic deformation than CoCr and provides a greater composite microhardness, DLC
      Mg-PSZ will likely be more durable for use as a bearing surface in vivo.

PMID- 19861186
TI  - Blood proteomics.

PMID- 19861185
TI  - NO-loaded Zn(2+)-exchanged zeolite materials: a potential bifunctional anti
      bacterial strategy.
AB  - Nitric oxide (NO) is important for the regulation of a number of diverse
      biological processes, including vascular tone, neurotransmission, inflammatory
      cell responsiveness, defence against invading pathogens and wound healing.
      Transition metal exchanged zeolites are nanoporous materials with high-capacity
      storage properties for gases such as NO. The NO stores are liberated upon contact
      with aqueous environments, thereby making them ideal candidates for use in
      biological and clinical settings. Here, we demonstrate the NO release capacity
      and powerful bactericidal properties of a novel NO-storing Zn(2+)-exchanged
      zeolite material at a 50 wt.% composition in a polytetrafluoroethylene polymer.
      Further to our published data showing the anti-thrombotic effects of a similar NO
      loaded zeolite, this study demonstrates the anti-bacterial properties of NO
      releasing zeolites against clinically relevant strains of bacteria, namely Gram
      negative Pseudomonas aeruginosa and Gram-positive methicillin-sensitive and
      methicillin-resistant Staphylococcus aureus and Clostridium difficile. Thus our
      study highlights the potential of NO-loaded zeolites as biocompatible medical
      device coatings with anti-infective properties.

PMID- 19861187
TI  - Successful seroresponses to measles and rubella following aerosolized Triviraten
      vaccine, but poor response to aerosolized mumps (Rubini) component: comparisons
      with injected MMR.
AB  - Seroresponses to measles, rubella and mumps were evaluated following the
      injection of MMR II and injection or aerosol administration of Triviraten in
      young adults. Response to aerosolized Rubini mumps strain was a focus of
      interest, given robust responses to aerosolized mumps vaccine (Leningrad-Zagreb
      strain) in a prior study using aerosolized MMR vaccine. The aerosolized Edmonston
      Zagreb (EZ) measles vaccine was significantly more immunogenic than injected EZ
      vaccine, and comparable to results following injected Moraten measles vaccine
      having twice the dosage. Responses to rubella were comparable in the three MMR
      study groups. Aerosolized Rubini vaccine was very highly and unexpectedly less
      immunogenic than either injected Rubini or Jeryl-Lyn strains. The high
      attenuation of Rubini vaccine appears to have limited its affinity for
      respiratory tract receptors, which may underlie its lack of clinical
      effectiveness.

PMID- 19861188
TI  - Going to the next level: health care's evolving expectations for evidence.
AB  - Rhinologic literature has historically relied on lower levels of evidence to make
      prescriptive recommendations for use of new technology and procedures. However,
      as the medical profession has moved to embrace the principles of evidence-based
      medicine, expectations for minimum standards of evidence have risen. The
      resulting high-quality efficacy outcomes data have become the linchpin of
      informed decision making by physicians, payers, and health care systems. While
      many challenges remain in this transition to higher evidence expectations, none
      are insurmountable. It has become the responsibility of the organized medical
      profession to play a role in influencing and supporting production of high
      quality outcomes research.

PMID- 19861189
TI  - Readability analysis of patient information on the American Academy of
      Otolaryngology-Head and Neck Surgery website.
AB  - OBJECTIVE: To evaluate the readability of patient-oriented online health
      information (OHI) presented on the American Academy of Otolaryngology-Head and
      Neck Surgery (AAO-HNS) website. STUDY DESIGN: Review of the Flesch-Kincaid (FK)
      grade level for 104 articles on the AAO-HNS website. METHODS: The FK grade level
      for 104 articles was determined using the readability calculator available within
      Microsoft Office Word 2003. The interobserver reliability for the FK grade level
      was determined by calculating the intraclass correlation coefficient (ICC) for 52
      entries. RESULTS: The average FK grade reading level of the articles was 10.8
      (range 6.3-16.7; 95% CI, 10.4-11.2). Eighty-one percent of the articles were
      written at a ninth grade level or higher. The intraclass correlation was good (r
      = 0.83) for the 52 articles that were independently reviewed. CONCLUSIONS: This
      analysis has shown that the average reading level for each article on the AAO-HNS
      site was higher than the recommended sixth grade reading level. Although the AAO
      HNS site is written at a higher level than that suggested for the general public,
      it is important to realize that readability is just one consideration in the
      evaluation of OHI comprehension. Physicians need to be cognizant of their
      patients' ability to read and comprehend written information and tailor their
      educational material appropriately.

PMID- 19861190
TI  - Pepsin as a causal agent of inflammation during nonacidic reflux.
AB  - OBJECTIVE: To investigate the contribution of pepsin to inflammation attributed
      to nonacidic gastric reflux via analysis of inflammatory cytokine and cytokine
      receptor gene expression in pepsin-treated human hypopharyngeal epithelial cells
      in vitro. STUDY DESIGN: Translational research. SETTING: This study was performed
      in an academic research laboratory. SUBJECTS AND METHODS: Human hypopharyngeal
      epithelial cells were incubated with or without pepsin (0.1 mg/mL) at pH 7.4, 37
      degrees C, overnight. Expression of 84 inflammatory cytokines and cytokine
      receptors was analyzed via RT(2) qPCR array. RESULTS: Expression of a number of
      inflammatory cytokines and receptors was altered in human hypopharyngeal
      epithelial cells following overnight treatment with pepsin at neutral pH. Greater
      than 1.5-fold change in gene expression was detected for CCL20, CCL26, IL8,
      IL1F10, IL1A, IL5, BCL6, CCR6, and CXCL14 (P < 0.05). CONCLUSION: Exposure of
      hypopharyngeal cells to pepsin in a nonacidic environment induces the expression
      of several pro-inflammatory cytokines and receptors, including those known to be
      involved in inflammation of esophageal epithelium in response to reflux and which
      contribute to the pathophysiology of reflux esophagitis. These data indicate that
      refluxed pepsin may contribute to laryngeal inflammation associated with
      nonacidic gastric reflux, including that experienced by patients despite maximal
      acid suppression therapy.

PMID- 19861191
TI  - Unexpected consequences of proton pump inhibitor use.
AB  - Proton pump inhibitors (PPIs) are among the most widely prescribed classes of
      medications for gastroesophageal and laryngopharyngeal reflux diseases. There is
      emerging evidence that the pathogenesis of disease in laryngeal mucosa is not
      just related to refluxed acid, but also the presence of pepsin and acidic
      microenvironments. The widespread use of PPIs is also calling into question
      potential complications of PPI use. This commentary expands upon these issues
      with other potential unexpected consequences, and considers the importance of
      determining a proper approach to patient management.

PMID- 19861192
TI  - Biofilm presence in humans with chronic suppurative otitis media.
AB  - OBJECTIVE: To study the presence of biofilm formation in humans with chronic
      suppurative otitis media (CSOM). STUDY DESIGN: Cross-sectional study. SETTING:
      Tertiary academic hospital. SUBJECTS AND METHODS: Patients undergoing middle ear
      surgery between July 2006 and March 2008. Tissue samples were obtained from 25
      patients, of which 20 specimens were successfully processed for this study. The
      remaining samples were not analyzed due to sample damage or loss during
      preparation. Of the 20 specimens studied, 10 were harvested as the experimental
      group from patients with CSOM and the other 10 harvested as controls from
      patients undergoing otologic surgery for acoustic neuroma, cochlear implant, or
      routine tympanoplasty. Ages ranged from 26 to 74 years (mean 45 yrs). Male-to
      female ratio was 2:3. Scanning electron microscopy and confocal laser scanning
      microscopy were used to identify the presence of biofilms. Live-dead staining was
      used to assess whether bacteria present were viable. The outcome measured was the
      presence of adherent biofilms on middle ear mucosa. RESULTS: Biofilms were
      present in six of 10 samples (60%) from the CSOM group, but only in one of 10
      control samples (10%). Comparative analysis revealed a statistically significant
      difference (P < 0.05) in the presence of biofilms in specimens from the CSOM
      group versus the control group. CONCLUSION: Biofilms were statistically more
      common in patients with CSOM compared with control patients.

PMID- 19861193
TI  - Clinical efficacy of initial intratympanic steroid treatment on sudden
      sensorineural hearing loss with diabetes.
AB  - OBJECTIVE: The purpose of this study is to compare the efficacy of intratympanic
      steroid injection (ITSI) with that of systemic steroids as an initial treatment
      of sudden sensorineural hearing loss (SNHL) with diabetes. STUDY DESIGN:
      Prospective, nonrandomized multicenter clinical trial. SETTING: Multicenter study
      in Busan and Masan, South Korea. SUBJECTS AND METHODS: A total of 114 sudden SNHL
      patients who were diagnosed with diabetes were divided into peroral (PO) group (n
      = 48), intravenous (IV) group (n = 32), and intratympanic (IT) group (n = 34). In
      the PO group, prednisolone was used orally for 10 days, per schedule. In the IV
      group, prednisolone was administered intravenously for seven days, followed by
      oral administration of tapered doses for another several days. In the IT group,
      dexamethasone was injected into the tympanic cavity four times within a two-week
      period. Hearing outcome was assessed before and after the treatment. RESULTS: All
      groups showed significant improvement with criteria of 15 dB (P < 0.05). However,
      there was no significant difference in hearing gain and recovery rate among
      groups (P > 0.05). Systemic steroid treatment was stopped for two patients in the
      IV group and for one in the PO group due to uncontrolled hyperglycemia. However,
      in the IT group, there were no patients who failed to control their blood sugar
      level. CONCLUSION: ITSI is as effective as systemic steroid treatment for sudden
      SNHL patients with diabetes and it can avoid undesirable side effects. Therefore,
      we consider ITSI to be a more reasonable alternative as an initial treatment for
      sudden SNHL patients with diabetes.

PMID- 19861194
TI  - Hearing outcomes of daily intratympanic dexamethasone alone as a primary
      treatment modality for ISSHL.
AB  - OBJECTIVE: Intratympanic (IT) dexamethasone offers a good method for avoiding
      systemic side effects in patients with sudden idiopathic sensorineural hearing
      loss (ISSHL). However, in most studies, IT was used as a salvage treatment for
      patients whose hearing failed to improve with the initial systemic treatment, or
      as an addition to conventional oral steroid protocols. Therefore, we investigated
      the outcomes of IT steroid administration as a primary treatment modality for
      ISSHL. STUDY DESIGN: Randomized controlled study. SETTING: Tertiary referral
      center. SUBJECTS AND METHODS: Two treatment methods, IT dexamethasone or oral
      prednisolone, were randomly assigned to 63 participants. A group of 32 patients
      (IT group) with ISSHL received IT dexamethasone once a day for eight days. A
      separate group of 31 patients (oral group), received oral prednisolone, also for
      eight days. We compared the hearing outcomes in the two groups. RESULTS: We have
      found that the outcomes for patients treated with IT dexamethasone as a primary
      treatment modality for the management of ISSHL presented no difference in pure
      tone averages or hearing recovery rate compared with patients treated with oral
      steroids. However, differences were noted for hearing thresholds according to
      frequency: the threshold improvement at low frequencies (250, 500, and 1000 Hz)
      was not statistically significant between groups; at high frequencies,
      particularly 4000 and 8000 Hz, the threshold improvement was statistically higher
      in the oral group than in the IT group. CONCLUSION: IT dexamethasone might be a
      good primary treatment method for ISSHL; but, for the management of ISSHL, we
      should keep in mind the differences in hearing outcomes with regard to frequency.

PMID- 19861195
TI  - Direct drug application to the round window: a comparative study of ototoxicity
      in rats.
AB  - OBJECTIVE: To assess the validity of inducing ototoxicity in rats by applying a
      sponge soaked in kanamycin and furosemide on the round window. STUDY DESIGN:
      Basic, randomized, nonblind experimental study. SETTING: Animal models of
      cochlear damage and reliable methods of local drug delivery are fundamental to
      study hearing loss and to design new therapies. SUBJECTS AND METHODS: Four
      experimental groups of six Wistar rats with different methods of drug
      administration were used: (1) injection of subcutaneous kanamycin (400 mg/kg) and
      intravenous furosemide (100 mg/kg); (2) local application of a sponge soaked in
      saline close to the round window; (3) animals for which the sponge was soaked in
      a solution containing kanamycin (200 mg/mL) and furosemide (50 mg/mL); and (4)
      sham-operated rats. The tympanic bulla was exposed using a ventral approach, and
      a bullostomy was performed to visualize the round window membrane. Cochlear
      function was assessed by measuring the auditory brainstem response, and hearing
      thresholds in response to click and tone burst stimuli were determined as peak
      and interpeak latencies. At the end of the study, cochlear histology was
      analyzed. RESULTS: Systemic administration of kanamycin and furosemide induced
      profound hearing loss and severe hair cell damage. Local delivery of these
      ototoxic drugs caused comparable damage but avoided the systemic side effects of
      the drug. Sham-operated and saline control animals did not experience functional
      alterations. CONCLUSION: Situating a sponge soaked in kanamycin and furosemide on
      the round window membrane through the ventral approach is a reliable method to
      provoke local ototoxicity in rats.

PMID- 19861196
TI  - Complications/adverse effects of maxillomandibular advancement for the treatment
      of OSA in regard to outcome.
AB  - OBJECTIVE: To evaluate adverse effects/postoperative complications and surgical
      response rate of maxillomandibular advancement for the treatment of severe
      obstructive sleep apnea syndrome. STUDY DESIGN: Case series with chart review.
      SETTING: Otolaryngology Head and Neck Surgery Department in a teaching hospital.
      SUBJECTS AND METHODS: A total of 59 consecutive severe sleep apnea patients
      underwent maxillomandibular advancement. Systemic complications were evaluated
      from medical charts. Functional adverse effects and cosmetic consequences were
      evaluated by questionnaires. The treatment outcome was assessed by
      polysomnography. RESULTS: Fifty patients were evaluated. They had a mean age of
      46.4 +/- 9.0 years. No serious postoperative complication was observed. The most
      frequent local complication was mental nerve sensory loss. Most patients reported
      cosmetic changes. The mean apnea-hypopnea index decreased from 65.5 +/- 26.7 per
      hour to 14.4 +/- 14.5 per hour (P < 0.0001). Light-sleep stages were also
      decreased (P < 0.0001), whereas deep-sleep stages were increased (P < 0.001).
      CONCLUSION: Maxillomandibular advancement can induce local adverse effects and
      cosmetic changes, but they seem to be considered as secondary to the patients
      according to the surgical outcome.

PMID- 19861197
TI  - In vitro testing of tympanostomy tube occlusion.
AB  - OBJECTIVE: Tympanostomy tubes (TTs) are commonly rendered nonfunctional by mucus
      plug formation. The purpose of this study was to determine whether an in vitro
      model could be developed to assess TT plug formation with results consistent with
      human trials. STUDY DESIGN: An ear chamber was designed to mimic middle ear air
      and mucus flow conditions in post-TT otorrhea. TT occlusion was tested and
      correlated to published in vivo results. METHODS: TTs that had previously been
      studied in vivo (Goode "T" and Reuter Bobbin collar buttons) were placed in the
      model chamber. Pooled, homogenized human middle ear mucus and an analog, egg
      white, were delivered at 80 muL per hour through the TTs. An air bolus was
      delivered every two minutes to simulate swallowing. Chamber pressure was
      monitored over 2.5 hours. Occlusion was determined by a pressure peak and visual
      confirmation. RESULTS: Obstruction was found in 60 percent of the Reuter Bobbin
      and 40 percent of the Goode TTs using the mucus analog. These results are similar
      to those reported from previous in vivo studies. No plugging was reported for
      either TT using homogenized human ear mucus. CONCLUSIONS: The in vitro TT chamber
      simulates the in vivo environment and yields results consistent with in vivo
      observations. This model system may allow for rapid prototyping and evaluation of
      new TTs that may be less vulnerable to occlusion.

PMID- 19861198
TI  - Construct validity of a simulator for myringotomy with ventilation tube
      insertion.
AB  - OBJECTIVES: To establish construct validity of an anatomic model as a simulator
      for myringotomy with ventilation tube insertion and to assess its subjective
      appeal. STUDY DESIGN: Cross-sectional, repeated-measures comparative evaluation
      of simulator. SETTING: University academic otolaryngology residency program.
      SUBJECTS AND METHODS: Using an anatomic model of the human auricle, ear canal,
      eardrum, and middle ear space, 18 otolaryngologists of various levels of training
      performed 10 timed procedures: myringotomy with ventilation tube insertion.
      Errors were recorded, and participants reported the quality of their experience.
      RESULTS: Both time-to-completion and errors per trial discriminated novices from
      non-novice participants; novices (02:23, 95% confidence interval [CI], 01:42
      03:04) were 3.6 times slower than non-novices (00:39, 95% CI, 00:35-00:43) and
      6.5 times more error prone (novices 2.16 errors/trial, 95% CI, 1.68-2.64; non
      novices 0.33 errors/trial, 95% CI, 0.21-0.45). Errors were strongly correlated
      with prior surgical experience. All participants required more time to complete
      the first trial, and their performance stabilized thereafter. Overall, the
      simulation was perceived as a valuable experience. CONCLUSION: Our model is a
      valid platform for simulating myringotomy with ventilation tube insertion. The
      model discriminates novices from non-novices, has a learning curve, and is
      perceived to be a valuable and realistic teaching tool by users.

PMID- 19861199
TI  - Oropharyngeal flora changes after tonsillectomy.
AB  - OBJECTIVE: We aimed to investigate the effect of tonsillectomy on oropharyngeal
      flora in children who underwent tonsillectomy for chronic recurrent tonsillitis.
      STUDY DESIGN AND SETTING: A prospective study was performed comprising patients
      with chronic recurrent tonsillitis who underwent tonsillectomy at the Department
      of Otolaryngology, Cerrahpasa Medical School. Incisional core biopsies of excised
      tonsils were also performed. Swabs and core biopsy specimens were transferred and
      maintained in Stuart's medium and sent to the Department of Microbiology and
      Clinical Microbiology at Cerrahpasa Medical School for microbiologic evaluation.
      SUBJECTS AND METHODS: Oropharyngeal swabs and tonsillar core biopsy specimens
      from 31 patients operated on for recurrent tonsillitis were cultured. Follow-up
      oropharyngeal swabs were cultured one month after tonsillectomy. RESULTS: There
      was no significant difference between the preoperative and postoperative
      isolation rate of the potentially pathogenic bacteria. Normal aerobic flora did
      not change significantly. However, the isolation rate of the Neisseria species
      dropped (P = 0.097) but did not reach statistical significance. Among anaerobes,
      Bacteroides fragilis, one of the major anaerobic bacteria, dropped significantly
      (P = 0.007). The Propionibacterium acnes isolation rate increased significantly
      (P = 0.009). CONCLUSION: Oropharyngeal anaerobic bacterial flora decreases after
      tonsillectomy in recurrent tonsillitis patients. The isolation rate for bacteria
      of the normal flora and potentially pathogenic bacteria does not change. Tonsils
      with recurrent infections may become a nidus for anaerobic bacteria. In patients
      with chronic recurrent tonsillitis, tonsillectomy may help change anaerobic
      bacterial oropharyngeal flora to the normal flora found in healthy individuals.

PMID- 19861200
TI  - Volume and distances of the maxillary sinus in craniofacial deformities with
      midfacial hypoplasia.
AB  - OBJECTIVE: Craniofacial deformities (CFDs) frequently accompany midfacial
      hypoplasia. The authors evaluated characteristics of maxillary sinuses that had
      CFDs with variable degrees of midfacial hypoplasia. STUDY DESIGN: Cross-sectional
      survey with chart review. SETTING: Department of Plastic and Reconstructive
      Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul,
      Republic of Korea. SUBJECTS AND METHODS: We investigated 40 patients with CFDs
      having midfacial hypoplasia. Study group 1 (SG 1) consisted of eight patients
      with Crouzon syndrome (16 maxillary sinuses). Study group 2 (SG 2) consisted of
      10 patients with midfacial hypoplasia after palatoplasty (20 maxillary sinuses).
      Study group 3 (SG 3) consisted of 22 patients with Pruzansky grade I hemifacial
      microsomia (22 maxillary sinuses on the affected sides). Data on volume and three
      dimensional distances (height, width, and depth) from computed tomography were
      collected and compared with each corresponding control group. Correlation
      coefficient between volume and the three distances was also calculated. RESULTS:
      The volume, height, width, and depth of the maxillary sinus were significantly
      decreased in SG 1 (P < 0.01). In SG 2, only the depth was significantly decreased
      (P < 0.05). In SG 3, there were no significant differences in any parameters. A
      multiple-regression analysis between the volume and the three distances showed a
      statistically significant relationship for width in SG 1, width and height in SG
      2, and all distances in SG 3. CONCLUSION: There were differences in the structure
      of the maxillary sinuses among patients with different CFDs.

PMID- 19861201
TI  - Postoperative monitoring in free tissue transfer patients: effective use of
      nursing and resident staff.
AB  - OBJECTIVES: To compare the outcomes of two different free flap monitoring
      protocols and determine whether nursing staff can safely and effectively monitor
      free flaps. STUDY DESIGN: Historical cohort study on all head and neck free
      tissue transfer patients from August 2003 to August 2007. SETTING: Tertiary care
      teaching institution. SUBJECTS AND METHODS: The patients were divided into two
      groups according to monitoring protocol. Group A (n = 49) had free flaps
      monitored primarily by resident physicians, while Group B patients (n = 45) were
      evaluated primarily by nursing staff. Demographic and outcomes data, including
      complications, reoperations, length of hospital stay, and flap viability, were
      then compared. RESULTS: Overall, 28 (57%) patients in Group A and 16 (37%) in
      Group B had at least one complication (P = 0.05). Only eight patients in each
      group had major complications. There were 25 (27%) patients who required further
      intervention in the operating room: 18 (37%) in Group A and seven (16%) in Group
      B (P = 0.03). Only 12 (13%) patients returned to the operating room for concerns
      of flap viability: seven from Group A and five from Group B. The median length of
      hospital stay was 11 days for both groups (P = 0.76). The flap success rate was
      95 percent, with three failures in Group A and two in Group B (P = 0.72).
      CONCLUSIONS: A monitoring protocol utilizing trained nursing staff has no
      detrimental effect on free tissue transfer outcomes. This may be used to optimize
      resident time within the current duty-hour restrictions.

PMID- 19861202
TI  - 2D-DIGE proteomic characterization of head and neck squamous cell carcinoma.
AB  - OBJECTIVE: Identify proteins that are differentially expressed between head and
      neck squamous cell cancer (HNSCC) and patient-matched normal adjacent tissue, and
      validate findings in a separate patient cohort. STUDY DESIGN: Cross-sectional
      study of surgical specimens. SETTING: Tertiary care academic medical center.
      SUBJECTS AND METHODS: Laser capture microdissection and two-dimensional
      difference gel electrophoresis were used previously to establish proteomic
      profiles for tumor and normal adjacent tissue from 14 patients. Here,
      significance analysis of microarray was used to rank candidate biomarkers. Spots
      meeting statistical and biological criteria of significance were analyzed by
      liquid chromatography and tandem mass spectrometry to obtain protein
      identifications. The expression pattern of the highest-ranked candidate biomarker
      (cornulin) was validated in a larger, independent patient cohort (n = 68) by
      immunohistochemical staining of a tissue microarray. RESULTS: Of 732 spots, 117
      (15.9%) met criteria for significance. Identities were obtained for 39 spots,
      representing 17 different proteins. Four proteins were novel in the context of
      HNSCC: glutathione synthetase, which was upregulated; and cornulin (squamous
      epithelial heat shock protein 53), guanylate binding protein 6, and heat shock 70
      kDa protein 5 (glucose-regulated protein, 78 kDa), which were downregulated.
      Cornulin functions in the stress response in normal squamous epithelium, and
      reduced expression has been proposed as a marker of susceptibility to
      laryngopharyngeal reflux and other stressors. Loss of cornulin expression was
      confirmed in an independent HNSCC patient cohort (P < 0.001). CONCLUSIONS:
      Downregulation of cornulin is a prominent feature of the molecular signature of
      HNSCC identified by comparative proteomics. Cornulin may represent a link between
      HNSCC and other pathologies arising in stratified squamous epithelium.

PMID- 19861203
TI  - Additional diagnostic value of (18)F-FDG PET-CT in detecting retropharyngeal
      nodal metastases.
AB  - OBJECTIVE: This study investigated whether preoperative (18)fluorine
      fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT)
      scanning improved the diagnosis of retropharyngeal lymph node (RPLN) metastasis
      in patients with head and neck squamous cell carcinoma (HNSCC) relative to
      conventional imaging alone. STUDY DESIGN: Case series with chart review. SETTING:
      University hospital cancer center. SUBJECTS AND METHODS: Sixty-three patients
      with HNSCC underwent RPLN dissection in accordance with our indications and were
      subsequently divided into two groups: CT/magnetic resonance imaging (MRI) only
      (group A, n = 33) and CT/MRI with PET-CT (group B, n = 30). The preoperative
      radiological findings of each group were compared with the RPLN histopathologic
      findings, which served as the standard of reference. RESULTS: RPLN metastasis was
      confirmed histopathologically in 17 of 63 patients (27.0%): eight from group A
      and nine from group B. With the additional use of PET-CT in group B, the
      sensitivity (88.9%), specificity (85.7%), and accuracy (86.7%) were higher than
      the respective values in group A (62.5%, 60.0%, and 60.6%). The positive and
      negative predictive values for group B (72.7% and 94.7%, respectively) were also
      higher than those for group A (33.3% and 83.3%, respectively). False-positive
      results were obtained in 10 patients from group A and three patients from B;
      false-negative findings occurred in three patients from group A and one patient
      from group B. The predictive power of the radiological findings was statistically
      significant in group B (P = 0.0017), with an odds ratio of 47.987 (95% confidence
      interval, 4.3-535.0). CONCLUSION: (18)F-FDG PET-CT, when used in combination with
      CT/MRI, increases diagnostic efficacy in the detection of RPLN metastases and may
      therefore be useful in screening high-risk patients.

PMID- 19861205
TI  - Prevention of unplanned pharyngocutaneous fistula in salvage laryngectomy.

PMID- 19861204
TI  - Anatomical variations of the spinal accessory nerve and its relevance to level
      IIb lymph nodes.
AB  - OBJECTIVE: This study was conducted to identify anatomical variations of the
      spinal accessory nerve (SAN) in the upper neck, the landmark of the anterior and
      inferior border of level IIb, and to evaluate the nerve's effect on the border
      and the number of lymph nodes (LNs) in level IIb. STUDY DESIGN AND SETTING: Case
      series with planned data collection. SUBJECTS AND METHODS: A total of 181 neck
      dissections (NDs) were prospectively enrolled in this study. The relation between
      the SAN and adjacent structures (internal jugular vein [IJV], sternocleidomastoid
      muscle [SCM], cervical plexus) and the number of LNs in level IIb was
      investigated. RESULTS: The SAN crossed the IJV ventrally in 72 cases (39.8%) and
      dorsally in 104 cases (57.4%), and passed through the IJV in five cases (2.8%).
      The SAN ran along the inner surface of the SCM and sent branches to the SCM
      without penetration of the muscle in 83 cases (45.9%), whereas in 98 cases
      (54.1%) the nerve sent branches to the SCM by penetration. Cervical plexus
      contribution to the SAN was seen from C2 in 96 cases (53.1%), C2 and C3 in 69
      cases (38.1%), and C3 in 16 cases (8.8%). The mean number of LNs of level IIa and
      level IIb was 6.5 and 8.2 in cases in which the SAN crossed the IJV ventrally,
      and 6.8 and 5.4 in dorsally crossing cases. LNs included in the neck level IIb in
      ventrally crossing SAN cases were significantly larger than the dorsally crossing
      cases (P < 0.05). CONCLUSIONS: Our results may help to minimize the incidence of
      injuring the SAN in the upper neck during ND. Neck level IIb would contain more
      LNs if the course of the nerve leans toward the ventral side.

PMID- 19861207
TI  - Penetrating facial injury from a wooden chopstick.

PMID- 19861206
TI  - Modification of the mandibular genial osteotomy for "drop down" access to the
      base of the tongue.

PMID- 19861208
TI  - Isolated fracture of the malleus handle.

PMID- 19861209
TI  - Fibrous dysplasia of the temporal bone presenting as an external auditory canal
      mass.

PMID- 19861210
TI  - Donor site metastasis after pectoralis major myocutaneous flap reconstruction for
      oral squamous cell carcinoma.

PMID- 19861211
TI  - Sudden deafness as a presenting symptom of chronic hepatitis B with acute
      exacerbation.

PMID- 19861212
TI  - Management of closed tracheal perforation following blunt trauma.

PMID- 19861213
TI  - Angioleiomyoma of the nasal cavity: a rare cause of epistaxis.

PMID- 19861214
TI  - Diabetes education...or the lack thereof.

PMID- 19861215
TI  - The elusive low vision patient.

PMID- 19861216
TI  - Infection control guidelines--an update for the optometric practice.

PMID- 19861217
TI  - Bitemporal hemianopia arising from a suprasellar craniopharyngioma.
AB  - BACKGROUND: Craniopharyngiomas are uncommon intracranial tumors that arise from
      remnants of the embryonic craniopharyngeal duct. Although benign in nature,
      craniopharyngiomas can contribute to significant morbidity. When located near
      critical structures such as the optic chiasm, pituitary, and hypothalamus,
      craniopharyngiomas have the potential to cause severe visual, neurological, and
      endocrine deficits. CASE REPORT: A 61-year-old white man presented for an eye
      examination, complaining of acute peripheral visual field loss in his left eye.
      Automated threshold visual field testing found a bitemporal hemianopia with
      spared fixation in his right eye and split fixation in his left eye. Subsequent
      neuroimaging found a space-occupying suprasellar lesion that was producing
      substantial optic chiasm compression. Transsphenoidal resection was used to
      excise the mass. Histologic examination established the diagnosis of a
      craniopharyngioma. Postoperative complications included cerebrospinal rhinorrhea,
      hypertropia, and exotropia. CONCLUSION: To facilitate early diagnosis and
      treatment, eye care professionals should be aware that craniopharyngiomas can
      present with decreased visual acuity and bitemporal hemianopia. Visual deficits
      can arise from both the aggressive nature of craniopharyngiomas as well as the
      therapeutic intervention. Patients treated for craniopharyngiomas are at risk for
      recurrence and need to be followed up on a long-term basis.

PMID- 19861218
TI  - Does the dynamic cross cylinder test measure the accommodative response
      accurately?
AB  - BACKGROUND: The dynamic cross cylinder (DCC) test is a standard clinical
      procedure used to assess the accommodative response (AR) subjectively. However,
      because of potential problems arising from the ambiguous stimulus conditions, it
      is unclear whether this test provides an accurate measure of the AR. The aim of
      this study was to compare clinical subjective findings with objective
      measurements of the AR. METHODS: Subjective findings to a 2.50-diopter (D)
      accommodative stimulus obtained with the DCC test (without fogging lenses) were
      compared with objective measurements of the AR obtained with a Grand Seiko WAM
      5500 optometer (RyuSyo Industrial Co. Ltd., Kagawa, Japan) in 25 young subjects.
      As spherical lenses were introduced to quantify the subjective finding, objective
      measures of the AR were also recorded through these lenses. RESULTS: The mean AR
      recorded subjectively and objectively was 2.35 and 1.68 D, respectively (P <
      0.0001). Of the 10 subjects who demonstrated a lead of accommodation
      subjectively, only 1 had a lead objectively. For the 8 subjects who showed a lag
      of accommodation subjectively, all had a lag objectively. Introducing lenses
      produced a significant change in the mean AR. CONCLUSION: The subjective DCC test
      as performed here does not provide an accurate measurement of the AR to a near
      target in a young population. We recommend that alternative techniques such as
      using an objective, open-field optometer or Cross-Nott retinoscopy be adopted for
      determining the within-task AR.

PMID- 19861219
TI  - Brain-derived neurotrophic factor in patients with normal-tension glaucoma.
AB  - PURPOSE: The aim of this study was to detect and measure brain-derived
      neurotrophic factor (BDNF) in the tears of normal subjects and patients with
      normal-tension glaucoma (NTG). MATERIALS AND METHODS: Twenty patients with NTG as
      the case group and 20 normal subjects with the same age range as the control
      group were tested. The control group consisted of 16 men and 4 women, ranging in
      age from 40 to 75, without any apparent ocular or systemic disease. The case
      group consisted of 15 men and 5 women, ranging in age from 45 to 74. BDNF levels
      in tears were determined by enzyme-linked immunosorbent assay using monoclonal
      antibodies specific for BDNF (R&D Systems, Minneapolis, Minnesota). RESULTS: The
      mean level of BDNF detected in the tears of the normal subjects was 77.09 +/-
      4.84 ng/mL and the BDNF levels in the tears of case group were 24.33 +/- 1.48
      ng/mL (P < 0.001). CONCLUSION: We suggest that BDNF in the tears might be a
      useful biochemical marker for early detection of normal-tension glaucoma (NTG).

PMID- 19861220
TI  - Refractive error and axial length in nonarteritic anterior ischemic optic
      neuropathy.
AB  - PURPOSE: The aim of this study was to evaluate the ocular axial length and
      refractive error as risk factors for development of nonarteritic anterior
      ischemic optic neuropathy (NAION). METHODS: This prospective study included 78
      patients with NAION and 80 normal volunteers. Axial length and refractive error
      of NAION eyes were compared with the normal fellow eyes and control eyes.
      RESULTS: The 2 groups were frequency matched by sex and age. The mean refractive
      error (in spherical equivalent) was -0.07 +/- 1.60 diopters (D) in NAION eyes,
      0.00 +/- 1.6 D in normal fellow eyes (P = 0.7), and -0.04 +/- 1.1 D in control
      eyes (P = 0.9). No significant difference was found between axial length
      measurements of NAION eyes (22.86 +/- 0.82 mm) and fellow eyes (22.80 +/- 0.88
      mm; P = 0.8) and control eyes (23.1 +/- 0.78 mm; P = 0.1). Most of the NAION eyes
      (50%) were emmetropic (between +0.5 and -0.5 D). CONCLUSION: Axial length and
      refractive error may not be risk factors in NAION.

PMID- 19861222
TI  - The Elder's Right to Sight Collaborative: a new model of eye care delivery for
      the elderly.
AB  - Vision and visual impairment have a significant impact on older adults' daily
      function and safety within their homes and communities. Yet many do not seek out
      the necessary care to address their visual health. Many older adults want to age
      in places that require a supportive environment to compensate for changes in
      abilities and to promote healthy aging and quality of life. The Elder's Right to
      Sight Collaborative (ERTS) was established to gain insight into the role of the
      environment in maintaining the functional independence and safety of older adults
      with visual impairment and to understand the barriers to obtaining the necessary
      eye care services. The ERTS provides education, screening, environmental
      assessments, and simple tools to complete daily activities. The screening results
      indicate significant need for eye care services to this population. However,
      service delivery needs to be flexible to meet the needs of this population. A
      team approach to address education, eye care services, rehabilitation,
      environmental assessment, and social services is needed. Through education,
      accessible services, rehabilitation, and environmental modifications, a
      significant impact on an older adult's independence and quality of life can be
      attained.

PMID- 19861221
TI  - Foveal versus eccentric retinal critical flicker frequency in mild traumatic
      brain injury.
AB  - BACKGROUND: The purpose of this study was to assess the critical flicker fusion
      frequency (CFF) at the fovea and at 10 degrees of horizontal retinal eccentricity
      and to determine if there was a correlation between CFF and the degree of light
      and motion sensitivity in individuals with mild traumatic brain injury (TBI).
      METHODS: Mean CFF thresholds at the fovea, and 10 degrees to the left and right
      of the fovea, were obtained in 14 mild TBI and 29 visually normal subjects. A
      questionnaire was used to quantify the degree of light and motion sensitivity and
      related factors. RESULTS: There was no effect of age on CFF under any test
      condition in either group, nor was there a relation in the TBI group between
      reported light or motion sensitivity and CFF. Peripheral CFF values were lower in
      both populations. Among the TBI subjects, there was a trend for lower peripheral
      CFF values in the periphery and greater mean variability under all 3 test
      conditions. CONCLUSIONS: Decreased sensitivity and increased variability in CFF
      measurements in the TBI population can be attributed to damage to the higher
      visual pathways.

PMID- 19861223
TI  - Estimating thermo-osmotic coefficients in clay-rocks: II. In situ experimental
      approach.
AB  - Water flow in compacted shales is expected to be modified by thermo-osmosis when
      a thermal gradient exists. However this coupled-flow process is poorly
      characterized since no experiments on non-remoulded clay-rocks are found in the
      literature. This paper presents a set of thermo-osmosis experiments carried out
      in an equipped borehole installed in the Liassic argillite at the Institut for
      Radiological protection and Nuclear Safety (IRSN) underground research laboratory
      (URL) of Tournemire (southeastern France). A numerical model - including coupled
      flow equations, mass conservation laws, thermal expansion and changes of water
      properties with temperature - was developed for the interpretation of these
      experiments. A thermo-osmotic response was deduced from the pressure evolution in
      the test interval after temperature pulses (+2.5, +5.1, and +9 degrees C). The
      values of thermo-osmotic permeability determined during the experiments range
      between 6x10(-12) and 2x10(-10)m(2)K(-1)s(-1), depending on the pulse temperature
      and uncertainties on the model parameters. A sensitivity analysis on several
      model parameters was performed to constrain these uncertainties.

PMID- 19861224
TI  - Processing of SeMV polyproteins revisited.
AB  - Processing of Sesbania mosaic virus (SeMV) polyprotein 2a and 2ab was reanalyzed
      in the view of the new genome organization of sobemoviruses. Polyprotein 2a when
      expressed in E. coli, from the new cDNA clone, got cleaved at the earlier
      identified sites E325-T326, E402-T403 and E498-S499 to release protease, VPg, P10
      and P8, respectively. Additionally, a novel cleavage was identified within the
      protease domain at position E132-S133, which was found to be essential for
      efficient polyprotein processing. Products, corresponding to cleavages identified
      in E. coli, were also detected in infected Sesbania leaves. Interestingly, though
      the sites are exactly the same in polyprotein 2ab, it got cleaved between
      Protease-VPg but not between VPg-RdRp. This indicates to a differential cleavage
      preference, governed probably by the conformation of 2ab. Also, the studies
      revealed that, in SeMV, processing is regulated by mode of cleavage and context
      of the cleavage site.

PMID- 19861226
TI  - Sexual problems after breast cancer: the underreported symptoms.

PMID- 19861225
TI  - Nucleolin/Nsr1p binds to the 3' noncoding region of the tombusvirus RNA and
      inhibits replication.
AB  - Previous genome-wide screens identified >100 host genes affecting tombusvirus
      replication using yeast model host. One of those factors was Nsr1p (nucleolin),
      which is an abundant RNA-binding shuttle protein involved in rRNA maturation and
      ribosome assembly. We find that overexpression of Nsr1p in yeast or in Nicotiana
      benthamiana inhibited the accumulation of tombusvirus RNA by approximately 10
      fold. Regulated overexpression of Nsr1p revealed that Nsr1p should be present at
      the beginning of viral replication for efficient inhibition, suggesting that
      Nsr1p inhibits an early step in the replication process. In vitro experiments
      revealed that Nsr1p binds preferably to the 3' UTR in the viral RNA. The purified
      recombinant Nsr1p inhibited the in vitro replication of the viral RNA in a yeast
      cell-free assay when preincubated with the viral RNA before the assay. These data
      support the model that Nsr1p/nucleolin inhibits tombusvirus replication by
      interfering with the recruitment of the viral RNA for replication.

PMID- 19861227
TI  - Anti-angiogenesis agents in metastatic or recurrent cervical cancer.
AB  - While the incidence of cervical cancer has declined significantly in the United
      States, it still remains a serious American health threat. When detected early,
      cervical cancer is generally curable. Early lesions are treated surgically, and
      locally advanced lesions are managed with concurrent cisplatin chemotherapy and
      pelvic radiation. Metastatic disease or recurrent lesions not amenable to radical
      local excision or regional radiation are treated with palliative chemotherapy.
      Current chemotherapeutic regimens are associated with significant side effects
      and only limited activity making the identification of active and tolerable novel
      targeted agents a high priority. Angiogenesis is central to cervical cancer
      development and progression. The dominant role of angiogenesis in cervical cancer
      seems to be directly related to HPV inhibition of p53 and stabilization of HIF-1
      alpha, both of which increase VEGF. Bevacizumab binding and subsequent
      inactivation of VEGF seem to shrink cervical tumors and delay progression without
      appreciable toxicity, and are therefore being studied in a Gynecologic Oncology
      Group (GOG) phase III trial. Other intracellular tyrosine kinase inhibitors
      (TKIs) of angiogenesis such as pazopanib are also encouraging, especially in lieu
      of their oral administration. Further study of angiogenesis and its inhibition
      are ongoing.

PMID- 19861228
TI  - Cognitive and anxiety symptoms in screening for clinical depression in diabetes:
      a systematic examination of diagnostic performances of the HADS and BDI-SF.
AB  - BACKGROUND: Little systematic research into the diagnostic performance of
      instruments used to screen for clinical depression is available for people with
      diabetes. The objective of this study was to compare performances of the HADS and
      BDI-SF and their components in association with a standard diagnostic interview.
      METHODS: In a sample of 298 French outpatients from a diabetes clinic (165 men,
      aged 59.4 + or - 10.7 years), we assessed diagnoses of clinical depression (CD,
      n=42) and major depression (MD, n=30) using the MINI and administered the HADS
      and BDI-SF. RESULTS: Cognitive symptoms from the BDI-SF (BDIcog) were more
      closely associated with MD than CD. BDIcog and HADS total scores performed best
      overall in identifying clinical depression (AUCs under ROC curve 85%). For
      identification of CD, the sensitivity/specificity of BDI cognitive symptoms was
      88/71% (cutoff 3+) and for the HADS 83/65% (cutoff 13+). For identification of
      MD, BDIcog scored 83/80% (cutoff 4+) and HAD-A 80/76% (cutoff 9+). Logistic
      regression analyses further suggested that BDIcog and HAD-A discriminated between
      depressed and non-depressed patients better than the somatic and anhedonia items
      present in the same scales. The depression subscale of the HADS performed poorly.
      LIMITATIONS: The consecutive nature of the sample may limit the generalizability
      of our findings. CONCLUSION: Results suggest that, in addition to depressed mood,
      both negative thoughts and anxiety are core elements for the correct
      identification of clinical depression in chronic illnesses such as diabetes. It
      may be more appropriate to use the total score when applying the HADS and
      distinguish non-somatic symptoms within the BDI.

PMID- 19861229
TI  - A comparison between monophasic and biphasic defibrillation for the cardioversion
      of persistent atrial fibrillation in patients with and without heart failure.
AB  - AIMS: Atrial fibrillation (AF) and heart failure commonly coexist. Restoring
      sinus rhythm using external direct current cardioversion (DCCV) may improve left
      ventricular function, exercise capacity and quality of life (QoL). However, DCCV
      may be less successful at restoring sinus rhythm in patients with heart failure.
      We aimed to determine whether biphasic DCCV was superior to monophasic DCCV for
      the restoration of sinus rhythm in patients with heart failure. METHODS: 592
      consecutive cardioversion procedures were performed on 503 patients for
      persistent AF, 261 (44%) procedures using monophasic defibrillation and 331 (56%)
      using biphasic. Patients with symptomatic heart failure were identified for
      further analysis. RESULTS: 173 cardioversions were performed on 149 patients with
      heart failure. The overall success rate of cardioversion in this group was 82.7%
      (83.3% and 82.2% for monophasic and biphasic respectively). There was no
      difference in the success rate of cardioversion for those with heart failure
      compared to those without heart failure (p = 0.141). Furthermore, there was no
      substantial difference in success rates according to defibrillation type (83.3%
      v. 84.2% for monophasic and 82.2% v. 88.5% for biphasic, p = 0.502 and 0.085
      respectively). CONCLUSION: External defibrillation is similarly effective at
      restoring SR in patients with and without HF and both mono- and biphasic shocks
      have a high rate of success. However, significantly less energy (maximal and
      cumulative) is required to restore SR using biphasic defibrillation.

PMID- 19861230
TI  - Bioactive alginate coatings to control Listeria monocytogenes on cold-smoked
      salmon slices and fillets.
AB  - The relatively high incidence of Listeria monocytogenes in cold smoked salmon
      (CSS) is of concern as CSS is a ready-to-eat product. No post-processing measures
      are currently available to control this pathogen in CSS. The objective of this
      study was to develop an effective antimicrobial edible coating containing organic
      salts to control the growth of L. monocytogenes in CSS slices and fillets. An in
      house made formulation consisting of sodium lactate (SL, 0-2.4%) and sodium
      diacetate (SD, 0-0.25%) as well as 2.5% OptiForm (a commercial formulation of SL
      and SD) were incorporated into five edible coatings: alginate, kappa-carrageenan,
      pectin, gelatin or starch. The coatings were applied onto the surface of CSS
      slices inoculated with L. monocytogenes to an inoculum level of 500 CFU/cm(2) (
      approximately 3 log CFU/g) and stored at room temperature (22 degrees C) for 6
      days. Alginate coating was found to be the most effective carrier for the various
      antimicrobial treatments in inhibiting the growth of L. monocytogenes. In the
      second phase of the study, CSS slices and fillets inoculated with the pathogen at
      a level of 500 CFU/cm(2) were coated with alginate incorporating the in-house
      made and the commercial (OptiForm) SL/SD based formulations and stored for 30
      days at 4 degrees C. When cold-smoked salmon slices and fillets were stored at 4
      degrees C, alginate coatings supplemented with 2.4%SL/0.25%SD and the commercial
      product OptiForm significantly delayed the growth of L. monocytogenes during the
      30-day storage with final counts reaching 4.1 and 3.3 log CFU/g (slices) and 4.4
      and 3.8 log CFU/g (fillets), respectively, while the counts in their untreated
      counterparts were significantly higher (P<0.05) reaching 7.3 and 6.8 log CFU/g
      for slices and fillets, respectively. Therefore, this study demonstrates the
      effectiveness of using an alginate-based coating containing lactate and diacetate
      to control the growth of L. monocytogenes to enhance the microbiological safety
      of filleted and sliced smoked salmon.

PMID- 19861231
TI  - Cytoplasmatic domain of Na,K-ATPase alpha-subunit is responsible for the
      aggregation of the enzyme in proteoliposomes.
AB  - We studied the thermal dependence of amide I' infrared absorption and
      fluorescence emission of Trp residues in the Na,K-ATPase of rabbit kidney. We
      studied the whole enzyme solubilized with detergent, the whole enzyme
      reconstituted in proteoliposomes and the protein fraction that remained in the
      lipid membrane after the trypsin digestion of the proteoliposomes. Cooperative
      unfolding and aggregation with increasing temperature were observed in the whole
      protein, whether solubilized or reconstituted, but not in the fraction remaining
      after trypsinization. The protein influenced the physical state of the lipid,
      decreasing the temperature of the gel to liquid-crystalline phase transition and
      the degree of cooperativity. This study provides new information for the
      understanding of the processes controlling the association mechanisms that are
      important for enzyme function in natural membranes.

PMID- 19861232
TI  - High-light induced singlet oxygen formation in cytochrome b(6)f complex from
      Bryopsis corticulans as detected by EPR spectroscopy.
AB  - Electron paramagnetic resonance (EPR) spectroscopy was used to detect the light
      induced formation of singlet oxygen ((1)O(2)*) in the intact and the Rieske
      depleted cytochrome b(6)f complexes (Cyt b(6)f) from Bryopsis corticulans, as
      well as in the isolated Rieske Fe-S protein. It is shown that, under white-light
      illumination and aerobic conditions, chlorophyll a (Chl a) bound in the intact
      Cyt b(6)f can be bleached by light-induced (1)O(2)*, and that the (1)O(2)*
      production can be promoted by D(2)O or scavenged by extraneous antioxidants such
      as l-histidine, ascorbate, beta-carotene and glutathione. Under similar
      experimental conditions, (1)O(2)* was also detected in the Rieske-depleted Cyt
      b(6)f complex, but not in the isolated Rieske Fe-S protein. The results prove
      that Chl a cofactor, rather than Rieske Fe-S protein, is the specific site of
      (1)O(2)* formation, a conclusion which draws further support from the generation
      of (1)O(2)* with selective excitation of Chl a using monocolor red light.

PMID- 19861233
TI  - Autism meets schizophrenia via cadherin pathway.

PMID- 19861235
TI  - A multi-criteria assessment of scenarios on thermal processing of infectious
      hospital wastes: a case study for Central Macedonia.
AB  - In Greece more than 14,000 tonnes of infectious hospital waste are produced
      yearly; a significant part of it is still mismanaged. Only one off-site licensed
      incineration facility for hospital wastes is in operation, with the remaining of
      the market covered by various hydroclave and autoclave units, whereas numerous
      problems are still generally encountered regarding waste segregation, collection,
      transportation and management, as well as often excessive entailed costs.
      Everyday practices still include dumping the majority of solid hospital waste
      into household disposal sites and landfills after sterilization, still largely
      without any preceding recycling and separation steps. Discussed in the present
      paper are the implemented and future treatment practices of infectious hospital
      wastes in Central Macedonia; produced quantities are reviewed, actual treatment
      costs are addressed critically, whereas the overall situation in Greece is
      discussed. Moreover, thermal treatment processes that could be applied for the
      treatment of infectious hospital wastes in the region are assessed via the multi
      criteria decision method Analytic Hierarchy Process. Furthermore, a sensitivity
      analysis was performed and the analysis demonstrated that a centralized autoclave
      or hydroclave plant near Thessaloniki is the best performing option, depending
      however on the selection and weighing of criteria of the multi-criteria process.
      Moreover the study found that a common treatment option for the treatment of all
      infectious hospital wastes produced in the Region of Central Macedonia, could
      offer cost and environmental benefits. In general the multi-criteria decision
      method, as well as the conclusions and remarks of this study can be used as a
      basis for future planning and anticipation of the needs for investments in the
      area of medical waste management.

PMID- 19861236
TI  - Arthroscopic anterior cruciate ligament surgery: results of autogenous patellar
      tendon graft versus the Leeds-Keio synthetic graft five year follow-up of a
      prospective randomised controlled trial.
AB  - We conducted a prospective, randomised controlled trial comparing anterior
      cruciate ligament reconstruction using middle third patellar tendon graft (PT) to
      synthetic Leeds-Keio (LK) ligament. The patients were randomised (26 PT, 24 LK).
      Subjective knee function was classified (Lysholm, Tegner activity, IKDC scores),
      laxity was measured (Lachman test, Stryker laxometer), and functional ability was
      assessed (one-hop test). There were no significant differences between Lysholm or
      IKDC scores at any stage by 5 years. Significant differences were found between
      the groups at 2 years for Tegner activity scores, laxity and one-hop testing. By
      5 years there were no significant differences. Clinical equivalence was
      demonstrated between the two groups for the Lysholm score and one-hop test but
      not for the Tegner activity score at 5 years. The use of the LK ligament has been
      largely abandoned due to reports of its insufficiency. Our results demonstrate
      that it is not as inferior as one might expect. We conclude that the results of
      LK ligament ACL reconstruction are as acceptable as those using PT. It may
      provide an additional means of reconstruction where no suitable alternative is
      present.

PMID- 19861234
TI  - Language network dysfunction as a predictor of outcome in youth at clinical high
      risk for psychosis.
AB  - OBJECTIVES: Language processing abnormalities are a hallmark feature of
      schizophrenia. Yet, no study to date has investigated underlying neural networks
      associated with discourse processing in adolescents at clinical high risk (CHR)
      for developing psychosis(1). METHODS: Forty CHR youth and 24 demographically
      comparable healthy controls underwent functional magnetic resonance imaging while
      performing a naturalistic discourse processing paradigm. We assessed differences
      in blood oxygenation level-dependent (BOLD) activity between task conditions
      (Topic Maintenance vs. Reasoning) and between groups. Furthermore, we examined
      the association of regional brain activity with symptom severity and social
      outcome at follow-up, 6 to 24 months after the scan. RESULTS: Relative to
      controls, CHR participants showed increased neural activity in a network of
      language-associated brain regions, including the medial prefrontal cortex
      bilaterally, left inferior frontal (LIFG; BA44/45, 47) and middle temporal gyri,
      and the anterior cingulate (BA24 and 32). Further, increased activity in the
      superior temporal gyrus (STG), caudate, and LIFG distinguished those who
      subsequently developed psychosis. Within the CHR sample, severity of positive
      formal thought disorder at follow-up was positively correlated with signal change
      in the LIFG, superior frontal gyrus, and inferior/middle temporal gyri, whereas
      social outcome was inversely correlated with signal change in the LIFG and
      anterior cingulate. CONCLUSIONS: These findings are consistent with a neural
      inefficiency hypothesis in those at greatest risk for psychosis, and additionally
      suggest that baseline activation differences may predict symptomatic and
      functional outcome. These results highlight the need to further investigate the
      neural systems involved in conversion to psychosis, and how language disruption
      changes over time in at-risk adolescents.

PMID- 19861237
TI  - Development and characterization of lysine based tripeptide analogues as
      inhibitors of Sir2 activity.
AB  - Sirtuins are NAD(+) dependent deacetylases that modulate various essential
      cellular functions. Development of peptide based inhibitors of Sir2s would prove
      useful both as pharmaceutical agents and as effectors by which downstream
      cellular alterations can be monitored. Click chemistry that utilizes Huisgen's
      1,3-dipolar cycloaddition permits attachment of novel modifications onto the side
      chain of lysine. Herein, we report the synthesis of peptide analogues prepared
      using click reactions on Nepsilon-propargyloxycarbonyl protected lysine residues
      and their characterization as inhibitors of Plasmodiumfalciparum Sir2 activity.
      The peptide based inhibitors exhibited parabolic competitive inhibition with
      respect to acetylated-peptide substrate and parabolic non-competitive inhibition
      with NAD(+) supporting the formation of EI(2) and E.NAD(+).I(2) complexes. Cross
      competition inhibition analysis with the non-competitive inhibitor nicotinamide
      (NAM) ruled out the possibility of the NAM-binding site being the second
      inhibitor binding site, suggesting the presence of a unique alternate pocket
      accommodating the inhibitor. One of these compounds was also found to be a potent
      inhibitor of the intraerythrocytic growth of P.falciparum with 50% inhibitory
      concentration in the micromolar range.

PMID- 19861238
TI  - Synthesis and biological evaluation of the metabolites of 2-(1-{3-[(6
      chloronaphthalen-2-yl)sulfonyl]propanoyl}piperidin-4-yl)-5-methyl-1,2-dihydro-3H
      imidazo[1,5-c]imidazol-3-one.
AB  - We have recently discovered imidazo[1,5-c]imidazol-3-one derivative 1 as a
      potent, selective, and orally bioavailable factor Xa (FXa) inhibitor. In this
      study, we have synthesized metabolites of 1 and evaluated their biological
      activities. As a result, we identified the active metabolites S-5 and 6 with a
      potent FXa inhibitory activity comparable to 1 and a favorable pharmacokinetic
      profile in monkeys.

PMID- 19861240
TI  - [Construction of a bait plasmid containing HBV PreS1 gene in a yeast two-hybrid
      system and evaluation of its toxicity and self-activation].
AB  - OBJECTIVE: To construct a yeast expression vector of hepatitis B virus (HBV)
      PreS1 gene using the Sos-recruitment system (SRS), and evaluate the effect of the
      expression product on the growth of the yeast cells and activation of the
      reporter gene. METHODS: The coding sequence of HBV preS1 was amplified by PCR and
      cloned into the yeast expression plasmid pSos. The recombinant bait plasmid pSos-
      PreS1 was verified by sequencing before transformation into competent yeast
      cells. The effects of the expression product on the yeast cell growth and
      activation of the reporter gene were evaluated. RESULTS: The yeast expression
      vector of HBV PreS1 gene was constructed successfully. The recombinant bait
      plasmid showed no toxic effect on yeast cdc25H cells without a self-activation of
      the reporter gene. CONCLUSION: The SRS can be used to study the proteins
      interacting with HBV PreS1 protein and provides a means for obtaining insight
      into the pathogenic mechanism of HBV.

PMID- 19861239
TI  - cJun modulates Ggamma-globin gene expression via an upstream cAMP response
      element.
AB  - The upstream Ggamma-globin gene cAMP response element (G-CRE) was previously
      shown to play a role in drug-mediated fetal hemoglobin induction. This effect is
      achieved via p38 mitogen activated protein kinase (MAPK)-dependent CREB1 and ATF
      2 phosphorylation and G-CRE transactivation. Since this motif is also a predicted
      consensus binding site for cJun we extended our analysis to determine the ability
      of cJun to transactivate gamma-globin through the G-CRE. Using chromatin
      immunoprecipitation assays we showed comparable in vivo cJun and CREB1 binding to
      the G-CRE region. Protein-protein interactions were confirmed between cJun/ATF-2
      and CREB1/ATF-2 but not between CREB1 and cJun. However, we observed cJun and
      CREB1 binding to the G-CRE in vitro by electrophoretic mobility shift assay.
      Promoter pull-down assay followed by sequential western blot analysis confirmed
      co-localization of cJun, CREB1, and ATF-2 on the G-CRE. To show functional
      relevance, enforced expression studies with pLen-cJun and a Ggamma-promoter (
      1500 to +36) luciferase reporter were completed; we observed a concentration
      dependent increase in luciferase activity with pLen-cJun similar to that produced
      by CREB1 enforced expression. Moreover, the G/A mutation at -1225 in the G-CRE
      abolished cJun transactivation. Finally, enforced cJun expression in K562 cells
      and normal primary erythroid progenitors enhanced endogenous gamma-globin gene
      expression. We conclude that these data indicate that cJun activates the Ggamma
      globin promoter via the G-CRE in a manner comparable with CREB1 and propose a
      model for gamma-globin activation based on DNA-protein interactions in the G-CRE.

PMID- 19861241
TI  - [VIR576 inhibits antigen-specific T cell activation by binding to the
      transmembrane domain of T cell receptor].
AB  - OBJECTIVE: To study the mechanism underlying the inhibitory effect of the anti
      HIV peptide VIR576 on antigen-specific T cell activation. METHODS: CCK-8 assay
      was used to investigate the effect of VIR576 on the proliferation of splenocytes
      of OVA-specific DO11.10 Tg mice in response to chicken OVA. Hemolysis test,
      hemolysis inhibition assay and fluorescence binding assay were used to
      investigate the interaction of VIR576 with the transmembrane domain (TMD) of the
      T cell receptor (TCR). RESULTS: VIR576 inhibited HIV glycoprotein gp41 fusion
      peptide-mediated antigen specific T cell activation, and VIR576 itself also
      inhibited splenocyte proliferation in responses to OVA (P<0.05). Hemolysis test,
      hemolysis inhibition assay and fluorescence binding assay demonstrated that
      VIR576 suppressed TCR-TMD-mediated hemolysis and competitively inhibited Rho
      VIR576 binding to TCR-TMD peptide. CONCLUSION: VIR576 is effective in suppressing
      the antigen-specific T cell activation via TCR and can interact with TCR-TMD.
      VIR576 may serve as a potent microbicide candidate to block sexual transmission
      of HIV due to of its inhibitory effect on both HIV entry and antigen-specific T
      cell activation.

PMID- 19861242
TI  - [A comparative study of diffusion-weighted magnetic resonance imaging and
      pathological findings of liver fibrosis in rabbits].
AB  - OBJECTIVE: To investigate the alteration of apparent diffusion coefficient (ADC)
      in diffusion-weighted MR imaging (MR-DWI) of liver fibrosis and its pathological
      basis in rabbits. METHODS: Five rabbits in the control group and 22 with
      experimental liver fibrosis induced by transperitoneal injection of carbon
      tetrachloride (CCl4) were examined with MR-DWI. Diffusion-weighted SE EPI
      sequence with a relatively high b factor (b=600 s/mm2) was used to measure the
      ADC. The mean values of ADC were compared among the rabbits in different stages
      of liver fibrosis and analyzed in relation to the pathological findings. RESULTS:
      The mean ADC value decreased significantly with increased severity of liver
      fibrosis (P<0.05). Pathologically, the amount and extension of fibrotic matrix
      increased, and the hepatic necroinflammation worsened with the progression of the
      liver fibrosis. CONCLUSION: The ADC value decreases with the progression of liver
      fibrosis possibly as the result of water diffusion limitation due to increased
      fibrous tissue in the liver and abnormal water diffusion within the intracellular
      and extracellular spaces.

PMID- 19861243
TI  - [Effect of soluble total proteins of Zaocys dumnades on interleukin-1beta, tumor
      necrosis factor-alpha and interleukin-10 expressions in human fibroblast-like
      synoviocytes in vitro].
AB  - OBJECTIVE: To evaluate the effect of soluble total proteins of Zaocys dhumnades
      on the expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha
      (TNF-alpha) and IL-10 in human fibroblast-like synoviocytes (FLS) cultured in
      vitro. METHODS: Primary cultured FLS isolated from the synovium of patients with
      rheumatoid arthritis (RA) were incubated in the presence of different
      concentrations (50, 150 and 450 microg/ml) of soluble total proteins of Zaocys
      dhumnades, with Tripterygium hypoglaucum Hutch (THH) and DMEM as the positive and
      negative controls, respectively. Enzyme-linked immunosorbent assay (ELISA) and RT
      PCR were used to detect the expressions of IL-1beta, IL-10 and TNF-alpha in the
      FLS. RESULTS: The protein and mRNA levels of IL-1beta and TNF-alpha in the
      supernatant of the FLS exposed to 150 and 450 microg/ml of the soluble total
      proteins of Zaocys dhumnades decreased, while IL-10 protein and mRNA increased
      significantly as compared with those in the negative control group (P<0.01).
      CONCLUSION: The soluble total proteins of Zaocys dhumnades produce therapeutic
      effect on RA possibly by inhibiting IL-1beta and TNF-alpha and promoting IL-10
      expressions in the FLS.

PMID- 19861244
TI  - [Analysis of the genetic polymorphism of 17 Y-chromosomal short tandem repeat
      loci in the Han population in Chengdu].
AB  - OBJECTIVE: To obtain the population genetic data of 17 Y-chromosomal short tandem
      repeat (Y-STR) in the Han population in Chengdu of Sichuan Province. METHODS: The
      17 Y-STR loci were amplified from the blood samples of 111 unrelated Chengdu Han
      individuals using the AmpFlSTR Yfiler system. The PCR products were genotyped
      with an ABI 3130 genetic analyzer. RESULTS: In the loci of in DYS456, DYS389I,
      DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635,
      DYS392, Y-GATA-H4, DYS437, DYS438, and DYS448, 3 to 8 alleles were detected in
      the Han population in Chengdu, and 36 alleles were detected in the locus
      DYS385a/b, with the minimal gene diversity (GD) value of 0.3970 (DYS391) and
      maximal value of 0.9561 (DYS385a/b). The DNA samples of 16 women and 7 different
      species of animals were amplified, but no specific products were found for the 17
      Y-STR loci. No mutations of the 17 Y-STR alleles were observed in 20 father-son
      pairs as confirmed by autosomal STR analysis. CONCLUSION: The 17 Y-STR loci are
      highly polymorphic and are suitable for personal identification, paternity
      testing, population genetics and anthropology studies.

PMID- 19861245
TI  - [Reactive oxygen species scavenger protects cardiac cells against injuries
      induced by chemical hypoxia].
AB  - OBJECTIVE: To investigate the protective effect of reactive oxygen species (ROS)
      scavenger, N-acetyl-L-cysteine (NAC), against H9c2 cardiomyocytes from injuries
      induced by chemical hypoxia. METHODS: H9c2 cells were treated with cobalt
      chloride (CoCl2), a chemical hypoxia-mimetic agent, to establish the chemical
      hypoxia-induced cardiomyocyte injury model. NAC was added into the cell medium 60
      min prior to CoCl2 exposure. The cell viability was evaluated using cell counter
      kit (CCK-8), and the intercellular ROS level was measured by 2', 7'-
      dichlorfluorescein-diacetate (DCFH-DA) staining and photofluorography.
      Mitochondrial membrane potential (MMP) of the cells was observed by Rhodamine123
      (Rh123) staining and photofluorography, and the ratio of GSSG/ (GSSG+GSH) was
      calculated according to detection results of the GSSG kit. RESULTS: Exposure of
      H9c2 cardiomyocytes to 600 micromol/L CoCl2 for 36 h resulted in significantly
      reduced cell viability. Pretreatment with NAC at the concentrations ranging from
      500 to 2000 micromol/L 60 min before CoCl2 exposure dose-dependently inhibited
      CoCl2-induced H9c2 cell injuries, and obviously increased the cell viability. NAC
      at 2000 micromol/L obviously inhibited the oxidative stress induced by CoCl2,
      decreased the ratio of GSSG/(GSSG+GSH), increased ROS level, and antagonized
      CoCl2-induced inhibition on MMP. CONCLUSION: NAC offers obvious protective effect
      on H9c2 cardiomyocytes against injuries induced by chemical hypoxia by decreasing
      in the ratio of GSSG/(GSSG+GSH) and ROS level and ameliorating MMP.

PMID- 19861247
TI  - [Follicular cell implantation for induce hair follicle growth in nude mice].
AB  - OBJECTIVE: To establish a convenient and reliable method for inducing hair
      regeneration by follicular cell implantation for the treatment of alopecia.
      METHODS: The human hair follicle stem cells were separated and purified by
      micromanipulation and magnetic cell sorting, and human scalp dermal papilla cells
      were isolated by enzyme digestion. The two cells were mixed and implanted
      subcutaneously in nude mice to observe the regeneration of the hair follicles.
      RESULTS: Formation of intact hair follicle-like structures was observed in the
      skin sections of the recipient nude mice. CONCLUSION: Follicular cell
      implantation can induce hair follicle-like structures in nude mice, which
      provides a means for efficient hair regeneration for treatment of hair loss.

PMID- 19861246
TI  - [Denaturing high-performance liquid chromatography for screening antithrombin III
      gene mutation and polymorphisms in patients with cerebral venous thrombosis].
AB  - OBJECTIVE: To identify antithrombin III (AT-III) gene mutation and polymorphisms
      in pregnant women and parturients with cerebral venous thrombosis (CVT) using
      denaturing high-performance liquid chromatography (DHPLC). METHODS: The genomic
      DNA was extracted from the blood samples of 50 pregnant women and parturients
      with CVT and 52 matched healthy women for molecular analysis using a PCR/DHPLC
      assay followed by DNA sequence analysis. Ten primer pairs were designed for
      amplifying the AT- III promoter region and exons 1-6 including the exon/intron
      boundaries. A rapid screening assay based on DHPLC was established to screen the
      mutation and polymorphisms of AT- III gene. RESULTS: Six abnormal peaks were
      detected in 40 of the patients by DHPLC. Direct DNA sequencing was performed on
      representative samples detected by DHPLC profiling. One pathogenic heterozygous
      G13328A missense mutation in exon 6, and a novel silent mutation in exon 4+243
      G>A were identified. Six single nucleotide polymorphism (SNP) sites were found,
      including 4 previously reported ones in the SNP library and two were novel SNP
      sites. An abnormal peak was detected in the control group by DHPLC. CONCLUSION:
      DHPLC allows automated and rapid high-throughput detection of AT- III gene
      mutation and polymorphisms in the clinical setting and prenatal diagnosis. Our
      findings suggested that AT- III gene mutation, as well as its polymorphisms,
      contributes to the occurrence of CVT in pregnant women and parturients.

PMID- 19861248
TI  - [Small interfering RNA-mediated COX-2 gene silencing inhibits the proliferation
      and migration of human ovarian cancer cell line CAOV-3].
AB  - OBJECTIVE: To investigate the changes in the proliferation and migration of human
      ovarian cancer cells (CAOV-3) after knocking down COX-2 gene by RNA interference.
      METHODS: The recombinant plasmid of pGenesil-1-siRNA-COX-2 was constructed and
      transfected into CAOV-3 cells. The transcription of COX-2 gene was detected by
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and
      the protein expression of COX-2 was determined by Western blotting . MTT assay
      was used to investigate the proliferation of the transfected CAOV-3 cells, and
      the cell migration was evaluated using a transwell migration assay. RESULTS: COX
      2 mRNA and protein levels were significantly reduced after pGenesil-1-siRNA-COX-2
      transfection into CAOV-3 cells, which showed obvious reduction in the cell
      proliferation and migration. CONCLUSION: RNA interference allows obvious COX-2
      gene knocking down in human ovarian cancer cells to result in lowered cell growth
      rate and migration ability. COX-2 gene may become a new therapeutic target for
      ovarian cancer.

PMID- 19861249
TI  - [Role of interleukin 17 in viral myocarditis and dilated cardiomyopathy].
AB  - OBJECTIVE: To explore the role of interleukin-17 (IL-17) in the evolution of
      viral myocarditis (VMC) into dilated cardiomyopathy (DCM). METHODS: A mouse model
      of VMC was established in 100 male Balb/c mice by intraperitoneal injection of
      coxsackievirus B3. The expression of IL-17 protein in the cardiac tissue of the
      mice was detected immunohistochemically, and IL-17 mRNA in the splenocytes was
      examined by reverse transcription-polymerase chain reaction (RT-PCR). IL-17
      levels in the plasma, peripheral blood mononuclear cell (PBMC) culture
      supernatants, and phytohemagglutinin (PHA)-stimulated PBMC culture supernatants
      were measured in 30 DCM patients, 26 non-DCM patients and 20 normal adults using
      enzyme-linked immunosorbent assay (ELISA), and IL-17 mRNA expression in the PBMCs
      was detected using RT-PCR. RESULTS: The levels of IL-17 mRNA in the splenocytes
      of the mice with VMC were significantly higher at 4 and 6 weeks than those at 8
      weeks (P<0.01), but not detected at 2 weeks. No IL-17 expression was found in the
      ventricular tissue of the mice at 2 weeks, but peaked at 4 weeks followed by
      gradual decrease (P<0.01). IL-17 level in PHA-stimulated PBMC culture
      supernatants but not the plasma, and its mRNA level in PHA-stimulated PBMCs but
      not the PBMC culture supernatants, were significantly elevated in DCM patients as
      compared with those in non-DCM patients and normal control subjects. CONCLUSIONS:
      The mouse model of VMC in the chronic phase and DCM patients express high levels
      of IL-17, which may contribute to the transition from VMC to DCM.

PMID- 19861250
TI  - [Effects of small interfering RNA targeting connective tissue growth factor on
      high glucose-induced human tubular epithelial hypertrophy].
AB  - OBJECTIVE: To observe the effect of transfection with small interfering RNA
      (siRNA) targeting connective tissue growth factor (CTGF) on human tubular
      epithelial hypertrophy induced by high glucose. METHODS: HK-2 cells were cultured
      in DMEM/F12 medium containing 1 g/L glucose (normal control group), 4.5 g/L
      glucose (high glucose group), or 1 g/L glucose+3.5 g/L mannitol (iso-osmolar
      control group). The cells were transfected with pGenesil-1, pGenesil/neg, or
      pGenesil/siRNA-CTGF and then cultured in DMEM/F12 medium containing 4.5 g/L
      glucose as the high glucose+blank control group, high glucose+negative control
      group and high glucose+interference group, respectively. After cell culture for
      24, 48 and 96 h, the cells were collected to detect the mRNA and protein levels
      of CTGF by real-time PCR and Western blotting, respectively. The proliferative
      activities of the cells were evaluated with MTT assay, and the total cellular
      protein contents were determined with Bradford method. Flow cytometry was
      employed to analyzed the cell cycle changes. RESULTS: High-glucose significantly
      up-regulated the CTGF mRNA and protein levels in HK-2 cells. The cell
      proliferation was inhibited after high-glucose exposure with increased cell
      percentage in G1 phase and total cellular protein content suggesting cellular
      hypertrophy. Transfection with siRNA targeting CTGF significantly inhibited high
      glucose-induced up-regulation of CTGF mRNA and protein and promoted the cell
      proliferation, resulting also increased cells in S phase and lowered total
      cellular protein contents. CONCLUSION: CTGF is an important mediator of high
      glucose-induced tubular epithelial hypertrophy, and transfection with siRNA
      targeting CTGF can alleviate the hypertrophy, suggesting the potential value of
      CTGF-targeted treatment in the management of diabetic nephropathy.

PMID- 19861251
TI  - [Value of color Doppler ultrasonography, contrast-enhanced ultrasound and serum
      CA-125 detection in differential diagnosis of ovarian masses].
AB  - OBJECTIVE: To assess the value of color Doppler ultrasonography, contrast
      enhanced ultrasound and detection of serum CA-125 levels in the differential
      diagnosis of ovarian masses. METHODS: The findings of color Doppler
      ultrasonography, contrast-enhanced ultrasound and the serum levels of CA-125 were
      comparatively analyzed in 65 patients with ovarian masses, and the diagnostic
      accuracy of the 3 methods was estimated. RESULTS: Of the 65 cases of ovarian
      masses, 21 of the 35 patients with benign ovarian masses had serum CA-125 levels
      below 35 U/ml , and 28 of the 30 patients with malignant masses showed CA-125
      levels over 35 U/ml. Color Doppler ultrasonography identified 30 benign and 22
      malignant cases, but failed to produce definite results in 13 cases (including 5
      with benign and 8 with malignant masses). By contrast-enhanced ultrasound, benign
      masses were found in 34 cases and malignant masses in 29 cases, and misdiagnosis
      occurred in 2 cases (including 1 case of thecoma and 1 of ovarian borderline
      tumor). With serum CA-125 detection, color Doppler ultrasonography and contrast
      enhanced ultrasound, the diagnostic sensitivity for ovarian masses was 66.7%,
      73.3%, and 96.7%, and the specificity was 60.0%, 85.7%, and 97.1%, respectively.
      CONCLUSIONS: Detection of serum CA-125 level and ultrasound examinations help in
      the diagnosis and differential diagnosis of benign and malignant ovarian masses.
      Compared with serum CA-125 detection and color Doppler ultrasonography, contrast
      enhanced ultrasound is more informative on perfusion patterns of the ovarian
      masses to result in higher accuracy in early and differential diagnosis of the
      ovarian masses.

PMID- 19861252
TI  - [P38MAPK pathway regulates COX-2 and caspase-3 expression in a mouse model of
      Parkinson disease].
AB  - OBJECTIVE: To investigate the effect of p38 mitogen-activated protein kinase
      (p38MAPK) on the expression of COX-2 and caspase-3 in the substania nigra (SN) of
      mice with MPTP-induced Parkinson disease (PD). METHODS: C57BL/CN mice were
      treated with MPTP to prepare a subacute PD model, and their behavioral changes
      following the treatment were observed. Immunohistochemistry and Western blotting
      were performed to detect the expression of tyrosine hydroxylase (TH), COX-2 and
      phosphorylation of P38MAPK in the SN and their changes following treatment with
      SB203580, a specific inhibitor of P38MAPK. RESULTS: The 7-day model group showed
      typical symptoms of PD with decrements of TH-positive neurons and TH protein
      level in the SN of the midbrain by about 65% and 75%, respectively (P<0.01). In
      the 3-day model group, the COX-2-, caspase-3- and phosphorylated P38MAPK
      immunoreactive cells and their protein levels in the SN increased markedly with
      obvious loss of TH-positive neurons. Administration of SB203580 obviously
      lessened the above changes (P<0.01). CONCLUSION: P38MAPK regulates the
      inflammation and apoptosis in the SN of the mouse model of subacute PD, and
      SB203580 may provide some neuroprotective effect.

PMID- 19861253
TI  - [Effect of ultra-early hyperbaric oxygenation on spinal edema and hind limb motor
      function in rats with complete spinal cord transection].
AB  - OBJECTIVE: To evaluate the effect of ultra-early hyperbaric oxygenation on spinal
      edema and hind limb motor function in rats with complete spinal cord transection.
      METHODS: Fifty-five healthy 3-month-old female SD rats were randomly divided into
      sham-operated group (n=15), complete spinal cord transection group (CSCT group,
      n=20) and hyperbaric oxygen group (HBO group, n=20). The rats in the sham
      operated group underwent only laminectomy, while those in the other 2 groups
      underwent CSCT at the T10 level. The rats in HBO group were placed in an oxygen
      chamber 3 h after the operation for 10 days as a treatment course, and 3
      treatment courses were administered at the interval of 6 days. In the first
      treatment course, 2 hyperbaric oxygenation sessions were given daily, and in the
      following 2 course, only 1 session was given daily. The recovery of hindlimb
      motor function was evaluated using the open-field Basso-Beattie-Bresnahan (BBB)
      scoring system once a week for 6 weeks. All the rats were sacrificed 6 weeks
      after the operation to measure the water content in the injured tissues. RESULTS:
      The BBB scores of CSCT group and HBO group gradually increased with the passage
      of time after the operation, and from week 2 to week 6, HBO group had
      significantly higher scores than CSCT group (P<0.05). The water content was
      markedly increased in CSCT group at 6 weeks after the operation as compared with
      that in the sham-operated group (P<0.01), and significantly reduced in HBO group
      in comparison with that in the CSCT group (P<0.05). CONCLUSION: Ultra-early HBO
      can suppress spinal cord edema and promote hindlimb locomotor recovery in rats
      with complete spinal cord transection.

PMID- 19861254
TI  - [Correlation between increased spinal cord signal intensity on T2-weighted MRI
      and clinical prognosis of compressive cervical myelopathy].
AB  - OBJECTIVE: To analyze the correlations between increased spinal cord signal
      intensity on magnetic resonance images (MRI) and the clinical prognosis of
      compressive cervical myelopathy. METHODS: Sixty-six patients with cervical
      spondylotic myelopathy underwent surgeries through the anterior approach. In all
      the patients, the diagnoses were established on the basis of both neurological
      examination and MRI findings that showed spinal cord compression. The patients
      were divided into two groups according to preoperative MRI, namely isointense MRI
      T1/T2 signal group and iso/hyperintense MRI T1/T2 group. The JOA scores of the
      patients were evaluated before and at 6 and 12 months after the operation.
      RESULTS: The patients were followed up for 12 to 38 months after the operation
      (mean 21 months), and no statistically significant difference were found in the
      pre- and postoperative JOA scores between the two groups (P>0.05). CONCLUSION:
      The peoperative hyperintense signals on T2 weighted MRI does not correlate to the
      prognosis of patients with compressive cervical myelopathy, who may also have
      favorable clinical outcomes after the operation.

PMID- 19861255
TI  - [CORBA-based design and packaging of picture archiving and communication system
      object].
AB  - Regionalization has become one of the most important trends in the development of
      picture archiving and communication systems (PACS) due to the existence of large
      amounts of information islands. The conventional PACS designed according to the
      DICOM standard on the basis of the C/S structure fails to meet the demand of
      regional information system maintenance. A regional PACS system based on common
      object request broker architecture (CORBA) distributed technology is therefore
      proposed and implemented. This article describes the design and packaging of the
      PACS objects. When mounting a series of separate logical and related functional
      PACS objects on the ORB bus, the multi-scale PACS systems can be established.
      This method eliminates the limitation of the C/S structure and offers good
      compatibility and scalability.

PMID- 19861256
TI  - [Subcutaneous implantation of embryonic skin cells to construct a model of hair
      development in nude mice].
AB  - OBJECTIVE: To observe the hair development after subcutaneous implantation of
      embryonic skin cells in nude mice, and construct a model of hair development.
      METHODS: Dermal and epidermal cells isolated from embryonic mouse skin were mixed
      at a given ratio and injected subcutaneously in nude mice, and hair formation
      after the implantation was observed under a microscope. RESULTS: Formation of the
      hair follicles and fibers under the skin of the recipient nude mice and emergence
      of the hair shaft were observed microscopically. CONCLUSION: Embryonic skin cells
      be used to construct a complete model of hair development after implantation in
      vivo.

PMID- 19861257
TI  - [Effect of levosimendan on B-type natriuretic peptide levels in patients with
      advanced heart failure: a meta-analysis].
AB  - OBJECTIVE: To conduct a meta-analysis of the effect of levosimendan on B-type
      natriuretic peptide (BNP) levels and evaluate the therapeutic effect of
      levosimendan on advanced heart failure. METHODS: A meta-analysis was performed on
      the selected data to analyze the effect of levosimendan on BNP levels. RESULTS:
      Levosimendan decreased BNP by a mean of 337.66 [95%CI (-296.30, -379.02)] pg/ml
      24 h after the administration, and by 259.92 [95%CI (-195.76, -324.08)] pg/ml at
      48 h, and by 123.09 [95%CI(-53.32,-195.86)] pg/ml at 1 week. Levosimendan
      resulted in improvements of the cardiac function by about 29%, 22%, and 10% at 24
      h, 48 h and 1 week after the administration. CONCLUSION: Levosimendan produces
      favorable effects on the cardiac functions and BNP levels.

PMID- 19861258
TI  - [Changes of systemic and pulmonary hemodynamics and plasma levels of inducible
      nitric oxide synthase and endothelin-1 in patients with hepatopulmonary
      syndrome].
AB  - OBJECTIVE: To observe the changes of systemic and pulmonary hemodynamics and the
      plasma levels of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1)
      and investigate their association in patients with hepatopulmonary syndrome
      (HPS). METHODS: Twenty-six patients with HPS undergoing orthotopic liver
      transplantation (OLT) were enrolled in this study with 20 patients without
      hypoxemia as the control group. Blood samples were taken one day before OLT to
      measure the plasma levels of iNOS and ET-1 using fluorescence quantitative
      polymerase chain reaction (FQ-PCR) and radioimmunoassay, respectively, with 10
      healthy volunteers serving as the healthy control group. Before the operation for
      OLT, the parameters of systemic and pulmonary hemodynamics were monitored after
      anesthesia induction. RESULTS: The systemic and pulmonary hemodynamics in
      patients without hypoxemia was characterized by high cardiac output and low
      resistance, and by comparison, the patients with HPS showed even higher cardiac
      output and lower mean pulmonary artery pressure, pulmonary artery wedge pressure,
      systemic vascular resistance and pulmonary vascular resistance. The two patient
      groups had comparable plasma iNOS and ET-1 levels, which were both higher than
      those in the healthy control group. CONCLUSION: The hemodynamics in patients with
      end-stage liver disease exhibit a pattern of high cardiac output and low
      resistance, which is more obvious in HPS patients possibly in association with
      elevated plasma levels of iNOS and ET-1.

PMID- 19861259
TI  - [Inactivation of bacterial spores using low-temperature plasma].
AB  - OBJECTIVE: To investigate the effect of low-temperature plasma on inactivation of
      bacterial spores and explore the mechanism. METHODS: Dielectric barrier discharge
      (DBD) was employed to generate the atmospheric low-temperature plasma for
      treatment of B.subtilis var. niger spores with the gas spacing of 3, 4 and 5 and
      treatment time intervals of 5, 10, 15, 20, 25, 30 and 35 s. The survived colonies
      was counted with plate counting method, and the killing log value (KLV) at
      different treatment times was calculated. The inactivation effect of electric
      field on B.subtilis var.niger spores was also investigated and the spores treated
      with low-temperature plasma were observed with transmission electron microscope.
      RESULTS: With the gap spacing of 3, 4 and 5 mm, the KLV of low-temperature plasma
      on B.subtilis var.niger spores within 25, 30 and 35 s of exposure was more than
      5. The germicidal effects of the electric field on B. subtilis var.niger spores
      were rather poor. Transmission electron microscopy demonstrated total destruction
      of the surface and interior structure of the spores by low-temperature plasma.
      CONCLUSIONS: Low-temperature plasma is effective for inactivation of the
      bacterial spores with a time and dose dependence. The penetrating effect of
      charged particles and oxygenation effect of the reactive oxygen species might
      play a dominant role in plasma-induced bacterial spore inactivation, while the
      role of electric field is negligible.

PMID- 19861260
TI  - [Phylogenetic analysis and PCR-restriction fragment length polymophism
      identification of Salmonella based on grOEL gene sequence].
AB  - OBJECTIVE: To investigate the value of grOEL gene sequence in phylogenetic
      analysis and typing of Salmonella. METHODS: The grOEL gene was amplified by PCR,
      sequenced and analyzed using Bioedit and DNAstar software. The Salmonella strains
      were identified using PCR-restriction fragment length polymophism (PCR-RFLP).
      RESULTS: The conservative and variable regions of grOEL gene of Salmonella
      serogroup were separately distributed and most of the small mutant regions
      distributed intermittently among the conservative regions. The phylogenetic tree
      of Salmonella based on the nucleotides differed from that generated based on the
      amino acid sequence. O8, O9 and O10 had the closest consanguinity, and 5 patterns
      were identified by PCR-RFLP. CONCLUSION: The grOEL gene can be used as a genetic
      marker for phylogenetic analysis of Salmonella and also as a target sequence for
      Salmonella typing identification.

PMID- 19861261
TI  - [Small interfering RNA-mediated islet neogenesis associated protein gene
      silencing inhibits the proliferation of INS-1 islet cells].
AB  - OBJECTIVE: To investigate the effect of small interfering RNA (siRNA)-mediated
      islet neogenesis associated protein (INGAP) gene silencing on the proliferation
      of islet cells. METHODS: Different siRNAs targeting INGAP gene were designed and
      transfected into INS-1 islet cells, and the expression levels of INGAP mRNA and
      protein following the transfection were detected using RT-PCR, flow cytometry and
      Western blotting. The proliferation of the transfected INS-1 cells was evaluated
      using MTT assay. RESULTS: Compared with those in the irrelevant siRNA, empty
      vector control, and un-transfected groups, the expression levels of INGAP mRNA
      and protein in the cells transfected with siRNA6 were reduced significantly. The
      cell proliferation rate significantly increased after transfection with siRNA6
      (P<0.05). CONCLUSION: siRNA targeting INGAP can effectively down-regulate INGAP
      expression and inhibit the proliferation of INS-1 cells.

PMID- 19861262
TI  - [Inhibitory effect of a HBV vector plasmid expressing A3C on HBV replication].
AB  - OBJECTIVE: To observe the inhibitory effect of a replication-defective hepatitis
      B virus (HBV) vector plasmid expressing A3C on HBV replication in vitro. METHODS:
      The HBV vector plasmisd pCH-LJ3-A3C and pCH-LJ3-hrGFP expressing A3C and hrGFP
      were constructed using PCR and gene recombination technique. The two recombinant
      plasmids were separately cotranfected into HepG2 cells along with the wild-type
      HBV plasmid pCH-3093. The HBV DNA in the cell cytoplasmic lysates and in the cell
      culture supernatant was extracted for Southern blotting, and the nucleocapsid
      associated HBV DNA were amplified by PCR, cloned and sequenced. RESULTS: pCH-LJ3
      A3C showed obvious inhibitory effect on HBV DNA in the cytoplasmic lysates and
      cell culture supernatant, causing a reduction of the HBV DNA by 31% and 40%,
      respectively. The pCH-LJ3-A3C plasmid was capable of editing the HBV DNA. Among
      the 50 sequenced clones, 36 clones had G-A mutations, with a total of 982 such
      mutations. CONCLUSION: pCH-LJ3-A3C can inhibit the replication of HBV primarily
      by editing HBV DNA. The pCH-LJ3-A3C plasmid may serve as a new antiviral agent
      against human HBV infection.

PMID- 19861263
TI  - [Effects of Panax notoginsenoside on TNF-alpha and MMP-2 expressions in rats with
      post-myocardial infarction ventricular remodeling and the mechanism].
AB  - OBJECTIVE: To observe the effects of Panax notoginsenoside (PNS) on tumor
      necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases-2 (MMP-2)
      expressions in rats with post-myocardial infarction ventricular remodeling and
      explore the mechanism. METHODS: Rat models of acute infarction ventricular (AMI)
      were established by ligation of the left anterior descending coronary artery.
      Twenty-four hours after the operation, the rats were randomized into control and
      experimental groups for intragastric administration of normal saline (control),
      fosinopril and PNS at the low, medium and high doses for 4 consecutive weeks. The
      effects of PNS on the cardiac function index including the left ventricular end
      diastolic dimension (LVIDd), left ventricular end-systolic diameter (LVIDs),
      ejection fraction (EF), percentage of left ventricular systole (FS), mitral early
      diastolic flow velocity mouth (MV), and heart rate (HR) were observed, and the
      changes in TNF-alpha and MMP-2 expression were detected after post-myocardial
      infarction ventricular remodeling. RESULTS: Compared with the control group, PNS
      at the medium and high doses produced significant improvements in the EF, FS and
      MV of the rats (P<0.01 or 0.05). TNF-alpha and MMP-2 expressions were
      significantly decreased by PNS treatment at low, medium and high doses (P<0.01).
      CONCLUSION: PNS can inhibit or reduce the expression of TNF-alpha and MMP-2,
      thereby enhancing left ventricular systolic and diastolic functions, decreasing
      peripheral resistance, and improving the cardiac function of rats with post
      myocardial infarction left ventricular remodeling.

PMID- 19861264
TI  - [Role of Toll-like receptor 2 in corneal graft rejection following penetrating
      keratoplasty].
AB  - OBJECTIVE: To gain insight into the role of Toll-like receptor 2 (TLR2) in graft
      rejection following penetrating keratoplasty, and investigate the expression of
      TLR2 mRNA in the corneal graft. METHODS: Penetrating keratoplasty was performed
      in 3 groups of rats for orthotopic autologous corneal transplantation (group A),
      allograft corneal transplantation (group B), or allograft corneal transplantation
      with hormone treatment (C). The transparency and neovascularization of the cornea
      were observed using a slit-lamp microscope and scored according to the rejection
      index, with normal cornea serving as the control. The corneal tissues were
      sampled at 5, 7, and 9 days after the transplantation for histopathological
      examination and detection of TLR2 mRNA expression using RT-PCR. RESULTS: With the
      passage of time, edema, opacities and neovascularization of the corneal graft
      occurred after the operation in all the groups. Seven days after the operation,
      the rejection index of group B, but not that of groups A and C, met the
      diagnostic criteria for graft rejection with also support by histopathological
      evidence. The expression of TLR2 mRNA was detected in normal corneas and
      augmented in the corneal grafts in the 3 transplantation groups. TLR2 mRNA
      expression in group B was significantly higher than that of group A, and the
      expression in group C decreased significantly in comparison with that in group B
      (P<0.05). CONCLUSION: As the recognition receptors of native immune system, TLR2
      in the rejected corneal grafts may recognize the allograft antigen and play a
      role in acute graft rejection after penetrating keratoplasty.

PMID- 19861265
TI  - [Impact of prosthesis-patient mismatch on the quality of life of elderly patients
      after aortic valve replacement].
AB  - OBJECTIVE: To evaluate the long-term changes in the quality of life (QOL) scores
      in elderly patients after aortic valve replacement, and assess the impact of
      prosthesis-patient mismatch on the QQL of the patients. METHODS: A prospective
      cohort study was conducted involving 100 consecutive elderly patients above 70
      years of age, who underwent isolated aortic valve or simultaneous aortic valve
      coronary artery bypass graft (CABG) procedures between August 10, 1995 and August
      19, 1998. Patient-prosthesis mismatch (PPM) was defined as a prosthetic aortic
      valve EOAI of 0.85 cm2/m2 or less. The clinical follow-up examinations were
      carried out at 4 weeks and 6 months after the operation, and then annually
      afterwards. Cumulative and comparative analyses of the long-term outcomes and
      gradient pressure of the prosthetic valve were performed. The QOL of the patients
      was evaluated using the Short Form 36-Item Health Survey (SF-36) questionnaire.
      RESULTS: The mean age of the patients at prosthesis implantation was 74.7-/+5.7
      years (range 70-87 years). The patients were followed up for a mean of 7.3-/+4.5
      years. The thirty-day mortality was 6.3% in the mismatch group, and 3.3% in the
      matching group. The freedom from death showed no significant difference between
      the two groups at the first, third and fifth years after the prosthetic
      implantation, but differed significantly at the seventh year. The
      echocardiographic data showed significant differences in the mean gradient
      pressure between the two groups at the first and fifth years postoperatively. At
      most of the time points for follow-up examination, the general health and
      energy/vitality of the patients all improved from the preoperative levels, but no
      significant improvement was found at the third, fifth, and seventh years in the
      role emotional, social role, or general mental health; at the first postoperative
      year, however, the role emotional, social role, and particularly mental health,
      presented with significant improvements in comparison with the preoperative
      levels. No obvious difference in the QOL was noted between the two groups at the
      time points of observation. CONCLUSIONS: Aortic vale replacement improves the QOL
      of the elderly patients, but the degree of improvements do not seem to be
      influenced by PPM. The interpretation of the impact of PPM on the clinic outcome
      of the patients still remains controversial.

PMID- 19861266
TI  - [Establishment and application of a loop-mediated isothermal amplification method
      for rapid diagnosis of Vibrio cholerae].
AB  - OBJECTIVE: To establish a loop-mediated isothermal amplification (LAMP) method
      for rapid diagnosis of Vibrio cholerae. METHODS: Based on the ompW nucleic
      sequence of Vibrio cholerae, a pair of primers was designed for LAMP. The
      reaction conditions were optimized, and the specificity, sensitivity, and
      practicability of LAMP were tested using 47 bacterial strains and simulated
      contaminated sites. RESULTS: The results of viable bacterium count showed that
      LAMP was capable of detecting Vibrio cholerae at a level as low as 1.6x10(2)
      cfu/ml. The minimal detectable concentration was 1.6+10(3) cfu/ml for simulated
      contaminated samples such as feces and seawater, and 1.6+10(4) cfu/ml for
      contaminated milk. All the 21 strains of Vibrio cholerae yielded positive results
      in LAMP, and the 26 strains of other bacteria all showed negative results, with a
      detection specificity of 100%. CONCLUSION: The established LAMP method has high
      specificity and sensitivity for detecting Vibrio cholerae and is applicable in
      field monitoring and epidemiological study of Vibrio cholerae.

PMID- 19861267
TI  - [Adjuvant effect of transcutaneous electrical acupoint stimulation in propofol
      fentanyl anesthesia in partial mastectomy].
AB  - OBJECTIVE: To evaluate the adjuvant effect of transcutaneous electrical acupoint
      stimulation (TEAS) in propofol-fentanyl anesthesia in partial mastectomy.
      METHODS: Ninety patients undergoing partial mastectomy were randomly divided into
      3 groups (n=30), namely group A with propofol-fentanyl anesthesia (PFVA), group B
      with PFVA and TEAS at Hegu-Laogong and Neiguan-WaiGuan acupoints, and group C
      with PFVA and TEAS at Hegu-Laogong, Neiguan-Waiguan, and bilateral Jianjing
      acupoints. The bispectral index (BIS), heart rate (HR), saturation of pulse
      oxygen (SpO2), blood pressure (BP), the reaction of patients to the incision and
      awakening quality were observed at different time points. Blood samples were
      obtained from the dorsal artery of the foot to determine the levels of adrenaline
      and beta-endorphin using the enzyme-linked immunosorbent assay before TEAS (entry
      into the OR in group A) and at 30 min after TEAS (30 min after entry into the OR
      in group A), 5 min after incision, end of the surgery and awakening. RESULTS:
      Thirty minutes after TEAS (or 30 min after entry into the OR in group A), BIS, BP
      and HR were all decreased significantly in groups B and C (P<0.05) but remained
      stable in group A (P>0.05). The plasma propofol concentration of groups B and C
      were significantly lower than that in group A, and group B had the highest plasma
      propofol concentration (P<0.05). The total dose of propofol in groups B and C
      were decreased by 19% and 27% in comparison with that in group A, respectively.
      Compared with the basal value, the content of beta-endorphin in groups B and C
      increased obviously 30 min after TEAS, being the highest in group C (P<0.05); the
      adrenaline level in groups B and C remained stable after TEAS (P>0.05).
      CONCLUSION: TEAS provides an adjuvant effect in propofol-fentanyl anesthesia and
      obviously enhances the analgesia effect.

PMID- 19861268
TI  - [Relationship between fluorodeoxyglucose uptake and vascular endothelial growth
      factor in early-stage nasophygeal carcinoma].
AB  - OBJECTIVE: To study the overexpression of vascular endothelial growth factor
      (VEGF) and fluorine-18 fluorodeoxyglucose (FDG) uptake in early-stage
      nasopharyngeal carcinoma (NPC) and evaluate their relationship. METHODS: FDG
      positron emission tomography (PET) was performed in forty patients with stage I
      and stage II NPC. The maximum and mean standard uptake values (SUVmax and
      SUVmean, respectively) were measured in each patient, and the expression of VEGF
      was measured on paraffin sections using immunohistochemistry. RESULTS: The FDG
      uptake in the patients were 9.45-/+1.87 (SUVmax) and 6.04-/+1.09 (SUVmean), 8.95
      /+1.91 (SUVmax) and 6.04-/+1.09 (SUVmean) in stage I patients, and 11.55-/+1.70
      (SUVmax) and 7.98-/+1.1 (SUVmean) in stage II patients. The FDG uptake of stage
      II patients was higher than that of stage I patients. The FDG uptake of non
      keratinizing differentiated carcinoma was 9.74-/+1.82 (SUVmax) and 6.82-/+1.23
      (SUVmean) and 10.44-/+2.16 (SUVmax) and 6.68-/+1.35 (SUVmean) in non-keratinizing
      undifferentiated carcinoma, showing no significant differences between them
      (SUVmax: t=1.230, P>0.05; SUVmean: t=0.346, P>0.05). The VEGF-positive cells were
      60.80% in the tumor. A correlation between VEGF expression and FDG uptake in he
      tumor was noted (r=0.460, P=0.03). CONCLUSION: VEGF overexpression is correlated
      to FDG uptake in patients with early-stage NPC. The SUV value reflects the
      glucose metabolism of NPC, and also shows the degree of oxygen insufficiency in
      the tumor tissue.

PMID- 19861269
TI  - [Clinical evaluation of the application of gene chip for identifying pathogens in
      blood cultures].
AB  - OBJECTIVE: To explore the feasibility of using gene chip method to identify
      pathogens in blood cultures. METHODS: Clinical blood samples were obtained and
      cultured using an automated blood culture system. A gene chip diagnostic kit was
      used to detect the pathogenic bacteria in these blood cultures following the
      procedures of target gene extraction and amplification, hybridization and result
      analysis. The conventional method was also used to isolate and identify the
      bacteria from the clinical blood cultures, and the results of the two methods
      were compared. RESULTS: In the 86 clinical blood samples, 74 were positive and 12
      negative according to the conventional method, while 48 were positive and 38
      negative as found by the gene chip method, showing significant differences in the
      results (P<0.05). The two methods only had a concordance rate of 69.77%.
      CONCLUSION: The gene chip diagnostic kit has low concordance rate with the
      conventional method for detecting pathogens in clinical blood cultures and awaits
      further improvement.

PMID- 19861270
TI  - [Effect of low-dose hydroxyurea with sodium butyrate on globin gene expression in
      human erythroid progenitor cells].
AB  - OBJECTIVE: To investigate the effects of combined use of low-dose hydroxyurea
      (HU) and sodium butyrate (NaB) on the expression of 7 globin genes (zeta, alpha,
      epsilon, Ggamma, Agamma, delta, and beta) in human erythroid progenitor cells.
      METHODS: Human erythroid progenitor cells were cultured using a two-step liquid
      culture system and treated with HU and NaB either alone or in combination. The
      inhibitory effects of the agents on the cell growth were monitored with trypan
      blue exclusion assay, and the changes in the mRNA of the 7 globin genes were
      detected using RT-PCR. RESULTS: Low-dose HU combined with NaB resulted in
      significantly lower inhibition rate of the erythroid progenitor cells than
      routine dose HU and NaB used alone (28.56% and 38.80%, respectively, P<0.05).
      Compared with untreated cells (0.653-/+0.092 and 0.515-/+0.048), HU combined with
      NaB significantly increased the expression of Ggamma-and Agamma- mRNA (1.203
      /+0.018 and 0.915-/+0.088, respectively, P<0.05), and HU and NaB used alone
      produced similar effects (1.305-/+0.016 and 0.956-/+0.029 for HU, and 1.193
      /+0.070 and 0.883-/+0.012 for NaB, P>0.05). HU and NaB, either used alone or in
      combination or at different doses, caused no significant changes in the other
      globin genes (zeta, alpha, epsilon, delta and beta) (P>0.05). CONCLUSION: Low
      dose HU combined with NaB can up-regulate gamma globin gene expression,
      especially Ggamma-mRNA expression, to decrease the growth inhibition on human
      erythroid progenitor cells in vitro, but produces no significant effect on the
      expressions of zeta, alpha, epsilon, delta and beta genes.

PMID- 19861271
TI  - [Functional study of the eukaryotic fluorescent expression vector of truncated
      lymphoid enhancer-binding factor 1 (LEF-1) gene in SW480 cells].
AB  - OBJECTIVE: To construct a eukaryotic fluorescent expression vector of truncated
      lymphoid enhancer-binding factor 1 (LEF-1) gene and investigate its effect on the
      proliferation and apoptosis of human colonic carcinoma cell line SW480. METHODS:
      Truncated LEF-1 gene was obtained by PCR and DNA recombination from human
      lymphoid node cDNA library. The PCR product of LEF-1 gene was inserted into the
      plasmid pMD-18T and sequenced. The truncated LEF-1 gene was inserted into the
      eukaryotic expression plasmid pcDNA3.1 and fused with mRFP for tracing. Using
      Lipofectamine 2000, the plasmid pcDNA3.1-LEF-1-mRFP was transfected into Hela
      cells and detected by Western blotting and fluorescence activated cell sorting
      (FACS). The changes in the growth, proliferation and apoptosis of the SW480 cells
      were observed after transfection with the plasmids. RESULTS: The truncated LEF-1
      gene was successfully cloned. After transfection with the plasmid pcDNA3.1-LEF-1
      mRFP, the Hela cells expressed the product of LEF-1 as detected by Western
      blotting and FACS. The growth and proliferation of SW480 cells was inhibited and
      the cell apoptosis increased after transfection with the plasmid pcDNA3.1-LEF-1
      mRFP, which also caused cell cycle arrest in G0/1 phase. CONCLUSION: The
      eukaryotic expression fluorescent vector pcDNA3.1-LEF-1-mRFP has been constructed
      and expressed in eukaryotic cell line successfully. The truncated LEF-1 protein
      expressed in the transfected SW480 cells results in inhibition of the cell growth
      and proliferation with increased cell apoptosis and cell cycle arrest in G0/1
      phase.

PMID- 19861272
TI  - [Epidemiological and clinical analysis of Mycoplasma pneumoniae infection in
      children with acute respiratory tract infection].
AB  - OBJECTIVE: To summarize the epidemiology and clinical characteristics of
      Mycoplasma pneumoniae (MP) infection in children with acute respiratory tract
      infection (ARI) in Guangzhou. METHODS: MP was detected using an indirect
      immunofluorescent method in 2084 children with ARI. The relations between MP
      infection rate and the gender, age, season, site of infection and wheezing
      diseases were analyzed. RESULTS: A total of 433 children (20.8%) were positive
      for MP, including 222 boys (19.8%) and 211 girls (21.9%) without significant
      difference in the infection rate between the genders (P>0.05). In 0- to 3-year
      old group, 106 children were positive for MP (15.0%), while in 3- to 5-year-old
      group and 5- to 14-year-old group, 163 (25.2%) and 164 (22.5%) were positive,
      respectively, showing a significant difference in the infection rate between the
      3 groups (P<0.05). The MP infection rate was 18.0% in January to March, 25.1% in
      April to June, 17.7% in July to September, and 20.5% in October to December,
      showing significant differences between the periods (P<0.05). No significant
      difference was found in the infection rate between children with acute upper
      respiratory tract infection (URI) and those with lower respiratory tract
      infection (LRI) (P>0.05). Among the children with LRI, those having wheezing
      disease had significantly higher MP positivity rate than those without wheezing.
      CONCLUSION: MP is a common causative agent for ARI in children. MP infection is
      not related to gender and infection site, but to age and season. Children over 3
      years old are vulnerable to MP infection. MP infection can be associated with
      wheezing in LRI.

PMID- 19861273
TI  - [Transcatheter arterial chemoembolization with high-dose iodized oil for hepatic
      VX2 tumor in rabbits].
AB  - OBJECTIVE: To evaluate the effect of transcatheter arterial chemoembolization
      (TACE) with high-dose iodized oil on hepatic tumor growth and metastasis in
      rabbits. METHODS: Forty-eight rabbits with implanted VX2 tumor were randomly
      divided into control group, routine dose iodized oil TACE group and high-dose
      iodized oil TACE group to receive perfusion through the hepatic artery with 0.9%
      saline, 5 mg adriamycin with routine-dose iodized oil, and 5 mg adriamycin with
      high-dose iodized oil, respectively. The tumor volume, tumor necrosis,
      intrahepatic and lung metastasis were examined 2 weeks after TACE. RESULTS: No
      significant difference was found in the tumor volume between the 3 groups before
      TACE (P>0.05). The rabbits receiving TACE with iodized oil, especially at the
      high dose, showed significantly reduced tumor volume as compared with the control
      group (P<0.01). TACE with high-dose iodized oil resulted in significantly
      increased tumor necrosis rate in comparison with the control group and TACE with
      a routine dose of iodized oil (P<0.05); high-dose iodized oil TACE was also
      associated with reduced intrahepatic and lung metastasis as compared routine dose
      iodized oil TACE (P<0.05). CONCLUSION: TACE with high-dose iodized oil can
      obviously inhibit the growth and intrahepatic and lung metastasis of transplanted
      VX2 liver tumor in rabbits .

PMID- 19861274
TI  - [Establishment of a digital Evans-Jensen classification model of femoral
      intertrochanteric fracture].
AB  - OBJECTIVE: To establish a digitized Evans-Jensen classification model of femoral
      intertrochanteric fracture. METHODS: The hip of a healthy male volunteer was
      examined with 64-slice spiral CT, and the data were processed using Mimics 10.01
      software to reconstruct the proximal femur model. According to Evans-Jensen
      classification criteria of femoral intertrochanteric fracture, each type of
      fracture model was simulated. Five orthopedic surgeons and 10 medical students
      undertook the preliminary evaluation of the digital fracture model. RESULTS: The
      digital fracture model is intuitive, three-dimensional, and realistic with good
      visual effect. The fracture could be observed and charted from optional direction
      and angle. The corresponding animation allowed 360 degrees rotation. Evaluation
      by the 4 orthopedic surgeons and 10 medical students confirmed that the digital
      fracture model was intuitive and easy to understand. CONCLUSION: The digital
      model of femoral intertrochanteric fracture is intuitive, three-dimensional,
      realistic and dynamic, and may help in clinical practice and medical teaching.

PMID- 19861275
TI  - [Expression of caspase-3 in rat kidney with renal tubular damage induced by
      lipopolysaccharide and hypoxia].
AB  - OBJECTIVE: To observe the expression of caspase-3 in the kidney of a rat model of
      renal tubular damage induced by endotoxin and hypoxia and explore the mechanism
      of renal tubular damage. METHODS: Ten rats were anesthetized with artificial
      ventilation and received 2 mg/kg lipopolysaccharide (LPS) injection through the
      penile vein. The FiO2 was reduced 90 min later from 21% to 5%, and the
      ventilation was withdrawn after another 90 min. Immediately after ventilation
      withdrawal, the kidney of the rats were obtained for immunocytochemistry and HE
      staining. RESULTS: HE staining showed obvious hyperemia in most of the glomeruli,
      mild swelling of the endothelial and mesangial cells, severe swelling and
      turbidity in the proximal tubular epithelial cells without obvious changes in
      most of the distal proximal tubules. A small portion of the interstitial
      epithelial cells showed swelling and turbidity, and the entire renal interstitium
      appeared hyperemic but without inflammatory cell infiltration.
      Immunocytochemistry detected the presence of caspase-3 in the cytoplasm, and most
      of the distal renal tubule cells were positive for caspase-3, while only
      occasional cells showed caspase-3 positivity in the proximal tubular epithelial
      cells. Most of the proximal tubular epithelial and glomerulus cells were negative
      for caspase-3. CONCLUSIONS: Endotoxin and hypoxia can induce renal damage,
      particularly in the proximal renal tubule cells, and the distal tubular
      epithelial cells sustain relatively light damage. Caspase-3 is strongly expressed
      in the distal renal tubular cells, suggesting that in renal tubular damage
      induced by endotoxin and hypoxia, cell degeneration, necrosis and apoptosis
      coexist in the tubular epithelial cells; degeneration and necrosis occur
      primarily in the proximal tubular epithelial cells, while apoptosis is obvious in
      the distal renal cells.

PMID- 19861276
TI  - [Cone-beam pseudo lambda tomography under FDK framework].
AB  - The medical CT scanner is rapidly evolving from the fan-beam mode to the cone
      beam geometry mode. In this paper, a new cone-beam pseudo Lambda tomography was
      proposed based on the Noo's fan beam super-short scan formula and FDK framework.
      The proposed pseudo-LT algorithm, which avoids the computation of any PI line and
      any differential operation, has a significant practical implementation, thus
      leading to the images with quality improvement and reduced artifacts. The results
      in the simulation studies confirm the observation that the new algorithm can
      improve the image resolution over the traditional algorithms with noise
      projection data.

PMID- 19861277
TI  - [Association of blood glucose fluctuation with the pain sensation in patients
      with painful diabetic neuropathy].
AB  - OBJECTIVE: To investigate the relationship between blood glucose fluctuation and
      the pain sensation in patients with painful diabetic neuropathy. METHODS: The
      severity of pain in 16 patients with painful diabetic neuropathy was assessed
      using visual analog scale (VAS), and according to the results, the patients were
      divided into mild to moderate pain group and severe pain group. The blood glucose
      of the patients were monitored continuously for 72 h using a continuous glucose
      monitoring system, and the MBG, SD, DMMG, MAGE, and AUCPG were obtained with the
      FBG and HbA1C tested. RESULTS: The SD, DMMG, and MAGE of the severe pain group
      were all significantly higher than those of the mild to moderate pain group
      (P<0.05), and no significant difference was found in MBG, FBG or HbA1c between
      the two groups. CONCLUSION: The blood glucose fluctuation is associated with the
      severity of the pain degree, and effective control of the blood glucose
      fluctuation helps prevent and treat painful diabetic neuropathy.

PMID- 19861278
TI  - [Detection of serum autoantibodies to melanocyte and correlation between melanoma
      antigen recognized by T-cells and vitiligo in children].
AB  - OBJECTIVE: To detect the serum levels of melanocyte antibodies and explore the
      relation between melanoma antigen recognized by T-cells (MART-1) and vitiligo in
      children. METHODS: The serum samples were collected from children with vitiligo
      to test the autoantibodies, and divided into low- and high-titer group according
      to the test results. Melanocytes were incubated with the serum samples, and the
      changes of melanocyte surface antigen were evaluated using specific MART-1
      antibody. RESULTS: The serum melanocyte antibody levels in children with vitiligo
      were significantly higher than those in normal subjects. The expression level of
      melanocyte surface antigen MART-1 increased obviously after incubation of the
      melanocyte with high antibody titer serum samples, and MART-1 was found to
      specifically bind to specific MART-1 antibody. CONCLUSION: Melanocytes MART-1 may
      correlate to the autoimmune mechanism in children with vitiligo.

PMID- 19861279
TI  - [Multiplex fluorescent quantitative PCR for detecting deep fungal infection in
      patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To establish a rapid, sensitive and specific method based on multiplex
      fluorescent quantitative PCR for detection of deep infections with Candida
      albicans and Aspergillus flavus in patients with systemic lupus erythematosus
      (SLE). METHODS: Two pairs of primers and Taqman probes were designed according to
      the gene sequences of Candida albicans and Aspergillus flavus available in
      American Type Culture Collection. The positivity rate, sensitivity and
      specificity of the multiplex fluorescent quantitative PCR-based method for
      detecting the fungal infection was tested in 20 specimens from SLE patients with
      Candida albicans and Aspergillus flavus infections, 20 specimens from SLE
      patients with suspected deep fungal infections, and 20 microbial samples other
      than Candida albicans or Aspergillus flavus. RESULTS: The multiple fluorescence
      quantitative PCR-based method showed a positivity rate and specificity of both
      100% for detecting Candida albicans and Aspergillus flavus infections in the SLE
      patients. This method resulted in a detection sensitivity of 75%, significantly
      higher than that of fugal culture method (40%, P<0.05). CONCLUSIONS: The
      multiplex fluorescent real-time PCR-based method allows rapid, quantitative and
      simultaneous detection of deep Candida albicans and Aspergillus flavus infections
      with high sensitivity and specificity in SLE patients.

PMID- 19861280
TI  - [Value of ultrasonographic grading with high-frequency probes in distinguishing
      breast tumors].
AB  - OBJECTIVE: To investigate the value of ultrasonographic grading with high
      frequency probes in differentiating benign and malignant breast tumors. METHODS:
      Sixty-four women (mean age 44.5-/+13.7 years) with 79 breast tumors underwent
      high-frequency ultrasonography to examine the tumor number, size, aspect ratio,
      shape, boundaries, encapsulation, pseudopod, internal and rear echoes,
      calcifications, blood perfusion, abnormality lymph nodes in the axilla. The
      tumors were graded based on these findings using a 10-point grading system.
      RESULTS: Between the 46 women with benign tumors and 18 with malignant tumors, no
      significant differences were found in the mean tumor number (1.5-/+1.3 vs 1.1
      /+0.3, P>0.05) or size (55.0-/+19.2 mm vs 19.8-/+8.3 mm, P>0.05), but the mean
      age (41.4-/+12.4 years vs 52.4-/+14.1 years) and ultrasonographic grade (2.8
      /+2.2 vs 7.3-/+1.7, P<0.05) differed significantly. The ultrasonographic grade of
      the breast tumors showed an obvious correlation to the nature of the tumors
      (r=0.695, P<0.001). CONCLUSION: Grading of breast tumors with high-frequency
      ultrasonography helps evaluate the nature of the tumors, and a higher score
      suggests increased probability of malignancy.

PMID- 19861281
TI  - [Cochlear implant in patients with congenital malformation of the inner ear].
AB  - OBJECTIVE: To summarize the clinical experience with multi-channel cochlear
      implantation in patients with inner ear malformations and evaluate and the
      outcomes of speech rehabilitation. METHODS: A retrospective study was conducted
      in 295 patients receiving cochlear implantation from 1998 to 2007, including 25
      patients with large vestibular aqueduct syndrome (LVAS), 9 with Modini
      malformation, and 5 with common cavity deformity. All the patients received the
      Nucleus24 cochlear implants. In LVAS cases, 4 had Nucleus 24R (ST) implants, 8
      had Contuor implants, 10 had Contuor Advance, and the remaining cases used
      Nucleus24(M) straight-electrode implants. RESULTS: Severe gusher appeared in 3
      cases of LVAS, and perilymph fluctuation were seen in other 15 cases. Four
      patients with Mondini malformation and 2 with common cavity malformation also
      experienced severe gusher, but the electrodes were inserted smoothly in all the
      patients without postoperative facial paralysis or cerebrospinal fluid leakage.
      The hearing threshold in these patients was similar to that in patients with
      normal cochlear structure. After speech rehabilitation for over 6 months, the
      abilities of speech discrimination and spoken language improved in all the cases
      in comparison with the preoperative lingual functions. CONCLUSION: Multi-channel
      cochlear implantation can be performed in patients with inner ear malformation,
      but should not be attempted in patients with poor cochlear and cochlear nerve
      development. A comprehensive pre-operative radiographic and audiological
      evaluation is essential.

PMID- 19861282
TI  - [Smad7 inhibits collagen expression in human hepatic satellite cells in vitro].
AB  - OBJECTIVE: To investigate the effect of Smad7 on the expressions of collagen I
      and alpha-smooth muscle actin (alpha-SMA) in HSC-T6 cell line activated by
      transforming growth factor-beta1 (TGF-beta1). METHODS: HSC-T6 cells stably
      expressing M2-flag protein were selected after co-infection of the cells with
      pTRE-Smad7-M2-flag and pTet-on. The optimal dose of doxycycline for inducing
      Smad7 was determined, and the effects of Smad7 over-expression on the expressions
      of collagen I and alpha-SMA in the cells activated by TGF-beta1 and on Smad2/3
      phosphorylation were evaluated using Western blotting. RESULTS: The optimal dose
      of doxycycline for inducing Smad7 expression was 2 mg/L. Smad7 over-expression
      induced by doxycycline decreased the expressions of collagen I and alpha-SMA in
      HSC-T6 cells activated by TGF-beta1, and down-regulated the level of Smad2/3
      phosphorylation. CONCLUSION: Smad7 over-expression inhibits Smad2/3
      phosphorylation, and decreases the expression of collagen I and alpha-SMA in HSC
      T6 cells induced by TGF-beta1 to inhibit the progression of liver fibrosis.

PMID- 19861283
TI  - [Effect of plasma fibrinogen level-based defibrase therapy in patients with acute
      cerebral infarction].
AB  - OBJECTIVE: To evaluate the therapeutic effect of individualized defibrase therapy
      according to the level of plasma fibrinogen (FIB) in patients with acute cerebral
      infarction (ACI). METHODS: Sixty patients with ACI (within 72 h after onset) were
      randomly divided into defibrase group (n=30) and control group (n=30). The
      patients in defibrase group received intravenous defibrase infusion at different
      first doses (15, 10, and 5 U) according to plasma FIB level (>4 g/L, 2-4 g/L, and
      1.3-2 g/L) before treatment. Plasma FIB was measured every 12 h after the first
      dose of defibrase, and when plasma FIB was over 1.3 g/L, intravenous infusion of
      5 U defibrase was given to maintain plasma FIB within the range of 0.70-1.13 g/L
      over a period of 7 days. The plasma prothrombin time (PT), activated partial
      thromboplastin time (APTT) and FIB before and after the 7-day treatment were
      measured, and the scores of Chinese stroke scale (CSS) after 14 days of treatment
      and Activity of Daily Living (ADL) after 3 months were recorded. RESULTS: After 7
      days of treatment, plasma PT and APTT were significantly prolonged lengthened and
      plasma FIB was lowered in defibrase group. The scores of CSS improved in
      defibrase group after 14 days of treatment, showing significant difference from
      those of the control group. The clinical effective rate was 80% in defibrase
      group, significantly higher than that in the control group (50%). The scores of
      ADL after 3 months were similar between the 2 groups, but the percentage of
      independent living and mild dependency was significantly higher in defibrase
      group (93.3% vs 70.0%). No intracerebral and extracerebral hemorrhage occurred in
      defibrase group the during treatment, no did death occur after 3 months of
      treatment. CONCLUSION: Defibrase therapy based on plasma FIB level can rapidly
      and effectively lower plasma FIB, reduce neurological impairment and improve the
      quality of life in patients with ACI.

PMID- 19861284
TI  - [Effects of lipopolysaccharides of Bacterium prodigiosum on tumor growth and
      immunosuppression in mice].
AB  - OBJECTIVE: To observe the effects of lipopolysaccharides of Bacterium prodigiosum
      (BP-LPS) in inhibiting tumor growth and improving immunosuppression in mice.
      METHODS: In mice bearing S180 tumor and a mouse model of immunosuppression
      induced by cyclophosphamide (CTX), the tumor growth, indexes of the immune organs
      and peripheral white blood cell count were measured after intraperitoneal
      injection of BP-LPS. RESULTS: Injections of BP-LPS (40 U/kg) for 8 consecutive
      days resulted in a significant inhibition of the tumor growth in mice bearing
      S180 tumor (P<0.01), with a dose-dependent increase of the spleen indexes but no
      obvious changes in the thymus indexes. Intraperitoneal injections of BP-LPS for 7
      days inhibited the reduction of peripheral white blood cells and spleen indexes
      in immunosuppressive mice, but did not produce any significant changes in normal
      mice. CONCLUSION: BP-LPS can inhibit the tumor growth in tumor-bearing mice and
      enhance the immune functions of immunosuppressive mice.

PMID- 19861285
TI  - [Role of prostate stem cell antigen in human pancreatic carcinoma: a tissue
      microarray-based study].
AB  - OBJECTIVE: To investigate the expression of prostate stem cell antigen (PSCA) in
      human pancreatic carcinoma and explore its role in the oncogenesis of pancreatic
      cancer. METHODS: A pancreatic carcinoma tissue microarray was constructed, which
      contained 10 normal adult pancreas tissues, 12 chronic pancreatitis tissues and
      78 pancreatic carcinomas. Immunohistochemistry was employed to detect the
      expression of PSCA, and the relation between PSCA expression and the
      clinicopathological factors of pancreatic carcinoma was analyzed. RESULTS: The
      positivity rate of PSCA in pancreatic carcinoma was 79.5% (62/78), and PSCA
      staining was more intense in the malignant cells than in the benign cells
      (chi2=15.81, P<0.005) and chronic pancreatitis tissues (chi2=11.33, P<0.005). No
      obvious association was found between PSCA expression and the other variables of
      pancreatic carcinoma (including gender, age at surgery, tumor grade, and TNM
      stages). CONCLUSION: The expression of PSCA can be related to the development of
      pancreatic cancer, but not to the clinicopathological factors of the tumor.

PMID- 19861286
TI  - [Expression of transcription factors T-bet and GATA-3 in peripheral blood
      mononuclear cells from patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the role of transcription factors T-bet and GATA-3 in
      the pathogenesis of systemic lupus erythematosus (SLE). METHODS: The expression
      of T-bet and GATA-3 mRNA in the peripheral blood mononuclear cells (PBMCs) of 60
      patients with SLE and 20 normal control subjects were detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Compared with the
      normal controls, T-bet mRNA expression decreased whereas GATA-3 mRNA expression
      increased significantly in patients with SLE, active SLE and inactive SLE.
      CONCLUSIONS: The high expression of GATA-3 promotes the immature T cells to
      differentiate into Th2 cells, induces Th2 cells to secrete the cytokines IL-6 and
      IL-10, which, along with the low expression of Th1 as a result of T-bet
      expression inhibition, causes B cell activation to produce a large quantity of
      autoantibodies, leading finally to multiple organ injuries. Effective regulation
      of GATA-3 expression may provide a new clue for the treatment of SLE.

PMID- 19861287
TI  - [From lipid target values to the JUPITER study. Significance of achieving lipid
      levels specified by the guidelines and deficiencies in practice].
AB  - In Hungary the life expectancy have increased by 4.14 years between 1993 and 2006
      and the improvement of cardiovascular mortality contributed to this with 1.85
      years. Lipid lowering therapy and achievement of target lipid levels have become
      recently a crucial point of cardiovascular prevention. Despite the improving
      tendency the rate of achieving LDL-cholesterol goal is not higher than 1/3 and
      its main cause seems to be the fact that greater part of the physicians (56% of
      them in year 2007) - seeing the results with not convenient lipid levels - yield
      to it, do not modify the current treatment. However, there is growing evidence
      that the lower LDL-cholesterol level improves not only the clinical outcome but
      it is cost-effective as well. The most important trial performed recently using
      statin was the JUPITER study, in which patients with normal lipid levels and high
      hs-CRP level without known atherosclerotic disease were treated with 20 mg
      rosuvastatin or placebo. The primary endpoint (cardiovascular mortality, stroke,
      non fatal myocardial infarction, unstable angina and revascularization) decreased
      significantly by 44% and total mortality decreased by 20%. For the prevention of
      one primary event 23 patients for 5 years were necessary to be treated. The
      results raise the need for reconsidering principles and target levels of the
      primary prevention and warn that in the lipid lowering therapy a greater emphasis
      should be placed on the hs-CRP level.

PMID- 19861288
TI  - [Results of immuno-chemotherapeutic treatment of patients with diffuse large B
      cell lymphoma].
AB  - Treatment with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)
      has been considered as the standard therapy for diffuse large B-cell lymphoma
      (DLBCL) for more than 20 years. CHOP treatment in combination with targeted
      immunotherapy, rituximab (R-CHOP), resulted in significant improvements in the
      treatment of this group of patients. In this study, efficacy of R-CHOP and R-CHOP
      like treatments was analysed. Results were compared to the data of historical
      patients only receiving CHOP treatment or CHOP-like treatment. Between September
      2002 and April 2005, 140 newly diagnosed, untreated DLBCL patients started to
      receive R-CHOP treatment in a single centre. The eligibility criteria included
      advanced stage (clinical stages III-IV), or large tumour size (>7 cm) and/or
      symptom B or extranodal manifestation in the case of clinical stages I-II. The
      results were compared to the data of 130 patients only receiving CHOP treatment
      in the past. In the patients receiving R-CHOP, the therapeutic outcomes were
      superior for all parameters. During an average follow-up period of 44 or 52
      months, the overall remission rate was 73.6% in the R-CHOP group in comparison
      with 47.7% in the CHOP group. The 5-year overall survival was 68.6% vs. 41.0%
      (RR: 0.4293, CI: 0.2963-0.6221; p < 0.0001), the event-free survival was 59.8%
      vs. 33.5% (RR: 0.5038, CI: 0.3606-0.7038; p < 0.0001) and the progression-free
      survival was 64.4% vs. 37.6% (RR: 0.4915, CI: 0.3442-0.7019; p < 0.0001). Since
      prognostic parameters were more favourable in the R-CHOP group, patient groups
      were also compared using the International Prognostic Index score. Again,
      significant differences were revealed by the subgroup analyses. The 5-year
      overall survival was 74.4% vs. 47.9% (RR: 0.4475, CI: 0.2418-0.8285; p = 0.0084)
      and 52.0% vs. 28.8% (RR: 0.4989, CI: 0.3098-0.8035; p = 0.003) in the group with
      good prognosis and in the group with poor prognosis, respectively. In the group
      with very good prognosis, the statistical difference between the two groups in
      terms of the 5-year survival parameters remained undetectable as a result of the
      already very high therapeutic effect and low case number (OS and EFS: CHOP: 100%
      and 62.5% vs. R-CHOP: 90.9% and 87.0%; p = 0.3873 and p = 0.1702). Combining the
      standard CHOP treatment with rituximab resulted in a significant improvement of
      the therapeutic outcomes irrespective of the prognostic grouping. The data are
      comparable with those reported in the international literature.

PMID- 19861289
TI  - [Nutritional status and nutritional rehabilitation of elderly people living in
      long-term care institutions].
AB  - We review our studies on the most important factors related to feeding and
      nutrition in long-term care institutions, as well as we present the nutritional
      status of elderly people living in social homes, and, based on our results, we
      make recommendations concerning nutritional rehabilitation. AIMS: We aimed to
      assess the following: nutritional status of people older than sixty years
      (elderly) living in long-term care institutions; changes in the body mass index
      of elderly living in long-term care institutions; changes in the nutritional
      status of elderly living in long-term care institutions during the last half
      decade; relations and correlations between acute and chronic diseases and
      nutritional status; the sip feed provision for elderly living in long-term care
      institutions; relationship between the discovered potential influencing factors
      and nutritional status screened by Malnutrition Universal Screening Tool (MUST).
      METHODS: We screened the nutritional status of altogether 4774 (men: 28.9-30.9%,
      women: 69.1-71.19%; mean age: 77.8+/-8.9 years) elderly long-term care residents
      who volunteered to participate. In 2004 and 2006 the MUST and our questionnaire,
      in 2008 the nutritionDay questionnaire was used. RESULTS: Risk of malnutrition is
      high (26.8-77.0%) in elderly residents of social homes. Assessment of nutritional
      status is done four times a year or even more rarely in 29.5% of the residents.
      Nutritional status is multifactorial; it is influenced by immobility, fever, etc.
      Loss of appetite and swallowing difficulties are 2.5-fold, limited mobility,
      dementia and missing teeth are almost two-fold (1.6-1.7) more frequent in the
      group of high risk elderly than in the elderly living in social homes.
      Neurological diseases are in a significant correlation with nutritional status.
      Incidence of neurological diseases increased significantly in the last years.
      CONCLUSION: Nutritional rehabilitation does not end with screening the
      nutritional status, moreover, it begins with that. Individual diet has to follow
      the determination of personal nutritional guidelines.

PMID- 19861290
TI  - [Father of social paediatrics: Paracelsus medal to Prof. Theodor Hellbrugge
      (89)].

PMID- 19861292
TI  - [Myoanabolic steroids and selective androgen receptor modulators: mechanism of
      action and perspectives].
AB  - Interest in anabolic steroids has been renewed in the last decade with the
      discovery of tissue-selective androgen receptor modulators exhibiting high
      myotropic and small androgenic activity. An explanation put forward by us in 1982
      for the mechanism of the preferential myotropic effect of nandrolone (19
      nortestosterone) exploits the fundamental difference between the 5alpha-reductase
      concentrations in skeletal muscle and androgenic target tissue. In androgenic
      tissue, testosterone is converted to the more potent 5alpha-dihydrotestosterone
      whereas nandrolone is converted to a less potent derivative. As 5alpha-reduction
      is negligible in skeletal muscle, this explains why nandrolone shows a greater
      myotropic to androgenic ratio when compared with testosterone. Anabolic steroids
      that do not undergo 5alpha-reduction exert myotropic-androgenic dissociation
      because their effect in androgenic tissues is not amplified by 5alpha-reduction.
      Tissue selectivity by receptor modulators may be achieved by inducing specific
      conformational changes of the androgen receptor that affect its interaction with
      transcriptional coregulators. Anabolic activity is mediated by the stimulation of
      ribosomal RNA synthesis therefore regulation of this synthesis by anabolic
      steroids would deserve detailed studies.

PMID- 19861293
TI  - [Link between diabetes and diastolic dysfunction and the diagnostic role of
      echocardiography].
AB  - Diabetes mellitus, a disease that has been reaching epidemic proportions, is an
      important risk factor to the development of cardiovascular complication. The left
      ventricular diastolic dysfunction represents the earliest pre-clinical
      manifestation of diabetic cardiomyopathy, preceding systolic dysfunction and
      being able to evolve to symptomatic heart failure. In early stages, these changes
      appear reversible with tight metabolic control, but as pathologic processes
      become organized, the changes are irreversible and contribute to an excess risk
      of heart failure among diabetic patients. Doppler echocardiography provides
      reliable data in the stages of diastolic function, as well as for systolic
      function. Combination of pulsed tissue Doppler study of mitral annulus with
      transmitral inflow may be clinically valuable for obtaining information about
      left ventricular filling pressure and unmasking Doppler inflow pseudonormal
      pattern, a hinge point for the progression toward advanced heart failure.
      Subsequently we give an overview about diabetes and its complications, their
      clinical relevance and the role of echocardiography in detection of diastolic
      heart failure in diabetes.

PMID- 19861294
TI  - [Pentalogy of Cantrell: six new cases].
AB  - Cantrell's pentalogy is a rare multiple malformation syndrome consisting of
      supraumbilical abdominal wall defect, sternal defect, pericardial defect,
      anterior diaphragmatic defect and heart malformation. AIMS AND METHODS: Prenatal
      ultrasound findings and malformations described during autopsy of the Cantrell's
      pentalogy cases diagnosed between January 1991 and June 2009 in our institute
      were reviewed. A literature research was conducted to analyze the prevalence and
      prenatal detection rate of the five previously described malformations and
      ectopia cordis in the Cantrell's pentalogy cases. RESULTS: Six cases of
      Cantrell's pentalogy were diagnosed during the study period in our department.
      Sonography detected multiple malformations in 3 cases, and isolated malformation
      in 3 cases. Analyzing the data of 49 Cantrell's pentalogy cases altogether showed
      that, beside abdominal wall defect and ectopia cordis which had the highest
      prenatal detection rate (83% and 91% with a prevalence of 94% and 69%,
      respectively), sternal defect and anterior diaphragmatic hernia were also present
      in a large number of the cases (80% and 73% respectively). CONCLUSION:
      Sonographic identification of the sternal defect or diaphragmatic hernia may help
      to differentiate Cantrell's pentalogy from malformations part of the syndrome but
      occurring as isolated defects.

PMID- 19861295
TI  - [The history of coronary surgery. Attila Arvay memorial lecture].

PMID- 19861297
TI  - A web-based nutrition program reduces health care costs in employees with cardiac
      risk factors: before and after cost analysis.
AB  - BACKGROUND: Rising health insurance premiums represent a rapidly increasing
      burden on employer-sponsors of health insurance and their employees. Some
      employers have become proactive in managing health care costs by providing tools
      to encourage employees to directly manage their health and prevent disease. One
      example of such a tool is DASH for Health, an Internet-based nutrition and
      exercise behavior modification program. This program was offered as a free, opt
      in benefit to US-based employees of the EMC Corporation. OBJECTIVE: The aim was
      to determine whether an employer-sponsored, Internet-based diet and exercise
      program has an effect on health care costs. METHODS: There were 15,237 total
      employees and spouses who were included in our analyses, of whom 1967 enrolled in
      the DASH for Health program (DASH participants). Using a retrospective, quasi
      experimental design, study year health care costs among DASH participants and non
      participants were compared, controlling for baseline year costs, risk, and
      demographic variables. The relationship between how often a subject visited the
      DASH website and health care costs also was examined. These relationships were
      examined among all study subjects and among a subgroup of 735 subjects with
      cardiovascular conditions (diabetes, hypertension, hyperlipidemia). Multiple
      linear regression analysis examined the relationship of program use to health
      care costs, comparing study year costs among DASH participants and non
      participants and then examining the effects of increased website use on health
      care costs. Analyses were repeated among the cardiovascular condition subgroups.
      RESULTS: Overall, program use was not associated with changes in health care
      costs. However, among the cardiovascular risk study subjects, health care costs
      were US$827 lower, on average, during the study year (P= .05; t(729) = 1.95).
      Among 1028 program users, increased website use was significantly associated with
      lower health care costs among those who visited the website at least nine times
      during the study year (US$14 decrease per visit; P = .04; t(1022) = 2.05), with
      annual savings highest among 80 program users with targeted conditions (US$55
      decrease per visit; P < .001; t(74) = 2.71). CONCLUSIONS: An employer-sponsored,
      Internet-based diet and exercise program shows promise as a low-cost benefit that
      contributes to lower health care costs among persons at higher risk for above
      average health care costs and utilization.

PMID- 19861298
TI  - Challenges to using an electronic personal health record by a low-income elderly
      population.
AB  - BACKGROUND: Electronic personal health records (PHRs) are increasingly recognized
      and used as a tool to address various challenges stemming from the scattered and
      incompatible personal health information that exists in the contemporary US
      health care system. Although activity around PHR development and deployment has
      increased in recent years, little has been reported regarding the use and utility
      of PHRs among low-income and/or elderly populations. OBJECTIVE: The aim was to
      assess the use and utility of PHRs in a low-income, elderly population. METHODS:
      We deployed a Web-based, institution-neutral PHR system, the Personal Health
      Information Management System (PHIMS), in a federally funded housing facility for
      low-income and elderly residents. We assessed use and user satisfaction through
      system logs, questionnaire surveys, and user group meetings. RESULTS: Over the 33
      month study period, 70 residents participated; this number was reduced to 44 by
      the end of the study. Although the PHIMS was available for free and personal
      assistance and computers with Internet connection were provided without any cost
      to residents, only 13% (44/330) of the eligible residents used the system, and
      system usage was limited. Almost one half of the users (47%, 33/70) used the
      PHIMS only on a single day. Use was also highly correlated with the availability
      of in-person assistance; 77% of user activities occurred while the assistance was
      available. Residents' ability to use the PHR system was limited by poor computer
      and Internet skills, technophobia, low health literacy, and limited
      physical/cognitive abilities. Among the 44 PHIMS users, 14 (32%) responded to the
      questionnaire. In this selected subgroup of survey participants, the majority
      (82%, 9/11) used the PHIMS three times or more and reported that it improved the
      quality of overall health care they received. CONCLUSIONS: Our findings suggest
      that those who can benefit the most from a PHR system may be the least able to
      use it. Disparities in access to and use of computers, the Internet, and PHRs may
      exacerbate health care inequality in the future.

PMID- 19861299
TI  - Preoperative NT-proBNP and CRP predict perioperative major cardiovascular events
      in non-cardiac surgery.
AB  - OBJECTIVE: To investigate whether simple and non-invasive measurement of N
      terminal pro-brain natriuretic peptide (NT-proBNP) and/or C-reactive protein
      (CRP) can predict perioperative major cardiovascular event (PMCE). DESIGN:
      Prospective, single-centre, cohort study. SETTING: A 1900-bed tertiary-care
      university hospital in Seoul, Korea Design and PATIENTS: The predictive power of
      NT-proBNP, CRP and Revised Cardiac Risk Index (RCRI) for the risk of PMCE
      (myocardial infarction, pulmonary oedema or cardiovascular death) were evaluated
      from a prospective cohort of 2054 elective major non-cardiac surgery patients.
      Optimal cut-off values were derived from receiver operating characteristic curve
      (ROC) analysis. MAIN OUTCOME MEASUREMENT: PMCE (myocardial infarction, pulmonary
      oedema or cardiovascular death) within postoperative 30 days. RESULTS: PMCE
      developed in a total of 290 patients (14.1%). Each increasing quartile of NT
      proBNP or CRP level was associated with a greater risk of PMCE after adjustment
      for traditional clinical risk factors. The relative risk (RR) of highest versus
      lowest quartile was 5.2 for NT-proBNP (p<0.001) and 3.7 for CRP (p<0.001). Both
      NT-proBNP (cut-off = 301 ng/l) and CRP (cut-off = 3.4 mg/l) predicted PMCE better
      than RCRI (cut-off = 2) by ROC analysis (p<0.001). Moreover, the predictive power
      of RCRI (adjusted RR = 1.5) could be improved significantly by addition of CRP
      and NT-proBNP to RCRI (adjusted RR 4.6) (p<0.001). CONCLUSIONS: High preoperative
      NT-proBNP or CRP is a strong and independent predictor of perioperative major
      cardiovascular event in non-cardiac surgery. The predictive power of current
      clinical risk evaluation system would be strengthened by these biomarkers.

PMID- 19861300
TI  - Depression and cardiac risk: present status and future directions.

PMID- 19861301
TI  - Three-dimensional echocardiography.
AB  - Over the past two to three decades echocardiography has come a considerable
      distance from the early M-mode machines, and has become an indispensable
      diagnostic tool in any cardiovascular department. It has long been proved to be
      safe and cost-effective, and its clinical versatility has steadily increased with
      the continued integration of newer techniques, such as two-dimensional and
      harmonic imaging, Doppler and much more. One of the more recent developments in
      the field is three-dimensional echocardiography (3DE). 3DE, in various forms, has
      been used as a research tool for many years now, but lately improvements in
      software and transducer technology have begun to facilitate its integration into
      clinical practice. As with any technique, 3DE has its strengths and weaknesses,
      and these must be fully appreciated if it is to be utilised effectively.

PMID- 19861302
TI  - Mutations of FUS gene in sporadic amyotrophic lateral sclerosis.
AB  - BACKGROUND: Mutations in the FUS gene have recently been discovered to be a major
      cause of familial amyotrophic lateral sclerosis (FALS). OBJECTIVE: To determine
      the identity and frequency of FUS gene mutations in a large cohort of Italian
      patients enriched in sporadic cases (SALS). METHODS: Exons 5, 6, 14 and 15 of the
      FUS gene were screened for mutations in 1009 patients (45 FALS and 964 SALS). The
      genetic analysis was extended to the entire coding sequence of FUS in all the
      FALS and 293 of the SALS patients. RESULTS: Seven missense mutations (p.G191S,
      p.R216C, p.G225V, p.G230C, p.R234C, p.G507D and p.R521C) were identified in nine
      patients (seven SALS and two FALS), and none in 500 healthy Italian controls. All
      mutations are novel except for the p.R521C mutation identified in one SALS and
      one FALS case. Both patients showed a similar unusual presentation, with
      proximal, mostly symmetrical, upper limb weakness, with neck and axial
      involvement. With the exception of p.G507D and p.R521C, the mutations identified
      in SALS patients are all localised in the glycine-rich region encoded by exon 6.
      In addition, eight different in-frame deletions in two polyglycine motifs were
      detected, the frequency of which was not significantly different in patients and
      controls. CONCLUSIONS: The results show that FUS missense mutations are present
      in 0.7% of Italian SALS cases, and confirm the previous mutational frequency
      reported in FALS (4.4%). An unusual proximal and axial clinical presentation
      seems to be associated with the presence of the p.R521C mutation.

PMID- 19861303
TI  - Recent changes in breast cancer incidence in Spain, 1980-2004.
AB  - BACKGROUND: Since the 1980s, Spain experienced two decades of sharply increasing
      breast cancer incidence. Declines in breast cancer incidence have recently been
      reported in many developed countries. We examined whether a similar downturn
      might have taken place in Spain in recent years. METHODS: Cases of invasive
      female breast cancer were drawn from all population-based Spanish cancer
      registries that had at least 10 years of uninterrupted registration over the
      period 1980-2004. Overall and age-specific changes in incidence rates were
      evaluated using change-point Poisson models, which allow for accurate detection
      and estimation of trend changes. All statistical tests were two-sided. RESULTS: A
      total of 80,453 incident cases of invasive breast cancer were identified. Overall
      age- and registry-adjusted incidence rates rose by 2.9% (95% confidence interval
      [CI] = 2.7% to 3.1%) annually during the 1980s and 1990s; there was a
      statistically significant change in this trend in 2001 (95% CI = 1998 to 2004; P
      value for the existence of a change point <.001), after which incidence declined
      annually by 3.0% (95% CI = 1.8% to 4.1%). This trend differed by age group: There
      was a steady increase in incidence for women younger than 45 years, an abrupt
      downturn in 2001 for women aged 45-64 years, and a gradual leveling off in 1995
      for women aged 65 years or older. Separate analyses for registries that had at
      least 15 years of uninterrupted registration detected a statistically significant
      interruption of the previous upward trend in breast cancer incidence in provinces
      that had aggressive breast cancer screening programs and high screening
      participation rates, including Navarra (change point = 1991, P < .001), Granada
      (change point = 2002, P = .003), Bizkaia (change point = 1998, P < .001),
      Gipuzkoa (change point = 1998, P = .001), and Araba (change point = 1997, P =
      .002). CONCLUSIONS: The recent downturn in breast cancer incidence among Spanish
      women older than 45 years is best explained by a period effect linked to
      screening saturation.

PMID- 19861304
TI  - Cancer risk from extreme stressors: lessons from European Jewish survivors of
      World War II.

PMID- 19861305
TI  - Cancer incidence in Israeli Jewish survivors of World War II.
AB  - BACKGROUND: Israeli Jews of European origin have high incidence rates of all
      cancers, and many of them were exposed to severe famine and stress during World
      War II. We assessed cancer incidence in Israeli Jewish survivors of World War II.
      METHODS: Cancer rates were compared in a cohort of 315 544 Israeli Jews who were
      born in Europe and immigrated to Israel before or during World War II (nonexposed
      group, n = 57 496) or after World War II and up to 1989 (the exposed group, ie,
      those potentially exposed to the Holocaust, n = 258 048). Because no individual
      data were available on actual Holocaust exposure, we based exposure on the
      immigration date for European-born Israeli Jews and decided against use of the
      term "Holocaust survivors," implying a known, direct individual Holocaust
      exposure. Cancer incidences were obtained from the Israel National Cancer
      Registry. Relative risk (RR) estimates and 95% confidence intervals (95% CIs)
      were calculated for all cancer sites and for specific cancer sites, stratified by
      sex and birth cohort, and adjusted for time period. RESULTS: The nonexposed group
      contributed 908 436 person-years of follow-up, with 13 237 cancer diagnoses
      (crude rate per 100 000 person-years = 1457.1). The exposed group contributed 4
      011 264 person-years of follow-up, with 56 060 cancer diagnoses (crude rate per
      100 000 person-years = 1397.6). Exposure, compared with nonexposure, was
      associated with a statistically significantly increased risk for all-site cancer
      for all birth cohorts and for both sexes. The strongest associations between
      exposure and all-site cancer risk were observed in the youngest birth cohort of
      1940-1945 (for men, RR = 3.50, 95% CI = 2.17 to 5.65; for women, RR = 2.33, 95%
      CI = 1.69 to 3.21). Excess risk was pronounced for breast cancer in the 1940-1945
      birth cohort (RR = 2.44, 95% CI = 1.46 to 4.06) and for colorectal cancer in the
      1935-1939 cohort (for men, RR = 1.75, 95% CI = 1.19 to 2.59; for women, RR =
      1.93, 95% CI = 1.25 to 3.00). CONCLUSIONS: Incidence of all cancers, particularly
      breast and colorectal cancer, was higher among Israeli Jews who were potentially
      exposed to the Holocaust than among those who were not.

PMID- 19861306
TI  - Re: Cost-effectiveness analysis of human papillomavirus vaccination in the
      Netherlands.

PMID- 19861307
TI  - Dying by the way you live: AIF vs. caspases in apoptosis of hypertrophied
      cardiomyocytes.

PMID- 19861309
TI  - Cx30 in the sinus node of murine heart: just one connexin more, or more? Evidence
      for a construction principle?

PMID- 19861308
TI  - 17beta-Estradiol inhibits matrix metalloproteinase-2 transcription via MAP kinase
      in fibroblasts.
AB  - AIMS: Female sex and sex hormones contribute to cardiac remodelling. 17beta
      estradiol (E2) is involved in the modulation of extracellular matrix composition
      and function. Here, we analysed the effect of E2 on matrix metalloproteinase
      (MMP)-2 gene expression and studied the underlying molecular mechanisms in rat
      cardiac fibroblasts and in a human fibroblast cell line. METHODS AND RESULTS: In
      adult rat cardiac fibroblasts, E2 significantly decreased MMP-2 gene expression
      in an estrogen receptor (ER)-dependent manner. Transient transfection experiments
      of human MMP-2 (hMMP-2) promoter deletion constructs in a human fibroblast cell
      line revealed a regulatory region between -324 and -260 bp that is involved in
      E2/ERalpha-mediated repression of hMMP-2 gene transcription. Electrophoretic
      mobility shift assays (EMSA) and supershift analysis demonstrated the binding of
      transcription factor Elk-1 within this promoter region. Elk-1 was phosphorylated
      by E2 via the mitogen-activated protein kinase (MAPK) signalling pathway as shown
      by western blotting. Treatment of cells with the MAPK inhibitor PD98059 blocked
      the E2-dependent repression of hMMP-2 promoter activity as well as the endogenous
      MMP-2 mRNA levels in both human fibroblast cells and rat cardiac fibroblasts.
      CONCLUSION: E2 inhibits MMP-2 expression via the ER and the MAPK pathway in rat
      cardiac fibroblasts and in a human fibroblast cell line. These mechanisms may
      contribute to sex-specific differences in fibrotic processes that are observed in
      human heart and other diseases.

PMID- 19861310
TI  - Tubulin polymerization modifies cardiac sodium channel expression and gating.
AB  - AIMS: Treatment with the anticancer drug taxol (TXL), which polymerizes the
      cytoskeleton protein tubulin, may evoke cardiac arrhythmias based on reduced
      human cardiac sodium channel (Na(v)1.5) function. Therefore, we investigated
      whether enhanced tubulin polymerization by TXL affects Na(v)1.5 function and
      expression and whether these effects are beta1-subunit-mediated. METHODS AND
      RESULTS: Human embryonic kidney (HEK293) cells, transfected with SCN5A cDNA alone
      (Na(v)1.5) or together with SCN1B cDNA (Na(v)1.5 + beta1), and neonatal rat
      cardiomyocytes (NRCs) were incubated in the presence and in the absence of 100
      microM TXL. Sodium current (I(Na)) characteristics were studied using patch-clamp
      techniques. Na(v)1.5 membrane expression was determined by immunocytochemistry
      and confocal microscopy. Pre-treatment with TXL reduced peak I(Na) amplitude
      nearly two-fold in both Na(v)1.5 and Na(v)1.5 + beta1, as well as in NRCs,
      compared with untreated cells. Accordingly, HEK293 cells and NRCs stained with
      anti-Na(v)1.5 antibody revealed a reduced membrane-labelling intensity in the TXL
      treated groups. In addition, TXL accelerated I(Na) decay of Na(v)1.5 + beta1,
      whereas I(Na) decay of Na(v)1.5 remained unaltered. Finally, TXL reduced the
      fraction of channels that slow inactivated from 31% to 18%, and increased the
      time constant of slow inactivation by two-fold in Na(v)1.5. Conversely, slow
      inactivation properties of Na(v)1.5 + beta1 were unchanged by TXL. CONCLUSION:
      Enhanced tubulin polymerization reduces sarcolemmal Na(v)1.5 expression and I(Na)
      amplitude in a beta1-subunit-independent fashion and causes I(Na) fast and slow
      inactivation impairment in a beta1-subunit-dependent way. These changes may
      underlie conduction-slowing-dependent cardiac arrhythmias under conditions of
      enhanced tubulin polymerization, e.g. TXL treatment and heart failure.

PMID- 19861311
TI  - Multipotent mesenchymal stromal cell therapy in renal disease and kidney
      transplantation.
AB  - Cell therapies aim at differentiation of stem cells into the specific cell type
      required to repair damaged or destroyed cells or tissues. Over recent years, cell
      therapy has been introduced in a variety of application areas, including
      cardiovascular repair, diabetes, musculoskeletal disorders and renal repair.
      Multipotent mesenchymal stromal cells (MSCs), often referred to as mesenchymal
      stem cells, are of particular interest as a cell therapy model, as this is one of
      the few cell types that are on the brink of entering the clinical arena in
      different areas of application. MSCs can be differentiated in vitro and in vivo
      into various cell types of mesenchymal origin such as bone, fat and cartilage.
      They have important effects on the innate and adaptive immune system and possess
      striking anti-inflammatory properties that make them attractive for potential use
      in diseases characterized by autoimmunity and inflammation. In addition, MSCs
      have been shown to migrate to sites of tissue injury and to enhance repair by
      secreting anti-fibrotic and pro-angiogenic factors. In this review, evidence for
      the renoprotective mechanisms of MSCs as well as their therapeutic possibilities
      and potential hazards in acute and chronic renal disease and allograft rejection
      is summarized.

PMID- 19861312
TI  - The Danish Registry on Regular Dialysis and Transplantation: completeness and
      validity of incident patient registration.
AB  - BACKGROUND: The Danish National Registry on Regular Dialysis and Transplantation
      (NRDT) provides systematic information on the epidemiology and treatment of end
      stage chronic kidney disease in Denmark. It is therefore of major importance that
      the registry is valid and complete. The aim of the present study was to evaluate
      the registration of incident patients on chronic renal replacement therapy (RRT).
      METHODS: Incident patients on chronic RRT in the period 2001-2004 were identified
      in NRDT and in the National Patient Registry, which contains information on
      hospital admissions and treatments. In the National Patient Registry,
      identification of patients was as follows: patients receiving the procedure of
      dialysis during a minimum of 90 days and for a minimum of 12 times or the
      procedure of renal transplantation. Only patients with at least 2 years of
      dialysis-free interval before and never being transplanted were included. The
      completeness of NRDT was calculated as the percentage of new patients on chronic
      RRT registered in the National Patient Registry also found in NRDT. Validity of
      data in NRDT was assessed by information from medical records and analysed using
      kappa statistics. RESULTS: Completeness of NRDT: Of 3020 patients registered in
      the National Patient Registry as incident chronic RRT patients, 97.2% were found
      in NRDT but 22.5% with another year of entry. There were no differences in
      completeness between hospitals or regions. Validity of NRDT: Validity of common
      renal diagnoses and RRT modality was high: diabetic nephropathy (kappa = 0.98),
      adult polycystic kidney disease (kappa = 0.95), chronic glomerulonephritis (kappa
      = 0.78) and RRT modality (kappa = 0.94). The diagnosis CKD of unknown aetiology
      and type of diabetes were less valid (kappa = 0.62, 0.60 and 0.73, respectively).
      The date of RRT start had also high validity. CONCLUSIONS: Completeness of
      incident patient registration in NRDT was highly acceptable. Validity of incident
      patient data was also good, except for type of diabetes.

PMID- 19861313
TI  - Regulation of adenosine system at the onset of peritonitis.
AB  - BACKGROUND: Adenosine, a potent regulator of inflammation, is produced under
      stressful conditions due to degradation of ATP/ADP by the ectoenzymes CD39 and
      CD73. Adenosine is rapidly degraded by adenosine deaminase (ADA) or
      phosphorylated in the cell by adenosine kinase (AK). From four known receptors to
      adenosine, A(1) (A(1)R) promotes inflammation by a G(i)-coupled receptor. We have
      previously shown that A(1)R is up-regulated in the first hours following
      bacterial inoculation. The aim of the current study is to characterize the
      inflammatory mediators that regulate adenosine-metabolizing enzymes and A(1)R at
      the onset of peritonitis. METHODS: Peritonitis was induced in CD1 mice by
      intraperitoneal injection of Escherichia coli. TNFalpha and IL-6 levels were
      determined in peritoneal fluid by enzyme-linked immunosorbent assay. Adenosine
      metabolizing enzymes and the A(1)R mRNA or protein levels were analyzed by
      quantitative PCR or by Western blot analysis, respectively. RESULTS: We found
      that CD39 and CD73 were up-regulated in response to bacterial stimuli (6-fold the
      basal levels), while AK and ADA mRNA levels were down-regulated. Cytokine
      production and leukocyte recruitment were enhanced (2.5-fold) by treatment with
      an A(1)R agonist (2-chloro-N(6)-cyclopentyladenosine, 0.1 mg/kg) and reduced (2.5
      3-fold) by the A(1)R antagonist (8-cyclopentyl-1, 3-dipropylxanthine, 1 mg/kg).
      In contrast to lipopolysaccharide, IL-1, TNF and IFNgamma, only low IL-6 levels
      (0.01 ng/ml), in the presence of its soluble IL-6R (sIL-6R), were found to
      promote A(1)R expression on mesothelial cells. In mice, administration of
      neutralizing antibody to IL-6R or soluble gp130-Fc (sgp130-Fc) blocked peritoneal
      A(1)R up-regulation following inoculation. CONCLUSION: Bacterial products induce
      the production of adenosine by up-regulation of CD39 and CD73. Low IL-6-sIL-6R up
      regulates the A(1)R to promote efficient inflammatory response against invading
      microorganisms.

PMID- 19861314
TI  - Functional polymorphisms in transforming growth factor-beta-1 (TGFbeta-1) and
      vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal
      scarring following childhood urinary tract infection.
AB  - BACKGROUND: The risk of renal scar formation following urinary tract infection
      (UTI) varies markedly between individuals. We sought to investigate a possible
      role of the common polymorphisms in the gene encoding for VEGF and TGFbeta-1, key
      regulators of tissue repair, in renal scarring. METHODS: Acute pyelonephritis was
      diagnosed in 104 children (63 males) aged 2 months to 12 years by urine culture
      and 99Tc-DMSA renal scan. A follow-up isotope scan was performed 4-6 months later
      to identify new renal scar formation. Vesicoureteral reflux (VUR) was examined by
      micturating cystourethrogram. Controls comprised 300 healthy children with no
      evidence of renal disease. Three single-nucleotide polymorphisms (SNPs) in the
      TGFbeta-1 (-800 A/G, -509 C/T and 869 C/T) and four SNPs in the VEGF gene (-2578
      C/A, -1154 G/A, -460 T/C and +405 G/C) were genotyped in all subjects. RESULTS:
      Forty-six of the 104 patients developed renal parenchymal scarring (44.2%). VUR
      was found in 35.6%. The -509 T allele in the TGFbeta-1 promoter was significantly
      more common in cases with renal scarring (51%) than in non-scarring patients
      (22.4%) and controls (23.6%) (both P < 0.0001). At the haplotype level, the GTC
      combination at -800/-509/+869 was strongly associated with renal scarring (P =
      0.0002). VEGF-460 CC was more common in UTI cases with renal scarring than in non
      scarring patients and controls (P = 0.03 and 0.001, respectively). Multiple
      logistic regression testing identified the presence of VUR (odds ratio 12.4, CI
      3.8-40; P < 0.001) and the TGFbeta-1 -509 T allele (OR 6.1, CI 2.4-15.5; P <
      0.001) as independent risk factors for renal scarring after UTI. In contrast,
      age, gender and the type of underlying organism were not predictive of renal
      scarring. CONCLUSIONS: Activating variants in the TGFbeta-1 and VEGF gene
      promoters are associated with post-UTI renal scar formation in children. The
      TGFbeta-1 509T allele predicts renal scarring independent of VUR.

PMID- 19861315
TI  - The first Chinese Pierson syndrome with novel mutations in LAMB2.
AB  - BACKGROUND: Pierson syndrome is typically manifested with congenital nephrotic
      syndrome (CNS) and peculiar ocular changes. LAMB2 was the causative gene.
      METHODS: A 3.25-year-old girl presenting with childhood-onset heavy proteinuria,
      bilateral myosis and nystagmus was detected on mutations of LAMB2 gene by PCR
      direct sequencing. RESULTS: Two novel mutations were identified, C757fsX767 and
      P1413fsX1451, which predicted truncated proteins and were confirmed in the
      paternal and maternal origins, respectively. CONCLUSIONS: This is the first
      Chinese case of Pierson syndrome diagnosed by clinical manifestations and LAMB2
      gene mutations. The phenotype may be different in different ethics.

PMID- 19861316
TI  - Quartan malaria-associated childhood nephrotic syndrome: now a rare clinical
      entity in malaria endemic Nigeria.
AB  - BACKGROUND: The study determined (i) whether or not quartan malaria nephropathy
      (QMN) is still a major cause of childhood nephrotic syndrome (CNS) in Nigeria,
      (ii) secondary causes other than QMN and their associated glomerular pathology
      and (iii) renal and patient outcome. METHODS: The study was a prospective non
      randomized study of consecutive cases of secondary CNS. Patients with idiopathic
      CNS were excluded. RESULTS: Twenty-four of 78 (30.8%) CNS cases were of secondary
      aetiology. Overall mean ages at onset of secondary CNS aetiology and CNS onset
      were 8.97 +/- 3.59 (1-15.3) and 9.95 +/- 3.15 (5-15.3) years, respectively. Male
      (14)/female (10) ratio was 1.4. Secondary causes comprised systemic lupus
      erythematosus (SLE, 37.5%), sickle cell anaemia (SCA, 16.7%), hepatitis B virus
      (HBV, 16.7%) infection, Churg-Strauss syndrome (12.6%), SLE/human
      immunodeficiency virus infection (4.2%), rhabdomyosarcoma (4.2%), bee stings
      (4.2%) and Addison's disease (4.2%). The overall cumulative complete remission
      (CR) rate was 88.0%. Remission was sustained in 11 of 16 (68.8%) CR patients,
      while one patient (6.25%) relapsed; the remaining four patients (24.95%) were yet
      to attain sustained remission. Median relapse-free period was 10.5 (0.75-25)
      months. Cumulative renal survival was 75.2% at 3 years. Three patients were lost
      to follow-up, while two died. Overall cumulative patient survival probability at
      36 months was 90.8%. All patients were followed for a median period of 12.5 (0.11
      36.0) months. CONCLUSION: Overall outcome of CNS has improved significantly
      compared to the 1960s and 1970s when the poor outcome of QMN was the predominant
      glomerular lesion in Nigeria. While quartan malaria-associated nephrotic syndrome
      has become a rare clinical entity, SLE, SCA and HBV infection have become the
      major secondary aetiologies of CNS in Nigeria.

PMID- 19861317
TI  - The spindle pole body of the pathogenic yeast Cryptococcus neoformans: variation
      in morphology and positional relationship with the nucleolus and the bud in
      interphase cells.
AB  - The spindle pole body (SPB) in the interphase cell of the pathogenic yeast
      Cryptococcus neoformans was studied in detail by freeze-substitution and serial
      ultrathin sectioning electron microscopy. The SPB was located on the outer
      nuclear envelope and appeared either dumbbell- or bar shaped. The dumbbell-shaped
      SPBs were 228-365 nm long with amorphous spheres on each end, each sphere being
      78-157 nm in diameter. The bar-shaped SPBs were 103-260 nm long and 32-113 nm
      thick. They consisted of filamentous materials. The dumbbell-shaped SPBs were
      more frequent (61%) than the bar-shaped SPBs. The bar-shaped SPBs may be regarded
      as dumbbell-shaped SPBs whose spherical parts became sufficiently small. There
      seemed to be no relationship between the SPB shape and the cell cycle stage of G1
      G2, since both types of SPB appeared not only in unbudded cells but also in
      budded cells and their appearance seems to be random. It is not clear at present
      whether morphological changes between dumbbell- and bar shapes have any
      physiological function. The SPB tended to be localized away from the nucleolus
      (141 degrees +/- 44 degrees), but localized randomly to the bud (97 degrees +/-
      50 degrees). The present study highlights the necessity of observing a large
      number of micrographs in three dimensions to describe accurately the
      ultrastructure of the SPB in yeast.

PMID- 19861318
TI  - Gender differences in age, period, and birth-cohort effects on the suicide
      mortality rate in Japan, 1985-2006.
AB  - Because suicide is increasingly becoming a public health threat in Japan, it is
      necessary to identify high-risk groups to develop effective preventive measures.
      The suicide mortality trends from 1985 to 2006 for Japanese aged between 15 and
      79 years were analyzed by a Bayesian age-period-cohort analysis to evaluate the
      independent effects of age, period, and birth cohort. Age-specific effect showed
      an overall increase with age in both genders, but a distinct increase was noted
      only among men aged between 50 and 64 years. The period effect exhibited a sudden
      rise in 1998; this effect was more apparent in men than in women. The cohort
      specific effect increased in male birth cohorts born after 1926 and in female
      birth cohorts born after 1956. In conclusion, a gender difference was detected in
      the effects of age, period, and cohort on suicide risk among Japanese.

PMID- 19861319
TI  - Self-injurious behavior in correctional settings.
AB  - This article reviews the literature concerning self-injury among criminal
      offenders. It describes many of the problems, barriers, and obstacles to
      effective assessment and treatment of self-injury and discusses the absence of a
      clear paradigm within which to develop a classification system and standardized
      nomenclature to describe the spectrum of self-injurious behaviors. This article
      distinguishes between self-injury resulting from suicidal versus nonsuicidal
      intent, presents treatment strategies for managing each, and concludes with a
      proposed set of eight recommended goals for creating a national strategy to
      develop self-injury programming in correctional settings.

PMID- 19861320
TI  - Development and evaluation of a psychometric instrument designed to assess HIV
      risk behaviors of prison inmates.
AB  - Clinicians and researchers interested in HIV interventions for prisoners lack an
      appropriate psychometric instrument to assess HIV risk behaviors. This study
      evaluated the readability and internal consistency of a questionnaire designed to
      assess such behaviors. The questionnaire was administered to 277 inmates. The
      Flesch Reading Ease score was 78.3 with a Flesch-Kincaid grade level of 3.7,
      suggesting limited comprehension difficulties. Internal consistency was evaluated
      by determining Cronbach's alpha (Calpha) for total items and for each subscale.
      Following factor analyses, 25 items converged into five subscales and combined
      they account for 72% of the variance. The overall Calpha was .86 and the
      subscales Calpha ranged from .82 to .98. Findings reveal that the questionnaire
      is internally consistent and suitable for use with prisoners with low literacy
      skills. The use of this instrument for intervention studies in prisons has the
      potential to reduce inmates' HIV risk behaviors.

PMID- 19861322
TI  - T-wave inversions in elite athletes: the best predictors have yet to be
      determined.

PMID- 19861321
TI  - Barriers and facilitators: parolees' perceptions of community health care.
AB  - Paroled individuals have physical and mental health problems and addiction
      disorders at rates greater than the general population. The aim of this study was
      to identify the perceived barriers and facilitators parolees encounter in their
      efforts to access and utilize health care services in the community. Qualitative
      data were collected via individual interviews with 17 chronically ill, middle
      aged male parolees. Study results included financial and administrative barriers
      to care; structural facilitators to care; and the influence of clinicians'
      professional demeanor on health care access. Increased access to health care can
      provide opportunities to address both the health care and reintegration needs of
      individuals on parole.

PMID- 19861323
TI  - Not too late, not too fast!!

PMID- 19861324
TI  - Carotid artery stenting vs. endarterectomy.
AB  - Randomized clinical trials have demonstrated that carotid endarterectomy (CEA) is
      superior to medical management for stroke prevention in patients with symptomatic
      and, to a lesser degree, asymptomatic internal carotid artery stenosis. However,
      large-scale registries have shown that the adverse event rates following CEA are
      commonly higher than observed in the trials. In the last decade, carotid artery
      stenting (CAS) has emerged as a less invasive alternative to surgery. In order to
      address the efficacy of CAS, we performed a meta-analysis of 10 randomized trials
      comparing CAS with CEA in 4648 mainly symptomatic patients. The analysis showed
      that CAS was associated with a statistically significant increased death or
      stroke rate at 30 days compared with CEA (odds ratio 1.60, 95% confidence
      interval 1.26-2.02). However, most of the trials had inadequate requirements in
      terms of endovascular expertise and did not mandate the use of emboli protection
      devices. Beyond 30 days, long-term follow-up of the trials previously reported
      suggest that both revascularization techniques are equivalent in terms of stroke
      prevention. Conversely, large-scale high-quality CAS registries--mostly with
      independent neurological assessment and clinical event committee adjudication-
      have reported results in the range of current recommendation for CEA in over 20
      000 patients, despite the fact that the majority of patients were at high risk
      for surgery. Until further data become available, the performance of CAS should
      be limited to protocols or centres of excellence and targeted especially to
      patients at high risk for surgery.

PMID- 19861325
TI  - Minimally invasive video-assisted approach for left atrial myxoma resection.
AB  - Minimally invasive surgery has become the standard approach for several cardiac
      diseases. We report in the present study our ten-year experience with endoscopic
      cardiac surgery for left atrial myxoma resection. Between January 1998 and
      January 2008, 14 patients (median age: 61 years) underwent surgery for left
      atrial myxoma resection at our institution. The Heartport access system and the
      video-assistance were systematically employed to provide excellent vision and
      facilitate surgery. The aortic clamping was obtained with an 'EndoClamp' in 11
      cases (using a central or peripheral endoaortic balloon, depending on the site of
      the arterial cannulation) or transthoracically with the Portaclamp system in two
      cases and the Chitwood clamp in one case. The average time needed for cross
      clamping was 49+/-29 min, with a mean cardiopulmonary bypass (CPB) time of 88+/
      57 min. There were no early or late hospital deaths. Mean intensive care unit and
      hospital stay were three and eight days, respectively. The mean follow-up time
      was 64 months and there was no evidence of residual or recurrent tumor. There
      were two late deaths due to acute ischemic stroke. Minimally invasive video
      assisted surgery for left atrial myxoma resection is a safe, reproducible and
      cosmetic operation and can be considered an effective oncologic approach as an
      alternative to standard sternotomy.

PMID- 19861326
TI  - Comprehensive approach for clamping severely calcified ascending aorta using
      computed tomography.
AB  - A severely calcified ascending aorta is generally considered unclampable. Many
      surgeons have developed procedures to avoid manipulation such as cross-clamping
      on such calcified aorta. However, these alternatives are sometimes complicated
      and require a more invasive procedure than the conventional method. We assessed
      our comprehensive strategy for clamping of a severely calcified aorta using
      preoperative computed tomography (CT). We found that the extent of calcification
      just below the innominate artery was significantly less than that at the usual
      ascending aorta clamp site. After confirming that the extent of calcification
      just below the innominate artery was <75% of the entire circumference by
      preoperative CT, ascending aorta was clamped with a soft cross-clamp placed on
      the ascending aorta with particular care to orientate the clamp parallel to the
      calcification. All operations were completed under usual cardiopulmonary bypass
      with mild hypothermia. All patients survived surgery and no patients had a
      postoperative neurological complication. Our results provide important
      information for the management of these high-risk patients, with a comprehensive
      approach used to choose the appropriate option for an optimal outcome.

PMID- 19861327
TI  - Estrogen receptor {alpha} gene polymorphisms in patients with idiopathic
      premature ovarian failure.
AB  - BACKGROUND: It has been reported that polymorphisms in the estrogen receptor (ER)
      alpha gene (ESR1) may be associated with reproductive patterns of women. This
      study was performed to investigate whether the genetic polymorphisms of the ER
      alpha gene are associated with idiopathic premature ovarian failure (POF) in a
      Korean population. METHODS: The subjects were 126 idiopathic POF patients and 221
      post-menopausal controls recruited from university hospitals between 1999 and
      2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were
      deduced by using the Haploview version 4.1. Bonferroni correction was applied for
      the correction of multiple testing. RESULTS: There was no significant difference
      in the allele distribution of the ER-alpha gene (TA)n repeats between the POF and
      the control group. For the PvuII polymorphism, the POF group showed a higher
      frequency of TT genotype compared with the controls (41.3 versus 26.3%, P =
      0.004, 98.75% CI 1.8-28.2%). No significant difference was found in the
      distribution of the XbaI polymorphism between the POF and the control group.
      Haplotype analysis showed that the frequency of TA haplotype was significantly
      higher in the POF patients compared with the controls (64.7 versus 52.7%, P =
      0.002, 98.75% CI 2.4-21.6%). CONCLUSIONS: These findings suggest that the ER
      alpha gene polymorphisms may be associated with idiopathic POF.

PMID- 19861329
TI  - Weaknesses, strengths and needs in fertility care according to patients.
AB  - BACKGROUND: The patients' role in assessing health care quality is increasingly
      recognized. Measuring patients' specific experiences and needs generates concrete
      information for care improvement, whereas satisfaction surveys only give an
      overoptimistic, undifferentiating picture. Therefore, this study aimed to
      investigate possible weaknesses, strengths and needs in fertility care by
      measuring patients' specific experiences. METHODS: Mixed (qualitative and
      quantitative) methods were used to identify weaknesses, strengths and needs in
      fertility care. Four focus groups with 21 infertile patients were used for
      documenting care aspects relevant to patients. The fully transcribed qualitative
      results were analysed and converted into a 124-item questionnaire, to investigate
      whether these aspects were regarded as weaknesses, strengths or needs in
      fertility care. The questionnaire was distributed to 369 eligible couples
      attending 13 Dutch fertility clinics. Descriptive statistics were used to
      determine the quantity of the weaknesses, strengths and needs. RESULTS: Overall,
      286 women (78%) and 280 men (76%) completed the questionnaire. Patients
      experienced many weaknesses in fertility care, mostly regarding emotional support
      and continuity of care. Respect and autonomy and partner involvement were
      considered strengths in current care. Furthermore, women expressed their need for
      more doctors' continuity during their treatment, and couples strongly desired to
      have free access to their own medical record. The questionnaire's internal
      consistency and construct validity were sufficient. CONCLUSIONS: Infertile
      couples experience strengths, but also many weaknesses and needs in current
      fertility care. Lack of patient centredness seems to be a major cause herein.
      Using mixed methods is a sensitive means for identifying these weaknesses and
      needs.

PMID- 19861328
TI  - Embryo development of fresh 'versus' vitrified metaphase II oocytes after ICSI: a
      prospective randomized sibling-oocyte study.
AB  - BACKGROUND: A successful oocyte cryopreservation programme is of utmost
      importance where a limited number of oocytes can be inseminated per cycle, to
      overcome legal and ethical issues related to embryo storage, for oocyte donation
      programmes and for fertility preservation (especially for cancer patients).
      Vitrification has been recently proposed as an effective procedure for this
      purpose. METHODS: In order to validate the effectiveness of oocyte vitrification
      a non-inferiority trial was started on sibling metaphase II (MII) oocytes. To
      demonstrate the non-inferiority based on an absolute difference of 17% in the
      fertilization rate per sibling oocyte, a minimum of 222 oocytes were required.
      After oocyte denudation, MII oocytes with normal morphology were randomly
      allocated to fresh ICSI insemination or to vitrification procedure. If pregnancy
      was not obtained a subsequent ICSI cycle was performed with warmed oocytes of the
      same cohort. In both groups, three oocytes were inseminated per cycle by ICSI
      procedure. Primary end-points were fertilization rates calculated per warmed and
      per injected oocytes. Secondary end-points were zygote and embryo morphology.
      RESULTS: A total of 244 oocytes were involved in this study. Of the 120 fresh
      sibling oocytes inseminated, 100 were fertilized (83.3%). Survival rate of
      sibling vitrified oocytes was 96.8% (120/124 oocytes). Fertilization rate after
      ICSI was 76.6% (95/124) per warmed oocyte and 79.2% (95/120) per
      survived/inseminated oocyte. No statistical difference in fertilization rates was
      observed between the two groups when calculated per sibling oocytes (absolute
      difference -6.73%; OR: 0.65; 95% CI = 0.33-1.29; P = 0.20) and per inseminated
      oocyte (absolute difference -4.17%; OR: 0.76; 95% CI = 0.37-1.53; P = 0.50).
      Embryo development was also similar in both treatment groups up till Day 2. The
      percentage of excellent quality embryos was 52.0% (52/100) in the fresh group and
      51.6% (49/95) in the vitrification group (absolute difference -0.43%; OR: 0.98;
      95% CI = 0.53-1.79; P = 0.9). The mean age of the 40 patients included in this
      study was 35.5 +/- 4.8 years (range 26-42). Fifteen clinical pregnancies were
      obtained in the vitrification cycles of 39 embryo transfers performed (37.5% per
      cycle, 38.5% per embryo transfer), with an implantation rate of 20.2% (19/94).
      Three spontaneous miscarriages occurred (20%). Twelve pregnancies are ongoing
      (30.0% per cycle, 30.8% per embryo transfer) beyond 12 weeks of gestation.
      CONCLUSIONS: Our results indicate that oocyte vitrification procedure followed by
      ICSI is not inferior to fresh insemination procedure, with regard to
      fertilization and embryo developmental rates. Moreover, ongoing clinical
      pregnancy is compatible with this procedure, even with a restricted number of
      oocytes available for insemination. The promising clinical results obtained, in a
      population of infertile patients, need to be confirmed on a larger scale.
      CLINICAL TRIALS REGISTRATION NUMBER: iSRCTN60158641.

PMID- 19861330
TI  - An experimental protocol for fertility preservation in prepubertal boys recently
      diagnosed with cancer: a report of acceptability and safety.
AB  - BACKGROUND: Gonadal damage is a consequence of therapy for pediatric
      malignancies. Prepubertal males have no semen or mature spermatozoa, posing a
      challenge for fertility preservation. Testicular tissue cryopreservation is a
      potential option but is still experimental. We report on a pilot protocol that
      offered testicular biopsy cryopreservation to families of prepubertal boys with
      newly diagnosed malignancy. The aims were to determine the acceptability and
      safety of this procedure. METHODS: Parents of prepubertal boys with diagnoses at
      highest risk for treatment-related gonadal damage were offered the option of
      testicular cryopreservation. Half of the biopsy was frozen for the subject's
      potential future use and the remainder used for research. Data on negative
      intraoperative and/or 7 day post-operative sequelae of testicular biopsies were
      assessed. Two to four weeks later, parents were asked to complete a questionnaire
      on factors influencing their decision to have the biopsy or not. RESULTS: Since
      January 2008, 24 boys have met the eligibility criteria but three required
      immediate treatment and were excluded. Sixteen of 21 families (76%) consented to
      testicular biopsy, indicating the prospective acceptability of this option to
      parents of boys aged 3 months to 14 years; 14 underwent the procedure without any
      negative intra- or post-operative sequelae. Although the time at diagnosis is
      stressful, families can give thoughtful consideration to this option. Factors
      such as religion, finance, ethics and the experimental nature of cryopreservation
      did not play a major role in decision-making. CONCLUSIONS: Parents of prepubertal
      boys with cancer are willing to pursue testicular tissue cryopreservation at
      diagnosis, and testicular biopsy caused no acute adverse effects.

PMID- 19861331
TI  - Clinical evaluation of the mini-mental state exam with culturally deaf senior
      citizens.
AB  - The Mini-Mental State Exam (MMSE) is commonly used to screen cognitive function
      in a clinical setting. The measure has been published in over 50 languages;
      however, the validity and reliability of the MMSE has yet to be assessed with the
      culturally Deaf elderly population. Participants consisted of 117 Deaf senior
      citizens, aged 55-89 (M = 69.44, SD = 8.55). Demographic information, including
      state of residence, age, and history of depression, head injury, and dementia
      diagnoses, were collected. A standard form of the MMSE was used with modification
      of test administration and stimuli including translation of English test items
      into a sign-based form and alteration of two items in order to make them
      culturally and linguistically appropriate. Significant correlations were observed
      between overall test score and education level (r = .23, p = .01) as well as test
      score and age (r = -.33, p < .001). Patterns of responses were analyzed and
      revealed several items that were problematic and yielded a fewer correct
      responses. These results indicate that clinicians need to be aware of cultural
      and linguistic factors associated with the deaf population that may impact test
      performance and clinical interpretation of test results. On the basis of these
      data, there is an increased risk of false positives obtained when using this
      measure. Further research is needed to validate the use of this measure with the
      culturally Deaf population.

PMID- 19861332
TI  - Heparin's 'potential to improve pregnancy rates and outcomes' is not evidence
      based.

PMID- 19861334
TI  - Combination testing of multidrug-resistant cystic fibrosis isolates of
      Pseudomonas aeruginosa: use of a new parameter, the susceptible breakpoint index.
AB  - OBJECTIVES: The microbiology laboratory at Aberdeen Royal Infirmary operates an
      extended susceptibility testing service for multidrug-resistant Gram-negative non
      fermenting isolates from the sputum of Scottish cystic fibrosis patients. The
      service aims to provide clinicians with useful treatment options and developed
      the use of a novel parameter-the susceptible breakpoint index (SBPI), which
      allows easy ranking of the antimicrobial combinations in order of their possible
      in vivo effectiveness. METHODS: Three hundred and fifteen isolates of Pseudomonas
      aeruginosa were submitted for testing. MICs of 14 antimicrobials were determined
      using the Etest and the results categorized using CLSI guidelines. Usually, six
      antimicrobial pairs were tested in combination also using the Etest. The results
      were assessed using the fractional inhibitory concentration index (FICI) and also
      by a novel parameter, the SBPI. RESULTS: Some 4173 MICs and 1663 combination
      pairs were performed. The most active individual antimicrobials were colistin,
      tobramycin and amikacin, with 84%, 69% and 32% of isolates susceptible,
      respectively. Twenty-eight of 44 antimicrobial combinations were tested >10
      times. Of the combinations, 3.6% were synergistic (FICI < or = 0.5) and 0.1% were
      antagonistic (FICI > 4.0). Amikacin + ceftazidime (17%), ciprofloxacin +
      ceftazidime (12.9%) and ciprofloxacin + piperacillin/tazobactam (12%) were the
      most synergistic combinations. By median SBPI, the most effective combinations in
      vitro were colistin + ticarcillin/clavulanate, colistin + piperacillin/tazobactam
      and colistin + meropenem. CONCLUSIONS: The Etest is a useful tool for determining
      MICs and testing antimicrobial combinations. The SBPI is more discriminatory than
      the FICI, allowing easy ranking of the combinations, and is likely to have
      clinical relevance.

PMID- 19861335
TI  - Enhancing antibiotic activity: a strategy to control Acinetobacter infections.
AB  - OBJECTIVES: The emergence of antibiotic resistance has seriously diminished
      antibiotic efficacy and an increasing number of infections are becoming difficult
      to treat. One approach to the restoration of antibiotic activity is to administer
      them in conjunction with non-antibiotic compounds that depress resistance
      mechanisms. We describe the activity of ellagic and tannic acids as adjuvants
      that enhance the activity of aminocoumarin antibiotics against multidrug
      resistant (MDR) Acinetobacter baumannii. METHODS: Adjuvant activity of plant
      phenolics was tested using growth inhibition assays in combination with
      subinhibitory concentrations of novobiocin. The antibacterial susceptibilities of
      susceptible and MDR A. baumannii to a variety of antibiotics were determined in
      the absence and presence of ellagic and tannic acids. The effect of the adjuvants
      on bacterial outer membrane function was examined by using the fluorescence dye 1
      N-phenylnaphthylamine (NPN). The efflux pump inhibition was measured by the
      intracellular accumulation of ethidium bromide (EtBr) and pyronin Y. RESULTS: At
      40 microM, ellagic and tannic acids enhanced the activity of novobiocin,
      coumermycin, chlorobiocin, rifampicin and fusidic acid against A. baumannii.
      There were no increases in the uptake of NPN or in the accumulation of EtBr after
      strains were treated with these adjuvants; however, the intracellular
      accumulation of pyronin Y by the treated cells was significantly increased,
      suggesting that ellagic and tannic acids act as efflux pump inhibitors.
      CONCLUSIONS: Susceptibility of MDR A. baumannii to a variety of antibiotics was
      enhanced in the presence of ellagic and tannic acids. The use of such plant
      compounds might provide effective treatments for resistant Gram-negative
      bacterial infections.

PMID- 19861336
TI  - pSGI15, a small ColE-like qnrB19 plasmid of a Salmonella enterica serovar
      Typhimurium strain carrying Salmonella genomic island 1 (SGI1).

PMID- 19861337
TI  - Limitations of antibiotic options for invasive infections caused by methicillin
      resistant Staphylococcus aureus: is combination therapy the answer?
AB  - Invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA),
      particularly those involving persistent bacteraemia, necrotizing pneumonia,
      osteomyelitis and other deep-seated sites of infections, are associated with high
      mortality and are often difficult to treat. The response to treatment of severe
      MRSA infection with currently available antibiotics active against MRSA is often
      unsatisfactory, leading some physicians to resort to combination antibiotic
      therapy. Now, with the emergence of community-associated MRSA (CA-MRSA) clones
      that display enhanced virulence potentially related to up-regulated toxin
      production, the use of adjuvant protein synthesis-inhibiting antibiotics to
      reduce toxin production also has been advocated by some experts. In this review,
      we discuss the limitations of antibiotics currently available for the treatment
      of serious invasive MRSA infections and review the existing literature that
      examines the potential role of combination therapy in these infections.

PMID- 19861338
TI  - Molecular screening for rifampicin and fluoroquinolone resistance in a clinical
      population of Brucella melitensis.
AB  - OBJECTIVES: The aim of this study was to determine, using molecular methods,
      whether rifampicin and fluoroquinolone resistance was present in a clinical
      Brucella melitensis population. METHODS: Sixty-two B. melitensis strains,
      isolated from humans-most experiencing their first brucellosis episode-over an 11
      year period in Spain, were genotyped by multiple locus variable analysis (MLVA
      16) for future studies. In the present work, molecular screening was undertaken
      to detect the presence of rpoB and gyrA/gyrB/parC/parE mutations (previously
      described in in vitro Brucella spp. mutants) related to resistance to rifampicin
      and fluoroquinolones, respectively. RESULTS: Sixty-two MLVA-16 genotypes were
      identified among the B. melitensis population, with genetic similarity values
      ranging from 32% to 94%. rpoB mutations related to rifampicin resistance
      (positions 154, 526, 536, 539, 541, 574) were not detected. Neither were changes
      in GyrA described in in vitro mutants (67, 71, 87, 91 and an insertion at 340)
      detected in these strains. All showed identical GyrA, GyrB, ParC and ParE
      sequences with respect to B. melitensis 16M, except for one strain (ciprofloxacin
      and moxifloxacin MICs 0.25-0.50 mg/L) that harboured the Val264Ala replacement
      outside the GyrA quinolone resistance-determining region (QRDR); no differences
      were seen, however, in the NorMI/II efflux pump genes. CONCLUSIONS: The absence
      of rpoB mutations clearly related to rifampicin resistance in clinical B.
      melitensis strains reinforces the first-choice status of this antibiotic in the
      treatment of first brucellosis episodes, and demonstrates the usefulness of
      molecular screening for resistant genotypes. The absence of topoisomerase II-IV
      mutations, however, cannot rule out fluoroquinolone resistance due to the
      interplay of different mechanisms.

PMID- 19861339
TI  - Treatment of acute hepatitis C in HIV infection.
AB  - Within Europe and recently in the USA and Australia an ongoing epidemic of acute
      hepatitis C virus (HCV) infections among HIV-positive individuals, mainly men who
      have sex with men, has been observed. Other concomitant sexually transmitted
      diseases and sexual practices with a high risk of mucosal trauma and damage have
      been established as risk factors for sexual transmission. In HIV-positive
      patients the diagnosis of acute HCV infection may be obscured by delayed anti-HCV
      antibody seroconversion, and HCV RNA testing may be warranted. It is estimated
      that up to 85% of HIV-positive patients take a chronic course after acute HCV
      infection, and early treatment of acute HCV infection within 12 weeks after the
      presumed date of infection is recommended unless spontaneous clearance of HCV has
      occurred. A watch and wait strategy for 4-8 weeks after the date of diagnosis
      with 4 weekly HCV RNA controls may help to distinguish patients who will
      spontaneously clear acute HCV infection from those who will not. Treatment of
      acute HCV infection with interferon-based therapy has been shown to be highly
      efficacious, with sustained virological response rates in between 60% and 70% of
      HIV-positive individuals. Though data are sparse, controlling treatment response
      at weeks 4 and 12 may further help to individualize therapy, and patients who
      have not reached a negative HCV RNA by week 12 may benefit from prolonged
      treatment beyond 24 weeks.

PMID- 19861340
TI  - Determinants of mental health stigma among pharmacy students in Australia,
      Belgium, Estonia, Finland, India and Latvia.
AB  - BACKGROUND: Healthcare professionals commonly exhibit negative attitudes toward
      people with mental disorders. Few international studies have sought to
      investigate the determinants of stigma. OBJECTIVE: To conduct an international
      comparison of pharmacy students' stigma towards people with schizophrenia, and to
      determine whether stigma is consistently associated with stereotypical attributes
      of people with schizophrenia. METHOD: Students (n = 649) at eight universities in
      Australia, Belgium, India, Finland, Estonia and Latvia completed a seven-item
      Social Distance Scale (SDS) and six items related to stereotypical attributes of
      people with schizophrenia. RESULTS: Mean SDS scores were 19.65 (+/- 3.97) in
      Australia, 19.61 (+/- 2.92) in Belgium, 18.75 (+/- 3.57) in India, 18.05 (+/-
      3.12) in Finland, and 20.90 (+/- 4.04) in Estonia and Latvia. Unpredictability
      was most strongly associated with having a high social distance in Australia
      (beta = -1.285), the perception that people will never recover in India (beta = -
      0.881), dangerousness in Finland (beta = -1.473) and the perception of being
      difficult to talk to in Estonia and Latvia (beta = -2.076). Unpredictability was
      associated with lower social distance in Belgium (beta = 0.839). CONCLUSION: The
      extent to which students held stigmatizing attitudes was similar in each country,
      however, the determinants of stigma were different. Pharmacy education may need
      to be tailored to address the determinants of stigma in each country.

PMID- 19861341
TI  - Hallucinations and related perceptual disturbance in a non-clinical Spanish
      population.
AB  - BACKGROUND: Several studies have suggested the continuity of psychotic symptoms
      between the general population and clinical samples, and have shown that, in
      fact, the predisposition to hallucinations is a multi-dimensional construct.
      However, there is no agreement concerning the number of factors comprising it or
      the significance of psychotic-like experiences. An examination of the beliefs
      associated with these experiences could increase knowledge of the continuity of
      hallucinations. AIMS: The purpose of this work was to analyze the structure of
      the Revized Hallucination Scale (RHS), applied to a sample of Spanish university
      students to find out the meaning for the participants and their associated
      beliefs on each item. METHODS: The RHS was administered to a total of 265
      participants. Along with the frequency of each experience, participants were
      asked to provide an example of each situation described and to what they
      attributed it. RESULTS: The results emphasized the presence of four factors that
      are variously made up of six types of beliefs: personal difficulties;
      psychological explanations; dreamlike experiences; vivid thoughts; perceptive
      distortions; and personal desires. CONCLUSIONS: The relevance of these results
      with regard to the differences that might exist in hallucinations in clinical and
      normal populations is discussed.

PMID- 19861343
TI  - Prognostically distinct clinical patterns of systemic lupus erythematosus
      identified by cluster analysis.
AB  - The objective of this study was to evaluate the patterns of clinical
      manifestations and their mortality in a large cohort of Chinese patients with
      systemic lupus erythematosus. The cumulative clinical manifestations of a large
      group of Chinese systemic lupus erythematosus patients who fulfilled at least
      four American College of Rheumatology criteria for systemic lupus erythematosus
      were studied. Patients were divided into distinct groups by using the K-mean
      cluster analysis. Clinical features, prevalence of proliferative lupus nephritis
      (World Health Organization class III, IV), autoantibody profile, and treatment
      data were compared and the standardized mortality ratios were calculated for each
      cluster of patients. There were 1082 patients included in the study (mean age at
      systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus
      erythematosus duration 10.3 years). Three distinct groups of patients were
      identified. Cluster 1 (n = 347) was characterized predominantly by mucocutaneous
      manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and
      arthritis but having the lowest prevalence of serositis, hematologic
      manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and
      proliferative lupus nephritis. Patients in cluster 2 (n = 409) had mainly renal
      and hematological manifestations but having the lowest prevalence of
      mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were
      significantly more frequent in cluster 2 than the other clusters. Cluster 3
      patients (n = 326) had the most heterogeneous features. Besides having a high
      prevalence of mucocutaneous manifestations, serositis and hematologic
      manifestations, renal involvement, and proliferative lupus nephritis was also
      most prevalent among the three clusters. Patients in cluster 2 had a much higher
      standardized mortality ratio [standardized mortality ratio 7.23 (6.7-7.7), p <
      0.001] than those in cluster 3 [standardized mortality ratio 1.27 (1.1-1.5), p =
      0.005] and cluster 1 [standardized mortality ratio 0.95 (0.5-1.7), p = 0.86]. In
      conclusion, patients with systemic lupus erythematosus could be clustered into
      prognostically distinct patterns of clinical manifestations.

PMID- 19861342
TI  - The relationship between race, cigarette smoking and carotid intimal medial
      thickness in systemic lupus erythematosus.
AB  - Racial differences are known to account for a higher incidence of systemic lupus
      erythematosus (SLE), as well as increased disease severity and mortality. The
      purpose of this study was to determine whether there are any race-specific risk
      factors that affect measures of subclinical atherosclerosis in SLE patients.
      Traditional and SLE-related cardiovascular disease (CVD) risk factors were
      assessed in 106 female SLE patients. Carotid medial intimal medial thickness
      (mIMT) and coronary artery calcification (CAC) were measured on all subjects.
      Differences were evaluated between races for all clinical, serologic, and CVD
      risk factors and the racial interactions with all covariables. Outcomes included
      mIMT and CAC. There were no significant differences between races with regard to
      mIMT or CAC. Significant covariables in the final model for mIMT included age,
      triglycerides, glucose, and race-age and race-smoking interactions. A prediction
      model with fixed significant covariables demonstrated that Black subjects with a
      smoking history had a significantly higher mIMT than Blacks who had never smoked,
      an effect not seen in Whites. There were no differences between having CAC or
      with the CAC scores between the races. In the final model for CAC, age and SLE
      disease duration were significant covariables impacting CAC. When controlling for
      other significant CVD covariables and interactions, Black women, but not White,
      with SLE with a history of smoking have higher mIMT measurements than those who
      have never smoked. This is the first report documenting the race-specific effect
      of smoking on subclinical measures of CVD in SLE.

PMID- 19861344
TI  - Acute psychiatric disorders in foreign domestic workers in Hong Kong: a pilot
      study.
AB  - AIM: To explore the psychopathology of foreign domestic workers (FDWs) who had an
      acute psychiatric disorder in Hong Kong. METHOD: This was a retrospective chart
      review. Demographic and clinical data were extracted from case records of FDWs
      who were admitted for the first time as inpatients for psychiatric treatment to
      three regional hospitals of the same catchment area in Hong Kong between 2000 and
      2004. Relevant socio-demographic data on local FDWs and the general population of
      Hong Kong were obtained from local government departments. RESULTS: Twenty-seven
      Filipino and 14 Indonesian FDWs presenting with their first and so far only
      psychiatric admission were identified. There were significantly more FDWs who
      were single or never married in the sample. Filipino FDWs tended to fall ill
      after 4 years of service in Hong Kong while the corresponding figure for
      Indonesian FDWs was 2 years. Indonesian FDWs were older and had less access to
      social and medical services than their Filipino counterparts. Home sickness and
      marital problems were more commonly identified as stressors rather than work
      related difficulties. Acute and Transient Psychotic Disorder (ICD-10) was
      diagnosed in over 60% of the subjects, making FDWs two times more vulnerable than
      local women of similar age for this illness. CONCLUSIONS: FDWs constitute a
      vulnerable group in terms of psychiatric morbidity. Concerted political, social
      and psychological efforts would be require to alleviate the distress faced by
      this particularly disadvantaged subset of female expatriates.

PMID- 19861345
TI  - The angiotensin II type 2 receptor in renal disease.
AB  - Suppression of angiotensin II formation by angiotensin-converting enzyme
      inhibitors or blockade of the angiotensin II receptor by angiotensin receptor
      blockers is a powerful therapeutic strategy to slow the progression of renal
      disease. However, angiotensin-converting enzyme inhibitors and angiotensin
      receptor blockers provide only imperfect protection against the progression of
      chronic kidney disease to end-stage renal failure. Hence, innovative approaches
      are needed to keep patients with chronic kidney disease off dialysis. Angiotensin
      II activates at least two receptors, namely the angiotensin II type 1 (AT( 1))
      and angiotensin II type 2 (AT(2)) receptors. The majority of the effects of
      angiotensin II, such as vasoconstriction, inflammation, and matrix deposition,
      are mediated via the AT(1) receptor. It is thought that the AT(2) receptor
      counteracts these effects and plays a role in nephroprotection. However, recent
      data support the notion that the AT(2) receptor transduces pro-inflammatory
      effects and promotes fibrosis and hypertrophy. Therefore, the question of whether
      stimulation of the AT(2) receptor could represent a silver bullet for the
      treatment of chronic kidney disease or may, on the contrary, exert detrimental
      effects on renal physiology remains unresolved. Recent data from AT(2) receptor
      knockout mice demonstrate that the loss of AT(2) receptor signalling is
      associated with increased renal injury and mortality in chronic kidney disease.
      This raises the expectation that pharmacological stimulation of the AT(2)
      receptor may positively influence renal pathologies. However, further research is
      needed to explore the question whether AT(2) receptor stimulation may represent a
      new therapeutic strategy for the treatment of chronic kidney disease.

PMID- 19861346
TI  - The role of the central renin-angiotensin system in Parkinson's disease.
AB  - Since the discovery of a renin-angiotensin system (RAS) in the brain, several
      studies have linked this central RAS to neurological disorders such as ischaemia,
      Alzheimer's disease and depression. In the last decade, evidence has accumulated
      that the central RAS might also play a role in Parkinson's disease. Although the
      exact cause of this progressive neurodegenerative disorder of the basal ganglia
      remains unidentified, inflammation and oxidative stress have been suggested to be
      key factors in the pathogenesis and the progression of the disease. Since
      angiotensin II is a pro-inflammatory compound that can induce the production of
      reactive oxygen species due to activation of the NADPH-dependent oxidase complex,
      this peptide might contribute to dopaminergic cell death. In this review, three
      different strategies to interfere with the pathogenesis or the progression of
      Parkinson's disease are discussed. They include inhibition of the angiotensin
      converting enzyme, blockade of the angiotensin II type 1 receptor and stimulation
      of the angiotensin II type 2 receptor.

PMID- 19861347
TI  - The angiotensin II type 2 receptor and the kidney.
AB  - Recent knowledge demonstrated that the renin-angiotensin system (RAS) functions
      as a local renal paracrine system. All components of the RAS are present within
      the kidney and include angiotensinogen, renin, angiotensin I, angiotensin
      converting enzymes, angiotensin II, the angiotensin II type 1 (AT(1)) receptor
      and the angiotensin II type 2 (AT(2)) receptor. Angiotensin II is the major
      effector hormone of the RAS and contributes to a variety of renal and
      cardiovascular physiologic and pathologic mechanisms through stimulation of AT(1)
      and AT(2) receptors. Angiotensin receptor blockers were developed based on the
      advanced knowledge of the AT(1) receptor contribution to development of a variety
      of kidney, vascular and cardiac diseases including but not limited to
      hypertension, diabetic nephropathy, heart failure, myocardial infarction and
      atherosclerosis. In contrast, knowledge concerning the role of the AT(2) receptor
      in health and disease is still emerging. The AT(2) receptor is believed to
      counterbalance the effects of the AT(1) receptor through influencing cellular
      differentiation, vasodilation, inhibition of cellular proliferation and
      hypertrophy, nitric oxide production and natriuresis. Thus, the pursuit of a
      specific AT(2) receptor agonist is a potentially fruitful area for combating
      renal and cardiovascular diseases. This review focuses on the role of the AT(2)
      receptor in the kidney.

PMID- 19861348
TI  - The past, present and future of angiotensin II type 2 receptor stimulation.
AB  - Studying the angiotensin type 2 receptor (AT(2)) has been problematic in the past
      because a pharmacological tool for direct, specific in vitro and in vivo
      stimulation of the receptor has been lacking. Consequently, current knowledge
      about AT(2) receptor signalling and function had to be obtained by indirect
      approaches, like studying animals or cells with genetically altered AT(2)
      receptor expression levels, inhibitory experiments using specific AT(2) receptor
      antagonists, stimulation with angiotensin II under concomitant angiotensin II
      type 1 receptor blockade or stimulation with the peptide agonist CGP42112A, which
      has additional AT(2) receptor antagonistic properties. The recently developed non
      peptide AT(2) receptor agonist Compound 21 now, for the first time, allows
      direct, selective and specific AT(2) receptor stimulation in vitro and in vivo.
      This new tool will certainly revolutionize AT(2) receptor research, enable many
      new insights into AT(2) receptor function and may also have the potential to
      become a future medical drug. This article reviews milestone findings about AT(2)
      receptor functional properties obtained by 'conventional' experimental approaches
      within the last 20 years. Moreover, it provides an overview of the first results
      obtained by direct AT(2) receptor stimulation with Compound 21, comprising
      effects on alkaline secretion, neurite outgrowth, blood pressure and post-infarct
      cardiac function.

PMID- 19861349
TI  - The angiotensin II type 2 receptor in cardiovascular disease.
AB  - Angiotensin II (Ang II) is considered the major final mediator of the renin
      angiotensin system. The actions of Ang II have been implicated in many
      cardiovascular conditions, such as hypertension, atherosclerosis, coronary heart
      disease, restenosis, and heart failure. Ang II can act through two different
      receptors: Ang II type 1 (AT(1)) receptor and Ang II type 2 (AT(2)) receptor. The
      AT(1) receptor is ubiquitously expressed in the cardiovascular system and
      mediates most of the physiological and pathophysiological actions of Ang II. The
      AT(2) receptor is highly expressed in the developing foetus, but its expression
      is very low in the cardiovascular system of the normal adult. Expression of the
      AT(2) receptor can be modulated by pathological states associated with tissue
      remodelling or inflammation such as hypertension, atherosclerosis, and myocardial
      infarction. The precise role of the AT(2) receptor remains under debate. However,
      it appears that the AT(2) receptor plays a vasodilatory role, and may be enhanced
      as a countervailing mechanism in cardiac hypertrophy, and in presence of vascular
      injury in hypertension and atherosclerosis. Signalling pathways induced by the
      stimulation of the AT(2) receptor are poorly understood, but three main
      mechanisms have been described: (a) activation of protein phosphatases causing
      protein dephosphorylation; (b) activation of bradykinin/nitric oxide/cyclic
      guanosine 3',5'-monophosphate pathway; and (c) stimulation of phospholipase A(2)
      and release of arachidonic acid. Vasodilatory effects of the AT(2) receptor,
      probably the only well-established role of the AT(2) receptor, have been
      attributed to the second of these mechanisms. The participation of the AT(2)
      receptor in cardiovascular remodelling and inflammation is more controversial. In
      vitro, AT(2) receptor stimulation clearly inhibits cardiac and vascular smooth
      muscle growth and proliferation, and stimulates apoptosis. In vivo, the situation
      is less clear, and depending on the studies, the AT(2) receptor appears to be
      required for cardiac hypertrophic growth or contrariwise, the AT(2) receptor has
      demonstrated no effects on cardiac hypertrophy. Similar controversial findings
      have been reported in atherosclerosis. Here we discuss the role of the AT(2)
      receptor on cardiovascular structure and disease, and the signalling pathways
      induced by its activation.

PMID- 19861350
TI  - Compound 21, the first orally active, selective agonist of the angiotensin type 2
      receptor (AT2): implications for AT2 receptor research and therapeutic potential.

PMID- 19861351
TI  - Angiotensin II type 2 receptor gene polymorphisms in cardiovascular disease.
AB  - Considerable progress in our understanding of the role of the angiotensin II type
      2 (AT(2)) receptor in the development of cardiac hypertrophy and coronary artery
      disease has been achieved using in vitro and in vivo animal models. Our
      understanding in humans, however, has been hindered by the lack of availability
      of specific AT(2) receptor agonists and antagonists suitable for human study.
      Nevertheless, an alternative approach involving genotyping humans for a
      functional polymorphism within the AT(2) receptor gene (-1332G/A) has been used
      in several association studies to elucidate the pathogenic role of the AT(2)
      receptor in cardiovascular disease. Both the A allele and the G allele have
      independently been associated with left ventricular remodelling. However, the
      methods of measuring left ventricular mass, sodium balance, age and degree of
      remodelling appear to influence the outcome. An association of carriers of the G
      allele and premature coronary artery disease has also been established,
      particularly in males presenting with stenotic atherosclerosis requiring
      revascularisation. At the molecular level, it remains unclear as to whether
      carriers of the G allele express more or fewer AT(2) receptors when compared to
      carriers of the A allele. Consequently, it is presently not possible to
      definitively interpret the role of the AT(2) receptor in human cardiovascular
      disease from these association studies.

PMID- 19861352
TI  - The angiotensin II type 2 receptor and the gastrointestinal tract.
AB  - The renin-angiotensin system (RAS) is well known for its vital involvement in
      body fluid homeostasis and circulation. However, very little research has been
      devoted to the impact of this regulatory system on the gastrointestinal (GI)
      system. This is surprising because the GI tract is fundamental for the intake and
      excretion of fluid and electrolytes (and nutrients), and it accommodates a large
      proportion of bodily haemodynamics and host defence systems. The RAS is well
      expressed and active in the GI tract, although the exact roles for the key
      mediator angiotensin II (Ang II) and its receptors in general, and the type 2
      (AT( 2)) receptor in particular, are not completely settled. There are several
      reports showing Ang II regulation of intestinal fluid and electrolyte transport.
      For example, mucosaprotective duodenal bicarbonate-rich secretion is inhibited by
      Ang II via type 1 (AT(1)) receptor-mediated facilitation of sympathoadrenergic
      activity, but this secretory process can also be stimulated by Ang II via AT(2)
      receptors. Novel data from human oesophagus and jejunum suggest that the AT(1)
      receptor mediates muscular contractions and that the AT(2) receptor regulates
      epithelial functions. Data are accumulating suggesting involvement of AT(1) and
      AT(2) receptors in GI inflammation and carcinogenesis. The picture of the RAS and
      AT( 2) receptor in the GI tract is, however, far from complete. Much more basic
      research is needed with regard to GI pathophysiology before concluding clinical
      significance and potential applicability of pharmacological interferences with
      the RAS.

PMID- 19861353
TI  - The angiotensin II type 2 receptor in the brain.
AB  - Recent clinical studies indicate that blockade of the renin-angiotensin system is
      important to prevent stroke, and accumulating results of basic research also
      indicate the possible involvement of the central renin-angiotensin system in
      ischaemic brain damage and cognition. When the angiotensin II type 1 receptor is
      blocked by an angiotensin type 1 receptor blocker, unbound angiotensin II acts
      preferentially on the angiotensin II type 2 (AT(2)) receptor. These results
      suggest the pathophysiological importance of the AT(2) receptor in the clinical
      use of angiotensin type 1 receptor blockers, which are widely used in patients
      with hypertension with the expectation of a decrease in the onset of
      cardiovascular and cerebrovascular disease. We review here the possible roles of
      AT(2) receptor activation in the brain, focusing on ischaemic stroke, cognitive
      function and neurogenesis, and potential effects of specific AT(2) receptor
      agonists.

PMID- 19861354
TI  - Computational protein profile similarity screening for quantitative mass
      spectrometry experiments.
AB  - MOTIVATION: The qualitative and quantitative characterization of protein
      abundance profiles over a series of time points or a set of environmental
      conditions is becoming increasingly important. Using isobaric mass tagging
      experiments, mass spectrometry-based quantitative proteomics deliver accurate
      peptide abundance profiles for relative quantitation. Associated data analysis
      workflows need to provide tailored statistical treatment that (i) takes the
      correlation structure of the normalized peptide abundance profiles into account
      and (ii) allows inference of protein-level similarity. We introduce a suitable
      distance measure for relative abundance profiles, derive a statistical test for
      equality and propose a protein-level representation of peptide-level
      measurements. This yields a workflow that delivers a similarity ranking of
      protein abundance profiles with respect to a defined reference. All procedures
      have in common that they operate based on the true correlation structure that
      underlies the measurements. This optimizes power and delivers more intuitive and
      efficient results than existing methods that do not take these circumstances into
      account. RESULTS: We use protein profile similarity screening to identify
      candidate proteins whose abundances are post-transcriptionally controlled by the
      Anaphase Promoting Complex/Cyclosome (APC/C), a specific E3 ubiquitin ligase that
      is a master regulator of the cell cycle. Results are compared with an established
      protein correlation profiling method. The proposed procedure yields a 50.9-fold
      enrichment of co-regulated protein candidates and a 2.5-fold improvement over the
      previous method. AVAILABILITY: A MATLAB toolbox is available from
      http://hci.iwr.uni-heidelberg.de/mip/proteomics.

PMID- 19861355
TI  - The GNUMAP algorithm: unbiased probabilistic mapping of oligonucleotides from
      next-generation sequencing.
AB  - MOTIVATION: The advent of next-generation sequencing technologies has increased
      the accuracy and quantity of sequence data, opening the door to greater
      opportunities in genomic research. RESULTS: In this article, we present GNUMAP
      (Genomic Next-generation Universal MAPper), a program capable of overcoming two
      major obstacles in the mapping of reads from next-generation sequencing runs.
      First, we have created an algorithm that probabilistically maps reads to repeat
      regions in the genome on a quantitative basis. Second, we have developed a
      probabilistic Needleman-Wunsch algorithm which utilizes _prb.txt and _int.txt
      files produced in the Solexa/Illumina pipeline to improve the mapping accuracy
      for lower quality reads and increase the amount of usable data produced in a
      given experiment. AVAILABILITY: The source code for the software can be
      downloaded from http://dna.cs.byu.edu/gnumap.

PMID- 19861356
TI  - Estimating population haplotype frequencies from pooled SNP data using incomplete
      database information.
AB  - MOTIVATION: Information about haplotype structures gives a more detailed picture
      of genetic variation between individuals than single-locus analyses. Databases
      that contain the most frequent haplotypes of certain populations are developing
      rapidly (e.g. the HapMap database for single-nucleotide polymorphisms in humans).
      Utilization of such prior information about the prevailing haplotype structures
      makes it possible to estimate the haplotype frequencies also from large DNA
      pools. When genetic material from dozens of individuals is pooled together and
      analysed in a single genotyping, the overall number of genotypings and the costs
      of the genetic studies are reduced. RESULTS: A Bayesian model for estimating the
      haplotypes and their frequencies from pooled allelic observations is introduced.
      The model combines an idea of using database information for haplotype estimation
      with a computationally efficient multinormal approximation. In addition, the
      model treats the number and structures of the unknown haplotypes as random
      variables whose joint posterior distribution is estimated. The results on real
      human data from the HapMap database show that the proposed method provides
      significant improvements over the existing methods. AVAILABILITY: A reversible
      jump Markov chain Monte Carlo algorithm for analysing the model is implemented in
      a program called Hippo (Haplotype estimation under incomplete prior information
      using pooled observations). For comparisons, an approximate expectation
      maximization algorithm (EM-algorithm) that utilizes database information about
      the existing haplotypes is implemented in a program called AEML. The source codes
      written in C (using GNU Scientific Library) are available at www.iki.fi/
      approximately mpirinen. CONTACT: matti.pirinen@iki.fi

PMID- 19861357
TI  - The performance of compartmental and physiologically based recirculatory
      pharmacokinetic models for propofol: a comparison using bolus, continuous, and
      target-controlled infusion data.
AB  - BACKGROUND: With the growing use of pharmacokinetic (PK)-driven drug delivery
      and/or drug advisory displays, identifying the PK model that best characterizes
      propofol plasma concentration (Cp) across a variety of dosing conditions would be
      useful. We tested the accuracy of 3 compartmental models and 1 physiologically
      based recirculatory PK model for propofol to predict the time course of propofol
      Cp using concentration-time data originated from studies that used different
      infusion schemes. METHODS: Three compartmental PK models for propofol, called the
      "Marsh," the "Schnider," and the "Schuttler" models, and 1 physiologically based
      recirculatory model called the "Upton" model, were used to simulate the time
      course of propofol Cp. To test the accuracy of the models, we used published
      measured plasma concentration data that originated from studies of manual (bolus
      and short infusion) and computer-controlled (target-controlled infusion [TCI] and
      long infusion) propofol dosing schemes. Measured/predicted (M/P) propofol Cp
      plots were constructed for each dataset. Bias and inaccuracy of each model were
      assessed by median prediction error (MDPE) and median absolute prediction error
      (MDAPE), respectively. RESULTS: The M/P propofol Cp in the 4 PK models revealed
      bias in all 3 compartmental models during the bolus and short infusion regimens.
      In the long infusion, a worse M/P propofol Cp at higher concentration was seen
      for the Marsh and the Schuttler models than for the 2 other models. Less biased
      M/P propofol Cp was found for all models during TCI. In the bolus group, after 1
      min, a clear overprediction was seen for all 3 compartmental models for the
      entire 5 min; however, this initial error resolved after 4 min in the Schnider
      model. The Upton model did not predict propofol Cp accurately (major
      overprediction) during the first minute. During the bolus and short infusion, the
      Marsh model demonstrated worse MDPE and MDAPE compared with the 3 other models.
      During short infusion, MDAPE for the Schnider and Schuttler models was better
      than the Upton and the Marsh models. All models showed similar MDPE and MDAPE
      during TCI simulations. During long infusion, the Marsh and the Schuttler models
      underestimated the higher plasma concentrations. CONCLUSION: When combining the
      performance during various infusion regimens, it seems that the Schnider model,
      although still not perfect, is the recommended model to be used for TCI and
      advisory displays.

PMID- 19861358
TI  - Hemispheric synchronized sounds and perioperative analgesic requirements.
AB  - BACKGROUND: Data on the effect of Hemisync sounds on perioperative analgesic
      requirements are scant. METHODS: We randomized surgical outpatients into a
      treatment group that received Hemisync sounds (n = 20), a music group that
      received music (n = 20), and a control group that had a blank cassette tape (n =
      20). All subjects underwent a controlled standardized propofol-nitrous-vecuronium
      and fentanyl general anesthesia. RESULTS: The treatment group had significantly
      reduced intraoperative fentanyl consumption (P < 0.05). Postoperatively, pain
      visual analog scale scores were significantly lower in the Hemisync group at 1 h
      (P = 0.02) and 24 h (P = 0.005). Subjects in the Hemisync group were also
      discharged earlier (P = 0.048). CONCLUSION: The use of Hemisync sounds before and
      during general anesthesia reduces intraoperative analgesic requirements,
      postoperative pain scores, and discharge time.

PMID- 19861359
TI  - References to anesthesia, pain, and analgesia in the Hippocratic Collection.
AB  - The Hippocratic Collection, containing 60 medical texts by Hippocrates and his
      pupils, was searched using the electronic database Thesaurus Lingua Graeca to
      identify the words "anaesthesia" and "analgesia," their derivatives and also
      words related to pain. Our purpose was to investigate the special use and meaning
      of these words and their significance in medical terms. The word "anaesthesia"
      appears 12 times in five Hippocratic texts to describe loss of sensation by a
      disease process. This observation reveals Hippocrates as the first Greek writer
      to use the word in a medical rather than a philosophical context. Hippocrates was
      also the first Greek physician to keep an airway open by bypassing a pharyngeal
      obstruction with the insertion of narrow tubes into the swollen throat of a
      patient with quinsy, thus facilitating the airflow into the lungs. In the
      Hippocratic texts, "analgesia" is related to "anaesthesia" for the first time,
      when it is pointed out that an unconscious patient is insensitive to pain.
      Hippocrates and his followers rationalized pain as a clinical variable and as a
      valuable diagnostic and prognostic tool. They used expressive and precise
      adjectives and well-defined characteristics of pain, such as location, duration,
      or relation to other symptoms, to elucidate a disease process. They also had a
      wide terminology for the various types of pain, still in use today. Many cures
      were described for the treatment of pain, including incisions, effusions,
      venesection, purges, cauterization and, most interestingly, the use of many
      plants, such as opium or the application of soporific substances. In particular,
      Hippocrates refers to opium poppy as "sleep inducing."

PMID- 19861360
TI  - Dental sedation by dentists: a view from anesthesiologists working in central
      Western Brazil.
AB  - BACKGROUND: Anesthesia care has been provided by diverse health professionals
      worldwide, but little is known about anesthesiologists' views about this. Using a
      survey, we sought the opinions of a group of Brazilian anesthesiologists
      regarding nitrous oxide/oxygen and oral minimal/moderate sedation performed by
      dentists. METHODS: A 3-part postal questionnaire was sent to 206 physician
      anesthesiologists working in the state of Goias, in Central Western Brazil. Part
      1 consisted of 4 questions describing respondents' characteristics: gender, time
      elapsed since completion of the residency program, and experience in providing
      sedation and general anesthesia for dental treatment. In Part 2, respondents were
      asked to give their opinions on 11 statements about sedation performed by
      dentists. Possible responses ranged from total disagreement to total agreement
      (minimum score = 11 and maximum score = 55). Part 3 was a section for general
      comments. Data were analyzed by k-means clusters, chi(2), and Student's t-test.
      RESULTS: The response rate was 53.8% (111 questionnaires). Most anesthesiologists
      (85.6%) had rarely or never provided sedation or general anesthesia for dental
      treatment, and 92.8% disagreed with the statement that dentists can administer
      moderate sedation in the dental office. Two clusters representing more favorable
      (n = 21) or less favorable (n = 90) opinions were established. Anesthesiologists
      in the "less favorable" group had more experience with dental sedation (P =
      0.006) and dental general anesthesia (P = 0.008) than those in the "more
      favorable" group. Gender and time elapsed since residency completion did not
      significantly affect anesthesiologists' opinions. CONCLUSIONS: Many
      anesthesiologists in Central Western Brazil do not sedate dental patients and are
      not confident that dentists are able to do it. Dental sedation is an issue that
      still needs to be clarified in this region; the respective roles of physicians
      and dentists need to be determined to benefit the population.

PMID- 19861361
TI  - The impact of cardiopulmonary bypass on systemic interleukin-6 release, cerebral
      nuclear factor-kappa B expression, and neurocognitive outcome in rats.
AB  - BACKGROUND: Neurocognitive deficits after cardiac surgery with cardiopulmonary
      bypass (CPB) continue to affect patients' quality of life, and an inflammatory
      reaction may be one of the contributors. We designed this experiment to study
      perioperative systemic interleukin-6 (IL-6) concentrations, cerebral expression
      of nuclear factor-kappa B (NF-kappaB), and neurocognitive outcome after CPB in
      young rats. The impact of oxygenator size on these outcomes was also assessed.
      METHODS: Rats were randomly assigned to 1 of 4 groups: control (n = 7,
      nonanesthetized), sham-operated rats (n = 10, anesthetized, cannulated, and not
      connected to CPB), and 2 CPB groups, anesthetized, cannulated, and subjected to
      90 min of CPB, using either a small-volume rat oxygenator (CPB/rat oxygenator, n
      = 10) or a neonate oxygenator (CPB/neonate oxygenator, n = 10). Systemic IL-6 was
      determined before, at the end of, and 2 h after CPB or at equivalent times.
      Hippocampal NF-kappaB expression was assessed on postoperative day 21 using
      immunohistochemistry. Neurocognitive performance was assessed with the modified
      hole-board test at baseline and for 21 postoperative days. RESULTS: Both CPB
      groups had increased systemic IL-6 levels compared with sham, with the neonate
      oxygenator causing a substantially larger increase at 2 h after CPB compared with
      the rat oxygenator group (CPB/rat oxygenator: 220 pg/mL [16-415]; CPB/neonate
      oxygenator: 1400 pg/mL [592-5812]) (P < 0.05). Hippocampal NF-kappaB was
      increased in experimental groups compared with controls (10 +/- 4). CPB resulted
      in more NF-kappaB-positive neurons (271 +/- 57 CPB/neonate oxygenator and 269 +/-
      72 CPB/rat oxygenator) compared with sham operation (173 +/- 24). Neurocognitive
      and behavioral performances were unaltered and comparable among all groups.
      CONCLUSIONS: Pronounced systemic inflammatory responses to experimental CPB
      associated with increased hippocampal expression of NF-kappaB were not
      accompanied by neurocognitive impairment. This suggests that other factors beyond
      CPB and inflammatory responses might contribute to adverse neurocognitive
      outcomes after cardiac surgery.

PMID- 19861362
TI  - The GlideScope facilitates nasogastric tube insertion: a randomized clinical
      trial.
AB  - BACKGROUND: The GlideScope (Saturn Biomedical Systems, B.C., Canada) is a
      reusable videolaryngoscope and is considered an effective device for tracheal
      intubation. We designed this study to evaluate the application of this device in
      nasogastric tube (NGT) insertion. METHODS: This randomized clinical trial was
      performed at a teaching hospital on 80 adult patients who required intraoperative
      placement of an NGT. The patients were divided into 2 groups (the control and the
      GlideScope group) using computerized, random allocation software. In the control
      group, the NGT was inserted blindly as commonly performed in operating rooms;
      however, in the GlideScope group, the tube was inserted with the assistance of a
      GlideScope. The number of attempts for NGT insertion and the time required for
      inserting the NGT properly along with the occurrence of possible complications
      were recorded. RESULTS: The mean intubation time in the GlideScope group was 27.7
      +/- 20.7 s shorter than that in the control group. NGT insertion in the first
      attempt was successful in approximately 85% of the patients in the GlideScope
      group; in the control group, however, the tubes were inserted successfully after
      the first attempt in 57.5% of the patients. Complications were reported in 14
      patients (35%) of the control group and 8 patients (20%) of the GlideScope group.
      CONCLUSION: GlideScope facilitates NGT insertion and reduces the duration of the
      procedure.

PMID- 19861363
TI  - Activation of central opioid receptors induces cardioprotection against ischemia
      reperfusion injury.
AB  - BACKGROUND: Small doses of intrathecal morphine provide cardioprotection similar
      to that conferred by IV morphine and ischemic preconditioning (IPC). We
      investigated the relative role of central versus peripheral opioid receptors in
      intrathecal morphine preconditioning (ITMPC). METHODS: Forty-eight anesthetized,
      open-chest, male Sprague-Dawley rats were assigned to 1 of 7 treatment groups (n
      = 6-7) after successful intrathecal catheter placement. ITMPC was achieved by 3
      consecutive 5-min intrathecal infusions of morphine (1.0 microg/kg each). This
      was repeated in the presence of either IV (IV naloxone methiodide + ITMPC) or
      intrathecally (intrathecal naloxone methiodide [ITNM] + ITMPC) administered
      naloxone methiodide. This compound was also given via these same routes in the
      absence of ITMPC (IV naloxone methiodide + ITNM). Intrathecal normal saline and
      IPC were used as negative and positive controls, respectively. Myocardial
      ischemia and reperfusion injury were induced by 30 min of left main coronary
      artery occlusion followed by 2 h of reperfusion. Myocardial infarct size, as a
      percentage of the area-at-risk, was determined by 2,3,5-triphenyltetrazolium
      staining. RESULTS: The infarct size/area-at-risk were significantly reduced in
      the IPC (22% +/- 3%) and ITMPC (26% +/- 5%) groups compared with the control
      group (48% +/- 9%) (P < 0.01). The addition of ITNM reversed the cardioprotective
      effects of ITMPC (45% +/- 4%), whereas IV administration of the drug did not have
      any effect on ITMPC (28% +/- 9%, P < 0.01). CONCLUSIONS: Intrathecally
      administered morphine can produce cardioprotective effects via the activation of
      central opioid receptors, without the apparent involvement of peripheral opioid
      receptors.

PMID- 19861365
TI  - Closed-circuit xenon delivery using a standard anesthesia workstation.
AB  - BACKGROUND: Xenon (Xe) is an anesthetic with minimal side effects, now also
      showing promise as a neuroprotectant both in vitro and in vivo. Although scarce
      and expensive, Xe is insoluble and patient uptake is low, making closed circuits
      the optimum delivery method. Although the future of Xe anesthesia is uncertain,
      effective neuroprotection is highly desirable even if moderately expensive. A
      factor limiting Xe research in all these fields may be the perceived need to
      purchase special Xe anesthesia workstations that are expensive and difficult to
      service. We investigated the practicality of 1) true closed-circuit Xe delivery
      using an unmodified anesthesia workstation with gas monitoring/delivery
      attachments restricted to breathing hoses only, 2) a Xe delivery protocol
      designed to eliminate wastage, and 3) recovering Xe from exhaled gas. METHODS:
      Sixteen ASA physical status I/II patients were recruited for surgery of > 2 h.
      Denitrogenation with 100% oxygen was started during induction and tracheal
      intubation under propofol/remifentanil anesthesia. This continued after operating
      room transfer for 30 min. All fresh gases were then temporarily stopped,
      metabolic oxygen consumption then being replaced with 250-mL Xe boluses until
      F(I)Xe = 50%. A basal oxygen fresh gas flow was thereafter restored with
      additional Xe given as required via the expiratory hose to maintain a F(I)Xe > or
      = 50%. At no time, apart from during circle flushes every 90 min, were the
      bellows allowed to completely fill and spill gas, ensuring the circle remained
      closed. On termination of anesthesia, the first 10 exhaled breaths were collected
      as was residual gas from the circle, allowing measurement of the Xe content of
      each. RESULTS: Total Xe consumption, including initial wash-in and circle
      flushes, was 12.62 (5.31) L or 4.95 (0.82) L/h, mean (sd). However, consumption
      during maintenance periods was lower: 3 L/h at 1 h and 2 L/h thereafter. Of the
      total Xe used, 8.98% (5.94%) could be recovered at the end of the procedure.
      CONCLUSIONS: We report that closed-circuit Xe delivery can be achieved with a
      modified standard anesthesia workstation with breathing hose alterations only and
      that the protocol was very gas efficient, especially during the normally wasteful
      Xe wash-in. A Xe mixture of > or = 50% was delivered for up to 341 min (5 h 41
      min) and Xe consumption was 4.95 (0.82) L/h, maintenance being achieved with 2-3
      L/h. With this degree of efficiency, Xe recovery/recycling at the end of
      anesthesia may be of little additional benefit.

PMID- 19861364
TI  - Posttraumatic stress disorder in aware patients from the B-aware trial.
AB  - BACKGROUND: The long-term consequences of an awareness episode vary. Some
      patients do not have any long-term disability, whereas others develop
      psychological problems that may be severe and persistent. In this study, we
      compared the incidence of posttraumatic stress disorder (PTSD) in patients with
      and without confirmed awareness who were randomized in the B-Aware Trial.
      METHODS: We used a matched cohort design, aiming to follow up the 13 patients
      with confirmed awareness. Each surviving awareness patient was matched with 4
      controls for age, sex, surgery type, date of surgery, and hospital. A face-to
      face interview was conducted with each awareness patient and matched controls
      using the Clinician Administered Posttraumatic Stress Disorder Scale. RESULTS:
      Data collection for this study occurred between June 2006 and March 2007, with a
      median follow-up time of 5.3 yr (range, 4.3-5.7 yr). Six of the 13 confirmed
      awareness patients had died. Five of the 7 confirmed awareness patients (71%) and
      3 of the 25 controls (12%) fulfilled the criteria for PTSD at the time of the
      interview (adjusted odds ratio = 13.3 [95% confidence interval: 1.4-650]; P =
      0.02). The median onset time of symptoms was 14 days (range, 7-243 days) after
      surgery, and the median duration of symptoms was 4.7 yr (range, 4.4-5.6 yr).
      CONCLUSIONS: PTSD was common and persistent in the confirmed awareness patients
      of the B-Aware Trial. Strategies to prevent awareness in patients under general
      anesthesia are justified.

PMID- 19861366
TI  - A clinical prediction rule for pulmonary complications after thoracic surgery for
      primary lung cancer.
AB  - BACKGROUND: There is controversy surrounding the value of the predicted
      postoperative diffusing capacity of lung for carbon monoxide (DLCOppo) in
      comparison to the forced expired volume in 1 s for prediction of pulmonary
      complications (PCs) after thoracic surgery. METHODS: Using a prospective
      database, we performed an analysis of 956 patients who had resection for lung
      cancer at a single institution. PC was defined as the occurrence of any of the
      following: atelectasis, pneumonia, pulmonary embolism, respiratory failure, and
      need for supplemental oxygen at hospital discharge. RESULTS: PCs occurred in 121
      of 956 patients (12.7%). Preoperative chemotherapy (odds ratio 1.64, 95%
      confidence interval 1.06-2.55, P = 0.02, point score 2) and a lower DLCOppo (odds
      ratio per each 5% decrement 1.13, 95% confidence interval 1.06-1.19, P < 0.0001,
      point score 1 per each 5% decrement of DLCOppo less than 100%) were independent
      risk factors for PCs. We defined 3 overall risk categories for PCs: low < or =10
      points, 39 of 448 patients (9%); intermediate 11-13 points, 37 of 256 patients
      (14%); and high > or =14 points, 42 of 159 patients (26%). The median (range)
      length of hospital stay was significantly greater for patients who developed PCs
      than for those who did not: 12 (3-113) days vs 6 (2-39) days, P < 0.0001,
      respectively. Similarly, 30-day mortality was significantly more frequent for
      patients who developed PCs than for those who did not: 16 of 121 (13.2%) vs 6 of
      835 (0.7%), P < 0.0001. CONCLUSIONS: These data show that PCs after thoracic
      surgery for lung cancer can be predicted with moderate accuracy based on DLCOppo
      and whether patients had chemotherapy. Forced expired volume in 1 s was not a
      predictor of PCs.

PMID- 19861367
TI  - Heparin concentration-based anticoagulation for cardiac surgery fails to reliably
      predict heparin bolus dose requirements.
AB  - BACKGROUND: Hemostasis management has evolved to include sophisticated point-of
      care systems that provide individualized dosing through heparin concentration
      based anticoagulation. The Hepcon HMS Plus system (Medtronic, Minneapolis, MN)
      estimates heparin dose, activated clotting time (ACT), and heparin dose response
      (HDR). However, the accuracy of this test has not been systematically evaluated
      in large cohorts. METHODS: We examined institutional databases for all patients
      who underwent cardiac surgery with cardiopulmonary bypass (CPB) at our
      institution from February 2005 to July 2008. During this period, the Hepcon HMS
      Plus was used exclusively for assessment of heparin dosing and coagulation
      monitoring. Detailed demographic, surgical, laboratory, and heparin dosing data
      were recorded. ACT, calculated and measured HDR, and heparin concentrations were
      recorded. Performance of the Hepcon HMS Plus was assessed by comparison of actual
      and target ACT values and calculated and measured HDR. RESULTS: In 3880 patients
      undergoing cardiac surgery, heparin bolus dosing to a target ACT resulted in wide
      variation in the postheparin ACT (r(2) = 0.03). The postheparin ACT did not reach
      the target ACT threshold in 7.4%(i.e., when target ACT was 300 s) and 16.9%
      (i.e., when target ACT was 350 s) of patients. Similarly, the target heparin
      level calculated from the HDR did not correlate with the postbolus heparin level,
      with 18.5% of samples differing by more than 2 levels of the assay. Calculated
      and measured HDR were not linearly related at any heparin level. CONCLUSIONS: The
      Hepcon HMS Plus system poorly estimates heparin bolus requirements in the pre-CPB
      period. Further prospective studies are needed to elucidate what constitutes
      adequate anticoagulation for CPB and how clinicians can reliably and practically
      assess anticoagulation in the operating room.

PMID- 19861368
TI  - Ultrasonography as a preoperative assessment tool: predicting the feasibility of
      central neuraxial blockade.
AB  - A woman with severe ankylosing spondylitis presented to the preanesthetic clinic
      before total hip arthroplasty. She had required general anesthesia with
      fiberoptic intubation after failed attempts at spinal anesthesia for previous hip
      surgery. Using a portable ultrasound unit, we identified an open L4-5
      interlaminar space and offered the patient an ultrasound-guided spinal
      anesthetic. Dural puncture with a single needle pass was subsequently achieved
      with the aid of preprocedural ultrasound imaging. Ultrasound may be a useful
      preoperative assessment tool for assessing the feasibility of central neuraxial
      blockade when technical difficulty is anticipated.

PMID- 19861371
TI  - An eye on profit.

PMID- 19861369
TI  - Differences in atherosclerosis according to area level socioeconomic deprivation:
      cross sectional, population based study.
AB  - OBJECTIVES: To examine the relation between area level social deprivation and
      ultrasound markers of atherosclerosis (common carotid intima-media thickness and
      plaque score), and to determine whether any differences can be explained by
      "classic" (currently recognised) or "emerging" (novel) cardiovascular risk
      factors. DESIGN: Cross sectional, population based study. SETTING: NHS Greater
      Glasgow Health Board area. PARTICIPANTS: 666 participants were selected on the
      basis of how their area ranked in the Scottish Index of Multiple Deprivation
      2004. Approximately equal numbers of participants from the most deprived areas
      and the least deprived areas were included, as well as equal numbers of men and
      women and equal numbers of participants from each age group studied (35-44, 45
      54, and 55-64 years). MAIN OUTCOME MEASURES: Carotid intima-media thickness and
      plaque score, as detected by ultrasound. RESULTS: The mean age and sex adjusted
      intima-media thickness was significantly higher in participants from the most
      deprived areas than in those from the least deprived areas (0.70 mm (standard
      deviation (SD) 0.16 mm) v 0.68 mm (SD 0.12 mm); P=0.015). On subgroup analysis,
      however, this difference was only apparent in the highest age tertile in men
      (56.3-66.5 years). The difference in unadjusted mean plaque score between
      participants from the most deprived and those from the least deprived areas was
      more striking than the difference in intima-media thickness (least deprived 1.0
      (SD 1.5) v most deprived 1.7 (SD 2.0); P<0.0001). In addition, a significant
      difference in plaque score was apparent in the two highest age tertiles in men
      (46.8-56.2 years and 56.3-66.5 years; P=0.0073 and P<0.001) and the highest age
      tertile in women (56.3-66.5 years; P<0.001). The difference in intima-media
      thickness between most deprived and least deprived males remained significant
      after adjustment for classic risk factors, emerging risk factors, and individual
      level markers of socioeconomic status (P=0.010). Adjustment for classic risk
      factors and emerging cardiovascular risk factors, either alone or in combination,
      did not abolish the deprivation based difference in plaque presence (as a binary
      measure; adjusted odds ratio of 1.73, 95% confidence interval 1.07 to 2.82).
      However, adjustment for classic risk factors and individual level markers of
      early life socioeconomic status abolished the difference in plaque presence
      between the most deprived and the least deprived individuals (adjusted odds ratio
      0.94, 95% CI 0.54 to 1.65; P=0.84). CONCLUSIONS: Deprivation is associated with
      increased carotid plaque score and intima-media thickness. The association of
      deprivation with atherosclerosis is multifactorial and not adequately explained
      by classic or emerging risk factors.

PMID- 19861374
TI  - Red Cross calls for urgent medical help in face of growing civilian casualties
      from Pakistan conflict.

PMID- 19861376
TI  - Depression in adults, including those with a chronic physical health problem:
      summary of NICE guidance.

PMID- 19861375
TI  - Migraine and cardiovascular disease: systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the association between migraine and cardiovascular
      disease, including stroke, myocardial infarction, and death due to cardiovascular
      disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic
      databases (PubMed, Embase, Cochrane Library) and reference lists of included
      studies and reviews published until January 2009. Selection criteria Case-control
      and cohort studies investigating the association between any migraine or specific
      migraine subtypes and cardiovascular disease. Review methods Two investigators
      independently assessed eligibility of identified studies in a two step approach.
      Disagreements were resolved by consensus. Studies were grouped according to a
      priori categories on migraine and cardiovascular disease. DATA EXTRACTION: Two
      investigators extracted data. Pooled relative risks and 95% confidence intervals
      were calculated. RESULTS: Studies were heterogeneous for participant
      characteristics and definition of cardiovascular disease. Nine studies
      investigated the association between any migraine and ischaemic stroke (pooled
      relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses
      indicated a significantly higher risk among people who had migraine with aura
      (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23,
      0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results
      suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men
      (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use
      further increased the risk. Eight studies investigated the association between
      migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine
      and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study
      investigated the association between women who had migraine with aura and
      myocardial infarction and death due to cardiovascular disease, showing a twofold
      increased risk. CONCLUSION: Migraine is associated with a twofold increased risk
      of ischaemic stroke, which is only apparent among people who have migraine with
      aura. Our results also suggest a higher risk among women and risk was further
      magnified for people with migraine who were aged less than 45, smokers, and women
      who used oral contraceptives. We did not find an overall association between any
      migraine and myocardial infarction or death due to cardiovascular disease. Too
      few studies are available to reliably evaluate the impact of modifying factors,
      such as migraine aura, on these associations.

PMID- 19861377
TI  - Acceptability of A/H1N1 vaccination during pandemic phase of influenza A/H1N1 in
      Hong Kong: population based cross sectional survey.
AB  - OBJECTIVE: To investigate the intention of the Hong Kong general population to
      take up vaccination against influenza A/H1N1. Setting Cross sectional population
      based anonymous survey. Participants Random sample of 301 adults interviewed by
      telephone (response rate 80%). MAIN OUTCOME MEASURE: Intention to take up
      vaccination against influenza A/H1N1 under five hypothetical scenarios:
      vaccination is free; vaccination per dosage costs less than $HK100 ( pound8;
      euro9; $13), $HK101-200, or more than $HK200; and no data are available on the
      efficacy and safety of the vaccine. Results 45% (n=135) of the participants
      reported that they would be highly likely take up vaccination if it was free.
      When vaccination incurred a cost, however, the prevalence of uptake decreased:
      36% (n=108) would take up vaccination if it cost less than $HK100, 24% (n=72) if
      it cost $HK101-200, and 15% (n=45) if it cost more than $HK200; and in absence of
      proved efficacy and safety decreased to 5% (n=14). Moreover, 32% (n=95)
      considered universal A/H1N1 vaccination unnecessary. Overall, 39% (n=117) of
      participants believed that A/H1N1 vaccination would prevent the virus being
      contracted; 63% (n=189) erroneously believed that efficacy of the vaccine had
      been confirmed by clinical trials, and 16% (n=49) believed that it is necessary
      for everyone in Hong Kong to take up vaccination against influenza A/H1N1.
      Conclusions The uptake of vaccination against influenza A/H1N1 by the general
      population of Hong Kong is unlikely to be high and would be sensitive to personal
      cost. Evidence about safety and efficacy is critical in determining the
      prevalence of uptake of vaccination.

PMID- 19861379
TI  - Migraine with aura and increased risk of ischaemic stroke.

PMID- 19861380
TI  - BMA view on whistleblowing.

PMID- 19861382
TI  - Normal systolic blood pressure and risk of heart failure in US male physicians.
AB  - AIMS: Heart failure (HF) is a major public health issue and hypertension is a
      major predictor of HF. Observational studies have demonstrated a continuous and
      graded relationship between 'normal' systolic blood pressure (SBP) and
      cardiovascular disease. However, limited data are available on the relationship
      between normotensive SBP and the risk of HF. METHODS AND RESULTS: To test the
      hypothesis that there is a graded relation between SBP and HF risk among subjects
      with normal SBP, we used data on 18 876 participants who were healthy and were
      free of HF at baseline. Incident HF cases were ascertained by annual follow-up
      questionnaires and validated through a review of medical records. Cox
      proportional hazard model was used to compute multivariable-adjusted hazard
      ratios with corresponding 95% confidence intervals. Between 1982 and 2008, 1098
      cases of HF occurred. There was a 35% increased risk of HF among subjects with
      SBP 130-139 mmHg compared with people with optimal SBP (<120 mmHg). In addition,
      there was a linear trend in HF risk across the normal range of SBP. CONCLUSION:
      Our findings suggest a linear relationship between normotensive SBP and HF risk.
      Strategies to prevent HF, such as lifestyle modification, should be emphasized
      across all blood pressure ranges.

PMID- 19861381
TI  - A study in entire chromosomes of violations of the intra-strand parity of
      complementary nucleotides (Chargaff's second parity rule).
AB  - Chargaff's rule of intra-strand parity (ISP) between complementary
      mono/oligonucleotides in chromosomes is well established in the scientific
      literature. Although a large numbers of papers have been published citing works
      and discussions on ISP in the genomic era, scientists are yet to find all the
      factors responsible for such a universal phenomenon in the chromosomes. In the
      present work, we have tried to address the issue from a new perspective, which is
      a parallel feature to ISP. The compositional abundance values of
      mono/oligonucleotides were determined in all non-overlapping sub-chromosomal
      regions of specific size. Also the frequency distributions of the
      mono/oligonucleotides among the regions were compared using the Kolmogorov
      Smirnov test. Interestingly, the frequency distributions between the
      complementary mono/oligonucleotides revealed statistical similarity, which we
      named as intra-strand frequency distribution parity (ISFDP). ISFDP was observed
      as a general feature in chromosomes of bacteria, archaea and eukaryotes.
      Violation of ISFDP was also observed in several chromosomes. Chromosomes of
      different strains belonging a species in bacteria/archaea (Haemophilus influenza,
      Xylella fastidiosa etc.) and chromosomes of a eukaryote are found to be different
      among each other with respect to ISFDP violation. ISFDP correlates weakly with
      ISP in chromosomes suggesting that the latter one is not entirely responsible for
      the former. Asymmetry of replication topography and composition of forward
      encoded sequences between the strands in chromosomes are found to be insufficient
      to explain the ISFDP feature in all chromosomes. This suggests that multiple
      factors in chromosomes are responsible for establishing ISFDP.

PMID- 19861383
TI  - Prevalence of bacterial colonization of generator pockets in implantable
      cardioverter defibrillator patients without signs of infection undergoing
      generator replacement or lead revision.
AB  - AIMS: This study was designed to evaluate the prevalence of bacterial
      colonization of generator pockets in implantable cardioverter defibrillator (ICD)
      patients without signs of infection and to analyse the impact of bacterial
      colonization on the incidence of device infection during follow-up. METHODS AND
      RESULTS: In 122 ICD patients undergoing generator replacement or surgical lead
      revision between January 2006 and July 2008, microbiological cultures of
      generator pockets and extracted leads were consecutively obtained. Patients with
      clinical evidence of a device infection were excluded. Positive cultures from the
      generator pocket and leads were found in 40 (33%) patients. The most common
      bacteria isolated were coagulase negative staphylococci (68%). During a median
      follow-up time of 203 days after the revision device infection occurred in three
      [7.5%, confidence interval (CI) 1.6-20.4%] patients with a positive culture vs.
      two (2.4%, CI 0.3-8.5%) patients with a negative culture (P = 0.33). Time from
      revision to infection was 108 +/- 73 days in patients with positive culture vs.
      60 +/- 39 days in patients with negative culture (P = 0.50). CONCLUSION: A third
      of ICD patients undergoing generator replacement or lead revision have an
      asymptomatic bacterial colonization of generator pockets. After revision 7.5% of
      these patients develop a device infection with the same species of microorganism.

PMID- 19861384
TI  - Heart failure burden and therapy.
AB  - Heart failure (HF) is a syndrome with a broad spectrum of heterogeneous symptoms
      and signs resulting in a wide range of clinical expressions. The prevalence of HF
      is estimated to be 1-2% in developed countries, increasing with age. Heart
      failure is the leading cause of hospitalization for patients older than 65 years,
      raising concerns about the economic burden of this syndrome. This article
      provides a critical review of epidemiological and clinical aspects for HF;
      causes, comorbidities, and types of HF are also described. The systolic vs.
      diastolic, the acute vs. chronic approaches, and the connections between HF and
      left bundle branch block or atrial fibrillation are further detailed. In
      addition, a synthesis of the latest results and recommendations concerning the
      indication and the prescription of pharmacological (such as diuretics or rennin
      angiotensin-aldosterone system inhibitors) and non-pharmacological treatments
      (particularly device therapy) is proposed.

PMID- 19861385
TI  - Pathophysiological mechanisms underlying ventricular dyssynchrony.
AB  - Left ventricular dyssynchrony due to conduction system disease creates cardiac
      inefficiency even in normal hearts. Dyssynchrony in the failing heart results in
      the development of a discrete heart failure phenotype as it induces chamber
      heterogeneity at the cellular and molecular levels that leads to impaired
      excitation-contraction coupling, increased arrhythmia susceptibility, and
      decreased myocyte survival among other pathologic changes. Recent research has
      demonstrated that these biomolecular changes are amazingly reversed with cardiac
      resynchronization therapy, providing insight into how to target the therapy.

PMID- 19861386
TI  - The anatomy of the coronary sinus venous system for the cardiac
      electrophysiologist.
AB  - Cardiac electrophysiologists' use of the coronary sinus (CS) to map and ablate
      accessory pathways and implant left ventricular leads has emphasized the need for
      understanding CS anatomy. In this review, we briefly examine the developmental
      and radiological anatomy of the CS and discuss in detail the gross anatomy of
      this cardiac vein. We highlight the correlations of the acquired anatomical
      knowledge relevant to clinical electrophysiology practice.

PMID- 19861387
TI  - Lead positioning for cardiac resynchronization therapy: techniques and
      priorities.
AB  - Although cardiac resynchronization therapy (CRT) has demonstrated to be an
      effective treatment for heart failure patients, up to 30-40% of the patients do
      not show a favourable response. Implantation of the left ventricular (LV) pacing
      lead is one of the determinants of CRT response. This procedure includes several
      challenging technical issues and strongly depends on the highly variable anatomy
      of the coronary sinus and tributaries. In addition, the final position of the LV
      pacing lead may target the latest activated areas of the left ventricle in order
      to obtain effective resynchronization. Furthermore, the presence of transmural
      myocardial scar at the region targeted by the LV lead may also determine the
      response to CRT. This review discusses all the issues related to LV lead
      implantation and the role of multimodality imaging to anticipate the implantation
      strategy. Finally, alternative LV pacing sites and their effect on clinical
      outcome and LV performance will be discussed.

PMID- 19861388
TI  - Is there a need for more than one left ventricular lead in some patients?
AB  - Cardiac resynchronization therapy (CRT) is an effective treatment of heart
      failure in selected patients. However, with conventional CRT, notable left
      ventricular (LV) reverse remodelling is achieved in only 60-70% of patients. This
      lack of effect of CRT might be due to incomplete resynchronization. In some
      patients, the paced activation front arising from a single LV electrode is
      unfavourable, possibly resulting in suboptimal resynchronization. Dual-site LV
      CRT has theoretical advantages in faster and more physiological LV activation.
      Some clinical evidence supports dual LV pacing. Nevertheless, a clear benefit of
      this pacing modality in patients chronically implanted is still unproved. A
      randomized study comparing single- and dual-site LV pacing, the Triple-Site
      Cardiac Resynchronization study of Patients with Heart Failure (TRUST CRT) is
      still ongoing.

PMID- 19861389
TI  - The role of non-invasive imaging in patient selection.
AB  - Cardiac resynchronization therapy (CRT) is an established therapy for patients
      with advanced heart failure, depressed left ventricular (LV) function and wide
      QRS complex. A substantial amount of patients do not respond to CRT. Recent
      studies suggest that assessment of mechanical dyssynchrony may allow
      identification of potential CRT responders. In addition, presence of scar tissue
      and venous anatomy may play a role in the selection of candidates. This article
      summarizes the role of non-invasive cardiac imaging modalities addressing these
      issues in the selection of CRT candidates.

PMID- 19861390
TI  - The role of invasive mapping in the electrophysiology laboratory.
AB  - The role of invasive mapping in the context of cardiac resynchronization has been
      essentially confined to improving knowledge of the depolarization processes and
      spread of ventricular activation. Experimental and limited clinical data obtained
      from high resolution three-dimensional contact and non-contact mapping have
      consistently pointed to the heterogeneity and the complexity of ventricular
      sequential activation in heart failure with conduction disturbance. The present
      article reviews current knowledge about activation mapping in patients with
      different types of ventricular conduction disturbance (right and left bundle
      branch block) putting this in the perspective of selection of most appropriate
      pacing site in cardiac resynchronization therapy (CRT) patients. Furthermore,
      recent comparative data of epicardial and endocardial pacing have been discussed.
      There is little doubt that invasive mapping will continue to contribute in a
      substantial manner to progresses in CRT especially in the new era of endocardial
      pacing. Therefore, it is possible to envision that endocardial mapping may serve
      to selectively target the most adequate positions for the left ventricular lead
      in order to optimize CRT.

PMID- 19861391
TI  - Why, how and when do we need to optimize the setting of cardiac resynchronization
      therapy?
AB  - Current cardiac resynchronization therapy (CRT) devices allow manipulation of the
      atrioventricular (AV) and interventricular (VV) timings in order to maximize the
      left ventricular (LV) performance. Multiple echocardiographic and non
      echocardiographic methods have been proposed to optimize AV and VV intervals but
      no consensus has been reached on which methodology should preferably be used.
      Furthermore, different physiologic conditions, such as rest and exercise, may
      markedly change LV loading conditions, and therefore an optimal setting
      determined at rest may be different during exercise. The present article reviews
      current methodologies to optimize AV and VV interval and discuss why, when and
      how optimization of these delays may be performed based on current evidence.
      Moreover, an overview of the results of the multicenter trials on AV and VV
      intervals optimization is provided.

PMID- 19861393
TI  - Problems and troubleshooting in regular follow-up of patients with cardiac
      resynchronization therapy.
AB  - Biventricular pacing is an efficient treatment to improve symptoms and clinical
      outcome in patients with drug-refractory heart failure, low left ventricular
      ejection fraction and wide QRS. The basis of the treatment is the permanent
      delivery of biventricular pacing. During the follow-up of biventricular devices
      the assessment of permanent biventricular capture is fundamental. This requires a
      tailored programming with respect to the patient's activity and age, and thus
      also careful evaluations during an exercise test as well as adequate programming
      in case of cardiac arrhythmias.

PMID- 19861394
TI  - Cardiac resynchronization therapy in mild heart failure.
AB  - It has been firmly established that cardiac resynchronization therapy (CRT)
      reduces symptoms and improves mortality in patients with moderate-to-severe
      chronic heart failure [New York Heart Association (NYHA) class III-IV], despite
      optimal heart failure medication and with wide QRS complex on the surface
      electrocardiogram as evidence of ventricular dyssynchrony, but not whether such
      treatment is efficacious in mildly symptomatic heart failure patients. In such
      patients, the treatment goal is to prevent disease progression rather than to
      improve symptoms. The REVERSE trial was the first randomized, controlled study of
      CRT in NYHA I-II patients. Cardiac resynchronization therapy in this study
      induced substantial reverse remodelling over 12-18-24 months of follow-up and was
      linked to a significant delay in the time to first heart failure hospitalization
      and eventually in the time to the combined endpoint of time to first heart
      failure hospitalization or death. The MADIT CRT designed as a morbidity-mortality
      study corroborated these findings with a significant reduction in heart failure
      events and significant reverse remodelling. These findings most likely will
      translate into a wider use of CRT in mildly symptomatic patients to prevent
      disease progression.

PMID- 19861392
TI  - What is treatment success in cardiac resynchronization therapy?
AB  - Cardiac resynchronization therapy (CRT) is an established treatment for
      symptomatic patients with heart failure, a prolonged QRS duration, and impaired
      left ventricular (LV) function. Identification of 'responders' and 'non
      responders' to CRT has attracted considerable attention. The response to CRT can
      be measured in terms of symptomatic response or clinical outcome, or both.
      Alternatively, the response to CRT can be measured in terms of changes in
      surrogate measures of outcome, such as LV volumes, LV ejection fraction, invasive
      measures of cardiac performance, peak oxygen uptake, and neurohormones. This
      review explores whether these measures can be used in assessing the symptomatic
      and prognostic response to CRT. The role of these parameters to the management of
      individual patients is also discussed.

PMID- 19861395
TI  - Biventricular pacing in paced patients with normal hearts.
AB  - Right ventricular apical (RVA) stimulation, although beneficial in the treatment
      of symptomatic bradycardia, has proven detrimental in a substantial percentage of
      pacemaker recipients, leading to iatrogenic deterioration of left ventricular
      structure and function. Alternative right ventricular pacing sites appeared
      advantageous but their superiority has not been proven. Biventricular stimulation
      is effective in reducing ventricular dyssynchrony in subgroups of heart failure
      patients, improving their functional capacity, morbidity, and mortality.
      Therefore, it seems logical that this pacing strategy, by eliminating ventricular
      dyssynchrony, could play an important role in preventing the deleterious effects
      of chronic RVA stimulation in patients with normal hearts who undergo cardiac
      pacing for bradycardia indications. Preliminary investigations have yielded
      encouraging results, but further studies with harder endpoints such as quality of
      life, morbidity, and mortality are necessary to clarify the potentially
      advantageous effect of biventricular stimulation in paced patients with normal
      hearts.

PMID- 19861397
TI  - Cardiac resynchronization therapy in combination with implantable cardioverter
      defibrillator.
AB  - Device therapy for heart failure has a spectacular development during the last 10
      years. Patients with chronic heart failure might benefit from electrical therapy
      with a view to: (i) resynchronize the failing and dyssynchronized heart and
      improve its mechanical performance or (ii) prevent the risk of sudden death by
      automatic defibrillation. These two therapies can be applied together with a
      combined device, the biventricular implantable cardioverter-defibrillator (CRT
      D). Today, the proportion of CRT-D devices among all CRT devices implanted around
      the world is more than 75% and more than 85% in the USA. This review article will
      try to answer some important questions for clinical practice: is the growing use
      of CRT-D devices supported by clinical evidence? Is the risk-benefit profile of
      CRT-D favourable in particular in mildly symptomatic patients?

PMID- 19861396
TI  - Cardiac resynchronization therapy in heart failure patients with atrial
      fibrillation.
AB  - Cardiac resynchronization therapy (CRT) is an important device-based, non
      pharmacological approach that has shown, in large randomized trials, to improve
      left ventricular (LV) function and reduce both morbidity and mortality rates in
      selected patients affected by advanced heart failure (HF): New York Heart
      Association (NYHA) functional class III-IV, reduced LV systolic function with an
      ejection fraction (EF) <or=35%, QRS duration >or=120 ms, on optimal medical
      therapy, and who were in sinus rhythm. For the first time, the latest ESC and
      AHA/ACC/HRS Guidelines have considered atrial fibrillation (AF) patients, who
      constitute an important subgroup of HF patients, as eligible to receive CRT.
      Nevertheless, these Guidelines did not include a strategy for defining
      differentiated approaches according to AF duration or burden. In this review, the
      authors explain in which way AF may interfere with adequate CRT delivery, how to
      manage different AF burden, and finally present a brief overview on the effects
      of CRT in AF patients.

PMID- 19861398
TI  - Is cardiac resynchronization therapy cost-effective?
AB  - Cardiac resynchronization therapy (CRT) is a treatment of proven efficacy for
      selected patients with heart failure and associated conduction disturbances. The
      increasing financial burden that healthcare systems face has increased the
      interest in cost-effectiveness and cost-utility estimates, focused on devices
      with defibrillation capabilities (CRT-D), with a high upfront cost, as well as on
      simpler devices providing only biventricular pacing (CRT-P). Available economic
      estimates are largely dependent on data source, assumptions, modelling technique,
      time horizon, and perspective, leading to some variability in cost-effectiveness
      and cost-utility estimates. As a whole, cost-effectiveness and cost-utility
      estimates of both CRT-P and CRT-D improve as the time horizon examined is
      lengthened and appear to be below US$50,000 per quality-adjusted life-year, a
      threshold value commonly adopted for coverage of healthcare interventions in the
      USA and quite comparable with similar thresholds used within Europe. Limited data
      are available on the comparative cost-effectiveness or cost-utility of CRT-P and
      CRT-D devices. Moreover, more data on the effectiveness and long-term benefits of
      CRT-D and CRT-P are needed in order to estimate better the value of these
      treatments in the 'real world, as well as for attempts to improve cost
      effectiveness through improved patient selection.

PMID- 19861399
TI  - Topology of 4-Pyridoxic acid dehydrogenase in transformed Escherichia coli cells.
AB  - The topology of 4-pyridoxic acid dehydrogenase in the Escherichia coli cell
      membrane was examined with transformed E. coli cells overexpressing the enzyme
      from Mesorhizobium loti. The recombinant enzymes with a His(6)-tag either in the
      N-terminal region or at the C-terminus were localized on the E. coli cell
      membrane like the wild-type enzyme without a His(6)-tag. The His(6)-tags were
      labelled with Ni-NTA AP conjugate only when the E. coli protoplast cells were
      broken. The membrane-bound enzyme in the intact protoplast cells was not digested
      by trypsin, although the one in the gently broken protoplast cells was almost
      totally digested. Thus, 4-pyridoxic acid dehydrogenase was an integral monotopic
      protein, protruding into a cytoplasm side from the bacterial membrane. The
      deletion or mutation of a deduced transmembrane segment in 4-pyridoxic acid
      dehydrogenase made it an inclusion body, and the enzyme protein was not found in
      the E. coli cell membrane. Thus, it was suggested that the intact deduced
      transmembrane segment was necessary for 4-pyridoxic acid dehydrogenase to be
      localized on the bacterial cell membrane.

PMID- 19861400
TI  - Signalling pathways in the unfolded protein response: development from yeast to
      mammals.
AB  - The accumulation of unfolded proteins in the endoplasmic reticulum (ER) under ER
      stress conditions activates a series of homoeostatic responses collectively
      termed the unfolded protein response (UPR). The UPR is unique in which the
      molecular mechanisms it uses to transmit signals from the ER lumen to the nucleus
      are completely different to those used for signalling from the plasma membrane.
      An ER stress signal is sensed and transmitted across the membrane by a
      transmembrane protein(s) in the ER. Interestingly, the number of such functional
      sensors/transducers, ubiquitously expressed, has increased with evolution, for
      example, one in Saccharomyces cerevisiae, two in Caenorhabditis elegans and
      Drosophila melanogaster, and three in mammals. Accordingly, mammalian cells are
      able to cope with ER stress in a more sophisticated manner. Here, I summarize the
      mechanisms and activation consequences of UPR signalling pathways in yeast, worm,
      fly and mammalian cells. I also discuss how they have evolved to counteract ER
      stress effectively.

PMID- 19861401
TI  - Neutralization of toxic haem by Porphyromonas gingivalis haemoglobin receptor.
AB  - Free haem is known to be toxic to organs, tissues and cells. It enhances
      permeability by binding to a cell membrane, which leads to cell death, and
      damages lipids, proteins and DNA through the generation of reactive oxygen
      species. Lysine- and arginine-specific gingipains (Kgp and RgpA/B) are major
      proteinases that play an important role in the pathogenicity of a black-pigmented
      periodontopathogen named Porphyromonas gingivalis. One of the adhesin domains of
      gingipain, HbR could bind haem as an iron nutrient source for P. gingivalis.
      Using erythrocyte and its membrane as a model, results from the present study
      demonstrate that recombinant HbR expressed in Escherichia coli could inhibit haem
      induced haemolysis, probably through removing haem from the haem-membrane complex
      and lowering free haem toxicity by mediating dimerization of haem molecules. The
      ability to protect a cell membrane from haem toxicity is a new function for HbR.

PMID- 19861402
TI  - Education reduces the effects of genetic susceptibilities to poor physical
      health.
AB  - BACKGROUND: Greater education is associated with better physical health. This has
      been of great concern to public health officials. Most demonstrations show that
      education influences mean levels of health. Little is known about the influence
      of education on variance in health status, or about how this influence may impact
      the underlying genetic and environmental sources of health problems. This study
      explored these influences. METHODS: In a 2002 postal questionnaire, 21 522
      members of same-sex pairs in the Danish Twin Registry born between 1931 and 1982
      reported physical health in the 12-item Short Form Health Survey. We used
      quantitative genetic models to examine how genetic and environmental variance in
      physical health differed with level of education, adjusting for birth-year
      effects. RESULTS: and Conclusions As expected, greater education was associated
      with better physical health. Greater education was also associated with smaller
      variance in health status. In both sexes, 2 standard deviations (SDs) above mean
      educational level, variance in physical health was only about half that among
      those 2 SDs below. This was because fewer highly educated people reported poor
      health. There was less total variance in health primarily because there was less
      genetic variance. Education apparently reduced expression of genetic
      susceptibilities to poor health. The patterns of genetic and environmental
      correlations suggested that this might take place because more educated people
      manage their environments to protect their health. If so, fostering the personal
      charactieristics associated with educational attainment could be important in
      reducing the education-health gradient.

PMID- 19861403
TI  - D-cycloserine into the BLA reverses the impairing effects of exposure to stress
      on the extinction of contextual fear, but not conditioned taste aversion.
AB  - We investigated whether the N-methyl-D-aspartate (NMDA) receptor partial agonist
      D-cycloserine (DCS, 20 microg/side) microinfused into the basolateral amygdala
      (BLA) would reverse stress-induced impairment of extinction in two aversive
      learning paradigms: contextual fear conditioning and conditioned taste aversion
      (CTA). We found that DCS in the BLA show differential involvement in the
      extinction of these two paradigms and in its modulation of stress-induced
      impairment of extinction. This may suggest that the dysfunctional extinction of
      fear and taste aversion following exposure to a stressful experience may be
      modulated by different mechanisms.

PMID- 19861404
TI  - z-Leucinyl-leucinyl-norleucinal induces apoptosis of human glioblastoma tumor
      initiating cells by proteasome inhibition and mitotic arrest response.
AB  - Gamma-secretase inhibitors have been proposed as drugs able to kill cancer cells
      by targeting the NOTCH pathway. Here, we investigated two of such inhibitors, the
      Benzyloxicarbonyl-Leu-Leu-Nle-CHO (LLNle) and the N-[N-(3,5-difluorophenacetyl)-L
      alanyl]-S-phenylglycine t-butyl ester (DAPT), to assess whether they were
      effective in killing human glioblastoma tumor-initiating cells (GBM TIC) in
      vitro. We found that only LLNle was able at the micromolar range to induce the
      death of GBM TICs by apoptosis. To determine the cellular processes that were
      activated in GBM TICs by treatment with LLNle, we analyzed the amount of the
      NOTCH intracellular domain and the gene expression profiles following treatment
      with LLNle, DAPT, and DMSO (vehicle). We found that LLNIe, beside inhibiting the
      generation of the NOTCH intracellular domain, also induces proteasome inhibition,
      proteolytic stress, and mitotic arrest in these cells by repressing genes
      required for DNA synthesis and mitotic progression and by activating genes acting
      as mitotic inhibitors. DNA content flow cytometry clearly showed that cells
      treated with LLNle undergo arrest in the G(2)-M phases of the cell cycle. We also
      found that DAPT and L-685,458, another selective Notch inhibitor, were unable to
      kill GBM TICs, whereas lactacystin, a pure proteasome inhibitor, was effective
      although at a much less extent than LLNle. These data show that LLNle kills GBM
      TIC cells by inhibiting the proteasome activity. We suggest that LLNle, being
      able to target two relevant pathways for GBM TIC survival, may have a potential
      therapeutic value that deserves further investigation in animal models.

PMID- 19861405
TI  - RhoC expression and head and neck cancer metastasis.
AB  - RhoC protein, a known marker of metastases in aggressive breast cancers and
      melanoma, has also been found to be overexpressed in certain head and neck
      cancers, thus we investigated the correlation between RhoC expression and the
      metastatic behavior of head and neck squamous cell carcinoma. Selective
      inhibition of RhoC expression was achieved using lentiviral small hairpin RNA
      (shRNA) transduced and tracked with green fluorescent protein to achieve 70% to
      80% RhoC inhibition. Fluorescence microscopy of the RhoC knockdown stable clones
      showed strong green fluorescence in the majority of cells, signifying a high
      efficiency of transduction. Importantly, quantitative real-time PCR showed no
      significant decrease in the mRNA expression levels of other members of the Ras
      superfamily. Cell motility and invasion were markedly diminished in RhoC-depleted
      cell lines as compared with control transduced lines. H&E staining of lung tissue
      obtained from severe combined immunodeficiency mice, which had been implanted
      with RhoC knockdown cells, showed a marked decrease in lung metastasis and
      inflammation of the blood vessels. The cultured lung tissue showed a significant
      decrease in cell growth in mice implanted with RhoC-depleted cell lines as
      compared with shRNA-scrambled sequence control lines. Microscopic studies of CD31
      expression revealed substantial quantitative and qualitative differences in the
      primary tumor microvessel density as compared with parental and shRNA-scrambled
      controls. This study is the first of its kind to establish the involvement of
      RhoC specifically in head and neck metastasis. These findings suggest that RhoC
      warrants further investigation to delineate its robustness as a novel potentially
      therapeutic target.

PMID- 19861406
TI  - Tumor necrosis factor-like weak inducer of apoptosis stimulation of glioma cell
      survival is dependent on Akt2 function.
AB  - Malignant gliomas are the most common primary brain tumors. Despite intensive
      clinical investigation and significant technical advances in surgical and
      radiation treatment, the impact on clinical outcome for patients with malignant
      gliomas is disappointing. We have previously shown that tumor necrosis factor
      like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor
      superfamily, can stimulate glioma cell survival via binding to the Fn14 receptor,
      activation of the NF-kappaB pathway, and upregulation of BCL-X(L) gene
      expression. Here, we show that TWEAK treatment of glioma cells leads to
      phosphorylation of Akt and BAD. TWEAK stimulation results in the phosphorylation
      of both Akt1 and Akt2. However, small interfering RNA (siRNA)-mediated depletion
      of either Akt1 or Akt2 showed that BAD serine 136 phosphorylation is dependent
      specifically on Akt2 function. Depletion of Akt2 expression by siRNA also
      abrogates TWEAK-stimulated glioma cell survival, whereas no effect on glioma cell
      survival was observed after siRNA-mediated depletion of Akt1 expression.
      Surprisingly, although siRNA-mediated depletion of BAD in glioma cells abrogates
      cytotoxic- and chemotherapy-induced apoptosis, TWEAK still displays a strong
      protective effect, suggesting that BAD serine 136 phosphorylation plays a minor
      role in TWEAK-Akt2-induced glioma cell survival. We also report here that AKT2
      gene expression levels increased with glioma grade and inversely correlate with
      patient survival. Additionally, immunohistochemical analysis showed that Akt2
      expression positively correlates with Fn14 expression in glioblastoma multiforme
      specimens. We hypothesize that the TWEAK-Fn14 signaling axis functions, in part,
      to enhance glioblastoma cell survival by activation of the Akt2 serine/threonine
      protein kinase.

PMID- 19861407
TI  - Estrogenic promotion of ErbB2 tyrosine kinase activity in mammary tumor cells
      requires activation of ErbB3 signaling.
AB  - Increasing evidence suggests molecular interactions between erbB2 and other
      receptor tyrosine kinases, and estrogenic compounds and their cognate receptors.
      We have recently reported that downregulation of erbB3 abrogates erbB2-mediated
      tamoxifen resistance in breast cancer cells. On the basis of these data, we
      hypothesized that erbB3 may play a major role connecting these two sentinel
      pathways. Interactions were studied using mammary/breast cancer cell lines from
      wild-type rat c-neu gene transgenic mice and humans. Estradiol promoted cell
      proliferation and activated erbB2/neu tyrosine kinase, Akt, and mitogen-activated
      protein kinase signaling exclusively in mammary and breast epithelial cell lines
      with coexpression of both erbB2 and erbB3. Estradiol action was independent of
      the transgene promoter (MMTV-LTR) activity, both in vitro and in vivo, as well as
      c-neu transgene or endogenous erbB2 gene expression. Estrogen induction of cell
      growth promotion, erbB2/neu activation, and downstream signaling was abrogated by
      blockade of estrogen receptor (ER) with the pure ER antagonist ICI 182,780 or
      knockdown of erbB3 expression via specific siRNA. These data suggest that
      activation of both ER and erbB2/erbB3 signaling is requisite for estrogen-induced
      mitogenesis and erbB2/neu tyrosine kinase activation.

PMID- 19861408
TI  - Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in
      mouse models and human cell lines.
AB  - We recently identified the secreted protein IGFBP7 as a factor required for an
      activated BRAF oncogene to induce senescence or apoptosis in primary human cells.
      In human melanomas containing an activating BRAF mutation (BRAF-positive
      melanomas), IGFBP7 is epigenetically silenced, which seems to be a critical step
      in melanoma genesis. Restoration of IGFBP7 function by the addition of
      recombinant IGFBP7 (rIGFBP7) induces apoptosis in BRAF-positive human melanoma
      cell lines, and systemically administered rIGFBP7 markedly suppresses the growth
      of BRAF-positive primary tumors in xenografted mice. Here we further evaluate the
      role of IGFBP7 in the treatment of BRAF-positive melanoma and other malignancies.
      We find that in human metastatic melanoma samples IGFBP7 is epigenetically
      silenced and at an even higher frequency than that found in primary melanomas.
      Using a murine experimental metastasis assay, we show that systemic
      administration of rIGFBP7 markedly suppresses the growth of metastatic disease
      and prolongs survival. An analysis of the NCI60 panel of human cancer cell lines
      reveals that in addition to melanoma, IGFBP7 induces apoptosis in several other
      cancer types, in particular colorectal cancer cell lines. In general, IGFBP7
      induces apoptosis in human cancer cell lines that have an activating mutation in
      BRAF or RAS, and that are sensitive to chemical inhibition of BRAF-MEK-ERK
      signaling. Significantly, systemically administered rIGFBP7 blocks the growth of
      colorectal tumors containing an activating RAS or BRAF mutation in mouse
      xenografts. The results presented here, in conjunction with those from previous
      studies, justify the further development of IGFBP7 as an anticancer agent.

PMID- 19861409
TI  - Effects of Src kinase inhibition induced by dasatinib in non-small cell lung
      cancer cell lines treated with cisplatin.
AB  - c-Src is a tyrosine kinase involved in tumor proliferation, migration, and
      angiogenesis and has been shown to modulate the cytotoxicity following cisplatin
      induced DNA damages. c-Src is frequently activated in non-small cell lung cancer
      (NSCLC) tissues and cell lines, but no preclinical data regarding the effects of
      the novel potent Src inhibitor, dasatinib (BMS-354825), in the modulation of
      cisplatin resistance are currently available. The present study reports that
      treatment with dasatinib completely abrogated Src phosphorylation in the majority
      of the NSCLC cell lines tested (n = 7), with modest effects on cell proliferation
      and survival. In five cell lines, a higher cytotoxicity was observed delivering
      cisplatin in combination with dasatinib: the most evident effects were found in
      the squamous H520 cells due to the effective block of cisplatin-induced Src
      phosphorylation. Moreover, dasatinib treatment significantly blocked cisplatin
      induced transcription of a panel of DNA repair and synthesis genes. In addition,
      a real-time PCR analysis done on tumor and matched normal lung specimens from 44
      surgically resected NSCLC patients showed that Src transcripts are significantly
      upregulated in 23% of cases. In conclusion, Src-directed therapeutic strategies
      could interfere with cisplatin resistance, possibly allowing to reduce cisplatin
      doses, thus improving its efficacy. The data of this study support further
      clinical studies aimed to evaluate the efficacy of Src-inhibiting agents in
      combination with cisplatin in the treatment of NSCLC.

PMID- 19861410
TI  - Lack of oxygen deactivates mitochondrial complex I: implications for ischemic
      injury?
AB  - For S-nitrosothiols and peroxynitrite to interfere with the activity of
      mitochondrial complex I, prior transition of the enzyme from its active (A) to
      its deactive, dormant (D) state is necessary. We now demonstrate accumulation of
      the D-form of complex I in human epithelial kidney cells after prolonged hypoxia.
      Upon reoxygenation after hypoxia there was an initial delay in the return of the
      respiration rate to normal. This was due to the accumulation of the D-form and
      its slow, substrate-dependent reconversion to the A-form. Reconversion to the A
      form could be prevented by prolonged incubation with endogenously generated NO.
      We propose that the hypoxic transition from the A-form to the D-form of complex I
      may be protective, because it would act to reduce the electron burst and the
      formation of free radicals during reoxygenation. However, this may become an
      early pathophysiological event when NO-dependent formation of S-nitrosothiols or
      peroxynitrite structurally modifies complex I in its D-form and impedes its
      return to the active state. These observations provide a mechanism to account for
      the severe cell injury that follows hypoxia and reoxygenation when accompanied by
      NO generation.

PMID- 19861411
TI  - Tissue-specific short chain fatty acid metabolism and slow metabolic recovery
      after ischemia from hyperpolarized NMR in vivo.
AB  - Mechanistic details of mammalian metabolism in vivo and dynamic metabolic changes
      in intact organisms are difficult to monitor because of the lack of spatial,
      chemical, or temporal resolution when applying traditional analytical tools.
      These limitations can be addressed by sensitivity enhancement technology for fast
      in vivo NMR assays of enzymatic fluxes in tissues of interest. We apply this
      methodology to characterize organ-specific short chain fatty acid metabolism and
      the changes of carnitine and coenzyme A pools in ischemia reperfusion. This is
      achieved by assaying acetyl-CoA synthetase and acetyl-carnitine transferase
      catalyzed transformations in vivo. The fast and predominant flux of acetate and
      propionate signal into acyl-carnitine pools shows the efficient buffering of free
      CoA levels. Sizeable acetyl-carnitine formation from exogenous acetate is even
      found in liver, where acetyl-CoA synthetase and acetyl-carnitine transferase
      activities have been assumed sequestered in different compartments. In vivo
      assays of altered acetate metabolism were applied to characterize pathological
      changes of acetate metabolism upon ischemia. Coenzyme pools in ischemic skeletal
      muscle are reduced in vivo even 1 h after disturbing muscle perfusion. Impaired
      mitochondrial metabolism and slow restoration of free CoA are corroborated by
      assays employing fumarate to show persistently reduced tricarboxylic acid (TCA)
      cycle activity upon ischemia. In the same animal model, anaerobic metabolism of
      pyruvate and tissue perfusion normalize faster than mitochondrial bioenergetics.

PMID- 19861412
TI  - Chaperokine function of recombinant Hsp72 produced in insect cells using a
      baculovirus expression system is retained.
AB  - Extracellular heat shock protein 72 (Hsp72; inducible form of the 70-kDa heat
      shock protein) plays a critical role in innate and adaptive immune responses and
      has shown promise as an ideal adjuvant for the optimization of antigen-specific
      anti-tumor vaccines. Recent studies suggest that to correctly elucidate the
      mechanisms by which Hsp72 exerts its beneficial effects in vitro, great care must
      be taken to ensure that endotoxin by-products do not invalidate the findings. In
      this study, we have taken advantage of the baculovirus expression vector system
      for production of endotoxin-free recombinant Hsp72. The coding sequence of human
      hsp72 was recombined into the baculovirus immediately downstream of the strong
      polyhedron gene promoter. Ninety-six h post-infection of Sf9 insect cells with
      recombinant baculovirus, maximal levels of Hsp72 protein were detected. The
      recombinant human Hsp72 was purified by affinity chromatography from insect
      cells, and purity was confirmed by SDS-PAGE and mass spectrometry. The purified
      human recombinant Hsp72(bv) (Hsp72 produced using the BEVS) was demonstrated to
      have no endotoxin contamination and was shown to have stimulated potent calcium
      flux in the human monocytic cell line. Furthermore, recombinant Hsp72(bv)
      enhanced the tolerance of neuroblastoma cells to heat stress-induced cell death
      and displayed classical chaperokine functions including augmentation of
      inflammatory cytokine productions in mouse splenocytes. The production of
      functional, endotoxin-free recombinant human Hsp72(bv) in insect cells is
      inexpensive and convenient and eliminates the need of special procedures for
      endotoxin depletion. Endotoxin-free recombinant human Hsp72(bv) can now be used
      to unlock the important role Hsp72 plays in modulating immune function.

PMID- 19861413
TI  - Mapping of disulfide bonds within the amino-terminal extracellular domain of the
      inhibitory glycine receptor.
AB  - The strychnine-sensitive glycine receptor (GlyR) is a ligand-gated chloride
      channel and a member of the superfamily of cysteine loop (Cys-loop)
      neurotransmitter receptors, which also comprises the nicotinic acetylcholine
      receptor (nAChR). Within the extracellular domain (ECD), the eponymous Cys-loop
      harbors two conserved cysteines, assumed to be linked by a superfamily-specific
      disulfide bond. The GlyR ECD carries three additional cysteine residues, two are
      predicted to form a second, GlyR-specific bond. The configuration of none of the
      cysteines of GlyR, however, had been determined directly. Based on a crystal
      structure of the nAChRalpha1 ECD, we generated a model of the human GlyRalpha1
      where close proximity of the respective cysteines was consistent with the
      formation of both the Cys-loop and the GlyR-specific disulfide bonds. To identify
      native disulfide bonds, the GlyRalpha1 ECD was heterologously expressed and
      refolded under oxidative conditions. By matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry, we detected tryptic fragments of the
      ECD indicative of disulfide bond formation for both pairs of cysteines, as
      proposed by modeling. The identity of tryptic fragments was confirmed using
      chemical modification of cysteine and lysine residues. As evident from circular
      dichroism spectroscopy, mutagenesis of single cysteines did not impair refolding
      of the ECD in vitro, whereas it led to partial or complete intracellular
      retention and consequently to a loss of function of full-length GlyR subunits in
      human embryonic kidney 293 cells. Our results indicate that the GlyR ECD forms
      both a Cys-loop and a GlyR-specific disulfide bond. In addition, cysteine
      residues appear to be important for protein maturation in vivo.

PMID- 19861414
TI  - Cannabinoid 1 receptor and interleukin-6 receptor together induce integration of
      protein kinase and transcription factor signaling to trigger neurite outgrowth.
AB  - Activation of the G(o/i)-coupled cannabinoid 1 receptor (CB1R) has been shown to
      induce neurite outgrowth in Neuro2A cells through activation of Src kinase and
      STAT3 transcription factor. Signaling by the interleukin 6 receptor (IL-6R) also
      activates STAT3 through Jak kinase. We studied if signals from the two pathways
      could be integrated in a synergistic manner to trigger neurite outgrowth in
      Neuro2A cells. At low concentrations, when agonist at either receptor by itself
      has no effect, we found that CB1R and IL-6R stimulation together induced
      synergistic neurite outgrowth. Signal integration requires activation of
      transcription factors by Src, Jak, and mitogen-activated protein kinases. Mitogen
      activated protein kinase can be activated by both receptors and shows enhanced
      early activation in the presence of both ligands. CREB and STAT3 transcription
      factors are required for synergy and show enhanced DNA-binding activity when both
      receptors are activated. STAT3 plays a critical role in integration of the
      signals downstream of the two receptors. When both pathways are activated, STAT3
      phosphorylation is sustained for 6 h. This prolonged activation of STAT3 requires
      deactivation of SHP2 phosphatase. Reduction of SHP2 levels by RNA interference
      results in greater synergy in neurite outgrowth. Simultaneous knockdown of both
      SHP2 and STAT3 blocks the synergistic triggering of neurite outgrowth, indicating
      that STAT3 is downstream of SHP2. CB1R and IL-6R co-stimulation enhanced the
      differentiation of rat cortical neuron primary cultures. These results provide a
      mechanism where multiple protein kinases and transcription factors interact to
      integrate signals from G protein-coupled and cytokine receptor to evoke neurite
      outgrowth in Neuro2A cells.

PMID- 19861415
TI  - Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP
      response element-binding protein phosphorylation and increased PGC-1alpha
      expression.
AB  - Bioactive compounds reported to stimulate mitochondrial biogenesis are linked to
      many health benefits such increased longevity, improved energy utilization, and
      protection from reactive oxygen species. Previously studies have shown that mice
      and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced
      mitochondrial content. Therefore, we hypothesized that PQQ can induce
      mitochondrial biogenesis in mouse hepatocytes. Exposure of mouse Hepa1-6 cells to
      10-30 microm PQQ for 24-48 h resulted in increased citrate synthase and
      cytochrome c oxidase activity, Mitotracker staining, mitochondrial DNA content,
      and cellular oxygen respiration. The induction of this process occurred through
      the activation of cAMP response element-binding protein (CREB) and peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a pathway
      known to regulate mitochondrial biogenesis. PQQ exposure stimulated
      phosphorylation of CREB at serine 133, activated the promoter of PGC-1alpha, and
      increased PGC-1alpha mRNA and protein expression. PQQ did not stimulate
      mitochondrial biogenesis after small interfering RNA-mediated reduction in either
      PGC-1alpha or CREB expression. Consistent with activation of the PGC-1alpha
      pathway, PQQ increased nuclear respiratory factor activation (NRF-1 and NRF-2)
      and Tfam, TFB1M, and TFB2M mRNA expression. Moreover, PQQ protected cells from
      mitochondrial inhibition by rotenone, 3-nitropropionic acid, antimycin A, and
      sodium azide. The ability of PQQ to stimulate mitochondrial biogenesis accounts
      in part for action of this compound and suggests that PQQ may be beneficial in
      diseases associated with mitochondrial dysfunction.

PMID- 19861416
TI  - Novel nuclear nesprin-2 variants tether active extracellular signal-regulated
      MAPK1 and MAPK2 at promyelocytic leukemia protein nuclear bodies and act to
      regulate smooth muscle cell proliferation.
AB  - Nuclear and cytoplasmic scaffold proteins have been shown to be essential for
      temporal and spatial organization, as well as the fidelity, of MAPK signaling
      pathways. In this study we show that nesprin-2 is a novel extracellular signal
      regulated MAPK1 and 2 (ERK1/2) scaffold protein that serves to regulate nuclear
      signaling by tethering these kinases at promyelocytic leukemia protein nuclear
      bodies (PML NBs). Using immunofluorescence microscopy, GST pull-down and
      immunoprecipitation, we show that nesprin-2, ERK1/2, and PML colocalize and bind
      to form a nuclear complex. Interference of nesprin-2 function, by either siRNA
      mediated knockdown or overexpression of a dominant negative nesprin-2 fragment,
      augmented ERK1/2 nuclear signaling shown by increased SP1 activity and ELK1
      phosphorylation. The functional outcome of nesprin-2 disruption and the resultant
      sustained ERK1/2 signal was increased proliferation. Importantly, these
      activities were not induced by previously identified nuclear envelope (NE)
      targeted nesprin-2 isoforms but rather were mediated by novel nuclear isoforms
      that lacked the KASH domain. Taken together, this study suggests that nesprin-2
      is a novel intranuclear scaffold, essential for nuclear ERK1/2 signaling fidelity
      and cell cycle progression.

PMID- 19861417
TI  - Hepatitis C virus impairs p53 via persistent overexpression of 3beta
      hydroxysterol Delta24-reductase.
AB  - Persistent infection with hepatitis C virus (HCV) induces tumorigenicity in
      hepatocytes. To gain insight into the mechanisms underlying this process, we
      generated monoclonal antibodies on a genome-wide scale against an HCV-expressing
      human hepatoblastoma-derived cell line, RzM6-LC, showing augmented
      tumorigenicity. We identified 3beta-hydroxysterol Delta24-reductase (DHCR24) from
      this screen and showed that its expression reflected tumorigenicity. HCV induced
      the DHCR24 overexpression in human hepatocytes. Ectopic or HCV-induced DHCR24
      overexpression resulted in resistance to oxidative stress-induced apoptosis and
      suppressed p53 activity. DHCR24 overexpression in these cells paralleled the
      increased interaction between p53 and MDM2 (also known as HDM2), a p53-specific
      E3 ubiquitin ligase, in the cytoplasm. Persistent DHCR24 overexpression did not
      alter the phosphorylation status of p53 but resulted in decreased acetylation of
      p53 at lysine residues 373 and 382 in the nucleus after treatment with hydrogen
      peroxide. Taken together, these results suggest that DHCR24 is elevated in
      response to HCV infection and inhibits the p53 stress response by stimulating the
      accumulation of the MDM2-p53 complex in the cytoplasm and by inhibiting the
      acetylation of p53 in the nucleus.

PMID- 19861418
TI  - Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis
      in type 2 diabetes.
AB  - The islet in type 2 diabetes (T2DM) and the brain in neurodegenerative diseases
      share progressive cell dysfunction, increased apoptosis, and accumulation of
      locally expressed amyloidogenic proteins (islet amyloid polypeptide (IAPP) in
      T2DM). Excessive activation of the Ca(2+)-sensitive protease calpain-2 has been
      implicated as a mediator of oligomer-induced cell death and dysfunction in
      neurodegenerative diseases. To establish if human IAPP toxicity is mediated by a
      comparable mechanism, we overexpressed human IAPP in rat insulinoma cells and
      freshly isolated human islets. Pancreas was also obtained at autopsy from humans
      with T2DM and nondiabetic controls. We report that overexpression of human IAPP
      leads to the formation of toxic oligomers and increases beta cell apoptosis
      mediated by increased cytosolic Ca(2+) and hyperactivation of calpain-2. Cleavage
      of alpha-spectrin, a marker of calpain hyperactivation, is increased in beta
      cells in T2DM. We conclude that overactivation of Ca(2+)-calpain pathways
      contributes to beta cell dysfunction and apoptosis in T2DM.

PMID- 19861420
TI  - Structural features of the tmRNA-ribosome interaction.
AB  - Trans-translation is a process which switches the synthesis of a polypeptide
      chain encoded by a nonstop messenger RNA to the mRNA-like domain of a transfer
      messenger RNA (tmRNA). It is used in bacterial cells for rescuing the ribosomes
      arrested during translation of damaged mRNA and directing this mRNA and the
      product polypeptide for degradation. The molecular basis of this process is not
      well understood. Earlier, we developed an approach that allowed isolation of
      tmRNA-ribosomal complexes arrested at a desired step of tmRNA passage through the
      ribosome. We have here exploited it to examine the tmRNA structure using chemical
      probing and cryo-electron microscopy tomography. Computer modeling has been used
      to develop a model for spatial organization of the tmRNA inside the ribosome at
      different stages of trans-translation.

PMID- 19861419
TI  - GRIN1 regulates micro-opioid receptor activities by tethering the receptor and G
      protein in the lipid raft.
AB  - The lipid raft location of mu-opioid receptor (MOR) determines the receptor
      activities. However, the manner in which MOR is anchored within the lipid rafts
      is undetermined. Using the targeted proteomic approach and mass spectrometry
      analyses, we have identified GRIN1 (G protein-regulated inducer of neurite
      outgrowth 1) can tether MOR with the G protein alpha-subunit and subsequently
      regulate the receptor distribution within the lipid rafts. Glutathione S
      transferase fusion pulldown and receptor mutational analyses indicate that GRIN1
      MOR interaction involves a receptor sequence (267)GSKEK(271) within the MOR third
      intracellular loop that is not involved in Galpha interaction. The GRIN1 domains
      involved in MOR interaction are also distinct from those involved in Galpha
      interaction. Pertussis toxin pretreatment reduced the amount of GRIN1 co
      immunoprecipitated with MOR but not the amount with Galpha. Furthermore,
      overexpression of GRIN1 significantly enhanced the amount of MOR in lipid raft
      and the receptor signaling magnitude as measured by Src kinase activation. Such
      increase in MOR signaling was demonstrated further by determining the GRIN1
      dependent pertussis toxin-sensitive neurite outgrowth. In contrast to minimal
      neurite outgrowth induced by etorphine in control neuroblastoma N2A cells,
      overexpression of GRIN1 resulted in the increase in etorphine- and non-morphine
      induced neurite outgrowth in these cells. Knocking down endogenous GRIN1 by small
      interfering RNA attenuated the agonist-induced neurite outgrowth. Disrupting
      lipid raft by methyl-beta-cyclodextrin also blocked neurite outgrowth. Hence, by
      tethering Galpha with MOR, GRIN1 stabilizes the receptor within the lipid rafts
      and potentiates the receptor signaling in the neurite outgrowth processes.

PMID- 19861421
TI  - The Arabidopsis thaliana double-stranded RNA binding protein DRB1 directs guide
      strand selection from microRNA duplexes.
AB  - In Arabidopsis thaliana (Arabidopsis), DICER-LIKE1 (DCL1) functions together with
      the double-stranded RNA binding protein (dsRBP), DRB1, to process microRNAs
      (miRNAs) from their precursor transcripts prior to their transfer to the RNA
      induced silencing complex (RISC). miRNA-loaded RISC directs RNA silencing of
      cognate mRNAs via ARGONAUTE1 (AGO1)-catalyzed cleavage. Short interefering RNAs
      (siRNAs) are processed from viral-derived or transgene-encoded molecules of
      double-stranded RNA (dsRNA) by the DCL/dsRBP partnership, DCL4/DRB4, and are also
      loaded to AGO1-catalyzed RISC for cleavage of complementary mRNAs. Here, we use
      an artificial miRNA (amiRNA) technology, transiently expressed in Nicotiana
      benthamiana, to produce a series of amiRNA duplexes with differing intermolecular
      thermostabilities at the 5' end of duplex strands. Analyses of amiRNA duplex
      strand accumulation and target transcript expression revealed that strand
      selection (amiRNA and amiRNA*) is directed by asymmetric thermostability of the
      duplex termini. The duplex strand possessing a lower 5' thermostability was
      preferentially retained by RISC to guide mRNA cleavage of the corresponding
      target transgene. In addition, analysis of endogenous miRNA duplex strand
      accumulation in Arabidopsis drb1 and drb2345 mutant plants revealed that DRB1
      dictates strand selection, presumably by directional loading of the miRNA duplex
      onto RISC for passenger strand degradation. Bioinformatic and Northern blot
      analyses of DCL4/DRB4-dependent small RNAs (miRNAs and siRNAs) revealed that
      small RNAs produced by this DCL/dsRBP combination do not conform to the same
      terminal thermostability rules as those governing DCL1/DRB1-processed miRNAs.
      This suggests that small RNA processing in the DCL1/DRB1-directed miRNA and
      DCL4/DRB4-directed sRNA biogenesis pathways operates via different mechanisms.

PMID- 19861422
TI  - The tedious task of finding homologous noncoding RNA genes.
AB  - User-driven in silico RNA homology search is still a nontrivial task. In part,
      this is the consequence of a limited precision of the computational tools in
      spite of recent exciting progress in this area, and to a certain extent,
      computational costs are still problematic in practice. An important, and as we
      argue here, dominating issue is the dependence on good curated (secondary)
      structural alignments of the RNAs. These are often hard to obtain, not so much
      because of an inherent limitation in the available data, but because they require
      substantial manual curation, an effort that is rarely acknowledged. Here, we
      qualitatively describe a realistic scenario for what a "regular user" (i.e., a
      nonexpert in a particular RNA family) can do in practice, and what kind of
      results are likely to be achieved. Despite the indisputable advances in
      computational RNA biology, the conclusion is discouraging: BLAST still works
      better or equally good as other methods unless extensive expert knowledge on the
      RNA family is included. However, when good curated data are available the recent
      development yields further improvements in finding remote homologs. Homology
      search beyond the reach of BLAST hence is not at all a routine task.

PMID- 19861423
TI  - Free energy calculation of modified base-pair formation in explicit solvent: A
      predictive model.
AB  - The maturation of RNAs includes site-specific post-transcriptional modifications
      that contribute significantly to hydrogen bond formation within RNA and between
      different RNAs, especially in formation of mismatch base pairs. Thus, an
      understanding of the geometry and strength of the base-pairing of modified
      ribonucleoside 5'-monophosphates, previously not defined, is applicable to
      investigations of RNA structure and function and of the design of novel RNAs. The
      geometry and free energies of base-pairings were calculated in aqueous solution
      under neutral conditions with AMBER force fields and molecular dynamics
      simulations (MDSs). For example, unmodified uridines were observed to bind to
      uridine and cytidine with significant stability, but the ribose C1'-C1' distances
      were far short ( approximately 8.9 A) of distances observed for canonical A-form
      RNA helices. In contrast, 5-oxyacetic acid uridine, known to bind adenosine,
      wobble to guanosine, and form mismatch base pairs with uridine and cytidine,
      bound adenosine and guanosine with geometries and energies comparable to an
      unmodified uridine. However, the 5-oxyacetic acid uridine base paired to uridine
      and cytidine with a C1'-C1' distance comparable to that of an A-form helix,
      approximately 11 A, when a H(2)O molecule migrated between and stably hydrogen
      bonded to both bases. Even in formation of canonical base pairs, intermediate
      structures with a second energy minimum consisted of transient H(2)O molecules
      forming hydrogen bonded bridges between the two bases. Thus, MDS is predictive of
      the effects of modifications, H(2)O molecule intervention in the formation of
      base-pair geometry, and energies that are important for native RNA structure and
      function.

PMID- 19861424
TI  - Transcription of the Dictyostelium discoideum mitochondrial genome occurs from a
      single initiation site.
AB  - Transcription of the mitochondrial genome in Dictyostelium discoideum gives rise
      to eight major polycistronic RNA species that can be detected by Northern
      hybridization. In order to determine whether these transcripts could possibly
      derive from processing of even larger transcripts, reverse transcriptase
      polymerase chain reactions (RT-PCRs) were performed in an attempt to amplify the
      intervening regions between the eight major transcripts. All but one intervening
      region were successfully reverse transcribed and amplified, indicating that even
      larger transcripts existed and that the eight major transcripts detected
      previously may be the products of transcript processing. Southern hybridization
      analyses of DNA fragments representing the sequences between the eight major
      transcripts with in vitro capped mitochondrial RNA identified the 5' end of only
      one of the eight major transcripts as a genuine transcription start site. The
      ability to initiate transcription from DNA sequences upstream of the identified
      transcription initiation site was demonstrated in bacterial cells expressing the
      Dictyostelium mitochondrial RNA polymerase. We conclude that transcription of the
      Dictyostelium mitochondrial genome is initiated at a single site, generating a
      large polycistronic transcript that is very efficiently, probably
      cotranscriptionally processed into mature RNA species. This is the first report
      on a protist mitochondrial DNA that is, although much larger in size than its
      metazoan counterparts, transcribed from a single transcription initiation site.

PMID- 19861425
TI  - Translation initiation complex formation in the crenarchaeon Sulfolobus
      solfataricus.
AB  - The function of initiation factors in and the sequence of events during
      translation initiation have been intensively studied in Bacteria and Eukaryotes,
      whereas in Archaea knowledge on these functions/processes is limited. By
      employing chemical probing, we show that translation initiation factor aIF1 of
      the model crenarchaeon Sulfolobus solfataricus binds to the same area on the
      ribosome as the bacterial and eukaryal orthologs. Fluorescence energy transfer
      assays (FRET) showed that aIF1, like its eukaryotic and bacterial orthologs, has
      a fidelity function in translation initiation complex formation, and that both
      aIF1 and aIF1A exert a synergistic effect in stimulating ribosomal association of
      the Met-tRNAi(Met) binding factor a/eIF2. However, as in Eukaryotes their effect
      on a/eIF2 binding appears to be indirect. Moreover, FRET was used to analyze for
      the first time the sequence of events toward translation initiation complex
      formation in an archaeal model system. These studies suggested that a/eIF2-GTP
      binds first to the ribosome and then recruits Met-tRNAi(Met), which appears to
      comply with the operational mode of bacterial IF2, and deviates from the shuttle
      function of the eukaryotic counterpart eIF2. Thus, despite the resemblance of
      eIF2 and a/eIF2, recruitment of initiator tRNA to the ribosome is mechanistically
      different in Pro- and Eukaryotes.

PMID- 19861426
TI  - Next-generation SELEX identifies sequence and structural determinants of splicing
      factor binding in human pre-mRNA sequence.
AB  - Many splicing factors interact with both mRNA and pre-mRNA. The identification of
      these interactions has been greatly improved by the development of in vivo cross
      linking immunoprecipitation. However, the output carries a strong sampling bias
      in favor of RNPs that form on more abundant RNA species like mRNA. We have
      developed a novel in vitro approach for surveying binding on pre-mRNA, without
      cross-linking or sampling bias. Briefly, this approach entails specifically
      designed oligonucleotide pools that tile through a pre-mRNA sequence. The pool is
      then partitioned into bound and unbound fractions, which are quantified by a two
      color microarray. We applied this approach to locating splicing factor binding
      sites in and around approximately 4000 exons. We also quantified the effect of
      secondary structure on binding. The method is validated by the finding that
      U1snRNP binds at the 5' splice site (5'ss) with a specificity that is nearly
      identical to the splice donor motif. In agreement with prior reports, we also
      show that U1snRNP appears to have some affinity for intronic G triplets that are
      proximal to the 5'ss. Both U1snRNP and the polypyrimidine tract binding protein
      (PTB) avoid exonic binding, and the PTB binding map shows increased enrichment at
      the polypyrimidine tract. For PTB, we confirm polypyrimidine specificity and are
      also able to identify structural determinants of PTB binding. We detect multiple
      binding motifs enriched in the PTB bound fraction of oligonucleotides. These
      motif combinations augment binding in vitro and are also enriched in the vicinity
      of exons that have been determined to be in vivo targets of PTB.

PMID- 19861427
TI  - Characterization of the functional role of nucleotides within the URE2 IRES
      element and the requirements for eIF2A-mediated repression.
AB  - Cap-independent initiation of translation is thought to promote protein synthesis
      on some mRNAs during times when cap-dependent initiation is down-regulated.
      However, the mechanism of cap-independent initiation is poorly understood. We
      have previously reported the secondary structure within the yeast minimal URE2
      IRES element. In this study, we sought to investigate the mechanism of internal
      initiation in yeast by assessing the functional role of nucleotides within the
      minimal URE2 IRES element, and delineating the cis-sequences that modulate levels
      of internal initiation using a monocistronic reporter vector. Furthermore, we
      compared the eIF2A sensitivity of the URE2 IRES element with some of the invasive
      growth IRES elements using DeltaeIF2A yeast. We found that the stability of the
      stem-loop structure within the minimal URE2 IRES element is not a critical
      determinant of optimal IRES activity, and the downstream sequences that modulate
      URE2 IRES-mediated translation can be defined to discrete regions within the URE2
      coding region. Repression of internal initiation on the URE2 minimal IRES element
      by eIF2A is not dependent on the stability of the secondary structure within the
      URE2 IRES element. Our data also indicate that eIF2A-mediated repression is not
      specific to the URE2 IRES element, as both the GIC1 and PAB1 IRES elements are
      repressed by eIF2A. These data provide valuable insights into the mRNA
      requirements for internal initiation in yeast, and insights into the mechanism of
      eIF2A-mediated suppression.

PMID- 19861429
TI  - Sorafenib-induced hepatic encephalopathy.

PMID- 19861428
TI  - Absolute quantification of microRNAs by using a universal reference.
AB  - MicroRNAs (miRNAs) are a species of small RNAs approximately 21-23-nucleotides
      long that have been shown to play an important role in many different cellular,
      developmental, and physiological processes. Accordingly, numerous PCR-,
      sequencing-, or hybridization-based methods have been established to identify and
      quantify miRNAs. Their short length results in a high dynamic range of melting
      temperatures and therefore impedes a proper selection of detection probes or
      optimized PCR primers. While miRNA microarrays allow for massive parallel and
      accurate relative measurement of all known miRNAs, they have so far been less
      useful as an assay for absolute quantification. Here, we present a microarray
      based approach for global and absolute quantification of miRNAs. The method
      relies on the parallel hybridization of the sample of interest labeled with Cy5
      and a universal reference of 954 synthetic miRNAs in equimolar concentrations
      that are labeled with Cy3 on a microarray slide containing probes for all human,
      mouse, rat, and viral miRNAs (miRBase 12.0). Each single miRNA is quantified with
      respect to the universal reference canceling biases related to sequence,
      labeling, or hybridization. We demonstrate the accuracy of the method by various
      spike-in experiments. Furthermore, we quantified miRNA copy numbers in liver
      samples and CD34(+)/CD133(-) hematopoietic progenitor cells.

PMID- 19861430
TI  - Successful use of topical voriconazole 1% alone as first-line antifungal therapy
      against Candida albicans keratitis.
AB  - OBJECTIVE: To report the successful use of topical voriconazole 1% given alone as
      primary therapy against a case of Candida albicans keratitis. CASE SUMMARY: A 48
      year-old previously well man presented to the emergency department with pain and
      foreign body sensation in the left eye following exposure to dust while driving a
      forklift. He wore weekly disposable soft contact lenses. Anterior stromal scar
      and dense infiltrate were detected in the left eye. The anterior chamber remained
      deep, with flare and copious white cells. Intraocular pressure was 12 mm Hg and
      visual acuity was 20/200. The epithelial defect persisted, with progressive
      thinning despite topical fluorometholone and ofloxacin 0.3% therapy for 2 days.
      Microbiology testing revealed C. albicans as the affecting pathogen. Hourly
      administration of voriconazole 1% eye drops was initiated as antifungal therapy.
      The corneal infiltrate began to resolve and the epithelial defect decreased in
      size within 2 days. Visual acuity improved to 20/120. After 4 days of
      voriconazole use, the epithelial defect was completely healed and visual acuity
      was 20/30 in the affected eye. No fungi were isolated from a second eye scrape.
      DISCUSSION: Topical voriconazole as salvage monotherapy to manage fungal
      keratitis has been previously reported. It can be argued, however, that the
      primary therapy has facilitated the positive response to subsequent topical
      voriconazole. To date, there has been no solid evidence to suggest that topical
      voriconazole is effective when used as primary therapy. The current report
      provides evidence of topical voriconazole demonstrating clinical success when
      used as first-line therapy to treat C. albicans keratitis. The use of topical
      voriconazole can reduce the costs, toxicity, and drug interactions associated
      with common antifungal therapies. CONCLUSIONS: Topical voriconazole 1% eye drops
      administered alone demonstrated success as first-line therapy against the most
      common fungal keratitis, C. albicans keratitis.

PMID- 19861431
TI  - Identification and characterization of a novel ABCA3 mutation.
AB  - Mutations in the gene coding for ATP-binding cassette protein A3 (ABCA3) are
      recognized as a genetic cause of lung disease of varying severity.
      Characterization of a number of mutant ABCA3 proteins has demonstrated that the
      mutations generally affect intracellular localization or the ability of the
      protein to hydrolyze ATP. A novel heterozygous mutation that results in the
      substitution of cysteine for arginine at amino acid 295 in ABCA3 was identified
      in a premature infant with chronic respiratory insufficiency and abnormal
      lamellar bodies. Sequencing of DNA performed in study participants demonstrated
      that this was a mutation and not a common variant. Plasmid vectors containing
      ABCA3 with the identified novel mutation tagged with green fluorescent protein on
      the carboxy terminus were generated. The effect of the mutation on protein
      function was characterized by examining the glycosylation state of the mutant
      protein in transiently transfected HEK293 cells and by examining ATP hydrolysis
      activity of the mutant protein with a vanadate-induced nucleotide trapping assay
      in stably transfected HEK293 cells. The ABCA3 protein containing the R295C
      mutation undergoes normal glycosylation and intracellular localization but has
      dramatically reduced ATP hydrolysis activity (12% of wild type). The
      identification of one copy of this novel mutation in a premature infant with
      chronic respiratory insufficiency suggests that ABCA3 haploinsufficiency together
      with lung prematurity may result in more severe, or more prolonged, respiratory
      failure.

PMID- 19861432
TI  - Alterations in oxidative gene expression in equine skeletal muscle following
      exercise and training.
AB  - Intense selection for elite racing performance in the Thoroughbred horse (Equus
      caballus) has resulted in a number of adaptive physiological phenotypes relevant
      to exercise; however, the underlying molecular mechanisms responsible for these
      characteristics are not well understood. Adaptive changes in mRNA expression in
      equine skeletal muscle were investigated by real-time qRT-PCR for a panel of
      candidate exercise-response genes following a standardized incremental-step
      treadmill exercise test in eight untrained Thoroughbred horses. Biopsy samples
      were obtained from the gluteus medius before, immediately after, and 4 h after
      exercise. Significant (P < 0.05) differences in gene expression were detected for
      six genes (CKM, COX4I1, COX4I2, PDK4, PPARGC1A, and SLC2A4) 4 h after exercise.
      Investigation of relationships between mRNA and velocity at maximum heart rate
      (VHR(max)) and peak postexercise plasma lactate concentration ([La]T(1)) revealed
      significant (P < 0.05) associations with postexercise COX4I1 and PPARCG1A
      expression and between [La]T(1) and basal COX4I1 expression. Gene expression
      changes were investigated in a second cohort of horses after a 10 mo period of
      training. In resting samples, COX4I1 gene expression had significantly increased
      following training, and, after exercise, significant differences were identified
      for COX4I2, PDK4, and PPARGC1A. Significant relationships with VHR(max) and
      [La]T(1) were detected for PPARGC1A and COX4I1. These data highlight the roles of
      genes responsible for the regulation of oxygen-dependent metabolism, glucose
      metabolism, and fatty acid utilization in equine skeletal muscle adaptation to
      exercise.

PMID- 19861433
TI  - The neuropharmacokinetics of temozolomide in patients with resectable brain
      tumors: potential implications for the current approach to chemoradiation.
AB  - PURPOSE: Intracerebral microdialysis (ICMD) is an accepted method for monitoring
      changes in neurochemistry from acute brain injury. The goal of this pilot study
      was to determine the feasibility of using ICMD to examine the
      neuropharmacokinetics of temozolomide in brain interstitium following oral
      administration. EXPERIMENTAL DESIGN: Patients with primary or metastatic brain
      tumors had a microdialysis catheter placed in peritumoral brain tissue at the
      time of surgical debulking. Computerized tomography scan confirmed the catheter
      location. Patients received a single oral dose of temozolomide (150 mg/m2) on the
      first postoperative day, serial plasma and ICMD samples were collected over 24
      hours, and temozolomide concentrations were determined by tandem mass
      spectrometry. RESULTS: Nine patients were enrolled. Dialysate and plasma samples
      were successfully collected from seven of the nine patients. The mean
      temozolomide areas under the concentration-time curve (AUC) in plasma and brain
      interstitium were 17.1 and 2.7 microg/mL x hour, with an average brain
      interstitium/plasma AUC ratio of 17.8%. The mean peak temozolomide concentration
      in the brain was 0.6 +/- 0.3 microg/mL, and the mean time to reach peak level in
      brain was 2.0 +/- 0.8 hours. CONCLUSIONS: The use of ICMD to measure the
      neuropharmacokinetics of systemically administered chemotherapy is safe and
      feasible. Concentrations of temozolomide in brain interstitium obtained by ICMD
      are consistent with published data obtained in a preclinical ICMD model, as well
      as from clinical studies of cerebrospinal fluid. However, the delayed time
      required to achieve maximum temozolomide concentrations in brain suggests that
      current chemoradiation regimens may be improved by administering temozolomide 2
      to 3 hours before radiation.

PMID- 19861434
TI  - NKG2D ligand expression in human colorectal cancer reveals associations with
      prognosis and evidence for immunoediting.
AB  - PURPOSE: NKG2D (natural killer group 2, member D) binds to cellular ligands of
      the MIC and ULBP/RAET family. These ligands have restricted expression in normal
      tissue, but are frequently expressed on primary tumors. The role of NKG2D ligands
      is thought to be important in carcinogenesis but its prognostic effect has not
      been investigated in such a large cohort. EXPERIMENTAL DESIGN: In our study, 462
      primary colorectal tumors were screened for the expression of all MIC/ULBP/RAET
      proteins and NK cell infiltration. Tumor microarray technology was used for the
      purpose of this investigation. RESULTS: NKG2D ligands were expressed by the
      majority of colorectal tumors; however, the level of expression varied
      considerably. High expression of MIC (68 versus 56 months) or RAET1G (74 versus
      62 months) showed improved patient survival. Tumors expressing high levels of MIC
      and RAET1G showed improved survival of 77 months over tumors that expressed high
      levels of one ligand or low levels of both. High-level expression of all ligands
      was frequent in tumor-node-metastasis stage I tumors, but became progressively
      less frequent in stages II, III, and IV tumors. Expression of MIC was correlated
      with NK cellular infiltration. CONCLUSION: The observations presented are
      consistent with an immunoediting mechanism that selects tumor cells that have
      lost or reduced their expression of NKG2D ligands. The combination of MIC and
      tumor-node-metastasis stage was found to be the strongest predictor of survival,
      splitting patients into eight groups and suggesting prognostic value in clinical
      assessment. Of particular interest were stage I patients with low expression of
      MIC who had a similar survival to stage III patients, and may be candidates for
      adjuvant therapy.

PMID- 19861435
TI  - Comprehensive genomic analysis reveals clinically relevant molecular distinctions
      between thymic carcinomas and thymomas.
AB  - PURPOSE: Thymomas and thymic carcinomas are rare intrathoracic malignancies that
      can be invasive and refractory to conventional treatment. Because these tumors
      both originate from the thymus, they are often grouped together clinically.
      However, whether the underlying biology of these tumors warrants such clustering
      is unclear, and the optimum treatment of either entity is unknown. EXPERIMENTAL
      DESIGN: All thymic tumors were profiled for mutations in genes encoding
      components of the EGFR and KIT signaling pathways, assessed for EGFR and KIT
      expression by immunohistochemistry, and analyzed by array-based comparative
      genomic hybridization. Previously untreated tumors were subjected to global gene
      expression arrays. RESULTS: We analyzed 45 thymic tumors [thymoma, n = 38 (type
      A, n = 8; type B2, n = 22; type B3, n = 8); thymic carcinoma, n = 7]. One thymoma
      and one thymic carcinoma harbored KRAS mutations (G12A and G12V, respectively),
      and one thymoma had a G13V HRAS mutation. Three tumors displayed strong KIT
      staining. Two thymic carcinomas harbored somatic KIT mutations (V560del and
      H697Y). In cell viability assays, the V560del mutant was associated with similar
      sensitivities to imatinib and sunitinib, whereas the H697Y mutant displayed
      greater sensitivity to sunitinib. Genomic profiling revealed distinct differences
      between type A to B2 thymomas versus type B3 and thymic carcinomas. Moreover,
      array-based comparative genomic hybridization could readily distinguish squamous
      cell carcinomas of the thymus versus the lung, which can often present a
      diagnostic challenge. CONCLUSIONS: Comprehensive genomic analysis suggests that
      thymic carcinomas are molecularly distinct from thymomas. These data have
      clinical, pathologic, and therapeutic implications for the treatment of thymic
      malignancies.

PMID- 19861436
TI  - Reciprocal regulation of c-Src and STAT3 in non-small cell lung cancer.
AB  - PURPOSE: Signal transducer and activator of transcription-3 (STAT3) is downstream
      of growth factor and cytokine receptors, and regulates key oncogenic pathways in
      non-small cell lung cancer (NSCLC). Activation of STAT3 by cellular Src (c-Src)
      promotes tumor progression. We hypothesized that c-Src inhibition could activate
      STAT3 by inducing a homeostatic feedback loop, contributing to c-Src inhibitor
      resistance. EXPERIMENTAL DESIGN: The effects of c-Src inhibition on total and
      phosphorylated STAT3 were measured in NSCLC cell lines and in murine xenograft
      models by Western blotting. c-Src and STAT3 activity as indicated by
      phosphorylation was determined in 46 human tumors and paired normal lung by
      reverse phase protein array. Modulation of dasatinib (c-Src inhibitor)
      cytotoxicity by STAT3 knockdown was measured by MTT, cell cycle, and apoptosis
      assays. RESULTS: Depletion of c-Src by small interfering RNA or sustained
      inhibition by dasatinib increased pSTAT3, which could be blocked by inhibition of
      JAK. Similarly, in vivo pSTAT3 levels initially decreased but were strongly
      induced after sustained dasatinib treatment. In human tumors, phosphorylation of
      the autoinhibitory site of c-Src (Y527) correlated with STAT3 phosphorylation (r
      = 0.64; P = 2.5 x 10(-6)). STAT3 knockdown enhanced the cytotoxicity of
      dasatinib. CONCLUSIONS: c-Src inhibition leads to JAK-dependent STAT3 activation
      in vitro and in vivo. STAT3 knockdown enhances the cytotoxicity of dasatinib,
      suggesting a compensatory pathway that allows NSCLC survival. Data from human
      tumors showed a reciprocal regulation of c-Src and STAT3 activation, suggesting
      that this compensatory pathway functions in human NSCLC. These results provide a
      rationale for combining c-Src and STAT3 inhibition to improve clinical responses.

PMID- 19861437
TI  - DNA variants in region for noncoding interfering transcript of dihydrofolate
      reductase gene and outcome in childhood acute lymphoblastic leukemia.
AB  - PURPOSE: Dihydrofolate reductase (DHFR) is the major target of methotrexate, a
      key component in childhood acute lymphoblastic leukemia (ALL) treatment. We
      recently reported an association of DHFR promoter polymorphisms with ALL outcome.
      Lower event-free survival correlated with haplotype *1, defined by A(-317) and C(
      1610) alleles. Haplotype *1 was also associated higher DHFR expression.
      EXPERIMENTAL DESIGN: Here, we analyzed adjacent 400-bp region participating in
      DHFR regulation as both a major promoter and a noncoding minor transcript.
      RESULTS: Six polymorphisms were identified, of which five were single nucleotide
      polymorphisms and one was length polymorphism composed of variable number of 9-bp
      elements and 9-bp insertion/deletion. Haplotype analysis including all promoter
      polymorphisms revealed diversification of haplotype *1 into five subtypes (*1a
      *1e). DNA variations of major promoter/noncoding transcript region and haplotype
      *1 subtypes were subsequently analyzed for the association with ALL outcome.
      Lower event-free survival was associated with an A allele of G(308)A polymorphism
      (P = 0.02) and with *1b haplotype (P = 0.01). This association was particularly
      striking in high-risk patients (P = 0.001) and was subsequently confirmed in
      independent patient cohort (P = 0.02). Haplotype *1b was the only haplotype *1
      subtype associated with higher mRNA levels. CONCLUSIONS: The study provides a new
      insight into DHFR regulatory variations predisposing to an event in ALL patients.

PMID- 19861438
TI  - JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor,
      shows broad-spectrum preclinical antitumoral activity.
AB  - PURPOSE: Histone deacetylase (HDAC) inhibitors have shown promising clinical
      activity in the treatment of hematologic malignancies, but their activity in
      solid tumor indications has been limited. Most HDAC inhibitors in clinical
      development only transiently induce histone acetylation in tumor tissue. Here, we
      sought to identify a "second-generation" class I HDAC inhibitor with prolonged
      pharmacodynamic response in vivo, to assess whether this results in superior
      antitumoral efficacy. EXPERIMENTAL DESIGN: To identify novel HDAC inhibitors with
      superior pharmacodynamic properties, we developed a preclinical in vivo tumor
      model, in which tumor cells have been engineered to express fluorescent protein
      dependent on HDAC1 inhibition, thereby allowing noninvasive real-time evaluation
      of the tumor response to HDAC inhibitors. RESULTS: In vivo pharmacodynamic
      analysis of 140 potent pyrimidyl-hydroxamic acid analogues resulted in the
      identification of JNJ-26481585. Once daily oral administration of JNJ-26481585
      induced continuous histone H3 acetylation. The prolonged pharmacodynamic response
      translated into complete tumor growth inhibition in Ras mutant HCT116 colon
      carcinoma xenografts, whereas 5-fluorouracil was less active. JNJ-26481585 also
      fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again
      5-fluorouracil/Leucovorin showed modest activity. Further characterization
      revealed that JNJ-26481585 is a pan-HDAC inhibitor with marked potency toward
      HDAC1 (IC(50), 0.16 nmol/L). CONCLUSIONS: The potent antitumor activity as a
      single agent in preclinical models combined with its favorable pharmacodynamic
      profile makes JNJ-26481585 a promising "second-generation" HDAC inhibitor. The
      compound is currently in clinical studies, to evaluate its potential
      applicability in a broad spectrum of both solid and hematologic malignancies.

PMID- 19861439
TI  - Intratumoral expression of mature human neutrophil peptide-1 mediates antitumor
      immunity in mice.
AB  - PURPOSE: Human neutrophil peptides (HNP1-3), small molecular antimicrobial
      peptides, are expressed within tumors and associated with tumor necrosis and
      inhibition of angiogenesis. Recent investigations have suggested that HNP1-3 are
      likely to be involved in the host immune responses to tumors. EXPERIMENTAL
      DESIGN: We used recombinant pSec-HNP1, which expresses a secretable form of HNP1,
      to obtain expression of HNP1 in the tumor milieu in immunocompetent mice to
      explore the possible roles of HNP1 in tumor immunity. The antitumor effects were
      investigated in established CT26 colon cancer and 4T1 breast cancer models.
      RESULTS: HNP1-mediated chemotactic and activating effects on immature dendritic
      cells were detected both in vitro and in vivo. Intratumoral expression of HNP1
      resulted in not only significant tumor growth inhibition but also increased CTL
      infiltration within tumors. Adoptive transfer of splenocytes and a (51)Cr release
      assay revealed specific cellular immune responses. Furthermore, increased
      antibodies were also found in sera from pSec-HNP1-treated mice supporting
      specific humoral immune responses. Increased apoptosis and decreased angiogenesis
      were also shown in treated tumors. CONCLUSIONS: These findings indicate that HNP1
      can exert multiple antitumor effects through different mechanisms; more
      importantly, HNP1 mediates host immune responses to tumors in situ through the
      recruitment and subsequent activation of immature dendritic cells and thus shows
      promising potential in cancer therapy.

PMID- 19861440
TI  - Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1
      deficient colorectal cancer HCT116 cells.
AB  - PURPOSE: MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining
      genomic stability by participating in the repair of endogenous and exogenous
      mispairs in the daughter strands during S phase. Exogenous mispairs can result
      following treatment with several classes of chemotherapeutic drugs, as well as
      with ionizing radiation. In this study, we investigated the role of the MLH1
      protein in determining the cellular and molecular responses to prolonged low-dose
      rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer
      brachytherapy. EXPERIMENTAL DESIGN: An isogenic pair of MMR(+) (MLH1(+)) and MMR(
      ) (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR
      (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were
      examined. Cell cycle distribution was analyzed with flow cytometry. Changes in
      selected DNA damage repair proteins, DNA damage response proteins, and cell death
      marker proteins were examined with Western blotting. RESULTS: MLH1(+) HCT116
      cells showed greater radiosensitivity with enhanced expression of apoptotic and
      autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell
      cycle alterations (increased late-S population and a G(2)/M arrest) following LDR
      IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in
      MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was
      temporally correlated with a progressive decrease in Rad51 protein (involved in
      homologous recombination) levels. CONCLUSIONS: MLH1 status significantly affects
      cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to
      prolonged LDR-IR through inhibition of homologous recombination (through
      inhibition of Rad51).

PMID- 19861441
TI  - Tumor-derived tissue factor-bearing microparticles are associated with venous
      thromboembolic events in malignancy.
AB  - PURPOSE: Despite the strong association between malignant disease and
      thromboembolic disorders, the molecular and cellular basis of this relationship
      remains uncertain. We evaluated the hypothesis that tumor-derived tissue factor
      bearing microparticles in plasma contribute to cancer-associated thrombosis.
      EXPERIMENTAL DESIGN: We developed impedance-based flow cytometry to detect,
      quantitate, and size microparticles in platelet-poor plasma. We evaluated the
      number of tissue factor-bearing microparticles in a cohort of cancer patients of
      different histologies (N = 96) and conducted a case-control study of 30 cancer
      patients diagnosed with an acute venous thromboembolic event (VTE) compared with
      60 cancer patients of similar age, stage, sex, and diagnosis without known VTE,
      as well as 22 patients with an idiopathic VTE. RESULTS: Tissue factor-bearing
      microparticles were detected in patients with advanced malignancy, including two
      thirds of patients with pancreatic carcinoma. Elevated levels of tissue factor
      bearing microparticles were associated VTE in cancer patients (adjusted odds
      ratio, 3.72; 95% confidence interval, 1.18-11.76; P = 0.01). In cancer patients
      without VTE, a retrospective analysis revealed a 1-year cumulative incidence of
      VTE of 34.8% in patients with tissue factor-bearing microparticles versus 0% in
      those without detectable tissue factor-bearing microparticles (Gray test P =
      0.002).The median number of tissue factor-bearing microparticles in the cancer
      VTE cohort (7.1 x 10(4) microparticles/microL) was significantly greater than
      both the idiopathic VTE and cancer-no VTE groups (P = 0.002 and P = 0.03,
      respectively). Pancreatectomy in three patients eliminated or nearly eliminated
      these microparticles which coexpressed the epithelial tumor antigen, MUC-1.
      CONCLUSION: We conclude that tumor-derived tissue factor-bearing microparticles
      are associated with VTE in cancer patients and may be central to the pathogenesis
      of cancer-associated thrombosis.

PMID- 19861442
TI  - Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring
      KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance.
AB  - PURPOSE: Although tyrosine kinase inhibitors have improved survival in advanced
      gastrointestinal stromal tumor (GIST), complete response is rare and most
      patients eventually fail the first-line treatment with imatinib. Sunitinib malate
      is the only approved second-line therapy for patients with imatinib-resistant or
      imatinib-intolerant GIST. The clinical benefit of sunitinib is genotype-dependent
      in regards to both primary and secondary mutations, with GIST patients harboring
      the KIT(AY502-3ins) exon 9 mutation being the most sensitive. EXPERIMENTAL
      DESIGN: As sunitinib resistance is now emerging, our goal was to investigate
      mechanisms of progression and to test the efficacy of novel tyrosine kinase
      inhibitor on these resistant mutants in vitro. N-ethyl-N-nitrosourea mutagenesis
      of Ba/F3 cells expressing the KIT(AY502-3ins) mutant was used to investigate
      novel patterns of resistant mutations evolving in the presence of sunitinib.
      RESULTS: Tumors from patients who developed sunitinib resistance after at least 1
      year of radiographic response were analyzed, showing similar findings of a
      primary KIT(AY502-3ins) mutation and a secondary mutation in the KIT activation
      loop. Ba/F3 cells expressing these sunitinib-resistant double mutants showed
      sensitivity to both dasatinib and nilotinib. CONCLUSIONS: Sunitinib resistance in
      GIST shares similar pathogenetic mechanisms identified in imatinib failure, with
      acquisition of secondary mutations in the activation domain after an extended
      initial response to the drug. Moreover, in vitro mutagenesis with or without N
      ethyl-N-nitrosourea of Ba/F3 cells expressing KIT(AY502-3ins) showed acquisition
      of secondary mutations restricted to the second kinase domain of KIT. In
      contrast, in vitro resistance to imatinib produces a broader spectrum of
      secondary mutations including mutations in both KIT kinase domains.

PMID- 19861444
TI  - Human papillomavirus in head and neck cancer: its role in pathogenesis and
      clinical implications.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      with an annual incidence of approximately 400,000 worldwide. Although the
      principal risk factors for head and neck cancer remain tobacco and alcohol use,
      human papillomavirus (HPV) has recently been found to be etiologically associated
      with 20 to 25% of HNSCC, mostly in the oropharynx. HPV causes human cancers by
      expressing two viral oncoproteins, E6 and E7. These oncoproteins degrade and
      destabilize two major tumor suppressor proteins, p53 and pRb, through
      ubiquitination. Additional studies have shown that E6 and E7 can directly bind to
      multiple host proteins other than p53 and pRb (e.g., Bak and p21(Cip1)), further
      contributing to genetic instability. However, expression of E6 and E7 alone is
      not sufficient for cellular transformation, and the additional genetic
      alterations necessary for malignant progression in the setting of virus-induced
      genomic instability are unknown. In addition to the etiological differences, HPV
      positive cancers are clinically distinct when compared with HPV-negative cancers
      with regard to treatment response and survival outcome, with tumor HPV-positivity
      being a favorable prognostic biomarker. Further understanding of carcinogenesis
      and clinical behavior of HPV-positive cancers will improve disease prevention,
      patient care, and surveillance strategies for HNSCC patients.

PMID- 19861443
TI  - A genomic approach to improve prognosis and predict therapeutic response in
      chronic lymphocytic leukemia.
AB  - PURPOSE: Chronic lymphocytic leukemia (CLL) is a B-cell malignancy characterized
      by a variable clinical course. Several parameters have prognostic capabilities
      but are associated with altered response to therapy in only a small subset of
      patients. EXPERIMENTAL DESIGN: We used gene expression profiling methods to
      generate predictors of therapy response and prognosis. Genomic signatures that
      reflect progressive disease and responses to chemotherapy or chemoimmunotherapy
      were created using cancer cell lines and patient leukemia cell samples. We
      validated and applied these three signatures to independent clinical data from
      four cohorts, representing a total of 301 CLL patients. RESULTS: A genomic
      signature of prognosis created from patient leukemic cell gene expression data
      coupled with clinical parameters significantly differentiated patients with
      stable disease from those with progressive disease in the training data set. The
      progression signature was validated in two independent data sets, showing a
      capacity to accurately identify patients at risk for progressive disease. In
      addition, genomic signatures that predict response to chlorambucil or
      pentostatin, cyclophosphamide, and rituximab were generated and could accurately
      distinguish responding and nonresponding CLL patients. CONCLUSIONS: Thus,
      microarray analysis of CLL lymphocytes can be used to refine prognosis and
      predict response to different therapies. These results have implications for
      standard and investigational therapeutics in CLL patients.

PMID- 19861445
TI  - Quantification of circulating vascular endothelial growth factor receptor-3
      positive lymphatic/vascular endothelial progenitor cells.

PMID- 19861446
TI  - Enhancing cancer vaccine efficacy via modulation of the tumor microenvironment.
AB  - The development of therapeutic cancer vaccines is impacted by immunosuppressive
      elements in the tumor microenvironment. Most immunogenic cancer proteins are
      "self," therefore, peripheral tolerance contributes substantially to tumor immune
      escape. Transforming growth factor beta (TGFbeta) actively modulates both
      inflammation and tolerance induction. Combining vaccination with agents that
      disarm TGFbeta will enhance vaccine efficacy.

PMID- 19861447
TI  - Altered tissue 3'-deoxy-3'-[18F]fluorothymidine pharmacokinetics in human breast
      cancer following capecitabine treatment detected by positron emission tomography.
AB  - PURPOSE: We showed in preclinical models that thymidylate synthase (TS)
      inhibition leads to redistribution of the nucleoside transporter, ENT1, to the
      cell membrane and hence increases tissue uptake of [(18)F]fluorothymidine (FLT).
      In this study, we assessed for the first time the altered pharmacokinetics of FLT
      in patients following administration of capecitabine, a drug whose mode of action
      has been reported to include TS inhibition. EXPERIMENTAL DESIGN: We analyzed 10
      lesions from six patients with breast cancer by positron emission tomography
      before and after treatment with capecitabine. Although drug treatment did not
      alter tumor delivery pharmacokinetic variables (K1 and permeability product
      surface area) or blood flow, tumor FLT retention variables increased with drug
      treatment in all but one patient. RESULTS: The baseline average standardized
      uptake value at 60 minutes, rate constant for the net irreversible transfer of
      radiotracer from plasma to tumor (Ki), and unit impulse response function at 60
      minutes were 11.11 x 10(-5) m(2)/mL, 4.38 x 10(-2) mL plasma/min/mL tissue, and
      4.93 x 10(-2)/min, respectively. One hour after capecitabine administration, the
      standardized uptake value was 13.55 x 10(-5) m(2)/mL (P = 0.004), Ki 7.40 x 10(
      2) mL plasma/min/mL tissue (P = 0.004), and impulse response function was 7.40 x
      10(-2)/min (P = 0.002). FLT pharmacokinetics did not change in normal tissues,
      suggesting that the effect was largely restricted to tumors (P = 0.55).
      CONCLUSIONS: We have identified FLT positron emission tomography retention
      parameters that could be used in future early clinical studies to measure the
      pharmacodynamics of TS inhibitors, as well as for identifying patients who are
      unlikely to benefit from TS inhibition.

PMID- 19861448
TI  - Rituximab-mediated cell signaling and chemo/immuno-sensitization of drug
      resistant B-NHL is independent of its Fc functions.
AB  - PURPOSE: Rituximab [chimeric anti-CD20 monoclonal antibody], alone or combined
      with chemotherapy, is used in the treatment of non-Hodgkin's lymphoma (NHL).
      Rituximab binds to CD20 and inhibits intracellular survival/growth pathways
      leading to chemo/immunosensitization of tumor cells in vitro. The contribution of
      rituximab Fc-FcR interaction in signaling is not known. This study examined the
      role of Fc-FcR interactions in rituximab-induced signaling using rituximab
      (Fab')(2) fragments as well as rituximab devoid of the CH2 Fc-binding domain
      (CH2(-)). EXPERIMENTAL DESIGN: Rituximab (CH2(-)) and rituximab (Fab')(2) were
      tested for their activity on B-NHL cell lines. Cell signaling and sensitization
      to chemotherapy and immunotherapy were examined. The in vitro studies were
      validated in mice bearing tumor xenografts. RESULTS: Although the modified
      antibodies were defective in antibody-dependent cellular cytotoxicity and
      complement-dependent cytotoxicity functions, they retained all other biological
      activities such as inhibition of cell proliferation, induction of cell
      aggregation, and apoptosis induction. In addition, similar to rituximab, the
      modified antibodies inhibited the activity of cell survival/growth pathways and
      their associated transcription factors (e.g., NF-kappaB, YY1, SP-1), and signal
      transducers and activators of transcription 3 (STAT-3), and downregulated the
      expression of antiapoptotic gene products, such as Bcl-2/Bcl(xl), which regulate
      drug resistance. The modified antibodies, similar to rituximab, sensitized
      resistant B-NHL cells to both CDDP and Fas ligand-induced apoptosis. Furthermore,
      treatment of nude mice bearing Raji tumor cell xenografts with the combination of
      rituximab (Fab')(2) or rituximab and CDDP resulted in similar and significant
      inhibition of tumor growth. CONCLUSION: These findings reveal that rituximab
      mediated inhibition of intracellular signaling pathways and leading to
      chemo/immuno-sensitization of resistant B-NHL is Fc independent.

PMID- 19861449
TI  - Serum molecular signatures of weight change during early breast cancer
      chemotherapy.
AB  - PURPOSE: Weight gain in women receiving chemotherapy for breast cancer is
      associated with a higher risk of recurrence but its mechanisms are poorly
      understood. EXPERIMENTAL DESIGN: To investigate this, we assessed the metabolic,
      cytokine, and appetite-related peptide alterations during adjuvant chemotherapy
      for early breast cancer in postmenopausal women, and correlated these with body
      mass measurements. Specifically, we performed global metabolic profiling using
      (1)H-nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin
      immunoreactivity, RIAs for GLP-1 and peptide YY, and electrochemiluminescent
      cytokine analyses (tumor necrosis factor-alpha and interleukin-6) on sequential
      samples. RESULTS: In those who gained >1.5 kg, several metabolite levels were
      positively associated with weight gain, specifically lactate, which was 63.5%
      greater in patients with increased body weight during chemotherapy compared with
      those with no weight gain (P < 0.01; the prespecified primary end point). A
      strong correlation (r = 0.7, P < 0.001) was detected between the rate of weight
      change and serum lactate levels, and on average, lactate levels exhibited the
      greatest metabolic response to chemotherapy, increasing by up to 75%. Normalized
      levels of peptide YY were also observed to be elevated in patients not gaining
      weight posttreatment (+30% compared with -7% for the weight gain group; P < 10(
      4)). Baseline lactate, alanine, and body fat were all prognostic for weight gain
      (area under the receiver operator characteristic curves, >0.77; P < 0.05). No
      associations were observed between any other parameter and weight gain, including
      cytokine levels. CONCLUSIONS: Metabonomics identifies excess energy expenditure
      pathways perturbed during chemotherapy for breast cancer, and establishes a
      significant association between serum lactate, body fat, and substantive weight
      gain during chemotherapy.

PMID- 19861450
TI  - Gene expression profiling for discovery of novel markers of minimal disease.

PMID- 19861451
TI  - Synergistic enhancement of CD8+ T cell-mediated tumor vaccine efficacy by an anti
      transforming growth factor-beta monoclonal antibody.
AB  - PURPOSE: Transforming growth factor-beta (TGF-beta) is an immunosuppressive
      cytokine, having direct suppressive activity against conventional CD4(+) and
      CD8(+)T cells and natural killer cells, thereby inhibiting tumor
      immunosurveillance. Here, we investigated possible synergy between anti-TGF-beta
      (1D11) and a peptide vaccine on induction of antitumor immunity, and the
      mechanisms accounting for synergistic efficacy. EXPERIMENTAL DESIGN: The effect
      of combination treatment with a peptide vaccine and anti-TGF-beta was examined in
      a subcutaneous TC1 tumor model, as well as the mechanisms of protection induced
      by this treatment. RESULTS: Anti-TGF-beta significantly and synergistically
      improved vaccine efficacy as measured by reduction in primary tumor growth,
      although anti-TGF-beta alone had no impact. The number of tumor antigen-specific
      CTL with high functional avidity as measured by IFN-gamma production and lytic
      activity was significantly increased in vaccinated mice by TGF-beta
      neutralization. Although TGF-beta is known to play a critical role in
      CD4(+)Foxp3(+) Treg cells, Treg depletion/suppression by an anti-CD25 monoclonal
      antibody (PC61) before tumor challenge did not enhance vaccine efficacy, and
      adding anti-TGF-beta did not affect Treg numbers in lymph nodes or tumors or
      their function. Also, TGF-beta neutralization had no effect on interleukin-17
      producing T cells, which are induced by TGF-beta and interleukin-6. Absence of
      type II NKT cells, which induce myeloid cells to produce TGF-beta, was not
      sufficient to eliminate all sources of suppressive TGF-beta. Finally, the
      synergistic protection induced by anti-TGF-beta vaccine augmentation was mediated
      by CD8(+) T cells since anti-CD8 treatment completely abrogated the effect.
      CONCLUSIONS: These results suggest that TGF-beta blockade may be useful for
      enhancing cancer vaccine efficacy.

PMID- 19861452
TI  - Metabolic approaches to treatment of melanoma.
AB  - PURPOSE: Lactate dehydrogenase (LDH) levels in blood of patients with melanoma
      have proven to be an accurate predictor of prognosis and response to some
      treatments. Exclusion of patients with high LDH levels from many trials of new
      treatments has created a need for treatments aimed at patients with high LDH
      levels. This article reviews the metabolic basis for the association of LDH with
      prognosis and the treatment initiatives that may be successful in this patient
      group. EXPERIMENTAL DESIGN: Review of current literature on the topic. RESULTS: A
      number of new treatment initiatives based on manipulation of metabolic pathways
      in melanoma cells are now available and await evaluation in well-designed
      clinical trials. CONCLUSIONS: Different cancers may require different metabolic
      approaches for effective treatment. In view of the high rate of glycolysis in
      most melanoma cells, approaches based on inhibition of acid excretion from the
      cells seem particularly attractive.

PMID- 19861455
TI  - Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.
AB  - PURPOSE: The targeting protein for Xklp2 (TPX2) has recently gained attention as
      a putative oncogene possibly amplified in several human malignancies, including
      pancreatic adenocarcinoma. In this work, we sought to evaluate the copy number
      and expression of TPX2 in pancreatic cancer cell lines and tumor tissues and to
      further explore the potential of TPX2 as a therapeutic target. EXPERIMENTAL
      DESIGN: The DNA copy number and expression of the TPX2 gene were surveyed in
      pancreatic cancer cell lines and tumor tissues and compared with those of
      immortalized normal pancreatic ductal cells and normal pancreatic tissues. The
      cellular effects of TPX2 knockdown using small interfering RNA oligonucleotides
      in pancreatic cancer cells, such as growth in tissue culture, in soft agar, and
      in nude mice; apoptosis; and sensitivity to paclitaxel, were also investigated
      using various assays. RESULTS: Low-copy-number TPX2 amplification was found in
      pancreatic cancer cell lines and low-passage pancreatic cancer tumor xenografts.
      TPX2 expression was upregulated in pancreatic cancer cell lines at both the mRNA
      and protein levels relative to the immortalized pancreatic ductal epithelial cell
      line HPDE6. Immunohistochemical staining of a tissue microarray showed that TPX2
      expression was higher in pancreatic tumors compared with their normal
      counterparts. Treatment with TPX2 targeting small interfering RNAs effectively
      reduced pancreatic cancer cell growth in tissue culture, induced apoptosis, and
      inhibited growth in soft agar and in nude mice. Knockdown of TPX2 also sensitized
      pancreatic cancer cells to paclitaxel treatment. CONCLUSIONS: Our results suggest
      that TPX2 might be an attractive target for pancreatic cancer therapy.

PMID- 19861456
TI  - The p53 family protein p73 provides new insights into cancer chemosensitivity and
      targeting.
AB  - The p53 tumor suppressor is part of a small family of related proteins that
      includes two other members, p73 and p63. Interest in the p53 family members,
      their functions and their complex interactions and regulation, has steadily grown
      over recent years and does not show signs of waning. p73 is a major determinant
      of chemosensitivity in humans, and mutant p53 proteins carrying specific
      polymorphisms can induce drug resistance by inhibiting TAp73. Cooperation between
      TA (transactivating, proapoptotic, antiproliferative) and Delta N (truncated,
      antiapoptotic, pro-proliferative) p73 isoforms and among the three family members
      guarantees equilibrium between proliferation, differentiation, and cell death,
      thus creating a harmony that is lost in several human cancers. In this article,
      we review our current knowledge of the role of p73 in cancer chemosensitivity and
      the real prospect of therapy targeting this molecule. We also draw attention to
      the crucial role of specific phosphorylation and acetylation events for p73
      induced apoptosis and drug chemosensitivity.

PMID- 19861457
TI  - In vitro and clinical studies of gene therapy with recombinant human adenovirus
      p53 injection for oral leukoplakia.
AB  - PURPOSE: Oral leukoplakia is a well-recognized precancerous lesion of squamous
      cell carcinoma. When accompanied with abnormal p53 expression, it suffered a
      higher risk of canceration. The present study was carried out to test whether the
      recombinant human adenovirus-p53 could introduce wild-type p53 gene to oral
      leukoplakia cells and induce cell cycle arrest and apoptosis. EXPERIMENTAL
      DESIGN: We select p53(-) oral dysplastic keratinocyte POE-9n, to observe the
      growth inhibition, cell cycle change, apoptosis-induced effects, and elaborate
      the corresponding molecular mechanism of recombinant adenovirus-p53 on POE-9n
      cells. Meanwhile, we evaluate the feasibility, safety, and biological activity of
      multipoints intraepithelial injections of recombinant adenovirus-p53 in 22
      patients with dysplastic oral leukoplakia. RESULTS: Exogenous p53 could be
      successfully transduced into POE-9n cells by recombinant adenovirus-p53. The
      optimal infecting titer in this study was multiplicity of infection (MOI) = 100.
      Recombinant adenovirus-p53 could strongly inhibit cell proliferation, induce
      apoptosis, and arrest cell cycle in stage G(1) in POE-9n cells by inducing
      p21(CIP/WAF) and downregulating bcl-2 expression. In the posttreatment patients,
      p53 protein and p21(CIP/WAF) protein expression were significantly enhanced, yet
      bcl-2 protein presented low expression. Sixteen patients showed clinical response
      to the treatment, and 14 patients showed obvious histopathologic improvement.
      CONCLUSION: Intraepithelial injections of recombinant human adenovirus-p53 were
      safe, feasible, and biologically active for patients with dysplastic oral
      leukoplakia.

PMID- 19861458
TI  - Quantifying antivascular effects of monoclonal antibodies to vascular endothelial
      growth factor: insights from imaging.
AB  - PURPOSE: Little is known concerning the onset, duration, and magnitude of direct
      therapeutic effects of anti-vascular endothelial growth factor (VEGF) therapies.
      Such knowledge would help guide the rational development of targeted therapeutics
      from bench to bedside and optimize use of imaging technologies that quantify
      tumor function in early-phase clinical trials. EXPERIMENTAL DESIGN: Preclinical
      studies were done using ex vivo microcomputed tomography and in vivo ultrasound
      imaging to characterize tumor vasculature in a human HM-7 colorectal xenograft
      model treated with the anti-VEGF antibody G6-31. Clinical evaluation was by
      quantitative magnetic resonance imaging in 10 patients with metastatic colorectal
      cancer treated with bevacizumab. RESULTS: Microcomputed tomography experiments
      showed reduction in perfused vessels within 24 to 48 h of G6-31 drug
      administration (P <or= 0.005). Ultrasound imaging confirmed reduced tumor blood
      volume within the same time frame (P = 0.048). Consistent with the preclinical
      results, reductions in enhancing fraction and fractional plasma volume were
      detected in patient colorectal cancer metastases within 48 h after a single dose
      of bevacizumab that persisted throughout one cycle of therapy. These effects were
      followed by resolution of edema (P = 0.0023) and tumor shrinkage in 9 of 26
      tumors at day 12. CONCLUSION: These data suggest that VEGF-specific inhibition
      induces rapid structural and functional effects with downstream significant
      antitumor activity within one cycle of therapy. This finding has important
      implications for the design of early-phase clinical trials that incorporate
      physiologic imaging. The study shows how animal data help interpret clinical
      imaging data, an important step toward the validation of image biomarkers of
      tumor structure and function.

PMID- 19861459
TI  - MYC-induced cancer cell energy metabolism and therapeutic opportunities.
AB  - Although cancers have altered glucose metabolism, termed the Warburg effect,
      which describes the increased uptake and conversion of glucose to lactate by
      cancer cells under adequate oxygen tension, changes in the metabolism of
      glutamine and fatty acid have also been documented. The MYC oncogene, which
      contributes to the genesis of many human cancers, encodes a transcription factor
      c-Myc, which links altered cellular metabolism to tumorigenesis. c-Myc regulates
      genes involved in the biogenesis of ribosomes and mitochondria, and regulation of
      glucose and glutamine metabolism. With E2F1, c-Myc induces genes involved in
      nucleotide metabolism and DNA replication, and microRNAs that homeostatically
      attenuate E2F1 expression. With the hypoxia inducible transcription factor HIF-1,
      ectopic c-Myc cooperatively induces a transcriptional program for hypoxic
      adaptation. Myc regulates gene expression either directly, such as glycolytic
      genes including lactate dehydrogenase A (LDHA), or indirectly, such as repression
      of microRNAs miR-23a/b to increase glutaminase (GLS) protein expression and
      glutamine metabolism. Ectopic MYC expression in cancers, therefore, could
      concurrently drive aerobic glycolysis and/or oxidative phosphorylation to provide
      sufficient energy and anabolic substrates for cell growth and proliferation in
      the context of the tumor microenvironment. Collectively, these studies indicate
      that Myc-mediated altered cancer cell energy metabolism could be translated for
      the development of new anticancer therapies.

PMID- 19861460
TI  - Genomic and expression profiling of glioblastoma stem cell-like spheroid cultures
      identifies novel tumor-relevant genes associated with survival.
AB  - PURPOSE: Glioblastoma spheroid cultures are enriched in tumor stem-like cells and
      therefore may be more representative of the respective primary tumors than
      conventional monolayer cultures. We exploited the glioma spheroid culture model
      to find novel tumor-relevant genes. EXPERIMENTAL DESIGN: We carried out array
      based comparative genomic hybridization of spheroid cultures derived from 20
      glioblastomas. Microarray-based gene expression analysis was applied to determine
      genes with differential expression compared with normal brain tissue and to
      nonneoplastic brain spheroids in glioma spheroid cultures. The protein expression
      levels of three candidates were determined by immunohistochemistry on tissue
      microarrays and correlated with clinical outcome. Functional analysis of PDPN was
      done. RESULTS: Genomic changes in spheroid cultures closely resembled those
      detected in primary tumors of the corresponding patients. In contrast, genomic
      changes in serum-grown monolayer cultures established from the same patients did
      not match well with the respective primary tumors. Microarray-based gene
      expression analysis of glioblastoma spheroid cultures identified a set of novel
      candidate genes being upregulated or downregulated relative to normal brain.
      Quantitative real-time PCR analyses of 8 selected candidate genes in 20 clinical
      glioblastoma samples validated the microarray findings. Immunohistochemistry on
      tissue microarrays revealed that expression of AJAP1, EMP3, and PDPN was
      significantly associated with overall survival of astrocytic glioma patients.
      Invasive capacity and RhoA activity were decreased in PDPN-silenced spheroids.
      CONCLUSION: We identified a set of novel candidate genes that likely play a role
      in glioblastoma pathogenesis and implicate AJAP1, EMP3, and PDPN as molecular
      markers associated with the clinical outcome of glioma patients.

PMID- 19861461
TI  - Prognostic significance of molecular markers and extent of resection in primary
      glioblastoma patients.
AB  - PURPOSE: Despite multimodal aggressive treatment glioblastoma patients still face
      a rather poor prognosis. Recent data indicate that certain molecular markers, in
      particular MGMT promoter hypermethylation, are associated with response to
      alkylating chemotherapy and longer survival. The clinical significance of other
      glioblastoma-associated molecular aberrations and their relationship to MGMT
      promoter hypermethylation is still poorly understood. EXPERIMENTAL DESIGN: We
      conducted a translational study involving 67 newly diagnosed glioblastoma
      patients treated at our institution from 1998 to 2004. All patients were treated
      by open resection, followed by radiotherapy and adjuvant temozolomide
      chemotherapy. The tumors were investigated for MGMT promoter methylation, mRNA
      and protein expression, as well as presence of MGMT sequence polymorphisms. In
      addition, we screened for genetic aberrations of the EGFR, TP53, CDK4, MDM2, and
      PDGFRA genes as well as allelic losses on chromosomal arms 1p, 10q, and 19q.
      RESULTS: Correlation of molecular findings with clinical data revealed
      significantly longer time to progression after onset of chemotherapy and longer
      overall survival of patients with MGMT-hypermethylated tumors. In contrast, MGMT
      protein expression, MGMT polymorphisms, and aberrations in any of the other genes
      and chromosomes were not significantly linked to patient outcome. Multivariate
      analysis identified MGMT promoter hypermethylation and near-complete tumor
      resection as the most important parameters associated with better prognosis.
      CONCLUSION: Our study provides novel insights into the significance of molecular
      and clinical markers in predicting the prognosis of glioblastoma patients, which
      may improve stratification of patients into distinct prognostic subgroups.

PMID- 19861463
TI  - Has quantitative multimodal imaging of treatment response arrived?
AB  - Although there have been dramatic increases in the range and quality of
      information available from noninvasive imaging methods, their application in
      clinical trials has been limited. One promising approach is to apply imaging
      techniques in preclinical studies designed to mimic a corresponding clinical
      trial in order to inform that trial.

PMID- 19861462
TI  - Nuclear translocation of the epidermal growth factor receptor family membrane
      tyrosine kinase receptors.
AB  - Integral membrane proteins contain a hydrophobic transmembrane domain and mainly
      locate in the plasma membrane lipid bilayer. The receptor tyrosine kinases (RTK)
      of the epidermal growth factor receptor (EGFR) superfamily, including ErbB-1,
      ErbB-2, ErbB-3, and ErbB-4, constitute an important group of such membrane
      proteins, which have a profound impact on cancer initiation, progression, and
      patient outcome. Although studies of their functions have conventionally focused
      on their membrane-associated forms, documented observations of the presence of
      these membrane receptors and their functioning partners in the nucleus have
      reshaped the intracellular geography and highlight the need to modify the central
      dogma. The ErbB proteins in the membrane can translocate to the nucleus through
      different mechanisms. Nuclear RTKs regulate a variety of cellular functions, such
      as cell proliferation, DNA damage repair, and signal transduction, both in normal
      tissues and in human cancer cell. In addition, they play important roles in
      determining cancer response to cancer therapy. Nuclear presence of these ErbB
      proteins is emerging as an important marker in human cancers. An integrated
      picture of the RTK-centered signaling transduction network extending from the
      membrane-cytoplasm boundary to the nuclear compartment is looming in the
      foreseeable horizon for clinical application.

PMID- 19861465
TI  - Targeted radionuclide therapy using a Wnt-targeted replicating adenovirus
      encoding the Na/I symporter.
AB  - PURPOSE: The Na/I symporter (hNIS) promotes concentration of iodine in cells. In
      cancer gene therapy, this transgene has potential as a reporter gene for
      molecular imaging of viral biodistribution and as a therapeutic protein promoting
      (131)I-mediated radiotherapy. Here, we combined the imaging and therapeutic
      potential of hNIS in an oncolytic adenoviruses targeting colorectal cancer cells.
      EXPERIMENTAL DESIGN: We generated an adenovirus (AdIP2) encoding hNIS and capable
      of selective replication in colorectal carcinoma cells. The selectivity of this
      virus was verified in vitro and in vivo. Its spread in tumors was monitored in
      vivo using single-photon emission computed tomography/CT imaging upon
      (99m)TcO(4)(-) injection and confirmed by immunohistochemistry. Metabolic
      radiotherapy was done through injection of therapeutic doses of (131)I(-).
      RESULTS: We showed in vitro and in vivo the selectivity of AdIP2 and that hNIS
      expression is restricted to the target cells. Imaging and immunohistochemical
      data showed that viral spread is limited and that the point of maximal hNIS
      expression is reached 48 hours after a single intratumoral injection.
      Administration of a single therapeutic dose of (131)I at this time point led to a
      dramatic reduction in tumor size not observed in hNIS-negative viruses.
      CONCLUSIONS: This report showed for the first time that the combination of the
      imaging and therapeutic potentials of hNIS can be applied to oncolytic
      adenoviruses in experimental models of cancer.

PMID- 19861464
TI  - Systemic inhibition of transforming growth factor-beta in glioma-bearing mice
      improves the therapeutic efficacy of glioma-associated antigen peptide vaccines.
AB  - PURPOSE: A variety of cancers, including malignant gliomas, overexpress
      transforming growth factor-beta (TGF-beta), which helps tumors evade effective
      immune surveillance through a variety of mechanisms, including inhibition of
      CD8(+) CTLs and enhancing the generation of regulatory T (T(reg)) cells. We
      hypothesized that inhibition of TGF-beta would improve the efficacy of vaccines
      targeting glioma-associated antigen (GAA)-derived CTL epitopes by reversal of
      immunosuppression. EXPERIMENTAL DESIGN: Mice bearing orthotopic GL261 gliomas
      were treated systemically with a TGF-beta-neutralizing monoclonal antibody, 1D11,
      with or without s.c. vaccinations of synthetic peptides for GAA-derived CTL
      epitopes, GARC-1 (77-85) and EphA2 (671-679), emulsified in incomplete Freund's
      adjuvant. RESULTS: Mice receiving the combination regimen exhibited significantly
      prolonged survival compared with mice receiving either 1D11 alone, GAA vaccines
      alone, or mock treatments alone. TGF-beta neutralization enhanced the systemic
      induction of antigen-specific CTLs in glioma-bearing mice. Flow cytometric
      analyses of brain-infiltrating lymphocytes revealed that 1D11 treatment
      suppressed phosphorylation of Smad2, increased GAA-reactive/IFN-gamma-producing
      CD8(+) T cells, and reduced CD4(+)/FoxP3(+) T(reg) cells in the glioma
      microenvironment. Neutralization of TGF-beta also upregulated plasma levels of
      interleukin-12, macrophage inflammatory protein-1 alpha, and IFN-inducible
      protein-10, suggesting a systemic promotion of type-1 cytokine/chemokine
      production. Furthermore, 1D11 treatment upregulated plasma interleukin-15 levels
      and promoted the persistence of GAA-reactive CD8(+) T cells in glioma-bearing
      mice. CONCLUSIONS: These data suggest that systemic inhibition of TGF-beta by
      1D11 can reverse the suppressive immunologic environment of orthotopic tumor
      bearing mice both systemically and locally, thereby enhancing the therapeutic
      efficacy of GAA vaccines.

PMID- 19861466
TI  - Introduction: Child health disparities and health literacy.

PMID- 19861467
TI  - Health disparities beginning in childhood: a life-course perspective.
AB  - In this article we argue for the utility of the life-course perspective as a tool
      for understanding and addressing health disparities across socioeconomic and
      racial or ethnic groups, particularly disparities that originate in childhood.
      Key concepts and terms used in life-course research are briefly defined; as
      resources, examples of existing literature and the outcomes covered are provided
      along with examples of longitudinal databases that have often been used for life
      course research. The life-course perspective focuses on understanding how early
      life experiences can shape health across an entire lifetime and potentially
      across generations; it systematically directs attention to the role of context,
      including social and physical context along with biological factors, over time.
      This approach is particularly relevant to understanding and addressing health
      disparities, because social and physical contextual factors underlie
      socioeconomic and racial/ethnic disparities in health. A major focus of life
      course epidemiology has been to understand how early-life experiences
      (particularly experiences related to economic adversity and the social
      disadvantages that often accompany it) shape adult health, particularly adult
      chronic disease and its risk factors and consequences. The strong life-course
      influences on adult health could provide a powerful rationale for policies at all
      levels--federal, state, and local--to give more priority to investment in
      improving the living conditions of children as a strategy for improving health
      and reducing health disparities across the entire life course.

PMID- 19861468
TI  - Social inequality and racial discrimination: risk factors for health disparities
      in children of color.
AB  - A child's sense of control over life and health outcomes as well as perceptions
      of the world as fair, equal, and just are significantly influenced by his or her
      social experiences and environment. Unfortunately, the social environment for
      many children of color includes personal and family experiences of racial
      discrimination that foster perceptions of powerlessness, inequality, and
      injustice. In turn, these perceptions may influence child health outcomes and
      disparities by affecting biological functioning (eg, cardiovascular and immune
      function) and the quality of the parent-child relationship and promoting
      psychological distress (eg, self-efficacy, depression, anger) that can be
      associated with risk-taking and unhealthy behaviors. In this article we review
      existing theoretical models and empirical studies of the impact of racial
      discrimination on the health and development of children of color in the United
      States. On the basis of this literature, a conceptual model of exposure to racial
      discrimination as a chronic stressor and a risk factor for poor health outcomes
      and child health disparities is presented.

PMID- 19861469
TI  - Health disparities and children in immigrant families: a research agenda.
AB  - Children in immigrant families now comprise 1 in 5 children in the United States.
      Eighty percent of them are US citizens, and 53% live in mixed-citizenship
      families. Their families are among the poorest, least educated, least insured,
      and least able to access health care. Nonetheless, these children demonstrate
      better-than-expected health status, a finding termed "the immigrant paradox" and
      one suggesting that cultural health behaviors among immigrant families might be
      protective in some areas of health. In this article the strength of the immigrant
      paradox, the effect of acculturation on health, and the relationships of
      acculturation, enculturation, language, and literacy skills to health disparities
      are reviewed. The current public policy issues that affect the health disparities
      of children of immigrant families are presented, and a research agenda for
      improving our knowledge about children in immigrant families to develop effective
      interventions and public policies that will reduce their health disparities is
      set forth.

PMID- 19861470
TI  - Conceptualizing child health disparities: a role for developmental neurogenomics.
AB  - Biological, psychological, and social processes interact over a lifetime to
      influence health and vulnerability to disease. Those interested in studying and
      understanding how and why racial/ethnic and social disparities emerge need to
      focus on the intersection of these processes. Recent work exploring molecular
      epigenetic mechanisms of gene expression (in humans as well and other mammalian
      systems) has provided evidence demonstrating that the genome is subject to
      regulation by surrounding contexts (eg, cytoplasmic, cellular, organismic,
      social). The developing stress axis is exquisitely sensitive to regulation by
      social forces represented at the level of the epigenome. Old assumptions about an
      inert genome are simply incorrect. Epigenetic processes may provide the missing
      link that will allow us to understand how social and political conditions, along
      with individual subjective experiences, can directly alter gene expression and
      thereby contribute to observed social inequalities in health. Developmental
      neurogenomics may provide the direct link between the biological and
      social/psychological worlds. These biological mechanisms of plasticity (at the
      level of gene expression and regulation) may play a profound role in how we
      conceptualize health inequalities by informing our concepts regarding the
      somatization or embodiment of social inequalities.

PMID- 19861471
TI  - Confronting social disparities in child health: a critical appraisal of life
      course science and research.
AB  - The utility of the life-course framework to address disparities in child health
      is based on its ability to integrate the science of child development with the
      requirements of effective and just public policy. I argue that the life-course
      framework is best assessed in a historical context and through 4 essential
      observations. First, early genetic and environmental interactions are complex and
      influence outcomes in different settings in very different ways. Second, these
      early-life interactions are themselves subject to considerable later influences
      and, therefore, may not be highly predictive of later outcomes. Third, the
      etiologic nature or timing of early-life interactions does not, per se, determine
      if their life-course effects are amenable to later interventions. Fourth, a
      highly deterministic view of early-life interactions is not supported by the
      science and can generate counterproductive approaches to research and policy
      development. Finally, an alternative approach is proposed on the basis of a
      "human-capacity" model of the life course that connects the search for underlying
      basic mechanisms with a policy-based examination of the comparative effectiveness
      of influences at different developmental stages. This approach suggests an
      expanded research and policy agenda that might be more capable of generating
      urgently needed strategies for reducing disparities in child health. Such an
      approach could ultimately define more comprehensively the power and limits of
      life-course effects in shaping the social distribution of health outcomes in the
      real world.

PMID- 19861472
TI  - Conceptualizing health disparities: panel reflections.

PMID- 19861473
TI  - Devising, implementing, and evaluating interventions to eliminate health care
      disparities in minority children.
AB  - Despite an accumulating body of literature addressing racial/ethnic disparities
      in children's health and health care, there have been few published studies of
      interventions that have been successful in eliminating these disparities. The
      objectives of this article, therefore, are to (1) describe 3 interventions that
      have been successful in eliminating racial/ethnic disparities in children's
      health and health care, (2) highlight tips and pitfalls regarding devising,
      implementing, and evaluating pediatric disparities interventions, and (3) propose
      a research agenda for pediatric disparities interventions. Key characteristics of
      the 3 successful interventions include rigorous study designs; large sample
      sizes; appropriate comparison groups; community-based interventions that are
      culturally and linguistically sensitive and involve collaboration with
      participants; research staff from the same community as the participants;
      appropriate blinding of outcomes assessors; and statistical adjustment of
      outcomes for relevant covariates. On the basis of these characteristics, I
      propose tips, pitfalls, an approach, and a research agenda for devising,
      implementing, and evaluating successful pediatric disparities interventions.
      Examination of 3 successful interventions indicates that pediatric health care
      disparities can be eliminated. Achievement of this goal requires an intervention
      that is rigorous, evidence-based, and culturally and linguistically appropriate.
      The intervention must also include community collaboration, minimize attrition,
      adjust for potential confounders, and incorporate mechanisms for sustainability.

PMID- 19861474
TI  - Health care quality-improvement approaches to reducing child health disparities.
AB  - Relatively few quality-improvement efforts have been aimed at reducing
      differences in children's care and outcomes across race and ethnicity,
      socioeconomic status, and insurance status. To inform quality-improvement efforts
      to reduce child health disparities, we summarize lessons learned from the adult
      disparities-intervention literature, identify interventions that have reduced
      disparities in pediatric asthma outcomes and immunization rates, and outline
      special considerations for child disparity interventions. Key recommendations for
      providers, health care organizations, and researchers include: (1) examine your
      performance data stratified according to insurance status, race/ethnicity,
      language, and socioeconomic status; (2) measure and improve childhood health
      related quality of life, development, and condition-specific targets (such as
      asthma and immunizations); (3) measure and improve anticipatory guidance for
      early prevention of conditions (such as injuries, violence, substance abuse, and
      sexually transmitted diseases) and efforts to promote positive growth (such as
      readership programs to improve low literacy); (4) measure and improve structural
      aspects of care that affect child health outcomes and can reduce disparities,
      such as patient-centered medical-home elements; (5) incorporate families into
      interventions; (6) use multidisciplinary teams with close tracking and follow-up
      of patients; (7) integrate non-health care partners into quality-improvement
      interventions; and (8) culturally tailor quality improvement. A key
      recommendation for payers is to align financial incentives to reduce disparities.
      The National Institutes of Health and other funders should support (1) disparity
      intervention studies on these recommendations that analyze clinical outcomes,
      intervention-implementation processes, and costs, and (2) creation of new child
      health services researchers who can find effective quality-improvement approaches
      for reducing disparities.

PMID- 19861475
TI  - Community engagement and its impact on child health disparities: building blocks,
      examples, and resources.
AB  - National attention to racial and ethnic health disparities has increased over the
      last decades, but marked improvements in minority health, especially among
      children, have been slow to emerge. A life-course perspective with sustained
      community engagement takes into account root causes of poor health in minority
      and low-income communities. This perspective involves a variety of primary care,
      public health, and academic stakeholders. A life-course perspective holds great
      promise for having a positive impact on health inequities. In this article we
      provide background information on available tools and resources for engaging with
      communities. We also offer examples of community-primary care provider
      interventions that have had a positive impact on racial and ethnic health
      disparities. Common elements of these projects are described; additional local
      and national resources are listed; and future research needs, specifically in
      communities around issues that are relevant to children, are articulated.
      Examples throughout the history of pediatrics show the potential to eliminate
      racial and ethnic health disparities not only for children but also for all
      populations across the life course.

PMID- 19861476
TI  - Policy interventions to address child health disparities: moving beyond health
      insurance.
AB  - A full accounting of the excess burden of poor health in childhood must include
      any continuing loss of productivity over the life course. Including these costs
      results in a much higher estimate of the burden than focusing only on medical
      costs and other shorter-run costs to parents (such as lost work time). Policies
      designed to reduce this burden must go beyond increasing eligibility for health
      insurance, because disparities exist not only in access to health insurance but
      also in take-up of insurance, access to care, and the incidence of health
      conditions. We need to create a comprehensive safety net for young children that
      includes automatic eligibility for basic health coverage under Medicaid unless
      parents opt out by enrolling children in a private program; health and nutrition
      services for pregnant women and infants; quality preschool; and home visiting for
      infants and children at risk. Such a program is feasible and would be relatively
      inexpensive.

PMID- 19861477
TI  - Approaches to solving health disparities: panel reflections.

PMID- 19861478
TI  - Starting early: a life-course perspective on child health disparities--research
      recommendations.

PMID- 19861479
TI  - Health literacy and children: introduction.

PMID- 19861480
TI  - Health literacy and child health outcomes: a systematic review of the literature.
AB  - OBJECTIVES: To review the relationship between parent and child literacy and
      child health outcomes and interventions designed to improve child health outcomes
      for children or parents with low literacy skills. METHODS: We searched Medline
      and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for
      articles published from 1980 through 2008 and included studies that reported
      original data, measured literacy and >or=1 health outcome, and assessed the
      relationship between literacy and health outcomes. Health outcomes included
      health knowledge, health behaviors, use of health care resources, intermediate
      markers of disease status, and measures of morbidity. Two abstractors reviewed
      each study for inclusion. Included studies were abstracted into evidence tables
      and were assessed by using an 11-item quality scale. RESULTS: We reviewed 4182
      new titles and abstracts published since 2003. Fifty-eight articles were retained
      for full review, and 13 met the inclusion criteria. Eleven articles from the
      systematic review from 1980 to 2003 met the inclusion criteria, giving us a total
      of 24 articles. Children with low literacy generally had worse health behaviors.
      Parents with low literacy had less health knowledge and had behaviors that were
      less advantageous for their children's health compared with parents with higher
      literacy. Children whose parents had low literacy often had worse health
      outcomes, but we found mixed results for the relationship of literacy to the use
      of health care services. Interventions found that improving written materials can
      increase health knowledge, and combining good written materials with brief
      counseling can improve behaviors including adherence. The average quality of the
      studies was fair to good. CONCLUSIONS: Child and parent literacy seems associated
      with important health outcomes. Future research can help us understand under what
      circumstances this relationship is causal, how literacy and health outcomes are
      related in noncausal pathways, the relative importance of parent and child
      literacy, and what interventions effectively reduce health literacy-related
      disparities.

PMID- 19861481
TI  - Literacy and learning in health care.
AB  - The relationship between literacy and health outcomes are well documented in
      adult medicine, yet specific causal pathways are not entirely clear. Despite an
      incomplete understanding of the problem, numerous interventions have already been
      implemented with variable success. Many of those who proposed earlier strategies
      assumed the problem to originate from reading difficulties only. Given the timely
      need for more effective interventions, it is of increasing importance to
      reconsider the meaning of health literacy to advance our conceptual understanding
      of the problem and how best to respond. One potentially effective approach might
      involve recognizing the known associations between a larger set of cognitive and
      psychosocial abilities with functional literacy skills. Here we review the
      current health literacy definition and literature and draw on relevant research
      from the fields of education, cognitive science, and psychology. In this
      framework, a research agenda is proposed that considers an individual's "health
      learning capacity," which refers to the broad constellation of cognitive and
      psychosocial skills from which patients or family members must draw to
      effectively promote, protect, and manage their own or a child's health. This new,
      related concept will lead, ideally, to more effective ways of thinking about
      health literacy interventions, including the design of health-education
      materials, instructional strategies, and the delivery of health care services to
      support patients and families across the life span.

PMID- 19861482
TI  - Considering children and health literacy: a theoretical approach.
AB  - The theoretical approaches of Paulo Freire, Jean Piaget, and Lev Vygotsky frame
      the consideration of children and health literacy. This article includes a
      general discussion of literacy from the Freirian perspective. A definition of
      health literacy is then presented; first, the established meaning is introduced,
      but then a Freirian extension is proposed. Next, the theories of cognitive
      development by Piaget and Vygotsky are discussed, and examples related to
      children's health literacy are given. Finally, there is a discussion of why it is
      important to encourage and enable health literacy among children and adolescents.

PMID- 19861483
TI  - The health literacy of parents in the United States: a nationally representative
      study.
AB  - OBJECTIVE: To assess the health literacy of US parents and explore the role of
      health literacy in mediating child health disparities. METHODS: A cross-sectional
      study was performed for a nationally representative sample of US parents from the
      2003 National Assessment of Adult Literacy. Parent performance on 13 child health
      related tasks was assessed by simple weighted analyses. Logistic regression
      analyses were performed to describe factors associated with low parent health
      literacy and to explore the relationship between health literacy and self
      reported child health insurance status, difficulty understanding over-the-counter
      medication labeling, and use of food labels. RESULTS: More than 6100 parents made
      up the sample (representing 72600098 US parents); 28.7% of the parents had below
      basic/basic health literacy, 68.4% were unable to enter names and birth dates
      correctly on a health insurance form, 65.9% were unable to calculate the annual
      cost of a health insurance policy on the basis of family size, and 46.4% were
      unable to perform at least 1 of 2 medication-related tasks. Parents with below
      basic health literacy were more likely to have a child without health insurance
      in their household (adjusted odds ratio: 2.4 [95% confidence interval: 1.1-4.9])
      compared with parents with proficient health literacy. Parents with below-basic
      health literacy had 3.4 times the odds (95% confidence interval: 1.6-7.4) of
      reporting difficulty understanding over-the-counter medication labels. Parent
      health literacy was associated with nutrition label use in unadjusted analyses
      but did not retain significance in multivariate analyses. Health literacy
      accounted for some of the effect of education, racial/ethnic, immigrant-status,
      linguistic, and income-related disparities. CONCLUSIONS: A large proportion of US
      parents have limited health-literacy skills. Decreasing literacy demands on
      parents, including simplification of health insurance and other medical forms, as
      well as medication and food labels, is needed to decrease health care access
      barriers for children and allow for informed parent decision-making. Addressing
      low parent health literacy may ameliorate existing child health disparities.

PMID- 19861484
TI  - Pediatricians and health literacy: descriptive results from a national survey.
AB  - OBJECTIVE: To describe pediatricians' self-reported experiences with health
      literacy, use of basic and enhanced communication techniques, and perceived
      barriers to effective communication during office visits. DESIGN/METHODS: A
      national, random sample of 1605 nonretired, posttraining American Academy of
      Pediatrics members were surveyed in 2007 about health literacy and patient
      communication as part of the Periodic Survey of Fellows. The response rate was
      56% (N = 900). RESULTS: Eight-one percent of the pediatricians were aware of a
      situation in the previous 12 months in which a parent had not sufficiently
      understood health information that had been delivered to him or her. In addition,
      44% of all pediatricians were aware of a communication-related error in patient
      care within the previous 12 months. Using simple language (99%), repeating key
      information (92%), and presenting only 2 or 3 concepts at a time (76%) were the
      most commonly used communication strategies. Enhanced communication techniques
      recommended by health literacy experts such as teach-back and indicating key
      points on written educational materials were used less often (23% and 28%,
      respectively). The most common reported barriers to effective communication were
      limited time to discuss information (73%), volume of information (65%), and
      complexity of information (64%). The majority of physicians rated themselves
      highly in their ability to identify caregiver understanding (64%), but only 21%
      rated themselves as very good or excellent in identifying a parent with a
      literacy problem. Fifty-seven percent of the respondents were interested in
      training to improve communication skills, and 58% reported that they would be
      very likely to use easy-to-read written materials, if available from the American
      Academy of Pediatrics. CONCLUSIONS: Pediatricians are aware of health literacy
      related problems and the need for good communication with families but struggle
      with time demands to implement these skills. Despite awareness of communication
      related errors in patient care, pediatricians report underutilizing enhanced
      techniques known to improve communication.

PMID- 19861485
TI  - Health literacy and child health promotion: implications for research, clinical
      care, and public policy.
AB  - The nation's leading sources of morbidity and health disparities (eg, preterm
      birth, obesity, chronic lung disease, cardiovascular disease, type 2 diabetes,
      mental health disorders, and cancer) require an evidence-based approach to the
      delivery of effective preventive care across the life course (eg, prenatal care,
      primary preventive care, immunizations, physical activity, nutrition, smoking
      cessation, and early diagnostic screening). Health literacy may be a critical and
      modifiable factor for improving preventive care and reducing health disparities.
      Recent studies among adults have established an independent association between
      lower health literacy and poorer understanding of preventive care information and
      poor access to preventive care services. Children of parents with higher literacy
      skills are more likely to have better outcomes in child health promotion and
      disease prevention. Adult studies in disease prevention have suggested that
      addressing health literacy would be an efficacious strategy for reducing health
      disparities. Future initiatives to reduce child health inequities should include
      health-promotion strategies that meet the health literacy needs of children,
      adolescents, and their caregivers.

PMID- 19861486
TI  - Health literacy and quality: focus on chronic illness care and patient safety.
AB  - Despite a heightened focus on improving quality, recent studies have suggested
      that children only receive half of the indicated preventive, acute, or chronic
      care. Two major areas in need of improvement are chronic illness care and
      prevention of medical errors. Recently, health literacy has been identified as an
      important and potentially ameliorable factor for improving quality of care.
      Studies of adults have documented that lower health literacy is independently
      associated with poorer understanding of prescriptions and other medical
      information and worse chronic disease knowledge, self-management behaviors, and
      clinical outcomes. There is also growing evidence to suggest that health literacy
      is important in pediatric safety and chronic illness care. Adult studies have
      suggested that addressing literacy can lead to improved patient knowledge,
      behaviors, and outcomes. Early studies in the field of pediatrics have shown
      similar promise. There are significant opportunities to evaluate and demonstrate
      the importance of health literacy in improving pediatric quality of care. Efforts
      to address health literacy should be made to apply the 6 Institute of Medicine
      aims for quality-care that is safe, effective, patient centered, timely,
      efficient, and equitable. Efforts should also be made to consider the distinct
      nature of pediatric care and address the "4 D's" unique to child health: the
      developmental change of children over time; dependency on parents or adults;
      differential epidemiology of child health; and the different demographic patterns
      of children and their families.

PMID- 19861487
TI  - Health literacy and children: recommendations for action.

PMID- 19861488
TI  - Functional reconstruction of NANOS3 expression in the germ cell lineage by a
      novel transgenic reporter reveals distinct subcellular localizations of NANOS3.
AB  - Mutations of RNA-binding proteins such as NANOS3, TIAL1, and DND1 in mice have
      been known to result in the failure of survival and/or proliferation of
      primordial germ cells (PGCs) soon after their fate is specified (around embryonic
      day (E) 8.0), leading to the infertility of these animals. However, the
      mechanisms of actions of these RNA-binding proteins remain largely unresolved. As
      a foundation to explore the role of these RNA-binding proteins in germ cells, we
      established a novel transgenic reporter strain that expresses NANOS3 fused with
      EGFP under the control of Nanos3 regulatory elements. NANOS3-EGFP exhibited
      exclusive expression in PGCs as early as E7.25, and continued to be expressed in
      female germ cells until around E14.5 and in male germ cells throughout the fetal
      period with declining expression levels after E16.5. NANOS3-EGFP resumed strong
      expression in postnatal spermatogonia and continued to be expressed in
      undifferentiated spermatogonial cells in adults. Importantly, the Nanos3-EGFP
      transgene rescued the sterile phenotype of Nanos3 homozygous mutants,
      demonstrating the functional equivalency of NANOS3-EGFP with endogenous NANOS3.
      We found that throughout germ cell development, a predominant amount of NANOS3
      EGFP co-localized with TIAL1 (also known as TIAR) and phosphorylated eukaryotic
      initiation factor 2alpha, markers for the stress granules, whereas a fraction of
      it showed co-localization with DCP1A, a marker for the processing bodies. On the
      other hand, NANOS3-EGFP did not co-localize with Tudor domain-containing protein
      1, a marker for the intermitochondrial cements, in spermatogenic cells. These
      findings unveil the presence of distinct posttranscriptional regulations in PGCs
      soon after their specification, for which RNA-binding proteins such as NANOS3 and
      TIAL1 would play critical functions.

PMID- 19861489
TI  - Replication of the five novel loci for uric acid concentrations and potential
      mediating mechanisms.
AB  - Uric acid (UA) is the final catabolic product of purine metabolism and elevated
      levels are associated with diabetes and cardiovascular disease. A recent meta
      analysis of genome-wide association studies totalling 28,141 participants
      identified five novel loci associated with serum UA levels. In our population
      based cohort of 7795 subjects, we replicated four of these five loci; PDZK1
      (rs12129861, P = 1.07 x 10(-3)), glucokinase regulator protein (GCKR) (rs780094,
      P = 4.83 x 10(-4)), SLC16A9 (rs742132, P = 0.047) and SLC22A11 (rs17300741, P =
      6.13 x 10(-3)), but not LRRC16A (rs742132, P = 0.645). Serum UA concentration is
      a complex trait, closely associated to renal UA handling (fractional UA
      excretion, P < 1 x 10(-300)), renal function (serum creatinine, P < 1 x 10(-300))
      and the metabolic syndrome (including fasting insulin, P = 2.48 x 10(-232);
      insulin resistance, P = 2.51 x 10(-258); waist circumference, P < 1 x 10(-300))
      and systolic blood pressure (P = 1.93 x 10(-219)). Together these factors explain
      67% of the variance in UA levels. Therefore, we sought to determine the potential
      contribution of these factors to the association of these novel loci with UA
      levels, by including them as additional explanatory variables in our analyses,
      and by considering them as alternative response variables. The association with
      the GCKR locus is attenuated by serum triglycerides and fractional UA excretion.
      We also observed the GCKR locus to be associated with total cholesterol (P = 7.52
      x 10(-6)), triglycerides (P = 2.65 x 10(-9)), fasting glucose (P = 0.011),
      fractional UA excretion (P = 3.36 x 10(-5)) and high-sensitive CRP (P = 1.18 x
      10(-3)) also after adjusting for serum UA levels. We argue that GCKR locus
      affects serum UA levels through a factor that also affects triglycerides.

PMID- 19861490
TI  - In vivo analysis of the functions of gamma-tubulin-complex proteins.
AB  - To enhance our understanding of the function(s) of gamma-tubulin-complex proteins
      (GCPs), we identified and analyzed the functions of the Aspergillus nidulans
      homologs of GCP2-GCP6 (here designated GCPB-GCBF). The gamma-tubulin small
      complex (gamma-TuSC) components, gamma-tubulin, GCPB and GCPC, are essential for
      viability and mitotic spindle formation, whereas GCPD-GCPF are not essential for
      viability, spindle formation or sexual reproduction. GCPD-GCPF function in
      reducing the frequency of chromosome mis-segregation and in the assembly of large
      gamma-tubulin complexes. Deletion of any of the gamma-TuSC components eliminates
      the localization of all GCPs to the spindle pole body (SPB), whereas deletion of
      GCPD-GCPF does not affect localization of gamma-TuSC components. Thus, GCPD-GCPF
      do not tether the gamma-TuSC to the SPB, but, rather, the gamma-TuSC tethers them
      to the SPB. GCPD-GCPF exhibit a hierarchy of localization to the SPB. Deletion of
      GCPF eliminates GCPD-GCPE localization to the SPB, and deletion of GCPD
      eliminates GCPE (but not GCPF) localization. All GCPs localize normally in a GCPE
      deletion. We propose a model for the structure of the gamma-tubulin complex and
      its attachment to polar microtubule organizing centers.

PMID- 19861492
TI  - Stat3 promotes directional cell migration by regulating Rac1 activity via its
      activator betaPIX.
AB  - Stat3 is a member of the signal transducer and activator of transcription family,
      which is important for cytokine signaling as well as for a number of cellular
      processes including cell proliferation, anti-apoptosis and immune responses. In
      recent years, evidence has emerged suggesting that Stat3 also participates in
      cell invasion and motility. However, how Stat3 regulates these processes remains
      poorly understood. Here, we find that loss of Stat3 expression in mouse embryonic
      fibroblasts leads to an elevation of Rac1 activity, which promotes a random mode
      of migration by reducing directional persistence and formation of actin stress
      fibers. Through rescue experiments, we demonstrate that Stat3 can regulate the
      activation of Rac1 to mediate persistent directional migration and that this
      function is not dependent on Stat3 transcriptional activity. We find that Stat3
      binds to betaPIX, a Rac1 activator, and that this interaction could represent a
      mechanism by which cytoplasmic Stat3 regulates Rac1 activity to modulate the
      organization of actin cytoskeleton and directional migration.

PMID- 19861491
TI  - Rapid endocytosis provides restricted somatic expression of a K+ channel in
      central neurons.
AB  - Trafficking motifs present in the intracellular regions of ion channels affect
      their subcellular location within neurons. The mechanisms that control
      trafficking to dendrites of central neurons have been identified, but it is not
      fully understood how channels are localized to the soma. We have now identified a
      motif within the calcium-activated potassium channel K(Ca)2.1 (SK1) that results
      in somatic localization. Transfection of hippocampal neurons with K(Ca)2.1
      subunits causes expression of functional channels in only the soma and proximal
      processes. By contrast, expressed K(Ca)2.3 subunits are located throughout the
      processes of transfected neurons. Point mutation of K(Ca)2.1 within this novel
      motif to mimic a sequence present in the C-terminus of K(Ca)2.3 causes expression
      of K(Ca)2.1 subunits throughout the processes. We also demonstrate that blocking
      of clathrin-mediated endocytosis causes K(Ca)2.1 subunit expression to mimic that
      of the mutated subunit. The role of this novel motif is therefore not to directly
      target trafficking of the channel to subcellular compartments, but to regulate
      channel location by subjecting it to rapid clathrin-mediated endocytosis.

PMID- 19861493
TI  - Downregulation of thymosin beta4 in neural progenitor grafts promotes spinal cord
      regeneration.
AB  - Thymosin beta4 (Tbeta4) is an actin-binding peptide whose expression in
      developing brain correlates with migration and neurite extension of neurons.
      Here, we studied the effects of the downregulation of Tbeta4 expression on growth
      and differentiation of murine neural progenitor cells (NPCs), using an antisense
      lentiviral vector. In differentiation-promoting medium, we found twice the number
      of neurons derived from the Tbeta4-antisense-transduced NPCs, which showed
      enhanced neurite outgrowth accompanied by increased expression of the adhesion
      complex N-cadherin-beta-catenin and increased ERK activation. Importantly, when
      the Tbeta4-antisense-transduced NPCs were transplanted in vivo into a mouse model
      of spinal cord injury, they promoted a significantly greater functional recovery.
      Locomotory recovery correlated with increased expression of the regeneration
      promoting cell adhesion molecule L1 by the grafted Tbeta4-antisense-transduced
      NPCs. This resulted in an increased number of regenerating axons and in sprouting
      of serotonergic fibers surrounding and contacting the Tbeta4-antisense-transduced
      NPCs grafted into the lesion site. In conclusion, our data identify a new role
      for Tbeta4 in neuronal differentiation of NPCs by regulating fate determination
      and process outgrowth. Moreover, NPCs with reduced Tbeta4 levels generate an L1
      enriched environment in the lesioned spinal cord that favors growth and sprouting
      of spared host axons and enhances the endogenous tissue-repair processes.

PMID- 19861494
TI  - Frequenin/NCS-1 and the Ca2+-channel alpha1-subunit co-regulate synaptic
      transmission and nerve-terminal growth.
AB  - Drosophila Frequenin (Frq) and its mammalian and worm homologue, NCS-1, are
      Ca(2+)-binding proteins involved in neurotransmission. Using site-specific
      recombination in Drosophila, we created two deletions that removed the entire
      frq1 gene and part of the frq2 gene, resulting in no detectable Frq protein. Frq
      null mutants were viable, but had defects in larval locomotion, deficient
      synaptic transmission, impaired Ca(2+) entry and enhanced nerve-terminal growth.
      The impaired Ca(2+) entry was sufficient to account for reduced neurotransmitter
      release. We hypothesized that Frq either modulates Ca(2+) channels, or that it
      regulates the PI4Kbeta pathway as described in other organisms. To determine
      whether Frq interacts with PI4Kbeta with consequent effects on Ca(2+) channels,
      we first characterized a PI4Kbeta-null mutant and found that PI4Kbeta was
      dispensable for synaptic transmission and nerve-terminal growth. Frq gain-of
      function phenotypes remained present in a PI4Kbeta-null background. We conclude
      that the effects of Frq are not due to an interaction with PI4Kbeta. Using flies
      that were trans-heterozygous for a null frq allele and a null cacophony (encoding
      the alpha(1)-subunit of voltage-gated Ca(2+) channels) allele, we show a
      synergistic effect between these proteins in neurotransmitter release. Gain-of
      function Frq phenotypes were rescued by a hypomorphic cacophony mutation.
      Overall, Frq modulates Ca(2+) entry through a functional interaction with the
      alpha(1) voltage-gated Ca(2+)-channel subunit; this interaction regulates
      neurotransmission and nerve-terminal growth.

PMID- 19861496
TI  - Loss of the mammalian APC/C activator FZR1 shortens G1 and lengthens S phase but
      has little effect on exit from mitosis.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is essential for progression
      through mitosis. At anaphase onset, the APC/C requires the activator protein
      CDC20 to target securin and cyclin B1 for proteasome-dependent degradation, but
      then depends on the CDC20-related protein FZR1 (also known as CDH1) to remain
      active until the onset of the next S phase. To investigate the role of FZR1 in
      mammalian cells, we used RNAi in human cell lines and conditional gene targeting
      in mouse embryonic fibroblasts. In neither case was FZR1 required for exit from
      mitosis, but in cells lacking FZR1, the G1 phase was shortened and the S phase
      was prolonged. In several normal and transformed human cell lines, loss of FZR1
      function induced DNA-damage responses and impaired proliferation independently of
      the p53 status. Constitutive knockdown of p53 in U2OS cells with inducible FZR1
      siRNA also failed to restore their proliferative capacity. Thus, the
      proliferation defects are a direct consequence of the genetic damage inflicted by
      loss of FZR1 function and are largely independent of p53. In summary, mammalian
      FZR1 is not required for the completion of mitosis, but is an important regulator
      of G1 phase and is required for efficient DNA replication in human and mouse
      somatic cells.

PMID- 19861495
TI  - Distinct roles for Crk adaptor isoforms in actin reorganization induced by
      extracellular signals.
AB  - Crk family adaptors, consisting of Src homology 2 (SH2) and SH3 protein-binding
      domains, mediate assembly of protein complexes in signaling. CrkI, an alternately
      spliced form of Crk, lacks the regulatory phosphorylation site and C-terminal SH3
      domain present in CrkII and CrkL. We used gene silencing combined with mutational
      analysis to probe the role of Crk adaptors in platelet-derived growth-factor
      receptor beta (PDGFbetaR) signaling. We demonstrate that Crk adaptors are
      required for formation of focal adhesions, and for PDGF-stimulated remodeling of
      the actin cytoskeleton and cell migration. Crk-dependent signaling is crucial
      during the early stages of PDGFbetaR activation, whereas its termination by Abl
      family tyrosine kinases is important for turnover of focal adhesions and
      progression of dorsal-membrane ruffles. CrkII and CrkL preferentially activate
      the small GTPase Rac1, whereas variants lacking a functional C-terminal SH3
      domain, including CrkI, preferentially activate Rap1. Thus, differences in the
      activity of Crk isoforms, including their effectors and their ability to be
      downregulated by phosphorylation, are important for coordinating dynamic changes
      in the actin cytoskeleton in response to extracellular signals.

PMID- 19861497
TI  - A role for the DNA-damage checkpoint kinase Chk1 in the virulence program of the
      fungus Ustilago maydis.
AB  - During induction of the virulence program in the phytopathogenic fungus Ustilago
      maydis, the cell cycle is arrested on the plant surface and it is not resumed
      until the fungus enters the plant. The mechanism of this cell cycle arrest is
      unknown, but it is thought that it is necessary for the correct implementation of
      the virulence program. Here, we show that this arrest takes place in the G2
      phase, as a result of an increase in the inhibitory phosphorylation of the
      catalytic subunit of the mitotic cyclin-dependent kinase Cdk1. Sequestration in
      the cytoplasm of the Cdc25 phosphatase seems to be one of the reasons for the
      increase in inhibitory phosphorylation. Strikingly, we also report the DNA-damage
      checkpoint kinase Chk1 appears to be involved in this process. Our results
      support the emerging idea that checkpoint kinases have roles other than in the
      DNA-damage response, by virtue of their ability to interact with the cell cycle
      machinery.

PMID- 19861498
TI  - Increased sex chromosome expression and epigenetic abnormalities in spermatids
      from male mice with Y chromosome deletions.
AB  - During male meiosis, the X and Y chromosomes are transcriptionally silenced, a
      process termed meiotic sex chromosome inactivation (MSCI). Recent studies have
      shown that the sex chromosomes remain substantially transcriptionally repressed
      after meiosis in round spermatids, but the mechanisms involved in this later
      repression are poorly understood. Mice with deletions of the Y chromosome long
      arm (MSYq-) have increased spermatid expression of multicopy X and Y genes, and
      so represent a model for studying post-meiotic sex chromosome repression. Here,
      we show that the increase in sex chromosome transcription in spermatids from MSYq
      mice affects not only multicopy but also single-copy XY genes, as well as an X
      linked reporter gene. This increase in transcription is accompanied by specific
      changes in the sex chromosome histone code, including almost complete loss of
      H4K8Ac and reduction of H3K9me3 and CBX1. Together, these data show that an MSYq
      gene regulates sex chromosome gene expression as well as chromatin remodelling in
      spermatids.

PMID- 19861499
TI  - Cayman ataxia protein caytaxin is transported by kinesin along neurites through
      binding to kinesin light chains.
AB  - Deficiency of caytaxin results in hereditary ataxia or dystonia in humans, mice
      and rats. Our yeast two-hybrid screen identified kinesin light chains (KLCs) as
      caytaxin-binding proteins. The tetratricopeptide-repeat region of KLC1 recognizes
      the ELEWED sequence (amino acids 115-120) of caytaxin. This motif is conserved
      among BNIP-2 family members and other KLC-interacting kinesin cargo proteins such
      as calsyntenins. Caytaxin associates with kinesin heavy chains (KHCs) indirectly
      by binding to KLCs, suggesting that caytaxin binds to the tetrameric kinesin
      molecule. In cultured hippocampal neurons, we found that caytaxin is distributed
      in both axons and dendrites in punctate patterns, and it colocalizes with
      microtubules and KHC. GFP-caytaxin expressed in hippocampal neurons is
      transported at a speed ( approximately 1 mum/second) compatible with kinesin
      movement. Inhibition of kinesin-1 by dominant-negative KHC decreases the
      accumulation of caytaxin in the growth cone. Caytaxin puncta do not coincide with
      vesicles containing known kinesin cargos such as APP or JIP-1. A part of
      caytaxin, however, colocalizes with mitochondria and suppression of caytaxin
      expression by RNAi redistributes mitochondria away from the distal ends of
      neurites. These data indicate that caytaxin binds to kinesin-1 and functions as
      an adaptor that mediates intracellular transport of specific cargos, one of which
      is the mitochondrion.

PMID- 19861501
TI  - A model for wetting and evaporation of a post-blink precorneal tear film.
AB  - We examine a fluid dynamic model for the evolution of a precorneal tear film that
      includes evaporation of the aqueous layer and a wetting corneal surface. Our
      model extends previous work on the break-up time for a post-blink tear film to
      include a more realistic model for evaporation. The evaporation model includes
      the effects of conjoining pressure and predicts the existence of an equilibrium
      adsorbed fluid layer that serves as a model for a wetting corneal surface/mucin
      layer. The model allows the prediction of dewetting rates that are compared with
      experimental measurements. By choosing an expected thickness where evaporation
      and conjoining pressure balance, we obtain qualitative agreement for the opening
      rate with in vivo observations.

PMID- 19861500
TI  - Membrane type-1 matrix metalloproteinase activity is regulated by the endocytic
      collagen receptor Endo180.
AB  - The molecular interactions leading to organised, controlled extracellular matrix
      degradation are of central importance during growth, development and tissue
      repair, and when deregulated contribute to disease processes including cancer
      cell invasion. There are two major pathways for collagen degradation: one
      dependent on secreted and membrane-bound collagenases, the other on receptor
      mediated collagen internalisation and intracellular processing. Despite the
      established importance of both pathways, the functional interaction between them
      is largely unknown. We demonstrate here, that the collagen internalisation
      receptor Endo180 (also known as CD280, uPARAP, MRC2) is a novel regulator of
      membrane-bound matrix metalloproteinase (MT1-MMP) activity, MT1-MMP-dependent MMP
      2 activation and urokinase plasminogen activator (uPA) activity. We show close
      correlation between Endo180 expression, collagen accumulation and regulation of
      MT1-MMP cell-surface localisation and activity. We directly demonstrate, using
      collagen inhibition studies and non-collagen-binding mutants of Endo180, that the
      molecular mechanism underlying this regulation is the ability of Endo180 to bind
      and/or internalise collagens, rather than by acting as an interaction partner for
      pro-uPA and its receptor uPAR. These studies strongly support a functional
      interaction between two distinct collagen degradation pathways, define a novel
      mechanism regulating MT1-MMP activity and might have important implications for
      organised collagen clearance in the pericellular environment.

PMID- 19861502
TI  - Targeted gonadotropin-releasing hormone-3 neuron ablation in zebrafish: effects
      on neurogenesis, neuronal migration, and reproduction.
AB  - Hypophysiotropic GnRH neurons are located in the preoptic area and ventral
      hypothalamus of sexually mature vertebrates. In several species, the embryonic
      origin of hypophysiotropic GnRH neurons remains unclear. Using the Tg(GnRH3:EGFP)
      zebrafish line, in which GnRH3 neurons express EGFP, GnRH3 neurons in the
      olfactory region were specifically and individually ablated during early
      development using laser pulses. After ablation, the olfactory region maintained
      the capacity to regenerate GnRH3 neurons. However, this capacity was time
      limited. When ablation of GnRH3 cells was conducted at 2 d after fertilization,
      high regeneration rates were observed, but regeneration capacity significantly
      decreased when ablation was performed at 4 or 6 d after fertilization. Unilateral
      GnRH3 neuron ablation results in unilateral soma presence. These unilateral
      somata are capable of projecting fiber extensions bilaterally. Successful
      bilateral GnRH3 soma ablation during development resulted in complete lack of
      olfactory, terminal nerve, preoptic area, and hypothalamic GnRH3 neurons and
      fibers in 12-wk-old animals. Mature animals lacking GnRH3 neurons exhibited
      arrested oocyte development and reduced average oocyte diameter. Animals in which
      GnRH3 neurons were partially ablated exhibited normal oocyte development;
      however, their fecundity was significantly reduced. These findings demonstrate
      that the hypophysiotropic GnRH3 populations in zebrafish consist of neurons that
      originate in the olfactory region during early development. The presence of GnRH3
      neurons of olfactory region origin in reproductively mature zebrafish is a
      prerequisite for normal oocyte development and reproduction.

PMID- 19861504
TI  - Brain. Editorial.

PMID- 19861503
TI  - Glucose promotes the production of interleukine-1beta and cyclooxygenase-2 in
      mesangial cells via enhanced (Pro)renin receptor expression.
AB  - (Pro)renin receptor (PRR) is present in renal glomeruli, and its expression is up
      regulated in diabetes. Similarly, renal inflammation is increased in the presence
      of hyperglycemia. The linkage between PRR and renal inflammation is not well
      established. We hypothesized that glucose-induced up-regulation of PRR leads to
      increased production of the proinflammatory factors IL-1beta and cyclooxygenase-2
      (COX-2). Studies were conducted in rat mesangial cells (RMCs) exposed to 30 mm D
      glucose for 2 wk followed by PRR small interfering RNA knockdown, IL-1 receptor
      blockade with IL-1 receptor antagonist or angiotensin II type 1 receptor blockade
      with valsartan. The results showed that D-glucose treatment up-regulates
      prorenin, renin, angiotensin II, PRR, IL-1beta, and COX-2 mRNA and protein
      expression and increases phosphorylation of ERK1/2, c-Jun N-terminal kinase, c
      Jun, and nuclear factor-kappaB (NF-kappaB) p65 (serine 276,468 and 536),
      respectively. PRR small interfering RNA attenuated PRR, IL-1beta, and COX-2 mRNA
      and protein expressions and significantly decreased angiotensin II production and
      phosphorylation of ERK1/2 and NF-kappaB p65 associated with high glucose
      exposure. Similarly, IL-1 receptor antagonist significantly reduced COX-2 mRNA
      and protein expression induced by high glucose. COX-2 inhibition reduced high
      glucose-induced PRR expression. We conclude that glucose induces the up
      regulation of PRR and its ligands prorenin and renin, leading to increased IL
      1beta and COX-2 production via the angiotensin II-dependent pathway. It is also
      possible that PRR could enhance the production of these inflammatory cytokines
      through direct stimulation of ERK1/2-NF-kappaB signaling cascade.

PMID- 19861505
TI  - With or without FUS, it is the anatomy that dictates the dementia phenotype.

PMID- 19861506
TI  - Nordihydroguaiaretic Acid from Creosote Bush (Larrea tridentata) Mitigates 12-O
      Tetradecanoylphorbol-13-Acetate-Induced Inflammatory and Oxidative Stress
      Responses of Tumor Promotion Cascade in Mouse Skin.
AB  - Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves
      and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC)
      Coville (creosote bush). It has a long history of traditional medicinal use by
      the Native Americans and Mexicans. The modulatory effects of topically applied
      NDGA was studied on acute inflammatory and oxidative stress responses in mouse
      skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13
      acetate (TPA). Double TPA treatment adversely altered many of the marker
      responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA
      treated mice mitigated cutaneous lipid peroxidation and inhibited production of
      hydrogen peroxide. NDGA treatment also restored reduced glutathione level and
      activities of antioxidant enzymes. Elevated activities of myeloperoxidase,
      xanthine oxidase and skin edema formation in TPA-treated mice were also lowered
      by NDGA indicating a restrained inflammatory response. Furthermore, results of
      histological study demonstrated inhibitory effect of NDGA on cellular
      inflammatory responses. This study provides a direct evidence of antioxidative
      and anti-inflammatory properties of NDGA against TPA-induced cutaneous
      inflammation and oxidative stress corroborating its chemopreventive potential
      against skin cancer.

PMID- 19861507
TI  - Proteomic Analysis of Anti-inflammatory Effects of a Kampo (Japanese Herbal)
      Medicine "Shoseiryuto (Xiao-Qing-Long-Tang)" on Airway Inflammation in a Mouse
      Model.
AB  - Effects of a Kampo (Japanese herbal) medicine "shoseiryuto (SST, xiao-qing-long
      tang in Chinese)", which has been used for the treatment of allergic bronchial
      asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway
      inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally
      administered at 0.5 g kg(-1) day(-1) from day 1 to 6 after OVA inhalation, SST
      reduced the inflammation in lung tissue, the number of eosinophils and the OVA
      specific immunoglobulin E (IgE) antibody titer in bronchoalveolar lavage (BAL)
      fluids at 7 days after the OVA inhalation. SST also reduced the airway
      hyperreactivity at 6 days after the OVA inhalation. Proteomic analysis with the
      agarose two-dimensional electrophoresis showed that the expression of spectrin
      alpha2 was reduced in the lung tissue of OVA-sensitized mice and SST recovered
      the expression. Western blot and immunohistochemical analyses of lung tissue also
      confirmed this result. When prednisolone was orally administered at 3 mg kg(-1)
      day(-1) from day 1 to 6 after OVA inhalation, the inflammation in lung tissue,
      the number of eosinophils in BAL fluids and airway hyperreactivity were reduced
      in the OVA-sensitized mice. However, prednisolone did not reduce the OVA-specific
      IgE antibody titer in BAL fluids and did not recover the expression of spectrin
      alpha2 in lung tissue. These results suggest that at least a part of action
      mechanism of SST against OVA-sensitized allergic airway inflammation in a mouse
      model is different from that of prednisolone.

PMID- 19861508
TI  - The Traditional Japanese Medicine Rikkunshito Promotes Gastric Emptying via the
      Antagonistic Action of the 5-HT(3) Receptor Pathway in Rats.
AB  - The traditional Japanese medicine rikkunshito ameliorates the nitric oxide
      associated delay in gastric emptying. Whether rikkunshito affects gastric
      motility associated with 5-hydroxytryptamine (serotonin: 5-HT) receptors or
      dopamine receptors is unknown. We examined the effects of rikkunshito on the
      delay in gastric emptying induced by 5-HT or dopamine using the phenol red method
      in male Wistar rats. 5-HT (0.01-1.0 mg kg(-1), i.p.) dose dependently delayed
      gastric emptying, similar to the effect of the 5-HT(3) receptor agonist 1-(3
      chlorophenyl) biguanide (0.01-1.0 mg kg(-1), i.p.). Dopamine also dose
      dependently delayed gastric emptying. The 5-HT(3) receptor antagonist ondansetron
      (0.04-4.0 mg kg(-1)) and rikkunshito (125-500 mg kg(-1)) significantly suppressed
      the delay in gastric emptying caused by 5-HT or 1-(3-chlorophenyl) biguanide.
      Hesperidin (the most active ingredient in rikkunshito) suppressed the 5-HT
      induced delayed gastric emptying in a dose-dependent manner, the maximum effect
      of which was similar to that of ondansetron (0.4 mg kg(-1)). The improvement
      obtained by rikkunshito or ondansetron in delaying gastric emptying was
      completely blocked by pretreatment with atropine. Rikkunshito appears to improve
      delay in gastric emptying via the antagonistic action of the 5-HT(3) receptor
      pathway.

PMID- 19861509
TI  - Agaricus blazei Extract Induces Apoptosis through ROS-Dependent JNK Activation
      Involving the Mitochondrial Pathway and Suppression of Constitutive NF-kappaB in
      THP-1 Cells.
AB  - Agaricus blazei is widely accepted as a traditional medicinal mushroom, and it
      has been known to exhibit immunostimulatory and anti-cancer activity. However,
      the apoptotic mechanism in cancer cells is poorly understood. In this study, we
      have investigated whether A. blazei extract (ABE) exerts antiproliferative and
      apoptotic effects in human leukemic THP-1 cells. We observed that ABE-induced
      apoptosis is associated with the mitochondrial pathway, which is mediated by
      reactive oxygen species (ROS) generation and prolonged c-Jun N-terminal kinase
      (JNK) activation. In addition, the ABE treatment resulted in the accumulation of
      cytochrome c in the cytoplasm, an increase in caspase activity, and an
      upregulation of Bax and Bad. With those results in mind, we found that ABE
      decreases constitutive NF-kappaB activation and NF-kappaB-regulated gene products
      such as IAP-1 and -2. We concluded that ABE induces apoptosis with ROS-dependent
      JNK activation and constitutive activated NF-kappaB inhibition in THP-1 cells.

PMID- 19861510
TI  - Incidence of carcinoma of the major salivary glands according to the WHO
      classification, 1992 to 2006: a population-based study in the United States.
AB  - BACKGROUND: Carcinomas of the major salivary glands (M-SGC) comprise a
      morphologically diverse group of rare tumors of largely unknown cause. To gain
      insight into etiology, we evaluated incidence of M-SGC using the WHO
      classification schema (WHO-2005). METHODS: We calculated age-adjusted incidence
      rates (IR) and IR ratios (IRR) for M-SGC diagnosed between 1992 and 2006 in the
      Surveillance, Epidemiology and End Results Program. RESULTS: Overall, 6,391 M-SGC
      (IR, 11.95/1,000,000 person-years) were diagnosed during 1992 to 2006. Nearly 85%
      of cases (n = 5,370; IR, 10.00) were encompassed within WHO-2005, and among
      these, males had higher IRs than females [IRR, 1.51; 95% confidence interval (95%
      CI), 1.43-1.60]. Squamous cell (IR, 3.44) and mucoepidermoid (IR, 3.23)
      carcinomas occurred most frequently among males, whereas mucoepidermoid (IR,
      2.67), acinic cell (IR, 1.57), and adenoid cystic (IR, 1.40) carcinomas were most
      common among females. Mucoepidermoid, acinic cell, and adenoid cystic carcinomas
      predominated in females through age approximately 50 years; thereafter, IRs of
      acinic cell and adenoid cystic carcinomas were nearly equal among females and
      males, whereas IRs of mucoepidermoid carcinoma among males exceeded IRs among
      females (IRR, 1.57; 95% CI, 1.38-1.78). Except for mucoepidermoid and adenoid
      cystic carcinomas, which occurred equally among all races, other subtypes had
      significantly lower incidence among Blacks and Asians/Pacific Islanders than
      among Whites. Adenoid cystic carcinoma occurred equally in the submandibular and
      parotid glands, and other M-SGC histologic subtypes evaluated had 77% to 98%
      lower IRs in the submandibular gland. Overall M-SGC IRs remained stable during
      1992 to 2006. CONCLUSION: Distinct incidence patterns according to histologic
      subtype suggest that M-SGC are a diverse group of neoplasms characterized by
      etiologic and/or biological heterogeneity with varying susceptibility by gender
      and race.

PMID- 19861511
TI  - Effects of vitamin d and calcium on proliferation and differentiation in normal
      colon mucosa: a randomized clinical trial.
AB  - To investigate the potential efficacy of calcium and vitamin D in reducing risk
      for colorectal neoplasms and to develop "treatable" phenotypic biomarkers of risk
      for colorectal neoplasms, we conducted a pilot, randomized, double-blind, placebo
      controlled, 2 x 2 factorial clinical trial to test the effects of these agents on
      cell cycle markers in the normal colorectal mucosa. Ninety-two men and women with
      at least one pathology-confirmed colorectal adenoma were treated with 2 g/day
      calcium and/or 800 IU/day vitamin D(3) versus placebo over 6 months. Overall
      expression and distributions of p21(waf1/cip1) (marker of differentiation), MIB-1
      (marker of short-term proliferation), and hTERT (marker of long-term
      proliferation) in colorectal crypts in the normal-appearing rectal mucosa were
      detected by automated immunohistochemistry and quantified by image analysis. In
      the calcium, vitamin D, and calcium plus vitamin D groups relative to the
      placebo, p21 expression increased by 201% (P = 0.03), 242% (P = 0.005), and 25%
      (P = 0.47), respectively, along the full lengths of colorectal crypts after 6
      months of treatment. There were no statistically significant changes in the
      expression of either MIB-1 or hTERT in the crypts overall; however, the
      proportion of hTERT, but not MIB-1, expression that extended into the upper 40%
      of the crypts was reduced by 15% (P = 0.02) in the vitamin D plus calcium group
      relative to the placebo. These results indicate that calcium and vitamin D
      promote colorectal epithelial cell differentiation and may "normalize" the
      colorectal crypt proliferative zone in sporadic adenoma patients, and support
      further investigation of calcium and vitamin D as chemopreventive agents against
      colorectal neoplasms.

PMID- 19861512
TI  - The relation of serum parathyroid hormone and serum calcium to serum levels of
      prostate-specific antigen: a population-based study.
AB  - Experimental and clinical data implicate calcium and parathyroid hormone (PTH) in
      the development of prostate cancer. However, epidemiologic data on the role of
      these variables in prostate health are sparse. We examined the relationship
      between serum levels of calcium, PTH, and prostate-specific antigen (PSA), an
      established marker of prostate growth, in a large, population-based study using
      multivariate linear regression. We studied 1,273 men in National Health and
      Nutrition Survey 2005 to 2006 who were >or=40 years of age and who were without
      clinical prostate cancer. Adjusted for age, race, body mass index, and serum
      levels of 25-hydroxyvitamin D, serum levels of PTH were significantly positively
      correlated with serum PSA (P = 0.01). Serum levels of PTH and calcium each were
      correlated significantly with free PSA (P = 0.05 and 0.008, respectively). The
      percentage of men who had elevated serum levels of PTH (PTH, >or=66 pg/mL) was
      significantly greater among African American men (19.2 versus 9.6%, P = 0.04).
      Compared with men whose PTH was at the lower end of the reference range, the
      predicted PSA for men with a PTH of 66 pg/mL was increased 43%. These findings
      support the hypothesis that serum calcium and serum PTH stimulate prostate growth
      in men without clinical prostate cancer and have implications for the use of PSA
      as a screening tool for prostate cancer.

PMID- 19861513
TI  - Association between lifestyle factors and CpG island methylation in a cancer-free
      population.
AB  - BACKGROUND: Many risk factors have been associated with cancer, such as age,
      family history, race, smoking, high-fat diet, and poor nutrition. It is important
      to reveal the molecular changes related to risk factors that could facilitate
      early detection, prevention, and overall control of cancer. METHODS: We selected
      six cancer-specific methylated genes that have previously been reported in
      primary tumors and have also been detected in different bodily fluids of cancer
      patients. Here, we used quantitative fluorogenic real-time methylation-specific
      PCR in plasma DNA samples for the detection of methylation changes from an
      asymptomatic population who do not have any known cancer. RESULTS: The promoter
      methylation frequencies of the studied genes were as follows: APC (7%), CCND2
      (22%), GSTP1 (2%), MGMT (9%), RARbeta2 (29%), and P16 (3%). Promoter methylation
      of at least one of the genes analyzed was observed in approximately 46% (72 of
      157) of the samples by binary dichotomization. Promoter hypermethylation of at
      least two genes was detected in 17% (26 of 157) of the samples. RARbeta2
      methylation was observed in 45% of subjects who had a high-fat diet in contrast
      with those who had a low-fat diet (23%; P = 0.007). DISCUSSION: Our findings may
      help to elucidate early methylation changes that may lead to cancer development.
      These methylation changes could be due to exposure to risk factors and may be
      useful for cancer prevention measures such as changes in lifestyle. Longitudinal
      follow-up of a high-risk population is needed to understand the association of
      methylation of candidate genes in cancer development.

PMID- 19861514
TI  - Telomere length in peripheral leukocyte DNA and gastric cancer risk.
AB  - Telomere length reflects lifetime cumulative oxidative stress from environmental
      exposures, such as cigarette smoking and chronic inflammation. Shortened telomere
      length is thought to cause genomic instability and has been associated with
      several cancers. We examined the association of telomere length in peripheral
      leukocyte DNA with gastric cancer risk as well as potential confounding factors
      and risk modifiers for telomere length-related risk. In a population-based study
      of gastric cancer conducted in a high-risk population in Warsaw, Poland, between
      1994 and 1996, we measured relative telomere length in 300 cases and 416 age- and
      gender-matched controls using quantitative real-time PCR. Among controls,
      telomeres were significantly shorter in association with aging (P < 0.001),
      increasing pack-years of cigarette smoking (P = 0.02), decreasing fruit intake (P
      = 0.04), and Helicobacter pylori positivity (P = 0.03). Gastric cancer cases had
      significantly shorter telomere length (mean +/- SD relative telomere length, 1.25
      +/- 0.34) than controls (1.34 +/- 0.35; P = 0.0008). Gastric cancer risk doubled
      [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.33-3.13] among
      subjects in the shortest compared with the highest quartile of telomere length
      (P(trend) < 0.001). Telomere length-associated risks were higher among
      individuals with the lowest risk profile, those H. pylori-negative (OR, 5.45; 95%
      CI, 2.10-14.1), nonsmokers (OR, 3.07; 95% CI, 1.71-5.51), and individuals with
      high intake of fruits (OR, 2.43; 95% CI, 1.46-4.05) or vegetables (OR, 2.39; 95%
      CI, 1.51-3.81). Our results suggest that telomere length in peripheral leukocyte
      DNA was associated with H. pylori positivity, cigarette smoking, and dietary
      fruit intake. Shortened telomeres increased gastric cancer risk in this high-risk
      Polish population.

PMID- 19861515
TI  - Identifying genes for establishing a multigenic test for hepatocellular carcinoma
      surveillance in hepatitis C virus-positive cirrhotic patients.
AB  - In this study, we used the Affymetrix HG-U133A version 2.0 GeneChips to identify
      genes capable of distinguishing cirrhotic liver tissues with and without
      hepatocellular carcinoma by modeling the high-dimensional dataset using an L(1)
      penalized logistic regression model, with error estimated using N-fold cross
      validation. Genes identified by gene expression microarray included those that
      have important links to cancer development and progression, including VAMP2,
      DPP4, CALR, CACNA1C, and EGR1. In addition, the selected molecular markers in the
      multigenic gene expression classifier were subsequently validated using reverse
      transcriptase-real time PCR, and an independently acquired gene expression
      microarray dataset was downloaded from Gene Expression Omnibus. The multigenetic
      classifier derived herein did similarly or better than standard abdominal
      ultrasonography and serum alpha-fetoprotein, which are currently used for
      hepatocellular carcinoma surveillance. Because early hepatocellular carcinoma
      diagnosis increases survival by increasing access to therapeutic options, these
      molecular markers may prove useful for early diagnosis of hepatocellular
      carcinoma, especially if prospectively validated and translated into gene
      products that can be reproducibly and reliably tested noninvasively.

PMID- 19861516
TI  - Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on
      invasive breast cancer.
AB  - BACKGROUND: Breast cancer concern is a major reason for the recent marked
      reduction in use of postmenopausal hormone therapy, although equally effective
      means of controlling menopausal symptoms are lacking. Single nucleotide
      polymorphisms (SNP) in the fibroblast growth factor receptor 2 (FGFR2) gene are
      substantially associated with postmenopausal breast cancer risk and could
      influence hormone therapy effects. PARTICIPANTS AND METHODS: We interrogated
      eight SNPs in intron 2 of the FGFR2 gene for 2,166 invasive breast cancer cases
      from the Women's Health Initiative clinical trial and one-to-one matched controls
      to confirm an association with breast cancer risk. We used case-only analyses to
      examine the dependence of estrogen plus progestin and estrogen-alone odds ratios
      on SNP genotype. RESULTS: Seven FGFR2 SNPs, including six in a single linkage
      disequilibrium region, were found to associate strongly (P < 10(-7)) with breast
      cancer risk. SNP rs3750817 (minor allele T with frequency 0.39) had an estimated
      per-minor-allele odds ratio of 0.78, and was not in such strong linkage
      disequilibrium with the other SNPs. The genotype of this SNP related
      significantly (P < 0.05) to hormone therapy odds ratios. For estrogen plus
      progestin, the odds ratios (95% confidence intervals) at 0, 1, and 2 minor SNP
      alleles were 1.52 (1.14-2.02), 1.33 (1.01-1.75), and 0.69 (0.41-1.17), whereas
      the corresponding values for estrogen alone were 0.74 (0.51-1.09), 0.99 (0.68
      1.44), and 0.34 (0.15-0.76). CONCLUSIONS: Postmenopausal women having TT genotype
      for SNP rs3750817 have a reduced breast cancer risk and seem to experience
      comparatively favorable effects of postmenopausal hormone therapy.

PMID- 19861517
TI  - Predisposition for TMPRSS2-ERG fusion in prostate cancer by variants in DNA
      repair genes.
AB  - The somatic fusion of TMPRSS2 to ETS oncogenes is a common event in prostate
      cancer (PCa). We hypothesized that defects in DNA repair may lead to an increase
      of chromosomal rearrangements and thus to the occurrence of ETS oncogene fusion.
      We have previously conducted a genome-wide linkage analysis in TMPRSS2-ERG fusion
      positive PCa families, revealing potential susceptibility loci on chromosomes
      5q14, 9q21, 10q26, 11q24, 12q15, 13q12, 18q, and Xq27. In the present study, nine
      candidate genes from these regions were selected from the context of DNA repair
      and screened for mutations in TMPRSS2-ERG fusion-positive families. Thirteen
      nonsynonymous variants, 5 of which had a minor allele frequency of <0.05, were
      genotyped in 210 familial cases, 47 of which with a known TMPRSS2-ERG status, 329
      sporadic cases, and 512 controls. Significant association of TMPRSS2-ERG fusion
      positive PCa was found with rare variants in the genes for POLI [variant F532S: P
      = 0.0011; odds ratios (OR), 4.62; 95% confidence interval (95% CI), 1.84-11.56]
      and ESCO1 (variant N191S: P = 0.0034; OR, 4.27; 95% CI, 1.62-11.28). Additional
      findings, regardless of TMPRSS2-ERG status, were the overrepresentation of a rare
      BRCA2 variant (V2728I: P = 0.03; OR, 6.16; 95% CI, 1.19-32.00) in familial PCa
      and of a common allele of RMI1 (variant N455S: P = 0.02; OR, 1.33; 95% CI, 1.04
      1.70) in unselected PCa cases. The DNA repair genes POLI and ESCO1 are proposed
      as susceptibility genes for TMPRSS2-ERG fusion-positive PCa that warrant further
      investigation.

PMID- 19861518
TI  - Diindolylmethane inhibits cervical dysplasia, alters estrogen metabolism, and
      enhances immune response in the K14-HPV16 transgenic mouse model.
AB  - This study was designed to establish whether 3,3'-diindolylmethane (DIM) can
      inhibit cervical lesions, alter estrogen metabolism in favor of C-2
      hydroxylation, and enhance immune function in the K14-HPV16 transgenic mouse
      model. Mice were bred, genotyped, implanted with E(2) pellets (0.25 mg/90-day
      release) under anesthesia, and divided into groups. Wild-type and transgenic mice
      were given either AIN76A diet alone or with 2,000 ppm DIM for 12 weeks. Blood and
      reproductive tracts were obtained. Blood was analyzed for estrogen metabolites
      and IFN-gamma. The cervical transformation zone was sectioned and stained for
      histology. Estradiol C-2 hydroxylation and serum IFN-gamma levels were
      significantly increased over controls in wild-type and transgenic mice receiving
      DIM. In wild-type mice without DIM, hyperplasia of the squamous epithelium was
      observed. Wild-type mice fed DIM displayed a normal thin epithelium. In
      transgenic mice without DIM, epithelial cell projections into the stroma
      (papillae) were present. An additional degree of nuclear anaplasia in the stratum
      espinosum was observed. Dysplastic cells were present. Transgenic mice fed DIM
      displayed some mild hyperplasia of the squamous epithelium. DIM increases
      estrogen C-2 hydroxylation in this model. Serum INF-gamma was increased,
      indicating increased immune response in the DIM-fed animals. Histopathology
      showed a marked decrease in cervical dsyplasia in both wild-type and transgenic
      mice, indicating that DIM delays or inhibits the progression from cervical
      dysplasia to cervical cancer. Using the K14-HPV16 transgenic mouse model, we have
      shown that DIM inhibits the development of E6/E7 oncogene-induced cervical
      lesions.

PMID- 19861519
TI  - Genetic variants in the vitamin d receptor are associated with advanced prostate
      cancer at diagnosis: findings from the prostate testing for cancer and treatment
      study and a systematic review.
AB  - Low levels of plasma vitamin D have been implicated as a possible risk factor for
      both prostate cancer incidence and advanced disease, and recent phase II trials
      suggest that vitamin D supplementation might delay progression of prostate
      cancer. Common polymorphisms in the vitamin D receptor (VDR) are associated with
      VDR activity and are therefore potentially useful proxies for assessing whether
      vitamin D is causally related to advanced prostate cancer. We genotyped five well
      known VDR polymorphisms in 1,604 men with prostate cancer from the Prostate
      Testing for Cancer and Treatment study. Our aim was to examine the association
      between VDR polymorphisms and cancer stage (localized versus advanced) as well as
      cancer grade (Gleason score <7 versus >or=7). Moreover, we also carried out a
      systematic review and meta-analysis of 13 similar studies. As a result of our
      meta-analysis, we revealed three polymorphisms, BsmI, ApaI, and TaqI, associated
      with high Gleason score with an overall summary odds ratios (95% confidence
      intervals) of 1.12 (1.00-1.25; bb versus BB + Bb), 1.25 (1.02-1.53; aa versus AA
      + Aa), and 0.82 (0.69-0.98; Tt + tt versus TT), respectively. The haplotype
      analysis revealed that the BsmI (B)-ApaI (A)-TaqI (t) participants compared with
      BsmI (b)-ApaI (a)-TaqI (T) individuals were less likely to have high Gleason
      scores (odds ratio, 0.84; 95% confidence interval, 0.71-1.00; P(unadjusted) =
      0.050; P(adjusted) = 0.014). Our finding provides some support for the hypothesis
      that low levels of vitamin D may increase the risk of prostate cancer
      progression.

PMID- 19861520
TI  - Nutrient dietary patterns and gastric cancer risk in Italy.
AB  - BACKGROUND: There have been several studies on diet and gastric cancer, but only
      a few investigations have considered the role of dietary patterns. METHODS: We
      investigated gastric cancer risk in relation to dietary patterns in a case
      control study conducted in northern Italy between 1997 and 2007, including 230
      patients with incident, histologically confirmed gastric cancer and 547 frequency
      matched controls, admitted to the same hospitals as cases, with acute
      nonneoplastic conditions. Dietary habits were investigated through a validated
      food frequency questionnaire including 78 foods and beverages. We identified a
      posteriori dietary patterns on a selected set of 28 micro- and macro-nutrients
      through an exploratory principal component factor analysis. We estimated the odds
      ratios (OR) and the corresponding 95% confidence intervals (95% CI) using
      conditional logistic regression models on quartiles of factor scores. RESULTS: We
      identified four major dietary patterns, named "animal products", "vitamins and
      fiber", "vegetable unsaturated fatty acids", and "starch-rich". We observed a
      positive association between gastric cancer risk and the "animal products" (OR,
      2.13; 95% CI, 1.34-3.40, for the highest versus the lowest score quartile) and
      the "starch-rich" (OR, 1.67; 95% CI, 1.01-2.77) dietary patterns. The "vitamins
      and fiber" pattern (OR, 0.60; 95% CI, 0.37-0.99) was inversely associated with
      gastric cancer, whereas no significant association emerged with the "vegetable
      unsaturated fatty acids" pattern (OR, 0.89; 95% CI, 0.56-1.42). CONCLUSIONS: Our
      analysis suggests a protective effect against gastric cancer risk of dietary
      patterns rich in fruits and vegetables, and a positive association of dietary
      patterns rich in meats and animal fats and starchy foods.

PMID- 19861521
TI  - Efficacy of skin self-examination practices for early melanoma detection.
AB  - Although skin self-examination (SSE) may increase rates of early melanoma
      detection, the efficacy of different SSE practices has not been thoroughly
      studied. We examined associations between SSE practices and tumor thickness in
      patients with recently diagnosed melanoma. METHODS: 321 melanoma patients at
      three hospitals completed questionnaires on demographics and SSE practices.
      Patient-reported SSE was measured by routine examination of 13 specific body
      areas, frequency of mole examination, and use of a melanoma picture aid to assist
      with SSE. Histologic diagnoses and Breslow depth were confirmed by
      dermatopathologists. Regression analyses were used to calculate ratios of
      geometric mean tumor thickness and odds ratios for having thicker versus thinner
      tumors for different SSE behaviors. RESULTS: Rates of SSE varied considerably by
      SSE item. Patients routinely examining at least some of their skin had thinner
      melanomas [adjusted geometric mean tumor ratio, 0.73; 95% confidence interval
      (95% CI), 0.50-0.94]. Frequency of mole examination did not predict tumor
      thickness. Using a melanoma picture as a SSE aid was strongly associated with
      reduced tumor thickness (adjusted ratio, 0.75; 95% CI, 0.66-0.85 for ever versus
      never use). A composite measure of thoroughness of SSE was the best predictor of
      thickness (adjusted ratio, 0.58; 95% CI, 0.36-0.75) for high versus low
      thoroughness. CONCLUSIONS: SSE was associated with decreased tumor thickness by
      most measures. However, the diverse rates of SSE practices and the distinct
      associations between these practices and melanoma thickness suggest a complexity
      in SSE that should be addressed in future studies. SSE should be evaluated by
      more than one measure.

PMID- 19861522
TI  - Dietary patterns and prostate cancer risk.
AB  - Recent studies report that certain dietary patterns, especially those high in red
      and processed meats, are associated with prostate cancer risk. We prospectively
      investigated associations between empirically derived dietary patterns and
      prostate cancer risk using the Melbourne Collaborative Cohort Study. We followed
      14,627 men of ages 34 to 75 years for an average of 13.6 years, and identified
      1,018 incident prostate cancers. Factor analysis of the 121-item food frequency
      questionnaire identified four factors with eigenvalues >2 that explained 67% of
      the total variance. Using Cox proportional hazard models, we found no association
      between any dietary pattern and prostate cancer risk overall (all P(trend) >or=
      0.2). The hazard ratios for quartiles of the dietary pattern scores ranged from
      0.87 to 1.14 and all 95% confidence intervals included 1. The analyses by
      aggressiveness, Gleason score groups, and age at diagnosis did not show any
      association (all P(trend) > 0.07).

PMID- 19861523
TI  - DNA hypermethylation of ESR1 and PGR in breast cancer: pathologic and
      epidemiologic associations.
AB  - Improved understanding of the etiology of estrogen receptor-alpha (ERalpha)
      negative and progesterone receptor (PR)-negative breast cancers may permit
      improved risk prediction. In vitro studies implicate DNA hypermethylation of the
      ERalpha and PR promoters in the pathogenesis of ERalpha-negative and PR-negative
      tumors, but results are not definitive. We evaluated 200 invasive breast cancers
      selected from a population-based case-control study. DNA extracted from fixed
      tumor tissue cores was tested using MethyLight to assess DNA methylation at four
      CpG islands: ESR1 promoters A and B; PGR promoters A and B; and a CpG shore, ESR1
      promoter C. DNA methylation results were compared with levels of ERalpha and PR,
      tumor characteristics, and breast cancer risk factors. We observed mild to
      moderate DNA methylation levels in most tumors for ESR1 promoters A and B and PGR
      promoter B, and a few tumors showed mild methylation in PGR promoter A. In
      contrast, ESR1 promoter C showed a wide range of methylation and was weakly
      correlated with lower expression levels of ERalpha (beta = -0.26; P < 0.0001) and
      PR (beta = -0.25; P < 0.0001). The percentage of tumors with methylated PGR
      promoters A and B was significantly higher for tumors with low ERalpha (A,
      Fisher's test P = 0.0001; B, P = 0.033) and PR levels (A, P = 0.0006; B, P =
      0.001). Our data suggest that the relationships between DNA methylation of ESR1
      and PGR promoters and protein expression are weak and unlikely to represent a
      predominant mechanism of receptor silencing. In contrast to CpG islands, ESR1
      promoter C showed a wider range of methylation levels and inverse associations
      with ERalpha and PR expression.

PMID- 19861524
TI  - Colorectal mucosal expression of MSH2 as a potential biomarker of risk for
      colorectal neoplasms.
AB  - To characterize the expression of the mismatch repair gene MSH2 in normal
      colorectal crypts in humans and assess parameters of its expression as a
      potential modifiable biomarker of risk for colorectal neoplasms, we conducted a
      pilot, colonoscopy-based case-control study (51 cases and 154 controls) of
      incident, sporadic colorectal adenoma. Biopsies of normal-appearing rectal,
      sigmoid, and ascending colon mucosa were procured, immunohistochemically
      processed for MSH2 protein, and analyzed using custom quantitative image analysis
      procedures. MSH2 expression in adenoma cases was lower than in controls by 49% (P
      = 0.01) and 23% (P = 0.06) in the ascending colon and rectum, respectively, but
      not in the sigmoid colon. MSH2 expression in the rectum was 39% (P = 0.04) higher
      in subjects who regularly took a nonsteroidal anti-inflammatory drug than in
      those who did not, and it tended to be lower in those with adenomas in the right
      colon and those who had an adenoma with more advanced characteristics. These
      preliminary data suggest that lower MSH2 expression in the normal colonic mucosa,
      at least in the ascending colon and rectum, may be associated with increased risk
      of incident, sporadic colorectal adenoma as well as with modifiable risk factors
      for colorectal neoplasms, thus supporting further investigation of MSH2
      expression as a potential modifiable biomarker of risk for colorectal neoplasms.

PMID- 19861526
TI  - Human papillomavirus 16 load and E2/E6 ratio in HPV16-positive women: biomarkers
      for cervical intraepithelial neoplasia >or=2 in a liquid-based cytology setting?
AB  - This retrospective case-control study assessed human papillomavirus 16 (HPV16)
      viral load and E2/E6 ratio as risk markers for cervical intraepithelial neoplasia
      (CIN) >or=2 lesions in HPV16-positive women in a routine liquid-based cytology
      setting. Triplex quantitative PCR for HPV16 E6, E2, and beta-globin was done to
      determine the HPV16 load and the E2/E6 ratio, as a surrogate marker for
      integration, for women with a negative histologic endpoint (200 controls: 83
      normal histology and 117 CIN1) and women with a >or=CIN2 endpoint (180 cases: 41
      CIN2, 122 CIN3, and 17 invasive carcinoma). Our analysis showed a significantly
      higher HPV16 load in the case group, which was completely attributable to the
      high viral load of samples with invasive carcinoma as histologic endpoint. There
      was no significant difference in viral load between the other histologic groups.
      The E2/E6 ratio proved to be lower for the cases. However, the E2/E6 ratio
      indicated the presence of HPV integration in a considerable amount of control
      samples (44.3%), which suggests that HPV integration occurs early in the
      development of cancer and undermines the clinical value of viral integration.
      Overall, the intrinsic heterogeneous nature of the cervical cytology samples
      caused a substantial overlap of the HPV16 load and the E2/E6 ratio between
      controls and cases, which precludes the determination of cutoff values for risk
      prediction and hampers the clinical applicability in a cervical screening
      setting.

PMID- 19861525
TI  - Urinary prostaglandin E2 metabolite and gastric cancer risk in the Shanghai
      women's health study.
AB  - Chronic inflammation has been implicated in the etiology of gastric cancer.
      Prostaglandin E(2) (PGE(2)) is one of the major end-products of the
      cyclooxygenase-2 pathway, an enzyme that is an important mediator of
      inflammation. Using a novel method of quantifying the primary urinary metabolite
      of PGE(2) (PGE-M; 11alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranorprostane-1,20-dioic
      acid), we evaluated urinary PGE-M concentrations in association with subsequent
      risk of development of gastric cancer in the Shanghai Women's Health Study, a
      large population-based prospective cohort, using a nested case-control study
      design. Controls were matched (1:1) to 153 gastric cancer cases by menopausal
      status; age, time, and date of sample collection; time interval since last meal;
      and availability of urine sample. Odds ratios (95% confidence intervals) were
      calculated using conditional logistic regression adjusted for potential
      confounders. Baseline urinary PGE-M levels were slightly higher among gastric
      cancer cases with a median of 6.4 ng/mg creatinine (interquartile range, 3.4
      11.2) compared with 5.4 ng/mg creatinine among controls (interquartile range, 2.8
      9.0), but this difference was not statistically significant (P = 0.34, Wilcoxon).
      With increasing quartiles of urinary PGE-M levels, the odds ratios (95%
      confidence intervals) for risk of gastric cancer increased in quartiles 2 to 4:
      1.00 (0.48-2.08), 1.40 (0.67-2.91), and 1.98 (0.95-4.13), with a statistically
      significant test for trend (P = 0.04). The association persisted after additional
      adjustment for Helicobacter pylori status and was slightly strengthened among non
      nonsteroidal anti-inflammatory drug users, subjects with positive H. pylori
      status, and for cases diagnosed within 46 months after study enrollment. Our
      findings suggest that higher levels of urinary PGE-M, a marker of inflammation,
      may be associated with gastric cancer risk.

PMID- 19861527
TI  - Impact of multiple alcohol dehydrogenase gene polymorphisms on risk of upper
      aerodigestive tract cancers in a Japanese population.
AB  - Alcohol intake is positively associated with the risk of upper aerodigestive
      tract (UAT) cancer. The genes that encode alcohol-metabolizing enzymes, primarily
      alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH), are polymorphic.
      In Caucasians, significant associations between polymorphisms in ADH1B
      (rs1229984) and ADH1C (rs698 and rs1693482), and UAT cancer have been observed,
      despite strong linkage disequilibrium among them. Moreover, UAT cancer was
      significantly associated with rs1573496 in ADH7, and not with rs1984362 in ADH4.
      However, little evidence is available concerning ADH4 or ADH7 polymorphisms in
      Asian populations. We conducted a matched case-control study to clarify the role
      of ADH polymorphisms in a Japanese population. Cases and controls were 585
      patients with UAT cancer and 1,170 noncancer outpatients. Genotyping for ADHs and
      ALDH2 was done using TaqMan assays. Associations between polymorphisms and UAT
      cancer were assessed by odds ratios and 95% confidence intervals using
      conditional logistic regression models that adjusted for age, sex, smoking,
      drinking, and ALDH2. Adjusted odds ratios were significant for rs4148887 and
      rs3805322 in ADH4, rs1229984 in ADH1B, rs698 and rs1693482 in ADH1C, and
      rs284787, rs1154460, and rs3737482 in ADH7. We also observed that ADH7 rs3737482
      and ADH4 rs4148887 had independently and statistically significant effects on UAT
      cancer. The magnitude of effect of these ADH polymorphisms was greater in
      subjects who were heavy drinkers, heavy smokers, and had esophageal cancer. These
      findings show that multiple ADH gene polymorphisms were associated with UAT
      cancer in this Japanese population. Further studies in various ethnicities are
      required.

PMID- 19861528
TI  - Impact of not measuring residual gastric volume in mechanically ventilated
      patients receiving early enteral feeding: a prospective before-after study.
AB  - BACKGROUND: Monitoring of residual gastric volume (RGV) to prevent aspiration is
      standard practice in mechanically ventilated patients receiving early enteral
      nutrition (EN). No data are available to support a correlation between RGV and
      adverse event rates. We evaluated whether not measuring RGV affected EN delivery,
      vomiting, or risk of nosocomial pneumonia. METHODS: Two hundred and five eligible
      patients with nasogastric feeding within 48 hours after intubation were included
      in a 7-day prospective before-after study. Continuous 24-hour nutrition was
      started at 25 mL/h then increased by 25 mL/h every 6 hours, to 85 mL/h. In both
      groups, intolerance was treated with erythromycin (250 mg IV/6 h) and a delivery
      rate decrease to the previously well-tolerated rate. RGV monitoring was used
      during the first study period (n = 102), but not during the subsequent
      intervention period (n = 103). Intolerance was defined as RGV >250 mL/6 h or
      vomiting in the standard-practice group and as vomiting in the intervention
      group. RESULTS: Groups were similar for baseline characteristics. Median daily
      volume of enteral feeding was higher in the intervention group (1489;
      interquartile range [IQR], 1349-1647) than in the controls (1381; IQR, 1151-1591;
      P = .002). Intolerance occurred in 47 (46.1%) controls and 27 (26.2%)
      intervention patients (P = .004). The vomiting rate did not differ between
      controls and intervention group patients (24.5% vs 26.2%, respectively; P = .34),
      and neither was a difference found for ventilator-associated pneumonia (19.6% vs
      18.4%; P = .86). CONCLUSION: Early EN without RGV monitoring in mechanically
      ventilated patients improves the delivery of enteral feeding and may not increase
      vomiting or ventilator-associated pneumonia.

PMID- 19861529
TI  - Effect of intravenous omega-3 fatty acids on clinical symptoms of rheumatoid
      arthritis.

PMID- 19861530
TI  - Vitamin D: getting to know you... again.

PMID- 19861531
TI  - Jonathan E. Rhoads lecture: mentoring and nutrition care.

PMID- 19861532
TI  - A.S.P.E.N. recommendations for enteral nutrition: practice is the result of
      potential benefits, harms, clinical judgment, and ethical issues.

PMID- 19861533
TI  - Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive
      use of the histone deacetylase inhibitor LAQ824.
AB  - Tumors grow in the presence of antigen-specific T cells, suggesting the existence
      of intrinsic cancer cell escape mechanisms. We hypothesized that a histone
      deacetylase (HDAC) inhibitor could sensitize tumor cells to immunotherapy because
      this class of agents has been reported to increase tumor antigen expression and
      shift gene expression to a proapoptotic milieu in cancer cells. To test this
      question, we treated B16 murine melanoma with the combination of the HDAC
      inhibitor LAQ824 and the adoptive transfer of gp100 melanoma antigen-specific
      pmel-1 T cells. The combined therapy significantly improved antitumor activity
      through several mechanisms: (a) increase in MHC and tumor-associated antigen
      expression by tumor cells; (b) decrease in competing endogenous lymphocytes in
      recipient mice, resulting in a proliferative advantage for the adoptively
      transferred cells; and (c) improvement in the functional activity of the
      adoptively transferred lymphocytes. We confirmed the beneficial effects of this
      HDAC inhibitor as a sensitizer to immunotherapy in a different model of
      prophylactic prime-boost vaccination with the melanoma antigen tyrosinase-related
      protein 2, which also showed a significant improvement in antitumor activity
      against B16 melanoma. In conclusion, the HDAC inhibitor LAQ824 significantly
      enhances tumor immunotherapy through effects on target tumor cells as well as
      improving the antitumor activity of tumor antigen-specific lymphocytes.

PMID- 19861534
TI  - Noninvasive multiparametric imaging of metastasis-permissive microenvironments in
      a human prostate cancer xenograft.
AB  - Metastasis continues to be one of the major causes of mortality from prostate
      cancer. Because human malignant cell lines metastasize more readily from
      orthotopic sites than from heterotopic sites, to identify metastasis-permissive
      tumor microenvironments, we used noninvasive imaging to compare the in vivo
      vascular, metabolic, and physiologic characteristics of a human prostate cancer
      xenograft implanted orthotopically in the prostate or s.c. in the flank. Hypoxia
      was detected in these xenografts by placing an enhanced green fluorescence
      protein optical reporter under the control of a hypoxia response element. A
      multiparametric analysis of hypoxia, extracellular pH, vascularization, and
      metabolism provided a characterization of environments that are permissive for
      metastasis to occur. We found that orthotopic tumors, which metastasized more
      easily, were characterized by higher vascular volume, permeability, and total
      choline and a more acidic extracellular pH. Interestingly, metastatic deposits in
      the lymph nodes as well as cancer cells in ascites fluid were found to be
      hypoxic, explaining, in part, the refractory nature of metastatic disease. These
      results also provide the basis for clinically translatable noninvasive imaging
      markers for predicting metastatic risk in prostate cancer.

PMID- 19861535
TI  - Fanconi anemia complementation group FANCD2 protein serine 331 phosphorylation is
      important for fanconi anemia pathway function and BRCA2 interaction.
AB  - Fanconi anemia is a cancer-prone inherited bone marrow failure and cancer
      susceptibility syndrome with at least 13 complementation groups (FANCA, FANCB,
      FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, and
      FANCN). Our laboratory has previously described several regulatory
      phosphorylation events for core complex member proteins FANCG and FANCA by
      phosphorylation. In this study, we report a novel phosphorylation site serine 331
      (S331) of FANCD2, the pivotal downstream player of the Fanconi anemia pathway.
      Phosphorylation of S331 is important for its DNA damage-inducible
      monoubiquitylation, resistance to DNA cross-linkers, and in vivo interaction with
      FANCD1/BRCA2. A phosphomimetic mutation at S331 restores all of these phenotypes
      to wild-type. In vitro and in vivo experiments show that phosphorylation of S331
      is mediated by CHK1, the S-phase checkpoint kinase implicated in the Fanconi
      anemia DNA repair pathway.

PMID- 19861536
TI  - p73 and p63 sustain cellular growth by transcriptional activation of cell cycle
      progression genes.
AB  - Despite extensive studies on the role of tumor suppressor p53 protein and its
      homologues, p73 and p63, following their overexpression or cellular stress, very
      little is known about the regulation of the three proteins in cells during
      physiologic cell cycle progression. We report a role for p73 and p63 in
      supporting cellular proliferation through the transcriptional activation of the
      genes involved in G(1)-S and G(2)-M progression. We found that in MCF-7 cells,
      p73 and p63, but not p53, are modulated during the cell cycle with a peak in S
      phase, and their silencing determines a significant suppression of proliferation
      compared with the control. Chromatin immunoprecipitation analysis shows that in
      cycling cells, p73 and p63 are bound to the p53-responsive elements (RE) present
      in the regulatory region of cell cycle progression genes. On the contrary, when
      the cells are arrested in G(0)-G(1), p73 detaches from the REs and it is replaced
      by p53, which represses the expression of these genes. When the cells move in S
      phase, p73 is recruited again and p53 is displaced or is weakly bound to the REs.
      These data open new possibilities for understanding the involvement of p73 and
      p63 in cancer. The elevated concentrations of p73 and p63 found in many cancers
      could cause the aberrant activation of cell growth progression genes and
      therefore contribute to cancer initiation or progression under certain
      conditions.

PMID- 19861537
TI  - Heat shock protein 90 inhibitors: new mode of therapy to overcome endocrine
      resistance.
AB  - Aromatase inhibitors are important drugs to treat estrogen receptor alpha
      (ERalpha)-positive postmenopausal breast cancer patients. However, development of
      resistance to aromatase inhibitors has been observed. We examined whether the
      heat shock protein 90 (HSP90) inhibitor 17-(dimethylaminoethylamino)-17
      demethoxygeldanamycin (17-DMAG) can inhibit the growth of aromatase inhibitor
      resistant breast cancers and the mechanisms by which 17-DMAG affects
      proliferation. Aromatase inhibitor-responsive MCF-7aro and aromatase inhibitor
      resistant LTEDaro breast epithelial cells were used in this study. We observed
      that 17-DMAG inhibited proliferation in both MCF-7aro and LTEDaro cells in a dose
      dependent manner. 17-DMAG induced apoptosis and G(2) cell cycle arrest in both
      cell lines. Although inhibition of HSP90 decreased the levels of ERalpha, the
      ERalpha transcriptional activity was not affected when cells were treated with 17
      DMAG together with estradiol. Moreover, detailed mechanistic studies suggested
      that 17-DMAG inhibits cell growth via degradation of HSP90 client proteins AKT
      and HER2. Collectively, results from this study provide data to support that
      HSP90 inhibitors may be an effective therapy to treat aromatase inhibitor
      resistant breast cancers and that improved efficacy can be achieved by combined
      use of a HSP90 inhibitor and an AKT inhibitor.

PMID- 19861538
TI  - The BRAFV600E oncogene induces transforming growth factor beta secretion leading
      to sodium iodide symporter repression and increased malignancy in thyroid cancer.
AB  - The activating mutation BRAF(V600E) is a frequent genetic event in papillary
      thyroid carcinomas (PTC) that predicts a poor prognosis, leading to loss of
      sodium/iodide symporter (NIS) expression and subsequent radioiodide-refractory
      metastatic disease. The molecular basis of such an aggressive behavior induced by
      BRAF remains unclear. Here, we show a mechanism through which BRAF induces NIS
      repression and promotes epithelial to mesenchimal transition and invasion based
      on the operation of an autocrine transforming growth factor (TGF)beta loop. BRAF
      induces secretion of functional TGFbeta and blocking TGFbeta/Smad signaling at
      multiple levels rescues BRAF-induced NIS repression. Although this mechanism is
      MAP/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK independent,
      secreted TGFbeta cooperates with MEK-ERK signaling in BRAF-induced cell
      migration, Matrigel invasion, and EMT. Consistent with this process, TGFbeta and
      other key components of TGFbeta signaling, such as TbetaRII and pSmad2, are
      overexpressed in human PTC, suggesting a widespread activation of this pathway by
      locally released TGFbeta. Moreover, this high TGFbeta/Smad activity is associated
      with PTC invasion, nodal metastasis, and BRAF status. Interestingly, TGFbeta is
      overexpressed in the invasive front, whereas NIS is preferentially expressed in
      the central regions of the tumors, suggesting that this negative correlation
      between TGFbeta and NIS occurs locally inside the tumor. Our study describes a
      novel mechanism of NIS repression in thyroid cancer and provides evidence that
      TGFbeta may play a key role in promoting radioiodide resistance and tumor
      invasion during PTC progression.

PMID- 19861540
TI  - Tumor growth instability and its implications for chemotherapy.
AB  - Optimal delivery of chemotherapy intensity is dependent on host- and tumor
      specific characteristics. In this article, the chemotherapy late intensity
      schedule is revised to account for tumor growth instability, where a small tumor
      cell fraction emerges that exhibits a higher proliferation rate than the parent
      strain. Modeling this instability as simplified two-population dynamics, we find
      that: (a) if this instability precedes the onset of treatment, the slope of the
      linear increase of the drug concentration for the standard "Norton-Simon late
      intensity schedule" changes and the initial value of the dose strongly depends on
      the ratio of the two tumor cell populations and on their distinct growth rates;
      and (b) if the instability trails the initial treatment, the effective
      chemotherapeutic drug concentration changes as well. Both cases point toward
      testable potential refinements of the Norton-Simon late intensity schedule.

PMID- 19861539
TI  - CXC receptor-1 silencing inhibits androgen-independent prostate cancer.
AB  - The CXC receptor-1 (CXCR1) is a coreceptor for interleukin-8 (IL-8) and is
      expressed on both normal and tumor cells. The function of CXCR1 in prostate
      cancer was investigated by silencing its expression, using RNA interference. We
      established stable cell colonies of PC-3 cells, depleted of CXCR1, using
      lentiviral plasmids (pLK0.1puro) generating small hairpin RNA (shRNA) against
      CXCR1 mRNA. Stable shRNA transfectants (PLK1-PLK5) that express significantly
      reduced CXCR1 mRNA (>or=90% down) and protein (>or=43% down) or vector-only
      transfectants (PC-3V) were characterized. PLK cells showed reduced cell
      proliferation (down, >or=66%), due to cell cycle arrest at G(1)-S phase,
      decreases in Cyclin D1, CDK4, phosphorylated Rb, and extracellular signal
      regulated kinase 1/2 levels compared with those in PC-3V cells. CXCR1 depletion
      lead to increases in spontaneous apoptosis by mitochondria-mediated intrinsic
      mechanism and increases in proapoptotic proteins (BAD, 40%; BAX, 12%), but
      decreases in antiapoptotic proteins (BCL2, down 38%; BCL(xL), 20%). PLK2 cells
      grew as slow-growing tumors (decrease of 54%), compared with that of PC3V tumors
      in athymic mice. Ex vivo analyses of PLK2 tumor tissues showed reduced expression
      of Cyclin D1 and vascular endothelial growth factor, and increased apoptosis
      activity. Other IL-8-expressing prostate cancer cell lines also exhibited similar
      phenotypes when CXCR1 was depleted by CXCR1 shRNA transfection. In contrast to
      these cells, CXCR1 depletion had little effect on IL-8 ligand-deficient LNCaP
      cells. RNA interference rescue using mutated CXCR1 plasmids reversed the
      silencing effect of PLK2, thus demonstrating the specificity of phenotypic
      alteration by CXCR1 shRNA. These studies establish that CXCR1 promotes IL-8
      mediated tumor growth.

PMID- 19861541
TI  - Epigenetic inactivation of the circadian clock gene BMAL1 in hematologic
      malignancies.
AB  - Disruption of circadian rhythms, daily oscillations in biological processes that
      are regulated by an endogenous clock, has been linked to tumorigenesis. Normal
      and malignant tissues often show asynchronies in cell proliferation and metabolic
      rhythms. Cancer chronotherapy takes biological time into account to improve the
      therapy. However, alterations of the circadian clock machinery genes have rarely
      been reported in human cancer. Herein, we show that the BMAL1 gene, a core
      component of the circadian clock, is transcriptionally silenced by promoter CpG
      island hypermethylation in hematologic malignancies, such as diffuse large B-cell
      lymphoma and acute lymphocytic and myeloid leukemias. We also describe how BMAL1
      reintroduction in hypermethylated leukemia/lymphoma cells causes growth
      inhibition in colony assays and nude mice, whereas BMAL1 depletion by RNA
      interference in unmethylated cells enhances tumor growth. We also show that BMAL1
      epigenetic inactivation impairs the characteristic circadian clock expression
      pattern of genes such as C-MYC, catalase, and p300 in association with a loss of
      BMAL1 occupancy in their respective promoters. Furthermore, the DNA
      hypermethylation-associated loss of BMAL1 also prevents the recruitment of its
      natural partner, the CLOCK protein, to their common targets, further enhancing
      the perturbed circadian rhythm of the malignant cells. These findings suggest
      that BMAL1 epigenetic inactivation contributes to the development of hematologic
      malignancies by disrupting the cellular circadian clock.

PMID- 19861542
TI  - Deguelin inhibits growth of breast cancer cells by modulating the expression of
      key members of the Wnt signaling pathway.
AB  - An emphasis in early detection and more effective treatments has decreased the
      mortality rate of breast cancer. Despite this decrease, breast cancer continues
      to be the leading cause of death among women between 40 and 55 years of age and
      is the second overall cause of death among women. Hence, the aim of the present
      study was to assess the therapeutic efficacy of deguelin, a rotenoid isolated
      from several plant species, which has been reported to have chemopreventive
      and/or chemotherapeutic effects in skin, mammary, colon, and lung cancers. The
      effect of deguelin on cell proliferation was evaluated using four human breast
      carcinoma cell lines (MCF-7, BT474, T47D, and MDA-MB-231) by cell count and MTT.
      Moreover, apoptosis was evaluated by acridine/ethidium staining and DNA
      laddering. Gene expression changes following deguelin treatment in MDA-MB-231
      cells was assessed through microarray analysis. Deguelin at 1 mumol/L was found
      to inhibit the growth of the breast cancer cell lines tested with a range of 37%
      to 87%. The highest inhibition was noted for the MDA-MB-231 cell line (MDA-MB
      231>BT474>MCF7>T47D>MCF12F). An arrest at the S phase of the cell cycle and
      apoptosis were shown in the MDA-MB-231 cells treated with deguelin. The
      microarray profile indicated differential expression of two independent pathways,
      including clusters of apoptosis and Wnt/beta-catenin signaling genes in cells as
      a result of deguelin treatment. These studies support the antiproliferative
      effects of deguelin in human breast cancer cells and, perhaps more importantly,
      illustrate novel actions by deguelin in the Wnt signaling pathway.

PMID- 19861543
TI  - Effect of orally administered bovine lactoferrin on the growth of adenomatous
      colorectal polyps in a randomized, placebo-controlled clinical trial.
AB  - Lactoferrin (LF), a secreted, iron binding glycoprotein originally discovered as
      a component of milk, is found in a variety of exocrine secretions and in the
      secondary granules of polymorphonuclear leukocytes. Animal experiments have shown
      that oral administration of bovine lactoferrin (bLF) exerts anticarcinogenesis
      effects in the colon and other organs of the rat. The aim of this study was to
      determine whether oral bLF could inhibit the growth of adenomatous colorectal
      polyps in human patients. A randomized, double-blind, controlled trial was
      conducted in 104 participants, ages 40 to 75 years, with polyps <or=5 mm in
      diameter and likely to be adenomas. Participants were assigned to receive
      placebo, 1.5-g bLF, or 3.0-g bLF daily for 12 months. Target adenomatous polyps
      were monitored by colonoscopy. Ingestion of 3.0-g bLF significantly retarded
      adenomatous polyp growth in participants 63 years old or younger. Removal of
      adenomatous colorectal polyps is done as a preventative measure against
      colorectal cancer; however, polyps can be overlooked, and when detected,
      polypectomy is not always 100% effective in eradicating a polyp. Our study
      suggests that daily intake of 3.0 g of bLF could be a clinically beneficial
      adjunct to colorectal polyp extraction.

PMID- 19861544
TI  - A novel look into estrogen receptor-negative breast cancer prevention with the
      natural, multifunctional signal transduction inhibitor deguelin.
AB  - This perspective on Murillo et al. (beginning on page 942 in this issue of the
      journal) examines the potential of the naturally derived agent deguelin to
      prevent mammary tumorigenesis. These investigators showed that deguelin inhibits
      wnt/beta-catenin signaling in breast cancer cell lines, in addition to inhibiting
      other previously reported signaling pathways. Our growing understanding of
      deguelin mechanisms could lead to important advances in the prevention of
      estrogen receptor-negative breast and other cancers.

PMID- 19861545
TI  - Genetic diagnosis by whole exome capture and massively parallel DNA sequencing.
AB  - Protein coding genes constitute only approximately 1% of the human genome but
      harbor 85% of the mutations with large effects on disease-related traits.
      Therefore, efficient strategies for selectively sequencing complete coding
      regions (i.e., "whole exome") have the potential to contribute to the
      understanding of rare and common human diseases. Here we report a method for
      whole-exome sequencing coupling Roche/NimbleGen whole exome arrays to the
      Illumina DNA sequencing platform. We demonstrate the ability to capture
      approximately 95% of the targeted coding sequences with high sensitivity and
      specificity for detection of homozygous and heterozygous variants. We illustrate
      the utility of this approach by making an unanticipated genetic diagnosis of
      congenital chloride diarrhea in a patient referred with a suspected diagnosis of
      Bartter syndrome, a renal salt-wasting disease. The molecular diagnosis was based
      on the finding of a homozygous missense D652N mutation at a position in SLC26A3
      (the known congenital chloride diarrhea locus) that is virtually completely
      conserved in orthologues and paralogues from invertebrates to humans, and
      clinical follow-up confirmed the diagnosis. To our knowledge, whole-exome (or
      genome) sequencing has not previously been used to make a genetic diagnosis. Five
      additional patients suspected to have Bartter syndrome but who did not have
      mutations in known genes for this disease had homozygous deleterious mutations in
      SLC26A3. These results demonstrate the clinical utility of whole-exome sequencing
      and have implications for disease gene discovery and clinical diagnosis.

PMID- 19861546
TI  - Networks of spatial genetic variation across species.
AB  - Spatial patterns of genetic variation provide information central to many
      ecological, evolutionary, and conservation questions. This spatial variability
      has traditionally been analyzed through summary statistics between pairs of
      populations, therefore missing the simultaneous influence of all populations.
      More recently, a network approach has been advocated to overcome these
      limitations. This network approach has been applied to a few cases limited to a
      single species at a time. The question remains whether similar patterns of
      spatial genetic variation and similar functional roles for specific patches are
      obtained for different species. Here we study the networks of genetic variation
      of four Mediterranean woody plant species inhabiting the same habitat patches in
      a highly fragmented forest mosaic in Southern Spain. Three of the four species
      show a similar pattern of genetic variation with well-defined modules or groups
      of patches holding genetically similar populations. These modules can be thought
      of as the long-sought-after, evolutionarily significant units or management
      units. The importance of each patch for the cohesion of the entire network,
      though, is quite different across species. This variation creates a tremendous
      challenge for the prioritization of patches to conserve the genetic variation of
      multispecies assemblages.

PMID- 19861547
TI  - Structure of the lethal phage pinhole.
AB  - Perhaps the simplest of biological timing systems, bacteriophage holins
      accumulate during the phage morphogenesis period and then trigger to permeabilize
      the cytoplasmic membrane with lethal holes; thus, terminating the infection
      cycle. Canonical holins form very large holes that allow nonspecific release of
      fully-folded proteins, but a recently discovered class of holins, the pinholins,
      make much smaller holes, or pinholes, that serve only to depolarize the membrane.
      Here, we interrogate the structure of the prototype pinholin by negative-stain
      transmission electron-microscopy, cysteine-accessibility, and chemical cross
      linking, as well as by computational approaches. Together, the results suggest
      that the pinholin forms symmetric heptameric structures with the hydrophilic
      surface of one transmembrane domain lining the surface of a central channel
      approximately 15 A in diameter. The structural model also suggests a rationale
      for the prehole state of the pinholin, the persistence of which defines the
      duration of the viral latent period, and for the sensitivity of the holin timing
      system to the energized state of the membrane.

PMID- 19861548
TI  - TRPM1 is required for the depolarizing light response in retinal ON-bipolar
      cells.
AB  - The ON pathway of the visual system, which detects increases in light intensity,
      is established at the first retinal synapse between photoreceptors and ON-bipolar
      cells. Photoreceptors hyperpolarize in response to light and reduce the rate of
      glutamate release, which in turn causes the depolarization of ON-bipolar cells.
      This ON-bipolar cell response is mediated by the metabotropic glutamate receptor,
      mGluR6, which controls the activity of a depolarizing current. Despite intensive
      research over the past two decades, the molecular identity of the channel that
      generates this depolarizing current has remained elusive. Here, we present
      evidence indicating that TRPM1 is necessary for the depolarizing light response
      of ON-bipolar cells, and further that TRPM1 is a component of the channel that
      generates this light response. Gene expression profiling revealed that TRPM1 is
      highly enriched in ON-bipolar cells. In situ hybridization experiments confirmed
      that TRPM1 mRNA is found in cells of the retinal inner nuclear layer, and
      immunofluorescent confocal microscopy showed that TRPM1 is localized in the
      dendrites of ON-bipolar cells in both mouse and macaque retina. The
      electroretinogram (ERG) of TRPM1-deficient (TRPM1(-/-)) mice had a normal a-wave,
      but no b-wave, indicating a loss of bipolar cell response. Finally, whole-cell
      patch-clamp recording from ON-bipolar cells in mouse retinal slices demonstrated
      that genetic deletion of TRPM1 abolished chemically simulated light responses
      from rod bipolar cells and dramatically altered the responses of cone ON-bipolar
      cells. Identification of TRPM1 as a mGluR6-coupled cation channel reveals a key
      step in vision, expands the role of the TRP channel family in sensory perception,
      and presents insights into the evolution of vertebrate vision.

PMID- 19861549
TI  - Imaging the interaction of HIV-1 genomes and Gag during assembly of individual
      viral particles.
AB  - The incorporation of viral genomes into particles has never previously been
      imaged in live infected cells. Thus, for many viruses it is unknown how the
      recruitment and packaging of genomes into virions is temporally and spatially
      related to particle assembly. Here, we devised approaches to simultaneously image
      HIV-1 genomes, as well as the major HIV-1 structural protein, Gag, to reveal
      their dynamics and functional interactions during the assembly of individual
      viral particles. In the absence of Gag, HIV-1 RNA was highly dynamic, moving in
      and out of the proximity of the plasma membrane. Conversely, in the presence of
      Gag, RNA molecules docked at the membrane where their lateral movement slowed and
      then ceased as Gag assembled around them and they became irreversibly anchored.
      Viral genomes were not retained at the membrane when their packaging signals were
      mutated, nor when expressed with a Gag mutant that was not myristoylated. In the
      presence of a Gag mutant that retained membrane- and RNA-binding activities but
      could not assemble into particles, the viral RNA docked at the membrane but
      continued to drift laterally and then often dissociated from the membrane. These
      results, which provide visualization of the recruitment and packaging of genomes
      into individual virus particles, demonstrate that a small number of Gag molecules
      recruit viral genomes to the plasma membrane where they nucleate the assembly of
      complete virions.

PMID- 19861551
TI  - On the evaporation of ammonium sulfate solution.
AB  - Aqueous evaporation and condensation kinetics are poorly understood, and
      uncertainties in their rates affect predictions of cloud behavior and therefore
      climate. We measured the cooling rate of 3 M ammonium sulfate droplets undergoing
      free evaporation via Raman thermometry. Analysis of the measurements yields a
      value of 0.58 +/- 0.05 for the evaporation coefficient, identical to that
      previously determined for pure water. These results imply that subsaturated
      aqueous ammonium sulfate, which is the most abundant inorganic component of
      atmospheric aerosol, does not affect the vapor-liquid exchange mechanism for
      cloud droplets, despite reducing the saturation vapor pressure of water
      significantly.

PMID- 19861552
TI  - Evolutionary history and species interactions.

PMID- 19861550
TI  - The immune response attenuates growth and nutrient storage in Drosophila by
      reducing insulin signaling.
AB  - Innate immunity is the primary and most ancient defense against infection.
      Although critical to survival, coordinating protection against a foreign organism
      is energetically costly, creating the need to reallocate substrates from
      nonessential functions, such as growth and nutrient storage. However, the
      mechanism by which infection or inflammation leads to a reduction in energy
      utilization by these dispensable processes is not well understood. Here, we
      demonstrate that activation of the Toll signaling pathway selectively in the fat
      body, the major immune and lipid storage organ of the fruit fly, Drosophila
      melanogaster, leads to both induction of immunity and reallocation of resources.
      Toll signaling in the fat body suppresses insulin signaling both within these
      cells and non-autonomously throughout the organism, leading to a decrease in both
      nutrient stores and growth. These data suggest that communication between these
      two regulatory systems evolved as a means to divert energy in times of need from
      organismal growth to the acute requirement of combating infection.

PMID- 19861553
TI  - Loss of an exosome complex component potentiates R gene-independent cell death in
      barley.

PMID- 19861554
TI  - The ferroportin metal efflux proteins function in iron and cobalt homeostasis in
      Arabidopsis.
AB  - Relatively little is known about how metals such as iron are effluxed from cells,
      a necessary step for transport from the root to the shoot. Ferroportin (FPN) is
      the sole iron efflux transporter identified to date in animals, and there are two
      closely related orthologs in Arabidopsis thaliana, IRON REGULATED1 (IREG1/FPN1)
      and IREG2/FPN2. FPN1 localizes to the plasma membrane and is expressed in the
      stele, suggesting a role in vascular loading; FPN2 localizes to the vacuole and
      is expressed in the two outermost layers of the root in response to iron
      deficiency, suggesting a role in buffering metal influx. Consistent with these
      roles, fpn2 has a diminished iron deficiency response, whereas fpn1 fpn2 has an
      elevated iron deficiency response. Ferroportins also play a role in cobalt
      homeostasis; a survey of Arabidopsis accessions for ionomic phenotypes showed
      that truncation of FPN2 results in elevated shoot cobalt levels and leads to
      increased sensitivity to the metal. Conversely, loss of FPN1 abolishes shoot
      cobalt accumulation, even in the cobalt accumulating mutant frd3. Consequently,
      in the fpn1 fpn2 double mutant, cobalt cannot move to the shoot via FPN1 and is
      not sequestered in the root vacuoles via FPN2; instead, cobalt likely accumulates
      in the root cytoplasm causing fpn1 fpn2 to be even more sensitive to cobalt than
      fpn2 mutants.

PMID- 19861555
TI  - Exocytosis precedes and predicts the increase in growth in oscillating pollen
      tubes.
AB  - We examined exocytosis during oscillatory growth in lily (Lilium formosanum and
      Lilium longiflorum) and tobacco (Nicotiana tabacum) pollen tubes using three
      markers: (1) changes in cell wall thickness by Nomarski differential interference
      contrast (DIC), (2) changes in apical cell wall fluorescence in cells stained
      with propidium iodide (PI), and (3) changes in apical wall fluorescence in cells
      expressing tobacco pectin methyl esterase fused to green fluorescent protein (PME
      GFP). Using PI fluorescence, we quantified oscillatory changes in the amount of
      wall material from both lily and tobacco pollen tubes. Measurement of wall
      thickness by DIC was only possible with lily due to limitations of microscope
      resolution. PME-GFP, a direct marker for exocytosis, only provides information in
      tobacco because its expression in lily causes growth inhibition and cell death.
      We show that exocytosis in pollen tubes oscillates and leads the increase in
      growth rate; the mean phase difference between exocytosis and growth is -98
      degrees +/- 3 degrees in lily and -124 degrees +/- 4 degrees in tobacco.
      Statistical analyses reveal that the anticipatory increase in wall material
      predicts, to a high degree, the rate and extent of the subsequent growth surge.
      Exocytosis emerges as a prime candidate for the initiation and regulation of
      oscillatory pollen tube growth.

PMID- 19861556
TI  - Transcript-based cloning of RRP46, a regulator of rRNA processing and R gene
      independent cell death in barley-powdery mildew interactions.
AB  - Programmed cell death (PCD) plays a pivotal role in plant development and
      defense. To investigate the interaction between PCD and R gene-mediated defense,
      we used the 22K Barley1 GeneChip to compare and contrast time-course expression
      profiles of Blumeria graminis f. sp hordei (Bgh) challenged barley (Hordeum
      vulgare) cultivar C.I. 16151 (harboring the Mla6 powdery mildew resistance
      allele) and its fast neutron-derived Bgh-induced tip cell death1 mutant, bcd1.
      Mixed linear model analysis identified genes associated with the cell death
      phenotype as opposed to R gene-mediated resistance. One-hundred fifty genes were
      found at the threshold P value < 0.0001 and a false discovery rate <0.6%. Of
      these, 124 were constitutively overexpressed in the bcd1 mutant. Gene Ontology
      and rice (Oryza sativa) alignment-based annotation indicated that 68 of the 124
      overexpressed genes encode ribosomal proteins. A deletion harboring six genes on
      chromosome 5H cosegregates with bcd1-specified cell death and is associated with
      misprocessing of rRNAs but segregates independent of R gene-mediated resistance.
      Barley stripe mosaic virus-induced gene silencing of one of the six deleted
      genes, RRP46 (rRNA-processing protein 46), phenocopied bcd1-mediated tip cell
      death. These findings suggest that RRP46, a critical component of the exosome
      core, mediates RNA processing and degradation involved in cell death initiation
      as a result of attempted penetration by Bgh during the barley-powdery mildew
      interaction but is independent of gene-for-gene resistance.

PMID- 19861557
TI  - EGFR fluorescence in situ hybridisation assay: guidelines for application to non
      small-cell lung cancer.
AB  - There is a need for predictive biomarkers that identify non-small-cell lung
      cancer (NSCLC) patients most likely to respond to epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There are numerous
      potential candidates, although none has been proven in prospective clinical
      trials. The EGFR gene copy number evaluated by fluorescence in situ hybridisation
      (FISH) has been highlighted as one of the most effective markers for sensitivity
      to EGFR TKIs in large phase III, randomised placebo-controlled trials and has
      been used in clinical settings to assist physicians in defining the therapeutic
      regimen. The EGFR FISH assay has technical challenges and it is critical that
      detailed guidelines are provided to help clinical laboratories in performing and
      interpreting the test. Excellent assay reproducibility and portability rates
      among laboratories are crucial to guarantee that accurate clinical decisions can
      be made for patients with NSCLC. This article discusses the consensus outcomes of
      a global workshop convened to discuss key technical issues and standardise
      reading strategies for the EGFR FISH assay of NSCLC tumour tissue.

PMID- 19861558
TI  - The clinicopathological significance of BUBR1 overexpression in hepatocellular
      carcinoma.
AB  - BACKGROUND AND AIMS: BUBR1 is a key component of the mitotic spindle checkpoint,
      and its roles in human cancers are controversial and unclear. The aim of this
      study was to investigate the clinicopathological significance of BUBR1 expression
      in hepatocellular carcinoma (HCC). METHODS: The BUBR1 protein and its mRNA levels
      were measured in 58 HCCs, nine high-grade dysplastic nodules and their paired non
      tumorous liver tissues by quantitative real-time polymerase chain reaction (qPCR)
      and western blot, respectively. In addition, immunochemical analysis of the BUBR1
      protein was performed in 458 HCCs and 46 dysplastic nodules, and the
      clinicopathological significance of the BUBR1 expression was evaluated. RESULTS:
      The BUBR1 expression at both mRNA and protein levels was elevated in two of nine
      high-grade dysplastic nodules and in 37 of 58 (64%) HCCs. BUBR1 was overexpressed
      in 207 of 458 (45%) HCCs by immunohistochemistry. Intriguingly, high expression
      of the BUBR1 was correlated with larger tumour size, higher histological grade,
      advanced pathological stage, and poor overall and recurrence-free survival. There
      was a higher frequency of BUBR1 overexpression in cases with positive serum HBsAg
      than those with negative HBsAg. Moreover, BUBR1 overexpression was associated
      with P53 staining and high Ki67 labelling indices in HCC tissues. CONCLUSIONS:
      BUBR1 was overexpressed in about 45% HCCs, and its overexpression may be a
      relative lately event in HCC progression. Overexpression of BUBR1 was associated
      with worse prognosis and is a potential prognostic factor for patients with HCC.

PMID- 19861559
TI  - The significance of tumour cell immunophenotype in myeloma and its impact on
      clinical outcome.
AB  - BACKGROUND AND AIMS: Antigen expression of multiple myeloma (MM) cells is
      heterogeneous. We have investigated the clinical impact of expression of some of
      the commonly used immunohistochemical markers in the diagnostic work-up of bone
      marrow trephine biopsy (BMTB) samples in MM. PATIENTS AND METHODS: BMTB samples
      from 107 MM patients who had received an autologous stem cell transplant (ASCT)
      following chemotherapy were evaluated. In 75 cases, the immunophenotype had been
      evaluated on two or more occasions on further follow-up. RESULTS: In the cases
      evaluated, 32%, 79%, 73%, 39% and 60% of cases had been scored positive for CD20,
      CD79a, CD56, cyclin D1 and epithelial membrane antigen (EMA) respectively.
      Absence of CD79a was predictive of poor overall survival (OS) from the time of
      transplant (p = 0.029) and poor event-free survival (EFS) from the time of
      transplant (p = 0.003). Absence of EMA (p = 0.02) was predictive of poor EFS from
      the time of diagnosis. Presence of CD56 was predictive of poor EFS from the time
      of diagnosis (p = 0.026). On multivariate analysis, only CD79a expression (OS and
      EFS from the time of transplant) and EMA expression (EFS from the time of
      diagnosis) maintained their significance. 13 of 75 patients showed an
      immunophenotypic drift during the disease course. Loss of CD20 (four cases)
      during the disease course in cases that were previously scored positive
      correlated with significant worsening both, of OS (p = 0.02) and EFS (p = 0.009)
      from the time of diagnosis. CONCLUSION: Immunophenotype impacts on clinical
      outcome in MM.

PMID- 19861560
TI  - Proteins from the Wnt pathway are involved in the pathogenesis and progression of
      mammary phyllodes tumours.
AB  - BACKGROUND: The Wnt pathway is important in cell signalling transduction and is
      involved in the pathogenesis of multiple tumour types. A comprehensive analysis
      of the expression of Wnt signalling pathway proteins in mammary phyllodes tumours
      (PTs) has not been previously performed. AIMS: To evaluate the
      immunohistochemical expression of Wnt pathway proteins in a cohort of PTs, to
      determine their role in tumour pathogenesis and to identify any associations with
      patient outcome. METHODS: 65 PTs (34 benign, 23 borderline and 8 malignant)
      diagnosed at a single institution between 1990 and 2006 were analysed.
      Immunohistochemical stains were performed on tissue microarrays for beta-catenin,
      Wnt1, Wnt5a, SFRP4 and E-cadherin. Stroma and epithelium were scored separately.
      RESULTS: Stromal cytoplasmic Wnt5a and SFRP4 expression showed significant
      progressive increases in expression with increasing grade (p = 0.002 and p = 0.02
      respectively). Epithelial membranous and stromal nuclear beta-catenin, epithelial
      cytoplasmic Wnt1 and epithelial E-cadherin all also showed increasing expression
      with increasing tumour grade, however, the differences were not significant.
      Disease-free survival was significantly decreased (p = 0.0017) with positive
      epithelial E-cadherin staining. CONCLUSIONS: Results suggest that alterations in
      the Wnt pathway are important in the progression and in the epithelial and
      stromal interactions in PTs. They have important implications for understanding
      the pathogenesis of these uncommon but clinically important tumours.

PMID- 19861561
TI  - Use of an elastic stain to show venous invasion in colorectal carcinoma: a simple
      technique for detection of an important prognostic factor.
AB  - BACKGROUND: Venous invasion (VI) is an important prognostic factor in colorectal
      cancer; it is positively associated with visceral metastases and may affect the
      decision to treat with adjuvant therapy. AIMS: To evaluate whether an elastic
      tissue (Movat) stain facilitates identification of VI, the number of Movat
      stained blocks needed to detect VI, and whether VI identified with a Movat stain
      is prognostically equivalent to VI identified on H&E-stained slides. METHODS: H&E
      stained sections from colorectal carcinomas from the year 2000 (n = 92) were
      examined for VI and compared to Movat-stained slides. Clinical charts were
      reviewed to compare rates of metastases in VI-positive versus VI-negative
      patients. RESULTS: With the Movat stain, VI was identified in 44% of cases
      previously categorised as negative (p<0.001) on review of H&E slides alone. One
      Movat-stained section was often sufficient to identify VI, with a statistically
      significant benefit to performing multiple stains if necessary. In H&E sections,
      two clues helped identify VI: the "unaccompanied artery" sign, where large
      arteries were seen without an accompanying vein; and the "protruding tongue"
      sign, where smooth tongues of tumour extended into pericolic/rectal fat.
      Metastases were present in 61% of cases positive for VI compared to 35% in VI
      negative cases (p = 0.03). 45% of cases positive for intramural VI only developed
      metastases (p = 0.39), while 65% of cases positive for extramural VI only
      developed metastases (p = 0.03). CONCLUSIONS: Pathologists should look for
      morphological clues of VI in H&E stained sections; when VI is not apparent, an
      elastic tissue stain on all tumour blocks significantly improves identification
      of VI. Morphological clues include the "unaccompanied artery" and "protruding
      tongue" signs.

PMID- 19861562
TI  - An autopsy report on multiple system atrophy diagnosed immunohistochemically
      despite severe ischaemic damage: a new approach for investigation of medical
      practice associated deaths in Japan.
AB  - A 60-year old man with a 10-year history of multiple system atrophy (MSA) was
      found in respiratory arrest. After 4 months of respiratory support with two
      episodes of septic shock, he died. Autopsy disclosed severe atrophy of the
      mesencephalon, brainstem, medulla oblongata and cerebellum. Gallyas-Braak, alpha
      synuclein and ubiquitin-positive inclusions in the cytoplasm of glial cells were
      evident, despite the severe ischaemic damage due to respiratory arrest and
      subsequent respiratory support for 4 months. The cause of respiratory arrest was
      not identified, but could be explained by the natural history of MSA. The
      bereaved family, who had suspected malpractice, was satisfied with the
      explanation based on the investigation performed by eight expert doctors, one
      expert nurse, two coordinator nurses and two lawyers in the model project
      promoted by the Japanese government.

PMID- 19861563
TI  - Mucosal prolapse syndrome presenting as rectal polyposis.
AB  - Mucosal prolapse syndrome comprises a variety of clinical and histopathological
      entities, with mucosal prolapse as the underlying pathogenic mechanism. Due to
      variable clinical, endoscopic and histopathological presentation and rareness of
      symptomatic mucosal prolapse, misdiagnosis resulting in delayed or inappropriate
      treatment is frequent. This report describes a patient initially diagnosed with a
      colorectal polyposis syndrome consisting of multiple rectal hyperplastic and
      adenomatous polyps. But after careful review of medical history and
      histopathology, the patient was found to have a rare variant of solitary rectal
      ulcer syndrome presenting as rectal polyposis. The recognition of rectal
      polyposis as a manifestation of solitary rectal ulcer syndrome/mucosal prolapse
      syndrome will improve diagnosis and treatment and prevent inappropriate
      management of this condition.

PMID- 19861564
TI  - Primary myxoid liposarcoma of the thyroid gland.
AB  - Primary myxoid liposarcoma of the thyroid gland is extremely rare. This report
      describes such a case. A 59-year-old woman was admitted for evaluation of a 6 x 6
      x 5 cm nodule in the left lobe of the thyroid gland. Left thyroid lobectomy was
      performed without any postoperative treatment except for follow-up. Osseous and
      pulmonary metastasis developed 1 year later and the patient died 15 months after
      the surgery. The clinical course and treatment choice are discussed.

PMID- 19861565
TI  - Titrimetric immunohistochemical evaluation of DNA hypomethylation in uterine
      tumours.
AB  - BACKGROUND: Global DNA hypomethylation is a well established feature of many
      common cancers. AIMS: To establish a simple semi-quantitative, titrimetric
      immunohistochemical method in order to exploit this trait for prognostic
      purposes, in uterine cancers. METHODS: A monoclonal antibody against 5
      methylcytidine was used for immunohistochemical staining of methylated DNA in
      tumour cells. The degree of methylated DNA in the tumour tissue was visually
      compared and matched to that of normal tissues stained by serial decreasing
      concentrations of antibody to 5-methylcytidine. RESULTS: Using this method a
      significant correlation was found between the histological stage and the
      reduction in DNA methylation in uterine adenocarcinoma (n = 39) and uterine
      squamous cell carcinoma (n = 23). CONCLUSIONS: A simple titrimetric
      immunohistochemical method has been developed for quantitative evaluation of
      ligands. This method should be further employed in follow-up studies, in order to
      establish the prognostic value of DNA hypomethylation in uterine cancer.

PMID- 19861566
TI  - Detection of PCR products using self-reporting duplex mutation primers.
AB  - A novel oligonucleotide probe, with duplex mutation primers, which comprised a
      normal reverse primer labelled with a fluorophore at its 5'-end and a single-base
      mismatched complementary oligonucleotide labelled with a quencher at its 3'-end,
      was designed. Its application in the detection of hepatitis B virus (HBV) DNA of
      serum was investigated; results were compared with those obtained using a
      commercial TaqMan kit. There was a good linear correlation in the range of 10(2)
      approximately 10(7) copies/ml (r(2) = 0.999) with the method. Intra-experimental
      coefficients of variation (CVs) were 0.70% approximately 7.80%, and inter
      experimental CVs were 0.78% approximately 9.02%, respectively. There was no
      significant difference of HBV genome number tested by the two methods (p<0.05) in
      132 hepatitis B patients; HBV DNA was not detected in any serum samples of 20
      healthy volunteers by the two methods.

PMID- 19861568
TI  - Sensitivity and specificity in diagnostic accuracy: ROC solid or lost in
      translation?

PMID- 19861569
TI  - Receiver-operating characteristic curve analysis in diagnostic, prognostic and
      predictive biomarker research: trade-off between sensitivity and specificity with
      change of test cut-offs.

PMID- 19861570
TI  - To study the effect of the sequence of seven pranayama by Swami Ramdev on gene
      expression in leukaemia patients and rapid interpretation of gene expression.

PMID- 19861571
TI  - Revised national guidelines for the analysis of cerebrospinal fluid for bilirubin
      in suspected subarachnoid haemorrhage: interpret with caution.

PMID- 19861572
TI  - Adult hepatic epitheloid haemangioendothelioma presenting with Kasabach-Merrit
      syndrome: a case report.

PMID- 19861574
TI  - Differential pharmacodynamic effects of paclitaxel formulations in an
      intracranial rat brain tumor model.
AB  - Nano- and microparticulate carriers can exert a beneficial impact on the
      pharmacodynamics of anticancer agents. To investigate the relationships between
      carrier and antitumor pharmacodynamics, paclitaxel incorporated in liposomes (L
      pac) was compared with the clinical standard formulated in Cremophor-EL/ethanol
      (Cre-pac) in a rat model of advanced primary brain cancer. Three maximum
      tolerated-dose regimens given by intravenous administration were investigated: 50
      mg/kg on day 8 (d8) after implantation of 9L gliosarcoma tumors; 40 mg/kg on d8
      and d15; 20 mg/kg on d8, d11, and d15. Body weight change and neutropenia were
      assessed as pharmacodynamic markers of toxicity. The pharmacodynamic markers of
      antitumor efficacy were increase in lifespan (ILS) and tumor volume progression,
      measured noninvasively by magnetic resonance imaging. At equivalent doses,
      neutropenia was similar for both formulations, but weight loss was more severe
      for Cre-pac. No regimen of Cre-pac extended survival, whereas L-pac at 40 mg/kg
      x2 doses was well tolerated and mediated 26% ILS (p < 0.0002) compared with
      controls. L-pac at a lower cumulative dose (20 mg/kg x3) was even more effective
      (40% ILS; p < 0.0001). In striking contrast, the identical regimen of Cre-pac was
      lethal. Development of a novel semimechanistic pharmacodynamic model permitted
      quantitative hypothesis testing with the tumor volume progression data, and
      suggested the existence of a transient treatment effect that was consistent with
      sensitization or "priming" of tumors by more frequent L-pac dosing schedules.
      Therefore, improved antitumor responses of carrier-based paclitaxel formulations
      can arise both from dose escalation, because of reduced toxicity, and from novel
      carrier-mediated alterations of antitumor pharmacodynamic effects.

PMID- 19861575
TI  - Incidence and risk factors for central nervous system relapse in patients with
      diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP
      chemotherapy.
AB  - BACKGROUND: The addition of rituximab to CHOP (R-CHOP; CHOP, cyclophosphamide,
      doxorubicin, vincristine, and prednisone) chemotherapy improves outcome in
      patients with diffuse large B-cell lymphoma (DLBCL). We evaluated the risk of
      central nervous system (CNS) relapse in the R-CHOP in a population-based cohort
      of patients with DLBCL. METHODS: Patients with DLBCL diagnosed from 1 September
      1999 to 14 January 2005 at the British Columbia Cancer Agency (BCCA) were
      identified. Patients were included if they were > or =16 years old with advanced
      stage or any stage with testicular involvement and were treated with CHOP (1999
      2001) or R-CHOP (2001-2005) with curative intent. RESULTS: Four hundred and
      thirty-five patients were identified; 126 (29%) were treated with CHOP and 309
      (71%) with R-CHOP. With a median follow-up of 5.7 years, there were 31 CNS
      relapses in total with a trend to a reduced likelihood of CNS relapse in R-CHOP
      treated patients (3-year risk 9.7% versus 6.4, P = 0.085). In multivariate
      analysis, the use of rituximab significantly reduced the risk of CNS relapse
      [hazard ratio (HR) 0.45, P = 0.034]; this benefit was more striking in patients
      who achieved a complete response (HR 0.18, P = 0.005). CONCLUSION: The use of R
      CHOP appears to reduce the overall risk of CNS relapse in patients with DLBCL
      particularly in patients who achieve a complete response.

PMID- 19861576
TI  - Aromatase inhibition in male breast cancer patients: biological and clinical
      implications.
AB  - BACKGROUND: The role of aromatase inhibitors (AIs) and their impact on estradiol
      (E(2)) levels remain unknown in male breast cancer (MBC) patients. PATIENTS AND
      METHODS: MBC patients with metastatic disease and those treated with AIs were
      selected from the breast cancer database of the Centre Antoine-Lacassagne (Nice,
      France). Sex hormone levels were retrospectively assessed on serum samples from
      our institutional serum bank. RESULTS: Fifteen patients entered the study. Two
      patients (13%) had complete response, four patients (27%) had partial response,
      two patients (13%) had stable disease and seven patients (47%) had progressive
      disease. The median progression-free survival and overall survival were 4.4
      months [95% confidence interval (CI) 0.1-8.6] and 33 months (95% CI 18.4-47.6),
      respectively. All assessable patients (n = 6) had E(2) levels less than the lower
      limit of the assay during AI treatment. Among them, three had partial response,
      one had stable disease and two had progressive disease. A large increase in
      follicle-stimulating hormone, luteinizing hormone and E(2) levels was observed in
      one responding patient at progression. CONCLUSIONS: AIs are active in MBC
      patients. This activity is correlated with a significant reduction in E(2)
      levels. Secondary resistance is in part related to a deleterious feedback loop
      resulting in a significant increase in substrate for aromatization.

PMID- 19861577
TI  - Circulating tumour cells early predict progression-free and overall survival in
      advanced colorectal cancer patients treated with chemotherapy and targeted
      agents.
AB  - BACKGROUND: Early predictive markers for response are needed for advanced
      colorectal cancer (ACC) patients. We assessed the value of circulating tumour
      cells (CTC) in ACC patients treated with chemotherapy plus targeted agents
      (CAIRO2 phase III trial) and compared the results with computed tomography (CT)
      imaging. MATERIALS AND METHODS: CTC were determined at baseline and at different
      time points during treatment. Patients were stratified into low (less than three
      CTC per 7.5 ml of blood) or high CTC (three or more CTC per 7.5 ml of blood).
      RESULTS: A total of 467 patients were assessable for CTC analysis. Among them,
      129 patients (29%) with high baseline CTC had a significantly decreased
      progression-free survival [PFS; hazard ratio (HR) 1.5] and overall survival (OS;
      HR 2.2) compared with 322 patients with low baseline CTC. This difference
      remained statistically significant during treatment. The sensitivity and
      specificity of high CTC at baseline for the prediction of progressive disease on
      CT imaging were 16.7% and 70.1%, respectively, and of high CTC at 1-2 weeks after
      the start of treatment 20.0% and 95.1%, respectively. The combined analysis of
      CTC and CT imaging provided a more accurate outcome assessment than either
      modality alone. CONCLUSIONS: The CTC count before and during treatment
      independently predicts PFS and OS in ACC patients treated with chemotherapy plus
      targeted agents and provides additional information to CT imaging.

PMID- 19861578
TI  - MACOP-B regimen in the treatment of adult Langerhans cell histiocytosis:
      experience on seven patients.
AB  - BACKGROUND: Adult Langerhans cell histiocytosis (LCH) is a rare disease. The
      combination of vinblastine and prednisone, given in a 6-month course, is the
      standard of care but prospective randomized trials are lacking. PATIENTS AND
      METHODS: We report our monocentric experience in the treatment of seven adult
      patients with multisystem (MS) LCH (n = 3) or single-system multifocal (SS-m) LCH
      (n = 4) with the short-course intensive chemotherapy regimen methotrexate,
      doxorubicin, cyclophosphamide, vincristine, prednisone and bleomicin (MACOP-B).
      RESULTS: The overall response rate was 100% [five complete response (CR), two
      partial response (PR)]. After a median follow-up of 6.5 years, four patients are
      in first continuous CR and three patients relapsed after 5, 8 and 62 months,
      respectively. Four patients were evaluated with positron emission tomography
      (PET) scan: all three PET-negative patients at the end of treatment had a long
      lasting response with only one patient relapsing after 5 years. PET scan detected
      additional bone lesions at diagnosis in two of four patients, changing the
      treatment program in one of them. CONCLUSIONS: MACOP-B regimen seems to be very
      active in the treatment of adult MS or SS-m LCH, with long-lasting responses in
      five of seven patients. PET scan merits further evaluation in the initial staging
      and in the evaluation of the response to chemotherapy.

PMID- 19861579
TI  - Outcomes after repeated resection for recurrent pulmonary metastases from
      colorectal cancer.
AB  - BACKGROUND: It remains controversial whether metastasectomy is still feasible in
      patients with pulmonary recurrence from colorectal cancer, after initial
      metastasectomy. The aim of this study was to evaluate outcomes of repeated
      metastasectomy in these patients. MATERIALS AND METHODS: From 1995 to 2007, 202
      patients had received a pulmonary metastasectomy from colorectal cancer at our
      institution. Over a median follow-up of 28.9 months, 48 patients received second
      metastasectomy (29 wedge resections, 5 segmentectomies, 13 lobectomies, and 1
      completion pneumonectomy). The median disease-free interval was 9.6 months. Among
      these 48 patients, 28 showed pulmonary recurrence again and of those, 10 patients
      received third metastasectomy (two wedge resections, two segmentectomies, four
      lobectomies, and two completion pneumonectomies). RESULTS: There was no
      postoperative mortality. Of the 48 patients who underwent second metastasectomy,
      overall and disease-free 5-year survivals were 79% and 49%, respectively, after
      second operation. Of the 10 patients who received third metastasectomy, overall
      survival was 78% at 5 years after last operation. CONCLUSIONS: Repeated resection
      after initial metastasectomy can be carried out safely and provides long-term
      survival in patients with recurrent pulmonary metastasis from colorectal cancer.
      Our findings indicate that close follow-up for the early detection of recurrence
      and parenchyma-saving resection can improve the results after repeated resection.

PMID- 19861580
TI  - The impact of carcinoembryonic antigen flare in patients with advanced colorectal
      cancer receiving first-line chemotherapy.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) flare may have a favourable response
      to chemotherapy, but its impact on survival is unknown. This study aimed to
      evaluate the incidence of CEA flare and its impact on objective response rate
      (ORR), progression-free survival (PFS) and overall survival (OS). PATIENTS AND
      METHODS: Patients with histologically proven advanced colorectal cancer
      undergoing first-line chemotherapy with three or more serial CEA measurements
      (one at baseline and two or more during treatment) were included. Patients were
      grouped according to CEA kinetic as flare (F), decreasing CEA, normal baseline
      CEA, stable CEA and increasing CEA (I). RESULTS: From January 2000 to February
      2008, 837 patients were screened of whom 670 were eligible. CEA flare occurred in
      78 (11.6%) patients. On multivariate analysis, compared with patients with
      increasing CEA, patients with CEA flare had a significantly better ORR [I versus
      F: 11% versus 73%; risk ratio (RR): 27.96; 95% confidence interval (CI): 9.55
      81.88; P < 0.001], PFS (median 3.1 versus 8.3 months; RR: 0.38; 95% CI: 0.26
      0.56; P < 0.001) and OS (median 10.9 versus 17.7 months; RR: 0.53; 95% CI: 0.34
      0.82; P < 0.001). CONCLUSIONS: Compared with patients with rising CEA, flare was
      an independent favourable predictive and prognostic factor for tumour response
      and survival.

PMID- 19861581
TI  - Where is the future of endometrial cancer therapy?

PMID- 19861582
TI  - Perception of orthodontic treatment need in children and adolescents.
AB  - SUMMARY: Patients' and parents' perception of malocclusion are important in
      determining orthodontic treatment demand, motivation, and cooperation. The aim of
      this study was to investigate differences in perception of treatment need in
      currently orthodontically treated, previously treated, and untreated subjects.
      The sample comprised 3196 children and adolescents (1593 males and 1603 females)
      aged 8-19 years (mean age 13.0 +/- 3.6 years) from 24 randomly selected public
      schools in Zagreb, Croatia. Objective treatment need was assessed clinically
      using the Dental Aesthetic Index (DAI). Subjective treatment need was estimated
      separately by an orthodontic resident, the child/adolescent and his/her parent
      using the Standardized Continuum of Aesthetic Need (SCAN) procedure. The
      children/adolescents completed a questionnaire that had five questions with five
      point Likert-type scale answers concerning satisfaction with dental appearance,
      importance of teeth for facial appearance, and malocclusion-related quality of
      life. Spearman correlation and logistic regression were used for statistical
      analysis. Associations between objective and subjective orthodontic treatment
      need were weak but statistically significant (Rho from 0.20 to 0.50; P < 0.05).
      Malocclusion-related quality of life was poorly associated with treatment need.
      Satisfaction with tooth appearance showed the most frequent statistically
      significant correlation (Rho from -0.14 to -0.35; P < 0.05), while importance of
      aligned teeth for facial appearance and social contacts had the weakest
      correlation with treatment need. Perception of treatment need was greater in
      previously treated subjects. Parents' perception had a low predictive value. The
      findings of this study show that malocclusion has more impact on emotional well
      being than on function or social contacts.

PMID- 19861583
TI  - Peroxisome proliferator-activated receptor-gamma regulates the expression and
      function of very-low-density lipoprotein receptor.
AB  - Very-low-density lipoprotein receptor (VLDLR) is a member of the low-density
      receptor family, highly expressed in adipose tissue, heart, and skeletal muscle.
      It binds apolipoprotein E-triglyceride-rich lipoproteins and plays a significant
      role in triglyceride metabolism. PPARgamma is a primary regulator of lipid
      metabolism in adipocytes and controls the expression of an array of genes
      involved in lipid trafficking in adipocytes. However, it is not known whether
      VLDLR is also under the control of PPARgamma. In this study, we investigated the
      role of PPARgamma in the regulation of VLDLR expression and function in vivo and
      in vitro. During the differentiation of 3T3-L1 preadipocytes, the levels of VLDLR
      protein and mRNA increased in parallel with the induction of PPARgamma expression
      and reached maximum in mature adipocytes. Treatment of differentiated adipocytes
      with PPARgamma agonist pioglitazone upregulated VLDLR expression in dose- and
      time-dependent manners. In contrast, specific inhibition of PPARgamma
      significantly downregulated the protein level of VLDLR. Induction of VLDLR is
      also demonstrated in vivo in adipose tissue of wild-type (WT) mice treated with
      pioglitazone. In addition, pioglitazone increased plasma triglyceride-rich
      lipoprotein clearance and increased epididymal fat mass in WT mice but failed to
      induce similar effects in vldlr(-/-) mice. These results were further
      corroborated by the finding that pioglitazone treatment enhanced adipogenesis and
      lipid deposition in preadipocytes of WT mice, while its effect in VLDLR-null
      preadipocytes was significantly blunted. These findings provide direct evidence
      that VLDLR expression is regulated by PPARgamma and contributes in lipid uptake
      and adipogenesis.

PMID- 19861584
TI  - Interactions between neurotensin and GnRH neurons in the positive feedback
      control of GnRH/LH secretion in the mouse.
AB  - In female mammals, increased ovarian estradiol (E(2)) secretion triggers GnRH
      release from neurons in the basal forebrain, which drives LH secretion from the
      pituitary and subsequently induces ovulation. However, the neural circuits that
      activate this preovulatory GnRH/LH surge remain unidentified. Neurotensin is
      expressed in neurons of the anteroventral periventricular nucleus (AVPV), a
      region thought to be critical for generating the preovulatory GnRH/LH surge. E(2)
      induces neurotensin (Nts) gene expression in this region, and blockade of
      neurotensin signaling reduces the LH surge in the rat. We postulated that
      neurotensin signaling plays a similar role in generating the E(2)-induced GnRH/LH
      surge in mice. We used in situ hybridization (ISH) to determine whether E(2)
      induces Nts expression in the mouse and found evidence to support this
      proposition. Next, we determined that the neurotensin receptor (Ntsr2) is present
      in many GnRH-expressing neurons. Since the kisspeptin gene (Kiss1) is expressed
      in the AVPV and is responsive to E(2), we predicted that some neurons in this
      region express both Kiss1 and Nts; however, by double-label ISH, we observed no
      coexpression of the two mRNAs. We also postulated that Nts mRNA expression would
      increase in parallel with the E(2)-induced LH surge and that the central (icv)
      administration of neurotensin would stimulate LH secretion and activation of GnRH
      neurons but found no evidence to support either of these hypotheses. Together,
      these findings suggest that, although neurotensin neurons in the AVPV are targets
      for regulation by E(2), neurotensin does not appear to play a direct role in
      generating the GnRH/LH surge in the mouse.

PMID- 19861585
TI  - Apelin is necessary for the maintenance of insulin sensitivity.
AB  - The recently discovered peptide apelin is known to be involved in the maintenance
      of insulin sensitivity. However, questions persist regarding its precise role in
      the chronic setting. Fasting glucose, insulin, and adiponectin levels were
      determined on mice with generalized deficiency of apelin (APKO). Additionally,
      insulin (ITT) and glucose tolerance tests (GTT) were performed. To assess the
      impact of exogenously delivered apelin on insulin sensitivity, osmotic pumps
      containing pyroglutamated apelin-13 or saline were implanted in APKO mice for 4
      wk. Following the infusion, ITT/GTTs were repeated and the animals euthanized.
      Soleus muscles were harvested and homogenized in lysis buffer, and insulin
      induced Akt phosphorylation was determined by Western blotting. Apelin-13
      infusion and ITTs/GTTs were also performed in obese diabetic db/db mice. To probe
      the underlying mechanism for apelin's effects, apelin-13 was also delivered to
      cultured C2C12 myotubes. 2-[3H]deoxyglucose uptake and Akt phosphorylation were
      assessed in the presence of various inhibitors. APKO mice had diminished insulin
      sensitivity, were hyperinsulinemic, and had decreased adiponectin levels. Soleus
      lysates had decreased insulin-induced Akt phosphorylation. Administration of
      apelin to APKO and db/db mice resulted in improved insulin sensitivity. In C2C12
      myotubes, apelin increased glucose uptake and Akt phosphorylation. These events
      were fully abrogated by pertussis toxin, compound C, and siRNA knockdown of
      AMPKalpha1 but only partially diminished by LY-294002 and not at all by L-NAME.
      We conclude that apelin is necessary for the maintenance of insulin sensitivity
      in vivo. Apelin's effects on glucose uptake and Akt phosphorylation are in part
      mediated by a G(i) and AMPK-dependent pathway.

PMID- 19861586
TI  - Endocrine pulse identification using penalized methods and a minimum set of
      assumptions.
AB  - The detection of hormone secretion episodes is important for understanding normal
      and abnormal endocrine functioning, but pulse identification from hormones
      measured with short interval sampling is challenging. Furthermore, to obtain
      useable results, the model underlying hormone secretion and clearance must be
      augmented with restrictions based on biologically acceptable assumptions. Here,
      using the assumption that there are only a few time points at which a hormone is
      secreted, we used a modern penalized nonlinear least-squares setup to select the
      number of secretion events. We did not assume a particular shape or frequency
      distribution for the secretion pulses. Our pulse identfication method, VisPulse,
      worked well with luteinizing hormone (LH), cortisol, growth hormone, or
      testosterone. In particular, applying our modeling strategy to previous LH data
      revealed a good correlation between the modeled and measured LH hormone
      concentrations, the estimated secretion pattern was sparse, and the small and
      structureless residuals indicated a proper model with a good fit. We benchmarked
      our method to AutoDecon, a commonly used hormone secretion model, and performed
      releasing hormone infusion experiments. The results of these experiments
      confirmed that our method is accurate and outperforms AutoDecon, especially for
      detecting silent periods and small secretion events, suggesting a high-secretion
      event resolution. Method validation using (releasing hormone) infusion data
      revealed sensitivities and selectivities of 0.88 and 0.95 and of 0.69 and 0.91
      for VisPulse and AutoDecon, respectively.

PMID- 19861587
TI  - Constitutively active calcineurin in skeletal muscle increases endurance
      performance and mitochondrial respiratory capacity.
AB  - Expression of an activated form of calcineurin in skeletal muscle selectively up
      regulates slow-fiber-specific gene expression. Here, we tested the hypothesis
      that expression of activated calcineurin in skeletal muscle influences body
      composition, energy homeostasis, and exercise performance. Using transgenic mice
      expressing activated calcineurin (CnA*) in skeletal muscle (MCK-CnA* transgenic
      mice), we determined whether skeletal muscle reprogramming by calcineurin
      activation affects exercise performance and skeletal muscle mitochondrial
      function. Body weight and extensor digitorum longus (EDL) skeletal muscle weight
      were reduced 10% in MCK-CnA* mice compared with wild-type littermates. Basal
      oxygen consumption, food intake, and voluntary exercise behavior were unchanged
      between MCK-CnA* and wild-type mice. However, when total energy expenditure was
      normalized by fat-free mass, energy expenditure was increased in MCK-CnA* mice.
      An endurance performance treadmill running test revealed MCK-CnA* mice are
      fatigue resistant and run 50% farther before exhaustion. After a standardized
      exercise bout, glycogen and triglyceride content in EDL muscle was higher in MCK
      CnA* vs. wild-type mice. Mitochondrial respiratory capacity was increased 35% in
      EDL muscle from resting MCK-CnA* mice. In conclusion, our results provide
      evidence to support the hypothesis that calcineurin activation in skeletal muscle
      increases mitochondrial oxidative function and energy substrate storage, which
      contributes to enhanced endurance exercise performance. These adaptive changes
      occur as a consequence of a lifelong expression of a constitutively active
      calcineurin and mimic the response to chronic endurance training.

PMID- 19861589
TI  - Semantic event-related potential components reflect severity of comprehension
      deficits in aphasia.
AB  - BACKGROUND AND OBJECTIVES: Several cognitive event-related potential (ERP)
      components such as mismatch negativity, P300, N400, and the late positive
      component (LPC) have been studied in aphasia. The aim of this study was to
      determine whether a modified semantic incongruity paradigm can serve as a more
      graded differentiation of ERP changes in patients with mild versus severe
      comprehension deficits. METHODS: A total of 20 aphasic patients with minor and
      severe comprehension deficits and 20 young and elderly healthy controls were
      examined while reading 4-word sentences ending in a semantically congruent or
      noncongruent word. RESULTS: In contrast to young controls and to patients with
      mild comprehension deficits, aphasic patients with severe comprehension deficits
      exhibit an early positivity in the time window from 200 to 400 milliseconds and
      no N400 after the presentation of nonrecurrent semantically incongruent words.
      Patients with mild comprehension deficits were found to have an N400 with
      prolonged latency in comparison with the controls. An age effect in the control
      groups was detected as well. DISCUSSION: Semantic access and integration are
      performed differently in aphasic subjects with severe comprehension deficits.
      These differences in lexical-semantic processing must be taken into account in
      rehabilitation approaches that aim to improve comprehension deficits. Moreover,
      the findings may contribute to the design of therapy studies by employing a
      physiological measure that can discriminate among patients at baseline and at the
      end of an intervention.

PMID- 19861588
TI  - The effect of different patterns of growth hormone administration on the IGF axis
      and somatic and skeletal growth of the dwarf rat.
AB  - Normal childhood growth is determined by ultradian and infradian variations in GH
      secretion, yet GH treatment of children with short stature is restricted to daily
      fixed doses. We have used GH-deficient dwarf rats to determine whether variable
      GH dose regimens promote growth more effectively than fixed doses. Animals were
      treated with saline or 4.2 mg of recombinant bovine GH given as 1) 700 microg/wk
      in 100 microg/day doses, 2) alternating weekly doses of 966 (138 microg/day) or
      434 microg (62 microg/day), or 3) 700 microg/wk in randomized daily doses (5-250
      microg/day). Body weight and length were measured weekly. Femur and tibia lengths
      and internal organ, fat pad, and muscle weights were recorded at the end of the
      study (6 wk); blood was collected for IGF axis measurements. GH promoted femur
      [F(3,60) = 14.67, P < 0.05], tibia [F(3,60) = 14.90, P < 0.05], muscle [F(3,60) =
      10.37, P < 0.05], and organ growth [liver: F(3,60) = 9.30, P < 0.05; kidney:
      F(3,60) = 2.82, P < 0.05] and an increase in serum IGF-I [F(3,60) = 9.18, P <
      0.05] and IGFBP-3 [F(3,60) = 6.70, P < 0.05] levels. IGF-I levels correlated with
      final weight (r = 0.45, P < 0.05) and length (r = 0.284, P < 0.05) in the whole
      cohort, but within each group, growth parameters correlated with serum IGF-I only
      in animals treated with random GH doses. The variable regimens promoted femur
      length (P < 0.05) and muscle (P < 0.05) and kidney (P < 0.05) weight more
      effectively than treatment with the fixed regimen. This study demonstrates that
      aspects of growth are improved following introduction of infradian variation to
      GH treatment in a GH-deficient model. The data suggest that varying the pattern
      of GH doses administered to children may enhance growth performance without
      increasing the overall GH dose.

PMID- 19861590
TI  - Does functional electrical stimulation for foot drop strengthen corticospinal
      connections?
AB  - BACKGROUND: Long-term use of a foot-drop stimulator applying functional
      electrical stimulation (FES) to the common peroneal nerve improves walking
      performance even when the stimulator is off. This "therapeutic" effect might
      result from neuroplastic changes. OBJECTIVE: To determine the effect of long-term
      use of a foot-drop stimulator on residual corticospinal connections in people
      with central nervous system disorders. METHODS: Ten people with nonprogressive
      disorders (eg, stroke) and 26 with progressive disorders (eg, multiple sclerosis)
      used a foot-drop stimulator for 3 to 12 months while walking in the community.
      Walking performance and electrophysiological variables were measured before and
      after FES use. From the surface electromyogram of the tibialis anterior muscle,
      we measured the following: (1) motor-evoked potential (MEP) from transcranial
      magnetic stimulation over the motor cortex, (2) maximum voluntary contraction
      (MVC), and (3) maximum motor wave (M(max)) from stimulating the common peroneal
      nerve. RESULTS: After using FES, MEP and MVC increased significantly by
      comparable amounts, 50% and 48%, respectively, in the nonprogressive group and
      27% and 17% in the progressive group; the changes were positively correlated
      (R(2) = .35; P < .001). Walking speed increased with the stimulator off
      (therapeutic effect) by 24% (P = .008) and 7% (P = .014) in the nonprogressive
      and progressive groups, respectively. The changes in M(max) were small and not
      correlated with changes in MEP. CONCLUSIONS: The large increases in MVC and MEP
      suggest that regular use of a foot-drop stimulator strengthens activation of
      motor cortical areas and their residual descending connections, which may explain
      the therapeutic effect on walking speed.

PMID- 19861591
TI  - Does provision of extrinsic feedback result in improved motor learning in the
      upper limb poststroke? A systematic review of the evidence.
AB  - BACKGROUND: Recovery of the upper limb (UL) after a stroke occurs well into the
      chronic stage. Stroke survivors can benefit from adaptive plasticity to improve
      UL movement through motor relearning. The provision of feedback has been shown to
      decrease the use of compensatory UL movement patterns. However, the effectiveness
      of feedback in improving UL motor recovery after a stroke has not yet been
      systematically reviewed. OBJECTIVE: The objective of this review was to
      systematically examine the role of extrinsic feedback on implicit motor learning
      after stroke, focusing on UL movement and functional recovery. RESULTS: The
      authors retrieved 9 studies that examined the role of feedback on UL motor
      recovery. Of these, 6 were randomized controlled trials (RCTs), 1 was a single
      subject design, 1 was a pre-post design, and 1 was a cohort study. The studies
      were rated on the basis of Sackett's levels of evidence and PEDro (Physiotherapy
      Evidence Database) scores for RCTs. Levels of evidence were limited (level 2b)
      for UL motor learning of the less-affected extremity and strong (level 1a) for
      the more-affected extremity. DISCUSSION AND CONCLUSIONS: The results suggest that
      people with stroke may be capable of using extrinsic feedback for implicit motor
      learning and improving UL motor recovery. Emergent questions regarding the
      advantages of using different media for feedback delivery and the optimal type
      and schedule of feedback to enhance motor learning in patient populations still
      need to be addressed.

PMID- 19861592
TI  - Personality types and performance: COMLEX-USA Level 2-CE.

PMID- 19861593
TI  - Personality types and performance on aptitude and achievement tests.

PMID- 19861594
TI  - Association among cardiorespiratory fitness, body fat, and bone marker
      measurements in healthy young females.
AB  - CONTEXT: Serum vitamin D (25-hydroxyvitamin D [25(OH)D]) is important for
      maintaining bone health, as well as for influencing a multitude of nonosseous
      effects. Associations between 25(OH)D and other bone marker measurements have not
      been well studied in relation to obesity and cardiorespiratory fitness in healthy
      young females. OBJECTIVE: To determine if there is an association of
      cardiorespiratory fitness and body fat with bone marker measurements (ie, 25[OH]D
      and calcium) in healthy young females at peak bone mass. METHODS: Females younger
      than 25 years were recruited as volunteer participants. From July 2007 to October
      2007, participants were assessed for cardiorespiratory fitness by measuring
      maximal oxygen consumption (VO(2) max). In addition, their levels of serum
      25(OH)D and serum total calcium were analyzed. Finally, percent body fat was
      measured using dual-energy x-ray absorptiometry of the whole body. Pearson
      correlation coefficients were used to evaluate the association of fitness and
      body fat with bone marker measurements. RESULTS: A total of 59 adolescent girls
      and young women-were recruited. A statistically significant, positive association
      was found between VO(2) max and serum 25(OH)D levels (Pearson r=0.36; P<.05), but
      not between VO(2) max and serum total calcium levels (Pearson r= -0.10, P>.05).
      Percent body fat was inversely associated with both VO(2) max (Pearson r= -0.70,
      P<.05) and 25(OH)D levels (Pearson r= -0.44, P<.05). CONCLUSION: In healthy young
      females, better cardiorespiratory fitness, as measured by VO(2) max level, and
      lower percent body fat are associated with higher serum 25(OH)D level. This
      response is independent of serum total calcium level.

PMID- 19861595
TI  - Epiphrenic esophageal diverticula: spectrum of symptoms and consequences.
AB  - Patients with esophageal diverticula may present with a variety of symptoms. Many
      of these symptoms mimic less serious disease, making diagnosis of esophageal
      diverticulum difficult for many primary care physicians. Delayed or missed
      diagnosis of this disorder may lead to more serious problems including
      gastrointestinal bleeding, aspiration pneumonia, and cancer. Our case series
      illustrates a variety of symptoms observed among three patients who were
      diagnosed and surgically treated for esophageal diverticulum. Appropriate
      diagnosis and management of esophageal diverticulum results in resolution of
      symptoms and decreased risk of morbidity.

PMID- 19861596
TI  - Moyamoya disease: case report and literature review.
AB  - Moyamoya disease is a chronic, progressive occlusion of the circle of Willis
      arteries that leads to the development of characteristic collateral vessels seen
      on imaging, particularly cerebral angiography. The disease may develop in
      children and adults, but the clinical features differ. Moyamoya disease occurs
      predominantly in Japanese individuals but has been found in all races with
      varying age distributions and clinical manifestations. As a result, moyamoya
      disease has been underrecognized as a cause of ischemic and hemorrhagic strokes
      in Western countries. At this time, there is no known cure, and existing
      treatment options are controversial. The authors describe the case of a 44-year
      old African American woman with a history of hypertension, cervical cancer,
      breast cancer, and stroke who was diagnosed as having moyamoya disease. A review
      of the literature for the various facets of this condition is also provided.

PMID- 19861597
TI  - Do not exclude IMGs.

PMID- 19861598
TI  - Maintaining distinctiveness and affordability of osteopathic medical education.

PMID- 19861601
TI  - Tache noire in African tick bite fever.

PMID- 19861602
TI  - African tick bite Fever in a Taiwanese traveler returning from South Africa:
      molecular and serologic studies.
AB  - We report the first imported case of African tick bite fever (ATBF) in a patient
      from Taiwan who returned from a 10-day trip to South Africa. Diagnosis was
      confirmed by polymerase chain reaction (PCR) from eschar biopsies. Portions of
      rickettsial ompA (491 bp) and ompB (273 bp) genes were amplified and subsequent
      sequencing of PCR product showed its 100% identity with R. africae.
      Microimmunofluorescence (MIF) assay of patient's serum on Days 14 and 46 after
      the onset of illness revealed IgG seroconversion when tested with spotted fever
      group (SFG) rickettsiae antigens, including R. africae. The patient clinically
      improved on the third day of 14-day treatment with a combination of ciprofloxacin
      and minocycline. Based on the patient's travel history and chronology of clinical
      symptoms, we strongly suspect that the tick-biting event occurred in Kruger
      National Park.

PMID- 19861603
TI  - Successful sporozoite challenge model in human volunteers with Plasmodium vivax
      strain derived from human donors.
AB  - Successful establishment of a Plasmodium vivax sporozoite challenge model in
      humans is described. Eighteen healthy adult, malaria-naive volunteers were
      randomly allocated to Groups A-C and exposed to 3 +/- 1, 6 +/- 1, and 9 +/- 1
      bites of Anopheles albimanus mosquitoes infected with P. vivax, respectively.
      Seventeen volunteers developed signs and symptoms consistent with malaria, and
      geometric mean prepatent periods of 11.1 days (9.3-11) for Group A; 10.8 days
      (9.8-11.9) for Group B; and 10.6 days (8.7-12.4) for Group C, with no
      statistically significant difference among groups (Kruskal-Wallis, P = 0.70). One
      volunteer exposed to eight mosquito bites did not develop a parasitemia. No
      differences in parasite density were observed and all individuals successfully
      recovered after anti-malarial treatment. None of the volunteers developed
      parasite relapses within an 18-month follow-up. In conclusion, malaria-naive
      volunteers can be safely and reproducibly infected with bites of 2-10 An.
      albimanus mosquitoes carrying P. vivax sporozoites. This challenge method is
      suitable for vaccine and anti-malarial drug testing.

PMID- 19861604
TI  - Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline
      in healthy subjects.
AB  - We evaluated whether sex affects the steady-state pharmacokinetics of the
      antimalarial drugs, primaquine and doxycycline, in healthy subjects. Seventeen
      male and 17 female healthy Vietnamese subjects were administered 30 mg (base) of
      primaquine daily for 14 days. After a 2-week washout period, 14 male and 14
      female subjects were administered 100 mg (base) of doxycycline daily for 14 days.
      Women had significantly higher median values of C(max) (212 versus 122 ng/mL, P<
      0.001) and AUC(0-24) (1,909 versus 917 ng . h/mL, P < 0.001) of primaquine
      compared with men. Other than a longer t(max) in women, no sex-related
      differences were seen in the pharmacokinetics of doxycycline. The primaquine
      pharmacokinetic data suggest that women have increased exposure to primaquine,
      which may put them at increased risk for toxicity when administered the same
      maintenance dose as men. The similar pharmacokinetics of doxycycline between the
      two sexes justifies the same maintenance dose.

PMID- 19861606
TI  - Histopathology of fatal respiratory distress caused by Plasmodium vivax malaria.
AB  - An otherwise healthy 20-year-old woman in Goa, India, received antibiotics after
      a diagnosis of upper respiratory tract infection. One week later, vivax malaria
      was diagnosed at a health center, but the patient developed respiratory distress
      and lost consciousness. She arrived at emergency department in shock, breathless,
      and comatose. She died within minutes. Two independent laboratories later
      confirmed Plasmodium vivax by microscopy (140,000/microL) and by nested and real
      time polymerase chain reaction methods. Post-mortem examination showed congestion
      of alveolar capillaries by heavy monocytic infiltrates, along with diffuse damage
      to alveolar membranes consistent with acute respiratory distress syndrome.
      Parasites seen in lung tissue were roughly proportionate to both peripheral
      hyperparasitemia and those seen in other organs without lesions. In this patient,
      vivax malaria caused a rapidly fatal respiratory distress.

PMID- 19861605
TI  - Malaria diagnosis by a polymerase chain reaction-based assay using a pooling
      strategy.
AB  - Pooling clinical specimens reduces the number of assays needed when screening for
      infectious diseases. Polymerase chain reaction (PCR)-based assays are the most
      sensitive tests to diagnose malaria, but its high cost limits its use. We adapted
      a pooling platform that could reduce the number of assays needed to detect
      malaria infection. To evaluate this platform, two sets of 100 serum samples, with
      1% and 5% malaria prevalence, were tested. DNA, extracted from pooled samples,
      was amplified by malaria-specific PCR. Additional validation was performed by
      determining the level of PCR detection based on 1:10 and 1:100 dilution. The
      platform correctly detected all malaria samples in the two test matrices. The use
      of stored serum samples also has important implications for studies investigating
      malaria prevalence rates retrospectively. Field studies, using serum and whole
      blood specimens, are needed to validate this technique for the adaptation of
      these methods for clinical utility.

PMID- 19861607
TI  - Absence of asymptomatic malaria infections in previously high endemic areas of
      Sri Lanka.
AB  - As the goal of malaria elimination from Sri Lanka is currently being pursued,
      this study was planned to determine the prevalence of asymptomatic malaria
      infections. Five health areas in Trincomalee and Kurunegala districts that
      reported high prevalence in the recent past were purposively selected. The
      smallest administrative units (GN divisions) having high malaria risk within each
      area were identified. From these divisions, 20% of the population was randomly
      selected for blood smear examination and in a 50% sub-sample polymerase chain
      reaction (PCR) assay was performed. A population of 3,730 from 13 GN divisions
      was sampled. Thick and thin Giemsa-stained blood smears were negative for malaria
      parasites. The PCR carried out in 50% of the study sample was also negative for
      malaria parasites. The findings illustrate the absence of asymptomatic carriers
      in previously high transmission areas and it appears that achieving malaria
      elimination in Sri Lanka by 2015 is feasible.

PMID- 19861608
TI  - Budd-Chiari syndrome as a vascular complication of amebic liver abscess.
AB  - Amebiasis remains a major public health issue in most of the world. Amebic liver
      abscess is the most common extraintestinal manifestation. A complication such as
      venous obstruction associated with amebiais is rare. We report a thrombosis in
      hepatic veins associated with amebic hepatic abscess in a traveler.

PMID- 19861609
TI  - Seasonal pattern of pneumonia mortality among under-five children in Nairobi's
      informal settlements.
AB  - Using longitudinal data from the Nairobi Urban and Demographic Surveillance
      System (NUHDSS), we examined the seasonal pattern of pneumonia mortality among
      under-five children living in Nairobi's slums. We included 17,787 under-five
      children resident in the NUHDSS from January 1, 2003 to December 31, 2005 in the
      analysis. Four hundred thirty-six deaths were observed and cause of death was
      ascertained by verbal autopsy for 377 of these deaths. Using Poisson regression,
      we modeled the quarterly mortality risk for pneumonia. The overall person-years
      (PYs) were 21,804 giving a mortality rate of 20.1 per 1,000 PYs in the study
      population. Pneumonia was the leading cause of death contributing 25.7% of the
      total deaths. Pneumonia mortality was highest in the second quarter (risk ratio
      [RR] = 2.3, confidence interval [CI]: 1.2-4.2 compared with the fourth quarter).
      The study provides evidence that pneumonia-related mortality among under-fives in
      Nairobi's slums is higher from April to June corresponding to the rainy season
      and the beginning of the cold season.

PMID- 19861610
TI  - Influence of tropical climate conditions on the quality of antihypertensive drugs
      from Rwandan pharmacies.
AB  - The objective of this study was to assess the quality of antihypertensive drugs
      and to investigate the influence of tropical storage conditions. Drug content and
      in vitro dissolution tests were performed on 10 test formulations (from Rwanda)
      and 6 reference formulations (from Belgium or France) after purchase and after 6
      month storage under long-term (25 +/- 2 degrees C and 60 +/- 5% relative humidity
      [RH]) and accelerated (40 +/- 2 degrees C and 75 +/- 5% RH) testing conditions.
      Twenty percent of test formulations were of substandard content at the time of
      purchase. After 6 months at accelerated testing conditions, 7 of 10 test
      formulations were substandard in content and 8 were substandard for the combined
      criteria of drug content and dissolution, whereas no reference drug became
      substandard. This study shows that, apart from some drugs being already
      substandard from purchase, accelerated testing conditions (simulating tropical
      climate) have deleterious effects on the majority of antihypertensive drug
      formulations found in the Rwandan market.

PMID- 19861611
TI  - A simplified, low-cost method for polarized light microscopy.
AB  - Malaria pigment is an intracellular inclusion body that appears in blood and
      tissue specimens on microscopic examination and can help in establishing the
      diagnosis of malaria. In simple light microscopy, it can be difficult to discern
      from cellular background and artifacts. It has long been known that if polarized
      light microscopy is used, malaria pigment can be much easier to distinguish.
      However, this technique is rarely used because of the need for a relatively
      costly polarization microscope. We describe a simple and economical technique to
      convert any standard light microscope suitable for examination of malaria films
      into a polarization microscope.

PMID- 19861612
TI  - Spatial distribution of female genital mutilation in Nigeria.
AB  - The harmful effects of female genital mutilation (FGM) on women are recognized
      worldwide. Although it is practiced by persons of all socioeconomic backgrounds,
      there are differences within countries and between communities. The aim of this
      study was to use the 2003 Nigeria Demographic and Health Survey data to determine
      the spatial distribution of the prevalence of FGM and associated risk factors.
      Data were available for 7,620 women; 1,673 (22.0%) interviewed had had FGM and
      2,168 women had living children, of whom 485 (22.4%) daughters had undergone FGM.
      Unmarried women were more likely to report a lower prevalence of FGM.
      Modernization (education and high socioeconomic status) had minimal impact on the
      likelihood of FGM, but education plays an important role in the mother's decision
      not to circumcise her daughter. It follows from these findings that community
      factors have a large effect on FGM, with individual factors having little effect
      on the distribution of FGM.

PMID- 19861613
TI  - Integrating NTD mapping protocols: Can surveys for trachoma and urinary
      schistosomiasis be done simultaneously?
AB  - We determined whether the school-based "disease mapping" methodology used to
      assess urinary schistosomiasis (SCH) is useful for determining trachoma
      interventions and whether the district-based approach recommended for trachoma is
      useful for SCH control programs. We conducted two separate integrated surveys in
      eight districts of central Nigeria: school based and district based. A total of
      17,189 children were examined for trachoma and 16,238 children were examined for
      hematuria from 363 schools and 2,149 households. School surveys identified 67
      communities warranting praziquantel drug treatment of SCH and 142 trachoma
      endemic communities warranting trachoma control activities. In district-level
      estimates, we identified 24 communities for praziquantel treatment and 0 for
      trachoma intervention. Integrating trachoma into SCH school-based surveys, and
      SCH into trachoma surveys, was quick and easy, but in this setting, school-based
      surveys were more useful for identifying communities where intervention is
      warranted.

PMID- 19861614
TI  - Geographic distribution and prevalence of schistosomiasis and soil-transmitted
      helminths among schoolchildren in Mozambique.
AB  - Schistosomiasis and soil-transmitted helminths (STHs) are most prevalent in
      developing countries. In Mozambique, the first and only national survey of the
      distribution and prevalence of schistosomiasis and STHs was conducted in 1952 and
      1957. Only occasional surveys in restricted areas have been conducted since the
      1950s. The objective of our survey was to update information on the geographic
      distribution and prevalence of schistosomiasis and STHs in this country. During
      August 2005-June 2007, the Schistosomiasis and STH Laboratory of National
      Institutes of Health of the Ministry of Health undertook an epidemiologic survey
      among schoolchildren. A total of 83,331 persons attending primary schools were
      sampled. The mean age was 11.36 years (range: 7-22 years). Stool and urine
      samples were collected and examined by using Kato-Katz and filtration and Ritchie
      and Willis techniques. Results indicate a widespread occurrence of Schistosoma
      haematobium (overall prevalence = 47.0%) and STHs (prevalence = 53.5%).
      Prevalence varied dramatically across the country, with the highest prevalence in
      districts in northern provinces (Cabo Delgado, Niassa, Nampula, and Zambezia) and
      in certain provincial capital cities. Districts in the southern region of the
      country were less affected. Schistosoma mansoni was less common, with prevalence
      of 1%. We conclude that schistosomiasis and STHs are widely distributed in
      Mozambique and confirm the need for a national helminth control program.

PMID- 19861615
TI  - Interleukin-1 beta single-nucleotide polymorphism's C allele is associated with
      elevated risk of gastric cancer in Helicobacter pylori-infected Peruvians.
AB  - Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with
      increased risk of atrophic gastritis and gastric cancer in the populations of
      East Asia and Europe. No such data exist from Peru, a developing country with a
      population genotypically different from others studied and with a high prevalence
      of Helicobacter pylori infection and gastric cancer. We conducted a case-control
      study comparing 334 hospitalized patients with atrophic gastritis or gastric
      cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic
      regression analysis revealed that an increased risk of atrophic gastritis (odds
      ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B
      511 C allele. Our study is the first to establish this allele as a risk for these
      conditions. Given the high prevalence of H. pylori and recurrence rate after
      treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those
      individuals who would benefit most from robust H. pylori eradication efforts in
      Peru.

PMID- 19861616
TI  - Prevalence and genetic heterogeneity of Bartonella strains cultured from rodents
      from 17 provinces in Thailand.
AB  - To study the distribution and diversity of Bartonella in rodents from Thailand,
      330 rodents belonging to 13 species were tested. The majority (80.6%) of rodents
      examined belonged to the genus Rattus. Bartonellae were cultured from 41.5% of
      the rodents with a wide range of prevalence by host species and regions.
      Sequencing of gltA revealed diverse Bartonella strains. Bartonellae from Rattus
      spp. belonged to 23 variants and clustered with Bartonella coopersplainensis,
      Bartonella elizabethae, Bartonella phoceensis, Bartonella rattimassiliensis,
      Bartonella tribocorum, and an unknown geno-group. Bartonellae from Bandicota spp.
      belonged to six variants and clustered with B. coopersplainensis, B.
      rattimassilliensis, and B. tribocorum. Three variants from Mus spp. clustered
      with B. coopersplainensis or B. rattimassilliensis. The only isolate from a
      Berylmys berdmorei fell into the B. tribocorum group. The observations highlight
      the need to study these agents for their role in human febrile illnesses of
      unknown etiology in Thailand and elsewhere in Asia.

PMID- 19861617
TI  - Translational regulation by the 3' untranslated region of the dengue type 2 virus
      genome.
AB  - The role of the 3'untranslated region (UTR) of the dengue virus (DENV) genome
      during viral translation remains to be elucidated. We assessed the contribution
      of well-defined RNA elements in the 3'UTR of DENV-2 to viral translation using a
      virus-induced reporting gene system and deoxyribozymes (DRzs) targeting the 3'UTR
      of the DENV-2 genome. Results show that mRNAs carrying a deletion of repeated
      conserved sequence (RCS2)-CS2 are translated less efficiently than wild type
      mRNAs. However, mRNAs with a deletion of CS1-stem loop (SL) are translated more
      efficiently. Thus, CS1-SL and RCS2-CS2 may have different effects on
      translational regulation. Additionally, the translation-suppressing effect of CS1
      SL or the SL element is further confirmed in DENV-2-infected cells using DRzs.
      Mutagenesis studies show that, rather than the secondary structure, nucleotides
      10663-10677 and 10709-10723 are responsible for translational suppression of SL.
      Overall, our results demonstrate that sequences and elements within the DENV-2
      3'UTR regulate viral translation.

PMID- 19861618
TI  - Dengue plaque reduction neutralization test (PRNT) in primary and secondary
      dengue virus infections: How alterations in assay conditions impact performance.
AB  - Dengue virus (DENV) infection is a worsening global health problem. The plaque
      reduction neutralization test (PRNT) is currently considered to be the "gold
      standard" to characterize and quantify circulating levels of anti-DENV
      neutralizing antibody (NAb). Many variations of the PRNT are currently in use and
      neither the assay nor its performance conditions have been standardized or
      harmonized between laboratories. We used a well-characterized panel of acute and
      late convalescent follow-up sera samples from children experiencing primary and
      secondary DENV infections to evaluate the performance of the dengue PRNT under a
      variety of testing conditions. Investigators varied cell type, control virus
      passage, and the use of complement across multiple assay runs of the same sample
      panel. Our findings indicate wide variation in PRNT titer results in response to
      varied testing conditions.

PMID- 19861619
TI  - Phase 1 trial of the dengue virus type 4 vaccine candidate rDEN4{Delta}30-4995 in
      healthy adult volunteers.
AB  - rDEN4Delta30-4995 is a live attenuated dengue virus type 4 (DENV4) vaccine
      candidate specifically designed as a further attenuated derivative of the
      rDEN4Delta30 parent virus. In a previous study, 5 of 20 vaccinees who received
      10(5) plaque-forming units (PFU) of rDEN4Delta30 developed a transient elevation
      of the serum alanine aminotransferase (ALT) level and an asymptomatic
      maculopapular rash developed in 10 of 20. In the current study, 28 healthy adult
      volunteers were randomized to receive 10(5) PFU of rDEN4Delta30-4995 (20) or
      placebo (8) as a single subcutaneous injection. The vaccine was safe, well
      tolerated, and immunogenic. An asymptomatic generalized maculopapular rash and
      elevations in ALT levels were observed in 10% of the rDEN4Delta30-4995 vaccinees.
      None of the rDEN4Delta30-4995 vaccinees became viremic, yet 95% developed a four
      fold or greater increase in neutralizing antibody titers. Thus, rDEN4Delta30-4995
      was demonstrated to be safe, highly attenuated, and immunogenic. However, an
      asymptomatic localized erythematous rash at the injection site was seen in 17/20
      rDEN4Delta30-4995 vaccinees. Therefore, alternative DENV4 vaccine strains were
      selected for further clinical development.

PMID- 19861620
TI  - Effects of latitude and longitude on the population structure of Culex pipiens
      s.l., vectors of West Nile virus in North America.
AB  - We assessed the structure and latitudinal selection that might result in
      sensitivities to critical day-lengths that trigger diapause between Culex pipiens
      populations distributed along North-South and East-West axes in eastern North
      America. Strong population structure between Cx. p. pipiens and Cx. p.
      quinquefasciatus existed. Among Cx. p. pipiens, a 100-km increase in the
      latitudinal change resulted in an increased square root of F(ST) by 0.002. A 100
      km increase in the longitudinal change caused an increased square root of F(ST)
      by 0.035. A lack of latitudinal influence on the structure between Cx. p. pipiens
      populations suggests a uniform signal using the 12 microsatellite markers, which
      might increase the risk of West Nile virus (WNV) transmission toward northern
      areas because of longer breeding season, extend host-seeking period, and larger
      population size. Northern Cx. p. pipiens may have undergone additional
      generations before diapause is triggered, magnifying population size when WNV
      amplification is peaking.

PMID- 19861621
TI  - Blood sources of mosquitoes collected from urban and peri-urban environments in
      eastern Australia with species-specific molecular analysis of avian blood meals.
AB  - To identify the hosts of mosquitoes collected from urban and peri-urban habitats
      in eastern Australia, 1,180 blood fed mosquitoes representing 15 species were
      analyzed by enzyme-linked immunosorbent assay and molecular techniques. Four
      common and epidemiologically important species could be classified according to
      their host-feeding patterns: Aedes aegypti was anthropophilic, Ae. vigilax was
      mammalophilic, Culex quinquefasciatus was ornithophilic, and Cx. annulirostris
      was opportunistic, readily feeding on birds and mammals. Mitochondrial cytochrome
      b DNA sequence data showed that more than 75% of avian blood meals identified
      from Cx. annulirostris collected from Brisbane, Newcastle, and Sydney originated
      from ducks (Order Anseriformes, Family Anatidae). More than 75% of avian blood
      meals from Cx. quinquefasciatus from Cairns belonged to one of three Passerine
      species, namely Sphecotheres vieilloti (figbird), Sturnus tristis (common myna),
      and Philemon buceroides (helmeted friarbird). This study demonstrates
      associations between vectors in Australia and vertebrate hosts of endemic and
      exotic arboviruses.

PMID- 19861622
TI  - Phylogeny of Triatoma sherlocki (Hemiptera: Reduviidae: Triatominae) inferred
      from two mitochondrial genes suggests its location within the Triatoma
      brasiliensis complex.
AB  - The phylogenetic position of Triatoma sherlocki within triatomines group was
      inferred by analyzing mtDNA fragments of Cyt B and 16S ribosomal RNA by using
      maximum parsimony and Bayesian analysis. Despite being differentiated from
      members of the T. brasiliensis complex on morphologic grounds, molecular
      phylogenetic analysis suggests T. sherlocki is a member of this complex;
      moreover, it was placed as a sister species of T. melanica. These suggestions
      were supported by robust credibility rates. Hence, we show evidence for the
      paraphyletic group of the "Triatoma brasiliensis complex," which should be
      composed of T. brasiliensis brasiliensis, T. brasiliensis macromelasoma, T.
      juazeirensis, T. melanica, and T. sherlocki.

PMID- 19861623
TI  - Chikungunya virus isolated from a returnee to Japan from Sri Lanka: isolation of
      two sub-strains with different characteristics.
AB  - A large-scale epidemic of chikungunya (CHIK) fever occurred in several Indian
      Ocean islands in 2004 and spread to India and Sri Lanka. In December 2006, a
      returnee to Japan from Sri Lanka developed an acute febrile illness. The patient
      was confirmed to have CHIK fever after reverse transcription-polymerase chain
      reaction, and specific IgM and IgG detection. CHIK virus was isolated from the
      serum specimen collected at the acute stage. The isolated virus developed two
      different sizes of plaques. Two sub-strains with different genetic and biological
      characteristics were obtained by plaque purification from one isolate. The entire
      genome was sequenced and phylogenetic analysis of the E1 genome showed that the
      sub-strains were of the Central/East African genotype, and were closely related
      to recent isolates in India. This is the first report of CHIK virus genome
      sequences isolated from a patient infected in Sri Lanka.

PMID- 19861624
TI  - Coverage of and influences on timely administration of hepatitis B vaccine birth
      dose in remote rural areas of the People's Republic of China.
AB  - A survey was conducted in 2006 to assess the coverage and timeliness of the birth
      dose of hepatitis B vaccine (HepB(1)) and related influences among children in
      rural areas of Guangxi, Guizhou, Tibet, and Shaanxi provinces, People's Republic
      of China. A total of 3,390 children born in 2004 were surveyed in four counties
      in each province, where a project to strengthen routine immunization is being
      implemented by the China Ministry of Health, supported by the United National
      Children's Fund. Two-stage stratified cluster sampling was undertaken to select
      those surveyed. A questionnaire was administered to parents or guardians and
      vaccination records were assessed. HepB(1) administration was timely for 31.6% of
      the sample. Timeliness of HepB(1) for children delivered at home (13%) was lower
      than for children born at county-level or higher facilities (54%) (odds ratio
      [OR] = 6.52, (95% confidence interval [CI] = 5.29-8.04, P < 10 (-3)), at township
      hospitals (49%, OR = 7.14, 95% CI = 5.68-8.98, P < 10 (-3)), or private clinics
      (59%, OR = 5.64, 95% CI = 3.68-8.64, P < 10 (-3)). Children of Tibetan (24.8%, OR
      = 0.16, 95% CI = 0.12-0.21, P < 10 (-4)), Zhuang (27.8%, OR = 0.73, 95% CI = 0.57
      0.94, P < 0.02) or Meng, Miao, and Hui ethnicity (14.2%, OR = 0.36, 95% CI = 0.29
      0.45, P < 10 (-4)) were less likely than children of Han ethnicity (33.2%) to
      have received a timely birth dose. Children lacking vaccination registration
      cards (OR = 0.64, 95% CI = 0.51-0.80, P < 10 (-4)) and children whose parents or
      guardians did not know the importance of timely HepB immunization (OR = 0.62, 95%
      CI = 0.46-0.84, P < 10 (-2)) were also less likely to have received a timely
      birth dose. Parental knowledge and prioritization of birth-dosing was low among
      children who did not receive it. The timeliness of HepB(1) should improve with
      increasing rates of hospital delivery, training of birth attendants, increasing
      staff and community awareness of the importance of the birth dose, and by
      focusing on vulnerable groups.

PMID- 19861625
TI  - Population seroprevalence of hepatitis E virus antibodies in rural Bangladesh.
AB  - Hepatitis E virus (HEV) causes a substantial burden of sporadic and epidemic
      disease worldwide. HEV infections result in serious morbidity and mortality,
      especially among pregnant women, and have significant economic costs. Few
      population-based studies have characterized the epidemiology of HEV. A rural
      Bangladeshi population was studied to determine the age- and gender- specific
      population seroprevalence of antibodies to HEV. Of 1,134 specimens tested from a
      representative, random population sample, 255 (22.5%) were anti-HEV IgG
      seropositive. Seroprevalence was lower among women (19.7%) than among men
      (25.8%). We found anti-HBc (hepatitis B core) in 380 of 1080(35.2%) tested, anti
      HCV (hepatitis C) in 14 of 917(1.5%) tested, and anti-HAV (hepatitis A) in 116 of
      124(93.5%) tested individuals. Our data suggest that viral hepatitis, especially
      HEV, remains an under-recognized and significant public health problem in rural
      Bangladeshi populations, warranting further attention.

PMID- 19861626
TI  - Household characteristics associated with handwashing with soap in rural
      Bangladesh.
AB  - Handwashing with soap prevents diarrhea and respiratory disease, but it is rarely
      practiced in high-need settings. Among 100 randomly selected villages in rural
      Bangladesh, field workers enrolled 10 households per village and observed and
      recorded household activities for 5 hours. Field workers observed 761 handwashing
      opportunities among household members in 527 households who had just defecated or
      who cleaned a child's anus who had defecated. In the final multivariate analysis,
      having water available at the place to wash hands after toileting (odds ratio =
      2.2, 95% confidence interval 1.3, 4.0) and having soap available at the place to
      wash hands after toileting (odds ratio = 2.1, 95% confidence interval 1.3, 3.4)
      were associated with washing both hands with soap after fecal contact.
      Interventions that improve the presence of water and soap at the designated place
      to wash hands would be expected to improve handwashing behavior and health.

PMID- 19861627
TI  - Persistence of Mycobacterium ulcerans disease (Buruli Ulcer) in the historical
      focus of Kasongo Territory, the Democratic Republic of Congo.
AB  - Fifty years after the last report of Mycobacterium ulcerans infections (Buruli
      ulcer [BU]) in Kasongo Territory, Maniema Province, Democratic Republic of Congo
      (DRC), we conducted a small-scale cross-sectional survey to assess if this
      historical BU focus was still active and if so to explore the disease
      epidemiology. Seventy-five active and inactive BU cases were identified on
      clinical grounds of which two of 28 BU active cases were laboratory confirmed. We
      used a modified BU02 form to reconstruct the local disease dynamics and we
      believe that the horrific conflict in eastern DRC and exceptional flooding were
      the most likely causes of the re-emergence of the disease. There is a need in the
      DRC to decentralize and integrate surveillance and control activities at local
      level to increase the effectiveness of patient management.

PMID- 19861628
TI  - Long-term relapse risk of multibacillary leprosy after completion of 2 years of
      multiple drug therapy (WHO-MDT) in Cebu, Philippines.
AB  - From 1987 to 1994, we enrolled 500 subjects completing 2-year WHO multiple drug
      therapy (MDT) for multibacillary leprosy in a prospective relapse study. Relapse
      was defined as new skin lesions and an increase in the bacterial index (BI) > or
      = 2+ (> or = 100x) at any single slit-skin smear site. At the study end in 2006,
      follow-up was 6,401 subject-years, a mean of 12.8 years/subject. We observed 23
      relapses, 6-16 years after MDT (mean, 10.5 years; 95% confidence interval [CI],
      9.2-11.8), peaking in Years 11-12 (> 1%/year). The cumulative risk was 6.6% (95%
      CI, 5.0-8.2%). In a subset of 181 subjects with pre-MDT average BI > or = 4+, 11
      relapses occurred (cumulative risk, 10.1%). In mouse footpad assays,
      Mycobacterium leprae from relapsed subjects were rifampin and clofazimine
      sensitive. Taken together, the data suggest relapses are related to activation of
      dormant organisms (persisters) not killed by MDT rather than new infection.

PMID- 19861629
TI  - Micro-positron emission tomography in the evaluation of Trypanosoma cruzi-induced
      heart disease: Comparison with other modalities.
AB  - Noninvasive assessment of cardiac structure and function is essential to
      understand the natural course of murine infection with Trypanosoma cruzi.
      Magnetic resonance imaging (MRI) and echocardiography have been used to monitor
      anatomy and function; positron emission tomography (PET) is ideal for monitoring
      metabolic events in the myocardium. Mice infected with T. cruzi (Brazil strain)
      were imaged 15-100 days post infection (dpi). Quantitative (18)F-FDG microPET
      imaging, MRI and echocardiography were performed and compared. Tracer ((18)F-FDG)
      uptake was significantly higher in infected mice at all days of infection, from
      15 to 100 dpi. Dilatation of the right ventricular chamber was observed by MRI
      from 30 to 100 dpi in infected mice. Echocardiography revealed significantly
      reduced ejection fraction by 60 dpi. Combination of these three complementary
      imaging modalities makes it possible to noninvasively quantify cardiovascular
      function, morphology, and metabolism from the earliest days of infection through
      the chronic phase.

PMID- 19861630
TI  - Prevalence of Leptospira spp. in urban rodents from a groceries trade center of
      Medellin, Colombia.
AB  - Leptospirosis is a widely distributed zoonosis, and rats are its most common
      source of infection. Our goal was to determine the frequency for Leptospira
      infection in rodents in a farmers market in the city of Medellin. We performed a
      descriptive transversal study sampling 254 rodents. Rodents were bled and killed,
      and kidneys samples were taken. Supernatants of macerated kidneys were cultured
      on Fletcher medium. Microagglutination tests (MATs) with 11 serovars were also
      carried out in rat serum, and a polymerase chain reaction (PCR) specific for
      pathogenic species was used to test each bacterial culture. All animals were
      identified as Rattus norvegicus; 25% and 20% were positive by MAT and culture,
      respectively. PCR tests of 12 isolates were positive for pathogenic serovars, and
      4 of them were confirmed as L. interrogans by sequencing. These data show the
      role of this natural carrier and shedder of pathogenic leptospires in the
      epidemiology of urban leptospirosis in Colombia.

PMID- 19861631
TI  - Immunologic profiles of persons recruited for a randomized, placebo-controlled
      clinical trial of hookworm infection.
AB  - Data from epidemiologic studies suggest that hookworm infections, in establishing
      an immunologic phenotype conducive to parasite survival, may protect against the
      development of allergic disease. We describe immunologic findings from a clinical
      study designed to investigate the safety of iatrogenic hookworm infection in
      participants with allergic rhinitis. The low, relatively safe level of hookworm
      infection used in this study was immunogenic, inducing eosinophilia and a
      significant specific IgG response. Importantly, no potentiation of IgE responses
      to the environmental allergens to which the participants were sensitized was
      seen. However, no evidence of systemic immune regulation was seen in infected
      participants. This finding may indicate that the level of infection or the
      frequency of infection may have to be altered in future trials to induce a
      therapeutically conducive immunologic phenotype.

PMID- 19861632
TI  - Rapid molecular detection of Opisthorchis viverrini in human fecal samples by
      real-time polymerase chain reaction.
AB  - Real-time fluorescence resonance energy transfer (FRET) polymerase chain reaction
      (PCR) supplemented with melting curve analysis is a highly sensitive and fast
      method offering a high throughput. We report the development of a real-time FRET
      PCR for molecular detection of Opisthorchis viverrini in human fecal samples. The
      diagnostic sensitivity, specificity, accuracy, and positive and negative
      predictive values of this method were 97.5%, 100%, 98.9%, 100%, and 98.2%,
      respectively. The sensitivity was not significantly different from that of the
      quantified formalin-ethyl acetate concentration technique, the gold standard (P >
      0.05). The procedure has potential for diagnosis of human opisthorchiasis in
      disease-endemic areas, for large epidemiologic investigations involving at risk
      populations, and monitoring eradication programs of the liver fluke, which causes
      hepatobiliary diseases and induces cholangiocarcinoma.

PMID- 19861635
TI  - Theta oscillations mediate interaction between prefrontal cortex and medial
      temporal lobe in human memory.
AB  - The medial temporal lobe (MTL) and the prefrontal cortex (PFC) are known to be
      critical structures for human memory processes. Furthermore, it has been
      suggested that they are part of a memory network. Although memory-modulated
      interaction between PFC and MTL has been observed at the hemodynamic level, it
      remains unclear what the neuronal process is that mediates the communication
      between these 2 areas. Experiments in rodents suggest that field oscillations in
      the theta band (4-8 Hz) facilitate PFC-MTL interaction. No such evidence has been
      reported in humans. To address this problem, cortical electrical activity from
      MTL, PFC, and lateral temporal lobe was recorded from implanted electrode grids
      in 3 epilepsy patients performing a verbal free recall task. The data were
      analyzed using a parametric spectral method to obtain estimates of power,
      coherence, and Granger causality. A task-modulated increase in coherence values
      between PFC and MTL was seen during free recall as opposed to a baseline
      condition. Concurrently, the number of coherent PFC-MTL site pairs was
      significantly increased during recall. Granger causality analysis further
      revealed that the increased coherence is a consequence of higher bidirectional
      information flow between the 2 regions, with a generally greater driving from MTL
      to PFC, namely, (MTL-->PFC) > (PFC-->MTL).

PMID- 19861636
TI  - Leading process branch instability in Lis1+/- nonradially migrating interneurons.
AB  - Mammalian forebrain development requires extensive migration, yet the mechanisms
      through which migrating neurons sense and respond to guidance cues are not well
      understood. Similar to the axon growth cone, the leading process and branches of
      neurons may guide migration, but the cytoskeletal events that regulate branching
      are unknown. We have previously shown that loss of microtubule-associated protein
      Lis1 reduces branching during migration compared with wild-type neurons. Using
      time-lapse imaging of Lis1(+/-) and Lis1(+/+) cells migrating from medial
      ganglionic eminence explant cultures, we show that the branching defect is not
      due to a failure to initiate branches but a defect in the stabilization of new
      branches. The leading processes of Lis1(+/-) neurons have reduced expression of
      stabilized, acetylated microtubules compared with Lis1(+/+) neurons. To determine
      whether Lis1 modulates branch stability through its role as the noncatalytic beta
      regulatory subunit of platelet-activating factor (PAF) acetylhydrolase 1b,
      exogenous PAF was applied to wild-type cells. Excess PAF added to wild-type
      neurons phenocopies the branch instability observed in Lis1(+/-) neurons, and a
      PAF antagonist rescues leading process branching in Lis1(+/-) neurons. These data
      highlight a role for Lis1, acting through the PAF pathway, in leading process
      branching and microtubule stabilization.

PMID- 19861637
TI  - Phylogenetic analysis of subgenus vigna species using nuclear ribosomal RNA ITS:
      evidence of hybridization among Vigna unguiculata subspecies.
AB  - Molecular phylogeny among species belonging to subgenus Vigna (genus Vigna) was
      inferred based on internal transcribed spacer (ITS) sequences of 18S-5.8S-26S
      ribosomal RNA gene unit. Analysis showed a total of 356 polymorphic sites of
      which approximately 80% were parsimony informative. Phylogenetic reconstruction
      by neighbor joining and maximum parsimony methods placed the 57 Vigna accessions
      (belonging to 15 species) into 5 major clades. Five species viz. Vigna
      heterophylla, Vigna pubigera, Vigna parkeri, Vigna laurentii, and Vigna gracilis
      whose position in the subgenus was previously not known were placed in the
      section Vigna. A single accession (Vigna unguiculata ssp. tenuis, NI 1637)
      harbored 2 intragenomic ITS variants, indicative of 2 different types of
      ribosomal DNA (rDNA) repeat units. ITS variant type-I was close to ITS from V.
      unguiculata ssp. pubescens, whereas type-II was close to V. unguiculata ssp.
      tenuis. Transcript analysis clearly demonstrates that in accession NI 1637, rDNA
      repeat units with only type-II ITS variants are transcriptionally active.
      Evidence from sequence analysis (of 5.8S, ITS1, and ITS2) and secondary structure
      analysis (of ITS1 and ITS2) indicates that the type-I ITS variant probably does
      not belong to the pseudogenic rDNA repeat units. The results from phylogenetic
      and transcript analysis suggest that the rDNA units with the type-I ITS may have
      introgressed as a result of hybridization (between ssp. tenuis and ssp.
      pubescens); however, it has been epigenetically silenced. The results also
      demonstrate differential evolution of ITS sequence among wild and cultivated
      forms of V. unguiculata.

PMID- 19861638
TI  - Isolation and phylogenetic footprinting analysis of the 5'-regulatory region of
      the floral homeotic gene OrcPI from Orchis italica (Orchidaceae).
AB  - The nucleotide sequences of regulatory elements from homologous genes can be
      strongly divergent. Phylogenetic footprinting, a comparative analysis of
      noncoding regions, can detect putative transcription factor binding sites (TFBSs)
      shared among the regulatory regions of 2 or more homologous genes. These
      conserved motifs have the potential to serve the same regulatory function in
      distantly related taxa. We isolated the 5'-noncoding region of the OrcPI gene, a
      MADS-box transcription factor involved in flower development in Orchis italica,
      using the thermal asymmetric interlaced polymerase chain reaction technique. This
      region (comprising 1352 bp) induced transient beta-glucuronidase expression in
      the petal tissue of white Rosa hybrida flowers and represents the 5'-regulatory
      sequence of the OrcPI gene. Phylogenetic footprinting analysis detected conserved
      regions within the 5'-regulatory sequence of OrcPI and the homologous regions of
      Oryza sativa, Lilium regale, and Arabidopsis thaliana. Some of these sequences
      are known TFBSs described in databases of plant regulatory elements. Nucleotide
      sequence data reported are available in the DDBJ/EMBL/GenBank databases under the
      following accession numbers: AF198055 promoter region of the PISTILLATA (PI) gene
      of A. thaliana; AB094985 cDNA of OrcPI (PI/GLOBOSA [PI/GLO] homologue) of O.
      italica; AB378089 5'-regulatory region of the OrcPI gene of O. italica; AP008211
      putative promoter region of OSMADS2 (PI/GLO homologue) of O. sativa; AP008207
      putative promoter region of OSMADS4 (PI/GLO homologue) of O. sativa; and AB158292
      putative promoter region of the PI/GLO homologue of L. regale.

PMID- 19861639
TI  - Longitudinal analysis of domain-level breast cancer literacy among African
      American women.
AB  - Functional breast cancer literacy was assessed among African-American women and
      measured at the domain level over time. We used the Kin Keeper(SM) Cancer
      Prevention Intervention to educate 161 African-American women on three domains of
      breast cancer literacy: (i) cancer awareness, (ii) knowledge of breast cancer
      screening modalities and (iii) cancer prevention and control. A breast cancer
      literacy assessment was administered pre- and post-educational intervention at
      two time points followed by another assessment 12 months after the second
      intervention. Generalized estimating equations were specified to predict the
      probability of correctly answering questions in each domain over time. Domain
      level literacy differentials exist; at baseline, women had higher test scores in
      the breast cancer prevention and control domain than the cancer awareness domain
      (odds ratio = 1.67, 95% confidence interval 1.19-2.34). After Kin Keeper(SM)
      Cancer Prevention Intervention, African-American women consistently improved
      their breast cancer literacy in all domains over the five time stages (P < 0.001)
      though at different rates for each domain. Differences in domain-level breast
      cancer literacy highlight the importance of assessing literacy at the domain
      level. Interventions to improve African-American women's breast cancer literacy
      should focus on knowledge of breast cancer screening modalities and cancer
      awareness domains.

PMID- 19861640
TI  - Influence of age on clock gene expression in peripheral blood cells of healthy
      women.
AB  - Recent studies have demonstrated a close relationship between circadian clock
      function and the development of obesity and various age-related diseases. In this
      study, we investigated whether messenger RNA (mRNA) levels of clock genes are
      associated with age, body mass index, blood pressures, fasting plasma glucose, or
      shift work. Peripheral blood cells were obtained from 70 healthy women, including
      25 shift workers, at approximately 9:00 AM. Transcript levels of clock genes
      (CLOCK, BMAL1, PER1, and PER3) were determined by real-time quantitative
      polymerase chain reaction. Stepwise multiple regression analysis demonstrated
      that BMAL1 mRNA levels were correlated only with age (beta = -.50, p < .001). In
      contrast, PER3 levels were correlated with fasting plasma glucose (beta = -.29, p
      < .05) and shift work (beta = .31, p < .05). These results suggest that increased
      age, glucose intolerance, and irregular hours independently affect the
      intracellular clock in humans.

PMID- 19861641
TI  - Age differences in energy absorption in the upper extremity during a descent
      movement: implications for arresting a fall.
AB  - BACKGROUND: Falls are the number one cause of unintentional injury in older
      adults. The protective response of "breaking the fall" with the outstretched hand
      is often essential for avoiding injury to the hip and head. In this study, we
      compared the ability of young and older women to absorb the impact energy of a
      fall in the outstretched arms. METHODS: Twenty young (mean age = 21 years) and 20
      older (M = 78 years) women were instructed to slowly lower their body weight,
      similar to the descent phase of a push-up, from body lean angles ranging from 15
      degrees to 90 degrees . Measures were acquired of peak upper extremity energy
      absorption, arm deflection, and hand contact force. RESULTS: On average, older
      women were able to absorb 45% less energy in the dominant arm than young women
      (1.7 +/- 0.5% vs 3.1 +/- 0.4% of their body weight x body height; p < .001).
      These results suggest that, even when both arms participate equally, the average
      energy content of a forward fall exceeds by 5-fold the average energy that our
      older participants could absorb and exceeds by 2.7-fold the average energy that
      young participants could absorb. CONCLUSIONS: During a descent movement that
      simulates fall arrest, the energy-absorbing capacity of the upper extremities in
      older women is nearly half that of young women. Absorbing the full energy of a
      fall in the upper extremities is a challenging task even for healthy young women.
      Strengthening of upper extremity muscles should enhance this ability and
      presumably reduce the risk for injury to the hip and head during a fall.

PMID- 19861643
TI  - An explicit signature of balancing selection for color-vision variation in new
      world monkeys.
AB  - Color vision is an important characteristic of primates and, intriguingly,
      Neotropical monkeys are highly polymorphic for this trait. Recent field studies
      have challenged the conventional view that trichromatic color vision is more
      adaptive than dichromatic color vision. No study has investigated the pattern of
      genetic variation in the long to middle wavelength-sensitive (L-M or red-green)
      opsin gene as compared with that of other genomic regions (neutral references) in
      wild populations of New World monkeys to look for the signature of natural
      selection. Here, we report such a study conducted on spider monkeys and capuchin
      monkeys inhabiting Santa Rosa National Park, Costa Rica. The nucleotide sequence
      of the L-M opsin gene was more polymorphic than the sequences of the neutral
      references, although the opsin-gene sequences were not more divergent between the
      two species than were the sequences of the neutral references. In a coalescence
      simulation that took into account the observed nucleotide diversity of the
      neutral references, the Tajima's D value of the L-M opsin gene deviated
      significantly in a positive direction from the expected range. These results are
      the first to statistically demonstrate balancing selection acting on the
      polymorphic L-M opsin gene of New World monkeys. Taking the results of behavioral
      and genetic studies together, the balancing selection we detected may indicate
      that coexistence of different color-vision types in the same population, also
      characteristic of humans, is adaptive.

PMID- 19861642
TI  - Bacterial genetic signatures of human social phenomena among M. tuberculosis from
      an Aboriginal Canadian population.
AB  - Despite a widespread global distribution and highly variable disease phenotype,
      there is little DNA sequence diversity among isolates of Mycobacterium
      tuberculosis. In addition, many regional population genetic surveys have revealed
      a stereotypical structure in which a single clone, lineage, or clade makes up the
      majority of the population. It is often assumed that dominant clones are highly
      adapted, that is, the overall structure of M. tuberculosis populations is the
      result of positive selection. In order to test this assumption, we analyzed
      genetic data from extant populations of bacteria circulating in Aboriginal
      communities in Saskatchewan, Canada. Demographic parameters of the bacterial
      population were estimated from archival epidemiological data collected over
      approximately 130 years since the onset of epidemic tuberculosis in the host
      communities. Bacterial genetic data were tested against neutral theory
      expectations and the local evolutionary history of M. tuberculosis investigated
      by phylogenetic analysis. Our findings are not consistent with positive selection
      on the bacterial population. Instead, we uncovered founder effects persisting
      over decades and barriers to gene flow within the bacterial population.
      Simulation experiments suggested that a combination of these neutral influences
      could result in the stereotypical structure of M. tuberculosis populations. Some
      aspects of population structure were suggestive of background selection, and data
      were on the whole consistent with combined effects of population bottlenecks,
      subdivision, and background selection. Neutral phenomena, namely, bottlenecks and
      partitions within populations, are prominent influences on the evolution of M.
      tuberculosis and likely contribute to restricted genetic diversity observed
      within this species. Given these influences, a complex evolutionary model will be
      required to define the relative fitness of different M. tuberculosis lineages
      and, ultimately, to uncover the genetic basis for its success as a pathogen.

PMID- 19861644
TI  - Developmental neurotoxicity of pyrethroid insecticides in zebrafish embryos.
AB  - Pyrethroid insecticides are one of the most commonly used residential and
      agricultural insecticides. Based on the increased use of pyrethroids and recent
      studies showing that pregnant women and children are exposed to pyrethroids,
      there are concerns over the potential for developmental neurotoxicity. However,
      there have been relatively few studies on the developmental neurotoxicity of
      pyrethroids. In this study, we sought to investigate the developmental toxicity
      of six common pyrethroids, three type I compounds (permethrin, resmethrin, and
      bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and lambda
      cyhalothrin), and to determine whether zebrafish embryos may be an appropriate
      model for studying the developmental neurotoxicity of pyrethroids. Exposure of
      zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality
      and pericardial edema, with type II compounds being the most potent. At doses
      approaching the LC(50), permethrin and deltamethrin caused craniofacial
      abnormalities. These findings are consistent with mammalian studies demonstrating
      that pyrethroids are mildly teratogenic at very high doses. However, at lower
      doses, body axis curvature and spasms were observed, which were reminiscent of
      the classic syndromes observed with pyrethroid toxicity. Treatment with diazepam
      ameliorated the spasms, while treatment with the sodium channel antagonist MS-222
      ameliorated both spasms and body curvature, suggesting that pyrethroid-induced
      neurotoxicity is similar in zebrafish and mammals. Taken in concert, these data
      suggest that zebrafish may be an appropriate alternative model to study the
      mechanism(s) responsible for the developmental neurotoxicity of pyrethroid
      insecticides and aid in identification of compounds that should be further tested
      in mammalian systems.

PMID- 19861650
TI  - Increasing fish consumption does not affect genotoxicity markers in the colon in
      an intervention study.
AB  - Observational studies suggest that fish consumption is associated with a
      decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could
      reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have
      also been raised over the levels of toxic compounds found in mainly oil-rich
      fish, which could increase genotoxicity. Therefore, the objective was to
      investigate the effects of fish on genotoxicity markers in the colon in a
      randomized controlled parallel intervention study. For a period of 6 months,
      subjects were randomly allocated to receive two extra weekly portions of (i) oil
      rich fish (salmon), (ii) lean fish (cod) or (iii) just dietary advice (DA). The
      Comet Assay was used to measure the DNA damage-inducing potential of fecal water
      (n = 89) and DNA damage in colonocytes (n = 70) collected pre- and post
      intervention as markers of genotoxicity. Genotoxicity of fecal water was not
      markedly changed after fish consumption: 1.0% increase in tail intensity (TI)
      [95% confidence interval (CI) -5.1; 7.0] in the salmon group and 0.4% increase in
      TI (95% CI -5.3; 6.1) in the cod group compared with the DA group. DNA damage in
      colonocytes was also not significantly changed after fish consumption, in either
      the salmon group (-0.5% TI, 95% CI -6.9; 6.0) or cod group (-3.3% TI, 95% CI 
      10.8; 4.3) compared with the DA group. Measurements of genotoxicity of fecal
      water and DNA damage in colonocytes did not correlate (r = 0.06, n = 34). In
      conclusion, increasing consumption of either oil-rich or lean fish did not affect
      genotoxicity markers in the colon.

PMID- 19861649
TI  - Cancer systems biology: a network modeling perspective.
AB  - Cancer is now appreciated as not only a highly heterogenous pathology with
      respect to cell type and tissue origin but also as a disease involving
      dysregulation of multiple pathways governing fundamental cell processes such as
      death, proliferation, differentiation and migration. Thus, the activities of
      molecular networks that execute metabolic or cytoskeletal processes, or regulate
      these by signal transduction, are altered in a complex manner by diverse genetic
      mutations in concert with the environmental context. A major challenge therefore
      is how to develop actionable understanding of this multivariate dysregulation,
      with respect both to how it arises from diverse genetic mutations and to how it
      may be ameliorated by prospective treatments. While high-throughput experimental
      platform technologies ranging from genomic sequencing to transcriptomic,
      proteomic and metabolomic profiling are now commonly used for molecular-level
      characterization of tumor cells and surrounding tissues, the resulting data sets
      defy straightforward intuitive interpretation with respect to potential
      therapeutic targets or the effects of perturbation. In this review article, we
      will discuss how significant advances can be obtained by applying computational
      modeling approaches to elucidate the pathways most critically involved in tumor
      formation and progression, impact of particular mutations on pathway operation,
      consequences of altered cell behavior in tissue environments and effects of
      molecular therapeutics.

PMID- 19861653
TI  - K+ deprivation induces xylem water and K+ transport in sunflower: evidence for a
      co-ordinated control.
AB  - The effect of K+ deprivation on water and K+ transport in roots was studied in
      sunflower plants. Deprivation was achieved in two different ways: by removing K+
      from the growth medium for varying intervals; and by growing plants permanently
      in a low-K+ medium. Removal of K+ from the growth medium for a few hours prompted
      a significant increase in xylem sap exudation, associated with an increase in
      root hydraulic conductivity; however, it did not give rise to any significant
      change in plant K+ content, nor did it favour root K+ exudation. By contrast,
      prolonged K+ deprivation led to a decline in the internal K+ content and
      stimulated water and K+ transport in roots. Leaf application of K+ (Rb+) in
      plants grown permanently in a low-K+ medium inhibited the effect of K+
      deprivation on root water and K+ transport, without significantly modifying the
      internal K+ content of the plants. This treatment had no effect on normal-K+
      plants. These results suggest the existence of mechanisms enabling perception of
      plant K+ status and/or K+ availability in the medium, which trigger transduction
      processes governing the transport of water and K+ from the root to the shoot.

PMID- 19861652
TI  - 1-Aminocyclopropane-1-carboxylic acid (ACC) concentration and ACC synthase
      expression in soybean roots, root tips, and soybean cyst nematode (Heterodera
      glycines)-infected roots.
AB  - Colonization of plant roots by root knot and cyst nematodes requires a functional
      ethylene response pathway. However, ethylene plays many roles in root development
      and whether its role in nematode colonization is direct or indirect, for example
      lateral root initiation or root hair growth, is not known. The temporal
      requirement for ethylene and localized synthesis of ethylene during the life span
      of soybean cyst nematode (SCN) on soybean roots was further investigated.
      Although a significant increase in ethylene evolution was not detected from SCN
      colonized roots, the concentration of the immediate precursor to ethylene, 1
      aminocyclopropane-1-carboxylic acid (ACC), was higher in SCN-colonized root
      pieces and root tips than in other parts of the root. Moreover, expression
      analysis of 17 ACC synthase (ACS) genes indicated that a select set of ACS genes
      is expressed in SCN-colonized root pieces that is clearly different from the set
      of genes expressed in non-colonized roots or root tips. Semi-quantitative real
      time PCR indicated that ACS transcript accumulation correlates with the high
      concentration of ACC in root tips. In addition, an ACS-like sequence was found in
      the public SCN nucleotide database. Acquisition of a full-length sequence for
      this mRNA (accession GQ389647) and alignment with transcripts for other well
      characterized ACS proteins indicated that the nematode sequence is missing a key
      element required for ACS activity and therefore probably is not a functional ACS.
      Moreover, no significant amount of ACC was found in any growth stage of SCN that
      was tested.

PMID- 19861651
TI  - Rosiglitazone prevents the progression of preinvasive lung cancer in a murine
      model.
AB  - There is a critical need to identify efficacious chemopreventive agents for lung
      cancer that can be taken chronically with no side effects and whose mechanisms of
      action do not involve genotoxicity that could drive, rather than impede, cancer
      progression. We evaluated the ability of a chemopreventive cocktail that included
      selenium (antioxidant), rosiglitazone (peroxisome proliferator-activated receptor
      gamma agonist), sodium phenylbutyrate or valproic acid (histone deacetylase
      inhibitors) and hydralazine (cytosine-demethylating agent) to prevent the
      progression of lung cancer in A/J mice treated with NNK. Agents were administered
      alone or in various combinations. Effects of the chemopreventive agents were
      quantified based on the proportion of hyperplasias and adenomas within the mouse
      lung. Significant effects on tumor progression were seen in all treatment groups
      that included rosiglitazone as reflected by a 47-57% increase in number of
      hyperplasias and a 10-30% decrease in adenomas. Cell proliferation was also
      reduced in these treatment groups by approximately 40%. Interestingly, while
      treatment with rosiglitazone alone did not significantly affect lesion size,
      striking effects were seen in the combination therapy group that included sodium
      phenylbutyrate, with the volume of hyperplasias and adenomas decreasing by 40 and
      77%, respectively. These studies demonstrate for the first time that chronic in
      vivo administration of rosiglitazone, used in the management of diabetes
      mellitus, can significantly block the progression of premalignant lung cancer in
      the A/J mouse model.

PMID- 19861654
TI  - Three cotton genes preferentially expressed in flower tissues encode actin
      depolymerizing factors which are involved in F-actin dynamics in cells.
AB  - To investigate whether the high expression levels of actin-depolymerizing factor
      genes are related to pollen development, three GhADF genes (cDNAs) were isolated
      and characterized in cotton. Among them, GhADF6 and GhADF8 were preferentially
      expressed in petals, whereas GhADF7 displayed the highest level of expression in
      anthers, revealing its anther specificity. The GhADF7 transcripts in anthers
      reached its peak value at flowering, suggesting that its expression is
      developmentally-regulated in anthers. The GhADF7 gene including the promoter
      region was isolated from the cotton genome. To demonstrate the specificity of the
      GhADF7 promoter, the 5'-flanking region, including the promoter and 5'
      untranslated region, was fused with the GUS gene. Histochemical assays
      demonstrated that the GhADF7:GUS gene was specifically expressed in pollen
      grains. When pollen grains germinated, very strong GUS staining was detected in
      the elongating pollen tube. Furthermore, overexpression of GhADF7 gene in
      Arabidopsis thaliana reduced the viable pollen grains and, consequently,
      transgenic plants were partially male-sterile. Overexpression of GhADF7 in
      fission yeast (Schizosaccharomyces pombe) altered the balance of actin
      depolymerization and polymerization, leading to the defective cytokinesis and
      multinucleate formation in the cells. Given all the above results together, it is
      proposed that the GhADF7 gene may play an important role in pollen development
      and germination.

PMID- 19861655
TI  - CELL WALL INVERTASE 4 is required for nectar production in Arabidopsis.
AB  - To date, no genes have been reported to directly affect the de novo production of
      floral nectar. In an effort to identify genes involved in nectar production, the
      Affymetrix((R)) ATH1 GeneChip was previously used to examine global gene
      expression profiles in Arabidopsis thaliana nectaries. One of the genes
      displaying highly enriched expression in nectaries was CELL WALL INVERTASE 4
      (AtCWINV4, At2g36190), which encodes an enzyme that putatively catalyses the
      hydrolysis of sucrose into glucose and fructose. RT-PCR was used to confirm the
      nectary-enriched expression of AtCWINV4, as well as an orthologue from Brassica
      rapa. To probe biological function, two independent Arabidopsis cwinv4 T-DNA
      mutants were isolated. Unlike wild-type plants, cwinv4 lines did not produce
      nectar. While overall nectary morphology appeared to be normal, cwinv4 flowers
      accumulated higher than normal levels of starch in the receptacle, but not within
      the nectaries themselves. Conversely, wild-type, but not cwinv4, nectarial
      stomata stained intensely for starch. Cell wall extracts prepared from mutant
      flowers displayed greatly reduced invertase activity when compared with wild-type
      plants, and cwinv4 flowers also accumulated significantly lower levels of total
      soluble sugar. Cumulatively, these results implicate CWINV4 as an absolutely
      required factor for nectar production in the Brassicaceae, specifically by
      maintaining constant sink status within nectaries, thus allowing them to
      accumulate the sugars necessary for nectar production. In addition, CWINV4 is
      probably responsible for the hexose-rich composition observed for many
      Brassicaceae nectars.

PMID- 19861656
TI  - Golgi membrane dynamics after induction of a dominant-negative mutant Sar1 GTPase
      in tobacco.
AB  - An inducible system has been established in Nicotiana tabacum plants allowing
      controlled expression of Sar1-GTP and thus the investigation of protein dynamics
      after inhibition of endoplasmic reticulum (ER) to Golgi transport. Complete Golgi
      disassembly and redistribution of Golgi markers into the ER was observed within
      18-24h after induction. At the ultrastructural level Sar1-GTP expression led to a
      decrease in Golgi stack size followed by Golgi fragmentation and accumulation of
      vesicle remnants. Induction of Sar1-GTP resulted in redistribution of the green
      fluorescent protein (GFP)-tagged Arabidopsis golgins AtCASP and GC1 (golgin
      candidate 1, an Arabidopsis golgin 84 isoform) into the ER or cytoplasm,
      respectively. Additionally, both fusion proteins were observed in punctate
      structures, which co-located with a yellow fluorescent protein (YFP)-tagged
      version of Sar1-GTP. The Sar1-GTP-inducible system is compared with constitutive
      Sar1-GTP expression and brefeldin A treatment, and its potential for the study of
      the composition of ER exit sites and early cis-Golgi structures is discussed.

PMID- 19861657
TI  - Constitutive water-conserving mechanisms are correlated with the terminal drought
      tolerance of pearl millet [Pennisetum glaucum (L.) R. Br.].
AB  - Pearl millet, a key staple crop of the semi-arid tropics, is mostly grown in
      water-limited conditions, and improving its performance depends on how genotypes
      manage limited water resources. This study investigates whether the control of
      water loss under non-limiting water conditions is involved in the terminal
      drought tolerance of pearl millet. Two pairs of tolerant x sensitive pearl millet
      genotypes, PRLT 2/89-33-H77/833-2 and 863B-P2-ICMB 841-P3, and near-isogenic
      lines (NILs), introgressed with a terminal drought tolerance quantitative trait
      locus (QTL) from the donor parent PRLT 2/89-33 into H77/833-2 (NILs-QTL), were
      tested. Upon exposure to water deficit, transpiration began to decline at lower
      fractions of transpirable soil water (FTSW) in tolerant than in sensitive
      genotypes, and NILs-QTL followed the pattern of the tolerant parents. The
      transpiration rate (Tr, in g water loss cm(-2) d(-1)) under well-watered
      conditions was lower in tolerant than in sensitive parental genotypes, and the Tr
      of NILs-QTL followed the pattern of the tolerant parents. In addition, Tr
      measured in detached leaves (g water loss cm(-2) h(-1)) from field-grown plants
      of the parental lines showed lower Tr values in tolerant parents. Defoliation led
      to an increase in Tr that was higher in sensitive than in tolerant genotypes. The
      differences in Tr between genotypes was not related to the stomatal density.
      These results demonstrate that constitutive traits controlling leaf water loss
      under well-watered conditions correlate with the terminal drought tolerance of
      pearl millet. Such traits may lead to more water being available for grain
      filling under terminal drought.

PMID- 19861659
TI  - The cover. Giant Indian fruit bat.

PMID- 19861658
TI  - Effects of peripheral arterial disease on outcomes in advanced chronic systolic
      heart failure: a propensity-matched study.
AB  - BACKGROUND: The effect of peripheral arterial disease (PAD) on outcomes in
      patients with chronic heart failure (HF) has not been examined in propensity
      matched studies. METHODS AND RESULTS: Of the 2689 patients with advanced chronic
      systolic HF in the Beta-Blocker Evaluation of Survival Trial, 441 had a history
      of PAD. Propensity scores for a history of PAD, calculated for each patient using
      a multivariable logistic regression model, were used to assemble a matched cohort
      of 299 and 1015 patients, respectively, with and without PAD who were well
      balanced on 65 measured baseline characteristics. Cox regression models were used
      to estimate hazard ratios and 95% CIs for associations between PAD and outcomes
      during 4.1 years of follow-up. Patients had a mean age of 63+/-11 years, 19% were
      women, and 19% were black. All-cause mortality occurred in 43% and 33% of
      patients with and without a history of PAD, respectively (hazard ratio when PAD
      was compared with no history of PAD, 1.40; 95% CI, 1.14 to 1.72; P=0.001). All
      cause hospitalization occurred in 75% and 63% of patients with and without PAD,
      respectively (hazard ratio when PAD was compared with no history of PAD, 1.36;
      95% CI, 1.16 to 1.58; P<0.0001). PAD-associated hazard ratios for cardiovascular
      mortality, HF mortality, and HF hospitalization were 1.31 (95% CI, 1.04 to 1.63;
      P=0.019), 1.40 (95% CI, 0.97 to 2.02; P=0.076), and 1.05 (95% CI, 0.86 to 1.29;
      P=0.635), respectively. CONCLUSIONS: In a well-balanced propensity-matched
      population of chronic systolic HF patients, a history of PAD was independently
      associated with increased mortality and hospitalization.

PMID- 19861660
TI  - A piece of my mind. A gift of time.

PMID- 19861661
TI  - FDA steps up efforts to find, remove violators of clinical trial regulations.

PMID- 19861662
TI  - AHA: added sugar not so sweet.

PMID- 19861663
TI  - Obesity and survival among patients with pancreatic cancer.

PMID- 19861664
TI  - Radiation dose-reduction program for cardiac computed tomography angiography.

PMID- 19861665
TI  - Tuberculosis and the inflammatory processes of obesity in human evolution.

PMID- 19861666
TI  - Cost-related medication nonadherence after implementation of Medicare Part D,
      2006-2007.

PMID- 19861667
TI  - Comparison of liquid-based cytology with conventional cytology for detection of
      cervical cancer precursors: a randomized controlled trial.
AB  - CONTEXT: Liquid-based cytology has been developed as an alternative for
      conventional cervical cytology. Despite numerous studies and systematic reviews,
      controversy remains about its diagnostic accuracy. OBJECTIVE: To assess the
      performance of liquid-based cytology compared with conventional cytology in terms
      of detection of histologically confirmed cervical intraepithelial neoplasia
      (CIN). DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized controlled trial
      involving 89,784 women aged 30 to 60 years participating in the Dutch cervical
      screening program at 246 family practices. One hundred twenty-two practices were
      assigned to use liquid-based cytology and screened 49,222 patients and 124
      practices were assigned to use the conventional Papanicolaou (Pap) test and
      screened 40,562 patients between April 2004 and July 1, 2006. Patients were
      followed up for 18 months through January 31, 2008. INTERVENTION: Screening for
      CIN using liquid-based cytology or conventional papanicolaou (Pap) test and the
      blinded review of all follow-up of screen-positive women (blinded to the type of
      cytology and the initial result). MAIN OUTCOME MEASURES: Intention-to-treat and
      per-protocol analysis of the detection rates of and positive predictive values
      for histologically verified CIN in both cytology systems. Outcomes are presented
      as crude and adjusted rate ratios (adjustment for age, urbanization, study site,
      and period). RESULTS: The adjusted detection rate ratios for CIN grade 1+ was
      1.01 (95% confidence interval [CI], 0.85-1.19); for CIN grade 2+, 1.00 (95% CI,
      0.84-1.20); for CIN grade 3+, 1.05 (95% CI, 0.86-1.29); and for carcinoma, 1.69
      (95% CI, 0.96-2.99). The adjusted positive predictive value (PPV) ratios,
      considered at several cytological cutoffs and for various outcomes of CIN did not
      differ significantly from unity. CONCLUSION: This study indicates that liquid
      based cytology does not perform better than conventional Pap tests in terms of
      relative sensitivity and PPV for detection of cervical cancer precursors. TRIAL
      REGISTRATION: trialregister.nl Identifier: NTR1032.

PMID- 19861668
TI  - Cardiometabolic risk of second-generation antipsychotic medications during first
      time use in children and adolescents.
AB  - CONTEXT: Cardiometabolic effects of second-generation antipsychotic medications
      are concerning but have not been sufficiently studied in pediatric and adolescent
      patients naive to antipsychotic medication. OBJECTIVE: To study the association
      of second-generation antipsychotic medications with body composition and
      metabolic parameters in patients without prior antipsychotic medication exposure.
      DESIGN, SETTING, AND PATIENTS: Nonrandomized Second-Generation Antipsychotic
      Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort
      study, conducted between December 2001 and September 2007 at semi-urban, tertiary
      care, academic inpatient and outpatient clinics in Queens, New York, with a
      catchment area of 4.5-million individuals. Of 505 youth aged 4 to 19 years with 1
      week or less of antipsychotic medication exposure, 338 were enrolled (66.9%). Of
      these patients, 272 had at least 1 postbaseline assessment (80.5%), and 205
      patients [corrected] completed the study (60.7%). Patients had mood spectrum (n =
      130; 47.8%), schizophrenia spectrum (n = 82; 30.1%), and disruptive or aggressive
      behavior spectrum (n = 60; 22.1%) disorders. Fifteen patients who refused
      participation or were nonadherent served as a comparison group. INTERVENTION:
      Treatment with aripiprazole, olanzapine, quetiapine, or risperidone for 12 weeks.
      MAIN OUTCOME MEASURES: Weight gain and changes in lipid and metabolic parameters.
      RESULTS: After a median of 10.8 weeks (interquartile range, 10.5-11.2 weeks) of
      treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7
      kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine
      (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by
      4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the
      minimal weight change of 0.2 kg (95% CI, -1.0 to 1.4 kg) in the untreated
      comparison group (n = 15). With olanzapine and quetiapine, respectively, mean
      levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to
      24.3 mg/dL] P < .001 and 9.1 mg/dL [95% CI, 0.4 to 17.7 mg/dL] P = .046),
      triglycerides (24.3 mg/dL [95% CI, 9.8 to 38.9 mg/dL] P = .002 and 37.0 mg/dL
      [95% CI, 10.1 to 63.8 mg/dL] P = .01), non-high-density lipoprotein (HDL)
      cholesterol (16.8 mg/dL [95% CI, 9.3 to 24.3 mg/dL] P < .001 and 9.9 mg/dL [95%
      CI, 1.4 to 18.4 mg/dL] P = .03), and ratio of triglycerides to HDL cholesterol
      (0.6 [95% CI, 0.2 to 0.9] P = .002 and (1.2 [95% CI, 0.4 to 2.0] P = .004). With
      risperidone, triglycerides increased significantly (mean level, 9.7 mg/dL [95%
      CI, 0.5 to 19.0 mg/dL]; P = .04). Metabolic baseline-to-end-point changes were
      not significant with aripiprazole or in the untreated comparison group.
      CONCLUSIONS: First-time second-generation antipsychotic medication use was
      associated with significant weight gain with each medication. Metabolic changes
      varied among the 4 antipsychotic medications.

PMID- 19861669
TI  - Geographic access to burn center hospitals.
AB  - CONTEXT: The delivery of burn care is a resource-intensive endeavor that requires
      specialized personnel and equipment. The optimal geographic distribution of burn
      centers has long been debated; however, the current distribution of centers
      relative to geographic area and population is unknown. OBJECTIVE: To estimate the
      proportion of the US population living within 1 and 2 hours by rotary air
      transport (helicopter) or ground transport of a burn care facility. DESIGN AND
      SETTING: A cross-sectional analysis of geographic access to US burn centers
      utilizing the 2000 US census, road and speed limit data, the Atlas and Database
      of Air Medical Services database, and the 2008 American Burn Association
      Directory. MAIN OUTCOME MEASURE: The proportion of state, regional, and national
      population living within 1 and 2 hours by air transport or ground transport of a
      burn care facility. RESULTS: In 2008, there were 128 self-reported burn centers
      in the United States including 51 American Burn Association-verified centers. An
      estimated 25.1% and 46.3% of the US population live within 1 and 2 hours by
      ground transport, respectively, of a verified burn center. By air, 53.9% and
      79.0% of the population live within 1 and 2 hours, respectively, of a verified
      center. There was significant regional variation in access to verified burn
      centers by both ground and rotary air transport. The greatest proportion of the
      population with access was highest in the northeast region and lowest in the
      southern United States. CONCLUSION: Nearly 80% of the US population lives within
      2 hours by ground or rotary air transport of a verified burn center; however,
      there is both state and regional variation in geographic access to these centers.

PMID- 19861670
TI  - Cardiovascular and noncardiovascular mortality among patients starting dialysis.
AB  - CONTEXT: Cardiovascular mortality is considered the main cause of death in
      patients receiving dialysis and is 10 to 20 times higher in such patients than in
      the general population. OBJECTIVE: To evaluate if high overall mortality in
      patients starting dialysis is a consequence of increased cardiovascular mortality
      risk only or whether noncardiovascular mortality is equally increased. DESIGN,
      SETTING, AND PATIENTS: Using data from between January 1, 1994, and January 1,
      2007, age-stratified mortality in a European cohort of adults starting dialysis
      and receiving follow-up for a mean of 1.8 (SD, 1.1) years (European Renal
      Association-European Dialysis and Transplant Association [ERA-EDTA] Registry [N =
      123,407]) was compared with the European general population (Eurostat). MAIN
      OUTCOME MEASURES: Cause of death was recorded by ERA-EDTA codes in patients and
      matching International Statistical Classification of Diseases, 10th Revision
      codes in the general population. Standardized cardiovascular and
      noncardiovascular mortality rates, their ratio, difference, and relative excess
      of cardiovascular over noncardiovascular mortality were calculated. RESULTS:
      Overall all-cause mortality rates in patients and the general population were 192
      per 1000 person-years (95% confidence interval [CI], 190-193) and 12.055 per 1000
      person-years (95% CI, 12.05-12.06), respectively. Cause of death was known for
      90% of the patients and 99% of the general population. In patients, 16,654 deaths
      (39%) were cardiovascular and 21,654 (51%) were noncardiovascular. In the general
      population, 7,041,747 deaths (40%) were cardiovascular and 10,183,322 (58%) were
      noncardiovascular. Cardiovascular and noncardiovascular mortality rates in
      patients were respectively 38.1 per 1000 person-years (95% CI, 37.2-39.0) and
      50.1 per 1000 person-years (95% CI, 48.9-51.2) higher than in the general
      population. On a relative scale, standardized cardiovascular and
      noncardiovascular mortality were respectively 8.8 (95% CI, 8.6-9.0) and 8.1 (95%
      CI, 7.9-8.3) times higher than in the general population. The ratio of these
      rates, ie, relative excess of cardiovascular over noncardiovascular mortality in
      patients starting dialysis compared with the general population, was 1.09 (95%
      CI, 1.06-1.12). Relative excess in a sensitivity analysis in which
      unknown/missing causes of death were regarded either as noncardiovascular or
      cardiovascular varied between 0.90 (95% CI, 0.88-0.93) and 1.39 (95% CI, 1.35
      1.43). CONCLUSION: Patients starting dialysis have a generally increased risk of
      death that is not specifically caused by excess cardiovascular mortality.

PMID- 19861671
TI  - Risk of pancreatic cancer in families with Lynch syndrome.
AB  - CONTEXT: Lynch syndrome is an inherited cause of colorectal cancer caused by
      mutations of DNA mismatch repair (MMR) genes. A number of extracolonic tumors
      have been associated with the disorder, including pancreatic cancer; however, the
      risk of pancreatic cancer in Lynch syndrome is uncertain and not quantified.
      OBJECTIVE: To estimate pancreatic cancer risk in families with germline MMR gene
      mutations. DESIGN, SETTING, AND PATIENTS: Cancer histories of probands and their
      relatives were evaluated in MMR gene mutation carriers in the familial cancer
      registries of the Dana-Farber Cancer Institute (n = 80), Boston, Massachusetts,
      and University of Michigan Comprehensive Cancer Center (n = 67), Ann Arbor,
      Michigan. Families enrolled before the study start date (June 2008) were
      eligible. Age-specific cumulative risks and hazard ratio estimates of pancreatic
      cancer risk were calculated and compared with the general population using
      modified segregation analysis, with correction for ascertainment. MAIN OUTCOME
      MEASURES: Age-specific cumulative risks and hazard ratio estimates of pancreatic
      cancer risk. RESULTS: Data on 6342 individuals from 147 families with MMR gene
      mutations were analyzed. Thirty-one families (21.1%) reported at least 1 case of
      pancreatic cancer. Forty-seven pancreatic cancers were reported (21 men and 26
      women), with no sex-related difference in age of diagnosis (51.5 vs 56.5 years
      for men and women, respectively). The cumulative risk of pancreatic cancer in
      these families with gene mutations was 1.31% (95% confidence interval [CI], 0.31%
      2.32%) up to age 50 years and 3.68% (95% CI, 1.45%-5.88%) up to age 70 years,
      which represents an 8.6-fold increase (95% CI, 4.7-15.7) compared with the
      general population. CONCLUSIONS: Among 147 families with germline MMR gene
      mutations, the risk of pancreatic cancer was increased compared with the US
      population. Individuals with MMR gene mutations and a family history of
      pancreatic cancer are appropriate to include in studies to further define the
      risk of premalignant and malignant pancreatic neoplasms and potential benefits
      and limitations of surveillance.

PMID- 19861673
TI  - Health care choices and decisions in the United States and Canada.

PMID- 19861672
TI  - DNA beta-amyloid(1-42) trimer immunization for Alzheimer disease in a wild-type
      mouse model.
AB  - CONTEXT: DNA beta-amyloid(1-42) (Abeta42) trimer immunization was developed to
      produce specific T helper 2 cell (T(H)2)-type antibodies to provide an effective
      and safe therapy for Alzheimer disease (AD) by reducing elevated levels of
      Abeta42 peptide that occur in the brain of patients with AD. OBJECTIVE: To
      compare the immune response in wild-type mice after immunization with DNA Abeta42
      trimer and Abeta42 peptide. DESIGN AND INTERVENTION: Wild-type mice received
      either 4 microg of DNA Abeta42 trimer immunization administered with gene gun (n
      = 8) or intraperitoneal injection of 100 microg of human Abeta42 peptide with the
      adjuvant Quil A (n = 8). Titers, epitope mapping, and isotypes of the Abeta42
      specific antibodies were analyzed. MAIN OUTCOME MEASURES: Antibody titers,
      mapping of binding sites (epitopes), isotype profiles of the Abeta42-specific
      antibodies, and T-cell activation. RESULTS: DNA Abeta42 trimer immunization
      resulted in antibody titers with a mean of 15 microg per milliliter of plasma.
      The isotype profile of the antibodies differed markedly. A predominant IgG1
      antibody response was found in the DNA-immunized mice, indicating a T(H)2 type of
      immune response (IgG1/IgG2a ratio of 10). The peptide-immunized mice showed a
      mixed T(H)1/T(H)2 immune response (IgG1/IgG2a ratio of 1) (P < .001). No
      increased T-cell proliferation was observed in the DNA-immunized mice (P = .03).
      CONCLUSION: In this preliminary study in a wild-type mouse model, DNA Abeta42
      trimer immunization protocol produced a T(H)2 immune response and appeared to
      have low potential to cause an inflammatory T-cell response.

PMID- 19861674
TI  - Patient-centered care and preference-sensitive decision making.

PMID- 19861675
TI  - Reform of continuing medical education: investments in physician human capital.

PMID- 19861676
TI  - Screening and prevention methods for cervical cancer.

PMID- 19861677
TI  - Implications of marked weight gain associated with atypical antipsychotic
      medications in children and adolescents.

PMID- 19861678
TI  - JAMA patient page. Burn injuries.

PMID- 19861680
TI  - The small 11 kDa nonstructural protein of human parvovirus B19 plays a key role
      in inducing apoptosis during B19 virus infection of primary erythroid progenitor
      cells.
AB  - Human parvovirus B19 (B19V) infection shows a strong erythroid tropism and
      drastically destroys erythroid progenitor cells, thus leading to most of the
      disease outcomes associated with B19V infection. In this study, we systematically
      examined the 3 B19V nonstructural proteins, 7.5 kDa, 11 kDa, and NS1, for their
      function in inducing apoptosis in transfection of primary ex vivo-expanded
      erythroid progenitor cells, in comparison with apoptosis induced during B19V
      infection. Our results show that 11 kDa is a more significant inducer of
      apoptosis than NS1, whereas 7.5 kDa does not induce apoptosis. Furthermore, we
      determined that caspase-10, an initiator caspase in death receptor signaling, is
      the most active caspase in apoptotic erythroid progenitors induced by 11 kDa and
      NS1 as well as during B19V infection. More importantly, cytoplasm-localized 11
      kDa is expressed at least 100 times more than nucleus-localized NS1 at the
      protein level in primary erythroid progenitor cells infected with B19V; and
      inhibition of 11 kDa expression using antisense oligos targeting specifically to
      the 11 kDa-encoding mRNAs reduces apoptosis significantly during B19V infection
      of erythroid progenitor cells. Taken together, these results demonstrate that the
      11 kDa protein contributes to erythroid progenitor cell death during B19V
      infection.

PMID- 19861679
TI  - Loss-of-function Additional sex combs like 1 mutations disrupt hematopoiesis but
      do not cause severe myelodysplasia or leukemia.
AB  - The Additional sex combs like 1 (Asxl1) gene is 1 of 3 mammalian homologs of the
      Additional sex combs (Asx) gene of Drosophila. Asx is unusual because it is
      required to maintain both activation and silencing of Hox genes in flies and
      mice. Asxl proteins are characterized by an amino terminal homology domain, by
      interaction domains for nuclear receptors, and by a C-terminal plant homeodomain
      protein-protein interaction domain. A recent study of patients with
      myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML)
      revealed a high incidence of truncation mutations that would delete the PHD
      domain of ASXL1. Here, we show that Asxl1 is expressed in all hematopoietic cell
      fractions analyzed. Asxl1 knockout mice exhibit defects in frequency of
      differentiation of lymphoid and myeloid progenitors, but not in multipotent
      progenitors. We do not detect effects on hematopoietic stem cells, or in
      peripheral blood. Notably, we do not detect severe myelodysplastic phenotypes or
      leukemia in this loss-of-function model. We conclude that Asxl1 is needed for
      normal hematopoiesis. The mild phenotypes observed may be because other Asxl
      genes have redundant function with Asxl1, or alternatively, MDS or oncogenic
      phenotypes may result from gain-of-function Asxl mutations caused by genomic
      amplification, gene fusion, or truncation of Asxl1.

PMID- 19861681
TI  - Residual platelet factor V ensures thrombin generation in patients with severe
      congenital factor V deficiency and mild bleeding symptoms.
AB  - Coagulation factor V (FV), present in plasma and platelets, is indispensable to
      thrombin formation, yet patients with undetectable plasma FV seldom experience
      major bleeding. We used thrombin generation assays to explore the role of
      platelet FV in 4 patients with severe congenital FV deficiency (3 with plasma FV
      clotting activity [FV:C] < 1%). When triggered with tissue factor (TF)
      concentrations up to 50pM, platelet-poor plasma (PPP) from the patients with
      undetectable plasma FV showed no thrombin generation, whereas platelet-rich
      plasma (PRP) formed thrombin already at 1 to 5pM of TF. Thrombin generation in
      PRP from the FV-deficient patients was enhanced to near-normal levels by platelet
      activators (collagen or Ca(2+)-ionophore) and could be completely suppressed by
      specific FV inhibitors, suggesting FV dependence. Accordingly, platelet FV
      antigen and activity were measurable in all FV-deficient patients and platelet
      FVa could be visualized by Western blotting. Normalization of the tissue factor
      pathway inhibitor (TFPI) level, which is physiologically low in FV-deficient
      plasma, almost completely abolished thrombin generation in PRP from the FV
      deficient patients. In conclusion, patients with undetectable plasma FV may
      contain functional FV in their platelets. In combination with low TFPI level,
      residual platelet FV allows sufficient thrombin generation to rescue these
      patients from fatal bleeding.

PMID- 19861682
TI  - Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its
      substrate.
AB  - Leukocytes migrate from the blood into areas of inflammation by interacting with
      various adhesion molecules on endothelial cells. Vascular adhesion protein-1 (VAP
      1) is a glycoprotein expressed on inflamed endothelium where it plays a dual
      role: it is both an enzyme that oxidizes primary amines and an adhesin that is
      involved in leukocyte trafficking to sites of inflammation. Although VAP-1 was
      identified more than 15 years ago, the counterreceptor(s) for VAP-1 on leukocytes
      has remained unknown. Here we have identified Siglec-10 as a leukocyte ligand for
      VAP-1 using phage display screenings. The binding between Siglec-10 and VAP-1 was
      verified by different adhesion assays, and this interaction was also consistent
      with molecular modeling. Moreover, the interaction between Siglec-10 and VAP-1
      led to increased hydrogen peroxide production, indicating that Siglec-10 serves
      as a substrate for VAP-1. Thus, the Siglec-10-VAP-1 interaction seems to mediate
      lymphocyte adhesion to endothelium and has the potential to modify the
      inflammatory microenvironment via the enzymatic end products.

PMID- 19861683
TI  - How I treat multiple myeloma in younger patients.
AB  - Therapeutic options for multiple myeloma (MM) patients have changed quickly in
      recent years and uncertainty has arisen about optimal approaches to therapy. A
      reasonable goal of MM treatment in younger "transplant eligible" patients is to
      initiate therapy with a target goal of durable complete remission, and the
      anticipated consequence of long-term disease control. [corrected] To achieve this
      goal we recommend induction therapy with multi-agent combination chemotherapies
      (usually selected from bortezomib, lenalidomide, thalidomide, cyclophosphamide,
      and corticosteriods) which when employed together elicit frequent, rapid, and
      deep responses. We recommend consolidation with high-dose melphalan and
      autologous stem cell transplantation in the majority of patients willing and able
      to undergo this procedure and subsequent maintenance therapy in those failing to
      achieve a complete response or at high risk for early relapse based on
      prognostic, genetically defined risk factors. Defining genetic risk for early
      relapse is therefore an important aspect of early diagnostic testing and
      attention to minimizing expected toxicities once therapy begins is critical in
      ensuring the efficacy of modern combination therapy approaches. When access to
      newer drugs is restricted participation in clinical trials should be pursued.

PMID- 19861684
TI  - Hes1 immortalizes committed progenitors and plays a role in blast crisis
      transition in chronic myelogenous leukemia.
AB  - Hairy enhancer of split 1 (Hes1) is a basic helix-loop-helix transcriptional
      repressor that affects differentiation and often helps maintain cells in an
      immature state in various tissues. Here we show that retroviral expression of
      Hes1 immortalizes common myeloid progenitors (CMPs) and granulocyte-macrophage
      progenitors (GMPs) in the presence of interleukin-3, conferring permanent
      replating capability on these cells. Whereas these cells did not develop
      myeloproliferative neoplasms when intravenously administered to irradiated mice,
      the combination of Hes1 and BCR-ABL in CMPs and GMPs caused acute leukemia
      resembling blast crisis of chronic myelogenous leukemia (CML), resulting in rapid
      death of the recipient mice. On the other hand, BCR-ABL alone caused CML-like
      disease when expressed in c-Kit-positive, Sca-1-positive, and lineage-negative
      hematopoietic stem cells (KSLs), but not committed progenitors CMPs or GMPs, as
      previously reported. Leukemic cells derived from Hes1 and BCR-ABL-expressing CMPs
      and GMPs were more immature than those derived from BCR-ABL-expressing KSLs.
      Intriguingly, Hes1 was highly expressed in 8 of 20 patients with CML in blast
      crisis, but not in the chronic phase, and dominant negative Hes1 retarded the
      growth of some CML cell lines expressing Hes1. These results suggest that Hes1 is
      a key molecule in blast crisis transition in CML.

PMID- 19861685
TI  - Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and
      with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic
      uremic syndrome.
AB  - Factor H autoantibodies have been reported in approximately 10% of patients with
      atypical hemolytic uremic syndrome (aHUS) and are associated with deficiency of
      factor H-related proteins 1 and 3. In this study we examined the prevalence of
      factor H autoantibodies in the Newcastle cohort of aHUS patients, determined
      whether the presence of such autoantibodies is always associated with deficiency
      of factor H-related proteins 1 and 3, and examined whether such patients have
      additional susceptibility factors and/or mutations in the genes encoding
      complement regulator/activators. We screened 142 patients with aHUS and found
      factor H autoantibodies in 13 individuals (age 1-11 years). The presence of the
      autoantibodies was confirmed by Western blotting. By using multiplex ligation
      dependent probe amplification we measured complement factor H-related (CFHR)1 and
      CFHR3 copy number. In 10 of the 13 patients there were 0 copies of CFHR1, and in
      3 patients there were 2. In 3 of the patients with 0 copies of CFHR1 there was 1
      copy of CFHR3, and these individuals exhibited a novel deletion incorporating
      CFHR1 and CFHR4. In 5 patients mutations were identified: 1 in CFH, 1 in CFI, 1
      in CD46, and 2 in C3. The latter observation emphasizes that multiple concurrent
      factors may be necessary in individual patients for disease manifestation.

PMID- 19861687
TI  - Confronting morphogen gradients: how important are they for growth?
AB  - Morphogens are crucial for regulating the patterning and the growth of organs. In
      the developing fly wing, graded distributions of the morphogens Decapentaplegic
      and Wingless are essential for tissue patterning, but when it comes to growth,
      evidence suggests that it may not be so.

PMID- 19861688
TI  - P-REX2a driving tumorigenesis by PTEN inhibition.
AB  - The phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10)
      antagonizes phosphoinositide 3-kinase (PI3K) signaling and is one of the most
      frequently mutated tumor suppressors in human cancers. Its regulation appears
      complex and is of great potential clinical importance. The protein P-REX2a
      (phosphatidylinositol 3,4,5-trisphosphate Rac exchanger 2a), better known as a
      regulator of the small guanosine triphosphatase Rac, has been identified as a
      direct regulator of PTEN activity and as a potential oncoprotein. P-REX2a can
      stimulate cell proliferation by inhibiting PTEN and stimulating downstream PI3K
      dependent signaling. This suggests that aberrant control of PTEN by P-REX2a may
      represent a key tumorigenic mechanism, in agreement with recent studies
      supporting the pathological relevance of several other proposed PTEN regulators.

PMID- 19861689
TI  - An atypical CNG channel activated by a single cGMP molecule controls sperm
      chemotaxis.
AB  - Sperm of the sea urchin Arbacia punctulata can respond to a single molecule of
      chemoattractant released by an egg. The mechanism underlying this extreme
      sensitivity is unknown. Crucial signaling events in the response of A. punctulata
      sperm to chemoattractant include the rapid synthesis of the intracellular
      messenger guanosine 3',5'-monophosphate (cGMP) and the ensuing membrane
      hyperpolarization that results from the opening of potassium-selective cyclic
      nucleotide-gated (CNGK) channels. Here, we use calibrated photolysis of caged
      cGMP to show that approximately 45 cGMP molecules are generated during the
      response to a single molecule of chemoattractant. The CNGK channel can respond to
      such small cGMP changes because it is exquisitely sensitive to cGMP and activated
      in a noncooperative fashion. Like voltage-activated Ca(v) and Na(v) channels, the
      CNGK polypeptide consists of four homologous repeat sequences. Disabling each of
      the four cyclic nucleotide-binding sites through mutagenesis revealed that
      binding of a single cGMP molecule to repeat 3 is necessary and sufficient to
      activate the CNGK channel. Thus, CNGK has developed a mechanism of activation
      that is different from the activation of other CNG channels, which requires the
      cooperative binding of several ligands and operates in the micromolar rather than
      the nanomolar range.

PMID- 19861691
TI  - To co-author or not to co-author: how to write, publish, and negotiate issues of
      authorship with undergraduate research students.
AB  - This Teaching Resource emphasizes the value of publishing with undergraduates and
      may be particularly helpful to incoming faculty who are new to the process of
      working with students. Beyond simply extolling the virtues of undergraduate
      research, we examine how such deep learning experiences for students can
      translate into unique opportunities for the faculty to demonstrate devotion to
      both teaching and scholarship. Along with highlighting the reasons faculty should
      consider publishing with undergraduates, we identify the particular challenges
      that accompany this suggestion and discuss strategies for overcoming them. Our
      resource includes two decision trees for helping faculty determine whether
      publishing with undergraduates represents a reasonable and attainable goal and
      whether an undergraduate has earned authorship. Based on our experience at
      primarily undergraduate institutions, we provide a list of strategies that may
      facilitate writing with undergraduates and lead to certain milestones in the
      careers of both students and faculty.

PMID- 19861690
TI  - Increased MKK4 abundance with replicative senescence is linked to the joint
      reduction of multiple microRNAs.
AB  - MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator
      of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4
      increases in senescent human diploid fibroblasts through enhanced translation. We
      identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target the
      MKK4 messenger RNA (mRNA); the abundance of these microRNAs decreased during
      replicative senescence. Individually modulating the amount of each microRNA did
      not modify MKK4 abundance, but their concomitant overexpression decreased and
      their joint reduction increased MKK4 abundance. Reporter analyses indicated that
      these microRNAs acted through the MKK4 5' and 3' untranslated regions. Elevated
      MKK4 abundance inhibited cell proliferation and increased the phosphorylation and
      activity of p38 and PRAK (p38-regulated/activated protein kinase). Thus, multiple
      microRNAs acting on a single target, the MKK4 mRNA, collectively influence MKK4
      abundance during replicative senescence.

PMID- 19861692
TI  - Inhibition of enzymatic degradation of adhesive-dentin interfaces.
AB  - Adhesive procedures activate dentin-associated matrix metalloproteinases (MMPs),
      and so iatrogenically initiate bond degradation. We hypothesized that adding MMP
      inhibitors to adhesive primers may prevent this endogenous enzymatic degradation,
      thereby improving bond durability. A non-specific MMP inhibitor (chlorhexidine)
      and a MMP-2/9-specific inhibitor (SB-3CT) were admixed to the primers of an etch
      & rinse and a self-etch adhesive, both considered as gold-standard adhesives
      within their respective categories. For dentin powder exposed to the adhesives
      under clinical application conditions, gelatin zymography revealed the release of
      MMP-2 (not of MMP-9) by the etch & rinse adhesive, while no release of enzymes
      could be detected for the mild self-etch adhesive, most likely because of its
      limited dentin demineralization effect. The built-in MMP inhibitors appeared
      effective in reducing bond degradation only for the etch & rinse adhesive, and
      not for the self-etch adhesive. Water sorption of adhesive interfaces most likely
      remains the principal mechanism of bond degradation, while endogenous enzymes
      appear to contribute to bond degradation of only etch & rinse adhesives.

PMID- 19861694
TI  - Physical activity levels after characterized chondrocyte implantation versus
      microfracture in the knee and the relationship to objective functional outcome
      with 2-year follow-up.
AB  - BACKGROUND: Characterized chondrocyte implantation results in superior structural
      repair compared with microfracture, but may be associated with a slower recovery
      of physical activity levels due to the arthrotomy. HYPOTHESES: Our hypotheses
      were that (1) microfracture results in increased activity levels over 2 years
      after surgery compared with characterized chondrocyte implantation, (2) patients
      with high preinjury activity levels have a better functional outcome, and (3)
      high levels of low-load activities after surgery improve functional outcome.
      STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Sixty-seven patients
      with local cartilage defects (mean size, 2.4 cm(2); standard deviation, 1.5
      cm(2)) of the femoral condyle underwent characterized chondrocyte implantation (n
      = 33) or microfracture (n = 34), followed by an identical rehabilitation
      protocol. Activity levels (assessed using the Activity Rating Scale) and
      functional outcome were determined at baseline, and 1 and 2 years after surgery.
      Functional outcome was based on the pooled symmetry index (derived from
      isokinetic knee extension strength and 3 one-legged hop tests). Patients'
      participation in low-load activities during the first 3 months after surgery was
      assessed using rehabilitation data. Mixed linear model analyses and Wilcoxon rank
      sum tests were used. RESULTS: Activity levels in patients treated with
      characterized chondrocyte implantation and microfracture were comparable at 1 and
      2 years after surgery. Preinjury activity levels showed no relationship to
      functional outcome. Lack of postoperative low-load activities resulted in a
      significantly worse functional outcome (mean pooled symmetry index 78.2%)
      compared with high levels of postoperative surgery low-load activities (mean
      pooled symmetry index 92.4%). CONCLUSION: Despite differences between the
      characterized chondrocyte implantation and microfracture procedures, patients'
      activity levels were comparable at 2 years after surgery. Lack of low-load
      activities after surgery adversely affected functional outcome.

PMID- 19861695
TI  - Midterm results of surgical treatment for adult osteochondritis dissecans of the
      knee.
AB  - BACKGROUND: Determination of appropriate treatment options for adult
      osteochondritis dissecans is difficult, as most published papers on surgical
      osteochondritis dissecans treatment report outcomes in a population consisting of
      both adult and juvenile patients. PURPOSE: This study examines the outcomes of
      surgical procedures in patients with adult osteochondritis dissecans. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: The cohort included 46 adult
      patients (48 knees) with adult osteochondritis dissecans of the knee who had
      undergone surgical treatment (debridement, drilling, loose-body removal,
      arthroscopic reduction and internal fixation, microfracture, osteochondral
      allograft, or autologous chondrocyte implantation). The average patient age was
      34 +/- 9.5 years (range, 20-49) and patients were followed for 4.0 +/- 1.8 years.
      The mean defect size was 4.5 +/- 2.7 cm(2). Outcomes were assessed via clinical
      assessment and established outcome scales, including the Lysholm, International
      Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score
      (KOOS), Tegner, Cincinnati, and Short Form-12. RESULTS: Statistically significant
      improvement (P < .05) was noted in all outcome scales, including Noyes, Tegner,
      Lysholm, IKDC, KOOS (subdivided into 5 categories including Pain, Symptoms,
      Activities of Daily Living, Sport, and Quality of Life), Short Form-12 Physical,
      and Short Form-12 Mental. Seven knees (14%) had clinical failure of the initial
      treatment and underwent a revision procedure at a mean follow-up of 14 months.
      Patients treated with arthroscopic reduction and internal fixation and loose-body
      removal demonstrated a statistically higher postoperative percentage score
      increase for the KOOS Sport (P = .008) and KOOS Quality of Life (P = .03)
      categories than those treated with an osteochondral allograft. CONCLUSION:
      Patients with adult osteochondritis dissecans of the knee, treated with surgical
      cartilage procedures, show durable function and symptomatic improvement at a mean
      4.0 years of follow-up. Patients treated with arthroscopic reduction and internal
      fixation and loose-body removal demonstrated a greater improvement in outcome
      scores than those treated with osteochondral allograft.

PMID- 19861696
TI  - Return to sports participation after articular cartilage repair in the knee:
      scientific evidence.
AB  - BACKGROUND: Articular cartilage injury in the athlete's knee presents a difficult
      clinical challenge. Despite the importance of returning injured athletes to
      sports, information is limited on whether full sports participation can be
      successfully achieved after articular cartilage repair in the knee. HYPOTHESIS:
      Systematic analysis of athletic participation after articular cartilage repair
      will demonstrate the efficacy of joint surface restoration in high-demand
      patients and help to optimize outcomes in athletes with articular cartilage
      injury of the knee. STUDY DESIGN: Systematic review. METHODS: A comprehensive
      literature review of original studies was performed to provide information about
      athletic participation after articular cartilage repair. The athlete's ability to
      perform sports postoperatively was assessed by activity outcome scores, rate of
      return to sport, timing of the return, level of postoperative sports
      participation, and the continuation of athletic activity over time. RESULTS:
      Twenty studies describing 1363 patients were included in the review, with an
      average follow-up of 42 months. Return to sports was possible in 73% overall,
      with highest return rates after osteochondral autograft transplantation. Time to
      return to sports varied between 7 and 18 months, depending on the cartilage
      repair technique. Initial return to sports at the preinjury level was possible in
      68% and did not significantly vary between surgical techniques. Continued sports
      participation at the preinjury level was possible in 65%, with the best
      durability after autologous chondrocyte transplantation. Several factors affected
      the ability to return to sport: athlete's age, preoperative duration of symptoms,
      level of play, lesion size, and repair tissue morphology. CONCLUSION: Articular
      cartilage repair in the athletic population allows for a high rate of return to
      sports, often at the preinjury level. Return to sports participation is
      influenced by several independent factors. The findings provide pertinent
      information that is helpful for the clinical decision-making process and for the
      management of the athlete's postoperative expectations.

PMID- 19861693
TI  - The role of mitochondria in the pathophysiology of skeletal muscle insulin
      resistance.
AB  - Multiple organs contribute to the development of peripheral insulin resistance,
      with the major contributors being skeletal muscle, liver, and adipose tissue.
      Because insulin resistance usually precedes the development of type 2 diabetes
      mellitus (T2DM) by many years, understanding the pathophysiology of insulin
      resistance should enable development of therapeutic strategies to prevent disease
      progression. Some subjects with mitochondrial genomic variants/defects and a
      subset of lean individuals with hereditary predisposition to T2DM exhibit
      skeletal muscle mitochondrial dysfunction early in the course of insulin
      resistance. In contrast, in the majority of subjects with T2DM the plurality of
      evidence implicates skeletal muscle mitochondrial dysfunction as a consequence of
      perturbations associated with T2DM, and these mitochondrial deficits then
      contribute to subsequent disease progression. We review the affirmative and
      contrarian data regarding skeletal muscle mitochondrial biology in the
      pathogenesis of insulin resistance and explore potential therapeutic options to
      intrinsically modulate mitochondria as a strategy to combat insulin resistance.
      Furthermore, an overview of restricted molecular manipulations of skeletal muscle
      metabolic and mitochondrial biology offers insight into the mitochondrial role in
      metabolic substrate partitioning and in promoting innate adaptive and maladaptive
      responses that collectively regulate peripheral insulin sensitivity. We conclude
      that skeletal muscle mitochondrial dysfunction is not generally a major initiator
      of the pathophysiology of insulin resistance, although its dysfunction is
      integral to this pathophysiology and it remains an intriguing target to
      reverse/delay the progressive perturbations synonymous with T2DM.

PMID- 19861698
TI  - Midterm to long-term longitudinal outcome of autologous chondrocyte implantation
      in the knee joint: a multilevel analysis.
AB  - BACKGROUND: Autologous chondrocyte implantation is a cell therapeutic approach
      for the treatment of chondral and osteochondral defects in the knee joint. The
      authors previously reported on the histologic and radiologic outcome of
      autologous chondrocyte implantation in the short- to midterm, which yields mixed
      results. PURPOSE: The objective is to report on the clinical outcome of
      autologous chondrocyte implantation for the knee in the midterm to long term.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Eighty patients who
      had undergone autologous chondrocyte implantation of the knee with mid- to long
      term follow-up were analyzed. The mean patient age was 34.6 years (standard
      deviation, 9.1 years), with 63 men and 17 women. Seventy-one patients presented
      with a focal chondral defect, with a median defect area of 4.1 cm(2) and a
      maximum defect area of 20 cm(2). The modified Lysholm score was used as a self
      reporting clinical outcome measure to determine the following: (1) What is the
      typical pattern over time of clinical outcome after autologous chondrocyte
      implantation; and (2) Which patient-related predictors for the clinical outcome
      pattern can be used to improve patient selection for autologous chondrocyte
      implantation? RESULTS: The average follow-up time was 5 years (range, 2.7-9.3).
      Improvement in clinical outcome was found in 65 patients (81%), while 15 patients
      (19%) showed a decline in outcome. The median preoperative Lysholm score of 54
      increased to a median of 78 points. The most rapid improvement in Lysholm score
      was over the 15-month period after operation, after which the Lysholm score
      remained constant for up to 9 years. The authors were unable to identify any
      patient-specific factors (ie, age, gender, defect size, defect location, number
      of previous operations, preoperative Lysholm score) that could predict the change
      in clinical outcome in the first 15 months. CONCLUSION: Autologous chondrocyte
      implantation seems to provide a durable clinical outcome in those patients
      demonstrating success at 15 months after operation. Comparisons between other
      outcome measures of autologous chondrocyte implantation should be focused on the
      clinical status at 15 months after surgery. The patient-reported clinical outcome
      at 15 months is a major predictor of the mid- to long-term success of autologous
      chondrocyte implantation.

PMID- 19861697
TI  - Chondrocyte viability is higher after prolonged storage at 37 degrees C than at 4
      degrees C for osteochondral grafts.
AB  - BACKGROUND: Osteochondral allografts are currently stored at 4 degrees C for 2 to
      6 weeks before implantation. At 4 degrees C, chondrocyte viability, especially in
      the superficial zone, deteriorates starting at 2 weeks. Alternative storage
      conditions could maintain chondrocyte viability beyond 2 weeks, and thereby
      facilitate increased graft availability and enhanced graft quality. PURPOSE: The
      objective of the study was to determine the effects of prolonged 37 degrees C
      storage compared with traditional 4 degrees C storage on chondrocyte viability
      and cartilage matrix content. STUDY DESIGN: Controlled laboratory study. METHODS:
      Osteochondral samples from humeral heads of adult goats were analyzed (i) fresh,
      or after storage in medium for (ii) 14 days at 4 degrees C including 10% fetal
      bovine serum, (iii) 28 days at 4 degrees C including 10% fetal bovine serum, (iv)
      28 days at 37 degrees C without fetal bovine serum, (v) 28 days at 37 degrees C
      including 2% fetal bovine serum, or (vi) 28 days at 37 degrees C including 10%
      fetal bovine serum. Portions of samples were analyzed by microscopy after
      LIVE/DEAD staining to determine chondrocyte viability and density, both en face
      (to visualize the articular surface) and vertically (overall and in superficial,
      middle, and deep zones). The remaining cartilage was analyzed for sulfated
      glycosaminoglycan and collagen. RESULTS: The 37 degrees C storage maintained high
      chondrocyte viability compared with 4 degrees C storage. Viability of samples
      after 28 days at 37 degrees C was approximately 80% at the cartilage surface en
      face, approximately 65% in the superficial zone, and approximately 70% in the
      middle zone, which was much higher than approximately 45%, approximately 20%, and
      approximately 35%, respectively, in 4 degrees C samples after 28 days, and
      slightly decreased from approximately 100%, approximately 85%, and approximately
      95%, respectively, in fresh controls. Cartilage thickness, glycosaminoglycan
      content, and collagen content were maintained for 37 degrees C and 4 degrees C
      samples compared with fresh controls. CONCLUSION: The 37 degrees C storage of
      osteochondral grafts supports long-term chondrocyte viability, especially at the
      vulnerable surface and superficial zone of cartilage. CLINICAL RELEVANCE: Storage
      of allografts at a physiologic temperature of 37 degrees C may prolong storage
      duration, improve graft availability, and improve treatment outcomes.

PMID- 19861699
TI  - Recommendations and treatment outcomes for patellofemoral articular cartilage
      defects with autologous chondrocyte implantation: prospective evaluation at
      average 4-year follow-up.
AB  - BACKGROUND: Reported results of autologous chondrocyte implantation for chondral
      lesions in the patellofemoral joint have been encouraging when combined with
      realignment procedures. PURPOSE: The objective of this study was to examine the
      clinical results of a patient cohort undergoing autologous chondrocyte
      implantation of the patellofemoral joint and elucidate characteristics associated
      with successful implantation. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: The cohort included 62 patients who underwent autologous chondrocyte
      implantation of the PF joint. The mean defect size was 4.2 cm(2) (+/-1.6). The
      average age was 31.8 years (range, 15.8-49.4), and the average follow-up was 4
      years (range, 2-7). Outcomes were assessed via clinical assessment and
      established outcome scales, including the Lysholm, International Knee
      Documentation Committee, Knee Injury and Osteoarthritis Outcome Scale (KOOS;
      includes the 5 categories of Pain, Symptoms, Activities of Daily Living, Sport,
      and Quality of Life), Tegner, Cincinnati, and Short Form-12. RESULTS: Mean
      improvement in the preoperative to postoperative scores was significant for the
      Lysholm (37-63, P <.001), International Knee Documentation Committee (31-57, P
      <.001), KOOS Pain (48-71, P <.001), KOOS Symptoms (51-70, P <.001), KOOS
      Activities of Daily Living (60-80, P <.001), KOOS Sport (25-42, P <.001), KOOS
      Quality of Life (24-49, P <.001), Short Form-12 Physical (38-41, P <.05),
      Cincinnati (43-63, P <.005), and Tegner (4-6, P <.05), but not for the Short Form
      12 Mental. There was no statistical difference between outcomes in patients with
      a history of a previous failed cartilage procedure compared with those patients
      without a prior cartilage procedure (P > .05). Patients undergoing
      anteromedialization tended toward better outcomes than those without realignment.
      Forty-four percent of patients needed a subsequent procedure. There were 4
      clinical failures (7.7%), which were defined as progression to arthroplasty or
      conversion to osteochondral allograft transplantation. CONCLUSION: Autologous
      chondrocyte implantation is a viable treatment option for chondral defects of the
      patellofemoral joint. Combined autologous chondrocyte implantation with
      anteromedialization improves outcomes more than autologous chondrocyte
      implantation alone. Patients with failed prior cartilage procedures can also
      expect sustained and clinically meaningful improvement.

PMID- 19861700
TI  - Matrix-assisted autologous chondrocyte transplantation for the repair of
      cartilage defects of the knee: systematic clinical data review and study quality
      analysis.
AB  - BACKGROUND: The clinical application of the second-generation tissue-engineering
      approach for the treatment of cartilage lesions has been documented for different
      types of scaffolds, but systematic information on clinical efficacy and long-term
      results is not available. PURPOSE: To analyze and assess the quality of clinical
      studies on different products in the emerging field of matrix-assisted autologous
      chondrocyte transplantation. The secondary purpose of this review was to improve
      the quality assessment of studies by modifying the Coleman methodology score
      (CMS). STUDY DESIGN: Systematic review. METHODS: For this review, a literature
      search was performed to identify all published and unpublished clinical studies
      of matrix-assisted (second-generation) autologous chondrocyte transplantation
      using the following medical electronic databases: MEDLINE, MEDLINE preprints,
      EMBASE, CINAHL, Life Science Citations, and British National Library of Health,
      including the Cochrane Central Register of Controlled Trials (CENTRAL). The
      search period was January 1, 1995, to July 1, 2008. To better assess cartilage
      related studies, a modification of the CMS was proposed. RESULTS: Eighteen
      studies were included in the analysis, reporting on 731 patients with an average
      follow-up of 27.3 months (6.5-60.0 months). Of the 18 studies, 2 were randomized
      controlled studies, 3 were prospective comparative studies, 11 were prospective
      cohort studies or prospective case series, and 2 were retrospective case series.
      Original CMSs for these studies (55.1 +/- 1.6) were significantly higher than
      those of cartilage repair studies in general (43.5 +/- 1.6, P < .0001) reported
      in 2005. The statistical analysis indicated that the modified CMS showed higher
      correlations and lower variability of correlations among 3 reviewers. CONCLUSION:
      The quality of the currently available data on second-generation autologous
      chondrocyte transplantation is still limited by study designs. The modified CMS
      has demonstrated better sensitivity and reproducibility with respect to the
      original score, so it can be recommended for cartilage clinical studies
      evaluation.

PMID- 19861701
TI  - Treatment of full-thickness chondral defects with hyalograft C in the knee: a
      prospective clinical case series with 2 to 7 years' follow-up.
AB  - BACKGROUND: Tissue engineering has become available for cartilage repair in
      clinical practice. HYPOTHESIS: The treatment of full-thickness chondral defects
      in the knee with a hyaluronan-based scaffold seeded with autologous chondrocytes
      provides stable improvement of clinical outcome up to 7 years. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Fifty-three patients with deep
      osteochondral defects in the knee were treated with Hyalograft C. The mean age at
      implantation was 32 +/- 12 years, the mean defect size was 4.4 +/- 1.9 cm(2), and
      the mean body mass index was 24.5 +/- 3.8 kg/m(2). Implantations were performed
      with miniarthrotomy or arthroscopy. The primary indications for implantation with
      Hyalograft C included young patients with a stable joint, normal knee alignment,
      and isolated chondral defects with otherwise healthy adjacent cartilage. The
      secondary indications were patients who did not meet the primary indication
      criteria or were salvage procedures. Forty-two patients with primary indications
      and 11 patients with secondary indications were evaluated. Outcome was evaluated
      with the International Cartilage Repair Society and International Knee
      Documentation Committee scales, the Lysholm score, the modified Cincinnati score,
      and with Kaplan-Meier survival analysis. Statistical analysis consisted of
      bivariate correlation analysis and unpaired, 2-tailed t tests. RESULTS: A highly
      significant increase (P <.001) in all knee scores was found in patients treated
      for the primary indications. Nine of 11 secondary indication cases underwent
      total knee arthroplasty due to persisting pain between 2 and 5 years after
      implantation. Graft failure occurred in 3 of 42 patients with primary indication
      between 6 months and 5 years after implantation. Kaplan-Meier survival
      demonstrated significantly different chances for survival between primary and
      secondary outcome and between simple, complex, and salvage cases, respectively (P
      <.001). CONCLUSION: Hyalograft C autograft provides clinical improvement in
      healthy young patients with single cartilage defects. Less complicated surgery
      and lower morbidity are considered advantages of the technique. The results of
      treatment with Hyalograft C as a salvage procedure or in patients with
      osteoarthritis are poor.

PMID- 19861702
TI  - Coalition contract management as a systems change strategy for HIV prevention.
AB  - Racial and Ethnic Approaches to Community Health (REACH) 2010 provided a unique
      opportunity for minority community-based organizations (CBOs) to work together to
      eliminate disparities in HIV disease. A coalition was formed in Broward County to
      respond to the REACH 2010 program announcement, a university was chosen to
      coordinate efforts, and contracts were negotiated with CBO partners to develop,
      implement, and evaluate a community action plan. Contract management provided
      stability, focus, and a mechanism for coalition partners to measure progress
      toward achieving project objectives. By emphasizing documentation as well as the
      delivery of services, however, contract conditions also placed a heavy burden on
      educational outreach workers, restricted the reimbursable activities of member
      organizations, and created friction between minority agencies and university
      staff. Although the coalition met many of its objectives, the introduction and
      enforcement of a mutually agreed on set of rules and obligations as a way of
      promoting systems change in Broward County failed to make a lasting impact among
      community partners. CBOs continued to compete with one another for HIV prevention
      project funding and stopped collaborating as closely with another when federal
      support for our REACH 2010 community demonstration project ran out.

PMID- 19861703
TI  - Relaunching a national social marketing campaign: expectations and challenges for
      the "new" ParticipACTION.
AB  - ParticipACTION is a Canadian physical activity communications and social
      marketing organization that has been relaunched in 2007 after a 6-year hiatus.
      The purpose of this study is to qualitatively identify and describe the
      expectations and challenges the relaunch of the new ParticipACTION may present
      for existing physical activity organizations. Using a purposeful sampling
      strategy, the authors conduct semistructured telephone interviews with 49 key
      informants representing a range of national, provincial, and local organizations
      with a mandate to promote physical activity. Overall, there is strong support in
      seeing ParticipACTION relaunched. However, organizational expectations and/or
      their ideal vision for it are mixed. Organizations envision and support its
      performing an overarching social marketing and advocacy role, and in providing
      tools and resources that supplement existing organizational activities. Four
      major organizational challenges are identified concerning overlapping mandates,
      partnership and leadership concerns, competition for funding, and capacity
      concerns. Social marketing initiatives, such as ParticipACTION, may not be able
      to maximize their impact unless they address the expectations and concerns of
      competing organizations with a mandate to promote physical activity.

PMID- 19861705
TI  - 50 pointers for a new hospice social worker.

PMID- 19861704
TI  - Regulation of gonadotropin-releasing hormone (GnRH) receptor-I expression in the
      pituitary and ovary by a GnRH agonist and antagonist.
AB  - The aim of the current study was to examine the effects of gonadotropin-releasing
      hormone agonist (GnRH-a) and antagonist (GnRH-ant) on the expression of GnRH
      receptor-I (GnRHR-I) in pituitary and ovaries in cyclophosphamide (CTX)
      chemotherapeutic rats and to investigate the possible mechanism of interventions
      of GnRH-a and GnRH-ant in CTX-induced ovarian damage. In total, 36 female rats
      were distributed into 6 groups at random: normal saline (NS) group, CTX group,
      GnRH-a + NS group, GnRH-a + CTX group, GnRH-ant + NS group, and GnRH-ant + CTX
      group. After the rats were killed, the expression of GnRHR-I messenger RNAs
      (mRNAs) and proteins in pituitary and ovaries were examined by reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively.
      The distribution of GnRHR-I in various compartments of the ovaries was observed
      by immunohistochemistry. Significant downregulation of GnRHR-I mRNA and protein
      expression in the pituitary were observed after treatment with GnRH-a or GnRH
      ant. Moreover, GnRH-ant was more potent for this direct and fast inhibition. In
      ovary, GnRHR-I expression was significantly downregulated by GnRH-a. Although
      GnRH-ant slightly decreased the ovarian expression of GnRHR-I mRNA, the protein
      level was only weakly changed. In the ovarian compartment, GnRHR-ant groups had
      markedly GnRHR-I expression in early and late growing follicles compared to GnRHR
      a groups that exhibited decreased expression of GnRHR-I, especially in late
      growing follicles. In summary, this study presents evidence for the different
      regulating effects of GnRH-a and GnRH-ant on the expression of GnRHR-I in
      pituitary and ovaries, which may provide insight into the mechanism of GnRH-a and
      GnRH-ant interventions on chemotoxic ovarian damage.

PMID- 19861706
TI  - Barriers to hospice use and palliative care services use by African American
      adults.
AB  - This study explored the reasons for low levels of hospice participation by
      African Americans. METHODS: Data about attitudes toward dying and death, advanced
      directives, and barriers to using hospice services were collected from 314 adults
      attending 11 diversely populated churches in North Carolina. RESULTS: Almost all
      participants indicated (91%) willingness to use hospice, particularly if the
      hospice team were diverse (77%). Most are without a living will (72%) or health
      care power of attorney (81%); approximately half (54%) have shared final care
      wishes. DISCUSSION: Despite evidence of a willingness to use hospice, African
      Americans were unlikely to complete advanced directives or share final care
      wishes. However, many were more likely to use hospice if the care team were
      diverse suggesting the importance of culture.

PMID- 19861707
TI  - The price of silence.

PMID- 19861708
TI  - Veterinary education: meeting society's needs.

PMID- 19861709
TI  - The anatomy of accreditation.

PMID- 19861710
TI  - Reflections on the future of veterinary medical education.
AB  - Dr. Keith Prasse is a very distinguished leader in veterinary education. He
      started his career achieving his BS and DVM degrees from Iowa State University
      (ISU). He returned to ISU after a brief period in private practice in Illinois.
      His well-recognized career in veterinary pathology began with his MS and PhD
      degrees, followed by a five-year period of teaching at ISU. Dr. Prasse joined the
      faculty of the University of Georgia in 1972, and thus began a long-term
      partnership with Dr. Bob Duncan that is arguably the foundation of veterinary
      clinical pathology. The textbook they authored, Veterinary Laboratory Medicine:
      Clinical Pathology, or "Duncan and Prasse" as it is known, remains the standard
      today, with later participation from Dr. Ed Mahaffey and most recently Dr. Ken
      Latimer. Dr. Prasse has mentored numerous graduate students and received many
      awards over his 23-year career in teaching, including the Norden Distinguished
      Teaching award twice, once at ISU and once at Georgia. His leadership as
      President of the American College of Veterinary Pathologists was greatly
      acknowledged and appreciated. Dr. Prasse's administrative service at the
      University of Georgia spanned 14 years, first as Associate Dean for Public
      Service and Outreach and later as Dean for eight years, during which time he
      served as President of the Association of American Veterinary Medical Colleges
      (AAVMC). The growth of the College of Veterinary Medicine under Dean Prasse's
      visionary leadership was extraordinary. He led through difficult economic and
      political times, yet the college and its community continued to prosper. His
      legacy at the University of Georgia is indelible and perpetual. His outstanding
      leadership of the college was recognized by the Georgia Veterinary Medical
      Association in 2004, when he was given the Georgia Veterinarian of the Year
      award. Since his retirement from Georgia, Dr. Prasse has contributed greatly to
      the profession and to the AAVMC by leading the Foresight project. Dr. Prasse
      honored those attending the 2009 AAVMC Symposium by giving the Recognition
      Lecture. As always, his address was inspirational, and the substance of it is
      included here. -Sheila W. Allen, Dean, University of Georgia College of
      Veterinary Medicine.

PMID- 19861711
TI  - My thoughts on teaching.
AB  - The Pfizer Distinguished Teacher Award, presented annually to a faculty member at
      each college or school of veterinary medicine in the United States, is the most
      prestigious teaching award in veterinary medicine. Originally this award was
      known as the Norden Award, named in honor of Carl J. Norden, founder of Norden
      Laboratories, but since 1963 it has been sponsored by Pfizer Animal Health.
      Awardees are selected by their individual colleges and schools based on the
      following criteria: teaching excellence in lectures, laboratories, and/or
      clinical settings; support of student learning and development outside of
      traditional venues, such as by counseling, advising of specialty clubs, and so on
      (extracurricular activities); and character and leadership. Students, peers, and
      administrators provide input into the various criteria. Each of the 28 colleges
      or schools of veterinary medicine in the United States is invited to submit the
      dossier of their awardee to a national selection committee sponsored by the
      Association of American Veterinary Medical Colleges (AAVMC). It gives me great
      pleasure to note that the committee has awarded the 2008 Pfizer Teaching Award to
      Dr. Bonnie Smith, Associate Professor of Anatomy, Embryology, and Physiology at
      the Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM) at
      Virginia Tech. Dr. Smith began her faculty service at VMRCVM in 1991, and
      previous to that spent four years on the faculty at North Carolina State
      University. Her ability to make a positive impact in the lives of students and
      their learning has become legendary over the years. Likewise, as a member of the
      Curriculum Board (Committee) and serving on various course design teams, Dr.
      Smith has been a steadying force in guiding the curriculum through various
      iterations. Helping students and faculty keep a sense of balance throughout these
      changes has been one of her major contributions. As a testament to her long-term
      teaching excellence, Dr. Bonnie Smith has received at least 22 different awards
      and citations for teaching excellence, two of which came very early in her career
      while she was at North Carolina State University. Most notable among these many
      awards is the fact that she is now a three-time recipient of the Pfizer Teaching
      Award. Dr. Smith has also been nominated by Student AVMA for a Teaching
      Excellence Award in Basic Sciences and has received an Honorable Mention, Teacher
      of the Year Award from the AVMA. Additionally, she has received an Alumni
      Teaching Award and a University Award for Teaching Excellence, and she has been
      elected to the Virginia Tech Academy of Teaching Excellence. Each of these three
      awards recognizes the best educators on Virginia Tech's faculty. Students have
      been very articulate in their praise of Dr. Smith's teaching. The comments
      received include "She has developed a unique teaching style that infuses
      traditional lectures with her unrelenting energy while never sacrificing content
      or complexity" and "She approaches the material from many angles, with clear
      verbalization of concepts, creatively utilizing stories and metaphors for
      clarification." Finally, a very fitting comment that illustrates her impact on
      her students: "Outside the classroom, Dr. Smith also influences many of us by
      serving as a strong female role model. In the face of life's hardships, she
      perseveres with an unshakably positive spirit. She encourages us to excel in all
      we do within the walls of our school and in our own lives." Peers have likewise
      been most complimentary of Dr. Smith's abilities as an educator. Examples from
      her nomination packet include the following: "Dr. Smith is truly a Master Teacher
      of the college. She has consistently demonstrated exemplary qualities of
      teaching, dedication and work ethic. She has received every teaching award the
      College has to offer and is consistently recognized by students, peers and the
      University" and "She epitomizes the qualities we have come to associate with
      teaching excellence. First and foremost is her dedication and commitment to
      student learning. Second, Dr. Smith's rapport with her students is outstanding
      because she invests the time necessary to gain their trust so she knows exactly
      what they are struggling with in her course. Third, she has the uncommon ability
      and desire to reach into students' minds and hearts to tailor instruction to meet
      individual learning styles and needs. Indeed, Dr. Smith is extremely gifted in
      being able to take complex details and concepts, and simplify, organize and
      present them in a very clear, understandable fashion." Other peer comments
      include: "Dr. Smith's animated and enthusiastic style was very effective and well
      received"; "She is commended for her very good use of metaphors, examples and
      humor"; and "We all agree that attending Dr. Smith's lectures was beneficial to
      us as well as to the students! Keep up the fine work." In summary, Dr. Smith is
      to be sincerely congratulated on receiving this prestigious award. It is well
      deserved, based on her long history of teaching excellence and on the positive
      impact she has had in the lives of her students. -J. Blair Meldrum, Professor of
      Toxicology, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland
      Regional College of Veterinary Medicine, Virginia Tech, and Chair, VMRCVM Pfizer
      Teaching Award Selection Committee.

PMID- 19861712
TI  - Pre-clinical pharmacology training in a student-centered veterinary curriculum.
AB  - The appropriate use of therapeutics is important to both human and animal health.
      The field of pharmacology is rapidly progressing such that it is impossible to
      convey to students every possible piece of information they will need to know
      throughout their veterinary careers. Instead, it is more important to train
      students for lifelong and self-directed learning so that they will be able to
      adapt to the ever-changing pharmaceutical landscape. Western University of Health
      Sciences College of Veterinary Medicine teaches pharmacology using a student
      centered and problem-based curriculum designed to teach students not only the
      basics of pharmacology and clinical pharmacology, but also the personal skills
      needed to continue to learn beyond their formal education. The aim of this
      manuscript is to document the pharmacology curriculum during phase I of the
      veterinary curriculum. Review of the graduating class of 2010's exposure to
      pharmacology learning issues reveals broad-based coverage of major functional and
      mechanistic drug classes as well as peripheral topics, including
      pharmacokinetics, legal and ethical issues, and dosing regimen calculations.
      Previous classes have scored well on external examinations leading to a belief
      that this pharmacology curriculum provides adequate training for graduate
      veterinarians.

PMID- 19861713
TI  - Validity, reliability, and defensibility of assessments in veterinary education.
AB  - In this article, we provide an introduction to and overview of issues of
      validity, reliability, and defensibility related to measurement of student
      performance in veterinary medical education. Validity has to do with the extent
      to which the instrument measures whatever it is supposed to measure, reliability
      has to do with the consistency of measurement, and defensibility deals with the
      appropriate standards of the assessment procedure. An explanation of the methods
      that can be used to determine reliability and validity are given and examples of
      how they have been used in recent research findings are provided. Veterinary
      educators should have an understanding of each of these concepts because
      evaluation of veterinary students and performance measures provides evidence of
      utility of assessment tools, informs teaching practices, and can guide curriculum
      development and revision.

PMID- 19861714
TI  - An approach to teaching animal welfare issues at The Ohio State University.
AB  - Despite the growing importance of animal welfare and the critical role of the
      veterinary profession, animal welfare is not formally taught in many veterinary
      curricula. In addition, veterinary students are often not exposed to current
      contentious animal welfare issues, which are subject to much debate and often
      proposed regulation. To address this deficiency in our curriculum at The Ohio
      State University College of Veterinary Medicine, we have developed a course
      titled "Contemporary Issues in Animal Welfare." Our specific objectives for the
      course are: 1) to provide students with the opportunity to objectively evaluate
      and discuss current issues in the welfare of animals as companions, and in the
      industries of agriculture, science, education, conservation, and entertainment;
      2) to increase students' awareness of current important animal welfare issues;
      and 3) to develop students' skills in the critical evaluation of written and
      visual material used in the scientific literature and lay press. We hope that,
      over time, this teaching model will be considered a means to educate veterinary
      students about animal welfare issues in other veterinary curricula.

PMID- 19861715
TI  - Innovations in food-supply veterinary medicine: the michigan state university
      college of veterinary medicine summer food systems fellowship program.
AB  - The purpose of this article is to outline a new educational model at Michigan
      State University's College of Veterinary Medicine. The Summer Food Systems
      Fellowship Program provides opportunities for food industry-oriented students to
      experience summer employment with agriculture industry partners, and gives the
      industry partners exposure to the veterinary profession.

PMID- 19861716
TI  - A descriptive analysis of personality and gender at the Louisiana State
      University School of Veterinary Medicine.
AB  - The goals of this study were to explore the Myers-Briggs Type Indicator profile
      and gender differences of Louisiana State University veterinary students. A 12
      year composite sample (N = 935) revealed that the personality profile was
      different from the published US population norm, but similar to the bimodal ESTJ
      ISTJ profile found in Louisiana medical students. Significant gender differences
      were found among six of the 16 types. A 12-year trend analysis revealed a
      significant shift away from the prototypical ESTJ-ISTJ profile, culminating in a
      discernable heterogeneous profile for both males and females in the last four
      years. Composite scores for the 2004-2007 cohort (N = 331) revealed that the
      predominant types for women were ENFP, ESFJ, ESTJ, ISFJ, and ISTJ. For men, the
      predominant types were ESTJ, ESTP, INTP, and ISTJ. Post hoc tests confirmed
      significant gender differences for ESTP, INTP, ISTP, and ESFJ types. The evidence
      of significant gender differences and confirmation that personality profiles have
      begun to vary widely across the Myers-Briggs Type Indicator spectrum in the last
      four years have implications at the practical and theoretical levels. This could
      have profound effects on pedagogical considerations for faculty involved in
      veterinary medical education.

PMID- 19861717
TI  - Linking theory to practice in an undergraduate veterinary curriculum: students'
      perspectives.
AB  - Facilitated clinical relevance (FCR) at the University of Nottingham School of
      Veterinary Medicine and Science is a small-group educational model that promotes
      student-centered learning. The objectives of this study were: (1) to examine
      students' opinions of FCR as a learning approach compared with other teaching
      methods; and (2) to establish if gender, year of study, or prior exposure to FCR
      were predictors of attitude. Questionnaires were distributed to undergraduate
      veterinary students (N = 185) in the first and second year of study. Students'
      opinions were assessed by noting their degree of agreement with seven statements
      using a seven-point Likert-type scale. A total of 162 students (87.6%) completed
      the survey instrument. The findings indicate that FCR is highly valued among the
      students. The majority of students regarded FCR as directly relevant for clinical
      preparation because it helps them to integrate pre-clinical and clinical
      knowledge and skills in veterinary medicine. However, commonly identified
      challenges were peer dominance, less cooperative facilitators, and coping with
      the ambiguity of knowledge and reasoning. No significant differences were
      detected in attitude between students in the tested variables (p > 0.05).
      However, being in the first year of study, being male, and having prior exposure
      to FCR was found to predict a negative attitude (p < 0.006). To increase
      students' satisfaction, effective strategies must be designed and implemented to
      provide support for struggling individuals.

PMID- 19861718
TI  - Collaborative, case-based learning: how do students actually learn from each
      other?
AB  - The value of collaborative, case-based, and problem-based learning has received
      increased attention in recent years. Several studies have documented veterinary
      staff and students' generally positive feedback on group learning activities, but
      one largely unaddressed question is how students actually learn from each other.
      This study examined how second-year veterinary students learned from each other
      during a collaborative, case-based learning project. Data were students' written
      reflections on their learning in the veterinary course and the specific learning
      experience, and a matched pre- and post-task questionnaire. Consistent with prior
      research describing veterinary students as individualistic learners, only a third
      of students spontaneously mentioned learning from each other as one of their most
      effective strategies. However, when prompted to describe a time when they felt
      that group members were really learning from each other, students reported highly
      valuable collaborative learning processes, which they explicitly linked to
      learning and understanding benefits. Questionnaire data were consistent, showing
      that students became more positive toward several aspects of the activity as well
      as toward group work in general. One unexpected finding was the lack of a
      relationship between students' self-evaluation of their learning and how well
      group members knew each other. These findings provide strong support for the
      educational value of collaborative, case-based learning. In light of other
      research evidence (using observation data) that the amount of time students
      actually engage in high-level collaborative processes may be rather limited, this
      article points to the need for veterinary teachers to better prepare students for
      group learning activities.

PMID- 19861719
TI  - Veterinary student attitudes toward curriculum integration at James Cook
      University.
AB  - The aim of this study was to investigate the attitudes of veterinary science
      students to activities designed to promote curriculum integration. Students (N =
      33) in their second year of a five-year veterinary degree were surveyed in regard
      to their attitudes to activities that aimed to promote integration. Imaging,
      veterinary practice practicals, and a field trip to a cattle property were
      classified as the three most valuable learning activities that were designed to
      promote integration. Veterinary practice practicals, case studies, and palpable
      anatomy were regarded by students as helping them to learn information presented
      in other teaching sessions. They also appeared to enhance student motivation, and
      students indicated that the activities assisted them with their preparation for
      and performance at examinations. Attitudes to whether the learning exercises
      helped improve a range of skills and specific knowledge varied, with 39-88% of
      students agreeing that specific skills and knowledge were enhanced to a large or
      very large extent by the learning activities. The results indicate that learning
      activities designed to promote curriculum integration helped improve motivation,
      reinforced learning, created links between foundational knowledge and its
      application, and assisted with the development of skills that are related to what
      students will do in their future careers.

PMID- 19861720
TI  - Preparedness and disaster response training for veterinary students: literature
      review and description of the North Carolina State University Credentialed
      Veterinary Responder Program.
AB  - The nation's veterinary colleges lack the curricula necessary to meet veterinary
      demands for animal/public health and emergency preparedness. To this end, the
      authors report a literature review summarizing training programs within
      human/veterinary medicine. In addition, the authors describe new competency-based
      Veterinary Credential Responder training at North Carolina State University
      College of Veterinary Medicine (NCSU CVM). From an evaluation of 257 PubMed
      derived articles relating to veterinary/medical disaster training, 14 fulfilled
      all inclusion requirements (nine were veterinary oriented; five came from human
      medical programs). Few offered ideas on the core competencies required to produce
      disaster-planning and response professionals. The lack of published literature in
      this area points to a need for more formal discussion and research on core
      competencies. Non-veterinary articles emphasized learning objectives, commonly
      listing an incident command system, the National Incident Management System,
      teamwork, communications, and critical event management/problem solving. These
      learning objectives were accomplished either through short-course formats or via
      their integration into a larger curriculum. Formal disaster training in
      veterinary medicine mostly occurs within existing public health courses. Much of
      the literature focuses on changing academia to meet current and future needs in
      public/animal health disaster-preparedness and careers. The NCSU CVM program, in
      collaboration with North Carolina Department of Agriculture and Consumer Service,
      Emergency Programs and University of North Carolina at Chapel Hill School of
      Public Health, operates as a stand-alone third-year two-week core-curriculum
      training program that combines lecture, online, experiential, and group exercises
      to meet entry-level federal credentialing requirements. The authors report here
      its content, outcomes, and future development plans.

PMID- 19861721
TI  - The importance of knowledge, skills, and attitude attributes for veterinarians in
      clinical and non-clinical fields of practice: a survey of licensed veterinarians
      in Quebec, Canada.
AB  - To improve content validity and the pertinence of outcome assessment tools used
      for the undergraduate Doctor of Veterinary Medicine program at the University of
      Montreal's Faculte de medecine veterinaire, a survey of members of the Quebec
      veterinary association was conducted. This survey aimed to determine the
      importance of a list of 71 attributes-categorized as knowledge, general skills,
      specific skills, and attitudes-for clinical and non-clinical types of
      professional activities. The results indicated that all basic knowledge
      components, general skills, and attitudes were equally important for all types of
      veterinary professional activities, while the importance of specific skills was
      significantly different for clinical practice and non-clinical fields. It was
      therefore proposed that outcomes assessment surveys of stakeholders, such as
      alumni and employers, be analyzed separately for each type of career option.

PMID- 19861724
TI  - Editorial.

PMID- 19861723
TI  - Special issue on medical bionics.

PMID- 19861722
TI  - Crystal structure of glucagon-like peptide-1 in complex with the extracellular
      domain of the glucagon-like peptide-1 receptor.
AB  - GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells
      in response to food intake. Activation of the GLP-1 receptor potentiates the
      synthesis and release of insulin from pancreatic beta-cells in a glucose
      dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled
      receptors, a subfamily characterized by a large N-terminal extracellular ligand
      binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full
      agonist with similar affinity and potency for the GLP-1 receptor. We recently
      solved the crystal structure of the GLP-1 receptor extracellular domain in
      complex with the competitive antagonist exendin-4(9-39). Interestingly, the
      isolated extracellular domain binds exendin-4 with much higher affinity than the
      endogenous agonist GLP-1. Here, we have solved the crystal structure of the
      extracellular domain in complex with GLP-1 to 2.1 Aresolution. The structure
      shows that important hydrophobic ligand-receptor interactions are conserved in
      agonist- and antagonist-bound forms of the extracellular domain, but certain
      residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is
      a kinked but continuous alpha-helix from Thr(13) to Val(33) when bound to the
      extracellular domain. We supplemented the crystal structure with site-directed
      mutagenesis to link the structural information of the isolated extracellular
      domain with the binding properties of the full-length receptor. The data support
      the existence of differences in the binding modes of GLP-1 and exendin-4 on the
      full-length GLP-1 receptor.

PMID- 19861725
TI  - Health effects of magnetic fields generated from power lines: new clues for an
      old puzzle.
AB  - Thirty years ago, Nancy Wertheimer and Ed Leeper published the first report on
      the association between childhood cancer and "electrical current configuration"
      of houses in Denver, Colorado. In 2001 the International Agency for Research on
      Cancer defined 50-60 Hz magnetic fields as "possibly carcinogenic to humans"
      because of the "limited evidence" of carcinogenicity of residential exposure
      relatively to childhood leukemia. With respect to health effects other than
      cancer, namely neurodegenerative disorders, miscarriage, subtle differences in
      the timing of melatonin release, altered autonomic control of the heart, and
      changes in the number of natural killer cells, some open questions still remain.
      Several authors recommended further investigation of the possible long-term
      effects of magnetic fields, focussing on populations experiencing high exposure
      levels. In this frame a research team of ISS searched for a suitable location to
      implement an epidemiological study aimed at a wide range of outcomes for which a
      priori hypotheses could be formulated. The recently published findings of this
      project showed an increase of primary and secondary malignant neoplasms,
      ischaemic disease and haematological diseases. Future studies should thus address
      the most exposed sectors of the population, take into account different outcomes
      (all neoplasms, neurodegenerative diseases, immunological disorders, specific
      cardiovascular effects) and follow research protocols that enable subsequent
      pooled analyses. A precautionary approach may provide the frame for decision
      making where the available resources for environmental remediation be
      prioritatively allocated to worst-off situations.

PMID- 19861726
TI  - A few remarks on the rules about personal data protection when conducting
      clinical trials in Italy, also from abroad.
AB  - The Italian Authority for the Protection of Personal Data has definitively
      adopted the Guidelines for data processing within the framework of clinical drug
      trials. The Guidelines are addressed to sponsors and other subjects who
      intervene, also from abroad, in clinical trials. The document provides practical
      instructions for the processing of personal data of human subject participating
      in clinical trials.

PMID- 19861727
TI  - Biodosimetric tools for a fast triage of people accidentally exposed to ionising
      radiation.

PMID- 19861728
TI  - Types of radiation mass casualties and their management.
AB  - Management of radiation mass casualty exposure that may occur as a result of
      nuclear or radiation accident will depend on the type of accident, and of the
      knowledge about the actual radiation exposure situation for those who might be
      involved. Management of the public after an accident in a nuclear or radiation
      installation will follow existing specific emergency plans, and will take
      advantage of existing radiation monitoring systems. In other radiation mass
      casualty exposures, whenever accidental or malevolent use of radiation, there
      will be a requirement to employ screening programs for indentifying and sorting
      out exposed people (radiological triage), who will need medical treatment and/or
      other assistance like decontamination and individual dose assessment. In the
      later stage after the accident the monitoring for dose assessment purposes for
      those who will need medical or public health assistance will be required. Demand
      for dose assessment for large groups of individuals may create the need for
      international assistance. Prompt and credible public information is vital in all
      radiation emergencies, and it would be even more important in situations when
      radiation mass casualties result from exposures to nuclear or radiological
      material out of regulatory control. In such situations unpredictability of the
      event creates increase in the risk perception and public communication activities
      of the authorities will be the key element to prevent unnecessary fear and panic,
      and the measure to reassure the populace.

PMID- 19861729
TI  - Cytogenetic damage analysed by the dicentric assay.
AB  - Biological dosimetry, based on the analysis of dicentric chromosomes, is an
      internationally established, independent method applied in the area of radiation
      protection. The biodosimetry is mainly performed, in addition to physical
      dosimetry, with the aim of individual dose assessment, especially after unclear
      or suspected radiation dose exposures. However, a new biodosimetrical challenge
      has emerged in recent years in the form of a possible large scale radiation
      accident potentially involving large numbers of exposed persons. In order to be
      prepared to act in an efficient manner in such an accident, the established
      cytogenetic laboratories have increased their cooperation at the national and
      international level. General experience and results of intercomparisons are
      reported and future options to increase sample throughput are outlined.

PMID- 19861730
TI  - The micronucleus assay in radiation accidents.
AB  - The cytokinesis-block micronucleus assay in peripheral blood lymphocytes is a
      standardised and validated technique for biodosimetry. Automated scoring of
      micronuclei allows large scale applications as in population triage in case of
      radiation accidents or malevolent use of radioactive sources. The dose detection
      limit (95% confidence) of the micronucleus assay for individual dose assessment
      is restricted to 0.2 Gy but can be decreased to 0.1 Gy by scoring centromeres in
      micronuclei using fluorescence in situ hybridization (FISH). In the past the
      micronucleus assay was applied for a number of large scale biomonitoring studies
      of nuclear power plant workers and hospital workers. Baseline micronucleus
      frequencies depend strongly on age and gender. The assay was also already used
      for biodosimetry of radiation accidents. In a multiple endpoint biodosimetry
      study for dose assessment of a worker exposed accidentally in 2003 to X-rays, a
      good agreement was obtained between dose estimates resulting from the
      micronucleus assay, the scoring of dicentrics and translocations. Automated
      scoring of micronuclei in combination with centromere signals, allowing
      systematic biodosimetry of exposed populations, remains a challenge for the
      future.

PMID- 19861731
TI  - gamma-H2AX as protein biomarker for radiation exposure.
AB  - For large scale exposures of the human population to ionising radiation, there is
      a need for cost-effective high throughput assessment of radiation exposure levels
      from biological samples to allow triage decisions to be made. Here we discuss the
      usefulness of the DNA damage marker gamma-H2AX for this purpose. Foci of gamma
      H2AX form in response to radiation-induced DNA doublestrand breaks and can be
      quantified by immunofluorescence microscopy or flow cytometry. Several studies
      have analysed this marker in patients' blood samples to determine radiation
      exposures during various diagnostic or therapeutic radiation treatments. Such
      planned exposures involve only a moderate number of samples which can be obtained
      at a prearranged time following exposure. In contrast, application of this method
      as a triage tool in large scale radiological emergencies demands high throughput
      sample processing and analysis. The rapid kinetics of gamma-H2AX induction and
      loss presents a major challenge to its successful application as a triage tool.
      These and other as yet unresolved questions are discussed.

PMID- 19861732
TI  - Cell response to ionising radiation analysed by gene expression patterns.
AB  - Following ionising radiation exposure of living cells several mechanisms are
      activated through gene modulations. The measurement of these modifications can be
      done with QT-PCR and, since about 10 years, microarray technique. The latter
      approach has the advantage to allow a global monitoring of the complex cellular
      responses to radiation-induced stress and has been proposed to be used for dose
      assessment. Even if some publications have identified sets of genes specific to
      given doses, and that some of the genes have an induction proportional to the
      dose, a precise estimation of the received dose seems difficult with gene
      expression, at least in the near future. Nevertherless, in vivo studies have
      shown that gene profiles of individuals chronically exposed to a cumulative dose
      of more than 10 mSv are significantly modified. This highlights the great
      potential of microarray approaches in the detection of low dose exposure.

PMID- 19861733
TI  - Protein biomarkers for radiation exposure: towards a proteomic approach as a new
      investigation tool.
AB  - Early biomarkers of radiation injury are critical for triage, treatment, and
      follow-up of large numbers of people exposed to ionising radiation after
      terrorist attacks or nuclear accident. Operational monoparametric protein or
      amino acid biomarkers (amylase, Flt3-Ligand, citrulline) can help for the
      diagnostic of radiation exposure or injury. However, these biomarkers are not
      sufficient for a fast and accurate triage, and if individuals are assessed more
      than 48 h after exposure. The comparative proteomic approach represents a
      promising powerful tool for the discovery of new radiation biomarkers. In
      association with multivariate statistics, proteomic enables to measure the level
      of hundreds or thousands of proteins at the same time and identifies sets of
      proteins that can discriminate different groups of individuals.

PMID- 19861734
TI  - Radiation-induced signals analysed by EPR spectrometry applied to fortuitous
      dosimetry.
AB  - Dosimetry based on the detection by electron paramagnetic resonance (EPR)
      spectroscopy of ionizing radiation-induced radicals is an established method for
      the retrospective dosimetry of past exposures and the dosimetry of potentially
      exposed persons in radiological emergencies. The dose is estimated by measuring
      the physical damage induced in materials contained in objects placed on or next
      to the potentially exposed person. The aim of this paper is to survey the current
      literature about methodologies and materials that have been proposed for EPR
      dosimetry, in order to identify those that could be suitable for population
      triage according to criteria such as ubiquity, non invasiveness and easy sample
      collection, presence of a post-irradiation EPR signal, negligible background
      signal, linearity of dose-response relationship, minimum detection limit and post
      irradiation signal stability. The paper will survey the features of sugar,
      plastics, glass, clothing tissues, and solid biological tissues (nails, hair and
      calcified tissues).

PMID- 19861735
TI  - Radiation-induced damage analysed by luminescence methods in retrospective
      dosimetry and emergency response.
AB  - The increasing risk of a mass casualty scenario following a large scale
      radiological accident or attack necessitates the development of appropriate
      dosimetric tools for emergency response. Luminescence dosimetry has been reliably
      applied for dose reconstruction in contaminated settlements for several decades
      and recent research into new materials carried close to the human body opens the
      possibility of estimating individual doses for accident and emergency dosimetry
      using the same technique. This paper reviews the luminescence research into
      materials useful for accident dosimetry and applications in retrospective
      dosimetry. The properties of the materials are critically discussed with regard
      to the requirements for population triage. It is concluded that electronic
      components found within portable electronic devices, such as e.g. mobile phones,
      are at present the most promising material to function as a fortuitous dosimeter
      in an emergency response.

PMID- 19861736
TI  - Biodosimetric tools for a fast triage of people accidentally exposed to ionising
      radiation. Statistical and computational aspects.
AB  - Consideration of statistical methodology is essential for the application of
      cytogenetic and other biodosimetry techniques to triage for mass casualty
      situations. This is because the requirement for speed and accuracy in
      biodosimetric triage necessarily introduces greater uncertainties than would be
      acceptable in day-to-day biodosimetry. Additionally, in a large scale accident
      type situation, it is expected that a large number of laboratories from around
      the world will assist and it is likely that each laboratory will use one or more
      different dosimetry techniques. Thus issues arise regarding combination of
      results and the associated errors. In this article we discuss the statistical and
      computational aspects of radiation biodosimetry for triage in a large scale
      accident-type situation. The current status of statistical analysis techniques is
      reviewed and suggestions are made for improvements to these methods which will
      allow first responders to estimate doses quickly and reliably for suspected
      exposed persons.

PMID- 19861738
TI  - Ethical problems with neonatal screening.
AB  - The availability of novel technologies, such as tandem-mass-spectrometry (MS/MS)
      and DNA analysis, has expanded tremendously the number of genetic conditions that
      can be diagnosed through neonatal screening programs at birth, including
      conditions that cannot be treated nor prevented, or that will become manifest
      only later in life, or that identify individuals that are only at an increased
      risk of multifactorial conditions. This has increased the number and complexity
      of ethical problems related to newborn screening programs, creating considerable
      confusion and generating controversies and ethical concerns. The experience so
      far gained indicates that, besides the incomplete knowledge of many aspects of
      the conditions to be identified, the majority of screening programs do not pay
      sufficient attention to the problems of communication, information and
      counselling of the parents. Therefore, communication must be substantially
      improved if we wish to increase the efficiency of such programs and avoid
      possible unwanted side effects. Furthermore, ethical issues should receive more
      attention and consideration for a better and more complete understanding of the
      overall impact of neonatal screening programs. This more extensive and ethically
      correct approach should allow us to find an optimal equilibrium between the
      potential benefits and the possible damages deriving from neonatal screening
      programs.

PMID- 19861737
TI  - Survival for cancer patients in Europe.
AB  - Comparing cancer survival among the European countries is important to evaluate
      the performance of Health Care Systems and reduce disparities in access to
      diagnostic and treatment facilities. The EUROCARE project compares survival in
      Europe since the nineties. The EUROCARE- 4 analysed 2 690 922 adult cancer cases
      from 83 cancer registries in 22 European countries, diagnosed in 1995-1999, and
      followed to December 2003. For each cancer site, the European area weighted mean
      and age-standardised country-specific observed and relative survival by age and
      sex is computed. Within-country variation in survival is analysed for selected
      cancers. Survival for most solid cancers, whose prognosis depends largely on
      stage at diagnosis (breast, colorectal, stomach cancers, and skin melanoma), was
      highest in Finland, Sweden, Norway, and Iceland, lower in the UK and Denmark, and
      lowest in the Czech Republic, Poland and Slovenia. France, Switzerland and Italy
      generally had good survival, slightly below that of the Northern countries. For
      all cancers, five-year survival was very variable also for the different sites
      mix. Continuing to monitoring cancer survival in Europe is important to reduce
      differences in access to diagnostic and therapeutic facilities. After publication
      of EUROCARE results, UK and Denmark developed a National cancer plan to improve
      time of diagnosis and treatment.

PMID- 19861739
TI  - Relating with migrants: ethnopsychiatry and psychotherapy.
AB  - After an historical review of cultural anthropology, transcultural psychiatry and
      ethno psychiatry, we will examine the literature on intervention with migrants
      within mental health system. In the first part, we will consider the therapeutic
      relationship with Arab-Muslim patients and look at specific issues such as gender
      differences, individualism, sociality, stigma, religion. The second part will be
      focused on cultural mediation, migration and family intervention and post
      traumatic stress disorder and, finally, the experience of being a foreign
      therapist. Conclusions will discuss the importance of culture, individuality and
      universality of human suffering, when treating a foreign patient.

PMID- 19861740
TI  - Author's misconduct inviting risk: duplicate publication.

PMID- 19861741
TI  - Serum cortisol and testosterone levels in idiopathic central serous
      chorioretinopathy.
AB  - CONTEXT: The preferential occurrence of idiopathic central serous
      chorioretinopathy (ICSC) in males with a typical Type A personality and behavior
      and a relative absence in females is a possible indicator towards the role of
      serum cortisol and /or the male sex hormone testosterone. AIMS: To study levels
      of cortisol and testosterone in ICSC. SETTINGS AND DESIGN: Case-control study in
      a tertiary care teaching hospital. MATERIALS AND METHODS: The study was conducted
      on 23 cases of ICSC. Twelve patients with unilateral sudden painless loss of
      vision of less than one month duration served as controls. Serum cortisol and
      testosterone levels at 8.00 a.m. were estimated by radioimmunoassay in both
      groups. STATISTICAL ANALYSIS USED: Statistical analysis was done using SPSS 13.0
      software. Independent Sample t-test was applied to analyze statistical
      significance between the two groups. RESULTS: Mean age of patients with ICSC was
      37.1 +/- 9.7 years and 96% of the patients were males. Mean serum cortisol levels
      were significantly higher (P=0.002) in patients with ICSC i.e., 495.02 +/- 169.47
      nano moles/liter (nmol/L) as compared to controls i.e., 362.25 +/- 51.54 nmol/L.
      Mean serum testosterone levels were 3.85 +/- 1.81 nano grams/ml (ngm/ml) and 4.23
      +/- 1.89 ngm/ml in cases and controls respectively and the difference was not
      statistically significant (P=0.58). CONCLUSIONS: ICSC is associated with elevated
      8.00 a.m. serum cortisol levels. However, mean serum testosterone levels in both
      patients of ICSC and controls were within normal range.

PMID- 19861742
TI  - Are current guidelines for categorization of visual impairment in India
      appropriate?
AB  - CONTEXT: Visual disability in India is categorized based on severity. Sometimes
      the disabled person does not fit unambiguously into any of the categories. AIMS:
      To identify and quantify disability that does not fit in the current
      classification, and propose a new classification that includes all levels of
      vision. SETTINGS AND DESIGN: Retrospective chart review of visual disability
      awarded in a teaching hospital. MATERIALS AND METHODS: The last hundred records
      of patients who had been classified as visually disabled were screened for vision
      in both eyes and percentage disability awarded. Data were handled in accordance
      with the Helsinki Declaration. RESULTS: Twenty-one patients had been classified
      as having 30% disability, seven each had 40% and 75%, and 65 had 100% disability.
      Eleven of them did not fall into any of the current categories, forcing the
      disability board to use its own judgment. There was a tendency to over-grade the
      disability (seven of 11; 63.6%). The classification proposed by us is based on
      the national program for control of blindness' definition of normal vision (20/20
      to 20/60), low vision ( < 20/60 to 20/200), economic blindness ( < 20/200 to
      20/400) and social blindness ( < 20/400). It ranges from the mildest disability
      (normal vision in one eye, low vision in the other) up to the most severe grade
      (social blindness in both eyes). CONCLUSIONS: The current classification of
      visual disabilities does not include all combinations of vision; some disabled
      patients cannot be categorized. The classification proposed by us is
      comprehensive, progresses logically, and follows the definitions of the national
      program.

PMID- 19861743
TI  - Utility of QuantiFERON TB gold test in a south Indian patient population of
      ocular inflammation.
AB  - AIM: To study the utility of interferon-g release assays (QuantiFERON TB gold
      test) in a south Indian patient population of intraocular inflammation. DESIGN:
      Evaluation of a diagnostic test- a pilot study from January 2007 to October 2008.
      MATERIALS AND METHODS: QuantiFERON TB gold test was performed on the following
      groups of patients following an informed consent. Group A included healthy
      volunteers without any exposure to tuberculosis (TB) or past history of TB
      (n=22). Group B included patients with active systemic TB diagnosed by the
      demonstration of acid-fast bacilli or by the histopathology finding of caseation
      with granuloma formation from the sputum, lymph node, skin or intestinal biopsies
      (n=26). Group C included patients with uveitis of known etiologies other than
      intraocular TB without any history of exposure to active TB (n=21). Group D
      included patients with a diagnosis of presumed intraocular TB, who responded to
      antitubercular therapy by decreased or no recurrences following treatment and
      with a minimum of nine months follow-up following initiation of antitubercular
      therapy (n=39). RESULTS: The sensitivity and specificity of the QuantiFERON TB
      gold test to pick up active systemic TB was 58% and 77% respectively. The
      sensitivity and specificity of the QuantiFERON TB gold test to pickup intraocular
      TB was 82% and 76% respectively. CONCLUSIONS: QuantiFERON TB gold test alone may
      not be specific for intraocular TB. The significance of this test in a case
      scenario needs to be interpreted with clinical presentation and other evidences
      for intraocular TB.

PMID- 19861744
TI  - Results of intraocular lens implantation with capsular tension ring in subluxated
      crystalline or cataractous lenses in children.
AB  - PURPOSE: To evaluate the outcome of intraocular lens (IOL) implantation using
      capsular tension ring (CTR) in subluxated crystalline or cataractous lenses in
      children. SETTING: Tertiary care setting. MATERIALS AND METHODS: We prospectively
      studied 18 eyes of 15 children with subluxation of crystalline or cataractous
      lenses between 90 degrees up to 210 degrees after phacoemulsification, CTR and
      IOL implantation. Each child was examined for IOL centration, zonular dehiscence
      and posterior capsular opacification (PCO). RESULTS: Age of the patient ranged
      between five to 15 years. Out of 18 eyes, seven had traumatic and 11 had
      spontaneous subluxation of crystalline or cataractous lens. Phacoemulsification
      was successfully performed with CTR implantation in the capsular bag.
      Intraoperative zonular dialysis occurred in two eyes. Anterior vitrectomy was
      performed in six eyes to manage vitreous prolapse. IOL implanted was polymethyl
      methacrylate (PMMA) in eight eyes, hydrophobic acrylic in seven and hydrophilic
      acrylic in three. Follow-up ranged from 24 months to 72 months. Sixteen eyes had
      a best corrected visual acuity of 20/40 or better. Nine eyes developed
      significant PCO and were managed with Neodymium Yttrium Aluminum Garnet (Nd:YAG)
      laser posterior capsulotomy. One eye with acrylic IOL in the capsular bag had IOL
      dislocation after two years which was managed with vitrectomy and secondary trans
      scleral fixation of IOL. CONCLUSIONS: Phacoaspiration with CTR implantation makes
      capsular bag IOL fixation possible in most of the eyes with subluxated
      crystalline or cataractous lenses. PCO still remains a challenge in children with
      successful phacoaspiration with CTR implantation.

PMID- 19861745
TI  - Evaluation of 'vision screening' program for three to six-year-old children in
      the Republic of Iran.
AB  - BACKGROUND: Since 1996, vision screening of three to six-year-old children is
      conducted every year in Iran. We present outcomes of project review held in
      August 2006. MATERIALS AND METHODS: Kindergarten teachers examined vision by
      using Snellen's illiterate 'E' chart. They used torchlight to detect strabismus.
      On a repeat test, if either eye had vision < 20/30, the child was referred to the
      optometrist. A pediatric ophthalmologist examined and managed children with
      strabismus or amblyopia. Provincial managers supervised the screening program.
      The evaluator team assessed the coverage, yield, quality and feasibility, and
      cost-effectiveness of vision screening, as well as magnitude of amblyopia, and
      its risk factors. RESULT: In 2005, 1.4 million (67%) children were examined in
      all provinces of Iran. Opticians examined 90,319 (61%) children with defective
      vision that were referred to them. The prevalence of uncorrected refractive
      error, strabismus and amblyopia was 3.82% (95% CI 3.79 - 3.85), 0.39% (95% CI
      0.38 - 0.40) and 1.25% (95% CI 1.24 - 1.26) respectively. Validity test of 7,768
      children had a sensitivity of 74.5% (95% CI 72.7 - 76.3) and specificity of 97.2%
      (95% CI 96.7 - 97.7). The cost of amblyopia screening was US $ 1.5 per child.
      While the cost of screening and treating one child with amblyopia was US $ 245.
      CONCLUSION: A review of the vision screening of children in Iran showed it with
      screening and useful exercise and had a yield of 1:21. The coverage of vision
      screening was low and the management of children with amblyopia, low vision and
      refractive error needed strengthening.

PMID- 19861747
TI  - Visual impairment in the hearing impaired students.
AB  - BACKGROUND: Ocular problems are more common in children with hearing problems
      than in normal children. Neglected visual impairment could aggravate educational
      and social disability. AIM: To detect and treat visual impairment, if any, in
      hearing-impaired children. SETTING AND DESIGN: Observational, clinical case
      series of hearing-impaired children in schools providing special education.
      MATERIALS AND METHODS: Hearing-impaired children in selected schools underwent
      detailed visual acuity testing, refraction, external ocular examination and
      fundoscopy. Ocular motility testing was also performed. Teachers were sensitized
      and trained to help in the assessment of visual acuity using Snellen's E charts.
      Refractive errors and squint were treated as per standard practice. STATISTICAL
      ANALYSIS: Excel software was used for data entry and SSPS for analysis. RESULTS:
      The study involved 901 hearing-impaired students between four and 21 years of
      age, from 14 special education schools. A quarter of them (216/901, 24%) had
      ocular problems. Refractive errors were the most common morbidity 167(18.5%), but
      only 10 children were using appropriate spectacle correction at presentation.
      Fifty children had visual acuity less than 20/80 at presentation; after providing
      refractive correction, this number reduced to three children, all of whom were
      provided low-vision aids. Other common conditions included strabismus in 12
      (1.3%) children, and retinal pigmentary dystrophy in five (0.6%) children.
      CONCLUSION: Ocular problems are common in hearing-impaired children. Screening
      for ocular problems should be made mandatory in hearing-impaired children, as
      they use their visual sense to compensate for the poor auditory sense.

PMID- 19861746
TI  - Gender inequality in vision loss and eye diseases: evidence from the Sultanate of
      Oman.
AB  - PURPOSE: The data from surveys of vision loss and monitoring of services were
      used to assess changes in gender inequality in Oman. STUDY DESIGN: Retrospective
      review of data collection instruments. MATERIALS AND METHOD: The data sets of 12
      years between 1996 and 2007 were abstracted to assess the gender equality for
      vision loss, eye disease prevalence, and service use. They included two surveys
      (1996 and 2005), Health Information from eye units (1998 and 2007), and eye
      screening in schools. RESULTS: In 1996, the prevalence of bilateral blindness in
      > or = 40 years of age was higher in females [Odd's Ratio (OR) = 0.36 (95%
      Confidence Interval (CI) 0.24 - 0.53)]. Gender differences in the prevalence of
      cataract [OR = 0.82 (95% CI 0.63 - 1.03)] were not significant while trachomatous
      trichaisis (TT) was less in males [OR = 0.33 (95% CI 0.22-0.48)]. In 2005, gender
      differences in the prevalence of bilateral blindness [OR = 0.97 (95% CI 0.71 -
      1.34)] and TT [OR = 0.66 (95% CI 0.42- 1.04)] were not statistically
      significant.But males were associated with higher prevalence of cataract [OR =
      1.26 (95% CI 1.00 - 1.59)]. Surgery rates for cataract, glaucoma and TT were not
      different by gender. More male compared to female patients with diabetic
      retinopathy were treated. Myopia was significantly higher in girls. Compliance of
      spectacle wear was higher in girls. CONCLUSIONS: Gender inequality for eye care
      seems to have reduced in the last 10 years in Oman. However, apart from TT and
      glaucoma patients the difference in service utilization by gender was not
      statistically significant.

PMID- 19861748
TI  - Effectiveness of using teachers to screen eyes of school-going children in Satna
      district of Madhya Pradesh, India.
AB  - AIM: To assess the effectiveness of teachers in a vision screening program for
      children in classes 5th to 12th attending school in two blocks of a district of
      north central India. MATERIALS AND METHODS: Ophthalmic assistants trained school
      teachers to measure visual acuity and to identify obvious ocular abnormalities in
      children. Children with visual acuity worse than 20/30 in any eye and/or any
      obvious ocular abnormality were referred to an ophthalmic assistant. Ophthalmic
      assistants also repeated eye examinations on a random sample of children
      identified as normal (approximately 1%, n=543) by the teachers. Ophthalmic
      assistants prescribed spectacles to children needing refractive correction and
      referred children needing further examination to a pediatric ophthalmologist at
      the base hospital. RESULTS: Five hundred and thirty teachers from 530 schools
      enrolled 77,778 children in the project and screened 68,833 (88.50%) of enrolled
      children. Teachers referred 3,822 children (4.91%) with eye defects for further
      examination by the ophthalmic assistant who confirmed eye defects in 1242
      children (1.80% of all screened children). Myopia (n=410, 33.01%), Vitamin A
      deficiency (n=143, 11.51%) and strabismus (n=134, 10.79%) were the most common
      eye problems identified by the ophthalmic assistant. Ophthalmic assistants
      identified 57.97% referrals as false positives and 6.08% children as false
      negatives from the random sample of normal children. Spectacles were prescribed
      to 39.47% of children confirmed with eye defects. CONCLUSIONS: Primary vision
      screening by teachers has effectively reduced the workload of ophthalmic
      assistants. High false positive and false negative rates need to be studied
      further.

PMID- 19861749
TI  - Combination 20 and 23-gauge transconjunctival vitrectomy: a new approach.
AB  - The advent of smaller gauge instrumentation allows for minimally invasive
      vitreoretinal surgery (MIVS) as compared to conventional pars plana vitrectomy.
      Sutureless posterior segment surgery has the advantages of faster wound healing,
      minimal surgical trauma, decreased convalescence period besides reduced
      postoperative astigmatism; however, slower gel removal and limited peripheral
      vitreous dissection are disadvantages with smaller gauge systems. We herein
      describe a new technique combining 23-gauge and 20-gauge vitrectomy to improve
      the effectiveness and outcomes of vitreoretinal surgery.

PMID- 19861750
TI  - Amyloidosis of lacrimal gland.
AB  - Primary localized amyloidosis of lacrimal gland is a rare occurrence. This report
      describes a female patient with isolated amyloidosis of the lacrimal gland. A 45
      year-old Indian woman presented with a swelling over the left lacrimal gland
      region. Computed tomography showed uniform enlargement of the lacrimal gland. A
      lacrimal gland biopsy revealed amyloidosis. No systemic involvement was detected
      on further investigation. To our knowledge, this is the first report of lacrimal
      gland amyloidosis from India and our report also highlights the importance of
      lacrimal gland biopsy in diagnosing lacrimal gland masses.

PMID- 19861751
TI  - Botulinum toxin in the management of acquired motor fusion deficiency.
AB  - Acquired disruption of motor fusion is a rare condition characterized by
      intractable diplopia. Management of these patients is extremely difficult. Prisms
      in any combination or even surgery may not help relieve their symptoms. We
      describe a longstanding case of acquired motor fusion disruption which was
      managed successfully with botulinum toxin injection.

PMID- 19861752
TI  - A rare cause of nasolacrimal duct obstruction: dentigerous cyst in the maxillary
      sinus.
AB  - The most common abnormality of the lacrimal drainage system is congenital or
      acquired nasolacrimal duct obstruction. The causes of acquired nasolacrimal duct
      obstruction may be primary or secondary. The secondary acquired obstructions may
      result from infection, inflammation, neoplasm, trauma or mechanical causes. The
      maxillary sinus cysts usually obstruct the nasolacrimal duct mechanically.
      Dentigerous cysts are one of the main types of maxillary cysts. These cysts are
      benign odontogenic cysts which are associated with the crowns of unerupted teeth.
      The clinical documentations of mechanical nasolacrimal duct obstructions due to a
      dentigerous cyst in the maxillary sinus are very rare in literature. In this case
      report, we describe a dentigerous cyst with a supernumerary tooth in the
      maxillary sinus in an 11-year-old male child causing an obstruction to the
      nasolacrimal duct. The case was successfully managed surgically by Caldwell Luc
      approach.

PMID- 19861753
TI  - Pattern of use of contact lens among college students: a cross-sectional study in
      coastal Karnataka.
AB  - The use of contact lens (CL) for the correction of refractive errors, cosmetic
      use and their usage as a therapeutic modality for corneal pathologies has
      increased tremendously over the years. The present study was conducted with the
      aim to find a pattern of CL use amongst college students with a focus on the
      rationale for CL use and problems related to their use. This study includes 371
      college students who were current users of CL at the time of the study. Results
      showed that 96.8% of the CL users use the 'daily wear type' of CL. Most quoted
      reasons of usage were comfort and convenience (61.2%) with cosmetic benefit
      (42.9%) as the next most common reply. Common complaints were that of general
      discomfort (foreign body sensation), dry eyes and watering eyes. Educated use of
      CLs amongst its users is advised in view of the symptoms and associated
      complications that may occur.

PMID- 19861754
TI  - Bilateral macular hole secondary to remote lightning strike.
AB  - We report a case of a 16-year-old girl, who was struck by lightning, and
      experienced blurred vision in the right eye (RE) immediately following the
      episode. She reported for ophthalmic evaluation two months later. Examination
      revealed relative afferent pupillary defect in the RE. Posterior subcapsular
      cataract was noted in both eyes. Fundus examination revealed macular holes and
      multiple areas of RPE hyperpigmentation in the periphery in both eyes. Fundus
      fluorescein angiography showed increased choroidal transmission with early
      fluorescence and late fading in the foveal region and retinal pigment epithelium
      (RPE) stippling in the periphery in both eyes. This is the first case report of
      such nature in India to the best of our knowledge.

PMID- 19861755
TI  - Insect wing tarsal foreign body causing conjunctival granuloma and marginal
      keratitis.
AB  - A 37 year old male was referred to our centre for management of episcleritis with
      peripheral keratitis in the right eye. He had a history of ocular discomfort in
      the right eye of 1 week duration. Slitlamp examination revealed marginal
      keratitis between 12'o clock to 2'o clock positions in the right eye. Lid
      eversion revealed an insect wing on the tarsal conjunctiva along with an adjacent
      conjunctival granuloma. The area of the marginal keratitis corresponded to the
      area of the foreign body and the conjunctival granuloma. The probable mechanism
      of the development of marginal keratitis and the conjunctiva granuloma is
      speculated in this case report.

PMID- 19861756
TI  - Congenital orbital teratoma presenting as microphthalmos with cyst.
AB  - We report a rare case of non-communicating large orbital cyst with microphthalmos
      which was surgically separated from the globe and excised. Histopathology
      reported it to be a teratoma. Congenital cystic teratoma should be a part of the
      differential diagnosis in an infant presenting with a clinical picture of
      microphthalmos with orbital cyst, in view of the different management required.

PMID- 19861758
TI  - Minimally invasive Knapp's procedure: modified fornix incision approach.

PMID- 19861757
TI  - Misinnervation in third nerve palsy: vertical synergistic divergence.

PMID- 19861759
TI  - Life after liver transplantation.

PMID- 19861760
TI  - Physiology of the sphincter of Oddi: the present and the future?--Part 2.

PMID- 19861761
TI  - Laparscopic cholecytectoy: a local experience in Sudan.
AB  - OBJECTIVE: Poverty, pressing priorities and tropical diseases prevailed added to
      the factors that delay the implementation of Laparoscopic Cholecystectomy (LC).
      The objective of this study was to assess the feasibility and safety of LC in
      this country (Sudan). SUBJECTS AND METHODS: From June 1995-May 1999, we enrolled
      288 patients presented with symptomatic gallstone disease without pre-selection
      criteria. 242 were females and 46 were males, mean age 48.1 years. RESULTS: LC
      was successful in 201 (94.81%) patients including 49 patients with acute
      cholecystitis. The operation was done the same day of admission and 60 (29.35%)
      were able to leave as a day case. There was no mortality and no common bile duct
      injury. CONCLUSION: LC is feasible, safe and cost effective in Sudan.

PMID- 19861762
TI  - Comparision between per-oral and ultrathin transnasal endoscopy in unsedated
      patients.
AB  - BACKGROUND: This is a prospective study to evaluate the tolerance and
      acceptability of patients for diagnostic ultrathin transnasal
      esophagogastroduodenoscopy compared with the standard peroral route. PATIENTS AND
      METHODS: Both types of endoscopic procedures were explained to the patients.
      Sixty patients were included in this study and subsequently, 30 unsedated
      patients in each group underwent upper gastrointestinal endoscopy. An evaluation
      and questionnaire form both the endoscopist and the patient was recorded. Out of
      the 30 patients who had transnasal endoscopy, 15 had previous peroral endoscopy.
      Oximetry was recorded during the procedure. RESULTS: All patients in both groups
      tolerated the procedure well and it was successfully completed. In the transnasal
      group, three patients had mild epistaxis. Desaturation in the transnasal group
      was the same as compared to the peroral group. From the 30 patients of transnasal
      group, 21 were willing to repeat the procedure if required and eight patients
      were willing to repeat the procedure reluctantly. Only one patient expressed
      preference for the peroral route. The endoscopist's observation revealed that
      scope insertion in both groups was equally tolerated but lens washing and suction
      was not optimal in the transnasal approach. CONCLUSION: Both groups showed good
      tolerability, but the tranasal approach was found to be more acceptable to the
      patient. In the tranasal group, the patients found the procedure less distressing
      and were subsequently more willing for a repeat procedure. Therefore we believe
      that the tranasnal approach to esophagogastroduodenoscopy in diagnostic and
      follow up procedures will rapidly acquire increasing popularity.

PMID- 19861763
TI  - Acute pancreatitis in Saudi patients.
AB  - BACKGROUND: The epidemiology of acute pancreatitis in Saudi Arabia is greatly
      different from that in Western Countries. AIM: To evaluate and compare the risk
      factors and clinical features of acute pancreatitis. PATIENTS AND METHODS: The
      course of acute pancreatitis was retrospectively analyzed in 218 patients who had
      their first attack and were admitted at Riyadh Armed Forces Hospital during the
      period 1.01.85-31.05.97. RESULTS: From these 218, 130 patients were in the age
      group of 20-55 yrs. (74+, 56>), 76 were > 55 yrs. Of age (42 +, 34>) and only 12
      were < 20 yrs. (6 Females, 6 Males). The precipitating cause was biliary disease
      in 147, post-operative in ten, hyperlipidemia in seven, post-ERCP in five,
      infection in four and alcohol in four. Four had rare causes and 37 no obvious
      cause. Severe pancreatitis diagnosed in 70 patients, 51 of them were > 55 yrs. of
      age and 45 were precipitated by biliary disease. Twenty six developed
      complications (21 were > 55 yrs. old) and four deaths. Twenty two patients of
      these who had severe form had diabetes mellitus, 37 had fever at presentation and
      56 had leukocytosis. CONCLUSIONS: The commonest etiology of acute pancreatitis
      was biliary in 147 patients (67.5%) followed by postoperative pancreatitis in 10
      patients (4.6%). Alcohol as etiological factor was rare (1.8%). The epidemiology
      and the risk factors differed markedly in Saudi Arabia, where alcohol is
      prohibited.

PMID- 19861764
TI  - Endoscopic management of a large sigmoid lipoma with intussusception in a young
      woman: case report.

PMID- 19861765
TI  - Abdominal actinomycosis: case reports.

PMID- 19861766
TI  - Esophageal carcinoma presenting as seronegative symmetrical synovitis with
      pitting edema.

PMID- 19861767
TI  - Ribavirin.

PMID- 19861768
TI  - Enterocutaneous fistula.
AB  - Based on the modality of treatment, historically the management of
      enterocutaneous fistula has been grouped into three periods. The era of
      antibiotics (1945-1960), the era of intensive nurse care (1960-1970) and the era
      of intravenous hyperalimentation (1970-1975). Schein's modification of Sitges
      Serra classification of enterocutaneous fistula is now preferred to the old
      classification of high-output type and low output type. A major cause of
      enterocutaneous fistula is technical failure. Serum level of short-turn over
      proteins such as albumin retinal-binding protein, thyroxin binding pre-albumin as
      serum transferring are predictors of mortality and spontaneous fistula closure.
      Immediate surgical correction of the fistula is not a priority of treatment. The
      control of sepsis and adequate nutrition are the two most important aspects of
      management. The use of somatostatin and octreotide has been shown to shorten the
      period of spontaneous closure of the fistula.

PMID- 19861769
TI  - Ulcerative colitis in Saudi Arabia: a retrospective analysis of 33 cases treated
      in a regional referral hospital in Gizan.
AB  - BACKGROUND: Until recently ulcerative colitis (UC) was considered rare among
      Arabs. Information on its occurrence among Saudi is scant and limited to a few
      reports from urban populations. AIM OF STUDY: to assess the frequency and clinico
      pathologic pattern of this disease in a rural population in Gizan region, Saudi
      Arabia. METHODS: thirty three patients found to have UC over a 4-year period in
      King Fahad Central Hospital were analyzed retrospectively. RESULTS: there were 24
      males and nine females patients with UC (ages ranged from 17-70 years, mean age
      43.5 years). The commonest presenting symptoms were abdominal pain and diarrhea
      in 30 and 26 patients respectively. Extra-intestinal manifestations were rare,
      occurred in only two patients. Total or pancolitis was found in ten (30%)
      patients and it was severe in nine of them. The disease extended to the splenic
      flexure in eight (24.2%) of the patients. A total colectomy was required in one
      patient with severe pan-colitis and a focus of malignancy was present in the
      resected specimen. No patient died during the follow-up period that ranged from
      one to six years. CONCLUSION: the study confirmed the occurrence of UC among the
      rural population studied. The male preponderance, the older age at presentation
      and relatively milder diseases appeared to be differentiating features from the
      pattern among western populations.

PMID- 19861770
TI  - Use of percutaneous endoscopic gastrostomy in acute dysphagic stroke.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a widely used method for
      insertion of gastrostomy tube for patients with dysphagia due neuromuscular
      disorders. Aim : this article highlights the role of PEG for such patients, how
      safe, effective than standard gastrostomy in providing long -term nutritional
      support for patients with dysphagic stroke. METHODS: Over a four-year period
      (1995-1998), 27 patients had percutaneous endoscopic gastrostomy performed for
      neuromuscular dysphagia. A Wilson Cook (24G) gastrostomy tube was used and it was
      inserted with Ponsky-Gauderer pull technique. RESULTS: All the patients tolerated
      the procedure well. Stroke (81%) was the most common indication for PEG. Major
      gastroscopic finding was found in eight patients (29%). Minor complication was
      seen in only three patients (11%). CONCLUSION: PEG Feeding is safe, simple and
      effective procedure with no serious side effects. Patients and their relatives
      accept PEG better than nasogastric tube feeding. However, the ideal timing at
      which to institute gastrostomy feeding after dysphagic stroke is still not clear.

PMID- 19861771
TI  - Primary ascitic fluid infection in patients with chronic liver diseases.
AB  - THE AIM OF THE STUDY: to evaluate primary ascitic fluid infection (PAFI) among
      patients with chronic liver disease (CLD), to study the incidence, clinical
      features, laboratory findings and short term prognosis of PAFI and also to
      evaluate factors that may affect incidence and prognosis. PATIENTS AND METHODS:
      Seventy eight patients with CLD were studied between July 1996- to July 1997 in
      Baghdad Teaching Hospital. RESULTS: thirteen patients developed PAFI (16.7%), no
      significant differences in the age or gender between the infected and the non
      infected groups were found. (P > 0.05). The incidence of PAFI is significantly
      higher among patients with Child's Pugh class C (P < 0.005). Low ascitic fluid
      protein ( < 10 g/L) was more common among the infected group, yet this does not
      reach statistical significance (P > 0.05). The presenting symptoms were abdominal
      pain (53.8%), fever (46.2%); abdominal tenderness (38.5%), encephalopathy
      (30.7%), hypotension (15.3%), full triad (15.3%) and asymptomatic patients at
      presentation were (30.7%). Ascitic fluid culture (by conventional methods) was
      positive in 46%. All the culture positive samples grew Gram-negative bacilli; E.
      coli being the most common microorganism (50%). Among five parameters (age,
      positivity of ascitic fluid culture, severity of CLD, presence of encephalopathy
      and lack of peritoneal irritation signs), only the increased age seems to be
      associated with higher in-hospital mortality.

PMID- 19861772
TI  - Biliary ascariasis: sonographic diagnosis.

PMID- 19861773
TI  - Adult celiac disease associated with type 1 diabetes.

PMID- 19861774
TI  - Meso-sigmoidcolon hamartoma.

PMID- 19861775
TI  - Hepatopulmonary syndrome.

PMID- 19861776
TI  - Serological profile of sporadic acute viral hepatitis in an area of hyper-endemic
      hepatitis B virus infection.
AB  - BACKGROUND: Located in the south western part of Saudi Arabia, the Gizan region
      is largely a rural community in which hepatitis B and chronic liver disease
      including hepatocellular carcinoma are highly prevalent. AIM OF STUDY: To
      determine the relative frequencies of acute hepatitis A, B, C and E in acute
      viral hepatitis in an area of hyperendemic hepatitis B infection. METHODS AND
      MATERIALS: In a prospective study 246 consecutive patients (179 males and 67
      females) diagnosed in a 2-year period were tested for markers of Hepatitis A
      virus (HAV), hepatitis B virus (HBV), hepatitis C (HCV) and hepatitis E virus
      (HEV). RESULTS: Of the patients tested, 131 (53.3%) were children ( < 10 years),
      and 42 (17%) were 11 - 20 years in age. Ig M anti -HAV, IgM anti-HBV, anti- HCV
      and IgM anti-HEV were positive in 37%, 19.1%, 3.7% and 13.7% respectively.
      Markers of these viruses were absent in 24.4%. Among 131 children (< 10 years)
      the commonest cause of AVH was HAV occurring in 57.3% of the cases. In adults (>
      21 years) HBV was found in 35.6% and IgM anti -HAV was detected in only 6.8%. In
      contrast to the age- related decline in the frequency of acute HA, the proportion
      of acute HE were similar in all age groups (13.7% in children, 16.7% in
      adolescents and 11.0% in adults). CONCLUSION: The study indicated that HAV is
      still a common cause of AVH particularly among children in Gizan. Acute 1-113 had
      a low occurrence among the children, evidently as a consequence of the
      integration of HB vaccine into the Saudi Arabian national EPI, 10 years ago. With
      the availability of combined HB and HA vaccines, It should be possible to graft
      the vaccination against HAV on to the existing program in Saudi Arabia. Affecting
      13.4% of the group studied, sporadic HEV constitute a significant cause of AVH in
      this population. Until HEV vaccine becomes widely available, its prevention would
      be mainly by the improvement of socio - economic and hygienic standards of the
      population.

PMID- 19861777
TI  - Duplication of hepatic artery.
AB  - BACKGROUND: The hepatic arterial anatomy is aberrant in almost 33-41% of
      individuals. The variant arterial anatomy recognized during routine cadaveric
      dissection offers great learning potential. Such findings provide an alternative
      perspective to view common morphology and its structural and functional
      importance. These impart the concept of patient individuality and subsequent
      individualization of medical and surgical therapies. Adequate knowledge of normal
      and abnormal arterial anatomy is essential for peripancreatic surgery and liver
      transplantation. AIMS OF THE STUDY: To report on hepatic artery variations
      observed in the dissecting room and to find out the macroscopic pattern of varied
      human hepatic arterial vascularization by cadaveric dissection. PATIENTS AND
      METHODS: Twenty human cadavers of caucasian origin were dissected to study the
      source and topographic pattern of hepatic arterial supply. RESULTS: Nineteen
      cadavers exhibited typical hepatic arterial supply from the celiac axis. Only one
      female body out of twenty cadavers exhibited a dual arterial supply to all parts
      of liver and gallbladder. One artery originated from the celiac axis whereas the
      other was given off by the superior mesenteric artery. CONCLUSION: No doubt,
      aberrant hepatic vascularization should be assessed preoperatively by invasive
      and noninvasive techniques to avoid fatal complications, but we favour careful
      dissection over angiography as a means of defining the arterial anatomy.

PMID- 19861778
TI  - Diverticular disease: an experience at King Faisal specialist hospital.
AB  - BACKGROUND: Diverticular disease of the colon is rarely seen in Saudi Arabia and
      this paper describes our experience with 16 patients admitted to hospital during
      an 8-year period (March 1990 - February 1998). PATIENTS AND METHODS: A
      computerized data base of patients having colorectal surgery was searched to
      identify patients admitted to the colorectal unit suffering from diverticular
      disease of the colon or it's complications. The records of these patients were
      examined and form the basis of this report. RESULTS: Sixteen patients were
      admitted to the colorectal unit for the management of diverticular disease or
      it's complications during an 8-year period. One patient presented with a
      localized abscess which was drained percutaneously. Fifteen patients underwent
      one or more surgical interventions. There were three female patients. One patient
      was referred for stoma closure, four for elective surgery and ten with acute
      perforation of whom one underwent right hemicolectomy for a perforated caecal
      diverticulum and nine underwent Hartmann's procedure for sigmoid perforation. Two
      patients required multiple abdominal washouts. Post-operatively two patients
      developed severe chest infections, one developed renal failure and two urinary
      infections. Four wounds became infected and two intra abdominal collections were
      drained percutaneously. No patient died. Eight stomata (89%) were subsequently
      closed. The mean duration of follow up was 2.7 yr. Four patients were lost to
      follow up. CONCLUSION: This small series documents the presence of diverticular
      disease and it's complications in the Kingdom of Saudi Arabia and suggests that
      the commonest method of presentation may be an acute one. Surgeons must thus be
      mindful of the condition and take appropriate action. Hartmann's' operation was
      safe and resulted in a low morbidity and no mortality. 89% of the stomata were
      closed at a later procedure.

PMID- 19861779
TI  - Large liver abscess: unusual presentation of fascioliasis: case report and
      literature review.

PMID- 19861780
TI  - Primary intestinal lymphangiectasia, nephrotic syndrome and clomid-induced
      triplet pregnancy.

PMID- 19861781
TI  - Ulcerative colitis and chronic granulomatous disease: a case report and review of
      the literature.

PMID- 19861782
TI  - Aminosalicylates.

PMID- 19861783
TI  - Hepatic encephalpathy: new concepts of pathogenesis, biological basis and
      outcome.

PMID- 19861784
TI  - Significance of normal liver enzymes in patients with hepatitis C virus.
AB  - BACKGROUND: Hepatitis C Virus (HCV) infection is a common universal problem
      especially in the Arab World. OBJECTIVE: To assess the significance of
      persistently normal liver enzymes in patients who were anti HCV positive and
      suggest the proper approach for this group of patients. METHOD: 56 patients who
      were anti HCV positive with persistently normal liver enzymes for more than one
      year underwent liver biopsy to assess their liver histology after excluding other
      possible causes of chronic liver disease. METAVIR scoring system was used and the
      degree of fibrosis (F0-F4) was considered as reflection of severity. RESULTS: Out
      of 56 patients, only 52 patients had liver biopsies; 44 (84.6%) patients had
      abnormal liver histology and eight (15.4%) patients had normal liver biopsy. Out
      of the 44 patients with abnormal liver biopsy, 23 (44.2%) patients had mild
      histology (F1-F2); 15 (28.8%) patients had severe histology (F3); two (3.8%)
      patients had cirrhosis (F4); four (7.7%) patients had non-specific changes
      (Al/FO). CONCLUSION: Normal liver enzymes in patients who were anti HCV positive
      does not carry prognostic implication and patients should have a liver biopsy to
      assess their liver histology, though the chance of having mild histology with
      minimal inflammation is more than 50%.

PMID- 19861785
TI  - Intracorporeal vicryl ligatures reduces cost in some countries.
AB  - BACKGROUND: Financial constraints and pressing priorities are major problems that
      delay implementation of laparoscopic cholecystectomy (LC) in some countries. This
      raised the need for improvisation and innovation. Endoclips are not available in
      some local markets. They cost $50 for a single set of six clips to import, in
      contrast to 2/0 polyglacin (Vicryl-Ethicon), which is available at a rate of $1.5
      for one thread. OBJECTIVE OF THE STUDY: To compare the safety and cost between
      vicryl ligature and endoclips. PATIENTS AND METHOD: To secure the cystic duct,
      intracorporeal vicryl ligature (IVL) was applied in 64 LCs. These were divided
      into 32 patients presented with cystic duct, which was too wide to controlled
      with endoclips (group A) and 32 patients with normal diameter of cystic duct as
      controls (group B). Also we describe the test we used to prove the safety of IVL
      in the two groups. This ligature was tested with high pressure introduced and
      measured into the gallbladder by sphygmomanometer. RESULTS: The gallbladder can
      withstand a mean (+ SD) pressure of 197 (+20.94) mmHg and 191.67 (+10.2) in group
      A and B respectively without statistically significant difference (P 0.1305).
      Total cost of vicryl was $128 compared to $3200 if endoclips were used. No
      complication was noted related to these ligatures in a period of two year-follow
      up. CONCLUSION: This method is easy, cost effective and suitable in some
      countries.

PMID- 19861786
TI  - Predictive factors for failure of endoscopic management therapy in peptic ulcer
      bleeding.
AB  - BACKGROUND: After endoscopic therapy for peptic ulcer bleeding, rebleeding occurs
      in up to 20% of patients. OBJECTIVE: The aim of this retrospective analysis was
      to identify the factors responsible for failure to achieve hemostasis or
      rebleeding after endoscopic therapy. METHODS: Seventy six patients who bled from
      peptic ulcers and received endoscopic therapy were identified in a retrospective
      analysis of six years, from 1993 to 1998, in a tertiary care hospital in Muscat,
      Oman. All patients were endoscoped within 24 hours and received endoscopic
      treatment, either injection of 1/10,000 adrenaline alone or both injection and
      thermocoagulation. We looked at the following factors, which could have
      influenced the outcome of endoscopic therapy. The clinical and endoscopic
      parameters used to assess the outcome of endoscopic therapy were: age, sex, blood
      pressure and hemoglobin on admission, number of units of blood transfused, use of
      NSAID, comorbid conditions, ulcer site, ulcer size. Forrest grade, injection
      alone and injection plus thermocoagulation. RESULTS: Endoscopic therapy failed in
      16 patients (21%). Twelve patients received a second endoscopic treatment, but 13
      patients eventually required surgery. Six patients died as a result of bleeding
      (mortality 8%). Among the parameters, hemoglobin on admission, more than six
      units of blood transfusion, shock, co-morbid diseases, ulcer site and size and
      Forrest grade la predicted the possibility of failure of endoscopic therapy.
      CONCLUSION: In patients presenting with peptic ulcer bleeding, hemoglobin less
      than 10 grams, more than six units of blood transfusion, shock on admission, co
      morbid disease, posterior wall duodenal ulcer, large ulcer size of > I cm size
      and Forrest la predicted failure of endoscopic therapy.

PMID- 19861787
TI  - Carcinosarcoma of the gallbladder: A case report and review of literature.

PMID- 19861788
TI  - Appendiceal intussusception of mucinous cystadenoma presenting as acute
      appendicitis.

PMID- 19861789
TI  - Malakoplakia in the appendix: unusual association with mucinous cystadenoma: case
      report and review of literature.

PMID- 19861790
TI  - Diseases of the appendix recognized during colonoscopy.
AB  - Although the appendiceal orifice is routinely identified during a total
      colonoscopic examination, there are only a few reports in the English literature
      describing abnormalities in this region. Many recent case reports have described
      endoscopic features of various appendiceal pathologies. In order to increase the
      awareness as well as facilitate the recognition of these uncommon encounters a
      review of the literature on the endoscopic features of various appendiceal
      problems is provided. The most frequently reported abnormalities are related to
      appendiceal neoplasms or intussusception. Interesting observations and new
      features of appendiceal regional abnormalities in acute appendicitis and
      ulcerative colitis are being described. Importance of appendiceal involvement in
      ulcerative colitis is of interest in particular. This may have impact on the
      disease prognosis and management. The knowledge of the emerging role of
      colonoscopy in the diagnosis and management of complicated appendicitis might
      encourage a more aggressive non-operative approach in some of these cases.
      Recognition of rare entities requires knowledge of their endoscopic appearance.
      Awareness of these new developments is essential for all endoscopists performing
      routine colonoscopic examination. In order to detect any abnormality, the
      appendiceal orifice should be carefully inspected during all routine colonoscopic
      examinations. This systematic approach may eventually result in more frequent pre
      operative diagnosis of appendiceal problems.

PMID- 19861791
TI  - Life events stress in ulcerative colitis: a case-control study.
AB  - BACKGROUND: Ulcerative colitis (UC) is significantly associated with life events
      stress. AIM: To investigate the relationship between ulcerative colitis, and life
      events stress. METHODS: A prospective study of 30 patients with ulcerative
      colitis and 30 healthy controls. A semi-structured psychiatric interview and
      clinical mental state examination were used in the psychiatric assessment of the
      patients and controls. Psychiatric diagnoses were made according to ICD-10. A
      modified version of Life Events Scale by Tennant and Andrews was used in the
      assessment of life events stress. RESULTS: Life events stress were significantly
      experienced by more patients than the controls. The total number of life events,
      the number of individual significant life events and the total number of
      unpleasant events were all significantly more in patients than the controls.
      CONCLUSIONS: In this study the association between the ulcerative colitis and
      life events stress is substantiated at all levels. However, further more
      extensive studies are needed to elucidate the nature of this relationship.

PMID- 19861792
TI  - Small bowel perforation after extracorporeal shockwave lithotripsy for ureteric
      stone: a case report and review of the literature.

PMID- 19861793
TI  - Perforation of jejunal diverticulum.

PMID- 19861794
TI  - Acute ileal tuberculosis perforation: a case report.

PMID- 19861795
TI  - Gastric asthma: a clinical review.
AB  - Gastroesophageal reflux (GER) is defined as the movement of gastric contents into
      the esophagus. This material, which may contain acid, pepsin, bile acids and
      pancreatic enzymes, has the ability to irritate or injure tissues not adapted to
      the presence of this potentially noxious material. As reflux may proceed more
      proximal than the esophagus, other tissues may he affected, both clinical and
      experimental data have demonstrated that these events nay lead to a variety of
      esophageal, head, neck and pulmonary complications. Pulmonary manifestations of
      GER have been the focus of the medical literature, for the last two decades, and
      in particular the association of GER and asthma has been well recognized. The
      latter was suggested first by Sir William Osler more than a century ago. Nowadays
      its presence is well known in terms of gastric asthma, but the importance is till
      a matter of debate. The prevalence of GER among patients with asthma is generally
      reported to be higher than in normal but with a wide range from 30% to 90% in
      several reports. The mechanism by which GER might induce asthma has been a
      subject of diversity. There are two potential mechanisms whereby GER could
      produce bronchoconstriction and therefore exacerbate airflow obstruction in
      asthmatics, the evidences for these mechanisms were reviewed in the text.

PMID- 19861796
TI  - Medical treatment of perianal Crohn disease.
AB  - Crohn disease is a chronic illness that affects the gastrointestinal tract from
      the mouth to the anus. Perianal Crohn develops in 31-94% of patients over the
      course of their illness. It affects the skin in the perianal area, the anal canal
      and can cause fistulae. It is diagnosed clinically and by other modalities like
      endoscopy, barium CT scan, endoscopic sonography and magnetic resonance image
      examination. The treatment of perianal Crohn disease is either medical or
      surgical. The current medical treatment will be reviewed in this article.

PMID- 19861797
TI  - Efficacy of hepatitis B vaccine in a cohortcommunity-based study in Riyadh and
      Hail regions of Saudi Arabia.
AB  - BACKGROUND: Saudi Arabia used to be hyperendemic for HBV infection. Most of
      infection occurs in early life. HBV vaccine was, therefore, introduced in 1989 as
      the seventh primary immunogen of the EPI Program. This study is conducted to
      evaluate the efficacy of this program in Riyadh and Hail Regions. METHOD AND
      PATIENTS: A cohort follow-up study of children from Riyadh and Hail, who had been
      vaccinated in 1989, evaluated in 1991 and tested for HBV markers six years later.
      RESULTS: The files of 303 children from Riyadh and Hail, who were investigated in
      1991 retrieved and only 119, were available for testing. Fifty percent of the
      children have still a protective anti-HBs tittre. One vaccinated child was found
      to be positive for HBsAg. According to this study, the efficacy rate against
      HBsAg carriage is 88%. CONCLUSION: This study demonstrates the tremendous effect
      of HB vaccine on the HBV infection of Saudi children in these two regions.

PMID- 19861798
TI  - Role of preoperative endoscopic retrograde cholangio pancreaticography in the
      management of mild to moderate acute biliary pancreatitis.
AB  - BACKGROUND: Controversy still exists about the role and timing of endoscopic
      retrograde cholangiopancreaicotography (ERCP) in mild to moderate biliary
      pancreatitis. Routine preoperative ERCP detects persisting common bile duct
      stones but is associated with definite morbidity and may delay definitive care.
      AIM OF STUDY: The study aims to evaluate the role of ERCP in the management of
      mild to moderate acute biliary pancreatitis. PATIENTS AND METHODS: The records of
      196 patients with diagnosis of mild to moderate acute biliary pancreatitis (ABP)
      were retrospectively reviewed over four-years period. The various parameters
      examined were age, sex, clinical presentation, laboratory values, radiological
      studies, and severity of the attack, preoperative ERCP, surgical intervention and
      length of hospital stay. Pre operative ERCP was performed in 136 (67%) patients.
      Indications of ERCP were presence of jaundice, dilated common bile duct on
      ultrasonography, persistent hyperamylasemia, and associated cholangitis. In 17
      patients with old age and multiple medical problems, ERCP served as a definite
      procedure. RESULTS: Mild to moderate cases accounted for 91% of ABP. Liver
      function tests (bilirubin, ALP, AST, ALT) were raised in 64% of cases. persistent
      hyperamylasemia in 4%, dilated CBD was observed in 14% associated cholangitis was
      present in 11%. Preoperative ERCP was positive in 22 (16%) patients, only where a
      CBD stones could be found and an endoscopic sphincterotomy) (ES) was performed.
      Positive predictive values were 25% for the high bilirubin level, 22% for the
      high ALP level, 50% for the persistent hyperamylasemia, 57% for the dilated CBD,
      45% for the associated cholangitis. ERCP was associated with a morbidity rate of
      3.6% with no mortality. The procedure was regarded as unnecessary in 84% of
      cases, where it increased the length of hospital stay by a mean of 2, 3 days.
      CONCLUSION: Preoperative ERCP was therapeutic in only 16% in cases of mild to
      moderate ABP. It should be done only on selective basis. In elderly patients with
      multiple medical problems. ERCP and ES can serve as definitive treatment.

PMID- 19861799
TI  - Colonoscopic removal of an appendiceal polyp.

PMID- 19861801
TI  - Cryptogenic or autoimmune hepatitis.

PMID- 19861800
TI  - Conservative management of traumatic pancreatic fistula.

PMID- 19861802
TI  - Perspective on the Saudi Council for Health Specialities.

PMID- 19861803
TI  - Diagnosis of regional enrteritis (Crohn disease).
AB  - Regional enteritis (Crohn disease) may present a diagnostic problem that needs to
      be solved by clinicians practicing in areas known to be endemic for tuberculosis.
      The similarity in clinical presentation between the two disorders makes it
      difficult to reach a diagnosis. Furthermore, the use of steroids in treating
      patients with Crohn disease may be harmful if the underlying diagnosis is
      Tuberculosis. This article is aimed to help physicians to distinguish Crohn
      disease from intestinal Tuberculosis. The treating physician would be able to use
      and interpret different diagnostic modalities tailored to the history and
      physical examination. The use of ASCA, a new serological marker, in the diagnosis
      of Crohn disease may facilitate the management of such patients.

PMID- 19861804
TI  - Budd Chiari syndrome: experience at King Faisal Specialist Hospital and Research
      Centre, Riyadh, Saudi Arabia.
AB  - BACKGROUND: Budd-chiari syndrome (BCS) is rare disorder, varied in etiology,
      inconsistent in presentation, unpredictable in progression, and challenging in
      therapy. AIM OF STUDY: The aim of this study is to review experience of Budd
      Chiari syndrome at KFSH, Riyadh; over a ten-year period. METHODS: In a
      retrospective study using a computer data search of the medical records from May
      1990 to May 2000, 43 patients' charts suspected of BCS were reviewed. 29 patients
      were found to have BCS, diagnosed by Doppler ultrasound, venography, MRI, or CT
      with or without liver biopsy. FINDINGS: Of the 29 patients, 18 were male (62.1%)
      and I 1 were female (37.9%); mean age was 35.4 (range 17-69 years). Nine patients
      had Behcet's disease; seven patients had malignancy (five HCC, one melanoma and
      one hypernephroma). Eight patients had antiphospholipid syndrome, two patients
      had no known cause and three (one related to trauma, the other related to protein
      C deficiency and the third related nephrotic syndrome). Nineteen patients
      presented acutely with abdominal pain, progressive ascites and hepatomegaly. Ten
      patients had subacute presentation mimicking cirrhosis of liver. Five patients
      had web in the intrahepatic IVC or ostium HV and the remaining 24 patients had
      thrombosis of hepatic veins. Five patients received surgical shunts, three had
      balloon dilatation of webs, 11 had anticoagulant therapy and seven patients had
      symptomatic treatment. Eleven patients died, six of them had malignancy, two died
      while awaiting liver transplantation and three died with fulminant hepatic
      failure. Fourteen patients are still on follow-up. CONCLUSION: Budd Chiari
      syndrome in Saudi Arabia is related to a defined cause in majority of patients
      (92%). Behcet's disease is a dominant cause of BCS in Saudi Arabia. This is in
      contrast to world literature where around 50% of patients are of unknown
      etiology.

PMID- 19861805
TI  - Gammaglutamyl transpeptidase activity in patients with schistosomiasis.
AB  - BACKGROUND: Schistosoma mansoni infestation may induce liver fibrosis and portal
      hypertension, with possible elevation of liver enzymes. AIM OF THE STUDY: The aim
      of this study was to evaluate the serum gammaglutamyl transpeptidase (GGT)
      activity in a group of non-alcoholic and non-obese patients with hepatointestinal
      schistosomiasis. PATIENTS AND METHODS: Medical records of 174 patients diagnosed
      to have hepatointestinal schistosomiasis on the basis of clinical and laboratory
      data were reviewed. Body mass index (BMI) was calculated for all patients. Direct
      stool smear and formol-ether concentration (FEC) methods and hematological and
      biochemical blood tests were performed. Other studies including abdominal
      ultrasonography, upper and lower gastrointestinal endoscopy was also performed
      when feasible. All (174) patients were adults with male to female ratio of 3.8:1.
      BMI was similar in both groups. Patients were divided into two groups: group 1
      (57) with elevated GGT and group 2 (117) patients with normal GGT. Both groups
      had positive indirect hemagglutination test (IHA) for schistosomiasis. Other
      causes of liver disease were excluded. RESULTS: Group 1 had significant elevation
      of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and reduction in
      platelets (p < 0.001), low albumin and high globulin levels (p < 0.01) compared
      to group 2. Abnormal ultrasonographic findings were more frequently encountered
      in group 1 (p < 0.001). CONCLUSION: The above data indicated that GGT elevation
      was most likely secondary to hepatobiliary involvement by Schistosoma mansoni and
      may indicate chronicity. Therefore schistosomiasis has to be considered in our
      community whenever GGT is elevated in non-alcoholic population.

PMID- 19861806
TI  - Splenic epithelial (epidermoid) cyst.

PMID- 19861807
TI  - Hepatoid gastric adenocarcinoma.

PMID- 19861808
TI  - The liver and the haemeostatic system.
AB  - The liver plays a central role in the control of haemostasis being the site of
      synthesis of most of the coagulation factors and natural anticoagulants, as well
      as fibrinolytic factors except the main activators of the fibrinolytic system (t
      PA and u-PA). The liver also clears many of the activated clotting and
      fibrinolytic factors, as well as haemostatic activation complexes (TAT and PAP)
      and end product of fibrin degradation, FDP. Therefore, liver disease results in a
      complex and multifactorial pattern of defects in haemostatic function in the form
      of: (i) decreased synthesis of coagulation factors (ii) Abnormal protein
      synthesis e.g. dysfibrinogen (iii) Deficiency of natural anticoagulants (iv)
      Enhanced fibrinolytic activity (v) Quantitative and qualitative platelet defects
      (vi) Consumptive coagulopathy as in advanced liver disease. These abnormalities
      of haemostasis, which often occurs in the form of multiple defects, underlie the
      haemorrhagic diathesis, which often complicates liver disease. In the same
      manner, measurement of various haemostatic factors can be employed to reflect the
      degree of liver damage.

PMID- 19861809
TI  - Treatment of chronic hepatitis B in Oman experience with lamivudine.
AB  - BACKGROUND: Chronic hepatitis B (CHB) in Oman is similar to the Mediterranean
      Region with significant number of HBeAg negative patients. Interferon therapy is
      less effective in these patients and lamivudine is an alternative treatment.
      PATIENTS AND METHODS: Thirty patients (16 HBeAg positive), who received
      lamivudine were studied retrospectively over 27 months. End of treatment (after
      52 weeks) and sustained responses were analyzed for both HBe-antigen positive and
      negative patients. RESULTS: Of the thirty patients, who received lamivudine, 22
      patients (73%) completed 52 weeks therapy. Eight patients had previously received
      interferon treatment. The overall end-of-treatment (ET) biochemical response was
      81.8% and virological response was 45%. Among patients who were HBeAg positive
      and HBeAg negative, similar proportion of patients achieved end-of-treatment
      biochemical responses (80% Vs 83.3%) and virological responses (40% Vs 50%)
      respectively. Sustained biochemical and virological response was achieved in four
      patients, two each in both groups. Of the nine patients currently receiving
      treatment, six of them had normalization of ALT and two had undetectable HBV DNA.
      CONCLUSION: Almost 50% of patients with CHB in Oman have HBeAg negative
      hepatitis. Therapy with lamivudine is effective in both HBeAg positive and
      negative cases.

PMID- 19861810
TI  - The significance of elevated serologic markers of celiac disease in children with
      juvenile rheumatoid arthritis.
AB  - AIM: The aim of this study is to determine the frequency of celiac disease (CD)
      in a group of children with juvenile rheumatoid arthritis (JRA) and determine the
      correlation between the presence of the serologic markers and the histological
      diagnosis of CD. PATIENTS AND METHODS: Forty-two children (24 females) with JRA,
      aged between 5-15 years underwent study of serologic markers for CD (gliadin-IgA,
      gliadin-IgG, reticulin and endomysium-IgA antibodies). Endoscopic intestinal
      biopsy was performed in patients who had positive serologic markers for CD. The
      diagnosis of CD was based on the classic finding of villous atrophy and crypt
      hypertrophy. RESULTS: Eighteen patients (42.8%) had serologic markers for CD; ten
      of them with a systemic form, five with a polyarticular form and three with a
      pauciarticular form of JRA. Levels of AGA -IgG were high in 14 patients (77.8%),
      four patients (22.2%) had high levels of AGA-IgA and seven patients (38.9%) had
      anti-endomysium antibodies (AEA). One patient had anti-reticulin antibodies (ARA)
      5.5%. Sixteen patients underwent intestinal biopsy; in only one patient with AEA
      antibodies (2.38%), biopsy revealed typical finding of CD. The patient with CD
      showed improvement in both growth parameter as well as articular symptoms after
      starting gluten-free diet CONCLUSION: Our study shows that the screening for
      silent CD among children with JRA may be useful. Those patients with AEA need
      further follow up since these antibodies are quite sensitive and specific for CD.

PMID- 19861811
TI  - Multicentric leiomyosarcoma of the stomach.

PMID- 19861812
TI  - Rare presentation of Budd-Chiari syndrome.

PMID- 19861813
TI  - Spontaneous splenic rupture in infectious mononucleosis.

PMID- 19861814
TI  - Honey potentiates the gastric protection effects of sucralfate against ammonia
      induced gastric lesions in rats.
AB  - BACKGROUND: Natural honey is widely used all over the world as a complementary
      and alternative medicine in various disorders including gastrointestinal lesions.
      AIM: To evaluate the effects of combination of low dosage of honey (0.312 g/kg)
      and sucralfate (0.125 or 0.250 g /kg) on gastric protection and to determine any
      potentiating interactions between them against ammonia-induced gastric lesions in
      rats. MATERIAL AND METHODS: Twenty-four hours fasted rats were given I ml of
      ammonium hydroxide 1 % intragastrically and they were killed one hour later under
      deep ether anesthesia. The gastric lesion index was calculated according to the
      method of Takaishi et al 1998. Non protein sulthydryls level was determined
      spectrophotometrically as described by Sedlak and Lindsay 1968. RESULTS:
      Administration of ammonium hydroxide produced red and black linear lesions and
      significant depletion of gastric nonprotein sulthydryls level. Oral
      administration of honey (0.312g/kg) or sucralfate (0.125 and 0.250 g/kg) 30 min
      before ammonium hydroxide reduced the severity of gastric mucosal lesions by 1 I
      or 18 and 42 % respectively, and has shown the changes in nonprotein sulfhydryls
      level induced by ammonium hydroxide. Furthermore, pretreatment with a combination
      of a low dose of honey (0.312 g /kg) and sucralfate (0.125 g or 0.250 g/kg)
      afforded significantly greater protection (58 and 77 %) than that obtained with
      either of them administered alone. CONCLUSION: The present results suggest
      potentiation of gastric protection effect of sucralfate by honey and this may
      have a clinical value in the treatment of peptic ulcer diseases in Helicobacter
      pylori positive patients.

PMID- 19861815
TI  - Laparoscopic cholecystectomy: the outcome with minimal conversion rate:
      experience in a district hospital.
AB  - BACKGROUND: Since introducing laparoscopic cholecystectomy (LC) different centres
      have reported different conversion rate (CR) to open cholecystectomy (OC) and
      different reasons for conversion. OBJECTIVE: To evaluate the role of LC in the
      treatment of symptomatic gallstones and establish the outcomes of this treatment
      modality in general, looking especially into the rate of conversion to OC, at a
      district hospital. PATIENTS AND METHODS: From July 1992-July 1998, 751 patients
      who underwent LC were retrospectively reviewed. All patients with symptomatic
      gallstones were offered LC with no exclusion criteria apart from anaesthetic
      opinion. No attempts were made at selection of patients for LC. RESULTS: There
      were 751 patients with symptomatic gallstones (617 females, 134 males) underwent
      LC. Chronic cholecystitis represented the majority of cases (83%). The mean
      operative time was 65.52 minutes: pre-operation and main hospital stay was 2.46
      days. Our total conversion rate was 0.9% and 0.4% if malignancy of the
      gallbladder is excluded. In comparison to the published data, there was obvious
      lower conversion rate, which was neither associated with increased morbidity nor
      mortality. CONCLUSION: Laparoscopic cholecystectomy is a reliable, safe and cost
      effective treatment modality for symptomatic gallstones. With growing experience
      in laparoscopic technique, proper settings and harmony of the operating team, it
      is possible to bring the conversion rate to OC to the minimum without any
      increment in mortality or morbidity.

PMID- 19861816
TI  - Interferon-ribavirin therapy for chronic hepatitis C: efficacy in Saudi patients.
AB  - BACKGROUND: Hepatitis C affects 2% of Saudi population. Previous local trials
      showed low response to interferon monotherapy for six-months. AIM: To evaluate
      biochemical and virological response of interferon-ribavirin combination on naive
      Saudi patients infected with HCV. METHODS: A prospective single armed study was
      conducted at Riyadh Armed Forces Hospital from July 1999 to July 2002 for fifty
      patients who have hepatitis C virus (HCV-PCR) positive and chronic hepatitis on
      liver biopsy were started on the combination therapy for one-year. All had HCV
      PCR at the end of therapy and at six months follow-up. RESULTS: Thirty-one
      patients (62%) normalized their ALT levels, and 25 patients (50%) became HCV-PCR
      negative achieving end-of-treatment response (ETR). The sustained virological
      response (SR) was achieved in 19 patients (38%) at six months follow-up after
      stopping the treatment. Side effects were mainly flu like syndrome in 36 patients
      (72%). CONCLUSION: Combination therapy of interferon alfa-2b plus ribavirin is an
      effective treatment modality for HCV infected Saudi patients, with tolerable side
      effects. Our virological response rates are compatible with international
      published literatures.

PMID- 19861817
TI  - Management of complicated gallstone disease during pregnancy.
AB  - BACKGROUND: Controversy still exists regarding the optimal management of
      complicated gallstones during pregnancy owing to the possible risks for the
      fetus. Generally the management of such problems during pregnancy is
      conservative, however, endoscopic retrograde cholangiopancreatography (ERCP)
      and/or operative intervention may be required in some patients. AIM OF STUDY: The
      aim is to evaluate the management of complicated gallstone disease with
      particular reference to the indications, timing and risks of ERCP and operative
      intervention during pregnancy and its effect on fetus outcome. PATIENTS AND
      METHODS: This retrospective study was conducted on 32 pregnant women, who were
      admitted with complication of cholelithiasis at Riyadh Medical Complex (RMC)
      through the emergency during the period of March 1998-October 2002. Their files
      were evaluated for age, presentation, gestational age, hematological,
      radiological, fetus assessment, management, fetus out come and how ERCP and
      surgery were performed. RESULTS: Among the 32 pregnant women studied, 22
      responded satisfactorily to conservative treatment. They had laparoscopic
      cholecystectomy (LC) after delivery. Ten patients needed further treatment, two
      were operated for acute cholecystitis (AC) and recurrent biliary colic (BC).
      Eight patients had ERCP for obstructive jaundice and recurrent pancreatitis
      following which two had LC cholecystectomy. All patients remained well until
      delivery. CONCLUSION: Majority of gallstone complications during pregnancy can be
      managed conservatively. Surgery can be deferred until delivery. Few patients who
      needed ERCP and/or surgery can be managed safely during second and third
      trimester.

PMID- 19861818
TI  - Undifferentiated (embryonal) sarcoma of the liver: case report and review of the
      literature.

PMID- 19861819
TI  - Hepatocellular carcinoma and gall bladder adenocarcinoma: two primaries with no
      significant risk factors.

PMID- 19861820
TI  - Caecal lipoma causing colo-colonic intussusception.

PMID- 19861821
TI  - Wandering spleen.
AB  - Wandering spleen is a rare clinical entity, characterized by splenic
      hypermobility that results from elongation or maldevelopment of its suspensary
      ligaments. The wandering spleen is in constant danger of torsion and infarction.
      This condition poses a great diagnostic challenge due to lack of awareness and
      paucity of symptoms. Among adults, it usually occurs in females of childbearing
      age, the children below ten years of age are other sufferers. The clinical
      presentation may be acute or chronic; such as asymptomatic abdominal mass, an
      acute abdomen, or, most commonly, a mass associated with vague abdominal
      symptoms. Computed tomography and duplex ultrasonography are best diagnostic
      modalities. The traditional conservative approach carries high risk of infarction
      leading to splenectomy and postsplenectomy sepsis. Splenopexy is the treatment of
      choice for all noninfarcted wandering spleens. Splenectomy should only be
      performed when there is no evidence of splenic blood flow after detorsion of the
      spleen. The present study, reviews the presentation, course, diagnostic
      modalities and management options of wandering spleen.

PMID- 19861822
TI  - Management of postlaparoscopic cholecystectomy major bile duct injury: comparison
      of MRCP with conventional methods.
AB  - BACKGROUND: Postlaparoscopic cholecystectomy bile duct injury remains one of the
      devastating complications seen in current surgical practice. AIM OF STUDY: This
      study describes the diagnostic role of magnetic resonance
      cholangiopancreatography (MRCP) in such injuries compared with conventional
      methods. PATIENTS AND METHODS: Eighteen patients referred to the Division of
      Hepatobiliary Surgery, King Khalid University Hospital from July 1998 to
      September 2000 were retrospectively studied. The technique of the repair was by
      utilizing Roux-en-Y hepaticojejunostomy with establishment of mucosa-to-mucosa
      anastomosis.The study included presentation, age and gender. RESULTS: The
      presentation of patients were variable and frequently included pain, jaundice
      with or without cholangitis in 13 patients, bile leakage with development of
      biliary peritonitis in three, and development of external biliary fistula in two
      patients. Besides lower incidence of complication, MRCP was more diagnostic and
      informative in planning surgery by mapping both ducts proximal and distal to site
      of injury or stricture in 14 out of 18 patients. The Bismuth level of bile duct
      injuries were type I in one, type 11 in five, type III in 11 and type IV in one
      patient. All patients are alive, well and no complications occurred in the
      immediate postoperative period. Only two patients developed stricture within four
      months after surgery, one of them treated conservatively with repeated dilatation
      and stenting was done for the other. CONCLUSION: Hepaticojejunostomy is the
      procedure of choice for repair of bile duct injuries and provides adequate
      bilairy drainage. MRCP is an ideal diagnostic test when bile duct injury is
      suspected following laparoscopic cholecystectomy.

PMID- 19861823
TI  - The frequency of upper gastrointestinal malignancy in Gizan.
AB  - BACKGROUND: Upper gastrointestinal malignancy occurs in variable frequencies
      among different populations and there is an increasing epidemiological data in
      The Kingdom of Saudi Arabia. AIM OF THE STUDY: To determine the frequency of
      upper gastrointestinal malignancy in an endoscopic population in Gizan. PATIENTS
      AND METHODS: A retrospective analysis of 63 patients who had esophageal or
      gastric malignancy among 2572 patients evaluated in a 6-year period ( July 1992
      to June 1998) at King Fahad Central Hospital in Gizan. RESULTS: Esophageal cancer
      was found in 39 patients (20 males and 19 females), whereas gastric malignancy in
      24 (22 males and two females). The majority of the patients were in their seventh
      and eighth decade of life with male predominance. Seven patients had primary
      gastric lymphoma and one patient had primary malignant melanoma of the esophagus.
      CONCLUSION: Upper gastrointestinal malignancy represented 2.4% of 2572 endoscoped
      patients, occurring more commonly among elderly male.

PMID- 19861824
TI  - Ulcerative colitis: Al-Gassim experience.
AB  - BACKGROUND: Ulcerative colitis (UC) is being reported more frequently among the
      Arabs. Information on the clinical severity, endoscopic and histological grading
      is scanty. AIM: To assess the severity of the disease and its response to therapy
      in patients referred to a tertiary care referral centre in Gassim region, Kingdom
      of Saudi Arabia (KSA). PATIENTS AND METHOD: Hospital records of thirty-four
      patients found to have UC from 1990-2002 were analyzed. The study included
      clinical severity, endoscopical and histological assessment, response to therapy
      and frequency of complications. RESULTS: There were 21 males and 13 females with
      median age 35 (range: 18-76) years. The disease was clinically mild in seven
      patients (21%), moderate in 11 (32%) and severe in 16 (47%). Endoscopically UC
      was graded as 2 in three patients (9%), 3 in 21 patients (59%) and 4 in ten
      patients (29%). Histologically UC was mild to moderate in 11 patients (32%) and
      severe in 23 (68%). Extent of UC was total in nine patients (26%), up to
      transverse colon in six (18%), splenic flexure in 14 (41%), rectosigmoid region
      in four (12%) and only up to the rectum in one (3%). Twenty-nine patients (85%)
      were treated with salazopyrine and five patients (15%); (two of them were
      hypersensitive to salazopyrine) received 5-aminosalicylic acid. Proctocolectomy
      was performed in two with a focus of malignancy. No patient died during the
      median follow-up period of 48 months (range: 4 months to 12 years). CONCLUSION:
      Ulcerative colitis presented with varying severity, more frequently in males in
      the population studied. Most of the patients responded to salazopyrine and
      surgery was necessary when malignancy was detected.

PMID- 19861825
TI  - Solid and cystic papillary epithelial neoplasm of the pancreas.

PMID- 19861826
TI  - Herbal-induced dysphagia by granules containing starch and morphine.

PMID- 19861827
TI  - An unusual cause of acute abdomen in an adolescent.

PMID- 19861828
TI  - Concepts in leptin and liver disease.
AB  - Leptin is a cytokine l6kd peptide hormone. Its crucial role is regulation of
      appetite and the body fat mass mainly through action on the hypothalamus. It is
      produced mainly in adipocytes of white fat, as well as from other tissues e.g.
      placenta, skeletal muscles, fundus of the stomach and activated hepatic stellate
      cell (HSC) and recently reported that leptin is produced from B cell of islands
      of the pancreas. The gene responsible for production is present on chromosome 7
      called obse gene (ob/gene). Leptin receptors (OB-R) were present in two forms
      short (OB-Ra or OB-RS) and long one (OB-Rb or OB-RI). The main action of leptin
      depends on long form (OB-Rl), where very little evidence is available implicating
      a role for the short form in the action of leptin. One of the unconventional
      areas in which leptin is now receiving great attention is liver diseases as
      several published studies indicate that circulating leptin level are increased in
      cirrhosis, hepatitis C virus (HCV) and non-alcoholic steatohepatitis (NASH).

PMID- 19861829
TI  - Bilateral paravertebral block in advanced schistosomal liver disease: a
      prospective study.
AB  - BACKGROUND: Surgery in patients with schistosomal liver disease is usually
      associated with high risks of morbidity and mortality. Bilateral paravertebral
      block (BPVB) has been advocated as a useful technique for ventral abdominal
      hernias' repairs. AIM OF THE STUDY: To compare the efficacy of BPVB with general
      anesthesia (GA) for anterior abdominal wall hernias in advanced schistosomal
      liver disease patients. PATIENTS AND METHODS: Sixty patients were randomly
      allocated into two groups to receive either GA or BPVB. Variables were hospital
      stay, hemodynamic stability, postoperative nausea and vomiting (PONY),
      postoperative pain measured on a visual analogue scale (VAS) with assessment of
      the hepatic cell integrity using glutathione S transferase alpha (GSTA) and other
      liver enzymes. RESULTS: The main significant finding was an apparently
      significant shorter length of hospital stay following BPVB as compared with GA in
      patients (P 0.005). CONCLUSIONS: BPVB was superior to GA following abdominal
      ventral hernia repair in schistosomal liver fibrosis patients.

PMID- 19861830
TI  - Does Helicobacter pylori infection in chronic renal failure increase the risk of
      gastroduodenal lesions? A prospective study.
AB  - BACKGROUND: Helicobacter pylori (H.pylori) plays an important role in
      gastroduodenal disease. However, there are few data concerning the epidemiology
      of H.pylori in patients with chronic renal failure and on hemodialysis (HD)
      treatment. AIM OF THE STUDY: This study is aimed to determine the epidemiology of
      H.pylori infection in patients with end stage renal disease (ESRD) on
      Hemodialysis (HD). PATIENTS AND METHODS: Ninety-six patients with dyspeptic
      complaints were included in the study. They were divided into two groups; group
      one consisted of 46 patients with ESRD on HD and group two (control) of 50
      patients without renal disease. All patients were subjected to upper
      gastrointestinal endoscopies, and gastric biopsies were obtained for histological
      evidence of H. pylori infection. RESULTS: The mean age of both groups was
      similar. The prevalence of H.pylori among the two groups was not significantly
      different (45.7% Vs 48%=p > 0.05). The prevalence of duodenal ulcers was
      significantly higher in H.pylori positive than in H.pylori negative ESRD patients
      (p < 0.05). GERD was significantly lower in H.pylori positive patients in both
      groups (p < 0.001 and p < 0.01 respectively). CONCLUSION: This study showed a
      similar prevalence of H.pylori infection in both groups. H.pylori infection in
      patients with ESRD is probably associated with increased risk of gastroduodenal
      lesions.

PMID- 19861831
TI  - Alvarado score as an admission criterion for suspected appendicitis in adults.
AB  - BACKGROUND: Acute appendicitis is a common surgical problem. AIM OF THE STUDY: To
      assess Alvarado score as an admission criterion for adult patients with suspected
      appendicitis in order to decrease unnecessary admissions to surgical wards.
      PATIENTS AND METHODS: A prospective study of consecutive patients attending the
      Emergency Department (ED) of Riyadh Medical Complex with suspected appendicitis.
      The patients were managed according to the algorithm of the study protocol and
      discharged after clinical improvement either from ED or from the ward. They were
      followed by telephone 2-3 days later. Alvarado score was obtained in the ED in
      all patients. RESULTS: The study included 211 patients, 60 patients were observed
      in ED and discharged, 151 patients were admitted and 137 of them were operated
      with a negative rate of 12.5%. The remaining 14 patients were observed and
      discharged. No patients with a score of 4 or less had appendicitis. CONCLUSION:
      Though the diagnosis of acute appendicitis remains mainly clinical, Alvarado
      score can be recommended as a helpful tool for the admission criteria and further
      management in order to reduce unnecessary admissions and to reduce the morbidity
      and mortality of acute appendicitis.

PMID- 19861832
TI  - Fibrolamellar hepatocellular carcinoma with alpha-one antitrypsin liver disease.

PMID- 19861833
TI  - Enterolithiasis.

PMID- 19861834
TI  - A typical adult celiac disease: report of cases and review of the literature.

PMID- 19861835
TI  - Hepatitis C virus infection in Saudi Arabia.
AB  - Infection with hepatitis C virus (HCV) is a common global cause of chronic liver
      disease, which is also true in Saudi Arabia. HCV prevalence in Saudi Arabia
      varies in different provinces being highest in the Western and Southern
      provinces. Most of the studies among blood donors documented a decrease in HCV
      prevalence, probably due to increase awareness and improved socioeconomic status.
      Genotype 4 is the commonest genotype in Saudi patients infected with HCV which
      unfortunately is least likely to respond to the standard interferon therapy
      though recent studies using pegylated interferon demonstrated promising results.
      Liver transplantation for patients with end stage liver disease was started in
      1994 but the cases currently done are still less than that required.

PMID- 19861836
TI  - The association of Helicobacter pylori infection with coronary artery disease:
      fact or fiction?
AB  - Helicobacter pylori (H. pylori) infection is an important cause of peptic ulcer
      disease and other gastrointestinal disorders. Since its discovery, a number of
      extra-gastrointestinal diseases have been reported to be associated with H.
      pylori infection. Recently, several epidemiological and clinical studies
      suggested that H. pylori infection has been associated with an increased risk of
      developing coronary artery disease (CAD). Evidence from animal studies showed
      that H. pylori plays an important role in the acute phase of myocardial
      infarction by causing platelet aggregation and inducing pro-coagulant activity in
      experimentally infected mice. However, results from human studies are conflicting
      in providing clear evidence for an association between H. pylori and CAD.
      Therefore, the aim of this article is to critically analyze the available
      evidence to prove or refute such an association.

PMID- 19861837
TI  - Salmonella carriers among expatriate workers in Al-Qatif area.
AB  - BACKGROUND: Salmonella infection and diarrhoeal diseases are major causes of
      morbidity and mortality in the developing world. All expatriates applying for
      work permits in the Kingdom of Saudi Arabia (KSA) have to undergo a governmental
      compulsory health check program. AIM OF THE STUDY: To estimate the number of
      salmonella carriers who had previously been diagnosed as free of infection.
      SUBJECTS AND METHODS: Over a period of two years, a total of 17, 918 workers in
      Al-Qatif area, in the Eastern Province were tested for salmonella on stool
      samples. RESULTS: Three hundred and twenty eight were found to be asymptomatic
      carriers of salmonella. The highest frequency was found among workers from Egypt
      (13.1 %) while Filipinos and Indians were the lowest carriers (1.2%). Salmonella
      serogroups E, C 1 and C2 were most common ( 29%, 29% and 23.5% respectively)
      followed by serogroups B, D and C (13%, 3.7% and 1% respectively). No Shigella
      species were isolated. All carriers were given antibiotics and were instructed in
      prophylactic hygiene measures. After completing the course of antibiotics, they
      were retested and found to be clear of infection. CONCLUSION: The health check
      system in this area will contribute towards the prevention of outbreaks of
      infection by salmonella.

PMID- 19861838
TI  - Outcome of pancreaticoduodenectomy: comparing the classic Whipple with pyloric
      preservation.
AB  - BACKGROUND: The majority of patients presenting with periampullary neoplasms are
      operative candidates and are treated surgically. AIM OF THE STUDY: To assess the
      complications, morbidity, mortality and 2-year survival rates, and safety of
      pancreaticoduodenectomy for periampullary carcinomas in a non-oncology surgical
      set-up. PATIENTS AND METHODS: Records of 23 patients underwent
      pancreaticoduodenectomy for periampullary cancers between July 1995 and April
      2001 in Guilan, Iran, were reviewed. RESULTS: Among 23 consecutive patients who
      underwent pancreaticoduodenectomy, 16 were men and 7 were women, and the mean age
      was 58 +/-10.2 years. All the patients had a malignant neoplasm. Mean operative
      time was 7.3 hours. The surgical procedure was pylorus-preserving
      pancreaticoduodenectomy (PPPD) in 65%. The median intraoperative blood loss was
      625 ml and no transfusion was required. There was no intraoperative mortality,
      and the overall 30-day postoperative mortality rate was 4.5%. Delayed gastric
      emptying was the most common postoperative complication. The 2-year survival
      rates for periampullary cancers were 93% in PPPD and 62.5% in classic Whipple
      procedure. CONCLUSION: Pancreaticoduodenectomy for periampullary tumors remains a
      formidable procedure in our set-up. It can be performed safely with low mortality
      and morbidity rates.

PMID- 19861839
TI  - The completeness rate of colonoscopy in a cohort of unsedated patients.
AB  - BACKGROUND: Colonoscopy is considered a painful procedure requiring routine
      intravenous sedation, however there are number of potential advantages to
      performing colonoscopy without sedation. The aim of this study was to determine
      the effect of unsedated colonoscopy on the success rate of caecal intubation.
      PATIENTS AND METHODS: All charts of patients who had unsedated colonoscopy from
      January 2002 to September 2003 were reviewed. Patient characteristics including
      age, gender, and mode of presentation were collected. The success rate of
      unsedated colonoscopy was compared with the standard success rate of sedated
      colonoscopy in the literature. The reasons for incomplete colonoscopy and sites
      reached were recorded. RESULTS: During the study period, 503 examinations were
      performed. Patients mean age was 48.5 years, 55.9 % of them were males. Colonic
      polyps were the predominant abnormal endoscopic finding; occurring in 21.3%. The
      completion rate in the study population excluding patients with obstructive
      disease and patients with inadequate preparation was only 67%. CONCLUSION: In
      this cohort study, sedation probably affects the overall success rate of cecal
      intubation. A large prospective randomized study comparing sedated with unsedated
      colonoscopy in terms of completion rate and patient satisfaction is needed.

PMID- 19861840
TI  - Gallbladder perforation: a case report and review of the literature.

PMID- 19861841
TI  - Omental infection secondary to blunt trauma in a child.

PMID- 19861842
TI  - Diagnosis and treatment of viral liver fibrosis.
AB  - This review summarized the diagnostic value of fibrosis biomarkers and the
      efficacy of anti-viral treatments on fibrosis progression. Non-invasive
      biomarkers can facilitate the screening and management of chronic hepatitis C and
      B. Screening for significant fibrosis is-mandatory as very effective anti-viral
      treatments are available, permitting to stop or to reduce the fibrosis
      progression. The reduction of fibrosis progression will decrease the mortality
      due to complications of cirrhosis. In patients with chronic hepatitis C,
      pegylated interferons combined with ribavirin are effective in reducing fibrosis
      progression. In patients with chronic hepatitis B, lamivudine, adefovir and
      pegylated interferon are also effective in reducing fibrosis progression. In
      patients with chronic hepatitis Delta, pegylated interferon is also effective in
      reducing fibrosis progression.

PMID- 19861843
TI  - A review of gastrointestinal manifestations of Brucellosis.
AB  - Brucellosis is hyperendemic in the Kingdom of Saudi Arabia (KSA) with more than
      8,000 cases reported each year to the public health authorities. The disease can
      affect almost any organ system in the body including the gastrointestinal system.
      In some instances, gastrointestinal manifestations may be the only presenting
      features of the disease. These range from milder complaints like diarrhea,
      vomiting to more serious complications like involvement of the liver, the spleen
      and the gallbladder to rarely life-threatening complications like colitis,
      pancreatitis, peritonitis and intestinal obstruction. Recognition of this type of
      presentation of brucellosis is important because early diagnosis and treatment
      usually result in complete recovery without complications.

PMID- 19861844
TI  - Angiogenic effects of leptin in patients with nonalcoholic steatohepatitis.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is characterized by morphological
      features indistinguishable from alcoholic hepatitis in individuals who do not
      consume excess alcohol. The role of leptin in the development of NASH is claimed
      to be through its inflammatory, fibrogenic and angiogenic effects. AIM OF THE
      STUDY: to evaluate the leptin status in patients with NASH with the emphasis on
      its angiogenic effects and its relation to basic fibroblast growth (BFGF).
      PATIENTS AND METHODS: This study was conducted on twenty-five patients with NASH
      and twenty normal persons of matched age and sex as control. For both groups,
      lipid profile, fasting and postprandial blood glucose, Serum leptin and BFGF were
      determined. All the results were tabulated and statistically evaluated. RESULTS:
      Obesity, hyperlipidaemia and diabetes mellitus were prevalent among patients with
      NASH. There were significant increase of leptin and basic fibroblast growth
      factor in patients with NASH, as compared to control. CONCLUSION: Leptin plays an
      important role in the pathogenesis of NASH through its metabolic, fibrogenic and
      angiogenic effects. It may also have a role in the development of complications.

PMID- 19861845
TI  - Colonoscopy in children.
AB  - BACKGROUND: Pediatric colonoscopy is routinely performed in most hospitals in
      Saudi Arabia and yet published data are scarce. The objective of this report is
      to describe our experience in the practice of pediatric colonoscopy in Saudi
      Arabia. PATIENTS AND METHODS: Retrospective analysis of data of all patients
      below 18 years of age who underwent colonoscopy over a 10-year period. RESULTS:
      From 1414 H (1993 G) to 1423 H (2002 G), two hundred and seventeen colonoscopies,
      of which 183 diagnostic procedures, were performed on 183 children. The majority
      (94%) were Saudi nationals, the age range was between 5 months and 18 years, and
      the female to male ratio was 1:0.8. Colonoscopy was total in 58 (32%) and limited
      in 125 patients (68%). The commonest reason for not completing the procedure was
      securing the diagnosis in 45/125 patients (36%). The commonest indication was
      rectal bleeding (35%). The highest yield was in children with bloody diarrhea
      (91%) and the lowest in those with abdominal pain (27%) with an overall yield of
      44%. Colitis was the most common diagnosis occurring in 66% of the children.
      CONCLUSION: this report highlights the role of colonoscopy in the recognition of
      diseases of the colon in our community and identifies some of the problems areas
      associated with the performance of this procedure in our institution.

PMID- 19861846
TI  - The use of 0.2% glyceryl trinirate oinment for anal fissures.
AB  - AIM OF THE STUDY: To assess the clinical efficacy of 0.2% glyceryl trinitrate
      ointment in the management of acute and chronic anal fissures. PATIENTS AND
      METHODS: A prospective clinical study conducted on consecutive patients presented
      to the surgical clinic of King Khalid University Hospital, Riyadh with acute and
      chronic anal fissures, from January to December 2003. These patients were treated
      with topical 0.2% glyceryl trinitrate paste in soft white paraffin three times a
      day. Patients were examined at regular intervals to evaluate the fissure status,
      adverse reactions, symptomatic control and recurrence. RESULTS: This study
      comprised 121 patients, six of them were lost to follow-up and 109 (94.7%) of the
      remaining 115 patients were cured. Of those cured, 13 patients (11.3%) presented
      with acute and 102 (88.7%) with chronic fissures. There were 98 male and 17
      female patients with median age of 41 years (range, 14-70 years). Complete
      symptomatic relief was achieved in all patients within one month of therapy. Two
      patients, with chronic anal fissures presented with recurrent symptoms within one
      month of the completion of therapy both of them were successfully treated with
      repeat glyceryl trinitrate course. Treatment had to be terminated in six (5.2%)
      patients: five (4.3%) experienced intolerable adverse effects and one (0.8%)
      patient failed to respond. All these patients were successfully treated with
      lateral internal sphincterotomy. No patient complained of change in continence.
      CONCLUSION: Glyceryl trinitrate ointment produces adequate symptomatic control
      and healing of the anal fissures and can be considered as one of the recommended
      treatment options.

PMID- 19861847
TI  - Endometriosis of the appendix: a trap for the unwary.

PMID- 19861848
TI  - Neutrophil expression and infiltration into Crohn's intestine.
AB  - Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) of unknown
      etiology. The main pathological feature of IBD is transmural infiltration of
      polymorphonuclear neutrophils (PMN) and mononuclear cells associated with smooth
      muscle cell proliferation, accumulation of collagen, thickening and stenosis.
      While the etiology of Crohn's disease remains unknown, increased levels of
      proinflammatory cytokines, such as IL-1, IL-6, IL-8 and TNF in the inflamed bowel
      probably play a major role in the tissue injury and fibrosis that ensue. PMNs
      infiltrate into tissue in response to chemotactic signals produced by the tissue,
      such as a-chemokines (IL-8). Although, the initial infiltration of neutrophils is
      beneficial to kill foreign particles and bacteria, persistent infiltration causes
      tissue damage. This review shows some evidence of neutrophil expression in
      Crohn's bowel and the process of neutrophil infiltration into the inflamed
      tissue.

PMID- 19861849
TI  - Partial posterior wrap (toupet)in patients with defective esophageal body
      motility.
AB  - BACKGROUND: The effectiveness of partial posterior wrap (Toupet procedure) in
      patients with defective esophageal body motility is controversial. AIM OF THE
      STUDY: To evaluate the effect of Toupet procedure upon the outcome of
      laparoscopic (LF) and open (OF) fundoplications in gastroesophageal reflux
      disease (GERD) patients with defective esophageal body motility. PATIENTS AND
      METHODS: This study included 32 patients with severe GERD who underwent Toupet
      procedure; 18 (56.25%) OF 'and 14 (43.75%) LF. Outcome measures included
      assessment of relief of the symptoms, results of repeated endoscopy, barium
      study, manometry and pH metry; both early (within six months) and late (two years
      at least). RESULTS: Relief of heartburn was achieved in 26 patients (81.3%).
      These include 14 (77.7%) and 12 (85.7%) patients who underwent OF and LF
      respectively. Occasional dysphagia developed in six patients (18.7%) early, and
      three (9.4%) late; all were managed conservatively. Endoscopic esophagitis healed
      in 26 patients (81.3%); 14 (77.7%) OF and 12 (85.7%) LF. Mean LES and body
      pressures improved (10.5 to 17.7 and 29.0 to 41.0 mmHg respectively). Persistent
      acid reflux was detected in six patients (18.7%); two (22.3%) OF and two (14.3%)
      LF. CONCLUSION: Toupet fundoplication is an effective procedure for reflux
      control except in patients with severe GERD.

PMID- 19861850
TI  - Surgery for small bowel Crohn's disease: experience of a tertiary referral
      center.
AB  - THE AIM: The study aims to evaluate the clinical presentation and surgical
      management of small bowel Crohn's disease (CD) at a tertiary referral center in
      the Kingdom of Saudi Arabia (KSA). PATIENTS AND METHODS: A retrospective review
      of the medical records of all patients with the diagnosis of small bowel CD from
      March 1999 up to December 2003. The records of 28 patients were reviewed for
      demographic data, clinical presentation, preoperative investigations, indications
      of surgery, surgical procedures, postoperative complications and follow-up. The
      final diagnosis of CD was based on paraffin section histopathology reports.
      RESULTS: The mean age was 34 years, female to male ratio was 1:2.1. The medical
      treatment was offered to 22 patients in whom the diagnosis of CD was established
      after investigations or they were known to have CD before admission. Thirteen
      patients (46.4%) responded to medical treatment, whereas 15 patients (53.6%)
      required surgery. The indications for surgery were intestinal obstruction (seven
      patients), right iliac fossa mass lesion of uncertain nature (three patients),
      enterocutaneous fistula and pelvic collection (one patient), failure of medical
      treatment (two patients), and acute abdomen (two patients). The surgical
      procedures carried out were limited right hemicolectomy in ten patients,
      segmental bowel resection (two patients) and stricturoplasty of the stenosed
      segment (three patients). CONCLUSION: Crohn's disease is not uncommon in KSA. It
      is a disease of young patients, half of patients needed surgery at some stage.
      Intestinal obstruction remains the most common indication of surgery. The surgery
      of CD needs a good cooperation between the surgeon, radiologist and
      gastroenterologist.

PMID- 19861851
TI  - Gastric malignancy: clinicopathologic spectrum and relationship to Helicobacter
      pylori infection.
AB  - BACKGROUND: Upper gastrointestinal cancer particularly of stomach is a relatively
      frequent form of cancer. Gastric H pylori infection has been implicated in the
      pathogenesis of both gastric carcinoma and gastric lymphoma. Gastric carcinoma
      has been addressed by many articles in the Kingdom of Saudi Arabia (KSA) and the
      Middle East, while only a few addressed gastric lymphoma. AIM OF THE STUDY: To
      investigate the relative frequency of gastric carcinoma and gastric lymphoma and
      their association with H pylori infection in endoscoped patients. PATIENTS AND
      METHODS: A retrospective study of patients endoscoped at King Fahad Hospital of
      the University, Al-Khobar, KSA during the period 1983-1999 was performed.
      Endoscopy and pathology records were retrieved and reviewed. The histopathology
      slides were re-examined, applying immunohistochemical techniques on corresponding
      paraffin sections to classify the various tumors. H pylori were identified on
      routine histology and by utilizing Giemsa stain. RESULTS: During the study period
      of 17 years (1983-1999), a total of 94 endoscopically-diagnosed, histologically
      confirmed cases of gastric malignancy were identified. Of these, there were 55
      gastric adenocarcinoma and 39 gastric lymphoma. H pylori was identified in the
      adjacent gastric mucosa in 18 of all cases of gastric adenocarcinoma and in 27 of
      the 39 cases of lymphoma. CONCLUSION: The study demonstrates the comparatively
      high frequency of gastric lymphoma in this population and confirms the intimate
      association of H-pylori infection to both gastric adenocarcinoma and MALT
      lymphoma. Gastric lymphoma should always be considered in the differential
      diagnosis of gastric malignancy and the use of immunohistochemistry is essential
      for the differential diagnosis of some of these tumors.

PMID- 19861852
TI  - Crohn's disease among Saudis in Al-Gassim region.
AB  - BACKGROUND: Crohn's disease is being increasingly reported from Saudi Arabia and
      information about its pattern is still accumulating. AIM OF THE STUDY: To
      describe and classify the disease and assess the response to therapy in patients
      referred to a tertiary care centre in Gassim region, Kingdom of Saudi Arabia
      (KSA). PATIENTS AND METHODS: Fifteen Saudi patients found to have Crohn's disease
      over an eight-year period were studied. The presenting symptoms, area of
      involvement and the response to therapy were assessed. RESULTS: There were five
      males and ten females. The age of 14 patients was less than 40 years. Symptoms
      had existed for more than one year before diagnosis in 14 patients. Common
      symptoms were diarrhea, pain during defecation, blood in stool and weight loss.
      The ileum was involved in three patients, the colon in four and the involvement
      was ileocolonic in eight patients. The behavior of the disease was non
      stricturing nonpenetrating in eight, stricturing in two, penetrating in one and
      stricturing as well as penetrating in four patients. Three patients presented as
      acute appendicitis, four as intestinal obstruction and five with perianal
      disease. Histological diagnosis was possible in 12 patients. Thrombocytosis was
      present in seven patients and three had episodes of deep vein thrombosis. Eight
      patients responded to medical therapy. Surgical intervention was necessary in
      seven patients and three had multiple operations. One patient died during a
      median follow-up period of 18 months (range: 6 months to 8 years). CONCLUSION:
      Crohn's disease occurs more commonly in young Saudi females. Patients are
      symptomatic for almost a year prior to diagnosis. The presentation is variable
      and response to therapy is satisfactory. Surgery is necessary in a high number of
      patients.

PMID- 19861853
TI  - Pattern of colorectal cancer at two hospitals in the western region of Saudi
      Arabia.
AB  - PATIENTS AND METHODS: Data of all patients with CRC treated at two hospitals in
      the Western region of the Kingdom of Saudi Arabia (KSA), between 1993 and 2002,
      were collected and analyzed. RESULTS: Out of the 121 patients evaluated, ten were
      excluded because of incomplete data. Out of 111 patients, 59 (53.2%) were males,
      with a male to female ratio of 1.13: 1 and 49 (44.1 %) were Saudis. Thirty-three
      patients (29.7%) were 40 years or less and 78 (70.3%) were more than 40 years.
      Colon cancer was found in 69 patients (62.2%) and rectal cancer in 42 (37.8%).
      Stages at presentation were; stage 0 (2.7%), stage I (11.7%), stage II (23.4%),
      stage III (20.7%), stage IV (22.5%) and the staging was unknown in 18.9% of the
      patients. The most common tumor grade was moderately differentiated (38.7%),
      followed by poorly differentiated (20.7%) and well differentiated 19.8% of the
      patients. Forty-four patients (39.6%) were alive at the time of data collection,
      43 (38.7%) expired and 24 (21.6%) were lost to follow up. Correlation between age
      groups revealed that young patients had more advanced stage and poorly
      differentiated tumors than > 40 years old (p= 0.005 and 0.024 respectively).
      CONCLUSION: Compared to data from Western countries, colorectal cancer in this
      population is more common in younger patients. It presents more commonly in a
      more advanced stage and poorly differentiated type than in older patients.

PMID- 19861854
TI  - Leiomyosarcoma of the small intestine presenting as intussusception.

PMID- 19861855
TI  - Current knowledge on helicobacter pylori infection in end stage renal disease
      patients.
AB  - Gastric infection with Helicobacter Pylori in end-stage renal disease patients is
      of relevance because of its potential impact on the quality of life as well as
      morbidity and mortality of patients. Existed data on the issue are controversial,
      and we attempt in this article to evaluate the available data to approach
      extended perception of the current knowledge on the epidemiology, relevance, and
      optimum therapeutic strategies.

PMID- 19861856
TI  - Non-dialytic management of sepsis-induced acute kidney injury.
AB  - Sepsis is an important cause of morbidity and mortality. Acute Kidney Injury
      (AKI) often complicates sepsis, leading to greater complexity, higher cost of
      care and worsening prognosis. Despite the improved understanding of its
      underlying pathophysiological basis, there have been very few interventions,
      which have consistently been shown to be of value in the management of sepsis
      induced AKI. Measures such as adequate hydration, maintenance of adequate
      circulating blood volume and mean arterial pressure, and avoidance of
      nephrotoxins, are still the mainstay of prevention. Loop diuretics, mannitol and
      "low dose" dopamine have been clearly shown to be of no value in the prevention
      or treatment of AKI and may, in fact, do harm. Among the remaining
      pharmacological options, N-acetylcysteine (NAC) may have a role in the prevention
      of radiocontrast induced AKI.

PMID- 19861858
TI  - Mycophenolate sodium increases cyclosporine blood levels in renal transplant
      recipients.
AB  - Cyclosporine is an immunosuppressive agent that displays a broad intra- and inter
      individual pharmacokinetic variability. To evaluate the factors, which
      significantly influence cyclosporine blood levels in our renal transplant
      recipients, we studied 611 consecutive patients transplanted from living donors
      in Baqiyatallah hospital, Tehran, Iran from 1984 to 2005. The patients were
      divided into two groups: Group I included patients treated with mycophenolate
      sodium (MS) as an adjunctive immunosuppressive agent and Group II treated with
      azathioprine (AZA) as an adjunctive agent. Measurements of cyclosporine blood
      tough levels (C0) were performed 12 hours after the morning dose (just before the
      night dose). The mean age of the study population at time of transplantation was
      38.7 +/- 13.7 years and males formed 67% of it. Univariate analysis and
      multivariable linear regression model showed that older age at transplantation,
      treatment with MS, and time interval from time of transplantation were
      significantly related with higher C0 levels. We conclude that there is an
      interaction of immunosuppressive agents in renal transplant patients with higher
      cyclosporine levels in the recipients of MS.

PMID- 19861857
TI  - Can serial eGFR, body mass index and smoking predict renal allograft survival in
      south Asian patients.
AB  - Limited data exist regarding long-term allograft survival in South Asian patients
      in the era of modern immunosuppressive therapy. This retrospective cohort study
      was undertaken to see the graft survival based on serial eGFR, immunosuppressive
      therapy, BMI and other confounding factors including smoking in patients who have
      undergone renal transplantation in a tertiary care center in south India. Three
      hundred and three kidney transplant recipients including live and cadaveric
      transplantation performed between 2001 and 2006 were included in this study. The
      mean graft survival after transplantation was 6.38 +/- 0.11 years, graft survival
      at one, two, three and five years were 95.7%, 92.72%, 91.72% and 89.21%,
      respectively. The mean serum creatinine and eGFR in the biopsy proven acute
      rejection (BPAR) group were 1.74 +/- 0.94 mg/dL and 43.73 +/- 13.65 mL/min com
      pared with 1.24 +/- 0.59 mg/ dL and 61.50 +/- 17.40 mL/min in the non-BPAR group
      (P < 0.001 and P= 0.0159) respectively. The mean BMI in the BPAR group at one
      year was 26.59 +/- 3.18 kg/m 2 compared with 21.63 +/- 2.29 kg/m 2 in the non
      BPAR group (P < 0.05). The mean graft survival in patients who were smokers at
      the time of pretransplant evaluation was 89.3% compared with 92.5% in the non
      smokers (P=0.347). This retrospective cohort study found that serial eGFR, body
      mass index and smoking were significant predictors of graft survival following
      renal transplantation in South Asian patients.

PMID- 19861859
TI  - Impact of ethnicity, donor status and HLA matching on renal allograft survival: a
      single center study.
AB  - The role of histocompatibility testing in renal transplantation is passing
      through an immense debate on its utility in predicting long-term graft survival.
      The current study, which includes fifty-one patients with end-stage renal
      disease, aims at evaluating the impact of the HLA matching in live related donor
      (LRD) (parents, siblings and near relatives) and live unrelated donor (LURD)
      transplants on one year graft survival rates, in a single center. Patients were
      followed-up for one-year after renal transplantation and observed for renal
      complications inclu-ding infections and rejection. The incidence of acute
      rejection episodes was found to be lower in LRD transplantation complying with
      many reports published so far. HLA matching was found to be beneficial in
      obtaining better graft function and one-year graft survival rate. The current
      study found that patients from Far East of India have lower graft survival rates
      as against patients from other regions of the country. India, with its vast
      racial distribution, has a need to look into the ethnic variation and its impact
      on allograft survival.

PMID- 19861860
TI  - Evaluation of serum tumor necrosis factor alpha and its correlation with
      histology in chronic kidney disease, stable renal transplant and rejection cases.
AB  - Tumor necrosis factor alpha (TNF alpha) is a cytokine secreted by macrophages,
      helper T cells, natural killer cells, B lymphocytes and non lymphoid cells e.g.
      endothelial cells, fibroblast and tumor cell lines. Aim of the study was to find
      the utility of TNF alpha in diagnosing renal transplant rejection among the renal
      transplant cases (n=29), and comparison with the levels in patients on
      maintenance hemodialysis (n=21) and healthy controls (n=20). TNF alpha in healthy
      controls varied from 2 to 15 pg/mL. In chronic renal failure and renal transplant
      rejection cases TNF alpha was above 45 pg/mL. In stable renal transplant patients
      it was higher than normal (16 to 30 pg/mL). In both acute and chronic transplant
      rejection TNF alpha increase correlated well with histology. Thus our study
      suggests that TNF alpha level more than 45 pg/mL can be taken as an immunological
      marker of renal transplant rejection.

PMID- 19861861
TI  - Urological complications of renal transplantation: Reducing the risk.
AB  - Urological complications can have a significant effect on the outcome of renal
      transplantation including the loss of the graft. The aims of this study were to
      determine the incidence of urological complications occurring after kidney
      transplantation at our unit, and how the risk of complications can be reduced.
      All 398 renal transplantations performed at Derriford Hospital, Plymouth between
      August 1997 and December 2006 were reviewed. Twenty nine (7.3%) urological
      complications were noted with a median time to diagnosis of 8.5 days (range 1-950
      days) following transplantation; 81% occurring within two weeks. Fourteen (48.3%)
      of these patients had identifiable risk factors; 10 patients required ureteric
      reimplantation, 6 had Boari flap reconstruction, and 3 underwent transurethral
      resection prostatectomy. One graft was lost to severe ureteric necrosis. Steps to
      reduce the risk of complications include avoiding damage to organs during
      retrieval, meticulous bench preparation including hydrodilating ureters to
      exclude ureteric injury and vigilance during the transplant procedure. Prompt and
      appropriate corrective surgery can diminish the effect of urological
      complications on graft survival.

PMID- 19861863
TI  - Value of serum cystatin C as a marker of renal function in the early post kidney
      transplant period.
AB  - Management of renal transplant patients requires periodic measurement of renal
      function especially in early post transplant period. This is usually assessed by
      measuring the creatinine clearance, but because of its limitations, it is not an
      ideal marker for assessing the renal function. Serum cystatin C (sCyC) appears to
      be an endogenous marker of glomerular filtration rate (GFR). To assess the use of
      sCyC as a marker of renal function in kidney transplant patients, we compared it
      with serum creatinine (sCr) and 24-hour urine creatinine clearance (CrCl) in the
      first week post-transplantation. Among 60 patients (62.8% men, 37.2% women)
      undergoing kidney transplantation (average age: 44.87 +/- 13.37 years), we
      determined renal function at 1, 3, 5, and 7 days after kidney transplantation
      using: sCr, sCyC and CrCl in a 24-hours urine specimen. During the first 5 days
      following transplantation, there was a progressive decline in sCr levels. In the
      first 5 days, post transplantation we could not find good correlation between CrC
      and sCyC, and the sCyC increased during these 5 days, but after that in day 7,
      there was a good correlation between CrC and sCyC which is coinciding with
      decreasing the dose of steroid (r= .625). Therefore, we recommend using sCyC may
      be used as a marker of renal function after one-week post kidney transplantation.

PMID- 19861862
TI  - Reduction of the severity of ischemia reperfusion-induced pancreatitis by
      ischemic pre-conditioning of the liver.
AB  - Pre-conditioning by brief exposure to ischemia does not only protect the
      concerned organ against subsequent severe ischemic damage, but also has
      protective effect on other organs, which is called remote pre-conditioning. Our
      aim in this study was to evaluate the protective effect of brief liver ischemia
      on the pancreas against severe ischemia-reperfusion-induced pancreatitis. This
      study was performed on 30 male Wistar rats. Ischemic pre-conditioning of liver
      was performed by first clamping of the hepatic pedicle for 10 minutes. Following
      this, ischemia-reperfusion of the pancreas was performed by first clamping the
      inferior splenic artery for 30 minutes, followed by reperfusion for one hour. The
      rats were divided into three groups (10 rats in each group). Group one was the
      sham operated group, without clamping of any artery. Group two developed ischemia
      reperfusion-induced pancreatitis, without ischemic pre-conditioning of the liver,
      while Group three underwent ischemic pre-conditioning of the liver followed by
      ischemia-reperfusion of the pancreas. Ischemic pre-conditioning, applied prior to
      induction of pancreatitis, caused a reduction in plasma lipase, plasma
      interleukin-1beta and histological signs of pancreatic damage, but plasma
      interleukin-10 levels were not significantly different between the three groups.
      Ischemic pre-conditioning of the liver did not cause any alteration of the liver
      enzymes. Our study suggests that ischemic pre-conditioning of the liver reduces
      the severity of ischemia-reperfusion-induced pancreatitis. These effects are
      partly related to the reduction of pro-inflammatory interleukin -1beta.

PMID- 19861864
TI  - The effect of use of dates on serum potassium in nondiabetic hemodialysis
      patients.
AB  - Hyperkalemia is common in patients with ESRD and may contribute to mortality.
      Dates have been reported to be high in potassium content. One of the concerns on
      hemodialysis (HD) is convincing patients to give up ingestion of dates as a part
      of their diet. To determine the effect of dates on serum potassium on patients,
      we studied 9 (M: F, 6:3, mean age 47.6) non diabetic patients on chronic
      hemodialysis, without evidence of hyperkalemia on monthly labs. Nearly all the
      patients had been on dialysis for an average of four years. The average monthly
      potassium was 4.6 mmol/L. The patients ingested 100 gm of dates (Rothana and
      Sukari) on two separate dialysis sessions. Serum potassium was measured at two
      and four hours post ingestion along with ECG monitoring. The patients underwent
      their regular dialysis as scheduled. The patients acted as their own controls and
      underwent the same protocol with 20meq of KCl on a separate session. The
      potassium levels did not change significantly over the four hours with either
      variety of dates or with potassium solution. Combining the two types of dates
      resulted in a trend towards higher potassium levels than with KCl, but it did not
      reach statistical significance. We conclude that in selected HD patients without
      hyperkalemia, ingestion of a few dates does not cause significant hyperkalemia
      and could be allowed on days of dialysis prior to their dialysis sessions.

PMID- 19861865
TI  - Increasing dialysate flow rate increases dialyzer urea clearance and dialysis
      efficiency: an in vivo study.
AB  - Clearance of urea depends on the dialysis solution flow rate as well. A faster
      dialysis solution flow rate increases the efficiency of diffusion of urea from
      blood to dialysate. An in vivo study was used in order to examine the effect of
      increasing dialysate flow rate (Q D ) on dialyzer urea clearance and dialysis
      efficiency expressed as Kt/V and URR. Group assignment was at the patient level
      rather than the facility level. The study subjects consisted of 138 hemodialysis
      patients on 3-times-per-week dialysis regimens. One way ANOVA test, Student's t
      test and Logistic regression analysis were used to analyze the data.
      Statistically significant increase in Kt/V and URR was noted as the dialysate
      flow increased from 500 to 800 mL/min when a moderate efficiency dialyzer with
      large surface area (1.6 m 2 ) and high flux high efficiency dialyzers were used
      (P < 0.05). For moderate efficiency dialyzers with large surface area, Kt/V
      increased by 5.86% (P= 0.022628) and URR increased by 4.31% (P= 0.02263). Low
      efficiency and small surface area (1.2 m 2 and 1.3 m 2 ) dialyzer did not show an
      improvement in Kt/V or URR with increase in dialysate flow rate. Increasing Q D
      from 500 to 800 mL/min is associated with a statistically significant increase in
      Kt/V, URR and dialyzer clearance in moderate efficiency low flux and high
      efficiency high flux dialyzers. Hemodialysis with Q D of 800 mL/min should be
      considered in selected patients not achieving adequacy despite extended treatment
      times and optimized blood flow rates.

PMID- 19861866
TI  - Validation of predictive equations for glomerular filtration rate in the Saudi
      population.
AB  - Predictive equations provide a rapid method of assessing glomerular filtration
      rate (GFR). To compare the various predictive equations for the measurement of
      this parameter in the Saudi population, we measured GFR by the Modification of
      Diet in Renal Disease (MDRD) and Cockcroft-Gault formulas, cystatin C, reciprocal
      of cystatin C, creatinine clearance, reciprocal of creatinine, and inulin
      clearance in 32 Saudi subjects with different stages of renal disease. We
      compared GFR measured by inulin clearance and the estimated GFR by the equations.
      The study included 19 males (59.4%) and 13 (40.6%) females with a mean age of
      42.3 +/- 15.2 years and weight of 68.6 +/- 17.7 kg. The mean serum creatinine was
      199 +/- 161 micromol/L. The GFR measured by inulin clearance was 50.9 +/- 33.5
      mL/min, and the estimated by Cockcroft-Gault and by MDRD equations was 56.3 +/-
      33.3 and 52.8 +/- 32.0 mL/min, respectively. The GFR estimated by MDRD revealed
      the strongest correlation with the measured inulin clearance (r= 0.976, P=
      0.0000) followed by the GFR estimated by Cockcroft-Gault, serum cystatin C, and
      serum creatinine (r= 0.953, P= 0.0000) (r= 0.787, P= 0.0001) (r= -0.678, P=
      0.001), respectively. The reciprocal of cystatin C and serum creatinine revealed
      a correlation coefficient of 0.826 and 0.93, respectively. Cockroft-Gault formula
      overestimated the GFR by 5.40 +/- 10.3 mL/min in comparison to the MDRD formula,
      which exhibited the best correlation with inulin clearance in different genders,
      age groups, body mass index, renal transplant recipients, chronic kidney disease
      stages when compared to other GFR predictive equations.

PMID- 19861867
TI  - A study on the association between angiotensin-I converting enzyme I/D dimorphism
      and type-2 diabetes mellitus.
AB  - Type-2 diabetes mellitus (T2DM) is a chronic disorder characterized by a varying
      range of predominant insulin resistance with relative insulin deficiency, to
      predominant insulin secretory defect with or without insulin resistance. Familial
      clustering as well as epidemiological studies has shown that genetic factors play
      a role in the development and progression of the disease. Among the genetic
      factors found to be associated with development of T2DM is the angiotensin-I
      converting enzyme (ACE) gene, which is located on chromosome 17q23. This study
      was conducted to study the association between ACE gene insertion/deletion (I/D)
      polymorphism and T2DM in a Lebanese diabetic cohort. Fifty-one patients with T2DM
      and 40 control subjects from different parts of Lebanon underwent genotyping for
      the ACE I/D, which was performed by PCR using specific primers. Chi-square and
      analysis of variance (ANOVA) were used for association studies and to assess the
      differences in the values among the groups. The distribution of the genotypes in
      the patients was as follows: 15/51 (29.4%) were homozygous for deletion allele
      (DD genotype), 24/51 (47.1%) were heterozygous (ID genotype), and 12/51 (23.5%)
      were homozygous for insertion allele (II genotype). Among the control subjects,
      16/40 (40%) were homozygous for deletion (DD genotype), 13/40 (32.5%) were
      heterozygous (ID genotype), and 11/40 (27.5%) were homozygous for insertion (II
      genotype). The prevalence of the D-allele in T2DM patients (52.9%) was not
      significantly different from that in the controls (56.3%). Thus, ACE I/D
      dimorphism cannot be considered a risk factor for T2DM in the Lebanese
      population.

PMID- 19861868
TI  - Acute renal failure associated with the Rift Valley fever: a single center study.
AB  - Renal impairment is a frequent occurrence among patients with the Rift Valley
      fever (RVF), and is probably the result of hypovolemia and multiple organ
      dysfunctions in the majority of cases. This study was conducted to estimate the
      incidence of renal impairment in patients with RVF as well as to determine the
      associated mortality. Data of all patients admitted with renal impairment to the
      Gezira Hospital for Renal Diseases, Sudan, during the epidemic of RVF between
      September 2007 and January 2008 were analyzed. The total number of patients with
      RVF was 392 of whom, 194 were admitted to the Medani Teaching Hospital. Renal
      impairment was detected in 60% of the admitted patients; 90% of them needed
      dialysis treatment. The mortality rate was 31% in patients with acute renal
      failure, 25% in those with the hepatorenal syndrome and 31% in patients with
      primary hepatic involvement and mild renal impairment. The overall mortality was
      40%. Our study suggests that RVF remains a major cause of acute renal failure
      with considerable mortality, although progression to chronic renal failure was
      not seen. Early renal substitution therapy fosters the best hope for survival.

PMID- 19861869
TI  - Dissecting aortic aneurysm in maintenance hemodialysis patients.
AB  - The dissecting aortic aneurysm (DAA) is a rare pathology that may result in fatal
      outcome. We report follow up of three cases of DAA patients undergoing
      maintenance hemo-dialysis who were managed conservatively.

PMID- 19861870
TI  - Hydatid cyst disease in a renal allograft recipient.

PMID- 19861871
TI  - Supraventricular tachycardia following insertion of a central venous catheter.
AB  - Placement of central venous catheters (CVCs) in patients is associated with
      several risks including endocardial injury and dysrhythmias. In addition, CVC
      extending into intracardiac chambers can provoke premature atrial and ventricular
      complexes, which have been reported to initiate supraventricular tachycardia
      (SVT). A 15-year-old boy with end-stage renal failure developed SVT after
      insertion of a CVC.

PMID- 19861872
TI  - Use of sodium thiosulfate in the treatment of calciphylaxis.
AB  - Calciphylaxis is an infrequent but severe entity found in chronic dialysis
      patients. Its clinical pattern consists of tissue ischemia with itchy and painful
      subcutaneous nodules and plaques, most often located on the abdomen, buttocks,
      thighs and/or legs. These injuries evolve to extensive superficial necrosis of
      the skin overlying the panniculitis, with ulceration, overinfection and
      consequent sepsis. Current treatment modalities used to counteract this pathology
      are not entirely effective. A new treatment reported for calciphylaxis, is the
      use of intravenous sodium thiosulfate. This inorganic salt is already used in the
      treatment of intoxication caused by cyanide, in patients with calcific
      nephrolithiasis and tumoral calcinosis, with very good and safe results. We
      herewith report a case of calciphylaxis that was cured using intravenous sodium
      thiosulphate treatment.

PMID- 19861873
TI  - A huge renal capsular leiomyoma mimicking retroperitoneal sarcoma.
AB  - A huge left renal capsular leiomyoma mimicking retroperitoneal sarcoma presented
      in a patient as an abdominal mass. Computed tomography displayed a large
      heterogeneous retro-peritoneal mass in the left side of the abdomen with inferior
      and medial displacement as well as loss of fat plane with the left kidney.
      Surgical exploration revealed a capsulated mass that was tightly adherent to the
      left kidney; therefore, total tumor resection with radical left nephrectomy was
      performed. Histopathology ultimately confirmed the benign nature of the mass.
      This is the largest leiomyoma reported in literature to the best of our
      knowledge.

PMID- 19861874
TI  - Drug-induced interstitial nephritis in a child with idiopathic nephrotic
      syndrome.
AB  - Acute renal failure (ARF) is a rare but severe complication of active idiopathic
      nephrotic syndrome (INS) in children. It may be due to several causes with
      different outcomes. Both the clinical picture of the patient as well as
      laboratory, imaging and histopathological findings may help in the diagnosis. We
      present a case of drug-induced acute interstitial nephritis (AIN), complicated
      with ARF, in a 2(1/2) -year-old girl with active INS. The child was referred to
      the Hippokration General Hospital, Thessaloniki, Greece hospital with steroid
      resistant NS; renal biopsy was performed, which did not show any remarkable
      findings and cyclosporine was administered in addition to steroid therapy. The
      first day after biopsy, the child developed gross hematuria and abdominal pain
      and an antibiotic was added to her treatment. In the following days, fever,
      vomiting, hypertension and ARF occurred. Ultrasound study revealed enlarged
      kidneys with increased echogenity and loss of corticomedullary differentiation.
      The antibiotic and cyclosporine were stopped and the child was managed with
      furosemide, nifedipine and steroids. A second renal biopsy was performed, which
      confirmed the diagnosis of acute interstitial nephritis. The child did not
      require dialysis therapy. Her urine output improved gradually and the serum
      creatinine normalized one month after the initial episode. Our case re-emphasizes
      the need for investigation of factors precipitating ARF in children with
      idiopathic NS.

PMID- 19861875
TI  - Epstein syndrome with rapid progression to end stage renal disease.
AB  - The association of haematological abnormalities and hereditary nephritis is rare;
      it is mainly included in a spectrum of autosomal dominant macrothrombocytopenias:
      May-Hegglin anomaly, Fechtner, Sebastian, Epstein and Alport syndrome with macro
      thrombocytopenia. We are presenting a missed case of a boy who presented with
      epistaxis and his diagnostic work up revealed macrothrombocytopenia,
      sensorineural hearing loss and chronic nephropathy which constitute the Epstein
      syndrome, with rapid deterioration of kidney function.

PMID- 19861876
TI  - Acute interstital nephritis associated with rifampicin therapy.

PMID- 19861877
TI  - Concomitant presence of renal cell carcinoma and adenocarcinoma of the colon.

PMID- 19861878
TI  - Calcific uremic arteriopathy.

PMID- 19861879
TI  - Rituximab to treat active SLE in a hemodialysis patient.

PMID- 19861880
TI  - Alport's syndrome.

PMID- 19861881
TI  - Survey of attitude of physicians on updates in the management of anemia in
      chronic kidney disease patients - an eye-opener.

PMID- 19861882
TI  - Catheter related infection in hemodialysis patients.
AB  - To determine the frequency of hemodialysis (HD) catheter related infection,
      causative microorganisms and predisposing factors contributing to these
      infections at our center, we conducted a prospective study in 2007 involving 57
      (45.6% males) patients in whom a temporary catheter was inserted for HD. The
      patients were followed for one month to document any episodes of hemodialysis
      catheter related infection (HCRI). There were 11 (19.3%) patients who developed
      HCRI proven by blood culture; 5 patients were infected with more than one
      organism. Staphylococcus Coagulase negative and Staphylococcus aureus (S. aureus)
      remain the most common pathogens. All the organisms were sensitive to antibiotics
      administered empirically, however, 3 patients developed multiple resistant S.
      aureus (MRSA). All the infected patients experienced previous episodes of HCRI,
      which formed a risk factor in addition to low albumin when compared to the non
      infected group (P=0.024 and P= 0.001, respectively). We conclude that the rate of
      HCRI and the causative organisms found in our study is comparable to previous
      reports. We still need to adopt measures to minimize the use of temporary
      vascular accesses by creation of fistulas in a timely fashion.

PMID- 19861883
TI  - Urolithiasis in Tunisian children: a study of 100 cases.
AB  - The aim of this study is to assess the clinical and biological characteristics of
      renal stone disease among children living in the coastal region of Tunisia. This
      retrospective multi-center study included 100 children under the age of 16 years,
      who presented with urinary stones. The patients' charts were reviewed with regard
      to age at diagnosis, sex, history and physical examination as well as laboratory
      and radiologic findings. Stone analysis was performed by infrared
      spectrophotometry. The male/female sex ratio was 1.5 to 1. The clinical
      presentation of this pathology was dominated by dysuria. Stones were located in
      the upper urinary tract in 76 cases (76%). A total of 13% of the study subjects
      had positive urine cultures. Metabolic investigations were performed in all
      patients and were normal in 80 cases. Whewellite (calcium oxalate) was found in
      77 stones (77.0%). Stone section was made of whewellite in 69.0% of cases and
      ammonium urate in 47.0%. Struvite stones were more frequently seen in the lower
      urinary tract. Our study suggests that the epidemiological profile of renal
      stones in Tunisia has changed towards a predominance of calcium oxalate stones
      and upper tract location. Also, the male predominance of pediatric urolithiasis
      is becoming less obvious in Tunisia.

PMID- 19861884
TI  - Is short term outcome of Iranian renal transplant recipients affected by mean
      first 6 months C2 level?
AB  - International Consensus Conference (ICC) has suggested that the whole blood level
      of Cyclosporine (CsA) be kept strictly at a certain level. However, it is not
      well understood whether failing to maintain these levels will affect the short
      term outcome in different patient populations or not. We aimed to assess if the
      short term outcome of Iranian renal transplant recipients will be affected by
      first 6 months C2 level. In a retrospective cohort, 265 consecutive kidney
      transplant recipients were categorized as group with mean C2 lower than
      recommended range (mean C2 levels in the first 6 month after transplantation
      lower than the recommended ranges; n=213) and group with mean C2 within
      recommended range (mean C2 levels in the first 6 month after transplantation
      within the recommended range; n=52). All recipients were negative for panel
      reactive antibody, and had received their first (living unrelated) kidney
      transplantation in Baqiyatallah hospital, between 2002 and 2003. The groups were
      similar in characteristics and 6 months, 1, 2, and 3 years patient and graft
      survival rates were considered as outcome. No significant difference was observed
      in patient and graft survival rates between the two groups (P > 0.05). The
      patient survival rate in group with mean C2 lower than recommended range and
      group with mean C2 within recommended range were: 6 months: 98% vs. 98, 1 year:
      97% vs. 98%, 2 years: 97% vs. 98% and 3 years: 97% vs. 98%. The graft survival
      rate in the above groups were as follows: 6 months: 93% vs. 91%, 1 year: 92% vs.
      91%, 2 years: 92% vs. 77% and 3 years: 89% vs. 69%, respectively. The result of
      our study showed that lower mean C2 levels was not necessarily accompanied with a
      worse short term outcome in our patients. This finding suggests that the optimal
      level of C2 may be different in ethnic populations.

PMID- 19861885
TI  - Biochemical nutritional parameters and their impact on hemodialysis efficiency.
AB  - To determine the nutritional status of chronic hemodialysis (HD) patients and the
      association of changes in serum albumin levels, C-reactive protein (CRP), low
      density lipoprotein (LDL) cholesterol and body mass index (BMI) as indicators of
      nutritional status with the urea reduction ratio (URR) during dialysis, we
      studied 201 chronic HD patients (97 males and the mean age was 51 +/- 15 years).
      Diabetes was the cause of chronic kidney disease (CKD) in 34% of the patients,
      hypertension in 57%, chronic glomerulonephritis in 12%, and obstructive uropathy
      in 10%. BMI less than 18.5 (under weight) was found in 17% of patients, more 18.5
      but less than 25 (normal) in 56%, more than 25 but less than 30 (overweight) in
      21%, and more than 30 (obese) in 6%. The laboratory investigations revealed
      hypercalcemia in 62% of the patients (15 patients were found to have tertiary
      hyperparathyroidism), total cholesterol less than 100 mg/dL in 6% (mean 152 +/-
      37.5 mg/dL), and URR of less than 60% in 12% of patients and greater than 60 but
      less than 65% in 33%. Hypoalbuminemia was associated with poor URR (P < 0.05),
      whereas no statistically significant correlation was found between URR and iPTH,
      LDL cholesterol, CRP and body mass index. We conclude that poor nutritional
      status was detected among a significant number of our patients with poor dietary
      education. Increased risk of malnutrition was significantly associated with older
      age and inadequate dialysis dose. Hypoalbuminemia was the single most important
      factor associated with poor URR.

PMID- 19861886
TI  - The effect of ligation of the distal vein in snuff-box arteriovenous fistula.
AB  - Arterio-venous fistula (AVF) in the snuff-box region is one of the current
      techniques used for creating a vascular access in patients undergoing dialysis.
      The aim of this study is to find out whether ligating the distal vein in AVF in
      the snuff-box will bring about any change in the efficiency and complications of
      the fistula. Sixty patients (30 males, 30 females) suffering from chronic renal
      failure, who had been admitted for creating an AVF, were randomly divided into
      two groups after having filled out consent forms. After the AVF was made, the
      distal vein was ligated in the first group, but not in the second group. The
      patients were discharged after being given the necessary advice on how to take
      care of their fistula. They were examined on post-surgical days 1, 30 and 90.
      Early efficiency in the ligated and non-ligated groups was 100% and 96.7%
      respectively while late efficiency in the two groups was 90% and 83.4%,
      respectively (P > 0.05). The most common complication in both groups was
      thrombosis (11.7%). Venous hypertension and edema were observed in two patients
      (both from the non-ligated group) and infection of the surgical site was observed
      in only one patient. Our study suggests that, considering the high efficiency
      level and low complication rate, AVF at the snuff-box region constitutes one of
      the best possible vascular accesses for patients undergoing hemodialysis.
      Ligation of the distal vein prevents the development of venous hypertension in
      the fistula.

PMID- 19861887
TI  - The vanguard sperm cohort of the boar ejaculate is overrepresented in the tubal
      sperm reservoir in vivo.
AB  - In boars, sperm cohorts are sequentially emitted in epididymal cauda fluid and
      resuspended in different mixtures of accessory sex gland secretions while
      ejaculated in various fractions. During natural mating, these ejaculate fractions
      sequentially enter the cervix-uterine lumen, are quickly transported towards the
      tips of the uterine horns and colonize the oviductal sperm reservoirs (SR). Using
      a simple experiment, we tested the hypothesis that the first ejaculated sperm
      subpopulation (fortuitously present in the peak portion of the sperm-rich
      fraction [SRF], the so-called Portion 1, P1) is, by reaching first the SR,
      overrepresented there. Spermatozoa from P1- and of P2- (last portion of the SRF
      and the Post-SRF) were collected from 3 fertile boars. P1-spermatozoa were
      fluorophore DNA-stained, while P2-spermatozoa were kept unstained. Weaned estrous
      sows were conventionally inseminated (12 h after onset of estrus) with similar
      sperm numbers (approx 10 x 10(9) spermatozoa) per portion but in different orders
      as follows: (i) a mix of P1 and P2 aliquots (control, P1+P2, n=5), or testing
      (ii) a sequential order (P1-P2, Treatment A, n=5) or (iii) an inverse order (P2
      P1, Treatment B, n=5) of cohort AI. Sows were euthanized approx 3 h post-AI, and
      the SRs were flushed to recover the spermatozoa, which were accounted for as
      stained or unstained. The total number of spermatozoa flushed did not differ
      between groups or boars (NS, ranging 0.9 to 2.0 x 10(9)). Sequential, in vivo
      like, sperm deposition (P1-P2, Treatment A) yielded the highest proportion of
      stained P1-spermatozoa in the SRs (59.8 +/- 5.66%, means +/- SEM) compared with
      when the order was reversed (P2-P1, Treatment B; 15.6 +/- 2.1% P1-spermatozoa,
      P<0.05) or P1 and P2 sperm suspensions were mixed (control, 36.9 +/- 2.70% P1
      spermatozoa, P<0.05). The tested hypothesis proved valid; if inseminated in the
      same order as ejaculated in vivo, P1-spermatozoa become overrepresented in the
      SR. The physiological consequences of this skewed SR-colonization are discussed
      in this paper alongside the advantageous use of P1-spermatozoa for handling,
      including cryopreservation.

PMID- 19861888
TI  - Cerebral metabolism in dogs assessed by (18)F-FDG PET: a pilot study to
      understand physiological changes in behavioral disorders in dogs.
AB  - The positron emission tomography (PET) imaging technique, which is utilized in
      human behavior and psychiatric disorder research, was performed on the brains of
      clinically normal mixed breed dogs, 3 hound-type (long floppy ears) mixed breed
      dogs and 3 non-hound retriever-type mixed breed dogs. Glucose metabolism was
      obtained with F-18 fluorodeoxyglucose (FDG), and quantitative analysis was
      performed by standardized uptake value (SUV) measurement. Magnetic resonance (MR)
      images were obtained in each dog, and these images were superimposed on PET
      images to identify anatomical locations. The glucose metabolism in each region of
      interest was compared between the three hound-type dogs and 3 non-hound-type
      dogs. The two anatomically different types of dog were compared to assess whether
      breed-typical behavioral tendencies (e.g., sniffing behavior in hound-type dogs,
      staring and retrieving in Labrador-type dogs) are reflected in baseline brain
      metabolic activity. There were no significant differences between the hound-type
      dogs and non-hound-type dogs in cerebral SUV values. These data might serve as
      normal canine cerebral metabolism data for FDG PET studies in dogs and form the
      basis for investigations into behavioral disorders in dogs such as compulsive
      disorder, anxiety disorders and cognitive dysfunction.

PMID- 19861889
TI  - The polysynaptic pathways from the low threshold cutaneous afferents of the trunk
      to motoneurons innervating hindlimb muscles in the spinal cat.
AB  - We studied the reflex actions of the cutaneous afferents innervating the trunk to
      hindlimb motoneurons in the spinal cat using an intracellular recording
      technique. Stimulation of the trunk cutaneous afferents entering into the L2-L5
      spinal segment produced different types of polysynaptic potentials in hindlimb
      motoneurons via polysynaptic neuronal pathways. The trunk cutaneous afferents
      predominantly caused excitatory PSPs in the flexor motoneurons and inhibitory
      PSPs in the extensor motoneurons. The size and latency of polysynaptic potentials
      were related to the proximity of the spinal segments of the nerves stimulated to
      the spinal segments of motoneurons. These findings suggest that the neuronal
      pathways from trunk cutaneous afferents to hindlimb motoneurons play an important
      role in coordinating between the trunk and hindlimbs.

PMID- 19861890
TI  - Long-term Mechanical Circulatory Support System reliability recommendation by the
      National Clinical Trial Initiative subcommittee.
AB  - The Long-Term Mechanical Circulatory Support (MCS) System Reliability
      Recommendation was published in the American Society for Artificial Internal
      Organs (ASAIO) Journal and the Annals of Thoracic Surgery in 1998. At that time,
      it was stated that the document would be periodically reviewed to assess its
      timeliness and appropriateness within 5 years. Given the wealth of clinical
      experience in MCS systems, a new recommendation has been drafted by consensus of
      a group of representatives from the medical community, academia, industry, and
      government. The new recommendation describes a reliability test methodology and
      provides detailed reliability recommendations. In addition, the new
      recommendation provides additional information and clinical data in appendices
      that are intended to assist the reliability test engineer in the development of a
      reliability test that is expected to give improved predictions of clinical
      reliability compared with past test methods. The appendices are available for
      download at the ASAIO journal web site at www.asaiojournal.com.

PMID- 19861891
TI  - Validation of putative reference genes for normalization of Q-RT-PCR data from
      paraffin-embedded lymphoid tissue.
AB  - Normalization of quantitative reverse transcription-PCR (Q-RT-PCR) data to
      appropriate tissue-specific reference genes is an essential part of interpreting
      the results. This study aimed to determine the most appropriate reference genes
      for normalizing gene expressions in lymphatic tissue, represented by non
      neoplastic lymph nodes and diffuse large B-cell lymphomas, by using 2 statistical
      software applications, geNorm and NormFinder. In addition, we wanted to validate
      the usefulness of paraffin-embedded samples for Q-RT-PCR studies by investigating
      gene expressions of relevant target genes in paired frozen and paraffin-embedded
      samples. Moreover, we studied the impact of amplicon sizes on the efficiency of Q
      RT-PCR in paraffin-embedded tissues. Six putative reference genes were tested for
      stability of expression in 21 pairs of snap-frozen and formalin-fixed, paraffin
      embedded lymph nodes and lymphomas. The genes were ranked according to their
      suitability as reference genes. According to both statistical approaches, beta
      glucoronidase was the single most appropriate reference gene in both snap-frozen
      and paraffin-embedded samples. TATA box-binding protein gene and Abelson murine
      leukemia viral oncogene homolog 1 gene were also highly ranked by both programs.
      In addition, we measured the relative expressions of 7 target genes by Q-RT-PCR,
      using PCR primer-probes with amplicon sizes up to 105 bases. The correlation
      coefficient for expression measured in matched frozen and paraffin-embedded
      samples was 0.93 (P<0.01) after normalization with the appropriate reference
      genes. Thus, we show that formalin-fixed, paraffin-embedded lymphoid samples are
      suitable for Q-RT-PCR when using thoroughly validated reference genes.

PMID- 19861892
TI  - In situ detection of aspergillus 18s ribosomal RNA Sequences using a terminally
      biotinylated locked nucleic acid (LNA) probe.
AB  - Locked nucleic acids (LNA) are modified nucleotides where a ribonucleoside is
      linked between the 2'-oxygen and the 4'-carbon atoms with a methylene unit. LNA
      oligonucleotides exhibit increased thermal stability toward complementary DNA and
      RNA with characteristically higher melting temperatures. In situ hybridization
      (ISH) using LNA oligonucleotide probes targeting fungal ribosomal RNA (rRNA)
      sequences has not been described. This study details an ISH procedure by using a
      biotin-labeled LNA probe targeting Aspergillus spp.18s rRNA sequences. A genus
      specific 3' terminally biotin-labeled oligonucleotide probe was commercially
      synthesized by using a mixture of DNA (60%) and LNA (40%). A rapid, 2-hour,
      nonisotopic ISH procedure was developed and performed on 20 culturally proven
      formalin-fixed, paraffin-embedded (FFPE) cases of Aspergillus spp. By ISH, the
      LNA probe effectively detected Aspergillus spp. rRNA sequences in all specimens.
      Compared with a DNA probe with the same sequence, the LNA probe produced a
      stronger signal. ISH with the Aspergillus-specific LNA probe was negative on
      culture-proven cases of other fungal pathogens including Zygomyces and Fusarium.
      ISH with an LNA oligonucleotide probe targeting Aspergillus 18s rRNA sequences is
      useful for rapidly detecting Aspergillus spp. in paraffin-embedded tissue
      specimens. This test could be used when fungal pathogens are observed in tissue
      but cultures are negative or have not been performed. ISH with LNA probes may be
      useful for detecting a variety of fungal pathogens in formalin-fixed, paraffin
      embedded tissue specimens.

PMID- 19861893
TI  - Real-time quantitative assay for routine testing of HCV RNA in formalin-fixed,
      paraffin-embedded liver samples.
AB  - The assessment of hepatitis C virus (HCV) RNA in liver tissues is clinically
      relevant in cases where histology, liver function tests, and HCV serology are not
      sufficient for a definitive diagnosis of HCV-related hepatitis. We analyzed 215
      formalin-fixed, paraffin-embedded liver needle biopsies from patients infected
      with HCV genotypes 1b and 2. HCV RNA extracted from paraffin sections were
      quantified by means of a TaqMan real-time reverse transcription-polymerase chain
      reaction method. The quantification of HCV RNA in liver tissue was correlated
      with the amount of HCV detected by immunohistochemistry (IHC) on paired frozen
      biopsies, the HCV RNA load in the serum, and the main serum tests of liver
      function and cholestasis. HCV RNA was detected by real-time reverse transcription
      polymerase chain reaction in 169 liver biopsies (78.6%) with a mean value of
      13.59+/-37.25 IU/ng. Tissue HCV RNA levels strongly correlated with the IHC
      results (P<0.001, Spearman test), HCV serum load (P<0.001), aspartate
      aminotransferase (P=0.001), gamma-glutamyl transpeptidase (P=0.012), and
      aspartate aminotransferase/alanine aminotransferase ratio (P=0.029). HCV RNA was
      amplified in up to 7-year-old archival tissue samples. Real-time HCV RNA
      quantification on archival liver tissue may be clinically relevant in case of
      "occult" HCV infection or for the diagnosis of patients with known HCV infection
      and hepatic dysfunction but seronegative for HCV RNA. The assessment of the
      levels of HCV RNA in the liver might also be important for monitoring the
      effectiveness of antiviral therapy and the progression of disease in patients
      with chronic HCV hepatitis.

PMID- 19861894
TI  - UGT1A1 promoter genotype is not strongly associated with severity of coronary
      artery disease.
AB  - Atherosclerosis is a leading cause of morbidity and mortality. Oxidative stress
      is thought to play a role in its pathogenesis. Bilirubin is an endogenous
      antioxidant that is mildly elevated in people with Gilbert syndrome. Homozygosity
      for a A(TA)7TAA variant of the UDP-glucuronosyltransferase 1 family, polypeptide
      A1 (UGT1A1) promoter is necessary for expression of the Gilbert phenotype. We
      studied the relationship between coronary artery disease (CAD) and the Gilbert
      genotype. Decedents who underwent autopsy were categorized into none/mild,
      moderate, and severe CAD groups based on autopsy findings. Known CAD risk factors
      were evaluated for each decedent in the severe CAD group (n=35), and for an age,
      race, and sex-matched control group with none/mild CAD (n=45). Formalin-fixed
      paraffin-embedded (FFPE) tissue was tested for UGT1A1 promoter variants by
      polymerase chain reaction and capillary electrophoresis. To our knowledge, this
      is the first study to successfully apply UGT1A1 promoter genotyping to formalin
      fixed paraffin-embedded tissue, which may facilitate more thorough examination of
      clinicopathologic correlations. The frequency of the Gilbert genotype was
      compared between the none/mild cohort and the severe cohort. UGT1A1 promoter
      genotype data were obtained for 76/80 cases. The overall frequency of the Gilbert
      genotype compared well with previously reported frequencies at 16%, with a
      frequency of 16% in the none/mild CAD group and 15% in the severe CAD group.
      These findings suggest that UGT1A1 promoter genotype is not a major factor
      contributing to risk of CAD.

PMID- 19861895
TI  - Chromosome 18q deletion as a novel molecular predictor for colorectal cancer with
      simultaneous hepatic metastasis.
AB  - Currently, surgical treatment for colorectal hepatic metastasis is performed with
      low mortality and morbidity rates. However, there is no definitive marker that
      predicts patient outcome. The aim of this study is to identify the molecular
      predictor of survival along with its clinical properties. Fifty-six patients were
      surgically treated for colorectal cancer and synchronous hepatic metastasis from
      January 1994 to December 2004. Clinicopathologic and molecular factors were
      reviewed in association with overall survival (OS) and disease-free survival
      (DFS). Chromosome 18q deletion in the primary tumor was a molecular predictor
      that affected OS (P=0.021). Decreased expression of the Smad4 protein tended to
      affect the outcome; however, no statistical significance was observed (P=0.29:OS,
      P=0.45:DFS). Preoperative carcinoembryonic antigen (P=0.013) and carbohydrate
      antigen 19-9 (CA19-9) (P<0.0001) levels were poor clinical predictors of OS. The
      number of primary lymph nodes was the only pathologic factor that affected DFS
      (P=0.0052). The number and diameter of hepatic metastasis had no influence on
      survival. In conclusion, we demonstrated that chromosome 18q deletion, in
      conjunction with high carcinoembryonic antigen and CA19-9 levels, is an
      unfavorable prognostic factor. This novel molecular predictor is helpful in
      identifying patients who would benefit from surgical resection.

PMID- 19861896
TI  - Automated brain tumor biopsy prediction using single-labeling cDNA microarrays
      based gene expression profiling.
AB  - AIMS: Gene signatures obtained from microarray experiments may be of use to
      improve the prediction of brain tumor diagnosis. Nevertheless, automated and
      objective prediction with accuracy comparable to or better than the gold standard
      should be convincingly demonstrated for possible clinician uptake of the new
      methodology. Herewith, we demonstrate that primary brain tumor types can be
      discriminated using microarray data in an automated and objective way. METHODS:
      Postsurgical biopsies from 35 patients [17 glioblastoma multiforme (Gbm) and 18
      meningothelial meningioma (Mm)] were stored in liquid nitrogen, total RNA was
      extracted, and cDNA was labeled with Cy3 fluorochrome and hybridized onto a cDNA
      based microarray containing 11,500 cDNA clones representing 9300 loci. Scanned
      data were preprocessed, normalized, and used for predictor development. The
      predictive functions were fitted to a subset of samples and their performance
      evaluated with an independent subset. Expression results were validated by means
      of real time-polymerase chain reaction. RESULTS: Some gene expression-based
      predictors achieved 100% accuracy both in training resampling validation and
      independent testing. One of them, composed of GFAP, PTPRZ1, GPM6B and PRELP,
      produced a 100% prediction accuracy for both training and independent test
      datasets. Furthermore, the gene signatures obtained, increased cell
      detoxification, motility and intracellular transport in Gbm, and increased cell
      adhesion and cytochrome-family genes in Mm, agree well with the expected biologic
      and pathologic characteristics of the studied tumors. CONCLUSIONS: The ability of
      gene signatures to automate prediction of brain tumors through a fully objective
      approach has been demonstrated. A comparison of gene expression profiles between
      Gbm and Mm may provide additional clues about patterns associated with each tumor
      type.

PMID- 19861897
TI  - PIK3CA in breast carcinoma: a mutational analysis of sporadic and hereditary
      cases.
AB  - The PI3K-Akt cascade is a key signaling pathway involved in cell proliferation,
      survival, and growth. Activating PIK3CA mutations have been reported in breast
      carcinoma (BC). The aim of this study was to characterize the PIK3CA mutations at
      exons 9 and 20 in a series of 176 sporadic and 22 hereditary BCs and to correlate
      the results with clinicopathologic parameters and survival. In sporadic BC, 68
      missense mutations were detected. PIK3CA mutations were significantly associated
      with ER+ in HER2-negative cases. A higher frequency of PIK3CA mutations was
      present in lobular carcinoma compared with ductal carcinoma (50% vs. 35%). There
      was no association between the survival and PIK3CA mutational status. In
      hereditary BC, PIK3CA mutations were found only in the BRCA2 group. The PIK3CA
      mutation seems to characterize the luminal-type BC, in both sporadic and BRCA2
      mutated forms, and is absent in the basal-type BC, in both the sporadic and BRCA1
      mutated forms.

PMID- 19861899
TI  - Urgent need for coordination in adopting standardized antiretroviral adherence
      performance indicators.

PMID- 19861898
TI  - Molecular diagnosis of Ewing sarcoma family of tumors: a comparative analysis of
      560 cases with FISH and RT-PCR.
AB  - AIMS: To compare the sensitivity and specificity of fluorescence in situ
      hybridization (FISH) with reverse transcription polymerase chain reaction (RT
      PCR) in the diagnosis of Ewing sarcoma family of tumors (ESFTs) and other small
      round-cell tumors (SRCTs) in formalin-fixed paraffin-embedded tissue assembled in
      tissue microarrays (TMAs). The second objective is to confirm the value of
      molecular methods and immunohistochemical (IHC) assays, to perform a differential
      diagnosis between ESFTs and SRCTs with similar or overlapping morphology.
      MATERIALS AND METHODS: A total of 560 cases were selected for the present study
      out the 806 cases collected from the PROgnosis and THerapeutic Targets in the
      Ewing's Family of TumorS project. Case selection bias included only the cases
      with enough material to enable the TMA construction, as FISH analysis and the
      majority of IHC studies were performed in TMAs. Histopathologic, IHC, and
      molecular assays were carried out. RESULTS: Of the 560 total cases, 411 (73.4%)
      were considered informative (with results by FISH and/or RT-PCR assays). From the
      informative cases, 382 (92.9%) were diagnosed as ESFT, 23 cases (5.6%) as non
      ESFT but with specific diagnosis for another established entity, and 6 cases
      (1.5%) as small round cell tumors not otherwise specified. Sensitivity and
      specificity for the FISH assays was 96.3% and 95.2%, respectively, whereas RT-PCR
      presented a sensitivity of 97.5% and specificity of 92.9%. In concordant cases,
      both methods showed a sensitivity and specificity of 99.2% and 100%,
      respectively. Twenty-nine cases (7.1%) initially interpreted at morphologic level
      as atypical ESFTs were finally reclassified, with the support of molecular
      methods and IHC, as either non-ESFT with another specific histologic type or as
      small round cell tumors not otherwise specified. CONCLUSIONS: FISH and RT-PCR are
      ancillary techniques possessing high sensitivity in the diagnosis of ESFT;
      nevertheless, FISH is more specific than RT-PCR in the diagnosis of formalin
      fixed paraffin-embedded tissue. Both methods in combination displayed the highest
      sensitivity and specificity. The combination of histopathologic, IHC, and
      molecular findings is the method of choice for the diagnosis of ESFT, as well as
      for the differential diagnosis with other SRCTs.

PMID- 19861900
TI  - Interactions with parents and friends among chronically ill children: examining
      social networks.
AB  - OBJECTIVE: Children with medical conditions often experience a combination of
      positive and negative social interactions with parents and friends. Adult
      research examining cross-domain buffering effects has documented that supportive
      social ties can make up for shortcomings in other social relationships. This
      study examined whether negative effects of strained relationships with loved ones
      can be buffered when children feel supported by individuals in different support
      networks (i.e., cross-domain buffering effects). METHOD: Children with Type I
      diabetes (n = 56), chronic asthma (n = 54), and cystic fibrosis (n = 17)
      completed questionnaires during an outpatient hospital visit that assessed
      perceptions of support and strain from parents and friends, quality of life, self
      concept, and emotional/behavioral difficulties. Parental strain was
      conceptualized as parental overprotection and parental rejection. RESULTS:
      Hierarchical regression analyses showed that friend support buffered the adverse
      effects of parental strain on child quality of life, self-concept, and
      emotional/behavioral difficulties. Interestingly, parental support did not buffer
      the negative effects of experiencing strained relationships with friends; only
      main effects on outcome were found. These findings partially support our
      hypotheses of cross-domain buffering. CONCLUSIONS: In this study, friendships
      were a protective factor for children who experienced strained relationships with
      parents. In contrast, although parent support had a direct impact on child
      outcome, it did not make up for feeling rejected by friends. Because close
      relationships are often strained during medical stressors, findings underscore
      the importance of promoting social connectedness in chronically ill children to
      maximize opportunities for experiencing positive social relationships.

PMID- 19861901
TI  - Delays in lung cancer care: time to improve.

PMID- 19861902
TI  - Fluorodeoxyglucose uptake predicts survival in a CT screening trial.

PMID- 19861903
TI  - Peripheral direct adjacent lobe invasion non-small cell lung cancer has a similar
      survival to that of parietal pleural invasion T3 disease.
AB  - INTRODUCTION: The postoperative prognosis of peripheral adjacent lobe invasion
      non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to
      determine the postoperative prognosis of NSCLC with direct adjacent lobe invasion
      by comparing it with that of visceral pleural invasion (primary lobe) T2 disease,
      and parietal pleural invasion T3 disease, and hence determine its most
      appropriate T category. METHODS: A retrospective analysis was conducted to assess
      the survival of patients with peripheral direct adjacent lobe invasion NSCLC
      (group A), and it was compared with that of patients with visceral pleural
      invasion of the primary lobe (group B) and parietal pleural invasion (group C).
      All patients were node-negative on pathologic examination. Kaplan-Meier method
      was used to compare the postoperative survival between groups. RESULTS: A total
      of 263 patients were analyzed. The overall survival rates in groups A (n = 28), B
      (n = 167), and C (n = 68) at 5 years were 40.7, 54.6, and 41.9%, respectively;
      corresponding median survival in three groups were 53, 71, and 40 months,
      respectively. The survival difference among three groups was statistically
      significant (p = 0.031). A similar survival was observed between groups A and C,
      whereas group B had a much better survival than other groups. CONCLUSIONS:
      Peripheral adjacent lobe invasion NSCLC has a similar survival prognosis with
      that of parietal pleural invasion T3 disease and hence should be classified as T3
      rather than T2. However, further studies are warranted.

PMID- 19861904
TI  - Five-year outcome of lung cancer detection in patients with and without airflow
      obstruction in a primary care outpatient practice.
AB  - INTRODUCTION: We have previously published the outcome of a community-based lung
      cancer screening program. We now report on the 5-year follow-up of this study and
      include both patients with and without airflow obstruction. MATERIALS AND
      METHODS: One thousand two hundred fifty-six patients completed questionnaires in
      the office of their primary care physicians, and 430 of this group were assessed
      to be at high risk for lung cancer. These patients then underwent spirometry, and
      88 of 126 patients with airflow obstruction consented to lung cancer screening
      test. TESTING METHODS: Complete screening testing included spirometry, two-view
      chest radiograph, chest CT scan, and sputum cytology examinations. RESULTS: Eight
      lung cancers were found in the high-risk group with airflow obstruction. No more
      cancers were found in the tested group in the 5 years since the earlier report.
      Ten cancers were found in the 304 patients with normal airflow, not previously
      reported. In all, 18 lung cancers were found in 430 patients deemed at risk by a
      simple one-page questionnaire (4.2%). CONCLUSIONS: A questionnaire, self
      administered in a primary care office setting, helps identify patients at high
      risk of lung cancer. If upcoming results of randomized controlled trials show a
      benefit of lung screening, this tool could be of help to select patients for
      screening.

PMID- 19861906
TI  - Improvements in surgical results for lung cancer from 1989 to 1999 in Japan.
AB  - BACKGROUND: In 1986, Japanese Association for Thoracic Surgery started a
      nationwide survey of the number of primary lung cancer undergoing resection and
      this survey was continued annually. Thereafter, investigations of lung cancer
      surgical results have been conducted three times. The postoperative overall 5
      year survival rate was 47.8% in resected cases in 1989, 52.3% in 1994, and 62.0%
      in 1999, showing improvement over the decade (p < 0.01). OBJECTIVE: To clarify
      the factors influencing survival improvements retrospectively. PATIENTS AND
      METHODS: The subjects of the investigation are the patients who underwent
      resection for primary lung cancers in 1989, 1994, and 1999. Postoperatively,
      after 5 years, surveys of surgical results were sent to institutes where lung
      cancer resection had been performed. The subjects undergoing resection who
      provided 10 items (age, sex, pathologic T factor, pathologic N factor, pathologic
      M factor, date of resection, histology, curability, prognosis, and survival time)
      numbered 3004 in 1989, 6895 in 1994, and 12,235 in 1999. They were classified
      according to the Union International Contre le Cancer 1997 revised tumor, node,
      and metastasis classification. Differences in age, gender, histology, pathologic
      stage, curability, and operative death rates were analyzed for each survey year.
      RESULTS: According to the changes in proportions, the cases over 70 years of age,
      women, and pathologic stage I increased significantly (p < 0.001), whereas in
      cases with small cell lung cancer, incomplete resection and operative death
      decreased significantly over time (p < 0.001). CONCLUSION: The postoperative 5
      year survival rate in Japan improved between 1989 and 1999. The main cause of
      this improvement was the increase in early stage lung cancer, especially cases
      with tumors 2 cm or less in size.

PMID- 19861905
TI  - Fluorodeoxyglucose uptake measured by positron emission tomography and
      standardized uptake value predicts long-term survival of CT screening detected
      lung cancer in heavy smokers.
AB  - BACKGROUND: Fluorodeoxyglucose-positron emission tomography (FDG-PET) has proven
      its value in the diagnosis of undetermined pulmonary lesions, lung cancer
      staging, and assessment of prognosis. Purpose of this study is to clarify whether
      standardized uptake value (SUV) can predict clinical outcome of computed
      tomography (CT) screening detected lung cancer. METHODS: We tested the predictive
      value of FDG-PET using SUV on long-term survival of 34 lung cancer patients,
      detected from 1035 heavy smokers > or = 50 years monitored by annual low-dose CT
      for 5 years, with a median follow-up of 75 months from diagnosis. FINDINGS: PET
      scan was performed in 34 (89%) of 38 lung cancer patients diagnosed during the 5
      years of screening and was positive in 32 (94%). Complete resection was achieved
      in 30 cases (88%), 20 (59%) were pathologic stage I and 23 (68%) were
      adenocarcinoma. Median SUV was 5.0 overall, being significantly lower in stage I
      (2.5 vs. 10.1, p = 0.001) and in adenocarcinoma (2.5 vs. 13.0, p = 0.001). The 5
      year survival of lung cancer patients was 100% for SUV levels < or = 2.5, 60% for
      SUV more than 2.5 and less than 8, and only 20% for SUV > or = 8 (p = 0.001).
      CONCLUSIONS: FDG-PET using SUV can predict long-term survival of screening
      detected lung cancer, in a noninvasive manner. Metabolic assessment of biologic
      behavior might improve the clinical management of CT-detected lung cancer and
      reduce the risk of unnecessary treatments for indolent disease.

PMID- 19861907
TI  - Preoperative versus postoperative chemotherapy in patients with resectable non
      small cell lung cancer: systematic review and indirect comparison meta-analysis
      of randomized trials.
AB  - INTRODUCTION: A large number of trials have evaluated the efficacy of
      postoperative chemotherapy on survival after resection for lung cancer, and a
      smaller number have evaluated preoperative chemotherapy on survival for
      potentially resectable lung cancer, but no direct comparison has yet been
      published comparing the two approaches. METHODS: We conducted a systematic review
      of randomized trials, extracted time-to-event data using Parmar methods (when not
      reported), used random effects meta-analysis to evaluate overall and disease
      survival treatment effects and performed indirect comparison meta-analysis to
      obtain the relative hazards of postoperative to preoperative administration on
      survival. RESULTS: Data were abstracted from 32 randomized trials involving more
      than 10,000 participants, with 22 trials administering postoperative and 10
      trials administering preoperative chemotherapy. For overall survival, the hazard
      ratios were 0.80 (0.74-0.87; p < 0.001) and 0.81 (0.68-0.97; p = 0.024) in
      postoperative chemotherapy group and preoperative chemotherapy group,
      respectively. Using indirect comparison meta-analysis, the relative hazards of
      postoperative compared with preoperative administration was 0.99 (0.81-1.21; p =
      0.91). For disease-free survival, the hazard ratios were 0.76 (0.67-0.86; p <
      0.001) and 0.79 (0.63 to 1.00; P = 0.050) in postoperative chemotherapy group and
      preoperative chemotherapy group, respectively. Using indirect comparison meta
      analysis, the relative hazards of postoperative compared with preoperative
      administration was 0.96 (0.77-1.20; p = 0.70). CONCLUSIONS: In patients with
      resectable lung cancer, there was no evidence of a difference in overall and
      disease-free survival between the timing of administration of chemotherapy
      (postoperative versus preoperative).

PMID- 19861908
TI  - Unexpected diagnosis of pseudoaneurysmal pulmonary artery sarcoma in a patient
      with acute chest pain.

PMID- 19861909
TI  - Malignant pericardial mesothelioma with response to chemotherapy.

PMID- 19861910
TI  - Hepatic radiation injury mimicking a metastasis on positron-emission
      tomography/computed tomography in a patient with esophageal carcinoma.

PMID- 19861912
TI  - Comments on the proposed new international lymph node International Association
      for the Study of Lung Cancer map.

PMID- 19861913
TI  - Proceedings from the Ninth Annual Targeted Therapies in Lung Cancer Symposium.

PMID- 19861914
TI  - Molecular targeted therapy in non-small cell lung cancer: an overview of
      available agents.

PMID- 19861915
TI  - Intracellular signaling molecules.

PMID- 19861916
TI  - PI3 kinase, mTOR, and AKT pathways.

PMID- 19861917
TI  - Apoptosis.

PMID- 19861918
TI  - Insulin growth factor pathway.

PMID- 19861919
TI  - MET receptor tyrosine kinase.

PMID- 19861920
TI  - Fibroblastic growth factor pathway.

PMID- 19861921
TI  - DNA repair.

PMID- 19861922
TI  - Vascular endothelial growth factor pathway.

PMID- 19861923
TI  - Mitotic inhibitors.

PMID- 19861924
TI  - Protein degradation/chaperone system and histone deacetylase pathway.

PMID- 19861926
TI  - Novel cytotoxic agents.

PMID- 19861925
TI  - Cancer stem cells.

PMID- 19861927
TI  - Resistance to epidermal growth factor receptor tyrosine kinase inhibitors.

PMID- 19861928
TI  - Gene-based therapy: novel approaches.

PMID- 19861929
TI  - Physiological and anthropometric characteristics of starters and non-starters in
      junior rugby league players, aged 13-17 years.
AB  - AIM: The purpose of this study was to investigate the physical qualities of
      junior rugby league players (Under 14, 16, and 18) and determine if preseason
      fitness measures were significantly different for the players selected to play in
      the first competitive game of the season (i.e. starters) compared to the players
      not selected (i.e. non-starters). METHODS: Eighty-eight junior (N.=53 Under 14;
      N.=20 Under 16; N.=15 Under 18) subelite rugby league players participated in
      this study. All players were registered with the same junior recreational rugby
      league club. Subjects underwent measurements of anthropometry (height, body mass,
      and sum of four skinfolds), speed (10-m, 20-m, and 40-m sprint), change of
      direction speed (505 test), estimated lower body power (vertical jump), and
      estimated maximal aerobic power (multi-stage fitness test) at the beginning of
      the competitive season. RESULTS: While the relative importance of the different
      physical qualities differed between playing levels, starters tended to be taller,
      have faster change of direction speed, and greater playing experience than non
      starters. Moderate to large effect size differences were detected between
      starters and non-starters for speed and estimated maximal aerobic power results.
      CONCLUSIONS: These findings demonstrate that junior rugby league players selected
      to the starting team have better developed physical qualities than non-starting
      players. Coaches should emphasise the development of speed, change of direction
      speed, and aerobic qualities in junior rugby league players.

PMID- 19861931
TI  - Preliminary shape analysis of the outline of the baropodometric foot: patterns of
      covariation, allometry, sex and age differences, and loading variations.
AB  - AIM: Baropodometrical digital techniques map the pressures exerted on the foot
      plant during both static and dynamic loadings. The study of the distribution of
      such pressures makes it possible to evaluate the postural and locomotory
      biomechanics together with its pathological variations. This paper is aimed at
      evaluating the integration between baropodometric analysis (pressure
      distribution) and geometrical models (shape of the footprints), investigating the
      pattern of variation associated with normal plantar morphology. METHODS: The
      sample includes 91 individuals (47 males, 44 females), ranging from 5 to 85 years
      of age (mean and standard deviation = 40 + or - 24).The first component of
      variation is largely associated with the breadth of the isthmus, along a
      continuous gradient of increasing/decreasing flattening of the foot plant. This
      character being dominant upon the whole set of morphological components even in a
      non-pathological sample, such multivariate computation may represent a good
      diagnostic tool to quantify its degree of expression in individual subject or
      group samples. RESULTS: Sexual differences are not significant, and allometric
      variations associated with increasing plantar surface or stature are not
      quantitatively relevant. There are some differences between adult and young
      individuals, associated in the latter with a widening of the medial and posterior
      areas. CONCLUSIONS: These results provide a geometrical framework of
      baropodometrical analysis, suggesting possible future applications in diagnosis
      and basic research.

PMID- 19861932
TI  - Assessment of body fluid balance and voluntary drinking in ultimate players
      during a match.
AB  - AIM: Ultimate is a sport played by hundreds of thousands of people in more than
      42 countries; however, it is still mainly known as a recreational more than a
      team sport, and further studies are needed to define its physical load.
      Particularly, since no studies relating Ultimate to hydration have been
      performed, we aimed to determine body fluid balance, voluntary water intake and
      the most reliable method for assessing the hydration status of players after a
      typical 80-minute Ultimate match. METHODS: bioimpedance, urine specific gravity
      and body mass changes to asses the hydration level of the players were measured.
      RESULTS: It was observed that not all of the methods are adequate to determine
      dehydration in Ultimate players, and that measurement of body mass changes
      represents a reliable and accurate technique. CONCLUSIONS: These findings
      demonstrate that ultimate as an intense sport that can induce significant fluid
      loss, which is not always replaced by individual drinking.

PMID- 19861930
TI  - Prediction of maximal oxygen uptake by bioelectrical impedance analysis in
      overweight adolescents.
AB  - AIM: Maximal oxygen uptake (VO(2max)), the gold standard for measurement of
      cardiorespiratory fitness, is frequently difficult to assess in overweight
      individuals due to physical limitations. Reactance and resistance measures
      obtained from bioelectrical impedance analysis (BIA) have been suggested as
      easily obtainable predictors of cardiorespiratory fitness, but the accuracy with
      which ht(2)/Z can predict VO(2max) has not previously been examined in overweight
      adolescents. METHODS: The impedance index was used as a predictor of VO(2max) in
      87 overweight girls and 47 overweight boys ages 12 to 17 with mean BMI of 38.6 +
      or - 7.3 and 42.5 + or - 8.2 in girls and boys respectively. The Bland Altman
      procedure assessed agreement between predicted and actual VO(2max). RESULTS:
      Predicted VO(2max) was significantly correlated with measured VO(2max)
      (r(2)=0.48, P<0.0001). Using the Bland Altman procedure, there was significant
      magnitude bias (r(2)=0.10; P<0.002). The limits of agreement for predicted
      relative to actual VO(2max) were -589 to 574 mL O(2)/min. CONCLUSIONS: The
      impedance index was highly correlated with VO(2max) in overweight adolescents.
      However, using BIA data to predict maximal oxygen uptake over-predicted VO(2max)
      at low levels of oxygen consumption and under-predicted VO(2max) at high levels
      of oxygen consumption. This magnitude bias, along with the large limits of
      agreement of BIA-derived predicted VO(2max), limit its usefulness in the clinical
      setting for overweight adolescents.

PMID- 19861933
TI  - Wearing a cap, thermoregulation, and thermal sensation during running in a hot
      environment.
AB  - AIM: The aim of this study was to determine if wearing a cap negatively alters
      thermoregulation or thermal sensation during prolonged running in the heat.
      METHODS: Nine well-trained runners ran for 1 hour at 67% VO(2)max in a hot
      environment (T(a) =31 degrees Celsius, RH=41%) wearing (CAP) or not wearing
      (NOCAP) a white cotton/polyester running cap. During both running trials,
      subjects consumed 2 mL x kg(-1) of cold water every 15 minutes. Thermal balance
      was assessed using rectal (T(re)) and skin temperatures (T(sk)) as well as
      measurement of whole-body sweat loss and thermal sensation of the head and of the
      overall body (8-point scale). RESULTS: There were no significant differences in
      T(re), T(sk) or whole-body sweat loss between conditions. When compared to NOCAP,
      forehead skin temperature increased more during CAP (P<0.05). Although there were
      no differences in ratings of thermal sensation of the overall body between
      treatments, ratings of thermal sensation of the head were higher (P<0.05) during
      CAP. There were no differences in heart rate or rating of perceived exertion
      between conditions. CONCLUSIONS. Despite higher ratings of thermal sensation of
      the head and higher forehead skin temperatures when wearing a cap during
      prolonged running in the heat, thermoregulation was not otherwise negatively
      altered.

PMID- 19861934
TI  - Comparative study of clinical and ultrasonographic evaluation of lateral
      collateral ligament sprains of the ankle.
AB  - AIM: Clinical examination is sometimes insufficient to assess the severity of
      lateral collateral ligament (LCL) sprain of the ankle, making it difficult to
      choose the most appropriate treatment. The aim of this study was to compare the
      assessment of clinical signs and the ultrasonographic findings in recent LCL
      sprain of the ankle. METHODS: This was a retrospective cross-sectional study.
      Spearman's rank correlation test and multiple regression analysis were used to
      assess correlations between clinical signs and type of ligament injury. Fisher's
      linear discriminant analysis was used to determine most contributive signs in
      ligament tear diagnosis. RESULTS: No single clinical sign was correlated with the
      severity of ligament injury as revealed by ultrasonography in the 34 patients
      analyzed. Careful assessment of all the usual clinical signs of severity seems to
      better guide the diagnosis of the presence or absence of ligament tearing.
      CONCLUSIONS: These results confirm the lack of correlation between clinical
      examination and the anatomic injury in distension or partial tearing of the
      anterior talofibular ligament. They raise questions about the usefulness of
      clinical classifications and suggest a broadening of the indications for
      ultrasonographic exam in ambiguous situations, particularly for athletes showing
      few signs of severe injury, in order to ensure optimal treatment and a faster
      recovery.

PMID- 19861935
TI  - Spontaneous Achilles tendon ruptures treated with a mini-open technique: clinical
      and functional evaluation.
AB  - AIM AND METHODS: Spontaneous ruptures of the Achilles tendon are frequent among
      occasional and high level athletes. Despite the frequency of this problem, there
      is no agreement about the treatment of this pathology. The purpose of this study
      was to show the results of 20 consecutive patients (14 males and 6 females)
      surgically treated between 1995 and 2001 with a mini-open technique (mean follow
      up: 52 months; range 20-95 months). Postoperatively, all these patients were
      assessed with a new functional scoring scale and a functional jumping test (Ergo
      Jump Bosco System). RESULTS: A very low rate of minor complications have been
      reported and most of these patients are now practicing their favoured sport at
      the same pre-injury level. CONCLUSIONS: Mini open repair should be considered an
      excellent method of treatment of this pathology, with a very low rate of
      complications. The authors recommend this technique for young professional and
      occasional athletes.

PMID- 19861936
TI  - Prevalence of low back pain in former rhythmic gymnasts.
AB  - AIM: It is still debated as to whether rhythmic gymnastics is a discipline at
      risk of low back pain, because the concern for the extreme and repetitive
      hyperextension of the column may be counteracted by protective factors which are
      distinctive of rhythmic gymnasts, namely: leanness, lumbar flexibility and muscle
      strength. This study aimed to assess the prevalence of low back pain in a cohort
      of former elite-level rhythmic gymnasts of the Rhythmic Gymnastics National Team.
      METHODS: The Study Group included 60 adult females who were former rhythmic
      gymnasts of the Italian National Team. The Control Group included 60 adult
      females comparable for age, who were never involved in high level sport
      competitions. A standardized questionnaire was used to evaluate low back-pain
      symptoms. RESULTS: Low back pain complaints were reported by 22 former rhythmic
      gymnasts and by 28 controls (36.6% vs. 46.6%, p: n.s.); in the ex-gymnasts the
      age of onset of pain was earlier than in controls. The former rhythmic gymnasts
      complaining low back pain reported a higher prevalence of symptoms also during
      the time of competitions, and retired earlier than those without pain.
      CONCLUSIONS: Former elite rhythmic gymnasts reported a prevalence of low back
      pain similar to sex and age matched general population. However, the rhythmic
      gymnasts who complained back pain during the sport activity are at risk of an
      early onset of symptoms after the retire from competitions. This study suggests
      that rhythmic gymnastics is not associated with increased risk of low back pain
      in the adult age.

PMID- 19861937
TI  - Salivary hormonal responses to resistance exercise in trained and untrained
      middle-aged men.
AB  - AIM: The aim of the present study was to investigate if there are differences in
      salivary hormonal responses to resistance exercise between long-term strength
      trained and untrained men. METHODS: Twenty-eight subjects were recruited to this
      study, matched into a strength-trained group (SG, N=13) and an untrained group
      (UG, N=15). Upper and lower body absolute muscle strength was measured through
      the one-repetition maximum (1-RM) test. Saliva samples were collected at rest and
      after a resistance exercise protocol (REP) with intensity relative to 1-RM
      values. With these samples, testosterone (TES), dehydroepiandrosterone (DHEA) and
      cortisol (COR) were determined. RESULTS: SG subjects demonstrated significantly
      higher values in all muscle strength variables. While a significant increase in
      TES after REP was found in the SG (0.114 + or - 0.1 vs. 0.15 + or - 0.09 pg/mL,
      P<0.05), no differences were observed in the UG (0.144 + or - 0.1 vs. 0.17 + or -
      0.1 pg/mL). In both groups, there were increases in salivary COR (SG: 1.4 + or -
      0.6 vs. 2.06 + or - 1; UG: 1.5 + or - 0.8 vs. 2.3 + or - 1.2 ug/dL, P<0.05) and
      DHEA (SG: 0.6 + or - 0.3 vs. 0.9 + or - 0.6; UG: 0.65 + or - 0.3 vs. 0.97 + or -
      0.7 ng/dL, P<0.05). CONCLUSIONS: These results suggest the possible presence of
      adaptation of TES responses to resistance exercise in long-term strength-trained
      men, with these subjects presenting higher responses to the same stimulus,
      compared with untrained subjects, while no such adaptation was seen at the
      adrenocortical level in these subjects as the responses observed were similar in
      both groups.

PMID- 19861938
TI  - Soluble transferrin receptor values in top level soccer players and skiers:
      comparison with sedentary people and pitfalls of laboratory methods.
AB  - AIM: Hematological assessment is crucial in athletes: the risk of sports' anemia
      should be monitored with hematological parameters and iron metabolism tests. The
      aim of this study was to evaluate soluble transferrin receptor (sTfR) efficacy,
      as it is highly sensitive and specific and usually utilized in sport medicine for
      monitoring iron metabolism. METHODS: sTfR was studied using two immunological
      methods (IDeA Orion, and Biokit) on a group of professional athletes, together
      with hematological and iron metabolism parameters. Values have been compared with
      those of sedentary people, before and during competitive season. Athletes were 76
      professional male soccer players plus 20 males and 14 females of the alpine ski
      Italian National Teams. RESULTS: The sTfR values in athletes are similar to those
      found in sedentary people. Different results have been observed between the two
      different methods: a bias of 0.37 mg/L was found comparing them. A significant
      correlation between sTfR and iron, transferrin saturation, and reticulocytes was
      found in skiers; there was no correlation with hemoglobin, erythrocytes,
      ferritin. In soccer players significant differences have been retrieved among
      different teams' distribution of data. CONCLUSIONS: The principal limit for using
      sTfR in sports medicine, but also in the general population, is the lack of
      standardization among methods. The quantitative differences in athletes between
      the two methods are high, although the behavior of the parameter is similar from
      the quality point of view. The differences between measured concentrations could
      influence the thresholds used in antidoping context.

PMID- 19861939
TI  - Exercise in, and adaptations to a cold environment have no effect on SIgA.
AB  - AIM: The authors hypothesized that inconsistent SIgA response to exercise is
      caused by the different adaptative status of subjects to a cold environment. The
      purposes of the study were to examine whether moderate-intense exercise in a cold
      environment decreases SIgA and whether adaptation to a cold environment has any
      effect on SIgA. METHODS: Young male skaters, short track (N=9) and inline (N=10),
      participated in this study. All subjects cycled for 60 min at 65% VO(2max) in
      cold (ambient temperature: 5 +or - 1 degrees Celsius, relative humidity 41 + or -
      9%) and thermoneutral (ambient temperature: 21 + or - 1 degrees Celsius, relative
      humidity 35 + or - 5%) conditions. Saliva samples were collected as follows:
      before and after 1hour of environmental exposure; immediately, 30-min, 60-min and
      120-min after the exercise. RESULTS AND CONCLUSIONS: Salivary SIgA and saliva
      flow rate decreased after the exercise in both groups only in thermoneutral
      conditions. The SIgA secretion rate did not decrease after moderate-high
      intensity exercise in a cold environment, and the SIgA response to exercise was
      not affected by the different adaptative status of subjects to the cold
      environment.

PMID- 19861940
TI  - Muscle morphology and jump performance: gender and intermuscular variability.
AB  - AIM: The present study aimed 1) to investigate the gender differences in jump
      performance and muscle architecture between men and women; and 2) to determine
      whether the differences in jump performance could be attributed to gender
      differences in the muscle architecture of the leg extensor muscles. METHODS:
      Sixty-two subjects volunteered for the study (34 women and 28 men): 19 club-level
      volleyball players, 20 physical education students, and 23 sedentary individuals.
      They performed trials of countermovement jumps (CMJ) and the muscle architecture
      of the vastus lateralis (VL), gastrocnemius medialis (GM), and lateralis (GL)
      were analyzed at rest by ultrasonography. RESULTS: There were significant
      differences in jump performance between men and women (CMJ height: 0.388 + or -
      0.056 m in men and 0.279 + or - 0.060 m in women, P<0.001). There were also
      significant gender differences in the VL muscle thickness, while the relative
      fascicle length was significantly different in the three muscles studied, with
      longer fascicles in the VL muscle in men and longer fascicles in the gastrocnemii
      in women. There were significant associations between the VL muscle size and jump
      performance (r=0.49-0.50, P<0.001), and non linear relationships between muscle
      size parameters and pennation angles (R(2)=0.67-0.77, P<0.001). CONCLUSIONS:
      These results confirm that there are gender differences in the muscle
      architecture of people with a wide physical activity background. The gender
      differences found in the VL muscle size partially explained the differences in
      jump performance.

PMID- 19861941
TI  - Shuttle swim test for water polo players: validity and reliability.
AB  - AIM: The purpose of this study, carried out on elite water polo players, was to
      examine: 1) the relationship between the shuttle swim test (SST) and the
      performance during official water polo games, and 2) the SST reliability.
      METHODS: Sixteen male players of the Italian National Water Polo Team (age: 27.9
      + or - 2.1 years, body mass: 88.5 + or - 10.3 kg, height: 186.6 + or - 6.9 cm)
      performed the SST, consisting of two sets of seven repetitions from 40 to 10 m
      (total of 120 m for each set) at a maximal intensity with 90 s of rest between
      sets. During the SST, average swimming speed, blood lactate concentration and
      heart rate were recorded. Direct validity of the SST was evaluated by comparing
      the average swimming speed with the total distance covered (TD) and the distance
      covered at high intensity swimming (above 1.8 m x s(-1), HIS) during three
      official water polo games. SST reliability was assessed by testing the same
      athletes one week apart. RESULTS: Average swimming speed during the SST was
      significantly correlated with TD (r=0.67, P<0.01) and HIS (r=0.74, P<0.004). The
      mean average speed during SST showed high reliability (TE=0.4%; CI 95%: 0.2% to
      1.0% ). The T1 vs. T2 difference in mean average speed was not significant.
      CONCLUSIONS: Present findings demonstrate the validity and reliability of the SST
      for evaluation of the swimming fitness of water polo players.

PMID- 19861942
TI  - Isolation and large scale expansion of adult human endothelial colony forming
      progenitor cells.
AB  - This paper introduces a novel recovery strategy for endothelial colony forming
      progenitor cells (ECFCs) from heparinized but otherwise unmanipulated adult human
      peripheral blood within a mean of 12 days. After large scale expansion >1x10(8)
      ECFCs can be obtained for further tests. Advantageously by using pHPL the contact
      of human cells with bovine serum antigens can be excluded. By flow cytometry and
      immunohistochemistry the isolated cells can be characterized as ECFC and their in
      vitro functionality to form vascular like structures can be tested in a matrigel
      assay. Further these cells can be subcutaneously injected in a mouse model to
      form functional, perfused vessels in vivo. After long term expansion and
      cryopreservation proliferation, function and genomic stability appear to be
      preserved. (3,4) This animal-protein free isolation and expansion method is
      easily applicable to generate a large quantity of ECFCs.

PMID- 19861943
TI  - Affirmative action at the NIH.

PMID- 19861945
TI  - Any kind of mother in a storm.

PMID- 19861946
TI  - How to button a bouton with alpha2deltas.

PMID- 19861947
TI  - Optimizing brain processing.

PMID- 19861948
TI  - AAV8-mediated gene therapy prevents induced biochemical attacks of acute
      intermittent porphyria and improves neuromotor function.
AB  - Acute intermittent porphyria (AIP), an autosomal dominant hepatic porphyria due
      to half-normal hydroxymethylbilane synthase (HMB-synthase) activity, is
      manifested by life-threatening acute neurological attacks that are precipitated
      by factors that induce heme biosynthesis. The acute attacks are currently treated
      with intravenous hemin, but a more continuous therapy is needed, particularly for
      patients experiencing frequent attacks. Thus, a recombinant AAV8-based serotype
      vector expressing murine HMB-synthase driven by liver-specific regulatory
      elements was generated and its effectiveness to prevent the biochemical induction
      of an acute attack was evaluated in an AIP mouse model. Intraperitoneal
      administration of the adeno-associated viral (AAV) vector resulted in a rapid and
      dose-dependent increase of HMB-synthase activity that was restricted to the
      liver. Stable expression of hepatic HMB-synthase was achieved and wild-type or
      greater levels were sustained for 36 weeks. When heme synthesis was periodically
      induced by a series of phenobarbital injections, the treated mice did not
      accumulate urinary delta-aminolevulinic acid (ALA) or porphobilinogen (PBG),
      indicating that the expressed enzyme was functional in vivo and prevented
      induction of the acute attack. Further, rotarod performance and footprint
      analyses improved significantly. Thus, liver-directed gene therapy provided
      successful long-term correction of the hepatic metabolic abnormalities and
      improved neuromotor function in the murine model of human AIP.

PMID- 19861950
TI  - Systematic evaluation of AAV vectors for liver directed gene transfer in murine
      models.
AB  - Vectors based on adeno-associated viruses (AAVs) are being evaluated for use in
      liver-directed gene therapy. Candidates have been preselected on the basis of
      capsid structure that plays an important role in determining performance
      profiles. We describe a comprehensive and statistically powered set of mouse
      studies designed to compare the performance of vectors based on seven novel AAV
      capsids. The key criteria used to select candidates for successful gene therapy
      are high level and stable transgene expression in the absence of toxicity. Based
      on these criteria, the best performing vectors, AAV8, AAVhu.37, and AAVrh.8, will
      be further evaluated in nonhuman primates (NHPs).

PMID- 19861949
TI  - Long-term physiologically regulated expression of the low-density lipoprotein
      receptor in vivo using genomic DNA mini-gene constructs.
AB  - Familial hypercholesterolemia (FH) is a condition caused by mutations in the low
      density lipoprotein receptor (LDLR) gene. Expression of LDLR is highly regulated
      and excess receptor expression is cytotoxic. To incorporate essential gene
      regulation into a gene therapy vector for FH, we generated vectors in which the
      expression of therapeutic human LDLR gene, or luciferase reporter gene, is driven
      by 10 kb of human LDLR genomic DNA encompassing the promoter region including
      elements essential for physiologically regulated expression. Using luciferase
      expression and specific LDL binding and internalization assays, we have shown in
      vitro that the genomic promoter element confers long-term, physiologically
      regulated gene expression and complementation of receptor deficiency in culture
      for 240 cell-generations. This was demonstrated in the presence of sterols or
      statins, modifiers of LDLR promoter activity. In vivo, we demonstrate efficient
      liver-specific delivery and expression of luciferase following hydrodynamic tail
      vein injection and confirm that expression from the LDLR promoter element is
      sensitive to statin administration. We also demonstrate long-term LDLR expression
      from the 10-kb promoter element up to 9 months following delivery. The vector
      system that we describe provides the efficient delivery, long-term expression,
      and physiological regulation required for a successful gene therapy intervention
      for FH.

PMID- 19861951
TI  - Long-term rescue of a lethal murine model of methylmalonic acidemia using adeno
      associated viral gene therapy.
AB  - Methylmalonic acidemia (MMA) is an organic acidemia caused by deficient activity
      of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). This disorder is
      associated with lethal metabolic instability and carries a poor prognosis for
      long-term survival. A murine model of MMA that replicates a severe clinical
      phenotype was used to examine the efficacy of recombinant adeno-associated virus
      (rAAV) serotype 8 gene therapy as a treatment for MMA. Lifespan extension, body
      weight, circulating metabolites, transgene expression, and whole animal
      propionate oxidation were examined as outcome parameters after gene therapy. One
      hundred percent of the untreated Mut(-/-) mice (n = 58) died by day of life (DOL)
      72, whereas >95% of the adeno-associated virus-treated Mut(-/-) mice (n = 27)
      have survived for > or = 1 year. Despite a gradual loss of transgene expression
      and elevated circulating metabolites in the treated Mut(-/-) mice, the animals
      are indistinguishable from unaffected control littermates in size and activity
      levels. These experiments provide the first definitive evidence that gene therapy
      will have clinical utility in the treatment of MMA and support the development of
      gene therapy for other organic acidemias.

PMID- 19861952
TI  - Overexpression of sonic Hedgehog in the lung mimics the effect of lung injury and
      compensatory lung growth on pulmonary Sca-1 and CD34 positive cells.
AB  - Cells localized in the bronchioalveolar duct junction of the murine lung have
      been identified as potential bronchioalveolar stem cells. Based on the surface
      marker expression, two main phenotypes have been proposed: Sca-1(+), CD34(+),
      CD45(-), Pecam(-) and Sca-1(low), CD34(-) CD45(-), Pecam(-) cells. An increase in
      the number of Sca-1(+), CD34(+) CD45(-), Pecam(-) cells and activation of the
      sonic hedgehog (Shh) pathway was observed following unilateral pneumonectomy and
      naphthalene-induced airway injury. Overexpression of Shh in the respiratory tract
      also resulted in an increase of this cell population. Syngeneic transplantation
      of beta-galactosidase-expressing bone marrow cells demonstrated that the increase
      of Sca-1(+), CD34(+), CD45(-), Pecam(-) cells in the lung was a result of local
      proliferation. Intratracheal administration of purified Shh-stimulated Sca-1(+),
      CD45(-), Pecam(-) cells coexpressing CD34 to syngeneic mice following
      pneumonectomy resulted in engraftment of these cells predominantly in the airways
      for up to 3 months, whereas Sca-1(-), CD45(-), Pecam(-) cells did not engraft.
      This study suggests that local Sca-1(+), CD34(+), CD45(-), Pecam(-) cells are
      stimulated during compensatory lung growth, following airway injury and
      overexpression of Shh and have some potential to engraft in the airways, without
      showing clonal properties in vivo.

PMID- 19861953
TI  - The natural history of adult Crohn's disease in population-based cohorts.
AB  - OBJECTIVES: Natural history studies provide invaluable data on the disease
      course. First, they help define the end points for clinical trials that are
      designed to test drugs for the end point of disease modification in chronic
      disabling diseases. Natural history studies can also help to identify subsets of
      patients in whom the disease prognosis can be stratified according to clinical
      features. This comprehensive review summarizes our current knowledge of the
      natural history of Crohn's disease in adults as reported in population-based
      studies that include long-term follow-up results. METHODS: We conducted a
      literature search of English and non-English language publications listed in the
      electronic databases of MEDLINE (source PUBMED, 1935 to December 2008). RESULTS:
      One-third of the patients had ileitis, colitis, or ileocolitis at the time of
      diagnosis. Disease location remained broadly stable over time. Up to one-third of
      the patients had evidence of a stricturing or penetrating intestinal complication
      at diagnosis, and half of all patients had experienced an intestinal complication
      within 20 years after diagnosis. Ten percent of the patients had prolonged
      clinical remission. Steroid dependency occurred in one-third of the patients, and
      surgery was required in one-third after initiation of steroid therapy. The annual
      incidence of hospitalizations was 20%. Half of the patients required surgery
      within 10 years after diagnosis. The risk of postoperative recurrence was 44-55%
      after 10 years. CONCLUSIONS: Crohn's disease is a disabling condition over time.
      The impact of changing treatment paradigms with increased use of
      immunosuppressants and biological agents on its natural history is poorly known.

PMID- 19861954
TI  - Comparison of BISAP, Ranson's, APACHE-II, and CTSI scores in predicting organ
      failure, complications, and mortality in acute pancreatitis.
AB  - OBJECTIVES: Identification of patients at risk for severe disease early in the
      course of acute pancreatitis (AP) is an important step to guiding management and
      improving outcomes. A new prognostic scoring system, the bedside index for
      severity in AP (BISAP), has been proposed as an accurate method for early
      identification of patients at risk for in-hospital mortality. The aim of this
      study was to compare BISAP (blood urea nitrogen >25 mg/dl, impaired mental
      status, systemic inflammatory response syndrome (SIRS), age>60 years, and pleural
      effusions) with the "traditional" multifactorial scoring systems: Ranson's, Acute
      Physiology and Chronic Health Examination (APACHE)-II, and computed tomography
      severity index (CTSI) in predicting severity, pancreatic necrosis (PNec), and
      mortality in a prospective cohort of patients with AP. METHODS: Extensive
      demographic, radiographic, and laboratory data from consecutive patients with AP
      admitted or transferred to our institution was collected between June 2003 and
      September 2007. The BISAP and APACHE-II scores were calculated using data from
      the first 24 h from admission. Predictive accuracy of the scoring systems was
      measured by the area under the receiver-operating curve (AUC). RESULTS: There
      were 185 patients with AP (mean age 51.7, 51% males), of which 73% underwent
      contrast-enhanced CT scan. Forty patients developed organ failure and were
      classified as severe AP (SAP; 22%). Thirty-six developed PNec (19%), and 7 died
      (mortality 3.8%). The number of patients with a BISAP score of > or =3 was 26;
      Ranson's > or =3 was 47, APACHE-II > or =8 was 66, and CTSI > or =3 was 59. Of
      the seven patients that died, one had a BISAP score of 1, two had a score of 2,
      and four had a score of 3. AUCs for BISAP, Ranson's, APACHE-II, and CTSI in
      predicting SAP are 0.81 (confidence interval (CI) 0.74-0.87), 0.94 (CI 0.89
      0.97), 0.78 (CI 0.71-0.84), and 0.84 (CI 0.76-0.89), respectively. CONCLUSIONS:
      We confirmed that the BISAP score is an accurate means for risk stratification in
      patients with AP. Its components are clinically relevant and easy to obtain. The
      prognostic accuracy of BISAP is similar to those of the other scoring systems. We
      conclude that simple scoring systems may have reached their maximal utility and
      novel models are needed to further improve predictive accuracy.

PMID- 19861955
TI  - Diarrhea-predominant irritable bowel syndrome is associated with diverticular
      disease: a population-based study.
AB  - OBJECTIVES: A subset of patients with colonic diverticular disease have chronic
      gastrointestinal symptoms, and some have a clinical diagnosis of irritable bowel
      syndrome (IBS), but whether IBS and diverticular disease are linked is uncertain.
      We aimed to evaluate this association in the community. METHODS: A population
      based, cross-sectional survey was conducted by mailing a valid symptom
      questionnaire to the eligible residents of Olmsted County, MN, aged 30-95 years.
      Colonic diverticular disease (diverticulosis and diverticulitis) was ascertained
      through a review of the complete medical history of all responders. Subjects with
      at least one relevant test (colonoscopy, computed tomography (CT) scan, CT
      colonography, or barium enema) were included. IBS was defined using Rome II
      criteria. RESULTS: Among 2,267 eligible respondents, there were 1,712 subjects
      who had undergone colon testing (76%): 919 women (54%); mean (+/-s.d.) age 65 (+/
      11 years). Colonic diverticular disease was identified in 44.4% (95% confidence
      interval (CI) 42.1-46.8) of the subject. IBS was reported by 8.8% (95% CI 6.9
      11.0) of men and 17.0% (95% CI 14.6-19.6) of women. After adjusting for age and
      gender, the presence of IBS was associated with an increased odds for
      diverticulosis (odds ratio (OR) =1.8, 95% CI 1.3-2.4) but not diverticulitis
      (OR=1.7, 95% CI 0.9-3.2). In those 65 years of age or older, the presence of IBS
      was associated with a ninefold higher odds for diverticulosis (OR=9.4, 95% CI 5.8
      15.1). Relative to the non-IBS subgroup, diarrhea-predominant IBS and mixed IBS
      were significantly associated with an increased odds for diverticular disease
      (OR=1.9, 95% CI 1.1-3.2; OR=2.6, 95% CI 1.0-6.4, respectively). CONCLUSIONS:
      There is a significantly increased odds for colonic diverticulosis in subjects
      with IBS (relative to those without IBS). These results suggest that IBS and
      colonic diverticular disease may be connected.

PMID- 19861956
TI  - No change in rectal sensitivity after gut-directed hypnotherapy in children with
      functional abdominal pain or irritable bowel syndrome.
AB  - OBJECTIVES: Gut-directed hypnotherapy (HT) has recently been shown to be highly
      effective in treating children with functional abdominal pain (FAP) and irritable
      bowel syndrome (IBS). This study was conducted to determine the extent to which
      this treatment success is because of an improvement in rectal sensitivity.
      METHODS: A total of 46 patients (aged 8-18 years) with FAP (n=28) or IBS (n=18)
      were randomized to either 12 weeks of standard medical therapy (SMT) or HT. To
      assess rectal sensitivity, a pressure-controlled intermittent distension protocol
      (barostat) was performed before and after the therapy. RESULTS: Rectal
      sensitivity scores changed in SMT patients from 15.1+/-7.3 mm Hg at baseline to
      18.6+/-8.5 mm Hg after 12 weeks of treatment (P=0.09) and in HT patients from
      17.0+/-9.2 mm Hg to 22.5+/-10.1 mm Hg (P=0.09). The number of patients with
      rectal hypersensitivity decreased from 6 of 18 to 0 of 18 in the HT group
      (P=0.04) vs. 6 of 20 to 4 of 20 in the SMT group (P=0.67). No relationship was
      established between treatment success and rectal pain thresholds. Rectal
      sensitivity scores at baseline were not correlated with intensity, frequency, or
      duration of abdominal pain. CONCLUSIONS: Clinical success achieved with HT cannot
      be explained by improvement in rectal sensitivity. Furthermore, no association
      could be found between rectal barostat findings and clinical symptoms in children
      with FAP or IBS. Further studies are necessary to shed more light on both the
      role of rectal sensitivity in pediatric FAP and IBS and the mechanisms by which
      hypnotherapy results in improvement of clinical symptoms.

PMID- 19861957
TI  - PML nuclear body component Sp140 is a novel autoantigen in primary biliary
      cirrhosis.
AB  - OBJECTIVES: Some patients with primary biliary cirrhosis (PBC) have antinuclear
      antibodies (ANAs). These ANAs include the "multiple nuclear dots" (MND) staining
      pattern, targeting promyelocytic leukemia protein (PML) nuclear body (NB)
      components, such as "speckled 100-kD" protein (Sp100) and PML. A new PML NB
      protein, designated as Sp140, was identified using serum from a PBC patient. The
      aim of this study was to analyze the immune response against Sp140 protein in PBC
      patients. METHODS: We studied 135 PBC patients and 157 pathological controls with
      type 1 autoimmune hepatitis, primary sclerosing cholangitis, and systemic lupus
      erythematosus. We used indirect immunofluorescence and a neuroblastoma cell line
      expressing Sp140 for detecting anti-Sp140 antibodies, and a commercially
      available immunoblot for detecting anti-Sp100 and anti-PML antibodies. RESULTS:
      Anti-Sp140 antibodies were present in 20 (15%) PBC patients but not in control
      samples, with a higher frequency in antimitochondrial antibody (AMA)-negative
      cases (53 vs. 9%, P<0.0001). Anti-Sp140 antibodies were found together with anti
      Sp100 antibodies in all but one case (19 of 20, 90%) and with anti-PML antibodies
      in 12 (60%) cases. Anti-Sp140 positivity was not associated with a specific
      clinical feature of PBC. CONCLUSIONS: Our study identifies Sp140 as a new, highly
      specific autoantigen in PBC for the first time. The very frequent coexistence of
      anti-Sp140, anti-Sp100 and anti-PML antibodies suggests that the NB is a
      multiantigenic complex in PBC and enhances the diagnostic significance of these
      reactivities, which are particularly useful in AMA-negative cases.

PMID- 19861958
TI  - Genetic analysis in a Dutch study sample identifies more ulcerative colitis
      susceptibility loci and shows their additive role in disease risk.
AB  - OBJECTIVES: Genetic susceptibility is known to make a major contribution to the
      pathogenesis of ulcerative colitis (UC). Recently, three studies, including a
      genome-wide association study (GWAS), reported novel UC risk loci. METHODS: The
      top-20 single-nucleotide polymorphisms (SNPs) from the first UC-GWAS were
      genotyped, as part of the study's replication phase, in 561 UC cases and 728
      controls from our Dutch UC study sample. We genotyped eight SNPs identified in
      two more studies, in these individuals, and replicated all significantly
      associated SNPs in an additional 894 UC cases and 1,174 controls from our Dutch
      UC study sample. A combined analysis for all patients (n=1,455) and controls
      (n=1,902) was performed. Dose-response models were constructed with the
      associated risk alleles. RESULTS: We found 12 SNPs tagging ten loci, including
      HLA-DRA, IL10, IL23R, JAK2, S100Z, ARPC2, and ECM1, to be associated with UC. We
      identified 10q26, flagged by the UC-GWAS but not confirmed in its replication
      phase, as a UC locus and found a trend toward association for GAS7. No
      association with disease localization or severity was found. The dose-response
      models show that individuals carrying 11 or more risk alleles have an odds ratio
      of 8.2 (confidence interval 3.0-22.8) for UC susceptibility. CONCLUSIONS: We
      confirmed the association of multiple loci with UC in the Dutch population and
      found evidence for association of 10q26 and a trend suggesting association for
      GAS7. Genetic models show that multiple risk loci in an individual increase the
      risk for developing UC.

PMID- 19861959
TI  - Predicting fibrosis worsening in obese patients with NASH through parenchymal
      fibronectin, HOMA-IR, and hypertension.
AB  - OBJECTIVES: Few published studies have examined the results obtained from repeat
      liver biopsies in obese patients with nonalcoholic fatty liver disease (NAFLD).
      The progressive form of this disease may be largely limited to a subgroup of
      NAFLD patients with nonalcoholic steatohepatitis (NASH). The presence of
      intralobular fibronectin (Fn) and other variables was investigated in relation to
      subsequent fibrosis progression. METHODS: In this prospective study, 271 obese
      patients admitted to the hospital with NAFLD and abnormal liver enzymes were
      scheduled to undergo a repeat liver biopsy at least 5 years after the initial
      biopsy. After excluding cirrhotic patients, basal biopsy specimens obtained from
      patients who underwent a second liver biopsy were stained with antibodies against
      Fn. The progression of fibrosis in the follow-up sample was correlated with the
      amount of Fn and other clinicopathological variables. RESULTS: We obtained a
      second liver biopsy from 149 patients after a median time of 6.4 years. Of these,
      132 showed suitable Fn staining for semi-quantitative assessments. In all, 44 out
      of 83 patients (53%) with basal NASH showed fibrosis progression by at least one
      stage in the second liver biopsy. The amount of Fn (odds ratio=14.1; P<0.001), a
      diagnosis of hypertension (odds ratio=4.8; P=0.028), and homeostasis model
      assessment parameter of insulin resistance (HOMA-IR) scores (>8, odds ratio=1.9;
      P=0.004) were independent predictive factors of worsening fibrosis. CONCLUSIONS:
      A semi-quantitative assessment of the amount of parenchymal Fn present at an
      early stage in obese patients with NASH is valuable for predicting the
      progression of fibrosis. Similarly, lobular Fn deposition may be a sensitive and
      early indicator of active fibrogenetic processes in the liver. Hypertension and
      higher HOMA-IR scores are other clinical independent risk factors that predict
      the progression of fibrosis.

PMID- 19861960
TI  - Activity of the multikinase inhibitor dasatinib against ovarian cancer cells.
AB  - BACKGROUND: Here, we explore the therapeutic potential of dasatinib, a small
      molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine
      kinases, including members of the Src kinase family, EphA2, and focal adhesion
      kinase for the treatment of ovarian cancer. METHODS: We examined the effects of
      dasatinib on proliferation, invasion, apoptosis, cell-cycle arrest, and kinase
      activity using a panel of 34 established human ovarian cancer cell lines.
      Molecular markers for response prediction were studied using gene expression
      profiling. Multiple drug effect/combination index (CI) isobologram analysis was
      used to study the interactions with chemotherapeutic drugs. RESULTS:
      Concentration-dependent anti-proliferative effects of dasatinib were seen in all
      ovarian cancer cell lines tested, but varied significantly between individual
      cell lines with up to a 3 log-fold difference in the IC(50) values (IC(50) range:
      0.001-11.3 micromol l(-1)). Dasatinib significantly inhibited invasion, and
      induced cell apoptosis, but less cell-cycle arrest. At a wide range of clinically
      achievable drug concentrations, additive and synergistic interactions were
      observed for dasatinib plus carboplatin (mean CI values, range: 0.73-1.11) or
      paclitaxel (mean CI values, range: 0.76-1.05). In this study, 24 out of 34 (71%)
      representative ovarian cancer cell lines were highly sensitive to dasatinib,
      compared with only 8 out of 39 (21%) representative breast cancer cell lines
      previously reported. Cell lines with high expression of Yes, Lyn, Eph2A, caveolin
      1 and 2, moesin, annexin-1, and uPA were particularly sensitive to dasatinib.
      CONCLUSIONS: These data provide a clear biological rationale to test dasatinib as
      a single agent or in combination with chemotherapy in patients with ovarian
      cancer.

PMID- 19861961
TI  - Tumour-targeted delivery of TRAIL using Salmonella typhimurium enhances breast
      cancer survival in mice.
AB  - BACKGROUND: An effective cancer therapeutic must selectively target tumours with
      minimal systemic toxicity. Expression of a cytotoxic protein using Salmonella
      typhimurium would enable spatial and temporal control of delivery because these
      bacteria preferentially target tumours over normal tissue. METHODS: We engineered
      non-pathogenic S. typhimurium to secrete murine TNF-related apoptosis-inducing
      ligand (TRAIL) under the control of the prokaryotic radiation-inducible RecA
      promoter. The response of the RecA promoter to radiation was measured using
      fluorometry and immunoblotting. TRAIL toxicity was determined using flow
      cytometry and by measuring caspase-3 activation. A syngeneic murine tumour model
      was used to determine bacterial accumulation and the response to expressed TRAIL.
      RESULTS: After irradiation, engineered S. typhimurium secreted TRAIL, which
      caused caspase-3-mediated apoptosis and death in 4T1 mammary carcinoma cells in
      culture. Systemic injection of Salmonella and induction of TRAIL expression using
      2 Gy gamma-irradiation caused a significant delay in mammary tumour growth and
      reduced the risk of death by 76% when compared with irradiated controls. Repeated
      dosing with TRAIL-bearing Salmonella in conjunction with radiation improved the
      30-day survival from 0 to 100%. CONCLUSION: These results show the pre-clinical
      utility of S. typhimurium as a TRAIL expression vector that effectively reduces
      tumour growth and extends host survival.

PMID- 19861962
TI  - Assessment of breast cancer opportunistic screening by clinical-pathological
      indicators: a population-based study.
AB  - BACKGROUND: Although some clinical-pathological features of breast cancers, such
      as the incidence of ductal cancer in situ (DCIS) and the diameter of invasive
      tumours, are sensitive indicators of early detection, comprehensive population
      based studies of opportunistic screening are needed. METHODS: Cases of DCIS or
      invasive breast cancer diagnosed in 1996-2007 were identified from the Ticino
      Cancer Registry (south of Switzerland). Time trends of age-adjusted incidence and
      mortality, as well as main clinical-pathological features, such as tumour
      diameter, AJCC stage and histological grade, were analysed. RESULTS: A total of
      3047 incident cases of female breast cancer were identified. The proportion of
      DCIS with respect to invasive cases increased from 5.8% in the period 1996-2001
      to 6.4% in the period 2002-2007. The median tumour size of invasive cancers
      decreased from 20 mm in 1996-2001 to 18 mm in 2002-2007 (P<0.0001). An increase
      in well/moderately differentiated invasive tumours, from 67% in the period 1996
      2001 to 73% in 2002-2007 (P<0.001), was detected and resulted in an Annual
      Percentage Change of incidence of 2.8 (95% confidence interval: 1.3; 4.3).
      CONCLUSION: An opportunistic screening strategy can lead to an improvement of
      prognostic features at diagnosis, but these features are still less favourable
      than those achieved by organised screening programmes.

PMID- 19861963
TI  - Activation and clinical significance of the unfolded protein response in breast
      cancer.
AB  - INTRODUCTION: The tumour microenvironment is hypoglycaemic, hypoxic and acidotic.
      This activates a stress signalling pathway: the unfolded protein response (UPR).
      The UPR is cytoprotective if the stressor is mild, but may initiate apoptosis if
      severe.Activation of the UPR in breast carcinoma is induced by microenvironmental
      stress such as glucose and oxygen deprivation, but may also be linked to
      oestrogen stimulation. It may be clinically significant as it may alter
      chemosensitivity to doxorubicin. METHODS: 395 human breast adenocarcinomas were
      immunohistochemically stained for UPR activation markers (glucose-regulated
      protein (GRP-78 and XBP-1). A model of UPR activation in vitro by glucose
      deprivation of T47D breast cancer cells was developed to determine how the UPR
      affects cellular sensitivity to doxorubicin and 5-fluorouracil. Cytotoxicity was
      assessed using a colorimetric cytotoxicity assay (MTT). The effect of oestrogen
      stimulation and tamoxifen exposure on UPR activation by T47D cells was determined
      by western blotting measurement of the key UPR protein, GRP-78. RESULTS:
      Expression of GRP78 and XBP-1 was demonstrated in 76% and 90% of the breast
      cancers, respectively, and correlated with oestrogen receptor positivity (P=0.045
      and 0.017, respectively). In vitro UPR activation induced resistance to both
      doxorubicin and 5-flurouracil, (P<0.05). Oestrogen stimulation induced GRP78 and
      XBP1 over-expression on western blotting. Tamoxifen did not block this response
      and may induce UPR activation in its own right. CONCLUSIONS: The UPR is activated
      in the majority of breast cancers and confers resistance to chemotherapy. In
      vitro oestrogen stimulates UPR induction. UPR activation may contribute to breast
      cancer chemoresistance and interact with oestrogen response elements.

PMID- 19861964
TI  - Detection of BRAF mutations in the tumour and serum of patients enrolled in the
      AZD6244 (ARRY-142886) advanced melanoma phase II study.
AB  - BACKGROUND: This study investigated the potential clinical utility of circulating
      free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into
      a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with
      advanced melanoma. METHODS: BRAF mutations were detected using Amplification
      Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed
      in serum-derived cfDNA from 126 patients enrolled into the study and from 94
      matched tumour samples. RESULTS: Of 94 tumour samples, 45 (47.9%) were found to
      be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126
      (26.2%) samples, including in five samples for which tumour data were
      unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three
      cases in which the tumour was negative, cfDNA was BRAF+. Progression-free
      survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly
      different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating
      that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage
      III/IV advanced melanoma. CONCLUSIONS: These data demonstrate the feasibility of
      BRAF mutation detection in cfDNA of patients with advanced melanoma. Future
      studies should aim to incorporate BRAF mutation testing in cfDNA to further
      validate this biomarker for patient selection.

PMID- 19861966
TI  - Inside lab invest.

PMID- 19861965
TI  - A prospective study of lifetime physical activity and prostate cancer incidence
      and mortality.
AB  - BACKGROUND: The possible benefit of lifetime physical activity (PA) in reducing
      prostate cancer incidence and mortality is unclear. METHODS: A prospective cohort
      of 45,887 men aged 45-79 years was followed up from January 1998 to December 2007
      for prostate cancer incidence (n=2735) and to December 2006 for its subtypes and
      for fatal (n=190) prostate cancer. RESULTS: We observed an inverse association
      between lifetime (average of age 30 and 50 years, and baseline age) total PA
      levels and prostate cancer risk. Multivariate-adjusted incidence in the top
      quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)=2
      27%) compared with that in the bottom quartile. We also observed an inverse
      association between average lifetime work or occupational activity and walking or
      bicycling duration and prostate cancer risk. Compared with men who mostly sit
      during their main work or occupation, men who sit half of the time experienced a
      20% lower risk (95% CI=7-31%). The rate ratio linearly decreased by 7% (95% CI=1
      12%) for total, 8% (95% CI=0-16%) for localised and 12% (95% CI=2-20%) for
      advanced prostate cancer for every 30 min per day increment of lifetime walking
      or bicycling in the range of 30 to 120 min per day. CONCLUSIONS: Our results
      suggest that not sitting for most of the time during work or occupational
      activity and walking or bicycling more than 30 min per day during adult life is
      associated with reduced incidence of prostate cancer.

PMID- 19861967
TI  - Connecting the dots: obesity, fatty acids and cancer.
AB  - Obesity is becoming recognized as a common co-morbidity with several disease
      states including cancer. There is tremendous interest to more fully understand
      the mechanistic connections between obesity and cancer. This commentary
      highlights the report by Byon et al in this issue of Laboratory Investigation. It
      provides an interpretation of their results in the context of other disease
      states involving obesity and its sequelae of excess fatty acids and increased
      plasminogen activator inhibitor-1 (PAI-1) concentrations. This includes obesity
      related conditions, in particular metabolic syndrome, and its subphenotypes such
      as insulin resistance, and increased risk of myocardial infarction. The potential
      mechanistic tie-ins of obesity, elevated concentrations of fatty acids, as well
      as elevated PAI-1 levels with cancer and its risk for aggressiveness are
      discussed.

PMID- 19861968
TI  - Reducing primary cesarean delivery: can we prevent current and future morbidity
      and mortality?

PMID- 19861969
TI  - Hippocratic ideal, Faustian bargain and Damocles' sword: erosion of patient
      autonomy in obstetrics.
AB  - Respect for patient autonomy remains a foundational principle guiding the ethical
      practice of medicine-a mission first articulated by Hippocrates. Damocles,
      another figure from ancient Greece, provides a useful parable for describing
      performance under distress: Damocles loses his desire for opulence and power when
      he notices a sword dangling precariously above his head. Contemporary
      obstetricians deciding whether to forestall or impose major abdominal surgery on
      parturients entrusted to their care struggle valiantly in the chasm dividing
      Hippocratic idealism from the economic realism driven by the medicolegal sword of
      Damocles. Given the inherent risk of unforeseeable and unsalvageable fetal
      catastrophe during labor and vaginal delivery, and the often unsubstantiated, yet
      automatic, allegation of negligence that follows a labor-associated adversity,
      obstetricians-and their liability insurance carriers-have recalibrated obstetric
      practice in alignment with the increasingly risk-averse preferences of most
      patients. Indeed, less intrapartum risk for patients and less corresponding
      medicolegal exposure for obstetricians help explain the rising cesarean delivery
      rate and, more importantly, the steady disappearance of higher-risk interventions
      such as vaginal birth after cesarean (VBAC). Is this increasing reluctance to
      offer VBAC supervision ethically defensible? This paper argues that it is.
      Fiduciary professionalism mandates physician self-sacrifice, not self
      destruction; a VBAC gone awry without negligence or substandard care may,
      nevertheless, render future affordable liability coverage unattainable. Yet, the
      unavailability of VBAC infringes on the autonomy of women who want to assume the
      intrapartum risks of a VBAC in lieu of a repeat cesarean delivery. The proposed
      solution is the regionalization of VBAC care provision in designated medical
      centers and/or the implementation of binding arbitration in an ethical trade-off
      to enhance patient autonomy regarding the preferred mode of delivery despite
      parallel constraint on legal options.

PMID- 19861971
TI  - Colorectal tubular enteric duplication.

PMID- 19861970
TI  - A premature infant with fetal myocardial and abdominal calcifications and factor
      V Leiden homozygosity.
AB  - We present a premature male neonate with confirmed factor V Leiden deficiency
      diagnosed prenatally with cardiac and abdominal calcifications. Our patient's
      findings suggest that clinicians consider thromboembolic conditions when multiple
      fetal calcifications are visualized.

PMID- 19861972
TI  - Iba1(+)/NG2(+) macrophage-like cells expressing a variety of neuroprotective
      factors ameliorate ischemic damage of the brain.
AB  - In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a
      large ischemic lesion is formed where macrophage-like cells massively accumulate,
      many of which express a macrophage marker, Iba1, and an oligodendrocyte
      progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore,
      the cells were termed BINCs (Brain Iba1(+)/NG2(+) Cells). A bone marrow
      transplantation experiment using green-fluorescent protein-transgenic rats showed
      that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2
      days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr,
      causing enlargement of necrotic volumes and frequent death of the rats. When
      isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume
      of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs
      expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and
      VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level.
      Immunohistochemical staining showed that IGF-1-expressing BINCs were found not
      only in rat but also human ischemic brain lesions. These results suggest that
      bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at
      least in part, through secretion of neuroprotective factors.

PMID- 19861973
TI  - Estrogen-receptor-mediated protection of cerebral endothelial cell viability and
      mitochondrial function after ischemic insult in vitro.
AB  - Protective effects of estrogen against experimental stroke and neuronal ischemic
      insult are well-documented, but it is not known whether estrogen prevents
      ischemic injury to brain endothelium, a key component of the neurovascular unit.
      Increasing evidence indicates that estrogen exerts protective effects through
      mitochondrial mechanisms. We previously found 17beta-estradiol (E2) to improve
      mitochondrial efficiency and reduce mitochondrial superoxide in brain blood
      vessels and endothelial cells. Thus we hypothesized E2 will preserve
      mitochondrial function and protect brain endothelial cells against ischemic
      damage. To test this, an in vitro ischemic model, oxygen-glucose deprivation
      (OGD)/reperfusion, was applied to immortalized mouse brain endothelial cells
      (bEnd.3). OGD/reperfusion-induced cell death was prevented by long-term (24, 48
      h), but not short-term (0.5, 12 h), pretreatment with 10 nmol/L E2. Protective
      effects of E2 on endothelial cell viability were mimicked by an estrogen-receptor
      (ER) agonist selective for ERalpha (PPT), but not by one selective for ERbeta
      (DPN). In addition, E2 significantly decreased mitochondrial superoxide and
      preserved mitochondrial membrane potential and ATP levels in early stages of
      OGD/reperfusion. All of the E2 effects were blocked by the ER antagonist, ICI
      182,780. These findings indicate that E2 can preserve endothelial mitochondrial
      function and provide protection against ischemic injury through ER-mediated
      mechanisms.

PMID- 19861974
TI  - The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to
      cerebral hypoxia-ischemia in the diabetic ob/ob mouse.
AB  - Diabetes is an increased risk factor for stroke and results in increased brain
      damage in experimental animals and humans. The precise mechanisms are unclear,
      but our earlier studies in the db/db mice suggested that the cerebral
      inflammatory response initiating recovery was both delayed and diminished in the
      diabetic mice compared with the nondiabetic db/+ mice. In this study, we
      investigated the actions of the peroxisome proliferator-activated receptor (PPAR)
      gamma agonist darglitazone in treating diabetes and promoting recovery after a
      hypoxic-ischemic (H/I) insult in the diabetic ob/ob mouse. Male ob/+ and ob/ob
      mice received darglitazone (1 mg/kg) for 7 days before induction of H/I.
      Darglitazone restored euglycemia and normalized elevated corticosterone,
      triglycerides, and very-low-density lipoprotein levels. Darglitazone dramatically
      reduced the infarct size in the ob/ob mice at 24 h of recovery compared with the
      untreated group (30+/-13% to 3.3+/-1.6%, n=6 to 8) but did not show any
      significant effect in the ob/+ mice. Microglial and astrocytic activation
      monitored by cytokine expression (interleukin-1beta and tumor necrosis factor
      alpha) and in situ hybridization studies (bfl1 and glial fibrillary acidic
      protein) suggest a biphasic inflammatory response, with darglitazone restoring
      the compromised proinflammatory response(s) in the diabetic mouse at 4 h but
      suppressing subsequent inflammatory responses at 8 and 24 h in both control and
      diabetic mice.

PMID- 19861975
TI  - Stimulatory effects of thyroid hormone on brain angiogenesis in vivo and in
      vitro.
AB  - Thyroid hormone is critical for the proper development of the central nervous
      system. However, the specific role of thyroid hormone on brain angiogenesis
      remains poorly understood. Treatment of rats from birth to postnatal day 21 (P21)
      with propylthiouracil (PTU), a reversible blocker of triiodothyronine (T3)
      synthesis, resulted in decreased brain angiogenesis, as indicated by reduced
      complexity and density of microvessels. However, when PTU was withdrawn at P22,
      these parameters were fully recovered by P90. These changes were paralleled by an
      altered expression of vascular endothelial growth factor A (Vegfa) and basic
      fibroblast growth factor (Fgf2). Physiologic concentrations of T3 and thyroxine
      (T4) stimulated proliferation and tubulogenesis of rat brain-derived endothelial
      (RBE4) cells in vitro. Protein and mRNA levels of VEGF-A and FGF-2 increased
      after T3 stimulation of RBE4 cells. The thyroid hormone receptor blocker NH-3
      abolished T3-induced Fgf2 and Vegfa upregulation, indicating a receptor-mediated
      effect. Thyroid hormone inhibited the apoptosis in RBE4 cells and altered mRNA
      levels of apoptosis-related genes, namely Bcl2 and Bad. The present results show
      that thyroid hormone has a substantial impact on vasculature development in the
      brain. Pathologically altered vascularization could, therefore, be a contributing
      factor to the neurologic deficits induced by thyroid hormone deficiency.

PMID- 19861976
TI  - Prevention of hypoglycemia-induced neuronal death by hypothermia.
AB  - Hypothermia reduces neuronal damage after cerebral ischemia and traumatic brain
      injury, while hyperthermia exacerbates damage from these insults. Previously we
      have shown that temperature-dependent modulation of excitotoxic neuronal death is
      mediated in part by temperature-dependent changes in the synaptic
      release/translocation of Zn(2+). In this study, we hypothesize that brain
      temperature also affects hypoglycemia-induced neuronal death by modulation of
      vesicular Zn(2+) release from presynaptic terminals. To test our hypothesis, we
      used a rat model of insulin-induced hypoglycemia. Here we found that hypoglycemia
      induced neuronal injury was significantly affected by brain temperature, that is,
      hypothermia inhibited while hyperthermia aggravated neuronal death. To
      investigate the mechanism of temperature-dependent neuronal death after
      hypoglycemia, we measured zinc release/translocation, reactive oxygen species
      (ROS) production, and microglia activation. Here we found that hypoglycemia
      induced Zn(2+) release/translocation, ROS production, and microglia activation
      were inhibited by hypothermia but aggravated by hyperthermia. Even when the
      insult was accompanied by hyperthermic conditions, zinc chelation inhibited ROS
      production and microglia activation. Zinc chelation during hyperthermia reduced
      neuronal death, superoxide production, and microglia activation, which was
      comparable to the protective effects of hypothermia. We conclude that neuronal
      death after hypoglycemia is temperature-dependent and is mediated by increased
      Zn(2+) release, superoxide production, and microglia activation.

PMID- 19861977
TI  - Guidelines for preventing infectious complications among hematopoietic cell
      transplant recipients: a global perspective. Preface.

PMID- 19861978
TI  - Background to hematopoietic cell transplantation, including post transplant
      immune recovery.

PMID- 19861979
TI  - Hematopoietic cell graft safety.

PMID- 19861980
TI  - Bacterial infection prevention after hematopoietic cell transplantation.

PMID- 19861981
TI  - Viral disease prevention after hematopoietic cell transplantation.

PMID- 19861982
TI  - Fungal infection prevention after hematopoietic cell transplantation.

PMID- 19861983
TI  - Regionally limited or rare infections: prevention after hematopoietic cell
      transplantation.

PMID- 19861984
TI  - Infection prevention and control in health-care facilities in which hematopoietic
      cell transplant recipients are treated.

PMID- 19861985
TI  - Safe living after hematopoietic cell transplantation.

PMID- 19861986
TI  - Vaccination of hematopoietic cell transplant recipients.

PMID- 19861989
TI  - The NIH entitlement program.

PMID- 19861990
TI  - Imaging: PET-CT imaging in non-small-cell lung cancer.

PMID- 19861991
TI  - Chemotherapy: Adding oxaliplatin to the equation.

PMID- 19861992
TI  - Hematology: The case against rituximab maintenance.

PMID- 19861993
TI  - Hematology: Follicular lymphoma: maintenance therapy is (often) indicated.

PMID- 19861994
TI  - Refractory neuroendocrine tumor-response to liposomal doxorubicin and
      capecitabine.
AB  - BACKGROUND: A 61-year-old patient with no relevant medical or family history
      presented with a 2 month history of refractory dry cough that led to the
      diagnosis of typical carcinoid tumor of the lung metastatic to the mediastinal
      lymph nodes and liver. She initially received a long-acting somatostatin analog
      (octreotide) and chemotherapy with cisplatin and etoposide, which was
      ineffective. INVESTIGATIONS: Physical examination, laboratory test, chromogranin
      A test, CT scan, (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide
      scan, (18)F-FDG-PET scan, fine-needle and tissue core liver biopsies. DIAGNOSIS:
      Pulmonary spindle-cell carcinoid tumor with metastases to mediastinal lymph nodes
      and liver. MANAGEMENT: Systemic treatment with oral capecitabine (1,500 mg/m(2)
      daily from day 1 to day 21) and intravenous liposomal doxorubicin (10 mg/m(2) on
      days 1, 8 and 15), both repeated every 4 weeks, administered concomitantly with
      long-acting octreotide 30 mg every 3 weeks. The patient achieved a significant
      and long-lasting response with the combination of capecitabine and liposomal
      doxorubicin. She reported no severe adverse effects.

PMID- 19861995
TI  - Robotic-assisted laparoscopic prostatectomy.
AB  - Prostate cancer remains a significant health problem worldwide and is the second
      highest cause of cancer-related death in men. While there is uncertainty over
      which men will benefit from radical treatment, considerable efforts are being
      made to reduce treatment related side-effects and in optimising outcomes. This
      article reviews the development and introduction of robotic-assisted laparoscopic
      radical prostatectomy (RALP), the results to date, and the possible future
      directions of RALP.

PMID- 19861996
TI  - Mechanisms of HTLV-1 persistence and transformation.
AB  - Adult T-cell leukaemia (ATL) is caused by the human T-cell lymphotropic virus
      type 1 (HTLV-1). HTLV-1 has elaborated strategies to persist and replicate in the
      presence of a strong immune response. In this review, we summarise these
      mechanisms and their contribution to T-cell transformation and ATL development.

PMID- 19861997
TI  - A trial of consent procedures for future research with clinically derived
      biological samples.
AB  - BACKGROUND: The aims of this study were to determine which consent procedure
      patients prefer for use of stored tissue for research purposes and what the
      effects of consent procedures on actual consenting behaviour are. METHODS: We
      offered 264 cancer patients three different consent procedures: 'one-time general
      consent' (asked written informed consent), 'opt-out plus' (had the opportunity to
      opt out by a form), or the standard hospital procedure (control group). The two
      intervention groups received a specific leaflet about research with residual
      tissue and verbal information. The control group only received a general hospital
      leaflet including opt-out information, which is the procedure currently in use.
      Subsequently, all patients received a questionnaire to examine their preferences
      for consent procedures. RESULTS: In all, 99% of patients consented to research
      with their residual tissue. In the 'one-time consent' group 85% sent back their
      consent form. Patients preferred 'opt-out plus' (43%) above 'one-time consent'
      (34%) or 'opt-out' (16%), whereas 8% indicated that they did not need to receive
      information about research with residual tissues or be given the opportunity to
      make a choice. CONCLUSIONS: The 'opt-out plus' procedure, which places fewer
      demands on administrative resources than 'one-time consent', can also address the
      information needs of patients.

PMID- 19861998
TI  - Intraepithelial CD8-positive T lymphocytes predict survival for patients with
      serous stage III ovarian carcinomas: relevance of clonal selection of T
      lymphocytes.
AB  - BACKGROUND: The aim of this study was to investigate the prognostic effect of
      tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to
      determine TIL clonality and to correlate this to Her2/neu expression. METHODS:
      Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-,
      CD3-, CD4- and CD8-positive lymphocytes (n=100), and for Her2/neu-positive tumour
      cells (n=55/100) by immunohistochemistry. Clonality analysis was carried out by T
      cell receptor gamma (TCRgamma) gene rearrangements (n=93/100). Statistical
      analyses included experimental and clinico-pathological variables, as well as
      disease-free (DFS) and overall (OS) survival. RESULTS: CD20-positive B
      lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3
      positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian
      carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with
      improved DFS in optimally debulked patients (P=0.0402). Intraepithelial CD8
      positive T lymphocytes were correlated with improved OS in all optimally debulked
      patients (P=0.0201) and in those undergoing paclitaxel/carboplatin therapy
      (P=0.0092). Finally, rarified and clonal TCRgamma gene rearrangements were
      detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively.
      This was marginally associated with improved DFS (P=0.0873). Despite a
      significant correlation of HER2/neu status and intraepithelial CD8-positive
      lymphocytes (P=0.0264), this was non-directional (R=-0.257; P=0.0626).
      CONCLUSION: Improved survival of ovarian cancer patients is related to the
      infiltration, clonal selection and intraepithelial persistence of T lymphocytes.

PMID- 19861999
TI  - Radiological staging in breast cancer: which asymptomatic patients to image and
      how.
AB  - BACKGROUND: Approximately 4% of patients diagnosed with early breast cancer have
      occult metastases at presentation. Current national and international guidelines
      lack consensus on whom to image and how. METHODS: We assessed practice in
      baseline radiological staging against local guidelines for asymptomatic newly
      diagnosed breast cancer patients presenting to the Cambridge Breast Unit over a 9
      year period. RESULTS: A total of 2612 patients were eligible for analysis; 91.7%
      were appropriately investigated. However in the subset of lymph node negative
      stage II patients, only 269 out of 354 (76.0%) investigations were appropriate.
      No patients with stage 0 or I disease had metastases; only two patients (0.3%)
      with stage II and < or =3 positive lymph nodes had metastases. Conversely, 2.2,
      2.6 and 3.8% of these groups had false-positive results. The incidence of occult
      metastases increased by stage, being present in 6, 13.9 and 57% of patients with
      stage II (> or =4 positive lymph nodes), III and IV disease, respectively.
      CONCLUSION: These results prompted us to propose new local guidelines for staging
      asymptomatic breast cancer patients: only clinical stage III or IV patients
      require baseline investigation. The high specificity and convenience of computed
      tomography (chest, abdomen and pelvis) led us to recommend this as the
      investigation of choice in breast cancer patients requiring radiological staging.

PMID- 19862000
TI  - Chemotherapy-induced neutropenia as a prognostic factor in advanced non-small
      cell lung cancer: results from Japan Multinational Trial Organization LC00-03.
AB  - BACKGROUND: Neutropenia is a common adverse reaction of chemotherapy. We assessed
      whether chemotherapy-induced neutropenia could be a predictor of survival for
      patients with non-small-cell lung cancer (NSCLC). METHODS: A total of 387
      chemotherapy-naive patients who received chemotherapy (vinorelbine and
      gemcitabine followed by docetaxel, or paclitaxel and carboplatin) in a randomised
      controlled trial were evaluated. The proportional-hazards regression model was
      used to examine the effects of chemotherapy-induced neutropenia and tumour
      response on overall survival. Landmark analysis was used to lessen the bias of
      more severe neutropenia resulting from more treatment cycles allowed by longer
      survival, whereby patients who died within 126 days of starting chemotherapy were
      excluded. RESULTS: The adjusted hazard ratios for patients with grade-1 to 2
      neutropenia or grade-3 to 4 neutropenia compared with no neutropenia were 0.59
      (95% confidence interval (CI), 0.36-0.97) and 0.71 (95% CI, 0.49-1.03),
      respectively. The hazard ratios did not differ significantly between the patients
      who developed neutropenia with stable disease (SD), and those who lacked
      neutropenia with partial response (PR). CONCLUSION: Chemotherapy-induced
      neutropenia is a predictor of better survival for patients with advanced NSCLC.
      Prospective randomised trials of early-dose increases guided by chemotherapy
      induced toxicities are warranted.

PMID- 19862001
TI  - Alcohol intake and risk of thyroid cancer in the NIH-AARP Diet and Health Study.
AB  - BACKGROUND: Certain studies suggest that alcohol may reduce the risk of thyroid
      cancer in women, but the effect in men remains unclear. METHODS: We analysed the
      association between alcohol and thyroid cancer in a large (n=490 159) prospective
      NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes.
      RESULTS: Over 7.5 years of follow-up (median), 170 men and 200 women developed
      thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol
      consumption (> or =2 drinks per day vs none, relative risk=0.57, 95% CI 0.36
      0.89, P-trend=0.01). CONCLUSIONS: These results suggest a potential protective
      role for alcohol consumption in thyroid cancer.

PMID- 19862002
TI  - Human papillomavirus infection in Beijing, People's Republic of China: a
      population-based study.
AB  - BACKGROUND: No recent data exist on human papillomavirus (HPV) infection in
      Beijing, People's Republic of China. MATERIALS AND METHOD: We interviewed and
      examined a representative, randomly selected sample of 5552 sexually active women
      aged 25-54 years. Cervical cell samples were analysed for HPV DNA by a MY09/11
      based PCR assay. RESULTS: Human papillomavirus prevalence was 6.7% overall and
      4.8% among women without cervical abnormalities. Of the 21 subtypes identified,
      HPV16 was the commonest type (2.6% overall; 39.1% of HPV-positive women),
      followed by HPV 58 (1.0%), 33 (0.8%), 43 (0.7%) and 56 (0.7%). High-risk HPV
      types predominated in all age groups. Human papillomavirus prevalence was highest
      in young to middle-aged women. Marital status, number of husband's sexual
      partners, age at sexual debut and nulligravidity were all associated with being
      HPV positive. CONCLUSIONS: In our survey, HPV 16, HPV 58 and HPV 33 were the most
      prevalent HPV types in Beijing, indicating the potential for the prophylactic HPV
      16/18 vaccine in China.

PMID- 19862004
TI  - Data divorce.

PMID- 19862003
TI  - Pickled vegetables and the risk of oesophageal cancer: a meta-analysis.
AB  - BACKGROUND: Ecological and experimental studies have suggested a relationship
      between Asian pickled vegetable consumption and oesophageal squamous cell
      carcinoma (OSCC), but the results of epidemiological studies investigating the
      association have been inconsistent. We conducted a meta-analysis of observational
      studies of this association to evaluate the existing evidence. METHODS: We
      searched the PubMed, ISI-Web of Science, J-EAST, IndMed, Vip Chinese Periodical,
      and China National Knowledge Infrastructure databases for all studies published
      in English or Chinese languages. Pooled results for all studies combined and for
      several study subgroups were computed. RESULTS: A total of 34 studies were
      included in this analysis. The overall random effects odds ratio (OR) and 95%
      confidence interval (CI) for pickled vegetable consumption was 2.08 (1.66-2.60),
      but the results were heterogeneous across studies. After excluding the three most
      influential studies, the respective numbers were 2.32 (1.92-2.81). Similar to the
      overall association, the majority of subgroup analyses showed a statistically
      significant association between consuming pickled vegetables and OSCC risk. There
      were only three prospective studies. CONCLUSION: Our results suggest a potential
      two-fold increased risk of oesophageal cancer associated with the intake of
      pickled vegetables. However, because the majority of data was from retrospective
      studies and there was a high heterogeneity in the results, further well-designed
      prospective studies are warranted.

PMID- 19862006
TI  - Genes determining blood cell traits.

PMID- 19862007
TI  - Not so lost in the genetic crowd.

PMID- 19862008
TI  - DNA methylation is a guardian of stem cell self-renewal and multipotency.

PMID- 19862011
TI  - An insect-endosymbiont conundrum.

PMID- 19862012
TI  - Polarization chaos in an optically pumped laser.
AB  - We study the steady-state and dynamic behavior of an optically pumped J = 0 ? J =
      1 ? J = 0 laser operating with an isotropic ring cavity and an axial magnetic
      field. The gain anisotropy induced by a linearly polarized pump-laser f ield
      leads, in the steady state, to locking of the two circularly polarized components
      of the laser field, which acquires a linear polarization parallel to that of the
      pump field. In the presence of laser intensity instabilities, however, locking
      does not occur, and polarization instabilities appear. For the f irst time to our
      knowledge, polarization chaos has been found in a laser system.

PMID- 19862013
TI  - Depolarization of light backscattered by randomly oriented nonspherical
      particles.
AB  - We derive theoretically and validate numerically general relationships for the
      elements of the backscattering matrix and for the linear, delta(L), and circular,
      delta(C), backscattering depolarization ratios for nonspherical particles in
      random orientation. For the practically important case of randomly oriented
      particles with a plane of symmetry or particles and their mirror particles
      occurring in equal numbers and in random orientation, delta(C) = 2delta(L)/(1 -
      delta(L)). Extensive T-matrix computations for randomly oriented spheroids
      demonstrate that, although both delta(L) and delta(C) are indicators of particle
      nonsphericity, they cannot be considered a universal measure of the departure of
      particle shape from that of a sphere and have no simple dependence on particle
      size and refractive index.

PMID- 19862014
TI  - Effect of the stratosphere on star image motion.
AB  - The joint effect of non-Kolmogorov stratospheric and Kolmogorov tropospheric
      turbulence on star image motion is studied, and the theoretical predictions are
      compared with measured data. It is shown that for a large telescope the
      stratospheric effect has been dramatically underestimated. The techniques that
      permitted us to single out the contribution of the stratosphere to star image
      motion and to exclude the effect of uncontrolled telescope motion on the measured
      data are described.

PMID- 19862015
TI  - Optoelectronic hit/miss transform for screening cervical smear slides.
AB  - An optoelectronic morphological processor for detecting regions of interest
      (abnormal cells) on a cervical smear slide using the hit/miss transform is
      presented. Computer simulation of the algorithm tested on 184 Papsmear images
      provided 95% detection and 5% false alarm. An optoelectronic implementation of
      the hit /miss transform is presented, along with preliminary experimental
      results.

PMID- 19862010
TI  - Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
AB  - Measurements of erythrocytes within the blood are important clinical traits and
      can indicate various hematological disorders. We report here genome-wide
      association studies (GWAS) for six erythrocyte traits, including hemoglobin
      concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean
      corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC)
      and red blood cell count (RBC). We performed an initial GWAS in cohorts of the
      CHARGE Consortium totaling 24,167 individuals of European ancestry and
      replication in additional independent cohorts of the HaemGen Consortium totaling
      9,456 individuals. We identified 23 loci significantly associated with these
      traits in a meta-analysis of the discovery and replication cohorts (combined P
      values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci
      previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as
      well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has
      identified new determinants of erythrocyte traits, offering insight into common
      variants underlying variation in erythrocyte measures.

PMID- 19862016
TI  - Periodic amplification and conjugation of optical solitons.
AB  - Nondegenerate optical parametric amplifiers can be used to simultaneously phase
      conjugate and amplify a pulse in a nonlinear optical fiber. The gain in the
      amplifiers compensates the linear loss in the fiber, while the phase conjugation
      effectively neutralizes second-order dispersion, self-phase modulation, the Raman
      self-frequency shift, and Gordon-Haus jitter. If the remaining third-order and
      nonlinear dispersions balance, solitonlike pulses are able to propagate with
      subpicosecond pulse widths.

PMID- 19862018
TI  - All-fiber polarizer based on a null taper coupler.
AB  - An entirely new type of single-mode all-fiber polarizer is reported. The
      polarizer is based on a narrow circularly fused null taper coupler, which was
      twisted through 45 degrees after being made. The polarizing effect is due to the
      excitation of hybrid second modes in the coupler waist. An extinction ratio of 15
      dB and an insertion loss of 0.2 dB have been obtained, with scope for further
      improvement.

PMID- 19862017
TI  - Cubic optical nonlinearity of free electrons in bulk gold.
AB  - A fast (Tau(response) <90 fs) free-electron spin-f lipping frequency-degenerate
      nonlinearity with a signif icant value of|chi((3))(xxyy)(omega,omega,omega,
      omega)chi((3))(xxyy)(omega,omega,omega,-omega)|~10(-)(8)esu has been observed in
      bulk gold at 1260 nm by use of a new pump-probe polarization-sensitive technique.

PMID- 19862019
TI  - Thermal annealing of K(+)-Na(+) ion-exchanged waveguides.
AB  - The process of thermal annealing of K(+)(-)Na(+) ion-exchanged waveguides in soda
      lime glass is characterized and compared with a simple theoretical model. The
      discrepancies between theory and experiments in the case of initially thick
      guides disappear if the existence of a stress-induced contribution to the
      refractive index is assumed that is not proportional to the concentration of the
      doping ions. The results obtained for initially thin guides are exploited for the
      design of annealed single-mode channel waveguides: 0.4-dB coupling losses with
      commercial single-mode fibers at lambda = 1.321 microm were measured.

PMID- 19862020
TI  - Antiresonant reflecting optical waveguides formed from solgel films.
AB  - An investigation of the losses exhibited by antiresonant ref lecting optical
      waveguides (ARROW's) formed from solution-deposited solgel films is reported.
      Solgel layers formed from methyltrimethoxysilane (MTMS) and titanium (iv)
      propoxide were used to fabricate a simple ARROW structure. Using a combination of
      MTMS and titanium (iv) propoxide produced good optical quality layers with
      thicknesses ranging from 1 to 20 microm. Losses as low as 2 dB/cm were measured
      experimentally for these ARROW devices.

PMID- 19862021
TI  - Improvement of the beam quality of a gasdynamically cooled CO laser with an
      unstable resonator by use of a cylindrical mirror.
AB  - The beam quality of a gasdynamically cooled CO laser with an unstable resonator
      (M = 1.7) has been improved by use of an extracavity cylindrical mirror. This
      mirror corrects the phase distortion resulting from the supersonic f low. A 4.5
      kW laser beam with a total divergence of 1.4 mrad is obtained with an efficiency
      of 9% and a Strehl ratio of 0.4. A strong degradation of the beam quality has
      been observed outside the resonator owing to water-vapor absorption. The use of
      dry air in the beam-guiding system signif icantly reduces this effect of thermal
      blooming.

PMID- 19862023
TI  - Lasing at 7.9 nm in nickellike neodymium.
AB  - Using a series of 150-ps pulses from the Nova laser to illuminate neodymium slab
      targets, we observe a 38-psduration lasing pulse at 7.906 nm in nickellike
      neodymium on the J = 0 ? 1, 4d ? 4p transition. To overcome the low gain in this
      system, we used a traveling-wave geometry in conjunction with two slab targets
      that were coupled lengthwise to increase the effective length and whose surfaces
      were curved to compensate partially for refraction effects.

PMID- 19862022
TI  - Stable high-repetition-rate single-frequency Q-switched operation by feedback
      suppression of relaxation oscillation.
AB  - Stable single-frequency operation of a Q-switched laser requires the initial
      establishment of a stable prelase, free from relaxation oscillation. Relying on
      natural decay of oscillation limits repetition rates and hence average power.
      Using feedback suppression of relaxation oscillation, a Q-switched Nd:YAG laser
      has operated reliably on a single frequency at repetition rates up to 25 kHz,
      with 88% of available cw power extracted.

PMID- 19862024
TI  - Diode-pumped single-frequency Nd:YVO(4) laser with a set of coupled resonators.
AB  - 350 mW of single-frequency power from a diode-pumped solid-state Nd:YVO(4) laser
      has been obtained from a coupled resonator design without any intracavity
      elements. Single-frequency operation was obtained by use of a very short laser
      rod and a coupled resonator design. The two coupled resonators were formed by the
      two faces of a very short Nd:YVO(4) laser crystal and an output coupling mirror.
      The interaction of the two coupled cavities caused a modification of the
      eigenmodes supporting laser action in a single longitudinal mode. This design,
      which is extremely simple, represents a cost-eff icient way of obtaining single
      frequency output.

PMID- 19862025
TI  - Short-wavelength far-infrared laser cavity yielding new lines in methanol.
AB  - We report 16 new laser lines generated in a short-wavelength far-infrared Fabry
      Perot laser cavity. The CO(2) pump laser is coupled into the far-infrared laser
      outside the far-infrared laser mode, and the cavity uses a 45 degrees adjustable
      output coupling mirror; this combination results in a low-loss Fabry-Perot cavity
      for wavelengths below 150 microm. The new lines are of medium and strong
      intensity and have wavelengths in the region 26.2-125.7 microm.

PMID- 19862026
TI  - Near-transform-limited visible and near-IR femtosecond pulses from optical
      parametric amplification using Type II beta-barium borate.
AB  - Type II phase-matched beta-barium borate is used in the f irst stage of amplif
      ication of a white-light continuum in a two-stage optical parametric amplifier
      pumped by the second harmonic of a regeneratively amplified Ti:sapphire laser
      system operating at 824 nm. Near-transform-limited sub-190-fs pulses with
      microjoule energies are achieved in the signal branch, which is tunable from 475
      nm to degeneracy. This system effectively bridges the wavelength gap between the
      fundamental and the second harmonic of amplified Ti:sapphire laser systems.

PMID- 19862028
TI  - Single-event observation of high-speed signals by interferometric spectral
      detection with a synthesized local oscillator.
AB  - The single-shot detection of a high-speed 4-pJ optical signal is confirmed for
      the first time, to the author's knowledge, by use of a previously proposed
      interferometric spectral detection technique.

PMID- 19862027
TI  - Sub-20-fs, kilohertz-repetition-rate Ti:sapphire amplifier.
AB  - A simple four-pass Ti:sapphire amplifier is seeded by sub-10-fs pulses generated
      from a mirror-dispersion-controlled Ti:sapphire laser. Pulses of 17-18-fs
      duration with energies up to 50 and 100 microJ have been produced at repetition
      rates of 2 and 1 kHz, respectively. Because of the absence of a pulse stretcher,
      this performance is achieved from an extremely compact system.

PMID- 19862029
TI  - Generation of high-power subpicosecond pulses at 155 nm.
AB  - Subpicosecond vacuum-ultraviolet radiation at 155 nm with pulse energies above
      0.2 mJ has been obtained by near-resonant four-wave difference-frequency mixing
      in a Xe gas jet. Laser fields for the mixing process have been generated by a
      short-pulse KrF dye excimer laser system and a Raman converter. The process
      permits tuning in a broad vacuum-ultraviolet range and can be scaled up to higher
      output energies.

PMID- 19862030
TI  - Low-loss intracavity AlAs/AlGaAs saturable Bragg reflector for femtosecond mode
      locking in solid-state lasers.
AB  - We introduce a new low-loss semiconductor structure for femtosecond intracavity
      mode locking in low-gain solidstate lasers. This monolithic device can be
      engineered to exhibit specif ic saturation characteristics desirable for mode
      locking solid-state lasers. Self-starting 90-fs pulses are obtained with
      Ti:sapphire and diode-pumped Cr:LiSAF lasers. We discuss mode-locking mechanisms
      in quantum-well passively mode-locked solid-state lasers.

PMID- 19862031
TI  - Design of a bipolar composite filter by a simulated annealing algorithm.
AB  - We present the design of a bipolar composite filter (BCF) by a simulated
      annealing algorithm. By minimizing the energy function of the system, we
      construct an out-of-plane rotation-invariant bipolar filter. We show that the BCF
      offers high pattern discrimination capability and can easily be implemented with
      an electronically addressed spatial light modulator.

PMID- 19862032
TI  - Retardation and reduction of pulse distortion by group-velocity dispersion
      through pulse shaping.
AB  - We show that a reduction in the pulse distortion caused by chromatic dispersion
      can be achieved through pulse shaping. We argue that a simple binary phase mask
      in the Fourier plane of the laser spectrum can improve the transmission of short
      pulses in a dispersive channel through reduced broadening. The argument was
      tested experimentally, and a good agreement was found with the theory.

PMID- 19862033
TI  - Cascading the multiple stages of optical fractional Fourier transforms under
      different variable scales.
AB  - A simple but necessary condition for cascading the multiple stages of an optical
      fractional Fourier transform with different variable scales is presented. That
      condition permits more flexibility in the design of optical information
      processing systems that use optical fractional Fourier transforms. We have
      expanded the optical applications of fractional Fourier transforms with
      adjustable variable scales.

PMID- 19862034
TI  - Real-time three-dimensional display based on the partial pixel architecture.
AB  - We previously reported several static three-dimensional (3-D) display
      implementations of the partial pixel architecture [J. Opt. Soc. Am. A 12, 73
      (1995)]. We report herein our f irst real-time 3-D display based on this
      architecture. The display is functionally equivalent to a real-time holographic
      stereogram. It is autostereoscopic and provides horizontal motion parallax. The
      display device is composed of a diffractive optical element (fabricated with
      standard photolithographic techniques) and a separate conventional liquidcrystal
      display. The display has been used to play back a precomputed animated 3-D scene
      at video frame rates using a standard VGA video output.

PMID- 19862035
TI  - Determination of the xenon 6s[3/2](2)-6s'[1/2](0) clock frequency by
      interferometric wavelength measurements.
AB  - We have determined the wave number of the optical two-photon clock transition
      6s[3/2](2)-6s'[1/2](0) in xenon by interferometrically comparing the wavelengths
      of the 6s[3/2](2)-6p'[1/2](1) (lambda = 450 nm) and 6s'[(1/2)] (0)-6p'([1/2])
      (lambda = 764 nm) transitions with an iodine-stabilized 633-nm He-Ne laser. These
      measurements determine the frequency of the two-photon transition
      [4564.610902(13) cm(-1) for (132)Xe] to better than 1 MHz and provide precise
      values for the isotope shifts and the hyperfine structures of these transitions.

PMID- 19862036
TI  - Optical parametric loop mirror.
AB  - A novel configuration for four-wave mixing (FWM) is proposed that offers the
      remarkable feature of inherently separating the FWM wave from the input pump and
      signal waves and suppressing their background amplified stimulated emission
      without optical filtering. In the proposed configuration, an optical parametric
      loop mirror, two counterpropagating FWM waves generated in a Sagnac
      interferometer interfere with a relative phase difference that is introduced
      deliberately. FWM frequency-conversion experiments in a polarization-maintaining
      fiber achieved more than 35 dB of input-wave suppression against the FWM wave.

PMID- 19862037
TI  - Induced-dichroism-excited atomic line filter at 532 nm.
AB  - The operation of a narrow-linewidth optical f ilter based on the 4P((1/2)) ?
      8S((1/2)) excited-state transition in potassium vapor is reported. The 4P((1/2))
      state is excited by a circularly polarized, 769.9-nm, 10-ns pulse from a dye
      laser. A linearly polarized, time-sequenced, and spatially overlapped probe pulse
      at 532.33 nm completes the transition to the 8S((1/2)) state. The peak filter
      transmission is ~40% with a bandwidth of less than 4 GHz. Corroborative
      experimental results suggest that the rotation of probe-pulse polarization by an
      induced circular birefringence is the dominant mechanism behind the filter
      operation.

PMID- 19862038
TI  - 1 x 1104 holographic switching with a ferroelectric liquid-crystal spatial light
      modulator.
AB  - We demonstrate 1 x 1104 holographic switching with a ferroelectric liquid-crystal
      spatial light modulator to test the feasible output size of a holographic switch.
      The demonstration proves that switching was achieved when the power of a laser
      diode used as the control light source was 6.3 mW. The average of the insertion
      loss was 31.6 dB.

PMID- 19862039
TI  - Interferometric fiber-optic gyroscope performance owing to temperature-induced
      index fluctuations in the fiber: effect on bias modulation.
AB  - An analysis of the noise floor owing to temperature-induced index fluctuations in
      the fiber of a dynamically biased interferometric fiber-optic gyroscope is
      presented. A comparison with shot noise indicates that, for a harmonic bias
      modulation, thermal noise in the fiber dominates for fiber lengths longer than ~1
      2 km when practical source power levels are considered. The noise can be reduced
      or eliminated by the proper choice of modulation frequency or waveform.

PMID- 19862040
TI  - Efficient optical frequency-comb generator.
AB  - We have demonstrated a method that efficiently transfers the power from a single
      frequency laser into a wideband frequency comb. The comb was produced by a 2.7
      GHz electro-optic modulator in a resonant optical cavity. A coupled cavity
      technique was used to transfer 8.5% of the laser power into a comb with a span of
      400 modes, or more than 1 THz.

PMID- 19862041
TI  - Variable-spectral-=response optical waveguide Bragg grating filters for optical
      signal processing.
AB  - A simple method is described that permits the spectral response (spectral width,
      shape, and center resonant wavelength) of an optical waveguide Bragg grating to
      be controlled accurately in a prescribed manner. The control methodology consists
      of bonding the Bragg grating along the length of a mechanical support structure,
      which is then loaded with an appropriate force distribution. The function of the
      support structure is to transfer the strain induced by loading to the grating,
      thus modifying the grating's spectral response in accordance with the variation
      in effective optical pitch induced by the strain transfer. We design and
      demonstrate a support structure that provides independent control over the
      spectral width and center wavelength of a Bragg grating.

PMID- 19862042
TI  - High-efficiency subwavelength diffractive optical element in GaAs for 975 nm.
AB  - We have fabricated subwavelength diffractive optical elements with binary phase
      profiles for operation at 975 nm. The individual surface-relief features of the
      elements are smaller than the wavelength of light in the material. By modulating
      the size and spacing of the features we form artificial, gradient, effective
      index-of-refraction surfaces. The blazed transmission gratings were designed with
      rigorous coupled-wave analysis and fabricated by direct-write electron-beam
      lithography and reactive ion-beam etching in GaAs. The gratings have minimum
      features 63 nm wide. Transmission measurements show 85% diffraction efficiency
      into the first order.

PMID- 19862043
TI  - Improvement of spatial light modulator optical input/output performance using
      microlens arrays.
AB  - Advanced spatial light modulators both detect incident light and modulate
      reflected light. Each pixel may contain multiple photodetectors, a modulator,
      control circuitry, and signal-processing circuitry. Because each detector and
      modulator occupies only a fraction of the area of a pixel the optical efficiency
      of these devices suffers. We have experimented with improving optical
      input/output performance by integrating a microlens array with a ferroelectric
      liquid-crystal VLSI spatial light modulator. We have studied the microlens VLSI
      spacing accuracy that must be achieved to yield minimum distortion of ref lected
      wave fronts and the best optical efficiency for Fourier-transform applications.

PMID- 19862044
TI  - Interferometer using a 3 x 3 coupler and Faraday mirrors.
AB  - A new interferometric setup using a 3 x 3 coupler and two Faraday mirrors is
      presented. It has the advantages of being built only with passive components, of
      freedom from the polarization fading problem, and of operation with a LED. It is
      well suited for sensing time-dependent signals and does not depend on reciprocal
      or nonreciprocal constant perturbations.

PMID- 19862045
TI  - In situ reflectance measurements of soft-x-ray/extreme-ultraviolet Mo/Y
      multilayer mirrors.
AB  - With a new ultrahigh-vacuum deposition/ref lectometer system, Mo/Y multilayer
      mirrors were deposited by dc-magnetron sputtering and characterized in situ with
      synchrotron radiation. The Mo/Y multilayer mirrors, measured before exposure to
      air, had near-normal-incidence reflectances as high as 46% at wavelengths near
      11.4 nm. After several days of exposure these samples typically had a relative
      reflectance loss of ~10% as a result of oxidation of the top Mo layer. The best
      Mo/Y multilayers were fabricated with base pressures below the low 10(-9) Torr
      range and after a bakeout to reduce water vapor in the chamber.

PMID- 19862046
TI  - Polarization dependence of femtosecond soliton-soliton interactions in dispersion
      shifted fiber.
AB  - The polarization dependence of femtosecond soliton-soliton interaction in a
      dispersion-shifted fiber has been investigated in detail theoretically and
      experimentally. For 400-fs soliton pulses the input pulse separation at which the
      soliton-soliton interaction occurs is 1.6 ps for orthogonally polarized solitons
      as opposed to 2.3 ps when the polarizations are parallel. Similar to that in the
      parallel condition, the soliton self-frequency shift in the orthogonal case is
      accelerated through soliton-soliton interaction. However, the magnitude of the
      soliton self-frequency shift is reduced to one third of that in the parallel
      condition.

PMID- 19862047
TI  - Conjugation fidelity and bistability in a high-efficiency mutually pumped phase
      conjugator with ring channels.
AB  - We describe a high-efficiency mutually pumped phase conjugator with ring channels
      in a bird-wing incident geometry in copper-doped potassium sodium strontium
      barium niobate. A transmissivity as great as 35% is measured. Optical switching
      is obtained. The dependence of phase-conjugation fidelity on the geometric
      parameters and the input-beam ratio is discussed. Some suggestions are proposed
      to improve the fidelity further. The response times as a function of the input
      beam ratio with the input beam kept constant are measured, and the least-squares
      minimum is used to simulate the fitting curve equations and to explain the
      formation of optical switching and the reduction or improvement of image
      fidelity.

PMID- 19862048
TI  - Laser beam cleanup with photorefractive two-beam coupling.
AB  - The effectiveness of laser beam cleanup with photorefractive two-beam coupling is
      evaluated. We compare the measured effectiveness of the method with that of
      spatial filtering and find that the method works well for a highly aberrated beam
      approximately 700 times diffraction limited, whereas for moderately aberrated
      beams the effectiveness of the method is the same as that of spatial filtering.

PMID- 19862049
TI  - Fast optical switching in nonlinear prism couplers.
AB  - The excitation process of short optical pulses in waveguides by use of prism
      couplers is studied with a fully dynamic model. A good coupling efficiency is
      obtained even for short pulses. Fast nonlinear behavior such as power limiting
      and optical switching is predicted with a response time much shorter than the
      buildup time of the waveguide coupler. This new result is due to the group
      velocity matching between the guided and the pump fields.

PMID- 19862050
TI  - Light depolarization owing to amplified spontaneous emission and Kerr
      nonlinearity in long-haul fiber links close to zero dispersion.
AB  - The interplay between amplif ied spontaneous emission noise and Kerr nonlinearity
      is shown to produce significant depolarization of light in long-haul transmission
      links operating close to zero dispersion. If polarization mode dispersion is
      neglected, a simple analytical theory predicts the length scale over which
      depolarization occurs. The analytical theory is compared with computer
      simulations, which also permit analysis of the case in which polarization mode
      dispersion is included.

PMID- 19862051
TI  - Fabrication parameter optimization of a low-threshold high-efficiency proton
      exchanged waveguide laser in Nd:LiTaO(3).
AB  - Knowing the correlation between the Nd(3+) excited-state lifetime in proton
      exchanged waveguides and the phase diagram of the H(x)Li(1-x)TaO(3) compound
      permits optimized waveguide fabrication parameters to be found. These have been
      used to produce a Nd:LiTaO(3) waveguide laser with a threshold of 2.9 mW and a
      slope efficiency of 33%, in good agreement with the best predicted values.
      Nevertheless this component suffers from instabilities because of the
      photorefractive effect.

PMID- 19862052
TI  - Quasi-phase-matched parametric fluorescence in room-temperature lithium tantalate
      waveguides.
AB  - We report what is to our knowledge the f irst observation of quasi-phase-matched
      parametric fluorescence in the 1.2-2.3-microm region, at ambient temperature, in
      lithium tantalate waveguides, using a pump wavelength between 805 and 845 nm. The
      signal fluorescent power depends strongly on the proton concentration in the
      waveguide, and signals of up to 7 pW have been observed for guided pump powers of
      70 mW, which is 1 order of magnitude lower than the efficiency measured with
      lithium niobate guides.

PMID- 19862053
TI  - Room-temperature fluorozirconate glass fiber laser in the violet (412 nm).
AB  - Continuous oscillation on the (2)P(3/2) ? (4)I(11/2) transition of Nd(3+) in a f
      luorozirconate glass (ZBLAN) fiber at room temperature has been observed. When
      pumped at ~590 nm, a Nd:ZBLAN f iber 39 cm in length lases in the violet at 412
      nm and produces ~0.5 mW of power for 320 mW of pump power and a cavity output
      coupling of 0.4%. The breadth of the laser's excitation spectrum is ~12 nm (581
      593 nm).

PMID- 19862054
TI  - Channel waveguide laser at 1 microm in Yb-indiffused LiNbO(3).
AB  - We report laser action in a Ti-diffused LiNbO(3) waveguide doped with trivalent
      Yb ions by thermal indiffusion. Lasing was observed at 1008, 1030, and 1060 nm
      with thresholds as low as 15-mW launched pump power. We reduced
      photorefractivity, which initially permitted only intermittent lasing, by
      annealing the sample in wet O(2). The annealed sample lased continuously in a
      cavity formed by high-ref lectivity mirrors; however, with a 7% output coupler
      the output power exhibited instabilities. The greatest value of the output power
      observed under these conditions was consistent with a slope efficiency of ~16%
      with respect to absorbed power.

PMID- 19862055
TI  - Optical extraction efficiency in gas-flow lasers.
AB  - It is shown that the celebrated Rigrod model [J. Appl. Phys. 34, 2602 (1963)] is
      inadequate for calculating the output power of gas-f low lasers in an important
      range of parameters in which the quenching of the excited species is slow and the
      optical extraction eff iciency is high. For two-level systems very simple
      analytical formulas for the output power are obtained that should be used instead
      of the Rigrod model. The formulas are given for Fabry-Perot, stable, and unstable
      resonators. Both the saturation parameter and the extraction efficiency differ
      from those appearing in the Rigrod model. Applications of the formulas to systems
      with more complex kinetic schemes are also indicated.

PMID- 19862056
TI  - Effective index model for vertical-cavity surface-emitting lasers.
AB  - A new effective index optical model is presented for the analysis of lateral
      waveguiding effects in verticalcavity surface-emitting lasers. In addition to
      providing a concise formalism for reducing the dimensionality of the Maxwell
      equations describing the lasing mode, this model also provides new insights into
      waveguiding phenomena in vertical-cavity lasers. In particular, it is shown that
      the effective index responsible for waveguiding is dependent only on lateral
      changes in the Fabry-Perot resonance frequency. This concept leads naturally to
      new design methods for these lasers that are expected to result in more eff
      icient devices with superior modal characteristics.

PMID- 19862057
TI  - High-resolution optical coherence tomographic imaging using a mode-locked
      Ti:Al(2)O(3) laser source.
AB  - A Kerr-lens mode-locked Ti:Al(2)O(3) oscillator, optimized for minimal coherence
      length, is demonstrated as a high-power source for high-resolution optical
      coherence tomographic imaging. Dispersion compensation and heterodyne noise
      rejection are demonstrated to yield in situ images of biological tissues with 3.7
      mum resolution and 93-dB dynamic range.

PMID- 19862058
TI  - Transient properties of an electromagnetically induced transparency in three
      level atoms.
AB  - We describe the transient behavior of an electromagnetically induced transparency
      in three-level atomic systems. When the coupling f ield is switched on, the
      absorption for the probe field is oscillatorily damped to its new steady-state
      (transparent) value. Transient gain without population inversion and enhancement
      of dispersion are discussed. A realistic system for experimental testing of these
      effects is presented.

PMID- 19862059
TI  - Microcavity transverse coherence length and microlaser threshold.
AB  - The concept of transverse coherence length in an active microscopic cavity is
      investigated with regard to the threshold of the microlaser action. This physical
      parameter is related to the linear spatial extent, or the effective radius, of
      the transverse lasing mode operating in a plane Fabry-Perot microcavity. This
      problem is analyzed by means of a full semiclassical theory, by which the
      microlaser threshold is expressed as a function of the relevant parameters of the
      thresholdless microlaser and of the extension of the active pumped zone.
      Experimental results are in satisfactory agreement with the theoretical
      predictions.

PMID- 19862060
TI  - Multiple-hologram storage for thin layers of Methyl Orange dyes in polyvinyl
      alcohol matrices.
AB  - We realized hologram storage within a 0.07-cm(2) light spot in thin layers of
      polyvinyl alcohol matrices doped with Methyl Orange dyes preirradiated by the
      488.0-nm line of an Ar-ion laser with two orthogonal linearly polarized 632.8-nm
      light beams. By rotation of the sample, multiple-hologram storage was achieved.
      By controlling the writing time, we have recorded three-hologram and f ive
      hologram images in the same light spot. The mechanism of the multiple-hologram
      storage in Methyl Orange-doped polyvinyl alcohol thin films is discussed.

PMID- 19862061
TI  - Fourier spatial filter acts as a temporal gate for light propagating through a
      turbid medium.
AB  - The temporal profiles of ultrashort light pulses propagating through turbid media
      of different lengths were measured with a streak camera. Various Fourier spatial
      filters were used to select the spatial frequencies of the scattered pulses. The
      temporal profiles of the pulses scattered by a 0.4% Intralipid solution in a cell
      of 5-cm thickness were signif icantly narrowed because of the removal of the
      higher-frequency components by a Fourier spatial filter.

PMID- 19862062
TI  - Extraction of quasi-straightforward-propagating photons from diffused light
      transmitting through a scattering medium by polarization modulation.
AB  - The utilization of light polarization is proposed to extract quasi
      straightforward-propagating photons from diffused light transmitting through a
      scattering medium under continuously operating conditions. Removal of a floor
      level normally appearing on the dynamic range over which the extraction
      capability is maintained is demonstrated. By use of pulse-based observations this
      cw scheme of extraction of quasi-straightforwardpropagating photons is directly
      shown to be equivalent to the use of a temporal gate in the pulse-based
      operation.

PMID- 19862063
TI  - Wave-front analysis using Fresnel lens arrays.
AB  - A compact wave-front sensor is implemented by an array of two-beam common path
      inversion interferometers. Each element of the array consists of two Fresnel
      lenses in a confocal configuration. The wave-front data can be extracted from a
      superposition of the zero-order undiffracted wave and the twice-diffracted first
      order wave. The result is a high-sensitivity, compact, and stable interferometric
      wave-front sensor.

PMID- 19862064
TI  - Demonstration of a power-recycled Michelson interferometer with Fabry-Perot arms
      by frontal modulation.
AB  - Large-scale gravitational-wave detectors currently under construction such as the
      LIGO detectors use multiplemirror resonant optical systems containing several
      surfaces at which the relative phase of interfering light beams must be
      controlled. We describe a tabletop experiment that demonstrates a scheme for
      extracting signals in such an interferometer corresponding to deviations from
      perfect interference.

PMID- 19862065
TI  - Programmable diffractive optical element using a multichannel lanthanum-modified
      lead zirconate titanate phase modulator.
AB  - We introduce a programmable diffractive optical element based on an electro-optic
      phased array implemented with a multichannel lanthanum-modified lead zirconate
      titanate phase modulator. The design and fabrication procedures are outlined,
      along with an experimental demonstration of the device. Experimental results from
      a 16-channel device operating with a 2pi ; voltage of 300 V demonstrate selective
      beam steering. The programmable diffractive optical element allows for efficient,
      high-speed high-resolution random-access optical beam steering over a continuous
      scanning range.

PMID- 19862066
TI  - High-efficiency multilayer dielectric diffraction gratings: erratum.

PMID- 19862067
TI  - Mapping whispering-gallery modes in microspheres with a near-field probe.
AB  - We demonstrate the use of a near-field probe to map the angular dependence of
      high-Q whispering-gallery modes in fused-silica microspheres. The mapping is
      performed by placing a micrometer-sized tip formed on the end of a monomode fiber
      into the evanescent f ield at the microsphere surface, causing light to be
      coupled from the microsphere resonance into the fiber guided mode. The light
      output of the fiber is then measured while the tip is moved to different points
      on the microsphere surface. We have used this method to investigate the lifting
      of spherical degeneracy in the system.

PMID- 19862068
TI  - Low-power phase conjugation in push-pull azobenzene compounds.
AB  - Push-pull azobenzene compounds were synthesized by the diazocoupling reaction,
      and low-power phase conjugation of azobenzene-compound-doped poly(methyl
      methacrylate) films was studied with a He-Ne laser at 632.8 nm. It is shown that
      this kind of polymer has appreciable third-order optical nonlinearity, with a
      chi((3)) of approximately 10(-4) esu in the tail of absorption.

PMID- 19862069
TI  - Linear transformation of pulse chirp through a cascaded optical second-order
      process.
AB  - We have experimentally investigated the combination of chirps of two ultrashort
      light pulses through self diffraction induced by cascaded second-order frequency
      mixing in a beta-barium borate crystal. Interaction of two pulses with equal
      carrier frequencies and opposite chirps yielded diffracted pulses with enhanced
      chirp. Perfect compressibility of the diffracted pulse indicates that phase
      distortion by intensity-dependent effects was negligible.

PMID- 19862070
TI  - Three-photon-absorption-induced fluorescence and optical limiting effects in an
      organic compound.
AB  - Three-photon-absorption-induced frequency-upconversion f luorescence emission has
      been observed in a solution of 2,5-benzothiazole 3,4-didecyloxy thiophene
      (BBTDOT) in tetrahydrofuran, pumped with 10-ns Q-switched 1.06-microm laser
      pulses. The spectral peak of the observed fluorescence emission is located in the
      450-480-nm range, and the intensity dependence of the visible emission on the IR
      excitation obeys the cubic law. At a higher solute concentration (0.18 M/L) and
      moderate IR excitation intensity levels (50-200 MW/cm(2)), obvious optical
      limiting behavior has been observed as a result of three-photon absorption. The
      measured nonlinear absorption coeff icient and the corresponding molecular three
      photon-absorption cross section are gamma= 2.7 x 10(-18) cm(3)/W(2) and sigma'(3)
      = 8.8 x 10(-76) cm(6) s(2), respectively.

PMID- 19862071
TI  - Instabilities of dark solitons.
AB  - Optical dark solitons described by the generalized nonlinear Schrodinger equation
      are discussed, and the criterion of soliton instability is presented. This
      analytical criterion is confirmed numerically for an exactly solvable model of
      nonlinear saturation.

PMID- 19862072
TI  - Holographic scattering lines and mirrorless oscillation in BaTiO(3).
AB  - Four scattering lines are observed on a screen behind a BaTiO(3) sample pumped by
      two ordinary copropagating waves. If in addition counterpropagating pump waves
      meeting the same phase-matching condition are introduced, mirrorless oscillation
      occurs.

PMID- 19862073
TI  - Observation of electro-optic and electroabsorption modulation in a Langmuir
      Blodgett film Fabry-Perotetalon.
AB  - Electro-optic and electroabsorption modulation by use of a Langmuir-Blodgett (LB)
      film-based Fabry-Perot etalon is reported. The modulation was found to be
      dominated by linear effects in the film. The percentage change in transmission
      was 15% for electro-optic and 30% for electroabsorption modulation at an rms
      drive voltage of 53 V. The effective linear electro-optic coefficient of the LB
      film was 13 pm V(-1) at 633 nm for s-polarized light. We believe that this is the
      highest value reported to date for thick LB films.

PMID- 19862074
TI  - Nondestructive method for attenuation measurements in optical hollow waveguides.
AB  - A new method for characterizing hollow waveguides has been developed in which the
      laser radiation is coupled into the waveguide hollow bore through an optical
      fiber. By moving the distal end of the fiber along the waveguide we achieved
      scanning of the incident radiation in the waveguide at various points on the
      internal walls. This method can be employed for measuring attenuation without
      cutback or for detecting point defects on the waveguide's guiding layers.

PMID- 19862075
TI  - Efficient continuous-wave lasing operation of Nd:KGd(WO(4))(2) at 1.067 microm
      with diode and Ti:sapphire laser pumping.
AB  - We describe the efficient operation of a Nd:KGd(WO(4))(2) laser at 1.067 microm
      pumped by Ti:sapphire and diode lasers. Preliminary data indicate a relatively
      low threshold and high efficiency for a 10 mm diameter x 10 mm long
      antireflection-coated crystal. The wide high-absorption band was centered near
      810 nm. The fluorescence lifetime was 109 micros, and the stimulated-emission
      cross section was approximately 3.5 x 10(-19) cm(2). Slope efficiencies of 43%
      and 44% were attained for diode laser and Ti:sapphire pump sources, respectively.

PMID- 19862076
TI  - Diode-pumped Nd:YLF all-in-one laser.
AB  - A high-power longitudinally end-diode-pumped Nd:YLF all-in-one laser has been
      constructed and tested. The compact single-cavity laser generates pulses with
      durations of 28 ps. Pulse energies of ~120 or -500 microJ are measured at a 1-kHz
      repetition rate when the all-in-one laser is pumped with a 3- or 15-W diode
      laser, respectively. Controlled prelasing is utilized to prevent the buildup of
      large-amplitude relaxation oscillations and to minimize the prelasing leakage.
      Pulse shaping in the all-in-one laser is analyzed in terms of the Kuizenga
      Siegman theory.

PMID- 19862077
TI  - Gigahertz planar photoconducting antenna activated by picosecond optical pulses.
AB  - We have generated 1-20-GHz microwave pulses by illuminating an Fe-compensated InP
      wafer with 50-ps optical pulses at normal incidence. The process of the
      generation of microwave radiation was monitored and analyzed directly through a
      40-GHz sampling oscilloscope with precision. The saturation properties, the
      waveform evolution, and the optical coupling efficiency of the gigahertz
      photoconducting antenna are discussed. The flexibility, compactness, and high
      resolution features offered by this technique merit new applications for radar
      communication as well as for other microwave detecting devices.

PMID- 19862078
TI  - Time-dependent analysis of a parametric lens detected with a 100-fs Ti:sapphire
      laser.
AB  - The second-order parametric lens effect shows a temporal limit as a saturable
      absorber device for operation in the ultrafast time region. We present and
      discuss an extended theoretical model dealing with second-order cascaded
      processes in a nonstationary condition. Experimentally we report the detection of
      the time-averaged lens effect in the hundred-of-femtoseconds range, discussing
      the limits that arise in this ultrafast optical region.

PMID- 19862080
TI  - Electro-optic phase modulator as a starting mechanism in Ti:sapphire.
AB  - An electro-optic phase modulator in a regenerative mode-locker configuration is
      demonstrated as the starting mechanism for a Kerr-lens mode-locked Ti:sapphire
      laser. Mode locking is initiated automatically, and the system is capable of
      pulses as short as 21 fs.

PMID- 19862079
TI  - Femtosecond Sagnac interferometer for phase spectroscopy.
AB  - We developed a novel femtosecond Sagnac interferometer that enables us to take
      single-shot measurements of both the difference transmission and the difference
      phase spectra. Owing to the excellent stability of the Sagnac interferometer, a
      difference phase spectrum was obtained with a high phase change sensitivity of
      ~lambda/100 after a 1000-shot accumulation. The spectral range, wavelength, and
      time resolution were 530-650 nm, 1 nm, and 200 fs, respectively.

PMID- 19862081
TI  - Cascaded second-order effects in the femtosecond regime in beta-barium borate:
      self-compression in a visible femtosecond optical parametric oscillator.
AB  - Cascaded second-order effects are studied in the femtosecond regime in beta
      barium borate by use of the Z-scan technique. Large nonlinear phase shifts can be
      obtained near the second-harmonic-generation phasematching condition for a
      Ti:sapphire laser. Solution of the nonlinear propagation equations for
      femtosecond pulses yields good agreement with experiment and also demonstrates
      that the description of cascaded effects by an effective nonlinear refractive
      index is no longer valid in the ultrafast domain and that these effects are less
      efficient for ultrashort pulses. The cascade-induced negative nonlinear phase
      shift in beta-barium borate is shown to be responsible for the self-compression
      observed in a prismless femtosecond visible optical parametric oscillator.

PMID- 19862082
TI  - Scaling of the antiresonant Fabry-Perot saturable absorber design toward a thin
      saturable absorber.
AB  - We demonstrate and discuss the scaling of the antiresonant Fabry-Perot saturable
      absorber toward a novel antiref lection-coated thin saturable absorber. With a
      Ti:sapphire laser we obtained self-starting Kerr-lens mode-locked pulses as short
      as 19 fs. With the higher modulation depth of the thin saturable absorber we
      obtained soliton mode-locked self-starting 34-fs pulses over the full cavity
      stability regime with a significantly shorter mode-locking buildup time. The
      pulse duration was limited only by the semiconductor Bragg mirror.

PMID- 19862083
TI  - Sub-20-fs tunable pulses in the visible from an 82-MHz optical parametric
      oscillator.
AB  - We have produced pulses tunable in the 590-666-nm range, with durations down to
      13 fs, using an 82-MHz Ti:sapphire second-harmonic-pumped, high-bandwidth, beta
      barium borate optical parametric oscillator in a fused-silica prism group-delay
      dispersion-compensated, six-mirror folded ring cavity.

PMID- 19862084
TI  - Compact lenslet-array-based holographic correlator/convolver.
AB  - Although electronic systems continue to shrink in size, optical processors,
      particularly correlators/convolvers, remain relatively bulky. Here a compact
      holographic correlator/convolver, based on the use of multiple lenslet arrays, is
      presented. This compact lenslet-array holographic correlator/convolver approach
      offers most of the advantages of conventional optical correlators, including
      fully parallel high-speed operation, yet its physical size is comparable with
      that of monolithic optoelectronic units such as VLSI spatial light modulators and
      CCD's. Thus hybrid optoelectronic systems based on the lenslet-array holographic
      correlator/convolver (pattern recognition, optically interconnected computers,
      artificial neural networks, etc.) can be both compact and fast.

PMID- 19862085
TI  - Low-noise preamplifier for multistage photorefractive image amplification.
AB  - We present a two-beam coupling configuration in photorefractive BaTiO(3) that
      provides a low-noise amplification of the signal to be detected. A two-wave
      mixing gain of 100 is reached, in conjunction with very low beam fanning
      background in the signal direction. The extensions of this configuration to
      photorefractive heterodyne detection and to multistage image amplif ication are
      theoretically and experimentally studied.

PMID- 19862086
TI  - Interferometric technique for the measurement of photonic band structure in
      colloidal crystals.
AB  - Under suitable conditions polystyrene microsphere colloids form photonic crystals
      capable of diffracting visible light, analogous to x-ray diffraction from atomic
      crystal planes. The lattice spacings of these crystals can be tailored to satisfy
      the Bragg condition along a certain direction for a particular desired
      wavelength. A modified Mach-Zehnder interferometer has been developed for
      accurately measuring relative phase shifts of light propagating in photonic
      crystals to determine the dispersion resulting from photonic band structure near
      the band edges.

PMID- 19862087
TI  - Speckle spectroscopy with tip-tilt operation.
AB  - A stellar speckle spectrometer with tip-tilt operation is proposed for high
      spatial-resolution spectroscopy under atmospheric turbulence. A specklegram is
      used to drive a tip-tilt mirror for real-time shift-and-add operation to its
      dispersed specklegram. The proposed speckle spectroscopy attains a long exposure
      for the spectrum and a slit spectrometer. Several simulation experiments confirm
      the effectiveness of our method.

PMID- 19862088
TI  - Measurement of gas-phase sound speed and thermal diffusivity over a broad
      pressure range using laser-induced thermal acoustics.
AB  - We report on the detection and analysis of signals generated from gas-phase laser
      induced gratings over a large range of static pressure (0.04-100 atm). We
      employed the experimental technique of laser-induced thermal acoustics and
      performed measurements on mixtures of NO(2) in air and CO(2) as a function of
      pressure. Accurate analysis of the acquired data was obtained from a full theory,
      including beam size effects. The theory fully reproduces the observed data for a
      ratio of molecular mean free path to grating wavelength extending from 1 to 4 x
      10(-4). Nonlinear, least-squares f its between modeled and experimental signals
      provided accurate values of the sound speed and thermal diffusivity.

PMID- 19862089
TI  - Observation of light diffraction by time-resolved femtosecond correlation
      interferometry.
AB  - We demonstrate time development of the diffraction of light waves from objects
      for what is to our knowledge the f irst time by using a new femtosecond
      correlation interferometry. This new dynamical optics method allows for the
      conversion of temporal information to space information with femtosecond
      resolution and has the potential to produce a time-resolved femtosecond movie for
      the visualization of light-wave propagation in space for scientific, biological,
      and medical applications.

PMID- 19862090
TI  - Closed-loop adaptive-optics system with a liquid-crystal television as a phase
      retarder.
AB  - We present a closed-loop adaptive-optics system that uses a liquid-crystal
      television (LCTV) as a phase retarder. The system consists of a LCTV inserted
      into one leg of a Mach-Zehnder interferometer so that one measures the wave-front
      function by analyzing the interferogram using a video CCD camera and a computer
      and corrects the wave-front distortion by placing the conjugate function on the
      LCTV. Experimental results are presented.

PMID- 19862091
TI  - All-fiber dispersive transmission filters based on fiber grating reflectors.
AB  - A novel, low-insertion-loss transmission f ilter with the implementation of
      linearly chirped fiber Bragg grating reflectors and polarization-splitting fiber
      fusion couplers is reported. Pulse chirping, chromatic dispersion compensation,
      and pulse compression are demonstrated. Cascading of dispersive filters,
      including application to a low-loss pulse stretchery/recompressor of femtosecond
      pulses, is also demonstrated.

PMID- 19862093
TI  - Correlation of Ge E' defect sites with second-harmonic generation in poled high
      water fused silica.
AB  - Second-harmonic generation (SHG) in poled high-water fused silica was found to be
      linearly dependent on the relative concentration of Ge E' defect sites (<10(-15)
      defect sites/cm(3)) for the highly pure UV-grade material. For commercial-grade
      material characterized by higher concentrations of Ge E' defects sites, the SHG
      appeared to saturate at approximately 0.5 pm/V. No dependence of the SHG was
      found on the relative concentration of Ge E' defects sites in poled commercial
      grade low-water fused silica.

PMID- 19862092
TI  - Radial profiling of microdroplets using cavity-enhanced Raman spectroscopy.
AB  - The composition of 7.7-microm-radius methanol-water droplets was radially
      resolved by cavity-enhanced Raman spectroscopy. Optical cavity modes,
      encompassing well-defined radial zones within each droplet, were sequentially
      excited by a 514.5-nm laser beam to generate spontaneous Raman scattered light.
      The cavity-enhanced Raman spectral peaks gave information as to the identity and
      amount of species present. The measured radial and time dependence of the
      methanol concentration agreed with a diffusion-limited evaporation mode.

PMID- 19862094
TI  - Transistor action through nonlinear cascading in Type II interactions.
AB  - Based on cascading through Type II second-harmonic generation, I show how all
      optical amplitude modulation and switching can be obtained by utilizing an input
      wave at the fundamental frequency with unequal orthogonal spatial components. The
      proposed all-optical transistor/switch is insensitive to the inputs' relative
      phase, representing a step forward with respect to previously suggested
      configurations for transparent photonic networks.

PMID- 19862095
TI  - Vector theory of self-focusing of an optical beam in Kerr media.
AB  - The scalar theory of the self-focusing of an optical beam is not valid for a very
      narrow beam, and a correct description of the beam behavior requires a vector
      analysis in this case. A vector nonparaxial theory is developed from the vector
      Maxwell equations by application of an order-of-magnitude analysis method. For
      the same input beam, the numerical results of self-focusing from both scalar and
      vector theories are compared. It is found by the vector theory that a linearly
      polarized circular input beam becomes elliptical in the selffocusing process.

PMID- 19862096
TI  - Spectral filtering of solitons by means of a nonlinear amplifying loop mirror.
AB  - Soliton evolution in optical fibers and all-optical soliton recovery with a
      nonlinear active loop mirror have been studied with view to applications in
      transmission systems having a high bit-rate-]distance product. A 1.3-ps pulse is
      successfully transmitted over 111 soliton periods, reshaped, amplif ied, and
      transmitted another 111 soliton periods.

PMID- 19862097
TI  - Photorefractive semiconductor single-mode waveguides grown by gas-source
      molecular-beam epitaxy.
AB  - Two semiconductor single-mode waveguides have been fabricated to study the
      photorefractive effect in epilayers grown on an InP:Fe substrate. The first
      experimental results obtained in these structures are reported. At 1.55-microm
      wavelength, a 0.53-cm(-1) gain is observed in contradirectional two-wave mixing
      and a 4-cm(-1) gain is measured in codirectional two-wave mixing with a 5.7-kV/cm
      applied field. The gain dependence versus the light intensity and the applied
      field is also discussed.

PMID- 19862098
TI  - Nonlinear-optical activity owing to anisotropy of ultrafast nonlinear refraction
      in cubic materials.
AB  - The evolution of the polarization state in a cubic material with an anisotropic
      Kerr nonlinearity is examined. It is shown that in certain cases this provides a
      mechanism for nonlinear-optical activity, leaving the state of the polarization
      unchanged but causing a signif icant rotation in its major axis. The use of the
      anisotropic ultrafast nonlinear refraction that exists just beneath the half-gap
      in semiconductors to demonstrate these effects is discussed.

PMID- 19862099
TI  - Double phase-conjugate mirror: to oscillate, or not to oscillate?
AB  - A physical picture of the differences in operation of the photorefractive double
      phase-conjugate mirror for TM versus TE polarization is presented.

PMID- 19862100
TI  - Picosecond degenerate four-wave mixing in colloidal solutions of gold
      nanoparticles at high repetition rates.
AB  - Time-resolved degenerate four-wave mixing experiments on a colloidal solution of
      50-nm gold particles in acetone, using a high-repetition-rate laser source, are
      presented. The signal is found to depend strongly on the repetition rate of the
      incident radiation and above a frequency of 300 kHz is impossible to measure.

PMID- 19862101
TI  - Soliton transmission control with semiconductor amplifiers.
AB  - A signal propagating along a dispersive transmission line in which loss is
      compensated by semiconductor amplifiers suffers from strong memory effects
      induced by the amplifier saturation. Insertion of filters along a line of
      anomalous dispersion reduces the detrimental effects of the amplifier saturation.

PMID- 19862102
TI  - Oscillator strengths of UV absorption and luminescence for oxygen-deficient
      centers in germanosilicate fibers.
AB  - The time-resolved measurements of triplet and singlet luminescence from germanium
      oxygen-deficient centers (GODC's) in germanosilicate fibers excited by short UV
      laser pulses are used to determine the cross section of UV absorption of GODC's
      at lambda = 248 nm (sigma = 5 x 10(-18) cm(2)), the oscillator strength of UV
      absorption (f(abs) = 0.027), and UV luminescence (f(lum) = 0.031). The basis for
      these measurements is the direct luminescence detection of lifetimes of
      electronically excited states of GODC's, the saturation of triplet luminescence
      signals, and the analysis of the rate equations that govern the laser
      photoexcitation and relaxation processes in GODC's.

PMID- 19862103
TI  - Extended IWKB method for determination of the refractive=index profile in optical
      waveguides.
AB  - A simple method is outlined for the calculation of the refractive-index profiles
      of both multimode and monomode planar optical waveguides. The method is an
      extension of the well-established IWKB method. The parameters required are the
      dispersion relation of the surface index changes and the effective indices at
      different wavelengths. As an example, the refractive-index profile of a monomode
      z-cut KTiOPO(4) planar waveguide fabricated by Rb(+):K(+) exchange is computed.
      Close agreement is obtained, indicating the practicality of this method. The
      method is also applicable to optical waveguides in other materials, such as
      LiNbO(3), LiTaO(3), and glass.

PMID- 19862104
TI  - Environmentally stable high-power soliton fiber lasers that use chirped fiber
      Bragg gratings.
AB  - Environmentally stable high-power erbium fiber soliton lasers are constructed by
      Kerr or carrier-type mode locking. We obtain high-energy pulses by using
      relatively short fiber lengths and providing large amounts of negative dispersion
      with chirped fiber Bragg gratings. The pulse energies and widths generated with
      both types of soliton laser are found to scale with the square root of the cavity
      dispersion. Kerr mode locking requires pulses with an approximately three times
      higher nonlinear phase shift in the cavity than carrier mode locking, which leads
      to the generation of slightly shorter pulses with as much as seven times higher
      pulse energies at the mode-locking threshold.

PMID- 19862105
TI  - Effects of dispersion on mode locking in optical parametric oscillators.
AB  - We discuss the role that group-velocity dispersion and cavity detuning play in
      the onset of mode locking in synchronously pumped optical parametric oscillators.
      Because of the phase-sensitive character of the parametric gain, it is shown for
      the degenerate case that dispersion effects associated with off-resonance
      operation can lead to subpulse structures and spectral splitting of the
      parametric pulses. This behavior is interpreted on the basis of a dispersion
      induced interference phenomenon between the two nearly degenerate parametric
      photons produced by the conversion of one pump photon in the nonlinear medium.

PMID- 19862106
TI  - Broadband light generation by femtosecond pulse amplification with stimulated
      Raman scattering in a high-power erbium-doped fiber amplifier.
AB  - It is shown for the first time to our knowledge that short-pulse amplification in
      high-power erbium-doped fiber amplifiers, simultaneously accompanied by
      stimulated Raman scattering, generates a broadband optical spectrum at high
      output power (270 mW). At 20 dB down from the peak the continuum extended over
      329 nm, from 1427 to 1756 nm. The FWHM bandwidth was 125 nm, centered at 1650 nm.
      The coherence was measured to be 15 fringes, which corresponds to a 25-microm
      coherence length.

PMID- 19862107
TI  - Tunable phase conjugation in a Ti:sapphire amplifier.
AB  - Four-wave mixing by gain saturation in a laser-pumped Ti:sapphire
      (Ti(3+):Al(2)O(3)) amplif ier is demonstrated for the f irst time to our
      knowledge. Small-signal gain in excess of 250 has been obtained by intense laser
      pumping at 532 nm, resulting in observed four-wave mixing energy ref lectivity as
      high as 360% for nanosecond pulses at 780 nm.

PMID- 19862108
TI  - Bandwidth characteristics of a pulsed optical parametric oscillator: application
      to degenerate four-wave mixing spectroscopy.
AB  - Factors influencing the optical bandwidth of a free-running pulsed beta-barium
      borate optical parametric oscillator are examined and incorporated in a simple
      fitting procedure. Spatiospectral phenomena in the optical parametric oscillator
      output beam are thereby identified; these suggest a novel way to reduce the
      effective optical bandwidth for spectroscopic purposes. This technique is
      demonstrated by recording a degenerate fourwave mixing spectrum of sodium atoms
      in an air-acetylene flame.

PMID- 19862109
TI  - Tunable UV generation at 286 nm by frequency tripling of a high-power mode-locked
      semiconductor laser.
AB  - We produced ultraviolet radiation by frequency tripling the mode-locked emission
      of an external cavity laser containing a tapered GaAlAs amplif ier gain element.
      The 429-nm second harmonic produced by a KNbO(3) crystal was sum-frequency mixed
      with the 858-nm fundamental in a Li(3)BO(5) crystal, generating as much as 50
      microW of power at 286 nm.

PMID- 19862110
TI  - Highly nondegenerate four-wave mixing in semiconductor laser oscillators.
AB  - A complete model to evaluate frequency conversion that is due to highly
      nondegenerate four-wave mixing in Fabry-Perot laser oscillators is presented;
      propagation effects are taken into account. Simplified expressions are obtained
      in the limit of perfectly reflecting mirrors that permit analytical solutions;
      they are in good agreement with the results of the numerical analysis. Examples
      of results exhibit interesting features such as a correction factor for the
      relaxation frequency peak, good conversion gain up to the terahertz region, and
      complex behavior of the frequency response near side-mode resonances.

PMID- 19862111
TI  - Far-infrared terahertz time-domain spectroscopy of flames.
AB  - We present what is to our knowledge the first comprehensive far-infrared
      absorption measurement of flames. These measurements, covering the region of 7-88
      wave numbers (0.2-2.65 THz) are only now made possible by the technique of
      terahertz time-domain spectroscopy. We observe a large number of absorption lines
      including those of water, CH, and NH(3)-in a stationary, premixed, propane-air
      flame. The absorption strength permits the determination of species concentration
      along the beam path. The f lame temperature is determined by comparison of the
      relative strengths of the water vapor lines.

PMID- 19862112
TI  - Squeezing in a quasi-phase-matched LiNbO(3) waveguide.
AB  - We report traveling-wave quadrature squeezing at 1064 nm in a quasi-phase-matched
      LiNbO(3) waveguide, avoiding the gain-induced diffraction encountered in bulk
      squeezing experiments. The 10-mm-long singlemode waveguide parametric amplifier
      exhibited a gain of 1.9, averaged over the 20-ps mode-locked pulses, with only
      0.5 W of peak pump power at 532 nm. Independent waveguides were employed for the
      degenerate parametric amplifier squeezer and for the second-harmonic generator
      that produced the pump for the parametric amplifier. We measured phase-sensitive
      amplification versus pump power and found close agreement with theory. The
      observed 14% squeezing correlates closely with the predicted value, based on the
      measured phase-sensitive amplification and 40% overall detection efficiency.
      Impedance-matched electrically resonant detection was used to boost our squeezing
      measurement signals substantially above the background level.

PMID- 19862113
TI  - Simultaneous acquisition of pi/2 phase-stepped interferograms with a
      photorefractive Bi(12)GeO(20) crystal: application to real-time double-pulse
      holography.
AB  - We present a novel method for real-time analysis of vibrations in double-pulse
      laser holography. Two pi/2 phase-stepped interferograms are obtained
      simultaneously. An experimental demonstration gives a phase measurement with an
      accuracy of 4 degrees .

PMID- 19862114
TI  - Error-correcting code for volume holographic storage of a relational database.
AB  - We present an error-correcting code suitable for encoding relational database
      information to be stored in a volume holographic memory system. The code makes
      use of the page-oriented format of holographic memories as well as the tabular
      arrangement of database records. The performance metrics discussed here show that
      the code results in industry-standard bit error rates and permits simple and fast
      decoding.

PMID- 19862115
TI  - Demonstration of 8-Gbit/in.(2) areal storage density based on swept-carrier
      frequency-selective optical memory.
AB  - Using swept-carrier frequency-selective optical data storage techniques to record
      multikilobit-long data streams at single spatial locations, we have achieved an
      areal storage density of 8 Gbits/in.(2) and a density-input/output bandwidth
      product of 1.5 x 10(17) bits/(in.(2) s). The latter quantity is among the highest
      demonstrated in the context of nonparallelized two-dimensional optical or
      magnetic recording systems. Extrapolation of the present results to full material
      utilization suggests an achievable storage density of the order of 100
      Gbits/in.(2).

PMID- 19862116
TI  - Multiplexed heterodyne fiber interferometer that uses laser-diode modulation.
AB  - An interferometer has been developed that uses a bundle of fibers and a current
      modulated laser diode. Light from the laser diode is distributed to three fibers
      whose exit ends are fixed together, and fiber lengths are chosen so that their
      differences will not be equal. From the phase of separated heterodyne signals
      produced between the reference and the sensor fibers we can detect the change in
      optical path length that is caused in the sensor fibers by external
      perturbations. As an application, temperature sensing at two points has been
      demonstrated.

PMID- 19862117
TI  - Enhanced backscattering from a volume-scattering medium behind a phase screen.

PMID- 19862118
TI  - Temperature-dependent wavelength shifts of dye lasing in microdroplets with a
      thermochromic additive.

PMID- 19862119
TI  - Soliton logic gate using low-birefringence fiber in a nonlinear loop mirror.

PMID- 19862121
TI  - Coupled solitons in waveguides with second- and third-order nonlinearities.

PMID- 19862120
TI  - Gap soliton propagation in optical fiber gratings.

PMID- 19862122
TI  - Optimum conditions for soliton launching from chirped sech2 pulses.

PMID- 19862123
TI  - Polarization-dependent mechanism transformation during self-pumped phase
      conjugation in BaTiO3:Ce.

PMID- 19862124
TI  - Analytical approach to all-optical modulation by cascading.

PMID- 19862125
TI  - Very high-gain two-wave mixing in BaTiO3 with a self-bent pump beam.

PMID- 19862127
TI  - Quantum key distribution over distances as long as 30 km.

PMID- 19862126
TI  - Enhancement of third-harmonic blue-violet light at 440 nm by erbium ions in Er3
      (+) -GeO2 -doped silica monomode optical fibers pumped at 1.319 mu m.

PMID- 19862128
TI  - Control of proton exchange for LiTaO3 waveguides and the crystal structure of
      HxLi1 - xTaO3.

PMID- 19862129
TI  - High-power neodymium soliton fiber laser that uses a chirped fiber grating.

PMID- 19862130
TI  - Self-adaptive solid-state laser oscillator formed by dynamic gain-grating
      holograms.

PMID- 19862131
TI  - Continuous-wave TEM00-mode 26.5-W-output virtual-point-source diode-array-pumped
      Nd:YAG laser.

PMID- 19862132
TI  - Nd:YAG amplifier with a semiconductor phase-conjugate mirror.

PMID- 19862133
TI  - Response of fiber lasers to an axial magnetic field.

PMID- 19862134
TI  - Imaging with terahertz waves.

PMID- 19862135
TI  - Electro-optic systolic processor with a pipeline architecture.

PMID- 19862136
TI  - Optical pattern recognition based on color vision models.

PMID- 19862137
TI  - Detection of CN by degenerate four-wave mixing.

PMID- 19862138
TI  - All-optical parallel-to-serial conversion by holographic spatial-to-temporal
      frequency encoding.

PMID- 19862139
TI  - Optical interference fringe reduction in frequency-modulation spectroscopy
      experiments.

PMID- 19862140
TI  - Micromotor grating optical switch.

PMID- 19862141
TI  - Fiber-optic pseudodepolarizer based on birefringence modulation.

PMID- 19862142
TI  - All-fiber magneto-optic isolator based on the nonreciprocal phase shift in
      asymmetric fiber.

PMID- 19862143
TI  - Nondiffracting images under coherent illumination.

PMID- 19862144
TI  - Second-harmonic generation in local modes of a truncated periodic structure.

PMID- 19862145
TI  - Intensity-dependent polarization rotation associated with type II phase-matched
      second-harmonic generation: application to self-induced transparency.

PMID- 19862146
TI  - Suppression of interactions between adjacent optical dark solitons by means of
      synchronized phase modulation.

PMID- 19862147
TI  - Buildup of spontaneous hexagonal patterns in photorefractive BaTiO3 with a
      feedback mirror.

PMID- 19862149
TI  - Analytic spatial solitary wave modes of the coupled-wave-carrier equations in a
      semiconductor waveguide.

PMID- 19862148
TI  - Optical switching in nonlinear waveguide arrays with a longitudinally decreasing
      coupling coefficient.

PMID- 19862150
TI  - Vector photorefractive spatial solitons.

PMID- 19862151
TI  - Measurement of index modulation along an optical fiber Bragg grating.

PMID- 19862152
TI  - Dramatically improved transmission of ultrashort solitons through 40 km of
      dispersion-decreasing fiber.

PMID- 19862153
TI  - Nondestructive waveguide loss-measurement method using self-pumped phase
      conjugation for optimum end-fire coupling.

PMID- 19862154
TI  - Compact 170-W continuous-wave diode-pumped Nd:YAG rod laser with a cusp-shaped
      reflector.

PMID- 19862155
TI  - Continuous-wave tunable light source at 1.6 mu m by difference-frequency mixing
      in CsTiOAsO4.

PMID- 19862156
TI  - 400-mW continuous-wave diode-pumped Cr:LiSAF laser based on a power-scalable
      concept.

PMID- 19862157
TI  - Group-velocity mismatch compensation in continuous-wave lasers mode locked by
      second-order nonlinearities.

PMID- 19862158
TI  - Spectral linewidth of a free-running continuous-wave single-frequency external
      cavity quantum-well InGaAs / AlGaAs diode laser.

PMID- 19862159
TI  - High-repetition-rate mode-locked Er-doped fiber lasers by harmonic injection
      locking.

PMID- 19862160
TI  - Period doubling and quasi-periodicity in additive-pulse mode-locked lasers.

PMID- 19862162
TI  - Inconsistency of the constant constraint criterion in optical correlation pattern
      recognition.

PMID- 19862161
TI  - Femtosecond pulse amplification in cladding-pumped fibers.

PMID- 19862163
TI  - Maximal limits on the information throughput of spatial light modulators.

PMID- 19862164
TI  - Optoelectronic implementation of a diffusion neural network for edge detection.

PMID- 19862165
TI  - Reversality of optical interactions in noncentrosymmetric media.

PMID- 19862166
TI  - Cross-talk noise in volume holographic memory with spherical reference beams.

PMID- 19862167
TI  - High-frequency enhancement of magneto-optic data storage signals by optical and
      electronic filtering.

PMID- 19862168
TI  - Passive signal processing for a miniature Fabry-Perot interferometric sensor with
      a multimode laser-diode source.

PMID- 19862169
TI  - Z-scan measurement technique for non-Gaussian beams and arbitrary sample
      thicknesses.

PMID- 19862170
TI  - Use of electronic speckle pattern interferometry for temperature distribution
      measurements through liquids.

PMID- 19862171
TI  - Three-pulse digital particle image velocimetry.

PMID- 19862173
TI  - Multilevel binary phase grating polarization device with a birefringent
      substrate.

PMID- 19862172
TI  - Gratings in the resonance domain as polarizing beam splitters.

PMID- 19862174
TI  - Splitting of high-Q Mie modes induced by light backscattering in silica
      microspheres.
AB  - We have observed that very high-Q Mie resonances in silica microspheres are split
      into doublets. This splitting is attributed to internal backscattering that
      couples the two degenerate whispering-gallery modes propagating in opposite
      directions along the sphere equator. We have studied this doublet structure by
      high-resolution spectroscopy. Time-decay measurements have also been performed
      and show a beat note corresponding to the coupling rate between the clockwise and
      counterclockwise modes. A simple model of coupled oscillators describes our data
      well, and the backscattering efficiency that we measure is consistent with what
      is observed in optical fibers.

PMID- 19862175
TI  - Radiation-mode coupling loss in tilted fiber phase gratings.
AB  - We demonstrate that grating tilt is an important adjustable parameter that can be
      utilized in addition to the more familiar parameters of grating length and index
      change to tune the spectral shapes of fiber phase gratings designed to perform
      demanding filter applications through guided-mode to radiation-mode coupling
      loss. A comparison is made between calculated transmission spectra obtained from
      a coupled-mode-theory analysis and measured spectra obtained from strong gratings
      written by ultraviolet irradiation of deuterium-sensitized fiber with grating
      tilt angles ranging from 0 degrees to 15 degrees . We show that good agreement is
      obtained between the experimental measurements and the theoretical predictions.

PMID- 19862177
TI  - Infrared solar glint clutter on the ocean surface.
AB  - A closed-form expression is developed for the infrared solar glint clutter
      radiance generated by the nearhorizon ocean surface. The clutter radiance is
      calculated as a function of water temperature, wind speed, wind direction, and
      solar position and agrees well with midwave infrared imagery measurements.

PMID- 19862176
TI  - Depth of focus and the moment expansion.
AB  - We introduce the so-called moment expansion of a defocused image as a tool for
      analyzing and improving the depth of focus in optical imaging. It is shown that a
      number of previously noted defocus phenomena can be readily derived or explained
      in terms of moment expansion. Some potential applications of the moment expansion
      to phase-shifting mask and pupil filter design for optical lithography are also
      briefly noted.

PMID- 19862178
TI  - Superluminal-source-induced emission.
AB  - Raman emission by an axicon-generated superluminal source is demonstrated. The
      anti-Stokes radiation is emitted at an angle defined by a Cerenkov-type
      condition. This technique of superluminal-source generation has advantages in
      both low pump self-phase modulation and compensation of temporal walk-off caused
      by group-velocity dispersion, rendering the scheme useful for efficient Raman
      conversion, pump-probe measurements, and harmonic and optical parametric
      generation with ultrashort intense pulses.

PMID- 19862179
TI  - Very-high-gain single-pass two-beam coupling in blue Rh:BaTiO(3).
AB  - Two-beam coupling has been studied at red and near-infrared wavelengths in blue
      Rh:BaTiO(3). High amplification, of the order of 20,000-37,000, of a weak signal
      beam has been measured. The effect of strong intensity-dependent transmission is
      considered when theoretical plots are fitted to the experimental data.

PMID- 19862180
TI  - Experimental evidence of modulation instability in a photorefractive
      Bi(12)TiO(20) crystal.
AB  - We present experimental results on the propagation of an interference pattern of
      two He-Ne laser beams of unequal amplitudes through a photorefractive
      Bi(12)TiO(20) crystal in the presence of drift nonlinearity. The phenomenon that
      we have observed is the focusing of the fringes as the nonlinearity of the
      crystal is increased. We show that such a phenomenon can be quantitatively
      interpreted in the framework of modulation instability theory.

PMID- 19862181
TI  - Suppression of the Gordon-Haus noise by a modulated Raman pump.
AB  - By launching a modulated Raman pump along with a soliton, we can reduce the
      random walk of solitons caused by the amplifier noise. The pump injected at one
      amplifier is filtered out at the next amplifier position. The group-velocity
      mismatch plays the role of a sliding frequency under properly chosen parameter
      space.

PMID- 19862182
TI  - Soliton transmission control by Butterworth filters.
AB  - Butterworth filters of second or higher order periodically inserted along a
      soliton transmission line, although they are flat at bandpass center, give to
      first order a nonzero restoring force for frequency and amplitude displacements.
      The amplified spontaneous emission generated at the filter center frequency is
      significantly less than that generated with fixed etalons for the same damping
      strength.

PMID- 19862183
TI  - Reduction of soliton interactions by zigzag-sliding-frequency guiding filters.
AB  - Reductions of the soliton interactions and jitter by the upsliding-frequency
      filter, the downsliding-frequency filter, and the zigzag-sliding-frequency filter
      are numerically studied. It is shown that the most effective filter for reducing
      the soliton interactions is the zigzag-sliding-frequency filter.

PMID- 19862184
TI  - Combined influence of amplifier noise and intrapulse Raman scattering on the bit
      rate limit of optical fiber communication systems.
AB  - Amplified spontaneous emission noise generates fluctuations in soliton energy and
      therefore fluctuations in the Raman self-frequency shift and in the group
      velocity. The corresponding timing jitter is found to be the main limitation for
      communication distances less than 1500 km.

PMID- 19862185
TI  - Polarization cross saturation in an Er(3+)-doped fiber ring laser.
AB  - The cross saturation between the polarization eigenmodes is measured in a
      unidirectional Er(3+) -doped fiber ring laser in which the population inversions
      for the polarization components are decoupled only by polarization hole burning.
      A coupling factor of beta = 0.80 +/- 0.01 is obtained from measurements of the
      polarization antiphase dynamics in the laser.

PMID- 19862186
TI  - Injection locking of a diode-pumped Nd:YAG laser at 946 nm.
AB  - Injection locking in the quasi-three-level laser system Nd:YAG (4)F(3/2)
      (4)I(9/2) at 946 nm is reported. The master and slave oscillators are pumped by
      laser diodes. The master oscillator is frequency stabilized to a high-finesse
      cavity, resulting in a laser linewidth of less than 10 Hz. Using intracavity
      frequency doubling of the slave oscillator, we achieve a single-mode output power
      of 60 mW at 473 nm. The laser radiation was frequency quadrupled, resulting in an
      UV power of 0.55 mW at 236.5 nm. The laser system was used to excite a strongly
      forbidden In(+) transition, proposed as a new optical frequency standard.

PMID- 19862187
TI  - Self-starting self-mode-locked femtosecond diode-pumped Cr:LiSAF laser.
AB  - We describe a diode-pumped Kerr-lens mode-locked Cr(3+):LiSrAlF(6) laser that
      produces 50 mW of 70-fs pulses in the 820-890-nm range when pumped by two red
      diodes of 400 mW each. By using a lower-transmission output coupler we have
      demonstrated for the first time to our knowledge a self-starting regime with an
      output power of 10 mW and 55-fs pulses.

PMID- 19862188
TI  - Noise reduction by harmonic injection locking of passively mode-locked erbium
      doped fiber lasers.
AB  - Harmonic injection locking can generate pulse trains at high repetition rates
      from passively mode-locked lasers. We have examined experimentally the mutual
      interaction of noise with the locking process. For injected signals with large
      timing and amplitude noise, the mode-locked fiber laser generated a pulse train
      with reduced noise. Injected signals with low timing and amplitude noise were
      employed for the reduction of the internal noise of the passively mode-locked
      laser. The achieved output pulse-to-pulse timing jitter in the range of 20-2500
      Hz was ~0.6 ps, comparable with that of actively stabilized fiber lasers.

PMID- 19862189
TI  - Femtosecond mid-infrared optical parametric oscillator based on CsTiOAsO(4).
AB  - A high-repetition-rate Ti:sapphire laser is used to synchronously pump a type-II
      angle-tuned CsTiOAsO(4) (CTA) optical parametric oscillator. When pumped at 809
      nm, the optical parametric oscillator is tunable from 1.007 to 1.180 microm in
      the signal branch and from 2.590 to 4.120 microm in the idler branch. Powers as
      high as 235 mW are obtained in the signal branch. Pulse widths as short as 56 fs
      are generated at 1.115 microm. CTA is shown to have a unique combination of low
      walk-off and low dispersion that contributes to its high gain and conversion
      efficiency.

PMID- 19862190
TI  - Phase-extraction algorithm in laser-diode phase-shifting interferometry.
AB  - A phase-shifting interferometer with a laser diode has been studied that is
      insensitive to the changes in laser power associated with variation in current.
      The tested phase is measured by six interferograms by a newly developed phase
      extraction algorithm. The phase is calculated from a least-squares fit to an
      interferogram. The systematic phase error that is due to the variation in laser
      output has been numerically investigated to have a periodicity of 2pi rad
      compared with the experimental result for the conventional phase-extraction
      algorithm. Good agreement between them is shown.

PMID- 19862191
TI  - Direct autocorrelation measurements of mid-infrared picosecond pulses by quantum
      well devices.
AB  - We report the direct autocorrelation of ultrashort mid-infrared laser pulses,
      using an unbiased GaAsy/GaAlAs quantum-well device as a nonlinear photovoltaic
      medium. Using this method, we autocorrelate ultrashort (3-ps) low-energy (~500
      nJ) pulses of 10.6-microm light. This approach should permit the autocorrelation
      of subpicosecond infrared pulses.

PMID- 19862192
TI  - Characterization of short-pulse oscillators by means of a high-dynamic-range
      autocorrelation measurement.
AB  - A high-dynamic-range autocorrelation technique was used to characterize the
      temporal pulse shape of ultrashort laser pulses produced from four separate
      oscillators. These lasers included two Kerr-lens mode-locked Ti:sapphire
      oscillators as well as a Nd:glass and a Ti:sapphire oscillator, each passively
      mode locked by an antiresonant Fabry-Perot semiconductor saturable absorber. It
      was shown that the Nd:glass oscillator supported a pulse that was temporally
      clean over 8 orders of magnitude.

PMID- 19862193
TI  - Experimental verification of soliton mode locking using only a slow saturable
      absorber.
AB  - We demonstrate experimentally that solid-state lasers with strong solitonlike
      pulse shaping can be mode locked by a slow saturable absorber only, i.e., the
      response time is much slower than the width of the soliton. A Ti:sapphire laser
      mode locked by a low-temperature-grown GaAs absorber with 10-ps recovery time
      generates pulses as short as 300 fs without the need for Kerr-lens mode locking
      and critical cavity alignment. An extrapolation of this result would predict that
      an asymptotically equal to 100-fs recovery time of a semiconductor absorber could
      support pulses into the 10-fs regime.

PMID- 19862194
TI  - Dammann-grating-based optodigital position converter.
AB  - An optodigital position converter based on a Dammann grating is proposed. The
      converter is based on a diffraction grating with a high diffraction efficiency
      coupled with a binary encoding mask. The module permits parallel processing of a
      scene so that one can extract the position of a correlation peak. Compression of
      the information is also performed. The binary output is compatible with digital
      systems.

PMID- 19862195
TI  - Autocorrelation central hole estimates in nonlinear photon-counting detectors.
AB  - In an experiment in which two or more photoevents arriving at the same pixel are
      considered a single count, a one-pixel-size central hole appears in the
      autocorrelation estimate. This hole is a source of error when high-resolution
      techniques based on the autocorrelation function are applied to image or signal
      recovery. We present an experimental method to evaluate the autocorrelation
      central hole based on the nonlinear behavior of the total number of counts per
      frame when clipped photocount distributions are considered. The technique is easy
      to perform and provides high accuracy.

PMID- 19862196
TI  - Optical folding-flash analog-to-digital converter with analog encoding.
AB  - We describe an optically assisted folding-flash analog-to-digital converter. The
      periodic transfer function of the Mach-Zehnder interferometer is used to perform
      analog folding on the electronic signal to be quantized. A novel analog encoding
      scheme for efficient generation of gray code digital data is proposed. The new
      encoding scheme eliminates the requirement for interferometers with ultralow
      V(pi), which, so far, has hindered the development of such systems. The encoding
      concept is experimentally demonstrated through the use of LiNbO(3) modulators.

PMID- 19862197
TI  - Fast reconfigurable optical image switching/routing system.
AB  - A novel system that is capable of switching/routing two-dimensional images in
      arbitrary configurations is described. The switching network can be reconfigured
      in a few microseconds with high light efficiency.

PMID- 19862198
TI  - Fringe formation and coherence of a soft-x-ray laser beam illuminating a Mach
      Zehnder interferometer.
AB  - We investigated the fringe visibility produced by a Mach-Zehnder interferometer
      illuminated by a collisionally pumped yttrium x-ray laser operating at 15.5 nm.
      Fringe visibility varied as a function both of relative path delay and of
      relative spatial overlap of the beams. This visibility information was extracted
      quantitatively from several interferograms and analyzed to produce a
      characterization of the temporal coherence, yielding a gain-narrowed linewidth of
      1.3 pm for the 15.5-nm laser transition and spatial coherence consistent with an
      effective source size of approximately 220 microm +/- 50% at the x-ray laser
      output.

PMID- 19862199
TI  - Nonperturbative analytical solution for steady-state photorefractive recording.
AB  - A nonperturbative analytical solution for steady-state photorefractive recording
      in the diffusion approximation has been obtained. It applies to any arbitrary
      modulation depth m and includes, as limit cases, the perturbation solutions
      reported by previous authors.

PMID- 19862200
TI  - Experimental characterization of an angle-multiplexed holographic memory.
AB  - We demonstrate a simple angle-multiplexing holographic storage system, using a
      single acousto-optic deflector to achieve fast random access to the stored
      holograms. We used this system to store as many as 300 holograms in a 90 degrees 
      geometry Fe:LiNbO(3) crystal. To characterize the system performance, we analyzed
      the reconstructions in terms of the signal-to-noise ratio.

PMID- 19862201
TI  - Coded-wavelength multiplex volume holography.
AB  - We introduce the technique of coded-wavelength multiplex holography. We encode
      each wavelength with a discrete angular spectrum of plane waves, so that the
      total number of multiplexed holographic pages equals the number of wavelengths
      multiplied by the number of discrete wave vectors at each wavelength. Encoding
      with different propagation angles further permits one to utilize the properties
      of grating degeneracy to assemble an image from a mosaic of smaller images and to
      multiplex such images at different wavelengths.

PMID- 19862202
TI  - Simultaneous recovery of strain and temperature fields by the use of two-moded
      polarimetry with an in-line mode splitter/analyzer.
AB  - We report the simultaneous recovery of temperature and strain through measurement
      of polarization changes in the LP(01) and LP(11) modes of Andrew Corporation
      elliptical-core fiber. This technique required the development of an in-line mode
      splittery/analyzer, which is also described. The scheme has been demonstrated to
      be sensitive to changes of 1 degrees C and 5 microepsilon and is compatible with
      white-light multiplexing methods to provide quasidistributed information.

PMID- 19862203
TI  - Fiber-optic atmospheric turbulence sensor.
AB  - A novel dual-air-gap fiber-optic Mach - Zehnder interferometer is proposed for
      the direct measurement of the atmospheric optical turbulence structure constant
      C(n)(2). The shot-noise-limited minimum detectable structure constant is
      estimated to be 4.5 x 10(-20) m(-2/3), which is more than 2 orders of magnitude
      below a typical value of 10(-17) m(-2/3) for weak turbulence. This sensor is
      suitable for the measurement of atmospheric turbulence over land and ocean
      surfaces.

PMID- 19862204
TI  - Near-field optical microscope based on local perturbation of a diffraction spot.

PMID- 19862205
TI  - Postfabrication exposure of gap-type bandpass filters in broadly chirped fiber
      gratings.
AB  - High efficiency in-fiber bandpass filters with arbitrary passband/stop-band
      combinations have been produced successfully with an UV postfabrication exposure
      technique in broadly chirped fiber gratings. By further concatenating such a
      bandpass filter with two additional chirped gratings we achieved a finesse as
      high as 220 for a 36-nm stop band. This new approach exhibits great advantages in
      controlling precisely the profiles of bandpass filters in terms of stop-band
      width, transmission wavelength and linewidth, and spacing of passbands.

PMID- 19862206
TI  - Two-photon absorption and optical-limiting properties of novel organic compounds:
      erratum.

PMID- 19862207
TI  - Optical trapping of low-refractive-index microfabricated objects using radiation
      pressure exerted on their inner walls.
AB  - Optical trapping of transparent ring-shaped micrometer-sized objects with a
      refractive index lower than that of the surrounding medium has been demonstrated
      by use of a strongly focused TEM(00)-mode laser beam. Axial trapping of these
      objects is a result of the upward radiation pressure induced when the incident
      light strikes the inner wall and transmitted light leaves from the bottom.
      Transverse trapping of these objects occurs because the total repulsive radiation
      pressure exerted on the inner wall of the object is directed toward the laser
      beam axis. Three-dimensional manipulation of f luorinated polyimide micro-objects
      (refractive index n(1)= 1.525, outer diameter 10 microm, inner diameter 5 microm,
      and thickness 5.7 microm) in a high-refractive-index liquid (n(2)= 1.605) was
      experimentally shown to be possible by use of an objective lens with a wide range
      of numerical apertures from 1.25 to 0.5.

PMID- 19862208
TI  - Scattering of light by large nonspherical particles: ray-tracing approximation
      versus T-matrix method.
AB  - We report, for the f irst time to our knowledge, comparisons of light-scattering
      computations for large, randomly oriented, moderately absorbing spheroids based
      on the geometric-optics approximation and the exact T-matrix method. We show that
      in most cases the geometric-optics approximation is (much) more accurate for
      spheroids than for surface-equivalent spheres and can be used in phase function
      computations (but not in polarization computations) for nonspherical particles
      with size parameters as small as 60. Differences in the single-scattering albedo
      between geometric-optics and T-matrix results are surprisingly small, even for
      small size parameters.

PMID- 19862209
TI  - Fermat photons in turbid media: an exact analytic solution for most favorable
      paths-a step toward optical tomography.
AB  - Photon propagation in a turbid medium characterized by highly forward-directed
      light scattering can be described by a generalized Fermat principle, a
      counterpart of the conventional Fermat principle for transparent media. An exact
      analytic solution for the most favorable photon paths (Fermat paths) has been
      found and is investigated. An analysis intended to encourage and facilitate
      experimental observation of Fermat photons is presented. The feasibility of using
      the theory in time-resolved optical tomography for the recognition of objects
      hidden in turbid media is discussed.

PMID- 19862210
TI  - Wave-front reconstruction with a Fourier hologram in a phase-conjugating mirror
      oscillator.
AB  - A laser profile consisting of 113 coupled Gaussian waves is obtained in a cw
      oscillator by use of a BaTiO(3) crystal as both an amplifying medium and a phase
      conjugating mirror. Mutual locking of Gaussian waves is performed by a pair of
      spatial f ilters. One of them is a high-resolution holographic component; the
      other is an opaque screen with identical circular apertures.

PMID- 19862211
TI  - Mirrors with point-spread functions that exhibit wavelet-related characteristics.
AB  - Mirrors with amplitude point-spread functions that exhibit wavelet-related
      characteristics are profiled by the method of stationary points and the method of
      Fresnel zones. The unknown optical path function phi(r) of the diffraction
      integral is reconstructed from its stationary points, which are identif ied from
      locations where the pupil function of the optical system is an extremum. The
      phi(r) that describes the paths taken by the light from the point source to the
      observation plane via the ref lecting surface is used as a constraint in the
      procedure. In particular, circular distributions of the Mexican-hat wavelet and
      the Fourier transform of the Haar wavelet are considered for the point-spread
      functions.

PMID- 19862212
TI  - Characterization of KNbO(3) crystal for frequency doubling of a tunable pulsed
      near-infrared laser.
AB  - Using KNbO(3) crystals for second-harmonic generation in the blue spectral range,
      we have obtained conversion efficiencies as high as 53.7%. To our knowledge this
      value is the highest reported for a pulsed laser. A gainswitched nanosecond
      Ti:sapphire oscillator, amplified by a Cr:LiSrAlF(6) multipass amplifier, was
      used as the fundamental light source. The maximum energy obtained at the harmonic
      wavelength of 430 nm was 38 mJ for a bandwidth of 230 MHz.

PMID- 19862213
TI  - Observation of mutual trapping and dragging of two-dimensional spatial solitary
      waves in a quadratic medium.
AB  - We report experimental evidence for trapping of two-dimensional (2 + 1) spatial
      solitary waves in a KTP crystal resulting from its second-order nonlinearity. In
      addition, dragging of the solitary beams is observed as a function of fundamental
      input intensity and of the relative phase difference between the fundamental and
      the second harmonic when beams at both frequencies are coherently launched.

PMID- 19862214
TI  - Beam steering by chi((2)) trapping.
AB  - We show numerically the mutual dragging and locking together of intense
      fundamental and second-harmonic light beams propagating in second-order nonlinear
      media, and we discuss the potential applications of such effects for the steering
      of beams by spatial phase modulation of the input signals.

PMID- 19862215
TI  - Light-induced noncentrosymmetry in acceptor-donor-substituted azobenzene
      solutions.
AB  - Light-induced noncentrosymmetry was achieved experimentally in acceptor-donor
      substituted azobenzene solutions and observed by phase-matched nondegenerate six
      wave mixing. The microscopic origin of the induced noncentrosymmetry was found to
      be orientational hole burning, which was distinguished directly with net
      orientation of molecules by experimental observations. The decay time of the
      induced noncentrosymmetry depended on the rotational orientation time of the
      sample's molecule, which varied linearly with the viscosity of the solvent.

PMID- 19862216
TI  - Laser-induced breakdown versus self-focusing for focused picosecond pulses in
      water.
AB  - We present numerical studies of nonlinear propagation for picosecond pulses
      focused in water. Depending on the pulse duration and focusing conditions, for
      some input powers self-focusing may precede laser-induced breakdown and vice
      versa. We derive a criterion that predicts the relative roles of laser-induced
      breakdown and self-focusing.

PMID- 19862217
TI  - Optical solitons supported by competing nonlinearities.
AB  - It is demonstrated that optical solitons can propagate in a dispersive (or
      diffractive) medium with competing quadratic [i.e., chi((2))] and cubic [i.e.,
      chi((3))] nonlinearities. Strong interplay between the nonlinearities leads to
      novel effects, in particular the following: (i) stable bright solitons can still
      exist in a self-defocusing (owing to cubic nonlinearity) medium supported by
      quadratic parametric interactions and (ii) chi((2)) nonlinearity can lead to
      instabilities of chi((3)) solitons.

PMID- 19862218
TI  - Data-dependent timing jitter in wavelength-division-multiplexing soliton systems.
AB  - Soliton timing jitter that is due to amplifier noise has been studied
      extensively. In wavelength-multiplexed soliton systems jitter also results from
      collisions between solitons on different channels. We derive an expression for
      the variance in pulse arrival times because of such collisions and predict system
      performance using this result. Jitter depends not only on perturbations to the
      fiber but also on the encoding of information. When the expression is applied to
      a system with loss and amplification, it is shown that extensive wavelength
      multiplexing may significantly enhance soliton communication systems.

PMID- 19862219
TI  - Soliton polarization self-orientation.

PMID- 19862220
TI  - Soliton interaction and bound states in amplified-damped fiber systems.
AB  - It is shown that the soliton interaction can be signif icantly reduced in a
      system with ultimately stable soliton propagation. Moreover, under the action of
      strong filtering and nonlinear gain the soliton interaction can change sign from
      attraction to repulsion and vice versa. The formation of in-phase and out-of
      phase bound states is also demonstrated.

PMID- 19862221
TI  - Perturbation model for computing optical fiber birefringence from a two
      dimensional refractive-index profile.
AB  - A vector perturbation model for computing optical fiber birefringence for an
      arbitrary two-dimensional index profile is developed. The vector wave equation is
      solved to yield the unperturbed vector f ields for an azimuthally symmetric
      refractive index. These f ields are used as the basis for the degenerate
      perturbation analysis. Unlike with the scalar perturbation theory, only f irst
      order perturbation analysis suff ices for the computation of birefringence.
      Computed birefringence for various perturbations are reported.

PMID- 19862222
TI  - Photoinduced Bragg gratings in As(2)S(3) optical fibers.
AB  - Bragg gratings have been fabricated in As(2)S(3) optical fibers through the
      photoinduced refractive-index change process. Bragg filters in the fiber show a
      more-ideal response than those fabricated in the corresponding bulk material.
      Some features characteristic of chalcogenide fibers and Ge-doped oxide fibers are
      discussed comparatively.

PMID- 19862223
TI  - Soliton stabilization in long-distance fiber transmissions with semiconductor
      amplifiers.
AB  - By perturbation theory and simulations I analyze the stability of optical
      solitons that propagate in a periodically amplif ied fiber link with lumped
      semiconductor amplifiers, bandpass f ilters, and acousto-optic frequency
      shifters. I obtain the conditions for suppressing the effects of semiconductor
      gain and index saturation.

PMID- 19862224
TI  - Strong photosensitive gratings in tin-doped phosphosilicate optical fibers.
AB  - Strong photosensitive gratings of both type I and II have been demonstrated in
      germanium-free tin-doped phosphosilicate fibers. An index change of ~1.2 x 10(-3)
      has been achieved in 40 s of exposure. The fibers have strong absorption (~0.8
      dB/microm) at the writing wavelength of ~248 nm because of tin doping. This is
      the f irst time to our knowledge that such strong gratings have been written in a
      phosphorous-containing silica fiber without low-temperature hydrogenation and
      that type II gratings have been written in a germanium-free fiber. The tin-doping
      technique can be used to write gratings in rare-earth-doped phosphosilicate
      fibers and to produce low-N.A. fibers for mass production of strong single-pulse
      type II gratings during fiber pulling.

PMID- 19862225
TI  - Integrated electro-optic Q switching in a domain-inverted Nd:LiTaO(3) laser.
AB  - We report a novel integrated Q-switched laser constructed from a bulk domain
      inverted single Nd:LiTaO(3) crystal that combines the laser gain and the electro
      optic effect. The Q of the cavity is controlled electro-optically by exploitation
      of the deflection that occurs at the boundary of two oppositely directed domains
      under the application of an electric field. The integrated Q-switching element,
      with dimensions of 4.1 mm x 4.6 mm x 1 mm, generates 22-ns pulses at 1.08 microm
      with a peak power of 64 W and an operating voltage of ~600 V. The output is seen
      to be completely free from prelasing or afterpulsing.

PMID- 19862226
TI  - Single-mode continuous-wave Cr(3+):LiSAF ring laser pumped by an injection-locked
      670-nm broad-area diode laser.
AB  - We report on an efficient continuous-wave Cr(3+):LiSrAlF(6) ring laser pumped by
      the near-diffraction-limited output of an injection-locked 665-nm broad-area
      diode laser. With an absorbed pump power of 120 mW the ring laser generates 22 mW
      of single-mode 855-nm radiation with a spectral linewidth of less than 10 MHz.
      Unidirectional operation and longitudinal-mode control of this ring laser is
      achieved by injection of 855-nm diode-laser radiation into the ring cavity.
      Optical feedback of ring-laser radiation into the diode laser narrows the diode
      laser's linewidth and locks its frequency to a resonance of the ring resonator.

PMID- 19862227
TI  - Tunable picosecond infrared laser system based on parametric amplification in KTP
      with a Ti:sapphire amplifier.
AB  - A picosecond laser system that will generate high-power tunable IR pulses with
      bandwidths suitable for spectroscopic applications is discussed. The system is
      based on white-light continuum generation in ethylene glycol and optical
      parametric amplification in potassium titanyl phosphate. The nonlinear-optical
      processes are driven by a regeneratively amplified Ti:sapphire laser that
      produces 1.7-ps pulses at a repetition rate of 1 kHz. Energies as high as 40 and
      12 microJ have been achieved over the signal (1.02-1.16-microm) and idler (2.6
      3.7-microm) tuning ranges, respectively. The IR beam temporal and spatial
      characteristics are also presented.

PMID- 19862228
TI  - Femtosecond-pulse-driven electron-excited extreme-ultraviolet lasers in Be-like
      ions.
AB  - A suggestion for the generation of extreme-ultraviolet (XUV) laser radiation
      based on tunneling ionization and subsequent electron excitation of Deltan not
      equal 0 transitions is described. The favorable scaling of the required intensity
      of the pump laser with the output XUV wavelength is compared with that exhibited
      by XUV lasers ased on Deltan = 0 transitions. Calculations for Be-like Ne predict
      signif icant gain at 14.1 nm.

PMID- 19862229
TI  - Optical second-harmonic generation as a probe of electric-field-induced
      perturbation of centrosymmetric media.
AB  - Polarization-selective optical second-harmonic generation (SHG) is applied to
      monitor nonuniform polarization distributions in centrosymmetric media modulated
      by an external dc electric field. Two different systems are investigated: first,
      optical SHG from a Au-Si(100) Schottky Barrier is shown to be a direct probe of
      the electric field polarity near such a metal-semiconductor interface. Second, a
      poled polymer exhibits a strong anisotropic SHG signal under normal incidence,
      indicating a nonuniform field enhancement at the edges of the poling electrode.
      The results demonstrate the sensitivity of SHG to small symmetry perturbations.
      Consequences for device applications are discussed.

PMID- 19862230
TI  - Ti:sapphire amplifier producing millijoule-level, 21-fs pulses at 1 kHz.
AB  - We have developed a Ti:sapphire amplifier system capable of producing pulses of 1
      mJ, with 20-22-fs pulse duration, at a 1-kHz repetition rate. The amplifier has a
      unique design consisting of a three-mirror multipass ring configuration with a
      highly doped Ti:sapphire crystal as the gain medium. Pulses of 15-fs duration
      from a Ti:sapphire oscillator are temporally stretched and injected into the
      amplifier, which is an eight-pass system with a total gain of 10(6). The amplif
      ier is more than 10% efficient, and the shot-to-shot energy fluctuation of the
      output is less than 2%. The output beam focuses to 1.8 times the diffraction
      limit.

PMID- 19862231
TI  - Tunable femtosecond-pulse generation by an optical parametric oscillator in the
      saturation regime.
AB  - We demonstrate the generation of powerful, bandwidth-limited pulses in a KTP
      optical parametric oscillator synchronously excited by the pulse train of a f
      lash-lamp-pumped, mode-locked Nd:YLF laser. Operating the optical parametric
      oscillator a factor of 4 above threshold and optimizing the cavity length yields
      pulses of 260 +/- 30 fs. The shortening by a factor of 15 relative to the pump is
      accompanied by extended pulse wings. Tunability of the device is shown in the
      wavelength range 1.2 -1.6 microm.

PMID- 19862232
TI  - Control of the spectral-oscillation artifact in femtosecond pump-probe
      spectroscopy.
AB  - We present time-resolved pump-probe experiments on a semiconductor in which the
      signal shape, dominated by perturbed free polarization decay, is strongly
      dependent on the probe pulse's spectral shape. This effect can be used
      efficiently to reduce large spectral oscillations that prevent the observation of
      weak signals near a narrow spectral structure.

PMID- 19862233
TI  - Self-induced modulational-instability laser.
AB  - We analyze the transition from passive mode locking into the novel modulational
      instability regime of erbiumdoped fiber lasers. By including in the cavity an
      anisotropic loss, we observed, depending on the polarization setting, the
      generation of either single pulses as short as 435 fs or a continuous-wave train
      of 3.5-ps-long solitons at a repetition rate of 76 GHz. Even with no anisotropic
      losses in the cavity, soliton trains at a repetition rate of as high as 130 GHz
      were still observed. We believe that this is the first observation of a self
      induced modulational-instability laser.

PMID- 19862234
TI  - A foundation for logarithmic measures of fluctuating intensity in pattern
      recognition.
AB  - Independent analyses using Fisher information, optimal filtering, and information
      theory show that matched filtering images with hypothetical patterns in the
      logarithmic domain provides an optimal method for pattern recognition in the
      presence of signal-dependent noise arising from complex Gaussian fluctuations in
      the received fields. This provides a mathematical justification for the use of
      logarithmic units (i.e., decibels) in a variety of engineering applications.

PMID- 19862235
TI  - Matched filtering incorporating colored-noise compensation for joint transform
      correlators.
AB  - Optimal recognition of patterns with respect to noise tolerance is obtained when
      matched filtering is applied with colored-noise compensation, for which input
      noise spectral characteristics have to be known in advance. Conventional joint
      transform correlator systems provide such optimality only when the input noise is
      white. We propose general means to facilitate colored-noise tolerance by
      incorporating either a priori or adaptive noise compensation in joint transform
      correlator-based matched filtering schemes. Adaptive compensation for colored
      noise may be achieved in real-time operation by estimation of the noise power
      spectral density distribution from input power spectra information.

PMID- 19862236
TI  - Amplitude squeezing with a Fabry-Perot semiconductor laser: existence of an
      optimum biasing condition.
AB  - The effect of gain suppression on amplitude squeezing with a Fabry-Perot
      semiconductor laser is studied with a semiclassical model. A strong decrease of
      the internal amplitude noise and an optimum biasing point with minimum amplitude
      noise are demonstrated. Small gain nonlinearities improve external compression.

PMID- 19862237
TI  - Self-calibrating quantum efficiency measurement technique and application to
      Pr(3+)-doped sulfide glass.
AB  - A measurement technique is described in which the radiative quantum efficiency of
      certain transitions in rare-earth-doped glasses can be determined based only on
      relative fluorescence measurements. We calibrate the emission from the level of
      interest by measuring emission into that level from a higher excited level.
      Application of the technique to Pr(3+)-doped sulfide glasses yields quantum
      efficiencies for the (1)G(4) ? (3)H(5) transition as high as 60%, in good
      agreement with measurements using the integrating sphere technique. Calculated
      efficiency values based on the Judd-Ofelt technique are shown to be subject to
      inherent uncertainties.

PMID- 19862238
TI  - Optical frequency measurement of the H(12)C(14)N Lamb-dip-stabilized 1.5-microm
      diode laser.
AB  - We have measured the frequency of the P(27) line of H(12)C(14)N at 1556 nm, using
      the 778-nm two-photon transition of Rb as a frequency reference. The measured
      frequency was 192, 622, 446.9 +/- 0.1 MHz. We believe that this experiment is the
      first absolute frequency measurement of a laser stabilized to a saturation dip at
      1.5 microm and also the most accurate measurement of a 1.5-microm optical
      frequency.

PMID- 19862239
TI  - Phase-compensated holographic recording based on anisotropic photorefractive
      diffraction.
AB  - We report a simple actively stabilized setup for holographic recording on
      sillenite photorefractive crystals that is based on the anisotropic diffraction
      properties of these materials. The method is much simpler than previously
      published ones, requires neither phase modulation nor synchronous phase-sensitive
      detection, and needs no external reference. We describe the successful operation
      of this stabilization procedure for a Bi(12)TiO(20) crystal in a practical
      holographic interferometry setup, using the 632.8-nm wavelength of a He-Ne laser.

PMID- 19862240
TI  - Volume holographic phase-retardation elements.
AB  - The form birefringence of subwavelength period gratings can be applied to realize
      phase-retardation elements. Previous researchers used high-frequency surface
      relief structures or sinusoidal gratings formed in photoresist to fabricate phase
      retardation elements. We present the performance of a volume holographic quarter
      wave phase-retardation element formed in a dichromated gelatin emulsion for
      operation at 632.8 nm. To our knowledge this is the first demonstration of a
      retardation element exhibiting this magnitude of phase delay in a volume
      material. The phase properties of volume gratings are investigated by both
      effective medium theory and rigorous coupled-wave analysis.

PMID- 19862241
TI  - Optical bit-rate conversion and bit-stream time reversal by the use of swept
      carrier frequency-selective optical data storage techniques.
AB  - We have demonstrated real-time all-optical bit-rate conversion and bit-sequence
      time reversal, using a variation of the swept-carrier frequency-selective optical
      storage/retrieval process. Working in the Mbit/s regime, we obtained order-of
      magnitude bit-rate enhancements and reductions. Output signals appear in a time
      forward or time-reversed format after an adjustable buffering storage time.
      Analysis of the method of its potential indicates applicability at substantially
      higher data rates.

PMID- 19862242
TI  - Detection of methyl radicals in a flat flame by degenerate four-wave mixing.
AB  - We report the spatially resolved detection of methyl radicals in a methane-air
      flat flame, using degenerate four-wave mixing (DFWM). A frequency-tripled dye
      laser pumped with a frequency-doubled Nd:YAG laser was used to access the
      Herzberg beta(1) band of methyl near 216 nm. Using a nearly phase-conjugate
      geometry, we detected methyl with high spatial resolution [0.2 mm (0.3 mm)
      vertical (horizontal) and ~6 mm longitudinal] and with good signal-to-noise ratio
      in a rich (o = 1.55) flame. Compared with laser absorption spectra, DFWM spectra
      were much less influenced by a broad featureless background. From the absorption
      data, we measured the peak methyl concentration to be 650 parts in 10(6),
      resulting in an estimated DFWM detection limit of 65 parts in 10(6).

PMID- 19862243
TI  - Coupled-mode equations for periodic superstructure Bragg gratings.
AB  - Periodic superstructure Bragg gratings are gratings in which the parameters vary
      periodically. Although one can determine their properties by using the standard
      coupled-mode equations for the electric field envelopes, it is shown that the
      analysis is simplified if one considers the super envelopes, i.e., the envelopes
      of the usual envelope functions. These super envelopes satisfy a set of (super)
      coupled-mode equations, which are formally identical to the standard coupled-mode
      equations for a uniform grating. This shows that, within certain frequency
      ranges, any superstructure Bragg grating acts approximately as a uniform grating.

PMID- 19862244
TI  - Snake beam: a paraxial arbitrary focal line.
AB  - The creation of paraxial arbitrary focal lines by a Fourier computer-generated
      hologram is demonstrated. The desired focal line is represented by a series of
      connected straight line segments, each of which is implemented by a radial
      harmonic function located on a different radial portion of the entire hologram.
      Each subhologram is multiplied by appropriate linear and quadratic phase
      functions and is shifted by some distance from the center. The two phase factors
      determine the location of each line segment, while the in-plane shift determines
      the tilt angle of the segment.

PMID- 19862245
TI  - Complex wave-field reconstruction by means of the Page distribution function.
AB  - The complex amplitude function in the waist of a one-dimensional Hermite-Gaussian
      model beam is measured by a noniterative method based on the Page distribution
      function in the two-dimensional spatial-angular phase space. The measurement
      procedure is realized by an extension of the knife-edge method. The model beam is
      generated by means of a phase plate in conjunction with a He-Ne laser.

PMID- 19862246
TI  - Ball lens reflections by direct solution of Maxwell's equations.
AB  - We calculate ball lens reflections, using the exact solution of Maxwell's
      equations for the scattering of a beam from a dielectric sphere. Our results are
      consistent to within 1 dB with measurements of backreflection to a single-mode
      fiber. We also calculate backreflection to an astigmatic spot laser diode.

PMID- 19862247
TI  - Complex grating structures with uniform phase masks based on the moving fiber
      scanning beam technique.
AB  - We present experimental results of complex grating structures fabricated with
      uniform phase masks by the moving fiber-scanning beam approach. Pure apodized
      gratings with side-mode-suppression levels in excess of 40 dB, self-apodized
      linearly chirped gratings, and phase shifted gratings with narrow-band
      transmission peaks have all been realized.

PMID- 19862248
TI  - Two-photon-induced fluorescence of biological markers based on optical fibers.
AB  - Optical fibers were used to induce fluorescence by means of two-photon absorption
      in fluorophores. The effect, studied in a solution of 4',6-diamidino-2
      phenylindole, demonstrated that a single-mode fiber is a more efficient two
      photon excitation source than a multimode fiber. This was shown with three
      different fibers.

PMID- 19862249
TI  - Efficient generation of mid-infrared radiation in an AgGa(x)In(1-x)Se(2) crystal.
AB  - Efficient generation of mid-infrared radiation by noncritically phase-matched
      second-harmonic generation is demonstrated in a mixed chalcopyrite crystal,
      AgGa(x)In(1-x)Se(2), and compared with that in an AgGaSe(2) crystal. Nonlinear
      coeff icients d(36) of AgGa(x)In(1-x)Se(2) and AgGaSe(2) crystals have also been
      derived.

PMID- 19862250
TI  - Polarization scattering by soliton-soliton collisions.
AB  - We have discovered experimentally that soliton-soliton collisions in wavelength
      division multiplexing significantly alter the polarization states of the
      colliding solitons. Analysis shows that the change in polarization is according
      to the cross product of the Stokes vectors of the colliding solitons.
      Birefringence of the fiber spans can turn this polarization scattering into a
      significant source of timing jitter.

PMID- 19862251
TI  - Time-dependent second-harmonic generation from the Si-SiO(2) interface induced by
      charge transfer.
AB  - We have observed that the second-harmonic signal generated from oxidized Si(001)
      varies on a time scale of several seconds in experiments involving a fundamental
      beam of lambda = 770 nm, 110-fs pulses at 76 MHz. We suggest that the temporal
      behavior arises from absorption of weak (<100-fW average power) third-harmonic
      light generated in air or in the sample, inducing charge transfer across the Si
      SiO(2) interface and trapping in the oxide layer. Detrapping has been determined
      to take several minutes.

PMID- 19862252
TI  - Waveguides formed by quasi-steady-state photorefractive spatial solitons.
AB  - We show that a quasi-steady-state photorefractive spatial soliton forms a
      waveguide structure in the bulk of a photorefractive material. Although the
      optically induced waveguide is formed by a very low-power (microwatts) soliton
      beam, it can guide a powerful (watt) beam of a longer wavelength at which the
      medium is nonphotosensitive. Furthermore, the waveguide survives, either in the
      dark or when guiding the longerwavelength beam, for a long time after the soliton
      beam is turned off. We take advantage of the solitons' property of evolution from
      a relatively broad input beam into a narrow channel and show that the soliton
      induces a tapered waveguide (an optical funnel) that improves the coupling
      efficiency of light into the waveguiding structure.

PMID- 19862253
TI  - Weak-beam trapping by bright spatial solitons in AlGaAs planar waveguides.
AB  - We demonstrate experimentally the trapping and spatial wave breaking of weak
      signal beams by orthogonally polarized bright spatial solitons. Experiments were
      performed in an AlGaAs planar waveguide excited at a wavelength of 1.55 microm.

PMID- 19862254
TI  - Generation of vibrational and rotational emissions by four-wave Raman mixing
      using an ultraviolet femtosecond pump beam.
AB  - A femtosecond KrF excimer laser is focused into molecular hydrogen to generate a
      multifrequency laser beam, consisting of many vibrational and rotational lines,
      in a transient Raman regime. The intensity distribution is unchanged from 5 to 13
      atm, in contrast to the case of nanosecond laser pump. The efficiency for
      generation of the rotational lines is improved by increasing the peak power,
      especially at longer wavelengths, indicating power-dependent and wavelength
      dependent behavior of this effect, as expected from theory.

PMID- 19862255
TI  - Photorefractive surface waves.
AB  - A laser beam propagating in a photorefractive crystal generates a refractive
      index profile that deflects the beam to one side. This nonlinear deflection can
      be balanced by total internal reflection at the crystal surface to produce self
      induced photorefractive surface waves. Theoretical and experimental evidence for
      this effect is given.

PMID- 19862256
TI  - Infrared hollow glass waveguides fabricated by chemical vapor deposition.
AB  - Hollow glass waveguides have been fabricated for the delivery of infrared
      radiation by chemical vapor deposition methods. A molybdenum film is first
      deposited inside 700-microm silica tubing by the hydrogen reduction of molybdenum
      chloride. Then a zinc sulfide or aluminum oxide film is deposited onto the
      molybdenum layer. These dielectric films enhance the reflectivity, and we observe
      a reduction in loss for the thin-film combination compared with the molybdenum
      film alone. The chemical vapor deposition techniques may be extended to the
      fabrication of hollow guides with multiple dielectric layers that have much lower
      losses than current single-layer designs.

PMID- 19862257
TI  - Equivalent refractive index of multiple-quantum-well waveguides by variational
      analysis.
AB  - We propose a new semianalytical method using variational analysis for developing
      an equivalent three-layer model of a multiple-quantum-well waveguide. Waveguiding
      properties such as effective index and field distribution of this equivalent
      waveguide are compared with those of previously reported equivalents and with the
      results obtained from the exact multilayer analysis of the multiple-quantum-well
      waveguide. The waveguiding properties are accurately predicted by this method,
      and the computational effort is significantly reduced.

PMID- 19862258
TI  - Characterization of planar antiresonant reflecting optical waveguide structures
      on silicon by an Abbe refractometer.
AB  - A method is reported for characterizing planar antiresonant reflecting optical
      waveguides (ARROW's) by use of an unmodified Abbe refractometer. The technique
      permits the simultaneous determination of the TE-mode effective indices of the
      allowable modes, the thickness and refractive index of the waveguide core.
      Results from experimental measurements of an ARROW waveguide compare well with
      those predicted by a f ield transfer matrix analysis.

PMID- 19862259
TI  - Highly efficient single-longitudinal-mode beta-BaB(2)O(4) optical parametric
      oscillator with a new cavity design.
AB  - A new coupled-cavity design for single-longitudinal-mode operation of an optical
      parametric oscillator (OPO) is presented. The OPO is based on a beta-BaB(2)O(4)
      crystal and is pumped by the third harmonic of a Nd:YAG laser. With this design,
      we achieved single-longitudinal-mode operation of the OPO with a decrease in the
      threshold and an increase in external efficiency compared with those of a
      conventional grazing-incidence OPO. A mathematical model that describes the mode
      spacings for this cavity is given.

PMID- 19862260
TI  - Nonlinear outcoupling mechanism in a cylindrical dielectric microcavity
      supporting stimulated Raman scattering.
AB  - We describe a previously unreported nonlinear scattering effect that occurs in
      cylindrical liquid jets irradiated by an intense laser pulse. The spatial
      characteristics of this feature are quite striking: light emanating from a thin
      (</=5 microm) circumferential ring near the cylinder surface. This ring can,
      depending on the pump intensity, be continuous or periodic in o. We have observed
      rings in several liquids (ethanol, water, and carbon disulfide) and, for the case
      of ethanol, in cylinders ranging from ~14 to ~76 microm in radius. We conclude
      that the rings are composed of plasma generated by the intense stimulated Raman
      scattering fields in the cylinder.

PMID- 19862261
TI  - Polymer microdisk and microring lasers.
AB  - Dye-doped polymer microlasers have been fabricated by photolithography and self
      assembly. Microdisk lasers 5 to 30 microm in diameter were photolithographically
      patterned on thin planar polymer waveguides. We formed polymer microring lasers
      on thinned silica fibers by dipping the fibers in polymers and allowing the
      polymer droplets to cure.

PMID- 19862262
TI  - Continuous-wave operation of saturable-gain degenerate four-wave mixing in a
      Nd:YVO(4) amplifier.
AB  - We experimentally demonstrate for the first time to our knowledge continuous-wave
      operation of saturablegain degenerate four-wave mixing by using a Nd:YVO(4)
      amplifier pumped by a cw Ti:sapphire laser. Such an amplifier exhibits continuous
      wave two-pass gains as high as 200, and four-wave mixing reflectivities as high
      as 30% are obtained. A theoretical analysis is developed in the steady-state
      regime to explain the experimental results.

PMID- 19862263
TI  - All-optical spatial light modulator with megahertz modulation rates.
AB  - We demonstrate a novel all-optical spatial light modulator capable of megahertz
      modulation rates. It is based on the quantum-confined Stark effect, but the
      modulating electric field is entirely photogenerated by strongly asymmetric
      photocarrier transfer in GaAs/AlAs layers. In a nonoptimized sample, cw optical
      excitation of approximately 50 W/cm(2) created a 30-kV/cm electric field,
      inducing a 9-meV exciton red shift at room temperature. Under pulsed excitation
      the photogenerated electric field can be switched on in a few tens of picoseconds
      and relaxes in a few hundred nanoseconds, permitting megahertz modulation rates.

PMID- 19862264
TI  - Theory of the effect of the laser-field-induced index grating on wavelength
      increment and gain saturation in semiconductor lasers.
AB  - A simple theory considering the laser-field-induced complex index grating is
      presented for what is to the author's knowledge the f irst time to explain and
      calculate the observed wavelength increment in semiconductor lasers as their
      output light power increases and to calculate the gain saturation in
      semiconductor lasers. The calculation results agree with the commonly accepted
      results.

PMID- 19862265
TI  - Simultaneous laser-diode emission and detection for fiber-optic sensor
      applications.
AB  - The simultaneous emission and detection of radiation with a semiconductor laser
      is investigated. Measured signal-to-noise ratios of up to 56 dB demonstrate that
      self-detecting devices are adequate for sensor applications with discrete
      measurands. We observed a strong polarization dependence, which can cause
      response fluctuations, and suggest methods to minimize these fluctuations. This
      technique could be used for lower-cost sensors without splitters and detectors.

PMID- 19862266
TI  - External-cavity semiconductor-laser array insensitive to paraxial misalignment.
AB  - We report a tilted-mirror external-cavity gain-guided laser array whose output
      power is insensitive to small misalignments of the cavity elements. This novel
      configuration delivers a near-diffraction-limited (1.5 times diffraction-limited)
      single-lobed beam in the entire current range without the need for realignment of
      the cavity. The light-current characteristic is linear and kink free, with a
      higher efficiency compared with the free-running array. A compact graded-index
      lens design that can emit a collimated beam with a circular cross section is also
      described.

PMID- 19862267
TI  - Mode locking with a compensated space-time astigmatism.
AB  - We present what is to our knowledge the first full spatial plus temporal model of
      a self-mode-locked titaniumdoped sapphire laser. The self-consistent evolution of
      the pulse toward steady state imposes strong space-time focusing in the crystal,
      where both the space and time foci are located. This combined focusing
      significantly improves the discrimination properties of the nonlinear resonator
      for shorter pulses and reduces the transient stage of pulse formation. Our
      theoretical results are in very good agreement with experiment.

PMID- 19862268
TI  - Terawatt Ti:sapphire laser with a spherical reflective-optic pulse expander.
AB  - We have developed a novel stretcher-compressor system to produce 45-fs, 75-mJ
      pulses at a 10-Hz repetition rate.

PMID- 19862269
TI  - Noise characterization of mode-locked lasers by comparing the power spectra of
      the fundamental and second-harmonic pulses.
AB  - By comparing the noise power spectra of the fundamental pulses and those of the
      second-harmonic pulses, the peak intensity fluctuation, the pulse-width
      fluctuation, the pulse timing jitter, and the cross correlation between the pulse
      width and the peak intensity f luctuations of a mode-locked pulse train can be
      separately quantified. The noise characteristics of an actively mode-locked
      Nd:YLF laser are presented to demonstrate this technique.

PMID- 19862270
TI  - Generation of 16-fs pulses at 425 nm by extracavity frequency doubling of a mode
      locked Ti:sapphire laser.
AB  - An efficient doubling scheme capable of producing 16-fs pulses centered at 425 nm
      with an average power of 40 mW is described. The system uses 15-fs pulses from a
      continuous-wave mode-locked Ti:sapphire oscillator centered at 850 nm. The pulse
      characteristics resulting from doubling with beta-barium borate crystals of
      various lengths are presented. The results compare favorably with previous
      attempts at intracavity doubling and provide a more convenient route to
      femtosecond experiments with fully synchronized second-harmonic radiation.

PMID- 19862271
TI  - Time-frame transformation for efficient simulation of chirped pulse compression
      in an optical fiber.
AB  - We propose an illustrate the use of a compressed time frame to reduce
      significantly the computational effort when simulating strong compression of
      chirped pulses in a nonlinear optical fiber. Using a lenslike transformation we
      can accurately simulate a 3-order-of-magnitude pulse compression with 128 time
      grid points only.

PMID- 19862272
TI  - Optoelectronic fuzzy associative memory with controllable attraction basin sizes.
AB  - We propose and demonstrate a new fuzzy associative memory model that provides an
      option to control the sizes of the attraction basins in neural networks. In our
      optoelectronic implementation we use spatial/polarization encoding to represent
      the fuzzy variables. Shadow casting of the encoded patterns is employed to yield
      the fuzzy-absolute difference between fuzzy variables.

PMID- 19862274
TI  - Combined binary-phase holograms for free-space optical interconnection.
AB  - We have developed a combined binary-phase hologram (CBPH) consisting of two
      binary-phase holograms. The CBPH can be used effectively for optical
      interconnection and image processing because it suppresses the unwanted images of
      a conventional binary-phase hologram. The theory and properties of the CBPH and
      experimental results are presented.

PMID- 19862273
TI  - Simultaneous reconstruction of optical absorption and scattering maps in turbid
      media from near-infrared frequency-domain data.
AB  - Simultaneously reconstructed images of both absorption and scattering coeff
      icients in optically heterogeneous media based on frequency-domain measurements
      are presented. The images are obtained from absolute measured data by use of a
      diffusion approximation to light propagation in tissue that is modeled with a
      finite-element method. Images that have different contrast levels are
      demonstrated.

PMID- 19862275
TI  - Wall relaxation of spin-polarized sodium measured by reflection spectroscopy.
AB  - Using reflection spectroscopy of optically pumped sodium vapor, we have performed
      what is to our knowledge the first direct measurement of the spatially
      inhomogeneous spin polarization near a glass surface. On the basis of a
      theoretical description of the reflection at an inhomogeneous, anisotropic
      medium, we deduce the magnitude of the small residual magnetization at the
      surface from an analysis of the optical line shape. This allows us to specify the
      depolarizing properties of the surface.

PMID- 19862276
TI  - Holographic grating formation in dye- and fullerene C(60)-doped nematic liquid
      crystal film.
AB  - Transient and persistent holographic gratings have been observed in dye- and
      fullerene C(60)-doped nematic liquid-crystal films. The nature and time evolution
      of the underlying mechanisms, such as space-charge field production, flows, and
      dielectric- and conductivity-induced torques, and the resultant director axis
      reorientation and refractive-index gratings are examined.

PMID- 19862277
TI  - Fourier-transform lidar.
AB  - We propose a new method based on the differential absorption lidar technique for
      multipollutant detection. A broadband laser is sent into the atmosphere in a
      wavelength range in which several pollutants absorb. The backscattered light is
      analyzed by a Fourier-transform spectrometer with time resolution. This mode of
      detection provides both spatial and high spectral resolution down to 0.01 cm(-1),
      allowing range-resolved measurements of several pollutants simultaneously. To
      demonstrate the feasibility of this method, we have measured water vapor
      concentration by using more than 10 individual lines in the 720-nm absorption
      band. The potential and the limitations are discussed critically.

PMID- 19862278
TI  - Spatial-frequency-multiplexed optical fiber sensor array for structure
      monitoring.
AB  - A novel optical fiber sensor system suitable for monitoring the strain/stress
      distribution of mechanical structures is reported, in which an array of
      interferometric-type sensors is integrated based on a new spatial-frequency
      multiplexing technique. It not only maintains the inherent advantage of the high
      dynamic range of interferometric sensors but also offers the additional benefits
      of simple robust system configuration, direct digital readout, and low building,
      installation, and maintenance cost. Preliminary experimental results on a
      suspension beam are reported.

PMID- 19862279
TI  - Polarization-independent all-fiber wavelength-division multiplexer based on a
      Sagnac interferometer.
AB  - An all-fiber wavelength-division multiplexer (WDM) based on the nonreciprocity of
      the birefringence to the polarization states is proposed. The transfer function
      of a Sagnac interferometer is wavelength dependent if the loop birefringence of
      the interferometer consists of both circular and linear parts. Theoretical
      analysis shows that the output characteristics of this WDM are similar to those
      of a fiber taper-based device. Both the bandwidth and the peak wavelength of the
      new WDM can be tuned by changing the loop birefringence. Experimental prototypes
      exhibit a channel isolation greater than 25 dB with peak passband insertion loss
      of less than 1 dB.

PMID- 19862280
TI  - Combined spatial- and time-division-multiplexing scheme for fiber grating sensors
      with drift-compensated phase-sensitive detection.
AB  - A combined spatial- and time-division-multiplexing topology with drift
      compensated high-resolution wavelength-shift detection is reported for fiber
      Bragg grating sensors. An eight-element grating sensor array is demonstrated
      based on this topology. A resolution of ~1.2 microepsilon over a range of ~1.5
      mepsilon with a measurement bandwidth of 30 Hz (~0.22 microepsilon/ radicalHz)
      has been achieved for quasi-static strain measurement.

PMID- 19862281
TI  - Single-step laser fabrication of refractive microlenses in semiconductor-doped
      glasses.

PMID- 19862282
TI  - Encoding of efficient diffractive microlenses.

PMID- 19862283
TI  - Characterization of high-numerical-aperture lenses by spatial autocorrelation of
      the focal field.

PMID- 19862284
TI  - Topological phase in Gaussian beam optics.

PMID- 19862285
TI  - Distortion of self-induced-transparency solitons as a result of self-phase
      modulation in ion-doped fibers.

PMID- 19862286
TI  - All-optical switching in a hybrid Mach-Zehnder interferometer as a result of
      cascaded second-order nonlinearity.

PMID- 19862287
TI  - Frequency upconversion of tunable femtosecond pulses by parametric amplification
      and sum-frequency generation in a single nonlinear crystal.

PMID- 19862288
TI  - Angular structure formation in single-pass optical parametric generators pumped
      by intersecting beams.

PMID- 19862289
TI  - Vector interactions of steady-state planar solitons in biased photorefractive
      media.

PMID- 19862290
TI  - Compositional dependence of optically encoded second-harmonic generation in pure
      binary lead-silicate and ternary barium borosilicate glasses.

PMID- 19862291
TI  - Stability of spatial solitary waves in quadratic media.

PMID- 19862292
TI  - Ultrafast nonlinear response in PLZT thin films with ultrashort pulses.

PMID- 19862293
TI  - Transient and permanent gratings in phosphosilicate optical fibers produced by
      the flash condensation technique.

PMID- 19862294
TI  - Self-tapering of elliptic Gaussian beams in an elliptic-core nonlinear fiber.

PMID- 19862295
TI  - Infrared-induced photodarkening in Tm-doped fluoride fibers.

PMID- 19862296
TI  - Improved vertical directional coupler for optimum edge coupling to an embedded
      photodetector.

PMID- 19862297
TI  - Thin-film waveguides of zirconium oxyfluoride with variable refractive index
      produced by ion-beam-assisted deposition.

PMID- 19862298
TI  - Continuous-wave 355-nm laser source based on doubly resonant sum-frequency mixing
      in an external resonator.

PMID- 19862300
TI  - Pump interference and optical bistability effects in a Tm,Ho:YAG microlaser.

PMID- 19862299
TI  - Diode-pumped, single-frequency Cr:LiSrAlF6 ring laser.

PMID- 19862301
TI  - Effect of phase-conjugate optical feedback on turn-on jitter in laser diodes.

PMID- 19862302
TI  - Optical switching in phase-shifted metal-semiconductor-metal Bragg reflectors.

PMID- 19862303
TI  - Single-cladding antiresonant reflecting optical waveguide-type diode laser.

PMID- 19862305
TI  - Femtosecond high-contrast pulses from a parametric generator pumped by the self
      compressed second harmonic of a Nd:glass laser.

PMID- 19862304
TI  - Hybrid-aligned nematic liquid-crystal modulators fabricated on VLSI circuits.

PMID- 19862306
TI  - Generation of femtosecond pulses through second-harmonic compression of the
      output of a Nd:YAG laser.

PMID- 19862307
TI  - Stimulated Raman gain scattering in thin planar dielectric waveguides.

PMID- 19862308
TI  - Log-polar dappled target.

PMID- 19862309
TI  - Influence of nonoverlapping noise on regularized linear filters for pattern
      recognition.

PMID- 19862310
TI  - Generation of amplitude-squeezed light at 431 nm from a singly resonant frequency
      doubler.

PMID- 19862311
TI  - Excitation of surface plasmons and total absorption of light at the flat boundary
      between a metal and a uniaxial crystal.

PMID- 19862312
TI  - Two-photon fluorescence excitation in continuous-wave infrared optical tweezers.

PMID- 19862313
TI  - Tilting of holograms in photorefractive Sr0.61Ba0.39Nb2O6 crystals by self
      diffraction.

PMID- 19862314
TI  - Applications of birefringent phase matching for photorefractive devices.

PMID- 19862315
TI  - Interferometric configuration based on a grating interferometer for the
      measurement of the phase between TE and TM polarizations after diffraction by
      gratings.

PMID- 19862316
TI  - Determination of the refractive index of highly scattering human tissue by
      optical coherence tomography.

PMID- 19862318
TI  - Human cell chips: adapting DNA microarray spotting technology to cell-based
      imaging assays.
AB  - Here we describe human spotted cell chips, a technology for determining cellular
      state across arrays of cells subjected to chemical or genetic perturbation. Cells
      are grown and treated under standard tissue culture conditions before being fixed
      and printed onto replicate glass slides, effectively decoupling the experimental
      conditions from the assay technique. Each slide is then probed using
      immunofluorescence or other optical reporter and assayed by automated microscopy.
      We show potential applications of the cell chip by assaying HeLa and A549 samples
      for changes in target protein abundance (of the dsRNA-activated protein kinase
      PKR), subcellular localization (nuclear translocation of NFkappaB) and activation
      state (phosphorylation of STAT1 and of the p38 and JNK stress kinases) in
      response to treatment by several chemical effectors (anisomycin, TNFalpha, and
      interferon), and we demonstrate scalability by printing a chip with approximately
      4,700 discrete samples of HeLa cells. Coupling this technology to high-throughput
      methods for culturing and treating cell lines could enable researchers to examine
      the impact of exogenous effectors on the same population of experimentally
      treated cells across multiple reporter targets potentially representing a variety
      of molecular systems, thus producing a highly multiplexed dataset with minimized
      experimental variance and at reduced reagent cost compared to alternative
      techniques. The ability to prepare and store chips also allows researchers to
      follow up on observations gleaned from initial screens with maximal
      repeatability.

PMID- 19862319
TI  - Diagnosing mechanisms of decline and planning for recovery of an endangered brown
      bear (Ursus arctos) population.
AB  - BACKGROUND: The usual paradigm for translocations is that they should not take
      place in declining populations until the causes(s) of the decline has been
      reversed. This approach sounds intuitive, but may not apply in cases where
      population decline is caused by behavioral or demographic mechanisms that could
      only be reversed by translocation itself. METHODOLOGY/PRINCIPAL FINDINGS: We
      analyzed a decade of field data for Pyrenean brown bears (Ursus arctos) from two
      small populations: the growing Central population--created from a previous
      translocation and the endemic Western population--believed to be declining
      because of excessive human-caused mortality. We found that adult survival rates
      for both populations were as high as those observed for most other protected
      brown bear populations. However, the Western population had much lower
      reproductive success than the Central population. Adult breeding sex ratio was
      male-biased in the Western population and female-biased in the Central
      population. Our results exclude high anthropogenic mortality as a cause for
      population decline in the West but support low reproductive success, which could
      result from sexually selected infanticide induced by a male-biased adult sex
      ratio or inbreeding depression. Using a stochastic demographic model to compute
      how many bears should be released to ensure viability, we show that the Western
      population could recover provided adequate numbers of new females are
      translocated. CONCLUSIONS/SIGNIFICANCE: We suggest that a translocation could
      take place, even if the decline has not yet been reversed, if the translocation
      itself removes the biological mechanisms behind the decline. In our case, the
      ultimate cause of low reproductive success remained unknown (infanticide or
      inbreeding), but our proposed translocation strategies should eliminate the
      proximate cause (low reproductive success) of the decline and ensure population
      recovery and viability.

PMID- 19862320
TI  - Fellatio by fruit bats prolongs copulation time.
AB  - Oral sex is widely used in human foreplay, but rarely documented in other
      animals. Fellatio has been recorded in bonobos Pan paniscus, but even then
      functions largely as play behaviour among juvenile males. The short-nosed fruit
      bat Cynopterus sphinx exhibits resource defence polygyny and one sexually active
      male often roosts with groups of females in tents made from leaves. Female bats
      often lick their mate's penis during dorsoventral copulation. The female lowers
      her head to lick the shaft or the base of the male's penis but does not lick the
      glans penis which has already penetrated the vagina. Males never withdrew their
      penis when it was licked by the mating partner. A positive relationship exists
      between the length of time that the female licked the male's penis during
      copulation and the duration of copulation. Furthermore, mating pairs spent
      significantly more time in copulation if the female licked her mate's penis than
      if fellatio was absent. Males also show postcopulatory genital grooming after
      intromission. At present, we do not know why genital licking occurs, and we
      present four non-mutually exclusive hypotheses that may explain the function of
      fellatio in C. sphinx.

PMID- 19862321
TI  - Why does public transport not arrive on time? The pervasiveness of equal headway
      instability.
AB  - BACKGROUND: The equal headway instability phenomenon is pervasive in public
      transport systems. This instability is characterized by an aggregation of
      vehicles that causes inefficient service. While equal headway instability is
      common, it has not been studied independently of a particular scenario. However,
      the phenomenon is apparent in many transport systems and can be modeled and
      rectified in abstraction. METHODOLOGY: We present a multi-agent simulation where
      a default method with no restrictions always leads to unstable headways. We
      discuss two methods that attempt to achieve equal headways, called minimum and
      maximum. Since one parameter of the methods depends on the passenger density,
      adaptive versions--where the relevant parameter is adjusted automatically--are
      also put forward. Our results show that the adaptive maximum method improves
      significantly over the default method. The model and simulation give insights of
      the interplay between transport design and passenger behavior. Finally, we
      provide technological and social suggestions for engineers and passengers to help
      achieve equal headways and thus reduce delays. CONCLUSIONS: The equal headway
      instability phenomenon can be avoided with the suggested technological and social
      measures.

PMID- 19862322
TI  - Bringing home the trash: do colony-based differences in foraging distribution
      lead to increased plastic ingestion in Laysan albatrosses?
AB  - When searching for prey, animals should maximize energetic gain, while minimizing
      energy expenditure by altering their movements relative to prey availability.
      However, with increasing amounts of marine debris, what once may have been
      'optimal' foraging strategies for top marine predators, are leading to sub
      optimal diets comprised in large part of plastic. Indeed, the highly vagile
      Laysan albatross (Phoebastria immutabilis) which forages throughout the North
      Pacific, are well known for their tendency to ingest plastic. Here we examine
      whether Laysan albatrosses nesting on Kure Atoll and Oahu Island, 2,150 km apart,
      experience different levels of plastic ingestion. Twenty two geolocators were
      deployed on breeding adults for up to two years. Regurgitated boluses of
      undigestable material were also collected from chicks at each site to compare the
      amount of plastic vs. natural foods. Chicks from Kure Atoll were fed almost ten
      times the amount of plastic compared to chicks from Oahu despite boluses from
      both colonies having similar amounts of natural food. Tracking data indicated
      that adults from either colony did not have core overlapping distributions during
      the early half of the breeding period and that adults from Kure had a greater
      overlap with the putative range of the Western Garbage Patch corroborating our
      observation of higher plastic loads at this colony. At-sea distributions also
      varied throughout the year suggesting that Laysan albatrosses either adjusted
      their foraging behavior according to constraints on time away from the nest or to
      variation in resources. However, in the non-breeding season, distributional
      overlap was greater indicating that the energy required to reach the foraging
      grounds was less important than the total energy available. These results
      demonstrate how a marine predator that is not dispersal limited alters its
      foraging strategy throughout the reproductive cycle to maximize energetic gain
      and how this has led to differences in plastic ingestion.

PMID- 19862323
TI  - Hydrogen peroxide stimulates activity and alters behavior in Drosophila
      melanogaster.
AB  - Circadian rhythms in animals are regulated at the level of individual cells and
      by systemic signaling to coordinate the activities of multiple tissues. The
      circadian pacemakers have several physiological outputs, including daily
      locomotor rhythms. Several redox-active compounds have been found to function in
      regulation of circadian rhythms in cells, however, how particular compounds might
      be involved in regulating specific animal behaviors remains largely unknown. Here
      the effects of hydrogen peroxide on Drosophila movement were analyzed using a
      recently developed three-dimensional real-time multiple fly tracking assay. Both
      hydrogen peroxide feeding and direct injection of hydrogen peroxide caused
      increased adult fly locomotor activity. Continuous treatment with hydrogen
      peroxide also suppressed daily locomotor rhythms. Conditional over-expression of
      the hydrogen peroxide-producing enzyme superoxide dismutase (SOD) also increased
      fly activity and altered the patterns of locomotor activity across days and
      weeks. The real-time fly tracking system allowed for detailed analysis of the
      effects of these manipulations on behavior. For example, both hydrogen peroxide
      feeding and SOD over-expression increased all fly motion parameters, however,
      hydrogen peroxide feeding caused relatively more erratic movement, whereas SOD
      over-expression produced relatively faster-moving flies. Taken together, the data
      demonstrate that hydrogen peroxide has dramatic effects on fly movement and daily
      locomotor rhythms, and implicate hydrogen peroxide in the normal control of these
      processes.

PMID- 19862324
TI  - Success in developing regions: world records evolution through a geopolitical
      prism.
AB  - A previous analysis of World Records (WR) has revealed the potential limits of
      human physiology through athletes' personal commitment. The impact of political
      factors on sports has only been studied through Olympic medals and results. Here
      we studied 2876 WR from 63 nations in four summer disciplines. We propose three
      new indicators and show the impact of historical, geographical and economical
      factors on the regional WR evolution. The south-eastward path of weighted annual
      barycenter (i.e. the average of country coordinates weighting by the WR number)
      shows the emergence of East Africa and China in WR archives. Home WR ratio
      decreased from 79.9% before the second World War to 23.3% in 2008, underlining
      sports globalization. Annual Cumulative Proportions (ACP, i.e. the cumulative sum
      of the WR annual rate) highlight the regional rates of progression. For all
      regions, the mean slope of ACP during the Olympic era is 0.0101, with a maximum
      between 1950 and 1989 (0.0156). For European countries, this indicator reflects
      major historical events (slowdown for western countries after 1945, slowdown for
      eastern countries after 1990). Mean North-American ACP slope is 0.0029 over the
      century with an acceleration between 1950 and 1989 at 0.0046. Russia takes off in
      1935 and slows down in 1988 (0.0038). For Eastern Europe, maximal progression is
      seen between 1970 and 1989 (0.0045). China starts in 1979 with a maximum between
      1990 and 2008 (0.0021), while other regions have largely declined (mean ACP slope
      for all other countries = 0.0011). A similar trend is observed for the evolution
      of the 10 best performers. The national analysis of WR reveals a precise and
      quantifiable link between the sport performances of a country, its historical or
      geopolitical context, and its steps of development.

PMID- 19862325
TI  - PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are
      associated with type 2 diabetes in a Chinese population.
AB  - BACKGROUND: Recent advance in genetic studies added the confirmed susceptible
      loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the
      independent and joint effect of variants from these loci on type 2 diabetes and
      clinical phenotypes related to glucose metabolism. METHODS/PRINCIPAL FINDINGS:
      Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were
      successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects
      with normal glucose regulation. We analyzed the allele and genotype distribution
      between the cases and controls of these SNPs as well as the joint effects of the
      susceptible loci on type 2 diabetes risk. The associations between SNPs and type
      2 diabetes were examined by logistic regression. The associations between SNPs
      and quantitative traits were examined by linear regression. The discriminative
      accuracy of the prediction models was assessed by area under the receiver
      operating characteristic curves. We confirmed the effects of SNPs from PPARG,
      KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for
      type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from
      0.0335 to 1.37E-12). But no significant association was detected between SNPs
      from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2
      diabetes. Analyses on the quantitative traits in the control subjects showed that
      THADA SNP rs7578597 was association with 2-h insulin during oral glucose
      tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of
      SNPs from eleven loci showed the individual carrying more risk alleles had a
      significantly higher risk for type 2 diabetes. And the type 2 diabetes patients
      with more risk allele tended to have earlier diagnostic ages (P = 0.0006).
      CONCLUSIONS/SIGNIFICANCE: The current study confirmed the association between
      PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and
      type 2 diabetes. These type 2 diabetes risk loci contributed to the disease
      additively.

PMID- 19862326
TI  - Retinoic acid mediates long-paced oscillations in retinoid receptor activity:
      evidence for a potential role for RIP140.
AB  - BACKGROUND: Mechanisms that underlie oscillatory transcriptional activity of
      nuclear receptors (NRs) are incompletely understood. Evidence exists for rapid,
      cyclic recruitment of coregulatory complexes upon activation of nuclear
      receptors. RIP140 is a NR coregulator that represses the transactivation of
      agonist-bound nuclear receptors. Previously, we showed that RIP140 is inducible
      by all-trans retinoic acid (RA) and mediates limiting, negative-feedback
      regulation of retinoid signaling. METHODOLOGY AND FINDINGS: Here we report that
      in the continued presence of RA, long-paced oscillations of retinoic acid
      receptor (RAR) activity occur with a period ranging from 24 to 35 hours.
      Endogenous expression of RIP140 and other RA-target genes also oscillate in the
      presence of RA. Cyclic retinoid receptor transactivation is ablated by
      constitutive overexpression of RIP140. Further, depletion of RIP140 disrupts
      cyclic expression of the RA target gene HOXA5. Evidence is provided that RIP140
      may limit RAR signaling in a selective, non-redundant manner in contrast to the
      classic NR coregulators NCoR1 and SRC1 that are not RA-inducible, do not cycle,
      and may be partially redundant in limiting RAR activity. Finally, evidence is
      provided that RIP140 can repress and be induced by other nuclear receptors in a
      manner that suggests potential participation in other NR oscillations.
      CONCLUSIONS AND SIGNIFICANCE: We provide evidence for novel, long-paced
      oscillatory retinoid receptor activity and hypothesize that this may be paced in
      part, by RIP140. Oscillatory NR activity may be involved in mediating hormone
      actions of physiological and pathological importance.

PMID- 19862327
TI  - Rab11 helps maintain apical crumbs and adherens junctions in the Drosophila
      embryonic ectoderm.
AB  - BACKGROUND: Tissue morphogenesis and organogenesis require that cells retain
      stable cell-cell adhesion while changing shape and moving. One mechanism to
      accommodate this plasticity in cell adhesion involves regulated trafficking of
      junctional proteins. METHODOLOGY/PRINCIPAL FINDINGS: Here we explored trafficking
      of junctional proteins in two well-characterized model epithelia, the Drosophila
      embryonic ectoderm and amnioserosa. We find that DE-cadherin, the transmembrane
      protein of adherens junctions, is actively trafficked through putative vesicles,
      and appears to travel through both Rab5-positive and Rab11-positive structures.
      We manipulated the functions of Rab11 and Rab5 to examine the effects on
      junctional stability and morphogenesis. Reducing Rab11 function, either using a
      dominant negative construct or loss of function alleles, disrupts integrity of
      the ectoderm and leads to loss of adherens junctions. Strikingly, the apical
      junctional regulator Crumbs is lost before AJs are destabilized, while the
      basolateral protein Dlg remains cortical. Altering Rab5 function had less
      dramatic effects, not disrupting adherens junction integrity but affecting dorsal
      closure. CONCLUSIONS/SIGNIFICANCE: We contrast our results with what others saw
      when disrupting other trafficking regulators, and when disrupting Rab function in
      other tissues; together these data suggest distinct mechanisms regulate
      junctional stability and plasticity in different tissues.

PMID- 19862328
TI  - Could work be a source of behavioural disorders? A study in horses.
AB  - Stress at work, as shown by a number of human studies, may lead to a variety of
      negative and durable effects, such as impaired psychological functioning
      (anxiety, depression...). Horses share with humans this characteristic of working
      on a daily basis and are submitted then to work stressors related to physical
      constraints and/or more "psychological" conflicts, such as potential
      controversial orders from the riders or the requirement to suppress emotions. On
      another hand, horses may perform abnormal repetitive behaviour ("stereotypies")
      in response to adverse life conditions. In the present study, we investigated
      whether the type of work the horses are used for may have an impact on their
      tendency to show stereotypic behaviour (and its type) outside work. Observations
      in their box of 76 horses all living in the same conditions, belonging to one
      breed and one sex, revealed that the prevalence and types of stereotypies
      performed strongly depended upon the type of work they were used for. The
      stereotypies observed involved mostly mouth movements and head tossing/nodding.
      Work constraints probably added to unfavourable living conditions, favouring the
      emergence of chronic abnormal behaviours. This is especially remarkable as the 23
      hours spent in the box were influenced by the one hour work performed every day.
      To our knowledge, this is the first evidence of potential effects of work
      stressors on the emergence of abnormal behaviours in an animal species. It raises
      an important line of thought on the chronic impact of the work situation on the
      daily life of individuals.

PMID- 19862329
TI  - Early activation of FGF and nodal pathways mediates cardiac specification
      independently of Wnt/beta-catenin signaling.
AB  - BACKGROUND: Cardiac induction, the first step in heart development in vertebrate
      embryos, is thought to be initiated by anterior endoderm during gastrulation, but
      what the signals are and how they act is unknown. Several signaling pathways,
      including FGF, Nodal, BMP and Wnt have been implicated in cardiac specification,
      in both gain- and loss-of-function experiments. However, as these pathways
      regulate germ layer formation and patterning, their specific roles in cardiac
      induction have been difficult to define. METHODOLOGY/PRINCIPAL FINDINGS: To
      investigate the mechanisms of cardiac induction directly we devised an assay
      based on conjugates of anterior endoderm from early gastrula stage Xenopus
      embryos as the inducing tissue and pluripotent ectodermal explants as the
      responding tissue. We show that the anterior endoderm produces a specific signal,
      as skeletal muscle is not induced. Cardiac inducing signal needs up to two hours
      of interaction with the responding tissue to produce an effect. While we found
      that the BMP pathway was not necessary, our results demonstrate that the FGF and
      Nodal pathways are essential for cardiogenesis. They were required only during
      the first hour of cardiogenesis, while sustained activation of ERK was required
      for at least four hours. Our results also show that transient early activation of
      the Wnt/beta-catenin pathway has no effect on cardiogenesis, while later
      activation of the pathway antagonizes cardiac differentiation.
      CONCLUSIONS/SIGNIFICANCE: We have described an assay for investigating the
      mechanisms of cardiac induction by anterior endoderm. The assay was used to
      provide evidence for a direct, early and transient requirement of FGF and Nodal
      pathways. In addition, we demonstrate that Wnt/beta-catenin pathway plays no
      direct role in vertebrate cardiac specification, but needs to be suppressed just
      prior to differentiation.

PMID- 19862330
TI  - The cellular architecture of the larval zebrafish tectum, as revealed by gal4
      enhancer trap lines.
AB  - We have carried out a Gal4 enhancer trap screen in zebrafish, and have generated
      184 stable transgenic lines with interesting expression patterns throughout the
      nervous system. Of these, three display clear expression in the tectum, each with
      a distinguishable and stereotyped distribution of Gal4 expressing cells. Detailed
      morphological analysis of single cells, using a genetic "Golgi-like" labelling
      method, revealed four common cell types (superficial, periventricular, shallow
      periventricular, and radial glial), along with a range of other less common
      neurons. The shallow periventricular (PV) and a subset of the PV neurons are
      tectal efferent neurons that target various parts of the reticular formation. We
      find that it is specifically PV neurons with dendrites in the deep tectal
      neuropil that target the reticular formation. This indicates that these neurons
      receive the tectum's highly processed visual information (which is fed from the
      superficial retinorecipient layers), and relay it to premotor regions. Our
      results show that the larval tectum, both broadly and at the single cell level,
      strongly resembles a miniature version of its adult counterpart, and that it has
      all of the necessary anatomical characteristics to inform motor responses based
      on sensory input. We also demonstrate that mosaic expression of GFP in Gal4
      enhancer trap lines can be used to describe the types and abundance of cells in
      an expression pattern, including the architectures of individual neurons. Such
      detailed anatomical descriptions will be an important part of future efforts to
      describe the functions of discrete tectal circuits in the generation of behavior.

PMID- 19862331
TI  - A second-site noncomplementation screen for modifiers of Rho1 signaling during
      imaginal disc morphogenesis in Drosophila.
AB  - BACKGROUND: Rho1 is a small GTPase of the Ras superfamily that serves as the
      central component in a highly conserved signaling pathway that regulates tissue
      morphogenesis during development in all animals. Since there is tremendous
      diversity in the upstream signals that can activate Rho1 as well as the effector
      molecules that carry out its functions, it is important to define relevant Rho1
      interacting genes for each morphogenetic event regulated by this signaling
      pathway. Previous work from our lab and others has shown that Rho signaling is
      necessary for the morphogenesis of leg imaginal discs during metamorphosis in
      Drosophila, although a comprehensive identification of Rho1-interacting genes has
      not been attempted for this process. METHODOLOGY/PRINCIPAL FINDINGS: We
      characterized an amorphic allele of Rho1 that displays a poorly penetrant
      dominant malformed leg phenotype and is capable of being strongly enhanced by
      Rho1-interacting heterozygous mutations. We then used this allele in a second
      site noncomplementation screen with the Exelixis collection of molecularly
      defined deficiencies to identify Rho1-interacting genes necessary for leg
      morphogenesis. In a primary screen of 461 deficiencies collectively uncovering
      approximately 50% of the Drosophila genome, we identified twelve intervals
      harboring Rho1-interacting genes. Through secondary screening we identified six
      Rho1-interacting genes including three that were previously identified (RhoGEF2,
      broad, and stubbloid), thereby validating the screen. In addition, we identified
      Cdc42, Rheb and Sc2 as novel Rho1-interacting genes involved in adult leg
      development. CONCLUSIONS/SIGNIFICANCE: This screen identified well-known and
      novel Rho1-interacting genes necessary for leg morphogenesis, thereby increasing
      our knowledge of this important signaling pathway. We additionally found that
      Rheb may have a unique function in leg morphogenesis that is independent of its
      regulation of Tor.

PMID- 19862332
TI  - Heme mediates cytotoxicity from artemisinin and serves as a general anti
      proliferation target.
AB  - Heme (Fe2+ protoporphyrin IX) is an essential molecule that has been implicated
      the potent antimalarial action of artemisinin and its derivatives, although the
      source and nature of the heme remain controversial. Artemisinins also exhibit
      selective cytotoxicity against cancer cells in vitro and in vivo. We demonstrate
      that intracellular heme is the physiologically relevant mediator of the cytotoxic
      effects of artemisinins. Increasing intracellular heme synthesis through the
      addition of aminolevulinic acid, protoporphyrin IX, or transferrin-bound iron
      increased the cytotoxicity of dihydroartemisinin, while decreasing heme synthesis
      through the addition of succinyl acetone decreased its cytotoxic activity. A
      simple and robust high throughput assay was developed to screen chemical
      compounds that were capable of interacting with heme. A natural products library
      was screened which identified the compound coralyne, in addition to artemisinin,
      as a heme interacting compound with heme synthesis dependent cytotoxic activity.
      These results indicate that cellular heme may serve a general target for the
      development of both anti-parasitic and anti-cancer therapeutics.

PMID- 19862333
TI  - Sequence variations of GRM6 in patients with high myopia.
AB  - PURPOSE: Mutations in the glutamate receptor metabotropic 6 gene (GRM6) have been
      identified in patients with congenital stationary night blindness (CSNB1B). High
      myopia is usually observed in CSNB1B patients. This study tested if any mutations
      in GRM6 were solely responsible for high myopia. METHODS: DNA was prepared from
      the venous leukocytes of 96 Chinese patients with high myopia (refraction of
      spherical equivalent of at least -6.00 diopters [D]) and 96 controls (refraction
      of spherical equivalent between -0.50 D and +2.00 D with normal visual acuity).
      The coding regions and adjacent intronic sequence of GRM6 were amplified by a
      polymerase chain reaction (PCR) and then analyzed by cycle sequencing. Detected
      variations were evaluated in normal controls by heteroduplex-single-strand
      conformation (SSCP) polymorphism analysis or restriction fragment polymorphism
      (RFLP). RESULTS: Four novel variations predicted to have potential functional
      changes were identified: c.67-82delCAGGCGGGCCTGGCGCinsT (p.Gln23_Arg28delinsCys),
      c.858-5a>g (r.spl?), c.1172G>A (p.Arg391Gln), and c.1537G>A (p.Val513Met). Except
      for c.1172G>A, the other three were not detected in the 96 controls. In addition,
      five rare variations-(c.72G>A, c.504+10g>t, c.726-50g>c, c.1359C>T, and
      c.1383C>T)-and one common variation (c.2437-6g>a) without predicted functional
      consequences and nine known single nucleotide polymorphisms (SNPs) were also
      detected. CONCLUSION: Three novel variations with potential functional
      consequences were identified in the GRM6 of patients with high myopia, suggesting
      a potential role in the development of myopia in rare cases.

PMID- 19862334
TI  - TGF-beta-induced interleukin-6 participates in transdifferentiation of human
      Tenon's fibroblasts to myofibroblasts.
AB  - PURPOSE: To gain a better understanding of the roles of interleukins (ILs) in
      subconjunctival fibrosis, we investigated their expression in transforming growth
      factor-beta1 (TGF-beta1)-stimulated Tenon's fibroblasts and examined their
      association with the transdifferentiation of fibroblasts to myofibroblasts.
      METHODS: After primary culture, fibroblasts derived from human Tenon's capsule
      were exposed to TGF-beta1. The expression of alpha-smooth muscle actin (alpha
      SMA) protein was assessed by western immunoblots and immunofluorescence. The mRNA
      levels of various ILs were also evaluated by multiplex reverse transcription (RT)
      PCR. Using the small interfering RNAs (siRNAs) specific for IL-6 and IL-11 and
      the promoter deletion assay, the contributions of IL-6 and IL-11 to TGF-beta1
      induced induction of alpha-SMA were determined. RESULTS: In human Tenon's
      fibroblasts, TGF-beta1 stimulated the expression of alpha-SMA protein determined
      by western blot analysis and also increased the mRNA levels of IL-6 and IL-11
      determined by multiplex RT-PCR. On the western immunoblots and
      immunofluorescence, the increased expression of alpha-SMA was attenuated only by
      the siRNAs specific for IL-6 but not by the siRNAs specific for IL-11. When the
      activator protein-1 binding sites of the IL-6 promoter region were deleted, the
      stimulation effects of TGF-beta1 decreased. CONCLUSIONS: Our data show that
      autocrine IL-6 may participate in the TGF-beta1-induced transdifferentiation of
      human Tenon's fibroblasts to myofibroblasts, which is known to be an essential
      step for subconjunctival fibrosis.

PMID- 19862335
TI  - PAX6 aniridia and interhemispheric brain anomalies.
AB  - PURPOSE: To report the clinical and genetic study of patients with autosomal
      dominant aniridia. METHODS: We studied ten patients with aniridia from three
      families of Egyptian origin. All patients underwent full ophthalmologic, general
      and neurological examination, and blood drawing. Cerebral magnetic resonance
      imaging was performed in the index case of each family. Genomic DNA was prepared
      from venous leukocytes, and direct sequencing of all the exons and intron-exon
      junctions of the Paired Box gene 6 (PAX6) was performed after PCR amplification.
      Phenotype description, including ophthalmic and cerebral anomalies, mutation
      detection in PAX6 and phenotype-genotype correlation was acquired. RESULTS:
      Common features observed in the three families included absence of iris tissue,
      corneal pannus with different degrees of severity, and foveal hypoplasia with
      severely reduced visual acuity. In Families 2 and 3, additional findings, such as
      lens dislocation, lens opacities or polar cataract, and glaucoma, were observed.
      We identified two novel (c.170-174delTGGGC [p.L57fs17] and c.475delC
      [p.R159fs47]) and one known (c.718C>T [p.R240X]) PAX6 mutations in the affected
      members of the three families. Systemic and neurological examination was normal
      in all ten affected patients. Cerebral magnetic resonance imaging showed absence
      of the pineal gland in all three index patients. Severe hypoplasia of the brain
      anterior commissure was associated with the p.L57fs17 mutation, absence of the
      posterior commissure with p.R159fs47, and optic chiasma atrophy and almost
      complete agenesis of the corpus callosum with p.R240X. CONCLUSIONS: We identified
      two novel PAX6 mutations in families with severe aniridia. In addition to common
      phenotype of aniridia and despite normal neurological examination, absence of the
      pineal gland and interhemispheric brain anomalies were observed in all three
      index patients. The heterogeneity of PAX6 mutations and brain anomalies are
      highlighted. This report emphasizes the association between aniridia and brain
      anomalies with or without functional impact, such as neurodevelopment delay or
      auditory dysfunction.

PMID- 19862336
TI  - Retinal ischemia-induced apoptosis is associated with alteration in Bax and Bcl
      x(L) expression rather than modifications in Bak and Bcl-2.
AB  - PURPOSE: Apoptosis is known to play a key role in cell death after retinal
      ischemia. However, little is known about the kinetics of the signaling pathways
      involved and their contribution to this process. The aim of this study was to
      determine whether changes in the expression of molecules in the mitochondrial
      apoptotic pathway might explain the progression of retinal damage following
      ischemia/reperfusion. METHODS: Retinal ischemia was induced by elevating
      intraocular pressure in the vitreous cavity to 150 mmHg for a period of 60 min.
      At time 0, 3 h (early phase), and 24 h (late phase) after reperfusion, the
      retinas were harvested and modifications in the expression of Bax, Bak, Bcl-2,
      and Bcl-x(L) as well as caspase-3 and -7, were examined by qPCR and, in some
      cases, by western blot. RESULTS: qPCR analysis performed at the early phase after
      ischemia revealed a time dependent decrease in Bax, Bak, and Bcl-x(L) and no
      alteration in Bcl-2 mRNA expression in response to retinal ischemia. At the
      protein level, proapoptotic Bax and Bak were not modulated while Bcl-2 and Bcl
      x(L) were significantly upregulated. At this stage, the Bax per Bcl-2 and Bax:Bcl
      x(L) ratios were not modified. At the late phase of recovery, Bax and Bcl-x(L)
      mRNAs were downregulated while Bak was increased. Increased Bax:Bcl-2 and Bax:Bcl
      x(L) ratios at both the mRNA and protein levels were observed 24 h after the
      ischemic insult. Analysis of caspases associated with mitochondria-mediated
      apoptosis revealed a specific increase in the expression of caspase-3 in the
      ischemic retinas 24 h after reperfusion, and a decrease in the expression of
      caspase-7. CONCLUSIONS: This study revealed that Bcl-2-related family members
      were differently regulated in the early and late phases after an ischemic insult.
      We showed that the Bax:Bcl-2 and Bax:Bcl-x(L) balances were not affected in the
      initial phases, but the Bax:Bcl-x(L) ratio shifted toward apoptosis during the
      late phase of recovery. This shift was reinforced by caspase-3 upregulation.

PMID- 19862337
TI  - Reconstruction of a human hemicornea through natural scaffolds compatible with
      the growth of corneal epithelial stem cells and stromal keratocytes.
AB  - PURPOSE: To reconstruct a human hemicornea in vitro by means of limbal stem cells
      cultured onto human keratoplasty lenticules (HKLs) and to obtain a natural
      corneal graft for clinical applications. METHODS: Limbal stem cells were seeded
      onto HKLs with or without the presence of feeder layers of lethally irradiated
      3T3-J2 cells and compared with the current "gold standard" scaffold, i.e., the
      fibrin glue. The effects of the scaffold on the preservation of stemness and/or
      induction of differentiation pathways were investigated through analysis of a
      variety of markers, including p63 and DeltaNp63alpha for stemness, 14-3-3sigma
      for early differentiation, keratins 3, 14, 12, and 19 to determine cell
      phenotype, and alpha6, beta1, and beta4 integrins to evaluate interactions with
      the stroma. Integrity of the stroma was assessed through analysis of keratan
      sulfate, CD-34 and aldehyde dehydrogenase 3A1 (ALDH3A1) (for keratocytes), visual
      system homeobox 1 (VSX1), and alpha-smooth muscle actin (alpha-SMA) (for
      fibroblasts and myofibroblasts). The structural properties of the reconstructed
      "hemicornea" were investigated through scanning electron microscopy. To evaluate
      the preservation of the stemness potential, cells were trypsinized from each
      scaffold and clonogenic/proliferative characteristics analyzed. RESULTS: Limbal
      stem cells expanded onto HKLs gave rise to a stratified squamous keratinized
      epithelium morphologically similar to that of normal corneas. The resulting
      corneal epithelium was characterized by basal expression of p63 and
      DeltaNp63alpha, while expression of 14-3-3sigma, keratin 3, and keratin 12 was
      found in the upper cell layers. The basal cuboidal epithelial cells were anchored
      to the basement membrane and expressed keratin 14 and alpha6, beta1, and beta4
      integrins. In the stroma of HKLs, keratocytes maintained the biosynthetic and
      phenotypic appearances typical of resting/quiescent cells and expressed keratan
      sulfate, CD-34, and ALDH3A1. Fibroblastic transformation was observed with the
      appearance of VSX1 and alpha-SMA. Scanning electron microscopy analysis showed
      that HKLs maintained their native conformation with collagen fibrils
      interconnected to the network and parallel to the corneal surface. HKLs did not
      alter the clonogenic/proliferative capacity of limbal stem cells. No differences
      were seen when HKL was compared to fibrin glue, one of the scaffolds currently
      used for limbal stem cell transplantation. CONCLUSIONS: Our findings demonstrate
      that HKL could be a suitable scaffold for corneal epithelial stem cells as they
      were shown to proliferate, express differentiation markers, and bind to the
      underlying stroma with no alterations in clonogenic potential. HKLs have some
      advantages over currently used scaffolds, such as the possibility to allow cell
      growth with no feeder layers, to be freeze dried, and to preserve the integrity
      and viability of stromal keratocytes. The development of a tissue-engineered
      "hemicornea" might offer new therapeutic perspectives to patients affected by
      total limbal stem cell deficiency with stromal scarring.

PMID- 19862338
TI  - Sequential changes in the gene expression profile of murine retinal progenitor
      cells during the induction of differentiation.
AB  - PURPOSE: Following transplantation, cultured retinal progenitor cells (RPCs)
      integrate into the diseased host retina and exhibit morphologies and markers
      indicative of local cellular phenotypes. In vitro analysis of cultured RPCs
      allows detailed examination of marker gene expression during the initial phase of
      differentiation and can provide insight into the variables influencing this
      process. METHODS: Using cultured murine RPCs, this study compares the effects of
      fetal bovine serum (FBS) with those of ciliary neurotrophic factor (CNTF),
      individually or in combination with epidermal growth factor (EGF).
      Differentiation was assessed by way of the relative expression of 17 genes using
      quantitative PCR (qPCR) at five time points over a seven-day period. RESULTS:
      Both CNTF and FBS rapidly altered the gene expression of RPCs, with very marked
      upregulation of glial fibrillary acidic protein (GFAP; FBS>CNTF) and marked down
      regulation of the proliferation marker K(i)-67, consistent with the induction of
      differentiation. The evidence supports a preponderantly pro-glial influence for
      both the FBS and CNTF, however, neuronal markers were also upregulated to a
      lesser extent. Immunocytochemistry confirmed subpopulations labeling with
      neuronal markers, including rhodopsin. In the presence of sustained EGF
      stimulation, the differentiating influences of both FBS and CNTF remained
      perceptible as transient peaks of relative gene expression, but were markedly
      diminished overall. CONCLUSIONS: This study shows that it is possible to compare
      the relative efficacy of in vitro differentiation protocols using murine RPCs and
      qPCR. The differentiating influences of both serum and CNTF were confirmed, but
      shown to be powerfully moderated by EGF. This suggests that EGF withdrawal is the
      dominant feature of these differentiation protocols and that exposure to either
      serum or CNTF is insufficient to irreversibly commit a cultured RPC population to
      terminal differentiation unless accompanied by concomitant cessation of mitogenic
      stimulation.

PMID- 19862339
TI  - ETX1 is over-expressed in the glaucomatous trabecular meshwork.
AB  - PURPOSE: To determine whether exon-trapped X chromosome clone 1 (ETX1) is
      overexpressed in the trabecular meshwork (TM) of glaucomatous human eyes compared
      to controls. METHODS: Immunohistochemical, western blot, and enzyme-linked
      immunosorbent assay analysis were used with human tissues and TM protein
      extracts. Reverse transcription-PCR was performed on isolated mRNA-derived cDNA
      preparations. RESULTS: Elevated expression levels of ETX1 were detected in
      glaucomatous compared to control TM tissue. This corroborates previous detection
      of ETX1 in glaucomatous TM by proteomic analysis. ETX1 mRNA is present in TM
      tissue, suggesting ETX1 protein is locally produced within TM cells. CONCLUSIONS:
      This is the first report demonstrating overexpression of ETX1 in glaucomatous TM.
      ETX1 expression may regulate TM protein interactions involved in cell adhesion,
      and its aberrant overexpression may be part of the pathophysiological pathway in
      the development of glaucoma.

PMID- 19862340
TI  - Study of the expression of CD30 in pterygia compared to healthy conjunctivas.
AB  - PURPOSE: The pterygium is characterized by a fibrovascular neoformation from the
      bulbar conjunctiva into the cornea. The recent discovery that abnormal markers
      associated with tumor diseases are identified in the pterygium strengthens the
      theory that the pterygium is a tumor-like disease rather than a degenerative
      disease. The CD30 molecule has been identified in neoplastic and normal
      epithelial proliferating cells. The aim of this study was to determine the
      expression of the CD30 molecule in the pterygium. METHODS: Immunohistochemical
      staining using an antibody to CD30 and to the Ki-67 nuclear antigen was performed
      on 25 pterygial specimens and 10 healthy conjunctivas. RESULTS: Strong
      immunostaining against CD30 was observed in all pterygium specimens, in contrast
      to the healthy conjunctivas that showed weak immono-positivity in only three
      cases. The staining was diffused, predominantly to the basal epithelium. The Ki
      67 antigen was observed in the nucleus of the basal epithelium of the pterygial
      specimens, and no staining was observed in the healthy conjunctiva. When serial
      sections were stained with CD30 and Ki-67, the cells that expressed CD30 also
      expressed Ki-67. CONCLUSIONS: The present study identified for the first time the
      existence of CD30 molecules in the basal epithelium of a pterygium. The fact that
      the positivity to Ki-67 in the basal epithelium of the pterygium correlated with
      the CD30 reactivity suggested that this protein could be associated with the
      uncontrolled cell proliferation of the epithelium in this pathology. The CD30
      molecule could therefore be a suitable target to be inhibited using chimerical
      antibodies in pterygium diseases.

PMID- 19862342
TI  - Exploration of fluorescent protein voltage probes based on circularly permuted
      fluorescent proteins.
AB  - Genetically encoded fluorescent protein (FP) voltage sensors are promising tools
      for optical monitoring of the electrical activity of cells. Over the last decade,
      several designs of fusion proteins have been explored and some of them have
      proven to be sensitive enough to record membrane voltage transients from single
      mammalian cells. Most prominent are the families of voltage sensitive fluorescent
      proteins (VSFPs) that utilize the voltage sensor domain (VSD) of Ciona
      intestinalis voltage sensor-containing phosphatase (Ci-VSP). The voltage
      sensitivity of the fluorescence readout of these previously reported membrane
      potential indicators is achieved either via a change in the efficiency of
      fluorescence resonance energy transfer between two FP spectral variants or via
      modulation in the fluorescence intensity of a single FP. Here, we report our
      exploration on a third VSFP design principle based on circularly permuted
      fluorescent protein (cpFP) variants. Using circularly permuted EGFP derived from
      GCaMP2 and two newly generated circularly permuted variants of the far-red
      emitting protein named mKate, we generated and characterized a series of voltage
      sensitive probes wherein the cpFPs were fused to the VSD of Ci-VSP. The most
      promising variants were based on circularly permuted mKate with new N- and C
      termini given by residues 180 and 182. Even so their voltage sensitivity was
      relatively modest, they constitute a proof of principle for this novel protein
      design.

PMID- 19862343
TI  - Performance- and stimulus-dependent oscillations in monkey prefrontal cortex
      during short-term memory.
AB  - Short-term memory requires the coordination of sub-processes like encoding,
      retention, retrieval and comparison of stored material to subsequent input.
      Neuronal oscillations have an inherent time structure, can effectively coordinate
      synaptic integration of large neuron populations and could therefore organize and
      integrate distributed sub-processes in time and space. We observed field
      potential oscillations (14-95 Hz) in ventral prefrontal cortex of monkeys
      performing a visual memory task. Stimulus-selective and performance-dependent
      oscillations occurred simultaneously at 65-95 Hz and 14-50 Hz, the latter being
      phase-locked throughout memory maintenance. We propose that prefrontal
      oscillatory activity may be instrumental for the dynamical integration of local
      and global neuronal processes underlying short-term memory.

PMID- 19862344
TI  - Doublecortin-expressing cells persist in the associative cerebral cortex and
      amygdala in aged nonhuman primates.
AB  - A novel population of cells that express typical immature neuronal markers
      including doublecortin (DCX+) has been recently identified throughout the adult
      cerebral cortex of relatively large mammals (guinea pig, rabbit, cat, monkey and
      human). These cells are more common in the associative relative to primary
      cortical areas and appear to develop into interneurons including type II
      nitrinergic neurons. Here we further describe these cells in the cerebral cortex
      and amygdala, in comparison with DCX+ cells in the hippocampal dentate gyrus, in
      three age groups of rhesus monkeys: young adult (12.3 +/- 0.2 years, n = 3), mid
      age (21.2 +/- 1.9 years, n = 3) and aged (31.3 +/- 1.8 years, n = 4). DCX+ cells
      with a heterogeneous morphology persisted in layers II/III primarily over the
      associative cortex and amygdala in all groups (including in two old animals with
      cerebral amyloid pathology), showing a parallel decline in cell density with age
      across regions. In contrast to the cortex and amygdala, DCX+ cells in the
      subgranular zone diminished in the mid-age and aged groups. DCX+ cortical cells
      might arrange as long tangential migratory chains in the mid-age and aged
      animals, with apparently distorted cell clusters seen in the aged group. Cortical
      DCX+ cells colocalized commonly with polysialylated neural cell adhesion molecule
      and partially with neuron-specific nuclear protein and gamma-aminobutyric acid,
      suggesting a potential differentiation of these cells into interneuron phenotype.
      These data suggest a life-long role for immature interneuron-like cells in the
      associative cerebral cortex and amygdala in nonhuman primates.

PMID- 19862345
TI  - Experience-driven formation of parts-based representations in a model of layered
      visual memory.
AB  - Growing neuropsychological and neurophysiological evidence suggests that the
      visual cortex uses parts-based representations to encode, store and retrieve
      relevant objects. In such a scheme, objects are represented as a set of spatially
      distributed local features, or parts, arranged in stereotypical fashion. To
      encode the local appearance and to represent the relations between the
      constituent parts, there has to be an appropriate memory structure formed by
      previous experience with visual objects. Here, we propose a model how a
      hierarchical memory structure supporting efficient storage and rapid recall of
      parts-based representations can be established by an experience-driven process of
      self-organization. The process is based on the collaboration of slow
      bidirectional synaptic plasticity and homeostatic unit activity regulation, both
      running at the top of fast activity dynamics with winner-take-all character
      modulated by an oscillatory rhythm. These neural mechanisms lay down the basis
      for cooperation and competition between the distributed units and their synaptic
      connections. Choosing human face recognition as a test task, we show that, under
      the condition of open-ended, unsupervised incremental learning, the system is
      able to form memory traces for individual faces in a parts-based fashion. On a
      lower memory layer the synaptic structure is developed to represent local facial
      features and their interrelations, while the identities of different persons are
      captured explicitly on a higher layer. An additional property of the resulting
      representations is the sparseness of both the activity during the recall and the
      synaptic patterns comprising the memory traces.

PMID- 19862346
TI  - Subplate cells: amplifiers of neuronal activity in the developing cerebral
      cortex.
AB  - Due to their unique structural and functional properties, subplate cells are
      ideally suited to function as important amplifying units within the developing
      neocortical circuit. Subplate neurons have extensive dendritic and axonal
      ramifications and relatively mature functional properties, i.e. their action
      potential firing can exceed frequencies of 40 Hz. At earliest stages of
      corticogenesis subplate cells receive functional synaptic inputs from the
      thalamus and from other cortical and non-cortical sources. Glutamatergic and
      depolarizing GABAergic inputs arise from cortical neurons and neuromodulatory
      inputs arise from the basal forebrain and other sources. Activation of
      postsynaptic metabotropic receptors, i.e. muscarinic receptors, elicits in
      subplate neurons oscillatory burst discharges which are transmitted via
      electrical and chemical synapses to neighbouring subplate cells and to immature
      neurons in the cortical plate. The tonic non-synaptic release of GABA from
      GABAergic subplate cells facilitates the generation of burst discharges. These
      cellular bursts are amplified by prominent gap junction coupling in the subplate
      and cortical plate, thereby eliciting 10-20 Hz oscillations in a local columnar
      network. Thus, we propose that neuronal networks are organized at earliest stages
      in a gap junction coupled columnar syncytium. We postulate that the subplate does
      not only serve as a transient relay station for afferent inputs, but rather as an
      active element amplifying the afferent and intracortical activity.

PMID- 19862347
TI  - Attention to Speech-Accompanying Gestures: Eye Movements and Information Uptake.
AB  - There is growing evidence that addressees in interaction integrate the semantic
      information conveyed by speakers' gestures. Little is known, however, about
      whether and how addressees' attention to gestures and the integration of gestural
      information can be modulated. This study examines the influence of a social
      factor (speakers' gaze to their own gestures), and two physical factors (the
      gesture's location in gesture space and gestural holds) on addressees' overt
      visual attention to gestures (direct fixations of gestures) and their uptake of
      gestural information. It also examines the relationship between gaze and uptake.
      The results indicate that addressees' overt visual attention to gestures is
      affected both by speakers' gaze and holds but for different reasons, whereas
      location in space plays no role. Addressees' uptake of gesture information is
      only influenced by speakers' gaze. There is little evidence of a direct
      relationship between addressees' direct fixations of gestures and their uptake.

PMID- 19862348
TI  - Neonatal injury alters adult pain sensitivity by increasing opioid tone in the
      periaqueductal gray.
AB  - Studies in both rodents and humans have shown that acute inflammatory pain
      experienced during the perinatal period produces long-term decreases in pain
      sensitivity (hypoalgesia) (Grunau et al., 1994a, 2001; Ren et al., 2004;
      LaPrairie and Murphy, 2007). To date, the mechanisms underlying these long-term
      adaptations, however, have yet to be elucidated. The present studies tested the
      hypothesis that neonatal inflammatory pain induces an upregulation in endogenous
      opioid tone that is maintained into adulthood, and that this increase in opioid
      tone provides the underlying mechanism for the observed hypoalgesia. On the day
      of birth (P0), inflammatory pain was induced in male and female Sprague-Dawley
      rats by intraplantar administration of carrageenan (CGN; 1%). In adulthood (P60),
      these animals displayed significantly increased paw withdrawal latencies in
      response to a noxious thermal stimulus in comparison to controls. Systemic
      administration of the brain-penetrant opioid receptor antagonist naloxone HCl,
      but not the peripherally restricted naloxone methiodide, significantly attenuated
      the injury-induced hypoalgesia. Direct administration of naloxone HCl or
      antagonists directed at the mu or delta opioid receptors into the midbrain
      periaqueductal gray (PAG) also significantly reversed the injury-induced
      hypoalgesia in adult rats. Parallel anatomical studies revealed that inflammatory
      pain experienced on the day of birth significantly increased beta-endorphin and
      met/leu-enkephalin protein levels and decreased opioid receptor expression in the
      PAG of the adult rat. Thus, early noxious insult produces long-lasting
      alterations in endogenous opioid tone, thereby profoundly impacting nociceptive
      responsiveness in adulthood.

PMID- 19862350
TI  - BETWEEN WOMEN'S RIGHTS AND MEN'S AUTHORITY: MASCULINITY AND SHIFTING DISCOURSES
      OF GENDER DIFFERENCE IN URBAN UGANDA.
AB  - Across the African continent, women's rights have become integral to
      international declarations, regional treaties, national legislation, and
      grassroots activism. Yet there is little research on how African men have
      understood these shifts, and how African masculinities are implicated in such
      changes. Drawing on a year of ethnographic research in the Ugandan capital
      Kampala, this article investigates how ordinary men and women in Uganda
      understand women's rights, and how their attitudes are tied to local conceptions
      of masculinity. I argue that a new configuration of gender relations is evident
      in urban Uganda-one that accommodates some aspects of women's rights while
      retaining previous notions of innate male authority. This article, therefore,
      illustrates the complex and often contradictory engagements with human rights
      that occur in local contexts, and how such engagements are shaped by gender
      relations, including conceptions of masculinity.

PMID- 19862349
TI  - Neuroimaging of aggressive and violent behaviour in children and adolescents.
AB  - In recent years, a number of functional and structural neuroimaging studies have
      investigated the neural bases of aggressive and violent behaviour in children and
      adolescents. Most functional neuroimaging studies have persued the hypothesis
      that pathological aggression is a consequence of deficits in the neural circuits
      involved in emotion processing. There is converging evidence for abnormal neural
      responses to emotional stimuli in youths with a propensity towards aggressive
      behaviour. In addition, recent neuroimaging work has suggested that aggressive
      behaviour is also associated with abnormalities in neural processes that subserve
      both the inhibitory control of behaviour and the flexible adaptation of behaviour
      in accord with reinforcement information. Structural neuroimaging studies in
      children and adolescents with conduct problems are still scarce, but point to
      deficits in brain structures in volved in the processing of social information
      and in the regulation of social and goal-directed behaviour. The indisputable
      progress that this research field has made in recent years notwithstanding, the
      overall picture is still rather patchy and there are inconsistencies between
      studies that await clarification. Despite this, we attempt to provide an
      integrated view on the neural abnormalities that may contribute to various forms
      of juvenile aggression and violence, and discuss research strategies that may
      help to provide a more profound understanding of these important issues in the
      future.

PMID- 19862351
TI  - Variational Bayesian identification and prediction of stochastic nonlinear
      dynamic causal models.
AB  - In this paper, we describe a general variational Bayesian approach for
      approximate inference on nonlinear stochastic dynamic models. This scheme extends
      established approximate inference on hidden-states to cover: (i) nonlinear
      evolution and observation functions, (ii) unknown parameters and (precision)
      hyperparameters and (iii) model comparison and prediction under uncertainty.
      Model identification or inversion entails the estimation of the marginal
      likelihood or evidence of a model. This difficult integration problem can be
      finessed by optimising a free-energy bound on the evidence using results from
      variational calculus. This yields a deterministic update scheme that optimises an
      approximation to the posterior density on the unknown model variables. We derive
      such a variational Bayesian scheme in the context of nonlinear stochastic dynamic
      hierarchical models, for both model identification and time-series prediction.
      The computational complexity of the scheme is comparable to that of an extended
      Kalman filter, which is critical when inverting high dimensional models or long
      time-series. Using Monte-Carlo simulations, we assess the estimation efficiency
      of this variational Bayesian approach using three stochastic variants of chaotic
      dynamic systems. We also demonstrate the model comparison capabilities of the
      method, its self-consistency and its predictive power.

PMID- 19862353
TI  - Imaging informatics for personalised medicine: applications and challenges.
AB  - Imaging informatics has emerged as a major research theme in biomedicine in the
      last few decades. Currently, personalised, predictive and preventive patient care
      is believed to be one of the top priorities in biomedical research and practice.
      Imaging informatics plays a major role in biomedicine studies. This paper reviews
      main applications and challenges of imaging informatics in biomedicine.

PMID- 19862355
TI  - The road to cancer control goes through leukemia research.

PMID- 19862354
TI  - Synergistic effects of metal ion and the pre-senile cataract-causing G98R alphaA
      crystallin: self-aggregation propensities and chaperone activity.
AB  - PURPOSE: alphaA- and alphaB-crystallins are abundantly present in the eye lens,
      belong to the small heat shock protein family, and exhibit molecular chaperone
      activity. They are also known to interact with metal ions such as Cu(2+), and
      their metal-binding modulates the structure and chaperone function. Unlike other
      point mutations in alphaA-crystallin that cause congenital cataracts, the G98R
      mutation causes pre-senile cataract. We have investigated the effect of Cu(2+) on
      the structure and function of G98R alphaA-crystallin. METHODS: Fluorescence
      spectroscopy and isothermal titration calorimetry were used to study Cu(2+)
      binding to alphaA- and G98R alphaA-crystallin. Circular dichroism spectroscopy
      was used to study secondary and tertiary structures, and dynamic light scattering
      was used to determine the hydrodynamic radii of the proteins. Chaperone activity
      and self-aggregation of the wild type and the mutant protein in the absence and
      the presence of the metal ions was monitored using light scattering. RESULTS: Our
      fluorescence quenching and isothermal titration calorimetric studies show that
      like alphaA-crystallin, G98R alphaA-crystallin binds Cu(2+) with picomolar range
      affinity. Further, both wild type and mutant alphaA-crystallin inhibit Cu(2+)
      induced generation of reactive oxygen species with similar efficiency. However,
      G98R alphaA-crystallin undergoes pronounced self-aggregation above a certain
      concentration of Cu(2+) (above subunit to Cu(2+) molar ratio of 1:3 in HEPES-NaOH
      buffer, pH 7.4). At concentrations of Cu(2+) below this ratio, G98R alphaA
      crystallin is more susceptible to Cu(2+)-induced tertiary and quaternary
      structural changes than alphaA-crystallin. Interestingly, Cu(2+) binding
      increases the chaperone-like activity of alphaA-crystallin toward the aggregation
      of citrate synthase at 43 degrees C while it decreases the chaperone-like
      activity of G98R alphaA-crystallin. Mixed oligomer formation between the wild
      type and the mutant subunits modulates the Cu(2+)-induced effect on the self
      aggregation propensity. Other heavy metal ions, namely Cd(2+) and Zn(2+) but not
      Ca(2+), also promote the self-aggregation of G98R alphaA-crystallin and decrease
      its chaperone-like activity. CONCLUSIONS: Our study demonstrates that unlike wild
      type alphaA-crystallin, G98R alphaA-crystallin and its mixed oligomers with wild
      type protein are vulnerable to heavy metal ions. Our study provides insight into
      aspects of how environmental factors could augment phenotype(s) in certain
      genetically predisposed conditions.

PMID- 19862356
TI  - Pretargeted radioimmunotherapy in the treatment of metastatic medullary thyroid
      cancer.

PMID- 19862357
TI  - The BC Cancer Agency Compassionate Access Program: outcome analysis of patients
      with esophagogastric cancer.
AB  - BACKGROUND: The BC Cancer Agency Gastro-intestinal Tumor Group supports one
      standard of care (SOC) chemotherapy regimen for metastatic esophagogastric
      adenocarcinoma-specifically, weekly cisplatin and 5-fluorouracil (5FU) infusion.
      All other regimens require Compassionate Access Program (CAP) approval for public
      funding. OBJECTIVES: We examined response, toxicity, and survival after first
      line cap chemotherapy (CAP1), or soc and second-line cap chemotherapy (CAP2).
      PATIENTS AND METHODS: We searched cap records for December 1999 to April 2006,
      abstracted charts, constructed a database, and undertook survival analyses.
      Treatment response, serious toxicities, and hospitalizations were recorded.
      RESULTS: We identified 32 esophageal (10 gastroesophageal junction) and 53
      gastric cancer (62%) patients, 55 of whom were stage M1 at diagnosis. Prior
      therapy consisted of chemoradiotherapy (n = 14), adjuvant chemotherapy (n = 3),
      and radical surgery (n = 34). Of these 85 patients, 50 received CAP1, and 35
      received soc, then CAP2. Docetaxel and irinotecan regimens accounted for 34% and
      36%, 5% and 55%, 16% and 32% respectively of first-, second-, and third-line cap
      requests. Partial responses were documented with soc (11/35, 31%) and CAP1 (6/50,
      12%). Grade 3+ toxicity rates were 19/50 (38%) and 6/35 (17%) with CAP1 and soc
      chemotherapy. With cap chemotherapy, 20 hospitalizations occurred, and with soc
      chemotherapy, 2 hospitalizations. For all patients, median follow-up and survival
      times were 8.9 months and 9.7 months respectively. LIMITATIONS: This is a
      retrospective analysis of patients deemed suitable to receive non-soc
      chemotherapy regimens or unsuitable to receive soc chemotherapy. CONCLUSIONS:
      Toxicities in cap chemotherapy regimens were substantial. Survival times were
      consistent with results of international phase II and III trials in
      esophagogastric cancer.

PMID- 19862358
TI  - Workplace support for employees with cancer.
AB  - OBJECTIVE: The aim of the present study was to survey human resources personnel
      about how their northeastern Ontario workplaces assist employees with cancer.
      STUDY DESIGN AND SETTING: This cross-sectional study was conducted from December
      2007 to April 2008. Surveys were sent to 255 workplaces in northeastern Ontario
      with 25 or more employees, and 101 workplaces responded (39.6% response rate).
      Logistic regression modelling was used to identify factors associated with more
      or less workplace support. More or less workplace support was defined by
      provision of paid time to employees with medical appointments and an offer of a
      return-to-work meeting and reduced hours for employees with cancer. Factors
      considered in the model included organization size, geographic location (urban,
      rural), and workplace type (private sector, public sector). RESULTS: Most of the
      human resources staff who completed the surveys were women (67.4%), and
      respondents ranged in age from 25 to 70 years (mean: 45.30 +/- 8.10 years).
      Respondents reported working for organizations that ranged in size from 25 to
      more than 9000 employees. In the logistic regression model, large organization
      size [odds ratio (or): 6.97; 95% confidence interval (ci): 1.34 to 36.2] and
      public sector (or: 4.98; 95% ci: 1.16 to 21.3) were associated with employer
      assistance. Public sector employers provided assistance at a rate 5 times that of
      private sector employers, and large organizations (>50 employees) provided
      assistance at a rate 7 times that of smaller organizations. CONCLUSIONS: In the
      population studied, employees with cancer benefit from working in larger and
      public sector organizations. The data suggest a need for further support for
      employees with cancer in some other organizations.

PMID- 19862359
TI  - Preparation with recombinant humanized thyroid-stimulating hormone before
      radioiodine ablation after thyroidectomy: a systematic review.
AB  - BACKGROUND: Standard treatment for differentiated thyroid cancer is thyroidectomy
      followed in selected cases by radioiodine ablation (RA). Recombinant humanized
      thyroid-stimulating hormone (rhTSH) is an exogenous source of tsh that can be
      administered to obviate the need for hormone withdrawal. In this systematic
      review, we analysed the evidence for the therapeutic use of (rhTSH for RA
      preparation. METHOD: A systematic review of the MEDLINE and EMBASE databases from
      1996 through January 2008 selected articles reporting randomized controlled
      trials, cohort studies, and retrospective studies published in English that
      compared ra using rhTSH with standard hormone withdrawal. RESULTS AND
      INTERPRETATION: Stimulation by rhTSH is equivalent to thyroid hormone withdrawal
      in achieving ablation while avoiding detrimental symptoms of hypothyroidism and
      significantly lowering the whole-body radiation dose. Furthermore, rhTSH may be
      the only option for patients who either cannot raise endogenous tsh or who would
      be at risk from the morbidity of hypothyroidism. Based on the results of
      validated instruments of physical and mental performance, there is agreement that
      rhTSH maintains a better quality of life. Studies of cost-effectiveness found
      that rhTSH-prepared patients lost less time from work and required fewer
      encounters with health care providers.

PMID- 19862360
TI  - I-Tositumomab in lymphoma.
AB  - Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target
      radiation specifically to sites of lymphoma involvement. Initial studies of
      (131)I-tositumomab in non-Hodgkin lymphoma (NHL) have suggested benefit in
      patients with relapsed or refractory indolent disease. However, the routine
      adoption of this agent is tempered by concerns about associated toxicities and
      unclear long-term benefit. Based on a comprehensive search for studies on (131)I
      tositumomab use in lymphoma, this systematic review summarizes and evaluates the
      evidence on the benefits and risks of this novel therapy,the predictors for
      response and toxicity, and the role of dosimetry and imaging studies before
      treatment.We identified 18 trials investigating the use of (131)I-tositumomab for
      the treatment of adult patients with nhl. In trials of patients with relapsed or
      refractory indolent nhl, overall response rates ranged from 67% to 83%. In
      patients with follicular nhl refractory to the monoclonal antibody rituximab,
      response rates remained high (65%-72%). However, in rituximab-naive patients with
      relapsed or refractory indolent or transformed nhl, improvements in time to
      progression or survival have not been clearly established. (131)I-Tositumomab is
      an active agent in relapsed and refractory non-Hodgkin lymphoma that should be
      considered in selected patients.

PMID- 19862361
TI  - The role of neoadjuvant (HER)2-targeted therapies in (HER)2-overexpressing breast
      cancers.
AB  - Women receiving neoadjuvant systemic therapy for primary operable or inoperable
      breast cancer can potentially benefit in a number of ways, but the main
      advantage, which has been consistently demonstrated, is improved tumour
      resectability. Given the improvement in outcomes with the adjuvant use of
      trastuzumab in patients with early-stage breast cancer positive for the human
      epidermal growth factor receptor 2 (HER2), questions have been raised about the
      use of trastuzumab in the neoadjuvant setting. The present paper reviews the
      currently available data and outlines suggestions from a panel of Canadian
      oncologists about the use of trastuzumab and other HER2-targeted agents in the
      neoadjuvant setting.The panel focussed on the use of trastuzumab and other HER2
      targeted agents as neoadjuvant therapy in primary operable, locally advanced, and
      inflammatory breast cancer; and possible choices of chemotherapeutic regimens
      with trastuzumab.The suggestions described here will continue to evolve as data
      from current and future trials with trastuzumab and other HER2-targeted agents
      emerge.

PMID- 19862362
TI  - Radiation treatment waiting times for breast cancer patients in Manitoba, 2001
      and 2005.
AB  - INTRODUCTION: Our study examined the wait time from ready-to-treat to radiation
      therapy for cohorts of breast cancer patients requiring adjuvant radiation
      therapy in 2001 and in 2005 after the implementation of strategies to reduce wait
      times for radiation treatment. We also examined the overall time from diagnosis
      to radiation treatment and whether distance from the cancer treatment centre or
      month of referral had an effect on wait times. METHODS: This population-based
      retrospective study looked at representative samples of women newly diagnosed
      with breast cancer in 2001 and 2005. Patients who required radiation treatment to
      the breast or chest wall were followed from first contact to the start of
      radiation treatment. RESULTS: Time from ready-to-treat to first radiation
      treatment was significantly reduced for patients in 2005 as compared with 2001,
      regardless of whether chemotherapy was administered before radiation treatment.
      Time from diagnosis to radiation treatment was not different by year for those
      who received radiation only. Time from diagnosis to chemotherapy was
      significantly longer in 2005. No effect of month of diagnosis on wait times was
      observed. INTERPRETATION: A significant improvement in the median wait time from
      ready-to-treat to first radiation treatment was noted from 2001 to 2005. This
      improvement may be attributable to measures taken to reduce such waits. However,
      we observed an increase in the median time from diagnosis to referral and from
      referral to consultation with medical or radiation oncology (or both), so that
      the overall time from diagnosis to radiation treatment was not different.
      Although specific intervals related to radiation treatment delivery were
      improved, the entire trajectory of breast cancer care experienced by patients
      needs to be considered.

PMID- 19862363
TI  - Factors influencing mammography participation in Canada: an integrative review of
      the literature.
AB  - This integrative review critically examines quantitative and qualitative evidence
      concerning factors influencing the participation of Canadian women in
      mammography. Empirical studies published between 1980 and 2006 were identified
      and retrieved by searching electronic databases and references listed in
      published studies. Among the 1461 citations identified and screened, 52 studies
      met the inclusion criteria and were independently appraised by two researchers.
      Extracted data were categorized, summarized, compared, and interpreted within and
      across studies. The presentation of barriers and facilitators to mammography was
      guided by the Pender Health Promotion Model. Findings from this review showed
      that no published studies were specific to settings in Saskatchewan, Nova Scotia,
      Prince Edward Island, Newfoundland and Labrador, and the three Canadian
      territories. The most common barriers to screening were membership in an ethnic
      minority and concerns about pain, radiation, and embarrassment. The
      recommendation of a health care provider for mammography was found to be the most
      common facilitator for the engagement of women in this health behaviour. The
      targeting of specific strategies aimed at overcoming identified barriers and the
      enhancement of facilitators are essential to improving mammography participation
      rates throughout Canada.

PMID- 19862365
TI  - Response to 5-fluorouracil in metastatic extramammary Paget disease of the
      scrotum presenting as pancytopenia and back pain.
AB  - Extramammary Paget disease is a rare intraepithelial neoplasm of the vulvar,
      penoscrotal, or perianal skin. No effective therapies for metastatic disease have
      been reported, and prognosis for metastatic disease is poor.Here, we report the
      case of an Asian man who was initially diagnosed with extramammary Paget disease
      of the scrotum. Three years later, the patient presented to hospital with
      pancytopenia and back pain. After an extensive work-up, biopsies of liver and
      bone marrow revealed adenocarcinoma with signet cells and immunohistochemical
      staining positive for keratin 7, carcinoembryonic antigen, and prolactin-induced
      protein, but negative for keratin 20, S100, and prostate markers, consistent with
      his previous biopsyproven Paget disease of the scrotum. The patient was treated
      with 5-fluorouracil-based therapy in addition to palliative radiotherapy to
      selected spine levels. A promising palliative response was demonstrated following
      5-fluorouracil chemotherapy.A review of the literature on the pathogenesis,
      diagnosis, treatment options, and outcomes for metastatic extramammary Paget
      disease is presented.

PMID- 19862364
TI  - Isolated colorectal liver metastases locally progressing after stereotactic body
      radiotherapy rescued with surgery.
AB  - Treatment of patients with metastatic colorectal cancer has changed in recent
      years, with many patients now being offered intent-to-treat regimens. In this
      context, a multidisciplinary approach to the metastatic disease may lead to
      individualized treatment for any patient. Stereotactic body radiotherapy (SBRT)
      is not the most common treatment. Here, we present the clinical case of a patient
      with a solitary liver metastasis initially treated with SBRT that was rescued
      with surgery when a local recurrence was detected.

PMID- 19862366
TI  - Efficacy of third-line therapy using bevacizumab in a patient with metastatic
      colorectal cancer.
AB  - Bevacizumab is currently approved in association with first- and second-line 5
      fluorouracil-based chemotherapy regimens for patients with metastatic colorectal
      cancer. Few data about the usefulness of bevacizumab in third-line settings are
      available. We describe a patient refractory to FOLFIRI and FOLFOX chemotherapy
      regimens who showed a dramatic and durable response to bevacizumab and FOLFIRI.
      We also review and discuss the available literature.

PMID- 19862367
TI  - Resolution of severe oncogenic hypophosphatemic osteomalacia after resection of a
      deeply located soft-tissue tumour.
AB  - Oncogenic osteomalacia is a rare metabolic bone disease characterized by
      phosphate leakage from the kidney and subsequent hypophosphatemia. It is caused
      by a phosphaturic factor produced by certain tumours. Removal of such tumours can
      completely cure the condition. Here, we report the case of a patient who was
      crippled with oncogenic osteomalacia. Extensive study revealed a tumour deeply
      located in the pelvis; removal of the tumour resulted in complete recovery. The
      tumour was identified as a mesenchymal tumour (mixed connective-tissue variant).
      The diagnostic evaluation, differential diagnosis, and treatment are discussed.

PMID- 19862369
TI  - Cancer pain--come so far, but so far to go!

PMID- 19862370
TI  - Cancer pain--progress and ongoing issues in Africa.

PMID- 19862371
TI  - Prevalence and correlates of pain in the Canadian National Palliative Care
      Survey.
AB  - BACKGROUND: Pain is a common problem for people with cancer who are nearing the
      ends of their lives. OBJECTIVE: In the present multicentre Canadian study of
      palliative cancer care, the prevalence of pain, its perceived severity and its
      correlates across a range of physical, social, psychological, and existential
      symptoms and concerns were examined. METHODS: Semistructured interviews were
      conducted with 381 patients. In addition to inquiring about pain, the interview
      also assessed 21 other symptoms and concerns, and collected information about
      demographic characteristics, functional status and medication use. RESULTS: Pain
      of any intensity was reported by 268 (70.3%) participants, although for 139
      (36.5%), the severity was rated as minimal or mild. For 129 (33.9%) individuals,
      pain was reported as moderate to extreme, and considered by the respondents to be
      an important ongoing problem. Patients who reported moderate to extreme pain were
      younger than other participants, but had lower functional status and a shorter
      median survival duration. They were more likely than other participants to be
      treated with opioid medications (P<0.001) and, less reliably, with
      benzodiazepines (P=0.079). Compared with participants with no, minimal or mild
      pain, those with moderate to extreme pain had a higher prevalence of distressing
      problems on 11 of 21 other symptoms and concerns. The strongest correlations were
      with general malaise (rho = 0.44), suffering (rho = 0.40), nausea (rho = 0.34),
      weakness (rho = 0.31), drowsiness (rho = 0.29) and anxiety (rho = 0.29).
      CONCLUSIONS: Pain continues to be a difficult problem for many patients who are
      receiving palliative cancer care, particularly younger individuals who are
      nearing death.

PMID- 19862372
TI  - Intrathecal infusions for intractable cancer pain: a qualitative study of the
      impact on a case series of patients and caregivers.
AB  - BACKGROUND: The need for intrathecal infusion in a palliative care setting is
      infrequent. Despite established efficacy, safety and cost effectiveness, this is
      considered an 'extraordinary measure' in Canada. Patients requiring this approach
      are not typical palliative care patients, having shorter and more uncertain life
      expectancies. OBJECTIVES: The present study is a qualitative exploration of the
      impact of intrathecal pump implantation on cancer patients, and also the impact
      of the intervention on the staff caring for those patients. METHODS: Palliative
      care unit patients who received an implanted intrathecal pump or dome catheter
      for intractable cancer pain participated in multiple semistructured interviews.
      Doctors and nurses caring for each patient were also interviewed. Interviews were
      recorded and analyzed for themes. The study terminated when saturation was
      reached. RESULTS: Six patients participated, with up to three interviews each.
      Twenty-four staff interviews took place. Patients' hopes and expectations were
      not always fully met, but the infusions had a profound positive effect on quality
      of life. Patients expressed anxiety about dependence on the device, and also on a
      few highly skilled individuals. Staff interviews revealed a significant impact on
      the 'culture' of the palliative care unit. Clear communication of the rationale
      for infusion was very important, as was regular education about infusion
      management. CONCLUSIONS: Implanted intrathecal infusion devices are a necessary
      part of a tertiary level cancer pain management service for the unfortunate
      minority with intractable pain. Practical recommendations for care are made for
      palliative care programs contemplating offering intrathecal infusions.

PMID- 19862391
TI  - Casting ability of selected impression materials tested in different conditions
      in an in vitro sulcus model.
AB  - OBJECTIVE: To test casting capacities of impression materials under dry and wet
      sulcular conditions in vitro. METHOD AND MATERIALS: An incisor with a circular
      shoulder preparation (1 mm) was inserted in a primary mold. A shiftable secondary
      mold allowed adaptation of sulcular depth (1 to 4 mm). An outer circular chamfer
      assured reproducible positioning of an impression material carrier. Tested
      materials were PVS of differing viscosities (extra low, Panasil Contact Plus
      [ELV]; low, Affinis Light Body [LV]; and medium, Virtual Monophase [MV]) and one
      polyether material of low viscosity (Permadyne Garant [PE]). Impressions were
      made with sulcular depths of 1 to 4 mm in wet and 1 and 4 mm in dry conditions,
      cut in half, and digitized with a light microscope (Stemi SV8). Surface area of
      the region of interest (ROI, at inner angle of preparation) was determined with
      Optimas 6.2. Medians were calculated, and statistical analysis was performed
      using the Mann-Whitney U test (P # .05). RESULTS: Median values of the
      measurements under wet condition demonstrated the smallest ROI areas for the ELV
      (297-330[pixel]) and the MV (253-421[pixel]) materials followed by the LV (582
      745[pixel]) and the PELV (544-823[pixel]). All materials showed significantly
      higher values for the wet compared to dry sulcular conditions. Repeated
      measurements showed no significant differences to the corresponding first
      determined series. CONCLUSION: The sulcus model is applicable to assess casting
      abilities of impression materials in clinically approximated sulcular conditions.
      The PVS materials with extra low and medium viscosities showed the best
      properties in dry and wet conditions.

PMID- 19862373
TI  - Use of lidocaine patches for neuropathic pain in a comprehensive cancer centre.
AB  - BACKGROUND: There are few reports of the use of the lidocaine 5% patch (L5%P) for
      neuropathic pain (NP) in the cancer patient. Within a comprehensive cancer
      centre, L5%P has been prescribed by the Pain and Palliative Care Service (Peter
      McCallum Cancer Centre, East Melbourne, Victoria, Australia) for selected
      patients with NP since 2001. OBJECTIVE: To retrospectively audit the use of L5%P
      within a comprehensive cancer centre. METHODS: All L5%P prescriptions up to
      January 2009 were listed and patient medical records were searched to determine
      neuropathic pain syndromes treated, the presence of allodynia, previous analgesic
      medications, treatment duration and outcome. RESULTS: L5%P was prescribed for 97
      patients, most frequently for persistent postsurgical NP (n=26), postherpetic
      neuralgia (n=24) and cancer-related NP (n=18). Six patients had no history of
      cancer and two patients never applied L5%P. Reviewers classed L5%P analgesic
      efficacy as 'potent' in 38% of patients with postherpetic neuralgia, 35% of
      patients with postsurgical pain, 27% of patients with NP after other treatments
      for cancer and 12% of patients with NP attributed to cancer alone. Allodynia
      featured in at least 60% of patients. Where allodynia was present, the efficacy
      of L5%P was assessed as 'potent' in 38% and 'partial' in 24%, but 'ineffective'
      in 26%, and 'causing worse pain' in 3.4% of patients. Treatment duration extended
      longer than one month in 52 patients, longer than two months in 29 patients and
      longer than one year in 13 patients. Therapy was ceased due to skin irritation in
      seven patients. The outcomes in relation to other reports are discussed.
      CONCLUSION: The present data support trials of L5%P for cancer patients with NP
      syndromes associated with allodynia.

PMID- 19862392
TI  - A comparison between conventional visual and spectrophotometric methods for shade
      selection.
AB  - OBJECTIVE: Inconsistencies among dentists in matching natural tooth shades have
      been documented. This study examined the reliability of a spectrophotometer in
      shade selection compared to visual method. METHOD AND MATERIALS: Nine observers
      with normal color vision were asked to visually and digitally match shades of
      nine maxillary models with incisors being replaced by Vita Classical shade guide
      tabs. The same test was carried out in vivo on nine subjects' maxillary central
      incisors. Observers included prosthodontists, dental technicians, and
      postgraduate students. RESULTS: No significant difference was found among
      observers in shade selection regardless of the selection method. However, there
      was a significant difference between digital and visual methods in shade
      selection. Digital method was five times more likely to match the original shade
      color compared to visual method. CONCLUSION: The system does not solve all
      problems involved in the determination of a tooth shade. Vita Easyshade
      spectrophotometer was more likely to match the shade compared to visual method.
      Nevertheless, this system needs further refinement, as well as software upgrades.
      Shade-matching devices could help clinicians and technicians achieve a better
      shade choice. The combination of visual shade analysis and digital shade
      measurement together lies in the precise predictability of the miscibility of
      shades.

PMID- 19862393
TI  - Dentistry-first and foremost a discipline promoting oral health.

PMID- 19862394
TI  - In Memoriam: Dr John W. McLean 1925-2009.

PMID- 19862396
TI  - Masking of labial enamel white spot lesions by resin infiltration--a clinical
      report.
AB  - This article describes a novel approach to treat smooth-surface white spot
      lesions micro-invasively. The technique is based on the infiltration of enamel
      caries lesions with low-viscosity light-curing resins called infiltrants. After
      the surface layer is eroded, the lesions are desiccated and a resin infiltrant is
      applied. The resin penetrates into the lesion micro-porosities driven by
      capillary forces and is subsequently hardened. Infiltrated lesions lose their
      whitish appearance and look similar to sound enamel. Additionally, the treatment
      prevents lesion progression. The proposed technique might be an alternative to
      microabrasion and restorative treatment, in particular for white spot lesions of
      esthetically relevant teeth.

PMID- 19862397
TI  - Intraoral contact mucositis induced by cinnamon-flavored chewing gum--a case
      report.
AB  - Contact mucositis is an inflammatory mucosal reaction caused by many agents. A
      case of a 53-year-old man with contact-type allergy in oral mucosa due to
      cinnamon chewing gum is presented. This condition should be considered in the
      differential diagnosis of nonspecific oral lesions.

PMID- 19862398
TI  - Integrated clinical treatment of gingival recession secondary to root
      perforation: case report.
AB  - Among the factors that influence the success of treatment of a root perforation,
      its location and possibility of contamination are determinant because the
      interaction of these 2 factors may result in significant periodontal injury. The
      management of cases of hard-to-reach contaminated perforations depends on the
      choice of an adequate technique. In the case reported in this article, controlled
      orthodontic tooth extrusion was successfully performed to treat gingival
      recession secondary to root perforation. The outcomes showed that this technique
      preserves the zone of attached gingiva, maintains the crown height, and prevents
      the involvement of the supporting bone tissue. The favorable clinical and
      radio?graphic conditions after 7 years of follow-up demonstrate the viability of
      this treatment approach.

PMID- 19862399
TI  - Influence of overlay restorative materials and load cusps on the fatigue
      resistance of endodontically treated molars.
AB  - OBJECTIVES: To assess the influence of restorative materials and load cusps on
      the fatigue resistance of endodontically treated molars. METHOD AND MATERIALS:
      Thirty extracted molars received root canal treatment followed by a standardized
      tooth preparation (3-mm cuspal reduction and immediate dentin sealing). Twenty
      Cerec 3 overlays (Sirona Dental Systems) were milled in the ceramic Vita MKII
      block (Vident; groups MKIIGL and MKIIGL-Z, oven-glazed), and 10 restorations were
      duplicated with a composite resin (Miris 2, Coltane/Whaledent; group M2). The
      fitting surfaces of the restorations were hydrofluoric acid etched (porcelain
      only) and silanated. Preparations were airborne-particle abraded and etched. All
      restorations were luted with preheated Filtek Z100 (3M ESPE) and subjected to
      cyclic isometric chewing (5 Hz) starting at 200 N (5,000 cycles), followed by
      stages of 400, 600, 800, 1,000, 1,200, and 1,400 N at a maximum of 30,000 cycles
      each. A stainless steel load sphere was used for groups MKIIGL and M2, while a
      composite resin load sphere was used in group MKIIGL-Z. All samples were loaded
      until fracture or to a maximum of 185,000 cycles. Groups were compared using the
      Kaplan-Meier survival curves (P = .05). RESULTS: None of the molars restored with
      porcelain withstood all 185,000 loading cycles (survival = 0%). The mean fracture
      load for MKIIGL was 1,060 N and for MKIIGL-Z, 1,280 N. In group M2, the survival
      rate was 50%. The rate of fracture below the CEJ was 40%, 30%, and 20% for
      MKIIGL, MKIIGL-Z, and M2, respectively. CONCLUSION: Miris 2 overlays showed
      higher fatigue resistance than MKII porcelain (P = .01) when loaded with a
      stainless steel antagonist.

PMID- 19862400
TI  - Endoscopic root canal treatment.
AB  - OBJECTIVE: To describe an innovative endoscopic technique for root canal
      treatment. MATERIALS AND METHODS: Root canal treatment was performed on 12
      patients (15 teeth), using a newly developed endoscope (Sialotechnology), which
      combines an endoscope, irrigation, and a surgical microinstrument channel.
      RESULTS: Endoscopic root canal treatment of all 15 teeth was successful with
      complete resolution of all symptoms (6-month follow-up). CONCLUSION: The novel
      endoscope used in this study accurately identified all microstructures and
      simplified root canal treatment. The endoscope may be considered for use not only
      for preoperative observation and diagnosis but also for active endodontic
      treatment.

PMID- 19862401
TI  - The effect of finish line curvature on marginal fit of all-ceramic CAD/CAM crowns
      and metal-ceramic crowns.
AB  - OBJECTIVES: To investigate the effect of abutment finish line curvature on the
      fit of all-ceramic CAD/CAM crowns and metal-ceramic crowns. METHOD AND MATERIALS:
      Three types of finish line curvature abutments (1-, 3-, and 5-mm curvature) were
      prepared on typodont maxillary central incisors. For each type of abutment, 5 all
      ceramic crowns (Cercon system, DeguDent) and 5 metal-ceramic crowns were
      fabricated. The marginal gaps of copings and veneered crowns were measured on a
      profile projector. The data were calculated and analyzed with 2-way ANOVA and
      Tukey HSD test (alpha = .05). RESULTS: The mean labial, lingual, mesial, and
      distal marginal gaps (SD) of all-ceramic crowns were similar: respectively, 54
      (10), 51 (11), 47 (13), and 49 (9) microm for 1-mm curvature; 49 (12), 53 (11),
      54 (10), and 55 (12) microm for 3-mm curvature; and 57 (12), 54 (11), 53 (10),
      and 52 (9) microm for 5-mm curvature. The mean labial, lingual, mesial, and
      distal marginal gaps (SD) of metal-ceramic crowns were 36 (7), 41 (9), 26 (8),
      and 28 (10) microm, respectively, for 1-mm curvature. The mean labial and lingual
      marginal gaps (SD) of metal-ceramic crowns for 3-mm curvature were 45 (8) and 48
      (9) microm, respectively-significantly larger than mesial (P = .01 and .007) and
      distal (P = .03 and .02) gaps. The mean labial and lingual marginal gaps (SD) of
      metal-ceramic crowns for 5-mm curvature were 76 (10) and 74 (15) microm,
      respectively-significantly larger than mesial (P = .001 and .001) and distal (P =
      .001 and .001) gaps. CONCLUSIONS: The abutment finish line curvature had no
      significant effect on the marginal fit of all-ceramic crowns, but had a
      significant effect on the marginal fit of metal-ceramic crowns.

PMID- 19862402
TI  - Influence of anatomic features on the effectiveness of enamel matrix derivative
      proteins in the treatment of proximal Class II furcation involvements.
AB  - OBJECTIVES: To evaluate the influence of furcation anatomy and bone defect
      morphology on the treatment of Class II proximal furcations treated with enamel
      matrix derivative (EMD) proteins. METHOD AND MATERIALS: Eighteen Class II
      proximal furcations were treated with open-flap debridement + 24% EDTA
      conditioning + EMD proteins. Probing depth, gingival margin position, relative
      vertical and horizontal clinical attachment level, and vertical and horizontal
      bone levels were evaluated immediately before and 6 months after the surgeries.
      The changes in these parameters were correlated with vertical defect depth,
      number of walls, depth defect, interdental distance, root divergence, furcation
      distance, horizontal measure, root trunk, and furcation height, using the Pearson
      and Spearman rank correlation tests (a = 5%). RESULTS: The depth defect
      correlated with gingival margin position (r = 0.52; P = .03), probing depth (r =
      0.63; P = .005), and horizontal bone level (r = -0.46; P = .05). The furcation
      height also correlated with gingival margin position (r = 0.53; P = .02) and
      horizontal bone level (r = -0.57; P = .01). Moreover, the number of walls of
      vertical defect positively influenced relative vertical clinical attachment level
      (r = 0.47; P = .05). CONCLUSIONS: Within the limits of this study, furcation
      anatomy and defect morphology influence the clinical response of EMD protein
      therapy in Class II proximal furcation involvements.

PMID- 19862403
TI  - Effect of adhesive agent and fissure morphology on the in vitro microleakage and
      penetrability of pit and fissure sealants.
AB  - OBJECTIVE: To evaluate the effect of adhesive agents and fissure morphology on
      the microleakage and penetrability of pit and fissure sealants. METHOD AND
      MATERIALS: Sealants used in this study included Aegis (Bosworth), conseal f
      (Southern Dental Industries), and Admira Seal (Voco). Adhesive agents included
      Optibond Solo Plus (sds/Kerr) and Clearfil S3Bond (Kuraray). Ninety extracted
      permanent molars were randomly assigned to 9 groups combining sealant and
      adhesive agent materials. A sealant and control group (phosphoric acid etch only)
      was also included. Dye penetration (microleakage), penetrability, and fissure
      morphology assessment was performed for the treatment groups through microscopic
      evaluation. RESULTS: Significant (P = .003) differences in microleakage were
      exhibited, with the Aegis + control and Aegis + Optibond Solo Plus groups
      displaying less leakage, while significant (P = .03) differences were also noted
      between groups regarding penetrability. Fissure morphology was not a significant
      (P = .82) factor affecting microleakage; however, fissure type did significantly
      (P < .001) impact penetrability. No correlation was found between the extent of
      microleakage and penetrability. CONCLUSION: Application of sealants using
      phosphoric acid as a conditioning agent revealed superior results, while the use
      of adhesives was found to be unnecessary.

PMID- 19862404
TI  - Implant treatment planning in fresh extraction sockets: use of a novel
      radiographic guide and CAD/CAM technology.
AB  - Diagnosis and implant treatment planning in cases where hopeless teeth need to be
      extracted and immediately replaced with implants are more difficult and
      challenging than a standard multistage approach. Software and CAD/CAM
      technologies are becoming increasingly common to help clinicians in their
      practices. They use data from CT scans of the patient and of a radiographic guide
      for virtual implant treatment planning on a computer and the successive
      production of a surgical template, which will facilitate surgery and enable
      fabrication of a prosthesis to be delivered immediately. These procedures,
      however, are well-established only for patients who are already edentulous in the
      area to be treated; they are difficult to apply to a patient whose desire is to
      keep the hopeless dentition until the day of implant surgery to avoid having to
      wear a removable partial or complete denture. This article describes the
      advantages and the technique for fabrication of a novel 2-piece radiographic
      guide that, in conjunction with CAD/CAM technology, will help clinicians in the
      diagnosis and implant treatment planning of patients who want to retain their
      teeth until surgery.

PMID- 19862405
TI  - Effect of finishing and polishing procedures on surface roughness of tooth
      colored materials.
AB  - OBJECTIVES: To evaluate the effect of 2 polishing systems on surface roughness of
      tooth-colored restorative materials. METHOD AND MATERIALS: The materials included
      3 flowable resins (Admira Flow, Voco; Dyract Flow, Dentsply; Filtek Flow, 3M
      ESPE) and a micro?hybrid composite resin (Filtek Z250, 3M ESPE). Eighteen
      specimens of each material were prepared using a Plexiglas well covered by a
      Mylar strip (10 mm in diameter and 2 mm in depth). The Ra (baseline) was measured
      with a Mitutoyo Surftest-402 Surface Roughness Tester (Mitutoyo) with a standard
      cut-off value of 0.8 mm. Five tracings at different locations on each specimen
      were made. The specimens were then randomly divided into two finishing and
      polishing groups (n = 9): (1) Sof-Lex Pop-on disks (3M ESPE), and (2) Astropol
      and Astrobrush system (Ivoclar Vivadent). After finishing and polishing, surface
      roughness of the specimens was remeasured. Data were analyzed using 1- and 2-way
      ANOVA, at P < .05. RESULTS: The Mylar strip produced the smoothest surface in all
      restorative materials, while 2-way ANOVA demonstrated a significant difference
      for the finishing and polishing procedures (P = .000). The smoothest surface was
      generated with Sof-Lex Pop-on disks for all the materials tested. In procedure 2
      (diamond bur/Astropol and Astrobrush system), Admira Flow group received the
      highest average surface roughness value, and a significant difference was
      revealed between Admira Flow and the other resins (P = .001). CONCLUSION: Sof-Lex
      Pop-on disks produced a smoother surface than Astropol and Astrobrush silicone
      polishers for microhybrid and flowable composites.

PMID- 19862408
TI  - The sunny side of chemistry: green synthesis by solar light.
AB  - The storage of solar energy is one of the main challenges in the near future. A
      rather unexploited way to fulfil this goal is the solar light induced formation
      of new chemical bonds, i.e. the synthesis of chemicals. Solar photons can be
      considered the ideal green reagents since they are costless and leave no residue
      in the reaction mixture. In many cases the solar radiation could be successfully
      used in place of toxic or expensive chemical reagents to overcome the activation
      energy in organic synthesis. In this perspective, the emerging trends on the use
      of solar light for green synthesis are summarized, highlighting the advantages of
      this photochemical method.

PMID- 19862409
TI  - Time-resolved methods in biophysics. 10. Time-resolved FT-IR difference
      spectroscopy and the application to membrane proteins.
AB  - The introduction of time-resolved Fourier transform infrared (FT-IR) spectroscopy
      to biochemistry opened the possibility of monitoring the catalytic mechanism of
      proteins along their reaction pathways. The infrared approach is very fruitful,
      particularly in the application to membrane proteins where NMR and X-ray
      crystallography are challenged by the size and protein hydrophobicity, as well as
      by their limited time-resolution. Here, we summarize the principles and
      experimental realizations of time-resolved FT-IR spectroscopy developed in our
      group and compare with aspects emerging from other laboratories. Examples of
      applications to retinal proteins and energy transduction complexes are reviewed,
      which emphasize the impact of time-resolved FT-IR spectroscopy on the
      understanding of protein reactions on the level of single bonds.

PMID- 19862410
TI  - A micropatterned cell array with an integrated oxygen-sensitive fluorescent
      membrane.
AB  - We propose a simple method for producing micropatterned cell spots by
      photocatalytic lithography on a Pt porphyrin-based oxygen-sensitive polystyrene
      membrane that enables real-time imaging of oxygen consumption of patterned cell
      spots with sub-millimetre resolution.

PMID- 19862411
TI  - A novel molecular conjugate for the simultaneous DNA oxidation and targeted
      delivery of nitric oxide triggered by light.
AB  - We have designed and synthesized a novel photoactivable molecular conjugate
      integrating three basic components in its molecular skeleton: a DNA intercalator,
      a viologen moiety and a nitric oxide (NO) photodonor. This compound is soluble in
      aqueous solution and binds to double strand DNA with an association constant of
      1.1 x 10(4) M(-1). The fluorescence of the intercalator unit is strongly quenched
      due to an intramolecular electron transfer involving the adjacent viologen
      moiety. Laser flash photolysis measurements provide direct evidence that, in the
      presence of DNA, this process is followed by a second electron transfer from DNA
      to the oxidized intercalator, leading to nucleobase oxidation. Also, the light
      absorbed by the NO photodonor results in the simultaneous release of NO nearby
      DNA as confirmed by the direct monitoring of this transient species through an
      ultrasensitive NO electrode. In this view, this conjugate represents an
      intriguing model system for photoactivable "dual-function" compounds for
      biomedical research.

PMID- 19862412
TI  - The photosensitizing activity of lumazine using 2'-deoxyguanosine 5'
      monophosphate and HeLa cells as targets.
AB  - Lumazines are an important family of heterocyclic compounds present in biological
      systems as biosynthetic precursors and/or products of metabolic degradation. Upon
      UV irradiation, the specific compound called lumazine (pteridine-2,4(1,3H)-dione)
      is able to generate singlet oxygen (1O2), which is one of the main chemical
      species responsible for photodynamic effects. To further assess the
      photosensitizing capability of lumazine (Lum) experiments were performed using
      the nucleotide 2'-deoxyguanosine 5'-monophosphate (dGMP) and, independently,
      cervical cancer cells (HeLa cell line) as targets. In the dGMP experiments, the
      data revealed that dGMP indeed undergoes oxidation/oxygenation photoinduced by
      Lum. Moreover, dGMP disappearance proceeds through two competing pathways: (1)
      electron transfer between dGMP and excited-state Lum (Type I process) and (2)
      reaction of dGMP with 1O2 produced by Lum (Type II process). The multistep
      processes involved are convoluted and susceptible to changes in experimental
      conditions. The independent studies with HeLa cells included fluorescence
      analysis of cell extracts and phototoxicity experiments performed at the single
      cell level. Results showed that, upon Lum uptake and irradiation, photodynamic
      effects occur. In particular, the mitochondria and cell membrane were perturbed,
      both of which reflect key stages in cell death. The data reported herein
      illustrate how the irradiation of an endogenous biological compound can have
      various effects which, depending on the system, can be manifested in different
      ways.

PMID- 19862413
TI  - Experimental and quantum chemical study of photochemical properties of 4
      hydroxyquinoline.
AB  - UV irradiation of aqueous 4-hydroxyquinoline (4HQN) solutions results in the
      formation of the triplet states with the quantum yields 30%, 35%, and 7.5% in
      acidic, neutral, and basic solutions, respectively. In neutral solutions, the
      keto form is the major tautomeric structure for ground, excited singlet and
      triplet states of 4HQN. Triplet 4HQN reacts with amino acids tryptophan and
      tyrosine and with antioxidant ascorbate via the mechanism of electron transfer.
      The individual experimental and calculated UV-Vis spectra of different acid-base
      forms of 4HQN in the ground and triplet excited states, as well as reduced and
      oxidized forms of 4HQN, are reported. Under intense laser irradiation 4HQN
      undergoes biphotonic ionization, the excited singlet state being the precursor
      for photoionization.

PMID- 19862415
TI  - Photopolymerization of conductive polymeric metal nanoparticles.
AB  - 5-Mercapto-2,2'-bithiophene functionalized metal nanoparticles BTSMs [M: copper
      (Cu), silver (Ag), and gold (Au)] of different diameters (2-8 nm) were
      synthesized. Conductive polymeric metal nanoparticles were formed from BTSM by UV
      irradiation. The photopolymerization mechanism was investigated using transient
      absorption measurements. Intramolecular electron transfer from the ligand to the
      metal nano-core was confirmed. Nanoparticle size, as well as plasmon electronic
      interactions, are important factors. The smaller the nanoparticle and the
      stronger the electronic interactions, the faster the electron transfer is. The
      three-dimensional structure of the polymerized BTSM was identified using
      transmission electron microscopy (TEM) and scanning electron microscopy (SEM).
      The conductivity of polymerized BTSM measured in poly(3,4
      ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) film is higher than
      that of the nonpolymerized BTSM.

PMID- 19862414
TI  - The role of p53 in the efficiency of photodynamic therapy with hypericin and
      subsequent long-term survival of colon cancer cells.
AB  - Photodynamic therapy with hypericin (HY-PDT) is known as an efficient modality
      for treatment of various cancerous and non-cancerous diseases. Although the role
      of p53 protein in cell death signaling is well established, relatively little is
      known of its impact on the efficiency of HY-PDT. Comparison of sensitivity and
      long-term survival of p53-null versus wt-p53-expressing HCT-116 cells is reported
      here. The lack of p53 function did not affect cell proliferation or attenuate the
      initial phases of programmed cell death. However, analyses of apoptosis in the
      final stages revealed suppression of its incidence and delayed activation of
      caspase-3 in p53-null cells. Significantly higher clonogenic ability, especially
      in hypoxia, was identified in the case of p53-null cells. Induction of Mcl-1 and
      Bax levels were more prominent in wt-pt53 cells. Interestingly, the level of Bcl
      2 did not react to HY-PDT at all, in both cell lines. Bringing the evidence
      together, we prove that despite insignificant impact on overall toxicity,
      expression of p53 affects the clonogenic efficiency of HCT-116 cells. Since
      destruction of tumor tissue and its vascular system by PDT tends to lead to
      hypoxia, superior survival of p53-deficient tumor cells under given conditions
      might result in recurrence of cancer diseases.

PMID- 19862416
TI  - Photophysical properties of N-alkylated azahelicene derivatives as DNA
      intercalators: counterion effects.
AB  - In this work, three compounds having the same organic moiety (N-methyl-5
      azahelicenium salts) but different counterions (I-, NO3- and COOCF3-) have been
      investigated in buffered aqueous solutions and in the presence of DNA to give
      information on the counterion effects on the binding. In particular, the
      absorption spectra, fluorescence quantum yields and fluorescence lifetimes in
      aqueous solution for free organic molecules have been determined by steady-state
      and time-resolved spectrofluorimetric measurements. The obtained values are
      compared with those of the chromophores in the presence of increasing
      concentrations of DNA. The results allow determination of the association
      constants (K(a)) and the number of base couples per chromophore molecule (n) by
      means of the McGhee Von Hippel model. The binding parameters are strongly
      affected by the nature of counterions since the highest K(a) value was determined
      for the compound having COOCF3-; on the other hand the NO3- derivative is able to
      interact with the highest number of binding sites. The morphology and structural
      properties of the DNA-chromophore complexes were investigated by circular
      dichroism (CD) and atomic force microscopy (AFM). The data revealed that I- and
      COOCF3- derivatives preferentially form intercalation complexes, while the NO3-
      salt is able to form intercalation and grove binding complexes at the same time.

PMID- 19862417
TI  - Unusually slow proton transfer dynamics of a 3-hydroxychromone dye in protic
      solvents.
AB  - The photophysics of a 3-hydroxychromone dye, 2-(2-furyl)-3-hydroxychromone (FHC)
      was explored in different types of protic solvents by steady-state and time
      resolved fluorescence spectroscopy. FHC exhibits a dual emission, attributable to
      the excited normal (N*) and tautomer (T*) forms resulting from an excited state
      intramolecular proton transfer (ESIPT) reaction (N*-->T*). The ESIPT rate
      decreases with an increase in the hydrogen-bond donating ability of protic
      solvents. The proton-transfer dynamics is found to be unusually slow (
      approximately 10(3) times slower than 3-hydroxyflavone) in strong hydrogen-bond
      donating solvents like methanol, trifluoroethanol or formamide, where it occurs
      on a time scale of approximately 100-260 picoseconds. This slow dynamics is
      likely to be related to the intermolecular solvent-solute H-bonding interactions
      that compete with the intramolecular H-bond in FHC required for the ESIPT
      reaction. These data provide a physical background for recent applications of
      this dye as a fluorescence probe of the microenvironment in biomolecules.

PMID- 19862418
TI  - Photochromic optical memory based on non-destructive IR read-out.
AB  - The photochromic material 1-(2,5-dimethylthien-1,1-dioxide-3-yl)-2-(2,5
      dimethylthien-3-yl)hexafluorocyclopentene (DMTFO2) undergoes reversible
      photocyclization and ring opening reactions upon alternate irradiation with UV
      and visible light, respectively. Upon photocyclization, the closed-ring isomer of
      DMTFO2 showed a strong IR absorption band at 1532 cm(-1) which was not observed
      for the open-ring isomer. To understand the IR spectra of DMTFO2, theoretical
      calculations were carried out using Gaussian 03 program at the B3LYP/6-31G(d)
      level. We also demonstrated non-destructive readout of photochromic recording by
      IR spectral difference between the open- and closed-ring isomers of DMTFO2 in
      film. We found that DMTFO2 exhibited a higher contrast ratio of IR image between
      open- and closed-ring isomer compared with previously reported 1,2-bis(2,5
      dimethylthien-3-yl)perfluorocyclopentene (DMTF6) because of the increased
      photoconversion yield as well as higher vibrational transition intensity. These
      findings along with its high fatigue resistance indicate that DMTFO2 could be an
      excellent candidate for photon-mode RW (re-writable) memory devices based on
      photochromic recording and non-destructive IR read-out.

PMID- 19862419
TI  - Viscosity dependence of rubrene fluorescence quenching by organic radicals via
      energy transfer.
AB  - The kinetics of rubrene (5,6,11,12-tetraphenylnaphthacene) fluorescence quenching
      by energy transfer to the radicals of N,N,N',N'-tetramethyl-para-phenylenediamine
      (TMPD+*), tetracyanoquinonedimethane (TCNQ-*) and galvinoxyl (2,6-di-tert-butyl
      alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-p-tolyloxy; GAL*),
      have been measured in solvents of different viscosities. At room temperature the
      observed quenching rate constants vary between 0.12 and 7.8 x 10(10) M(-1) s(-1),
      always exceeding the diffusion rate constants given by the simplest version of
      Smoluchowski theory combined with the rate constants for dipole-dipole energy
      transfer. This discrepancy is explained by accounting for the non-stationary
      stage in the Forster kinetics, even though the experimental fluorescence decays
      are apparently mono-exponential.

PMID- 19862420
TI  - Temperature influence on deactivation paths and tautomeric equilibrium of some
      photochromic Schiff bases studied by time-resolved and stationary spectroscopy.
AB  - The effect of temperature on spectroscopic properties (stationary and time
      resolved) of selected compounds belonging to the salicylideneaniline and
      hydroquinone families of photochromic Schiff bases is studied. The nonradiative
      decay of the excited keto tautomer consists of two components: the temperature
      independent one (internal conversion, dominant below 200 K) and the temperature
      dependent one (assigned to structural changes). The parameters of these
      components are remarkably different in the two families of the photochromic
      compounds. The influence of the hydrogen bonding ability of the solvent on the
      tautomeric equilibrium between the enol and keto forms indicates changes in the
      order of the ground state energy levels when going from methanol to
      trifluoroethanol.

PMID- 19862421
TI  - Triple proton transfer of excited 7-hydroxyquinoline along a hydrogen-bonded
      water chain in ethers: secondary solvent effect on the reaction rate.
AB  - A large secondary solvent effect on the reaction rate has been experimentally
      observed in the excited-state tautomerization of a 7-hydroxyquinoline (7HQ)
      molecule complexed cyclically with two water molecules in ethers. The proton
      acceptance of a water molecule from the enolic group of 7HQ is the rate
      determining step while the proton donation of a water molecule to the imino group
      of 7HQ is followed rapidly to complete the triple proton transfer of the
      7HQ.(H2O)2 complex in both diethyl ether and di-n-propyl ether. The rate constant
      of the tautomerization is larger in diethyl ether than in di-n-propyl ether due
      to the more polar environment around the complex in diethyl ether. Although the
      activation energies of the proton transfer are similar in both ethers, the
      kinetic isotope effect of the rate constant is larger in di-n-propyl ether than
      in diethyl ether. We attribute these kinetic differences to dissimilarity in the
      polarities of the two secondary solvents.

PMID- 19862422
TI  - Microwave discharge electrodeless lamps (MDEL). Part IV. Novel self-ignition
      system incorporating metallic microwave condensing cones to activate MDELs in
      photochemical reactions.
AB  - A metallic condensing cone that concentrates microwave radiation (equivalent to
      an optical lens) has been developed and used as part of a system to activate a
      microwave discharge electrodeless lamp (MDEL) in the oxidative treatment of
      wastewaters by aiding the novel self-ignition of the lamp on irradiation at low
      microwave power levels. This approach to self-ignition can potentially lead to
      considerable energy savings in such treatments. System performance was examined
      for the ignition power of microwaves of such MDEL devices in water, whose
      usefulness was assessed by investigating the photolytic transformation of aqueous
      solutions of representatives of three classes of contaminants: chlorinated
      phenols, herbicides and endocrine disruptors, specifically 4-chlorophenol (4-CP),
      2,4-dichlorophenoxyacetic acid (2,4-D) and 4,4'-isopropylidenediphenol (bisphenol
      A; BPA), respectively, taken as model wastewaters in air-equilibrated, in oxygen
      saturated and in TiO2-containing aqueous media. The results are discussed in
      terms of the dynamics of the photo-induced degradation processes.

PMID- 19862463
TI  - [BeO-OSL detectors for dose measurements in cell cultures].
AB  - AIM: The absorbed dose is an important parameter in experiments involving
      irradiation of cells in vitro with unsealed radionuclides. Typically, this is
      estimated with a model calculation, although the results thus obtained cannot be
      verified. Generally used real-time measurement methods are not applicable in this
      setting. A new detector material with in vitro suitability is the subject of this
      work. METHODS: Optically-stimulated luminescence (OSL) dosimeters based on
      beryllium oxide (BeO) were used for dose measurement in cell cultures exposed to
      unsealed radionuclides. Their qualitative properties (e. g. energy-dependent
      count rate sensitivity, fading, contamination by radioactive liquids) were
      determined and compared to the results of a Monte Carlo simulation (using AMOS
      software). OSL dosimeters were tested in common cell culture setups with a known
      geometry. RESULTS: Dose reproducibility of the OSL dosimeters was +/-1.5%. Fading
      at room temperature was 0.07% per day. Dose loss (optically-stimulated deletion)
      under ambient lighting conditions was 0.5% per minute. The Monte Carlo simulation
      for the relative sensitivity at different beta energies provided corresponding
      results to those obtained with the OSL dosimeters. Dose profile measurements
      using a 6 well plate and 14 ml PP tube showed that the geometry of the cell
      culture vessel has a marked influence on dose distribution with 188Re.
      CONCLUSION: A new dosimeter system was calibrated with beta-emitters of different
      energy. It turned out as suitable for measuring dose in liquids. The dose profile
      measurements obtained are suitably precise to be used as a check against
      theoretical dose calculations.

PMID- 19862464
TI  - Osteonecrosis of the jaw in patients receiving oral bisphosphonates.

PMID- 19862465
TI  - The heterozygous Lemd3 +/GT mouse is not a murine model for osteopoikilosis in
      humans.
AB  - Osteopoikilosis and the Buschke-Ollendorff syndrome are skeletal dysplasias with
      hyperostotic lesions in the long bones. These disorders are caused by
      heterozygous loss-of-function mutations in the LEMD3 gene. LEMD3 codes for a
      protein of the inner nuclear membrane that, through interaction with R-SMADs,
      antagonizes the BMP and TGF beta 1 pathway. It is suggested that the hyperostotic
      lesions in these disorders are caused by enhanced BMP and TGFbeta1 signaling. The
      exact mechanism by which mutations in the LEMD3 gene lead to these bone lesions
      has not yet been unraveled precisely. To further assess this, an Lemd3 gene
      trapped mouse was created in a gene-trapping program by Baygenomics. To
      investigate whether the heterozygous gene-trapped mouse is a good model for
      osteopoikilosis in humans, we studied these mice radiologically with high
      resolution micro-computed tomography (microCT) and histologically. X-ray images
      were evaluated by a trained radiologist, but no typical osteopoikilosis lesions
      could be recognized. On all microCT reconstructed images a 3D cortical and
      trabecular quantitative analysis was performed, investigating different
      histomorphometric parameters ranging from percent bone volume, bone
      surface/volume ratio over trabecular thickness, separation, number, and pattern
      factor to structure model index and fractal dimension. No significant differences
      were found after a t-test statistical analysis. Also, histological analysis did
      not reveal lesions typical for osteopoikilosis. We conclude that the heterozygous
      Lemd3 gene-trapped mouse is not a good model to study osteopoikilosis and the
      Buschke-Ollendorff syndrome.

PMID- 19862466
TI  - Association between ultrasonographic findings and bone/cartilage biomarkers in
      patients with early-stage knee osteoarthritis.
AB  - Little is known regarding the association between ultrasonographic (US) findings
      and biomarkers of bone and cartilage in individuals with knee osteoarthritis
      (OA). We investigated (1) US findings in early-stage knee OA and (2) the
      association between US findings and bone/cartilage biomarkers. A population
      cohort aged 35-55 years (n = 106) with early-stage knee OA was investigated. US
      examination was performed according to European League against Rheumatism (EULAR)
      guidelines using a 7.5-MHz probe. Biomarkers of bone resorption (CTx-I) and
      formation (PINP), cartilage resorption (U-CTx-II) and synthesis (S-PIIANP), and
      general bone and cartilage biomarkers (OC, COMP) were assessed. The most
      prevalent US findings were tendon calcification, synovial thickening, and
      suprapatellar effusion. In women, the presence of tendon calcification and
      Baker's cysts could predict 36% of the variability in U-CTx-II levels. The
      presence of osteophytes and tendon calcification predicted up to 38% of the
      variability of PIIANP concentration. Defects in subchondral bone, meniscal
      changes, and effusion predicted up to 29% of the variability in COMP levels.
      Tendon calcification was related to cartilage synthesis (based on PIIANP levels)
      in men and to cartilage degradation (based on U-CTx-II concentrations) in women.
      US signs of synovitis were reflected metabolically by markers of joint tissue
      metabolism. Tendon calcification, synovial thickening, and effusion were common
      US findings in early-stage knee OA. US-detectable findings were substantially
      responsible for the variability in bone and cartilage biomarkers, associations
      reflective of the active metabolism of soft tissues in early-stage OA.

PMID- 19862467
TI  - Incidence of osseous interclinoid bars in Indian population.
AB  - PURPOSE: Parasellar interclinoid bars are significant in surgical management
      while dealing with the vascular, neoplastic or traumatic lesions of the central
      skull base and can also compress the surrounding structures giving rise to
      various clinical symptoms. The literature cites several case reports but
      systematic study of these bars has not been done. Therefore this study was
      carried out to see the incidence of osseous interclinoid bars in Indian
      population. METHOD: Two hundred and fifty adult dried human skulls were studied.
      RESULTS: It was observed that the bony bars between the three clinoid processes
      can be divided into four types (Types I, II, III, IV). Due to the presence of
      these bars three types of interclinoid foramina were formed. A total incidence of
      22% of various types of interclinoid bars was observed, out of which 12% were
      Type I, 5.6% Type II, 4% type III and only 0.4% were of type IV variety.

PMID- 19862468
TI  - Alaska, multiple sclerosis, and the vitamin D hypothesis.

PMID- 19862469
TI  - Musty odour, mental retardation, and spastic paraplegia revealing phenylketonuria
      in adulthood.

PMID- 19862470
TI  - Detection of human bocavirus-2 in children with acute gastroenteritis in South
      Korea.
AB  - Human bocavirus (HBoV)-2, a new parvovirus, has been identified in stool samples
      and is suggested to be one of the etiologic agents of acute gastroenteritis (GE).
      The purpose of this study was to investigate the prevalence of HBoV-2 in children
      with GE. Stool samples were collected from 358 children hospitalized with GE.
      HBoV-2 was detected in 3.6% of the patients. HBoV-2 was co-detected with other
      viral agents in 53.8% of the patients. These findings suggest that HBoV-2 may be
      an etiologic agent in GE, but further studies are needed due to frequent co
      detection with other enteric viruses.

PMID- 19862471
TI  - A rapid method for detection of PrP by surface plasmon resonance (SPR).
AB  - Surface plasmon resonance was used to develop a rapid, label-free and sensitive
      immunoassay for detection of Prion protein (PrP). Anti-PrP monoclonal antibodies
      immobilized on the biosensor surface were allowed to bind various concentrations
      of cellular prion protein (PrP(C)), followed by a pulse with additional soluble
      anti-PrP polyclonal antibodies to intensify the signal. The interaction of
      antibody with antigen was monitored in real time. With this method, it was
      possible to detect PrP(C) with a limit of 31.7 ng/ml in serum and 13.1 ng/ml in
      HEPES-saline, requiring 1 h for a single sample measurement. The assay also
      detected misfolded prion protein (PrP(Sc)) in spiked serum and PrP(Sc) in scrapie
      infected mouse brains. This is a rapid and sensitive assay for the detection of
      PrP in serum that could be developed into a platform for a serum-based TSE test.

PMID- 19862472
TI  - An assessment of molecular variability and recombination patterns in South
      African isolates of Potato virus Y.
AB  - The coat protein (CP) gene of 75 South African Potato virus Y (PVY) isolates was
      amplified using reverse-transcriptase polymerase chain reaction (RT-PCR). The
      resulting cDNA products were cloned and sequenced. These sequences were used to
      identify the strains to which the isolates belonged. Some, when compared to
      reference sequences, belonged to the PVY(N) and PVY(O) strains. A number of
      isolates were found to demonstrate significant homology to PVY(N) strains from
      China. A large number of South African isolates possessed CP sequences showing
      evidence of recombination between PVY(N) and PVY(O) strains, similar to those of
      PVY(NTN) isolates. Multiplex RT-PCR analysis allowed further differentiation of
      PVY(O) isolates and revealed that the majority were of the PVY(N)-Wilga strain.
      It was deduced that the most likely way in which these isolates reached South
      Africa was via the importation of infected material.

PMID- 19862474
TI  - Virgaviridae: a new family of rod-shaped plant viruses.
AB  - The new plant virus family Virgaviridae is described. The family is named because
      its members have rod-shaped virions (from the Latin virga = rod), and it includes
      the genera Furovirus, Hordeivirus, Pecluvirus, Pomovirus, Tobamovirus and
      Tobravirus. The chief characteristics of members of the family are presented with
      phylogenetic analyses of selected genes to support the creation of the family.
      Species demarcation criteria within the genera are examined and discussed.

PMID- 19862475
TI  - Late-onset choreoathetotic syndrome following heart surgery.
AB  - Choreoathetotic syndromes are frequently observed in children after congenital
      cardiopathy surgery. To report the case of an adult patient who developed a
      choreoathetotic syndrome after cardiac operation, probably related to a
      transitory hypometabolism of basal ganglia. A 52-year-old patient underwent heart
      surgery under circulatory arrest and deep hypothermia, for type III dissecting
      thoracic aorta aneurysm. Two weeks later she developed an acute choreic syndrome.
      The positron emission tomography using fluorodeoxyglucose (FDGC-PET) showed a
      bilateral hypometabolism of basal ganglia. After haloperidol administration,
      choreic syndrome improved and 6 months later FDGC-PET was normal. Choreoathetosis
      has been described as a rare complication after heart surgery. The authors
      suggest that this movement disorder may be related to hypothermia that can induce
      a reversible basal ganglia metabolic damage.

PMID- 19862477
TI  - The tetracycline resistome.
AB  - Resistance to tetracycline emerged soon after its discovery six decades ago.
      Extensive clinical and non-clinical uses of this class of antibiotic over the
      years have combined to select for a large number of resistant determinants,
      collectively termed the tetracycline resistome. In order to impart resistance,
      microbes use different molecular mechanisms including target protection, active
      efflux, and enzymatic degradation. A deeper understanding of the structure,
      mechanism, and regulation of the genes and proteins associated with tetracycline
      resistance will contribute to the development of tetracycline derivatives that
      overcome resistance. Newer generations of tetracyclines derived from engineering
      of biosynthetic genetic programs, semi-synthesis, and in particular recent
      developments in their chemical synthesis, together with a growing understanding
      of resistance, will serve to retain this class of antibiotic to combat pathogens.

PMID- 19862476
TI  - Subtypes of functional alpha1-adrenoceptor.
AB  - In this review, subtypes of functional alpha1-adrenoceptor are discussed. These
      are cell membrane receptors, belonging to the seven-transmembrane-spanning G
      protein-linked family of receptors, which respond to the physiological agonist
      noradrenaline. alpha1-Adrenoceptors can be divided into alpha1A-, alpha1B- and
      alpha1D-adrenoceptors, all of which mediate contractile responses involving Gq/11
      and inositol phosphate turnover. A fourth alpha1-adrenoceptor, the alpha1L-,
      represents a functional phenotype of the alpha1A-adrenoceptor. alpha1
      Adrenoceptor subtype knock-out mice have refined our knowledge of the functions
      of alpha-adrenoceptor subtypes, particuarly as subtype-selective agonists and
      antagonists are not available for all subtypes. alpha1-Adrenoceptors function as
      stimulatory receptors involved particularly in smooth muscle contraction,
      especially contraction of vascular smooth muscle, both in local vasoconstriction
      and in the control of blood pressure and temperature, and contraction of the
      prostate and bladder neck. Central actions are now being elucidated.

PMID- 19862478
TI  - Chicken type II collagen induced immune balance of main subtype of helper T cells
      in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis.
AB  - OBJECTIVE: To investigate the effect of the oral administration of chicken type
      II collagen (CCII) on T cells from mesenteric lymph node (MLN) lymphocytes in
      rats with collagen-induced arthritis (CIA). METHODS: CIA was induced in male
      Sprague-Dawley rats immunized with CCII in Freund's complete adjuvant. CCII (10,
      20, and 40 microg kg(-1) day(-1), i.g. x 7 days) was administered orally to rats
      from day 14 to 21 after immunization. Arthritis was evaluated by hind paw
      swelling and polyarthritis index, and MLNs and synovium were harvested for
      histological examination. Activity of interleukin-2 (IL-2) in MLN lymphocyte
      supernatant was measured by ConA-induced splenocyte proliferation in C57BL/6J
      mice, and IL-4, IL-17, and transforming growth factor beta (TGF-beta) levels in
      MLN lymphocytes were measured by enzyme-linked immunosorbent assay (ELISA). The
      proportion of CD4(+)CD25(+) Treg cells and Th17 cells was determined by double
      color labeling for flow cytometry analysis. RESULTS: The administration of CCII
      (10, 20, 40 microg/kg, i.g. x 7 days) suppressed secondary inflammatory reactions
      and histological changes in CIA model. The activity of IL-2 and IL-17 produced by
      MLN lymphocytes from CIA rats was significantly inhibited by the administration
      of CCII (10, 20, and 40 microg kg(-1) day(-1)). The levels of IL-4 and TGF-beta
      were increased in CCII (10, 20, and 40 microg kg(-1) day(-1)) groups. The flow
      cytometry analysis showed that CCII (10, 20, and 40 microg kg(-1) day(-1))
      significantly increased the proportion of Treg and decreased the proportion of
      Th17. CONCLUSION: These results indicate that oral administration of CCII had
      therapeutic effects on CIA rats, which was related to decreased production of pro
      inflammatory mediators (IL-2, IL-17) and increased production of anti
      inflammatory mediators (IL-4, TGF-beta). This suggests that CCII plays an
      important role in regulating the immune balance of Th1/Th2 and Th17/Treg in rats
      with CIA.

PMID- 19862479
TI  - Can L(+)-lactate be used as a marker of experimentally induced inflammation in
      rats?
AB  - OBJECTIVE: The purpose of this study was to investigate if L(+)-lactate (lactate)
      can be used as a marker of progression of joint inflammation in comparison with a
      reference marker, prostaglandin E2 (PGE(2)), and to analyse implications for drug
      treatments. MATERIALS AND METHODS: The assessment of the inflammation time course
      and the treatment efficacy studies were performed on two occasions. At specific
      time points, synovial fluid was extracted from Sprague-Dawley rats (n = 87)
      challenged with either carrageenan (Cg) or Freund's complete adjuvant (FCA) or
      from six non-inflamed rats. Naproxen (7.5 or 30 micromol/kg) or rofecoxib (30
      micromol/kg) was administered per os 2 h post Cg or at 48 h post FCA. Levels of
      PGE(2) and lactate were assessed either by immuno-assay or by colorimetric assay.
      RESULTS: Increased levels of both markers were detected following Cg or FCA
      injection. Pharmacological treatments resulted in lower concentrations of PGE(2)
      whereas levels of lactate remained unaffected compared to the vehicle-treated
      group. CONCLUSION: Our results suggest that lactate may be useful as an
      additional biomarker of inflammatory processes, especially for monitoring the non
      cox-inhibitor sensitive cascade.

PMID- 19862481
TI  - Intense accumulation of 18F-FDG, not enhancement on MRI, helps to guide the
      surgical biopsy accurately in soft tissue tumors.
AB  - Soft tissue sarcomas are a highly heterogeneous group of malignancies that arise
      from mesenchymal tissues. Grading of soft tissue sarcomas is an important
      prerequisite for the choice of therapy and estimation of prognosis. However,
      incisional biopsy of huge soft tissue sarcoma lesions frequently fails to provide
      an accurate diagnosis when there is a benign component, cystic changes and/or
      necrosis. MRI is helpful in evaluating the extent of the sarcoma lesion,
      vascularization, invasiveness and integrity of surrounding tissue, but definitive
      differentiation of benignity and malignancy is not possible with it. In this
      study, positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose
      successfully guided surgeons to identify the most hypermetabolic and, therefore,
      the most suitable biopsy sites of huge soft tissue sarcoma.

PMID- 19862480
TI  - Entamoeba histolytica and E. dispar infections in captive macaques (Macaca
      fascicularis) in the Philippines.
AB  - Entamoeba histolytica is a protozoan parasite that infects man and animals. This
      parasite has a global distribution and the disease it causes is usually
      characterized by diarrhea. In order to detect the parasite, it is necessary to
      differentiate it from Entamoeba dispar. E. dispar appears morphologically similar
      to E. histolytica but does not cause disease and tissue invasion. This study
      reports on the prevalence of E. histolytica and E. dispar among captive macaques
      in a primate facility in the Philippines. PCR was used to correctly identify both
      Entamoeba species. Indirect fluorescent antibody test (IFAT) was also performed
      to determine the seroprevalence of amebiasis in the captive macaques. Based on
      PCR targeting of the peroxiredoxin gene, of the 96 stool samples collected, 23
      (24%) contained E. histolytica while 32 (33%) contained E. dispar. IFAT revealed
      26 (27%) serum samples positive for antibodies against E. histolytica. Sequence
      analysis of the 18S rRNA gene showed that the 23 E. histolytica isolates were
      identical to human E. histolytica isolates deposited in the GenBank and not
      Entamoeba nuttalli as found in macaques in other recent reports. The Philippines
      is a major exporter of monkeys for biomedical research purposes, so screening
      animals before transporting them to other locations lessens the risk of spreading
      zoonoses to a wider area. This is the first report of the molecular detection of
      E. histolytica and E. dispar among macaques in the Philippines. This study
      complements the limited information available on the animal hosts of E.
      histolytica in the Philippines.

PMID- 19862482
TI  - Bibliometric study of radiation application on microdose useful for new drug
      development.
AB  - In spite of the sharp increase in both private and government R&D fund, the
      number of newly approved medicines for market had decreased since the 1990s. This
      is attributed to a large extent to the bottleneck in the critical path arising
      from the great disparity between animal model in pre-clinical trial and human
      model in clinical trial. This bottleneck may be expected to be gotten rid of by
      change in paradigm of drug development based on microdosing, which is enabled by
      radiation-related imaging technology. However, this is impossible without being
      accompanied by interdisciplinary joint researches, in which clinical
      investigators belonging to medical schools or hospitals play the most decisive
      role. In this article, authors verify based on bibliometrics that Japan has not
      employed the opportunity for revitalizing drug research activities because
      Japanese researchers' attitude toward radiation technology may not be so positive
      in comparison with the US, and because the role which clinical investigators play
      in the phase of pre-clinical trial is smaller in Japan than in the US.

PMID- 19862485
TI  - [Improving medication safety].
AB  - Drug treatment is beneficial in most patients but can also cause adverse events
      and death. Since preventable adverse drug events are a relevant cause of
      morbidity and mortality, strategies for improving medication safety are
      warranted. Studies demonstrate that system failure is the most relevant cause of
      preventable adverse drug events, with prescribing errors being the most relevant.
      Lack of information either about the patient, the functioning of a patient's
      organs and concurrent medications, or about the prescribed drug, its correct
      dosing, contraindications and drug interactions often lead to preventable adverse
      drug events. International studies show that medication errors result in more
      people dying than from traffic accidents. Therefore, in addition to the safety of
      the drug, it is necessary that the safety of the process of drug treatment must
      be taken care of. This is called medicine safety. In order to improve medicine
      safety, it is necessary to consider the organization of the medication process,
      instead of looking for an individual to blame. The goal of the "Action Plan for
      Medication Safety in Germany" ("Aktionsplan Arzneimitteltherapiesicherheit fur
      Deutschland") from the Federal Ministry of Health is to optimize patient safety
      in drug treatment by the joint efforts of physicians, pharmacists, patients, and
      politicians.

PMID- 19862483
TI  - MK886-induced apoptosis depends on the 5-LO expression level in human malignant
      glioma cells.
AB  - Mounting evidence suggests that lipoxygenase (LO)-catalyzed products may play a
      key role in the development and progression of human cancers. In this study, we
      analyzed the effects of a 5-LO inhibitor, which inhibits the conversion of
      arachidonic acid to leukotrienes, on cell proliferation and apoptosis in human
      malignant glioma cells, including 5-LO-expressing cells U-87MG, A172 and 5-LO non
      expressing cell U373. Growth of U-87MG and A172 cells, but not that of U373
      cells, was inhibited in a dose-dependent manner by treatment with MK886.
      Similarly, specific 5-LO silencing by small interfering RNA reduced the growth of
      U-87MG and A172 cells. MK886 treatment reduced 5-LO activity independently of 5
      LO-activating protein (FLAP) in human malignant glioma cells. MK886 treatment
      also induced cell apoptosis, measured by DNA fragmentation and nuclear
      condensation, in U-87MG and A172 cells but there were no signs in U373 cells.
      Moreover, this treatment reduced ERKs phosphorylation and anti-apoptotic molecule
      Bcl-2 expression, and increased Bax expression in U-87MG and A172 cells. In
      summary, our results show there is a link between the 5-LO expression status and
      the extent of MK886-inhibited cell proliferation and apoptosis. Taken together,
      this study suggest that 5-LO is a possible target for treating patients with
      gliomas, and 5-LO inhibition might be potent therapy for patients with 5-LO
      expressing malignant gliomas.

PMID- 19862486
TI  - [Threshold values, guiding values, benchmarks, action values: definitions and
      determination with examples from the UBA].

PMID- 19862484
TI  - A separation defect of tapetum cells and microspore mother cells results in male
      sterility in Brassica napus: the role of abscisic acid in early anther
      development.
AB  - Male sterility is an important contributor to heterosis in Brassica napus L. The
      B. napus line 7-7365ABC is a recessive epistatic genic male sterile (REGMS) three
      line system. The 7-7365A line with the genotype Bnms3ms3ms4ms4RfRf is male
      sterile, while the 7-7365B line with the genotype BnMs3ms3ms4ms4RfRf is male
      fertile, and 7-7365C with homozygous recessive genotypes at the three loci shows
      male fertility because the loss function of Bnrf gene causes the inhibition of
      the genetic trait of the double mutant Bnms3 Bnms4. Histological studies
      addressing male sterility, transcriptional regulation pathways and the role of
      abscisic acid (ABA) in the anther development of REGMS plants are reported here.
      In the male-sterile line 7-7365A, tapetum cell and microspore mother cell
      separation were affected, and this led to failure of microspore release. The
      activity of polygalacturonase and the expression of the pectin methylesterase
      gene (AT3g06830) were significantly downregulated. Nine genes were downregulated
      in 7-7365A compared to 7-7365B and 7-7365C, including genes specifically
      expressed in tapetum (A3, A9, MS1) and the ABA-responsive gene KIN1. ABA
      concentration in 7-7365B was significantly higher than in 7-7365A and 7-7365C in
      young flower buds. Furthermore, temperature treatment made some sterile 7-7365A
      flowers become fertile. The stamens in these flowers produced viable pollen, and
      filament elongation was restored to its level in 7-7365C. We propose that ABA
      might control the expression of genes involved in cell separation during early
      anther development. The REGMS phenotype could be controlled by a primary pathway
      of male sterile metabolism positively regulated by the BnMs3 gene and a
      supplementary pathway negatively regulated by the BnRf gene.

PMID- 19862487
TI  - [Perception of health risks: psychological and social factors].
AB  - This article reviews central findings and current developments of psychological
      and sociological research on the perception of health risks. Risk perception is
      influenced by numerous psychological, social, political, and cultural factors.
      These factors can be categorized into (a) risk characteristics, (b)
      characteristics of the risk perceiving person and his/her situation, and (c)
      characteristics of risk communication. Thus, besides individual cognitive and
      affective processing of risk information, social processes of risk amplification
      (e.g., media effects) are also involved in the construction of individual risk
      perceptions. We discuss the recommendations for health risk communication that
      follow from these findings with regard to different communication goals.

PMID- 19862488
TI  - [Risk perception and psychological reactions in public crisis situations using
      the example of terror attacks].
AB  - The reactions to the 9/11 terror attacks were immense in the western population.
      In the current review, the impact of terror attacks is presented with surveys,
      clinical interviews, and scientific polls, which were identified in a
      comprehensive literature search. Results show that the fear of further terror
      attacks is comparatively overestimated in the population and is associated with
      numerous psychological consequences and reactions. The overestimation of the
      probability of further terror attacks is related among other reasons to its
      unique features and its strong representation in the media. Several independent
      studies proved that the number of stress symptoms and psychiatric diagnoses is
      associated with a high risk perception in relation to terror attacks. This was
      not only the case for victims of terror attacks, but also for people indirectly
      exposed to the terror attacks. In addition, there is evidence that the number of
      the stress symptoms correlate with the duration of TV consumption of new findings
      about terror attempts. Methodologically, there is a critical lack of more in
      depth analyses to explain the development of risk perceptions and its influence
      on mental and physical health. Because of the international importance and cross
      cultural differences, an international standardization of research is desirable.

PMID- 19862489
TI  - [HPV infections of the oral and genital mucosa. Possibilities for primary
      prevention].
AB  - It is well accepted today that almost all cases of carcinoma of the cervix are
      caused by persistent infections with high-risk human papilloma viruses (HPV),
      especially through types HPV16 and HPV18 (ca. 70%). These same types are also
      responsible for some carcinomas of the vulva, anus, penis and oropharynx. This
      knowledge indicates that it should be possible to prevent these carcinomas if a
      majority of the causstive HPV infections can be prevented.

PMID- 19862490
TI  - Ambulatory hernia surgery under local anesthesia is feasible and safe in obese
      patients.
AB  - Ambulatory hernia surgery under local anesthesia is becoming more widely used
      worldwide. Although many reports include obese patients, there are no studies
      that report specifically on the feasibility and safety of ambulatory hernia
      surgery in this category of patients. This paper documents our experience in this
      respect. The present investigation is an observational study performed at the CRS
      Hernia Center, Santiago, Chile, on 510 obese and 1,521 non-obese patients with
      all kinds of hernias susceptible to ambulatory hernia repair under local
      anesthesia. Both tissue and mesh repairs were performed. Obesity was defined as a
      body mass index (BMI) greater than 30. Patients with a BMI greater than 45 were
      excluded from this study. Operative time and pain experienced during the
      intervention were recorded. During the controls performed by a staff member at
      the 7th postoperative day, a questionnaire was answered by each patient regarding
      satisfaction, complaints, and postoperative pain. A second questionnaire was
      completed on the 30th postoperative day. Satisfaction and pain were both measured
      by means of a 10-point visual analog scale (VAS). The mean age was similar in
      both groups (51 years for non-obese and 52 years for obese patients). Obesity was
      present in 38.3% of women and in 17.5% of men (P < 0.002). Diabetes and
      hypertension were observed in a significantly (P < 0.004 and P < 0.02,
      respectively) higher proportion of obese patients. The duration of the operation
      on obese patients was 78 min compared with 62 min in non-obese patients (P <
      0.001). Pain experienced during the intervention was significantly higher in
      obese patients with a VAS of 2.4 vs. in lean patients with a VAS of 2.0 (P <
      0.01). At 24 h, pain was significantly higher and satisfaction significantly
      lower in obese patients (P < 0.007 and P < 0.0001, respectively). All other
      parameters were similar in both groups. At 30 days, infection was present in 0.7%
      of lean patients and in 2.1% of obese patients (P < 0.02). The frequency of
      hematomas, funicular swelling, and pain was similar in both groups. We conclude
      that ambulatory abdominal wall hernia repair under local anesthesia is feasible
      in obese patients. Because of the increased length of surgery in these patients,
      monitored sedation and prophylactic antibiotic cover should be used. The slight
      decrease in patient satisfaction is balanced by the lower risks and higher costs
      associated with full general anesthetic.

PMID- 19862491
TI  - Monoglyceride and diglyceride production through lipase-catalyzed glycerolysis
      and molecular distillation.
AB  - Distilled glycerides are obtained through distillation of the system mono
      diglycerides which is produced from the esterification reaction between a
      triglyceride with glycerol. In this work, monoglycerides (MG) and diglycerides
      (DG) are produced through lipase-catalyzed glycerolysis of soybean oil using
      Candida antarctica B in a solvent-free system. To separate the products of the
      reaction in order to obtain essentially MG and an oil of DG, it is necessary to
      use a suitable process in order to preserve the stability of the components and
      to keep the products free of inappropriate solvents. So, after 24 h of enzymatic
      reaction, the mixture of acylglycerols and fatty acids was distilled into a
      centrifugal molecular distiller, since it provides a free solvent and lower
      temperature environment to increase the desired product concentration. Starting
      from a material with 25.06% of triglycerides (TG), 46.63% of DG, 21.72% of MG,
      5.38% of free fatty acids (FFA), and 1.21% of glycerol, the MG purity in the
      distillate stream was 80% at evaporator temperature (T (E)) equal to 250 degrees
      C and feed flow rate (Q) equal to 10.0 mL/min. At these conditions, the MG
      recovery was 35%. The material collected in the residue stream presented DG
      enriched oil with TG unhydrolyzed, residual MG, and low acidity (29.83% of TG,
      53.20% of DG, 15.64% of MG, and 1.33% of FFA), which is suitable to replace TG
      oil in the human diet.

PMID- 19862492
TI  - Neurotensin and neuromedin N are differentially processed from a common precursor
      by prohormone convertases in tissues and cell lines.
AB  - Neurotensin (NT) is synthesized as part of a larger precursor that also contains
      neuromedin N (NN), a six amino acid NT-like peptide. NT and NN are located in the
      C-terminal region of the precursor (pro-NT/NN) where they are flanked and
      separated by three Lys-Arg sequences. A fourth dibasic sequence is present in the
      middle of the precursor. Dibasics are the consensus sites recognized and cleaved
      by specialized endoproteases that belong to the family of proprotein convertases
      (PCs). In tissues that express pro-NT/NN, the three C-terminal Lys-Arg sites are
      differentially processed, whereas the middle dibasic is poorly cleaved.
      Processing gives rise mainly to NT and NN in the brain, NT and a large peptide
      with a C-terminal NN moiety (large NN) in the gut, and NT, large NN, and a large
      peptide with a C-terminal NT moiety (large NT) in the adrenals. Recent evidence
      indicates that PC1, PC2, and PC5-A are the prohormone convertases responsible for
      the processing patterns observed in the gut, brain, and adrenals, respectively.
      As NT, NN, large NT, and large NN are all endowed with biological activity, the
      evidence reviewed here supports the idea that posttranslational processing of pro
      NT/NN in tissues may generate biological diversity of pathophysiological
      relevance.

PMID- 19862493
TI  - [First clinical experience with a moderately bent laryngoscope for endolaryngeal
      surgery].
AB  - INTRODUCTION: In this article we describe the successful use of a moderately bent
      laryngoscope in two different patient cases. MATERIALS: We developed a prototype
      of a 20 degrees bent laryngoscope. The moderate curvature allows insertion of the
      laryngoscope without using any optical device. The operation is performed via a
      laterally attached 30 degrees nasal endoscope and a monitor, with slightly bent
      instruments. Previous work by our group showed that when a bent laryngoscope was
      used, the forces on the oropharyngeal tissues were significantly reduced.
      Furthermore, the use of these laryngoscopes significantly improves the exposure
      of the endolarynx. RESULTS: We present two cases in which insertion of a
      conventional straight laryngoscope was not possible due to anatomical reasons.
      However, the operations could be performed successfully with the bent
      laryngoscope.

PMID- 19862494
TI  - [Psychosomatic treatment of otorhinolaryngological diseases].
AB  - The spectrum of psychosomatic diseases in the field of otorhinolaryngology covers
      reactive disorders brought on by excessive psychosocial demands, post-traumatic
      disorders following mental traumatization, purely psychological disorders brought
      on by personality development deficits or learnt false behavior, and
      multifactorial diseases with somatic correlatives and mental triggers.
      Psychosomatic medicine describes the interaction of physical and psychological
      processes. The central treatment method is psychotherapy. In Germany, the costs
      of psychodynamic psychotherapies and behavioral therapy are covered by the health
      insurance companies. The tasks of psychosomatic treatment in the field of
      otorhinolaryngology comprise differential diagnostics, basic psychosomatic
      treatment and the determination of differential indications for the respective
      forms of psychotherapy.

PMID- 19862495
TI  - [Functional and subjective results following subtalar dislocations].
AB  - BACKGROUND: The objective of our study is to evaluate the functional and
      subjective results following subtalar dislocations without any associated bone
      injuries and to examine whether the direction of dislocation has any effect on
      the post-traumatic results. METHODS: Over the period from February 1998 to May
      2006, 56 patients with a subtalar dislocation were enrolled in the study. A
      subtalar dislocation without any associated bone injuries was only present in 13
      patients. Follow-up examination after an average of 39.8 months was performed
      using the AOFAS Ankle-Hindfoot scale. The adapted classification developed by
      Altman was used to assess the post-traumatic degree of arthrosis radiologically.
      RESULTS: The average AOFAS score was 81, with good results in 11 patients and
      satisfactory results in 2 patients. The range of motion (ROM) for the ankle
      hindfoot joint was 39.2 degrees . CONCLUSION: Despite the severity of the injury,
      the functional and subjective results of subtalar dislocations without any bone
      injuries are good. Generally, no early post-traumatic arthrosis occurs if there
      are no associated bone injuries. No differences were established between medial
      and lateral subtalar dislocations.

PMID- 19862496
TI  - [Variability of the screw position after 3D-navigated sacroiliac screw fixation.
      Influence of the surgeon's experience with the navigation technique].
AB  - BACKGROUND: The precision of sacroiliac screw placement can be improved with the
      use of navigation techniques. The purpose of this study was to evaluate the
      accuracy of 3D-navigated sacroiliac screw positioning in relation to the
      surgeon's experience with the navigation technique. PATIENTS AND METHODS: A
      consecutive series of 3D-navigated sacroiliac screw placements were prospectively
      evaluated between December 2005 and February 2008. Postoperatively the precision
      of screw placement was analyzed in relation to the surgeon's navigation
      experience with a CT-scan using the criteria of Smith. RESULTS: A total of 37
      screws were implanted by 7 surgeons in 33 patients. In the group of surgeons with
      less experience in navigation techniques two cases of malpositioning led to
      revision of the screws. No screws which were implanted or assisted by surgeons
      experienced in navigation needed to be revised. There was no significant
      difference in the malposition rate. CONCLUSION: In the clinical setup a
      malpositioning of sacroiliac screws is possible even with the use of 3D
      navigation. One reason may be a low level of navigation experience of the surgeon
      in combination with low experience in the conventional technique. Therefore even
      in navigation-based placement of sacroiliac screws the malpositioning rate is
      dependent on the surgeon's experience with the navigation technique. The correct
      placement of the screws should be controlled intraoperatively using the 3D image
      intensifier.

PMID- 19862497
TI  - Clustering, haplotype diversity and locations of MIC-3: a unique root-specific
      defense-related gene family in Upland cotton (Gossypium hirsutum L.).
AB  - MIC-3 is a recently identified gene family shown to exhibit increased root
      specific expression following nematode infection of cotton plants that are
      resistant to root-knot nematode. Here, we cloned and sequenced MIC-3 genes from
      selected diploid and tetraploid cotton species to reveal sequence differences at
      the molecular level and identify chromosomal locations of MIC-3 genes in
      Gossypium species. Detailed sequence analysis and phylogenetic clustering of MIC
      3 genes indicated the presence of multiple MIC-3 gene members in Gossypium
      species. Haplotypes of a MIC-3 gene family member were discovered by comparative
      analysis among consensus sequences across genotypes within an individual clade in
      the phylogram to overcome the problem of duplicated loci in the tetraploid
      cotton. Deficiency tests of the SNPs delimited six A(t)-genome members of the MIC
      3 family clustered to chromosome arm 4sh, and one D(t)-genome member to
      chromosome 19. Clustering was confirmed by long-PCR amplification of the
      intergenic regions using A(t)-genome-specific MIC-3 primer pairs. The clustered
      distribution may have been favored by selection for responsiveness to evolving
      disease and/or pest pressures, because large variants of the MIC-3 gene family
      may have been recovered from small physical areas by recombination. This could
      give a buffer against selection pressure from a broad range of pest and pathogens
      in the future. To our knowledge, these are the first results on the evolution of
      clustering and genome-specific haplotype members of a unique cotton gene family
      associated with resistant response against a major pathogen.

PMID- 19862498
TI  - The economic costs of diabetes in developing countries: some concerns and
      recommendations.

PMID- 19862499
TI  - The endothelin receptor antagonist avosentan ameliorates nephropathy and
      atherosclerosis in diabetic apolipoprotein E knockout mice.
AB  - AIMS/HYPOTHESIS: There is convincing evidence that the endothelin system
      contributes to diabetic nephropathy and cardiovascular disease. This study aimed
      to assess the effects of the non-peptidergic endothelin receptor A (ETA)
      antagonist avosentan in a mouse model of accelerated diabetic nephropathy and
      atherosclerosis in comparison with the ACE inhibitor, quinapril. METHODS:
      Apolipoprotein E (Apoe) knockout (KO) mice (n = 20 per group, five groups) were
      randomised to the following groups: non-diabetic controls and streptozotocin
      induced diabetic animals gavaged daily for 20 weeks with placebo, avosentan (high
      dose: 30 mg/kg, or low dose: 10 mg/kg) or quinapril (given in drinking water, 30
      mg/kg). RESULTS: BP was unchanged by avosentan treatment but decreased with
      quinapril treatment. Diabetes-associated albuminuria was significantly attenuated
      by high-dose avosentan after 10 and 20 weeks of treatment. Diabetic animals
      showed a decreased creatinine clearance, which was normalised by avosentan
      treatment. In diabetic mice, high-dose avosentan treatment significantly
      attenuated the glomerulosclerosis index, mesangial matrix accumulation,
      glomerular accumulation of the matrix proteins collagen IV, and renal expression
      of genes encoding connective tissue growth factor, vascular endothelial growth
      factor, transforming growth factor beta and nuclear factor kappaB (p65 subunit).
      Furthermore, high-dose avosentan treatment was also associated with reduced
      expression of the genes for ETA, ETB and angiotensin receptor 1. The
      renoprotective effects of avosentan were comparable or superior to those observed
      with quinapril. High-dose avosentan also significantly attenuated diabetes
      associated aortic atherosclerosis in Apoe KO mice and reduced macrophage
      infiltration and aortic nitrotyrosine expression. CONCLUSIONS/INTERPRETATION:
      This study demonstrates that ETA blockade with avosentan may provide an alternate
      therapeutic strategy for the treatment of diabetic micro- and macrovascular
      complications.

PMID- 19862500
TI  - ACL graft migration under cyclic loading.
AB  - Elongation and migration of ACL grafts will lead to a deterioration of the
      initial stability of ACL reconstructions. The graft migration has been sparsely
      investigated independently from the elongation of the graft-fixation complex. The
      hypothesis of this investigation was that cyclic tensile loads cause a measurable
      migration of the grafts. Three graft/fixation combinations were investigated in
      human femora (n = 7): human bone-patellar tendon grafts fixed with a
      biointerference screw (BPTG-IS) and free tendon grafts (porcine) fixed with
      either a Bio-TransFix pin (FTG-TF) or an Endobutton CL (FTG-EB). The grafts were
      fitted with tantalum markers. Then, the specimens were repetitively loaded (50
      250 N, 800 cycles). The marker position was fluoroscopically determined at
      defined intervals and the migration calculated from the change in position
      relative to a fiducial marker within the bone. A migration of the grafts occurred
      in all three groups. The migration in the FTG-EB group was significantly larger
      than in the two other groups (P < 0.01). After 800 cycles, average migration was
      0.3 (+/-0.2) mm in the BPTG-IS group, 0.7 (+/-0.4) mm FTG-TF group, 2.0 (+/-1.3)
      mm in the FTG-EB group. This migration might contribute to a loss of initial
      stability. Because the graft migration was dependent on the technique, the
      presented data might provide additional arguments for making the decision on the
      most appropriate graft/fixation combination.

PMID- 19862502
TI  - Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by
      use of a functional assay, the functional analysis of separated alleles in yeast,
      in human lung cells.
AB  - Recent concern has centred on the effects of continuous exposure to low
      concentrations of benzene, both occupationally and environmentally. Although
      benzene has for a long time been recognised as a carcinogen for humans, its
      mechanistic pathway remains unclear. Since mutations in the tumour suppressor
      gene TP53 are the most common genetic alterations involved in human cancer, our
      objective was to establish the first mutational pattern induced by benzene on the
      TP53 gene in human type II-like alveolar epithelial A549 cells by using the
      Functional Analysis of Separated Alleles in Yeast (FASAY). Seventeen mutations
      linked to benzene exposure were found: 3 one- or two-base deletions, and 14
      single nucleotide substitutions (1 nonsense and 13 missense mutations). A>G and
      G>A transitions were the most prevalent (23.5% for both). Other mutations
      included A>C transversions and deletions (3/17, 17.6% for both), G>T
      transversions (2/17, 11.8%) and A>T transversions (1/17, 5.9%). Data arising from
      this benzene-induced mutational pattern affecting TP53, a critical target gene in
      human carcinogenesis, have been compared with those reported in human acute
      myeloid leukaemia, the aetiology of which is clearly linked to benzene exposure,
      and in experimental benzene-induced carcinoma. This comparison suggests that A>G
      transition could be a fingerprint of benzene exposure in tumours. Furthermore,
      our results demonstrate that FASAY is a promising tool for the study of the
      carcinogenic potency of benzene in the human lung.

PMID- 19862501
TI  - Cypermethrin exposure during puberty disrupts testosterone synthesis via
      downregulating StAR in mouse testes.
AB  - Cypermethrin is a widely used synthetic pyrethroid insecticide. Previous studies
      showed that cypermethrin significantly decreased the fertility and reduced the
      number of implantation sites and viable fetuses in females impregnated by males
      exposed to cypermethrin. As yet, little is known about the mechanism of
      cypermethrin-induced reproductive toxicity. In the present study, we investigated
      the effects of cypermethrin exposure during puberty on steroidogenesis in mice.
      Young male mice were administered with cypermethrin (25 mg/kg) by gavage daily
      from postnatal day (PND) 35 to PND70. Results showed that the level of serum and
      testicular testosterone (T) was markedly decreased in cypermethrin-treated mice.
      Additional experiment showed that cypermethrin exposure during puberty markedly
      downregulated mRNA level of steroidogenic acute regulatory protein (StAR) in
      testes. Correspondingly, protein level of testicular StAR was significantly
      decreased in cypermethrin-treated mice. Cypermethrin exposure during puberty did
      not affect the number of Leydig cells in testes. Although cypermethrin exposure
      during puberty did not affect the weight of testes and epididymides, the number
      of sperm in the cauda epididymides was significantly decreased in cypermethrin
      treated mice. Taken together, these results indicate that cypermethrin exposure
      during puberty significantly disrupts T synthesis via downregulating the
      expression of testicular StAR. The decreased T synthesis might be associated with
      cypermethrin-induced impairment in spermatogenesis in mice.

PMID- 19862503
TI  - Effect of prenatal and perinatal acrylamide on the biochemical and morphological
      changes in liver of developing albino rat.
AB  - Acrylamide has been employed as an experimental probe to investigate biochemical
      and morphological changes in developing rat liver following toxin administration
      in pregnant rats. Non-anesthetized pregnant rats were given acrylamide by gastric
      intubation at a dose of 10 mg/kg/day. The pups were divided into three groups:
      Group A, mothers were treated with saline (control group); Group B, mothers were
      treated with acrylamide from day D7 of gestation till birth (prenatal
      intoxication); Group C, mothers were treated with acrylamide from D7 of gestation
      to D28 after birth (perinatal intoxication). Acrylamide-induced biochemical
      changes (in liver and serum) and morphological changes (in liver) were studied in
      control and acrylamide-treated developing pups. Prenatally and perinatally
      administered acrylamide significantly increased lipid peroxidation and reduced
      glutathione and total thiol levels in liver. Significant inhibition of peroxidase
      and superoxide dismutase activities was observed in liver tissue. Total lipids
      including cholesterol and triglycerides were significantly increased in the
      serum. Acrylamide treatment increased serum alanine aminotransferase and
      aspartate aminotransferase activities and inhibited alkaline phosphatase
      activity. Sodium and potassium concentrations were increased, but calcium,
      phosphorus and iron levels were significantly reduced in the serum. Acrylamide
      produced significant electrophoretic changes in serum proteins. The most
      noticeable change was splitting of beta-globulin into beta1- and beta2-globulins.
      Light microscopy showed acrylamide-induced fatty deposits, congested central
      vein, vacuolization and chromatolysis in hepatocytes. Ultrastructural studies
      revealed vacuolated cytoplasm, lipid droplets of variable size and mitochondria
      with damaged cristae and vacuolization. The nuclei in acrylamide-treated groups
      showed marked decrease in the staining of nuclear DNA.

PMID- 19862504
TI  - Biomarkers of organophosphorus nerve agent exposure: comparison of phosphylated
      butyrylcholinesterase and phosphylated albumin after oxime therapy.
AB  - Organophosphorus nerve agents inhibit the activity of cholinesterases by
      phosphylation of the active site serine. In addition, sarin, cyclosarin, soman
      and tabun have been shown to phosphylate a tyrosine residue in albumin. Therapies
      against nerve agent poisoning include the use of oximes to reactivate inhibited
      cholinesterases by displacement of the phosphyl moiety and hence detectable
      levels of adducts with cholinesterases may be reduced. Adducts with tyrosine have
      been shown to be persistent in the guinea pig in the presence of oxime therapy.
      Plasma samples obtained from an animal study aimed at improving therapy against
      nerve agent poisoning were used to compare the suitability of tyrosine and
      butyrylcholinesterase (BuChE) adducts as biomarkers of nerve agent exposure after
      treatment with therapeutic oximes. Under the terms of the project licence, these
      samples could be collected only on death of the animal, which occurred within
      hours of exposure or when culled at 23 or 24 days. Tyrosine adducts were detected
      in all samples collected following intra-muscular administration of twice the
      LD50 dose of the respective nerve agent. Aged BuChE adducts were detected in
      samples collected within a few hours after administration of soman and tabun, but
      not after 23 or 24 days. No BuChE adducts were detected in animals exposed to
      sarin and cyclosarin where samples were collected only after 23 or 24 days.

PMID- 19862505
TI  - The challenge of analyzing beta-blocker drugs in sludge and wastewater.
AB  - In this study, different approaches were used to assess and overcome the severe
      effects of interference from the sample matrix from different types of sludges
      and wastewater on the analysis of nine beta-blockers and the beta sympathomimetic
      clenbuterol. The partitioning of the target compounds into sludge was
      investigated in wastewater treatment plants (WWTPs) in both Canada and Germany to
      evaluate whether this is an important mechanism for removal from sewage. Due to
      ion suppression in the electro spray interface, absolute recoveries were for
      certain compounds even lower than 20%. By using surrogate standards, acceptable
      relative recoveries of >75% were achieved for WWTP influents and effluents and
      for sludges. These matrix effects underline the need to use appropriate surrogate
      standards to aid in analyte quantitation. Using the developed methods, beta
      blockers were detected at concentrations up to 2 microg/L in WWTP effluents, with
      metoprolol, sotalol, and atenolol present as the dominant compounds. Removal
      rates within WWTPs were highly inconsistent and ranged from 1-69%. Propranolol
      showed the greatest degree of partitioning into sludge with solid/water partition
      coefficients of one order of magnitude higher than those for all other compounds.
      However, even for propranolol, sorption did not contribute significantly to the
      overall elimination in WWTPs. It is likely that the removal of beta-blockers
      during waste water treatment can be attributed primarily to microbial
      biodegradation.

PMID- 19862506
TI  - Determination of perfluorinated alkyl acid concentrations in human serum and milk
      standard reference materials.
AB  - Standard Reference Materials (SRMs) are certified reference materials produced by
      the National Institute of Standards and Technology that are homogeneous materials
      well characterized with values for specified properties, such as environmental
      contaminant concentrations. They can be used to validate measurement methods and
      are critical in improving data quality. Disagreements in perfluorinated alkyl
      acid (PFAA) concentrations measured in environmental matrices during past
      interlaboratory comparisons emphasized the need for SRMs with values assigned for
      PFAAs. We performed a new interlaboratory comparison among six laboratories and
      provided, for the first time, value assignment of PFAAs in SRMs. Concentrations
      for perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and other PFAAs
      in two human serum and two human milk SRMs are reported. PFAA concentration
      measurements agreed for serum SRM 1957 using different analytical methods in six
      laboratories and for milk SRM 1954 in three laboratories. The interlaboratory
      relative standard deviation for PFOS in SRM 1957 was 7%, which is an improvement
      over past interlaboratory studies. Matrix interferences are discussed, as well as
      temporal trends and the percentage of branched vs. linear isomers. The
      concentrations in these SRMs are similar to the present-day average
      concentrations measured in human serum and milk, resulting in representative and
      useful control materials for PFAA human monitoring studies.

PMID- 19862507
TI  - See what you eat--broad GMO screening with microarrays.
AB  - Despite the controversy of whether genetically modified organisms (GMOs) are
      beneficial or harmful for humans, animals, and/or ecosystems, the number of
      cultivated GMOs is increasing every year. Many countries and federations have
      implemented safety and surveillance systems for GMOs. Potent testing technologies
      need to be developed and implemented to monitor the increasing number of GMOs.
      First, these GMO tests need to be comprehensive, i.e., should detect all, or at
      least the most important, GMOs on the market. This type of GMO screening requires
      a high degree of parallel tests or multiplexing. To date, DNA microarrays have
      the highest number of multiplexing capabilities when nucleic acids are analyzed.
      This trend article focuses on the evolution of DNA microarrays for GMO testing.
      Over the last 7 years, combinations of multiplex PCR detection and microarray
      detection have been developed to qualitatively assess the presence of GMOs. One
      example is the commercially available DualChip GMO (Eppendorf, Germany;
      http://www.eppendorf-biochip.com), which is the only GMO screening system
      successfully validated in a multicenter study. With use of innovative
      amplification techniques, promising steps have recently been taken to make GMO
      detection with microarrays quantitative.

PMID- 19862508
TI  - Properties of glutamatergic synapses in immature layer Vb  pyramidal neurons:
      coupling of pre- and postsynaptic  maturational states.
AB  - Following initial contact formation, glutamatergic synapses in cortical neurons
      undergo pronounced functional maturation. These maturational events, occurring
      both pre- and postsynaptically, have been well described in the developing
      hippocampus. In this paper, we characterized glutamatergic synapses in immature
      layer Vb pyramidal neurons of the mouse somatosensory cortex during early
      postnatal development. At postnatal day 7, a significant subpopulation of
      glutamatergic synapses exhibited a low release probability that was accompanied
      by strong paired-pulse facilitation of AMPA EPSCs (paired-pulse ratio C > or =
      2). Increasing extracellular Ca(2+) concentration increased release probability
      and led to paired-pulse depression. During further postnatal development, these
      functionally immature synapses disappeared. As shown pharmacologically,these
      synapses expressed postsynaptic NMDA receptors containing NR2B subunits, while
      NMDA receptors with NR2A subunits were lacking. Taken together, a low release
      probability presynaptically was coupled to postsynaptic NR2B signaling. This
      subpopulation of neocortical synapses thus differed from the majority of synapses
      in the developing hippocampus, where high release probability is coupled to NR2B
      signaling. The novel type of functionally immature glutamatergic synapse
      described here might play an important role in early developmental synapse
      elimination and in the activity-dependent refinement of the neocortical synaptic
      microcircuitry.

PMID- 19862509
TI  - Neuroimaging after coma.
AB  - Following coma, some patients will recover wakefulness without signs of
      consciousness (only showing reflex movements, i.e., the vegetative state) or may
      show non-reflex movements but remain without functional communication (i.e., the
      minimally conscious state). Currently, there remains a high rate of misdiagnosis
      of the vegetative state (Schnakers et. al. BMC Neurol, 9:35, 8) and the clinical
      and electrophysiological markers of outcome from the vegetative and minimally
      conscious states remain unsatisfactory. This should incite clinicians to use
      multimodal assessment to detect objective signs of consciousness and validate
      para-clinical prognostic markers in these challenging patients. This review will
      focus on advanced magnetic resonance imaging (MRI) techniques such as magnetic
      resonance spectroscopy, diffusion tensor imaging, and functional MRI (fMRI
      studies in both "activation" and "resting state" conditions) that were recently
      introduced in the assessment of patients with chronic disorders of consciousness.

PMID- 19862511
TI  - Potential therapeutic efficacy of a bactericidal-immunomodulatory fusion peptide
      against methicillin-resistant Staphylococcus aureus skin infection.
AB  - To enhance the potential therapeutic efficacy of an antimicrobial peptide human
      beta-defensin 3, two fusion peptides, a bactericidal-immunomodulatory fusion
      peptide human beta-defensin 3-mannose-binding lectin and a bactericidal
      bactericidal fusion peptide human beta-defensin 3-lysozyme were synthesized and
      the bactericidal activities in vitro and in vivo against methicillin-resistant
      Staphylococcus aureus N315 were demonstrated in this study. Peptide human beta
      defensin 3-lysozyme showed the best bactericidal activity in vitro, but human
      beta-defensin 3-mannose-binding lectin showed a significant improvement in
      angiogenesis and tissue reconstruction. Our results illustrated that outstanding
      bactericidal activity in vitro is not essential in the development of
      antimicrobial peptides. Fusion strategy and immunomodulatory factors should be
      utilized in novel antimicrobial peptide development.

PMID- 19862510
TI  - Analysis of HK-2 cells exposed to oxalate and calcium oxalate crystals: proteomic
      insights into the molecular mechanisms of renal injury and stone formation.
AB  - Exposure to high levels of oxalate and calcium oxalate monohydrate (COM) crystals
      is injurious to renal epithelial cells and triggers serial responses related to
      stone formation. Multiple molecules and proteins are involved in this process,
      but previous studies have generally been limited, without an overall
      understanding of protein expression alteration after oxalate and/or crystal
      exposure as well as its role in stone formation. We used proteomic analysis to
      reveal the changes in the proteome of HK-2 cells induced by oxalate and COM
      crystals, so as to provide candidate proteins involved in the molecular
      mechanisms concerning HK-2 cell injury and kidney stone formation. HK-2 cells
      were exposed to oxalate plus COM crystals at different concentrations in various
      samples. Cell viability was determined using a Cell Counting Kit-8 assay kit. For
      proteomic analysis, cells were exposed to oxalate (2 mM) and COM crystals (200
      ug/ml) for 12 h. The proteins were separated by two-dimensional electrophoresis
      and the differentially expressed proteins were identified by liquid
      chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).
      Validation of protein expression was further performed by Western blot analysis.
      Oxalate and COM crystals showed concentration-dependent toxicity on HK-2 cells. A
      total of 12 differentially expressed proteins in HK-2 cells induced by oxalate
      and COM crystals were identified, which were involved in various aspects of
      cellular processes. Our study provides a platform for further studying the
      molecular mechanism of renal epithelial cell injury and kidney stone formation.

PMID- 19862512
TI  - Purification, characterization, and mode of action of a rhamnogalacturonan
      hydrolase from Irpex lacteus, tolerant to an acetylated substrate.
AB  - A novel rhamnogalacturonase (RGase) acting on an acetylated substrate was
      detected in the commercial preparation Driselase, an enzymatic mixture derived
      from the basidiomycete Irpex lacteus. The activity was isolated by hydrophobic
      interaction chromatography, gel filtration, and preparative isoelectric focusing,
      resulting in the isolation of five different rhamnogalacturonan hydrolases
      exhibiting various isoelectric points from 6.2 to 7.7. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and mass spectrometry analyses after trypsin
      cleavage of the five fractions revealed that the five rhamnogalacturonases have a
      molar mass of 55 kDa without any divergences in the identified peptides. The
      RGase with a pI of 7.2 exhibited a pH optimum between 4.5 and 5 and a temperature
      optimum between 40 degrees C and 50 degrees C. Its mode of action was analyzed by
      mass spectrometry of the oligosaccharides produced after hydrolysis of acetylated
      and nonacetylated rhamnogalacturonan. Oligomers esterified by an acetyl group on
      the reducing galacturonic acid residue or fully acetylated were detected in the
      hydrolysate showing that the novel enzyme is able to bind acetylated galacturonic
      acid in its active site.

PMID- 19862513
TI  - An intracellular pH gradient in the anammox bacterium Kuenenia stuttgartiensis as
      evaluated by 31P NMR.
AB  - The cytoplasm of anaerobic ammonium oxidizing (anammox) bacteria consists of
      three compartments separated by membranes. It has been suggested that a proton
      motive force may be generated over the membrane of the innermost compartment, the
      "anammoxosome". 31P nuclear magnetic resonance (NMR) spectroscopy was employed to
      investigate intracellular pH differences in the anammox bacterium Kuenenia
      stuttgartiensis. With in vivo NMR, spectra were recorded of active, highly
      concentrated suspensions of K. stuttgartiensis in a wide-bore NMR tube. At
      different external pH values, two stable and distinct phosphate peaks were
      apparent in the recorded spectra. These peaks were equivalent with pH values of
      7.3 and 6.3 and suggested the presence of a proton motive force over an
      intracytoplasmic membrane in K. stuttgartiensis. This study provides for the
      second time--after discovery of acidocalcisome-like compartments in Agrobacterium
      tumefaciens--evidence for an intracytoplasmic pH gradient in a chemotrophic
      prokaryotic cell.

PMID- 19862514
TI  - Genetic engineering of fungal biocontrol agents to achieve greater efficacy
      against insect pests.
AB  - Molecular biology methods have elucidated pathogenic processes in several fungal
      biocontrol agents including two of the most commonly applied entomopathogenic
      fungi, Metarhizium anisopliae and Beauveria bassiana. In this review, we describe
      how a combination of molecular techniques has: (1) identified and characterized
      genes involved in infection; (2) manipulated the genes of the pathogen to improve
      biocontrol performance; and (3) allowed expression of a neurotoxin from the
      scorpion Androctonus australis. The complete sequencing of four exemplar species
      of entomopathogenic fungi including B. bassiana and M. anisopliae will be
      completed in 2010. Coverage of these genomes will help determine the identity,
      origin, and evolution of traits needed for diverse lifestyles and host switching.
      Such knowledge combined with the precision and malleability of molecular
      techniques will allow design of multiple pathogens with different strategies to
      be used for different ecosystems and avoid the possibility of the host developing
      resistance.

PMID- 19862515
TI  - Hyaluronic acid production is enhanced by the additional co-expression of UDP
      glucose pyrophosphorylase in Lactococcus lactis.
AB  - Hyaluronic acid (HA) production was metabolically engineered in Lactococcus
      lactis by introducing the HA synthetic machinery from the has operon of the
      pathogenic bacterium Streptococcus zooepidemicus. This study shows that the
      insertion of uridine diphosphate (UDP)-glucose pyrophosphorylase (hasC) gene in
      addition to the HA synthase (hasA) and UDP-glucose dehydrogenase (hasB) genes has
      a significant impact on increasing HA production. The recombinant L. lactis
      NZ9000 strain transformed with the plasmid pSJR2 (co-expressing hasA and hasB
      genes only) produced a maximum of 107 mg/l HA in static flask experiments with
      varying initial glucose concentrations, while the corresponding experiments with
      the transformant SJR3 (co-expressing hasA, hasB, and hasC genes) gave a maximum
      yield of 234 mg/l HA. The plasmid cloned with the insertion of the full has
      operon comprising of five different genes (hasA, hasB, hasC, hasD, and hasE)
      exhibited structural instability. The HA yield was further enhanced in batch
      bioreactor experiments with controlled pH and aeration, and a maximum of 1.8 g/l
      HA was produced by the SJR3 culture.

PMID- 19862516
TI  - Extraction of extracellular polymeric substances (EPS) from anaerobic granular
      sludges: comparison of chemical and physical extraction protocols.
AB  - The characteristics of the extracellular polymeric substances (EPS) extracted
      with nine different extraction protocols from four different types of anaerobic
      granular sludge were studied. The efficiency of four physical (sonication,
      heating, cationic exchange resin (CER), and CER associated with sonication) and
      four chemical (ethylenediaminetetraacetic acid, ethanol, formaldehyde combined
      with heating, or NaOH) EPS extraction methods was compared to a control
      extraction protocols (i.e., centrifugation). The nucleic acid content and the
      protein/polysaccharide ratio of the EPS extracted show that the extraction does
      not induce abnormal cellular lysis. Chemical extraction protocols give the
      highest EPS extraction yields (calculated by the mass ratio between sludges and
      EPS dry weight (DW)). Infrared analyses as well as an extraction yield over 100%
      or organic carbon content over 1 g g(-1) of DW revealed, nevertheless, a carry
      over of the chemical extractants into the EPS extracts. The EPS of the anaerobic
      granular sludges investigated are predominantly composed of humic-like
      substances, proteins, and polysaccharides. The EPS content in each biochemical
      compound varies depending on the sludge type and extraction technique used. Some
      extraction techniques lead to a slightly preferential extraction of some EPS
      compounds, e.g., CER gives a higher protein yield.

PMID- 19862517
TI  - Human biodistribution and radiation dosimetry of 11C-(R)-PK11195, the prototypic
      PET ligand to image inflammation.
AB  - PURPOSE: The positron emission tomography (PET) radiotracer (11)C-(R)-PK11195
      allows the in vivo imaging in humans of the translocator protein 18 kDa (TSPO),
      previously called peripheral benzodiazepine receptor (PBR), a marker of
      inflammation. Despite its widespread use, the radiation burden associated with
      (11)C-(R)-PK11195 in humans is not known. To examine this, we performed dynamic
      whole-body imaging with PET and (11)C-(R)-PK11195 in healthy humans. METHODS:
      Five healthy male volunteers were scanned with PET and (11)C-(R)-PK11195, using a
      dynamic whole-body imaging protocol. An organ-specific method was used to measure
      accumulated radioactivity in source organs, and residence times were calculated
      as areas under the curve of time-activity curves expressed as percentage of
      injected radioactivity. Residence times were used as input for OLINDA/EXM 1.0
      software to model the equivalent organ doses and the effective dose for the 70-kg
      man. RESULTS: After intravenous injection of (11)C-(R)-PK11195, radioactivity
      accumulated in organs rich in TSPO as well as routes of excretion: the
      hepatobiliary system and the urine. The mean effective dose was 4.8 microSv/MBq
      according to International Commission on Radiological Protection (ICRP)
      Publication 60 and 5.1 microSv/MBq according to ICRP Publication 103, and the
      highest equivalent organ doses were observed in the kidneys (14.0 microSv/MBq),
      spleen (12.5 microSv/MBq) and small intestine (12.2 microSv/MBq). CONCLUSION:
      Imaging of TSPO with PET using (11)C-(R)-PK11195 is associated with modest
      radiation exposure, similar in magnitude to most other (11)C-labelled PET
      tracers, suggesting feasibility of (11)C-(R)-PK11195 imaging in clinical human
      studies involving multiple scans in the same subjects per year.

PMID- 19862518
TI  - Early FDG-PET response-adapted risk stratification and further therapeutic
      decision-making in lymphoma: will this replace the established prognostic indices
      and be the standard-of-care in clinical management?

PMID- 19862519
TI  - Clinical value of 18F-fluorodihydroxyphenylalanine positron emission
      tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma.
AB  - PURPOSE: In detecting pheochromocytoma (PHEO), positron emission tomography (PET)
      with the radiolabelled amine precursor (18)F-fluorodihydroxyphenylalanine ((18)F
      DOPA) offers excellent specificity, while computed tomography (CT) provides high
      sensitivity and ability to localize lesions; therefore, the combination of these
      modalities could be advantageous in this setting. The aim of this study was to
      investigate whether combined (18)F-DOPA PET/CT more accurately detects and
      localizes PHEO lesions than does each modality alone. METHODS: (18)F-DOPA PET, CT
      and (18)F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic
      scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome
      associated PHEO were reviewed retrospectively in randomized sequence. Two blinded
      observers scored the images regarding the likelihood of PHEO being present and
      localizable. Results were correlated with subsequent clinical history and, when
      available, histology. RESULTS: Of the 19 lesions detected by all three
      modalities, PET identified each as positive for PHEO, but was unable to
      definitively localize 15 of 19 (79%). CT could definitively localize all 19
      lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%)
      lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which
      was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT
      scans were all 19 lesions accurately characterized and localized. On a per
      patient basis, the sensitivity of (18)F-DOPA PET/CT for PHEO was 100% and the
      specificity 88%, with a 100% positive predictive value and an 88% negative
      predictive value. CONCLUSION: (18)F-DOPA PET/CT more accurately diagnoses and
      localizes adrenal and extra-adrenal masses suspicious for PHEO than do (18)F-DOPA
      PET or CT alone.

PMID- 19862520
TI  - Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and
      Parkinson's disease.
AB  - PURPOSE: To determine clinical predictors and accuracy of (123)I-FP-CIT SPECT
      imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson's
      disease (PD). METHODS: Several clinical features and (123)I-FP-CIT SPECT images
      in 32 patients with DIP, 25 patients with PD unmasked by antidopaminergic drugs
      (PDu) and 22 patients with PD without a previous history of antidopaminergic
      treatment (PDc) were retrospectively evaluated. RESULTS: DIP and PD shared all
      clinical features except symmetry of parkinsonian signs which was more frequently
      observed in patients with DIP (46.9%) than in patients with PDu (16.0%, p<0.05)
      or PDc (4.5%, p<0.01). Qualitatively (123)I-FP-CIT SPECT images were normal in 29
      patients with DIP (90.6%) and abnormal in all patients with PD, and this imaging
      technique showed high levels of accuracy. CONCLUSION: DIP and PD are difficult to
      differentiate based on clinical signs. The precision of clinical diagnosis could
      be reliably enhanced by (123)I-FP-CIT SPECT imaging.

PMID- 19862522
TI  - Cancer testis antigens and melanoma stem cells: new promises for therapeutic
      intervention.

PMID- 19862523
TI  - Nuclear factor kappaB-activated monocytes contribute to pancreatic cancer
      progression through the production of Shh.
AB  - Recently, it was reported that Hh signaling is activated in tumor stromal cells
      but not in tumor cells themselves and that stromal cells may play a role in the
      proliferation of cancer cells. This suggests the possibility that stromal cells
      have an important role in the proliferation of tumor cells that may be mediated
      through Hh signaling. In this report, we present for the first time that
      inflammation-stimulated monocytes produce Shh through activation of the NF-kappaB
      signaling pathway, and that the Shh produced promotes the proliferation of
      pancreatic cancer cells in a paracrine manner through Hh signaling.

PMID- 19862524
TI  - Advances in cellular therapy: 5th International Symposium on the clinical use of
      cellular products, 19 and 20 March 2009, Nurnberg, Germany.

PMID- 19862525
TI  - Arthroscopic treatment for malunions of the proximal humeral greater tuberosity.
AB  - The purpose of this article was to report an arthroscopic treatment method for
      greater tuberosity malunion. Eight patients with malunion of the greater
      tuberosity were treated by arthroscopic acromioplasty, detachment of rotator
      cuff, tuberoplasty of the greater tuberosity and repair of the rotator cuff. On
      the basis of the UCLA rating scale, the overall score increased from 11.1 (range
      9-14) to 30.2 (range 25-35) postoperatively, with one excellent result, six good
      results, and one poor result. All patients had less pain than preoperatively.
      Full activity level was achieved in two patients, five patients had only slight
      functional restriction, and one patient had mild limitation in activities of
      daily living. Seven patients returned to their previous occupations without
      restrictions. One patient did not return to work because of residual upper
      extremity weakness. We conclude that arthroscopic tuberoplasty is a good method
      for the treatment of greater tuberosity malunion.

PMID- 19862526
TI  - Synergistic activity of nilotinib and established chemotherapeutic drugs in
      imatinib-sensitive and -resistant BCR-ABL-positive cells.
AB  - We investigated various combination treatment regimens employing nilotinib with
      established chemotherapeutic agents (daunorubicin, mitoxantrone, etoposide and
      cytarabine) in imatinib-sensitive and -resistant BCR-ABL-positive cells.
      Mitoxantrone or cytarabine showed synergism (CI < 1) in combination with
      nilotinib in imatinib-sensitive LAMA84 cells, whereas in imatinib-resistant
      LAMA84-R cells synergistic effects could be assessed for daunorubicin,
      mitoxantrone and etoposide when combined with nilotinib. In both imatinib
      sensitive and -resistant K562 cells daunorubicin, mitoxantrone and etoposide
      demonstrated synergism in combination with nilotinib. Moreover, both daunorubicin
      and mitoxantrone led to synergistic antiproliferative effects when combined with
      nilotinib in imatinib-resistant Ba/F3 cells carrying point mutations in the ABL
      TK domain (E255K, E255V and T315I). Annexin V/propidium iodide staining revealed
      a significant enhancement of nilotinib-induced apoptosis in imatinib-resistant
      Ba/F3T315I and LAMA84-R cells upon combination with daunorubicin and
      mitoxantrone, respectively. Our results demonstrate the efficacy of combination
      treatment regimens employing nilotinib and established chemotherapeutic agents in
      improving antileukemic effects in imatinib-sensitive and imatinib-resistant
      cells. This may be the foundation for further study on the potential of the
      applied combinations in a clinical setting.

PMID- 19862527
TI  - [Identification of VHL-associated changes in clear cell renal carcinoma: the
      application of combined genome and expression analyses].
AB  - Sporadic renal cell carcinoma (RCC) represents a heterogeneous tumor, which is
      traditionally classified into subtypes based on morphological criteria. In recent
      years high-throughput molecular analyses have been able to identify genomic and
      proteomic alterations in tumor cells. These markers are the basis for a molecular
      classification of RCC and bear prognostic value. However, an isolated
      consideration of genomic and proteomic alterations prevents deeper insights into
      the complex processes of carcinogenesis. Here we summarize recent studies
      focussing on this aspect of RCC and present a systems biology concept for the
      identification of novel tumor markers. These could be applied to improve future
      diagnosis and therapy of RCC.

PMID- 19862528
TI  - Incidence and predictors of osteonecrosis among cyclosporin- or tacrolimus
      treated renal allograft recipients.
AB  - The aim of this study was to investigate the incidence of osteonecrosis of the
      hip and knee among renal allograft recipients treated with cyclosporin- or
      tacrolimus-based immunosuppressive regimens and its predictors focusing on the
      first 8 weeks after transplantation. The subjects were 232 renal allograft
      recipients who had MRI for osteonecrosis of the hip and knee 3 months or longer
      after transplant. The following potential predictors of osteonecrosis were tested
      using univariate and multivariate logistic regression analyses: age, gender, body
      weight, body mass index, duration on dialysis before transplant, number of human
      leukocyte antigen mismatches, ABO mismatches, type of transplanted kidney,
      immunosuppressive regimen, cumulative steroid dose and steroid pulses, incidence
      of acute rejection, and delayed graft function, defined as requiring dialyses in
      the first week. Evidence of osteonecrosis was visible on the MRI of 11 recipients
      (4.7%, 95% confidence interval 2.4-8.3). Univariate and multivariate logistic
      regression analyses indicated that delayed graft function was the most important
      predictor of osteonecrosis. In conclusion, we found a lower incidence of
      osteonecrosis of the hip and knee in renal allograft recipients treated with
      cyclosporin or tacrolimus. In the patients treated with improved
      immunosuppressive regimens, delayed graft function was a significant early
      predictor of osteonecrosis.

PMID- 19862529
TI  - Recurrent pneumothorax associated with pulmonary nodules after leflunomide
      therapy in rheumatoid arthritis: a case report and review of the literature.
AB  - Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterized by
      destructive synovitis and systemic extraarticular involvement. One of the most
      common pulmonary manifestations of RA is rheumatoid nodule. Spontaneous
      pneumothorax also very rare pulmonary finding and could be associated with
      pulmonary nodules. Antirheumatic drugs, methotrexate, leflunomide (LEF),
      infliximab and etanercept, were known as risk factors for developing rheumatoid
      nodule. However, there was no case report of rheumatoid nodule-associated
      pneumothorax with the use of LEF. We report, first, herein a case of 46-year-old
      woman with RA who suffered recurrent spontaneous pneumothorax associated with
      multiple bilateral subpleural cavitary nodules during treatment with LEF. We
      reviewed the cases of LEF-related pulmonary nodules developed in patients with
      RA. Thus, we suggested that pneumothorax can be a rare respiratory fatal
      complication in patients with RA with pulmonary nodules and LEF can be a rare
      cause of these manifestations.

PMID- 19862530
TI  - Clinical and radiological features of Takayasu's arteritis patients in Jordan.
AB  - The prevalence of Takayasu's arteritis (TA) varies greatly among world
      populations, and little is known about this disease in Eastern Mediterranean Arab
      populations. We conducted a retrospective chart review of patients diagnosed with
      TA from 1996 to 2008 at a single large referral center in Jordan. Eight patients
      (seven females, one male) with angiographically diagnosed TA were seen at the
      Jordan University Hospital between 1996 and 2008. All patients were of Arabic
      ethnicity. The age at presentation ranged from 14 to 50 years, and delay in
      diagnosis ranged from 1 to 10 years. Extra-vascular manifestations included
      nodular episcleritis, elevated liver enzymes, erythema nodosum, inflammatory
      bowel-disease-like illness, Raynaud's phenomena, and constitutional symptoms.
      Vascular symptoms included postural dizziness, central nervous system deficits,
      amauroses fugax, and transient ischemic attacks. Aortic arch vessels were
      involved in all patients, the abdominal aorta was involved in five patients, and
      the renal arteries in four patients. Major clinical events including severe
      stroke and cardiac failure were associated with mortality in two patients.
      Treatment with corticosteroids and immunosuppressive agents resulted in
      improvement in five patients with follow-up ranging from 3 to 12 years. In
      conclusion, TA is seen in Arabs, and the clinical spectrum of TA in Arabs in
      Jordan is similar to that reported in other countries. Increased awareness of the
      disease may shorten the time to diagnosis and result in a more reliable estimate
      of disease prevalence.

PMID- 19862531
TI  - Analysis of false-negative results after US-guided 14-gauge core needle breast
      biopsy.
AB  - OBJECTIVES: To determine the false-negative rate and to evaluate the clinical,
      radiologic or histologic features of false-negative results at ultrasound (US)
      guided 14-gauge core needle biopsy (CNB). METHODS: A total of 3,724 masses from
      3,308 women who had undergone US-guided 14-gauge CNB and who had a rebiopsy or at
      least 2 years' follow-up were included. The histology of CNB was correlated with
      the rebiopsy or long-term imaging follow-up. In cases of missed cancer, the time
      interval between CNB and rebiopsy, the reasons for rebiopsy, and the procedural
      or lesion characteristics were analysed. RESULTS: Of 1,706 benign CNBs, 50
      additional malignancies were found at excision (false-negative rate, 2.5% of
      1,982 with a final diagnosis of malignancy). Of 50 false negatives, 41 were found
      immediately of which 28 had rebiopsy because of imaging-histological discordance.
      Regarding the frequency of malignancy according to the reasons for rebiopsy,
      suspicious imaging finding (24%) showed significantly higher frequency than
      suspicious clinical findings or request (1%). Regarding the characteristics
      except invasiveness, no significant differences in false-negative rates were
      found. CONCLUSIONS: Most false negatives were found immediately and imaging
      histological discordance was the most important clue. Careful correlation of
      clinical, radiological and histological results as well as appropriate follow-up
      is essential.

PMID- 19862532
TI  - Correlation of regional distribution and morphological pattern of calcification
      at CT coronary artery calcium scoring with non-calcified plaque formation and
      stenosis.
AB  - OBJECTIVE: To investigate whether regional calcification patterns at CT coronary
      artery calcium scoring (CCS) correlate with stenosis and non-calcified plaque
      formation. METHODS: We studied 106 patients with quantitative catheter
      angiography (QCA), CCS, and coronary CT angiography (cCTA). CCS was determined
      globally and for each artery separately. The morphological pattern of each
      calcification was classified as calcified nodule, shell-like, or diffuse. cCTA
      studies were evaluated for non-calcified plaque. The global and regional CCS and
      the calcification pattern were correlated with stenosis >or=50% and non-calcified
      plaque. RESULTS: A total of 48/106 patients had stenosis >or=50% on QCA. There
      was weak correlation (r = 0.36) of the global CCS with stenosis. Correlation was
      stronger per vessel (r = 0.55-r = 0.67). Shell-like and diffuse calcifications
      were significantly (p = 0.0001) more frequently associated with >or=50% stenosis
      and non-calcified plaque (p = 0.04) than calcified nodules. CONCLUSION: As shown
      before, the global CCS does not correlate well with stenosis. However, regional
      calcium distribution and specific patterns of calcification are correlated with
      stenosis and non-calcified plaque. Thus, the specificity of CT calcium scoring
      for identifying individuals with obstructive disease could be improved by vessel
      based rather than global quantification of calcium and by differentiating
      specific morphological patterns of calcification.

PMID- 19862533
TI  - Usefulness of diffusion-weighted MR imaging in the evaluation of pulmonary
      lesions.
AB  - PURPOSE: The role of diffusion-weighted MR imaging (DWI) in the differential
      diagnosis of pulmonary malignant tumours and solid benign lesions was
      investigated. METHODS: Sixty-two patients with 66 lesions underwent conventional
      MRI and DWI (diffusion factor of 0 and 500 s/mm(2)) examinations with 1.5-T MRI.
      The signal intensity of DWI images was observed and the apparent diffusion
      coefficient (ADC) values of the lesions were measured. Statistical analyses were
      performed with the independent samples t test, Pearson's chi-square test and
      receiver operating characteristic (ROC) analysis. RESULTS: The signal intensities
      of pulmonary malignant tumours and solid benign lesions were not significantly
      different, but the ADC value of benign lesions was statistically higher than that
      of malignant tumours (p = 0.001). By ROC analysis, the optimal threshold of ADC
      was 1.400 x 10(-3) mm(2)/s and the sensitivity and specificity were 83.3% and
      74.1%, respectively. There were statistical differences between small cell
      carcinoma (SCLC) and non-small cell carcinoma (NSCLC) as well; the former was
      lower than the latter (p = 0.007). CONCLUSION: Our data indicate that
      quantitative analysis of ADC values may help diagnose or distinguish pulmonary
      lesions, and it also provides a promising method for characterising the pulmonary
      masses.

PMID- 19862534
TI  - Computer-assisted detection of pulmonary embolism: evaluation of pulmonary CT
      angiograms performed in an on-call setting.
AB  - PURPOSE: The purpose of the study was to assess the stand-alone performance of
      computer-assisted detection (CAD) for evaluation of pulmonary CT angiograms
      (CTPA) performed in an on-call setting. METHODS: In this institutional review
      board-approved study, we retrospectively included 292 consecutive CTPA performed
      during night shifts and weekends over a period of 16 months. Original reports
      were compared with a dedicated CAD system for pulmonary emboli (PE). A reference
      standard for the presence of PE was established using independent evaluation by
      two readers and consultation of a third experienced radiologist in discordant
      cases. RESULTS: Original reports had described 225 negative studies and 67
      positive studies for PE. CAD found PE in seven patients originally reported as
      negative but identified by independent evaluation: emboli were located in
      segmental (n = 2) and subsegmental arteries (n = 5). The negative predictive
      value (NPV) of the CAD algorithm was 92% (44/48). On average there were 4.7 false
      positives (FP) per examination (median 2, range 0-42). In 72% of studies <or=5 FP
      were found, 13% of studies had >or=10 FP. CONCLUSION: CAD identified small emboli
      originally missed under clinical conditions and found 93% of the isolated
      subsegmental emboli. On average there were 4.7 FP per examination.

PMID- 19862536
TI  - The correlations of incontinence-related quality of life measures with symptom
      severity and pathophysiology in women with primary stress urinary incontinence.
AB  - PURPOSE: We sought to explore the correlations of incontinence-related quality of
      life (QoL) measures with the symptom severity and pathophysiological factors for
      female stress urinary incontinence (SUI). METHODS: We retrospectively reviewed
      the records of 707 women who had primary SUI. Clinical data for analysis included
      Ingelman-Sundberg scales, 1-h pad tests, incontinence-related QoL questionnaires
      comprising short forms of the Urogenital Distress Inventory (UDI-6) and
      Incontinence Impact Questionnaire (IIQ-7), ultrasound assessment of urethral
      support and urethral sphincter function determined by maximum urethral closure
      pressure and Valsalva leak point pressure. The correlations of incontinence
      related QoL, measured by UDI-6 and IIQ-7 questionnaires, with the independent
      variables such as Ingelman-Sundberg scales, 1-h pad tests, urethral support and
      urethral sphincter function were investigated. RESULTS: The scores of item 3 of
      UDI-6 as well as the sum scores of UDI-6 and IIQ-7 had significant correlation
      with incontinence severity assessed by Ingelman-Sundberg scales and 1-h pad
      tests. However, only the scores of item 3 of UDI-6 were significantly correlated
      with the presence of bladder neck funneling on ultrasound and maximum urethral
      closure pressure. No correlations exist between sum scores of UDI-6 or IIQ-7 and
      the pathophysiological factors of SUI. CONCLUSIONS: Urogenital Distress Inventory
      6 and IIQ-7 play important and complementary roles in comprehensive assessment
      for SUI, but are not identical to the pathophysiological factors.

PMID- 19862535
TI  - Utility of vaginal and rectal contrast medium in MRI for the detection of deep
      pelvic endometriosis.
AB  - OBJECTIVE: To study the sensitivity of MRI performed utilising vaginal and rectal
      opacification with ultrasound gel in the detection of deep pelvic endometriosis.
      MATERIAL AND METHODS: This was a prospective monocentric study. All patients
      evaluated by the gynaecologist for pelvic pain, endometriosis or infertility were
      included. Axial and sagittal T2-weighted images were performed both with and
      without vaginal and rectal opacification with ultrasound gel. Three radiologists,
      all blinded, interpreted the images with a minimum of 15 days between the two
      readings. MRI performance with and without vaginal and rectal opacification was
      evaluated by calculating sensitivity, specificity and both positive and negative
      predictive values. RESULTS: Seventy-eight patients were included. Among these, 31
      patients had deep pelvic endometriosis of which 24 were confirmed by laparoscopy.
      Seventy-six locations of deep pelvic endometriosis were discovered on MRI. For
      the three reviewers there was a significant improvement in sensitivity between
      pre- and post-contrast MRI (p < 0.0002). CONCLUSION: Opacification of the vagina
      and rectum significantly improved the sensitivity of MRI for the detection of
      deep pelvic endometriosis by expanding the vagina and rectum, thus allowing
      better delineation of the pelvic organs. This was especially apparent for lesions
      localised to the vagina and rectovaginal septum.

PMID- 19862537
TI  - Prunella vulgaris extract and rosmarinic acid prevent UVB-induced DNA damage and
      oxidative stress in HaCaT keratinocytes.
AB  - Solar radiation is a very important exogenous factor in skin pathogenesis and can
      lead to the development of a number of skin disorders. UVB irradiation is known
      to induce oxidative stress, inflammation and especially DNA lesions in exposed
      cells. It is important, therefore, to identify agents that can offer protection
      against UVB-caused skin damage. Natural compounds have been studied for their
      possible ability to control/modulate various lifestyle-related diseases. The
      application of plant compounds/extracts with screening, antioxidant and anti
      inflammatory activities may also successfully protect the skin against UV-caused
      injury. We assessed the potency of Prunella vulgaris extract (PVE) and its main
      phenolic acid component, rosmarinic acid (RA), to suppress UVB-induced (295-315
      nm) alterations to human keratinocytes HaCaT using a solar simulator. Pre- and
      post-treatment of HaCaT cells with PVE (5-50 mg/l) and RA (0.18-1.8 mg/l) reduced
      breakage together with the apoptotic process. PVE and RA also significantly
      eliminated ROS production and diminished IL-6 release. Taken together, both PVE
      and RA prevent UVB-caused injury to keratinocytes. However their efficacy needs
      to be demonstrated in vivo.

PMID- 19862538
TI  - Intraoperative evaluation of myometrial invasion and histological type and grade
      in endometrial cancer: diagnostic value of frozen section.
AB  - PURPOSE: We have conducted a retrospective, comparative analysis of the accuracy
      of preoperative diagnosis and frozen section diagnosis relative to postoperative
      diagnosis. METHODS: Subjects consisted of 168 patients with endometrial cancer,
      and frozen section was also performed. The diagnostic accuracy and the under
      diagnosis rates in regard to both the myometrial invasion (MI) and the
      histological type and grade (HTG) were determined. RESULTS: The diagnostic
      accuracy rate for preoperative HTG and MI were 64.3 and 54.8%, while the under
      diagnosis rate was 25.0 and 35.7%. In contrast, the corresponding diagnostic
      accuracy rate for frozen HTG and MI were 84.5 and 85.7%, while under-diagnosis
      was 9.5 and 9.5%. Statistical analysis showed that the diagnostic accuracy rate
      for HTG and MI were significantly higher with frozen section diagnosis than with
      preoperative diagnosis (P<0.0001) and the under-diagnosis rate for HTG and MI
      were significantly lower with frozen section diagnosis than with preoperative
      diagnosis (P<0.0001). CONCLUSIONS: Frozen section diagnosis was clearly more
      effective than preoperative diagnosis involving MRI as a basis for deciding the
      operative technique for endometrial cancer.

PMID- 19862539
TI  - Differential expression of fibulins in the uterosacral ligaments of women with
      uterine prolapse.
AB  - PURPOSE: To compare fibulin-3 (FIB-3) and fibulin-5 (FIB-5) expressions in
      uterosacral ligaments (USL) of women with and without uterine prolapse. STUDY
      DESIGN: USL were sampled in a standardized fashion from women with (n = 8) or
      without (n = 8) uterine prolapse. Quantitative Real-Time PCR was performed to
      measure mRNA and immunohistochemistry to assess protein expression. RESULTS: FIB
      3 mRNA expression and FIB-3 staining intensity was similar in the USL of women
      with and without uterine prolapse {[(FIB-3 mean +/- SD mRNA relative units) 0.45
      +/- 0.41 vs. 0.46 +/- 0.82, NS] and [Intensity score, median (range), 1(0-1) vs.
      1(0-1), NS]}. Both FIB-5 mRNA expression and FIB-5 staining intensity was
      significantly decreased in USL from women with uterine prolapse compared to women
      without prolapse {[(FIB-5 mean +/- SD mRNA relative units) 0.07 +/- 0.02 vs. 0.26
      +/- 0.20, P = 0.02] and [Intensity score, median (range), 0(0-2) vs. 3(2-3), P =
      0.002]}. CONCLUSION: FIB-5 expression is decreased in USL of women with uterine
      prolapse.

PMID- 19862540
TI  - Is increased maternal endothelin-1 concentration associated with neonatal
      asphyxia and preterm delivery in intrahepatic cholestasis of pregnancy?
AB  - OBJECTIVES: To evaluate plasma endothelin-1 (ET-1) and fetuin-A concentrations in
      women with intrahepatic cholestasis of pregnancy (ICP) and to determine whether
      there is any association between these parameters and fetal asphyxia. METHODS: We
      carried out a prospective case-control study consisting of 32 women with ICP at
      third trimester of pregnancy and 32 pregnant women without ICP. Blood samples
      from maternal peripheral venous circulation were collected and ET-1 and fetuin-A
      levels were determined from the plasma samples. Pulse-wave Doppler and Apgar
      scores were also recorded. RESULTS: ET-1 concentrations were significantly higher
      in ICP patients. No difference was observed in fetuin-A levels between the two
      groups. Six newborns were declared as asphyctic (APGAR score at the 5 min <7).
      Maternal ET-1 levels did not correlate with the APGAR score at 5 min, total bile
      acid (TBA) and umbilical artery systolic/diastolic ratio with ICP patients. TBA
      levels were positively correlated with umbilical artery systolic/diastolic ratio
      negatively correlated with APGAR score at the 1' and 5'-Apgar score in all
      subjects. Plasma ET-1 concentration was higher in the preterm neonates of mothers
      with ICP compared with normal term neonates of mothers. CONCLUSIONS: Although
      these data did not show evidence that maternal ET-1 would be associated with
      fetal distress, we can speculate that maternal ET-1 may be playing a role in the
      underlying pathology regarding microvascular dysfunction especially in the
      preterm neonates of mothers with ICP. Elevated TBA levels may increase the risk
      of asphyxia whereas fetuin-a (as an anti-inflammation marker) does not seem to
      have effect in women with ICP.

PMID- 19862541
TI  - Transobturator adjustable tape (TOA) in female stress urinary incontinence
      associated with low maximal urethral closure pressure.
AB  - PURPOSE: To determine the success rate of transobturator adjustable tape (TOA,
      Agency for Medical Innovations, A.M.I., Austria) in stress urinary incontinent
      patients with maximal urethral closure pressure (MUCP) < or =20 cm H(2)O compared
      to those with MUCP >20 cm H(2)O. MATERIALS AND METHODS: In this retrospective
      study, all female patients with a diagnosis of stress urinary incontinence
      underwent TOA, from September 2005 to August 2007. All patients had preoperative
      multichannel urodynamic tests (cystometry, urethral profile and uroflowmetry).
      During September 2008, patients were contacted by telephone and the validated
      short forms of the Urogenital Distress Inventory (UDI-6) questionnaire and the
      Incontinence Impact Questionnaire (IIQ-7) were administered. RESULTS: The chart
      review identified 146 patients (125 with MUCP >20 cm H(2)O and 21 with MUCP < or
      =20 cm H(2)O) who had undergone TOA and who met the inclusion criteria. Of these,
      121 patients (82.9%) were contacted by telephone. Results showed a very good
      quality of life (score 0-7 in the IIQ-7) in 95.9% of patients. Only two (1.6%)
      patients had persistent significant urine leakage related to physical activity.
      In the MUCP < or =20 cm H(2)O group, 90% of patients could be considered as being
      very satisfied, with a very good quality of life. CONCLUSION: With the TOA
      procedure, the obturator route could be used to treat patients with urinary
      incontinence and also with low MUCP.

PMID- 19862542
TI  - Premature progesterone elevation impairs implantation and live birth rates in
      GnRH-agonist IVF/ICSI cycles.
AB  - INTRODUCTION: Our aim was to investigate the clinical significance of premature
      elevated progesterone levels in women with good ovarian response treated with
      long gonadotropin-releasing hormone agonist (GnRH-a) cycles and IVF. Premature
      elevated progesterone levels refer to a rise in serum progesterone levels on the
      day of human chorionic gonadotrophin (hCG) administration for final oocyte
      maturation above a threshold level, which is usually arbitrarily defined.
      MATERIALS AND METHODS: This is a retrospective case study, which consists of
      1,045 treatment cycles in women with low P/E2 [progesterone (ng/mL) x
      1,000/estradiol (pg/mL)] on the day of hCG. Elevated P levels on the day of hCG
      administration were defined as >1.1 ng/mL. The data of the control group (< or
      =1.1 ng/mL, n = 900 patients) were compared with those of the high P group (>1.1
      ng/mL, n = 145). RESULTS: Compared with the control group, those in the high
      progesterone group had higher levels of estradiol on the day of hCG (3,143 vs.
      2,382 pg/ml) (p: 0.000) and higher numbers of MII oocytes (14.0 and 12.9) (p:
      0.001). The total number of embryos and the number of good-quality embryos
      transferred did not differ significantly between the groups. Implantation rate
      (18.1 vs. 24.4%) (p: 0.008), and live birth rate (27.6 vs. 40%) (p: 0.004), were
      significantly lower in patients with high progesterone levels. OR and 95% CI were
      0.57 (0.39-0.84) for the live birth rate. CONCLUSION: In women stimulated with
      GnRHa and hMG/FSH for IVF, elevated serum progesterone levels on the day of hCG
      administration were associated with diminished implantation rates and live birth
      rates regardless of ovarian reserve.

PMID- 19862543
TI  - Modified intratympanic treatment for idiopathic sudden sensorineural hearing
      loss.
AB  - Steroids are the only proven drugs in the treatment for idiopathic sudden
      sensorineural hearing loss. In the recent studies, it has been suggested that,
      steroids delivered through the intratympanic route obtained higher perilymph
      levels, resulting in better hearing outcomes. The purpose of this study is to
      compare the hearing outcomes of the two routes of steroid treatment:
      intratympanic route and systemic route. In this prospective study, 60 consecutive
      patients with idiopathic sensorineural hearing loss treated between January 2005
      and September 2008 were enrolled: 29 were in the intratympanic steroid group
      (ITSG) and 31 were in the systemic steroid group (SSG). In the ITSG, 5
      intratympanic injections of dexamethasone were performed with the dose of 4
      mg/ml, consecutively. Oral methylprednisolone was given at the dose of 1 mg/kg,
      tapered every 2 days and stopped at 10 days, in the SSG. The pure tone averages
      (PTA), speech discrimination scores (SDS) and the percentage of the patients who
      made an improvement more than 10 dB were analyzed on the tenth day and 2 months
      after the treatment statistically. The improvement in PTA on tenth day and second
      month after treatment was 31.38 and 37.55 dB, in the ITSG and 19.35 and 20.68 dB
      in the SSG, respectively. The improvement in SDS in the same time period was
      35.24 and 37.52% in the ITSG and 20.13 and 19.61% in the SSG, respectively. Also,
      25 of the 29 patients (86.2%) in the ITSG and 16 of the 31 patients (51.6%) in
      the SSG made an improvement more than 10 dB on PTA in the second month control.
      Intratympanic steroids gave better hearing results than systemic steroids with no
      systemic side effects. Studies with more sample sizes will identify the best
      steroid for injection, application time, frequency and dose.

PMID- 19862544
TI  - Three-dimensional imaging of the larynx for pre-operative planning of laryngeal
      framework surgery.
AB  - Modern laryngeal framework surgery (LFS) requires an exact understanding of the
      laryngeal biomechanics and precise pre-operative planning, for which bi-planar
      imaging is not sufficient. The aim of the study was to test whether MIMICS, a
      commercially available software package for three-dimensional (3D) rendering of
      high-resolution computerised tomography (HRCT), is suitable for 3D imaging of the
      larynx, analysis of laryngeal biomechanics and pre-operative planning. We
      examined four cadaver larynx and one patient larynx. In the five larynges, all
      relevant structures and landmarks could be 3D visualised. Superimposing of two
      HRCT scans shows that when the arytenoids move from 'respiration' to 'phonation',
      they perform a rotating, translating and tilting motion. Moreover, we could
      demonstrate that the vocal fold elongates by 7% with cricothyroid approximation.
      We conclude that MIMCS is well suited for 3D imaging of the larynx, analysis of
      laryngeal biomechanics and pre-operative planning of LFS procedures.

PMID- 19862545
TI  - Review and meta-analysis of epidemiological associations between low/moderate
      doses of ionizing radiation and circulatory disease risks, and their possible
      mechanisms.
AB  - Although the link between high doses of ionizing radiation and damage to the
      heart and coronary arteries has been well established for some time, the
      association between lower-dose exposures and late occurring cardiovascular
      disease has only recently begun to emerge, and is still controversial. In this
      paper, we extend an earlier systematic review by Little et al. on the
      epidemiological evidence for associations between low and moderate doses of
      ionizing radiation exposure and late occurring blood circulatory system disease.
      Excess relative risks per unit dose in epidemiological studies vary over at least
      two orders of magnitude, possibly a result of confounding and effect modification
      by well-known (but unobserved) risk factors, and there is statistically
      significant (p < 0.00001) heterogeneity between the risks. This heterogeneity is
      reduced, but remains significant, if adjustments are made for the effects of
      fractionated delivery or if there is stratification by endpoint (cardiovascular
      disease vs. stroke, morbidity vs. mortality). One possible biological mechanism
      is damage to endothelial cells and subsequent induction of an inflammatory
      response, although it seems unlikely that this would extend to low-dose and low
      dose-rate exposure. A recent paper of Little et al. proposed an arguably more
      plausible mechanism for fractionated low-dose effects, based on monocyte cell
      killing in the intima. Although the predictions of the model are consistent with
      the epidemiological data, the experimental predictions made have yet to be
      tested. Further epidemiological and biological evidence will allow a firmer
      conclusion to be drawn.

PMID- 19862547
TI  - Influence of nonthermal baroreceptor modulation of heat loss responses during
      uncompensable heat stress.
AB  - We evaluated the hypothesis that with increasing levels of hyperthermia, thermal
      influences would predominate over nonthermal baroreceptor control of cutaneous
      vascular conductance (CVC) and local sweat rate (LSR). On separate days, eight
      male participants were positioned in either an upright seated posture (URS) or a
      15 degrees head-down tilt (HDT) posture in a thermoneutral condition and during
      passive heating, until mean body temperature (T(body)) increased by 1.5 degrees
      C. Hemodynamic [heart rate (HR), cardiac output, mean arterial pressure (MAP)]
      and thermal responses [T(re), CVC, LSR] were measured continuously. MAP showed a
      gradual decrease in the early- to mid-stages of heating for both HDT and URS. At
      a T(body) > 0.6 degrees C, MAP achieved a stable, albeit reduced level from
      baseline resting for the duration of the heating, whereas MAP decreased
      significantly throughout the heating period in the URS position (p < 0.001). CVC
      increased rapidly in the early stages of heating and achieved a stable elevated
      level in both HDT and URS at the mid-stage of heating (T(body) increase <or= 0.45
      degrees C) for the duration of the heating period (i.e., to a T(body) increase of
      1.5 degrees C). A similar pattern of response was observed in LSR. A rapid
      increase in LSR was observed in the early- to mid-stages of heating (T(body)
      increase <or= 0.75 degrees C), followed by a slower increase until the end of
      heating. Responses were similar between conditions. We conclude that despite a
      significant nonthermal drive, as evidenced by a significant difference in MAP
      between conditions in the late stages of heating, the thermoeffector activity
      governing CVC and LSR responses are primarily modulated by thermal input.

PMID- 19862548
TI  - MODEM: a multi-agent hierarchical structure to model the human motor control
      system.
AB  - In this study, based on behavioral and neurophysiological facts, a new
      hierarchical multi-agent architecture is proposed to model the human motor
      control system. Performance of the proposed structure is investigated by
      simulating the control of sit to stand movement. To develop the model, concepts
      of mixture of experts, modular structure, and some aspects of equilibrium point
      hypothesis were brought together. We have called this architecture MODularized
      Experts Model (MODEM). Human motor system is modeled at the joint torque level
      and the role of the muscles has been embedded in the function of the joint
      compliance characteristics. The input to the motor system, i.e., the central
      command, is the reciprocal command. At the lower level, there are several experts
      to generate the central command to control the task according to the details of
      the movement. The number of experts depends on the task to be performed. At the
      higher level, a "gate selector" block selects the suitable subordinate expert
      considering the context of the task. Each expert consists of a main controller
      and a predictor as well as several auxiliary modules. The main controller of an
      expert learns to control the performance of a given task by generating
      appropriate central commands under given conditions and/or constraints. The
      auxiliary modules of this expert learn to scrutinize the generated central
      command by the main controller. Auxiliary modules increase their intervention to
      correct the central command if the movement error is increased due to an external
      disturbance. Each auxiliary module acts autonomously and can be interpreted as an
      agent. Each agent is responsible for one joint and, therefore, the number of the
      agents of each expert is equal to the number of joints. Our results indicate that
      this architecture is robust against external disturbances, signal-dependent noise
      in sensory information, and changes in the environment. We also discuss the
      neurophysiological and behavioral basis of the proposed model (MODEM).

PMID- 19862549
TI  - Inhibitory network of spiking neurons may express a sharp peak of synchrony at
      low frequency band.
AB  - Spike synchronization remains an important issue in neuroscience, and inhibitory
      networks are the best candidates to provide such synchrony. Increasing evidence
      indicates that in many brain area inhibitory interneurons of similar properties
      make reciprocal connections. We found that a hybrid, as well as model network,
      consisting of two reciprocally inhibitory spiking neurons may express a peak of
      synchronization in a narrow range of low spiking frequencies in addition to
      classically described plateau of synchrony at a wide range of high frequencies.
      Occurrence of the low frequency peak of synchrony requires a moderate-to-strong
      inhibitory coupling and relatively fast synapses. This novel possibility of
      synchronization in a narrow range of network parameters may have an important
      implication in discrimination and encoding of signals of precise intensity, as
      well as in altering network ability to process information.

PMID- 19862550
TI  - Modelling place memory in crickets.
AB  - Insects can remember and return to a place of interest using the surrounding
      visual cues. In previous experiments, we showed that crickets could home to an
      invisible cool spot in a hot environment. They did so most effectively with a
      natural scene surround, though they were also able to home with distinct
      landmarks or blank walls. Homing was not successful, however, when visual cues
      were removed through a dark control. Here, we compare six different models of
      visual homing using the same visual environments. Only models deemed biologically
      plausible for use by insects were implemented. The average landmark vector model
      and first order differential optic flow are unable to home better than chance in
      at least one of the visual environments. Second order differential optic flow and
      GradDescent on image differences can home better than chance in all visual
      environments, and best in the natural scene environment, but do not
      quantitatively match the distributions of the cricket data. Two models-centre of
      mass average landmark vector and RunDown on image differences-could produce the
      same pattern of results as observed for crickets. Both the models performed best
      using simple binary images and were robust to changes in resolution and image
      smoothing.

PMID- 19862546
TI  - MRN and the race to the break.
AB  - In all living cells, DNA is constantly threatened by both endogenous and
      exogenous agents. In order to protect genetic information, all cells have
      developed a sophisticated network of proteins, which constantly monitor genomic
      integrity. This network, termed the DNA damage response, senses and signals the
      presence of DNA damage to effect numerous biological responses, including DNA
      repair, transient cell cycle arrests ("checkpoints") and apoptosis. The MRN
      complex (MRX in yeast), composed of Mre11, Rad50 and Nbs1 (Xrs2), is a key
      component of the immediate early response to DNA damage, involved in a cross-talk
      between the repair and checkpoint machinery. Using its ability to bind DNA ends,
      it is ideally placed to sense and signal the presence of double strand breaks and
      plays an important role in DNA repair and cellular survival. Here, we summarise
      recent observation on MRN structure, function, regulation and emerging mechanisms
      by which the MRN nano-machinery protects genomic integrity. Finally, we discuss
      the biological significance of the unique MRN structure and summarise the
      emerging sequence of early events of the response to double strand breaks
      orchestrated by the MRN complex.

PMID- 19862551
TI  - Estimation of psychomotor delay from the Fitts' law coefficients.
AB  - An intrinsic property of human motor behavior is a trade-off between speed and
      accuracy. This is classically described by Fitts' law, a model derived by
      assuming that the human body has a limited capacity to transmit information in
      organizing motor behavior. However, Fitts' law can also be realized as an
      emergent property of movements generated by delayed feedback. In this article, we
      describe the relationship between the Fitts' law coefficients and the
      physiological parameters of the underlying delayed feedback circuit: the
      relaxation rate or time constant, and the psychomotor delay of the feedback
      process. This relationship is then used to estimate the motor circuit delay of
      several tasks for which Fitts' law data are available in the literature. We
      consistently estimate the delay to be between 0 and 112 ms. A further consequence
      of this model is that not all combinations of slope and Y-intercept in Fitts' law
      are possible when movements are generated by delayed feedback. In fact, it is
      only possible for an observed speed-accuracy trade-off to be generated by delayed
      feedback if the Fitts' law coefficients satisfy -0.482 < or = a/b < or = 3.343
      [bits] where b represents the slope in bits per second and a represents the Y
      intercept in seconds. If we assume human movement is generated by delayed
      feedback, then the Fitts' law coefficients should always be restricted to this
      range of values.

PMID- 19862552
TI  - Encapsulated apocrine papillary carcinoma of the breast--a tumour of uncertain
      malignant potential: report of five cases.
AB  - Five cases of an unusual encapsulated apocrine papillary tumour are reported. All
      presented as cystic masses in the breast of women aged 44-84 years. Imaging
      studies showed a complex cyst often with one or more mural nodules. The key
      histological features are similar to those of classical encapsulated papillary
      carcinoma in that myoepithelial cells were absent within the papillary structures
      and at the periphery of the cyst. All were pure apocrine in type and showed
      variable degrees of cytological atypia and mitotic activity. All lacked evidence
      of malignancy in the breast tissue outside of the lesion. Sentinel lymph node
      biopsies performed in three of the cases were negative for metastases, and all
      have behaved in a benign fashion.

PMID- 19862553
TI  - Food refusal in 1-year-old child.
AB  - This is a case report of a 1-year-old, otherwise healthy, girl who presented with
      the history of refusal of solid foods and vomiting of 1-month duration. She
      underwent upper gastrointestinal endoscopy, which revealed an eye-catching
      endoscopic finding and the cause of her symptoms.

PMID- 19862554
TI  - Congenital mitral regurgitation due to papillary muscle infarction: a case report
      and approach to evaluation.
AB  - Congenital mitral regurgitation is relatively rare. It can be due to congenital
      malformation of the valve apparatus, associated structural heart defects, or
      results from myocardial dysfunction leading to deformation of the valve annulus.
      Hence, careful delineation of the pathologic processes involved in the mechanism
      is critical when evaluating patients presenting with congenital mitral valve
      regurgitation. Congenital anomalies of the coronary system are one of the serious
      associations, which needs prompt recognition and treatment to prevent fatal
      complications. We report a case of congenital atresia of left main coronary
      artery in an asymptomatic 8-month-old presenting with an incidental finding of
      mitral valvar regurgitation. Appropriate investigations and management lead to
      restoration of normal coronary blood flow and valve function. This particular
      case illustrates that congenital coronary anomalies may present in an otherwise
      asymptomatic child. It should be considered as one of the possible differential
      diagnosis in unexplained mitral regurgitation. Early recognition and prompt
      surgical treatment can radically modify the prognosis.

PMID- 19862555
TI  - Molecular identification of forensically important blowfly species (Diptera:
      Calliphoridae) from Germany.
AB  - Forensic entomology applies knowledge about the behaviour and ecology of insects
      associated to corpses to homicide investigations. It is possible to calculate a
      minimum post-mortem interval by determining the age of the oldest blowfly larvae
      feeding on a corpse. The growth rate of the larvae is highly dependent on
      temperature and also varies between the different blowfly species infesting a
      corpse. It is, thus, crucial to correctly identify the species collected from a
      crime scene. To increase the quality of species identification, molecular methods
      were applied to 53 individuals of six different species sampled in Bonn, Germany:
      Calliphora vicina, Calliphora vomitoria, Lucilia caesar, Lucilia sericata,
      Lucilia illustris, and Protophormia terraenovae. We extracted DNA and checked a
      229 bp sequence within the mitochondrial cytochrome oxidase subunit I. The
      sequences of the local flies were aligned to published data of specimens from
      other countries. We also studied the practical value of the analysed DNA region
      for their differentiation. All species were matched correctly by a Basic Local
      Alignment Search Tool (BLAST) search apart from L. caesar and L. illustris.
      Although molecular methods are very useful-especially if it is necessary to
      identify small fragments of insect material or very young larvae-we propose to
      use it only in addition to the conventional methods.

PMID- 19862556
TI  - Genetic variation in PARL influences mitochondrial content.
AB  - Given their involvement in processes necessary for life, mitochondrial damage and
      subsequent dysfunction can lead to a wide range of human diseases. Previous
      studies of both animal models and humans have suggested that presenilins
      associated rhomboid-like protein (PARL) is a key regulator of mitochondrial
      integrity and function, and plays a role in cellular apoptosis. As a surrogate
      measure of mitochondrial integrity, we previously measured mitochondrial content
      in a Caucasian population consisting of large extended pedigrees, with results
      highlighting a substantial genetic component to this trait. To assess the
      influence of variation in the PARL gene on mitochondrial content, we re-sequenced
      6.5 kb of the gene, identifying 16 SNPs and genotyped these in 1,086 Caucasian
      individuals, distributed across 170 families. Statistical genetic analysis
      revealed that one promoter variant, T-191C, exhibited significant effects (after
      correction for multiple testing) on mitochondrial content levels. Comparison of
      the transcription factor binding characteristics of the T-191C promoter SNP by
      EMSA indicates preferential binding of nuclear factors to the T allele,
      suggesting functional variation in PARL expression. These results suggest that
      genetic variation within PARL influences mitochondrial abundance and integrity.

PMID- 19862558
TI  - Spatial pattern of grazing affects influence of herbivores on spatial
      heterogeneity of plants and soils.
AB  - With our enhanced understanding of the factors that determine biodiversity and
      assemblage structure has come increasing acknowledgment that the use of an
      appropriate disturbance regime to maintain spatial heterogeneity is an effective
      conservation technique. A herbivore's behavior affects its disturbance regime
      (size and intensity); this, in turn, may modify the associated spatial
      heterogeneity of plants and soil properties. We examined whether the pattern of
      spatial disturbance created by the Siberian marmot (Marmota sibirica) affects the
      spatial heterogeneity of vegetation and soils at a colony scale on the Mongolian
      steppe. We expected that the difference in management between two types of area
      (protection against hunting marmots vs. hunting allowed) would result in
      different behavioral patterns; therefore, we estimated the patterns of spatial
      disturbance separately in protected and unprotected areas. We then surveyed plant
      communities and soil nutrients in these areas to assess their spatial
      heterogeneity. We found that disturbance of both vegetation and soil was more
      concentrated near marmot burrows in the unprotected area than in the protected
      area. In addition, the degrees of spatial heterogeneity of vegetation and soil
      NO(3)-N were greater in the unprotected area than in the protected area, where
      disturbance was more widely distributed. These results indicate that the spatial
      pattern of disturbance by herbivores affects the spatial heterogeneity of
      vegetation and soil properties through changes in the disturbance regime. Our
      findings also suggest that the intensity of disturbance is more important than
      its size in determining community structure in Mongolian grasslands.

PMID- 19862557
TI  - Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis
      imperfecta.
AB  - Classical osteogenesis imperfecta (OI) is a dominant genetic disorder of
      connective tissue caused by mutations in either of the two genes encoding type I
      collagen, COL1A1 and COL1A2. Recent investigations, however, have generated a new
      paradigm for OI incorporating many of the prototypical features that distinguish
      dominant and recessive conditions, within a type I collagen framework. We and
      others have shown that the long-sought cause of the recessive form of OI, first
      postulated in the Sillence classification, lies in defects in the genes encoding
      cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1 (P3H1/LEPRE1).
      Together with cyclophilin B (PPIB), CRTAP and P3H1 comprise the collagen prolyl 3
      hydroxylation complex, which catalyzes a specific posttranslational modification
      of types I, II, and V collagen, and may act as a general chaperone. Patients with
      mutations in CRTAP or LEPRE1 have a lethal to severe osteochondrodystrophy that
      overlaps with Sillence types II and III OI but has distinctive features. Infants
      with recessive OI have white sclerae, undertubulation of the long bones, gracile
      ribs without beading, and a small to normal head circumference. Those who survive
      to childhood or the teen years have severe growth deficiency and extreme bone
      fragility. Most causative mutations result in null alleles, with the absence or
      severe reduction of gene transcripts and proteins. As expected, 3-hydroxylation
      of the Pro986 residue is absent or severly reduced, but bone severity and
      survival length do not correlate with the extent of residual hydroxylation.
      Surprisingly, the collagen produced by cells with an absence of Pro986
      hydroxylation has helical overmodification by lysyl hydroxylase and prolyl 4
      hydroxylase, indicating that the folding of the collagen helix has been
      substantially delayed.

PMID- 19862559
TI  - Genetic variation in the response of the weed Ruellia nudiflora (Acanthaceae) to
      arbuscular mycorrhizal fungi.
AB  - The main goal of this work was to test for plant genetic variation in the
      phenotypic plasticity response of the weed Ruellia nudiflora to arbuscular
      mycorrhizal (AM) fungi inoculation. We collected plants in the field, kept them
      under homogeneous conditions inside a nursery, and then collected seeds from
      these parent plants to generate five inbred lines (i.e., genetic families). Half
      of the plants of each inbred line were inoculated with AM fungi while the other
      half were not (controls); a fully crossed experimental design was then used to
      test for the effects of treatment (with or without AM fungi inoculation) and
      inbred line (genetic family). For each plant, we recorded the number of leaves
      produced and the number of days it survived during a 2-month period. Results
      showed a strong positive treatment effect (plastic response to AM fungi
      inoculation) for leaf production and survival. Moreover, in terms of survival,
      the treatment effect differed between genetic families (significant genetic
      family by treatment interaction). These findings indicate that the positive
      effect of AM fungi on plant survival (and potentially also growth) differs across
      plant genotypes and that such condition may contribute to R. nudiflora's capacity
      to colonize new environments.

PMID- 19862560
TI  - How to connect a pedicle screw construct to a Ransford Loop: technical note.
AB  - This technical note describes how a standard pedicle screw system can be
      connected to the 4 mm rod of a Ransford Loop. This report may be of interest for
      spinal surgeons who need to perform similar add-on stabilizations.

PMID- 19862562
TI  - Neuroprotective action of FK-506 (tacrolimus) after seizures induced with
      pilocarpine: quantitative and topographic elemental analysis of brain tissue.
AB  - In the present work, X-ray fluorescence microscopy with a synchrotron source for
      the exciting radiation was applied for topographic and quantitative elemental
      analysis of rat brain tissue in pilocarpine-induced epilepsy and neuroprotection
      with FK-506. The mass per unit area of the elements P, S, Cl, K, Ca, Fe, Cu, Zn,
      Se, Br, and Rb was determined in four fields of the hippocampal formation
      (sectors 1 and 3 of Ammon's horn-CA1, CA3; dentate gyrus; hilus of dentate gyrus)
      and the parietal cortex. The results obtained for epileptic rats treated with FK
      506 (SNF) were compared with data obtained previously for epileptic rats (SNS)
      and a control group. Many statistically significant differences in elemental
      composition were observed between the SNF and SNS groups. Higher mass per unit
      area of P was noticed in CA1 and CA3 regions of the hippocampus of SNF rats in
      comparison with SNS rats. A similar relation was observed for K in all five brain
      areas analyzed. Also, Fe in CA3 and dentate gyrus, Cu in the parietal cortex, and
      Zn in CA3 and in the cortex were present at a higher level in the SNF group in
      comparison with the SNS group. The findings obtained in the present study suggest
      that the neuroprotective action of FK-506 in epileptic rat brain may involve not
      only the inhibition of calcineurin but also blockade of the K(+) channels.

PMID- 19862563
TI  - Role of a novel disulfide bridge within the all-beta fold of soluble Rieske
      proteins.
AB  - Rieske proteins and Rieske ferredoxins are present in the three domains of life
      and are involved in a variety of cellular processes. Despite their functional
      diversity, these small Fe-S proteins contain a highly conserved all-beta fold,
      which harbors a [2Fe-2S] Rieske center. We have identified a novel subtype of
      Rieske ferredoxins present in hyperthermophilic archaea, in which a two-cysteine
      conserved SKTPCX((2-3))C motif is found at the C-terminus. We establish that in
      the Acidianus ambivalens representative, Rieske ferredoxin 2 (RFd2), these
      cysteines form a novel disulfide bond within the Rieske fold, which can be
      selectively broken under mild reducing conditions insufficient to reduce the [2Fe
      2S] cluster or affect the secondary structure of the protein, as shown by visible
      circular dichroism, absorption, and attenuated total reflection Fourier transform
      IR spectroscopies. RFd2 presents all the EPR, visible absorption, and visible
      circular dichroism spectroscopic features of the [2Fe-2S] Rieske center. The
      cluster has a redox potential of +48 mV (25 degrees C and pH 7) and a pK (a) of
      10.1 +/- 0.2. These shift to +77 mV and 8.9 +/- 0.3, respectively, upon reduction
      of the disulfide. RFd2 has a melting temperature near the boiling point of water
      (T(m) = 99 degrees C, pH 7.0), but it becomes destabilized upon disulfide
      reduction (DeltaT(m) = -9 degrees C, DeltaC(m) = -0.7 M guanidinium
      hydrochloride). This example illustrates how the incorporation of an additional
      structural element such as a disulfide bond in a highly conserved fold such as
      that of the Rieske domain may fine-tune the protein for a particular function or
      for increased stability.

PMID- 19862564
TI  - Reversion-inducing cysteine-rich protein with kazal motifs and matrix
      metalloproteinase-9 are prognostic markers in skull base chordomas.
AB  - Prognosis of chordomas is difficult to predict based solely on histological
      findings. The purpose of this study was to assess expressions of reversion
      inducing cysteine-rich protein with kazal motifs (RECK) and matrix
      metalloproteinase (MMP)-2, MMP-9 in skull base chordomas and to find out their
      correlations to outcome. Immunohistochemical study was performed in 19 samples
      (initial, n = 11; recurrent, n = 8) from 11 patients. The correlations among
      expression of RECK, MMP-2, MMP-9, and their prognostic values were analyzed.
      Significant correlation between RECK and MMP-9 was found, but there was no
      correlation found between MMP-2 and MMP-9. Higher MMP-9 expression significantly
      influenced outcome. Furthermore, MMP-9/RECK ratio showed significant correlation
      to outcome, showing their inverse relationship in the disease progress of skull
      base chordoma. RECK and MMP-9 can be valuable markers to predict prognosis in
      skull base chordomas.

PMID- 19862565
TI  - A self-referential default brain state: patterns of coherence, power, and eLORETA
      sources during eyes-closed rest and Transcendental Meditation practice.
AB  - Activation of a default mode network (DMN) including frontal and parietal midline
      structures varies with cognitive load, being more active during low-load tasks
      and less active during high-load tasks requiring executive control. Meditation
      practices entail various degrees of cognitive control. Thus, DMN activation
      patterns could give insight into the nature of meditation practices. This 10-week
      random assignment study compared theta2, alpha1, alpha2, beta1, beta2 and gamma
      EEG coherence, power, and eLORETA cortical sources during eyes-closed rest and
      Transcendental Meditation (TM) practice in 38 male and female college students,
      average age 23.7 years. Significant brainwave differences were seen between
      groups. Compared to eyes-closed rest, TM practice led to higher alpha1 frontal
      log-power, and lower beta1 and gamma frontal and parietal log-power; higher
      frontal and parietal alpha1 interhemispheric coherence and higher frontal and
      frontal-central beta2 intrahemispheric coherence. eLORETA analysis identified
      sources of alpha1 activity in midline cortical regions that overlapped with the
      DMN. Greater activation in areas that overlap the DMN during TM practice suggests
      that meditation practice may lead to a foundational or 'ground' state of cerebral
      functioning that may underlie eyes-closed rest and more focused cognitive
      processes.

PMID- 19862561
TI  - Copper in the brain and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of neurodegenerative disease.
      The brain is particularly vulnerable to oxidative damage induced by unregulated
      redox-active metals such as copper and iron, and the brains of AD patients
      display evidence of metal dyshomeostasis and increased oxidative stress. The
      colocalisation of copper and amyloid beta (Abeta) in the glutamatergic synapse
      during NMDA-receptor-mediated neurotransmission provides a microenvironment
      favouring the abnormal interaction of redox-potent Abeta with copper under
      conditions of copper dysregulation thought to prevail in the AD brain, resulting
      in the formation of neurotoxic soluble Abeta oligomers. Interactions between
      Abeta oligomers and copper can further promote the aggregation of Abeta, which is
      the core component of extracellular amyloid plaques, a central pathological
      hallmark of AD. Copper dysregulation is also implicated in the
      hyperphosphorylation and aggregation of tau, the main component of
      neurofibrillary tangles, which is also a defining pathological hallmark of AD.
      Therefore, tight regulation of neuronal copper homeostasis is essential to the
      integrity of normal brain functions. Therapeutic strategies targeting
      interactions between Abeta, tau and metals to restore copper and metal
      homeostasis are discussed.

PMID- 19862566
TI  - Obstructive sleep apnea in a patient with the Melkersson-Rosenthal syndrome.
AB  - INTRODUCTION: Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown
      etiology. It is characterized by the triad of macrocheilitis, peripheral facial
      palsy, and lingua plicata. CASE REPORT: A 48-year-old nonobese man with a
      diagnosis of MRS and marked macroglossia was evaluated because of clinically
      suspected obstructive sleep apnea (OSA). Established causes of OSA such as
      anatomic abnormalities of the upper airways or the facial skeleton were not
      present in this patient. Furthermore, hypothyroidism and acromegaly were excluded
      as underlying diseases. Polysomnography revealed moderate-to-severe OSA. As the
      swelling of the tongue had been unresponsive to immunosuppressive pharmacotherapy
      and surgery did not seem to be a reasonable therapeutic option, the patient was
      finally treated by continuous positive airway pressure therapy. DISCUSSION: To
      the best of our knowledge, this is the first report of OSA occurring in a patient
      with MRS.

PMID- 19862567
TI  - Thermally induced isomerization of trilinolein and trilinoelaidin at 250 degrees
      C: analysis of products by gas chromatography and infrared spectroscopy.
AB  - The products formed by thermally induced isomerization of trilinolein and
      trilinoelaidin at 250 degrees C were studied by infrared spectroscopy and gas
      chromatography. The triglycerides of the 9c12c and 9t12t fatty acids, linoleic
      and linoelaidic acid respectively, were subjected to thermal treatment under
      nitrogen in glass. The products were removed at regular intervals and analysed by
      infrared spectroscopy using a single reflectance attenuated total internal
      reflectance crystal accessory. Trans-esterification of the products provided the
      corresponding fatty acid methyl esters which were studied by gas chromatography.
      The results show that the samples undergo decomposition and isomerization.
      Thermally induced 9c12c fatty acid (linoleic acid) molecules in the trilinolein
      molecules isomerize into 9c12t, 9t12c and 9t12t isomers. Thermally induced 9t12t
      fatty acid (linoelaidic acid) molecules in the trilinoelaidin molecules isomerize
      into 9c12t, 9t12c and 9c12c isomers. However, the concentration profiles are
      different for these two triglyceride samples. The rates of formation of isomers
      from linoleic acid are higher than the rates of formation of isomers from
      linoelaidic acid. In addition, these two fatty acids also isomerize into
      conjugated linoleic acids (CLAs). The profiles of the CLAs are identical in both
      cases.

PMID- 19862568
TI  - Male lupus: a diagnosis often delayed--a case series and review of the
      literature.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is an auto-immune disease that
      is characterised by autoantibody production. Male lupus is rare, apart from at
      either end of the age spectrum. AIM: In this series, we review the histories of
      six male lupus patients attending our service. RESULTS: Our patients presented in
      middle age and tended to develop haematological abnormalities, renal involvement
      and neurological manifestations which preceded the onset of their skin and joint
      complaints. Our patients accrued damage rapidly and overall did badly. They
      tended to respond sub-optimally to standard treatments. These cases highlight the
      need an increased awareness that male SLE patients present with a wide variety of
      symptoms, and that they accrue damage quickly. There is a need for timely
      diagnosis and appropriate initiation of treatment. This may help avoid
      preventable organ damage and increase the survival of men with SLE.

PMID- 19862569
TI  - Sclerosing angiomatoid nodular transformation of the spleen: CT, MR, PET, and
      99(m)Tc-sulfur colloid SPECT CT findings with gross and histopathological
      correlation.
AB  - Sclerosing angiomatoid nodular transformation (SANT) is a benign, proliferative
      vascular lesion affecting the spleen. Few reports detailing the cross sectional
      and PET appearance of this lesion are available, and the lesion's behavior with
      99(m)Tc-sulfur colloid scintigraphy is previously unreported. Sclerosing nodular
      transformation of the spleen shows increased tracer accumulation on positron
      emission tomography, and a central scar-like appearance with an enhancing capsule
      and radiating septae on CT and MR studies that reflects the gross and
      histopathological features of the lesion may be visible. An understanding of this
      pathological finding may allow prospective recognition of the sclerosing nodular
      transformation of the spleen on cross sectional imaging studies.

PMID- 19862570
TI  - Key concepts for estimating the burden of surgical conditions and the unmet need
      for surgical care.
AB  - BACKGROUND: Surgical care is emerging as a crucial issue in global public health.
      Methodology is needed to assess the impact of surgical care from a public health
      perspective. METHODS: A consensus opinion of a group of surgeons,
      anesthesiologists, and public health experts was established regarding the
      methodology for estimating the burden of surgical conditions and the unmet need
      for surgical care. RESULTS: For purposes of analysis, we define surgical
      conditions as any disease state requiring the expertise of a surgically trained
      provider. Abnormalities resulting from a surgical condition or its treatment are
      termed surgical sequelae. Surgical care is defined as any measure that reduces
      the rates of physical disability or premature death associated with a surgical
      condition. To measure the burden of surgical conditions and unmet need for
      surgical care we propose using cumulative disability-adjusted life-year (DALY)
      curves generated from age-specific population-based data. This conceptual
      framework is based on the premise that surgically associated disability and death
      is determined by the incidence of surgical conditions and the quantity and
      quality of surgical care. The burden of surgical conditions is defined as the
      total disability and premature deaths that would occur in a population should
      there be no surgical care; the unmet need for surgical care is defined as the
      potentially treatable disability and premature deaths due to surgical conditions.
      Burden of surgical conditions should be expressed as DALYs and unmet need as
      potential DALYs avertable. CONCLUSIONS: Methodology is described for estimating
      the burden of surgical conditions and unmet need for surgical care. Using this
      approach it will be feasible to estimate the global burden of surgical conditions
      and help clarify where surgery fits among other global health priorities. These
      methods need to be validated using population-based data.

PMID- 19862571
TI  - Overview of Mammalian Genome special issue on epigenetics.

PMID- 19862572
TI  - Biopsy-proven pulmonary determinants of heart disease.
AB  - Heart disease (HD) can stress the alveolar blood-gas barrier, resulting in
      parenchymal inflammation and remodeling. Patients with HD may therefore display
      any of the symptoms commonly attributed to primary pulmonary disease, although
      tissue documentation of corresponding changes through surgical lung biopsy (SLB)
      is rarely done. Intent on exploring the basis of HD-related alveolar-capillary
      barrier dysfunction, a retrospective analysis of SLB histopathology was conducted
      in patients with clinically diagnosed HD, diffuse pulmonary infiltrates, and no
      evidence of primary pulmonary disease. Patients eligible for the study had a
      clinical diagnosis of heart disease, acute or chronic, and presented with diffuse
      infiltrates on chest X-ray. All qualified subjects (N = 23) who underwent
      diagnostic SLB between January 1982 and December 2005 were subsequently examined.
      Specific biopsy parameters investigated included demonstrable edema, siderophage
      influx, hemorrhage, venous and lymphatic ectasia, vascular sclerosis, capillary
      congestion, and fibroblast proliferation. Based on observed alveolar-capillary
      barrier (ACB) alterations, three main morphologic groups emerged: one group (6
      patients) with alveolar edema; a second group (11 patients) characterized by
      pulmonary congestion; and a final group (6 patients) showing microscopic foci of
      acute ACB lung injury. Alveolar-capillary stress due to acute high-pressure or
      volume overload often manifests as diffuse pulmonary infiltrates with variable
      but generally predictable histopathology. In patients with biopsy-proven alveolar
      edema, pulmonary congestion, or acute microscopic lung injury, the clinician must
      be alert for the possibility of primary heart disease, particularly if the
      patient is elderly or when a history of myocardial, valvular, or coronary
      vascular disease exists.

PMID- 19862573
TI  - Upper-airway cough syndrome with latent eosinophilic bronchitis.
AB  - Upper-airway cough syndrome often coexists with other diseases that elicit
      chronic cough. However, the concomitant conditions are not always relevant to
      chronic cough, which complicates the cause diagnosis of chronic cough. The
      objective of this study was to explore the diagnosis and clinical implication of
      upper-airway cough syndrome with latent eosinophilic bronchitis. Eleven patients
      with upper-airway cough syndrome and latent eosinophilic bronchitis were
      retrospectively analyzed for their clinical manifestations, changes of
      eosinophilia in induced sputum, and cough threshold with capsaicin defined as
      capsaicin concentration that elicits two or more coughs (C2) and five or more
      coughs (C5) between pretreatment and post-treatment. All patients reported a
      history of allergic rhinitis, showed persistent dry cough or small amounts of
      viscid sputum with a time course of 2-60 months (median = 7 months), and
      presented with symptoms and signs of rhinitis, normal lung function, and airway
      responsiveness. Initial eosinophil percentage in induced sputum was 3.5-8.0%.
      Cough disappeared after 2-5 (3 +/- 1) weeks of only oral antihistamine. With
      successful treatment, cough threshold C2 increased from 1.73 +/- 1.45 to 4.43 +/-
      4.50 micromol/L (t = 2.64, P = 0.025) and C5 increased from 2.79 +/- 2.16 to
      10.10 +/- 8.22 micromol/L (t = 3.10, P = 0.011). However, there was no
      significant change of eosinophil percentage in induced sputum (4.8 +/- 1.5% vs.
      4.4 +/- 1.4%, t = 0.84, P = 0.427). Upper-airway cough syndrome with latent
      eosinophilic bronchitis is a unique condition. The recognition of the entity may
      avoid unnecessary use of corticosteroids.

PMID- 19862574
TI  - Glutathione and malondialdehyde levels in late pulmonary complications of sulfur
      mustard intoxication.
AB  - It has been hypothesized that antioxidant and oxidant capacities may be related
      to the severity of obstructive lung impairment in patients with sulfur mustard
      (SM)-induced lung injuries. Our study was designed to measure the level of
      glutathione (GSH) and malondialdehyde (MDA) activities in patients intoxicated
      with SM and to evaluate the relationship between their activity and the severity
      of pulmonary dysfunction. A total of 250 patients with a history of exposure to a
      single high dose of SM gas and also 60 healthy nonsmoking individuals with no
      history of exposure to SM were selected. All patients underwent spirometry; based
      on its indices they were divided into two groups: mild (n = 140) and moderate-to
      severe (n = 110) pulmonary dysfunction. Also, serum GSH and MDA concentration
      measurements were performed for all patients and controls. The mean GSH level in
      controls was 29.85 +/- 3.26 micromol/ml, which was significantly higher than in
      patients with mild and moderate-to-severe pulmonary dysfunction (19.02 +/- 2.36
      and 17.89 +/- 2.16 micromol/ml, respectively). Also, the mean MDA level in
      controls was 0.69 +/- 0.09 micromol/ml, which was significantly lower than in
      patients with mild and moderate-to-severe pulmonary dysfunction (0.74 +/- 0.05
      and 0.75 +/- 0.05 micromol/ml, respectively). There was a weak linear correlation
      between GSH level and some of the pulmonary function indices. On the other hand,
      there was no significant relationship between the MDA level and pulmonary
      indices. Our study confirmed important alterations in the oxidative-antioxidative
      system in patients suffering from SM-induced lung injuries, as shown by a
      decreased serum level of GSH and an increased level of MDA. Individuals with
      moderate-to-severe SM-induced lung injuries show a greater tendency for a
      decreased level of GSH and an increased level of MDA than those with mild
      injuries; however, there is only minimal association between pulmonary function
      parameters and the serum level of MDA and GSH. These findings encourage us to
      examine therapeutic measures to correct such imbalances in future studies.

PMID- 19862575
TI  - Comment on: Visceral obesity may affect oncologic outcome in patients with
      colorectal cancer.

PMID- 19862576
TI  - Taking stock of surgeons' integrity and vitality: why the "three A's" no longer
      tell the whole story.

PMID- 19862577
TI  - From microscopic to macroscopic descriptions of cell migration on growing
      domains.
AB  - Cell migration and growth are essential components of the development of
      multicellular organisms. The role of various cues in directing cell migration is
      widespread, in particular, the role of signals in the environment in the control
      of cell motility and directional guidance. In many cases, especially in
      developmental biology, growth of the domain also plays a large role in the
      distribution of cells and, in some cases, cell or signal distribution may
      actually drive domain growth. There is an almost ubiquitous use of partial
      differential equations (PDEs) for modelling the time evolution of cellular
      density and environmental cues. In the last 20 years, a lot of attention has been
      devoted to connecting macroscopic PDEs with more detailed microscopic models of
      cellular motility, including models of directional sensing and signal
      transduction pathways. However, domain growth is largely omitted in the
      literature. In this paper, individual-based models describing cell movement and
      domain growth are studied, and correspondence with a macroscopic-level PDE
      describing the evolution of cell density is demonstrated. The individual-based
      models are formulated in terms of random walkers on a lattice. Domain growth
      provides an extra mathematical challenge by making the lattice size variable over
      time. A reaction-diffusion master equation formalism is generalised to the case
      of growing lattices and used in the derivation of the macroscopic PDEs.

PMID- 19862578
TI  - The Vermont diabetes information system: a cluster randomized trial of a
      population based decision support system.
AB  - BACKGROUND: Optimal care for patients with diabetes is difficult to achieve in
      clinical practice. OBJECTIVE: To evaluate the impact of a registry and decision
      support system on processes of care, and physiologic control. PARTICIPANTS:
      Randomized trial with clustering at the practice level, involving 7,412 adults
      with diabetes in 64 primary care practices in the Northeast. INTERVENTIONS:
      Provider decision support (reminders for overdue diabetes tests, alerts regarding
      abnormal results, and quarterly population reports with peer comparisons) and
      patient decision support (reminders and alerts). MEASUREMENTS AND MAIN RESULTS:
      Process and physiologic outcomes were evaluated in all subjects. Functional
      status was evaluated in a random patient sample via questionnaire. We used
      multiple logistic regression to quantify the effect, adjusting for clustering and
      potential confounders. Intervention subjects were significantly more likely to
      receive guideline-appropriate testing for cholesterol (OR = 1.39; [95%CI 1.07,
      1.80] P = 0.012), creatinine (OR = 1.40; [95%CI 1.06, 1.84] P = 0.018), and
      proteinuria (OR = 1.74; [95%CI 1.13, 1.69] P = 0.012), but not A1C (OR = 1.17;
      [95% CI 0.80, 1.72] P = 0.43). Rates of control of A1C and LDL cholesterol were
      similar in the two groups. There were no differences in blood pressure, body mass
      index, or functional status. CONCLUSIONS: A chronic disease registry and decision
      support system based on easily obtainable laboratory data was feasible and
      acceptable to patients and providers. This system improved the process of
      laboratory monitoring in primary care, but not physiologic control.

PMID- 19862579
TI  - Update in general internal medicine.

PMID- 19862580
TI  - Teaching health policy to residents--three-year experience with a multi-specialty
      curriculum.
AB  - INTRODUCTION: Most residents have limited education or exposure to health policy
      during residency. AIMS: We developed a course to (1) educate residents on health
      policy topics applicable to daily physician practice; (2) expose residents to
      health policy careers through visits with policy makers and analysts; (3) promote
      personal engagement in health policy. SETTING: Residents registered for a 3-week
      elective offered twice annually through the George Washington University
      Department of Health Policy. PROGRAM DESCRIPTION: The course format includes:
      daily required readings and small-group seminars with policy experts, interactive
      on-site visits with policy makers, and final team presentations to senior faculty
      on topical health policy issues. PROGRAM EVALUATION: One hundred thirty residents
      from 14 specialties have completed the course to date. Seventy completed our post
      course survey. Most participants [59 (84%)] felt the course was very or extremely
      helpful. Participant self-ratings increased from pre- to post-course in overall
      knowledge of health policy [2 (3%) good or excellent before, 58 (83%) after],
      likelihood of teaching policy concepts to peers [20 (25%) vs. 62 (86%)], and
      likelihood of pursuing further health policy training [28 (37%) vs. 56 (82%)].
      CONCLUSIONS: This 3-week elective in health policy improves self-reported
      knowledge and interest in health policy research, advocacy, and teaching.

PMID- 19862581
TI  - Frey procedure for pancreaticopleural fistula.

PMID- 19862582
TI  - Validity of bioelectrical impedance analysis to estimate body composition changes
      after bariatric surgery in premenopausal morbidly women.
AB  - In obese patients, subtle variations of the hydration of soft tissues can
      propagate errors in bioelectrical impedance analysis (BIA) measures of body
      composition. Bioelectrical impedance vector analysis (BIVA) is a useful method to
      evaluate tissue hydration. Laparoscopic adjustable gastric banding (LAGB) is a
      purely restrictive bariatric surgical procedure resulting in lower fat-free mass
      (FFM) loss than other malabsorptive or mixed intervention. The aim of this study
      was to evaluate the 6- and 12-month changes in body composition in a homogeneous
      group of premenopausal morbidly obese women treated by LAGB by comparing the
      results of conventional BIA and BIVA with dual-energy X-ray absorptiometry (DXA)
      method. Forty-five consecutive morbidly obese patients (mean age, 35.3 +/- 9.1
      years; body mass index, 34.5-48.7 kg/m(2)) were prospectively evaluated at the
      Endocrinology Unit of the Department of Molecular and Clinical Endocrinology and
      Oncology. The LAGB device (Lap-Band System; Inamed Health, Santa Barbara, CA,
      USA) was inserted laparoscopically. Soft tissue hydration was evaluated by BIVA;
      fat mass (FM) and FFM were evaluated by BIA (BIA 101 RJL, Akern Bioresearch,
      Firenze, Italy) and by DXA (Hologic QDR 4500A S/N 45622; Hologic Inc., Bedford,
      MA, USA). Pre- and postoperative BIVA vectors indicated a normal hydration in all
      patients. Postoperatively, the excess of body weight loss was mainly due to a
      decrease in FM. The regression analysis of BIA and DXA methods at baseline and at
      the 6- and 12-month follow-up for FM r (2) values were 0.98, 0.94, and 0.99,
      respectively (p < 0.001); FM% r (2) values were 0.91, 0.89, and 0.98,
      respectively (p < 0.001); and FFM r (2) values were 0.87, 0.82, 0.99,
      respectively (p < 0.001). BIA and DXA measurements of body composition exhibit a
      high relative agreement in the study group of normo-hydrated obese subjects. BIA
      tends to overestimate FFM, but this effect is reduced along with the weight loss
      during the follow-up. Under the stable hydration, the BIA method may be useful as
      an alternative to DXA in a selected clinical setting when repeated comparisons of
      body composition are required.

PMID- 19862583
TI  - Gastric perforation as a complication after BioEnterics intragastric balloon
      bariatric treatment in obese patients--synergy of endoscopy and videosurgery.
AB  - The BioEnterics intragastric balloon (BIB) is one of the most common bariatric
      procedures in obese patients in Europe. Associated gastric perforation is a rare,
      yet very dangerous, complication. We report a case of such a complication after
      BioEnterics intragastric balloon insertion in a 60-year-old female patient and
      subsequent cooperation between an endoscopist and bariatric videosurgeon in her
      treatment.

PMID- 19862584
TI  - Feasibility of a supervised inpatient low-calorie diet program for massive weight
      loss prior to RYGB in superobese patients.
AB  - BACKGROUND: This study was undertaken to determine the feasibility of an
      inpatient low-calorie program for a substantial decrease of preoperative weight
      (>10 points in BMI) in superobese patients. METHODS: Five patients were
      hospitalized for an average of 11 weeks and were placed on a low-calorie liquid
      diet (<900 kcal/day) and an exercise program. Following a drop of ten points in
      BMI, they underwent a Roux-en-Y gastric bypass (RYGB). Hemoglobin A1c and lipid
      profiles were obtained at the beginning of the diet, prior to surgery and at the
      last follow-up appointment. Our results were compared to the National Surgical
      Quality Improvement Program (NSQIP) database, which included 1,046 bariatric
      operations performed at VA centers between October 1999 and August 2007. RESULTS:
      All five patients were massively obese men (body mass index (BMI) = 64.3 +/- 2.1
      kg/m(2); 54.7 +/- 2.6 years old; four of five were white) with multiple comorbid
      conditions, which placed them in a substantially higher risk for bariatric
      surgery. Of the four diabetic patients, two were insulin dependent. There was an
      average decrease in BMI by 12.7 points (85.8 +/- 6.0 lb) during the preoperative
      diet period (11 weeks). All patients underwent RYGB without complications. This
      cohort of patients further decreased their BMI by 10.6 points (88.4 +/- 29.4 lb)
      following surgical intervention. The total combined preoperative and
      postoperative excess body weight loss was 89% (10.6-month average follow-up).
      Sleep apnea resolved following gastric bypass but did not improve during the
      preoperative weight loss period. Hypertension, osteoarthritis, and dyslipidemia
      all improved following surgical intervention. Hemoglobin A1c decreased by 1.9%
      during diet-induced weight loss with no further improvement being noted after
      surgery. The two insulin-dependent diabetic patients discontinued insulin therapy
      following surgery. The NSQIP database contained 77 patients with similar
      characteristics to our cohort of patients. The 30-day mortality for this cohort
      of patients was 3.9% with a complication rate of 33.8%. CONCLUSIONS: Massive
      preoperative weight loss is possible to achieve with a liquid protein diet in
      superobese patients greatly facilitating gastric bypass surgery in an otherwise
      high-risk patient population.

PMID- 19862585
TI  - Proximal tibial metaphyseal fractures with severe soft tissue injury: clinical
      and functional results at 2 years.
AB  - BACKGROUND: Controversy exists regarding management of proximal tibial
      metaphyseal fractures with severe soft tissue injury. It is unclear whether limb
      salvage or early amputation results in the best functional and clinical outcomes.
      QUESTIONS/PURPOSE: We hypothesized that in this group of patients, there is no
      difference in functional outcomes, complication rates, clinical outcomes, or
      objective physical function related to the treatment approach. METHODS: We used
      the LEAP study database to perform a retrospective comparative review of a subset
      of patients with proximal tibial metaphyseal fractures (AO/OTA 41A, B, and C)
      with associated severe soft tissue injuries comparing the outcomes of patients
      who were treated with either limb salvage or amputation. RESULTS: Although there
      were major differences in clinical and functional outcomes based on patients'
      sociodemographics at 2 years, no differences in clinical or functional outcomes
      were detected regardless of whether amputation or limb salvage was performed.
      Severity of soft tissue injury was more predictive of outcome than the surgical
      approach used. CONCLUSIONS: Sociodemographics and soft tissue injury severity are
      more important than treatment approach for predicting clinical and functional
      outcomes at 2 years in patients with proximal tibia metaphyseal fractures with
      severe soft tissue injury. LEVEL OF EVIDENCE: Level III, retrospective
      comparative study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 19862586
TI  - How active are patients undergoing total joint arthroplasty?: A systematic
      review.
AB  - BACKGROUND: Qualitative research studies regarding physical activity in patients
      undergoing total joint arthroplasty (TJA) unfortunately are sparse in the current
      literature. QUESTIONS/PURPOSES: To provide a foundation for future
      investigations, we performed a systematic review to identify the different
      instruments used to quantify physical activity in patients undergoing TJA and to
      determine how active these patients really are. METHODS: We systematically
      reviewed the literature on the bibliographic databases Medline, Cochrane Library,
      and EMBASE published until September 2008, focusing on studies assessing total
      physical activity in patients after or undergoing TJA. Results of those studies
      quantifying physical activity using accelerometers and pedometers were combined
      using meta-analytic methods. RESULTS: In the 26 studies included (n = 2460
      patients), motion sensors and recall questionnaires were most commonly used. The
      research aims and goals varied widely among the studies and the results mainly
      were descriptive. Studies quantifying physical activity using pedometers and
      accelerometers suggested a weighted mean of 6721 steps/day (95% confidence
      interval [CI], 5744-7698). Steps per day determined by accelerometers were 2.2
      times the steps measured by pedometers. Metaregression showed that walking
      activity decreased by 90 steps/day (95% CI, -156 to -23) every year of patient
      age. CONCLUSIONS: These results suggest patients undergoing TJA are less active
      than recommended to achieve health-enhancing activity levels (greater than 10,000
      steps/day), but they appear more active than normally assumed in typical wear
      simulations. Future investigations have to evolve more standardization in the
      assessment and reporting of physical activity in TJA patients.

PMID- 19862587
TI  - Incidence of groin pain after metal-on-metal hip resurfacing.
AB  - Metal-on-metal hip resurfacing is offered as an alternative to traditional THA
      for the young and active adult with advanced osteoarthritis. However, patients
      undergoing hip resurfacing may be predisposed to persistent groin pain due to
      insufficient head/neck offset, an uncovered acetabular component, or both. We
      therefore determined the incidence of groin pain after metal-on-metal hip
      resurfacing, its impact on patient function, and possible risk factors
      contributing to groin pain. We evaluated 116 patients with a followup of at least
      12 months after surgery (mean, 26 months; range, 12-61 months). The mean age was
      48.8 years (range, 24.0-66.3 years), with 21 women (18%) and 95 men (82%). All
      patients were evaluated clinically and radiographically and had a Harris hip
      score, WOMAC, UCLA Activity Rating Scale, and the RAND-36 General Health measure;
      they were specifically asked if they experienced groin pain currently or since
      their surgery. Although all patients had functional improvements postoperatively,
      21 of 116 of the patients (18%) reported groin pain; 12 of these (10% of the
      total) stated the pain limited their activities of daily living and 11 (10%)
      required medication for pain. Female patients were at greater risk of having
      groin pain. Of the patients with groin pain, three patients had muscle atrophy
      with a joint effusion on CT; one of these patients had revision surgery for the
      pain. Patients with metal-on-metal resurfacing may have a higher incidence of
      pain than those with conventional THA. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 19862601
TI  - Intolerance to initial orthostasis relates to systolic BP changes in elders.
AB  - OBJECTIVES: To explore the association of early symptoms of orthostatic
      intolerance (OI) with systolic (SBP), diastolic (DBP) and mean arterial (MAP)
      blood pressure changes in a sample of community-dwelling older people undergoing
      an active stand test; and to establish whether SBP and DBP changes have different
      symptomatic correlates during early orthostasis. METHODS: A total of 224
      community-dwelling older subjects (mean age 72.6 years, 68.8% females) were
      included. All had a Mini-Mental State Examination score >or=23 and no risk
      factors for autonomic neuropathy. Subjects were monitored with the Finometer Pro
      device. Variables reflecting blood pressure changes (absolute low: nadir,
      magnitude of drop: delta, and speed of recovery) were extracted for SBP, DBP and
      MAP with the BeatScope software (5-s averages method), and correlated with self
      reported OI during active stand. RESULTS: Of the 224 subjects, 62 (27.7%)
      reported OI. SBP changes had strong bivariate associations with OI, but not DBP
      changes. A logistic regression model suggested that the rate of recovery of SBP
      during the first 30 s following active stand is more important as a determinant
      of OI than SBP nadir or delta. Subjects who recovered at least 80% of their
      baseline SBP within 30 s post-stand were very unlikely to report OI.
      INTERPRETATION: Our study suggests that orthostatic SBP changes may be more
      important than DBP changes as determinants of early OI during active stand. The
      crucial importance of the quick recovery of SBP in order to avoid OI is
      biologically plausible and is discussed in the context of initial OH
      pathophysiology.

PMID- 19862602
TI  - Iron chelation therapy in the management of thalassemia: the Asian perspectives.
AB  - Worldwide, thalassemia is the most commonly inherited hemolytic anemia, and it is
      most prevalent in Asia and the Middle East. Iron overload represents a
      significant problem in patients with transfusion-dependent beta-thalassemia.
      Chelation therapy with deferoxamine has traditionally been the standard
      therapeutic option but its usage is tempered by suboptimal patient compliance due
      to the discomfort and demands associated with the administration regimen.
      Therefore, a great deal of attention has been focused on the development of oral
      chelating agents. Deferiprone, even though available for nearly two decades in
      Asia with recent encouraging data on cardiac iron removal and long-term efficacy,
      has serious adverse effects including agranulocytosis and neutropenia which has
      impeded it from routine clinical practice. A novel oral chelator; deferasirox is
      effective throughout a 24 h dosing period and both preclinical and clinical data
      indicate that it successfully removes both hepatic and cardiac iron. In Asia,
      optimal management of severe thalassemia patients and the availability and access
      to oral iron chelators still presents a major challenge in many countries. In
      this regard, the development and implementation of consensus guidelines for
      management of Asian patients with transfusion-dependent thalassemia will be a
      major step towards improving and maintaining the continuity of patient care.

PMID- 19862603
TI  - Functional effects of protein kinases and peroxynitrite on cardiac carnitine
      palmitoyltransferase-1 in isolated mitochondria.
AB  - We have previously shown that metoprolol can inhibit carnitine
      palmitoyltransferase-1 catalytic activity and decrease its malonyl CoA
      sensitivity within 30 min, suggesting the importance of a covalent modification.
      The aim of this study was to characterize the effects of PTMs on CPT-1 in the
      heart. Mitochondria were isolated from the hearts of male Wistar rats and
      incubated with kinases of interest (protein kinase A, CAMK-II, p38 MAPK, Akt) or
      with peroxynitrite and sodium nitroprusside. PKA decreased CPT-1 malonyl CoA
      sensitivity, associated with phosphorylation of CPT-1A, whereas CAMK-II increased
      malonyl CoA sensitivity by phosphorylating CPT-1B. p38 bound to CPT-1B and
      stimulated CPT-1 activity. The association of CPT-1 with these kinases and their
      scaffolding proteins was confirmed in co-localization studies. Peroxynitrite and
      sodium nitroprusside reversibly stimulated CPT-1 activity, and the change in CPT
      1B activity was most consistently associated with glutathiolation of CPT-1B.
      These studies have identified a new regulatory system of kinases, scaffolding
      proteins and thiol redox chemistry which can control cardiac CPT-1 in vitro.

PMID- 19862604
TI  - Design of a 3D aligned myocardial tissue construct from biodegradable polyesters.
AB  - The heart does not regenerate new functional tissue when myocardium dies
      following coronary artery occlusion, or if it is defective. Ventricular
      restoration involves excising the infarct and replacing it with a cardiac patch
      to restore the heart to a more healthy condition. The goal of this study was to
      design and develop a clinically applicable myocardial patch to replace myocardial
      infarcts and improve long-term heart function. A basic design composed of 3D
      microfibrous mats that house mesenchymal stem cells (MSCs) was developed from
      human umbilical cord matrix (Wharton's Jelly) cells aligned in parallel to each
      other mimicking the native myocardium. Poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) (PHBV), poly(L-D,L-lactic acid) (P(L-D,L)LA) and poly(glycerol
      sebacate) (PGS) were blended and electrospun into aligned fiber mats with fiber
      diameter ranging between 1.10 and 1.25 microm. The micron-sized parallel fibers
      of the polymer blend were effective in cell alignment and cells have penetrated
      deep within the mat through the fiber interstices, occupying the whole structure;
      8-9 cell layers were obtained. Biodegradable macroporous tubings were introduced
      to serve as nutrient delivery route. It was possible to create a thick myocardial
      patch with structure similar to the native tissue and with a capability to grow.

PMID- 19862606
TI  - Rational design of multiple TB antigens TB10.4 and TB10.4-Ag85B as subunit
      vaccine candidates against Mycobacterium tuberculosis.
AB  - PURPOSE: Rational design of recombinant antigens TB10.4 and TB10.4-Ag85B as
      subunit vaccine candidates against Mycobacterium tuberculosis. The main purpose
      is to obtain a large quantity of soluble antigens. METHODS: Recombinant antigens
      were cloned in frame with the N-terminal thioredoxin and expressed in E. coli.
      The thioredoxin tag was removed by TEV protease. Nickel-affinity and size
      exclusion chromatography were used to purify antigens to homogeneity. Antigen
      stability at different pH levels was studied by photon correlation spectrometry.
      Circular dichroism was used to probe antigen secondary structure and thermal
      stability. RESULTS: N-terminal thioredoxin fusion dramatically increased antigen
      solubility. Soluble TB10.4 and TB10.4-Ag85B were purified to homogeneity and
      obtained in milligram quantity. Co-expression of bacteria chaperons increased the
      yield of TB10.4-Ag85B. Soluble TB10.4 and TB10.4-Ag85B purified from the
      inclusion body showed a reversible structure change. However, Ag85B and soluble
      TB10.4-Ag85B showed a clear melting temperature, above which the secondary
      structure was lost dramatically. CONCLUSION: Soluble TB10.4 and TB10.4-Ag85B were
      purified from the E. coli in significant quantities. The methods to purify and
      characterize these recombinant antigens were established, which paved the way for
      further vaccine development based on these antigens.

PMID- 19862607
TI  - PEGylated PAMAM dendrimer-doxorubicin conjugates: in vitro evaluation and in vivo
      tumor accumulation.
AB  - PURPOSE: To investigate the effects of PEGylation degree and drug conjugation
      style on the in vitro and in vivo behavior of PEGylated polyamidoamine (PAMAM)
      dendrimers-based drug delivery system. METHODS: Doxorubicin (DOX) was conjugated
      to differently PEGylated PAMAM dendrimers by acid-sensitive cis-aconityl linkage
      and acid-insensitive succinic linkage to produce the products of PPCD and PPSD
      conjugates, respectively. In vitro evaluations including pH-dependent DOX
      release, cytotoxicity, cellular uptake, cell internalization mechanism, and
      intracellular localization were performed. Tumor accumulation was also visualized
      by in vivo fluorescence imaging. RESULTS: DOX release from PPCD conjugates
      followed an acid-triggered manner and increased with increasing PEGylation
      degree. In vitro cytotoxicity of PPCD conjugates against ovarian cancer (SKOV-3)
      cells increased, while cellular uptake decreased with increasing PEGylation
      degree. PPSD conjugates released negligible drug at any tested pH condition and
      were less cytotoxic. The conjugates were internalized by SKOV-3 cells via
      clathrin-mediated and adsorptive endocytosis, and were delivered to acidic
      lysosomes where DOX was released from PPCD conjugates and diffused into the
      nuclei. PPCD conjugates with highest PEGylation degree showed the highest tumor
      accumulation in mice inoculated with SKOV-3 cells. CONCLUSION: The obtained
      results suggested that PPCD conjugates with highest PEGylation degree would be a
      potential candidate for solid tumor treatment.

PMID- 19862609
TI  - Erythropoiesis stimulating agents in heart failure patients with anemia: a meta
      analysis.
AB  - BACKGROUND: Anemia is prevalent in patients with heart failure and an independent
      prognostic sign of poor outcome. The current report is a meta-analysis of
      published clinical trials assessing the use of erythropoeisis stimulating agents
      (ESA) in heart failure (HF) patients with anemia. METHODS: Literature and Medline
      search was performed to identify studies with control groups (case-control,
      cohort or randomized controlled trials) that examined the effect of ESA therapy
      in patients with HF and anemia. RESULTS: Seven prospective controlled trials met
      inclusion criteria (n = 663 subjects). The ESA studied was darbepoetin in 4
      trials and erythropoietin in 3 trials. Mean follow up period ranged from 12 to 27
      weeks. Compared to placebo ESA therapy was associated with improvement in six
      cardiovascular parameters assessed by at least three of the analyzed trials,
      including increase in hemoglobin levels 2.35(95% confidence interval [Cl], 1.76
      2.93, P < 0.00001), increase in exercise duration 0.91(95% Cl, 0.08-1.73, P =
      0.03), improvement in New York Heart Association functional class -1.46(95% Cl, 
      2.32 to -0.60, P = 0.0009), improvement in 6-minute walk test 1.42(95% Cl, 0.31
      2.54, P = 0.01), decrease in B-type natriuretic peptide -0.54(95% Cl, -1.03 to 
      0.06, P = 0.03), and improvement in peak oxygen consumption 0.93(95% Cl, 0.52
      1.34, P < 0.00001). CONCLUSION: In patients with heart failure and anemia,
      erythropoiesis stimulating agent therapy appears to have a positive effect on
      several important cardiovascular parameters, compared to control therapy. Large
      prospective randomized controlled trials are warranted to comprehensively
      evaluate the potential effects of erythropoiesis stimulating agents on clinical
      outcomes in heart failure patients with anemia.

PMID- 19862610
TI  - A biologically plausible model of time-scale invariant interval timing.
AB  - The temporal durations between events often exert a strong influence over
      behavior. The details of this influence have been extensively characterized in
      behavioral experiments in different animal species. A remarkable feature of the
      data collected in these experiments is that they are often time-scale invariant.
      This means that response measurements obtained under intervals of different
      durations coincide when plotted as functions of relative time. Here we describe a
      biologically plausible model of an interval timing device and show that it is
      consistent with time-scale invariant behavior over a substantial range of
      interval durations. The model consists of a set of bistable units that switch
      from one state to the other at random times. We first use an abstract formulation
      of the model to derive exact expressions for some key quantities and to
      demonstrate time-scale invariance for any range of interval durations. We then
      show how the model could be implemented in the nervous system through a generic
      and biologically plausible mechanism. In particular, we show that any system that
      can display noise-driven transitions from one stable state to another can be used
      to implement the timing device. Our work demonstrates that a biologically
      plausible model can qualitatively account for a large body of data and thus
      provides a link between the biology and behavior of interval timing.

PMID- 19862611
TI  - CuBIC: cumulant based inference of higher-order correlations in massively
      parallel spike trains.
AB  - Recent developments in electrophysiological and optical recording techniques
      enable the simultaneous observation of large numbers of neurons. A meaningful
      interpretation of the resulting multivariate data, however, presents a serious
      challenge. In particular, the estimation of higher-order correlations that
      characterize the cooperative dynamics of groups of neurons is impeded by the
      combinatorial explosion of the parameter space. The resulting requirements with
      respect to sample size and recording time has rendered the detection of
      coordinated neuronal groups exceedingly difficult. Here we describe a novel
      approach to infer higher-order correlations in massively parallel spike trains
      that is less susceptible to these problems. Based on the superimposed activity of
      all recorded neurons, the cumulant-based inference of higher-order correlations
      (CuBIC) presented here exploits the fact that the absence of higher-order
      correlations imposes also strong constraints on correlations of lower order.
      Thus, estimates of only few lower-order cumulant suffice to infer higher-order
      correlations in the population. As a consequence, CuBIC is much better compatible
      with the constraints of in vivo recordings than previous approaches, which is
      shown by a systematic analysis of its parameter dependence.

PMID- 19862612
TI  - LFP spectral peaks in V1 cortex: network resonance and cortico-cortical feedback.
AB  - This paper is about how cortical recurrent interactions in primary visual cortex
      (V1) together with feedback from extrastriate cortex can account for spectral
      peaks in the V1 local field potential (LFP). Recent studies showed that visual
      stimulation enhances the gamma-band (25-90 Hz) of the LFP power spectrum in
      macaque V1. The height and location of the gamma-band peak in the LFP spectrum
      were correlated with visual stimulus size. Extensive spatial summation, possibly
      mediated by feedback connections from extrastriate cortex and long-range
      horizontal connections in V1, must play a crucial role in the size dependence of
      the LFP. To analyze stimulus-effects on the LFP of V1 cortex, we propose a
      network model for the visual cortex that includes two populations of V1 neurons,
      excitatory and inhibitory, and also includes feedback to V1 from extrastriate
      cortex. The neural network model for V1 was a resonant system. The model's
      resonance frequency (ResF) was in the gamma-band and varied up or down in
      frequency depending on cortical feedback. The model's ResF shifted downward with
      stimulus size, as in the real cortex, because increased size recruited more
      activity in extrastriate cortex and V1 thereby causing stronger feedback. The
      model needed to have strong local recurrent inhibition within V1 to obtain ResFs
      that agree with cortical data. Network resonance as a consequence of recurrent
      excitation and inhibition appears to be a likely explanation for gamma-band peaks
      in the LFP power spectrum of the primary visual cortex.

PMID- 19862613
TI  - Identification and characterization of a highly virulent triple reassortant H1N1
      swine influenza virus in the United States.
AB  - A highly virulent H1N1 influenza A virus, A/Swine/Kansas/77778/2007 (KS07), which
      caused approximately 10% mortality in finishing pigs, was isolated from herds in
      the Midwestern United States. Molecular and phylogenic analysis revealed this
      swine isolate was a triple reassortant virus, similar to an H1N1 virus that
      infected humans and pigs at an Ohio county fair in August 2007. A pig challenge
      model was developed to evaluate the pathogenicity and transmission capacity of
      the KS07 virus. The results confirmed that the KS07 virus is highly virulent in
      pigs and easily transmitted to sentinel animals. The KS07 virus failed to cross
      react with a panel of H1-specific swine sera. Interestingly, the KS07 virus shed
      for a prolonged period up to 7 days in infected pigs, indicating that this virus
      can spread efficiently between animals. The highly virulent H1N1 swine influenza
      virus is further evidence of reassortment among avian, human and swine influenza
      viruses and justifies the need for continued surveillance of influenza viruses in
      swine.

PMID- 19862615
TI  - A social ecological approach to investigating relationships between housing and
      adaptive functioning for persons with serious mental illness.
AB  - This paper seeks to advance mental health-housing research regarding which
      factors of housing and neighborhood environments are critical for adaptive
      functioning, health, and recovery for persons with serious mental illness (SMI).
      Housing and neighborhood environments are particularly important for persons with
      SMI because of the prevalence of poor housing conditions among this population.
      Most mental health-housing research has been limited by a focus on problems in
      environments and functioning. The paper seeks to expand the mental health-housing
      research agenda to consider protective factors that promote community integration
      and adaptive functioning. We provide an account of how social ecology theory
      transformed a research program, from examining individual risk factors to
      investigating the functioning of persons in the contexts of their housing and
      neighborhood experiences. The resulting housing environment framework-physical
      aspects of housing and neighborhoods, social environment of neighborhoods, and
      interpersonal relationships tied to housing-allows for identification of
      opportunities for health promotion and facilitation of participation in community
      based settings. This program of research draws upon several methods to understand
      the social experience of persons with SMI living in community settings-survey
      research, qualitative interviews, Geographic Information Systems, participatory
      research, and visual ethnography. In this paper, we present how social ecology
      theory was instrumental in the development of new housing environment measures,
      the selection of appropriate research methods, and framing research questions
      that are building a new empirical base of knowledge about promoting adaptive
      functioning, health, and recovery for persons with SMI living in community
      settings.

PMID- 19862616
TI  - Editorial.

PMID- 19862614
TI  - A review of combined TMS-EEG studies to characterize lasting effects of
      repetitive TMS and assess their usefulness in cognitive and clinical
      neuroscience.
AB  - Transcranial magnetic stimulation (TMS) has developed into a powerful tool for
      studying human brain physiology and brain-behavior relations. When applied in
      sessions of repeated stimulation, TMS can lead to changes in neuronal
      activity/excitability that outlast the stimulation itself. Such aftereffects are
      at the heart of the offline TMS protocols in cognitive neuroscience and
      neurotherapeutics. However, whether these aftereffects are of applied interest
      critically depends on their magnitude and duration, which should fall within an
      experimentally or clinically useful range without increasing risks and adverse
      effects. In this short review, we survey combined TMS-EEG studies to characterize
      the TMS-aftereffects as revealed by EEG to contribute to the characterization of
      the most effective and promising repetitive TMS-parameters. With one session of
      conventional repetitive TMS (of fixed pulse frequency), aftereffects were
      consistently comparable in magnitude to EEG-changes reported after learning or
      with fatigue, and were short-lived (<70 min). The few studies using recently
      developed protocols (such as theta burst stimulation) suggest comparable effect
      size but longer effect-durations. Based on the reviewed data, it is expected that
      TMS-efficacy can be further promoted by repeating TMS-sessions, by using EEG
      gated TMS to tailor TMS to current neuronal state, or by other, non-conventional
      TMS-protocols. Newly emerging developments in offline TMS research for cognitive
      neuroscience and neurotherapeutics are outlined.

PMID- 19862617
TI  - Mathematical modeling of flow-generated forces in an in vitro system of cardiac
      valve development.
AB  - Heart valve defects are the most common cardiac defects. Therefore, defining the
      mechanisms of cardiac valve development is critical to our understanding and
      treatment of these disorders. At early stages of embryonic cardiac development,
      the heart begins as a simple tube that then becomes constricted into separate
      atrial and ventricular regions by the formation of small, mound-like structures,
      called atrioventricular (AV) cushions. As valve development continues, these
      mounds fuse and then elongate into valve leaflets. A longstanding hypothesis
      proposes that blood flow-generated shear stress and pressure are critical in
      shaping the cushions into leaflets. Here we show results from a two-dimensional
      mathematical model that simulates the forces created by blood flow present in a
      developing chick heart and in our in vitro, tubular model system. The model was
      then used to predict flow patterns and the resulting forces in the in vitro
      system. The model indicated that forces associated with shear stress and pressure
      have comparable orders of magnitude and collectively produce a rotational profile
      around the cushion in the direction of flow and leaflet growth. Further, it was
      concluded that the replication of these forces on a cushion implanted in our
      tubular in vitro system is possible. Overall, the two-dimensional, mathematical
      model provides insight into the forces that occur during early cardiac valve
      elongation.

PMID- 19862618
TI  - Here in Vermont. Editorial.

PMID- 19862619
TI  - Extending religion-health research to secular minorities: issues and concerns.
AB  - Claims about religion's beneficial effects on physical and psychological health
      have received substantial attention in popular media, but empirical support for
      these claims is mixed. Many of these claims are tenuous because they fail to
      address basic methodological issues relating to construct validity, sampling
      methods or analytical problems. A more conceptual problem has to do with the near
      universal lack of atheist control samples. While many studies include samples of
      individuals classified as "low spirituality" or religious "nones", these groups
      are heterogeneous and contain only a fraction of members who would be considered
      truly secular. We illustrate the importance of including an atheist control group
      whenever possible in the religiosity/spirituality and health research and discuss
      areas for further investigation.

PMID- 19862620
TI  - Religious support, motives for having large families, and psychological
      functioning among religious Jewish mothers.
AB  - The effects of religious support, maternal motivations for having large families,
      and their interactions on psychological functioning were assessed in a sample of
      79 religious Israeli Jewish mothers of six or more children. Religious support
      from religious leaders, community, and G-d--as well as faith-focused maternal
      motivation--were all positively related to adaptive psychological functioning. In
      contrast, self-focused maternal motivation was negatively related to adaptive
      functioning. Moreover, religious support and maternal motivation were both
      related to psychological functioning even after controlling for social support.
      Finally, several significant interactions between religious support and maternal
      motivation emerged and are also discussed.

PMID- 19862621
TI  - John Nash, game theory, and the schizophrenic brain.
AB  - This article focuses on John Nash, recipient of the Nobel Prize in Economics in
      1994, and subject of the Award winning 2001 film A Beautiful Mind, who was
      diagnosed with paranoid schizophrenia in 1958 at the age of 29. After presenting
      an account of the emergence, course, and eventual remission of his illness, the
      article argues for the relevance of his contribution to game theory, known as the
      Nash equilibrium, for which he received the Nobel Prize, to research studies of
      the schizophrenic brain and how it deviates from the normal brain. The case is
      made that the Nash equilibrium is descriptive of the normal brain, whereas the
      game theory formulated by John van Neumann, which Nash's theory challenges, is
      descriptive of the schizophrenic brain. The fact that Nash and his colleagues in
      mathematics did not make the association between his contributions to mathematics
      and his mental breakdown and that his later recovery exemplified the validity of
      this contribution are noted and discussed. Religious themes in his delusional
      system, including his view of himself as a secret messianic figure and the
      biblical Esau, are interpreted in light of these competing game theories and the
      dysfunctions of the schizophrenic brain. His recognition that his return to
      normalcy came at the price of his sense of being in relation to the cosmos is
      also noted.

PMID- 19862623
TI  - Cogrinding as a tool to produce sustained release behavior for theophylline
      particles containing magnesium stearate.
AB  - The aim of the present study was to explore the cogrinding technique as a tool to
      slow down the drug release from capsule formulations. To this end, the physical
      mixtures of theophylline-magnesium stearate were prepared and subjected to
      different milling times (1, 15, 30, 120 min). In order to investigate the effect
      of magnesium stearate concentration on drug release, various concentrations of
      magnesium stearate (1%, 3%, 5%, and 10%, w/w) were used. The dissolution rate of
      the drug from coground samples and physical mixtures were determined at pH 6.5
      according to USP. The results showed that all coground formulations showed slower
      release rates than their physical mixture counterparts. The effect of cogrinding
      time on the drug release was complex. Cogrinding time had no significant effect
      on drug release when the amount of magnesium stearate was 1% (w/w). When the
      amount of magnesium stearate was increased from 1% to 3% and cogrinding time
      increased from 1 to 5 min, there was a significant reduction in drug release.
      Beyond 5-min cogrinding, the drug release increased again. For coground samples
      containing 5% or 10% (w/w) magnesium stearate, generally, the highest drug
      release was obtained at higher cogrinding time. This was due to a significant
      increase in surface area of particles available for dissolution as proven by
      scanning electron microscopy results. Fourier transform infrared and differential
      scanning calorimetry results ruled out any significant interaction between
      theophylline and magnesium stearate in solid state.

PMID- 19862622
TI  - Improving risk adjustment of self-reported mental health outcomes.
AB  - Risk adjustment for mental health care is important for making meaningful
      comparisons of provider, program, and system performance. The purpose of this
      study was to compare the predictive value of three diagnosis-based risk
      adjustment models for predicting self-reported mental health outcomes. Baseline
      and 3-month follow-up mental health assessments were obtained on 1,023 veterans
      in Veterans Health Administration mental health programs between 2004 and 2006.
      Least-squares regression models predicting mental health outcomes used the
      Behavior and Symptom Identification Scale-24, Veterans RAND-36, and Brief Symptom
      Inventory. Sequential models began with sociodemographics, added baseline self
      reported mental health, and compared three psychiatric case mix schemes: two
      using six diagnostic categories and the other (psychiatric case mix system
      [PsyCMS]) using 46 categories. R (2) were lowest for sociodemographic models
      (0.010-0.074) and highest for models with the PsyCMS (0.187-0.425). The best
      predictive ability was obtained when baseline mental health and 1 year of
      psychiatric diagnoses were added to sociodemographic models; however, the "best"
      risk-adjustment model differed between inpatients and outpatients.

PMID- 19862624
TI  - In vitro characterization and mosquito (Aedes aegypti) repellent activity of
      essential-oils-loaded nanoemulsions.
AB  - The nanoemulsions composed of citronella oil, hairy basil oil, and vetiver oil
      with mean droplet sizes ranging from 150 to 220 nm were prepared and investigated
      both in vitro and in vivo. Larger emulsion droplets (195-220 nm) shifted toward a
      smaller size (150-160 nm) after high-pressure homogenization and resulted in
      higher release rate. We proposed that thin films obtained from the nanoemulsions
      with smaller droplet size would have higher integrity, thus increasing the
      vaporization of essential oils and subsequently prolonging the mosquito repellant
      activity. The release rates were fitted with Avrami's equations and n values were
      in the same range of 0.6 to 1.0, implying that the release of encapsulated
      limonene was controlled by the diffusion mechanism from the emulsion droplet. By
      using high-pressure homogenization together with optimum concentrations of 5%
      (w/w) hairy basil oil, 5% (w/w) vetiver oil (5%), and 10% (w/w) citronella oil
      could improve physical stability and prolong mosquito protection time to 4.7 h
      due to the combination of these three essential oils as well as small droplet
      size of nanoemulsion.

PMID- 19862625
TI  - Ratio spectra derivative and zero-crossing difference spectrophotometric
      determination of olmesartan medoxomil and hydrochlorothiazide in combined
      pharmaceutical dosage form.
AB  - Two simple, economical, rapid, precise, and accurate methods for simultaneous
      determination of olmesartan medoxomil and hydrochlorothiazide in combined tablet
      dosage form have been developed. The first method is based on ratio spectra
      derivative spectrophotometry, and the second method is zero-crossing difference
      spectrophotometry. The amplitudes in the first derivative of the corresponding
      ratio spectra at 231.0 and 271.0 nm were selected to determine olmesartan
      medoxomil and hydrochlorothiazide, respectively. Measurements of absorbance were
      carried out at zero-crossing wavelengths 257.8 and 240.2 nm for olmesartan
      medoxomil and hydrochlorothiazide by zero-crossing difference spectrophotometric
      method. Beer's law is obeyed in the concentration range of 08-24 microg/mL for
      olmesartan medoxomil (OLM) and 05-15 microg/mL for hydrochlorothiazide (HCT) by
      ratio spectra derivative and 05-30 microg/mL for OLM and HCT by zero-crossing
      difference spectrophotometric method. The results of the assay were found to be
      100.46+/-0.95 for OLM and 100.4+/-0.27 for HCT by ratio spectra derivative and
      99.06+/-1.14 for OLM and 100.05+/-0.90 for HCT by zero-crossing difference
      spectrophotometric method. These methods passes F test and t test. Both methods
      were validated statistically and by performing recovery study.

PMID- 19862626
TI  - Kneading technique for preparation of binary solid dispersion of meloxicam with
      poloxamer 188.
AB  - The aim of the present study was to enhance the dissolution rate of meloxicam
      (MLX), a practically water-insoluble drug by preparation of solid dispersion
      using a hydrophilic polymer, poloxamer 188 (PXM). The kneading technique was used
      to prepare solid dispersions. A 3(2) full factorial design approach was used for
      optimization wherein the drug, polymer ratio (X1), and the kneading time (X2)
      were selected as independent variables and the dissolution efficiency at 60 min
      (%DE60) and yield percent were selected as the dependent variable. Multiple
      linear regression analysis revealed that for obtaining higher dissolution of MLX
      from PXM solid dispersions, a high level of X1 and a high level of X2 were
      suitable. The use of a factorial design approach helped in optimization of the
      preparation and formulation of solid dispersion. The optimized formula was
      characterized by solubility studies, angle of repose, and contact angle; Fourier
      transform infrared spectroscopy, differential scanning calorimetry, x-ray
      diffraction studies, and scanning electron microscopy demonstrated that enhanced
      dissolution of MLX from solid dispersion might be due to a decrease in the
      crystallinity of MLX and PXM. Analysis of dissolution data of optimized formula
      indicated the best fitting with Korsemeyer-Peppas model and the drug release
      kinetics as Fickian diffusion. In conclusion, dissolution enhancement of MLX was
      obtained by preparing its solid dispersion with PXM using kneading technique.

PMID- 19862627
TI  - Determination of benzalkonium chloride partition in micelle solutions using
      ultrafiltration method.
AB  - The objectives of this study were to determine the concentrations of free
      benzalkonium chloride (BAC) and apparent partitions coefficients (Km) in micelle
      solutions and to explore its application in formulation development.
      Ultrafiltration (UF) was carried out using 10K Nanosep devices and centrifugation
      at 5,000 rpm for 5 min. The separation of free BAC from micellar solutions was
      also conducted using ultracentrifugation (UC) method for the comparison with UF
      method. Capillary electrophoresis method was used for the identification of
      micelles. Results showed that a UF method was applicable for quantitatively
      evaluating BAC-micelle interaction in micellar solutions. Unlike UF, UC could not
      completely separate free BAC from the micelles. The free BAC concentrations in
      the micelle solutions decreased with increasing surfactant concentrations. Among
      polysorbate 80, cremophor EL, and tyloxapol, BAC had the highest Km in
      polysorbate 80 solutions. The Km was significantly lower in non-buffered aqueous
      solutions than that in citric buffers. Moreover, increasing surfactant
      concentrations led to reducing antimicrobial activity. The UF is a rapid and
      accurate method that minimally alters the micellar equilibrium for the
      determination of free BAC and Km in micellar solutions. In conclusion, free BAC
      concentration, which is a function of surfactant type, surfactant concentration,
      and ion strength of solution, is likely associated with the antimicrobial
      activity.

PMID- 19862628
TI  - Investigating the principles of recrystallization from glyceride melts.
AB  - Different lipids were melted and resolidified as model systems to gain deeper
      insight into the principles of recrystallization processes in lipid-based dosage
      forms. Solid-state characterization was performed on the samples with
      differential scanning calorimetry and X-ray powder diffraction. Several
      recrystallization processes could be identified during storage of the lipid
      layers. Pure triglycerides that generally crystallize to the metastable alpha
      form from the melt followed by a recrystallization process to the stable beta
      form with time showed a chain-length-dependent behavior during storage. With
      increasing chain length, the recrystallization to the stable beta-form was
      decelerated. Partial glycerides exhibited a more complex recrystallization
      behavior due to the fact that these substances are less homogenous. Mixtures of a
      long-chain triglyceride and a partial glyceride showed evidence of some
      interaction between the two components as the partial glyceride hindered the
      recrystallization of the triglyceride to the stable beta-form. In addition, the
      extent of this phenomenon depended on the amount of partial glyceride in the
      mixture. Based on these results, changes in solid dosage forms based on
      glycerides during processing and storage can be better understood.

PMID- 19862629
TI  - In vitro cutaneous application of ISCOMs on human skin enhances delivery of
      hydrophobic model compounds through the stratum corneum.
AB  - This study aimed to investigate the effect of a novel kind of immune-stimulating
      complexes (ISCOMs) on human skin penetration of model compounds in vitro to
      evaluate their potential as a delivery system, ultimately for transcutaneous
      vaccination. Special focus was on elucidating the mechanisms of penetration.
      Preparation of ISCOMs was done by dialysis and subsequent purification in a
      sucrose density gradient. The penetration pathways of acridine-labeled ISCOMs
      were visualized using confocal laser scanning microscopy (CLSM). Transmission
      electron microscopy (TEM) was used to evaluate the ultrastructural changes in the
      skin after application of the ISCOMs with or without hydration. Transcutaneous
      permeation of the model compound, methyl nicotinate, was evaluated in diffusion
      cells. The prepared ISCOMs were 42-52 nm in diameter as evaluated by dynamic
      light scattering with zeta potentials of -33 to -26.1 mV. TEM investigations
      verified the presence of ISCOM structures. Penetration of acridine into skin was
      greatly increased by incorporation into ISCOMs as visualized by CLSM. Permeation
      of methyl nicotinate was enhanced in the presence of ISCOMs. Ultrastructural
      changes of the intercellular space in the stratum corneum after exposure of
      ISCOMs were observed on micrographs, especially for hydrated skin. In conclusion,
      cutaneous application of ISCOMs leads to increased penetration of hydrophobic
      model compounds through human stratum corneum and thus shows potential as a
      transcutaneous delivery system. The increased penetration seems to be reflected
      by a change in the intercellular space between the corneocytes, and the effect is
      most likely caused by the components of the ISCOMs rather than intact ISCOMs.

PMID- 19862631
TI  - Population ageing research: a family of disciplines.
AB  - To study life course trajectories and ageing, scientific expertise is needed
      beyond epidemiology. More specifically, appropriate models of life course require
      a theoretical micro-foundation, need to incorporate multi-level context
      conditions and the interplay between them. It also requires the application of
      additional social scientific research methods that go beyond the application of
      statistical methods based on the multi-stage life table. These research theories
      and methods are available in disciplines like sociology, cultural anthropology,
      psychology, demography and economics. To effectively study healthy ageing of
      populations the individual approach of epidemiology has to be extended with the
      macro-population and socio-cultural approach of (social) demography and the
      institutional and network approaches of sociology.

PMID- 19862630
TI  - Metal contamination of surface soils of industrial city Sialkot, Pakistan: a
      multivariate and GIS approach.
AB  - In this study concentrations of selected metals viz., Ca, Cd, Co, Cr, Cu, Fe, K,
      Mg, Na, Ni, Pb and Zn in surface soils of Sialkot city known worldwide for
      tanneries and pharmaceutical industries were measured to assess the status of
      urban soil pollution and to identify sources of contamination. Hierarchical
      cluster analysis (HACA) indicated concentrations of Mg and Ca related to parent
      rock material, Cd, Co, and Pb with traffic related activities, Cr, Cu, Ni and Zn
      either associated with automobiles activities or industrial pollution and Fe, K
      and Na related with anthropogenic activities or lithogenous materials.
      Correlation analyses and principal component analysis based on factor analysis
      confirmed the results of HACA. Spatial distribution maps exhibited relatively
      higher concentrations of Cd, Co, Cu, Ni, Pb, Cr and Zn along traffic routes in
      the city and streams. The results highlighted concentration of Cd, Ni, Cr, Zn,
      and Pb measured in urban soil exceeded the permissible limit of surface soils and
      advocated an imperative need for detailed baseline investigations of spatial
      distribution of heavy metals and other contaminants for the formulation of
      geochemical database that should be made available to stakeholder involved in
      monitoring, assessment and conservation of soil contamination for future planning
      and management of the Sialkot city.

PMID- 19862632
TI  - Mixed-muscle electrode placement ("jumping" muscles) may produce false-negative
      results when using transcranial motor evoked potentials to detect an isolated
      nerve root injury in a porcine model.
AB  - INTRODUCTION: Placing EMG electrode pairs that span several muscles is sometimes
      used to enhance the efficacy of electromyographic recordings. This technique,
      often referred to as "jumping," has not been studied when using Motor Evoked
      Potentials (TcMEP) for detecting isolated spinal nerve root injury during spine
      surgery. METHODS: TcMEPs were obtained in seven pigs under general anesthesia.
      One pair of recording electrodes was placed entirely within the tibialis anterior
      (TA) muscle; a second pair had one lead in the TA and the other in the
      gastrocnemius muscle (TA-GAS). The dominant root innervating the TA was
      determined using evoked EMG. MEP amplitudes recorded by the TA and TA-GAS
      electrodes were compared before and after suture ligation of this root in 12
      separate experiments. RESULTS: Mean baseline TcMEP amplitude was not
      significantly different for the TA vs. TA-GAS. After root ligation, mean
      amplitude dropped from baseline by 72 +/- 13% in the TA vs. 50 +/- 29% in the TA
      GAS (p < 0.01). All amplitudes decreased by >50% in the TA group; half of the TA
      GAS group had <50% decrease in amplitude. DISCUSSION: Mixed-myotomal recording
      electrodes did not consistently increase baseline TcMEP amplitude. The decrease
      in amplitude after ligation was both smaller and more variable in the "jumped" TA
      GAS electrodes. Thus, this technique may allow someone relying on TcMEP
      monitoring to miss an otherwise detectable isolated nerve root injury (i.e., have
      a false-negative result).

PMID- 19862633
TI  - Association of maternal and intrauterine characteristics with age at menarche in
      a multiethnic population in Hawaii.
AB  - This study seeks to further elucidate the mother-daughter hormonal relationship
      and its effects on daughter's breast cancer risk through the association with
      early age at menarche. Four hundred and thirty-eight healthy girls, age 9-18 and
      of White, Asian, and/or Polynesian race/ethnicity, were recruited from an HMO on
      Oahu, Hawaii. Anthropometric measures were taken at a clinic visit, and family
      background questionnaires were completed. Cox proportional hazards regression was
      used to test the association of maternal and intrauterine hormone-related
      exposures with age at menarche. Weight and gestational age at birth and maternal
      pregnancy-induced nausea were not associated with age at menarche. Each year
      older of the mother's age at menarche was associated with a 21% reduced risk of
      an early age at menarche for the daughter (95% CI: 0.73-0.86). This association
      between mother's and daughter's menarcheal age was statistically significant for
      girls of Asian, White, and Mixed, Asian/White race/ethnicity, but not for girls
      of Mixed, part-Polynesian race/ethnicity (p (interaction) = 0.01). There was a
      suggestion that maternal history of breast cancer was associated with an
      increased risk of early age at menarche (HR = 2.18, 95% CI: 0.95-4.98); there was
      no association with second-degree family history. These findings support the
      hypothesis that maternal and intrauterine hormone-related exposures are
      associated with age at menarche.

PMID- 19862634
TI  - Environmental quality of Korean coasts as determined by modified Shannon-Wiener
      evenness proportion.
AB  - The coast of the Korean peninsula experiences a range of human impacts, including
      pollution, shipping, reclamation, and aquaculture, that have motivated numerous
      local studies of macrobenthic organisms. In this paper, 1,492 subtidal stations
      were compiled from 23 studies (areas) to evaluate environmental quality on a
      broader scale. A common index in biomonitoring, Shannon-Wiener evenness
      proportion (SEP), could not incorporate azoic or single-species samples. This
      shortcoming was overcome by developing an inverse function of SEP (ISEP), which
      was positively correlated with independent measures of water quality available
      for nine sites and was not biased by the size of the sampling unit. Additionally,
      at Shihwa Dike, where samples were collected before and after reinstating a tidal
      connection with the ocean, ISEP values improved over time, as expected. Thus, it
      is now possible to assign Korean subtidal sites to seven ISEP "grades" and to use
      their values and trends to guide coastal management.

PMID- 19862635
TI  - Determining recreational, scenic, and historical-cultural potentials of landscape
      features along a segment of the ancient Silk Road using factor analyzing.
AB  - Generally, roads are structures connecting areas of special importance to each
      other (e.g., from urban areas to villages). In addition to functioning as
      transportation mediums, roads have aesthetic qualities by means of their
      recreational, scenic, and cultural functions. One of these unexplored roads, the
      Trabzon-Gumushane old state highway in the Northeast Turkey, the subject of this
      study, is quite unique for being a part of the historical Silk Road. The aim of
      the study is to determine the recreational, scenic, and cultural potentials of
      this road and to identify the landscape qualities based on these potentials.
      After dividing the road into three sections for comparison purposes, data
      gathered from basic digital maps obtained from The General Directorate of Rural
      Services (the governmental agency that is responsible for producing such digital
      maps) and field trips were entered into maps using geographic information system
      followed by creating demonstration films using photographs and video camera
      images of the natural and cultural characteristics of the area. Then, these films
      were evaluated by an expert team to identify the road's recreational, scenic, and
      cultural potentials. The results of the evaluation process, the relationships
      between determined landscape characteristics for each function, and the
      contribution scores of different functions assigned for the artificial features
      were statistically analyzed. The analyses showed a very strong relationship
      between the sections and the contribution scores of the recreation and the scenic
      functions. The results of these analyses also revealed some landscape
      characteristics having high contribution values for all the functions. This, in
      turn, helped in determining a potential of the study area to become a greenway.

PMID- 19862636
TI  - Two-dimensional finite elements model for selenium transport in saturated and
      unsaturated zones.
AB  - A two-dimensional finite element model was developed to simulate species of
      selenium transport in two dimensions in both saturated and unsaturated soil
      zones. The model considers water, selenate, selenite, and selenomethionine uptake
      by plants. It also considers adsorption and desorption, oxidation and reduction,
      volatilization, and chemical and biological transformations of selenate,
      selenite, and selenomethionine. In addition to simulating water flow, selenate,
      selenite, and selenomethionine transport, the model also simulates organic and
      gaseous selenium transport. The developed model was applied to simulate two
      different observed field data. The simulation of the observed data was
      satisfactory, with mean absolute error of 48.5 microg/l and mean relative error
      of 8.9%.

PMID- 19862637
TI  - High-level expression of Camelid nanobodies in Nicotiana benthamiana.
AB  - Nanobodies (or VHHs) are single-domain antigen-binding fragments derived from
      Camelid heavy chain-only antibodies. Their small size, monomeric behaviour, high
      stability and solubility, and ability to bind epitopes not accessible to
      conventional antibodies make them especially suitable for many therapeutic and
      biotechnological applications. Here we describe high-level expression, in
      Nicotiana benthamiana, of three versions of an anti-hen egg white lysozyme (HEWL)
      nanobody which include the original VHH from an immunized library (cAbLys3), a
      codon-optimized derivative, and a codon-optimized hybrid nanobody comprising the
      CDRs of cAbLys3 grafted onto an alternative 'universal' nanobody framework. His6-
      and StrepII-tagged derivatives of each nanobody were targeted for accumulation in
      the cytoplasm, chloroplast and apoplast using different pre-sequences. When
      targeted to the apoplast, intact functional nanobodies accumulated at an
      exceptionally high level (up to 30% total leaf protein), demonstrating the great
      potential of plants as a nanobody production system.

PMID- 19862638
TI  - Germ-line transmission of lentiviral PGK-EGFP integrants in transgenic cattle:
      new perspectives for experimental embryology.
AB  - Lentiviral vectors are a powerful tool for the genetic modification of livestock
      species. We previously generated transgenic founder cattle with lentiviral
      integrants carrying enhanced green fluorescent protein (EGFP) under the control
      of the phosphoglycerate kinase (PGK) promoter. In this study, we investigated the
      transmission of LV-PGK-EGFP integrants through the female and male germ line in
      cattle. A transgenic founder heifer (#562, Kiki) was subjected to superovulation
      treatment and inseminated with semen from a non-transgenic bull. Embryos were
      recovered and transferred to synchronized recipient heifers, resulting in the
      birth of a healthy male transgenic calf expressing EGFP as detected by in vivo
      imaging. Semen from a transgenic founder bull (#561, Jojo) was used for in vitro
      fertilization (IVF) of in vitro matured (IVM) oocytes from non-transgenic cows.
      The rates of cleavage and development to blastocyst in vitro corresponded to 52.0
      +/- 4.1 and 24.5 +/- 4.4%, respectively. Expression of EGFP was observed at
      blastocyst stage (day 7 after IVF) and was seen in 93.0% (281/302) of the
      embryos. 24 EGFP-expressing embryos were transferred to 9 synchronized
      recipients. Analysis of 2 embryos, flushed from the uterus on day 15, two fetuses
      recovered on day 45, and a healthy male transgenic calf revealed consistent high
      level expression of EGFP in all tissues investigated. Our study shows for the
      first time transmission of lentiviral integrants through the germ line of female
      and male transgenic founder cattle. The pattern of inheritance was consistent
      with Mendelian rules. Importantly, high fidelity expression of EGFP in embryos,
      fetuses, and offspring of founder #561 provides interesting tools for
      developmental studies in cattle, including interactions of gametes, embryos and
      fetuses with their maternal environment.

PMID- 19862639
TI  - Cardiovascular magnetic resonance T2 signal abnormalities in left ventricular
      ballooning syndrome.
AB  - Left ventricular ballooning syndrome (LVBS), also known as Takotsubo
      cardiomyopathy, is characterized by regional left ventricular dysfunction
      associated with severe psychological stress. T2 weighted cardiac magnetic
      resonance (CMR) can identify myocardial edema due to ischemia or other insults. A
      standard clinical CMR scan with double inversion recovery fast spin echo T2
      weighted sequences was performed on consecutive patients with LVBS. T2 signal was
      compared in myocardial segments with normal and impaired function based on
      systolic wall thickening (SWT). Eight LVBS patients were identified, all female,
      with a median age of 61 years and median left ventricular ejection fraction of
      52%. Four patients had apical ballooning and four had mid-wall or basal
      ballooning. In severely dysfunctional segments (those with SWT < 25%), the median
      percentage of high T2 signal was 85 compared with 35 in those with SWT > 25% (P <
      0.001). When the segments were categorized into tertiles based on SWT, the
      percentage of high T2 signal was greatest in segments with the worst function
      (68% vs. 43% vs. 31%, P = 0.005). In the five patients who returned for follow
      up, there was a significant reduction in high T2 signal compared with baseline in
      those segments that were initially severely dysfunctional (85% vs. 35%, P <
      0.001). In conclusion, we describe elevated T2 signal consistent with myocardial
      edema in patients with LVBS. The T2 signal is highest in myocardium with the most
      impaired function and resolves over time.

PMID- 19862641
TI  - Memory reconsolidation for natural language processing.
AB  - We propose a model of memory reconsolidation that can output new sentences with
      additional meaning after refining information from input sentences and
      integrating them with related prior experience. Our model uses available
      technology to first disambiguate the meanings of words and extracts information
      from the sentences into a structure that is an extension to semantic networks.
      Within our long-term memory we introduce an action relationships database
      reminiscent of the way symbols are associated in brain, and propose an adaptive
      mechanism for linking these actions with the different scenarios. The model then
      fills in the implicit context of the input and predicts relevant activities that
      could occur in the context based on a statistical action relationship database.
      The new data both of the more complete scenario and of the statistical
      relationships of the activities are reconsolidated into memory. Experiments show
      that our model improves upon the existing reasoning tool suggested by MIT Media
      lab, known as ConceptNet.

PMID- 19862640
TI  - Determinants of overall quality of life in women over the first year after
      surgery for early stage breast cancer.
AB  - PURPOSE: Scores on quality of life (QOL) domains and facets are probably subject
      to fluctuations across time due to the course of breast cancer treatment.
      Existing QOL studies have been cross-sectional. Therefore, this prospective
      follow-up study examined whether QOL domains (physical health, psychological
      health, social relationships, and environment) and QOL facets contributed
      differentially across time to overall QOL in women with early stage breast
      cancer. METHODS: From the 608 participating women, 225 women had early stage
      breast cancer. Before diagnosis and 1, 3, 6, and 12 months after surgical
      treatment, women with early stage breast cancer were assessed on QOL (WHOQOL
      100). RESULTS: Psychological Health and Social Relationships were the QOL domains
      that contributed to overall QOL most consistently at the various time points.
      Physical Health appeared to be a contributor at all time points except 1 month
      after surgery. Environment contributed to a lesser extent to overall QOL compared
      with Physical Health, Psychological Health, and Social Relationships. Different
      facets contribute to overall QOL-dependent of particular measurement points.
      However, the facets Positive Feelings and Personal Relationships were important
      factors at almost all time points of maintaining a good overall QOL. CONCLUSIONS:
      QOL domains and facets contributed differently to overall QOL at various time
      points across treatment in women with early stage breast cancer.

PMID- 19862643
TI  - Astrocytes regulate the expression of insulin-like growth factor 1 receptor (IGF1
      R) in primary cortical neurons during in vitro senescence.
AB  - The role of insulin-like growth factor 1 (IGF1) pathway as regulator of aging and
      age-related diseases is increasingly recognized. Recent evidence has been
      provided that neuronal IGF1-R increases during aging leading to activation of a
      signaling pathway that causes an increased production of amyloid beta-peptide,
      the principal event in the pathogenesis of Alzheimer's disease. Here, by using
      long-term neuronal cultures as a model of aging, we show that astroglial cells
      are required to upregulate the expression of IGF1-R in neurons during in vitro
      senescence. Moreover, evidence is provided that the cross-talk between astrocytes
      and neurons is independent of cell-to-cell contact, and it is mediated by low
      molecular weight soluble factor(s) released by astrocytes in culture medium.
      These results suggest that astrocytes could play an important role in aging and
      age-related pathological processes.

PMID- 19862642
TI  - Thrombospondin-2 and SPARC/osteonectin are critical regulators of bone
      remodeling.
AB  - Thrombospondin-2 (TSP2) and osteonectin/BM-40/SPARC are matricellular proteins
      that are highly expressed by bone cells. Mice deficient in either of these
      proteins show phenotypic alterations in the skeleton, and these phenotypes are
      most pronounced under conditions of altered bone remodeling. For example, TSP2
      null mice have higher cortical bone volume and are resistant to bone loss
      associated with ovariectomy, whereas SPARC-null mice have decreased trabecular
      bone volume and fail to demonstrate an increase in bone mineral density in
      response to a bone-anabolic parathyroid hormone treatment regimen. In vitro,
      marrow stromal cell (MSC) osteoprogenitors from TSP2-null mice have increased
      proliferation but delayed formation of mineralized matrix. Similarly, in cultures
      of SPARC-null MSCs, osteoblastic differentiation and mineralized matrix formation
      are decreased. Overall, both TSP2 and SPARC positively influence osteoblastic
      differentiation. Intriguingly, both of these matricellular proteins appear to
      impact MSC fate through mechanisms that could involve the Notch signaling system.
      This review provides an overview of the role of TSP2 and SPARC in regulating bone
      structure, function, and remodeling, as determined by both in vitro and in vivo
      studies.

PMID- 19862644
TI  - Acute cerebral hemorrhage normalized plasma renin activity in a patient with
      primary aldosteronism.

PMID- 19862645
TI  - Molecular cloning and functional analysis of the FSH receptor gene promoter from
      the volcano mouse (Neotomodon alstoni alstoni).
AB  - To gain further insights on the genetic divergence and the species-specific
      characteristics of the follicle-stimulating hormone receptor (FSHR), we cloned
      946 bp of the 5'-flanking region of the FSHR gene from the volcano mouse
      (Neotomodon alstoni alstoni), and compared its features with those from other
      mammalian species. The sequence of neotomodon FSHR (nFSHR) gene from the
      translation initiation site to -946 is 74, 71, 64, and 59% homologous to rat,
      mouse (129/J), human, and sheep, respectively. The nFSHR 5'-flanking region
      exhibits new interesting putative cis-regulatory elements including those for the
      SRY transcription factor, which had not been previously related to the FSHR gene.
      The transcriptional regulation properties of nFSHR gene were studied in mouse
      Sertoli (MSC-1) and non-Sertoli (H441) cell lines, and compared with those
      obtained with similar 129/J constructs. All constructs tested were more active in
      H441 than in MSC-1 cells. The low transcription levels detected in MSC-1 cells
      probably reflect the recruitment of Sertoli cells-specific nuclear factors that
      repress transcription of the FSHR gene. In H441 cells, 129/J constructs were more
      active than their neotomodon counterparts, indicating important species-specific
      differences in their transcription pattern. Functional analysis of a series of
      progressive 5'-deletion mutants identified regions involved in positive and
      negative transcriptional regulation as well as the strongest minimal promoter
      spanning 260 bp upstream the translation initiation site. The identification of
      inhibitory nuclear transcription factors, which are apparently expressed in MSC-1
      cells, may contribute to a better understanding of the transcriptional regulation
      of the FSHR gene.

PMID- 19862646
TI  - Inhibition of SOCS-3 in adipocytes of rats with diet-induced obesity increases
      leptin-mediated fatty acid oxidation.
AB  - Rats with diet-induced obesity (DIO) usually experience hyperleptinemia. Thus,
      leptin produced by adipocytes does not deplete adipocyte fat, which implying a
      leptin resistance in adipocytes during overnutrition. Here, we induced
      hyperleptinemia in rats by feeding them a diet consisting of 45% fat. In
      epididymal adipose tissues, the mRNA and protein levels of a putative leptin
      resistant factor, suppressor of cytokine signaling 3 (SOCS-3), were increased.
      The mRNA levels of SOCS-3 in adipocytes differentiated from adipose-derived
      stromal cells (ADSCs) were higher in DIO rats than in rats on a 10% fat diet.
      Using SOCS-3 short hairpin RNA lentivirus interference, we found decreased
      expression of acetyl-CoA carboxylase mRNA (a marker of de novo lipogenesis) and
      increased expression of acetyl-CoA oxidase mRNA (a marker of fat oxidation) in
      SOCS-3-knockdown adipocytes after incubation with 50 nM leptin for 6 h. We
      conclude that the SOCS-3 knockdown may have increased the leptin-mediated in situ
      fatty acid oxidation in the DIO adipocytes, and therefore, SOCS-3 might be an
      excellent target for therapeutic intervention for obesity.

PMID- 19862647
TI  - MDR1 polymorphism role in patients treated with cetuximab and irinotecan in
      irinotecan refractory colorectal cancer.
AB  - The aim of the study was to evaluate the influence of the MDR1 C3435T
      polymorphism on the therapeutic response in 23 patients treated with cetuximab
      plus irinotecan for irinotecan refractory liver metastatic colorectal cancer
      considering their KRAS status. Indeed, irinotecan and its active metabolite (SN
      38) are both substrates of P-glycoprotein (P-gp) encoded by MDR1. Patients
      received cetuximab and irinotecan up to progression. The overall survival was 55%
      at 10 months. Overall, four patients had an undetermined KRAS status and two
      patients with mutated KRAS were in progression disease. The response to treatment
      was observed after 3 months among the 17 wild-type KRAS patients. Two patients
      presented a progressive disease (1 TT and 1 CT), eight patients had a stable
      disease (5 CC and 3CT) and five patients had a partial response (3 CC and 2 CT).
      Importantly, 2 patients (2 TT) were in complete response and still alive 5 years
      after starting the treatment, which suggests that the combination of wild-type
      KRAS and MDR1 3435 TT may be a factor of good prognosis. These results suggest
      that EGFR inhibition by cetuximab may overcome this irinotecan resistance by
      abrogating drug efflux depending on MDR1 3435 polymorphism. Among patients
      resistant to irinotecan, it is still possible to use the association of cetuximab
      plus irinotecan to obtain a complete resection of hepatic metastases that is
      necessary to improve their survival.

PMID- 19862650
TI  - [Cardiac pathologies incidentally detected with non-gated chest CT].
AB  - Cardiac imaging using electrocardiogram-gated multi-detector computed tomography
      (MDCT) permits noninvasive diagnosis of congenital and acquired cardiac
      pathologies and has thus become increasingly important in the last years. Several
      studies investigated the incidence and relevance of incidental extracardiac
      structures within the lungs, mediastinum, chest wall, and abdomen with gated
      coronary CT. This resulted in the general acceptance of the review of
      extracardiac structures as a routine component of coronary CT interpretation. On
      the other hand radiologists tend to neglect pericardial and cardiac pathologies
      in non-gated chest CT, which is primarily performed for the evaluation of the
      respiratory system or for tumor staging. Since the introduction of multi-detector
      spiral CT technology, the incidental detection of cardiac and pericardial
      findings has become possible using non-gated chest CT. This article reviews the
      imaging appearances and differential diagnostic considerations of incidental
      cardiac entities that may be encountered in non-gated chest CT.

PMID- 19862651
TI  - In vivo imaging of MSCT and micro-CT: a comparison.
AB  - PURPOSE: To evaluate the potential of MSCT and a novel AmicroCT system to assess
      the volume of malignant brain tumors in rats compared to histology. MATERIALS AND
      METHODS: Fourteen rats underwent stereotactic implantation of GFP-marked F 98
      glioma cells. On day 10 after implantation, animals received double-dose contrast
      enhanced AmicroCT and MSCT imaging using Iomeprol. MSCT- and AmicroCT-derived
      tumor volumes were calculated and compared to histology (fluorescence staining)
      as the gold standard. RESULTS: There was good correlation between the AmicroCT
      derived tumor volume (69 A+ or - 23 mm(3)) and histology (81 A + or - 14 mm(3); p
      > 0.14). MSCT, however, showed significantly smaller tumor volumes (55 A + or -
      25 mm(3)) compared to histology (p < 0.01) but was able to detect the tumors in
      all animals. CONCLUSION: AmicroCT allows in vivo imaging of the contrast
      enhancing parts of experimental gliomas with high correlation to histology.
      Although MSCT is less suitable for assessing exact tumor volume, this method
      reliably detects tumors in rats. Due to the high spatial resolution, AmicroCT
      systems could play an important role for fusion imaging, e. g. to assess
      experimental brain gliomas with multimodal AmicroCT/PET- or AmicroCT/MRI-fusion
      images.

PMID- 19862652
TI  - [Dual energy CT--a new perspective in the diagnosis of gout].
AB  - PURPOSE: To describe the first experience with dual energy CT (DECT) for the
      diagnosis of gout and to evaluate its potential for the clinical routine.
      MATERIALS AND METHODS: DECT examinations acquired with a dual source CT of 71
      regions from 41 patients were evaluated with respect to image quality, amount of
      urate deposits and their location. The amount of urate deposits was described
      using a 4-stage scale: none (1), minimal punctual (up to 2 mm) (2), at least
      moderate (bigger than 2 mm) (3), soft tissue or osseus tophi (4). The DECT
      results were compared with the findings of the diagnostic tools currently in use.
      RESULTS: The DECTs of peripheral regions showed excellent image quality, while
      the image quality was poor in the regions of the trunk. Patients (n) and regions
      (r) with a score of 3 (n = 23, r = 44), 4 (n = 5, r = 8) and 1 (n = 2, r = 2)
      showed a highly significant correlation (p < 0.01) with the currently available
      diagnostic tools. In patients or regions with a score of 2 (n = 7, r = 11), the
      urate deposits were asymptomatic, the serum urate levels were partly elevated (43
      %) and partly normal (57 %). The symptoms were ultimately able to be associated
      with a differential diagnosis. The urate deposits were found in tendons (57),
      articular synovia (25), cartilage (17), soft tissue tophi (8), osseus tophi (5),
      cruciate ligaments (7) and menisci (7). CONCLUSION: DECT allows specific and
      quantitative visualization of urate deposits in peripheral regions. Taking into
      account the amount of urate deposits shown in DECT, the diagnosis of gout can be
      stated reliably. Based on our experience and results, DECT greatly benefits the
      routine diagnosis of gout in peripheral regions.

PMID- 19862653
TI  - [Assessment of pedicle screws following dorsal instrumentation of the spine: a
      comparison of conventional radiographs with multidetector CT].
AB  - PURPOSE: To evaluate the performance of conventional radiographs (CR) for the
      assessment of pedicle screws in comparison with CT including MPR. MATERIALS AND
      METHODS: Comparison of CR and CT for the evaluation of screw length,
      extracorporal perforation (grade A: 0 - 2 mm, B: 3 - 4 mm, C: 5 - 6 mm, D: > 6
      mm, relevant: grade C and D), screw contact/loosening, and subjective image
      quality (1: excellent to 4: non-diagnostic). The sensitivity (SE), specificity
      (SP), positive (PPV) and negative predictive value (NPV), and overall accuracy
      (OA) were calculated with 4x4 contingency tables. The subjective image quality
      was evaluated using the Wilcoxon test (p < 0.05). RESULTS: 411 screws were
      evaluated. The relevant medial perforation was diagnosed with CR/CT in 53(13 %)/
      11(3 %) screws, while the relevant lateral perforation was found in 3(1 %)/ 43(11
      %) screws. Pedicle screw contact was diagnosed by CR/CT in 10(2 %)/ 18(4 %) cases
      and incorrect length was confirmed in 80(20 %)/ 90(22 %) screws. A diagnosis of
      loosening was established in 10(2 %) screws by CR and in 7(2 %) screws by MDCT.
      In summary, CR demonstrated SE, SP, PPV, NPV, and OA for the following variables:
      relevant medial perforation = 64 / 89 / 13 / 99 / 88 %, relevant lateral
      perforation = 4 / 99 / 67 / 90 / 90 %, screw contact = 11 / 98 / 20 / 96 / 94 %,
      incorrect screw length = 86 / 58 / 89 / 51 / 81 %, and screw loosening = 71 %/ 99
      %/ 50 %/ 100 %/ 98 %. The subjective image quality of CR was significantly lower
      compared to CT (2.19 A + or - 0.84 and 1.11 A + or - 0.31; p < 0.001).
      CONCLUSION: CR evaluation of pedicle screws following dorsal instrumentation of
      the spine demonstrated an OA < or = 90 % for relevant medial and lateral
      perforation and for incorrect screw length compared to CT. Thus, reliable
      evaluation of pedicle screws based solely on CR does not seem feasible.

PMID- 19862654
TI  - Can color-coded parametric maps improve dynamic enhancement pattern analysis in
      MR mammography?
AB  - PURPOSE: Post-contrast enhancement characteristics (PEC) are a major criterion
      for differential diagnosis in MR mammography (MRM). Manual placement of regions
      of interest (ROIs) to obtain time/signal intensity curves (TSIC) is the standard
      approach to assess dynamic enhancement data. Computers can automatically
      calculate the TSIC in every lesion voxel and combine this data to form one color
      coded parametric map (CCPM). Thus, the TSIC of the whole lesion can be assessed.
      This investigation was conducted to compare the diagnostic accuracy (DA) of CCPM
      with TSIC for the assessment of PEC. MATERIALS AND METHODS: 329 consecutive
      patients with 469 histologically verified lesions were examined. MRM was
      performed according to a standard protocol (1.5 T, 0.1 mmol/kgbw Gd-DTPA). ROIs
      were drawn manually within any lesion to calculate the TSIC. CCPMs were created
      in all patients using dedicated software (CAD Sciences). Both methods were rated
      by 2 observers in consensus on an ordinal scale. Receiver operating
      characteristics (ROC) analysis was used to compare both methods. RESULTS: The
      area under the curve (AUC) was significantly (p=0.026) higher for CCPM (0.829)
      than TSIC (0.749). The sensitivity was 88.5% (CCPM) vs. 82.8% (TSIC), whereas
      equal specificity levels were found (CCPM: 63.7%, TSIC: 63.0%). CONCLUSION: The
      color-coded parametric maps (CCPMs) showed a significantly higher DA compared to
      TSIC, in particular the sensitivity could be increased. Therefore, the CCPM
      method is a feasible approach to assessing dynamic data in MRM and condenses
      several imaging series into one parametric map.

PMID- 19862655
TI  - Differentiation of parotid gland tumors with contrast-enhanced ultrasound.
AB  - PURPOSE: Pilot study to evaluate a new ultrasound (US) technique for
      differentiating parotid cystadenolymphoma (CL) from pleomorphic adenoma (PA).
      MATERIALS AND METHODS: 27 patients presenting with a palpable lesion of the
      parotid gland were examined by B-mode US. All patients underwent US examination
      with administration of 2.4 ml US contrast medium (USCM). The intratumoral time-to
      peak was determined. The contrast medium inflow curves from the tumor and parotid
      parenchyma were compared by using AUC analysis and compared with histology.
      RESULTS: Histology demonstrated cystadenolymphoma in 9 cases (CL group) and
      pleomorphic adenoma in 9 (PA group). The intratumoral time-to-peak in the PA
      group was markedly longer than in the CL group (26.8 +/- 11.1 sec versus 22.6 +/-
      5.1 sec, p < 0.05). AUC analysis for the tumor area demonstrated a significant
      difference between the PA group (30.3 +/- 24.3 dB/area) and the CL group (77.4 +/
      45.6 dB/area, p < 0.05). CONCLUSION: The standardized analysis of USCM inflow
      curves has the potential to differentiate cystadenolymphoma and pleomorphic
      adenoma. More patient numbers, perhaps with blinded readers, would allow reliable
      diagnostic determination for future studies.

PMID- 19862656
TI  - [Updated German S3-guideline regarding the diagnosis of Crohn's disease-
      implementation of radiological modalities].
AB  - The recently updated German S 3-guideline regarding the diagnosis and treatment
      of Crohn's disease incorporates several changes concerning the radiological
      approach compared to the former guideline. This article focuses on guideline
      based radiological imaging techniques for patients with Crohn's disease. The new
      guideline is also compared to former European and German guidelines in the
      context of recently published radiological literature.

PMID- 19862657
TI  - Development of a permanently controllable rotating biopsy device, Part I:
      theoretical considerations and in-vitro results for five different prototypes.
AB  - PURPOSE: To develop different prototypes of permanently controllable rotating
      biopsy devices with determination of the most efficient prototype in biopsies in
      bovine myocardium. MATERIALS AND METHODS: Five different prototypes of 18-gauge
      rotating biopsy devices were designed and constructed, four (1 - 4) with various
      drill-like cutting edges and one (5) cannula type with a lancet-like helically
      bent cutting edge. Using bovine myocardium as the biopsy tissue, n = 100
      specimens per prototype were obtained, and a quantitative analysis including
      tissue fragmentation, length in mm and weight in mg was carried out. For
      statistical analysis, the chi-square test for tissue fragmentation and Kruskal
      Wallis test for the parameters length and weight were calculated. RESULTS:
      Prototype 5 showed the highest rate of extraction of one-fragment specimens in n
      = 66 cases and the lowest rate of failure to obtain tissue in n = 11 cases. The
      mean length/weight were 4.15 mm/ 3.91 mg for prototype 1, 1.80 mm/ 1.66 mg for
      prototype 2, 4.61 mm/ 3.28 mg for prototype 3, 5.20 mm/ 3.74 mg for prototype 4,
      and 9.57 mm/ 6.97 mg for prototype 5. In all three categories, prototype 5 was
      significantly superior to the prototypes 1 - 4 with p < 0.001. CONCLUSION: The
      cannula type with a lancet-like helically bent cutting edge proved to be the most
      efficient prototype and may now be tested competitively against established
      automated biopsy devices in vitro.

PMID- 19862658
TI  - [Effects of MRI-assayed microvascular permeability on the accumulation of
      vinorelbine in xenograft tumors].
AB  - PURPOSE: To determine the effects of MRI-assayed vascular leakiness on the
      delivery of macromolecular therapeutics to tumors. MATERIALS AND METHODS: MDA-MB
      435 tumors, subcutaneously implanted into nude rats were treated with a single
      dose of bevacizumab at levels of 0.1 mg (n = 5) or 1.0 mg (n = 10) or received
      saline (control animals, n = 8). After 24 hours, albumin-(Gd-DTPA) (30)-enhanced
      MRI was performed. Just prior to MRI, the cytotoxic drug vinorelbine was
      administered intravenously. Upon completion of the MR experiment, tumor
      vinorelbine concentrations were quantified by high performance liquid
      chromatography (HPLC). Vascular leakiness (K (PS)) was calculated based on the
      MRI data using a pharmacokinetic model. RESULTS: K (PS) was calculated as 3.70 +/
      1.12 (control tumors), 1.95 +/- 0.70 (0.1 mg group) and 0.75 +/- 0.46 microl min
      (-1)cm (-3) (1.0 mg group). K (PS) was significantly higher in the control group
      compared to the 1.0 mg bevacizumab group. Vinorelbine concentrations were
      measured as 409.4 +/- 109.7 (control tumors), 387.5 +/- 47.5 (0.1 mg group) and
      250.7 +/- 71.9 (1.0 mg group). These differences were not significant. A moderate
      and significant correlation was found between K (PS) and Vinorelbine
      concentrations in tumors (r = 0.49, p < 0.05). CONCLUSION: MRI-assayed K (PS)
      based on dynamic MRI enhanced by albumin-(Gd-DTPA) (30) correlated significantly
      with vinorelbine accumulation in experimental xenograft tumors under angiogenesis
      inhibition. Thus, the MRI technique applied in our study could potentially help
      to predict accumulation of macromolecular cytotoxic drugs and to optimize
      individual therapeutic regimes in tumors.

PMID- 19862659
TI  - [Occult cervical dysraphism with tethered cord syndrome].

PMID- 19862660
TI  - [Reversible encephalopathy syndrome, RES or PRES: a case with more W (watershed)
      than P (posterior)!].

PMID- 19862661
TI  - [A rare form of cerebral vasculitis: amyloid beta peptide associated angiitis].

PMID- 19862662
TI  - [Isolated sarcoidosis of the spleen and liver as incidental ultrasound finding].

PMID- 19862663
TI  - [A rare differential diagnosis of an apparent pericardial space occupying lesion
      in cardiac MRI: Castleman disease].

PMID- 19862664
TI  - [Stress fracture of the distal leg in advanced age].

PMID- 19862665
TI  - COUP-TFII is regulated by high glucose in endothelial cells.
AB  - Diabetes mellitus is an important risk factor for cardiovascular diseases.
      Clinical evidence supports a link between hyperglycemia, endothelial dysfunction,
      and vascular disorders. However, the precise molecular mechanisms causing
      endothelial dysfunction in diabetic patients remain unclear. An interesting novel
      mediator could be chicken ovalbumin upstream promoter-transcription factor II
      (COUP-TFII), which plays an essential role in glucose metabolism. COUP-TFII is
      known to be expressed in venous endothelial cells. In this study, we show COUP
      TFII expression in human umbilical vein endothelial cells (HUVECs) and human
      coronary artery endothelial cells. HUVECs express glucose transporters 1, 3, 6,
      and 10, and the insulin receptor. Insulin in combination with glucose activates
      protein kinase B (PKB or Akt) phosphorylation via phosphoinositide 3-kinase (PI3
      kinase). Short-term (60-240 min) stimulation of HUVECs with high glucose
      increased COUP-TFII expression independent of insulin. Long-term (48 h)
      stimulation of HUVECs with high glucose augmented expression of the insulin
      receptor and E-selectin, but downregulated COUP-TFII protein expression.
      Downregulation of COUP-TFII by shRNA leads to downregulation of E-selectin and
      upregulation of eNOS and glucose transporters. Our data suggest that COUP-TFII is
      regulated by glucose in a time- and dose-dependent manner in endothelial cells.
      COUP-TFII might affect endothelial function in a diabetic background.

PMID- 19862666
TI  - Expression and function of endocannabinoid receptors in the human adrenal cortex.
AB  - Endogenous cannabinoids are important signaling molecules in neuroendocrine
      control of homeostatic and reproductive functions including stress response and
      energy metabolism. The hypothalamic paraventricular and supraoptic nuclei have
      been shown to release endocannabinoids, which act as retrograde messengers to
      modulate the synaptic release of glutamate during stress response. This study
      endeavors to elucidate possible interaction of the endocannabinoid system with
      the regulation of adrenocortical function at the adrenal level. Human
      adrenocortical NCI-H295R cells and normal human adrenal glands were used to study
      the possible effects of anandamide and cannabinoid receptor 1 (CB1) antagonist
      SR141716A on aldosterone and cortisol secretion. Our data indicate the expression
      of CB1 in human adrenal cortex and adrenocortical NCI-H295R cells; CB2 was not
      expressed. Furthermore, anandamide inhibited basal release and stimulated release
      of adrenocortical steroids (corticosterone and aldosterone); this effect was
      reversed by CB1 antagonist (SR141716A). Therefore, the endocannabinoid system at
      the level of the adrenal, can directly influence adrenocortical steroidogenesis.

PMID- 19862667
TI  - Long-term Safety and Tolerability of Colesevelam HCl in Subjects with Type 2
      Diabetes.
AB  - The bile acid sequestrant, colesevelam hydrochloride, is approved for glycemic
      control in adults with type 2 diabetes. In three double-masked, placebo
      controlled studies, colesevelam hydrochloride 3.75 g/day demonstrated its
      glycemic-lowering properties when added to existing metformin-, insulin-, or
      sulfonylurea-based therapy in adults with inadequately controlled type 2
      diabetes. This was a 52-week open-label extension study conducted at 63 sites in
      the United States and one site in Mexico to further evaluate the safety and
      tolerability of colesevelam hydrochloride in subjects with type 2 diabetes. All
      subjects who completed the three double-masked, placebo-controlled studies were
      eligible to enroll in this open-label extension. In total, 509 subjects enrolled
      and received open-label colesevelam hydrochloride 3.75 g/day for 52 weeks. Safety
      and tolerability of colesevelam hydrochloride was evaluated by the incidence and
      severity of adverse events. In total, 360 subjects (70.7%) completed the
      extension. Of the safety population, 361 subjects (70.9%) experienced an adverse
      event, most (88.1%) being mild or moderate in severity. Fifty-six adverse events
      (11.0%) were drug-related; the most frequent drug-related adverse events were
      constipation and dyspepsia. Thirty-five subjects (6.9%) discontinued due to an
      adverse event. Fifty-four subjects (10.6%) experienced a serious adverse event;
      only one was considered drug-related (diverticulitis). Seventeen subjects (3.3%)
      experienced hypoglycemia; most episodes were mild or moderate in severity.
      Glycemic improvements with colesevelam hydrochloride were seen without change in
      weight over 52 weeks (0.2 kg mean reduction from baseline). Colesevelam
      hydrochloride was safe and well-tolerated as long-term therapy for patients with
      type 2 diabetes.

PMID- 19862668
TI  - Testosterone administration induces protection against global myocardial
      ischemia.
AB  - We tested the hypothesis that chronic testosterone treatment would promote a
      cardioprotective phenotype against ischemia/reperfusion (I/R) injury. For this
      study, 3-month-old F344 male rats underwent sham-surgery, orchiectomy (ORX), or
      ORX plus 21 days testosterone treatment (1.0 mg testosterone/day). At sacrifice,
      cardiac performance was assessed in a working heart model of I/R (25 min of
      global ischemia and 45 min of reperfusion). ORX reduced serum testosterone by
      approximately 98% and testosterone administration elevated serum testosterone to
      a concentration of 4.6-fold over that of Sham-operated controls (p<0.05). ORX did
      not significantly impair recovery of cardiac performance following I/R, but did
      increase cardiac release of lactate dehydrogenase (LDH) during pre- and post
      ischemia (p<0.05). Testosterone administration prevented the ORX-induced increase
      in LDH during both pre- and post-ischemia and increased post-ischemic recovery of
      aortic flow, cardiac output, cardiac work, left ventricular developed pressure,
      and contractility (p<0.05) during reperfusion. Testosterone administration also
      increased left ventricular expression of catalase, but did not affect the
      expression of manganese superoxide dismutase, glutathione peroxidase, or
      sarcolemmal K (ATP) channel protein Kir6.2. Neither circulating nor cardiac
      concentrations of estradiol were altered by either treatment. We conclude that
      administration of high-dose testosterone confers cardioprotection through yet to
      be identified androgen-dependent mechanism(s).

PMID- 19862669
TI  - HPTLC densitometric evaluation of tissue culture extracts of Nothapodytes foetida
      compared to conventional extracts for camptothecin content and antimicrobial
      activity.
AB  - Tissue culture technique is becoming popular because of its well-known ability to
      enhance the content of secondary metabolites in plants. Callus tissue cultures of
      Nothapodytes foetida were developed using 250 different medium compositions to
      optimize this procedure. Methanolic extracts of callus (MEC) and of various parts
      of N. foetida were comparatively analyzed for camptothecin content, and a high
      performance thin layer chromatography method was developed for its quantitation.
      Chloroform-ethylacetate-methanol (4 : 5 : 0.5 v/v) was used as the mobile phase.
      The method was validated for linearity, precision (interday and intraday),
      repeatability, limit of detection (LOD), limit of quantitation (LOQ), and
      accuracy. The relationship between the concentration of standard solutions and
      the peak response was linear within the range of 80 to 480 ng/spot with a
      correlation coefficient of 0.998 +/- 0.020. Instrumental precision was evaluated
      as 0.54 (% CV). Repeatability of sample and standard were estimated to be 1.08
      and 1.01 (% CV), and LOD and LOQ were found to be 40 and 80 ng/spot,
      respectively. The accuracy of the method was checked out by a recovery study and
      the average percentage recovery was calculated as being 99.13 %. The methanolic
      extract of callus grown in tissue culture with medium composition picloram +
      thidiazuron + gibberellic acid (1 : 1 : 4; MEC-PTG) showed a higher percentage of
      camptothecin (5.74 % w/v) than the methanolic extract of fruits (3.56 % w/w),
      leaves (1.56 % w/w), stem (1.19 % w/w), and root (1.11 % w/w). The results of the
      antimicrobial screening indicate that MEC-PTG exhibited maximum activity against
      all microorganisms. Among the fungi tested, MEC-PTG showed maximum activity
      against A. niger and C. albicans (MIC value 10 microg/mL) whereas among bacteria
      strains, its activity was highest against B. subtilis and S. lutea (MIC 20
      microg/mL).

PMID- 19862671
TI  - [Digital radiography in chest imaging of occupational and environmental lung
      diseases].
AB  - The classification of pneumoconiosis according to ILO standard - comparing a X
      ray of the lung with ILO radiographs - is well established in Germany. The
      extension of digital imaging is a challenging task in occupational medicine as
      well as in pneumology. Technical requirements are not known sufficiently and the
      necessary equipment is not well distributed. This paper describes the current
      position on recording, assessment and documentation of digital imaging of the
      lung and pleura.

PMID- 19862670
TI  - Standardization and in vivo antioxidant activity of ethanol extracts of fruit and
      leaf of Piper sarmentosum.
AB  - The present study aimed to investigate standardized ethanol extracts of fruit and
      leaves of Piper sarmentosum for their in vivo antioxidant activity in rats using
      a CCl (4)-induced oxidative stress model. The standardization was based on the
      quantification of the markers pellitorine, sarmentine and sarmentosine by high
      performance liquid chromatography (HPLC), and determination of total primary and
      secondary metabolites. The rats, divided into 7 groups each (n = 6), were used as
      follows: group 1 (CCl (4), negative control), group 2 (untreated, control),
      groups 3 and 4 (fruit extract 250 and 500 mg/kg, respectively), groups 5 and 6
      (leaf extract 250 and 500 mg/kg, respectively) and group 7 (vitamin-E 100 mg/kg,
      positive control). The doses were administered orally for 14 days; 4 h following
      the last dose, a single dose of CCl (4) (1.5 mg/kg) was given orally to all the
      groups except group 2, and after 24 h, blood and liver of each animal were
      obtained. Analysis of plasma and liver homogenate exhibited significant
      preservation of markers of antioxidant activity, total plasma antioxidant
      activity (TPAA), total protein (TP), superoxide dismutase (SOD), catalase (CAT),
      and thiobarbituric acid reactive species (TBARS), in the pretreated groups as
      compared to the CCl (4) group (p < 0.05). Histology of the liver also evidenced
      the protection of hepatocytes against CCl (4) metabolites in the pretreated
      groups. The results of this study indicate the IN VIVO antioxidant activity of
      both extracts of the plant, which may be valuable to combat diseases involving
      free radicals.

PMID- 19862672
TI  - [Official procedural key (OPS 2010)--key to ultrasound diagnosis].

PMID- 19862673
TI  - Cine phase-contrast MRI evaluation of normal aqueductal cerebrospinal fluid flow
      according to sex and age.
AB  - PURPOSE: The aim of this study was cerebrospinal flow quantification in the
      cerebral aqueduct using cine phase-contrast magnetic resonance imaging (MRI)
      technique in both sexes and five different age groups to provide normative data.
      MATERIALS AND METHODS: Sixty subjects with no cerebral pathology were included in
      this study. Subjects were divided into five age groups: < or =14 years, 15-24
      years, 25-34 years, 35-44 years, and > or =45 years. Phase, rephase, and
      magnitude images were acquired by 1.5 T MR unit at the level of cerebral aqueduct
      with spoiled gradient echo through-plane, which is a cine phase-contrast
      sequence. At this level, peak flow velocity (cm/s), average flow rate (cm/ s),
      average flow (L/min), volumes in cranial and caudal directions (mL), and net
      volumes (mL) were studied. RESULTS: There was a statistically significant
      difference in peak flow between the age group of < or =14 years and the older age
      groups. There were no statistically significant differences in average velocity,
      cranial and caudal volume, net volume, and average flow parameters among
      different age groups. Statistically significant differences were not detected in
      flow parameters between sexes. CONCLUSION: When using cine-phase contrast MRI in
      the cerebral aqueduct, only the peak velocity showed a statistically significant
      difference between age groups; it was higher in subjects aged < or =14 years than
      those in older age groups. When performing age-dependent clinical studies
      including adolescents, this should be taken into consideration.

PMID- 19862674
TI  - Posttraumatic labyrinthitis ossificans with perilymphatic fistulization.
AB  - Labyrinthitis ossificans is fibrosis or ossification of the membranous labyrinth.
      Tympanogenic, meningogenic, and hematogenous etiologies are more common than
      trauma in the development of labyrinthitis ossificans. We present a case
      complaining of right-sided hearing loss and symptoms of otitis media and
      positional vertigo resulting from perilymphatic fistulization. Imaging revealed
      labyrinthitis ossificans secondary to temporal bone fracture crossing through the
      otic capsule.

PMID- 19862675
TI  - An unusual case of neurobrucellosis presenting with unilateral abducens nerve
      palsy: clinical and MRI findings.
AB  - Brucellosis is an endemic zoonotic disease in which neurobrucellosis occurs in 5
      10% of cases. Variable clinical and radiological manifestations of
      neurobrucellosis can mimic those of other diseases. In this report, we present
      unusual clinical and magnetic resonance imaging (MRI) findings in a patient with
      neurobrucellosis and unilateral abducens nerve palsy. Her MRI showed punctate
      leptomeningeal enhancement of the cerebellum on contrast-enhanced T1-weighted
      images, and a focal area of hyperintensity in the splenium of the corpus callosum
      on T2-weighted images.

PMID- 19862676
TI  - Atypical mycobacterial tenosynovitis and bursitis of the wrist.
AB  - Atypical mycobacterial tenosynovitis of the wrist can easily be misdiagnosed as
      synovial chondromatosis. Both sonography and magnetic resonance imaging plays an
      important role in depicting "rice bodies" within the distended tendon sheaths and
      bursae of atypical mycobacterial infection. An endemic place for Mycobacterium
      species and the occupation of the patient should raise the suspicion for the
      disease. Polymerase chain reaction of the distended tendon fluid is a sensitive,
      specific and rapid method in identification of the mycobacteria.

PMID- 19862677
TI  - Iliac vascular complication after spinal surgery: immediate endovascular repair
      following CT angiographic diagnosis.
AB  - Iliac arterial injuries are rare but important complications that can develop
      after spinal surgery. The presentation of these injuries is usually late, with
      symptoms such as leg swelling or cardiac failure. However, acute massive bleeding
      may be a sign of early presentation as in our patient. Herein, we present a case
      of life-threatening bleeding with early computed tomography angiographic
      diagnosis of common iliac artery pseudoaneurysm and iliac arteriovenous fistula
      secondary to spinal surgery which was successfully managed by endovascular stent
      graft treatment.

PMID- 19862678
TI  - HIV-infected hemophilia a patient presenting with gynecomastia.
AB  - We describe the case of a 24-year-old hemophilic man who had been a human
      immunodeficiency virus (HIV)-positive for the past 22 years and presented to our
      hospital with bilateral breast enlargement with the presence of
      microcalcifications. Etiology of breast enlargement in male HIV population and
      differential diagnosis between true gynecomastia and lipomastia are also
      discussed.

PMID- 19862679
TI  - Degassing-assisted patterning of cell culture surfaces.
AB  - We developed an alternative patterning technique which is capable of producing
      both topographic and biochemical features for cell culture studies. This
      technique is based on microaspiration induced with a degassed poly
      (dimethylsiloxane) (PDMS) mold. After degassing in a rough vacuum chamber and
      placed on a sample surface, liquid solution can be aspired through channels and
      cavities created in the PDMS mold. Depending on the composition of the solution
      and the associated drying or incubation processes, a variety of surface patterns
      can be produced without applying external pressure. For demonstration, we
      fabricated agarose gel microwells and biomolecule patterns either on a glass
      plate or in a cell culture Petri dish, both applicable for cell culture studies.

PMID- 19862680
TI  - Psychosocial adjustment of siblings of children with cancer: a systematic review.
AB  - OBJECTIVES: To promote a broader understanding of the psychosocial impact of
      childhood cancer on siblings, a systematic review was undertaken. Directions for
      future research are proposed and clinical strategies are suggested for addressing
      the needs of these children. METHODS: Searches of Medline, PsycINFO and CINAHL
      revealed 65 relevant qualitative, quantitative, or mixed methods' papers
      published between 1997 and 2008. These papers were rated for scientific merit and
      findings were extracted for summary. RESULTS: Siblings of children with cancer do
      not experience elevated mean rates of psychiatric disorders, but a significant
      subset experiences post-traumatic stress symptoms, negative emotional reactions
      (e.g. shock, fear, worry, sadness, helplessness, anger, and guilt), and poor
      quality of life in emotional, family, and social domains. In general, distress is
      greater closer to time of diagnosis. School difficulties are also evident within
      2 years of diagnosis. Qualitative studies reveal family-level themes such as loss
      of attention and status as well as positive outcomes including increased sibling
      maturity and empathy. CONCLUSIONS: Research regarding siblings of children with
      cancer continues to be methodologically limited. The conclusions of qualitative
      and quantitative studies differ considerably. We propose a research agenda to
      propel this field forward including greater attention to alterations in normative
      development (as opposed to psychiatric conditions), development of more
      appropriate quantitative measures, examination of potential moderators of
      adaptation, and use of prospective longitudinal designs. Siblings of children
      with cancer are a psychosocially at-risk group and should be provided with
      appropriate supportive services.

PMID- 19862681
TI  - Pharmacokinetics, bioavailability and effects on electrocardiographic parameters
      of oral fludarabine phosphate.
AB  - The pharmacokinetics, bioavailability and effects on electrocardiographic (ECG)
      parameters of fludarabine phosphate (2F-ara-AMP) were evaluated in adult patients
      with B-cell chronic lymphocytic leukemia. Patients received single doses of
      intravenous (IV) (25 mg/m(2), n=14) or oral (40 mg/m(2), n=42) 2F-ara-AMP. Plasma
      concentrations of drug and metabolites and digital 12-lead ECGs were monitored
      for 23 h after dosing. The dephosphorylated product fludarabine (2F-ara-A) was
      the principal metabolite present in the systemic circulation. Mean (+/-SD)
      elimination half-life did not differ significantly between IV and oral dosage
      groups (11.3+/-4.0 vs 9.7+/-2.0 h, p=0.053). Renal excretion was a major
      clearance pathway, along with transformation to a hypoxanthine metabolite 2F-ara
      Hx. Estimated mean oral bioavailability of 2F-ara-A was 58%. Compared to the time
      matched drug-free baseline Fridericia correction of the QT interval (QTcF), the
      mean QTcF change following 2F-ara-AMP did not differ from zero, and a treatment
      effect of >+10 and >+15 ms could be excluded following oral and IV 2F-ara-AMP,
      respectively. Similarly, heart rate, PR interval and QRS duration did not change
      following 2F-ara-AMP treatment. Thus the 25 mg/m(2) IV and 40 mg/m(2) oral doses
      of 2F-ara-AMP produce similar systemic exposure, and do not prolong QTcF,
      indicating low risk of drug induced Torsades de Pointes.

PMID- 19862682
TI  - The role of appearance investment in the adjustment of women with breast cancer.
AB  - OBJECTIVE: Appearance investment can be considered an important factor in the
      explanation of individual differences in adjustment to breast cancer. This study
      aims to analyze the role of this variable on a set of adjustment outcomes,
      namely, quality of life (QOL), emotional adjustment (depression and anxiety) and
      fear of negative evaluations. The differential role of motivational salience
      facet of appearance investment (MS; the individual's efforts to be or feel
      attractive), conceptualized as a protective factor, and of self-evaluative
      salience facet (SES; the importance an individual places on physical appearance
      for their definition of self-worth), conceptualized as a vulnerability factor, is
      explored. METHODS: This cross-sectional study included 117 Portuguese breast
      cancer patients (mean age=52.47; SD=8.81), on average 2.32 months (SD=2.17) post
      diagnosis. Appearance investment was measured by the ASI-R; QOL by the WHOQOL
      bref; emotional adjustment by the HADS; and fear of negative evaluations by the
      FNE (Portuguese versions). Several hierarchical multiple regressions were
      conducted for each outcome, using investment facets as a predictor variable.
      RESULTS: Both facets of investment contributed to the explanation of social
      (p<or=0.001) and psychological (p<or=0.001) QOL and also depression (p<or=0.001),
      with SES being associated with poorer results and MS with better outcomes. SES
      also predicted higher levels of fear of negative evaluations (p<or=0.001).
      CONCLUSIONS: This study provided significant information about the role of
      appearance investment in the adjustment of breast cancer patients and added
      empirical support to SES-MS distinction.

PMID- 19862683
TI  - Based on a review of the data, use of the term 'cypridinid' solves the
      Cypridina/Vargula dilemma for naming the constituents of the luminescent system
      of ostracods in the family Cypridinidae.
AB  - The luciferin of the ostracod Vargula hilgendorfii (formerly Cypridina
      hilgendorfii) is often termed Cypridina luciferin in the scientific literature,
      but, to avoid ambiguity and based on a review of the literature, is best referred
      to by the more inclusive term cypridinid luciferin. This situation exemplifies
      how new knowledge in systematics and the resulting nomenclatural changes can
      result in evolutionary insights. Similar solutions can probably be applied to
      other taxonomic dilemmas.

PMID- 19862685
TI  - Positron emission tomography kinetic modeling algorithms for small animal
      dopaminergic system imaging.
AB  - Small animal positron emission tomography (PET) imaging allows in vivo
      quantification of lesion- or treatment-induced neurochemical changes in animal
      models of disease. Important for quantification are the kinetic modeling methods
      used to determine biologically-relevant parameters of tracer-tissue interaction.
      In this work, we evaluate modeling algorithms for the dopaminergic tracers (11)C
      dihydrotetrabenazine (DTBZ), (11)C-methylphenidate (MP), and (11)C-raclopride
      (RAC), used to image the dopaminergic system in the unilateral 6-hydroxydopamine
      lesioned rat model of Parkinson's disease. For the presynaptic tracers, PET
      measures are compared with autoradiographic binding measurements using DTBZ and
      [(3)H]WIN 35,428 (WIN). We independently developed a new variant of the tissue
      input Logan graphical modeling method, and compared its performance with the
      simplified Logan graphical method and the simplified reference tissue with basis
      functions method (SRTM), for region of interest (ROI) averaged time activity
      curves (TACs) and parametric imaging. The modified graphical method was found to
      be effectively unbiased by target tissue noise and has advantages for parametric
      imaging, while all tested methods were equivalent for ROI-averaged data.

PMID- 19862686
TI  - Muscarinic receptor blockade in the ventral tegmental area attenuates cocaine
      enhancement of laterodorsal tegmentum stimulation-evoked accumbens dopamine
      efflux in the mouse.
AB  - The reinforcing properties of cocaine have been related to increased
      extracellular concentrations of dopamine in the nucleus accumbens (NAc). M5
      muscarinic acetylcholine receptors (mAChRs) on dopamine cells in the ventral
      tegmental area (VTA) facilitate mesoaccumbens dopamine transmission and are
      critically involved in mediating natural and drug reinforcement. We investigated
      the effects of pharmacological blockade of mAChRs in the VTA on cocaine's ability
      to enhance electrically evoked NAc dopamine efflux. Using fixed potential
      amperometry together with carbon fiber recording microelectrodes positioned in
      the NAc core, we quantified dopamine oxidation currents (dopamine efflux) evoked
      by brief stimulation (15 monophasic pulses at 50 Hz every 30 s) of the
      laterodorsal tegmentum (LDT) in urethane (1.5 g/kg, i.p.) anesthetized mice.
      Compared to predrug baseline responses, cocaine (5 or 10 mg/kg, i.p.) dose
      dependently enhanced LDT stimulation-evoked NAc dopamine efflux, whereas the
      nonsubtype selective mAChR antagonist scopolamine (10 microg/0.5 microl)
      microinfused into the VTA diminished LDT-evoked NAc dopamine efflux. Preinfusion
      of scopolamine into the VTA diminished the facilitatory actions of cocaine on LDT
      stimulation-evoked NAc dopamine efflux, and when infused at the peak effect of
      cocaine attenuated LDT-evoked dopamine efflux to below predrug baseline levels.
      These findings suggest that LDT cholinergic inputs to dopamine neurons in the
      VTA, via activation of mAChRs (probably of the M5 subtype), are involved in
      modulating the facilitatory effects of cocaine on NAc dopamine neurotransmission.
      They also suggest that the development of antagonists aimed at selectively
      disrupting M5 receptor function may be valuable in reducing abuse liability of
      psychostimulants.

PMID- 19862687
TI  - In vivo evaluation of N-[18F]fluoroethylpiperidin-4ylmethyl acetate in rats
      compared with MP4A as a probe for measuring cerebral acetylcholinesterase
      activity.
AB  - [(11)C]MP4A is an established radioprobe for quantification of cerebral
      acetylcholinesterase (AChE) activity by positron emission tomography (PET) based
      on the kinetics of AChE-mediated metabolism and metabolite trapping. It has been
      used to assess the deficiency in cholinergic innervation in the brain of patients
      with dementia. Because (18)F has a longer half-life than (11)C, (18)F-labeled
      derivatives of [(11)C]MP4A allow delivery of the probe to other PET centers,
      making AChE measurement more widely applicable. Previously, N
      [(18)F]fluoroethylpiperidin-4ylmethyl acetate ([(18)F]FEP-4MA) showed that the
      (18)F-labeled analog of MP4A possessed desirable properties for the
      quantification of cerebral AChE activity by PET. Here, we evaluated the in vivo
      kinetics of [(18)F]FEP-4MA and validated the responsiveness of brain uptake to
      AChE activity based on a mathematical model derived from the AChE-mediated
      trapping rationale and compared it with MP4A in rats. Almost all radioactivity in
      the brain was composed of [(18)F]FEP-4MA and the hydrolyzed metabolite at 0-60
      min postinjection. When the authentic radioprobe was not observed in the brain,
      the regional (18)F uptake in the brain correlated well with regional MP4A uptake,
      and the elimination rate of (18)F from the brain was higher than that of the
      metabolite of MP4A. The responsiveness of regional (18)F uptake in the brain was
      examined by simultaneous assay of (18)F concentration, relative blood flow, and
      AChE activity. Regional (18)F uptake correlated with regional AChE activity as
      well as that of MP4A. Therefore, we concluded that [(18)F]FEP-4MA would be
      applicable to clinical PET study for quantifying cerebral AChE activity.

PMID- 19862684
TI  - Early exposure to haloperidol or olanzapine induces long-term alterations of
      dendritic form.
AB  - Exposure of the developing brain to a wide variety of drugs of abuse (e.g.,
      stimulants, opioids, ethanol, etc.) can induce life-long changes in behavior and
      neural circuitry. However, the long-term effects of exposure to therapeutic,
      psychotropic drugs have only recently begun to be appreciated. Antipsychotic
      drugs are little studied in this regard. Here, we quantitatively analyzed
      dendritic architecture in adult mice treated with paradigmatic typical-
      (haloperidol) or atypical (olanzapine) antipsychotic drugs at developmental
      stages corresponding to fetal or fetal plus early childhood stages in humans. In
      layer 3 pyramidal cells of the medial and orbital prefrontal cortices and the
      parietal cortex and in spiny neurons of the core of the nucleus accumbens, both
      drugs induced significant changes (predominantly reductions) in the amount and
      complexity of dendritic arbor and the density of dendritic spines. The drug
      induced plasticity of dendritic architecture suggests changes in patterns of
      neuronal connectivity in multiple brain regions that are likely to be
      functionally significant.

PMID- 19862689
TI  - Ethanol and PTZ effects on siRNA-mediated GABAB1 receptor: down regulation of
      intracellular signaling pathway in prenatal rat cortical and hippocampal neurons.
AB  - GABA(B) receptors (R) are widely expressed and distributed in the nervous system,
      and have been implicated in variety of neurodegenerative and pathophysiological
      disorders. However, the exact molecular mechanism regarding responsibility of
      GABA(B1)R in downstream signaling pathway is not well understood. The present
      study was undertaken to explore the downstream signaling and role of GABA(B1)R
      upon acute ethanol and pentylenetetrazol (PTZ) exposure for (20 min) in cortical
      and hippocampal neuronal cell cultures by using GABA(B1)R RNA interference (i)
      (30 nM, 48 h) at gestational days 17.5. The results showed that GABA(B1)R and
      protein kinase A-alpha (PKA) showed decreased expression upon ethanol and PTZ
      exposure in cortical and hippocampal neurons during transfected and
      nontransfected conditions, whereas these effects could lead to significant
      changes in phosphorylation of cAMP-response element binding protein (p-CREB)
      expression where GABA(B1)R was knocked down. Furthermore, intracellular Ca(+2)
      concentrations were also reduced in some groups after transfection with GABA(B1)R
      RNAi. These results showed a critical role of GABA(B1)R upon ethanol and PTZ
      exposure by modulating downstream signaling pathway. Finally, these findings
      suggested that inhibition of GABA(B1)R results in the modulation of PKA, p-CREB
      pathway may play a role in long-term changes in the nervous system, and may be an
      underlying cause of ethanol's effects.

PMID- 19862688
TI  - Alterations in 5-HT2A receptor binding in various brain regions among 6
      hydroxydopamine-induced Parkinsonian rats.
AB  - The serotonergic system has close interactions with the dopaminergic system and
      is strongly implicated in the pathophysiological mechanisms and therapeutic
      paradigms of Parkinson's disease (PD). This study aims to investigate regional
      changes in 5-hydroxytryptamine (5-HT) 2A receptors in the rat brain 3 weeks after
      unilateral medial forebrain bundle lesion by 6-hydroxydopamine (6-OHDA). 5-HT 2A
      receptor distributions and alterations in the postmortem rat brain were detected
      by [(3)H]ketanserin-binding autoradiography. In the 6-OHDA-induced Parkinson's
      rat model, nigrostriatal dopaminergic neuron loss significantly mediated the
      decreased [(3)H]ketanserin binding, predominantly in the agranular insular cortex
      (17.3%, P = 0.03), cingulate cortex (18.2%, P < 0.001), prefrontal cortex (8%, P
      = 0.043), primary somatosensory cortex (17.7%, P = 0.002), and caudate putamen
      (14.5%, P = 0.02) compared to controls while a profound reduction of tyrosine
      hydroxylase (TH) immunostaining in the striatum was also observed. Alterations in
      [(3)H]ketanserin binding in the examined brain areas may represent the specific
      regions that mediate cognitive dysfunctions via the serotonin system. The
      downregulation of 5-HT(2A) receptor binding in this study also provides indirect
      evidence for plasticity in the serotonergic system in the rat brains. This study
      contributes to a better understanding of the critical roles of 5-HT(2A) receptors
      in treating neurodegenerative disorders and implicates 5-HT(2A) receptors as a
      novel therapeutic target in the treatment of PD.

PMID- 19862691
TI  - Looking past the obvious: experiences of altered masculinity in penile cancer.
AB  - OBJECTIVES: Penile cancer, although statistically rare in Western countries
      (1:100 000 per year), results in considerable physical and psychological
      morbidity. The treatment of choice for penile cancer is either partial or total
      amputation of the penis. Metastatic spread into the surrounding lymphatic system
      may require additional surgery. To date, little is known of the lived experiences
      of men with penile cancer regarding the impact of the disease and its treatment
      on dimensions of masculinity. METHODS: A small-scale qualitative study using
      Interpretative Phenomenological Analysis (IPA). IPA aims at exploring the
      experience of life events and the meaning and implications for the person living
      through them. A purposive sample of men with penile cancer who were within a
      minimum of 18 months post-surgery were recruited via a specialist urology clinic
      (n = 9). Participants were interviewed by a male researcher using a pre-agreed
      semi-structured interview schedule; interviews were audio recorded for
      transcription with detailed analyses of main and sub-themes conducted
      independently by three researchers. To maintain analytical rigour, constant
      comparisons of main and sub-themes were made between the individual transcripts
      and across the emergent themes within the research group. RESULTS: Central themes
      were (1) grappling with reality; (2) learning to cope and (3) changes to self.
      CONCLUSIONS: That men should have an altered sense of masculine identity
      following penile cancer surgery is not unexpected. However, the ways in which
      altered masculinity manifested itself were both subtle and insidious. The results
      have implications for clinical practice and demonstrated the need for further
      research.

PMID- 19862690
TI  - Development and optimization of a cell-based assay for the selection of synthetic
      compounds that potentiate bone morphogenetic protein-2 activity.
AB  - The requirement of large amounts of the recombinant human bone morphogenetic
      protein-2 (BMP-2) produces a huge translational barrier for its routine clinical
      use due to high cost. This leads to an urgent need to develop alternative methods
      to lower costs and/or increase efficacies for using BMP-2. In this study, we
      describe the development and optimization of a cell-based assay that is
      sensitive, reproducible, and reliable in identifying reagents that potentiate the
      effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the
      osteoblastic phenotype. The assay is based on a BMP-responsive Smad1-driven
      luciferase reporter gene. LIM mineralization protein-1 (LMP-1) is a novel
      intracellular LIM domain protein that has been shown by our group to enhance
      cellular responsiveness to BMP-2. Our previous report elucidated that the binding
      of LMP-1 with the WW2 domain in Smad ubiquitin regulatory factor-1 (Smurf1)
      rescues the osteogenic Smads from degradation. Here, using the optimized cell
      based assay, we first evaluated the activity of the recombinantly prepared
      proteins, LMP-1, and its mutant (LMP-1DeltaSmurf1) that lacks the Smurf1-WW2
      domain-binding motif. Both the wild type and the mutant proteins were engineered
      to contain an 11-amino acid HIV-TAT protein derived membrane transduction domain
      to aid the cellular delivery of recombinant proteins. The cell-based reporter
      assay confirmed that LMP-1 potentiates the BMP-induced stimulation of C2C12 cells
      towards the osteoblastic phenotype. The potentiating effect of LMP-1 was
      significantly reduced when a specific-motif known to interact with Smurf1 was
      mutated. We validated the results obtained in the reporter assay by also
      monitoring the expression of mRNA for osteocalcin and alkaline phosphatase (ALP)
      which is widely accepted osteoblast differentiation marker genes. Finally, we
      provide further confirmation of our results by measuring the activity of alkaline
      phosphatase in support of the accuracy and reliability of our cell-based assay.
      Direct delivery of synthesized protein can be limited by high cost, instability
      or inadequate post-translational modifications. Thus, there would be a clear
      benefit for a low cost, cell penetrable chemical compound. We successfully used
      our gene expression-based assay to choose an active compound from a select group
      of compounds that were identified by computational screenings as the most likely
      candidates for mimicking the function of LMP-1. Among them, we selected SVAK-3, a
      compound that showed a dose-dependent potentiation of BMP-2 activity in inducing
      osteoblastic differentiation of C2C12 cells. We show that either the full length
      LMP-1 protein or its potential mimetic compound consistently exhibit similar
      potentiation of BMP-2 activity even when multiple markers of the osteoblastic
      phenotype were parallely monitored.

PMID- 19862692
TI  - Quality-of-life and surgical treatments for rectal cancer--a longitudinal
      analysis using the California Cancer Registry.
AB  - BACKGROUND: Heterogeneous results for research investigating health-related
      quality of life (HRQL) in patients undergoing sphincter-ablating procedures for
      rectal cancer are likely due to single institution experiences and measurement of
      HRQL. To address this heterogeneity, we evaluated HRQL in patients with rectal
      cancer by type of surgery, location of tumor, and receipt of adjuvant therapy
      using an HRQL instrument that has not been used to address rectal cancer patients
      in a population-based sample over time. METHODS: The Functional Assessment of
      Cancer Therapy-Colorectal instrument was administered at 9 and 19 months after
      diagnosis to a consecutive sample of 160 patients in Northern California
      identified by the California Cancer Registry. A broad multidimensional
      interpretation of HRQL was used to examine the impact of tumor location and
      treatment status, stage of disease, age, and gender. RESULTS: In general, men had
      lower social well-being scores, and younger patients had lower physical and
      emotional well-being scores and colorectal concerns scores. We found no
      differences in HRQL by either tumor location or type of surgery, at either 9 or
      19 months after diagnosis. Lower physical well-being and greater adverse
      colorectal concerns were reported at 9 months among patients who received
      adjuvant therapy; however, only adverse colorectal concerns persisted over time.
      CONCLUSIONS: This study provides additional evidence that sphincter-ablating
      procedures do not necessarily reduce quality of life in patients with rectal
      cancer. Distinctive features of this study include a broad multidimensional
      interpretation of HRQL, the 19 months of longitudinal follow-up, and a
      prospective population-based study design.

PMID- 19862694
TI  - Experiencing one's body after a diagnosis of cancer--a phenomenological study of
      young adults.
AB  - Young adults with cancer are still in the process of shaping their lives and are
      therefore at a vulnerable stage. Altered body image may change how patients cope
      with the disease and impact rehabilitation capacity. OBJECTIVE: To describe the
      essence of how young adults with cancer experience their bodies. METHODS:
      Interviews (12 informants), transcribed verbatim. ANALYSIS: Giorgi's
      phenomenological method. RESULTS: Identified themes: experience of 'physical body
      change', 'discomfort', 'the body at the moment without reflecting on the disease
      and treatment', 'body image' and 'grasping the illness'. Essences: The body as
      the bearer of life; conflict between age and disease; manifest changes in
      appearance, physically and mentally; the body no longer a whole; the body as
      influenceable and able to recover and heal. CONCLUSIONS: These patients undergo
      physical and mental changes that affect their self-image and health-related life
      quality. Thus, future studies need to explore interventions that may enhance the
      individual perception of their body.

PMID- 19862693
TI  - Sexual functioning in young adult survivors of childhood cancer.
AB  - BACKGROUND: Studies of sexuality or sexual behavior in childhood cancer survivors
      tend to examine relationships or achievement of developmental milestones but not
      physiological response to cancer or treatment. The purpose of this study is to
      (1) identify prevalence and risk factors for sexual dysfunction in childhood
      cancer survivors, and (2) examine the extent to which sexual dysfunction may be
      associated with health-related quality of life (HRQOL) and psychosocial outcomes.
      METHODS: Five hundred ninety-nine survivors age 18-39 years completed
      standardized measures of sexual functioning, HRQOL, psychological distress and
      life satisfaction. Descriptive statistics assessed prevalence of sexual symptoms.
      Bivariate analyses identified correlates of sexual symptoms and examined
      associations between symptoms and HRQOL/psychosocial outcomes. RESULTS: Most
      survivors appear to be doing well, although 52% of female survivors and 32% of
      male survivors reported at least 'a little of a problem' in one or more areas of
      sexual functioning. Mean symptom score for females was more than twice that of
      males. Sexual symptoms were associated with reporting health problems.
      Significant associations between sexual functioning and HRQOL outcomes were
      observed, with gender differences in strengths of association suggesting that
      males find sexual symptoms more distressing than do females. CONCLUSIONS: While
      most survivors appear to be doing well in this important life domain, some young
      adult survivors report sexual concerns. While female survivors may report more
      sexual symptoms than male survivors, males may experience more distress
      associated with sexual difficulties. Better-specified measures of sexual
      function, behavior and outcomes are needed for this young adult population.

PMID- 19862695
TI  - Identifying functional impairment with scores from the repeatable battery for the
      assessment of neuropsychological status (RBANS).
AB  - OBJECTIVE: To examine the link between RBANS scores and functional impairment.
      Functional status was evaluated through informant report using the clinical
      dementia rating (CDR) scale. METHODS: Archival data were reviewed from records of
      99 patients in a memory disorder clinic (MDC) research database. Consensus-based
      diagnoses were Alzheimer's disease (AD; n = 48), mild cognitive impairment (MCI;
      n = 48), AD with vascular components; (n = 2) and dementia due to psychiatric
      conditions (n = 1). RESULTS: The RBANS language index score was significantly
      related to CDR domain scores of community affairs (p < .01), home and hobbies (p
      < .01), personal care (p < .05), memory (p < 0.01), and judgment (p < 0.01).
      RBANS immediate memory index scores were significantly related to (p < 0.05) the
      CDR Memory and judgment and problem solving domains. Based on these findings,
      follow-up regressions were conducted. Semantic fluency was significantly related
      to CDR memory (p < 0.01), judgment (p < 0.05), community affairs (p < 0.05),
      home/hobbies (p < 0.05), and personal care (p < 0.05) functional domains. Picture
      naming was significantly related to the CDR personal care domain (p < 0.05). List
      learning was significantly related to CDR memory functional domain (p < 0.01) and
      judgment (p < 0.05). Lastly, story memory was significantly related to the CDR
      judgment domain (p < 0.05). CONCLUSIONS: The RBANS may be an indicator of
      functional impairment as well as a neuropsychological testing tool. The use of
      the RBANS could reduce the amount of testing that is administered to the patient,
      or can provide a way to compare other measurements of functional impairment to
      assess accuracy of findings.

PMID- 19862696
TI  - Health and well-being in care staff and their relations to organizational and
      psychosocial factors, care staff and resident factors in nursing homes.
AB  - OBJECTIVE: The aim of this study is to investigate the association of
      psychosocial factors and patient factors with stress in care staff in nursing
      homes. METHODS: In this cross-sectional survey, 197 care staff from 13 dementia
      wards from four nursing homes in the Stavanger region, Norway, participated.
      Stress in care staff was measured by Perceived Stress Scale, Hopkins Symptom
      Check List, and subjective health complaints. Agitation in patients was measured
      with the Cohen-Mansfield Agitation Inventory. Work-related psychosocial factors
      were measured by General Nordic Questionnaire for Psychosocial and Social Factors
      at Work (QPSNordic). Data were analyzed using multivariate regression analyses.
      RESULTS: Psychosocial factors (QPS Nordic) were significantly associated with all
      the three outcome measures of stress in care staff, whereas agitation was
      associated with subjective health complaints only. QPS Nordic subscales
      significantly associated with stress in care staff were those associated with
      leadership. CONCLUSIONS: Psychosocial factors were more important predictors of
      carer stress than patient-related factors such as dementia severity and
      agitation. The findings provide key background information in the planning of
      interventions to improve conditions for care staff and ultimately for nursing
      home residents.

PMID- 19862697
TI  - Step-by-step: the effects of physical practice on the neural correlates of
      locomotion imagery revealed by fMRI.
AB  - Previous studies have shown that mental imagery is a suitable tool to study the
      progression of the effect of practice on brain activation. Nevertheless, there is
      still poor knowledge of changes in brain activation patterns during the very
      early stages of physical practice. In this study, early and late practice stages
      of different kinds of locomotion (i.e., balanced and unbalanced) have been
      investigated using functional magnetic resonance imaging during mental imagery of
      locomotion and stance. During the task, cardiac activity was also recorded. The
      cerebral network comprising supplementary motor area, basal ganglia, bilateral
      thalamus, and right cerebellum showed a stronger activation during the imagery of
      locomotion with respect to imagery of stance. The heart beat showed a significant
      increase in frequency during the imagery of locomotion with respect to the
      imagery of stance. Moreover, early stages of practice determined an increased
      activation in basal ganglia and thalamus with respect to late stages. In this
      way, it is proposed the modulation of the brain network involved in the imagery
      of locomotion as a function of physical practice time.

PMID- 19862698
TI  - Regional impact of field strength on voxel-based morphometry results.
AB  - The objective of this study was to characterize the sensitivity of voxel-based
      morphometry (VBM) results to choice field strength. We chose to investigate the
      two most widespread acquisition sequences for VBM, FLASH and MP-RAGE, at 1.5 and
      3 T. We first evaluated image quality of the four acquisition protocols in terms
      of SNR and image uniformity. We then performed a VBM study on eight subjects
      scanned twice using the four protocols to evaluate differences in grey matter
      (GM) density and corresponding scan-rescan variability, and a power analysis for
      each protocol in the context a longitudinal and cross-sectional VBM study. As
      expected, the SNR increased significantly at 3 T for both FLASH and MP-RAGE.
      Image non-uniformity increased as well, in particular for MP-RAGE. The
      differences in CNR and contrast non-uniformity cause regional biases between
      protocols in the VBM results, in particular between sequences at 3 T. The power
      analysis results show an overall decrease in the number of subjects required in a
      longitudinal study to detect a difference in GM density at 3 T for MP-RAGE, but
      an increase for FLASH. The number of subjects required in a cross-sectional VBM
      study is higher at 3 T for both sequences. Our results show that each protocol
      has a distinct regional sensitivity pattern to morphometric change, which goes
      against the classical view of VBM as an unbiased whole brain analysis technique,
      complicates the combination of data within a VBM study and the direct comparison
      of VBM studies based on different protocols.

PMID- 19862700
TI  - Amyloid precursor protein expression is induced by tumor necrosis factor alpha in
      3T3-L1 adipocytes.
AB  - Amyloid precursor protein (APP) has been characterized as an adipocyte-secreted
      protein that might contribute to obesity-related insulin resistance,
      inflammation, and dementia. In the current study, regulation of APP by the
      proinflammatory and insulin resistance-inducing cytokine tumor necrosis factor
      (TNF) alpha was determined in 3T3-L1 adipocytes. Interestingly, APP protein
      synthesis and mRNA expression were significantly increased by TNFalpha in a time
      dependent manner with maximal induction observed after 24 h of treatment.
      Furthermore, TNFalpha induced APP mRNA expression dose-dependently with maximal
      6.4-fold upregulation seen at 100 ng/ml effector. Moreover, inhibitor experiments
      suggested that TNFalpha-induced APP expression was mediated by nuclear factor
      kappa B. Taken together, we show for the first time a potent upregulation of APP
      by TNFalpha suggesting a potential role of this adipocyte-secreted protein in
      TNFalpha-induced insulin resistance and inflammatory disease.

PMID- 19862699
TI  - The cofilin activity cycle in lamellipodia and invadopodia.
AB  - The actin severing protein cofilin is essential for directed cell migration and
      chemotaxis, in many cell types and is also important for tumor cell invasion
      during metastasis. Through its severing activity, cofilin increases the number of
      free barbed ends to initiate actin polymerization for actin-based protrusion in
      two distinct subcellular compartments in invasive tumor cells: lamellipodia and
      invadopodia. Cofilin severing activity is tightly regulated and multiple
      mechanisms are utilized to regulate cofilin activity. In this prospect, we have
      grouped the primary on/off regulation into two broad categories, both of which
      are important for inhibiting cofilin from binding to F-actin or G-actin: (1)
      Blocking cofilin activity by the binding of cofilin to either PI(4,5)P(2) at
      lamellipodia, or cortactin at invadopodia. (2) Blocking cofilin's ability to bind
      to actin via serine phosphorylation. Although the literature suggests that these
      cofilin regulatory mechanisms may be cell-type dependent, we propose the
      existence of a common cofilin activity cycle in which both operate. In this
      common cycle, the mechanism used to initiate cofilin activity is determined by
      the starting point in the cycle in a given subcellular compartment.

PMID- 19862701
TI  - Pre-fractionation of rat liver cytosol proteins prior to mass spectrometry-based
      proteomic analysis using tandem biomimetic affinity chromatography.
AB  - Efficient and high resolution separation of the protein mixture prior to trypsin
      digestion and mass spectrometry (MS) analysis is generally used to reduce the
      complexity of samples, an approach that highly increases the probability of
      detecting low-copy-number proteins. Our laboratory has constructed an affinity
      ligand library composed of thousands of ligands with different protein absorbance
      effects. Structural differences between these ligands result in different non
      bonded protein-ligand interactions, thus each ligand exhibits a specific affinity
      to some protein groups. In this work, we first selected out several synthetic
      affinity ligands showing large band distribution differences in proteins
      absorbance profiles, and a tandem composition of these affinity ligands was used
      to distribute complex rat liver cytosol into simple subgroups. Ultimately, all
      the fractions collected from tandem affinity pre-fractionation were digested and
      then analyzed by LC-MS/MS, which resulted in high confidence identification of
      665 unique rat protein groups, 1.8 times as many proteins as were detected in the
      un-fractionated sample (371 protein groups). Of these, 375 new proteins were
      identified in tandem fractions, and most of the proteins identified in un
      fractionated sample (290, 80%) also emerged in tandem fractions. Most
      importantly, 430 unique proteins (64.7%) only characterized in specific
      fractions, indicating that the crude tissue extract was well distributed by
      tandem affinity fractionation. All detected proteins were bioinformatically
      annotated according to their physicochemical characteristics (such as MW, pI,
      GRAVY value, TM Helices). This approach highlighted the sensitivity of this
      method to a wide variety of protein classes. Combined usage of tandem affinity
      pre-fractionation with MS-based proteomic analysis is simple, low-cost, and
      effective, providing the prospect of broad application in proteomics.

PMID- 19862702
TI  - Binge eating, purging, or both: eating disorder psychopathology findings from an
      internet community survey.
AB  - OBJECTIVE: This study aimed to compare bulimia nervosa (BN), binge eating
      disorder (BED), and purging disorder (PD) on clinically significant variables and
      examine the utility of once versus twice-weekly diagnostic thresholds for
      disturbed eating behaviors. METHOD: 234 women with BN, BED, or PD were identified
      through self-report measures via an online survey and categorized based on either
      once-weekly or twice-weekly disturbed eating behaviors. RESULTS: BN emerged as a
      more severe disorder than BED and PD. The three groups differed significantly in
      self-reported restraint and disinhibition and the BN and BED groups reported
      higher levels of depression than PD. For BN, those engaging in behaviors twice
      weekly versus once-weekly were more symptomatic. DISCUSSION: The BN, BED, and PD
      groups differed in clinically meaningful ways. Future research need to clarify
      the relationship between mood disturbances and eating behaviors. Reducing the
      twice-weekly behavior threshold for BN would capture individuals with clinically
      significant eating disorders, though the twice-weekly threshold may provide
      important information about disorder severity for both BN and BED.

PMID- 19862703
TI  - [Climate change and global warming. Towards the global spread of tropical
      infectious diseases? Climate Change and Global Warming].

PMID- 19862706
TI  - [Editorial: Pharmazie in unserer Zeit 6/2009 ].

PMID- 19862708
TI  - [New hope for malaria vaccine].

PMID- 19862709
TI  - [A way out of a malaria-resistance?].

PMID- 19862710
TI  - [What is special about the new swine flu virus?].

PMID- 19862712
TI  - [Tea drinking against malaria?].

PMID- 19862713
TI  - [Drug discovery and development of vaccination strategies for the treatment and
      prevention of cutaneous leishmaniasis].

PMID- 19862714
TI  - [Agents for the treatment of leishmaniasis. Antimony, and more].

PMID- 19862715
TI  - [African sleeping sickness. An ancient threat returns].

PMID- 19862717
TI  - [From onions to artemisinin. Brief history of malaria chemotherapy].

PMID- 19862718
TI  - [The most important tropical infectious disease. Malaria].

PMID- 19862719
TI  - [Active agents and resistance mechanisms. Medicinal Chemistry of drugs against
      malaria].

PMID- 19862720
TI  - [Drugs against malaria: What's in the pipeline? Little new in the fight against
      malaria].

PMID- 19862721
TI  - [Monkeys, humans and malaria. Monkey malaria - for people too dangerous!].

PMID- 19862727
TI  - [Agents for the treatment of African sleeping sickness. Those developed in the
      last century].

PMID- 19862728
TI  - [Problem of counterfeit medicines in Africa and Southeast Asia. Fake anti-malaria
      drugs and more].

PMID- 19862729
TI  - [Successful concept: proteases as targets for anti-infectives. New targets in the
      treatment of infection].

PMID- 19862736
TI  - Electrokinetic sample injection for high-sensitivity CZE (part 2): improving the
      quantitative repeatability and application of electrokinetic supercharging-CZE to
      the detection of atmospheric electrolytes.
AB  - Electrokinetic supercharging (EKS) is defined as a technique that combines
      electrokinetic sample injection with transient ITP. Quantitative repeatability of
      EKS-CZE and the other CE methods using electrokinetic sample injection process is
      usually inferior in comparison with the CE methods using hydrodynamic or
      hydrostatic injection. This is due to some effects, such as the temperature
      change and the convection of the sample solution in the reservoir, as well as the
      change of the distance between an electrode and a capillary end (D(ec)). In
      particular, we have found that the D(ec) change might most seriously affect the
      repeatability, especially when the electrode is a thin Pt wire that could be
      unintentionally bent during sampling. By using a Teflon spacer to fix D(ec) to
      1.1 mm, the RSD of peak area (n=5) was decreased from 20 to 3.4% in EKS-CZE for
      several metal cations. This D(ec) dependence of the sample amount injected was
      supported by computer simulation using CFD-ACE+ software. The improved
      repeatability (down to 5.1% at n=5, averaged RSD for Co(2+), Li(+), Ni(2+),
      Zn(2+) and Pb(2+)) was also experimentally attained by increasing the D(ec) to
      ca. 20 mm, which was also effective to obtain high sensitivity. Since the
      temperature and the convection effects on the repeatability are comparatively
      small in a proper laboratory environment, these effects were estimated from the
      EKS-CZE experiments using conditions such as warming and agitating the sample
      solution during EKS process. Finally, EKS-CZE was applied to the detection of
      ions from atmospheric electrolytes in high-purity water exposed to ambient air
      for 2 h. The microgram per liter levels of anions (chloride, sulfate, nitrate,
      formate, acetate and lactate) and cations (ammonium, calcium, sodium and
      magnesium) could be detected using conventional UV detector.

PMID- 19862737
TI  - Molecular characterization of selected dermatophytes and their identification by
      electrophoretic mutation scanning.
AB  - Dermatophytes are fungi that can be contagious and cause infections in the
      keratinized skin of mammals, including humans. The etiological diagnosis of
      dermatophytosis relies on a combination of in vitro-culture and microscopic
      methods. Effective molecular tools could overcome the limitations of conventional
      methods of identification. In the present study, following phenetic
      identification as M. canis, M. fulvum, M. gypseum, T. mentagrophytes and T.
      terrestre, we genetically characterized key dermatophytes, employing the
      sequences of the first and second internal transcribed spacers of nuclear
      ribosomal DNA as well as part of the chitin synthase-1 gene, and assessed the
      utility of these DNA regions (based on levels of nucleotide variation within and
      among species/taxa) as markers for the classification of species and genotypes.
      Employing partial chitin synthase-1 gene as the marker, we also established a PCR
      coupled SSCP approach as a diagnostic/analytical mutation-scanning tool. This
      tool should facilitate fundamental investigations of the ecology, epidemiology
      and population genetics of dermatophytes and, importantly, should assist in
      allowing a more rapid diagnosis of dermatophytoses in humans and other animals,
      thus overcoming the significant delays in targeted chemotherapy following
      diagnosis using conventional methods. (Nucleotide sequence data reported in this
      paper are available in the EMBL, GenBank and DDJB datadases under accession
      numbers FJ897707-FJ897713 (ITS-1), FJ897714-FJ897720 (ITS-2) and FJ897700
      FJ897706 (pchs-1)).

PMID- 19862738
TI  - Optimization of urinary pteridine analysis conditions by CE-LIF for clinical use
      in early cancer detection.
AB  - The second leading cause of death in the US is cancer and early discovery of the
      disease has translated into reduced fatality rates. We have identified and
      performed a systematic investigation of a method for urinary pteridine analysis
      by using CE-LIF, which is believed to possess the potential to diagnose the
      presence of cancer even earlier than existing methodologies. Through system
      enhancements, we have been able to improve the resolution of the two least
      resolved sets of peaks (6,7-dimethylpterin versus 6-biopterin and D-(+)-neopterin
      versus 6-hydroxymethylpterin) from 0.85 to 2.48 and 0.90 to 3.58, respectively.
      Additionally, we have discovered that the preparation of the urine samples in
      previous works was inadequate, and we have corrected the method to fully oxidize
      the pteridines in the urine, resulting in significantly less variability in
      quantification and greater ease of defining p-values for healthy versus cancer
      patients. Finally, we have performed validation steps of spike and recovery and
      short-term aging studies to demonstrate the method's robustness. As a result, we
      present an optimized and validated method ready for transfer from discovery phase
      to clinical trial that can potentially act as a non-invasively pre-screening test
      for cancer.

PMID- 19862739
TI  - Subcomplexes of mitochondrial complex V reveal mutations in mitochondrial DNA.
AB  - Complex V, site of the final step in oxidative phosphorylation, uses the proton
      gradient across the inner mitochondrial membrane for the production of ATP. It is
      a multi-subunit complex composed of a catalytic domain (F(1)) and a membrane
      domain (F(0)) linked by two stalks. Subcomplexes of complex V containing the F(1)
      domain have previously been reported in small series of patients. We report the
      results in tissue samples and/or cultured skin fibroblasts studied by blue native
      PAGE followed by activity staining in the gel. Catalytically active subcomplexes
      of complex V were detected in 66 tissues originating from 53 patients. In 29 of
      the latter (55%), a mitochondrial DNA (mtDNA) defect was identified. Twelve
      patients had a pathogenic point mutation in a mitochondrial tRNA, one a large
      mtDNA deletion, 12 showed mtDNA depletion and four had a mutation in the MT-ATP6
      gene. We conclude that the presence of subcomplexes of complex V is a valuable
      indicator in the detection of mtDNA defects.

PMID- 19862742
TI  - Modeling of 2-D DNA display.
AB  - 2-D display is a fast and economical way of visualizing polymorphism and
      comparing genomes, which is based on the separation of DNA fragments in two
      steps, first according to their size and then to their sequence composition. In
      this article, we present an exhaustive study of the numerical issues associated
      with a model aimed at predicting the final absolute locations of DNA fragments in
      2-D display experiments. We show that simple expressions for the mobility of DNA
      fragments in both dimensions allow one to reproduce experimental final absolute
      locations better than experimental uncertainties. However, our simulations also
      point out that the results of 2-D display experiments are not sufficient to
      determine the best set of parameters for the modeling of fragments separation in
      the second dimension and that additional detailed measurements of the mobility of
      a few sequences are necessary to achieve this goal. We hope that this work will
      help in establishing simulations as a powerful tool to optimize experimental
      conditions without having to perform a large number of preliminary experiments
      and to estimate whether 2-D DNA display is suited to identify a mutation or a
      genetic difference that is expected to exist between the genomes of closely
      related organisms.

PMID- 19862743
TI  - Applications of MALDI-TOF MS to large-scale human mtDNA population-based studies.
AB  - Analysis of the mitochondrial DNA variation in populations is commonly carried
      out in many fields of biomedical research. We propose the analysis of
      mitochondrial DNA coding region SNP (mtSNP) variation to a high level of
      phylogenetic resolution based on MALDI-TOF MS. The African phylogeny has been
      chosen to test the applicability of the technique but any other part of the
      worldwide phylogeny (or any other mtSNP panel) could be equally suitable for
      MALDI-TOF MS genotyping. SNP selection thus aimed to fully cover all the mtSNPs
      defining major and minor branches of the known African tree, including, macro
      haplogroup L, and haplogroups M1, and U6. A total of 230 mtSNPs were finally
      selected. We used tests samples collected from two different African locations,
      namely, Mozambique and Chad Basin. Different internal genotyping controls and
      other indirect approaches (e.g. phylogenetic checking coupled with automatic
      sequencing) were used in order to evaluate the reproducibility of the technique,
      which resulted to be 100% using samples previously subjected to whole genome
      amplification. The advantages of the MALDI-TOF MS are also discussed in
      comparison with other popular methods such as minisequencing, highlighting its
      high-throughput nature, which is particularly suitable for case-control medical
      studies, forensic databasing or population and anthropological studies.

PMID- 19862744
TI  - Visual DNA as a diagnostic tool.
AB  - We report on the incorporation of the Visual DNA concept in a genotyping assay as
      a simple and straightforward detection tool. The principle of trapping
      streptavidin-coated superparamagnetic beads of micrometer size for visualization
      of genetic variances is used for PrASE-based detection of a panel of mutations in
      the severe and common genetic disorder of cystic fibrosis. The method allows a
      final investigation of genotypes by the naked eye and the output is easily
      documented using a regular hand-held device with an integrated digital camera. A
      number of samples were run through the assay, showing rapid and accurate
      detection using superparamagnetic beads and an off-the-shelf neodymium magnet.
      The assay emphasizes the power of Visual DNA and demonstrates the potential value
      of the method in future point-of-care tests.

PMID- 19862745
TI  - Steady-state electrophoresis of RNA against a gradient of cationic charges in a
      polyacrylamide matrix.
AB  - A novel method for separation of RNA fragments is reported here, based on
      migrating the polyanionic RNA fragments in a polycationic polyacrylamide gel,
      made by incorporating positively charged monomers (the Immobilines used for
      creating immobilized pH gradients) into the neutral polyacrylamide backbone.
      Separations are typically performed in a 0-10 mM, pK 10.3 Immobiline gradient
      under denaturing conditions (6 M urea). In the 100-1000 bp length, it is shown
      that separations of RNA are optimal and very sharp bands can be obtained, in
      comparison with conventional electrophoresis, due to the "focusing" effect
      originated by the charge balancing between the positively charged gel matrix and
      the negatively charged RNA species. Excellent separations are also obtained from
      micro-RNAs, single-stranded RNA molecules of 21-23 nucleotides in length, which
      appear to regulate gene expression in animal and plant tissues. As a third
      example, 2-D runs in control and polycationic gels are shown. Under native
      conditions, RNAs are not aligned in a diagonal, suggesting that molecular shape
      has a strong influence on the interaction between RNA and the charged gel matrix.
      Thus, 2-D runs in cationic matrices might be exploited for structural studies of
      RNA molecules.

PMID- 19862746
TI  - Measurement of electrophoretic mobility of cardiomyocytes.
AB  - The electrophoretic mobility (EPM) of rat cardiomyocytes with or without the
      treatment of neuraminidase was studied by cell electrophoresis. The EPM was found
      to change over a range from 0 to 8.67 microm s(-1)/V cm(-1), depending on ionic
      strength, transmembrane potential, pH value, and/or surface charges. It is
      interesting that zero EPM was observed but reverse of the mobility was not. These
      results suggested that the negative charges carried on the cardiomyocyte surface
      might comprehensively consist of surface sialic acid, plasmalemma proteins,
      phospholipids, and transmembrane potential. The aberrant electrical double layer
      formed between the carried negative charges and adions had a big adsorption layer
      and a diffusion layer whose sizes changed circularly, making only negative
      charges be carried on the surface of living cardiomyocytes. The special
      structures on the surface of cardiomyocytes probably play a considerable role in
      the process of cardiac electrical activity.

PMID- 19862747
TI  - Comparison of methods for quantification of subtle splice variants.
AB  - Alternative splicing is capable of generating multiple mRNA variants from a
      single gene and is hence a key mediator of molecular diversity generated at the
      transcript level. Consequently, delivering quantitative information on the
      fractions of splice variants is essential for the understanding of their
      biological roles. Here we compare techniques for subtle splice variant
      quantification that are able to resolve length differences as small as one
      nucleotide: PAGE with ethidium-bromide densitometry, pyrosequencing, and CE-LIF.
      We give comprehensive descriptions of assay designs and calibration procedures
      and present an evaluation of these methods in terms of accuracy, reproducibility
      and applicability. We also examined template concentrations and reverse
      transcription-coupled PCR conditions as potential cause of biased results as they
      were observed for extreme low template concentrations and/or PCR amplicons with
      size differences of 195 nt. As proof of concept, we determine the splice ratios
      of variants differing by 3 and 12 nt in five human tissues. We demonstrate that
      CE-LIF is the most precise and also the most labor- and time-efficient method.

PMID- 19862748
TI  - A new multiplex for human identification using insertion/deletion polymorphisms.
AB  - Human identification is usually based on the study of STRs or SNPs depending on
      the particular characteristics of the investigation. However, other types of
      genetic variation such as insertion/deletion polymorphisms (indels) have
      considerable potential in the field of identification, since they can combine the
      desirable characteristics of both STRs and SNPs. In this study, a set of 38 non
      coding bi-allelic autosomal indels reported to be polymorphic in African,
      European, and Asian populations were selected. We developed a sensitive
      genotyping assay, which is able to characterize all 38 bi-allelic markers using a
      single multiplex PCR and detected with standard CE analyzers. Amplicon length was
      designed to be shorter than 160 bp. Complete profiles were obtained using 0.3 ng
      of DNA, and full genotyping of degraded samples was possible in cases where
      standard STR typing had partially failed. A total of 306 individuals from Angola,
      Mozambique, Portugal, Macau, and Taiwan were studied and population data are
      presented. All indels were polymorphic in the three population groups studied and
      the random match probabilities of the set ranged in orders of magnitude from 10(
      14) to 10(-15). Therefore, the indel-plex represents a valuable approach in human
      identification studies, especially in challenging DNA cases, as a more
      straightforward and efficient alternative to SNP typing.

PMID- 19862749
TI  - Preliminary results for 2-D separation with high-performance thin-layer
      chromatography and pressurized planar electrochromatography.
AB  - Preliminary results of 2-D separation of test dye mixture using high-performance
      thin-layer chromatography (HPTLC) and pressurized planar electrochromatography
      (PPEC) are demonstrated. The advantage of 2-D HPTLC/PPEC separation is based on
      different separation selectivities obtained in both HPTLC and PPEC systems. HPTLC
      RP18 W plates of 5x20 cm from Merck were used in the investigations. In the first
      dimension, a HPTLC process was performed using 5 cm length of the plate and in
      the second dimension PPEC separation was obtained applying plate of 20 cm length.
      PPEC process followed prewetting the chromatographic plate with sample zones on
      it, which were partly separated after first dimensional (HPTLC) separation. In
      the experiments, the modified version of PPEC device for 20 cm long
      chromatographic plate and the reservoir for prewetting the adsorbent layer were
      applied.

PMID- 19862750
TI  - Using of chicken antibodies for metallothionein detection in human blood serum
      and cadmium-treated tumour cell lines after dot- and electroblotting.
AB  - Metallothionein (MT) is a low-molecular mass protein playing an essential role in
      homeostasis of heavy metal ions. Its relation with formation and progression of a
      tumour disease is discussed in this article. Here, we propose a new
      methodological approach for visualization of MT on PVDF membranes after dot- and
      electroblotting by using a commercial mouse monoclonal antibody E9 and polyclonal
      chicken antibodies. The optimized procedure was as follows. We dotted 1 microL
      sample volume on PVDF membrane and let it to dry. Then, we blocked the membrane
      surface with 2% BSA in PBS for 30 min. After that, the membrane was incubated in
      chicken primary antibody (diluted 1:500), washed, and incubated in rabbit-anti
      chicken secondary antibody conjugated with horseradish peroxidase. To visualize
      the interaction, we used 3-aminoethyl-9-carbazole. Under these conditions, we
      estimated detection limit as 3 pg of MT per 1 microL. The optimal approach was
      further utilized for detection of MT level in two human fibroblast cell lines and
      in blood serum obtained from children with medulloblastoma. The results were in
      good agreement with differential pulse voltammetry-Brdicka reaction.

PMID- 19862751
TI  - De novo peptide sequencing by tandem MS using complementary CID and electron
      transfer dissociation.
AB  - De novo sequencing of peptides using tandem MS is difficult due to missing
      fragment ions in the spectra commonly obtained after CID of peptide precursor
      ions. Complementing CID spectra with spectra obtained in an ion-trap mass
      spectrometer upon electron transfer dissociation (ETD) significantly increases
      the sequence coverage with diagnostic ions. In the de novo sequencing algorithm
      CompNovo presented here, a divide-and-conquer approach was combined with an
      efficient mass decomposition algorithm to exploit the complementary information
      contained in CID and ETD spectra. After optimizing the parameters for the
      algorithm on a well-defined training data set obtained for peptides from nine
      known proteins, the CompNovo algorithm was applied to the de novo sequencing of
      peptides derived from a whole protein extract of Sorangium cellulosum bacteria.
      To 2406 pairs of CID and ETD spectra contained in this data set, 675 fully
      correct sequences were assigned, which represent a success rate of 28.1%. It is
      shown that the CompNovo algorithm yields significantly improved sequencing
      accuracy as compared with published approaches using only CID spectra or combined
      CID and ETD spectra.

PMID- 19862752
TI  - Application of MEKC and monolithic CEC for the analysis of bioactive
      naphthoquinones in Eleutherine americana.
AB  - Two microscale separation techniques for the analysis of bioactive
      naphthoquinones in Eleutherine americana were developed and validated. By MEKC
      four compounds (eleuthoside B, isoeleutherin, eleutherol and eleutherinoside A)
      could be determined in plant extracts using an aqueous electrolyte solution
      composed of 25 mM sodium tetraborate, 50 mM sodium cholate and 20% THF. CEC on a
      polymeric methacrylate-based monolith with strong cationic properties showed
      promising results, as it additionally enabled the separation of two enantiomers,
      eleutherin and isoeleutherin. The mobile phase for CEC experiments comprised 3 mM
      ammonium formate in a mixture of ACN and water. At an applied voltage of -25 kV,
      all five markers were baseline separated in less than 12 min. Both methods were
      successfully validated for linearity (MEKC: R(2) > or = 0.999; CEC: R(2) > or =
      0.997), sensitivity (MEKC: LOD = 4-5 microg/mL; CEC: LOD=2-8 microg/mL), accuracy
      (MEKC: 96.5-102.7% recovery; CEC: 97.1-103.5% recovery) and precision (MEKC:
      sigma(rel) < or = 2.43%; CEC: sigma(rel) < or = 2.21%). The quantitative analysis
      of naphthoquinone derivatives in several E. americana samples showed that both
      methods are suitable for practical applications, because the results were well
      comparable to those obtained by established techniques such as HPLC.

PMID- 19862753
TI  - Postcolumn derivatization of proteins in capillary sieving electrophoresis/laser
      induced fluorescence detection.
AB  - The separation methods for proteins with high resolution and sensitivity are
      absolutely important in the field of biological sciences. Capillary sieving
      electrophoresis (CSE) is an excellent separation technique for DNA and proteins
      with high resolution, while LIF permits the most sensitive detection in CSE.
      Therefore, proteins have to be labeled with fluorescent or fluorogenic reagent to
      produce fluorescent derivatives. Both precolumn and oncolumn derivatization have
      been employed for the labeling of proteins in CSE. However, there is no report on
      the postcolumn derivatization due to the limitation in the use of a standard
      migration buffer, despite it being a promising method for sensitive detection of
      proteins. Here, we show a novel postcolumn derivatization method for protein
      separation by CSE, using a tertiary amine as a buffer component in the running
      buffer. Tris, which is commonly used as a base in CSE separation buffers, was
      substituted by tertiary amines, 2-(diethylamino)ethanol and triethanolamine. A
      buffer solution containing 2-(diethylamino)ethanol or triethanolamine can be used
      for the CSE separation followed by the postcolumn derivatization of proteins,
      since both reagents are unreactive toward a fluorogenic labeling reagent,
      naphthalene-2,3-dicarbaldehyde. Thus, LIF detection using the postcolumn
      derivatization permits significant reduction in the LOD (by a factor of 2.4-28)
      of proteins, compared with conventional absorbance detection.

PMID- 19862759
TI  - HUPO Highlights.

PMID- 19862760
TI  - Comparative proteome and transcriptome analyses of embryonic stem cells during
      embryoid body-based differentiation.
AB  - Gene expression analyses of embryonic stem cells (ESCs) will help to uncover or
      further define signaling pathways and molecular mechanisms involved in the
      maintenance of self-renewal and pluripotency. We employed a 2-DE-based proteomics
      approach to analyze human ESC line, Royan H5, in undifferentiated cells and
      different stages of spontaneous differentiation (days 3, 6, 12, and 20) by
      embryoid body formation. Out of 945 proteins reproducibly detected on gels, the
      expression of 96 spots changed during differentiation. Using MS, 87 ESC
      associated proteins were identified including several proteins involved in cell
      proliferation, cell apoptosis, transcription, translation, mRNA processing, and
      protein folding. Transcriptional changes accompanying differentiation of Royan H5
      were also analyzed using microarrays. We developed a comprehensive data set that
      shows the use of human ESC lines in vitro to mimic gastrulation and
      organogenesis. Our results showed that proteomics and transcriptomics data are
      complementary rather than duplicative. Although regulation of many genes during
      differentiation were observed only at transcript level, modulation of several
      proteins was revealed only by proteome analysis.

PMID- 19862761
TI  - Comparative analyses of the proteomes of leaves and flowers at various stages of
      development reveal organ-specific functional differentiation of proteins in
      soybean.
AB  - The functional differentiation of protein networks in individual organs and
      tissues of soybean at various developmental stages was investigated by proteomic
      approach. Protein extraction by Mg/NP-40 buffer followed by alkaline phenol-based
      method was optimized for proteomic analysis. Proteome analyses of leaves at
      various developmental stages showed 26 differentially expressed proteins, wherein
      proteins in translocon at the outer/inner envelope membrane of chloroplast
      protein-transport machineries increased significantly at the first trifoliate.
      Immunoblot analysis showed chaperonin-60 expressed abundantly in young leaves,
      whereas HSP 70 and ATP-synthase beta were constitutively expressed in all
      tissues. The net photosynthesis rate and chlorophyll content showed an age
      dependent correlation in leaves. These results suggest that proteins involved in
      carbon assimilation, folding and assembly, and energy may work synchronously and
      show a linear correlation to photosynthesis at developmental stages of leaves.
      Comparison of flower bud and flower proteome reveals 29 differentially expressed
      proteins, wherein proteins involved in mitochondrial protein transport and
      assembly, secondary metabolism, and pollen-tube growth were up-regulated during
      flower development. Together, these results suggest that during developmental
      stages, each type of tissue is associated with a specific group of proteins;
      wherein proteins involved in energy, sugar metabolism, and folding, assembly, and
      destination may play pivotal roles in the maturation process of each organ or
      tissue.

PMID- 19862762
TI  - Median-modified Wiener filter provides efficient denoising, preserving spot edge
      and morphology in 2-DE image processing.
AB  - Denoising is a fundamental early stage in 2-DE image analysis strongly
      influencing spot detection or pixel-based methods. A novel nonlinear adaptive
      spatial filter (median-modified Wiener filter, MMWF), is here compared with five
      well-established denoising techniques (Median, Wiener, Gaussian, and Polynomial
      Savitzky-Golay filters; wavelet denoising) to suggest, by means of fuzzy sets
      evaluation, the best denoising approach to use in practice. Although median
      filter and wavelet achieved the best performance in spike and Gaussian denoising
      respectively, they are unsuitable for contemporary removal of different types of
      noise, because their best setting is noise-dependent. Vice versa, MMWF that
      arrived second in each single denoising category, was evaluated as the best
      filter for global denoising, being its best setting invariant of the type of
      noise. In addition, median filter eroded the edge of isolated spots and filled
      the space between close-set spots, whereas MMWF because of a novel filter effect
      (drop-off-effect) does not suffer from erosion problem, preserves the morphology
      of close-set spots, and avoids spot and spike fuzzyfication, an aberration
      encountered for Wiener filter. In our tests, MMWF was assessed as the best choice
      when the goal is to minimize spot edge aberrations while removing spike and
      Gaussian noise.

PMID- 19862764
TI  - Analysis of interaction partners of H4 histone by a new proteomics approach.
AB  - We describe a modification of the tandem affinity purification method for
      purification and analysis of multiprotein complexes, termed here DEF-TAP (for
      differential elution fractionation after tandem affinity purification). Its
      essential new feature is the use for last purification step of 6xHis-Ni(++)
      interaction, which is resistant to a variety of harsh washing conditions,
      including high ionic strength and the presence of organic solvents. This allows
      us to use various fractionation schemes before the protease digestion, which is
      expected to improve the coverage of the analyzed protein mixture and also to
      provide an additional insight into the structure of the purified macromolecular
      complex and the nature of protein-protein interactions involved. We illustrate
      our new approach by analysis of soluble nuclear complexes containing histone H4
      purified from HeLa cells. In particular, we observed different fractionation
      patterns of HAT1 and RbAp46 proteins as compared with RbAp48 protein, all
      identified as interaction partners of H4 histone. In addition, we report all
      components of the licensing MCM2-7 complex and the apoptosis-related DAXX protein
      among the interaction partners of the soluble H4. Finally, we show that HAT1
      requires N-terminal tail of H4 for its stable association with this histone.

PMID- 19862763
TI  - Proteome changes in human bronchoalveolar cells following styrene exposure
      indicate involvement of oxidative stress in the molecular-response mechanism.
AB  - Styrene is a volatile organic compound that is widely used as an intermediate in
      many industrial settings. There are known adverse health effects at
      environmentally significant concentrations, but little is known about the
      molecular effect of exposure to styrene at sub-acute toxic concentrations. We
      exposed human lung epithelial cells, at a wide range of concentrations (1 mg/m(3)
      10 g/m(3)), to styrene and analyzed the effects on the proteome level by 2-DE,
      where 1380 proteins spots were detected and 266 were identified unambiguously by
      MS. A set of 16 protein spots were found to be significantly altered due to
      exposure to styrene at environmentally significant concentrations of 1-10 mg/m(3)
      (0.2-2.3 ppm). Among these, superoxide dismutase as well as biliverdin reductase
      A could be correlated with the molecular pathway of oxidative stress, while
      eukaryotic translation initiation factor 5A-1, ezrin, lamin B2 and voltage
      dependent anion channel 2 have been reported to be involved in apoptosis.
      Treatment with styrene also caused the formation of styrene oxide-protein
      adducts, specifically for thioredoxin reductase 1. These results underline the
      relevance of oxidative stress as a primary molecular response mechanism of lung
      epithelial cells to styrene exposure at indoor-relevant concentrations.

PMID- 19862765
TI  - Effects of obesity induced by high-fat diet on the pharmacokinetics of
      nelfinavir, a HIV protease inhibitor, in laboratory rats.
AB  - The effect of obesity induced by a high-fat diet on the pharmacokinetics (PK) of
      nelfinavir (NFV) was investigated, focusing on the change of distribution and
      elimination caused by dyslipidemia and hepatic steatosis.The plasma unbound
      fraction (f(u)) of NFV in obese rats (0.61+/-0.03%) was significantly lower than
      in the control (1.10+/-0.09%), caused by increasing the plasma triglyceride-rich
      lipoprotein level. After intravenous (i.v.) administration of NFV, the marked
      decrease of the distribution volume and slower total clearance (39.5% and 69.1%
      of the control, respectively) caused by the lower f(u) were the main reasons for
      the significantly higher area under the blood concentration versus time curve
      (AUC) in obese rats (145.3% of the control). The absorption of NFV after
      intraduodenal (i.d.) administration in obese rats was significantly greater than
      in the control (AUC; 170.4% of the control). The increased bile in obese rats was
      the main reason for the increasing absorption of NFV, and the lower expression of
      intestinal P-glycoprotein was also considered. On the other hand, although higher
      AUCs in obese rats were shown, unbound AUCs in the obese rats were slightly lower
      than in the control, namely, the plasma NFV concentration in obese rats to obtain
      the same pharmacological effect was higher than in the control, suggesting the
      difficulty of drug monitoring. These results suggest that it is necessary to pay
      further attention to therapeutic drug monitoring of NFV in patients manifesting
      metabolic syndrome, such as dyslipidemia and visceral fat accumulation, including
      hepatic steatosis.

PMID- 19862766
TI  - Generation and dissociation of oxygen- and chloride-bridged iron(III) and
      manganese(III) tetraphenylporphyrin dimer ions in the gas phase.
AB  - Electrospray ionization mass spectrometry (ESI/MS) has allowed the discovery of
      novel dimer ions emerging from solutions of metalloporphyrin salts and their
      investigation by collision-induced dissociation (CID) with N(2) molecules. ESI
      mass spectra have been recorded for the formation of the oxygen or chloride
      bridged dimer ions [(FeTPP)(2)OH](+), [(MnTPP)(2)OH](+), [(FeTPP)(2)Cl](+) and
      [(MnTPP)(2)Cl](+) derived from various solutions of FeTPPCl and MnTPPCl salts.
      The CID of [(FeTPP)(2)OH](+) proceeds mainly by neutral loss of (FeTPP)OH to form
      [FeTPP](+) and, to a minor extent, to form the charge-reversed products. The CID
      of [(MnTPP)(2)OH](+) exhibits exclusively the product ion [MnTPP](+) by loss of
      neutral (MnTPP)OH. [(FeTPP)(2)Cl](+) and [(MnTPP)(2)Cl](+) dissociate by loss of
      (Fe/MnTPP)Cl to give rise to [Fe/MnTPP](+). [(FeTPP)(2)O](+) and
      [(FeTPP)(2)OH](+) were generated from a solution of the dimer, (FeTPP)(2)O.
      Dissociation of [(FeTPP)(2)O](+) yields two product ions, [FeTPP](+) and
      [(FeTPP)O](+), with higher onsets compared to the equivalent fragments formed
      from [(FeTPP)(2)OH](+).

PMID- 19862767
TI  - The Posttraumatic Growth Inventory: an examination of the factor structure and
      invariance among breast cancer survivors.
AB  - OBJECTIVE: The present study tested the proposed five-factor structure and
      invariance of the Posttraumatic Growth Inventory (PTGI; Tedeschi & Calhoun, 1996)
      in a sample of physically active breast cancer survivors. METHODS: A sample of
      breast cancer survivors (N=470, Mage=57.3, SD=7.8 years) completed the PTGI and a
      demographic questionnaire. The factor structure, factorial invariance, and latent
      mean invariance were tested using maximum likelihood structural equation
      modeling. RESULTS: Preliminary analyses showed acceptable reliability for the
      PTGI subscales (alpha<0.83). Confirmatory factor analysis (CFA) supported the
      five related factors corresponding to: relating to others, new possibilities,
      personal strength, spiritual change, and appreciation of life (chi(2)
      (179)=822.53, CFI=0.97, NNFI=0.96, SRMR=0.05, RMSEA=0.09). Multigroup CFA
      supported the invariance of the PTGI across age groups, treatment type, time
      since diagnosis, and time since last treatment. CONCLUSIONS: These findings
      provide support for (1) the multidimensional nature and factorial validity of the
      PTGI, and (2) the use of the PTGI in future research examining posttraumatic
      growth within samples of physically active breast cancer survivors.

PMID- 19862768
TI  - Pornography and attitudes supporting violence against women: revisiting the
      relationship in nonexperimental studies.
AB  - A meta-analysis was conducted to determine whether nonexperimental studies
      revealed an association between men's pornography consumption and their attitudes
      supporting violence against women. The meta-analysis corrected problems with a
      previously published meta-analysis and added more recent findings. In contrast to
      the earlier meta-analysis, the current results showed an overall significant
      positive association between pornography use and attitudes supporting violence
      against women in nonexperimental studies. In addition, such attitudes were found
      to correlate significantly higher with the use of sexually violent pornography
      than with the use of nonviolent pornography, although the latter relationship was
      also found to be significant. The study resolves what appeared to be a troubling
      discordance in the literature on pornography and aggressive attitudes by showing
      that the conclusions from nonexperimental studies in the area are in fact fully
      consistent with those of their counterpart experimental studies. This finding has
      important implications for the overall literature on pornography and aggression.

PMID- 19862769
TI  - Chinese women's preferences for prenatal diagnostic procedure and their
      willingness to trade between procedures.
AB  - OBJECTIVE: To assess Chinese women's preference for the choice of a prenatal
      diagnosis test, karyotyping or rapid aneuploidy, and its relationship to maternal
      psychological state. STUDY DESIGN: Three hundred consenting women completed a
      self administered structured questionnaire which documented their psychological
      state and their preferred choice of diagnostic test for chromosomal abnormality
      using a discrete choice experiment design. Diagnostic tests were categorised
      according to three attributes: completeness of chromosomal information, procedure
      to-result time interval and cost. RESULTS: Participants indicated a preference
      towards the karyotype test irrespective of cost and procedure-to-result time
      interval. The value of obtaining the extra information provided by karyotyping
      above that of rapid aneuploidy was pound267.82 (95% CI 226.71-323.31). Women
      would only accept the rapid aneuploidy test if results where available 18 days
      sooner than if they were undergoing a karyotyping test. Among women who traded
      between diagnostic tests, the value of extra chromosomal information was reduced
      to pound153.83 (95% CI 125.81-192.19). Women with high trait anxiety scores (>40)
      did not preferentially select one test. CONCLUSION: Chinese women showed a strong
      preference towards performing a full karyotype test and having a full chromosomal
      assessment performed for their pregnancy.

PMID- 19862770
TI  - Use of array comparative genomic hybridization for prenatal diagnosis of fetuses
      with sonographic anomalies and normal metaphase karyotype.
AB  - OBJECTIVE: To prospectively study the addition of array comparative genomic
      hybridization (CGH) to the prenatal evaluation of fetal structural anomalies.
      METHODS: Pregnant women carrying fetuses with a major structural abnormality were
      recruited at the time of invasive procedure for chromosome analysis. Only women
      whose fetuses had a normal karyotype (n = 50) were subsequently evaluated by
      array CGH using one of two arrays (1887 clones covering 622 loci or subsequently
      4685 clones covering 1500 loci). RESULTS: The mean gestational age of the fetuses
      was 24.5 weeks (range 11-38 weeks). The most prevalent anomalies were cardiac,
      central nervous system, skeletal, and urogenital. The median turnaround time for
      culturing and array CGH diagnosis was 18 days (range 2-72). Four of 50 fetuses
      had abnormal array results. One (2%) was clinically significant and three (6%)
      were inherited or benign variants. CONCLUSIONS: Array CGH studies in fetuses with
      sonographic anomalies and normal metaphase karyotype detected clinically
      significant copy number alterations in 1 of 50 cases. This percentage (2%) is
      consistent with prior prenatal reports. Further studies are warranted to more
      precisely identify which fetal anomalies are associated with copy number
      alterations of clinical significance.

PMID- 19862771
TI  - Impact of various food ingredients on the retention of furan in foods.
AB  - Since furan is classified as "possibly carcinogenic to humans," many studies
      investigated furan concentrations in foods. However, no data are available on the
      impact of food ingredients on the retention or release of furan from food. These
      data are important, since they explain the differences in furan removal during
      domestic food preparation. Furan retention was studied by spiking various samples
      with D(4)-furan and comparing D(4)-furan evaporation from these samples with
      comparable aqueous solutions. In addition, furan concentrations were determined.
      Furan retention caused by starch gels was negligible. Oils caused high furan
      retention: peak areas of furan in oils ranged from 22 to 25% of the corresponding
      aqueous solutions. In addition, in coffee, furan retention was mainly caused by
      the lipophilic fraction. However, since furan retention was also found in
      defatted coffee and coffee grounds, other coffee constituents also have the
      ability to retain furan. Peak areas of furan in the headspace of baby foods
      ranged from 71 to 97% of those in water. In addition, in this case, the highest
      retention was found in baby foods with added oils. Baby food containing spinach
      showed the highest furan concentration (172 ppb) as well as the highest furan
      retention.

PMID- 19862773
TI  - Oral administration of resveratrol in suppression of pulmonary metastasis of
      BALB/c mice challenged with CT26 colorectal adenocarcinoma cells.
AB  - Anti-cancer activities of resveratrol (3,4',5-trihydroxylstilbene) have attracted
      extensive research attention. Suppression of pulmonary metastasis of BALB/c mice
      challenged with CT26 colorectal adenocarcinoma cells achieved by oral
      administration of resveratrol was assessed in three separate experiments. Each
      mouse was challenged by tail vein injection with CT26 cells. Prior to challenge,
      8-wk-old mice were fed with a basal diet and orally administered with resveratrol
      (30 mg/kg/2 days) eight or twelve times. After challenge, oral administration of
      resveratrol was continued until mice were sacrificed on day 20. As integrated
      from three experiments, 3.7% of the control mice (n=27) and 68.7% of the
      resveratrol-treated mice (n=26) exhibited free of metastasis. In a second study,
      8-wk-old BALB/c mice were orally administered with resveratrol 12 times and
      challenged with CT26 cells for 100 days. All control mice died but 50% of the
      resveratrol-treated mice survived. The surviving mice were challenged with CT26
      cells by hypodermic injection, fed with a basal diet for an additional 30 days,
      and sacrificed. Tumor lumps or nodules were not detected at the injection sites
      or in the lungs. This reveals that intrinsic vaccination-like defense has
      resulted from administration of resveratrol and challenge of tumor cells.

PMID- 19862772
TI  - 3,3'-Dihydroxyisorenieratene prevents UV-induced formation of reactive oxygen
      species and the release of protein-bound zinc ions in human skin fibroblasts.
AB  - 3,3'-Dihydroxyisorenieratene (DHIR) is a structurally unusual carotenoid
      exhibiting bifunctional antioxidant properties. It is synthesized by
      Brevibacterium linens, used in dairy industry for the production of red smear
      cheeses. The compound protects cellular structures against photo-oxidative damage
      and inhibits the UV-dependent formation of thymidine dimers. Here we show that
      DHIR prevents a UV-induced intracellular release of zinc ions from proteins in
      human dermal fibroblasts. The effect is correlated with a decreased formation of
      intracellular reactive oxygen species. In contrast, zinc release from cellular
      proteins induced by hyperthermia is not affected by pretreatment of cells with
      the antioxidant DHIR. It is suggested that the intracellular zinc release upon UV
      irradiation is due to oxidative modifications of the zinc ligands in proteins
      (e.g. cysteine) and that protection by DHIR is due to intracellular scavenging of
      reactive oxygen species generated in photo-oxidation.

PMID- 19862775
TI  - Progression to impaired glucose metabolism in first-degree relatives of patients
      with type 2 diabetes in Isfahan, Iran.
AB  - BACKGROUND: The aim of this study was to estimate the progression rates from
      normal glucose tolerance (NGT) to impaired fasting glucose (IFG), impaired
      glucose tolerance (IGT) and diabetes, and from IFG and IGT to diabetes in first
      degree relatives (FDRs) of individuals with type 2 diabetes mellitus. METHODS: A
      total of 701 non-diabetic FDRs of consecutive patients with type 2 diabetes aged
      20-70 years in 2003-2005 were followed through 2007 for the occurrence of IGT,
      IFG and type 2 diabetes. Glucose tolerance classification was based on the
      criteria of the American Diabetes Association and standard 75 g 2-h oral glucose
      tolerance test (OGTT). RESULTS: The progression rate from NGT to IFG, IGT and
      diabetes were 8.6% (95% confidence interval (CI) 6.8-10.6), 3.7% (95% CI: 2.5
      5.1) and 0.5% (95% CI: 0.1-1.2) per year after an average of 27.6 months,
      respectively. Progression rates from IFG and IGT to diabetes were 5.1% (95% CI:
      2.1-10.2) and 9.9% (95% CI: 7.7-12.6) per year. CONCLUSIONS: To our knowledge,
      these are the first estimate of progression rates from NGT to IFG, IGT and
      diabetes in FDRs of individuals with type 2 diabetes in Iran. The progression
      rates to diabetes in these participants are high, and intensive follow-up and
      intervention strategies are recommended for these high-risk individuals.

PMID- 19862774
TI  - Triggering of DC migration by dengue virus stimulation of COX-2-dependent
      signaling cascades in vitro highlights the significance of these cascades beyond
      inflammation.
AB  - A term "bone-breaking fever" is used in Chinese medicine to describe the symptoms
      of patients infected with dengue virus (DV). We examined the significance of the
      COX-prostaglandin pathway in human DC infected by DV. We show that DV infection
      induced the expression of COX-2 and the production of prostaglandin E2 (PGE2) in
      DC, and stimulated the DNA binding of NF-kappaB and the kinase activity of both
      IkappaBalpha kinase (IKK) alpha and beta. DV infection also activated MAPK and AP
      1 signaling. Both IkappaBalpha kinase-NF-kappaB and MAPK-AP-1 were upstream of
      COX-2 activation. Our investigation into the significance of COX-2-PGE2 pathway
      also revealed that DV infection enhances DC migration by inducing CC chemokine
      receptor 7 (CCR7) expression, and that blocking COX-2 or MAPK activity suppresses
      DV-induced DC migration. Our data also suggest that PGE2 can induce CCR7
      expression on DC and that antagonists of the PGE2 receptors EP2 and EP4 suppress
      DV-induced DC migration. We further show that the increased CCR7 expression was
      observed in both DV-infected and bystander DC, suggesting the presence of
      secondary effects in inducing CCR7 expression. Collectively, this study reveals
      not only the pathways involved in COX-2 synthesis in DV-infected DC but also the
      autocrine action of PGE2 on the migration of DV-infected DC.

PMID- 19862777
TI  - Energetic costs of territorial boundary patrols by wild chimpanzees.
AB  - Chimpanzees are well known for their territorial behavior. Males who belong to
      the same community routinely patrol their territories, occasionally making deep
      incursions into those of their neighbors. Male chimpanzees may obtain several
      fitness benefits by participating in territorial boundary patrols, but patrolling
      is also likely to involve fitness costs. Patrollers risk injury or even death,
      and patrols may be energetically costly and may involve opportunity costs.
      Although territorial patrols have been reported at all long-term chimpanzee study
      sites, quantitative data on their energetic costs have not previously been
      available. I evaluated the energy costs of patrolling for male chimpanzees at
      Ngogo, Kibale National Park, Uganda during 14 months of observation. In 29
      patrols and matched control periods, I recorded the distances covered and time
      spent traveling and feeding by chimpanzees. I found that male chimpanzees covered
      longer distances, spent more time traveling, and spent less time feeding during
      patrols than during control periods. These results support the hypothesis that
      chimpanzees incur energetic costs while patrolling and suggest that ecological
      factors may constrain the ability of chimpanzees to patrol.

PMID- 19862776
TI  - Ion trap mass analysis at high pressure: an experimental characterization.
AB  - In recent years, it has become increasingly interesting to understand the
      performance of mass spectrometers at pressures much higher than those employed
      with conventional operating conditions. This interest has been driven by several
      influences, including demand for the development of reduced-power miniature mass
      spectrometers, desire for improved ion transfer into and through mass
      spectrometers, enhanced-yield preparative mass separations, and mass filtering at
      the atmospheric pressure interface. In this study, an instrument was configured
      to allow for the performance characterization of a rectilinear ion trap (RIT) at
      pressures up to 50 mtorr with air used as the buffer gas. The mass analysis
      efficiency, mass resolution, isolation efficiency, and collision-induced
      dissociation (CID) efficiency were evaluated at pressures ranging from 1 to 50
      mtorr. The extent of degradation of mass resolution, isolation efficiency and ion
      stability as functions of pressure were characterized. Also, the optimal
      resonance ejection conditions were obtained at various pressures. Operations at
      50 mtorr demonstrated improved CID efficiency in addition to peak widths of 2 and
      5 m/z units (full width at half-maximum, FWHM) for protonated caffeine (m/z 195)
      and Ultramark (m/z 1521) respectively.

PMID- 19862778
TI  - First trimester pregnancy associated plasma protein-A as a marker for poor
      pregnancy outcome in patients with early-onset fetal growth restriction.
AB  - OBJECTIVE: To determine whether pregnancy associated plasma protein-A (PAPP-A)
      can be used to identify pregnancies at risk for poor perinatal outcomes among
      patients with second trimester fetal growth restriction (FGR). METHODS: We
      analyzed outcomes for singleton pregnancies of patients with evidence of FGR in
      the second trimester who also had first trimester serum PAPP-A measured for
      aneuploidy risk assessment. We excluded pregnancies with aneuploidy, major
      anomalies, fetal infection, or second trimester premature rupture of membranes
      (PPROM). RESULTS: One hundred and ninety eight pregnancies with second trimester
      FGR and first trimester serum PAPP-A measurements were identified. PAPP-A below
      the fifth percentile was associated with an increased rate of third trimester SGA
      (50% vs 11%, p = 0.012), preterm birth (33.3% vs 8%, p = 0.039), NICU admission
      (33.3% vs 8%, p = 0.039), intrauterine or neonatal death (20% vs 0%, p = 0.002),
      smaller median birth weight (2975g vs 3085g, p = 0.026), and earlier median
      gestational age at delivery (38.14 weeks vs 39.86 weeks, p = 0.004). PAPP-A
      values below the 10th percentile and below the 25th percentile were also
      associated with poor outcomes. CONCLUSION: PAPP-A appears to be a useful marker
      for neonatal outcome in patients diagnosed with second trimester FGR.

PMID- 19862779
TI  - Ultra-deep hydrodesulfurization of diesel fuels on trimetallic NiMoW sulfide
      catalysts.

PMID- 19862780
TI  - OFF-ON fluorescent detection of thymidine nucleotides by a zinc(II)-cyclen
      complex bearing two diagonal pyrenes.

PMID- 19862782
TI  - Competing intermolecular interactions in the high-temperature solid phases of
      even saturated carboxylic acids (C10H19O2H to C20H39O2H).
AB  - Structural knowledge of the high-temperature phases of saturated carboxylic acids
      (C(n)H(2n-1)O(2)H) from C(6)H(11)O(2)H to C(23)H(45)O(2)H is now complete.
      Crystal structures of the high-temperature phases of even acids from decanoic
      (C(10)H(19)O(2)H) to eicosanoic (C(20)H(39)O(2)H) are reported. The crystal
      structures of the six compounds were determined from powder X-ray diffraction
      data following direct space methods and refined by the Rietveld method combined
      with force field geometry optimization. The combination proved to be a valuable
      approach to obtain structures that are chemically sensible and in close agreement
      with the powder pattern. At the end of the process solid-state DFT calculations
      were applied to improve the overall accuracy of the system but in this case DFT
      did not render better structures. The high-temperature solid phases of even
      carboxylic acids are all P2(1)/c with Z=4, the molecules are united into dimers
      via strong hydrogen bonds. Two major types of interactions govern the crystal
      packing of carboxylic acids, hydrogen bonds and van der Waals interactions. A
      survey of the intermolecular interactions has revealed that hydrogen bonds are
      the dominant interaction for acids with less than 23 carbon atoms in the alkyl
      chain while van der Waals interactions dominate the packing for acids with more
      than 23 carbon atoms.

PMID- 19862781
TI  - Glycosphingolipids--nature, function, and pharmacological modulation.
AB  - The discovery of the glycosphingolipids is generally attributed to Johan L. W.
      Thudichum, who in 1884 published on the chemical composition of the brain. In his
      studies he isolated several compounds from ethanolic brain extracts which he
      coined cerebrosides. He subjected one of these, phrenosin (now known as
      galactosylceramide), to acid hydrolysis, and this produced three distinct
      components. One he identified as a fatty acid and another proved to be an isomer
      of D-glucose, which is now known as D-galactose. The third component, with an
      "alkaloidal nature", presented "many enigmas" to Thudichum, and therefore he
      named it sphingosine, after the mythological riddle of the Sphinx. Today,
      sphingolipids and their glycosidated derivatives are the subjects of intense
      study aimed at elucidating their role in the structural integrity of the cell
      membrane, their participation in recognition and signaling events, and in
      particular their involvement in pathological processes that are at the basis of
      human disease (for example, sphingolipidoses and diabetes type 2). This Review
      details some of the recent findings on the biosynthesis, function, and
      degradation of glycosphingolipids in man, with a focus on the glycosphingolipid
      glucosylceramide. Special attention is paid to the clinical relevance of
      compounds directed at interfering with the factors responsible for
      glycosphingolipid metabolism.

PMID- 19862783
TI  - Ring-extended derivatives of gramicidin S with furanoid sugar amino acids in the
      turn region have enhanced antimicrobial activity.

PMID- 19862784
TI  - Transforming triglycerides and fatty acids into biofuels.
AB  - Fuels derived from biobased materials are attracting attention for their
      potential in securing the energy supply and protecting the environment. In this
      Minireview, we evaluate the use of biobased sources, particularly fatty acids and
      triglycerides from seed oils and animal fats, as fuels. The physical and chemical
      properties of these fatty acids and triglycerides are discussed, including the
      link to their sources and current availability to meet fuel demands. The current
      technologies, also known as the first-generation ones, for converting
      triglycerides into fuels are covered, including conventional methods such as
      transesterification, pyrolysis, cracking, and emulsions. Recent, second
      generation technological developments that lead to more commercially viable
      biofuels based on diesel-like hydrocarbons are also discussed.

PMID- 19862785
TI  - Chiral calcium catalysts with neutral coordinative ligands: enantioselective 1,4
      addition reactions of 1,3-dicarbonyl compounds to nitroalkenes.

PMID- 19862786
TI  - A gadolinium-bridged polytungstoarsenate(III) nanocluster:
      [Gd(8)As(12)W(124)O(432)(H(2)O)(22)](60-).

PMID- 19862787
TI  - Taming the silylium ion for low-temperature Diels-Alder reactions.

PMID- 19862789
TI  - A zero-emission fuel cell that uses carbonaceous colloids from biomass waste as
      fuel source.

PMID- 19862790
TI  - Potential enhancement of degradation of the nematicides aldicarb, oxamyl and
      fosthiazate in UK agricultural soils through repeated applications.
AB  - BACKGROUND: The potential for enhanced degradation of the carbamoyloxime
      nematicides aldicarb and oxamyl and the organophosphate fosthiazate was
      investigated in 35 UK agricultural soils. Under laboratory conditions, soil
      samples received three successive applications of nematicide at 25 day intervals.
      RESULTS: The second and third applications of aldicarb were degraded at a faster
      rate than the first application in six of the 15 aldicarb-treated soils, and a
      further three soils demonstrated rapid degradation of all three applications.
      High organic matter content and low pH had an inhibitory effect on the rate of
      aldicarb degradation. Rapid degradation was observed in nine out of the ten soils
      treated with oxamyl. In contrast, none of the fosthiazate-treated soils
      demonstrated enhanced degradation. CONCLUSION: The potential for enhanced
      degradation of aldicarb and oxamyl was demonstrated in nine out of 15 and nine
      out of ten soils respectively that had previously been treated with these active
      substances. Degradation of fosthiazate occurred at a much slower rate, with no
      evidence of enhanced degradation. Fosthiazate may provide a useful alternative in
      cases where the efficacy of aldicarb and oxamyl has been reduced as a result of
      enhanced degradation.

PMID- 19862791
TI  - Thanks for the memory.

PMID- 19862793
TI  - Catching Ips duplicatus (Sahlberg) (Coleoptera: Scolytidae) with pheromone-baited
      traps: optimal trap type, colour, height and distance to infestation.
AB  - BACKGROUND: Field trapping experiments were carried out to evaluate effective
      trap characteristics for maximising Ips duplicatus (Sahlberg) catches in
      pheromone-baited traps in China. RESULTS: Window-slot and cross-barrier traps had
      significantly higher catches than multiple-funnel traps. The colour of window
      slot traps showed a significant effect on catches, with dark colours (black and
      red) being more effective than light colours, especially white and yellow. Window
      slot traps at a 1.5-2.0 m level caught more beetles than those at either ground
      level (0-0.5 m) or at 3.5-4.0 m. Ips duplicatus can be attracted to pheromone
      baited traps over a distance of > 100 m from the forest edge in an open grassy
      field. There was a strong diurnal pattern of flight activity, with catches on
      window-slot traps occurring during the daytime with one broad peak at mid- to
      late afternoon. The seasonal flight activity of I. duplicatus as monitored by
      pheromone-baited window-slot traps during 2007-2008 indicated that three major
      flight peaks occurred in early June, late June-early July and late July
      respectively, suggesting the existence of a potential second generation.
      CONCLUSION: The optimal trap characteristics will improve the performance of
      pheromone-baited traps as a critical monitoring or mass-trapping tool to combat
      outbreaks of this pest species.

PMID- 19862794
TI  - Seasonal shifts in giant panda feeding behavior: relationships to bamboo plant
      part consumption.
AB  - The giant panda (Ailuropoda melanoleuca) is classified as a carnivore, yet
      subsists on a diet comprised almost exclusively of bamboo. Wild and captive giant
      pandas use highly selective foraging behaviors for processing and consuming
      bamboo. These behaviors are for the first time quantified in captive giant pandas
      over a 5-year period of time showing highly specific seasonal trends. Giant panda
      feeding behavior was recorded using live video observations of two giant pandas
      housed at the Memphis Zoo from November 2003 to June 2008. Leaf was the primary
      plant part consumed from June to December, whereas culm was consumed primarily
      from February to May, with both bears displaying similar seasonal shifts in plant
      part consumption. From May to June, leaf consumption increased significantly (P
      values<0.001); from June to August, leaf consumption remained high and stable.
      From December to March, leaf consumption decreased significantly (P
      values<0.001). Specific behaviors for bamboo leaf and culm consumption were also
      observed. Both bears formed wads of leaves before ingestion while feeding on
      leaf, but the male employed this feeding behavior more often than the female (54
      and 33%, respectively). Both bears used similar culm-stripping behavior (26 and
      25%), used to remove the outer layer and isolate the pith for consumption. This
      study indicates that unique seasonal foraging behaviors observed in wild pandas
      are also apparent in captive animals in relation to plant part selectivity and
      feeding behaviors.

PMID- 19862795
TI  - The impact of optimism on anxiety, depression and quality of life in urogenital
      cancer patients.
AB  - OBJECTIVE: The purpose of the present study was to examine the relationship
      between optimism and anxiety, depression and health-related quality of life
      (HRQOL). A further aim was to investigate the predictive value of optimism for
      anxiety, depression and HRQOL, quantified with and without controlling the
      corresponding base level. METHODS: A total of 427 urogenital cancer patients were
      asked to complete the Life Orientation Test (LOT), the Hospital Anxiety and
      Depression Scale (HADS) and the health survey SF-8 during their stay in the
      hospital (T1), two weeks later (T2) and three months later. RESULTS: Finally, 275
      patients (64.4%) completed all questionnaires. Optimism at T1 was significantly
      associated with anxiety (r=-0.35), depression (r=-0.41) and HRQOL (physical:
      r=0.29; mental: r=0.27) and can predict outcome variables three months later.
      After controlling for the base levels of anxiety, depression and HRQOL, the
      predictive value of optimism remained significant but small. The incrementally
      variance explained by the LOT varied between 2.1% in anxiety and 8.2% in physical
      HRQOL. CONCLUSION: Especially patients with a low level of optimism and a high
      level of pessimism are at risk for higher levels of anxiety and depression in
      addition to lowered HRQOL.

PMID- 19862796
TI  - Self-association promoted conformational transition of (3R,4S,8R,9R)-9-[(3,5
      bis(trifluoromethyl)phenyl))-thiourea](9-deoxy)-epi-cinchonine.
AB  - The conformational diversity of the (3R,4S,8R,9R)-9-[(3,5
      bis(trifluoromethyl)phenyl))-thiourea](9-deoxy)-epi-cinchonine organocatalyst is
      discussed. Low-temperature NMR experiments confirmed a self-association process,
      which promotes the quinoline rotation between two intramolecularly hydrogen
      bonded monomeric conformers of the catalyst. The balanced population of the
      coexisting monomeric and dimeric species allowed us to conduct a structural study
      of a rather complex conformational dynamics of the pure catalyst. The study is
      extended by a comparison with other members of the bifunctional amine-thiourea
      organocatalyst family. Changes in the molecular structure of the catalysts
      influence the interplay between intra- and intermolecular hydrogen bonding, and
      yield different extent of catalyst self-association. By assessing the
      conformation of the individual states, we established the thermodynamic model of
      a self-association promoted conformational transition.

PMID- 19862797
TI  - High-resolution 1H NMR spectroscopic investigation of a chick embryo model of
      neural tube development.
AB  - High-field (1)H nuclear magnetic resonance (NMR) spectroscopy together with
      cryogenic probe capabilities have been applied to obtain metabolic profiles of
      chick embryos and to determine the suitability of the platform for profiling such
      mass-limited samples. Metabolic profiles were generated for both pooled and
      single embryo samples at early stages of neural development, using both 600 and
      800 MHz (1)H NMR spectrometer platforms. High-resolution metabolic profiles,
      representing metabolites from many chemical classes, including triglycerides,
      organic acids, carbohydrates, amino acids and nucleosides, were rapidly acquired.
      Neural tube defects (NTDs) are severe congenital malformations, and evidence
      exists for prevention of NTDs by periconceptional supplementation of the diet
      with folate. The molecular basis for the protective ability of folate in
      prevention of NTDs is not clear, although the involvement of methylation has been
      postulated. Thus, the metabolic profiles of chick embryos following inhibition of
      enzymes of the methylation cycle and the effect of their action on neural tube
      closure were investigated. The embryos were profiled at early stages of
      development, and closure of the neural tube was followed via digital imaging.
      Metabolic profiles of embryo samples representing both neural tube closure and
      the neural tube remaining open were discriminated; glucose levels were found to
      be significantly higher in methylation-inhibited samples. The application of a
      non-targeted metabolic profiling approach for the study of a chick embryo model
      of NTDs is novel and presents the exciting potential to provide metabolic insight
      necessary to elucidate the complex interplay of one-carbon moiety metabolism and
      NTDs.

PMID- 19862798
TI  - Sequence determination of alphas1-casein isoforms from donkey by mass
      spectrometric methods.
AB  - Four co-eluting components, with experimentally measured M(r) of 23 658, 23 786,
      24 278 and 24 406 Da, were detected by reversed-phase high-performance liquid
      chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) analysis in the dephosphorylated casein
      fraction of a milk sample collected at middle lactation stage from an individual
      donkey belonging to the Ragusano breed. By coupling RP-HPLC, two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE), enzymatic digestions, MALDI-TOF MS
      and capillary RP-HPLC/nano-electrospray ionization tandem mass spectrometry (nESI
      MS/MS) analyses, the four components were identified as donkey's alpha(s1)-CNs
      and their sequences completely characterized, using the known mare's alpha(s1)-CN
      (GenBank Acc. No. AAK83668; M(r) 23750.7 Da) as reference. The proteins with M(r)
      of 23 786 and 23 658 Da differ in the presence of a glutamine residue at position
      83 in the full-length component and present the amino acid substitutions Q(8)-->H
      and H(115)-->Y with respect to the mare's alpha(s1)-CN. The other two components
      with M(r) 24 406 and 24 278 Da, which also differ in the presence of a glutamine
      residue at position 88 in the full-length component, show the insertion of the
      pentapeptide HTPRE between Leu(33) and the Glu(34). The two alpha(s1)-CNs bearing
      the pentapeptide insertion were named variants A (202 amino acids; M(r) 24 406)
      and A(1) (201 amino acids; M(r) 24 278), whereas the two alpha(s1)-CNs without
      the pentapeptide were named variants B (197 amino acids; M(r) 23 786) and B(1)
      (196 amino acids; M(r) 23 658).

PMID- 19862799
TI  - Effect of fracture gap on stability of compression plate fixation: a finite
      element study.
AB  - In compression plating, anatomical reduction and compression across the fracture
      site are the basic principles necessary to achieve primary bone healing. However,
      varying amounts of gap at the fracture site frequently occur due to technical
      pitfalls, such as overbending of the plate and inaccurate reduction, and due to
      the fracture configuration itself. Little is known as to how fracture gap affects
      stability of the bone-plate construct. We analyzed the effects of fracture gap
      size (1 and 4 mm) and bone defect (25%, 50%, 75%, 100%) on the biomechanical
      stability of the compression plate-bone construct through validated finite
      element analysis. The stiffnesses of eight different models were compared with
      the stiffness of an ideally compressed model (0 mm/0%). Stress concentration in
      form of peak von Mises stress (PVMS) was also evaluated. The decrease in
      stiffness depended mainly on the depth of bone defect. The decrease in stiffness
      was similar in models with the same defect and different gap size. Considerably
      more stress was concentrated around the central hole of the plate in gap models
      with the depth of bone defects of 75% and 100% than with smaller defects. We
      concluded that even a thin fracture gap (1 mm) with no contact between the
      fracture after plating decreases stiffness exponentially; contact at the fracture
      surfaces of > or =50% was necessary to avoid undue stress concentration in the
      plate.

PMID- 19862800
TI  - Nanostructure of collagen fibrils in human nucleus pulposus and its correlation
      with macroscale tissue mechanics.
AB  - Collagen fibrils are the main structural components of the nucleus pulposus
      tissue in the intervertebral discs. The structure-property relationship of the
      nucleus pulposus (NP) tissues is still unclear. We investigated the structure of
      individual collagen fibrils of the NP and evaluated its correlation with the bulk
      mechanical properties of the tissue. Collagen fibrils were extracted from the NP
      of discs retrieved from adolescents during scoliosis correction surgery, and the
      extracts were confirmed by SDS-PAGE. The diameters of the individual collagen
      fibrils were measured through atomic force microscopy, and the compressive
      mechanical properties of the tissues were evaluated by confined compression. The
      correlations between the nanoscale morphology of the collagen fibrils and the
      macroscale mechanical properties of the tissues were evaluated by linear
      regression. The SDS-PAGE results showed that the fibril extracts were largely
      composed of type II collagen. The mean diameter of the collagen fibrils was 92.1
      +/- 26.54 nm; the mean swelling pressure and compressive modulus of the tissues
      were 6.15 +/- 4.3 kPa and 1.23 +/- 0.7 MPa, respectively. The mean fibril
      diameter had no linear correlation (R(2) = 0.30) with the swelling pressure of
      the tissues. However, it had a mild linear correlation with the compressive
      modulus (p = 0.023, R(2) = 0.68). This is the first study, to our knowledge, to
      evaluate the nanostructure of the individual collagen fibrils of the nucleus
      pulposus and its relationship with macroscale mechanical properties of the NP
      tissues.

PMID- 19862801
TI  - Both nongenomic and genomic effects are involved in estradiol's enhancing the
      phenotype of smooth muscle cells in cultured prostate stromal cells.
AB  - BACKGROUND: Stromal smooth muscle cells (SMCs) play an important role in the
      pathogenesis and clinical symptom of benign prostatic hyperplasia. We had
      reported that estrogen enhances the phenotype of SMC in cultured prostate stromal
      cells (PRSCs). Here we further investigate the mechanism by which estrogen
      affects the differentiation of PRSCs. METHODS: Primary cultured PRSCs were
      stimulated with E2 or BSA-E2. The mRNA level of SMC-specific genes, smoothelin,
      and SM-MHC were measured by qRT-PCR. The SM-MHC protein was measured by Western
      blot. The mRNA and protein levels of TGF-beta1 were measured by qRT-PCR and
      ELISA. The MAPK inhibitor PD98059, the estrogen receptor antagonist ICI182,780
      and neutralizing antibody to TGF-beta1 were used to reveal the mechanism of
      estrogen effect. RESULTS: E2 and BSA-E2 significantly up-regulate the expression
      of SMC-specific genes in PRSCs. Both forms of estrogen could increase the
      expression of TGF-beta1, which can be blocked by pre-treating with PD98059.
      Moreover, PD98059 and TGF-beta1 neutralizing antibody could abrogate the effect
      of BSA-E2 on cell differentiation. However, they could only inhibit part of E2
      induced SMC phenotype enhancement. ICI182,780 could partially suppress the pro
      differentiation effect of E2 but had no influence on the effect of BSA-E2.
      Combined treatment with ICI182,780 and PD98059 can completely abrogate the effect
      of E2. CONCLUSIONS: Estrogen could promote the expression of TGF-beta1 in PRSCs
      through nongenomic activation of MAPK pathway, and in turn enhance the SMC
      phenotype. Besides for this nongenomic effect, estrogen can also enhance the SMC
      phenotype through classical genomic action.

PMID- 19862802
TI  - Feasibility study of pollen-shape drug carriers in dry powder inhalation.
AB  - The feasibility of using pollen-shape carriers in dry powder inhalation is
      studied. Pollen-shape hydroxyapatite (HA) particles are synthesized with a
      geometric diameter range from 21.1 to 48.6 microm and effective density range
      from 0.21 to 0.41 g/cm(3). The flowability of the particles is characterized by
      the Carr's compressibility index (CI) and angle of slide (theta). The HA carriers
      are found to have better flowability than commonly used lactose (LA) carrier with
      similar size range. The HA carriers are also found to be capable of high drug
      attachment. The aerosolization and deposition properties of a model drug are
      compared using HA and LA as carriers. Results indicate that pollen-shape HA
      carriers have good potential to be used as drug carrier in dry powder inhalation.
      It can give higher drug emission and respirable fraction than traditional LA
      carriers.

PMID- 19862803
TI  - Doubling the catabolic reducing power (NADH) output of Escherichia coli
      fermentation for production of reduced products.
AB  - Homofermentative production of reduced products requires additional reducing
      power output (NADH) from glucose catabolism. Anaerobic expression of the pyruvate
      dehydrogenase complex (PDH, encoded by aceEF-lpd, a normal aerobic operon) is
      able to provide the additional NADH required for production of reduced products
      in Escherichia coli fermentation. The multiple promoters (pflBp(1-7)) of pyruvate
      formate lyase (pflB) were evaluated for anaerobic expression of the aceEF-lpd
      operon. Four chromosomal constructs, pflBp(1-7)-aceEF-lpd, pflBp(1-6)-aceEF-lpd,
      pflBp(6,7)-aceEF-lpd, and pflBp6-aceEF-lpd efficiently expressed the PDH complex
      in anaerobically grown cells. Doubling the reducing power output was achieved
      when glucose was oxidized to acetyl-CoA through glycolysis and pyruvate oxidation
      by the anaerobically expressed PDH complex (glucose -->2 acetyl-CoA + 4 NADH).
      This additional reducing power output can be used for production of reduced
      products in anaerobic E. coli fermentation.

PMID- 19862804
TI  - Spray drying technique: II. Current applications in pharmaceutical technology.
AB  - This review presents current applications of spray drying in pharmaceutical
      technology. The topics discussed include the obtention of excipients and cospray
      dried composites, methods for increasing the aqueous solubility and
      bioavailability of active substances, and modified release profiles from spray
      dried particles. This review also describes the use of the spray drying technique
      in the context of biological therapies, such as the spray drying of proteins,
      inhalable powders, and viable organisms, and the modification of the physical
      properties of dry plant extracts.

PMID- 19862805
TI  - Economic analysis of angiography and preemptive angioplasty to prevent
      hemodialysis-access thrombosis.
AB  - OBJECTIVES: We sought to determine the economic value of early angiography and
      prophylactic angioplasty to prevent hemodialysis-access thrombosis. BACKGROUND:
      End stage renal disease consumes more than 6% of the Medicare budget. There is a
      need to understand the financial impact of each component of care. METHODS: We
      conducted an observational economic analysis of a closed cohort of 818
      hemodialysis patients, of whom 560 were referred for 1437 consecutive
      radiographic procedures during an 8-year period. Patient-level, bottom-up
      microcosting methods provided supply and personnel costs before and after
      expansion of an angiographic referral program. RESULTS: The rate of referral for
      malfunctioning but nonthrombosed hemodialysis accesses increased from 18.8 +/-
      8.8 to 48.3 +/- 11.9 angiographic procedures per 100 patient-years (P < 0.001),
      which was associated with a decline in access thrombosis from 27.6 to 22.0 events
      per 100 patient-years (P = 0.029) and a net cost of $34,586 per 100 patient
      years. The incremental cost-effectiveness ratio for invasive surveillance was
      $6,177 per thrombosis event avoided. The angiographic program expanded at the
      same time that the proportion of autogenous fistulas increased from 28.3% +/-
      11.3% to 59.7% +/- 10.7% of total referrals (P = 0.0001). On multivariable
      logistic regression analysis, the expanded angiography program (P = 0.001) and
      the proportion of autogenous fistulas (P = 0.0001) were both independently
      associated with the reduction in access thrombosis. CONCLUSIONS: Given the
      incremental costs and the relatively modest benefits in preventing access
      thrombosis, preemptive angiographic management may represent a less efficient use
      of healthcare resources than increasing the number of patients with autogenous
      fistulas. (c) 2009 Wiley-Liss, Inc.

PMID- 19862806
TI  - Covered Cheatham-Platinum stents for serial dilatation of severe native aortic
      coarctation.

PMID- 19862807
TI  - Isotopic evidence of dietary variations and weaning practices in the Gaya
      cemetery at Yeanri, Gimhae, South Korea.
AB  - Stable carbon and nitrogen isotope analyses were conducted to investigate dietary
      variation in human skeletons (n = 109) from the Gaya cemetery at Yeanri located
      near Gimhae City, South Korea. The cemetery contained three distinct grave types
      dating to 4th-7th century AD. The main purposes of this research were to
      reconstruct palaeodiet in the Gaya population and to explore correlations between
      stable isotope compositions and burial types, inferred age, and sex of these
      individuals. The isotopic data indicate that the people at Yeanri consumed a
      predominantly C(3)-based terrestrial diet supplemented with freshwater and/or
      marine resources. The comparison of isotopic results reveals significant
      differences in delta(13)C values among three adult burial types (wood-cist
      coffin: -18.5 +/- 0.5 per thousand, stone-cist coffin: -18.1 +/- 0.6 per
      thousand, mausoleum: -17.8 +/- 0.9 per thousand). Males in wood-cist and stone
      cist coffins have relatively more elevated mean delta(13)C and delta(15)N values
      than females. The isotopic ratios from the two adult age groups (21-40 years and
      40-60 years) indicate that there was no significant dietary change in individuals
      with age. The isotope data from the infants and children suggest the weaning was
      a gradual process that was completed between 3 and 4 years of age in the Gaya
      population. This evidence indicates that the dietary variations within the
      cemetery reflect social status, sex, and childhood consumption patterns.

PMID- 19862808
TI  - Blood group O alleles in Native Americans: implications in the peopling of the
      Americas.
AB  - All major ABO blood alleles are found in most populations worldwide, whereas the
      majority of Native Americans are nearly exclusively in the O group. O allele
      molecular characterization could aid in elucidating the possible causes of group
      O predominance in Native American populations. In this work, we studied exon 6
      and 7 sequence diversity in 180 O blood group individuals from four different
      Mesoamerican populations. Additionally, a comparative analysis of genetic
      diversity and population structure including South American populations was
      performed. Results revealed no significant differences among Mesoamerican and
      South American groups, but showed significant differences within population
      groups attributable to previously detected differences in genetic drift and
      founder effects throughout the American continent. Interestingly, in all American
      populations, the same set of haplotypes O(1), O(1v), and O(1v(G542A)) was
      present, suggesting the following: (1) that they constitute the main genetic pool
      of the founding population of the Americas and (2) that they derive from the same
      ancestral source, partially supporting the single founding population hypothesis.
      In addition, the consistent and restricted presence of the G542A mutation in
      Native Americans compared to worldwide populations allows it to be employed as an
      Ancestry informative marker (AIM). Present knowledge of the peopling of the
      Americas allows the prediction of the way in which the G542A mutation could have
      emerged in Beringia, probably during the differentiation process of Asian
      lineages that gave rise to the founding population of the continent.

PMID- 19862810
TI  - Theoretical and kinetic study of the H + C2H5CN reaction.
AB  - The reaction of H radical with C(2)H(5)CN has been studied using various quantum
      chemistry methods. The geometries were optimized at the B3LYP/6-311+G(d,p) and
      B3LYP/6-311++G(2d,2p) levels. The single-point energies were calculated using G3
      and BMC-CCSD methods based on B3LYP/6-311++G(2d,2p) geometries. Four mechanisms
      were investigated, namely, hydrogen abstraction, C-addition/elimination, N
      addition/elimination and substitution. The kinetics of this reaction were studied
      using the transition state theory and multichannel Rice-Ramsperger-Kassel-Marcus
      methodologies over a wide temperature range of 200-3000 K. The calculated results
      indicate that C-addition/elimination channel is the most feasible over the whole
      temperature range. The deactivation of initial adduct C(2)H(5)CHN is dominant at
      lower temperature with bath gas H(2) of 760 Torr; whereas C(2)H(5)+HCN is the
      dominant product at higher temperature. Our calculated rate constants are in good
      agreement with the available experimental data.

PMID- 19862809
TI  - Finger length ratios (2D:4D) in anthropoids implicate reduced prenatal androgens
      in social bonding.
AB  - The second-to-fourth digit ratio (2D:4D) has been proposed as a biomarker
      reflecting prenatal androgen effects (PAE), such that individuals with lower
      ratios have experienced higher PAE than those with higher ratios. 2D:4D has been
      correlated with a number of sex-linked traits in humans such as aggression,
      promiscuity, and competitiveness. In addition, polygynous societies reportedly
      have lower 2D:4D (higher PAE) than more monogamous populations. This evidence
      suggests that PAE may be implicated in the development of sexually selected
      behaviors in humans. To place 2D:4D research into a broader context, we test the
      relationship between digit ratios and behavior across nonhuman anthropoids;
      polygynous species, with higher levels of intrasexual competition, should have
      more pronounced markers of PAE (lower 2D:4D) than pair-bonded species. Our
      results accord with those found in humans: 2D:4D is lower in polygynous species
      and higher (lower PAE) in pair-bonded species. Old World monkeys have low, and
      relatively invariant 2D:4D (high PAE), which is coupled with high levels of
      intrasexual competition. This contrasts with higher and more variable ratios in
      both great apes and New World monkeys. In addition, both male and female ratios
      decrease with increasing levels of intrasexual competition. Human ratios are
      intermediate between pair-bonded and more promiscuous hominoids. We propose that
      PAE may be involved in promoting species characteristic social behavior in
      anthropoids.

PMID- 19862811
TI  - Computational design of protein-ligand binding: modifying the specificity of
      asparaginyl-tRNA synthetase.
AB  - A method for computational design of protein-ligand interactions is implemented
      and tested on the asparaginyl- and aspartyl-tRNA synthetase enzymes (AsnRS,
      AspRS). The substrate specificity of these enzymes is crucial for the accurate
      translation of the genetic code. The method relies on a molecular mechanics
      energy function and a simple, continuum electrostatic, implicit solvent model. As
      test calculations, we first compute AspRS-substrate binding free energy changes
      due to nine point mutations, for which experimental data are available; we also
      perform large-scale redesign of the entire active site of each enzyme (40 amino
      acids) and compare to experimental sequences. We then apply the method to
      engineer an increased binding of aspartyl-adenylate (AspAMP) into AsnRS. Mutants
      are obtained using several directed evolution protocols, where four or five amino
      acid positions in the active site are randomized. Promising mutants are subjected
      to molecular dynamics simulations; Poisson-Boltzmann calculations provide an
      estimate of the corresponding, AspAMP, binding free energy changes, relative to
      the native AsnRS. Several of the mutants are predicted to have an inverted
      binding specificity, preferring to bind AspAMP rather than the natural substrate,
      AsnAMP. The computed binding affinities are significantly weaker than the native,
      AsnRS:AsnAMP affinity, and in most cases, the active site structure is
      significantly changed, compared to the native complex. This almost certainly
      precludes catalytic activity. One of the designed sequences has a higher affinity
      and more native-like structure and may represent a valid candidate for Asp
      activity.

PMID- 19862812
TI  - Computational screening of biomolecular adsorption and self-assembly on nanoscale
      surfaces.
AB  - The quantification of binding properties of ions, surfactants, biopolymers, and
      other macromolecules to nanometer-scale surfaces is often difficult
      experimentally and a recurring challenge in molecular simulation. A simple and
      computationally efficient method is introduced to compute quantitatively the
      energy of adsorption of solute molecules on a given surface. Highly accurate
      summation of Coulomb energies as well as precise control of temperature and
      pressure is required to extract the small energy differences in complex
      environments characterized by a large total energy. The method involves the
      simulation of four systems, the surface-solute-solvent system, the solute-solvent
      system, the solvent system, and the surface-solvent system under consideration of
      equal molecular volumes of each component under NVT conditions using standard
      molecular dynamics or Monte Carlo algorithms. Particularly in chemically detailed
      systems including thousands of explicit solvent molecules and specific
      concentrations of ions and organic solutes, the method takes into account the
      effect of complex nonbond interactions and rotational isomeric states on the
      adsorption behavior on surfaces. As a numerical example, the adsorption of a
      dodecapeptide on the Au {111} and mica {001} surfaces is described in aqueous
      solution.

PMID- 19862813
TI  - Excited state properties, fluorescence energies, and lifetimes of a poly(fluorene
      phenylene), based on TD-DFT investigation.
AB  - The structural and electronic properties of fluorene-phenylene copolymer (FP)(n),
      n = 1-4 were studied by means of quantum chemical calculations based on density
      functional theory (DFT) and time dependent density functional theory (TD-DFT)
      using B3LYP functional. Geometry optimizations of these oligomers were performed
      for the ground state and the lowest singlet excited state. It was found that
      (FP)(n) is nonplanar in its ground state while the electronic excitations lead to
      planarity in its S(1) state. Absorption and fluorescence energies were calculated
      using TD-B3LYP/SVP and TD-B3LYP/SVP+ methods. Vertical excitation energies and
      fluorescence energies were obtained by extrapolating these values to infinite
      chain length, resulting in extrapolated values for vertical excitation energy of
      2.89 and 2.87 eV, respectively. The S(1) <-- S(0) electronic excitation is
      characterized as a highest occupied molecular orbital to lowest unoccupied
      molecular orbital transition and is distinguishing in terms of oscillator
      strength. Fluorescence energies of (FP)(n) calculated from TD-B3LYP/SVP and TD
      B3LYP/SVP+ methods are 2.27 and 2.26 eV, respectively. Radiative lifetimes are
      predicted to be 0.55 and 0.51 ns for TD-B3LYP/SVP and TD-B3LYP/SVP+ calculations,
      respectively. These fundamental information are valuable data in designing and
      making of promising materials for LED materials.

PMID- 19862814
TI  - Acute pulmonary failure during remission induction chemotherapy in adults with
      acute myeloid leukemia or high-risk myelodysplastic syndrome.
AB  - BACKGROUND: Acute pulmonary failure during remission induction therapy is a
      serious complication in patients with acute myeloid leukemia (AML). To the
      authors' knowledge, the course and prognosis of such patients is not well known.
      METHODS: A total of 1541 patients referred for remission induction chemotherapy
      of AML or high-risk myelodysplastic syndrome were retrospectively reviewed.
      RESULTS: A total of 120 (8%) patients developed acute pulmonary failure within 2
      weeks of the initiation of chemotherapy; 87 of these patients (73%) died during
      remission induction, whereas 17 (14%) achieved a complete response. The median
      survival among the 120 patients with early acute pulmonary failure was 3 weeks.
      Predictive factors for the development of early acute pulmonary failure by
      multivariate analysis were: male sex (P = .00038), acute promyelocytic leukemia
      (P = .00003), poor performance status (P = .001), lung infiltrates at diagnosis
      (P = .000001), and increased creatinine (P = .000005). Patients who had 0 to 1,
      2, 3, or 4 to 5 adverse factors were found to have estimated predictive
      incidences of acute pulmonary failure of 3%, 13%, 23%, and 34%, respectively.
      CONCLUSIONS: Preventive approaches at the start of induction therapy in patients
      at high risk of pulmonary failure may improve the outcome of these patients.

PMID- 19862815
TI  - Upfront, randomized, phase 2 trial of sorafenib versus sorafenib and low-dose
      interferon alfa in patients with advanced renal cell carcinoma: clinical and
      biomarker analysis.
AB  - BACKGROUND: The objective of this study was to independently evaluate the
      objective response rate of sorafenib and sorafenib plus low-dose interferon-alfa
      2b (IFN) as frontline therapy in patients with metastatic renal cell carcinoma
      (mRCC). METHODS: Untreated patients with clear cell mRCC were randomized to
      receive sorafenib 400 mg orally twice daily or sorafenib 400 mg orally twice
      daily plus subcutaneous IFN 0.5 million U (MU) twice daily. Primary endpoints
      included the objective response rate (ORR) and safety. Secondary endpoints
      included progression-free survival (PFS) and overall survival (OS). Exploratory
      endpoints included the predictive value of tumor tissue biomarkers. RESULTS:
      Eighty patients were enrolled. The median follow-up was 19.7 months (range, 0
      34.2 months). The ORR was 30% (95% confidence interval [CI], 16.6%-46.5%) in the
      sorafenib arm and 25% (95% CI, 12.7%-41.2%) in the combination arm. The median
      PFS was 7.39 months in the sorafenib-alone arm (95% CI, 5.52-9.20 months) and
      7.56 months in the sorafenib plus IFN arm (95% CI, 5.19-11.07 months). The median
      OS was 27.04 months in the combination arm (95% CI, from 22.31 to not attained)
      and was not reached in the sorafenib arm. Toxicities were comparable in both
      arms. In a multivariate model, increased phosphorylated protein kinase B (pAKT)
      levels were associated with poorer PFS (hazard ratio, 1.04; 95% CI, 1.00-1.08; P
      = .0411) and OS (hazard ratio, 1.15; 95% CI, 1.02-1.29; P = .0173). CONCLUSIONS:
      The addition of low-dose IFN to sorafenib resulted in efficacy outcomes that were
      comparable to those achieved with sorafenib monotherapy. The current results
      indicated that pAKT levels may predict for clinical outcome, but further
      mechanistic study is required.

PMID- 19862816
TI  - Extent of disease burden determined with magnetic resonance imaging of the bone
      marrow is predictive of survival outcome in patients with multiple myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) remains an incurable cancer. Treatment often is
      initiated at the time patients experience a progressive increase in tumor burden.
      The authors of this report investigated magnetic resonance imaging of the bone
      marrow (BM-MRI) as a novel approach to quantify disease burden and validated a
      staging system by correlating BM-MRI with common clinical and laboratory
      parameters. METHODS: The extent of bone marrow involvement was evaluated by BM
      MRI. Clinical and laboratory parameters were assessed in patients with active MM,
      and correlations between variables were assessed statistically. Bone marrow
      involvement by BM-MRI was defined as stage A (0%), stage B (<10%), stage C (10%
      50%), and stage D (>50%). RESULTS: In total, 170 consecutive patients were
      evaluated (77 women and 93 men), including 144 patients who had active MM. The
      median age was 61 years (age range, 35-83 years). Advance stage disease (stage
      >I) based on Durie-Salmon (DS) staging or International Staging System (ISS)
      criteria was observed in 122 patients (84%) and 77 patients (53%), respectively.
      Lytic bone disease was noted in 120 patients (83%). There was a significant
      association between BM-MRI involvement and DS stage (P = .0006), ISS stage (P =
      .0001), the presence of lytic bone disease (P < .0001) and mean beta-2
      microglobulin levels (P < .0001). Among the patients with previously untreated
      MM, there was a significant association between BM-MRI stage and overall survival
      (OS) (univariate P = .013; multivariate P = .045). Plasmacytosis on bone marrow
      biopsy at diagnosis was not predictive of OS (P = .91). CONCLUSIONS: BM-MRI is a
      novel approach for quantifying disease burden in patients with MM. The current
      investigation in a large cohort of nontransplantion MM patients demonstrated that
      the extent of bone marrow involvement determined by BM-MRI correlates accurately
      with other conventional parameters of disease burden and can independently
      predict survival in patients with MM at the time of initial diagnosis.

PMID- 19862817
TI  - Preliminary characterization of oral lesions associated with inhibitors of
      mammalian target of rapamycin in cancer patients.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as
      an intervention for advanced malignancies. Oral ulceration (OU), reported as
      mucositis, has been a dose-limiting toxicity for this new class of agents. An
      analysis of the appearance, course, and toxicity associations of mTOR inhibitor
      associated stomatitis (mIAS) demonstrated that the condition is distinct from
      conventional mucositis (CM) and more closely resembles aphthous stomatitis.
      METHODS: Safety data from 78 solid tumor patients enrolled in 2 Phase 1,
      multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK-8669) were
      evaluated. Adverse events (AEs) based on National Cancer Institute Common
      Toxicity Criteria for National Cancer Institute Common Terminology Criteria for
      Adverse Events (version 3.0) criteria were coded, consolidated, and stratified
      according to the presence or absence and duration of concordant OU. The relation
      between OU and other AEs was analyzed. RESULTS: Treatment-emergent AEs were
      reported in 91% of 78 study participants. OUs were reported in 66%, appeared
      within 5 days of deforolimus administration, and were discrete, ovoid,
      superficial, well demarcated, and surrounded by an erythematous halo. Their
      clinical appearance and distribution were similar to that of aphthous stomatitis
      but inconsistent with CM. Patients with OU were more likely to have nonspecific
      rashes and acneiform dermatitis but not gastrointestinal AEs. CONCLUSIONS: OU
      associated with mTOR inhibitor therapy differed from CM. Lesions more closely
      resembled those of aphthous stomatitis. The lack of other gastrointestinal
      involvement but the presence of a higher incidence of concomitant cutaneous AEs
      provided additional evidence to suggest a distinction between mIAS and CM.
      Treatment strategies for aphthous stomatitis may be a rational approach for the
      prevention and control of mIAS.

PMID- 19862819
TI  - The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients
      from a single institution.

PMID- 19862818
TI  - The symptom interval in children and adolescents with soft tissue sarcomas.
AB  - BACKGROUND: In a series of 575 patients < or =21 years of age with soft tissue
      sarcomas (STSs), the authors investigated the association patterns between
      symptom interval (ie, the period between the onset of the first symptoms or signs
      of the disease and its definitive diagnosis) and patient/tumor characteristics or
      disease outcome (in terms of survival). METHODS: The analysis was based on
      multivariate models (linear for associations with patient/tumor characteristics
      and Cox's for survival). RESULTS: The symptom interval ranged between 1 week and
      60 months (median, 2 months) and tended to be longer the older the patient (ie,
      the interval was longer in adolescents than in children) and the larger the
      tumor's size, and for tumors located at the extremities and for
      nonrhabdomyosarcoma STSs (as opposed to rhabdomyosarcomas). A longer symptom
      interval unfavorably influenced survival (P = .002), which was also significantly
      affected by the patient's age and the size and surgical stage of the tumor. A
      different pattern of association between symptom interval and survival emerged
      for different types of STS histology. CONCLUSIONS: Our study points to an
      independent prognostic effect of symptom interval that cannot be explained by its
      associations with other factors, such as patient's age or the site, size, stage,
      and histology of the tumor. Future studies should focus more on the possible
      causes of symptom interval in pediatric STS populations to enable corrective
      measures to be implemented to reduce the diagnostic delay.

PMID- 19862820
TI  - Results of a multicenter, randomized, double-blind phase 2/3 study of
      lenalidomide in the treatment of pretreated relapsed or refractory metastatic
      malignant melanoma.
AB  - BACKGROUND: The results of an international, multicenter, randomized, double
      blind, controlled study assessing the efficacy and safety of lenalidomide
      treatment in patients with refractory stage IV metastatic malignant melanoma are
      reported. METHODS: The study compared treatment with lenalidomide (25 mg/d on
      Days 1-21 of a 28-day cycle) to placebo in 306 patients with metastatic malignant
      melanoma. Treatment was continued until progression of disease or unacceptable
      toxicity. RESULTS: There were no significant differences between lenalidomide and
      placebo in overall survival (median 5.9 months vs 7.4 months, respectively; P =
      .32), time to progression (median 3.0 months vs 2.1 months; P = .19), or Response
      Evaluation Criteria in Solid Tumors tumor response (5.3% vs 5.8%; P = .82). None
      of the patients given placebo discontinued treatment because of treatment-related
      adverse events, compared with 4.6% of those treated with lenalidomide. Treatment
      related myelosuppression was observed in 2.0% of patients treated with placebo
      and 7.3% of patients treated with lenalidomide. CONCLUSIONS: This study showed
      that treatment with lenalidomide (25 mg/d) has a manageable safety profile in
      patients with previously treated metastatic malignant melanoma but no benefit in
      tumor response, time to progression, or overall survival in these patients.
      Future trials for treatment of metastatic malignant melanoma with lenalidomide
      should focus on its use in combination therapies.

PMID- 19862821
TI  - Hematopoietic immortalizing function of the NKL-subclass homeobox gene TLX1.
AB  - Translocations resulting in ectopic expression of the TLX1 homeobox gene
      (previously known as HOX11) are recurrent events in human T-cell acute
      lymphoblastic leukemia (T-ALL). Transduction of primary murine hematopoietic
      stem/progenitor cells with retroviral vectors expressing TLX1 readily yields
      immortalized hematopoietic progenitor cell lines. Understanding the processes
      involved in TLX1-mediated cellular immortalization should yield insights into the
      growth and differentiation pathways altered by TLX1 during the development of T
      ALL. In recent clinical gene therapy trials, hematopoietic clonal dominance or T
      ALL-like diseases have occurred as a direct consequence of insertional activation
      of the EVI1, PRDM16 or LMO2 proto-oncogenes by the retroviral vectors used to
      deliver the therapeutic genes. Additionally, the generation of murine
      hematopoietic progenitor cell lines due to retroviral integrations into Evi1 or
      Prdm16 has also been recently reported. Here, we determined by linker-mediated
      nested polymerase chain reaction the integration sites in eight TLX1-immortalized
      hematopoietic cell lines. Notably, no common integration site was observed among
      the cell lines. Moreover, no insertions into the Evi1 or Prdm16 genes were
      identified although insertion near Lmo2 was observed in one instance. However,
      neither Lmo2 nor any of the other genes examined surrounding the integration
      sites showed differential vector-influenced expression compared to the cell lines
      lacking such insertions. While we cannot exclude the possibility that insertional
      side effects transiently provided a selective growth/survival advantage to the
      hematopoietic progenitor populations, our results unequivocally rule out
      insertions into Evi1 and Prdm16 as being integral to the TLX1-initiated
      immortalization process.

PMID- 19862822
TI  - Frequent deletion of CDKN2A and recurrent coamplification of KIT, PDGFRA, and KDR
      in fibrosarcoma of bone--an array comparative genomic hybridization study.
AB  - Very little is known about the genetics of fibrosarcoma (FS) of bone. We applied
      array comparative genomic hybridization (CGH) to identify genes and genomic
      regions with potential role in the pathogenesis of this tumor. Seventeen patients
      with FS of bone were included in the study. Array CGH analysis was carried out in
      13 fresh frozen tissue specimens from 11 of these patients (nine primary tumors
      and four local recurrences). DNA was extracted and hybridizations were performed
      on Agilent 244K CGH oligoarrays. The data were analyzed using Agilent DNA
      Analytics Software. The number of changes per patient ranged from 0 to 132
      (average = 43). Losses were most commonly detected at 6q, 8p, 9p, 10, 13q, and
      20p. CDKN2A was homozygously deleted in 7/11 patients. Hypermethylation of both
      p16(INK4a) and p14(ARF) was found in 1/14 patients. An internal deletion of
      STARD13 was found in a region with common losses at 13q13.1. The most frequent
      gains were seen at 1q, 4q, 5p, 8q, 12p, 15q, 16q, 17q, 20q, 22q, and Xp. Single
      recurrent high level amplification was detected at 4q12, including KIT, PDGFRA,
      and KDR. No activating mutations were found in any of them. Immunohistochemistry
      revealed expression of PDGFRA and/or PDGFRB in 12/17 samples. Moreover, small
      regions of gains pinpointed genes of particular interest, such as IGF1R at
      15q26.3 and CHD1L at 1q21.1. In conclusion, our analysis provided novel findings
      that can be exploited when searching for markers for diagnosis and prognosis, and
      targets of therapy in this tumor type.

PMID- 19862823
TI  - Distinct MHC gene expression patterns during progression of melanoma.
AB  - Abnormal expression of major histocompatibility complex (MHC) molecules in
      melanoma has been reported previously. However, the MHC molecule expression
      patterns in different growth phases of melanoma and the underlying mechanisms are
      not well understood. Here, we demonstrate that in vertical growth phase (VGP)
      melanomas, MHC genes are subject to increased rates of DNA copy number gains,
      accompanied by increased expression, in comparison to normal melanocytes. In
      contrast, MHC expression in metastatic melanomas drastically decreased compared
      to VGP melanomas, despite still prevalent DNA copy number gains. Subsequent
      investigations found that the master transactivator of MHC genes, CIITA, was also
      significantly downregulated in metastatic melanomas when compared to VGP
      melanomas. This could be one of the mechanisms accounting for the discrepancy
      between DNA copy number and expression level in metastatic melanomas, a
      potentially separate mechanism of gene regulation. These results infer a dynamic
      role of MHC function in melanoma progression. We propose potential mechanisms for
      the overexpression of MHC molecules in earlier stages of melanoma as well as for
      its downregulation in metastatic melanomas.

PMID- 19862824
TI  - Comparison of biofilm formation on new Phonax and Provox 2 voice prostheses - a
      pilot study.
AB  - BACKGROUND: In voice rehabilitation for laryngectomized patients, voice
      prosthetic biofilm formation is still an unsolved problem. Design and materials
      of voice prostheses have been altered by manufacturers to improve function and
      extend the lifetime of devices. The goal of the study was to investigate biofilm
      formation on Provox 2 and Phonax, recently introduced voice prostheses made of
      thermoplastic polyurethane. METHODS: Five laryngectomized patients were equipped
      with both Phonax and Provox 2 voice prostheses. Microbial colonization was
      analyzed using standard microbiological methods. Biofilm formation and material
      infiltration were illustrated using scanning electron microscopy, fluorescence
      microscopy, and thin-section light microscopy. RESULTS: Although no differences
      in quality or quantity of microbial colonization were assessed, microscopic
      imaging revealed differences in material surfaces, biofilm composition, and
      infiltration morphologies; the polyurethane material seems to destabilize biofilm
      architecture by inhibition of hypheal Candida growth forms. CONCLUSIONS:
      Polyurethane material for voice prostheses seems to reduce biofilm stability and
      infiltrative processes.

PMID- 19862825
TI  - New insights in the vascular supply of the human parotid gland - consequences for
      parotid gland-sparing irradiation.
AB  - BACKGROUND: Xerostomia is caused by irradiation for head and neck cancer,
      depending on the dose to the parotid gland. To investigate which part of the
      parotid gland has to be spared with radiotherapy, detailed information about the
      vascular supply of the parotid gland is necessary. METHODS: Arterial vessels of
      the head of a human cadaver were colored. A 3-dimensional reconstruction of the
      parotid gland and the arterial vessels was made and analyzed. RESULTS: Five
      arterial vessels were responsible for the vascular supply of the parotid gland:
      the posterior auricular artery, 2 branches so far unnamed, the superficial
      temporal artery, and the transverse facial artery. All arteries were branches off
      the external carotid artery, and supplied different parts of the parotid gland.
      CONCLUSIONS: This study describes the detailed vascular supply of the human
      parotid gland. These results may contribute to improve parotid sparing
      radiotherapy, thus reducing complications such as xerostomia in the future.

PMID- 19862826
TI  - Retrospective comparison of mobilization methods for autologous stem cell
      transplantation in multiple myeloma.
AB  - The combination of cyclophosphamide and granulocyte-colony stimulating factor (G
      CSF) has widely been used to mobilize hematopoietic stem cells (HSCs) for
      autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Recently,
      however, alternative approaches such as G-CSF alone or etoposide followed by G
      CSF have been investigated. We, therefore, retrospectively analyzed the effects
      of these mobilization methods on collection yield and disease outcome in ASCT for
      MM. We reviewed 146 MM patients from whom we intended to collect stem cells. For
      mobilization, 67, 58, and 21 patients received cyclophosphamide and G-CSF,
      etoposide and G-CSF, and G-CSF alone (including nonmyelosuppressive chemotherapy
      followed by G-CSF), respectively. Among them, 136 achieved the target number of
      HSCs (at least 2 x 10(6)/kg). Lower creatinine and higher albumin levels at
      diagnosis were significantly associated with successful yield. A lower number of
      infused HSCs, use of the etoposide for mobilization and high ISS were associated
      with delayed hematopoietic recovery. The mobilization methods did not
      significantly affect either the successful collection of more than 2 x 10(6) CD34
      positive cells/kg or PFS after ASCT. G-CSF alone was sufficient for stem cell
      mobilization for a single ASCT. The optimal approach to collect HSCs in MM
      remains to be elucidated.

PMID- 19862827
TI  - Bisphosphonates-associated osteonecrosis of the jaw: A long-term follow-up of a
      series of 35 cases observed by GISL and evaluation of its frequency over time.

PMID- 19862828
TI  - Role of intratumoral lymphatic vessels in the lymph node dissemination of
      laryngopharyngeal squamous cell carcinoma.
AB  - BACKGROUND: The development of new markers for lymphatic endothelium allowed the
      study of intratumoral lymphatic microcirculation, as well as its association with
      lymph node metastasis. METHODS: In all, 120 patients with laryngopharyngeal
      squamous cell carcinoma (LPSCC) without previous treatment were retrospectively
      studied. The immunohistochemical determination of PA2.26 antigen/podoplanin was
      used to assess intratumoral lymphatic vessels (ILVs) in the primary tumor.
      RESULTS: Multivariate analysis revealed that lymph node metastasis was associated
      with tumor location (p = .001), differentiation grade (p = .02), and ILV (p =
      .013). Hypopharyngeal and supraglottic locations, poor grade of differentiation,
      and ILV, respectively, increased the risk of developing lymph node metastasis
      13.5-, 4.7-, 5.2-, and 3.2-fold. CONCLUSIONS: In our series, the presence of ILV
      in the primary tumor was an independent risk factor for the development of lymph
      node metastasis. The incorporation of ILV assessment into routine
      clinicopathological study might improve the evaluation of patients with LPSCC.

PMID- 19862829
TI  - Three-dimensional photogrammetry for surgical planning of tissue expansion in
      hemifacial microsomia.
AB  - BACKGROUND: We aim to illustrate the applications of 3-dimensional (3-D)
      photogrammetry for surgical planning and longitudinal assessment of the
      volumetric changes in hemifacial microsomia. METHODS: A 3-D photogrammetric
      system was employed for planning soft tissue expansion and transplantation of a
      vascularized scapular flap for a patient with hemifacial microsomia. The facial
      deficiency was calculated by superimposing a mirror of the normal side on the
      preoperative image. Postsurgical volumetric changes were monitored by serial
      superimposition of 3-D images. RESULTS: A total of 31 cm(3) of tissue expansion
      was achieved within a period of 4 weeks. A scapular free flap measuring 8 cm * 5
      cm was transplanted to augment the facial deficiency. Postsurgical shrinkage of
      the flap was observed mainly in the first 3 months and it was minimal thereafter.
      CONCLUSION: 3-D photogrammetry can be used as a noninvasive objective tool for
      assessing facial deformity, planning, and postoperative follow-up of surgical
      correction of facial asymmetry.

PMID- 19862830
TI  - Carcinoma arising from pharyngeal diverticula.
AB  - BACKGROUND: Pharyngeal diverticulum or Zenker's diverticulum carcinoma is a rare
      malignancy with a poor prognosis. Carcinoma arising in a recurrent pharyngeal
      diverticulum is even rarer, with only 1 such case reported in the English
      language literature. We report 2 patients with pharyngeal diverticulum carcinoma
      exhibiting an unusual presentation and good long-term, disease-free survival with
      normal speech and swallowing. METHODS: A 70-year-old man with a carcinoma in a
      recurrent pharyngeal diverticulum excised 20 years previously and a 65-year-old
      man with a neck mass as the only presentation of pharyngeal diverticulum
      carcinoma. RESULTS: Our patients were treated with open resection, laryngeal
      preservation, and postoperative radiotherapy (PORT), resulting in long-term tumor
      control and disease-free survival of 5 and 15 years (longest reported),
      respectively. CONCLUSION: One-stage diverticulectomy with or without radiotherapy
      is the treatment of choice and can provide long-term control and survival.

PMID- 19862831
TI  - When yellow jackets attack: recurrent and severe anaphylactic reactions to insect
      bites and stings.

PMID- 19862832
TI  - Selective amplification of mutant DNA: mutations come to light in melting DNA.

PMID- 19862833
TI  - The genetic basis of long QT and short QT syndromes: a mutation update.
AB  - Long QT and short QT syndromes (LQTS and SQTS) are cardiac repolarization
      abnormalities that are characterized by length perturbations of the QT interval
      as measured on electrocardiogram (ECG). Prolonged QT interval and a propensity
      for ventricular tachycardia of the torsades de pointes (TdP) type are
      characteristic of LQTS, while SQTS is characterized by shortened QT interval with
      tall peaked T-waves and a propensity for atrial fibrillation. Both syndromes
      represent a high risk for syncope and sudden death. LQTS exists as a congenital
      genetic disease (cLQTS) with more than 700 mutations described in 12 genes (LQT1
      12), but can also be acquired (aLQTS). The genetic forms of LQTS include Romano
      Ward syndrome (RWS), which is characterized by isolated LQTS and an autosomal
      dominant pattern of inheritance, and syndromes with LQTS in association with
      other conditions. The latter includes Jervell and Lange-Nielsen syndrome (JLNS),
      Andersen syndrome (AS), and Timothy syndrome (TS). The genetics are further
      complicated by the occurrence of double and triple heterozygotes in LQTS and a
      considerable number of nonpathogenic rare polymorphisms in the involved genes.
      SQTS is a very rare condition, caused by mutations in five genes (SQTS1-5). The
      present mutation update is a comprehensive description of all known LQTS- and
      SQTS-associated mutations.

PMID- 19862834
TI  - PINK1 mutations: does the dosage make the poison?

PMID- 19862835
TI  - Quantitative analysis of safranal in saffron extract and nanoparticle formulation
      by a validated high-performance thin-layer chromatographic method.
AB  - INTRODUCTION: Safranal is an effective anticonvulsant shown to act as an agonist
      at GABA(A) receptors. Nose to brain delivery via nanoparticle formulation might
      improve its brain delivery. A selective and sensitive analytical method is
      required for evaluation of safranal-based novel drug delivery systems. OBJECTIVE:
      To develop and validate a high-performance thin-layer chromatographic (HPTLC)
      method for the quantitative analysis of safranal as bulk, in saffron extract and
      in developed safranal-loaded nanoparticle formulation. METHODOLOGY:
      Chromatographic separation was achieved on silica gel pre-coated TLC aluminium
      plates 60F-254, using n-hexane:ethyl acetate (9 : 1, v/v) as the mobile phase.
      Quantitative analysis was carried out by densitometry at a wavelength of 310 nm.
      The method was validated and applied to detect related impurities, to analyse
      safranal in saffron extract and to evaluate safranal-loaded nanoparticles.
      RESULTS: Compact spots of safranal were observed at R(f) value 0.51 +/- 0.02. The
      method was linear (r = 0.9991) between 0.5 and 5.0 ng/spot. The intra- and inter
      day precisions were 1.08-2.17 and 1. 86-3.47%, respectively. The limit of
      detection was 50 ng/spot and the limit of quantification was 150 ng/spot. The
      method proved to be accurate (recovery 97.4-102.0%) and was selective for
      safranal. Evaluation of safranal-loaded nanoparticle formulation demonstrated
      drug loading of 23.0%, encapsulation efficiency of 42.0% and sustained drug
      release following biphasic pattern. CONCLUSION: The present method is useful for
      the quantitative and qualitative analysis of safranal and safranal-loaded
      nanoparticle formulation. It provides significant advantages in terms of greater
      specificity and rapid analysis.

PMID- 19862836
TI  - Vertebrae in compression: Mechanical behavior of arches and centra in the gray
      smooth-hound shark (Mustelus californicus).
AB  - In swimming sharks, vertebrae are subjected, in part, to compressive loads as
      axial muscles contract. We currently have no information about which vertebral
      elements, centra, arch cartilages, or both, actually bear compressive loads in
      cartilaginous vertebrae. To address this issue, the goal of this experiment was
      to determine the load-bearing ability of arch and centrum cartilages in
      compression, to determine the material properties of shark vertebrae, and to
      document fracture patterns in the centra with and without the arches. Intact
      vertebrae and vertebrae with the arch cartilages experimentally removed (centra
      alone) were subjected to compressive loading to failure at a single strain rate.
      The maximum compressive forces sustained by the vertebrae and the centra are
      statistically indistinguishable. Thus we conclude that under these testing
      conditions the arch does not bear appreciable loads. Independent evidence for
      this conclusion comes from the fact that vertebrae fail in compression at the
      centra, and not at the arches. Overall, the results of these mechanical tests
      suggest that the neural arches are not the primary load-bearing structure during
      axial compression.

PMID- 19862837
TI  - Abdominal muscle and epipubic bone function during locomotion in Australian
      possums: insights to basal mammalian conditions and Eutherian-like tendencies in
      Trichosurus.
AB  - Mammals have four hypaxial muscle layers that wrap around the abdomen between the
      pelvis, ribcage, and spine. However, the marsupials have epipubic bones extending
      anteriorly into the ventral hypaxial layers with two additional muscles extending
      to the ventral midline and femur. Comparisons of South American marsupials to
      basal eutherians have shown that all of the abdominal hypaxials are active
      bilaterally in resting ventilation. However, during locomotion marsupials employ
      an asymmetrical pattern of activity as the hypaxial muscles form a crosscouplet
      linkage that uses the epipubic bone as a lever to provide long-axis support of
      the body between diagonal limb couplets during each step. In basal eutherians,
      this system shifts off the femur and epipubic bones (which are lost) resulting in
      a shoulder to pelvis linkage associated with shifts in both the positions and
      activity patterns of the pectineus and rectus abdominis muscles during
      locomotion. In this study, we present data on hypaxial function in two species
      (Pseudocheirus peregrinus and Trichosurus vulpecula) representing the two major
      radiations of possums in Australia: the Pseudocheiridae (within the Petauroidea)
      and the Phalangeridae. Patterns of gait, motor activity, and morphology in these
      two Australian species were compared with previous work to examine the generality
      of 1) the crosscouplet lever system as the basal condition for the Marsupialia
      and 2) several traits hypothesized to be common to all mammals (hypaxial tonus
      during resting ventilation, ventilation to step synchrony during locomotion, and
      bilateral transversus abdominis activity during locomotor expiration). Our
      results validate the presence of the crosscouplet pattern and basic epipubic bone
      lever system in Australian possums and confirm the generality of basal mammalian
      patterns. However, several novelties discovered in Trichosurus, reveal that it
      exhibits an evolutionary transition to intermediate eutherian-like morphological
      and motor patterns paralleling many other unique features of this species.

PMID- 19862838
TI  - Ontogenetic change in skull morphology and mechanical advantage in the spotted
      hyena (Crocuta crocuta).
AB  - Weaning represents a challenging transition for young mammals, one particularly
      difficult for species coping with extreme conditions during feeding. Spotted
      hyenas (Crocuta crocuta) experience such extreme conditions imposed by intense
      feeding competition during which the ability to consume large quantities of food
      quickly is highly advantageous. As adult spotted hyenas have massive skulls
      specialized for durophagy and can feed very rapidly, young individuals are likely
      at a competitive disadvantage until that specialized morphology is completely
      developed. Here we document developmental changes in skull size, shape, and
      mechanical advantage of the jaws. Sampling an ontogenetic series of Crocuta
      skulls from individuals ranging in age from 2 months to 18 years, we use linear
      measurements and geometric morphometrics to test hypotheses suggesting that size,
      limited mechanical advantage of the jaws, and/or limited attachment sites for jaw
      muscles might constrain the feeding performance of juveniles. We also examine
      skull development in relation to key life history events, including weaning and
      reproductive maturity, to inquire whether ontogeny of the feeding apparatus is
      slower or more protracted in this species than in carnivores not specialized for
      durophagy. We find that, although mechanical advantage reaches maturity in hyenas
      at 22 months, adult skull size is not achieved until 29 months of age, and skull
      shape does not reach maturity until 35 months. The latter is nearly 2 years after
      mean weaning age, and more than 1 year after reproductive maturity. Thus, skull
      development in Crocuta is indeed protracted relative to that in most other
      carnivores. Based on the skull features that continue to change and to provide
      additional muscle attachment area, protracted development may be largely due to
      development of the massive musculature required by durophagy. These findings may
      ultimately shed light on the adaptive significance of the unusual "role-reversed"
      pattern of female dominance over males in this species.

PMID- 19862839
TI  - Lineage enforcement by inductive mesenchyme on adult epithelial stem cells across
      developmental germ layers.
AB  - During development, cell differentiation is accompanied by the progressive loss
      of pluripotent gene expression and developmental potential, although de
      differentiation in specialized cells can be induced by reprogramming strategies,
      indicating that transdifferentiation potential is retained in adult cells. The
      stromal niche provides differentiating cues to epithelial stem cells (SCs), but
      current evidence is restricted to tissue types within the same developmental germ
      layer lineage. Anticipating the use of adult SCs for tissue regeneration, we
      examined if stroma can enforce lineage commitment across germ layer boundaries
      and promote transdifferentiation of adult epithelial SCs. Here, we report tissue
      specific mesenchyme instructing epithelial cells from a different germ layer
      origin to express dual phenotypes. Prostatic stroma induced mammary epithelia (or
      enriched Lin(-)CD29(HI)CD24(+/MOD) mammary SCs) to generate glandular epithelia
      expressing both prostatic and mammary markers such as steroid hormone receptors
      and transcription factors including Foxa1, Nkx3.1, and GATA-3. Array data
      implicated Hh and Wnt pathways in mediating stromal-epithelial interactions
      (validated by increased Cyclin D1 expression). Other recombinants of prostatic
      mesenchyme and skin epithelia, or preputial gland mesenchyme and bladder or
      esophageal epithelia, showed foci expressing new markers adjacent to the original
      epithelial differentiation (e.g., sebaceous cells within bladder urothelium),
      confirming altered lineage specification induced by stroma and evidence of cross
      germ layer transdifferentiation. Thus, stromal cell niche is critical in
      maintaining (or redirecting) differentiation in adult epithelia. In order to use
      adult epithelial SCs in regenerative medicine, we must additionally regulate
      their intrinsic properties to prevent (or enable) transdifferentiation in
      specified SC niches.

PMID- 19862840
TI  - The effects of gender, family status, and race on sentencing decisions.
AB  - This study sought to determine the effects of family role, gender, and race on
      judges' sentencing decisions. To assess these effects, factorial surveys were
      sent to 360 Court of Common Plea judges who presided over criminal court cases in
      the state. Survey administration resulted in a 51% response rate. The findings
      indicate that defendants who were depicted as performing caretaker roles had a
      significantly decreased likelihood of incarceration. Further analysis found that
      the reduction in likelihood of incarceration for being a caretaker was larger for
      males than for females. Examination of the interaction of familial role with race
      found that familial role equally reduced the likelihood of incarceration for
      black and white females. Familial responsibility, however, resulted in a
      significantly greater decrease in likelihood of incarceration for black men than
      for white men.

PMID- 19862841
TI  - Pseudoexon exclusion by antisense therapy in methylmalonic aciduria (MMAuria).
AB  - Development of pseudoexon exclusion therapies by antisense modification of pre
      mRNA splicing represents a type of personalized genetic medicine. Here we present
      the cellular antisense therapy and the cell-based splicing assays to investigate
      the effect of two novel deep intronic changes c.1957-898A>G and c.1957-920C>A
      identified in the methylmalonyl-coenzyme A (CoA) mutase (MUT) gene. The results
      show that the nucleotide change c.1957-898A>G is a pathological mutation
      activating pseudoexon insertion and that antisense morpholino oligonucleotide
      (AMO) treatment in patient fibroblasts leads to recovery of MUT activity to
      levels 25 to 100% of control range. On the contrary, the change c.1957-920C>A,
      identified in two fibroblasts cell lines in cis with c.1885A>G (p.R629G) or
      c.458T>A (p.D153V), appears to be a rare variant of uncertain clinical
      significance. The functional analysis of c.1885A>G and c.458T>A indicate that
      they are the disease-causing mutations in these two patients. The results
      presented here highlight the necessity of scanning the described intronic region
      for mutations in MUT-affected patients, followed by functional analyses to
      demonstrate the pathogenicity of the identified changes, and extend previous work
      of the applicability of the antisense approach in methylmalonic aciduria
      (MMAuria) for a novel intronic mutation.

PMID- 19862843
TI  - The pharmacological chaperone 1-deoxynojirimycin increases the activity and
      lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase.
AB  - Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the
      gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule
      pharmacological chaperones have been shown to increase protein stability and
      cellular levels for mutant lysosomal enzymes and have emerged as a new
      therapeutic strategy for the treatment of LSDs. In this study, we characterized
      the pharmacological chaperone 1-deoxynojirimycin (DNJ) on 76 different mutant
      forms of GAA identified in Pompe disease. DNJ significantly increased enzyme
      activity and protein levels for 16 different GAA mutants in patient-derived
      fibroblasts and in transiently transfected COS-7 cells. Additionally, DNJ
      increased the processing of these GAA mutants to their mature lysosomal forms,
      suggesting facilitated trafficking through the secretory pathway.
      Immunofluorescence microscopy studies showed increased colocalization of GAA with
      the lysosomal marker LAMP2 after incubation with DNJ, confirming increased
      lysosomal trafficking. Lastly, a GAA structural model was constructed based on
      the related eukaryotic glucosidase maltase-glucoamylase. The mutated residues
      identified in responsive forms of GAA are located throughout most of the
      structural domains, with half of these residues located in two short regions
      within the catalytic domain. Taken together, these data support further
      evaluation of DNJ as a potential treatment for Pompe disease in patients that
      express responsive forms of GAA.

PMID- 19862844
TI  - Congenital disorders of glycosylation: an update on defects affecting the
      biosynthesis of dolichol-linked oligosaccharides.
AB  - Defects in the biosynthesis of the oligosaccharide precursor for N-glycosylation
      lead to decreased occupancy of glycosylation sites and thereby to diseases known
      as congenital disorders of glycosylation (CDG). In the last 20 years,
      approximately 1,000 CDG patients have been identified presenting with multiple
      organ dysfunctions. This review sets the state of the art by listing all
      mutations identified in the 15 genes (PMM2, MPI, DPAGT1, ALG1, ALG2, ALG3, ALG9,
      ALG12, ALG6, ALG8, DOLK, DPM1, DPM3, MPDU1, and RFT1) that yield a deficiency of
      dolichol-linked oligosaccharide biosynthesis. The present analysis shows that
      most mutations lead to substitutions of strongly conserved amino acid residues
      across eukaryotes. Furthermore, the comparison between the different forms of CDG
      affecting dolichol-linked oligosaccharide biosynthesis shows that the severity of
      the disease does not relate to the position of the mutated gene along this
      biosynthetic pathway.

PMID- 19862845
TI  - Peptide T exhibits a well-defined structure in fluorinated solvent at low
      temperature.
AB  - The structure of Peptide T was determined by solution NMR spectroscopy, under
      strong structure-inducing conditions: 40% hexafluoro-2-propanol aqueous solution
      at 5 degrees C. Under these conditions it was possible to detect medium-range
      NOEs for the first time for this peptide. This allowed a much better-defined
      structure to be determined for Peptide T in comparison with earlier NMR and
      computational studies. Peptide structures consistent with the experimental
      restraints were generated using a restrained MD simulation with a full empirical
      force field. Residues 4-8 of Peptide T take on a well-defined structure with a
      heavy atom RMSD of 0.78 A. The structure is stabilized by hydrogen bonding to
      side-chain oxygen atoms of Thr 4 and Thr 8, as well as backbone hydrogen bonding
      between residues 5 and 7 that forms this region into a classic gamma-turn.

PMID- 19862846
TI  - Ethics of modern developments in agriculture technologies. Opinion No. 24 of the
      European Group of Ethics in Science and New Technologies to the European
      Commission.

PMID- 19862842
TI  - Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria.
AB  - Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder,
      characterized by accumulation of homogentisic acid, leading to darkened urine,
      pigmentation of connective tissue (ochronosis), joint and spine arthritis, and
      destruction of cardiac valves. AKU is due to mutations in the homogentisate
      dioxygenase gene (HGD) that converts homogentisic acid to maleylacetoacetic acid
      in the tyrosine catabolic pathway. Here we report a comprehensive mutation
      analysis of 93 patients enrolled in our study, as well as an extensive update of
      all previously published HGD mutations associated with AKU. Within our patient
      cohort, we identified 52 HGD variants, of which 22 were novel. This yields a
      total of 91 identified HGD variations associated with AKU to date, including 62
      missense, 13 splice site, 10 frameshift, 5 nonsense, and 1 no-stop mutation. Most
      HGD variants reside in exons 3, 6, 8, and 13. We assessed the potential effect of
      all missense variations on protein function, using five bioinformatic tools
      specifically designed for interpretation of missense variants (SIFT, POLYPHEN,
      PANTHER, PMUT, and SNAP). We also analyzed the potential effect of splice-site
      variants using two different tools (BDGP and NetGene2). This study provides
      valuable resources for molecular analysis of alkaptonuria and expands our
      knowledge of the molecular basis of this disease.

PMID- 19862847
TI  - Position of the American Dietetic Association: promoting and supporting
      breastfeeding.
AB  - It is the position of the American Dietetic Association that exclusive
      breastfeeding provides optimal nutrition and health protection for the first 6
      months of life and breastfeeding with complementary foods from 6 months until at
      least 12 months of age is the ideal feeding pattern for infants. Breastfeeding is
      an important public health strategy for improving infant and child morbidity and
      mortality, improving maternal morbidity, and helping to control health care
      costs. Breastfeeding is associated with a reduced risk of otitis media,
      gastroenteritis, respiratory illness,sudden infant death syndrome,necrotizing
      enterocolitis, obesity, and hypertension. Breastfeeding is also associated with
      improved maternal outcomes, including a reduced risk of breast and ovarian
      cancer, type 2 diabetes, and postpartum depression.These reductions in acute and
      chronic illness help to decrease health care-related expenses and productive time
      lost from work. Overall breastfeeding rates are increasing, yet disparities
      persist based on socioeconomic status, maternal age, country of origin,and
      geographic location. Factors such as hospital practices, knowledge, beliefs, and
      attitudes of mothers and their families, and access to breastfeeding support can
      influence initiation, duration, and exclusivity of breastfeeding. As experts in
      food and nutrition throughout the life cycle, it is the responsibility of
      registered dietitians and dietetic technicians, registered, to promote and
      support breastfeeding for its short-term and long-term health benefits for both
      mothers and infants.

PMID- 19862848
TI  - Microarrays: indirect CyDye labeling.

PMID- 19862849
TI  - Improved PCR specificity with Hot Start PCR primers.

PMID- 19862850
TI  - Achieving success in higher education.

PMID- 19862851
TI  - Open lung biopsy in patients on mechanical ventilation with suspected diffuse
      lung disease.

PMID- 19862853
TI  - [Novel findings in functions of TRP channel protein and pathophysiology].

PMID- 19862854
TI  - Laser surgery: go in with your eyes open.

PMID- 19862855
TI  - Health-care reform: behind the ads.

PMID- 19862856
TI  - Doctors, admit your mistakes.

PMID- 19862857
TI  - Sources of health insurance and characteristics of the uninsured: analysis of the
      March 2009 Current Population Survey.
AB  - This Issue Brief provides historical data through 2008 on the number and
      percentage of nonelderly individuals with and without health insurance. Based on
      EBRI estimates from the U.S. Census Bureau's March 2009 Current Population Survey
      (CPS), it reflects 2008 data. It also discusses trends in coverage for the 1994
      2008 period and highlights characteristics that typically indicate whether an
      individual is insured. HEALTH COVERAGE RATE CONTINUES TO DECREASE: The percentage
      of the nonelderly population (under age 65) with health insurance coverage
      decreased to 82.6 percent in 2008. Increases in health insurance coverage have
      been recorded in only four years since 1994, when 36.5 million nonelderly
      individuals were uninsured; in 2008, the uninsured population was 45.7 million.
      EMPLOYMENT-BASED COVERAGE REMAINS DOMINANT SOURCE OF HEALTH COVERAGE, BUT
      CONTINUES TO SLOWLY ERODE: Employment-based health benefits remain the most
      common form of health coverage in the United States. In 2008, 61.1 percent of the
      nonelderly population had employment-based health benefits, down from 68.4
      percent in 2000. Between 1994 and 2000, the percentage of the nonelderly
      population with employment-based coverage expanded. PUBLIC PROGRAM COVERAGE IS
      GROWING: Public program health coverage expanded as a percentage of the
      population in 2008, accounting for 19.4 percent of the nonelderly population.
      Enrollment in Medicaid and the State Children's Health Insurance Program
      increased, reaching a combined 39.2 million in 2008, and covering 14.9 percent of
      the nonelderly population, significantly above the 10.5 percent level of 1999.
      INDIVIDUAL COVERAGE STABLE: Individually purchased health coverage was unchanged
      in 2008 and has basically hovered in the 6-7 percent range since 1994. MOST/LEAST
      LIKELY TO HAVE HEALTH INSURANCE: Full-time, full-year workers, public-sector
      workers, workers employed in manufacturing, managerial and professional workers,
      and individuals living in high-income families are most likely to have employment
      based health benefits. Poor families are most likely to be covered by public
      coverage programs such as Medicaid or S-CHIP. RETHINKING THE VALUE OF OFFERING
      HEALTH INSURANCE: Research illustrates the advantages to consumers of having
      health insurance and the benefits to employers of offering it. In general, the
      availability of health insurance allows consumers to avoid unnecessary pain and
      suffering and improves the quality of life, and employers report that offering
      benefits has a positive impact on worker recruitment, retention, health status,
      and productivity. Employers may believe in the business case for providing health
      benefits today, but in the future they may rethink the value that offering
      coverage provides, especially if health costs continue to escalate sharply or if
      health reform changes the value proposition.

PMID- 19862852
TI  - Association study of DTNBP1 with schizophrenia  in a US sample.
AB  - BACKGROUND: Straub et al. (2002b) located a susceptibility region for
      schizophrenia at the DTNBP1 locus. At least 40 studies (including one study in US
      populations) attempted to replicate this original finding, but the reported
      findings are highly diverse and at least five pathways by which dysbindin protein
      might be involved in schizophrenia have been proposed. This study aimed to test
      the association in two common US populations by using powerful analytic methods.
      METHODS: Six markers at DTNBP1 were genotyped by mass spectroscopy ('MassARRAY'
      technique) in a sample of 663 individuals, including 346 healthy individuals
      European-Americans (EAs) and 48 African-Americans (AAs), and 317 individuals with
      schizophrenia (235 EAs and 82 AAs). Thirty-eight ancestry-informative markers
      were genotyped in this sample to infer the ancestry proportions. Diplotype,
      haplotype, genotype, and allele frequency distributions were compared between the
      cases and controls, controlling for possible population stratification,
      admixture, and sex-specific effects, and taking interaction effects into account,
      using a logistic regression analysis (an extended structured association method).
      RESULTS: Conventional case-control comparisons showed that genotypes of the
      markers P1578 (rs1018381) and P1583 (rs909706) were nominally associated with
      schizophrenia in EAs and in AAs, respectively. These associations became less or
      nonsignificant after controlling for population stratification and admixture
      effects (using structured association or regression analysis), and became
      nonsignificant after correction for multiple testing. However, regression
      analysis showed that the common diplotypes (ACCCTT/GCCGCC or GCCGCC/GCCGCC) and
      the interaction effects of haplotypes GCCGCC/GCCGCC significantly affected risk
      for schizophrenia in EAs, effects that were modified by sex. Fine-mapping using d
      or J statistics located the specific markers (d: P1328; J: P1333) closest to the
      putative risk sites in EAs. CONCLUSION: This study shows that DTNBP1 is a risk
      gene for schizophrenia in EAs. Variation at DTNBP1 may modify risk for
      schizophrenia in this population.

PMID- 19862858
TI  - GHA honors longtime CEO John Bowling, FACHE as 2009 Chairman's Award winner.

PMID- 19862859
TI  - A call for action.

PMID- 19862860
TI  - PHA's reliable system initiative making care better, safer.

PMID- 19862861
TI  - American Recovery and Reinvestment Act: making hospitals technologically
      advanced.

PMID- 19862862
TI  - A voice of reason in the health care reform debate.

PMID- 19862863
TI  - Modelling a radiology department service using a VDL integrated approach.
AB  - PURPOSE: The healthcare industry is facing several challenges such as the
      reduction of costs and quality improvement of the provided services. Engineering
      studies could be very useful in supporting organizational and management
      processes. Healthcare service efficiency depends on a strong collaboration
      between clinical and engineering experts, especially when it comes to analyzing
      the system and its constraints in detail and subsequently, when it comes to
      deciding on the reengineering of some key activities. The purpose of this paper
      is to propose a case study showing how a mix of representation tools allow a
      manager of a radiology department to solve some human and technological resource
      re-organizational issues, which have to be faced due to the introduction of a new
      technology and a new portfolio of services. DESIGN/METHODOLOGY/APPROACH: In order
      to simulate the activities within the radiology department and examine the
      relationship between human and technological resources, different visual
      diagrammatic language (VDL) techniques have been implemented to get knowledge
      about the heterogeneous factors related to the healthcare service delivery. In
      particular, flow charts, IDEFO diagrams and Petri nets have been integrated each
      other with success as a modelisation tools. FINDINGS: The simulation study
      performed through the application of the aforementioned VDL techniques suggests
      the opportunity of re-organizing the nurse activities within the radiology
      department. ORIGINALITY/VALUE: The re-organization of a healthcare service and in
      particular of a radiology department by means of joint flow charts, IDEF0
      diagrams and Petri nets is a poorly investigated topic in literature. This paper
      demonstrates how flow charts and IDEF0 can help people working within the
      department to understand the weak points of their organization and constitute an
      efficient base of knowledge for the implementation of a Petri net aimed at
      improving the departmental performance.

PMID- 19862864
TI  - Unitary management, multiple practices?
AB  - PURPOSE: The purpose of this paper is to explore whether unitary managers with
      different professional backgrounds carry out and reflect differently upon their
      roles as unitary managers. DESIGN/METHODOLOGY/APPROACH: This paper presents
      findings from two different studies, comprising both data from qualitative
      interviews and a nationwide survey. FINDINGS: Doctors and nurses in many respects
      perform their roles as unitary managers differently. They hold the same position
      but carry out their roles differently. Doctors are very committed to clinical
      tasks and stress to a great extent that clinical tasks should be integrated in
      management at the department level. The opposite is true for the nurses, where
      leadership first and foremost should be understood as management. PRACTICAL
      IMPLICATIONS: Even though doctors and nurses are in the same position they manage
      differently, being committed to different tasks within the unit. This is not the
      intention of the reform. However, the question is thus, will this have (severe)
      consequences for the organization? Or does it represent a healthy diversity in
      the health organisation? ORIGINALITY/VALUE: This paper explores whether different
      professions carry out their managerial tasks differently and what practical
      implications this could have. It brings to the fore substantial empirical data on
      how one of the major reforms in Norwegian (and international) health care has
      been adopted and carried out by major professional groups.

PMID- 19862865
TI  - Contemporary leadership in healthcare organizations: fragmented or concurrent
      leadership.
AB  - PURPOSE: The purpose of this paper is to gain a deeper understanding of the main
      contemporary challenges for healthcare leaders in their everyday work practice,
      and the support they need to master their experienced dilemmas.
      DESIGN/METHODOLOGY/APPROACH: Qualitative in-depth interviews (n=52), and focus
      group interviews (n=6) with 31 first-line and 45 second-line healthcare leaders
      are analysed in line with constructivist grounded theory. FINDINGS: In this
      paper, two leadership models are proposed for defining and differentiating ways
      of meeting different logics and demands made on leaders in the healthcare sector.
      The first model is leadership by separating different logics and fragmentation of
      time. Here, leaders express a desire for support in defining, structuring,
      dividing, and allocating tasks. The second model is leadership by integrating
      different logics and currentness of solutions. In this case, leaders want support
      in strengthening proactive leadership and shaping the basis for participative
      employeeship. RESEARCH LIMITATIONS/IMPLICATIONS: This research is designed to
      describe what people experience rather than to assess the frequency of that
      experience in the studied settings. However, it would be interesting to elaborate
      on the findings of this study using other research methodologies. PRACTICAL
      IMPLICATIONS: The findings contribute to contextual knowledge that is of
      relevance in supporting healthcare leaders. This is helpful in identifying
      important conditions that support the establishment of leadership and
      employeeship, leading to improvements in healthcare practice. ORIGINALITY/VALUE:
      The paper describes how contemporary leadership in the healthcare sector is
      constituted through different strategies for meeting multiple logics.

PMID- 19862866
TI  - Measurement of social capital as an indicator of community-based initiatives
      (CBI) in the Islamic Republic of Iran.
AB  - PURPOSE: The purpose of this paper is to observe whether measurement of social
      capital is an effective tool or can be used as a standard tool for community
      based initiatives (CBI) evaluation. It also points at the significance of social
      capital in the health related grass root initiatives.
      DESIGN/METHODOLOGY/APPROACH: CBI is an integrated socio-economic development
      approach implemented by the organized communities, supported by inter-sectoral
      actions for improvement of quality of life and health of the people. Support by
      WHO's office of Eastern Mediterranean Region, Islamic Republic of Iran implement
      programmes like basic development needs, healthy cities, healthy villages and
      women in health and development, that are evaluated during 2005-2006. Social
      capital, that includes the networking, sharing norms and cooperation amongst
      communities, is measured as one of the indicators during the evaluation, by
      surveying 240 households in three CBI and three control villages, using the World
      Bank's, Social Development Department's Social Capital Assessment Tool for data
      collection. FINDINGS: The evaluation results reveal that the social capital
      indicators like affiliation percentage; trust reciprocity; and collective action
      are better in CBI areas than their controls. CBI areas have a better access to
      public services, are more peaceful, people are more willing to help others and
      there is less segregation due to income and social status. ORIGINALITY/VALUE: The
      evaluation findings support the use of social capital indicators for
      investigating the impact and affectivity of CBI for health and development, and
      underlines the need for their consideration during implementation processes and
      further investigation.

PMID- 19862868
TI  - Treat yourself to a new set of teaching skills.

PMID- 19862867
TI  - Sexual harassment--a touchy subject for nurses.
AB  - PURPOSE: The purpose of this paper is to examine prevalence of sexual harassment
      (SH) in nursing and the environmental factors that contribute to incidents of SH.
      DESIGN/METHODOLOGY/APPROACH: A mixed-method research methodology is adopted. A
      total of 538 questionnaires are collected from nurses working in eight different
      hospitals across metropolitan and rural areas in Australia. A total of 23 in
      depth semi-structured interviews are conducted. FINDINGS: Prevalence of SH in
      nursing is high with 60 percent of female nurses and 34 percent of male nurses
      reporting a SH incident in the two-year period prior to this paper. The
      questionnaire data suggest that patients are the most likely perpetrator,
      however, the interviews name physicians as typical perpetrators. A model is
      tested via structural equation modelling and revealed that leadership behaviors,
      an unbalanced job gender ratio and no prior socialization are positively
      associated with SH. RESEARCH LIMITATIONS/IMPLICATIONS: This paper closes gaps in
      theory by introducing a new framework explaining the contextual factors that
      heighten a nurses' probability of being harassed. Some variables such as
      organizational culture and specific nursing units have not been explored and can
      be considered a limitation of the paper. PRACTICAL IMPLICATIONS: The results of
      this paper assist health professionals to adopt proactive practices for managing
      SH and plan a workforce where SH is minimized. ORIGINALITY/VALUE: This paper
      illustrates the prevalence of different types of SH and the causes for male and
      female nurses that have not been investigated previously. The results help health
      managers make informed decisions in regard to intervention strategies.

PMID- 19862869
TI  - Bacterial diversity in surgical site infections: not just aerobic cocci any more.
AB  - OBJECTIVE: To evaluate the microbial diversity in chronic surgical site
      infections (SSIs). METHOD: Bacterial populations in 23 chronic SSIs were
      identified using bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP),which
      is an universal bacterial identification method.These results were then validated
      using quantitative polymerase chain reaction (qPCR). RESULTS: bTEFAP identified
      two previously uncharacterised Bacteroidales in all of the SSIs and showed that
      it was the predominant population in the majority of these chronic wounds. Other
      bacteria identified included Corynebacterium spp., Peptoniphilus spp.,
      Staphylococcus spp., Staphylococcus aureus, Serratia marcescens, Prevotella spp.
      and Pseudomonas aeruginosa. Rarefaction analysis of the data indicated that, on
      average, six genera occurred in any given SSI, suggesting that such infections
      are multispecies. On average, over 60% of the bacteria evaluated in the SSIs were
      anaerobic bacilli. The previous literature indicates that aerobic cocci
      predominate in such wounds. CONCLUSION: This modern molecular survey indicates
      that our previous understanding of which bacteria cause SSIs may be faulty. The
      high prevalence of anaerobic bacilli and the overwhelming predominance of two
      previously uncharacterised Bacteroidales suggest that such bacteria may be a
      leading contributor to such infections. Further research on the identification
      and treatment of such bacteria are warranted.

PMID- 19862870
TI  - Malignant fungating wounds: key symptoms and psychosocial issues.
AB  - Living with a malignant wound can be an overwhelming experience for the patient
      and their family, yet the psychosocial effects are often overlooked at
      assessment. If care is to be holistic, then these issues must be addressed.

PMID- 19862871
TI  - An unusual complication of TNP.

PMID- 19862872
TI  - Principles and practices of treating facial cuts during boxing matches.

PMID- 19862873
TI  - A review of the literature on topical therapies for diabetic foot ulcers. Part 2:
      Advanced treatments.
AB  - Following part one, which presented background to diabetic foot ulcers and the
      principles thought to explain hard-to-heal wounds, part two of this series
      reviews the efficacy and cost data indicating that certain wound treatments may
      be of benefit.

PMID- 19862874
TI  - In vitro comparison of antimicrobial activity of iodine and silver dressings
      against biofilms.
AB  - OBJECTIVE: To compare the antimicrobial effectiveness of silver- and iodine
      containing wound dressings against preformed mature biofilms of pathogenic wound
      bacteria grown in vitro. METHOD: Biofilms of Pseudomonas aeruginosa and
      Staphylococcus aureus were grown within an in vitro flat bed perfusion biofilm
      model. Mature biofilms were removed and exposed to wound dressings containing
      either silver or iodine (Aquacel Ag and Iodozyme) within a static diffusion
      method, for up to 24 hours. This method was designed to reflect certain key
      features that determine antimicrobial activity within the wound. The numbers of
      viable bacteria surviving in the biofilms were determined at set time intervals
      over the test period. RESULTS: Both test dressings exerted an antimicrobial
      effect against the target species biofilms, although the iodine dressing was more
      efficacious under the experimental conditions employed. CONCLUSION: There are
      large and potentially significant differences (as measured in vitro) in the
      effectiveness of wound dressings containing broad-spectrum antimicrobial agents
      such as silver and iodine against specific types of bacterial biofilms.

PMID- 19862876
TI  - Micro data assessment of Russian drug benefit monetization.
AB  - PURPOSE: The drug benefit reform implemented in Russia in 2005 allowed benefit
      groups to choose between the fixed monetary compensation or the in-kind benefits.
      This paper seeks to study the efficiency of the in-kind drug benefit system
      before and after the reform by comparing mandated groups of monetary savings
      within each of the schemes. DESIGN/METHODOLOGY/APPROACH: Pair-wise correlation
      analysis using the Federal Social Insurance Fund benefit groups database (85
      regions in 2005-2006) and two representative consumer expenditure surveys: the
      National Assessment of Population Welfare and Participation in Social Programs:
      NOBUS (47 regions, over 40,000 households, 2003) and the Russia Longitudinal
      Monitoring Survey: RLMS (32 regions, over 4000 households, 2003). FINDINGS: The
      paper finds that giving the mandated population a choice between the two schemes
      led to an increase in demand for drugs and adverse selection within the in-kind
      drug provision system. RESEARCH LIMITATIONS/IMPLICATIONS: The Federal Social
      Insurance Fund aggregated data allow one to make post-reform estimations only for
      an average representative of a certain benefit group. Employing micro data on
      both pre- and post-reform consumer behavior would become a tool for more precise
      econometric analysis. PRACTICAL IMPLICATIONS: The results of the correlation
      analysis demonstrate an imbalance in the solidarity principle and the need for
      introducing health and drug insurance mechanisms in the Russian drug benefit
      programme. ORIGINALITY/VALUE: The paper represents an attempt to use a large
      sample statistical analysis along with the Federal Social Insurance Fund data in
      order to assess drug benefit groups of behavior in Russian regions before and
      after the drug benefit reform.

PMID- 19862875
TI  - Role of macrophages in normal wound healing: an overview.
AB  - Macrophages play an essential role during inflammation in normal wound healing.
      They promote the recruitment and proliferation of fibroblasts, and express some
      of the key growth factors that stimulate angiogenesis.

PMID- 19862877
TI  - Health care reform planners and wicked problems: Is the wickedness of the
      problems taken seriously or is it even noticed at all?
AB  - PURPOSE: The purpose of this paper is to examine the planning of the National
      Health reform especially the "guarantee for care" reform within it--from the
      perspective of the concept of wicked problems. This concept asserts that it is of
      the utmost importance to see the true level of complexity of the problems in
      order to survive them. The paper tries to the answer the question of how the
      planners of the health care reforms see the problems they are trying to solve.
      DESIGN/METHODOLOGY/APPROACH: This is an interview study. A total of 12 people who
      participated in the planning of the examined reforms at some level were
      interviewed. The interview method was a semi-structured thematic interview. The
      research analysis is theory-originated content analysis. FINDINGS: The hypothesis
      is that the planners of the examined reforms do not focus enough on the
      complexity of the problems they tried to solve. The research, however, shows that
      the wickedness of the problems was often noticed. Unfortunately it was not taken
      as seriously as it should have been. In other words, the planners mostly saw that
      the problems were very complex, but even then the solutions were only like
      solutions for tame problems or messes. ORIGINALITY/VALUE: The paradigm shift from
      Newtonian science--which sees the world as a deterministic system--to a more
      complexity-endorsing view is on its way. The world is a dynamic and open system,
      which cannot be controlled. The paper makes its own contribution, from the
      perspective of health care problems and reforms, to advance this paradigm shift.

PMID- 19862878
TI  - Risky behaviour and patient safety: a critical culturist perspective.
AB  - PURPOSE: This paper aims to utilise cultural theory of risk to provide a broad
      analytic framework for examining how risk is constructed within the dominant
      discourses around patient safety within the domain of psychiatry. It also seeks
      to examine notions of blame and to consider the possibility of the creation of a
      no-blame culture. DESIGN/METHODOLOGY/APPROACH: The empirical element of the paper
      draws on qualitative interviews with a sample of psychiatrists to explore how
      culture may give rise to different perceptions and responses in respect of "risky
      behaviour" and "safe practice". FINDINGS: The paper discusses how psychiatry may
      be differentiated from other branches of medicine and concludes that the cultural
      grouping that appears to be most apposite in respect of psychiatrists is the
      egalitarian culture. However, changes in the NHS are resulting in the imposition
      of an individualistic culture on the community of psychiatrists with the effect
      that behaviours are being adopted as measures to avoid potential blame. PRACTICAL
      IMPLICATIONS: The paper finds that if the NHS is to improve patient safety then
      it must recognise that it is not possible to create a no-blame culture and,
      therefore, it is more important to consider which type of culture will impact
      most positively on patient safety. It appears that psychiatrists are being
      compelled to adopt an individualistic culture when an egalitarian culture would
      be more advantageous for patient safety. ORIGINALITY/VALUE: In contrast with the
      methodological individualism of the current safety orthodoxy which interprets
      risk as an objective and measurable phenomenon, the paper draws on cultural
      theory of risk to develop a critical perspective on current safety policy and to
      explore how "risky" and "safe" practices are socially constructed in the context
      of psychiatry.

PMID- 19862879
TI  - Organizational consciousness.
AB  - PURPOSE: The purpose of this paper is to develop a conceptual understanding of
      organizational consciousness that expands the discussion of organizational
      analysis, and use a case study to apply it in the analysis of a merger between an
      academic health center and a regional medical center.
      DESIGN/METHODOLOGY/APPROACH: The paper draws on the experiences and insights of
      scholars who have been exploring complex organizational issues in relationship
      with consciousness. FINDINGS: Organizational consciousness is the organization's
      capacity for reflection; a centering point for the organization to "think" and
      find the degree of unity across systems; and a link to the organization's
      identity and self-referencing attributes. It operates at three stages:
      reflective, social, and collective consciousness. RESEARCH
      LIMITATIONS/IMPLICATIONS: Translating abstract concepts such as consciousness to
      an organizational model is complex and interpretive. For now, the idea of
      organizational consciousness remains mostly a theoretical concept. Empirical
      evidence is needed to support the theory. PRACTICAL IMPLICATIONS: Faced with
      complicated and compelling issues for patient care, health care organizations
      must look beyond the analysis of structure and function, and be vigilant in their
      decisions on where important issues sit on the ladder of competing priorities.
      Organizational consciousness keeps the organization's attention focused on
      purpose and unifies the collective will to succeed. ORIGINALITY/VALUE: If the
      paper can come to understand how consciousness operates in organizations, and
      learn how to apply it in organizational decisions, the pay-off could be big in
      terms of leading initiatives for change. The final goal is to use what is learned
      to improve organizational outcomes.

PMID- 19862880
TI  - Authentic leadership: a new theory for nursing or back to basics?
AB  - PURPOSE: Authentic leadership is an emerging theoretical model purported to focus
      on the root component of effective leadership. The purpose of this paper is to
      describe the relevance of authentic leadership to the advancement of nursing
      leadership practice and research and address the question of whether this is a
      new theory for leadership or an old one in new packaging.
      DESIGN/METHODOLOGY/APPROACH: The paper outlines the origins and key elements of
      the model, assesses the theoretical, conceptual and measurement issues associated
      with authentic leadership and compares it with other leadership theories
      frequently reported in the nursing literature. FINDINGS: The emerging authentic
      leadership theory holds promise for explaining the underlying processes by which
      authentic leaders and followers influence work outcomes and organizational
      performance. Construct validity of authentic leadership has preliminary
      documentation and a few studies have shown positive relationships between
      authenticity and trust. Furthermore, the clarity of the authenticity construct
      and comprehensiveness of the overall theoretical framework provide a fruitful
      base for future research examining the relationship between authentic leadership
      and the creation of healthier work environments. ORIGINALITY/VALUE: A clear focus
      on the relational aspects of leadership, the foundational moral/ethical
      component, a potential linkage of positive psychological capital to work
      engagement and the emphasis on leader and follower development in the authentic
      leadership framework are closely aligned to current and future nursing leadership
      practice and research priorities for the creation of sustainable changes in
      nursing work environments.

PMID- 19862881
TI  - Green care governance: between market, policy and intersecting social worlds.
AB  - PURPOSE: Green care--the utilisation of farms as the basis for health services-
      is seen as a promising addition to other health services, and it is seen as a
      viable diversification strategy for many farm families. However, the number of
      such services is low both in Norway and in Europe in general. The development of
      green care seems to have stagnated. This paper seeks to analyze and discuss the
      case of Norwegian green care in order to reflect on the hindrances to the further
      development of a viable green care sector. DESIGN/METHODOLOGY/APPROACH: The paper
      analyzes the green care market, green care policies and the interaction of social
      worlds that are necessary to make the green care sector function smoothly.
      FINDINGS: The conclusion is that there is a sound basis for a green care market
      and that there are sufficient political support and political engagement for the
      development of green care in Norway. The problem with the green care sector is
      the interaction between the "social worlds" involved in the sector--the
      suppliers/farmers, the users, and the (public sector) buyers. It is argued that
      the development of a green care market is hampered by the lack of an
      institutional framework and a set of market devices capable of bringing key
      actors together. RESEARCH LIMITATIONS/IMPLICATIONS: The paper presents an
      analysis of the Norwegian green care sector. It shows that there are substantial
      cross-national differences between health service systems, and therefore
      comparisons between nations are difficult. However, the principal challenges-
      diverse social groups, the lack of institutional frames, and immature markets-
      are shared. Therefore, the need for further research is evident and there are
      lessons to be learned from cross-national comparison and case studies.
      ORIGINALITY/VALUE: Within the green care research field, there have been few
      social science studies that address organisational issues and the governance of
      this new and emerging business. Theoretically oriented and analytical
      contributions on organisational aspects of green care services are therefore
      timely. This paper is such a contribution.

PMID- 19862882
TI  - Matching surgical operating capacity to demand using estimates of operating
      times.
AB  - PURPOSE: This paper sets out to investigate whether demand for gynaecological
      theatre time could be described in terms of the time required to undertake
      elective operations booked for surgery, and so help match the capacity to this.
      DESIGN/METHODOLOGY/APPROACH: A questionnaire assessed the estimates for total
      operation time for seven common operations, sent to surgeons, anaesthetists and
      nursing staff in one tertiary referral and one district general hospital (total
      49 staff; response rate 58 per cent), and estimates were obtained from theatre
      computer logs. Average timings for each operation were then applied to cases
      added from clinics to the waiting list at the district general, to yield the mean
      demand for elective surgery, and were also applied to emergencies to estimate
      emergency workload. Finally these demand estimates were compared with the theatre
      capacity available. FINDINGS: The paper found no difference between the estimates
      of the three staff groups or between these and the theatre logs (p = 0.669), nor
      did it find that estimates differed between the two centers (p = 0.628).
      Including emergencies, the mean (95 per cent confidence intervals) demand at the
      district general was 2438 (1952-2924) min/week. RESEARCH
      LIMITATIONS/IMPLICATIONS: Although the paper modelled the variation in demand
      using the relevant variation in operation times, any additional variation caused
      by differences in booking rates from clinics over time was not nodelled. The
      minimum period over which data should be collected was not established. PRACTICAL
      IMPLICATIONS: The paper finds that the existing capacity of 1680 min/week did not
      match these needs and, unless it was increased, a rise in waiting lists was
      predictable. ORIGINALITY/VALUE: The paper concludes that time estimates for
      scheduled operations can be better used to assess the need for surgical operating
      capacity than current measures of demand or capacity.

PMID- 19862883
TI  - Ultrsasound in anaesthesiology and intensive care. Preface.

PMID- 19862884
TI  - Ultrasound use in non-cardiac surgery.
AB  - Ultrasound is used in anaesthesia for diagnostic and interventional reasons. This
      article gives the anaesthesiolgoist an overview about the relevant indications
      for ultrasound in non-cardiac surgical patients. Other chapters will focus in
      more detail on different aspects of ultrasound use in non-cardiac anaesthesia.
      Echocardiography is a monitoring tool for cardiac structures and function. In the
      anaesthetized patient the transoesophageal approach is preferred due to the
      unrestricted ultrasound view to the heart. Its use for non-cardiac surgery is
      discussed. The use of transcutaneous ultrasound in anaesthesia is mainly
      interventional: The puncture rate for vascular access e.g. central venous
      catheterization is higher and the procedure can be performed safer under
      continuous sonographic guidance. Nerve blockade under direct visualisation of
      target and accompanying structures has amplified the regional anaesthetic
      methods. The major nerve blocks are described and discussed.

PMID- 19862885
TI  - Use of ultrasound in the ICU.
AB  - Echography has developed as an indispensable tool in diagnosis and subsequent
      therapy in the critically ill. Although pulmonary and abdominal ultrasounds play
      a major role in their management, this article will discuss the advantages and
      indications of echocardiography in the intensive care unit (ICU). The assessment
      of morphological abnormalities, left or right ventricular malfunction, pulmonary
      arterial hypertension and valvular dysfunctions is a routine indication of
      echocardiography. Actually, besides contractility, several preload and even
      afterload indicators can also be assessed. In short, this bedside tool rapidly
      provides insight in the haemodynamics without invasive pressure estimations.

PMID- 19862886
TI  - The impact of routine trans-oesophageal echocardiography (TOE) in cardiac
      surgery.
AB  - Trans-oesophageal echocardiography (TOE) has profoundly changed cardiac surgery
      and the role of the cardiac anaesthesiologist. It has been the driving force for
      a real-time diagnostic and decision-making partnership between cardiac
      anaesthesiologists and cardiac surgeons that has significantly advanced the
      safety and effectiveness of modern cardiac surgery. With the information provided
      by TOE, anaesthesiologists and surgeons may redirect the care of cardiac surgical
      patients to decrease morbidity and mortality. As a result, routine intra
      operative TOE is an expectation in many cardiac surgical practices. While some
      colleagues continue to question whether TOE should be used routinely in all
      cardiac surgical patients, we believe that it is impossible to predict in which
      cardiac patients TOE will discover vitally important new information. Therefore,
      we recommend that in the absence of contraindication to oesophageal
      instrumentation with the probe, TOE should be performed in all cardiac surgical
      patients. With routine TOE use, TOE will have its greatest benefit.

PMID- 19862887
TI  - Ultrasound-guided haemodynamic state assessment.
AB  - The haemodynamic state refers to the integration of myocardial and vascular
      systems, and involves both left and right hearts, and systolic and diastolic
      phases. The assessment of the haemodynamic state can be performed with
      echocardiography, and provides a higher level of diagnosis than conventional
      pressure- and flow-based monitoring. Whilst hypotension alerts the practitioner
      about the existence of haemodynamic abnormality, it does not provide sufficient
      information to identify the cause or the underlying haemodynamic state. The
      premise of haemodynamic state monitoring is that better diagnosis will lead to
      more rational therapy, which in turn may improve the outcome. The haemodynamic
      state can be classified into seven broad categories: normal, empty, vasodilation,
      systolic failure, primary diastolic failure, systolic and diastolic failure and
      right ventricular failure. These are identified as patterns based upon
      ventricular size, ventricular function and left atrial (LA) filling pressure.
      Patients may have an abnormal haemodynamic state (such a systolic failure), but
      may not need active treatment if they are haemodynamically stable. However, if
      treatment is required, it can be directed according to the underlying
      haemodynamic state. For example, a patient with systolic failure may benefit from
      inotrope support, whereas an empty state acquires volume infusion and
      vasodilation requires vasopressor support.

PMID- 19862888
TI  - Limited transthoracic echocardiography assessment in anaesthesia and critical
      care.
AB  - The use of echocardiography in anaesthesia and critical care started with
      transoesophageal echocardiography, whereas transthoracic echocardiography was
      largely the domain of the cardiologist. In recent times, there has been a change
      in focus towards transthoracic echocardiography owing to the development of small
      and portable, yet high-fidelity, echocardiography machines. The cost has reduced,
      thereby increasing the availability of equipment. A parallel development has been
      the concept of limited transthoracic echocardiography that can be performed by
      practitioners with limited experience. The basis of these examinations is to
      provide the practising clinician with immediate information to help guide
      management with a focus on haemodynamic evaluation, and limited structural
      (valve) assessment to categorise whether there is a valve disorder that may or
      may not cause haemodynamic instability. The limited examination is therefore goal
      directed. A number of named examinations exist which differ in their scope and
      views. All of these require a limited knowledge base, and are designed for the
      clinician to recognise patterns consistent with haemodynamic or anatomical
      abnormalities. They range from very limited two-dimensional assessments of
      ventricular function to more complex (yet presently limited) studies such as
      HEART (haemodynamic echocardiography assessment in real time) scan, which is
      designed to provide haemodynamic state, as well as basic valvular and pericardial
      assessment. It is suitable for goal-directed examination in the operating
      theatre, emergency department or intensive care unit (ICU) and for preoperative
      screening.

PMID- 19862889
TI  - Ultrasound guided vascular access: efficacy and safety.
AB  - Central venous catheterisation and arterial catheterisation are common procedures
      performed by anaesthetists. Traditionally, the technique of locating surface
      landmarks and palpation was used to assist in vascular access. The introduction
      of perioperative ultrasonography in the past decade has dramatically changed this
      procedure. In the United States and United Kingdom, guidelines have recommended
      the use of ultrasound guidance to reduce complications and improve success in
      central venous catheterisation. This article summarises the literature on
      complication rates, efficacy and safety of ultrasound-guided vascular access
      procedures and describes a practical method of ultrasound-guided central venous
      access and arterial catheterisation.

PMID- 19862890
TI  - Ultrasound-guided nerve blocks: efficacy and safety.
AB  - The introduction of affordable, portable and high-resolution ultrasound machines
      has rejuvenated interest in regional anaesthesia. The inherent benefits of direct
      visualisation of nerves and surrounding anatomy, continual observation of the
      needle tip and spread of local anaesthetic make ultrasound-guided regional
      anaesthesia highly appealing. However, in the cost-conscious health-care setting
      and to convince sceptics, there also needs to be evidence of increased benefits
      and reduced complications. Ultrasound is a rapidly developing area of technology
      and some of the newer modalities are discussed. This article focusses on the
      recent growing evidence to support the benefits of its use in nerve and plexus
      blocks. Common complications of nerve blocks can be avoided with ultrasound but
      have still been reported. Anatomical variants have been demonstrated by
      ultrasound and it has proved to be useful in performing regional anaesthesia in
      difficult situations or where peripheral nerve stimulation is unsuccessful or
      inappropriate.

PMID- 19862891
TI  - Goal-directed fluid management with trans-oesophageal Doppler.
AB  - Major surgery is associated with significant trauma and is a potential cause of
      multiple system organ failure and death. Measurement of cardiac output using a
      variety of techniques during the perioperative period has enabled practitioners
      to proactively optimise stroke volume and cardiac output in an attempt to reduce
      postoperative complications. Although pulmonary artery catheter has been widely
      used and considered as the gold standard for measuring cardiac output, recent
      advancement of technology has seen the development of a number of less-invasive
      haemodynamic monitors. Oesophageal Doppler ultrasonography is a minimally
      invasive method for measuring stroke volume and cardiac output. It is user
      friendly and is one of the few low-invasive technologies to date, which has been
      used successfully to guide intra-operative fluid administration, resulting in
      improvement in outcome and significant reduction in duration of hospital stay.

PMID- 19862892
TI  - Epiaortic ultrasound assessment of the aorta in cardiac surgery.
AB  - The dislodgement of atheroma from the ascending aorta and proximal arch is a
      major cause of stroke and neurological injury following cardiac surgery. The
      accurate detection of atheroma prior to aortic manipulation is necessary to
      facilitate surgical strategies to reduce the risk of embolisation. The
      traditional method for atheroma detection is manual palpation by the surgeon.
      This technique misses about half the number of the atheroma lesions, as the soft
      (non-calcified) lesions offer little resistance to the surgeon's fingers. Trans
      oesophageal echocardiography (TOE) is commonly used in cardiac surgery, but the
      interposition of the bronchus between the aorta and the oesophagus causes an
      ultrasound 'blind spot' in the ascending aorta and proximal arch, such that it
      does not offer improved detection compared to manual palpation. Accurate
      detection of atheroma requires direct ultrasound assessment using epiaortic
      scanning, with a high-frequency, linear-array probe. This allows the surgeon to
      correctly assess and localise any atheroma. In this article, a suggested
      epiaortic examination sequence is described and strategies for surgeons to avoid
      atheroma are discussed.

PMID- 19862893
TI  - Ultrasound in trauma.
AB  - Point-of-care ultrasound is well suited for use in the emergency setting for
      assessment of the trauma patient. Currently, portable ultrasound machines with
      high-resolution imaging capability allow trauma patients to be imaged in the pre
      hospital setting, emergency departments and operating theatres. In major trauma,
      ultrasound is used to diagnose life-threatening conditions and to prioritise and
      guide appropriate interventions. Assessment of the basic haemodynamic state is a
      very important part of ultrasound use in trauma, but is discussed in more detail
      elsewhere. Focussed assessment with sonography for Trauma (FAST) rapidly assesses
      for haemoperitoneum and haemopericardium, and the Extended FAST examination
      (EFAST) explores for haemothorax, pneumothorax and intravascular filling status.
      In regional trauma, ultrasound can be used to detect fractures, many vascular
      injuries, musculoskeletal injuries, testicular injuries and can assess foetal
      viability in pregnant trauma patients. Ultrasound can also be used at the bedside
      to guide procedures in trauma, including nerve blocks and vascular access.
      Importantly, these examinations are being performed by the treating physician in
      real time, allowing for immediate changes to management of the patient.
      Controversy remains in determining the best training to ensure competence in this
      user-dependent imaging modality.

PMID- 19862894
TI  - Training guidelines for ultrasound: worldwide trends.
AB  - Sound travels through objects that block light. Only very recently has technology
      advanced enough to decipher ultrasound for medical use. Machines have become
      smaller, cheaper, more versatile and more advanced than ever before. The medical
      use of ultrasound spreads across many fields so that traditional areas no longer
      have a monopoly. With this comes the question of training doctors. This has been
      done by various colleges and societies worldwide. Some have been quicker to act
      than others. There also needs to be an understanding of when broad experience and
      advanced technical skills are required or when limited skills will do. In
      addition, some procedures can be performed more safely with ultrasound where the
      knowledge of ultrasound is not paramount. This article covers current provision
      of training in echocardiography and ultrasound in areas relevant to anaesthetists
      who are working in critical care (including accident and emergency) and complex
      surgery (mainly cardiac).

PMID- 19862895
TI  - A concurrent validity study between the Hypnotic Induction Profile (HIP) and the
      Stanford Hypnotic Clinical Scale for Adults (SHCS:A) in an inpatient sample: a
      brief report.
AB  - The Hypnotic Induction Profile (HIP) is a brief, standardized assessment of
      hypnotizability which takes 5-10 minutes to administer. The Stanford Hypnotic
      Clinical Scale for Adults (SHCS:A) is a different clinical measure of
      hypnotizability that takes about 20-25 minutes to administer. Although both
      scales purport to measure the same thing, they were based on different theories
      of hypnosis and constructed using different psychometric techniques. The present
      investigation is a concurrent validation study comparing scores on the two
      instruments in a sample of 24 inpatients. The correlation between the SHCS:A and
      HIP Induction score was 0.41 (p < .01). However, the Eye Roll Sign (ERS) did not
      correlate significantly with either the SHCS:A (.04, ns) or the HIP-IND score (
      .05, ns). These results indicate that while scores on the HIP and SHCS:A are
      significantly correlated the inter-correlations are not high enough to consider
      them as interchangeable measures. Implications of these findings for future
      research are discussed.

PMID- 19862896
TI  - ECEM (Eye Closure, Eye Movements): application to depersonalization disorder.
AB  - Eye Closure, Eye Movements (ECEM) is a hypnotically-based approach to treatment
      that incorporates eye movements adapted from the Eye Movement Desensitization and
      Reprocessing (EMDR) protocol in conjunction with hypnosis for the treatment of
      depersonalization disorder. Depersonalization Disorder has been differentiated
      from post-traumatic stress disorders and has recently been conceptualized as a
      subtype of panic disorder (Baker et al., 2003; David, Phillips, Medford, &
      Sierra, 2004; Segui et. al., 2000). During ECEM, while remaining in a hypnotic
      state, clients self-generated six to seven trials of eye movements to reduce
      anticipatory anxiety associated with depersonalization disorder. Eye movements
      were also used to process triggers that elicited breath holding, often followed
      by episodes of depersonalization. Hypnotic suggestions were used to reverse core
      symptoms of depersonalization, subjectively described as "feeling unreal" (Simeon
      et al., 1997).

PMID- 19862898
TI  - Diagnosis and hypnotic treatment of an unusual case of hysterical amnesia.
AB  - This article reports on the use of hypnosis to facilitate the diagnostic process
      and the treatment of an unusual case of adult psychogenic amnesia. An Iraqi
      citizen living in the U.S. developed an atypical case of Dissociative Amnesia,
      Systematized type, post-automotive collision. The amnesia presented with features
      encompassing complete loss of the patient's native language. Dissociation theory
      as a conceptualization of hysterical reactions was employed as the basis in the
      formulation of this case. The differential diagnosis was facilitated by the
      Hypnotic Diagnostic Interview for Hysterical Disorders (HDIHD) Adult Form, an
      interview tool specifically designed for cases such as this. Treatment consisted
      exclusively of ego strengthening and time projection approaches in hypnosis. It
      was hypothesized that, as the coping capacities became more viable, the
      dissociative symptoms would remiss. After 6 weekly visits the patient regained
      complete command of his native language. Follow-up at 6 months indicated that the
      patient remained devoid of symptoms.

PMID- 19862897
TI  - Ambroise August Liebeault and psychic phenomena.
AB  - Some nineteenth-century hypnosis researchers did not limit their interest to the
      study of the conventional psychological and behavioral aspects of hypnosis, but
      also studied and wrote about psychic phenomena such as mental suggestion and
      clairvoyance. One example, and the topic of this paper, was French physician
      Ambroise August Liebeault (1823-1904), who influenced the Nancy school of
      hypnosis. Liebeault wrote about mental suggestion, clairvoyance, mediumship, and
      even so-called poltergeists. Some of his writings provide conventional
      explanations of the phenomena. Still of interest today, Liebeault's writings
      about psychic phenomena illustrate the overlap that existed during the nineteenth
      century between hypnosis and psychic phenomena--an overlap related to the
      potentials of the mind and its subconscious activity.

PMID- 19862899
TI  - Hypnosis: seventy years of amazement, and still don't know what it is!
AB  - This paper has reviewed the author's experience with hypnosis and related
      therapies from 1934 through World War II, psychological warfare, multiple
      personality, the origins and feuding of hypnosis societies, the development of
      hypnotic ego state therapy and the unique contributions of his colleague and
      wife, Helen Watkins.

PMID- 19862900
TI  - Lasting beauty. Furnishings stand up to harsh environment.

PMID- 19862901
TI  - In sickness & health. Consumer-influenced design reaches out to community.

PMID- 19862902
TI  - Shock resistant. Preventing arc-flash hazards in the hospital setting.

PMID- 19862903
TI  - Picture perfect. Installing an integrated operating room.

PMID- 19862904
TI  - What's new? Joint Commission issues midyear changes.

PMID- 19862905
TI  - Keep 'em moving. Nine ES strategies to help improve patient flow.

PMID- 19862906
TI  - A perfect match. Nurses take on genetics, genomics--and make a difference.

PMID- 19862907
TI  - Genetics and genomics to general nursing practice: an exemplar.

PMID- 19862908
TI  - Health care reform gets personal.

PMID- 19862909
TI  - Experiencing violence in EDS.

PMID- 19862910
TI  - Introducing the Pathway to Excellence program.

PMID- 19862911
TI  - Today's assignment: find more nurse educators.

PMID- 19862912
TI  - Health care workers: roll up your sleeve. Campaigns take aim at seasonal
      influenza, H1N1.

PMID- 19862913
TI  - Integrated assessment of river health based on water quality, aquatic life and
      physical habitat.
AB  - The health conditions of Liao River were assessed using 25 sampling sites in
      April 2005, with water quality index, biotic index and physical habitat quality
      index. Based on the method of cluster analysis (CA) for water quality indices, it
      revealed that heavily polluted sites of Liao River are located at estuary and
      mainstream. The aquatic species surveyed were attached algae and benthic
      invertebrates. The result showed that the diversity and biomass of attached algae
      and benthic index of biotic integrity (B-IBI) were degrading as the chemical and
      physical quality of water bodies deteriorating. Physiochemical parameters, BOD5,
      COD(Cr), TN, TP, NH3-N, DO, petroleum hydrocarbon and conductivity, were
      statistically analyzed with principal component analysis and correlation
      analysis. The statistical results were incorporated into the integrated assessing
      water quality index, combining fecal coliform count, attached algae diversity, B
      IBI and physical habitat quality score. A comprehensive integrated assessing
      system of river ecological health was established. Based on the systimetic
      assessment, the assessed sites are categorized into 9 "healthy" and "sub-healthy"
      sites and 8 "sub-sick" and "sick" sites.

PMID- 19862914
TI  - Kinetics and corrosion products of aqueous nitrate reduction by iron powder
      without reaction conditions control.
AB  - Although considerable research has been conducted on nitrate reduction by zero
      valent iron powder (Fe0), these studies were mostly operated under anaerobic
      conditions with invariable pH that was unsuitable for practical application.
      Without reaction conditions (dissolved oxygen or reaction pH) control, this work
      aimed at subjecting the kinetics of denitrification by microscale Fe0 (160-200
      mesh) to analysis the factors affecting the denitrification of nitrate and the
      composition of iron reductive products coating upon the iron surface. Results of
      the kinetics study have indicated that a higher initial concentration of nitrate
      would yield a greater reaction rate constant. The reduction rate of nitrate
      increased with increasing Fe0 dosage. The reaction can be described as a pseudo
      first order reaction with respect to nitrate concentration or Fe0 dosage.
      Experimental results also suggested that nitrate reduction by microscale Fe0
      without reaction condition control primarily was an acid-driven surface-mediated
      process, and the reaction order was 0.65 with respect to hydrogen ion
      concentration. The analyses of X-ray diffractometry and X-ray photoelectron
      spectroscopy indicated that a black coating, consisted of Fe2O3, Fe3O4 and
      FeO(OH), was formed on the surface of iron grains as an iron corrosion product
      when the system initial pH was lower than 5. The proportion of FeO(OH) increased
      as reaction time went on, whereas the proportion of Fe3O4 decreased.

PMID- 19862915
TI  - Effect of carbon source on the denitrification in constructed wetlands.
AB  - The ability of constructed wetlands with different plants in nitrate removal were
      investigated. The factors promoting the rates of denitrification including
      organic carbon, nitrate load, plants in wetlands, pH and water temperature in
      field were systematically investigated. The results showed that the additional
      carbon source (glucose) can remarkably improve the nitrate removal ability of the
      constructed wetland. It demonstrated that the nitrate removal rate can increase
      from 20% to more than 50% in summer and from 10% to 30% in winter, when the
      nitrate concentration was 30-40 mg/L, the retention time was 24 h and 25 mg/L
      dissolved organic carbon (DOC) was ploughed into the constructed wetland.
      However, the nitrite in the constructed wetland accumulated a little with the
      supply of the additional carbon source in summer and winter, and it increased
      from 0.15 to 2 mg/L in the effluent. It was also found that the abilities of
      plant in adjusting pH and temperature can result in an increase of
      denitrification in wetlands. The seasonal change may also impact the
      denitrification.

PMID- 19862916
TI  - Effect of background electrolytes on the adsorption of nitroaromatic compounds
      onto bentonite.
AB  - To further elucidate interaction of nitroaromatic compounds with mineral surface,
      the sorption of m-dinitrobenzene (m-DNB) and nitrobenzene to original bentonite
      in aqueous solution containing different electrolytes (i.e., KCl, NH4Cl, CaCl2
      and Tetramethylammonium bromide (TMAB)) was studied. The sorption of m-DNB was
      greatly enhanced with the presence of KCl and NH4Cl, while little influence was
      observed with CaCl2 and TMAB, following the order of KC1 > NH4Cl >> TMAB, CaCl2,
      or DI water. For nitrobenzene, sorption enhancement only occurred at high
      nitrobenzene concentrations in the presence of KCl, and the solute equilibrium
      concentration at inflexion point was lowered with increasing KCl concentration.
      These sorption enhancements were significantly promoted with the increase of
      electrolyte concentration. The salting-out effect is insufficient to account for
      the sorption enhancement by original bentonite with increasing KCl or NH4Cl
      concentration. X-ray diffraction patterns of bentonite suspensions indicated that
      the sorption enhancement of m-DNB was attributed to the intercalation of K+ or
      NH4+ into bentonite interlayer and then dehydration with m-DNB to form inner
      sphere complexes, which caused previously expanded bentonite interlayers to
      collapse in aqueous suspension, thus further enhanced the interaction of phenyl
      with siloxane surface. In comparison, the sorption enhancement of NB is
      attributed to the formation of outer-sphere complexes with K+ at high solute
      loadings (> 200-400 mg/kg). The sorption of m-DNB to initially modified TMA(+)
      bentonite and K(+)-bentonite was almost the same as respective sorption to
      original bentonite in solution containing TMA+ and K+.

PMID- 19862917
TI  - Potential toxic risk of heavy metals from sediment of the Pearl River in South
      China.
AB  - Based on the monitoring of five heavy metal elements in the surface sediments of
      the Pearl River in South China, potential toxicity of the heavy metals was
      assessed using consensus-based sediment quality guidelines (SQGs) method and geo
      accumulation (I(geo)) index method. The monitoring results showed the heavy metal
      concentrations were significantly and positively correlated with each other,
      demonstrating a common trend in variation of concentration in the surface
      sediments. The assessment using the consensus-based SQGs method showed the
      potential toxicity of Cu was the highest, and Cd was the lowest. The evaluation
      based on mean probable effect concentration (PEC) quotient showed the region was
      seriously polluted with high toxicity heavy metals. Correlation analysis revealed
      a significant and positive correlation between the mean PEC quotient and the
      average of I(geo) with a correlation coefficient of 0.926 (n = 23, P < 0.01). In
      conclusion, the consensus-based SQGs and mean PEC quotient are applicable to
      assess potential toxicity risks of heavy metals in freshwater sediments in the
      Pearl River.

PMID- 19862918
TI  - Impact of dynamic distribution of floc particles on flocculation effect.
AB  - Polyaluminum chloride (PAC) was used as coagulant and suspended particles in
      kaolin water. Online instruments including turbidimeter and particle counter were
      used to monitor the flocculation process. An evaluation model for demonstrating
      the impact on the flocculation effect was established based on the multiple
      linear regression analysis method. The parameter of the index weight of channels
      quantitatively described how the variation of floc particle population in
      different size ranges cause the decrement of turbidity. The study showed that the
      floc particles in different size ranges contributed differently to the decrease
      of turbidity and that the index weight of channel could excellently indicate the
      impact degree of floc particles dynamic distribution on flocculation effect.
      Therefore, the parameter may significantly benefit the development of coagulation
      and sedimentation techniques as well as the optimal coagulant selection.

PMID- 19862919
TI  - Mechanism of calcium mitigating membrane fouling in submerged membrane
      bioreactors.
AB  - Two parallel membrane bioreactors (MBRs) were operated under different calcium
      dosages (168.5, 27 mg/L) to gain a better understanding of the mechanism of
      retarding membrane fouling by adding calcium. The results showed that the
      particle size of sludge flocs increased and the particle size distribution tended
      to be narrow at the optimum dosage (168.5 mg/L). Calcium was effective in
      decreasing loosely bound extracellular polymeric substances (LB-EPS) in microbial
      flocs and soluble microbial products (SMP) in the supernatant at the dosage of
      168.5 mg/L by strengthening the neutralization and bridging of EPS with flocs.
      Furthermore, the amount of CODs and CODc decreased in both the mixed liquor and
      the fouling cake layer on the membrane surface. In order to compare the
      filtration characteristics of cake layers from the MBRs with the two calcium
      dosages, the specific cake resistance and the compressibility coefficient were
      measured. The specific cake resistance from the MBR with optimum dosage (168.5
      mg/L) was distinctly lower than that with low dosage (27 mg/L). The
      compressibility coefficient of the cake layers under two dosages were
      respectively attained as 0.65, 0.91. Scanning electron microscopy (SEM) and three
      dimensional confocal scanning laser microscope analysis (CLSM) images were
      utilized to observe the gel layer directly.

PMID- 19862920
TI  - Influence of the wastewater composition on denitrification and biological P
      removal in the S-DN-P process: (c) dissolved and undissolved substrates.
AB  - The denitrification and P-removal in the sorption-denitrification-P-removal (S-DN
      P) process were carried out under various wastewater compositions. It is noted
      that P-removal largely depends on the wastewater composition as well to the
      quantity of the substrates present in wastewater fraction. Three different
      wastewater fractions are obtained as: raw wastewater, dissolved wastewater
      (obtained with filtration using 0.45 microm filter), and undissolved wastewater
      (i.e., infiltrate obtained by above filtration). The ratio of P
      release/COD(tolal)-consumption clearly inferred that undissolved wastewater
      possess very low value i.e., 0.0008 followed by raw wastewater 0.008 and
      dissolved wastewater 0.03. When this ratio was nearby 0.01, enhanced P-removal
      was observed. Moreover, the ratio of P-uptake to NO3(-)-N decomposition for raw
      wastewater was two times for dissolved wastewater. Interestingly, it was observed
      that the P-removal and denitrification depend not only on the dissolved
      substrates but also the undissolved substrates present in the wastewater. The
      result of the P-removal obtained with this S-DN-P process did not show a big
      difference of 36%, 34% and 30%, respectively, for raw, dissolved and undissolved
      wastewater.

PMID- 19862921
TI  - One century record of contamination by polycyclic aromatic hydrocarbons and
      polychlorinated biphenyls in core sediments from the southern Yellow Sea.
AB  - Sixteen polycyclic aromatic hydrocarbons (PAHs) and 28 polychlorinated biphenyls
      (PCBs) were measured at a 2-cm interval in a core sample from the middle of the
      southern Yellow Sea for elucidating their historical variations in inflow and
      sources. The chronology was obtained using the 210pb method. PAHs concentrations
      decreased generally with depth and two climax values occurred in 14-16 cm and 20
      22 cm layers, demonstrating that the production and usage of PAHs might reach
      peaks in the periods of 1956-1962 and 1938-1944. The booming economy and the navy
      battles of the Second World War might explain why the higher levels were detected
      in the two layers. The result of principal component analysis (PCA) revealed that
      PAHs were primarily owing to the combustion product. Down-cored variation of PCB
      concentrations was complex. Higher concentrations besides the two peaks being the
      same as PAHs were detected from 4 to 8 cm, depositing from 1980 to 1992, which
      probably resulted from the disposal of the out-dated PCB-containing equipment.
      The average Cl percentage of PCBs detected was similar to that of the mixture of
      Aroclor 1254 and 1242, suggesting they might origin from the dielectrical and
      heat-transfer fluid. The total organic carbon (TOC) content played a prevalent
      role in the adsorption of high molecular weight PAHs (> or = 4-ring), while no
      obvious relationship among total PCBs, the concentration of congeners, and TOC
      was found.

PMID- 19862922
TI  - A novel aminated polymeric adsorbent for removing refractory dissolved organic
      matter from landfill leachate treatment plant.
AB  - Refractory dissolved organic matter (DOM) from landfill leachate treatment plant
      was with high dissolved organic carbon (DOC) content. An aminated polymeric
      adsorbent NDA-8 with tertiary amino groups and sufficient mesopore was
      synthesized, which exhibited high adsorption capacity to the DOM (raw water after
      coagulation). Resin NDA-8 performed better in the uptake of the DOM than resin
      DAX-8 and A100. Electrostatic attraction was considered as the decisive
      interaction between the adsorbent and adsorbate. Special attention was paid to
      the correlation between porous structure and adsorption capacity. The mesopore of
      NDA-8 played a crucial role during uptake of the DOM. In general, resin in
      chloride form performed a higher removal rate of DOC. According to the column
      adsorption test, total adsorption capacity of NDA-8 was calculated to 52.28 mg
      DOC/mL wet resin. 0.2 mol/L sodium hydroxide solution could regenerate the
      adsorbent efficiently.

PMID- 19862923
TI  - Reduction of VOC emissions by a membrane-based gas absorption process.
AB  - A membrane-based gas absorption (MGA) process was evaluated for the removal of
      volatile organic compounds (VOCs) based on C6H6/N2 mixture. The absorption of
      C6H6 from a C6H6/N2 mixture was investigated using a hydrophobic polypropylene
      hollow fiber membrane contactor and the aqueous solution of N-formyl morpholine
      (NFM) as absorbent. The effects of various factors on the overall mass transfer
      coefficient was investigated. The experimental results showed that the removal
      efficiency of C6H6 could reach 99.5% in present studied system. A mathematical
      model based on resistance-in-series concept was presented to predict the value of
      overall mass transfer coefficient. The average error between the predicted and
      experimental values is 7.9%. In addition, conventional packed columns for VOCs
      removal was also evaluated for comparison.

PMID- 19862924
TI  - Laboratory simulation of SO2 heterogeneous reactions on hematite surface under
      different SO2 concentrations.
AB  - The variations of sulfate formation and optical coefficients during SO2
      heterogeneous reactions on hematite surface under different SO2 concentrations
      were examined using in situ diffuse reflectance infrared Fourier transform
      spectroscopy (DRIFTS) and ion chromatograph (IC). Laboratory experiments revealed
      that within ambient SO2 of 0.51-18.6 ppmv, sulfate product, producing velocity,
      absorption and backward scattering coefficients showed an increasing trend with
      SO2 concentration. Under given SO2 concentration, the velocity of sulfate
      producing performed an evolution of initial increasing, midterm decreasing and
      final stabilizing. The reactive uptake and Brunauer-Emmett-Teller (BET) uptake
      coefficients of heterogeneous reactions rose with SO2 and exhibited high
      reactivities. Considering global warming, this result is important for the
      knowledge of heterogeneous reactions of SO2 on mineral particle surface in the
      atmosphere and the assessment of their impacts on radiative forcing.

PMID- 19862925
TI  - Acid deposition critical loads modeling for the simulation of sulfur exceedance
      and reduction in Guangdong, China.
AB  - The current acid deposition critical loads in Guangdong, China were calculated
      using the PROFILE model with a 3 km x 3 km resolution. Calculations were carried
      out for critical loads of potential acidity, actual acidity, sulfur and nitrogen,
      with values in extents of 0-3.5, 0-14.0, 0-26.0 and 0-3.5 kmol/(hm2 x year),
      respectively. These values were comparable to previously reported results and
      reflected the influences of vegetation and soil characteristics on the soil acid
      buffering capacity. Simulations of SO2 emission and sulfur deposition in this
      study showed that sulfur deposition core areas mirrored SO2 emission centers. The
      prediction of sulfur deposition after 20% and 40% reduction of SO2 emission
      suggested that the reduction of area sources contributed greatly to the decrease
      of sulfur deposition. Thus, abatement of area source emissions could be the
      primary way to mitigate sulfur deposition in Guangdong to meet both the
      provincial and national regulations of air pollution control.

PMID- 19862926
TI  - Atmospheric lead pollution in fine particulate matter in Shanghai, China.
AB  - The Pb-monitoring program was extended for 6 years from 2002 to 2007 at 17
      representative urban sites (6 traffic, 5 industrial, and 6 residential sites),
      and 3 suburban sites to assess the lead pollution in fine particulate matter
      (PM2.5) after phasing out leaded gasoline in Shanghai. Compared with Pb levels
      reported in other places, the Pb pollution in Shanghai is still serious after
      phasing out leaded gasoline, which remains at high concentration range (213-176
      ng/m3) in PM2.5 in winter. Significant spatial variation of Pb concentrations and
      strong seasonal variation of higher Pb concentration in winter than that in
      summer were detected. The size distribution of Pb in particulate matter has a
      unimodal mode that peaks at approximately 0.154-1.59 microm particle diameter,
      indicating that Pb is mainly concentrated in fine fraction. Lead in the fine
      fraction is enriched by a factor of 10(3)-10(4) relative to Pb abundance in
      crust. Eight categories of Pb pollution sources were identified in the PM2.5 in
      the winter of 2007 in Shanghai. The important emission sources among them are
      vehicle exhaust derived from combustion of unleaded gasoline, metallurgic
      industry emission, and coal combustion emission.

PMID- 19862928
TI  - Adsorption characteristic of bensulfuron-methyl at variable added Pb2+
      concentrations on paddy soils.
AB  - The combined pollution of heavy metal Pb2+ and bensulfuron-methyl (BSM),
      originating from chemical herbicides, in agro-ecological environments has become
      commonplace in southern China. The adsorption of BSM on three paddy soils in the
      presence of Pb2+ was examined using high-performance liquid chromatograph (HPLC).
      Results indicated that adsorption of BSM could accurately be described by a
      Freundlich isotherm equation with correlation constant (R) > 0.98, irrespective
      of the presence of spiked Pb2+. Of the various factors influencing BSM sorption,
      soil pH appeared to be the most influential. The constant K(f) of Freundlich
      isotherm equation tended to increase with increasing Pb2+ concentration in soil
      which indicated that the spiked of Pb2+ in paddy soils would promote the sorption
      of BSM. deltaG(theta) of BSM in three paddy soils was less than 40 kJ/mol in all
      treatments, indicating the adsorption of BSM is mainly physical in nature. The
      elution of soil dissolved organic matter (DOM) enhanced the adsorption of BSM in
      paddy soils. The mechanisms involved in the promotion effects of the spiked Pb2+
      on BSM adsorption might be the modified surface characteristics of paddy soil
      solids due to the soil acidification and the increase of soil organic matter
      concentration because of DOM binding.

PMID- 19862927
TI  - Cadmium uptake and speciation changes in the rhizosphere of cadmium accumulator
      and non-accumulator oilseed rape varieties.
AB  - Characteristics of cadmium (Cd) uptake kinetics and distribution of Cd speciation
      in the rhizosphere for Cd accumulator and non-accumulator oilseed rape varieties
      were investigated under nutrient solution and rhizobox soil culture conditions.
      The results showed that the maximal influx (V(max)) for Cd2+ and Km were
      significantly different for the two oilseed rape varieties. The value of V(max)
      for Cd accumulator oilseed rape Zhucang Huazi was two-fold greater than that for
      oilseed rape Chuan you II-93. The exchangeable Cd concentration in the
      rhizosphere was significantly lower than in non-rhizospheric soils supplemented
      with CdSO4 for both the varieties. Carbonate-bound Cd in the rhizosphere of Cd
      accumulator oilseed rape was significantly higher than that in the rhizosphere of
      non-accumulator oilseed rape and non-rhizospheric soil. Cd accumulator oilseed
      rape had a higher Cd2+ affinity and more ability to uptake insoluble Cd in the
      soil than the non-accumulator oilseed rape.

PMID- 19862929
TI  - Enhanced adaptability of Sesbania rostrata to Pb/Zn tailings via stem nodulation.
AB  - Sesbania rostrata is wellknown for its stem nodulation, but the roles of stem
      nodulation in root nodulation and adaptation of S. rostrata to Pb/Zn-enriched
      tailings environment has been poorly understood. We investigated the effects of
      inoculating (with stem nodule treatment) and non-inoculating (without stem nodule
      treatment) Azorhizobium caulinodans on the growth, root nodulation, and N
      fixation of S. rostrata grown on three different types of soil substrata: Pb/Zn
      tailings, garden soil amended tailings, and garden soil. The results showed that
      plant height, stem basal diameter, biomass, chlorophyll content, nitrogen content
      and N-accumulation per plant were 2.3%-4.9%, 2.2%-7.7%, 27.8%-72.2%, 17.1%-23.5%,
      12.3%-34.2%, and 43.1%-131.2%, respectively, higher in treatments with stem
      nodule than those without stem nodule for the same soil substrate. With respect
      to soil substrata, all measurements had consistently higher values in tailings
      than in amended tailings and garden soil, indicating that the poorer the soil
      condition, the greater the contribution of stem nodule. In contrast, the number
      and fresh weight of root nodules on plants without stem nodule were 6.9-11.6
      times and 5.8-29.0 times higher than those with stem nodule, respectively,
      especially with respect to the plants grew on Pb/Zn tailings. In general, stem
      nodulation favored plant growth and nitrogen fixation of S. rostrata, but
      suppressed root nodulation. With the ability of stem and root nodulation, S.
      rostrata can be used as a pioneer plant species for remediation of Pb/Zn
      tailings.

PMID- 19862930
TI  - Response of soil catalase activity to chromium contamination.
AB  - The impact of chromium(III) and (VI) forms on soil catalase activity was
      presented. The Orthic Podzol, Haplic Phaeozem and Mollic Gleysol from different
      depths were used in the experiment. The soil samples were amended with solution
      of Cr(III) using CrCl3, and with Cr(VI) using K2Cr2O7 in the concentration range
      from 0 to 20 mg/kg, whereas the samples without the addition of chromium served
      as control. Catalase activity was assayed by one of the commonly used
      spectrophotometric methods. As it was demonstrated in the experiment, both
      Cr(III) and Cr(VI) have an ability to reduce soil catalase activity. A chromium
      dosage of 20 mg/kg caused the inhibition of catalase activity and the
      corresponding contamination levels ranged from 75% to 92% for Cr(III) and 68% to
      76% for Cr(VI), with relation to the control. Catalase activity reached maximum
      in the soil material from surface layers (0-25 cm), typically characterized by
      the highest content of organic matter creating favorable conditions for
      microorganisms.

PMID- 19862931
TI  - Comprehensive characterization of indoor airborne bacterial profile.
AB  - This is the first detailed characterization of the airborne bacterial profiles in
      indoor environments. Two restaurants were selected for this study. Fifteen genera
      of bacteria were isolated from each restaurant and identified by three different
      bacterial identification systems including MIDI, Biolog and Riboprinter. The
      dominant bacteria of both restaurants were Gram-positive bacteria in which
      Micrococcus and Bacillus species were the most abundant. Most bacteria identified
      were representative species of skin and respiratory tract of human, and soil.
      Although the bacterial levels in these two restaurants were below the limit of
      the Hong Kong Indoor Air Quality Objective (HKIAQO) Level 1 standard (i.e., < 500
      cfu/m3), the majority of these bacteria were opportunistic pathogens. These
      results suggested that the identity of airborne bacteria should also be included
      in the IAQ to ensure there is a safety guideline for the public.

PMID- 19862932
TI  - A bioaugmentation failure caused by phage infection and weak biofilm formation
      ability.
AB  - Two biological aerated filters (BAF) were setup for ammonia removal treatment of
      the circulation water in a marine aquaculture. One of the BAFs was bioaugmented
      with a heterotrophic nitrifying bacterium, Lutimonas sp. H10, where the ammonia
      removal was not improved and the massive inoculation was even followed by a
      nitrification breakdown from day 9 to 18. The nitrification was remained stable
      in control BAF operated under the same conditions. Fluorescent in situ
      hybridization (FISH) with rRNA-targeted probes and cultivable method revealed
      that Lutimonas sp. H10 almost disappeared from the bioaugomented BAF within 3 d,
      and this was mainly due to the infection of a specific phage as revealed by flask
      experiment, plaque assay and transmission electron observation. Analyses of 16S
      rRNA gene libraries showed that bacterial groups from two reactors evolved
      differently and an overgrowth of protozoa was observed in the bioaugmented BAF.
      Therefore, phage infection and poor biofilm forming ability of the inoculated
      strain are the main reasons for bioaugmentation failure. In addition, grazing by
      protozoa of the bacteria might be the reason for the nitrification breakdown in
      bioaugmented BAF during day 9-18.

PMID- 19862933
TI  - Effect of leachate inoculum on biopretreatment of municipal solid waste by a
      combined hydrolytic-aerobic process.
AB  - The biopretreatment of municipal solid waste by a combined hydrolytic-aerobic
      process has become of great interest for biostabilization or biodrying. The study
      aimed at investigating the effect of leachate inoculum on the biopretreatment.
      During the hydrolytic stage, the inoculum addition at the ratio of leachate to
      waste (LWR) of 5% and 7% stimulated the start-up of hydrolysis and enhanced the
      hydrolysis rate by 27.4% and 24.2%, respectively; whereas the inoculation at LWR
      of 1% had almost no effect on the hydrolysis rate and the inoculation at LWR of
      10% reduced the hydrolysis rate by 12.7%. During the subsequent aerobic stage,
      the inoculations at LWRs greater than 5% decreased organics degradation rate. As
      a whole, compared with none inoculation, the total degradation rates of organics
      for inoculating trials at LWRs of 5%, 7% and 10% decreased by 14.5%, 14.3% and
      32.7%, respectively. Correspondingly, their net water removal rates were reduced
      by 4.4%, 5.8% and 19.0%. The inoculation at LWR of 1% could not significantly
      affect the biopretreatment. The inoculum addition at LWR of 5% and 7% could
      shorten hydrolytic stage and thus accelerate the whole combined process.
      Moreover, the inoculations at LWRs greater than 5% were favorable for
      lignocelluloses degradation.

PMID- 19862934
TI  - Neutrophils and asthma.
AB  - Although eosinophilic airway inflammation is recognized as an important feature
      of some patients with chronic, stable asthma, evidence supports an important role
      for neutrophils in asthma. Neutrophils are the first cells recruited to the site
      of the allergic reaction. Their presence may influence clinical presentation and
      has been linked to the development of severe chronic asthma and sudden severe
      attacks. Neutrophils are eliminated by apoptosis during the resolution of the
      allergic response.

PMID- 19862936
TI  - COX-2 inhibition attenuates cough reflex sensitivity to inhaled capsaicin in
      patients with asthma.
AB  - BACKGROUND AND OBJECTIVE: Cyclooxygenase (COX) is an enzyme that converts
      arachidonic acid to prostanoids. There are two isoforms of COX, namely COX-1 and
      COX-2. COX-2 is highly inducible by several stimuli and is associated with
      inflammation. Recent studies have shown that COX-2 is upregulated in the airway
      epithelium of patients with asthma but little is known about the role it plays in
      cough, a common symptom of bronchial asthma. This study was designed to
      investigate the role of COX-2 in cough reflex sensitivity in patients with
      asthma. PATIENTS AND METHODS: The effect of etodolac, a potent COX-2 inhibitor,
      on cough response to inhaled capsaicin was examined in 17 patients with stable
      asthma in a randomized, placebo-controlled crossover study. Capsaicin cough
      threshold, defined as the lowest concentration of capsaicin eliciting 5 or more
      coughs, was measured as an index of airway cough reflex sensitivity. RESULTS: The
      geometric mean (geometric SEM) cough threshold was significantly increased after
      a 2-week treatment program with oral etodolac (200 mg twice a day) compared with
      placebo (36.7 [1.2] vs 21.6 [1.2] gM, P<.02). CONCLUSIONS: These findings
      indicate that COX-2 may be a possible modulator augmenting airway cough reflex
      sensitivity in asthmatic airways.

PMID- 19862935
TI  - Nonsteroidal anti-inflammatory drug hypersensitivity syndrome. A multicenter
      study. I. Clinical findings and in vitro diagnosis.
AB  - BACKGROUND: We present the results obtained from the largest series of in vitro
      diagnostic tests ever reported in patients with clinically validated
      hypersensitivity to acetylsalicylic acid (ASA)/nonsteroidal anti-inflammatory
      drugs (NSAID) compared with various categories of controls tolerating ASA/NSAIDs.
      This multicenter study, which was performed within the framework of the European
      Network for Drug Allergy (ENDA) group, showed that the basophil activation test
      (BAT), particularly when used with the 3 NSAIDs aspirin (ASA), diclofenac (DIC),
      and naproxen (NAP), allows us to confirm the diagnosis of NSAID hypersensitivity
      syndrome. The results of the cellular allergen stimulation test (CAST) frequently
      correlate with those of the BAT, although not always. An unexpected finding was
      that basophil activation by NSAIDs is not an all-or-nothing phenomenon restricted
      to clinically hypersensitive patients, but that it also occurs in a dose-related
      manner in some NSAID-tolerant control individuals.Therefore, NSAID
      hypersensitivity appears as a shift in the normal pharmacological response to
      NSAIDs. These findings allow us to formulate a new rational hypothesis about the
      mechanism of NSAID hypersensitivity syndrome, a mechanism that most authors
      continue to describe as "unknown." METHODS: We enrolled 152 patients with a
      history of hypersensitivity to NSAIDs and 136 control participants in 11
      different centers between spring 2003 and spring 2006. Flowcytometric BAT was
      performed. RESULTS: The most noteworthy results of our study were that 57% of 140
      patients presented very clear-cut positive BAT results to multiple NSAIDs, and
      16% were entirely negative. In about 27% of cases, positive results were obtained
      with 1 or 2 concentrations of a single NSAID. There is clearly a correlation
      between the results of BAT and CAST. CONCLUSIONS: BAT seems particularly
      indicated in patients with a clinical history of NSAID intolerance, and in whom a
      provocation test is not advisable for ethical, clinical, or other reasons. Clear
      cut positive results can be considered as confirming a history of NSAID
      hypersensitivity, although negative results may not exclude it.

PMID- 19862937
TI  - The A-444C polymorphism in the leukotriene C4 synthase gene is associated with
      aspirin-induced urticaria.
AB  - BACKGROUND: Cysteinyl leukotriene production seems to be dysregulated in patients
      with hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs
      (NSAIDs). However, the underlying pathogenic mechanisms of these reactions are
      poorly understood. Previous studies have suggested a role for the A-444C
      polymorphism on the leukotriene C4 synthase gene (LTC4S) in aspirin-induced
      urticaria (AIU), but the results are controversial. OBJECTIVE: To evaluate in a
      case-control study whether the A-444C polymorphism in the promoter region of
      LTC4S is associated with AIU and atopic phenotypes in a Venezuelan population.
      METHODS: One hundred ten patients with AIU and 165 nonallergic controls were
      included. AIU was diagnosed by clinical history and confirmed by double-blind
      placebo-controlled oral provocation tests with NSAIDs. Genotyping of A-444C was
      performed by real-time polymerase chain reaction using Taqman probes. Atopy was
      defined as a positive skin test result to any of the 25 aeroallergens tested.
      Total and mite-specific immunoglobulin (Ig) E levels in serum were quantified
      using an enzyme-linked immunosorbent assay RESULTS: A-444C was associated with
      AIU. The C allele was more frequent in patients with the cutaneous pattern of AIU
      and in patients with low skin reactivity to histamine. There was no association
      between A-444C and asthma, atopy, or total IgE levels. CONCLUSION: The C allele
      of the A-444C polymorphism is a risk factor for AIU in our population and could
      be a genetic marker for this phenotype. Furthermore, this single-nucleotide
      polymorphism is mainly associated with the cutaneous clinical pattern and with
      low skin response to histamine.

PMID- 19862938
TI  - High prevalence of asthma and allergic diseases in children aged 6 to [corrected]
      7 years from the Canary Islands. [corrected].
AB  - OBJECTIVE: To investigate the prevalence of bronchial asthma and allergic
      diseases in schoolchildren from the Canary Islands, Spain. METHODS: Cross
      sectional study following the methodology of ISAAC (International Study of Asthma
      and Allergies in Childhood), which uses standardized and validated
      questionnaires. The study participants were children aged between 6 and 7 years
      attending schools in Las Palmas de Gran Canaria, Canary Islands, Spain. RESULTS:
      Of the 3108 questionnaires distributed, 1883 were answered, and 1871 were
      evaluable (60.6%). Gender distribution was similar (51.8% boys vs 48.2% girls).
      Current prevalence of asthma was 18.4% (95% confidence interval [CI], 16.7-20.2),
      rhinitis 40.3% (95% CI, 38-42.3), and atopic dermatitis 35.8% (95% CI, 33.6
      37.9). The highest prevalence of rhinitis was recorded during the autumn months
      (P<.005). Asthma was more frequent in boys than in girls (P<.05), but there were
      no statistical differences for the other allergic diseases. CONCLUSIONS: The
      prevalence of asthma and allergic diseases in children aged 6-7 years in the
      Canary Islands is higher than in other areas of Spain where the ISAAC study has
      been performed. Male gender is an important risk factor in children, especially
      for asthma symptoms.

PMID- 19862939
TI  - Single-nucleotide polymorphisms in genes predisposing to asthma in children of
      Chinese Han nationality.
AB  - BACKGROUND: Research increasingly suggests that asthma is a familial and
      hereditary disorder in the pathogenesis of which genetic and environmental
      factors play an important role. OBJECTIVE: To investigate the single and combined
      associations between 8 single-nucleotide polymorphism (SNP) loci in 5 genes and
      the development of asthma in children of Chinese Han nationality. METHODS: The
      study population comprised 192 children with asthma and an equal number of
      healthy controls. Asthma was diagnosed in accordance with American Thoracic
      Society criteria. Polymerase chain reaction-restriction fragment length
      polymorphism was used to detect the genotypes of the SNP loci. RESULTS: No
      statistically significant differences (P>.05) were found between the experimental
      and control group in genotype distribution among 6 loci (IL-13 C- 1112T, IL-13
      C1923T, IL-4 C-590T, IL-4RA 175V, FcepsilonR1beta E237G, and beta2-ADR Q27E).
      However, significant diversity was observed among FcepsilonR1beta C-109T (P=.002)
      and beta2-ADR R16G (P=.000). Furthermore, the frequency of FcepsilonR1beta C-109T
      T/T and beta2-ADR R16G A/A in the asthma group was significantly higher than in
      the control group (odds ratio [OR]=1.96, P=.001; OR=2.58, P=.000, respectively).
      Carriers of both FcepsilonR1beta C-109T T/T and beta2-ADR R16G A/A had a more
      significant risk of developing asthma than those with only a single polymorphism.
      CONCLUSION: The 6 loci (IL-13 C-1112T, IL-13 C1923T, IL-4 C-590T, IL-4RA 175V,
      FcER1B E237G and 12-ADR Q27E) make little contribution to the development of
      asthma in children of Chinese Han nationality. FcepsilonR1beta C-109T and beta2
      ADR R16G are significantly associated with childhood asthma. FcepsilonR1beta C
      109T T/T and beta2-ADR R16G A/A have a significant and combined effect on the
      development of asthma.

PMID- 19862940
TI  - Reference values for facilitating the interpretation of the ESPRINT-15
      questionnaire (Spanish version).
AB  - OBJECTIVE: ESPRINT-15 is a specific, short-form instrument to measure health
      related quality of life in adults suffering from allergic rhinitis. The aim of
      this study was to obtain reference values in order to improve its
      interpretability. METHODS: ESPRINT-15 was administered to a representative sample
      of Spanish adults with allergic rhinitis. Means and percentiles were obtained,
      taking into account the kind of rhinitis (persistent/intermittent) and symptom
      severity (very mild/mild/moderate/severe). RESULTS: A total of 2756 patients
      participated in the study. Mean (SD) scores were significantly lower (better) for
      men than for women (2.2 [1.4] vs 2.4 [1.4], P<.001, effect size [ES] is congruent
      to 0.15). Patients with intermittent rhinitis showed better scores than patients
      with persistent rhinitis (2.1 [1.4] vs. 2.5 [1.4], P<.001, ES is congruent to
      0.21). Mean (SD) scores were higher (worse) when severity of symptoms increased,
      ranging from 0.9 (0.9) (very mild) to 3.7 (1.0) (severe) (ES is congruent to 1.0
      between each consecutive group of symptom severity). CONCLUSIONS: The magnitude
      of the differences found among groups of patients reinforces the usefulness of
      providing reference values stratified by gender, type of allergic rhinitis, and
      symptom severity. The percentiles obtained can be used in clinical practice to
      evaluate individual scores, and assign the patient to the corresponding reference
      group.

PMID- 19862941
TI  - Itraconazole, an effective adjunctive treatment for allergic bronchopulmonary
      aspergillosis.
AB  - We report the case of a 21-year old man with a long-standing history of severe
      asthma and allergic rhinosinusitis who developed progressive worsening of
      dyspnea, wheezing, productive cough, and nasal obstruction, with little response
      to antibiotics and repeated short courses of oral corticosteroids. A diagnosis of
      allergic bronchopulmonary aspergillosis was made on the basis of a combination of
      clinical, laboratory and radiographic findings.Treatment with oral
      methylprednisolone and itraconazole resulted in an improvement in symptoms, lung
      function and computed tomography results, as well as in a decrease in total serum
      immunoglobulin E. This case report highlights the importance of a high degree of
      clinical suspicion in order to diagnose and treat allergic bronchopulmonary
      aspergillosis in patients with a long-standing history of severe asthma as early
      as possible as this has a major impact on prognosis. It also highlights the
      effectiveness of itraconazole as adjunctive therapy to systemic corticosteroids
      in this condition.

PMID- 19862942
TI  - Selective allergy to lobster in a case of primary sensitization to house dust
      mites.
AB  - Allergy to only 1 kind of seafood is uncommon. We report a case of selective
      allergy to lobster. We studied a 30-year-old man who suffered generalized
      urticaria, facial erythema, and pharyngeal pruritus after eating lobster. He had
      a more than 10-year history of mild persistent asthma and sensitization to house
      dust mites. The study was performed by skin prick test, and prick-prick test,
      oral food challenge, specific immunoglobulin (Ig) E determinations by CAP
      (Phadia, Uppsala, Sweden) and ADVIA-Centaur (ALK-Abello, Madrid, Spain), and IgE
      immunoblotting. The patient's serum recognized 2 allergens of around 198 kDa and
      2 allergens of around 65 kDa from the lobster extract, allergens of around 15,
      90, and 120 kDa from Dermatophagoides pteronyssinus extract, and allergens of
      around 15 and 65 kDa from Dermatophagoides farinae extract. Serum did not
      recognize purified shrimp tropomyosin. Immunoblot-inhibition assay results
      indicated cross-reactivity between lobster and mite allergens. This is the first
      report of selective allergy to lobster.

PMID- 19862943
TI  - Compound allergy to an antihemorrhoidal ointment demonstrated by the repeated
      open application test.

PMID- 19862944
TI  - Photoallergic contact dermatitis due to isoamyl-p-methoxycinnamate.

PMID- 19862945
TI  - Successful treatment of allergic bronchopulmonary candidiasis with a recombinant
      anti-immunoglobulin E antibody.

PMID- 19862946
TI  - Use of a short messaging service system to provide information about airborne
      pollen concentrations and forecasts.

PMID- 19862947
TI  - Immediate hypersensitivity to latex in the absence of demonstrable specific
      immunoglobulin E.

PMID- 19862948
TI  - Anaphylaxis to mango fruit and crossreactivity with Artemisia vulgaris pollen.

PMID- 19862949
TI  - Biodegradation of polycyclic aromatic hydrocarbons in sediments from the Daliao
      River watershed, China.
AB  - The Daliao River, as an important water system in Northeast China, was reported
      to be heavily polluted by polycyclic aromatic hydrocarbons (PAHs). Aerobic
      biodegradations of four selected PAHs (naphthalene, phenanthrene, fluorene and
      anthracene) alone or in their mixture in river sediments from the Daliao River
      water systems were studied in microcosm systems. Effects of additional carbon
      source, inorganic nitrogen and phosphorus, temperature variation on PAHs
      degradation were also investigated. Results showed that the degradation of
      phenanthrene in water alone system was faster than that in water-sediment
      combined system. Degradation of phenanthrene in sediment was enhanced by adding
      yeast extract and ammonium, but retarded by adding sodium acetate and not
      significantly influenced by adding phosphate. Although PAHs could also be
      biodegraded in sediment under low temperature (5 degrees C), much lower
      degradation rate was observed. Sediments from the three main streams of the
      Daliao River water system (the Hun River, the Taizi River and the Daliao River)
      demonstrated different degradation capacities and patterns to four PAHs. Average
      removal rates (15 or 19 d) of naphthalene, phenanthrene, fluorene and anthracene
      by sediment were in the range of 0.062-0.087, 0.005-0.066, 0.008-0.016 and 0
      0.059 mg/(L x d), respectively. As a result, naphthalene was most easily degraded
      compound, anthracene was the hardest one. In multiple PAHs systems, the
      interactions between PAHs influenced each PAH biodegradation.

PMID- 19862950
TI  - Enhanced removal of organics by permanganate preoxidation using tannic acid as a
      model compound--role of in situ formed manganese dioxide.
AB  - The effect of permanganate preoxidation on organic matter removal during the
      coagulation with aluminum chloride was investigated using tannic acid as a model
      compound. Results showed that a small amount of KMnO4 (0.75 mg/L) increased the
      removal efficiency of tannic acid up to 20%, as compared to the process of
      coagulation by aluminum chloride alone. The key factor enhancing the removal
      efficiency of tannic acid in preoxidation process was the in situ formation of a
      reductant manganese dioxide. The complexation model was used to describe the
      reaction between MnO2 and tannic acid. Under weak pH condition, tannic acid was
      difficult to be adsorbed by MnO2 due to the static electrical repulsive forces.
      The presence of Ca2+ served as a bridge to hold the negative charged MnO2 and
      tannic acid together, which could be a crucial factor influencing tannic acid
      adsorption by in-situ manganese dioxide.

PMID- 19862951
TI  - In-situ stabilisation followed by ex-situ composting for treatment and disposal
      of heavy metals polluted sediments.
AB  - An innovative in-situ stabilisation treatment followed by ex-situ sediment
      composting was tested for its ability to treat and dispose of heavy-metal
      polluted sediments in a river near the Chinese Pearl Delta. First, polluted
      sediments were treated in-situ to stabilise the heavy metals. Then the treated
      sediments were dredged, dewatered and sent for high temperature aerobic
      composting (HTAC) treatment. Finally, the compost products were used as a
      fertiliser for river bank plants. The stabilisation efficiency of heavy metals
      during the process was investigated and the results are as follows: (1) using in
      situ stabilisation, the extraction concentrations of Cu, Zn and Pb were reduced
      by 65.0%, 82.2% and 90.0%, respectively, which are much lower than the national
      standard given in the Identification Standard for Hazardous Waste (GB5085.3
      1996); (2) chemical fraction analysis showed that heavy metals were further
      stabilized during the HTAC treatment; (3) the concentrations of Cu, Zn and Pb in
      rainwater leachate through the river bank met the level of class V in the
      Environmental Quality Standards for Surface Water in China (GB3838-2002).
      Therefore, using this new process, the toxicities of heavy metals in sediments
      were reduced markedly.

PMID- 19862952
TI  - Adsorption characteristics of humic acid-immobilized amine modified
      polyacrylamide/bentonite composite for cationic dyes in aqueous solutions.
AB  - Humic acid-immobilized amine modified polyacrylamide/bentonite composite (HA-Am
      PAA-B) was prepared and used as an adsorbent for the adsorption of cationic dyes
      (Malachite Green (MG), Methylene Blue (MB) and Crystal Violet (CV)) from aqueous
      solutions. The polyacrylamide/bentonite composite (PAA-B) was prepared by
      intercalative polymerization of acrylamide with Na-bentonite in the presence of
      N,N'-methylenebisacrylamide as a crosslinking agent and hexamethylenediammine as
      propagater. PAA-B was subsequently treated with ethylenediammine to increase its
      loading capacity for HA. The surface characterizations of the adsorbent were
      investigated. The adsorbent behaved like a cation exchanger and more than 99.0%
      removal of dyes was detected at pH range 6.0-8.0. The capacity of HA-Am-PAA-B was
      found to decrease in the following order: MG > MB > CV. The kinetic and isotherm
      data were interpreted by pseudo-second order rate equation and Freundlich
      isotherm model, respectively. Experiments were carried out using binary solute
      systems to assess the competitive adsorption phenomenon. The experimental
      isotherm data for each binary solute combination of MG, MB and CV were analyzed
      using Sheindrof-Rebhun-Sheintuch (SRS) (multicomponent Freundlich type) equation.

PMID- 19862954
TI  - Profile and removal of endocrine disrupting chemicals by using an ER/AR
      competitive ligand binding assay and chemical analyses.
AB  - An estrogen receptor (ER)/androgen receptor (AR) ligand competitive binding assay
      (ER/AR-binding assay) and chemical analyses were used to evaluate the endocrine
      disrupting chemicals (EDCs) behavior of two municipal wastewater treatment plants
      (WWTPs) (K and S). In the influents, estrone (E1), androsterone (A),
      androstenedione (AD), BPA (bisphenol A), NP (nonylphenol) and daidzein (DZ) were
      detected in high amounts with subsequent 24 h-average concentrations of 350,
      1000, 29, 1300, 3900, and 5700 ng/L in K-WWTP and of 310, 620, 59, 1600, 2600,
      and 8400 ng/L in S-WWTP. The estrogenic (androgenic) activity as 17beta-estradiol
      (E2) equivalents (EEQ) or testosterone (Te) equivalents (TEQ) was consequently
      620 ng E2/L (570 ng Te/L) and 580 ng E2/L (800 ng Te/L) for the two WWTPs. The
      removal efficiencies of the above mentioned sole target chemicals were 51%-100%
      for K-WWTP and 55.6%-100% for S-WWTP. The removal efficiencies of EEQ were about
      73% for both WWTPs, while the removal efficiencies of TEQ were 62.1% for K-WWTP
      and 98.4% for S-WWTP. In addition, chemical-derived EEQ were about 1.2%-52.4% of
      those by ER-binding assay for K-WWTP and the corresponding ratios were 1.3%-83.3%
      for S-WWTP, while chemical derived TEQ were less than 3% of values measured by
      the AR-binding assay for both WWTPs.

PMID- 19862953
TI  - Seasonal variation of Microcystis in Lake Taihu and its relationships with
      environmental factors.
AB  - In order to monitor the changes of Microcystis along with temporal and spatial
      variations, seasonal variation of Microcystis in Lake Taihu was investigated by
      16S-23S rRNA internal transcribed spacer denaturing gradient gel electrophoresis
      (16S-23S rRNA-ITS DGGE) and microscopic evaluation. Samples were collected
      quarterly at four sites (River Mouth, Meiliang Bay, Cross Area, and Lake Center)
      from August 2006 to April 2007. Results showed that Microcystis dominated total
      phytoplankton abundance at the four sites in all seasons except winter. The
      average annual abundance of Microcystis was relatively high at River Mouth and
      Meiliang Bay, reaching 81.22 x 10(6) and 61.32 x 10(6) cells/L, respectively. For
      temporal variations, Shannon-Wiener diversity index (H') according to DGGE
      profile revealed the richness of Microcystis in summer (H' = 1.375 +/- 0.034) and
      winter (H' = 1.650 +/- 0.032) was lower than that in spring (H' = 2.078 +/-
      0.031) and autumn (H' = 2.365 +/- 0.032) (P <0.05). While for spatial variations,
      the richness of Microcystis at River Mouth (H' = 2.015 +/- 0.074) was higher than
      at other sites during four seasons (P < 0.01). Very few differences of
      Microcystis diversity in the same season were observed among the other three
      sites (P > 0.05). Canonical correspondence analysis (CCA) was performed to
      elucidate the relationships between Microcystis operational taxonomic units
      (OTUs) composition and the environmental factors. Results of CCA revealed that
      temperature was strongly positively correlated with the first axis (r = 0.963),
      while TSS was negative correlated with the second axis (r = -0.716). Phylogenetic
      tree based on the sequencing results of target bands on DGGE gel indicated that
      samples collected in summer and winter constituted two separated clusters.

PMID- 19862955
TI  - Removal characteristics of CO2 using aqueous MEA/AMP solutions in the absorption
      and regeneration process.
AB  - The carbon dioxide (CO2) removal efficiency, reaction rate, and CO2 loading into
      aqueous blended monoethanolamine (MEA) + 2-amino-2-methyl-1-propanol (AMP)
      solutions to enhance absorption characteristics of MEA and AMP were carried out
      by the absorption/regeneration process. As a result, compared to aqueous MEA and
      AMP solutions, aqueous blended MEA + AMP solutions have a higher CO2 loading than
      MEA and a higher reaction rate than AMP. The CO2 loading of rich amine of aqueous
      18 wt.% MEA + 12 wt.% AMP solution was 0.62 mol CO2/mol amine, which is 51.2%
      more than 30 wt.% MEA (0.41 mol CO2/mol amine). Consequently, blending MEA and
      AMP could be an effective way to design considering economical efficiency and
      used to operate absorber for a long time.

PMID- 19862956
TI  - Seasonal features of aerosol particles recorded in snow from Mt. Qomolangma
      (Everest) and their environmental implications.
AB  - To assess the seasonality of aerosol deposition and anthropogenic effects on
      central Himalayas, a 1.85-m deep snow pit was dug on the northern slope of Mt.
      Qomolangma (Everest). Based on the morphology and energy dispersive X-ray (EDX)
      signal, totally 1500 particles were classed into 7 groups: soot;
      aluminosilicates; fly ash; calcium sulfates; Ca/Mg carbonates; metal oxides; and
      biological particles and carbon fragments. The size distribution and number
      fractions of different particle groups exhibited distinct seasonal variations
      between non-monsoon and monsoon periods, which are clearly related to the
      differences in air mass pathways. Specifically, the relative abundance of soot in
      non-monsoon period (25%) was much higher than that in monsoon period (14%),
      indicating Mt. Qomolangma region received more anthropogenic influence in non
      monsoon than monsoon period.

PMID- 19862957
TI  - Effects of maize root exudates and organic acids on the desorption of
      phenanthrene from soils.
AB  - The effects of maize root exudates and low-molecular-weight-organic anions
      (LMWOAs) on the desorption of phenanthrene from eight artificially contaminated
      soils were evaluated. A significant negative correlation was observed between the
      amounts of phenanthrene desorbed and the soil organic carbon (SOC) contents (P <
      0.01), and the influences of soil pH and clay content on phenanthrene desorption
      were insignificant (P > 0.1). Neither maize root exudates nor oxalate and citrate
      anions influenced desorption of phenanthrene with the addition of NaN3. A faster
      phenanthrene desorption occurred without the addition of NaN3 in the presence of
      maize root exudates than oxalate or citrate due to the enhanced degradation by
      root exudates. Without the addition of NaN3, oxalate or citrate at different
      concentrations could inhibit phenanthrene desorption to different extents and the
      inhibiting effect by citrate was more significant than by oxalate. This study
      leads to the conclusion that maize root exudates can not enhance the desorption
      under abiotic condition with the addition of NaN3 and can promote the desorption
      of phenanthrene in soils without the addition of NaN3.

PMID- 19862959
TI  - Agricultural non-point nitrogen pollution control function of different
      vegetation types in riparian wetlands: a case study in the Yellow River wetland
      in China.
AB  - Riparian wetland is the major transition zone of matter, energy and information
      transfer between aquatic and terrestrial ecosystems and has important functions
      of water purification and non-point pollution control. Using the field experiment
      method and an isotope tracing technique, the agricultural non-point nitrogen
      pollution control function of different vegetation types in riparian wetland was
      studied in the Kouma Section of the Yellow River. The results showed that the
      retention of agricultural non-point nitrogen pollution by riparian wetland soil
      occurs mainly in top 0-10 cm layer. The amount of nitrogen retained by surface
      soils associated with three types of vegetation are 0.045 mg/g for Phragmites
      communis Trin Linn, 0.036 mg/g for Scirpus triqueter Linn, and 0.032 mg/g for
      Typha angustifolia Linn, which account for 59.21%, 56.25%, and 56.14% of the
      total nitrogen interception, respectively. Exogenous nitrogen in 0-10 cm soil
      layer changes more quickly than in other layers. One month after adding K(15)NO3
      to the tested vegetation, nitrogen content was 77.78% for P. communis Trin,
      68.75% for T. angustifolia, and 8.33% for S. triqueter in the surface soil. After
      three months, nitrogen content was 93.33% for P. communis Trin, 72.22% for S.
      triqueter, and 37.50% for T. Angustifolia. There are large differences among
      vegetation communities respecting to purification of agricultural non-point
      nitrogen pollution. The nitrogen uptake amount decreases in the sequence: new
      shoots of P. communis Trin (9.731 mg/g) > old P. communis Trin (4.939 mg/g) > S.
      triqueter (0.620 mg/g) > T. angustifolia (0.186 mg/g). Observations indicated
      that the presence of riparian wetlands as buffers on and adjacent to stream banks
      could be recommended to control agricultural non-point pollution.

PMID- 19862958
TI  - Effect of ionic strength on adsorption of As(III) and As(V) on variable charge
      soils.
AB  - The study was to investigate the adsorption behavior of arsenite (As(III)) and
      arsenate (As(V)) on two variable charge soils, i.e., Haplic Acrisol and Rhodic
      Ferralsol at different ionic strengths and pH with batch methods. Results
      indicated that the amount of As(III) adsorbed by these two soils increased with
      increasing solution pH, whereas it decreased with increasing ionic strength under
      the acidic condition. This suggested that As(III) was mainly adsorbed on soil
      positive charge sites through electrostatic attraction under the acidic
      condition. Moreover, intersects of As(V) adsorption-pH curves at different ionic
      strengths (a characteristic pH) are obtained for both soils. It was noted that
      above this pH, the adsorption of As(V) was increased with increasing ionic
      strength, whereas below it the reverse trend was true. Precisely the intersect pH
      was 3.6 for Haplic Acrisol and 4.5 for Rhodic Ferralsol, which was near the
      values of PZSE (soil point of zero salt effect) of these soils. The effects of
      ionic strength and pH on arsenate adsorption by these soils were interpreted by
      the adsorption model. The results of zeta potential suggested that the potential
      in adsorption plane becomes less negative with increasing ionic strength above
      soil PZSE and decreases with increasing ionic strength below soil PZSE. These
      results further supported the hypothesis of the adsorption model that the
      potential in the adsorption plane changes with ionic strength with an opposite
      trend to surface charge of the soils. Therefore, the change of the potential in
      the adsorption plane was mainly responsible for the change of arsenate adsorption
      induced by ionic strength on variable charge soils.

PMID- 19862960
TI  - Variation of peroxidase isoenzyme and biofilm of Phanerochaete chrysosporium in
      continuous membrane bioreactor for reactive Brilliant Red X3-B treatment.
AB  - The influence of a Reactive Brilliant Red X-3B (RBR X-3B) dye on the peroxidase
      isoenzyme of Phanerochaete chrysosporium was determined, and the biofilm
      structure in a white rot fungal continuous membrane bioreactor (MBR) was also
      investigated by scanning electron microscope (SEM). The variation of peroxidase
      isoenzyme and the decolorization rate in the continuous MBR were evaluated. The
      results showed that the 100 mg/L RBR X-3B could stimulate the production of the
      peroxidase isoenzyme in the shaking-flask culture. In addition, two new
      peroxidase isoenzyme bands with relative mobility (Rf) value of 0.27 and 0.28
      appeared, but the activity was lower than the blank control of 11 d. In the
      continuous MBR, the system worked stably during the first 60 d, the main
      peroxidase isoenzyme bands existed and three new bands with Rf value of 0.10,
      0.27, and 0.28 appeared. Meanwhile, the biofilm grew well and the average
      decolorization rate could reach 90.6%. But the bands of peroxidase isoenzyme
      decreased rapidly at day 65, only two bands with Rf value 0.24 and 0.26 existed,
      and the decolorization rate decreased to 78.3%. Therefore, 5 bottles of P.
      chrysosporium mycelial pellet were added into the MBR, and then the activity of
      the peroxidase isoenzyme and the decolorization rate had a slight recovery.
      Finally, the decolorization rate finally decreased to 75.2%. These results
      contribute to a comprehensive understanding of the variation of peroxidase
      isoenzyme and biofilm in continuous MBR by white rot fungi.

PMID- 19862961
TI  - Bioaccumulation of hexachlorobenzene in Eisenia foetida at different aging
      stages.
AB  - The impacts of contact time on the extractability, the availability of
      hexachlorobenzene (HCB) in different soils (paddy soil, red soil, and fluvo-aquic
      soil) and bioaccumulation in earthworm Eisenia foetida were investigated under
      controlled conditions in laboratory. Results indicated that the aging rate of HCB
      displaying a biphasic character in different soils: a rapid aging in the first 60
      d followed by a slow aging in the next 120 d incubation time. Moreover, most of
      extractable HCB (about 90%) decline occurred in the first 60 d after HCB was
      spiked into the soils. The aging rate of HCB in the paddy soil was higher than
      that in the fluvo-aquic soil or the red soil. The amount of HCB accumulated in
      the earthworms and its accumulative ability, expressed as a bioaccumulation
      factor (BAF), declined as the aging time increased from 1 to 180 d. Although the
      extractable HCB decreased with increasing residence time in soil, much of HCB
      could still be accumulated by earthworms (457.6-984.3 ng/g) through
      bioaccumulation, which poses a potential risk to soil ecological safety.

PMID- 19862962
TI  - Influence of oxytetracycline on the structure and activity of microbial community
      in wheat rhizosphere soil.
AB  - The microbial community composition in wheat rhizosphere was analyzed by
      detecting colony forming units (CFUs) in agar plates. The total CFUs in
      rhizosphere were 1.04 x 10(9)/g soil with 9.0 x 10(8)/g bacteria, 1.37 x 10(8)/g
      actinomyces and 3.6 x 10(6)/g fungi. The 10 dominant bacteria were isolated from
      wheat rhizosphere and were grouped into genus Bacillus according to their full
      length 16S rRNA gene sequences. Although belonging to the same genus, the
      isolated strains exhibited different sensitivities to oxytetracycline. When a
      series of the rhizosphere soil was exposed under various concentrations of
      oxytetracycline, the microbial community structure was highly affected with
      significant decline of CFUs of bacteria and actinomyces (22.2% and 31.7% at 10
      mg/kg antibiotic, respectively). This inhibition was clearly enhanced with the
      increase exposure dosage of antibiotic and could not be eliminated during 30 d
      incubation. There was no obvious influence of this treatment on fungi population.
      Among the four soil enzymes (alkaline phosphatase, acidic phosphatase,
      dehydrogenase and urease), only alkaline phosphatase was sensitive to
      oxytetracycline exposure with 41.3% decline of the enzyme activity at 10 mg/kg
      antibiotic and further decrease of 64.3%-80.8% when the dosage over 30 mg/kg.

PMID- 19862963
TI  - Isolation and characterization of Pseudomonas otitidis WL-13 and its capacity to
      decolorize triphenylmethane dyes.
AB  - Pseudomonas otitidis WL-13, which has a high capacity to decolorize
      triphenylmethane dyes, was isolated from activated sludge obtained from a
      wastewater treatment plant of a dyeing industry. This strain exhibited a
      remarkable color-removal capability when tested against several triphenylmethane
      dyes under both shaking and static conditions at high concentrations of dyes.
      More than 95% of Malachite Green and Brilliant Green was removed within 12 h at
      500 micromol/L dye concentration under shaking conditions. Crystal Violet lost
      about 13% of its color under the same conditions tested. The rate of
      decolorization increased when the M9 medium was supplemented with yeast extract.
      The optimum pH and temperature for color removal were 7-9 and 35-40 degrees C,
      respectively. The observed changes in the visible spectra and the inspection of
      bacterial growth indicated the color-removal by the adsorption of dye to the
      cells during incubation with strains.

PMID- 19862964
TI  - Combination effect of pH and acetate on enzymatic cellulose hydrolysis.
AB  - The productivity and efficiency of cellulase are significant in cellulose
      hydrolysis. With the accumulation of volatile fatty acids (VFAs), the pH value in
      anaerobic digestion system is reduced. Therefore, this study will find out how
      the pH and the amount of acetate influence the enzymatic hydrolysis of cellulose.
      The effects of pH and acetate on cellulase produced from Bacillus coagulans were
      studied at various pH 5-8, and acetate concentrations (0-60 mmol/L). A batch
      kinetic model for enzymatic cellulose hydrolysis was constructed from
      experimental data and performed. The base hypothesis was as follows: the rates of
      enzymatic cellulose hydrolysis rely on pH and acetate concentration. The results
      showed that the suitable pH range for cellulase production and cellulose
      hydrolysis (represents efficiency of cellulase) was 2.6-7.5, and 5.3-8.3,
      respectively. Moreover, acetate in the culture medium had an effect on cellulase
      production (K(I) = 49.50 mmol/L, n = 1.7) less than cellulose hydrolysis (K(I) =
      37.85 mmol/L, n = 2.0). The results indicated that both the pH of suspension and
      acidogenic products influence the enzymatic hydrolysis of cellulose in an
      anaerobic environment. To enhance the cellulose hydrolysis rate, the accumulated
      acetate concentration should be lower than 25 mmol/L, and pH should be maintained
      at 7.

PMID- 19862965
TI  - Induction of chemotaxis to sodium chloride and diacetyl and thermotaxis defects
      by microcystin-LR exposure in nematode Caenorhabditis elegans.
AB  - Apart from the liver disruption, embryotoxicity and genotoxicity, microcystin
      (MC)-LR also could cause neurotoxicity. Nematode Caenorhabditis elegans was
      explored as a model to study the neurotoxicity. In the present study, we provided
      evidence to indicate the neurotoxicity on chemotaxis to NaCl and diacetyl, and
      thermotaxis from MC-LR exposure to C. elegans. As a result, higher concentrations
      of MC-LR caused significantly severe defects of chemotaxis to NaCl and diacetyl,
      and thermotaxis. The neurotoxicity on chemotaxis to NaCl and diacetyl, and
      thermotaxis from MC-LR exposure might be largely mediated by the damage on the
      corresponding sensory neurons (ASE, AWA, and AFD) and interneuron AIY The
      expression levels of che-1 and odr-7 were significantly decreased (P < 0.01) in
      animals exposed to MC-LR at concentrations lower than 10 microg/L, whereas the
      expression levels of ttx-1 and ttx-3 could be significantly (P < 0.01) lowered in
      animals even exposed to 1 microg/L of MC-LR. Moreover, both the chemotaxis to
      NaCl and diacetyl and the thermotaxis were more significantly reduced in MC-LR
      exposed mutants of che-1(p674), odr-7(ky4), ttx-1(p767), and ttx-3(ks5) than
      those in exposed wild-type N2 animals at the same concentrations.

PMID- 19862966
TI  - Cadmium bioaccumulation in three benthic fish species, Salaria basilisca,
      Zosterisessor ophiocephalus and Solea vulgaris collected from the Gulf of Gabes
      in Tunisia.
AB  - To select a marine teleost fish which can be used as a bioindicator of cadmium
      (Cd) pollution in the Gulf of Gabes in Tunisia, Cd concentrations in liver and
      gill were compared in three benthic fish species including Salaria basilisca,
      Zosterisessor ophiocephalus and Solea vulgaris. Fish samples were collected from
      three selected sites in the Gulf of Gabes, with different degrees of Cd
      contamination: the industrialized coast of Sfax (S1), the coast of Douar Chatt
      (S2) and the coast of Luza (S3). The results shows that Cd concentrations in both
      sediment and water collected from S1 were significantly higher (p < 0.0001) than
      those from S2 and S3. For each species, Cd concentrations, in both liver and
      gill, showed the decreasing order: S1 > S2 > S3. The highest concentration of Cd
      was detected in the liver of S. basilisca, and only S. basilisca showed
      bioaccumulation factors (BAF) greater than 1 in all studied sites. In S1 and S2,
      BAF values respect the following order: S. basilisca > Z. ophiocephalus > S.
      vulgaris. These results of significant bioaccumulation of Cd, in terms of hepatic
      concentrations and bioaccumulation factors, indicated that S. basilisca can be
      used as bioindicator to evaluate the evolution of Cd pollution in the Gulf of
      Gabes.

PMID- 19862967
TI  - In situ adsorption-catalysis system for the removal of o-xylene over an activated
      carbon supported Pd catalyst.
AB  - An activated carbon (AC) supported Pd catalyst was used to develop a highly
      efficient in situ adsorption-catalysis system for the removal of low
      concentrations of o-xylene. In this study, three kinds of Pd/AC catalysts were
      prepared and tested to investigate the synergistic efficiency between adsorption
      and catalysis for o-xylene removal. The Pd/AC catalyst was first used as an
      adsorbent to concentrate dilute o-xylene at low temperature. After saturated
      adsorption, the adsorbed o-xylene was oxidized to CO2 and H2O by raising the
      temperature of the catalyst bed. The results showed that more than 99% of the
      adsorbed o-xylene was completely oxidized to CO2 over a 5% Pd/AC catalyst at 140
      degrees C. Brunauer-Emmett-Teller (BET) analysis, scanning electron microscopy
      (SEM), temperature-programmed desorption (TPD), and temperature-programmed
      oxidation (TPO) were applied to investigate the physical properties of o-xylene
      adsorption-desorption and the in situ adsorption-catalysis activity of the AC
      support and Pd/AC catalyst. A synergistic relationship between the AC support and
      the active Pd species for the removal of low concentrations of o-xylene was
      established.

PMID- 19862968
TI  - Photocatalytic degradation of methyl orange over ITO/Cds/ZnO interface composite
      films.
AB  - ITO/CdS/ZnO interface composite films were successfully prepared by subsequent
      electrodeposition of CdS and ZnO onto indium tin oxide (ITO) glass substrates.
      The obtained ITO/CdS/ZnO composite films were characterized with X-ray
      diffraction (XRD), scanning electron microscopy (SEM), and UV-Vis spectroscopy.
      The photocatalytic activity of ITO/CdS/ZnO composite films were investigated
      using methyl orange (MO) as a model organic compound under UV light irradiation.
      The influence of operating parameters on MO degradation including initial
      concentration of MO, pH value of solution, and inorganic anion species over the
      composite films were examined. A blue shift of absorption threshold was observed
      for the ITO/CdS/ZnO film in comparison with ITO/ZnO film. ITO/CdS/ZnO composite
      films prepared under specific conditions showed a higher photocatalytic activity
      than that of ITO/ZnO films. It was also found that the photocatalytic degradation
      of MO on the composite films followed pseudo-first order kinetics.

PMID- 19862969
TI  - Photocatalytic performance of TiO2 catalysts modified by H3PW12O40, ZrO2 and
      CeO2.
AB  - The binary composite photo-catalysts CeO2/TiO2, ZrO2/TiO2 and the ternary
      composite photo-catalysts H3PW12O40-CeO2/TiO2, H3PW12O40-ZrO2/TiO2 were prepared
      by sol-gel method. The catalysts were characterized by thermogravimetric
      differential thermal analysis (TG-DTA), scanning electron microscopy (SEM) and X
      ray diffraction (XRD). The photocatalytic elimination of methanol was used as
      model reaction to evaluate the photocatalytic activity of the composite catalysts
      under ultraviolet light irradiation. The effects of doped content, activation
      temperature, time, initial concentration of methanol and gas flow rate on the
      catalytic activity were investigated. The results showed that after doping a
      certain amount of CeO2 and ZrO2, crystallization process of TiO2 was restrained,
      particles of catalysts are smaller and more uniform. Doping ZrO2 not only
      significantly improved the catalytic activity, but also increased thermal
      stability. Doping H3PW12O40 also enhanced the catalytic activity. The catalytic
      activities of binary and ternary composite photocatalysts were significantly
      higher than un-doped TiO2. The dynamics law of photocatalytic reaction over the
      binary CeO2/TiO2 and ZrO2/TiO2 catalysts has been studied. The activation energy
      15.627 and 15.631 kJ/mol and pre-exponential factors 0.5176 and 0.9899 s(-1) over
      each corresponding catalyst were obtained. This reaction accords to the first
      order dynamics law.

PMID- 19862970
TI  - Method for rapid on-site identification of VOCs.
AB  - Rapid on-site identification of volatile organic compounds (VOCs) in ambient air
      is an important first step in remediation efforts. This study describes
      modification of a commercially available, portable GC/MS system and development
      of an analysis protocol for rapid (< 3 min) sampling and identification of VOCs
      typically found at contaminated sites at the low ppbv level.

PMID- 19862971
TI  - Removal of heavy metals from artificial metals contaminated water samples based
      on micelle-templated silica modified with pyoverdin I.
AB  - The micelle-templated silica (MTS) was firstly chemically modified with 3
      glycidoxypropyl-trimethoxysilane (GPTMS) before immobilized with pyoverdin I. The
      characteristics of pyoverdin I-anchored onto the modified MTS were investigated
      using fluorescence, infrared spectra and scanning electron microscopy. The
      specific surface area of all materials was calculated by Brunauer, Emmett and
      Teller (BET) method using nitrogen isotherm adsorption data. As the results, the
      surface area of commercial silica gel decreased from 609.2 to 405.4 m2/g, it
      indicated that the pyoverdin I could be immobilized onto the surface of silica
      solid support. This adsorbent was used for extraction of Fe(III), Cu(II), Zn(II),
      and Pb(II) in artificial metals contaminated water. Experimental conditions for
      effective adsorption of trace levels of metal ions were optimized with respect to
      different experimental parameters using batch procedure. The optimum pH value for
      the removal of metal ions simultaneously on this adsorbent was 4.0. Complete
      desorption of the adsorbed metal ions from the adsorbent was carried out using
      0.25 mol/L of EDTA. The effect of different cations and anions on the adsorption
      of these metals on adsorbent was studied and the results showed that the proposed
      adsorbent could be applied to the highly saline samples and the sample which
      contains some transition metals.

PMID- 19862972
TI  - [Bright prospects of antibody-based drug for targeted cancer therapy].

PMID- 19862973
TI  - [Interventional therapy of intracranial vascular stenosis].

PMID- 19862974
TI  - [Hospital discharge criteria for definitely diagnosed H1N1 type A influenza
      patients (interim)].

PMID- 19862975
TI  - [Inhibitory effect of lidamycin upon vasculogenic mimicry and its induction of
      apoptosis in glioma cells].
AB  - OBJECTIVE: To evaluate the in vitro effects of lidamycin upon vasculogenic
      mimicry and apoptosis induction in glioma cells. METHODS: Tube formation assay
      was performed to estimate the inhibitory effects of lidamycin upon vasculogenic
      mimicry in C6 and U87 glioma cells. The vasculogenic mimicry of glioma cells was
      photographed and enumerated. Annexin V-FITC/PI was used for determination of
      glioma cell apoptosis with flow cytometry. RESULTS: Vasculogenic mimicry assay
      indicated that 0.1 nmol/L, 0.5 nmol/L and 1 nmol/L lidamycin showed significant
      inhibition of vasculogenic mimicry in C6 and U87 cells. Comparing with C6 control
      group (14.7 +/- 1.2), 0.1 nmol/L (12.7 +/- 0.6), 0.5 nmol/L (9.0 +/- 1.7) and 1
      nmol/L (4.7 +/-0.6) lidamycin inhibited vasculogenic mimicry in C6 cells with
      statistical significances (P = 0.013, P = 0.005 and P = 0.0002 respectively).
      Comparing with U87 control group (14.7 +/- 1.2), the vasculogenic mimicry of 0.1
      nmol/L (10.0 +/- 2.0), 0.5 nmol/L (8.3 +/- 1.5) and 1 nmol/L lidamycin (4.3 +/-
      0.6) treated U87 cells showed statistical significances (P = 0.025, P = 0.00 and
      P = 0.0009 respectively). The apoptotic ratios of same dosa ges lidamycin treated
      C6 cells and U87cells showed a similar tendency as vasculogenic mimicry
      inhibition (P < 0.001). Lidamycin was more potent than neocarzinostatin in
      vasculogenic mimicry inhibition and apoptosis induction of C6 cells and U87
      cells. Conclusion Lidamycin can inhibit vasculogenic mimicry and promote
      apoptosis of glioma cells. Thus it is a promising drug in glioma treatment.
      Further researches on the therapeutic efficacy of enediyne antibiotics in glioma
      are needed.

PMID- 19862976
TI  - [The relationship between multi-drug resistance and proportion of leukemia stem
      cells and expression of drug transporters in drug-resistant leukemia K562/ADM
      cells].
AB  - OBJECTIVE: To investigate the drug resistance, proportion of leukemia stem cells
      (LSC) and expression of P-glycoprotein (P-gp) and breast cancer resistance
      protein (BCRP) in drug-sensitive and multidrug-resistant leukemia cell
      population. METHODS: The multidrug-resistant leukemia K562/ADM cell and its
      parental K562 cell were used as the model cells. The drug sensitivity was tested
      with a MTT assay. Flow cytometry was employed to detect the immunophenotype of
      stem cells and the expression of P-gp and BCRP. The self-renewal and
      proliferating potential were examined with methylcellulose colony-forming unit
      assay. RESULTS: K562/ADM cells were highly resistant to adriamycin, daunorubicin
      and etoposide. The amount of CD34+, CD123+ and CD34+ CD38- cells in K562/ADM
      cells was much higher than that in K562 cells, and the proportion of CD34+ CD38-
      CD123+ cells (LSC) in K562/ADM cells was (5.23 +/- 0.21)% versus (1.27 + 0.17)%
      in K562 cells, which was 4.12-fold higher than that in K562 cells. Both P-gp and
      BCRP were overexpressed in K562/ADM cells relative to K562 cells, and the
      K562/ADM cells coexpressing P-gp and BCRP were 11.25-fold higher over K562 cells.
      The proportion of CD34+ CD38- CD123+ BCRP+ and CD34+ CD38- P-gp+ BCRP+ cells in
      K562/ADM cells were (4.13 +/- 0.40)% and (5.80 +/- 1.19)% respectively, which
      were 3.66- and 11.37-fold higher than the same cells in K562 cells [(1.13 +/-
      0.15)% and (0.51 +/- 0.01)%]. Furthermore, drug-resistant K562/ADM cells
      displayed 4.17-time greater colony-forming ability over the parent K562 cells,
      corresponding to the proportion of LSCs in K562/ADM cells. CONCLUSIONS: The ABC
      transporters-overexpressing LSC population exists in drug-resistant leukemic
      K562/ADM cells relative to drug-sensitive K562 cells, and the drug-resistant LSCs
      may be the source of chemotherapeutic resistance of leukemia.

PMID- 19862977
TI  - [Screening the differential expression of adriamycin-resistance related genes of
      breast cancer by cDNA microarray].
AB  - OBJECTIVE: To study the differential gene expression of adriamycin-resistance of
      breast cancer cell line MCF-7/ADR as compared with its parent cell MCF-7 and
      screen the related genes. METHODS: The in vitro inhibitory rate of MCF-7/ADR and
      MCF-7 cell lines to ADM (adriamycin) was examined by MIT assay. Then a cDNA
      microarray representing 14,755 genes was used to analyze the expression profiles
      of these two breast cancer cell lines. RESULTS: The inhibitory rate of MCF-7/ ADR
      to ADM was lower than that of MCF-7(P <0.05)and the drug resistance to ADR of MCF
      7/ADR was stronger than that of MCF-7. There were 2374 differential expression
      genes in MCF-7/adr and MCF-7 cell lines, of which 1099 genes upregulated with 99
      genes 10-fold upregulated and 1275 genes downregulated with 71 genes 10-fold
      downregulated. The important upregulated genes were Bcl-2, GSTP1, c-myc, MMP-1
      and NNMT while those downregulated ones p53, p21, p27 and CYPIA1. CONCLUSION:
      Drug resistance of breast cancer is a complicated process involving the
      expression of many upregulated or downregulated genes. The application of gene
      chip in screening drug-resistant genes may be a new approach for selecting the
      optimal chemotherapeutic regimens. [Key words]

PMID- 19862978
TI  - [Prevalence of and risk factors associated with diabetic retinopathy in pre
      diabetic and diabetic population in Shanghai community].
AB  - OBJECTIVE: To determine the prevalence and risk factors of diabetic retinopathy
      (DR) in the Diabetes Mellitus (DM) and impaired glucose regulation (IGR)
      population in Shanghai Community. METHODS: DR screening after the epidemiologic
      study of metabolic syndrome in Huayang and Caoyang Community, Shanghai was
      conducted among 1300 patients with DM or IGR during June 2005 and March 2006,
      Digital non-mydriatic fundus photography was performed for each eye in all
      subjects. Other factors, including diabetes related history, BMI, WHR, fasting
      plasma glucose, HbA1c, serum lipid and blood pressure were also assessed. 642
      patients, 312 males and 330 females, aged 65 +/- 13, with complete data were
      enrolled into the analysis. RESULTS: The prevalence of DR was 19.9% in the
      diabetic population, and the prevalence of mild, moderate, severe non
      proliferative retinopathy and proliferative retinopathy was 12.0%, 5.1%, 2.3% and
      0.5%, respectively; the prevalence of DR in IGR reached 8.0%. Logistic regression
      analysis revealed that HbA1c level and diabetes duration were both independently
      associated with diabetic retinopathy. CONCLUSION: The prevalence of DR was high
      in both DM and IGR population. Bad blood glucose control and long diabetes
      duration both increased occurrence of DR.

PMID- 19862979
TI  - [Mutation analysis and prenatal diagnosis of sporadic DMD/BMD families].
AB  - OBJECTIVE: To analyze the pathogenic mutation of sporadic patients in Duchenne/
      Becker muscular dystrophy (DMD/BMD) families and to perform prenatal diagnosis,
      identify the female carriers and evaluate the ratio of de novo mutation in these
      pedigrees. METHODS: A total of 30 sporadic DMD/BMD families were included.
      Traditional multiplex PCR was used to detect the 18 exons in the deletion hot
      area of DMD gene. MLPA was used to detect the deletion or duplication mutations
      of DMD gene for 30 patients and 28 females from 23 families. Prenatal diagnosis
      was performed in 19 families. RESULTS: Deletion mutation was detected in 19
      patients through mPCR. Twenty-one deletions and 3 duplication mutations were
      detected by MLPA. Among 21 mothers, 10 mothers were carriers of deletion mutation
      and two duplication mutation carriers. The other 9 mothers were non-carriers, the
      mutations in these families were de novo and the ratio was 37.5%. Among seven
      sisters, five were carriers and two non-carriers. In the prenatal diagnosis
      families, 2 of 8 female fetuses were carriers and 5 of 12 male fetus patients.
      CONCLUSION: The MLPA technique has proved to be an accurate and reliable tool not
      only for the deletion and duplication mutations of DMD patients, but also for the
      prenatal diagnosis and the female carriers in these families. Prenatal diagnosis;

PMID- 19862980
TI  - [Comparative study on clinical and pathological changes of liver fibrosis with
      diffusion-weighted imaging].
AB  - OBJECTIVE: To evaluate the clinical practical value of apparent diffusion
      coefficient (ADC) measurements based on diffusion-weighted MR imaging (DWI) for
      quantification of liver fibrosis and inflammation for hepatitis viral infection.
      METHODS: Diffusion-weighted MRI with parallel imaging was prospectively performed
      on 85 patients with chronic hepatitis and on 22 healthy volunteers within a
      single breath-hold using a single-shot spin-echo echo-planar sequence at b values
      of 100, 300, 500, 800 and 1000 s/mm2 respectively. ADC values of liver were
      measured with five different b values. The inflammation grades and fibrosis
      stages were evaluated histologically by biopsy. One-way analysis of variance and
      Spearman' s rank correlation test were used for statistical analysis. Receiver
      operating characteristics analysis was used to assess the performance of ADC in
      predicting the presence of stage > or = 2 and stage > or = 3 hepatic fibrosis,
      and grade > or = 1 hepatic inflammation. RESULTS: There was moderate negative
      correlation between hepatic ADC values and fibrosis stage. And the best
      correlation was obtained for a b value of 800 s/mm2 (r = -0.697, P = 0. 000). At
      all b values there was a significant decrease in hepatic ADC in patients with
      stage < or = 1 versus stage > or = 2 fibrosis and stage < or = 2 versus stage >
      or = 3 fibrosis (P < 0.05). Hepatic ADC was a significant predictor of stage > or
      = 2 and > or = 3 fibrosis. The areas under the curve were 0.909 vs 0.917,
      sensitivity 76.6% vs 80.0% and specificity 88.3% vs 91.5% (ADC with a b value of
      800 s/mm2, 1.26 x 10(-3) mm2/s or less and 1.19 x 10(-3) mm2/s or less). There
      was weak to moderate negative correlation between ADCs and inflammation grade.
      Hepatic ADC was a significant predictor of grade > 1 inflammation with an area
      under the curve of 0.781, sensitivity of 60.0% and specificity of 86.4% (ADC with
      a b value of 500 s/mm2, 1.54 x 10(-3) mm2/s or less). CONCLUSION: The DWI
      measurement of hepatic ADC can be used to quantify liver fibrosis and
      inflammation. It will be a new approach for early diagnosis and therapeutic
      follow-up of hepatic fibrosis.

PMID- 19862981
TI  - [The study of Chinese optimal anticoagulant range of warfarin for venous
      thromboembolism].
AB  - OBJECTIVE: The aim of trial is to observe the Chinese bleeding frequency and
      frequency of recurrent VTE in different international normalized ratio (INR)
      range of warfarin for venous thromboembolism (VTE) including deep venous
      thrombosis (DVT) and pulmonary embolism (PE), and to search optimal INR range.
      METHODS: We conducted a randomized, double-blind cohort trial, in which 180
      patients were assigned to apply warfarin in a target INR of 1.50 to 1.99 (group
      A), a target INR of 2.00 to 2.50 (group B) or a target of INR of 2.51 to 3.00
      (group C). Every group had respectively 60 patients. After they had completed
      warfarin therapy to be stability kept with those target INR range for two or more
      weeks, this study would be begun to observe the bleeding frequency and frequency
      of recurrent VTE. RESULTS: There was significant difference in recurrent VTE
      frequency between Group A (8.3%) and BC (1.7%, P = 0.042). The minor bleeding
      frequency of Group A, B and C is respectively 8.3%, 18.3% and 6.7% (P = 0.089).
      The moderate bleeding frequency of Group A and BC is respectively 3.3% and 7.5%
      (P = 0.341), and large bleeding frequency of them is respectively 0% and 3.3% (P
      = 0.303). To patients whose age above 62 year, major bleeding episode occurred
      respectively in 1 patient assigned to INR of 1.5-2.5 and in three patients
      assigned to Group C (hazard ratio, 12. 600; 95 percent confidence interval, 1.183
      134.238). CONCLUSION: Warfarin therapy in INR of 2.0-3.0 is more effective than
      INR of 1.5-1.99 for the long-term prevention of recurrent VTE. And warfarin
      regimen in INR of 2.0-3.0 does not increase the risk of major bleeding either. So
      to general Chinese, INR ought to be recommended in 2.0-3.0. To patients whose age
      above 62 year, INR ought to be recommended between 2.0 to 2.5.

PMID- 19862982
TI  - [Postoperative acute renal failure in adult patients with cardiac surgery:
      evaluation of the RIFLE classification].
AB  - OBJECTIVE: To evaluate the ability of the RIFLE classification to predict
      hospital mortality in adult patients who underwent cardiac surgery. METHODS: From
      October 1st 2006 to December 31st 2006, five hundred and nine adult patients who
      underwent coronary artery bypass grafting and/or valve operation were enrolled in
      this study. Renal function was assessed daily according to the RIFLE
      classification, meanwhile, APACHE II score and SOFA score were also evaluated, as
      well as the maximum scores were recorded. RESULTS: Mean duration of ventilation
      support was 18 (14-19) hours, the time of ICU stay was 1.4 +/- 1.0 days, and the
      time of postoperative hospital stay was 12.0 (10.0-15.0) days. 167 patients
      (32.8%) incurred postoperative ARF according to the RIFLE classification. The
      overall mortality was 4.3% (22/502). A significant increase (P < 0.01) was
      observed for mortality based on RIFLE classification. By applying the area under
      the receiver operating characteristic curve, the RIFLE classification had more
      powerful discrimination power [0.933, (95% CI 0.872-0.995), P < 0.001].
      CONCLUSIONS: ARF is one of the major complications in postcardiotomy patients.
      Analytical data suggested the good discriminative power of the RIFLE
      classification for predicting inpatient mortality of adult postoperative patient
      with ARF, and the RIFLE classification is simple and practically performed.
      According to the RIFLE classification, patients with RIFLE class I or class F
      incur a significantly increased risk of in-hospital mortality compared with those
      who never develop ARF.

PMID- 19862983
TI  - [Postoperative survival comparison of non-small cell lung cancer between disease
      with peripheral direct adjacent invasion and resectable T4 disease with
      mediastinal structures invasion].
AB  - OBJECTIVE: To determine the postoperative survival of non-small cell lung cancer
      with peripheral adjacent lobe invasion by comparing it with that of resectable T4
      disease with mediastinal structures invasion, and hence try to find out some clue
      concerning how to define these patients for a reasonable T stage. METHODS: A
      retrospective analysis was conducted to assess the survival of NSCLC patients
      with peripheral direct adjacent lobe invasion (group A, n = 28), and compared it
      with that of with mediastinal structures invasion (group B, n = 21). All patients
      underwent surgery between March, 1997 and October, 2006, and were pathologically
      confirmed with NOMO disease. Kaplan-Meier method was used to calculate the
      survival, and Log-Rank test was used to compare the postoperative survival
      between two groups. RESULTS: The sex, age, pathology, and pulmonary function were
      well balanced between the two groups. There was one operative death from group A.
      The disease specific 2 year, 3year, 5 year survival in group A and group B was:
      68.7%, 61.1%, 40.7%, and 64.7%, 58.2%, 43.7%, respectively. The median survival
      for group A and group B was 54 months and 49 moths, respectively, with no
      statistically significant difference (P = 0.931). CONCLUSIONS: NSCLC with
      peripheral adjacent lobe invasion has a similar survival prognosis with that of
      resectable T4 disease with mediastinal structures invasion. Among carefully
      selected patients, long-term survival is anticipated for NSCLC with adjacent lobe
      invasion. However, further studies are needed to determine the optimal T stage
      for these patients.

PMID- 19862984
TI  - [Etiology, diagnosis and treatment analysis of 37 cases with orbital fistula].
AB  - OBJECTIVE: To present some instruction in diagnosis and treatment of the orbital
      fistula by analyze the clinical manifestation. METHOD: The clinical data for 37
      cases with orbital fistula treated during 1980 to 2007 were analyzed
      retrospectively. RESULTS: Among 37 cases with orbital fistula, there are 21 cases
      caused by foreign bodies, including 17 cases by retained wooden bodies, 3 cases
      by iatrogenic foreign bodies and 1 case by firecrackers. There are 9 cases caused
      by orbital cysts, including 5 cases dermoid cysts, 3 cases epidermoid cysts and 1
      case frontal mucopyocele. There are 6 cases orbital infection inflammation,
      including 5 cases osteomyelitis and 1 case orbital abscess. There is 1 case
      eosinophilic granuloma. Different etiologies have characteristic features.
      Medical history, fistula examinations and imaging examinations must be analyzed
      synthetically in order to make proper etiological diagnosis. Eradicate etiologies
      and resect fistula are most important. It is necessary to make an ancillary
      therapy, such as ENT treatment. CONCLUSIONS: The common etiologies of orbital
      fistula are retained foreign body, dermoid cysts and osteomyelitis. The
      pathogenesis include infective inflammation, congenital heteroplasia, operation
      and tumor. B-scan ultrasonography, CT, and MRI can be used for the localization
      and qualitation diagnosis. There are comprehensive approaches for diagnosis and
      management of this type of injury. In order to give an effective therapy, we must
      make an accurate diagnosis and analyze the features of fistula.

PMID- 19862985
TI  - [Posterior fusion versus posterior interbody fusion in segmental spinal fixation
      for aged spondylolisthesis].
AB  - OBJECTIVE: Clinical and radiographic results in 30 consecutive patients
      undergoing posterior lumbar fixation and posterior facet joint or posterior
      interbody fusion for Meyerding Grade II/III spondylolisthesis were assessed: (1)
      to address the suitability of a dynamic stabilization; and (2) to investigate
      whether there are differences in terms of clinical and functional results between
      these two types of arthrodesis. METHODS: Fourteen patients underwent posterior
      interface fusion (PLF) and implantation of TSRH-3D system. Posterior lumbar
      interbody fusion (PLIF) and placement of the same system were performed in 16
      patients. Clinical, economic, functional and radiographic data were recorded both
      pre- and postoperatively. RESULTS: The average changes in Prolo Scale of economic
      and functional scores were 1.25 and 1.64 respectively, in patients undergoing
      posterior fusion; the average measured vertebral slippage was 48.6% (range 32%
      65%) preoperatively and 17.5% (range 15%-25%) postoperatively. In patients
      undergoing PLIF, the average changes in economic and functional score were 1.18
      and 1.39 respectively, and the average preoperative vertebral slippage was 44.2%
      (range 30%-55%) versus 20.3% (range 18%-26%) postoperatively. CONCLUSION: The use
      of a segmental pedicle screw fixation with TSRH-3D was able to successfully
      combine the goal of solid fusion with the requirements of nerve root
      decompression. When these two fusion techniques were compared, PLIF was superior
      to PLF because of an overall superior reliability and system resistance. But
      their clinical outcomes did not differ greatly (P > 0.05).

PMID- 19862986
TI  - [Effects of VCAM-1 siRNA on restenosis following carotid endarterectomy:
      experiment with rats].
AB  - OBJECTIVE: To evaluate the inhibitory effects of VCAM-1 siRNA on VCAM-1 protein
      expression and restenosis following carotid endarterectomy in rats. METHODS:
      Lentivirus-based VCAM-1 siRNA was constructed and its efficacy of blocking VCAM-1
      protein expression in endothelial cells and carotids was identified by Western
      blot. Doppler ultrasonography and morphometric analysis were performed to measure
      the degree of restenosis. RESULTS: VCAM-1 siRNA decreased the protein expression
      of VCAM-1 in cultured endothelial cells and carotids. Treatment of VCAM-1 siRNA
      showed a significant reduction in the restenosis and manifested as an increased
      blood velocity and linear diameter as compared with control siRNA (P < 0.05).
      Morphometric analysis showed that the ratio of intima to media area (I/M)
      increased significantly in CEA group (3.99 +/- 0.65) versus sham-operated group
      (0.35 +/- 0.13) (P < 0.05). Furthermore, VCAM-1 siRNA resulted in an evident
      decrease in the neointimal area (1.79 +/- 0.43) as compared with that of the
      control siRNA (4.33 +/- 0.59) (P < 0.05). CONCLUSION: VCAM-1 plays an important
      role in pathogenesis of restenosis after carotid endarterectomy. VCAM-1 siRNA
      blocks VCAM-1 protein expression and alleviates the restenosis following carotid
      endarterectomy in rats.

PMID- 19862987
TI  - [Effects of lipid emulsion on hemodynamics and pharmacokinetics of mongrel dogs
      with bupivacaine-induced cardiac depression].
AB  - OBJECTIVE: To investigate the effects of Intralipid injection on hemodynamics and
      pharmacodynamics of mongrel dogs with bupivacaine-induced cardiac depression.
      METHODS: Fourteen dogs were randomly divided into Intralipid injection group (the
      experiment group) and normal saline group (the control group). 0.5% bupivacaine
      was administrated at a constant rate until the mean arterial pressure (MAP)
      decreased to 60% of the basic value. Intralipid injection was administered in the
      experiment group. The hemodynamic parameters were recorded and blood samples were
      taken from femoral artery at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 min
      after stopping bupivacaine infusion for determination of plasma concentration by
      HPLC. The pharmacokinetic parameters were calculated by Drug and Statistics soft
      version 2.0. RESULTS: After the treatment of Intralipid injection, MAP, CO, HR
      increased significantly, compared to those of the control group (P < 0.05). The
      AUC(o-t) was (192 +/- 34)mg x L(-1) x min(-1) versus (271 +/- 81) mg x L(-1) x
      min(-1) and the AUC(0-infinity) was (231 +/- 62) mg x L(-1) x min(-1) versus (368
      +/- 140) mg x L(-1) x min(-1) in the experiment group and the control group
      respectively. Vz (4.5 +/- 1.1 L/kg versus 3.3 +/- 0.9 L/kg) of bupivacaine in the
      experiment group was significantly higher than that in the control group (P <
      0.05). CONCLUSION: Intravenous infusion of Intralipid have beneficial effects on
      the hemodynamics of mongrel dogs with bupivacaine-induced cardiac depression. One
      of the mechanism of the beneficial effects was probably that Intralipid injection
      increases the apparent volume of bupivacaine distribution and that decreases
      blood concentration. [Key words]

PMID- 19862988
TI  - [Expression of M4 receptor in normal guinea pigs retina].
AB  - OBJECTIVE: To detect the expression and distribution of M4 receptor in normal
      guinea pigs retina. METHODS: Twenty one normal 4-week-old triad color guinea were
      selected. Eyes were enucleated. Seven eyes were fixed, paraffin-embedded and cut
      into sections. Expression and distribution of M4 receptor were detected using
      immunohisto chemically. The rest eyes were dissected. Tissue of retina were
      separated. RNA and protein of different tissue were extracted respectively. M4
      receptor at mRNA level and protein level were detected by RT-PCR and Western blot
      methods. RESULTS: receptor at mRNA level was detected in normal guinea retina,
      with the amplification product at 221 bp. No product was detected in negative
      control. M4 receptor at protein level was detected in normal guinea retina, with
      signal band at 38,000. No signal was detect in negative control. As detected by
      immunohistochemistry, M4 receptor was detected in RPE cells, photoreceptor layer,
      outer nuclear layer, inner nuclear layer, most ganglion cells and the junctional
      zone of inner plexiform layer and inner nuclear layer. CONCLUSION: M4 receptor
      was expressed in normal guinea retina.

PMID- 19862989
TI  - Protecting vulnerable adults.

PMID- 19862990
TI  - Lessons in care of the vulnerable.

PMID- 19862991
TI  - Minor injury units.

PMID- 19862992
TI  - Relocation of an emergency service.
AB  - Moving to new facilities is common in today's health service because of mergers,
      the restructuring of units and improvements in service delivery. Central to the
      success of such relocation projects is the involvement of clinical teams. This
      article describes the various stages of a successful relocation of an emergency
      unit in London, and its co-location with a newly created polyclinic. It also
      describes the experiences of one of the members of the clinical team.

PMID- 19862993
TI  - Nurse cannulation: introducing an advanced clinical skill.
AB  - Many patients admitted to emergency departments (EDs) require therapy delivered
      by cannula. Mid-Western Regional Hospital, Tipperary, used to run a system in
      which many patients had to endure two invasive procedures: on arrival their blood
      was taken by nurses and later they were cannulated by doctors. To reduce the
      number of procedures, ED nurses initiated a project to extend their skills to
      include cannulation. The new system of nurse cannulation at triage has also
      helped reduce waiting times.

PMID- 19862994
TI  - Casting: U-slabs.
AB  - This article continues a short series of articles on how to apply casts. It
      examines how U-slabs should be applied following fracture of the shaft of the
      humerus.

PMID- 19862995
TI  - X-ray interpretation by emergency nurse practitioners.
AB  - An audit of the ability of emergency nurse practitioners to interpret X-rays
      accurately has found that they can practise well within nationally acceptable
      limits for producing false positive and false negative results.

PMID- 19862996
TI  - Non-invasive ventilation: a nurse-led service.
AB  - Respiratory diseases are the third most common presentations to emergency
      departments (EDs) in the Republic of Ireland. Evidence suggests that early non
      invasive ventilation (NIV) is often the treatment of choice, particularly for
      patients with chronic obstructive pulmonary disease. Therefore, having access to
      NIV in EDs is likely to improve patient outcomes and reduce the likelihood of
      their mechanical ventilation.

PMID- 19862997
TI  - Better in the long run.
AB  - Outside of her work in an emergency department, Hazel Mortimer develops clinical
      care and operational management skills as a St John Ambulance volunteer,
      attending some of the biggest sporting and social events in the UK. She plans to
      be at the 2010 London marathon, when she expects to keep going long after the
      last runner crosses the finishing line

PMID- 19862998
TI  - ANA responds to concerns about healthcare reform and nursing.

PMID- 19862999
TI  - Pathways to Nursing: an innovative program to encourage high school students to
      enter nursing.
AB  - Pathways to Nursing was implemented as a partnership between Northern Kentucky
      University School of Nursing and Health Professions, a local high school in the
      Northern Kentucky region, a local hospital system, and a large regional medical
      practice. The goal of this project was to increase interest in nursing as a
      career among local high school students in order to impact the nursing shortage
      and improve the health of Northern Kentuckians. Pathways to Nursing activities
      allowed high school students to explore post-secondary nursing education by
      participating in nursing career day activities at the university and summer
      nursing camp which included an overnight stay at the university and nurse
      shadowing days at the local hospital. High school students were exposed to
      various clinical experiences, diverse nursing roles, nursing skills laboratory
      activities and human simulation activities. Students also met with nursing
      faculty, academic advisors, and university admissions counselors. One hundred and
      twenty-four high school students participated in Nurse Career Days over the two
      year period of the program, and 45 students participated in Summer Nurse Camp
      over two summers. Ninety-four percent of the high school students who
      participated in Nurse Career Day stated they would "probably choose" or
      "definitely choose" the university to attend nursing school; 93.6% stated they
      "might want to be a nurse" or "definitely would want to be a nurse", and 93.7%
      rated the information covered as very relevant. Sixty-two percent of the students
      reported that they "definitely want to be a nurse" after attendance at Summer
      Nurse Camp. The goal of the Pathways to Nursing program was to provide Northern
      Kentucky high school students the opportunity to explore nursing through active
      learning experiences that augment career and academic interests. Collaborative
      relationships were developed between the University, the School of Nursing and
      Health Professions (SNHP), a local hospital system and a regional medical
      practice to encourage Northern Kentucky high school students to pursue a career
      in nursing. The following objectives were used to complete this project. 1. Build
      collaborative relationships among all partners to plan, implement and evaluate
      all phases of the Pathways to Nursing program. 2. Complete Pathways to Nursing
      activities throughout the year that allow high school students to explore post
      secondary nursing education and diverse clinical experiences. 3. Implement
      cooperative learning experiences for "Pathways to Nursing" high school students
      through educational and mentoring activities conducted by university
      undergraduate and graduate nursing students.

PMID- 19863000
TI  - Education is the key to the prevention of lawnmower accidents.

PMID- 19863001
TI  - Kosair Children's Hospital brings NICU babies and families together.

PMID- 19863002
TI  - [Investigation about the use of analgesics for the reduction of castration
      induced pain in suckling piglets].
AB  - The pre-emptive use of analgesics for the reduction of pain induced by the
      castration of suckling piglets was investigated by measuring cortisol before as
      well as 30 min (minutes), 1 h (hour), 4 h and 24 h after castration/handling and
      by post surgical behaviour (0-60 min and 180-240 min after castration/handling).
      245 male, 4 to 6 days old piglets with a good general condition were divided into
      twelve groups. The drugs meloxicam, flunixin, metamizole or carprofen,
      respectively, or saline solution in control piglets were administered 15 to 30
      min before manipulation. All tested non-opioid analgesics reduced the rise of the
      cortisol concentration after castration. Piglets receiving meloxicam and flunixin
      had significantly lower values 30 min, 1 h and 4 h after castration than the
      control group, and already after 1 h they did not differ significantly from the
      corresponding handling groups. The frequency of occurrence of tail wagging,
      drooping the tail and changing the position was explicitly reduced when meloxicam
      and flunixin were injected before castration. The effect of flunixin was most
      clear. Results indicate that non-opioid analgesics, especially efficient anti
      inflammatory drugs like meloxicam and flunixin, are capable of reducing
      castration-induced pain in piglets.

PMID- 19863003
TI  - [Different CO2-stunning procedures and post mortem obtained lung lesions in
      response to the corneal reflex and parameters in blood of slaughtered pigs].
AB  - The effect of different CO2-stunning on the corneal reflex response and blood
      parameters in (arterio-venous) killing blood was investigated in n = 614
      slaughter pigs (carcass weight = 92-94 kg) at two different abattoirs. CO2
      anaesthesia lead to remarkable decrease of PO2 (hypoxaemia), increase of PCO2
      (hypercapnia), decrease of pH (respiratory acidosis) and increase of [strong ion
      difference = SID3] (basic reaction caused by electrolytes). Pigs with subclinical
      post mortem obtained lung lesions showed no significant modified value of the
      reflex answer or changes in parameters of killing blood compared to the animals
      with healthy lungs. The CO2-stunning with 90% CO2 and 120 s exposure time
      resulted in notably less undesired positive reflex responses (6% of slaughter
      pigs) than the CO2-stunning with 90% CO2 and only 90 s exposure time (15% of
      slaughter pigs). The occurence of the positive reflex response, which means an
      inadequate depth of anaesthesia, in slaughter pigs can be safely eliminated by
      use of qualified cut off values of killing blood parameters. These parameters can
      be measured rapidly and validly with ion-sensitive electrodes, making a
      beneficial monitoring of the used CO2-stunning possible.

PMID- 19863004
TI  - Detection of beta2 and major toxin genes by PCR in Clostridium perfringens field
      isolates of domestic animals suffering from enteritis or enterotoxaemia.
AB  - The production of Clostridium (C.) perfringens toxins in the intestine is an
      important cause of enteritis and enterotoxaemia in livestock. In the present
      study, the alpha toxin and the genes encoding beta2 and epsilon toxin could be
      frequently detected by means of phenotypical and PCR examinations in these
      bacteria. The C. perfringens isolates originated from 1213 field samples taken
      from diseased or perished livestock located in the north-eastern administrative
      districts of Baden-Wurttemberg (Germany) from 2005 to 2008. The beta2 toxin gene
      of C perfringens was detected in all animal species examined, comprising pigs,
      the small ruminants sheep and goats, cattle, horses, rabbits, alpacas and lamas,
      and fallow deer. Among all the animal species included in this study, pigs
      attracted attention by a high quota of 74.2% (610 of 822) cpb2-positive C.
      perfringens isolates in comparison to the other animal species tested, revealing
      a quota of 20.8% (72 of 346). Beta2 toxigenic isolates could be predominantly
      cultivated from the faeces of young piglets. The beta toxin gene was detected in
      isolates from piglets and small ruminants only, amounting to 82.5% (33 of 40) in
      piglets in combination with the cpb2 gene. In this context, cpb2/cpb-positive C.
      perfringens isolates of piglets could be clearly detected more often in the
      intestine of perished animals (18 of 158) than in faeces (15 of 629).
      Furthermore, cpb2-bearing C. perfringens isolates were detected in cattle,
      horses, rabbits, alpacas and lamas, and fallow deer to a notable degree. The
      detection of C. perfringens isolates carrying the epsilon toxin gene was
      restricted to sheep and goats. Of a total of 242 small ruminants that succumbed
      to sudden death, 71 (29.3%) harboured epsilon toxin-positive C. perfringens
      isolates in their intestines. These cases clustered seasonally in the second
      quarter (April, May, and June) of the year. Neither the isolates bearing the
      beta2 nor beta toxin gene nor those carrying the epsilon toxin gene showed an
      annualised accumulation within the sample period. The iota toxin obviously plays
      a minor role, for in only one case could the encoding toxin gene be detected in
      an isolate from the intestine of a perished lamb. The need for effective
      vaccination is discussed, particularly with regard to the beta2 and epsilon
      toxin. To combat diseases caused by toxin-producing C. perfringens isolates
      successfully, the implementation of consistent vaccination regimens in
      combination with controlled feeding is recommended.

PMID- 19863005
TI  - The tissue compatibility of different Mycoplasma hyopneumoniae vaccines is mainly
      dependent upon their adjuvants.
AB  - Aim of this study was to investigate the tissue compatibility of three
      differently adjuvated Mycoplasma hyopneumoniae vaccines. Local tissue reactions
      after an intramuscular injection of 2 ml doses of Stellamune Mycoplasma (oil
      adjuvated; Pfizer, Karlsruhe, Germany) and Suvaxyn M.hyo (carbopol-adjuvated;
      Fort Dodge, Wurselen, Germany) were examined in suckling and weaned piglets.The
      different effects of the injection volumes of 1 ml and 2 ml of the vaccine M+PAC
      (aluminium hydroxide- and oil-adjuvated; essex tierarznei, Munich, Germany) on
      the tissue compatibility were assessed in weaned piglets. All animals were
      euthanized 6 days post vaccination. Clinical investigation of the injection sites
      revealed a slight to moderate increase in tissue consistency, a mild increase of
      local skin temperature, as well as a mild reddening of the skin in both age
      groups four hours after the application of all vaccines. Concerning gross
      pathological and histological changes, most prominent changes were noted
      following vaccination with the M+PAC vaccine. However, the other two vaccines
      also induced mostly mild pathoanatomical changes at the injection sites.
      Histologically, Stellamune Mycoplasma caused a slight degeneration of muscle
      fibres and invasion of macrophages, whereas Suvaxyn M.hyo additionally led to a
      moderate necrosis and the appearance of giant cells. The dual-action-adjuvated
      vaccine M+PAC induced severe necrotic lesions and vacuoles. In addition, the
      degree of tissue reaction appeared to be related to the size of the administered
      volume. In general, the age of the animals seemed to be of minor importance
      concerning the quality of the tissue reactions.

PMID- 19863006
TI  - Compatibility of a combined vaccination against Haemophilus parasuis and porcine
      reproductive and respiratory syndrome virus.
AB  - Objective of this study was to assess the tissue compatibility of a vaccination,
      combining vaccines against Haemophilus parasuis and Porcine Reproductive and
      Respiratory Syndrome Virus (PRRSV). Clinical examinations were done with special
      respect to local tissue reactions after injection of 2 ml each of either Porcilis
      Glasser, or Porcilis PRRS (both Intervet, Unterschleissheim, Germany), or a
      mixture of the two vaccines. Animals were euthanized on day six post vaccination.
      Clinical as well as gross pathological or histological alterations at the
      injection sites were similar in all groups and were predominantly low grade.
      Clinical investigation of the injection sites revealed a mild increase in tissue
      consistency as well as mild swelling and reddening after the application of
      Porcilis PRRS and the mixture of the two vaccines. In the Porcilis Glasser group,
      few cases of moderately increased skin consistency and mild swelling were noted 4
      hours post injection. Pathological examination showed mild haemorrhages and mild
      pallor of the tissue with a maximum linear width of 2 cm at the injection site in
      most animals. Histological examination predominantly revealed a mild lymphocytic
      reaction, which was generally restricted to the subdermal connective tissue.
      However, the study did not address the key outcome of combined vaccination,
      namely immunogenic power. Therefore, further immunological studies are warranted.

PMID- 19863007
TI  - [Chorioptic mange in dairy cattle: a new assessment for its control].
AB  - In the western region of Switzerland, the canton of Freiburg, the clinical and
      subclinical distribution of Chorioptes spp. was studied in 14 stables with
      tethered housing and 10 stables with loose housing, for a total of 667 dairy
      cows. Chorioptes infestations were diagnosed in 22 out of the 24 herds. In the 14
      stables with tethered housing 33.8% of the dairy cows were clinically suspicious
      and 31% were found parasitologically positive. These values were higher than in
      the 10 stables with loose housing that had 26.5% clinically suspicious cases and
      17.8% parasitologically positive cows. The collected clinical findings and
      parasitological diagnoses, as well as the analysed data of Chorioptes
      infestations allowed to determine a reference value for these herds which could
      be used by the practicing veterinarian as an aid in deciding whether to treat the
      whole herd or the single animal. In a cow population an amount of more than 12%
      of cows with clinically manifest Chorioptes spp. infestation reflects a problem
      concerning the whole herd and therefore the whole herd needs to be treated. If
      less than 12% of the cows are visibly infested and no subclinical Chorioptes
      cases are proven, then it only constitutes a problem of single animals and
      therefore can be dealt with individually. The treatment of the herds of two farms
      with tethered housing with Eprinomectin was very effective and showed a long
      lasting 100% antiparasitic effect which lasted more than 92 days after treatment.

PMID- 19863008
TI  - Effect of oral cadmium and zinc application on leukocytes biological activity in
      Japanese quails (Coturnix coturnix japonica).
AB  - Objective of this study was to investigate changes in biological activity of
      blood leukocytes in Japanese quails, caused by zinc and cadmium administration.
      Four groups of Japanese quails were used. Three experimental groups of quails
      were exposed either to Cd (0.12 mg Cd/quail), Zn (4 mg Zn/quail) or a combination
      of Cd and Zn (0.12 mg Cd, 4 mg Zn/quail), which were added daily to the drinking
      water. The fourth group was the control group. The metabolic activity of
      phagocytes and mitogenic activation of lymphocytes to phytohemaglutinine (PHA)
      were determined on day 37, 58 and 118 of exposure. The numbers of peripheral
      blood leukocytes of Japanese quail after cadmium and zinc addition in all groups
      of birds were without significant differences, however, the functional activities
      of phagocytes and lymphocytes in the Cd-group of quails were significantly
      decreased. The metabolic activity of phagocytes decreased significantly at all
      time points analysed (P < 0.05-0.001) in comparison to the control group and the
      Cd-Zn group. Similarly, the response of lymphocytes to PHA activation in the Cd
      exposed group of quails decreased significantly on day 58 and 118 of exposure
      when compared to the control group (P < 0.05) and Zn-group of quails (P < 0.01).
      Zn in combination with Cd eliminated the immunotoxic effect of Cd on metabolic
      activity of phagocytes and improved lymphocyte answer to PHA, when compared to
      the Cd-group on day 58 and 118 of metal administration. The results of the
      present study indicate that cadmium caused a significant decrease of metabolic
      activity of phagocytes and mitogenic activation of lymphocytes in peripheral
      blood of Japanese quails. Simultaneous administration of Zn and Cd eliminated the
      immunotoxic effect of Cd on functional activity of phagocytes and lymphocytes,
      and zinc improved both investigated functional parameters of immune cells.

PMID- 19863009
TI  - The effect of the probiotic strain Enterococcus faecium DSM 7134 in combination
      with natural humic substances on performance and health of broiler chickens.
AB  - The present study investigated the effect of the probiotic strain Enterococcus
      faecium DSM 7134 (2 x 10(7) cfu per g of feed) (probiotic group), natural humic
      substances (7g x kg(-1) feed) (HS group), and the combination of both (probiotic
      + HS group) on the performance, serum biochemistry, and biological activity of
      leucocytes of broiler chickens. Average body weight of chickens in different
      phases as well as throughout the observation period under different treatments
      did not differ significantly. Final body weight and feed conversion ratio (FCR)
      reached in 41 days of trial were 2542.5; 2568.9; 2610.5, 2516.6 g and 1.93; 1.81;
      1.78; 1.88 kg for HS, probiotic, probiotic + HS and control group respectively.
      The best performance variables including the European efficiency index (EEI) were
      observed in the probiotic + HS group, where the effect of the probiotic
      supplementation was improved by HS. There were no significant differences among
      groups in the serum levels of total protein, glucose, cholesterol,
      aminotransferase and phosphorus. A significant decrease of total lipids in the
      probiotic group (P < 0.01) and probiotic + HS group (P < 0.001) groups,
      triglycerides levels in the HS (P < 0.01), probiotic and probiotic + HS (P <
      0.001) groups on day 35, calcium level of the probiotic (P < 0.05) and probiotic
      + HS (P < 0.01) groups on day 41 and alkaline phosphatase levels in the probiotic
      group (P < 0.01) on day 14 were observed in comparison to the control group.
      Significantly higher values of indices of metabolic activity of phagocytes (IMA)
      after 14, 35 and 41 days of the experiment were observed in the probiotic + HS
      group (P < 0.01, P < 0.05) when compared with the control group. No adverse
      health effects were observed in experimental groups The results of the present
      study indicate that HS and E. faecium DSM 7134 had no significant effect on
      performance. However an improvement in FCR and EEI was observed which is believed
      to be due to the significant increase of indices of metabolic activity of
      phagocytes, caused by HS when combined with. E. faecium DSM 7134.

PMID- 19863010
TI  - [Estimation of population genetic parameters for radiographical findings of elbow
      dsyplasia in the Labrador Retriever].
AB  - The aim of this study was the analysis of non-genetic and genetic factors
      influencing elbow dysplasia (ED) in a Labrador retriever population. We analysed
      scores of elbow dysplasia from the official screening programme of the Labrador
      Club Deutschland (LCD) following the protocol of the International Elbow Working
      Group. The data set included X-rays from 2931 Labrador retrievers. These dogs
      were born between 2000 and 2004 and originated from 834 litters and 315 kennels.
      The pedigree file contained 27 305 dogs pertaining to 20 generations. We analysed
      four different traits including ED-Mit as the averaged result of ED scores from
      both elbow joints, ED-Max as the higher score of both elbow joints and ED-links
      and ED-rechts as the ED score of left or right elbow joint. Animal models were
      employed to estimate heritabilities, additive genetic correlation and residual
      correlation using residual maximum likelihood (REML). Significant effects for all
      four ED-traits were gender, month of birth and inbreeding coefficient. The fixed
      effect of birth year showed only significant effects for ED-Mit and ED-rechts.
      Age at examination was not significant. Heritability estimates for ED-Mit were
      0.12 +/- 0.03, for ED-Max 0.11 +/- 0.03 and 0.13 +/- 0.03 for ED-links as well as
      0.07 +/- 0.02 for ED-rechts. Heritability for female dogs was 0.12 +/- 0.03 and
      0.10 +/- 0.03 for male dogs. The additive genetic correlation between ED-links
      and ED-rechts was 1 and the residual correlation 0.64. The heritabilities for ED
      were low to moderate based on models employed here and taking this into
      consideration, selection response will be small when employing phenotypic ED
      scores from breeding animals as the sole selection criterion. Therefore, breeding
      programmes should be supported by breeding values as tools for selection of
      breeding dogs. There was no difference in heritabilities between the mean ED
      score of the joints or the ED score of the joint with the higher ED grade.
      Furthermore, either specific genetic effects from a body side or sex-specific
      genetic effects could be observed for the expression of ED. Dogs showing
      radiographic signs of ED or dogs having been submitted for a surgery due to
      clinical signs of ED have to be precluded from breeding. The veterinary
      practitioner can help to reduce the frequency of dogs exhibiting a genetic
      disposition to ED when the radiographs of the elbow joints of many as possible
      purebred dogs are submitted to the respective dog breeding associations.

PMID- 19863011
TI  - Perosomus elumbis in a black and white German Holstein calf.
AB  - Perosomus elumbis is a rare congenital anomaly of unknown aetiology characterized
      by the aplasia of the lumbosacral spinal cord and vertebrae, mostly associated
      with multiple other malformations of the hind limbs and the urogenital and
      intestinal tract. This report describes a stillborn female German Holstein calf
      showing a complete aplasia of the lumbosacrococcygeal portion of the spinal cord
      and vertebral column. In addition, both hind-limbs exhibited arthrogryposis and
      the musculature was completely replaced by adipose tissue. Furthermore, atresia
      ani and recti, agenesis of one kidney, one adrenal gland, and a hypoplastic and
      atretic female genital tract were detected. The aplasia of the
      lumbosacrococcygeal spinal cord and vertebral column and the other associated
      malformations in the presented case of perosomus elumbis may be the consequence
      of a combined developmental disturbance of the caudal neural tube, notochord and
      paraxial and intermediary mesoderm. However, it remains unclear whether the
      underlying cause is due to an inherited defect or due to an unknown exogenous
      factor disturbing embryogenesis in a critical developmental period.

PMID- 19863012
TI  - [Numerical investigations of the strain adaptive bone remodelling in the
      periprosthetic canine femur].
AB  - After surgical treatment of severe hip diseases with artificial joint prostheses
      aseptic loosening of the implants can occur. Unphysiologic load distribution in
      the periprosthetic femur and stress shielding by the prosthesis can result in
      bone remodelling processes. In particular a cutback of the bone mass is followed
      by an aseptic loosening of the prosthesis. In this context the understanding of
      bone remodelling processes in the prothetically treated femur is of outstanding
      interest for the optimisation of canine hip joint prostheses in the future.
      Therefore the main aim of this sudy was the numerical investigation on the change
      in the load distribution in the canine periprosthetic femur and the resulting
      bone remodelling after implantation of the cemented stem Biomechanique. The
      investigations within this study were carried out using the Finite Element
      Analysis (FEA). The calculated bone density of the periprosthetic femur and the
      evolution of the mass loss show relevant stress shielding areas in different
      analysis regions. Therefore possible regions of aseptic loosening are indicated
      particularly in the proximo-medial femur. The here demonstrated numerical results
      are in agreement with clinical findings. For this reason the FEA-based method is
      a valuable tool for the prediction of bone remodelling processes.

PMID- 19863013
TI  - Neonatal health in calves--comprehensive solutions for complex enteric disorders.

PMID- 19863014
TI  - [Quantified objectives for the next law related to public health policy].

PMID- 19863015
TI  - [An individual and collective approach to the continuity of care].
AB  - Anthony Giddens' theory of structuring offers a comprehensive rationale that
      explains and allows understanding of the duality of individual and collective
      action. It takes into account both organisational structures and individual
      agents' actions and, most importantly, it highlights the underlying dynamics of
      the "duality of structure". Gidden's theory is the cornerstone of this study on
      the production and the reproduction of problems in the continuity of oncological
      care within the Quebec healthcare system. By using it, one can identify the
      contexts within which action takes place and distinguish the strategies social
      agents implement in order to deal with the situations generated by those
      contexts. Finally, one can describe the consequences for the health care system
      as a whole. The aim of this article is to show how Giddens' theory of structuring
      can be used for the study of socio-organizational phenomena.

PMID- 19863016
TI  - [Personnel at risk for occupational blood exposure in a university hospital in
      West Algeria].
AB  - The accidental occupational exposure of health care workers to blood or other
      body fluids after skin injury or mucous contact, constitutes a risk for the
      transmission of the hepatitis B virus (HBV), hepatitis C virus (HCV) or human
      immunodeficiency viruses (HIV). This paper presents the results of a survey
      carried out over two years (January 2005 - December 2006) on reported
      occupational blood exposures (OBE). The study aimed to determine incidence,
      workers and professional categories at risk, and circumstances of OBE occurrence
      in order to identify avoidable cases and to orient prevention measures. Personal
      and professional data, immunization status, circumstances of OBE incidents,
      preventive measures, workers' behaviour post-exposure, and serology surveillance
      were collected. 108 exposures were reported by 70 women and 38 men. In total, 44
      accidents were reported in 2005, and 64 in 2006. Needle stick injuries
      represented 81% of cases. Source patient serology was unknown in most of the
      cases, negative in 9% of cases and positive in 10% of cases. 62% of exposed
      health workers received immediate serology, follow up and screening as of the
      first day of exposure, 12% after 3 months and 36% after 6 months. No
      seroconversion case was noted. Cleaning staff and hygiene workers are at high
      risk of blood contamination as well as nurses, and more than one-third of
      injuries occurred because of mismanagement of healthcare waste produced in the
      hospital environment, where needles were not disposed of appropriately in a hard
      container. Thus, 41.66% of injuries could be avoided if objects were thrown away
      correctly in specific containers. It is urgent to raise awareness of health care
      personnel and strengthen adherence to standard precautions as well as to provide
      suitable containers for the collection and disposal of needles and sharp objects.

PMID- 19863017
TI  - [Cholera epidemics in Mali between 1995 and 2004].
AB  - INTRODUCTION: Cholera represents a public health problem in developing countries
      like Mali. AIM: This work aims to describe the characteristics of the cholera
      epidemics which occurred in Mali between 1995 and 2004. METHOD: A retrospective
      survey was conducted within the Division of the fight against the diseases of
      epidemic potential and the Institute of Public Health and Research of the
      Ministry of Health of Mali. Individual medical records tracking the follow-up of
      patients as well as the registers of these structures were used as sources to
      collect data for the study. RESULTS: There were 12,176 cases of cholera recorded,
      including 1,406 deaths, from 1995 to 2004. Cholera outbreaks in Mali have been a
      regular occurrence every year since 2001. The regions of Mopti and Segou seem to
      be the most impacted by these epidemics. The lethal rates were higher than 1% at
      the time of each of these epidemics during this period. Vibrio cholerae O: 1,
      biotype El Tor were responsible for the epidemics, and the serotype Ogawa was
      prevalent. CONCLUSION: Cholera epidemics have been constant in Mali since the
      beginning of the 21st century in spite of the efforts which have been made to
      prevent and control them. A rigorous analysis of the factors which support this
      persistence and appropriate measures are essential to reverse cholera in this
      country.

PMID- 19863018
TI  - [Evaluation of knowledge, attitudes and practices in the health care setting in
      Morocco with regard to hepatitis B and C].
AB  - The purpose of this study was to evaluate practices and knowledge on infectious
      hazards, to determine the prevalence of viral hepatitis B and C related to
      occupational blood exposures among health care workers, and to propose a
      prevention policy. This descriptive epidemiological survey, which is multicentric
      and cross-cutting, was carried out in 2005 in four Moroccan cities. 1562 health
      care workers were contacted and 1002 accepted to reply to the questionnaire
      (64.1%). The mean age was 39.5 +/- 6.8 years and length of service 12.6 +/- 8.3
      years. Blood was identified as the product most handled by workers (91.3%),
      followed by dirty linen and hospital waste. The most frequently used instruments
      reported were hollow needles (77.9%), followed by lancets. Re-sheathing used
      needles was practiced by 47.3% of the personnel. Nurses, assistants and support
      staff have insufficient knowledge on how viral hepatitis B and C is transmitted.
      Only 47.4% of personnel were adequately vaccinated against hepatitis B. Post
      vaccines serology was carried out on only 2.7% of the vaccinated staff. During
      the last twelve months, 62.8% of the persons were victim to at least one
      occupational blood exposures of which 8.3% were reported. Universal precautions
      are not widely known or applied: only 24.4% wore gloves for invasive acts and 63%
      correctly disinfected their hands. Viral hepatitis B and C hazards in healthcare
      facilities are not sufficiently taken account. The recent creation of
      occupational health services in hospital facilities should contribute to improve
      working conditions, provide for mandatory vaccination of hospital employees
      against viral hepatitis B, and improve and increase information and education on
      hazards related to occupational blood exposures for healthcare personnel.

PMID- 19863019
TI  - [Mobile screening unit for HIV and STI among seasonal workers in the ski resorts
      of Savoy, France: interest and perspectives].
AB  - Seasonal workers in 11 Savoy ski resorts were screened for HIV and sexually
      transmitted infections by a special mobile unit set up by the Chambery hospital.
      The service is free and anonymous. In order to evaluate this initiative,
      information was collected via a survey conducted of the 539 people who used the
      services of the mobile unit between February 1st and April 1st 2007 through the
      use of a questionnaire. In addition, sixty-three interviews were conducted with
      local, regional and national partners. Ninety-two percent of the clients were
      seasonal workers and their main request (95%) was for HIV and STI testing. None
      tested positive for HIV, and only three had an STI. This unit is the main entry
      point into the health system for this population. The results of the evaluation
      report support the recommendation for the mobile unit to be positioned as an
      important social focal point for seasonal workers, providing the prevention for
      high-risk behaviors, closely linked to the structures of "seasonal workers homes"
      and employing seasonal workers peer educators.

PMID- 19863020
TI  - [Contribution of supplementation by spirulina to the performance of school
      children in an introductory course in Dakar (Senegal)].
AB  - Senegal initiated a program to improve the nutritional status of school-age
      children with the use of spirulina. The objective of this study was to evaluate
      the effects of spirulina on academic performance of school children in the
      municipality of Dakar, Senegal. The evaluation was conducted as a prospective
      study, comparing school performance of schoolchildren from public elementary
      schools located in three National Education Departments of Dakar (before
      supplements, during and after). The study population consisted of students from
      six schools randomly selected among the 100 who were in the program. We included
      all children with agreement of their parent or guardian, and those who rejected
      the spirulina were not included. Supplemental feeding with spirulina was given to
      young children during two months (from mid-April to mid June 2005). Over these 60
      days, the students took a daily dose of 2 grams of spirulina mixed with 10g of
      honey to make the taste acceptable. The data on age, gender and monitoring of
      school performance (i.e. the average compositions of the second and third
      quarters) were collected. Mean differences in grades between second quarter and
      third quarter (after two months of supplementation) were analyzed and compared by
      the paired student test. The sample size was a total of 549 schoolchildren: 273
      (49.72%) were girls, and 276 (50.28%) boys. The mean age was 91 months [90.29
      91.71]. The average of 2rd quarter marks before supplementation was 5.17 out of
      10 IC = [4.99-5.35] and the same for the 3rd quarter after two months of
      supplementation was 5.78 out of 10 IC = [5.59-5.97]. The mean difference between
      pupils' marks at the 3rd and the 2nd trimester was 0.59 (p <-- 0.0001). After two
      months of supplemental feeding, the academic performance of the children was
      improved.

PMID- 19863022
TI  - [Evaluation of health education trainings developped between 2005 and 2007 in the
      North].
AB  - The regional health education plan (SREPS) in Nord Pas-de-Calais opened a window
      for the Regional Directorate of Health and Social Affairs (DRASS) to initiate and
      engage in a process to reflect on the development of health education training.
      The Regional Committee of Health Education (CRES) has developed and led a
      regional project on health education training since 2005, financed by the
      National Institute of Prevention and Health Education (Inpes). At the request of
      the Inpes, the 3 year duration of the project was evaluated in 2008. The results
      provide on opportunity for conducting analyses and drawing some interesting
      conclusions such as: to construct the profile of the 572 people trained, to
      evaluate the impact of such training on the locally programmed health actions and
      on actors' skills, and to analyse the educational process developed through the
      sessions. This work initiates a new regional questioning and exploration of
      continuing education in the field of health education and promotion.

PMID- 19863021
TI  - [Complex management of partnerships during a health promotion campaign].
AB  - This article discusses an analysis of partnerships in the context of health
      promotion. The 5/30 Health Challenge, or "Defi Sante 5/30", is a campaign to
      promote healthy eating habits in Quebec. The authors employ this as a case study
      in order to 1) describe the actors and the nature of their involvement during the
      campaign's development, design and dissemination; 2) illustrate the interaction
      of these actors during the conceptualization and rollout of the campaign; 3)
      propose a paradigm that supports the identification of factors that contribute to
      or impede partner relationships. The "Defi Sante 5/30" example demonstrates that
      the creation and maintenance of a partnership network depends on the following
      key factors: dialogue between partners and the organization responsible for the
      campaign; the participation of partners at every stage of the campaign (no matter
      how many there are); allocation of sufficient time for the conceptualization of
      campaign materials. Dialogue between partners and the central organizer must be
      guaranteed through the establishment and use of a managerial contract that
      clearly outlines the role of each actor in the campaign. Further, the partners'
      activities during the campaign should be regulated through both a formal
      agreement and a code of ethics. Any campaign's efficiency is directly linked to
      these factors, among others. The study of partnerships between public, public
      private, and private organizations within the framework of health promotion
      campaigns, thus, merits further study. In addition, to maintain alliances with
      partners, it is important to demonstrate the benefits of such arrangements to
      each partner and to equally ensure the contributions of each, be they public,
      private, media, or community-based organizations.

PMID- 19863023
TI  - [The law and discrimination: exploring the question of illegitimacy with regard
      to restrictions imposed on foreigner's rights to care].

PMID- 19863024
TI  - [The future of health: is a quiet revolution still possible?].

PMID- 19863025
TI  - NMC under fire for lack of support on swine flu surge.

PMID- 19863026
TI  - Counting the change.

PMID- 19863027
TI  - Trusts must tackle all forms of negative behaviour between staff.

PMID- 19863028
TI  - Using NHS resources effectively to improve the ward environment for patients and
      staff.
AB  - When the nursing team on the high dependency unit at St James' Hospital, Leeds,
      moved to their new unit they discovered that aspects of the environment were
      notworking to the best advantage of patients, visitors and staff. This article
      outlines the process of identifying and assessing the scope of the issues and
      formulating an improvement plan. It concludes by sharing the lessons the team
      learnt, particularly in terms of making better use of existing resources and
      putting patient experience at the centre of the process.

PMID- 19863029
TI  - Is it true that best practice for administering i.v. flushes/boluses is via a
      Luer lock syringe as opposed to a Luer slip?

PMID- 19863030
TI  - Looking beyond bullying to assess the impact of negative behaviours on healthcare
      staff.
AB  - BACKGROUND: Evidence suggests that bullying behaviours are common in the NHS.
      Various health organisations in the area studied had experienced problems with
      negative behaviours between staff and it was decided that research was needed.
      AIM: To assess and analyse negative behaviours experienced and/or witnessed by
      primary healthcare staff. METHOD: A mainly quantitative questionnaire was sent to
      random samples of staff in two primary care trusts, and a small "contact group"
      who had sought help because of negative behaviours. RESULTS: In PCT A 63% and in
      PCT B 53% of respondents considered they had experienced and/or witnessed some
      level of negative behaviour in the previous 12 months. Most of the behaviour was
      described as incivility (67% in the random sample overall). Some of the
      incivility was also perceived as bullying but some was not. Regardless of
      perception, similar levels of negative effect were experienced. DISCUSSION:
      Focusing on bullying alone and on frequency of behaviour misses part of the
      picture; what counts is the negative experience. CONCLUSION: Organisations need
      to take a broader view and prevent the full range of damaging negative behaviour
      between staff.

PMID- 19863031
TI  - Piloting the introduction of personal health plans for people with long term
      conditions.
AB  - This is the third article in a three part series on personalised care planning
      for people with long term conditions. It describes the work carried out in NHS
      East of England to develop and pilot personal health plans, with details of the
      NHS South West Essex Community Services pilot site.

PMID- 19863032
TI  - Smoking cessation 2: targeting, engaging and supporting hard to reach groups.
AB  - This second in a two part unit on smoking cessation discusses ways to engage and
      support hard to reach groups. Part 1 outlined the various options available to
      help smokers who want to quit, such as behavioural support and pharmacotherapy.

PMID- 19863034
TI  - Health and safety culture creates unnecessary fears.

PMID- 19863033
TI  - On why trusts must act now to deliver the maternity strategy.

PMID- 19863035
TI  - Urologic nurses thriving under pressure.

PMID- 19863036
TI  - Improving practice: establishing processes to query clinical data warehouses.

PMID- 19863037
TI  - Nurses exchanging information: understanding electronic health record standards
      and interoperability.
AB  - The complexity in adopting health information technology (IT) standards is not
      from lack of standards. Rather, there are a vast number of standards that overlap
      and some that are missing. The objective of this article is to provide nurses
      with an understanding of the importance of the National Health IT Agenda and be
      empowered to influence the processes to ensure nursing is represented. Several
      aspects include harmonization and adoption of standards necessary to achieve
      interoperability, and the strategies for nursing leaders to advocate for adoption
      of those standards.

PMID- 19863038
TI  - Protecting patient information in an electronic age: a sacred trust.
AB  - Keeping pace with changes in electronic technologies and their implications in
      terms of privacy is a challenge. The purpose of this article is to provide an
      overview of new technologies and remind nurses of their responsibilities in
      safeguarding patient information.

PMID- 19863039
TI  - Terminology use in electronic health records: basic principles.
AB  - Electronic health records (EHRs) are a cost-saving and environmentally friendly
      means for documenting patient care and improving patient safety, quality, and
      evidence-based practice. Standardized clinical classification systems and
      terminologies are essential ingredients of the EHR. Their selection must be
      driven by a clear understanding of requirements for their use and application.
      This article describes the principle uses of clinical information and motives for
      consistency in practice, and provides a distinction between classification
      systems and reference terminologies for clinical settings.

PMID- 19863040
TI  - Introducing a computer-based electronic record: perceptions of clinicians.
AB  - This article presents information that leaders must understand as technology in
      health care continues to evolve. One project is described in which staff managers
      were surveyed to objectively assess departmental and organizational readiness to
      implement a computer-based electronic record system.

PMID- 19863041
TI  - Essential steps in super user education for ambulatory clinic nurses.
AB  - Pre-implementation and education steps for ambulatory care nurses chosen as super
      users are described in this article. Those chosen as super users supported a new
      electronic medical record (EMR) within a large academic medical center with more
      than 200 health care specialty clinics. Essential steps prepared these super
      users to integrate the EMR into their daily workflows.

PMID- 19863042
TI  - Infusing clinical decision support interventions into electronic health records.
AB  - Electronic medical records and health records provide a variety of clinical
      decision support interventions to guide or support the clinical user. These
      interventions are design features to guide users in next steps, offer useful
      evidence-based knowledge, or provide patient information relevant to a decision.

PMID- 19863043
TI  - An evaluation process for an electronic bar code medication administration
      information system in an acute care unit.
AB  - The purpose of this case study is to present an evaluation process and
      recommendations for addressing the gaps found with the implementation of a new
      bar code medication administration (BCMA) technology in a busy acute care
      hospital unit. The case study analyzes workflow procedures associated with
      administration of medications in an inpatient labor and delivery care unit before
      and one year after implementation of BCMA technology. The comparison reveals a
      twofold increase in workflow procedures for nursing staff because of the new
      technology. System gaps are identified from a nursing user's perspective, and
      recommendations are offered to close those gaps.

PMID- 19863044
TI  - Reminder systems to reduce the duration of indwelling urinary catheters: a
      narrative review.
AB  - Catheter-associated urinary tract infection (CAUTI) is a common and costly
      problem for hospitalized patients. Policymakers have taken notice of the
      importance of these infections, and changes to the prospective payment rules of
      Medicare, Medicaid, and many additional third-party payers have been implemented
      to hold hospitals accountable for the delivery of poor quality health care
      services. As key members of the health care team, nurses must be prepared to
      utilize evidence-based practices to prevent CAUTI in hospitalized patients. This
      article describes several variable-technology interventions to remind clinicians
      to remove unnecessary urinary catheters and proposes potential roles for nursing
      informatics in the prevention of CAUTI in hospitalized adults.

PMID- 19863045
TI  - Vitamin C with metabolites: additional analysis suggests favorable changes in
      oxalate.
AB  - A previously published randomized trial found a significant difference in the
      proportion of individuals experiencing oxalate reduction with a vitamin C with
      metabolites product compared with ascorbic acid (vitamin C). This represented a
      notable finding, which argued against the possibility of a chance finding due to
      the design and consistency of results. However, these researchers believed it was
      necessary to further analyze this study to continue to garner more insight on the
      strength or weakness of original findings. All favorable, neutral, and non
      favorable changes of 24-hour oxalate from the previous clinical trial were
      grouped. Oxalate was considered to "decrease" or "increase" with each
      intervention only if a 10% or larger change occurred in the 24-hour oxalate
      baseline value when taking one product compared to another. A greater proportion
      of subjects taking both products at different time periods experienced favorable
      oxalate changes with vitamin C with metabolites product compared to ascorbic
      acid. If this reflects the true clinical scenario, this would represent an
      important clinical finding on a population level because at least 20% more
      individuals would experience a more favorable change. Regardless, this further
      analysis continues to suggest that the original observations were valid and could
      have positive clinical implications for some patients.

PMID- 19863046
TI  - Testosterone for the treatment of hypoactive sexual desire disorder: part II.
AB  - There are no testosterone products approved for women by the Food and Drug
      Administration (FDA). Testosterone is often prescribed "off-label" to women for
      the treatment of hypoactive sexual desire disorder (HSDD).

PMID- 19863047
TI  - Getting ready for certification: taking the challenge.

PMID- 19863048
TI  - Enhancement of antitumor activities in sulfated and carboxymethylated
      polysaccharides of Ganoderma lucidum.
AB  - Two water-soluble derivatives, sulfated and carboxymethylated Ganoderma lucidem
      polysaccharides, coded as S-GL and CM-GL, were prepared using derivatization of
      water-insoluble polysaccharides (GL-IV-I) extracted from the fruit body of G.
      lucidem . The degree of substitution (DS) of S-GL and CM-GL was 0.94 and 1.09,
      respectively. The weight-average molecular mass (Mw) of GL-IV-I, S-GL, and CM-GL
      was determined with light scattering to be 13.3x10(4), 10.1x10(4), and 6.3x10(4),
      respectively. S-GL and CM-GL inhibited the in vitro proliferation of Sarcoma 180
      (S-180) tumor cells in a dose-dependent manner, with an IC50 value of 26 and 38
      microg/mL, respectively. They also inhibited the growth of S-180 solid tumors
      implanted in BALB/c mice, with low toxicity to the animals. Flow cytometric
      studies revealed that treatment of S-GL and CM-GL with S-180 tumor cells could
      mediate the cell-cycle arrest in the G2/M phase. The expression of Bax increased,
      and the expression of Bcl-2 decreased dramatically, as shown by immuno
      histochemical staining of S-180 tumor tissue excised from the animals. The
      sulfated and carboxmethylated groups in the polysaccharides played an important
      part in enhancing their antitumor activities, leading to the potential to be
      developed into antitumor drugs.

PMID- 19863049
TI  - Intake of 1-deoxynojirimycin suppresses lipid accumulation through activation of
      the beta-oxidation system in rat liver.
AB  - It was recently shown that administration of 1-deoxynojirimycin (DNJ) extracted
      from mulberry suppresses an increase in postprandial blood glucose in humans.
      These findings are of interest, but other physiological functions of DNJ are
      unknown. This study examined the effects of oral administration of DNJ (1 mg/kg
      of body weight/day) or mulberry extracts enriched in DNJ (meDNJ; 100 or 200 mg of
      extract/kg of body weight/day, equivalent to 0.53 or 1.06 mg of DNJ/kg of body
      weight/day) in male Sprague-Dawley rats for 4 weeks. DNJ and meDNJ enhanced
      expression of adiponectin mRNA in white adipose tissue; increased plasma
      adiponectin levels, enhanced expression of AMPK mRNA, activated the beta
      oxidation system, and suppressed lipid accumulation in the liver. Intake of DNJ
      and meDNJ did not cause hepatic dysfunction and led to a reduction of oxidative
      stress. These results indicate the efficacy and safety of DNJ and meDNJ.

PMID- 19863050
TI  - From serendipity to rational antituberculosis drug discovery of mefloquine
      isoxazole carboxylic acid esters.
AB  - Both in vitro and in vivo metabolism studies suggested that 5-(2,8
      bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl
      ester (compound 3) with previously reported antituberculosis activity is rapidly
      converted to two metabolites 3a and 3b. In order to improve the metabolic
      stability of this series, chemistry efforts were focused on the modification of
      the oxymethylene linker of compound 3 in the present study. Compound 9d with an
      alkene linker was found to be both more metabolically stable and more potent than
      compound 3, with a minimum inhibitory concentration (MIC) of 0.2 microM and 2.6
      microM against replicating and nonreplicating Mycobaterium tuberculosis,
      respectively. These attributes make 9d an interesting lead compound. A number of
      modifications were made to the structure of 9d, and a series of active compounds
      were discovered. Although some neurotoxicity was observed at a high dosage, this
      new series was endowed with both improved in vitro anti-TB activity and metabolic
      stability in comparison to compound 3.

PMID- 19863051
TI  - Proteomic effects of potential endocrine-disrupting compounds.

PMID- 19863052
TI  - Plasmonic ratchet wheels: switching circular dichroism by arranging chiral
      nanostructures.
AB  - We demonstrate circular dichroism (CD) in the second harmonic generation (SHG)
      signal from chiral assemblies of G-shaped nanostructures made of gold. The
      arrangement of the G shapes is crucial since upon reordering them the SHG-CD
      effect disappears. Microscopy reveals SHG "hotspots" assemblies, which originate
      in enantiomerically sensitive plasmon modes, having the novel property of
      exhibiting a chiral geometry themselves in relation with the handedness of the
      material. These results open new frontiers in studying chirality.

PMID- 19863053
TI  - Evaporation dynamics of microdroplets on self-assembled monolayers of dialkyl
      disulfides.
AB  - We present a study of the static wettability and evaporation dynamics of sessile
      microdroplets of water on self-assembled monolayers (SAMs) prepared with
      unsymmetric dialkyl disulfides CH(3)-(CH(2))(11+m)-S-S-(CH(2))(11)-OH (m = 0, +/-
      2, +/- 4, +/- 6) on gold-covered mica. The advancing and receding contact angles
      decrease linearly with increasing hydrophilicity of the SAM. The latter was
      changed either via the molar ratio or via the chain length of the hydroxyl
      terminated alkyl chains in the monolayer. In contrast to SAMs made of thiols, the
      contact angle hysteresis was 10 degrees for all disulfides, irrespective of their
      chain lengths. During evaporation of single droplets, a transition from pinning
      to constant contact angle mode was observed. The transition time between the
      modes increases with the surface hydrophilicity, leading to longer pinning. This
      way, the time for complete droplet evaporation decreases by approximately 30%
      owing to the fact that during pinning the overall droplet area stays large for a
      longer time. For single droplets the measured total evaporation times agree well
      with the calculated ones, showing the validity of the standard evaporation model
      for both evaporation modes. In contrast to the results for single droplets, many
      droplets with different initial volumes show a power-law dependence on the total
      evaporation time with an exponent different from 1.5 as expected from the
      standard model. For disulfides with m not equal 0, the exponent is in the range
      of 1.40-1.47 increasing with the surface hydrophilicity. For the SAMs with m = 0
      the exponent increases up to 1.61 for the most hydrophilic surface. We explain
      this deviation from the standard evaporation model with the presence of a liquid
      precursor film around the droplet, which either enhances or decelerates
      evaporation. Our results suggest that SAMs of dialkyl disulfides offer the
      possibility to tune the wettability of gold surfaces in a more controlled way
      than thiols do.

PMID- 19863054
TI  - Losartan-antioxidant hybrids: novel molecules for the prevention of hypertension
      induced cardiovascular damage.
AB  - We report the first examples of a new series of antioxidant-sartan hybrids (AO
      sartans), which were made by adding an antioxidant fragment to the hydroxymethyl
      side chain of losartan. Experiments performed in cultured cells demonstrate that
      these new hybrids retain the ability to block the angiotensin II effect with
      increased antioxidant ability. In hypertensive rats, these compounds show
      properties that suggest they may be more useful than losartan for controlling
      hypertension and preventing hypertension-induced cardiovascular damage.

PMID- 19863055
TI  - Novel compounds designed as antistress agents.
AB  - Agents against biologic stress were designed, containing GABA esterified with
      lorazepam and amidated with (R)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic
      acid (5) or 3,5-di-tert-butyl-4-hydroxybenzoic acid (6). Compounds 5 and 6
      inhibited lipid peroxidation, IC(50) 1.1 and 24 microM. Oxidative damage
      accompanied stress, 5 and 6 reduced radical attack, uropepsinogen, and
      morphological changes. Stress increased drug metabolism. Treatment with 5 reduced
      cytochrome P450 and N-demethylation of erythromycin, 35 and 40%. Compounds 5 and
      6 decreased lipidemic indices of hyperlipidemic rats 40-63%.

PMID- 19863056
TI  - Preparation of biocompatible sterically stabilized latexes using well-defined
      poly(2-(methacryloyloxy)ethyl phosphorylcholine) macromonomers.
AB  - A range of well-defined methacrylic macromonomers based on the biomimetic monomer
      2-(methacryloyloxy)ethyl phosphorylcholine (MPC) were synthesized by atom
      transfer radical polymerization (ATRP) in alcoholic media using 2
      (dimethylamino)ethyl-2-bromoisobutyrylamide. This tertiary amine-functionalized
      initiator was used to produce homopolymer precursors of various chain lengths via
      ATRP. These polymerizations were relatively well controlled (M(w)/M(n) < or =
      1.30), provided that the target degree of polymerization (DP) did not exceed 30.
      For higher target DPs, polymerization was only poorly controlled and
      characterized by broad molecular weight distributions (M(w)/M(n) = 1.50-2.31).
      The tertiary amine end-group of each nearly monodisperse homopolymer precursor
      was then quaternized using 4-vinylbenzyl chloride (4-VBC) to afford the
      corresponding styrene-functionalized macromonomers. PMPC(30) macromonomer proved
      to be an effective reactive steric stabilizer for the formation of polystyrene
      latexes when employed at 10 w/w % on the basis of the styrene monomer. Nearly
      monodisperse submicrometer-sized and micrometer-sized latexes were prepared by
      aqueous emulsion and alcoholic dispersion polymerization, respectively, as judged
      by scanning electron microscopy and dynamic light scattering studies. In
      contrast, attempted alcoholic dispersion polymerization conducted either in the
      presence of the PMPC(30) homopolymer precursor or in the absence of any
      macromonomer always resulted in macroscopic precipitation. Such control
      experiments confirmed the importance of the terminal styrene groups on the
      macromonomer chains for successful latex formation. FTIR spectroscopy indicated
      the presence of the PMPC(30) macromonomer within the polystyrene latex, and XPS
      studies indicated that these stabilizer chains are located at (or very near) the
      latex surface, as expected. Using PMPC(20) and PMPC(10) macromonomers for the
      alcoholic dispersion polymerization of styrene led to latexes with substantially
      broader size distributions compared to those produced using the PMPC(30)
      macromonomer under the same conditions. Finally, these new sterically stabilized
      latexes exhibit excellent freeze-thaw stability and salt tolerance.

PMID- 19863057
TI  - Inhibitors for human glutaminyl cyclase by structure based design and
      bioisosteric replacement.
AB  - The inhibition of human glutaminyl cyclase (hQC) has come into focus as a new
      potential approach for the treatment of Alzheimer's disease. The hallmark of this
      principle is the prevention of the formation of Abeta(3,11(pE)-40,42), as these
      Abeta-species were shown to be of elevated neurotoxicity and likely to act as a
      seeding core leading to an accelerated formation of Abeta-oligomers and fibrils.
      Starting from 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea,
      bioisosteric replacements led to the development of new classes of inhibitors.
      The optimization of the metal-binding group was achieved by homology modeling and
      afforded a first insight into the probable binding mode of the inhibitors in the
      hQC active site. The efficacy assessment of the hQC inhibitors was performed in
      cell culture, directly monitoring the inhibition of Abeta(3,11(pE)-40,42)
      formation.

PMID- 19863058
TI  - Sphingomyelinase-induced phase transformations: causing morphology switches and
      multiple-time-domain ceramide generation in model raft membranes.
AB  - Sphingomyelinase (SMase) has been shown to be involved in a variety of cell
      regulation processes by reorganizing the cell membrane morphology. Here we report
      that SMase can induce a reaction-induced and a solvent-mediated phase
      transformation, causing switches of three stationary membrane morphologies and
      multiple-time-domain ceramide generation in model raft membranes. The reaction
      induced phase transformation, triggered by the addition of SMase, transforms a
      pre-existing morphology to a long-lasting intermediate morphology with coexisting
      ceramide-enriched (Cer-enriched) and sphingomyelin-enriched (SM-enriched)
      domains. Solvent-mediated phase transformation ultimately transforms all of the
      SM-enriched domains of the intermediate morphology into Cer-enriched domains.
      Labeled SMase experiments suggest that the intermediate morphology results from
      physical trapping of SM in the SM-enriched domains, which are found to be
      relatively inaccessible to SMase. The characterization results from confocal
      fluorescence imaging show that the trigger of the solvent-mediated phase
      transformation is the formation of a 3-D feature rich in SMase, sphingomyelin,
      and ceramide. This 3-D feature is hypothesized as a slowly nucleating SMase
      enriched phase, where SMase processes sphingomyelin more efficiently. The
      disparate time-scales of the formation of these SMase-features and the SM
      enriched domains allow for the development of a significant duration of the
      middle intermediate morphology between the two transformations. The results show
      that SMase can be actively involved in the lipid membrane phase changes. The
      multistage morphology evolution is not only due to membrane-compositional changes
      caused by SMase, but also due to the selective binding of SMase, and the SMase's
      special phase behavior during the solvent-mediated phase transformation.

PMID- 19863059
TI  - Preparation of hydantoins by catalytic oxidative carbonylation of alpha-amino
      amides.
AB  - Hydantoins can be synthesized from the corresponding amino amides employing
      oxidative catalytic carbonylation using W(CO)(6) as the catalyst, I(2) as the
      oxidant, CO as the carbonyl source, and DBU as base. Secondary amides afford the
      hydantoins in good to excellent yields, which decrease as the steric bulk of the
      N-alkyl substituent increases.

PMID- 19863060
TI  - How the nature of triphenylamine-polyene dyes in dye-sensitized solar cells
      affects the open-circuit voltage and electron lifetimes.
AB  - Three donor-linker-acceptor triphenylamine-based cyanoacrylic acid organic dyes
      used for dye-sensitized solar cells (DSCs) have been examined with respect to
      their effect on the open-circuit voltage (V(oc)). Our previous study showed a
      decrease in V(oc) for DSCs based on dyes with increased molecular size (increased
      linker conjugation). In the present study, we investigate the origin of V(oc)
      with respect to (i) conduction band (E(CB)) positions of TiO(2) and (ii) degree
      of recombination between electrons in TiO(2) and electrolyte acceptor species at
      the interface. These parameters were studied as a function of dye structure, dye
      load, and I(2) concentration. Two types of behavior were identified: the smaller
      polyene dyes show a surface-protecting effect preventing recombination upon
      increased dye loading, whereas the larger dyes enhance the recombination. How the
      different dye structures affect the recombination is discussed in terms of dye
      surface blocking and intermolecular interactions between dyes and electrolyte
      acceptor species.

PMID- 19863061
TI  - Dimer shape anisotropy: a nonspherical colloidal approach to omnidirectonal
      photonic band gaps.
AB  - Theoretical calculations of the photonic band gap forming properties are reported
      for a class of colloidal dimer-based structures with similarity to zinc blende
      and which map onto diamond or opalline face-centered cubic structures at the
      extrema in shape parameters. Inspired by the range of nonspherical building
      blocks for self-assembly synthesized using seeded emulsion polymerization and sol
      gel techniques, we explore in particular the band structures as a function of
      dimer lobe symmetry and the degree of lobe interpenetration for tangent dimers.
      Complete photonic band gaps were observed between the second and third, fifth and
      sixth, or eighth and ninth bands for various shape classes. As well, select
      inverted and direct dimer-based structures showed two complete band gaps
      simultaneously.

PMID- 19863062
TI  - Interaction of the Tim44 C-terminal domain with negatively charged phospholipids.
AB  - The translocation of proteins from the cytosol into the mitochondrial matrix is
      mediated by the coordinated action of the TOM complex in the outer membrane, as
      well as the TIM23 complex and its associated protein import motor in the inner
      membrane. The focus of this work is the peripheral inner membrane protein Tim44.
      Tim44 is a vital component of the mitochondrial protein translocation motor that
      anchors components of the motor to the TIM23 complex. For this purpose, Tim44
      associates with the import channel by direct interaction with the Tim23 protein.
      Additionally, it was shown in vitro that Tim44 associates with acidic model
      membranes, in particular those containing cardiolipin. The latter interaction was
      shown to be mediated by the carboxy-terminal domain of Tim44 [Weiss, C., et al.
      (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 8890-8894]. The aim of this study was to
      determine the precise recognition site for negative lipids in the C-terminal
      domain of Tim44. In particular, we wanted to examine the recently suggested
      hypothesis that acidic phospholipids associate with Tim44 via a hydrophobic
      cavity that is observed in the high-resolution structure of the C-terminal domain
      of the protein [Josyula, R., et al. (2006) J. Mol. Biol. 359, 798-804]. Molecular
      dynamics simulations suggest that (i) the hydrophobic tail of lipids may interact
      with Tim44 via the latter's hydrophobic cavity and (ii) a region, located in the
      N-terminal alpha-helix of the C-terminal domain (helices A1 and A2), may serve as
      a membrane attachment site. To validate this assumption, N-terminal truncations
      of yeast Tim44 were examined for their ability to bind cardiolipin-containing
      phospholipid vesicles. The results indicate that removal of the N-terminal alpha
      helix (helix A1) abolishes the capacity of Tim44 to associate with cardiolipin
      containing liposomes. We suggest that helices A1 and A2, in Tim44, jointly
      promote the association of the protein with acidic phospholipids.

PMID- 19863063
TI  - Yeast display evolution of a kinetically efficient 13-amino acid substrate for
      lipoic acid ligase.
AB  - Escherichia coli lipoic acid ligase (LplA) catalyzes ATP-dependent covalent
      ligation of lipoic acid onto specific lysine side chains of three acceptor
      proteins involved in oxidative metabolism. Our lab has shown that LplA and
      engineered mutants can ligate useful small-molecule probes such as alkyl azides (
      Nat. Biotechnol. 2007 , 25 , 1483 - 1487 ) and photo-cross-linkers ( Angew.
      Chem., Int. Ed. 2008 , 47 , 7018 - 7021 ) in place of lipoic acid, facilitating
      imaging and proteomic studies. Both to further our understanding of lipoic acid
      metabolism, and to improve LplA's utility as a biotechnological platform, we have
      engineered a novel 13-amino acid peptide substrate for LplA. LplA's natural
      protein substrates have a conserved beta-hairpin structure, a conformation that
      is difficult to recapitulate in a peptide, and thus we performed in vitro
      evolution to engineer the LplA peptide substrate, called "LplA Acceptor Peptide"
      (LAP). A approximately 10(7) library of LAP variants was displayed on the surface
      of yeast cells, labeled by LplA with either lipoic acid or bromoalkanoic acid,
      and the most efficiently labeled LAP clones were isolated by fluorescence
      activated cell sorting. Four rounds of evolution followed by additional rational
      mutagenesis produced a "LAP2" sequence with a k(cat)/K(m) of 0.99 muM(-1) min(
      1), >70-fold better than our previous rationally designed 22-amino acid LAP1
      sequence (Nat. Biotechnol. 2007, 25, 1483-1487), and only 8-fold worse than the
      k(cat)/K(m) values of natural lipoate and biotin acceptor proteins. The kinetic
      improvement over LAP1 allowed us to rapidly label cell surface peptide-fused
      receptors with quantum dots.

PMID- 19863064
TI  - Lysine-60 in copper chaperone Atox1 plays an essential role in adduct formation
      with a target Wilson disease domain.
AB  - The mechanism by which the human copper (Cu) chaperone Atox1 delivers Cu to metal
      binding domains of Wilson disease (WD) protein for insertion into cuproenzymes is
      unclear. Using near-UV circular dichroism as a new tool to probe chaperone-target
      interactions, in combination with gel filtration and molecular dynamics
      simulations, we here demonstrate that Atox1 forms a stable Cu-dependent adduct
      with the fourth metal-binding domain of WD (WD4). Using point-mutated Atox1
      variants, we show that the adduct forms in the absence of conserved residues M10
      or T11 but K60 is essential for heterocomplex formation and Cu transfer.
      Dissection of heterocomplex energetic components reveals a crucial role for K60
      mediated electrostatic interaction.

PMID- 19863065
TI  - One-dimensional assembly of silica nanospheres mediated by block copolymer in
      liquid phase.
AB  - Colloidal silica spheres and their assembly processes are encountered in nature
      and numerous technological applications. We report here a novel and facile method
      to prepare highly anisotropic one-dimensional (1D) arrays of silica nanospheres
      (SNSs) in the liquid phase. Uniform-sized SNSs ca. 15 nm in size assemble into a
      1D chain-like structure in the presence of a commercially available block
      copolymer. The 1D assembly in the liquid phase is evident from Cryo-TEM
      observations and time-dependent turbidity measurement of the suspension. The mode
      of the assembly has been systematically controlled by the concentration of the
      block copolymer, pH of the suspension, and the concentration of a salt added to
      the system. These results suggest the importance of the balance between
      electrostatic repulsion and block copolymer-mediated attractive interaction that
      are operative between particles in the formation of 1D array.

PMID- 19863066
TI  - Comparison of structural behavior of nanocrystals in randomly packed films and
      long-range ordered superlattices by time-resolved small angle X-ray scattering.
AB  - We evaluated the difference between randomly packed NCs (disordered films),
      periodic films, and three-dimensional crystals in terms of their lattice
      structure and interparticle spacing using time-resolved small-angle X-ray
      scattering (SAXS) technique. The work was performed on nanocrystal solids formed
      by 7 nm PbS nanocrystals capped with oleic acid. We have found that interparticle
      spacing in faceted three-dimensional crystals is approximately 25% smaller as
      compared with three-dimensional films formed by solvent evaporation. We showed
      that interparticle spacing in faceted three-dimensional crystals is significantly
      smaller than the length of a fully extended molecule of oleic acid, and hence,
      full interdigitation of molecules from neighboring particle is doubtful. Also we
      demonstrated that postpreparative mild thermal treatment allows further
      manipulation of interparticle spacing.

PMID- 19863067
TI  - Optimization of the matrix solid phase dispersion extraction procedure for the
      analysis of polybrominated diphenyl ethers in human placenta.
AB  - Characterization of prenatal exposure to hazardous chemicals most often relies
      upon the analysis of cord blood. However, human placenta is an appropriate tissue
      alternative with noteworthy advantages. Owing to analytical challenges, reports
      on placental levels of toxic chemicals are limited. The purpose of this study was
      to establish a reliable, cost-effective, and relatively fast and simple method to
      extract polybrominated diphenyl ethers (PBDEs) from human placenta for analysis
      using gas chromatography coupled with mass spectrometry (GC/MS). The matrix solid
      phase dispersion (MSPD) method was optimized for the extraction and analysis of
      43 PBDEs (including BDE209) from human placenta samples. Different sorbents,
      sample conditions, grinding methods, elution solvents, and single and repeated
      extractions were compared for their effects on the extraction efficiency. The
      performance of the optimized method was validated by analyzing spiked placenta
      samples and a standard reference material of fish tissue. Congener specific PBDE
      recovery ranged from 91% to 114% for the spiked samples and 89% to 115% for a
      standard reference material (SRM) of fish tissue. The optimized MSPD procedure
      was compared with two conventional extraction methods. The extraction efficiency
      of MSPD was found to be comparable with that of the traditional Soxhlet method
      and superior to that using a liquid extraction method. Twenty two PBDEs were
      detected in all of the five samples collected in Chicago in 2008. This is the
      first description of PBDEs detected in human placentas in the U.S.

PMID- 19863069
TI  - Nanoclusters of gold on a high-area support: almost uniform nanoclusters imaged
      by scanning transmission electron microscopy.
AB  - Highly dispersed supported gold offers unprecedented catalytic properties.
      Determination of the dependence of the catalytic properties on the gold
      nanocluster size requires the preparation of size-controlled gold nanoclusters on
      support surfaces with a high degree of uniformity. Starting from site-isolated
      mononuclear gold complexes on high-area MgO, we demonstrate the preparation of
      gold clusters consisting of <10 atoms. These samples have been imaged with atomic
      resolution by aberration-corrected scanning transmission electron microscopy. The
      images show that treatment of the supported mononuclear complexes at 318 K in
      flowing helium caused aggregation of the gold into clusters of 2-6 atoms, present
      with unconverted individual site-isolated mononuclear gold species and in the
      absence of any larger nanoparticles. Treatment of the sample at a higher
      temperature (373 K) in flowing helium resulted in the formation of gold clusters
      with diameters of 0.58 +/- 0.15 nm (containing roughly 10 Au atoms), again in the
      absence of larger nanoparticles. Upon exposure of the supported nanoclusters to
      the electron beam, they underwent aggregation to gold clusters approximately 1 nm
      in average diameter, as shown in consecutive STEM images.

PMID- 19863068
TI  - Reactivities of Fe(IV) complexes with oxo, hydroxo, and alkylperoxo ligands: an
      experimental and computational study.
AB  - In a previous paper [Jensen et al. J. Am. Chem. Soc. 2005, 127, 10512], we
      reported the synthesis of the turquoise-colored intermediate [Fe(IV)(beta
      BPMCN)(OO(t)Bu)(OH)](2+) (Tq; BPMCN = N,N'-bis(2-pyridylmethyl)-N,N'-dimethyl
      trans-1,2-diaminocyclohexane). The structure of Tq is unprecedented, as it
      represents the only synthetic example to date of a nonheme Fe(IV) complex with
      both alkylperoxo and hydroxide ligands. Given the significance of similar high
      valent Fe intermediates in the mechanisms of oxygenase enzymes, we have explored
      the reactivity of Tq at -70 degrees C, a temperature at which it is stable, and
      found that it is capable of activating weak X-H bonds (X = C, O) with bond
      dissociation energies < or = approximately 80 kcal/mol. The Fe(IV)-OH unit of Tq,
      and not the alkylperoxo moiety, performs the initial H-atom abstraction. However
      at -45 degrees C, Tq decays at a rate that is independent of substrate identity
      and concentration, forming a species capable of oxidizing substrates with
      stronger C-H bonds. Parallel reactivity studies were also conducted with the
      related oxoiron(IV) complexes [Fe(IV)(beta-BPMCN)(O)(X)](2+) (3-X; X = pyridine
      or nitrile), thereby permitting a direct comparison of the reactivity of Fe(IV)
      centers with oxo and hydroxide ligands. We found that the H-atom abstracting
      ability of the Fe(IV)=O species greatly exceeds that of the Fe(IV)-OH species,
      generally by greater than 100-fold. Examination of the electronic structures of
      Tq and 3-X with density functional theory (DFT) provides a rationale for their
      differing reactivities.

PMID- 19863070
TI  - Noncentrosymmetry in new templated gallium fluorophosphates.
AB  - Two new noncentrosymmetric polar gallium fluorophosphates have been synthesized
      under mild hydrothermal conditions through the use of enantiomorphically pure
      sources of either R-2-methylpiperazine or S-2-methylpiperazine. A centrosymmetric
      analogue was also prepared using a racemic source of the amine. Novel
      [Ga(3)F(PO(4))(4)](n)(4n-) layers, constructed from [Ga(3)O(3)F(PO(4))(4)]
      building units, are observed in all three compounds. The use of racemic 2
      methylpiperazine results in crystallographic disorder of the amines and creation
      of inversion centers, while using a single enantiomer destroys the inversion
      symmetry and orders the amines. Second harmonic generation measurements were
      performed on [(R)-C(5)H(14)N(2)](2)[Ga(3)F(PO(4))(4)] x 5.5 H(2)O and [(S)
      C(5)H(14)N(2)](2)[Ga(3)F(PO(4))(4)] x 4.75 H(2)O, both of which display type 1
      phase-matching capabilities and exhibit activities of approximately 50 x alpha
      SiO(2). The structures of these compounds were determined using single crystal X
      ray diffraction, infrared spectroscopy, and thermal analyses.
      [C(5)H(14)N(2)](2)[Ga(3)F(PO(4))(4)] x 5.25 H(2)O, a = 13.0863(5) A, c =
      9.9023(4) A, trigonal, P-3 (No. 147), Z = 2; [(R)
      C(5)H(14)N(2)](2)[Ga(3)F(PO(4))(4)] x 5.5 H(2)O, a = 13.0887(2) A, c = 29.9439(4)
      A, trigonal, P3(1) (No. 144), Z = 6; [(S)-C(5)H(14)N(2)](2)[Ga(3)F(PO(4))(4)] x
      4.75 H(2)O, a = 13.0871(2) A, c = 29.8350(6) A, trigonal, P3(2) (No. 145), Z = 6.

PMID- 19863071
TI  - Structure determination of a new juvenile hormone from a heteropteran insect.
AB  - The structure of the juvenile hormone (JH) in the suborder Heteroptera, order
      Hemiptera, has been known for a very long time to be different from the JH of
      other orders, but the structure has been a matter of controversy. The structure
      was first elucidated by an unprecedented approach involving the screening of a JH
      molecular library. The novel Heteroptera-specific JH (JHSB(3)) is a new category
      of JH that is featured by the skipped bisepoxide structure.

PMID- 19863072
TI  - Dual signal amplification of glucose oxidase-functionalized nanocomposites as a
      trace label for ultrasensitive simultaneous multiplexed electrochemical detection
      of tumor markers.
AB  - A novel tracer, glucose oxidase-functionalized nanocomposite, was designed to
      label the signal antibodies for ultrasensitive multiplexed measurement of tumor
      markers using a disposable immunosensor array. The immunosensor array was
      constructed by coating layer-by-layer colloidal Prussian blue (PB), gold
      nanoparticles, and capture antibodies on screen-printed carbon electrodes. The
      preparation of glucose oxidase-functionalized nanocomposites and the labeling of
      antibody were performed by one-pot assembly of glucose oxidase and antibody on
      gold nanoparticles attached carbon nanotubes. The PB immobilized on immunosensor
      surface acted as a mediator to catalyze the reduction of H2O2 produced in the
      enzymatic cycle. Both the high-content glucose oxidase and carbon nanotubes in
      the tracer amplified the detectable signal for the sandwich-type immunoassay.
      Using carcinoembryonic antigen and alpha-fetoprotein as model analytes, the
      simultaneous multiplexed immunoassay method using the immunosensor array and the
      designed tracer showed linear ranges of 3 orders of magnitude with the detection
      limits down to 1.4 and 2.2 pg/mL, respectively. The assay results of serum
      samples with the proposed method were in an acceptable agreement with the
      reference values. The dual signal amplification of glucose oxidase-functionalized
      nanocomposites provided a promising ultrasensitive simultaneous multiplexed
      immunoassay approach for clinical applications.

PMID- 19863074
TI  - Facile method to prepare smooth and homogeneous polymer brush surfaces of varied
      brush thickness and grafting density.
AB  - This Article describes a facile method to prepare smooth and homogeneous polymer
      brush surfaces of variable grafting density from a solid surface by combining
      Langmuir-Blodgett (LB) deposition with surface-initiated atom transfer radical
      polymerization (SI-ATRP). This method is successfully demonstrated by the
      preparation of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brush
      surfaces on smooth silicon and quartz substrates. With the custom-synthesized
      inert diluent whose chemical structure, except end-functionality, is the same as
      that of the reactive initiator, smooth and chemically homogeneous mixed
      monolayers of initiators and inert diluents are immobilized on a solid surface by
      LB deposition, allowing the further variation of the grafting density of PNIPAM
      brushes grafted from the initiator monolayers of varied initiator coverage. With
      the optimized molar ratio of deactivator, Cu(II) in the Cu(I)-ligand catalyst
      complex, the brush thickness of PNIPAM brushes at varied grafting density is
      controlled to grow nearly linearly with reaction time while smoothness and
      chemical homogeneity of PNIPAM brushes are achieved. For the demonstrated PNIPAM
      brush surfaces, the thermoresponsive characteristics of PNIPAM brushes are also
      verified. This combined LB-ATRP method can be applied to graft a variety of
      polymer brushes, including polyelectrolytes and block copolymers, from different
      solid substrates.

PMID- 19863073
TI  - Total syntheses of all stereoisomers of phenatic acid B.
AB  - The total syntheses of all stereoisomers of phenatic acid B and determination of
      their absolute configuration are described. The synthetic strategy is based on an
      efficient combination of the Sharpless asymmetric dihydroxylation, the Johnson
      Claisen rearrangement, and hydroboration-oxidation. It involves 11-12 steps and
      overall yield of 5-8%.

PMID- 19863075
TI  - Construction of multiring frameworks by metal-free cascade reactions of stable
      isochromenylium tetrafluoroborate.
AB  - Efficient methodologies for constructing several multiring frameworks have been
      developed utilizing the cascade reactions of air-stable isochromenylium
      tetrafluoroborates with olefins. Successive additions of two equivalents of
      styrene-type olefins to isochromenylium tetrafluoroborate (ICTB) 1 have been
      observed and their mechanisms were proposed and discussed. Intramolecular capture
      of the early stage cationic intermediates by predevised heteroatoms or Friedel
      Crafts donors provided two different types of bridged-ring systems.

PMID- 19863076
TI  - Synthetic routes to meso-patterned porphyrins.
AB  - Synthetic meso-substituted porphyrins offer significant attractions compared with
      naturally occurring beta-substituted porphyrins. The attractions include the
      rectilinear arrangement of the four meso substituents and potential synthetic
      amenability from pyrrole and simple acyl reactants, thereby avoiding the
      cumbersome syntheses of beta-substituted pyrroles. In practice, however, the
      classical methods for the synthesis of meso-substituted porphyrins were
      characterized by high-temperature reactions, limited scope of substituents, and
      statistical mixtures accompanied by laborious chromatography if porphyrins
      bearing two different types of substituents were sought. Such methods left
      unrealized the tremendous utility of meso-substituted porphyrins across the
      enormously broad field of porphyrin science, which touches pure chemistry;
      energy, life and materials sciences; and medicine. This Account surveys a set of
      strategies, developed over a generation, that provide rational access to
      porphyrins bearing up to four distinct meso substituents. A "2 + 2" route employs
      a dipyrromethane-1,9-dicarbinol and a dipyrromethane (bearing ABC- and D
      substituents, respectively) in a two-step, one-flask process of acid-catalyzed
      condensation followed by oxidation at room temperature to form the free base
      "ABCD-porphyrin." A "bilane" route relies on the acid-catalyzed reaction of a 1
      acyldipyrromethane (CD substituents) and a 9-bromodipyrromethane-1-carbinol (AB
      substituents) to form the corresponding 19-acyl-1-bromobilane. Reaction of the
      latter compound in the presence of MgBr(2), 1,8-diazabicyclo[5.4.0]undec-7-ene
      (DBU), and toluene at reflux exposed to air affords the corresponding
      magnesium(II) porphyrin. The two routes are complementary, both in scope and in
      implementation. A suite of methods also affords trans-A(2)B(2)-porphyrins by
      reaction of a dipyrromethane and an aldehyde, self-condensation of a
      dipyrromethane-1-carbinol, or self-condensation of a 1-acyldipyrromethane. These
      new routes are also useful for preparing sparsely substituted porphyrins, which
      bear fewer than four meso substituents (e.g., trans-AB-porphyrins, A-porphyrins).
      Because of their compact size and the ability to incorporate hydrophilic or
      amphipathic groups, such molecules are ideal for biological applications. The
      success of these new synthetic strategies has relied on a number of advances
      including (1) the development of simple yet efficient routes to dipyrromethanes,
      acyldipyrromethanes, and dipyrromethane-carbinols, (2) the identification of acid
      catalysts and reaction conditions for condensations of pyrromethane species
      without accompanying acidolysis (which underlies scrambling and formation of a
      mixture of porphyrin products), (3) the development of analytical methods to
      rapidly screen for scrambling and to characterize the distribution of
      oligopyrromethanes and macrocycles, (4) selection and refinement of synthetic
      methods to increase yields and to limit or avoid use of chromatography, thereby
      achieving scalability to multigram levels, and (5) exploitation of discoveries
      concerning the fundamental chemistry of pyrrolic species. With these
      developments, the prior era of porphyrin synthesis has been supplanted with
      rational routes that proceed under very mild conditions and afford a single
      porphyrin bearing up to four distinct meso substituents. The meso substituents
      encompass a very wide range of molecular complexity. The resulting porphyrins can
      serve as building blocks in the construction of model systems, as components of
      molecular materials, and as surrogates for naturally occurring tetrapyrrole
      macrocycles.

PMID- 19863077
TI  - TSPO targeted dendrimer imaging agent: synthesis, characterization, and cellular
      internalization.
AB  - While it has become common practice for dendrimers to deliver imaging and
      therapeutic agents, there are few reported examples of cellular internalization
      of dendrimers. Moreover, targeting of dendrimers to the mitochondria in cells has
      not yet been reported. Previously, we have delivered small molecule imaging
      agents into glioma and breast cancer cells by targeting the translocator protein
      (TSPO; formerly known as the peripheral benzodiazepine receptor or PBR) with a
      family of high-affinity conjugable ligands. The 18 kDa multimeric TSPO is
      expressed in steroid-producing cells, primarily on the outer mitochondrial
      membrane. This protein is a prime candidate for molecular targeting because
      tumors and other disease-related cells contain high densities of TSPO. Here, we
      present the synthesis, characterization, and cellular internalization into C6 rat
      glioma cells of a TSPO targeted dendrimer imaging agent.

PMID- 19863078
TI  - Snake venomics of the Central American rattlesnake Crotalus simus and the South
      American Crotalus durissus complex points to neurotoxicity as an adaptive
      paedomorphic trend along Crotalus dispersal in South America.
AB  - We report a comparative venomic and antivenomic characterization of the venoms of
      newborn and adult specimens of the Central American rattlesnake, Crotalus simus,
      and of the subspecies cumanensis, durissus, ruruima, and terrificus of South
      American Crotalus durissus. Neonate and adult C. simus share about 50% of their
      venom proteome. The venom proteome of 6-week-old C. simus is predominantly made
      of the neurotoxic heterodimeric phospholipase A(2) (PLA(2) crotoxin) (55.9%) and
      serine proteinases (36%), whereas snake venom Zn(2+)-metalloproteinases (SVMPs),
      exclusively of class PIII, represent only 2% of the total venom proteins. In
      marked contrast, venom from adult C. simus comprises toxins from 7 protein
      families. A large proportion (71.7%) of these toxins are SVMPs, two-thirds of
      which belong to the PIII class. These toxin profiles correlate well with the
      overall biochemical and pharmacological features of venoms from adult
      (hemorrhagic) and newborn (neurotoxic) C. simus specimens. The venoms of the
      South American Crotalus subspecies belong to one of two distinct phenotypes. C.
      d. cumanensis exhibits high levels of SVMPs and low lethal potency (LD(50)),
      whereas C. d. subspecies terrificus, ruruima, and durissus have low SVMP activity
      and high neurotoxicity to mice. Their overall toxin compositions explain the
      outcome of envenomation by these species. Further, in all C. simus and C.
      durissus venoms, the concentration of neurotoxins (crotoxin and crotamine) is
      directly related with lethal activity, whereas lethality and metalloproteinase
      activity show an inverse relationship. The similar venom toxin profiles of
      newborn C. simus and adult C. durissus terrificus, ruruima, and durissus
      subspecies strongly suggests that the South American taxa have retained juvenile
      venom characteristics in the adult form (paedomorphism) along their North-South
      stepping-stone dispersal. The driving force behind paedomorphism is often
      competition or predation pressure. The increased concentration of the neurotoxins
      crotoxin and crotamine in South American rattlesnake venoms strongly argues that
      the gain of neurotoxicity and lethal venom activities to mammals may have
      represented the key axis along which overall venom toxicity has evolved during
      Crotalus durissus invasion of South America. The paedomorphic trend is supported
      by a decreasing LNC (lethal neurotoxicity coefficient, defined as the ratio
      between the average LD(50) of the venom and the crotoxin + crotamine
      concentration) along the North-South axis, coincident with the evolutionary
      dispersal pattern of the Neotropical rattlesnakes. The indistinguisable
      immunoreactivity patterns of Costa Rican and Venezuelan polyvalent antivenoms
      toward C. simus and C. durissus venoms strongly suggest the possibility of using
      these antivenoms indistinctly for the management of snakebites by adult C. simus
      and by certain C. d. cumanensis populations exhibiting a hemorrhagic venom
      phenotype. The antivenomic results also explain why the antivenoms effectively
      neutralize the hemorrhagic activity of adult C. simus venoms but does not protect
      against adult C. durissus sp. and newborn C. simus envenomations. The
      identification of evolutionary trends among tropical Crotalus, as reported here,
      may have an impact in defining the mixture of venoms for immunization to produce
      an effective pan-American anti-Crotalus antivenom.

PMID- 19863080
TI  - Ambient mass spectrometric detection of organometallic compounds using direct
      analysis in real time.
AB  - The present work describes the mass spectrometric detection of organometallic
      compounds following their atmospheric pressure ionization using a commercial
      direct analysis in real time (DART) ion source. Several organometallic compounds
      of As, Fe, Hg, Pb, Se, and Sn were examined, and their corresponding mass spectra
      as well as induced fragmentation patterns were recorded. Gas phase sampling of
      the pure organometallic compounds or their solutions prepared in toluene
      generated temporally stable signals. For the majority of the compounds, the
      molecular ion or protonated molecule was detected; noticeable exceptions are the
      tetra-substituted compounds for which their less-substituted species dominated.
      The organometallic species were used as model compounds for a systematic
      investigation of the impact of operating parameters of the DART source, including
      gas temperature and electrode voltages. In general, results have shown that
      powering the electrodes designed to remove ions from the DART gas stream results
      in a reduction in signal intensity for most of the compounds investigated,
      suggesting that charged species from the plasma play an important role in the
      ionization process of the test analytes.

PMID- 19863079
TI  - Structural, thermodynamic, and kinetic effects of a phosphomimetic mutation in
      dynein light chain LC8.
AB  - Dynein light chain LC8 is a small, dimeric, very highly conserved globular
      protein first identified as an integral part of the dynein and myosin molecular
      motors but now recognized as a dimerization hub with wider significance.
      Phosphorylation at Ser88 is thought to be involved in regulating LC8 in the
      apoptotic pathway. The phosphomimetic Ser88Glu mutation weakens dimerization of
      LC8 and thus its overall ligand-binding affinity, because only the dimer binds
      ligands. The 1.9 A resolution crystal structure of dimeric LC8(S88E) bound to a
      fragment of the ligand Swallow (Swa) presented here shows that the tertiary
      structure is identical to that of wild-type LC8/Swa, with Glu88 well accommodated
      sterically at the dimer interface. NMR longitudinal magnetization exchange
      spectroscopy reveals remarkably slow association kinetics (k(on) approximately 1
      s(-1) mM(-1)) in the monomer-dimer equilibrium of both wild-type LC8 and
      LC8(S88E), possibly due to the strand-swapped architecture of the dimer. The
      Ser88Glu mutation raises the dimer dissociation constant (K(D)) through a
      combination of a higher k(off) and lower k(on). Using a minimal model of
      titration linked to dimerization, we dissect the thermodynamics of dimerization
      of wild-type LC8 and LC8(S88E) in their various protonation states. When both
      Glu88 residues are protonated, the LC8(S88E) dimer is nearly as stable as the
      wild-type dimer, but deprotonation of one Glu88 residue raises K(D) by a factor
      of 400. We infer that phosphorylation of one subunit of wild-type LC8 raises K(D)
      by at least as much to prevent dimerization of LC8 at physiological
      concentrations. Some LC8 binding partners may bind tightly enough to promote
      dimerization even when one subunit is phosphorylated; thus linkage between
      phosphorylation and dimerization provides a mechanism for differential regulation
      of binding of LC8 to its diverse partners.

PMID- 19863081
TI  - Anomalous dissipation in single-walled carbon nanotube resonators.
AB  - We observe a new anomalous and transient process of intrinsic dissipation in
      simulations of the ring-down of flexural modes in single-walled carbon nanotube
      (CNT) resonators. The effect is pronounced, causing the quality factor of the
      mode to be reduced by more that 95% for tens of picoseconds. The anomalous
      dissipation depends on the CNT temperature and the energy in the mode, and
      remarkably increasing the excitation energy in the resonator causes it to decay
      to zero faster. By tracking the cascade of energy as it dissipates we identify
      "gateway" modes that provide important channels for dissipation. The processes we
      observe show that an athermal phonon population accompanying dissipation can
      strongly influence the quality factor in nanoelectromechanical devices.

PMID- 19863082
TI  - Hydrogen-bond-induced microstructural transition of ionic micelles in the
      presence of neutral naphthols: pH dependent morphology and location of surface
      activity.
AB  - The effect of naphthols and methoxynaphthalenes on the microstructure transition
      of cetyltrimethylammonium bromide (CTAB) micelles is studied. Although the
      surface activities of these two types of organic dopants are strong,
      methoxynaphthalenes failed to promote spherical to worm-like micellar transition
      and to impart viscoelasticity to the aqueous CTAB solution, presumably due to
      their inability to form unique H-bonds with interfacial water. The micropolarity
      of OH sites of micelle-embedded naphthols is measured by observing the pK(a)
      shift at the micellar surface relative to bulk water. On the basis of
      spectroscopic and other data, the microstructures formed by both classes of
      dopants at the micellar surface are predicted. On the basis of hydroxyaromatic
      dopants, a simple and effective route to design pH-responsive viscoelastic worm
      like micelles and the vesicles of single tail cationic surfactant (CTAB) is
      reported. Results are confirmed by observing cryogenic transmission electron
      microscopy (cryo-TEM) images.

PMID- 19863083
TI  - The lecanindoles, nonsteroidal progestins from the terrestrial fungus
      Verticillium lecanii 6144.
AB  - Four new indolosesquiterpenes, lecanindoles A-D (1-4), were isolated from
      fermentations of the terrestrial fungus Verticillium lecanii 6144. The structures
      of compounds 1-4 were elucidated from analysis of spectroscopic data. Compound 2
      was reduced to give 4 and its isomer 5. Compound 4 was found to be a potent and
      selective progesterone receptor agonist with an EC50 of 1.1 +/- 0.4 nM in a cell
      based luciferase reporter assay.

PMID- 19863084
TI  - Comparative flavan-3-ol profile and antioxidant capacity of roasted peanut,
      hazelnut, and almond skins.
AB  - In the present study, the flavan-3-ol composition and antioxidant capacity of
      roasted skins obtained from the industrial processing of three commonly consumed
      tree nuts (i.e., peanuts, hazelnuts, and almonds), as well as fractions
      containing low and high molecular weight (LMW and HMW) flavan-3-ols, were studied
      with the aim of assessing their potential as a source of flavonoids. Roasted
      peanut and hazelnut skins presented similar total phenolic contents, much higher
      than that of almond skins, but their flavan-3-ol profiles, as determined by LC
      ESI-MS and MALDI-TOF MS, differed considerably. Peanut skins were low in
      monomeric flavan-3-ols (19%) in comparison to hazelnut (90%) and almond (89%)
      skins. On the other hand, polymeric flavan-3-ols in peanut and almond skins
      occurred as both A- and B-type proanthocyanidins, but in peanuts the A forms (up
      to DP12) were predominant, whereas in almonds the B forms (up to DP8) were more
      abundant. In contrast, hazelnuts were mainly constituted by B-type
      proanthocyanidins (up to DP9). The antioxidant capacity as determined by various
      methods (i.e., total antioxidant capacity, ORAC, DPPH test, and reducing power)
      was higher for whole extracts from roasted hazelnut and peanut skins than for
      almond skins; however, the antioxidant capacities of the HMW fraction of the
      three types of nut skins were equivalent despite their different compositions and
      DPs. Nevertheless, the large variation in flavan-3-ol concentration, structural
      composition, type of interflavan linkage, and DP found among the three types of
      nut skins suggests large difference in their expected in vivo biological
      activities.

PMID- 19863086
TI  - Spin polarized conductance in hybrid graphene nanoribbons using 5-7 defects.
AB  - We present a class of intramolecular graphene heterojunctions and use first
      principles density functional calculations to describe their electronic,
      magnetic, and transport properties. The hybrid graphene and hybrid graphene
      nanoribbons have both armchair and zigzag features that are separated by an
      interface made up of pentagonal and heptagonal carbon rings. Contrary to
      conventional graphene sheets, the computed electronic density of states indicates
      that all hybrid graphene and nanoribbon systems are metallic. Hybrid nanoribbons
      are found to exhibit a remarkable width-dependent magnetic behavior and behave as
      spin polarized conductors.

PMID- 19863085
TI  - Effect of a purification step and the type of internal standard used on fatty
      acid determination of grass and maize silages.
AB  - The fatty acid (FA) analysis of grass and maize silages was studied by
      application of a direct transesterification method (DT) followed by purification
      by solid-phase extraction (SPE). The choice of the internal standard (IS) for
      quantification of FA by gas-liquid chromatography (GLC) was also studied. The
      acidic DT method applied to grass silage samples produced a high amount of non
      fatty acid methyl ester compounds (non-FAME) compared with those formed in maize
      silages. The application of the SPE cleanup step reduced significantly the amount
      of non-FAME compounds in both samples. Five FAs were tested as IS; among them, 3
      were naturally present in all silages, however their use as IS did not affect
      quantification of total FA composition. Nevertheless, some minor FAs present in
      silages were significantly affected by the IS used. Additionally, application of
      corrections to the GLC peak areas did not significantly influence quantification
      of total FA composition of silages.

PMID- 19863087
TI  - Photoluminescent diamond nanoparticles for cell labeling: study of the uptake
      mechanism in mammalian cells.
AB  - Diamond nanoparticles (nanodiamonds) have been recently proposed as new labels
      for cellular imaging. For small nanodiamonds (size <40 nm), resonant laser
      scattering and Raman scattering cross sections are too small to allow single
      nanoparticle observation. Nanodiamonds can, however, be rendered photoluminescent
      with a perfect photostability at room temperature. Such a remarkable property
      allows easier single-particle tracking over long time scales. In this work, we
      use photoluminescent nanodiamonds of size <50 nm for intracellular labeling and
      investigate the mechanism of their uptake by living cells. By blocking
      selectively different uptake processes, we show that nanodiamonds enter cells
      mainly by endocytosis, and converging data indicate that it is clathrin-mediated.
      We also examine nanodiamond intracellular localization in endocytic vesicles
      using immunofluorescence and transmission electron microscopy. We find a high
      degree of colocalization between vesicles and the biggest nanoparticles or
      aggregates, while the smallest particles appear free in the cytosol. Our results
      pave the way for the use of photoluminescent nanodiamonds in targeted
      intracellular labeling or biomolecule delivery.

PMID- 19863089
TI  - Synthesis, structure, and photophysical characterization of blue-green
      luminescent zinc complexes containing 2-iminophenanthropyrrolyl ligands.
AB  - New 2-iminophenanthro[9,10-c]pyrrole ligand precursors containing phenyl or 2,6
      diisopropylphenyl groups at the imine nitrogen substituent, 2
      arylformiminophenanthro[9,10-c]pyrroles (aryl = phenyl IIa, 2,6-diisopropylphenyl
      IIb) were synthesized and deprotonated in situ with NaH, originating solutions of
      the corresponding sodium salts (IVa, IVb). The reaction of these salts with zinc
      chloride gave the homoleptic bis-ligand Zn(II) complexes [Zn(kappa(2)N,N'-2
      arylformiminophenanthro[9,10-c]pyrrolyl)(2)] (aryl = phenyl 2a, 2,6
      diisopropylphenyl 2b). The new ligand precursors and complexes were characterized
      by NMR, elemental analysis, UV/vis spectroscopy, and X-ray crystallography, when
      possible. The photophysical characterization was carried out using steady-state
      and picosecond time-resolved luminescence techniques in solution. The influence
      of the pi-extended conjugation of the condensed phenanthro group on the
      deprotonated iminopyrrolyl ligands coordinated to Zn(2+) greatly enhances
      fluorescence quantum yields of the complexes (2a, 2b) in relation to those of
      their ligand precursors (IIa, IIb). Complex 2a shows emission in the green
      spectral region (lambda(max) = 494 nm), presenting the highest fluorescence
      quantum yield (phi(f) = 8.8%). In the case of the complex 2b (phi(f) = 3.9%), the
      bulkiness of the 2,6-diisopropyl substituents of the arylimino group highly
      restricts the aryl ring rotation toward coplanarity with the ligand framework,
      inducing a shift in the emission to the blue region (lambda(max) = 459 nm). The
      values of the radiative (k(f)) and radiationless rate constants (k(nr)) show that
      the fluorescence quantum yield enhancement in the complexes results from a 50
      fold increase in k(f) values, indicating much more allowed pi-pi* transitions in
      complexes 2a and 2b than those occurring in the ligand precursors IIa and IIb,
      with an essentially n-pi* character. These assignments were confirmed by density
      functional theory (DFT) and time-dependent DFT (TD-DFT) molecular orbital
      calculations. Simple 2-aryliminopyrrole ligand precursors (Ia, Ib) and their
      Zn(II) complexes (1a, 1b) were also prepared to compare their photophysical
      properties with those of the corresponding 2-aryliminophenanthro[9,10-c]pyrrolyl
      compounds.

PMID- 19863088
TI  - Label-free Raman spectral imaging of intracellular delivery and degradation of
      polymeric nanoparticle systems.
AB  - Novel optical imaging methods, such as Raman microspectroscopy, have been gaining
      recognition in their ability to obtain noninvasively the distribution of
      biochemical components of a sample. Raman spectroscopy in combination with
      optical microscopy provides a label-free method to assess and image cellular
      processes, without the use of extrinsic fluorescent dyes. The submicrometer
      resolution of the confocal Raman instrumentation allows us to image cellular
      organelles on the scale of conventional microscopy. We used the technique to
      monitor subcellular degradation patterns of two biodegradable nanocarrier systems
      poly(epsilon-caprolactone) (PCL) and poly(lactic-co-glycolic acid) (PLGA). Our
      results suggest that both drug-delivery systems eventually are incorporated into
      Golgi-associated vesicles of late endosomes. These processes were monitored via
      the decrease of the molecule-characteristic peaks of PCL and PLGA. As the
      catabolic pathways proceed, shifts and variations in peak intensities and
      intensity ratios in the rendered Raman spectra unequivocally delineate their
      degradation patterns.

PMID- 19863090
TI  - Radiative decay of singlet excitons and carrier-fusion-induced
      electroluminescence enhancement of polymer light-emitting diodes.
AB  - During the radiative decay of singlet excitons in polymer light-emitting diodes
      (PLEDs), the newly developed molecule dynamics not only describes the evolution
      of the lattice distortion of the polymer chain but also illustrates the time
      dependent electron transitions and electron populations in detail. Furthermore,
      based on this method, it is revealed that the nonemissive triplet excitons in
      PLEDs become emissive through the fusion of injected positive polarons. The
      obtained maximum quantum efficiency is consistent with recent experimental
      results.

PMID- 19863091
TI  - Local order, energy, and mobility of water molecules in the hydration shell of
      small peptides.
AB  - The extent to which the presence of a biomolecular solute modifies the local
      energetics of water molecules, as measured by the tagged molecule potential
      energy (TPE), is examined using molecular dynamics simulations of the beta
      hairpin of 2GB1 and the alpha-helix of deca-alanine in water. The CHARMM22 force
      field, in conjunction with the TIP3P solvent water model, is used for the
      peptides, with simulations of TIP3P and SPC/E water used as benchmarks for the
      behavior of bulk solvent. TIP3P water is shown to have significantly lower local
      tetrahedral order and higher binding energy than SPC/E at the same state point.
      The TIP3P and SPC/E water models show very similar dynamical correlations in the
      TPE fluctuations on frequency scales greater than 0.1 cm(-1). In addition, the
      two models show the same linear correlation between mean tetrahedral order and
      binding energy, suggesting that the relationship between choice of water models
      and simulated hydration behavior may involve a complex interplay of static and
      dynamic factors. The introduction of a peptide in water modifies the local TPE of
      water molecules as a function of distance from the biomolecular interface. There
      is an oscillatory variation in the TPE with distance from the peptide for water
      molecules lying outside a 3 A radius and extending to at least 10 A. These
      variations are of the order of 2-5% of the bulk TPE value and are anticorrelated
      with variations in local tetrahedral order in terms of locations of maxima and
      minima, which may be understood in terms of the relative contribution of van der
      Waals and Coulombic contributions to the TPE. The distance-dependent variations
      in local order and energetics are essentially the same for the beta-hairpin of
      2GB1 as well as deca-alanine. Within a radius of 3 A, the perturbation of the
      solvent structure is very significant with local TPEs that are 10-15% lower than
      the bulk value. The chemical identity of side-chain residues and the secondary
      structure play an important role in determining residue-dependent variations in
      the TPEs. The variation in the residue-dependent tagged molecule potential
      energies is of the order of 3-5%, while the local residence times vary by a
      factor of approximately 5. The correlation of the local residence times with the
      local energetics within the innermost hydration layer is weak, though charged
      residues typically have low binding energies and large residence times.

PMID- 19863092
TI  - Density-based clustering of small peptide conformations sampled from a molecular
      dynamics simulation.
AB  - This study describes the application of a density-based algorithm to clustering
      small peptide conformations after a molecular dynamics simulation. We propose a
      clustering method for small peptide conformations that enables adjacent clusters
      to be separated more clearly on the basis of neighbor density. Neighbor density
      means the number of neighboring conformations, so if a conformation has too few
      neighboring conformations, then it is considered as noise or an outlier and is
      excluded from the list of cluster members. With this approach, we can easily
      identify clusters in which the members are densely crowded in the conformational
      space, and we can safely avoid misclustering individual clusters linked by noise
      or outliers. Consideration of neighbor density significantly improves the
      efficiency of clustering of small peptide conformations sampled from molecular
      dynamics simulations and can be used for predicting peptide structures.

PMID- 19863094
TI  - BF3-H2O catalyzed hydroxyalkylation of aromatics with aromatic aldehydes and
      dicarboxaldehydes: efficient synthesis of triarylmethanes,
      diarylmethylbenzaldehydes, and anthracene derivatives.
AB  - BF(3)-monohydrate is found to be an efficient and strong acid catalyst as well as
      an effective protosolvating medium suitable for the hydroxyalkylation of arenes
      with aromatic aldehydes. This reaction has been extended to aromatic dialdehydes,
      such as terephthalic dicarboxaldehyde and isoterephthalic dicarboxaldehyde, for
      the efficient synthesis of diarylmethylbenzaldehydes, which are useful synthons
      for various organic transformations. Further, successful one step convergent
      synthesis of various synthetically useful anthracene derivatives from
      phthalaldehyde was also achieved. BF(3)-H(2)O is less expensive and acts as an
      efficient substitute for nonoxidizing strong protic acids/superacids.

PMID- 19863095
TI  - Wavelength-selective photoactivatable protecting groups for thiols.
AB  - We developed and characterized efficient, remarkably water-soluble photolabile
      protecting groups for thiols based on 2-nitrobenzyl and (coumarin-4-yl)methyl
      chromophores, among them two new ones. The protecting groups allow, due to their
      different absorption maxima, wavelength-selective photocleavage of binary
      mixtures of cysteine derivatives protected at the thiol function with various
      photolabile protecting groups by irradiation with light. The concept was also
      functional with the two different S-protected cysteine residues in derivatives of
      the model peptide resact. Selective photolysis could be achieved for the peptides
      Ac(0)-Cys(1)(BCMACMOC),Cys(8)(7,8BCMCMOC)-resact and Ac(0)
      Cys(1)(C4MNB),Cys(8)(BCMACMOC)-resact by irradiation with light of > or = 402 nm
      or > or = 436 nm wavelength, respectively, followed by irradiation at lambda > or
      = 325 nm.

PMID- 19863096
TI  - Predictions of the fluorine NMR chemical shifts of perfluorinated carboxylic
      acids, CnF(2n+1)COOH (n = 6-8).
AB  - Perfluorinated carboxylic acids (PFCAs) are a class of persistent environmental
      pollutants. Commercially available PFCAs are mixtures of linear and branched
      isomers, possibly with impurities. Different isomers have different physical and
      chemical properties and toxicities. However, little is known about the properties
      and the finer details of the structures of the individual branched isomers. Full
      geometry optimizations for the linear n-alkane (C(6)-C(27)) PFCAs indicated that
      all have helical structures. The helical angle increases slightly with increasing
      chain length, from 16.3 degrees in C(6)F(13)COOH to 17.0 degrees in
      C(27)F(55)COOH. This study predicts (19)F NMR parameters for 69 linear and
      branched isomers of the perfluoro carboxylic acids C(6)F(13)COOH, C(7)F(15)COOH,
      and C(8)F(17)COOH. B3LYP-GIAO/6-31++G(d,p)//B3LYP/6-31G(d,p) was used for the NMR
      calculations with analysis of the chemical shifts by the natural bond orbital
      method. The predictions of the (19)F chemical shifts revealed the differences
      among the CF(3), CF(2), and CF groups. In general, the absolute values for the
      chemical shifts for the CF(3) group are smaller than 90 ppm, for the CF larger
      than 160 ppm, and for the CF(2) between 110 and 130 ppm. The chemical shifts of
      the branched isomers are smaller in magnitude than the linear ones. The decrease
      is correlated with the steric hindrance of the CF(3) groups, the more hindered
      the CF(3), the greater the decrease in the (19)F chemical shifts. The predicted
      (19)F chemical shifts are similar to those for analogous perfluoro compounds with
      other terminal functional groups such as -SO(3)H or -SO(3)NH(2)CH(2)CH(3).

PMID- 19863097
TI  - Efficient synthesis of naphtho[1,2-e][1,3]oxazine derivatives via a
      chemoselective reaction with the aid of low-valent titanium reagent.
AB  - A series of new naphtho[1,2-e][1,3]oxazine derivatives such as trans-1,3-diaryl
      1H-naphtho[1,2-e][1,3]oxazine-2(3H)-carbonyl chloride, 1-aryl-2-benzyl-1,2-
      dihydronaphtho[1,2-e][1,3]oxazine-3-one, and trans-1,3-diaryl-1H-naphtho[1,2-e]
      [1,3]oxazine-2(3H)-carbaldehyde were selectively synthesized via a chemoselective
      reaction of 1,3-diaryl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines and triphosgene
      or triethyl orthoformate, respectively, induced by different low-valent titanium
      systems. This method has the advantages of short reaction time (15 min),
      convenient manipulation, and high chemoselectivity.

PMID- 19863098
TI  - Structural phase transitions and superconductivity in Fe(1+delta)Se0.57Te0.43 at
      ambient and elevated pressures.
AB  - The ternary iron chalcogenide, Fe(1.03)Se(0.57)Te(0.43) is a member of the
      recently discovered family of Fe-based superconductors with an ambient pressure
      T(c) of 13.9 K and a simple structure comprising layers of edge-sharing distorted
      Fe(Se/Te)(4) tetrahedra separated by a van der Waals gap. Here we study the
      relationship between its structural and electronic responses to the application
      of pressure. T(c) depends sensitively on applied pressure attaining a broad
      maximum of 23.3 K at approximately 3 GPa. Further compression to 12 GPa leads to
      a metallic but nonsuperconducting ground state. High-resolution synchrotron X-ray
      diffraction shows that the superconducting phase is metrically orthorhombic at
      ambient pressure but pressurization to approximately 3 GPa leads to a structural
      transformation to a more distorted structure with monoclinic symmetry. The exact
      coincidence of the crystal symmetry crossover pressure with that at which T(c) is
      maximum reveals an intimate link between crystal and electronic structures of the
      iron chalcogenide superconductors.

PMID- 19863099
TI  - Voltammetrically controlled electron transfer reactions from alkanethiol modified
      gold electrode surfaces to low molecular weight molecules deposited within lipid
      (lecithin) bilayers.
AB  - A procedure was developed for initiating electron transfer from a gold electrode
      to a low molecular weight electron acceptor present inside supported lipid
      (lecithin) bilayers, followed by further electron transfer to an electron
      acceptor present in an aqueous solution. The electron acceptors present in the
      lecithin bilayers and aqueous phase were 7,7,8,8-tetracyanoquinodimethane (TCNQ)
      and [Fe(III)(CN)(6)](3-), respectively. A polished planar gold disk electrode was
      first coated via self-assembly procedures with an alkanethiol monolayer. A
      phospholipid layer consisting of multiple bilayers of lecithin containing TCNQ
      was subsequently deposited onto the alkanethiol monolayer. The
      Au/alkanethiol/lecithin-TCNQ electrode was placed in an aqueous solution
      containing various amounts of [Fe(III)(CN)(6)](3-) and [Fe(II)(CN)(6)](4-), with
      0.5 M KCl as the supporting electrolyte. In the absence of TCNQ inside the
      alkanethiol/lecithin layers, only a small background current was observed. When
      TCNQ was included in the alkanethiol/lecithin layers, the voltammetry showed
      features typical of a catalytic process, due to the TCNQ being reduced to TCNQ(
      *) within the lecithin bilayers and then undergoing oxidation back to TCNQ via
      interaction with [Fe(III)(CN)(6)](3-) at the lecithin-aqueous solution interface.
      The procedures for preparing the alkanethiol/lecithin-TCNQ coatings were
      optimized in order to obtain the most reproducible voltammetric response.
      Experiments were also performed using tetrathiafulvalene (TTF) as an electron
      donor in the lipid bilayer phase.

PMID- 19863100
TI  - One-pot, pseudo four-component synthesis of a spiro[diindeno[1,2-b:2',1'
      e]pyridine-11,3'-indoline]-trione library.
AB  - A one-pot, pseudo four-component method for the efficient and simple synthesis of
      spiro[diindeno[1,2-b:2',1'-e]pyridine-11,3'-indoline]-2',10,12-trione derivatives
      in refluxing acetonitrile is reported. The features of this procedure are mild
      reaction conditions, high yields of products, and operational simplicity.

PMID- 19863101
TI  - Asterolaurins A-F, xenicane diterpenoids from the Taiwanese soft coral
      Asterospicularia laurae.
AB  - Six new xenicane-type diterpenoids, designated as asterolaurins A-F (1-6), have
      been isolated from the organic extract of the soft coral Asterospicularia laurae,
      collected in southern Taiwan. Compounds 1-4 possess a xenicin skeleton with a 2
      oxabicyclo[7.4.0]tridecane ring system, while 5 and 6 are xeniolide A-type
      compounds. The structures of the new secondary metabolites, including their
      configurations, were established on the basis of an extensive spectroscopic
      analysis, including 1D and 2D NMR (1H-1H COSY, HMQC, HMBC, and NOESY), and by
      comparison of their NMR data with those of the related compounds. The structure
      of asterolaurin A (1) was confirmed by X-ray diffraction analysis, and its
      absolute configuration was determined using the modified Mosher's method.
      Asterolaurin A (1) exhibited moderate cytotoxicity against HepG2 cells with an
      IC50 of 8.9 microM, while asterolaurin D (4) showed potent inhibition of elastase
      release and superoxide anion generation in vitro.

PMID- 19863102
TI  - Synthesis of PbS nanorods and other ionic nanocrystals of complex morphology by
      sequential cation exchange reactions.
AB  - We show that nanocrystals (NCs) with well-established synthetic protocols for
      high shape and size monodispersity can be used as templates to independently
      control the NC composition through successive cation exchange reactions. Chemical
      transformations like cation exchange reactions overcome a limitation in
      traditional colloidal synthesis, where the NC shape often reflects the inherent
      symmetry of the underlying lattice. Specifically we show that full or partial
      interconversion between wurtzite CdS, chalcocite Cu(2)S, and rock salt PbS NCs
      can occur while preserving anisotropic shapes unique to the as-synthesized
      materials. The exchange reactions are driven by disparate solubilites between the
      two cations by using ligands that preferentially coordinate to either monovalent
      or divalent transition metals. Starting with CdS, highly anisotropic PbS nanorods
      are created, which serve as an important material for studying strong two
      dimensional quantum confinement, as well as for optoelectronic applications. In
      NC heterostructures containing segments of different materials, the exchange
      reaction can be made highly selective for just one of the components of the
      heterostructure. Thus, through precise control over ion insertion and removal, we
      can obtain interesting CdS|PbS heterostructure nanorods, where the spatial
      arrangement of materials is controlled through an intermediate exchange reaction.

PMID- 19863103
TI  - Bromodecarboxylation of quinoline salicylic acids: increasing the diversity of
      accessible substituted quinolines.
AB  - Quinoline salicylic acids underwent bromodecarboxylation at room temperature upon
      treatment with N-bromosuccinimide. A wide variety of functional groups was
      tolerated. Several one-pot transformations were also carried out, allowing the
      preparation of diverse 4-substituted quinolines.

PMID- 19863104
TI  - Selective lithiation and phosphane-functionalization of [(eta(7)-C7H7)Ti(eta(5)
      C5H5)] (troticene) and its use for the preparation of early-late heterobimetallic
      complexes.
AB  - The cycloheptatrienyl-cyclopentadienyl sandwich complex [(eta(7)
      C(7)H(7))Ti(eta(5)-C(5)H(5))] (troticene) can be dilithiated (once at each ring)
      or selectively monolithiated, either at the seven- or five-membered ring,
      depending on the reaction conditions. Treatment of the resulting lithiotroticenes
      with ClPPh(2) afforded the corresponding troticenyl-phosphanes [(eta(7)
      C(7)H(6)PPh(2))Ti(eta(5)-C(5)H(4)PPh(2))] (1), [(eta(7)-C(7)H(6)PPh(2))Ti(eta(5)
      C(5)H(5))] (2), or [(eta(7)-C(7)H(7))Ti(eta(5)-C(5)H(4)PPh(2))] (3). The use of
      nBuLi/N,N',N',N'',N"-pentamethyldiethylenetriamine (pmdta) allowed us to isolate
      the lithium complexes [(eta(7)-C(7)H(6)Li)Ti(eta(5)-C(5)H(4)Li)] x pmdta (4) and
      [(eta(7)-C(7)H(7))Ti(eta(5)-C(5)H(4)Li)] x pmdta (5), which were structurally
      characterized by X-ray diffraction analyses. Reaction of the monophosphane 3 with
      Mo(CO)(6) and [(tht)AuCl] (tht = tetrahydrothiophene) afforded the
      heterobimetallic complexes [(3)Mo(CO)(5)] (6) and [(3)AuCl] (7) and also the
      trimetallic species [(3)(2)AuCl] (8). The reaction of trans-[PtCl(2)(SEt(2))(2)]
      with the diphosphane 1 led to the formation of cis-[(1)PtCl(2)] (9), whereas the
      complexes trans-[(2)(2)PtCl(2)] (10) and trans-[(3)(2)PtCl(2)] (11) were isolated
      by reaction of two equivalents of the monophosphanes 2 and 3 with trans
      [PtCl(2)(SEt(2))(2)]. The X-ray crystal structures of 6-11 are also reported.

PMID- 19863106
TI  - High resolution mass spectrometry for rapid characterization of combinatorial
      peptide libraries.
AB  - Combinatorial libraries can be characterized in detail by high resolving power
      mass spectrometry. We here demonstrate this for synthetic decapeptide libraries
      using a state-of-the-art 15 T Fourier transform ion cyclotron resonance mass
      spectrometer. Using comparison between predicted and measured spectra, a number
      of metrics can be derived that shed light on the library composition and
      degeneracy of elemental compositions. These techniques can be used to rapidly
      quality control combinatorial synthesis products or follow combinatorial
      libraries in more detail, for instance during binding studies or chemical
      reactions. The methods are in principle equally applicable to the analysis of
      other types of combinatorial libraries.

PMID- 19863107
TI  - A semiempirical capture model for fast neutral reactions at low temperature.
AB  - The description of Titan's chemistry relies strongly on reaction rate data
      collected at room temperature or above. However, the temperature in the
      atmosphere of Titan ranges from 70 to 200 K. We describe here a simple
      theoretical method to extend the available measurements toward those
      temperatures. It is based on the long-range capture theory combined with room
      temperature data. First results are presented for 28 neutral reactions involving
      atomic carbon, CN, CH, and C(2)H radicals and are compared to low-temperature
      Cinetique de Reaction en Ecoulement Supersonique Uniforme measurements. A good
      agreement is observed, to within a factor of 2, for most reactions in the
      temperature range 13-295 K. Predictions are made for reactions of the CN radical
      with hydrocarbons and nitriles of particular importance in Titan's atmosphere.

PMID- 19863110
TI  - Role of halogen bonds in thyroid hormone receptor selectivity: pharmacophore
      based 3D-QSSR studies.
AB  - Most physiological effects of thyroid hormones are mediated by the two thyroid
      hormone receptor subtypes, TRalpha and TRbeta. Several pharmacological effects
      mediated by TRbeta might be beneficial in important medical conditions such as
      obesity, hypercholesterolemia and diabetes, and selective TRbeta activation may
      elicit these effects while maintaining an acceptable safety profile. To
      understand the molecular determinants of affinity and subtype selectivity of TR
      ligands, we have successfully employed a ligand- and structure-guided
      pharmacophore-based approach to obtain the molecular alignment of a large series
      of thyromimetics. Statistically reliable three-dimensional quantitative structure
      activity relationship (3D-QSAR) and three-dimensional quantitative structure
      selectivity relationship (3D-QSSR) models were obtained using the comparative
      molecular field analysis (CoMFA) method, and the visual analyses of the contour
      maps drew attention to a number of possible opportunities for the development of
      analogs with improved affinity and selectivity. Furthermore, the 3D-QSSR analysis
      allowed the identification of a novel and previously unmentioned halogen bond,
      bringing new insights to the mechanism of activity and selectivity of
      thyromimetics.

PMID- 19863108
TI  - Probing biomolecular structures and dynamics of single molecules using in-gel
      alternating-laser excitation.
AB  - Gel electrophoresis is a standard biochemical technique used for separating
      biomolecules on the basis of size and charge. Despite the use of gels in early
      single-molecule experiments, gel electrophoresis has not been widely adopted for
      single-molecule fluorescence spectroscopy. We present a novel method that
      combines gel electrophoresis and single-molecule fluorescence spectroscopy to
      simultaneously purify and analyze biomolecules in a gel matrix. Our method, in
      gel alternating-laser excitation (ALEX), uses nondenaturing gels to purify
      biomolecular complexes of interest from free components, aggregates, and
      nonspecific complexes. The gel matrix also slows down translational diffusion of
      molecules, giving rise to long, high-resolution time traces without surface
      immobilization, which allow extended observations of conformational dynamics in a
      biologically friendly environment. We demonstrated the compatibility of this
      method with different types of single molecule spectroscopy techniques, including
      confocal detection and fluorescence-correlation spectroscopy. We demonstrated
      that in-gel ALEX can be used to study conformational dynamics at the millisecond
      time scale; by studying a DNA hairpin in gels, we directly observed fluorescence
      fluctuations due to conformational interconversion between folded and unfolded
      states. Our method is amenable to the addition of small molecules that can alter
      the equilibrium and dynamic properties of the system. In-gel ALEX will be a
      versatile tool for studying structures and dynamics of complex biomolecules and
      their assemblies.

PMID- 19863109
TI  - Metabolic profiling of human blood serum from treated patients with bipolar
      disorder employing 1H NMR spectroscopy and chemometrics.
AB  - Metabolic profiling employing hydrogen nuclear magnetic resonance (1H NMR)
      spectroscopy and chemometric analysis of human blood serum samples taken from the
      control group (n = 25) and patients with bipolar disorder (n = 25) was performed
      to identify molecular changes related to the disorder and to different drug
      treatments: lithium (n = 15) versus other medications (n = 10). This strategy
      showed significant potential for exploring pathophysiological and toxicological
      features involved in bipolar disorder. The investigated groups (control and
      patients with bipolar disorder under different treatments) could be distinguished
      according to their metabolic profiles, and the main differential metabolites
      found were lipids, lipid-metabolism-related molecules (acetate, choline, and myo
      inositol), and some key amino acids (glutamate, glutamine). Our results suggest
      that some of the 24 identified metabolites may be linked to lithium- and other
      medication-provoked metabolic changes or may even be directly related to the
      disorder. Thus, these findings may contribute to paving the way for future
      studies aiming at identifying potential biomarkers for bipolar disorder.

PMID- 19863111
TI  - Biochemical characterization of the RNase II family of exoribonucleases from the
      human pathogens Salmonella typhimurium and Streptococcus pneumoniae.
AB  - Maturation, turnover, and quality control of RNA are performed by many different
      classes of ribonucleases. Escherichia coli RNase II is the prototype of the RNase
      II family of ribonucleases, a ubiquitous family of hydrolytic, processive 3' -->
      5' exonucleases crucial in RNA metabolism. RNase R is a member of this family
      that is modulated in response to stress and has been implicated in virulence. In
      this work, RNase II-like proteins were characterized in the human pathogens
      Salmonella typhimurium and Streptococcus pneumoniae. By sequence analysis, only
      one member of the RNase II family was identified in S. pneumoniae, while both
      RNase II and RNase R were found in Sa. typhimurium. These enzymes were cloned,
      expressed, purified, and characterized with regard to their biochemical features
      and modular architecture. The specificity of substrates and the final products
      generated by the enzymes were clearly demonstrated. Sa. typhimurium RNase II and
      RNase R behaved essentially as their respective E. coli counterparts. We have
      shown that the only hydrolytic RNase found in S. pneumoniae was able to degrade
      structured RNAs as is the case with E. coli RNase R. Our results further showed
      that there are differences with regard to the activity and ability to bind RNA
      from enzymes belonging to two distinct pneumococcal strains, and this may be
      related to a single amino acid substitution in the catalytic domain. Since
      ribonucleases have not been previously characterized in S. pneumoniae or Sa.
      typhimurium, this work provides an important first step in the understanding of
      post-transcriptional control in these pathogens.

PMID- 19863113
TI  - Measuring self-diffusion coefficients up to 1500 K: a powerful tool to
      investigate the dynamics and the local structure of inorganic melts.
AB  - Self-diffusion is a fundamental property of liquid dynamics that also provides
      important structural information. To explore the dynamics in inorganic melts with
      high liquidus temperature, we propose a new setup based on pulsed field gradient
      NMR combined with laser heating that makes possible in situ self-diffusion
      coefficient measurements up to 1500 K. Applied to several corrosive molten
      fluorides in a wide range of compositions and temperature, we have evidenced the
      different key parameters of their motion along with their structural
      characteristics. In alkali fluorides, the self-diffusion coefficient of fluorine
      depends slightly on the composition compared to the temperature, displaying these
      systems as an ideal bath of polarizable hard spheres. In contrast, self-diffusion
      in rare earth and alkali fluorides mixtures presents a complicated balance
      between temperature and the network-forming process of the ionic long-lived
      units. These results open wide perspectives in the study of high temperature
      liquids.

PMID- 19863112
TI  - Structural basis of the aberrant receptor binding properties of hagfish and
      lamprey insulins.
AB  - The insulin from the Atlantic hagfish (Myxine glutinosa) has been one of the most
      studied insulins from both a structural and a biological viewpoint; however, some
      aspects of its biology remain controversial, and there has been no satisfying
      structural explanation for its low biological potency. We have re-examined the
      receptor binding kinetics, as well as the metabolic and mitogenic properties, of
      this phylogenetically ancient insulin, as well as that from another extant
      representative of the ancient chordates, the river lamprey (Lampetra
      fluviatilis). Both insulins share unusual binding kinetics and biological
      properties with insulin analogues that have single mutations at residues that
      contribute to the hexamerization surface. We propose and demonstrate by
      reciprocal amino acid substitutions between hagfish and human insulins that the
      reduced biological activity of hagfish insulin results from unfavorable
      substitutions, namely, A10 (Ile to Arg), B4 (Glu to Gly), B13 (Glu to Asn), and
      B21 (Glu to Val). We likewise suggest that the altered biological activity of
      lamprey insulin may reflect substitutions at A10 (Ile to Lys), B4 (Glu to Thr),
      and B17 (Leu to Val). The substitution of Asp at residue B10 in hagfish insulin
      and of His at residue A8 in both hagfish and lamprey insulins may help compensate
      for unfavorable changes in other regions of the molecules. The data support the
      concept that the set of unusual properties of insulins bearing certain mutations
      in the hexamerization surface may reflect those of the insulins evolutionarily
      closer to the ancestral insulin gene product.

PMID- 19863114
TI  - Total synthesis of the putative structure of lucentamycin A.
AB  - A rapid and stereoselective enolate-Claisen rearrangement provides access to the
      4-ethylidene-3-methylproline (Emp) subunit of lucentamycin A. Synthesis of the
      putative structure of the cytotoxic natural product suggests the need for
      structural revision.

PMID- 19863115
TI  - Kinetics of methane-ethane gas replacement in clathrate-hydrates studied by time
      resolved neutron diffraction and Raman spectroscopy.
AB  - The kinetics of CH(4)-C(2)H(6) replacement in gas hydrates has been studied by in
      situ neutron diffraction and Raman spectroscopy. Deuterated ethane structure type
      I (C(2)H(6) sI) hydrates were transformed in a closed volume into methane-ethane
      mixed structure type II (CH(4)-C(2)H(6) sII) hydrates at 5 MPa and various
      temperatures in the vicinity of 0 degrees C while followed by time-resolved
      neutron powder diffraction on D20 at ILL, Grenoble. The role of available surface
      area of the sI starting material on the formation kinetics of sII hydrates was
      studied. Ex situ Raman spectroscopic investigations were carried out to
      crosscheck the gas composition and the distribution of the gas species over the
      cages as a function of structure type and compared to the in situ neutron
      results. Raman micromapping on single hydrate grains showed compositional and
      structural gradients between the surface and core of the transformed hydrates.
      Moreover, the observed methane-ethane ratio is very far from the one expected for
      a formation from a constantly equilibrated gas phase. The results also prove that
      gas replacement in CH(4)-C(2)H(6) hydrates is a regrowth process involving the
      nucleation of new crystallites commencing at the surface of the parent C(2)H(6)
      sI hydrate with a progressively shrinking core of unreacted material. The time
      resolved neutron diffraction results clearly indicate an increasing diffusion
      limitation of the exchange process. This diffusion limitation leads to a
      progressive slowing down of the exchange reaction and is likely to be responsible
      for the incomplete exchange of the gases.

PMID- 19863116
TI  - Photogeneration of nitrosyl linkage isomers in octahedrally coordinated platinum
      complexes in the red spectral range.
AB  - Octahedrally coordinated platinum nitrosyl complexes
      [Pt(NH(3))(4)(NO(3))(NO)](NO(3))(2) (1) and
      [Pt(NH(3))(4)(SO(4))(NO)](HSO(4))(CH(3)CN) (2) undergo linkage isomerization at
      temperatures below 130 K when excited with red light. Irradiation in the spectral
      range of 570-800 nm results in an inversion of the NO ligand from a Pt-NO to a Pt
      ON configuration. The metastable state Pt-ON can be reverted back to the ground
      state (GS) Pt-NO by irradiation with blue-green or infrared light or by heating
      above 130 K. The characteristic shift of the nu(NO) stretching vibration from
      1744 to 1815 cm(-1) in 1 and from 1714 to 1814 cm(-1) in 2 allowed the
      unambiguous identification of the respective nitrosyl isomers. Up to 26% of the
      complexes of 1 and 20% of 2 may be photochemically excited toward the metastable
      state (MS). Using X-ray crystallography and DFT calculations, it is shown that
      the Pt-NO in these {MNO}(8) complexes exhibits a bent arrangement with a Pt-N-O
      angle in the range of 117-120 degrees. As a consequence and in contrast to the
      known {MNO}(6) complexes only one metastable linkage isomer Pt-ON with a
      correspondingly bent Pt-O-N arrangement is formed, as evidenced by spectroscopy
      and DFT calculations. The calculated partial density of states shows that the
      charge transfer transition Pt(5d) --> pi(star)(NO) is responsible for the
      formation of the metastable state.

PMID- 19863117
TI  - Peculiar binding modes of a ligand with two adjacent beta-diiminato binding sites
      in alkali and alkaline-earth metal chemistry.
AB  - Reaction of the diprotic ligand [Xanthdim]H(2) (a ligand system where two
      adjacent beta-dialdimine units are linked by a xanthyl backbone) with 2 equiv of
      potassium hydride or benzylcesium gave access to bimetallic alkali metal
      complexes. These complexes were structurally characterized by X-ray diffraction,
      which showed that the beta-diiminato units are orientated in a W-conformation.
      Treatment with 2 equiv of Mg[N(SiMe(3))(2)](2)(THF)(2) led to the formation of
      the heteroleptic complex [Xanthdim][MgN(SiMe(3))(2)(THF)](2), that crystallized
      as a highly strained monomer. The heteroleptic Mg complex is remarkably stable
      against ligand exchange but is not active in CO(2)/cyclohexene oxide
      copolymerization. Reaction with Ca[N(SiMe(3))(2)](2)(THF)(2) gave the homoleptic
      complex [Xanthdim][Ca(THF)]. Both alkaline-earth metal complexes display
      considerable distortions in their solid state structure.

PMID- 19863118
TI  - Synthesis, structure, and stability of adducts between phosphide and amide anions
      and the Lewis acids borane, tris(pentafluorophenyl)borane, and
      tris(pentafluorophenyl)alane.
AB  - The phosphinoborane adduct H(3)P x B(C(6)F(5))(3) can be deprotonated using
      LiN(SiMe(3))(2) to give the phosphidoborate salt Li[H(2)PB(C(6)F(5))(3)], which
      was converted to the phosphidodiborates Li[H(2)P{B(C(6)F(5))(3)}(2)] and
      Li[H(2)P{B(C(6)F(5))(3)}{BH(3)}] by treatment with an equivalent of
      B(C(6)F(5))(3) or Me(2)S.BH(3), respectively. A series of anions of the form
      [RR'P{M(C(6)F(5))(3)}{BH(3)}](-), where R = R' = Ph or R= (t)Bu, R' = H, and M =
      B or Al, were prepared (through treatment of salts Li[RR'P(BH(3))] with the
      corresponding Lewis acid) and characterized using multinuclear NMR, elemental
      analysis and X-ray crystallography. The solid state structures of
      [Li(Et(2)O)(x)][Ph(2)P{M(C(6)F(5))(3)}{BH(3)}] exhibit eta(2)-bonding of the
      BH(3) group to the cationic lithium center. The attempted preparation of an
      analogous series with amide cores of the form [R(2)N{B(C(6)F(5))(3)}{BH(3)}](-)
      proved unsuccessful; among the competing reaction pathways hydride abstraction
      occurred preferentially to yield Li[HB(C(6)F(5))(3)] and dimers or higher
      oligomers with the composition (R(2)NBH(2))(n).

PMID- 19863119
TI  - Total synthesis of racemic laurenditerpenol, an HIF-1 inhibitor.
AB  - The convergent total synthesis of the HIF-1 inhibitor laurenditerpenol 1 and its
      diastereomer 1' is reported. The key step involves the Julia-Kocienski
      olefination-reduction process between the sulfone 55 and the aldehyde 54. The
      unusual trimethylated oxanorbornane sulfone 55 was successfully synthesized from
      the known exo Diels-Alder adduct 24 of 2,5-dimethylfuran 7 and maleic anhydride
      23 in 8 steps. The aldehyde 54 was prepared by ring-opening and elaboration of
      lactone 41. In addition, four analogues of 1 were also successfully synthesized
      for biological testing.

PMID- 19863120
TI  - Evidence of critical cooling rates in the nonisothermal crystallization of
      triacylglycerols: a case for the existence and selection of growth modes of a
      lipid crystal network.
AB  - The isoconversional method, a model-free analysis of the kinetics of liquid-solid
      transformations, was used to determine the effective activation energy of the
      nonisothermal crystallization of melts of pure and complex systems of
      triacylglycerols (TAGs). The method was applied to data from differential
      scanning calorimetry (DSC) measurements of the heat of crystallization of
      purified 1,3-dilauroyl-2-stearoyl-sn-glycerol (LSL) and commercially available
      cocoa butter melts. The method conclusively demonstrated the existence of
      specific growth modes and critical rates of cooling at specific degrees of
      conversion. The existence of critical rates suggests that the crystallization
      mechanism is composed of growth modes that can be effectively treated as mutually
      exclusive, each being predominant for one range of cooling rates and extent of
      conversion. Importantly, the data suggests that knowledge of the critical cooling
      rates at specific rates of conversion can be exploited to select preferred growth
      modes for lipid networks, with concomitant benefits of structural organization
      and resultant physical functionality. Differences in transport phenomena induced
      by different cooling rates suggest the existence of thresholds for particular
      growth mechanisms and help to explain the overall complexity of lipid
      crystallization. The results of this model-free analysis may be attributed to the
      relative importance of nucleation and growth at different stages of
      crystallization. A mechanistic explanation based on the competing effects of the
      thermodynamic driving force and limiting heat and transport phenomena is provided
      to explain the observed behavior. This work, furthermore, offers satisfactory
      explanations for the noted effect of cooling-rate-induced changes in the physical
      functionality of lipid networks.

PMID- 19863121
TI  - Rossinones A and B, biologically active meroterpenoids from the Antarctic
      ascidian, Aplidium species.
AB  - Rossinones A (1) and B (2), biologically active meroterpene derivatives, were
      isolated from an Antarctic collection of the ascidian Aplidium species and
      structurally characterized with spectroscopic methods. The absolute configuration
      of 1 was deduced by using the modified Mosher method. The rossinones exhibit anti
      inflammatory, antiviral and antiproliferative activities.

PMID- 19863122
TI  - Use of the SPhos ligand to suppress racemization in arylpinacolboronate ester
      Suzuki couplings involving alpha-amino acids. Synthesis of biaryl derivatives of
      4-hydroxyphenylglycine, tyrosine, and tryptophan.
AB  - Alpha-amino acid derivatives, particularly those of phenylglycine, can suffer
      significant racemization in Suzuki couplings. When arylpinacolboronate esters are
      used as coupling partners this unwanted side reaction can be suppressed by the
      use of Pd(OAc)(2) as Pd(0) source, in the presence of Buchwald's SPhos ligand.
      The syntheses of biaryl amino acids of tyrosine, phenylglycine, and tryptophan,
      including Phg-Trp units similar to those found in the chloropeptin family of
      natural products, are reported.

PMID- 19863123
TI  - Synthesis of an unlocked nucleic acid terpyridine monomer and binding of divalent
      metal ion in nucleic acid duplexes.
AB  - Herein we present the synthesis and thermal stability studies of modified
      oligonucleotides containing an unlocked nucleic acid (UNA) terpyridine monomer.
      Incorporation of this monomer into both strands of a DNA duplex allowed
      reversible thermal stability modulation upon addition or withdrawal of divalent
      metal ions. A likely explanation of this phenomenon is interstrand complexation
      between two terpyridine units and a metal ion. This system could be useful in the
      development of nanoscale devices based on DNA hybridization.

PMID- 19863125
TI  - Amyloid-like self-assembly of peptide sequences from the adenovirus fiber shaft:
      insights from molecular dynamics simulations.
AB  - The self-assembly of peptides and proteins into nanostructures is related to the
      fundamental problems of protein folding and misfolding and has potential
      applications in medicine, materials science and nanotechnology. Natural peptides,
      corresponding to sequence repeats from self-assembling proteins, may constitute
      elementary building blocks of such nanostructures. In this work, we study by
      implicit-solvent replica-exchange simulations the self-assembly of two
      amyloidogenic sequences derived from the naturally occurring fiber shaft of the
      adenovirus, the octapeptide NSGAITIG (asparagine-serine-glycine-alanine
      isoleucine-threonine-isoleucine-glycine) and its hexapeptide counterpart, GAITIG.
      In accordance with their amyloidogenic capacity, both peptides form readily
      intermolecular beta-sheets, stabilized by extensive main- and side-chain contacts
      involving the C-terminal moieties (segments 3-8 and 2-6, respectively). The
      structural and energetic properties of these sheets are analyzed extensively. The
      N-terminal residues Asn1 and Ser2 of the octapeptide remain disordered in the
      sheets, suggesting that these residues are exposed at the exterior of the fibrils
      and accessible. On the basis of insight provided by the simulations, cysteine
      residues were recently substituted at positions 1 and 2 of NSGAITIG; the newly
      designed peptides maintain their amyloidogenic properties and can bind to silver,
      gold and platinum nanoparticles [Kasotakis et al. Biopolymers 2009, 92, 164-172].
      Computational investigation can identify suitable positions for rational
      modification of peptide building blocks, aiming at the fabrication of novel
      biomaterials.

PMID- 19863124
TI  - Interaction of poloxamers with liposomes: an isothermal titration calorimetry
      study.
AB  - The interaction between lipid bilayers and poloxamers has recently attracted much
      attention, and contradicting effects of poloxamers have been revealed on the
      integrity of lipid membranes; poloxamers are reported to be either effective
      sealants or permeabilizers of cell membranes depending on the cell type. To
      elucidate poloxamer-membrane interactions, we study the roles played by the lipid
      bilayer phase structure, poloxamer concentration, and temperature using
      isothermal titration calorimetry (ITC). Our results indicate that the lipid
      bilayer phase structure plays a critical role in its interaction with poloxamers.
      Poloxamers are found to partition only into fluid-phase, not gel-phase,
      membranes. Moreover, the partitioning of poloxamers into fluid-phase liposomes
      increases with temperature, owing to the enhancement in both the membrane
      fluidity and the hydrophobicity of the poloxamer at elevated temperatures. Our
      ITC results also point to a saturation concentration of poloxamers, below which
      poloxamers can partition into a lipid bilayer without disrupting liposomes and
      above which they instead disintegrate liposomes into micelles. To address the
      long-standing question as to whether poloxamers migrate through the lipid bilayer
      after their adsorption onto preformed liposomes, two ITC protocols are used to
      cross-validate the distribution of poloxamers over the two leaflets in the
      bilayer. We find that on a short timescale (approximately 200 min) poloxamers
      partition into the outer leaflet of the fluid-phase lipid bilayer without much
      interactions with the inner leaflet. However, on a longer timescale (38 h), they
      are found to migrate through the bilayer and eventually establish an even
      distribution in both the inner and outer leaflets of the membrane.

PMID- 19863126
TI  - Molecular structure of 9H-adenine tautomer: gas-phase electron diffraction and
      quantum-chemical studies.
AB  - Molecular geometry of 9H-adenine tautomer was calculated by MP2 method using
      several basis sets (up to cc-pVQZ). According to the results of all quantum
      chemical calculations, the molecule has an essentially planar heavy-atom skeleton
      and a quasi-planar amino group. Since the bond lengths of adenine are of similar
      magnitude, the structural problem could not be solved by the gas-phase electron
      diffraction (GED) method alone. Therefore the differences between similar bond
      lengths derived from ab initio geometry and rotational constants from microwave
      (MW) spectroscopic study (Brown, R. D.; et al. Chem. Phys. Lett. 1989, 156, 61)
      were used as supplementary data. To bring the data of the different experimental
      methods to the same basis (equilibrium structure), GED internuclear distances
      r(a) and MW rotational constants B(0)((i)) (i = A, B, C) were corrected for
      vibrational effects. Harmonic and anharmonic corrections were estimated using
      quadratic and cubic force constants from MP2/cc-pVTZ calculations. Anharmonic
      corrections to r(a) distances were calculated using improved theoretical
      approximation. The molecular structure of 9H-adenine is determined experimentally
      for the first time. Since the GED intensities are not sensitive to hydrogen
      positions, and small deviations of skeleton cannot be determined with appropriate
      uncertainty, the molecular configuration of adenine was assumed to be planar
      (C(s) symmetry) in the GED analysis. The main equilibrium structural parameters
      determined from GED data supplemented by rotational constants and results of
      MP2/cc-pVTZ calculations are the following (bond lengths in angstroms and bond
      angles in degrees with 3sigma in parentheses): r(e)(C2-N1) = 1.344(3), r(e)(C2
      N3) = 1.330(3), r(e)(C4-N3) = 1.333(3), r(e)(C4-C5) = 1.401(3), r(e)(C5-C6) =
      1.409(3), r(e)(C6-N1) = 1.332(3), r(e)(C5-N7) = 1.380(4), r(e)(C8-N7) = 1.319(3),
      r(e)(C8-N9) = 1.371(4), r(e)(C4-N9) = 1.377(4), r(e)(C6-N10) = 1.357(4),
      angle(e)(N1-C2-N3) = 129.0(1), angle(e)(C2-N3-C4) = 111.0(1), angle(e)(N3-C4-C5)
      = 127.2(1), angle(e)(C4-C5-N7) = 111.9(2), angle(e)(C5-N7-C8) = 103.4(2), and
      angle(e)(C5-C6-N10) = 121.9(2). The determined experimental bond lengths of
      adenine are in good agreement with those from MP2 calculations and with
      experimental bond lengths of pyrimidine and 1H-imidazole (except for the C-C
      double bond in imidazole). Being close to typical aromatic internuclear
      distances, the obtained C-C and C-N bond lengths indicate the aromatic nature of
      this molecule. The calculated aromaticity indexes (GIAO-MP2/cc-pVTZ) confirm this
      statement.

PMID- 19863127
TI  - Supersymmetric quantum mechanics, excited state energies and wave functions, and
      the Rayleigh-Ritz variational principle: a proof of principle study.
AB  - In addition to ground state wave functions and energies, excited states and their
      energies are also obtained in a standard Rayleigh-Ritz variational calculation.
      However, their accuracy is generally much lower. Using the super-symmetric (SUSY)
      form of quantum mechanics, we show that better accuracy and more rapid
      convergence can be obtained by taking advantage of calculations of the ground
      states of higher sector SUSY Hamiltonians, followed by application of the SUSY
      "charge operators". Our proof of principle study uses a general family of one
      dimensional anharmonic oscillator models. We first obtain the exact, analytic
      ground states for a general family of anharmonic systems. We give the general,
      factorized form of the Hamiltonian for the hierarchy that arises in SUSY theory.
      The "charge" operators can then be used to convert states among the sectors. We
      illustrate the approach with two specific anharmonic oscillator models. Using the
      ground state of the second sector Hamiltonian, we show that the corresponding
      excited state energies and wave functions of the first sector are accurately
      obtained by applying the charge operators, using significantly smaller basis sets
      than are required in a standard variational approach applied to the original
      Schrodinger equation. This is a consequence of the higher accuracy of the
      Rayleigh-Ritz variational method when applied for ground states.

PMID- 19863129
TI  - Effects of molecule stabilization energies on radical reactions: G3 and G3(MP2)
      model chemistries applied to benzylic systems.
AB  - We have carried out G3 and G3(MP2) calculations of the molecule stabilization
      energies (MSEs) brought about by 11 common substituent groups in the meta and
      para positions of benzyl fluoride. We find that MSE is a function of the tendency
      of the substituent to donate or to withdraw electrons, such that a classic
      Hammett plot can be drawn. We propose that, in general, the direction of the
      benzylic Z-X dipole of YC6H4ZX is the major factor controlling the sign of the
      slope of Hammett plots of benzylic atom abstractions by radicals. When the Z-X
      dipole is pointed away from the substituted ring, electron withdrawing
      substituents destabilize the molecule, contributing to a decrease of the Z-X bond
      dissociation energy, and electron donating substituents stabilize it. The reverse
      is true when the dipole is reversed. This proposal is supported by 13C NMR
      results and by a survey of relevant benzylic and quasi-benzylic hydrogen or
      halogen atom abstractions studied experimentally. Calculations at the G3 level of
      theory demonstrate an increase in the bond dissociation energy of p-YC6H4CH2-H
      with increasing electron withdrawing ability of Y, contrary to results of
      previous lower level calculations. MSE values of substituted benzyl fluorides (p
      YC6H4CH2F) correlate well with allylic MSE (trans-YCH=CHCH2F) and quantify the
      relative efficacy of transmission of electronic effects by vinylogy.

PMID- 19863128
TI  - The role of key amino acids in the photoactivation pathway of the Synechocystis
      Slr1694 BLUF domain.
AB  - BLUF (blue light sensing using FAD) domains belong to a novel group of blue light
      sensing receptor proteins found in microorganisms. We have assessed the role of
      specific aromatic and polar residues in the Synechocystis Slr1694 BLUF protein by
      investigating site-directed mutants with substitutions Y8W, W91F, and S28A. The
      W91F and S28A mutants formed the red-shifted signaling state upon blue light
      illumination, whereas in the Y8W mutant, signaling state formation was abolished.
      The W91F mutant shows photoactivation dynamics that involve the successive
      formation of FAD anionic and neutral semiquinone radicals on a picosecond time
      scale, followed by radical pair recombination to result in the long-lived
      signaling state in less than 100 ps. The photoactivation dynamics and quantum
      yield of signaling state formation were essentially identical to those of wild
      type, which indicates that only one significant light-driven electron transfer
      pathway is available in Slr1694, involving electron transfer from Y8 to FAD
      without notable contribution of W91. In the S28A mutant, the photoactivation
      dynamics and quantum yield of signaling state formation as well as dark recovery
      were essentially the same as in wild type. Thus, S28 does not play an essential
      role in the initial hydrogen bond switching reaction in Slr1694 beyond an
      influence on the absorption spectrum. In the Y8W mutant, two deactivation
      branches upon excitation were identified: the first involves a neutral
      semiquinone FADH(*) that was formed in approximately 1 ps and recombines in 10 ps
      and is tentatively assigned to a FADH(*)-W8(*) radical pair. The second
      deactivation branch forms FADH(*) in 8 ps and evolves to FAD(*-) in 200 ps, which
      recombines to the ground state in about 4 ns. In the latter branch, W8 is
      tentatively assigned as the FAD redox partner as well. Overall, the results are
      consistent with a photoactivation mechanism for BLUF domains where signaling
      state formation proceeds via light-driven electron and proton transfer from Y8 to
      FAD, followed by a hydrogen bond rearrangement and radical pair recombination.

PMID- 19863131
TI  - Size- and temperature-dependent magnetic response of molecular cage clusters:
      manganese-doped tin clusters.
AB  - Endohedral clusters, formed by incorporating a single Mn atom into a cage of tin
      atoms, have been generated in the gas phase. Mass spectrometry reveals that a
      cage size of 10 tin atoms is necessary for the efficient incorporation of one Mn
      atom. Some of the cluster compounds with one Mn atom attached to the tin clusters
      display large intensities compared to the pure tin clusters, indicating that the
      compound clusters are particularly stable. The manganese-doped tin cluster
      assemblies Mn@Sn12, Mn@Sn13, and Mn@Sn15 have been further analyzed within a
      molecular beam magnetic deflection experiment. Interestingly, although the effect
      of the magnetic field on the behavior of Mn@Sn12 is quite different from that of
      Mn@Sn13 and Mn@Sn15, the magnetic dipole moments are the same within the
      uncertainty of the measurements. Magnetic dipole moments have been found in close
      agreement with the spin quantum number S = 5/2 predicted by theory for Mn@Sn12,
      indicating that the magnetic moment of the Mn atom is not quenched. This supports
      the idea that within a tin cluster cage a single Mn atom can be encapsulated,
      resulting in the formation of endohedral clusters consisting of a central Mn2+
      ion surrounded by a particularly stable Zintl-ion cage Sn(N)(2-). The observed
      molecular beam profiles indicate that at a nozzle temperature of 55 K the
      magnetic moment is strongly locked to the molecular framework of Mn@Sn12; in
      contrast, the magnetic moment of Mn@Sn13 and Mn@Sn15 tends to align with the
      magnetic field. The experiments therefore demonstrate that the size of a
      presumably nonmagnetic cluster cage might have a fundamental influence on the
      magnetization dynamics of paramagnetic species. The influence of vibrational
      excitation on the Stern-Gerlach profile of Mn@Sn12 is further analyzed, and it is
      shown that the behavior of Mn@Sn12 at elevated nozzle temperatures changes
      continuously toward a nonlocked moment, pointing to size- and temperature
      dependent magnetization dynamics.

PMID- 19863130
TI  - Ultrafast excitation of molecular adsorbates on flash-heated gold surfaces.
AB  - An ultrafast flash-thermal conductance technique is used to study energy transfer
      from a flash-heated polycrystalline Au(111) surface to adsorbed thiolate self
      assembled monolayers (SAMs). The focus is on understanding energy transfer
      processes to parts of SAM molecules situated within a few carbon atoms of the Au
      surface, by probing specific SAM functional groups with vibrational sum-frequency
      generation (SFG) spectroscopy. The SFG intensity drop after flash-heating for
      benzenethiol (BT) CH-stretch transitions shows a substantial overshoot lasting
      several tens of picoseconds before BT and Au equilibrate at a higher temperature
      estimated at 600 degrees C. The thermal redshift of BT CH-stretch transitions
      also shows an overshoot. Other aromatic molecules and aliphatic molecules such as
      cyclohexanethiol (CHT) and hexanethiol (C6) have an overshoot as well. A model is
      proposed where the overshoot is primarily the result of hot surface electrons
      existing only during the flash-heating pulses. The intensity overshoot is caused
      by electron excitation of the probed vibrations and the redshift overshoot is
      caused by electron excitation of lower-energy vibrations anharmonically coupled
      to the probed vibration. Although electron excitation causes a substantial
      perturbation, up to 50% in some cases, of the SFG signal, the total amount of
      energy deposited into SAMs by electrons is much smaller than the heat transferred
      by Au surface phonons. Studies of a variety of molecular structures including
      substituted benzenes, biphenyl and terphenyl, and benzene rings connected to the
      Au surface by alkane linkers show that the likelihood of electron excitation
      becomes small for distances of 4-5 carbon atoms above the surface.

PMID- 19863132
TI  - Reactions of group 14 metal atoms with acetylene: a matrix isolation infrared
      spectroscopic and theoretical study.
AB  - Laser-ablated group 14 metal atoms have been codeposited at 4 K with acetylene in
      excess argon. Products, Ge(C2H2), HGeCCH, Sn(C2H2), Sn2CCH2, HSnCCH, and HPbCCH,
      have been formed in the present experiments and characterized using infrared
      spectroscopy on the basis of the results of the isotopic shifts, mixed isotopic
      splitting patterns, stepwise annealing, the change of reagent concentration and
      laser energy, and the comparison with theoretical predictions. Density functional
      theory calculations have been performed on these molecules. The agreement between
      the experimental and the calculated vibrational frequencies, relative absorption
      intensities, and isotopic shifts supports the identification of these molecules
      from the matrix infrared spectra. Plausible reaction mechanisms have been
      proposed to account for the formation of these molecules.

PMID- 19863133
TI  - X-ray absorption and emission spectroscopy of Cr(III) (hydr)oxides: analysis of
      the K-pre-edge region.
AB  - Pre-edge spectral features below the main X-ray absorption K-edge of transition
      metals show a pronounced chemical sensitivity and are promising sources of
      structural information. Nevertheless, the use of pre-edge analysis in applied
      research is limited because of the lack of definite theoretical peak-assignments.
      The aim of this study was to determine the factors affecting the chromium K-pre
      edge features in trivalent chromium-bearing oxides and oxyhydroxides. The
      selected phases varied in the degree of octahedral polymerization and the degree
      of iron-for-chromium substitution in the crystal structure. We investigated the
      pre-edge fine structure by means of high-energy-resolution fluorescence detected
      X-ray absorption spectroscopy and by 1s2p resonant X-ray emission spectroscopy.
      Multiplet theory and full multiple-scattering calculations were used to analyze
      the experimental data. We show that the chromium K-pre-edge contains localized
      and nonlocalized transitions. Contributions arising from nonlocalized metal-metal
      transitions are sensitive to the nearest metal type and to the linkage mode
      between neighboring metal octahedra. Analyzing these transitions opens up new
      opportunities for investigating the local coordination environment of chromium in
      poorly ordered solids of environmental relevance.

PMID- 19863134
TI  - 500 nm system of RbCs: assignments and intensity anomalies.
AB  - We have investigated the RbCs 500 nm system by mass-resolved resonance enhanced
      two-photon ionization in a cold molecular beam. The 4 3Pi0 v' = 10-39, 4 3Pi1 v'
      = 14-28, and 6 1Sigma+ v' = 12-28 <-- X 1Sigma+ v'' = 0 transitions have been
      observed and assigned for the first time. The 4 3Pi0 v' <-- X 1Sigma+ v'' = 0
      transitions abnormally show double maxima of the vibronic-band intensity
      distribution around v' = 22 and 38. The intensities of the transitions to the
      lower vibrational levels (4 3Pi0 v' = 10-32) are explained well by the direct
      transitions from the X 1Sigma+ v'' = 0 level following the Franck-Condon
      principle. The transitions to the higher vibrational levels (4 3Pi0 v' > or = 33)
      borrow intensities through the interaction with nearby 6 1Sigma+ perturber
      levels.

PMID- 19863135
TI  - Relativistic interactions in the radical pair model of magnetic field sense in
      CRY-1 protein of Arabidopsis thaliana.
AB  - Experimentally, it has been shown that magnetic field sensitivity in living
      organisms is connected to the presence of blue-light photoreceptor cryptochromes.
      Cryptochromes transduce a light signal through a chain of chemical reactions
      involving the formation of intermediate biradicals. It was proposed that an
      external magnetic field affects the interconversion between singlet and triplet
      states of biradicals and thus interferes with the signal transduction chain.
      Theoretical modeling of this process requires an accurate evaluation of all
      interactions important for singlet-triplet interconversion: electron-electron,
      spin-orbit, spin-spin, hyperfine, and Zeeman. In the current study we investigate
      these interactions at the CIS level of theory applied to representative fragments
      of the CRY-1 protein in the plant Arabidopsis thaliana. We find, in contrast to
      previous simplified modeling (O. Efimova, O.; Hore, P. J. Biophys. J. 2008, 94,
      1565), that the spin-spin interaction is significantly larger than the "exchange"
      interaction. Thus it is not canceled by the latter but rather dies off with the
      inter-radical separation. Also, we find that the spin-orbit interaction can play
      a significant role in singlet-triplet interconversion for short inter-radical
      distances, and the hyperfine interaction becomes the only coupling interaction
      for long inter-radical distances.

PMID- 19863136
TI  - Nature of low-lying excited states in H-aggregated perylene bisimide dyes:
      results of TD-LRC-DFT and the mixed exciton model.
AB  - We characterize the nature of the low-lying excited states in H-aggregated
      perylene bisimide (PBI) dyes in terms of the recently proposed long-range
      corrected density functional theory (LRC-DFT) and the mixed intramolecular
      Frenkel exciton (FE) and the intermolecular charge-transfer exciton (CTE) model.
      The singlet vertical excitation energies of H-aggregated PBI dimers and multimers
      are theoretically evaluated by considering the aggregation details. It is found
      that the dimer absorption follows closely the spectra of PBI aggregates in
      solution and demonstrates strong mixing of two kinds of excitons. The
      experimentally observed low-energy absorption peak near 2.3 eV should not be a
      pure CT state but a mixed excitonic state. To model the electronic excitations of
      H-aggregated PBI multichromophoric oligomers, we adopt a mixed FE-CTE model
      Hamiltonian, whose microscopic parameters are determined from LRC-DFT/TD-LRC-DFT
      calculations performed on an individual chromophore or a chromophore pair. By
      involving four to five PBI chromophores, we have succeeded in reproducing the
      experimental trends of optical properties in PBI stacking, such as the large blue
      shift of the absorption band, the mixed FE-CTE nature of the low-energy
      absorption bands, and the large Stokes shift of emission spectra. The long-range
      correction on DFT exchange-correlation energy functionals is crucial to correctly
      evaluate the photophysical characteristics of pi-pi stacks.

PMID- 19863137
TI  - Anisotropy of the thermal conductivity of stretched amorphous polystyrene in
      supercritical carbon dioxide studied by reverse nonequilibrium molecular dynamics
      simulations.
AB  - The thermal conductivity (lambda) of stretched amorphous atactic polystyrene (PS)
      swollen in supercritical carbon dioxide (sc CO(2)) has been investigated over a
      wide temperature, pressure, and concentration range. Nonequilibrium molecular
      dynamics simulations with a full atomistic force-field have been employed to
      calculate the thermal conductivity of neat stretched PS and of different mixtures
      of supercritical CO(2) with stretched PS. As the energy transport in PS parallel
      and perpendicular to the stretching direction differs, an anisotropy in the
      thermal conductivity occurs. The magnitude of lambda is enhanced with an
      increasing number of carbon-carbon backbone bonds oriented parallel to the
      direction of the heat transport. The degrees of freedom in the side chain of the
      polymer are rather unimportant for the thermal conductivity. To understand the
      conditions leading either to an equivalence or nonequivalence of the system
      degrees of freedom for the heat transport, we have analyzed lambda of PS, CO(2),
      binary PS-CO(2) mixtures and other model systems as a function of the bond
      constraints in the computational model. Furthermore, we have commented on
      differences in the thermal conductivity provided either by a vibrational energy
      transfer or by collisions.

PMID- 19863138
TI  - Detailed single-molecule spectroelectrochemical studies of the oxidation of
      conjugated polymers.
AB  - Single-particle fluorescence spectroelectrochemistry was used to investigate the
      electrochemical oxidation of isolated, immobilized particles of the conjugated
      polymers BEH-PPV and MEH-PPV at an indium tin oxide (ITO) electrode immersed in
      an electrolyte solution. Two types of particles were investigated: (i) polymer
      single molecules (SM) and (ii) nanoparticle (NP) aggregates of multiple polymer
      single molecules. For the BEH-PPV polymer, the observation of nearly identical
      lowest oxidation potentials for different SM in the ensemble is evidence for
      effective electrostatic screening by the surrounding electrolyte solution. A
      combination of Monte Carlo simulations and application of Poisson-Boltzmann
      solvers were used to model the charging of polymer single molecules and
      nanoparticles in the electrochemical environment. The results indicate that the
      penetration of electrolyte anions into the polymer nanoparticles is necessary to
      produce the observed narrow fluorescence quenching vs oxidation potential curves.
      Finally, fluorescence-lifetime single-molecule spectroelectrochemical (SMS-EC)
      data revealed that at low potential an excited state reduction process (i.e.,
      electron transfer from ITO to the polymer) is probably the dominant fluorescence
      quenching process.

PMID- 19863139
TI  - Coupling effect between mechanical loading and chemical reactions.
AB  - This paper offers a theoretical explanation of the coupling effect phenomenon
      between mechanical loading and chemical reactions based on linear nonequilibrium
      thermodynamics and also discusses the classical method of obtaining restrictions
      on the phenomenological coefficients. The question whether static or dynamic
      loading influences biochemical processes is addressed-the necessity of dynamic
      loading as a stimulatory mechanism is shown. Further, the presented paper
      suggests that chemical and mechanical processes do not only facilitate or support
      one another but they may also play a triggering role for the other coupled
      process-some biochemical processes may need mechanical stimulation to run and
      vice versa as well-chemical reactions may provide energy for some mechanical
      processes. As an example, a detailed analysis of a model for controlled
      autocatalytic reproduction is presented, where the coupling effect, i.e. the
      influence of dynamic loading on reaction kinetics, is demonstrated.

PMID- 19863140
TI  - Structure of the alanine hydration shell as probed by NMR chemical shifts and
      indirect spin-spin coupling.
AB  - The structure of the alanine hydration shell was modeled by Carr-Parinello
      molecular dynamics (CPMD) to explain subtle differences in NMR chemical shifts
      and indirect spin-spin coupling constants of the neutral (zwitterionic),
      cationic, and anionic forms of this amino acid. In comparison with classical
      molecular dynamics (MD), the quantum mechanical CPMD approach revealed a more
      structured solvent and significant differences in the radial and angular
      distributions of the water molecules around the solute. In particular, the
      solvent was predicted to be organized around the uncharged COOH and NH(2)
      residues to a similar degree as that for the charged ones. This was not the case
      with MD. For snapshot CPMD configurations, the NMR parameters were computed by
      density functional theory (DFT) and averaged. Obtained values were significantly
      closer to experimental parameters known for (15)N and (13)C isotopically labeled
      alanine than those calculated by the conventional implicit dielectric solvent
      model. The NMR results also quantitatively reflect a superiority of the CPMD over
      the MD explicit solvent treatment. A further improvement of the computed spin
      spin coupling constants could be achieved by taking into account vibrational
      averaging beyond the harmonic approximation. Differently positioned water
      molecules in the clusters cause an unexpectedly large scattering of the NMR
      parameters. About 10-15 dynamics snapshots were required for a satisfactory
      convergence of the shifts and couplings. The NMR chemical shift was found to be
      much more sensitive to the molecular hydration than the coupling. The results
      thus indicate a large potential of the NMR spectroscopy and quantum simulations
      to probe not only the structure of molecules but also their interactions with the
      environment.

PMID- 19863141
TI  - Molecular dynamics simulations of the liquid surface of the ionic liquid 1-hexyl
      3-methylimidazolium bis(trifluoromethanesulfonyl)amide: structure and surface
      tension.
AB  - Molecular dynamics simulations of the liquid-vacuum interface of the ionic liquid
      1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide were performed with
      an all-atom force field. Structural properties of the interface, such as
      orientational ordering and density profiles, were calculated. The hexyl side
      chain of the cation is likely to protrude outward from the surface layer. There
      is a region with enhanced density from that of the bulk where the cation
      preferably slants with the imidazolium ring tending to be perpendicular to the
      interface. The surface tensions are calculated using mechanical and thermodynamic
      definitions via profiles along the direction normal to the interface. We also
      discuss the different contributions to the surface tension due to the repulsion
      dispersion and electrostatic interactions. The use of local pressure profiles
      provides an explanation to the systematic problems encountered by several
      researchers to obtain accurate values of the surface tension at low temperature.
      Even when macroscopically the system looks in equilibrium, locally this is not
      accomplished.

PMID- 19863142
TI  - Aromatic interactions in the binding of ligands to HMGCoA reductase.
AB  - 3-Hydroxy-3-methyglutaryl-coenzyme A (HMGCoA) reductase is the enzyme that
      catalyzes the rate-determining step in cholesterol synthesis; it is also the
      target for statin drugs, which are competitive inhibitors of the enzyme. We
      examine potentially important enzyme-ligand interactions currently not
      incorporated into statin drug design: weak, induction/dispersion interactions
      between ligands and residue tyrosine 479 in the HMGCoA reductase active site.
      HMGCoA is a large molecule with a long coenzyme A "tail", and in order to study
      the interactions of interest, it was necessary to find the smallest possible
      portion of the HMGCoA molecule that would serve as a reasonable model for the
      entire molecule. Using this minimal model, we calculated BSSE-corrected
      electronic interaction energies between the residue and the ligand molecule using
      several DFT methods (local, hybrid, and gradient-corrected DFT methods) as well
      as MP2. We also performed several in silico mutations of the tyrosine 479 residue
      to determine the potential effects of these changes on protein-ligand interaction
      energies. Our work shows that this previously unexploited protein-ligand
      interaction between tyrosine residue 479 and HMGCoA can be important in the
      design of future statin drugs. Per our previous work, our results show that local
      DFT methods more closely match MP2 energy values for aromatic binding than do
      hybrid or gradient-corrected DFT methods.

PMID- 19863143
TI  - Synthetic study toward the total synthesis of maoecrystal V.
AB  - A novel and concise approach for the construction of the core structure of
      maoecrystal V (1) has been developed. Utilizing the lead-mediated arylation of
      beta-ketoesters and oxidative dearomatization/IMDA reaction as key steps, the two
      consecutive all-carbon quaternary centers (C-9 and C-10) were constructed in a
      stereoselective manner. The developed chemistry paves the way for the total
      synthesis of this fascinating natural product.

PMID- 19863144
TI  - New terpenoids from the soft corals Sinularia capillosa and Nephthea chabroli.
AB  - Two new terpenoids, capillosanol (1) and chabranol (2), possessing unprecedented
      terpenoid skeletons, were isolated from the soft corals Sinularia capillosa and
      Nephthea chabroli, respectively. The structures of 1 and 2 were elucidated
      through extensive spectroscopic analyses. The cytotoxicities of these compounds
      were tested in vitro.

PMID- 19863145
TI  - Melohenines A and B, two unprecedented alkaloids from Melodinus henryi.
AB  - A phytochemical study on Melodinus henryi has led to the isolation of two novel
      alkaloids, melohenines A (1), a monoterpenoid indole alkaloid with additional
      skeletal carbons arranged compactly in eight rings, and melohenine B (2), an
      alkaloid with an unprecedented 6/9/6/6 tetracyclic ring system regarded as a key
      intermediate from indole to quinoline alkaloids. Their structures were elucidated
      by means of spectroscopic methods and further confirmed by X-ray diffraction
      analysis.

PMID- 19863146
TI  - Swerilactones C and D, anti-HBV new lactones from a traditional Chinese herb:
      Swertia mileensis.
AB  - Swerilactones C (1) and D (2), two novel diastereomeric lactones with an
      unprecedented 6/6/6/6/6 pentacyclic ring system, were isolated from the
      traditional Chinese herb Swertia mileensis. Their structures and relative
      stereochemistry were elucidated on the basis of spectroscopic methods and further
      confirmed by X-ray single-crystal diffraction analysis. In vitro antihepatitis B
      virus (HBV) assay on the Hep G 2.2.15 cell line showed that both compounds 1 and
      2 exhibited inhibitory activities against the secretion of HBsAg (IC(50) = 1.24
      and 2.96 mM, respectively) and HBeAg (IC(50) = 0.77 and 1.47 mM, respectively).

PMID- 19863147
TI  - Stereoselective synthesis of bicyclic tertiary alcohols with quaternary
      stereocenters via intramolecular crossed benzoin reactions catalyzed by N
      heterocyclic carbenes.
AB  - Bicyclic tertiary alcohols 1 bearing quaternary stereocenters at the two adjacent
      bridgehead positions were synthesized with high stereoselectivity via the
      intramolecular crossed benzoin reactions catalyzed by NHC organocatalysts.

PMID- 19863148
TI  - Benzosceptrins A and B with a unique benzocyclobutane skeleton and nagelamide S
      and T from Pacific sponges.
AB  - Four new dimeric pyrrole-2-aminoimidazole alkaloids have been isolated from the
      Pacific marine sponges Agelas cf. mauritiana and Phakellia sp. They include the
      unusual C2 symmetrical benzosceptrins A (4) and B (5), which each possess a
      unique benzocyclobutane skeleton and nagelamides S (6) and T (7). Their
      structures and relative configuration were elucidated from spectroscopic data.
      Plausible biogenetic paths for these compounds are also proposed in this paper.

PMID- 19863149
TI  - Stereocontrolled generation of the (2R) chroman core of vitamin E: total
      synthesis of (2R,4'RS,8'RS)-alpha-tocopherol.
AB  - (2R,4'RS,8'RS)-alpha-tocopherol (1) was prepared using, as the two key steps, a
      novel diastereoselective TiCl(4)-promoted (S)-sulfoxide-directed allylation of
      ketal 2 with allyl trimethyl silane 3 to efficiently generate the challenging
      (2R) stereocenter of the chroman moiety and a cross-metathesis reaction with
      olefin 4 to efficiently join the lipophilic alkyl chain present in the final
      target.

PMID- 19863150
TI  - Lewis acid catalyzed Diels-Alder reactions of 1,2-naphthoquinones.
AB  - The use of BF(3) x OEt(2) catalysis in Diels-Alder reactions of 3,4-unsubstituted
      1,2-naphthoquinones provides direct access to cis-tetrahydrophenanthrene
      derivatives in good to excellent yields (66-99%) without rapid adduct
      aromatization commonly associated with corresponding thermal processes.

PMID- 19863151
TI  - Neopentylglycolborylation of aryl chlorides catalyzed by the mixed ligand system
      NiCl2(dppp)/dppf.
AB  - The mixed ligand system 10 mol % NiCl(2)(dppp) with 5 mol % dppf was discovered
      to be an extremely efficient catalyst for the neopentylglycolborylation of a
      diversity of electron-rich and electron-deficient aryl chlorides. Optimization
      showed that 5 mol % catalyst with 10% dppf was even more efficient. These results
      highlight the complexity of the relationship between catalyst and coligand in Ni
      catalysis and the benefit of combinations of mixed ligand in catalyst design.

PMID- 19863152
TI  - Ytterbium(III) triflate catalyzed tandem Friedel-Crafts alkylation/hydroarylation
      of propargylic alcohols with phenols as an expedient route to indenols.
AB  - A method to prepare indenols efficiently by ytterbium(III) triflate catalyzed
      tandem Friedel-Crafts alkylation/hydroarylation of propargylic alcohols with
      phenols is described. The reaction was accomplished in moderate to excellent
      yields and regioselectivity under mild conditions and offers a straightforward
      and convenient one step synthetic route to bioactive indenols and its
      derivatives.

PMID- 19863153
TI  - (NHC)CuH-catalyzed entry to allenes via propargylic carbonate S(N)2'-reductions.
AB  - The copper hydride-catalyzed S(N)2'-reduction of propargylic carbonates provides
      an efficient route to functionalized allenes. The method takes advantage of the
      stabilizing effect of NHC ligands on CuH and combines high reactivity and
      stereoselectivity with excellent tolerance toward reactive functionalities.

PMID- 19863154
TI  - Selective synthesis of 1-functionalized-alkyl-1H-indazoles.
AB  - An efficient method for the selective "N1" alkylation of indazoles is described.
      Use of alpha-halo esters, lactones, ketones, amides, and bromoacetonitrile
      provides good to excellent yield of the desired N1 products.

PMID- 19863155
TI  - Platinum-catalyzed nucleophilic addition of vinylsilanes at the beta-position.
AB  - In the presence of catalytic amounts of PtCl(2) and metal iodides, beta
      substituted vinylsilanes reacted with aldehydes at the beta-position to give
      allyl silyl ethers. The Pt-catalyzed addition to aromatic aldehydes proceeded
      efficiently in the presence of LiI. The combined use of PtCl(2) and MnI(2) was
      found to be effective in addition to aliphatic aldehydes.

PMID- 19863157
TI  - pH-Dependent configurations of a 5-chlorouracil-guanine base pair.
AB  - Hypochlorous acid (HOCl) from activated neutrophils at sites of inflammation can
      react with and damage biological molecules, including nucleic acids. The reaction
      of HOCl with cytosine analogues can generate multiple products, including 5
      chlorouracil (ClU). In this paper, we have constructed oligonucleotides
      containing ClU paired opposite guanine (ClU-G). Melting studies indicate that
      oligonucleotide duplexes containing the ClU-G mispair are substantially less
      stable than those containing a ClU-A base pair. The melting temperature of the
      ClU-G mispair is not experimentally distinguishable from that of a T-G pair. NMR
      studies indicate that the ClU-G base pair adopts a wobble geometry at neutral pH,
      similar to a T-G mispair. The exchangeable protons of the ClU-G mispair broaden
      rapidly with an increase in temperature, indicating that the ClU-G mispair is
      less stable and opens more easily than the surrounding adjacent base pairs.
      Unlike the ClU-A base pair studied previously [Theruvathu, J. A., et al. (2009)
      Biochemistry 48, 7539-7546], the ClU-G mispair undergoes a pH-dependent
      structural change, assuming an ionized base pair configuration that approximates
      a Watson-Crick base pair at higher pH. Ionization of ClU in a DNA template could
      promote mispair formation and mutation, in accord with previous studies on other
      5-halouracil analogues. The electron-withdrawing 5-chloro substituent facilitates
      ionization of the ClU N3 proton, promoting mispair formation, but it also renders
      the glycosidic bond susceptible to base cleavage by DNA repair glycosylases.

PMID- 19863156
TI  - Distinct pose of discodermolide in taxol binding pocket drives a complementary
      mode of microtubule stabilization.
AB  - The microtubule cytoskeleton has proven to be an effective target for cancer
      therapeutics. One class of drugs, known as microtubule stabilizing agents (MSAs),
      binds to microtubule polymers and stabilizes them against depolymerization. The
      prototype of this group of drugs, Taxol, is an effective chemotherapeutic agent
      used extensively in the treatment of human ovarian, breast, and lung carcinomas.
      Although electron crystallography and photoaffinity labeling experiments
      determined that the binding site for Taxol is in a hydrophobic pocket in beta
      tubulin, little was known about the effects of this drug on the conformation of
      the entire microtubule. A recent study from our laboratory utilizing hydrogen
      deuterium exchange (HDX) in concert with various mass spectrometry (MS)
      techniques has provided new information on the structure of microtubules upon
      Taxol binding. In the current study we apply this technique to determine the
      binding mode and the conformational effects on chicken erythrocyte tubulin (CET)
      of another MSA, discodermolide, whose synthetic analogues may have potential use
      in the clinic. We confirmed that, like Taxol, discodermolide binds to the taxane
      binding pocket in beta-tubulin. However, as opposed to Taxol, which has major
      interactions with the M-loop, discodermolide orients itself away from this loop
      and toward the N-terminal H1-S2 loop. Additionally, discodermolide stabilizes
      microtubules mainly via its effects on interdimer contacts, specifically on the
      alpha-tubulin side, and to a lesser extent on interprotofilament contacts between
      adjacent beta-tubulin subunits. Also, our results indicate complementary
      stabilizing effects of Taxol and discodermolide on the microtubules, which may
      explain the synergy observed between the two drugs in vivo.

PMID- 19863158
TI  - WITHDRAWN.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 19863159
TI  - Renal infection by a new coccidian genus in big brown bats (Eptesicus fuscus).
AB  - A novel coccidian parasite from the kidney of big brown bats (Eptesicus fuscus)
      is described. This coccidian (Nephroisospora eptesici nov. gen., n. sp.) was
      associated with a generally mild, focal or multifocal, well-demarcated cortical
      renal lesion less than 1 mm in diameter. The lesion represented cystic, dilated
      tubules with hypertrophied tubular epithelial cells and was present in the
      kidneys of 29 of 590 bats. Numerous coccidian parasites in various stages of
      development were present within the tubular epithelial cells and within the cyst
      lumina. Oocysts were collected from cystic dilated tubules. Thin-walled,
      sporulated ellipsoidal oocysts measuring an average of 18.9 x 20.8 microm were
      present in kidney tissue. The oocysts contained 2 sporocysts with 4 sporozoites.
      A polar body and a prominent oocyst residuum were present in the oocysts, but no
      micropyle, sporocyst residuum, or Stieda bodies were detected. Analysis of the
      18S rRNA gene sequence put the parasite in the Sarcocystidae. The parasite is
      closely related to Besnoitia, Hammondia, Neospora, and Toxoplasma.
      Ultrastructural features, such as the presence of an apical complex in
      merozoites, support the identification of a coccidian. A new genus and species,
      Nephroisospora eptesicii, is proposed for this unusual coccidian in which the
      entire cycle is completed in the kidney of a single host; it has a membrane-like
      oocyst wall, sporogony occurs in the host rather than in the abiotic environment,
      and the positioning of the parasite by nucleic acid sequence indicates it to be
      closely allied to Sarcocystis and Besnoitia.

PMID- 19863160
TI  - Effect of preparation technique on the properties and in vivo efficacy of
      benzocaine-loaded ethosomes.
AB  - This study aimed to investigate the influence of the preparation conditions on
      the performance of an ethosomal formulation for topical delivery of the local
      anesthetic agent, benzocaine (BZC). Ethosomes were prepared with different
      techniques, such as thin-layer evaporation, freezing and thawing, reverse-phase
      evaporation, extrusion and sonication, obtaining, respectively, multilayer
      vesicles (MLVs), frozen and thawed MLV (FATMLV), large unilamellar vesicles
      (LUVs), and small unilamellar vesicles (SUVs). The obtained vesicles were
      characterized for morphology, size, zeta potential, and entrapment efficiency
      (EE%), and their stability was monitored during storage at 4 degrees C. In vitro
      permeation properties from gels incorporating drug ethosomal dispersions were
      evaluated in vitro by using artificial lipophilic membranes, while their
      anesthetic effect was determined in vivo on rabbits. The results suggested that
      the vesicle preparation method plays an important role in affecting the
      properties and effectiveness of ethosomal formulations. MLVs and LUVs exhibited
      higher drug EE% and better stability than FATMLV and SUV vesicles. The In vitro
      drug permeation rate was directly related to the vesicle EE% and varied in the
      order MLV>LUV approximately FATMLV>SUV. The therapeutic efficacy of BZC ethosomal
      formulations was significantly improved with respect to the corresponding BZC
      solution. The best results, in terms of enhanced intensity of anesthetic effect,
      were given by formulations containing MLVs and LUVs, and the order of
      effectiveness was MLV approximately LUV>FATMLV approximately SUV, rather similar
      to that found in permeation studies. On the contrary, unexpectedly, the
      effectiveness order in increasing the duration of drug action was SUV> or
      =MLV>LUV approximately FATMLV. The highest efficacy of SUVs was probably due to
      the more intimate contact with the epithelium due to their greatest surface area,
      which allowed the longest extension of drug therapeutic action. The overall
      results suggest that a suitably developed ethosomal formulation of BZC can be of
      actual value for improving its clinical effectiveness in topical anesthesia.

PMID- 19863161
TI  - A phase I clinical and pharmacokinetic study (LIPOTEC - GP PHARM/DOXO 01) of a
      new liposomal doxorubicin given as 3-week schedule in patients with solid tumors.
AB  - As a dose-finding phase I study of a new liposomal formulation of doxorubicin
      (LipD), patients (n = 39; median age: 60 years; range, 41-75; median ECOG
      performance status, 1; range, 0-2) with refractory cancer had a starting dose of
      LipD administered at 30 mg/m(2) as a 1-hour intravenous infusion. Cycle duration
      was 21 days. At the recommended dose (RD), patients received a first cycle of
      nonliposomal doxorubicin (non-LipD) to evaluate intrapatient pharmacokinetic
      differences between non-LipD and LipD. The most frequent diagnosis was head and
      neck tumor (7 patients). Tolerance and safety of dose levels of 30, 40, 50, 60,
      70, 80, and 90 mg/m(2) were evaluated. A total of 131 cycles were administered
      (median per patient, 3; range, 1-6). Of the 39 patients, 8 completed the planned
      six cycles. Febrile neutropenia was dose limiting and defined the toxic dose of
      LipD as 70 mg/m(2). Other significant toxicities included asthenia (G2: 31%; G3:
      8%), neutropenia (G3: 35%; G4: 29%), thrombopenia (G3: 15%; G4: 2%), anemia (G1
      G2: 67%; G3-G4: 5%), mucositis (G1-G2: 32%, G3: 4%), and acute allergic reactions
      (G1-G2: 36%). Comparison of pharmacokinetic profiles of non-LipD and LipD showed
      that higher exposure was achieved with LipD. Stable disease was observed in 14
      patients. We conclude that the LipD regimen, given as a 1-hour infusion every 3
      weeks, is well tolerated and has a favorable pharmacokinetic profile. The
      recommended dose is 70 mg/m(2) with prophylactic antihistamines and corticoids to
      preempt allergic reaction.

PMID- 19863162
TI  - Phosphatidyl choline-based colloidal systems for dermal and transdermal drug
      delivery.
AB  - In this study we have prepared various phosphatidyl choline based colloidal
      systems, namely liposomes, transfersomes, microemulsions and micelles, using
      similar excipients and compared their ability to deliver drugs into and through
      the skin under occlusive and non-occlusive conditions. Hydrophilic propranolol
      hydrochloride (PHCl) and lipophilic propranolol base (PB) were used as model
      drugs. All tested parameters, that is formulation composition, drug
      characteristics and testing conditions, influenced skin permeability and skin
      retention. A trend was observed showing that the skin permeation as well as skin
      retention decreases with the amount of phosphatidyl choline in the formulations
      for both tested model drugs (micelles > transfersomes > liposomes >
      microemulsion). The lipophilic model drug had higher skin permeability especially
      when incorporated into the systems containing mainly hydrophilic excipients. Skin
      retention, however, was not affected by the drug hydrophilicity to the same
      extent as skin permeability. Occlusion increased both skin retention and skin
      permeation for both model drugs.

PMID- 19863163
TI  - The tissue distribution in mice and pharmacokinetics in rabbits of oxaliplatin
      liposome.
AB  - A rapid, sensitive, and simple high-performance liquid chromatographic (HPLC)
      method with an ultraviolet detector (UV) has been developed for the determination
      of oxaliplatin in the plasma of rabbits and tissues of mice. The sample
      preparation was carried out by complexation with 0.5 mL of DETC (diethyl
      dithiocarbamate) solution and extracted by ether and chloroform. Then, 20 microL
      of supernatant was injected into the HPLC system with 0.25 mol/L of sodium
      chloride solution and methanol (30:70 v/v) as the mobile phase at a flow rate of
      1.0 mL/min. Separation was performed with a C(18) column at 25 degrees C. The
      peak was detected at 254 nm. The calibration curve was linear (R(2) > or =
      0.9995) in the concentration range of 0.1 approximately 200 microg/mL in plasma
      and tissues. The intra- and interday variation coefficients were not more than
      2.61 and 3.83%, respectively. The limit of detection was 20 ng/mL. The mean
      recoveries of oxaliplatin were ranged from 97.83 to 104.17% in plasma and
      tissues. The present method has been successfully applied to the pharmacokinetic
      study of oxaliplatin liposome in mice and rabbits.

PMID- 19863164
TI  - Formulation and evaluation of ATP-containing liposomes including lactosylated
      ASGPr ligand.
AB  - An original ligand (Lac-10-Chol) designed to interact with asialoglycoprotein
      receptors to potentially target hepatocyte was synthesised by grafting a lactose
      head to a cholesteryl structure, which was then included in liposomes.
      Preliminary formulation tests led to the selection of conventional formulations
      based on soybean phosphatidylcholine/cholesterol/DOTAP (+/- DOPE) (+/- Lac-10
      Chol) that present reproducible absolute entrapment value (1.45 +/- 0.10%), with
      a size of 109 +/- 7 nm and a slight positive charge (3.77 +/- 1.59 mV). Cell
      viability (via the MTT test), expressed as the percentage of nontreated cells in
      HepG2 cells, was very close to the control. Internalization tests evidenced an
      intracellular penetration of fluorescent liposomes, but no specific ligand effect
      was demonstrated (P > 0.05). Nevertheless, regarding the adenosine triphosphate
      (ATP) assay, a slight increase was obtained with liposome loaded with ATP
      incorporating Lac-10-chol after 24 hours (P < 0.05).

PMID- 19863165
TI  - Virosomes can enter cells by non-phagocytic mechanisms.
AB  - Phagocytosis of fine particles (1 microm) by macrophages is a ligand-receptor
      mediated, actin-based process, whereas the entering of smaller particles (< or =
      0.2 microm) in macrophages occurs also by other mechanisms. Virosomes with a
      diameter of 0.12-0.18 microm are widely used as carrier systems for drugs,
      vectors, and plasmids in cancer therapy or for vaccines. We investigated their
      interactions with airway cells, in particular penetration into monocyte-derived
      macrophages. The microscopic analysis of phagocytic cells incubated with
      virosomes and polystyrene particles showed that virosomes and particles
      penetrated cells even in the presence of cytochalasin D, a drug inhibiting actin
      based phagocytosis. The charge of the virosomes and particles did not influence
      their penetration. Also, different inhibitors of endocytotic pathways did not
      prevent the particles and virosomes from penetrating into the cells.
      Additionally, to study the ability of virosomes to overcome the epithelial airway
      barrier, a triple cell co-culture model composed of epithelial cells, monocyte
      derived macrophages and dendritic cells of the respiratory tract was used. We
      found virosomes and polystyrene particles in both populations of antigen
      presenting cells, monocyte-derived macrophages, and dendritic cells, in the
      latter even if they were not directly exposed. In conclusion, virosomes are
      readily taken up by monocyte-derived macrophages, both by conventional
      phagocytosis and by actin-independent mechanisms. Further, they can penetrate the
      airway barrier and reach resident dendritic cells. Therefore, virosomes are
      promising vaccine candidates.

PMID- 19863166
TI  - Role of nanocarrier systems in cancer nanotherapy.
AB  - Cancer continues to be a major cause of morbidity and mortality worldwide. While
      discovery of new drugs and cancer chemotherapy opened a new era for the treatment
      of tumors, optimized concentration of drug at the target site is only possible at
      the expense of severe side effects. Nanoscale carrier systems have the potential
      to limit drug toxicity and achieve tumor localization. When linked with tumor
      targeting moieties, such as tumor-specific ligands or monoclonal antibodies, the
      nanocarriers can be used to target cancer-specific receptors, tumor antigens, and
      tumor vasculatures with high affinity and precision. This article is an overview
      of advances and prospects in the applications of nanocarrier technology in cancer
      therapy. Applications of nanoliposomes, dendrimers, and nanoparticles in cancer
      therapy are explained, along with their preparation methods and targeting
      strategies.

PMID- 19863167
TI  - Development and characterization of liposomal formulations for rapamycin delivery
      and investigation of their antiproliferative effect on MCF7 cells.
AB  - Rapamycin (Sirolimus) is a macrolide lactone with antifungal, immunosuppressant,
      and antiproliferative actions. The mechanism of rapamycin action involves the
      inhibition of mTOR and subsequent cytostasis. Rapamycin also prevents
      angiogenesis in tumors and can prevent cancer cells' resistance to other
      chemotherapeutic agents. However, very poor water solubility, bioavailability,
      only slight solubility in acceptable parenteral excipients, chemical instability,
      and major sequestration (95%) of free rapamycin into the erythrocytes have
      prevented its development as an anticancer drug. To address these problems, it
      was attempted to develop liposomal rapamycin delivery systems in this study.
      Conventional and pegylated liposomes were prepared with various lipid and
      cholesterol ratios. They were then characterized; these liposomes contained 0.68
      0.90 mg of rapamycin per milliliter of liposome suspension. Having suitable
      particle size, these liposomes successfully retained the entrapped drug. Both
      types of liposomes were found to be effective; however, conventional liposomes
      showed better antiproliferative activity against MCF-7 cells than pegylated
      liposomes. But, pegylated liposome showed better stability than conventional
      liposomes. In conclusion, the enhanced permeability and retention effects of
      tumors should provide the opportunity for pegylated liposomal rapamycin to be
      applied as an intravenous drug-delivery system for targeted delivery to cancer
      cells, avoiding the major sequestration of free rapamycin into the erythrocytes.

PMID- 19863168
TI  - Span and Tween neutral and pH-sensitive vesicles: characterization and in vitro
      skin permeation.
AB  - The aim of this work was the preparation, characterization, and comparison of
      novel pH-sensitive nonphospholipid vesicles (niosomes) from two nonionic
      surfactants, with different hydrophilic-lipophilic balance values (Tween20-TW20 =
      16.7 and Span60-SP60 = 4.7). Surfactants were mixed with cholesterol (CHOL) and
      its derivative, cholesteryl hemisuccinate (CHEMS), as a pH-sensitive molecule.
      Vesicles were characterized by dynamic light scattering, in order to evaluate
      their dimensions and vesicle stability, by zeta-potential measurements and by
      means of electronic microscopy after freeze-fracture. Ibuprofen (IBU) was used as
      the model drug, and high-performance liquid chromatography analyses were
      performed to evaluate drug-entrapment efficiency and release in a neutral, acidic
      environment. The influence of the vesicle composition on skin accumulation and
      transdermal permeation of IBU across excised hairless rat skin was investigated
      by using vertical Gummer diffusion cells. When niosomes with SP60 and CHEMS were
      prepared, there was a statistically significant increase of skin permeation of
      IBU, while TW20 niosomes did not show statistically significant differences in
      P(app) values without the influence of the vesicle size and charge.

PMID- 19863169
TI  - Elevated plasma levels of the angiogenic tetrapeptide acetyl-ser-asp-lys-pro are
      found in some patients with hematologic malignancies.

PMID- 19863170
TI  - MHC class II as a therapeutic target in B-cell lymphomas: the CIITA road to
      paradise?

PMID- 19863171
TI  - Interim positron emission tomography scan in multi-center studies: optimization
      of visual and quantitative assessments.
AB  - 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is being used much
      more for response monitoring in multi-center studies. By visual assessment,
      positron emission tomography (PET) will be scored as negative or positive
      according to the abnormal 18F-fluorodeoxyglucose (FDG) uptake at previously
      involved sites. However, a gray-zone does exist especially in interim-PET scans.
      Besides visual inspection, semi-quantitative analyses using standardized uptake
      values (SUVs) allow for an objective assessment of treatment response, thereby
      eliminating observer variation and providing the opportunity to reduce the gray
      zone by adding the quantitative power of PET. However, comparison of SUV results
      is often hampered by the wide variability in methodology of data acquisition,
      image reconstruction, and data analysis procedures. In the Netherlands, a
      protocol for standardization and quantification of FDG-PET whole body studies has
      been defined for the accurate use of SUVs in FDG-PET multi-center studies. Here,
      we report a summary of the main issues.

PMID- 19863172
TI  - Thyroid function and its clinical significance in POEMS syndrome.
AB  - POEMS syndrome, also known as Crow-Fukase syndrome, represents a rare multisystem
      syndrome characterized by polyneuropathy, organomegaly, endocrinopathy, M
      protein, and skin changes. Hypothyroidism is one of the common endocrine
      abnormalities which are central features of POEMS syndrome. The clinical data
      associated with the measurement of thyroid function and its clinical significance
      in POEMS syndrome is still rare. Herein, we report 24 cases with POEMS syndrome
      which were studied thyroid function and clinical manifestations and performed an
      associated analysis between hypothyroidism and edema/effusions. Of the 24
      patients with POEMS syndrome, 17(70.8%) had a recognized hypothyroidism
      (including 11 clinical hypothyroidism and 6 subclinical hypothyroidism). Fourteen
      patients (58.3%) had some form of extravascular volume overload. In 14 patients
      with edema/effusions, 12 were diagnosed as having hypothyroidism. Hypothyroidism
      may be one of causes of edema/effusions. After thyroid hormone treatment and
      chemotherapy, symptoms of hypothyroidism and edema /effusions were improved
      greatly.

PMID- 19863173
TI  - Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and
      prednisolone therapy has a high risk of developing interstitial pneumonia in
      patients with non-Hodgkin lymphoma.
AB  - There are a few reports suggesting that rituximab (RTX) might be a risk for
      interstitial pneumonitis (IP). We also experienced such patients in the era of
      RTX. Here, we reviewed all the patients with non-Hodgkin lymphoma who were
      treated with RTX-CHOP-like regimen (R-CHOP) to determine the risk of developing
      IP. One of 59 (1.7%) patients who received CHOP alone and 8 of 129 (6.2%)
      patients who were treated with R-CHOP experienced IP (p = 0.28). Furthermore,
      three of eight patients who have had IP during R-CHOP were confirmed having
      Pneumocystis jirovecii pneumonia (PCP). PCP occurred during the fourth, sixth,
      and seventh cycle of chemotherapy, respectively. Among the patients treated by R
      CHOP, 3 of 32 (9%) patients whose lymphocyte counts were <1000/microL before
      chemotherapy developed PCP, while 70 patients whose lymphocyte counts were
      >1000/microL did not (p = 0.03). In four of eight patients, IP occurred during
      the administration of granulocyte-colony stimulating factor. RTX seems to have a
      certain risk to induce IP including PCP. Patients with lymphoma who were treated
      by R-CHOP regimen, might be considered as PCP prophylactic, especially if the
      number of lymphocytes is low at the beginning of chemotherapy.

PMID- 19863174
TI  - IgA nephropathy associated with cutaneous T cell lymphoma.

PMID- 19863175
TI  - De novo CD5+ diffuse large B-cell lymphoma: a distinct subset with adverse
      features, poor failure-free survival and outcome with conventional therapy.

PMID- 19863176
TI  - Pediatric nodal marginal zone lymphoma may develop in the adult population.
AB  - Pediatric nodal marginal zone lymphoma (NMZL) is described as a separate variant
      of NMZL in the most recent WHO classification of tumors of hematologic and
      lymphoid tissues. It has distinctive morphology and clinical presentation and
      stands out as an indolent disease with remarkably better overall prognosis
      compared to classic NMZL. Here we report two adult patients with NMZL with
      clinical and morphologic features consistent with pediatric NMZL (pNMZL) and
      review available literature describing the clinical and histologic presentation
      of pNMZL. Two men, ages 44 and 18 years, each presented with localized cervical
      lymphadenopathy, both demonstrated florid proliferation of the marginal zone and
      disruption of reactive germinal centers, progressive transformation of germinal
      centers-like morphologic features typical for pNMZL and clonal disease with
      immunophenotype consistent with NMZL. This is the first report of pNMZL in a
      middle-aged person. Distinct histologic features and characteristic benign
      clinical course will help to distinguish this rare variant from other NMZL in the
      adults. Clinically, recognition is important to understand the true incidence of
      this rare form in the adult population and to avoid unnecessary overtreatment of
      this indolent form.

PMID- 19863177
TI  - Positron emission tomography guided therapy of aggressive non-Hodgkin lymphomas-
      the PETAL trial.
AB  - In aggressive non-Hodgkin lymphomas, the result of positron emission tomography
      (PET) with [18F]fluorodeoxyglucose performed after a few cycles of chemotherapy
      has been shown to correlate with long-term treatment outcome. The PETAL trial
      investigates whether a change in treatment protocol may improve the outcome of
      patients with a positive scan after two cycles of (R-)CHOP. Such patients are
      randomized to receive a further six cycles of (R-)CHOP or six blocks of the B-ALL
      protocol, a regimen for the treatment of Burkitt lymphoma. Precautions taken to
      minimize false-positive interim-PET results include adherence to a 3-week
      interval between chemotherapy and interim-PET scanning, avoidance of
      hematopoietic growth factors, and SUV-based rather than visual interim-PET
      assessment. So far, 175 patients have been enrolled of whom 128 have reached
      interim-PET scanning. In patients with a positive scan, relapses were six times
      more frequent than in patients with a negative scan. Recruitment into the trial
      continues.

PMID- 19863178
TI  - Interim 18F-fluorodeoxyglucose positron emission tomography in diffuse large B
      cell lymphoma: qualitative or quantitative interpretation--where do we stand?
AB  - Interim 18F-fluorodeoxyglucose positron emission tomography performed early
      during the course of therapy in diffuse large B-cell lymphoma is highly
      predictive of outcome and now used in many clinical trials to validate risk
      adapted strategies. However, interpretation criteria of interim PET are not yet
      appropriately defined for the evaluation of tumor response and chemosensitivity.
      From the results of our studies, a quantitative approach based on SUV(max)
      reduction between baseline PET (PET0) and interim PET demonstrated a higher
      predictive value than visual analysis when PET was performed at two cycles (PET2)
      but was equivalent to visual analysis at four cycles (PET4). The SUV(max)
      reduction index at PET2 seems to be the best predictor of the response compared
      to clinical or molecular prognostic indices. When visual analysis is necessary,
      the use of an online independent reading network may solve the interobserver
      variability, but the hurdles of visual analysis deserve an international
      validation study to confirm the newly proposed criteria.

PMID- 19863179
TI  - Current clinical evidence on interim fluorine-18 fluorodeoxy glucose positron
      emission tomography for advanced-stage Hodgkin lymphoma and diffuse large B-cell
      lymphoma to predict treatment outcomes.
AB  - We assessed the quality of current evidence on fluorine-18 fluorodeoxy glucose
      positron emission tomography (FDG-PET) performed after a few cycles of
      chemotherapy for patients with advanced-stage Hodgkin lymphoma (HL) or diffuse
      large B-cell lymphoma (DLBCL) based on a recently published systematic review of
      the literature. There is a moderate level of evidence suggesting that interim PET
      has an excellent prognostic ability to predict treatment failures in low- to
      intermediate-risk advanced-stage HL patients. Evidence is insufficient for DLBCL
      due to the clinical heterogeneity of the primary studies. Interim PET should at
      present not be regarded as an established procedure and it still remains as an
      unproven test for routine clinical practice. Its use should currently be reserved
      for research studies where treatment strategies and imaging protocols are
      standardized.

PMID- 19863180
TI  - Mantle cell lymphoma: state-of-the-art management and future perspective.
AB  - Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphomas
      (NHL) characterized in almost all cases by the chromosomal translocation
      t(11;14)(q13;q32) and nuclear cyclin D1 overexpression. Most patients present
      with advanced stage disease, often with extranodal dissemination, and typically
      pursue an aggressive clinical course. Recent improvement has been achieved by the
      successful introduction of monoclonal antibodies and dose-intensified approaches
      including autologous stem cell transplantation strategies. However, with the
      exception of allogeneic hematopoietic stem cell transplantation, current
      treatment approaches are not curative and the corresponding survival curve is
      characterized by a relatively steep and continuous decline, with a median
      survival of about 4 years and <15% long-term survivors. Despite its rarity, MCL
      is of particular clinical and scientific interest by providing a paradigm for
      neoplasms with dysregulated control of cell cycle machinery and impaired
      apoptotic pathways. Recently gained insights into underlying pathobiology unravel
      numerous promising molecular targeting strategies, however their introduction
      into clinical practice and current treatment algorithms remains a challenge. This
      article will provide relevant information for decision making in clinical
      practice and give a perspective on upcoming management strategies.

PMID- 19863181
TI  - Variation in WNT genes expression in different subtypes of chronic lymphocytic
      leukemia.
AB  - The Wnt molecules are a family of secretory glycoproteins implicated in
      proliferation and differentiation of both normal and malignant cells. Despite
      extensive investigation of the WNT genes expression profile in various tumors,
      little is known about their expression in chronic lymphocytic leukemia (CLL). In
      this study, the expression profile of 14 WNT genes was investigated in a large
      number of Iranian patients with CLL. Semi-quantitative RT-PCR was performed on
      peripheral blood leukemic cells obtained from 62 patients with CLL. Peripheral
      blood mononuclear cells isolated from 11 age matched normal subjects served as
      control to determine baseline expression level of these genes. Our results have
      demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A,
      WNT-10A, and WNT-16B in patients with CLL compared to normal subjects (p < 0.05
      to p < 0.0001). WNT gene expression analysis in different CLL subtypes showed a
      similar pattern of expression in progressive and indolent clinical subtypes. Over
      expression of WNT-5A and WNT-9A genes was observed in patients with no mutation
      in their immunoglobulin (Ig) variable region heavy chain (Ig VH) genes compared
      to those with mutated Ig VH genes. Comparison between patients expressing VH1 (n
      = 9), VH3 (n = 40) and VH4 (n = 12) gene families, revealed down-regulation of
      WNT-3 and WNT-9A in VH3 positive patients. Our results indicate up-regulation of
      many members of the WNT gene family in CLL suggesting involvement of the Wnt
      canonical and/or noncanonical signaling pathways in CLL tumorigenesis.

PMID- 19863182
TI  - DNA damage in horticultural farmers: a pilot study showing an association with
      organophosphate pesticide exposure.
AB  - A study of horticultural farmers exposed to organophosphate pesticides (OPs) and
      controls investigated the relationships between OP exposure, DNA damage and
      oxidative stress. Blood acetylcholinesterase (AChE) and urinary dialkylphosphate
      (DAP) levels determined exposure and 8-hydroxy-29- deoxyguanosine (8OHdG)
      indicated oxidative stress status. The farmers had approximately 30% lower AChE
      activity and increased DAP levels compared with the controls, reflecting moderate
      OP exposure. They had higher DNA damage than the controls and there was a
      significant positive relationship between DAP and DNA damage with greater than
      95% power. The farmers also had a significant positive relationship between
      urinary DAP and 8OHdG levels.

PMID- 19863183
TI  - Two novel non-destructive biomarkers to assess PAH-induced oxidative stress and
      porphyrinogenic effects in crabs.
AB  - Two novel, non-destructive assays were developed to evaluate contaminant-induced
      lipid peroxidation (thiobarbituric acid-reacting substances, TBARS, levels) and
      haem biosynthesis disruption (porphyrin excretion) in decapod crabs. A laboratory
      experiment was conducted whereby pie-crust crabs (Cancer novaezelandiae) were fed
      cockles (Austrovenus stutchburyi) collected from a contaminated and reference
      site and TBARS levels and porphyrin excretion determined using fluorometric
      analysis in urine samples. Pyrene metabolite levels were also measured in the
      same urine samples to assess polycyclic aromatic hydrocarbon (PAH) exposure.
      Contaminant-exposed crabs exhibited elevated urinary TBARS and porphyrin levels
      and a strong correlation was found between these two assays and the urinary
      pyrene metabolite concentrations. However, there was large within-treatment
      variability, which precluded a clear separation between the control and the
      impacted group. Nevertheless, consistency in the direction of the response shows
      that the biomarkers reflect pollutant levels and validates the use of these
      simple techniques from human medicine for environmental assessments.

PMID- 19863184
TI  - Assessment of oxidative stress in coronary artery bypass surgery: comparison
      between the global index OXY-SCORE and individual biomarkers.
AB  - The performances of the OXY-SCORE, a summary index of oxidative stress, and of
      its individual components (plasma malondialdehyde (MDA), oxidized and reduced
      glutathione, individual antioxidant capacity, alpha- and gamma-tocopherol and
      urinary isoprostanes) were assessed in 47 patients undergoing coronary surgery,
      randomly assigned to cardiopulmonary bypass (CPB) or off-pump procedure (OPCAB)
      associated with less oxidative stress. The ability of the OXY-SCORE to classify
      correctly the patients was high (area under the ROC curve 0.90). Only free MDA
      showed a similar performance, but it was insensitive to the minor variations of
      the oxidative balance in the OPCAB group.

PMID- 19863185
TI  - CR3 (CD11b/CD18) activation of nasal neutrophils: a measure of upper airway
      endotoxin exposure.
AB  - Inhaled endotoxin (lipopolysaccharide, LPS) initiates an inflammatory response
      and leads to the expression of CR3 (CD11b/CD18) receptors on polymorphonuclear
      leukocytes (PMNs). We determined if PMN activation in nasal lavage fluid (NLF) is
      a possible biomarker of occupational endotoxin exposure. Seven subjects exposed
      to endotoxin provided NLF samples that were split into three aliquots (negative
      control--1 M nicotinamide; sham; positive control--11 etag of exogenous LPS) and
      PMN activation was measured using a chemiluminometer. Differences in mean PMN
      activation were apparent, negative control: 548 +/- 15.65 RLU 100 microl(-1);
      sham: 11469 +/- 2582 RLU 100 microl(-1); positive control: 42026 +/- 16659 RLU
      100 microl (n = 7; p <0.05). This technique shows promise as a diagnostic method
      for measuring upper airway LPS exposure.

PMID- 19863186
TI  - CYFRA21-1 and CEA are useful markers for predicting the sensitivity to
      chemoradiotherapy of esophageal squamous cell carcinoma.
AB  - BACKGROUND: Chemoradiotherapy (CRT) is currently performed for patients with
      advanced esophageal carcinoma. Sensitivity of tumours to CRT differs from one
      case to another and may be influenced by the expression of biological molecules.
      The aim of this study was to identify biological markers which could predict
      sensitivities of esophageal squamous cell carcinoma (ESCC) to CRT. METHODS: A
      total of 84 patients with stage I-IV ESCC were evaluated. The cytokeratin 19
      fragment antigen 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) levels were
      measured before CRT by enzyme-linked immunosorbent assays in patients with
      primary ESCCs using 3.4 ng ml(-1) and 3.3 ng ml(-1), respectively, as cut-off
      values. The relationships between pretreatment expression of CYFRA 21-1 and CEA
      and the effectiveness of CRT were analysed. RESULTS: The complete response (CR)
      rates of the primary tumours estimated by computed tomography in patients with
      high levels of CYFRA21-1 and CEA were 10% (3/30) and 4.2% (1/24), while in cases
      with low CYFRA21-1 and CEA the CR rates were 50% (27/54) and 48.3% (29/60),
      respectively (p = 0.002 and 0.003). The effective rates (CR+PR) in CYFRA21-1 high
      and low groups were 60% (18/30) and 96.3% (52/54), while in CEA high and low
      groups they were 58.3% (14/24) and 93.3% (56/60), respectively (p = 0.013 and
      0.013). CONCLUSION: CYFRA21-1 and CEA may be helpful in predicting the
      responsiveness in ESCC of primary lesions to CRT, although the results should be
      confirmed in larger, more homogeneous studies.

PMID- 19863187
TI  - Cultured human cells release soluble gamma-glutamyltransferase complexes
      corresponding to the plasma b-GGT.
AB  - Serum gamma-glutamyltransferase (GGT) is thought to derive from the liver, but
      its values predict morbidity and mortality for several diseases, such as cardiac
      infarction, stroke, diabetes, renal failure and cancer. We assessed total GGT and
      its fractions in the culture supernatants of human cell lines (melanoma, prostate
      cancer, bronchial epithelium) by gel filtration chromatography. We also compared
      the GGT elution profile in plasma and the corresponding very-low-density
      lipoprotein (VLDL) fraction. All the cell lines tested released soluble GGT whose
      activity increased in parallel with the cell growth. Released GGT presented a
      molecular weight of 2000 kDa, identical to the b-GGT fraction of human plasma and
      corresponding to that of VLDL. But ultracentrifugation studies showed that b-GGT
      had a higher density than VLDL. The b-GGT present in human plasma can be produced
      by tissues other than the liver, thus explaining the increase of serum GGT
      observed in diseases of other organs.

PMID- 19863188
TI  - Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer's
      disease.
AB  - The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein
      biomarkers in neuropathologically confirmed Alzheimer's disease (AD), non
      demented (ND) elderly controls and non-AD dementias (NADD) was assessed.
      Candidate markers were selected on the basis of initial two-dimensional gel
      electrophoresis studies or by literature review. Markers selected by the former
      method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR)
      and pigment epithelium-derived factor (PEDF), while markers identified from the
      literature included Abeta1-40, Abeta1-42, total tau, phosphorylated tau, alpha-1
      acid glycoprotein (A1GP), haptoglobin, zinc alpha-2 glycoprotein (Z2GP) and
      apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were
      measured by enzyme-linked immunosorbent assay (ELISA). The concentrations of
      Abeta1-42, ApoA1, A1GP, ApoE, HPX and Z2GP differed significantly among AD, ND
      and NADD subjects. Logistic regression analysis for the diagnostic discrimination
      of AD from ND found that Abeta1-42, ApoA1 and HPX each had significant and
      independent associations with diagnosis. The CSF concentrations of these three
      markers distinguished AD from ND subjects with 84% sensitivity and 72%
      specificity, with 78% of subjects correctly classified. By comparison, using
      Abeta1-42 alone gave 79% sensitivity and 61% specificity, with 68% of subjects
      correctly classified. For the diagnostic discrimination of AD from NADD, only the
      concentration of Abeta1-42 was significantly related to diagnosis, with a
      sensitivity of 58%, specificity of 86% and 86% correctly classified. The results
      indicate that for the discrimination of AD from ND control subjects, measurement
      of a set of markers including Abeta1-42, ApoA1 and HPX improved diagnostic
      performance over that obtained by measurement of Abeta1-42 alone. For the
      discrimination of AD from NADD subjects, measurement of Abeta1-42 alone was
      superior.

PMID- 19863189
TI  - Urinary biomarkers suggest that estrogen-DNA adducts may play a role in the
      aetiology of non-Hodgkin lymphoma.
AB  - A variety of evidence suggests that estrogens may induce non-Hodgkin lymphoma
      (NHL). The reaction of catechol estrogen quinones with DNA to form depurinating
      estrogen-DNA adducts is hypothesized to initiate this process. These adducts are
      released from DNA, shed from cells into the bloodstream and excreted in urine.
      The aim of this study was to determine whether or not the depurinating estrogen
      DNA adducts might be involved in the aetiology of human NHL. Estrogen
      metabolites, conjugates and depurinating DNA adducts were identified and
      quantified in spot urine samples from 15 men with NHL and 30 healthy control men
      by using ultraperformance liquid chromatography/tandem mass spectrometry. The
      levels of estrogen-DNA adducts were significantly higher in the men with NHL than
      in the healthy control men. Thus, formation of estrogen-DNA adducts may play a
      critical role in the aetiology of NHL, and these adducts could be potential
      biomarkers of NHL risk.

PMID- 19863190
TI  - Reduced platelet monoamine oxidase type B activity and lymphocyte muscarinic
      receptor binding in unmedicated children with attention deficit hyperactivity
      disorder.
AB  - Several lines of evidence support the role of monoaminergic and cholinergic
      dysregulation in attention deficit hyperactivity disorder (ADHD) and the concept
      that peripheral blood neurotransmission indices may represent valuable surrogate
      CNS markers. We determined platelet MAO-B activity (p-MAO-B) and lymphocyte
      muscarinic cholinergic receptor binding (l-MR) in 44 unmedicated ADHD children
      (aged 9.1 +/- 2.87 years) and in 26 age-matched controls for comparison. Lower
      levels of p-MAO-B (approximately 35%) and l-MR (approximately 55%) in ADHD were
      observed compared with controls. Differences were gender-dependent: p-MAO-B was
      reduced in males only (5.20 +/- 2.99 vs 8.46 +/- 5.1 nmol mg(-1) protein h(-1) in
      ADHD and controls, respectively) and l-MR in females only (ADHD vs control: 6.63
      +/- 1.75 and 15.30 +/- 8.35 fmol 10(-6) cells). The clinical significance was
      corroborated by the correlation between these markers and severity of specific
      symptoms: lower p-MAO-B associated with increased inattention scores (Conners'
      teacher-rating scale); lower l-MR associated with increased score for
      oppositional-defiant disorder (ODD) (SNAP-IV); and trend towards correlation
      between increased inattention (SNAP-IV) and lower l-MR.

PMID- 19863191
TI  - Identification of exacerbations in obstructive lung disease through biomarkers.
AB  - Inflammation has been identified as an important factor for disease exacerbation
      in obstructive lung disease. In this study, we used neutrophil and eosinophil
      counts as biomarkers for exacerbation in obstructive lung disease. We conducted a
      case-control study within a cohort of patients frequenting an outpatient clinic
      of Respiratory Medicine using data from the Utrecht Patient Oriented Database
      (UPOD). Cases were patients with a hospital admission for obstructive lung
      disease in 2005. For each case, one control patient was sampled from the same
      study base. We identified 143 cases (118 patients with chronic obstructive
      pulmonary disease and 25 asthma patients) and 143 controls. Admission was
      associated with both neutrophilia (adjusted odds ratio (OR) 4.3; 95% confidence
      interval (CI) 2.2-8.5), and eosinophilia (adjusted OR 2.6; 95% CI 1.1-6.2). The
      association with eosinophilia was only seen in asthma patients. In conclusion,
      neutrophil and eosinophil counts seem to be useful biomarkers for identifying
      exacerbations in pharmacoepidemiological studies on obstructive lung disease.

PMID- 19863192
TI  - MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma.
AB  - We identified that microRNA expression changed dynamically during liver
      development and found that miR-500 is an oncofetal miRNA in liver cancer. miR-500
      was abundantly expressed in several human liver cancer cell lines and 45% of
      human hepatocellular carcinoma (HCC) tissue. Most importantly, an increased
      amount of miR-500 was found in the sera of the HCC patients. In fact, miR-500
      levels in sera of the HCC patients returned to normal after the surgical
      treatment in three HCC patients. Our findings reveal that diverse changes of
      miRNAs occur during liver development and, one of these, miR-500 is an oncofetal
      miRNA relevant to the diagnosis of human HCC.

PMID- 19863193
TI  - Radiolabeling of lipid-based nanoparticles for diagnostics and therapeutic
      applications: a comparison using different radiometals.
AB  - Radiolabeling of nanoparticles (NPs) has been performed for a variety of reasons,
      such as for studying pharmacokinetics, for imaging, or for therapy. Here, we
      describe the in vitro and in vivo evaluation of DTPA-derivatized lipid-based NP
      (DTPA-NP) radiolabeled with different radiometals, including (111)In and (99m)Tc,
      for single-photon emission computed tomography (SPECT), (68)Ga for positron
      emission tomography (PET), and (177)Lu for therapeutic applications. PEGylated
      DTPA-NP with varying DTPA amounts, different composition, and size were
      radiolabeled with (111)In, (177)Lu, and (68)Ga, using various buffers. (99m)Tc
      labeling was performed directly and by using the carbonyl aquaion,
      [(99m)Tc(H(2)O)(3)(CO)(3)](+). Stability was tested and biodistribution
      evaluated. High labeling yields (>90%) were achieved for all radionuclides and
      different liposomal formulations. Specific activities (SAs) were highest for
      (111)In (>4 MBq/mug liposome), followed by (68)Ga and (177)Lu; for (99m)Tc, high
      labeling yields and SA were only achieved by using [(99m)Tc(H(2)O)(3)(CO)(3)](+).
      Stability toward DTPA/histidine and in serum was high (>80 % RCP, 24 hours
      postpreparation).). Biodistribution in Lewis rats revealed no significant
      differences between NP in terms of DTPA loading and particle composition;
      however, different uptake patterns were found between the radionuclides used. We
      observed lower retention in blood (<3.3 %ID/g) and lower liver uptake (< 2.7
      %ID/g) for (99m)Tc- and (68)Ga, compared to (111)In-NP (blood, <4 %ID/g; liver,
      <3.6 %ID/g). Imaging potential was shown by both PET magnetic resonance imaging
      fusion imaging and SPECT imaging. Overall, our study shows that PEGylated DTPA-NP
      are suitable for radiolabeling studies with a variety of radiometals, thereby
      achieving high SA suitable for targeting applications.

PMID- 19863194
TI  - Gelatin-based delivery systems for cancer gene therapy.
AB  - Gelatin is a natural, biocompatible, nontoxic, edible, and inexpensive
      macromolecule. These properties result in its wide application in pharmaceutical,
      medical, and cosmetic products. Recently, it has been used for the delivery of
      such gene therapeutic entities as plasmid DNA. This review discusses the in vivo
      and in vitro studies using gelatin for delivery of therapeutic genes to cancerous
      cells. Recent studies show that present cancer gene therapy using gelatin is
      lacking in both efficiency and specificity in comparison with viral vectors,
      whereas complexes of therapeutic DNA with modified gelatin possibly offer a safe
      and efficient strategy for systemic administration of therapeutic genes to solid
      tumors compared to injection of naked plasmid DNA. The future of these promising
      approaches lies in the development of better techniques for preparing gelatin
      gene complexes with the aim of a gelatin-based cancer gene therapy with
      comparable efficiency to viral vectors but with the added advantage of biosafety
      for patients.

PMID- 19863195
TI  - Self-assembly and characterization of Pluronic P105 micelles for liver-targeted
      delivery of silybin.
AB  - Polymeric micelles, based on lactobionic acid (LA)-conjugated Pluronic P105
      (P105), were prepared to achieve liver-targeted delivery of silybin. In the
      triblock copolymer structure of PEO-PPO-PEO, LA was successfully conjugated with
      the terminal end of PEO to produce LA-P105. The success of synthesis was
      confirmed using FTIR and 1H NMR. The triblock copolymers with functional moiety
      were physically mixed with silybin to form micelles. Silybin-loaded LA-P105
      micelles characterized by dynamic light scattering and transmission electron
      microscopy (TEM) were uniform spherical particles. There was a remarkable
      increase in the dissolubility for silybin in LA-P105 micelle solution (627
      microg/mL) when compared with that for water (4.6 microg/mL). The pharmacokinetic
      experiments showed that the area under the curve of silybin plasma concentration
      time profile in rats for LA-P105 micelles was lower than that for P105 micelles.
      Biodistribution studies indicated that a significantly increased amount of
      silybin was accumulated in liver, suggesting that LA locating on the surface of
      the micelles played an important role in transporting an increased amount of
      silybin into liver. This polymeric vehicle is, therefore, expected to be widely
      used as target-specific delivery vehicles for diverse water-insoluble therapeutic
      and diagnostic agents.

PMID- 19863196
TI  - Monitoring safety of liposomes containing rifampicin on respiratory cell lines
      and in vitro efficacy against Mycobacterium bovis in alveolar macrophages.
AB  - Rifampicin-encapsulated liposome suspensions were prepared by a chloroform-film
      method and converted to dry powders by freeze-drying with mannitol as a
      cryoprotectant. The liposome suspension had multilamellar nanovesicles with 50%
      rifampicin encapsulation. The liposome dry powder comprised particles with a mass
      median aerodynamic diameter of 3.4 mum, with 60% present as a fine particle
      fraction. Rifampicin-encapsulated liposomes were evidently nontoxic to
      respiratory associated cells, including bronchial epithelial cells, small airway
      epithelial and alveolar macrophages (AMs). Furthermore, the liposomes did not
      activate AMs to produce interleukin-1 beta, tumor necrosis factor-alpha, and
      nitric oxide at a level that would cascade to other inflammatory effects. The
      minimum inhibitory concentrations against Mycobacterium bovis was 0.2 and 0.8
      microM for liposomes containing rifampicin and free rifampicin, respectively. The
      less negatively charged reconstituted liposome displayed the greatest activity
      against intracellular growth of M. bovis.

PMID- 19863198
TI  - HPMA-copolymer conjugates targeted to tumor endothelium using synthetic
      oligopeptides.
AB  - Synthesis and characterization of N-(2-hydroxypropyl)methacrylamide (HPMA)
      copolymer-based drug carriers targeted on specific receptors in the membrane of
      endothelial cells by oligopeptides (GRGDG, cyclo(RGDfK), and PHSCN) are described
      in this study. The copolymers containing targeting oligopeptides bound to the
      polymer via dodeca(ethylene glycol) spacer showed a receptor-specific time
      dependent uptake with selected endothelial cell lines. The polymers were labeled
      with a fluorescent dye to enable monitoring of the interaction of the polymer
      conjugate with cells using fluorescence microscopy. Cellular uptake and apoptosis
      induction have been studied in vitro using various cell lines (EA.hy926, 3T3,
      SW620, and EL4). In vivo accumulation of the conjugate specifically targeted with
      cyclo(RGDfK) within the tumor vasculature was detected using fluorescence
      intravital microscopy in mice. The conjugate targeted by cyclo(RGDfK) was
      accumulated preferentially in the periphery of the growing tumor suggesting that
      the cyclo(RGDfK) peptide targets the polymer conjugate to the site of
      neoangiogenesis, rather than to the tumor mass.

PMID- 19863197
TI  - Enhancing efficacy and mucosa-tropic distribution of an oral HIV-PsV DNA vaccine
      in animal models.
AB  - A strategy combined the oral delivery route and bovine papillomavirus (BPV)
      pseudovirus (PsV)-based human immunodeficiency virus (HIV) DNA vaccine, which has
      been proven to enhance the mucosal immunization compared with the systemic
      immunization and in general does not induce effective mucosal immune responses.
      In this study, the immune responses against the BPV expressing HIV gp41 epitopes
      (ELDKWA, NWFDIT) after oral administration in Cynomolgus monkeys (Macaca
      fascicularis) were assessed, and the biodistribution of plasmid DNA encapsulated
      in the papillomavirus-like particles (VLPs) were evaluated in murine models.
      Results showed that oral immunization with the HIV-PsV DNA vaccine in monkey
      generated p24 and gp41 epitopes-specific serum IgG. Importantly, these induced
      antibodies had been shown to neutralize HIV-1 primary strain. In addition, the
      advantage of VLPs as vehicles delivering genes had been first revealed in
      biodistribution results. Therefore, orally administered HIV-PsV DNA vaccine was
      well-tolerated, enhanced the mucosa targeting property of the plasmid DNA, and
      reduced the nontargeting distribution, which indicate that it would reduce stress
      associated with systemic vaccination.

PMID- 19863199
TI  - Predicting response to radiotherapy: evolutions and revolutions.
AB  - PURPOSE: To review the many changes which have occurred in the past decades in
      the field of predicting outcome after radiotherapy from biological
      characteristics of the tumour or normal tissue. This review will also describe
      the present state of the art and emerging trends for the future. CONCLUSIONS:
      From using explanted cells, glass electrodes, exogenous proliferation and hypoxia
      tracers, and others, there has been a move towards monitoring expression and
      mutation of genes. Initially this was possible for just one or a few genes, but
      methods are now available which allow genome-wide monitoring at either the DNA or
      RNA level. The potential advantage of this evolution is not only to predict but
      also to understand potential causes of failure, allowing more rational and
      effective interventions. Comparative genomic hybridisation, mRNA expression
      profiling, microRNA profiling and promoter methylation profiling have all shown
      promise in finding signatures correlating with outcome, including after treatment
      involving radiotherapy. Expected trends for the future are: more signatures
      relevant to radiotherapy will be discovered; signatures will be refined and
      reduced to their essentials, such that genome-wide screening will give way to
      tailored signatures, quantifiable by routine non-array technology; more focus
      will be on assays predicting which pathway-specific radiosensitising drugs will
      be effective (exploiting tumour weaknesses); more signatures will be subjected to
      validation in randomised trials; and proteomics, DNA sequencing and imaging
      methods will play progressively increasing roles.

PMID- 19863200
TI  - Multiple blood-proteins approach for early-response exposure assessment using an
      in vivo murine radiation model.
AB  - PURPOSE: The aim was to evaluate the utility of multiple blood-protein biomarkers
      for early-response assessment of radiation exposure using a murine radiation
      model system. MATERIAL AND METHODS: BALB/c male mice (8-10 weeks old) were
      exposed to whole-body 60Co gamma-rays (10 cGy min(-1)) over a broad dose range (0
      7 Gy). Blood protein biomarkers (i.e., Growth Arrest and DNA Damage Inducible
      Gene 45 or GADD45alpha, interleukin 6 or IL-6, and serum amyloid A or SAA) were
      measured by enzyme linked immunosorbent assay (ELISA) at 4, 24, 48, and 72 h
      after total-body irradiation (TBI). RESULTS: Time- and dose-dependent increases
      in the protein targets were observed. The use of multiple protein targets was
      evaluated using multiple linear regression analysis to provide dose-response
      calibration curves for dose assessment. Multivariate discriminant analysis
      demonstrated enhanced dose-dependent separation of irradiated animals from
      control as the number of biomarkers increased. CONCLUSIONS: Results from this
      study represent a proof-of-concept for multiple blood-proteins biodosimetry
      approach. It was demonstrated for the first time that protein expression profile
      could be developed not only to assess radiation exposure in male BALB/c mice but
      also to distinguish the level of radiation exposure, ranging from 1-7 Gy.

PMID- 19863201
TI  - Dose response and kinetics of foci disappearance following exposure to high- and
      low-LET ionizing radiation.
AB  - PURPOSE: The effect of different radiation qualities on (i) 53BP1 (p53 Binding
      Protein 1) and p-ATM (phosphorylated ataxia telangiectasia mutated) foci
      induction, and (ii) on the kinetics of foci disappearance was analysed. MATERIAL
      AND METHODS: Normal human skin fibroblasts were exposed to 240 kV broad-field X
      rays or targeted with individually counted helium ((3)He) particles or protons
      ((1)H) from a Charged Particle Microbeam. Anti-p-ATM and anti-53BP1 antibodies
      were used for foci visualisation via immunocytochemistry. RESULTS: 1 Gy of X-rays
      yielded approximately 33 53BP1-positive foci/cell. The ratio between the number
      of delivered particles and yielded tracks was found to be 1:1 and 3:1 after
      targeted (3)He and (1)H irradiation, respectively. It was determined that
      approximately 50% of radiation-induced damage was repaired as measured by loss of
      foci during the first 2, 6, and 10 hours following X-ray, protons, and (3)He
      irradiation, respectively. CONCLUSIONS: There was significant radiation quality
      dependence for 53BP1- and p-ATM-positive foci induction observed. Foci
      disappearance was radiation dose-independent in the samples irradiated with X
      rays. Our results confirm that kinetics of foci disappearance depends on
      radiation quality, even when individual ions are targeted to cells.

PMID- 19863202
TI  - Intermediate frequency magnetic fields generated by an induction heating (IH)
      cooktop do not affect genotoxicities and expression of heat shock proteins.
AB  - PURPOSE: The aim of this study is to evaluate the effects of intermediate
      frequency (IF) fields generated by induction heating (IH) cooktops from the
      perspective of cellular genotoxicity and stress responses. MATERIALS AND METHODS:
      We evaluated the effects of exposure to 23 kHz magnetic fields at 6.05 mT(rms)
      for 2 h on cellular genotoxicity and stress responses in vitro. The maximum
      output power in most IH cooktops is at this frequency. The magnetic flux density
      is approximately 1000 times higher than the reference level in the International
      Commission on Non-ionising Radiation Protection (ICNIRP) guidelines. For
      assessment of genotoxicity, we studied cell growth, comet assay, micronucleus
      formation and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene
      mutation. Heat shock protein (Hsp) 27, 70, 105 and phosphorylated Hsp27 were
      evaluated as indicators of the stress responses. RESULTS: We did not detect any
      effects of the IF magnetic fields on cell growth, comet assay, micronucleus
      formation, HPRT gene mutation, expression of phosphorylated Hsp27, or nuclear
      translocation of Hsp27, 70 or 105. CONCLUSIONS: Our results indicate that
      exposure to an IF magnetic field at 6.05 mT(rms) for 2 h does not cause
      detectable cellular genotoxicity, and does not induce detectable cellular stress.

PMID- 19863203
TI  - Primitive neuroectodermal tumor of the kidney in a child.
AB  - Primary renal primitive neuroectodermal tumor (PNET) is an extraordinarily rare
      neoplasm in childhood. It generally occurs in young adults and only a few
      pediatric cases have been reported. PNET in the kidney acts aggressively and the
      record shows poor therapeutic response. The authors present the case of a 16-year
      old girl who was diagnosed with renal PNET and treated with high-dosage
      chemotherapy and peripheral blood stem cell transplantation (PBSCT).

PMID- 19863204
TI  - Single-Center Experience: immunosuppressive therapy as frontline treatment for 33
      children with acquired severe aplastic anemia.
AB  - The authors retrospectively analyzed the records of 33 children with acquired
      severe aplastic anemia (SAA) diagnosed from July 1998 to October 2007 and first
      treated by immunosuppressive therapy (IST). Serial hematologic parameters,
      complications, transfusion requirements, and time to response were assessed.
      Allogeneic hematopoietic stem cell transplantation (HSCT) was attempted in 7
      patients after failure of IST (n = 6) or relapse following an initial response to
      IST (n = 1). One child died of post-transplant lymphoproliferative disorder.
      Thirty of the 33 patients are alive and well after a median follow-up of 45
      months (range, 7-116 months). Overall (transfusion-independent) response to IST
      was 73% (24/33). The actuarial 5 years survival rate was 89.4%. In this study,
      all patients with SAA received IST as standard front-line therapy. Approximately
      three-fourths of patients with SAA have durable recovery and excellent overall
      survival.

PMID- 19863205
TI  - A case of Jarcho-Levin syndrome associated with bilateral cystic renal disease
      and wilms tumor: MR imaging findings.
AB  - Jarcho-Levin syndrome (JLS) is a congenital disorder characterized by a variety
      of vertebral and costal anomalies that result in thoracic deformity. Hitherto, a
      plethora of associated anomalies have been described in several reports. In this
      report, the authors describe a case of JLS who has Wilms tumor and bilateral
      cystic renal disease. To the authors' knowledge, there is only a single case of
      JLS who presented with multiple renal cortical cysts, but none with an associated
      Wilms tumor in the literature. Additional anomalies seen in the present case that
      are related with this syndrome are also discussed.

PMID- 19863206
TI  - Testicular function after treatment for acute lymphoblastic leukemia (all) in
      prepubertal and pubertal boys.
AB  - Testicular function was evaluated in 59 male (27 prepubertal and 32 pubertal)
      survivors treated for ALL according to two different protocols. Serum inhibin B,
      FSH, testosterone, LH, and testicular volume were measured. In both groups the
      mean values of inhibin B were lower than control, whereas the other analyzed
      parameters were comparable. The inhibin B-to-FSH ratio was reduced as compared to
      the control. Testicular volume was lower than in healthy pubertal patients. The
      results show that treatment for ALL has a negative effect on spermatogenesis,
      regardless of the age at treatment and type of therapy.

PMID- 19863208
TI  - Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient
      with acute renal failure.
AB  - Strategies effective for accelerating methotrexate removal in delayed
      methotrexate excretion have not been universally accepted. The authors report a
      case of a 12-year-old girl with osteosarcoma who developed acute renal failure
      immediately after the first administration of high-dose methotrexate. Plasma
      methotrexate was effectively removed with repeated charcoal hemoperfusion in
      addition to plasma exchange and leucovorin rescue. Charcoal hemoperfusion was
      most effective for reducing plasma methotrexate with approximately 50% of
      methotrexate being reduced during each of the procedures. No rebound increase in
      MTX levels was observed. The patient received further therapy with other cancer
      drugs and has been well for 3.5 years.

PMID- 19863207
TI  - Case Study: using a continuous glucose monitoring system in a patient with
      diabetes and beta-thalassemia hemoglobinopathy.
AB  - Optimum glycemic control is extremely important in patients with diabetes
      mellitus to avoid long-term complications. Glycemic control relies mainly on the
      use of hemoglobin A1c, which unfortunately showed inaccurate results in patients
      with hemoglinopathies. The authors describe a case of beta-thalassemia with
      poorly controlled diabetes mellitus that has misleading low levels of HbA1c. The
      use of a continuous glucose monitoring system was useful in documenting her poor
      glycemic control, with prolonged periods of hyper- and hypoglycemia. Based on
      these results, her insulin regimen was adjusted and the blood glucose levels were
      greatly improved throughout and the patient was able to meet her target blood
      glucose range (72-140 mg/dL [4-7.8 mmol/L]) in 70% of the time.

PMID- 19863209
TI  - Clinical features, treatment responses, and outcome of children with idiopathic
      thrombocytopenic purpura.
AB  - The authors investigated demographics, clinical and laboratory features,
      treatment responses, and outcomes of 93 children (median age 5 years) admitted
      for idiopathic thrombocytopenic purpura (ITP). The therapy responses of high-dose
      methylprednisolone (HDMP) (n = 77) and intravenous immunoglobulin (IVIG) (n = 10)
      treatments were similar. None of the patients with hemorrhage died. Fifteen
      patients (16.1%) had progressed into chronic ITP. Seven infants had a probable
      relationship with vaccination; none of these infants progressed into chronic ITP.
      In conclusion, the overall prognosis in childhood ITP is good. The therapy
      responses of HDMP and IVIG treatments are similar. Also, ITP cases who havw
      vaccination history have a benign course.

PMID- 19863210
TI  - Splenic angiomatoid nodular transformation in a child with increased erythrocyte
      sedimentation rate.
AB  - An 11-year-old girl was referred to the authors' hospital with a complaint of
      growth retardation. Physical examination revealed splenomegaly. Laboratory
      examination revealed increased sedimentation rate. Her imaging studies showed a
      splenic mass. Splenectomy was performed and histopathological examination
      revealed sclerosing angiomatoid nodular transformation (SANT) of the spleen. The
      disease rarely affects children but it could cause growth retardation and
      increased sedimentation rate, mimicking the chronic inflammatory diseases.

PMID- 19863216
TI  - Additive endocrine therapy for advanced breast cancer - back to the future.
AB  - While novel endocrine treatment options have been implemented in the advanced -
      as well as adjuvant setting, recent results suggest a place for "old-fashioned"
      additive treatment with estrogens in advanced breast cancer. This paper reviews
      the biological rationale for endocrine therapy in general and additive treatment
      with estrogens in particular. The finding that patients becoming resistant to
      treatment with aromatase inhibitors may subsequently respond to estrogen therapy
      adds important information to our understanding of therapy resistance in general.
      Moreover, the return of a therapeutic option abandoned more than 20 years ago,
      now to be used in a different sequential setting, suggests a critical examination
      whether there may be other conventional treatment options still earning a place
      as treatment in advanced disease as well. While ablative therapies including
      surgical oophorectomy, hypophysectomy and adrenalectomy are not candidate
      treatment options due to morbidity, there are additive treatment options apart
      from estrogen therapy that may be considered. Androgens administered at
      therapeutic doses are not feasible for toxicity reasons; yet, the potential of
      adding androgens in small doses as adjuvant to aromatase inhibitors should be
      further explored. Whether patients become resistant to other treatment options
      may still benefit from megestrol acetate, remains to be explored.

PMID- 19863217
TI  - Physical activity for the affected limb and arm lymphedema after breast cancer
      surgery. A prospective, randomized controlled trial with two years follow-up.
AB  - BACKGROUND. The influence of physical activity on the development of arm
      lymphedema (ALE) after breast cancer surgery with axillary node dissection has
      been debated. We evaluated the development of ALE in two different rehabilitation
      programs: a no activity restrictions (NAR) in daily living combined with a
      moderate resistance exercise program and an activity restrictions (AR) program
      combined with a usual care program. The risk factors associated with the
      development of ALE 2 years after surgery were also evaluated. MATERIAL AND
      METHODS. Women (n = 204) with a mean age of 55+/-10 years who had axillary node
      dissection were randomized into two different rehabilitation programs that lasted
      for 6 months: NAR (n = 104) or AR (n = 100). The primary outcomes were the
      difference in arm volume between the affected and control arms (Voldiff, in ml)
      and the development of ALE. Baseline (before surgery) and follow-up tests were
      performed 3 months, 6 months, and 2 years after surgery. Data were analyzed using
      ANCOVA and regression analysis. RESULTS. Voldiff did not differ significantly
      between the two treatment groups. Arm volume increased significantly over time in
      both the affected and the control arms. The development of ALE from baseline to 2
      years increased significantly in both groups (p < 0.001). The only risk factor
      for ALE was BMI > 25 kg/m(2). CONCLUSION. Patients that undergo breast cancer
      surgery with axillary lymph node dissection should be encouraged to maintain
      physical activity in their daily lives without restrictions and without fear of
      developing ALE.

PMID- 19863218
TI  - Changes in arm morbidities and health-related quality of life after breast cancer
      surgery - a five-year follow-up study.
AB  - BACKGROUND AND PURPOSE. Many breast cancer survivors (BCS) suffer from long-term
      upper limb morbidities after axillary node dissection. The purpose of this five
      year follow-up study was to describe changes in long-term upper limb morbidities,
      physical activity level, and Health-Related Quality of Life (HRQoL) and to find
      factors that predict HRQoL five years after surgery. PATIENTS AND METHODS. This
      study included 204 women aged 55+/-10 years who had primary breast cancer surgery
      with axillary node dissection. The subjects were examined for arm volumes and arm
      lymphedema, arm pain, sensation of heaviness, shoulder function, physical
      activity level, and HRQoL, prior to surgery, and six months and five years after
      surgery. The statistical analyses used included ANOVA for repeated measures and
      multivariate linear regression. RESULTS. ALE (13%), pain (36%), and sensation of
      heaviness (21%) in the upper limbs were present five years after surgery. ALE was
      the only morbidity that continued to increase over time. Several dimensions of
      HRQoL temporarily declined after surgery, but significantly improved in the
      period from six months to five years after surgery. The significant predictive
      factors of HRQoL five years after surgery included HRQoL prior to surgery,
      physical activity level at leisure time (both prior to and at six months after
      surgery), and duration of sick leave after surgery (in weeks). CONCLUSIONS. The
      overall HRQoL improved significantly from baseline to five years, despite the
      chronic arm pain and increase in ALE. Three independent predictive factors of
      HRQoL were identified.

PMID- 19863219
TI  - An exploratory study of associations between illness perceptions and adjustment
      and changes after psychosocial rehabilitation in survivors of breast cancer.
AB  - BACKGROUND. Although psychosocial interventions have been found to be beneficial
      for cancer patients, the role of the patients' perceptions of illness in these
      interventions remains unclear. We examined illness perceptions and psychological
      adjustment (distress and QoL) among women who had survived breast cancer and
      attended a psychosocial rehabilitation course. MATERIAL AND METHODS. From an
      ongoing longitudinal study, we used data from two sub-studies with a total of 177
      survivors (145 from the descriptive study and 32 from the randomised trial). The
      survivors from the descriptive study and the half of the randomised survivors
      attended a 1-week rehabilitation course, whereas the other half of the randomised
      survivors only received standard care (no intervention). All survivors filled out
      a questionnaire 2.5 weeks before and one and six months after the course. RESULTS
      AND DISCUSSION. No differences in the change of illness perceptions and the level
      of psychological adjustment were observed between the three groups of survivors
      between baseline and one and six months of follow-up. Baseline analyses showed
      that illness perceptions were associated with distress and QoL. This study
      indicates that illness perceptions are associated with adjustment; however,
      illness perceptions did not change after participation in a one-week multi
      component rehabilitation course.

PMID- 19863220
TI  - Prevalence of depression and its related factors among Chinese women with breast
      cancer.
AB  - BACKGROUND. Little information is available regarding depression among Asian
      breast cancer survivors. METHODS. We estimated the prevalence of depression and
      its correlates among 1400 participants of a population-based cohort study of
      women with stage 0-IV breast cancer in Shanghai, China. Through in-person
      interviews conducted at 6 months and 18 months post-diagnosis and review of
      medical charts, information on sociodemographic and clinical factors and quality
      of life (QOL) was collected. Depression was measured by the 20-item Center for
      Epidemiologic Studies Depression Scale at 18 months post-diagnosis. RESULTS.
      Approximately 26% of participants had mild to severe depression and 13% fulfilled
      the criteria of clinical depression at 18 months post-diagnosis. Women with lower
      income were more likely to have depression than women with higher income
      (prevalence: 16.6% vs. 6.9% for mild depression and 17.1% vs. 5.5% for clinical
      depression, respectively). Depression was more common among women who were
      widowed (18.9%) or divorced/separated/single (16.4%) than among women who were
      married (11.8%). Women with comorbidity were more likely to have clinical
      depression (17.3% vs 11.2%). Multivariate analysis showed that low income,
      marital status, comorbidity, and low QOL scores were independent predictors for
      depression. We did not find that prevalence of depression differed by menopausal
      status, estrogen or progesterone receptor status, disease stage, or cancer
      related treatments. CONCLUSION. Depression is common among Asian women with
      breast cancer. Routine screening and prevention of depression are warranted among
      women with breast cancer.

PMID- 19863221
TI  - The expression of p53, bcl-2, bax, fas and fasL in the primary tumour and lymph
      node metastases of breast cancer.
AB  - PURPOSE. It is unknown to what extent lymph node metastases differ from primary
      tumours of breast cancer. Our aim was to investigate the similarity between
      primary breast tumours and the matching lymph node metastases in 59 breast cancer
      patients. EXPERIMENTAL DESIGN. Immunohistochemical stainings of p53, bax, bc-l2,
      fas and fasL were performed in primary tumours and the parallel lymph node
      metastases. RESULTS. When using a cut point of 10%, the concordance between
      primary tumours and parallel lymph node metastases in the expression of p53 was
      85%, bcl-2 79%, bax 69%, fas 59% and fasL 43%. In most tumours the staining
      status of p53, bcl-2 and bax in the primary tumour and the corresponding lymph
      node did not change more than 20%. However, these variables could fluctuate in
      both directions. In 15-25% of the cases, nodal expression was more than 20% lower
      than in the primary tumours, while in 10-17% of the cases, nodal expression was
      more than 20% higher than in the primary tumours. In half of the tumours, fas
      status did not change. Most fasL positive tumours lost positivity in the lymph
      node metastases or showed positively staining cancer cells only in the peripheral
      region of the node. A phenotype analysis of combined information of tumour
      fas/tumour fasL/nodal fas/nodal fasL expression (+/ - ) was assessed. The most
      frequently observed phenotype was tumour fas - /tumour fasL + /nodal fas - /nodal
      fasL- (22% of the tumours), although almost all combinations were seen.
      CONCLUSIONS. The expression of p53, bax, bcl - 2, fas and fasL is not maintained
      in the matching lymph node metastases of breast cancer. Large studies comparing
      the expression of relevant tumour biology factors in primary tumours and parallel
      lymph node metastases and their impact on therapy outcome, especially in the
      adjuvant setting, are warranted.

PMID- 19863222
TI  - Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa
      and tumour matrix metalloproteinases and plasminogen components.
AB  - BACKGROUND. Preoperative radiotherapy reduces recurrence but increases
      postoperative morbidity. The aim of this study was to explore the effect of
      radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by
      studying enzymes and growth factors involved in ECM remodeling. MATERIALS AND
      METHODS. Twenty patients with short-term preoperative radiotherapy and 12 control
      patients without radiotherapy were studied. Biopsies from rectal mucosa and
      tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9,
      TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies
      from irradiated and non-irradiated peritoneal areas were also analysed. RESULTS.
      Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal
      mucosa and tumours while calprotectin and uPA showed an increase only in the
      mucosa after irradiation. The increase of calprotectin was due to an influx of
      inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the
      tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1
      and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1
      fraction showed no statistical difference. CONCLUSIONS. This study indicates a
      radiation-induced effect on selected ECM remodeling proteases. This reaction may
      be responsible for early and late morbidity. Interference of this response might
      reduce these consequences.

PMID- 19863223
TI  - The number of identified lymph node metastases increases continuously with
      increased total lymph node recovery in pT3 colon cancer.
AB  - BACKGROUND. The positive correlation between the number of recovered benign lymph
      nodes and patient prognosis is well established for stage II colon cancer
      patients. One theory explaining this correlation focuses on potential
      understaging of cancer specimen, implying that a specimen with few examined lymph
      nodes is likely to be assigned a lower N-stage than the correct one. Understaging
      may be the result of an insufficient examination of the specimen post
      operatively, whereby few lymph nodes are recovered and potential lymph node
      metastases are overlooked. This study aims to investigate the association between
      the total lymph node harvest and the number of lymph node metastases in colon
      cancer specimen. MATERIAL AND METHODS. We studied the original pathology reports
      of 649 patients diagnosed with T3 adenocarcinoma of the colon at the Department
      of Clinical Pathology and Genetics at Linkoping University Hospital, Linkoping,
      Sweden between the years 2000 and 2008. Patient demographics, specimen staging
      data, and lymph node recovery data were collected for each case. RESULTS. We
      found a positive association between the total lymph node harvest and the number
      of lymph node metastases per specimen. For every additional recovered lymph node
      0.17 (95% CI: 0.15-0.19) metastases were detected (p < 0.001). DISCUSSION. Our
      results support the conclusion that there is no minimum number of recovered lymph
      nodes at which an accurate determination of nodal status can be assured. Rather
      than focusing on a recommended minimum number of nodes, efforts should be shifted
      towards developing methods assuring that colon cancer specimen are dissected in a
      standardized way that optimizes the lymph node harvest.

PMID- 19863224
TI  - Changes in cytokine and biomarker blood levels in patients with colorectal cancer
      during dendritic cell-based vaccination.
AB  - INTRODUCTION. Immunotherapy based on dendritic cell vaccination has exciting
      perspectives for treatment of cancer. In order to clarify immunological
      mechanisms during vaccination it is essential with intensive monitoring of the
      responses. This may lead to optimization of treatment and prediction of
      responding patients. The aim of this study was to evaluate cytokine and biomarker
      responses in patients with colorectal cancer treated with a cancer vaccine based
      on dendritic cells pulsed with an allogeneic melanoma cell lysate. MATERIAL AND
      METHODS. Plasma and serum samples were collected prior to vaccination and
      continuously during treatment. GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL
      8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a
      multiplex assay with a Luminex 100 instrument. CEA and TIMP-1 were analysed on
      ELISA platforms. RESULTS. Patients achieving stable disease showed increasing
      levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with
      progressive disease showed significant increase in CEA and TIMP-1 levels, while
      patients with stable disease showed relatively unaltered levels. CONCLUSION. The
      increased levels of key pro-inflammatory cytokines in serum of patients who
      achieved stable disease following vaccination suggest the occurrence of vaccine
      induced Th1 responses. Since Th1 responses seem to be essential in cancer
      immunotherapy this may indicate a therapeutic potential of the vaccine.

PMID- 19863225
TI  - Synchronous and metachronous skeletal osteosarcomas: the Norwegian Radium
      Hospital experience.
AB  - Background. The purpose of this work was to study clinical and histopathological
      tumor characteristics of patients treated for synchronous or metachronous
      skeletal osteosarcoma at The Norwegian Radium Hospital from January 1, 1980 to
      January 1, 2008. Patients and methods. The hospital sarcoma database and patient
      records were reviewed to identify cases with synchronous or metachronous skeletal
      osteosarcoma. Patients with more than one skeletal lesion in the absence of
      pulmonary or other soft tissue tumor manifestations were included in the study,
      and histopathological slides from these tumors were reviewed. Results. Among a
      total of 297 registered osteosarcoma patients, six with synchronous (2.0%) and 10
      with metachronous (3.4%) skeletal osteosarcomas were identified. All tumors were
      of high-grade malignancy. Treatment at the time of the first osteosarcoma
      diagnosis was in most cases wide resections and multi-agent chemotherapy
      according to international protocols, whereas the treatment for metachronous
      tumors was individualized and in general much less intensive. One patient was
      diagnosed with Li-Fraumeni syndrome, two other individuals may be suspected to
      have the same syndrome, and yet another patient had previously been treated for a
      bilateral retinoblastoma. Thirteen patients are dead, 11 from metastatic
      osteosarcoma, one from myelodysplastic syndrome, and one from wound infection and
      methotrexate-related nephrotoxicity; whereas three patients are still alive with
      no evidence of osteosarcoma. Conclusions. The prognosis for patients with
      synchronous and metachronous skeletal osteosarcoma is poor. However, because long
      term survival is seen, aggressive treatment to selected cases, e.g., patients
      with an osteosarcoma predisposing syndrome and/or late occurring metachronous
      tumours, is justified. Revealing a possible clonal relationship between these
      tumors, e.g., by karyotyping, may be of interest for estimating prognosis and
      guide therapy intensiveness.

PMID- 19863226
TI  - The role of cbl family of ubiquitin ligases in gastric cancer exosome-induced
      apoptosis of Jurkat T cells.
AB  - BACKGROUND. Exosomes are nanometer-sized vesicles with immunomodulatory
      functions, which are released by a diverse range of living cells. Although recent
      studies have shown that tumor-derived exosomes can suppress the function of T
      cells, the molecular mechanisms are not well understood. In the present study, we
      investigated the role of the Casitas B lineage lymphoma (cbl) family of ubiquitin
      ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells. MATERIALS
      AND METHODS. By serial centrifugation and sucrose gradient ultracentrifugation,
      we isolated and purified the exosomes from gastric cancer SGC7901 cells, and
      identified them by electron microscopy and Western blotting. Cell apoptosis was
      detected using propidium iodide staining. Western blotting and RT-PCR was
      exploited to evaluate the expression of proteins and mRNA, respectively. RESULTS.
      Gastric cancer exosomes induced Jurkat T cell apoptosis in a time- and dose
      dependent manner and activated caspases 3, 8 and 9. The expression of Cbl-b and c
      Cbl was up-regulated during exosome-induced apoptosis of cells. Meanwhile,
      exosomes induced ubiquitination of the p85 subunit of phosphoinositide 3-kinase
      (PI3K) and reduced downstream Akt activity. Inhibition of proteasome led to
      partial restoration of Akt activity and cell apoptosis. DISCUSSION AND
      CONCLUSIONS. The Cbl family of ubiquitin ligases might be involved in regulation
      of exosome-induced apoptosis of Jurkat T cells by increasing PI3K proteasome
      degradation, inactivation of PI3K/Akt signaling, thus mediating some effects of
      caspase activation.

PMID- 19863227
TI  - Dose prescription and optimisation based on tumour hypoxia.
AB  - INTRODUCTION. Tumour hypoxia is an important factor that confers radioresistance
      to the affected cells and could thus decrease the tumour response to
      radiotherapy. The development of advanced imaging methods that quantify both the
      extent and the spatial distribution of the hypoxic regions has created the
      premises to devise therapies that target the hypoxic regions in the tumour.
      MATERIALS AND METHODS. The present study proposes an original method to prescribe
      objectively dose distributions that focus the radiation dose to the
      radioresistant tumour regions and could therefore spare adjacent normal tissues.
      The effectiveness of the method was tested for clinically relevant simulations of
      tumour hypoxia that take into consideration dynamics and heterogeneity of
      oxygenation. RESULTS AND DISCUSSION. The results have shown that highly
      heterogeneous dose distributions may lead to significant improvements of the
      outcome only for static oxygenations. In contrast, the proposed method that
      involves the segmentation of the dose distributions and the optimisation of the
      dose prescribed to each segment to account for local heterogeneity may lead to
      significantly improved local control for clinically-relevant patterns of
      oxygenation. The clinical applicability of the method is warranted by its
      relatively easy adaptation to functional imaging of tumour hypoxia obtained with
      markers with known uptake properties.

PMID- 19863228
TI  - Quality assurance of volumetric modulated arc therapy using Elekta Synergy.
AB  - PURPOSE. Recently, Elekta has supplied volumetric modulated arc therapy (VMAT) in
      which multi-leaf collimator (MLC) shape, jaw position, collimator angle, and
      gantry speed vary continuously during gantry rotation. A quality assurance
      procedure for VMAT delivery is described. METHODS AND MATERIALS. A single-arc
      VMAT plan with 73 control points (CPs) and 5-degree gantry angle spacing for a
      prostate cancer patient has been created by ERGO + + treatment planning system
      (TPS), where MLC shapes are given by anatomic relationship between a target and
      organs at risk and the monitor unit for each CP is optimized based on given dose
      prescriptions. Actual leaf and jaw positions, gantry angles and dose rates during
      prostate VMAT delivery were recorded in every 0.25 seconds, and the errors
      between planned and actual values were evaluated. The dose re-calculation using
      these recorded data has been performed and compared with the original TPS plan
      using the gamma index. RESULTS. Typical peak errors of gantry angles, leaf
      positions, and jaw positions were 3 degrees, 0.6 mm, and 1 mm, respectively. The
      dose distribution obtained by the TPS plan and the recalculated one agreed well
      under 2%-2 mm gamma index criteria. CONCLUSIONS. Quality assurance for prostate
      VMAT delivery has been performed with a satisfied result.

PMID- 19863229
TI  - Investigation of motion sickness and inertial stability on a moving couch for
      intra-fraction motion compensation.
AB  - BACKGROUND. Respiration-induced tumor motion compensation using a treatment couch
      requires moving the patient at non-trivial speeds. The purpose of this work was
      to investigate motion sickness and stability of the patient's external surface
      due to a moving couch with respiration-comparable velocities and accelerations.
      MATERIAL AND METHODS. A couch was designed to move with a peak-peak displacement
      of 5 cm and 1 cm in the S-I and A-P directions, respectively, and a period of 3.6
      s. Fifty patients completed a 16-question motion sickness assessment
      questionnaire (MSAQ) prior to, during, and after the study. Seven optical
      reflectors affixed to the abdomen of each patient were monitored by infrared
      cameras. The relationship between reflector positions under stationary and moving
      conditions was evaluated to assess the stability of the patient's external
      surface. RESULTS AND DISCUSSION. Among the 4800 responses, 95% were 1 (no
      discomfort) of 9, and there were no scores of 6 or higher. Mild discomfort
      (scores of 4-5) was similar during couch motion and before couch motion (p =
      0.39). Mild discomfort was less common after couch motion (p = 0.039) than before
      or during couch movement. There was a near 1:1 correspondence between marker-pair
      regression coefficients and phase offset values during couch-stationary and couch
      moving conditions. Our results show that patients do not suffer motion sickness
      or external surface instability on a moving couch.

PMID- 19863230
TI  - Neutropenia during adjuvant chemotherapy of breast cancer is not a predictor of
      outcome.

PMID- 19863231
TI  - First report on prostate displacements immediately before and after treatment
      relative to the position during VMAT delivery.

PMID- 19863232
TI  - Badminton, rectal cancer and 25 kg weight gain during chemotherapy.

PMID- 19863233
TI  - Second opinions: agendas and ego.

PMID- 19863234
TI  - Hoarseness during treatment with bevacizumab and other vascular endothelial
      growth factor signalling inhibitors.

PMID- 19863235
TI  - Uncommon long-term survival in a patient with chronic myeloid leukemia.

PMID- 19863236
TI  - Choosing isolates for the evaluation of meningococcal protein vaccines.

PMID- 19863237
TI  - Importance of T-cell location rekindled: implication for tuberculosis vaccination
      strategies.

PMID- 19863238
TI  - Mandating influenza vaccination for healthcare workers.

PMID- 19863240
TI  - 10-valent pneumococcal nontypeable Haemophilus influenzae PD conjugate vaccine:
      Synflorix.
AB  - The global burden of disease due to Streptococcus pneumoniae remains high. The
      licensed 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar) has
      successfully reduced invasive disease in the USA, but serotype coverage is
      incomplete and some evidence suggests that serotype replacement has occurred.
      Recently, a new 10-valent pneumococcal nontypeable Haemophilus influenzae (NTHi)
      protein D (PD) conjugate vaccine (PHiD-CV, Synflorix) has been licensed in more
      than 40 countries, including Europe, for the prevention of invasive disease and
      acute otitis media (AOM) due to pneumococcus in infants and children. PHiD-CV is
      immunogenic in infants when administered as a three-dose primary vaccination in a
      range of schedules and has a safety profile comparable to that of 7vCRM.
      Additional serotypes in PHiD-CV (1, 5 and 7F) increase overall serotype coverage
      and improve coverage in specific age groups and against specific disease
      syndromes. The use of the PD carrier, which provided protection against AOM
      caused by NTHi in a large efficacy trial testing a prototype of the final vaccine
      formulation, suggests that PHiD-CV will also provide some protection against AOM
      due to NTHi.

PMID- 19863241
TI  - Ixiaro: a new vaccine against Japanese encephalitis.
AB  - The mosquito-borne Japanese encephalitis virus (JEV) is a major threat to human
      health in Asia. An estimated 50,000 cases occur in the region, accounting for at
      least 10,000 deaths and 15,000 cases of neuropsychiatric sequelae. A new
      purified, inactivated JEV vaccine (IC51, Ixiaro) has been developed. Since early
      2009, the vaccine has been licensed in Australia, the USA and Europe. A series of
      successful Phase III studies has been published. Results indicate a very good
      safety and efficacy profile. The vaccine promises to become a modern approach to
      active immunization against Japanese encephalitis. With the availability of a new
      product, wider use of Japanese encephalitis vaccine will be prudent in the
      future, and guidelines and recommendations should be revised.

PMID- 19863242
TI  - HSPPC-96 vaccine in metastatic melanoma patients: from the state of the art to a
      possible future.
AB  - Heat-shock proteins are highly conserved, stress-induced proteins with chaperone
      function for trafficking and delivering peptides within the different
      compartments of the cell. Tumor-derived heat-shock protein-peptide complexes
      (HSPPCs) can be used for vaccination against malignancies. In particular, the
      HSPPC-96-based vaccine vitespen (formerly Oncophage) is the first autologous
      cancer vaccine made from individual patients' tumors that has shown encouraging
      results in clinical trials. In Phase I and II clinical trials, this vaccine has
      shown activity on different malignancies, such as gastric cancer, colorectal
      cancer, pancreatic cancer, non-Hodgkin's lymphoma and chronic myelogenous
      leukemia. In Phase III clinical trials in melanoma and kidney cancer, it
      demonstrated an excellent safety profile with almost no toxicity. Heat-shock
      protein-based vaccines can be considered as a novel therapeutic approach with a
      promising role in cancer management.

PMID- 19863243
TI  - Lancet Conferences: Influenza in the Asia-Pacific.
AB  - Pandemic influenza A (H1N1) has raised global concern and as of 4 August 2009,
      more than 170,000 cases with 1428 deaths have been reported globally to the WHO.
      In response, many ongoing studies and projects are attempting to describe this
      pandemic in more detail with respect to virology, epidemiology and clinical
      management. The Lancet organized an international conference in Beijing, China on
      22-23 August 2009, immediately after the International Scientific Symposium on
      Influenza A (H1N1) Pandemic Response and Preparedness, which was organized by the
      Ministry of Health, China. The aim of the Lancet conference was to update
      scientific knowledge about both seasonal and pandemic influenza. This conference
      also attempted to provide an insight into fundamental public health and operation
      strategies to mitigate the impact of seasonal and pandemic influenza within the
      Asia-Pacific region. In this article, the authors have tried to summarize this
      conference and discuss future prospects of pandemic preparedness and response.

PMID- 19863244
TI  - Towards improved understanding of protective mechanisms induced by the BCG
      vaccine.
AB  - EVALUATION OF: Ryan AA, Nambiar JK, Wozniak TM et al. Antigen load governs the
      differential priming of CD8 T cells in response to the bacille Calmette-Guerin
      vaccine or Mycobacterium tuberculosis infection. J. Immunol. 182(11), 7172-7177
      (2009). Mycobacterium tuberculosis is the causative agent of human TB, which is
      responsible for 26% of all preventable deaths in the developing world.
      Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used as a vaccine
      against TB since 1921, with protection varying from 0 to 80%. Although the
      reasons for this variability are unclear, protection is thought to be mediated by
      Th1-type responses. CD8(+) T cells have been shown to play a role in the response
      to mycobacteria. However, the nature of the CD8(+) response induced by BCG
      requires further characterization. In the paper being evaluated, it was shown
      that the antigenic load is important for the induction of CD8(+) T-cell responses
      and subsequent protective responses. Identification of the factors affecting
      induction of CD8(+) responses against mycobacteria will facilitate studies to
      characterize their nature and provide a platform for the development of systems
      seeking to improve on protection conferred by BCG.

PMID- 19863245
TI  - Rapamycin: could it enhance vaccine efficacy?
AB  - EVALUATION OF: Araki K, Turner AP, Shaffer VO et al. mTOR regulates memory CD8 T
      cell differentiation. Nature 460(7251), 108-112 (2009). The prime goal of
      vaccination is to induce an effective memory T-cell response, because memory T
      cells have a pivotal role in adaptive immunity. When a specific pathogen is
      encountered after vaccination, memory immune cells induce an adaptive immune
      response against that pathogen, which is faster and stronger than a primary
      immune response. Therefore, the development of a successful vaccine requires a T
      cell response of adequate magnitude. Although many vaccines effectively induce
      protective immune responses against specific pathogens, some vaccines require
      boosting due to inadequate generation of memory immune cells. It was reported
      recently that rapamycin, which is used as an immunosuppressive drug for organ
      transplantation, stimulates the production of memory CD8 T cells. This means that
      rapamycin or related drugs could be used to enhance the efficacy of many types of
      vaccines.

PMID- 19863246
TI  - Update on vaccination guidelines for allergic children.
AB  - Children with allergic or atopic diseases require immunization just like non
      atopic children. However, vaccination of such children requires some special
      considerations and precautions. Children may be allergic to specific vaccine
      constituents such as gelatin or egg. Children who have suffered an apparent
      allergic reaction to a vaccine should be evaluated by an allergist to determine
      the culprit allergen and to make recommendations regarding future vaccination. In
      rare circumstances, certain vaccines may cause acute exacerbations of allergic
      diseases, but the contention that vaccination causes allergic disease is not
      substantiated by any available evidence.

PMID- 19863247
TI  - Antituberculous vaccine development: a perspective for the endemic world.
AB  - Several new antituberculous vaccine candidates that are effective against primary
      infection in preclinical animal models have now entered the early phases of
      clinical trials. Many of these clinical trials involve subunit vaccines,
      recombinant bacillus Calmette-Guerin (BCG), or improvement of BCG immunity by
      boosting with subunit vaccines or recombinant viral vectors expressing
      immunodominant TB antigens. The burning question at this stage is: will the
      current vaccines be effective in the endemic world where the diverse and complex
      challenges of TB exist? These challenges include protection of those individuals
      who are already vaccinated with BCG, those already exposed to environmental
      mycobacteria and those infected with latent TB or HIV. This review focuses on the
      available BCG vaccine, new TB vaccines in the pipeline and what type of vaccines
      are actually needed in high-burden endemic countries.

PMID- 19863248
TI  - Intussusception and rotavirus vaccination: a review of the available evidence.
AB  - Two live oral rotavirus vaccines (RotaTeq) and Rotarix) have recently been
      recommended by the WHO for inclusion into the national immunization programs of
      countries worldwide. Owing to the association of the withdrawn Rotashield vaccine
      with intussusception, these two new rotavirus vaccines underwent large clinical
      trials of over 60,000 infants each to assess safety with regard to this medical
      condition. For these two new vaccines, clinical trials and available
      postmarketing safety monitoring data do not indicate a risk of intussusception
      after vaccination, although a low-level risk cannot be excluded at present. We
      review these safety data for the new vaccines and for Rotashield to provide
      background information relevant for considering age recommendations for rotavirus
      vaccination.

PMID- 19863250
TI  - Francisella virulence: significant advances, ongoing challenges and unmet needs.
AB  - Francisella tularensis, the causative agent of tularemia, is an organism of
      concern as a potential biowarfare agent. Progress towards understanding the
      molecular basis of pathogenicity has been hampered by a lack of tools with which
      to manipulate the pathogen. However, the availability of genome sequence data for
      a range of strains and the development of a range of plasmids and mutagenesis
      protocols for use in Francisella has resulted in a huge advance in understanding.
      No licensed vaccine is yet available. Various approaches towards a new vaccine
      are being evaluated, but novel adjuvants and delivery systems are needed to
      induce the complex response required for immunity. Better animal models to more
      accurately represent human responses to infection are also required.

PMID- 19863251
TI  - Role of heavy water in biological sciences with an emphasis on
      thermostabilization of vaccines.
AB  - Preservation of vaccines, viruses and other biologicals is one of the onerous
      tasks in maintaining the quality of the products from manufacture until they
      reach the end users. Live-attenuated viral vaccines, serum immunoglobulins,
      plasma fractions and clinical samples, including tissues and body fluids, are all
      materials that usually require cold-chain maintenance during storage and
      distribution. A number of stabilizers are currently used to help retain the
      quality of these materials, in particular vaccines, during transit. Deuterium
      oxide (heavy water; D(2)O) has previously been reported to have a protective
      effect on biomolecules (proteins and nucleic acids), cells and simple
      multicellular organisms against thermal shock. Of late, the potential of D(2)O
      has been demonstrated in stabilization of the oral polio and yellow fever 17D
      vaccines. This review is the outcome of a thorough search and scan of the
      literature in a quest to explore the potential use of heavy water in the
      stabilization of veterinary biologicals. The literature search revealed this
      potential of heavy water as exemplified by successful stabilization of oral polio
      and yellow fever vaccines. Through this review, the authors wish to inform animal
      health researchers and disseminate their knowledge on the use of heavy water in
      biomolecule stabilization and its potential application in the stabilization of
      veterinary vaccines and other biologicals.

PMID- 19863249
TI  - Use of hepadnavirus core proteins as vaccine platforms.
AB  - The first virus-like particle to be tested for use as a vaccine carrier was based
      on the hepatitis B virus nucleocapsid protein. This viral subunit, while not
      infectious on its own, is a 36-nm particle that is highly immunogenic during a
      natural infection. The self-assembly and high degree of immunogenicity is
      maintained when expressed as a recombinant protein and, moreover, can confer a
      high degree of immunogenicity on foreign antigens linked to the particle, either
      chemically or genetically. This review describes the current state of the
      hepadnaviral core protein as a vaccine carrier.

PMID- 19863253
TI  - Reduction of N-glycolylneuraminic acid xenoantigen on human adipose tissue
      derived stromal cells/mesenchymal stem cells leads to safer and more useful cell
      sources for various stem cell therapies.
AB  - Adipose tissue is an attractive source for somatic stem cell therapy. Currently,
      human adipose tissue-derived stromal cells/mesenchymal stem cells (hADSCs/MSCs)
      are cultured with fetal bovine serum (FBS). Recently, however, not only human
      embryonic stem cell lines cultured on mouse feeder cells but also bone marrow
      derived human MSCs cultured with FBS were reported to express N
      glycolylneuraminic acid (Neu5Gc) xenoantigen. Human serum contains high titers of
      natural preformed antibodies against Neu5Gc. We studied the presence of Neu5Gc on
      hADSCs/MSCs cultured with FBS and human immune response mediated by Neu5Gc. Our
      data indicated that hADSCs/MSCs cultured with FBS expressed Neu5Gc and that human
      natural preformed antibodies could bind to hADSCs/MSCs. However, hADSCs/MSCs
      express complement regulatory proteins such as CD46, CD55, and CD59 and are
      largely resistant to complement-mediated cytotoxicity. hADSCs/MSCs cultured with
      FBS could be injured by antibody-dependent cell-mediated cytotoxicity mechanism.
      Further, human monocyte-derived macrophages could phagocytose hADSCs/MSCs
      cultured with FBS and this phagocytic activity was increased in the presence of
      human serum. Culturing hADSCs/MSCs with heat-inactivated human serum for a week
      could markedly reduce Neu5Gc on hADSCs/MSCs and prevent immune responses mediated
      by Neu5Gc, such as binding of human natural preformed antibodies, antibody
      dependent cell-mediated cytotoxicity, and phagocytosis. Adipogenic and osteogenic
      differentiation potentials of hADSCs/MSCs cultured with heat-inactivated human
      serum were not less than that of those cultured with FBS. For stem cell therapies
      based on hADSCs/MSCs, hADSCs/MSCs that presented Neu5Gc on their cell surfaces
      after exposure to FBS should be cleaned up to be rescued from xenogeneic
      rejection.

PMID- 19863254
TI  - Genetic variants in association studies--review of strengths and weaknesses in
      study design and current knowledge of impact on cancer risk.
AB  - Sequencing of the human genome has recently been completed and mapping of the
      complete genomic variation is ongoing. During the last decade there has been a
      huge expansion of studies of genetic variants, both with respect to association
      studies of disease risk and for studies of genetic factors of prognosis and
      treatments response, i.e., pharmacogenomics. The use of genetics to predict a
      patient's risk of disease or treatment response is one step toward an improved
      personalised prevention and screening modality for the prevention of cancer and
      treatment selection. The technology and statistical methods for completing whole
      genome tagging of variants and genome wide association studies has developed
      rapidly over the last decade. After identifying the genetic loci with the
      strongest, statistical associations with disease risk, future studies will need
      to further characterise the genotype-phenotype relationship to provide a
      biological basis for prevention and treatment decisions according to genetic
      profile. This review discusses some of the general issues and problems of study
      design; we also discuss challenges in conducting valid association studies in
      rare cancers such as paediatric brain tumours, where there is support for genetic
      susceptibility but difficulties in assembling large sample sizes. The clinical
      interpretation and implementation of genetic association studies with respect to
      disease risk and treatment is not yet well defined and remains an important area
      of future research.

PMID- 19863255
TI  - The evaluation of a biphasic osteochondral implant coupled with an electrospun
      membrane in a large animal model.
AB  - Conventional clinical therapies are unable to resolve osteochondral defects
      adequately; hence, tissue engineering solutions are sought to address the
      challenge. A biphasic implant that was seeded with mesenchymal stem cells (MSCs)
      and coupled with an electrospun membrane was evaluated as an alternative. This
      dual phase construct comprised of a polycaprolactone (PCL) cartilage scaffold and
      a PCL-tricalcium phosphate osseous matrix. Autologous MSCs were seeded into the
      entire implant via fibrin and the construct was inserted into critically sized
      osteochondral defects located at the medial condyle and patellar groove of pigs.
      The defect was resurfaced with a PCL-collagen electrospun mesh, which served as a
      substitute for periosteal flap in preventing cell leakage. Controls without
      either implanted MSCs or resurfacing membrane were included. After 6 months,
      cartilaginous repair was observed with a low occurrence of fibrocartilage at the
      medial condyle. Osteochondral repair was promoted and host cartilage degeneration
      was arrested as shown by superior glycosaminoglycan maintenance. This positive
      morphological outcome was supported by a higher relative Young's modulus, which
      indicated functional cartilage restoration. Bone ingrowth and remodeling occurred
      in all groups, with a higher degree of mineralization in the experimental group.
      Tissue repair was compromised in the absence of the implanted cells or the
      resurfacing membrane. Moreover, healing was inferior at the patellar groove when
      compared with the medial condyle and this was attributed to the native
      biomechanical features.

PMID- 19863256
TI  - Repair of rat mandibular bone defects by alveolar osteoblasts in a novel plasma
      derived albumin scaffold.
AB  - Repair of bone deficiencies in the craniofacial skeleton remains a difficult
      clinical problem. The aim of this study was to evaluate a novel albumin scaffold
      seeded with human alveolar osteoblasts and implanted into experimental mandibular
      defects. An experimental solid protein scaffold was prepared with human plasmatic
      albumin crossed with a glutaraldehyde-type agent. Microstructure of scaffold and
      mechanical properties were examined using scanning electron microscopy and a
      stress-controlled rheometer. Bilateral critical mandibular defects were created
      in eight immunodeficient rats. Defects of the right side of the mandibles
      received the cell-scaffold construct in all animals. All left mandibular defects
      were left untreated as blank controls. Sections of the defects were collected at
      5, 8, and 11 weeks postsurgery and processed for histological and
      immunohistochemical observation, computed tomography examination, and computed
      tomography digital analysis. Histologically, bone formation was observed in both
      groups at 5 weeks postsurgery, and the engineered bone became more mature after 8
      and 11 weeks, which was similar to normal bone. The origin of bone-forming cells
      within the defects and the localization of implanted human osteoblasts were
      confirmed by human vimentin expression. No bone formation could be observed at
      any control defect. Bone density after 8 weeks was significantly higher than that
      of the 5-week group (p = 0.02), and significant differences were also observed
      between 8 and 11 weeks (p < 0.01). The results indicate the clinical feasibility
      of albumin scaffold loaded with human alveolar cells and that it can be used as a
      good alternative for bone regeneration.

PMID- 19863257
TI  - Sporadic Creutzfeldt-Jakob disease--a review.
AB  - The objective is to study a patient with sporadic Creutzfeldt-Jakob disease
      (CJD). The patient, a 70-year-old woman with a history spanning over 1 month,
      with acute onset, progressive abnormal behavior, and cognitive decline with
      generalized asymmetrical myoclonic jerking, startle phenomenon, and cortical
      blindness, was referred to the hospital. On observation of clinical symptoms,
      metabolic and hematological investigations, MRI (magnetic resonance imaging), and
      EEG (electroencephalogram) were done. The clinical symptoms, MRI, and diagnostic
      EEG were suggestive of sporadic CJD. Other metabolic encephalopathies were ruled
      out. With sodium valproate and clonezepam, her myoclonic jerks improved slightly.
      As CJD is an incurable disease, no definitive treatment could be given.

PMID- 19863258
TI  - miRNA and neurons.
AB  - Micro RNAs (miRNAs) are endogenous noncoding RNAs that are important for gene
      regulation. This review provides an overview of miRNA biogenesis and mechanism of
      action. The review focuses on studies relating to the spatial and temporal
      regulation of gene expression in neurons. Studies have shown that while some
      miRNA are expressed during neuronal differentiation, others are expressed only in
      mature neurons or synapses. This review includes reports that associate miRNA
      dysfunction with neurodegenerative disorders. Finally, the review raises points
      that may be helpful for researchers in exploring areas that have remained
      unanswered vis-a-vis the biogenesis and regulatory roles of miRNAs.

PMID- 19863259
TI  - Dyslexic children show short-term memory deficits in phonological storage and
      serial rehearsal: an fMRI study.
AB  - Dyslexia is primarily associated with a phonological processing deficit. However,
      the clinical manifestation also includes a reduced verbal working memory (WM)
      span. It is unclear whether this WM impairment is caused by the phonological
      deficit or a distinct WM deficit. The main aim of this study was to investigate
      neuronal activation related to phonological storage and rehearsal of serial order
      in WM in a sample of 13-year-old dyslexic children compared with age-matched
      nondyslexic children. A sequential verbal WM task with two tasks was used. In the
      Letter Probe task, the probe consisted of a single letter and the judgment was
      for the presence or absence of that letter in the prior sequence of six letters.
      In the Sequence Probe (SP) task, the probe consisted of all six letters and the
      judgment was for a match of their serial order with the temporal order in the
      prior sequence. Group analyses as well as single-subject analysis were performed
      with the statistical parametric mapping software SPM2. In the Letter Probe task,
      the dyslexic readers showed reduced activation in the left precentral gyrus (BA6)
      compared to control group. In the Sequence Probe task, the dyslexic readers
      showed reduced activation in the prefrontal cortex and the superior parietal
      cortex (BA7) compared to the control subjects. Our findings suggest that a verbal
      WM impairment in dyslexia involves an extended neural network including the
      prefrontal cortex and the superior parietal cortex. Reduced activation in the
      left BA6 in both the Letter Probe and Sequence Probe tasks may be caused by a
      deficit in phonological processing. However, reduced bilateral activation in the
      BA7 in the Sequence Probe task only could indicate a distinct working memory
      deficit in dyslexia associated with temporal order processing.

PMID- 19863260
TI  - The effects of botulinum toxin A on ephaptic transmission in idiopathic
      hemifacial spasm.
AB  - OBJECTIVE: Lateral spreading and synkinetic responses of blink reflex are a sign
      of ephaptic transmission in idiopathic hemifacial spasm (HFS). The aim of this
      study was to evaluate the effect of botulinum toxin A (Btx A) on ephaptic
      transmission in idiopathic HFS. METHODS: Thirty-three patients with idiopathic
      HFS were investigated. Btx A was injected only into the affected orbicularis
      oculi (OC) muscle. Electrophysiological studies were performed before and three
      weeks after the Btx A injection. RESULTS: After Btx A, the latencies of motor
      response and blink reflexes elicited from the OC muscle were significantly
      increased. The lateral spreading was not obtained in the OC muscle, while the
      orbicularis oris muscle response was not changed. There were no significant
      differences in the synkinetic responses of blink reflex. During needle EMG
      examination, positive sharp waves and fibrilation potentials were observed due to
      chemodenervation only in the OC muscle. CONCLUSION: Btx A affects only the
      neuromuscular junctions of the injected muscle and has no effect upon ephaptic
      transmission.

PMID- 19863261
TI  - Soleus H-reflex gain, threshold, and amplitude as function of body posture and
      load in spinal cord intact and injured subjects.
AB  - In this study, we established parameters of the soleus H-reflex excitability in
      response to changes of posture and load in 8 chronic spinal cord injured (SCI)
      and 10 spinal-intact subjects. The soleus H-reflex recruitment curve was
      established in all subjects while they were supine, seated, and standing on a
      stable treadmill. During standing, body weight support (BWS) was provided via an
      upper body harness and ranged in SCI subjects from 20%-50% and in spinal-intact
      subjects was set at 0% and 50%. Stimuli corresponding to the H-threshold (H(th)),
      maximal H-reflex amplitude (H(max)), and 50% of H(max) as well as the reflex gain
      were estimated based on a sigmoid function of the ascending limb of the soleus H
      reflex recruitment curve. The soleus H-reflex gain, H(max) amplitude, and stimuli
      corresponding to H(th), 50% of H(max), and H(max) were increased in SCI subjects
      regardless of the body position and loading. Further, the reflex gain was not
      modulated appropriately during conditions of weight bearing in SCI subjects.
      Impaired spinal reflex excitability in SCI subjects is accompanied by changes of
      the H-reflex recruitment curve parameters regardless of presence or absence of
      body loading.

PMID- 19863262
TI  - Positron emission tomography correlates of visually-scored
      electroencephalographic waveforms during non-Rapid Eye Movement sleep.
AB  - Visually-scored, non-Rapid Eye Movement (REM) sleep electroencephalographic (EEG)
      waveform activity for each 30-s sleep scored epoch-including the number of sleep
      spindles, the number of K-complexes, and the percentage of delta waves occupying
      the epoch-was correlated with H(2)(15)O positron emission tomography. Sleep
      spindle correlations included positive correlations in the thalamus and right
      hippocampus. K-complex correlations included positive correlations in the
      frontomedian prefrontal cortex and cerebellum. Delta wave correlations included
      negative correlations in the thalamus, frontomedian prefrontal cortex, dorsal
      pons, and primary visual cortex. Each pattern of correlations may suggest a
      functional significance for these waveforms that relates to a waking outcome.

PMID- 19863263
TI  - Regional cerebral blood flow in patients with alcohol-related dementia: a SPECT
      study.
AB  - The purpose of this study was to investigate regional cerebral blood flow (rCBF)
      changes using 1110 MBq of Tc-99m ECD SPECT in alcohol-related dementia (ARD)
      patients. Twenty-five patients with ARD and 22 healthy control subjects were
      included in the study. Mini-Mental Status Examination was applied to the patients
      and controls. The ARD patients showed drastically reduced rCBF in the frontal
      cortices, basal ganglia, and thalami. The results indicate that ARD is associated
      with hypoperfusion in both cortical and subcortical regions. These findings
      support previous studies suggesting the association with both cortical and
      subcortical neuropathology in ARD patients.

PMID- 19863264
TI  - Cavernous hemangioma: a rare cause for secondary parkinsonism: a case report.
AB  - A 72-year-old female was admitted to our outpatient clinic with the complaints of
      slowed movements and sudden speeding up of her walk. She was identified to have
      cavernous angioma with left basal ganglion localization. The patient did not
      demonstrate a levodopa response and refused to have surgical treatment. The cause
      underlying this clinical presentation was identified as the chronic pressure
      brought forward by the cavernous hemangioma. We present this patient as a case
      report, because cavernous angioma with basal ganglia localization is an unusual
      cause of secondary parkinsonism.

PMID- 19863265
TI  - Tracing the origin of L-2-hydroxyglutaric aciduria in a family.
AB  - We describe late diagnosis of an adult with L-2-hydroxyglutaric aciduria (MIM
      236792) on the basis of characteristic metabolite data and mutation analysis in
      the L2HGDH gene. The patient lacked MRI abnormalities which have been purported
      to be constant or typical findings in this disease. We further report the genetic
      status of his parents and his one living sibling. Our observations underline the
      clinical heterogeneity of the syndrome of L-2-hydroxyglutaric aciduria. This
      report emphasizes the diagnostic benefit of the assessment of urinary organic
      acids not only in children, but also in adult patients with unexplained
      neurological symptoms. The patient was determined to be compound heterozygous for
      two novel missense mutations in exon 4 of the gene (c.418G>C, c.446T>G),
      resulting in amino acid exchanges from alanine to proline (p.Ala140Pro) and
      leucine to arginine (p.Leu149Arg), respectively. The mother of our patient was
      heterozygous for Ala140Pro, and the father heterozygous for Leu149Arg only.
      Mutation analysis of a healthy 49-year-old third son of the non-consanguineous
      parents revealed a normal exon 4.

PMID- 19863266
TI  - Psychotic depression: a peculiar presentation for multiple sclerosis.
AB  - Multiple sclerosis (MS) is frequently associated with a number of different
      psychiatric syndromes. Solely psychiatric syndrome may be the first clinical
      presentation of multiple sclerosis. We report a patient whose first attack was
      psychotic depression. The present case emphasizes that psychiatric symptoms can
      occur at any time during the course of the disease and, moreover, may be the
      presenting feature.

PMID- 19863267
TI  - Computational-aided identification of genes regulated by the Drosophila vnd.
AB  - Neurogenesis in Drosophila melanogaster is initiated by an ordered appearance of
      neuroblasts arranged in three columns (medial, intermediate, and lateral) in the
      neuroectoderm. In each column, specific homeodomain-containing genes are
      expressed. The ventral nervous system defective (vnd) regulates the fate of the
      cells in the medial domain of the neuroectoderm. In the present study, we
      identified Vnd-regulated genes through computational screening. Through further
      screening, we selected eight genes that were downregulated in the vnd loss-of
      function mutation. These included zfh1, uzip, CG7687, SytIV, stau, ase, scrt, and
      dpn genes. Ectopic expression of vnd, using the GAL4/UAS system, caused abnormal
      expression of all eight genes. Further, eight genes were coexpressed with that of
      vnd. Reverse-transcriptase polymerase chain reaction (RT-PCR) experiments showed
      an enhanced expression of uzip, CG7687, SytIV, and ase. Although the other four
      genes did not show an enhanced expression through RT-PCR, cytochemical and
      genetic evidence showed that these genes were regulated by Vnd. Taken together,
      the results obtained from this study indicate that expression of at least four
      genes, uzip, CG7687, SytIV, and ase, are regulated by Vnd.

PMID- 19863268
TI  - Serotonin modulates olfactory processing in the antennal lobe of Drosophila.
AB  - Sensory systems must be able to extract features of environmental cues within the
      context of the different physiological states of the organism and often temper
      their activity in a state-dependent manner via the process of neuromodulation. We
      examined the effects of the neuromodulator serotonin on a well-characterized
      sensory circuit, the antennal lobe of Drosophila melanogaster, using two-photon
      microscopy and the genetically expressed calcium indicator, G-CaMP. Serotonin
      enhances sensitivity of the antennal lobe output projection neurons in an odor
      specific manner. For odorants that sparsely activate the antennal lobe, serotonin
      enhances projection neuron responses and causes an offset of the projection
      neuron tuning curve, most likely by increasing projection neuron sensitivity.
      However, for an odorant that evokes a broad activation pattern, serotonin
      enhances projection neuron responses in some, but not all, glomeruli. Further,
      serotonin enhances the responses of inhibitory local interneurons, resulting in a
      reduction of neurotransmitter release from the olfactory sensory neurons via
      GABA(B) receptor-dependent presynaptic inhibition, which may be a mechanism
      underlying the odorant-specific modulation of projection neuron responses. Our
      data suggest that the complexity of serotonin modulation in the antennal lobe
      accommodates coding stability in a glomerular pattern and flexible projection
      neuron sensitivity under different physiological conditions.

PMID- 19863269
TI  - Effects of social isolation on neuromuscular excitability and aggressive
      behaviors in Drosophila: altered responses by Hk and gsts1, two mutations
      implicated in redox regulation.
AB  - Social deprivation is known to trigger a variety of behavioral and physiological
      modifications in animal species, but the underlying genetic and cellular
      mechanisms are not fully understood. As we described previously, adult female
      flies reared in isolation show increased frequency of aggressive behaviors than
      those reared in a group. Here, we report that isolated rearing also caused
      significantly altered nerve and muscle excitability and enhanced synaptic
      transmission at larval neuromuscular junctions (NMJs). We found that mutations of
      two genes, Hyperkinetic (Hk) and glutathione S-transferase-S1 (gsts1), alter the
      response to social isolation in Drosophila. Hk and gsts1 mutations increased
      adult female aggression and larval neuromuscular hyperexcitability, even when
      reared in a group. Unlike wild type, these behavioral and electrophysiological
      phenotypes were not further enhanced in these mutants by isolated rearing.
      Products of these two genes have been implicated in reactive oxygen species (ROS)
      metabolism. We previously reported in these mutants increased signals from an ROS
      probe at larval NMJs, and this study revealed distinct effects of isolation
      rearing on these mutants, compared to the control larvae in ROS-probe signals.
      Our data further demonstrated modified nerve and muscle excitability by a
      reducing agent, dithiothreitol. Our results suggest that altered cellular ROS
      regulation can exert pleiotropic effects on nerve, synapse, and muscle functions
      and may involve different redox mechanisms in different cell types to modify
      behavioral expressions. Therefore, ROS regulation may take part in the cellular
      responses to social isolation stress, underlying an important form of neural and
      behavioral plasticity.

PMID- 19863270
TI  - Notch signaling is required for activity-dependent synaptic plasticity at the
      Drosophila neuromuscular junction.
AB  - The cell-surface-signaling protein Notch, is required for numerous developmental
      processes and typically specifies which of two adjacent cells will adopt a non
      neuronal developmental fate. It has recently been implicated in long-term memory
      formation in mammals and Drosophila. Here, we investigated whether activity
      dependent synaptic plasticity at the neuromuscular junctions (NMJs) of third
      instar Drosophila larvae depends on Notch signaling. The length and number of
      axonal branches and number of presynaptic sites (boutons) in NMJ vary with the
      level of synaptic activity, so we increased activity at the NMJ by two
      complementary methods: increasing the chronic growth temperature of third instar
      larvae from 18 to 28 degrees C and using the double-mutant ether-a-gogo,Shaker
      (eagSh), both of which increase NMJ size and bouton count. Animals homozygous for
      the functionally null, temperature-sensitive Notch alleles, N(ts1) and N(ts2),
      displayed no activity-dependent increase in NMJ complexity when reared at the
      restrictive temperature. Dominant-negative Notch transgenic expression also
      blocked activity-dependent plasticity. Ectopic expression of wild-type Notch and
      constitutively active truncated Notch transgenes also reduced activity-dependent
      plasticity, suggesting that there is a "happy medium" level of Notch activity in
      mediating NMJ outgrowth. Last, we show that endogenous Notch is primarily
      expressed in the presynaptic cell bodies where its expression level is positively
      correlated with motor neuron activity.

PMID- 19863271
TI  - Suppressor of Hairless is required for long-term memory formation in Drosophila.
AB  - Suppressor of Hairless [Su(H)] is a DNA-binding protein of the Notch-signaling
      pathway, which is important for developmental processes and has been implicated
      in behavior plasticity. It acts as a transcriptional activator in the Notch
      pathway, but also as a repressor in the absence of Notch signaling. Our previous
      work has shown that Notch signaling contributes to long-term memory formation in
      the Drosophila adult brain. In the present report, we show that Su(H) null
      heterozygous mutants perform normally for learning, early memory, and anesthesia
      resistant memory, whereas long-term memory is impaired. Interestingly, we find
      overexpressing wild- type Su(H) also causes long-term memory defect in
      Drosophila. Significantly, induction of a heat-shock inducible Su(H)(+) transgene
      before training can fully rescue the memory defect of Su(H) mutants, thereby
      demonstrating an acute role for Su(H) in behavioral plasticity. We show that
      Su(H) is widely expressed in the adult brain. Transgenic expression of wild-type
      Su(H) in the Mushroom Bodies is sufficient to rescue the memory defect of Su(H)
      mutants. Our data clearly demonstrate that transcriptional activity of Su(H) in
      Notch signaling in the mushroom bodies is critical for the formation of long-term
      memory.

PMID- 19863272
TI  - Genetic effects in Drosophila on the potency of diverse general anesthetics: a
      distinctive pattern of altered sensitivity.
AB  - Mutations that influence the sensitivity of an organism to a volatile general
      anesthetic can be divided into two classes. In one, sensitivity to all other
      volatile agents is affected to a similar degree. Although this class may contain
      mutations of interest for understanding anesthesia, it is also likely to contain
      mutations that merely alter general health. In the second class, mutations confer
      non-uniform effects on potency (NEP), i.e., larger effects for some volatile
      anesthetics than for others. Members of this class are of special interest for
      studies of arousal and its pharmacological suppression because they not only
      avoid the pitfall of effects on global health, but also imply the existence of
      drug targets that are preferentially affected by particular agents. In this work,
      we provide the first systematic investigation of the relative frequency and
      diversity of NEP mutations in Drosophila. As a first step, we isolated and
      characterized a set of P element insertion mutations that confer altered
      sensitivity of the fruit fly to the clinical anesthetic halothane. Then we tested
      the members of this collection for their effect on the sensitivity of flies to
      five other volatile agents. Not only do we find that most of the mutations show
      non-uniform effects, they also share a characteristic arrangement of altered
      potencies (halothane > >desflurane >or= enflurane approximately isoflurane
      approximately methoxyflurane > sevoflurane). From this result, although we do not
      know how direct or indirect are the effects of the mutations, we infer the
      existence of a biologically relevant target for anesthetic action that has a
      distinct preference for halothane over other agents. Intriguingly, P element
      insertions that co-map with several NEP loci have been shown to alter the fly's
      response to cocaine and ethanol, suggesting that common genetic elements are
      involved in the response to all three drugs.

PMID- 19863276
TI  - A national survey of adult asthma prevalence by urban-rural residence U.S. 2005.
AB  - OBJECTIVES: We analyzed national data to estimate asthma prevalence among U.S.
      adults by urban-rural residence and to determine the relative contributions of
      sociodemographic and health behavior characteristics on the probability of
      reporting asthma. METHODS: We linked the 2005 Behavioral Risk Factor Surveillance
      System (BRFSS) to Urban Influence Codes (UICs), categorizing respondents into
      four urban-rural groups: metropolitan, adjacent metropolitan, micropolitan, and
      remote. BRFSS collects health data from all 50 states. UICs classify respondent's
      county as urban or rural based on population size and proximity to metropolitan
      areas. We calculated asthma prevalence estimates and generated odds ratios (ORs)
      for the probability of reporting asthma. RESULTS: Overall asthma prevalence
      (7.9%; 95%CI = 7.73-8.08) was not statistically different (p = 0.28) by urban
      rural residence. After adjusting for selected characteristics, adjacent
      metropolitan (OR = 0.96; 95%CI = 0.90-1.02) and remote (OR = 0.95; 95%CI = 0.85
      1.05) residents were less likely--and micropolitan (OR = 1.04; 95%CI = 0.93-1.16)
      residents were more likely--to report asthma compared with metropolitan
      residents; but confidence intervals included null. CONCLUSIONS: Asthma prevalence
      is as high in rural as in urban areas. Certain demographic, behavioral, and
      health care characteristics unique to place of residence might affect asthma
      prevalence. Because these results substantially change our understanding of
      asthma prevalence in rural areas, further investigation is needed to determine
      geographic-related risk factors.

PMID- 19863274
TI  - Osteogenic differentiation of mesenchymal stem cells on pregenerated
      extracellular matrix scaffolds in the absence of osteogenic cell culture
      supplements.
AB  - This study utilized a full-factorial design to investigate the effect of four
      factors: presence of whole bone marrow cells, presence of in vitro-generated
      mineralized extracellular matrix (ECM), presence of dexamethasone, and variations
      in culture duration, on the proliferation and osteogenic differentiation of
      mesenchymal stem cells (MSCs) cultured on a polymer scaffold. Electrospun
      poly(epsilon-caprolactone) (PCL) fiber mesh scaffolds were seeded with rat MSCs
      and cultured in complete osteogenic medium for 12 days to generate constructs
      containing mineralized ECM. MSCs or MSCs and whole bone marrow cells were seeded
      onto decellularized ECM constructs (PCL/ECM) or plain PCL scaffolds and cultured
      statically for 4, 8, and 16 days in medium either with or without dexamethasone.
      After each culture period, the cell number was determined by DNA analysis, and
      the osteogenic differentiation state of the cells was determined by alkaline
      phosphatase activity and calcium assays. MSCs seeded onto PCL/ECM constructs and
      cultured in medium either with or without dexamethasone demonstrated similar
      amounts of calcium deposition after 16 days. A significant increase in cell
      number over time compared with all other groups was observed when whole bone
      marrow cells were cocultured with MSCs on PCL scaffolds in medium without
      dexamethasone. This study establishes that the osteogenic differentiation of MSCs
      seeded onto ECM-containing constructs is maintained even in the absence of
      dexamethasone and that the coculture of MSCs and whole bone marrow cells without
      dexamethasone and ECM enhances the proliferation of a cell population (or
      populations) present in the whole bone marrow.

PMID- 19863277
TI  - Prevalence of asthma among adult females and males in the United States: results
      from the National Health and Nutrition Examination Survey (NHANES), 2001-2004.
AB  - BACKGROUND: The prevalence of asthma has increased over the last three decades
      with females exhibiting a higher prevalence of asthma than males. The objective
      of this study was to obtain gender-specific estimates of the prevalence of
      current and ever asthma and describe the relationships between risk factors and
      asthma by gender in US men and women ages 20 to 85. METHODS: Data for this study
      came from two cycles (2001-2002 and 2003-2004) of National Health and Nutrition
      Examination Survey (NHANES) and included 9,243 eligible adults: 4,589 females and
      4,654 males. Multiple logistic regression was used to investigate gender-specific
      associations between race/ethnicity, body mass index (BMI), sociodemographic
      characteristics, and smoking habits for current asthma and ever asthma. RESULTS:
      The prevalence of current asthma was 8.8% for women and 5.8% for men, while the
      prevalence of ever having been diagnosed with asthma was higher (13.7% and 10.4%
      for women and men, respectively). Current asthma was less prevalent in Mexican
      American women (1.9%) and men (0.9%) born in Mexico as compared to Mexican
      Americans born in the U.S. (8.7% and 5.2% for women and men, respectively) or for
      any other ethnic group. Approximately 20% of extremely obese women and men had
      ever been diagnosed with asthma; among this group, 15% reported they had current
      asthma. Results from multiple logistic regression models indicate that extreme
      obesity and living in poverty were strongly associated with current and ever
      asthma for both women and men, as was former smoking and ever asthma for men.
      CONCLUSION: As compared to previous NHANES reports, our results indicate that the
      prevalence of asthma among U.S. adults continues to increase. Further, our
      findings of marked differences among subgroups of the population suggest asthma
      related disparities for impoverished persons and greater prevalence of asthma
      among obese and extremely obese US adults.

PMID- 19863278
TI  - Delivery of asthma and allergy care in Europe.
AB  - BACKGROUND: There is no comprehensive information available concerning the way in
      which care is provided for those with allergic conditions in Europe. OBJECTIVE:
      To determine who cares for those with asthma, allergic dermatitis, and rhinitis
      in Europe and to determine the involvement of primary care and other healthcare
      professionals and the use of patient education and guidelines. METHODS: A
      questionnaire survey of colleagues in 43 institutions in 33 European countries
      with results being related to published sources of information regarding
      prevalence of allergic diseases in different countries and published data
      regarding availability of doctors and expenditure on healthcare. RESULTS: A total
      of 33 of 43 institutions completed the survey (76.7%) with information being
      obtained from 26 of the 33 countries surveyed (78.7%). There are wide differences
      in the use of different healthcare professionals in different countries, with
      those for asthma, for example, being most likely to be cared for by an
      allergologist in some countries and by a primary care physician in many others.
      There was much greater awareness of guidelines for asthma and little reported
      usage of guidelines in the management of those with allergic skin diseases, and
      while self-management education was offered most to those with asthma, there was
      a wide variation in the usage of group education. CONCLUSIONS: Many of the
      differences revealed by this survey cannot be explained by the availability of
      different healthcare professionals nor by differences in healthcare expenditure,
      and such differences need further evaluation to determine their effect on
      outcomes and the economics of healthcare so that we may determine that which is
      optimal.

PMID- 19863279
TI  - Comparison of methacholine and adenosine inhalation challenge in patients with
      suspected asthma.
AB  - OBJECTIVE: Bronchial hyperresponsiveness is usually measured by bronchial
      challenge with direct (e.g. methacholine) and indirect (e.g. adenosine) agonists.
      A prospective, randomized, crossover, single-blind study was performed to compare
      both methods in the first diagnosis of asthma. PATIENTS AND METHODS: Fifty-seven
      patients, in which asthma was suspected, were selected (21 male, 36 female).
      Fifty-four underwent both challenges following the five-breath dosimeter
      protocol. PC20 was calculated according to ATS guidelines. Data of symptoms
      developed during the challenge, PC20 methacholine and adenosine, and FEV1
      improvement after bronchodilator therapy were recorded. RESULTS: Symptoms at
      consultation were consistent with asthma in 68.4% patients, asthma and rhinitis
      in 29.8% and exercise-induced asthma in 1.8%. Atopy was reported in 93%; 49.1%
      had family history of atopy and 26.3% of asthma. The most frequent symptoms
      developed during the challenge were cough (40.4% with adenosine and 20.4% with
      methacholine) and wheezing (26.3% and 7.4% respectively), statistically
      significant differences. Bronchial challenge with MCh resulted positive in 44.4%
      of the patients and positive with AMP in 50%. Every patient with negative result
      to adenosine, was also negative to methacholine. In 94.4% subjects the result of
      both challenges was concordant (kappa index = 0.889). PC20 in both challenges
      showed poor linear correlation (Pearson r = 0.43, p < 0.05). Positivity of both
      challenges was only associated with having a positive skin prick test to danders
      (p = 0.001). Percentage of improvement after bronchodilator was 34.9% (SD12.2%)
      with adenosine challenge and 33.9% (SD17.9%) with methacholine (differences non
      statistically significant). CONCLUSIONS: Concordance in the result of both
      techniques is very high. Cough and wheezing are more frequent with adenosine,
      though not severe. PC20 with both techniques shows poor linear correlation.

PMID- 19863281
TI  - Exhaled nitric oxide in pregnant healthy and asthmatic women.
AB  - BACKGROUND: Measurement of fractioned exhaled nitric oxide (FE(NO)) is useful for
      monitoring airway inflammation in asthma. Asthma is one of the most common
      diseases complicating pregnancy, and FE(NO) may be helpful for monitoring asthma
      in pregnancy. However, some physiological alterations of FE(NO) may be expected
      during healthy pregnancy due to vascular nitric oxide production. Until now no
      study assessed the level of FE(NO) in asthmatic pregnant patients. OBJECTIVE: We
      aimed to assess the possible use and reproducibility of FE(NO) measurements in
      pregnant asthmatic women. We compared FE(NO) concentrations between four groups
      of subjects: healthy nonpregnant and pregnant females and asthmatic nonpregnant
      and pregnant patients. We also investigated the relationship between FE(NO)
      values and the level of asthma control in pregnant asthmatic patients. METHODS: A
      total of 102 female subjects (35 healthy nonpregnant and 27 healthy pregnant
      females; 20 nonpregnant and 20 pregnant asthmatic women) were included in this
      cross-sectional study. Two FE(NO) measurements were performed in each subject
      using an electrochemical sensor based device (NIOX MINO, Aerocrine, Solna,
      Sweden). Data are given as median with range. RESULTS: The repeatability of
      FE(NO) measurement was similar in pregnant and nonpregnant subjects. FE(NO)
      levels did not differ significantly between healthy pregnant versus nonpregnant
      subjects (16.0 [8, 31] vs. 16.0 [9, 35] ppb). FE(NO) levels were significantly
      increased in asthmatic women compared to healthy females (nonpregnant asthmatics:
      38 [9, 54] ppb, p < 0.001 vs. healthy nonpregnant; pregnant asthmatic patients:
      28 [10, 56] ppb; p < 0.05 vs. healthy pregnant). CONCLUSIONS: FE(NO) level is not
      influenced by healthy pregnancy. In pregnant asthmatic patients FE(NO) level is
      elevated compared to healthy pregnant subjects and correlates with the level of
      asthma control. Further studies are required to assess the use of FE(NO)
      measurement to monitor asthma in this patient group.

PMID- 19863280
TI  - Association of ambient ozone exposure with airway inflammation and allergy in
      adults with asthma.
AB  - RATIONALE: Previous studies have demonstrated associations of high ozone levels
      with increased epidemiologic as well as lung function measures of asthma
      activity. OBJECTIVES: In an observational study during the summer months, we
      hypothesized that higher ambient ozone levels are associated with more frequent
      symptoms, higher airway and systemic inflammation, as well as worse lung function
      in asthmatics as compared with non-asthmatic individuals. METHODS: Thirty-eight
      asthmatics and thirteen healthy control subjects residing in metropolitan Atlanta
      were enrolled during peak ozone season. Medical histories, quality-of-life
      questionnaires, spirometry, serum immunoglobulin (IgE), peripheral eosinophil
      counts, and exhaled nitric oxide (NO) were obtained during study visits. Personal
      ozone exposures over the 2 days before presentation were estimated based on
      location and activity surveys. MAIN RESULTS: Upper airway symptoms were more
      frequent in asthmatics. Higher levels of ozone were associated with worse airflow
      obstruction, lower quality of life scores, greater eosinophilia, and higher
      exhaled NO levels in asthmatics. Finally, both asthmatics and non-asthmatics with
      allergies showed associations between air quality and airway inflammation.
      CONCLUSIONS: In adults with asthma but not controls studied during peak ozone
      season, increasing ozone exposure predicted lower lung function and increased
      biomarkers of respiratory and systemic inflammation. These associations were
      enhanced in atopic participants, both with and without asthma. Importantly, the
      study findings were noted while atmospheric ozone levels were predominantly
      within the current and revised national air quality standards.

PMID- 19863282
TI  - Does parental involvement in pediatric emergency department asthma treatment
      affect home management?
AB  - To determine whether parents who deliver albuterol treatments in a pediatric
      emergency department with a metered dose inhaler with a spacer device (MDIS)
      report better adherence to MDIS use at home compared to parents whose children
      undergo standard nebulizer therapy. Children aged 1-5 years were randomized by
      day to usual treatment with nebulized albuterol (40 children) or to treatment by
      the parent with albuterol with an MDIS (46 children). All caregivers received
      standard discharge instructions, a spacer and an MDI. Two weeks following the
      visit, a trained research assistant blinded to the child's group status,
      administered a brief telephone questionnaire to each caretaker. At follow-up,
      children in the MDIS group were 7.5 times more likely to be using the MDIS for
      their albuterol treatments (95%CI 1.6-35.6). Involving parents in treatment of
      asthma exacerbations in the emergency department using an MDIS may improve
      adherence to MDIS use at home.

PMID- 19863283
TI  - Associations of doctor-diagnosed asthma with immigration status, age at
      immigration, and length of residence in the United States in a sample of Mexican
      American School Children in Chicago.
AB  - OBJECTIVES: Among Mexican Americans in the United States, children who were born
      in the US had higher rates of asthma than their Mexico-born peers. The purpose of
      this study was to examine the associations of doctor-diagnosed asthma with
      immigration-related variables and to investigate whether these associations could
      be explained by factors that may change with migration. METHODS: We surveyed
      parents of 2,023 school children of Mexican descent and examined the associations
      of asthma with nativity, age at immigration, and length of residence in the US
      after adjusting for potential confounding variables. RESULTS: In multivariate
      analyses, US-born children had a 2.42-fold (95% confidence interval [CI]: 1.52
      3.83) increased odds of asthma compared with their Mexico-born peers. Mexico-born
      participants who moved to the US before 2 years of age were almost twice as
      likely to experience asthma compared with Mexico-born children who moved to the
      US >or=2 years of age. In addition, Mexico-born participants who lived in the US
      for 10 years or more were 2.37 times more likely to have asthma than Mexico-born
      students who lived in the US for less than 10 years. These associations were not
      explained by a wide variety of factors such as place of residence in infancy;
      exposure to animals/pets; history of infections, Tylenol use, and antibiotic use
      in infancy; breastfeeding; exposure to environmental tobacco smoke; daycare
      attendance and number of siblings; and language use. CONCLUSIONS: Our findings
      point to the effects of nativity, age at immigration, and duration of residence
      in the US on the risk of asthma in Mexican American children, suggesting that
      potentially modifiable factors that change with migration may be linked with the
      disease. The findings of this study should stimulate further research to explain
      factors that may be responsible for the observed differentials in the risk of
      asthma among Mexican Americans.

PMID- 19863285
TI  - What does a single exhaled nitric oxide measurement tell us in asthmatic
      children?
AB  - BACKGROUND: Due to the multiple factors affecting exhaled nitric oxide (NO)
      value, physicians are often puzzled by the result of a single measurement in
      asthmatic patients. OBJECTIVE: The aim of this prospective transversal study was
      to evaluate the relative contributions to exhaled NO fraction (FE(NO)) of the
      commonly considered major NO determinants, i.e., recent symptoms (upper and lower
      respiratory tract), atopy (prick skin tests and degree of allergic exposure), and
      treatment (dose of inhaled corticosteroid [ICS]) to know what information gives a
      single measure. METHODS: FE(NO) at 50 mL/s expiratory flow was measured in 199
      asthmatic children (141 boys, age: 11.2 years +/- 2.5 years). The allergic risk
      due to pollen exposure (ARPE index) was independently evaluated by the "Reseau
      National de Surveillance Aerobiologique." RESULTS: A multivariate analysis of
      FE(NO) as dependent variable showed that explanatory variables explained 23% of
      total FE(NO) variance (symptoms > atopy > ICS). In the children without recent
      symptoms (n = 118), a FE(NO) > 23 ppb predicted atopy (sensitivity 47%,
      specificity 85%, p = 0.0006). Multiple regression only showed a trend to
      significance between FE(NO) and the dose of ICS (p = 0.057, r = - 0.19).
      Incidentally, despite similar dose of ICS, children under fluticasone (mean +/-
      SD, 259 +/- 149 microg/day) had lower FE(NO) than those under budesonide (299 +/-
      195 microg/day) (median [interquartile], 21 ppb [14-42], n = 55 versus 35 ppb [19
      47], n = 104; p = 0.007), which may be due to a higher potency of fluticasone. A
      relationship between FE(NO) and ARPE index was significant in children with
      exclusive seasonal sensitisation (n = 31, r = 0.48, p = 0.008). CONCLUSION:
      Common exhaled NO determinants weakly explain a single value of FE(NO), which
      only can confidently predict atopy.

PMID- 19863284
TI  - Physical activity and asthma symptoms among New York City Head Start Children.
AB  - The coincidence of both an obesity epidemic and an asthma epidemic among children
      in the United States has suggested that childhood overweight and sedentary
      lifestyles may be risk factors for asthma development. We therefore conducted a
      study of those factors among children enrolled in Head Start Centers located in
      areas of New York City with high asthma hospitalization rates. Data were gathered
      from 547 children through an intensive home visit, and physical activity was
      measured on 463 children using the Actiwatch accelerometer. Data on allergy and
      asthma symptoms and demographic variables were obtained from parents' responses
      to a questionnaire and complete data were available from 433 children. Overall
      physical activity was highest in warmer months, among boys, among children whose
      mothers did not work or attend school, and among children of mothers born in the
      United States. Activity was also positively associated with the number of rooms
      in the home. The season in which the activity data were collected modified many
      of the associations between demographic predictor variables and activity levels.
      Nearly half the children were above the range considered healthy weight. In cross
      sectional analyses, before and after control for demographic correlates of
      physical activity, asthma symptoms were not associated with physical activity in
      this age group. Comparing the highest quartile of activity to the lowest, the
      odds ratio for asthma was 0.91 (95% CI = 0.46, 1.80). However, the novel
      associations with physical activity that we have observed may be relevant to the
      obesity epidemic and useful for planning interventions to increase physical
      activity among preschool children living in cities in the northern United States.

PMID- 19863286
TI  - Parental occupation and risk of hospitalization for asthma in children and
      adolescents.
AB  - Our aim was to analyze risk of first hospital diagnosis of asthma in children (<
      10 years) and adolescents (10 through 19 years) in Sweden between 1970 and 2004
      by parental occupation, controlling for potential confounders. Data from the
      Multigeneration Register, in which all children born in Sweden from 1932 onward
      are registered with their parents, were linked to nationwide Hospital Register
      data. Standardized incidence ratios (SIRs) with 95% confidence intervals were
      calculated. A total of 47,019 first hospital diagnoses of asthma were recorded in
      children and 9,032 in adolescents. After accounting for age at diagnosis, sex,
      socioeconomic status, geographic region, parental history of a first hospital
      diagnosis of asthma, and period of diagnosis, 17 parental occupational groups
      were associated with increased risk of first hospital diagnosis of asthma in
      children and 9 with increased risk in adolescents. Seven parental occupational
      groups were associated with significantly increased risks in both children and
      adolescents: "nurses," "assistant nurses," "drivers," "chemical process workers,"
      "cooks and stewards," "home helpers," and "building caretakers and cleaners."
      Significantly decreased SIRs were observed for those whose parents had higher
      socioeconomic status. We conclude that parental occupation affects risk of first
      hospital diagnoses of asthma in children and adolescents.

PMID- 19863287
TI  - Markers of systemic and lung inflammation in childhood asthma.
AB  - AIM: To compare different biomarkers of inflammation in children with controlled
      and uncontrolled asthma and to investigate their relationship with other clinical
      indices of asthma control (symptoms, lung function, serum IgE, and prn beta
      agonist use). MATERIALS AND METHODS: A total of 62 consecutive asthmatic children
      (age 11 +/- 3.3 years, 32 girls) with controlled ([C], n = 19) and uncontrolled
      asthma ([NC], n = 43) were studied. Measured lung function and inflammatory
      biomarkers included: spirometry, exhaled NO (F(E)NO), high-sensitivity C-reactive
      protein (hs-CRP), peripheral blood white blood cells (WBC) counts, and
      differentials. RESULTS: Hs-CRP was significantly higher in uncontrolled than in
      controlled asthma (hs-CRP, median [IQR], mg/L; 0.56 [0.60] vs 0.25 [0.34], p =
      0.008). Discriminant analysis (backward stepwise) depicted hs-CRP and lymphocytes
      (as Z-score for absolute count) as significant discriminative factors for asthma
      control (F = 8.319, p = 0.0007) with 82.3% diagnostic accuracy. Divided into
      quartiles hs-CRP showed the significant inverse association with F(E)NO (F =
      7.359, p = 0.003, ANOVA) with no significant difference for asthma control (F =
      1.032, p = 0.386). Post-hoc analysis revealed that F(E)NO values were
      significantly lower in the third and the fourth quartile of hs-CRP in comparison
      to the first and the second one (p < 0.05 for all). CONCLUSION: In asthmatic
      children with uncontrolled asthma serum hs-CRP was increased compared to children
      with controlled asthma. Although F(E)NO values were also increased
      (insignificantly) and inversely correlated with hs-CRP they were probably
      reflecting different etiology underlying the loss of control. The role of
      peripheral blood biomarkers in asthmatics is still poorly investigated so new
      studies are required.

PMID- 19863288
TI  - Predictors of asthma-related pediatric emergency department visits and
      hospitalizations.
AB  - OBJECTIVE: Asthma is a leading cause of emergency department visits and
      hospitalizations for children in the United States. As part of a larger study,
      the purpose of this analysis was to determine which variables were most effective
      at predicting subsequent pediatric asthma-related emergency department visits and
      hospitalizations. METHODS: A retrospective, descriptive study was conducted.
      Subjects consisted of a convenience sample of 298 children admitted to a New
      England Children's Hospital in 2006 with a primary diagnosis of asthma. Data from
      two hospital databases were collected for 12 months before and 12 months after
      the 2006 admission. Basic descriptive statistics were followed by chi-square
      tests to determine which variables were associated with emergency department
      visits and hospitalizations. Logistic regression analysis was used to determine
      which variables were significant predictors of asthma-related emergency
      department visits and hospitalizations. RESULTS: Sixty-percent of all subjects
      were male. Ninety subjects experienced a total of 145 emergency department visits
      and 54 experienced a total of 70 hospitalizations. A previous emergency
      department visit was a significant predictor of both subsequent emergency
      department visits and subsequent hospitalizations. Age was also an independent
      risk factor for subsequent hospitalizations. In this sample, the risk of a
      hospitalization increased with each year increase in age. CONCLUSION: These
      findings support the importance of early identification of children with asthma
      so that appropriate asthma management can be instituted before an emergency
      department visit occurs. Furthermore, results suggest involving school-age and
      preadolescent children in the care of their asthma so that they can be equipped
      and encouraged to self-manage their own asthma.

PMID- 19863289
TI  - Health-related quality of life in college students with and without childhood
      onset asthma.
AB  - OBJECTIVE: The current study investigated whether differences existed in health
      related quality of life between individuals who self-identified as having
      childhood-onset asthma and individuals without a chronic illness. Additionally,
      the relationship between perceived illness intrusiveness and illness uncertainty
      to health-related quality of life was explored. METHODS: College undergraduates
      at least 18 years of age who self-identified as having childhood asthma were
      randomly matched by age and gender to healthy control participants. Participants
      completed a demographic form, the Mishel Uncertainty in Illness Scale-Community
      Form, the Illness Intrusiveness Scale, and the SF-36 Health Survey, a measure of
      health-related quality of life. RESULTS: Participants with asthma had
      significantly lower scores on the total and mental health-related quality of life
      scales than did healthy control subjects. There were no significant differences
      between self-identified participants with asthma and matched healthy control
      subjects on physical health-related quality of life scales. Illness intrusiveness
      was not related to either the physical (e.g., physical functioning, general
      health) or mental health-related quality of life. Higher levels of illness
      uncertainty were significantly related to higher levels of mental health-related
      quality of life (e.g., vitality, mental health). In addition, participants with
      asthma scored significantly lower than healthy controls on the social functioning
      and role-emotional subscales. CONCLUSION: The current study adds to the extant
      literature by examining the relationships between illness intrusiveness, illness
      uncertainty, and health-related quality of life among a young adult population.
      College students with asthma appear to be at risk for diminished quality of life
      compared to a healthy comparison group. Further examination of various domains of
      health-related quality of life among older adolescents and young adults with
      childhood asthma is needed.

PMID- 19863290
TI  - Chromosome instability on children with asthma.
AB  - BACKGROUND: Asthma is a complex disease with multiple interactions between
      genetic and environmental factors. OBJECTIVE: The aim of our study was to
      investigate the possible genetic instability in asthmatic patients (AP) with
      asthma in human cultured peripheral blood lymphocytes. Furthermore, the presence
      of either cytostaticity or cytotoxicity was demonstrated. METHODS: Human
      peripheral blood lymphocytes were cultured from 18 admitted children to the
      Pediatric Clinic of the University Hospital of Alexandroupolis (average age 7.2
      years), and 9 healthy blood donors were used as control subjects (average age 6.5
      years), none of whom was receiving drugs for medical or other reasons. RESULTS: A
      significant (p < 0.05) increase in spontaneous sister chromatid exchanges (SCEs)
      frequency in asthmatic patients compared with control subjects was observed. No
      statistically significant modification in the spontaneous proliferation rate
      index (PRI) in AP compared with the controls was demonstrated. Finally, MMC
      induced a statistically significant increase in SCEs frequency both to controls
      and to AP, with the MMC-induced SCEs rates in AP being statistically (p < 0.01)
      higher compared to the MMC-induced SCEs in controls. CONCLUSION: We try to
      improve a new diagnostic process of possible genetic instability by a combination
      of genotoxic, cytostatic and cytotoxic effects of asthma on human peripheral
      lymphocytes.

PMID- 19863291
TI  - Peak expiratory flow in normals: comparison of the mini Wright versus spirometric
      predicted peak flows.
AB  - OBJECTIVES: U.S. prediction equation estimated peak flows were obtained
      spirometrically and may not correctly predict actual peak flows that are obtained
      using a peak flow meter. The purpose of this investigation was to compare actual
      Mini Wright peak flows in normal volunteers as compared with spirometric
      predicted values to determine whether they are similar. METHODS: Nonsmoking,
      nonobese adult volunteers with no history of lung disease underwent peak flow
      testing with an American Thoracic Society (ATS) Mini Wright peak flow meter. All
      subjects did three peak flows by taking a maximal deep breath and expiring as
      hard and fast as possible while in the standing position. The best of three
      efforts was taken as the peak flow value for analysis and compared with
      prediction equation estimates. The paired t test compared differences between
      actual and predicted values. The concordance correlation coefficient evaluated
      whether the actual peak flows were interchangeable with predicted. RESULTS:
      Seventy-two volunteers, average age 44 +/- 10 years and mean BMI 25.2 +/- 2.9,
      were included. The Mini Wright peak flow values of 508 +/- 113 L/min were
      significantly different than the predicted values of 471 +/- 84 (p < 0.01). The
      predicted values were reduced on average by 7.3 percent compared to actual
      values. The concordance correlation coefficient was 0.72 (95% C.I.; 0.60 - 0.80)
      suggesting the actual and predicted values are not interchangeable. CONCLUSIONS:
      The ATS Mini Wright peak flow values are slightly higher than spirometrically
      derived predicted peak flow values in subjects without lung disease. This
      suggests that predicted peak flow values should be generated by a peak flow meter
      and would be higher than current spirometrically predicted values.

PMID- 19863292
TI  - Is Bjerkandera adusta Important to fungus-associated chronic cough as an
      allergen? Eight cases' reports.
AB  - BACKGROUND: Recently, we have reported a new clinical disease concept called
      fungus-associated chronic cough (FACC), which entailed the following
      manifestations: (1) chronic cough; (2) the presence of environmental fungi,
      particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical
      response to antifungal drugs. To clarify the relationship between the exposure to
      environmental fungi and the development of cough attacks, we reviewed the
      clinical records of patients with FACC and performed a molecular biological
      analysis of the BM fungi. METHODS: We successfully selected 8 patients with
      chronic cough, wherein a sputum culture yielded B. adusta beforehand; moreover,
      we conducted allergological tests such as the immediate-type skin test, a
      serological test, bronchoprovocation test, and lymphocyte stimulation test (LST),
      using the antigenic solution of B. adusta. The efficacy of individualized therapy
      and the clinical manifestations in the eight patients were examined. RESULTS: All
      the eight patients were diagnosed with FACC. Although three patients who did not
      show a positive reaction to the bronchoprovocation test or LST showed excellent
      clinical response to anti-fungal drugs; other 5 patients who showed a positive
      reaction to the bronchoprovocation test and/or LST seemed to be more intractable
      because of taking a longer time for complete remission and more frequent
      recurrence of cough. CONCLUSION: It was suggested that so-called allergic fungal
      cough (AFC), which is characterized by sensitization to B. adusta, may be
      included in a part of chronic intractable cough.

PMID- 19863293
TI  - Primary benign bronchial schwannoma presenting as asthma.
AB  - Recurrent wheezing in children is frequently due to asthma and responds to
      bronchodilator therapy. We report a case of a 13-year old boy with a 2-year
      history of presumed asthma not responding to bronchodilator therapy. Bronchoscopy
      revealed a right main bronchus tumor, which was diagnosed as bronchial schwannoma
      after resection by sleeve lobectomy. We review the literature on this tumor.

PMID- 19863297
TI  - Temporal profile and clinical significance of serum neuron-specific enolase and
      S100 in ischemic and hemorrhagic stroke.
AB  - BACKGROUND: Neuron-specific enolase (NSE) and S100 protein are implicated in
      several brain injuries, including stroke. Our objective was to analyze the
      temporal profile and the clinical significance of NSE and S-100 in acute ischemic
      (IS) and intracerebral hemorrhage (ICH). METHODS: We studied 224 patients with IS
      and 44 patients with ICH. Computerized tomography (CT) scans were performed to
      assess infarct volume. Stroke severity was evaluated using the National Institute
      of Health Stroke Scale (NIHSS), and functional outcome at 3 months with the
      modified Rankin Scale (mRS). Serum NSE and S100 protein were measured using an
      electrochemiluminescence-immunoassay. RESULTS: Peak values were found at 72 h for
      NSE and at 24 h for S100 in IS. For ICH, peak values were found at 24 h for both
      NSE and S100. At these time intervals S100 and NSE correlated with the NIHSS
      score and were independently associated with poor outcome. CONCLUSIONS: High
      serum NSE and S100 are associated with poor outcome in IS, and high serum NSE is
      associated with poor outcome in ICH. These findings suggest the potential utility
      of NSE and S100 as prognostic markers for acute stroke.

PMID- 19863298
TI  - ROS1 Asp2213Asn polymorphism is not associated with coronary artery disease in a
      Greek case-control study.
AB  - BACKGROUND: Rs619203 (Cys2229Ser) and rs529038 (Asp2213Asn) polymorphisms in the
      ROS1 gene have been studied in relation to myocardial infarction (MI) yielding
      inconsistent results. We investigated the role of ROS1 rs529038 polymorphism in
      coronary artery disease (CAD) in Greeks using a case-control study. METHODS:
      Genotyping for rs529038 polymorphism was performed using a multiplex PCR
      technique in patients with CAD (n=294) and controls (n=311). Logistic regression
      analysis was used to calculate crude and adjusted odds ratios (ORs). RESULTS:
      Logistic regression analysis did not show any statistically significant effect of
      ROS1 polymorphism in the occurrence of CAD (AG vs. AA, OR: 1.08, p=0.635; GG vs.
      AA, OR: 0.62, p=0.220). Adjustment for confounding factors gave similar results,
      irrespective of the type of disease (i.e., stable coronary artery disease vs.
      acute coronary syndrome). CONCLUSIONS: Our findings do not support the hypothesis
      that ROS1 rs529038 polymorphism is an important contributing factor in the
      etiology of CAD in the Greek population.

PMID- 19863299
TI  - Haplotype-based association of regulator of G-protein signaling 5 gene
      polymorphisms with essential hypertension and metabolic parameters in Chinese.
AB  - BACKGROUND: A recent genome-wide linkage study mapped blood pressure (BP)-related
      loci on human chromosome 1q and identified the regulator of G-protein signaling 5
      (RGS5) as a candidate for regulation of BP. Thus, we assessed the relationship
      between RGS5 genetic polymorphisms and essential hypertension (EH) in Chinese.
      METHODS: A total of 906 patients with EH and 894 age- and gender-matched
      normotensive (NT) controls were enrolled. Sixteen single nucleotide polymorphisms
      (SNPs) in RGS5 were genotyped. RESULTS: There were no significant differences in
      the overall distributions of the genotypic and allelic frequencies for each SNPs
      between the two groups. However, in haplotype analysis, significant differences
      for the overall distributions were noted for four haplotypes constructed by five
      SNPs (rs12041294C/T, rs10917690A/G, rs10917695T/C, rs10917696T/C and
      rs2662774G/A), viz. H(2) (C-A-C-T-A) (p=0.038), H(5) (C-G-T-T-G) (p=0.001), H(6)
      (T-G-C-T-A) (p=0.021) and H(12) (T-A-T-T-G) (p=0.023). Serum concentrations of
      high- and low-density lipoprotein cholesterol showed significant associations
      with haplotypes revealed by a global test (p=0.0001 and 0.0309). CONCLUSIONS:
      Multiple SNPs in combination in RGS5 may confer risk for hypertension. Our
      results also lend support for the effect of RGS5 SNPs on lipid metabolism.
      Further studies are warranted to find the causal SNPs in RGS5 for EH.

PMID- 19863300
TI  - Appropriate utilization of clinical laboratory tests.
AB  - BACKGROUND: The use of laboratory tests has been increasing in recent years due
      to various factors affecting laboratories, physicians, legal aspects, or patients
      themselves. METHODS: The efficacy of laboratory tests must be evaluated on the
      basis of the clinical benefits that they provide in terms of prevention,
      diagnosis, follow-up, or treatment; with the aim of optimizing health results in
      general. RESULTS: There are techniques that can be used to determine the clinical
      validity of the efficacy, effectiveness, and safety of treatment or preventive
      measures performed on individuals with abnormal tests, as well as providing an
      economic evaluation of the process. Once the test is incorporated into clinical
      service, it must be evaluated by retrospective audits in test utilization. To
      improve the use of laboratory tests, many strategies have been devised that
      incorporate clinical practice guidelines (CPGs), the conduct of professionals and
      the patients, and organization of the process. We discuss the importance of the
      involvement of health professionals. CONCLUSIONS: Strategies in relation to CPGs,
      conduct of professionals, conduct of patients, or organization of health care
      processes improve the use of tests in relation to clinical processes. Laboratory
      professionals have the appropriate knowledge and can improve the quality and
      efficacy of health care.

PMID- 19863301
TI  - Quantitation of RNA decay in dried blood spots during 20 years of storage.
AB  - BACKGROUND: Diseases with an onset during childhood or adult life can have their
      origin during fetal life or at birth. Neonatal blood dried on filter paper
      (Guthrie cards) collected for screening purposes is routinely stored for decades.
      In addition to clinical use, these filters in combination with patient registers
      constitute an invaluable resource for epidemiological and pathophysiological
      research. Although RNA has been successfully recovered from such filters even
      after decades of storage, the potential decay of RNA over time has not previously
      been investigated using quantitative methods. METHODS: Filter papers (n=5) with
      dried blood spots from the Swedish National PKU register, stored for 1, 5, 10, 15
      or 20 years were randomly selected. RNA was isolated from each sample,
      quantitated by spectrophotometry and reverse transcribed following DNase I
      treatment. Amplifiable cDNA was subsequently detected by real-time PCR using
      primers specific for transcripts encoding beta-actin. RESULTS: Transcripts
      encoding beta-actin were detected in all 25 samples analyzed at a mean threshold
      cycle (Ct) of 25 (SD 1.9). A one-way ANOVA indicated no significant effect of
      storage time on Ct values. CONCLUSIONS: The lack of significant decay of RNA in
      dried blood filters stored for up to 20 years suggests that such filters are
      useful for studies of RNA determinants of diseases with an onset in childhood as
      well as adult life.

PMID- 19863302
TI  - Hearing and vestibular functions after plugging surgery for the posterior
      semicircular canal.
AB  - CONCLUSIONS: Results of audiometry, caloric testing and vestibular evoked
      myogenic potential (VEMP) testing were hardly influenced by plugging surgery.
      OBJECTIVE: To evaluate the influence of surgical plugging of the posterior
      semicircular canal on inner ear function in patients with benign paroxysmal
      positional vertigo (BPPV). SUBJECTS AND METHODS: The subjects were five
      consecutive patients with intractable BPPV who underwent plugging surgery. The
      following functions of the inner ear were examined before and 6 months after
      surgery. Cochlea function was evaluated by the average hearing level of three
      frequencies (500, 1000 and 2000 Hz), that of the semicircular canal by canal
      paresis percent (CP%) in caloric testing and that of the otolith by the left
      right difference ratio on VEMP testing. RESULTS: Positional vertigo was resolved
      in all patients. One subject was completely deaf before and after surgery. The
      average hearing level did not change more than 10 dB after surgery in the other
      four cases. CP% did not worsen more than 10% in any case. The VEMP results after
      surgery did not change more than 10% from before surgery in any case.

PMID- 19863303
TI  - An animal model of cochlear implantation with an intracochlear fluid delivery
      system.
AB  - CONCLUSION: An animal model of cochlear implantation with a local intracochlear
      fluid through a microcatheter included in the array has been developed. It is
      suitable for evaluation of putative therapeutic agents to decrease cochlear
      trauma after cochlear implantation. OBJECTIVES: The purpose of this study was to
      design an animal model of cochlear implantation with an intracochlear fluid
      delivery system to demonstrate the stability of the device and study the patterns
      of hearing loss. MATERIALS AND METHODS: Eleven guinea pigs were implanted with a
      prototype array that comprised one electrode and a microcatheter connected to an
      osmotic minipump containing saline serum. Three animals were implanted with the
      same electrode carrier without any connection to the minipump. Preoperative and
      postoperative audiometry was assessed by means of auditory brainstem response
      (ABR, clicks). Morphological analyses were performed with imaging and
      histological techniques. RESULTS: In the saline serum perfusion group an initial
      ABR threshold shift of 33+/-3.0 dB was observed and remained stable over time. In
      the unconnected group a similar threshold shift was observed at day 7. At day 30
      CT scanning showed that the implants remained in a stable position. Histological
      analysis revealed fibrosis around the implant in the basal turn but preservation
      of inner ear structures in apical turns.

PMID- 19863304
TI  - Utility of immunologic parameters in the evaluation of Meniere's disease.
AB  - CONCLUSION: Because of the lack of association between a positive test and
      response to corticosteroid treatment, at present, detection of anti-HSP 70
      antibody, tumor necrosis factor (TNF)-alpha, erythrocyte sedimentation rate
      (ESR), or antinuclear antibody (ANA), does not offer clinically useful
      information in the treatment of Meniere's disease (MD). OBJECTIVES: The study was
      designed to investigate the performance of various laboratory tests, including
      anti-HSP 70, TNF-alpha, ESR, ANA, and anti-phospholipid antibodies, in the
      diagnosis and treatment response of patients with MD. PATIENTS AND METHODS:
      Thirty patients who presented with MD and 30 healthy people were selected as
      study and control groups, respectively. The laboratory panel included the
      following tests: anti-HSP 70 antibody immunoassay, TNF-alpha, ESR, ANA, and anti
      phospholipid antibodies. The study group was given corticosteroid therapy and
      separated into two groups: the corticosteroid responders and the corticosteroid
      non-responders. In the follow-up, repeat audiograms were evaluated to determine
      the response to treatment. RESULTS: TNF-alpha was found at significantly lower
      titers in the study group when compared with the control group (p<0.05). Anti-HSP
      70 was not found in high titers in the study group. ANA positivity in patients
      with MD was not statistically different from the control group. There was no
      significant difference in the treatment response for any of the parameters
      tested.

PMID- 19863305
TI  - Assessment of the reuniting duct by three-dimensional CT rendering.
AB  - CONCLUSION: The rendering strategy sometimes induces misunderstanding of the
      image. We demonstrated a more accurate image of the bony groove of the reuniting
      duct using three-dimensional (3D) cone beam CT image, which was less affected by
      artifacts created by the rendering effect. OBJECTIVE: To obtain a suitable image
      of the groove of the reuniting duct for future morphological study. MATERIALS AND
      METHODS: The grooves of reuniting ducts in 10 healthy human subjects were
      analyzed by cone beam CT in comparison with a cadaver study. RESULTS: We could
      obtain more accurate 3D CT images of the bony groove in human subjects by
      checking the landmarks of 3D CT images.

PMID- 19863306
TI  - Endolymphatic space imaging in patients with delayed endolymphatic hydrops.
AB  - CONCLUSION: Magnetic resonance imaging (MRI) after intratympanic gadolinium
      injection can reveal endolymphatic hydrops (ELH) in patients with delayed ELH
      (DELH). Patients with contralateral DELH may have bilateral ELH. OBJECTIVE: DELH
      has previously been diagnosed based on clinical history, hearing and vestibular
      examinations. DELH is classified into three types: ipsilateral, contralateral and
      bilateral indicate the side with the longstanding hearing loss. Ipsilateral DELH
      occurs in the ear with a profound hearing loss, contralateral DELH in the better
      hearing ear and bilateral DELH in both ears. Imaging diagnosis of the
      endolymphatic space may add a new dimension to the diagnosis and treatment of
      DELH. PATIENTS AND METHODS: Gadodiamide hydrate was diluted eightfold with
      saline. The diluted gadodiamide hydrate was injected intratympanically through
      the tympanic membrane in two patients with ipsilateral DELH and five patients
      with contralateral DELH. One day after the injection, 3 Tesla MRI was performed
      to evaluate the endolymphatic space. RESULTS: ELH was observed in all patients.
      In three patients who underwent bilateral intratympanic injection of gadolinium
      and were diagnosed with contralateral DELH, ELH was observed bilaterally. In one
      of these three patients, ELH was observed in the cochlea on the left and in the
      vestibule on the right.

PMID- 19863307
TI  - Estrogen receptors in the inner ear during different stages of pregnancy and
      development in the rat.
AB  - CONCLUSION: ERalpha and ERbeta are present in the inner ear and are up- and down
      regulated depending on the stage of maturation, development and pregnancy,
      suggesting that estrogen may have an effect on the cochlea during various stages
      of life. No estrogen receptors (ERs) were found in the cochlea of the developing
      fetus, which suggests that estrogen does not have an effect on the cochlea during
      gestation. OBJECTIVE: To investigate the distribution of ERs in the cochlea
      during pregnancy, maturation and development in a female rat model. MATERIALS AND
      METHODS: The cochleas of 24 rats in 4 groups in different time periods of
      maturation (21 and 56 days old) and pregnancy (day 8 and 18 of pregnancy) and 16
      fetuses at gestational ages of 8 and 18 days were collected. All specimens were
      stained for ERs using standard immunohistochemical techniques. RESULTS: ERs are
      present in the cochlea of the rat and vary during maturation and pregnancy. No
      ERs were found in the fetal cochleas. Of the non-fetal time points measured, the
      expression levels of ERs in the rat cochlea were highest at the postnatal age of
      21 days and were lowest during late pregnancy (day 18).

PMID- 19863308
TI  - Pressure changes in the human middle ear without opening the eustachian tube.
AB  - CONCLUSION: By means of a direct, though non-invasive experiment on healthy
      humans we could demonstrate that middle ear (ME) pressure decreases when the
      eustachian tube (ET) does not open. Thus with a very simple method the basic
      theory of continuous gas loss from the ME into the circulation and the
      replenishment of the loss through the ET could be validated. OBJECTIVES: To
      record changes in ME pressure over a period of time in normal human ears, while
      the ET is kept closed. SUBJECTS AND METHODS: On-line tympanometry was carried out
      in three subjects, who refrained from swallowing for 20-120 min. RESULTS: During
      the time when the ET was kept closed by refraining from swallowing, tympanometric
      monotonous pressure decrease was recorded. Once the tested subject could not
      refrain from swallowing any longer and swallowed again, ME pressure equalized
      immediately.

PMID- 19863309
TI  - The imbalance of enzymatic antioxidants in cholesteatoma.
AB  - CONCLUSION: Depletion of enzymatic antioxidants was observed in cholesteatoma.
      However, a relationship between activity of enzymatic antioxidants and the extent
      of bone erosion was not found. OBJECTIVES: To measure the level of major
      enzymatic antioxidants in cholesteatoma, and to investigate the relationship
      between the level of enzymatic antioxidants and the extent of bone erosion.
      PATIENTS AND METHODS: The cholesteatoma and skin samples were obtained during
      otologic surgeries. All cases were grouped according to the number of bone
      erosion sites. Samples were examined biochemically and the levels of enzymatic
      antioxidants were measured. The results were analyzed statistically. RESULTS:
      Thirteen patients were included in the study. The mean level of superoxide
      dismutase in cholesteatoma and skin was 45.87 U/mg and 71.04 U/mg, respectively.
      When the catalase level was evaluated, the mean level was 5.04 U/g in
      cholesteatoma and 11.62 U/g in skin. The mean level of glutathione peroxidase in
      cholesteatoma and skin was 12.13 IU/g and 236.74 IU/g, respectively. All the
      results of cholesteatoma and skin samples were compared through non-parametric
      tests and statistically significant differences were found. However, a
      statistically significant difference between the levels of enzymatic antioxidants
      and the extent of bone erosion was not observed.

PMID- 19863310
TI  - Acute tympanic membrane perforations and the early immunological response in
      rats.
AB  - CONCLUSIONS: This study showed that macrophages, B cells, and T cells occurred at
      different frequencies, localizations, and times after acute laser tympanic
      membrane perforation. Immunological cells were most prevalent in the
      proliferative mass adjacent to the annulus region. The cellular immunological
      response in freshly perforated eardrums was unexpectedly aggressive. OBJECTIVES:
      To study the occurrence of immunocompetent cells during the healing process of
      fresh perforated tympanic membranes. The information could be used to develop
      alternative outpatient procedures in the cure of chronic perforations, replacing
      conventional surgery. MATERIALS AND METHODS: A laser myringotomy was carried out
      in Sprague-Dawley rats, which were sacrificed at 3 and 6 days after the
      myringotomy. Tympanic membrane sections were stained immunohistochemically
      according to the avidin-biotin method, targeting macrophages, B cells, and T
      cells. Semi-quantification was performed; positive cells were counted and mean
      values were calculated. RESULTS: Macrophages and B cells were most frequent at
      day 6 and T cells at day 3 after laser myringotomy. B cells were the most
      prevalent studied cell type. T cells peaked at day 3, after which they decreased
      in number. Most immunocompetent cells were observed in the proliferative mass at
      the edge of the perforation.

PMID- 19863311
TI  - Vestibular evoked myogenic potentials of children with inner ear malformations
      before and after cochlear implantation.
AB  - CONCLUSIONS: Our results show that among the patients with inner ear
      malformations, there were two patients with sensory cells of sacculus and
      inferior vestibular neurons and at least five patients with inferior vestibular
      neurons only, but no patients without sensory cells and vestibular neurons, as
      determined on the basis of vestibular evoked myogenic potentials (VEMPs).
      OBJECTIVE: The aim of this study was to investigate whether sensory cells of
      sacculus or inferior vestibular neurons or both are present in cochlear implant
      patients with inner ear malformations, particularly common cavity (CC) deformity,
      using VEMPs. PATIENTS AND METHODS: Seven children with inner ear malformation who
      underwent cochlear implantation (CI) participated in this study. The patients had
      CC deformity (n=2), incomplete partition type I (n=2), incomplete partition type
      II (n=1), or a narrow internal auditory canal (IAC) (n=2). It was possible to
      record VEMPs before and after CI in three patients and not before but after CI in
      four patients. After surgery, VEMPs were recorded with the cochlear implant
      device switched both off and on. RESULTS: Before the CI, two patients showed
      VEMPs and one patient showed no VEMPs, whereas in four patients no VEMPs could be
      recorded. All the patients showed VEMPs with the cochlear implant on.

PMID- 19863312
TI  - Vestibular evoked myogenic potentials in chronic otitis media before and after
      surgery.
AB  - CONCLUSION: The pathology of chronic otitis media (COM) could delay and reduce
      the energy transfer of sound to the inner ear. The significant improvement of
      postoperative vestibular evoked myogenic potential (VEMP) response rate and p13
      latencies in the group of patients with no or negative postoperative ABG gain
      provided evidence that the sound energy inducing a VEMP might be different from
      the energy producing the auditory perception. OBJECTIVE: To evaluate the VEMP in
      patients with COM before and after surgery. SUBJECTS AND METHODS: Twenty-four
      subjects with unilateral COM were enrolled. A pure tone audiogram and VEMP using
      500 Hz unilateral short tone-burst stimulations were recorded before and 3 months
      after surgery. The postoperative VEMP responses were compared with the responses
      before surgery and the healthy controls. RESULTS: After surgery, the 500 Hz air
      bone gap (ABG) decreased significantly and the VEMP response rate increased
      significantly from 41.7% to 66.7% (p<0.05, bi-test). However, both the
      preoperative and postoperative p13 latencies were significantly longer than those
      of the healthy controls (p<0.05, Wilcoxon rank-sum test). In the 18 patients
      whose 500 Hz ABG did not improve with surgery, the p13 latencies were
      significantly shorter postoperatively (p<0.05, sign test), and the response rate
      also improved significantly from 44.4% (8/18) to 77.8% (14/18) (p<0.05, bi-test).

PMID- 19863314
TI  - Bedside therapeutic experiences with horizontal canal benign paroxysmal
      positional vertigo (cupulolithiasis).
AB  - CONCLUSIONS: After forced prolonged position type one (FPP-one) and the
      appropriate repositioning maneuvers, or FPP-two, 95.45% of patients with
      cupulolithiasis of the horizontal semicircular canal benign paroxysmal positional
      vertigo (HSC-BPPV).were symptom-free. OBJECTIVES: To treat patients with
      cupulolithiasis of the HSC-BPPV. SUBJECTS AND METHODS: This was a prospective
      study including 22 subjects with HSC-BPPV (cupulolithiasis) based on apogeotropic
      direction-changing positional nystagmus (apo-DCPN). Patients adopted FPP-one,
      which means lying down on the side of the weaker nystagmus during nightly rest
      for 2 weeks. If apo-DCPN persisted, subjects adopted type two FPP (FPP-two),
      which means lying on the strongest nystagmus side during nightly rest for 2
      weeks. RESULTS: No vertigo or nystagmus was observed in 15 subjects after FPP
      one. One subject experienced geotropic DCPN (geo-DCPN), two subjects had
      posterior BPPV, and another had superior BPPV. Three subjects had persistent apo
      DCPN and they were subjected to FPP-two. After that, no vertigo or nystagmus was
      detected in two subjects. Apo-DCPN persisted in the other remaining subject after
      FPP-two.

PMID- 19863313
TI  - Effect of topical use of mitomycin C and 5-fluorouracil on the closure time of
      myringotomies created by radiofrequency unit.
AB  - CONCLUSION: Both mitomycin C (MC) and 5-fluorouracil (5-FU) had a significant
      effect in prolonging the patency rate of radiofrequency myringotomy. OBJECTIVE:
      To compare the effect of topical use of MC and 5-FU on the closure time of
      myringotomies created by a radiofrequency unit. MATERIALS AND METHODS:
      Myringotomies were performed using a radiofrequency unit on 80 tympanic membranes
      of 40 rats. Rats were divided into two study groups and one control group. MC
      (0.4 mg/ml) and 5-FU (50 mg/ml) pledgets were applied topically in the right ears
      (study groups, 20 ears each) for 10 min and saline pledgets in the left ears
      (control group, 40 ears). Animals were monitored using otomicroscopy weekly and
      patency rates were recorded until myringotomy closure. RESULTS: The mean patency
      times were 4.85 weeks for the MC group and 3.90 weeks for the 5-FU group. The
      mean patency rate for the control side was 1.30 weeks. The log-rank test revealed
      both study groups to have a significantly longer patency time than the control
      group (p<0.0001). Although the patency rate was found to be higher in the MC
      treated group than the 5-FU-treated group, this difference was not statistically
      significant (p>0.05).

PMID- 19863315
TI  - Poly(ADP-ribose) polymerase-1 (PARP-1) longer alleles spanning the promoter
      region may confer protection to bilateral Meniere's disease.
AB  - CONCLUSION: The longer alleles (CA)17-20 of the promoter region of PARP-1 gene
      may confer some protection against bilateral Meniere's disease (BMD). OBJECTIVE:
      To analyze microsatellite (CA)(n) polymorphisms in the promoter region of PARP-1
      gene and seek out risk and protective variants for BMD. SUBJECTS AND METHODS:
      Eighty patients from two ethnically defined groups with definite BMD, according
      to the diagnostic scale of the American Academy of Otolaryngology Head and Neck
      Surgery, were compared with a group of 371 normal controls from the same origin
      in a prospective multicenter study. We developed a specific amplification
      protocol to determine the PARP1-promotor CA microsatellite polymorphisms.
      RESULTS: We found that the longer alleles (CA)17-20 had a very low frequency in
      BMD (2/160, 1.3%, OR=7.33 (1.77-30.37, 95% CI), corrected p=0.012), suggesting
      that it may confer some protection against BMD.

PMID- 19863316
TI  - A head-tilt caloric test for evaluating the vertical semicircular canal function.
AB  - CONCLUSIONS: The caloric test with head-tilt can be used as a tool for assessing
      vertical canal function as an office procedure. OBJECTIVE: Evaluation of vertical
      canal function. PATIENTS AND METHODS: We provoked caloric response by cold water
      in the vertiginous patients in supine position. During the culmination of the
      response we rotated the head 45 degrees from the sagittal plane to place the
      posterior canal to earth-vertical. Thereafter we rotated the head 45 degrees to
      the opposite direction to place the anterior canal to earth-vertical. The eye
      movements were recorded by two-dimensional electronystagmography. The data
      collected from the examination of 100 ears with normal caloric response in
      horizontal component were analyzed. RESULTS: The down-beating vertical component
      intensified when the posterior canal was placed to earth-vertical. The up-beating
      vertical component intensified when the anterior canal was placed to earth
      vertical. These findings suggested that the vertical canals were functioning.

PMID- 19863317
TI  - Wine produced by ecological methods produces relatively little nasal blockage in
      wine-sensitive subjects.
AB  - CONCLUSION: Subjects with self-reported nasal symptoms following consumption of
      red wine may respond with less nasal blockage to a wine produced with ecological
      methods than to wine not labelled as ecologically produced. OBJECTIVE: To compare
      nasal symptoms following intake of three different wines--one that was
      ecologically produced and two that were traditionally produced. SUBJECTS AND
      METHODS: Individuals with self-reported nasal symptoms following consumption of
      red wine were subjected to controlled intake of three different wines in a double
      blinded, randomized, and crossover design. Nasal symptoms and peak nasal
      inspiratory flow (PNIF) were monitored before and 15, 30, 45, and 60 min
      following intake of wine. RESULTS: All wines produced nasal symptoms, notably
      nasal blockage. While blockage scores did not differ between the two non
      ecological wines, the ecological wine was associated with significantly lower
      blockage scores, as compared with both the other wines.

PMID- 19863318
TI  - Value of nasal mucosa congestion index in choosing treatment strategies for
      chronic rhinosinusitis.
AB  - CONCLUSION: The mucosa compliance in lesions is determined by the congestion
      index, enabling us to determine whether the patient is sensitive to
      pharmacotherapy and to choose surgical management rationally. OBJECTIVE: To
      explore the correlation between the nasal mucosa congestion index and tissue
      remodeling in chronic rhinosinusitis (CRS) and to provide objective evidence for
      clinical choice of therapeutic methods. PATIENTS AND METHODS: Forty-four patients
      with CRS who underwent nasal endoscopic surgery were enrolled in the study. The
      congestion indexes of the nasal mucosa were measured using an acoustic rhinometer
      and specimens were taken from the uncinate process mucosa to evaluate vascular
      density and degree of fibrosis. The correlations were statistically analyzed.
      RESULTS: There was an inverse correlation between the congestion index and degree
      of fibrosis (r=- 0.522, p=0.00) and a direct correlation between the congestion
      index and vascular density (r=0.838, p=0.00) in nasal mucosa. There was a
      significant correlation between the congestion index and the combination of
      degree of fibrosis and vascular density with a determination coefficient (R(2))
      of 0.778.

PMID- 19863319
TI  - Expression of p53, p16INK4A, pRb, p21WAF1/CIP1, p27KIP1, cyclin D1, Ki-67 and HPV
      DNA in sinonasal endophytic Schneiderian (inverted) papilloma.
AB  - CONCLUSIONS: Human papilloma virus (HPV) was associated with sinonasal inverted
      papilloma (SIP) in 14/20 (70%) patients with a prevalence of HPV 6/11;
      alterations of the cell cycle proteins were statistically significant.
      OBJECTIVES: We investigated SIPs relationships between HPV infection and aberrant
      expression of cell cycle proteins. MATERIALS AND METHODS: Twenty SIPs were
      evaluated for p53, p16(INK4a), pRb, p21(WAF1), p27(Kip1), cyclin D1 and Ki-67
      expression by immunohistochemistry. HPV was investigated by polymerase chain
      reaction (PCR). RESULTS: HPV DNA was detected in 14/20 patients with inverted
      papillomas (IPs) (70%). The majority of tumours showed strong p16, p21, p27, pRb
      and cyclin D1 staining and little or no p53 expression. Tumours harbouring
      dysplasia were significantly more likely to be p53-positive and exhibit up
      regulated p21 and p27, and showed altered intensity and distribution of reactive
      cells into and through the epithelium. Dysplastic epithelium was strongly
      reactive for p16 and the MIB 1 labelling index was almost 20%. These findings
      were associated with expression of p53 in the same zones. Comparing the p53
      reactivity with the presence of HPV DNA, SIPs were stratified as follows: HPV +
      p53-, 12 (63.15%); HPV + p53+, 2 (10.52%); HPV - p53+, 3 (15.78%) and HPV - p53-,
      2 (10.52%). Statistical analysis showed that HPV presence correlated with p53
      positive immunostaining (p=0.045).

PMID- 19863320
TI  - Effects of short inter-stimulus intervals on olfactory and trigeminal event
      related potentials.
AB  - CONCLUSION: Chemosensory event-related potentials (CSERPs) were identified in all
      measurements using the 20 s and the 10 s inter-stimulus interval (ISI) protocol,
      reducing the recording time to 75% or 57% compared with the standard protocol. A
      possible explanation for the rising CSERP amplitudes by shortening the ISI in
      CO(2) stimulation is due to a phenomenon known as trigeminal sensitization during
      repeated stimulation. OBJECTIVES: CSERPs are influenced by the ISI. The aim of
      this study was to evaluate the changes in CSERPs by decreasing the ISI from 30 s
      to 20 s or 10 s, respectively. SUBJECTS AND METHODS: Ten normosmic healthy
      subjects participated this study. Phenyl ethyl alcohol (PEA), hydrogen sulphide
      (H(2)S) and carbon dioxide (CO(2)) were used in CSERP measurements with different
      ISI protocols (30 s (standard), 20 s and 10 s). Amplitudes and latencies of ISI
      protocols were submitted to ANOVA for repeated measurements and t tests for
      paired samples. RESULTS: The amplitudes of CSERPs with PEA and H(2)S stimuli were
      decreasing with shortening the ISI significantly. In contrast, the highest
      amplitudes of trigeminal CSERPs were recorded with the 10 s ISI protocol with
      CO(2). The ANOVA revealed a significantly different effect of shortening the ISI
      on CSERPs on the right and the left side.

PMID- 19863321
TI  - Effects of topical drops and sprays on mucociliary transport time and nasal air
      flow.
AB  - CONCLUSION: This study revealed that the nasal topical drops, which could be
      purchased without a proper prescription, should not be used randomly and non
      selectively. OBJECTIVE: To investigate the effect of nasal drops and sprays on
      the nasal air flow and mucociliary transport time (MTT) in healthy volunteers
      with no septal deviation and no history of frequent upper respiratory infection.
      SUBJECTS AND METHODS: Saline, fluticasone propionate drops and sprays, mometasone
      furoate, budesonide, xylometasoline chloride, fusafungine spray, Ringer's lactate
      and sea water were selected as the agents to be investigated. Volunteers were
      subdivided into two subgroups according to their rhinomanometric scores: group 1
      consisted of subjects with nasal respiration > or =500 ml at 150 daPa and group 2
      consisted of those with nasal air flow <500 ml. RESULTS: No statistically
      significant difference was found among the effects of these agents on MTT in
      group 1. In group 2, xylometasoline chloride, fluticasone propionate spray and
      sea water sprays prolonged the MTT. When the rhinomanometric scores at 150 daPa
      were assessed, use of xylometasoline chloride, fluticasone propionate drops,
      budesonide, fusafungine, sea water and Ringer's lactate were found to diminish
      the nasal air flow with respect to normal values in group 1. In group 2, no
      significant difference was noticed between normal values and values acquired
      after use of nasal drops. Comparing the same agents, we did not find a
      significant difference between groups 1 and 2 regarding MTT and nasal air flow.

PMID- 19863322
TI  - Cytology of the nasal mucosa after total laryngectomy.
AB  - CONCLUSION: This study demonstrates morphological changes in the nasal mucosa as
      a consequence of functional changes of the nasal cavity after total laryngectomy
      (TLE). OBJECTIVE: Observation of the changes of the nasal mucosa in patients
      after TLE. PATIENTS AND METHODS: A cohort observational study contained 30
      patients after TLE. These patients underwent nasal endoscopy and cytological and
      microbiological examination of the nasal mucosa. The control group comprised 30
      patients. RESULTS: In patients who underwent TLE, morphological changes occurred
      in the nasal mucosa. The hyperplasia of the cells in the basal zone was the most
      remarkable change after TLE. The difference was statistically significant
      (p=0.0002) in comparison with the control group. No statistically significant
      difference was shown in the incidence of squamous cell metaplasia. The
      inflammatory changes in the nasal mucosa were found in only 10% of patients after
      TLE; in comparison with the control group the statistically significant decrease
      was proven (p=0.003). The presence of bacteria in the nasal mucosa without any
      signs of inflammation was demonstrated in 27% of the patients who underwent TLE.
      That finding was not seen in the control group. The statistically significant
      difference was demonstrated (p=0.0046).

PMID- 19863323
TI  - Surgical intervention represents a feasible option for patients with mild
      obstructive sleep apnoea.
AB  - CONCLUSIONS: Patients with mild obstructive sleep apnoea (OSA) depict the disease
      as being detrimental to their health, causing significant symptoms. These
      patients were found to achieve significant improvements in OSA-related symptoms
      after surgical intervention. OBJECTIVES: Although the effects of surgical
      treatment on OSA have been encouraging in many previous studies, little is known
      about its effects in patients with mild OSA. The aim of our study was to assess
      the evolution of symptoms experienced by mild OSA patients after surgical
      intervention. SUBJECTS AND METHODS: This was an observational follow-up study in
      a university hospital in Finland. The change in daytime and night-time symptoms
      was assessed by a standardized questionnaire before treatment and after a mean
      follow-up time of 3 years in both operative and control groups in 81 adult
      patients with mild OSA. RESULTS: At the follow-up, the control group experienced
      significantly more daytime sleepiness (p<0.001) compared with the operative
      group. Adjusted odds ratio (OR) for daytime sleepiness was 0.05 (95% CI 0.01
      0.25, p<0.001) in operatively treated patients as compared with control patients,
      with improvement of witnessed apnoeas (p<0.001) and sleep quality (p=0.033). The
      OR for intensive snoring was 0.06 (95% CI 0.02-0.22) in the operative group as
      compared with the control group.

PMID- 19863324
TI  - Surgical management of retropharyngeal abscesses.
AB  - CONCLUSION: Retropharyngeal abscess (RPA) is a rare, potentially life-threatening
      disease, requiring appropriate otorhinolaryngologic as well as radiologic
      diagnostics, and medical and surgical intervention by a transoral, transcervical
      or transnasal approach in a multidisciplinary setting. OBJECTIVES: The risks and
      benefits of surgical intervention in patients with RPA were assessed. The main
      outcome measure was the clinical resolution of the abscess. PATIENTS AND METHODS:
      A retrospective chart review was performed at a tertiary care university hospital
      over a period of 28 months. Eleven patients aged 1 to 68 years with the diagnosis
      of RPA were included. RESULTS: All patients presented with restricted cervical
      mobility and all patients had CT and/or MRI scan on admission. The mean abscess
      volume was 9.4 cm(3). Surgical intervention was performed in all cases, including
      transoral (n=5), transcervical (n=3) or combined transoral and transcervical
      (n=2) drainage. In one patient RPA close to the skull base was drained by an MRI
      guided transnasal approach. All patients recovered; however, there was one
      recurrence and in one case surgical tracheotomy was unavoidable during the course
      of disease. Growth of streptococcal species was verified in six of the examined
      abscesses. Abscessing lymphadenitis, infection of a cervical cyst, and previous
      ganglionar local opioid analgesia treatment were identified as causative factors.

PMID- 19863325
TI  - Uvulopalatopharyngoplasty in 158 OSAS patients failing non-surgical treatment.
AB  - CONCLUSIONS: Uvulopalatopharyngoplasty (UPPP) in patients with obstructive sleep
      apnoea syndrome (OSAS) who had failed treatment with continuous positive airway
      pressure (CPAP) and mandibular retaining device (MRD) was effective and safe. The
      satisfaction rate was high. We recommend UPPP in selected OSAS patients,
      especially younger patients. OBJECTIVES: To evaluate the efficacy and
      complication rate of UPPP. PATIENTS AND METHODS: This was a non-randomized
      prospective study of 139 men and 19 women, median age 45 years (range 20-75),
      median body mass index (BMI) 29 (range 20-48), who underwent UPPP. One year
      follow-up comprised ambulant sleep apnoea recordings and questionnaires with the
      Epworth Sleepiness Scale (ESS). RESULTS: In all, 76% of the patients underwent
      sleep recordings preoperatively and postoperatively. The oxygen desaturation
      index (ODI(4)) decreased from median 23 (range 6-100) to 8 (range 0-60), p<0.001.
      Criteria of success (>50% reduction and ODI<20), was 64%. The ESS value decreased
      from median 12 (range 0-21) to 6 (0-22), p<0.001. In all, 88% of the patients
      were satisfied. Four of 158 patients (2.5%) had serious postoperative
      complications. There was neither sequel of complications nor mortality.

PMID- 19863326
TI  - Outcomes of type II thyroplasty for adductor spasmodic dysphonia: analysis of
      revision and unsatisfactory cases.
AB  - CONCLUSION: The factors responsible for the observed failures can be broken into
      two major groups: (1) a wrong indication and (2) an inadequate technique to
      achieve relief from an excessively tight glottal closure. The use of a titanium
      bridge in place of a silicone shim was found to be essential. Type II thyroplasty
      can relieve the symptoms of adductor spasmodic dysphonia (AdSD) when implemented
      with a modern technique using titanium bridges. OBJECTIVES: To identify the
      factor or factors that necessitated revision surgery in type II thyroplasty for
      AdSD, detailed analytical examinations were made of individual cases with
      unsatisfactory outcomes. PATIENTS AND METHODS: A retrospective analysis of a case
      series with follow-up periods of 2-5 years. RESULTS: Ninety AdSD patients
      underwent type II thyroplasty. The results in one patient were limited because a
      pathological mechanism other than AdSD was also involved. One patient, a singer,
      who wanted a more intense voice for singing was dissatisfied with the results. In
      three patients, the material used for fixation was inadequate. In two other
      patients, the method of application of the fixative material was found to be
      insufficient as it did not include both the upper and lower sides.

PMID- 19863327
TI  - Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients.
AB  - CONCLUSIONS: Weekly paclitaxel may be an active and well tolerated chemotherapy
      regimen for patients with platin-resistant advanced head and neck cancer.
      OBJECTIVES: Weekly paclitaxel should be an active and well tolerated regimen for
      palliative treatment of platin-resistant patients with recurrent or metastatic
      carcinoma of the head and neck. We analyzed the antitumor activity and toxicity
      profile. PATIENTS AND METHODS: Sixty consecutive patients with advanced head and
      neck cancer were treated with 1 h infusion of paclitaxel, 80 mg/m(2) weekly, for
      6 consecutive weeks. Patients who showed disease response or disease
      stabilization continued until progression of disease. RESULTS: A total of 719
      doses of paclitaxel were administered to the 60 patients. No complete response
      was observed. Partial response and stable disease were observed in 26 (43.3%) and
      9 (15%) patients, respectively. Median time to tumor progression for patients who
      responded to therapy was 6.2 months (SD=1.3; 95% CI, 3.7-8.6) and the overall
      median survival in this group of patients was 8.5 months (SD=1.4; 95% CI, 5.7
      11.2). The main toxic effects were leukopenia (26.6%), anemia (43.3%), fatigue
      (37.4%), alopecia (18.7%), rash/desquamation (13.3%), and thrombophlebitis
      (6.8%).

PMID- 19863328
TI  - Sleep apnoea in patients after treatment of head neck cancer.
AB  - CONCLUSIONS: The prevalence of sleep apnoea among patients following treatment of
      head and neck carcinomas seems to be slightly higher than in the normal
      population. The possible importance of tumour treatment features, especially
      transient tracheostoma, needs further assessment. OBJECTIVES: The epidemiology of
      sleep apnoea in patients following the treatment of head and neck cancer remains
      unclear. This study was undertaken to assess the prevalence of sleep apnoea in
      head and neck cancer patients by characterizing their clinical, anatomical and
      tumour treatment features. PATIENTS AND METHODS: Our study examined 31 patients
      in a prospective non-controlled study using a standardized questionnaire that
      included the Epworth Sleepiness Scale (ESS) and a polygraph. RESULTS: Six of the
      31 patients showed a pathologic AHI > or = 20/h. Subjects positive for sleep
      apnoea more often had a tumour of the hypopharynx or larynx and more often had a
      transient tracheostoma during cancer therapy. Radiotherapy had no clear impact on
      the prevalence of sleep apnoea.

PMID- 19863329
TI  - Identification of epidermal growth factor receptor (EGFR) exon 20 single
      nucleotide polymorphism in Chinese squamous cell carcinoma of head and neck
      (SCCHN).
AB  - CONCLUSION: The 78th single nucleotide polymorphism (SNP) in exon 20 of epidermal
      growth factor receptor (EGFR) might be a predictor of the clinical course of
      squamous cell carcinoma of the head and neck (SCCHN), and genetic predisposition
      could influence the progression of SCCHN in Chinese subjects. OBJECTIVE: To
      analyze the clinical significance of EGFR SNP in Chinese SCCHN patients.
      MATERIALS AND METHODS: Direct sequencing of exons 18-21 was used to analyze
      somatic mutations of EGFR. Reverse transcriptase polymerase chain reaction (RT
      PCR) was used to evaluate the expression level of EGFR. The chi-square test and
      Kaplan-Meier method were the main statistical methods used to analyze the
      correlation of the investigated variables and prognostic significance. RESULTS:
      In analyzing exons 18-21 of EGFR in 96 patients with SCCHN, only one SNP was
      found in the 78th site of exon 20 and it mostly existed in specimens coming from
      the hypopharynx. Further statistical analysis showed that among the clinical or
      histopathologic parameters, the 78th SNP had a close relationship with earlier
      stage and more localized primary carcinoma, while at present the analysis did not
      support the proposition that the SNP was an independent prognostic factor.

PMID- 19863330
TI  - Prognostic factors for squamous cell carcinoma of the temporal bone: extensive
      bone involvement or extensive soft tissue involvement?
AB  - CONCLUSION: Extensive bone erosion correlated with a worse prognosis of the
      squamous cell carcinoma (SCC) of the temporal bone but extensive soft tissue
      involvement did not correlate with prognosis in this study. Resectability of the
      tumor seems to be major prognostic factor of temporal bone SCC. OBJECTIVE:
      Prognostic factors for SCC of the temporal bone were evaluated regarding initial
      clinical symptoms and radiographic imaging. PATIENTS AND METHODS: Clinical
      symptoms of the patients with primary SCC of the external auditory canal (EAC) or
      middle ear (ME) were reviewed based on medical records. Correlation of clinical
      symptoms and cancer severity staging using the modified Pittsburgh classification
      was analyzed, along with disease-specific survival (DSS). RESULTS: Sixteen
      patients with primary SCC of the EAC (n=13) or ME (n=3) were included in the
      study population. DSS was not influenced by whether a hearing disturbance or
      otalgia was noted at the first medical examination. Extended bone involvement
      identified with imaging studies significantly correlated with worse prognosis
      (p<0.05). Prognoses of patients without extensive bone erosion were good, and
      extensive (> or =0.5 cm) soft tissue involvement did not correlate with prognosis
      in this study. Prognoses of patients with insufficient bone resection or no
      surgery were significantly poor (p<0.01).

PMID- 19863332
TI  - Endolymphatic hydrops and therapeutic effects are visualized in 'atypical'
      Meniere's disease.
AB  - A 53-year-old male with fluctuating low frequency sensorineural hearing loss and
      tinnitus, but without vertigo, was evaluated by MRI obtained by intratympanic
      injection of a gadolinium-based contrast agent (GBCA) before and after the
      administration of isosorbide. The endolymphatic hydrops was semi-quantitatively
      evaluated by a 3.0-T MR scanner. For quantification, the affected
      side/contralateral side ratios were calculated. A gadodiamide (a kind of GBCA)
      enhanced space surrounding the endolymph in the affected side with a 0.50 ratio
      (which may have represented endolymphatic hydrops) improved after isosorbide
      therapy to a 0.98 ratio. Thus, endolymphatic hydrops was demonstrated in a
      patient with 'atypical' Meniere's disease (MD), suggesting that at least some
      atypical MD may share similar etiology with, and therefore be a continuum of, MD.
      Also, therapeutic effects could be visualized by using MRI. Therefore, MRI-based
      diagnosis of MD-related disease will be a powerful tool not only because of its
      precision but also its usefulness for therapeutic evaluation.

PMID- 19863331
TI  - Clinical and pathological analysis of malignant carotid body tumour: a report of
      nine cases.
AB  - CONCLUSIONS: Malignant carotid body tumour (MCBT) is a clinically rare disease
      that often invades the carotid artery and cranial nerves. Diagnosis of malignant
      tumour should be based on extensive invasion of neighbouring organs and distant
      metastasis. Extensive resection should be undertaken early. Radiotherapy is
      effective, whereas chemotherapy is uncertain. OBJECTIVE: To summarize the
      clinical pathological and prognostic characteristics of MCBT and explore methods
      for diagnosis and treatment. MATERIALS AND METHODS: The study material comprised
      clinical, pathological, therapeutic and follow-up data concerning nine patients
      (four males, five females) with MCBT, treated at Tianjin Cancer Hospital between
      January 1956 and June 2006. The material was analysed retrospectively. Disease
      duration averaged 6.4 years. Shamblin classification was: one case, type II; 8
      cases, type III. All nine patients underwent ultrasound examination, four
      underwent digital subtraction arteriography (DSA) and three had magnetic
      resonance angiography (MRA). Five patients underwent preoperative training of
      compression of the carotid (Matas test). Extensive resection was performed in all
      nine cases. RESULTS: The carotid artery was blocked in three patients. In one of
      these the artery was reconstructed with a vascular prosthesis, while two
      underwent carotid ligation. Eight patients suffered from a cranial nerve
      dysfunction (defect) and two suffered postoperatively from a hoarse voice, four
      had a glossal deviation, five had Horner's syndrome and one had a deviation of
      the lip angle. One patient had a congestive cough. The histopathological
      diagnosis in all nine cases was MCBT. One patient had metastases to a cervical
      lymph node and lung and another had liver metastasis. The median follow-up period
      was 3 years (range 6 months to 14 years). Six patients survived surgery, of whom
      two underwent radiotherapy. Two patients died and one could not be traced.

PMID- 19863333
TI  - Neural response thresholds in the Nucleus Contour cochlear implant before and
      after stylet removal.
AB  - CONCLUSION: The study shows that there are differences in the measurement of the
      action potentials with and without the stylet in the Nucleus Freedom Contour
      Advance that are higher in the apex than in the base of the cochlea. OBJECTIVES:
      To determine if there are differences in the intraoperative impedances and in the
      neural response telemetry threshold values in the Nucleus Freedom Contour Advance
      before and after stylet removal. SUBJECTS AND METHODS: This was a prospective
      clinical study. Intraoperative impedances and neural response telemetry in users
      of the Freedom Contour Advance Cochlear Implant were measured before and after
      stylet removal. RESULTS: There was a significant reduction in the impedance
      values of an average 1.5 kOmega+/-2.3 in common ground mode and 1.3 kOmega+/-2.3
      for all monopolar modes after the stylet removal (p < 0.001). When analyzing the
      apical, medium, and basal electrodes, there was a statistically significant
      reduction in the neural response thresholds after stylet removal only in the
      apical electrodes (p = 0.001).

PMID- 19863334
TI  - Interferon: does it still have a role in the 21st century?

PMID- 19863335
TI  - Iron overload, hematopoietic cell transplantation, and graft-versus-host disease.
AB  - Many patients who undergo hematopoietic cell transplantation (HCT) present with
      anemia and have received red blood cell transfusions before HCT. As a result,
      iron overload is frequent and appears to be particularly prominent in patients
      with myelodysplastic syndromes. There is evidence that peritransplant events
      contribute to further iron accumulation, although the mechanism that disrupts
      normal iron homeostasis remains to be determined. Recent studies suggest that
      iron overload, as determined by ferritin levels, a surrogate marker for iron, is
      a risk factor for increased non-relapse mortality after HCT. Iron overload is
      associated with an increased rate of infections, in particular with fungal
      organisms. Furthermore anecdotal data suggest that increased hepatic iron may
      mimic the clinical picture of (chronic) graft-versus-host-disease (GVHD). Whether
      excess iron contributes to GVHD and whether iron depletion, be it by phlebotomy
      or chelation, reduces the post-transplantation complication rate and improves
      transplant outcome is yet to be determined.

PMID- 19863336
TI  - Fludarabine followed by alemtuzumab consolidation for previously untreated
      chronic lymphocytic leukemia: final report of Cancer and Leukemia Group B study
      19901.
AB  - The humanized anti-CD52 monoclonal antibody alemtuzumab is an effective therapy
      for chronic lymphocytic leukemia (CLL). We examined the impact of alemtuzumab
      treatment after initial fludarabine treatment for feasibility and safety.
      Patients (N = 85) with previously untreated symptomatic CLL received fludarabine
      (25 mg/m(2)/day) for 5 days every 4 weeks for four cycles followed by 2 months of
      observation. Patients with stable disease or better response then received
      alemtuzumab 30 mg three times weekly for 6 weeks either intravenously (IV; cohort
      1; N = 39) or subcutaneously (SC; cohort 2; N = 20). Of the 85 evaluable patients
      enrolled on our study, four (5%) attained a complete response (CR) and 43 (51%)
      attained a partial response after fludarabine induction for an overall response
      rate (ORR) of 55%. Thirty-nine patients received IV alemtuzumab for consolidation
      with improvement in CR to 27% and ORR to 73%. Twenty patients received SC
      alemtuzumab consolidation with improvement in CR to 17% and ORR to 69%. Toxicity
      from IV alemtuzumab included infusion-related reactions and infection. Mild local
      inflammation was common from SC alemtuzumab but there were virtually no systemic
      side effects. Nine of 59 (15%) patients had cytomegalovirus (CMV) infections; one
      patient died. The administration of alemtuzumab as consolidation therapy
      following an abbreviated fludarabine induction is feasible but requires close
      monitoring for CMV infection and other infectious events.

PMID- 19863337
TI  - p53 expression by immunohistochemistry is an important determinant of survival in
      patients with chronic lymphocytic leukemia receiving frontline chemo
      immunotherapy.
AB  - Although chromosome 17p abnormalities and TP53 mutations have been reported as
      poor prognostic indicators in chronic lymphocytic leukemia (CLL), the impact of
      aberrant p53 expression as assessed by immunohistochemistry (p53-IHC) has not
      been defined in patients with CLL treated with chemoimmunotherapy, particularly
      in the context of other novel markers such as ZAP-70 expression and IgVH mutation
      status (IgVH MS). We assessed p53-IHC in 222 bone marrow (BM) specimens from
      patients with CLL enrolled in a phase II trial with fludarabine,
      cyclophosphamide, and rituximab (FCR). ZAP70 expression and IgVH MS were assessed
      in 208 and 108 patients, respectively. One hundred sixty-eight patients had
      concurrent classical cytogenetic analysis. p53-IHC correlated with abnormal
      karyotype (p = 0.002) and adversely affected overall survival independent of
      ZAP70 expression and IgVH MS (p < 0.001). Patients with p53-IHC(+) CLL were less
      likely to achieve complete remission, but patients who did achieve complete
      remission showed a durable response. In this patient cohort, p53-IHC is an
      important determinant of complete remission and overall survival, but not
      remission duration, in patients with CLL receiving FCR.

PMID- 19863338
TI  - Radiation therapy compared with chemotherapy for consolidation of chemotherapy
      induced remission of advanced Hodgkin lymphoma: a study by the Eastern Co
      operative Oncology Group (E1476) with >20 years follow-up.
AB  - MOPP-Bleo (nitrogen mustard, vincristine, procarbazine, prednisone and bleomycin)
      induction therapy was given to 253 evaluable patients with Hodgkin lymphoma,
      stages IIIB, III(s), or IV. Complete response (CR) occurred in 145 patients (57%)
      and partial response (PR) in 93 (37%). Of those 238 responders, 178 were
      randomized to consolidation therapy, and 164 were eligible and analyzable,
      including 114 CRs [55 patients randomized to ABVD and 59 to radiation therapy
      (RT)] and 50 partial responders (PRs) (25 each randomized to ABVD and RT). Among
      the 50 patients with PR, 34 (68%) converted to CR (16 with ABVD and 18 with RT).
      Therefore, of 253 patients, 182(72%) achieved CR and 56 (22%), PR. Median follow
      up for all patients is 22.3 years and the estimated overall survival (OS) rate at
      20 years is 48%. Of the 148 eligible, analyzable patients with CR, the estimated
      proportion remaining in CR at 20 years is 62%. OS at 20 years was significantly
      greater for patients receiving ABVD consolidation (66%) when compared with those
      who received RT consolidation (43%) (p = 0.002). Treatment toxicity was
      acceptable. After MOPP-Bleo induction for advanced Hodgkin lymphoma, ABVD
      provides better consolidation than local RT.

PMID- 19863339
TI  - Multicentric plasmocytic Castleman's disease with polyneuropathy, organomegaly,
      endocrinopathy, M protein, skin changes syndrome and coexistent human herpes
      virus-6 infection--a possible relationship.
AB  - Authors report a case of Castleman's disease (CD) with polyneuropathy,
      organomegaly, endocrinopathy, M protein, skin change (POEMS) syndrome. According
      to the present knowledge, these two rare conditions are often induced by Human
      Herpes Virus- 8 (HHV-8) or by Human Immunodefeciency Virus, separately or in
      combination. In this case, however, HHV-6 viral DNA had been detected in the
      blood and lymph node samples by PCR. The authors conclude that the modulation of
      immune functions by HHV-6 might be responsible for the development of CD and
      POEMS syndrome in the referred case.

PMID- 19863340
TI  - Influence of the polymorphism in candidate genes on late cardiac damage in
      patients treated due to acute leukemia in childhood.
AB  - Anthracyclines have contributed significantly to the increased cure rate in
      pediatric oncology. Cardiac toxicity is an important late effect after
      anthracycline treatment and is thought to occur by reactive oxygen species
      mediated cardiac damage. We hypothesized that deactivating variants of superoxide
      dismutase II (SOD2) [rs4880 (-9Val > Ala)], catalase (CAT) [rs1001179 (-262C > T)
      and rs10836235 (c.66 + 78C > T)], GSTT1, and GSTM1 may increase the risk of
      developing cardiac toxicity, in patients exposed to anthracyclines. The
      hypothesis was tested in a cohort of 76 long-term survivals of acute
      lymphoblastic leukemia in childhood. Cardiac damage was evaluated as an
      attributive variable and compared to gene polymorphisms. In our study group, we
      show statistically significant correlation between CC homozygosity for CAT
      (rs10836235 (c.66 + 78C > T)) and cardiac damage after anthracycline exposure (p
      = 0.020). We found no statistically significant correlation between cardiac
      damage after anthracycline exposure and deactivating variants of SOD2 [rs4880 (
      9Val > Ala)], CAT [rs1001179 (-262C > T), GSTT1, and GSTM1.

PMID- 19863341
TI  - Functional signatures identified in B-cell non-Hodgkin lymphoma profiles.
AB  - Gene-expression profiling in B-cell lymphomas has provided crucial data on
      specific lymphoma types, which can contribute to the identification of essential
      lymphoma survival genes and pathways. In this study, the gene-expression
      profiling data of all major B-cell lymphoma types were analyzed by unsupervised
      clustering. The transcriptome classification so obtained, was explored using gene
      set enrichment analysis generating a heatmap for B-cell lymphoma that identifies
      common lymphoma survival mechanisms and potential therapeutic targets,
      recognizing sets of coregulated genes and functional pathways expressed in
      different lymphoma types. Some of the most relevant signatures (stroma, cell
      cycle, B-cell receptor (BCR)) are shared by multiple lymphoma types or
      subclasses. A specific attention was paid to the analysis of BCR and coregulated
      pathways, defining molecular heterogeneity within multiple B-cell lymphoma types.

PMID- 19863342
TI  - Donor-derived hairy-cell leukemia.

PMID- 19863343
TI  - CD56-negative extranodal nasal type of natural killer/T-cell lymphoma with
      extranasal skin involvement.

PMID- 19863344
TI  - Expression of progranulin (Acrogranin/PCDGF/Granulin-Epithelin Precursor) in
      benign and malignant ovarian tumors and activation of MAPK signaling in ovarian
      cancer cell line.
AB  - It has been recently demonstrated that progranulin is overexpressed in ovarian
      cancer and that this protein is involved in the stimulation of cell
      proliferation, malignancy, and chemoresistance in ovarian cancer. The goal of the
      present study was to establish the differences in progranulin expression among
      normal, benign, and malignant ovarian tissues and to identify the signal
      transduction pathways activated by progranulin in an ovarian cancer cell line.
      Compared with benign tumors and normal ovarian tissue, progranulin mRNA and
      protein were overexpressed in malignant tumors. Survival analysis by the Kaplan
      Meier method showed a correlation between high mRNA expression levels with poor
      survival outcome. Progranulin activated the MAPK-signaling pathway in NIH-OVCAR-3
      cells. Progranulin expression may be potentially involved in the pathogenesis and
      malignant progression of ovarian cancer, and thus may represent a therapeutic
      target for this particular malignancy.

PMID- 19863345
TI  - A structured review and guide through studies on health-related quality of life
      in kidney cancer, hepatocellular carcinoma, and leukemia.
AB  - Aim of this paper is to review and describe Health-Related Quality of Life
      (HRQoL) measures applied in kidney cancer, hepatocellular carcinoma, and leukemia
      patients under drug therapy. A comprehensive search in PubMed was conducted to
      identify studies assessing quality of life (QoL) in these indications. In total
      32 studies, including four studies through reference list checking and 21
      different HRQoL instruments, were identified. Six generic, five disease-specific,
      and 10 domain-specific instruments were identified. In conclusion no overall
      standards in HRQoL measurement could be observed in the respective indications.

PMID- 19863346
TI  - Management of anaemia in prostate cancer.
AB  - Anaemia is a frequent complication of prostate cancer and of its treatments. In
      Europe prostate cancer accounts for the 10.8% of all malignant neoplasms.
      Iatrogenic hypogonadism and age-related physiologic changes along with
      nutritional deficits contribute to increase prevalence of prostate cancer related
      anaemia. The reason of the present review is to provide clinicians with all
      aspects of a frequent and multifactorial co-morbidity, whose effects are often
      underestimated. Erythropoiesis pathology and causes of anaemia in prostate cancer
      are reviewed. Critical issues of clinical management of anaemia in prostate
      cancer are discussed.

PMID- 19863348
TI  - Augmentation of radiation-induced apoptosis by ellagic acid.
AB  - This study evaluates the potential of ellagic acid (EA) as an enhancer of
      radiation-induced apoptosis in cancer cells. HeLa cells treated with EA and gamma
      radiation showed increased superoxide generation, upregulated p53 protein
      expression, and decreased antioxidant enzymes. We also found that EA and
      radiation enhance capase-3 activity via oxidative stress, increased intracellular
      calcium levels, and phospholipase C and cause a drop in mitochondrial potential.
      These results might provide a basis for prominent reduction of cancer cell using
      EA as an adjunct to radiotherapy and an opportunity to lower the toxic radiation
      doses to improve the quality of life.

PMID- 19863349
TI  - Sodium butyrate increases expression of the coxsackie and adenovirus receptor in
      colon cancer cells.
AB  - Histone deacetylase inhibitors (HDACI), e.g., sodium butyrate (NaB), have been
      suggested to upregulate the coxsackie and adenovirus receptor (CAR). Its impact
      on CAR in colon carcinomas, however, is poorly understood. NaB treatment of colon
      cancer cells increased CAR expression preferentially in cell lines with low basic
      CAR levels. These findings suggest that downregulation of CAR gene expression is
      mediated by transcriptional regulation and that activation of the CAR gene
      promoter is modulated by histone acetylation. The employment of HDACI may,
      therefore, represent a promising approach for improving adenovirus-based
      therapies of colon cancers with low CAR expression levels.

PMID- 19863350
TI  - Possible risk modification by polymorphisms of estrogen metabolizing genes in
      familial breast cancer susceptibility in an Indian population.
AB  - This case control study investigated whether polymorphisms of estrogen
      metabolizing genes CYP1A1 MspI, CYP17 MspAI, COMT Val(158) Met, and SULT1A1
      Arg(213) His have any role in familial breast cancer susceptibility risk.
      Logistic regression analysis adjusted to age was used to calculate odds ratios
      (ORs) and 95% confidence intervals (95%CIs). Familial breast cancer risk due to
      CYP1A1 wt/m1 and m1/m1 genotypes was 2.3 (1.51-3.61)-fold and 7.1 (3.69-13.7)
      fold, respectively. In addition to the main effects, certain first-order
      interactions were also significantly associated with familial breast cancer. Our
      results favor a possible risk modification by estrogen metabolizing gene
      polymorphisms in familial breast cancer susceptibility.

PMID- 19863351
TI  - Effects of naturally occurring polymethyoxyflavonoids on cell growth, p
      glycoprotein function, cell cycle, and apoptosis of daunorubicin-resistant T
      lymphoblastoid leukemia cells.
AB  - Effects of polymethoxyflavonoids tangeretin and nobiletin and the related
      polyphenolic compounds baicalein, wogonin, quercetin, and epigallocatechin
      gallate on the cell growth, P-glycoprotein function, apoptosis, and cell cycle of
      human T lymphoblastoid leukemia MOLT-4 and its daunorubicin-resistant cells were
      investigated. The IC50 values of these compounds on the cell growth were 7.1-32.2
      micromol/L, and the inhibitory effects were observed to be almost equal to the
      parent MOLT-4 and the daunorubicin-resistant cells. Tangeretin and nobiletin
      showed the strongest effects with the IC50 values of 7.1-14.0 micromol/L. These
      polymethoxyflavonoids inhibited the P-glycoprotein function and significantly
      influenced the cell cycle (p<.05), whereas they did not induce apoptosis.

PMID- 19863354
TI  - Hearing status, need for recovery after work, and psychosocial work
      characteristics: results from an internet-based national survey on hearing.
AB  - The main aim of the study is to address the relationship between hearing status
      and need for recovery. In addition, the role of hearing status in the
      relationship between psychosocial work characteristics (i.e. job demands and job
      control) and need for recovery was assessed. The sample comprised 925 normally
      hearing and hearing-impaired working adults (aged 18-65 years) participating in
      the National Longitudinal Study on Hearing. Hearing status was determined using
      the national hearing (speech-in-noise) test over the internet. Psychosocial work
      characteristics and need for recovery were assessed using the job content
      questionnaire and the Dutch questionnaire on the experience and assessment of
      work. Regression models revealed a significant association between hearing status
      and need for recovery after work, poorer hearing leading to an increasing need
      for recovery. Additionally, poorer hearing led to a higher odds for risky levels
      of need for recovery. Hearing status did not influence the significant
      relationship between psychosocial work characteristics (i.e. job demand and job
      control) and need for recovery after work. Implications for clinical practice,
      such as the necessity of having adequate enablement programs for this specific
      group of patients, are discussed.

PMID- 19863355
TI  - Brazilian young adults and noise: attitudes, habits, and audiological
      characteristics.
AB  - The objective of this study was to examine behaviors and attitudes of Brazilian
      teenagers towards noise, and determine their audiological characteristics.
      Participants were 245 young persons (14 to 18 years old) who attended private
      school. Behaviors and attitudes were measured using the validated Portuguese
      version of the Youth Attitude to Noise Scale (YANS). Pure-tone audiometry was
      used to evaluate the hearing of a sub-sample of 24 participants. Music played
      through personal media players was the most common exposure reported. A
      substantial percentage of participants reported temporary tinnitus (69%) after
      attending discos, music concerts, and listening to music through headphones.
      Tinnitus complaints were more frequent among females (41%) than males (27%). Four
      participants (1.6%) reported use of a hearing protector. Among a subsample of 24
      participants, two (8%) young women had bilateral audiometric notches. YANS scores
      in the present study were slightly lower than those obtained in Sweden and the
      US, indicating a more negative attitude towards noise. Gender, age, country,
      and/or region are variables that will influence exposure to noise or music and
      possibly hearing outcomes.

PMID- 19863356
TI  - Assessing speech perception in young children and relationships with language
      skills.
AB  - Few materials are available to assess speech perceptual skills in young children
      without hearing impairments. However, children with a range of developmental
      conditions are at risk of speech discrimination deficits. Tasks that reliably
      assess speech perception skills are thus necessary for research and clinical
      practice. The development and application of two speech perception tests are
      described. Data were collected from 105 children, aged 4-5 years, attending
      mainstream schools, on two tasks, mispronunciation detection and non-word XAB, in
      quiet and in a background of multi-talker babble. Children's receptive language
      skills were also measured. Performance on mispronunciation detection was
      significantly better than on the XAB non-word task, and significantly better in
      quiet than in babble. Performance significantly improved with age, and speech
      discrimination was significantly related to receptive language abilities. Scores
      obtained in quiet and in babble were highly correlated and findings suggest there
      may be no advantage to testing in noise, except to avoid ceiling effects on
      performance. These tasks prove useful in the assessment of young children who may
      have speech discrimination deficits.

PMID- 19863360
TI  - Constant work rate exercise testing: a tricky measure of exercise tolerance.

PMID- 19863361
TI  - Effect of fluticasone propionate/salmeterol (250/50) on COPD exacerbations and
      impact on patient outcomes.
AB  - Prevention and treatment of COPD exacerbations are recognized as key goals in
      disease management. This randomized, double-blind, parallel-group, multicenter
      study evaluated the effect of fluticasone propionate/salmeterol 250 mcg/50 mcg
      (FSC 250/50) and salmeterol 50 mcg (SAL) twice-daily on moderate/severe
      exacerbations. Subjects received treatment with FSC 250/50 during a one month run
      in, followed by randomization to FSC 250/50 or SAL for 52 weeks. Moderate/severe
      exacerbations were defined as worsening symptoms of COPD requiring antibiotics,
      oral corticosteroids and/or hospitalization. In 797 subjects with COPD (mean
      FEV(1) = 0.98L, 34% predicted normal), treatment with FSC 250/50 significantly
      reduced the annual rate of moderate/severe exacerbations by 30.4% compared with
      SAL (1.10 and 1.59 per subject per year, respectively, p < 0.001), the annual
      rate of exacerbations requiring oral corticosteroids by 34% (p < 0.001) and the
      annual rate of moderate/severe exacerbations requiring hospitalization by 36% (p
      = 0.043). Clinical improvements observed during run-in treatment with FSC 250/50
      were better maintained over 52 weeks with FSC 250/50 compared to SAL.
      Statistically significant reductions in albuterol use, dyspnea scores, and
      nighttime awakenings and numerical benefits on quality of life were seen with FSC
      250/50 compared with SAL. The incidence of adverse events was similar across
      groups. Pneumonia was reported more frequently with FSC 250/50 compared with SAL
      (7% vs. 2%). FSC 250/50 is more effective than SAL at reducing the rate of
      moderate/severe exacerbations. These data confirm the beneficial effect of FSC on
      the management of COPD exacerbations and support the use of FSC in patients with
      COPD.

PMID- 19863362
TI  - Paced-walk and step tests to assess exertional dyspnea in COPD.
AB  - This study reports on the development and test-retest reproducibility of a
      modified shuttle walking and step testing protocols to assess exertional dyspnea
      in patients with COPD. Patients with COPD randomly performed four externally
      paced 3-min bouts of shuttle walking at 1.5, 2.5, 4.0 and 6.0 km x h(- 1) or
      stepping at constant rate of 18, 22, 26 and 32 steps x min(- 1). Walking and
      stepping procedures were repeated once, on a separate occasion. Ventilation,
      heart rate, gas exchange parameters and dyspnea Borg scores were obtained at the
      end of each exercise bout. Most patients completed walking or stepping at the
      slow and middle speed cadences but only 33% completed walking at 6.0 km x h(- 1)
      and 40% completed stepping at 32 steps x min(- 1). Walking and stepping at
      progressively faster pace caused a progressive increase in ventilation and
      dyspnea. Test-retest Pearson correlation coefficients for ventilation, heart
      rate, gas exchange parameters and dyspnea scores over the four exercise bouts,
      all exceeded 0.80. Intra-class correlation coefficients were at least as strong
      as Pearson coefficients. Bland & Altman representation showed that for repeated
      Borg scores, 92 and 96% of points lied within 2 SD of the mean difference between
      test-retest values for walking and stepping. The majority of moderate and severe
      COPD patients completed the 3-min shuttle waking testing at 1.5 to 4.0 km x h(-
      1) and the 3-min of step testing at rates between 18 and 26 steps x min(- 1).
      Both field tests were highly reproducible in patients with COPD.

PMID- 19863363
TI  - Performance during constant workrate cycling exercise in women with COPD and
      hyperinflation.
AB  - We aimed to characterize gender differences in exercise endurance, operating lung
      volumes and symptoms limitation during exercise in patients with COPD. Ninety
      three women and 93 men with COPD matched for age and disease severity were
      evaluated during symptom-limited constant-work rate cycle exercise at 75% of peak
      capacity. Breathing pattern, inspiratory capacity, dyspnoea and leg discomfort
      Borg scores were recorded during exercise. Endurance time was shorter in women
      compared to men. Inspiratory capacity decreased at a similar rate during exercise
      in women and men (0.71 vs. 0.81 ml x s(- 1) for women and men respectively, p =
      0.47) despite lower ventilation at end-exercise in women. At end-exercise, women
      showed lower inspiratory reserve volume (p < 0.005). Dyspnoea responses during
      exercise occurred with a steep rise near end-exercise, when inspiratory reserve
      volume approached a critical value, at 10% of total lung capacity, this onset of
      dyspnoea acceleration occurred earlier in women (p < 0.0001). At the same
      relative exercise intensity, women with COPD had lower endurance time than men.
      Compared to men, women with COPD were disadvantaged during exercise as they
      reached a critical inspiratory reserve volume earlier, leading to a steep
      increase in dyspnoea and to exercise termination.

PMID- 19863364
TI  - A self-management education program including an action plan for acute COPD
      exacerbations.
AB  - Exacerbations are an important cause of morbidity and mortality in COPD. We
      assessed treatment initiation and health care use at exacerbation in patients
      receiving a self-management education program including an action plan. COPD
      patients were randomly assigned to usual care or to a comprehensive self
      management program "Living Well with COPD" including a written action plan and
      case manager support, and were followed-up for 12 months. Patients in the usual
      care were managed by their respective practitioners. Patients in the self
      management program received, as part of a written action plan, a prescription of
      antibiotics and prednisone for self-initiation in case of aggravation of 2 or
      more symptoms (dyspnea, sputum volume, sputum purulence) for at least 24 hours,
      and they had the support of a case-manager for reinforcement and monthly
      telephone follow-ups. At 12 months, 166 patients presented with at least one
      exacerbation. Exacerbations (606) were confirmed by aggravation of at least one
      symptom; 403 (67.6%) presented 2 or more. Antibiotics were used in 61.6% of
      exacerbations and prednisone in 47.9%. In exacerbations presenting aggravation of
      2 or more symptoms, antibiotics and prednisone were used together more often in
      the action plan than in the usual care group (54.4% vs. 34.8%, p < 0.001). In the
      action plan, compared to the usual care group, 17.2% vs. 36.3% exacerbations
      resulted in a hospitalization (p < 0.001). Self-management with the successful
      use of an action plan for acute exacerbation of COPD holds promise for reducing
      health care use.

PMID- 19863365
TI  - Family relationship quality is associated with psychological distress, dyspnea,
      and quality of life in COPD.
AB  - Family relationship quality predicts medical outcomes in various health
      conditions, including stroke, end stage renal disease, and heart failure. Family
      relationships also influence the onset and course of depression and anxiety
      disorders. Family may be particularly important in COPD given the high prevalence
      of depression and anxiety in COPD patients and the association of depression and
      anxiety with important clinical features of COPD such as dyspnea. The objective
      of this study was to test three hypotheses in a sample of individuals with COPD:
      (1) unsupportive family relationships are associated with psychological distress;
      (2) psychological distress is associated with dyspnea and impairment in health
      related quality of life; and (3) unsupportive family relationships are indirectly
      associated with dyspnea and health-related quality of life via psychological
      distress. Cross-sectional data were collected via self-report questionnaires
      completed by 526 individuals with COPD. Structural equation modeling was used to
      test the hypotheses. All three hypotheses were supported. Unsupportive family
      relationships were associated with psychological distress, psychological distress
      was associated with dyspnea and impairment in health-related quality of life, and
      unsupportive family relationships were indirectly associated with dyspnea and
      health-related quality of life via psychological distress. If subsequent
      longitudinal investigations demonstrate that unsupportive family relationships do
      indeed lead to psychological distress among individuals with COPD, then
      interventions to improve family relationships of patients with COPD could lead to
      reductions in psychological distress and, ultimately, to improvements in dyspnea
      and quality of life.

PMID- 19863366
TI  - Chronic obstructive pulmonary disease in UK primary care: incidence and risk
      factors.
AB  - We evaluated the association of chronic obstructive pulmonary disease (COPD) with
      modifiable risk factors such as smoking and prescription medications, and
      investigated possible risk factors unique to patients who had never smoked. The
      UK General Practice Research Database was used to identify a cohort of patients
      with a first diagnosis of COPD (n = 1927) along with age- and sex-matched
      controls without COPD (n = 16 546). The incidence of COPD diagnoses and the risks
      associated with medication use, co-morbidities, and demographic factors, were
      estimated. The incidence of COPD was 2.6 per 1000 person-years (95% confidence
      interval [CI]: 2.5-2.7) among 40-89 year-olds. The risk significantly increased
      in current and former smokers (OR: 6.15 [95% CI: 5.41-7.00] and 3.45 [95% CI:
      2.96-4.02]), respectively. The risk was significantly lower in former smokers
      than current smokers (OR: 0.61; 95% CI: 0.52-0.71). Current statin use was
      significantly associated with a reduced risk (OR: 0.45; 95% CI: 0.25-0.80). In
      never smokers, risk factors included advanced age and obesity. The risk in never
      smokers was more strongly related to paracetamol use (OR: 1.82; 95% CI: 1.33
      2.49) than in current and former smokers (OR: 1.48; 95% CI: 1.18-1.86). In
      summary, COPD is associated with a range of cardiovascular and respiratory
      conditions and the risk is influenced by current and past medications. While the
      risk factors are similar in smokers and never smokers, some were unique to never
      smokers. Moreover, subjects who stopped smoking had a substantially lower COPD
      risk than those who continued smoking.

PMID- 19863367
TI  - Prevalence of chronic obstructive pulmonary disease in the U.S. working
      population: an analysis of data from the 1997-2004 National Health Interview
      Survey.
AB  - To estimate the prevalence and the population attributable fraction of chronic
      obstructive pulmonary disease (COPD) in the U.S. adult workers, we analyzed data
      obtained from the National Health Interview Surveys for the period 1997-2004. The
      overall COPD prevalence was 4.0% (95% confidence interval [CI] 3.9-4.1%). The
      prevalence was higher in females (5.4%, 95% CI 5.3-5.6%) than in males (2.8%, 95%
      CI 2.7-2.9%); in Whites (4.2%, 95% CI 4.1-4.3%) than in Blacks (3.4%, 95% CI 3.1
      3.7%) and other races (2.4%, 95% CI 2.1-2.8%). Compared with insurance, real
      estate and other finance industry, the top three industries associated with
      significantly higher prevalence odds ratios (PORs) (adjusted for age, sex, race,
      and smoking) were other educational services (POR = 1.5, 95% CI 1.0-2.3);
      transportation equipment (POR = 1.4, 95% CI 1.1-1.8); and social services,
      religious and membership organizations (POR = 1.4, 95% CI 1.1-1.7). Compared with
      managers and administrators, except public administration occupation, the top
      three occupations with significantly higher PORs were health service (1.8, 95% CI
      1.5-2.1), other protective service (POR = 1.6, 95% CI 1.2-2.2), and material
      moving equipment operators (POR = 1.6, 95% CI 1.1-2.3). The overall population
      attributable fraction for association of COPD with employment was 12.2% for
      industry and 17.4% for occupation. Further studies are needed to determine
      specific risk factors associated with COPD in industries and occupations with
      elevated prevalence and POR.

PMID- 19863368
TI  - Identifying individuals with physcian diagnosed COPD in health administrative
      databases.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory
      disease responsible for significant morbidity and mortality. Population-based
      health administrative databases provide a powerful and unbiased way of studying
      COPD in the population, however, their ability to accurately identify patients
      with this disease must first be confirmed. The objective was to validate
      population-based health administrative definitions of COPD. Previously abstracted
      medical records of adults over the age of 35 randomly selected from primary care
      practices in Ontario, Canada were reviewed by an expert panel to establish if an
      individual did or did not have a diagnosis of COPD. These reference designations
      were then linked to each individual's respective health administrative database
      record and compared with predefine health administrative data definitions of
      COPD. Concepts of diagnostic test evaluation were used to calculate and compare
      their test characteristics. The most sensitive health administrative definition
      of COPD was 1 or more ambulatory claims and/or 1 or more hospitalizations for
      COPD that yielded a sensitivity of 85.0% (95% confidence interval 77.0 to 91.0)
      and a specificity of 78.4% (95% confidence interval 73.6 to 82.7). As number of
      ambulatory claims in the definition increased, sensitivity decreased and
      specificity increased. Individuals with COPD can be accurately identified in
      health administrative data, and therefore it may be used to create an unbiased
      population cohort for surveillance and research. This offers a powerful means of
      generating evidence to inform strategies that optimize the prevention and
      management of COPD.

PMID- 19863369
TI  - Is there a role for antiinflammatory treatment in COPD?
AB  - By definition, chronic obstructive pulmonary disease (COPD) is associated with an
      abnormal inflammatory response of affected lungs. Therefore, the search for an
      effective anti-inflammatory therapy for this debilitating disease is intense.
      However, to date, there is no such anti-inflammatory treatment for COPD. While
      there are some modest effects of inhaled corticosteroids on selected clinical
      endpoints in COPD, it remains to be proven that the observed effects are due to
      changes in the underlying inflammation, in particular since relevant clinical
      endpoints of COPD can be significantly improved by treatments not targeting
      inflammation. Therefore, it appears justified to reconsider the present knowledge
      about any linkage of local and systemic inflammation and clinical features of
      COPD, including lung function, exacerbations, disease progression, and mortality.
      Any such link needs to be carefully established before future anti-inflammatory
      therapies for COPD are developed and investigated in clinical trials, in
      particular since proof-of-concept trials aiming merely at inflammatory markers in
      COPD may not be predictive of clinical success or failure. The present review
      summarizes current knowledge about the role of inflammation in COPD, and
      critically analyzes results from clinical trials with inhaled corticosteroids and
      phosphodiesterase-4 inhibitors in COPD, the two classes of putative
      antiinflammatory agents with the richest body of evidence from controlled
      studies.

PMID- 19863370
TI  - Combination of formoterol and tiotropium in the treatment of COPD: effects on
      lung function.
AB  - Bronchodilators are central in symptomatic management of all stages of COPD. For
      patients whose COPD is not sufficiently controlled by monotherapy, combining an
      inhaled anticholinergic and a ss(2)-agonist is a convenient way of delivering
      treatment and obtaining better lung function and improved symptoms. Formoterol
      (beta(2)-agonist) and tiotropium (anticholinergic) are long-acting
      bronchodilators with different mechanisms of action. Formoterol has a fast onset
      and a bronchodilator effect of approximately 12 h, while tiotropium has a 24-h
      bronchodilator effect and is given once daily. Currently, there is no
      documentation that tiotropium is superior to formoterol or the contrary, but a
      combination of tiotropium and formoterol is more effective than single drugs
      alone in inducing bronchodilation and a bronchodilator-mediated symptom benefit
      in patients suffering from COPD. Once-daily or twice-daily formoterol, added to
      tiotropium, are both better than tiotropium alone, but the published evidence
      suggests twice-daily formoterol is the best add-on option.

PMID- 19863372
TI  - Renoprotection by alpha-Mangostin is related to the attenuation in renal
      oxidative/nitrosative stress induced by cisplatin nephrotoxicity.
AB  - Cisplatin (CDDP) is a chemotherapeutic agent that produces nephrotoxicity
      associated with oxidative/nitrosative stress. alpha-Mangostin (alpha-M) is a
      xanthone extracted from mangosteen with antioxidant and anti-inflammatory
      properties. The purpose of this study was to evaluate the renoprotective effect
      of alpha-M on the CDDP-induced nephrotoxicity. alpha-M was administered (12.5
      mg/kg/day, i.g.) for 10 days (7 days before and 3 days after CDDP injection). On
      day 7, rats were treated with a single injection of CDDP (7.5 mg/Kg, i.p.); 3
      days after the rats were killed. alpha-M attenuated renal dysfunction, structural
      damage, oxidative/nitrosative stress, decrease in catalase expression and
      increase in mRNA levels of tumour necrosis factor alpha and transforming growth
      factor beta. In conclusion the renoprotective effect of alpha-M on CDDP-induced
      nephrotoxicity was associated with the attenuation in oxidative/nitrosative
      stress and inflammatory and fibrotic markers and preservation of catalase
      activity.

PMID- 19863373
TI  - Ferulic acid inhibits oxidative stress and cell death induced by Ab oligomers:
      improved delivery by solid lipid nanoparticles.
AB  - Oxidative stress and dysfunctional mitochondria are among the earliest events in
      AD, triggering neurodegeneration. The use of natural antioxidants could be a
      neuroprotective strategy for blocking cell death. Here, the antioxidant action of
      ferulic acid (FA) on different paths leading to degeneration of recombinant beta
      amyloid peptide (rAbeta42) treated cells was investigated. Further, to improve
      its delivery, a novel drug delivery system (DDS) was used. Solid lipid
      nanoparticles (SLNs), empty or containing ferulic acid (FA-SNL), were developed
      as DDS. The resulting particles had small colloidal size and highly negative
      surface charge in water. Using neuroblastoma cells and rAbeta42 oligomers, it was
      demonstrated that free and SLNs-loaded FA recover cell viability. FA treatment,
      in particular if loaded into SLNs, decreased ROS generation, restored
      mitochondrial membrane potential (Deltapsi(m)) and reduced cytochrome c release
      and intrinsic pathway apoptosis activation. Further, FA modulated the expression
      of Peroxiredoxin, an anti-oxidative protein, and attenuated phosphorylation of
      ERK1/2 activated by Abeta oligomers.

PMID- 19863374
TI  - Endothelial damage and autoimmune diseases.
AB  - This issue of Autoimmunity reviews the mechanisms that lead to vascular damage in
      systemic autoimmune diseases. In addition, this issue explores recent advances in
      the understanding of how abnormalities in angiogenesis present in autoimmune
      diseases may lead to tissue damage and/or to premature vascular disease.

PMID- 19863376
TI  - The role of angiogenesis in the pathogenesis of psoriasis.
AB  - Psoriasis is a multifactorial skin disorder with known systemic consequences.
      While most recent studies point to a predominantly Th17-driven process, psoriasis
      also lies at the crossroads linking the pathways of angiogenesis and
      inflammation. Mediators such as VEGF and angiopoietin-2 play significant roles in
      the pathophysiology and may even account for the maintenance of the chronic
      inflammatory state. Targets in this shared pathway may offer alternative avenues
      for therapy.

PMID- 19863375
TI  - Angiogenesis in rheumatoid arthritis.
AB  - Angiogenesis is the formation of new capillaries from pre-existing vessels. A
      number of soluble and cell-bound factors may stimulate neovascularization. The
      perpetuation of angiogenesis involving numerous soluble and cell surface-bound
      mediators has been associated with rheumatoid arthritis (RA). These angiogenic
      mediators, among others, include growth factors, primarily vascular endothelial
      growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as pro
      inflammatory cytokines, various chemokines, matrix components, cell adhesion
      molecules, proteases and others. Among the several potential angiogenesis
      inhibitors, targeting of VEGF, HIF-1, angiogenic chemokines, tumor necrosis
      factor-alpha and the alpha(V)beta(3) integrin may attenuate the action of
      angiogenic mediators and thus synovial angiogenesis. In addition, some naturally
      produced or synthetic compounds including angiostatin, endostatin, paclitaxel,
      fumagillin analogues, 2-methoxyestradiol and thalidomide may be included in the
      management of RA.

PMID- 19863377
TI  - Mechanisms of vascular damage in systemic sclerosis.
AB  - Although being classified as autoimmune connective tissue disease, dominant
      components of the pathophysiology of systemic sclerosis (SSc) consists of
      mechanisms of vascular damage, which can occur early in the course of the
      disease. Amongst them are abnormal vasoreactivity, hypoxia, insufficient
      neoangiogenesis and direct damage of vascular and perivascular cells. They result
      in a decreased capillary blood flow, and subsequently in clinically overt
      symptoms such as Raynaud's syndrome and fingertip ulcers. In addition, in active
      disease vascular pathology can affect various other organs, predominantly the
      lung, the kidney, the heart but also the gastrointestinal tract. Vascular
      pathology contributes also significantly to overall morbidity and mortality in
      SSc patients and reduces life expectancy by at least a decade. Fortunately,
      molecular biology has revealed a number of underlying pathways on the cellular
      and subcellular levels, including key factors of the aberrant function of
      (peri)vascular cells and autoimmune effector cells, the dysregulation of
      vasoconstrictive molecules and their receptors, the upregulation of intracellular
      signaling kinases and the altered balance of hypoxia-induced vascular growth
      factors. This increasing knowledge of vascular pathology in SSc has also resulted
      in novel therapeutic approaches ranging from endothelin antagonists to
      application of progenitor cells to counteract this aberrant vascular pathology
      and to support the repair of the dysfunctional vasculature.

PMID- 19863378
TI  - Mechanisms and markers of vascular damage in ANCA-associated vasculitis.
AB  - Much progress has been made in understanding the pathogenesis of anti-neutrophil
      cytoplasmic antibodies (ANCA)-associated small-vessel vasculitis and interaction
      between ANCA and micro-vascular endothelial cells are centre stage. The
      interactions of these key players culminate in respiratory burst of the
      neutrophil with release of radicals and proteases and subsequent endothelial cell
      and tissue damage. During the last decade, markers have become available to
      assess the extent and/or acuity of vascular damage in a clinical setting. First,
      circulating endothelial cells (CEC) have emerged as reliable surrogate markers of
      endothelial damage in vasculitis. More recently, endothelial microparticles have
      been used and appear to reflect damage and activation of the cells. Data on
      endothelial progenitor cells in vasculitis are sparse but intriguing while a
      genuine progenitor cell deficiency remains controversial. The severely damaged
      phenotype of CEC in vasculitis led to the hypothesis that such circulating
      apoptotic and/or necrotic debris may itself be a mediator of disease and first
      data from experimental studies have added proof to this assumption. Such effects
      may well contribute to a pro-inflammatory environment in ANCA-associated small
      vessel vasculitis and in vascular disease in general. Here, we review mechanisms
      and markers of endothelial damage and repair in ANCA-associated vasculitis and
      put these findings into perspective.

PMID- 19863379
TI  - Vascular involvement in the pathogenesis of idiopathic inflammatory myopathies.
AB  - The identification of the exact role of the involvement of the vascular system in
      the pathogenesis of idiopathic inflammatory myopathies (IIMs) has been the task
      of several scientific investigations during the recent years. The observations
      that microcirculatory disturbances might play a major-if not perhaps the primary
      role in IIMs have gained wide recognition among the scientific community and led
      to different experimental and clinical attempts to study the role of microvessels
      in IIMs. During the past years, the 'Vascular Hypothesis' of the pathogenesis of
      IIMs has been co-developed in our laboratory supported by experimental and
      clinical data. This hypothesis is based on assumptions that phenotypically
      altered microvessels might affect the local circulation of the muscle and hence
      lead to the development of tissue hypoxia and metabolic alterations.
      Subsequently, local hypoxia in muscle tissue could lead to muscle weakness and
      muscle fatigue, which are the most prominent clinical signs in IIM patients. This
      hypothesis is further supported by the reported benefits of physical exercise and
      associated molecular alterations in muscle in patients with IIMs. This review
      will highlight some of the most important findings that elucidate the role of
      vascular endothelial cell dysfunction and hypoxia in the pathogenesis of IIMs.

PMID- 19863380
TI  - Immune-mediated mechanisms of endothelial damage in atherosclerosis.
AB  - The endothelium of the vessel wall as a barrier between blood and the
      subendothelial matrix proteins is essential for preventing thrombus formation and
      subsequent atherosclerosis development. Atherosclerosis is an inflammatory
      disease in which immune and autoimmune mechanisms are involved. Recently, it was
      demonstrated that endothelial cells in the vessel wall can be damaged not only by
      classic risk factors, such as hyperlipidemia, smoking and disturbed blood flow,
      but also (auto)immune reactions to autoantigens present in the cell surface,
      among which heat shock protein 60 (HSP60) was mostly studied. HSP60 normally
      located in mitochondria can be translocated into the cell member in response to
      stress stimuli. Meanwhile, autoantibodies against HSP60 are present in most
      subjects, especially patients with heart attack and stroke. These autoantibodies
      may bind to HSP60 expressed in endothelial cells resulting in the cell damage,
      subsequently initiating the formation of atherosclerotic lesions. Based on the
      recent progress in the research field, the present review will update the
      mechanisms of immune response to endothelial cells by which cell damage can
      initiate the development of atherosclerosis.

PMID- 19863381
TI  - Allelopathy in freshwater cyanobacteria.
AB  - Freshwater cyanobacteria produce several bioactive secondary metabolites with
      diverse chemical structure, which may achieve high concentrations in the aquatic
      medium when cyanobacterial blooms occur. Some of the compounds released by
      cyanobacteria have allelopathic properties, influencing the biological processes
      of other phytoplankton or aquatic plants. These kinds of interactions are more
      easily detectable under laboratory studies; however their ecological relevance is
      often debated. Recent research has discovered new allelopathic properties in some
      cyanobacteria species, new allelochemicals and elucidated some of the
      allelopathic mechanisms. Ecosystem-level approaches have shed some light on the
      factors that influence allelopathic interactions, as well as how cyanobacteria
      may be able to modulate their surrounding environment by means of allelochemical
      release. Nevertheless, the role of allelopathy in cyanobacteria ecology is still
      not well understood, and its clarification should benefit from carefully designed
      field studies, chemical characterization of allelochemicals and new
      methodological approaches at the "omics" level.

PMID- 19863382
TI  - Review: Microbiological quality and safety of fruit juices--past, present and
      future perspectives.
AB  - In this review paper, several aspects of fruit juice microbiology, from past to
      future perspectives, are considered. An overview of the most relevant outbreaks
      involving foodborne pathogens and spoilage microorganisms associated with fruit
      juices is provided. One of the sections provides data on the sources of fruit
      juice contamination, followed by perspectives on preservation methods.
      Furthermore, considerations on the role of international guidelines about exotic
      fruit juices in respect to public health, and of the microbiological status of
      fruit juices used as food/beverage ingredients are discussed. Issues and
      challenges highlight how the microbiology of fruit juices has evolved over the
      years, when aspects of stability or microbiological safety are under
      consideration.

PMID- 19863383
TI  - Our current understanding of fungal biofilms.
AB  - Fungal biofilms are an escalating clinical problem associated with significant
      rates of mortality. Candida albicans is the most notorious of all fungal biofilm
      formers. However, non-Candida species, yeasts such as Cryptococcus neoformans,
      and filamentous moulds such as Aspergillus fumigatus, have been shown to be
      implicated in biofilm-associated infections. Fungal biofilms have distinct
      developmental phases, including adhesion, colonisation, maturation and dispersal,
      which are governed by complex molecular events. Recalcitrance to antifungal
      therapy remains the greatest threat to patients with fungal biofilms. This review
      discusses our current understanding of the basic biology and clinical
      implications associated with fungal biofilms.

PMID- 19863384
TI  - Fungal spores: a critical review of the toxicological and epidemiological
      evidence as a basis for occupational exposure limit setting.
AB  - Fungal spores are ubiquitous in the environment. However, exposure levels in
      workplaces where mouldy materials are handled are much higher than in common
      indoor and outdoor environments. Spores of all tested species induced
      inflammation in experimental studies. The response to mycotoxin-producing and
      pathogenic species was much stronger. In animal studies, nonallergic responses
      dominated after a single dose. Allergic responses also occurred, especially to
      mycotoxin-producing and pathogenic species, and after repeated exposures.
      Inhalation of a single spore dose by subjects with sick building syndrome
      indicated no observed effect levels of 4 x 10(3) Trichoderma harzianum
      spores/m(3) and 8 x 10(3) Penicillium chrysogenum spores/m(3) for lung function,
      respiratory symptoms, and inflammatory cells in the blood. In asthmatic patients
      allergic to Penicillium sp. or Alternaria alternata, lowest observed effect
      levels (LOELs) for reduced airway conductance were 1 x 10(4) and 2 x 10(4)
      spores/m(3), respectively. In epidemiological studies of highly exposed working
      populations lung function decline, respiratory symptoms and airway inflammation
      began to appear at exposure levels of 10(5) spores/m(3). Thus, human challenge
      and epidemiological studies support fairly consistent LOELs of approximately
      10(5) spores/m(3) for diverse fungal species in nonsensitised populations.
      Mycotoxin-producing and pathogenic species have to be detected specifically,
      however, because of their higher toxicity.

PMID- 19863385
TI  - Health effects of concentrated ambient air particulate matter (CAPs) and its
      components.
AB  - We review literature that provides insights on health-related effects observed in
      laboratory-based inhalation studies in humans and laboratory animals using
      concentrated ambient air particulate matter (CAPs) in the fine, thoracic coarse,
      and ultrafine size ranges. The CAPs studies are highly informative on the health
      effects of ambient air particulate matter (PM) because they represent realistic
      PM exposure mixtures. When PM components are also analyzed and regressed against
      the effects, they can sometimes be used to identify influential individual
      components or source-related mixtures responsible for the effects. Such CAPs
      inhalation studies are analogous to epidemiological studies of human populations
      for which both health-related effects were observed and PM composition data were
      available for multi-pollutant regression analyses or source apportionment.
      Various acute and chronic health-related effects have occurred in short- and long
      term CAPs inhalation studies in the cardiovascular, nervous, hepatic, and
      pulmonary systems, as well as changes in markers of the metabolic syndrome, and
      many correspond to effects associated with ambient air PM exposures in
      epidemiological studies. In addition, many CAPs studies have been conducted in
      coordination with in vitro studies that have identified biomarkers indicative of
      the underlying biological mechanisms that account for the responses.

PMID- 19863386
TI  - Effects of passive stretching on the biochemical and biomechanical properties of
      calcaneal tendon of rats.
AB  - The role of physical activity in affecting the composition of extracellular
      matrix and mechanical properties of tendons has been well studied, but little is
      known about the role of passive stretching. The purpose of this study was to test
      the hypothesis that stimulation by passive stretching may change the composition
      and mechanical properties of tendons. Three-month-old Wistar rats were divided
      into three groups: the control, animals were not submitted to stretching
      procedures; groups that had their calcaneal tendons manually stretched three or
      five times a week, for 21 days. Afterward, the calcaneal tendons were removed and
      assayed for hydroxyproline content and biomechanical test. The hydroxyproline
      content in the stretched groups was higher, suggesting that more collagen was
      present in the tendons of these groups. These tendons also showed higher values
      of maximum stress and modulus of elasticity or Young's modulus. These results
      indicate that stretching leads to alterations in the synthesis of the
      extracellular matrix components and in the mechanical properties of tendons.

PMID- 19863387
TI  - In vitro regulation of CaCO(3) crystal growth by the highly acidic proteins of
      calcitic sclerites in soft coral, Sinularia Polydactyla.
AB  - Acidic proteins are generally thought to control mineral formation and growth in
      biocalcification. Analysis of proteinaceous components in the soluble and
      insoluble matrix fractions of sclerites in Sinularia polydactyla indicates that
      aspartic acid composes about 60% of the insoluble and 29% of the soluble matrix
      fractions. We previously analyzed aspartic acids in the matrix fractions
      (insoluble = 17 mol%; soluble = 38 mol%) of sclerites from a different type of
      soft coral, Lobophytum crassum, which showed comparatively lower aspartic acid
      rich proteins than S. polydactyla. Thus, characterization of highly acidic
      proteins in the organic matrix of present species is an important first step
      toward linking function to individual proteins in soft coral. Here, we show that
      aspartic-acid rich proteins can control the CaCO(3) polymorph in vitro. The
      CaCO(3) precipitates in vitro in the presence of aspartic acid-rich proteins and
      50 mM Mg(2+) was verified by Raman microprobe analysis. The matrix proteins of
      sclerites demonstrated that the aspartic-acid rich domain is crucial for the
      calcite precipitation in soft corals. The crystalline form of CaCO(3) in the
      presence of aspartic acid-rich proteins in vitro was identified by X-ray
      diffraction and, revealed calcitic polymorphisms with a strong (104) reflection.
      The structure of soft coral organic matrices containing aspartate-rich proteins
      and polysaccharides was assessed by Fourier transform infrared spectroscopy.
      These results strongly suggest that the aspartic acid-rich proteins within the
      organic matrix of soft corals play a key role in biomineralization regulation.

PMID- 19863388
TI  - Expression of laminin isoforms, receptors, and binding proteins unique to nucleus
      pulposus cells of immature intervertebral disc.
AB  - Intervertebral disc (IVD) disorders are believed to be related to aging-related
      cell loss and phenotypic changes, as well as biochemical and structural changes
      in the extracellular matrix of the nucleus pulposus (NP) region. Previously, we
      found that the laminin gamma1 chain was more highly expressed in immature NP
      porcine tissues, in parallel with the expression pattern for a laminin receptor,
      integrin alpha6 subunit, as compared to adjacent anulus fibrosus region. This
      result suggests that cell-matrix interactions may be unique to the immature NP.
      However, the identity of laminin isoforms specific to immature or mature NP
      tissues, their associated receptors, and functional significance are still poorly
      understood. In this study, we evaluated the zonal-specific expression of the
      laminin chains, receptors (i.e., integrins), and other binding proteins in
      immature tissue and isolated cells of rat, porcine and human intervertebral disc.
      Our goal was to reveal features of cellular environment and cell-matrix
      interactions in the immature NP. Results from both immunohistochemical staining
      and flow cytometry analysis found that NP cells expressed higher levels of the
      laminin alpha5 chain, laminin receptors (integrin alpha3, alpha6, beta4 subunit,
      and CD239), and related binding proteins (CD151), as compared to cells from
      adjacent anulus fibrosus. These differences suggest that laminin interactions
      with NP cells are distinct from that of the anulus fibrosus and that laminins may
      be important contributors to region-specific IVD biology. The revealed laminin
      isoforms, their receptors, and related binding proteins may be used as
      distinguishing features of these immature NP cells in the intervertebral disc.

PMID- 19863389
TI  - Histochemical analyses of tissue-engineered human menisci.
AB  - The field of tissue engineering remains one of the least explored areas of
      current meniscal research but holds great promise. In this investigation,
      meniscal fibrochondrocytes were isolated from fresh human meniscal tissue and
      seeded onto synthetic polyglycolic acid (PGA) scaffolds. Constructs were
      implanted into the dorsal subcutaneous space of athymic nude mice. Control
      scaffolds, devoid of meniscal cells, were simultaneously implanted in additional
      mice. Constructs were harvested over 12 weeks and treated with a variety of
      histochemical stains to analyze general specimen morphology, cellular viability
      and proliferation, and collagen secretion. Results indicate that meniscal
      fibrochondrocyte proliferation increased over the time of implantation with
      cellular consolidation occurring as the PGA scaffolding was progressively
      hydrolyzed. Collagen production also increased over time. There were favorable
      similarities between constructs and human meniscal controls in terms of cellular
      morphology, phenotypic expression, and collagen production. These initial
      findings demonstrate procedures supporting proliferation of meniscal
      fibrochondrocytes, expression of fibrochondral phenotype, and the formation of
      putative meniscal tissue.

PMID- 19863390
TI  - Coordinated expression of MMPs and TIMPs in rat knee intra-articular tissues
      after ACL injury.
AB  - Anterior cruciate ligament (ACL) has poor healing ability and an injured ACL
      would induce the degeneration of other intra-articular connective tissues.
      However, the coordinated expression and activities of matrix metalloproteinase
      (MMPs) in intra-articular tissues induced by ACL rupture were poorly understood.
      With a rat ACL rotating injury model, we found that after ACL injury, the mRNA
      levels of MMP-13, TIMP-1, and CD147 were significantly elevated in ACL, posterior
      cruciate ligament (PCL), synovium, meniscus, and cartilage. Also, MMP-2 activity
      was also elevated significantly in a time-dependent manner in all intra-articular
      tissues. Synovium showed the most capability to release MMPs, whereas ACL showed
      the highest MMP-13/TIMP-1 ratio. Generic MMP activity assay and zymography showed
      time dependent elevation of MMP activities in synovial fluids (SF). We concluded
      that the ACL injury would induce a coordinated response of intra-articular
      tissues to express MMPs, TIMPs, and CD147. The MMP activities in the
      microenvironment in SF would accumulate, released by all the intra-articular
      tissues, which would contribute to the knee damage and degeneration induced by
      ACL injury.

PMID- 19863391
TI  - Cyclical cell stretching of skin-derived fibroblasts downregulates connective
      tissue growth factor (CTGF) production.
AB  - Delayed healing of skin wounds can be caused by wound instability, whereas
      appropriate massage or exercise prevents sclerosis and scar contracture. However,
      the mechanism by which wound healing is related to mechanical stress has not been
      fully elucidated. The present study aimed to identify whether mechanical
      stretching of fibroblasts reduces their production of extracellular matrix. We
      transferred skin fibroblasts into collagen-coated elastic silicone chambers,
      cultured them on a stretching apparatus, and used RT-PCR to examine the effects
      of mechanical stretching on the expression levels of 17 genes related to
      extracellular matrix production and growth factor secretion. We found that
      connective tissue growth factor (CTGF) was downregulated after 24 hr of cell
      stretching. Specifically, the CTGF mRNA and protein levels were 50% and 48% of
      the control levels, respectively. These findings suggest that cyclic stretching
      of fibroblasts contributes to anti-fibrotic processes by reducing CTGF
      production.

PMID- 19863392
TI  - Date seed oil inhibits hydrogen peroxide-induced oxidative stress in normal human
      epidermal melanocytes.
AB  - The administration of antioxidants has been shown to enhance repair and healing
      processes in cutaneous tissue. Date seed oil (DSO) extract, which might be a
      potential source of natural antioxidants such as phenols and tocopherols, has
      been reported to be beneficial in the reduction of chemically induced oxidative
      stress in normal human skin. In this study, we investigated the protective
      effects of DSO against hydrogen peroxide (H(2)O(2))-induced oxidative stress in
      terms of lipid peroxidation, depletion of such endogenous antioxidant defense
      enzymes as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GPx) using normal human epidermal melanocytes (NHEM). The results showed that
      DSO, endowed with a radical scavenging ability, decreased oxidative injury by
      inhibition of damage caused by H(2)O(2). Treatment of NHEM with DSO inhibited
      H(2)O(2)-induced lipid peroxidation. In addition, the extract inhibited H(2)O(2)
      induced depletion of antioxidant defense components, such as SOD, CAT, and GPx.
      Our findings demonstrate that DSO is an efficient extract able to prevent
      melanocytes oxidative damage induced by H(2)O(2) exposure. Thus it may be a
      potential promising candidate, as a chemopreventive agent, in the development of
      melanocyte-related pathologies like vitiligo and melanoma.

PMID- 19863393
TI  - Osteoblastic behavior of human bone marrow cells cultured over adsorbed collagen
      layer, over surface of collagen gels, and inside collagen gels.
AB  - While collagen type I is often used as a substrate for cell culturing and as a
      coating in biomedical implants, as far as we know a simple systematic study
      comparing the effects of the different presentations of collagen type I on the
      osteoblastic behavior of cells is missing. In this work, human bone marrow cells
      (hBMCs) were cultured under osteoblastic-inducing conditions, for 21 days, over a
      layer of adsorbed collagen (monomeric) and on the surface and inside collagen
      gels (fibrillar). Comparison was made based on three classical parameters; cell
      proliferation/viability, alkaline phosphatase (ALP) activity, and production of
      mineral deposits. The three types of collagen type I substrates allowed the
      adhesion, proliferation, and the osteoblastic differentiation of cells. However,
      hBMCs behavior was influenced by the monomeric/fibrillar and 2-/3-dimensional
      nature of the collagen substrates, namely: monomeric collagen favored cell
      attachment; cells on 2D substrates presented higher proliferation rates during
      the exponential phase of growth with formation of spiral-like multilayered
      structures; cells seeded inside 3D collagen gels formed a regular dense cellular
      mesh and had a low proliferating rate; cells cultured over or inside fibrillar
      collagen differentiated faster, with the 3D cultures presenting higher levels of
      ALP activity; and the extension of mineralization was greater for the cultures
      done over or inside fibrillar collagen. Thus, cells cultured over collagen gels
      showed both the ability for cell proliferation and for earlier differentiation, a
      fact that can be exploited in the biomaterials field.

PMID- 19863396
TI  - Editorial.

PMID- 19863395
TI  - Microembolic signals and carotid plaque characteristics in patients with
      asymptomatic carotid stenosis.
AB  - OBJECTIVE: To investigate the association between carotid plaque characteristics
      and the occurrence of cerebral microemboli signals (MES) and subsequent ischemic
      events in patients with asymptomatic carotid stenosis (ACS). DESIGN: Sixty-two
      asymptomatic patients with 50-99% carotid stenosis underwent transcranial Doppler
      (TCD) monitoring to determine the relationship between MES and plaque
      characteristics. The patients were followed for 1 year, and the incidence of
      transient ischemic attack (TIA)/stroke was studied. RESULTS: MES were found in
      10/62 of the patients at baseline, and there was a significant difference between
      the patients with moderate stenosis and those with severe stenosis on the
      presence of MES (p = 0.016). Furthermore, MES were more frequently found in
      patients with irregular and/or heterogeneous plaques than in those with regular
      (p = 0.028) and/or homogeneous plaques (p = 0.021). The incidence of TIA/stroke
      occurred more frequently in patients with MES than those without MES (p = 0.009).
      The proportion of progressive carotid stenosis was 4/50 in the patients with 50
      99% stenosis during 1 year follow-up. CONCLUSION: Asymptomatic patients (with 50
      99% carotid stenosis) with MES presented a significantly increased frequency of
      severe stenosis, with irregular and heterogeneous plaques.

PMID- 19863398
TI  - Proceedings of the 154th Meeting of the Society of British Neurological Surgeons:
      Dublin, Ireland, October 2009 This meeting is being held at Croke Park Stadium,
      Dublin, on 28-30 October 2009 and is hosted by the Department of Neurosurgery,
      Beaumont Hospital, Dublin. These abstracts are published in advance of the
      meeting in the order of presentation. If any papers are subsequently not read to
      the Society or are withdrawn an addendum to this effect will be published in the
      next issue of the Journal.

PMID- 19863397
TI  - Mr. Anthony (tony) hockley.

PMID- 19863399
TI  - Proceedings of the 154th meeting of the society of british neurological surgeons:
      dublin, ireland, october 2009.

PMID- 19863400
TI  - Head injury rehabilitation: the role of a neurotrauma clinic.
AB  - Survivors of head injury are often left with varying degrees of disability and
      complex and varied needs, necessitating prolonged periods of rehabilitation and
      continuing care. Advances have been made in the acute management of these
      patients, but continuing management in terms of rehabilitation remains deficient
      with lack of specialist resources and a fragmented service. For head-injured
      patients, lack of access to appropriate ongoing rehabilitation may have profound
      effects on outcome and social re-integration. There are also considerable
      economic implications for planning and provision of services. The aims of this
      paper are to describe, review and evaluate the role of a Neurotrauma clinic
      within the Head Injury Service at Addenbrooke's Hospital, Cambridge. The
      multidisciplinary Neurotrauma clinic commenced in June 2003 following an
      extensive collaborative research programme to assess current regional head injury
      service provision and address deficiencies and management issues. Patients of all
      ages with ongoing problems following varying severity of head injury are followed
      up at 2 months + post-injury for as long as appropriate. Patients complete an SF
      36 and GOSE questionnaire at each clinic appointment and this self-reported data
      is complemented by neuropsychological assessments, and demographic data entered
      on a database. The clinic acts as a 'gateway' to access appropriate ongoing
      rehabilitation and a source of information and support. The routine collection of
      outcome data enables tracking of individual patient progress and outcome and
      provides an information resource for further research. The findings highlight
      deficiencies in rehabilitation both in general service provision and specific
      patient need. Evidence in support of demand, need and effectiveness of
      rehabilitation for head injury is particularly relevant within the limited
      resources of the NHS. Early indications show that a specialist clinic can assist
      in providing continuity of patient care, in improving coordination of services,
      and act as a resource for further research on epidemiology, outcome and impact of
      rehabilitation.

PMID- 19863401
TI  - A survey of post-craniotomy analgesia in British neurosurgical centres: time for
      perceptions and prescribing to change?
AB  - Patients undergoing craniotomy may experience moderate to severe pain
      postoperatively. An audit of analgesia of post-craniotomy patients at King's
      College Hospital demonstrated variable analgesic prescribing practices and
      suboptimal analgesia in some patients. Prior to introducing a formal post
      operative analgesic regime, a survey of the adult neurosurgical units within the
      United Kingdom was undertaken to ascertain whether there was a general consensus
      regarding post-craniotomy pain management. Questions were asked as to whether
      there was a standardized analgesic regime/protocol; which first, second, third,
      and fourth-line analgesics were used; whether non-steroidal anti-inflammatory
      drugs were used; what the preferred anti-emetic was; and whether pain was
      routinely assessed. We also undertook a survey of neurosurgeons,
      neuroanaesthetists, intensivists, and neurosurgery high dependency nurses within
      our institution to ascertain what their perceptions were of post-craniotomy pain.
      All 31 adult neurosurgical units were surveyed. Twenty three percent (7 units)
      had a standardized analgesic regime/protocol and 65% routinely assessed pain post
      operatively (20 units). Seventy percent of units used codeine phosphate or
      dihydrocodeine (22 units) as the first line opioid the other 30% using morphine
      (9 units). Forty two percent (13 units) used tramadol; patient controlled
      analgesia was used in 3 units. Regular paracetamol was prescribed in all but five
      (16%) units. Fifty two percent of units (16) used NSAIDs; of those that used
      NSAIDs 19% (3/16) prescribed them regularly. One unit used clonidine infusions.
      Anti-emetics were prescribed as required in all but two units. Cyclizine was the
      first-line anti-emetic in 45% of the units, ondansetron in 29% and metoclopramide
      in 16%. There is currently no consensus on pain management after craniotomy in
      neurosurgical centres in the UK. Until there are sufficiently powered randomized
      controlled studies to address the main safety and efficacy issues progress in
      this area will remain slow.

PMID- 19863402
TI  - Venoplasty and stenting of a jugular foramen meningioma.
AB  - The authors describe a novel approach to relieving major venous sinus stenosis at
      the level of the jugular bulb caused by a petrous meningioma. A balloon
      expandable renovascular stent was deployed via a jugular approach to restore
      venous outflow and thus reduce visual and vestibulocochlear symptoms.
      Endovascular balloon venoplasty and stenting may assess and restore cranial
      outflow in veins compressed by soft tumours in anatomical locations challenging
      to surgical resection, even in the absence of intracranial hypertension.

PMID- 19863403
TI  - Nephrogenic systemic fibrosis and contrast medium-induced nephropathy: a choice
      between the devil and the deep blue sea for patients with reduced renal function?

PMID- 19863404
TI  - Sonographic changes after removing all benign breast masses with sonographically
      guided vacuum-assisted biopsy.
AB  - BACKGROUND: Total removal of benign breast masses by vacuum-assisted biopsy (VAB)
      is now increasingly accepted as a treatment option. However, little is known
      about whether this procedure produces early changes on follow-up sonography and,
      if so, how often and what factors might influence them. PURPOSE: To evaluate
      sonographic changes after total removal of benign breast masses using
      sonographically guided VAB and to determine the influencing factors. MATERIAL AND
      METHODS: We evaluated sonographic changes prospectively 1 week, 1 month, and 6
      months after biopsying 32 benign masses from which all sonographic evidence had
      been removed during sonographically guided directional VAB performed with 8- or
      11-gauge needles. Procedural factors were documented and compared with
      sonographic findings. RESULTS: At 1-week follow-up, hematomas were observed in
      84% (27/32) of the lesions. After 1 month, while the hematomas had resolved in
      all but five lesions, focal new architectural distortion had developed in 26
      (90%) lesions; 11 lesions were graded as severe, mimicking malignancy. After 6
      months, 23 lesions with various degrees of architectural distortion were
      observed. Six of the 32 lesions (19%) contained a residual lesion. No
      statistically significant association between sonographic findings and procedural
      variables was identified, except between the degree of hematoma and lesion size.
      CONCLUSION: The total removal of benign breast masses using sonographically
      guided VAB frequently produces changes on follow-up sonography after 6 months.
      Although these changes failed to show statistical significance with procedural
      factors, a larger dedicated study is needed.

PMID- 19863405
TI  - Physiological fluctuation of (99m)Tc-sestamibi uptake in normal mammary glands: a
      systematic investigation in female rats.
AB  - BACKGROUND: Scintimammography is an imaging tool for the diagnosis and management
      of primary breast tumors. There remains a significant knowledge gap regarding the
      physiological fluctuations in the basal level of (99m)Tc-sestamibi uptake in
      normal mammary tissues with respect to the female reproductive cycle. PURPOSE: To
      systematically characterize (99m)Tc-sestamibi uptake in normal mammary tissues in
      female Sprague Dawley (SD) rats in different estrous phases. MATERIAL AND
      METHODS: The exact phase of the reproductive cycle was determined in 18 female SD
      rats. Each rat was sacrificed at 20 min after (99m)Tc-sestamibi injection (14.8
      MBq/kg). The mammary glands were dissected, and the radioactivity uptake was
      measured by gamma counting. RESULTS: Tc-99m-sestamibi uptake oscillates by about
      twofold and reaches a maximum at the proestrous phase of the rat reproductive
      cycle. CONCLUSION: Tc-99m-sestamibi uptake fluctuates significantly in normal
      mammary tissues in synchrony with the female reproductive cycle, and peaks in the
      proestrous phase in rats, which is equivalent to the early to mid-follicular
      phase in the human menstrual cycle. This finding will likely benefit the
      detection of breast lesions that may otherwise be obscured by fluctuating
      background signals in surrounding normal breast tissues.

PMID- 19863406
TI  - Multiple (18)F-FDG, PET-CT for postoperative monitoring of breast cancer
      patients.
AB  - BACKGROUND: Positron emission tomography (PET)-computed tomography (CT) may be
      useful in the post-treatment follow-up of breast cancer patients. PURPOSE: To
      assess the usefulness of (18)F-fluorodeoxyglucose (FDG) PET-CT (PET-CT) for
      postoperative monitoring of breast cancer patients. MATERIAL AND METHODS: One
      hundred twenty-nine PET-CT studies performed on 55 female postoperative breast
      cancer patients (median age 56 years, range 36-86 years) were analyzed. The
      median interval between the PET-CT studies was 6 months (range 1-15 months). In
      order to determine the usefulness of serial PET-CT examinations in the
      postoperative follow-up of breast cancer patients, the PET-CT findings were
      compared with the physical findings, findings obtained by other imaging
      modalities, and the (18)F-FDG-PET (PET) findings. RESULTS: The PET findings were
      negative in 4 metastatic bone lesions with a positive bone scan. The PET findings
      were also negative in 6 of 9 osteogenic bone metastases and one of 64 osteolytic
      bone lesions. There were 5 cases with false-positive of PET, which were
      determined to be areas of soft-tissue hyperactivity. All false-positive/-negative
      findings were corrected by the addition of CT. CONCLUSION: The results of this
      study lend support to the clinical role of PET-CT in the postoperative follow
      up/monitoring of breast cancer patients.

PMID- 19863407
TI  - Breast magnetic resonance imaging findings in women treated with toremifene for
      premenstrual mastalgia.
AB  - BACKGROUND: Toremifene, a selective estrogen receptor modulator, has been shown
      to be effective in alleviating premenstrual breast pain. However, the exact
      mechanism by which toremifene and related compounds work in premenstrual
      mastalgia is poorly understood. PURPOSE: To find out if the effect of toremifene
      on breast would be detectable with dynamic magnetic resonance imaging (MRI).
      MATERIAL AND METHODS: This randomized, double-blind crossover study was performed
      on women suffering from marked premenstrual mastalgia. Ten women were randomized
      to receive either toremifene (20 mg) or placebo from cycle day 15 until next
      menstruation for three menstrual cycles. After a washout period, the treatment
      was crossed over for three additional cycles. The MRI evaluations were performed
      premenstrually at the end of each treatment phase. Breast pain and quality-of
      life scores were collected from one baseline cycle and from all the treatment
      cycles. RESULTS: Nine patients were evaluable for this analysis. Both the
      enhancement ratio and the maximum slope of enhancement tended to be smaller
      during the toremifene cycles as compared to placebo. On the left side, the
      difference in the maximum slope of enhancement between toremifene and placebo was
      statistically significant (median 5.150 [range 3.7-6.7] and 6.500 [range 4.9
      9.5], respectively; P=0.047). T2 relaxation times as well as breast pain and
      quality-of-life scores were inconsistent. CONCLUSION: Use of toremifene is
      associated with measurable changes in dynamic breast MRI findings in women with
      cyclic breast pain.

PMID- 19863408
TI  - Magnetic resonance imaging of breast cancer and correlation with prognostic
      factors.
AB  - BACKGROUND: Prognostic factors of breast cancer have been used for the prediction
      of clinical outcome or selection of patients for complementary treatment. Some of
      the imaging features of breast cancer, e.g. magnetic resonance imaging (MRI), are
      associated with these prognostic factors. PURPOSE: To evaluate the relationship
      between dynamic enhanced MR features and prognostic factors of clinical outcome
      of breast cancer. MATERIAL AND METHODS: A total of 136 patients with 151 breast
      cancers underwent 1.5T dynamic MR imaging with the use of a dynamic T1-weighted
      three-dimensional fast low-angle shot (FLASH) subtraction imaging technique.
      Morphological and kinetic analyses of MR features were evaluated using the
      American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI
      RADS) MRI lexicon. Pathological prognostic factors were correlated with MR
      imaging characteristics, including tumor size, histological grade, lymph node
      status, expression of estrogen receptor (ER), expression of progesterone receptor
      (PR), expression of c-erbB2, determination of Ki-67 index, and microvascular
      density (MVD), using univariate and multivariate statistical analyses. RESULTS:
      Based on univariate and multivariate analyses, spiculated tumor margins
      correlated significantly with lower histological grade (I-II) and positive PR
      expression. Rim enhancement was significantly correlated with high histological
      grade, presence of axillary lymph node metastasis, large tumor size, increased Ki
      67 index, and increased MVD. Early peak enhancement, as seen on the first scan
      after contrast medium injection, was correlated with negative ER expression.
      CONCLUSION: The presence of a lesion with a spiculated margin may predict a
      relatively good prognosis, and the presence of a lesion with rim enhancement may
      predict a relatively poor prognosis.

PMID- 19863409
TI  - Computer-aided detection in digital mammography: false-positive marks and their
      reproducibility in negative mammograms.
AB  - BACKGROUND: There are relatively few studies reporting the frequency of false
      positive computer-aided detection (CAD) marks and their reproducibility in normal
      cases. PURPOSE: To evaluate retrospectively the false-positive mark rate of a CAD
      system and the reproducibility of false-positive marks in two sets of negative
      digital mammograms. MATERIAL AND METHODS: Two sets of negative digital mammograms
      were obtained in 360 women (mean age 57 years, range 30-76 years) with an
      approximate interval of 1 year (mean time 343.7 days), and a CAD system was
      applied. False-positive CAD marks and the reproducibility were determined.
      RESULTS: Of the 360 patients, 252 (70.0%) and 240 (66.7%) patients had 1-7 CAD
      marks on the initial and second mammograms, respectively. The false-positive CAD
      mark rate was 1.5 (1.1 for masses and 0.4 for calcifications) and 1.4 (1.0 for
      masses and 0.4 for calcifications) per examination in the initial and second
      mammograms, respectively. The reproducibility of the false-positive CAD marks was
      12.0% for both mass (81/680) and microcalcification (33/278) marks. CONCLUSION:
      False-positive CAD marks were seen in approximately 70% of normal cases. However,
      the reproducibility was very low. Radiologists must be familiar with the findings
      of false-positive CAD marks, since they are very common and can increase the
      recall rate in screening.

PMID- 19863410
TI  - Diagnostic value of early-phase-enhanced computed tomography for the
      differentiation of pulmonary metastases from hepatocellular carcinoma and primary
      lung cancer.
AB  - BACKGROUND: The lung is the most common site of distant metastases from
      hepatocellular carcinoma. Correct differentiation between metastatic
      hepatocellular carcinoma of the lung and primary lung cancer is sometimes
      difficult without biopsy. PURPOSE: To evaluate the usefulness of measuring the
      attenuations of pulmonary nodules on early-phase contrast-enhanced computed
      tomography (CT) for the differentiation of pulmonary metastases from
      hepatocellular carcinoma and primary lung cancer. MATERIAL AND METHODS: Thirteen
      patients with pulmonary metastases from hepatocellular carcinoma (nine men, four
      women; age 53.9+/-14.2 years, range 16-70 years) and 25 patients with primary
      lung cancer (14 men, 11 women; age 62.2+/-9.4 years, range 43-72 years) were
      retrospectively evaluated. Contrast-enhanced scans were obtained 35 s after
      commencing intravenous injection of contrast medium. Attenuation values and the
      size of the pulmonary nodules were measured on contrast-enhanced CT scans. CT and
      clinical features were analyzed with regard to age, sex, body surface area of the
      patients, the attenuation values and size of the nodules, and CT machines using
      univariate analysis (Fisher's exact test for binary data sets and the Mann
      Whitney U test for continuous data sets). Multiple linear regression analysis was
      used to eliminate confounding factors. RESULTS: The mean attenuation value of
      metastatic pulmonary nodules from hepatocellular carcinoma (75.7+/-24.9 HU) was
      higher than that of primary lung cancer nodules (45.8+/-14.4 HU) (P<0.01). Other
      variables such as age, sex, body surface area of the patients, CT device, and
      nodule size were not significant variables on multiple regression analysis. When
      a cut-off value of 75 HU was applied, the positive predictive value for
      diagnosing metastatic nodules from hepatocellular carcinoma was 100%. CONCLUSION:
      Pending confirmation in a large study, our findings suggest that there is a
      difference in contrast enhancement between pulmonary metastases from
      hepatocellular carcinoma and primary lung cancer.

PMID- 19863411
TI  - Radiologic and clinical outcomes with special reference to tumor involvement
      pattern after stent placement for malignant bronchial obstructions.
AB  - BACKGROUND: Location of tumor within the tracheobronchial tree as well as its
      severity can affect the clinical outcome of patients who undergo airway stent
      placement. PURPOSE: To evaluate radiologic and clinical outcome, including
      survival data, with special reference to proposed tumor involvement pattern, in
      patients with malignant bronchial strictures. MATERIAL AND METHODS: A total of 35
      patients who underwent stent placement for malignant bronchial strictures were
      enrolled over a 9-year period. Tumor involvement pattern was divided into three
      types based on computed tomography (CT) scans and selective bronchography. Type I
      was defined as tumor involving only the main stem bronchus; type II, tumor
      involving the bronchus intermedius and/or the lower lobar bronchus without
      involvement of the lower-lobe segmental bronchus; and type III, tumor involving
      the lower lobar bronchus with involvement of the lower-lobe segmental bronchus.
      Tumor stage, lung collapse/infiltration, radiologic improvement, clinical
      improvement, and survival were compared according to the tumor involvement
      pattern. RESULTS: Tumor involvement pattern was of type I, II, and III in 14, 13,
      and eight patients, respectively. When comparisons were made between types I/II
      and type III to evaluate the influence of lower-lobe segmental bronchial
      involvement, radiologic and clinical improvement was significantly lower in type
      III than in types I/II, while advanced stage, lung collapse/infiltration, and
      median overall survival were not significantly different between types I/II and
      type III. CONCLUSION: In patients with malignant bronchial obstructions involving
      the lower-lobe segmental bronchus, clinicians must be aware of the possibility of
      less radiologic and clinical improvement following stent placement.

PMID- 19863412
TI  - Progression of emphysema evaluated by MRI using hyperpolarized (3)He (HP (3)He)
      measurements in patients with alpha-1-antitrypsin (A1AT) deficiency compared with
      CT and lung function tests.
AB  - BACKGROUND: The progression of emphysema is traditionally measured by pulmonary
      function test, with forced expiratory volume in 1 s (FEV(1)) being the most
      accepted and used measurement. However, FEV(1) is insensitive in detecting
      mild/slow progression of emphysema because of low reproducibility as compared to
      yearly decline. PURPOSE: To investigate the progression of emphysema over a
      period of 2 years using diffusion-weighted hyperpolarized (HP) (3)He magnetic
      resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency.
      MATERIAL AND METHODS: Nine patients with severe A1AT deficiency were studied over
      a period of 2 years (baseline, year 1, and year 2) with HP (3)He MRI using
      apparent diffusion coefficient (ADC), lung function tests (FEV(1) and carbon
      monoxide lung diffusion capacity [D(L,CO)]), and computed tomography (CT) using
      densitometric parameters (15th percentile density [CT-PD15] and relative area of
      emphysema below -910 HU [CT-RA-910]). RESULTS: Seven patients were scanned three
      times, one patient two times, and one patient only at baseline. The mean increase
      in ADC values from first to last HP (3)He MR scanning was 3.8% (0.014 cm(2)/s [SD
      0.024 cm(2)/s]; not significant). The time trends for FEV(1), D(L,CO), CT-PD15,
      and CT-RA-910 were all statistically significant. We found a high correlation
      between ADC and D(L,CO) (P<0.001). CONCLUSION: This pilot study indicates the
      possible use of nonionizing HP (3)He MRI for monitoring the progression of
      emphysema. However, in the future, larger studies are needed to confirm these
      preliminary results.

PMID- 19863414
TI  - Efficient use of automatic exposure control systems in computed tomography
      requires correct patient positioning.
AB  - BACKGROUND: Image quality and radiation dose to the patient are important factors
      in computed tomography (CT). To provide constant image quality, tube current
      modulation (TCM) performed by automatic exposure control (AEC) adjusts the tube
      current to the patient's size and shape. PURPOSE: To evaluate the effects of
      patient centering on tube current-time product (mAs) and image noise. MATERIAL
      AND METHODS: An oval-shaped acrylic phantom was scanned in various off-center
      positions, at 30-mm intervals within a 500-mm field of view, using three
      different CT scanners. Acquisition parameters were similar to routine abdomen
      examinations at each site. The mAs was recorded and noise measured in the images.
      The correlation of mAs and noise with position was calculated using Pearson
      correlation. RESULTS: In all three scanners, the mAs delivered by the AEC changed
      with y-position of the phantom (P<0.001), with correlation values of 0.98 for
      scanners A and B and -0.98 for scanner C. With x-position, mAs changes were 4.9%
      or less. As the phantom moved into the y-positions, compared with the iso-center,
      the mAs varied by up to +70%, -34%, and +56% in scanners A, B, and C,
      respectively. For scanners A and B, noise in two regions of interest in the lower
      part of the phantom decreased with elevation, with correlation factors from -0.95
      to -0.86 (P<0.02). In the x-direction, significant noise relationships (P<0.005)
      were only seen in scanner A. CONCLUSION: This study demonstrates that patient
      centering markedly affects the efficacy of AEC function and that tube current
      changes vary between scanners. Tube position when acquiring the scout projection
      radiograph is decisive for the direction of the mAs change. Off-center patient
      positions cause errors in tube current modulation that can outweigh the dose
      reduction gained by AEC use, and image quality is affected.

PMID- 19863413
TI  - Artifact reduction of susceptibility-weighted imaging using a short-echo phase
      mask.
AB  - BACKGROUND: Susceptibility-weighted imaging (SWI) is utilized in magnetic
      resonance (MR) venography and other applications, but can include artifacts
      caused by the phase-masking process. PURPOSE: To demonstrate risks of filter
      processes used in making phase masks for SWI, and to propose a simple method for
      reducing artifacts. MATERIAL AND METHODS: Phase linearity related to echo time
      (TE) was evaluated for the original phase and high-pass-filtered phase using a
      CuSO(4)-doped water phantom. Effect of filter size of the Hanning window and
      background homogeneity were also evaluated in a phantom study. Use of a phase
      mask generated by data with differing magnitudes of TE was attempted in a human
      study. Shorter TE was used for making the phase mask, and the number of
      multiplications was increased. As short and long TEs were necessary
      simultaneously for phase mask and T2* contrast, a dual-echo technique was used.
      RESULTS: Linearity of TE and phase value collapsed, and an unexpected negative
      phase appeared in the high-pass-filtered phase. Using a short-TE phase mask,
      phase-aliasing artifacts were reduced and visibility of deep veins was equivalent
      to that under conventional methods with an increased number of multiplications.
      CONCLUSION: Use of a short-echo phase mask in SWI is useful for reducing
      artifacts.

PMID- 19863415
TI  - Pitfalls in interpreting rat knee joint magnetic resonance images and their
      histological correlation.
AB  - BACKGROUND: Magnetic resonance (MR) imaging has been increasingly used as an
      investigational tool for assessing the structure and function of animal joint
      disease models, while to date MR tomographic knowledge of laboratory animal
      skeletal microanatomy remains limited. PURPOSE: To describe pitfalls in
      interpreting rat knee joint MR images and their histological correlation.
      MATERIAL AND METHODS: MR scans of the right knee of five 3-month-old Sprague
      Dawley (SD) rats were carried out using a 4.7T magnet, using a fat-suppressed
      three-dimensional (3D) gradient echo sequence with a spatial resolution of 59 x
      117 x 234 microm. Histology assessment with hematoxylin and eosin staining and
      Safranin O staining was carried out in the five 3-month-old SD rats and two SD
      rats of 1 month and 6 months old, respectively. MR images were analyzed by a
      radiologist, and histology data were assessed by a radiologist and a pathologist.
      RESULTS: Though the MR images were acquired in normal rats, many signs unfamiliar
      to radiologists were noted, including notch-like bright signal areas in the
      epiphysis, gray signal areas in the epiphysis, and fuzzy joint surface of the
      epiphysis of the femur and tibia. Detailed inspection of the histology specimen
      showed more unfamiliar features of rat knee microanatomy, including curvy or
      dipped surface of the femur/tibia epiphysis, areas composed of a mixture of
      cartilage and bone components, normal notch structure, cyst-like structure, and
      cavity between cortical lamellae under the joint cartilage. CONCLUSION: There are
      a number of normal microstructures of the rat knee joint that can be potentially
      misinterpreted as arthritic changes on MR images. Recognizing these rat knee
      microstructures can help correct image reading during biomedical research.

PMID- 19863416
TI  - T2 relaxation time mapping of proximal tibiofibular cartilage by 3-tesla magnetic
      resonance imaging.
AB  - BACKGROUND: The proximal tibiofibular joint (PTFJ) can be considered the fourth
      compartment of the knee joint. However, there have been no studies of the T2
      values (T2 relaxation time) of PTFJ cartilage. PURPOSE: To assess the T2 values
      of PTFJ cartilage at 3T magnetic resonance imaging (MRI), and to show the
      clinical utility of T2 values of PTFJ cartilage for the diagnosis of
      osteoarthritis (OA). MATERIAL AND METHODS: 118 patients who had knee MR imaging
      and knee radiography were enrolled. MRI was performed using a 3T MRI scanner, and
      T2 maps were calculated from a sagittal multi-echo acquisition. Two regions of
      interest (ROIs) were positioned within PTFJ cartilage and medial femoral condyle
      (MFC) cartilage. The average T2 value and standard deviation (SD) of each ROI
      were recorded. Using PTFJ cartilage as a standard reference, the T2 index
      ((MFC/PTFJ)x100) and T2(SD) index ((MFC(SD)/PTFJ(SD))x100) were calculated. A
      paired t test was performed to compare the mean and SD of ROIs within PTFJ and
      MFC cartilage. Correlation analyses were performed among the parameters age,
      Kellgren-Lawrence (KL) score, means and SDs of ROIs within PTFJ and MFC
      cartilage, T2 index, and T2(SD) index. RESULTS: PTFJ cartilage had a
      significantly shorter T2 value than did MFC cartilage (P<0.0001). ROIs within
      PTFJ cartilage showed significantly smaller SDs than did those within MFC
      cartilage (P<0.0001). The average T2 value and SD of MFC and the T2(SD) index
      showed a positive correlation to the KL score (P<0.05). The correlation
      coefficients for the average T2 value, SD, and T2(SD) index of MFC were R=0.203,
      0.254, and 0.268, respectively. However, there was no significant correlation
      between T2 values of PTFJ cartilage and KL score (P=0.643). CONCLUSION: PTFJ
      cartilage showed shorter and more homogeneous T2 values with a small SD than did
      MFC cartilage, regardless of the degree of OA at femorotibial compartments. PTFJ
      cartilage may be a useful internal standard reference to diagnose OA and would be
      a good candidate as a standard reference for cartilage imaging.

PMID- 19863417
TI  - Tears of the supraspinatus tendon: assessment with indirect magnetic resonance
      arthrography in 67 patients with arthroscopic correlation.
AB  - BACKGROUND: Magnetic resonance (MR) arthrography is generally regarded as the
      gold standard for shoulder imaging. As an alternative to direct MR arthrography,
      the less invasive indirect MR arthrography technique was proposed, offering
      logistic advantages because fluoroscopic or ultrasonographic guidance for joint
      injection is not required. PURPOSE: To assess the diagnostic performance of
      indirect MR arthrography in the diagnosis of full- and partial-thickness
      supraspinatus tears in a symptomatic population. MATERIAL AND METHODS: Two
      radiologists with different levels of experience independently and
      retrospectively interpreted indirect MR (1.5T) arthrograms of the shoulder
      obtained in 67 symptomatic patients who underwent subsequent arthroscopy. On MR,
      the supraspinatus tendon was evaluated for full- or partial-thickness tear. With
      arthroscopy as the standard of reference, sensitivity, specificity, and
      diagnostic accuracy of indirect MR arthrography in the detection of full- and
      partial-thickness tears of the supraspinatus tendon was calculated. Kappa (kappa)
      statistics were used for the assessment of the agreement between arthroscopic and
      imaging findings and for the assessment of interobserver agreement. RESULTS: For
      full-thickness tears of the supraspinatus tendon, sensitivities, specificities,
      and accuracies exceeded 90% for both observers, with excellent interobserver
      agreement (kappa = 0.910). For partial-thickness tears, sensitivities (38-50%)
      and accuracies (76-78%) were poor for both reviewers, and interobserver agreement
      was moderate (kappa = 0.491). Discrepancies between MR diagnosis and arthroscopy
      were predominantly observed with small partial-thickness tears. CONCLUSION:
      Indirect MR arthrography is highly accurate in the diagnosis of full-thickness
      rotator cuff tears. However, the diagnosis of partial-thickness tears with
      indirect MR arthrography remains faulty, because exact demarcation of
      degenerative change and partial rupture is difficult. On the basis of the above
      findings, we do not recommend indirect MR arthrography on patients for whom
      rotator cuff disease is suspected clinically.

PMID- 19863418
TI  - Diagnostic value of multislice computed tomography and magnetic resonance imaging
      in the diagnosis of retroperitoneal spread of testicular cancer: a literature
      review.
AB  - Testicular cancer is the most frequent malignant disorder in men aged 15-35
      years. Generally, diagnosing and follow-up include computer tomography (CT)
      examinations to detect possible retroperitoneal spread (abdomen and pelvis),
      resulting in at least eight CT examinations. This patient group is thereby
      exposed to a non-neglectable radiation dose, increasing the risk of future
      radiation-induced secondary cancer. This is especially problematic in potentially
      surgically cured patients with stage 1 testicular cancer. Thus, it can be
      beneficial to substitute CT with magnetic resonance imaging (MRI), provided there
      is valid evidence that the diagnostic value of MRI is at least comparable to
      current multislice CT (MSCT). The purpose of this study was to analyze whether
      there is evidence to recommend a substitution of MSCT with MRI in the diagnosis
      of retroperitoneal spread of testicular cancer. A literature search on the
      diagnostic accuracy, specificity, and sensitivity of MSCT and MRI in the
      diagnosis of retroperitoneal spread of testicular cancer was performed in the
      following databases: PubMed, EmBase, and ISI Web of Science. The search was
      limited to include the period from 2000 to September 2008, and to human and
      English-language publications. Forty-four publications were obtained for formal
      review (27 from PubMed, 15 from EmBase, two from ISI Web of Science). None of the
      publications reviewed encompassed diagnostic specificity and sensitivity of MSCT,
      and they lacked systematic comparison of MSCT and MRI. Only one study included
      sensitivity and specificity of MRI compared to single-slice CT. Both methods had
      a sensitivity and a specificity of approximately 70%. The literature review did
      not reveal valid data regarding diagnostic accuracy of MRI compared with MSCT for
      diagnosing retroperitoneal spread of testicular cancer. A prospective blinded
      comparative study is needed to provide valid evidence.

PMID- 19863419
TI  - Comparison of computed tomography histogram analysis and chemical-shift magnetic
      resonance imaging for adrenal mass characterization.
AB  - BACKGROUND: Computed tomography (CT) histogram analysis and chemical-shift
      magnetic resonance imaging (MRI) are currently used modalities for adrenal mass
      characterization. However, it is not yet clear which modality can be regarded as
      most sensitive in terms of adrenal mass characterization. PURPOSE: To
      prospectively compare CT histogram analysis and chemical-shift MRI in the
      characterization of adrenal masses. MATERIAL AND METHODS: Between May 2007 and
      November 2008, 93 patients (45 males, 48 females; mean age 56.7 years, range 22
      85 years) with 109 adrenal masses prospectively underwent both unenhanced CT and
      chemical-shift MRI examinations. These masses consisted of 67 adenomas and 42
      metastases. Histogram analysis was applied with a circular region of interest
      (ROI) that recorded mean attenuation, total number of pixels, number of negative
      pixels, and the percentage of negative pixels on unenhanced CT images for each
      adrenal mass. In the CT histogram analysis, a 10% negative pixel threshold for
      unenhanced CT was calculated. In chemical-shift MRI, signal intensity drop
      between in-phase and opposed-phase images was quantitatively calculated so that
      adrenal-to-spleen chemical-shift ratios and adrenal signal intensity indexes were
      determined for each of the adrenal masses. A mass was regarded as an adenoma if
      it contained more than 10% negative pixels by CT histogram analysis, showed an
      adrenal-to-spleen chemical-shift ratio of less than 0.71, and had an adrenal
      signal intensity index of more than 16.5% by chemical-shift MRI. The results were
      compared to reveal which method was most sensitive in the diagnosis of adrenal
      masses and whether or not a correlation exists between these two modalities.
      Final diagnoses were based on imaging follow-up of minimum 6 months, biopsy,
      surgery, and adrenal washout study. RESULTS: On unenhanced CT examinations, all
      of the 67 adenomas and 21 out of 42 metastases exhibited negative pixels. None of
      the metastases showed more than 10% negative pixels on CT histogram analysis. An
      increase in the percentage of negative pixels correlated well with a decrease in
      the mean CT attenuation. CT histogram analysis using a 10% negative pixel
      threshold gave a 91% sensitivity and 100% specificity for the diagnosis of an
      adenoma. On chemical-shift MRI, for an adrenal-to-spleen chemical-shift ratio of
      less than 0.71, a 97% sensitivity and 100% specificity were achieved, while a 97%
      sensitivity and 93% specificity were obtained for an adrenal signal intensity
      index of more than 16.5% for adenoma diagnosis. CONCLUSION: CT histogram analysis
      method using a 10% negative pixel threshold on unenhanced CT had a good
      sensitivity and perfect specificity for the differentiation of adrenal adenomas
      from non-adenomas. In spite of the good results obtained with the CT histogram
      analysis method, chemical-shift MRI using adrenal-to-spleen chemical-shift ratio
      and adrenal signal intensity index formulas had a higher sensitivity and could
      help in the characterization of adrenal masses appearing indeterminate by CT
      histogram analysis.

PMID- 19863420
TI  - Prostate cancer detection: the value of performing an MRI before a biopsy.
AB  - BACKGROUND: In recent years, prostate-specific antigen (PSA) screening has been
      widely performed. As a result, patients who need to undergo a complete physical
      examination for an elevated PSA level have been rapidly increasing. Magnetic
      resonance imaging (MRI) examination has previously been reported to be effective
      for the detection of prostate cancer. PURPOSE: To evaluate the detectability of
      prostate cancer by performing MRI before biopsy, and to evaluate the relationship
      between detectability with MRI and cancer location, Gleason score (GS), and tumor
      size. MATERIAL AND METHODS: MRI was performed at 1.5 Tesla in 122 consecutive
      patients before biopsy. The detectability of prostate cancer, including
      sensitivity and positive predictive value (PPV) of transrectal ultrasonography
      (TRUS), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) (b=2000
      s/mm(2)), apparent diffusion coefficient (ADC) map, and biopsy, was calculated
      using whole-mount section histopathology as a gold standard. In addition, the
      relationship between the detectability on each MRI sequence and factors such as
      cancer location (peripheral zone vs. transition zone), GS 5-10, short-axis
      diameter (< or =4 mm, 5-9 mm, > or =10 mm), and long-axis diameter (< or =9 mm,
      10-19 mm, > or =20 mm) were also evaluated. RESULTS: The sensitivities of TRUS,
      T2WI, DWI, ADC map, and biopsy were 26.9%, 41.2%, 56.7%, 57.7%, and 75.1%,
      respectively, and the PPVs of those modalities were 73.0%, 83.0%, 86.4%, 87.2%,
      and 91.5%, respectively. There was no correlation between the sensitivity of each
      MRI sequence and cancer location. The sensitivity of each MRI sequence increased
      as GS and short- and long-axis diameters of cancer lesions increased. CONCLUSION:
      MRI before a biopsy has a high detectability of prostate cancer, particularly
      with tumor size of more than 5 mm in short-axis diameter or 10 mm in long-axis
      diameter.

PMID- 19863421
TI  - RECIST and targeted therapy.

PMID- 19863422
TI  - Adolescent idiopathic scoliosis may not be associated with brain abnormalities.
AB  - BACKGROUND: The etiology of adolescent idiopathic scoliosis (AIS) is uncertain
      and multifactorial. Recently, regional brain volume differences have been
      reported in the pathogenesis of AIS. PURPOSE: To examine cerebral glucose
      metabolism using (18)F-fluorodeoxyglucose (FDG) brain positron emission
      tomography (PET) in patients with AIS and in gender-matched healthy control
      subjects. MATERIAL AND METHODS: Twenty-six right-handed AIS patients (six male,
      20 female; mean age 14.6+/-2.22 years, range 11-18 years) were prospectively
      recruited for this study. Fourteen young adults (three male, 11 female; mean age
      27+/-1.54 years, range 25-29 years) were included as a control group. Statistical
      parametric mapping (SPM) was used to determine cerebral glucose metabolism.
      Statistical probabilistic anatomical mapping (SPAM) was used to investigate the
      metabolic differences between AIS and normal control subjects with respect to
      previously reported brain areas. RESULTS: SPM analysis showed no voxels with
      differing cerebral glucose metabolism in AIS patients. SPAM analysis revealed no
      significant differences between AIS and normal control subjects. CONCLUSION: SPM
      and SPAM analyses showed no statistically significant differences in cerebral
      glucose metabolism between AIS and normal control subjects. These results may
      suggest that there is no relationship between AIS and brain abnormalities.

PMID- 19863423
TI  - Magnetic resonance imaging findings of ovarian stromal hyperthecosis.
AB  - Ovarian stromal hyperthecosis is characterized by diffuse distribution of
      luteinized stromal cells accompanied by varying degrees of stromal hyperplasia.
      We report a case of ovarian stromal hyperthecosis with particular regard to
      magnetic resonance (MR)-pathologic correlation. At initial MR imaging, the
      central areas of the bilateral ovarian masses showed hypointensity on T1-weighted
      images and hyperintensity on T2-weighted images, while the peripheries of the
      bilateral masses showed isointensity to myometrium on T1-weighted images and
      heterogeneous signal intensities on T2-weighted images. At 15 days after the
      initial MR imaging examination, a second MR imaging demonstrated shrinkage of the
      bilateral ovarian masses. Change in the peripheries to predominantly isointensity
      to myometrium on the T2-weighted images was also observed. The patient underwent
      bilateral oophorectomy. Microscopic examination revealed scattered nests of
      lutein cells on a background of densely proliferated ovarian stroma with minimal
      collagen production in both ovaries. Edema was occasionally seen in the outer
      portion but was marked in the central zone of the ovaries, particularly on the
      left. The final pathologic diagnosis was stromal hyperthecosis. With regard to MR
      pathologic correlation, the MR findings in the peripheries of the bilateral
      masses (isointensity relative to myometrium on both T1- and T2-weighted imaging)
      showed the characteristics of stromal hyperthecosis.

PMID- 19863425
TI  - Intermittent ischaemia of skin flaps shortens time taken to divide pedicles: an
      experimental study in rats.
AB  - Ischaemic preconditioning increases the survival of flaps. Random-pattern
      McFarlane dorsal flaps were raised in 30 female Wistar rats, which were divided
      into three groups. An ischaemic conditioning protocol with clamping of the
      pedicle was used. No clamping was used in the control group, and the pedicle was
      clamped for 15 minutes in the second group and 20 minutes in the third group
      daily to see if the duration of ischaemia had any effects on the viability of the
      flaps. The pedicles were divided earlier in the clamped groups than in the
      control group. The size of necrotic areas of the flaps in the clamped groups was
      smaller than on the control group. Daily postoperative intermittent ischaemic
      conditioning in the pedicles of the flaps had a protective effect on their
      survival and led to earlier division of the pedicles.

PMID- 19863426
TI  - Treatment of transected peripheral nerves with artemin improved motor neuron
      regeneration, but did not reduce nerve injury-induced pain behaviour.
AB  - Incomplete recovery of function and neuropathic pain are common problems after
      peripheral nerve injury. To develop new treatment strategies for peripheral nerve
      injuries we investigated whether the neurotrophic factor artemin could improve
      outcome after sciatic nerve injuries in rats. Artemin is a member of the glial
      cell line-derived neurotrophic factor (GDNF) family and exerts neuroprotective
      effects on sensory neurons as well as influencing behavioural thermal
      sensitivity. We additionally evaluated if fibrin sealant, which is sometimes used
      as a nerve glue, had any effects on neuropathic pain-related behaviour. After the
      sciatic nerve had been transected, 30 animals were randomised to one of three
      groups: treatment with a fibrin sealant that contained artemin in conjunction
      with sutures; fibrin sealant with no artemin (sham) in conjunction with sutures;
      or sutures alone (n=10 in each group). Motor function, sensory function, and
      autotomy were evaluated from 1 to 12 weeks after injury. Retrograde flourogold
      tracing 12 weeks after injury showed that the addition of artemin increased the
      number of regenerating motor neurons. However, it did not improve their
      performance, as measured by the Sciatic Function Index, compared with sham or
      suture alone. Animals treated with artemin had a non-significant increase in
      motor nerve conduction velocity compared with sham. However, artemin did not
      reverse nerve injury-induced pain behaviour such as cold or heat
      hypersensitivity. Fibrin sealant in itself did not ameliorate motor performance,
      or regeneration of motor neurons, or give rise to nerve injury-induced pain
      behaviour. The results indicate that artemin is of value as a treatment for
      peripheral nerve injuries, although the effects were limited. As the artemin high
      affinity receptor GFRalpha-3 is present in Schwann cells and not in motor
      neurons, the effect on motor neuron axon regeneration may result from an indirect
      effect through Schwann cells in the injured nerve.

PMID- 19863427
TI  - Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and
      FGFR3 in families with BRCA1/2-negative breast cancer.
AB  - Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It
      is an autosomal dominantly inherited disorder with variable expression that is
      caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or
      FGFR3 genes. We have previously reported that patients with Saethre-Chotzen
      syndrome have an increased risk of developing breast cancer. Here we have
      analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to
      study whether a proportion of these families might have mutations in Saethre
      Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic
      mutations in the coding sequence in any of the 26 patients. MLPA (multiplex
      ligation-dependent probe amplification)-analysis also showed no alterations in
      copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1,
      TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that
      mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2
      negative patients with hereditary breast cancer.

PMID- 19863428
TI  - Recontouring commissuroplasty after reconstruction of large defects after
      resections for head and neck cancer with commissure involvement using an
      anterolateral thigh flap.
AB  - The aim of this study was to describe our technique for recontouring
      commissuroplasty after reconstruction of large, through-and-through perioral
      defects in patients with head and neck cancer with emphasis on functional and
      cosmetic outcome. This technique was used in 15 patients aged between 33 and 66
      years. Recontouring required liposuction, arrow-headed advancement flap, and
      anchoring vector sutures. All patients had satisfactory functional and cosmetic
      results and healed without complication. Function was evaluated to find out
      whether the patient was free of drooling and able to accommodate more food
      postoperatively. Aesthetic evaluation was subjective, and the patients themselves
      decided using a visual analogue cosmesis scale. Our combined procedures provide a
      predictable way of creating a new oral commissure, improving postoperative
      drooling, and increasing the intraoral space after reconstruction.

PMID- 19863429
TI  - Referral of sensation to an advanced humanoid robotic hand prosthesis.
AB  - Hand prostheses that are currently available on the market are used by amputees
      to only a limited extent, partly because of lack of sensory feedback from the
      artificial hand. We report a pilot study that showed how amputees can experience
      a robot-like advanced hand prosthesis as part of their own body. We induced a
      perceptual illusion by which touch applied to the stump of the arm was
      experienced from the artificial hand. This illusion was elicited by applying
      synchronous tactile stimulation to the hidden amputation stump and the robotic
      hand prosthesis in full view. In five people who had had upper limb amputations
      this stimulation caused referral touch sensation from the stump to the artificial
      hand, and the prosthesis was experienced more like a real hand. We also showed
      that this illusion can work when the amputee controls the movements of the
      artificial hand by recordings of the arm muscle activity with electromyograms.
      These observations indicate that the previously described "rubber hand illusion"
      is also valid for an advanced hand prosthesis, even when it has a robotic-like
      appearance.

PMID- 19863430
TI  - Sights of touching activates the somatosensory cortex in humans.
AB  - We report our observations of cross-modal interactions between sight and touch
      using functional magnetic resonance imaging (fMRI). Experiments were devised to
      show that sight and touch are linked in a cross-modal arrangement, and two
      separate experiments were done in an MRI scanner. In the first, the subject's
      right hand was stimulated with a brush; in the second, a video sequence was
      presented to the subject inside the scanner through video goggles in visual three
      dimensional stereo, showing one brushstroke every second on a hand in the same
      manner as the subject had just previously experienced. The result was that both
      the primary and the secondary somatosensory cortexes were activated in the
      participants when the hands were touched, and when the subjects saw only a hand
      being touched in the same manner. The results indicated cross-modal links between
      sight and touch of the hand in humans.

PMID- 19863431
TI  - Combined fixation with plates and transmalar Kirschner wires for zygomatic
      fractures.
AB  - After repair of a fractured zygoma, the fixed zygoma occasionally becomes
      displaced. This phenomenon--generally called "relapse"--is a complication that
      can be prevented by fixing plural sites with plates. However, this impairs blood
      supply to the bone, which causes atrophy. To solve this dilemma, we developed a
      new concept for fixing the zygoma. Fractured zygomas are fixed by combining plate
      fixation at a single site with transmalar fixation with Kirschner wires. This
      secures stability of the fixed zygoma without impairing its blood supply. We
      evaluated the stability of fractured zygomas fixed by our method by doing dynamic
      experiments using simulation models. The stresses at the screw-bone interfaces
      were significantly reduced by the additional transmalar fixation with wire,
      indicating that zygomas fixed by our method are less likely to relapse than
      zygomas fixed with a single plate. We also reviewed the outcomes of patients
      treated by our method, which indicates its clinical usefulness.

PMID- 19863432
TI  - Operative treatment of enchondromas of the hand: is cancellous bone grafting
      necessary?
AB  - Curettage is the treatment of choice for enchondromas, the most common primary
      tumour of the hand. In contrast, additional bone grafting remains controversial.
      Between 1998 and 2004, we operated on 22 patients with monostotic enchondroma of
      the hand. Sixteen patients (eight of whom had no additional bone grafting, and
      eight who had) were evaluated at a mean of 68 (range 42-108) months (no) and 50
      (range 29-65) months (bone grafts) postoperatively. Bone density was measured
      densitometrically on the radiographs, and the groups were compared with each
      other and within themselves with corresponding locations on the healthy opposite
      hand. Neither bone density nor functional results were significantly different.
      Additional bone grafting in the treatment of enchondromas is not necessary and
      should be reserved for particular indications.

PMID- 19863433
TI  - Extensive perineal and pelvic defects reconstructed simultaneously using
      bilateral pedicled gracilis and rectus abdominis muscle flaps after en-bloc
      excision of locally invasive perineal mucinous adenocarcinoma 1.
AB  - We report a case of successful simultaneous reconstruction of pelvic and perineal
      defects using bilateral pedicled gracilis and inferiorly based rectus abdominis
      muscle flaps after en-bloc excision of the tumour and abdominoperineal resection
      of locally advanced invasive perineal mucinous adenocarcinoma originating from a
      chronic anal fistula.

PMID- 19863434
TI  - Chondroid syringoma of the hand.
AB  - Chondroid syringoma is a rare cutaneous tumour that usually arises in the head
      and neck region and is rarely seen on the hands; it is rarely malignant at sites
      other than the head and neck. However, it should be included in the differential
      diagnosis of tumours of the hand. We present a 56-year-old man with a chondroid
      syringoma of the hand that clinically resembled a vascular tumour.

PMID- 19863435
TI  - Squamous cell carcinoma in bilateral untreated syndactyly.
AB  - We present an 81-year-old man with untreated bilateral syndactyly. Hand function
      and cosmesis did not concern him but long-term use of the hand resulted in
      chronic skin changes from friction, and the subsequent development of a squamous
      cell carcinoma.

PMID- 19863436
TI  - Acute cardiac care--from symptoms to diagnosis and to interventions.

PMID- 19863437
TI  - Immunosuppressive signature of cutaneous Mycobacterium ulcerans infection in the
      peripheral blood of patients with buruli ulcer disease.
AB  - Buruli ulcer disease (BUD) is an emerging human disease caused by infection with
      Mycobacterium ulcerans, which leads to the development of necrotic skin lesions.
      The pathogenesis of the ulcer is closely associated with the production of
      mycolactone, a diffusible cytotoxin with immunomodulatory properties. To identify
      immunological correlates of BUD, we performed a broad screen of inflammatory
      mediators in serum samples and stimulated whole-blood supernatants of patients.
      We found that patients with active ulcers displayed a distinctive profile of
      immune suppression, marked by the down-modulation of selected chemokines and an
      impaired capacity to produce Th1, Th2, and Th17 cytokines on stimulation with
      mitogenic agents. These immunological defects were induced early in the disease
      and resolved after anti-BUD therapy, establishing their association with the
      presence of M. ulcerans. Interestingly, some of the defects in cytokine and
      chemokine response could be mimicked in vitro by incubation of CD4(+) peripheral
      blood lymphocytes with mycolactone. Our findings support the hypothesis that
      mycolactone contributes to bacterial persistence in human hosts by limiting the
      generation of adaptive cellular responses. Moreover, we identified immunological
      markers of BUD, which may be helpful for confirmatory diagnosis of the disease
      and, especially, for monitoring the response to antibiotic treatment.

PMID- 19863438
TI  - Tetraacylated lipopolysaccharide of Yersinia pestis can inhibit multiple Toll
      like receptor-mediated signaling pathways in human dendritic cells.
AB  - BACKGROUND: Yersinia pestis, the causative agent of plague, showed a temperature
      dependent change in lipid A composition, with a reduced degree of acylation when
      bacteria were grown at 37 degrees C (tetraacylated) versus ambient temperature
      (hexaacylated). METHODS: Human monocytes and monocyte-derived dendritic cells
      (DCs) were exposed to Y. pestis grown at 26 degrees C or 37 degrees C, to their
      corresponding lipopolysaccharides (LPS-26 degrees C or LPS-37 degrees C), and to
      ligands of different Toll-like receptors (TLRs), such as LPS from Escherichia
      coli (TLR4), lipoprotein (TLR2), polyinosinic-polycytidylic acid (poly-IC)
      (TLR9), and their combinations. Production of cytokines was measured, along with
      expression of surface markers of DC maturation. RESULTS: Y. pestis grown at 37
      degrees C or LPS-37 degrees C induced much lower production of cytokines (such as
      tumor necrosis factor alpha and interleukins 1beta, 10, and 12) by DCs than did
      Y. pestis grown at 26 degrees C or LPS-26 degrees C. Expression of the surface
      markers HLA-DR, CD86, and CD40 by DCs was also reduced in response to treatment
      with LPS-37 degrees C compared with LPS-26 degrees C. Pretreatment of DCs with
      LPS-37 degrees C inhibited subsequent stimulation with LPS-26 degrees C, control
      LPS from E. coli, lipoprotein, or poly-IC. CONCLUSIONS: LPS-37 degrees C can
      inhibit stimulation of DCs not only via TLR4 signaling but also via TLR2 and
      TLR3. [corrected]

PMID- 19863439
TI  - Early sexual experiences and risk factors for bacterial vaginosis.
AB  - BACKGROUND: We have undertaken a cross-sectional study that investigates the
      association between bacterial vaginosis (BV) and sexual practices in sexually
      experienced and inexperienced women. METHODS: Participants were 17-21-year-old
      females who attend Melbourne University, Australia. Study kits that contained an
      information and consent form, questionnaire, swab, and slide were distributed.
      Information regarding demographic characteristics and a broad range of sexual
      practices were collected. Gram-stained, self-collected vaginal smears were scored
      with the Nugent method. Associations between BV and behaviors were examined by
      univariate and multivariate analysis. RESULTS: BV was diagnosed in 25 (4.7%) of
      528 women (95% confidence interval [CI], 3.1%-6.9%). Importantly, BV was not
      detected in women (n = 83) without a history of coital or noncoital sexual
      contact (0%; 95% CI, 0%-4.3%). BV was detected in 3 (3.8%) of 78 women (95% CI,
      0.8%-10.8%) with noncoital sexual experience only and in 22 (6.0%) of 367 women
      (95% CI, 3.8%-8.9%) who reported penile-vaginal sex. BV was associated with a
      history of any genital contact with a sexual partner (P=.02). BV was strongly
      associated with >3 penile-vaginal sex partners in the prior year (adjusted odds
      ratio, 7.1; 95% CI, 2.7-18.4) by multivariable analysis. CONCLUSIONS: This study
      shows a strong association between BV and penile-vaginal sex with multiple
      partners but found no BV in sexually inexperienced women, once a history of
      noncoital sexual practices was elicited. Our findings indicate that BV is not
      present in truly sexually inexperienced women.

PMID- 19863440
TI  - Bacterial vaginosis: are we coming full circle?

PMID- 19863441
TI  - Infection with Mycobacterium tuberculosis Beijing genotype strains is associated
      with polymorphisms in SLC11A1/NRAMP1 in Indonesian patients with tuberculosis.
AB  - Differences in host immune genes may predispose to tuberculosis caused by
      particular Mycobacterium tuberculosis genotypes. We examined this hypothesis in
      Indonesia by spoligotyping M. tuberculosis isolates recovered from 336 patients
      with pulmonary tuberculosis and typing the patients' SLC11A1 gene (formerly known
      as "NRAMP1"), which is involved in susceptibility to tuberculosis. The M.
      tuberculosis Beijing genotype, which comprised 29.8% of all isolates, was
      strongly associated with 2 polymorphisms in SLC11A1: the D543N G allele (odds
      ratio [OR], 2.15; P=.005) and the 3' untranslated region (3'UTR)
      insertion/insertion genotype (OR, 2.5; P=.001). This finding supports the
      hypothesis of coevolution of M. tuberculosis and the human immune system.

PMID- 19863442
TI  - Rationale against preoperative screening for HIV in Polish hospitals: a
      prevalence study of anti-HIV in contrast to anti-hepatitis C virus and hepatitis
      B surface antigen.
AB  - We describe the prevalence of anti-human immunodeficiency virus (anti-HIV) among
      a sample of 1,652 surgical and gynecologic patients in Polish hospitals,
      contrasting it with the prevalence of hepatitis B surface antigen (HBsAg) and
      anti-hepatitis C virus (anti-HCV) to assess the rationale for preoperative
      testing. No anti-HIV-positive samples were found; the prevalence of anti-HCV was
      0.9%, slightly higher than the prevalence of HBsAg of 0.6%. Universal
      preoperative screening of hospital patients for HIV is currently not warranted
      according to the Centers for Disease Control and Prevention guidelines. However,
      the seroprevalence of HIV should be reassessed periodically.

PMID- 19863443
TI  - Prevalence of parvovirus B19 and human bocavirus DNA in the heart of patients
      with no evidence of dilated cardiomyopathy or myocarditis.
AB  - BACKGROUND: Although the DNA of parvovirus B19 (B19V) is frequently detected in
      patients with dilated cardiomyopathy or myocarditis, whether the parvovirus
      causes disease is questionable, since even in healthy individuals the virus
      persists in various tissues. The same question applies to human bocavirus (HBoV).
      We have determined the prevalence and quantity of B19V and HBoV DNA in heart
      tissue of patients who were not experiencing virus-related heart diseases and
      analyzed whether the seroprevalence corresponded to DNA prevalence in the heart.
      METHODS: Samples of left-atrium heart tissue and serum were obtained from 100
      patients who underwent open-heart surgery. Serum immunoglobulin (Ig) G and IgM
      against proteins encoded by B19V and HBoV were detected by enzyme-linked
      immunoabsorption assay and immunoblotting. B19V and HBoV DNA concentrations were
      determined by quantitative real-time polymerase chain reaction (PCR) in heart
      tissue and serum samples. Nested PCRs for VP1, K71, and GT3 identified the B19V
      genotypes. RESULTS: The prevalences of serum IgG specific for B19V and HBoV were
      85% and 96%, respectively. Of all the patients, 85% had B19V DNA detected in
      heart tissues, and 4% displayed low-level B19V viremia, whereas only 5% of heart
      tissue samples and none of the serum samples demonstrated HBoV DNA. The
      sensitivity of B19V serological testing for B19V DNA in heart samples was 0.96
      (95% confidence interval, 0.92-1.0). Specificity was 0.8 (95% confidence
      interval, 0.6-1.0), and the positive predictive value was 0.96 (95% confidence
      interval, 0.92-1.0). B19V genotypes 1 and 2 were present in 11% and 89% of heart
      tissues samples, respectively. B19V genotype 3 was not detected in any of the
      samples. CONCLUSIONS: Our data suggest that B19V but not HBoV demonstrates a
      lifelong persistence in the heart. The detection of B19V DNA in heart tissue
      showed no correlation with clinical symptoms. We strongly recommend that
      serological testing become a standardized procedure for future studies, to obtain
      representative data concerning the prevalence of B19V in the heart.

PMID- 19863445
TI  - Cushing's syndrome in an infant secondary to malignant adrenocortical tumors with
      somatic mutation of beta-catenin.
AB  - A role of beta-catenin (CTNNB1) in the molecular pathogenesis of adrenocortical
      carcinoma (ACC) has been suspected in adult ACC and pediatric pigmented nodular
      adrenocortical disease, but it has never been reported in pediatric ACC. We
      present the case of a 4-month-old Thai infant who had Cushing's syndrome
      secondary to bilateral adrenal tumors with hepatic metastasis. The child was
      successfully treated with a bilateral adrenalectomy and wedge resection of the
      liver nodule. Histopathology revealed bilateral adrenocortical tumors with
      different histologic grades; the right tumor had a higher score, according to
      modified Weiss criteria. On molecular study, a deletion mutation of beta-catenin
      involving codons 44 to 45 was detected in the right adrenal tumor. The same
      mutation was found in peripheral blood before treatment; this mutation
      disappeared after tumor removal. The left tumor harbored wild-type beta-catenin.
      Immunohistochemistry showed nuclear accumulation of beta-catenin on the right
      adrenal tumor and the metastatic nodule. In summary, we present evidence that
      supports the role of the Wnt-signaling pathway in the carcinogenesis of pediatric
      adrenocortical carcinoma.

PMID- 19863444
TI  - The anatomy of a novel malformation of the cardinal vein system.
AB  - Anomalies of the cardinal vein system (CVS) are uncommon but if unidentified can
      lead to life-threatening complications. We report a case with a novel
      malformation of the CVS. Autopsy with in situ dissection of heart and large
      vessels in a 25-day-old infant was performed. The infant was diagnosed with
      congenital heart disease, and systemic venous malformations were suspected by
      imaging. Correlation between premortem imaging and postmortem anatomy was
      performed. The superior and inferior left venous systems developed abnormally. A
      persistent left superior vena cava (PLSVC) drained into the right atrium via the
      coronary sinus. A persistent left inferior vena cava (PLIVC) continued with the
      hemiazygos vein (HV), which drained into the PLSVC. The innominate vein was
      absent. The left renal vein was connected to the HV. Two common iliac veins were
      identified. The left drained into the PLIVC and the right into the right inferior
      vena cava (IVC). Perinatal echocardiography identified only the dilated HV
      draining to an LSVC and a small IVC. Congenital heart disease included
      hypoplastic left ventricle with hypoplastic aortic arch and subaortic stenosis,
      which were diagnosed by fetal ultrasound. Remodeling of components of CVS takes
      place during development, and unknown mechanisms guide this process. Defects of
      this process can lead to variable malformations, as demonstrated by this case. To
      our knowledge, the combination of complex malformations of both superior and IVC
      systems that extends to the common iliac veins has not been reported. We
      recommend identifying vascular anomalies in situ during autopsy before anatomic
      relationships are altered.

PMID- 19863446
TI  - Infant anaplastic large cell lymphoma with hemophagocytic syndrome.
AB  - Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive,
      is uncommon in infancy. We present an unusual occurrence of infant ALCL, ALK
      positive, associated with hemophagocytic syndrome. To the best of our knowledge,
      there have been no cases of infant ALCL, ALK-positive, described that have been
      associated with hemophagocytic syndrome. Particularly in this age group, primary
      hemophagocytic syndrome is also a consideration, which raises particular
      differential diagnostic considerations.

PMID- 19863447
TI  - Eosinophilic/T-cell chorionic vasculitis and intrauterine fetal demise at 34
      weeks: case report and review of the literature.
AB  - Eosinophilic/T-cell chorionic vasculitis is a rare form of chorionic vasculitis.
      A multifocal form of eosinophilic/T-cell chorionic vasculitis is presented
      involving chorionic vessels radiating away from the amniotic fluid, without
      associated chorioamnionitis. There was, however, an associated fetal demise.

PMID- 19863448
TI  - Bone marrow findings at diagnosis in patients with multisystem langerhans cell
      histiocytosis.
AB  - This study was designed to describe the bone marrow features of multisystem
      Langerhans cell histiocytosis (LCH) at diagnosis in patients with or without
      hematologic dysfunction. A retrospective review of bone marrow biopsies from
      patients with multisystem LCH was performed. Cases were diagnosed at the Garrahan
      Hospital between 1987 and 2004. Routine and immunohistochemistry techniques
      (hematoxylin-eosin, periodic acid-Schiff, Giemsa, Gomori reticulin, and CD1a,
      CD68, and CD61) were evaluated. Clinical outcome and laboratory data were
      obtained from the medical charts. Twenty-two bone marrow biopsies from patients
      with multisystem LCH were reviewed at onset of disease. Four patients had no
      hematologic dysfunction and the other 18 patients had monocytopenia (9),
      bicytopenia (7), or tricytopenia (2). Increased number and dysplasia of
      megakaryocytes were evident in 22/22 samples and emperipolesis was present in
      21/22 (95%). Aggregates of histiocytes and hemophagocytosis were seen in 9/22
      samples. Myelofibrosis was found in 16/17 (94%) evaluable samples at diagnosis.
      No association of myelofibrosis and cytopenias or clinical outcome was found.
      Positive CD1a confirmed the presence of LCH cells in 3/22 (14%) samples.
      Hemophagocytosis and poor outcome were significantly more common in patients with
      bilineage and trilineage cytopenias. Langerhans cell histiocytosis cells were
      rarely seen in the bone marrow of these patients (14%); increased histiocytes and
      hemophagocytosis were more commonly found (41%). Hemophagocytosis was associated
      with severe cytopenias. Bicytopenia and tricytopenia were associated with poor
      outcome (death). Myelofibrosis, megakaryocytic dysplasia, and emperipolesis were
      common findings.

PMID- 19863449
TI  - Inflammation-induced preterm birth in a murine model is associated with increases
      in fetal macrophages and circulating erythroid precursors.
AB  - The presence of intrauterine inflammation has been associated with adverse
      neurologic outcomes in preterm infants, but the precise mechanisms of fetal brain
      injury remain unclear. We sought to evaluate inflammatory cell trafficking, fetal
      organ damage, and molecular regulation in the fetoplacental unit using an
      established mouse model of preterm birth associated with intrauterine
      inflammation. Gestational sacs were harvested 6 hours after intrauterine infusion
      of saline or lipopolysaccharide (LPS). Histologic, immunohistochemical, and
      molecular investigations were performed to identify target organ damage and the
      cellular phenotype of inflammatory cells and to quantify circulating inflammatory
      and hematopoietic mediators within the placental and fetal tissue. There was
      widespread increase in fetal macrophages in LPS-exposed pups, including within
      the leptomeninges of the brain, associated with significantly higher of
      interleukin 6 levels in LPS-exposed pups. Although no specific central nervous
      system injury (necrosis or apoptosis) was documented, liver hematomas were seen
      significantly more frequently in LPS-exposed pups. Circulating nucleated fetal
      erythrocytes were also present more frequently with LPS exposure without
      significantly higher erythropoietin levels than saline-exposed mice. The presence
      of increased macrophages, increased circulating interleukin 6 levels, and
      increased circulating erythroid precursors in LPS-exposed pups suggests that
      these are significant factors associated with potential target organ damage, such
      as liver hematomas, associated with intrauterine inflammation and preterm birth.
      The role of macrophages within the fetal leptomeninges is unclear, but they may
      play an important role in inflammatory-mediated brain damage, and further
      investigation of their significance and potential as therapeutic targets is
      warranted.

PMID- 19863450
TI  - Reduction in Staphylococcus aureus growth and exotoxin production and in vaginal
      interleukin 8 levels due to glycerol monolaurate in tampons.
AB  - BACKGROUND: Staphylococcal menstrual toxic shock syndrome depends on vaginal
      production of exotoxins. Glycerol monolaurate (GML) inhibits Staphylococcus
      aureus exotoxin production in vitro. The purpose of this study was to determine
      whether GML, as a tampon fiber finish, inhibits production of exotoxins and the
      cytokine interleukin 8 (IL-8) during normal tampon use. METHODS: On day 2 of
      menstruation, when vaginal S. aureus counts are high in colonized women, study
      participants exchanged their own preferred tampons, after wearing them for 2-6 h,
      for study tampons with or without GML (assigned randomly and blindly), which they
      then wore for 4-6 h. The women's own tampons and the study tampons with or
      without GML were assayed for S. aureus, the exotoxins toxic shock syndrome toxin
      1 and alpha-toxin, and IL-8. RESULTS: A total of 225 women completed the study.
      S. aureus was present in the tampons of 41 women (18%). Lower numbers of S.
      aureus and the exotoxins were detected in study tampons with or without GML than
      in women's own tampons; lower amounts of the exotoxins were present in study
      tampons with GML than study tampons without GML. The IL-8 level was lower in
      tampons from women without vaginal S. aureus compared with women with S. aureus
      and was lower in study tampons with GML than in study tampons without GML.
      CONCLUSIONS: Tampons that contain GML reduce S. aureus exotoxin production. S.
      aureus increases vaginal IL-8 levels, and GML reduces production of this
      proinflammatory cytokine. These results suggest that GML added to tampons
      provides additional safety relative to menstrual toxic shock syndrome as well as
      benefits for vaginal health generally, thus supporting the addition of GML to
      tampons.

PMID- 19863451
TI  - To build a better mousetrap: pitfalls on the path to improving tampon safety.

PMID- 19863452
TI  - Diagnostic performance of the (1-->3)-beta-D-glucan assay for invasive fungal
      disease.
AB  - BACKGROUND: Diagnosis of invasive fungal disease (IFD) is challenging, and it
      remains a significant cause of morbidity and mortality in immunocompromised
      patients. The (1-->3)-beta-D-glucan (BG) assay may be a useful adjunct, but its
      diagnostic performance is not well characterized. METHODS: We retrospectively
      assessed the diagnostic indices of the BG assay in patients at risk of IFD who
      had a compatible clinical syndrome for the diagnosis of IFD a week after initial
      BG testing and at the end of the hospitalization associated with the first BG
      value. Patients with IFD were classified according to current European
      Organization for Research and Treatment of Cancer-Mycoses Study Group criteria,
      independent of BG results. RESULTS: A total of 1308 BG assays were performed for
      871 patients. One hundred twelve proven or probable IFD cases were diagnosed
      within 1 week after initial testing, and 116 cases were diagnosed by the end of
      hospitalization. Sensitivity of an initial BG level 80 pg/mL for IFD at 1 week
      was 0.64 (95% confidence interval [CI], 0.55-0.73), specificity was 0.84 (95% CI,
      0.81-0.86), the positive likelihood ratio was 3.93 (95% CI, 2.94-5.26), and the
      negative likelihood ratio was 0.43 (95% CI, 0.31-0.59). Albumin, intravenous
      immunoglobulin, and hemodialysis were associated with elevated BG levels in
      patients without IFD (odds ratio, 4.78; 95% CI, 2.59-8.80). After excluding
      patients with these factors, specificity and the positive likelihood ratio of an
      initial BG level 80 pg/mL increased slightly. Empirical systemic antifungal
      treatment did not reduce overall BG sensitivity. Sensitivity was slightly lower
      among patients with hematologic malignancy or stem cell transplantation.
      Consideration of BG results would have increased the diagnostic certainty to
      probable in 54% of possible IFD cases. CONCLUSIONS: BG level appears to be a fair
      diagnostic adjunct for IFD in patients with appropriate pretest probability and a
      suggestive clinical syndrome, especially when checked serially in patients not
      receiving factors associated with an elevated BG level in the absence of IFD.

PMID- 19863453
TI  - Raltitrexed: optimism and reality.
AB  - BACKGROUND: Raltitrexed was developed as a direct and specific inhibitor of
      thymidylate synthase. Early clinical trials showed similar activity to 5
      fluorouracil (5-FU), mainly in metastatic colorectal cancer (MCRC). METHODS:
      Pharmacokinetics are summarized and Phase III adjuvant and MCRC trials of
      raltitrexed are reviewed. RESULTS: Response rates and overall survival with
      raltitrexed in MCRC are equivalent to 5-FU. Pooled analysis showed relapse free
      survival was 1 month longer with 5-FU compared with raltitrexed. Grade 3+
      toxicity rates with raltitrexed compare favorably with 5-FU. Unexpectedly,
      however, treatment-related mortality (TRM) was greater with raltitrexed, mainly
      due to protocol violations. TRM was also greater in the adjuvant trial, leading
      to its discontinuation. In spite of excess TRM, much of which could have been
      avoided, overall survival was the same as with 5-FU. Quality of life was
      variously reported as better or inferior to 5-FU. CONCLUSION: The simple once
      every 3 week regimen of raltitrexed has not fulfilled its promise. Meanwhile, the
      field change in MCRC management has left little space for raltitrexed. Withdrawal
      of the sponsor's support has left raltitrexed without the level of continuing
      investigation afforded to 5-FU. The use of raltitrexed in Canada is limited to
      patients exhibiting intolerance - mucosal, hematological and cardiac - to 5-FU.

PMID- 19863454
TI  - Clinical pharmacology, efficacy and safety of atazanavir: a review.
AB  - BACKGROUND: Atazanavir (ATV) is a potent and safe protease inhibitor (PI)
      initially approved in adult HIV-1 infected patients in combination with other
      antiretroviral drugs with once daily administration. In combination with
      nucleoside reverse transcriptase inhibitors (NRTIs) and boosted with ritonavir,
      it has been established as the preferred initial regimen in published guidelines.
      OBJECTIVE: This article reviews relevant pharmacodynamic, pharmacokinetic,
      efficacy and safety data of ATV, administered boosted with ritonavir or
      unboosted, in comparison with other PIs and/or non-NRTIs, with special focus on
      recent studies. METHODS: Review articles, recent primary literature and
      scientific meeting reports were analyzed. RESULTS: Compared to most PIs with
      similar efficacy, the advantages of ATV are a once daily administration with only
      100 mg ritonavir when boosted, a good gastrointestinal tolerance with limited
      diarrhea, a neutral effect on cholesterol and triglycerides, and a favorable
      resistance profile. However, highly frequent hyperbilirubinemia is observed
      resulting in some cases in clinical jaundice. Unboosted ATV must be cautiously
      used because increased resistances have been described. CONCLUSION: The
      combination of a similar efficacy, a better tolerance and a low pill burden, as
      compared to other PIs, makes boosted ATV one of the best options, in combination
      with NRTIs, in PI-naive HIV-1 infected patients.

PMID- 19863455
TI  - Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal
      women with symptoms of vulvar/vaginal atrophy.
AB  - OBJECTIVE: To evaluate the effects of the tissue selective estrogen complex
      (TSEC) pairing bazedoxifene (BZA) with conjugated estrogens (CE) on sexual
      function and quality of life in postmenopausal women. METHODS: In this 12-week,
      double-blind, placebo-controlled study, postmenopausal, non-hysterectomized women
      (n = 652) with symptoms of moderate to severe vulvar/vaginal atrophy were
      randomized to once-daily treatment with BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg,
      or placebo. The Arizona Sexual Experiences (ASEX) Scale, Menopause-Specific
      Quality of Life (MENQOL) questionnaire, and Menopause Symptoms Treatment
      Satisfaction Questionnaire (MS-TSQ) were secondary measures used to assess the
      effects of BZA/CE on sexual function, menopausal symptoms, and satisfaction with
      treatment, respectively. RESULTS: At week 12, both BZA/CE doses were associated
      with significant improvement in ease of lubrication score from baseline compared
      with placebo (p < 0.05) on the ASEX scale, although there was no difference in
      the change in total score. The MENQOL questionnaire results at week 12 showed
      significant improvements in vasomotor function, sexual function and total scores
      with both BZA/CE doses vs. placebo or BZA 20 mg (p < 0.001). The MS-TSQ results
      showed that BZA/CE-treated subjects reported significantly greater overall
      satisfaction with treatment, as well as satisfaction with control of hot flushes
      during the day and night, effect on quality of sleep, and effect on mood or
      emotions, compared with subjects treated with placebo or BZA 20 mg (all p <
      0.05). CONCLUSION: Treatment with BZA/CE for 12 weeks was shown to significantly
      improve sexual function and quality-of-life measures in symptomatic
      postmenopausal women.

PMID- 19863456
TI  - Obesity, metabolic complications and the menopause: an opportunity for
      prevention.
AB  - The prevalence of obesity is rising dramatically, impacting adversely on health
      and well-being at the menopause and across the lifespan. With menopause,
      abdominal adiposity selectively increases. The impact of obesity and abdominal
      adiposity on chronic disease, including diabetes and cardiovascular disease, is
      significant and quality of life is adversely affected. Yet accurate perception of
      the weight-related health-risk profile is lacking and there is inadequate focus
      on prevention and treatment of obesity and its complications. Research aimed at
      prevention and management of obesity at menopause is limited. Accurate risk
      perception, education and translation programs highlighting obesity risks and
      supporting sustainable lifestyle changes are needed, particularly around
      menopause.

PMID- 19863457
TI  - Inhibition of platelet activation by peptide analogs of the beta(3)-intracellular
      domain of platelet integrin alpha(IIb)beta(3) conjugated to the cell-penetrating
      peptide Tat(48-60).
AB  - Activation of the platelet integrin-receptor alpha(IIb)beta(3) is the final
      pathway of platelet aggregation, regardless of the initiating stimulus. Many
      studies suggest that there are several cytoplasmic proteins such as talin and
      beta(3)-endonexin that bind to N(744)PLY(747) and N(756)ITY(759) motif of the
      beta(3) cytoplasmic tail and play the major role in the receptor activation. In
      this study, we investigated the role of the membrane distal region of human
      beta(3) cytoplasmic tail and specifically the N(743)NPLYKEA(750) and
      T(755)NITYRGT(762) sequence that contains an NXXY motif, in platelet aggregation,
      secretion, alpha(IIb)beta(3) activation (PAC-1 binding) and fibrinogen binding.
      We synthesized two peptides corresponding to the above sequences as well as their
      conjugates with the Tat(48-60) cell-penetrating peptide. The capability of
      conjugates to penetrate the platelet membrane was investigated with confocal
      laser scanning microscopy using carboxyfluorescein (CF)-labeled peptides. Our
      results showed that the conjugated with the Tat(48-60) sequence peptides
      penetrate the platelet membrane and inhibit platelet aggregation in both PRP and
      washed platelets in a dose-dependent manner. The Tat-beta(3)743-750 conjugate
      exhibited similar inhibitory activity in PRP and in washed platelets whereas the
      Tat-beta(3)755-762 conjugate was more potent inhibitor of aggregation in washed
      platelets than in PRP. Both conjugated peptides were also able to inhibit P
      selectin membrane expression as well as PAC-1 and fibrinogen binding to the
      platelets, the Tat-beta(3)755-762 conjugate being more potent than Tat-beta(3)743
      750. The Tat(48-60) peptide and the peptides beta(3)743-750 and beta(3)755-762,
      which were not conjugated to the Tat(48-60) sequence, did not exhibit any
      inhibitory effect on the above parameters. In conclusion, the present study shows
      for the first time that the peptide analogs of the intracellular domain of the
      beta(3) subunit beta(3)743-750 and beta(3)755-762 conjugated to the cell
      penetrating peptide Tat(48-60) are capable of penetrating the platelet membrane
      and expressing biological activity by inhibiting the activation of
      alpha(IIb)beta(3), the fibrinogen binding to the activated receptor as well as
      platelet aggregation. Further studies are necessary to support whether such
      conjugated peptides may be useful tools for the development of potent
      antiplatelet agents acting intracellularly through the platelet integrin
      alpha(IIb)beta(3).

PMID- 19863458
TI  - What impact does pregnancy have on anxiety about health?
AB  - BACKGROUND: A previous study suggests that health anxiety, or preoccupation and
      fears about ill health, is elevated during pregnancy. However, replication of
      this result is needed given several methodological weaknesses of the previous
      research. The current study refined earlier work by assessing health anxiety
      using two distinct measures and comparing scores to a control group and to
      established norms for healthy controls. The relationship of health anxiety to
      background variables such as parity and pregnancy complications was also
      explored. METHODS: A total of 252 women in the third trimester of pregnancy and
      45 similarly aged non-pregnant women completed the Illness Attitudes Scale (IAS)
      and the newly developed Short Health Anxiety Inventory (SHAI). RESULTS: Compared
      to the non-pregnant sample and established scores for healthy controls, health
      anxiety was not elevated during pregnancy. Health anxiety was higher in women who
      experienced complications during pregnancy but was unrelated to other background
      variables. The IAS identified more individuals as health anxious than the SHAI.
      CONCLUSIONS: Contrary to previous research, health anxiety was not elevated
      during pregnancy. The IAS appeared to be susceptible to identifying women as
      health anxious due to greater health care utilization by pregnant women rather
      than higher health anxiety. Clinical recommendations and future directions for
      the assessment of health anxiety are outlined.

PMID- 19863460
TI  - Obesity and endometrial cancer: challenges for public health action.

PMID- 19863462
TI  - Lapatinib in metastatic breast cancer.
AB  - Lapatinib is an oral, small-molecule, dual kinase inhibitor that targets both
      HER2 and the EGF receptor. Lapatinib was approved in June 2008 in Europe for the
      treatment of advanced HER2-positive breast cancer. Promising results in
      trastuzumab-refractory metastatic breast cancer were obtained from Phase I, II
      and III studies in combination with chemotherapy. Diarrhea and rash are the most
      common side-effects and are mostly moderate and treatable. Cardiac toxicity
      occurs rarely and mostly as an asymptomatic and reversible decrease of left
      ventricular ejection fraction. Unlike trastuzumab, some data show that lapatinib
      could cross the blood-brain barrier, with some evidence of activity in treating
      or preventing brain metastases. Its evaluation is actively ongoing, in
      combination with trastuzumab and in the adjuvant setting.

PMID- 19863459
TI  - Reliability of serum and urinary isoflavone estimates.
AB  - Sporadic intake and short half-lives of serum or urinary biomarkers may make
      serum and urinary isoflavones quite unreliable indicators of longer-term dietary
      soy intake. In 26 participants in the Adventist Health Study-2 (AHS-2) we
      obtained two measures of fasting morning serum isoflavones, 1-2 years apart. In
      another 76 subjects we obtained an overnight urine sample and six 24-h dietary
      recalls over a period encompassing the time of the urine sample. Intraclass
      correlations (ICC) values for serum isoflavones were 0.11 (log(daidzein)) and
      0.28 (log(genistein)). Assuming that the correlation (true dietary intake, true
      urinary excretion) <0.90, it is shown that this implies an ICC for urinary
      estimates that exceeds 0.56. As expected, the previous day's soy intake, and its
      timing, influenced the next morning's serum levels. These results suggest that
      fasting morning serum isoflavone estimates will provide a poor index of long-term
      soy intake, but that overnight urinary estimates perform much better.

PMID- 19863463
TI  - Effectiveness of cervical cancer screening at different ages.
AB  - Evaluation of: Sasieni P, Castanon A, Cuzick J: Effectiveness of cervical
      screening with age: population based case-control study of prospectively recorded
      data. BMJ 339, B2968 (2009). In a large case-control study with cases identified
      from centers across the UK and using data from the NHS database (collected
      between 1990 and 2008), investigators evaluated the effectiveness of cervical
      screening with Pap tests, with a particular focus on women aged 20-24 years.
      Screening of these young women had little or no effect on the rates of invasive
      cervical cancer up to 30 years of age. However, screening older women (aged 35-64
      years) was shown to reduce cervical cancer risk by approximately 60-80%. This
      study suggests that the screening age can be safely raised to 25 years without
      causing harm. Along with the information from this study, policymakers should
      consider the harms of screening at different ages as well as the absolute rate of
      cervical cancer in screened and unscreened women of different ages.

PMID- 19863464
TI  - Chronic renal insufficiency, cardiovascular disease and mortality in women: a
      causal relationship or coincidence?
AB  - Evaluation of: Kurth T, de Jong PE, Cook NR, Buring J: Kidney function and risk
      of cardiovascular disease and mortality in women: a prospective cohort study. BMJ
      338, B2769 (2009). The incidence of cardiovascular disease events and
      cardiovascular death in a cohort of 27,939 apparently healthy female health
      professionals over 45 years of age (Women's Health Study) who were stratified by
      estimated glomerular filtration rate (GFR) and followed for 12 years was
      assessed. Women with a GFR less than 60 ml/min/1.73 m(2) demonstrated an
      increased risk of death from cardiovascular disease (HR: 1.68; 95% CI: 1.02-2.79)
      compared with women with a GFR higher than 90 ml/min/1.73 m(2). There was no
      difference in risk when groups with decreased GFR of different ranges were
      compared with the group of women with normal GFR for first cardiovascular
      disease, all-cause mortality, myocardial infarction, stroke, coronary
      revascularization and noncardiovascular death.

PMID- 19863465
TI  - Frequency of migraine and the risk of cardiovascular disease for women: limited
      evidence of an association.
AB  - Evaluation of: Kurth T, Schurks M, Logroscino G et al. Migraine frequency and
      risk of cardiovascular disease in women. Neurology 73, 581-588 (2009). There is
      substantial evidence that migraine with aura (MA) is associated with ischemic
      stroke and myocardial infarction in women. The mechanisms of this association are
      poorly understood. Analysis of data from the Women's Health Study, from 27,798
      women over 45 years of age who were initially free of cardiovascular disease,
      found that women with baseline MA at a frequency of less than monthly had
      increased risk of major cardiovascular disease (HR: 2.28; 95% CI: 1.70-3.07)
      relative to women without migraine, and those who reported MA with a frequency of
      more than weekly had more than four-times the risk of ischemic stroke (HR: 4.25;
      95% CI: 1.36-13.29) compared with those without migraine. Low numbers of outcome
      events in each of the frequency categories and lack of information on migraine
      frequency during follow-up limit the interpretation of these findings, but they
      suggest that frequency of migraine may be a moderating factor in the link between
      MA and cardiovascular disease.

PMID- 19863466
TI  - Diabetes and female sexual health.
AB  - Sexual function in female diabetic patients is much less investigated than in
      males. Empirical studies do not show uniform results, but it appears that
      diabetic women experience more frequent sexual dysfunction in general than age
      matched healthy controls, independent of the sociocultural environment. The most
      frequently cited dysfunctions are desire and arousal disorders, such as
      lubrication difficulties, while orgasmic capacity appears to be less affected.
      Direct pathophysiological effects on lubrication are proven, but the impact on
      mental arousal is unclear. The role of diabetic complications is controversial.
      The comorbidity with depression plays a major role. Individual coping with the
      disease and the quality of the relationship are also contributing factors.
      Patients should be encouraged to talk about their sexual problems, as both
      biomedical and psychosocial factors have to be explored. Therapeutic
      interventions include basic counseling, biomedical treatment of atrophy and
      lubrication difficulties, as well as treatment of comorbidities and/or sex
      therapy.

PMID- 19863467
TI  - Long-term prevention with hormone-replacement therapy after the menopause: which
      women should be targeted?
AB  - For decades, hormone-replacement therapy (HRT) was considered safe and was the
      first choice in prevention of postmenopausal osteoporosis induced by estrogen
      deficiency. Numerous experimental and epidemiological studies further supported a
      protective effect of exogenous female sex hormones on atherogenesis and coronary
      heart disease (CHD) in women after the menopause. However, the fact that these
      promising results were not translated into lower incidences of CHD events in
      hormone-treated women compared with placebo in subsequent, large, randomized
      studies of healthy subjects as well as women with known CHD raised a very intense
      debate concerning the safety of HRT in terms of cardiovascular risk. A critical
      mass of data points toward a protective influence of HRT on cardiovascular
      disease end points in early postmenopausal women, but increased harm in elderly
      women, especially those with abdominal adiposity or metabolic syndrome. Once the
      quasi-hysterical reaction to the largest of the randomized studies (the Women's
      Health Initiative) has abated, a future strategy should be to concentrate on
      identifying those relatively few individuals who are not suitable for HRT, as HRT
      still remains the most thoroughly investigated pharmacological prevention
      strategy of osteoporosis.

PMID- 19863468
TI  - Can pregnant diabetics be treated with glyburide?
AB  - Until the last decade, oral hypoglycemic agents have not been recommended in
      pregnancy owing to fear of their potential adverse fetal effects, including
      teratogenicity and neonatal hypoglycemia. However, the evidence in support of
      these recommendations is weak and is principally based on case series involving
      the use of first-generation sulfonylureas. Studies using a single-cotyledon
      placental model have found glyburide to only minimally cross the placenta, an
      observation that paved the way for a landmark randomized clinical trial that
      found glyburide to be as safe and effective as insulin in the management of
      gestational diabetes mellitus. Still, contradicting results regarding its trans
      placental transfer, lack of adequate data regarding its safety during the first
      trimester and reports of increased neonatal morbidity raise concerns regarding
      the universal application of glyburide as an alternative to insulin therapy in
      diabetic pregnant women. Thus, there is a need for large, randomized, controlled
      trials with adequate power to evaluate the possibility of increased neonatal
      metabolic complications as well as the long-term outcome of infants born to
      mothers treated with glyburide and insulin. Unless future studies refute current
      data regarding the efficacy and safety of glyburide, we believe that, owing to
      its ease of administration, convenience and low cost, glyburide will become the
      first line of medical treatment in patients with gestational diabetes mellitus
      within the next few years.

PMID- 19863469
TI  - Embryonic development and pregnancy test sensitivity: the importance of earlier
      pregnancy detection.
AB  - Embryogenesis research provides information on a time of heightened vulnerability
      in embryo development: the time from conception to the day a woman misses her
      menstrual period. During this period, it is vital for the woman to be aware of
      exposures, behaviors and nutritional factors that could negatively impact the
      developing embryo. This article discusses this critical, often-overlooked window
      of development and will review the various types of teratogens that affect
      pregnancy. Over-the-counter pregnancy tests are widely used to determine
      pregnancy status. Earlier test models detected only the pregnancy hormone human
      chorionic gonadotropin in the urine, but it is now known that there are other key
      forms of human chorionic gonadotropin that are relevant when determining
      pregnancy status. This article will explain why early knowledge of pregnancy
      status is important for both woman and embryo, and the role that patient
      education and pregnancy test choice can have on normal embryonic development.

PMID- 19863471
TI  - Lung cancer: a biologically different disease in women?
AB  - Lung cancer is now the leading cancer killer of women, having surpassed breast
      cancer in 1987. Over 30,000 more US women are expected to die from lung cancer
      than from breast cancer annually. The vast majority of lung cancer cases are
      attributable to smoking, and smoking prevalence rates remain unacceptably high in
      US women. Mounting evidence suggests that there are significant differences in
      lung cancer between the sexes. Although the magnitude of the effect of smoking on
      the development of lung cancer may not be different, smoking appears to have an
      impact on the histology of lung cancer. Hormonal and biologic effects may play a
      role in lung cancer carcinogenesis, and may impact treatment response. A more
      thorough understanding of the biologically different aspects of lung cancer
      across different populations may lead to innovations in prevention and treatment.

PMID- 19863470
TI  - Women and peripheral arterial disease.
AB  - Peripheral arterial disease is a major cause of morbidity and mortality in
      Americans. Without aggressive management of the disease as well as comorbidities
      and risk factors, peripheral arterial disease may progress and place patients at
      risk for amputation of the affected limb. In addition, patients affected by
      peripheral arterial disease are at increased risk for death from both
      cardiovascular and noncardiovascular causes. Although traditionally felt to be a
      disease of Caucasian men, women compose a significant portion of patients with
      peripheral arterial disease, especially among the elderly. Increased prevalence
      of asymptomatic disease in women can lead to delayed diagnosis and treatment.
      Without the appropriate medical and or surgical intervention, women are at risk
      of poor procedural outcomes and increased mortality. This review will focus on
      the differences in peripheral arterial disease based on gender and how these
      differences can affect the presentation, diagnosis and treatment of peripheral
      arterial disease in women.

PMID- 19863472
TI  - Ovarian cancer screening and early detection.
AB  - One of the most challenging issues in gynecologic oncology is the high mortality
      rate of ovarian cancer, largely due to detection of disease in advanced stages.
      Women with early-stage disease have a significantly improved survival rate and
      may not require chemotherapy. Thus, the issues to examine are whether there are
      methods to improve early detection, thereby resulting in a reduction in
      mortality. Several large, randomized, clinical trials have recently completed
      evaluating CA 125 and transvaginal sonography as effective strategies to
      accomplish this goal. These issues and the results of the recent trials will be
      reviewed in this article.

PMID- 19863473
TI  - Fertility issues in women with diabetes.
AB  - Diabetes mellitus Type 1 and Type 2 should be considered in the differential
      diagnosis of menstrual abnormalities and infertility. The reproductive period of
      diabetic women may be reduced due to delayed menarche and premature menopause.
      During the reproductive years, diabetes has been associated with menstrual
      abnormalities, such as oligomenorrhea and secondary amenorrhea. It was found that
      better glycemic control and prevention of diabetic complications improves these
      irregularities and increases fertility rates close to those that are seen in the
      general population. Women with persistent menstrual abnormalities despite
      adequate treatment need to be approached by broader evaluation, which will
      include the examination of the hypothalamic-pituitary-ovarian axis and the
      hormonal status, presence of autoimmune thyroid disease and antiovarian
      autoantibodies, and hyperandrogenism.

PMID- 19863474
TI  - Broken-hearted women: the complex relationship between depression and
      cardiovascular disease.
AB  - The importance of mind-body health relationships has been recognized for decades,
      but only recently has the wider medical and cardiovascular community become
      engaged in understanding and addressing the complex, bidirectional risk
      relationship between cardiovascular disease (CVD) and depression. Furthermore, it
      has become increasingly clear that there are incompletely understood sex
      differences in incidence and outcomes for both conditions that should guide
      treatment and future research efforts. This review will explore the role of
      depression in women as a risk factor for incident CVD, its impact on women
      already suffering from CVD, proposed psychobiologic mechanisms and links, and the
      implications of sex differences on diagnosis and treatment.

PMID- 19863475
TI  - Nutrition and bone: it is more than calcium and vitamin D.
AB  - Unlike pharmacological agents that are taken for proscribed periods of time, food
      and nutrient intakes have the possibility of affecting bone health over the
      entire lifespan. While deficiencies or excesses of individual nutrients have been
      shown to affect bone, it is likely that individual foods or dietary patterns have
      important effects related to skeletal health. While biochemical mechanisms exist
      to relate a deficiency of vitamin K to altered bone metabolism, clinical trials
      related to supplementation of this nutrient have been confusing. It is likely
      that these disparate results are related to the fact that interactions of
      nutrients have not been considered or the possibility that suboptimal nutrient
      status is a marker of poor nutritional status. Vitamin A excess has been
      postulated to be related to high fracture risk; however, it is likely that
      retinol is not the best marker for the proposed interaction. Altering whole food
      patterns, such as the Dietary Approaches to Stop Hypertension diet, have
      demonstrated beneficial effects on bone metabolism. Individuals who select some
      vegetarian patterns may need to consider supplementation with nutrients such as
      calcium and protein. Future studies should center on whole food and dietary
      patterns and their relationship to bone metabolism and fracture risk.

PMID- 19863477
TI  - Safety, tolerability, pharmacokinetics and pharmacodynamics of albiglutide, a
      long-acting GLP-1-receptor agonist, in Japanese subjects with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To investigate safety, pharmacokinetics and pharmacodynamics of
      albiglutide in Japanese subjects with type 2 diabetes mellitus. RESEARCH DESIGN
      AND METHODS: This randomized, single-blind, placebo-controlled study examined
      four doses/dose schedules of subcutaneously (sc) administered albiglutide: 15 mg
      weekly, 30 mg weekly, 50 mg biweekly, and 100 mg monthly (cohorts A-D,
      respectively) in 40 subjects (mean age 54.5 years, mean range of glycosylated
      hemoglobin [HbA(1c)] 7.1-8.3%), over a 4-week treatment period. MAIN OUTCOME
      MEASURES: Safety parameters, including adverse events, clinical laboratory tests,
      vital signs, and 12-lead electrocardiogram; plasma concentrations of albiglutide;
      and pharmacodynamic parameters, including change from baseline and weighted mean
      AUC(0-4) in plasma glucose, glucagon, insulin, and C-peptide levels. CLINICAL
      TRIAL REGISTRATION: NCT00530309. RESULTS: At day 29, mean changes from baseline
      (vs. placebo) in fasting plasma glucose (FPG) were: cohort A, -1.92 mmol/L; B, 
      1.98 mmol/L; C, -1.74 mmol/L; D, -0.73 mmol/L; changes in weighted mean glucose
      AUC(0-4) were: cohort A, -2.86 mmol/L; B, -3.58 mmol/L; C, -2.51 mmol/L; D, -1.44
      mmol/L (for FPG and AUC(0-4), all p < or = 0.002 except 100 mg sc monthly, p =
      NS); changes from baseline HbA(1c) were: cohort A, -0.58%; B, -0.57%; C, -0.63%;
      and D, -0.51% (all p < 0.03). Albiglutide sc had a median half-life of 5.3 days,
      plasma apparent systemic clearance of 68.7 mL/h, and apparent volume of
      distribution of 12.6 L. Incidence of adverse events was low and comparable to sc
      placebo in all albiglutide treatment arms except 100 mg sc monthly, where
      gastrointestinal (GI) adverse events were most common. Limitations of this study
      include the small sample size, short treatment duration, and enrollment of
      predominantly male subjects. CONCLUSIONS: Weekly and biweekly albiglutide
      improved glycemic control and were well-tolerated in Japanese subjects with type
      2 diabetes mellitus.

PMID- 19863478
TI  - Control of the vasculature: pharmacological targets in vascular disease.

PMID- 19863479
TI  - Angiotensin, the hormone to be blocked by antithypertensive drugs, and perhaps
      why they don't work.

PMID- 19863480
TI  - What impact might the economic crisis have on HIV epidemics in Southeast Asia?
AB  - OBJECTIVE: To evaluate the potential impact of the current global economic crisis
      (GEC) on the spread of HIV. DESIGN: To evaluate the impact of the economic
      downturn we studied two distinct HIV epidemics in Southeast Asia: the generalized
      epidemic in Cambodia where incidence is declining and the epidemic in Papua New
      Guinea (PNG) which is in an expansion phase. METHODS: Major HIV-related risk
      factors that may change due to the GEC were identified and a dynamic mathematical
      transmission model was developed and used to forecast HIV prevalence, diagnoses,
      and incidence in Cambodia and PNG over the next 3 years. RESULTS: In Cambodia,
      the total numbers of HIV diagnoses are not expected to be largely affected.
      However, an estimated increase of up to 10% in incident cases of HIV, due to
      potential changes in behavior, may not be observed by the surveillance system. In
      PNG, HIV incidence and diagnoses could be more affected by the GEC, resulting in
      respective increases of up to 17% and 11% over the next 3 years. Decreases in VCT
      and education programs are the factors that may be of greatest concern in both
      settings. A reduction in the rollout of antiretroviral therapy could increase the
      number of AIDS-related deaths (by up to 7.5% after 3 years). CONCLUSIONS: The GEC
      is likely to have a modest impact on HIV epidemics. However, there are plausible
      conditions under which the economic downturns can noticeably influence epidemic
      trends. This study highlights the high importance of maintaining funding for HIV
      programs.

PMID- 19863481
TI  - Two-year efficacy and safety of botulinum a toxin intravesical injections in
      patients affected by refractory painful bladder syndrome.
AB  - INTRODUCTION AND AIM: We report the 2-year efficacy and tolerability of
      intravesical botulinum A toxin (BoNT/A) injections in patients with painful
      bladder syndrome (PBS) associated with increased urinary frequency refractory to
      conventional treatments. MATERIALS AND METHODS: Thirteen women were prospectively
      included in the study. The preliminary assessment included voiding diary,
      urodynamics, urinary tract ultrasound and the visual analog scale (VAS) for pain
      quantification. All patients received multiple injections of 200 U commercially
      available BoNT/A diluted in 20 ml 0.9% NaCl, under cystoscopic guidance. Clinical
      evaluation, urodynamics, urinary tract ultrasound and VAS were repeated at least
      two times per year throughout the follow-up. RESULTS: A total of 58 injections
      were administered with a mean of 4.8 +/- 0.8 injections per patient. The mean
      interval between two consecutive injections was 5.25 +/- 0.75 months. At 1 and 4
      mo follow up ten patients reported a subjective improvement. Mean VAS scores,
      mean daytime and night-time urinary frequency decreased significantly. Nine
      patients at 1 month and seven at the 4-month check-up complained of dysuria. The
      three non-responders to the first intravesical treatment session underwent
      another three months later with satisfactory results. At 1 and 2 years follow up
      the beneficial effects persisted in all patients. We did not observe any systemic
      side effects during the observation time. CONCLUSIONS: Intravesically injected
      BoNT/A is effective and safe in the medium-term management of patients with PBS.
      As the beneficial effect decreased progressively within a few months after
      treatment, repeat injections of the neurotoxin were needed over time.

PMID- 19863482
TI  - Gestational exposure to antidepressants and the risk of spontaneous abortion: a
      review.
AB  - BACKGROUND: Although the relationship between antidepressant use during pregnancy
      and its adverse effects has been widely investigated, very few studies have
      evaluated the impact of antidepressant use during pregnancy on the risk of
      spontaneous abortion. We present an overview of the evidence relating to the
      association between antidepressant use during gestation and the risk of
      spontaneous abortion. METHODS: We systematically searched PubMed and the
      reference lists of all relevant articles, including reviews, published in English
      or French from 1975 through 2009 for studies that examined the association
      between adverse pregnancy outcomes and gestational exposure to antidepressants
      with data on spontaneous abortions. Only etiologic studies were considered.
      RESULTS: Fifteen studies met inclusion criteria. The majority of these were
      prospective cohort studies on tricyclics antidepressants (TCAs) or selective
      serotonin reuptake inhibitors (SSRIs) use during pregnancy. Overall, in
      unadjusted analyses, fluoxetine (OR = 2.0; 95% CI = 1.4 - 3.0) and bupropion (OR
      = 4.1; 95% CI = 1.5 - 11.1) were significantly associated with the risk of
      spontaneous abortion. However, in adjusted analyses, only paroxetine (OR = 1.7;
      95% CI = 1.3 - 2.3) and venlafaxine (OR = 2.1; 95% CI = 1.3 - 3.3) were
      significantly associated with the risk of spontaneous abortion. CONCLUSIONS: This
      review suggests that gestational exposure to antidepressants, especially
      paroxetine and venlafaxine, can lead to spontaneous abortion.

PMID- 19863483
TI  - The potential of polyphosphazenes for delivery of vaccine antigens and
      immunotherapeutic agents.
AB  - Polyphosphazene polyelectrolytes are synthetic, biodegradable polymers that have
      shown great potential in vaccine and drug delivery applications. Numerous
      investigations in laboratory animals have revealed that polyphosphazenes are also
      potent immunological adjuvants that can dramatically enhance the magnitude,
      quality and duration of immune responses to a variety of bacterial and viral
      vaccine antigens. Evidence is accumulating that these polymers have potent
      adjuvant activity in large animals as well. Interestingly, polyphosphazenes can
      be combined with novel immune modulatory agents resulting in even more potent
      immune activity and protection against experimental infection. While most reports
      are on the activity of polyphosphazenes in aqueous formulations, these polymers
      can also be easily made into microparticles, making them especially attractive
      for mucosal delivery. The mechanisms which mediate the adjuvant activity of
      polyphosphazenes are not fully understood, but there is evidence to suggest that
      activation of innate immunity may be involved. Further research and development
      of polyphosphazene adjuvants is warranted to fully explore their potential in the
      delivery of vaccines and immunotherapeutic agents.

PMID- 19863484
TI  - Development of taste masked fast disintegrating films of levocetirizine
      dihydrochloride for oral use.
AB  - Fast disintegrating films of levocetirizine dihydrochloride useful for the
      treatment of acute allergic rhinitis and chronic urticaria have been developed by
      using the taste masking ability of cyclodextrins. The fast disintegrating films
      were prepared by solvent casting method. The films contained water-soluble
      polymers such as Kollicoat IR or pullulan, aspartame and sucralose as sweeteners
      and pre-gelatinized starch as disintegrant. Levocetirizine dihydrochloride was
      incorporated into these films by in-situ complex formation with hydroxy propyl
      beta-cyclodextrin. The optimized films were evaluated for weight variation, film
      thickness, folding endurance, tackiness, tensile strength, assay, content
      uniformity, in vitro disintegration and dissolution, in vivo disintegration and
      taste masking ability by human gustatory sensation test. Results revealed that
      the organoleptic properties of levocetirizine dihydrochloride were improved by
      complexation with hydroxy propyl beta-cyclodextrin and the complex could be
      successfully formulated into a fast disintegrating film.

PMID- 19863485
TI  - A mathematical approach for the simultaneous in vitro spectrophotometric analysis
      of rifampicin and isoniazid from modified-release anti-TB drug delivery systems.
AB  - Dissolution testing with subsequent analysis is considered as an imperative tool
      for quality evaluation of the combination rifampicin-isoniazid (RIF-INH)
      combination. Partial least squares (PLS) regression has been successfully
      undertaken to select suitable predictor variables and to identify outliers for
      the generation of equations for RIF and INH determination in fixed-dose
      combinations (FDCs). The aim of this investigation was to ascertain the
      applicability of the described technique in testing a novel oral FDC anti-TB drug
      delivery system and currently available two-drug FDCs, in comparison to the
      United States Pharmacopeial method for analysis of RIF and INH Capsules with
      chromatographic determination of INH and colorimetric RIF determination.
      Regression equations generated employing the statistical coefficients
      satisfactorily predicted RIF release at each sampling point (R(2)>or=0.9350).
      There was an acceptable degree of correlation between the drug release data, as
      predicted by regressional analysis of UV spectrophotometric data, and
      chromatographic and colorimetric determination of INH (R(2)=0.9793 and
      R(2)=0.9739) and RIF (R(2)= 0.9976 and R(2)=0.9996) for the two-drug FDC and the
      novel oral anti-TB drug delivery system, respectively. Regressional analysis of
      UV spectrophotometric data for simultaneous RIF and INH prediction thus provides
      a simplified methodology for use in diverse research settings for the assurance
      of RIF bioavailability from FDC formulations, specifically modified-release
      forms.

PMID- 19863486
TI  - Preparation, optimisation and characterisation of lyophilised rapid
      disintegrating tablets based on gelatin and saccharide.
AB  - Despite recent success, rapidly disintegrating lyophilized tablets still face
      problems of low mechanical strength and higher disintegration times resulting in
      poor patient compliance. The aim of the current work was to carry out a
      systematic study to understand the factors controlling mechanical properties of
      these formulations. The work investigated the influence of two bloom strengths of
      gelatin: low (60 bloom) and high (225 bloom) at different stock solution
      concentrations (2, 5, 7.5, and 10 %w/w). This was followed by investigation of
      addition of five saccharides (xylitol, glucose, trehalose, maltotriose and
      mannitol) at varied concentration range (10-80 %w/w) to decipher their influence
      on disintegration time, mechanical and thermal properties of the formulation. The
      results indicated that the disintegration time of the tablets dramatically
      decreased by decreasing the concentration and bloom strength of gelatin in the
      stock solution. However the mechanical properties of the tablets were mainly
      influenced by the concentration of gelatin rather than the bloom strength. The
      addition of saccharides resulted in enhancement of tablet properties and was
      concentration dependent. All the saccharides improved the fractubility of the
      tablets significantly at high concentration (equal or higher than 40% w/w).
      However, only high concentration (equal or higher than 40% w/w) of trehalose,
      maltotriose and mannitol significantly enhanced the hardness. Additionally,
      mannitol crytallised during freeze drying and consequently produced elegant
      tablets, whilst the other saccarides exhibited lyoprotectant activity as they
      were able to retain amorphous status. Based on the above findings, an optimized
      formulation was also successfully developed and characterized to deliver 100
      microg dose of Clonidine HCl.

PMID- 19863487
TI  - Formulation of controlled release gellan gum macro beads of amoxicillin.
AB  - Gellan gum has been reported to have wide pharmaceutical applications such as
      tablet binder, disintegrant, gelling agent and as a controlled release polymer.
      Multiparticulate delivery systems spread out more uniformly in the
      gastrointestinal tract and reduce the local irritation. The purpose of this study
      is to explore possible applicability of gellan macro beads as an oral controlled
      release system of a sparingly soluble drug, amoxicillin. Gellan gum beads were
      prepared by ionotropic gelation with calcium ions. The effect of drug loading,
      stirring time, polymer concentration, electrolyte (CaCl2) concentration, curing
      time etc. influencing the preparation of the gellan gum macro beads and the drug
      release from gellan gum beads were investigated in this study. Optimal
      preparation conditions allowed very high incorporation efficiency for amoxicillin
      (91%) The release kinetics of amoxicillin from gellan beads followed the
      diffusion model for an inert porous matrix in the order: 0.1 N HCl > phosphate
      buffer > distilled water. Change in curing time did not significantly affect the
      release rate constant, but drug concentration, polymer concentration and
      electrolyte concentration significantly affect the release rate of amoxicillin
      from the beads. The gellan macro beads may be suitable for gastro retentive
      controlled delivery of amoxicillin.

PMID- 19863488
TI  - Development of conformational mimetics of conserved Streptococcus pyogenes
      minimal epitope as vaccine candidates.
AB  - One of the factors responsible for the poor immunogenicity of synthetic peptide
      antigens is the lack of conformational integrity. Embedding the minimal epitopes
      in helix-promoting peptide sequences has successfully enhanced the immunogenicity
      of the epitopes derived from the alpha-helical regions of the M protein of group
      A streptococci (Streptococcus pyogenes, GAS). However, the introduction of
      "foreign" peptide sequences is believed to have an unfavourable impact on the
      antigen specificity. In the current study, we employed a non-peptide approach,
      using topological carbohydrate templates, to induce helical conformation of the
      peptide antigens. Utilized together with the advances of the lipid core peptide
      system and chemoselective ligation, five GAS vaccine candidates incorporating the
      minimal epitope J14i (ASREAKKQVEKALE) were synthesized with high purity. Circular
      dichroism studies indicated that the template-assembled peptides formed alpha
      helix bundles. This atom-economic strategy also reduces the complexity and cost
      of vaccine production by simply reducing the peptide epitope size.

PMID- 19863489
TI  - Application of simplex lattice design and desirability function for the
      formulation development of mouth dissolving film of salbutamol sulphate.
AB  - The aim of the present investigation was to prepare and optimize the formulation
      of mouth dissolving film of salbutamol sulphate by applying experimental design
      technique. The films were prepared using hydroxypropyl methylcellulose, polyvinyl
      pyrrolidone and polyvinyl alcohol by solvent evaporation technique. Simplex
      lattice design and desirability function were adopted for the preparation of film
      possessing desirable and optimized characteristics. Tensile strength, elastic
      modulus, percentage strain, load at yield, and percentage drug release were
      selected as dependent variables. Regression equations and contour plots were used
      to relate the dependent and independent variables. The concept of similarity
      factor S(d) was used to prove similarity of dissolution between distilled water
      and simulated saliva (pH = 6.8). The polymers greatly influenced the mechanical
      properties and % drug release from the film. From the computed value of
      desirability function, it was determined that the film containing hydroxypropyl
      methylcellulose and polyvinyl alcohol was the best batch. The experimental design
      serves to be a useful tool for the formulation development of mouth dissolving
      film.

PMID- 19863490
TI  - Development and evaluation of in situ gel forming system for sustained delivery
      of cyclosporine.
AB  - Phase-sensitive in situ gel forming controlled release formulations of
      cyclosporine were prepared using poly (lactide-co-glycolide) and a solvent system
      consisting of various proportions of benzyl benzoate and benzyl alcohol.
      Uniformity of content of cyclosporine in the formulation and in vitro release
      samples was determined by radio immune assay (RIA). FTIR and CD spectroscopy
      ratified the conformational stability of cyclosporine in the formulation and in
      vitro release samples, respectively. Rheological properties of the formulations,
      assessed under isothermal conditions, showed dilatant behavior of all the
      formulations. In vivo studies were carried out on the optimized formulations vis
      a-vis pure cyclosporine in rats and drug levels were monitored for 13 days. Mean
      plasma concentration of cyclosporine was calculated for all the animals and
      pharmacokinetic parameters were determined using Win NonLin software. The studies
      construed better regulation of plasma drug levels with the optimized formulation
      vis-a-vis routine once-a-day administration of cyclosporine. The subcutaneous
      tissues, further subjected to histopathological examinations ascertained the
      biocompatibility of the formulation.

PMID- 19863491
TI  - In vitro and in vivo assessment of matrix type transdermal therapeutic system of
      labetalol hydrochloride.
AB  - OBJECTIVE: The aim of the investigation was to develop and evaluate matrix type
      transdermal therapeutic systems containing new polymeric combinations (Eudragit E
      PO/Eudragit RL 100 & Plasdone S 630) as polymers and Labetalol Hydrochloride
      (LBHCl) as a model drug. EXPERIMENTAL: The matrix type TTS of LBHCl were prepared
      by film casting technique. The patches were characterized for physical, in vitro
      release studies & ex-vivo permeation studies (human cadaver skin). On the basis
      of in vitro drug release and skin permeation performance, formulation A1 was
      found to be better than the other formulations and it was selected as the
      optimized formulation. The optimized patch was assessed for its pharmacokinetic,
      pharmacodynamic, skin irritation potential, and stability studies. RESULTS: The
      maximum percentage drug release & Permeation in 48 hrs were 92.43 % and 76.24 %
      respectively for optimized patch. The Korsmeyer peppas release exponent value of
      0.604 suggested release mechanism towards first order release in the optimized
      formulation. The results obtained from the in vivo characterization of the
      optimized patch showed sustained action of the developed formulation. The
      interaction studies analysis indicated no chemical interaction between the drug
      and polymers. The optimized patch was seemingly free of potentially hazardous
      skin irritation as suggested by skin irritation score of 0.915<2.00 (under Draize
      score test). The optimized formulation was found to be stable at ambient storage
      conditions. CONCLUSION: The above TTS holds promise for improved bioavailability
      and better management of hypertension on long term basis.

PMID- 19863492
TI  - Preparation and characterization of superporous hydrogels as pH-sensitive drug
      delivery system for Pantoprazole sodium.
AB  - The objective of the present study is to develop Superporous Hydrogel (SPH) and
      SPH composites (SPHC) as pH-sensitive drug delivery system for Pantaprazole
      sodium. In this investigation, Superporous hydrogels containing poly(methacrylic
      acid-co-acrylamide) with interconnected pores of several hundreds of micrometer
      were prepared using radical polymerization of methacrylic acid and acrylamide in
      the presence of N,N-methylene-bis-acrylamide as crosslinking agent. A gas blowing
      method using bicarbonate as a foaming agent was applied to introduce the porous
      structure. SPH composite polymers were made in the same way, except for using Ac
      Di-Sol as a stabilizer. The structures of the SPH and SPH composites were
      characterized by FT-IR and Scanning electron microscopy (SEM). Apparent density
      and swelling ratio studies were also carried out. The swelling properties and
      mechanical strength of SPHs were affected by the addition of the mechanical
      stabilizer, Ac-Di-Sol. Results indicated that SPH polymers have more pores and
      higher swelling ratio but less mechanical stability compared to SPH composite
      polymers, which have less pores and lower swelling ratio but a higher mechanical
      stability. With a change in pH from acidic to basic, a considerable increase in
      swelling was observed for all the formulations. Since the prepared SPH and SPHC
      swell only in the basic pH, it may be concluded that SPH and SPHC can be used as
      pH-sensitive drug delivery systems for Pantoprazole sodium.

PMID- 19863493
TI  - Gastroretentive drug delivery of metformin hydrochloride: formulation and in
      vitro evaluation using 3(2) full factorial design.
AB  - Metformin Hydrochloride (MF) is glucose lowering agent that is widely used for
      management for type II diabetes. MF is reported to be absorbed mainly in upper
      part of GIT. It is having narrow absorption window and high water solubility, and
      it would be more beneficial to retain the drug in stomach for prolonged duration
      so as to achieve maximum absorption and better bioavailability. A conventional
      oral CR formulation releases most of the drug content at the colon, which
      requires that the drug will be absorbed from the colon. The present investigation
      is aimed to develop novel gastroretentive (GR) drug delivery system, which not
      only release the drug in the absorption window but also provides controlled
      release drug profile that may result patient compliance and therapeutic success.
      Floating tablets of MF was prepared using sodium alginate, and sodium
      carboxymethylcellulose was used as a gelling agent, and release modifiers,
      respectively. Eudragit NE 30 D was used as sustained release polymer to control
      the initial burst release. Drug and excipients compatibility studies were
      monitored by thermal analysis by using differential scanning calorimeter. 32 full
      factorial design was applied to optimize the formulation. The DSC thermogram of
      drug, polymer and physical mixtures revealed that there was no known interaction
      between drug and polymers. The prepared tablets were evaluated for in vitro
      dissolution, in vitro buoyancy, percentage swelling, percentage erosion and
      similarity factors with marketed tablets. The optimization study using a 32 full
      factorial design revealed that the amount of sodium alginate and sodium
      carboxymethylcellulose had a significant effect on t50, t90, Flag and f2. Thus,
      by selecting a suitable composition of release rate modifier and gel forming
      agent, Gastro retentive system can be developed with the desired dissolution
      profile. This study indicated that the MF GR tablets prepared using sodium
      alginate and sodium carboxymethylcellulose can successfully be employed as a once
      a-day oral controlled release drug delivery system.

PMID- 19863494
TI  - Outer mitochondrial membrane localization of apoptosis-inducing factor:
      mechanistic implications for release.
AB  - Poly(ADP-ribose) polymerase-1-dependent cell death (known as parthanatos) plays a
      pivotal role in many clinically important events including ischaemia/reperfusion
      injury and glutamate excitotoxicity. A recent study by us has shown that
      uncleaved AIF (apoptosis-inducing factor), but not calpain-hydrolysed truncated
      AIF, was rapidly released from the mitochondria during parthanatos, implicating a
      second pool of AIF that might be present in brain mitochondria contributing to
      the rapid release. In the present study, a novel AIF pool is revealed in brain
      mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely
      associates with the outer mitochondrial membrane on the cytosolic side, in
      addition to its main localization in the mitochondrial intermembrane space
      attached to the inner membrane. Immunogold electron microscopic analysis of mouse
      brain further supports AIF association with the outer, as well as the inner,
      mitochondrial membrane in vivo. In line with these observations, approx. 20% of
      uncleaved AIF rapidly translocates to the nucleus and functionally causes
      neuronal death upon NMDA (N-methyl-d-aspartate) treatment. In the present study
      we show for the first time a second pool of AIF in brain mitochondria and
      demonstrate that this pool does not require cleavage and that it contributes to
      the rapid release of AIF. Moreover, these results suggest that this outer
      mitochondrial pool of AIF is sufficient to cause cell death during parthanatos.
      Interfering with the release of this outer mitochondrial pool of AIF during cell
      injury paradigms that use parthanatos hold particular promise for novel therapies
      to treat neurological disorders.

PMID- 19863495
TI  - Clinical trial: the effects of a fermented milk containing three probiotic
      bacteria in patients with irritable bowel syndrome - a randomized, double-blind,
      controlled study.
AB  - BACKGROUND: The effects of probiotic bacteria in IBS remain controversial. AIM:
      To study the effects of a probiotic product on IBS symptoms. METHODS: We
      randomized 74 IBS patients to receive 8 weeks of daily treatment with 400 mL milk
      fermented with the yoghurt bacteria and containing Lactobacillus paracasei, ssp.
      paracasei F19, Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12
      (Cultura; active) or acidified milk without these bacteria (control). The primary
      endpoint was the proportion of subjects reporting adequate relief of their IBS
      symptoms at least 50% of the weeks. IBS symptom severity, psychological symptoms
      and quality of life were assessed. RESULTS: The proportion of responders was 38%
      (14/37 patients) in the active group and 27% (10/37 patients) in the control
      group (P = 0.3). IBS symptom severity improved significantly in both groups
      during the treatment period. This change was greater in the active group during
      the first 2 weeks, but thereafter, no significant group differences were seen.
      CONCLUSIONS: We could not detect a clearly positive effect of fermented milk
      containing three probiotic bacteria on GI symptoms in IBS patients compared with
      the control treatment. However, a trend towards a more favourable effect during
      the first weeks was seen in the active group.

PMID- 19863496
TI  - Systematic review: portal vein thrombosis in cirrhosis.
AB  - BACKGROUND: As current imaging techniques in cirrhosis allow detection of
      asymptomatic portal vein thrombosis during routine ultrasonography, more patients
      with cirrhosis are diagnosed with portal vein thrombosis. Although a consensus on
      noncirrhotic extra-hepatic portal vein thrombosis has been published, no such
      consensus exists for portal vein thrombosis with cirrhosis. AIM: To perform a
      systematic review of nonmalignant portal vein thrombosis in cirrhosis in terms of
      prevalence, pathogenesis, diagnosis, clinical course and management. METHODS:
      Studies were identified by a search strategy using MEDLINE and EMBASE. RESULTS:
      Portal vein thrombosis is encountered in 10-25% of cirrhotics. In terms of
      pathophysiology, cirrhosis is no longer considered a hypocoagulable state; rather
      than a bleeding risk in cirrhosis, various clinical studies support a thrombotic
      potential. Clinical findings of portal vein thrombosis in cirrhosis vary from
      asymptomatic disease to a life-threatening condition at first presentation.
      Optimal management of portal vein thrombosis in cirrhosis is currently not
      addressed in any consensus publication. Treatment strategies most often include
      the use of anticoagulation, while thrombectomy and transjugular intrahepatic
      portosystemic shunts are considered second-line options. CONCLUSIONS: Portal vein
      thrombosis in cirrhosis has many unresolved issues, which are often the critical
      problems clinicians encounter in their everyday practice. We propose a possible
      research agenda to address these unresolved issues.

PMID- 19863499
TI  - Antinuclear antibodies associate with loss of response to antitumour necrosis
      factor-alpha therapy in psoriasis: a retrospective, observational study.
AB  - BACKGROUND: An increasing number of patients with severe psoriasis are failing to
      respond to antitumour necrosis factor (TNF)-alpha therapy (etanercept, infliximab
      and adalimumab). OBJECTIVES: We observed that many of these patients developed
      antinuclear antibodies (ANA) and antidouble-stranded DNA (anti-dsDNA) antibodies
      while on treatment prompting us to investigate whether their development is
      associated with anti-TNF treatment failure. METHODS: All patients with psoriasis
      who had received anti-TNF therapies were identified and their blood results and
      treatment histories were obtained from electronic patient records and case notes.
      RESULTS: A total of 97 patients had been treated with anti-TNF agents (60 were on
      their first agent, 22 had been on and stopped one agent, nine had been on and
      stopped two agents and six had been on and stopped all three agents). ANA
      developed in 17% of patients on their first treatment, 54% of patients who had
      failed one treatment, 78% of patients who had failed two treatments and 83% of
      patients who had failed all three treatments. Anti-dsDNA antibodies developed in
      2%, 27%, 33% and 83% of patients from the same respective groups. Significantly,
      the antibodies developed before treatment had failed with all three agents and
      their development was not related to the total time that patients had been on
      anti-TNF therapy. CONCLUSIONS: This study suggests that the development of ANA
      and anti-dsDNA antibodies on anti-TNF treatment may act as a marker of
      forthcoming treatment failure. Large-scale prospective studies are required to
      assess the importance of this observation.

PMID- 19863498
TI  - Pelvic floor disorders and quality of life in women with self-reported irritable
      bowel syndrome.
AB  - BACKGROUND: Quality of life among women with irritable bowel syndrome may be
      affected by pelvic floor disorders. AIM: To assess the association of self
      reported irritable bowel syndrome with urinary incontinence, pelvic organ
      prolapse, sexual function and quality of life. METHODS: We analysed data from the
      Reproductive Risks for Incontinence Study at Kaiser Permanente, a random
      population-based study of 2109 racially diverse women (mean age = 56).
      Multivariate analyses assessed the association of irritable bowel syndrome with
      pelvic floor disorders and quality of life. RESULTS: The prevalence of irritable
      bowel syndrome was 9.7% (n = 204). Women with irritable bowel had higher adjusted
      odds of reporting symptomatic pelvic organ prolapse (OR 2.4; 95% CI, 1.4-4.1) and
      urinary urgency (OR 1.4; 95% CI, 1.0-1.9); greater bother from pelvic organ
      prolapse (OR 4.3; 95% CI, 1.5-11.9) and faecal incontinence (OR 2.0; 95% CI, 1.3
      3.2); greater lifestyle impact from urinary incontinence (OR 2.2; 95% CI, 1.3
      3.8); and worse quality of life (P < 0.01). Women with irritable bowel reported
      more inability to relax and enjoy sexual activity (OR 1.8; 95% CI, 1.3-2.6) and
      lower ratings for sexual satisfaction (OR 1.8; 95% CI, 1.3-2.5), but no
      difference in sexual frequency, interest or ability to have an orgasm.
      CONCLUSIONS: Women with irritable bowel are more likely to report symptomatic
      pelvic organ prolapse and sexual dysfunction, and report lower quality of life.

PMID- 19863500
TI  - Topical photodynamic therapy is immunosuppressive in humans.
AB  - BACKGROUND: Visible light irradiation after application of a photosensitizer
      (topical photodynamic therapy; PDT) is increasingly used to treat nonmelanoma
      skin cancers and premalignant actinic keratoses. PDT can provide a cosmetically
      superior alternative to surgery, but carries failure rates of 10-40%. While some
      murine studies have suggested immune enhancement by PDT, others reported
      immunosuppressive effects, which may indicate impaired antitumour immunity and
      thus compromised tumour clearance. OBJECTIVES: This study aimed to determine the
      in vivo immune effects of PDT in humans. METHODS: Using healthy, Mantoux-positive
      volunteers, we irradiated discrete areas of the back with narrowband red light
      (630 nm; 37 J cm(-2)), with and without prior application of 5-aminolaevulinic
      acid (ALA) or methyl aminolaevulinate (MAL). Adjacent, untreated areas served as
      immunologically intact control sites. Delayed-type hypersensitivity responses to
      tuberculin purified protein derivative (Mantoux reactions) were then elicited in
      each of the irradiated, unirradiated and control sites, and the intensity of the
      reactions was quantitated with an erythema meter and by measurement of Mantoux
      diameter. By comparing Mantoux intensity at treated and control sites,
      immunosuppression was determined in each volunteer for each intervention.
      RESULTS: We found that both MAL-PDT and ALA-PDT significantly suppressed Mantoux
      erythema (by 30% and 50%, respectively) and diameter (41% and 38%). Red light
      alone significantly suppressed diameter (22%) but not erythema (13%).
      CONCLUSIONS: Topical PDT induced significant immune suppression, which could
      impair local antitumour immune responses and may thus contribute to treatment
      failure.

PMID- 19863501
TI  - Prednisolone vs. ciclosporin for severe adult eczema. An investigator-initiated
      double-blind placebo-controlled multicentre trial.
AB  - BACKGROUND: Patients with severe eczema frequently receive systemic
      glucocorticosteroids. The efficacy of prednisolone and other steroids, however,
      has never been evaluated appropriately. A meta-analysis indicated that
      ciclosporin is the best evaluated systemic treatment for eczema. OBJECTIVES: To
      investigate the comparative efficacy of prednisolone and ciclosporin for severe
      eczema. METHODS: In an investigator-initiated double-blind randomized multicentre
      trial, adults with severe eczema (objective SCORAD > or = 40 and Dermatology Life
      Quality Index > or = 10) were randomly allocated to receive prednisolone (initial
      dose 0.5-0.8 mg kg(-1) daily) for 2 weeks followed by placebo for 4 weeks or
      ciclosporin (2.7-4.0 mg kg(-1) daily) for 6 weeks and followed for another 12
      weeks. Concomitant treatment included a moderately potent topical steroid,
      emollients, and continuation of antihistamines. Primary endpoint was the
      proportion of patients with stable remission, i.e. > or = 50% SCORAD improvement
      under active treatment and no flare (> or = 75% of baseline SCORAD) during follow
      up. Sample size calculation indicated that 66 patients were needed to see
      clinically relevant differences between groups. Analysis was by intention-to
      treat (ClinicalTrials.gov Identifier: NCT00445081). RESULTS: Because of
      unexpectedly high numbers of withdrawals due to significant exacerbations of
      eczema (n = 15/38) an independent data monitoring and safety board proposed early
      study termination. Thirty-eight patients were randomized and analysed. Stable
      remission was achieved in one of 21 patients receiving prednisolone compared with
      six of 17 patients treated with ciclosporin (P = 0.031). CONCLUSIONS: Ciclosporin
      is significantly more efficacious than prednisolone for severe adult eczema.
      Despite its frequent use in daily practice, prednisolone is not recommended to
      induce stable remission of eczema.

PMID- 19863502
TI  - New insights into pigmentary pathways and skin cancer.
AB  - The ability of cells to respond to and to mitigate environmental stress is
      crucial for their survival. Constitutive and facultative pigmentation have
      evolved in order for human skin to contend with high levels of terrestrial
      ultraviolet radiation (UVR). When this melanin 'shield' is compromised,
      individuals are exposed to increased skin cancer risk. The purpose of this review
      is to discuss new insights into the genetic basis of phenotypic risk factors for
      skin cancer, their connection to pigmentation and tanning, the precise molecular
      connections linking UVR to the tanning response, and potential methods of
      modulating pigmentation that avoid genotoxic damage. Highly translational
      implications of this research include a scientific basis on which to counsel
      patients regarding the carcinogenicity of UVR exposure related to tanning and
      potential new tanning agents that may actually protect against skin cancer by
      circumventing the need for UVR exposure.

PMID- 19863497
TI  - Symptoms and quality of life in obese children and adolescents with non-alcoholic
      fatty liver disease.
AB  - BACKGROUND: Data on the quality of life (QOL) of children with non-alcoholic
      fatty liver disease (NAFLD) are needed to estimate the true burden of illness in
      children with NAFLD. AIM: To characterize QOL and symptoms of children with NAFLD
      and to compare QOL in children with NAFLD with that in a sample of healthy
      children. METHODS: Quality of life and symptoms were assessed in children with
      biopsy-proven NAFLD enrolled in the NASH Clinical Research Network. PedsQL scores
      were compared with scores from healthy children. For children with NAFLD, between
      group comparisons were made to test associations of demography, histological
      severity, symptoms and QOL. RESULTS: A total of 239 children (mean age 12.6
      years) were studied. Children with NAFLD had worse total (72.8 vs. 83.8, P <
      0.01), physical (77.2 vs. 87.5, P < 0.01) and psychosocial health (70.4 vs. 81.9,
      P < 0.01) scores compared with healthy children. QOL scores did not significantly
      differ by histological severity of NAFLD. Fatigue, trouble sleeping and sadness
      accounted for almost half of the variance in QOL scores. Impaired QOL was present
      in 39% of children with NAFLD. CONCLUSIONS: Children with NAFLD have a decrement
      in QOL. Symptoms were a major determinant of this impairment. Interventions are
      needed to restore and optimize QOL in children with NAFLD.

PMID- 19863503
TI  - Association of human papillomavirus 7 with warts in toe webs.
AB  - BACKGROUND: There have been no studies on the prevalence of types of human
      papillomavirus (HPV) in cutaneous warts that focus on warts in toe webs (WTW).
      There is no documented association between HPV 7 and WTW. OBJECTIVES: To explore
      the clinical and histopathological features of WTW, and the distribution of HPV
      genotypes in patients with WTW. METHODS: The study group consisted of 20 patients
      with WTW; 31 patients with typical verruca vulgaris (VV) were enrolled as the
      disease control group, and 53 patients with tinea pedis and 48 healthy volunteers
      were enrolled as the disease-negative control group. Tissue specimens were
      analysed for clinical and histological features and distribution of HPV
      genotypes. Polymerase chain reaction (PCR)-based direct sequencing, TA cloning
      and type-specific PCR (TS-PCR) were performed in the WTW and VV groups.
      Interdigital scale specimens from patients with tinea pedis and from healthy
      volunteers were analysed for HPV DNA by nested PCR and TS-PCR (HPV 7). RESULTS:
      All the patients with WTW were male and nearly all were immunocompetent; their
      mean age was 41 +/- 10 years. The lesions presented mainly as soft, friable and
      vegetating clusters. HPV 7 was the predominant genotype in WTW with a frequency
      of 80% (16/20). Fourteen specimens were taken for histopathological examination.
      The most frequent histological results (seven out of 14) revealed characteristics
      of HPV 7 infections such as heavily stained cells containing medium-sized
      keratohyaline granules and a pronounced hyperkeratosis with parakeratosis. TA
      cloning showed that the sequence shared 90% or more homology with the HPV
      genotype in direct sequencing. No HPV 7 DNA was found in the scales taken from
      toe webs without warts. CONCLUSIONS: This is the first study evaluating the
      prevalence of HPV types in WTW and the first report of the association between
      HPV 7 and specific subgroups of patients with warts.

PMID- 19863504
TI  - Unique skin changes in a case of Albright hereditary osteodystrophy caused by a
      rare GNAS1 mutation.
AB  - Albright hereditary osteodystrophy (AHO) is a syndrome of short stature, obesity,
      brachydactyly and subcutaneous calcifications with pseudohypoparathyroidism (PHP;
      leading to hypocalcaemia, hyperphosphataemia and elevated levels of parathyroid
      hormone, PTH). It was first described over 60 years ago. Since then, much has
      been learned about the aetiology of AHO which has been shown to be caused by
      heterozygous loss-of-function mutations within the GNAS1 gene. GNAS1 is subject
      to imprinting leading to phenotypic heterogeneity within kindreds with one
      mutation. Patients with AHO often present with symptoms of hypocalcaemia and/or
      with subcutaneous calcifications. The latter is thought to be the typical skin
      abnormality in AHO. We describe a family with AHO and hormone resistance (PHP
      type Ia) resulting from a rare mutation in GNAS1. The proband presented with
      small subcutaneous calcifications in the helix of the right ear and concentrated
      in a sharply demarcated zone of subcutaneous and dermal hypoplasia. This
      abnormality has so far not been described in patients with AHO. We speculate on
      the mechanism of dermal hypoplasia and resistance to PTH and suggest that
      subcutanous or dermal hypoplasia might be another feature which can be present in
      patients with AHO.

PMID- 19863505
TI  - Association analysis of filaggrin gene mutations and atopic dermatitis in
      Northern China.

PMID- 19863506
TI  - Genotype-phenotype correlations with TGM1: clustering of mutations in the bathing
      suit ichthyosis and self-healing collodion baby variants of lamellar ichthyosis.

PMID- 19863507
TI  - Rhabdomyomatous mesenchymal hamartoma resembling scleroderma 'en coup de sabre':
      a case report and literature review.

PMID- 19863508
TI  - The 'crossover' tip-stitch in O-T flap repair.

PMID- 19863509
TI  - Keratin 16 expression in epidermal melanocytes.

PMID- 19863511
TI  - Facilitating closure of surgical defects on the lower legs with a simple knee
      bend.

PMID- 19863510
TI  - Modification of the cutaneous dermatomyositis disease area and severity index, an
      outcome instrument.
AB  - BACKGROUND: Validated outcome measures in dermatology help standardize and
      improve patient care. A scoring system of skin disease severity in
      dermatomyositis known as the Cutaneous Dermatomyositis Disease Area and Severity
      Index (CDASI) has been developed. OBJECTIVES: To simplify and improve the tool
      for clinical research and care, we modified the CDASI and validated the new
      version, v2. METHODS: The original CDASI has four activity and two damage
      measures. The modified CDASI has three activity and two damage measures. The skin
      disease of 20 patients with dermatomyositis was evaluated by the same
      dermatologist using both the original and the modified CDASI. Global validation
      measures were implemented to assess overall skin disease state, skin disease
      activity and skin damage. Spearman's rho (r(sp)), adjusted for multiple
      observations on subjects, was used to determine the relationship between the two
      versions of the CDASI and their correlation with the physician global measures
      (PGMs). RESULTS: The total score and activity and damage subscores of the
      original and the modified CDASI correlated perfectly with each other (r(sp) =
      0.99, 1.00, 1.00). The PGM-overall skin scale correlated with the total scores
      (r(sp) = 0.72, r(sp) = 0.76) and activity subscores (r(sp) = 0.68, r(sp) = 0.63)
      but not with the damage subscores (r(sp) = 0.14, r(sp) = 0.15) of the original
      and the modified CDASI, respectively. However, the PGM-activity and PGM-damage
      scales correlated with the activity (r(sp) = 0.76, r(sp) = 0.75) and damage
      subscores (r(sp) = 0.90, r(sp) = 0.90), respectively, of the original and the
      modified CDASI. CONCLUSIONS: The modified CDASI is perfectly correlated with the
      original CDASI. It has equally good concurrent validity with the PGM-overall skin
      and PGM-activity scales. The CDASI subscores have equally good concurrent
      validity with the PGM-activity and PGM-damage scales. We suggest that PGMs of
      skin disease activity and damage should be assessed separately for greater
      specificity. The modified CDASI is a refined and equally as useful outcome
      measure.

PMID- 19863512
TI  - Placental hypoxia and neonatal haemangioma: clinical and histological
      observations.

PMID- 19863513
TI  - Skin cancer: preventive photodynamic therapy in patients with face and scalp
      cancerization. A randomized placebo-controlled study.
AB  - Background Patients with a previous medical history of nonmelanoma skin cancers
      (NMSCs) often develop multiple or recurrent malignant lesions around the site of
      the primary tumour. This finding led to the field cancerization theory, which
      suggests that the entire epithelial surface of the regional skin has an increased
      risk for the development of malignant lesions. Management of field change is
      challenging, taking into account the high impact of NMSCs on public health and
      healthcare costs. Objectives We sought to investigate whether field-photodynamic
      therapy (PDT) of extreme photodamaged skin would prevent new NMSCs, in comparison
      with a control area receiving placebo-PDT, in patients with clinical and
      histological signs of field cancerization. Methods Forty-five patients,
      previously diagnosed as having NMSCs of the face or scalp, with actinic keratoses
      symmetrically distributed over the same regions, were randomized for field
      treatment with 20% aminolaevulinic acid (ALA)-PDT on one side and placebo-PDT on
      the other. During the next 12-month period of follow up, patients were clinically
      evaluated for new NMSCs. Results A significant delay in the mean time of
      appearance and a reduction in the total number of new lesions were observed in
      the field-PDT protocol, when compared with the control. Conclusions The results
      obtained showed that field therapy with ALA-PDT confers a significant preventive
      potential against the formation of new NMSCs in patients with field changes.

PMID- 19863514
TI  - Intradermal injections of polyarginine-containing immunogenic antigens
      preferentially elicit Tc1 and Th1 activation and antitumour immunity.
AB  - Background We previously have shown that nona-arginine protein transduction
      domain (R9-PTD) induced efficient protein-antigen (Ag) transduction of dendritic
      cells (DCs) in vitro, resulting in the efficient induction of strong Ag-specific
      immune responses mediated by CD8+ and CD4+ T cells and in superior antitumour
      effects in vivo in cancer-bearing mice. Objectives The Ag-specific immune
      responses caused by intradermal (i.d.) injections of R9-PTD-containing protein
      Ags without DC preparation were investigated. We also investigated the antitumour
      effects by intratumoral (i.t.) injections of rR9-containing protein Ags. Methods
      Synthesized SIINFEKL peptide, or recombinant ovalbumin fusion proteins (rOVA, rR9
      OVA), were directly injected into abdominal skin in naive C57BL/6 mice. OVA
      specific cytotoxic T lymphocyte (CTL) activity, serum IgG titre and cytokine
      profiles were investigated. Histopathological analyses were also performed. In a
      cancer vaccination model, EG.7 (OVA-cDNA transfectants thymoma) cells were
      inoculated intradermally in C57BL/6 mice, and the antitumour effects were
      evaluated by i.t. injections of rR9-OVA in a treatment setting. Results i.d.
      injections of rR9-OVA into naive C57BL/6 mice elicited OVA-specific CTLs and
      produced IgG2-dominant immunoglobulin. The i.d. injections of rR9-OVA also
      induced inflammatory cell infiltrates containing neutrophils, monocytes and
      lymphocytes, as well as production of inflammatory cytokines such as interferon
      (IFN)-gamma, interleukin-2 and IFN-inducible protein 10, with presenting SIINFEKL
      epitopes on major histocompatibility complex (MHC) class I molecules at the
      injection area. i.t. injections of rR9-OVA into EG.7 tumour mass significantly
      suppressed tumour growth, and these effects were completely abrogated by the
      depletion of CD8+ T cells. These antitumour effects were superior to those
      elicited by i.t. injections of rR9-OVA-treated DCs. Conclusions i.d. injections
      of rR9-containing immunogenic Ag without adjuvants simultaneously induce dual
      immunological effects: the induction of Tc1- and Th1-dominant immune responses,
      and the induction of inflammatory and CTL-mediated immune responses at the
      injection area by expressing Ag epitopes on MHC class I molecules as targets.
      This simple vaccination approach with R9-PTD-containing fusion proteins might be
      useful as prophylactic immunotherapy for cancer or infectious diseases.

PMID- 19863515
TI  - Repeated low-dose skin exposure is an effective sensitizing stimulus, a factor to
      be taken into account in predicting sensitization risk.
AB  - BACKGROUND: Contact sensitization by ingredients in personal products is an
      important clinical problem. It is not clear how sensitization is induced by the
      generally low concentrations at which they occur but it might be the result of
      repeated exposure. OBJECTIVES: To compare the strength of contact sensitization
      induced by a single exposure to 2,4-dinitrochlorobenzene (DNCB) (60 microg cm(
      2)) or three repeated exposures to a subsensitizing dose (10 microg cm(-2)).
      METHODS: Two groups (n = 10) of healthy adult volunteers were randomized to
      receive either a single patch of DNCB 60 microg cm(-2) or three once-weekly
      applications to the same site of 10 microg cm(-2) DCNB. Four weeks after the last
      application, sensitization was quantified by measurement of responses (skinfold
      thickness) to a graded series of four challenge doses. RESULTS: All the
      volunteers were sensitized and the strength of the responses was virtually
      identical between the groups. CONCLUSIONS: The same degree of sensitization was
      induced by three exposures to DNCB 10 microg cm(-2) as by one exposure to 60
      microg cm(-2) of DNCB. Thus repeated exposure to low doses of contact sensitizers
      may increase the sensitizing potency. This must be taken into account in future
      risk assessments.

PMID- 19863516
TI  - Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of
      bladder cancer.
AB  - OBJECTIVES: To determine whether or not an improved hygiene can lessen the
      incidence of symptomatic urinary tract infections (UTIs) in patients treated by
      cystectomy for urinary bladder cancer. PATIENTS AND METHODS: We attempted to
      contact during their follow-up all men and women aged 30-80 years who had
      undergone cystectomy and urinary diversion at seven Swedish hospitals. During a
      qualitative phase we identified hygienic measures and included them in a study
      specific questionnaire. The patients completed the questionnaire at home. Outcome
      variables were dichotomized and the results presented as relative risks (RR) with
      95% confidence interval. RESULTS: We received the questionnaire from 452 (92%) of
      491 identified patients. The proportion of patients who had a symptomatic UTI in
      the previous year was 22% for orthotopic neobladder and cutaneous continent
      reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1
      (0.5-2.5) for 'never washing hands' before handling with catheters or ostomy
      material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a
      symptomatic UTI. CONCLUSIONS: We could not confirm lack of hygiene measures as a
      cause of UTI for men and women who had a cystectomy with urinary diversion.
      Patients with diabetes mellitus have a greater risk of contracting a UTI.

PMID- 19863517
TI  - A double-blind placebo-controlled study of the efficacy and safety of
      pentoxifylline in early chronic Peyronie's disease.
AB  - OBJECTIVE: To analyse the safety and efficacy of pentoxifylline sustained-release
      (PTX-SR) treatment in patients with early chronic Peyronie's disease (PD).
      PATIENTS AND METHODS: In all, 228 patients with a mean (sd) age of 51 (9) years
      who had early chronic PD were randomized to receive 400 mg PTX-SR (Apo
      Pentoxifylline, Apotex Inc., Toronto, Canada) twice daily (group 1, 114) or
      similar regimen of placebo (group 2, 114) for 6 months. A medical history was
      taken and the men had a complete physical examination. The following variables
      were assessed before and after therapy: penile curvature and penile artery
      spectral traces (end-diastolic velocity, EDV, peak systolic velocity, PSV, and
      resistivity index, RI, of the right and left cavernous arteries assessed with
      dynamic penile duplex ultrasonography), plaque characteristics (assessed by
      penile X-ray and penile ultrasonography), pain (assessed by visual analogue
      scale), erectile function (assessed by the International Index of Erectile
      Function, IIEF questionnaire), treatment satisfaction (assessed by Erectile
      Dysfunction Inventory of Treatment Satisfaction questionnaire), and side-effects.
      Patient perception of penile curvature and plaque size, and mean weekly
      intercourse attempts were also assessed. RESULTS: Overall, 36.9% of patients who
      received PTX-SR reported a positive response, vs only 4.5% in the placebo group.
      Of patients in PTX-SR group, 12 (11%) had disease progression, vs 46 (42%) in
      placebo group (P = 0.01). Improvement in penile curvature (P = 0.01), and plaque
      volume (P = 0.001) was significantly greater in patients treated with PTX-SR than
      placebo. The increase in IIEF total score was significantly higher in the PTX-SR
      group (P = 0.02). Mean PSV changes after therapy compared to baseline were
      statistically significant between PTX-SR (right, +11.4%, left, +11.7%) and
      placebo-treated (+0.2% and -4.2%, respectively) patients (both P = 0.04).
      CONCLUSIONS: PTX-R was moderately effective in reducing penile curvature and
      plaque volume in patients with early chronic PD. Further studies with different
      treatment regimens are needed to better elucidate the beneficial effects of PTX
      SR in PD.

PMID- 19863518
TI  - Genetic and environmental effects on the continuity of ejaculatory dysfunction.
AB  - OBJECTIVES: To investigate temporal continuity in ejaculatory dysfunction by
      comparing self-reported experiences of premature ejaculation (PE) at first
      intercourse with self-reported PE and delayed ejaculation at present, and to
      clarify whether and to what extent genetic or environmental factors affect
      continuity in ejaculatory dysfunction, as previous studies indicate moderate
      heritability for PE at first intercourse. SUBJECTS AND METHODS: The study
      comprised retrospective self-reported data on ejaculatory performance at first
      sexual intercourse and a concurrent self-report of the same at the time of data
      collection in a population-based sample of 2633 Finnish twins and their siblings
      aged 18-48 years (mean 26.63, sd 4.68). The continuity of ejaculatory function
      was assessed by correlation and multiple regression. Reasons for continuity were
      separated into genetic and environmental sources using twin-model fitting.
      RESULTS: Ejaculatory function, particularly PE, was stable over time. Genetic
      effects accounted for approximately 30% of the variance in PE both at first
      intercourse and when measured at data collection. Unshared environmental effects
      accounted for most of the variance ( approximately 70%). Genetic effects were
      almost identical between the sample occasions, but there was a substantial
      discrepancy between unshared environmental effects affecting PE at first
      intercourse and unshared environmental effects affecting PE later in life. Age
      effects were generally negligible. Data were self-reported and retrospective, and
      thus vulnerable to response bias. CONCLUSIONS: Ejaculatory dysfunction seems to
      be temporally stable both in the short and long term. Genes that contribute to
      the variance in PE at first intercourse are similar to those that contribute to
      the variance in PE later in life, whereas there are, in this regard, substantial
      differences in the unshared environmental factors that are a cause of PE.

PMID- 19863519
TI  - The effect of nitric oxide on adherence of P-fimbriated uropathogenic Escherichia
      coli to human renal epithelial cells.
AB  - OBJECTIVES: To examine the effect of nitric oxide (NO), an endogenous component
      of the host defence in urinary tract infection, on the adherence of P-fimbriated
      uropathogenic Escherichia coli (UPEC) to human renal epithelial cells. MATERIALS
      AND METHODS: Two wild-type UPEC strains (AD110 and IA2) and the P-fimbriated
      recombinant strain HB101pPIL-75 were used. Bacteria were allowed to adhere to the
      human renal epithelial cell line A498 and attachment was evaluated in the absence
      or presence of the NO donor DETA/NONOate (1 mm). Total RNA was extracted from NO
      exposed bacteria in static urine cultures, followed by semi-quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) analysis of the papG gene that
      encodes the P-fimbriae adhesin PapG. RESULTS: Bacterial adherence to A498 cells
      was fimbriae-dependent and the ability to agglutinate human P(1) positive
      erythrocytes confirmed that the used strains were P-fimbriated. UPEC strains
      AD110 and IA2 attached by a mean of 8 bacteria/cell and 20 bacteria/cell,
      respectively. In the presence of DETA/NONOate, the attachment of AD110 and IA2 to
      A498 cells was significantly reduced by a mean (sem) of 34 (3.9)% and 45 (14)%,
      respectively. The expression of papG was decreased after DETA/NONOate exposure as
      shown by semiquantitative RT-PCR. CONCLUSION: NO disrupted functional adhesion of
      P-fimbriated UPEC to kidney epithelial cells, suggesting that NO-production from
      epithelial cells in the urinary tract may limit bacterial colonization at the
      mucosal surface. The reduced adherence may involve transcriptional effects of NO
      on papG expression, but further studies are needed to establish the underlying
      mechanisms.

PMID- 19863520
TI  - Development and validation of an Arabic version of the International Prostate
      Symptom Score.
AB  - OBJECTIVE: To develop and validate an Arabic version of the International
      Prostate Symptom Score (IPSS). PATIENTS, SUBJECTS AND METHODS: An Arabic version
      of the IPSS (IPSS-Arb) was developed through a series of translations and
      modifications which involved the authors, urology and non-urology medical and
      nursing staff. The validity and reliability were assessed in 76 patients with
      urinary symptoms due to benign prostatic hyperplasia (BPH) and in 63 control
      subjects without BPH; 25 patients had transurethral resection of prostate (TURP)
      whereas the remaining 51 patients were treated with terazosin. The reliability of
      the IPSS-Arb was assessed by determining the internal consistency (Cronbach's
      alpha coefficient) and by assessing the test-retest reliability (intraclass
      correlation coefficient, ICC). Construct validity was assessed by determining the
      correlation between the IPSS-Arb scores and the quality-of-life question (QoL
      Arb), and by determining the ability of the IPSS-Arb to discriminate between the
      patients and controls by calculating the area under the receiver operating
      characteristic (ROC) curve. RESULTS: The Cronbach's alpha coefficient (internal
      consistency) for the IPSS-Arb was 0.85, and 0.78-0.88 for the individual items.
      The test-retest reliability (ICC) was 0.88 (P < 0.001). In addition, the IPSS-Arb
      had a high correlation with the QoL-Arb (Spearman rank correlation coefficient
      0.82, P = 0.01). The mean (sem, 95% confidence interval) area under the ROC curve
      for the IPSS-Arb was 0.93 (0.09, 0.89-0.97), whereas the area for its individual
      questions was 0.79-0.90. The IPSS-Arb also showed a high sensitivity to change.
      The mean (sd) IPSS-Arb scores before and after TURP were 23.1 (6.4) and 6.9
      (1.8), respectively (P < 0.001); in the terazosin group, the scores were 12.6
      (7.4) and 8.2 (4.0), respectively (P < 0.001). CONCLUSIONS: The IPSS-Arb was
      shown to be a reliable and valid instrument for patients with BPH. We recommend
      using it for patient assessment and follow-up, and as a research tool in Arabic
      speaking patients both in the Middle East and worldwide. In addition, this study
      provided another proof of the wide suitability of the IPSS among various nations
      worldwide.

PMID- 19863521
TI  - Radical prostatectomy as initial monotherapy for patients with pathologically
      confirmed high-grade prostate cancer.
AB  - OBJECTIVE: To report the long-term outcome of high-grade prostate cancer treated
      with radical prostatectomy (RP) as initial monotherapy, analyse the effect of
      clinical and pathological variables on survival, and report cancer-related
      symptoms. PATIENTS AND METHODS: A retrospective chart review was conducted to
      identify patients with Gleason 8-10 prostate cancer found on pathological review
      in men undergoing RP as initial therapy for clinically localized disease between
      1988 and 2005. Kaplan-Meier analysis was used to calculate event-free survival.
      Univariable and multivariable analyses were used to assess the effects of
      clinical and pathological variables on prostate-specific antigen (PSA)
      recurrence. RESULTS: After excluding 20 patients, 119 were identified with
      pathologically confirmed high-grade cancers at the time of RP. The overall median
      (interquartile range) follow-up was 73 (41-113) months. Twenty-four (20%)
      patients had organ-confined cancer, 60 (50%) had specimen-confined cancer, and 14
      (12%) had nodal metastasis. Kaplan-Meier analysis showed overall survival rates
      at 5 and 10 years, respectively, of 90% and 75%, cancer-specific survival of 92%
      and 82%, and a PSA recurrence-free follow-up at 5 years of 31%. Using univariable
      analysis, preoperative PSA level, pathological Gleason score, pathological stage,
      surgical margin status and tumour volume were found to significantly affect the
      PSA recurrence-free follow-up. No variables were significant on multivariable
      analysis. Cancer-related symptoms were reported by only 14 patients, with a
      median time from surgery to first symptom of 43 months. CONCLUSION: High-grade
      prostate cancer can be treated with RP as initial monotherapy with an acceptable
      10-year cancer-specific survival (82%). The PSA recurrence-free follow-up is poor
      (31% at 5 years). However, few patients progress to symptomatic recurrence after
      PSA relapse within the first 5 years.

PMID- 19863522
TI  - The 12-year symptomatic outcome of transurethral resection of the prostate for
      patients with lower urinary tract symptoms suggestive of benign prostatic
      obstruction compared to the urodynamic findings before surgery.
AB  - OBJECTIVE: To investigate whether bladder outlet obstruction (BOO), detrusor
      underactivity (DUA) and detrusor overactivity (DO) affect the long-term outcome
      of transurethral resection of the prostate (TURP) for patients having lower
      urinary tract symptoms suggestive of benign prostatic obstruction. PATIENTS AND
      METHODS: Of 92 patients who had TURP after a urodynamic study between 1995 and
      1997, 43 (47%) were alive at the time of the survey in February 2008. Nine
      patients were excluded because of prostate cancer, neurological diseases and the
      impossibility of symptomatic examination. The International Prostate Symptom
      Score (IPSS) and quality-of-life (QoL) index were determined at baseline, 3
      months, 3, 7 and 12 years after surgery for 34 patients. RESULTS: Although the
      improved IPSS and QoL index at 3 months gradually deteriorated with time,
      patients at 12 years were still significantly better than those at baseline. The
      IPSS in patients without BOO deteriorated faster than in those with it, whereas
      neither DUA nor DO influenced the slope of change in IPSS. Regardless of the
      preoperative urodynamic findings, the QoL index remained improved for 12 years.
      Two-thirds of patients with DUA but not BOO were satisfied with their urinary
      condition at 12 years. CONCLUSION: The symptomatic improvement provided by TURP
      lasts for >10 years, although there is a gradual deterioration with time. The QoL
      index remained improved for 12 years regardless of the preoperative urodynamic
      findings.

PMID- 19863523
TI  - The relationship between age at time of surgery and risk of biochemical failure
      after radical prostatectomy.
AB  - OBJECTIVES: To evaluate the effects of age at radical prostatectomy (RP) on
      recurrence-free survival (RFS) in patients with prostate cancer stratified by
      established preoperative risk factors (such as prostate-specific antigen (PSA)
      level, Gleason score, and tumour stage), as increasing age has been associated
      with more indolent behaviour in some cancers. PATIENTS AND METHODS: A
      retrospective analysis of men treated with RP from 1988 to 2008 was conducted.
      Patients were divided into two groups by age at the time of RP, and RFS rates
      were analysed using Kaplan-Meier survival curves. The subgroups were stratified
      by preoperative PSA level, biopsy Gleason score, and clinical stage; multivariate
      analyses with Cox proportional hazards models were used to identify independent
      predictors of recurrence. Recurrence was defined as a single PSA level of > or
      =0.2 ng/mL at least 28 days after RP. RESULTS: In all, 1984 patients met
      inclusion criteria and were divided into groups 1 (1325 men aged 40-64 years) and
      2 (659 men aged > or =65 years). The 5-year RFS rates were 80.6% (confidence
      interval, CI 78.0-82.9%) and 75.6% (CI 71.5-79.1%) for groups 1 and 2,
      respectively. In the univariate model, advanced age was significantly associated
      with an increased overall risk of recurrence (hazard ratio, HR 1.30, P = 0.012).
      However, in multivariate analyses accounting for PSA level, Gleason score, and
      clinical stage, age was not an independent predictor of recurrence (HR 1.04, P =
      0.76). CONCLUSION: Older patients who undergo RP appear to have an increased risk
      of recurrence. However, age is not an independent predictor of recurrence when
      accounting for PSA level, grade, and stage.

PMID- 19863524
TI  - The effect of Gleason score on the predictive value of prostate-specific antigen
      doubling time.
AB  - OBJECTIVE: To evaluate the influence of the pathological Gleason score on the
      predictive value of the prostate-specific antigen (PSA) doubling time (DT), as
      this variable predicts a patient's risk of disease progression both before and
      after definitive therapy for prostate cancer, and there is an inverse correlation
      between the Gleason score and PSA production. PATIENTS AND METHODS: We evaluated
      all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not
      receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had
      multiple PSA values available before RP, and 1323 who had biochemical recurrence
      after RP and had at least two PSA values available before starting secondary
      therapy. Systemic progression and cancer-specific survival (CSS) rates were
      estimated using the Kaplan-Meier method and Cox proportional hazard regression
      models. RESULTS: A PSA DT of <18 vs >18 months predicted a lower 10-year systemic
      progression-free survival for patients with tumours having a pathological Gleason
      score of <7 (98% vs 99%, P = 0.005), 7 (82% vs 91%, P = 0.003) and 8-10 (57% vs
      73%, P = 0.042). A PSA DT after RP of <12 months was significantly associated
      with a lower 10-year systemic progression-free survival for patients with tumours
      having a Gleason score of <7 (77% vs 94%, P < 0.001) and 7 (61% vs 86%, P <
      0.001), but not 8-10 (61% vs 75%, P = 0.11). The ability of PSA DT before and
      after RP to predict systemic progression and CSS decreased with increasing
      Gleason score. CONCLUSIONS: The PSA DT remains associated with outcome both
      before and after RP across increasing pathological Gleason scores, although the
      predictive ability of PSA DT is diminished in Gleason 8-10 cancers.

PMID- 19863525
TI  - Angiogenesis inhibitor therapies for metastatic renal cell carcinoma:
      effectiveness, safety and treatment patterns in clinical practice-based on
      medical chart review.
AB  - OBJECTIVE: To assess the effectiveness, safety, and treatment patterns of anti
      angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical
      practice settings. PATIENTS AND METHODS: We retrospectively reviewed the medical
      records in two tertiary oncology centres in the USA for all patients treated
      while off clinical trials from April 2003 to June 2008 who met the entry criteria
      and received one or more prescriptions for sunitinib or sorafenib, or one or more
      intravenous administrations of bevacizumab (off-label) as first-line anti
      angiogenic treatment. The objective response rate (ORR) reviewed by independent
      physicians, adverse events (AEs), and treatment modifications were assessed.
      RESULTS: Among 144 patients receiving sunitinib (57), sorafenib (62) and
      bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and
      the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with
      metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for
      sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%),
      fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51
      (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab,
      respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%)
      discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35%
      and 0% had a dose reduction. CONCLUSIONS: Currently available anti-angiogenic
      agents had considerable effectiveness in clinical practice. However, the response
      rates appeared to be low in certain subgroups, but sample sizes were small.
      Patients had significant rates of AEs, many of which led to treatment
      modifications. The findings from this retrospective study suggest that there is a
      need for better-tolerated therapies for mRCC.

PMID- 19863527
TI  - Regional variations in small intestinal submucosa evoke differences in
      inflammation with subsequent impact on tissue regeneration in the rat bladder
      augmentation model.
AB  - OBJECTIVE: To examine the histological differences in the inflammatory response
      and regenerative outcomes of distal vs proximal porcine small intestinal
      submucosa (SIS) grafts in the rat bladder, as SIS from distal small intestine
      yields reliable and reproducible bladder regeneration, while SIS from proximal
      portions of small intestine does not provide similar results. MATERIALS AND
      METHODS: In all, 30 Sprague-Dawley rats underwent hemi-cystectomy followed by
      anastomosis of a bladder patch of SIS prepared from either distal or proximal
      small intestine. After bladder harvest, immunohistochemistry was used to quantify
      mast cells, eosinophils, macrophages, and neutrophils (PMNs). Total cell count
      per unit area was compared across the time course in univariate and logistic
      regression modelling. RESULTS: There were more eosinophils and mast cells in
      proximal SIS grafts, while there were more macrophages and PMNs in distal SIS
      grafts (all P < 0.05). Trichrome analysis showed increased collagen deposition in
      proximal SIS grafts and little smooth muscle regeneration. There was also
      significant graft contracture in proximal SIS grafts compared with distal SIS
      grafts (P < 0.05). CONCLUSIONS: We conclude that the location of SIS origin may
      evoke different inflammatory responses, which results in altered bladder tissue
      regeneration.

PMID- 19863528
TI  - Contrast-enhanced colour Doppler-targeted vs a 10-core systematic repeat biopsy
      strategy in patients with previous high-grade prostatic intraepithelial
      neoplasia.
AB  - OBJECTIVE: To compare the results of contrast-enhanced colour Doppler (CECD)
      targeted prostate biopsy with a systematic 10-core grey-scale biopsy scheme in
      patients initially diagnosed with high-grade prostatic intraepithelial neoplasia
      (HGPIN), as although HGPIN is thought to be a precursor to invasive
      adenocarcinoma, its diagnosis is no longer considered an indication for repeat
      prostate biopsy and patients should be followed by prostate-specific antigen
      levels and a digital rectal examination. PATIENTS AND METHODS: In all, 104
      patients (aged 45-78 years) diagnosed with HGPIN on initial prostate needle
      biopsy were referred for a repeat biopsy within 6 months. Two independent
      examiners evaluated each patient; one used CECD-targeted biopsy (up to five
      cores) into hypervascular regions in the peripheral zone only, and subsequently
      the second took a systematic 10-core grey-scale biopsy. Cancer detection rates of
      both techniques were compared. RESULTS: Overall, 26 of the 104 men (25%) had
      prostate cancer in the repeated biopsy. Using the CECD technique cancer was
      detected in 21% (22 of 104). The positive re-biopsy rate using the systematic
      technique was 9.6% (10 of 104; P < 0.001). The total incidence of HGPIN with no
      evidence of tumour on re-biopsy was 8.7% (nine of 104). The Gleason score in all
      22 cancers detected with the CECD technique varied between 6 and 8. The
      systematic technique detected cancers with Gleason scores of 6 or 7. There were
      no adverse events or complications. CONCLUSION: CECD increased the detection rate
      of prostate cancer, and using fewer biopsy cores than the systematic biopsy
      technique in patients previously diagnosed with HGPIN.

PMID- 19863529
TI  - The prognostic significance of bladder neck invasion in prostate cancer: is
      microscopic involvement truly a T4 disease?
AB  - Since the widespread of prostate-specific antigen-based screening, prostate
      cancer at clinical stage T4 has become rare. Most bladder invasion is actually
      detected on radical prostatectomy specimens as a microscopic bladder neck
      involvement (BNI). The 2002 Tumour-Node-Metastasis (TNM) classification system
      classified prostate cancer with BNI within a unified pT4 category and rendered it
      equivalent to invasion into the pelvic wall musculature or external sphincter;
      this decision is controversial. Various series have assessed the clinical
      relevance and the effect of BNI on prognosis. This evidence-based review provides
      evidence that BNI should be assigned within the subset of pT3 stage, and that
      further improvement of the actual TNM staging system should be considered.
      However, BNI remains strongly associated with adverse pathology and should be
      regarded as a factor that worsens the prognosis of the underlying tumour stage.

PMID- 19863530
TI  - Single-port, single-operator-light endoscopic robot-assisted laparoscopic
      urology: pilot study in a pig model.
AB  - OBJECTIVES: To present our initial operative experience in which single-port
      light endoscopic robot-assisted reconstructive and extirpative urological surgery
      was performed by one surgeon, using a pig model. MATERIALS AND METHODS: This
      pilot study was conducted in male farm pigs to determine the feasibility and
      safety of single-port, single-surgeon urological surgery. All pigs had a general
      anaesthetic and were placed in the flank position. A 2-cm umbilical incision was
      made, through which a single port was placed and pneumoperitoneum obtained. An
      operative laparoscope was introduced and securely held using a novel low-profile
      robot under foot and/or voice control. Using articulating instruments, each pig
      had bilateral reconstructive and extirpative renal surgery. Salient
      intraoperative and postmortem data were recorded. Results were analysed
      statistically to determine if outcomes improved with surgeon experience. RESULTS:
      Five male farm pigs underwent bilateral partial nephrectomy and bilateral
      pyeloplasty before a completion bilateral radical nephrectomy. There were no
      intraoperative complications and there was no need for additional ports to be
      placed. The mean (range) operative duration for partial nephrectomy, pyeloplasty,
      and nephrectomy were 120 (100-150), 110 (95-130) and 20 (15-30) min,
      respectively. The mean (range) estimated blood loss for all procedures was 240
      (200-280) mL. The preparation time decreased with increasing number of cases (P =
      0.002). CONCLUSIONS: The combination of a single-port, a robotic endoscope holder
      and articulated instruments operated by one surgeon is feasible. With a single
      port access, the robot allows more room to the surgeon than an assistant.

PMID- 19863531
TI  - Detection rate and factors predictive the presence of prostate cancer in patients
      undergoing ultrasonography-guided transperineal saturation biopsies of the
      prostate.
AB  - OBJECTIVES: To assess the prostate cancer detection rate and predictive factors
      for prostate cancer after transrectal ultrasonography (TRUS)-guided transperineal
      saturation re-biopsies of the prostate, using a 24-core scheme. PATIENTS AND
      METHODS: We evaluated 143 consecutive patients undergoing TRUS-guided
      transperineal saturation re-biopsy of the prostate using a 24-core scheme. The
      inclusion criteria were a previous negative biopsy and a prostate-specific
      antigen (PSA) level of > or =10.0 ng/mL, or of 4.0-10.0 ng/mL with a free/total
      ratio of <20% or an abnormal digital rectal examination or previous high-grade
      prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar
      proliferation (ASAP). RESULTS: The mean (sd) age of the patients was 66.5 (6.1)
      years and the median (interquartile range) PSA level was 9.0 (6.1-12.8) ng/mL.
      The number of previous biopsies was one in 59% of patients, two in 26% and three
      or more in 15%. We detected prostate cancer in 26%, ASAP in 5.6% and HGPIN in
      2.1%. The cancer detection rate was 47%, 25.5% and 14% for prostate volumes of
      <40, 40-60 and > or =60 mL, respectively (P = 0.002). On a multivariate analysis
      the total prostate volume (40-60 vs <40 mL, hazard ratio 5.683; >60 vs <40 mL,
      hazard ratio 6.965; P = 0.01) was the only significant predictor of prostate
      cancer at saturation biopsy. CONCLUSIONS: TRUS-guided transperineal saturation re
      biopsy of the prostate using a 24-core scheme resulted in a high cancer detection
      rate also in patients who had had two or more previous biopsies. The total
      prostate volume was the only predictor of prostate cancer.

PMID- 19863532
TI  - Activity of ketoconazole after taxane-based chemotherapy in castration-resistant
      prostate cancer.
AB  - OBJECTIVE: To assess the efficacy of the androgen-synthesis inhibitor
      ketoconazole as a secondary hormonal therapy in patients with castration
      resistant prostate cancer (CRPC) previously treated with chemotherapy, as
      persistent androgens appear to play a role in the development and maintenance of
      CRPC. PATIENTS AND METHODS: We retrospectively identified 34 patients with CRPC
      who were treated with ketoconazole as a secondary hormonal therapy after
      paclitaxel- or docetaxel-based chemotherapy for CRPC. They were treated with
      ketoconazole 200-400 mg three times daily with or without hydrocortisone.
      Patients with previous use of ketoconazole were excluded. Half the patients had
      received estramustine as part of their chemotherapy regimen. The primary endpoint
      was the proportion of patients with a decline of > or =50% in their prostate
      specific antigen (PSA) level. PSA progression was defined by the PSA Working
      Group 1 Criteria. RESULTS: Eight of the 32 evaluable patients (25%) had a PSA
      decline of > or =50%. The median time to progression (TTP) was 3 months (95%
      confidence interval, 1.2-5.4). A history of previous response to taxane-based
      chemotherapy was not associated with the response to ketoconazole. However,
      previous use of oestrogens for CRPC was significantly associated with a shorter
      TTP on ketoconazole (1.5 vs 10.2 months; P = 0.03). CONCLUSIONS: Ketoconazole has
      moderate activity as secondary hormonal therapy in patients with CRPC previously
      treated with taxane-based chemotherapy, although the TTP was short. Previous
      treatment with oestrogenic therapy is associated with a shorter TTP.

PMID- 19863533
TI  - Lenalidomide in patients with refractory or multiple relapsed Hodgkin lymphoma.

PMID- 19863534
TI  - Growth differentiation factor 15 in anaemia of chronic disease, iron deficiency
      anaemia and mixed type anaemia.
AB  - Recently, the iron and erythropoiesis-controlled growth differentiation factor 15
      (GDF15) has been shown to inhibit the expression of hepcidin in beta-thalassaemia
      patients, thereby increasing iron absorption despite iron overload. To access the
      diagnostic and pathogenic impact of GDF15 in inflammatory anaemia the association
      of GDF15 expression with serum iron parameters and hepcidin was studied in
      patients suffering from iron deficiency anaemia (IDA), anaemia of chronic disease
      (ACD) and ACD subjects with true iron deficiency (ACD/IDA). GDF15 was
      significantly increased in both ACD and ACD/IDA, but not in IDA subjects as
      compared to controls. In contrast, hepcidin levels were significantly lower in
      IDA and ACD/IDA subjects than in ACD patients. IDA and ACD/IDA, but not ACD,
      showed an association between GDF15 and soluble transferrin receptor, an
      indicator of iron requirement for erythropoiesis. However, GDF15 did not
      correlate to hepcidin in either patient group. While GDF15 levels were linked to
      the needs for erythropoiesis and iron homeostasis in IDA, the immunity-driven
      increase of GDF15 may not primarily affect iron homeostasis and hepcidin
      expression. This indicates that other ACD-related factors may overcome the
      regulatory effects of GDF15 on hepcidin expression during inflammation.

PMID- 19863535
TI  - WASP plays a novel role in regulating platelet responses dependent on
      alphaIIbbeta3 integrin outside-in signalling.
AB  - The most consistent feature of Wiskott Aldrich syndrome (WAS) is profound
      thrombocytopenia with small platelets. The responsible gene encodes WAS protein
      (WASP), which functions in leucocytes as an actin filament nucleating agent -yet-
      actin filament nucleation proceeds normally in patient platelets regarding shape
      change, filopodia and lamellipodia generation. Because WASP localizes in the
      platelet membrane skeleton and is mobilized by alphaIIbbeta3 integrin outside-in
      signalling, we questioned whether its function might be linked to integrin.
      Agonist-induced alphaIIbbeta3 activation (PAC-1 binding) was normal for patient
      platelets, indicating normal integrin inside-out signalling. Inside-out
      signalling (fibrinogen, JON/A binding) was also normal for wasp-deficient murine
      platelets. However, adherence/spreading on immobilized fibrinogen was decreased
      for patient platelets and wasp-deficient murine platelets, indicating decreased
      integrin outside-in responses. Another integrin outside-in dependent response,
      fibrin clot retraction, involving contraction of the post-aggregation actin
      cytoskeleton, was also decreased for patient platelets and wasp-deficient murine
      platelets. Rebleeding from tail cuts was more frequent for wasp-deficient mice,
      suggesting decreased stabilisation of the primary platelet plug. In contrast,
      phosphatidylserine exposure, a pro-coagulant response, was enhanced for WASP
      deficient patient and murine platelets. The collective results reveal a novel
      function for WASP in regulating pro-aggregatory and pro-coagulant responses
      downstream of integrin outside-in signalling.

PMID- 19863537
TI  - Frequency of altered monoclonal protein production at relapse of multiple
      myeloma.

PMID- 19863536
TI  - Comprehensive analyses and characterization of haemophagocytic
      lymphohistiocytosis in Vietnamese children.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a fatal haematological disorder with
      diverse aetiology. This prospective study was undertaken to characterize HLH
      cases in Vietnamese children. Clinical and laboratory data, genetic analyses and
      outcome of the HLH patients were analysed. A total of 33 patients were enrolled
      from March 2007 to December 2008, with a median age of 3 years. Mutations of the
      SH2D1A (SAP) and PRF1 genes were detected in one patient, respectively. The virus
      association was high, up to 63.6% (21/33), including Epstein-Barr virus (19/33),
      cytomegalovirus (2/33) and dengue virus (2/33). Five patients had malignant
      lymphoma and two had autoimmune diseases. Twenty-eight patients were treated
      according to the HLH-2004 protocol. The first response rate was 64.3% (18/28),
      with an early death rate of 35.7% (10/28). High levels of interferon-gamma,
      interleukin-10, MIG and interferon-inducible protein-10 (IP-10) were associated
      with early mortality (P < 0.05). Reactivation among the responders was high
      (9/18) and the uneventful resolution was low (3/18) after a median follow-up of
      35 weeks. In conclusion, the majority of HLH cases are associated with virus
      infections in Vietnamese children. Familial HLH is rare. The frequent
      reactivation and high mortality demands a more appropriate therapeutic regimen in
      tropical areas like Vietnam.

PMID- 19863538
TI  - Minimal residual disease is a significant predictor of treatment failure in non T
      lineage adult acute lymphoblastic leukaemia: final results of the international
      trial UKALL XII/ECOG2993.
AB  - The predictive value of molecular minimal residual disease (MRD) monitoring using
      polymerase chain reaction amplification of clone-specific immunoglobulin or T
      cell Receptor rearrangements was analysed in 161 patients with non T-lineage
      Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK
      arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group
      (ECOG) 2993. MRD positivity (> or =10(-4)) in patients treated with chemotherapy
      alone was associated with significantly shorter relapse-free survival (RFS) at
      several time-points during the first year of therapy. MRD status best
      discriminated outcome after phase 2 induction, when the relative risk of relapse
      was 8.95 (2.85-28.09)-fold higher in MRD-positive (> or =10(-4)) patients and the
      5-year RFS 15% [95% confidence interval (CI) 0-40%] compared to 71% (56-85%) in
      MRD-negative (<10(-4)) patients (P = 0.0002) When MRD was detected prior to
      autologous stem cell transplantation (SCT), a significantly higher rate of
      treatment failure was observed [5-year RFS 25% (CI 0-55%) vs. 77% (95% CI 54
      100%) in MRD-negative/<10(-4), P = 0.01] whereas in recipients of allogeneic-SCT
      in first complete remission, MRD positivity pre-transplant did not adversely
      affect outcome. These data provide a rationale for introducing MRD-based risk
      stratification in future studies for the delineation of those at significant risk
      of treatment failure in whom intensification of therapy should be evaluated.

PMID- 19863539
TI  - Treatment with deferasirox (Exjade) effectively decreases iron burden in patients
      with thalassaemia intermedia: results of a pilot study.

PMID- 19863540
TI  - Insight into the molecular pathogenesis of hairy cell leukaemia, hairy cell
      leukaemia variant and splenic marginal zone lymphoma, provided by the analysis of
      their IGH rearrangements and somatic hypermutation patterns.

PMID- 19863541
TI  - Cell cycle and tissue of origin contribute to the migratory behaviour of human
      fetal and adult mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSC) are potential cells for cellular therapies, in
      which the recruitment and migration of MSC towards injured tissue is crucial. Our
      data show that culture-expanded MSC from fetal lung and bone marrow, adult bone
      marrow and adipose tissue contained a small percentage of migrating cells in
      vitro, but the optimal stimulus was different. Overall, fetal lung-MSC had the
      highest migratory capacity. As fetal bone marrow-MSC had lower migratory
      potential than fetal lung-MSC, the tissue of origin may determine the migratory
      capacity of MSC. No additive effect in migration towards combined stimuli was
      observed, which suggests only one migratory MSC fraction. Interestingly, actin
      rearrangement and increased paxillin phosphorylation were observed in most MSC
      upon stromal cell-derived factor-1alpha or platelet-derived growth factor-BB
      stimulation, indicating that this mechanism involved in responding to migratory
      cues is not restricted to migratory MSC. Migratory MSC maintained differentiation
      and migration potential, and contained significantly less cells in S- and G2/M
      phase than their non-migrating counterpart. In conclusion, our results suggest
      that MSC from various sources have different migratory capacities, depending on
      the tissue of origin. Similar to haematopoietic stem cells, cell cycle
      contributes to MSC migration, which offers perspectives for modulation of MSC to
      enhance efficacy of future cellular therapies.

PMID- 19863542
TI  - High resolution SNP array genomic profiling of peripheral T cell lymphomas, not
      otherwise specified, identifies a subgroup with chromosomal aberrations affecting
      the REL locus.
AB  - Little is known about genomic aberrations in peripheral T cell lymphoma, not
      otherwise specified (PTCL NOS). We studied 47 PTCL NOS by 250k GeneChip single
      nucleotide polymorphism arrays and detected genomic imbalances in 22 of the
      cases. Recurrent gains and losses were identified, including gains of chromosome
      regions 1q32-43, 2p15-16, 7, 8q24, 11q14-25, 17q11-21 and 21q11-21 (> or = 5
      cases each) as well as losses of chromosome regions 1p35-36, 5q33, 6p22, 6q16,
      6q21-22, 8p21-23, 9p21, 10p11-12, 10q11-22, 10q25-26, 13q14, 15q24, 16q22, 16q24,
      17p11, 17p13 and Xp22 (> or = 4 cases each). Genomic imbalances affected several
      regions containing members of nuclear factor-kappaB signalling and genes involved
      in cell cycle control. Gains of 2p15-16 were confirmed in each of three cases
      analysed by fluorescence in situ hybridization (FISH) and were associated with
      breakpoints at the REL locus in two of these cases. Three additional cases with
      gains of the REL locus were detected by FISH among 18 further PTCL NOS. Five of
      27 PTCL NOS investigated showed nuclear expression of the REL protein by
      immunohistochemistry, partly associated with genomic gains of the REL locus.
      Therefore, in a subgroup of PTCL NOS gains/rearrangements of REL and expression
      of REL protein may be of pathogenetic relevance.

PMID- 19863543
TI  - Ontogeny of haematopoiesis: recent advances and open questions.
AB  - Unravelling the embryonic origins of the haematopoietic system has been the
      subject of sustained research for more than a century. Nevertheless, many
      important questions are still either unanswered or remain a matter of intense
      debate. Recent progress in mouse and embryonic stem cell model systems as well as
      imaging and post-genomic technologies has provided new insights into many of
      these open questions. Here we place into context recent reports on the anatomical
      site of blood stem cell emergence and, using red blood cells as an example,
      illustrate how the development of stem cells and the other blood lineages is both
      temporally and spatially decoupled. In addition, we outline how embryonic stem
      cell assays are increasingly used as a powerful surrogate for studying lineage
      relationships and developmental potential of early embryonic blood progenitors.
      Finally, we review how recent progress in the reconstruction of transcriptional
      regulatory networks is beginning to define the connectivity between key
      regulators that control early blood development. In light of these rapid recent
      advances, research into the embryonic origins of the haematopoietic system should
      remain one of the most vibrant disciplines within the wider field of haematology
      for the foreseeable future.

PMID- 19863545
TI  - Sudden death: ethical and legal problems of post-mortem forensic genetic testing
      for hereditary cardiac diseases.
AB  - Hereditary non-structural diseases such as catecholaminergic polymorphic
      ventricular tachycardia (CPVT), long QT, and the Brugada syndrome as well as
      structural disease such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic
      right ventricular cardiomyopathy (ARVC) cause a significant percentage of sudden
      cardiac deaths in the young. In these cases, genetic testing can be useful and
      does not require proxy consent if it is carried out at the request of judicial
      authorities as part of a forensic death investigation. Mutations in several genes
      are implicated in arrhythmic syndromes, including SCN5A, KCNQ1, KCNH2, RyR2, and
      genes causing HCM. If the victim's test is positive, this information is
      important for relatives who might be themselves at risk of carrying the disease
      causing mutation. There is no consensus about how professionals should proceed in
      this context. This article discusses the ethical and legal arguments in favour of
      and against three options: genetic testing of the deceased victim only;
      counselling of relatives before testing the victim; counselling restricted to
      relatives of victims who tested positive for mutations of serious and preventable
      diseases. Legal cases are mentioned that pertain to the duty of geneticists and
      other physicians to warn relatives. Although the claim for a legal duty is
      tenuous, recent publications and guidelines suggest that geneticists and others
      involved in the multidisciplinary approach of sudden death (SD) cases may,
      nevertheless, have an ethical duty to inform relatives of SD victims. Several
      practical problems remain pertaining to the costs of testing, the counselling and
      to the need to obtain permission of judicial authorities.

PMID- 19863544
TI  - Purple sweet potato color alleviates D-galactose-induced brain aging in old mice
      by promoting survival of neurons via PI3K pathway and inhibiting cytochrome C
      mediated apoptosis.
AB  - Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins,
      protects brain function against oxidative stress induced by D-galactose (D-gal)
      (Sigma-Aldrich, St. Louis, MO, USA). Our data showed that PSPC enhanced open
      field activity, decreased step-through latency, and improved spatial learning and
      memory ability in D-gal-treated old mice by decreasing advanced glycation end
      products' (AGEs) formation and the AGE receptor (RAGE) expression, and by
      elevating Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (Sigma-Aldrich) and catalase
      (CAT) expression and activity. Cleavage of caspase-3 and increased terminal
      deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick
      end-labeling (TUNEL)-positive cells in D-gal-treated old mice were inhibited by
      PSPC, which might be attributed to its antioxidant property. PSPC also suppressed
      the activation of c-Jun NH(2)-terminal kinase (JNK) and the release of cytochrome
      c from mitochondria that counteracted the onset of neuronal apoptosis in D-gal
      treated old mice. Furthermore, it was demonstrated that phosphoinositide 3-kinase
      (PI3K) activation was required for PSPC to promote the neuronal survival
      accompanied with phosphorylation and activation of Akt and p44/42 mitogen
      activated protein kinase (MAPK) by using PI3K inhibitor LY294002 (Cell Signaling
      Technology, Inc., Beverly, MA, USA), implicating a neuronal survival mechanism.
      The present results suggest that neuronal survival promoted by PSPC may be a
      potentially effective method to enhance resistance of neurons to age-related
      disease.

PMID- 19863546
TI  - Novel PORCN mutations in focal dermal hypoplasia.
AB  - Focal dermal hypoplasia (FDH), Goltz or Goltz-Gorlin syndrome, is an X-linked
      dominant multisystem disorder characterized primarily by involvement of the skin,
      skeletal system and eyes. We screened for mutations in the PORCN gene in eight
      patients of Belgian and Finnish origin with firm clinical suspicion of FDH.
      First, we performed quantitative PCR (qPCR) analysis to define the copy number at
      this locus. Next, we sequenced the coding regions and flanking intronic sequences
      of the PORCN gene. Three de novo mutations were identified in our patients with
      FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and
      X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon
      11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed
      highly conserved amino acids and were not found in 300 control X chromosomes. The
      three patients in whom mutations were identified all present with characteristic
      dermal findings together with limb manifestations, which were not seen in our
      mutation-negative patients. The clinical characteristics of our patients with
      PORCN mutations were compared with the previously reported mutation-positive
      cases. In this report, we summarize the literature on PORCN mutations and
      associated phenotypes.

PMID- 19863547
TI  - Screening and instability of FMR1 alleles in a prospective sample of 24,449
      mother-newborn pairs from the general population.
AB  - To study the instability of FMR1 triplet repeats in the general population, we
      screened a prospective sample of 24,449 anonymized mother-offspring pairs and
      analyzed transmissions of intermediate-size (45-54 triplets) and premutation-size
      (55-200 triplets) alleles. We screened all mothers for alleles > or = 45 triplets
      by Southern blot and studied transmission of 545 maternal alleles to their
      offspring using polymerase chain reaction. Out of 21,411 maternal samples with
      conclusive results, we identified 250 carriers of at least one intermediate-size
      allele and 39 carrying a premutation-size allele. Out of a subsample of 430
      transmissions of normal-size alleles (< 45 triplets), we observed four (< 1%)
      unstable transmissions. There were 6/90 intermediate-size unstable alleles (7%)
      and 11/25 unstable premutation-size alleles (44%). Two mothers transmitted a
      typical full mutation. The incidence of fragile X syndrome was thus 1/12,225
      newborns (upper limit of 95% confidence interval: 1/4638 newborns), but larger in
      males (1/6209) than females (none detected in over 12,000 newborn females).
      Intermediate-size alleles were more unstable than normal-size alleles (p =
      0.0027), but more stable (about sixfold) than premutation-size alleles (p <
      0.0001). Unstable premutation-size alleles harbored the major fragile X haplotype
      (T50-T42-T62), and this haplotype appeared to be a good predictor of instability
      in premutations (p = 0.02). Incidence and instability are important to determine
      the feasibility and cost effectiveness of putative FMR1 screening programs.
      Carriers of FMR1 alleles of 55+ triplets with no family history of the disease
      may have a significant risk of expansion to a full mutation in a single
      generation.

PMID- 19863548
TI  - Multiple spinal ganglioneuromas in a patient harboring a pathogenic NF1 mutation.
AB  - Ganglioneuroma is a rare benign tumor originating from autonomic ganglia and is
      considered the benign counterpart of neuroblastoma. Ganglioneuromas may be
      present as an isolated finding and, rarely, in association with neurofibromatosis
      type 1 (NF1). However, ganglioneuromas of the cervical spine with intradural
      extension and multiple locations are extremely rare. We describe a 32-year-old
      woman with multiple ganglioneuromas of the cervical, dorsal and lumbar spine
      associated with a few cafe-au-lait spots and subcutaneous nodules. The patient
      lacked other NF1 stigmata, such as freckling, Lisch nodules and cutaneous
      neurofibromas. Although our patient did not fulfill the NF1 diagnostic criteria,
      molecular diagnosis revealed a pathogenic mutation in the NF1 gene. Approximately
      30 patients affected by NF1 and ganglioneuromas have been reported: in all these
      individuals, NF1 diagnosis was made according to the clinical diagnostic criteria
      and no patients have molecular diagnosis. Therefore, this is the first case with
      multiple spinal ganglioneuromas associated with a pathogenic NF1 mutation.

PMID- 19863549
TI  - Detailed molecular and clinical characterization of three patients with 21q
      deletions.
AB  - We have investigated three patients with 21q deletions, two with developmental
      delay, dysmorphic features and internal organ malformations, and one with
      cognitive function within the normal range but with some deficits in gross and
      fine motor development. All aberrations were characterized by array-comparative
      genomic hybridization (array-CGH). In addition, extensive fluorescence in situ
      hybridization (FISH) mapping on metaphase chromosomes and mechanically stretched
      chromosomes was performed on patient 1 who had an extremely complex
      intrachromosomal rearrangement with 16 breakpoints, four deletions and four
      duplications. Patients 2 and 3 had interstitial deletions comprising 21q21.1
      21q22.11 and 21q11.2-21q21.3, respectively. Partial deletions of 21q are rare and
      these patients display a highly variable phenotype depending on the size and
      position of the deletion. A review of the literature identified 38 cases with
      pure 21q deletions. Twenty-three of these had reliable mapping data. The combined
      information of present and previous cases suggests that the ITSN1 gene is
      involved in severe mental retardation in patients with 21q deletion. In addition,
      a critical region of 0.56 Mb containing four genes, KCNE1, DSCR1, CLIC6 and
      RUNX1, is associated with severe congenital heart defects, and deletions of the
      most proximal 15-17 Mb of 21q is associated with mild or no cognitive impairment,
      but may lead to problems with balance and motor function.

PMID- 19863550
TI  - Clinical and genetic analysis of Korean patients with Marfan syndrome: possible
      ethnic differences in clinical manifestation.
AB  - Marfan syndrome (MFS) is an autosomal dominant disorder of the fibrous connective
      tissue caused by mutations in the fibrillin-1 (FBN1) gene. Although clinical and
      genetic analyses have been performed in various populations, there have been few
      studies in Korea. The aim of this study was to investigate the clinical
      characteristics and genetic background of Korean patients with MFS. In 39 Korean
      patients with MFS who met the Ghent criteria, the most common clinical finding
      was aortic dilatation and/or dissection (94.9%), whereas only 35.9% of patients
      had ectopia lentis. The majority of MFS patients had fewer than four of the
      skeletal findings required to fulfill the major skeletal Ghent criterion for MFS.
      Only 21% of Korean patients had major skeletal abnormalities and most cases
      showed only minor skeletal involvement. FBN1 gene mutations were detected in 35
      out of 39 patients (89.7%), which is similar to rates presented in the previous
      reports. These results suggest that some clinical features in Korean patients
      with MFS differed from those reported in Western MFS patients.

PMID- 19863551
TI  - Role of genetic testing in arrhythmogenic right ventricular
      cardiomyopathy/dysplasia.
AB  - In a cohort of patients with confirmed or suspected arrhythmogenic right
      ventricular cardiomyopathy/dysplasia (ARVC/D), genetic testing is useful in
      confirming the diagnosis, particularly in individuals who do not completely
      fulfil Task Force criteria for the disease, thereby also enabling the adoption of
      preventive measures in family members. Due to the high percentage of novel
      mutations that are expected to be identified in ARVC/D, the use of genetic
      screening technology based on the identification of known mutations seems to have
      very restricted value. Our results support that the presence of certain genetic
      variations could play a role in the final phenotype of patients with ARVC/D,
      where single and compound mutation carriers would have more symptomatic forms of
      the disease and the polymorphism P366L could be associated to a more benign
      phenotype.

PMID- 19863552
TI  - Surveillance in von Hippel-Lindau disease (vHL).
AB  - von Hippel-Lindau disease (vHL) is a hereditary multisystem cancer syndrome
      requiring lifelong prophylactic surveillance. Current surveillance
      recommendations rely on best medical judgement and no evidence of effect exists.
      We aimed to evaluate the capability of surveillance in manifestation detection,
      before these turn symptomatic, in order to prevent disabling or even fatal
      outcomes. We focus on surveillance of central nervous system (CNS)
      hemangioblastomas, retinal hemangiomas and renal cell carcinoma (RCC) as these
      have the most severe consequences. On the basis of full medical records from 54
      living vHL-mutation carriers, risks of intercurrent manifestations in-between
      surveillance examinations were determined and clinical consequences of
      surveillance findings evaluated. Current recommendations of annual ophthalmic and
      abdominal examinations corresponded to acceptably low intercurrent manifestation
      risks (1.7% and 1.2%, respectively), whereas recommendations of biennial CNS
      imaging corresponded to a risk of 7.2%. Annual CNS examinations, however,
      significantly reduces this risk to 2.7%. Furthermore, most CNS manifestations
      found due to surveillance (71%, 106 of 150) had clinical consequence for the
      patient. Also, pre-symptomatic surveillance increased cumulative incidence of
      clinical vHL diagnosis from 46% to 72% and from 89% to 94% by age 30 and 50
      years, respectively. The present results promote optimization of surveillance,
      expectantly improving clinical vHL outcomes.

PMID- 19863553
TI  - Modulation of caspases and their non-apoptotic functions by Legionella
      pneumophila.
AB  - Legionella pneumophila has become a model system to decipher the non-apoptotic
      functions of caspases and their role in immunity. In permissive cells, the L.
      pneumophila-containing vacuole evades endosomal traffic and is remodelled by the
      endoplasmic reticulum. Evasion of the endosomes is mediated by the Dot/Icm type
      IV secretion system. Upon L. pneumophila infection of genetically restrictive
      cells such as wild-type (WT) C57Bl/6J murine macrophages, flagellin is sensed by
      the NOD-like receptor Nlrc4 leading to caspase-1 activation by the inflammasome
      complex. Then, caspase-7 is activated downstream of the Nlrc4 inflammasome,
      promoting non-apoptotic functions such as L. pneumophila-containing phagosome
      maturation and bacterial degradation. Interestingly, caspase-3 is activated in
      permissive cells during early stages of infection. However, caspase-3 activation
      does not lead to apoptosis until late stages of infection because it is
      associated with potent Dot/Icm-mediated anti-apoptotic stimuli that render the
      infected cells resistant to external apoptotic inducers. Therefore, the role of
      caspase-1 and non-apoptotic functions of executioner caspases are temporally and
      spatially modulated during infection by L. pneumophila, which determine
      permissiveness to intracellular bacterial proliferation. This review will examine
      the novel activation pathways of caspases by L. pneumophila and discuss their
      role in genetic restriction and permissiveness to infection.

PMID- 19863554
TI  - Cell biology and molecular ecology of Francisella tularensis.
AB  - Francisella tularensis is a highly infectious intracellular bacterium that causes
      the fulminating disease tularemia, which can be transmitted between mammals by
      arthropod vectors. Genomic studies have shown that the F. tularensis has been
      undergoing genomic decay with the most virulent strains having the lowest number
      of functional genes. Entry of F. tularensis into macrophages is mediated by
      looping phagocytosis and is associated with signalling through Syk tyrosine
      kinase. Within macrophages and arthropod-derived cells, the Francisella
      containing phagosome matures transiently into an acidified late endosome-like
      phagosome with limited fusion to lysosomes followed by rapid bacterial escape
      into the cytosol within 30-60 min, and bacterial proliferation within the
      cytosol. The Francisella pathogenicity island, which potentially encodes a
      putative type VI secretion system, is essential for phagosome biogenesis and
      bacterial escape into the cytosol within macrophages and arthropod-derived cells.
      Initial sensing of F. tularensis in the cytosol triggers IRF-3-dependent IFN-beta
      secretion, type I IFNR-dependent signalling, activation of the inflammasome
      mediated by caspase-1, and a pro-inflammatory response, which is suppressed by
      triggering of SHIP. The past few years have witnessed a quantum leap in our
      understanding of various aspects of this organism and this review will discuss
      these remarkable advances.

PMID- 19863555
TI  - Positioning of large organelles by a membrane- associated cytoskeleton in
      Plasmodium sporozoites.
AB  - Cellular organelles are usually linked to the cytoskeleton, which often provides
      a scaffold for organelle function. In malaria parasites, no link between the
      cytoskeleton and the major organelles is known. Here we show that during fast,
      stop-and-go motion of Plasmodium sporozoites, all organelles stay largely fixed
      in respect to the moving parasite. Cryogenic electron tomography reveals that the
      nucleus, mitochondrion, apicoplast and the microtubules of Plasmodium sporozoites
      are linked to the parasite pellicle via long tethering proteins. These tethers
      originate from the inner membrane complex and are arranged in a periodic fashion
      following a 32 nm repeat. The tethers pass through a subpellicular structure that
      encompasses the entire parasite, probably as a network of membrane-associated
      filaments. While the spatial organization of the large parasite organelles
      appears dependent on their linkage to the cortex, the specialized secretory
      vesicles are mostly not linked to microtubules or other cellular structures that
      could provide support for movement.

PMID- 19863556
TI  - Caenorhabditis is a metazoan host for Legionella.
AB  - We investigated whether nematodes contribute to the persistence, differentiation
      and amplification of Legionella species in soil, an emerging source for
      Legionnaires' disease. Here we show that Legionella spp. colonize the intestinal
      tracts of Caenorhabditis nematodes leading to worm death. Susceptibility to
      Legionella is influenced by innate immune responses governed by the p38 mitogen
      activated protein kinase and insulin/insulin growth factor-1 receptor signalling
      pathways. We also show that L. pneumophila colonizes the intestinal tract of
      nematodes cultivated in soil. To distinguish between transient infection and
      persistence, plate-fed and soil-extracted nematodes-fed fluorescent strains of L.
      pneumophila were analysed. Bacteria replicated within the nematode intestinal
      tract, did not invade surrounding tissue, and were excreted as differentiated
      forms that were transmitted to offspring. Interestingly, the ultrastructural
      features of the differentiated bacterial forms were similar to cyst-like forms
      observed within protozoa, amoeba and mammalian cell lines. While intestinal
      colonization of L. pneumophila dotA and icmT mutant strains did not alter the
      survival rate of nematodes in comparison to wild-type strains, nematodes
      colonized with the dot/icm mutant strains exhibited significantly increased
      levels of germline apoptosis. Taken together, these studies show that nematodes
      may serve as natural hosts for these organisms and thereby contribute to their
      dissemination in the environment and suggest that the remarkable ability of L.
      pneumophila to subvert host cell signalling and evade mammalian immune responses
      evolved through the natural selection associated with cycling between protozoan
      and metazoan hosts.

PMID- 19863558
TI  - Differential IFN-alpha/beta production suppressing capacities of the leader
      proteins of mengovirus and foot-and-mouth disease virus.
AB  - Picornaviruses encompass a large family of RNA viruses. Some picornaviruses
      possess a leader (L) protein at the N-terminus of their polyprotein. The L
      proteins of encephalomyocarditis virus, a cardiovirus, and foot-and-mouth disease
      virus (FMDV), an aphthovirus, are both dispensable for replication and their
      major function seems to be the suppression of antiviral host cell responses.
      Previously, we showed that the L protein of mengovirus, a strain of
      encephalomyocarditis virus, inhibits antiviral responses by inhibiting type I
      interferon (IFN-alpha/beta) gene transcription. The L protein of the FMDV is a
      protease (L(pro)) that cleaves cellular factors to reduce cytokine and chemokine
      mRNA production and to inhibit cap-dependent cellular host mRNA translation,
      thereby limiting the production of proteins with antiviral activity. In this
      study, we constructed a viable chimeric mengovirus that expresses FMDV L(pro) in
      place of the authentic L protein in order to compare the efficiency of the immune
      evasion mechanisms mediated by L and L(pro) respectively. We show that in this
      mengovirus background the L protein is more potent than FMDV L(pro) in
      suppressing IFN-alpha/beta responses. Yet, FMDV L(pro) is important to antagonize
      infection-limiting responses both in vitro and in vivo.

PMID- 19863557
TI  - The Pseudomonas syringae type III effector HopG1 targets mitochondria, alters
      plant development and suppresses plant innate immunity.
AB  - The bacterial plant pathogen Pseudomonas syringae uses a type III protein
      secretion system to inject type III effectors into plant cells. Primary targets
      of these effectors appear to be effector-triggered immunity (ETI) and pathogen
      associated molecular pattern (PAMP)-triggered immunity (PTI). The type III
      effector HopG1 is a suppressor of ETI that is broadly conserved in bacterial
      plant pathogens. Here we show that HopG1 from P. syringae pv. tomato DC3000 also
      suppresses PTI. Interestingly, HopG1 localizes to plant mitochondria, suggesting
      that its suppression of innate immunity may be linked to a perturbation of
      mitochondrial function. While HopG1 possesses no obvious mitochondrial signal
      peptide, its N-terminal two-thirds was sufficient for mitochondrial localization.
      A HopG1-GFP fusion lacking HopG1's N-terminal 13 amino acids was not localized to
      the mitochondria reflecting the importance of the N-terminus for targeting.
      Constitutive expression of HopG1 in Arabidopsis thaliana, Nicotiana tabacum
      (tobacco) and Lycopersicon esculentum (tomato) dramatically alters plant
      development resulting in dwarfism, increased branching and infertility.
      Constitutive expression of HopG1 in planta leads to reduced respiration rates and
      an increased basal level of reactive oxygen species. These findings suggest that
      HopG1's target is mitochondrial and that effector/target interaction promotes
      disease by disrupting mitochondrial functions.

PMID- 19863559
TI  - Cellular interactions of Candida albicans with human oral epithelial cells and
      enterocytes.
AB  - The human pathogenic fungus Candida albicans can cause systemic infections by
      invading epithelial barriers to gain access to the bloodstream. One of the main
      reservoirs of C. albicans is the gastrointestinal tract and systemic infections
      predominantly originate from this niche. In this study, we used scanning electron
      and fluorescence microscopy, adhesion, invasion and damage assays, fungal mutants
      and a set of fungal and host cell inhibitors to investigate the interactions of
      C. albicans with oral epithelial cells and enterocytes. Our data demonstrate that
      adhesion, invasion and damage by C. albicans depend not only on fungal morphology
      and activity, but also on the epithelial cell type and the differentiation stage
      of the epithelial cells, indicating that epithelial cells differ in their
      susceptibility to the fungus. C. albicans can invade epithelial cells by induced
      endocytosis and/or active penetration. However, depending on the host cell faced
      by the fungus, these routes are exploited to a different extent. While invasion
      into oral cells occurs via both routes, invasion into intestinal cells occurs
      only via active penetration.

PMID- 19863560
TI  - The contribution of founder mutations to early-onset breast cancer in French
      Canadian women.
AB  - In an ethnically-homogeneous population, it is valuable to identify founder
      mutations in cancer-predisposing genes. Founder mutations have been found in four
      breast-cancer-predisposing genes in French-Canadian breast cancer families. The
      frequencies of the mutant alleles have been measured neither in a large series of
      unselected breast cancer patients from Quebec, nor in healthy controls. These
      estimates are necessary to measure their contribution to the hereditary burden of
      breast cancer in Quebec and to help develop genetic screening policies which are
      appropriate for the province. We studied 564 French-Canadian women with early
      onset invasive breast cancer who were treated at a single Montreal hospital.
      Patients had been diagnosed at age 50 or less, and were ascertained between 2004
      and 2008. We screened all 564 patients for nine founder mutations: four in BRCA1,
      three in BRCA2 and one each in PALB2 and CHEK2. We also studied 6433 DNA samples
      from newborn infants from the Quebec City area to estimate the frequency of the
      nine variant alleles in the French-Canadian population. We identified a mutation
      in 36 of the 564 breast cancer cases (6.4%) and in 35 of 6443 controls (0.5%). In
      the breast cancer patients, the majority of mutations were in BRCA2 (54%).
      However, in the general population (newborn infants), the majority of mutations
      were in CHEK2 (54%). The odds ratio for breast cancer to age 50, given a BRCA1
      mutation, was 10.1 (95% CI: 3.7-28) and given a BRCA2 mutation was 29.5 (95% CI:
      12.9-67). The odds ratio for breast cancer to age 50, given a CHEK2 mutation, was
      3.6 (95% CI: 1.4-9.1). One-half of the women with a mutation had a first- or
      second-degree relative diagnosed with breast or ovarian cancer. Thus, it can be
      concluded that a predisposing mutation in BRCA1, BRCA2, CHEK2 or PALB2 is present
      in approximately 6% of French-Canadian women with early-onset breast cancer. It
      is reasonable to offer screening for founder mutations to all French-Canadian
      women with breast cancer before age 50. The frequency of these mutations in the
      general population (0.5%) is too low to advocate population-based screening.

PMID- 19863561
TI  - Combined immunodeficiency, facial dysmorphism, optic nerve atrophy, skeletal
      anomalies and developmental delay: a new syndrome.
AB  - Combined immunodeficiency (SCID) can be isolated and involve the immune system
      only or associated with abnormalities affecting other organs, mainly the skeletal
      and neurological systems. We report on sisters, born to consanguineous parents,
      with CID, facial dysmorphism, developmental delay, optic atrophy, myoclonic
      seizures, and skeletal anomalies. To the best of our knowledge, this is a
      hitherto new syndrome with most probably autosomal recessive inheritance and
      unknown etiology.

PMID- 19863562
TI  - MEFV mutations in Iranian Azeri Turkish patients with familial Mediterranean
      fever.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory
      disorder with more than 60 disease-associated mutations in the responsible gene,
      MEFV. In the present study, we determined 15 MEFV mutations in Iranian Azeri
      Turkish FMF patients. Five hundred and twenty-four unrelated patients were tested
      for 15 known mutations in the MEFV gene using amplification refractory mutation
      system-polymerase chain reaction and polymerase chain reaction-restriction
      fragment length polymorphism methods. Thirty-five different genotypes were
      characterized among the studied patients. Of the alleles investigated, the most
      common mutation was p.M694V (42.4%), followed by p.V726A (17%), p.E148Q (16.2%),
      and p.M680I (c.2040G>C) (15.2%). The p.R761H mutation (4.7%) was found to be the
      most frequent among the rare mutations. The mutations p.M680I (c.2040G>A),
      p.I692del, p.M694del and p.K695R were not found in this cohort. The remaining
      mutations account for 7.7% of the identifiable mutations. Five different types of
      complex alleles were also identified. The results show the diversity and the
      frequency of the mutations in the Iranian Azeri Turkish FMF patients. The p.R761H
      mutation is rather prevalent in Azeri Turks; therefore, it should be included in
      the routine molecular diagnosis of FMF patients from this ethnic group.

PMID- 19863563
TI  - Analysis of the CTNS gene in 32 cystinosis patients from Spain.

PMID- 19863565
TI  - Financing of internal displacement: excerpts from the Sri Lankan experience.
AB  - This paper investigates how internally displaced persons (IDPs) in Batticaloa,
      Sri Lanka, financed their first year of displacement. We conducted extensive
      fieldwork in August 2007 in numerous welfare centres in Batticaloa that have
      received persons displaced from the Mutur divisional secretariat (DS) in the
      Trincomalee district. The sample was selected from the village of Sampur in Mutur
      DS. The displaced from Sampur are of Tamil origin and our findings reveal certain
      coping strategies that may be particular to this community, including the selling
      or mortgaging of gold jewellery to address the effects of displacement. We found
      that the IDPs in this region rely heavily on jewellery and other forms of savings
      to ensure their survival. There is also strong evidence to support the critically
      important coping role played by livelihoods. These coping strategies have enabled
      the IDP households in the present sample to live marginally above the poverty
      line.

PMID- 19863564
TI  - Patterns of substance use among hurricane Katrina evacuees in Houston, Texas.
AB  - This paper focuses on changing patterns of substance use among low income,
      African American drug users evacuated from New Orleans, Louisiana, during
      Hurricane Katrina of August 2005. It examines the relationship between increases
      and decreases in alcohol and tobacco (AT) use and illicit drug (ID) use after
      Katrina and pre-disaster and within-disaster factors. Data from structured
      interviews with 200 Katrina evacuees currently living in Houston were collected 8
      14 months after the disaster. Multivariate analysis revealed that rises in AT use
      were positively associated with education. Females and younger evacuees were more
      likely to have increased AT use. ID use increase was positively associated with
      resource loss and leaving the city before Katrina. Decreases in AT and ID use
      were found to be associated with disaster-related exposure. The paper discusses
      the specific consequences of disasters on disadvantaged minority substance users
      and the importance of developing public health disaster policies that target this
      population.

PMID- 19863566
TI  - Targeting vulnerability after the 2005 earthquake: Pakistan's livelihood support
      cash grants programme.
AB  - The 7.6 magnitude (Richter scale) earthquake that struck northern Pakistan on 8
      October 2005 was devastating. This paper gauges success in targeting vulnerable
      families during the transition from relief to reconstruction through cash
      assistance provided by the Livelihood Support Cash Grants (LSCG) programme.
      Families without a male member, with a disabled male member aged between 18 and
      60 years or with more than five children, defined as vulnerable, were provided
      with USD 50 per month for six months via a bank transfer. The LSCG scheme
      enrolled around 750,000 families and selected 267,402 vulnerable families to whom
      it disbursed a total of USD 86.95 million. Using a community-based survey, this
      paper assesses leakage and under-coverage (exclusion). Approximately 30 per cent
      of families received the cash grant. However, only one in two was eligible for
      the benefit, and one in two deserving families was excluded. This is a matter of
      grave concern.

PMID- 19863567
TI  - Organisational socialisation in a crisis context.
AB  - The objective of this paper is to highlight the dimensions characterising the
      socialisation process in a crisis context. Based on the definition of
      organisational socialisation advanced by Van Maanen and Schein (1979) and
      employed later by Jones (1986), a crisis is presented as a passage from a
      'normal' situation to an 'exceptional' situation. A crisis represents a
      socialisation context in the sense that it is a novel state in which actors must
      develop a different way of mobilising their knowledge, utilising their skills,
      and practicing their trade or profession. The paper discusses certain findings
      that have emerged from the literature on organisational socialisation, as well as
      from the testimony of actors who participated in efforts to manage the Quebec ice
      storm crisis of early 1998. It is hoped that this exploratory study's data will
      give rise to fruitful interaction between the field of organisational
      socialisation and that of crisis management.

PMID- 19863568
TI  - Urban earthquake hazard: perceived seismic risk and preparedness in Dhaka City,
      Bangladesh.
AB  - Bangladesh is vulnerable to seismic events. Experts suspect that if an earthquake
      with a 7.0 magnitude occurred in large cities of Bangladesh, there would be a
      major human tragedy due to the structural failure of many buildings. The primary
      objectives of this paper are to examine seismic risk perception among residents
      of Dhaka City and investigate their levels of earthquake preparedness. A
      questionnaire survey conducted among 444 residents of the city provided the major
      source of data for the paper. The survey results suggest that an overwhelming
      majority of the respondents were not prepared for a major earthquake, which is
      anticipated to occur in Dhaka. Multivariate analysis of survey data reveals that
      value of residential unit and respondent educational levels appear as the most
      significant determinants of preparedness status of the respondents. This study
      recommends increasing earthquake awareness and preparedness among residents of
      Dhaka City.

PMID- 19863569
TI  - Lessons from a microfinance recapitalisation programme.
AB  - Following a major disaster, microfinance institutions (MFIs) often face high
      levels of bad debt, which may require the institutions to be recapitalised. This
      paper describes a recapitalisation programme implemented by the SANASA movement
      of Sri Lanka in 390 microfinance societies following the December 2004 tsunami,
      and highlights lessons for other similar programmes. MFI recapitalisation is a
      good use of funds in post-disaster situations. To create successful programmes,
      donors should expect to relax some of their usual project requirements and MFIs
      should focus on maintaining credit discipline.

PMID- 19863570
TI  - Urban disaster recovery: a measurement framework and its application to the 1995
      Kobe earthquake.
AB  - This paper provides a framework for assessing empirical patterns of urban
      disaster recovery through the use of statistical indicators. Such a framework is
      needed to develop systematic knowledge on how cities recover from disasters. The
      proposed framework addresses such issues as defining recovery, filtering out
      exogenous influences unrelated to the disaster, and making comparisons across
      disparate areas or events. It is applied to document how Kobe City, Japan,
      recovered from the catastrophic 1995 earthquake. Findings indicate that while
      aggregate population regained pre-disaster levels in ten years, population had
      shifted away from the older urban core. Economic recovery was characterised by a
      three to four year temporary boost in reconstruction activities, followed by
      settlement at a level some ten per cent below pre-disaster levels. Other long
      term effects included substantial losses of port activity and sectoral shifts
      toward services and large businesses. These patterns of change and disparity
      generally accelerated pre-disaster trends.

PMID- 19863571
TI  - Community cohesion after a natural disaster: insights from a Carlisle flood.
AB  - This project analysed changes in community cohesion following a natural disaster.
      Data were collected from a flood-affected community using a questionnaire survey.
      Analyses revealed that community cohesion was not predicted by the length of
      residence, or any other demographic characteristic of residents, but rather by a
      sense of community, community cognition and the degree of community
      participation. Cohesion alteration was not uniform, but varied along levels of
      hazard severity (degree of flood invasion). Cohesion increased in line with
      hazard severity at the initial flood stage, as residents recognised the
      importance of community unity and came together to cope with their losses. When
      the severity increased, residents transferred their focus to individual
      interests, which resulted in decreased cohesion. This project distinguishes
      itself in examining community cohesion in the wake of a natural disaster in the
      real world. Implications regarding community reconstruction and suggestions for
      hazard researchers are discussed accordingly.

PMID- 19863572
TI  - Thyroid function and morphology in subjects with microdeletion of chromosome
      22q11 (del(22)(q11)).
AB  - INTRODUCTION: Monoallelic microdeletion of chromosome 22q11 (22q11DS) is
      considered to be the commonest human microdeletion syndrome. Abnormalities of
      thyroid function are sporadically reported in this syndrome, but very few studies
      have specifically assessed this issue, and thyroid morphology has not been
      systematically studied. DESIGN: To evaluate the prevalence of abnormalities of
      thyroid function and morphology in a cohort of paediatric and adult patients with
      22q11DS. METHODS: Thirty patients with 22q11DS (median age 9.7, range 1.5-43.9
      years) were studied. In all subjects, serum free-T(3), free-T(4), TSH,
      thyroperoxidase, thyroglobulin, and TSHr auto-antibodies, as well as thyroid
      ultrasonographic data, were evaluated and compared with age- and sex-matched
      healthy control groups, for paediatric and adult patients. RESULTS: Fourteen
      (46.6%) patients showed thyroid hypoplasia involving the entire gland. In all the
      patients, the volume of the left lobe of the thyroid was significantly reduced (P
      < 0.01). Among the subjects with thyroid hypoplasia, 10 out of 14 (71%) showed a
      concomitant heart malformation, a condition that was present in five (31%) of the
      subjects with a normal thyroid volume (P < 0.05). Seven (23.3%) cases of
      subclinical hypothyroidism and one (3.3%) case of overt hypothyroidism were
      identified. Three (10%) patients were positive for thyroid auto-antibodies. Of
      the patients with overt and subclinical hypothyroidism, five out of eight (62.5%)
      patients showed thyroid hypoplasia. CONCLUSIONS: This study confirms the presence
      of alterations of thyroid function in 22q11DS, and also suggests a frequent
      occurrence of abnormalities in thyroid morphology in these subjects. Patients
      with 22q11DS should be monitored for thyroid function, and thyroid ultrasound
      screening should be considered, especially in those patients with changes in
      thyroid function or congenital heart malformations. The possible relationship
      between developmental abnormalities in the heart and the thyroid gland should be
      confirmed.

PMID- 19863573
TI  - Leuprolide acetate gonadotrophin response patterns during female puberty.
AB  - OBJECTIVE: To assess normative data and the usefulness of spontaneous and LHRH
      analogue-stimulated serum LH and FSH levels measured by immunoradiometric assays
      (IRMA) in the evaluation of normal puberty. DESIGN: Prospective. Healthy girls in
      Tanner I and Tanner II from the local community were invited to participate (n =
      47). METHODS: A leuprolide acetate test (500 mcg/m(2); sc) was performed. LH and
      FSH levels were determined using IRMA. Tanner II girls were assessed every 6
      months until Tanner V. Girls who progressed from Tanner II to Tanner III in the
      next 6 months were called Tanner II-2; otherwise, they were called Tanner II-1.
      RESULTS: The prepubertal upper limit (CI 95%) was 0.49 IU/l for basal LH and 5.1
      IU/l for stimulated LH. Taking into account these LH cut-off limits, 72.2% and
      66.7% of Tanner II-1 and 41.6% and 41.7% of Tanner II-2 subjects presented
      overlapping values for basal and stimulated LH, respectively, as compared with
      the Tanner I group. The cut-offs for basal and stimulated LH to predict
      progression from Tanner II to Tanner III in the next 6 months were a basal LH
      level > or =0.49 IU/l (Sensitivity = 0.58; 1-Specificity = 0.33) and a
      poststimulated LH level > or =4.75 IU/l (Sensitivity = 0.67; 1-Specificity =
      0.44). CONCLUSION: According to an IRMA, the basal and leuprolide acetate
      gonadotrophin response patterns during the beginning stages of puberty overlapped
      between Tanner I and Tanner II, and the cut-offs of basal and stimulated LH
      levels to predict progress from Tanner II to Tanner III had low sensitivities for
      the following 6 months.

PMID- 19863574
TI  - A comparison of prognostic classification systems for differentiated thyroid
      carcinoma.
AB  - OBJECTIVE: To identify and compare prognostic classification systems based on
      basic tumour characteristics that were developed and/or validated for
      differentiated thyroid carcinoma (DTC). DESIGN: Retrospective chart study.
      METHODS: Literature was studied using PubMed. Fifteen different prognostic
      classification systems were identified, of which seven were developed or
      validated for DTC patients and were based on basic tumour characteristics. These
      systems were applied to 1225 DTC patients who were treated in our hospital
      between 1978 and 2002. RESULTS: Log-rank analysis of Kaplan-Meier cancer-specific
      survival curves showed that the curve of the Tumor, Lymph-Node, Metastasis (TNM)
      system had the greatest discriminatory power (log-rank test, log P = -84.9). Cox
      regression analysis showed that the TNM system was the most powerful determinant
      of cancer-specific survival curves. Proportion of variance explained (PVE)
      analysis showed that the TNM system had the highest PVE. CONCLUSION: Of the
      prognostic classification systems analysed in this study, the TNM system performs
      best in all the three analyses, and is therefore the most suitable for predicting
      outcome in DTC-patients.

PMID- 19863575
TI  - Elevated calcitonin and procalcitonin levels in nonmedullary benign and malignant
      thyroid nodules.

PMID- 19863576
TI  - Novel sequence variation of AIRE and detection of interferon-omega antibodies in
      early infancy.
AB  - OBJECTIVE: Autoimmune polyendocrine syndrome type I (APS I) is a rare primary
      immunodeficiency disorder characterized by chronic mucocutaneous candidiasis,
      multi-organ autoimmunity and ectodermal dysplasia. Autoantibodies to parathyroid
      and adrenal glands and type I interferons (IFN) are hallmarks of APS I, which
      results from mutations in the autoimmune regulator (AIRE) gene. We wished to
      study clinical, immunological and genetic features of APS I in Hungarian
      patients, and to correlate anti-IFN-omega serum concentration with APS I and
      other multi-organ autoimmune diseases. DESIGN: Detailed analysis of patients with
      APS I and multi-organ autoimmune diseases. PATIENTS: Seven patients with APS I
      and 11 patients with multi-organ autoimmune diseases were studied. MEASUREMENTS:
      Mutational analysis was performed by bidirectional sequencing of AIRE. Antibodies
      against IFN-omega and endocrine organ-specific autoantigens were studied with
      radioimmunoassay. RFLP was performed by digestion of DNA with Hin6I restriction
      enzyme. RESULTS: AIRE sequence analysis revealed homozygous c.769C>T mutations in
      three patients and compound heterozygous sequence variants
      (c.769C>T/c.44_66dup26bp; c.769C>T/c.965_977del13bp; c.769C>T/c.1344delC) in four
      patients with APS I. All the six live patients tested had markedly elevated IFN
      omega antibodies, which were not found in heterozygous siblings or parents. One
      of the identified patients was negative for antibodies against IFN-omega at 6
      weeks of age, but became positive at 7 months. At age 1, he is still without
      symptoms of the disease. In contrast to patients with APS I, no AIRE mutation or
      elevation of IFN-omega antibodies were detected in patients with multi-organ
      autoimmune diseases. CONCLUSION: This is the first overview of patients diagnosed
      with APS I in Hungary. A novel c.1344delC mutation in AIRE was detected. Anti-IFN
      omega antibodies seem to appear very early in life and are helpful to
      differentiate APS I from other multi-organ autoimmune diseases.

PMID- 19863577
TI  - Exaggerated adrenarche in a cohort of Scottish children: clinical features and
      biochemistry.
AB  - OBJECTIVE: To investigate the reported association between exaggerated adrenarche
      (EA) and reduced foetal growth and to identify possible risk factors for future
      morbidity in Scottish children with clinical features of EA. DESIGN: Three-year
      prospective study. MEASUREMENTS: Auxology, blood pressure (BP), biochemical
      analysis of blood and urine, pelvic ultrasound in girls. RESULTS: Fifty-two
      patients were recruited of whom one girl had nonclassical congenital adrenal
      hyperplasia (17-OHP 17 nmol/l) and one had insufficient blood for analysis. The
      final cohort comprised 42 girls of mean (SD) age 7.7 (0.99) and eight boys of 8.8
      (0.67) years. Mean (SD) birth weight was 3.27 (0.49) and 3.10 (0.76) kg in girls
      and boys respectively. Height/weight SDS were 1.13/1.69 in girls and 1.69/1.88 in
      boys. Mean systolic/diastolic BP was 107.8/60.4 (50th-75th centile) in girls and
      115.5/63.9 (75th-91st centile) in boys. Uterine and ovarian development was
      prepubertal. Median serum dehydroepiandrosterone sulphate (DHEAS) was 2.1 and 4.1
      mumol/l, androstenedione 3.1 and 3.8 nmol/l in girls and boys respectively, with
      DHEAS within the reference range/undetectable in 18/2 and androstenedione in 12/6
      patients. Fasting insulin was 9.0 and 15.0 mU/l in girls and boys respectively,
      with concomitant low normal SHBG. Anti-Mullerian hormone (AMH) was 15.7 pmol/l in
      27 girls, compared with 5.0 pmol/l in normal girls aged 5-8 years. CONCLUSIONS:
      Our Scottish EA cohort showed female predominance, no evidence of reduced foetal
      growth, a tendency to overweight with commensurate mild hyperinsulinaemia and
      modest elevation of serum androgens in some patients. We have found raised AMH
      levels in the girls, indicating advanced ovarian follicular development.

PMID- 19863578
TI  - Carisbamate as adjunctive treatment of partial onset seizures in adults in two
      randomized, placebo-controlled trials.
AB  - PURPOSE: To assess the efficacy, safety, and tolerability of the investigational
      drug carisbamate as adjunctive treatment for partial-onset seizures (POS).
      METHODS: Two identical, randomized, placebo-controlled, double-blind studies were
      conducted in adults with POS uncontrolled for >or=1 year. Therapy-refractory
      epilepsy patients (>or=16 years) remained on stable doses of prescribed
      antiepileptic drugs (<or=2) for an 8-week prospective baseline phase and were
      then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or
      placebo, for a 12-week double-blind phase. Primary efficacy end points were
      percent reduction in seizure frequency and responder rate (patients with >or=50%
      reduction in POS frequency) during the double-blind phase compared with the
      prospective baseline phase. RESULTS: Of the 565 patients randomized in study 1,
      93% completed the study; of the 562 randomized in study 2, 94% completed the
      study. Patient characteristics were similar across both studies and treatment
      arms: mean age, 35 years (study 1, range 16-75 years) and 36 years (study 2,
      range 16-74 years); approximately 50% were men. Treatment with carisbamate 400
      mg/day resulted in significant improvement (p < 0.01) in both efficacy measures
      compared with placebo in study 1 but not in study 2. Carisbamate 200 mg/day did
      not differ statistically from placebo in either study. Among the most common
      treatment-emergent adverse events (>or=5% in any group), those with an incidence
      exceeding placebo (>or=3%) were dizziness (400 mg/day group) and somnolence.
      CONCLUSIONS: Carisbamate 400 mg/day was effective in patients with refractory
      partial-onset seizures in one of these global studies. More than 200 mg/day of
      carisbamate is required for efficacy. Carisbamate was well-tolerated in both
      studies.

PMID- 19863579
TI  - Neonatal seizures and long QT syndrome: a cardiocerebral channelopathy?
AB  - We identified a patient with electrophysiologically verified neonatal long QT
      syndrome (LQTS) and neonatal seizures in the presence of a controlled cardiac
      rhythm. To find a cause for this unusual combination of phenotypes, we tested the
      patient for mutations in seven ion channel genes associated with either LQTS or
      benign familial neonatal seizures (BFNS). Comparative genome hybridization (CGH)
      was done to exclude the possibility of a contiguous gene syndrome. No mutations
      were found in the genes (KCNQ2, KCNQ3) associated with BFNS, and CGH was
      negative. A previously described mutation and a known rare variant were found in
      the LQTS-associated genes SCN5A and KCNE2. Both are expressed in the brain, and
      although mutations have not been associated with epilepsy, we propose a
      pathophysiologic mechanism by which the combination of molecular changes may
      cause seizures.

PMID- 19863580
TI  - Antiepileptic drugs combined with high-frequency electrical stimulation in the
      ventral hippocampus modify pilocarpine-induced status epilepticus in rats.
AB  - PURPOSE: To evaluate the effects of high-frequency electrical stimulation (HFS)
      in both ventral hippocampi, alone and combined with a subeffective dose of
      antiepileptic drugs, during the status epilepticus (SE) induced by lithium
      pilocarpine (LP). METHODS: Male Wistar rats, stereotactically implanted in both
      ventral hippocampi, were injected with pilocarpine (30 mg/kg, i.p.) 24 h after
      lithium (3 mEq/kg) administration. One minute following pilocarpine injection,
      HFS (pulses of 60 mus width at 130 Hz at subthreshold intensities and applied
      during 3 h) was applied alone or combined with subeffective doses of
      antiepileptic drugs. RESULTS: HFS alone reduced the incidence of severe
      generalized seizures. This effect was not evident when HFS was combined with
      phenytoin (33.3 mg/kg, i.p.). HFS combined with diazepam (0.41 mg/kg, i.p.) or
      phenobarbital (10 mg/kg, i.p.) reduced the incidence of severe generalized
      seizures and mortality rate, and augmented the latency to first forelimb clonus,
      generalized seizure, and status epilepticus (SE). When combined with gabapentin
      (46 mg/kg, i.p.), HFS reduced the incidence of severe generalized seizures,
      enhanced latency to SE, and decreased mortality rate. DISCUSSION: Subeffective
      doses of antiepileptic drugs that increase the gamma-aminobutyric acid
      (GABA)ergic neurotransmission may represent a therapeutic tool to augment the HFS
      induced anticonvulsant effects.

PMID- 19863581
TI  - Seasonality as a risk factor for sudden unexpected death in epilepsy: a study in
      a large cohort.
AB  - PURPOSE: We attempted to establish whether month and season, or lunar phase, are
      risk factors for sudden unexpected death in epilepsy (SUDEP), as these have all
      been suggested as potential risk factors. METHODS: We used the dataset of the
      National Sentinel Clinical Audit of Epilepsy-Related Death; all death
      certificates of people who died in England and Wales between September 1999 and
      August 2000 and in which epilepsy was mentioned were reviewed. We identified
      people who probably died of SUDEP during that time. We compared the number of
      observed SUDEP cases with those expected according to month of death, season of
      death, minimum external temperature, mean external temperature, and lunar phase.
      RESULTS: Of 2,412 deaths, we identified 409 probable SUDEPs. We found no evidence
      for an association between either mean temperature group or minimum temperature
      group and SUDEP, although there appeared to be a slight excess of sudden deaths
      in the coldest (mean temperature) groups. We also found no association between
      SUDEP and month, season, or lunar phase. DISCUSSION: Some causes of death appear
      to be related to temperature, but we found no convincing evidence to support a
      link between temperatures or seasons and sudden unexpected death in epilepsy. It
      is important to identify risk factors for SUDEP, but it is also important that
      evidence is established before hypotheses are accepted.

PMID- 19863582
TI  - A vertebrate reproductive system involving three ploidy levels: hybrid origin of
      triploids in a contact zone of diploid and tetraploid palearctic green toads
      (Bufo viridis subgroup).
AB  - The rise and consequences of polyploidy in vertebrates, whose origin was
      associated with genome duplications, may be best studied in natural diploid and
      polyploid populations. In a diploid/tetraploid (2n/4n) geographic contact zone of
      Palearctic green toads in northern Kyrgyzstan, we examine 4ns and triploids (3n)
      of unknown genetic composition and origins. Using mitochondrial and nuclear
      sequence, and nuclear microsatellite markers in 84 individuals, we show that 4n
      (Bufo pewzowi) are allopolyploids, with a geographically proximate 2n species (B.
      turanensis) being their maternal ancestor and their paternal ancestor as yet
      unidentified. Local 3n forms arise through hybridization. Adult 3n mature males
      (B. turanensis mtDNA) have 2n mothers and 4n fathers, but seem distinguishable by
      nuclear profiles from partly aneuploid 3n tadpoles (with B. pewzowi mtDNA). These
      observations suggest multiple pathways to the formation of triploids in the
      contact zone, involving both reciprocal origins. To explain the phenomena in the
      system, we favor a hypothesis where 3n males (with B. turanensis mtDNA) backcross
      with 4n and 2n females. Together with previous studies of a separately evolved,
      sexually reproducing 3n lineage, these observations reveal complex reproductive
      interactions among toads of different ploidy levels and multiple pathways to the
      evolution of polyploid lineages.

PMID- 19863583
TI  - When do adaptive plasticity and genetic evolution prevent extinction of a density
      regulated population?
AB  - We study the dynamics of evolutionary recovery after an abrupt environmental
      shift in a density-regulated population with evolving plasticity. Maladaptation
      to the new environment initially causes the population to decline, until adaptive
      phenotypic plasticity and genetic evolution restore positive population growth
      rate. We assume that selection on a quantitative trait is density-independent and
      that the initial cost of plasticity is much lower than the benefit of the initial
      plastic response. The initial partially adaptive plasticity reduces the effective
      magnitude of the environmental shift, whereas evolution of plasticity increases
      the rate of adaptation. Both effects greatly facilitate population persistence.
      In contrast, density dependence of population growth always hinders persistence.
      With theta-logistic population regulation, a lower value of theta produces a
      faster initial population decline and a higher extinction risk.

PMID- 19863584
TI  - The distribution and hypothesis testing of eigenvalues from the canonical
      analysis of the gamma matrix of quadratic and correlational selection gradients.
AB  - Canonical analysis measures nonlinear selection on latent axes from a rotation of
      the gamma matrix (gamma) of quadratic and correlation selection gradients. Here,
      we document that the conventional method of testing eigenvalues (double
      regression) under the null hypothesis of no nonlinear selection is incorrect.
      Through simulation we demonstrate that under the null the expectation of some
      eigenvalues from canonical analysis will be nonzero, which leads to unacceptably
      high type 1 error rates. Using a two-trait example, we prove that the
      expectations for both eigenvalues depend on the sampling variability of the
      estimates in gamma. An appropriate test is to slightly modify the double
      regression method by calculating permutation P-values for the ordered
      eigenvalues, which maintains correct type 1 error rates. Using simulated data of
      nonlinear selection on male guppy ornamentation, we show that the statistical
      power to detect curvature with canonical analysis is higher compared to relying
      on the estimates from gamma alone. We provide a simple R script for permutation
      testing of the eigenvalues to distinguish curvature in the selection surface
      induced by nonlinear selection from curvature induced by random processes.

PMID- 19863585
TI  - Sexual selection, multiple male ornaments, and age- and condition-dependent
      signaling in the common yellowthroat.
AB  - In many animals, sexual selection has resulted in complex signaling systems in
      which males advertise aspects of their phenotypic or genetic quality through
      elaborate ornamentation and display behaviors. Different ornaments might convey
      different information or be directed at different receivers, but they might also
      be redundant signals of quality that function reliably at different times (ages)
      or in different contexts. We explored sexual selection and age- and condition
      dependent signaling in the common yellowthroat (Geothlypis trichas), a sexually
      dichromatic warbler with two prominent plumage ornaments--a melanin-based, black
      facial "mask" and carotenoid-based, UV-yellow "bib." In a three-year study,
      variance among males in the number of social (M(w)) and extra-pair (M(e)) mates
      generated strong sexual selection on mask and bib attributes. Some traits (mask
      size, bib yellow brightness) were correlated with male age and did not experience
      selection beyond age-related increases in M(w) and M(e). Other traits showed age
      specific (bib size) or age-reversed (ultraviolet brightness) patterns of
      selection that paralleled changes in the information-content of each ornament.
      The components of male fitness generating selection in young versus old males
      were distinct, reflecting different sources of variation in male fertilization
      success. Age- and context-dependent changes in the strength, direction, and
      target of selection may help explain the maintenance of multiple ornaments in
      this and other species.

PMID- 19863586
TI  - Evaluation of elevated ploidy and asexual reproduction as alternative
      explanations for geographic parthenogenesis in Eucypris virens ostracods.
AB  - Transitions from sexual to asexual reproduction are often coupled with elevations
      in ploidy. As a consequence, the importance of ploidy per se for the maintenance
      and spread of asexual populations is unclear. To examine the effects of ploidy
      and asexual reproduction as independent determinants of the success of asexual
      lineages, we sampled diploid sexual, diploid asexual, and triploid asexual
      Eucypris virens ostracods across a European wide range. Applying nuclear and
      mitochondrial markers, we found that E. virens consists of genetically highly
      differentiated diploid sexual populations, to the extent that these sexual clades
      could be considered as cryptic species. All sexual populations were found in
      southern Europe and North Africa and we found that both diploid asexual and
      triploid asexual lineages have originated multiple times from several sexual
      lineages. Therefore, the asexual lineages show a wide variety of genetic
      backgrounds and very strong population genetic structure across the wide
      geographic range. Finally, we found that triploid, but not diploid, asexual
      clones dominate habitats in northern Europe. The limited distribution of diploid
      asexual lineages, despite their shared ancestry with triploid asexual lineages,
      strongly suggests that the wider geographic distribution of triploids is due to
      elevated ploidy rather than to asexuality.

PMID- 19863588
TI  - Natural distributions of mitochondrial sequence diversity support new null
      hypotheses.
AB  - A variety of forces and constraints can cause sequence data to deviate from
      patterns predicted under strict neutrality. Here, I present a meta-analysis of
      available aligned sequence data from 12 higher animal taxa to identify whether
      the typical null assumption for an often-used test for neutrality--Tajima's D
      statistic--is an appropriate or useful null given large numbers of empirical
      observations. Across 1068 cytochrome oxidase I (COI) datasets, the mean value for
      Tajima's D is -0.391, with over a sixth of these datasets representing
      "significant" divergence from null assumptions according to this test. These
      results indicate a persistent trend for mitochondrial COI data--chosen for their
      prevalence in population and taxonomic studies--to indicate patterns of diversity
      that deviate from a purely neutral description, and provide compelling support
      for the concept that more complex "null" hypotheses may be necessary in
      population genetics.

PMID- 19863587
TI  - Multiple interacting loci control sex determination in lake Malawi cichlid fish.
AB  - Several models have been proposed to suggest how the evolution of sex-determining
      mechanisms might contribute to speciation. Here, we describe the inheritance of
      sex in 19 fish species from the rapidly evolving flock of cichlids in Lake
      Malawi, Africa. We found that many of these species have a male heterogametic
      (XY) system on linkage group 7. Some species also segregate for a female
      heterogametic (ZW) system on linkage group 5 that is coincident with a dominant
      orange-blotch (OB) color pattern in females. The ZW system is epistatically
      dominant to the XY system when both are segregating within a family. Several
      lines of evidence suggest that additional sex-determining loci are segregating in
      some species. These results are consistent with the idea that genetic conflicts
      play an important role in the evolution of these species flocks and suggest that
      evolution of sex-determining mechanisms has contributed to the radiation of
      cichlid fish in East Africa.

PMID- 19863589
TI  - Evolutionary feedbacks between reproductive mode and mutation rate exacerbate the
      paradox of sex.
AB  - Evolutionary theory suggests that low mutation rates should favor the persistence
      of asexuals. Additionally, given the observation that most nonneutral mutations
      are deleterious, asexuality may strengthen selection for reduced mutation rates.
      This reciprocal relationship raises the possibility of a positive feedback loop
      between sex and mutation rate. We explored the consequences of this evolutionary
      feedback with an individual-based model in which a sexual population is
      continually challenged by the introduction of asexual clones. We found that
      asexuals were more likely to spread in a population when mutation rates were able
      to evolve relative to a model in which mutation rates were held constant. In
      fact, under evolving mutation rates, asexuals were able to spread to fixation
      even when sexuals faced no cost of sex whatsoever. The added success of asexuals
      was the result of their ability to evolve lower mutation rates and thereby slow
      the process of mutation accumulation that otherwise limited their spread. Given
      the existence of ample mutation rate variation in natural populations, our
      findings show that the evolutionary feedback between sex and mutation rate may
      intensify the "paradox of sex," supporting the argument that deleterious mutation
      accumulation alone is likely insufficient to overcome the reproductive advantage
      of asexual competitors in the short term.

PMID- 19863590
TI  - Advice for medical students and practitioners with colour vision deficiency: a
      website resource.

PMID- 19863591
TI  - Plasmid-mediated QnrS2 determinant in an Aeromonas caviae isolate recovered from
      a patient with diarrhoea.
AB  - A qnrS2 gene was identified in an Aeromonas caviae isolate (MICs of
      ciprofloxacin, norfloxacin and ofloxacin >32 mg/L) from a stool sample collected
      from a patient with gastroenteritis. The analysis of the gyrA and parC genes
      revealed amino acid substitutions Ser83-Ile and Ser80-Thr, respectively. In
      addition, five out of 41 nalidixic acid-resistant Aeromonas isolates studied (26
      identified as Aeromonas veronii bv sobria and 15 identified as A. caviae) showed
      ciprofloxacin resistance. The identification of plasmid-mediated qnr genes
      outside of the Enterobacteriaceae underlines a possible diffusion of these
      resistance determinants among Gram-negative rods. This emphasizes the importance
      of monitoring the emergence of these determinants as well as their dissemination
      among the Aeromonadaceae.

PMID- 19863592
TI  - Relationship between arterial baroreflex sensitivity and exercise capacity in
      patients with acute myocardial infarction.
AB  - SUMMARY: To investigate the relationship between arterial baroreflex sensitivity
      (BRS) and exercise capacity, we examined arterial BRS and its relation to
      exercise capacity during upright bicycle exercise in 40 uncomplicated patients
      with acute myocardial infarction. Arterial BRS was measured 3 weeks (20 +/- 5
      days) after acute myocardial infarction and assessed by calculating the
      regression line relating phenylephrine-induced increases in systolic blood
      pressure to the attendant changes in the R-R interval. All patients underwent
      graded symptom-limited bicycle exercise with direct measurements of hemodynamic
      and metabolic measurements. In all patients, the average arterial BRS was 5.6 +/-
      2.6 ms mmHg(-1). There were no significant correlations between arterial BRS and
      hemodynamic measurements at rest. However, arterial BRS was negatively related to
      systemic vascular resistance at peak exercise (r = -0.60, P = 0.0001) and percent
      change increase in systemic vascular resistance from rest to peak exercise (r = 
      0.45, P = 0.003), whereas arterial BRS was positively related to cardiac output
      (r = -0.48, P = 0.002) and stroke volume at peak exercise (r = 0.42, P = 0.007),
      and percent change increase in cardiac output (r = -0.55, P = 0.0002) and stroke
      volume from rest to peak exercise (r = 0.41, P = 0.008). Furthermore, arterial
      BRS had modest but significant correlations with peak oxygen consumption (r = 
      0.48, P = 0.002) and exercise duration (r = 0.35, P = 0.029), indicating that
      patients with better arterial BRS have better exercise capacity in patients with
      acute myocardial infarction. These results suggest that arterial BRS was linked
      to central and peripheral hemodynamic responses to exercise and hence,
      contributed to exercise capacity after acute myocardial infraction.

PMID- 19863593
TI  - Partial splenic embolization and peg-IFN plus RBV in liver transplanted patients
      with hepatitis C recurrence: safety, efficacy and long-term outcome.
AB  - BACKGROUND: There is limited information on the long-term outcome in liver
      transplant (LT) subjects undergoing partial splenic embolization (PSE) prior to
      full dose pegylated interferon/ribavirin (peg-IFN/RBV). METHODS: Retrospective
      review of eight LT subjects after PSE and antiviral therapy. RESULTS: Baseline
      platelets and neutrophils were <50 000 cells/mL and <1000 cells/mL in 75% and
      50%. Mean splenic infarction volume was 85 +/- 13%. PSE produced major
      complications in three (37.5%): recurrent sterile netrophilic ascites and renal
      insufficiency (n = 2), and splenic abscess (n = 1). Full-dose peg-IFN/RBV was
      started in seven (87.5%), with two early withdrawals (28.6%) despite early
      virological response (toxicity and infection); both subjects died. Anemia led to
      RBV dose-adjustment in six (86%), with human recombinant erythropoietin (EPO) use
      in four (57%). No peg-IFN adjustments or granulocyte-colonies stimulating factor
      were needed. Two patients reached sustained virological response (SVR) (28.6%).
      Two non-responders maintained prolonged therapy with biochemical/histological
      improvement. After a median follow-up of 151 wk, we observed significant
      improvements in hematological parameters, aspartate aminotransferase, alanine
      aminotransferase, international normalized ratio, and prothrombin activity.
      CONCLUSIONS: Extensive PSE after LT produced significant morbidity (37.5%). Peg
      IFN/RBV was completed in five out of seven (71%), with SVR in two (28.6%). RBV
      adjustement due to anemia was high despite EPO use. Only patients able to
      complete or maintain antiviral therapy survived, with long-term significant
      benefits in hematological parameters and liver function tests.

PMID- 19863594
TI  - Soft X-ray spectro-tomography study of cyanobacterial biomineral nucleation.
AB  - Quantitative three-dimensional (3D) chemical mapping using angle-scan spectro
      tomography in a scanning transmission (soft) X-ray microscope (STXM) has been
      used for the first time to characterize the early stages of CaCO(3) biomineral
      nucleation on the surface of planktonic freshwater cyanobacterial cells of the
      strain Synechococcus leopoliensis PCC 7942. The apparatus for STXM angle-scan
      tomography is described. Aspects of sample preparation, sample mounting and data
      acquisition and quantitative analysis and interpretation are discussed in detail.
      Angle-scan tomography and chemically selective 3D imaging at multiple photon
      energies has been combined with a complete 2D spectromicroscopic characterization
      of the biochemical and mineralogical composition. This has provided detailed
      insights into the mechanisms of mineral nucleation, leading to development of a
      detailed model of CaCO(3) nucleation by the cyanobacterial strain S. leopoliensis
      PCC 7942. It shows that Ca is absorbed by the extracellular polymeric substances
      (EPS) of the cyanobacteria and that CaCO(3) with aragonite-like short-range order
      is precipitated rather homogeneously within the EPS. The precipitation of the
      thermodynamically more stable calcite polymorph then starts at Ca-rich hot spots
      within the EPS and close to the cyanobacteria.

PMID- 19863595
TI  - Timing of morphological and ecological innovations in the cyanobacteria--a key to
      understanding the rise in atmospheric oxygen.
AB  - When cyanobacteria originated and diversified, and what their ancient traits
      were, remain critical unresolved problems. Here, we used a phylogenomic approach
      to construct a well-resolved 'core' cyanobacterial tree. The branching positions
      of four lineages (Thermosynechococcus elongatus, Synechococcus elongatus,
      Synechococcus PCC 7335 and Acaryochloris marina) were problematic, probably due
      to long branch attraction artifacts. A consensus genomic tree was used to study
      trait evolution using ancestral state reconstruction (ASR). The early
      cyanobacteria were probably unicellular, freshwater, had small cell diameters,
      and lacked the traits to form thick microbial mats. Relaxed molecular clock
      analyses suggested that early cyanobacterial lineages were restricted to
      freshwater ecosystems until at least 2.4 Ga, before diversifying into coastal
      brackish and marine environments. The resultant increases in niche space and
      nutrient availability, and consequent sedimentation of organic carbon into the
      deep oceans, would have generated large pulses of oxygen into the biosphere,
      possibly explaining why oxygen rose so rapidly. Rapid atmospheric oxidation could
      have destroyed the methane-driven greenhouse with simultaneous drawdown in
      pCO(2), precipitating 'Snowball Earth' conditions. The traits associated with the
      formation of thick, laminated microbial mats (large cell diameters, filamentous
      growth, sheaths, motility and nitrogen fixation) were not seen until after
      diversification of the LPP, SPM and PNT clades, after 2.32 Ga. The appearance of
      these traits overlaps with a global carbon isotopic excursion between 2.2 and 2.1
      Ga. Thus, a massive re-ordering of biogeochemical cycles caused by the appearance
      of complex laminated microbial communities in marine environments may have caused
      this excursion. Finally, we show that ASR may provide an explanation for why
      cyanobacterial microfossils have not been observed until after 2.0 Ga, and make
      suggestions for how future paleobiological searches for early cyanobacteria might
      proceed. In summary, key evolutionary events in the microbial world may have
      triggered some of the key geologic upheavals on the Paleoproterozoic Earth.

PMID- 19863596
TI  - Supralevator fistula-in-ano in tuberculosis.
AB  - AIM: Perianal Mycobacterium tuberculosis is rare, but tuberculosis (TB) is now
      endemic in many areas of the world. It is essential to recognize TB to institute
      appropriate management. We report three cases of TB presenting with supralevator
      abscess. METHOD: We analysed the outcomes of three patients who presented to our
      unit, from 2004 to 2009, with supralevator abscess caused by TB. RESULTS: The
      patients presented as emergencies with symptoms of per-anal sepsis. All required
      multiple drainage procedures. Supralevator extension was confirmed clinically and
      radiologically (by magnetic resonance imaging in two patients and by computed
      tomography scanning in one patient). One patient was diagnosed by perianal
      biopsy, the second by culture of pus and the third by sputum culture. Following
      drainage, all three patients were given anti-TB medication for 6 months. In all
      patients, the fistulae had high communication with the anal canal. In one
      patient, local drainage and medical therapy led to sepsis resolution, the second
      patient has residual complex fistulae and the third patient has recently
      commenced antimicrobial therapy. CONCLUSION: As TB is endemic in many parts of
      Europe, TB should be suspected in patients with complex and/or recurrent perianal
      sepsis. Samples for histological and bacteriological analyses should be obtained
      from these patients. Recurrent perianal drainage procedures are likely to be
      required, and sepsis may persist after anti-TB therapy.

PMID- 19863597
TI  - Faecal diversion in the management of perianal Crohn's disease.
AB  - AIM: Severe perianal Crohn's disease remains an uncommon but important indication
      for faecal diversion (FD). The advent of biological therapy such as infliximab
      for Crohn's disease is considered to have improved the outcome for these
      patients. The aim of this study was to assess the outcome of patients undergoing
      FD for perianal Crohn's disease and the impact of biological therapy
      (infliximab). METHOD: Retrospective chart review was undertaken of patients who
      underwent FD for management of perianal Crohn's disease at two tertiary centres
      between 1990 and 2007. Patient demographics, disease extent and use of biological
      therapy were recorded. Subsequent surgery was assessed. The impact of infliximab
      on rates of proctocolectomy and restoration of intestinal continuity was
      assessed. RESULTS: Twenty-one patients (one male, 20 female), median age 34 years
      (range 21-67 years), underwent FD for perianal Crohn's disease. At a median
      follow-up time of 22 months (range 4-121 months), four patients had undergone
      stoma closure, 11 had had proctocolectomy and six had a stoma in situ. The
      effects of the procedure on severity of perianal disease were no effect in four
      (19%), temporary improvement in six (29%), initial improvement with later plateau
      in seven (33%) and healing in four patients (19%). Eleven patients (52%) received
      infliximab. In this group, four underwent proctocolectomy and two had intestinal
      continuity restored. This was not significantly different from the noninfliximab
      group. CONCLUSION: Patients undergoing FD for perianal Crohn's disease have <20%
      likelihood of restoration of intestinal continuity. This is not improved with
      biological therapy.

PMID- 19863598
TI  - Clinical and endoscopic characteristics of acute haemorrhagic rectal ulcer, and
      endoscopic haemostatic treatment: a retrospective study of 95 patients.
AB  - AIM: Acute haemorrhagic rectal ulcer (AHRU) is characterized by sudden onset of
      painless and massive rectal bleeding in elderly bedridden patients who have
      serious illness. Endoscopic diagnosis and management of AHRU is, however, still
      controversial. We retrospectively investigated 95 AHRU patients to elucidate the
      clinical characteristics, endoscopic findings and haemostatic strategies. METHOD:
      Between January 1999 and March 2007, 95 patients were diagnosed with AHRU in our
      hospital. Medical records and colonoscopy files were reviewed. Clinical features,
      colonoscopic findings, haemostatic treatment and outcome of the patients were
      evaluated. RESULTS: Eighty per cent of the patients were bedridden at the onset.
      The most frequent underlying disorder was cerebrovascular disease (36.8%).
      Hypoalbuminaemia (< 3.5 g/dl) was seen in 92.6% of the patients. Endoscopic
      findings of AHRU were classified as circumferential ulcer (41.1%), linear or
      nearly round small ulcer(s) (44.2%), circumferential and small ulcer(s) (7.4%)
      and Dieulafoy-like ulcer (7.4%). Primary endoscopic haemostatic treatment was
      performed in 45.3% of cases. Recurrent bleeding occurred in 24.2% of patients.
      Permanent haemostasis was achieved by secondary endoscopic treatment in 82.6% of
      re-bleeding patients. CONCLUSION: Understanding the typical clinical and
      endoscopic findings and careful endoscopic examination are important for the
      accurate diagnosis of AHRU, and endoscopic haemostatic therapy may be effective
      for bleeding patients.

PMID- 19863599
TI  - Prognostic analysis for carcinoid tumours of the rectum: a single institutional
      analysis of 106 patients.
AB  - AIM: Rectal carcinoid is a rare rectal tumour with a good prognosis. The aim of
      this study was to assess its clinicopathological characteristics and prognostic
      factors in a single institution. METHOD: Clinical and pathological information
      was retrospectively collected in a single institution, and patients' outcomes
      were determined. Multivariate analyses were performed to find independent
      prognostic factors attributed to overall survival. RESULTS: A total of 106
      patients with rectal carcinoid were included. In all, 66% of the patients
      underwent transanal local excision and 34% had transabdominal surgery. The 5-year
      survival rate was 87%. Muscularis invasion was the only independent prognostic
      factor for predicting 5-year survival (P = 0.00046). Tumour size was found to be
      significantly associated with muscular invasion (P = 0.00003). The area under the
      curve of tumour size in the receiver operating characteristic curve for
      predicting muscular invasion was 0.92. CONCLUSION: Patients with rectal carcinoid
      have a good prognosis. Muscular invasion is an independent risk factor of
      survival.

PMID- 19863600
TI  - Folic acid supplementation and colorectal cancer risk: a meta-analysis.
AB  - AIM: This meta-analysis aims to determine the effect of folic acid
      supplementation on colorectal cancer risk. METHOD: A structured search of the
      MEDLINE, EMBASE, Cochrane and CINAHL databases was undertaken in July 2008. All
      published full text English language articles were searched that included a
      randomized or pseudo-randomized comparison of subjects who received folate vs
      subjects who did not in relation to their risk of adenoma or advanced adenomatous
      lesions, including colorectal cancer. A weighted treatment effect (using fixed
      effects) was calculated across trials. RESULTS: Overall, the risk of an
      adenomatous lesion was not increased (odds ratio 1.09, 95% confidence interval
      0.93-1.28) among patients who received folate supplementation for up to 3 years;
      however, for those who received folate for over 3 years, the risk of an
      adenomatous lesion was increased (odds ratio 1.35, 95% confidence interval 1.06
      1.70). The risk associated with treatment was the highest for the occurrence of
      an advanced lesion (odds ratio 1.50, 95% confidence interval 1.06-2.10). There
      was no significant statistical heterogeneity in the analyses. CONCLUSION: At the
      3-year colonoscopic follow up, folate supplementation had no effect on adenoma
      recurrence overall. While colonic surveillance beyond 3 years revealed an
      increased risk of colorectal adenoma, especially advanced adenoma, among those
      participants randomized to the folate group. This meta-analysis challenges the
      results from epidemiological studies that folate status is inversely related to
      the risk of developing colorectal cancer.

PMID- 19863601
TI  - Factors affecting the outcome of temporary sacral nerve stimulation for faecal
      incontinence. The value of the new tined lead electrode.
AB  - AIM: Sacral nerve stimulation (SNS) is an effective but expensive treatment for
      faecal incontinence. About 50% of the patients are unresponsive for unknown
      reasons, hence knowledge of any factors predictive of success would be highly
      desirable. The aim of this study was to analyse the potential factors associated
      with a successful outcome of the temporary test of electrostimulation. METHOD:
      Eighty-five patients with faecal incontinence were tested for SNS. The cause was
      idiopathic in 45, iatrogenic or obstetric in 28, spinal lesion or neurological
      diseases in nine and anal malformation in three patients; 43 were tested with a
      unipolar electrode and 42 with a quadripolar electrode. The severity of faecal
      incontinence was evaluated using the American Medical System (AMS) score and
      Wexner's score. RESULTS: A positive response was obtained in 45 patients (53%);
      40 (47%) were implanted with a permanent pulse generator. Responders and
      nonresponders were comparable in age, duration of incontinence, anal manometry,
      pudendal nerve terminal motor latency and diabetes. Unipolar electrode test (PNE
      test) was able to elicit positive responses in 18 of 43 (42%) and the quadripolar
      in 27 of 42 patients (P < 0.001). Type of incontinence and gender did not affect
      the success rate. Patients with idiopathic incontinence had a significantly
      higher response rate (P =0.022). Multivariate regression analysis indicated use
      of a quadripolar electrode as the only independent variable predicting the
      success of SNS (OR = 5.58, P = 0.009). CONCLUSION: Use of the quadripolar
      electrode is the only factor significantly related to the success of SNS.

PMID- 19863602
TI  - Management of idiopathic anal fistula using cross-linked collagen: a prospective
      phase 1 study.
AB  - AIM: Fibrin glue and porcine intestinal submucosa are used in novel sphincter
      preserving techniques to heal anal fistulae. However, their success is highly
      variable and decreases with the length of follow up. The aim of this study was to
      assess the safety, feasibility and potential efficacy of another novel agent,
      cross-linked collagen, in two different physical formats, to heal anal fistulae.
      METHOD: Prospectively recruited patients underwent symptom, continence and anal
      physiology assessments and magnetic resonance imaging. Patients with secondary
      tracts or acute sepsis were excluded. At operation, participants were randomized
      to receiving a solid collagen implant or collagen fibres suspended in fibrin
      glue. Follow up included repeat symptom, continence and physiological assessments
      at 3 months, and regular clinical review thereafter. RESULTS: Twenty-nine of 43
      entrants were eligible for inclusion. Thirteen patients received the collagen
      implant, and 16 collagen-fibrin glue. Three months postoperation, no patient
      experienced acute sepsis or continence disturbance, and sphincter function and
      integrity were unchanged. At 29 months, 12 of 15 (one lost to follow up) patients
      treated with collagen-fibrin glue were healed, compared with seven of 13 who
      received the implant. CONCLUSION: In the short-to-medium term, both techniques
      are safe and equally effective. The results justify continued research into the
      use of biomaterials to heal anal fistulae.

PMID- 19863603
TI  - Rectal perforation and peritonitis complicating stapled haemorrhoidopexy.

PMID- 19863604
TI  - Drainage of a pelvic collection with the Heald Silastic Anal Stent.
AB  - The Heald Silastic Anal Stent (HSAS) was designed to protect a newly constructed
      low colorectal anastomosis by keeping the anus open for up to 10 days
      postoperatively, and has also been used in combination with percutaneous drainage
      to treat a leak from a low rectal anastomosis. We describe a technique in two
      patients where the HSAS alone allowed adequate drainage of a leaking low
      colorectal anastomosis.

PMID- 19863605
TI  - A colourachocutaneous fistula.

PMID- 19863607
TI  - Association between interleukin-4R and TGF-beta1 gene polymorphisms and the risk
      of colorectal cancer in a Korean population.
AB  - AIM: Colorectal cancer is associated with inflammatory bowel disease. The
      mechanisms of how different genetic make-ups of cytokines might influence the
      individual susceptibility to develop particular types of tumours are still
      unknown. The authors analysed the association between genetic polymorphisms in
      cytokine/cytokine receptor genes and the risk of colorectal cancer in a Korean
      population. METHOD: The authors assessed polymorphisms of the interleukin: IL-1,
      IL-1R, IL-2, IL-4, IL-4R, IL-10, transforming growth factor (TGF)-beta1, IFN
      gamma genes in Korean patients with colorectal cancer (n = 170) and in a normal
      healthy control group (n = 130) to investigate the association between theses
      cytokine gene polymorphisms and the risk of colorectal cancer. RESULTS: The IL-4R
      1902*T allele was found to be associated with an increased risk of colon cancer
      (P < 0.01, OR = 2.0) and rectal cancer (P < 0.05, OR = 1.8). The IL-4R 1902*C
      allele was associated with a decreased risk of both colon cancer (P < 0.01, OR =
      0.51) and rectal cancer (P < 0.05, OR = 0.5). The TFG-beta1 10*T allele was found
      to be associated with an increased risk of colon cancer (P < 0.00, OR = 2.3) and
      the TFG-beta1 10*C allele with a decreased risk of colon cancer (P < 0.00, OR =
      0.43). CONCLUSION: These results suggest that the genetic polymorphisms of IL-4R
      and TGF-beta1 are associated with the risk of colorectal cancer in a Korean
      population.

PMID- 19863608
TI  - -509C>T polymorphism in the TGF-beta1 gene promoter is not associated with
      susceptibility to and progression of colorectal cancer in Chinese.
AB  - AIM: Colorectal cancer is common, accounting for nearly 10% of all cancers.
      Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine that has
      been implicated in the pathogenesis of colorectal neoplasia. The most studied 
      509C>T polymorphism of TGF-beta1 gene has been associated with various kinds of
      cancer. This study investigated the association between this genetic variant and
      the risk and/or progression of colorectal cancer. METHOD: A case-control study
      was carried out of 150 colorectal cancer cases and 503 healthy controls. DNA was
      extracted from blood cell nuclear materials, and -509C>T polymorphism in the TGF
      beta1 gene promoter was genotyped by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). Colorectal cancer tissues (n = 70) were
      obtained from the studied cases for measurement of TGF-beta1 mRNA expression
      levels. We also assessed the plasma TGF-beta1 levels of cases (n = 88) and
      healthy subjects (n = 120). RESULTS: The TGF-beta1 producer genotype, -509TT, was
      not associated with an increased risk of colorectal cancer compared with other
      genotypes. Colorectal cancer patients especially those with a more aggressive
      disease behaviour were more frequently associated with C allele. CONCLUSION: The
      results suggest that TGF-beta1 -509C>T polymorphism is not associated with either
      an increased risk or progression of colorectal cancer.

PMID- 19863609
TI  - The indication and surgical results of local excision following radiotherapy for
      low rectal cancer.
AB  - AIM: Radical surgery of rectal cancer is associated with significant morbidity,
      and some patients with low-lying lesions must accept a permanent colostomy. The
      objective of this study was to evaluate the outcome of local excision followed by
      adjuvant radiotherapy for rectal cancer for curative purposes. METHOD: One
      hundred and seven patients with rectal carcinoma performed with local excision
      were analysed retrospectively. RESULTS: The procedures of local excision were
      trans-anal resection in 83 patients, trans-sacral resection in 16, trans
      sphincteric local resection in five, and trans-vaginal resection in three. The
      overall disease-free survival rate was 80.4% (86/107), including 90.0% (54/60)
      for T1 and 72.3% (34/47) for T2 tumours, respectively. Eighty-two of 107 patients
      underwent adjuvant postoperative radiotherapy after local excision, and 25 did
      not, and the DFS rates between radiation and nonradiation group were
      significantly different for T2 [81.6% (31/38) vs 33.3% (3/9), P < 0.05], but not
      for T1 tumours (90.9%vs 87.5%, P > 0.05). The rates of local recurrence and
      distant metastasis were 13.1% (14/107) and 4.7% (5/106), respectively, and the
      median time to relapse was 15 months (range: 10-53) for local recurrence and 30
      months (21-65) for distant recurrence. The risk factors for local recurrence were
      large tumour (>=3 cm), poorly differentiated adenocarcinoma and T2 tumour.
      CONCLUSIONS: Local excision followed adjuvant radiotherapy is an alternative and
      feasible technique for small T1 rectal cancer in selected cases.

PMID- 19863610
TI  - Surgical care - how can new evidence be applied to clinical practice?

PMID- 19863611
TI  - Individualized magnetic resonance imaging-based neoadjuvant chemoradiation for
      middle and lower rectal carcinoma.
AB  - AIM: In most institutions neoadjuvant chemoradiation for middle and lower rectal
      carcinoma is currently given to patients with tumours of clinical stages II or
      III (cT3,4 and/or N1,2). The possibility of a reduction in the use of neoadjuvant
      chemoradiation by an individualized magnetic resonance imaging (MRI)-based
      indication for neoadjuvant chemoradiation was analysed. METHOD: Assessment of the
      pathological and oncological principles indicating for neoadjuvant treatment was
      used to determine the prognostic importance of the distance between the tumour
      and the circumferential resection margin and pretherapeutic assessment using
      modern MRI. RESULTS: Based on the results of pretreatment MRI scanning, a
      proposal is presented for the treatment of middle and lower rectal carcinoma with
      neoadjuvant chemoradiation. Adopting this proposal, the frequency of neoadjuvant
      chemoradiation decreased from 70% to 35% and the early and late adverse effects
      of this therapy were reduced. In contrast, the expected locoregional recurrence
      rate increased from 6% to 11% if all quality criteria were met and to 18% if not.
      CONCLUSION: An MRI-based indication for neoadjuvant chemoradiation is justified
      only for centres with regular quality assurance of MRI, surgery, radiotherapy and
      pathology. The proposal needs confirmation by long-term follow up and by
      prospective studies with larger numbers of patients.

PMID- 19863612
TI  - The stapled resection of a full-thickness external prolapse: response to Romano
      et al.

PMID- 19863614
TI  - Iodamoeba butschlii in a routine cervical smear.

PMID- 19863613
TI  - A single amino acid defines cross-species reactivity of tree shrew (Tupaia
      belangeri) CD1d to human invariant natural killer T (iNKT) cells.
AB  - The non-classical major histocompatibility complex (MHC) class I molecule CD1d
      presents lipid antigens to invariant natural killer T (iNKT) cells, which are an
      important part of the innate immune system. CD1d/iNKT systems are highly
      conserved in evolution, and cross-species reactivity has been suggested to be a
      common feature of different animals based on research in humans and mice.
      However, we found that CD1d from the tree shrew (Tupaia belangeri), a close
      evolutionary relative of primates, failed to stimulate human iNKT cells, despite
      being more homologous to human CD1d than that of mouse. Sequence comparison and
      molecular modelling showed that two of the key amino acid residues in human CD1d
      proposed to be in direct contact with T-cell receptors were mutated in tree shrew
      CD1d. Substitution of one of the residues, but not the other, with the human
      residue enabled tree shrew CD1d to regain the ability to present lipid antigen to
      human iNKT cells. These results indicate that CD1d/iNKT recognition is species
      specific, and that cross-species reactivity may be less common than currently
      proposed. Also, a naturally occurring CD1d mutation(s) that confers inability to
      stimulate iNKT cell function may have implications for future studies on
      CD1d/iNKT-associated diseases.

PMID- 19863615
TI  - EMMPRIN (CD147) expression and differentiation of papillary thyroid carcinoma:
      implications for immunocytochemistry in FNA cytology.
AB  - OBJECTIVE: Extracellular matrix metalloproteinase inducer (EMMPRIN) and its
      induced matrix metalloproteinases (MMPs) play a crucial role in tumour
      progression, invasion and metastasis. EMMPRIN expression has been demonstrated in
      several tumours, but its expression profile in thyroid cancer remains unclear.
      METHODS: We evaluated the expression profile of EMMPRIN at various stages of
      differentiation of thyroid carcinoma, including 20 cases of well-differentiated
      papillary carcinoma (WDPC), 15 cases of papillary carcinoma with a poorly
      differentiated carcinoma component (PC/PDC) and four cases with an
      undifferentiated carcinoma (UDC) component, using paraffin-embedded sections for
      immunohistochemical stains. Also, we used 32 fine needle aspiration cytology and
      imprint smears from the same cases for immunocytochemical stains. The staining
      results were evaluated with a scoring system. RESULTS: Immunohistochemical
      staining showed that EMMPRIN expression was absent or weak in almost all WDPC
      specimens, whereas it was moderate or strong in PDC and UDC components. In
      tumours that showed a gradual morphological transformation from WDPC to PDC
      components, the expression of EMMPRIN was progressively stronger from the areas
      of WDPC to those of PDC. WDPC, PC/PDC and UDC had expression scores of 4.9, 45.0
      and 245.7, respectively. Results of immunocytochemical staining showed almost the
      same staining profile as those of immunohistochemical staining. The cytological
      atypia of EMMPRIN-positive cells was greater than that of negative cells.
      CONCLUSION: These results indicated that EMMPRIN expression correlates
      significantly with the degree of dedifferentiation of thyroid carcinoma. This
      study demonstrates the feasibility of expression of EMMPRIN using fine needle
      aspiration samples. Therefore, immunocytochemical analysis of EMMPRIN may be a
      novel aid to evaluate the differentiation of thyroid carcinoma.

PMID- 19863616
TI  - KIT expression in postradiation sarcoma.

PMID- 19863617
TI  - Utility of liquid-based cytology in endometrial pathology: diagnosis of
      endometrial carcinoma.
AB  - OBJECTIVE: The purpose of this study was to examine the utility of SurePath
      liquid-based cytology (LBC) compared to conventional cytological preparations
      (CCP) in the identification of endometrial carcinoma. METHODS: During a 13-month
      period, direct endometrial samples were collected from 120 patients using the
      Uterobrush. The material comprised 30 cases each of endometrial carcinoma,
      proliferative endometrium, secretory endometrium and atrophic endometrium. The
      following points were investigated:(i) the frequency of cell clumps in
      endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei.
      RESULTS: (i) Comparison of the frequency of cell clumps with irregular protrusion
      pattern and papillo-tubular pattern showed no statistically significant
      difference in either type of cell clump between CCP and LBC. (ii) Comparison of
      the nuclear area of cells showed a sequential decrease from endometrial carcinoma
      to secretory endometrium, to proliferative endometrium and to atrophic
      endometrium, which was significant in CCP and LBC. (iii) Nuclear area was
      significantly lower with LBC compared with CCP in endometrial carcinoma,
      secretory endometrium and proliferative endometrium but not atrophic endometrium.
      (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease
      from endometrial carcinoma to proliferative endometrium, to secretory endometrium
      and to atrophic endometrium, which was significant in both CCP and LBC. (v)
      Comparison of the degree of overlapping nuclei between CCP and LBC showed no
      significant difference for normal types of endometrium, but LBC had significantly
      higher values (P < 0.0001) in endometrial carcinoma than in CCP. CONCLUSIONS: The
      results of this study revealed that applying diagnostic criteria used in CCP to
      LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation
      and cells were well presented. Although we have not examined all cytological
      features of malignancy and have not considered atypical hyperplasia, we believe
      that this method may be a useful tool in the diagnosis of endometrial cytology.

PMID- 19863618
TI  - Implementing the number needed to harm in clinical practice: risk of myocardial
      infarction in HIV-1-infected patients treated with abacavir.
AB  - OBJECTIVES: The D:A:D study group reported a 1.9-fold increased relative risk
      (RR) of myocardial infarction (MI) associated with current or recent use of
      abacavir. The number needed to harm (NNH) incorporates information about the
      underlying risk of MI and the increased RR of MI in patients taking abacavir.
      METHODS: NNH was calculated as the reciprocal of the difference between the
      underlying risks of MI with and without abacavir use. A parametric statistical
      model was used to calculate the underlying risk of MI over 5 years. RESULTS: The
      relationship between NNH and underlying risk of MI is reciprocal, resulting in
      wide variation in the NNH with small changes in underlying risk of MI. The
      smallest changes in NNH are in the medium- and high-risk groups of MI. The NNH
      changes as risk components are modified; for example, for a patient who smokes
      and has a systolic blood pressure (sBP) of 160 mmHg and a 5-year risk of MI of
      1.3% the NNH is 85, but the NNH increases to 277 if the patient is a nonsmoker
      and to 370 if sBP is within the normal range (120 mmHg). CONCLUSIONS: We have
      illustrated that the impact of abacavir use on risk of MI varies according to the
      underlying risk and it may be possible to increase considerably the NNH by
      decreasing the underlying risk of MI using standard of care interventions, such
      as smoking cessation or control of hypertension.

PMID- 19863619
TI  - Steady-state amprenavir and tenofovir pharmacokinetics after coadministration of
      unboosted or ritonavir-boosted fosamprenavir with tenofovir disoproxil fumarate
      in healthy volunteers.
AB  - Objective An open-label, three-period pharmacokinetic study was conducted to
      investigate the drug interaction potential between fosamprenavir (FPV) and
      tenofovir disoproxil fumarate (TDF). Methods Thirty-six healthy subjects received
      TDF 300 mg once daily (qd) for 7 days (period 1), and then were randomized to 14
      days of either FPV 1400 mg twice daily (bid) or FPV/ritonavir (RTV) 700/100 mg
      bid alone or with TDF (period 2). Subjects continued their randomized dose of FPV
      for 14 more days, adding or removing TDF based upon its receipt in period 2
      (period 3). Twenty-four-hour pharmacokinetic sampling was carried out on day 7 of
      period 1 and on day 14 of periods 2 and 3. Steady-state plasma amprenavir (APV)
      and tenofovir (TFV) pharmacokinetics were assessed by noncompartmental analysis
      and parameter values observed with each regimen were compared using geometric
      mean ratios with 90% confidence intervals. Results After TDF coadministration,
      APV geometric mean minimum concentration (C(min)), maximum concentration
      (C(max)), and area under the plasma concentration-time curve (AUC) increased by
      31, 3 and 7% above values observed with unboosted FPV alone; they also increased
      by 31, 4 and 16% above values observed with FPV/RTV alone. TFV C(min), C(max) and
      AUC decreased by 12, 25 and 15% after FPV coadministration and by 9, 18 and 7%
      after FPV/RTV coadministration. No significant changes in RTV pharmacokinetics
      were observed. No differences were noted in adverse events among dosing periods.
      Conclusions In this evaluation of the interaction between FPV and TDF, increases
      in APV exposures and modest decreases in TFV exposures were observed. These were
      unlikely to be clinically significant.

PMID- 19863620
TI  - Trends in uptake of recently approved antiretrovirals within a national
      healthcare system.
AB  - OBJECTIVE: The aim of the study was to describe Veterans Healthcare
      Administration (VHA) system-wide uptake of three HIV protease inhibitors:
      atazanavir, darunavir and tipranavir. METHODS: This retrospective cohort study
      evaluated VHA uptake of three target antiretrovirals and lopinavir/ritonavir in
      each complete 90-day quarter since approval to December 2007 using VHA HIV
      Clinical Case Registry data. We assessed uptake using number of new
      prescriptions, number of providers and facilities prescribing target agents,
      provider type, clinic type, facility size and location within four US regions.
      RESULTS: Overall, 6551 HIV-infected veterans received target antiretrovirals.
      Uptake was generally greatest within the first year after Food and Drug
      Administration (FDA) approval, and then slightly declined and plateaued.
      Geographically, early adoption of new antiretroviral drugs tended to occur in the
      Western USA, as evidenced by comparison of uptake patterns of new antiretrovirals
      to use of all antiretroviral agents. A small percentage of prescribers of all
      antiretrovirals were responsible for new prescriptions for target medications,
      particularly for darunavir and tipranavir. Providers at almost 50% of VHA
      facilities were prescribing these agents within the first year. CONCLUSIONS:
      Uptake of new antiretrovirals in the VHA generally reflected overall prescribing
      of all antiretrovirals, suggesting a lack of VHA impediments to new
      antiretrovirals in the healthcare system. Some regional variation in uptake among
      the targeted antiretrovirals occurred over time but tended to resolve after the
      first several months. Providers responsible for early prescribing of the target
      medications were limited to a fraction of providers who tended to be physicians
      who practised in infectious disease (ID) clinics at medium-sized facilities.

PMID- 19863622
TI  - Applicability of blunt renal trauma classification of Japanese Association for
      the Surgery of Trauma (JAST).
AB  - OBJECTIVES: The Japanese Association for the Surgery of Trauma (JAST)
      classification is widely applied to select strategies in the treatment of blunt
      renal trauma in Japan. We retrospectively investigated the applicability of the
      JAST classification. METHODS: The JAST classification comprises type I
      (subcapsular), type II (superficial), type III (deep) and pedicle vessel traumas.
      According to these criteria, we reviewed 70 patients with blunt renal trauma
      (types I, II, III and PV; n = 23, 22, 22 and 3, respectively) who were admitted
      to our institution between 1991 and 2007. RESULTS: All patients with type I
      trauma were managed conservatively and three patients with PV trauma underwent
      nephrectomy. Whereas two patients with underlying acquired cystic disease of the
      kidney underwent nephrectomy among type II trauma, the other patients were
      treated conservatively. As four patients with type III trauma underwent
      nephrectomy, injury type subclass and hemorrhage severity were significant
      prognostic factors indicating the need for nephrectomy in this group. Since we
      introduced transcatheter arterial embolization in 1999, none of our patients have
      needed nephrectomy due to a hemorrhage, but one patient underwent nephrectomy
      because of persistent urine leakage. CONCLUSION: Injury type and the hemorrhage
      severity are useful for determining treatment strategy. After the introduction of
      transcatheter arterial embolization, the proportion of nephrectomies due to
      exsanguination decreased and urine leakage also seems to be more important as a
      prognostic factor.

PMID- 19863623
TI  - Editorial Comment to applicability of blunt renal trauma classification of
      Japanese Association for the Surgery of Trauma (JAST).

PMID- 19863624
TI  - Transrectal high-intensity focused ultrasound for the treatment of localized
      prostate cancer: eight-year experience.
AB  - OBJECTIVE: To report on the long-term results of high-intensity focused
      ultrasound in the treatment of localized prostate cancer. METHODS: A total of 517
      men with stage T1c-T3N0M0 prostate cancer treated with Sonablate devices (Focus
      Surgery, Indianapolis, IN, USA) between January 1999 and December 2007 were
      included in the study. Biochemical failure was defined according to the Phoenix
      definition (prostate-specific antigen nadir + 2 ng/mL). results: The median
      follow-up period for all patients was 24.0 months (range, 2 to 88). The
      biochemical disease-free rate (BDFR) in all patients at 5 years was 72%. The BDFR
      in patients with stage T1c, T2a, T2b, T2c and T3 groups at 5 years were 74%, 79%,
      72%, 24% and 33%, respectively (P < 0.0001). BDFR in patients in the low,
      intermediate and high-risk groups at 5 years were 84%, 64% and 45%, respectively
      (P < 0.0001). The BDFR in patients treated with or without neoadjuvant hormonal
      therapy at 7 years were 73% and 53% (P < 0.0001), respectively. In multivariate
      analysis, pretreatment prostate-specific antigen levels (hazard ratio 1.060; P <
      0.0001; 95% confidence interval 1.040-1.080), neoadjuvant hormonal therapy
      (hazard ratio 2.252; P < 0.0001; 95% confidence interval 1.530-3.315) and stage
      (P = 0.0189) were demonstrated to be statistically significant variables.
      Postoperative erectile dysfunction was noted in 33 out of 114 (28.9%) patients
      who were preoperatively potent. CONCLUSIONS: High-intensity focused ultrasound
      therapy appears to be minimally invasive, efficacious and safe for patients with
      localized prostate cancer, particularly those with low- and intermediate-risk
      cancer.

PMID- 19863625
TI  - Brain metastases from testicular germ cell tumors: a retrospective analysis.
AB  - OBJECTIVES: To review our series of testicular germ cell tumors with brain
      metastases and to establish an optimal treatment strategy for them. METHODS:
      Twenty-seven cases of testicular germ cell tumors from three institutions were
      retrospectively reviewed. RESULTS: Twenty-six were non-seminomatous tumors and
      only one was a seminoma. Based on the International Germ Cell Consensus
      Classification, two cases were classified as good prognosis, seven as
      intermediate prognosis and 18 as poor prognosis. Chemotherapy was carried out in
      all patients. Additionally, whole-brain radiotherapy was performed in 10 cases,
      stereotactic radiosurgery in six, whole-brain radiotherapy combined with
      stereotactic radiosurgery in three and complete surgical resection in five. Three
      patients received chemotherapy only. Cancer-specific 5- and 10-year survival
      rates were both 35.9%. The prognosis of those with brain metastases at the time
      of diagnosis tended to be better than those developing brain metastases during
      treatment. Those with a single brain metastasis showed significantly better
      survival than those with multiple brain metastases. No other significant
      prognostic factor was found at multivariate analysis. CONCLUSION: Testicular germ
      cell tumors with brain metastases can be managed with the combination of whole
      brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in
      combination with chemotherapy.

PMID- 19863626
TI  - Scrotal nubbins associated with blind-ending spermatic vessels and a normal vas
      deferens on laparoscopy.
AB  - OBJECTIVES: To determine whether a scrotal nubbin is present in children with
      unilateral non-palpable testis when diagnostic laparoscopy demonstrates blind
      ending vessels and a normal vas deferens entering a closed internal ring.
      METHODS: Eighty consecutive patients with a unilateral nonpalpable testis were
      retrospectively reviewed. Patients underwent initial diagnostic laparoscopy, and,
      if needed, subsequent inguinal exploration was performed. On inguinal
      exploration, any testicular remnant or nubbin-like tissue was removed and
      evaluated histologically. Patients with a patent processus vaginalis were
      excluded from this analysis. RESULTS: Overall, 60 of the 80 patients had neither
      an abdominal testis nor a patent processus vaginalis. Of these 60, 34 patients
      had both a vas deferens and spermatic vessels entering a closed internal ring,
      and all of these underwent inguinal exploration. A total of 17 patients had both
      a blind-ending vas deferens and blind-ending spermatic vessels; no inguinal
      exploration was attempted. In nine patients, laparoscopy revealed blind-ending
      vessels with a normal vas deferens entering the closed internal ring. Of these
      nine, six underwent inguinal exploration, and a scrotal nubbins was found in
      three. At histological examination, hemosiderin deposit and calcification were
      seen in the nubbin tissue. No viable germ cell was detected in these specimens.
      CONCLUSIONS: A laparoscopic finding of blind-ending vessels above the closed
      internal ring does not mean intra-abdominal vanished testis, regardless of the
      appearance of the vas deferens.

PMID- 19863627
TI  - Intra-renal adrenal adenoma: a compelling addition to the differential diagnosis
      of renal mass.
AB  - We report a case of an adrenal rest arising in the kidney of a 37-year-old male.
      An incidental 4.5 cm right upper pole mass with a minimal amount of fat was
      discovered on computed tomography scan. Laparoscopic renal exploration and biopsy
      revealed angiomyolipoma on frozen section. However, final pathological analysis
      of the partial nephrectomy specimen revealed intra-renal adrenal adenoma. The
      diagnosis was confirmed by immunohistochemistries and transmission electron
      microscopy. We review the reported literature on intra-renal adrenal adenoma and
      highlight the aspects that raise the index of suspicion for this entity on the
      differential diagnosis of renal masses.

PMID- 19863628
TI  - Diagnosis and localization of infected renal cyst by diffusion-weighted magnetic
      resonance imaging in polycystic kidney disease.

PMID- 19863629
TI  - Primary renal carcinoid tumor with a mucinous cystadenoma element.

PMID- 19863630
TI  - Acute painful neuropathy of the perineum and scrotum following rapid improvement
      of glycemic control in type 1 diabetes.

PMID- 19863631
TI  - Urbanization and the more-individuals hypothesis.
AB  - 1. Urbanization is a landscape process affecting biodiversity world-wide. Despite
      many urban-rural studies of bird assemblages, it is still unclear whether more
      species-rich communities have more individuals, regardless of the level of
      urbanization. The more-individuals hypothesis assumes that species-rich
      communities have larger populations, thus reducing the chance of local
      extinctions. 2. Using newly collated avian distribution data for 1 km(2) grid
      cells across Florence, Italy, we show a significantly positive relationship
      between species richness and assemblage abundance for the whole urban area. This
      richness-abundance relationship persists for the 1 km(2) grid cells with less
      than 50% of urbanized territory, as well as for the remaining grid cells, with no
      significant difference in the slope of the relationship. These results support
      the more-individuals hypothesis as an explanation of patterns in species
      richness, also in human modified and fragmented habitats. 3. However, the
      intercept of the species richness-abundance relationship is significantly lower
      for highly urbanized grid cells. Our study confirms that urban communities have
      lower species richness but counters the common notion that assemblages in densely
      urbanized ecosystems have more individuals. In Florence, highly inhabited areas
      show fewer species and lower assemblage abundance. 4. Urbanized ecosystems are an
      ongoing large-scale natural experiment which can be used to test ecological
      theories empirically.

PMID- 19863632
TI  - Implementation of a multidisciplinary guideline-driven approach to the care of
      the extremely premature infant improved hospital outcomes.
AB  - AIM: To test the hypothesis that implementing guidelines for the standardized
      care of the extremely premature infant (<27 weeks) in the first week of life
      would improve patient outcomes in an all referral NICU. METHODS: Data were
      collected on all infants <27 weeks gestational age and <7 days of age on
      admission cared for using these small baby guidelines (SBG), as well as on all
      age-matched infants admitted the year prior (comparison). RESULTS: Thirty-seven
      patients were cared for utilizing the SBG and 40 patients were in the comparison
      group. There were no differences between the groups in gestational age,
      birthweight or age on admission. There was no difference in survival to discharge
      (73% SBG, 70% comparison). The mean length of stay for survivors was 112 +/- 38
      days SBG and 145 +/- 76 days (p < 0.05) comparison group. Survival without BPD
      was greater in the SBG group (24%) than in the comparison group (9%; p < 0.05),
      and survival without severe IVH was greater in the SBG group (65%) than in the
      comparison group (38%; p < 0.01). CONCLUSIONS: These data demonstrate that
      applying a unified approach to the care of the extremely premature infant in the
      first week of life resulted in a decrease in the length of hospitalization and
      improved patient outcomes.

PMID- 19863633
TI  - Challenges to 21st century paediatrics.

PMID- 19863634
TI  - Three-dimensional visualization of renal artery stenosis by 64-channel multiple
      detector-row computed tomographical angiography: review of two paediatric cases.
AB  - Three-dimensional visualization of renal arteries has recently been established
      by helical contrast-enhanced multiple detector-row computed tomographical
      angiography (MDCTA) in adults. So far, no information is available on its use in
      children. We reported two children with renal artery stenosis detected by 64
      channel MDCTA. The first patient probably had fibromuscular dysplasia and the
      other neurofibromatosis type 1. The technique showed a left renal artery stenosis
      with a small left kidney in the first patient and a right renal artery stenosis
      in the second. CONCLUSION: MDCTA is an accurate and noninvasive imaging
      technique, easily performed in children, and can be used as an alternative
      diagnostic modality in children with suspected renovascular hypertension.

PMID- 19863635
TI  - Laser microdissection as a new tool to investigate site-specific gene expression
      in enteric ganglia of the human intestine.
AB  - BACKGROUND: Myenteric ganglia are key-structures for the control of intestinal
      motility and their mRNA expression profiles might be altered under pathological
      conditions. A drawback of conventional RT-PCR from full-thickness specimens is
      that gene expression analysis is based on heterogeneously composed tissues. To
      overcome this problem, laser microdissection combined with real-time RT-PCR can
      be used to detect and quantify low levels of gene expression in isolated enteric
      ganglia. METHODS: Fresh unfixed full-thickness specimens of sigmoid colon were
      obtained from patients (n = 8) with diseases unrelated to intestinal motility
      disorders. 10 microm cryo-sections were mounted on membrane-coated slides and
      ultra-rapidly stained with toluidine blue. Myenteric ganglia were isolated by
      laser microdissection and catapulting for mRNA isolation. Real-time RT-PCR was
      performed for selected growth factors, neurotransmitter receptors and specific
      cell type markers. KEY RESULTS: Collection of 0.5 mm(2) of ganglionic tissue was
      sufficient to obtain positive RT-PCR results. Collection of 4 mm(2) resulted in
      ct-values allowing a reliable quantitative comparison of gene expression levels.
      mRNA analysis revealed that neurotrophic growth factor, neurotrophin-3, serotonin
      receptor 3A, PGP 9.5 and S100 beta are specifically expressed in myenteric
      ganglia of the human colon. CONCLUSIONS & INFERENCES: Laser microdissection
      combined with real-time RT-PCR is a novel technique to reliably detect and
      quantify site-specific expression of low-abundance mRNAs (e.g. growth factors,
      neurotransmitter receptors) related to the human enteric nervous system. This
      technical approach expands the spectrum of available tools to characterize
      enteric neuropathologies underlying human gastrointestinal motility disorders at
      the molecular biological level.

PMID- 19863636
TI  - The transition between the phenotypes of Prader-Willi syndrome during infancy and
      early childhood.

PMID- 19863637
TI  - Comparative predictive validity of the Harris Infant Neuromotor Test and the
      Alberta Infant Motor Scale.
AB  - AIM: We compared abilities of the Alberta Infant Motor Scale (AIMS) and the
      Harris Infant Neuromotor Test (HINT), during the infant's first year, in
      predicting scores on the Bayley Scales of Infant Development (BSID) at age 2 and
      3 years. METHOD: This prospective study involved 144 infants (71 females, 73
      males), assessed with the HINT and AIMS at 4 to 6.5 and 10 to 12.5 months and
      with the BSID at 2 and 3 years. Inclusion criteria for typical infants (n=58)
      were the following: 38 to 42 weeks' gestation, birthweight at least 2500g, and no
      congenital anomaly, postnatal health concern, nor major prenatal or perinatal
      maternal risk factor. For at-risk infants (n=86), inclusion criteria were any of
      the following: less than 38 weeks' gestation, birthweight less than 2500g,
      maternal age older than 35 years or younger than 19 years at infant birth,
      maternal psychiatric/mental health concerns, prenatal drug/alcohol exposure,
      multiple births, or use of reproductive technology. RESULTS: For the overall
      sample, the early (4-6.5mo) HINT had higher predictive correlations than the AIMS
      for 2-year BSID-II motor outcomes (r=-0.36 vs 0.26), and 3-year BSID-III gross
      motor outcomes (r=-0.45 vs 0.31), as did the 10- to 12.5-month HINT (r=-0.55 vs
      0.47). Correlations were identical for 10- to 12.5-month HINT and AIMS scores and
      3-year BSID-III gross motor (r=-0.58 and 0.58) and fine motor (r=-0.35 and 0.35)
      subscales. When the sample was divided into typical and at-risk groups,
      predictive correlations were consistently stronger for the at-risk infants.
      Categorical predictive analyses were reasonably similar across both tests.
      INTERPRETATION: Results suggest that the HINT has comparable predictive validity
      to the AIMS and should be considered for use in clinical and research settings.

PMID- 19863638
TI  - Outcome of severe unilateral cerebellar hypoplasia.
AB  - AIM: Complete or subtotal absence of one cerebellar hemisphere is exceptional;
      only single cases have been described. We aimed to assess the long-term outcome
      in children with severe unilateral cerebellar hypoplasia (UCH). METHOD: As part
      of a retrospective study we describe neuroimaging features, clinical findings,
      and cognitive outcomes of seven children with UCH (five males, two females; age
      at first magnetic resonance imaging [MRI]: median 1y 3mo, range 9d-8y 10mo; age
      at latest follow-up: median 6y 6mo, range 2y 3mo-14y 11mo). RESULTS: One child
      had abnormalities on prenatal MRI at 21 weeks' gestation. The left cerebellar
      hemisphere was affected in five children, and the right hemisphere in two
      children. The vermis was involved in five children. The volume of the posterior
      fossa was variable. At the latest follow-up, neurological findings included
      truncal ataxia and muscular hypotonia in five children, limb ataxia in three
      patients, and head nodding in two patients. Three children had learning
      disability*, five had speech and language disorders, and one had a severe
      behavioural disorder. INTERPRETATION: Severe UCH is a residual change after a
      disruptive prenatal cerebellar insult, most likely haemorrhagic. The outcome is
      variable, ranging from almost normal development to marked developmental
      impairment. Ataxia is a frequent but not a leading sign. It seems that
      involvement of the cerebellar vermis is often, but not consistently, associated
      with a poorer cognitive outcome, whereas an intact vermis is associated with
      normal outcome and no truncal ataxia.

PMID- 19863639
TI  - Hand movements at 3 months predict later hemiplegia in term infants with neonatal
      cerebral infarction.
AB  - AIM: The aim of this study was to explore the predictive value of quantitative
      assessment of hand movements in 3-month-old infants after neonatal stroke.
      METHOD: Thirteen infants born at term (five females, eight males; mean
      gestational age 39.4wks, SD 1.19, range 37-41wks; mean birthweight 3240g, SD 203,
      range 2900-3570g) with neonatal arterial ischaemic cerebral infarction, and 13
      healthy infants (mean gestational age 39.1wks, range 37-41wks, SD 1.26; mean
      birthweight 3190g, SD 259, range 2680-3490g) were enrolled in the study. The
      absolute frequency and the asymmetry of global hand opening and closing, wrist
      segmental movements, and independent digit movements were assessed from
      videotapes recorded at around 12 weeks. Neurological outcome was assessed when
      the infants were at least 18 months old using Touwen's neurological examination.
      RESULTS: Five of the 13 infants with neonatal stroke had normal neurological
      development, and eight had hemiplegia. Asymmetry of wrist segmental movements and
      the absolute frequency of independent digit movements were significantly
      different between infants with and without hemiplegia (p=0.006 and p=0.008,
      respectively). No differences were found in global hand movements.
      INTERPRETATION: We propose that the observed abnormalities of hand movements are
      the result of two different mechanisms: direct disruption of the corticospinal
      projection to the spinal cord, and altered modulation of the central pattern
      generators of general movements.

PMID- 19863640
TI  - Diagnosis of eosinophilic esophagitis after fundoplication for 'refractory
      reflux': implications for preoperative evaluation.
AB  - A small percentage of patients who carry the diagnosis of refractory
      gastroesophageal reflux disease (GERD) actually have eosinophilic esophagitis
      (EoE). The purpose of this study was to describe a series of patients who
      underwent fundoplication for presumed refractory GERD, but subsequently were
      found to have EoE. We performed a retrospective analysis of our EoE database.
      Patients diagnosed with EoE after Nissen were identified. Cases were defined
      according to recent consensus guidelines. Five patients underwent anti-reflux
      surgery for refractory GERD, but were subsequently diagnosed with EoE. None had
      esophageal biopsies prior to surgery, and in all subjects, symptoms persisted
      afterward, with no evidence of wrap failure. The diagnosis of EoE was typically
      delayed (range: 3-14 years), and when made, there were high levels of esophageal
      eosinophilia (range: 30-170 eos/hpf). A proportion of patients undergoing
      fundoplication for incomplete resolution of GERD symptoms will be undiagnosed
      cases of EoE. Given the rising prevalence of EoE, we recommend obtaining proximal
      and distal esophageal biopsies in such patients prior to performing anti-reflux
      surgery.

PMID- 19863641
TI  - Atypical esophageal vascular lesions observed in liver cirrhosis.
AB  - Chronic liver disease is known to be associated with several vascular alterations
      including portal hypertension and hepato-pulmonary insufficiency. We report a
      case of esophageal vascular lesions resembling spider naevi in a patient with
      nonalcoholic cirrhosis who underwent an upper gastrointestinal (GI) endoscopy. We
      observed the presence of multiple white round elevations, 5-6 mm in size, with
      radiating thin-walled vessels, in the middle and distal esophagus. The
      histological examination documented the presence of multiple dilated blood
      vessels in the mucosal layer of the esophagus, with striking thickening of the
      endothelium wall. There was no evidence of esophagogastric varices, but only of a
      moderate congestive antral gastropathy. To our knowledge, these endoscopic
      esophageal findings have not yet been described in cirrhosis.

PMID- 19863642
TI  - Options in the management of esophageal perforation: analysis over a 12-year
      period.
AB  - Controversies exist about the management of esophageal perforation in order to
      eliminate the septic focus. The aim of this study was to assess the etiology,
      management, and outcome of esophageal perforation over a 12-year period, in order
      to characterize optimal treatment options in this severe disease. Between May
      1996 and May 2008, 44 patients (30 men, 14 women; median age 67 years) with
      esophageal perforation were treated in our department. Etiology, diagnostic
      procedures, time interval between clinical presentation and treatment,
      therapeutic management, and outcome were analyzed retro- or prospectively for
      each patient. Iatrogenic injury was the most frequent cause of esophageal
      perforation (n= 28), followed by spontaneous (n= 9) and traumatic (n= 4)
      esophageal rupture (in three patients, the reasons were not determinable). Eight
      patients (18%) underwent conservative treatment with cessation of oral intake,
      antibiotics, and parenteral nutrition. Twelve (27%) patients received an
      endoscopic stent implantation. Surgical therapy was performed in 24 (55%)
      patients with suturing of the lesion in nine patients, esophagectomy with delayed
      reconstruction in 14 patients, and resection of the distal esophagus and
      gastrectomy in one patient. In case of iatrogenic perforation, conservative or
      interventional therapy was performed each in 50% of the patients; 89% of the
      patients with a Boerhaave syndrome underwent surgery. The hospital mortality rate
      was 6.8% (3 of 44 patients): one patient with an iatrogenic perforation after
      conservative treatment, and two patients after surgery (one with Boerhaave
      syndrome, one with iatrogenic rupture). No death occurred in the 25 patients with
      a diagnostic interval less than 24 hours, whereas the mortality rate in the group
      (n= 16 patients) with a diagnostic interval of more than 24 hours was 19% (P=
      0.053). In three patients, the diagnostic interval was not determinable
      retrospectively. An individualized therapy depending on etiology, diagnostic
      delay, and septic status leads to a low mortality of esophageal perforation.

PMID- 19863643
TI  - Chemoradiotherapy for cancer of the esophagus: contribution of the leucovorin, 5
      fluorouracil bolus, and infusion-cisplatin-radiotherapy schedule starting with
      two neoadjuvant chemotherapy cycles: results from a pilot study.
AB  - To assess feasibility and tolerance of a modification in the usual
      radiochemotherapy regimen for esophageal cancer by using a leucovorin, 5
      fluorouracil bolus, and infusion-cisplatin regimen (six cycles), beginning with
      two cycles of chemotherapy before conventional radiotherapy (50 Gy), 33 patients,
      30 were men, 62.8 +/- 9.5 years, were treated for an esophageal carcinoma (29
      squamous cell), 27 of these were in stage III (based on computed tomography
      scan). Neoadjuvant chemotherapy was well tolerated; concomitant radiochemotherapy
      was associated with severe adverse events mostly hematological in 23 patients.
      Complete response was achieved in 70%; median overall survival was 14 months, and
      2-year survival was 40 +/- 11%. More than one-third of cycles could be performed
      as outpatients. This regimen seems safe and efficient, and could be conducted in
      an outpatient basis.

PMID- 19863644
TI  - Two-dimensional longitudinal strain and strain rate imaging for assessing the
      right ventricular function in patients with mitral stenosis.
AB  - BACKGROUND: Longitudinal two-dimensional strain (L2DS) deformation is a novel
      technique that evaluates global and regional right ventricular (RV) function. The
      aim of the study was to investigate the systolic function of RV by using this
      method in patients with pure mitral stenosis (MS). METHODS: Conventional
      echocardiography and L2DS analysis were performed in 45 MS patients and 21
      healthy controls. For strain analysis apical four-chamber views were obtained and
      by using a software system, peak systolic strain and strain rates were calculated
      off-line in each segment. RESULTS: The mean global longitudinal strain (GLS) of
      the whole RV (-20 + or - 7 vs. -24 + or - 6%, P= 0.02) and mean GLS of the septum
      (-19 + or - 7 vs. -23 + or - 5%, P = 0.03) were significantly reduced in the MS
      patients. Compared with the control group no significant change was determined in
      the mean GLS of the RV free wall (RVFW). While the mean global longitudinal
      strain rates (GLSR) of the entire RV and RVFW were similar between the groups, a
      significant difference in the mean GLSR of the septum (-1.2 + or - 0.4 vs. -1.5 +
      or - 0.3 s(-1), P= 0.005) was determined in the patients with MS. A regional
      analysis demonstrated that MS patients had significantly reduced strain and
      strain rates in the basal and mid-segments of the septum, whereas only lower
      strain values in the basal RVFW. CONCLUSIONS: RV systolic function evaluated by
      L2DS analysis in patients with MS has shown decreased global and segmental
      systolic functions. (ECHOCARDIOGRAPHY 2010;27:525-533).

PMID- 19863646
TI  - Multiple sclerosis survival: a population-based study in Sicily.
AB  - BACKGROUND AND PURPOSE: There are few population-based surveys on multiple
      sclerosis (MS) survival. To investigate MS survival in MS patients recruited
      during surveys conducted in Sicily. METHODS: Multiple sclerosis patients
      identified during previous surveys were randomly matched to two referent subjects
      by residence, year of birth, and gender. Living status was obtained by
      municipality records (end of follow-up June, 30th 2007) and, for the deceased,
      date and causes of death were searched. Kaplan-Meier plots were used to calculate
      differences in mortality between MS patients and referent subjects. MS risks for
      mortality with 95% confidence intervals (CI) were also calculated. RESULTS: We
      included 194 MS patients and 388 matched persons. Thirty MS patients (15.5%) and
      28 referents (7.2%) had died until the end of follow-up. Mean survival from onset
      of the disease to death was 20.6 years. Mean age at death was 55.5 for MS
      patients and 64.8 for the referents. Adjusted Hazard Ratios for mortality in MS
      was 1.81 (95% CI 1.36-2.40). Kaplan-Meier estimates showed a higher mortality
      amongst patients compared to referent subjects (P < 0.001). CONCLUSIONS: The
      present study confirms the higher mortality risk in MS patients with no
      significant gender difference. Causes of death are related to complications of
      high disability and to increasing age.

PMID- 19863647
TI  - Effects of intermittent theta burst stimulation on spasticity in patients with
      multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Spasticity is a common disorder and a major cause of long
      term disability in patients with multiple sclerosis (MS). Our aim was to evaluate
      whether a recently developed repetitive transcranial magnetic stimulation
      protocol, the intermittent theta burst stimulation (iTBS) is effective in
      modulating lower limb spasticity in MS patients. METHODS: Twenty MS patients were
      pseudorandomized to undergo a 2-week daily sessions of real or sham iTBS
      protocol. The H/M amplitude ratio of the Soleus H reflex, a reliable
      neurophysiological index of spinal excitability and the Modified Ashworth Scale
      (MAS) for spasticity were evaluated by blinded raters before and after the
      stimulation protocols. RESULTS: Patients receiving real iTBS showed a significant
      reduction of H/M amplitude ratio and MAS scores 1 week after the stimulation and
      persisting up to 2 weeks after the end of stimulation protocol. There were no
      significant effects for sham stimulation. CONCLUSIONS: These results show that
      iTBS, a safe, non-invasive, well-tolerated and feasible protocol, is a promising
      tool for the treatment of spasticity in MS.

PMID- 19863648
TI  - Diffusion-weighted imaging findings differ between stroke attributable to
      spontaneous cervical artery dissection and patent foramen ovale.
AB  - BACKGROUND AND PURPOSE: Spontaneous cervical arterial dissection and patent
      foramen ovale (PFO) are important causes of stroke in younger patients. We tested
      whether characteristics of cerebral ischaemia visible on diffusion-weighted
      imaging (DWI) aid in differentiating between these two aetiologies. METHODS:
      Diffusion-weighted imaging was performed after a median of 2 days [interquartile
      range (IQR) 1-3 days] in 94 consecutive patients with an acute ischaemic stroke
      caused either by carotid or vertebral artery dissection (n = 33) or PFO (n = 61).
      We compared number, size, location and predefined patterns of DWI lesions between
      both aetiologies. RESULTS: Ninety-three out of 94 patients had acute DWI lesions
      and were included in the analysis. Multiple DWI lesions occurred more frequently
      in patients with dissection (23/33, 70%) than in those with PFO (26/60, 43%, P =
      0.02). Lesions were larger in the dissection group [median diameter of largest
      lesion, 50 mm (IQR 19-68 mm)] than in the PFO group [23 (9-48) mm; P = 0.02]. The
      distribution of lesion patterns differed between the two aetiologies (P < 0.001):
      single, non-territorial infarcts were more frequent in PFO (25/60, 42%) than in
      dissection (2/33, 6%); large territorial infarcts with or without additional
      smaller lesions in the same territory occurred in 20/33 (61%) patients with
      dissection and in 16/60 (27%) patients with PFO. CONCLUSIONS: Diffusion-weighted
      imaging characteristics differ between PFO and dissection, suggesting differences
      in the pathogenesis of brain infarction between these aetiologies. A single non
      territorial infarct seems to favour PFO as stroke aetiology. Whether this or
      other features are distinctive enough to diagnose PFO or dissection in individual
      patients requires further testing.

PMID- 19863649
TI  - The paradox of intracranial hypotension responding well to CSF drainage.

PMID- 19863650
TI  - A nationwide retrospective analysis on the effect of immune therapies in patients
      with chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - BACKGROUND AND PURPOSE: The guidelines for chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) therapy suggest to use immunoglobulins (IVIg) and
      steroid as first-line therapies. Patients who do not respond to one of the two
      drugs should be switched to the other drug. We collected therapeutic outcome data
      in patients followed at 11 centres in order to document the clinical practice in
      Italy. METHODS: Clinical and electrophysiological data of patients with CIDP were
      entered into a central database. The clinical outcome (Rankin Scale) and drug
      side effects (SE) for first- and second-line therapies were recorded. RESULTS: A
      total of 267 patients were included. The percentage of responders (R) to first
      line therapy [steroid or IVIg or plasma exchange (PE)] was 69%; this number
      increased to 81% when patients who switched to different therapies were included.
      Overall, the percentage of R to IVIg was similar to R to steroids (P = 0.07) and
      higher than R to PE (P < 0.001). Of the main therapies, PE frequently caused SE
      (19%), followed by steroids (12.5%) and IVIg (4%). CONCLUSIONS: Switching between
      traditional therapies increases the number of responder patients. IVIg was
      confirmed to be a therapy with low SE.

PMID- 19863651
TI  - Somatosensory function in asymptomatic Parkin-mutation carriers.
AB  - BACKGROUND AND PURPOSE: It is a matter of debate whether somatosensory
      abnormalities in Parkinson's disease (PD) precede or follow PD motor signs and
      whether they are of central or peripheral origin. The sensory sural nerve action
      potential amplitude (SNAP) was previously reported to be reduced in symptomatic
      Parkin-associated PD. The aim of our study was to investigate asymptomatic Parkin
      mutation carriers to elucidate whether putative somatosensory abnormalities
      precede motor symptoms therewith helping to determine the origin of somatosensory
      signs. METHODS: Nine subjects with Parkin-mutations and nine healthy controls
      were examined clinically, with quantitative sensory testing (QST) and
      neurography. RESULTS: There was a higher frequency of cold pain threshold
      abnormalities and hypofunction of Abeta-fibres/central afferent pathways in
      Parkin-mutation carriers compared to controls. Neurography of Parkin-mutation
      carriers did not indicate peripheral neuropathy. CONCLUSIONS: Sensory
      abnormalities of asymptomatic Parkin-mutation carriers as obtained by QST suggest
      impairment of either small and large peripheral pathways or central somatosensory
      processing. In contrast to Parkin-associated PD, asymptomatic Parkin-mutation
      carriers do not show a reduced SNAP.

PMID- 19863652
TI  - Complex regional influence of photoperiod on the nycthemeral functioning of the
      dorsal and median raphe serotoninergic system in the Syrian hamster.
AB  - The Syrian hamster (Mesocricetus auratus) is a widely used species for the study
      of biological clock synchronization and photoperiodism. The serotoninergic system
      arising from the median (MnR) and the dorsal raphe (DR) is a major actor in
      circadian clock synchronization. This serotoninergic system is also associated
      with functions and behaviours influenced by seasonal changes. The aim of the
      present study was to assess the influence of photoperiod on the daily functioning
      of the MnR and DR serotoninergic system. The morphology of both raphe nuclei was
      analysed in hamsters kept under long and short photoperiod by immunocytochemical
      detection of two markers of the serotoninergic system, serotonin and tryptophan
      hydroxylase (TPH, the rate-limiting enzyme of serotonin synthesis). The
      morphological analysis revealed a fairly complex morphological organization of
      the DR and MnR along their caudo-rostral extent. This morphological organisation
      was similar in the two photoperiods. However, quantification of several markers
      of serotonin (5-HT) synthesis in the DR and MnR revealed a time-dependent
      functioning of serotoninergic cells that was locally influenced by photoperiod.
      In particular, the significant daily variations of tph2-mRNA and TPH levels in
      the rostral MnR, and of the 5-HT/5-HIAA (5-hydroxyindoleacetic acid) ratio within
      the suprachiasmatic nuclei, were abolished under short photoperiod. The results
      are discussed with regard to the known physiological role of the serotoninergic
      system on the biological clock.

PMID- 19863653
TI  - Involvement of paraoxonase 1 genetic variants in Alzheimer's disease
      neuropathology.
AB  - Evidence suggests that the genes involved in brain lipid homeostasis are of
      particular relevance for Alzheimer's disease (AD) etiology. Among these genes,
      that encoding paraoxonase 1 (PON1) has gained newfound interest from a public
      health perspective, as recent studies have suggested that PON1 L55M and Q192R
      genetic variants might affect individual susceptibility to environmental events,
      such as exposure to cholinesterase inhibitors. Cholinesterase inhibitor therapy
      being the treatment of choice for patients with mild to moderate AD, we sought to
      answer two main questions: (i) are these genetic variants associated with
      increased AD risk, earlier age of onset/death, or shorter AD duration; and (ii)
      do they affect the neuropathological hallmarks of AD? This genetic study used a
      large cohort of clinical and autopsy-confirmed AD cases and age-matched,
      cognitively intact controls from the Douglas Hospital Brain Bank, Quebec, Canada
      (n = 1066). The evidence presented here suggests multiple gender-specific effects
      of PON1 polymorphisms on AD etiopathology. The L55M Met allele exerts an AD risk
      enhancing effect only in men (P < 0.001), whereas both men and women carrying the
      M55M/Q192Q genotype exhibit increased survival (2.5 years, P < 0.05) and later
      age of onset (1.5 years, P < 0.05). These genetic variants are also individually
      and significantly associated, sometimes in opposite directions for both genders,
      with beta-amyloid levels (P < 0.001), senile plaque accumulation (P < 0.001) and
      choline acetyltransferase activity (P < 0.05) in, respectively, two of two, five
      of six, and three of six brain areas. These results suggest an involvement of the
      PON1 gene in AD etiopathology and responses to treatment.

PMID- 19863654
TI  - Relationship of arousal to circadian anticipatory behavior: ventromedial
      hypothalamus: one node in a hunger-arousal network.
AB  - The mechanisms by which animals adapt to an ever-changing environment have long
      fascinated scientists. Different forces, conveying information regarding various
      aspects of the internal and external environment, interact with each other to
      modulate behavioral arousal. These forces can act in concert or, at times, in
      opposite directions. These signals eventually converge and are integrated to
      influence a common arousal pathway which, depending on all the information
      received from the environment, supports the activation of the most appropriate
      behavioral response. In this review we propose that the ventromedial hypothalamic
      nucleus (VMN) is part of the circuitry that controls food anticipation. It is the
      first nucleus activated when there is a change in the time of food availability,
      silencing of VMN ghrelin receptors decreases food-anticipatory activity (FAA)
      and, although lesions of the VMN do not abolish FAA, parts of the response are
      often altered. In proposing this model it is not our intention to exclude
      parallel, redundant and possibly interacting pathways that may ultimately
      communicate with, or work in concert with, the proposed network, but rather to
      describe the neuroanatomical requirements for this circuit and to illustrate how
      the VMN is strategically placed and connected to mediate this complex behavioral
      adaptation.

PMID- 19863655
TI  - Theoretical and conceptual issues in time-place discrimination.
AB  - The need to discover resources that are available under specific environmental
      constraints represents a fundamental environmental pressure on the evolution of
      behavior. Time-place discrimination refers to the ability to secure resources
      when they are available under specific temporal and spatial contingencies. This
      article reviews a number of examples of time-place discrimination. The review
      highlights theoretical and conceptual issues that are needed to behaviorally
      identify the mechanisms responsible for time-place performance. Next, limitations
      on time-place performance that may be imposed by a circadian system are
      described. Finally, a number of lines of research that broaden these limitations
      are discussed. These lines of research include studies that suggest that (i) a
      broad range of long intervals (outside the limited range of circadian
      entrainment) are timed, (ii) at least some long intervals (16-21 h) are timed
      with an endogenous self-sustaining oscillator, (iii) short intervals (in the
      range of 1-3 min) are timed with an endogenous self-sustaining oscillator, and
      (iv) memory for specific unique events (including when and where they occurred)
      is based on a circadian representation of time. It is concluded that a unified
      theory of timing that can retain the times of occurrence of individual events is
      needed. The time of occurrence of an event may be encoded not only with respect
      to a circadian oscillator but also with respect to other oscillators in the long
      interval and short-interval ranges.

PMID- 19863656
TI  - Timing and anticipation: conceptual and methodological approaches.
AB  - Anticipation occurs on timescales ranging from milliseconds to hours to days.
      This paper relates the theoretical and methodological developments in the study
      of interval timing in the seconds, minutes and hours range to research on the
      anticipatory activity induced by regularly timed daily meals. Daily food
      anticipatory activity (FAA) is entrained by procedures which are formally
      identical to procedures studied in Pavlovian and operant conditioning except for
      the long duration of the interval between feeding opportunities. As in FAA, the
      conditioning procedures induce orderly anticipatory activity in advance of food
      presentation. During the interval between foods the behaviors that express
      anticipation change as the interval progresses. Consequently, no single response
      represents a pure measure of anticipation. The ability to distinguish between
      properties of general anticipatory timing mechanisms such as the scalar property
      (Gibbon, 1977) and dynamic properties of specific response output systems has
      been facilitated by teaching animals to use arbitrary anticipatory responses like
      bar-pressing to obtain food. Interval timing research highlights the importance
      of identifying the mechanisms of perception, memory, decision making and
      motivation that all contribute to food anticipation. We suggest that future work
      focused on the similarities and differences in the neural bases of FAA and
      interval timing may be useful in unravelling the mechanisms mediating timing
      behavior.

PMID- 19863658
TI  - Neurogenetics of food anticipation.
AB  - Circadian clocks enable the organisms to anticipate predictable cycling events in
      the environment. The mechanisms of the main circadian clock, localized in the
      suprachiasmatic nuclei of the hypothalamus, involve intracellular autoregulatory
      transcriptional loops of specific genes, called clock genes. In the
      suprachiasmatic clock, circadian oscillations of clock genes are primarily reset
      by light, thus allowing the organisms to be in phase with the light-dark cycle.
      Another circadian timing system is dedicated to preparing the organisms for the
      ongoing meal or food availability: the so-called food-entrainable system,
      characterized by food-anticipatory processes depending on a circadian clock whose
      location in the brain is not yet identified with certainty. Here we review the
      current knowledge on food anticipation in mice lacking clock genes or feeding
      related genes. The food-entrainable clockwork in the brain is currently thought
      to be made of transcriptional loops partly divergent from those described in the
      light-entrainable suprachiasmatic nuclei. Possible confounding effects associated
      with behavioral screening of meal anticipation in mutant mice are also discussed.

PMID- 19863659
TI  - Lesion studies targeting food-anticipatory activity.
AB  - Behavior ablation remains a powerful, if not cutting-edge, approach for
      localization of function within the nervous system. The initial discovery of the
      suprachiasmatic nuclei as the site of the mammalian light-entrainable circadian
      pacemaker is owed to this approach. Food-anticipatory activity (FAA), an output
      of a putative feeding-entrainable circadian pacemaker, is a behavior that has
      been surprisingly resilient to elimination by surgical lesion. Here we review
      this literature, with particular attention paid to recent studies aimed at
      defining the role of the dorsomedial hypothalamus in the generation of FAA. This
      literature is fraught with examples of inconsistent results among lesion studies,
      which in some cases can be accounted for by varied endpoint measures. The site of
      the feeding-entrainable circadian pacemaker, if it resides in a discrete
      structure at all, remains unknown.

PMID- 19863660
TI  - Food-entrainable circadian oscillators in the brain.
AB  - Circadian rhythms in mammalian behaviour and physiology rely on daily
      oscillations in the expression of canonical clock genes. Circadian rhythms in
      clock gene expression are observed in the master circadian clock, the
      suprachiasmatic nucleus but are also observed in many other brain regions that
      have diverse roles, including influences on motivational and emotional state,
      learning, hormone release and feeding. Increasingly, important links between
      circadian rhythms and metabolism are being uncovered. In particular, restricted
      feeding (RF) schedules which limit food availability to a single meal each day
      lead to the induction and entrainment of circadian rhythms in food-anticipatory
      activities in rodents. Food-anticipatory activities include increases in core
      body temperature, activity and hormone release in the hours leading up to the
      predictable mealtime. Crucially, RF schedules and the accompanying food
      anticipatory activities are also associated with shifts in the daily oscillation
      of clock gene expression in diverse brain areas involved in feeding, energy
      balance, learning and memory, and motivation. Moreover, lesions of specific brain
      nuclei can affect the way rats will respond to RF, but have generally failed to
      eliminate all food-anticipatory activities. As a consequence, it is likely that a
      distributed neural system underlies the generation and regulation of food
      anticipatory activities under RF. Thus, in the future, we would suggest that a
      more comprehensive approach should be taken, one that investigates the
      interactions between multiple circadian oscillators in the brain and body, and
      starts to report on potential neural systems rather than individual and discrete
      brain areas.

PMID- 19863657
TI  - The rabbit pup, a natural model of nursing-anticipatory activity.
AB  - Mother rabbits nurse their young once a day with circadian periodicity. Nursing
      bouts are brief (ca. 3 min) and occur inside the maternal burrow. Despite this
      limited contact mother rabbits and their pups are tuned to each other to ensure
      that the capacities of each party are used efficiently to ensure the weaning of a
      healthy litter. In this review we present behavioral, metabolic and hormonal
      correlates of this phenomenon in mother rabbits and their pups. Research is
      revealing that the circadian rhythm of locomotion shifts in parallel to the
      timing of nursing in both parties. In pups corticosterone has a circadian rhythm
      with highest levels at the time of nursing. Other metabolic and hormonal
      parameters follow an exogenous or endogenous rhythm which is affected by the time
      of nursing. In the brain, clock genes and their proteins (e.g. Per1) are
      differentially expressed in specific brain regions (e.g. suprachiasmatic nucleus,
      paraventricular nucleus) in relation to providing or ingesting milk in mothers
      and young, respectively. These findings suggest that circadian activities are
      modulated, in the mothers, by suckling stimulation and, in the young, by the
      ingestion of milk and/or the perception of the mammary pheromone. In conclusion,
      the rabbit pup is an extraordinary model for studying the entraining by a single
      daily food pulse with minimal manipulations. The mother offers the possibility of
      studying nursing as a non-photic synchronizer, also with minimal manipulation, as
      suckling stimulation from the litter occurs only once daily.

PMID- 19863661
TI  - FabH selectivity for anteiso branched-chain fatty acid precursors in low
      temperature adaptation in Listeria monocytogenes.
AB  - Gram-positive bacteria, including Listeria monocytogenes, adjust membrane
      fluidity by shortening the fatty acid chain length and increasing the
      proportional production of anteiso fatty acids at lower growth temperatures. The
      first condensation reaction in fatty acid biosynthesis is carried out by beta
      ketoacyl-acyl carrier protein synthase III (FabH), which determines the type of
      fatty acid produced in bacteria. Here, we measured the initial rates of FabH
      catalyzed condensation of malonyl-acyl carrier protein and alternate branched
      chain precursor acyl-CoAs utilizing affinity-purified His-tagged L. monocytogenes
      FabH heterologously expressed in Escherichia coli. Listeria monocytogenes FabH
      showed a preference for 2-methylbutyryl-CoA, the precursor of odd-numbered
      anteiso fatty acids, at 30 degrees C, which was further increased at a low
      temperature (10 degrees C), suggesting that temperature-dependent substrate
      selectivity of FabH underlies the increased formation of anteiso branched-chain
      fatty acids during low-temperature adaptation. The increased FabH preferential
      condensation of 2-methylbutyryl-CoA could not be attributed to a significantly
      higher availability of this fatty acid precursor as acyl-CoA pool levels were
      reduced similarly for all fatty acid precursors at low temperatures.

PMID- 19863662
TI  - Taxonomy, diversity and origins of symbiotic endophytes of Achnatherum sibiricum
      in the Inner Mongolia Steppe of China.
AB  - We sampled five Achnatherum sibiricum populations and documented the distribution
      and abundance of endophytes. In total, 438 fungal isolates were obtained. They
      were classified into 11 morphotypes based on growth rate and morphological
      characters including colonial morphology, the production of conidiogenous cells,
      conidial size and dimension on potato dextrose agar medium. Both tub2 and actG
      sequences identified only a single product in all representative isolates from
      three dominant morphotypes. All sequences fell in the same main clade, including
      Neotyphodium gansuense and Neotyphodium gansuense var. inebrians from another
      Achnatherum species in North China, Achnatherum inebrians, and Neotyphodium
      guerinii from European grasses Melica ciliate and Melica transsilvanica. Based on
      both morphological and phylogenetic analyses, isolates in morphotype I were
      described as representing a novel Neotyphodium species, Neotyphodium sibiricum
      sp. nov. Isolates in both morphotype II and III were identified as representing
      N. gansuense. Both tub2 and actG sequences suggested that N. sibiricum and N.
      guerinii were probably derived from a common Epichloe ancestor.

PMID- 19863663
TI  - Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis
      in macrophages.
AB  - Siderocalin is a secreted protein that binds to siderophores to prevent bacterial
      iron acquisition. While it has been shown to inhibit the growth of Mycobacterium
      tuberculosis (M.tb) in extracellular cultures, its effect on this pathogen within
      macrophages is not clear. Here, we show that siderocalin expression is
      upregulated following M.tb infection of mouse macrophage cell lines and primary
      murine alveolar macrophages. Furthermore, siderocalin added exogenously as a
      recombinant protein or overexpressed in the RAW264.7 macrophage cell line
      inhibited the intracellular growth of the pathogen. A variant form of
      siderocalin, which is expressed only in the macrophage cytosol, inhibited
      intracellular M.tb growth as effectively as the normal, secreted form, an
      observation that provides mechanistic insight into how siderocalin might
      influence iron acquisition by the bacteria in the phagosome. Our findings are
      consistent with an important role for siderocalin in protection against M.tb
      infection and suggest that exogenously administered siderocalin may have
      therapeutic applications in tuberculosis.

PMID- 19863664
TI  - Structure-based virtual screening for novel inhibitors of Japanese encephalitis
      virus NS3 helicase/nucleoside triphosphatase.
AB  - Japanese encephalitis (JE) is a significant cause of human morbidity and
      mortality throughout Asia and Africa. Vaccines have reduced the incidence of JE
      in some countries, but no specific antiviral therapy is currently available. The
      NS3 protein of Japanese encephalitis virus (JEV) is a multifunctional protein
      combining protease, helicase and nucleoside 5'-triphosphatase (NTPase)
      activities. The crystal structure of the catalytic domain of this protein has
      recently been solved using a roentgenographic method. This enabled structure
      based virtual screening for novel inhibitors of JEV NS3 helicase/NTPase. The aim
      of the present research was to identify novel potent medicinal substances for the
      treatment of JE. In the first step of studies, the natural ligand ATP and two
      known JEV NS3 helicase/NTPase inhibitors were docked to their molecular target.
      The refined structure of the enzyme was used to construct a pharmacophore model
      for JEV NS3 helicase/NTPase inhibitors. The freely available ZINC database of
      lead-like compounds was then screened for novel inhibitors. About 1,161,000
      compounds have been screened and 15 derivatives of the highest scores have been
      selected. These compounds were docked to the JEV NS3 helicase/NTPase to examine
      their binding mode and verify screening results by consensus scoring procedure.

PMID- 19863665
TI  - Molecular characterization of poliovirus isolates from children who contracted
      vaccine-associated paralytic poliomyelitis (VAPP) following administration of
      monovalent type 3 oral poliovirus vaccine in the 1960s in Hungary.
AB  - Hungarian children were immunized with monovalent oral poliovaccine (mOPV)
      delivered at 6-week intervals in the order Sabin 1, Sabin 3, Sabin 2, from 1959
      until 1992. During that period, 90 cases of vaccine-associated paralytic
      poliomyelitis (VAPP) were reported, 52 of which were associated with Sabin 3
      related virus (76% of VAPP cases with virologic data). Because of renewed
      interest in type 3 mOPV (mOPV3), molecular methods were used to reanalyze 18 of
      the Sabin 3-related isolates from 15 VAPP patients, confirming the original
      identification. All isolates had the U472C 5'-untranslated region (5'-UTR)
      substitution associated with reversion to neurovirulence, and from zero to seven
      nucleotide substitutions in the virus protein 1 (VP1) region. No evidence was
      found for prolonged mOPV3 replication in the VAPP patients or for spread of Sabin
      3-related viruses beyond close vaccinee contacts. The VAPP diseases were
      prevented by a single dose of inactivated poliovirus vaccine from 1992 to 2006 in
      Hungary, as proved by continuous surveillance of acute flaccid paralysis.

PMID- 19863666
TI  - Osteoporosis, the risk of vertebral fracture, and periodontal disease in an
      elderly group in Mexico City.
AB  - OBJECTIVES: The aims of this study were to identify the possible association of
      osteoporosis, fracture risk and periodontitis, and consider the role of
      pharmacological treatment of osteoporosis and the periodontal condition. METHODS:
      Patients aged 60 and older from the Mexican National Medical Science and
      Nutrition Institute Salvador Zubiran participated in the study. DXA was used to
      assess osteoporosis and risk of vertebral fracture. A modified version of the
      extent and severity index (ESI) was applied to evaluate periodontitis (cut-off
      point for attachment loss >= 4 mm) and all teeth were examined. RESULTS: One
      hundred and sixty-six patients were examined, 88.6% were females, 47.0% had
      osteoporosis and 38.6% showed a high risk of fracture. The modified ESI was 5.13
      mm (SD 1.4), 57.8% (SD 29.7). The model for periodontitis severity showed an
      association with oral hygiene (OR = 1.85) and use of osteoporosis medication (OR
      = 0.43). The model for the extent of periodontitis identified an association with
      smoking (OR = 2.37), osteoporosis (OR = 1.82) and osteoporosis medication (OR =
      0.36). The model for tooth loss detected an association with fracture risk (OR =
      3.02) and osteoporosis medication (OR = 0.33). CONCLUSION: Periodontitis extent
      was associated with osteoporosis, and tooth loss with fracture risk.

PMID- 19863667
TI  - BmHrp28 is a RNA-binding protein that binds to the female-specific exon 4 of
      Bombyx mori dsx pre-mRNA.
AB  - The Bombyx mori sex determination gene Bmdsx is alternatively spliced in the male
      and female to produce the male- and female-specific proteins. In an effort to
      better understand the mechanism of the alternative splicing regulation of Bmdsx,
      we conducted a gel-shift assay followed by LC-MS/MS analysis to identify the
      putative proteins bound to the cis-element CE1+6 in the exon 4 of Bmdsx. A
      protein named as BmHrp28 which is homologous to the Drosophila Hrp48, a member of
      the hnRNPA/B family, was identified and expressed in Escherichia coli for testing
      RNA-protein binding in vitro. All of the results showed that BmHrp28 specifically
      bound to the CE1+6 RNA probe. BmHrp28 has two RNA recognition motifs at the N
      terminal and a glycine-rich motif at the C-terminal. It might be one of the
      factors involved in the male-specific splicing of Bmdsx.

PMID- 19863670
TI  - A common haplotype of protamine 1 and 2 genes is associated with higher sperm
      counts.
AB  - Sperm chromatin compaction in the sperm head is achieved when histones are
      replaced by protamines during spermatogenesis. Haploinsufficiency of the
      protamine 1 (PRM1) or PRM2 gene causes infertility in mice. However, the
      published data remain inconclusive about a role of PRM1/2 variants in male
      infertility and their association with semen parameters. By full sequence
      analysis, we assessed the frequency of sequence variations in PRM1 and PRM2 in
      three groups of Caucasian patients with idiopathic teratozoospermia and normal (n
      = 88) or reduced sperm concentration (n = 83) and in men with a high percentage
      of normal sperm morphology and normal concentrations (n = 77). Two rare (c.54G>A
      and c.102G>T) and one common SNP (c.230A>C) were identified in PRM1. In PRM2,
      some rare heterozygous mutations and the two common intronic SNPs 298G>C and
      373C>A were detected. None of the PRM1/2 variants was associated with
      teratozoospermia or individually with other semen parameters. However,
      significant linkage disequilibrium was detected between the common SNPs of PRM1
      and PRM2 which formed haplotypes. Analysis of the pooled group (n = 248) revealed
      that homozygous carriers of the common haplotype ACC had a twofold higher sperm
      concentration and count than men lacking this haplotype, with sperm counts of
      heterozygotes for ACC being midway between the homozygotes. This markedly
      decreased sperm output might either be caused by spermatozoa lacking the ACC
      haplotype not being viable, or subject to negative selection. In addition, a
      significant deviation from Hardy-Weinberg-Equilibrium of these SNPs might
      indicate natural selection in favour of the ACC allele which leads to higher
      sperm output and therefore better fertility. In conclusion, for the first time we
      describe an association of a common haplotype formed by PRM1 and PRM2 with sperm
      output in a large group of men.

PMID- 19863669
TI  - RNA interference directed against ribosomal protein S3a suggests a link between
      this gene and arrested ovarian development during adult diapause in Culex
      pipiens.
AB  - Arrested ovarian development is a key characteristic of adult diapause in the
      mosquito Culex pipiens. In this study we propose that ribosomal protein S3a
      (rpS3a), a small ribosomal subunit, contributes to this shutdown. RpS3a is
      consistently expressed in females of C. pipiens that do not enter diapause, but
      in females programmed for diapause, expression of the rpS3a transcript is
      dramatically reduced for a brief period in early diapause (7-10 days after adult
      eclosion). RNA interference directed against rpS3a in nondiapausing females
      arrested follicle development, mimicking the diapause state. The effect of the
      dsRNA injection faded within 10 days, allowing the follicles to grow again, thus
      the suppression of rpS3a caused by RNAi did not permanently block ovarian
      development, implying that a brief suppression of rpS3a is not the only factor
      contributing to the diapause response. The arrest in development that we observed
      in dsRNA-injected females could be reversed with a topical application of
      juvenile hormone III, an endocrine trigger known to terminate diapause in this
      species. Though we speculate that many genes contribute to the diapause syndrome
      in C. pipiens, our results suggest that a shut down in the expression of rpS3a is
      one of the important components of this developmental response.

PMID- 19863671
TI  - Special issue: 26th Annual Symposium of Nonhuman Primate Models for AIDS.
      Introduction.

PMID- 19863672
TI  - Viral interleukin-6 encoded by rhesus macaque rhadinovirus is associated with
      lymphoproliferative disorder (LPD).
AB  - BACKGROUND: Rhesus macaques (RM) co-infected with simian immunodeficiency virus
      (SIV) and rhesus macaque rhadinovirus (RRV) develop abnormal cellular
      proliferations characterized as extra-nodal lymphoma and retroperitoneal
      fibromatosis (RF). RRV encodes a viral interleukin-6 (vIL-6), much like Kaposi's
      sarcoma-associated herpesvirus, and involvement of the viral cytokine was
      examined in proliferative lesions. METHODS: Formalin fixed tissue from RM co
      infected with SIV and RRV were analyzed for RRV genomes by in situ hybridization
      and RRV vIL-6 expression by immunofluorescence analysis. RESULTS: In situ
      hybridization analysis indicated that RRV is present in both types of lesions.
      Immunofluorescence analysis of different lymphomas and RF revealed positive
      staining for vIL-6. Similarly to KS, RF lesion is positive for vimentin, CD117 (c
      kit), and smooth muscle actin (SMA) and contains T cell, B cell and
      monocytes/macrophage infiltrates. CONCLUSIONS: Our data support the idea that vIL
      6 may be critical to the development and progression of lymphoproliferative
      disorder in RRV/SIV-infected RM.

PMID- 19863668
TI  - Genes related to immunity, as expressed in the alfalfa leafcutting bee, Megachile
      rotundata, during pathogen challenge.
AB  - Virtually nothing is known about disease resistance in solitary bees, so
      expressed sequence tag (EST) databases were developed to search for immune
      response genes in the alfalfa leafcutting bee. We identified 104 putative
      immunity-related genes from both healthy and pathogen-challenged bee larvae, and
      12 more genes using PCR amplification. The genes identified coded for proteins
      with a wide variety of innate immune response functions, including pathogen
      recognition, phagocytosis, the prophenoloxidase cascade, melanization,
      coagulation and several signalling pathways. Some immune response genes were
      highly conserved with honey bee genes, and more distantly related to other
      insects. The data presented provides the first analysis of immune function in a
      solitary bee and provides a foundation for the further analysis of gene
      expression patterns in bees.

PMID- 19863673
TI  - Vaccination with SIVmac239Deltanef activates CD4+ T cells in the absence of CD4 T
      cell loss.
AB  - BACKGROUND: Pathogenic HIV and SIV infections characteristically deplete central
      memory CD4(+) T cells and induce chronic immune activation, but it is
      controversial whether this also occurs after vaccination with attenuated SIVs and
      whether depletion or activation of CD4(+) T-cell play roles in protection against
      wild-type virus challenge. METHODS: Rhesus macaques were vaccinated with
      SIVmac239Deltanef and quantitative and phenotypic polychromatic flow cytometry
      analyses were performed on mononuclear cells from blood, lymph nodes and rectal
      biopsies. RESULTS: Animals vaccinated with SIVmac239Deltanef demonstrated no loss
      of CD4(+) T cells in any tissue, and in fact CCR5(+) and CD28(+)CD95(+) central
      memory CD4(+) T cells were significantly increased. In contrast, CD4(+) T-cell
      numbers and CCR5 expression significantly declined in unvaccinated controls
      challenged with SIVmac239. Also, intracellular Ki67 increased acutely as much as
      3-fold over baseline in all tissues after SIVmac239Deltanef vaccination then
      declined following primary infection. CONCLUSION: We demonstrated in this study
      that SIVmac239Deltanef vaccination did not deplete CD4(+) T cells but transiently
      activated and expanded the memory cell population. However, increases in numbers
      and activation of memory CD4(+) T cells did not appear to influence protective
      immunity.

PMID- 19863674
TI  - Resources for genetic management and genomics research on non-human primates at
      the National Primate Research Centers (NPRCs).
AB  - The National Primate Research Centers (NPRCs) established Working Groups (WGs)
      for developing resources and mechanisms to facilitate collaborations among non
      human primate (NHP) researchers. Here we report the progress of the Genome
      Banking and the Genetics and Genomics WGs in developing resources to advance the
      exchange, analysis and comparison of NHP genetic and genomic data across the
      NPRCs. The Genome Banking WG has established a National NHP DNA bank comprising
      1250 DNA samples from unrelated animals and family trios from the 10 NHP species
      housed within the NPRC system. The Genetics and Genomics WG is developing SNP
      arrays that will provide a uniform, highly informative, efficient and low-cost
      method for rhesus and long-tailed macaque genotyping across the eight NPRCs. This
      WG is also establishing a Biomedical Informatics Research Network-based portal
      for shared bioinformatics resources including vital statistics, genotype and
      population data and information on the National NHP DNA bank.

PMID- 19863675
TI  - CD4 T cell subsets in the mucosa are CD28+Ki-67-HLA-DR-CD69+ but show
      differential infection based on alpha4beta7 receptor expression during acute SIV
      infection.
AB  - BACKGROUND: CD4 T cell depletion in the mucosa has been well documented during
      acute HIV and SIV infections. The demonstration the HIV/SIVcan use the
      alpha4beta7 receptor for viral entry suggests that these viruses selectively
      target CD4 T cells in the mucosa that express high levels of alpha4beta7
      receptor. METHODS: Mucosal samples obtained from SIV infected rhesus macaques
      during the early phase of infection were used for immunophenotypic analysis. CD4
      T cell subsets were sorted based on the expression of beta7 and CD95 to quantify
      the level of SIV infection in different subsets of CD4 T cells. Changes in IL-17,
      IL-21, IL-23 and TGFbeta mRNA expression was determined using Taqman PCR.
      RESULTS: CD4 T cells in the mucosa were found to harbor two major population of
      cells; -25% of CD4 T cells expressed the alpha4(+)beta7(hi) phenotype, whereas
      the rest of the 75% expressed an alpha4(+)beta7(int) phenotype. Both the subsets
      were predominantly CD28(+)Ki-67(-)HLA-DR(-) but CD69(+), and expressed detectable
      levels of CCR5 on their surface. Interestingly, however, alpha4(+)beta7(hi)CD4 T
      cells were found to harbor more SIV than the alpha4(+)beta7(int) subsets at day
      10 pi. Early infection was associated with a dramatic increase in the expression
      of IL-17, and IL-17 promoting cytokines IL-21, IL-23, and TGFbeta that stayed
      high even after the loss of mucosal CD4 T cells. CONCLUSIONS: Our results suggest
      that the differential expression of the alpha4beta7 receptor contributes to the
      differences in the extent of infection in CD4 T cell subsets in the mucosa. Early
      infection is associated dysregulation of the IL-17 network in mucosal tissues
      involves other non-Th-17 cells that likely contributes to the pro-inflammatory
      environment in the mucosa during acute stages of SIV infection.

PMID- 19863676
TI  - Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance
      observed in peripheral blood during simian immunodeficiency virus infection.
AB  - BACKGROUND: Human immuno deficiency virus and simian immunodeficiency virus
      infections are characterized by a severe loss of Th-17 cells (IL-17(+)CD4(+) T
      cells) that has been associated with disease progression and systemic
      dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to
      repopulation of CD4(+) T cells in peripheral tissues with little sustainable
      repopulation in mucosal tissues. Given the central importance of Th-17 cells in
      mucosal homeostasis, it is not known if the failure of ART to permanently
      repopulate mucosal tissues is associated with a failure to restore Th-17 cells
      that are lost during infection. METHODS: Dynamics of alpha4(+)beta7(hi) CD4(+) T
      cells in peripheral blood of SIV infected rhesus macaques were evaluated and
      compared to animals that were treated with ART. The frequency of Th-17 and Tc-17
      cells was determined following infection and after therapy. Relative expression
      of IL-21, IL-23, and TGFbeta was determined using Taqman PCR. RESULTS: Treatment
      of SIV infected rhesus macaques with anti-retroviral therapy was associated with
      a substantial repopulation of mucosal homing alpha4(+)beta7(hi)CD4(+) T cells in
      peripheral blood. This repopulation, however, was not accompanied by a
      restoration of Th-17 responses. Interestingly, SIV infection was associated with
      an increase in Tc-17 responses (IL-17(+)CD8(+) T cells) suggesting to a skewing
      in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a
      predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during
      the course of therapy suggesting that ART failed to correct the imbalance in Th
      17 : Tc-17 responses induced following SIV infection. CONCLUSIONS: ART was
      associated with substantial repopulation of alpha4(+)beta7(hi) CD4(+) T cells in
      peripheral blood with little or no rebound of Th-17 cells. On the other hand,
      repopulation of alpha4(+)beta7(hi) CD4(+) T cells was accompanied by persistence
      of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17 and
      Tc-17 responses likely plays a role in disease progression.

PMID- 19863677
TI  - Macaca fascicularis are highly susceptible to an RT-SHIV following intravaginal
      inoculation: a new model for microbicide evaluation.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
      (RT) is a major target for antiretroviral strategy to block or curtail HIV
      infection. A suitable RT-SHIV/macaque model is urgently needed for the evaluation
      of HIV/AIDS therapies and microbicides specifically targeting HIV-1 RT. METHODS:
      Fifteen cynomolgus macaques (Macaca fascicularis) were divided into three groups
      (n = 5) and intravaginally inoculated with 4800, 1200, or 300 TCID(50) of RT
      SHIVtc. Systemic infections of RT-SHIVtc exposed macaques were determined by both
      virological and immunologic parameters during 24 weeks post-challenge. RESULTS:
      Within 2 weeks post-inoculation, 13 of 15 macaques became infected as confirmed
      by virus isolation, plasma viral RNA, proviral DNA, declined CD4(+)T cell counts
      in peripheral blood and seroconversion. CONCLUSIONS: Results serve to validate
      the infectivity and pathogenicity of RT-SHIVtc following vaginal exposure in M.
      fascicularis. This RT-SHIVtc/macaque model could be suitable for the pre-clinical
      evaluation of non-nucleoside RT inhibitor-based anti-HIV microbicides.

PMID- 19863680
TI  - The prevalence of vitamin D abnormalities in South Asians with type 2 diabetes
      mellitus in the UK.
AB  - BACKGROUND: The high prevalence of both hypovitaminosis D and type 2 diabetes
      (T2DM) in the Asian community is well recognised, but the impact of diabetes on
      vitamin D status and vice versa, has not been well reported. AIMS: To determine
      the prevalence of hypovitaminosis D in Asian patients with T2DM and its impact on
      glycaemic control. METHODS: A cross-sectional study was conducted in a tertiary
      referral centre in the UK. Two hundred and ten Asian patients aged more than 40
      years were included (170 with and 40 without T2DM). Each had a standard bone
      profile (serum calcium, phosphate and alkaline phosphatase), serum parathyroid
      hormone and 25-hydroxycholecalciferol. RESULTS: The prevalence of low serum 25
      hydroxyvitamin D (< 50 nmol/l) was high in the group as a whole (> 80%) and more
      common in diabetics compared with controls (83% vs. 70%; p = 0.07). This was
      particularly so in men (82.5% vs. 57.9%; p = 0.02). HbA1c was higher in women
      with vitamin D deficiency (< 12.5 nmol/l) (8.11 +/- 1.11% vs. 7.33 +/- 1.32%, p =
      0.046). In logistic regression analysis, T2DM was an independent predictor of
      hypovitaminosis D. In linear regression analysis, vitamin D deficiency was
      independently related to HbA1c in women with T2DM. CONCLUSIONS: Hypovitaminosis D
      remains a major public health issue in the Asian population and is exaggerated in
      patients with T2DM. The fact that vitamin D deficient women had higher HbA1c
      levels raises the possibility that vitamin D replacement may improve glycaemic
      control.

PMID- 19863681
TI  - Molecular analysis of HumDN1 VNTR polymorphism of the human deoxyribonuclease I
      in systemic lupus erythematosus.
AB  - Deoxyribonuclease I (DNASE1) may be responsible for the removal of DNA from
      nuclear antigens at sites of high cell turnover, thus preventing the onset of
      systemic lupus erythematosus (SLE). The purpose of this study was to screen
      DNASE1 gene for mutations that may have an effect on susceptibility to develop
      SLE. DNA was extracted from 76 Kuwaiti SLE patients and 92 race-matched controls.
      PCR-direct sequencing was used to screen DNASE1 promoter, coding sequence and
      exon-intron boundaries for mutation. Association of genomic variations was
      assessed using a Chi-square test. Molecular analysis of the DNASE1 gene did not
      reveal any mutation. However, a 56-bp repeat was detected in intron4 which was
      previously reported and named HumDN1. The allelic and genotypic distributions of
      the HumDN1 VNTR were compared between SLE patients and healthy subjects. Alleles
      were denoted as 2, 3, 4, 5 and 6 corresponding to the number of repeats of the 56
      bp unit. Alleles 4, 5, and 6 showed significant association with SLE. Allele 5
      showed the highest association [chi(2) = 32.57; P < or = 0.001; OR = 4.16; 95%
      CI: (2.55-6.79)]. Association of allele 5 was also found at the genotypic level,
      where genotype 5/5 is more prevalent in SLE subjects as compared with controls
      (17% versus 9%). We report a significant association of HumDN1 VNTR polymorphism
      in DNASE1 gene with SLE. Further functional assays needed to assess the effect of
      this VNTR on DNASE1 activity and its association with SLE.

PMID- 19863683
TI  - International Council for Standardization in Haematology technical report 1-2009:
      new reference material for haemiglobincyanide for use in standardization of blood
      haemoglobin measurements.
AB  - The International Council for Standardization in Haematology (ICSH) in
      conjunction with Eurotrol, B.V. has released a new lot of the haemiglobincyanide
      or haemoglobin standard. This technical report describes the purpose, methodology
      in manufacturing, summary of value assignment data and availability of this
      standard material used for the standardization and calibration of whole blood
      haemoglobin measurements on most haemoglobinometers and automated blood cell
      counters throughout the world.

PMID- 19863682
TI  - Expression patterns of specific promyelocytic/retinoic acid receptor-alpha
      transcripts in patients with acute promyelocytic leukemia.
AB  - Several additional promyelocytic/retinoic acid receptor-alpha (PML/RARalpha)
      transcripts besides bcr1, bcr2, and bcr3 have been identified in patients with
      acute promyelocytic leukemia (APL). However, the expression levels of these
      specific isoforms and their clinical relevance have not been studied to date. The
      real-time quantitative polymerase chain reaction was established to detect each
      specific isoform of PML/RARalpha transcripts (bcr1/2, P46R3, P4R3, bcr3, and
      P2R3) in 46 APL patients. Whereas P46R3 and P4R3 isoforms were concurrently
      expressed in both bcr1- and bcr2-positive patients, P2R3 isoform was expressed
      only in bcr3-positive patients. A total of 13 patients had lower expression of
      bcr1/2 (median 11.60%, 0.86-108.51%) than that of P46R3 (median 14.26%, 6.03
      222.91%; P = 0.001). The expression level of P4R3 (median 19.10%, 0.71-266.19%)
      was lower than the sum of bcr1/2 and P46R3 (median 37.94%, 9.62-403.51%) in all
      cases (P < 0.001). All 16 cases with bcr3 had concurrent low expression of P2R3
      (P < 0.001). Structural analysis revealed that both P4R3 and P2R3 splicing
      resulting in the generation of a premature termination codon, which was
      recognized by nonsense-mediated decay (NMD). We suggest that alternative splicing
      of PML/RARalpha transcripts might be involved in NMD and each isoform should be
      quantified to further understand the pathogenesis of APL, stratify the risk of
      relapse, and monitor minimal residual disease.

PMID- 19863684
TI  - Features of Saccharomyces cerevisiae as a culture starter for the production of
      the distilled sugar cane beverage, cachaca in Brazil.
AB  - AIMS: To evaluate the dominance and persistence of strains of Saccharomyces
      cerevisiae during the process of sugar cane fermentation for the production of
      cachaca and to analyse the microbial compounds produced in each fermentative
      process. METHODS AND RESULTS: Three S. cerevisiae strains were evaluated during
      seven consecutive 24-h fermentation batches using recycled inocula. The UFLA CA
      116 strain had the largest population of viable organisms, and the maximum
      population was achieved in the fourth batch after 96 h of fermentation. The UFLA
      CA 1162 and UFLA CA 1183 strains grew more slowly, and the maximum population was
      reached in the seventh batch. Molecular characterization of isolated yeast cells
      using PFGE (pulse field gel electrophoresis) revealed that more than 86% of the
      isolates corresponded to the initially inoculated yeast strain. The concentration
      of aldehydes, esters, methanol, alcohol and volatile acids in the final-aged
      beverages were within the legal limits. CONCLUSIONS: Cachaca produced by select
      yeast strains exhibits analytical differences. UFLA CA 1162 and UFLA CA 116 S.
      cerevisiae isolates can be considered the ideal strains for the artisanal
      production of cachaca in Brazil. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of
      select yeast strains can improve the quality and productivity of cachaca
      production. Our findings are important for the appropriate monitoring of yeast
      during sugar cane fermentation. In addition, we demonstrate that UFLA CA 116 and
      UFLA CA 1162, the ideal yeast strains for cachaca production, are maintained at a
      high population density. The persistence of these yeast strains in the
      fermentation of sugar cane juice promotes environmental conditions that prevent
      or decrease bacterial contamination. Thus, the use of select yeast strains for
      the production of cachaca is a viable economic alternative to standardize the
      production of this beverage.

PMID- 19863685
TI  - Fungal microbiota dynamics as a postmortem investigation tool: focus on
      Aspergillus, Penicillium and Candida species.
AB  - AIMS: To investigate the presence of fungi during three human decomposition
      stages: bloated, putrefaction and skeletonization. METHODS AND RESULTS: The
      samples were gathered in the city of Fortaleza, Ceara, Brazil, from the public
      morgue and cemeteries. The material was submitted to conventional mycological
      procedures by direct examination and macro/micro morphological and biochemical
      analyses. The main fungi isolated were Aspergillus spp., Penicillium spp. and
      Candida spp. in the bloated stage (n = 34 cadavers) and in the putrefaction stage
      (n = 6 cadavers), while in the skeletonization stage (n = 20 cadavers), the main
      fungi were Aspergillus spp., Penicillium spp. and Mucor sp. CONCLUSIONS:
      Aspergillus, Penicillium and Candida species were associated with decomposed
      human cadavers. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings enable
      tracing out the profile of fungal communities of human cadavers for the first
      time. However, much more research will be necessary to develop this new segment
      of mycology and to enable its routine use in forensic science.

PMID- 19863686
TI  - Comparative studies of microbial populations in the rumen, duodenum, ileum and
      faeces of lactating dairy cows.
AB  - AIMS: Understanding factors that influence the composition of microbial
      populations of the digestive system of dairy cattle will be key in regulating
      these populations to improve animal performance. Although rumen microbes are well
      studied, little is known of the dynamics and role of microbial populations in the
      small intestine of cows. Comparisons of fingerprints of microbial populations
      were used to investigate the effects of gastrointestinal (GI) segment and animal
      on community structure. METHODS AND RESULTS: Samples from four lactating dairy
      cows with ruminal, duodenal and ileal cannulae were collected. Terminal
      restriction fragment length polymorphism (T-RFLP) comparisons of small subunit
      rRNA genes revealed differences in microbial populations between GI segments (P <
      0.05). No significant differences in either methanogen populations or microbial
      community profiles between animals were observed. Quantitative PCR was used to
      assay relative changes in methanogen numbers compared to procaryote rRNA gene
      numbers, and direct microscopic counts were used to enumerate total procaryote
      numbers of the duodenal and ileal samples. CONCLUSIONS: T-RFLP comparisons
      illustrate significant changes in microbial diversity as digesta passes from one
      segment to another. Direct counts indicate that microbial numbers are reduced by
      eight orders of magnitude from the rumen, through the abomasum, and into the
      duodenum (from c. 10(12) to c. 3.6 x 10(4) cells per ml). Quantitative PCR
      analyses of rRNA genes indicate that methanogens are present in the duodenum and
      ileum. SIGNIFICANCE AND IMPACT OF THE STUDY: The contribution of microbial
      populations of the small intestine to the nutrition and health of cattle is
      seldom addressed but warrants further investigation.

PMID- 19863687
TI  - Vibrio nigripulchritudo monitoring and strain dynamics in shrimp pond sediments.
AB  - AIMS: A description of bacterial pathogens in shrimp ponds is necessary to
      understand their pathogenesis. Vibrio nigripulchritudo was shown to contain
      saprophytic and pathogenic strains among New Caledonian isolates. We established
      a method to map the development of V. nigripulchritudo in pond sediments at three
      different genetic levels: the species level, then at the pathogenic cluster level
      and finally at the plasmid level, present only in all highly pathogenic isolates.
      METHODS AND RESULTS: PCR methods were applied to shrimp pond sediments both
      before and after a mortality outbreak. Using crude samples, the species V.
      nigripulchritudo is not detected at first (0/42 samples at day 56 post stocking)
      but appears frequently in the sediments after the mortality event (30/42 at day
      107). The distribution of strains from the pathogenic cluster of V.
      nigripulchritudo also follows this pattern. In contrast, the pSFn1 virulence
      associated plasmid was detected in one sample at day 56 and none at day 107. An
      enrichment method was developed to lower the detection limits of our assays.
      After enrichment, the species V. nigripulchritudo was detected in all samples at
      both dates. The number of samples positive for pSFn1 was 42/42 samples at day 56
      and 29/42 at day 107. CONCLUSIONS: These results show that the sediments contain
      V. nigripulchritudo, notably pathogenic strains. Surprisingly, the virulence
      associated plasmid pSFn1 found in all V. nigripulchritudo isolated from moribund
      shrimp appears less frequently in sediments, possibly being useless or even
      detrimental to its recipient bacteria in this environment. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study confirms the presence of pathogenic V.
      nigripulchritudo strains in shrimp pond sediment before a mortality outbreak
      complying with a previous hypothesis that sediments could be the infecting
      reservoir. After the outbreak, both total V. nigripulchritudo and pathogenic
      strains populations have largely increased, possibly contributing to the
      recurrent mortality observed in this shrimp vibriosis.

PMID- 19863688
TI  - Complete genome sequence of a newly isolated lytic bacteriophage, EFAP-1 of
      Enterococcus faecalis, and antibacterial activity of its endolysin EFAL-1.
AB  - AIMS: In this work, we aimed to identify an effective treatment of infections
      caused by Enterococcus spp. strains resistant to conventional antibiotics.
      METHODS AND RESULTS: We report the isolation and characterization of a new lytic
      bacteriophage, designated bacteriophage EFAP-1, that is capable of lysing
      Enterococcus faecalis bacteria that exhibit resistance to multiple antibiotics.
      EFAP-1 has low sequence similarity to all known bacteriophages. Transmission
      electron microscopy confirmed that EFAP-1 belongs to the Siphoviridae family. A
      putative lytic protein of EFAP-1, endolysin EFAL-1, is encoded in ORF 2 and was
      expressed in Escherichia coli. Recombinant EFAL-1 had broad-spectrum lytic
      activity against several Gram-positive pathogens, including Ent. faecalis and
      Enterococcus faecium. CONCLUSIONS: The complete genome sequence of the newly
      isolated enterococcal lytic phage was analysed, and it was demonstrated that its
      recombinant endolysin had broad lytic activity against various Gram-positive
      pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteriophage EFAP-1 and its
      lytic protein, EFAL-1, can be utilized as potent antimicrobial agents against
      Enterococcus spp. strains resistant to conventional antibiotics in hospital
      infections and also as environmental disinfectants to control disease-causing
      Enterococcus spp. in dairy farms.

PMID- 19863689
TI  - Pathogenic potential and horizontal gene transfer in ovine gastrointestinal
      Escherichia coli.
AB  - AIMS: To demonstrate that a thorough characterization and virulotyping of
      Escherichia coli strains isolated from sheep over time leads to new insights into
      ovine E. coli potentially becoming human pathogens through horizontal gene
      transfer. METHODS AND RESULTS: One hundred and fifty E. coli isolates from two
      sheep, sampled over 3 weeks, were characterized by serotyping, virulotyping,
      genotyping using multiple locus variable number tandem repeats analysis (MLVA)
      and susceptibility to phage infection in vitro. The 35 MLVA profiles and the
      serotype and virulotypes of the strains were closely associated. Many MLVA
      profiles differed in one locus independent of serotypes. Escherichia coli
      isolates of the same serotype or virulotype had identical or very similar MLVA
      profiles. No transductants that incorporated the bacteriophages were found in
      vivo, but six E. coli isolates were susceptible to the phage infection in vitro.
      Changes in MLVA profiles were seen after acquisition of Stx phages in vitro only.
      CONCLUSIONS: The sheep carried Stx phage susceptible E. coli that possessed
      virulence markers associated with human pathogenicity. Changes in bacterial
      genomes by phage transfer may complicate outbreak source investigations. Serotype
      has to be taken into account when evaluating strain relationships by MLVA.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Sheep carry E. coli that encode for
      virulence markers and belong to serogroups known to be human pathogens. In
      addition, a selection of isolates was found to be susceptible to horizontal
      transfer of Shiga toxin genes by means of bacteriophages in vitro, and the
      transfer resulted in a discernible change of the MLVA patterns of E. coli.

PMID- 19863690
TI  - Copper-resistant halophilic bacterium isolated from the polluted Maruit Lake,
      Egypt.
AB  - AIMS: To isolate and characterize copper-resistant halophilic bacteria from the
      polluted Maruit Lake, Egypt and identify the role of plasmids in toxic metal
      resistance. METHODS AND RESULTS: We isolated strain MA2, showing high copper
      resistance up to the 1.5 mmol l(-1) concentration; it was also resistant to other
      metals such as nickel, cobalt and zinc and a group of antibiotics. Partial 16S
      rRNA analysis revealed that strain MA2 belonged to the genus Halomonas. Copper
      uptake, measured by atomic absorption spectrophotometery, was higher in the
      absence of NaCl than in the presence of 0.5-1.0 mol l(-1) NaCl during 5-15 min of
      incubation. Cell fractionation and electron microscopic observation clarified
      that most of the copper accumulated in the outer membrane and periplasmic
      fractions of the cells. Plasmid screening yielded two plasmids: pMA21 (11 kb) and
      pMA22 (5 kb). Plasmid curing resulted in a strain that lost both the plasmids and
      was sensitive to cobalt and chromate but not copper, nickel and zinc. This cured
      strain also showed weak growth in the presence of 0.5-1.0 mol l(-1) NaCl. Partial
      sequencing of both plasmids led to the identification of different toxic metals
      transporters but copper transporters were not identified. CONCLUSIONS: The
      highest cell viability was found in the presence of 1.0 mol l(-1) NaCl at
      different copper concentrations, and copper uptake was optimal in the absence of
      NaCl. Plasmid pMA21 encoded chromate, cobalt, zinc and cadmium transporters,
      whereas pMA22 encoded specific zinc and RND (resistance, nodulation, cell
      division) efflux transporters as well as different kinds of metabolic enzymes.
      Copper resistance was mainly incorporated in the chromosome. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Strain MA2 is a fast and efficient tool for copper
      bioremediation and the isolated plasmids show significant characteristics of both
      toxic metal and antibiotic resistance.

PMID- 19863691
TI  - Assessing the impact of various ensilage factors on the fermentation of grass
      silage using conventional culture and bacterial community analysis techniques.
AB  - AIMS: Grass silage is an important ruminant feedstuff on farms during winter. The
      ensilage of grass involves a natural lactic acid bacterial fermentation under
      anaerobic conditions, and numerous factors can influence the outcome of
      preservation. The aim of this study was to investigate the effect of dry matter
      concentration, ensiling system, compaction and air infiltration on silage
      bacterial community composition. METHODS AND RESULTS: The impact of these factors
      was examined using conventional methods of microbial analysis and culture
      independent Terminal Restriction Fragment Length Polymorphism (T-RFLP). Silage
      fermentation was restricted in herbage with a high dry matter concentration, and
      this was reflected in a shift in the bacterial population present. In contrast,
      ensiling system had little effect on bacterial community composition. Air
      infiltration, in the absence of compaction, altered silage bacterial community
      composition and silage pH. CONCLUSIONS: Dry matter concentration and the absence
      of compaction were the main factors affecting silage microbial community
      composition, and this was reflected in both the conventional culture-based and T
      RFLP data. SIGNIFICANCE AND IMPACT OF THE STUDY: T-RFLP proved a useful tool to
      study the factors affecting ensilage. Apart from monitoring the presence or
      absence of members of the population, shifts in the relative presence of members
      could be monitored.

PMID- 19863693
TI  - Tissue inhibitor of metalloproteinases-1-induced scattered liver metastasis is
      mediated by host-derived urokinase-type plasminogen activator.
AB  - Paradoxically, not only proteinases but also their inhibitors can correlate with
      bad prognosis of cancer patients, underlining the evolving concept of the
      protease web as the complex interplay between proteinases, their inhibitors and
      effector molecules. Elevated levels of tissue inhibitor of metalloproteinases-1
      (TIMP-1) render the liver more susceptible to metastasis by triggering urokinase
      plasminogen activator (uPA) expression as well as hepatocyte growth factor (HGF)
      signalling, thereby leading to the fatal scattered infiltration of metastasizing
      tumour cells throughout the parenchyma of the target organ. Here, we investigated
      whether host uPA is a crucial protagonist for the TIMP-1-induced modulation of a
      pro-metastatic microenvironment in the liver. Indeed, in livers of uPA-ablated
      mice elevated TIMP-1 levels did not trigger HGF signalling and did not promote
      metastasis of a murine T-lymphoma cell line. In contrast, lack of tumour cell
      derived uPA induced by gene silencing did not interfere with this pro-metastatic
      pathway. Furthermore, host uPA was necessary for the recruitment of neutrophilic
      granulocytes and the associated increase of HGF in livers with elevated TIMP-1
      levels. This newly identified co-operation between TIMP-1 and host uPA suggests
      that therapies, simultaneously interfering with pro- and anti-proteolytic
      pathways may be beneficial for patients with metastatic disease.

PMID- 19863692
TI  - Sensing, physiological effects and molecular response to elevated CO2 levels in
      eukaryotes.
AB  - Carbon dioxide (CO(2)) is an important gaseous molecule that maintains biosphere
      homeostasis and is an important cellular signalling molecule in all organisms.
      The transport of CO(2) through membranes has fundamental roles in most basic
      aspects of life in both plants and animals. There is a growing interest in
      understanding how CO(2) is transported into cells, how it is sensed by neurons
      and other cell types and in understanding the physiological and molecular
      consequences of elevated CO(2) levels (hypercapnia) at the cell and organism
      levels. Human pulmonary diseases and model organisms such as fungi, C. elegans,
      Drosophila and mice have been proven to be important in understanding of the
      mechanisms of CO(2) sensing and response.

PMID- 19863694
TI  - Lipid droplet growth by fusion: insights from freeze-fracture imaging.
AB  - An understanding of how lipid droplets grow in the cell is important to current
      human health issues. Homotypic fusion of small lipid droplets to create larger
      ones is one proposed mechanism though the evidence for this process continues to
      be debated. By applying the technique of freeze-fracture electron microscopy to
      cells that have been stimulated to accumulate lipid droplets, we here present
      images which suggest that at least some large lipid droplets may indeed result
      from amalgamation of multiple smaller ones. These visual data add significantly
      to the notion that fusion contributes to lipid droplet growth.

PMID- 19863695
TI  - Preservation of TSPO by chronic intermittent hypobaric hypoxia confers
      antiarrhythmic activity.
AB  - Abnormal activation of mitochondrial translocator protein (TSPO) contributes to
      arrhythmogenesis during cardiac metabolic compromise; however, its role in the
      antiarrhythmic activities of chronic hypoxia adaptation remains unclear. Our
      results demonstrated that 80% of normoxic rats developed ischaemic VF, whereas
      this condition was seldom observed in rats with 14 days of chronic intermittent
      hypobaric hypoxia (CIHH). TSPO stimulation or inhibition affected the arrhythmias
      incidence in normoxic rats, but did not change the CIHH-mediated antiarrhythmic
      effects. Abrupt and excessive elevation of TSPO activity was positively linked to
      ischaemic VF, and CIHH preserved TSPO activity during ischaemia. The preservation
      of TSPO activity by CIHH also contributed to the maintenance of intracellular Ca
      homeostasis. These results suggest that the blunt sensitivity of TSPO to
      ischaemic stress may be responsible for the antiarrhythmic effects by CIHH.

PMID- 19863696
TI  - Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their
      endothelial differentiation via inhibition of Akt phosphorylation.
AB  - This study was to investigate the effect of oxidized low-density lipoprotein (ox
      LDL) on the behaviour of bone marrow stem cells and their endothelial
      differentiation as well as the underlying mechanisms. Adult rat bone marrow
      multipotent progenitor cells (MAPCs) were incubated with ox-LDL for up to 2
      weeks. Ox-LDL treatment resulted in a time- and dose-dependent reduction of MAPC
      population in culture through a combination of decreased cell proliferation and
      increased apoptosis. The expression of stem cell marker Oct-4 was significantly
      suppressed in MAPCs by ox-LDL in a dose- and time-dependant manner. Endothelial
      differentiation of MAPCs was substantially inhibited by ox-LDL with markedly
      decreased expression of endothelial markers vWF, Flk-1 and CD31, as well as
      impaired in vitro vascular structure formation. Ox-LDL-induced apoptosis and
      inhibition of Oct-4 expression, cell proliferation and endothelial
      differentiation of MAPCs were associated with significant inhibition of Akt
      phosphorylation. Akt overexpression in MAPCs transfected with a constitutively
      active Akt completely reversed the effects of ox-LDL on MAPCs including enhanced
      apoptosis, decreased cell proliferation, suppressed Oct-4 expression and
      endothelial differentiation as well as in vitro vascular structure formation. In
      conclusion, ox-LDL promotes apoptosis and inhibits Oct-4 expression and self
      renewal of MAPCs, and impairs their endothelial differentiation via suppression
      of Akt signalling.

PMID- 19863697
TI  - Maternal thyroid hormones are transcriptionally active during embryo-foetal
      development: results from a novel transgenic mouse model.
AB  - Even though several studies highlighted the role of maternal thyroid hormones
      (THs) during embryo-foetal development, direct evidence of their interaction with
      embryonic thyroid receptors (TRs) is still lacking. We generated a transgenic
      mouse model ubiquitously expressing a reporter gene tracing TH action during
      development. We engineered a construct (TRE2*) containing two TH-responsive
      elements controlling the expression of the LacZ reporter gene, which encodes beta
      galactosidase (beta-gal). The specificity of the TRE2* activation by TH was
      evaluated in NIH3T3 cells by cotransfecting TRE2* along with TRs, retinoic or
      oestrogen receptors in the presence of their specific ligands. TRE2* transgene
      was microinjected into the zygotes, implanted in pseudopregnant BDF1 (a first
      generation (F1) hybrid from a cross of C57BL/6 female and a DBA/2 male) mice and
      transgenic mouse models were developed. beta-gal expression was assayed in tissue
      sections of transgenic mouse embryos at different stages of development. In
      vitro, TRE2* transactivation was observed only following physiological T3
      stimulation, mediated exclusively by TRs. In vivo, beta-gal staining, absent
      until embryonic day 9.5-10.5 (E9.5-E10.5), was observed as early as E11.5-E12.5
      in different primordia (i.e. central nervous system, sense organs, intestine,
      etc.) of the TRE2* transgenic embryos, while the foetal thyroid function (FTF)
      was still inactive. Immunohistochemistry for TRs essentially colocalized with
      beta-gal staining. No beta-gal staining was detected in embryos of hypothyroid
      transgenic mice. Importantly, treatment with T3 in hypothyroid TRE2* transgenic
      mice rescued beta-gal expression. Our results provide in vivo direct evidence
      that during embryonic life and before the onset of FTF, maternal THs are
      transcriptionally active through the action of embryonic TRs. This model may have
      clinical relevance and may be employed to design end-point assays for new
      molecules affecting THs action.

PMID- 19863698
TI  - Native LDL-induced oxidative stress in human proximal tubular cells: multiple
      players involved.
AB  - Dyslipidemia is a well-established condition proved to accelerate the progression
      of chronic kidney disease leading to tubulo-interstitial injury. However, the
      molecular aspects of the dyslipidemia-induced renal damage have not been fully
      clarified and in particular the role played by low-density lipoproteins (LDLs).
      This study aimed to examine the effects of native non-oxidized LDL on cellular
      oxidative metabolism in cultured human proximal tubular cells. By means of
      confocal microscopy imaging combined to respirometric and enzymatic assays it is
      shown that purified native LDL caused a marked increase of cellular reactive
      oxygen species (ROS) production, which was mediated by activation of NADPH
      oxidase(s) and by mitochondrial dysfunction by means of a ROS-induced ROS release
      mechanism. The LDL-dependent mitochondrial alterations comprised inhibition of
      the respiratory chain activity, enhanced ROS production, uncoupling of the
      oxidative phosphorylation efficiency, collapse of the mtDeltaPsi, increased
      Ca(2+) uptake and loss of cytochrome c. All the above LDL-induced effects were
      completely abrogated by chelating extracellular Ca(2+) as well as by inhibition
      of the Ca(2+) -activated cytoplasmic phospholipase A2, NADPH oxidase and
      mitochondrial permeability transition. We propose a mechanicistic model whereby
      the LDL-induced intracellular redox unbalance is triggered by a Ca(2+) inward
      flux-dependent commencement of cPLA2 followed by activation of a lipid- and ROS
      based cross-talking signalling pathway. This involves first oxidants production
      via the plasmamembrane NADPH oxidase and then propagates downstream to
      mitochondria eliciting redox- and Ca(2+) -dependent dysfunctions leading to cell
      harming conditions. These findings may help to clarify the mechanism of
      dyslipidemia-induced renal damage and suggest new potential targets for specific
      therapeutic strategies to prevent oxidative stress implicated in kidney diseases.

PMID- 19863699
TI  - Cytokeratin expression patterns in multiple infundibulocystic basal cell
      carcinoma.
AB  - Infundibulocystic basal cell carcinoma (IBCC) is a variant of basal cell
      carcinoma. Sporadic cases usually represent a solitary tumor and multiple IBCC is
      rare. There have been no reports in which the tumor differentiation is
      characterized immunohistochemically. We report a case of multiple IBCC which
      developed on a patient's scalp by performing histopathological and
      immunohistochemical examinations, using monoclonal antibodies against
      cytokeratins (CKs). A 76-year-old female had noticed multiple small papules on
      her scalp. She noticed that the tumors were growing when she underwent systemic
      chemotherapy for metastatic lung cancer. Routine histopathological specimens from
      skin biopsies revealed findings typical of IBCC. The tumor cells expressed CK14
      and CK17. However, CK1 and CK10 were expressed only in a few cells in the inner
      area of the tumors. The present case is unique in two points. First, multiple
      tumors developed on the patient's scalp during the systemic chemotherapy for the
      lung cancer. Second, the tumor showed CK expression patterns characteristic to
      infundibular and trichilemmal epithelia.

PMID- 19863700
TI  - C3d immunohistochemistry on formalin-fixed tissue is a valuable tool in the
      diagnosis of bullous pemphigoid of the skin.
AB  - BACKGROUND: Direct immunofluorescence (DIF) testing is an important procedure in
      the diagnosis of autoimmune bullous dermatoses. We investigated the expression of
      C3d in formalin-fixed, paraffin-embedded tissue of autoimmune bullous dermatoses.
      METHODS: The immunohistochemical expression of C3d in bullous pemphigoid (BP) (n
      = 32), pemphigoid gestationis (PG) (n = 3), pemphigus (n = 14), dermatitis
      herpetiformis Duhring (DHD) (n = 10), linear immunoglobulin A (IgA) dermatosis (n
      = 4), mixed forms of BP and linear IgA dermatosis (n = 2), and 44 controls was
      analyzed on formalin-fixed tissue. RESULTS: Thirty-one of 32 cases (97%) of BP
      and 3 out of 3 cases (100%) of PG showed a linear positivity of C3d along the
      basement membrane. Only 3 out of 14 (21%) cases of pemphigus showed an
      intraepidermal intercellular expression of C3d. The two mixed forms of linear IgA
      dermatosis and BP showed a linear positivity of C3d along the basement membrane.
      All cases of DHD, linear IgA dermatosis and all of the controls were negative for
      C3d. CONCLUSIONS: C3d immunohistochemistry is a valuable tool in the diagnosis of
      BP and PG of the skin with a sensitivity of at least 97%. Mixed forms of linear
      IgA dermatosis, and BP, DHD and linear IgA dermatosis can only be identified by
      DIF. A positive result may prompt serologic confirmation of BP without further
      need for DIF.

PMID- 19863701
TI  - Intradermal proliferative fasciitis in childhood: a potential diagnostic pitfall.
AB  - Proliferative fasciitis (PF) is a pseudosarcomatous proliferation which typically
      occurs in the subcutaneous tissue and fascia. Although patients are
      characteristically middle-aged people, occasionally PF can arise in children.
      Histologically, PF is characterized by a proliferation of large ganglion-like and
      spindle-shaped cells which, especially in childhood, may exhibit high mitotic
      activity, but no atypical mitoses. We report a case of PF in the dermis of a 13
      year-old boy. This is the first case of PF primarily arising in the dermis. Apart
      from the unusual site, another intriguing finding was the presence of rare
      atypical mitoses, a feature which has not been previously emphasized in PF.
      Awareness that PF may occur in the dermis, exhibiting occasional atypical
      mitoses, is crucial to avoid a misdiagnosis of malignancy.

PMID- 19863702
TI  - Granulomas induced by subcutaneous injection of a luteinizing hormone-releasing
      hormone analog: a case report and review of the literature.

PMID- 19863703
TI  - Myxoid intravascular fasciitis.
AB  - Nodular fasciitis is a common reactive proliferation of soft tissue. It is
      composed of high density of fibroblasts and myofibroblasts, and sometimes shows a
      sarcomatoid appearance histologically. A rare variant of nodular fasciitis,
      intravascular fasciitis can be found in the veins or arteries. Histologically,
      intravascular fasciitis has been described that resembles nodular fasciitis with
      a less prominent mucoid matrix. Here, we report a case of intravascular fasciitis
      with prominent mucin deposition. Clinically, it presented as multiple nodules on
      the leg of the patient. Histologically, it showed proliferation of spindle cells
      in a vein of the dermis and Alcian blue staining confirmed prominent mucin
      deposition between the spindle cells. Immunohistochemistry studies showed the
      spindle cells were positive for vimentin, actin and smooth muscle actin, but
      negative for keratin, S100 protein, desmin, CD31 and CD34. Based on the clinical
      and histopathological properties, a diagnosis of myxoid intravascular fasciitis
      was made.

PMID- 19863704
TI  - Daily rhythms of spike coding in the rat supraoptic nucleus.
AB  - Novel measures of coding based on interspike intervals were used to characterise
      the rhythms of single unit activity in the supraoptic nucleus during the
      day/night cycle in urethane-anaesthetised rats in vivo. Both continuously firing
      and phasic cells showed significant (P < 0.001) diurnal rhythms of spike
      frequency and in the irregularity of firing, as quantified by the log interval
      entropy (ENT). Comparison of rhythms in log interval ENT showed that the
      amplitude of the rhythms was greater for the continuously firing cells than for
      the phasic cells (P = 0.002). Rhythms persisted after hypertonic stimulation or
      pinealectomy and both treatments reduced the amplitude significantly only for the
      continuously firing cell group. By contrast, the mesor (i.e. mid-point of the
      rhythm) was reduced only for the phasic cell group. A similar analysis applied to
      the activity of cells of the suprachiasmatic nucleus showed that, after
      pinealectomy, there was a significant rhythm in ENT (P < 0.001) but not firing
      rate; however, the amplitude of the rhythm in ENT was attenuated (P = 0.047).
      Diurnal changes in the electrical activity of supraoptic cells are consistent
      with previously reported circadian changes in magnocellular neuropeptide release.
      Differences between continuous and phasic cell groups in the effects of osmotic
      stimulation on rhythmic activity indicate that the two cell types differ in their
      coding of osmolality and zeitgeber time information. The different effects of
      pinealectomy on the supraoptic and suprachiasmatic nuclei suggest that removal of
      endogenous melatonin unmasks a difference in circadian coding between the two
      nuclei.

PMID- 19863705
TI  - The impact of ear, nose and throat surgery on children's subsequent use of health
      services: An 8-year cohort study.
AB  - AIM: High rates of paediatric ear, nose and throat (ENT) surgery persist. Little
      is known about its impact on health service utilisation. This study investigated
      whether children who had ENT surgery used more health services prior to surgery
      (excluding the perisurgery period), and, if so, whether surgery resulted in
      reduced utilisation. METHODS: A retrospective population cohort study of health
      services use (measured by Medicare claims) by 6239 New South Wales children from
      the time of their birth in January 1990 until December 1997. We compared: (i)
      number of claims during the 8-year period for the 359 children who had privately
      funded ENT surgery (tonsillectomy, myringotomy or adenoidectomy) with claims made
      by 5880 children who did not have ENT surgery; and (ii) among children who had
      surgery: we compared claims made before surgery with those made after surgery.
      RESULTS: Children who had privately funded ENT surgery (comprising 59% of all
      paediatric ENT surgery) used significantly more services than other children in
      total (103.8 claims vs. 57.1 over 8 years) and in each three months of age from
      birth to eight years, including services for non-ENT-related conditions.
      Tonsillectomy resulted in a decline in claims, but not to the level of children
      who did not have surgery. Most children who had myringotomy continued high-level
      health services use following surgery. CONCLUSIONS: High volume health services
      utilisation is a potential predictor of ENT surgery in this population. These
      results suggest a need to investigate non-clinical factors that influence service
      utilisation, which may include higher parental expectations or anxiety regarding
      their children's health.

PMID- 19863706
TI  - Angiotensin-converting enzyme gene insertion/deletion polymorphism frequency in
      normotensive children with a positive family history of essential hypertension.
AB  - AIM: To evaluate the possible relationship between blood pressure (BP) and
      angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in
      normotensive children with a positive family history of essential hypertension
      (EHT). MATERIAL AND METHODS: Three hundred seventy-six randomly selected
      normotensive schoolchildren (147 boys, 229 girls) between the ages of seven and
      17 years were enrolled. Children were subdivided into a 'first-degree relative
      group' and a 'second-degree relative group' according to the presence of EHT in
      parents or grandparents, respectively. BP was measured twice from the right arm
      and the systolic BP, diastolic BP and mean BP were recorded. ACE gene I/D
      polymorphism was performed from all studied children and frequency od DD, ID and
      ID allele were analysed in each study group. RESULTS: Allelic frequencies of the
      DD genotype of the ACE gene were higher in children with a positive history in
      the first- (36.2%) and second-degree (38.3%) relatives for EHT than the controls
      (30.7%) (P < 0.05 for both). Children with a positive family history of EHT and a
      DD genotype, had significantly higher SBP, DBP and MBP levels (P < 0.05) than the
      children with ID or II genotypes. CONCLUSION: We found that the ACE gene DD
      genotype was common and that BP levels were higher in Turkish children with a
      positive family history of EHT and DD genotype. Because the presence of DD allele
      might be the one of the potential contributor of EHT pathogenesis, further
      studies needed in large cohort for long term follow-up for EHT in children with
      DD allele.

PMID- 19863707
TI  - Family functioning at meals relates to adherence in young children with type 1
      diabetes.
AB  - AIMS: This study examined associations between mealtime family functioning,
      dietary adherence and glycaemic control in young children with type 1 diabetes
      mellitus (T1DM). We hypothesised that poorer family functioning would correlate
      with poorer dietary adherence and glycaemic control. METHODS: Thirty-five
      families of children (M = 5.6 +/- 1.5 years) with T1DM had meals videotaped in
      their home, which were coded for family functioning according to the McMaster
      Interaction Coding System. Children's dietary adherence was assessed according to
      deviations from the prescribed number of carbohydrate units per meal and
      recommended carbohydrate intake levels per day. Glycaemic control was measured
      via 14 days of self-monitoring of blood glucose levels. RESULTS: Findings
      demonstrated significant negative associations between children's dietary
      adherence and two dimensions of family functioning: Task Accomplishment (r=-0.43,
      P= 0.03) and Behavioral Control (r=-0.54, P= 0.00). Affect Management correlated
      negatively with the percent of blood glucose levels below the normal range (r=
      0.33, P= 0.05). Eleven families (31%) of young children with type 1 diabetes
      demonstrated mealtime family functioning in the unhealthy range. CONCLUSIONS:
      This was the first study to examine the relationship between mealtime family
      functioning and children's dietary adherence and glycaemic control in families of
      young children with T1DM. Previous research has found mealtime family functioning
      to be impaired in families of young children with T1DM when compared with
      families of children without diabetes. Research is needed to determine if family
      functioning and dietary adherence can be improved via specific family-based
      behavioural training around mealtimes.

PMID- 19863708
TI  - Ten years of pneumococcal-associated haemolytic uraemic syndrome in New Zealand
      children.
AB  - AIM: To describe the epidemiology, clinical features, management and outcome of
      pneumococcal-associated haemolytic-uraemic syndrome (P-HUS) in New Zealand over
      the past decade. METHODS: A retrospective chart review of children with P-HUS
      from 1998 to 2007 that were prospectively reported to the New Zealand Paediatric
      Surveillance Unit. P-HUS was defined as microangiopathic haemolytic anaemia (Hb
      <100 g/L with fragmented red blood cells), thrombocytopaenia (platelet count <130
      x 10(9)/L), acute renal impairment with oliguria and elevated plasma creatinine,
      and confirmed or suspected pneumococcal infection. RESULTS: Eleven children (nine
      male, two female), predominately Maori and Polynesian (10 children) were studied.
      The median age was 8.5 months. The median duration of hospitalisation was 25
      days. Of the infections, 10 were confirmed pneumococcal (six pneumonia, four
      meningitis) and one pneumonia was suspected pneumococcal (culture negative,
      however T activation positive). Nine patients required dialysis for a median
      duration of 13 days. One child with meningitis died after therapy was withdrawn
      because of severe neurological injury. One patient developed end stage kidney
      disease and two further children had evidence of persisting renal sequelae at
      follow-up. CONCLUSIONS: Pneumococcal disease remains an important public health
      problem in New Zealand children, particularly those of Maori and Pacific Island
      ethnicity. P-HUS should be considered in pneumococcal disease associated with
      severe haematological and renal abnormalities. These children should be monitored
      long-term, as they are at risk of permanent renal injury.

PMID- 19863709
TI  - Teaching paediatric epilepsy to medical students: A randomised crossover trial.
AB  - AIM: Research has shown computerised tutorial to be as effective as face-to-face
      teaching in promoting knowledge acquisition. Subsequently, the clinician must
      synthesise and interpret data (clinical reasoning). This study extends previous
      research and compares the effectiveness of interactive lecture and computerised
      tutorial in promoting observational skills and clinical reasoning in the
      evaluation of paroxysmal events. METHODS: The modalities were compared through a
      randomised crossover trial teaching epilepsy to third and fourth year medical
      students. The content matter (history and video clip) and format were identical
      for each topic (Topic 1: altered awareness, Topic 2: movement and posturing) in
      both modalities (interactive lecture and computerised tutorial). Structured
      worksheets promoted and evaluated skills of observation and clinical reasoning.
      Responses in both domains were compared with gold standard qualitative scores.
      Participants rated modality preference and perceptions of teaching. RESULTS: One
      hundred and fifty-seven medical students participated. Interactive lecture and
      computerised tutorial were both effective in promoting observational skills and
      clinical reasoning with no differences between modalities. Participants preferred
      the interactive lecture and rated it more enjoyable and effective. Twenty-five
      participants randomised to the computerised tutorial for Topic 1, elected to
      withdraw participation. Both modalities promoted interest and willingness to
      further learn. CONCLUSION: This is the first randomised crossover trial
      evaluating the teaching of clinical reasoning in comparative medical education
      research. Interactive lecturing and computerised tutorial were both effective in
      teaching observational skills and clinical reasoning. Interactive lecture is the
      preferred method, and may influence initial engagement in learning.

PMID- 19863710
TI  - Continuous intrathecal baclofen for children with spasticity and/or dystonia:
      Goal attainment and complications associated with treatment.
AB  - AIM: To describe complications and outcomes of intrathecal baclofen (ITB) therapy
      in children with spasticity and/or dystonia. METHODS: A prospective study of goal
      attainment after ITB therapy and a retrospective review of medical records for
      complications. The children were described as dystonia-predominant or spasticity
      predominant and the subgroups were compared. Goals were assessed at baseline and
      goal attainment at 6 months post-implant. Data were analysed using Wilcoxon
      signed-rank test. The patients' goals were measured with the Canadian
      Occupational Performance Measure (COPM) and goal attainment scaling (GAS).
      Complication rates were calculated by dividing the number of complications by the
      duration of pump implantation. RESULTS: Twenty-five children were included, 16
      with complete goal attainment data. The mean age was 10 years and 3 months.
      Eighty-eight percent had a diagnosis of cerebral palsy. The most common goals
      were improved positioning and transfers. A statistically significant increase (P
      < 0.001) in both domains of the COPM was demonstrated. The mean GAS T-score was
      significantly higher at 6 months post implant (P < 0.001). Seventy percent of the
      subjects achieved their goals at 6 months. The complication rate was 0.38 per
      year of pump operation, higher in subjects with dystonia (0.71) compared with
      those with spasticity (0.25). CONCLUSIONS: ITB results in statistically
      significant levels of satisfaction and goal attainment in children with
      spasticity and/or dystonia. GAS was a useful measure of goal attainment. While,
      ITB is effective for children with spasticity and dystonia, those with dystonia
      have a higher rate of complications.

PMID- 19863711
TI  - Adolescent and young adult health in a children's hospital: Everybody's business.
AB  - BACKGROUND: To guide the development of adolescent health training and the
      planning of future services, accurate data describing health service use by
      adolescents and young adults are needed. AIM: To describe admission rates for
      adolescents (12-17 years) and young adults (age 18 years and over) attending a
      specialist children's hospital over an 8-year period. Specific objectives were to
      describe the (i) proportion of adolescents and young adults admitted under
      different specialties; (ii) age range, with emphasis on those 18 years and over;
      and (iii) proportion of patients admitted to the general adolescent ward.
      METHODS: Data on adolescent and young adult admissions to Princess Margaret
      Hospital (PMH) were collected prospectively from July 2000 to June 2008. RESULTS:
      Adolescents and young adults accounted for one fifth (range 18-22%) of all
      admissions to PMH. Over the 8-year period, the number of adolescent and young
      adult admissions increased from 3935 (54% males) to 4967 (56% males) per year.
      The proportion admitted to the general adolescent ward ranged from 22% to 36%.
      The three specialties admitting the most adolescents and young adults were
      General Surgery (11-13%), Orthopaedics (11-13%) and Oncology/Haematology (10
      14%). The age range was: 12-14 years (57-67%); 15-17 (30-39%); 18+ (2-5%). At
      least 15 patients aged 20 or over were admitted each year, mostly for Dental or
      Plastic Surgery. CONCLUSIONS: Adolescent and young adult health is part of the
      core business of paediatrics. This should be reflected in the planning of future
      paediatric services. All trainees require some basic training, regardless of heir
      specialty area.

PMID- 19863712
TI  - A survey of the management of neonatal hypoglycaemia within the Australian and
      New Zealand Neonatal Network.
AB  - BACKGROUND: Neonatal hypoglycaemia is a common problem linked to both brain
      damage and death. There is controversy regarding both the definition of and best
      treatment for neonatal hypoglycaemia. AIM: To determine current management of
      neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network
      (ANZNN). METHODS: Four questionnaires were sent to the Director of each of the 45
      nurseries within the ANZNN. The Director was asked to complete one questionnaire
      and give the remaining three to other doctors involved with the management of
      babies with hypoglycaemia in the nursery. RESULTS: One hundred and eighty surveys
      were sent and 127 were returned (71%), including at least one from each nursery.
      Almost all respondents (120, 94%) reported using a protocol to treat
      hypoglycaemia. Only 2 (2%) reported screening all babies for neonatal
      hypoglycaemia, with the remainder screening babies at risk. Only 67, (53%)
      reported that blood glucose levels were tested on an analyser generally
      considered to be reliable at low levels. Most respondents (99, 78%) reported the
      clinical threshold for treatment was <2.6 mmol/L. However, when provided with
      clinical scenarios, respondents reported a variety of interventions, including no
      treatment. CONCLUSION: Doctors within the ANZNN are consistent about definition
      and screening for neonatal hypoglycaemia. However, frequently, the diagnosis is
      made using unreliable analysers. There is also wide variation in treatment,
      suggesting a lack of reliable evidence on which to base practice.

PMID- 19863714
TI  - Joining the dots: The links between education and health and implications for
      indigenous children.
AB  - This paper provides a general overview of the literature investigating the nexus
      between education and health; discussing the relationship between these domains
      at individual, family and community levels. We then briefly examine the programme
      and research implications of such a framework for interventions aimed at
      improving education and health, with specific reference to young Indigenous
      Australians. We find that while education and health are inextricably linked,
      throughout the life course and at different levels of influence, there is less
      empirical work exploring this relationship in an Indigenous context. Given the
      gravity of literacy and numeracy failure rates in school-based education and its
      potential impact on Indigenous health, we assert an urgent case for rigorous
      research into interventions that address the barriers to effectiveness in
      implementing quality educational experiences and opportunities for Indigenous
      children.

PMID- 19863713
TI  - What research questions matter to Australian paediatricians? National Delphi
      Study.
AB  - AIM: The newly formed Australian Paediatric Research Network (APRN) aims to
      facilitate general paediatricians' participation in research in secondary care
      settings. This (its first) project aimed to identify Australian paediatricians'
      top research priorities and preferred research designs. METHODS: All Australian
      general paediatricians were invited into a national Delphi process survey. In
      Stage 1, they were asked 'Thinking about your clinical practice, what are the
      most important research questions which need addressing?'. Using qualitative
      methods, a 'top 20' list of the most common, feasible research questions was
      generated. In Stage 2, respondents prioritised these 'top 20' research questions
      in terms of perceived importance to their practice, and rated their interest in
      participating in various types of research. RESULTS: A total of 685 (68%) of 1006
      paediatricians completed the baseline survey, with 209 paediatricians
      contributing 430 Stage 1 research questions. Of these, 128 (30%) had not been
      addressed in the literature and were researchable in the secondary care
      outpatient setting. The top five questions ranked in Stage 2 by 348
      paediatricians were obesity management (two questions), long-term ADHD
      educational outcomes, autism spectrum outcomes, and prophylactic antibiotics in
      preventing urinary tract infections. Paediatricians were willing to participate
      in research designs, including longitudinal research (75%) and randomised trials
      (64%). CONCLUSIONS: Australian paediatricians are interested in research, and
      their ideas can provide direction for APRN and potentially other networks in
      Australia. Many of the questions generated could not be easily answered by
      traditional biomedical and clinical research methods, highlighting the potential
      benefit of practice-based research networks.

PMID- 19863715
TI  - A comparison of single-sample effective size estimators using empirical toad
      (Bufo calamita) population data: genetic compensation and population size-genetic
      diversity correlations.
AB  - The accuracy and precision of four single-sample estimators of effective
      population size, N(e) (heterozygote excess, linkage disequilibrium, Bayesian
      partial likelihood and sibship analysis) were compared using empirical data
      (microsatellite genotypes) from multiple natterjack toad (Bufo calamita)
      populations in Britain (n = 16) and elsewhere in Europe (n = 10). Census size
      data were available for the British populations. Because toads have overlapping
      generations, all of these methods estimated the number of effective breeders N(b)
      rather than N(e). The heterozygote excess method only provided results, without
      confidence limits, for nine of the British populations. Linkage disequilibrium
      gave estimates for 10 British populations, but only six had finite confidence
      limits. The Bayesian and sibship methods both produced estimates with finite
      confidence limits for all the populations. Although the Bayesian method was the
      most precise, on most criteria (insensitivity to locus number, correlation with
      other effective and census size estimates and correlation with genetic diversity)
      the sibship method performed best. The results also provided evidence of genetic
      compensation in natterjack toads, and highlighted how the relationship between
      effective size and genetic diversity can vary as a function of geographical
      scale.

PMID- 19863716
TI  - Plant chemical defence allocation constrains evolution of local range.
AB  - Many species of plants in the wild are distributed spatially in patches, the
      boundaries of which may occur and change because of a complicated interplay
      between myriad environmental stressors and limitations of, or constraints on,
      plant coping mechanisms. By examining genetic variation and co-variation among
      marker-inferred inbred lines and sib-families of an upland wild mustard species
      within and just a few meters across a natural patch boundary, we show that the
      evolution of tolerance to the stressful environment outside the patch may be
      constrained by allocation to glucosinolate compounds (GS) that are defensive
      against generalist insect herbivores. Several potential stressors were associated
      with the patch boundary, but carbon isotope ratios indicated that sib-families
      with smaller stomatal apertures maintained performance better in response to late
      season dry conditions, suggesting that drought was an important stressor. The
      presence of GS may help explain the characteristic patchy distribution of
      mustards, a relatively diverse and important plant family. This result challenges
      one end of the continuum of the long-standing Plant Apparency hypothesis, which
      essentially states the opposite causation, that low molecular weight toxins like
      GS are evolutionary responses of patchy distributions and correlated life-history
      traits.

PMID- 19863717
TI  - The effect of marker choice on estimated levels of introgression across an avian
      (Pipridae: Manacus) hybrid zone.
AB  - Hybrid zones are often characterized by narrow, coincident clines for diverse
      traits, suggesting that little introgression occurs across them. However, this
      pattern may result from a bias in focussing on traits that are diagnostic of
      parental populations. Such choice of highly differentiated traits may cause us to
      overlook differential introgression in nondiagnostic traits and to distort our
      perception of hybrid zones. We tested this hypothesis in an avian hybrid zone by
      comparing cline structure in two sets of molecular markers: isozyme and
      restriction fragment length polymorphism markers chosen for differentiation
      between parental forms, and microsatellite markers chosen for polymorphism. Two
      cline-fitting methods showed that cline centre positions of microsatellite
      alleles were more variable than those of isozyme and restriction fragment length
      polymorphism markers, and several were significantly shifted from those of the
      diagnostic markers. Cline widths of microsatellite alleles were also variable and
      two- to eightfold wider than those of the diagnostic markers. These patterns are
      consistent with the idea that markers chosen for differentiation are more likely
      to be under purifying selection, and studies focussed on these markers will
      underestimate overall introgression across hybrid zones. Our results suggest that
      neutral and positively selected alleles may introgress freely across many hybrid
      zones without altering perceived boundaries between hybridizing forms.

PMID- 19863718
TI  - Source-sink dynamics structure a common montane mammal.
AB  - Assessing the relative role of evolutionary processes on genetic diversity is
      critical for understanding species response to climatic change. However, many
      processes, independent of climate, can lead to the same genetic pattern. Because
      effective population size and gene flow are affected directly by abundance and
      dispersal, population ecology has the potential to profoundly influence patterns
      of genetic variation over microevolutionary timescales. Here, we use aDNA data
      and simulations to explore the influence of population ecology and Holocene
      climate change on genetic diversity of the Uinta ground squirrel (Spermophilus
      armatus). We examined phylochronology from three modern and two ancient
      populations spanning the climate transitions of the last 3000 years. Population
      genetic analyses based on summary statistics suggest that changes in genetic
      diversity and structure coincided with the Medieval Warm Period (MWP), c. 1000
      years ago. Serial coalescent simulations allowed us to move beyond correlation
      with climate to statistically compare the likelihoods of alternative population
      histories given the observed data. The data best fit source-sink models that
      include large, mid-elevation populations that exchange many migrants and small
      populations at the elevational extremes. While the MWP is likely to have reduced
      genetic diversity, our model-testing approach revealed that MWP-driven changes in
      genetic structure were not better supported for the range of models explored. Our
      results point to the importance of species ecology in understanding responses to
      climate, and showcase the use of ancient genetic data and simulation-based
      inference for unraveling the relative roles of microevolutionary processes.

PMID- 19863719
TI  - Hybridization involving independent gametophytes in the Vandenboschia radicans
      complex (Hymenophyllaceae): a new perspective on the distribution of fern
      hybrids.
AB  - To test our hypothesis of hybrid formation involving the 'independent
      gametophyte' phenomenon in ferns, we identified the genomic formulae and ploidy
      level of gametophytes of the Vandenboschia radicans complex at the periphery of a
      sporophyte population. We identified haploid gametophytes of V. kalamocarpa (one
      of the two putative parents of V.xstenosiphon) in a hybrid sporophyte population
      in Japan that lacks fertile non-hybrid individuals. Furthermore, diploid
      sporophytes of the species were not found within a 50-km radius. This finding
      supports a hypothesis of hybridization involving the 'independent gametophyte'
      phenomenon and provides a new perspective on the geographical distribution of
      fern hybrids.

PMID- 19863720
TI  - Contrasting signals from multiple markers illuminate population connectivity in a
      marine fish.
AB  - Recent advances in molecular biology and bioinformatics have helped to unveil
      striking and previously unrecognized patterns of geographic genetic structure in
      marine populations. Largely driven by the pressing needs of fisheries management
      and conservation, studies on marine fish populations have played a pivotal role
      in testing the efficiency of a range of approaches to explore connectivity and
      dispersal at sea. Here, we employed nuclear and mitochondrial DNA markers and
      parasitic infestations to examine the nature and patterns of population structure
      in a warm-temperate coastal marine teleost across major putative biogeographic
      barriers in the Mediterranean Sea and Eastern Atlantic Ocean. We detected deep
      genetic divergence between mitochondrial lineages, likely caused by dramatic
      climatic and geological transformations before and during the Pleistocene. Such
      long-diverged lineages later came into secondary contact and can now be found in
      sympatry. More importantly, microsatellite data revealed that these lineages,
      after millions of years of independent evolution, now interbreed extensively. By
      combining genetic and parasite data, we were able to identify at least five
      independent demographic units. While the different genetic and parasite-based
      methods produce notably contrasting signals and may complicate the reconstruction
      of connectivity dynamics, we show that by tailoring the correct interpretation to
      each of the descriptors used, it is possible to achieve a deeper understanding of
      the micro-evolutionary process and, consequently, resolve population structure.

PMID- 19863721
TI  - Genetic diversity and phylogeography in two diploid ferns, Asplenium fontanum
      subsp. fontanum and A. petrarchae subsp. bivalens, in the western Mediterranean.
AB  - Asplenium fontanum subsp. fontanum and A. petrarchae subsp. bivalens are diploid
      rock ferns of limestone outcrops of the western Mediterranean region. Asplenium
      fontanum subsp. fontanum occurs from Valencia through northeastern Spain to the
      Alpes-Maritimes and Swiss Jura. Asplenium petrarchae subsp. bivalens occurs only
      on Majorca, in Valencia and possibly in southern Spain. We analysed allozyme and
      chloroplast genetic marker diversity in 75 populations of A. fontanum subsp.
      fontanum and 12 populations of A. petrarchae subsp. bivalens sampled from across
      their respective ranges. The two species show similar levels of species and
      population genetic diversity to one another and to other diploid European
      Asplenium taxa. Both are predominantly outbreeding, as indicated by F(IS) = 0.108
      and 0.167 respectively. Substantial between-population differentiation results
      largely from differentiation between regions. Isolation by distance operates over
      limited geographic ranges, up to 50 km. In A. fontanum subsp. fontanum, the major
      geographical differentiation between Valencia and the rest of the taxon range
      probably represents an ancient range fragmentation. A less pronounced
      differentiation divides populations in the SW from those in the NE of the range,
      with evidence for a biogeographic link between the eastern Pyrenees and
      southeastern France. High diversity in the Pyrenees may either represent ancient
      population differentiation, or a suture zone. In A. petrarchae subsp. bivalens,
      populations on Majorca exhibit a subset of the genetic diversity present in
      Valencia, although the two regions are strongly differentiated by differing
      allele frequencies. Dispersal from the mainland may have founded Majorcan
      populations, although a role for in situ island survival cannot be excluded.

PMID- 19863722
TI  - Parents' genetic dissimilarity and offspring sex in a polygynous mammal.
AB  - Offspring quality may benefit from genetic dissimilarity between parents.
      However, genetic dissimilarity may trade-off with additive genetic benefits. We
      hypothesized that when sexual selection produces sex-specific selective
      scenarios, the relative benefits of additive genetic vs. dissimilarity may differ
      for sons and daughters. Here we study a sample of 666 red deer (Cervus elaphus)
      microsatellite genotypes, including males, females and their foetuses, from 20
      wild populations in Spain (the main analyses are based on 241 different foetuses
      and 190 mother-foetus pairs). We found that parental lineages were more
      dissimilar in daughters than in sons. On average, every mother was less related
      to her mate than to the sample of fathers in the population when producing
      daughters not sons. Male foetuses conceived early in the rutting season were much
      more inbred than any other foetuses. These differences maintained through
      gestation length, ruling out intrauterine mortality as a cause for the results,
      and indicating that the potential mechanism producing the association between
      parents' dissimilarity and offspring sex should operate close to mating or
      conception time. Our findings highlight the relevance of considering the sex of
      offspring when studying genetic similarity between parents.

PMID- 19863723
TI  - Multiple losses of self-incompatibility in North-American Arabidopsis lyrata?:
      phylogeographic context and population genetic consequences.
AB  - Arabidopsis lyrata is mostly outcrossing due to a sporophytic self
      incompatibility (SI) system but around the Great Lakes of North America some
      populations have experienced a loss of SI. We researched the loss of SI in a
      phylogeographic context. We used cpDNA and microsatellite markers to test if
      populations of North-American A. lyrata around the Great Lakes have experienced
      different (recent) histories, and linked this with individually established
      selfing phenotype and population level realized outcrossing rates calculated
      based on variation in progeny arrays at multi-locus microsatellite markers. We
      found three chloroplast haplotypes, in two of which the loss of self
      incompatibility had occurred independently. Shifts to high rates of inbreeding
      were most apparent in one of these lineages but individuals showing loss of SI
      occurred in all three. Self-compatible individuals usually showed a reduction of
      observed heterozygosity (H(O)) compared to outcrossing individuals. In the
      lineage that included the populations with the highest levels of inbreeding, this
      reduction was more substantial. This may indicate that the loss of SI in this
      lineage did not occur as recently as in the other lineage. The geographic
      distribution of the haplotypes suggested that there had been at least two
      independent colonization routes to the north of the Great Lakes following the
      last glaciation. This is consistent with postglacial migration patterns that have
      been suggested for other organisms with limited dispersal, such as reptiles and
      amphibians.

PMID- 19863724
TI  - Mueller-Hinton methylene blue media as an alternative to RPMI 1640 for
      determining the susceptibility of Cryptococcus neoformans and Cryptococcus gattii
      to posaconazole with Etest.
AB  - Mueller-Hinton modified agar (MH-GMB) was compared with RPMI + 2% glucose-agar to
      determine the MICs of 80 isolates of Cryptococcus neoformans and C. gattii to
      posaconazole with Etest. MH-GMB minimised trailing and agreement between both
      media was 94%. Agreement of M27-A2 microbroth reference method was 98% with RPMI
      and 94% with MB-GMB.

PMID- 19863725
TI  - Prevalence of tinea capitis in Southeastern Austria between 1985 and 2008: up-to
      date picture of the current situation.
AB  - Tinea capitis is the most common dermatophyte infection in childhood, but may
      rarely occur in adults and the elderly. Causative agents vary within different
      geographical areas as well as during decades. The aim of this study was to
      evaluate the prevalence and causative agents of tinea capitis in Southeastern
      Austria. Retrospective analysis of 714 patients diagnosed with tinea capitis seen
      at the outpatient Department of Dermatology/Medical University of Graz during the
      time period 1985-2008 was carried out. A total of 517 of the 714 patients were
      children, 21 adults and in the case of 176 patients age was not available.
      Microsporum canis was found in 84.4%. Trichophyton soudanense tinea capitis is
      seen since 1998, Trichophyton tonsurans for the first time in 2008. Tinea capitis
      has become very important for the public health. Besides an increasing incidence,
      there is a change in age of the patients affected and with the pattern of
      causative agents as a result of immigration movements and lifestyle habits mainly
      influenced by domestic pets. Our situation reflects nearly the epidemiology of
      the bordering countries of Austria mainly in the Southeastern surroundings. These
      epidemiological changes are a challenge for general practitioners, dermatologists
      and veterinarians to work close together for advice on control, early diagnosing
      and adequate treatment.

PMID- 19863726
TI  - How does moss photosynthesis relate to leaf and canopy structure? Trait
      relationships for 10 Hawaiian species of contrasting light habitats.
AB  - Mosses are an understudied group of plants that can potentially confirm or expand
      principles of plant function described for tracheophytes, from which they diverge
      strongly in structure. We quantified 35 physiological and morphological traits
      from cell-, leaf- and canopy-level, for 10 ground-, trunk- and branch-dwelling
      Hawaiian species. We hypothesized that trait values would reflect the distinctive
      growth form and slow growth of mosses, but also that trait correlations would be
      analogous to those of tracheophytes. The moss species had low leaf mass per area
      and low gas exchange rate. Unlike for tracheophytes, light-saturated
      photosynthetic rate per mass (A(mass)) did not correlate with habitat irradiance.
      Other photosynthetic parameters and structural traits were aligned with
      microhabitat irradiance, driving an inter-correlation of traits including leaf
      area, cell size, cell wall thickness, and canopy density. In addition, we found a
      coordination of traits linked with structural allocation, including costa size,
      canopy height and A(mass). Across species, A(mass) and nitrogen concentration
      correlated negatively with canopy mass per area, analogous to linkages found for
      the 'leaf economic spectrum', with canopy mass per area replacing leaf mass per
      area. Despite divergence of mosses and tracheophytes in leaf size and function,
      analogous trait coordination has arisen during ecological differentiation.

PMID- 19863727
TI  - Molecular trait indicators: moving beyond phylogeny in arbuscular mycorrhizal
      ecology.
AB  - Arbuscular mycorrhizal (AM) fungi form symbiotic associations with the roots of
      most plants, thereby mediating nutrient and carbon fluxes, plant performance, and
      ecosystem dynamics. Although considerable effort has been expended to understand
      the keystone ecological position of AM symbioses, most studies have been limited
      in scope to recording organism occurrences and identities, as determined from
      morphological characters and (mainly) ribosomal sequence markers. In order to
      overcome these restrictions and circumvent the shortcomings of culture- and
      phylogeny-based approaches, we propose a shift toward plant and fungal protein
      encoding genes as more immediate indicators of mycorrhizal contributions to
      ecological processes. A number of candidate target genes, involved in the uptake
      of phosphorus and nitrogen, carbon cycling, and overall metabolic activity, are
      proposed. We discuss the advantages and disadvantages of future protein-encoding
      gene marker and current (phylo-) taxonomic approaches for studying the impact of
      AM fungi on plant growth and ecosystem functioning. Approaches based on protein
      encoding genes are expected to open opportunities to advance the mechanistic
      understanding of ecological roles of mycorrhizas in natural and managed
      ecosystems.

PMID- 19863728
TI  - The evolution of the land plant life cycle.
AB  - The extant land plants are unique among the monophyletic clade of photosynthetic
      eukaryotes, which consists of the green algae (chlorophytes), the charophycean
      algae (charophytes), numerous groups of unicellular algae (prasinophytes) and the
      embryophytes, by possessing, firstly, a sexual life cycle characterized by an
      alternation between a haploid, gametophytic and a diploid, sporophytic
      multicellular generation; secondly, the formation of egg cells within
      multicellular structures called archegonia; and, thirdly, the retention of the
      zygote and diploid sporophyte embryo within the archegonium. We review the
      developmental, paleobotanical and molecular evidence indicating that: the
      embryophytes descended from a charophyte-like ancestor; this common ancestor had
      a life cycle with only a haploid multicellular generation; and the most ancient
      (c. 410 Myr old) land plants (e.g. Cooksonia, Rhynia and Zosterophyllum) had a
      dimorphic life cycle (i.e. their haploid and diploid generations were
      morphologically different). On the basis of these findings, we suggest that the
      multicellular reproductive structures of extant charophytes and embryophytes are
      developmentally homologous, and that those of the embryophytes evolved by virtue
      of the co-option and re-deployment of ancient algal homeodomain gene networks.

PMID- 19863729
TI  - Acclimation of Trichodesmium erythraeum ISM101 to high and low irradiance
      analysed on the physiological, biophysical and biochemical level.
AB  - As the nonheterocystous diazotrophic cyanobacterium Trichodesmium lives both at
      the ocean surface and deep in the water column, it has to acclimate to vastly
      different irradiances. Here, we investigate its strategy of light acclimation in
      several ways. In this study, we used spectrally resolved fluorescence kinetic
      microscopy to investigate the biophysics of photosynthesis in individual cells,
      analysed cell extracts for pigment and phycobiliprotein composition, measured
      nitrogenase activity and the abundance of key proteins, and assayed protein
      synthesis/degradation by radioactive labelling. After acclimation to high light,
      Trichodesmium grew faster at 1000 micromol m(-2) s(-1) than at 100 micromol m(-2)
      s(-1). This acclimation was associated with decreasing cell diameter, faster
      protein turnover, the down-regulation of light-harvesting pigments and the outer
      part of the phycobiliprotein antenna, the up-regulation of light-protective
      carotenoids, changes in the coupling of phycobilisomes to the reaction centres
      and in the coupling of individual phycobiliproteins to the phycobilisomes. The
      latter was particularly interesting, as it represents an as yet unreported light
      acclimation strategy. Only in the low light-acclimated culture and only after the
      onset of actinic light did phycourobilin and phycoerythrin contribute to
      photochemical fluorescence quenching, showing that these phycobiliproteins may
      become quickly (in seconds) very closely coupled to photosystem II. This fast
      reversible coupling also became visible in the nonphotochemical changes of the
      fluorescence quantum yield.

PMID- 19863730
TI  - Photoprotection of reaction centres in photosynthetic organisms: mechanisms of
      thermal energy dissipation in desiccated thalli of the lichen Lobaria pulmonaria.
AB  - *The photobionts of lichens have previously been shown to reversibly inactivate
      their photosystem II (PSII) upon desiccation, presumably as a photoprotective
      mechanism. The mechanism and the consequences of this process have been
      investigated in the green algal lichen Lobaria pulmonaria. *Lichen thalli were
      collected from a shaded and a sun-exposed site. The activation of PSII was
      followed by chlorophyll fluorescence measurements. *Inactivation of PSII, as
      indicated by the total loss of variable fluorescence, was accompanied by a strong
      decrease of basal fluorescence (F(0)). Sun-grown thalli, as well as thalli
      exposed to low irradiance during drying, showed a larger reduction of F(0) than
      shade-grown thalli or thalli desiccated in the dark. Desiccation increased
      phototolerance, which was positively correlated to enhanced quenching of F(0).
      Quenching of F(0) could be reversed by heating, and could be inhibited by
      glutaraldehyde but not by the uncoupler nigericin. *Activation of energy
      dissipation, apparent as F(0) quenching, is proposed to be based on an alteration
      in the conformation of a pigment protein complex. This permits thermal energy
      dissipation and gives considerable flexibility to photoprotection. Zeaxanthin
      formation apparently did not contribute to the enhancement of photoprotection by
      desiccation in the light. Light-induced absorbance changes indicated the
      involvement of chlorophyll and carotenoid cation radicals.

PMID- 19863731
TI  - Extensive coupling of alternative splicing of pre-mRNAs of serine/arginine (SR)
      genes with nonsense-mediated decay.
AB  - In Arabidopsis, pre-mRNAs encoding serine/arginine (SR) proteins, key regulators
      of constitutive and alternative splicing, are extensively alternatively spliced.
      In seedlings, 13 SR genes are alternatively spliced to generate 75 transcripts,
      of which 53 contain a premature termination codon (PTC). However, it is not known
      if any of the PTC-containing splice variants are the targets of nonsense-mediated
      decay (NMD) and if there is any link between NMD and the abundance of functional
      transcripts. Here, we analyzed the abundances of all splice variants for each
      alternatively spliced gene in an Arabidopsis mutant that lacks UPF3, one of the
      core components of NMD machinery, to determine if the PTC-containing transcripts
      are degraded by NMD. Our results show that about half of the 53 splice variants
      with a PTC are the targets of degradation by NMD. The accumulation of PTC
      containing transcripts resulted in concomitant reduction in the amount of
      functional transcript. These results show widespread coupling of alternative
      splicing with NMD in the SR gene family, suggesting a strong link between
      unproductive splicing and the abundance of functional transcripts.

PMID- 19863732
TI  - Variability of zinc tolerance among and within populations of the
      pseudometallophyte species Arabidopsis halleri and possible role of directional
      selection.
AB  - We estimated the level of quantitative polymorphism for zinc (Zn) tolerance in
      neighboring metallicolous and nonmetallicolous populations of Arabidopsis halleri
      and tested the hypothesis that divergent selection has shaped this polymorphism.
      A short-term hydroponic test was used to capture the quantitative polymorphism
      present between edaphic types, among and within populations. We measured six
      morphological and physiological traits on shoots and roots to estimate the
      response of A. halleri to Zn. In order to assess the adaptive value of Zn
      tolerance polymorphism, we compared differentiation of quantitative traits with
      that of molecular markers. Zinc tolerance of metallicolous populations was, on
      average, higher than that of nonmetallicolous populations according to the
      morphological and physiological traits measured. Phenotypic variability within
      edaphic types was very high and mainly explained by polymorphism among
      individuals within populations. Genetic differentiation for photosystem II yield
      of leaves (a measure of photosynthetic efficiency) was greater than the
      differentiation for microsatellite and thus, probably shaped by divergent
      selection. Overall, these results suggest that, in the sampled populations, Zn
      tolerance has been increased in metallicolous populations through selection on
      standing genetic variation within local nonmetallicolous ancestral populations.

PMID- 19863733
TI  - Alveolar recruitment strategy and PEEP improve oxygenation, dynamic compliance of
      respiratory system and end-expiratory lung volume in pediatric patients
      undergoing cardiac surgery for congenital heart disease.
AB  - OBJECTIVE: Optimizing alveolar recruitment by alveolar recruitment strategy (ARS)
      and maintaining lung volume with adequate positive end-expiratory pressure (PEEP)
      allow preventing ventilator-induced lung injury (VILI). Knowing that PEEP has its
      most beneficial effects when dynamic compliance of respiratory system (Crs) is
      maximized, we hypothesize that the use of 8 cm H(2)O PEEP with ARS results in an
      increase in Crs and end-expiratory lung volume (EELV) compared to 8 cm H(2)O PEEP
      without ARS and to zero PEEP in pediatric patients undergoing cardiac surgery for
      congenital heart disease. METHODS: Twenty consecutive children were studied.
      Three different ventilation strategies were applied to each patient in the
      following order: 0 cm H(2)O PEEP, 8 cm H(2)O PEEP without an ARS, and 8 cm H(2)O
      PEEP with a standardized ARS. At the end of each ventilation strategy, Crs, EELV,
      and arterial blood gases were measured. RESULTS: EELV, Crs, and P(a)O(2)/FiO(2)
      ratio changed significantly (P < 0.001) with the application of 8 cm H2O + ARS.
      Mean P(a)CO(2)- PETCO(2) difference between 0 PEEP and 8 cm H2O PEEP + ARS was
      also significant (P < 0.05). CONCLUSION: An alveolar recruitment strategy with
      relative high PEEP significantly improves Crs, oxygenation, P(a)CO(2)- PETCO(2)
      difference, and EELV in pediatric patients undergoing cardiac surgery for
      congenital heart disease.

PMID- 19863734
TI  - Ultrasound guided internal jugular vein access in children and infant: a meta
      analysis of published studies.
AB  - INTRODUCTION: Central venous catheter placement is technically difficult in
      pediatric population especially in the younger patients. Ultrasound prelocation
      and/or guidance (UPG) of internal jugular vein (IJV) access has been shown to
      decrease failure rate and complications related to this invasive procedure. The
      goal of the present study was to perform a systematic review of the advantages of
      UPG over anatomical landmarks (AL) during IJV access in children and infants.
      MATERIAL AND METHODS: A comprehensive literature search was conducted to identify
      clinical trials that focused on the comparison of UPG to AL techniques during IJV
      access in children and infants. Two reviewers independently assessed each study
      to meet inclusion criteria and extracted data. Data from each trial were combined
      to calculate the pooled odds ratio (OR) or the mean differences (MD), and their
      95% confidence intervals [CI 95%]. I(2) statistics were used to assess statistics
      heterogeneity and to guide the use of fixed or random effect for computation of
      overall effects. Subgroup analysis was used to clarify the effects of the
      techniques used (prelocation or guidance) or the experience of practitioners.
      RESULTS: Literature found five articles. Most of the patients were cardiac
      surgery patients. In comparison with AL, UPG had no effect on IJV access failure
      rate (OR = 0.28 [0.05, 1.47], I(2) = 75%, P = 0.003), the rate of carotid artery
      puncture (OR = 0.32 [0.06, 1.62], I(2) = 68%, P = 0.01), haematoma, haemothorax,
      or pneumothorax occurrence (OR = 0.40 [0.14, 1.13], I(2) = 17%, P = 0.30, OR =
      0.72, OR = 0.81 [0.18, 3.73], I(2) = 0%, P = 0.94, respectively) and time to IJV
      access and haemothorax/pneumothorax occurrence. Subgroup analysis found an
      efficacy of ultrasound when used by novice operators or during intraoperative
      use. DISCUSSION: This current meta-analysis does not found the utility of
      ultrasound during IJV access in children and infants in increasing the success
      rate and in decreasing complications.

PMID- 19863735
TI  - Sevoflurane modulation of Ca2+ regulation in skeletal muscle sarcoplasmic
      reticulum vesicles from young and mature rabbits.
AB  - INTRODUCTION: Developmental differences in splice variants of the two key
      sarcoplasmic reticulum (SR) calcium regulatory proteins, ryanodine (RyR1), and
      sarcoendoplasmic reticulum calcium pump (SERCA1) have been linked to various
      neuromuscular disorders, but not malignant hyperthermia (MH). However, it is
      unclear whether an age-related difference in volatile anesthetic-mediated SR
      calcium function exists that could add to our current understanding of the
      clinical presentation of MH syndrome and provide insight into molecular
      mechanisms for general anesthesia that may have other physiologic and/or
      pathophysiologic significance. Therefore, the effects of sevoflurane on
      intracellular calcium regulation in isolated SR membrane vesicles from the
      skeletal muscle of healthy young rabbits were compared to their adult counterpart
      using an established in vitro model with the assumption that exposure to
      sevoflurane would elicit a weaker response in the young SR. METHODS: Through dual
      wavelength spectroscopy of Ca(2+): Arsenazo III difference absorbance, the
      effects of sevoflurane on SR Ca(2+) uptake rate and release in heavy and light
      fraction SR membrane vesicles isolated from the white muscle of anesthetized,
      postweaned (age = 6 weeks, n = 5) and adult (age = 6 months, n = 5) male New
      Zealand rabbits were examined. RESULTS: The adult group showed a 50% increase in
      Ca(2+) uptake rate from control at both subclinical and clinically relevant
      anesthetic concentrations, whereas in the SR from the younger animals, Ca(2+)
      uptake rate was not altered by any concentration of sevoflurane. The sensitivity
      of both the low and high affinity Ca(2+)-binding sites on RyR1 was increased by
      sevoflurane to the same extent in the SR vesicles from the young and mature adult
      rabbits. Interestingly, a greater potency of sevoflurane for the high affinity
      binding site was identified, and this was independent of age. CONCLUSIONS: These
      findings suggest that the sensitivity of the SR to sevoflurane-mediated Ca(2+)
      uptake may be increased with maturity, while an analogous developmental effect on
      RyR1 is less probable. Nonetheless, this study shows for the first time that a
      potent inhalational agent such as sevoflurane can influence the high affinity SR
      calcium-binding site by lowering the extraluminal concentration of calcium
      necessary to trigger calcium release. While this may not be of consequence when
      inhaled anesthetics are administered to normal children or adults, it may have
      life-threatening consequences in carriers of RyR1 mutations.

PMID- 19863736
TI  - Comparison of the intubation with the Storz video laryngoscope and standard
      direct laryngoscopy in pediatric patients.

PMID- 19863737
TI  - Reversal of rocuronium-induced profound neuromuscular block by sugammadex in
      Duchenne muscular dystrophy.
AB  - A case is reported in which a child with Duchenne muscular dystrophy received a
      dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block.
      Sugammadex is the first selective relaxant binding agent and reverses rocuronium-
      and vecuronium-induced neuromuscular block. A fast and efficient recovery from
      profound neuromuscular block was achieved, and no adverse events or other safety
      concerns were observed.

PMID- 19863738
TI  - Potential hazard of endotracheal tube ISO connector.

PMID- 19863739
TI  - Reduced-dose rocuronium for day-case tonsillectomy in children where volatile
      anaesthetics are not used: operating room time saving.
AB  - OBJECTIVES: Mivacurium, rocuronium, and vecuronium are neuromuscular blocking
      agents (NMB) commonly used in pediatric day-case anesthesia. Mivacurium is the
      most appropriate NMB for short surgical procedures where NMB drugs were required
      but is not available in all countries. AIM: We evaluated the operating room time
      minimization after reduced-dose rocuronium (0.45 mg x kg(-1)) during elective day
      case tonsillectomy in children. METHODS/MATERIALS: One hundred and five children
      (6-9 years, ASA I/II status) scheduled for day-case tonsillectomy were included
      in prospective, double blind clinical study. Children were randomly divided in
      three equal groups. All children were premedicated (midazolam 0.25 mg x kg(-1)
      orally, EMLA). Anesthesia was induced (2.5 mg x kg(-1)) and maintained (0.1 mg x
      kg(-1) x min(-2)) by propofol and alfentanil (0.0015 mg x kg(-1) x min(-1)) and
      supplemented by inhalation mixture of 50% of O2/Air. Neuromuscular block was
      achieved by vecuronium (0.1 mg x kg(-1)) (V) or rocuronium in standard (0.6
      mg.kg(-1)) (R) or reduced dose (0.45 mg x kg(-1)) (LD). Neuromuscular
      transmission was monitored by acceleromyography. Time analysis of NMB drugs
      action was performed. RESULTS: Time difference from the end of tonsillectomy to
      T90 neuromuscular block recovery was significantly shorter in LD Group (7.3 +/-
      0.41 min), (V = 15.9 +/- 1.06, R = 16.0 +/- 1.7 min) (P = 0.0011). The onset time
      of neuromuscular block was prolonged in LD Group (LD=3.1 +/- 0.4, R = 1.3 +/-
      0.4, V = 2.2 +/- 0.2 min) (P = 0.0039) without changing the intubating
      conditions. The maximum operation room time saving per each tonsillectomy was 37%
      in LD Group (Group V 21%, Group R 17%) (P = 0.0001). Low incidence of
      postoperative nausea and vomiting (PONV) 3-6% (0.4577) and good visual analog
      scale (VAS) score (< or =2) (0.5969) were found in all study groups 12 h after
      surgery. CONCLUSIONS: Reduced-dose rocuronium in addition with propofol and
      alfentanil in children where volatile anesthetics are not used effectively saves
      the operating room time during short elective surgical procedures, avoids delays
      in patient recovery, allows high level of acceptable intubating conditions, and
      improves the optimal surgical work. Low incidences of PONV as VAS score may
      achieved successfully.

PMID- 19863740
TI  - An acute pain service improves postoperative pain management for children
      undergoing selective dorsal rhizotomy.
AB  - BACKGROUND: A continuous epidural infusion of morphine is the pain treatment
      modality for children undergoing selective dorsal rhizotomy (SDR) in our
      institution. The aim of the study was to evaluate the impact of having an
      organized acute pain service (APS) on postoperative pain management of these
      children. METHODS: We conducted a retrospective cohort study using anesthetic
      records and the APS database to compare the postoperative pain management of
      children undergoing SDR before and after the introduction of the APS at the
      Montreal Children's Hospital in April 2001. Ninety-two consecutive children who
      had their surgery between January 1997 and July 2006 were included. We collected
      data regarding postoperative pain, opioid-induced side effects, complications
      (sedation, desaturations < 92%), and hospital length of stay. RESULTS: Pain
      scores were documented more frequently after the implementation of the APS (61%
      vs 48.5%). Sedation scores were documented only after the implementation of the
      APS. Postoperative desaturation was significantly more frequent in the pre-APS
      group compared to the APS group (45.5% vs 6.8%, P < 0.001). Despite the fact that
      the epidural catheter was in place for the same duration for both groups [median
      of 3 days (3-3 25-75%ile)], the duration of hospitalization was 1 day shorter in
      the APS group compared to the pre-APS group [median of 5 (5-5 25-75%ile) vs 6 (5
      6 25-75%ile) days, P < 0.001]. CONCLUSIONS: Although we recognize that it is
      possible that there were changes in care not related specifically to the
      introduction of a dedicated APS that occurred in our institution that resulted in
      improvements in general postoperative care and in length of stay, our study did
      show that having an organized APS allowed to significantly decrease the incidence
      of postoperative oxygen desaturation and to decrease the hospital length of stay
      by 1 day.

PMID- 19863741
TI  - School-aged children's experiences of postoperative music medicine on pain,
      distress, and anxiety.
AB  - AIM: To test whether postoperative music listening reduces morphine consumption
      and influence pain, distress, and anxiety after day surgery and to describe the
      experience of postoperative music listening in school-aged children who had
      undergone day surgery. BACKGROUND: Music medicine has been proposed to reduce
      distress, anxiety, and pain. There has been no other study that evaluates effects
      of music medicine (MusiCure) in children after minor surgery. METHODS: Numbers of
      participants who required analgesics, individual doses, objective pain scores
      (Face, Legs, Activity, Cry, Consolability [FLACC]), vital signs, and
      administration of anti-emetics were documented during postoperative recovery
      stay. Self-reported pain (Coloured Analogue Scale [CAS]), distress (Facial
      Affective Scale [FAS]), and anxiety (short State-Trait Anxiety Inventory [STAI])
      were recorded before and after surgery. In conjunction with the completed
      intervention semi-structured qualitative interviews were conducted. RESULTS: Data
      were recorded from 80 children aged 7-16. Forty participants were randomized to
      music medicine and another 40 participants to a control group. We found evidence
      that children in the music group received less morphine in the postoperative care
      unit, 1/40 compared to 9/40 in the control group. Children's individual FAS
      scores were reduced but no other significant differences between the two groups
      concerning FAS, CAS, FLACC, short STAI, and vital signs were shown. Children
      experienced the music as 'calming and relaxing.' CONCLUSIONS: Music medicine
      reduced the requirement of morphine and decreased the distress after minor
      surgery but did not else influence the postoperative care.

PMID- 19863742
TI  - The role of catastrophizing in the prediction of postoperative pain.
AB  - OBJECTIVE: Catastrophizing has been broadly conceived as an exaggerated negative
      "mental set" brought to bear during actual or anticipated pain experience and has
      risen to the status of one of the most important psychological predictors of
      pain. The present study aimed at investigating the relationship between
      catastrophizing and postoperative pain outcomes (pain intensity and analgesia
      use) in patients undergoing elective instrumented lumbar fusion surgery. DESIGN:
      On the day before surgery, 61 patients completed the Greek versions of the Pain
      Catastrophizing Scale and the Hospital Anxiety and Depression Scale. On
      postoperative days 1 and 2, pain intensity (at rest and during activity) on the
      Verbal Rating Scale as well as intravenous patient-controlled analgesia fentanyl
      use were assessed. RESULTS: Catastrophizing and gender predicted postoperative
      pain intensity at rest, whereas catastrophizing emerged as the unique predictor
      of postoperative pain intensity during activity. Catastrophizing and anxiety
      predicted analgesic use. CONCLUSIONS: The present study findings suggest that it
      is possible to preoperatively identify patients at risk for experiencing more
      severe pain in the postoperative recovery period. In such cases, consideration
      might be given to utilizing a variety of resources to ameliorate or prevent pain.

PMID- 19863743
TI  - SUNCT syndrome successfully treated with the combination of oxcarbazepine and
      gabapentin.
AB  - Short-lasting unilateral neuralgiform headache attacks with conjunctival
      injection and tearing (SUNCT) is a syndrome of intermittent, brief, unilateral,
      severe paroxysms of orbital-temporal pain recurring multiple times per day. The
      pain modulation is often very difficult. The reported SUNCT patient is the first
      who responded to a combination treatment of oxcarbazepine and gabapentin.

PMID- 19863744
TI  - Paraplegia following image-guided transforaminal lumbar spine epidural steroid
      injection: two case reports.
AB  - OBJECTIVE: To present two case reports of a rare but devastating injury after
      image-guided, lumbar transforaminal injection of steroids, and to explore
      features in common with previously reported cases. BACKGROUND: Image
      (fluoroscopic and computed tomography [CT])-guided, lumbar transforaminal
      injections of corticosteroids have been adopted as a treatment for radicular
      pain. Complications associated with these procedures are rare, but can be severe.
      CASE REPORTS: An 83-year-old woman underwent a fluoroscopically guided, left L3
      L4, transforaminal injection of betamethasone (Celestone Soluspan). A 79-year-old
      man underwent a CT-guided, right L3-L4, transforaminal injection of
      methylprednisolone (DepoMedrol). Both patients developed bilateral lower
      extremity paralysis, with neurogenic bowel and bladder, immediately after the
      procedures. Magnetic resonance imaging scans were consistent with spinal cord
      infarction. There was no evidence of intraspinal mass or hematoma. CONCLUSION:
      These cases consolidate a pattern emerging in the literature. Distal cord and
      conus injury can occur following transforaminal injections at lumbar levels,
      whether injection is on the left or right. This conforms with the probability of
      radicular-medullary arteries forming an arteria radicularis magna at lumbar
      levels. All cases used particulate corticosteroids, which promotes embolization
      in a radicular artery as the likely mechanism of injury. The risk of this
      complication can be reduced, and potentially eliminated, by the utilization of
      particulate free steroids, testing for intra-arterial injection with digital
      subtraction angiography, and a preliminary injection of local anesthetic.

PMID- 19863745
TI  - Postdural puncture headache in complex regional pain syndrome: a retrospective
      observational study.
AB  - OBJECTIVE: To describe the unusual course of postdural puncture headache (PDPH)
      after pump implantation for intrathecal baclofen (ITB) administration in patients
      with complex regional pain syndrome (CRPS)-related dystonia. DESIGN: Case series
      based on data collected from 1996 to 2005. Setting. Movement disorders clinic,
      university hospital. PATIENTS: A total of 54 patients with CRPS-related dystonia
      who were treated with ITB. RESULTS: A high incidence (76%) and prolonged course
      (median 18 days, range 2 days to 36 months) of PDPH was found. Radionuclide
      studies performed in two patients with long-lasting symptoms (12-16 months) did
      not reveal cerebrospinal fluid (CSF) leakage. In patients without signs of CSF
      leakage (N = 38), epidural blood patches administered in 24 patients were
      effective in 54%, while ketamine infusions administered in six patients were
      effective in 67%. CONCLUSIONS: Our observations may suggest that other mechanisms
      besides intracranial hypotension play a role in the initiation and maintenance of
      PDPH in CRPS and stimulate new directions of research on this topic.

PMID- 19863746
TI  - Occipital nerve stimulator lead pathway length changes with volunteer movement:
      an in vitro study.
AB  - BACKGROUND: Occipital nerve stimulation is a modality reserved for refractory
      headache disorders. Leads (wires) are inserted subcutaneously in the occipital
      region to stimulate the distal C1-3 nerves; lead migration may result from
      repeated mechanical forces on the lead associated with patient movement. The
      primary aim of this study was to determine implantation pathways associated with
      the least pathway length change secondary to body movement in an in vitro model
      of an occipital stimulator system. METHODS: After institutional review board
      approval, 10 volunteers were recruited. The expected pathway of an occipital
      stimulator system was identified and measured externally, and then changes in
      pathway length were measured during various volunteer movements, including neck
      and low back flexion, extension, rotation, and lateral flexion. The pathways
      studied included those that connect internal pulse generators in the gluteal, low
      abdominal, and infraclavicular regions to occipital leads inserted via a cervical
      or retromastoid approach. RESULTS: The flexion/extension pathway length changes
      associated with midline occipital and retromastoid sites to the infraclavicular
      site were significantly less than those pathways to the periscapular site. Also,
      the abdominal site was associated with less pathway length change during
      flexion/extension than the gluteal site. CONCLUSIONS: Internal pulse generators
      in sites other than the buttock, including infraclavicular or low abdomen, may be
      associated with lower lead migration risk. There are many considerations when
      selecting insertion sites and lead pathways for occipital nerve stimulation.
      Implanters and patients may consider these results when contemplating surgical
      approaches to this challenging form of peripheral nerve stimulation.

PMID- 19863747
TI  - Pelvic girdle pain and low back pain in pregnancy: a review.
AB  - Pregnancy-related pelvic girdle pain (PGP) and pregnancy-related low back pain
      (PLBP) are common problems with significant physical, psychological, and
      socioeconomic implications. There are several management options that are
      underutilized because of lack of comprehensive knowledge by health-care
      professionals and fear of harmful effects of treatment on the developing fetus.
      Interventions such as patient education, the use of pelvic belts, acupuncture,
      and aquatic and tailored postpartum exercises can be of some benefit to these
      patients. This article will focus on the diagnosis and management of PGP and
      PLBP, with discussion of terminology, epidemiology, risk factors,
      pathophysiology, and prognosis.

PMID- 19863748
TI  - A severe case of complex regional pain syndrome I (reflex sympathetic dystrophy)
      managed with spinal cord stimulation.
AB  - Complex regional pain syndrome is a condition that usually affects the upper or
      lower extremities. The cause is not clearly understood. We report a case of a
      severe form of a rapidly progressive complex regional pain syndrome type I
      developing after a right shoulder injury managed with spinal cord stimulation
      (SCS). After failed conservative treatments, a rechargeable SCS system was
      implanted in the cervical spine. Allodynia and dystonia improved but the patient
      subsequently developed similar symptoms in lower right extremity followed by her
      lower left extremity. The patient became wheelchair bound. A second rechargeable
      SCS with a paddle electrode was implanted for the lower extremity coverage. The
      patient's allodynia and skin lesions improved significantly. However, over time,
      her initial symptoms reappeared which included skin breakdown. Due to the need
      for frequent recharging, the system was removed. During explantation of the
      surgical paddle lead, it was noted by the neurosurgeon that the contacts of the
      paddle lead were detached from the lead. After successful implantation of another
      SCS system, the patient was able to reduce her medications and is now able to
      ambulate with the use of a left elbow crutch.

PMID- 19863749
TI  - The role of OROS hydromorphone in the management of cancer pain.
AB  - The vast majority of cancer patients experience pain, and treatment with opioids
      offers the most effective option for pain management. Long-lasting opioid
      formulations are usually used as cancer pain management strategies. This review
      surveys the available literature on the only available once-daily sustained
      release formulation of hydromorphone, and its use in cancer pain management.
      Sustained-release (SR) formulations have a more consistent opioid plasma
      concentration, thereby minimizing the peaks and troughs associated with immediate
      release opioid formulations. OROS hydromorphone (Jurnista, Janssen
      Pharmaceuticals, NV, Beerse, Belgium) releases hydromorphone over a 24-hour
      dosing period. Studies comparing its efficacy with other opioids such as morphine
      and oxycodone found comparable results overall. Recent trials have provided
      evidence of decreased rescue medication use for breakthrough pain, a good safety
      profile, and quality of life benefits. It appears to be an efficacious and well
      tolerated treatment. The pharmacokinetics of OROS hydromorphone are linear and
      dose-proportional, and only minimally affected by the presence or absence of
      food. In addition, the SR properties of OROS hydromorphone are maintained in the
      presence of alcohol, with no dose dumping of hydromorphone. This formulation
      shows promise as an addition to cancer pain management strategies, although
      further randomized, double-blind trials are needed to confirm this.

PMID- 19863750
TI  - The influence of physical activity on ghrelin and IGF-1/IGFBP-3 levels in
      children and adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVES: The aim of the study was to determine the influence of regular
      physical activity on ghrelin and IGF-1/IGFBP-3 levels during a diabetes camp.
      METHODS: Twenty-eight children and adolescents (14 boys; mean age 12.1 yr) with
      type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2
      wk diabetes camp that features increased regular physical activities have been
      studied. Serum levels of ghrelin (total and acylated), growth hormone (GH),
      insulin-like growth factor-1 (IGF-1), insulin-like growth factor-bindng protein-3
      (IGFBP-3) and insulin were measured in fasting state on day 1 and day 14.
      Improvement of metabolic control was documented by haemoglobin A1c (HbA1c).
      Glucose levels and insulin doses were determined daily. RESULTS: Mean insulin
      dosage decreased from 0.87 to 0.78 U/kg/d, mean HbA1c levels decreased from 8.6
      to 8.3%, but the changes were not statistical. There was a significant decline in
      total ghrelin. IGFBP-3 and IGF-1 decreased also significantly. Total basal
      ghrelin was inversely related to the change in IGFBP-3. CONCLUSIONS: We
      hypothesize an association between ghrelin and metabolic control in T1DM. Higher
      ghrelin levels might be associated with poor metabolic control. The dynamic of
      IGFBP-3 levels appears to be under the influence of basal ghrelin concentrations
      in T1DM.

PMID- 19863751
TI  - Symptomatic omphalomesenteric duct remnants in children.
AB  - BACKGROUND: The present study gathers a single institutional experience of
      symptomatic omphalomesenteric duct (OMD) remnants in children with an emphasis on
      the age and modes of presentation, the surgical intervention and the
      histopathological findings. METHODS: The data on children who underwent surgical
      treatment for symptomatic OMD remnants during a 17-year period were reviewed
      retrospectively, excluding incidental diverticulectomies. RESULTS: A total of 59
      children with a median age of 36 months underwent operations for symptomatic OMD
      remnants. There were 48 boys and 11 girls. The presenting signs were
      gastrointestinal tract (GIT) obstruction in 21 (36%) patients, acute abdomen in
      18 (31%), umbilical abnormalities in 17 (29%), and rectal bleeding in three (5%).
      Patients presenting with umbilical anomalies were significantly younger than
      others. At surgery, a wedge resection of the remnant was carried out in 32 cases
      and an ileal resection was carried out in 27. Children presenting with GIT
      obstruction underwent segmentary ileal resection more often than other groups.
      Histopathology revealed inflammation in 26 (44%) specimens, ectopic tissue in 18
      (31%) and necrosis in four (7%). Ectopic gastric mucosa was detected in 15
      specimens, pancreatic tissue in two and both gastric and pancreatic tissue in
      one. CONCLUSIONS: Symptomatic OMD remnants in children most commonly presented
      with GIT obstruction, acute abdomen and umbilical anomalies. Rectal bleeding was
      not a predominant finding in the present series. Surgery is curative and can
      safely be done either by way of wedge resection or ileal segmentary resection.
      Ectopic tissue is detected in approximately one third of symptomatic remnants.

PMID- 19863752
TI  - Birth outcomes and risk factors in adolescent pregnancies: results of a Taiwanese
      national survey.
AB  - BACKGROUND: This study explores birth outcomes and determinants in adolescent
      pregnancies, using subjects drawn from the Taiwan Birth Cohort Study (TBCS) from
      2005. METHODS: Through completed interviews and surveys with mothers or other
      family members, differences in birth outcomes and personal, pregnancy and social
      profiles of mothers were analyzed. RESULTS: A total of 533 adolescent mothers
      (<20 years old) and 9347 adult mothers (20-34 years old) were included in our
      study. There was a significantly higher incidence of low birthweight (LBW) (<2500
      g, 10.2% vs 5.6%) and premature birth (<37 weeks, 14.8% vs 8.6%) in the
      adolescent group. When adjusted for covariates in the multiple-variable model,
      youth remained a risk factor for LBW (OR = 1.50, 95%CI 1.09, 2.07) and premature
      delivery (OR = 1.42, 95%CI 1.07, 1.89). Age, prenatal care and weight gain during
      pregnancy are important predictors of LBW and premature birth. CONCLUSION:
      Adolescent pregnancy carries a high-risk of LBW and premature birth. Inadequate
      prenatal care and weight gain during pregnancy are contributing factors that
      could be improved through strategies of health education, family support and case
      management.

PMID- 19863753
TI  - Game-based peripheral biofeedback for stress assessment in children.
AB  - BACKGROUND: Peripheral biofeedback is considered to be an efficient method for
      assessment and stress mitigation in children. The aim of the present study was to
      assess the levels of stress and stress mitigation in healthy school children
      (HSC), in children with cystic fibrosis (CF), general anxiety (GA) and attention
      deficit-hyperactivity disorder (ADHD). METHODS: Each investigated group (HSC, CF,
      GA, ADHD) consisted of 30 school-aged children from both sexes. Psychological
      characteristics were evaluated on Eysenck Personality Questionnaire (EPQ). The
      lie scale was used to determine participant honesty. Four biofeedback games using
      a pulls detector were applied for assessment of the stress levels as well as to
      evaluate ability to relax. RESULTS: EPQ found more psychopathological traits (P <
      0.001) and less extroversion (P < 0.001) in children with GA and ADHD. In
      addition, high neurotic tendencies were found in children with CF (P < 0.01) and
      GA (P < 0.01). Unexpectedly, the lie scale was lower in ADHD children (P < 0.01)
      than in all other groups (HSC, CF, GA). The Magic blocks score was significantly
      different in relaxation levels between control and CF children (P < 0.05). Speed
      in the game Canal was significantly different in relaxation levels between
      healthy controls and all other groups, but no changes in pulls, as a relaxation
      measure, were found during the game. The CF group had much more commissions
      stemming from impulsivity (t= 5.71, P < 0.01), while the GA and ADHD children had
      more inattention omissions (P < 0.05). Strong negative correlation between age
      and pulls (r= 0.49, P= 0.003) and strong negative correlation between age and
      omissions (r=-0.86, P= 0.029) were found among all groups analyzed. CONCLUSIONS:
      The ability to learn stress mediation is correlated with age. All three groups of
      children had significantly lower relaxation levels when compared to healthy
      controls. Relaxation was more difficult for children with GA or ADHD, and easier
      for children with CF.

PMID- 19863754
TI  - Different enhancement of senescence induced by metabolic products of Alternaria
      alternata in tobacco leaves of different ages.
AB  - The purpose of this study was to explore the mechanisms by which Alternaria
      alternata damages tobacco (Nicotiana tabacum) leaves. Treatment with A. alternata
      metabolic products enhanced senescence in leaves of different ages, as indicated
      by the significant decrease in chlorophyll, soluble protein, photosynthetic O(2)
      evolution and catalase (CAT, EC 1.11.1.6) activity as well as an increase in
      H(2)O(2) content. The induction of senescence by A. alternata metabolic products
      increased as the age of the leaves increased. A. alternata metabolic products
      greatly influenced the behavior of photosystem II (PSII) in the leaves: oxygen
      evolving complex (OEC) activity and electron transport from primary quinone
      electron acceptor of PS II (Q(A)) to secondary quinone electron acceptor of PS II
      (Q(B)) were both significantly inhibited. This inhibition also became more
      pronounced in older leaves. In vitro experiments revealed that, without the
      influence of natural senescence, the A. alternata metabolic products directly
      inhibited the activity of a commercial CAT solution and inhibited photosynthetic
      O(2) evolution, which resulted in excess PSII excitation pressure and an
      overaccumulation of H(2)O(2) in leaf segments. These results suggest that the
      significant declines in photosynthesis and CAT activity induced by the metabolic
      products of A. alternata were important contributors to the overaccumulation of
      reactive oxygen species (ROS), which accelerated senescence in tobacco leaves.
      The fact that the enhancement of senescence was getting more pronounced with the
      age of tobacco leaves might be related to the fact that older leaves already had
      higher H(2)O(2) levels and less antioxidant activity as reflected in lower CAT
      activity.

PMID- 19863755
TI  - The gymnosperm Pinus pinea contains both AOX gene subfamilies, AOX1 and AOX2.
AB  - The gymnosperm Pinus pinea L. (stone pine) is a typical Mediterranean pine used
      for nuts and timber production, and as an ornamental around the world. Pine
      genomes are large in comparison to other species. The hypothesis that
      retrotransposons, such as gymny, made a large contribution to this alteration in
      genome size was recently confirmed. However, P. pinea is unique in other various
      aspects. P. pinea demonstrates a different pattern of gymny organization than
      other Pinus subgenera. Additionally, P. pinea has a highly recalcitrant behaviour
      in relation to standard conifer protocols for the induction of somatic
      embryogenesis or rooting. Because such types of cell reprogramming can be
      explained as a reaction of plant cells to external stress, it is of special
      interest to study sequence peculiarities in stress-inducible genes, such as the
      alternative oxidase (AOX). This is the first report containing molecular evidence
      for the existence of AOX in gymnosperms at the genetic level. P. pinea AOXs were
      isolated by a polymerase chain reaction (PCR) approach and three genes were
      identified. Two of the genes belong to the AOX1 subfamily and one belongs to the
      AOX2 subfamily. The existence of both AOX subfamilies in gymnosperms is reported
      here for the first time. This discovery supports the hypothesis that AOX1 and
      AOX2 subfamilies arose prior to the separation of gymnosperms and angiosperms,
      and indicates that the AOX2 is absent in monocots because of subsequent gene loss
      events. Polymorphic P. pinea AOX1 sequences from a selected genetic clone are
      presented indicating non-allelic, non-synonymous and synonymous translation
      products.

PMID- 19863756
TI  - Alternative oxidase involvement in Daucus carota somatic embryogenesis.
AB  - Plant alternative oxidase (AOX) is a mitochondrial inner membrane enzyme involved
      in alternative respiration. The critical importance of the enzyme during
      acclimation upon stress of plant cells is not fully understood and is still an
      issue of intensive research and discussion. Recently, a role of AOX was suggested
      for the ability of plant cells to change easily its fate upon stress. In order to
      get new insights about AOX involvement in cell reprogramming, quantitative real
      time polymerase chain reaction (PCR) and inhibitor studies were performed during
      cell redifferentiation and developmental stages of Daucus carota L. somatic
      embryogenesis. Transcript level analysis shows that D. carota AOX genes (DcAOX1a
      and DcAOX2a) are differentially expressed during somatic embryogenesis. DcAOX1a
      shows lower expression levels, being mainly down-regulated, whereas DcAOX2a
      presented a large up-regulation during initiation of the realization phase of
      somatic embryogenesis. However, when globular embryos start to develop, both
      genes are down-regulated, being this state transient for DcAOX2a. In addition,
      parallel studies were performed using salicylhydroxamic acid (SHAM) in order to
      inhibit AOX activity during the realization phase of somatic embryogenesis.
      Embryogenic cells growing in the presence of the inhibitor were unable to develop
      embryogenic structures and its growth rate was diminished. This effect was
      reversible and concentration dependent. The results obtained contribute to the
      hypothesis that AOX activity supports metabolic reorganization as an essential
      part of cell reprogramming and, thus, enables restructuring and de novo cell
      differentiation.

PMID- 19863757
TI  - Moesin/ezrin: a specific role in cell metastasis?

PMID- 19863759
TI  - Routine use of weaning predictors: not so fast.
AB  - Weaning from mechanical ventilation remains a major challenge for critical care
      physicians. Because subjective criteria are inaccurate, objective measurements
      consisting of clinical criteria and physiologic tests (weaning predictors) have
      been used to facilitate decision-making. An integrated weaning index calculated
      as the product of static compliance and arterial oxygen saturation divided by the
      frequency-tidal volume ratio appears to be more accurate than other currently
      available predictors. Despite the accuracy of this new test, a beneficial effect
      on outcome is yet to be proven.

PMID- 19863758
TI  - Time course of attentional bias in anxiety: emotion and gender specificity.
AB  - Anxiety is characterized by cognitive biases, including attentional bias to
      emotional (especially threatening) stimuli. Accounts differ on the time course of
      attention to threat, but the literature generally confounds emotional valence and
      arousal and overlooks gender effects, both addressed in the present study.
      Nonpatients high in self-reported anxious apprehension, anxious arousal, or
      neither completed an emotion-word Stroop task during event-related potential
      (ERP) recording. Hypotheses differentiated time course of preferential attention
      to emotional stimuli. Individuals high in anxious apprehension and anxious
      arousal showed distinct early ERP evidence of preferential processing of
      emotionally arousing stimuli along with some evidence for gender differences in
      processing. Healthy controls showed gender differences at both early and later
      processing stages. The conjunction of valence, arousal, and gender is critical in
      the time course of attentional bias.

PMID- 19863761
TI  - Coming soon to an ICU near you: severe pandemic influenza in ICU patients in
      Spain.
AB  - A novel strain of swine influenza A H1N1 has already disseminated worldwide and
      has become a major clinical problem for intensive care units in selected areas.
      Many regions in the southern hemisphere are currently struggling to keep up with
      the influx of severely affected patients with acute respiratory failure from
      primary influenza pneumonia. The northern hemisphere is bracing for a similar
      surge of patients over this winter's influenza season. This initial report of
      ventilatory needs for patients with severe influenza pneumonia in Spanish
      intensive care units provides a useful guide of what to expect and how to respond
      to the challenge of pandemic influenza.

PMID- 19863760
TI  - Bench-to-bedside review: Beta-adrenergic modulation in sepsis.
AB  - Sepsis, despite recent therapeutic progress, still carries unacceptably high
      mortality rates. The adrenergic system, a key modulator of organ function and
      cardiovascular homeostasis, could be an interesting new therapeutic target for
      septic shock. Beta-adrenergic regulation of the immune function in sepsis is
      complex and is time dependent. However, beta2 activation as well as beta1
      blockade seems to downregulate proinflammatory response by modulating the
      cytokine production profile. beta1 blockade improves cardiovascular homeostasis
      in septic animals, by lowering myocardial oxygen consumption without altering
      organ perfusion, and perhaps by restoring normal cardiovascular variability. Beta
      blockers could also be of interest in the systemic catabolic response to sepsis,
      as they oppose epinephrine which is known to promote hyperglycemia, lipid and
      protein catabolism. The role of beta-blockers in coagulation is less clear cut.
      They could have a favorable role in the septic pro-coagulant state, as beta1
      blockade may reduce platelet aggregation and normalize the depressed fibrinolytic
      status induced by adrenergic stimulation. Therefore, beta1 blockade as well as
      beta2 activation improves sepsis-induced immune, cardiovascular and coagulation
      dysfunctions. Beta2 blocking, however, seems beneficial in the metabolic field.
      Enough evidence has been accumulated in the literature to propose beta-adrenergic
      modulation, beta1 blockade and beta2 activation in particular, as new promising
      therapeutic targets for septic dyshomeostasis, modulating favorably immune,
      cardiovascular, metabolic and coagulation systems.

PMID- 19863762
TI  - Targeting TNF-alpha for cancer therapy.
AB  - As the tumor vasculature is a key element of the tumor stroma, angiogenesis is
      the target of many cancer therapies. Recent work published in BMC Cell Biology
      describes a fusion protein that combines a peptide previously shown to home in on
      the gastric cancer vasculature with the anti-tumor cytokine TNF-alpha, and
      assesses its potential for gastric cancer therapy.

PMID- 19863763
TI  - TEs or not TEs? That is the evolutionary question.
AB  - Transposable elements (TEs) have contributed a wide range of functional sequences
      to their host genomes. A recent paper in BMC Molecular Biology discusses the
      creation of new transcripts by transposable element insertion upstream of
      retrocopies and the involvement of such insertions in tissue-specific post
      transcriptional regulation.

PMID- 19863764
TI  - Clinical review: Goal-directed therapy in high risk surgical patients.
AB  - A small group of patients account for the majority of peri-operative morbidity
      and mortality. These 'high-risk' patients have a poor outcome due to their
      inability to meet the oxygen transport demands imposed on them by the nature of
      the surgical response during the peri-operative period. It has been shown that by
      targeting specific haemodynamic and oxygen transport goals at any point during
      the peri-operative period, the outcomes of these patients can be improved. This
      goal directed therapy includes the use of fluid loading and inotropes, in order
      to optimize the preload, contractility and afterload of the heart whilst
      maintaining an adequate coronary perfusion pressure. Despite the benefits seen,
      it remains a challenge to implement this management due to difficulties in
      identifying these patients, scepticism and lack of critical care resources.

PMID- 19863765
TI  - Year in review 2008: Critical Care--respirology.
AB  - Original research contributions published in Critical Care in 2008 in the fields
      of respirology and critical care medicine are summarized. Eighteen articles were
      grouped into the following categories: acute lung injury and acute respiratory
      distress syndrome, mechanical ventilation, mechanisms of ventilator-induced lung
      injury, and tracheotomy decannulation and non-invasive ventilation.

PMID- 19863766
TI  - Year in review 2008: Critical Care--trauma.
AB  - Eleven papers on trauma published in Critical Care during 2008 addressed
      traumatic brain injury (TBI), burns, diagnostic concerns and immunosuppression.
      In regard to TBI, preliminary results indicate the utility of either magnetic
      resonance imaging (MRI) or ultrasound in measuring optic nerve sheath diameter to
      identify elevated intracranial pressure (ICP) as well as the potential benefit of
      thiopental for refractory ICP. Another investigation demonstrated that early
      extubation of TBI patients whose Glasgow Coma Scale score was 8 or less did not
      result in additional incidence of nosocomial pneumonia. Another study indicated
      that strict glucose control resulted in worse outcomes during the first week
      after TBI, but improved outcomes after the second week. Another paper showed the
      prolonged neuroprotective advantages of progesterone administration in TBI
      patients. There was also guidance on improved classifications of renal
      complications in burn patients. Another study found that patients with inhalation
      injuries and increased interleukin-6 (IL-6) and IL-10 and decreased IL-7 had
      increased mortality rates. One literature review described the disadvantages of
      prolonged immobilization or additional use of MRI for ruling out cervical spine
      injuries in obtunded TBI patients already cleared by computerized tomography
      scans. Other investigators found that higher N-terminal pro B-type natriuretic
      peptide (NT-proBNP) levels may be useful markers for post-traumatic cardiac
      impairment. Finally, an experimental model showed that both splenic apoptosis and
      lymphocytopenia may occur shortly after severe hemorrhage, thus increasing the
      threat of immunosuppression in those with severe blood loss.

PMID- 19863767
TI  - Year in review 2008: Critical Care--metabolism.
AB  - In 2008, the interest in metabolic and endocrine issues and their consequences in
      critically ill patients was high. A large proportion of the research papers
      related to these issues was related to the metabolism of glucose and its control
      and to the changes in body composition, including muscular weakness. In Critical
      Care, original reports from investigations of glucose physiology and clinical
      data from observational and interventional studies were published. Important
      reports of the effects of hormone analogues, such as vasopressin and
      hydrocortisone, and early antioxidants in selected subpopulations were also
      available in 2008.

PMID- 19863768
TI  - Year in review 2008: Critical Care--cardiology.
AB  - We review key research papers in cardiology and intensive care published during
      2008 in Critical Care. We quote studies on the same subject published in other
      journals if appropriate. Papers have been grouped into three categories: (a)
      cardiovascular biomarkers in critical illness, (b) haemodynamic management of
      septic shock, and (c) haemodynamic monitoring.

PMID- 19863769
TI  - Year in review 2008: Critical Care--nephrology.
AB  - We summarize original research in the field of critical care nephrology accepted
      or published during 2008 in Critical Care and, when considered relevant or
      directly linked to this research, in other journals. Three main topics have been
      identified for a rapid overview. (1) The classification of acute kidney injury,
      with particular attention to differences and similarities between the RIFLE and
      AKIN classifications. (2) Fluid balance in patients requiring renal replacement
      therapy (RRT) has been shown as an independent risk factor for mortality in
      critically ill patients: current evidence and uncertainties are described. (3)
      Management of anticoagulation during RRT has been explored by several researchers
      in 2008: diagnosis of heparin-induced thrombocytopenia, the use of tirofiban and
      optimal anticoagulation during drotrecogin A activated treatment have been
      evaluated.

PMID- 19863770
TI  - Moderate- to low-risk variant alleles of cutaneous malignancies and nevi: lessons
      from genome-wide association studies.
AB  - Cutaneous malignancies, especially malignant melanoma, exhibit great genetic
      heterogeneity. As a result, some individuals and families have particularly
      increased risk due to genetic predisposition to the disease. The susceptibility
      alleles range from rarely occurring, heritable, high-risk variants to
      ubiquitously occurring low-risk variants. Although until now the focus has been
      mostly towards the familial high-risk genes, the development of genome-wide
      association studies has uncovered a number of moderate- to low-risk
      predisposition alleles. The ability to specifically identify genetic variation
      associated with visible pigmentation traits and disease risk has provided a much
      richer view of the genetics of cutaneous malignancies. In this review, we provide
      an update on the recently identified risk loci. Existing clinical data, combined
      with vast genome information, will provide a better understanding of the biology
      of disease, and increased accuracy in risk prediction.

PMID- 19863771
TI  - Functional genomic and epidemiological studies reveal novel genes regulating
      cholesterol metabolism.
AB  - Elevated plasma cholesterol is a heritable trait and a risk factor for the
      development of cardiovascular disease. Although several major biochemical
      pathways regulating cholesterol metabolism have been identified, questions
      regarding the details of this regulation remain. In fact, common genetic
      polymorphisms in candidate genes explain only 5 to 7% of variation in high- and
      low-density lipoprotein cholesterol levels between individuals. This suggests
      that many of the factors influencing cholesterol metabolism, and potentially the
      etiology of cardiovascular disease, are unknown. Here, we review recent
      functional genomic research that, combined with results from genome-wide
      association studies, provides a powerful tool to identify novel candidate genes
      relevant to cholesterol metabolism.

PMID- 19863772
TI  - LINE dancing in the human genome: transposable elements and disease.
AB  - Transposable elements (TEs) have been consistently underestimated in their
      contribution to genetic instability and human disease. TEs can cause human
      disease by creating insertional mutations in genes, and also contributing to
      genetic instability through non-allelic homologous recombination and introduction
      of sequences that evolve into various cis-acting signals that alter gene
      expression. Other outcomes of TE activity, such as their potential to cause DNA
      double-strand breaks or to modulate the epigenetic state of chromosomes, are less
      fully characterized. The currently active human transposable elements are members
      of the non-LTR retroelement families, LINE-1, Alu (SINE), and SVA. The impact of
      germline insertional mutagenesis by TEs is well established, whereas the rate of
      post-insertional TE-mediated germline mutations and all forms of somatic
      mutations remain less well quantified. The number of human diseases discovered to
      be associated with non-allelic homologous recombination between TEs, and
      particularly between Alu elements, is growing at an unprecedented rate.
      Improvement in the technology for detection of such events, as well as the
      mounting interest in the research and medical communities in resolving the
      underlying causes of the human diseases with unknown etiology, explain this
      increase. Here, we focus on the most recent advances in understanding of the
      impact of the active human TEs on the stability of the human genome and its
      relevance to human disease.

PMID- 19863773
TI  - Rheumatoid arthritis: GWAS or TMI?
AB  - Genome-wide association studies are the most comprehensive and straightforward
      approach to teasing out the identity of genetic polymorphisms associated with any
      given disease or characteristic. With the availability of DNA banks from large
      cohorts of ethnically matched patients and healthy individuals it is now possible
      to define even marginal genetic associations between genetic polymorphisms and
      diseases. As increasing numbers of these studies are carried out and as
      associations with smaller and smaller risks are identified, there is the growing
      concern that the findings will be of increasingly marginal value. Thus, the glut
      of new genetic associations is rapidly overwhelming our interest in the results,
      a situation that could be described as TMI (too much information). Recent genetic
      association studies in rheumatoid arthritis suggest that we may be approaching
      the TMI stage of genome-wide association studies.

PMID- 19863774
TI  - Synthetic lethality: a framework for the development of wiser cancer
      therapeutics.
AB  - The challenge in medical oncology has always been to identify compounds that will
      kill, or at least tame, cancer cells while leaving normal cells unscathed. Most
      chemotherapeutic agents in use today were selected primarily for their ability to
      kill rapidly dividing cancer cells grown in cell culture and in mice, with their
      selectivity determined empirically during subsequent animal and human testing.
      Unfortunately, most of the drugs developed in this way have relatively low
      therapeutic indices (low toxic dose relative to the therapeutic dose). Recent
      advances in genomics are leading to a more complete picture of the range of
      mutations, both driver and passenger, present in human cancers. Synthetic
      lethality provides a conceptual framework for using this information to arrive at
      drugs that will preferentially kill cancer cells relative to normal cells. It
      also provides a possible way to tackle 'undruggable' targets. Two genes are
      synthetically lethal if mutation of either gene alone is compatible with
      viability but simultaneous mutation of both genes leads to death. If one is a
      cancer-relevant gene, the task is to discover its synthetic lethal interactors,
      because targeting these would theoretically kill cancer cells mutant in the
      cancer-relevant gene while sparing cells with a normal copy of that gene. All
      cancer drugs in use today, including conventional cytotoxic agents and newer
      'targeted' agents, target molecules that are present in both normal cells and
      cancer cells. Their therapeutic indices almost certainly relate to synthetic
      lethal interactions, even if those interactions are often poorly understood.
      Recent technical advances enable unbiased screens for synthetic lethal
      interactors to be undertaken in human cancer cells. These approaches will
      hopefully facilitate the discovery of safer, more efficacious anticancer drugs
      that exploit vulnerabilities that are unique to cancer cells by virtue of the
      mutations they have accrued during tumor progression.

PMID- 19863775
TI  - Insights into gliomagenesis: systems biology unravels key pathways.
AB  - Technological advances have enabled a better characterization of all the genetic
      alterations in tumors. A picture that emerges is that tumor cells are much more
      genetically heterogeneous than originally expected. Thus, a critical issue in
      cancer genomics is the identification of the genetic alterations that drive the
      genesis of a tumor. Recently, a systems biology approach has been used to
      characterize such alterations and find associations between them and the process
      of gliomagenesis. Here, we discuss some implications of this strategy for the
      development of new therapeutic and diagnostic protocols for cancer.

PMID- 19863776
TI  - Watching proteins in motion.
AB  - A report of the 23rd Protein Symposium 'Proteins in Motion', Boston, USA, 23-27
      July 2009.

PMID- 19863777
TI  - Why are women predisposed to autoimmune rheumatic diseases?
AB  - The majority of autoimmune diseases predominate in females. In searching for an
      explanation for this female excess, most attention has focused on hormonal
      changes--both exogenous changes (for example, oral contraceptive pill) and
      fluctuations in endogenous hormone levels particularly related to menstruation
      and pregnancy history. Other reasons include genetic differences, both direct
      (influence of genes on sex chromosomes) and indirect (such as microchimerism), as
      well as gender differences in lifestyle factors. These will all be reviewed,
      focusing on the major autoimmune connective tissue disorders: rheumatoid
      arthritis, systemic lupus erythematosus and scleroderma.

PMID- 19863778
TI  - Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR
      knock-down.
AB  - BACKGROUND: The active form of Vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), has
      strong anti-proliferative effects, yet the molecular mechanisms underneath this
      effect remain unclear. In contrast, the molecular mechanism of 1,25D for the
      regulation of calcium homeostasis has principally been resolved, demonstrating a
      pivotal role for the vitamin D receptor (VDR). RESULTS: We first addressed the
      question whether the anti-proliferative effects of 1,25D are influenced by VDR.
      Knockdown of VDR by siRNA did not affect the anti-proliferative effects of 1,25D
      in MCF7 breast cancer cells. This unanticipated finding led us to take an
      alternative approach using genome wide screens to study the molecular mechanisms
      of 1,25D in proliferation. For that purpose, four independently developed and
      stable 1,25D resistant MCF7 cell lines were analyzed. Array CGH identified a copy
      number alteration in a region of 13.5 Mb at chromosome 11q13.4-14.1 common to all
      four 1,25D resistant cell lines. Expression arrays revealed that no single gene
      was differentially expressed between the sensitive and resistant cells, but
      multiple membrane receptor signaling pathways were altered in the 1,25D resistant
      cell lines. Importantly, in the genome wide experiments neither VDR, CYP24A1 nor
      other known vitamin D signaling pathway genes were associated with 1,25D
      resistance. CONCLUSION: In conclusion, siRNA and genome wide studies both suggest
      that the anti-proliferative effects of 1,25D in MCF7 breast tumor cell lines do
      not rely on classical Vitamin D pathway per se.

PMID- 19863779
TI  - Development of lower limb range of motion from early childhood to adolescence in
      cerebral palsy: a population-based study.
AB  - BACKGROUND: The decreasing range of joint motion caused by insufficient muscle
      length is a common problem in children with cerebral palsy (CP), often worsening
      with age. In 1994 a CP register and health care programme for children with CP
      was initiated in southern Sweden. The aim of this study was to analyse the
      development of the passive range of motion (ROM) in the lower limbs during all
      the growth periods in relation to gross motor function and CP subtype in the
      total population of children with CP. METHODS: In total, 359 children with CP
      born during 1990-1999, living in the southernmost part of Sweden in the year
      during which they reached their third birthday and still living in the area in
      the year of their seventh birthday were analysed. The programme includes a
      continuous standardized follow-up with goniometric measurements of ROM in the
      lower limbs. The assessments are made by each child's local physiotherapist twice
      a year until 6 years of age, then once a year. In total, 5075 assessments from
      the CPUP database from 1994 to 1 January 2007 were analysed. RESULTS: The study
      showed a decreasing mean range of motion over the period 2-14 years of age in all
      joints or muscles measured. The development of ROM varied according to GMFCS
      level and CP subtype. CONCLUSION: We found a decreasing ROM in children with CP
      from 2-14 years of age. This information is important for both the treatment and
      follow-up planning of the individual child as well as for the planning of health
      care programmes for all children with CP.

PMID- 19863780
TI  - Common mitochondrial polymorphisms as risk factor for endometrial cancer.
AB  - Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in
      developed countries. Although the molecular genetics of this disease has been in
      the focus of many research laboratories for the last 20 years, relevant
      prognostic and diagnostic markers are still missing. At the same time
      mitochondrial DNA mutations have been reported in many types of cancer during the
      last two decades. It is therefore very likely that the mitochondrial genotype is
      one of the cancer susceptibility factors. To investigate the presence of mtDNA
      somatic mutations and distribution of inherited polymorphisms in endometrial
      adenocarcinoma patients we analyzed the D-loop sequence of cancer samples and
      their corresponding normal tissues and moreover performed mitochondrial
      haplogroup analysis. We detected 2 somatic mutation and increased incidence of
      mtDNA polymorphisms, in particular 16223C (80% patients, p = 0.005), 16126C (23%,
      p = 0.025) and 207A (19%, p = 0.027). Subsequent statistical analysis revealed
      that endometrial carcinoma population haplogroup distribution differs from the
      Polish population and that haplogroup H (with its defining polymorphism - C7028T)
      is strongly underrepresented (p = 0.003), therefore might be a cancer-protective
      factor. Our report supports the notion that mtDNA polymorphisms establish a
      specific genetic background for endometrial adenocarcinoma development and that
      mtDNA analysis may result in the development of new molecular tool for cancer
      detection.

PMID- 19863781
TI  - The scent of supercolonies: the discovery, synthesis and behavioural verification
      of ant colony recognition cues.
AB  - BACKGROUND: Ants form highly social and cooperative colonies that compete, and
      often fight, against other such colonies, both intra- and interspecifically. Some
      invasive ants take sociality to an extreme, forming geographically massive
      'supercolonies' across thousands of kilometres. The success of social insects
      generally, as well as invasive ants in particular, stems from the sophisticated
      mechanisms used to accurately and precisely distinguish colonymates from non
      colonymates. Surprisingly, however, the specific chemicals used for this
      recognition are virtually undescribed. RESULTS: Here, we report the discovery,
      chemical synthesis and behavioural testing of the colonymate recognition cues
      used by the widespread and invasive Argentine ant (Linepithema humile). By
      synthesizing pure versions of these chemicals in the laboratory and testing them
      in behavioural assays, we show that these compounds trigger aggression among
      normally amicable nestmates, but control hydrocarbons do not. Furthermore,
      behavioural testing across multiple different supercolonies reveals that the
      reaction to individual compounds varies from colony to colony -- the expected
      reaction to true colony recognition labels. Our results also show that both
      quantitative and qualitative changes to cuticular hydrocarbon profiles can
      trigger aggression among nestmates. These data point the way for the development
      of new environmentally-friendly control strategies based on the species-specific
      manipulation of aggressive behaviour. CONCLUSION: Overall, our findings reveal
      the identity of specific chemicals used for colonymate recognition by the
      invasive Argentine ants. Although the particular chemicals used by other ants may
      differ, the patterns reported here are likely to be true for ants generally. As
      almost all invasive ants display widespread unicoloniality in their introduced
      ranges, our findings are particularly relevant for our understanding of the
      biology of these damaging invaders.

PMID- 19863782
TI  - Neuroprotective effects of blockers for T-type calcium channels.
AB  - Cognitive and functional decline with age is correlated with deregulation of
      intracellular calcium, which can lead to neuronal death in the brain. Previous
      studies have found protective effects of various calcium channel blockers in
      pathological conditions. However, little has been done to explore possible
      protective effects of blockers for T-type calcium channels, which forms a family
      of FDA approved anti-epileptic drugs. In this study, we found that neurons showed
      an increase in viability after treatment with either L-type or T-type calcium
      channel antagonists. The family of low-voltage activated, or T-type calcium
      channels, comprise of three members (Cav3.1, Cav3.2, and Cav3.3) based on their
      respective main pore-forming alpha subunits: alpha1G, alpha1H, and alpha1I. Among
      these three subunits, alpha1H is highly expressed in hippocampus and certain
      cortical regions. However, T-type calcium channel blockers can protect neurons
      derived from alpha1H-/- mice, suggesting that neuroprotection demonstrated by
      these drugs is not through the alpha1H subunit. In addition, blockers for T-type
      calcium channels were not able to confer any protection to neurons in long-term
      cultures, while blockers of L-type calcium channels could protect neurons. These
      data indicate a new function of blockers for T-type calcium channels, and also
      suggest different mechanisms to regulate neuronal survival by calcium signaling
      pathways. Thus, our findings have important implications in the development of
      new treatment for age-related neurodegenerative disorders.

PMID- 19863784
TI  - Recognition of depression in children in general hospital-based paediatric units
      in Kenya: practice and policy implications.
AB  - BACKGROUND: Physical disorders are commonly comorbid with depression in children
      attending general medical facilities. However, the depression component is rarely
      recognised. METHODS: A questionnaire on sociodemographics and history of
      presenting medical conditions was administered together with the Children's
      Depression Inventory (CDI) to all 11-year-old to 17-year-old children attending
      at nine medical facilities. RESULTS: In all, 408 children were recruited from 9
      health facilities. Whereas the clinicians diagnosed a mental disorder in only
      2.5% of the sample studied, 41.3% had CDI scores that suggested mild to moderate
      depression. The highest proportion of children with depressive symptomatology was
      found at the Kenyatta National and Teaching Referral Hospital. CONCLUSION:
      Although prevalence rate for depression among children is high, detection rates
      remain low. This finding has clinical practice and policy implications within and
      outside Kenya.

PMID- 19863783
TI  - Emerging evidence of a link between the polycystins and the mTOR pathways.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease
      characterized by the formation of renal cysts. This disease can be caused by
      mutations in two genes, PKD1 and PKD2, which encode polycystin-1 (PC-1) and -2
      (PC-2), respectively.PC-1 is a large plasma membrane receptor involved in the
      regulation of several biological functions and signaling pathways, and PC-2 is a
      calcium channel of the TRP family. The two proteins associate in a complex to
      prevent cyst formation, but the precise mechanism(s) involved remain largely
      unknown.This review will focus on recent advances in our understanding of the
      functions of polycystins and their role in signal transduction.Increased activity
      of the mammalian target of rapamycin (mTOR) kinase has been observed in cysts
      found in ADPKD tissues. Rapamycin has been shown to have beneficial effects in
      rodent models of polycystic kidney disease, prompting the initiation of pilot
      clinical trials with human patients. Furthermore, a direct role for PC-1 in the
      regulation of cell growth (size) via mTOR has recently been demonstrated.Major
      advancements in the study of mTOR biology have highlighted that this kinase
      exists in association with two different complexes, mTOR complex 1 (mTORC1) and
      mTOR complex 2 (mTORC2). The mTORC1 complex regulates cell growth (size),
      proliferation, translation and autophagy, and mTORC2 regulates the actin
      cytoskeleton and apoptosis. Interestingly, mTORC2 has been shown to contain the
      kinase responsible for the phosphorylation of Akt at Serine 473. Previous studies
      have shown that PC-1 controls the PI 3-kinase/Akt cascade to regulate apoptosis
      and the actin cytoskeleton, suggesting that this receptor might regulate mTOR at
      several levels.This review aims to discuss three different, inter-related themes
      emerging from the literature: (i) studies performed in our and other laboratories
      collectively suggest that PC-1 might be able to differentially regulate the two
      mTOR complexes; (ii) several studies point to genetic and functional cross-talk
      between the PKD and TSC genes, although the molecular details remain obscure; and
      (iii) studies performed in mammals and in the unicellular algae Chlamidomonas
      Reinhardtii might highlight a link between cilia, regulation of cell size and
      regulation of the cell cycle.

PMID- 19863785
TI  - Response of Bacillus cereus ATCC 14579 to challenges with sublethal
      concentrations of enterocin AS-48.
AB  - BACKGROUND: Enterocin AS-48 is produced by Enterococcus faecalis S48 to compete
      with other bacteria in their environment. Due to its activity against various
      Gram positive and some Gram negative bacteria it has clear potential for use as a
      food preservative. Here, we studied the effect of enterocin AS-48 challenges on
      vegetative cells of Bacillus cereus ATCC 14579 by use of transcriptome analysis.
      RESULTS: Of the 5200 genes analysed, expression of 24 genes was found to change
      significantly after a 30 min treatment with a subinhibitory bacteriocin
      concentration of 0.5 microg/ml. Most of up-regulated genes encode membrane
      associated or secreted proteins with putative transmembrane segments or signal
      sequences, respectively. One operon involved in arginine metabolism was
      significantly downregulated. The BC4206-BC4207 operon was found to be the most
      upregulated target in our experiments. BC4206 codes for a PadR type
      transcriptional regulator, while BC4207 codes for a hypothetical membrane
      protein. The operon structure and genes are conserved in B. cereus and B.
      thuringiensis species, but are not present in B. anthracis and B. subtilis. Using
      real-time qPCR, we show that these genes are upregulated when we treated the
      cells with AS-48, but not upon nisin treatment. Upon overexpression of BC4207 in
      B. cereus, we observed an increased resistance against AS-48. Expression of
      BC4207 in B. subtilis 168, which lacks this operon also showed increased
      resistance against AS-48. CONCLUSION: BC4207 membrane protein is involved in the
      resistance mechanism of B. cereus cells against AS-48.

PMID- 19863786
TI  - Quantitative trait loci for resistance to trichostrongylid infection in Spanish
      Churra sheep.
AB  - BACKGROUND: For ruminants reared on grazing systems, gastrointestinal nematode
      (GIN) parasite infections represent the class of diseases with the greatest
      impact on animal health and productivity. Among the many possible strategies for
      controlling GIN infection, the enhancement of host resistance through the
      selection of resistant animals has been suggested by many authors. Because of the
      difficulty of routinely collecting phenotypic indicators of parasite resistance,
      information derived from molecular markers may be used to improve the efficiency
      of classical genetic breeding. METHODS: A total of 181 microsatellite markers
      evenly distributed along the 26 sheep autosomes were used in a genome scan
      analysis performed in a commercial population of Spanish Churra sheep to detect
      chromosomal regions associated with parasite resistance. Following a daughter
      design, we analysed 322 ewes distributed in eight half-sib families. The
      phenotypes studied included two faecal egg counts (LFEC0 and LFEC1), anti
      Teladorsagia circumcincta LIV IgA levels (IgA) and serum pepsinogen levels
      (Peps). RESULTS: The regression analysis revealed one QTL at the 5% genome-wise
      significance level on chromosome 6 for LFEC1 within the marker interval BM4621
      CSN3. This QTL was found to be segregating in three out of the eight families
      analysed. Four other QTL were identified at the 5% chromosome-wise level on
      chromosomes 1, 10 and 14. Three of these QTL influenced faecal egg count, and the
      other one had an effect on IgA levels. CONCLUSION: This study has successfully
      identified segregating QTL for parasite resistance traits in a commercial
      population. For some of the QTL detected, we have identified interesting
      coincidences with QTL previously reported in sheep, although most of those
      studies have been focused on young animals. Some of these coincidences might
      indicate that some common underlying loci affect parasite resistance traits in
      different sheep breeds. The identification of new QTL may suggest the existence
      of complex host-parasite relationships that have unique features depending on the
      host-parasite combination, perhaps due to the different mechanisms underlying
      resistance in adult sheep (hypersensitivity reactions) and lambs (immunity). The
      most significant QTL identified on chromosome 6 for LFEC(1) may be the target for
      future fine-mapping research efforts.

PMID- 19863787
TI  - Characterization of the amyloid bacterial inclusion bodies of the HET-s fungal
      prion.
AB  - The formation of amyloid aggregates is related to the onset of a number of human
      diseases. Recent studies provide compelling evidence for the existence of related
      fibrillar structures in bacterial inclusion bodies (IBs). Bacteria might thus
      provide a biologically relevant and tuneable system to study amyloid aggregation
      and how to interfere with it. Particularly suited for such studies are protein
      models for which structural information is available in both IBs and amyloid
      states. The only high-resolution structure of an infectious amyloid state
      reported to date is that of the HET-s prion forming domain (PFD). Importantly,
      recent solid-state NMR data indicates that the structure of HET-s PFD in IBs
      closely resembles that of the infectious fibrils. Here we present an exhaustive
      conformational characterization of HET-s IBs in order to establish the
      aggregation of this prion in bacteria as a consistent cellular model in which the
      effect of autologous or heterologous protein quality machineries and/or anti
      aggregational and anti-prionic drugs can be further studied.

PMID- 19863788
TI  - Reviewing the literature on access to prompt and effective malaria treatment in
      Kenya: implications for meeting the Abuja targets.
AB  - BACKGROUND: Effective case management is central to reducing malaria mortality
      and morbidity worldwide, but only a minority of those affected by malaria, have
      access to prompt effective treatment.In Kenya, the Division of Malaria Control is
      committed to ensuring that 80 percent of childhood fevers are treated with
      effective anti-malarial medicines within 24 hours of fever onset, but this target
      is largely unmet. This review aimed to document evidence on access to effective
      malaria treatment in Kenya, identify factors that influence access, and make
      recommendations on how to improve prompt access to effective malaria treatment.
      Since treatment-seeking patterns for malaria are similar in many settings in sub
      Saharan Africa, the findings presented in this review have important lessons for
      other malaria endemic countries. METHODS: Internet searches were conducted in
      PUBMED (MEDLINE) and HINARI databases using specific search terms and strategies.
      Grey literature was obtained by soliciting reports from individual researchers
      working in the treatment-seeking field, from websites of major organizations
      involved in malaria control and from international reports. RESULTS: The review
      indicated that malaria treatment-seeking occurs mostly in the informal sector;
      that most fevers are treated, but treatment is often ineffective. Irrational drug
      use was identified as a problem in most studies, but determinants of this
      behaviour were not documented. Availability of non-recommended medicines over-the
      counter and the presence of substandard anti-malarials in the market are well
      documented. Demand side determinants of access include perception of illness
      causes, severity and timing of treatment, perceptions of treatment efficacy,
      simplicity of regimens and ability to pay. Supply side determinants include
      distance to health facilities, availability of medicines, prescribing and
      dispensing practices and quality of medicines. Policy level factors are around
      the complexity and unclear messages regarding drug policy changes. CONCLUSION:
      Kenya, like many other African countries, is still far from achieving the Abuja
      targets. The government, with support from donors, should invest adequately in
      mechanisms that promote access to effective treatment. Such approaches should
      focus on factors influencing multiple dimensions of access and will require the
      cooperation of all stakeholders working in malaria control.

PMID- 19863789
TI  - Comparison of different methods for delayed post-mortem diagnosis of falciparum
      malaria.
AB  - BACKGROUND: Between 10,000 and 12,000 cases of imported malaria are notified in
      the European Union each year. Despite an excellent health care system, fatalities
      do occur. In case of advanced autolysis, the post-mortem diagnostic is impaired.
      Quicker diagnosis could be achieved by using rapid diagnostic malaria tests.
      METHODS: In order to evaluate different methods for the post-mortem diagnosis of
      Plasmodium falciparum malaria in non-immunes, a study was performed on the basis
      of forensic autopsies of corpses examined at variable intervals after death in
      five cases of fatal malaria (with an interval of four hours to five days), and in
      20 cases of deaths unrelated to malaria. Detection of parasite DNA by PCR and an
      immunochromatographic test (ICT) based upon the detection of P. falciparum
      histidine-rich protein 2 (PfHRP2) were compared with the results of microscopic
      examination of smears from cadaveric blood, histopathological findings, and
      autopsy results. RESULTS: In all cases of fatal malaria, post-mortem findings
      were unsuspicious for the final diagnosis, and autoptic investigations, including
      histopathology, were only performed because of additional information by police
      officers and neighbours. Macroscopic findings during autopsy were unspecific.
      Histopathology confirmed sequestration of erythrocytes and pigment in macrophages
      in most organs in four patients (not evaluable in one patient due to autolysis).
      Microscopy of cadaveric blood smears revealed remnants of intraerythrocytic
      parasites, and was compromised or impossible due to autolysis in two cases. PCR
      and ICT performed with cadaveric blood were positive in all malaria patients and
      negative in all controls. CONCLUSION: In non-immune fatalities with unclear
      anamnesis, ICT can be recommended as a sensitive and specific tool for post
      mortem malaria diagnosis, which is easier and faster than microscopy, and also
      applicable when microscopic examination is impossible due to autolysis. PCR is
      more expensive and time-consuming, but may be used as confirmatory test. In
      highly endemic areas where asymptomatic parasitaemia is common, confirmation of
      the diagnosis of malaria as the cause of death has to rely on histopathological
      findings.

PMID- 19863790
TI  - The first Swedish H1N2 swine influenza virus isolate represents an uncommon
      reassortant.
AB  - The European swine influenza viruses (SIVs) show considerable diversity
      comprising different types of H1N1, H3N2, and H1N2 strains. The intensifying full
      genome sequencing efforts reveal further reassortants within these subtypes. Here
      we report the identification of an uncommon reassortant variant of H1N2 subtype
      influenza virus isolated from a pig in a multisite herd where H1N2 swine
      influenza was diagnosed for the first time in Sweden during the winter of 2008
      2009. The majority of the European H1N2 swine influenza viruses described so far
      possess haemagglutinin (HA) of the human-like H1N2 SIV viruses and the
      neuraminidase (NA) of either the European H1N2 or H3N2 SIV-like viruses. The
      Swedish isolate has an avian-like SIV HA and a H3N2 SIV-like NA, which is
      phylogenetically more closely related to H3N2 SIV NAs from isolates collected in
      the early '80s than to the NA of H3N2 origin of the H1N2 viruses isolated during
      the last decade, as depicted by some German strains, indicative of independent
      acquisition of the NA genes for these two types of reassortants. The internal
      genes proved to be entirely of avian-like SIV H1N1 origin. The prevalence of this
      SIV variant in pig populations needs to be determined, as well as the suitability
      of the routinely used laboratory reagents to analyze this strain.The description
      of this H1N2 SIV adds further information to influenza epidemiology and supports
      the necessity of surveillance for influenza viruses in pigs.

PMID- 19863791
TI  - Comparison of breast cancer survival in two populations: Ardabil, Iran and
      British Columbia, Canada.
AB  - BACKGROUND: Patterns in survival can provide information about the burden and
      severity of cancer, help uncover gaps in systemic policy and program delivery,
      and support the planning of enhanced cancer control systems. The aim of this
      paper is to describe the one-year survival rates for breast cancer in two
      populations using population-based cancer registries: Ardabil, Iran, and British
      Columbia (BC), Canada. METHODS: All newly diagnosed cases of female breast cancer
      were identified in the Ardabil cancer registry from 2003 to 2005 and the BC
      cancer registry for 2003. The International Classification of Disease for
      Oncology (ICDO) was used for coding cancer morphology and topography. Survival
      time was determined from cancer diagnosis to death. Age-specific one-year
      survival rates, relative survival rates and weighted standard errors were
      calculated using life-tables for each country. RESULTS: Breast cancer patients in
      BC had greater one-year survival rates than patients in Ardabil overall and for
      each age group under 60. CONCLUSION: These findings support the need for breast
      cancer screening programs (including regular clinical breast examinations and
      mammography), public education and awareness regarding early detection of breast
      cancer, and education of health care providers.

PMID- 19863792
TI  - Assessing the burden of pregnancy-associated malaria under changing transmission
      settings.
AB  - BACKGROUND: The clinical presentation of pregnancy-associated malaria, or PAM,
      depends crucially on the particular epidemiological settings. This can
      potentially lead to an underestimation of its overall burden on the female
      population, especially in regions prone to epidemic outbreaks and where malaria
      transmission is generally low. METHODS: Here, by re-examining historical data, it
      is demonstrated how excess female mortality can be used to evaluate the burden of
      PAM. A simple mathematical model is then developed to highlight the contrasting
      signatures of PAM within the endemicity spectrum and to show how PAM is
      influenced by the intensity and stability of transmission. RESULTS: Both the data
      and the model show that maternal malaria has a huge impact on the female
      population. This is particularly pronounced in low-transmission settings during
      epidemic outbreaks where excess female mortality/morbidity can by far exceed that
      of a similar endemic setting. CONCLUSION: The results presented here call for
      active intervention measures not only in highly endemic regions but also, or in
      particular, in areas where malaria transmission is low and seasonal.

PMID- 19863793
TI  - AIR: A batch-oriented web program package for construction of supermatrices ready
      for phylogenomic analyses.
AB  - BACKGROUND: Large multigene sequence alignments have over recent years been
      increasingly employed for phylogenomic reconstruction of the eukaryote tree of
      life. Such supermatrices of sequence data are preferred over single gene
      alignments as they contain vastly more information about ancient sequence
      characteristics, and are thus more suitable for resolving deeply diverging
      relationships. However, as alignments are expanded, increasingly numbers of sites
      with misleading phylogenetic information are also added. Therefore, a major goal
      in phylogenomic analyses is to maximize the ratio of information to noise; this
      can be achieved by the reduction of fast evolving sites. RESULTS: Here we present
      a batch-oriented web-based program package, named AIR that allows 1)
      transformation of several single genes to one multigene alignment, 2)
      identification of evolutionary rates in multigene alignments and 3) removal of
      fast evolving sites. These three processes can be done with the programs AIR
      Appender, AIR-Identifier, and AIR-Remover (AIR), which can be used independently
      or in a semi-automated pipeline. AIR produces user-friendly output files with
      filtered and non-filtered alignments where residues are colored according to
      their evolutionary rates. Other bioinformatics applications linked to the AIR
      package are available at the Bioportal http://www.bioportal.uio.no, University of
      Oslo; together these greatly improve the flexibility, efficiency and quality of
      phylogenomic analyses. CONCLUSION: The AIR program package allows for efficient
      creation of multigene alignments and better assessment of evolutionary rates in
      sequence alignments. Removing fast evolving sites with the AIR programs has been
      employed in several recent phylogenomic analyses resulting in improved
      phylogenetic resolution and increased statistical support for branching patterns
      among the early diverging eukaryotes.

PMID- 19863794
TI  - A heritable component in sex ratio and caste determination in a Cardiocondyla
      ant.
AB  - Studies on sex ratios in social insects provide among the most compelling
      evidence for the importance of kin selection in social evolution. The elegant
      synthesis of Fisher's sex ratio principle and Hamilton's inclusive fitness theory
      predicts that colony-level sex ratios vary with the colonies' social and genetic
      structures. Numerous empirical studies in ants, bees, and wasps have corroborated
      these predictions. However, the evolutionary optimization of sex ratios requires
      genetic variation, but one fundamental determinant of sex ratios - the propensity
      of female larvae to develop into young queens or workers ("queen bias") - is
      thought to be largely controlled by the environment. Evidence for a genetic
      influence on sex ratio and queen bias is as yet restricted to a few taxa, in
      particular hybrids.Because of the very short lifetime of their queens, ants of
      the genus Cardiocondyla are ideal model systems for the study of complete
      lifetime reproductive success, queen bias, and sex ratios. We found that lifetime
      sex ratios of the ant Cardiocondyla kagutsuchi have a heritable component. In
      experimental single-queen colonies, 22 queens from a genetic lineage with a
      highly female-biased sex ratio produced significantly more female-biased
      offspring sex ratios than 16 queens from a lineage with a more male-biased sex
      ratio (median 91.5% vs. 58.5% female sexuals). Sex ratio variation resulted from
      different likelihood of female larvae developing into sexuals (median 50% vs.
      22.6% female sexuals) even when uniformly nursed by workers from another
      colony.Consistent differences in lifetime sex ratios and queen bias among queens
      of C. kagutsuchi suggest that heritable, genetic or maternal effects strongly
      affect caste determination. Such variation might provide the basis for adaptive
      evolution of queen and worker strategies, though it momentarily constrains the
      power of workers and queens to optimize caste ratios.

PMID- 19863795
TI  - Local indicators of geocoding accuracy (LIGA): theory and application.
AB  - BACKGROUND: Although sources of positional error in geographic locations (e.g.
      geocoding error) used for describing and modeling spatial patterns are widely
      acknowledged, research on how such error impacts the statistical results has been
      limited. In this paper we explore techniques for quantifying the perturbability
      of spatial weights to different specifications of positional error. RESULTS: We
      find that a family of curves describes the relationship between perturbability
      and positional error, and use these curves to evaluate sensitivity of alternative
      spatial weight specifications to positional error both globally (when all
      locations are considered simultaneously) and locally (to identify those locations
      that would benefit most from increased geocoding accuracy). We evaluate the
      approach in simulation studies, and demonstrate it using a case-control study of
      bladder cancer in south-eastern Michigan. CONCLUSION: Three results are
      significant. First, the shape of the probability distributions of positional
      error (e.g. circular, elliptical, cross) has little impact on the perturbability
      of spatial weights, which instead depends on the mean positional error. Second,
      our methodology allows researchers to evaluate the sensitivity of spatial
      statistics to positional accuracy for specific geographies. This has substantial
      practical implications since it makes possible routine sensitivity analysis of
      spatial statistics to positional error arising in geocoded street addresses,
      global positioning systems, LIDAR and other geographic data. Third, those
      locations with high perturbability (most sensitive to positional error) and high
      leverage (that contribute the most to the spatial weight being considered) will
      benefit the most from increased positional accuracy. These are rapidly identified
      using a new visualization tool we call the LIGA scatterplot.Herein lies a paradox
      for spatial analysis: For a given level of positional error increasing sample
      density to more accurately follow the underlying population distribution
      increases perturbability and introduces error into the spatial weights matrix. In
      some studies positional error may not impact the statistical results, and in
      others it might invalidate the results. We therefore must understand the
      relationships between positional accuracy and the perturbability of the spatial
      weights in order to have confidence in a study's results.

PMID- 19863796
TI  - A simple, flexible and efficient PCR-fusion/Gateway cloning procedure for gene
      fusion, site-directed mutagenesis, short sequence insertion and domain deletions
      and swaps.
AB  - BACKGROUND: The progress and completion of various plant genome sequencing
      projects has paved the way for diverse functional genomic studies that involve
      cloning, modification and subsequent expression of target genes. This requires
      flexible and efficient procedures for generating binary vectors containing: gene
      fusions, variants from site-directed mutagenesis, addition of protein tags
      together with domain swaps and deletions. Furthermore, efficient cloning
      procedures, ideally high throughput, are essential for pyramiding of multiple
      gene constructs. RESULTS: Here, we present a simple, flexible and efficient PCR
      fusion/Gateway cloning procedure for construction of binary vectors for a range
      of gene fusions or variants with single or multiple nucleotide substitutions,
      short sequence insertions, domain deletions and swaps. Results from selected
      applications of the procedure which include ORF fusion, introduction of Cys>Ser
      mutations, insertion of StrepII tag sequence and domain swaps for Arabidopsis
      secondary cell wall AtCesA genes are demonstrated. CONCLUSION: The PCR
      fusion/Gateway cloning procedure described provides an elegant, simple and
      efficient solution for a wide range of diverse and complicated cloning tasks.
      Through streamlined cloning of sets of gene fusions and modification variants
      into binary vectors for systematic functional studies of gene families, our
      method allows for efficient utilization of the growing sequence and expression
      data.

PMID- 19863798
TI  - ArrayMining: a modular web-application for microarray analysis combining ensemble
      and consensus methods with cross-study normalization.
AB  - BACKGROUND: Statistical analysis of DNA microarray data provides a valuable
      diagnostic tool for the investigation of genetic components of diseases. To take
      advantage of the multitude of available data sets and analysis methods, it is
      desirable to combine both different algorithms and data from different studies.
      Applying ensemble learning, consensus clustering and cross-study normalization
      methods for this purpose in an almost fully automated process and linking
      different analysis modules together under a single interface would simplify many
      microarray analysis tasks. RESULTS: We present ArrayMining.net, a web-application
      for microarray analysis that provides easy access to a wide choice of feature
      selection, clustering, prediction, gene set analysis and cross-study
      normalization methods. In contrast to other microarray-related web-tools,
      multiple algorithms and data sets for an analysis task can be combined using
      ensemble feature selection, ensemble prediction, consensus clustering and cross
      platform data integration. By interlinking different analysis tools in a modular
      fashion, new exploratory routes become available, e.g. ensemble sample
      classification using features obtained from a gene set analysis and data from
      multiple studies. The analysis is further simplified by automatic parameter
      selection mechanisms and linkage to web tools and databases for functional
      annotation and literature mining. CONCLUSION: ArrayMining.net is a free web
      application for microarray analysis combining a broad choice of algorithms based
      on ensemble and consensus methods, using automatic parameter selection and
      integration with annotation databases.

PMID- 19863799
TI  - Can foot anthropometric measurements predict dynamic plantar surface contact
      area?
AB  - BACKGROUND: Previous studies have suggested that increased plantar surface area,
      associated with pes planus, is a risk factor for the development of lower
      extremity overuse injuries. The intent of this study was to determine if a single
      or combination of foot anthropometric measures could be used to predict plantar
      surface area. METHODS: Six foot measurements were collected on 155 subjects (97
      females, 58 males, mean age 24.5 +/- 3.5 years). The measurements as well as one
      ratio were entered into a stepwise regression analysis to determine the optimal
      set of measurements associated with total plantar contact area either including
      or excluding the toe region. The predicted values were used to calculate plantar
      surface area and were compared to the actual values obtained dynamically using a
      pressure sensor platform. RESULTS: A three variable model was found to describe
      the relationship between the foot measures/ratio and total plantar contact area
      (R2 = 0.77, p < 0.0001)). A three variable model was also found to describe the
      relationship between the foot measures/ratio and plantar contact area minus the
      toe region (R2 = 0.76, p < 0.0001). CONCLUSION: The results of this study
      indicate that the clinician can use a combination of simple, reliable, and time
      efficient foot anthropometric measurements to explain over 75% of the plantar
      surface contact area, either including or excluding the toe region.

PMID- 19863797
TI  - Analysis of knockout mice suggests a role for VGF in the control of fat storage
      and energy expenditure.
AB  - BACKGROUND: Previous studies of mixed background mice have demonstrated that
      targeted deletion of Vgf produces a lean, hypermetabolic mouse that is resistant
      to diet-, lesion-, and genetically-induced obesity. To investigate potential
      mechanism(s) and site(s) of action of VGF, a neuronal and endocrine secreted
      protein and neuropeptide precursor, we further analyzed the metabolic phenotypes
      of two independent VGF knockout lines on C57Bl6 backgrounds. RESULTS: Unlike
      hyperactive VGF knockout mice on a mixed C57Bl6-129/SvJ background, homozygous
      mutant mice on a C57Bl6 background were hypermetabolic with similar locomotor
      activity levels to Vgf+/Vgf+ mice, during day and night cycles, indicating that
      mechanism(s) other than hyperactivity were responsible for their increased energy
      expenditure. In Vgf-/Vgf- knockout mice, morphological analysis of brown and
      white adipose tissues (BAT and WAT) indicated decreased fat storage in both
      tissues, and decreased adipocyte perimeter and area in WAT. Changes in gene
      expression measured by real-time RT-PCR were consistent with increased fatty acid
      oxidation and uptake in BAT, and increased lipolysis, decreased lipogenesis, and
      brown adipocyte differentiation in WAT, suggesting that increased sympathetic
      nervous system activity in Vgf-/Vgf- mice may be associated with or responsible
      for alterations in energy expenditure and fat storage. In addition, uncoupling
      protein 1 (UCP1) and UCP2 protein levels, mitochondrial number, and mitochondrial
      cristae density were upregulated in Vgf-/Vgf- BAT. Using immunohistochemical and
      histochemical techniques, we detected VGF in nerve fibers innervating BAT and Vgf
      promoter-driven reporter expression in cervical and thoracic spinal ganglia that
      project to and innervate the chest wall and tissues including BAT. Moreover, VGF
      peptide levels were quantified by radioimmunoassay in BAT, and were found to be
      down-regulated by a high fat diet. Lastly, despite being hypermetabolic, VGF
      knockout mice were cold intolerant. CONCLUSION: We propose that VGF and/or VGF
      derived peptides modulate sympathetic outflow pathways to regulate fat storage
      and energy expenditure.

PMID- 19863800
TI  - Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2
      genes in yeast.
AB  - BACKGROUND: Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations
      in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer
      (HNPCC). Because not all MLH1 alterations result in loss of MMR function,
      accurate characterization of variants and their classification in terms of their
      effect on MMR function is essential for reliable genetic testing and effective
      treatment. To date, in vivo assays for functional characterization of MLH1
      mutations performed in various model systems have used episomal expression of the
      modified MMR genes. We describe here a novel approach to determine accurately the
      functional significance of hMLH1 mutations in vivo, based on co-expression of
      human MLH1 and PMS2 in yeast cells. METHODS: Yeast MLH1 and PMS1 genes, whose
      protein products form the MutLalpha complex, were replaced by human orthologs
      directly on yeast chromosomes by homologous recombination, and the resulting MMR
      activity was tested. RESULTS: The yeast strain co-expressing hMLH1 and hPMS2
      exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1
      variants were introduced, using the same approach, into the prepared yeast model,
      and their effect on MMR function was determined. Five variants (A92P, S93G,
      I219V, K618R and K618T) were classified as non-pathogenic, whereas variants
      T117M, Y646C and R659Q were characterized as pathogenic. CONCLUSION: Results of
      our in vivo yeast-based approach correlate well with clinical data in five out of
      seven hMLH1 variants and the described model was thus shown to be useful for
      functional characterization of MLH1 variants in cancer patients found throughout
      the entire coding region of the gene.

PMID- 19863801
TI  - Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining
      two amino acids originates from bicarbonate.
AB  - BACKGROUND: Syringolin A, an important virulence factor in the interaction of the
      phytopathogenic bacterium Pseudomonas syringae pv. syringae B728a with its host
      plant Phaseolus vulgaris (bean), was recently shown to irreversibly inhibit
      eukaryotic proteasomes by a novel mechanism. Syringolin A is synthesized by a
      mixed non-ribosomal peptide synthetase/polyketide synthetase and consists of a
      tripeptide part including a twelve-membered ring with an N-terminal valine that
      is joined to a second valine via a very unusual ureido group. Analysis of
      sequence and architecture of the syringolin A synthetase gene cluster with the
      five open reading frames sylA-sylE allowed to formulate a biosynthesis model that
      explained all structural features of the tripeptide part of syringolin A but left
      the biosynthesis of the unusual ureido group unaccounted for. RESULTS: We have
      cloned a 22 kb genomic fragment containing the sylA-sylE gene cluster but no
      other complete gene into the broad host range cosmid pLAFR3. Transfer of the
      recombinant cosmid into Pseudomonas putida and P. syringae pv. syringae SM was
      sufficient to direct the biosynthesis of bona fide syringolin A in these
      heterologous organisms whose genomes do not contain homologous genes. NMR
      analysis of syringolin A isolated from cultures grown in the presence of
      NaH(13)CO(3) revealed preferential (13)C-labeling at the ureido carbonyl
      position. CONCLUSION: The results show that no additional syringolin A-specific
      genes were needed for the biosynthesis of the enigmatic ureido group joining two
      amino acids. They reveal the source of the ureido carbonyl group to be
      bicarbonate/carbon dioxide, which we hypothesize is incorporated by carbamylation
      of valine mediated by the sylC gene product(s). A similar mechanism may also play
      a role in the biosynthesis of other ureido-group-containing NRPS products known
      largely from cyanobacteria.

PMID- 19863802
TI  - Relationship between B-type natriuretic peptide levels and echocardiographic
      indices of left ventricular filling pressures in post-cardiac surgery patients.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is increased in post-cardiac surgery
      patients, however the mechanisms underlying BNP release are still unclear. In the
      current study, we aimed to assess the relationship between postoperative BNP
      levels and left ventricular filling pressures in post-cardiac surgery patients.
      METHODS: We prospectively enrolled 134 consecutive patients referred to our
      Center 8 +/- 5 days after cardiac surgery. BNP was sampled at hospital admission
      and related to the following echocardiographic parameters: left ventricular (LV)
      diastolic volume (DV), LV systolic volume (SV), LV ejection fraction (EF), LV
      mass, relative wall thickness (RWT), indexed left atrial volume (iLAV), mitral
      inflow E/A ratio, mitral E wave deceleration time (DT), ratio of the transmitral
      E wave to the Doppler tissue early mitral annulus velocity (E/E'). RESULTS: A
      total of 124 patients had both BNP and echocardiographic data. The BNP values
      were significantly elevated (mean 353 +/- 356 pg/ml), with normal value in only
      17 patients (13.7%). Mean LVEF was 59 +/- 10% (LVEF >or=50% in 108 pts). There
      was no relationship between BNP and LVEF (p = 0.11), LVDV (p = 0.88), LVSV (p =
      0.50), E/A (p = 0.77), DT (p = 0.33) or RWT (p = 0.50). In contrast, BNP was
      directly related to E/E' (p < 0.001), LV mass (p = 0.006) and iLAV (p = 0.026).
      At multivariable regression analysis, age and E/E' were the only independent
      predictors of BNP levels. CONCLUSION: In post-cardiac surgery patients with
      overall preserved LV systolic function, the significant increase in BNP levels is
      related to E/E', an echocardiographic parameter of elevated LV filling pressures
      which indicates left atrial pressure as a major determinant in BNP release in
      this clinical setting.

PMID- 19863804
TI  - Ultrasonographic screening of urinary schistosomiasis infected patients in Agulu
      community, Anambra state, southeast Nigeria.
AB  - BACKGROUND: The pathology of Schistosoma haematobium infection in 60 infected
      primary school children in Agulu community, Anambra State, southeast Nigeria,
      with over 50 ova/10 ml urine was assessed. METHODS: The ultrasonographic
      examination was done using a sector scanner with convex probe. World Health
      Organisation method was used for classification and scoring of lesions. T-test
      and Coefficient of determination were used in analysis. RESULTS: The pathologic
      effects due to S. haematobuim identified among the study group included
      irregularity of the bladder wall (25%), thickening of the bladder wall (10%) and
      massing of the bladder wall (3.3%). About 4(6.7%) and 1(1.7%) of the patients had
      the right pelvis and left pelvis of their kidney moderately dilated respectively.
      Identified bladder wall lesions had 69 scores while kidney dilation had 30
      scores. The number of individuals with lesions correlated with intensity of
      infection. Male pupils (65.2%) had more lesions than females (34.8%). The
      difference observed in lesion distribution among males and females was found to
      be significant (df = 6, p < 0.05). All bladder and kidney lesions responded
      favorably to treatment with praziquantel (40 mg/kg-body weight). CONCLUSION:
      Health education campaign including showing the community members evidence of
      damages to the organs (from the ultrasound pictures) will go a long way in the
      control and prevention of the disease in this community.

PMID- 19863803
TI  - Malaria treatment perceptions, practices and influences on provider behaviour:
      comparing hospitals and non-hospitals in south-east Nigeria.
AB  - BACKGROUND: People seek treatment for malaria from a wide range of providers
      ranging from itinerant drug sellers to hospitals. However, there are lots of
      problems with treatment provision. Hence, factors influencing treatment provision
      in hospitals and non-hospitals require further investigation in order to remedy
      the situation. OBJECTIVES: To examine the knowledge, pattern of treatment
      provision and factors influencing the behaviour of hospitals and non-hospitals in
      the treatment of malaria, so as to identify loci for interventions to improve
      treatment of the disease. METHODS: A pre-tested structured questionnaire was used
      to collect data from 225 providers from hospitals and non-hospitals about their
      malaria treatment practices and factors that influence their provision of malaria
      treatment services in south-east Nigeria. The data from hospitals and other
      providers were compared for systematic differences. RESULTS: 73.5% of hospitals
      used microscopy to diagnose malaria and only 34.5.1% of non-hospitals did (p <
      0.05). Majority of the respondents considered ability to pay bills (35.2%),
      already existing relationship (9.4%) and body mechanism (35.2%) of the patient
      before they provided malaria treatment services. Pressure from wholesalers to
      providers to repay the cost of supplied drugs was the major influence of the type
      of drugs provided to patients. CONCLUSION: There are many challenges to
      appropriate provision of malaria treatment services, although challenges are less
      in hospitals compared to other types of non-hospitals. Improving proper diagnosis
      of malaria and improving the knowledge of providers about malaria are
      interventions that could be used to improve malaria treatment provision.

PMID- 19863805
TI  - Selenoproteins regulate macrophage invasiveness and extracellular matrix-related
      gene expression.
AB  - BACKGROUND: Selenium, a micronutrient whose deficiency in diet causes immune
      dysfunction and inflammatory disorders, is thought to exert its physiological
      effects mostly in the form of selenium-containing proteins (selenoproteins).
      Incorporation of selenium into the amino acid selenocysteine (Sec), and
      subsequently into selenoproteins is mediated by Sec tRNA([Ser]Sec). RESULTS: To
      define macrophage-specific selenoprotein functions, we generated mice with the
      Sec tRNA([Ser]Sec) gene specifically deleted in myeloid cells. These mutant mice
      were devoid of the "selenoproteome" in macrophages, yet exhibited largely normal
      inflammatory responses. However, selenoprotein deficiency led to aberrant
      expression of extracellular matrix-related genes, and diminished migration of
      macrophages in a protein gel matrix. CONCLUSION: Selenium status may affect
      immune defense and tissue homeostasis through its effect on selenoprotein
      expression and the trafficking of tissue macrophages.

PMID- 19863806
TI  - The development of 3-D, in vitro, endothelial culture models for the study of
      coronary artery disease.
AB  - The response of the vascular endothelium to wall shear stress plays a central
      role in the development and progression of atherosclerosis. Current studies have
      investigated endothelial response using idealized in vitro flow chambers. Such
      cell culture models are unable to accurately replicate the complex in vivo wall
      shear stress patterns arising from anatomical geometries. To better understand
      this implication, we have created both simplified/tubular and anatomically
      realistic in vitro endothelial flow models of the human right coronary artery. A
      post-mortem vascular cast of the human left ventricular outflow tract was used to
      create geometrically accurate silicone elastomer models. Straight, tubular models
      were created using a custom made mold. Following the culture of human abdominal
      aortic endothelial cells within the inner lumen, cells were exposed to steady
      flow (Re = 233) for varying time periods. The resulting cell morphology was
      analyzed in terms of shape index and angle of orientation relative to the flow
      direction. In both models a progressive elongation and alignment of the
      endothelium in the flow direction was observed following 8, 12, and 24 hours.
      This change, however, was significantly less pronounced in the anatomical model
      (as observed from morphological variations indicative of localized flow
      features). Differences were also observed between the inner and outer walls at
      the disease-prone proximal region. Since morphological adaptation is a visual
      indication of endothelial shear stress activation, the use of anatomical models
      in endothelial genetic and biochemical studies may offer better insight into the
      disease process.

PMID- 19863807
TI  - Toxicology of Nanomaterials: Permanent interactive learning.
AB  - Particle and Fibre Toxicology wants to play a decisive role in a time where
      particle research is challenged and driven by the developments and applications
      of nanomaterials. This aim is not merely quantitative in publishing a given
      number of papers on nanomaterials, but also qualitatively since the field of
      nanotoxicology is rapidly emerging and benchmarks for good science are needed.
      Since then a number of things have happened that merit further analysis. The
      interactive learning issue is best shown by report and communications on the
      toxicology of multi-wall carbon nanotubes (CNT). A special workshop on the CNT
      has now been organized twice in Nagano (Japan) and this editorial contains a
      summary of the most important outcomes. Finally, we take the opportunity discuss
      some recent reports from the nanotech literature, and more specifically a Chinese
      study that claims severe consequences of nanoparticle exposure.

PMID- 19863809
TI  - Evaluating the informatics for integrating biology and the bedside system for
      clinical research.
AB  - BACKGROUND: Selecting patient cohorts is a critical, iterative, and often time
      consuming aspect of studies involving human subjects; informatics tools for
      helping streamline the process have been identified as important infrastructure
      components for enabling clinical and translational research. We describe the
      evaluation of a free and open source cohort selection tool from the Informatics
      for Integrating Biology and the Bedside (i2b2) group: the i2b2 hive. METHODS: Our
      evaluation included the usability and functionality of the i2b2 hive using
      several real world examples of research data requests received electronically at
      the University of Utah Health Sciences Center between 2006 - 2008. The hive
      server component and the visual query tool application were evaluated for their
      suitability as a cohort selection tool on the basis of the types of data elements
      requested, as well as the effort required to fulfill each research data request
      using the i2b2 hive alone. RESULTS: We found the i2b2 hive to be suitable for
      obtaining estimates of cohort sizes and generating research cohorts based on
      simple inclusion/exclusion criteria, which consisted of about 44% of the clinical
      research data requests sampled at our institution. Data requests that relied on
      post-coordinated clinical concepts, aggregate values of clinical findings, or
      temporal conditions in their inclusion/exclusion criteria could not be fulfilled
      using the i2b2 hive alone, and required one or more intermediate data steps in
      the form of pre- or post-processing, modifications to the hive metadata, etc.
      CONCLUSION: The i2b2 hive was found to be a useful cohort-selection tool for
      fulfilling common types of requests for research data, and especially in the
      estimation of initial cohort sizes. For another institution that might want to
      use the i2b2 hive for clinical research, we recommend that the institution would
      need to have structured, coded clinical data and metadata available that can be
      transformed to fit the logical data models of the i2b2 hive, strategies for
      extracting relevant clinical data from source systems, and the ability to perform
      substantial pre- and post-processing of these data.

PMID- 19863808
TI  - Influences of naturally occurring agents in combination with fluoride on gene
      expression and structural organization of Streptococcus mutans in biofilms.
AB  - BACKGROUND: The association of specific bioactive flavonoids and terpenoids with
      fluoride can modulate the development of cariogenic biofilms by simultaneously
      affecting the synthesis of exopolysaccharides (EPS) and acid production by
      Streptococcus mutans, which enhanced the cariostatic effectiveness of fluoride in
      vivo. In the present study, we further investigated whether the biological
      actions of combinations of myricetin (flavonoid), tt-farnesol (terpenoid) and
      fluoride can influence the expression of specific genes of S. mutans within
      biofilms and their structural organization using real-time PCR and confocal
      fluorescence microscopy. RESULTS: Twice-daily treatment (one-minute exposure)
      during biofilm formation affected the gene expression by S. mutans both at early
      (49-h) and later (97-h) stages of biofilm development. Biofilms treated with
      combination of agents displayed lower mRNA levels for gtfB and gtfD (associated
      with exopolysaccharides synthesis) and aguD (associated with S. mutans acid
      tolerance) than those treated with vehicle-control (p < 0.05). Furthermore,
      treatment with combination of agents markedly affected the structure-architecture
      of S. mutans biofilms by reducing the biovolume (biomass) and proportions of both
      EPS and bacterial cells across the biofilm depth, especially in the middle and
      outer layers (vs. vehicle-control, p < 0.05). The biofilms treated with
      combination of agents were also less acidogenic, and had reduced amounts of
      extracellular insoluble glucans and intracellular polysaccharides than vehicle
      treated biofilms (p < 0.05). CONCLUSION: The data show that the combination of
      naturally-occurring agents with fluoride effectively disrupted the expression of
      specific virulence genes, structural organization and accumulation of S. mutans
      biofilms, which may explain the enhanced cariostatic effect of our
      chemotherapeutic approach.

PMID- 19863810
TI  - RAD51 paralogs promote homology-directed repair at diversifying immunoglobulin V
      regions.
AB  - BACKGROUND: Gene conversion depends upon the same factors that carry out more
      general process of homologous recombination, including homologous gene targeting
      and recombinational repair. Among these are the RAD51 paralogs, conserved factors
      related to the key recombination factor, RAD51. In chicken and other fowl, gene
      conversion (templated mutation) diversifies immunoglobulin variable region
      sequences. This allows gene conversion and recombinational repair to be studied
      using the chicken DT40 B cell line, which carries out constitutive gene
      conversion and provides a robust and physiological model for homology-directed
      repair in vertebrate cells. RESULTS: We show that DT40 contains constitutive
      nuclear foci of the repair factors RAD51D and XRCC2, consistent with activated
      homologous recombination. Single-cell imaging of a DT40 derivative in which the
      rearranged and diversifying immunoglobulin lambdaR light chain gene is tagged
      with polymerized lactose operator, DT40 PolyLacO-lambdaR, showed that RAD51D and
      XRCC2 localize to the diversifying lambdaR gene. Colocalizations correlate both
      functionally and physically with active immunoglobulin gene conversion. Ectopic
      expression of either RAD51D or XRCC2 accelerated the clonal rate of gene
      conversion, and conversion tracts were significantly longer in RAD51D than XRCC2
      transfectants. CONCLUSION: These results demonstrate direct functions of RAD51D
      and XRCC2 in immunoglobulin gene conversion, and also suggest that modulation of
      levels of repair factors may be a useful strategy to promote gene correction in
      other cell types.

PMID- 19863812
TI  - The use of Edinburgh Postnatal Depression Scale to identify postnatal depression
      symptoms at well child visit.
AB  - OBJECTIVES: 1) to evaluate the role of the pediatrician in detecting postnatal
      depression (PD) symptoms by the Edinburgh Postnatal Depression Scale (EPDS); 2)
      to detect factors increasing the risk of PD and, 3) to assess the importance of
      scores gained from fathers' questionnaire. METHODS: we surveyed 1122 mothers and
      499 fathers who were assessed using the EPDS during the first well-child visit.
      After 5 weeks, high scoring parents, completed a second EPDS. High scoring
      parents were examined by a psychiatrist who had to confirm the PD diagnosis.
      RESULTS: 26.6% of mothers and 12.6% of fathers at the first visit, 19.0% of
      mothers and 9.1% of fathers at the second visit, gained scores signaling the risk
      of PD. Four mothers and two fathers had confirmed PD diagnosis. Younger maternal
      age, non-Italian nationality and low socio-economic condition were related to
      higher EPDS scores. CONCLUSION: PD is common in the average population. Using a
      simple and standardized instrument, pediatricians are able to detect parents with
      higher risk of suffering from PD.

PMID- 19863811
TI  - Annotation, phylogenetics, and expression of the nuclear receptors in Daphnia
      pulex.
AB  - BACKGROUND: The nuclear receptor superfamily currently consists of seven gene
      subfamilies that encompass over 80 distinct receptor proteins. These
      transcription factors typically share a common five-domain structure with a
      highly conserved DNA-binding domain. Some nuclear receptors are ubiquitous among
      the metazoans, while others are unique to specific phylogenetic groups.
      Crustaceans represent the second largest group of arthropods with insects being
      the largest. However, relative to insects, little is known about the nuclear
      receptors of crustaceans. The aim of this study was to identify putative nuclear
      receptors from the first assembled genome of a crustacean Daphnia pulex
      http://wFleaBase.org. Nuclear receptor expression was evaluated and receptors
      were subjected to phylogenetic analyses to gain insight into evolution and
      function. RESULTS: Twenty-five putative nuclear receptors were identified in D.
      pulex based on the presence of a conserved DNA-binding domain. All of the nuclear
      receptor protein sequences contain a highly homologous DNA-binding domain and a
      less conserved ligand-binding domain with the exception of the NR0A group. These
      receptors lack a ligand-binding domain. Phylogenetic analysis revealed the
      presence of all seven receptor subfamilies. The D. pulex genome contains several
      nuclear receptors that have vertebrate orthologs. However, several nuclear
      receptor members that are represented in vertebrates are absent from D. pulex.
      Notable absences include receptors of the 1C group (peroxisome proliferators
      activated receptors), the 3A group (estrogen receptor), and the 3C group
      (androgen, progestogen, mineralcorticoid, and glucocorticoid receptors). The D.
      pulex genome also contains nuclear receptor orthologs that are present in insects
      and nematodes but not vertebrates, including putative nuclear receptors within
      the NR0A group. A novel group of receptors, designated HR97, was identified in D.
      pulex that groups with the HR96/CeNHR8/48/DAF12 clade, but forms its own sub
      clade. Gene products were detected in adult female D. pulex for 21 of the 25
      receptors. CONCLUSION: Nuclear receptors are ancient proteins with highly
      conserved DNA-binding domains. The DNA-binding domains of the nuclear receptors
      of D. pulex contain the same degree of conservation that is typically found
      within nuclear receptors of other species. Most of the receptors identified in D.
      pulex have orthologs within the vertebrate and invertebrate lineages examined
      with the exception of the novel HR97 group and the Dappu-HR10 and potentially the
      Dappu-HR11 receptors found in D. pulex. These groups of receptors may harbour
      functions that are intrinsic to crustacean physiology.

PMID- 19863813
TI  - Proteomics, pathway array and signaling network-based medicine in cancer.
AB  - Cancer is a multifaceted disease that results from dysregulated normal cellular
      signaling networks caused by genetic, genomic and epigenetic alterations at cell
      or tissue levels. Uncovering the underlying protein signaling network changes,
      including cell cycle gene networks in cancer, aids in understanding the molecular
      mechanism of carcinogenesis and identifies the characteristic signaling network
      signatures unique for different cancers and specific cancer subtypes. The
      identified signatures can be used for cancer diagnosis, prognosis, and
      personalized treatment. During the past several decades, the available technology
      to study signaling networks has significantly evolved to include such platforms
      as genomic microarray (expression array, SNP array, CGH array, etc.) and
      proteomic analysis, which globally assesses genetic, epigenetic, and proteomic
      alterations in cancer. In this review, we compared Pathway Array analysis with
      other proteomic approaches in analyzing protein network involved in cancer and
      its utility serving as cancer biomarkers in diagnosis, prognosis and therapeutic
      target identification. With the advent of bioinformatics, constructing high
      complexity signaling networks is possible. As the use of signaling network-based
      cancer diagnosis, prognosis and treatment is anticipated in the near future,
      medical and scientific communities should be prepared to apply these techniques
      to further enhance personalized medicine.

PMID- 19863814
TI  - Incidental detection of an occult oral malignancy with autofluorescence imaging:
      a case report.
AB  - BACKGROUND: Autofluorescence imaging is used widely for diagnostic evaluation of
      various epithelial malignancies. Cancerous lesions display loss of
      autofluorescence due to malignant changes in epithelium and subepithelial stroma.
      Carcinoma of unknown primary site presents with lymph node or distant metastasis,
      for which the site of primary tumour is not detectable. We describe here the use
      of autofluorescence imaging for detecting a clinically innocuous appearing occult
      malignancy of the palate which upon pathological examination was consistent with
      a metastatic squamous cell carcinoma. CASE DESCRIPTION: A submucosal nodule was
      noted on the right posterior hard palate of a 59-year-old white female during
      clinical examination. Examination of this lesion using a multispectral oral
      cancer screening device revealed loss of autofluorescence at 405 nm illumination.
      An excisional biopsy of this nodule, confirmed the presence of a metastatic
      squamous cell carcinoma. Four years ago, this patient was diagnosed with
      metastatic squamous cell carcinoma of the right mid-jugular lymph node of unknown
      primary. She was treated with external beam irradiation and remained disease free
      until current presentation. CONCLUSION: This case illustrates the important role
      played by autofluorescence tissue imaging in diagnosing a metastatic palatal
      tumour that appeared clinically innocuous and otherwise would not have been
      biopsied.

PMID- 19863815
TI  - Raman spectroscopy and advanced mathematical modelling in the discrimination of
      human thyroid cell lines.
AB  - Raman spectroscopy could offer non-invasive, rapid and an objective nature to
      cancer diagnostics. However, much work in this field has focused on resolving
      differences between cancerous and non-cancerous tissues, and lacks the
      reproducibility and interpretation to be put into clinical practice. Much work is
      needed on basic cellular differences between malignancy and normal. This would
      allow the establishment of a clinically relevant cellular based model to
      translate to tissue classification. Raman spectroscopy provides a very detailed
      biochemical analysis of the target material and to 'unlock' this potential
      requires sophisticated mathematical modelling such as neural networks as an
      adjunct to data interpretation. Commercially obtained cancerous and non-cancerous
      cells, cultured in the laboratory were used in Raman spectral measurements. Data
      trends were visualised through PCA and then subjected to neural network analysis
      based on self-organising maps; consisting of m maps, where m is the number of
      classes to be recognised. Each map approximates the statistical distribution of a
      given class. The neural network analysis provided a 95% accuracy for
      identification of the cancerous cell line and 92% accuracy for normal cell line.
      In this preliminary study we have demonstrated th ability to distinguish between
      "normal" and cancerous commercial cell lines. This encourages future work to
      establish the reasons underpinning these spectral differences and to move forward
      to more complex systems involving tissues. We have also shown that the use of
      sophisticated mathematical modelling allows a high degree of discrimination of
      'raw' spectral data.

PMID- 19863816
TI  - Analysis and comparison of very large metagenomes with fast clustering and
      functional annotation.
AB  - BACKGROUND: The remarkable advance of metagenomics presents significant new
      challenges in data analysis. Metagenomic datasets (metagenomes) are large
      collections of sequencing reads from anonymous species within particular
      environments. Computational analyses for very large metagenomes are extremely
      time-consuming, and there are often many novel sequences in these metagenomes
      that are not fully utilized. The number of available metagenomes is rapidly
      increasing, so fast and efficient metagenome comparison methods are in great
      demand. RESULTS: The new metagenomic data analysis method Rapid Analysis of
      Multiple Metagenomes with a Clustering and Annotation Pipeline (RAMMCAP) was
      developed using an ultra-fast sequence clustering algorithm, fast protein family
      annotation tools, and a novel statistical metagenome comparison method that
      employs a unique graphic interface. RAMMCAP processes extremely large datasets
      with only moderate computational effort. It identifies raw read clusters and
      protein clusters that may include novel gene families, and compares metagenomes
      using clusters or functional annotations calculated by RAMMCAP. In this study,
      RAMMCAP was applied to the two largest available metagenomic collections, the
      "Global Ocean Sampling" and the "Metagenomic Profiling of Nine Biomes".
      CONCLUSION: RAMMCAP is a very fast method that can cluster and annotate one
      million metagenomic reads in only hundreds of CPU hours. It is available from
      http://tools.camera.calit2.net/camera/rammcap/.

PMID- 19863817
TI  - Telomere shortening may be associated with human keloids.
AB  - BACKGROUND: Keloids are benign skin tumors that are the effect of a dysregulated
      wound-healing process in genetically predisposed patients. They are inherited
      with an autosomal dominant mode with incomplete clinical penetrance and variable
      expression. Keloids are characterized by formation of excess scar tissue beyond
      the boundaries of the wound. The exact etiology is still unknown and there is
      currently no appropriate treatment for keloid disease. METHODS: We analyzed
      sample tissues were obtained from 20 patients with keloid skin lesions and normal
      skin was obtained from 20 healthy donors. The telomeres were measured by Terminal
      Restriction Fragment (TRF) analysis and Real-Time PCR assay. Quantitative Real
      Time RT-PCR analysis of hTERT gene expression was performed and intracellular ROS
      generation was measured. RESULTS: In this study, we determined whether telomeric
      shortening and the expression of human telomerase reverse transcriptase (hTERT)
      occurs in keloid patients. Using Terminal Restriction Fragment (TRF) analysis and
      Real-Time PCR assay, we detected a significant telomere shortening of 30% in
      keloid specimens compared to normal skin. Using quantitative Real-Time RT-PCR,
      telomerase activity was found absent in the keloid tissues. Moreover, an increase
      in ROS generation was detected in fibroblasts cell cultures from keloid specimens
      as more time elapsed compared to fibroblasts from normal skin. CONCLUSION:
      Telomere shortening has been reported in several metabolic and cardiovascular
      diseases. We found that telomere shortening can also be associated with human
      keloids. Chronic oxidative stress plays a major role in the pathophysiology of
      several chronic inflammatory diseases. Here we found increased ROS generation in
      fibroblasts from keloid fibroblasts cell cultures when compared to normal skin
      fibroblasts. Hence we conclude that oxidative stress might be an important
      modulator of telomere loss in keloid because of the absence of active telomerase
      that counteracts telomere shortening.

PMID- 19863818
TI  - Penetrance of HNPCC-related cancers in a retrolective cohort of 12 large
      Newfoundland families carrying a MSH2 founder mutation: an evaluation using
      modified segregation models.
AB  - BACKGROUND: Accurate risk (penetrance) estimates for associated phenotypes in
      carriers of a major disease gene are important for genetic counselling of at-risk
      individuals. Population-specific estimates of penetrance are often needed as
      well. Families ascertained from high-risk disease clinics provide substantial
      data to estimate penetrance of a disease gene, but these estimates must be
      adjusted for possible specific sources of bias. METHODS: A cohort of 12
      independently ascertained HNPCC families harbouring a founder MSH2 mutation was
      identified from a cancer genetics clinic in St. John's, Newfoundland, Canada.
      Carrier status was known for 247 family members but phenotype information on up
      to 85 additional relatives with unknown carrier status was available; using
      modified segregation models these additional individuals could be included in the
      analyses. Three HNPCC-related phenotypes were evaluated as age at diagnosis of:
      any HNPCC cancer (first cancer), colorectal cancer (CRC), and endometrial cancer
      (EC) for females. RESULTS: Lifetime (age 70) risk estimates for male and female
      carriers were similar for developing any HNPCC cancer (Males = 98.2%, 95%
      Confidence Interval (CI) = (93.8%, 99.9%); Females = 92.8%, 95% CI = (82.4%,
      99.1%)) but female carriers experienced substantially reduced lifetime risk for
      developing CRC compared to male carriers (Females = 38.9%, 95% CI = (24.2%,
      62.1%); Males = 84.5%, 95% CI = (67.3%, 91.3%)). Female non-carriers had very low
      lifetime risk for these two outcomes while male non-carriers had lifetime risks
      intermediate to the female carriers and non-carriers. Female carriers had a
      lifetime risk of developing EC of 82.4%. Relative risks for developing any HNPCC
      cancer (carriers relative to non-carriers) were substantially greater for females
      compared to their male counterparts (Females = 54.8, 95%CI = (4.4, 379.8); Males
      = 9.7, 95% CI = (0.3, 23.8)). Relative risks for developing CRC at age 70 were
      substantially greater for females compared to their male counterparts (Females =
      23.7, 95%CI = (5.6, 137.9); Males = 6.8%, 95% CI = (2.3, 66.2)). However, the
      risk of developing CRC decreased with age among both genders. CONCLUSION: The
      proposed modified segregation-based models used to estimate age-specific risks
      for HNPCC phenotypes can reduce bias due to ascertainment and missing genotype
      information as well as provide estimates of absolute and relative risks.

PMID- 19863819
TI  - Robust algorithm for arrhythmia classification in ECG using extreme learning
      machine.
AB  - BACKGROUND: Recently, extensive studies have been carried out on arrhythmia
      classification algorithms using artificial intelligence pattern recognition
      methods such as neural network. To improve practicality, many studies have
      focused on learning speed and the accuracy of neural networks. However,
      algorithms based on neural networks still have some problems concerning practical
      application, such as slow learning speeds and unstable performance caused by
      local minima. METHODS: In this paper we propose a novel arrhythmia classification
      algorithm which has a fast learning speed and high accuracy, and uses Morphology
      Filtering, Principal Component Analysis and Extreme Learning Machine (ELM). The
      proposed algorithm can classify six beat types: normal beat, left bundle branch
      block, right bundle branch block, premature ventricular contraction, atrial
      premature beat, and paced beat. RESULTS: The experimental results of the entire
      MIT-BIH arrhythmia database demonstrate that the performances of the proposed
      algorithm are 98.00% in terms of average sensitivity, 97.95% in terms of average
      specificity, and 98.72% in terms of average accuracy. These accuracy levels are
      higher than or comparable with those of existing methods. We make a comparative
      study of algorithm using an ELM, back propagation neural network (BPNN), radial
      basis function network (RBFN), or support vector machine (SVM). Concerning the
      aspect of learning time, the proposed algorithm using ELM is about 290, 70, and 3
      times faster than an algorithm using a BPNN, RBFN, and SVM, respectively.
      CONCLUSION: The proposed algorithm shows effective accuracy performance with a
      short learning time. In addition we ascertained the robustness of the proposed
      algorithm by evaluating the entire MIT-BIH arrhythmia database.

PMID- 19863820
TI  - Staphylococcus aureus biofilm formation at the physiologic glucose concentration
      depends on the S. aureus lineage.
AB  - BACKGROUND: Since bacteria embedded in biofilms are far more difficult to
      eradicate than planktonic infections, it would be useful to know whether certain
      Staphylococcus aureus lineages are especially involved in strong biofilm
      formation. For this reason, in vitro biofilm formation of 228 clinical S. aureus
      isolates of distinct clonal lineages was investigated. RESULTS: At 0.1% glucose,
      more than 60% of the S. aureus strains associated with multilocus sequence typing
      (MLST) clonal complex (CC)8 produced large amounts of biomass, compared to 0-7%
      for various other clonal lineages. Additionally, S. aureus bloodstream isolates
      associated with MLST CC8 and CC7 had similar biofilm forming capacities as their
      commensal counterparts. Furthermore, strong biofilm formation could not be
      attributed to a specific accessory gene regulator (agr) genotype, as suggested
      previously. The agr genotypes were strictly associated with the clonal lineages.
      Moreover, strong biofilm formation was not related to slime formation. Congo red
      agar (CRA) screening is therefore not useful as a qualitative screening method
      for biofilm formation. CONCLUSION: The adherence to polystyrene surfaces under
      physiologic glucose concentration (0.1%) was dependent on the clonal lineage.
      Strains associated with MLST CC8 were markedly more often classified as strong
      biofilm former at glucose concentrations of 0%, 0.1% and 0.25%. The present study
      reveals that the MLST CC8 associated genetic background was a predisposing factor
      for strong biofilm formation in vitro, under all tested glucose concentrations.

PMID- 19863821
TI  - Application and evaluation of the MLVA typing assay for the Brucella abortus
      strains isolated in Korea.
AB  - BACKGROUND: A Brucella eradication program has been executed in Korea. To
      effectively prevent and control brucellosis, a molecular method for genetic
      identification and epidemiological trace-back must be established. As part of
      that, the MLVA typing assay was evaluated and applied to B. abortus isolates for
      analyzing the characteristics of the regional distribution and relationships of
      foreign isolates. RESULTS: A total of 177 isolates originating from 105 cattle
      farms for the period 1996 to 2008 were selected as representatives for the nine
      provinces of South Korea. A dendrogram of strain relatedness was constructed in
      accordance with the number of tandem repeat units for 17 loci so that it was
      possible to trace back in the restricted areas. Even in a farm contaminated by
      one source, however, the Brucella isolates showed an increase or decrease in one
      TRs copy number at some loci with high DI values. Moreover, those 17 loci was
      confirmed in stability via in-vitro and in-vivo passage, and found to be
      sufficiently stable markers that can readily identify the inoculated strain even
      if minor changes were detected. In the parsimony analysis with foreign Brucella
      isolates, domestic isolates were clustered distinctively, and located near the
      Central and Southern American isolates. CONCLUSION: The MLVA assay has enough
      discrimination power in the Brucella species level and can be utilized as a tool
      for the epidemiological trace-back of the B. abortus isolates. But it is
      important to consider that Brucella isolates may be capable of undergoing minor
      changes at some loci in the course of infection or in accordance with the changes
      of the host.

PMID- 19863822
TI  - Inferring within-patient HIV-1 evolutionary dynamics under anti-HIV therapy using
      serial virus samples with vSPA.
AB  - BACKGROUND: Analysis of within-patient HIV evolution under anti-HIV therapy is
      crucial to a better understanding the possible mechanisms of HIV drug-resistance
      acquisition. The high evolutionary rate of HIV allows us to trace its
      evolutionary process in real time by analyzing virus samples serially collected
      from the same patient. However, such studies are still uncommon due to the lack
      of powerful computational methods designed for serial virus samples. In this
      study, we develop a computational method, vSPA (viral Sequential Pathway
      Analysis), which groups viral sequences from the same sampling time into clusters
      and traces the evolution between clusters over sampling times. The method makes
      use of information of different sampling times and traces the evolution of
      important amino acid mutations. Second, a permutation test at the codon level is
      conducted to determine the threshold of the correlation coefficient for
      clustering viral quasispecies. We applied vSPA to four large data sets of HIV-1
      protease and reverse transcriptase genes serially collected from two AIDS
      patients undergoing anti-HIV therapy over several years. RESULTS: The results
      show that vSPA can trace within-patient HIV evolution by detecting many amino
      acid changes, including important drug-resistant mutations, and by classifying
      different viral quasispecies coexisting during different periods of the therapy.
      CONCLUSION: Given that many new anti-HIV drugs will be available in the near
      future, vSPA may be useful for quickly providing information on the acquisition
      of HIV drug-resistant mutations by monitoring the within-patient HIV evolution
      under anti-HIV therapy as a computational approach.

PMID- 19863823
TI  - Delay in tuberculosis case detection in Pwani region, Tanzania. A cross sectional
      study.
AB  - BACKGROUND: Delay in Tuberculosis (TB) case detection may worsen the disease and
      increase TB transmission. It is also a challenge to the National TB and Leprosy
      control Program (NTLP). METHODS: We conducted a cross sectional study in four out
      of six districts in Pwani region to estimate the extent and factors responsible
      for delay in TB case detection in Pwani region. Delays were divided into patient,
      health facility and total delay. RESULTS: We enrolled a total of 226 smear
      positive TB patients. Out of 226 patient's results were available for 206. The
      majority (66.5%) of the patients were males. Mean age for males and females were
      37.3 and 33.7 years respectively. Mean (SD) total delay was 125.5 (98.5) days
      (median 90). Out of 206 patients, 79 (38.35%) delayed to seek TB health care.
      Health facility delay was observed among 121 (58.7%) patients.Risk factors for
      delay was poor knowledge that chest pain may be a TB symptom (OR = 2.9; 95%CI
      1.20- 7.03) and the belief that TB is always associated with HIV/AIDS (OR = 2.7;
      95%CI 1.39-5.23). Risk for delay was low among patients who first presented to a
      government health facility (OR = 0.3; 95%CI 0.12- 0.71) and those presenting with
      chest pain (OR = 0.2; 95%CI 0.10-0.61). CONCLUSION: There is a considerable delay
      in TB case detection in Pwani mainly contributed by patients. Risk factors for
      delay include misconception about TB/HIV and poor knowledge of TB symptoms.

PMID- 19863824
TI  - Association of serum levels of lipid and its novel constituents with the
      different stages of esophageal carcinoma.
AB  - BACKGROUND: The aim of the study was to evaluate the association of
      immunoglobulin G type of autoantibodies to oxidized low-density lipoprotein
      (oxLDL-lgG) and oxLDL-lgM with the progression of esophageal squamous cell
      carcinoma (ESSC). METHODS: Residents from Feicheng, China aged 40 to 69 years
      were screened for esophageal lesions in a screening program conducted during the
      period of January 2008 to December 2006. There were 33 controls with normal
      esophageal squamous epithelium cells, 37 patients with basal cell hyperplasia, 47
      with esophageal squamous cell dysplasia, and 43 with ESCC. All the participants
      were diagnosed by biopsy and histopathological examination. Adiponectin, oxidized
      low-density lipoprotein (oxLDL), autoantibodies against oxLDL (oxLDL-ab), OxLDL
      lgG, and OxLDL-lgM were determined by enzyme linked immunosorbent assay (ELISA).
      Total cholesterol, High-density lipoprotein (HDL), triglyceride, serum albumin,
      and blood pressure were co-estimated. Analysis of covariance for lipid levels was
      used to control the influence of covariates. RESULTS: The level of oxLDL-lgM
      increased gradually along with esophageal carcinoma progression. The oxLDL-lgM
      levels in the ESCC group were the highest after possible covariates were
      controlled. Binary logistic regression showed that oxLDL-lgM had a positive
      correlation with the development of esophageal carcinoma, while oxLDL and oxLDL
      ab had a negative correlation with ESSC. No significant association between the
      levels of oxLDL-lgG and adiponectin and the different stages of ESSC was
      observed. CONCLUSION: The present study shows that the decreased oxLDL and oxLDL
      ab and the elevated oxLDL-lgM serum levels may relate to the development and
      progression of ESSC.

PMID- 19863825
TI  - An evidence-based approach to the diagnosis of ventilator-associated pneumonia.

PMID- 19863826
TI  - Technique and the rapid shallow breathing index.

PMID- 19863827
TI  - New dual ventilator modes: are we ready to perform large clinical trials?

PMID- 19863828
TI  - Comparison of semi-quantitative endotracheal aspirates to quantitative non
      bronchoscopic bronchoalveolar lavage in diagnosing ventilator-associated
      pneumonia.
AB  - BACKGROUND: Current strategies for diagnosing ventilator-associated pneumonia
      (VAP) favor the use of quantitative methods; however, semi-quantitative cultures
      of endotracheal aspirates are still commonly used. METHODS: The microbiological
      results of patients with suspected VAP who had both quantitative cultures with
      non-bronchoscopic bronchoalveolar lavage (BAL) and semi-quantitative cultures of
      endotracheal aspirate obtained within 24 hours of each other were retrospectively
      reviewed and compared, using a quantitative threshold of >or=10(4) colony-forming
      units/mL as a reference standard. RESULTS: 256 patients with paired cultures were
      identified. Concordance between endotracheal aspirate (any growth of pathogens)
      and non-bronchoscopic BAL was complete in 58.2% and completely discordant in
      23.8%. The sensitivity and specificity of endotracheal aspirate were 65.4% and
      56.1%, which improved to 81.2% and 61.9% when antibiotic management decisions
      were considered in the analysis. Twenty-six patients had endotracheal aspirate
      cultures that were falsely negative for pathogens, with 61.5% of these patients
      demonstrating growth of non-fermenting Gram-negative rods or methicillin
      resistant Staphylococcus aureus (MRSA) on non-bronchoscopic BAL. Overall, 45
      patients (17.5%) among the entire cohort had false positive endotracheal aspirate
      cultures, with 19 of these patients (42.2%) demonstrating growth of non
      fermenting Gram-negative rods or MRSA. CONCLUSIONS: Semi-quantitative cultures of
      endotracheal aspirate are poorly concordant with quantitative cultures obtained
      via non-bronchoscopic BAL. Although the performance of endotracheal aspirate
      improves when antibiotic treatment is considered, guiding therapy on the basis of
      semi-quantitative cultures may still result in failure to identify potentially
      multiple-drug-resistant pathogens, and would also tend to promote excessive
      antibiotic usage. Our data support the use of quantitative cultures in diagnosing
      VAP.

PMID- 19863829
TI  - Variation in the rapid shallow breathing index associated with common measurement
      techniques and conditions.
AB  - BACKGROUND: The rapid-shallow-breathing index (RSBI) is widely used to evaluate
      mechanically ventilated patients for weaning and extubation, but it is determined
      in different clinical centers in a variety of ways, under conditions that are not
      always comparable. We hypothesized that the value of RSBI may be significantly
      influenced by common variations in measurement conditions and technique. METHODS:
      Sixty patients eligible for a weaning evaluation after >or=72 hours of mechanical
      ventilation were studied over 15 months in a medical intensive care unit. RSBI
      was measured while the patients were on 2 different levels of ventilator support:
      5 cm H2O continuous positive airway pressure (CPAP) versus T-piece. RSBI was also
      calculated in 2 different ways: using the values of minute ventilation and
      respiratory rate provided by the digital output of the ventilator, versus values
      obtained manually with a Wright spirometer. Finally, RSBI was measured at 2
      different times of the day. RESULTS: RSBI was significantly less when measured on
      5 cm H2O CPAP, compared to T-piece: the medians and interquartile ranges were 71
      (52-88) breaths/min/L versus 90 (59-137) breaths/min/L, respectively (P<.001).
      There were no significant differences in the value of RSBI obtained using
      ventilator-derived versus manual measures of the breathing pattern. RSBI was also
      not significantly different in the morning versus evening measurements.
      CONCLUSIONS: RSBI can be significantly affected by the level of ventilator
      support, but is relatively unaffected by both the technique used to determine the
      breathing pattern and the time of day at which it is measured.

PMID- 19863830
TI  - Work of breathing in adaptive pressure control continuous mandatory ventilation.
AB  - BACKGROUND: Adaptive pressure control is a mode of mechanical ventilation where
      inflation pressure is adjusted by the ventilator to achieve a target tidal volume
      (VT). This means that as patient effort increases, inflation pressure is reduced,
      which may or may not be clinically appropriate. The purpose of this study was to
      evaluate the relationship between ventilator work output and patient effort in
      adaptive pressure control. METHODS: A lung simulator (ASL 5000) was set at
      compliance=0.025 L/cm H2O and resistance=10 cm H2O/L/s. Muscle pressure (Pmus)
      was a sine wave (20% inspiration, 5% hold, 20% release) that increased from 0-25
      cm H2O in steps of 5 cm H2O. The adaptive-pressure-control modes tested were:
      AutoFlow (Drager Evita XL), VC+ (Puritan Bennett 840), APV (Hamilton Galileo),
      and PRVC (Siemens Servo-i and Siemens Servo 300). The target VT was set at 320 mL
      (Pmus=15 cm H2O, inspiratory pressure=0 cm H2O) to allow delivery of a realistic
      VT as the simulated patient demanded more volume. All measurements were obtained
      from the simulator. RESULTS: Patient work of breathing (patient WOB) increased
      from 0 J/L to 1.88 J/L through the step increase in Pmus. Target VT was
      maintained as long as Pmus was below 10 cm H2O. VT then increased linearly with
      increased Pmus. The ventilators showed 3 patterns of behavior in response to an
      increase in Pmus: (1) ventilator WOB gradually decreased to 0 J/L as Pmus
      increased; (2) ventilator WOB decreased at the same rate as Pmus increased but
      plateaued at Pmus=10 cm H2O by delivering a minimum inspiratory pressure level of
      6 cm H2O; (3) ventilator WOB decreased as in patterns 1 and 2 to Pmus=10 cm H2O,
      but then decreased at a much slower rate. CONCLUSIONS: Adaptive-pressure-control
      algorithms differ between ventilators in their response to increasing patient
      effort. Notably, some ventilators allow the patient to assume all of the WOB, and
      some provide a minimum level of WOB regardless of patient effort.

PMID- 19863831
TI  - The addition of mechanical insufflation/exsufflation shortens airway-clearance
      sessions in neuromuscular patients with chest infection.
AB  - BACKGROUND: Mechanical insufflation/exsufflation (in-exsufflation) increases peak
      cough flow and may improve sputum clearance. No studies have compared current
      respiratory physiotherapy practice (manual percussion, shaking, and assisted
      cough) plus mechanical in-exsufflation to current physiotherapy practice without
      in-exsufflation in noninvasive-ventilation (NIV) dependent neuromuscular patients
      with an acute respiratory-tract infection. We hypothesized that airway clearance
      in these patients would be more effective with in-exsufflation, compared to
      without in-exsufflation. METHODS: Eight patients (6 male), median age 21.5 y
      (range 4-44 y). All had sputum retention, with an elevated C-reactive protein of
      113 mg/L (range 13-231 mg/L) and a white-cell count of 14x10(9) cells/L (range 7
      25x10(9) cells/L). Patients underwent a 2-day randomized crossover treatment
      program, with in-exsufflation for one session and without in-exsufflation for the
      second, with a reverse-crossover on the next day. Treatment time after 30 min (or
      earlier if sputum clearance was complete) was recorded. Outcome measures were
      heart rate, pulse oximetry (SpO2), transcutaneous carbon dioxide tension
      (PtcCO2), and independently assessed auscultation score. Patients rated
      effectiveness on a visual analog scale. RESULTS: Treatment time after 30 min was
      significantly shorter with in-exsufflation, versus without in-exsufflation
      session (30+0=30 min (range 0-26 min) vs 30+17=47 min (range 0-35 min) (P=.03).
      There was a significant improvement in auscultation score in both groups (with in
      exsufflation 2.9+/-1.9 to 1.8+/-2.0, P=.02; without in-exsufflation 3.4+/-2.0 to
      2.3+/-2.2, P=.007). Visual-analog-scale score for the amount of sputum cleared in
      both treatment groups showed a decline ( <.05). There was no difference in mean
      heart rate, SpO2, or PtcCO2 with either treatment. CONCLUSIONS: This is a short
      term study of the use of in-exsufflation as a supplement to standard NIV plus
      physiotherapy in a small group of patients with neuromuscular disease. The
      addition of mechanical in-exsufflation shortened airway-clearance sessions. The
      device appeared to be safe and well tolerated, and may provide additional benefit
      to patients with neuromuscular disease and upper-respiratory-tract infection;
      further studies are indicated.

PMID- 19863832
TI  - Laboratory evaluation of the Acapella device: pressure characteristics under
      different conditions, and a software tool to optimize its practical use.
AB  - BACKGROUND: The Acapella is a respiratory rehabilitation device designed to aid
      sputum clearance. When the patient exhales through this device, continuous and
      oscillatory pressure levels are produced. The adequate practical use of the
      Acapella is critically dependent on the characteristics of the produced pressure,
      which include the production of a mean pressure>or=10 cm H2O and a matching of
      the oscillation frequency with the respiratory-system resonance frequency, and/or
      with the frequency of ciliary movement (approximately 13 Hz). The development of
      a dedicated software tool would contribute to optimize the clinical application
      of this device. Thus, the aim of this study was 2-fold: to characterize the
      mechanical behavior of the Acapella, and to develop a software tool to ease the
      practical use of this device. METHODS: An experimental setup was assembled in
      order to study mean pressure, oscillation frequency, and the oscillation
      amplitudes produced by 3 Acapella devices (model green) in the whole range of
      instrument adjustments and under air flow rates ranging from 200 mL/s to 800
      mL/s. In order to increase flexibility, allowing the fast integration of further
      information obtained in future studies, the software was developed in a graphical
      environment. RESULTS: The device characterization showed an oscillation frequency
      varying from 8 Hz to 21 Hz, mean pressure ranging from 3 cm H2O to 23 cm H2O, and
      oscillation amplitude from 4 cm H2O to 9 cm H2O. These parameters increased with
      flow and instrument adjustment. A user-friendly software was developed,
      incorporating the current knowledge concerning secretion removal. After the
      introduction of the desired frequency and the patient air flow by the user, the
      software automatically calculates the necessary instrument adjustment, as well as
      mean pressure and oscillation amplitude. CONCLUSIONS: The Acapella device may
      produce clinically adequate values of mean pressure and oscillation frequency.
      However, it depends on its use at optimized conditions. The user-friendly
      software proposed in this study could help the user to achieve these conditions.

PMID- 19863833
TI  - The influence of breathing pattern during nebulization on the delivery of
      arformoterol using a breath simulator.
AB  - BACKGROUND: Patients with obstructive airway conditions, including chronic
      obstructive pulmonary disease (COPD), use nebulizers for drug delivery. Tidal
      breathing patterns employed by patients during nebulized drug delivery may vary.
      It is unclear whether different breathing patterns affect the emitted quantity of
      nebulized drug. This in vitro study evaluated whether different tidal breathing
      patterns that encompass a range that could be observed in COPD patients influence
      the emitted amount of nebulized arformoterol. METHODS: Breath-simulation
      experiments used a Pari LC Plus nebulizer in combination with the Duraneb 3000
      portable aerosol system. Four breathing patterns that could represent a range of
      tidal volumes and inspiratory and expiratory times observed in patients with COPD
      were studied. The amount of arformoterol on the inspiratory and expiratory
      filters, and the residual amount in the nebulizer bowl were determined via high
      pressure liquid chromatography. Results are expressed as a percent of the nominal
      dose (15 microg in 2 mL). RESULTS: The total amount of arformoterol on the
      inspiratory filter increased with a longer inspiratory phase of tidal breathing
      (ranging from 8.0% to 13.1%), while the expiratory filter dose remained similar
      (7.9% to 8.7%). The total emitted dose (expiratory and inspiratory amounts
      combined) for all patterns was 16.0% to 21.1% of the nominal dose. Retained
      arformoterol amount (not emitted) ranged from 55.9% to 62.3% of the nominal dose.
      CONCLUSIONS: These breath-simulation experiments suggest that only about 20% of
      the nominal 15-microg arformoterol dose was emitted from the nebulizer apparatus
      with each of the 4 tidal breathing patterns studied, and that a longer
      inspiratory phase was associated with greater inhaled dose.

PMID- 19863834
TI  - Varicose bronchiectasis and bronchopulmonary dysplasia.
AB  - As a result of improved therapies and technology, including the use of surfactant
      replacement, the features of bronchopulmonary dysplasia (BPD) have changed, and a
      "new BPD" is emerging that is substantially different from the classical form of
      the disease. As the pathogenesis of BPD is evolving, so are other features of the
      disorder, including radiologic features. We describe varicose bronchiectasis with
      a bulbous appearance in a 6-year-old child with a complicated course including
      BPD during the neonatal period.

PMID- 19863835
TI  - Refractory hypoxemic respiratory failure due to adenocarcinoma of the lung with
      predominant bronchioloalveolar carcinoma component.

PMID- 19863837
TI  - Don't use the flawed fixed ratio to diagnosis COPD.

PMID- 19863838
TI  - Trypanocidal drugs: mechanisms, resistance and new targets.
AB  - The protozoan parasites Trypanosoma brucei and Trypanosoma cruzi are the
      causative agents of African trypanosomiasis and Chagas disease, respectively.
      These are debilitating infections that exert a considerable health burden on some
      of the poorest people on the planet. Treatment of trypanosome infections is
      dependent on a small number of drugs that have limited efficacy and can cause
      severe side effects. Here, we review the properties of these drugs and describe
      new findings on their modes of action and the mechanisms by which resistance can
      arise. We further outline how a greater understanding of parasite biology is
      being exploited in the search for novel chemotherapeutic agents. This effort is
      being facilitated by new research networks that involve academic and
      biotechnology/pharmaceutical organisations, supported by public-private
      partnerships, and are bringing a new dynamism and purpose to the search for
      trypanocidal agents.

PMID- 19863839
TI  - Genetic modelling of childhood social development and personality in twins and
      siblings with schizophrenia.
AB  - BACKGROUND: Abnormalities in early social development and personality are present
      in patients with schizophrenia and their unaffected relatives. This study aimed
      to establish the degree to which these childhood and adolescent developmental
      abnormalities are genetically determined. METHOD: We used a combined twin and
      family study design (n=531) to assess childhood and adolescent social adjustment
      and schizotypal personality traits in 98 twin pairs (n=196) varying in their
      zygosity and concordance for schizophrenia and 156 sibling clusters (n=335)
      varying in their concordance for schizophrenia. RESULTS: Schizophrenia was
      significantly associated with childhood and adolescent deficits in social
      adjustment and personality, with additive genetic effects being the main source
      of these phenotypic correlations. CONCLUSIONS: Abnormalities of social adjustment
      and personality are present in children and adolescents who later develop
      schizophrenia, reflecting the influence of common genetic risk.

PMID- 19863840
TI  - Two plus two equals three? Do we need to rethink lifetime prevalence?

PMID- 19863841
TI  - Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer's
      disease.
AB  - BACKGROUND: Abnormal levels of biomarkers in cerebrospinal fluid (CSF) and
      atrophy of medial temporal lobe (MTL) structures on magnetic resonance imaging
      (MRI) are being used increasingly to diagnose early Alzheimer's disease (AD). We
      evaluated the claim that these biomarkers can detect preclinical AD before
      behavioural (i.e. memory) symptoms arise. METHOD: We included all relevant
      longitudinal studies of CSF and MRI biomarkers published between January 2003 and
      November 2008. Subjects were not demented at baseline but some declined to mild
      cognitive impairment (MCI) or to AD during follow-up. Measures of tau and beta
      amyloid in CSF, MTL atrophy on MRI, and performance on delayed memory tasks were
      extracted from the papers or obtained from the investigators. RESULTS: Twenty-one
      MRI studies and 14 CSF studies were retrieved. The effect sizes of total tau (t
      tau), phosphorylated tau (p-tau) and amyloid beta 42 (a beta 42) ranged from 0.91
      to 1.11. The effect size of MTL atrophy was 0.75. Memory performance had an
      effect size of 1.06. MTL atrophy and memory impairment tended to increase when
      assessed closer to the moment of diagnosis, whereas effect sizes of CSF
      biomarkers tended to increase when assessed longer before the diagnosis.
      CONCLUSIONS: Memory impairment is a more accurate predictor of early AD than
      atrophy of MTL on MRI, whereas CSF abnormalities and memory impairment are about
      equally predictive. Consequently, the CSF and MRI biomarkers are not very
      sensitive to preclinical AD. CSF markers remain promising, but studies with long
      follow-up periods in elderly subjects who are normal at baseline are needed to
      evaluate this promise.

PMID- 19863842
TI  - Trajectories of change in depression severity during treatment with
      antidepressants.
AB  - BACKGROUND: Response and remission defined by cut-off values on the last observed
      depression severity score are commonly used as outcome criteria in clinical
      trials, but ignore the time course of symptomatic change and may lead to
      inefficient analyses. We explore alternative categorization of outcome by
      naturally occurring trajectories of symptom change. METHOD: Growth mixture models
      were applied to repeated measurements of depression severity in 807 participants
      with major depression treated for 12 weeks with escitalopram or nortriptyline in
      the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent
      trajectory classes were validated as outcomes in drug efficacy comparison and
      pharmacogenetic analyses. RESULTS: The final two-piece growth mixture model
      categorized participants into a majority (75%) following a gradual improvement
      trajectory and the remainder following a trajectory with rapid initial
      improvement. The rapid improvement trajectory was over-represented among
      nortriptyline-treated participants and showed an antidepressant-specific pattern
      of pharmacogenetic associations. In contrast, conventional response and remission
      favoured escitalopram and produced chance results in pharmacogenetic analyses.
      Controlling for drop-out reduced drug differences on response and remission but
      did not affect latent trajectory results. CONCLUSIONS: Latent trajectory mixture
      models capture heterogeneity in the development of clinical response after the
      initiation of antidepressants and provide an outcome that is distinct from
      traditional endpoint measures. It differentiates between antidepressants with
      different modes of action and is robust against bias due to differential
      discontinuation.

PMID- 19863843
TI  - Role of oxytocin/oxytocin receptor system in regulation of cell growth and
      neoplastic processes.
AB  - Novel sites of oxytocin receptor expression have recently been detected in
      central nervous system, cardiomyocytes, endothelial cells, various carcinoma
      cells, etc. These and other discoveries have greatly expanded the classical
      biological roles of oxytocin, which are stimulation of uterine smooth muscle
      contraction at parturition and milk ejection during lactation. It is becoming
      clear that the great diversity of oxytocin actions in the brain and peripheral
      organs is paralleled by activation of a diversity of signalling pathways. On the
      other hand, until now only one single oxytocin receptor type has been detected.
      This receptor belongs to G protein-coupled receptors and in dependence on cell
      conditions it binds to different G proteins; this phenomenon is called receptor-G
      protein promiscuity. Thus, in the same cells oxytocin can activate multiple
      responses at the same time. Recently, the oxytocinergic system has also been
      implicated in the growth modulation of various neoplastic cells, where it may
      inhibit or stimulate cell proliferation in dependence on cell type and activated
      metabolic pathways. The discovery of novel oxytocin receptor-linked signalling
      cascades brings interesting knowledge opening new avenues for research in
      oncology and molecular pharmacology with perspectives of finding new therapeutic
      agents.

PMID- 19863844
TI  - BAFF from bone marrow-derived mesenchymal stromal cells of rheumatoid arthritis
      patients improves their B-cell viability-supporting properties.
AB  - Mesenchymal stromal cells (MSCs) represent a unique cell type with anti
      proliferative effects on activated T and B cells. Based on our observation of
      differences between rheumatoid arthritis and osteoarthritis bone marrow B cells
      we hypothesized that rheumatoid arthritis bone marrow MSCs may enhance B-cell
      survival. We aimed to compare the effect of rheumatoid arthritis and
      osteoarthritis bone marrow-derived MSCs (rheumatoid arthritis MSCs,
      osteoarthritis MSCs) on the survival of healthy donor purified B cells.
      Rheumatoid arthritis and osteoarthritis MSCs were isolated from patients
      undergoing hip replacement surgery, and cultured in vitro for 2-5 passages.
      Washed cells were co-cultured with CD20+ B cells for 30-90 hours. Cell survival
      was analysed using 7-amino-actinomycin D labelling by flow cytometry. Expression
      of mRNA and protein was determined by RT-PCR and flow cytomery. Co-culture with
      both rheumatoid arthritis MSCs and osteoarthritis MSCs significantly enhanced B
      cell survival, the effect being more prominent in rheumatoid arthritis MSCs. Both
      types of MSCs displayed expression of B cell-activating factor mRNA and protein.
      Blocking B cell-activating factor signalling from MSCs by specific anti-B cell
      activating factor and anti-B cell-activating factor receptor antibodies weakly
      reversed the effect of MSCs on B-cell survival mainly in rheumatoid arthritis
      MSCs. MSC interaction with B cells provides stimuli for B-cell survival and
      therefore may contribute to the pathogenesis of rheumatoid arthritis. MSC-derived
      factors other than B cell-activating factor are likely to contribute to this
      effect. This feature is more prominent in rheumatoid arthritis MSCs, possibly due
      to the B cell-activating factor.

PMID- 19863845
TI  - Metastases development following local tumour treatment.
AB  - Transplantable mouse methylcholanthrene- induced fibrosarcoma (CMC4 tumour
      growing in CBA/HZgr mice), characterized by lung metastases developing shortly
      after local tumour cell transplantation, was used as an experimental model to
      investigate the problem of tumour metastases after local tumour treatment.
      Surgery and/or irradiation were performed on locally growing tumour of particular
      size. Further, heavily irradiated, viable but not dividing tumour cells,
      imitating the situation in treated tumour-bearing organism, were injected
      intraperitoneally in a parallel group of treated tumour-bearing mice. The animals
      were killed 35 days after tumour transplantation and the number and volume of
      lung metastases were determined. Depending on the treatment performed, when the
      tumour mass was reduced or even eliminated, the number of lung metastases and
      their volume were significantly lower than in control mice, but the addition of
      tumour mass (injection of heavily irradiated tumour cells) resulted in a
      significant increase in lung metastases parameters, pointing to a possible role
      of the host's immune reaction against the tumour. Further, the release of a
      simple molecule, such as nitric oxide, from tumour mass seems to be detrimental
      for the survival of tumour cells and subsequently their metastases through the
      induction of angiogenesis and possible suppression of immune reaction. Thus,
      complex mechanisms could be involved when a locally growing tumour is exposed to
      a particular therapeutic approach.

PMID- 19863846
TI  - The influence of variations in the DNA repair (XRCC1) gene on HIV-1/AIDS among
      Indian population.
AB  - Genetic polymorphisms in DNA repair genes may influence individual variations in
      the DNA repair capacity. Polymorphisms in the XRCC1 gene that cause amino acid
      substitutions may impair the interaction of its proteins (XRCC1) with the other
      enzymatic proteins and consequently alter DNA repair function, which may be
      associated with the risk of HIV-1/AIDS disease. In this study, we aimed to
      determine the frequency of polymorphisms in XRCC1 codon 399 in a sample of Indian
      population with HIV-1/AIDS to evaluate its association with the disease.
      Polymerase chain reaction and restriction fragment length polymorphism were used
      to analyse XRCC1 Arg399Gln polymorphisms in 300 positively diagnosed cases with
      HIV-1/AIDS and an equal number of negatively diagnosed controls of the matched
      age. The XRCC1 homozygous variant genotype Gln399Gln was associated with an
      increased risk of HIV-1/AIDS disease (OR = 1.8, 95% CI 1.10-2.94), while no
      association was found with the Arg399Gln genotype. Polymorphisms in the XRCC1
      homozygous variant genotype for the 399Gln allele were associated with the risk
      of HIV-1/AIDS disease in a sample of North Indian population.

PMID- 19863847
TI  - Association of the eNOS 4a/b and -786T/C polymormphisms with coronary artery
      disease, obesity and diabetes mellitus.
AB  - The aim was to assess the relationship between eNOS 4a/b and -786T/C
      polymorphisms with coronary artery disease (CAD), obesity and diabetes mellitus.
      Total number of 1313 patients underwent coronary angiography, 939 had significant
      CAD (stenosis of > or = 1 coronary artery > or = 50%), 222 had smooth coronary
      arteries. Patients with insignificant atherosclerosis were excluded, the study
      finally comprised 1161 patients. The analysis of eNOS 4a/b and -786T/ C
      polymorphisms was performed by polymerase chain reaction. No significant
      interaction was found between -786T/C polymorphism and solitary CAD or CAD with
      diabetes and obesity. For 4a/b polymorphism, genotypes aa+ab were almost three
      times more frequent in diabetic patients without CAD versus patients without CAD
      and without diabetes--OR 2.79; P = 0.009, Pcorr = 0.03. In 4a/b polymorphism and
      CAD with obesity and diabetes: bb genotype was significantly more frequent: in
      patients with CAD, diabetes and obesity in comparison with obese diabetic
      patients without CAD (OR = 3.63, Pcorr = 0.05); in non-diabetic non-obese
      patients with CAD, versus diabetic and obese patients without CAD (OR = 3.38,
      Pcorr = 0.05); in obese non-diabetic patients without CAD vs. obese diabetic
      patients without CAD (OR = 5.91, Pcorr = 0.01); in patients without CAD, obesity
      and diabetes vs. obese diabetic patients without CAD (OR = 3.59, Pcorr = 0.05).
      The eNOS 4a/b polymorphism has significant association with diabetes mellitus in
      CAD-negative patients, and with CAD in combination with obesity and diabetes
      mellitus. No association between 4a/b or -786T/C polymorphism and solitary CAD
      was found.

PMID- 19863848
TI  - Polymorphisms in serotonin-related genes in anorexia nervosa. The first study in
      Czech population and metaanalyses with previously performed studies.
AB  - Anorexia nervosa is a serious psychiatric disorder characterized by the inability
      to maintain normal body weight. The frequently studied polymorphisms in the
      serotonin 5-HT2A receptor gene (-1438A/G) and in serotonin transporter 5-HTT gene
      (LPR, VNTR) have led to controversial results in different populations. The aim
      of the study was to address association of the above-mentioned polymorphisms with
      anorexia nervosa in the Czech population. We genotyped a well-defined group of 75
      patients with anorexia nervosa (average age of 25.39 years, SD 6.18; average BMI
      14.65 (SD 1.38)). The control group consisted of 65 Caucasian healthy females
      (average age 25.76 years, SD 5.12; average BMI 20.69, SD 1.85). The 5-HT2A
      receptor -1438A/G polymorphism analysis showed a trend for the association with
      odds ratios for risk allele A being in the same direction. In combination with a
      previously published Polish cohort, the allelic test reached a suggestive
      borderline (P = 0.0362, chi2 statistics, 1 df). In meta-analysis which included
      all published results for allelic tests, the resulting P value was highly
      significant (0.0003, chi2 statistics, 1 df). Using quantitative association of 5
      HTR2A polymorphism with BMI in the Czech sample, a borderline association (P =
      0.055) was observed. In 5-HTT, LPR polymorphism analysis, unlike in 5-HT2A,
      neither allelic nor quantitative association with BMI for the bi-allelic 5-HTT
      marker was observed. Results of this study support previous reports of a
      significant role of the A allele (-1438A/G, 5-HT2A receptor) as a risk factor in
      anorexia nervosa.

PMID- 19863849
TI  - Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan
      and sildenafil for pulmonary arterial hypertension within their licensed
      indications: a systematic review and economic evaluation.
AB  - OBJECTIVE(S): To investigate the clinical and cost-effectiveness of epoprostenol,
      iloprost, bosentan, sitaxentan and sildenafil for the treatment of adults with
      pulmonary arterial hypertension (PAH) within their licensed indications. DATA
      SOURCES: Major electronic databases (including the Cochrane Library, MEDLINE and
      EMBASE) were searched up to February 2007. Further data were obtained from
      dossiers submitted to NICE by the manufacturers of the technologies. REVIEW
      METHODS: The systematic clinical and economic reviews were conducted according to
      accepted procedures. Model-based economic evaluations of the cost-effectiveness
      of the technologies from the perspective of the UK NHS and personal social
      services were carried out. RESULTS: In total, 20 randomised controlled trials
      (RCTs) were included in this assessment, mostly of 12-18 weeks duration and
      comparing one of the technologies added to supportive treatment with supportive
      treatment alone. Four published economic evaluations were identified. None
      produced results generalisable to the NHS. There was no consensus in the industry
      submissions on the most appropriate model structure for the technology
      assessment. Improvement in 6-minute walk distance (6MWD) was seen with
      intravenous epoprostenol in primary pulmonary hypertension (PPH) patients with
      mixed functional class (FC) (mainly III and IV, licensed indication) compared
      with supportive care (58 metres; 95% CI 6-110). For bosentan compared with
      supportive care, the pooled result for improvement in 6MWD for FCIII patients
      with mixed PAH (licensed indication) was 59 metres (95% CI 20-99). For inhaled
      iloprost, sitaxentan and sildenafil no stratified data for improvement in 6MWD
      were available. The odds ratio (OR) for FC deterioration at 12 weeks was 0.40
      (95% CI 0.13-1.20) for intravenous epoprostenol compared with supportive care.
      The corresponding values for inhaled iloprost (FCIII PPH patients; licensed
      indication), bosentan, sitaxentan (FCIII patients with mixed PAH; licensed
      indication) and sildenafil (FCIII patients with mixed PAH; licensed indication)
      were 0.29 (95% CI 0.07-1.18), 0.21 (95% CI 0.03-1.76), 0.18 (95% CI 0.02-1.64)
      and [Commercial-in-confidence information has been removed] respectively. The
      incremental cost-effectiveness ratios (ICERs) for the technologies plus
      supportive care compared with supportive care alone, determined by independent
      economic evaluation, were 277,000 pounds/quality-adjusted life-year (QALY) for
      FCIII and 343,000 pounds/QALY for FCIV patients for epoprostenol, 101,000
      pounds/QALY for iloprost, 27,000 pounds/QALY for bosentan and 25,000 pounds/QALY
      for sitaxentan. For the most part sildenafil plus supportive care was more
      effective and less costly than supportive care alone and therefore dominated
      supportive care. In the case of epoprostenol the ICERs were sensitive to the
      price of epoprostenol and for bosentan and sitaxentan the ICERs were sensitive to
      running the model over a shorter time horizon and with a lower cost of
      epoprostenol. Two RCTs directly compared the technologies against each other with
      no significant differences observed between the technologies. Combinations of
      technologies were investigated in four RCTs, with some showing conflicting
      results. CONCLUSION(S): All five technologies when added to supportive treatment
      and used at licensed dose(s) were more effective than supportive treatment alone
      in RCTs that included patients of mixed FC and types of PAH. Current evidence
      does not allow adequate comparisons between the technologies nor for the use of
      combinations of the technologies. Independent economic evaluation suggests that
      bosentan, sitaxentan and sildenafil may be cost-effective by standard thresholds
      and that iloprost and epoprostenol may not. If confirmed, the use of the most
      cost-effective treatment would result in a reduction in costs for the NHS. Long
      term, double-blind RCTs of sufficient sample size that directly compare bosentan,
      sitaxentan and sildenafil, and evaluate outcomes including survival, quality of
      life, maintenance on treatment and impact on the use of resources for NHS and
      personal social services are needed.

PMID- 19863850
TI  - The challenges of iatrogenic proximal ureteric reconstruction.

PMID- 19863851
TI  - Low-risk prostate cancer and low testosterone: what are the acceptable
      alternatives?

PMID- 19863853
TI  - Management of fluid intake in patients with overactive bladder.
AB  - Overactive bladder (OAB) syndrome is a prevalent condition that affects millions
      of people worldwide. There is no curative treatment, and management is aimed at
      reducing symptoms and improving quality of life. Conservative treatment is first
      line therapy for OAB sufferers, including lifestyle interventions, bladder
      training, and pelvic floor exercises. The evidence for lifestyle interventions in
      the form of fluid manipulation, weight reduction, and smoking cessation is
      limited. However, these interventions are cheap and simple and have health
      benefits. Until recently, the advice regarding fluid manipulation, in terms of
      volume and type, has been controversial. Increasing evidence suggests that
      reducing fluid intake can improve OAB symptoms, with a general consensus that
      caffeine reduction may be beneficial. Further clinical trials are needed on fluid
      manipulation in terms of the types of fluids drank, the timing of fluid intake,
      and the effects of exercise and outside ambient temperature on OAB symptoms.

PMID- 19863852
TI  - Female voiding dysfunction: prevalence and common associations.
AB  - The understanding of voiding dysfunction has been greatly assisted by the current
      introduction of clear definitions for its diagnosis and for the abnormalities of
      urine flow rates and postvoid residuals that are its basis. Its prevalence in
      women with symptoms of pelvic floor dysfunction is up to 40%. Most of the recent
      research has centered on the associations of voiding dysfunction with age, pelvic
      organ prolapse, and prior continence surgery. The effects of parity, medications,
      and pelvic tumors have also been explored.

PMID- 19863854
TI  - The association between overactive bladder and diuretic use in the elderly.
AB  - Several recent population-based studies have provided insight into the clinical
      importance and impact of overactive bladder (OAB). Although OAB can affect anyone
      at any age, the prevalence tends to increase with advancing age. Diuretic use is
      also common among older adults, as the prevalence of clinical conditions such as
      hypertension and heart failure requiring its use increases markedly with age. By
      causing increased formation of urine by the kidneys, diuretics increase urinary
      frequency and may cause urinary urgency and incontinence. This review provides a
      summary of available data, focusing on the association between OAB and diuretic
      use in the elderly. Although there is very little research work in this area,
      available studies have provided insight into the possible contribution of
      diuretic use to OAB in the elderly. Based on a recent report, OAB symptoms are
      common among older adults using diuretics, particularly the loop-type, and are
      associated with poor quality of life. More studies are required to fully
      understand the association between diuretic use and OAB, particularly its impact
      on health-related quality of life.

PMID- 19863855
TI  - The relationship between sexual abuse and interstitial cystitis/painful bladder
      syndrome.
AB  - Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic syndrome
      characterized by irritative voiding symptoms and pelvic pain or discomfort.
      IC/PBS represents localized bladder pathophysiologic changes and central nervous
      system upregulation. Patients exhibit bladder hyperalgesia and allodynia.
      Childhood sexual abuse occurs in up to 27% of females in the United States.
      Adults with a prior history of abuse or traumatization demonstrate hypothalamic
      pituitary-adrenal (HPA) axis abnormalities, similar to IC/PBS patients. Childhood
      sexual abuse and physical traumatization are associated with subsequent lifelong
      risks of chronic pain syndromes. IC/PBS patients have increased rates of sexual
      abuse or physical traumatization histories compared with controls. IC/PBS
      patients with abuse histories tend to have greater pain intensity and lesser
      irritative voiding symptoms compared with nonabused IC/PBS patients. This article
      reviews the relationship between sexual abuse, HPA axis abnormalities, IC/PBS
      pathophysiology, and the role of sexual abuse on subsequent IC/PBS.

PMID- 19863856
TI  - The relationship between sleep apnea and overactive bladder.
AB  - Approximately 4% to 5% of middle-aged men are affected by obstructive sleep apnea
      (OSA) syndrome, which is known to cause urologic disorders, cardiovascular
      diseases, and an increased risk of stroke. The correlation between OSA, erectile
      dysfunction, and nocturia is well known; a recent study demonstrated the
      association between overactive bladder and urgency incontinence. This article
      discusses the current literature and therapeutic options, as well as our own
      experiences and consequences for affected patients.

PMID- 19863857
TI  - Testosterone therapy and prostate carcinoma.
AB  - Hypogonadism is a clinical and biochemical syndrome associated with a range of
      disease states that has significant effects on morbidity and mortality and also
      affects quality of life. Because of the increase in life expectancy and prostate
      carcinoma (PCa) survival, a significant increase in the number of men with
      hypogonadism who have undergone presumably curative treatment of PCa is
      anticipated. Despite the widespread belief regarding contraindication of
      testosterone administration to men with known or suspected PCa, there is no
      convincing evidence that the normalization of testosterone serum levels in men
      with low levels presents a deleterious effect on the evolution of the disease. In
      the few available case series describing testosterone replacement therapy (TRT)
      after treatment of PCa, no case of clinical or biochemical progression was
      observed. The available data suggest that TRT can be cautiously considered in
      selected hypogonadal men previously treated for curative intent of low-risk PCa
      and without evidence of active disease.

PMID- 19863858
TI  - Peyronie's surgery: graft choices and outcomes.
AB  - Peyronie's disease (PD), a localized fibrosis of the tunica albuginea surrounding
      the penile corpora, results in penile curvature and sexual dysfunction. Men with
      significant penile curvature and satisfactory erectile function are often treated
      with plaque incision or excision and grafting. The advantages and disadvantages
      of various grafting materials have long been debated. Graft materials can be
      divided into three categories: autologous tissue harvested from the patient's
      body, allograft or xenograft from another person or species, and synthetic
      grafts. Despite groundbreaking advances in physiology, synthetic materials, and
      tissue engineering, the ideal graft material has yet to be established. This
      review presents and discusses the variety of graft materials available for the
      surgical correction of PD. For this purpose, a MEDLINE search was conducted on PD
      until May 2009.

PMID- 19863859
TI  - Penile shortening after radical prostatectomy and Peyronie's surgery.
AB  - Penile shortening following radical prostatectomy and straightening procedures
      for Peyronie's disease can be a devastating and unwelcome side effect of these
      operations. The majority of men undergoing radical prostatectomy for prostate
      cancer have a measured loss of penile length, which also can occur in men with
      Peyronie's disease and may be exacerbated by surgery. Recent studies have
      investigated the mechanisms resulting in penile shortening, and various
      treatments have emerged to prevent and treat postoperative penile shortening.
      This article reviews the recent literature on penile length loss after radical
      prostatectomy and following correction of penile deformity for Peyronie's
      disease.

PMID- 19863860
TI  - Phalloplasty and penile implant surgery.
AB  - Impotence is often accompanied by loss of phallic length. To enhance penile
      prosthesis surgery, it is possible to perform simple adjuvant procedures that
      will increase perceived or true length. This article presents an overview of
      these techniques, which may be categorized as involving removal or fixation of
      tissue above or below the shaft of the penis; division of the suspensory
      ligament; and augmentation of the corpora cavernosa through stretch or grafting.
      We believe that the use of these techniques will become increasingly commonplace
      as patient satisfaction is reported.

PMID- 19863861
TI  - Treatment of erectile dysfunction following spinal cord injury.
AB  - Spinal cord injury (SCI) has a significant impact on erectile dysfunction.
      Treatment modalities for individuals with SCI are similar to treatments for those
      without SCI. Some of the most common methods of management include penile
      implants, oral phosphodiesterase (PDE) inhibitors, vacuum devices, intraurethral
      prostaglandins, and intracavernous injections. In addition to the advantages and
      disadvantages of these various modalities for able-bodied men, there are special
      considerations for men with SCI. Penile implants may help to keep an external
      condom catheter in place and provide more penile stability for intermittent
      catheterization. However, they have an increased risk of infection. Semirigid
      rods have an increased risk of erosion. Although convenient to use, PDE
      inhibitors are usually not effective in lower motor injuries. The hypotensive
      effects of intraurethral prostaglandins and PDE inhibitors need to be considered
      in SCI men with injuries at or above T6. Intracavernous injections are very
      effective; however, men with SCI require much lower doses than able-bodied men.

PMID- 19863862
TI  - Blood pressure-lowering drugs in preventing cardiovascular disease.

PMID- 19863863
TI  - AURORA and JUPITER trials: recognizing the limitations and expanding the benefits
      of statin treatment.

PMID- 19863864
TI  - Characterization and treatment of resistant hypertension.
AB  - Resistant hypertension is a common medical problem. It carries a significantly
      increased risk of end-organ damage and cardiovascular events compared with more
      easily controlled hypertension. Resistant hypertension is most often related to
      isolated systolic hypertension and is characterized by aldosterone excess and
      increased intravascular volume. Its diagnosis requires the exclusion of
      pseudoresistance. The etiology of resistant hypertension is almost always
      multifactorial. Common reversible contributing factors need to be identified and
      addressed. Secondary causes of hypertension, such as primary aldosteronism,
      parenchymal and vascular kidney disease, and obstructive sleep apnea, require
      investigation and effective treatment if present. Therapy for resistant
      hypertension should be based on use of rational drug class combinations at
      optimal doses, with particular attention to adequate diuretic use. The addition
      of an aldosterone antagonist may further improve blood pressure control.

PMID- 19863865
TI  - Role of ambulatory and home blood pressure recording in clinical practice.
AB  - Because of shortcomings of the office blood pressure (BP) measurement in
      individuals with hypertension (eg, white coat and masked hypertension effects,
      terminal digit bias, and large variability in BP among a small number of
      readings), use of out-of-office blood pressure measurements has become more
      common in clinical practice. The presence of the syndromes of white-coat and
      masked hypertension creates the concern that the office BP measurements are not
      reflective of an individual patient's true BP values. Home (or self) and
      ambulatory BP assessments have been used in numerous types of clinical trials and
      have demonstrated their usefulness as reliable research and clinical tools. In
      this article, we review the recent literature on the benefits and limitations of
      home (self) and ambulatory monitoring of the BP in clinical practice. In
      particular, how it relates to the diagnosis of patients with various
      presentations of hypertension and to cardio-vascular outcomes with long-term
      follow-ups of population cohorts.

PMID- 19863866
TI  - Hypertension and diastolic heart failure.
AB  - In patients with hypertension, pressure overload leads to left ventricular
      hypertrophy (LVH), myocardial fibrosis, and impaired diastolic filling without
      systolic dysfunction. Presently, diastolic heart failure accounts for about 50%
      of the heart failure population. Fatigue, dyspnea, reduced exercise tolerance,
      and peripheral edema are common presenting complaints. As a group, patients with
      diastolic heart failure are older and predominantly female. Diuretics are
      effective for treating congestive symptoms. beta Blockers and heart rate-lowering
      calcium blockers show benefit in smaller studies but have not been evaluated in
      definitive clinical trials. Renin-angiotensin-aldosterone system blockers reduce
      blood pressure, LVH, and myocardial fibrosis; however, long-term studies with
      angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
      demonstrate little effect on symptoms or survival, and inconsistent effects on
      heart failure hospitalization. At present, evidence-based treatment includes
      antihypertensive therapy to reduce progression from hypertension to heart
      failure. In patients with established heart failure, diuretics and other empiric
      treatments are used to control symptoms.

PMID- 19863867
TI  - Hypertension and atrial fibrillation.
AB  - Atrial fibrillation (AF) is an emerging public health problem. The most important
      risk factor for developing chronic AF is uncontrolled hypertension. Uncontrolled
      hypertension promotes the initiation and perpetuation of AF through atrial
      remodeling. Experimental evidence has demonstrated the important role of the
      renin-angiotensin system in atrial remodeling. Retrospective analysis of several
      large clinical trials and small prospective trials suggests the beneficial role
      of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in
      preventing the onset and recurrence of AF in different populations. Several large
      prospective trials with longer follow-up periods are in progress. These trials
      may provide definitive evidence for the use of these agents in the prevention of
      AF.

PMID- 19863868
TI  - The current state of RAAS blockade in the treatment of hypertension and
      proteinuria.
AB  - Hypertension is a well-established risk factor for cardiovascular disease (CVD)
      and chronic kidney disease (CKD). Patients with CKD have significant morbidity
      (ie, increased risk of CVD) and progression to end-stage renal disease. Increase
      in albuminuria over time to levels greater than 300 mg/d, in spite of blood
      pressure being at goal, is an independent predictor for nephropathy progression.
      Data provide support, however, for reducing proteinuria by at least 30% after
      treatment is initiated in patients with proteinuria. Pharmacologic blockade of
      the renin-angiotensin-aldosterone system (RAAS) slows progression of advanced
      proteinuric CKD more effectively than other antihypertensive agents. In post hoc
      analyses, this slowed progression has been correlated to reductions in
      proteinuria of 30% or more after blood pressure-lowering therapy is initiated.
      Increases in proteinuria, in spite of blood pressure reduction, are associated
      with faster declines in kidney function regardless of whether RAAS blockers are
      used.

PMID- 19863869
TI  - Secretory phospholipase A2: a multifaceted family of proatherogenic enzymes.
AB  - Secretory phospholipase A(2) (sPLA(2)) represents a class of enzymes that
      hydrolyze phospholipids from cellular membranes and lipoproteins, resulting in
      multifarious proatherogenic actions in the vessel wall. Proatherogenic actions of
      sPLA(2) involve lipoprotein remodeling that facilitates proteoglycan binding and
      formation of lipid aggregates that are rapidly internalized by tissue
      macrophages. The hydrolysis of phospholipids on cell membranes generates
      bioactive lipids and lipolipoproteins with increased oxidative susceptibility.
      These particles and other bioactive lipids activate inflammatory pathways in
      various cells of the vessel wall. Transgenic mice overexpressing groups IIA, V,
      and X have increased atherosclerosis formation, whereas mice deficient in these
      sPLA(2) isoenzymes have less atherosclerosis formation. In apolipoprotein E
      knockout mice fed an atherosclerotic diet, sPLA(2) inhibition with varespladib
      reduced atherosclerosis formation. The potential for sPLA(2) inhibitors for
      preventing cardiovascular events is being investigated.

PMID- 19863870
TI  - Emerging inflammatory markers for assessing coronary heart disease risk.
AB  - Although assessment of traditional coronary heart disease risk factors can often
      stratify individuals into low- or high-risk categories, additional means are
      needed to more precisely classify people clinically defined as intermediate-risk,
      to guide the intensity of risk-reducing therapies. The recognition that
      inflammatory pathways are important in the progression of atherosclerosis and its
      complications has prompted investigation to identify circulating risk markers
      that may be useful in risk stratification. This article summarizes recent studies
      on the current use of an emerging group of inflammatory markers: soluble CD-40
      ligand, interleukin-18, myeloperoxidase, B-type natriuretic peptides, secretory
      phospholipase A(2), lipoprotein-associated phospholipase A(2), and C-reactive
      protein. The demonstration that lowering C-reactive protein along with low
      density lipoprotein cholesterol with statins reduces events beyond cholesterol
      lowering alone suggests that titration of therapies using other emerging
      inflammatory markers may further reduce the toll of atherosclerosis in adult
      populations.

PMID- 19863871
TI  - Impaired fasting glucose as a treatment target in diabetes management.
AB  - Impaired fasting glucose (IFG) contributes to microvascular and macrovascular
      complications and increased cardiovascular disease risk. Although type 2 diabetes
      is largely considered to occur as a result of IFG, understanding of physiologic
      and associated management targets is uniformly lacking among health care
      professionals. Once definitions are standardized, diagnostic criteria and
      screening tools may help to identify individuals at risk sooner, thereby
      minimizing the rapid deterioration that often results. To counter the rising
      pandemic of obesity and diabetes, it is important to understand the vascular risk
      of IFG and impaired glucose tolerance in patients at risk.

PMID- 19863872
TI  - Low-density lipoprotein and apolipoprotein B: clinical use in patients with
      coronary heart disease.
AB  - Managing low-density lipoprotein (LDL) is an integral part of clinical practice.
      What remains controversial is whether we are using the best measure of LDL
      quantity for this purpose. Historically, the cholesterol content of LDL particles
      (LDLC) has been used to express LDL quantity. However, because of variability in
      the cholesterol carried in LDL particles, frequent disagreement occurs between
      LDLC and particle measures of LDL quantity, including apolipoprotein B-100 (apo
      B) or nuclear magnetic resonance (NMR) LDL particle number (LDL-P). Studies
      consistently demonstrate apo B and LDL-P are superior predictors of coronary
      heart disease (CHD) risk and superior indicators of low CHD risk on lipid
      lowering therapy. Recent recommendations advocate that, in addition to LDLC and
      non-high-density lipoprotein cholesterol, apo B (or NMR LDL-P) be used as a
      target of therapy. This article reviews the rationale supporting these
      recommendations and provides a model for integrating LDL particle measures in
      clinical practice.

PMID- 19863874
TI  - Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal
      allografts; clinical course and outcome.
AB  - BACKGROUND: Acute interstitial nephritis (AIN) secondary to trimethoprim
      sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure
      in native kidneys. TMP-SMX is the standard prophylactic agent against
      pneumocystis carinii (PCP) used in the early post-transplant period, however, it
      has to date only been indirectly associated with AIN in renal allografts. DESIGN,
      SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant
      patients with acute allograft dysfunction in whom a transplant biopsy
      demonstrated primary histopathologic features of allergic AIN, all of whom were
      receiving TMP-SMX in addition to other medications known to cause AIN. RESULTS:
      All cases occurred within 1 month of transplantation and accounted for 2.12%
      (11/518) of the total number of transplant biopsies performed during the study
      period. However, this figure increased to 10.1% (11/109) when those biopsies
      performed for early allograft dysfunction (< 1 month) were taken into account.
      After discontinuation of TMP- SMX alone, all patients had an immediate
      improvement in serum creatinine with excellent long term allograft function -
      mean improvement of serum creatinine from 465 micromol/l to 136 micromol/l at
      last follow-up (range 15 - 55 months). CONCLUSIONS: AIN secondary to TMP-SMX,
      although an uncommon cause of allograft dysfunction over the study period,
      accounted for over 10% of cases of allograft dysfunction within the first month
      of transplantation. Therefore, a high degree of clinical suspicion for TMP-SMX
      induced AIN is warranted when confronted with early acute allograft dysfunction.

PMID- 19863873
TI  - Improving risk factor modification: a global approach.
AB  - Despite recent advances in treating cardiovascular disease, many of the
      predisposing risk factors for heart disease are increasing in prevalence, raising
      concern that heart disease rates may rise in the years to come. When faced with
      the range of risk factors such as obesity, smoking, hypertension, hyperlipidemia,
      and diabetes, the clinician needs to address all components. After assessing an
      individual patient's global risk, the clinician should use a comprehensive risk
      modifying strategy that incorporates therapeutic lifestyle changes and
      pharmacologic therapy. Key elements of lifestyle changes are individualized
      treatment plans and frequent follow-up, whereas approaches to improve medical
      therapy include using structured programs to increase awareness and
      implementation of risk-reducing medications. Improving risk factor modification
      requires a global approach, not only in addressing the spectrum of risk factors,
      but also in using the full range of strategies available to clinicians.

PMID- 19863875
TI  - Glomerular filtration rate measurements by 125I-iothalamate should be corrected
      for inaccurate urine collections with 131I-hippuran.
AB  - BACKGROUND: Measuring GFR using exogenous markers without a bladder catheter,
      errors can be easily made due to incomplete urine collection. The aim was to
      quantify agreement for 125I-iothalamate GFR measurements with and without a
      correction for inaccurate urine collection using 131I-hippuran. METHODS: The last
      available GFR measurement of adult patients was included. GFR was measured in two
      subsequent clearance periods with 125I-iothalamate by the standard method with
      correction for inaccurate urine collections using 131I-hippuran. The uncorrected
      and corrected GFR measurements were compared within and between the time periods
      for each individual patient. To study the agreement between both methods,
      intraclass correlation coefficients (ICC) were calculated and Bland-Altman plots,
      with accompanying accuracies and precisions, were used. Cohen's kappa was
      calculated to analyze the agreement of both methods for classifying patients
      according to the stages of chronic kidney disease (CKD). RESULTS: For the 332
      stable included patients, the mean GFR of the uncorrected measurements was 77.8
      ml/min (34.7) and the mean GFR of the corrected measurements was 81.0 ml/min
      (34.9). The ICC was 0.80 for the uncorrected measurements with an accuracy of 7.3
      ml/min and a precision of 21.7 ml/min. For the corrected GFR measurements the ICC
      was 0.98, with an accuracy of 2.1 ml/min and a precision of 6.5 ml/min.
      Comparison between the methods showed an ICC of 0.95, an accuracy of 3.2 and a
      precision of 11.0. In total, 86% of the patients were classified similarly into
      CKD stages with both methods, overall Cohen's kappa was 0.81. CONCLUSION:
      Agreement was better for GFR measurements corrected for inaccurate urine
      collections. Therefore, GFR measurements with 125I-iothalamate should be
      corrected for inaccurate urine collections using 131I-hippuran. Without such
      correction the GFR is easily underestimated which may lead to overtreatment.

PMID- 19863876
TI  - Differential effects of short-term growth hormone therapy on the cardiovascular
      risk profile in patients with chronic kidney disease: a pilot study.
AB  - Chronic kidney disease (CKD) is highly associated with an increased
      cardiovascular morbidity and mortality and is also a state of growth hormone (GH)
      resistance. We examined the impact of a short-term treatment with rhGH on
      circulating markers of cardiovascular risk in nonmalnourished CKD patients in a
      single-center, nonrandomized pilot study. Patients with stable CKD Stage 3 - 5
      and age- and sex-matched healthy controls (n = 15 each) received a 7-day
      treatment with rhGH (1.33 mg/m2 body surface area per day, approximately 30
      microg/kg). Prior to onset of rhGH therapy, at the end of the treatment period
      and at the end of a 7-day wash-out period blood was drawn to assess changes in
      circulating markers of cardiovascular risk. At time of enrollment CKD patients
      showed elevated serum concentrations of phosphate, calcium x phosphate product,
      PTH, fibroblast growth factor-23 (FGF-23), triglycerides, leptin and homocysteine
      compared to controls. In patients and controls rhGH treatment induced an increase
      in circulating insulin-like growth factor I (IGF-I), and the molar ratio of IGF
      I/IGF binding protein 3 as well as an elevation of glucose, insulin, and
      triglycerides, whereas serum urea was decreased. In CKD patients, rhGH treatment
      raised concentrations of leptin, whereas LDL-cholesterol, homocysteine,
      phosphate, and 25-hydroxyvitamin D were significantly reduced. In controls, but
      not in CKD patients, rhGH raised 1,25-dihydroxy-vitamin D3 serum levels, which
      were even more elevated at the end of the wash-out period. In conclusion, short
      term treatment with rhGH in CKD patients affects not only insulin and glucose
      metabolism but also affects serum lipid profile, i.e., LDL-cholesterol, leptin
      and homocysteine. Long-term trials are required to evaluate the impact of rhGH on
      cardiovascular morbidity and mortality.

PMID- 19863878
TI  - IgG nephropathy - confusion and overlap with C1q nephropathy.
AB  - BACKGROUND: IgG nephropathy is one of the most recently described
      glomerulopathies, which frequently overlaps with C1q nephropathy. To clarify this
      entity, we evaluated renal biopsy cases with IgG deposits as a sole or
      predominant immunoglobulin. METHODS: Fourteen cases demonstrating IgG as a
      predominantly deposited immunoglobulin in patients without infectious or
      autoimmune diseases between 1997 and 2008 were studied. Twelve patients had
      glomerular disease in the native kidney and the other 2 were renal allograft
      recipients. RESULTS: Clinical presentation was microscopic hematuria,
      proteinuria, or both and nephrotic syndrome was observed in 3 patients. Segmental
      glomerulosclerosis was observed in 4 patients and mesangial hypercellularity was
      present in 7. Tubulointerstitial changes were not evident except for allograft
      biopsies. On immunofluorescence, mesangial or capillary wall IgG deposits were
      present in all cases, and C1q was observed in 11 cases in a similar pattern with
      IgG, co-dominant in 5 cases and dominant in 1. CONCLUSIONS: Since a significant
      overlap is frequently observed in these two rare conditions, we suggest a
      tentative diagnosis of IgG/C1q nephropathy in such cases.

PMID- 19863877
TI  - Prognostic relevance of clinical and histological features in IgA nephropathy
      treated with steroid and angiotensin receptor blockers.
AB  - BACKGROUND: The prognostic relevance of clinical and histological features on
      renal outcome has not been assessed in patients with IgA nephropathy (IgAN)
      treated with the combination therapy of steroid and angiotensin receptor blockers
      (ARB). METHODS: A prospective trial of a combination of steroid and ARB was
      performed in 50 patients with IgAN, proteinuria and serum creatinine levels < 2
      mg/dl. RESULTS: Over a mean follow-up period of 4 years, the combination therapy
      reduced proteinuria and hematuria and improved renal function in most patients.
      The mean change in estimated GFR (eGFR) was + 0.30 +/- 0.74 ml/min/1.73 m2/month.
      Forty-three patients (86%) exhibited stable renal function and 7 patients (14%)
      reached the primary end point of a (3) 20% decrease in eGFR from baseline levels.
      Between the nonprogressive and progressive patients, there were significant
      differences in the levels of urine protein/ creatinine excretion ratio (PCR) at
      baseline and throughout the follow-up period as well as baseline eGFR and degree
      of glomerular crescents (p < 0.05). Forty (80%) and 24 patients (48%) had a urine
      PCR < 1 and < 0.3 g/g, respectively, at their last follow-up. Renal survival was
      better in patients who had initial urine PCR < 3 g/g as well as final PCR < 1
      g/g. Regression analysis revealed that the final urine PCR and age were critical
      determinants of slope of the eGFR by both univariate and multivariate analyses.
      However, eGFR, pathologic findings, systolic BP, proteinuria, and body mass index
      at the initial presentation were not predictive of slope. CONCLUSION: Our results
      indicate that achieving a low urinary protein excretion is the main determinant
      for the good outcome in patients treated with combination therapy.

PMID- 19863879
TI  - Optimal blood pressure control versus additional immunosuppressive therapy in
      idiopathic membranous nephropathy - a retrospective analysis.
AB  - The treatment of idiopathic membranous nephropathy (MN) with nephrotic syndrome
      comprises immunosuppressive therapy and antihypertensive treatment with the
      blockade of the renin-angiotensin system (RAS). Given the relatively benign
      natural history of MN, an immunosuppressive-free therapeutic regimen should be
      considered as the primary treatment option. In a single-center, retrospective
      analysis we compared the outcome of 54 patients with biopsy-proven idiopathic MN
      12, 24 and 60 months after initiation of therapy. All patients had RAS-blocking
      agents and 36 patients received additionally an immunosuppressive regimen. In
      both groups the patients initially had a nephrotic proteinuria (median 8.7 vs.
      6.0 g/day, n.s.). Median blood pressure reduction was comparable after 12, 24 and
      60 months in both groups. The median evolution of proteinuria during therapy
      after 12, 24 and 60 months was 3.4, 1.7 and 1.1 g/day in the group with
      immunosuppression compared to 3.0, 1.1 and 0.32 g/day in the non
      immunosuppressive group. After 60 months no patient developed endstage renal
      failure. The number of severe side effects was significantly higher in patients
      with immunosuppression. Regarding renal function and reduction of proteinuria,
      patients with idiopathic MN treated without immunosuppressive therapy but with
      measures to ensure optimal blood pressure control and the full blockade of RAS
      had a similar outcome after 60 months as compared to patients who received
      additional immunosuppressive therapy.

PMID- 19863880
TI  - Prospective studies on applications of a two-cuff Swan neck catheter and a
      Tenckhoff catheter to Chinese CAPD patients.
AB  - AIM: To compare the difference of clinical curative effects of continuous
      ambulant peritoneal dialysis (CAPD) patients in China by using a two-cuff Swan
      neck catheter and a Tenckhoff catheter. METHODS: 110 patients with end-stage
      renal disease (ESRD) were enrolled. They were divided into Group A (Swan neck
      catheter group, n = 55) and Group B (Tenckhoff catheter group, n = 55). One-year
      follow-up visits were made and information was recorded. Survival analysis was
      made by adopting the Kaplan-Meier method. RESULTS: After 12 month follow-up
      visits, 17 patients had died, 3 had been transferred to renal transplantation, 8
      had been transferred to hemodialysis, 3 were transferred to other hospitals, and
      the remaining 79 patients (71.8%) continued their peritoneal dialysis therapy in
      our hospital. 26 patients in both groups had peritonitis, with a total of 35
      occurrences taking place. The total incidence of peritonitis was 0.32
      times/patient year, with the detailed figure of 0.35 times/patient year for Group
      A and 0.29 times/patient year for Group B respectively (p > 0.05). Regarding
      mechanical complications of the 2 groups concerned, including catheter tip
      migration, Omental enwrapment, peritoneal dialysate leakage, skid of outer cuff,
      incidence of inguinal hernia and bellyache, etc, no significant difference
      existed between two groups (p > 0.05). The two groups had the same 12-month
      technical survival rate of 92.73%. The 12-month survival rate for Group A was
      86.34% while the corresponding figure for Group B was 80.68% (p > 0.05).
      CONCLUSIONS: Infections, mechanical complications, technical survival rate and
      patients' survival rate were quite similar, when a Swan neck catheter and a
      Tenckhoff catheter were used in Chinese CAPD patients.

PMID- 19863881
TI  - Therapeutic equivalence, long-term efficacy and safety of HX575 in the treatment
      of anemia in chronic renal failure patients receiving hemodialysis.
AB  - BACKGROUND: The recombinant human epoetin-a HX575 (Sandoz Pharmaceuticals
      GmbH/Hexal AG, Holzkirchen, Germany) is the first biosimilar erythropoiesis
      stimulating agent (ESA) with marketing authorization in Europe. The primary
      objective of the study was the evaluation of therapeutic equivalence in terms of
      hemoglobin (Hb) response of HX575 compared with the comparator product (EPREX/
      ERYPO, Janssen-Cilag/Ortho Biotech, Neuss, Germany) in the long-term intravenous
      (i.v.) treatment of anemia in chronic renal failure patients on hemodialysis
      following a 1 : 1 dose conversion from the comparator product to HX575. METHODS:
      Hemodialysis patients with Hb levels of 10.0 - 13.0 g/dl were randomized to
      either continue their current i.v. epoetin-a treatment or switch to HX575. During
      treatment, epoetin dosages were titrated to maintain Hb values. The primary
      endpoint was the difference between treatment groups in the mean absolute change
      of Hb levels between baseline and evaluation period (Weeks 25 - 28). RESULTS:
      Therapeutic equivalence of HX575 and the comparator epoetin-alpha, assessed
      during the evaluation period, was statistically confirmed: mean changes in Hb
      levels were 0.15 +/- 0.09 g/dl in the HX575 and 0.06 +/- 0.12 g/dl in the
      comparator epoetin-a group, with a difference between groups of 0.08 g/dl (95%
      confidence interval: -0.17; 0.34). Hb levels and epoetin dosages remained stable
      throughout the entire study period of 56 weeks. The long-term safety profile of
      HX575 was similar to that of the comparator epoetin-alpha. No antibody formation
      was detected. CONCLUSIONS: The study demonstrated therapeutic equivalence of
      biosimilar HX575 to the comparator epoetin-a, together with a comparable safety
      profile.

PMID- 19863882
TI  - A case with spontaneous bladder rupture mimicking acute kidney injury.
AB  - A 77-year-old female with abdominal pain and ascites was admitted to our
      hospital. She had a past history of the postoperative pelvic irradiation for
      uterine cancer and subsequently suffered from neurogenic bladder. On admission,
      serum creatinine (s-Cr) and blood urea nitrogen (BUN) were elevated to 9.9 mg/dl
      and 131 mg/dl, respectively. However, both the ratio of BUN/s-Cr and creatinine
      in ascites/s-Cr were significantly elevated. The clinical manifestations of the
      present case were not typical for acute kidney injury. Furthermore, 2 days after
      urethral catheterization, both s-Cr and BUN were normalized (0.69 mg/dl and 10
      mg/dl, respectively) and her symptoms had improved immediately. Therefore, we
      diagnosed her disease as spontaneous bladder rupture. We report a case with
      spontaneous bladder rupture mimicking acute kidney injury forty years after
      postoperative pelvic irradiation for uterine cancer.

PMID- 19863883
TI  - Intraperitoneal bladder rupture presenting as acute bloody ascites and oliguric
      acute renal failure in an alcoholic liver cirrhosis patient.
AB  - Intraperitoneal bladder rupture is a rare cause of acute abdomen with bloody
      ascites. We report herein the case of a patient who had alcoholic liver cirrhosis
      and multiple liver nodules, and experienced acute bloody ascites and oliguric
      acute renal failure in association with intraperitoneal bladder rupture. A 33
      year-old male suffered from acute abdominal pain and oliguria following
      consumption of a large amount of alcohol and after blunt abdominal trauma. He was
      also found to have acute renal failure and newly onset bloody ascites that
      rapidly subsided following transurethral catheter drainage. Computed tomography
      cystography revealed intraperitoneal extravasation of contrast from the dome of
      the bladder, suggestive of intraperitoneal bladder rupture. The patient received
      surgical repair and was discharged with full recovery. This case shows that it is
      important for physicians to be aware of the possibility of intraperitoneal
      bladder rupture after alcohol consumption accompanied with abdominal blunt
      trauma. In particular, it has diagnostic complications for underlying liver
      tumors.

PMID- 19863884
TI  - Evolution of light chain deposition disease over 8 years.
AB  - A 44-year-old female was diagnosed with proteinuria due to nodular
      glomerulosclerosis secondary to light chain deposition disease (LCDD). After 6
      years, deterioration of kidney function occurred and autologous stem cell
      transplantation was considered, but the patient refused specific therapies. The
      disease progressed slowly, over a period of 8 years reaching now chronic renal
      insufficiency stage 4 with a creatinine clearance of 20 ml/min, in spite of no
      specific therapy. This case, documented by repeated biopsies, demonstrates the
      very slow loss of kidney function, suggesting the possibility of conservative
      treatment strategies without taking the risks of chemotherapy or autologous stem
      cell transplantation, since no long term follow up data of these therapies are
      available for LCDD.

PMID- 19863885
TI  - Fish, flesh and a good red herring: a case of ascending upper limb infection in a
      renal transplant patient.
AB  - While newly developed potent immunosuppressive agents have dramatically reduced
      the incidence of rejection of transplanted organs, they have increased the
      patients' susceptibility to opportunistic infections and cancer. Here we report a
      rare skin infection caused by atypical mycobacterium marinum in a 50-year-old
      female renal transplant recipient. The patient presented with localized skin
      lesion on the dorsum of her hand, which was misdiagnosed as gout. Only after the
      lesions spread in a sporotrichoid pattern, a cutaneous infection with atypical
      mycobacteria was suspected. The diagnosis was based on histopathological analysis
      as well as mycobacterial culture, both showing infection with atypical
      mycobacterium. Three months of antimycobacterial treatment led to a marked
      regression of the lesions. Sporotrichoid lesions in renal transplant patients are
      rare and a diagnostic challenge for the physician. A thorough history and a low
      threshold for skin biopsies could prevent painful and unnecessary surgical
      interventions.

PMID- 19863886
TI  - A case of endocarditis of difficult diagnosis in dialysis: could "pest" friends
      be involved?
AB  - We report a case of A. xylosoxidans endocarditis of larvate clinical presentation
      in a central venous catheter-dependent hemodialysis patient of difficult
      diagnosis and poor evolution despite a high index of suspicion and consequent
      assessment. A 50-year-old man on hemodialysis presented with inflammatory
      malnutrition parameters during the months prior to diagnosis of endocarditis,
      whilst he was otherwise asymptomatic. No vegetations were detectable on his
      cardiac valves at repeated echocardiography until third transesophageal
      echocardiography was performed, and confirmed intraoperatively. On the occasion
      of positive peripheral blood culture for Alcaligenes (Achromobacter)
      xylosoxidans, the etiological diagnosis was retrospectively explained given his
      history of animal exposure - hunting rabbits using his pet ferrets. This
      bacterium is an emergent and resistant organism, mostly related to nosocomial
      infections and environmental water sources. Reservoirs include the microflora of
      the nasal cavity of rabbits and the dentogingival sulcus of ferrets. We presume
      that A. xylosoxidans endocarditis was transmitted from the patient's pets. It
      highlights the importance of early recognition of an inflammatory status and
      investigation of the underlying cause. Additionally, the causative bacterium
      emphasizes the importance of registering exposure to animals in CVC-dependent
      patients as well as the need for their awareness of hygienic precautions and the
      infectious risk associated to catheters.

PMID- 19863887
TI  - Isolated sarcoid granulomatous interstitial nephritis in pediatrics: a case
      report and review of literature.
AB  - Sarcoidosis is a multisystem disease of unknown etiology primarily affecting the
      lungs, skin, and lymph nodes. The disease usually manifests in young adults and
      is uncommon in childhood. Renal involvement, including granulomatous interstitial
      nephritis (GIN), is rare, and few cases of isolated sarcoid GIN have been
      reported in pediatrics. We report a case and review the literature.

PMID- 19863888
TI  - Treatment of hyper-IgG4 disease with sequential corticosteroids and tamoxifen -
      case report and review of the literature.
AB  - We report a patient with multifocal fibrosclerosis presenting as sialadenitis,
      hepatic fibrosis, and retroperitoneal fibrosis with renal failure. His medical
      management consisted of prednisone (4 months at 40 mg daily, then tapered down to
      5 mg daily for another 14 months) and 18 months of tamoxifen. He responded
      clinically and radiographically to this regimen, and remains in clinical
      remission 10 months after discontinuing medical therapy. Subsequent histologic
      examination of submandibular gland tissue revealed strong staining for IgG4
      positive plasma cells. To our knowledge, this is the first case of confirmed
      multifocal hyper-IgG4 disease to be successfully treated with sequential
      corticosteroids and tamoxifen.

PMID- 19863889
TI  - Hydroureteronephrosis caused by endometriosis around the ureter.

PMID- 19863890
TI  - Cutaneous Kaposi's sarcoma following immunosuppressive therapy for
      membranoproliferative glomerulonephritis.

PMID- 19863891
TI  - Pie-shaped corpora aliena in a dialysis patient.

PMID- 19863892
TI  - Validity of scoring caries and primary molar hypomineralization (DMH) on
      intraoral photographs.
AB  - AIM: The aims of this study were to assess whether intraoral photographs could be
      used to score caries and hypomineralization on primary molars (Using adapted
      Molar Incisor Hypomineralization (MIH)-criteria), and also to assess the
      reliability and validity in 3-7 year-old Dutch children of these scores by
      comparing them to direct clinical scorings. STUDY DESIGN: Cross-sectional study.
      METHODS: In this study 62 children (38.7% girls) with a mean age of 4.96 years
      (SD 1.27) participated. The children were rated clinically by their own dentist
      (authors JV or ME) for caries reaching the dentine in their primary molars (WHO
      criteria) and also for primary molar hypomineralization using the adapted MIH
      criteria. For the intraoral photographs, a digital intraoral camera was used. The
      two paediatric dentists rated all the intraoral photographs on caries and
      hypomineralizations on the second primary molars, using the same criteria for the
      clinical scoring as for the scoring of the photographs. They scored
      independently, at least 2 weeks after the initial clinical scoring to avoid
      observational bias with the clinical scoring. STATISTICS: This clinical
      observation was used as the gold standard from which sensitivity, specificity,
      Positive Predictive Value (PPV), Negative Predictive Value (NPV) and the Positive
      and Negative Likelihood Ratio were computed. To test the intra-observer agreement
      25 % of the photographs were scored again, at least 2 weeks after the initial
      scoring of the images. Inter- and intra-observer agreement were tested using
      Cohen's Kappa. RESULTS: The mean prevalence of clinically detected caries at
      tooth level was 46.7% and the mean prevalence of clinically detected
      hypomineralizations in second primary molars at tooth level was 21.8%. The
      sensitivity of assessing caries using intraoral photographs was 85.5%, the
      specificity 83.6%, the positive likelihood ratio 5.2 and the negative likelihood
      ratio was 0.17. For Primary Molar Hypomineralization (DMH) the sensitivity was
      72.3%, the specificity 92.8%, the positive likelihood ratio 10.1 and the negative
      likelihood ratio was 0.30. The inter-observer agreement yielded the following
      Cohen's Kappa scores: for caries 0.76 and for DMH 0.62. The intra-observer
      agreement was for caries 0.80 (ME) and 0.72 (JV) and for DMH 0.95 (both ME and
      JV). CONCLUSIONS: From this investigation it was concluded that the sensitivity,
      specificity and the likelihood ratio of scoring caries and DMH on photographs
      made with an intraoral camera were good. The inter- and intra-observer
      reliability for caries and DMH were good to excellent. These findings suggest
      that intraoral photographs may be used in clinical practice and large
      epidemiological studies.

PMID- 19863893
TI  - Histological validation of a laser fluorescence device for occlusal caries
      detection in primary molars.
AB  - AIM: This was to validate in vitro a laser fluorescence device, DIAGNOdent 2095 -
      DD, on the detection of occlusal caries in primary molars using the histological
      examination as the gold standard and to compare the laser fluorescence findings
      to the results of the conventionally used diagnostic methods. STUDY DESIGN AND
      METHODS: 111 occlusal pits in 24 extracted primary molars were examined for
      caries by one trained operator (Intra-examiner Reliability K>0.83), using direct
      visual (DV), indirect visual (IDV), radiographic (XR) and fluorescence (DD)
      examinations and then the extent of caries was determined histologically.
      Sensitivity, specificity, accuracy and the area under the ROC curve - AUC were
      calculated for all methods, using the histological evaluation as the gold
      standard. STATISTICS: Differences between examination methods were estimated by
      pair-wise comparison of their respective AUC. RESULTS: DD's sensitivity for
      enamel and for dentine lesions respectively was 0.90 and 0.36, its specificity
      0.36 and 0.91 and its accuracy 0.61 and 0.65. The DD device exhibited better
      sensitivity than specificity for enamel lesions and better specificity than
      sensitivity for lesions into dentine. The DD device was found to have the highest
      sensitivity for lesions into enamel, specificity and accuracy and as well as the
      largest AUC compared with all other methods. For lesions into dentine however,
      according to AUC values the DD was not statistically significant different from
      the other methods. CONCLUSION: Compared with the other methods, the DD had the
      highest validity for enamel caries while its validity for caries into dentine was
      not statistical different from the other methods.

PMID- 19863894
TI  - Prevalence of symptoms and signs indicative of temporomandibular disorders in
      children and adolescents. A cross-sectional epidemiological investigation
      covering two decades.
AB  - AIMS: These were to 1) estimate the prevalence of subjective symptoms and
      clinical signs of temporomandibular disorders (TMD) in children and adolescents
      in the city of Jonkoping, Sweden, 2) follow possible variations in TMD signs and
      symptoms over a 20-year period, and 3) study possible associations between TMD
      symptoms and signs and factors of interest. DESIGN: About 100 individuals in the
      age groups of 3, 5, 10 and 15 years participated in cross-sectional stratified
      epidemiological investigations in 1983, 1993 and 2003. METHODS: All participants
      were asked to fill in a questionnaire including questions on general and oral
      health, dental care habits and some socio-demographic issues. More specific
      questions recorded the presence or absence of subjective symptoms: tiredness in
      the jaws on awakening or during chewing; clicking sounds or crepitations from the
      temporomandibular joints (TMJs); locking/ catching of the mandible; luxation of
      the mandible; reduced jaw movement capacity; pain during jaw movements; other
      pain conditions in the jaws or in the TMJ regions. Subjects were examined
      clinically at each time period for; jaw mobility (maximum jaw opening including
      vertical overbite, maximum laterotrusion to the right and to the left, maximum
      protrusion); TMJ function (normal function, deflection on jaw opening of >2 mm,
      TMJ clicking or crepitations, TMJ locking, TMJ luxation); pain on jaw movement
      (no pain on movements, pain on one movement, pain on more than one movement);
      muscle pain (no muscle pain, pain on palpation in 1-3 sites, pain on palpation in
      >3 sites); TMJ pain (no joint pain, pain on lateral palpation of one or both
      joints, pain on posterior palpation of one or both joints). No functional
      examination of the masticatory system was performed in children aged 3 and 5
      years. RESULTS: TMD-related symptoms were very rare in 3- and 5-year-olds. In the
      age groups of 10- and 15-year olds, 5-9% of the participants reported more severe
      symptoms, up to 50% showed one or more TMD signs, while it was estimated that 1
      2% were in need of TMD treatment. Several symptoms and signs increased with age.
      No gender differences, with the exception of recurrent headache, were noted. Oral
      parafunctions were reported by 11-47%. Apart from a few variables, no
      statistically significant changes in the prevalence of TMD symptoms and signs
      were observed over the 20-year period. Clenching/grinding of teeth and general
      health factors were found to be associated with TMD symptoms and signs.
      CONCLUSIONS: The prevalence of more severe TMD symptoms and signs in children and
      adolescents was generally low in all three examinations and did not change
      significantly during the 20-year period. Increasing age, general health factors
      and oral parafunctions were associated with TMD symptoms and signs in 10- and 15
      year-olds.

PMID- 19863895
TI  - Case series: Treatment considerations in x-linked hypohidrotic ectodermal
      dysplasia.
AB  - AIMS: To describe our treatment considerations obtained from the dental care of
      several boys affected with X-linked hypohidrotic ectodermal dysplasia (HED) and
      to discuss the different problems that may arise in connection with these kinds
      of treatments. STUDY DESIGN: The subject group included 10 males affected with X
      linked HED, treated at the department of Paediatric Dentistry and Clinical
      Genetics, Copenhagen School of Dentistry. All patients were treated, after a
      period of adaptation, with removable prostheses and whenever necessary, composite
      restoration of the conical crown morphology of the maxillary incisors.
      Furthermore, some of the patients received an orthodontic treatment for
      closure/reduction of the medial diastema. RESULTS: The mean number of
      appointments at the department was 32 with a range from 7 to 59 appointments. In
      7 out of 10 patients, the treatment was a success according to the patient,
      parents and dentist. In 3 out of 10 patients the treatment was not a success from
      the dentist's point of view: primarily due to lack of cooperation between the
      patient, parents and dentist. In half of the patients the deviated maxillary
      incisors morphology was restored and 5 out of 10 patients received orthodontic
      treatment for closure of the medial diastema in the maxilla. CONCLUSION: It is of
      utmost importance to take the motivation of the patient and parents as well as
      the patient's acceptance for dental treatment into consideration. Furthermore,
      the treatment is rather time-consuming and should involve different areas of
      specialisation. Finally it is vital to remember that the parents may also have
      undergone a prolonged dental treatment, which might reduce their patience
      regarding their children's treatments.

PMID- 19863896
TI  - Case report: Report of a rare case of juvenile recurrent parotitis and review of
      literature.
AB  - BACKGROUND: Juvenile recurrent parotitis (JRP) is a rare salivary gland disease
      of obscure aetiology that affects children. It is characterized by multiple
      episodes of unilateral or bilateral parotid inflammation over a period of years.
      CASE REPORT: A 14 year old boy presented with multiple episodes of recurrent
      bilateral swellings of the parotid glands since 1 year of age with no relevant
      past medical and dental history, TREATMENT: Included prescription of antibiotic
      Dicloxacillin 500 mg tid for 7 days and analgesics as a combination of Diclofenac
      50 mg and Paracetamol 500 mg tid for 10 days, to resolve acute infection followed
      by sialography using Iopromide (ultravist-300) twice at an interval of 6 months
      for glandular lavage which helps to clear the mucous plugs that form during the
      acute phase. FOLLOW-UP: It was satisfactory as there has been no recurrence of
      parotitis during 18 months.

PMID- 19863897
TI  - Case report: Presentation of lacrimo-auriculodento- digital (LADD) syndrome in a
      young female patient.
AB  - BACKGROUND: Lacrimo-auriculo-dento-digital (LADD) syndrome (OMIM #149730) is an
      autosomal-dominant congenital disorder that can be caused by heterozygous
      mutations in the tyrosine kinase domains of the genes encoding fibroblast growth
      factor receptors 2 (FGFR2) and 3 (FGFR3), and has been found in association with
      a mutation in the FGF10 gene, which encodes an Fgfr ligand. Clinical signs vary,
      but the condition is characterised by involvement of the lacrimal and salivary
      systems, cup-shaped ears, hearing loss and dental abnormalities. Additional
      features may include involvement of the hands and feet with other body systems
      particularly the kidneys. CASE REPORT: Previous literature on the subject has
      been reviewed and this case is the first presentation of LADD syndrome in the
      Republic of Ireland, as a sporadic case in a 12-year-old girl who exhibited a
      range of dental and digital anomalies. TREATMENT: Her general medical
      practitioner managed her medical care whilst her oral care necessitated a
      multidisciplinary approach involving restorative and orthodontic elements. FOLLOW
      UP: The initial restorative phase of treatment has successfully improved the
      appearance of the patient's anterior teeth using direct resin composite build
      ups.

PMID- 19863898
TI  - Short communication: Graph for calculating maximum local analgesic dose in
      millilitres for the paediatric population.
AB  - AIM: Determination of the maximum local analgesic dosage in millilitres can be
      confusing. This article presents a new graph that easily allows the dental
      practitioner to determine a child's maximum local analgesic dosage in millilitres
      based on their weight. BACKGROUND: Local analgesia is used daily in dentistry to
      manage pain, and different kinds of agents are available in the market that may
      be selected depending on the strength and duration of analgesia required. Each
      analgesic agent has a maximum recommended dose, and it is very important to
      calculate that dose, especially in children, to avoid the risk of toxicity that
      could lead to death. Currently a series of calculations are used to calculate the
      maximum recommended dose for local analgesic agents that could be taxing. This
      paper presents a newly-developed graph that makes it easier for dental
      practitioners to quickly identify the maximum recommended dose of the different
      local analgesic agents used in dentistry based on a patient's weight. CONCLUSION:
      Dentists can utilize this graph to obtain the maximum local analgesic dose in
      millilitres based on the child's weight. This will save time and encourage
      dentists to routinely identify the maximum allowed dose and most importantly,
      decrease or eliminate the risks of toxicity and overdose especially when treating
      small children.

PMID- 19863899
TI  - Short Communication: In vitro evaluation of the abrasiveness of acidic
      dentifrices.
AB  - AIM: This in vitro study evaluated the abrasiveness of acidic fluoride (F)
      dentifrices with different F concentrations on bovine enamel. METHODS: Enamel
      blocks (4.0 x 4.0 mm2, n=120) were selected according to their surface
      microhardness and divided into 12 groups. Slurries of dentifrices were used
      containing 0 (placebo), 275, 412, 550 and 1,100 ppm F (pH 4.5 or 7.0), as well as
      testing two commercial dentifrices (Crest, positive control, 1,100 ppm F and
      Colgate Baby, 500 ppm F). Enamel blocks were partially protected with an adhesive
      tape (control area) and then brushed by an automated toothbrushing machine
      (16,000 strokes). During this process, 0.4 ml of the slurries were injected every
      2 mins on the enamel blocks. After toothbrushing, enamel wear was determined by
      profilometry. STATISTICS: Results were analyzed by ANOVA and Tukey's test
      (p<0.05). RESULTS: The mean values for pH in the suspensions during treatment
      were 6.93, 4.32, 7.56 and 8.19 for neutral experimental dentifrices, acidic
      experimental dentifrices, Crest and Colgate baby, respectively. The abrasiveness
      of the acidic dentifrices was similar (p<0.05) to the neutral ones, whereas
      commercial dentifrices yielded lower abrasion (p<0.05). CONCLUSION: It was
      concluded that a reduction of the pH of dentifrices does not increase their
      abrasiveness.

PMID- 19863900
TI  - Case report: Surgical luxation and elevation as treatment approach for secondary
      eruption failure of permanent molars.
AB  - BACKGROUND. Secondary eruption failure of permanent molars is a rare disturbance
      that usually causes serious clinical problems to the patient. Various treatment
      approaches have been proposed that depend on the age of the patient, the
      developmental stage of the root, the position of the tooth, the severity of
      infraocclusion and the presence of one or more affected teeth. Surgical luxation
      followed by elevation and stabilization of the luxated tooth has been proposed as
      a first-step treatment in cases of young patients with incomplete root formation
      and favourable position of the tooth. CASE REPORT. A boy initially aged 7.5 years
      old presented with localized secondary eruption failure of the mandibular right
      first permanent molar (46) and infra-occlusion. The medical and dental history of
      the child was uneventful, while there was no history of eruption failure or
      ankylosis in any other family member. TREATMENT. This included surgical luxation
      of the tooth, followed by elevation to the occlusal plane and immobilization to
      the adjacent primary molar. The splint was removed after 4 weeks. FOLLOW-UP.
      Three years follow-up revealed a successful result with no clinical or
      radiological pathology of the area. Root development of the affected tooth was
      arrested, but there was no sign of pulp necrosis. CONCLUSION. Favourable
      treatment outcome using surgical luxation and repositioning of the teeth in the
      present case of permanent molar with secondary eruption failure was observed.

PMID- 19863901
TI  - Case report: Cone-beam ct imaging in the management of a double tooth.
AB  - BACKGROUND: The diagnosis and management strategies of double teeth have largely
      relied on clinical examination and conventional radiographic findings. Cone-Beam
      Computed Tomography (Cone-beam CT) was developed in the late 1990's and,
      therefore, is a relatively recent addition to the imaging armamentarium for use
      in Maxillofacial Radiology. There have been no publications in the dental
      literature demonstrating the use of Cone-beam CT or 3D stereolithography in the
      diagnosis and surgical planning of the management of double teeth. CASE REPORT:
      An 11 year old girl presented with a double left lateral maxillary incisor.
      Conventional plain film radiography failed to provide the requisite information
      for pre-operative planning. Cone-beam Computed Tomography (Cone-beam CT) allowed
      determination of location of fusion, three-dimensional (3D) visualisation of
      pulpal anatomy and the construction of a 3D stereolithographic model for surgical
      planning. The double tooth was surgically divided in situ under local analgesia.
      The redundant distal unit was extracted and the residual mesial unit built up in
      composite resin following physiological mesial drift of displaced maxillary left
      canine. No endodontic therapy was required. FOLLOW-UP: At a 10-month follow-up
      visit, clinical and radiographic vitality and success was noted. CONCLUSION: The
      great amount of radiological information which Cone-beam CT can offer not only
      improves pre-operative and surgical planning, but the 3D models provided can be
      used to further educate and inform patients and guardians in the management of
      double teeth.

PMID- 19863902
TI  - Characterization of pentraxin 3 in the horse and its expression in airways.
AB  - The long pentraxin 3 (PTX3) plays an important role in host defence and its over
      expression may contribute to airway injury. The aim of the present study was
      therefore to characterize in more detail PTX3 and its expression in the horses'
      airway. Six healthy horses and six horses affected by recurrent airway
      obstruction (R.A.O.) were submitted to a dusty environment challenge. PTX3 DNA
      and cDNA were cloned and sequenced. PTX3 expression was evaluated by RT-qPCR,
      Western blotting and immunohistochemistry in bronchoalveolar lavage fluid (BALF)
      cells, BALF supernatant and bronchial epithelial cells. An alternative splicing
      of the second exon of PTX3 occurred, resulting in two forms of the protein:
      "spliced" (32 kDa) and "full length" (42 kDa). PTX3 was detected in BALF
      macrophages, neutrophils and bronchial epithelial cells. It was over-expressed in
      the BALF supernatant from R.A.O.-affected horses in crisis. However, dust was
      unable to induce PTX3 in BALF cells ex vivo, indicating that dust is an indirect
      inducer of PTX3. Dust exposure in-vivo induced PTX3 in BALF macrophages but there
      was no significant difference between healthy and R.A.O.-affected horses.
      Conversely, PTX3 was over-expressed in the bronchial epithelial cells from R.A.O.
      affected horses in crisis. These data indicate a differential regulatory
      mechanism in inflammatory and bronchial epithelial cells and offer
      therapeutically interesting perspectives.

PMID- 19863903
TI  - Comparison of two modern vaccines and previous influenza infection against
      challenge with an equine influenza virus from the Australian 2007 outbreak.
AB  - During 2007, large outbreaks of equine influenza (EI) caused by Florida
      sublineage Clade 1 viruses affected horse populations in Japan and Australia. The
      likely protection that would be provided by two modern vaccines commercially
      available in the European Union (an ISCOM-based and a canarypox-based vaccine) at
      the time of the outbreaks was determined. Vaccinated ponies were challenged with
      a representative outbreak isolate (A/eq/Sydney/2888-8/07) and levels of
      protection were compared.A group of ponies infected 18 months previously with a
      phylogenetically-related isolate from 2003 (A/eq/South Africa/4/03) was also
      challenged with the 2007 outbreak virus. After experimental infection with
      A/eq/Sydney/2888-8/07, unvaccinated control ponies all showed clinical signs of
      infection together with virus shedding. Protection achieved by both vaccination
      or long-term immunity induced by previous exposure to equine influenza virus
      (EIV) was characterised by minor signs of disease and reduced virus shedding when
      compared with unvaccinated control ponies. The three different methods of virus
      titration in embryonated hens' eggs, EIV NP-ELISA and quantitative RT-PCR were
      used to monitor EIV shedding and results were compared. Though the majority of
      previously infected ponies had low antibody levels at the time of challenge, they
      demonstrated good clinical protection and limited virus shedding. In summary, we
      demonstrate that vaccination with current EIV vaccines would partially protect
      against infection with A/eq/Sydney/2888-8/07-like strains and would help to limit
      the spread of disease in our vaccinated horse population.

PMID- 19863904
TI  - [Drugs and heat wave: SIRIUS, a multicentric case-control study in patients older
      than 65 years during 2007 summer in France].
AB  - OBJECTIVE: To evaluate in real conditions the role of drugs in heat-related
      adverse effects. METHODS: We performed a multicentric case-control study in 3
      university hospitals in France, including 36 cases (patients older than 65 years
      hospitalized with hyperthermia or dehydration between 1st July and 31st August
      2007) and 51 controls. We compared drugs and changes in drug dosage according to
      the values of renal function. RESULTS: At inclusion, clearance creatinine was
      available for only 12 patients (mean = 31.6 ml/min), and three-fold higher in
      controls (p < 0.001). Cases took more drugs than controls (4.3 vs. 3.9; p <
      0.001), particularly neuroleptic drugs (3.6% vs. 0.5%; p = 0.007). CONCLUSION:
      Despite its small size, our study shows that patients suffering from dehydration
      in summer are those with more severe renal impairment, taking more drugs
      (particularly neuroleptics). This pilot work could allow to improve methodology
      of further studies on drugs during heat waves.

PMID- 19863905
TI  - [Security in medication use process: state-of-play report in 21 hospital
      pharmacies in Aquitaine (France)].
AB  - BACKGROUND: Failures may occur in each part of the medication use process. This
      study aimed to evaluate the barriers existing in hospital pharmacies in order to
      prevent medication errors and to help institutions to make improvement actions.
      METHODS: Within the framework of the SECURIMED project, risk assessment visit
      (interviews, observations, analysis of adverse event scenario by
      professionals...) were conducted in volunteer hospital pharmacies. A restitution
      meeting, after visit in each pharmacy permitted exchanges between visitors and
      professionals on barriers and weaknesses and then on solutions to reduce
      identified risks. RESULTS: Twenty-one hospital pharmacies participated. Despite
      presence of safeguards in some pharmacies, many weaknesses were retrieved
      (multiplicity of process, lack of resources...) and clinical pharmacy was not
      enough developed. CONCLUSION: This project has led to an overview of the
      situation in Aquitaine, and created a regional dynamic to improve the medication
      system safety.

PMID- 19863906
TI  - [Assessment of inappropriate prescriptions in psychiatric in-patients].
AB  - OBJECTIVE: To evaluate occurrence of the inappropriate prescriptions in a
      psychiatric department. METHODOLOGY: In this prospective survey over a two-month
      period, the medical orders were analysed. Inappropriate prescription was defined
      as any discrepancy with summary of product characteristics (SPC) or our hospital
      treatment guidelines. RESULTS: One hundred inpatients (72 women, mean age 37.5+/
      15 years) were included. We reviewed 495 medication orders, which represent 1875
      prescribed drugs. We found 2636 discrepancies with SPC or our hospital treatment
      guidelines. The proportion of discrepancies related to legal informations was
      21.28% and them related to pharmacotherapy was 55.04%. The proportion of
      discrepancy per patient was estimated to 4.93%. CONCLUSION: Our study shows a
      high proportion of inappropriate prescriptions, none of them having induced
      adverse-drug effects.

PMID- 19863907
TI  - [Juvenile myoclonic epilepsy with recurrent myoclonic status: efficacy of
      valproate].
AB  - Juvenile myoclonic epilepsy (JME) is characterized by a specific pharmacological
      sensitivity. JME is controlled by certain antiepileptic drugs but may be
      aggravated by others. Valproate is the treatment of choice of this epilepsy.
      Among the "newer" antiepileptic drugs those that appear to be useful are
      lamotrigine, topiramate, zonisamide and levetiracetam. We present a patient with
      JME who experienced myoclonic status epilepticus every months not controlled with
      lamotrigine monotherapy (200 mg/d), not controlled with levetiracetam monotherapy
      (1000 mg/d). Addition of valproate (500 mg/d) to levetiracetam fully controlled
      the seizures and levetiracetam was reduced to 500 mg/d. The patient is presently
      seizure free.

PMID- 19863908
TI  - [Human toxicokinetic of hexobarbital after acute multi-drug intoxication].
AB  - A 33-year-old man was hospitalized unconscious on suspicion of acute diazepam and
      hexobarbital intoxication, a barbiturate not marketed in France. Its
      quantification was developed by gas chromatography coupled with mass spectrometry
      detection and validated on one-hundred microL of plasma extracted by a
      liquid/liquid method. Hexobarbital and diazepam concentrations in initial plasma
      samples were at toxic levels, respectively 15 900 ng/mL and 13 800 ng/mL.
      Hexobarbital toxicokinetic was studied during 175 h and analysed with a non
      compartmental model. Half-life value of 61,8 h was found, being much longer than
      already published hexobarbital half-lives (between 3.2 h and 6.9 h). The reasons
      of this long half-life were discussed according to metabolism and
      pharmacogenetic.

PMID- 19863909
TI  - [Immediate and delayed hypersensitivity reactions to iodinated radiographic
      contrast agents: an update].
AB  - Diagnostic and interventional radiology of patients is nowadays crucial with
      increasing requirement for iodinated contrast agents infusion. Besides adverse
      reactions after administration of the iodinated contrast agents due to their
      toxicity, immediate hypersensitivity reactions and reactions resembling delayed
      hypersensitivity appearing from 1 hour to several days later, have been reported.
      Patients at high risk to develop such adverse events have to be detected on the
      basis of their risk factors in order to prevent or limit serious outcomes.
      Previous reactions to contrast media, asthma, atopy and cardiovascular disorders
      are risk factors for anaphylactic or anaphylactoid reactions. Female gender, age
      and beta-blockers increase the severity. This article aims to summarize the risk
      of allergic reactions related to the use of iodinated contrast agents and to
      suggest a way for diagnosis, treatment and prevention according to each clinical
      situation.

PMID- 19863911
TI  - The role of proficiency testing in achieving standardization and harmonization
      between laboratories.
AB  - OBJECTIVES: Proficiency testing is part of a quality system that provides
      external assessment that a laboratory's performance meets clinical requirements.
      DESIGN AND METHODS: A set of samples, intended to simulate clinical samples, is
      provided to a group of laboratories. The samples are measured for specified
      measurands and the results reported to the organizing body. Target values are
      assigned by the organizing body typically as the mean response of a group of
      laboratories that use similar measurement technology; or, when samples are
      commutable with native clinical samples, by a reference measurement procedure.
      RESULTS: Each participant's results are compared to the target values to
      determine if a laboratory's results are in conformance to the expectations for
      clinically acceptable results. When commutable samples are used, results can be
      compared to reference measurement procedure values to evaluate trueness.
      Unacceptable results are investigated and corrective action taken. CONCLUSION:
      Proficiency testing allows an individual laboratory to evaluate if its
      performance is satisfactory for the intended clinical purpose. Comparison of
      results among laboratories allows evaluation of the effectiveness of calibration
      procedures in the field.

PMID- 19863912
TI  - Traceability as a unique tool to improve standardization in laboratory medicine.
AB  - The standardization of measurements is of high priority in Laboratory Medicine,
      its purpose being to achieve closer comparability of results obtained using
      routine analytical systems. In order to achieve standardization, an approach is
      required that provides reliable transfer of the measurement values from the
      highest hierarchical level to methods which are routinely used in the clinical
      laboratories. Such a structure is presented by the reference measurement system
      (RS), based on the concepts of metrological traceability. Key elements of a
      comprehensive RS are the reference measurement procedure and reference materials.
      Other essential elements include the definition of the measurand in regards to
      the intended clinical use and the reference laboratories that may collaborate in
      a network. At present, there is international cooperation in developing RS for
      analytes of clinical significance. Thanks to the work of the Joint Committee on
      Traceability in Laboratory Medicine (JCTLM), a list of higher order reference
      materials and reference methods is now publicly available. JCTLM has also
      published the list of reference laboratories that are able to deliver a reference
      measurement service. As soon as a new RS is implemented, clinical validation of
      the correctly calibrated routine methods (the IVD products sold onto the market)
      should take place. Other important issues concerning the implementation of a
      metrologically-correct approach for result standardization are: 1) the clear
      definition of the clinically allowable error of measurements and 2) the post
      market surveillance of the performance of IVD products. These are tasks of our
      profession through the organization of appropriate External Quality Assessment
      programs.

PMID- 19863910
TI  - [Homage to Professor Pierre Simon].

PMID- 19863913
TI  - Traceability and standardization of immunoassays: a major challenge.
AB  - The clinical utility of immunoassay results is dependent on precision and
      trueness for the application of internationally agreed clinical protocols and
      common reference intervals and decision limits. The application of metrological
      principles to achieve traceability and standardization for these assays is being
      pursued to this end. Comprehensive measurement systems are available for a number
      of the total serum hapten assays routinely measured by immunoassays while current
      research is investigating the appropriateness of developing defined systems for
      the measurement of "free" hormone levels. The standardization or harmonization of
      assays for heterogeneous polypeptide hormones is also another area of research
      for these assays.

PMID- 19863914
TI  - The 2007 International Vocabulary of Metrology (VIM), JCGM 200:2008 [ISO/IEC
      Guide 99]: Meeting the need for intercontinentally understood concepts and their
      associated intercontinentally agreed terms.
AB  - Unambiguous and consistent concepts and terms such as measurand, metrological
      traceability, measurement uncertainty, comparability of measurement results,
      target measurement uncertainty, etc., must govern the description of measurements
      in order to enable a valid comparison of measurement results. That is not yet the
      case as numerous workshops over the last decade have shown worldwide and as
      chemical literature continuously displays. For international trade in food and
      feed to be fair, for border-crossing implementation of environmental regulations
      to be the same for all parties concerned, for interchangeability of results of
      clinical measurements to become a reality, for any border-crossing interpretation
      of measurement results in chemistry to become possible, well understood and
      mutually accepted, common and well defined concepts and terms are essential.
      Similarly, their translations from one language--English--to 30-40 other
      languages, must be realized and fixed unequivocally. Countries using English as
      common language have not yet fully realized that they are at a considerable
      advantage over countries where such translated terms describing concepts may not
      yet be available, let alone understood and accepted. A number of ambiguities in
      the definitions and terms are described which illustrate the importance of the
      revision (1997-2007) of the International Vocabulary of Metrology (VIM),
      henceforth conveniently called "VIM3", especially since chemical measurement is
      covered in this VIM for the first time in history: 'measurand' 'metrological
      comparability of measurement results' 'metrology' 'metrological compatibility of
      measurement results' 'measurement result' 'metrological traceability' (incl 'to
      the SI') 'measurement uncertainty' 'target measurement uncertainty' 'calibration
      hierarchy' 'quantity' and many others. It is concluded that the revised VIM is of
      primordial importance for good understanding within and between the measurement
      communities worldwide.

PMID- 19863915
TI  - Laboratory quality regulations and accreditation standards in Canada.
AB  - OBJECTIVES: To review the current status of laboratory quality regulations and
      accreditation standards in Canada. DESIGN AND METHODS: The review is written
      based on information collected by survey questionnaires, a comprehensive review
      of available websites, and personal communications. RESULTS: Accreditation of
      medical laboratories in Canada is regulated by provincial health authorities. Out
      of the ten provinces of Canada, five have provincial accreditation bodies, while
      in the other five provinces, medical laboratories are accredited by Canadian
      Counsel on Health Service Accreditation (CCHSA). Each of these accreditation
      bodies has developed their own standards, implementing the International
      Organization for Standardization (ISO) documents to variable extent. Canadian
      Coalition for Quality in Laboratory Medicine (CCQLM) has recently been
      incorporated to provide a national structure for harmonizing quality management
      in medical laboratories across Canada. CONCLUSIONS: Although provincially
      regulated, implementation of ISO in accreditation standards and coalition of
      accreditation bodies have been promoting the harmonization of quality regulations
      in Canada.

PMID- 19863916
TI  - Medical laboratory quality and accreditation in Jordan.
AB  - OBJECTIVES: To investigate and describe the current status of quality regulations
      and accreditation standards in the medical laboratories in Jordan. DESIGN AND
      METHODS: Describe the demography of Jordan. Classify the medical laboratories by
      health sectors. Describe the authority bodies in regard to health sectors and
      medical laboratories. Review the current by laws of licensing a medical
      laboratory, quality regulations, and accreditation projects currently active in
      Jordan. RESULTS: Jordan is a developing country in the Middle East with limited
      resources, young population, but special success in education and health sectors.
      Medical laboratory services are being provided by many sectors. In regard to
      licensing to open a private laboratory, regulations are set and applied well.
      Regulations with regard to quality are set, but are not uniformly applied.
      Accreditation is a new concept, a voluntary process, and been granted to few
      laboratories by international accreditation bodies. Two local accreditation
      projects have started licensing to open a private laboratory is well regulated.
      CONCLUSIONS: Quality regulations are set, but not uniformly applied.
      Accreditation is a new concept and needs to be encouraged and improved.

PMID- 19863917
TI  - Standardization of pathology laboratories in Pakistan: problems and prospects.
AB  - A Total Quality Management System with an internationally recognized
      accreditation process is the only guarantee of a reliable pathology service.
      However in a developing country like Pakistan nearly 90% of labs are small and
      without adequate physical and man power infrastructures. A modified plan may have
      to be tailored for them. A two tier system has been formulated. Accreditation
      based on ISO 15189 is to be introduced on voluntary basis. The labs which do not
      qualify for international standardization would be brought into quality net
      through a registration process. All such labs will be initiated into a simplified
      quality management system. Participation in proficiency testing program will be
      mandatory. They will be provided education and training to become eligible for
      accreditation. It is hoped that this simplified system will provide an impetus
      for evolving a workable and comprehensive mechanism through which pathology
      laboratories in the country will be able to offer better and more reliable
      services.

PMID- 19863919
TI  - Implementing a resource management program for accreditation process at the
      medical laboratory.
AB  - OBJECTIVES: To plan for and provide adequate resources to meet the mission and
      goals of a medical laboratory in compliance with the requirements for laboratory
      accreditation by Joint Commission International. DESIGN AND METHODS: The related
      policies and procedures were developed based on standard requirements for
      resource management. RESULTS: Competency assessment provided continuing education
      and performance feedback to laboratory employees. Laboratory areas were designed
      for the efficient and safe performance of laboratory work. A physical environment
      was built up where hazards were controlled and personnel activities were managed
      to reduce the risk of injuries. An Employees Occupational Safety and Health
      Program (EOSHP) was developed to address all types of hazardous materials and
      wastes. Guidelines were defined to verify that the methods would produce accurate
      and reliable results. CONCLUSIONS: An active resource management program will be
      an effective way of assuring that systems are in control and continuous
      improvement is in progress.

PMID- 19863918
TI  - Quality regulations and accreditation standards for clinical chemistry in Turkey.
AB  - OBJECTIVE: The purpose of this paper is to review the current status of
      laboratory quality regulations and accreditation standards in Turkey. DESIGN AND
      METHOD: This paper is written based on the current regulations, information
      collected by available websites and congress proceedings, and personal
      communications. RESULTS: A total of 14 private and one public laboratory have
      been accredited according to ISO 15189 voluntarily. The total number of the JCI
      accredited hospitals is 24. One hospital has been accredited by HQS. A few
      medical laboratories have been accredited according to ISO 17025, whereas a lot
      of them have ISO 9001 certification from Turkish Accreditation Agency, TURKAK.
      There are no comprehensive laboratory standards and/or regulations to maintain a
      mandatory minimum quality of laboratories. External QC is not mandatory and there
      is no national proficiency testing program. It is a requirement to get a license
      to open a laboratory. There are residency programs for clinical chemistry and
      clinical microbiology. The Association of Clinical Biochemists, KBUD, is the
      youngest society in the field of clinical chemistry and is a leader in quality
      and accreditation activities. KBUDEK is an external QC program of KBUD. KBUD has
      organized four national and an international symposiums on quality and
      accreditation in addition to annual congresses and courses. CONCLUSION: The new
      standard and regulation should be designed and applied to all laboratories to
      increase the quality of laboratory service in Turkey. It will be useful if the
      ISO 15189 standard can be incorporated into the national standards and
      regulations.

PMID- 19863920
TI  - ISO 15189 accreditation: Requirements for quality and competence of medical
      laboratories, experience of a laboratory I.
AB  - AIM: Medical laboratories are the key partners in patient safety. Laboratory
      results influence 70% of medical diagnoses. Quality of laboratory service is the
      major factor which directly affects the quality of health care. The clinical
      laboratory as a whole has to provide the best patient care promoting excellence.
      METHODS: International Standard ISO 15189, based upon ISO 17025 and ISO 9001
      standards, provides requirements for competence and quality of medical
      laboratories. Accredited medical laboratories enhance credibility and competency
      of their testing services. Our group of laboratories, one of the leading
      institutions in the area, had previous experience with ISO 9001 and ISO 17025
      Accreditation at non-medical sections. We started to prepared for ISO 15189
      Accreditation at the beginning of 2006 and were certified in March, 2007. We
      spent more than a year to prepare for accreditation. RESULTS: Accreditation
      scopes of our laboratory were as follows: clinical chemistry, hematology,
      immunology, allergology, microbiology, parasitology, molecular biology of
      infection serology and transfusion medicine. The total number of accredited tests
      is 531. We participate in five different PT programs. Inter Laboratory Comparison
      (ILC) protocols are performed with reputable laboratories. 82 different PT
      Program modules, 277 cycles per year for 451 tests and 72 ILC program
      organizations for remaining tests have been performed. Our laboratory also
      organizes a PT program for flow cytometry. 22 laboratories participate in this
      program, 2 cycles per year. Our laboratory has had its own custom made WEB based
      LIS system since 2001. We serve more than 500 customers on a real time basis. Our
      quality management system is also documented and processed electronically,
      Document Management System (DMS), via our intranet. CONCLUSION: Preparatory phase
      for accreditation, data management, external quality control programs, personnel
      related issues before, during and after accreditation process are presented.
      Every laboratory has to concentrate on patient safety issues related to
      laboratory testing and should perform quality improvement projects.

PMID- 19863921
TI  - ISO 15189 accreditation: Requirements for quality and competence of medical
      laboratories, experience of a laboratory II.
AB  - OBJECTIVES: Our laboratory was accredited for 531 tests according to ISO 15189
      standard (ISO 15189:2003 Medical laboratories--Particular requirements for
      quality and competence specifies the quality management system requirements
      particular to medical laboratories) in 2007. An ambitious and young group of
      laboratory personnel has spent efforts with commitment and dedication to complete
      the heavy work of preparation and passed through assessment with success. We
      herewith share our experience of the accreditation, the stages we have been
      through; our solutions to obstacles which we came across during the process.
      DESIGN AND METHODS: Our approaches to topics of environmental conditions,
      document management system (CentroDMS), use of the laboratory information system
      (CentroLIS), corrective/preventive actions and measurement uncertainty are
      summarized in this article. RESULTS: Experience of our laboratory in different
      areas of ISO 15189 accreditation is presented in summary. CONCLUSION:
      Accreditation of medical laboratories increases the quality of the results,
      motivates the laboratory personnel and is beneficial for all interested bodies.
      Continuous improvement and dedicated people are the key elements for continuation
      of the quality assurance in an accredited medical laboratory.

PMID- 19863922
TI  - Joint Commission on International Accreditation workshop: Planning, development
      and provision of laboratory services.
AB  - Throughout the world, the oversight of health care quality is accomplished
      through professionally based accrediting bodies and state regulatory agencies.
      These organizations set standards or define regulations that address important
      organizational functions. The Joint Commission, a private sector United States
      based non-profit organization, is the forerunner and best known among healthcare
      accreditation groups. One of the functions assessed by the standards of the JCI
      Clinical Laboratory Accreditation Program is the planning, development and
      provision of laboratory services. The standards related to this issue address the
      necessary processes that should be in place prior to performing patient testing.

PMID- 19863923
TI  - Implementation of quality control performance criteria and approved guidelines
      for upgrading of clinical chemistry laboratory procedures in Alexandria
      University hospitals.
AB  - The aim of the present work was to assess the quality of work in Clinical
      Pathology Department, Alexandria Main University Hospital, Egypt; as regards the
      pre-analytical and analytical phases of testing; for later accreditation. This
      evaluation was performed using inspection sheets that were designed according to
      the CAP 2006 recommendations. All checklist questions that could not be answered
      "yes" were considered deficiencies and had to be corrected before being
      accredited. The questions were classified into ten groups; each group contained a
      number of questions concerning one of the pre-analytical and analytical
      assessment activities. We ranked our results into 4 categories according to the
      degree of fulfillment. The total number of questions that were answered "no" at
      the start and the end of the study accounted for 64/101 (63.4%) and 34/101
      (33.7%) questions respectively. Most of the deficiencies were detected in the pre
      analytical phase of the testing process; the first two checklists were used for
      the evaluation of this phase. At the start of the study, the degree of
      requirements fulfillment in checklist I and II were 0% and 21.1% respectively. By
      the end of the study the degree of fulfillment became, 85.7% and 63.2%
      respectively. Average number of sample rejection due to different causes was
      evaluated before and after implementing CAP recommendations; these causes include
      haemolysis, clotted serum, quantity not sufficient, and lost samples; the
      percentage of rejected samples before implementing CAP recommendations was 15.8%,
      1.81%, 0.70%, and 0.51% respectively, while after implementing CAP
      recommendations it was 7%, 0.77%, 0.08%, and 0.05%, respectively. We concluded
      that the presence of standardized protocol for the pre-analytical activities had
      improved the quality of samples received by the lab, and we also concluded that
      accreditation allows laboratories to evaluate their performance, their compliance
      with the requirements of the accrediting association, and their ability to
      improve the accuracy of the patient results they provide.

PMID- 19863924
TI  - Implementation of the concept of traceability in laboratory medicine in external
      quality assessment.

PMID- 19863925
TI  - Cardiac biomarkers: establishing reference ranges and standardization of assays
      across laboratories for clinical practice.

PMID- 19863926
TI  - Reference intervals and decision limits for markers of micronutrient status.

PMID- 19863927
TI  - Common reference intervals: the IFCC position.

PMID- 19863928
TI  - Patient safety and privacy in the electronic health information era: medical and
      beyond.

PMID- 19863929
TI  - Efficacy of clinical laboratory: therapeutic TAT, safety, and medical errors.

PMID- 19863930
TI  - Laboratory quality management systems: missions, goals and activities in quality
      assurance.

PMID- 19863931
TI  - Joint Commission International Accreditation for Clinical Laboratories: Monitor,
      analyze and improve.

PMID- 19863932
TI  - ISO 15189 accreditation in medical laboratories: An institutional experience from
      Turkey.

PMID- 19863933
TI  - Accreditation process of a proficiency testing provider according to ILAC G13:
      2000/ISO G43-1: 1999.

PMID- 19863934
TI  - Evaluation of laboratory tests according to quality expectations.

PMID- 19863935
TI  - Quality and accreditation in Arab countries.

PMID- 19863936
TI  - Accreditation of clinical laboratories in the Latin-American region.

PMID- 19863937
TI  - The laboratory accreditation and regulations of clinical laboratory in China.

PMID- 19863938
TI  - Accreditation of medical laboratories in Egypt.

PMID- 19863939
TI  - Laboratory and quality regulations and accreditation standards in Finland.

PMID- 19863940
TI  - Organization and evolution of the regulation and standards in France for the
      clinical laboratories.

PMID- 19863941
TI  - Laboratory quality regulations and accreditation standards in Germany.

PMID- 19863942
TI  - Laboratory quality regulations and accreditation standards in Iran.

PMID- 19863943
TI  - Laboratory quality regulations and accreditation standards in Italy.

PMID- 19863944
TI  - Mexican experience on laboratory accreditation according to ISO 15189:2003.

PMID- 19863945
TI  - Quality management in Syria.

PMID- 19863946
TI  - Clinical implications of the type 1/type 2 balance of helper T cells and P
      glycoprotein function in peripheral T lymphocytes of myasthenia gravis patients.
AB  - Myasthenia gravis is an autoimmune disorder mediated by antibodies against the
      acetylcholine receptors of the skeletal muscles. Imbalances between T helper type
      1 and type 2 cytokine production play a key role in the induction and development
      of several autoimmune diseases. Peripheral T helper type 1 and type 2 cells in 50
      myasthenia gravis patients were estimated by intracellular cytokines. The
      percentage of T helper type 1 cells in CD4(+) cells was higher than that of type
      2 or type 0 cells (P<0.0001). There was a significant correlation between T
      helper type 1/type 2 ratio and the P-glycoprotein function on CD3(+) T cells
      (P=0.008). In the patients treated with prednisolone alone (n=12), there was a
      significant correlation negatively between the percentage of change in the T
      helper type 1/type 2 ratio and the reduction rate of quantitative myasthenia
      gravis scores after 12 months of treatment (P=0.012). In contrast, all of the
      patients treated with prednisolone and calcineurin inhibitor in combination saw
      reductions in the scores. Our data suggest that the T helper type 1/type 2 ratio
      was involved in the disease activity of the patients treated with prednisolone
      alone. On the other hand, the patients treated with prednisolone and calcineurin
      inhibitor in combination had their disease condition improved regardless of the T
      helper type 1 predominance. Therefore, the data suggest that supplemental
      calcineurin inhibitors are effective for the myasthenia gravis patients treated
      with prednisolone alone when their T helper balance shifts toward to type 1.

PMID- 19863948
TI  - Gaze avoidance in social phobia: objective measure and correlates.
AB  - Gaze aversion could be a central component of the physiopathology of social
      phobia. The emotions of the people interacting with a person with social phobia
      seem to model this gaze aversion. Our research consists of testing gaze aversion
      in subjects with social phobia compared to control subjects in different
      emotional faces of men and women using an eye tracker. Twenty-six subjects with
      DSM-IV social phobia were recruited. Twenty-four healthy subjects aged and sex
      matched constituted the control group. We looked at the number of fixations and
      the dwell time in the eyes area on the pictures. The main findings of this
      research are: confirming a significantly lower amount of fixations and dwell time
      in patients with social phobia as a general mean and for the 6 basic emotions
      independently from gender; observing a significant correlation between the
      severity of the phobia and the degree of gaze avoidance. However, no difference
      in gaze avoidance according to subject/picture gender matching was observed.
      These findings confirm and extend some previous results, and suggest that eye
      avoidance is a robust marker of persons with social phobia, which could be used
      as a behavioral phenotype for brain imagery studies on this disorder.

PMID- 19863947
TI  - Increased activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase in the frontal cortex
      and cerebellum of autistic individuals.
AB  - AIMS: Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase are enzymes known to maintain
      intracellular gradients of ions that are essential for signal transduction. The
      aim of this study was to compare the activities of Na(+)/K(+)-ATPase and
      Ca(2+)/Mg(2+)-ATPase in postmortem brain samples from the cerebellum and frontal,
      temporal, parietal, and occipital cortices from autistic and age-matched control
      subjects. MAIN METHODS: The frozen postmortem tissues from different brain
      regions of autistic and control subjects were homogenized. The activities of
      Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase were assessed in the brain homogenates
      by measuring inorganic phosphorus released by the action of Na(+)/K(+)- and
      Ca(2+)/Mg(2+)-dependent hydrolysis of ATP. KEY FINDINGS: In the cerebellum, the
      activities of both Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase were significantly
      increased in the autistic samples compared with their age-matched controls. The
      activity of Na(+)/K(+)-ATPase but not Ca(2+)/Mg(2+)-ATPase was also significantly
      increased in the frontal cortex of the autistic samples as compared to the age
      matched controls. In contrast, in other regions, i.e., the temporal, parietal and
      occipital cortices, the activities of these enzymes were similar in autism and
      control groups. SIGNIFICANCE: The results of this study suggest brain-region
      specific increases in the activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)
      ATPase in autism. Increased activity of these enzymes in the frontal cortex and
      cerebellum may be due to compensatory responses to increased intracellular
      calcium concentration in autism. We suggest that altered activities of these
      enzymes may contribute to abnormal neuronal circuit functioning in autism.

PMID- 19863949
TI  - Concise synthesis of two trisaccharides related to the cytotoxic triterpenoid
      saponin isolated from Pithecellobium lucidum.
AB  - Convergent synthesis of two trisaccharides related to the cytotoxic triterpenoid
      saponin isolated from Pithecellobium lucidum is reported. The trisaccharides are
      synthesized in the form of their propargyl glycosides to leave the scope for
      further glycoconjugate formation through various multi-component reactions. A
      simple protecting group manipulation is followed using commercially available
      monosaccharides, D-glucose, D-xylose, D-fucose and L-rhamnose. H(2)SO(4)
      immobilized on silica is used as the Bronsted acid source for the N
      iodosuccinimide-mediated thioglycoside activation for stereoselective
      glycosylations and proved to be a better choice over traditional Lewis acid
      catalysts such as TMSOTf and TfOH.

PMID- 19863950
TI  - Quaternization of N-aryl chitosan derivatives: synthesis, characterization, and
      antibacterial activity.
AB  - Chemical modification of chitosan by introducing quaternary ammonium moieties
      into the polymer backbone renders excellent antimicrobial activity to the
      adducts. In the present study, we have synthesized 17 derivatives of chitosan
      consisting of a variety of N-aryl substituents bearing either electron-donating
      or electron-withdrawing groups. Selective N-arylation of chitosan was performed
      via Schiff bases formed by the reaction between the 2-amino groups of the
      glucosamine residue of chitosan with aromatic aldehydes under acidic conditions,
      followed by reduction of the Schiff base intermediates with sodium
      cyanoborohydride. Each of the derivatives was further quaternized using N-(3
      chloro-2-hydroxypropyl)trimethylammonium chloride (Quat-188) as the quaternizing
      agent that reacted with either the primary amino or hydroxyl groups of the
      glucosamine residue of chitosan. The resulting quaternized materials were water
      soluble at neutral pH. Minimum inhibitory concentration (MIC) antimicrobial
      studies of these materials were carried out on Escherichia coli (Gram-negative)
      and Staphylococcus aureus (Gram-positive) bacteria in order to explore the impact
      of the extent of N-substitution (ES) on their biological activities. At ES less
      than 10%, the presence of the hydrophobic substituent, such as benzyl and
      thiophenylmethyl, yielded derivatives with lower MIC values than chitosan Quat
      188. Derivatives with higher ES exhibited reduced antibacterial activity due to
      low quaternary ammonium moiety content. At the same degree of quaternization, all
      quaternized N-aryl chitosan derivatives bearing either electron-donating or
      electron-withdrawing substituents did not contribute antibacterial activity
      relative to chitosan Quat-188. Neither the functional group nor its orientation
      impacted the MIC values significantly.

PMID- 19863951
TI  - Studies on the interactions between glycosylated beta3-peptides and the lectin
      Vicia villosa by saturation transfer difference NMR spectroscopy.
AB  - Saturation transfer difference (STD) NMR spectroscopy was used to study the
      interaction of the lectin Vicia villosa (VVLB(4)) with alpha-D-GalNAc
      glycosylated beta(3)-peptides. The data were compared to those obtained with the
      monosaccharides D-Gal, D-GalNAc, and D-Glc as well as with those obtained with
      the Tn antigen alpha-glycopeptide (D-GalNAc-alpha-O-Ser/Thr), molecule naturally
      recognized by V. villosa. Evidence that the lectin also recognizes glycosylated
      beta(3)-peptides and has close contact with both the sugar and amino acid
      moieties was obtained.

PMID- 19863952
TI  - [Diagnostic value of laparoscopy in peritoneal lymphomatosis].

PMID- 19863953
TI  - No association between ambient particulate matter exposure during pregnancy and
      stillbirth risk in the north of England, 1962-1992.
AB  - OBJECTIVES: Research evidence suggests that exposure to ambient air pollutants
      can adversely affect the growth and development of the foetus and infant
      survival. Much less is known regarding the potential for an association between
      black smoke air pollution and stillbirth risk. This potential association was
      examined using data from the historical cohort UK Particulate Matter and
      Perinatal Events Research (PAMPER) study. METHODS: Using data from paper-based
      neonatal records from the two major maternity hospitals in Newcastle upon Tyne
      (UK), a birth record database of all singletons born during 1961-1992 to mothers
      resident in the city was constructed. Weekly black smoke levels were obtained
      from routine data recorded at 20 air pollution monitoring stations over the study
      period. A two-stage statistical modelling strategy was used, incorporating
      temporally and spatially varying covariates to estimate black smoke exposure
      during each trimester and for the whole pregnancy period for each individual
      pregnancy. Conditional logistic regression models, with stratification on year of
      birth, were used to assess potential associations between black smoke exposures
      in pregnancy and stillbirth risk. RESULTS: The PAMPER database consists of 90,537
      births, between 1962 and 1992, with complete gestational age and residential
      address information, of which 812 were stillborn. There was no association
      between black smoke exposures in any trimester or across whole pregnancy and risk
      of stillbirth. Adjustment for potential confounders did not alter these results.
      CONCLUSIONS: While black smoke in pregnancy is likely to be related to other
      pregnancy outcomes, our findings do not suggest that black smoke air pollution
      exposure during pregnancy increases the risk of stillbirth.

PMID- 19863954
TI  - Cholangioscopy and pancreatoscopy (with videos).

PMID- 19863955
TI  - Effect of the BioEnterics intragastric balloon on weight, insulin resistance, and
      liver steatosis in obese patients.
AB  - BACKGROUND: In obese patients, positioning of the BioEnterics intragastric
      balloon (BIB) proved beneficial for weight loss, but the effect of the device on
      ameliorating some components of the metabolic syndrome associated with obesity
      remains uncertain. OBJECTIVE: To evaluate the effectiveness of BIB insertion on
      weight control and amelioration of components of the metabolic syndrome. DESIGN:
      A prospective intervention study performed at baseline, 6 months after BIB
      insertion, and after a mean (standard deviation [SD]) of 21 (3) months (range 14
      26) of follow-up. SETTING: Division of Gastroenterology and Endoscopic Unit,
      "Casa Sollievo della Sofferenza" Hospital. PATIENTS: One hundred thirty obese
      patients with a mean (SD) weight of 118 (24) kg and mean (SD) body mass index
      (BMI) of 43 (8) kg/m(2). INTERVENTIONS: Positioning of BIB. MAIN OUTCOME
      MEASUREMENTS: Anthropometric and laboratory parameters. RESULTS: Overall, the
      mean (SD) weight and BMI decreased by 13.2 (8.2) kg and 5.1 (3.2) kg/m(2),
      respectively, compared with baseline. The mean glycemia, insulinemia, Homeostasis
      Model Assessment index, triglyceridemia, and alanine aminotransferase levels were
      significantly reduced. In the 91 responders (BMI decrease of > or = 3.5 kg/m(2)),
      the mean (SD) weight and BMI decreased by 16.4 (6.3) kg and 6.4 (2.3) kg/m(2),
      respectively, and severe liver steatosis decreased from 52% to 4% (P < .0001). On
      multivariate analysis, severe steatosis and the Homeostasis Model Assessment
      index were predictive of the response to BIB: odds ratios of 6.71 (95% CI, 2.23
      20.19) and 3.18 (95% CI, 1.20-8.42). After a median follow-up of 22 months after
      BIB removal, 50% of responders maintained or continued to lose weight.
      LIMITATIONS: No sham-treated patients were included as comparative controls.
      CONCLUSIONS: Treatment was effective in inducing weight loss, improving liver
      steatosis, and restoring some components of the metabolic syndrome.

PMID- 19863956
TI  - Combined endoscopic and percutaneous drainage of organized pancreatic necrosis.
AB  - BACKGROUND: Severe acute pancreatitis is often complicated by organized necrosis,
      which can lead to abscess formation and clinical deterioration. We sought to
      devise a combined endoscopic and percutaneous approach to drainage of organized
      pancreatic necrosis, with the primary goal of preventing the formation of chronic
      pancreaticocutaneous fistulae, and secondary goals of avoiding the need for
      surgical necrosectomy and reducing endoscopic resource utilization. DESIGN:
      Retrospective review of an institutional review board-approved database. SETTING:
      Single North American tertiary referral center. PATIENTS: Patients with severe
      acute pancreatitis complicated by organized necrosis requiring drainage.
      INTERVENTIONS: CT-guided percutaneous drain, followed immediately by endoscopic
      transenteric drainage. MAIN OUTCOME MEASUREMENTS: Development of chronic
      pancreaticocutaneous fistulae, number of endoscopic procedures requiring follow
      up drainage, need for surgical necrosectomy, procedure-related morbidity, and
      mortality. RESULTS: Fifteen patients (12 males, 3 females; mean age, 58 years)
      underwent combined modality drainage. All procedures were technically successful.
      Immediate complications included fever and hypotension (n = 2); late
      complications included parenchymal infection after drain removal (n = 1). Twenty
      five total endoscopies (4 for drain manipulation) were performed in the cohort
      subsequent to the initial drainage. After a median duration of follow-up of 189
      days, percutaneous drains were removed in all 13 patients in whom this was
      attempted; no patients had development of chronic pancreaticocutaneous fistulae.
      There were no deaths, and no patients required surgery. LIMITATIONS: Highly
      selected patient population, lack of comparison group, single-center experience.
      CONCLUSIONS: In some highly selected patients with infected or symptomatic
      organized pancreatic necrosis, combined modality drainage results in favorable
      clinical outcomes with low associated, procedure-related morbidity.
      Pancreaticocutaneous fistulae and surgical necrosectomy were avoided with minimal
      endoscopic resource utilization.

PMID- 19863957
TI  - Capsule endoscopy in patients with Crohn's disease: diagnostic yield and safety.
AB  - BACKGROUND: Capsule endoscopy (CE) is increasingly used in patients with
      suspected or known Crohn's disease (CD). OBJECTIVE: To determine the diagnostic
      yield of CE and the distribution of small-bowel (SB) lesions in symptomatic
      patients with known CD. DESIGN AND SETTING: Retrospective review of CE procedures
      performed in patients with CD between 2001 and 2005 in a tertiary care center.
      PATIENTS: One hundred thirty-four patients with an established diagnosis of CD
      and symptoms suggestive of active disease. INTERVENTIONS: Swallowing the capsule.
      MAIN OUTCOME MEASUREMENTS: Diagnostic yield of CE and distribution of SB lesions
      in patients with CD. RESULTS: One hundred forty-six CE procedures were performed
      on 134 CD patients. Fifty-two (39%) of 134 patients had CE findings diagnostic of
      active CD (> 3 ulcerations), and 17 (13%) had findings suggestive of active CD (<
      or = 3 ulcerations). Fifty-seven (42%) patients had normal findings, and 6% had
      normal but incomplete studies. The distribution of SB lesions was 32% in the
      duodenum, 53% in the jejunum, 67% in the proximal ileum, and 85% in the distal
      ileum. CE was comparable to ileoscopy in detecting ileal ulcerations (55% vs
      48%), but superior to SB follow-through in detecting CD lesions in the SB
      (incremental yield of 32%; 95% CI, 9%-54%; P = .0017). LIMITATIONS: Retrospective
      study from a single center. CONCLUSIONS: CE identified SB lesions in
      approximately half of symptomatic CD patients. Large-scale prospective studies
      are needed to evaluate whether positive CE findings may affect disease outcomes.

PMID- 19863958
TI  - Fulminant amebic colitis mimicking pseudomembranous colitis.

PMID- 19863959
TI  - Correlates of self-care behaviors for managing hypertension among Korean
      Americans: a questionnaire survey.
AB  - BACKGROUND: While self-care behaviors have been documented as one of the main
      determinant of hypertension control, studies investigating correlates of self
      care behaviors have been rare regarding hypertension among minority population.
      OBJECTIVES: The purpose of this study was to examine factors associated with self
      care behaviors for hypertension using a community sample of Korean Americans.
      DESIGN: A descriptive cross-sectional design. SETTINGS: Community setting in the
      Baltimore-Washington metropolitan area. PARTICIPANTS: The sample included 445
      middle-aged (40-64 years of age) Korean Americans with hypertension (systolic BP
      > or = 140 and/or diastolic BP > or = 90 mmHg; or taking antihypertensive
      medication). METHODS: Guided by Social Cognitive Theory, a variety of personal
      (age, gender, marital status, employment status, years in U.S., duration of
      hypertension, hypertension knowledge, hypertension belief, and hypertension
      control self-efficacy) and environmental (social support) factors were examined
      in relation to hypertension self-care behaviors, including medication-taking,
      exercise, diet, and weight control. RESULTS: The model explained 18.0% of the
      total variance in self-care scores. Hierarchical multiple regression revealed
      that personal factors contributed significantly to the explanatory model, whereas
      social support did not add much. Examination of individual regression
      coefficients showed that Korean Americans who were older, who had longer duration
      of hypertension, and who had higher hypertension control self-efficacy were more
      likely to have higher self-care scores. CONCLUSIONS: Hypertension control self
      efficacy emerged as the most significant contributing factor to hypertension self
      care. Future intervention programs should focus on improving hypertension control
      self-efficacy as a modifiable personal factor.

PMID- 19863960
TI  - Compressive strain rate sensitivity of ballistic gelatin.
AB  - Gelatin is a popular tissue simulant used in biomedical applications. The
      uniaxial compressive stress-strain response of gelatin was determined at a range
      of strain rates. In the quasistatic regime, gelatin strength remained relatively
      constant. With increase in loading rate, the compressive strength increased from
      3kPa at a strain rate of around 0.0013/s to 6MPa at a strain rate of around
      3200/s. This dramatic increase in strength of gelatin at high rates is attributed
      to its shear-thickening behavior and is argued on the basis of hydrocluster
      formation mechanism and differences in internal energy dissipation mechanism
      under static and dynamic loading.

PMID- 19863961
TI  - Direct contribution of axial impact compressive load to anterior tibial load
      during simulated ski landing impact.
AB  - Anterior tibial loading is a major factor involved in the anterior cruciate
      ligament (ACL) injury mechanism during ski impact landing. We sought to
      investigate the direct contribution of axial impact compressive load to anterior
      tibial load during simulated ski landing impact of intact knee joints without
      quadriceps activation. Twelve porcine knee specimens were procured. Four
      specimens were used as non-impact control while the remaining eight were mounted
      onto a material-testing system at 70 degrees flexion and subjected to simulated
      landing impact, which was successively repeated with incremental actuator
      displacement. Four specimens from the impacted group underwent pre-impact MRI for
      tibial plateau angle measurements while the other four were subjected to
      histology and microCT for cartilage morphology and volume assessment. The tibial
      plateau angles ranged from 29.4 to 38.8 degrees . There was a moderate linear
      relationship (Y=0.16X; R(2)=0.64; p<0.001) between peak axial impact compressive
      load (Y) and peak anterior tibial load (X). The anterior and posterior regions in
      the impacted group sustained surface cartilage fraying, superficial clefts and
      tidemark disruption, compared to the control group. MicroCT scans displayed
      visible cartilage deformation for both anterior and posterior regions in the
      impacted group. Due to the tibial plateau angle, increased axial impact
      compressive load can directly elevate anterior tibial load and hence contribute
      to ACL failure during simulated landing impact. Axial impact compressive load
      resulted in shear cartilage damage along anterior-posterior tibial plateau
      regions, due to its contribution to anterior tibial loading. This mechanism plays
      an important role in elevating ACL stress and cartilage deformation during impact
      landing.

PMID- 19863962
TI  - Body position determines propulsive forces in accelerated running.
AB  - Rapid accelerations during running are crucial for the performance in a lot of
      sports. While high propulsive forces are beneficial to forward acceleration,
      vertical forces have to be small to attain high stride frequencies. However,
      propulsive and vertical force components cannot be altered independently, because
      the resultant force vector affects the angular momentum of the body. Therefore we
      hypothesized that propulsive forces in accelerated running mainly depend on body
      position regardless of performance level. In our cross-sectional study 28 male
      and 13 female physical education students performed submaximal and maximal
      accelerations. Ground reaction forces and whole body kinematics were recorded.
      Higher accelerations were generated by lower, but more forward oriented forces.
      The orientation of the maximum force vector strongly correlated with the forward
      lean of the body at toe-off (r=0.93,p<or=0.001). All subjects demonstrated
      similar propulsive forces at equal body positions. This indicates an external
      constraint of propulsive force application by the mechanical requirement of
      running to maintain a stable body posture. Faster subjects utilized a more
      posterior foot plant or a longer ground contact time. Both strategies facilitated
      greater forward leans of the body which finally resulted in greater propulsive
      forces. Consequently, maximizing forward propulsion requires optimal, not maximal
      force application.

PMID- 19863963
TI  - In-line preconcentration of oxidized and reduced glutathione in capillary zone
      electrophoresis using transient isotachophoresis under strong counter
      electroosmotic flow.
AB  - Transient isotachophoresis (tITP) can improve the sensitivity of capillary
      electrophoresis (CE). In general, it was carried out under the condition of
      suppressed electroosmotic flow (EOF). However, some special conditions, such as
      extreme low pH background electrolyte and coating were needed to achieve the
      requirements of suppressed EOF. In this work, an approach of tITP under the
      strong counter-EOF in open system (counter-EOF-tITP) is presented for the rapid
      and sensitive preconcentrating the reduced glutathione (GSH) and the oxidized
      glutathione (GSSG) without modifying the capillary and the commercial CE
      instrument. The parameters of the experimental system, such as the concentration
      of leading electrolyte, the injected amount of terminating electrolyte and the
      injected pressure of sample were investigated in detail to understand the
      mechanism of counter-EOF-tITP. The sensitivity enhancement factors were of 320
      for GSH and 280 for GSSG. In addition, the detection limit of 23.4 and 18.0
      microg L(-1) for GSH and GSSG was achieved, respectively. The method's
      applicability was demonstrated by determining GSH and GSSG in tomato and human
      serum.

PMID- 19863964
TI  - Preparation and evaluation of a macroporous molecularly imprinted hybrid silica
      monolithic column for recognition of proteins by high performance liquid
      chromatography.
AB  - A novel type of macroporous molecularly imprinted hybrid silica monolithic column
      was first developed for recognition of proteins. The macroporous silica-based
      monolithic skeleton was synthesized in a 4.6mm i.d. stainless steel column by a
      mild sol-gel process with methyltrimethoxysilane (MTMS) as a sole precursor, and
      then vinyl groups were introduced onto the surface of the silica skeleton by
      chemical modification of gamma-methacryloxypropyltrimethoxysilane (gamma-MAPS).
      Subsequently, the molecularly imprinted polymer (MIP) coating was copolymerized
      and anchored onto the surface of the silica monolith. Bovine serum albumin (BSA)
      and lysozyme (Lyz), which differ greatly in molecular size, isoelectric point,
      and charge, were representatively selected for imprinted templates to evaluate
      recognition property of the hybrid silica-based MIP monolith. Some important
      factors, such as template-monomer molar ratio, total monomer concentration and
      crosslinking density, were systematically investigated. Under the optimum
      conditions, the obtained hybrid silica-based MIP monolith showed higher binding
      affinity for template than its corresponding non-imprinted (NIP) monolith. The
      imprinted factor (IF) for BSA and Lyz reached 9.07 and 6.52, respectively.
      Moreover, the hybrid silica-based MIP monolith displayed favorable binding
      characteristics for template over competitive protein. Compared with the
      imprinted silica beads for stationary phase and in situ organic polymer-based
      hydrogel MIP monolith, the hybrid silica MIP monolith exhibited higher
      recognition, stability and lifetime.

PMID- 19863965
TI  - Development and validation of an automated monitoring system for oxygenated
      volatile organic compounds and nitrile compounds in ambient air.
AB  - Few studies were conducted on oxygenated volatile organic compounds (OVOC)
      because of problems encountered during the sampling/analyzing steps induced by
      water in sampled air. Consequently, there is a lack of knowledge of their spatial
      and temporal trends and their origins in ambient air. In this study, an analyzer
      consisted of a thermal desorber (TD) interfaced with a gas chromatograph (GC) and
      a flame ionization detector (FID) was developed for online measurements of 18
      OVOC in ambient air including 4 alcohols, 6 aldehydes, 3 ketones, 3 ethers, 2
      esters and 4 nitriles. The main difficulty was to overcome the humidity effect
      without loss of compounds. Water amount in the sampled air was reduced by the
      trap composition (two hydrophobic graphitized carbons-Carbopack B:Carbopack X),
      the trap temperature (held at 12.5 degrees C), by diluting (50:50) the sample
      with dry air before the preconcentration step and a trap purge with helium.
      Humidity management allowed the use of a polar CP-Lowox column in order to
      separate the polar compounds from the hydrocarbon/aromatic matrix. The safe
      sampling volume for the dual-sorbent trap 75 mg Carbopack X:5mg Carbopack B was
      found to 405 mL for ethanol by analyzing a standard mixture at a relative
      humidity of 80%. Detection limits ranging from 10 ppt for ETBE to 90 ppt for
      ethanol were obtained for 18 compounds for a sampling volume of 405 mL. Good
      repeatabilities were obtained at two levels of concentration (relative standard
      deviation <5%). The calibration (ranging from 0.5 to 10 ppb) was set up at three
      different levels of relative humidity to test the humidity effect on the response
      coefficients. Results showed that the response coefficients of all compounds were
      less affected by humidity except for those of ethanol and acetonitrile (decrease
      respectively of 30% and 20%). The target compounds analysis shows good
      reproducibility with response coefficient variability of less then 10% of the
      mean initial value of calibration for all the compounds. Hourly ambient air
      measurements were conducted in an urban site in order to test this method. On the
      basis of these measurements, ethanol, acetone and acetaldehyde have shown the
      highest concentration levels with an average of 2.10, 1.75 and 1.37 ppb
      respectively. The daily evolution of some OVOC, namely ethanol and acetaldehyde,
      was attributed to emissions from motor vehicles while acetone has a different
      temporal evolution that can be probably associated with remote sources.

PMID- 19863966
TI  - "Click dipeptide": a novel stationary phase applied in two-dimensional liquid
      chromatography.
AB  - 2D-HPLC is an important technique for the separation of complex samples.
      Developing new types of stationary phases is of great interest to construct 2D-LC
      systems with high orthogonality. In this study, a novel stationary phase-Click
      dipeptide (l-phenylglycine dipeptide) was prepared by immobilization of alpha
      azido l-phenylglycine dipeptide on alkyne-silica via click chemistry. In the
      preparation of this new material, an efficient, inexpensive and shelf-stable
      diazo transfer reagent (imidazole-1-sulfonyl azide hydrochloride) was utilized to
      transfer the amino group of l-phenylglycine to corresponding azido group under
      mild conditions. The Click dipeptide thus prepared was confirmed by FT-IR, solid
      state CP/MAS (13)C NMR and elemental analysis. The Click dipeptide packing showed
      high orthogonality with C18, which reached 63.5%. An off-line 2D-RP/RPLC system
      was developed to analyze a traditional Chinese medicine (TCM)-Rheum Palmatum L.
      The results showed high orthogonality between Click dipeptide and C18 as well as
      great separating power in the practical separation of complex samples.

PMID- 19863967
TI  - Extending the use of "Inverted Chirality Columns Approach" for enantiomeric
      excess determination in absence of reference samples: Application to a water
      soluble camptothecin derivative.
AB  - The aim of the present study was to extend the use of the "Inverted Chirality
      Columns Approach (ICCA)" previously developed for the identification and
      quantitation of the trace enantiomer in highly enriched samples of the
      camptothecin (CPT) family of drugs to a novel water-soluble CPT derivative,
      namely namitecan (ST1968), currently undergoing phase I clinical trials as
      anticancer agent. Namitecan, identified from a series of hydrophilic 7
      oxyiminomethyl derivatives, contains a free terminal amino group, which
      traditionally hampers the analysis under normal-phase HPLC conditions.
      Nevertheless, commercially available Pirkle-type chiral stationary phases (CSPs)
      available in both the enantiomeric forms (i.e., having the same bound selector
      with opposite configuration) mainly operate under normal-phase HPLC conditions.
      For this reason, namitecan was pre-column N-protected with isocyanates A-D and
      their sulfur analogues E-H to reduce its polarity by converting the amino group
      into a fragment compatible with the chiral recognition mechanism (i.e., ureido
      and thioureido groups). Once the optimal columns system and derivatizing agents
      were selected, an original enantioselective HPLC-MS/MS technique was developed on
      the Whelk-O1 CSPs.

PMID- 19863968
TI  - Adrenal cortisol secretion capacity in children and adolescents with new-onset,
      mild Crohn's disease.
AB  - OBJECTIVES: To evaluate the integrity of the hypothalamic-pituitary-adrenal axis
      in active Crohn's disease (CD) among children and adolescents. STUDY DESIGN: We
      retrieved data on patients with CD who participated in a prospective study where
      budesonide treatment was evaluated. Basal and adrenocorticotropic hormone and
      corticotropin-stimulated cortisol levels in 52 children and adolescents with CD
      were compared with levels obtained in 52 age-matched control subjects.
      Correlations of cortisol levels with pediatric CD activity index and C-reactive
      protein (CRP) as an inflammatory marker were also assessed. RESULTS: Both basal
      and stimulated cortisol levels in CD were significantly higher than in control
      subjects: 364 +/- 173 versus 290 +/- 122 nmol/L (P = .029) and 865 +/- 236 versus
      738 +/- 148 nmol/L (P < or = .001), respectively. Cortisol levels were correlated
      with CRP but not with pediatric CD activity index. Unlike in the control group,
      stimulated cortisol levels in patients with CD were not correlated with basal
      levels but rather with CRP (positive correlation) and age at diagnosis (negative
      correlation). CONCLUSIONS: Contrary to previous reports suggesting that
      dysregulation of the hypothalamic-pituitary-adrenal axis is implicated in the
      susceptibility to and severity of CD and other chronic inflammatory diseases, we
      demonstrated an adequate response of this axis in pediatric CD, in proportion to
      the inflammation severity.

PMID- 19863969
TI  - Metabolic risk varies according to waist circumference measurement site in
      overweight boys and girls.
AB  - OBJECTIVES: To compare waist circumference (WC) values measured at 4 commonly
      recommended sites and examine the relationships between WC sites and markers of
      metabolic risk in a sample of overweight boys and girls referred for weight
      management. STUDY DESIGN: Overweight (mean body mass index percentile, 98.7; SD,
      1.0) children and adolescents (n = 73; 41 girls, 32 boys; mean age, 12.5 years;
      SD, 2.6 years) had WC measured at 4 sites: iliac crest (WC1), narrowest waist
      (WC2), midpoint between the floating rib and iliac crest (WC3), and umbilicus
      (WC4). Height, weight, fasting insulin level, glucose level, cholesterol level,
      and systolic and diastolic blood pressure were also measured. RESULTS: Overall,
      WC1 (108.5 cm; SD, 16.3 cm) was greater than WC2 (97.4 cm; SD, 13.6 cm; P <
      .003), and WC2 was smaller than WC3 (104.3 cm; SD, 15.3 cm; P = .02) and WC4
      (108.7 cm; SD, 16.2 cm; P < .0003). With logistic regression, WC2 and WC3 were
      revealed to be more consistently associated with metabolic syndrome by using 3
      different definitions. CONCLUSION: In our sample, we observed differences in 4
      commonly recommended WC measurement sites and found that all sites were not
      equivalently associated with metabolic risk. Our findings provide preliminary
      support suggesting that WC measured at the narrowest waist and midpoint between
      the floating rib and iliac crest may represent the measurement sites most closely
      associated with metabolic risk in overweight boys and girls.

PMID- 19863970
TI  - Successful intra-arterial thrombolysis beyond the accepted 6-hour time window in
      two young patients.
AB  - Two young women with ischemic stroke successfully underwent intra-arterial
      thrombolysis (IAT) 10 and 11h, respectively after stroke onset. A 23-year-old
      (case 1) and a 22-year-old woman (case 2) who developed severe neurological
      deficits (NIHSS 20 and 13, respectively) were presented to our hospital 9h after
      onset of the symptoms. In case 1 a CT angiography (CTA) revealed an occlusion of
      the left middle cerebral artery (MCA) and in case 2 CTA showed a large embolus at
      the left carotid bifurcation, almost entirely occluding the internal carotid
      artery. We decided to apply IAT beyond the generally accepted 6-hour time window.
      Case 1 was treated with 2mg rtPA administered locally in the occluded MCA
      followed by 70 mg rtPA (1 mg/min) and case 2 was treated with 100,000 IU
      urokinase in the left common carotid artery followed by 200,000 IU during 2h and
      10mg abciximab. In case 1 IAT resulted in complete recanalisation of the MCA
      within 3h and complete resolution of symptoms in the following six weeks. In case
      2 IAT resulted in an initial 50% reduction of the thrombus. After nine days CTA
      showed complete lysis and the patient had completely recovered. Both patients
      suffered from Anti-Phospholipid-Syndrome. The results show that IAT may be
      beneficial to young patients with a severe stroke, even beyond the 6-hour time
      window.

PMID- 19863971
TI  - Electrophysiological evidence of cerebellar fiber system involvement in the
      Miller Fisher syndrome.
AB  - BACKGROUND: In the Miller Fisher syndrome (MFS), ataxia may be due involvement of
      Ia afferents and the cerebellum. Transcranial magnetic stimulation (TMS) over the
      cerebellum is known to interfere transiently with normal function. METHODS: In
      this study, we utilized a previously described TMS protocol over the cerebellum
      in combination with ballistic movements to investigate cerebellar dysfunction in
      MFS patients. RESULTS: The agonist (biceps) reaction time in MFS patients during
      a motor cancellation task was not significantly reduced during the initial TMS
      study. However, during the repeat TMS study, significant reduction was seen for
      all patients, in tandem with clinical recovery. There was significant correlation
      between anti-GQ1b IgG titers and change in agonist reaction time between the
      initial and repeat TMS studies. CONCLUSIONS: TMS likely affected horizontally
      orientated parallel fibers in the cerebellar molecular layer. During disease
      onset, antibody binding may have interfered with facilitation of reaction time
      during motor cancellation tasks seen in normal subjects. Normalization of
      reaction time facilitation corresponded to resolution of antibody-mediated
      interference in the molecular layer. Our study has provided evidence suggesting
      parallel fiber involvement in MFS, and suggested a role of anti-GQ1b IgG antibody
      in these changes.

PMID- 19863972
TI  - [Guidelines for the use of bisphosphonates in multiple myeloma: Recommendations
      of the expert committee of the Spanish Myeloma Group from the PETHEMA group].

PMID- 19863973
TI  - [Resurgence of mumps in the vaccine era. Factors involved in an outbreak in
      Navarre, Spain, 2006-2007].
AB  - BACKGROUND AND OBJECTIVE: We analysed a mumps outbreak that occurred in Navarre
      between August 2006 and December 2007, in which vaccinated persons were widely
      affected. PATIENTS AND METHODS: Reports of mumps cases were completed by
      searching primary, emergency and hospital records and laboratory reports. Factors
      that could affect the occurrence of cases were analysed by birth cohort. RESULTS:
      A total of 2866 mumps cases were detected (attack rate 4.7/1000), with 61% of
      cases in men and a peak incidence at age 19 (inter-quartile range 16-25 years).
      14% of cases were confirmed by laboratory: 59 by virus isolation, 14 by PCR and
      333 by IgM. The G1 genotype was identified in 7 cases. 21% of cases had been born
      before 1980 (pre-vaccine cohorts), and 0.2% had not yet reached the vaccination
      age (15 months). In the cohorts born between 1980 and 2000 (with the opportunity
      for vaccination), 94.5% of cases had received at least one dose and 88.3%, two
      doses. 31% of cases occurred in cohorts vaccinated with a first (1995-1997) or
      second (1986-1988) dose of the Rubini strain. There was also a record of 772
      cases who had received two doses of the Jeryl Lynn strain. CONCLUSIONS: This
      widespread outbreak is explained by the concurrence of various factors. The
      current vaccine has substantially reduced the incidence of mumps, but appears
      unable to totally eliminate virus circulation.

PMID- 19863974
TI  - [Safety and tolerance of beta-blocker treatment in elderly patients with heart
      failure. BETANIC study].
AB  - BACKGROUND AND OBJECTIVE: Prescription of beta-blockers (BB) in elderly patients
      with heart failure (HF) is very low, and it probably owes to an excessive concern
      about the risk of adverse reactions. The objective of our study was to determine
      the safety and tolerance of BB in elderly patients with HF in an Internal
      Medicine clinical practice. MATERIAL AND METHODS: This observational prospective
      study of clinical practice included 119 patients older than 70 years with HF
      evaluated in 10 Internal Medicine services. Patients must have started treatment
      with BB (carvedilol or bisoprolol) within the last month. After 6 months of
      follow-up, the percentage of patients on BB, the dose achieved and the causes of
      withdrawal were analyzed. RESULTS: At the end of the study, 100 patients (84%)
      were on BB treatment. There were 3 deaths (2.5%), none related to BB use, and 6
      losses to follow-up (5%). The treatment was stopped in 10 patients (8.4%).
      Maximum dose was achieved in 38.7% of the patients. Adverse reactions responsible
      for treatment withdrawal were: symptomatic hypotension (3 cases; 2.5%);
      asymptomatic hypotension (1 case; 0.8%); heart failure (2 cases; 1.7%);
      bradycardia (2 cases; 1.7%); bronchospasm (1 case; 0.8%); and unknown cause (1
      case; 0.8%). CONCLUSIONS: BB are excellently tolerated in elderly patients with
      HF treated in an Internal Medicine setting.

PMID- 19863975
TI  - [The dilemma of medical evaluation in non professional sport in children and
      adolescents].

PMID- 19863976
TI  - Between plant and diurnal variation in quantities and ratios of volatile
      compounds emitted by Vicia faba plants.
AB  - Ratios of volatile phytochemicals potentially offer a means for insects to
      recognise their host-plant species. However, for this to occur ratios of
      volatiles would need to be sufficiently consistent between plants and over time
      to constitute a host-characteristic cue. In this context we collected headspace
      samples from Vicia faba plants to determine how consistent ratios of key volatile
      phytochemicals used in host location by one of its insect pests, the black bean
      aphid, Aphis fabae, were. These were (E)-2-hexenal, (Z)-3-hexen-1-ol, 1-hexanol,
      benzaldehyde, 6-methyl-5-hepten-2-one, octanal, (Z)-3-hexen-1-yl acetate, (R)
      linalool, methyl salicylate, decanal, undecanal, (E)-caryophyllene, (E)-beta
      farnesene, (S)-germacrene D, and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene,
      which had previously been found to be electrophysiologically and behaviourally
      active to A. fabae. Although the quantities of volatiles produced by V. faba
      showed large between plant and diurnal variation, correlations between quantities
      of compounds indicated that the ratios of certain pairs of volatiles were very
      consistent. This suggests that there is a host-characteristic cue available to A.
      fabae in the form of ratios of volatiles.

PMID- 19863977
TI  - Acylated triterpene saponins from the roots of Securidaca longepedunculata.
AB  - Four triterpene saponins, 3-O-beta-D-glucopyranosylpresenegenin 28-O-beta-D
      apiofuranosyl-(1-->3)-beta-d-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]
      alpha-L-rhamnopyranosyl-(1-->2)-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-beta-D
      fucopyranosyl ester, 3-O-beta-D-glucopyranosylpresenegenin 28-O-beta-D
      apiofuranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta-D-apiofuranosyl-(1-->3)]
      alpha-L-rhamnopyranosyl-(1-->2)-[(6-O-acetyl)-beta-D-glucopyranosyl-(1-->3)]-{4-O
      [(E)-3,4,5-trimethoxycinnamoyl]}-beta-D-fucopyranosyl ester, 3-O-beta-D
      glucopyranosylpresenegenin 28-O-beta-D-apiofuranosyl-(1-->3)-beta-D-xylopyranosyl
      (1-->4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D
      galactopyranosyl-(1-->3)]-{4-O-[(E)-3,4,5-trimethoxycinnamoyl]}-beta-D
      fucopyranosyl ester, and 3-O-beta-D-glucopyranosylpresenegenin 28-O-beta-D
      apiofuranosyl-(1-->3)-[alpha-L-arabinopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-
      >4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-{4-O-[(E)
      3,4,5-trimethoxycinnamoyl]}-beta-D-fucopyranosyl ester, were isolated from the
      roots of Securidaca longepedunculata, together with three known compounds. Their
      structures were established mainly by 2D NMR techniques and mass spectrometry.

PMID- 19863978
TI  - Aspects on evolution of fungal beta-lactam biosynthesis gene clusters and
      recruitment of trans-acting factors.
AB  - Penicillins and cephalosporins are beta-lactam antibiotics. The formation of
      hydrophobic penicillins has been reported in fungi only, notably Penicillium
      chrysogenum and Aspergillus (Emericella) nidulans, whereas the hydrophilic
      cephalosporins are produced by both fungi, e.g., Acremonium chrysogenum
      (cephalosporin C), and bacteria. The producing bacteria include Gram-negatives
      and Gram-positives, e.g., Streptomyces clavuligerus (cephamycin C) and Lysobacter
      lactamgenus (cephabacins), respectively. The evolutionary origin of beta-lactam
      biosynthesis genes has been the subject of discussion for many years, and two
      main hypotheses have been proposed: (i) horizontal gene transfer (HGT) from
      bacteria to fungi or (ii) vertical decent. There are strong arguments in favour
      of HGT, e.g., unlike most other fungal genes, beta-lactam biosynthesis genes are
      clustered and some of these genes lack introns. In contrast to S. clavuligerus,
      all regulators of fungal beta-lactam biosynthesis genes represent wide-domain
      regulators that are not part of the gene cluster. If bacterial regulators were co
      transferred with the gene cluster from bacteria to fungi, most likely they would
      have been non-functional in eukaryotes and lost during evolution. Recently, the
      penicillin biosynthesis gene aatB was discovered, which is not part of the
      penicillin biosynthesis gene cluster and is even located on a different
      chromosome. The aatB gene is regulated by the same regulators AnCF and AnBH1 as
      the penicillin biosynthesis gene aatA (penDE). Data suggest that aatA and aatB
      are paralogues derived by duplication of a common ancestor gene. This data
      supports a model in which part of the beta-lactam biosynthesis gene cluster was
      transferred to some fungi, i.e., the acvA and ipnA gene without a regulatory
      gene. We propose that during the assembly of aatA and acvA-ipnA into a single
      gene cluster, recruitment of transcriptional regulators occurred along with
      acquisition of the duplicated aatA ancestor gene and its cis-acting sites.

PMID- 19863979
TI  - Endophytic fungal strains of Fusarium solani, from Apodytes dimidiata E. Mey. ex
      Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9
      methoxycamptothecin.
AB  - Camptothecin and 10-hydroxycamptothecin are two important precursors for the
      synthesis of the clinically useful anticancer drugs, topotecan and irinotecan. In
      recent years, efforts have been made to identify novel plant and endophytic
      fungal sources of camptothecin and 10-hydroxycamptothecin. In this study we have
      isolated endophytic fungi strains from Apodytes dimidiata (Icacinaceae), a medium
      sized tree from the Western Ghats, India. The fungi were identified as Fusarium
      solani using both ITS rDNA sequencing and spore morphology. Two strains, MTCC
      9667 and MTCC 9668 were isolated, both of which produced camptothecin and 9
      methoxycamptothecin in their mycelia; one of the strains, MTCC 9668 also produced
      10-hydroxycamptothecin, though in small amounts. The yields of camptothecin in
      MTCC 9667 and MTCC 9668 were 37 and 53 microg/100g, respectively, after 4 days of
      incubation in broth culture. The yields of 10-hydroxycamptothecin and 9
      methoxycamptothecin in MTCC 9668 were 8.2 and 44.9 microg/100g, respectively.
      Further research in optimizing the culture conditions of these fungal strains
      might permit their application for the production of camptothecin and 10
      hydroxycamptothecin.

PMID- 19863980
TI  - Cervical screening: Perceptions and barriers to uptake among Somali women in
      Camden.
AB  - OBJECTIVES: To explore barriers to, and ways to improve, uptake of cervical
      screening among Somali women in Camden, London. STUDY DESIGN: A qualitative
      research study using focus group discussions and in-depth interviews. METHODS: A
      qualitative study (comprising seven focus groups and eight in-depth interviews)
      was conducted with 50 first-generation Somali women aged 25-64 years. Both the
      groups and the interviews explored participants' understanding of the purpose of
      cervical screening, and the various risk factors for cervical cancer, as well as
      their opinions on barriers to screening and suggestions for overcoming those
      barriers. RESULTS: Knowledge about the purpose of cervical screening was limited
      among Somali women. There was also a lack of understanding of risk factors for
      cervical cancer, and many of the women held fatalistic attitudes, associated with
      the idea of 'God's will', about this cancer and other aspects of health. Another
      culturally specific barrier was embarrassment associated with female
      circumcision, i.e. female genital mutilation. Other barriers suggested by the
      participants were: lack of knowledge about the need for cervical screening,
      practical problems such as appointment times and childcare needs, language
      difficulties, fear of the test and negative past experiences. Possible solutions
      suggested by the participants included the provision of education and information
      about cervical screening in the Somali language by Somali community workers. They
      also suggested that healthcare staff should be trained about Somali culture,
      particularly regarding female circumcision, and that general practitioners should
      more proactively encourage Somali women to attend screening. CONCLUSIONS:
      Language difficulties and specific cultural issues are key barriers to first
      generation Somali women attending cervical screening. Providing education and
      information orally, as well as improving access to a more culturally appropriate
      screening service, could lead to improved uptake among this group.

PMID- 19863981
TI  - [Current state of noninvasive vascular diagnosis in Spain].
AB  - OBJECTIVE: Noninvasive vascular diagnosis has become routine in radiology
      departments in Spain. This article aims to communicate the results of a survey
      sent to a large number of Spanish hospitals to obtain information about the
      following aspects of noninvasive vascular diagnosis: who performs it and how, in
      what conditions it is performed, what problems there are in relation to these
      techniques, and what the training is like. MATERIAL AND METHODS: In October 2008,
      we sent a questionnaire to 93 hospitals with training programs in diagnostic
      imaging and to 45 hospitals without training programs. The questionnaire
      solicited information about the hospital and its technological and human
      resources, the organization of the diagnostic imaging department, the performance
      of different noninvasive vascular examinations, and the respondents' opinions
      about problems related to these techniques and about the state of training
      programs. RESULTS: A total of 43 (46%) of the 93 teaching hospitals and 9 (20%)
      of the non-teaching hospitals responded to the survey. This article uses multiple
      tables and figures to communicate the responses obtained in the survey.
      CONCLUSIONS: The results of the survey provide a view of the current state of
      noninvasive vascular diagnosis in teaching hospitals in Spain in concrete
      figures. We hope that these data will stimulate diagnostic imaging departments to
      protect these techniques and to actively promote training in noninvasive vascular
      diagnosis.

PMID- 19863982
TI  - [Percutaneous radiofrequency ablation of benign bone tumors: osteoid osteoma,
      osteoblastoma, and chondroblastoma].
AB  - We report our experience in the computed tomography (CT)-guided percutaneous
      radiofrequency ablation of more than 100 benign bone tumors in the last eight
      years. We affirm that this should be the technique of choice in the vast majority
      of osteoid osteomas; it can also be applied as a definitive treatment in many
      cases of osteoblastomas or chondroblastomas as well as in less common benign bone
      tumors. CT-guided percutaneous radiofrequency ablation has proven highly
      efficacious and has resulted in very few complications; thus, patients tend to
      recover very quickly.

PMID- 19863983
TI  - [Aneurysmal bone cysts of the mandible].
AB  - The aneurysmal bone cyst is a rare, expansive, osteolytic, pseudocystic lesion
      with an unknown etiology. It usually affects long bones and the spine. Two to 5 %
      of cases have mandibular localization (between 75 and 100 % present on the
      mandible) accounting for 1 % of all mandibular cysts. Less than 200 cases have
      been reported in English and French literature.

PMID- 19863984
TI  - Numerous studies have considered opportunity costs of operating time.

PMID- 19863985
TI  - Malignant fibrous histiocytoma of the greater omentum.

PMID- 19863986
TI  - Bridge venoplasty: a new technique to simplify venous outflow reconstruction in
      living donor domino liver transplantation.

PMID- 19863987
TI  - Noninvasive electromechanical wave imaging and conduction-relevant velocity
      estimation in vivo.
AB  - Electromechanical wave imaging is a novel technique for the noninvasive mapping
      of conduction waves in the left ventricle through the combination of ECG gating,
      high frame rate ultrasound imaging and radio-frequency (RF)-based displacement
      estimation techniques. In this paper, we describe this new technique and
      characterize the origin and velocity of the wave under distinct pacing schemes.
      First, in vivo imaging (30 MHz) was performed on anesthetized, wild-type mice
      (n=12) at high frame rates in order to take advantage of the transient
      electromechanical coupling occurring in the myocardium. The RF signal acquisition
      in a long-axis echocardiographic view was gated between consecutive R-wave peaks
      of the mouse electrocardiogram (ECG) and yielded an ultra-high RF frame rate of
      8000 frames/s (fps). The ultrasound RF signals in each frame were digitized at
      160 MHz. Axial, frame-to-frame displacements were estimated using 1D cross
      correlation (window size of 240 microm, overlap of 90%). Three pacing protocols
      were sequentially applied in each mouse: (1) sinus rhythm (SR), (2) right-atrial
      (RA) pacing and (3) right-ventricular (RV) pacing. Pacing was performed using an
      eight-electrode catheter placed into the right side of the heart with the
      capability of pacing from any adjacent bipole. During a cardiac cycle, several
      waves were depicted on the electromechanical wave images that propagated
      transmurally and/or from base to apex, or apex to base, depending on the type of
      pacing and the cardiac phase. Through comparison between the cine-loops and their
      corresponding ECG obtained at different pacing protocols, we were able to
      identify and separate the electrically induced, or contraction, waves from the
      hemodynamic (or, blood-wall coupling) waves. In all cases, the contraction wave
      was best observed along the posterior wall starting at the S-wave of the ECG,
      which occurs after Purkinje fiber, and during myocardial, activation. The
      contraction wave was identified based on the fact that it changed direction only
      when the pacing origin changed, i.e., it propagated from the apex to the base at
      SR and RA pacing and from base to apex at RV pacing. This reversal in the wave
      propagation direction was found to be consistent in all mice scanned and the wave
      velocity values fell within the previously reported conduction wave range with
      statistically significant differences between SR/RA pacing (0.85+/-0.22 m/s and
      0.84+/-0.20 m/s, respectively) and RV pacing (-0.52+/-0.31 m/s; p<0.0001). This
      study thus shows that imaging the electromechanical function of the heart
      noninvasively is feasible. It may therefore constitute a unique noninvasive
      method for conduction wave mapping of the entire left ventricle. Such a
      technology can be extended to 3D mapping and/or used for early detection of
      dyssynchrony, arrhythmias, left-bundle branch block, or other conduction
      abnormalities as well as diagnosis and treatment thereof.

PMID- 19863988
TI  - Removal of micropollutants and reduction of biological activity in a full scale
      reclamation plant using ozonation and activated carbon filtration.
AB  - Pharmaceutical compounds are found in secondary treated effluents up to microg L(
      1) levels and therefore discharged into surface waters. Since the long term
      effects of these compounds on the environment and human health are, to date,
      largely unknown, implementation of advanced treatment of wastewaters is envisaged
      to reduce their discharge. This is of particular relevance where surface waters
      are used as drinking water sources and when considering indirect potable reuse.
      This study aimed at assessing the removal of organic micropollutants and the
      concurrent reduction of their biological activity in a full scale reclamation
      plant treating secondary effluent. The treatment consists of 6 stages:
      denitrification, pre-ozonation, coagulation/flocculation/dissolved air flotation
      and filtration (DAFF), main ozonation, activated carbon filtration and final
      ozonation for disinfection. For that purpose, representative 24-hour composite
      samples were collected after each stage. The occurrence of 85 compounds was
      monitored by LC/MS-MS. A battery of 6 bioassays was also used as a complementary
      tool to evaluate non-specific toxicity and 5 specific toxic modes of action.
      Results show that, among the 54 micropollutants quantified in the influent water,
      50 were removed to below their limit of quantification representing more than 90%
      of concentration reduction. Biological activity was reduced, depending on the
      specific response that was assessed, from a minimum of 62% (AhR response) to more
      than 99% (estrogenicity). The key processes responsible for the plant's
      performances were the coagulation/flocculation/DAFF, main ozonation and activated
      carbon filtration. The effect of these 3 processes varied from one compound or
      bioassay to another but their combination was almost totally responsible for the
      overall observed reduction. Bioassays yielded complementary information, e.g.
      estrogenic compounds were not detected in the secondary effluent by chemical
      analysis, but the samples had an estrogenic effect. The main ozonation formed
      oxidation by-products of the organic micropollutants but decreased the level of
      non-specific toxicity and other specific toxic modes of action, demonstrating
      that the mixture of oxidation by-products was less potent than the mixture of the
      parent compounds for the considered effects.

PMID- 19863989
TI  - Development of solar-driven electrochemical and photocatalytic water treatment
      system using a boron-doped diamond electrode and TiO2 photocatalyst.
AB  - A high-performance, environmentally friendly water treatment system was
      developed. The system consists mainly of an electrochemical and a photocatalytic
      oxidation unit, with a boron-doped diamond (BDD) electrode and TiO(2)
      photocatalyst, respectively. All electric power for the mechanical systems and
      the electrolysis was able to be provided by photovoltaic cells. Thus, this system
      is totally driven by solar energy. The treatment ability of the electrolysis and
      photocatalysis units was investigated by phenol degradation kinetics. An observed
      rate constant of 5.1 x 10(-3)dm(3)cm(-2)h(-1) was calculated by pseudo-first
      order kinetic analysis for the electrolysis, and a Langmuir-Hinshelwood rate
      constant of 5.6 microM(-1)min(-1) was calculated by kinetic analysis of the
      photocatalysis. According to previous reports, these values are sufficient for
      the mineralization of phenol. In a treatment test of river water samples, large
      amounts of chemical and biological contaminants were totally wet-incinerated by
      the system. This system could provide 12L/day of drinking water from the Tama
      River using only solar energy. Therefore, this system may be useful for supplying
      drinking water during a disaster.

PMID- 19863990
TI  - Seasonal and inter-annual variability of DNA integrity in mussels Mytilus
      galloprovincialis: a possible role for natural fluctuations of trace metal
      concentrations and oxidative biomarkers.
AB  - The DNA strand fragmentation as analyzed by the Comet assay is a common biomarker
      widely used to assess the genotoxic potential of chemical pollutants in marine
      organisms. However, basal levels of DNA strand breaks can be influenced also by
      factors unrelated to chemical exposure, and a better knowledge on the natural
      variability of such response would thus be important to discriminate the effects
      of anthropogenic activities. In this respect, the aim of the present work was to
      characterize the fluctuations of DNA strand breaks in mussels, Mytilus
      galloprovincialis, seasonally sampled over a 3 year period from a reference site
      along the Adriatic coast. Parameters reflecting DNA integrity exhibited
      significant seasonal changes in mussels haemocytes, with considerable differences
      between various sampling years. Comparing such results with those previously
      obtained on the natural fluctuations of trace metal concentrations and oxidative
      stress biomarkers in mussels tissues, significant correlations were obtained
      between DNA strand breaks with levels of Ba, Cd, Cu, Hg, Ni, Se, activity of
      catalase and content of malondialdehyde. Although mechanisms remain to be
      demonstrated, the overall results of this work suggest the potential role of
      natural prooxidant factors in affecting the baseline levels of DNA integrity in
      mussels, and confirm that natural variability of such responses should be
      carefully considered when monitoring the impact of genotoxins in marine
      ecosystems.

PMID- 19863992
TI  - Contamination levels of mercury in the muscle of female and male spiny dogfishes
      (Squalus acanthias) caught off the coast of Japan.
AB  - We analyzed the total mercury (T-Hg) and stable isotopes of (13)C and (15)N in
      the muscle of spiny dogfish (Squalus acanthias) caught off the coast of Japan.
      The average body length of the female spiny dogfish sampled (94.9+/-20.2 cm, 50.5
      131.0 cm, n=40) was significantly larger than that of the males sampled (77.8+/
      10.8 cm, 55.5-94.0 cm, n=35), although the ages of the samples were unknown. The
      T-Hg concentration in the muscle samples rapidly increased after maturity in the
      females (larger than about 120 cm) and males (larger than about 90 cm), followed
      by a continued gradual increase. Contamination level of T-Hg in female muscle
      samples (0.387+/-0.378 microg(wet g)(-1), n=40) was slightly higher than that in
      male muscle samples (0.316+/-0.202 microg(wet g)(-1), n=35), probably due to the
      greater longevity of females. In contrast, the contamination level of T-Hg in
      females smaller than 94.0 cm in length (0.204+/-0.098 microg(wet g)(-1), n=20)
      was slightly lower than that in the males, probably due to the faster growth rate
      of females. Although the partial differential(13)C and partial differential(15)N
      values in the muscle samples increased with an increase in body length, there
      were no significant differences between the females (-17.2+/-0.4 per thousand and
      12.4+/-0.9 per thousand, respectively) and males (-17.3+/-0.4 per thousand and
      12.4+/-0.8 per thousand, respectively). A positive correlation was found between
      partial differential(13)C and partial differential(15)N values, suggesting
      trophic enrichment due to the growth.

PMID- 19863991
TI  - Reproductive performance in East Greenland polar bears (Ursus maritimus) may be
      affected by organohalogen contaminants as shown by physiologically-based
      pharmacokinetic (PBPK) modelling.
AB  - Polar bears (Ursus maritimus) feed mainly on ringed seal (Phoca hispida) and
      consume large quantities of blubber and consequently have one of the highest
      tissue concentrations of organohalogen contaminants (OHCs) worldwide. In East
      Greenland, studies of OHC time trends and organ system health effects, including
      reproductive, were conducted during 1990-2006. However, it has been difficult to
      determine the nature of the effects induced by OHC exposures on wild caught polar
      bears using body burden data and associated changes in reproductive organs and
      systems. We therefore conducted a risk quotient (RQ) evaluation to more
      quantitatively evaluate the effect risk on reproduction (embryotoxicity and
      teratogenicity) based on the critical body residue (CBR) concept and using a
      physiologically-based pharmacokinetic (PBPK) model. We applied modelling
      approaches to PCBs, p,p'-DDE, dieldrin, oxychlordane, HCHs, HCB, PBDEs and PFOS
      in East Greenland polar bears based on known OHC pharmacokinetics and dynamics in
      laboratory rats (Rattus rattus). The results showed that subcutaneous adipose
      tissue concentrations of dieldrin (range: 79-1271 ng g(-1) lw) and PCBs (range:
      4128-53,923 ng g(-1) lw) reported in bears in the year 1990 were in the range to
      elicit possible adverse health effects on reproduction in polar bears in East
      Greenland (all RQs > or = 1). Similar results were found for PCBs (range: 1928
      17,376 ng g(-1) lw) and PFOS (range: 104-2840 ng g(-1) ww) in the year 2000 and
      for dieldrin (range: 43-640 ng g(-1) lw), PCBs (range: 3491-13,243 ng g(-1) lw)
      and PFOS (range: 1332-6160 ng g(-1) ww) in the year 2006. The concentrations of
      oxychlordane, DDTs, HCB and HCHs in polar bears resulted in RQs<1 and thus appear
      less likely to be linked to reproductive effects. Furthermore, sumRQs above 1
      suggested risk for OHC additive effects. Thus, previous suggestions of possible
      adverse health effects in polar bears correlated to OHC exposure are supported by
      the present study. This study also indicates that PBPK models may be a supportive
      tool in the evaluation of possible OHC-mediated health effects for Arctic
      wildlife.

PMID- 19863993
TI  - Occurrence and fate of rosuvastatin, rosuvastatin lactone, and atorvastatin in
      Canadian sewage and surface water samples.
AB  - Rosuvastatin (RST) and atorvastatin (ATO) are prescription drugs and members in
      the statin family used for the treatment of elevated cholesterol levels. A method
      using solid-phase extraction and liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) for the determination of ATO, RST and its metabolite rosuvastatin
      lactone (RSTL) in sewage and surface water samples has been developed. In the
      influent and effluent samples collected from 11 sewage treatment plants located
      in Ontario, Canada, ATO, RST, and RSTL were detected in all samples with median
      concentrations of 166 ng L(-1) (influent) and 77 ng L(-1) (effluent) for ATO, 448
      ng L(-1) (influent) and 324 ng L(-1) (effluent) for RST, as well as 158 ng L(-1)
      (influent) and 41 ng L(-1) (effluent) for RSTL. Due to the inter-conversion
      between RST and RSTL, the total concentration of RST and RSTL in a sewage sample
      should be reported. The median removal rate by wastewater treatment was 66% for
      ATO and 22% for RST and RSTL combined. These statins were quite persistent in
      sewage. After a storage period of 21 and 62 days, there was only a slight
      decrease in ATO concentration and no change in the total RST concentrations.
      These three compounds were also detected in a number of surface water samples at
      low ng L(-1) concentrations. This is the first reported occurrence and fate of
      RST and RSTL in the Canadian aquatic environment.

PMID- 19863994
TI  - Discussion of "Polybrominated diphenyl ethers in aircraft cabins--a source of
      human exposure?" by Anna Christiansson et al. [Chemosphere 73(10) (2008) 1654
      1660].
AB  - This paper presents new data on the levels of polybrominated diphenyl ethers
      (PBDEs) in American airline workers. This pilot study did not find elevated total
      PBDEs in the blood of nine flight attendants and one aircraft pilot who have
      worked in airplanes for at least the past 5 years. These findings are not
      consistent with the findings of elevated blood levels of PBDEs from the 2008
      Christiansson et al. publication "Polybrominated diphenyl ethers in aircraft
      cabins - A source of human exposure?" We agree that more research needs to be
      done on larger, more representative samples of airline workers to better
      characterize exposure of airline workers and other frequent flyers to PBDEs.

PMID- 19863995
TI  - Mutagenic activities of a chlorination by-product of butamifos, its structural
      isomer, and their related compounds.
AB  - The mutagenic activities of 5-methyl-2-nitrophenol (5M2NP), a chlorination by
      product of butamifos, its structural isomer 2-methyl-5-nitrophenol (2M5NP), and
      related compounds were evaluated by the Ames assay. The mutagenic activities of
      5M2NP and 2M5NP were negative or not particularly high. However, those of their
      chlorinated derivatives were increased in Salmonella typhimurium strain TA100 and
      the overproducer strains YG1026, and YG1029 in the absence and/or presence of a
      rat liver metabolic activation system (S9 mix), particularly for YG1029. The
      mutagenic activities of 6-chloro-2-methyl-5-nitrophenol (6C2M5NP) in YG1029 in
      the absence and presence of S9 mix were 70000 and 110000 revertants mg(-1),
      respectively. When nitro functions of 6C2M5NP and 4-chloro-5-methyl-2-nitrophenol
      (4C5M2NP) were reduced to amino functions, their mutagenic activities were
      markedly decreased. The mutagenic activities of 5M2NP and 4C5M2NP were lower than
      those of 2M5NP and 6C2M5NP, respectively. Thus, it was shown that substituent
      position is a key factor for the mutagenic activities of methylnitrophenols
      (MNPs) and related compounds. The mutagenic activities of the extracts of 2M5NP
      in chlorination increased early during the reaction time and then decreased. The
      main chlorination by-product contributing to the mutagenic activities of the
      extracts of 2M5NP in chlorination was 6C2M5NP. The results of chlorination of
      2M5NP suggested that MNPs were present as their dichlorinated derivatives or
      further chlorination by-products in drinking water.

PMID- 19863996
TI  - Liquid chromatographic enantioseparation of the brominated flame retardant 2,3
      dibromopropyl-2,4,6-tribromophenyl ether (DPTE) and enantiomer fractions in seal
      blubber.
AB  - Enantioselective analyses of the chiral brominated flame retardant 2,3
      dibromopropyl-2,4,6-tribromophenyl ether (DPTE) are the focus of this work. High
      performance liquid chromatography (HPLC) equipped with a column that had a chiral
      stationary phase consisting of a modified cellulose derivative allowed for the
      fractionation of the enantiomers of DPTE. The enantiomeric excess was 98.2% for
      enantiomer 1 and 99% for enantiomer 2. Polarimetric measurements verified that
      the first eluting enantiomer originated from (-)-DPTE and the second peak
      originated from (+)-DPTE. Two gas chromatographic columns allowed for the direct
      enantioresolution of DPTE. The elution order of DPTE enantiomers was the same as
      observed in the chiral HPLC system ((-)-DPTE before (+)-DPTE). The best
      enantioseparation was achieved on a Chirasil-DEX CB column, which was used to
      analyze the enantiomer fractions of DPTE in blubber and brain samples of hooded
      seals (Cystophora cristata) and harp seals (Phoca groenlandica) from the Barents
      and Greenland Seas. Analyses were carried out by means of gas
      chromatography/electron capture negative ion mass spectrometry operated in the
      selected ion monitoring (GC/ECNI-MS-SIM) mode. In both matrices, only minute
      deviations from the racemate were observed (maximum +/-3% excess of (-)-DPTE).
      However, the samples from the Barents Sea were either racemic or showed a slight
      excess of (+)-DPTE (up to 2.5%), whereas all samples from the Greenland Sea
      contained a slight excess (up to 4%) of (-)-DPTE.

PMID- 19863997
TI  - Into Eurasia: a geometric morphometric re-assessment of the Upper Cave
      (Zhoukoudian) specimens.
AB  - Since the discovery of the human remains from the Upper Cave of Zhoukoudian in
      the 1930s there has been speculation over their affinities. In particular, the
      degree to which the three adult crania exhibit recent East Asian morphology, as
      well as their degree of within-group variability, has long been debated. Several
      early researchers described a resemblance to East Asian populations, but these
      findings have been for the most part rejected by more recent metric and non
      metric analyses. Nevertheless, the Upper Cave specimens have not been classified
      conclusively into any recent modern human population to which they have been
      compared, and classification results differ for each cranium. Here, the question
      of the affinities of Upper Cave 101 and 103, the two better-preserved crania, is
      examined from the perspective of the Late Pleistocene human fossil record using
      the methodology of 3-D geometric morphometrics. The degree of morphological
      variation between the two specimens is also evaluated within the context of
      recent population variability. Neurocranial and facial morphology are analyzed
      separately so as to maximize comparative samples. Results show a morphological
      resemblance of the Upper Cave material to Upper Paleolithic Europeans. It is
      proposed that the Upper Cave specimens retain important aspects of modern human
      ancestral morphology, and possibly share a recent common ancestral population
      with Upper Paleolithic Europeans, in accordance with the Single Origin model of
      modern human origins.

PMID- 19863998
TI  - Robust stochastic fuzzy possibilistic programming for environmental decision
      making under uncertainty.
AB  - Nonpoint source (NPS) water pollution is one of serious environmental issues,
      especially within an agricultural system. This study aims to propose a robust
      chance-constrained fuzzy possibilistic programming (RCFPP) model for water
      quality management within an agricultural system, where solutions for farming
      area, manure/fertilizer application amount, and livestock husbandry size under
      different scenarios are obtained and interpreted. Through improving upon the
      existing fuzzy possibilistic programming, fuzzy robust programming and chance
      constrained programming approaches, the RCFPP can effectively reflect the complex
      system features under uncertainty, where implications of water quality/quantity
      restrictions for achieving regional economic development objectives are studied.
      By delimiting the uncertain decision space through dimensional enlargement of the
      original fuzzy constraints, the RCFPP enhances the robustness of the optimization
      processes and resulting solutions. The results of the case study indicate that
      useful information can be obtained through the proposed RCFPP model for providing
      feasible decision schemes for different agricultural activities under different
      scenarios (combinations of different p-necessity and p(i) levels). A p-necessity
      level represents the certainty or necessity degree of the imprecise objective
      function, while a p(i) level means the probabilities at which the constraints
      will be violated. A desire to acquire high agricultural income would decrease the
      certainty degree of the event that maximization of the objective be satisfied,
      and potentially violate water management standards; willingness to accept low
      agricultural income will run into the risk of potential system failure. The
      decision variables under combined p-necessity and p(i) levels were useful for the
      decision makers to justify and/or adjust the decision schemes for the
      agricultural activities through incorporation of their implicit knowledge. The
      results also suggest that this developed approach is applicable to many practical
      problems where fuzzy and probabilistic distribution information simultaneously
      exist.

PMID- 19863999
TI  - Possible interaction between a rodenticide treatment and a pathogen in common
      vole (Microtus arvalis) during a population peak.
AB  - A common vole (Microtus arvalis) population peak in Northern Spain in 2007 was
      treated with large scale application of chlorophacinone, an anticoagulant
      rodenticide of the indandione family. Voles found dead and trapped alive were
      collected in treated and untreated areas. Residues of chlorophacinone were
      analyzed in liver of voles by HPLC-UV. Also, the presence of the pathogen
      Francisella tularensis was analyzed by PCR in samples of vole spleen.
      Chlorophacinone (82-3800 ng/g; wet weight liver) was only detected in voles found
      dead in treated areas (55.5%). The prevalence of F. tularensis in voles found
      dead in treated areas was also particularly high (66.7%). Moreover,
      chlorophacinone levels were lower in voles that were PCR-positive for F.
      tularensis (geometric mean [95% CI], 418 [143-1219] ng/g) than in those that were
      PCR-negative (1084 [581-2121] ng/g). Interactions between pathogens and
      rodenticides might be considered to reduce the doses used in baits or to avoid
      the use of the more toxic 2nd generation anticoagulant rodenticides.

PMID- 19864000
TI  - A critical appraisal of the value of lymph node dissection at nephroureterectomy
      for upper tract urothelial carcinoma.
AB  - OBJECTIVES: To perform a population-based analysis of the potential staging or
      prognostic value (or both) of lymph node dissection (LND) in patients without
      nodal metastases vs no LND. In several previous reports, LND in patients with
      upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy (NU) was
      associated with better survival relative to no LND (pN(x)), even in the absence
      of pathologically confirmed nodal metastases (pN(0)). METHODS: Within the
      surveillance, epidemiology, and end results database, we identified 2824 patients
      treated with NU for UTUC between 1988 and 2004. CSM rates after NU were
      graphically explored using Kaplan-Meier plots. Univariable and multivariable Cox
      regression models tested the effect of N(0) vs N(x) stage on CSM, after adjusting
      for T stage, tumor grade, age, gender, primary tumor location, type, and year of
      surgery. RESULTS: The CSM-free survival rate at 5 years after NU was 81.2% and
      77.8% respectively for pN(0) and pN(x) patients. In univariable analyses pN(x) vs
      pN(0) status was not associated with worse survival (HR: 1.19; P = .09). After
      adjustment for all covariates, pN(x) vs pN(0) status still failed to achieve
      independent predictor status (HR: 0.99; P = .9). CONCLUSIONS: We found no
      survival benefit related to the performance of LND in pN(0) patients, relative to
      pN(x) patients. Lack of standardized criteria for patients' selection for LND and
      for pathological lymph node specimen evaluation represents some of the
      explanation for the observed discrepancy between the current finding and previous
      findings.

PMID- 19864001
TI  - Therapeutic management of de novo urological malignancy in renal transplant
      recipients: the experience of the French Department of Urology and Kidney
      Transplantation from Bordeaux.
AB  - OBJECTIVES: To determine and analyze the incidence, prognosis, and therapeutic
      strategy of de novo urological malignancies in a series of renal transplant
      recipients (RTRs). METHODS: A retrospective study of 1350 recipients between
      January 1998 and January 2008 was carried out; we reviewed the data of 42 de novo
      urological malignancies in 39 recipients. RESULTS: There were 21 cases of
      prostate cancer, 13 cases of renal cell carcinoma in 10 patients, 3 cases of
      renal graft tumors, and 5 cases of transitional cell carcinoma of the bladder.
      The overall incidence of urological neoplasms was 3.1%. The mean age of cancer
      diagnosis was 60 +/- 8.3 years. The mean duration of dialysis before cancer
      diagnosis was 35 +/- 37.5 months. About 92% of patients underwent hemodialysis
      (34/39) and the remaining underwent peritoneal dialysis (5/39). All the 39
      recipients received cadaveric kidneys. The mean follow-up period for this study
      was 33 +/- 34.4 months (range 2-160 months). There appears to be a greater risk
      of urological neoplasm in RTRs. Prostate cancer and renal carcinoma can be
      treated in a similar manner than in general population with encouraging
      oncological results and low morbidity. However, the transitional cell carcinoma
      of the bladder remains particularly aggressive requiring optimal treatment
      despite the morbidity concerning the intravesical therapy. CONCLUSIONS: We can
      apply the standard medical and surgical treatment in RTRs, with encouraging
      oncological results if a strict screening program is established and followed by
      the patients.

PMID- 19864002
TI  - Construction of neourethra using flipped anterior bladder wall tube in a
      prepubertal girl with complete disruption of urethra.
AB  - A rare case of urethral construction using flipped anterior bladder wall tube in
      an 8-year-old girl with complete disruption of the urethra and vagina
      accompanying pelvic fracture was reported. Following a split of the pubic
      symphysis, the vagina was reconstructed with end-to-end anastomosis. The
      neourethra was constructed tubularizing and flipping anterior bladder wall flap
      caudally to proximal site of the original urethra after fascial sling procedure.
      After catheter removal, this girl has been continent and voided normally. In
      conclusion, flipped anterior bladder wall tube technique for urethral
      construction is suitable in prepubertal girls with complete disruption of the
      urethra.

PMID- 19864003
TI  - The importance of serum prostate-specific antigen testing frequency in assessing
      biochemical and clinical failure after prostate cancer treatment.
AB  - OBJECTIVES: To assess the relationship between prostate-specific antigen (PSA)
      testing frequency and biochemical failure (bF) and clinical failure (cF).
      METHODS: The records of 5616 patients with low-, intermediate-, or high-risk
      prostate cancer treated (brachytherapy, external beam radiotherapy, or surgery)
      between 1996 and 2007 were reviewed. Factors influencing bF and cF were recorded
      including age, initial PSA, androgen deprivation, race, clinical stage, biopsy
      Gleason score, and the frequency of follow-up PSA testing. Univariate and
      multivariate analyses were performed to assess the effect of these factors on bF
      and cF. Sensitivity and specificity were calculated to determine the optimal
      frequency of PSA testing. RESULTS: The median follow-up is 45 months. The median
      number of PSA tests per year before the occurrence of bF and cF is 1.9 for both
      endpoints. The multivariate analysis of factors significantly associated with bF
      and cF demonstrate that PSA frequency, initial PSA, clinical stage, and biopsy
      Gleason score are independently predictive of outcome. PSA testing achieves the
      best sensitivity and specificity when 2 PSA tests are drawn per year for both bF
      (sensitivity = 66.3%, specificity = 58.0%) and cF (sensitivity = 75.1%,
      specificity = 60.3%). CONCLUSIONS: The frequency of PSA testing is strongly
      associated with the detection of bF and cF. Because it is a variable that can be
      controlled, PSA testing frequency should be standardized to minimize spurious
      conclusions from studies with bF and cF endpoints. The sensitivity and
      specificity can be optimized by obtaining 2 PSA tests per year.

PMID- 19864004
TI  - Effect of sustained hydrostatic pressure on rat bladder smooth muscle cell
      function.
AB  - OBJECTIVES: To test a hypothesis that bladder smooth muscle cells (BSMCs) shift
      their phenotype from contractile to synthetic in response to elevated hydrostatic
      pressure. Although mechanical stimuli are needed for development of the bladder,
      the exact mechanisms for this process are poorly understood. METHODS: Rat BSMCs
      were exposed to 7.5 cm H(2)O of hydrostatic pressure in custom-made columns to a
      maximum of 48 hours. After exposure to pressure, the smooth muscle cells were
      fixed, stained, and imaged to quantify cell morphology and proliferation.
      Additionally, Western blotting was used to quantify extracellular signal
      regulated kinase (ERK(1/2)) activation as well as phenotype marker proteins,
      alpha-smooth muscle actin, and SM-22. RESULTS: Compared with the control, BSMCs
      exposed to hydrostatic pressure exhibited a more spread morphology after 4 hours
      and the expression of activated ERK(1/2) was a maximum of two-fold at 1.5-3
      hours. Moreover, cell density of BSMCs exposed to hydrostatic pressure exhibited
      an increase after 48 hours when compared with their respective controls. In
      contrast, alpha-smooth muscle actin and SM-22 expression was similar in the
      control and in cells exposed to hydrostatic pressure for 48 hours. CONCLUSIONS:
      The morphologic and proliferative changes of BSMC in response to hydrostatic
      pressure possibly indicate a phenotypic shift from contractile to synthetic.
      Moreover, the activation of ERK(1/2) intracellular signaling pathway may
      represent a potential mechanism for the pressure-induced BSMC proliferation. The
      comparable levels of contractile proteins observed in both control and pressure
      group BSMCs suggest that not all the phenotype markers are regulated
      concomitantly by a single stimulus.

PMID- 19864005
TI  - Behavioral and urological evaluation of a testicular pain model.
AB  - OBJECTIVES: To develop an animal model of testicular pain to examine the
      hypothesis that neural crosstalk between testicular nociceptors and bladder
      reflex pathways may underlie bladder overactivity. In chronic pelvic pain
      disorders, neural crosstalk is thought to underlie referred pain and functional
      interaction in pelvic organs, and patients with chronic prostatitis/chronic
      pelvic pain syndrome (CP/CPPS) suffer from pain in multiple organs, including the
      testes and perineum, as well as increased urinary frequency. METHODS: In male
      Wistar rats, acetic acid was injected into the testes, and behaviors and bladder
      functions with conscious cystometry were examined. The effects of indomethacin
      and capsaicin pretreatment on both behaviors and bladder functional changes
      induced by acetic acid injection were examined. The weight of the testes and
      bladder after the testicular injection were measured. RESULTS: Injection of
      acetic acid (1% and 3%) induced pain behaviors and bladder overactivity
      proportional to the concentration. Indomethacin reduced, and capsaicin
      pretreatment almost completely abolished, both pain behavior and bladder
      overactivity induced by acetic acid injection. Administration of acetic acid
      increased testis weight and blanched the tissue, but no apparent changes were
      observed in the bladder. CONCLUSIONS: Injection of dilute acetic acid into the
      testes produces a reproducible testicular pain model involving testicular
      inflammation and activation of primary afferent C fibers and suggests a neural
      pathway for interaction between testicular pain and bladder overactivity. This
      study may provide a simple method to evaluate testicular pain, related bladder
      overactivity, and insight into the pathophysiology of bladder overactivity in
      patients with CP/CPPS.

PMID- 19864007
TI  - ITGB2 mutation combined with deleted ring 21 chromosome in a child with leukocyte
      adhesion deficiency.

PMID- 19864008
TI  - Involvement of sirtuin 1 in airway inflammation and hyperresponsiveness of
      allergic airway disease.
AB  - BACKGROUND: Bronchial asthma is a chronic inflammatory disorder of the airways
      characterized by increased expression of multiple inflammatory genes. Acetylation
      of histones by histone acetyltransferases is associated with increased gene
      transcription, whereas hypoacetylation induced by histone deacetylases is
      associated with suppression of gene expression. Sirtuin 1 (SIRT1) is a member of
      the silent information regulator 2 family that belongs to class III histone
      deacetylase. OBJECTIVE: This study aimed to investigate the role of SIRT1 and the
      related molecular mechanisms in the pathogenesis of allergic airway disease.
      METHODS: By using a murine model of ovalbumin (OVA)-induced allergic airway
      disease and murine tracheal epithelial cells, this study investigated the
      involvement of SIRT1 and its signaling networks in allergic airway inflammation
      and hyperresponsiveness. RESULTS: In this study with mice after inhalation of
      OVA, the increased levels of SIRT1, hypoxia-inducible factor 1alpha (HIF-1alpha),
      and vascular endothelial growth factor protein in the lungs after OVA inhalation
      were decreased substantially by the administration of a SIRT1 inhibitor,
      sirtinol. We also showed that the administration of sirtinol reduced
      significantly the increased numbers of inflammatory cells of the airways; airway
      hyperresponsiveness; increased levels of IL-4, IL-5, and IL-13; and increased
      vascular permeability in the lungs after OVA inhalation. In addition, we have
      found that inhibition of SIRT1 reduced OVA-induced upregulation of HIF-1alpha in
      airway epithelial cells. CONCLUSIONS: These results indicate that inhibition of
      SIRT1 might attenuate antigen-induced airway inflammation and hyperresponsiveness
      through the modulation of vascular endothelial growth factor expression mediated
      by HIF-1alpha in mice.

PMID- 19864009
TI  - Counterregulation of beta(2)-adrenoceptor function in human mast cells by stem
      cell factor.
AB  - BACKGROUND: Mast cells contribute to the pathophysiology of asthma with the
      sustained release of both preformed and newly generated mediators in response to
      allergens and other diverse stimuli. Stem cell factor (SCF) is the key human mast
      cell growth factor, but also primes mast cells for mediator release. SCF
      expression is markedly increased in asthmatic airways. Short-acting beta(2)
      adrenoceptor drugs such as albuterol inhibit human lung mast cell (HLMC)
      degranulation in vitro in the absence of SCF, but their effect in the presence of
      SCF is not known. OBJECTIVE: The aim of this study was to elucidate the effects
      of albuterol on HLMC function in the presence of SCF. METHODS: Mediator release
      and K(Ca)3.1 ion channel activity were analyzed in purified HLMC. Intracellular
      signalling and beta(2)-adrenoceptor phosphorylation and internalization were
      analyzed in the HMC-1 human mast cell line. RESULTS: beta(2)-Adrenoceptor agonist
      dependent inhibition of K(Ca)3.1 ion channels and HLMC mediator release was
      markedly attenuated in the presence of SCF. Remarkably, albuterol actually
      potentiated IgE-induced histamine release in a dose-dependent manner when both
      SCF and IgE were present. These effects were related to the SCF-dependent
      phosphorylation of Tyr350 on the beta(2)-adrenoceptor with immediate uncoupling
      of the receptor followed by receptor internalization. CONCLUSION: The potentially
      beneficial effects of beta(2)-adrenoceptor agonists in asthmatic airways may be
      blunted as a result of the high concentrations of SCF present.

PMID- 19864010
TI  - How allergic are "allergic shiners"?

PMID- 19864011
TI  - Glycation of a food allergen by the Maillard reaction enhances its T-cell
      immunogenicity: role of macrophage scavenger receptor class A type I and II.
AB  - BACKGROUND: The Maillard reaction occurs between reducing sugars and proteins
      during thermal processing of foods. It produces chemically glycated proteins
      termed advanced glycation end products (AGEs). The glycation structures of AGEs
      are suggested to function as pathogenesis-related immune epitopes in food
      allergy. OBJECTIVE: This study aimed at defining the T-cell immunogenicity of
      food AGEs by using ovalbumin (OVA) as a model allergen. METHODS: AGE-OVA was
      prepared by means of thermal processing of OVA in the presence of glucose.
      Activation of OVA-specific CD4(+) T cells by AGE-OVA was evaluated in cocultures
      with bone marrow-derived murine myeloid dendritic cells (mDCs) as antigen
      presenting cells. The uptake mechanisms of mDCs for AGE-OVA were investigated by
      using inhibitors of putative cell-surface receptors for AGEs, as well as mDCs
      deficient for these receptors. RESULTS: Compared with the controls (native OVA
      and OVA thermally processed without glucose), AGE-OVA enhanced the activation of
      OVA-specific CD4(+) T cells on coculture with mDCs, indicating that the glycation
      of OVA enhanced the T-cell immunogenicity of the allergen. The mDC uptake of AGE
      OVA was significantly higher than that of the controls. We identified scavenger
      receptor class A type I and II (SR-AI/II) as a mediator of the AGE-OVA uptake,
      whereas the receptor for AGEs and galectin-3 were not responsible. Importantly,
      the activation of OVA-specific CD4(+) T cells by AGE-OVA was attenuated on
      coculture with SR-AI/II-deficient mDCs. CONCLUSION: SR-AI/II targets AGE-OVA to
      the MHC class II loading pathway in mDCs, leading to an enhanced CD4(+) T-cell
      activation. The Maillard reaction might thus play an important role in the T-cell
      immunogenicity of food allergens.

PMID- 19864012
TI  - Effects of airport screening X-irradiation on bovine sperm chromatin integrity
      and embryo development.
AB  - Biological samples, including cryopreserved sperm, are routinely X-rayed during
      air shipment. The goal was to investigate the impact of X-irradiation used for
      checked and carry-on luggage on bovine sperm chromatin integrity and
      postfertilization in vitro embryonic development. Frozen domestic bull sperm (Bos
      taurus) (n=9 bulls) stored in a dry shipper (-160 degrees C) was screened by X
      irradiation 0, 1, 2, and 3 times as either carry-on or checked luggage. Duplicate
      straws were thawed, and sperm were assessed for chromatin damage using the sperm
      chromatin structure assay (SCSA) and by postfertilization in vitro developmental
      competence of mature oocytes. Multiple exposure to X-rays did not significantly
      affect sperm chromatin integrity assessed by SCSA. There were lower proportions
      of oocytes cleaved (P=0.07; 21.6+/-3.1% vs. 29.4+/-3.1%, 24.9+/-3.1%, and 25.7+/
      3.3% for 3 vs. 0, 1, and 2 times, respectively; least-squares means+/-SEM) and
      that developed to blastocysts (P=0.06; 9.0+/-1.7% vs. 13.8+/-1.7%, 11.5+/-1.7%,
      and 12.6+/-1.9%, respectively) when fertilization was performed with sperm X
      rayed 3 times using checked luggage irradiation; developmental competence
      (percentage cleaved embryos becoming blastocysts) was unaffected. There were no
      deleterious effects of other X-irradiation treatments on embryo development. We
      inferred that screening by X-irradiation may reduce the ability of sperm to
      activate oocyte cleavage after multiple exposures at the checked luggage dose.
      However, there was no evidence that competence of embryos to become blastocysts
      was reduced by X-irradiation (45.4+/-5.7%, 40.4+/-5.7%, 46.4+/-6.1%, and 41.8+/
      5.7% for 0, 1, 2, and 3 doses, respectively), but potential long-term epigenetic
      effects are unknown.

PMID- 19864013
TI  - Influence of hormonal and nonhormonal estrus synchronization methods on
      follicular and oocyte quality in primiparous lactating does at early postpartum
      period.
AB  - High-yield lactating does need effective estrus synchronization methods to
      improve their reproductive outcome by enhancing ovarian function. The aim of the
      current work was to analyze ovarian follicular and oocyte characteristics of
      hormonal and nonhormonal estrus synchronization regimes in primiparous lactating
      rabbit does (Oryctolagus cuniculus) in the early postpartum period (Day 11).
      Females were randomly treated with either (1) a hormonal standard treatment with
      25 IU equine chorionic gonadotropin (eCG) 48h before artificial insemination (eCG
      group) or (2) an alternative nonhormonal treatment consisting of doe-litter
      separation 24h before artificial insemination (Bio group). No significant
      differences were found in serum estradiol and progesterone concentrations between
      experimental groups. During the histologic study, the Bio group presented a
      higher number of primordial (P<0.05) and primary follicles (P=0.07) compared with
      that of the eCG group, whereas secondary and antral follicular populations were
      similar. Rates of late atretic follicles assessed by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique were not
      different between treatments, but the eCG group showed a significantly higher
      number of mid-atretic follicles compared with that of the Bio group. Nuclear in
      vitro oocyte maturation (IVM), measured as metaphase II rate, and in vitro
      steroidogenic response of cumulus-oocyte complexes, measured by ELISA, did not
      show significant differences between treatments. However, confocal study showed
      that cytoplasmic maturation of oocytes, in terms of cortical granule migration
      rate, was significantly higher in the Bio group compared with that after the eCG
      treatment. In conclusion, transient doe-litter separation seems to improve
      ovarian response in terms of follicular health and oocyte competence compared
      with that after the eCG treatment. Therefore, a 24-h-long transient weaning could
      be an alternative nonhormonal method for synchronizing estrus in primiparous
      lactating rabbit does inseminated in the early postpartum period.

PMID- 19864014
TI  - Production of good-quality porcine blastocysts by in vitro fertilization of
      follicular oocytes vitrified at the germinal vesicle stage.
AB  - We investigated survival, meiotic competence, cytoplasmic maturation, in vitro
      fertilization, and development of immature porcine (Sus scrofa) oocytes
      cryopreserved by a modified solid surface vitrification protocol. Cumulus-oocyte
      complexes (COCs) collected from follicles 3 to 6mm in diameter in abattoir
      derived ovaries of prepubertal gilts were either vitrified (Vitrified group),
      subjected to cryoprotectant treatment (CPA group), or used without any treatment
      (Control group). Oocyte viability was assayed by staining with fluorescein
      diacetate. Live oocytes were matured in vitro and their meiotic progression
      investigated by nuclear staining. In a series of experiments, the glutathione
      (GSH) content of in vitro-matured oocytes and viability of cumulus cells were
      assayed simultaneously. The in vitro-matured oocytes were also fertilized and
      cultured in vitro to assess their ability to be fertilized and to develop to the
      blastocyst stage, respectively. The proportion of viable oocytes in the Vitrified
      group was significantly lower than that in the CPA and Control groups (27.7%,
      90.4%, and 100%, respectively). Among the three groups, there were no differences
      in meiotic competence, cumulus viability, and GSH levels at the end of in vitro
      maturation. Fertilization parameters (i.e., rates of male pronucleus formation,
      monospermy, and second polar body extrusion) were also similar among groups.
      However, comparison of the developmental abilities of oocytes in the Vitrified,
      CPA, and Control groups revealed that the Vitrified group had a significantly
      reduced ability to undergo first cleavage (34.4%, 63.3%, and 69.0%) and to
      develop to the blastocyst stage (5.1%, 25.5%, and 34.6%). The mean total cell
      numbers in blastocysts after 6 d of culture were not significantly different
      among the Vitrified, CPA, and Control groups (40.3, 42.8, and 43.4). In
      conclusion, despite low survival rates and impaired development in the Vitrified
      group, meiotic competence, cytoplasmic maturation, and subsequent fertilization
      characteristics of surviving germinal vesicle oocytes were unaffected by
      vitrification, and high-quality blastocysts were produced from vitrified immature
      oocytes.

PMID- 19864015
TI  - Language or music, mother or Mozart? Structural and environmental influences on
      infants' language networks.
AB  - Understanding how language emerged in our species calls for a detailed
      investigation of the initial specialization of the human brain for speech
      processing. Our earlier research demonstrated that an adult-like left-lateralized
      network of perisylvian areas is already active when infants listen to sentences
      in their native language, but did not address the issue of the specialization of
      this network for speech processing. Here we used fMRI to study the organization
      of brain activity in two-month-old infants when listening to speech or to music.
      We also explored how infants react to their mother's voice relative to an unknown
      voice. The results indicate that the well-known structural asymmetry already
      present in the infants' posterior temporal areas has a functional counterpart:
      there is a left-hemisphere advantage for speech relative to music at the level of
      the planum temporale. The posterior temporal regions are thus differently
      sensitive to the auditory environment very early on, channelling speech inputs
      preferentially to the left side. Furthermore, when listening to the mother's
      voice, activation was modulated in several areas, including areas involved in
      emotional processing (amygdala, orbito-frontal cortex), but also, crucially, a
      large extent of the left posterior temporal lobe, suggesting that the mother's
      voice plays a special role in the early shaping of posterior language areas. Both
      results underscore the joint contributions of genetic constraints and
      environmental inputs in the fast emergence of an efficient cortical network for
      language processing in humans.

PMID- 19864016
TI  - Gonadal alterations in male eelpout (Zoarces viviparus) exposed to
      ethinylestradiol and trenbolone separately or in combination.
AB  - To evaluate the interaction between 17beta-trenbolone (TB) and 17alpha
      ethinylestradiol (EE2) in relevant environmental concentrations, male eelpout
      Zoarces viviparus were exposed in a flow-through seawater-system for 21 days to 5
      ng l-1 EE2, 5 ng l-1 or 20 ng l-1 TB or to combinations of both compounds. The
      effects on hepatosomatic index (HSI), gonadosomatic index (GSI) and gonadal
      histology were studied. No significant effects on HSI were observed in any
      treatment; in contrast, decreased GSI was observed in males exposed to EE2 alone
      or in combination with TB compared to controls (p<0.05). The histology revealed
      that the males were in the beginning of spermatogenesis. Males from the control
      group and some from the TB groups showed tubules with cysts containing
      spermatogonia, spermatocytes and spermatids; however, some testes of males
      exposed to TB showed slight to moderate interstitial fibrosis. Nevertheless, the
      most severely affected were males exposed to EE2 showing marked interstitial
      fibrosis, necrosis of germinal cells and reduced number of spermatocytes and
      spermatogonia in the cyst. Likewise, increased tubule number and proportionally
      decreased tubule diameter were observed in the testis of all EE2 exposed groups
      (p<0.05). Finally, a similar tubule number was observed in males exposed to
      EE2+20 ng l-1 TB compared to control (p>0.05). This study shows that EE2
      dramatically disrupts the spermatogenesis and low doses of 17beta-trenbolone are
      unable to effectively counteract the morphological effects of EE2.

PMID- 19864017
TI  - The adherence of platelets to adsorbed albumin by receptor-mediated recognition
      of binding sites exposed by adsorption-induced unfolding.
AB  - Although albumin (Alb) is the most abundant plasma protein, it is considered to
      be non-adhesive to platelets, as it lacks any known amino acid sequences for
      binding platelet receptors. Recent studies have suggested that platelets adhere
      to adsorbed Alb by mechanisms linked to its conformational state. To definitively
      address this issue we used circular dichroism (CD) spectropolarimetry to
      characterize the conformation of Alb adsorbed on a broad range of surface
      chemistries from a wide range of Alb solution concentrations, with platelet
      adhesion examined using a lactate dehydrogenase (LDH) assay and scanning electron
      microscopy (SEM). Our results prove that platelets bind to adsorbed Alb through
      receptor-mediated processes, with binding sites in Alb exposed and/or formed by
      adsorption-induced protein unfolding. Most importantly, beyond a critical degree
      of unfolding, the platelet adhesion levels correlated strongly with the
      adsorption-induced unfolding in Alb. The blockage of Arg-Gly-Asp (RGD) specific
      platelet receptors using an Arg-Gly-Asp-Ser (RGDS) peptide led to significant
      inhibition of platelet adhesion to adsorbed Alb, with the extent of inhibition
      and morphology of adherent platelets being similar for both Alb and Fg. Chemical
      neutralization of arginine (Arg) residues in the adsorbed Alb layer inhibited
      platelet-Alb interactions significantly, indicating that Arg residues play a
      prominent role in mediating platelet adhesion to Alb. These results provide
      deeper insight into the molecular mechanisms that mediate the interactions of
      platelets with adsorbed proteins, and how to control these interactions to
      improve the blood compatibility of biomaterials for cardiovascular applications.

PMID- 19864018
TI  - Biological responses to hydroxyapatite surfaces deposited via a co-incident
      microblasting technique.
AB  - Hydroxyapatite (HA) is routinely used as a coating on a range of press-fit
      (cementless) orthopaedic implants to enhance their osseointegration. The standard
      plasma spraying method used to deposit a HA surface layer on such implants often
      contains unwanted crystal phases that can lead to coating delamination in vivo.
      Consequently, there has been a continuous drive to develop alternate surface
      modification technologies that can eliminate the problems caused by a non-optimal
      coating process. In this study two methods for creating a HA layer on metal
      alloys that employ micro-blasting have been evaluated to determine if the
      inclusion of an abrasive agent can enhance the in vitro and in vivo performance
      of the modified surface. The first method employs direct micro-blasting using HA
      as the abrasive media, while the second employs a simultaneous blasting with an
      alumina abrasive and coincident blasting with HA as a dopant. Whereas, both
      methods were found to produce a surface which was enriched with HA, the
      respective microstructures created were significantly different. Detailed surface
      characterisation revealed that the use of the abrasive produced disruption of the
      metal surface without producing detectable incorporation of alumina particles.
      Roughening of the metal surface in this way breached the passivating oxide layer
      and created sites which subsequently provided for impregnation, mechanical
      interlocking and chemical bonding of HA. The co-incident use of an alumina
      abrasive and a HA dopant resulted in a stable surface that demonstrated enhanced
      in vitro osteoblast attachment and viability as compared to the response to the
      surface produced using HA alone or the metal substrate control. Implantation of
      the surface produced by co-incident blasting with alumina and HA in a rabbit
      model confirmed that this surface promoted the in vivo formation of early stage
      lamellar bone growth.

PMID- 19864019
TI  - Surfaces modified with nanometer-thick silver-impregnated polymeric films that
      kill bacteria but support growth of mammalian cells.
AB  - Silver is widely used as a biocidal agent in ointments and wound dressings.
      However, it has also been associated with tissue toxicity and impaired healing.
      In vitro characterization has also revealed that typical loadings of silver
      employed in ointments and dressings (approximately 100 microg/cm(2)) lead to
      cytotoxicity. In this paper, we report the results of an initial study that
      sought to determine if localization of carefully controlled loadings of silver
      nanoparticles within molecularly thin films immobilized on surfaces can lead to
      antimicrobial activity without inducing cytotoxicity. Polymeric thin films of
      poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) were prepared
      by layer-by-layer deposition and loaded with approximately 0.4 microg/cm(2) to
      approximately 23.6 microg/cm(2) of silver nanoparticles. Bacterial killing
      efficiencies of the silver-loaded films were investigated against Staphylococcus
      epidermidis, a gram-positive bacterium, and it was determined that as little as
      approximately 0.4 microg/cm(2) of silver in the polymeric films caused a
      reduction of 6log(10)CFU/mL (99.9999%) bacteria in suspensions incubated in
      contact with the films (water-borne assays). Significantly, whereas the
      antibacterial films containing high loadings of silver were found to be toxic to
      a murine fibroblast cell line (NIH-3T3), the polymeric films containing
      approximately 0.4 microg/cm(2) of silver were not toxic and allowed attachment,
      and growth of the mammalian cells. Thus, the results of this study go beyond
      prior reports by identifying silver-impregnated, polymeric thin films that are
      compatible with in vitro mammalian cell culture yet exhibit antibacterial
      activity. These results support the hypothesis that localization of carefully
      controlled loadings of silver nanoparticles within molecularly thin polymeric
      films can lead to antimicrobial activity without cytotoxicity. More broadly, this
      strategy of modifying surfaces with minimal loadings of bioactive molecules
      indicates the basis of approaches that may permit management of microbial burden
      in wound beds without impairment of wound healing.

PMID- 19864020
TI  - Glyceroltrinitrate facilitates stimulated CGRP release but not gene expression of
      CGRP or its receptor components in rat trigeminal ganglia.
AB  - Nitric oxide (NO) donors induce delayed headaches in migraineurs. In a
      corresponding rat model NO donors cause delayed ongoing activity in central
      trigeminal neurons which process intracranial afferent input. Cellular models
      indicate that NO may increase the release or production of calcitonin gene
      related peptide (CGRP), a key mediator in primary headaches. CGRP release from
      intact isolated trigeminal ganglia of adult male Wistar rats was investigated in
      vitro. Exposure to high NO donor concentrations did not affect basal or
      stimulated CGRP release. After a two hour infusion of the NO donor
      glyceroltrinitrate (250microg/kg/h), however, inflammatory mediators-induced CGRP
      release was 80% higher compared to control animals. Administration of the soluble
      guanylate cyclase inhibitor ODQ or the application of 8Br-cGMP revealed a cGMP
      independent mechanism. In four groups of separate experiments total mRNA was
      extracted from rat trigeminal ganglia up to 6h after glyceroltrinitrate or saline
      infusion. Gene expression of CGRP and the CGRP-receptor components, receptor
      activity-modifying protein 1, receptor component protein and calcitonin receptor
      like receptor was measured by quantitative RT-PCR. Glyceroltrinitrate infusion
      did not change mRNA levels of these genes compared to infusion of saline. The
      present data suggest that prolonged increase in NO levels facilitates stimulated
      CGRP release from trigeminal ganglion neurons. The underlying mechanism appears
      to be independent of the cGMP pathway and not to interact with CGRP in the
      trigeminal ganglion. Delayed headaches induced by NO may change CGRP or CGRP
      receptor expression.

PMID- 19864021
TI  - The need for a General Comment for Article 19 of the UN Convention on the Rights
      of the Child: Toward enlightenment and progress for child protection.
AB  - OBJECTIVE: To present the need and plan for development of a General Comment for
      the UN Convention on the Rights of the Child Article 19 which has the potential
      to transform and advance child protection through the infusion of a child rights
      approach. METHODS: The Committee on the Rights of the Child (Committee)
      authorized ISPCAN and IICRD to draft a General Comment for CRC Article 19 (GC19)
      and to introduce implementation supports. An international working group
      (GC19WG), Expert Advisory Panel (EAP), and GC19 Focal Group of Committee members
      (GC19 CRC FG) have been organized to help guide and carry out the program of
      development. Analyses of relevant histories and knowledge, including effective
      and promising child protection strategies, are being applied to guide formulation
      of the GC and high priority implementation components. Consultations on the draft
      and supportive products will be conducted in cooperation with UNICEF, WHO, the
      NGO Group for the CRC, and other NGOs. Advice is to be solicited from interested
      parties and organizations in person and through distance communication throughout
      the world. RESULTS: In addition to the GC19, numerous implementation supports
      will be planned and some will be produced and piloted during the program of
      development. Under consideration are an implementation guide and resources;
      commentary; accountability models, indicators, measures and evaluation systems; a
      clearing house and resource website; a child-appropriate version of GC19; and
      education/training curricula and programs. PRACTICE IMPLICATIONS: GC19 has the
      potential to transform child protection by fostering a paradigm shift in its
      conceptualization, theory, research, and practice. Article 19 encourages an
      interpretation and application beyond narrow child protection conceptualizations
      and practices which have been found seriously inadequate. The General Comment can
      advance effective prevention of maltreatment and protection of personal security
      by promoting the child's rights, well-being, health, and development in all
      aspects of child protection. GC19 will provide support to the Committee on the
      Rights of the Child in its monitoring and guiding functions, and to States
      Parties, professionals, and civil society agents concerned with the protection
      and well-being of children.

PMID- 19864022
TI  - Twenty years of the Convention on the Rights of the Child: Achievements and
      challenges for child protection.

PMID- 19864023
TI  - Issues in program planning and evaluation with immigrant children and families
      involved in the child welfare system.

PMID- 19864024
TI  - Anthropogenic and naturally-produced organobrominated compounds in marine mammals
      from Brazil.
AB  - Liver samples from 51 cetaceans, comprising 10 species, stranded between 1994 and
      2006 in a highly industrialized and urbanized region in Southeast Brazil, were
      analyzed for polybrominated diphenyl ethers (PBDEs) and methoxylated-PBDEs (MeO
      PBDEs). A concentration range of PBDEs (3-5960ng/g lw) similar to that observed
      in Northern Hemisphere dolphins was found. MeO-PBDE concentrations in continental
      shelf (CS) dolphins from Brazil are among the highest detected to date in
      cetaceans (up to 250microg/g lw). Higher SigmaMeO-PBDE concentrations were
      measured in CS and oceanic dolphins than in estuarine dolphins. The
      SigmaPBDE/SigmaMeO-PBDE ratio varied significantly ranging from a mean value of
      7.12 to 0.08 and 0.01 for estuarine, CS and oceanic species, respectively. A
      positive correlation was observed between SigmaPBDE and year of stranding of male
      estuarine dolphins (Sotalia guianensis), which suggests temporal variation in the
      exposure. Placental transfer of organobrominated compounds was also evidenced in
      S. guianensis.

PMID- 19864025
TI  - Immunomodulation by phosphocholine--biosynthesis, structures and immunological
      implications of parasitic PC-epitopes.
AB  - Phosphocholine (PC) as a small haptenic molecule present on antigens of parasites
      can provoke various effects on immune cells leading to immunomodulation of the
      host's immune system. This immunomodulation not only allows long-term persistence
      but also prevents severe pathology due to down-regulation of cellular immune
      responses. Additionally, PC plays an important role for development and fertility
      of the parasites. To fully understand the mechanisms of immunomodulation the
      detailed knowledge of the biosynthesis of the PC-epitopes, their molecular
      structure and biological function has to be elucidated. The implication of
      parasite-specific transferases in the biosynthesis of the PC-epitopes and the
      sensitivity of parasites towards disruption of the choline metabolism offers new
      perspectives for the development of anti-parasitic drugs and therapies.
      Furthermore, the immunomodulation provoked by PC-epitopes preventing inflammatory
      reactions may be useful in the treatment of inflammatory diseases. This review
      summarizes the current knowledge on the biosynthesis of PC-epitopes, their
      structures and immunological implications.

PMID- 19864026
TI  - Involvement of the c-jun N-terminal kinases JNK1 and JNK2 in complement-mediated
      cell death.
AB  - Cell death and survival signals activated by the complement membrane attack
      complex C5b-9 play important roles in complement-associated diseases and in
      antibody-based cancer therapy. Here, we investigated the involvement of the JNK
      mitogen-activated protein kinase in C5b-9-induced cell lysis. Necrotic-type cell
      death regulation by JNK1 and JNK2 was selectively studied in mouse fibroblasts
      and human K562, HeLa and 293T cells. C5b-9 induced higher JNK activation than C5b
      8. Pretreatment with a JNK inhibitor reduced cell sensitivity to complement
      mediated lysis. KO cells deficient in either JNK1 or JNK2 were less sensitive to
      lysis than WT cells. This correlated with lower C3 and C5b-9 deposition on KO
      cells. Furthermore, silencing of JNK1 or JNK2 expression by RNA interference
      decreased cell lysis by complement. Reconstitution of JNK2 into JNK2-/- cells and
      over expression of JNK2 in WT cells increased C3 and C5b-9 deposition as well as
      cell sensitivity to complement-mediated lysis. Pretreatment of cells with the
      phosphotyrosine phosphatase inhibitor phenylarsine oxide increased JNK activation
      and JNK-dependent complement-mediated necrotic death of WT and JNK2-/- KO cells
      but not of JNK1-/- KO cells. The JNK inhibitor and PAO had no effect on
      complement-mediated lysis in cells lacking Bid, suggesting involvement of Bid in
      the JNK lytic pathway. Our results demonstrate that complement C5b-9 induce a
      JNK/Bid-dependent and JNK-independent necrotic cell death. Both JNK1 and JNK2
      have cytotoxic potential, however JNK2 is the primary signal transducer.

PMID- 19864027
TI  - Humanization of an agonistic anti-death receptor 4 single chain variable fragment
      antibody and avidity-mediated enhancement of its cell death-inducing activity.
AB  - Development of agonistic monoclonal antibodies (mAbs) against the pro-apoptotic
      molecule death receptor 4 (DR4) [or tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL) receptor 1] is an attractive anti-cancer strategy because
      of their potential for inducing tumor-specific cell death. In this study, we
      humanized an agonistic anti-DR4 AY4 scFv raised in mice (mAY4) by grafting the
      complementarity-determining regions (CDRs) onto a fixed human framework, while
      preserving the so-called Vernier zone residues, a group of framework (FR)
      residues directly underneath the CDRs, with the murine residues in the humanized
      antibody, hAY4. The humanized hAY4 scFv maintained the antigen binding affinity
      and epitope specificity of mAY4. To investigate how the valence of hAY4 scFv
      affects DR4-mediated cell death, bivalent and trivalent forms of hAY4 scFv were
      generated by linking a hinge region to the coiled-coil domain of a dimerizing
      leucine zipper and trimerizing isoleucine zipper, respectively. Compared to the
      monovalent and bivalent forms, the trivalent hAY4 scFv induced more potent
      caspase-dependent apoptotic cell death as evidenced by increased activation of
      caspase-8 and downstream pro-apoptotic molecules. Our results suggest that like
      other TNF family receptors, avidity-mediated oligomerization of DR4 augments the
      receptor-mediated apoptotic cell death by promoting intracellular cell death
      signaling.

PMID- 19864028
TI  - Model mechanisms of sulfhydryl oxidation by methyl- and benzeneseleninic acid,
      inhibitors of zinc-finger transcription factors.
AB  - The toxicity of selenium is a major barrier to its application to the prevention
      of cancer, cardiovascular disease, and other chronic ailments. Organic seleninic
      acids, as well as other reducible selenium compounds, have been shown to react
      with biological sulfhydryls to disrupt a variety of biochemical signaling
      pathways, including transcription and recognition by zinc-finger proteins. Using
      density-functional theory (DFT) and solvent-assisted proton exchange, the thiol
      reduction mechanisms of methyl- and benzeneseleninic acid have been modeled as
      distinct two-step pathways with intermediates as either a seleninyl sulfide or a
      hypervalent selenurane. The activation barrier for the first step to the
      selenurane intermediate is 10-13kcal/mol lower than the seleninyl sulfide. For
      the second step, reduction of the selenurane is slightly more energetically
      favorable than for the seleninyl sulfide, primarily due to the implicit solvation
      correction. The barrier for step two using either intermediate is greater than
      that of the first step which is consistent with experimental studies that assign
      the reduction of the intermediate as the rate-determining step. The summary of
      the DFT results suggest that the reaction pathway is (1) addition of thiol to the
      seleninic acid to form a short-lived selenurane; (2) rearrangement of the
      selenurane to the seleninyl sulfide; and (3) reduction of the seleninyl sulfide
      by the second equivalent of thiol.

PMID- 19864029
TI  - A comparative study of non-fatal self-poisoning with antidepressants relative to
      prescribing in three centres in England.
AB  - BACKGROUND: Antidepressants are used frequently in non-fatal self-poisoning.
      There are national guidelines for prescribing antidepressants. There have been
      few investigations of how non-fatal self-poisoning with antidepressants varies in
      relation to prescribing and to patient characteristics. METHODS: A comparative
      study of the use of specific antidepressants (amitriptyline and dosulepin
      (tricyclics), citalopram, fluoxetine, paroxetine and sertraline (selective
      serotonin reuptake inhibitors) and venlafaxine (serotonin norepinephrine reuptake
      inhibitor)) for non-fatal self-poisoning (episode-based), relative to
      prescribing, in three centres in England, 2004 to 2006. RESULTS: There was marked
      variation between centres in the ratio of rates of self-poisoning to prescribing
      for specific antidepressants. Higher rates of self-poisoning relative to
      prescribing for all antidepressants combined, and for venlafaxine, were found in
      the centre with greater proportions of patients with a history of self-harm
      and/or previous psychiatric treatment. Within each centre, higher rates of self
      poisoning relative to prescribing were found for citalopram and fluoxetine than
      amitriptyline. However, rates of self-poisoning relative to prescribing for
      either amitriptyline or dosulepin were also similar to sertraline, which is of
      concern given the known toxicity of tricyclics. LIMITATIONS: An ecological study,
      where prescriptions were for all indications and not specifically for the
      patients who self-poisoned. CONCLUSIONS: Marked differences found in ratios of
      self-poisoning with antidepressants to levels of prescribing, in three centres in
      England, are likely to reflect differences in both prescribing practices (despite
      clear national guidance) and patient characteristics. Risk of overdose and
      toxicity should be considered when local prescribing policy and clinical practice
      relating to antidepressants are under review.

PMID- 19864030
TI  - Sphenoid sinus development in choanal atresia.
AB  - OBJECTIVES: To study the growth and size of the sphenoid sinuses in choanal
      atresia patients. STUDY DESIGN: Case-control single blinded retrospective study.
      METHODS: Fifteen non-syndromic patients (ages 0-26 years old) were selected
      because they had at least one suitable CT scan (nine bilateral and 11
      unilateral=total 20 scans). Twenty age-matched CT scans were used as controls.
      The following linear measurements were obtained: (1) fronto-zygomatic width, (2)
      zygomatic width, (3) width of the maxillary sinuses, (4) width of the sphenoid
      sinuses. Statistical analysis was performed with the exact permutation test in
      the framework of a parametric analysis of a randomized completed block. RESULTS:
      The width measurements of the choanal atresia CT scans did not show any
      statistically significant difference when compared to their control CT scans
      except for the zygomatic width in the bilateral choanal atresia patients. In the
      latter, the width was smaller (p=0.03). CONCLUSIONS: In unilateral and bilateral
      choanal atresia patients, there is normal growth of the width of the sphenoid
      sinuses.

PMID- 19864031
TI  - Connexin 43 expression is associated with vascular activation in human radial
      artery.
AB  - The gap junction protein, connexin 43 (Cx43) might be involved in the development
      of atherosclerosis. However, little is known about Cx43 expression in human
      arteries. We histologically analyzed the distal portions of radial (RA) and
      internal thoracic arteries (ITAs) obtained from 29 patients undergoing coronary
      artery bypass graft surgery. The medial smooth muscle cells of RA expressed Cx43,
      the intensity of which correlated with nuclear factor kappa B (NFkappaB)
      activation. In contrast, the expression of Cx43 in ITA did not correlate with
      NFkappaB activation. Cx43 appears to be involved in the pathogenesis of
      atherosclerosis especially in muscular arteries.

PMID- 19864032
TI  - Arginine and lysine decarboxylases and the acid tolerance response of Salmonella
      Typhimurium.
AB  - Salmonella Typhimurium CECT 443 inactivation at pH 2.5 in Mineral Medium (MM) and
      MM supplemented with 0.01% (w/v) arginine, lysine or glutamic acid was studied
      using stationary-phase cells grown in buffered BHI pH 7.0 (non-acid adapted
      cells) and acidified BHI up to pH 4.5 with acetic, citric, lactic and
      hydrochloric acids (acid adapted cells). In all cases, acid adapted cells, with D
      values ranging from 23.34 to 86.90 min, showed a significantly higher acid
      resistance than non-acid adapted cells, with D-values between 8.90 and 10.29 min.
      Whereas the conditions used for acid adaptation did not exert a significant
      effect on the acid resistance of the S. Typhimurium CECT 443 resulting cells, the
      inclusion of lysine and arginine in the challenge medium protected them against
      acid inactivation, reaching D-values of about 2 and 3 times higher, respectively,
      than those found in MM or MM supplemented with glutamic acid. None of these three
      amino acids significantly modified the acid resistance of non-acid adapted cells.
      The relative expression level of adiA (encoding the arginine decarboxylase), adiY
      (encoding the transcriptional activator of adiA), cadA (encoding the lysine
      decarboxylase) and cadB (encoding the lysine/cadaverine transport protein) was
      examined by quantitative PCR. Acid adapted cells showed higher relative
      expression levels for both systems, arginine decarboxylase and lysine
      decarboxylase, which demonstrates that the induction of specialized pH
      homeostatic systems plays an important role in S. Typhimurium CECT 443 protection
      against acid stress. However, the increased acid resistance showed by acid
      adapted cells challenged in MM arginine or lysine free suggests the existence of
      other microbial survival strategies.

PMID- 19864033
TI  - Effect of high pressure CO2 and mild heat processing on natural microorganisms in
      apple juice.
AB  - Apple juice was pasteurized by high pressure carbon dioxide (HPCD) at 20MPa with
      CO(2) concentration of 4.5-5.3% and mild heat (MH) at atmospheric pressure.
      Microbial inactivation and stability of natural microorganisms in apple juice
      were investigated. The temperatures were 37, 42, 47, 52, 57 and 62 degrees C,
      treatment time was 30min, and storage temperatures of pasteurized apple juice
      were 2 and 28 degrees C. The aerobic bacteria (AB) treated by MH at 62 degrees C
      and by HPCD at > or =52 degrees C were almost totally inactivated, the microbial
      counts were<10CFU/mL. The yeasts and moulds (Y&M) treated by MH at > or =57
      degrees C and by HPCD at > or =42 degrees C were totally inactivated. HPCD
      increased the susceptibility of these natural microorganisms to temperature and
      enhanced their microbial inactivation. The AB in apple juice treated by HPCD at >
      or =52 degrees C and the Y&M treated by HPCD at > or =57 degrees C, the AB and
      the Y&M treated by MH at 62 degrees C showed a better stability during storage at
      2 and 28 degrees C, but apple juice treated by HPCD at < or =47 degrees C was
      characterized with high microbial counts of the AB> or =2.75x10(3)CFU/ml. A
      viable but non-culturable (VBNC) state of the Y&M treated by MH at 57 degrees C
      and by HPCD at 42, 47 and 52 degrees C was observed during storage at 28 degrees
      C. Apparently the proper temperature of HPCD treatment of apple juice at 20MPa
      and stored at 2 and 28 degrees C was greater than or equal to 52 degrees C, while
      for MH treatment the proper temperature increased to 62 degrees C in this study.

PMID- 19864034
TI  - Early prediction of short-term development of hepatic encephalopathy in patients
      with acute liver disease unrelated to paracetamol. A prospective study in Japan.
AB  - BACKGROUND/AIMS: The aim of our study was to provide a predictive model for early
      recognition of the risk of short-term development of hepatic encephalopathy (HE)
      in patients with symptomatic acute liver disease (ALD). METHODS: From a
      retrospective analysis of 220 patients with ALD, prothrombin time (PT) equal to,
      or lower than, 80% of normal, was set as the registration criteria in the
      subsequent patient cohorts of the study. Then, a HE-prediction model was derived
      by a logistic regression analysis of data in 259 new patients, and prospectively
      validated in 124 other patients, both groups of patients were affected by ALD
      unrelated to paracetamol (non-P ALD). RESULTS: The following HE-prediction model
      was established: lambda = [0.692 x ln(1 + total bilirubin(mg/dL))] - 0.065 x
      PT(%) + [1.388 x Age(years)] + [0.868 x Etiology] - 1.156, where Age is 1 in
      patients older than 50 years and Etiology is 1 when the cause of non-P ALD is
      flare-up of type B hepatitis, auto-immune hepatitis or unknown, and 0 otherwise.
      In the validation group, according to the model-based risk of subsequent
      development of HE, sensitivity and specificity of the model were 100% and 69.0%,
      respectively, in patients with an evaluated risk lower than 20%, and 62.5% and
      93.1%, respectively, in those with an evaluated risk equal to, or greater than,
      50%. CONCLUSION: In Japanese patients with symptomatic non-P ALD, our model,
      which includes four of the five items used in the King's College Hospital
      criteria, represents an acceptable, effective model to allow early detection of
      the risk of short-term development of HE. Using this model in other populations
      requires further validation specific to each of them.

PMID- 19864037
TI  - Ursodeoxycholic acid and primary biliary cirrhosis: EASL and AASLD guidelines.

PMID- 19864035
TI  - Transarterial chemotherapy alone versus transarterial chemoembolization for
      hepatocellular carcinoma: a randomized phase III trial.
AB  - BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) is a combination
      of transarterial infusion chemotherapy (TAI) and embolization, and has been
      widely used to treat patients with hepatocellular carcinoma (HCC). However, since
      the impact of adding embolization on the survival of patients treated with TAI
      had never been evaluated in a phase III study, we conducted a multi-center, open
      label trial comparing TACE and TAI to assess the effect of adding embolization on
      survival. METHODS: Patients with newly diagnosed unresectable HCC were randomly
      assigned to either a TACE group or a TAI group. Zinostatin stimalamer was
      injected into the hepatic artery, together with gelatin sponge in the TACE group
      and without gelatin sponge in the TAI group. Treatment was repeated when follow
      up computed tomography showed the appearance of new lesions in the liver or re
      growth of previously treated tumors. RESULTS: Seventy-nine patients were assigned
      to the TACE group, and 82 were assigned to the TAI group. The two groups were
      comparable with respect to their baseline characteristics. At the time of the
      analysis, 51 patients in the TACE group and 58 in the TAI group had died. The
      median overall survival time was 646 days in the TACE group and 679days in the
      TAI group (p=0.383). CONCLUSIONS: The results of this study suggest that
      treatment intensification by adding embolization did not increase survival over
      TAI with zinostatin stimalamer alone in patients with HCC.

PMID- 19864038
TI  - Tubulin-related cortical dysgeneses: microtubule dysfunction underlying neuronal
      migration defects.
AB  - The fine tuning of proliferation and neurogenesis, neuronal migration and
      differentiation and connectivity underlies the proper development of the cerebral
      cortex. Mutations in genes involved in these processes are responsible for
      neurodevelopmental disorders, such as cortical dysgeneses, which are usually
      associated with severe mental retardation and epilepsy. Over the past few years,
      the importance of cytoskeleton components in cellular processes crucial for
      cortical development has emerged from a body of functional data. This was
      reinforced by the association of mutations in the LIS1 and DCX genes, which both
      encode proteins involved in microtubule (MT) homeostasis, with cerebral cortex
      developmental disorders. The recent discovery of patients with lissencephaly and
      bilateral asymmetrical polymicrogyria (PMG) carrying mutations in the alpha- and
      beta-tubulin-encoding genes TUBA1A and TUBB2B further supports this view, and
      also raises interesting questions about the specific roles played by certain
      tubulin isotypes during the development of the cortex.

PMID- 19864039
TI  - Intelligent model-based advisory system for the management of ventilated
      intensive care patients: Hybrid blood gas patient model.
AB  - Arterial blood gas (ABG) analyses are essential for assessing the acid-base
      status and guiding the adjustment of mechanical ventilation in critically ill
      patients. Conventional ABG sampling requires repeated arterial punctures or the
      insertion of an arterial catheter causing pain, haemorrhage and thrombosis to the
      patients. Less invasive and non-invasive blood gas analysers, with a technology
      still in transition, have offered some promise in the recent years. SOPAVent
      (Simulation of Patients under Artificial Ventilation) is a five compartment blood
      gas model which captures the basic features of respiratory physiology and gas
      exchange in the human lungs. It uses ventilator settings and routinely monitored
      physiological parameters as inputs to produce steady-state estimates of the
      patient's ABG. This paper overviews the original SOPAVent model and presents an
      improved data-driven hybrid model that is patient-specific and gives continuous
      and totally non-invasive ABG predictions. The model has been comprehensively
      tested in simulations and validated using recorded measurements of ABG and
      ventilator parameters from ICU patients.

PMID- 19864040
TI  - Plant cell proliferation and growth are altered by microgravity conditions in
      spaceflight.
AB  - Seeds of Arabidopsis thaliana were sent to space and germinated in orbit.
      Seedlings grew for 4d and were then fixed in-flight with paraformaldehyde. The
      experiment was replicated on the ground in a Random Positioning Machine, an
      effective simulator of microgravity. In addition, samples from a different space
      experiment, processed in a similar way but fixed in glutaraldehyde, including a
      control flight experiment in a 1g centrifuge, were also used. In all cases,
      comparisons were performed with ground controls at 1g. Seedlings grown in
      microgravity were significantly longer than the ground 1g controls. The cortical
      root meristematic cells were analyzed to investigate the alterations in cell
      proliferation and cell growth. Proliferation rate was quantified by counting the
      number of cells per millimeter in the specific cell files, and was found to be
      higher in microgravity-grown samples than in the control 1g. Cell growth was
      appraised through the rate of ribosome biogenesis, assessed by morphological and
      morphometrical parameters of the nucleolus and by the levels of the nucleolar
      protein nucleolin. All these parameters showed a depletion of the rate of
      ribosome production in microgravity-grown samples versus samples grown at 1g. The
      results show that growth in microgravity induces alterations in essential
      cellular functions. Cell growth and proliferation, which are strictly associated
      functions under normal ground conditions, appeared divergent after gravity
      modification; proliferation was enhanced, whereas growth was depleted. We suggest
      that the cause of these changes could be an alteration in the cell cycle
      regulation, at the levels of checkpoints regulating cell cycle progression,
      leading to a shortened G2 period.

PMID- 19864041
TI  - Use of a custom array to study differentially expressed genes during blood orange
      (Citrus sinensis L. Osbeck) ripening.
AB  - A flesh-specific oligonucleotide custom array was designed to study gene
      expression during blood orange ripening. The array included 301 probes derived
      from a subtracted SSH library, a cDNA-AFLP collection, and a set of regulatory
      genes from the Harvest citrus database. The custom array was hybridized using
      samples of Moro, a pigmented cultivar, and Cadenera, a common cultivar, at three
      different ripening stages: the immature phase, the halfway point of maturation
      (corresponding to the start of Moro pigmentation) and the full ripening. Of the
      301 probes, 27 in total, corresponding to 20 different transcripts, indicated
      differential expression in stage-to-stage and/or cultivar-to-cultivar
      comparisons. Transcripts encoding for anthocyanin biosynthesis represented most
      of the total over-expressed probes. The remaining differentially expressed
      transcripts were functionally associated with primary metabolism as flavor
      biosynthesis, defense and signal transduction. The expressed products associated
      with probes indicating differential expression were confirmed by qRT-PCR. The
      microarray was designed considering a small collection of sequences useful for
      monitoring specific pathways and regulatory genes related to fruit ripening and
      anthocyanin pigmentation. The main novelty of this customization is the use of
      expressed sequences specifically derived from blood orange flesh to study
      different cultivars and ripening stages, and the provision of further information
      about processes related to anthocyanin pigmentation in citrus fruit flesh.

PMID- 19864042
TI  - Dark-induced hormone changes coincide with the resumption of light-inhibited
      shoot growth in Catasetum fimbriatum (Orchidaceae).
AB  - Catasetum fimbriatum plants cultivated in the absence of light exhibit continuous
      shoot growth leading to the formation of nodes and internodes. On the other hand,
      when these plants are incubated in the presence of light, shoot longitudinal
      growth is inhibited and pseudobulbs develop just below the shoot apical meristem.
      These facts provide evidence of a possible influence of light on mitotic cell
      division in the shoot apex as well as on pseudobulb initiation. The effects of
      light and dark on the interruption and/or maintenance of shoot apex mitotic
      activity and the subsequent formation of pseudobulbs in the sub-meristematic
      regions were investigated by means of histological and hormonal studies. The
      interruption of shoot apex development occurred around the 150th d of light
      incubation and seems to have resulted from the establishment of a strong storage
      sink in the region of the future pseudobulb, in detriment to the continuous
      activity of the shoot apical meristem. The reduced total cytokinins/IAA ratio in
      the apex, mainly due to high levels of IAA, could be a key factor in the
      interruption of cell divisions. Transfer to the dark brings about the resumption
      of shoot apex development of plants through the re-entrance of cells in the cell
      cycle which coincides with a significant increase in the total cytokinins/IAA
      ratio.

PMID- 19864043
TI  - Spatiotemporal expression pattern of neuroepithelial stem cell marker nestin
      suggests a role in dermal homeostasis, neovasculogenesis, and tumor stroma
      development: a study on embryonic and adult human skin.
AB  - BACKGROUND: Whereas keratinocytic bulge stem cells are well characterized,
      comparably little is known about cutaneous mesenchymal stem cells. The follicular
      connective tissue sheath is proposed as a niche for dermal stem cells. OBJECTIVE:
      Because the neuroepithelial stem cell marker nestin represents a marker for
      mesenchymal stem cells in various tissues, our aim was to characterize its
      spatiotemporal expression pattern in the skin with special reference to the
      follicular mesenchyme. METHODS: We studied immunohistochemically nestin
      expression over the course of human cutaneous embryogenesis, in postnatal skin,
      in scalp wounds, and in the peritumoral stroma of basal cell carcinomas and
      compared its expression with that of other known mesenchymal markers. RESULTS:
      Nestin is expressed throughout the entire early embryonic dermis but confined
      later during development to the follicular connective tissue sheath, where it can
      also be found in postnatal human hair follicles. Its expression is up-regulated
      in scalp wounds and the nestin-positive cells seem to originate from the
      follicular mesenchyme. Nestin is also expressed in a thin layer of fibroblasts in
      the immediate vicinity of basal cell carcinomas. LIMITATIONS: The examination for
      nestin expression of scalp wounds is considered preliminary, because we examined
      scalp wounds representing re-excisions of previously diagnosed neoplasms from
      which we had no exact time table available as to when the original excision took
      place. CONCLUSION: We propose that nestin functions as a stem cell marker of the
      follicular mesenchyme and has a major regulatory role in dermal homeostasis,
      cutaneous neovasculogenesis, and tumor stroma development.

PMID- 19864044
TI  - [Right paracardiac mediastinal mass in the context of acute coronary syndrome].

PMID- 19864045
TI  - [Usefulness of cognitive plasticity evaluation in the differential diagnosis of
      cognitive impairment and depression-induced pseudo-dementia].
AB  - INTRODUCTION: A major challenge for gerontological research is to differentiate
      adequately between old adults with poor performance on cognitive tasks due to
      depression, and those who present cognitive impairment associated with dementia.
      In view of the fact that cognitive plasticity has already proved to be efficient
      in the diagnosis of age-associated cognitive impairment, mild cognitive
      impairment and dementia, the objective of this study is to investigate the
      possibility that it may also prove useful in the differential diagnosis of these
      two disorders. MATERIALS AND METHODS: A total of 50 old adults participated in
      the study. These completed the Positions Test (PT) and the Auditory Verbal
      Learning Test of Learning Potential (AVLT-LP) as measures of cognitive
      plasticity. Participants also undertook the Spanish version of Mini Mental State
      (MEC), Life Satisfaction Questionnaire (LSQ) and Geriatric Depression Scale
      (GDS). Socio-demographic data were also collected. RESULTS: With regard to
      cognitive plasticity, depressed old adults do not differ from those without
      depression. On the other hand, old adults with cognitive impairment present less
      cognitive plasticity than those without cognitive impairment. CONCLUSION:
      Cognitive plasticity appears to be a relevant variable in the differentiation
      between old people with low cognitive performance due to depression and old
      people with cognitive impairment.

PMID- 19864046
TI  - [Distinct forms of entering retirement and their relationship with psychological
      health].
AB  - INTRODUCTION: Due to a series of factors such as working conditions, economic
      position and health status, retirement does not necessarily occur at the age of
      65 years, thus generating new types of retirement. OBJECTIVES: To study the
      possible relationship between retirement types and psychological health
      indicators, i.e. depression, anxiety and life satisfaction and to analyze
      perceptions and feelings about the change produced as a result of retirement.
      MATERIALS AND METHODS: A total of 119 retired persons (68.1% men, 31.9% women)
      participated in this study. The mean age was 66.5 years. Participants were
      interviewed individually. The instruments used were the Short Portable Mental
      Status Questionnaire, an ad hoc interview, in which sociodemographic data and
      information on retirement were gathered, the Goldberg Anxiety and Depression
      Scale, the Philadelphia Geriatric Center Life Satisfaction Scale, and lastly, the
      COOP-WONCA Health-Related Quality of Life Scale. RESULTS: Participants who
      retired due to illness had higher levels of anxiety and depression and lower life
      satisfaction than persons retiring for other reasons. The ANOVA revealed
      statistically significant differences (p<.001) only in life satisfaction. After
      the corresponding regression analysis was performed on this variable, a
      statistically significant model was found that grouped together four predictive
      variables: anxiety (p<.001), depression (p<.001), income bracket (p<.001) and
      physical status (p<.05). These variables explained 46% of the variance.
      CONCLUSIONS: In line with other studies, the present study found that retirement
      is not associated with depression, although retirement due to illness is
      associated with poorer psychological health. The results on life satisfaction
      support the idea that retirement is no longer a homogeneous event. Retirement
      type does not appear to be a major predictor of life satisfaction.

PMID- 19864047
TI  - [Basal cell carcinoma simulating bilateral cervical adenopathies].

PMID- 19864048
TI  - [Current and lifetime depression as a risk factor for hospital admission in
      patients older than 74 years attended in an emergency department].
AB  - INTRODUCTION: Depression is especially frequent in the elderly. In addition to
      impairing quality of life, this disorder can affect the outcome of medical
      diseases. The objective is to analyze whether depressive disorders in elderly
      individuals attending an emergency room for medical complaints constitute a risk
      factor for admission. MATERIAL AND METHODS: All patients aged more than 74 years
      old attending the Emergency Department of the Hospital Universitario Central de
      Asturias who required comprehensive geriatric assessment from 2004 to 2005 were
      included in this study. Sociodemographic variables and data on functional,
      cognitive and emotional status before attendance at the emergency department were
      collected. A logistic regression analysis was performed to determine whether
      there was an independent association between depression and admission to the
      Geriatric Service. RESULTS: A total of 1016 patients (62.32% women) were
      evaluated. The mean age was 87.4 years. The Barthel index before admission to the
      emergency department was 71.8 (95% confidence interval [CI]: Depression was
      diagnosed in 17.4% of the patients (75.7% women). Of the whole sample, 721
      patients (71.0%) were admitted to a geriatric service, while 79.7% of patients
      with depression were admitted (p=0.002). After multivariate regression analysis
      adjusted by age, sex, marital status, institutionalization, living arrangements,
      Barthel index and cognitive status before admission, depression was independently
      associated with a greater risk for admission to a geriatric service (odds ratio:
      1.83, 95% CI: 1.20-2.78). CONCLUSIONS: Depression and mood disorders constitute
      an independent risk factor for admission to a geriatric service in patients aged
      more than 74 years assessed by comprehensive geriatric methodology in an
      emergency department.

PMID- 19864049
TI  - [Neurolymphomatosis: diagnosis of extension and assessment of response to
      treatment with PET-CT].
AB  - Neurolymphomatosis is a rare neurological manifestation of non-Hodgkin's lymphoma
      (NHL) and it may be its first and sole manifestation. Diagnosis is often
      difficult and nerve biopsy is generally required. However, this it is not always
      possible to perform or is not conclusive. We present the case of a 66-year-old
      woman diagnosed with giant B-cell NHL. After 6 cycles of chemotherapy, imaging
      and molecular biology techniques showed complete remission. At four months after
      treatment, the patient complained of low back pain of radicular distribution. CT
      and MRI imaging showed signs of lymphoproliferative activity of L5 and also
      lesions to thoracic nerve roots. A PET-CT was requested in order to complete the
      diagnosis and plan the treatment. Imaging confirmed the presence of tumor
      recurrence with neurolymphomatosis and also indicated lesions on the chest and
      abdominal level. Thus, it was decided to start a new line of chemotherapy,
      without performing the histological study through biopsy. This case illustrates
      the important role played by PET-CT imaging in neurolymphomatosis diagnosis. This
      technique can help the patient avoid more aggressive procedures, such as a
      biopsy, and can also be useful in the follow-up and assessment of the treatment
      response to NHL-diagnosed patients.

PMID- 19864050
TI  - Modelling multiple dispersion of radionuclides through the environment.
AB  - The migration of a contaminant through the environment is the result of the
      transport by a variety of biotic and abiotic carriers which move according to
      different dispersion mechanisms. Consequently, the patterns of the distribution
      of a pollutant in the environment cannot be ever explained on the basis of a
      single migration process or assuming that the concentrations of contaminant in
      the different kinds of carriers quickly reach the equilibrium condition. The
      present work discusses two examples (wash-off from catchments and transport
      through soils of radionuclides) that clearly demonstrate the inadequacy of
      "single dispersion" models to predict these patterns. On the contrary, models
      based on multiple dispersion can successfully simulate the particular features of
      the above mentioned processes. It was demonstrated that the time behaviour of
      radionuclide migration rates from catchment of different rivers vary within small
      ranges as a consequence of multiple dispersion. This result can be useful for the
      development of generic predictive models.

PMID- 19864051
TI  - Maternal infection rates after cesarean delivery by Pfannenstiel or Joel-Cohen
      incision: a multicenter surveillance study.
AB  - OBJECTIVE: Our purpose was to evaluate maternal nosocomial infection rates
      according to the incision technique used for caesarean delivery, in a routine
      surveillance study. STUDY DESIGN: This was a prospective study of 5123 cesarean
      deliveries (43.2% Joel-Cohen, 56.8% Pfannenstiel incisions) in 35 maternity units
      (Mater Sud Est network). Data on routine surveillance variables, operative
      duration, and three additional variables (manual removal of the placenta, uterine
      exteriorization, and/or cleaning of the parieto-colic gutter) were collected.
      Multiple logistic regression analysis was used to identify independent risk
      factors for infection. RESULTS: The overall nosocomial infection and endometritis
      rates were higher for the Joel-Cohen than Pfannenstiel incision (4.5% vs. 3.3%,
      0.8% vs. 0.3%, respectively). The higher rate of nosocomial infections with the
      Joel-Cohen incision was due to a greater proportion of patients presenting risk
      factors (i.e., emergency delivery, primary cesarean, blood loss > or =800 mL, no
      manual removal of the placenta and no uterine exteriorization). However, the Joel
      Cohen technique was an independent risk factor for endometritis. CONCLUSION: The
      Joel-Cohen technique is faster than the Pfannenstiel technique but is associated
      with a higher incidence of endometritis.

PMID- 19864052
TI  - Comparing hiking, mountain biking and horse riding impacts on vegetation and
      soils in Australia and the United States of America.
AB  - Hiking, horse riding and mountain biking are popular in protected areas in
      Australia and the United States of America. To help inform the often contentious
      deliberations about use of protected areas for these three types of activities,
      we review recreation ecology research in both countries. Many impacts on
      vegetation, soils and trails are similar for the three activities, although there
      can be differences in severity. Impacts include damage to existing trails, soil
      erosion, compaction and nutrification, changes in hydrology, trail widening,
      exposure of roots, rocks and bedrock. There can be damage to plants including
      reduction in vegetation height and biomass, changes in species composition,
      creation of informal trails and the spread of weeds and plant pathogens. Due to
      differences in evolutionary history, impacts on soil and vegetation can be
      greater in Australia than in the USA. There are specific social and biophysical
      impacts of horses such as those associated with manure and urine, grazing and the
      construction and use of tethering yards and fences. Mountain bike specific
      impacts include soil and vegetation damage from skidding and the construction of
      unauthorised trails, jumps, bridges and other trail technical features. There are
      gaps in the current research that should be filled by additional research: (1) on
      horse and mountain bike impacts to complement those on hiking. The methods used
      need to reflect patterns of actual usage and be suitable for robust statistical
      analysis; (2) that directly compares types and severity of impacts among
      activities; and (3) on the potential for each activity to contribute to the
      spread of weeds and plant pathogens. Additional research will assist managers and
      users of protected areas in understanding the relative impacts of these
      activities, and better ways to manage them. It may not quell the debates among
      users, managers and conservationists, but it will help put it on a more
      scientific footing.

PMID- 19864054
TI  - Studies on UV/NaOCl/TiO2/Sep photocatalysed degradation of Reactive Red 195.
AB  - The photocatalytic degradation of Reactive Red 195 (RR195) has been investigated
      in aqueous suspensions by using ultraviolet (UV), sodium hypochlorite (NaOCl) and
      TiO(2)/Sep nanoparticles together. To get the TiO(2)/Sep nanoparticle, the
      nanocrystalline TiO(2) anatase phase on sepiolite was obtained using a sufficient
      thermal treatment by gradually increasing the temperature from 300, 400 and 500
      degrees C for 3h. Then, TiO(2)/Sep materials were characterized using different
      spectral and technical structural analyses with scanning electron microscopy
      (SEM) and X-ray diffraction (XRD). The influence of pH, catalyst amount, oxidant
      and initial dye concentration was investigated in all the experiments. Maximum
      colour and chemical oxygen demand (COD) removal were 99.9% and 78% respectively,
      at a dye concentration of 250 mg L(-1), NaOCl dosage of 50.37 mM, 0.1 g L(-1)
      weight of TiO(2)/Sep and pH of 5.45 in 3h. In addition, the pseudo-first order
      model was applied and r(2) values were noted from 0.92 to 0.99.

PMID- 19864055
TI  - A critical review on the bio-removal of hazardous heavy metals from contaminated
      soils: issues, progress, eco-environmental concerns and opportunities.
AB  - Mechanism of four methods for removing hazardous heavy metal are detailed and
      compared-chemical/physical remediation, animal remediation, phytoremediation and
      microremediation with emphasis on bio-removal aspects. The latter two, namely the
      use of plants and microbes, are preferred because of their cost-effectiveness,
      environmental friendliness and fewer side effects. Also the obvious disadvantages
      of other alternatives are listed. In the future the application of genetic
      engineering or cell engineering to create an expected and ideal species would
      become popular and necessary. However, a concomitant and latent danger of genetic
      pollution is realized by a few persons. To cope with this potential harm, several
      suggestions are put forward including choosing self-pollinated plants, creating
      infertile polyploid species and carefully selecting easy-controlled microbe
      species. Bravely, the authors point out that current investigation of noncrop
      hyperaccumulators is of little significance in application. Pragmatic development
      in the future should be crop hyperaccumulators (newly termed as
      "cropaccumulators") by transgenic or symbiotic approach. Considering no effective
      plan has been put forward by others about concrete steps of applying a
      hyperaccumulator to practice, the authors bring forward a set of universal
      procedures, which is novel, tentative and adaptive to evaluate hyperaccumulators'
      feasibility before large-scale commercialization.

PMID- 19864056
TI  - Metallic iron for environmental remediation: learning from electrocoagulation.
AB  - The interpretation of processes yielding aqueous contaminant removal in the
      presence of elemental iron (e.g. in Fe(0)/H(2)O systems) is subject to numerous
      complications. Reductive transformations by Fe(0) and its primary corrosion
      products (Fe(II) and H/H(2)) as well as adsorption onto and co-precipitation with
      secondary and tertiary iron corrosion products (iron hydroxides, oxyhydroxides,
      and mixed valence Fe(II)/Fe(III) green rusts) are considered the main removal
      mechanisms on a case-to-case basis. Recent progress involving adsorption and co
      precipitation as fundamental contaminant removal mechanisms have faced a certain
      scepticism. This work shows that results from electrocoagulation (EC), using iron
      as sacrificial electrode, support the adsorption/co-precipitation concept. It is
      reiterated that despite a century of commercial use of EC, the scientific
      understanding of the complex chemical and physical processes involved is still
      incomplete.

PMID- 19864057
TI  - Kinetics determination of electrogenerated hydrogen peroxide (H2O2) using carbon
      fiber microelectrode in electroenzymatic degradation of phenolic compounds.
AB  - The kinetics of electrogenerated hydrogen peroxide (H(2)O(2)), which can activate
      peroxidases in an electroenzymatic process, was examined by an amperometric
      technique using a carbon fiber microelectrode that was modified by polyaniline
      (PAn) film and platinum particles. The electrogeneration of H(2)O(2) was found to
      be dependent on the pH and applied potential, and resulting in a variable current
      response of the carbon fiber microelectrode. The highest amount of H(2)O(2) was
      electrogenerated when 2.3 V was applied between the Pt/Ti anode and a reticulated
      vitreous carbon (RVC) cathode at pH 6.0, with a current response of 0.0190 microA
      min(-1). Phenol was completely degraded by the electroenzymatic reaction of the
      immobilized horseradish peroxidase (HRP), and the time required for the
      electrogeneration of H(2)O(2) increased according to the initial concentration of
      phenol. The degradation stoichiometric ratio between the electrogenerated
      H(2)O(2) and the aqueous phenol under HRP immobilized on RVC was found to be 1:1.

PMID- 19864058
TI  - Determination of Se(IV) in natural waters by adsorptive stripping voltammetry of
      5-nitropiazselenol.
AB  - The high tendency of 5-nitropiazselenol for self-accumulation on thin mercury
      film electrode was used innovatively for determination of Se(IV) in natural
      waters. 5-Nitropiazselenol was formed by reaction between Se(IV) and 4-nitro-1,2
      phenylenediamine in acidic solution and self-accumulation process was carried out
      directly from reaction media. The adsorbed 5-nitropiazselenol was stripped in HCl
      solution by DP cathodic potential scan. All parameters influencing the
      measurement were optimized and evaluated. Detection limit of this method is 0.06
      ng mL(-1). Interferences of various cations and anions were studied. The
      adsorption tendency of some other piazselenols made by some aromatic ortho
      diamines was also investigated. The problems arising from applying potential
      during accumulation process in natural waters analysis were discussed. This
      method was applied for determination of Se(IV) in natural waters collected from
      some internationally registrated lagoons south of Caspian Sea. The obtained
      results were compared with the results of ICP-AES and DPCSV after electrochemical
      preconcentration.

PMID- 19864059
TI  - Biosorption of heavy metals from industrial waste water by Geobacillus
      thermodenitrificans.
AB  - The metal binding capacity of the thermophilic bacteria Geobacillus
      thermodenitrificans isolated from Damodar river, India was assessed using
      synthetic metal solutions and industrial waste water. Biosorption preference of
      dead biomass of G. thermodenitrificans for the synthetic metal solutions was in
      the following order Fe(+3)>Cr(+3)>Co(+2)>Cu(+2)>Zn(+2)>Cd(+2)>Ag(+)>Pb(+2). It
      reduced the concentration of Fe(+3) (91.31%), Cr(+3) (80.80%), Co(+2) (79.71%),
      Cu(+2) (57.14%), Zn(+2) (55.14%), Cd(+2) (49.02%), Ag(+) (43.25%) and Pb(+2)
      (36.86%) at different optimum pH within 720 min. When this strain was applied in
      the industrial waste water biosorption preference was in the following order
      Fe(+3)>Cr(+3)>Cd(+2)>Pb(+2)>Cu(+2)>Co(+2)>Zn(+2)>Ag(+) and concentrations reduced
      up to 43.94% for Fe(+3), 39.2% for Cr(+3), 35.88% for Cd(+2), 18.22% for Pb(+2),
      13.03% for Cu(+2), 11.43% for Co(+2), 9.02% for Zn(+2) and 7.65% for Ag(+) within
      120 min.

PMID- 19864060
TI  - Enhanced photocatalytic activity for titanium dioxide by co-modifying with silica
      and fluorine.
AB  - F-Si-co-modified TiO(2) (FST) samples with different ratios of fluorine to
      titanium (R(F)) and silica to titanium (R(x)), were successfully synthesized by
      ultrasound-assisted hydrolysis. The structure and properties of the as-prepared
      codoped titania were characterized by means of XRD, TEM, XPS, BET, UV-Vis diffuse
      reflectance spectra and ESR. XRD analysis showed that Si and F atoms prevented
      phase transition of anatase to rutile and suppressed the growth of titania
      crystalline. ESR results showed that the concentration of the active species
      (.OH) on 1%-FST(R(x)=10%) was higher than that on other FST samples and P25
      titania. The improvement in photocatalytic activity relative to titania can be
      achieved by co-modifying fluorine and silica to fabricate FST composite material.
      The photocatalytic activity of FST powders for decomposition of methyl orange was
      affected by the content of fluorine and the content of silica. When the ratios of
      R(F) and R(x) were 1 and 10%, respectively, 1%-FST(R(x)=10%) shows the best among
      photocatalytic activity, which is much superior to P25 under UV-Vis irradiation.
      The possible reasons for the high photocatalytic activity of the FST powders were
      proposed in the paper. In addition, the stability of the FST powders in
      photocatalytic process was confirmed based on the XPS analysis.

PMID- 19864061
TI  - Removal of lead from aqueous solution with native and chemically modified
      corncobs.
AB  - In this study, corncobs biomass was utilized as an adsorbent to remove Pb(II)
      from aqueous solution. The adsorption behavior of Pb(II) was studied under
      different conditions, including solution pH, contact time and metal
      concentration. Ground corncobs were modified with CH(3)OH and NaOH to investigate
      the effect of chemical modification on Pb(II) binding capacity. Results showed
      that Pb(II) binding on the biomass is pH-dependent and the kinetics can be well
      described by the Lagergren-second-order model. The maximum Pb(II) binding
      capacity q(max) calculated from Langmuir isotherm was 0.0783 mmol/g. After base
      hydrolysis of the biomass, Pb(II) binding capacity increased from 0.0783 to
      0.2095 mmol/g (about 43.4 mg Pb/g). However, Pb(II) binding capacity on the
      esterified corncobs decreased greatly from 0.0783 to 0.0381 mmol/g. Fourier
      transform infrared spectroscopy (FTIR) analysis showed that hydroxyl and
      carboxylic (COO(-)) groups on the biomass play an important role in Pb(II)
      binding process. The X-ray photoelectron spectroscopy (XPS) data further
      indicated that lead is adsorbed as Pb(2+) and is attached to oxide groups on the
      biomass.

PMID- 19864062
TI  - Effects of surfactants and salt on Henry's constant of n-hexane.
AB  - n-Hexane biological removal is intrinsically limited by its hydrophobic nature
      and low bioavailability. The addition of surfactants could enhance the transport
      of volatile organic compounds (VOCs) and change the gas-liquid equilibrium of
      VOCs. In this paper, the effects of four surfactants, sodium dodecyl sulfate
      (SDS), cetyltrimethylammonium bromide (CTAB), tert-octylphenoxypoly-ethoxyethanol
      (Triton X-100), polyoxyethylene (20) sorbitan monooleate (Tween 80), and sodium
      nitrate on apparent Henry's constant of n-hexane in surfactant solutions were
      investigated. The apparent Henry's constants were significantly reduced when
      surfactants concentrations exceeded their critical micelle concentrations
      (cmc's). On a cmc basis, the anionic surfactant SDS was found to have the
      greatest effect on the apparent Henry's constant with CTAB succeeding, then
      followed by Triton X-100 and Tween 80. However, the apparent Henry's constant of
      n-hexane decreased even more rapidly when Triton X-100, a nonionic surfactant,
      was added than when the ionic surfactant of SDS or CTAB was applied under
      identical mass concentration and other conditions. These results suggest that
      Triton X-100 have the biggest solubilization of n-hexane among the four
      surfactants. Sodium nitrate slightly decreased the apparent Henry's constant of n
      hexane in surfactant solutions, and could be considered as a cosolvent in the
      surfactant-(n-hexane) solution. In addition, the relationship between apparent
      Henry's constant and surfactant concentration was further developed.

PMID- 19864063
TI  - Investigation on the toxic interaction of toluidine blue with calf thymus DNA.
AB  - The gene toxic interactions of toluidine blue (TB) with calf thymus DNA (ct-DNA)
      were examined in vitro with UV-visible absorption spectroscopy, fluorescence
      spectroscopy, fluorescence polarization and circular dichroism techniques. The
      experimental results showed that TB interacted with ct-DNA by two binding modes.
      At low TB concentrations, TB intercalated into the DNA base pairs. At higher TB
      concentrations, TB was attached to the negatively charged phosphate groups. For
      the intercalation binding mode and electrostatic binding mode, the binding
      constants were 1.76 x1 0(6)L mol(-1) and 6.18 x 10(5)L mol(-1) and the number of
      binding sites was 0.48 and 0.79, respectively. Circular dichroism results showed
      that the two binding modes had different effects on the ct-DNA conformation. At
      high dye concentrations, Z-form DNA appears, while at low TB concentrations, a B
      to A form transition is observed.

PMID- 19864064
TI  - Rapid Ti(III) reduction of perchlorate in the presence of beta-alanine: kinetics,
      pH effect, complex formation, and beta-alanine effect.
AB  - Ti(III) reduction of perchlorate might be a useful method for the treatment of
      highly perchlorate-contaminated water. Though the reaction rate was usually low,
      we observed that beta-alanine (HOOCCH(2)CH(2)NH(2)) could significantly promote
      the reaction. A complete (>99.9%) perchlorate removal was obtained in a solution
      containing [ClO(4)(-)]=1.0mM, [Ti(III)]=40 mM, and [beta-alanine]=120 mM after
      2.5h of reaction under 50 degrees C. The effects of both pH and complex formation
      on the reaction were then studied. The results showed that without beta-alanine
      the optimal pH was 2.3. When pH increased from 1.6 to 2.3, the reduction rate
      increased remarkably. In the pH range >2.3, however, the reduction was
      significantly inhibited, attributed to the formation of Ti(III) precipitate. The
      presence of beta-alanine at a molar ratio of [beta-alanine]:[Ti(III)]=3:1
      significantly increased the reduction rate of perchlorate even at near neutral
      pH. This is because beta-alanine formed complexes with Ti(III), which greatly
      improved the total soluble [Ti(III)] in the pH range between 3.5 and 6. The
      findings may lead to the development of rapid treatment methods for intermittent
      and small stream of highly perchlorate-contaminated water, which are resulted
      from the manufacturing, storage, handling, use and/or disposal of large
      quantities of perchlorate salts.

PMID- 19864065
TI  - Complete electrochemical dechlorination of chlorobenzenes in the presence of
      various arene mediators.
AB  - Electrochemical dechlorination of chlorobenzenes in the presence of various arene
      mediators such as naphthalene, biphenyl, phenanthrene, anthracene, and pyrene,
      was studied. The amount of mediator required was able to be reduced to 0.01
      equiv. for all mediators except for anthracene, with the complete dechlorination
      of mono-, 1,3-di- and 1,2,4-trichlorobenzene still achieved. This catalytic
      amount of mediator plays an important role in accelerating the dechlorination
      through the rapid formation of radical anions prior to reduction of the
      chlorobenzenes.

PMID- 19864066
TI  - Sleep restriction attenuates amplitudes and attentional modulation of pain
      related evoked potentials, but augments pain ratings in healthy volunteers.
AB  - The experiment investigated the impact of sleep restriction on pain perception
      and related evoked potential correlates (laser-evoked potentials, LEPs). Ten
      healthy subjects with good sleep quality were investigated in the morning twice,
      once after habitual sleep and once after partial sleep restriction. Additionally,
      we studied the impact of attentional focussing on pain and LEPs by directing
      attention to (intensity discrimination) or away from the stimulus (mental
      arithmetic). Laser stimuli directed to the hand dorsum were rated as 30% more
      painful after sleep restriction (49+/-7 mm) than after a night of habitual sleep
      (38+/-7 mm). A significant interaction between attentional focus and sleep
      condition suggested that attentional focusing was less distinctive under sleep
      restriction. Intensity discrimination was preserved. In contrast, the amplitude
      of the early parasylvian N1 of LEPs was significantly smaller after a night of
      partial sleep restriction (-36%, p<0.05). Likewise, the amplitude of the vertex
      N2-P2 was significantly reduced (-34%, p<0.01); also attentional modulation of
      the N2-P2 was reduced. Thus, objective (LEPs) and subjective (pain ratings)
      parameters of nociceptive processing were differentially modulated by partial
      sleep restriction. We propose, that sleep reduction leads to an impairment of
      activation in the ascending pathway (leading to reduced LEPs). In
      contradistinction, pain perception was boosted, which we attribute to lack of
      pain control distinct from classical descending inhibition, and thus not
      affecting the projection pathway. Sleep-restricted subjects exhibit reduced
      attentional modulation of pain stimuli and may thus have difficulties to readily
      attend to or disengage from pain.

PMID- 19864067
TI  - Selection of an ivermectin-resistant strain of Rhipicephalus microplus (Acari:
      Ixodidae) in Brazil.
AB  - Resistance to ivermectin (IVM) in field populations of Rhipicephalus microplus of
      Brazil has been observed since 2001. In this work, four selection methods
      (infestations with: (1) IVM-treated larvae; (2) larvae from IVM-treated adult
      female ticks; (3) larvae from IVM-treated adult female ticks on an IVM-treated
      host; and (4) larvae obtained from IVM-treated females that produced eggs with a
      high eclosion rate) were used on a field population with an initial ivermectin
      (IVM) resistance ratio at LC50 (RR50) of 1.37 with the objective to obtain
      experimentally a highly-resistant strain. After ten generations, using these
      methods combined, the final RR50 was 8.06. This work shows for the first time
      that it was possible to increase IVM resistance in R. microplus in laboratory
      conditions. The establishment of a drug resistant R. microplus strain is a
      fundamental first step for further research into the mechanisms of ivermectin
      resistance in R. microplus and potentially methods to control this resistance.

PMID- 19864068
TI  - A wide diversity of zoonotic intestinal parasites infects urban and rural dogs in
      Neuquen, Patagonia, Argentina.
AB  - The presence of parasites was investigated by the examination of 1944 dog faecal
      samples collected from urban (n=646) and rural (n=1298) areas of the province of
      Neuquen, Patagonia, Argentina. Parasitic agents (PA) were found in 37.86% of
      samples. A total of 15 different PA were detected, including Toxocara canis
      (16.35%), Taenia spp./Echinococcus spp. (12.65%), Trichurisvulpis (6.06%),
      Giardia spp. (1.29%), Toxascaris leonina (0.56%), Ancylostomacaninum (0.41%),
      Dipylidium caninum (0.31%), Diphyllobothrium spp. (0.10%), among others. Several
      of these PA are recognized as zoonotic agents. Therefore, the results of this
      investigation revealed that local population is exposed to a broad spectrum of
      zoonotic parasites by means of environmental contamination with dog faeces.
      Prevalence of PA was slightly higher in rural (40.06%) than in urban (33.44%)
      locations. Distribution of groups of PA (cestodes, nematodes, and protozoa)
      showed statistical differences between both habitats. Prevalence of cestodes
      (18.18%) and protozoa (11.86%) was significantly higher in the rural environment
      than in urban areas and nematodes (29.10%) were more frequent in urban locations.
      Infection of dogs with Linguatula serrata and Cryptosporidium sp. was
      demonstrated for the first time in Neuquen. Rural dogs of the study area are
      under hydatic disease control program, which includes treatment with praziquantel
      every 6 weeks; thus, the finding of high level of cestode infection in these
      areas is of great relevance. The epidemiology of zoonotic parasitic infections in
      urban and rural dogs showed different patterns and, in consequence, different
      control measurements should be applied in each location.

PMID- 19864069
TI  - Trypanosoma evansi infection in mainland Spain.
AB  - An outbreak of Trypanosoma evansi infection that occurred in mainland Spain is
      described. The outbreak occurred on an equine and camel farm to which dromedary
      camels from an infected area of the Canary Islands had recently been introduced.
      One of these camels developed clinical signs and T. evansi was discovered in a
      blood smear examination. The herd was evaluated in order to determine the extent
      of the disease. The results showed that 76% of the camels, 35% of the donkeys and
      2% of the horses were affected. The animals were isolated and treated using
      Cymelarsan((R)) (0.5mg/kg). After treatment, three blood analysis using
      parasitological methods revealed negative results. This is the first T. evansi
      outbreak to have occurred in mainland Spain and the second in mainland Europe,
      both occurring after the introduction of dromedary camels from the Canary
      Islands.

PMID- 19864070
TI  - An objective long-term evaluation of Integra (a dermal skin substitute) and split
      thickness skin grafts, in acute burns and reconstructive surgery.
AB  - INTRODUCTION: The field of wound healing and tissue repair has advanced rapidly
      in the last decade, with this there is an increasing emphasis on the importance
      of the functional and cosmetic outcomes following injury. Integra artificial skin
      is the most widely used synthetic skin substitute and is reported to have better
      outcomes in relation to the appearance and elasticity when compared to split
      thickness skin grafting (SSG). A review of the literature reveals very few trials
      that are based on an objective evaluation of Integra treated scars as compared to
      SSGs. This research aimed to provide objective data on the long-term outcome of
      Integra. METHOD: All adult patients from the Welsh Burns Centre who had been
      successfully treated with Integra+/-SSG were invited to attend a clinic for a
      follow up provided they had been healed for greater than one year. The hypothesis
      that Integra scars are more pliable than skin grafts was tested objectively using
      the Cutometer, a suction device which measures skin elasticity. RESULTS: Of the
      13 patients eligible, six were available for assessment. The results of this
      study suggest that Integra treated sites correlate well with normal skin as
      measured by the Cutometer. This was statistically significant for the parameters
      Ur/Ue (elastic function) and Ur/Uf (gross elasticity). On the other hand there
      was no correlation seen between the patients SSG sites and the patient's normal
      skin. CONCLUSION: With advances in medicine we are increasingly able to modulate
      wound healing and the resultant scars. In order to assess new and often costly
      treatments the need for objective scar measurement tools have become apparent.
      Integra has been advocated to improve scarring from injury. However, there have
      been few studies to evaluate the long-term outcome of Integra as compared to
      traditional methods such as SSG. In the past scar evaluation has been based on
      subjective scores by patients and clinicians. Now the mechanical properties of
      the skin can be evaluated using simple bioengineering methods such as the
      Cutometer Suction Device. Using this device our study has objectively
      demonstrated that the elastic properties of areas treated with Integra is
      comparable to normal skin.

PMID- 19864071
TI  - Cryogenic burns from intentional use of aerosol spray in children: an emerging
      phenomenon.

PMID- 19864072
TI  - Use of colistin in treating multi-resistant Gram-negative organisms in a
      specialised burns unit.
AB  - Patients with burns are at an increased risk of infection which can affect their
      outcome-duration of hospital stay, intensive care requirements, organ support,
      inotrope requirements, renal replacement therapy, ventilatory requirements and
      overall mortality. Our study aimed to evaluate the use of colistin in our burns
      intensive care unit (ICU) in treating multi-resistant Gram-negative infections.
      This was a retrospective study carried out in a regional referral centre for
      burns and plastics, Chelmsford, UK. We looked at data from patients admitted to
      our intensive care over a two-year period from November 2003 to November 2005.
      All patients who received colistin were included in the study. Admission data
      included demographic data and burn data, other relevant medical history, and
      blood results. We also recorded: length of ICU stay, ultimate outcome, total dose
      of colistin, repeated doses, and mode of drug delivery, organ support, organisms
      grown and their resistance. Response to colistin was judged by improvement in
      clinical status, decrease in white blood cell count (WCC) and inflammatory
      markers and no growth on cultures. The data were subjected to non-parametric
      Wilcoxon Signed Rank Test using SPSS version 14. Twenty-nine patients were
      included in the study all of whom received colistin in one form or the other. The
      average total dose of colistin was 69 million units (range 1-268). Of these, 17
      patients survived (58.6%) and 12 died (41.4%). Twenty patients improved (69%) and
      9 did not improve (31%) after administration of colistin. We also compared
      creatinine levels on admission and post colistin. We used non-parametric Wilcoxon
      Signed Rank test which showed no difference in the two groups (p=0.38). We found
      colistin to be safe and effective in treating multi-resistant Gram-negative
      infections in burns patients and we did not see any statistically significant
      impairment of renal function.

PMID- 19864073
TI  - Chemical burns: pathophysiology and treatment.
AB  - Chemical burns continue to pose a variety of dilemmas to the clinician managing
      such cases. Assessment of burn depth is often difficult and the decision whether
      to excise the wound early is not always clear-cut. In this updated review, common
      agents are classified and the basic principles of management and specific
      recommendations are examined. The complications arising from exposure to these
      chemicals and the supportive measures needed during treatment are also described.

PMID- 19864074
TI  - A retrospective review of burn dressings on a porcine burn model.
AB  - This is a study to compare wound healing among three types of dressings on a
      porcine model with deep-dermal-partial-thickness burns. The burns in this study
      were from eight animal trials conducted in the past for other purposes and only
      burns with a uniform pale appearance that had served as controls in original
      experiments were selected. In total, there were 57 burns in 33 pigs, using one of
      following three dressings: Acticoat (Silver) (3 trials), Jelonet (Gauze) (3
      trials), and Solosite Gel/Jelonet (Gel/Gauze) (2 trials). The wound healing
      assessments included wound re-epithelialisation during a 6-week period, clinical
      and histological scar assessments at week 6 after burn. Of all wound healing/scar
      assessments, only re-epithelialisation showed statistical difference between
      dressings. Earlier re-epithelialisation was observed in Gel/Gauze dressings
      compared to Silver and/or Gauze dressings. However, this study revealed huge
      variation in wound healing outcome between 3 trials within both Silver and/or
      Gauze dressings, supported by significant differences on re-epithelialisation,
      clinical and histological scar measurements. In addition, it was found that
      larger animals healed better than smaller ones, based on weights from 21 pigs. Of
      all dressings, Silver delivers the best protection for wound
      colonization/infection. Wound colonization/infection was found to confine wound
      healing and lead to thinner RND in scars. From this study, we cannot find enough
      evidence to suggest the beneficial effect of one dressing(s) over others on burn
      wound healing outcome on a porcine model with small deep-dermal-partial-thickness
      burns with a relative small sample size.

PMID- 19864075
TI  - Modic type III lesions and Schmorl's nodes are the same pathological changes?
AB  - INTRODUCTION: Degenerative disc disease (DDD) is a major health problem
      worldwide. Both Modic lesions and Schmorl's nodes are considered to correlate
      with DDD such as low back pain. Modic lesions are the changes of degenerative
      vertebral endplate and adjacent bone marrow observed on magnetic resonance
      imaging and are divided into three types. Modic type III lesions are thought to
      represent extensive subchondral bone sclerosis within the bone marrow of adjacent
      endplate. The pathological performance of Schmorl's nodes is cystic lesions
      around indistinct sclerotic margins and beneath the cartilaginous endplate.
      Coincidently, there are many similarities between Modic type III lesions and
      Schmorl's nodes including pathological appearances, pathogenetic location and
      related diseases. HYPOTHESIS: We hypothesize that Modic type III lesions and
      Schmorl's nodes are the same pathological changes, and Modic type III lesions may
      be the quiescent or incipient pathology phrase of Schmorl's nodes. The clinical
      symptoms of DDD are also accompanied by emergence of these pathological changes.
      TESTING: A longitudinal study could be used to test this hypothesis. We could
      measure and analyze whether Modic type III lesions have increased in size or
      evolved into Schmorl's nodes as time goes on. SIGNIFICANCE: This hypothesis
      explains the possible pathologic process of Modic type III lesions and Schmorl's
      nodes. If the hypothesis were conformed, Modic type III lesions and Schmorl's
      nodes will be rediscovered, which provides the new basis for the clinical
      treatment of DDD. In additions, this hypothesis also has crucial significances
      for the classification of Modic lesions.

PMID- 19864076
TI  - Why does diabetes offer protective effects against prostate cancer? The possible
      role of its microvascular complications.
AB  - Prostate cancer (CaP) is one of the most common types of cancer among men and the
      second leading cause of cancer-related death in western countries. The risk
      factors for CaP are age, race/ethnicity, family history and diet. It is
      interesting that epidemiologic evidence suggests a history of diabetes mellitus
      (DM) is related to a decreased CaP risk. The cause of this association remains
      largely unknown. DM is a group of metabolic diseases characterized by
      hyperglycemia and insulin resistance. It is commonly associated with
      microvascular complications including diabetic retinopathy, nephropathy and
      neuropathy. The typical histological changes of microvascular lesions are
      capillary basement membrane thickening, capillary occlusion and degeneration,
      eventually capillary dysfunction and organ ischemia. Therefore, we hypothesize
      that DM might induce local microvascular dysfunction and prostate ischemia, which
      prevent initiation and development of CaP. Currently, numerous studies showing
      effect of anti-angiogenesis therapy on CaP strongly support our hypothesis.

PMID- 19864077
TI  - Quality of life after stereotactic radiotherapy for stage I non-small-cell lung
      cancer.
AB  - PURPOSE: To determine the impact of stereotactic radiotherapy on the quality of
      life of patients with inoperable early-stage non-small-cell lung cancer (NSCLC).
      Overall survival, local tumor control, and toxicity were also evaluated in this
      prospective study. METHODS AND MATERIALS: From January 2006 to February 2008,
      quality of life, overall survival, and local tumor control were assessed in 39
      patients with pathologically confirmed T1 to 2N0M0 NSCLC. These patients were
      treated with stereotactic radiotherapy. The European Organization for Research
      and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the QLQ
      LC13 lung cancer-specific questionnaire were used to investigate changes in
      quality of life. Assessments were done before treatment, at 3 weeks, and at 2, 4,
      6, 9, and 12 months after treatment, until death or progressive disease. Toxicity
      was evaluated using common terminology criteria for adverse events version 3.0.
      RESULTS: Emotional functioning improved significantly after treatment. Other
      function scores and QLQ C30 and QLQ LC13 lung symptoms (such as dyspnea and
      coughing) showed no significant changes. The overall 2-year survival rate was
      62%. After a median follow-up of 17 months, 1 patient had a local recurrence
      (3%). No grade 4 or 5 treatment-related toxicity occurred. Grade 3 toxicity
      consisted of thoracic pain, which occurred in 1 patient within 4 months of
      treatment, while it occurred thereafter in 2 patients. CONCLUSIONS: Quality of
      life was maintained, and emotional functioning improved significantly after
      stereotactic radiotherapy for stage I NSCLC, while survival was acceptable, local
      tumor control was high, and toxicity was low.

PMID- 19864078
TI  - Neoadjuvant chemoradiation with paclitaxel/carboplatin for selected Stage III non
      small-cell lung cancer: long-term results of a trimodality Phase II protocol.
AB  - PURPOSE: To evaluate, in a Phase II trial conducted August 1998 through January
      2001, the efficacy of neoadjuvant chemotherapy followed by chemoradiotherapy and
      definitive surgery in patients with locally advanced non-small-cell lung cancer
      (LA-NSCLC), Stages IIIA bulky and selected Stage IIIB. PATIENTS AND METHODS:
      Staging of LA-NSCLC included computed tomography of cranium, thorax, and abdomen,
      whole-body positron emission tomography, and video mediastinoscopy. Induction
      chemotherapy with weekly paclitaxel and carboplatin was followed by
      hyperfractionated accelerated thoracic radiotherapy (45 Gy) with simultaneous
      weekly paclitaxel and carboplatin. Four to six weeks after completion of
      induction therapy, restaging and resection of primary tumor and lymph nodes was
      intended. RESULTS: A total of 59 consecutive patients were enrolled, 25% with
      Stage IIIA bulky disease, 65% with Stage IIIB, and 10% with Stage IV (excluded
      from further analysis). Forty-one patients completed induction therapy; in 52.4%
      a functional (positron emission tomography) downstaging was proven. Thirty-two
      patients (59.3%) underwent complete tumor resection, and 5 patients had an
      exploratory thoracotomy only. Histopathologic downstaging was proven in 59.4% and
      complete response in 21.9%. Hospital mortality was 5.4%. Median duration of
      follow-up for living patients was 62.1 months. Overall median survival was 22.6
      months, 58.2 months for completely resected patients. During induction
      chemotherapy, Grade 3/4 granulocytopenia occurred in 8% of patients; the most
      common Grade 3/4 toxicity of chemoradiation was esophagitis, in 26.4% of
      patients. CONCLUSIONS: Induction paclitaxel/carboplatin with hyperfractionated
      accelerated chemoradiotherapy followed by complete tumor resection demonstrates
      high efficacy in LA-NSCLC and offers a promising chance of long-term survival.

PMID- 19864079
TI  - Factors influencing neurocognitive outcomes in young patients with benign and low
      grade brain tumors treated with stereotactic conformal radiotherapy.
AB  - PURPOSE: To present the effect of radiotherapy doses to different volumes of
      normal structures on neurocognitive outcomes in young patients with benign and
      low-grade brain tumors treated prospectively with stereotactic conformal
      radiotherapy (SCRT). METHODS AND MATERIALS: Twenty-eight patients (median age, 13
      years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar
      astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated
      with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective
      neuropsychological assessments were done at baseline before RT and at subsequent
      follow-up examinations. The change in intelligence quotient (IQ) scores was
      correlated with various factors, including dose-volume to normal structures.
      RESULTS: Although the overall mean full-scale IQ (FSIQ) at baseline before RT
      remained unchanged at 2-year follow-up after SCRT, one third of patients did show
      a >10% decline in FSIQ as compared with baseline. Logistic regression analysis
      demonstrated that patients aged <15 years had a significantly higher chance of
      developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03).
      Dosimetric comparison in patients showing a >10% decline vs. patients showing a
      <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of
      the left temporal lobe were the ones to show a significant drop in FSIQ (p =
      0.048). Radiotherapy doses to other normal structures, including supratentorial
      brain, right temporal lobe, and frontal lobes, did not reveal any significant
      correlation. CONCLUSION: Our prospectively collected dosimetric data show younger
      age and radiotherapy doses to left temporal lobe to be predictors of
      neurocognitive decline, and may well be used as possible dose constraints for
      high-precision radiotherapy planning.

PMID- 19864080
TI  - Brachytherapy as part of the multidisciplinary treatment of childhood
      rhabdomyosarcomas of the orbit.
AB  - INTRODUCTION: Rhabdomyosarcomas in the orbit form a major challenge in terms of
      cure without severe side effects in childhood cancer. Our specifically developed
      approach consists of applying brachytherapy to the tumor area using a mold.
      Analysis of its results for 20 patients was performed. METHODS AND MATERIALS:
      Thirteen patients were referred for brachytherapy if complete remission was not
      reached after chemotherapy (Group I) and 7 in case of relapse (Group II). In
      total, 20 patients were treated between 1991 and 2007. Four were female and 16
      male; their ages varied from 1.1 to 16.5 years, with an average of 8.5 years.
      After macroscopically radical tumor resection, molds with holes drilled to hold
      flexible catheters were placed into the orbit. The dose to the clinical target
      volume was 40-50 Gy. RESULTS: Three patients of Group I and 1 patient of Group II
      developed local recurrence and underwent exenteration. The progression-free
      survival in Group I is 71.9% (95% CI 0.44-1.0), in Group II 85.7% (95% CI 0.60
      1.0), the overall 5-year survival rate of the entire group is 92% (95% CI 0.76
      1.0). During treatment, no serious side effects were observed. The late
      complications encountered in this series were cataract in 2 patients, 1 of whom
      also developed mild retinopathy. Two patients with ptosis needed surgical
      correction. No facial asymmetries or bone growth anomalies were observed.
      CONCLUSIONS: This entire procedure of brachytherapy with a mold offers a tailor
      made treatment for orbital rhabdomyosarcomas with only few signs of late
      toxicity.

PMID- 19864081
TI  - Optimal treatment for intracranial germinoma: can we lower radiation dose without
      chemotherapy?
AB  - PURPOSE: To review the effectiveness of reduced-dose and restricted-volume
      radiation-only therapy in the treatment of intracranial germinoma and to assess
      the feasibility of reducing or eliminating the use of chemotherapy. METHODS AND
      MATERIALS: Between January 1996 and March 2007, a retrospective analysis was
      performed that included 38 patients who received either reduced radiation alone
      (30 Gy for 26 patients) or reduced radiation with chemotherapy (n = 12 patients).
      All 38 patients received extended focal (including whole-ventricle) irradiation
      and were followed up until February 2008. Overall survival (OS) and relapse-free
      survival (RFS) rates were calculated. Variables associated with survival were
      evaluated by univariate Cox proportional hazards regression. RESULTS: Median
      follow-up was 62.4 months (range, 10.1-142.5 months). The total 5-year OS rate
      was 93.7%. The 5-year OS and RFS rates for patients receiving radiation only were
      100% and 96.2%, respectively. The rates for those receiving radiation plus
      chemotherapy were 83.3 % and 91.7%, respectively (not statistically significant).
      No predictive factor was significantly associated with the OS or RFS rate.
      Chemotherapy had no significant effect on survival but was associated with a
      higher incidence of treatment-related toxicity. CONCLUSIONS: A further decrease
      in the radiation dose to 30 Gy with whole-ventricle irradiation is sufficient to
      treat selected patients with intracranial germinoma. Wide-field irradiation or
      chemotherapy should be avoided as these methods are unnecessary. Thus, reduction
      of the radiation dose to 30 Gy may be feasible, even without chemotherapy.

PMID- 19864082
TI  - Radiation with or without 6 months of androgen suppression therapy in
      intermediate- and high-risk clinically localized prostate cancer: a
      postrandomization analysis by risk group.
AB  - PURPOSE: Six months of androgen suppression therapy (AST) plus radiation (RT)
      prolongs survival vs. RT alone in men with unfavorable risk localized prostate
      cancer (PCa), but it is unknown if this benefit applies to all risk subgroups
      and, in particular, the intermediate-risk group. METHODS AND MATERIALS: Among 206
      men with stages T1b to T2b PCa and either a prostate-specific antigen level of
      >10 or a Gleason score of > or =7 or MRI evidence of T3 disease randomized to
      receive 70 Gy of RT with or without 6 months of AST, Cox multivariable analysis
      was used to assess the impact of AST on overall survival in intermediate- and
      high-risk localized PCa, adjusting for age, Adult Comorbidity Evaluation 27
      comorbidity score, interaction between comorbidity and treatment, and known
      prognostic factors. Survival estimates were compared using a two-sided log-rank
      test. RESULTS: After an 8.2-year median follow-up, 74 men died. Compared to
      treatment with AST plus RT, treatment with RT alone was associated with an
      increased risk of death in intermediate-risk (adjusted hazard ratio, 3.0 [95%
      confidence interval, 1.3-7.2]; p = 0.01) and high-risk PCa (adjusted hazard
      ratio, 3.3 [95% confidence interval, 0.94-11.3]; p = 0.06). The survival benefit
      of adding AST was restricted to men with no or mild comorbidity in both the
      intermediate-risk (90.9% vs. 85.8% survival, respectively, at 7 years for AST
      plus RT vs. RT alone; p = 0.009) and high-risk (88.9% vs. 51.2% survival,
      respectively, at 7 years for AST plus RT vs. RT alone; p = 0.007) subgroups.
      CONCLUSIONS: In men with localized PCa who have no or mild comorbidity, adding 6
      months of AST to RT was associated with improved survival for those with both
      intermediate-risk and high-risk disease, but in men with moderate to severe
      comorbidity, no benefit was observed in either risk group.

PMID- 19864083
TI  - Unilateral prostate cancer cannot be accurately predicted in low-risk patients.
AB  - PURPOSE: Hemiablative therapy (HAT) is increasing in popularity for treatment of
      patients with low-risk prostate cancer (PCa). The validity of this therapeutic
      modality, which exclusively treats PCa within a single prostate lobe, rests on
      accurate staging. We tested the accuracy of unilaterally unremarkable biopsy
      findings in cases of low-risk PCa patients who are potential candidates for HAT.
      METHODS AND MATERIALS: The study population consisted of 243 men with clinical
      stage <or=T2a, a prostate-specific antigen (PSA) concentration of <10 ng/ml, a
      biopsy-proven Gleason sum of <or=6, and a maximum of 2 ipsilateral positive
      biopsy results out of 10 or more cores. All men underwent a radical
      prostatectomy, and pathology stage was used as the gold standard. Univariable and
      multivariable logistic regression models were tested for significant predictors
      of unilateral, organ-confined PCa. These predictors consisted of PSA, % fPSA
      (defined as the quotient of free [uncomplexed] PSA divided by the total PSA),
      clinical stage (T2a vs. T1c), gland volume, and number of positive biopsy cores
      (2 vs. 1). RESULTS: Despite unilateral stage at biopsy, bilateral or even non
      organ-confined PCa was reported in 64% of all patients. In multivariable
      analyses, no variable could clearly and independently predict the presence of
      unilateral PCa. This was reflected in an overall accuracy of 58% (95% confidence
      interval, 50.6-65.8%). CONCLUSIONS: Two-thirds of patients with unilateral low
      risk PCa, confirmed by clinical stage and biopsy findings, have bilateral or non
      organ-confined PCa at radical prostatectomy. This alarming finding questions the
      safety and validity of HAT.

PMID- 19864084
TI  - [HPV detection and typing by INNO-LiPA assay on liquid cytology media Easyfix
      Labonord after extraction QIAamp DNA Blood Mini Kit Qiagen and Nuclisens easyMAG
      Biomerieux].
AB  - OBJECTIVES: The objective of this study is to validate the use of test INNO-LIPA
      HPV Genotyping Extra (Innogenetics) on liquid cytology media EasyFix Labonord by
      comparing the extraction kit QIAamp DNA Blood Mini Kit (Qiagen) and an automated
      method, Nuclisens easyMAG (Biomerieux). METHODS: Thirty-two samples were typed by
      the technique Hybrid Capture 2 (HC2) Digene (Qiagen). DNA was extracted through
      manual or automated extraction and quality controlled PCR "HLA". Typing was
      performed with the INNO-LIPA test. A nested PCR followed by sequencing was used
      to compare different results. RESULTS: Similar results were found for the two
      types of extraction, with an increase of sensitivity after automated extraction.
      Among the nine patients with a negative result with the HC2 test, seven had a
      negative result in INNO-LIPA and two a positive result (one untypable and one
      HPV66). On the 23 patients with a positive result with the HC2 test, 17 are
      consistent results. The six discordant results include one negative, one HPV54,
      two untypable HPV and two HPV53. The overall concordance between the HC2 and INNO
      LIPA tests is 81% with a kappa test of 0.79. CONCLUSION: Coupled with an
      automated extraction, the test INNO-LIPA confirmed its high sensitivity for
      detecting and typing HPV in the EasyFix media Labonord, especially in the
      presence of multiple genotypes. This typing systematic approach is becoming
      increasingly relevant in the context of HPV vaccination.

PMID- 19864085
TI  - [Evolution of Enterobacteriaceae resistance to antibiotics in Reunion Island:
      emergence of extended-spectrum beta-lactamases].
AB  - AIM OF THE STUDY: The antibiotic resistance of enterobacteriacae knows a
      worldwide worrying evolution with an increase of the extended spectrum
      betalactamases (ESBL) that spread into the community. Few publications describe
      this problem in the Indian Ocean area. The aim of this study is first to identify
      in Felix Guyon Hospital (Reunion Island) the emergent antibiotics resistance for
      enterobacteriaceae between 1997/1998 and 2006/2007 periods, at second, to update
      the prophylactic and therapeutic measures for handling the risk linked to
      multiresistant enterobacteriaceae in our hospital and third, to assess the risk
      in Reunion Island and especially at the community level. METHODS: The antibiotic
      susceptibility of 7814 enterobacteriaceae strains collected among patients,
      during 1997/1998 and 2006/2007 periods, were analysed as well as the consumption
      of the third generation cephalosporins, imipenem and fluoroquinolones. RESULTS:
      Within a span of time of 10 years, an important increase (+57 %) of the
      resistance prevalence of enterobacteriaceae is observed. The resistance by the
      ESBL production mechanism is predominant especially for Enterobacter cloacae and
      Escherichia coli. An important use of broad spectrum antibiotics is correlated
      with this resistance evolution. CONCLUSION: The emergence of ESBL-producing
      enterobacteriaceae in our hospital is impairing both therapeutic and health care.
      It requires a much better control of antibiotics prescriptions and therefore, an
      important multidisciplinary implication. A proof molecular analysis would allow
      to evaluate the risk more precisely, especially at the community level.

PMID- 19864086
TI  - [Epidemiology of Enterobacteriaceae producing extended-spectrum beta-lactamase in
      Grasse Hospital (2005-2008)].
AB  - BACKGROUND: The CASFM 2008 don't recommend to search a BLSE for
      Enterobacteriaceae (E-BLSE) having a aac(6'). So we wanted to take stock of
      antibiotics co-resistances in our laboratory for these bacteria. We look for the
      aminoglycosides and quinolones FQ. METHODS: We studies all E-BLSE isolated in our
      laboratory from the 1(st) six month of 2005 to the 1st six month of 2008. Only
      one isolate per patient were included in this study. For each bacterial strain
      aminoglycosides and quinolones FQ (nalidixic acid [NA], ciprofloxacin [CIP]) were
      tested. RESULTS: A total of 124 E-BLSE isolates were studied. Escherichia coli
      increases (12 to 86%) and Enterobacter spp decreases (33 to 5%). We can note an
      increase of sensibles strains (6 to 23%).The mainly resistance associated is the
      FQ resistance (CIP: 88 to 68%). The resistance of aminoglycosides is almost
      associated with the NA resistance (59 to 36%). The presence of aac(6') decreases
      (29 to 1%). CONCLUSION: BLSE are mainly produced by Escherichia coli and
      antibiotics coresistances change: increase sensibles strains, supremacy of FQ
      resistance and decrease of the aac(6').This results can have repercussions on
      antibiotherapy.

PMID- 19864088
TI  - Functional relationships among intrafollicular insulin-like growth factor 1,
      circulatory gonadotropins, and development of the dominant follicle in mares.
AB  - The functional relationships among intrafollicular free insulin-like growth
      factor 1 (IGF1), circulatory gonadotropins, and development of the dominant
      follicle were studied in 40 mares in two experiments. A GnRH antagonist (Acyline)
      was given i.m. at the expected beginning of follicular deviation (largest
      follicle or F1> or =20mm; Day 0) alone (Acyline group) or in combination with
      intrafollicular treatment of F1 with rhIGF1 (Acyline/IGF1 group). In Experiment
      1, blood samples, follicular-fluid samples, and diameter of F1 were taken on Days
      1 and 2. In Experiment 2, daily follicular diameter and blood samples were taken
      from Day 0 to ovulation. The GnRH antagonist induced a 50% decrease in
      circulatory FSH concentrations for 1 d and in LH for 2 d. In Experiment 1,
      control and Acyline/IGF1 groups had greater intrafollicular free IGF1 (P<0.05)
      and inhibin-A concentrations (P<0.08) than the Acyline group. The intrafollicular
      concentration of estradiol on Day 2 was greater (P<0.05) in the control group
      than in the Acyline and the Acyline/IGF1 groups. In Experiment 2, a decrease in
      diameter of F1 in the Acyline group was followed by a new follicular wave. All
      IGF-treated follicles grew and ovulated. Results indicated that the increase in
      intrafollicular free IGF1 observed in F1 in association with deviation is
      gonadotropin dependent. During the period of lesser gonadotropin concentrations
      from Acyline treatment, intrafollicular IGF1 stimulated follicular growth and
      inhibin concentrations, but not intrafollicular estradiol production.

PMID- 19864087
TI  - [Prophylaxis use of posaconazole (P) in an hemato-oncology unit: a retrospective
      study].
AB  - OBJECTIVE OF THIS STUDY: The mortality level of leucemic patient's fungal
      infections can reach 70%. Antifungal prophylaxis posaconazole (P) is used during
      severe and prolonged neutropenia resulting from chemotherapy for acute
      myelogenous leukemia (AML), myelodysplastic syndrome and after autologous
      transplant. PATIENTS AND METHODS: We realized a retrospective study in order to
      assess the efficiency of P. Oral prophylaxy dosage is 200mg every eight hours to
      beginning before presumed neutropenia. Treatment failure was defined as the
      occurrence of proven/probable invasive fungal infections (IFI), receipt of any
      other systemic antifungal agent for suspected IFI or for impossible swallowing
      and the occurrence of adverse event. The objective is to note down the incidence
      of proven/probable IFI prevented by P. RESULTS: We included 22 patients of whom
      86% suffered from AML. P was prescribed in IFI prophylaxies during prolonged and
      severe neutropenia postchemotherapy (72%) or postautologous transplant (28%) and
      initiated 7 days before neutropenia (50% of cases). The mean treatment period was
      18 days. Colonization occurred in one third of patients (43% of Candida
      albicans). Esomeprazole (E) 40 mg was associated in 64% of cases. P prophylaxis
      failed in 50% of cases. Proven/probable IFI occurred in one case. Different
      failure causes were: suspected or possible IFI (n=5) and impossible swallowing
      (n=5). CONCLUSION: P prophylaxis seems to be efficient among these high-risk
      patients. However, a P tardive initiation, an E association, P administration and
      resorption difficulties seem to have a importance in successful treatment. It
      would be interesting to optimize P treatment with plasmatic dosages to ensure
      efficiency and safety for patients.

PMID- 19864089
TI  - Effect of smoking on transient evoked otoacoustic emissions and contralateral
      suppression.
AB  - OBJECTIVE: The present study compared the amplitudes of transient evoked
      otoacoustic emissions (TEOAEs) and efferent suppression in smokers and non
      smokers taking age into consideration. METHODS: Fifty smokers and fifty non
      smokers who had normal hearing sensitivity with age range of 20-69 years were
      considered for the present study. TEOAEs were measured in both the groups of
      subjects across different age groups. The functioning of the efferent auditory
      system was evaluated in both the groups by recording the TEOAEs in the presence
      of a contralateral white noise (CWN) of 70dB SPL. RESULTS: Age did not have a
      significant effect on the TEOAEs amplitude in both the groups of subjects.
      However, the TEOAEs amplitude was significantly reduced in smokers compared to
      non-smokers. The results found a significant effect of age on the amplitude of
      efferent suppression in smokers, however, no significant effect was found in the
      non-smokers group. CONCLUSIONS: It was found that the difference in the amplitude
      of efferent suppression in smokers was significantly greater for each age group
      between 20 and 49 years compared to each age group from 50 to 69 years. Results
      have important implication on the damage to the cochlear structures from smoking.

PMID- 19864090
TI  - Salivary gland choristoma of the middle ear in a child with situs inversus
      totalis.
AB  - Salivary gland choristoma of the middle ear cavity is an extremely rare entity.
      It is thought to be a developmental abnormality and may be associated with
      abnormalities of adjacent structures. We report a case of salivary gland
      choristoma of the middle ear with prominent Korner's septum in a 7-year-old girl
      with situs inversus totalis. Situs inversus totalis is the mirror image reversal
      of the normal position of the internal organs and frequently associated with
      other congenital anomalies. This patient is the first reported case with situs
      inversus totalis, having middle ear salivary gland choristoma and prominent
      bilateral Korner's septae. The management and the differential diagnosis of this
      condition are discussed with the review of the literature.

PMID- 19864091
TI  - Inner ear involvement in Behcet's disease.
AB  - OBJECTIVE: To assess cochlear involvement and hearing loss in patients with
      Behcet's disease (BD). METHOD: Forty-two patients with BD and 24 sex and age
      matched healthy subjects were included in the study. pure-tone audiometry
      including high frequencies (250-16000Hz) and DPOAE were performed to all
      participants. Results of the audiological evaluation were compared and
      correlation between the audiologic status and clinical manifestations of the BD
      were investigated. RESULTS: Bilateral sensorineural hearing loss was detected in
      27 (64.3%) patients. Hearing thresholds were found to be higher in patients with
      BD at all of the frequencies except at 500Hz when compared to control group
      (p<0.05). The difference in the hearing levels tend to increase in high
      frequencies. Compared with control group, distortion products and SNR of the BD
      patients were lower in all of the tested frequencies (p<0.05) which indicates
      weaker outer hair cell motility. There was no correlation between the clinical
      manifestations and the audiological parameters. CONCLUSION: Even having hearing
      levels within normal limits in speech frequencies, increased hearing thresholds
      in high frequencies and decreased signal-noise ratios (SNR) in distortion product
      otoacoustic emission (DPOAE) indicate a cochlear involvement in patients with BD.

PMID- 19864092
TI  - Giant congenital auricular arteriovenous malformation.
AB  - Arteriovenous malformation (AVM) is an uncommon vascular anomaly usually present
      in intracranial location, however may be present in other sites of the body,
      mostly in the head and neck region. The lesion may be present since birth or
      caused by trauma, but may become obvious during puberty or pregnancy. The
      diagnosis can be confirmed by selective angiography. Treatment usually includes
      super selective embolization followed by surgical excision within 48 h. We hereby
      present a rare case of a grotesquely disfiguring congenital auricular
      arteriovenous malformation in a 77-year-old elderly man, which has recently been
      complicated by ulceration, infection and hemorrhage in the past 6 months. The
      pinna showed a 15 cm x 8 cm pulsatile, erythematous, ulcerative hemorrhagic
      swelling which on angiography revealed tortuous superficial temporal and
      occipital arteries supplying the lesion. Complete auricular excision with split
      skin grafting was carried out. The option of preoperative embolization was not
      considered due to his renal dysfunction and the high dye load required for
      embolizing the fast flow arteriovenous malformation.

PMID- 19864093
TI  - Transient evoked otoacoustic emissions in young children with otitis media with
      effusion before and after surgery.
AB  - OBJECTIVE: Otitis media with effusion (OME) is one of the commonest causes of
      acquired hearing loss in children with increasing incidence. In young children
      the diagnosis is restricted to clinical trials and tympanometry whereas
      evaluation of the auditory function is impossible due to noncompliance during
      pure tone audiometry. For this purpose, measurement of otoacoustic emissions,
      especially transient evoked ones (TEOAE), can be applied. The aim of this study
      is to evaluate the parameters of TEOAE in young children with OME prior and after
      surgery. METHODS: Prospective study included 50 children with OME, both sexes,
      aged 2-5 years. Preoperatively tympanometric examination was performed and TEOAE
      were recorded. Surgery was performed under general anesthesia and included
      myringotomy with/without ventilation tube insertion. Measurements of TEOAEs
      (correlation percentage, signal to noise ratio and amplitude) were repeated on
      the first and six day postoperatively as well as 6 weeks and 6 months
      postoperatively. RESULTS: The preoperative TEOAEs were not recorded in 93.5%,
      with values of all TEOAE parameters being the most affected on highest
      frequencies. Significant changes of all TEOAE parameters were found 6 weeks
      postoperatively with further improvement 6 months postoperatively. Statistically
      highly significant difference of TEOAE between examinees with and without
      inserted ventilation tubes was established only in regard to preoperative
      results. CONCLUSION: In small children with OME, application of TEOAEs in follow
      up of surgical effects is a method of choice for hearing screening due to its
      objectivity, simplicity and ease of use even after insertion of ventilation
      tubes. Follow-ups of TEOAE correlation percentage and signal to noise ratio
      reflect the condition earlier than follow-ups of TEOAE amplitude.

PMID- 19864094
TI  - Fluctuating mixed-type hearing loss associated with synovitis-acne-pustulosis
      hyperostosis-osteomyelitis (SAPHO) syndrome.
AB  - Synovitis, acne, palmoplantar pustulosis (PPP), hyperostosis, and osteitis
      (SAPHO) are the characteristic features of SAPHO syndrome. A 53-year-old woman
      had been treated for PPP for 2 years. She complained of hearing loss in the right
      ear, and otitis externa was diagnosed. The pure-tone audiogram (PTA) indicated
      mild hearing loss in the right ear, and her hearing continued to deteriorate
      despite recovery from inflammation. Her tympanogram was of the As-type, and
      acoustic reflex was absent in the right ear. A computed tomography (CT) scan
      revealed bilateral normal ossicles and cochleas. Bone scintigraphy revealed
      tracer uptake in the bilateral sternoclavicular joints, glenohumeral joints, and
      the capital humerus. She was hospitalized for arthralgia, and the pain was
      controlled with steroid therapy. Her right hearing deteriorated soon after the
      tapering of the steroid; her hearing recovered after cyclosporine therapy was
      initiated. The first tonsil provocation test showed increased blood cells in the
      urine, and the second test showed exacerbation of pustulosis. Despite
      immunosuppressant therapy, the arthritis attacks and hearing loss persisted;
      therefore, tonsillectomy was performed, which improved PPP. However, her hearing
      remained unchanged after the operation. We considered that irreversible changes
      might have already developed in the ossicular joints, and ossicular
      reconstruction was performed. Thereafter, her hearing and earache improved.

PMID- 19864095
TI  - Influence of premature rupture of membrane on the cerebral blood flow in low
      birth-weight infant after the delivery.
AB  - Cerebral white matter injury, usually called periventricular leukomalacia (PVL),
      is the most common form of injury to preterm infants that is associated with
      adverse motor and cognitive outcomes. Intrauterine infection may be an important
      etiological factor in PVL, and premature rupture of the membranes (PROM) can be
      identified antepartum. In order to investigate the pathophysiology of cerebral
      white matter injury induced by PROM, the cerebral blood flow (CBF) of the
      internal carotid artery and the vertebral artery was measured by neck
      ultrasonography. The CBF was determined in 84 low-birth-weight infants with
      gestational ages ranging from 24 to 35 weeks, including 71 infants without PROM
      and 13 infants with PROM. The mean blood flow velocity and diameter of each
      vessel were measured on postnatal days 0-70. The intravascular flow volume was
      determined by calculating the mean blood flow velocity and the cross-sectional
      area. The mean blood pressures were recorded, and the ejection fraction was
      determined. The total cerebral blood flow (CBF) was significantly lower in
      infants with PROM than in infants without PROM from day 10 to day 70. The
      ejection fraction was significantly higher in infants with PROM than in infants
      without PROM on days 0, 5, 10, 21, and 42. There was no difference in the mean
      blood pressure between infants with PROM and infants without PROM. The results of
      the present study suggest that PROM may decrease cerebral blood flow after the
      birth.

PMID- 19864096
TI  - The role of EEG in febrile status epilepticus (FSE).
AB  - Febrile status epilepticus is an important neurological emergency and a risk
      factor for later development of epilepsy. There are guidelines recommending
      against the use of EEG in the evaluation of simple febrile seizures but the role
      in febrile status epilepticus is not well established. This article reviews the
      literature on the role of EEG in the evaluation of the patient with prolonged
      febrile seizures, summarizes the findings, and concludes with some simple
      recommendations based upon the existing knowledge. At least 30-40% of EEGs
      obtained within one week of febrile status epilepticus will contain abnormalities
      including focal slowing. In some series focal slowing appears to be associated
      with development of a spike focus in the same location. Prospective series with
      large numbers of patients and follow-up are required to ascertain whether such
      abnormalities are associated with later development of epilepsy.

PMID- 19864097
TI  - [Treatment of a gastric telangiectasia with endoscopic band ligation].

PMID- 19864099
TI  - [Transient global amnesia induced by esophageal functional exploration].

PMID- 19864098
TI  - [Recurrent carcinoid tumor and 18F-DOPA PET].
AB  - We report the case of a carcinoid tumor with suspicion of recurrence on biology.
      Scintigraphic explorations of the whole body had a major role in diagnostic of
      this recurrence. OctreoScan((R)) showed an abdominal uptake corresponding to a
      mesenteric lymph node. PET with (18)F-DOPA also showed a liver uptake
      corresponding to liver metastases.

PMID- 19864100
TI  - Post-colonoscopy massive bleeding from diverticulosis: causality or coincidence?

PMID- 19864101
TI  - Structural enhancement and video endoscopy: results of a large prospective
      comparative study.
AB  - INTRODUCTION: The structural-enhancement (SE) function electronically improves
      the video-endoscopic signal of Olympus processors (EXERA CV-160 or greater),
      enabling an increase in relief that may help in the detection of flat or
      ulcerated and raised lesions, especially those of small size. We assessed the
      diagnostic impact of this technique in the screening of lesions during basic
      video colonoscopy. METHODS: Maximum-level SE was programmed into processors on
      alternate weeks, and endoscopy dates were planned by an assistant unaware of the
      SE schedule, thus ensuring randomization. The endoscopists-senior practitioners
      with 3-29 years of digestive endoscopy practice-were informed of the experiment
      >3 weeks before it began and were not told about it again either before or during
      the study. This was to ensure that endoscopy examinations were performed without
      over-awareness of the technical conditions. GIF-100 to -160 Olympus endoscopes
      were used. RESULTS: During the study, 606 patients underwent upper digestive
      video-endoscopy, 305 with and 301 without the use of the SE function. Of 645
      patients who underwent video colonoscopy, 593 were included in the study and 52
      were excluded due to poor cleansing (8%); of those included, 330 were analyzed
      with and 263 without the SE function. We observed no differences in the detection
      of lesions (small or large) by either upper digestive endoscopy or video
      colonoscopy. CONCLUSION: This is the first study comparing video-endoscopy
      diagnosis with or without SE during upper digestive endoscopy and colonoscopy.
      The SE function available on Olympus video-endoscopy processors had no impact on
      the detection of lesions, not even on those of very small size.

PMID- 19864102
TI  - Perianal presentation of Langerhans cell histiocytosis in children.
AB  - Langerhans cell histiocytosis, previously known as histiocytosis X, is a disease
      whose clinical presentation varies. Although it is uncommon, Langerhans cell
      histiocytosis may involve the perianal region. We report the case of a 2-year-old
      boy who presented with perianal ulcerated vegetative lesions and seborrheic
      dermatitis of the scalp. Biopsy of the lesions showed Langerhans cell
      histiocytosis. This patient did not have any other organ involvement, which is
      rare. The outcome was favourable with vinblastine and corticoids.

PMID- 19864103
TI  - Diffuse primary malignant melanoma of the upper gastrointestinal tract.
AB  - Primary malignant melanomas of the GI tract are very rare. Their symptomatology
      is not specific. We report a 78-year-old Tunisian woman hospitalised with a 6
      month history of recurrent abdominal pain, loss of appetite, weakness and weight
      loss. She had no personal history of cutaneous or ocular melanoma. Upper
      gastrointestinal endoscopy revealed multiple small, raised darkly pigmented
      tumours. Theses lesions were found in the oesophagus, the stomach, the bulb and
      the duodenum. Biopsy specimens were taken and histology showed the presence of
      melanocytic cells with abundant melanin pigment. Immunohistochemically, tumour
      cells were positive for HMB-45. Morphological examinations revealed hepatomegaly
      with multiple nodules with small lymph nodes at the celiac axis. All available
      diagnostic procedures failed to identify any other site of ocular or cutaneous
      melanoma, the present case was considered as primary GI melanoma. Palliative
      chemotherapy was not possible because patient was extremely cachectic and she
      died one month later.

PMID- 19864104
TI  - Liquid chromatograph/tandem mass spectrometry assay for the simultaneous
      determination of chlorogenic acid and cinnamic acid in plasma and its application
      to a pharmacokinetic study.
AB  - A rapid and high sensitive liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) method for simultaneous determination of chlorogenic acid and cinnamic
      acid in human plasma was developed. The analytes and internal standard (IS),
      tinidazole, were extracted from human plasma via liquid/liquid extraction with
      ether-ethyl acetate (1:1, v/v) and separated on an Agilent Zorbax SB C18 column
      within 5min. Quantitation was performed on a triple quadrupole mass spectrometer
      employing electrospray ionization technique, operating in multiple reaction
      monitoring (MRM) and negative ion mode. The precursor to product ion transitions
      monitored for chlorogenic acid, cinnamic acid and IS were m/z 352.9-->191.1,
      146.8-->103.1, 245.6-->126.0, respectively. The assay was validated with linear
      range of 1.00-800.00ng/mL for chlorogenic acid and 0.50-400.00ng/mL for cinnamic
      acid. The intra- and inter-day precisions (RSD%) were within 9.05% for each
      analyte. The absolution recoveries were greater than 74.62% for chlorogenic acid
      and 76.21% for cinnamic acid. Each analyte was proved to be stable during all
      sample storage, preparation and analytic procedures. The method was successfully
      applied to a pharmacokinetic study of Mailuoning injection in 10 healthy
      volunteers.

PMID- 19864105
TI  - Characterization of a novel impurity in bulk drug eprosartan by ESI/MS(n) and
      NMR.
AB  - A simple and sensitive liquid chromatography tandem multi-stage mass spectrometry
      (HPLC/MS(n)) method suitable for eprosartan analysis was developed, by which an
      unknown impurity in bulk drug eprosartan was detected. The fragmentation behavior
      of eprosartan and the impurity in negative mode was investigated. Two molecules
      of CO2 lost from eprosartan precursor ion were observed, while four molecules of
      CO2 were extruded from the deprotonated molecular ion to the MS(3) product ions
      of the impurity. Furthermore, a characteristic fragmentation ion at m/z 335 was
      observed in both eprosartan and the impurity indicated that the impurity might
      have two eprosartan units. The unknown impurity was initially proposed to be
      eprosartan dimer connected via methylene unit at the thiophene moiety on the
      basis of the multi-stage mass spectrometric and exact mass evidences, and it was
      finally elucidated as 4,4'-(5,5'-(1E,1'E)-3,3'-(4,4'-methylenebis(thiophene-4,2
      diyl))bis(2-carboxyprop-1-ene-3,1-diyl)bis(2-butyl-1H-imidazole-5,1
      diyl))bis(methylene) dibenzoic acid by NMR experiments including 1D ((1)H NMR,
      (13)C NMR, DEPT135(0)) and 2D ((1)H-(1)HCOSY, HMQC and HMBC) data.

PMID- 19864106
TI  - Glycine regulates inflammatory markers modifying the energetic balance through
      PPAR and UCP-2.
AB  - Obesity is widely recognized as cause of metabolic syndrome and cardiovascular
      disease. It is provoked by imbalance between the spending and consumption of
      energy associated with a chronic inflammatory condition due to excessive storage
      of fat tissue. Obese patients have an impaired inflammatory profile that
      contributes to the development of vascular complications, with fat tissue being
      partially responsible for controlling both processes: energy balance (through
      PPAR) and inflammatory condition (through inflammatory markers). White adipose
      tissue produces cytokines (IL-6, TNF-alpha, resistin, adiponectin, etc.) and
      participates in a broad spectrum of processes. Recently, glycine has been
      reported to have anti-inflammatory properties which reduce TNF-alpha and IL-6
      levels and increase adiponectin in 3T3-L1 adipocytes and in fat tissue of obese
      mice. In this study, the possible regulatory role of glycine on some factors
      involved in storage and energy burning (PPAR-gamma, PPAR-alpha, PPAR-delta and
      UCP-2) was analyzed in lean and monosodium glutamate-induced obese mice (MSG/Ob
      mice). Glycine clearly increased fat tissue PPAR-gamma expression in lean but not
      in MSG/Ob mice. The PPAR-gamma and PPAR-alpha liver expression was repressed in
      both groups of mice, while the expression of PPAR-delta decreased only in lean
      mice. Interestingly, glycine treatment also suppressed the expression of UCP-2,
      TNF-alpha and IL-6 in lean mice, and increased adiponectin and insulin serum
      levels. In conclusion, glycine regulates the production of inflammatory cytokines
      through PPAR-gamma. These results provide clues on glycine signaling mechanisms
      as an anti-inflammatory agent that might be useful for treatment of metabolic and
      vascular complications associated to inflammation in obesity.

PMID- 19864107
TI  - The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic
      leukemic cell line survival and etoposide resistance.
AB  - B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common
      malignancy in children. The Wnt signaling pathway has been found to be
      extensively involved in cancer onset and progression but its role in BCP-ALL
      remains controversial. We evaluate the role of the Wnt pathway in maintenance of
      BCP-ALL cells and resistance to chemotherapy. Gene expression profile revealed
      that BCP-ALL cells are potentially sensitive to modulation of Wnt pathway. Nalm
      16 and Nalm-6 cell lines displayed low levels of canonical activation, as
      reflected by the virtually complete absence of total beta-catenin in Nalm-6 and
      the beta-catenin cell membrane distribution in Nalm-16 cell line. Canonical
      activation with Wnt3a induced nuclear beta-catenin translocation and led to BCP
      ALL cell death. Lithium chloride (LiCl) also induced a cytotoxic effect on
      leukemic cells. In contrast, both Wnt5a and Dkk-1 increased Nalm-16 cell
      survival. Also, Wnt3a enhanced the in vitro sensitivity of Nalm-16 to etoposide
      (VP-16) while treatment with canonical antagonists protected leukemic cells from
      chemotherapy-induced cell death. Overall, our results suggest that canonical
      activation of the Wnt pathway may exerts a tumor suppressive effect, thus its
      inhibition may support BCP-ALL cell survival.

PMID- 19864108
TI  - "I see what you're saying": intrusive images from listening to a traumatic verbal
      report.
AB  - We tested the hypothesis that intrusive visual images could develop from
      listening to a traumatic verbal report. Eighty-six participants listened to a
      traumatic verbal report under one of three conditions: while shaping plasticine
      (visuospatial condition), while performing articulatory suppression (verbal
      condition), or with no extra task (control condition). Results showed that
      intrusive visual images developed from listening to the traumatic report. In line
      with the idea that central executive processes guide encoding of information,
      intrusion frequency was reduced in both the visuospatial and the verbal condition
      compared to the no task control condition. Overall, this pattern is similar to
      intrusive images from a traumatic film as found in earlier studies. This study
      provides a valuable addition to models of posttraumatic stress disorder and
      autobiographical memory. Additionally, the results have potential implications
      for therapists working with traumatized individuals.

PMID- 19864109
TI  - Parent-child agreement in SCARED and its relationship to anxiety symptoms.
AB  - The aim of this study is to analyze parent-child agreement in the Spanish version
      of the Screen for Anxiety Related Emotional Disorders and its relationship with
      the anxiety symptoms reported in a scheduled interview and the Mini-International
      Neuropsychiatric Interview for Children and Adolescents in order to establish the
      best informant and the degree of incremental validity when both sources of
      information are combined. Results indicated that, as in the original English
      version, parent-children agreement is low, with parents clearly tending to report
      fewer severe symptoms than children. When both parent and child versions were
      related to anxiety symptoms of the scheduled interview, children showed higher
      relationships than parents with all the anxiety categories reported by the
      scheduled interview. Children's scores were also the best predictors of anxiety
      symptoms, while incremental validity of parent's reports was quite low.

PMID- 19864110
TI  - Effects of frequency of feedback on the learning of motor skill in individuals
      with cerebral palsy.
AB  - The purpose of this study was to investigate the effect of frequency of knowledge
      of results (KR) on the learning of dart in individuals with cerebral palsy type
      I. Twenty-four individuals with cerebral palsy (CP) between the ages of 5 and 17
      were chosen for this study. They were put into 3 homogenous groups according to
      their records after 20 throws and practiced for 8 sessions. The first group (0%
      KR) received no KR for any trials, the second group (50% KR) received KR for half
      of their trials (50%), and the third group (100% KR) received KR for all their
      trials (100%). The acquisition test was run immediately after the last session
      and the retention test was run 3 days later. Paired sample t-test and one-way
      ANOVA were used to analyze the data from the acquisition and retention tests.
      According to the results of this study, those with cerebral palsy have the
      ability of acquiring and retaining a new motor skill under the condition of
      feedback provision. Interestingly it was found that too much feedback interferes
      with learning of tasks in individuals with CP as in the average population. This
      finding shows that rules regarding feedback also apply to people afflicted with
      CP.

PMID- 19864111
TI  - Neural network model for completing occluded contours.
AB  - When some parts of a pattern are occluded by other objects, the visual system can
      often estimate the shape of occluded contours from visible parts of the contours.
      This paper proposes a neural network model capable of such function, which is
      called amodal completion. The model is a hierarchical multi-layered network that
      has bottom-up and top-down signal paths. It contains cells of area V1, which
      respond selectively to edges of a particular orientation, and cells of area V2,
      which respond selectively to a particular angle of bend. Using the responses of
      bend-extracting cells, the model predicts the curvature and location of the
      occluded contours. Missing contours are gradually extrapolated and interpolated
      from the visible contours. Computer simulation demonstrates that the model
      performs amodal completion to various stimuli in a similar way as observed by
      psychological experiments.

PMID- 19864112
TI  - Variants of the genes encoding AQP4 and Kir4.1 are associated with subgroups of
      patients with temporal lobe epilepsy.
AB  - OBJECTIVE: The etiopathogenesis of temporal lobe epilepsy (TLE) and its subgroups
      - mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and TLE with
      antecedent febrile seizures (TLE-FS) - is poorly understood. It has been proposed
      that the water channel aquaporin-4 (AQP4) and the potassium channel Kir4.1
      (KCNJ10 gene) act in concert to regulate extracellular K(+) homeostasis and that
      functional alterations of these channels influence neuronal excitability. The
      current study was designed to identify variants of the AQP4 and KCNJ10 genes
      associated with TLE and subgroups of this condition. MATERIAL AND METHODS: We
      included 218 Norwegian patients with TLE and 181 ethnically matched healthy
      controls. An association study was established in which all TLE patients were
      compared with healthy controls. Additionally, subgroups of 56 MTLE-HS patients
      were compared with 162 TLE patients without HS, and 102 TLE-FS patients were
      compared with 105 TLE without FS. RESULTS: We found eight single SNPs, seven in
      KCNJ10 and one between KCNJ10 and KCNJ9, associated with TLE-FS (nominal p-values
      from 0.009 to 0.041). Seven of the SNPs segregate into one large haplotype block
      expanding from KCNJ10 to KCNJ9, including the region interposed those genes. One
      haplotype was overrepresented in the TLE-FS cases (nominal p-value 0.014). These
      results were confirmed by explorative multivariate analysis indicating that a
      combination of SNPs from KCNJ10, the region between KCNJ10 and KCNJ9, and the
      AQP4 gene is associated with TLE-FS. For the TLE cohort as a whole, explorative
      multivariate analysis indicated a combination of SNPs from the KCNJ10 and AQP4
      genes in association with TLE. CONCLUSION: Variations in the AQP4 and the
      KCNJ10/KCNJ9 region are likely to be associated with TLE, particularly TLE-FS,
      supporting the suggestion that perturbations of water and K(+) transport are
      involved in the etiopathogenesis of TLE.

PMID- 19864113
TI  - Impact of real-world ziprasidone dosing on treatment discontinuation rates in
      patients with schizophrenia or bipolar disorder.
AB  - BACKGROUND: The purpose of this study is to evaluate the relationship between
      maximum dose of ziprasidone and time to discontinuation in the treatment of
      schizophrenia/schizoaffective disorder and bipolar disorder in clinical practice.
      METHOD: The 2001-2006 MarketScan Commercial and Medicare Databases were analyzed
      for maximum ziprasidone doses achieved in patients with
      schizophrenia/schizoaffective disorder or bipolar disorder. Ziprasidone maximum
      dose groups were defined as low (20-60 mg/d), medium (61-119 mg/d), or high (120
      160 mg/d). Patients receiving >160 mg/d were excluded. Mean time to
      discontinuation was evaluated across propensity score-matched dosing groups. Cox
      proportional hazard models were used to adjust for confounding when comparing the
      high- and medium-dose groups with the low-dose group. RESULTS: Data were
      available for 33,340 patients with schizophrenia/schizoaffective disorder, of
      whom 16.6% received low dose of ziprasidone, 22.0% medium dose, and 61.4% high
      dose. Of those subjects with bipolar disorder (n=27,751), 26.1% were receiving a
      low dose of ziprasidone, 25.7% a medium dose, and 48.3% a high dose. Among the
      propensity score-matched dosing groups, the respective mean time to
      discontinuation for low, medium, and high doses was 90.5, 117.2, and 201.6d
      within the schizophrenia/schizoaffective disorder cohort and 84.6, 110.7, and
      173.2d within the bipolar cohort (p<0.0001 for all comparisons). The hazard
      ratios for discontinuing therapy were significantly lower for the medium- (0.84,
      0.84) and high-dose (0.57, 0.60) groups relative to the low-dose group in
      schizophrenia/schizoaffective disorder and bipolar disorder, respectively.
      CONCLUSIONS: Patients with schizophrenia/schizoaffective or bipolar disorders
      receiving ziprasidone 120-160 mg/d experienced a statistically significant lower
      discontinuation rate compared with those receiving lower doses.

PMID- 19864114
TI  - Impact of antipsychotic medication on family burden in schizophrenia:
      longitudinal results of CATIE trial.
AB  - BACKGROUND: This study evaluated the effectiveness of first- and second
      generation antipsychotics in reducing family burden associated with
      schizophrenia. METHODS: The family caregivers of 623 SCID-diagnosed patients
      enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE) randomly assigned to a first-generation antipsychotic (perphenazine) or
      one of four second-generation drugs (olanzapine, quetiapine, risperidone or
      ziprasidone) were interviewed about resources provided and stresses experienced
      at baseline and followed for 18 months. Patient symptoms, side effects and
      service use were assessed as well. Hierarchical regression analyses evaluated the
      effect of treatment assignment on four burden factors: problem behavior, resource
      demands and disruption, impairment in activities of daily living and patient
      helpfulness. Intention-to-treat analyses with all available observations
      classified based on initial treatment assignment, including observations after
      medications changed were followed by secondary analyses excluding observations
      after the first medication change, i.e. only considering initial medication.
      RESULTS: Despite significant reductions on the problem behavior and resource
      demands/disruption factors, there were no significant differences between
      perphenazine and any of the second-generation medications. When only initial
      treatment period observations were included, patients were perceived as more
      helpful when medicated with perphenazine as compared to risperidone. In
      comparisons between second-generation drugs, patients on quetiapine were
      perceived as more helpful than those on risperidone (p=0.004). CONCLUSION: In
      this 18-month randomized trial, there was no evidence of superiority of second
      generation antipsychotics in relieving family burden.

PMID- 19864115
TI  - Suicide attempt in first-episode psychosis: a 7.4 year follow-up study.
AB  - BACKGROUND: Individuals with first-episode psychosis demonstrate high rates of
      suicide attempt (SA). AIMS: 1) To examine the prevalence of, and risk factors
      for, SA in a first-episode psychosis (FEP) cohort over a 7.4 year follow-up
      period. 2) To investigate differences between single versus multiple suicide
      attempters. METHODS: This study reports baseline and follow-up data from a
      naturalistic, prospective follow-up of 413 FEP patients treated at a specialist
      early psychosis centre. Assessments were conducted at treatment entry, initial
      symptom remission or stabilization, and long term follow-up. Binary logistic
      regression models were used to assess unadjusted and adjusted associations
      between early illness and sociodemographic characteristics and two outcome
      measures: any SA during follow-up; and multiple SAs. RESULTS: Follow-up data were
      available for 282 participants. Sixty-one (21.6%) made a suicide attempt over the
      follow-up period, including 12 successful suicides. The following baseline risk
      factors increased the risk of any SA: history of self-harm (OR=4.27; p<0.001),
      suicidal tendencies (OR=2.30; p=0.022), being depressed for >50% of the initial
      psychotic episode (OR=2.49; p=0.045), and hopelessness (OR=2.03; p=0.030).
      History of problem alcohol use increased the risk of multiple SAs (OR=4.43; 95%
      CI (1.05-18.7); p=0.043). DISCUSSION: The prevalence of suicide attempt in this
      study exceeds reports from short-term FEP studies but is comparable to longer
      term follow-up studies, indicating that risk remains elevated for at least 7
      years following commencement of treatment. The key predictor of future suicide
      attempt was previous self-harm, indicating that interventions for self-harm are
      required.

PMID- 19864116
TI  - Palmitoylethanolamide modulates pentobarbital-evoked hypnotic effect in mice:
      involvement of allopregnanolone biosynthesis.
AB  - Palmitoylethanolamde (PEA) is an endogenous lipid neuromodulator that mediates a
      broad spectrum of pharmacological effects by activation of peroxisome
      proliferator-activated receptor alpha (PPAR-alpha). Detectable or high levels of
      PEA in the CNS have been found, but the specific function of this lipid remains
      to be clarified. Here we report evidence that PEA, activating PPAR-alpha receptor
      and involving neurosteroids de novo synthesis, modulates pentobarbital-evoked
      hypnotic effect. A single i.c.v. administration of PEA (1-5microg) increases
      pentobarbital induced loss of righting reflex (LORR) duration in mice. This
      effect is mimicked by GW7647 (3microg), a synthetic PPAR-alpha agonist, and
      disappears in PPAR-alpha knockout mice. Antagonism experiments strongly support
      the engaging of neurosteroidogenic pathway in the increase of LORR duration
      induced by PEA. This effect disappeared using two inhibitors blocking the key
      steps of neurosteroids synthesis, aminogluthetimide and finasteride. Moreover, we
      demonstrated that in brainstem PEA increased the expression of steroidogenic
      acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage
      (P450scc), both involved in neurosteroidogenesis. Accordingly, allopregnanolone
      (ALLO) levels were in turn higher in brainstem of PEA and pentobarbital treated
      mice vs pentobarbital alone, as revealed by quantitative analysis using gas
      chromatography-mass spectrometry. A Our results demonstrate that exogenous
      administration of PEA, through a PPAR-alpha-dependent mechanism, modulates
      neurosteroids formation increasing ALLO levels and leading to a positive
      modulation of GABA(A) receptor. These data further strengthen our previous data
      on the role of PPAR-alpha in PEA's actions and could provide a new framework to
      understand its role in the CNS.

PMID- 19864117
TI  - [Usefulness of systematic brain magnetic resonance imaging in children with
      neurofibromatosis type 1].
AB  - BACKGROUND AND AIM: The aim of this study was to evaluate the usefulness of
      systematic screening of asymptomatic neurofibromatosis type 1 (NF1) children with
      magnetic resonance imaging (MRI). PATIENTS AND METHODS: We retrospectively
      reviewed the MRIs of children diagnosed with NF1 disease according to the
      National Institutes of Health criteria, who had been followed for at least 1 year
      by the department of pediatric neurology (Lyon, France). Brain MRI was
      systematically performed in asymptomatic patients under 6 years of age. RESULTS:
      One hundred patients with a median follow-up of 3.7 years (range, 1-8.6 years)
      were reviewed. Brain MRI was performed in a total of 94 children. Nine optic
      pathway gliomas were detected in symptomatic patients. Six children had symptoms
      caused by the tumor. Gliomas remained stable in 10 patients; 1 symptomatic glioma
      in an 8-year-old girl required treatment. Spontaneous regression was seen in 1
      patient. CONCLUSION: Our results suggest that MRI screening of asymptomatic
      children to detect optic pathway gliomas does not improve the therapeutic
      decision and should not be performed systematically. We suggest further
      investigation in collaboration with the French NF Network.

PMID- 19864118
TI  - Adopting model checking techniques for clinical guidelines verification.
AB  - OBJECTIVES: Clinical guidelines (GLs) are assuming a major role in the medical
      area, in order to grant the quality of the medical assistance and to optimize
      medical treatments within healthcare organizations. The verification of
      properties of the GL (e.g., the verification of GL correctness with respect to
      several criteria) is a demanding task, which may be enhanced through the adoption
      of advanced Artificial Intelligence techniques. In this paper, we propose a
      general and flexible approach to address such a task. METHODS AND MATERIALS: Our
      approach to GL verification is based on the integration of a computerized GL
      management system with a model-checker. We propose a general methodology, and we
      instantiate it by loosely coupling GLARE, our system for acquiring, representing
      and executing GLs, with the model-checker SPIN. RESULTS: We have carried out an
      in-depth analysis of the types of properties that can be effectively verified
      using our approach, and we have completed an overview of the usefulness of the
      verification task at the different stages of the GL life-cycle. In particular,
      experimentation on a GL for ischemic stroke has shown that the automatic
      verification of properties in the model checking approach is able to discover
      inconsistencies in the GL that cannot be detected in advance by hand. CONCLUSION:
      Our approach thus represents a further step in the direction of general and
      flexible automated GL verification, which also meets usability requirements.

PMID- 19864119
TI  - Liver resection of colorectal metastases and adjuvant chemotherapy: can published
      data really support clinicians in clinical practice?

PMID- 19864120
TI  - Synchronous ovarian cancer in a patient with pleomorphic lobular breast cancer: a
      therapeutic dilemma.

PMID- 19864121
TI  - Improved n-3 fatty acid status does not modulate insulin resistance in fa/fa
      Zucker rats.
AB  - The objective was to examine the effect of polyunsaturated fatty acid type (plant
      vs fish oil-derived n-3, compared to n-6 fatty acids in the presence of constant
      proportions of saturated, monounsaturated and polyunsaturated fatty acids) on
      obesity, insulin resistance and tissue fatty acid composition in genetically
      obese rats. Six-week-old fa/fa and lean Zucker rats were fed with a 10% (w/w)
      mixed fat diet containing predominantly flax-seed, menhaden or safflower oils for
      9 weeks. There was no effect of dietary lipid on obesity, oral glucose tolerance
      (except t=60min insulin), pancreatic function or molecular markers related to
      insulin, glucose and lipid metabolism, despite increased n-3 fatty acids in
      muscle and adipose tissue. The menhaden oil diet reduced fasting serum free fatty
      acids in both fa/fa and lean rats. These data suggest that n-3 composition does
      not alter obesity and insulin resistance in the fa/fa Zucker rat model when
      dietary lipid classes are balanced.

PMID- 19864122
TI  - Test-retest stability of the oral niacin test and electrodermal activity in
      patients with schizophrenia.
AB  - In schizophrenia, well-replicated findings support an attenuated niacin skin
      flush response. We have previously reported a delayed skin-flush after niacin
      ingestion and also an association between niacin non-responding and electrodermal
      non-responding in schizophrenia. The stability of the niacin and electrodermal
      tests was now studied in a test-retest design. An additional aim was to assess
      the association previously found. Twenty-three patients with schizophrenia
      underwent two sessions 3 months apart during which an oral niacin test was
      conducted and electrodermal activity was measured. Despite similar values for
      niacin outcome variables at the group level, there was high intraindividual
      variation. Test-retest stability for the oral niacin test was thus low, although
      a trend toward correlation for the dichotomous response criterion was found. Most
      electrodermal measures correlated between baseline and retest. A significant
      association between the tests was again found; niacin non-responding implied
      electrodermal non-responding, providing further support for a common underlying
      aberration in schizophrenia.

PMID- 19864124
TI  - Investigation of health care waste management in Binzhou District, China.
AB  - In China, national regulations and standards for health care waste management
      were implemented in 2003. To investigate the current status of health care waste
      management at different levels of health care facilities (HCF) after the
      implementation of these regulations, one tertiary hospital, one secondary
      hospital, and four primary health care centers from Binzhou District were visited
      and 145 medical staff members and 24 cleaning personnel were interviewed.
      Generated medical waste totaled 1.22, 0.77, and 1.17 kg/bed/day in tertiary,
      secondary, and primary HCF, respectively. The amount of medical waste generated
      in primary health care centers was much higher than that in secondary hospitals,
      which may be attributed to general waste being mixed with medical waste. This
      study found that the level of the HCF, responsibility for medical waste
      management in departments and wards, educational background and training
      experience can be factors that determine medical staff members' knowledge of
      health care waste management policy. Regular training programs and sufficient
      provision of protective measures are urgently needed to improve occupational
      safety for cleaning personnel. Financing and administrative monitoring by local
      authorities is needed to improve handling practices and the implementation of off
      site centralized disposal in primary health care centers.

PMID- 19864123
TI  - Carrageenan-induced innate immune response is modified by enzymes that hydrolyze
      distinct galactosidic bonds.
AB  - The common food additive carrageenan (CGN) predictably induces intestinal
      inflammation in animal models. Mechanisms of CGN-induced nuclear factor kappaB
      and interleukin-8 (IL-8) stimulation include an immune-mediated pathway involving
      toll-like receptor 4 (TLR4) and B-cell lymphoma/leukemia 10 (BCL10) and a
      reactive oxygen species (ROS)-mediated pathway. To determine how the structure of
      CGN contributes to its initiation of inflammation through these two distinct
      mechanisms, we treated CGNs with galactosidases and carrageenases (CGNases) and
      determined the impact on IL-8 secretion and BCL10 production. Hydrolysis of CGN
      by the enzyme alpha-1->(3,6)-galactosidase significantly reduced increases in IL
      8 and BCL10, but other galactosidases tested, including alpha-1->6-galactosidase,
      beta-1->4-galactosidase and beta-1->3,6-galactosidase, had no effect. In
      contrast, specific kappa-CGNases or iota-CGNases, which hydrolyze beta-1,4
      galactosidic bonds, produced increases in IL-8 and BCL10 attributable to
      increased exposure of the immunogenic alpha-1->3-galactosidic epitope of CGN to
      TLR4. These results were consistent with induction of innate immune response by
      an interaction of TLR4 with the unusual alpha-d-Gal-(1->3)-d-Gal epitope present
      in CGN. Activation of the ROS-mediated pathway was unaffected by treatment of
      kappa-CGN with either kappa-CGNase (3 mg/L), alpha-1->(3,6)-galactosidase (20
      mU/ml) or these enzymes in combination, indicating that changes in IL-8
      production were attributable to the effects of induction of inflammation on the
      TLR4-BCL10-mediated innate immune pathway. These findings provide new information
      about the specificity of carbohydrate-protein interaction between CGN and TLR4
      and may help to devise treatments that modify the immune reactivity induced by
      carbohydrate antigens.

PMID- 19864125
TI  - Comparison of DNA, aminoethylglycyl PNA and pyrrolidinyl PNA as probes for
      detection of DNA hybridization using surface plasmon resonance technique.
AB  - Pyrrolidinyl peptide nucleic acid bearing a D-prolyl-2
      aminocyclopentanecarboxylic acid backbone (acpcPNA) has been evaluated as a new
      sensing probe for detection of DNA hybridization. In this study, the biotinylated
      acpcPNA was immobilized on surface plasmon resonance (SPR) sensor chips via
      biotin-streptavidin interactions for solid-phase DNA hybridization. A critical
      comparison between acpcPNA, DNA and conventional peptide nucleic acid (aegPNA)
      probes of the same sequence was made by means of SPR on various important
      aspects. These include the effect of ionic strength on hybridization efficiency,
      the specificity to detect the mismatch(es) in target DNAs, the direction of
      binding (parallel or antiparallel) to target DNAs, and the effect of target DNA
      concentration on hybridization efficiency. Results indicated that the immobilized
      acpcPNA probe possesses distinct hybridization properties relative to aegPNA
      (and/or DNA) counterparts, including a higher single-base mismatch sensitivity,
      antiparallel selectivity and low ionic strength dependence of target
      hybridization. These properties substantiate the acpcPNA applicability as sensor
      probes for clinical and diagnostic applications. With a proper selection of
      regeneration conditions (10 mM NaOH, 2 min exposure), the sensor can be reused
      for multiple cycles of hybridization with as little as 1.3% loss in hybridization
      activity per regeneration cycle.

PMID- 19864126
TI  - Vascular morphogenesis: a Wnt for every vessel?
AB  - Blood vessel development requires orchestrated activities of heterogeneous
      endothelial cell (EC) populations to create a hierarchically branched tubular
      network. Endothelial heterogeneity is manifested in organ-specific endothelial
      differentiation and function in the mature vasculature. During sprouting
      angiogenesis, ECs are specified by Dll4/Notch signalling into leading tip cells
      and following stalk cells, which together through coordinated migration and
      proliferation shape the nascent vascular sprout. Wnt-signalling influences many
      aspects of branching tubulogenesis in various species and organ systems, often in
      coordination with Notch signalling. Recent advances in vascular biology highlight
      important roles for multiple components of the Wnt-signalling pathway in
      regulating cell differentiation, proliferation, survival, cell junctions and
      polarity. Here, we review the emerging concepts of the molecular actions of Wnt
      signalling in regulating differential behaviour and/or cell functions during
      vascular development.

PMID- 19864127
TI  - Effects of plant diversity on nutrient retention and enzyme activities in a full
      scale constructed wetland.
AB  - This study focused on the relationship between plant diversity (six species
      richness levels) and nutrient retention and enzyme activities associated with
      carbon, nitrogen and phosphorus cycling in a full-scale constructed wetland (CW)
      fed with post-treatment domestic wastewater. Effects of plant species richness on
      nutrient retention and enzyme activities were assessed using soil chemical and
      zymological methods, respectively. Retention of NH(4)-N and NO(3)-N in the
      wetland substrate increased with increasing species richness, while phosphorus
      retention significantly decreased under the richness level of 16 species per
      plot. Activities of enzymes such as dehydrogenase, beta-glucosidase, invertase,
      phenol oxidase, L-arsparaginase, protease and nitrate reductase, while they were
      affected by plant species richness, were strongly depended on the presence or
      absence of plants in CW substrate, while activities of enzymes such as CM
      cellulase, urease and acid phosphatase were strongly depended on plant species
      richness. We conclude that plant species richness influenced nutrient retention
      and enzyme activities in the substrate in our subtropical CW; increase plant
      species richness in CW will likely improve the efficiency of wastewater
      treatment.

PMID- 19864128
TI  - Effect of mixed liquor pH on the removal of trace organic contaminants in a
      membrane bioreactor.
AB  - Experiments were conducted over approximately 7 months to investigate the effects
      of mixed liquor pH (between pH 5 and 9) on the removal of trace organics by a
      submerged MBR system. Removal efficiencies of ionisable trace organics
      (sulfamethoxazole, ibuprofen, ketoprofen, and diclofenac) were strongly pH
      dependent. However, the underlying removal mechanisms are different for ionisable
      and non-ionisable compounds. High removal efficiencies of these ionisable trace
      organics at pH 5 could possibly be attributed to their speciation behaviour. At
      this pH, these compounds exist predominantly in their hydrophobic form.
      Consequently, they could readily adsorb to the activated sludge, resulting in
      higher removal efficiency in comparison to under less acidic conditions in the
      reactor. Removal efficiencies of the two non-ionisable compounds bisphenol A and
      carbamazepine were relatively independent of the mixed liquor pH. Results
      reported here suggest an apparent connection between physicochemical properties
      of the compounds and their removal efficiencies by MBRs.

PMID- 19864129
TI  - Synthesis of 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one
      derivatives and their cytotoxic activities.
AB  - A series of novel 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20
      one derivatives were synthesized and characterized by NMR, HRMS. The pregnenolone
      (1) was first biotransformed by Mucor circinelloides var lusitanicus to 3beta,
      7alpha, 11alpha-trihydroxy-pregn-5-en-20-one (3), then 3 was treated with various
      benzaldehydes to produce 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5
      en-20-one derivatives. These derivatives showed remarkable activity against EC109
      cells. The absolute configuration of 3 was also confirmed by signal-crystal X-ray
      analysis.

PMID- 19864131
TI  - Aptamers as a model for functional evaluation of LNA and 2'-amino LNA.
AB  - The affinity change upon incorporation of LNA and 2'-amino-LNA monomers into an
      avidin binding DNA aptamer is described. The kinetic profile of selected modified
      aptamer was obtained by surface plasmon resonance experiments and compared with
      the profile of the parent unmodified DNA aptamer. We report significant
      improvement of avidin binding affinity by the incorporation of single LNA
      modifications into the aptamer, and successful incorporation of 2'-amino LNA as a
      novel monomer in aptamers with potential function as carrier unit for additional
      molecular entities.

PMID- 19864130
TI  - Design and synthesis of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors.
AB  - Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays
      a significant role in neuronal development. In association with p25, CDK5
      abnormally phosphorylates a number of cellular targets involved in
      neurodegenerative disorders. Using active site homology and previous structure
      activity relationships, a new series of potent CDK5 inhibitors was designed. This
      report describes the optimization of 6-oxo-1,6-dihydropyridines as CDK5
      inhibitors.

PMID- 19864132
TI  - 5-Aryl indanones and derivatives as non-steroidal progesterone receptor
      modulators.
AB  - Novel 5-aryl indanones, inden-1-one oximes, and inden-1-ols were synthesized and
      evaluated as progesterone receptor (PR) modulators using the T47D cell alkaline
      phosphatase assay. Both PR agonists and antagonists were achieved with
      appropriate 3- and 5-substitution from indanones and inden-1-ols while inden-1
      one oximes provided only PR antagonists. Several compounds such as 10 and 11
      demonstrated potent in vitro PR agonist potency similar to that of steroidal
      progesterone (1). In addition, a number of compounds (e.g., 12, 13, 17, 18)
      showed potent PR antagonist activity indicating the indanones and derivatives are
      promising PR modulator templates.

PMID- 19864133
TI  - 2-Amino-5-aryl-pyridines as selective CB2 agonists: synthesis and investigation
      of structure-activity relationships.
AB  - 2-Amino-5-aryl-pyridines, exemplified by compound 1, had been identified as a
      synthetically tractable series of CB(2) agonists from a high-throughput screen of
      the GlaxoSmithKline compound collection. Described herein are the results of an
      investigation of the structure-activity relationships (SAR) which led to the
      identification a number of potent and selective agonists.

PMID- 19864134
TI  - A method for terminus proteomics: selective isolation and labeling of N-terminal
      peptide from protein through transamination reaction.
AB  - A novel method for selectively labeling and isolating N-terminal peptide from
      protein has been developed. An N(alpha)-amino group of protein was converted to a
      carbonyl group through transamination reaction and the resulting carbonyl group
      was modified with O-(4-nitrobenzyl)hydroxylamine (NBHA). After proteolytic
      digestion using Grifola frondosa metalloendopeptidase (LysN), the modified N
      terminal peptide remained unbound in the following treatment using amino-reactive
      p-phenylenediisothiocyanate (DITC) glass, whereas peptides other than the N
      terminal peptide were effectively scavenged from the supernatant solution. The
      modified N-terminal peptide was thus successfully isolated and sequenced by
      matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI
      MS/MS) analysis.

PMID- 19864135
TI  - Discovery and SAR of cyclic isothioureas as novel NPY Y1 receptor antagonists.
AB  - A class of novel 2-aminobenzothiazoles have been identified as NPY Y(1)
      antagonists. Various N-heterocyclic substituted aminophenethyl-2
      aminobenzothiazole analogs were synthesized to explore the SAR. Isothiourea
      analogs and ligands with high potency (K(i) 30 nM) have been identified.

PMID- 19864136
TI  - Non-hinge-binding pyrazolo[1,5-a]pyrimidines as potent B-Raf kinase inhibitors.
AB  - As part of our research effort to discover B-Raf kinase inhibitors, we prepared a
      series of C-3 substituted N-(3-(pyrazolo[1,5-a]pyrimidin-7-yl)phenyl)-3
      (trifluoromethyl)benzamides. X-ray crystallography studies revealed that one of
      the more potent inhibitors (10n) bound to B-Raf kinase without forming a hinge
      binding hydrogen bond. With basic amine residues appended to C-3 aryl residues,
      cellular activity and solubility were enhanced over previously described
      compounds of this class.

PMID- 19864137
TI  - Implementation of a research awareness program in the critical care unit: effects
      on families and clinicians.
AB  - BACKGROUND: Successful conduct of research studies in the critically ill requires
      communication with families, substitute decision-makers and clinicians.
      OBJECTIVE: To assess the effect of a communication package on attitude, knowledge
      and research awareness among family members and clinicians. METHODS: We conducted
      a prospective, single centre, before and after study. We distributed a validated
      questionnaire to family members and clinicians assessing the three domains of
      research attitude, knowledge and awareness before and after implementation of a
      research communication package consisting of an informational pamphlet and
      display poster. RESULTS: Response rates for the family member survey were 22%
      (baseline) and 15% (post-intervention). No differences were found in the
      attitude, knowledge and awareness of family members following implementation of
      the research communication package. The global awareness score (calculated by
      summing the domain responses) rose 4.0 points (P=0.056). Response rates for
      clinicians were 36% (baseline) and 33% (post-intervention). No differences were
      found in attitude, knowledge and awareness and global awareness score.
      CONCLUSION: Passive dissemination of research materials was not sufficient to
      generate an increased awareness, knowledge, or perceived utility of research.

PMID- 19864138
TI  - Evaluation of force plate-less estimation of the trajectory of the centre of
      pressure during gait. Comparison of two anthropometric models.
AB  - The estimation of the trajectory of the centre of pressure during gait is
      possible without using force plate by modelling the whole body as a multi-segment
      chain. The kinematics and inertial parameters of each segment are necessary to
      determine the ground reaction forces and moments. The position of the centre of
      pressure can then be calculated at each frame of time. The objective of the study
      was to evaluate the accuracy of the estimation of the position of the centre of
      pressure during gait obtained without force plate data. Segment inertial
      parameters were determined using a proportional model and a geometric model. The
      modelling and calculations were computed for six volunteers and the estimated
      centres of pressure were compared to the centre of pressure measured using force
      plates considered as the gold standard. The estimation was better using the
      geometric model with an accuracy of 33 mm (4.1% of the peak-to-peak amplitude) on
      the longitudinal axis and 14.2 mm (12.9% of the peak-to-peak amplitude) on the
      lateral axis.

PMID- 19864139
TI  - Multiple spinal dural arteriovenous fistulae and deterioration post lumbar
      puncture.
AB  - We report a 73-year-old man presenting with bilateral leg numbness and weakness.
      Three spinal dural arteriovenous fistulae (SDAVF) were found after clinical
      deterioration post lumbar puncture (LP). This patient highlights the difficulties
      in the diagnosis and management of SDAVF, and the risks of LP.

PMID- 19864140
TI  - Electrocorticogram changes during corpus callosotomy for uncontrolled symptomatic
      generalized epilepsy.
AB  - We report a 19-year-old man who presented to our facility with medically
      intractable, symptomatic generalized epilepsy manifesting as generalized tonic
      clonic seizures (GTCs). Before he underwent an anterior callosotomy (6 cm), these
      seizures, which he had experienced for 11 years, seemed to have a left-sided
      focal origin. Intraoperatively, no epileptiform discharges were found on the
      electrocorticogram (ECoG) performed prior to sectioning, but more than 10 left
      sided seizures were recorded after sectioning. In the 10 years since surgery, the
      patient's seizures have remained generalized; however, the frequency and severity
      of the seizures have decreased. These findings indicate that the presence of
      electrocorticographic seizures, as measured by ECoG immediately following
      callosotomy, may not predict a poor surgical outcome, even though such a finding
      might be indicative of epileptogenicity in general.

PMID- 19864141
TI  - Surgical treatment for musicogenic epilepsy.
AB  - We report a patient with medically intractable musicogenic epilepsy (ME) who was
      treated with surgery. Using the non-invasive methods of ictal and interictal
      electroencephalography (EEG), MRI, interictal single photon emission computed
      tomography and clinical manifestations, we first localized the musicogenic
      seizures (MS). The ictal onset zone was then further localized using intracranial
      EEG to the middle part of the left superior temporal gyrus. Surgical resection of
      the epileptogenic zone was then performed. The patient had two seizures within 2
      weeks post-operatively, but has then had no seizures during the following year
      (Engel class II). The results suggest that patients who have medically
      intractable ME combined with unilateral ictal onset zones should be considered
      for the surgical treatment of epilepsy.

PMID- 19864142
TI  - Spinal drop metastasis from grade I skull base chondrosarcoma.
AB  - Chondrosarcoma of the skull base is a rare tumour with a good prognosis following
      surgical resection. We describe a patient with low-grade chondrosarcoma of the
      skull base with intradural extramedullary spinal metastases. A 31-year-old female
      with grade 1 chondrosarcoma involving the cavernous sinus, sphenoid wing and
      clivus presented at age 19. The tumour was subtotally excised at initial surgery
      and over the following 4 years, 3 subsequent resections were undertaken for
      tumour progression followed by proton beam radiotherapy to the residual tumour.
      The patient re-presented with cervical radiculopathy 7 years later. MRI showed
      multiple, intradural extramedullary spinal drop metastases. Following surgical
      excision of the symptomatic lesion, histological diagnosis was confirmed as a
      mixed hyaline/myxoid grade 1 chondrosarcoma. Patients with skull base
      chondrosarcoma with intradural extension should have whole spine imaging as part
      of long-term monitoring to exclude drop metastases, particularly after intradural
      surgery.

PMID- 19864143
TI  - MRI and pathological findings of rheumatoid meningitis.
AB  - Rheumatoid meningitis (RM) is one of the most severe complications of rheumatoid
      arthritis. The mortality rate of RM is relatively high and diagnosis can be
      difficult. We present an 80-year-old woman who was diagnosed with microscopic
      findings of RM after analysis of biopsy specimens taken from a brain lesion. MRI
      scanning revealed meningeal enhancement in the brain, and the pathological
      findings were those of meningeal lymphocytic infiltration, vasculitis and
      rheumatoid nodules. RM is a treatable disease and in this patient RM was
      diagnosed on the basis of biopsy findings.

PMID- 19864144
TI  - Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown.
AB  - It is becoming increasingly apparent that spatial regulation of cell signalling
      processes is critical to normal cellular function. In this regard, cAMP
      signalling regulates many pivotal cellular processes and has provided the
      paradigm for signal compartmentalization. Recent advances show that isoforms of
      the cAMP-degrading phosphodiesterase-4 (PDE4) family are targeted to discrete
      signalling complexes. There they sculpt local cAMP gradients that can be detected
      by genetically encoded cAMP sensors, and gate the activation of spatially
      localized signalling through sequestered PKA and EPAC sub-populations. Genes for
      these important regulatory enzymes are linked to schizophrenia, stroke and
      asthma, thus indicating the therapeutic potential that selective inhibitors could
      have as anti-inflammatory, anti-depressant and cognitive enhancer agents.

PMID- 19864145
TI  - Physical examination and in vivo kinematics in two posterior cruciate ligament
      retaining total knee arthroplasty designs.
AB  - The aim of this study was to investigate anteroposterior instability in the CKS
      and the PFC total knee arthroplasty (TKA) designs. Physical examinations,
      including VAS, IKS and WOMAC were performed in combination with a detailed
      fluoroscopic measurement technique for three-dimensional kinematic assessment of
      TKA design function. Anteroposterior instability rated with the IKS was not
      significantly different (p=0.34), but patients with a CKS design showed more
      limitations according to the WOMAC joint stiffness total score, and for items
      regarding higher flexion activities in the WOMAC score for knee disability.
      Kinematic analyses showed that the CKS design tended to have more anterior
      sliding of the femur on the tibia during mid- and deep flexion activities. The
      sliding distance was larger at the medial than at the lateral side. This
      phenomenon has also been described for posterior cruciate ligament deficient
      knees. Furthermore, the CKS design showed a significantly lower range of tibial
      rotation (p<0.05) from maximum extension to maximum flexion during deep knee bend
      activities. Kinematic differences can be ascribed to posterior cruciate ligament
      deficiency/laxity or differences in TKA designs.

PMID- 19864146
TI  - Increasing pre-activation of the quadriceps muscle protects the anterior cruciate
      ligament during the landing phase of a jump: an in vitro simulation.
AB  - We hypothesize that application of an unopposed quadriceps force coupled with an
      impulsive ground reaction force may induce anterior cruciate ligament (ACL)
      injury. This situation is similar to landing from a jump if only the quadriceps
      muscle is active; an unlikely but presumably dangerous circumstance. The purpose
      of this study was to test our hypothesis using in vitro simulation of jump
      landing. A jump-landing simulator was utilized. Nine cadaveric knees were tested
      at an initial flexion angle of 20 degrees . Each ACL was instrumented with a
      differential variable reluctance transducer (DVRT). Quadriceps pre-activation
      forces (QPFs) ranging from 25N to 700N were applied to each knee, followed by an
      impulsive ground reaction force produced by a carriage-mounted drop weight (7kg)
      that impulsively drove the ankle upward. ACL strain was monitored before landing
      due to application of QPF (pre-activation strain) and at landing due to
      application of the ground reaction force (landing strain). No ACLs were injured.
      Pre-activation strains exhibited a positive correlation with QPF (r=0.674,
      p<0.001) while landing strains showed a negative correlation (r=-0.235, p=0.032).
      Total ACL strain (pre-activation+landing strain) showed no correlation with QPF
      (r=0.023, p=0.428). Our findings indicate that elevated QPF increases pre
      activation strain but reduces the landing strain and is therefore protective post
      landing. Overall, there is a complete lack of correlation between "total" ACL
      strain and QPF suggesting that the total strain in the ACL is independent of the
      QPF under the simulated conditions.

PMID- 19864147
TI  - Antimalarial activities of ferroquine conjugates with either glutathione
      reductase inhibitors or glutathione depletors via a hydrolyzable amide linker.
AB  - Based on the prodrug concept as well as the combination of two different classes
      of antimalarial agents, we designed and synthesized two series of ferrocenic
      antimalarial dual molecules consisting of a ferroquine analogue conjugated with a
      glutathione reductase inhibitor (or a glutathione depletor) through a cleavable
      amide bond in order to target two essential pathways in the malarial parasites.
      The results showed no enhancement of the antimalarial activity of the dual
      molecules but evidenced a unique mode of action of ferroquine and ferrocenyl
      analogues distinct of those of chloroquine and nonferrocenic 4-aminoquinoline
      analogues.

PMID- 19864148
TI  - Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N
      terminal pyroglutamate capping group.
AB  - The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant
      protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites
      across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK)
      analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal
      homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had
      similar bioactivity and biophysical properties to the parent peptide, and an
      improved resistance to peptidase-mediated degradation was observed compared with
      the non-end-capped peptide obtained using standard recombinant technology.

PMID- 19864149
TI  - Synthesis, tautomerism, and antimicrobial, anti-HCV, anti-SSPE, antioxidant, and
      antitumor activities of arylazobenzosuberones.
AB  - 2-Dimethylaminomethylene-1-benzosuberone 1 was coupled with diazotized aniline
      derivatives to afford a series of the hitherto unreported 2-arylazo-1
      benzosuberones 3a-i. The tautomeric structure and the effect of substituents on
      the tautomeric form (s) of the products 3a-i were discussed. Similar coupling of
      the enaminone 1 with diazonium salts of heterocyclic amines gave the respective
      fused azolotriazino-benzosuberones. Some of the newly synthesized compounds
      showed potent antimicrobial, anti-HCV, antioxidant, antitumor (as topoisomerase I
      inhibitors), and antimicrobial activities.

PMID- 19864150
TI  - X-ray phase contrast imaging of the bone-cartilage interface.
AB  - Synovial joints articulate in a lubricating environment, the system providing for
      smooth articulation. The articular cartilage overlying the bone consists of a
      network of collagen fibres. This network is essential to cartilage integrity,
      suffering damage in degenerative joint disease such as osteoarthritis. At Surrey
      and also in work conducted by this group at the Paul Scherrer Institute (PSI)
      synchrotron site we have been applying a number of techniques to study the bone
      cartilage interface and of changes occurring in this with disease. One of the
      techniques attracting particular interest is X-ray phase contrast imaging,
      yielding information on anatomical features that manifest from the large scale
      organisation of collagen and the mineralised phase contained within the collagen
      fibres in the deep cartilage zone. This work briefly reviews some of the basic
      supporting physics of X-ray phase contrast imaging and then shows example images
      of the articular surface and subchondral bone and other supporting results
      obtained to-date. Present results have been obtained on sections of bone not
      displaying evidence of an osteoarthritic lesion and can be used as a baseline
      against which diseased bone can be compared.

PMID- 19864151
TI  - Natural radioactivity in underground water from the Outer Carpathians in Poland
      with the use of nuclear spectrometry techniques.
AB  - The investigations of natural radioactivity in underground mineral water and
      spring water in health resorts in the Outer Carpathians were performed. Samples
      from 40 water springs were collected 3-4 times over a period of 10 years (1997
      2007). In order to obtain necessary data, two different nuclear spectrometry
      techniques were applied: WinSpectral alphabeta 1414 liquid scintillation counter
      from Wallac and alpha-spectrometer 7401 VR from Canberra-Packard, USA with the
      silicon surface barrier detector. The activity concentrations of (222)Rn in the
      investigated samples varied from below 1 to 50 Bq/l. For radium isotopes the
      concentrations were in a range from below 10 to 490 mBq/l for (226)Ra and from 29
      to 397 mBq/l for (228)Ra. The highest concentrations for both radium isotopes
      were obtained for medicinal water Zuber III from Krynica spa. The activity
      concentrations for uranium isotopes varied from below 0.5 to 16 mBq/l for (238)U
      and from below 0.5 to 162 mBq/l for (234)U with the highest values obtained for
      water Zuber IV. The highest annual effective dose arising from mainly radium
      isotopes was obtained for Zuber III water and was equal to 75 microSv/yr.
      Additionally, the annual effective doses due to (222)Rn consumed with water were
      also estimated. The isotopic ratios between isotopes originating from the same
      decay chain ((234)U/(238)U, (226)Ra/(238)U) and from different radioactive decay
      chains ((226)Ra/(228)Ra) were determined. The correlations between different
      isotopes were presented.

PMID- 19864153
TI  - An unusual dysphagia.

PMID- 19864154
TI  - The management of thoracic inlet syndrome associated with Hurler's syndrome: a
      novel surgical technique.
AB  - A 21-year-old male developed significant swelling of his tongue after a
      respiratory arrest. The patient had a history of Hurler's syndrome. Magnetic
      resonance imaging (MRI) angiogram delineated that the swelling was due to
      compression of his internal jugular veins at the level of the first rib,
      resulting in thoracic inlet obstruction. The standard surgical treatment of
      thoracic inlet obstruction was not suitable in this patient's case due to his
      short thick neck and his characteristic Hurler's syndrome body habitus.
      Therefore, a novel surgical strategy was used to decompress his head and neck
      vessels. The manubrium was widened using an iliac crest bone graft, stabilised
      using internal fixation plates and reconstructed with a pectoral muscle flap.

PMID- 19864155
TI  - Thrombus formation due to flow competition after apico-aortic conduit.
AB  - We report a case of unusual thrombus formation and describe the risk of
      perioperative myocardial infarction or stroke in severe aortic stenosis after
      apico-aortic conduit. An 86-year-old woman was admitted with aggravation of
      dyspnoea on exertion and chest pain. She was complicated with severe aortic
      stenosis and liver cirrhosis. Echocardiography demonstrated a peak pressure
      gradient of 50 mmHg across the aortic valve with ejection fraction of 51%. Since
      she had porcelain aorta and severe liver dysfunction, we selected an apico-aortic
      conduit under left ventricular fibrillation as treatment. Postoperative computed
      tomography showed a large thrombus in the descending aorta. Using strict
      anticoagulation therapy, the thrombus almost disappeared and thrombo-embolic
      events did not occur after surgery.

PMID- 19864157
TI  - The role of energy transfer in bioluminescence quenching by xanthene dyes.
AB  - The paper reports the experimental results of bioluminescence quenching in the
      coupled enzyme system NADH:FMN-oxidoreductase-luciferase in the presence of
      xanthene dyes (fluorescein, eosin Y, erythrosin B) featured by the rate constants
      of intersystem crossing. From the spectral data and with the help of kinetic
      model the rate constants of energy transfer from emitter to dye were determined
      (2.9 x 10(12)-6.5 x 10(13) M(-1) s(-1)) and the emitter lifetime was estimated
      (1.2-2.7 ns). The calculated rate constants of energy transfer in a series of
      xanthene molecules are higher than the diffusion-controlled constants. The rate
      constants of energy transfer correlate with the probability of intersystem
      crossing of a dye. The combined analysis of emitter fluorescence quenching and
      acceptor fluorescence enhancement indicates that the significant bioluminescence
      intensity decrease in the presence of xanthene dyes is determined by both the
      quenching processes via the energy transfer and the inhibition of bioluminescent
      reaction.

PMID- 19864158
TI  - Epigenetic mechanisms in the development of type 2 diabetes.
AB  - Type 2 diabetes (T2D) is a disorder of complex genetics influenced by
      interactions between susceptible genetic loci and environmental perturbations.
      Intrauterine growth retardation is one such environmental perturbation linked to
      the development of T2D in adulthood. An abnormal metabolic intrauterine milieu
      affects fetal development by permanently modifying expression of key genes
      regulating beta-cell development (Pdx1) and glucose transport (Glut4) in muscle.
      Epigenetic regulation of gene expression is one mechanism by which genetic
      susceptibility and environmental insults can lead to T2D. Therefore, therapeutic
      agents targeting epigenetic gene regulation can ultimately be used to treat T2D;
      however, there is much to be learned about genome-wide epigenetic programming of
      health and disease before these therapies can be used in patient care.

PMID- 19864160
TI  - High-risk retrieval of adherent and chronically implanted IVC filters: techniques
      for removal and management of thrombotic complications.
AB  - PURPOSE: To evaluate the safety and efficacy of aggressive techniques for
      retrieving adherent and chronically implanted inferior vena cava (IVC) filters.
      MATERIALS AND METHODS: A single-center retrospective review was performed on all
      patients who underwent attempted filter retrieval from October 2007 through
      October 2008. Patients were included in the study if they had an adherent filter,
      refractory to standard retrieval techniques, and underwent high-risk retrieval
      after procedural risks were deemed lower than risks of long-term filter
      implantation. RESULTS: Fourteen patients were diagnosed with an adherent filter,
      13 (93%) of whom were candidates for high-risk retrieval. These patients included
      seven men and six women (mean age, 40 years; age range, 18-71 years). Nine of the
      13 patients (69%) were referred from an outside hospital. Filter retrieval was
      performed for the following indications: to avoid the risk of long-term
      thrombotic complications in a young patient (n= 6), to treat symptomatic filter
      related IVC stenosis (n= 5), to treat symptomatic filter penetration (n= 1), and
      to avoid the need for lifelong anticoagulation (n= 1). There were eight Gunther
      Tulip filters (mean dwell time, 356 days; range 53-1,181 days), two Optease
      filters (mean dwell time, 62 days; range, 52-72 days), one G2 filter (dwell time,
      420 days), and two Recovery filters (mean dwell time, 1,630 days; range, 1,429
      1,830 days). Three IVC occlusions necessitated recanalization to facilitate
      retrieval. High-risk retrieval with use of various techniques with aggressive
      force was successful in all 13 patients (100%). Partial caval thrombosis occurred
      in the first four patients (31%) but did not occur after procedural modifications
      were implemented. There were no complications at clinical follow-up (mean, 221
      days; range, 84-452 days). CONCLUSIONS: Alternative techniques can be used to
      retrieve adherent IVC filters implanted for up to 3-5 years. Although caval
      thrombosis was an observed complication, protocol modifications appeared to
      reduce this risk.

PMID- 19864159
TI  - Torpor induction in mammals: recent discoveries fueling new ideas.
AB  - When faced with a harsh climate or inadequate food, some mammals enter a state of
      suspended animation known as torpor. A major goal of torpor research is to
      determine mechanisms that integrate environmental cues, gene expression and
      metabolism to produce periods of torpor lasting from hours to weeks. Recent
      discoveries spanning the Metazoa suggest that sirtuins, the mammalian circadian
      clock, fibroblast growth factor 21 (FGF21) and lipids are involved in torpor
      induction. For example, sirtuins link cellular energy status to the mammalian
      circadian clock, oxidative stress and metabolic fuel selection. In this review,
      we discuss how these recent discoveries form a new hypothesis linking changes in
      the physical environment with changes in the expression of genes that regulate
      torpor induction.

PMID- 19864162
TI  - Takotsubo cardiomyopathy and coronary vasospasm during orthotopic liver
      transplantation: separate entities or common mechanism?

PMID- 19864163
TI  - Single-ventricle patient: pathophysiology and anesthetic management.

PMID- 19864161
TI  - Research reporting standards for image-guided ablation of bone and soft tissue
      tumors.

PMID- 19864164
TI  - Pre-implantation basiliximab reduces incidence of early acute rejection in
      pediatric heart transplantation.
AB  - BACKGROUND: Basiliximab is an anti-CD25 monoclonal antibody used as induction
      therapy in solid-organ transplantation. In this study we aim to determine whether
      pre-operative administration of basiliximab is beneficial in preventing early
      heart allograft rejection. METHODS: In this investigation we assess the effect of
      pre-implantation basiliximab on CD25 count and on acute rejection in children
      undergoing cardiothoracic transplantation. The notes of all children undergoing
      cardiothoracic transplantation at the Great Ormond Street Hospital between
      January 2000 and June 2007 were retrospectively reviewed. One hundred twenty-one
      heart transplant recipients were included: 29 patients did not receive
      basiliximab; 33 patients received basiliximab after coming off cardiopulmonary
      bypass (CPB); and 59 patients received basiliximab prior to organ implantation.
      RESULTS: All patients receiving basiliximab had an effectively suppressed CD25
      count (<0.2%) on Days 1 and 10 post-transplant. Freedom from Grade 3A or greater
      rejection in the first year was significantly greater in the pre-implantation
      basiliximab group than in the post-implantation and no-basiliximab groups (95%,
      70% and 72%, respectively; p = 0.02). Induction regimen was the only significant
      explanatory variable after multivariate Cox regression. CONCLUSIONS: The results
      of this study confirm that basiliximab is effective at suppressing CD25 count
      whether given pre- or post-CPB. Basiliximab before transplantation appeared to
      reduce acute rejection, whereas post-CPB administration did not suggest similar
      effects. These findings require independent validation in randomized trials and
      further studies should seek to mechanistically delineate these observations.

PMID- 19864165
TI  - Clinical outcomes after cardiac transplantation in muscular dystrophy patients.
AB  - BACKGROUND: Patients with muscular dystrophy are at risk of developing a dilated
      cardiomyopathy and can progress to advanced heart failure. At present, it is not
      known whether such patients can safely undergo cardiac transplantation. METHODS:
      This was a retrospective review of the Cardiac Transplant Research Database, a
      multi-institutional registry of 29 transplant centers in the United States, from
      the years 1990 to 2005. The post-cardiac transplant outcomes of 29 patients with
      muscular dystrophy were compared with 275 non-muscular dystrophy patients with
      non-ischemic cardiomyopathy, matched for age, body mass index, gender, and race.
      RESULTS: Becker's muscular dystrophy was present in 52% of the patients. Survival
      in the muscular dystrophy patients was similar to the controls at 1 year (89% vs
      91%; p = 0.5) and at 5 years (83% vs 78%; p = 0.5). The differences in rates of
      cumulative infection, rejection, or allograft vasculopathy between the 2 groups
      were not significant (p > 0.5 for all comparisons). CONCLUSIONS: Recognizing the
      limitations of the present investigation (ie, selection bias and data lacking in
      the functional capacity of the muscular dystrophy patients), the current study
      suggests that the clinical outcomes after cardiac transplantation in selected
      patients with muscular dystrophy are similar to those seen in age-matched
      patients with non-ischemic cardiomyopathy.

PMID- 19864166
TI  - High-density lipoprotein cholesterol levels and risk of death in chronic heart
      failure patients referred for heart transplant evaluation.

PMID- 19864167
TI  - Novel loci interacting epistatically with bone morphogenetic protein receptor 2
      cause familial pulmonary arterial hypertension.
AB  - BACKGROUND: Familial pulmonary arterial hypertension (FPAH) is a rare, autosomal
      dominant, inherited disease with low penetrance. Mutations in the bone
      morphogenetic protein receptor 2 (BMPR2) have been identified in at least 70% of
      FPAH patients. However, the lifetime penetrance of these BMPR2 mutations is 10%
      to 20%, suggesting that genetic and/or environmental modifiers are required for
      disease expression. Our goal in this study was to identify genetic loci that may
      influence FPAH expression in BMPR2 mutation carriers. METHODS: We performed a
      genome-wide linkage scan in 15 FPAH families segregating for BMPR2 mutations. We
      used a dense single-nucleotide polymorphism (SNP) array and a novel multi-scan
      linkage procedure that provides increased power and precision for the
      localization of linked loci. RESULTS: We observed linkage evidence in four
      regions: 3q22 ([median log of the odds (LOD) = 3.43]), 3p12 (median LOD) = 2.35),
      2p22 (median LOD = 2.21), and 13q21 (median LOD = 2.09). When used in conjunction
      with the non-parametric bootstrap, our approach yields high-resolution to
      identify candidate gene regions containing putative BMPR2-interacting genes.
      Imputation of the disease model by LOD-score maximization indicates that the 3q22
      locus alone predicts most FPAH cases in BMPR2 mutation carriers, providing strong
      evidence that BMPR2 and the 3q22 locus interact epistatically. CONCLUSIONS: Our
      findings suggest that genotypes at loci in the newly identified regions,
      especially at 3q22, could improve FPAH risk prediction in FPAH families. We also
      suggest other targets for therapeutic intervention.

PMID- 19864168
TI  - Utility of levetiracetam in patients with subarachnoid hemorrhage.
AB  - PURPOSE: To determine the utility and tolerability of levetiracetam (LEV)
      compared to phenytoin (PHT) in preventing clinical seizures in patients with
      subarachnoid hemorrhage (SAH). METHODS: Utility and tolerability of PHT and LEV
      in patients with SAH were determined by the occurrence of breakthrough clinical
      seizures or adverse events necessitating a change of medication. Comparisons were
      performed with Chi-square tests. RESULTS: All 176 patients were initially treated
      with PHT. No breakthrough clinical seizures occurred. In 70 (39.8%) patients, PHT
      was replaced with LEV due to adverse events including elevation of transaminases,
      thrombocytopenia, unexplained fever, rash, gastrointestinal disturbance, and
      worsening mental status. After switching to LEV, all adverse effects resolved
      except gastrointestinal disturbance and worsening mental status in 4 patients.
      Adverse events occurred more often in patients taking PHT. CONCLUSIONS: In
      patients with SAH, LEV appears to have superior tolerability compared to PHT.

PMID- 19864169
TI  - Imaging of multiphase fluid saturation within a porous material via sodium NMR.
AB  - We present in this paper a method to monitor multiphase fluid core saturation
      through measurement of the sodium NMR signal. In a rock core saturated with water
      and oil, sodium will be present only in the water phase, and therefore can be
      used to separate the two fluids. Two dimensional sodium images were taken to
      monitor the movement of brine into oil saturated rock cores. The measured fluid
      exchange agrees well with expected behavior from traditional core analysis
      methods. Indications of damage to the rock structure can be seen from the
      patterns of fluid imbibition.

PMID- 19864170
TI  - [Using information technology to improve drug safety in primary care].
AB  - PURPOSE: To help family doctors to detect and prevent problems related to drug
      drug interactions in order to attain a higher quality prescription and an
      improvement in patient safety. METHODS: Uncontrolled study of an intervention
      based on quality evaluation and improvement methods. SETTING: Two health areas in
      Murcia Region (Spain). PATIENTS: Subjects appointed to 139 family doctors
      regularly using electronic clinical records (including doctors who were producing
      over 100 electronic prescriptions per week: 188,953 subjects and 334.088
      prescriptions at the start, and 202,988 subjects and 335.198 prescriptions at the
      end of study). INTERVENTION: (1) A software able to collect patients who had
      clinically important drug-drug interactions those that should be avoided (BOT
      I+II) was designed. (2) A report on these interactions was drawn up and delivered
      periodically to every single doctor, including patient identification and
      information on the drugs involved, possible consequences, and recommendations
      about what to do. (3) Clinical and educative sessions given by a trained
      pharmacist were carried out in doctors' health centre coinciding with their
      delivery. RESULTS: Drug-drug interactions pre-intervention: prevalence 1.29%; by
      patient at risk 6.57%; by doctor 20.2. Post-intervention: prevalence 1.06%
      (improvement 17.6%, P<.000001), by patient at risk 5.17% (improvement 21.4%,
      P<.000001), by doctor 17.7 (improvement 12.1, P<.001). CONCLUSIONS: Developing
      this technology leads to progress in patient safety, therefore it should be
      extended to all our family doctors. Other technologies such as an electronic
      alert when prescribing should be considered, particularly for either higher
      frequency or important consequences interactions.

PMID- 19864171
TI  - Numerical simulation of the effect of time-to-loading on peri-implant bone.
AB  - PURPOSE: To evaluate the effect of time-to-loading on trabecular bone around
      single-tooth dental implants using numerical solutions based on computer models.
      MATERIALS AND METHODS: A global model with a coarse mesh carrying a Straumann
      dental implant (043.033S; Institut Straumann, Basel, Switzerland) was created. A
      region of interest in trabecular bone was defined to study a localized part of
      the global model with a refined mesh. Time-to-loading submodels to simulate 2h, 4
      days, 1, 4, 6 and 12 wks of trabecular bone-healing status were designed and
      created. Bone types were considered in the simulation by different elastic bone
      properties. A 100-N oblique static load was applied. Maximum and minimum
      principal stresses were calculated and visualized. RESULTS: Bone types with
      higher elastic moduli experienced higher stress levels. Changes in the quality
      and quantity of bone at the bone-implant interface did not affect the overall
      stress distribution. Peri-implant bone with a higher elastic modulus preserved
      the stress increase at the implant-bone interface. DISCUSSION: Reduced bone
      contact may not have a prevailing effect over bone quality and quantity on stress
      generation at the peri-implant bone. CONCLUSION: Time-to-loading of single-tooth
      implants may not differ in terms of load distributions in neighboring peri
      implant bone.

PMID- 19864172
TI  - The effect of psychotherapy in patients with PD: a controlled study.
AB  - The purpose of this study was to evaluate whether group psychotherapy was
      effective in improving of quality of life and would decrease the symptoms of
      anxiety and depression in Parkinson's disease patients. Sixteen subjects, with
      idiopathic Parkinson's disease recruited from the school clinical
      Hospital/UNICAMP. Were randomly divided in to two groups, experimental and
      control. Parkinson's Disease and Quality of Life - PDQL; Beck Depression
      Inventory - BDI; State-Trait-Anxiety Inventory - STAI were used to evaluate the
      patients. The statistical analysis showed significant effect of the interaction
      group vs. time in depression (0.0009), anxiety (<0.0001) and QuoL (0.0018) and
      positive changes in depression (0.0029), anxiety (0.0009) and QuoL (0.0047) for
      the treated group.

PMID- 19864173
TI  - Association study of GATA-2 transcription factor gene (GATA2) polymorphism and
      Parkinson's disease.
AB  - It was shown that high levels of alpha-synuclein in substantia nigra are
      essential in pathogenesis of Parkinson disease (PD), and SNCA expression in
      neurons is controlled by GATA-2 transcription factor, which plays also crucial
      role in central nervous system development, and erythroid cells differentiation.
      Recently, significant association of two GATA2 SNPs with early-onset coronary
      artery disease has been presented. In this case-control study we tested a
      hypothesis that polymorphism of GATA2 gene may be associated with sporadic PD.
      Five tag SNPs within GATA2 gene (rs2860228:G > A, rs2335052:G > A, rs11717152:A >
      C, rs2713604:G > A, and rs3803:C > T) were investigated in 368 PD patients and
      349 controls of Caucasian origin from Poland. We did not find any significant
      differences in the GATA2 allele and genotype frequencies between PD cases and
      controls, for individual SNPs, neither in haplotype analysis. Elevated frequency
      of rs3803T allele was observed in early-onset PD patients (vs. controls and vs.
      late-onset PD), but this difference was not significant (0.05 < p < 0.1). We
      conclude that GATA2 polymorphism is not an important risk factor for sporadic PD
      in Caucasians.

PMID- 19864174
TI  - Model substrates for studies of cell mobility.
AB  - Cells do not live in static surroundings, they exist in highly evolving dynamic
      environments. During cell adhesion and migration, cells adapt and communicate to
      their environment by numerous methods ranging from differentiation, gene
      expression, growth, and apoptosis. How and when cells determine to adhere,
      polarize, and migrate is important to a number of fundamental biological
      processes such as wound healing, metastasis, inflammation, and development. In
      order to elucidate the spatial and temporal mechanisms of these important complex
      processes on a molecular basis, several research groups have generated model
      substrates that can present nanopatterned ligands, well-defined gradients of
      ligands and surfaces that can be dynamically modulated where the interaction
      between cell and material is defined at the molecular level.

PMID- 19864175
TI  - Plant cuticles shine: advances in wax biosynthesis and export.
AB  - The plant cuticle is an extracellular lipid structure deposited over the aerial
      surfaces of land plants, which seals the shoot and protects it from biotic and
      abiotic stresses. It is composed of cutin polymer matrix and waxes, produced and
      secreted by epidermal cells. The use of forward and reverse genetic approaches in
      Arabidopsis has led to the identification of enzymes involved in fatty acid
      elongation and biosynthesis of wax components, as well as transporters required
      for lipid delivery to the cuticle. However, major questions concerning alkane
      formation, intracellular and extracellular wax transport, regulation of wax
      deposition, and assembly of cuticular components into a functional cuticle remain
      to be resolved.

PMID- 19864177
TI  - Self-signalling and self-fusion in filamentous fungi.
AB  - The formation of interconnected hyphal networks is central to the organisation
      and functioning of the filamentous fungal colony. It is brought about by the
      fusion of specialised hyphae during colony initiation and mature colony
      development. These hyphae are normally genetically identical, and hence this
      process is termed hyphal self-fusion. The conidial anastomosis tube (CAT)
      functions in forming networks of conidial germlings during colony initiation.
      This hyphal type in Neurospora crassa is being used as a model for studies on
      hyphal self-signalling and self-fusion in filamentous fungi. Extraordinary new
      insights into the process of self-signalling that occurs during CAT self-fusion
      have recently been revealed by live-cell imaging of genetically engineered
      strains of N. crassa. A novel form of signalling involving the oscillatory
      recruitment of signal proteins to CAT tips that are communicating and growing
      towards each other has been observed. This 'ping-pong' mechanism operates over a
      very short time scale and comparisons with non-self-signalling during yeast cell
      mating indicate that this mechanism probably does not involve transcriptional
      regulation. It is proposed that this mechanism has evolved to increase the
      efficiency of fusion between genetically identical cells that are non-motile.

PMID- 19864176
TI  - Prion dynamics and the quest for the genetic determinant in protein-only
      inheritance.
AB  - According to the prion hypothesis, proteins may act in atypical roles as genetic
      elements of infectivity and inheritance by undergoing self-replicating changes in
      physical state. While the preponderance of evidence strongly supports this
      concept particularly in fungi, the detailed mechanisms by which distinct protein
      forms specify unique phenotypes are emerging concepts. A particularly active area
      of investigation is the molecular nature of the heritable species, which has been
      probed through genetic, biochemical, and cell biological experimentation as well
      as by mathematical modeling. Here, we suggest that these studies are converging
      to implicate small aggregates composed of prion-state conformers as the
      transmissible genetic determinants of protein-based phenotypes.

PMID- 19864178
TI  - Effect of KCl addition on crystal growth and spectral properties of glycine
      single crystals.
AB  - Glycine usually crystallizes as the metastable alpha-polymorph from pure aqueous
      solution. The polymorph, gamma-form of glycine can be crystallized only in
      presence of additive. In the present work, gamma-glycine has been crystallized by
      using potassium chloride (KCl) as additive at ambient temperature by solvent
      evaporation method. The form of crystallization is confirmed by X-ray powder
      diffraction method. Spectroscopic and thermal studies have been carried out for
      analyzing the presence of functional groups, thermal stability and decomposition
      of the sample. The results indicate that the KCl is doped into the gamma-glycine.
      The optical transparency of the gamma-glycine in the ultraviolet-visible region
      has been studied by recording the optical transmission spectrum. Second harmonic
      generation (SHG) conversion efficiency has been estimated as 120 mV and the
      output power by the crystal is less than that of potassium dihydrogen phosphate
      crystal.

PMID- 19864179
TI  - Vibrational spectra, ab initio/DFT electronic structure calculations, and normal
      coordinate analysis of 2-bromo-5-fluorobenzaldehyde.
AB  - FT-IR (4000-400 cm(-1)) and FT-Raman (3500-50 cm(-1)) spectral measurements of
      solid samples of 2-bromo-5-fluorobenzaldehyde (BFB) have been done. Ab initio
      (RHF/6-311G*) and DFT (B3LY/6-311G* and B3PW91/6-311G*) calculations have been
      performed giving energies, optimized structures, harmonic vibrational
      frequencies, depolarization ratios, infrared intensities, Raman activities and
      atomic displacements. Furthermore force field calculations have been performed by
      normal coordinate analysis. Force field calculations showed that several normal
      modes are mixed in terms of the internal coordinates. A complete assignment of
      the observed spectra, based on spectral correlations, electronic structure and
      normal coordinate analysis, has been proposed. Optimization leads to C(S)
      symmetry with O-trans and O-cis isomers, with respect to aldehydic oxygen and
      bromine, with O-trans-isomer as the low energy stable form. The energy difference
      between the two isomers is 2.95084 kcal/mol. The results of the calculations have
      been used to simulate IR and Raman spectra for BFB that showed excellent
      agreement with the observed spectra. The SQM method, which implies multiple
      scaling of the ab initio and DFT force fields has been shown superior to the
      uniform scaling approach.

PMID- 19864180
TI  - FT-IR and FT-Raman vibrational assignment of 2-bromobenzoic acid with the help of
      ab initio and DFT calculations.
AB  - The vibrational spectra of 2-bromobenzoic acid (2BBA) have been experimentally
      recorded (FT-IR and FT-Raman) and compared with the harmonic vibrational
      frequencies calculated at HF and B3LYP level of theories using 6-311+G(d,p) basis
      set with appropriate scaling factors. The XRD geometrical parameters show
      satisfactory agreement with the theoretical prediction at Hartree-Fock and B3LYP
      levels. The scaled vibrational frequencies at B3LYP/6-311+G(d,p) seem to coincide
      with the experimentally observed values with acceptable deviations. The
      theoretical spectrograms (IR and Raman) have been constructed and compared with
      the experimental FT-IR and FT-Raman spectra.

PMID- 19864181
TI  - Sequential injection kinetic spectrophotometric determination of quaternary
      mixtures of carbamate pesticides in water and fruit samples using artificial
      neural networks for multivariate calibration.
AB  - A new analytical method was developed for the simultaneous kinetic
      spectrophotometric determination of a quaternary carbamate pesticide mixture
      consisting of carbofuran, propoxur, metolcarb and fenobucarb using sequential
      injection analysis (SIA). The procedure was based upon the different kinetic
      properties between the analytes reacted with reagent in flow system in the non
      stopped-flow mode, in which their hydrolysis products coupled with diazotized p
      nitroaniline in an alkaline medium to form the corresponding colored complexes.
      The absorbance data from SIA peak time profile were recorded at 510 nm and
      resolved by the use of back-propagation-artificial neural network (BP-ANN)
      algorithms for multivariate quantitative analysis. The experimental variables and
      main network parameters were optimized and each of the pesticides could be
      determined in the concentration range of 0.5-10.0 microg mL(-1), at a sampling
      frequency of 18 h(-1). The proposed method was compared to other
      spectrophotometric methods for simultaneous determination of mixtures of
      carbamate pesticides, and it was proved to be adequately reliable and was
      successfully applied to the simultaneous determination of the four pesticide
      residues in water and fruit samples, obtaining the satisfactory results based on
      recovery studies (84.7-116.0%).

PMID- 19864184
TI  - Developing discharge practice through education: module development, delivery and
      outcomes.
AB  - In England (UK) the discharge of patients from hospital is a source of constant
      scrutiny from primary care trusts in order to reduce the patient length of stay
      in Hospital. To support nurses in practice a part time, post registration
      discharge practice education module was developed entitled Facilitating Timely
      Patient Discharge. It was the first of its kind to be accredited at degree level
      (level 6) during 2006. University evaluation of the module involved an academic
      assignment based on a 3000 word case study. Projects in practice were integrated
      to enable the students to apply theories to clinical practice. This aspect was
      driven by an organisational impetus to demonstrate learning back in practice to
      the benefit of Heart of England Foundation Trust (HEFT). Students self assessed
      their individual ability pre and post the discharge module using questionnaires
      citing 17 areas of discharge practice analysing knowledge and ability. They
      demonstrated an increase in knowledge and ability in key areas such as;
      'understanding complex discharge' and 'teaching discharge practice to peers'.
      Although these were not formally included in the outcomes or evaluations they may
      inform future module development and design of delivery. The questionnaires were
      designed and developed with support for projects in practice from the Foundation
      of Nursing Studies in London.

PMID- 19864183
TI  - The dynamics of mutations associated with anti-malarial drug resistance in
      Plasmodium falciparum.
AB  - The evolution of resistance in Plasmodium falciparum against safe and affordable
      drugs such as chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) is a major
      global health threat. Investigating the dynamics of resistance against these
      antimalarial drugs will lead to approaches for addressing the problem of
      resistance in malarial parasites that are solidly based in evolutionary genetics
      and population biology. In this article, we discuss current developments in
      population biology modeling and evolutionary genetics. Despite great advancements
      achieved in the past decade, understanding the complex dynamics of mutations
      conferring drug resistance in P. falciparum requires approaches that consider the
      parasite population structure among other demographic processes.

PMID- 19864182
TI  - Innate immune responses to influenza A H5N1: friend or foe?
AB  - Avian influenza A H5N1 remains unusual in its virulence for humans. Although
      infection of humans remains inefficient, many of those with H5N1 disease have a
      rapidly progressing viral pneumonia that leads to acute respiratory distress
      syndrome and death, but its pathogenesis remains an enigma. Comparison of the
      virology and pathogenesis of human seasonal influenza viruses (H3N2 and H1N1) and
      H5N1 in patients, animal models and relevant primary human cell cultures is
      instructive. Although the direct effects of viral replication and differences in
      the tropism of the virus for cells in the lower respiratory tract clearly
      contribute to pathogenesis, we focus here on the possible contribution of the
      host innate immune response in the pathogenesis of this disease.

PMID- 19864185
TI  - Xanthogranulomatous pyelonephritis in pediatric patients: case report and review
      of literature.
AB  - Xanthogranulomatous pyelonephritis (XPN) is an unusual and rare form of chronic
      renal suppuration. XPN is often mistaken for renal malignancy; hence nephrectomy
      is commonly performed and the diagnosis confirmed by histopathology. Recent
      advances in imaging have allowed the radiological features to be characterized,
      such that routine nephrectomy is avoided. Approximately 240 cases of XPN have
      been reported in children. We report a 17-year-old female who presented with a 2
      month history of increasing abdominal pain and intermittent episodes of increased
      frequency and dysuria. Plain antero-posterior radiograph of the abdomen revealed
      a left staghorn calculus. Computed tomography scan with intravenous contrast
      revealed a low-density inflammatory area and reduced cortical dye uptake on the
      left renal parenchyma as compared to the opposite side. A dimercapto-succinic
      acid renal scan revealed that the affected kidney contributed 18% of differential
      function. A diagnosis of XPN was made. The patient underwent percutaneous
      nephrostomy tube placement in an attempt to salvage the kidney. The patient
      eventually failed conservative management. Our review of the literature suggests
      that medical management has worked in some focal XPN cases, but has not been
      sufficiently tested in diffuse XPN.

PMID- 19864186
TI  - Cancer genetics and reproduction.
AB  - Cancers of the reproductive organs (i.e., ovaries, uterus and testes), like other
      cancers, occur as a result of a multi-stage interaction of genetic and
      environmental factors. A small proportion of cancers of the reproductive organs
      occur as part of a recognised cancer syndrome, as a result of inheritance of
      mutations in highly penetrant cancer susceptibility genes (e.g., BRCA1, BRCA2,
      MLH1 or MSH2). Recognition of individuals and families with inherited cancer
      predisposition syndromes and individuals at high risk due to familial cancer
      clustering is fundamentally important for the management and treatment of the
      current cancer and for future prevention of further cancers for the individual
      and their extended family.

PMID- 19864187
TI  - Enhancing antiepileptic drug adherence: a randomized controlled trial.
AB  - Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and
      increases the risk of status epilepticus and sudden unexplained death in
      epilepsy. This randomized controlled trial was designed to demonstrate whether an
      implementation intention intervention involving the completion of a simple self
      administered questionnaire linking the intention of taking medication with a
      particular time, place, and other activity can improve AED treatment schedule
      adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1
      month monitoring period with an objective measure of tablet taking (electronic
      registration of pill bottle openings, Medication Event Monitoring System [MEMS]).
      Intervention participants showed improved adherence relative to controls on all
      three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct
      dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%)
      (P<0.01). The implementation intention intervention may be an easy-to-administer
      and effective means of promoting AED adherence.

PMID- 19864188
TI  - Current status and outcomes of catheter ablation for atrial fibrillation.
AB  - Catheter ablation has evolved as an effective treatment modality in patients with
      AF. In this review, the rationale and outcomes of ablation strategies targeting
      various mechanisms of AF based on our current understanding are discussed. Likely
      mechanisms responsible for the therapeutic effects of these approaches are
      reviewed.

PMID- 19864189
TI  - Complications during catheter ablation of atrial fibrillation: identification and
      prevention.
AB  - Complications are inherent to any invasive procedure. The list of complications
      associated with catheter ablation of atrial fibrillation has steadily increased
      with the increase in complexity and the number of procedures performed over the
      years. This review focuses on strategies for prevention, and techniques for rapid
      detection and management of these complications.

PMID- 19864190
TI  - Minimally invasive surgical atrial fibrillation ablation: patient selection and
      results.
AB  - Minimally invasive surgical atrial fibrillation ablation (MISAA) is an emerging
      alternative to catheter ablation and the full surgical maze procedure for
      nonpharmacologic treatment of atrial fibrillation. MISAA offers the potential to
      provide highly effective pulmonary vein isolation, exclusion of the left atrial
      appendage, and extensive ablation of the ganglionic plexuses and the ligament of
      Marshall in a single procedure. We review the safety and efficacy of MISAA,
      discuss considerations for optimal patient selection for MISAA, and review the
      advantages/disadvantages of MISAA compared with catheter ablation and the maze
      procedure.

PMID- 19864191
TI  - Quantification of drugs of abuse and some stimulants in hair samples by liquid
      chromatography-electrospray ionization ion trap mass spectrometry.
AB  - A qualitative and quantitative method for the analysis of drugs of abuse (cocaine
      and benzoylecgonine, opiates) and some stimulants in human hair was developed and
      validated. Hair samples were incubated with phosphate buffer (pH 5.0), chosen as
      the extraction medium, extracted with Bond Elut Certify cartridges and analyzed
      by LC-MS-MS and LC-MS(3) as confirmation for positive results. The method proved
      to be specific, accurate and precise across the calibration range (0.1-30 ng/mg)
      where good linearity was observed. Total extraction recovery, intra-assay
      accuracy and precision, limits of detection and limits of quantitation were
      estimated. The method was successfully applied to the analysis of hair samples
      collected from drug abusers and it was suitable for routine analytical
      applications in the Antidoping Laboratory of Public Health Laboratory.

PMID- 19864192
TI  - Highly sensitive determination of HCV protease inhibitors boceprevir (SCH 503034)
      and telaprevir (VX 950) in human plasma by LC-MS/MS.
AB  - The purpose of this study was to develop a specific and highly sensitive method
      based on fast sample preparation and LC-MS/MS techniques for the determination of
      the HCV protease inhibitors boceprevir (SCH 503034) and telaprevir (VX 950) in
      human plasma. Boceprevir, telaprevir and the internal standard dimethylcelecoxib
      were separated on a Luna C18 column (150 mm x 2.0 mm I.D., 5 microm particle
      size) under gradient conditions with a mobile phase A consisting of water/ammonia
      solution (25%) (100:0.05, v/v) and mobile phase B consisting of methanol/ammonia
      solution (25%) (100:0.05, v/v) and a chromatographic run time of 11 min. The
      lower limit of quantification (LLOQ) of boceprevir and telaprevir is 0.25 pg on
      column (25 pg/mL at injection volume of 10 microL). The method possesses a
      reliable calibration range of 0.025-2.5 ng/mL. Due to the dilution of real life
      plasma samples by a factor of 10 during the precipitation process the method is
      suitable to quantify boceprevir and telaprevir at a concentration range of 0.25
      25 ng/mL. Variations in accuracy and intraday and interday precision (n=6 for
      each concentration) were <15% over the whole range of calibration. For the first
      time, a rapid, specific, sensitive, accurate and reproducible LC-MS/MS method in
      human plasma has been developed and validated. It is suitable to quantify the
      concentrations of the hepatitis C virus protease inhibitors boceprevir and
      telaprevir in human plasma.

PMID- 19864193
TI  - [Diagnosis and treatment guidelines for difficult-to-control asthma in children].
AB  - Children suffering from difficult-to-control asthma (DCA) require frequent
      appointments with their physician, complex treatment regimes and often admissions
      to hospital. Less than 5% of the asthmatic population suffer this condition. DCA
      must be correctly characterised to rule out false causes of DCA and requires
      making a differential diagnosis from pathologies that mimic asthma, comorbidity,
      environmental and psychological factors, and analysing the factors to determine
      poor treatment compliance. In true DCA cases, inflammation studies (exhaled
      nitric oxide, induced sputum, broncho-alveolar lavage and bronchial biopsy),
      pulmonary function and other clinical aspects can classify DCA into different
      phenotypes which could make therapeutic decision-making easier.

PMID- 19864194
TI  - Community-associated methicillin-resistant Staphylococcus aureus disease in
      children in Taiwan: the importance of antibiotic stewardship.

PMID- 19864195
TI  - Risk factors for dementia.
AB  - Dementia is a complex human disease. The incidence of dementia among the elderly
      population is rising rapidly worldwide. In the United States, Alzheimer's disease
      (AD) is the leading type of dementia and was the fifth and eighth leading cause
      of death in women and men aged > or = 65 years, respectively, in 2003. In Taiwan
      and many other counties, dementia is a hidden health issue because of its
      underestimation in the elderly population. In Western countries, the prevalence
      of AD increases from 1-3% among people aged 60-64 years to 35% among those aged >
      85 years. In Taiwan, the prevalence of dementia for people aged > or = 65 years
      was 2-4% by 2000. Therefore, it is important to identify protective and risk
      factors for dementia to prevent this disease at an early stage. Several factors
      are related to dementia, e.g. age, ethnicity, sex, genetic factors, physical
      activity, smoking, drug use, education level, alcohol consumption, body mass
      index, comorbidity, and environmental factors. In this review, we focus on
      studies that have evaluated the association between these factors and the risk of
      dementia, especially AD and vascular dementia. We also suggest future research
      directions for researchers in dementia-related fields.

PMID- 19864196
TI  - Genotyping, plasmid analysis, and antimicrobial susceptibility of Salmonella
      enterica serotype Enteritidis isolates from humans and chickens in central
      Taiwan.
AB  - BACKGROUND/PURPOSE: Salmonella enterica serotype Enteritidis (SE) is the most
      frequent etiological agent of human salmonellosis. The molecular epidemiology and
      antimicrobial susceptibility of human and chicken isolates of SE were examined.
      METHODS: A total of 27 human and 40 chicken isolates of SE were collected in 2005
      2006. We examined these isolates by antimicrobial susceptibility testing, pulsed
      field gel electrophoresis (PFGE), and plasmid analysis. RESULTS: Most isolates
      were susceptible to the seven antibiotics tested, except chicken isolates in
      2005, which showed 70% resistance to streptomycin and 75% to tetracycline. There
      were six plasmid profiles identified among these isolates. Almost all isolates
      (97%) harbored the 60-kb serotype-specific virulence plasmid. PFGE using XbaI
      digestion separated human isolates into eight subtypes (1a-1h) and chicken
      isolates into four subtypes (1a-1c and 1g). In 2005, 1a and 1c were predominant
      for human isolates and 1a for chicken isolates. However, in 2006, 1a and 1c
      remained predominant for human isolates and 1b and 1c for chicken isolates. Most
      1b and 1c isolates belonged to plasmid type 2 or 4. Correlation between plasmid
      patterns and PFGE subtypes was obtained between a 36-kb plasmid and 1b and
      between another 3.6-kb plasmid and 1a. CONCLUSION: Plasmid profiling and PFGE
      were efficient for discriminating SE isolates from different sources. Our data
      support the notion that SE is transmitted from chickens to humans, presumably
      through the food chain, but it appears that chickens are not the sole reservoir
      for human infection with SE in Taiwan SE remained susceptible to most
      antimicrobial agents.

PMID- 19864197
TI  - Exhaled nitric oxide in a Taiwanese population: age and lung function as
      predicting factors.
AB  - BACKGROUND/PURPOSE: The fractional concentration of exhaled nitric oxide (FE(NO))
      has been reported to be elevated in asthma and many other lung diseases. The
      present study investigated reference values and determinants of FE(NO) in a
      Taiwanese non-smoking, healthy adult population. METHODS: We used a
      chemiluminescence analyzer according to American Thoracic Society/European
      Respiratory Society recommendations to measure FE(NO) values in 356 adults who
      received a health check-up and a detailed respiratory questionnaire at Taichung
      Veterans General Hospital, Taiwan. Among the volunteers, 249 fulfilled our
      definition of healthy adults: no history of smoking or physician-diagnosed
      asthma; no recent upper airway infection; no chronic respiratory symptoms; and no
      allergic rhinitis and urticaria. RESULTS: Among the 249 non-smoking and non
      asthmatic adults, the mean (5th to 95th percentile reference range) FE(NO) was
      27.9 (12.5-58.0) parts per billion. In multivariate regression analyses, age and
      lung function (forced vital capacity or forced expiratory volume in 1 second)
      were associated positively with FE(NO) values. Sex, height, weight, and ambient
      NO values were not associated significantly with FE(NO) values. CONCLUSION: Age
      and lung function were predictors of FE(NO) in this population, and these factors
      should be considered for clinical applications of FE(NO) measurements.

PMID- 19864198
TI  - Key process indicators of mortality in the implementation of protocol-driven
      therapy for severe sepsis.
AB  - BACKGROUND/PURPOSE: Severe sepsis and septic shock are life-threatening
      disorders. Integrating treatments into a bundle strategy has been proposed to
      facilitate timely resuscitation, but is difficult to implement. We implemented
      protocol-driven therapy for severe sepsis, and analyzed retrospectively the key
      process indicators of mortality in managing sepsis. METHODS: Continuous quality
      improvement was begun to implement a tailored protocol-driven therapy for sepsis
      in a 24-bed respiratory intensive care unit (RICU) of Taichung Veterans General
      Hospital from January 2007 to February 2008. Patients, who were admitted to the
      RICU directly, or within 24 hours, were enrolled if they met the criteria for
      severe sepsis and septic shock. Disease severity [Acute Physiology and Chronic
      Health Evaluation (APACHE) II and lactate level], causes of sepsis, comorbidity
      and site of sepsis onset were recorded. Process-of-care indicators included
      resuscitation time (Tr-s), RICU bed availability (Ti-s) and the ratio of
      completing the elements of the protocol at 1, 2, 4 and 6 hours. The structure and
      process-of-care indicators reflated to mortality at 7 days after RICU admission
      and at RICU discharge were identified retrospectively. RESULTS: Eighty-six
      patients (mean age, 71 +/- 14 years, 72 men, 14 women, APACHE II, 25.0 +/- 7.0)
      were enrolled. APACHE II scores and lactate levels were higher for mortality than
      survival at 7 days after RICU admission (p < 0.01). For the process-of-care
      indicators, Ti-s (562.2 +/- 483.3 vs.1017.3 +/- 557.8 minutes, p = 0.03) and Tr-s
      (60.7 +/- 207.8 vs. 248.5 +/- 453.1 minutes, p = 0.07) were shorter for survival
      than mortality at 7 days after RICU admission. The logistic regression study
      showed that Tr-s was an important indicator. The ratio of completing the elements
      of protocols at 1, 2, 4 and 6 hours ranged from 70% to 90% and was not related to
      mortality. CONCLUSION: Protocol-driven therapy for sepsis was put into clinical
      practice. Early resuscitation and ICU bed availability were key process
      indicators in managing sepsis, to reduce mortality.

PMID- 19864199
TI  - Short-term sulpiride treatment of children and adolescents with Tourette syndrome
      or chronic tic disorder.
AB  - BACKGROUND/PURPOSE: Tourette syndrome (TS) is characterized by motor and vocal
      tics, and its diagnosis is based on clinical criteria. Dopamine-blocking
      neuroleptics are regarded as the most effective drugs for the treatment of TS.
      Sulpiride is a selective dopamine D2 antagonist. However, only one study with a
      large number of patients has reported the effect of treatment of TS with
      sulpiride. The purpose of this study was to evaluate prospectively the effect of
      sulpiride treatment of children and adolescents with TS or chronic tic disorder.
      METHODS: The inclusion criteria were patients who fulfilled the diagnosis of TS
      or chronic tic disorder, and who had not received previous treatment. The
      severity of TS was assessed by the Yale Global Tic Severity Score (YGTSS) every 2
      weeks for a total of 6 weeks. The patients started treatment with low-dose
      sulpiride according to their age on the first visit. The adverse effects of
      sulpiride were evaluated by subjective complaints from the patients themselves or
      their parents. The change in scores between each assessment point was analyzed by
      repeated measures one-way analysis of variance, with SPSS version 12.0 software.
      RESULTS: One hundred and eighty-nine patients were enrolled. Their average age
      was 8.0 +/- 2.5 years (range, 3-15 years). Most patients were male (n = 165,
      87.3%). Six weeks' treatment significantly improved motor tics (p < 0.05), vocal
      tics (p < 0.05) and total YGTSS (p < 0.05). The most commonly encountered adverse
      effect was sedation (n = 31, 16.4%). CONCLUSION: Sulpiride is effective for short
      term treatment of children and adolescents with TS or chronic tic disorder, and
      has few adverse effects.

PMID- 19864200
TI  - Medical expenditure and family satisfaction between hospice and general care in
      terminal cancer patients in Taiwan.
AB  - BACKGROUND/PURPOSE: As the number of terminal cancer patients increases, several
      care models have been adopted to provide better care quality and reduce medical
      expenditure. This study compared inpatient medical expenditure and family
      satisfaction in a hospice ward (HW) and general ward (GW) for terminal cancer
      patients in Taiwan. METHODS: We enrolled terminal cancer patients who were
      admitted and died during the same admission period in a tertiary care hospital in
      Taiwan from January 2003 to December 2005. These patients were allocated into
      three groups: inpatient care in HW alone; inpatient care in GW alone; and
      inpatient care in mixed group (initially in GW, then transferred to HW).
      Inpatient medical expenditure and family satisfaction were compared between the
      three groups. RESULTS: A total of 1942 patients were recruited and allocated into
      HW (n = 292), GW (n = 1511) and mixed (n = 139) groups. The average medical
      expenditure per person or per inpatient day was lower in the HW than the GW or
      mixed group. Subjects who had ever been admitted to the intensive care unit or
      received cardiopulmonary resuscitation in the GW or mixed groups required more
      expenditure on medical care than that in the HW group. Daily medical expenditure
      in the HW group also was much lower than that in the GW and mixed groups, based
      on length of stay and cancer type. The family satisfaction score was
      significantly higher in the mixed and/or HW group than the GW group. CONCLUSION:
      For terminal cancer patients, hospice care can improve family satisfaction while
      reducing medical expenditure in Taiwan.

PMID- 19864201
TI  - PTPN11 mutations in LEOPARD syndrome: report of four cases in Taiwan.
AB  - BACKGROUND/PURPOSE: LEOPARD syndrome (LS) is a rare, autosomal dominant disorder.
      The typical clinical presentation includes multiple lentigines and cardiac
      defects. Mutation analysis of the PTPN11 gene is feasible. We report four cases
      of LS, which were confirmed by molecular genetic study. METHODS: The clinical
      features and mutations of the four patients were summarized. RESULTS: The
      diagnosis of all four patients was made when lentigines appeared during
      childhood. Three cases had hypertrophic cardiomyopathy. No electrocardiographic
      conduction abnormality was noted in any of the cases. Three patients had
      hypertelorism and three had short stature. Two patients, identical twins,
      presented with the atypical phenotype of tongue protrusion and hepatosplenomegaly
      at birth. Twin B had mild mental retardation. Case 4 had moderate hearing
      impairment. Point mutation of the PTPN11 gene was found in all patients.
      CONCLUSION: LS has typical skin manifestations. All patients should undergo a
      comprehensive examination, especially echocardiography and electrocardiography.
      The diagnosis can be confirmed by genetic study.

PMID- 19864202
TI  - Radicular cyst with actinomycotic infection in an upper anterior tooth.
AB  - Actinomycosis is an infection caused by filamentous, branching, Gram-positive
      anaerobic bacteria. It rarely infects the jawbone. This case report describes a
      patient with a left maxillary central incisor with an apical lesion and
      actinomycotic infection. A 23-year-old male patient underwent conventional root
      canal treatment of tooth 21, in a local dental clinic for about 1 year. However,
      percussion pain and a sinus tract that originated from tooth 21 were still
      present after treatment. Nonsurgical root canal treatment of tooth 21 was
      performed again but failed to relieve the symptoms. Therefore, apicoectomy and
      retrograde filling of the apical root canal with mineral trioxide aggregate were
      carried out. Periradicular bony defect was grafted by biocompatible material, and
      postoperative antibiotics (250 mg amoxicillin) were given three times daily for 5
      days. Pathological examination of the removed periapical tissue showed a
      radicular cyst with actinomycosis. At the 9-month postoperative recall, the sinus
      tract had disappeared and radiographic examination showed healing of the apical
      lesion. Periradicular actinomycosis is one important reason for failure of
      nonsurgical endodontic treatment. Clinically, if the tooth shows a recurrent
      sinus tract and poor response to conventional root canal treatment combined with
      antibiotic control, apical actinomycotic infection should be highly suspected,
      and an alternative endodontic surgical approach is needed for successful
      treatment.

PMID- 19864203
TI  - Hypocalcemia and tetany caused by vitamin D deficiency in a child with intestinal
      lymphangiectasia.
AB  - Primary intestinal lymphangiectasia is a rare disease of children, which is
      characterized by chronic diarrhea and complicated with malnutrition, including
      fat-soluble vitamin deficiency. We report a girl aged 4 years and 8 months who
      was diagnosed with the disease by endoscopic duodenal biopsy at 8 months of age.
      She presented initially with chronic diarrhea at 4 months of age. Generalized
      edema with hypoalbuminemia frequently occurred despite regular albumin
      supplements. Multiple vitamins initially were not supplied regularly. Episodes of
      tetany caused by hypocalcemia developed 4 years after the diagnosis of intestinal
      lymphangiectasia. Imaging study (long-bone X-ray and dual-energy X-ray
      absorptiometry) revealed low bone density. Complicated vitamin D deficiency [low
      serum 25-hydroxy vitamin D concentration (< 12.48 mmol/L, the detection limit)]
      and secondary hyperparathyroidism were confirmed via blood testing. Vitamin D
      supplementation for 3 months improved her bone density, secondary
      hyperparathyroidism and frequent tetany. Vitamin D status should be monitored in
      patients with intestinal lymphangiectasia.

PMID- 19864204
TI  - Porcelain factory worker with asbestos-related mesothelioma.
AB  - Malignant mesothelioma is a rare tumor among the general population, but for
      people exposed to asbestos, the lifetime risk is high. A 58-year old man
      presented with suffering from chest pain, upper back pain, shortness of breath,
      and coughing that had continued for several months. A chest X-ray revealed right
      side pleural effusion; however, pleural biopsy from drainage treatment confirmed
      a diagnosis of malignant mesothelioma. According to his occupational and
      environmental history, the patient had worked continuously in a porcelain factory
      for 30 years. The specific characteristics of his work, making asbestos
      wallboards and gaskets, entailed working in high-temperature conditions with a
      high fine-particle content in the atmosphere. The high working temperature caused
      asbestos debris and dust to fall down regularly from the wallboards, however, it
      was not until recently that the patient had started to wear personal protection.
      Asbestos is a significant source of hazardous exposure in old buildings, and this
      case serves as a reminder of the importance of asbestos-related exposure history,
      which facilitated the correct diagnosis of pulmonary malignant mesothelioma.
      Asbestos-containing materials that are now banned or regulated are still present
      in older buildings and remain an exposure hazard; they continue to be a serious
      health concern in many countries.

PMID- 19864205
TI  - [Liver chemoembolization: an update].
AB  - Percutaneous intraarterial techniques for treatment of liver tumors are
      continuously under development. New therapeutic methods are available (such as
      microsphere-encapsulated chemotherapy or yttrium 90 microspheres) and presently
      under evaluation. These methods enlarge the field of indications, i.e. in
      metastasis from colorectal cancer. Hepatocellular carcinoma and metastasis from
      neuroendocrine tumours are the main pathologies favourably responding to
      "conventional" chemoembolization. Thank to controlled studies and meta-analysis
      performed along the last ten years, curative-palliative-as well as adjuvant
      indications for chemoembolization in hepatocellular carcinoma are now
      wellestablished.

PMID- 19864206
TI  - Immunohistochemical and biochemical assay of versican in human sound
      predentine/dentine matrix.
AB  - Aim of this study was to investigate the distribution of versican proteoglycan
      within the human dentine organic matrix by means of a correlative
      immunohistochemical analysis with field emission in-lens scanning electron
      microscope (FEI-SEM), transmission electron microscope (TEM), fluorescence
      microscope (FM) and biochemical assay. Specimens containing dentine and
      predentine were obtained from non carious human teeth and divided in three
      groups: 1) FEI-SEM group: sections were exposed to a pre-embedding
      immunohistochemical procedure; 2) TEM group: specimens were fixed, demineralised,
      embedded and submitted to a post-embedding immunohistochemical procedure; 3) FM
      group: sections mineralised and submitted to a pre-embedding immunohistochemical
      procedure with fluorescence labelling. Specimens were exposed to two different
      antibodies to assay distribution of versican fragments and whole versican
      molecule.Western Blotting analysis of dentine and pulp extracts was also
      performed. The correlative FEI-SEM,TEM and FM analysis revealed positive
      immunoreaction for versican fragments both in predentine and dentine, while few
      gold particles identifying the whole versican molecule were found in predentine
      only under TEM. No labelling of versican whole molecule was detected by FEI-SEM
      and FM analysis. The immunoblotting analysis confirmed the morphological
      findings. This study suggests that in fully developed human teeth versican
      fragments are significant constituents of the human dentine and predentine
      organic matrix, while versican whole molecule can be visualised in scarce amount
      within predentine only. The role of versican fragments within human dentine
      organic matrix should be further elucidated.

PMID- 19864207
TI  - Neurotensin receptor 1 immunoreactivity in the peripheral ganglia and carotid
      body.
AB  - In the present study we investigated, through immunohistochemistry, the presence
      and location of neurotensin receptor 1 (NTR1) in the peripheral ganglia and
      carotid body of 16 humans and 5 rats. In both humans and rats, NTR1 immunostained
      ganglion cells were found in superior cervical ganglia (57.4+/-11.6% and 72.4+/
      11.4%, respectively, p0.05), enteric ganglia (51.9+/-10.4% and 64.6+/-6.1,
      p<0.05), sensory ganglia (69.2+/-10.7% and 73.0+/-13.1%, p>0.05) and
      parasympathetic ganglia (52.1+/-14.1% and 59.4+/-14.0%, p>0.05), supporting a
      modulatory role for NT in these ganglia. Positivity was also detected in 45.6+/
      9.2% and 50.8+/-6.8% of human and rat type I glomic cells, respectively, whereas
      type II cells were negative. Our findings suggest that NT produced by type I
      cells acts in an autocrine or paracrine way on the same cell type, playing a
      modulatory role on chemoception.

PMID- 19864208
TI  - Endocrine cells in atresic chick embryo intestine: histochemical and
      immunohistochemical study.
AB  - Intestinal motility disorders are an important problem in the postoperative
      management of patients with intestinal atresia. Intestinal motility could be
      initiated by luminal factors that activate intrinsic and extrinsic primary
      afferent nerves involved in the peristaltic reflex. Endocrine cells act as a key
      point, because they transfer information regarding the intestinal contents and
      intraluminal pressure to nerve fibers lying in close proximity to the basolateral
      surface of the epithelium. In chick embryo, experimental intestinal atresia is
      associated with disorders in the development of the enteric nervous system,
      related to the severity of intestinal dilation. Our aim was to investigate the
      distribution pattern of endocrine cells in the developing endocrine system of
      chick embryo small intestine with experimentally-induced atresia on day 12 and on
      day 16. Changes in enteroendocrine population were examined in gut specimens
      (excised proximal and distal to the atresia) from experimental embryos 19 days
      old and in control sham-operated chick embryos at the same age. Sections from
      proximal and distal bowel and control bowel were stained with Grimelius silver
      stain, a valuable histochemical method for detecting the argyrophil and
      argentophilic cells, and with an immunohistochemical procedure for detecting
      serotonin and neurotensin immunoreactive cells. In chick embryo proximal bowel,
      intestinal dilation differed in the various embryos. We found significantly
      higher enteroendocrine cell counts in proximal bowel than in distal and control
      bowel. The differences depended on the precociousness of surgery and the severity
      of dilation. Considering the major contribution of enteroendocrine cells to the
      peristaltic reflex, our data may help to explain the pathogenesis of motility
      disorders related to intestinal atresia.

PMID- 19864209
TI  - RNA/MBNL1-containing foci in myoblast nuclei from patients affected by myotonic
      dystrophy type 2: an immunocytochemical study.
AB  - Myotonic dystrophy type 2 (DM2) is a dominantly inherited autosomal disease with
      multi-systemic clinical features and it is caused by expansion of a CCTG
      tetranucleotide repeat in the first intron of the zinc finger protein 9 (ZNF9)
      gene in 3q21.The expanded-CCUG-containing transcripts are retained in the cell
      nucleus and accumulate in the form of focal aggregates which specifically
      sequester the muscleblind-like 1 (MBNL1) protein, a RNA binding factor involved
      in the regulation of alternative splicing. The structural organization and
      composition of the foci are still incompletely known. In this study, the nuclear
      foci occurring in cultured myoblasts from DM2 patients were characterised at
      fluorescence and transmission electron microscopy by using a panel of antibodies
      recognizing transcription and processing factors of pre-mRNAs. MBNL1 proved to co
      locate in the nuclear foci with snRNPs and hnRNPs, whereas no co-location was
      observed with RNA polymerase II, the non-RNP splicing factor SC35, the cleavage
      factor CStF and the PML protein. At electron microscopy the MBNL1-containing
      nuclear foci appeared as roundish domains showing a rather homogeneous structure
      and proved to contain snRNPs and hnRNPs. The sequestration of splicing factors
      involved in early phases of pre-mRNA processing supports the hypothesis of a
      general alteration in the maturation of several mRNAs, which could lead to the
      multiple pathological dysfunctions observed in dystrophic patients.

PMID- 19864210
TI  - Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the
      anagen hair follicle in canine species.
AB  - The dermal sheath (DS) of the hair follicle is comprised by fibroblast-like cells
      and extends along the follicular epithelium, from the bulb up to the
      infundibulum. From this structure, cells with stem characteristics were isolated:
      they have a mesenchymal origin and express CD90 protein, a typical marker of
      mesenchymal stem cells. It is not yet really clear in which region of hair
      follicle these cells are located but some experimental evidence suggests that
      dermal stem cells are localized prevalently in the lower part of the anagen hair
      follicle. As there are no data available regarding DS stem cells in dog species,
      we carried out a morphological analysis of the hair follicle DS and performed
      both an immunohistochemical and an immunocytochemical investigation to identify
      CD90+ cells. We immunohistochemically evidenced a clear and abundant positivity
      to CD90 protein in the DS cells located in the lower part of anagen hair
      follicle. The positive cells showed a typical fibroblast-like morphology. They
      were flat and elongated and inserted among bundles of collagen fibres. The whole
      structure formed a close and continuous sleeve around the anagen hair follicle.
      Our immunocytochemical study allowed us to localize CD90 protein at the
      cytoplasmic membrane level.

PMID- 19864211
TI  - Urocortin-like immunoreactivity in the primary lymphoid organs of the duck (Anas
      platyrhynchos).
AB  - Urocortin (UCN) is a 40 aminoacid peptide which belongs to corticotropin
      releasing factor (CRF) family. This family of peptides stimulates the secretion
      of proopiomelanocortin (POMC)-derived peptides, adrenocorticotropic hormone
      (ACTH), beta-endorphin and melanocyte-stimulating hormone (MSH) in the pituitary
      gland. In the present study, using Western blotting and immunohistochemistry, the
      distribution of UCN in the primary lymphoid organs of the duck was investigated
      at different ages. In the cloacal burse and thymus, Western blot demonstrated the
      presence of a peptide having a molecular weight compatible with that of the
      mammalian UCN. In the cloacal burse, immunoreactivity was located in the
      medullary epithelial cells and in the follicular associated and cortico-medullary
      epithelium. In the thymus, immunoreactivity was located in single epithelial
      cells. Double labelling immunofluorescence studies showed that UCN
      immunoreactivity completely colocalised with cytokeratin immunoreactivity in both
      the thymus and cloacal burse. Statistically significant differences in the
      percentage of UCN immunoreactivity were observed between different age periods in
      the cloacal burse. The results suggest that, in birds, urocortin has an important
      role in regulating the function of the immune system.

PMID- 19864212
TI  - Activation of PKC-epsilon counteracts maturation and apoptosis of HL-60 myeloid
      leukemic cells in response to TNF family members.
AB  - Protein kinase C (PKC)-epsilon, a component of the serine/threonine PKC family,
      has been shown to influence the survival and differentiation pathways of normal
      hematopoietic cells. Here, we have modulated the activity of PKC-epsilon with
      specific small molecule activator or inhibitor peptides. PKC-epsilon inhibitor
      and activator peptides showed modest effects on HL-60 maturation when added
      alone, but PKC-epsilon activator peptide significantly counteracted the pro
      maturative activity of tumor necrosis factor (TNF)-alpha towards the
      monocytic/macrophagic lineage, as evaluated in terms of CD14 surface expression
      and morphological analyses. Moreover, while PKC-epsilon inhibitor peptide showed
      a reproducible increase of TNF-related apoptosis inducing ligand (TRAIL)-induced
      apoptosis, PKC-epsilon activator peptide potently counteracted the pro-apoptotic
      activity of TRAIL. Taken together, the anti-maturative and anti-apoptotic
      activities of PKC-epsilon envision a potentially important proleukemic role of
      this PKC family member.

PMID- 19864213
TI  - Niemann-Pick disease, type B with TRAP-positive storage cells and secondary sea
      blue histiocytosis.
AB  - We present 2 cases of Niemann Pick disease, type B with secondary sea-blue
      histiocytosis. Strikingly, in both cases the Pick cells were positive for
      tartrate resistant acid phosphatase, a finding hitherto described only in Gaucher
      cells. This report highlights the importance of this finding as a potential
      cytochemical diagnostic pitfall in the diagnosis of Niemann Pick disease.

PMID- 19864214
TI  - A cautionary tale for risk assessment.

PMID- 19864215
TI  - Response to editorial on "risk of recreational water use in southern California".

PMID- 19864216
TI  - Components of particulate air pollution and emergency department visits in Chile.
AB  - The objective of the present study was to determine the association between
      several elements of particulates and Emergency Department (ED) visits in a
      general population sample. Daily time-series analyses tested the association
      between daily ED visit and air pollutants and components of particulates measured
      in Santiago Centro, a municipality, which includes downtown Santiago during the
      period from 2001 to 2006. The strongest individual effect was seen for elemental
      carbon. A 4.76 microg/m3 increase was associated with a relative risk (RR) of
      1.12 (95% confidence interval [CI] = 1.10-1.14) increase in total ED visits, and
      a RR of 1.18 (95% CI = 1.16-1.21) for respiratory ED visit. Using factor
      analysis, the authors determined that traffic combustion-related particulates
      were significantly associated with ED visits. Among all the sources identified,
      traffic combustion-related particulates had the strongest association with ED
      visits. A factor indicating soil-sourced particles had a weaker but statistically
      significant observed morbidity effect. Of the many components of particulate air
      pollution, those from motor vehicle exhaust had the greatest observed effect on
      morbidity.

PMID- 19864217
TI  - Exposure to air pollution: an intake fraction application in Turin province.
AB  - An application of the intake fraction methodology was carried out in the
      southwestern area of the city of Turin, Italy, one of Europe's more polluted
      areas. The results from the case study were compared to similar analysis
      published in the literature and the intake Fraction (iF) formulation was
      critically revised and evaluated. These findings imply that there is potential
      for improving the evaluation of exposure to transport-related air pollution based
      on the use of the iF.

PMID- 19864218
TI  - Indian medicinal herb: a source of lead and cadmium for humans and animals.
AB  - The authors aimed to analyze 35 commonly used medicinal plants in India by
      exploring the possibilities of translocation of lead and cadmium into humans and
      animals. They collected plant materials from the same sources used by traditional
      healers and commercial drug manufacturers and estimated lead and cadmium levels
      in leaf stem bark, roots, and seeds, depending on the medicinal value of the
      plant portion. The authors determined lead and cadmium content of the digested
      samples using an atomic absorption spectrophotometer. Lead and cadmium
      concentrations were higher in aerial parts of the medicinal plants than in the
      roots. Lead concentration in 54.29% of medicinal plants and cadmium concentration
      in 77.14% of medicinal plants exceeded the maximum permissible level designated
      by the World Health Organization. The results indicate that prolonged consumption
      of such medicinal plants may be detrimental to one's health.

PMID- 19864220
TI  - Temperature enhanced effects of ozone on cardiovascular mortality in 95 large US
      communities, 1987-2000: Assessment using the NMMAPS data.
AB  - A few studies examined interactive effects between air pollution and temperature
      on health outcomes. In this study, the authors aimed to examine whether
      temperature modified effects of ozone on cardiovascular mortality in 95 large US
      cities. The authors separately used a nonparametric regression model and a
      parametric regression model to explore interactive effects of temperature and
      ozone on cardiovascular mortality between May and October of the years from 1987
      to 2000. The authors used a Bayesian meta-analysis to pool estimates. The
      nonparametric and parametric regression models both showed that temperature
      enhanced effects of ozone on mortality, but the effect modification varied across
      regions. A 10-ppb increment in average ozone concentration at 3 previous days was
      associated with 0.41% (95% posterior interval [PI]: -0.19%, 0.93%), 0.27% (95%
      PI: -0.44%, 0.87%), and 1.68% (95% PI: 0.07%, 3.26%) increases in daily
      cardiovascular mortality corresponding to low, moderate, and high levels of
      temperature in all 95 US cities, respectively. The authors concluded that
      temperature modified effects of ozone, particularly in the northern regions.

PMID- 19864219
TI  - Interaction of ambient air pollution with asthma medication on exhaled nitric
      oxide among asthmatics.
AB  - The interaction between ambient air pollution and asthma medication remains
      unclear. The authors compared airway inflammation response to air pollution among
      asthmatics. Increases of 10 ppb of nitrogen dioxide (NO2) and of 10 microg/m3 of
      particulate matter < 10 micron in diameter (PM10) daily concentrations were
      associated with an increase in exhaled nitric oxide (eNO) of 0.13 ppb (95%
      confidence interval = 0.06, 0.19) and of 0.07 ppb (95% confidence interval =
      0.02, 0.12), respectively, in models adjusted for important covariates. The
      results show that the medication could not counteract airway inflammation effects
      of air pollution. Specifically, the patients on triamcinolone decreased the
      sensitivity to PM10 but increased the sensitivity to NO2. The patients on
      salmeterol were more vulnerable to both NO2 and PM10. This study indicates that
      the current pollution levels may still enhance airway inflammation among patients
      with persistent asthma even when they are on asthma medications.

PMID- 19864221
TI  - Occupational insecticide exposure and perception of safety measures among cacao
      farmers in southwestern Nigeria.
AB  - The authors assessed occupational exposure hazards among cacao farmers in
      Southwestern Nigeria. They administered structured questionnaires, supplemented
      with oral interviews, to 150 farmers to obtain information on insecticide use and
      perception of safety measures. The farmers used lindane, diazinon, endosulfan,
      and propoxur for cacao mirid control. Factors promoting exposure included eating
      and drinking during spraying operations, failure to use protective clothing,
      improper storage and disposal of insecticides. Varying proportions of the farmers
      experienced common symptoms associated with exposure hazards. Few presented for
      medical treatment with complaints of frequent fever, strained breathing,
      sleeplessness, loss of memory, etc., symptoms which are suggestive of chronic
      pesticide poisoning. The authors concluded that biological monitoring of the
      effects of insecticides on the health of the farmers is urgently needed together
      with awareness campaign and training on pesticide safety measures.

PMID- 19864222
TI  - Atypical work hours and metabolic syndrome among police officers.
AB  - This study examined whether atypical work hours are associated with metabolic
      syndrome among a random sample of 98 police officers. Shift work and overtime
      data from daily payroll records and reported sleep duration were obtained.
      Metabolic syndrome was defined as elevated waist circumference and triglycerides,
      low HDL cholesterol, hypertension, and glucose intolerance. Multivariate analysis
      of variance and analysis of covariance models were used for analyses. Officers
      working midnight shifts were on average younger and had a slightly higher mean
      number of metabolic syndrome components. Stratification on sleep duration and
      overtime revealed significant associations between midnight shifts and the mean
      number of metabolic syndrome components among officers with less sleep (p = .013)
      and more overtime (p = .007). Results suggest shorter sleep duration and more
      overtime combined with midnight shift work may be important contributors to the
      metabolic syndrome.

PMID- 19864223
TI  - Diurnal temperature range and daily cardiovascular mortalities among the elderly
      in Hong Kong.
AB  - The authors aimed to examine the association between diurnal temperature range
      (DTR) and daily mortalities due to cardiovascular disease among people aged 65
      years and older in Hong Kong, China. The authors used a generalized additive
      model to regress daily mortalities of the elderly due to cardiovascular disease
      on DTR and daily concentrations of air pollutants from 1997 to 2002. They also
      tested the effects of different lag days of DTR on mortality. Results indicate
      significant associations between cardiovascular mortality and DTR at lag day 1
      and at lag days 0-1 to 0-5. The largest effect was at lag days 0-3 (relative
      risks = 1.017; 95% confidence interval = 1.003-1.031). The authors recommend that
      special attention be paid to the elderly population to protect them from
      excessive diurnal variations in temperature.

PMID- 19864224
TI  - Surgical applications of methyl methacrylate: a review of toxicity.
AB  - Methyl methacrylate (MMA) is a monomer of acrylic resin widely used in a variety
      of medical, dental, and industrial applications. Its extensive use in surgery,
      particularly for arthroplasties, has often raised concerns regarding potential
      human toxicity for orthopaedic surgeons, surgical nurses, and other operating
      room staff who are occupationally exposed to the compound. The main toxic effects
      of MMA exposure appear to involve the cardiovascular system. When exposed to MMA
      in the work environment, surgical staff have been reported to suffer from
      hypersensitivity, asthmatic reactions, local neurological symptoms, irritations
      and local dermatological reactions. The integrity of latex gloves may also be
      compromised following exposure to MMA during surgical procedures. At present, MMA
      is not thought to be carcinogenic to humans under normal conditions of use.
      Nevertheless, sound occupational hygiene practices should still be used to help
      reduce workplace exposure to MMA during orthopaedic and other medical procedures.
      Surgical staff should avoid direct contact with MMA mixtures wherever possible,
      and room ventilation and adequate airflow should also be optimized. In the
      present article, the authors review studies relating to MMA toxicity in surgical
      practice, updating in part a previous literature review and expanding on the
      toxicity of MMA within the surgical setting.

PMID- 19864225
TI  - Advice to a student interested in "medical geology".

PMID- 19864226
TI  - Re: Impact of reporting gram stain results from blood cultures on the selection
      of antimicrobial agents.

PMID- 19864227
TI  - Refining diagnostic criteria for high-grade dysplasia in Barrett esophagus.

PMID- 19864228
TI  - Recommendations for the reporting of surgically resected thymic epithelial
      tumors.

PMID- 19864229
TI  - Impact of reporting gram stain results from blood culture bottles on the
      selection of antimicrobial agents.
AB  - We assessed the usefulness of reporting direct blood Gram stain results compared
      with the results of positive blood cultures in 482 episodes and monitored impact
      on selection of antimicrobial treatment. We found that the reporting groups
      "Staphylococcus spp," "Pseudomonas spp and related organisms," and "yeasts"
      identified in this way matched perfectly with later culture identification. When
      the report indicated Staphylococcus spp or Pseudomonas spp and related organisms,
      physicians started or changed antimicrobials suitable for these bacteria more
      frequently than when "other streptococci" and "family Enterobacteriaceae" were
      reported (P < .05). Incorrect recognition of Acinetobacter spp as
      Enterobacteriaceae family is still the most challenging problem in this context.
      Gram stain results that definitively identify Staphylococcus spp, Pseudomonas spp
      and related organisms, and yeasts reliably can be rapidly provided by clinical
      laboratories; this information has a significant impact on early selection of
      effective antimicrobials. Further investigation is needed to assess the clinical
      impact of reporting Gram stain results in bacteremia.

PMID- 19864230
TI  - Analysis of human T-cell lymphotropic virus in CD25+ anaplastic large cell
      lymphoma in children.
AB  - Anaplastic large cell lymphoma (ALCL) is recognized as 2 distinct diseases:
      anaplastic lymphoma kinase (ALK)+ ALCL and ALK- ALCL. ALK+ ALCL occurs in younger
      patients and has a better prognosis. Human T-cell lymphotropic virus (HTLV-1) is
      linked to the development of adult T-cell leukemia/lymphoma (ATLL), which
      frequently expresses CD25. CD25 is significantly expressed in childhood ALCL. In
      Brazil, HTLV-1 infection is endemic, and vertical transmission is responsible for
      spread to children. Of HTLV-1 carriers, 90% or more remain asymptomatic. Some
      cases of adult HTLV-1-related lymphomas have characteristics of ALCL but are
      considered CD30+ ATLL subtypes. No similar cases have been described in children.
      We analyzed 33 cases of pediatric ALCL, CD25+ and CD25-, for proviral HTLV-1 DNA.
      All cases corresponded to the common histologic ALCL type and were CD30+ in
      virtually all neoplastic cells. ALK expression was observed in 31 (94%) of 33
      cases; CD25 was positive in 27 (82%), including 1 ALK- ALCL case. There was a
      strong positive correlation between ALK and CD25 expression. None of the cases
      showed proviral HTLV-1 DNA. ALCL in children has no relationship with HTLV-1; the
      frequent CD25 expression must be explained by a mechanism different from that in
      ATLL.

PMID- 19864231
TI  - The range of hemoglobin A(2) in hemoglobin E heterozygotes as determined by
      capillary electrophoresis.
AB  - Capillary electrophoresis (CE) is capable of distinguishing hemoglobin E (HbE)
      from hemoglobin A(2) (HbA(2)), thus permitting quantification of HbA(2) in
      patients with HbE. In this study, routine samples submitted for evaluation of
      hemoglobinopathy that demonstrated HbE were studied by high-pressure liquid
      chromatography and CE. The data for 52 samples from adult HbE heterozygotes were
      compared with those for a control group consisting of 209 patients. The mean
      HbA(2) of patients with HbE trait was 3.4% (SD, 0.4%), which was significantly
      higher (P < .001) than the 2.6% (SD, 0.4%) for the control group. Seven samples
      from adults homozygous for HbE were also evaluated. The mean HbA(2) of HbE
      homozygotes was 4.4%, which was significantly greater (P < .001) than the HbA(2)
      values for the HbE heterozygotes. Data from these cases provide an estimate of
      the range of HbA(2) in patients with HbE when evaluated by CE.

PMID- 19864233
TI  - Aberrant expression of cyclin a correlates with morphogenesis of reed-sternberg
      cells in Hodgkin lymphoma.
AB  - Reed-Sternberg (RS) cells represent a histopathologic hallmark for Hodgkin
      lymphoma (HL). Viral proteins may induce aberrant expression of cyclin A and lead
      to multinucleation in virus-infected cells. We investigated whether Epstein-Barr
      virus (EBV) latent membrane protein-1 (LMP1) and cyclin A are involved in the
      morphogenesis of RS cells. We immunohistochemically analyzed "individual" tumor
      cells in 34 HLs for the subcellular expression of cyclin A and HL-related
      markers. In LMP1+ and LMP1- HLs, multinucleated RS cells aberrantly expressed
      cyclin A in cytoplasm, while the mononuclear Hodgkin cells expressed cyclin A
      predominantly in nuclei (P < .001). No differential expression of CD15, CD30, or
      CD99 in HL cells was found. In vitro, EBV-LMP1 increased cytoplasmic cyclin A
      expression and multinucleation in an HL cell line. Therefore, the aberrant
      expression of cyclin A is commonly associated with RS cell morphologic features
      in HL, probably through LMP1 signaling or other similar mechanisms in EBV- cases.

PMID- 19864232
TI  - Immunoarchitectural patterns in nodal marginal zone B-cell lymphoma: a study of
      51 cases.
AB  - Nodal marginal zone lymphoma (NMZL) represents a rare and heterogeneous group
      that lacks markers specific for the diagnosis. We evaluated morphologic and
      immunoarchitectural features of 51 NMZLs, and the following immunostains were
      performed: CD20, CD21, CD23, CD5, CD3, CD43, CD10, Ki-67, BCL1, BCL2, BCL6, HGAL,
      and LMO2. Four immunoarchitectural patterns were evident: diffuse (38 [75%]),
      well-formed nodular/follicular (5 [10%]), interfollicular (7 [14%]), and
      perifollicular (1 [2%]). Additional features included a monocytoid component (36
      [71%]), admixed large cells (20 [39%]), plasma cells (24 [47%]),
      compartmentalizing stromal sclerosis (13 [25%]), and prominent blood vessel
      sclerosis (10 [20%]). CD21 highlighted disrupted follicular dendritic cell
      meshwork in 35 (71%) of 49 cases, and CD43 coexpression was present in 10 (24%)
      of 42 cases. A panel of germinal center-associated markers was helpful in
      eliminating cases of diffuse follicle center lymphoma. Our results highlight the
      histologic and immunoarchitectural spectrum of NMZL and the usefulness of
      immunohistochemical analysis for CD43, CD23, CD21, BCL6, HGAL, and LMO2 in the
      diagnosis of NMZL.

PMID- 19864234
TI  - Utility of CD56 immunohistochemical studies in follow-up of plasma cell myeloma.
AB  - Although 70% to 80% of plasma cell myelomas (PCMs) express CD56, few data are
      available on the usefulness of CD56 immunohistochemical analysis in assessing
      residual disease. We retrospectively reviewed 127 PCM posttreatment bone marrow
      (BM) specimens, classifying them as positive or negative for residual disease
      (independent of CD56 immunohistochemical studies) based on abnormal plasma cell
      (PC) morphologic features or flow cytometry (FC) and/or light chain restriction
      by immunohistochemical studies (conventional criteria). CD56 immunohistochemical
      analysis was performed on these and 20 negative lymphoma staging BM specimens. Of
      127 BM specimens, 74 were positive and 53 were negative for residual PCM by
      conventional criteria. Of 74 BM specimens positive by conventional criteria, 59
      (80%) demonstrated CD56 (strong+) PCs in clusters and/or with cytologic atypia.
      Of the 53 BM specimens negative by conventional criteria, 3 showed CD56 (strong+)
      morphologically atypical PCs in clusters or scattered. CD56 immunohistochemical
      analysis is useful for detecting residual PCM, particularly in morphologically
      equivocal cases in which light chain restriction cannot be demonstrated, and may
      serve as a potential response criterion.

PMID- 19864235
TI  - Composite pheochromocytoma: a clinicopathologic and molecular comparison with
      ordinary pheochromocytoma and neuroblastoma.
AB  - Composite pheochromocytoma is a rare adrenal tumor composed of ordinary
      pheochromocytoma and other components, most frequently neuroblastic elements.
      Little is known about its biologic potential, therefore creating a clinical
      dilemma on diagnosis. This study investigates the clinical characteristics and N
      myc amplification status of 4 cases of composite pheochromocytoma and compares
      them with selected cases of ordinary pheochromocytoma and neuroblastoma. The age
      range of the patients with composite pheochromocytoma was 15 to 40 years with an
      equal M/F ratio, including 2 patients with syndromes. None of these composite
      pheochromocytomas demonstrated N-myc amplification, none recurred, and there were
      no deaths. Of the classic pheochromocytomas, none demonstrated N-myc
      amplification, 2 recurred, and there were no deaths. Of the neuroblastomas, 5
      (50%) of 10 showed significant N-myc amplification, and there were 4 known
      recurrences and 5 known deaths. These findings suggest that composite
      pheochromocytoma may be regarded as a histologic variant of classic
      pheochromocytoma.

PMID- 19864236
TI  - Justification of the change from 10% to 30% for the immunohistochemical HER2
      Scoring criterion in breast cancer.
AB  - We compared the American Society of Clinical Oncology/College of American
      Pathologists (ASCO/CAP) immunohistochemical scoring criterion (30%) for
      determining HER2 status and the Food and Drug Administration criterion (10%) with
      fluorescence in situ hybridization (FISH), the HER2 gene amplification method in
      328 cases of breast cancer. Of 294 tumor samples successfully analyzed
      simultaneously by FISH and immunohistochemically, 178 of 196 cases scored 3+
      using the 10% and the 30% criteria. Using FISH as the reference, the number of
      false-positives was reduced from 24 to 9 after application of the 30% criterion.
      The specificity of immunohistochemical analysis was higher with the 30% (92.0%)
      vs the 10% (78.8%) criterion. The kappa coefficient between FISH and
      immunohistochemical analysis was increased to 0.850 (almost perfect agreement; P
      < .001) after application of the 30% criterion vs 0.757 (substantial agreement)
      for the 10% criterion; the false-positive rate decreased to 5.1% from 12.2%. The
      chi(2) test showed that immunohistochemical analysis had significantly higher
      accuracy with the 30% (94.9%) vs the 10% (87.8%; P = .014) criterion. Our results
      from a large series of Chinese patients with breast cancer support that the
      ASCO/CAP 30% criterion may offer better results for assessing HER2 status.

PMID- 19864237
TI  - Expression of hepatocyte antigen in small intestinal epithelium and
      adenocarcinoma.
AB  - Hepatocyte antigen is recognized by antibody Hep Par 1, a widely used diagnostic
      immunomarker for hepatocellular carcinoma and tumors with hepatoid
      differentiation. Hepatocyte antigen expression has also been detected in
      nonneoplastic small intestinal epithelium, but expression in small intestinal
      adenocarcinoma has not been well investigated. We immunohistochemically examined
      39 nonampullary small intestinal adenocarcinomas for hepatocyte antigen
      expression; 34 cases contained normal-appearing nonneoplastic small intestinal
      mucosa on the same tissue sections. In 30 cases (88%), the nonneoplastic mucosa
      exhibited granular cytoplasmic Hep Par 1 staining exclusively in the epithelium.
      Only 9 small intestinal adenocarcinomas (23%) showed focal positive cytoplasmic
      staining. Nonneoplastic colonic epithelium was negative for Hep Par 1. In 31
      colorectal adenocarcinomas, 3 (10%) showed positive staining for Hep Par 1 (1
      diffuse, 2 focal), a frequency not different from that for small intestinal
      adenocarcinomas (P = .2467). Tumors expressing hepatocyte antigen did not exhibit
      evidence of hepatoid differentiation and were histologically indistinguishable
      from hepatocyte antigen-negative tumors. Hepatocyte antigen immunoreactivity is
      selectively expressed in nonneoplastic small intestinal enterocytes but not in
      colonocytes, suggesting a potential physiologic role in intestinal biology.
      Whether the loss of antigen expression in a large number of small intestinal
      adenocarcinomas serves a role in small intestinal tumorigenesis remains to be
      investigated.

PMID- 19864238
TI  - Acute fungal sinusitis: natural history and the role of frozen section.
AB  - Acute fungal sinusitis is a life-threatening infection affecting
      immunocompromised patients. Historically, the most commonly recovered fungi are
      Aspergillus and Mucor. The extent of potentially disfiguring debridement surgery
      is grossly determined by the appearance of bleeding at the margins, signifying
      viable tissue and the absence of fungus. Requests for frozen section may concern
      the initial diagnosis and the intraoperative verification of margin status. In 12
      patients with acute fungal sinusitis, frozen section was used in 8. Routine H&E
      stains demonstrated fungal hyphae in necrotic debris in 5 cases, often associated
      with vascular and perineural invasion. All patients underwent extensive sinus
      debridement, including orbital exenteration in 2 cases. All 12 patients died, 9
      of fungal sepsis. Autopsy in 3 patients showed pulmonary involvement (2 cases),
      intracranial spread (1 case), and no residual fungus (1 case). Inexperience with
      organism recognition is surmountable. Frozen section has a role in the management
      of this devastating disease.

PMID- 19864239
TI  - A histologically defined subset of high-grade dysplasia in Barrett mucosa is
      predictive of associated carcinoma.
AB  - To ascertain the prevalence of carcinoma in esophagi resected for high-grade
      dysplasia (HGD) using current criteria and to evaluate histologic features that
      may predict concurrent carcinoma, we studied specimens from 127 esophagectomies
      performed for HGD, or HGD "suspicious" for carcinoma (HGD/S) in Barrett mucosa.
      Corresponding biopsy specimens in 69 cases were reviewed and reclassified. Based
      on original diagnoses, carcinoma was present in 15 (17%) of 89 HGD and 28 (74%)
      of 38 HGD/S cases. By reclassification, only 1 (5%) of 21 cases with HGD had
      carcinoma in the resection specimen. Of 25 cases reclassified as HGD/S, 18 (72%)
      had carcinoma in the resection specimen, as did 17 (74%) of 23 reclassified as
      adenocarcinoma. With 1 additional select histologic feature, the risk of
      carcinoma was 39%; with 2 or more features, the risk increased to 83% to 88%.
      Based on current criteria, no more than 5% of esophagectomies performed for a
      biopsy diagnosis of Barrett HGD harbor carcinoma. When HGD/S is diagnosed based
      on certain additional features, carcinoma is found in nearly 40% of cases with 1
      feature and more than 80% with 2 or more features. Our findings highlight the
      evolution of diagnostic criteria for Barrett dysplasia.

PMID- 19864240
TI  - An updated approach to the diagnosis of myeloid leukemia cutis.
AB  - The diagnosis of myeloid leukemia cutis can be difficult, particularly in the
      context of an initial skin biopsy with a malignant hematopoietic neoplasm. We
      studied the immunohistochemical characteristics of 33 cases of myeloid leukemia
      cutis diagnosed at Stanford University Medical Center, Stanford, CA, 1996-2007,
      and compared them with the corresponding bone marrow blast immunophenotype and
      World Health Organization classification (2008). In the skin, CD43 marked 97% of
      cases (32/33), myeloperoxidase marked 42% (14/33), CD68 marked 94% (31/33), CD163
      marked 25% (7/28), and CD56 marked 47% (14/30). CD34 and CD117 were predominantly
      negative. In 19 cases in which myeloperoxidase was negative, all marked with CD68
      and CD43. The flow cytometric immunophenotype of the leukemic blasts in the bone
      marrow was discordant with the immunohistochemical profile in the skin in all
      cases, showing loss or gain of at least 1 antigen. Given the immunophenotypic
      differences between skin and bone marrow blasts, we provide an updated
      immunohistochemical approach to the diagnosis of myeloid leukemia cutis.

PMID- 19864241
TI  - FU-MK-1 expression in human gallbladder carcinoma: an antigenic prediction marker
      for a better postsurgical prognosis.
AB  - Gallbladder carcinoma is an aggressive type of neoplasm difficult to cure by
      conventional procedures. Because of the lack of reliable markers for assessing
      the prognosis, this retrospective study was designed to investigate the
      prognostic significance of MK-1 overexpression in human carcinoma of the
      gallbladder. Immunohistochemical staining using monoclonal antibody FU-MK-1 (MK-1
      antigen) was performed on paraffin-embedded tissues from 63 patients who had
      undergone surgical resection for gallbladder carcinoma. Expression of MK-1 was
      found in 50 (79%) of 63 tumor samples. All 21 papillary and 12 of 13 well
      differentiated tubular adenocarcinomas but only 1 of 8 poorly differentiated
      adenocarcinomas were positive for FU-MK-1. Multivariate analysis showed that only
      MK-1 expression was an independent prognostic marker (P = .0473), and Kaplan
      Meier curves showed that MK-1 expression was significantly related to increased
      overall survival (P < .0001). These results suggest that MK-1 expression is a
      prognostic marker in gallbladder carcinoma.

PMID- 19864242
TI  - Repeated molecular testing in gliomas: a retrospective study of 53 cases.
AB  - The value of repeated molecular testing in patients with multiple resections of
      gliomas is unclear. The purpose of this study was to assess for evidence of
      molecular changes for chromosome 1p/19q deletions and epidermal growth factor
      receptor (EGFR) amplification by fluorescence in situ hybridization in 53 glioma
      cases in which repeated testing was done. Paired results for 1p evaluation
      demonstrated a change in the profile from intact to loss in 1 (2%) of 50 cases;
      19q evaluation demonstrated a change in profile in 4 (10%) of 41 cases. There was
      no change in the EGFR expression in any of the cases tested. There was no change
      in the clinical management based on the repeated molecular tests in patients with
      discrepant repeated results. Hence, there seems to be no indication for reflex
      repeated 1p/19q or EGFR testing in gliomas at the time of repeated biopsy or
      resection.

PMID- 19864243
TI  - The reproducibility of CIN diagnoses among different pathologists: data from
      histology reviews from a multicenter randomized study.
AB  - The reproducibility of cervical histology diagnoses is critical for efficient
      screening and to evaluate the effectiveness of new technologies. The vast
      majority of cervical intraepithelial neoplasia (CIN) diagnoses reported in the
      New Technologies for Cervical Cancer study were blindly reviewed by 2 independent
      pathologists. Only H&E-stained slides were used for the review. The reviewers
      were asked to reclassify cases using the following categories: normal CIN 1, CIN
      2, CIN 3, and squamous and glandular invasive cancer. We reviewed 1,003 cases.
      The interobserver agreement was 0.36 (95% confidence interval [CI], 0.32-0.40)
      with an unweighted kappa and 0.54 with a weighted kappa (95% CI, 0.50-0.58). The
      kappa values from dichotomous classifications with the threshold at CIN 2 were
      0.69 (95% CI, 0.64-0.73) and 0.57 (95% CI, 0.51-0.63) with the threshold at CIN
      3. The CIN 2 diagnosis had the lowest class-specific agreement, with fewer than
      50% of cases confirmed by the panel members, which supports the fact that CIN 2
      is not a well-defined stage in the pathogenesis of cervical neoplasia.

PMID- 19864244
TI  - Automated cellular imaging system III for assessing HER2 status in breast cancer
      specimens: development of a standardized scoring method that correlates with
      FISH.
AB  - The goal of this study was to assess the performance characteristics of the
      Automated Cellular Imaging System (ACIS III) for HER2 immunohistochemical
      analysis. The study was performed on 187 biopsy slides from patients who
      underwent HER2 testing between January and February 2008. Three scoring methods
      by the ACIS III were compared with the manual score and fluorescence in situ
      hybridization (FISH) results for HER2 amplification. The equal distribution score
      (EQD) method, in which 2 areas each of high-, moderate-, and low-intensity
      staining were measured, most closely matched the FISH HER2 amplification result.
      The numbers of immunohistochemically negative (0 or 1+)/FISH+ cases were
      equivalent for all methods. The EQD method had significantly fewer 2+ cases (n =
      16) (P < .001) vs the manual method (n = 35) and yielded a higher positive
      predictive value (38%) for HER2 amplification compared with the manual method
      (20%). The EQD method may more accurately identify FISH-amplified HER2 cases with
      fewer 2+ cases that would be "reflexed" to FISH compared with the manual method.

PMID- 19864245
TI  - Decorin is significantly overexpressed in nephrogenic systemic fibrosis.
AB  - The role of the proteoglycans in the pathogenesis of nephrogenic systemic
      fibrosis (NSF) is unclear. We assessed expression of decorin, versican, and
      transforming growth factor beta1 (TGF-beta1) in skin specimens of 10 patients
      with biopsy-proven NSF and different control groups. Real-time reverse
      transcription-polymerase chain reaction studies and immunohistochemical analysis
      were performed on full-thickness skin specimens. The messenger RNA (mRNA) and
      protein levels of decorin were significantly higher in the skin lesions of
      patients with NSF than in skin lesions of patients with systemic sclerosis,
      patients undergoing hemodialysis, and healthy subjects. The versican mRNA levels
      in NSF lesions differed significantly only from the levels in healthy subjects.
      TGF-beta1 mRNA expression was significantly overexpressed in NSF lesions compared
      with control skin specimens investigated. In NSF specimens, the mRNA expression
      of TGF-beta1 and decorin were highly correlated (r = 0.92). Our results suggest
      that decorin and TGF-beta1 may have a fundamental role in the pathogenesis of
      NSF. Conversely, versican seems less likely to be of pathogenetic significance in
      NSF.

PMID- 19864246
TI  - In Memoriam: Sean Breanndan Moore (1944-2009).

PMID- 19864247
TI  - Reporting confidence intervals for myelodysplasia blast counts.

PMID- 19864249
TI  - High content screening for inhibitors of protein interactions and post
      translational modifications in primary cells by proximity ligation.
AB  - The cost of developing new drugs is a major obstacle for pharmaceutical companies
      and academia with many drugs identified in the drug discovery process failing
      approval for clinical use due to lack of intended effect or because of severe
      side effects. Since the early 1990 s, high throughput screening of drug compounds
      has increased enormously in capacity but has not resulted in a higher success
      rate of the identified drugs. Thus, there is a need for methods that can identify
      biologically relevant compounds and more accurately predict in vivo effects early
      in the drug discovery process. To address this, we developed a proximity ligation
      based assay for high content screening of drug effects on signaling pathways. As
      a proof of concept, we used the assay to screen through a library of previously
      identified kinase inhibitors, including six clinically used tyrosine kinase
      inhibitors, to identify compounds that inhibited the platelet-derived growth
      factor (PDGF) receptor beta signaling pathway in stimulated primary human
      fibroblasts. Thirteen of the 80 compounds were identified as hits, and the dose
      responses of these compounds were measured. The assay exhibited a very high Z'
      factor (0.71) and signal to noise ratio (11.7), demonstrating excellent ability
      to identify compounds interfering with the specific signaling event. A comparison
      with regular immunofluorescence detection of phosphorylated PDGF receptor
      demonstrated a far superior ability by the in situ proximity ligation assay to
      reveal inhibition of receptor phosphorylation. In addition, inhibitor-induced
      perturbation of protein-protein interactions of the PDGF signaling pathway could
      be quantified, further demonstrating the usefulness of the assay in drug
      discovery.

PMID- 19864250
TI  - Bioinformatics approaches for genomics and post genomics applications of next
      generation sequencing.
AB  - Technical advances such as the development of molecular cloning, Sanger
      sequencing, PCR and oligonucleotide microarrays are key to our current capacity
      to sequence, annotate and study complete organismal genomes. Recent years have
      seen the development of a variety of so-called 'next-generation' sequencing
      platforms, with several others anticipated to become available shortly. The
      previously unimaginable scale and economy of these methods, coupled with their
      enthusiastic uptake by the scientific community and the potential for further
      improvements in accuracy and read length, suggest that these technologies are
      destined to make a huge and ongoing impact upon genomic and post-genomic biology.
      However, like the analysis of microarray data and the assembly and annotation of
      complete genome sequences from conventional sequencing data, the management and
      analysis of next-generation sequencing data requires (and indeed has already
      driven) the development of informatics tools able to assemble, map, and interpret
      huge quantities of relatively or extremely short nucleotide sequence data. Here
      we provide a broad overview of bioinformatics approaches that have been
      introduced for several genomics and functional genomics applications of next
      generation sequencing.

PMID- 19864251
TI  - Preferential access to genetic information from endogenous hominin ancient DNA
      and accurate quantitative SNP-typing via SPEX.
AB  - The analysis of targeted genetic loci from ancient, forensic and clinical samples
      is usually built upon polymerase chain reaction (PCR)-generated sequence data.
      However, many studies have shown that PCR amplification from poor-quality DNA
      templates can create sequence artefacts at significant levels. With hominin
      (human and other hominid) samples, the pervasive presence of highly PCR
      amplifiable human DNA contaminants in the vast majority of samples can lead to
      the creation of recombinant hybrids and other non-authentic artefacts. The
      resulting PCR-generated sequences can then be difficult, if not impossible, to
      authenticate. In contrast, single primer extension (SPEX)-based approaches can
      genotype single nucleotide polymorphisms from ancient fragments of DNA as
      accurately as modern DNA. A single SPEX-type assay can amplify just one of the
      duplex DNA strands at target loci and generate a multi-fold depth-of-coverage,
      with non-authentic recombinant hybrids reduced to undetectable levels. Crucially,
      SPEX-type approaches can preferentially access genetic information from damaged
      and degraded endogenous ancient DNA templates over modern human DNA contaminants.
      The development of SPEX-type assays offers the potential for highly accurate,
      quantitative genotyping from ancient hominin samples.

PMID- 19864252
TI  - The Mouse Genome Database: enhancements and updates.
AB  - The Mouse Genome Database (MGD) is a major component of the Mouse Genome
      Informatics (MGI, http://www.informatics.jax.org/) database resource and serves
      as the primary community model organism database for the laboratory mouse. MGD is
      the authoritative source for mouse gene, allele and strain nomenclature and for
      phenotype and functional annotations of mouse genes. MGD contains comprehensive
      data and information related to mouse genes and their functions, standardized
      descriptions of mouse phenotypes, extensive integration of DNA and protein
      sequence data, normalized representation of genome and genome variant information
      including comparative data on mammalian genes. Data for MGD are obtained from
      diverse sources including manual curation of the biomedical literature and direct
      contributions from individual investigator's laboratories and major informatics
      resource centers, such as Ensembl, UniProt and NCBI. MGD collaborates with the
      bioinformatics community on the development and use of biomedical ontologies such
      as the Gene Ontology and the Mammalian Phenotype Ontology. Recent improvements in
      MGD described here includes integration of mouse gene trap allele and sequence
      data, integration of gene targeting information from the International Knockout
      Mouse Consortium, deployment of an MGI Biomart, and enhancements to our batch
      query capability for customized data access and retrieval.

PMID- 19864254
TI  - The integrated microbial genomes system: an expanding comparative analysis
      resource.
AB  - The integrated microbial genomes (IMG) system serves as a community resource for
      comparative analysis of publicly available genomes in a comprehensive integrated
      context. IMG contains both draft and complete microbial genomes integrated with
      other publicly available genomes from all three domains of life, together with a
      large number of plasmids and viruses. IMG provides tools and viewers for
      analyzing and reviewing the annotations of genes and genomes in a comparative
      context. Since its first release in 2005, IMG's data content and analytical
      capabilities have been constantly expanded through regular releases. Several
      companion IMG systems have been set up in order to serve domain specific needs,
      such as expert review of genome annotations. IMG is available at
      http://img.jgi.doe.gov.

PMID- 19864253
TI  - A global view of the nonprotein-coding transcriptome in Plasmodium falciparum.
AB  - Nonprotein-coding RNAs (npcRNAs) represent an important class of regulatory
      molecules that act in many cellular pathways. Here, we describe the experimental
      identification and validation of the small npcRNA transcriptome of the human
      malaria parasite Plasmodium falciparum. We identified 630 novel npcRNA
      candidates. Based on sequence and structural motifs, 43 of them belong to the C/D
      and H/ACA-box subclasses of small nucleolar RNAs (snoRNAs) and small Cajal body
      specific RNAs (scaRNAs). We further observed the exonization of a functional
      H/ACA snoRNA gene, which might contribute to the regulation of ribosomal protein
      L7a gene expression. Some of the small npcRNA candidates are from telomeric and
      subtelomeric repetitive regions, suggesting their potential involvement in
      maintaining telomeric integrity and subtelomeric gene silencing. We also detected
      328 cis-encoded antisense npcRNAs (asRNAs) complementary to P. falciparum protein
      coding genes of a wide range of biochemical pathways, including determinants of
      virulence and pathology. All cis-encoded asRNA genes tested exhibit lifecycle
      specific expression profiles. For all but one of the respective sense-antisense
      pairs, we deduced concordant patterns of expression. Our findings have important
      implications for a better understanding of gene regulatory mechanisms in P.
      falciparum, revealing an extended and sophisticated npcRNA network that may
      control the expression of housekeeping genes and virulence factors.

PMID- 19864255
TI  - Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p
      helicase in RNA surveillance.
AB  - The mechanism of human mitochondrial RNA turnover and surveillance is still a
      matter of debate. We have obtained a cellular model for studying the role of
      hSuv3p helicase in human mitochondria. Expression of a dominant-negative mutant
      of the hSUV3 gene which encodes a protein with no ATPase or helicase activity
      results in perturbations of mtRNA metabolism and enables to study the processing
      and degradation intermediates which otherwise are difficult to detect because of
      their short half-lives. The hSuv3p activity was found to be necessary in the
      regulation of stability of mature, properly formed mRNAs and for removal of the
      noncoding processing intermediates transcribed from both H and L-strands,
      including mirror RNAs which represent antisense RNAs transcribed from the
      opposite DNA strand. Lack of hSuv3p function also resulted in accumulation of
      aberrant RNA species, molecules with extended poly(A) tails and degradation
      intermediates truncated predominantly at their 3'-ends. Moreover, we present data
      indicating that hSuv3p co-purifies with PNPase; this may suggest participation of
      both proteins in mtRNA metabolism.

PMID- 19864256
TI  - Measurement of replication structures at the nanometer scale using super
      resolution light microscopy.
AB  - DNA replication, similar to other cellular processes, occurs within dynamic
      macromolecular structures. Any comprehensive understanding ultimately requires
      quantitative data to establish and test models of genome duplication. We used two
      different super-resolution light microscopy techniques to directly measure and
      compare the size and numbers of replication foci in mammalian cells. This
      analysis showed that replication foci vary in size from 210 nm down to 40 nm.
      Remarkably, spatially modulated illumination (SMI) and 3D-structured illumination
      microscopy (3D-SIM) both showed an average size of 125 nm that was conserved
      throughout S-phase and independent of the labeling method, suggesting a basic
      unit of genome duplication. Interestingly, the improved optical 3D resolution
      identified 3- to 5-fold more distinct replication foci than previously reported.
      These results show that optical nanoscopy techniques enable accurate measurements
      of cellular structures at a level previously achieved only by electron microscopy
      and highlight the possibility of high-throughput, multispectral 3D analyses.

PMID- 19864257
TI  - Involvement of the nuclear cap-binding protein complex in alternative splicing in
      Arabidopsis thaliana.
AB  - The nuclear cap-binding protein complex (CBC) participates in 5' splice site
      selection of introns that are proximal to the mRNA cap. However, it is not known
      whether CBC has a role in alternative splicing. Using an RT-PCR alternative
      splicing panel, we analysed 435 alternative splicing events in Arabidopsis
      thaliana genes, encoding mainly transcription factors, splicing factors and
      stress-related proteins. Splicing profiles were determined in wild type plants,
      the cbp20 and cbp80(abh1) single mutants and the cbp20/80 double mutant. The
      alternative splicing events included alternative 5' and 3' splice site selection,
      exon skipping and intron retention. Significant changes in the ratios of
      alternative splicing isoforms were found in 101 genes. Of these, 41% were common
      to all three CBC mutants and 15% were observed only in the double mutant. The
      cbp80(abh1) and cbp20/80 mutants had many more changes in alternative splicing in
      common than did cbp20 and cbp20/80 suggesting that CBP80 plays a more significant
      role in alternative splicing than CBP20, probably being a platform for
      interactions with other splicing factors. Cap-binding proteins and the CBC are
      therefore directly involved in alternative splicing of some Arabidopsis genes and
      in most cases influenced alternative splicing of the first intron, particularly
      at the 5' splice site.

PMID- 19864258
TI  - Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes.
AB  - Activating Transcription Factor 3 (ATF3), a member of the ATF/CREB family, is
      induced rapidly by various stresses. Its induction mechanism and role in response
      to changes in cellular redox status, however, have not been elucidated. Here, we
      found that NF-E2-related factor 2 (Nrf2), a transcription factor known to bind to
      antioxidant response element (ARE) in promoters, transcriptionally upregulated
      ATF3 expression in astrocytes. Treatment with Nrf2 activators and oxidants
      provoked ATF3 induction in astrocytes, whereas its expression was reduced in Nrf2
      depleted cells. We further demonstrated that the consensus ARE in the ATF3
      promoter is critical for Nrf2-mediation by promoter analyses using an ATF3
      promoter-driven luciferase construct and a chromatin immunoprecipitation assay.
      In addition, we found that Nrf2-dependent ATF3 induction contributed to the
      antioxidative and cytoprotective functions of Nrf2 in astrocytes. Taken together,
      our findings suggest that ATF3 is a new target for Nrf2 and has a cytoprotective
      function in astrocytes.

PMID- 19864259
TI  - Epidemiological criminology: drug use among African American gang members.
AB  - Epidemiological methods and public health theories can be tied to theories of
      crime and delinquency and used to create evidence-based policy. Interdisciplinary
      theoretical approaches to existing, and emerging, public health and criminal
      justice problems hold great promise. Differential association theory postulates
      that close association with delinquent peers leads to an increase in deviant
      activities such as illicit drug use. Social cognitive theory postulates that
      health behavior change is driven by the interaction of (a) cognitive states that
      support a health outcome, (b) the social and contextual environment, (c) and
      individual action. Combined, these theories can be applied to drug eradication
      programs as well as other health and crime issues. Focus groups and interviews
      were performed to identify rates of illicit substance use among incarcerated
      African American adolescent male gang members and nongang members. The policy
      recommendations illustrate the convergence of criminological and epidemiological
      theory under the new paradigm of epidemiological criminology or ''EpiCrim.''

PMID- 19864260
TI  - Transient thermal dissipation method of xylem sap flow measurement: multi-species
      calibration and field evaluation.
AB  - The transient thermal dissipation (TTD) method developed by Do and Rocheteau
      (2002b) is a close evolution of the original constant thermal dissipation (CTD)
      method of Granier (1985). The TTD method has the advantage of limiting the
      influence of passive natural temperature gradients and of yielding more stable
      zero-flux references at night. By analogy with the CTD method, the transient
      method was first calibrated on synthetic porous material (sawdust) on the
      assumption that the relationship was independent of the woody species. Here, our
      concern was to test the latter hypothesis with a 10-min heating time in three
      tropical species: Hevea brasiliensis Mull. Arg., Mangifera indica L. and Citrus
      maxima Merr. A complementary objective was to compare the field estimates of
      daily transpiration for mature rubber trees with estimates based on a simplified
      soil water balance in the dry season. The calibration experiments were carried
      out in the laboratory on cut stems using an HPFM device and gravimetric control
      of water flow up to 5 L dm(-2) h(-1). Nineteen response curves were assessed on
      fully conductive xylem, combining 11 cut stems and two probes. The field
      evaluation comprised five periods from November 2007 to February 2008. Estimates
      of daily transpiration from the measurement of sap flow were based on the 41
      sensors set up on 11 trees. Soil water depletion was monitored by neutron probe
      and 12 access tubes to a depth of 1.8 m. The calibrations confirmed that the
      response of the transient thermal index to flow density was independent of the
      woody species that were tested. The best fit was a simple linear response (R(2) =
      0.88, n = 276 and P < 0.0001). The previous calibration performed by Do and
      Rocheteau (2002b) on sawdust fell within the variability of the multi-species
      calibration; however, there were substantial differences with the average curve
      at extreme flow rates. Field comparison with soil water depletion in the dry
      season validated to a reasonable extent the absolute estimates of transpiration
      acquired with the 10-min TTD method. In conclusion, evidence for the independence
      of calibration from woody species and the simple linear response of the thermal
      index strengthen the interest of the TTD method with 10-min heating.

PMID- 19864261
TI  - The differential response of photosynthesis to high temperature for a boreal and
      temperate Populus species relates to differences in Rubisco activation and
      Rubisco activase properties.
AB  - Significant inhibition of photosynthesis occurs at temperatures only a few
      degrees (<or= 10 degrees C) above the optimum, resulting in a considerable loss
      of potential productivity. Most studies of heat stress have focused on crop or
      weedy annual plants, whereas similar studies with trees have been limited in
      number. As temperature is a major factor limiting the geographic ranges of most
      plants, the aim of this study was to use two Populus species adapted to
      contrasting thermal environments for determining the factors that constrain
      photosynthetic assimilation (A) under moderate heat stress in tree species.
      Consistent with its native range in temperate regions, Populus deltoides Bartr.
      ex Marsh. exhibited a significantly higher temperature optimum for A than did
      Populus balsamifera L., a boreal species. The higher A exhibited by P. deltoides
      at 33-40 degrees C compared to that for P. balsamifera was associated with a
      higher activation state of Rubisco and correlated with a higher ATPase activity
      of Rubisco activase. The temperature response of minimal chlorophyll a
      fluorescence for darkened leaves was similar for both species and was not
      consistent with a thylakoid lipid phase change contributing to the decline in A
      in the range of 30-40 degrees C. Taken together, these data support the idea that
      the differences in the temperature response of A for the two Populus species
      could be attributed to the differences in the response of Rubisco activation and
      ultimately to the thermal properties of Rubisco activase. That the primary
      sequence of Rubisco activase differed between the species, especially in regions
      associated with ATPase activity and Rubisco recognition, indicates that the
      genotypic differences in Rubisco activase might underlie the differences in the
      heat sensitivity of Rubisco activase and photosynthesis at moderately high
      temperatures.

PMID- 19864262
TI  - Phenopedia and Genopedia: disease-centered and gene-centered views of the
      evolving knowledge of human genetic associations.
AB  - SUMMARY: We developed web-based applications that encourage the exploration of
      the literature on human genetic associations by using a database that is
      continuously updated from PubMed. These applications provide user-friendly
      interfaces for searching summarized information on human genetic associations,
      using either genes or diseases as the starting point. AVAILABILITY: Phenopedia
      and Genopedia can be freely accessed at
      http://www.hugenavigator.net/HuGENavigator/startPagePhenoPedia.do and
      http://www.hugenavigator.net/HuGENavigator/startPagePedia.do, respectively.

PMID- 19864263
TI  - Directional orientation of birds by the magnetic field under different light
      conditions.
AB  - This paper reviews the directional orientation of birds with the help of the
      geomagnetic field under various light conditions. Two fundamentally different
      types of response can be distinguished. (i) Compass orientation controlled by the
      inclination compass that allows birds to locate courses of different origin. This
      is restricted to a narrow functional window around the total intensity of the
      local geomagnetic field and requires light from the short-wavelength part of the
      spectrum. The compass is based on radical-pair processes in the right eye;
      magnetite-based receptors in the beak are not involved. Compass orientation is
      observed under 'white' and low-level monochromatic light from ultraviolet (UV) to
      about 565 nm green light. (ii) 'Fixed direction' responses occur under artificial
      light conditions such as more intense monochromatic light, when 590 nm yellow
      light is added to short-wavelength light, and in total darkness. The
      manifestation of these responses depends on the ambient light regime and is
      'fixed' in the sense of not showing the normal change between spring and autumn;
      their biological significance is unclear. In contrast to compass orientation,
      fixed-direction responses are polar magnetic responses and occur within a wide
      range of magnetic intensities. They are disrupted by local anaesthesia of the
      upper beak, which indicates that the respective magnetic information is mediated
      by iron-based receptors located there. The influence of light conditions on the
      two types of response suggests complex interactions between magnetoreceptors in
      the right eye, those in the upper beak and the visual system.

PMID- 19864264
TI  - Systemic risk: the dynamics of model banking systems.
AB  - The recent banking crises have made it clear that increasingly complex strategies
      for managing risk in individual banks have not been matched by corresponding
      attention to overall systemic risks. We explore some simple mathematical
      caricatures for 'banking ecosystems', with emphasis on the interplay between the
      characteristics of individual banks (capital reserves in relation to total
      assets, etc.) and the overall dynamical behaviour of the system. The results are
      discussed in relation to potential regulations aimed at reducing systemic risk.

PMID- 19864267
TI  - Transient virulence of emerging pathogens.
AB  - Should emerging pathogens be unusually virulent? If so, why? Existing theories of
      virulence evolution based on a tradeoff between high transmission rates and long
      infectious periods imply that epidemic growth conditions will select for higher
      virulence, possibly leading to a transient peak in virulence near the beginning
      of an epidemic. This transient selection could lead to high virulence in emerging
      pathogens. Using a simple model of the epidemiological and evolutionary dynamics
      of emerging pathogens, along with rough estimates of parameters for pathogens
      such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we
      estimated the potential magnitude and timing of such transient virulence peaks.
      Pathogens that are moderately evolvable, highly transmissible, and highly
      virulent at equilibrium could briefly double their virulence during an epidemic;
      thus, epidemic-phase selection could contribute significantly to the virulence of
      emerging pathogens. In order to further assess the potential significance of this
      mechanism, we bring together data from the literature for the shapes of tradeoff
      curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and
      the level of genetic variation for virulence for one (myxomatosis). We discuss
      the need for better data on tradeoff curves and genetic variance in order to
      evaluate the plausibility of various scenarios of virulence evolution.

PMID- 19864265
TI  - Bone tissue engineering therapeutics: controlled drug delivery in three
      dimensional scaffolds.
AB  - This paper provides an extensive overview of published studies on the development
      and applications of three-dimensional bone tissue engineering (TE) scaffolds with
      potential capability for the controlled delivery of therapeutic drugs. Typical
      drugs considered include gentamicin and other antibiotics generally used to
      combat osteomyelitis, as well as anti-inflammatory drugs and bisphosphonates, but
      delivery of growth factors is not covered in this review. In each case reviewed,
      special attention has been given to the technology used for controlling the
      release of the loaded drugs. The possibility of designing multifunctional three
      dimensional bone TE scaffolds for the emerging field of bone TE therapeutics is
      discussed. A detailed summary of drugs included in three-dimensional scaffolds
      and the several approaches developed to combine bioceramics with various
      polymeric biomaterials in composites for drug-delivery systems is included. The
      main results presented in the literature are discussed and the remaining
      challenges in the field are summarized with suggestions for future research
      directions.

PMID- 19864268
TI  - Size-dependent leaf area ratio in plant twigs: implication for leaf size
      optimization.
AB  - BACKGROUND AND AIMS: Although many hypotheses have been proposed to explain
      variation in leaf size, the mechanism underlying the variation remains not fully
      understood. To help understand leaf size variation, the cost/benefit of twig size
      was analysed, since, according to Corner's rule, twig size is positively
      correlated with the size of appendages the twig bears. METHODS: An extensive
      survey of twig functional traits, including twig (current-year shoots including
      one stem and few leaves) and leaf size (individual leaf area and mass), was
      conducted for 234 species from four broadleaved forests. The scaling relationship
      between twig mass and leaf area was determined using standardized major axis
      regression and phylogenetic independent comparative analyses. KEY RESULTS: Leaf
      area was found to scale positively and allometrically with both stem and twig
      mass (stem mass plus leaf mass) with slopes significantly smaller than 1.0,
      independent of life form and habitat type. Thus, the leaf area ratio (the ratio
      of total leaf area to stem or twig mass) decreases with increasing twig size.
      Moreover, the leaf area ratio correlated negatively with individual leaf mass.
      The results of phylogenetic independent comparativeanalyses were consistent with
      the correlations. Based on the above results, a simple model for twig size
      optimization was constructed, from which it is postulated that large leaf size
      twig size may be favoured when leaf photosynthetic capacity is high and/or when
      leaf life span and/or stem longevity are long. The model's predictions are
      consistent with leaf size variation among habitats, in which leaf size tends to
      be small in poor habitats with a low primary productivity. The model also
      explains large variations in leaf size within habitats for which leaf longevity
      and stem longevity serve as important determinants. CONCLUSIONS: The diminishing
      returns in the scaling of total leaf area with twig size can be explained in
      terms of a very simple model on twig siz

PMID- 19864269
TI  - Host ant independent oviposition in the parasitic butterfly Maculinea alcon.
AB  - Parasitic Maculinea alcon butterflies can only develop in nests of a subset of
      available Myrmica ant species, so female butterflies have been hypothesized to
      preferentially lay eggs on plants close to colonies of the correct host ants.
      Previous correlational investigations of host-ant-dependent oviposition in this
      and other Maculinea species have, however, shown equivocal results, leading to a
      long-term controversy over support for this hypothesis. We therefore conducted a
      controlled field experiment to study the egg-laying behaviour of M. alcon.
      Matched potted Gentiana plants were set out close to host-ant nests and non-host
      ant nests, and the number and position of eggs attached were assessed. Our
      results show no evidence for host-ant-based oviposition in M. alcon, but support
      an oviposition strategy based on plant characteristics. This suggests that
      careful management of host-ant distribution is necessary for conservation of this
      endangered butterfly.

PMID- 19864266
TI  - A review of tissue-engineered skin bioconstructs available for skin
      reconstruction.
AB  - Situations where normal autografts cannot be used to replace damaged skin often
      lead to a greater risk of mortality, prolonged hospital stay and increased
      expenditure for the National Health Service. There is a substantial need for
      tissue-engineered skin bioconstructs and research is active in this field.
      Significant progress has been made over the years in the development and clinical
      use of bioengineered components of the various skin layers. Off-the-shelf
      availability of such constructs, or production of sufficient quantities of
      biological materials to aid rapid wound closure, are often the only means to help
      patients with major skin loss. The aim of this review is to describe those
      materials already commercially available for clinical use as well as to give a
      short insight to those under development. It seeks to provide skin
      scientists/tissue engineers with the information required to not only develop in
      vitro models of skin, but to move closer to achieving the ultimate goal of an off
      the-shelf, complete full-thickness skin replacement.

PMID- 19864270
TI  - Extrafloral nectar content alters foraging preferences of a predatory ant.
AB  - We tested whether the carbohydrate and amino acid content of extrafloral nectar
      affected prey choice by a predatory ant. Fire ants, Solenopsis invicta, were
      provided with artificial nectar that varied in the presence of carbohydrates and
      amino acids and were then provided with two prey items that differed in
      nutritional content, female and male crickets. Colonies of fire ants provided
      with carbohydrate supplements consumed less of the female crickets and frequently
      did not consume the high-lipid ovaries of female crickets. Colonies of fire ants
      provided with amino acid supplements consumed less of the male crickets. While a
      number of studies have shown that the presence of extrafloral nectar or honeydew
      can affect ant foraging activity, these results suggest that the nutritional
      composition of extrafloral nectar is also important and can affect subsequent
      prey choice by predatory ants. Our results suggest that, by altering the
      composition of extrafloral nectar, plants could manipulate the prey preferences
      of ants foraging on them.

PMID- 19864272
TI  - With his memory magnetically erased, a monkey knows he is uncertain.
AB  - Although intelligence is associated with what one knows, it is also important to
      recognize and to respond adaptively when one is uncertain. This competency has
      been examined developmentally and comparatively, but it is difficult to
      distinguish between objective versus subjective cues to which organisms may
      respond. In this study, transcranial magnetic stimulation was used to disrupt
      cognitive processing by a rhesus monkey (Macaca mulatta) in a computerized
      divided visual field memory task. When magnetic stimulation disrupted neural
      activity in the cerebral hemisphere that initially processed the visual images,
      recognition accuracy declined and use of the uncertain response significantly
      increased, relative to control conditions. Thus, the monkey tended to respond
      adaptively when he did not know the answer--where uncertainty was produced by
      targeted disruption of the neural processing of a stimulus--even in the absence
      of external, objective cues to corroborate his subjective, metacognitive
      assessment of uncertainty.

PMID- 19864271
TI  - Mountain lions prey selectively on prion-infected mule deer.
AB  - The possibility that predators choose prey selectively based on age or condition
      has been suggested but rarely tested. We examined whether mountain lions (Puma
      concolor) selectively prey upon mule deer (Odocoileus hemionus) infected with
      chronic wasting disease, a prion disease. We located kill sites of mountain lions
      in the northern Front Range of Colorado, USA, and compared disease prevalence
      among lion-killed adult (> or =2 years old) deer with prevalence among sympatric
      deer taken by hunters in the vicinity of kill sites. Hunter-killed female deer
      were less likely to be infected than males (odds ratios (OR) = 0.2, 95%
      confidence intervals (CI) = 0.1-0.6; p = 0.015). However, both female (OR = 8.5,
      95% CI = 2.3-30.9) and male deer (OR = 3.2, 95% CI = 1-10) killed by a mountain
      lion were more likely to be infected than same-sex deer killed in the vicinity by
      a hunter (p < 0.001), suggesting that mountain lions in this area actively
      selected prion-infected individuals when targeting adult mule deer as prey items.

PMID- 19864273
TI  - Ontogeny of long bone geometry in capuchin monkeys (Cebus albifrons and Cebus
      apella): implications for locomotor development and life history.
AB  - Studies of a diverse array of animals have found that young individuals often
      have robust bones for their body size (i.e. augmented cross-sectional
      dimensions), limiting fracture risk despite general musculoskeletal immaturity.
      However, previous research has focused primarily on precocial taxa (e.g. rodents,
      lagomorphs, bovids, goats and emu). In this study, we examined the ontogenetic
      scaling of humeral and femoral cross-sectional robusticity in a mixed
      longitudinal sample of two slow-growing, behaviourally altricial capuchin
      monkeys. Results showed that, when regressed against biomechanically appropriate
      size variables (i.e. the product of body mass and bone length), humeral and
      femoral bending strengths generally scale with negative allometry, matching the
      scaling patterns observed in previous studies of more precocial mammals.
      Additionally, bone strength relative to predicted loads (e.g. 'safety factors')
      peaks at birth and rapidly decreases during postnatal growth, falling to less
      than 5 per cent of peak values by weaning age. We suggest that increased safety
      factors during early ontogeny may be an adaptation to mitigate injury from
      falling during initial locomotor efforts. Overall, the results presented here
      suggest that ontogenetic declines in relative long bone strength may represent a
      common pattern among mammals that is perhaps preadaptive for different purposes
      among different lineages.

PMID- 19864274
TI  - Three-dimensional resting behaviour of northern elephant seals: drifting like a
      falling leaf.
AB  - During their long migrations through the Pacific, northern elephant seals,
      Mirounga angustirostris, never haul out on land and they rarely spend more than a
      few minutes at a time at the surface. They are almost constantly making
      repetitive, deep dives, raising the question of when do they rest? One type of
      dive, the drift dive, characterized by a time-depth profile with a phase of lower
      than average descent speed is believed to be a resting dive. To examine the
      behaviour of seals during drift dives, we measured body position and three
      dimensional diving paths of six juvenile seals. We found that seals rolled over
      and sank on their backs during the drift phase, wobbling periodically so that
      they resembled a falling leaf. This enabled seals to drastically slow their
      descent rate, possibly so that negatively buoyant seals can rest without ending
      up in the abyss. This reduces the work required to return to the surface to
      breath, and allows them time to rest, process food or possibly sleep during the
      descent phase of these dives where they are probably less susceptible to
      predation.

PMID- 19864275
TI  - Giant panda conservation science: how far we have come.
AB  - The giant panda is a conservation icon, but science has been slow to take up its
      cause in earnest. In the past decade, researchers have been making up for lost
      time, as reflected in the flurry of activity reported at the symposium
      Conservation Science for Giant Pandas and Their Habitat at the 2009 International
      Congress for Conservation Biology (ICCB) in Beijing. In reports addressing topics
      ranging from spatial ecology to molecular censusing, from habitat recovery in
      newly established reserves to earthquake-induced habitat loss, from new insights
      into factors limiting carrying capacity to the uncertain effects of climate
      change, this symposium displayed the vibrant and blossoming application of
      science to giant panda conservation. Collectively, we find that we have come a
      long way, but we also reach an all-too-familiar conclusion: the more we know, the
      more challenges are revealed. While many earlier findings are supported, many of
      our assumptions are debatable. Here we discuss recent advancements in
      conservation science for giant pandas and suggest that the way forward is more
      direct application of emerging science to management and policy.

PMID- 19864276
TI  - Visual cues and parental favouritism in a nocturnal bird.
AB  - Visual signals are crucial for parent-offspring communication, although their
      functioning has been neglected for nocturnal birds. Here, we investigated
      parental preference for nestling coloration in nocturnal conditions--a question
      hitherto unexplored--in a nocturnal raptor, the scops owl (Otus scops). We
      assessed how parents allocated food during the night in relation to a
      manipulation of ultraviolet (UV) reflectance of the cere (skin above the beak) of
      their offspring. Reflectance of the cere shows a marked peak in the UV part of
      the spectrum, and location of the UV peak is related to nestling body mass (i.e.
      heavier nestlings have a UV peak at lower wavelengths). We found evidence of
      parental bias in favour of lighter offspring: UV-reduced nestlings gained more
      weight during the night than their control siblings. This study provides the
      first experimental evidence of the use of visual cues for parent-offspring
      communication in a nocturnal bird.

PMID- 19864277
TI  - Tropical warming and the dynamics of endangered primates.
AB  - Many primate species are severely threatened, but little is known about the
      effects of global warming and the associated intensification of El Nino events on
      primate populations. Here, we document the influences of the El Nino southern
      oscillation (ENSO) and hemispheric climatic variability on the population
      dynamics of four genera of ateline (neotropical, large-bodied) primates. All
      ateline genera experienced either an immediate or a lagged negative effect of El
      Nino events. ENSO events were also found to influence primate resource levels
      through neotropical arboreal phenology. Furthermore, frugivorous primates showed
      a high degree of interspecific population synchrony over large scales across
      Central and South America attributable to the recent trends in large-scale
      climate. These results highlight the role of large-scale climatic variation and
      trends in ateline primate population dynamics, and emphasize that global warming
      could pose additional threats to the persistence of multiple species of
      endangered primates.

PMID- 19864278
TI  - Individual consistency in flight initiation distances in burrowing owls: a new
      hypothesis on disturbance-induced habitat selection.
AB  - Individuals often consistently differ in personalities and behaviours that allow
      them to cope with environmental variation. Flight initiation distance (FID) has
      been measured in a variety of taxa as an estimate of the risk that an individual
      is willing to take when facing a predator. FID has been used to test life-history
      trade-offs related to anti-predatory behaviour and for conservation purposes such
      as to establish buffer zones to minimize human disturbance, given its species
      specific consistency. Individual consistency in FID, however, has been largely
      overlooked. Here we show that, even after controlling for several confounding
      effects, this behaviour has a strong individual component (repeatability = 0.84
      0.92) in a bird species, leaving a small margin for behavioural flexibility. We
      hypothesize that individuals may distribute themselves among breeding sites
      depending on their individual susceptibility to human disturbance. This habitat
      selection hypothesis merits further research, given its implications on both
      evolutionary and applied ecology research. For example, selection of human
      tolerant phenotypes may be promoted through the humanization of habitats
      occurring worldwide, and when population means instead of individual variability
      in FID are considered for designing buffer zones to reduce human impacts on
      wildlife.

PMID- 19864279
TI  - The role of population heterogeneity and human mobility in the spread of pandemic
      influenza.
AB  - Little is known on how different levels of population heterogeneity and different
      patterns of human mobility affect the course of pandemic influenza in terms of
      timing and impact. By employing a large-scale spatially explicit individual-based
      model, founded on a highly detailed model of the European populations and on a
      careful analysis of air and railway transportation data, we provide quantitative
      measures of the influence of such factors at the European scale. Our results show
      that Europe has to be prepared to face a rapid diffusion of a pandemic influenza,
      because of the high mobility of the population, resulting in the early
      importation of the first cases from abroad and highly synchronized local
      epidemics. The impact of the epidemic in European countries is highly variable
      because of the marked differences in the sociodemographic structure of European
      populations. R(0), cumulative attack rate and peak daily attack rate depend
      heavily on sociodemographic parameters, such as the size of household groups and
      the fraction of workers and students in the population.

PMID- 19864281
TI  - The effect of personality on social foraging: shy barnacle geese scrounge more.
AB  - Animals foraging in groups can either search for food themselves (producing) or
      search for the food discoveries of other individuals (scrounging). Tactic use in
      producer-scrounger games is partly flexible but individuals tend to show
      consistency in tactic use under different conditions suggesting that personality
      might play a role in tactic use in producer-scrounger games. Here we studied the
      use of producing and scrounging tactics by bold and shy barnacle geese (Branta
      leucopsis), where boldness is a personality trait known to be repeatable over
      time in this species. We defined individuals as bold, shy or intermediate based
      on two novel object tests. We scored the frequency of finding food patches (the
      outcome of investing in producing) and joining patches (the outcome of investing
      in scrounging) by bold and shy individuals and their feeding time. Shy
      individuals had a higher frequency of joining than bold individuals,
      demonstrating for the first time that personality is associated with tactic use
      in a producer-scrounger game. Bold individuals tended to spend more time feeding
      than shy individuals. Our results highlight the importance of including
      individual behavioural variation in models of producer-scrounger games.

PMID- 19864280
TI  - Refugia revisited: individualistic responses of species in space and time.
AB  - Climate change in the past has led to significant changes in species'
      distributions. However, how individual species respond to climate change depends
      largely on their adaptations and environmental tolerances. In the Quaternary,
      temperate-adapted taxa are in general confined to refugia during glacials while
      cold-adapted taxa are in refugia during interglacials. In the Northern
      Hemisphere, evidence appears to be mounting that in addition to traditional
      southern refugia for temperate species, cryptic refugia existed in the North
      during glacials. Equivalent cryptic southern refugia, to the south of the more
      conventional high-latitude polar refugia, exist in montane areas during periods
      of warm climate, such as the current interglacial. There is also a
      continental/oceanic longitudinal gradient, which should be included in a more
      complete consideration of the interaction between species ranges and climates.
      Overall, it seems clear that there is large variation in both the size of refugia
      and the duration during which species are confined to them. This has implications
      for the role of refugia in the evolution of species and their genetic diversity.

PMID- 19864282
TI  - Sexual conflict inhibits female mate choice for major histocompatibility complex
      dissimilarity in Chinook salmon.
AB  - In many species females prefer major histocompatibility complex (MHC) dissimilar
      mates, which may improve offspring resistance to pathogens. However, sexual
      conflict may interfere with female preference when males attempt to mate with all
      females, regardless of compatibility. Here we used semi-natural spawning channels
      to examine how mating behaviour and genetic similarity at the MHC class II
      peptide binding region affected parentage patterns in Chinook salmon
      (Oncorhynchus tshawytscha). We found that females directed aggression at more MHC
      similar males than expected by chance, providing a possible mechanism of female
      MHC choice in salmon. Males also directed aggression towards MHC-similar females,
      which was consistent with males harassing unreceptive mates. Males' aggression
      was positively correlated with their reproductive success, and it appeared to
      overcome female aversion to mating with MHC-similar males, as females who were
      the target of high levels of male aggression had lower than expected MHC
      divergence in their offspring. Indeed, offspring MHC divergence was highest when
      the sex ratio was female-biased and male harassment was likely to be less
      intense. These data suggest that male harassment can reduce female effectiveness
      in selecting MHC-compatible mates, and sexual conflict can thus have an indirect
      cost to females.

PMID- 19864283
TI  - Facial cues of dominance modulate the short-term gaze-cuing effect in human
      observers.
AB  - Responding appropriately to gaze cues is essential for fluent social interaction,
      playing a crucial role in social learning, collaboration, threat assessment and
      understanding others' intentions. Previous research has shown that responses to
      gaze cues can be studied by investigating the gaze-cuing effect (i.e. the
      tendency for observers to respond more quickly to targets in locations that were
      cued by others' gaze than to uncued targets). A recent study demonstrating that
      macaques demonstrate larger gaze-cuing effects when viewing dominant conspecifics
      than when viewing subordinate conspecifics suggests that cues of dominance
      modulate the gaze-cuing effect in at least one primate species. Here, we show a
      similar effect of facial cues associated with dominance on gaze cuing in human
      observers: at short viewing times, observers demonstrated a greater cuing effect
      for gaze cues from masculinized (i.e. dominant) faces than from feminized (i.e.
      subordinate) faces. Moreover, this effect of facial masculinity on gaze cuing
      decreased as viewing time was increased, suggesting that the effect is driven by
      involuntary responses. Our findings suggest that the mechanisms that underpin
      reflexive gaze cuing evolved to be sensitive to facial cues of others' dominance,
      potentially because such differential gaze cuing promoted desirable outcomes from
      encounters with dominant individuals.

PMID- 19864284
TI  - Intensive fish farming and the evolution of pathogen virulence: the case of
      columnaris disease in Finland.
AB  - Ecological changes affect pathogen epidemiology and evolution and may trigger the
      emergence of novel diseases. Aquaculture radically alters the ecology of fish and
      their pathogens. Here we show an increase in the occurrence of the bacterial fish
      disease Flavobacterium columnare in salmon fingerlings at a fish farm in northern
      Finland over 23 years. We hypothesize that this emergence was owing to
      evolutionary changes in bacterial virulence. We base this argument on several
      observations. First, the emergence was associated with increased severity of
      symptoms. Second, F. columnare strains vary in virulence, with more lethal
      strains inducing more severe symptoms prior to death. Third, more virulent
      strains have greater infectivity, higher tissue-degrading capacity and higher
      growth rates. Fourth, pathogen strains co-occur, so that strains compete. Fifth,
      F. columnare can transmit efficiently from dead fish, and maintain infectivity in
      sterilized water for months, strongly reducing the fitness cost of host death
      likely experienced by the pathogen in nature. Moreover, this saprophytic
      infectiousness means that chemotherapy strongly select for strains that rapidly
      kill their hosts: dead fish remain infectious; treated fish do not. Finally, high
      stocking densities of homogeneous subsets of fish greatly enhance transmission
      opportunities. We suggest that fish farms provide an environment that promotes
      the circulation of more virulent strains of F. columnare. This effect is
      intensified by the recent increases in summer water temperature. More generally,
      we predict that intensive fish farming will lead to the evolution of more
      virulent pathogens.

PMID- 19864285
TI  - Horizontal gene transfer in evolution: facts and challenges.
AB  - The contribution of horizontal gene transfer to evolution has been controversial
      since it was suggested to be a force driving evolution in the microbial world. In
      this paper, I review the current standpoint on horizontal gene transfer in
      evolutionary thinking and discuss how important horizontal gene transfer is in
      evolution in the broad sense, and particularly in prokaryotic evolution. I review
      recent literature, asking, first, which processes are involved in the
      evolutionary success of transferred genes and, secondly, about the extent of
      horizontal gene transfer towards different evolutionary times. Moreover, I
      discuss the feasibility of reconstructing ancient phylogenetic relationships in
      the face of horizontal gene transfer. Finally, I discuss how horizontal gene
      transfer fits in the current neo-Darwinian evolutionary paradigm and conclude
      there is a need for a new evolutionary paradigm that includes horizontal gene
      transfer as well as other mechanisms in the explanation of evolution.

PMID- 19864286
TI  - Culture-gene coevolution of individualism-collectivism and the serotonin
      transporter gene.
AB  - Culture-gene coevolutionary theory posits that cultural values have evolved, are
      adaptive and influence the social and physical environments under which genetic
      selection operates. Here, we examined the association between cultural values of
      individualism-collectivism and allelic frequency of the serotonin transporter
      functional polymorphism (5-HTTLPR) as well as the role this culture-gene
      association may play in explaining global variability in prevalence of pathogens
      and affective disorders. We found evidence that collectivistic cultures were
      significantly more likely to comprise individuals carrying the short (S) allele
      of the 5-HTTLPR across 29 nations. Results further show that historical pathogen
      prevalence predicts cultural variability in individualism-collectivism owing to
      genetic selection of the S allele. Additionally, cultural values and frequency of
      S allele carriers negatively predict global prevalence of anxiety and mood
      disorder. Finally, mediation analyses further indicate that increased frequency
      of S allele carriers predicted decreased anxiety and mood disorder prevalence
      owing to increased collectivistic cultural values. Taken together, our findings
      suggest culture-gene coevolution between allelic frequency of 5-HTTLPR and
      cultural values of individualism-collectivism and support the notion that
      cultural values buffer genetically susceptible populations from increased
      prevalence of affective disorders. Implications of the current findings for
      understanding culture-gene coevolution of human brain and behaviour as well as
      how this coevolutionary process may contribute to global variation in pathogen
      prevalence and epidemiology of affective disorders, such as anxiety and
      depression, are discussed.

PMID- 19864287
TI  - Thermoregulatory behaviour affects prevalence of chytrid fungal infection in a
      wild population of Panamanian golden frogs.
AB  - Predicting how climate change will affect disease dynamics requires an
      understanding of how the environment affects host-pathogen interactions. For
      amphibians, global declines and extinctions have been linked to a pathogenic
      chytrid fungus, Batrachochytrium dendrobatidis. Using a combination of body
      temperature measurements and disease assays conducted before and after the
      arrival of B. dendrobatidis, this study tested the hypothesis that body
      temperature affects the prevalence of infection in a wild population of
      Panamanian golden frogs (Atelopus zeteki). The timing of first detection of the
      fungus was consistent with that of a wave of epidemic infections spreading south
      and eastward through Central America. During the epidemic, many golden frogs
      modified their thermoregulatory behaviour, raising body temperatures above their
      normal set point. Odds of infection decreased with increasing body temperature,
      demonstrating that even slight environmental or behavioural changes have the
      potential to affect an individual's vulnerability to infection. The thermal
      dependency of the relationship between B. dendrobatidis and its amphibian hosts
      demonstrates how the progression of an epidemic can be influenced by complex
      interactions between host and pathogen phenotypes and the environments in which
      they are found.

PMID- 19864288
TI  - Grandma plays favourites: X-chromosome relatedness and sex-specific childhood
      mortality.
AB  - Biologists use genetic relatedness between family members to explain the
      evolution of many behavioural and developmental traits in humans, including
      altruism, kin investment and longevity. Women's post-menopausal longevity in
      particular is linked to genetic relatedness between family members. According to
      the 'grandmother hypothesis', post-menopausal women can increase their genetic
      contribution to future generations by increasing the survivorship of their
      grandchildren. While some demographic studies have found evidence for this,
      others have found little support for it. Here, we re-model the predictions of the
      grandmother hypothesis by examining the genetic relatedness between grandmothers
      and grandchildren. We use this new model to re-evaluate the grandmother effect in
      seven previously studied human populations. Boys and girls differ in the per cent
      of genes they share with maternal versus paternal grandmothers because of
      differences in X-chromosome inheritance. Here, we demonstrate a relationship
      between X-chromosome inheritance and grandchild mortality in the presence of a
      grandmother. With this sex-specific and X-chromosome approach to interpreting
      mortality rates, we provide a new perspective on the prevailing theory for the
      evolution of human female longevity. This approach yields more consistent support
      for the grandmother hypothesis, and has implications for the study of human
      evolution.

PMID- 19864289
TI  - Caste-specific expression of genetic variation in the size of antibiotic
      producing glands of leaf-cutting ants.
AB  - Social insect castes represent some of the most spectacular examples of
      phenotypic plasticity, with each caste being associated with different
      environmental conditions during their life. Here we examine the level of genetic
      variation in different castes of two polyandrous species of Acromyrmex leaf
      cutting ant for the antibiotic-producing metapleural gland, which has a major
      role in defence against parasites. Gland size increases allometrically. The small
      workers that play the main role in disease defence have relatively large glands
      compared with larger workers, while the glands of gynes are substantially larger
      than those of any workers, for their body size. The gland size of large workers
      varies significantly between patrilines in both Acromyrmex echinatior and
      Acromyrmex octospinosus. We also examined small workers and gynes in A.
      echinatior, again finding genetic variation in gland size in these castes. There
      were significant positive relationships between the gland sizes of patrilines in
      the different castes, indicating that the genetic mechanism underpinning the
      patriline variation has remained similar across phenotypes. The level of
      expressed genetic variation decreased from small workers to large workers to
      gynes. This is consistent with the hypothesis that there is individual selection
      on disease defence in founding queens and colony-level selection on disease
      defence in the worker castes.

PMID- 19864290
TI  - Interspecific aggression and character displacement of competitor recognition in
      Hetaerina damselflies.
AB  - In zones of sympatry between closely related species, species recognition errors
      in a competitive context can cause character displacement in agonistic signals
      and competitor recognition functions, just as species recognition errors in a
      mating context can cause character displacement in mating signals and mate
      recognition. These two processes are difficult to distinguish because the same
      traits can serve as both agonistic and mating signals. One solution is to test
      for sympatric shifts in recognition functions. We studied competitor recognition
      in Hetaerina damselflies by challenging territory holders with live tethered
      conspecific and heterospecific intruders. Heterospecific intruders elicited less
      aggression than conspecific intruders in species pairs with dissimilar wing
      coloration (H. occisa/H. titia, H. americana/H. titia) but not in species pairs
      with similar wing coloration (H. occisa/H. cruentata, H. americana/H. cruentata).
      Natural variation in the area of black wing pigmentation on H. titia intruders
      correlated negatively with heterospecific aggression. To directly examine the
      role of wing coloration, we blackened the wings of H. occisa or H. americana
      intruders and measured responses of conspecific territory holders. This treatment
      reduced territorial aggression at multiple sites where H. titia is present, but
      not at allopatric sites. These results provide strong evidence for agonistic
      character displacement.

PMID- 19864291
TI  - Are fast explorers slow reactors? Linking personality type and anti-predator
      behaviour.
AB  - Response delays to predator attack may be adaptive, suggesting that latency to
      respond does not always reflect predator detection time, but can be a decision
      based on starvation-predation risk trade-offs. In birds, some anti-predator
      behaviours have been shown to be correlated with personality traits such as
      activity level and exploration. Here, we tested for a correlation between
      exploration behaviour and response latency time to a simulated fish predator
      attack in a fish species, juvenile convict cichlids (Amatitlania nigrofasciata).
      Individual focal fish were subjected to a standardized attack by a robotic fish
      predator while foraging, and separately given two repeated trials of exploration
      of a novel environment. We found a strong positive correlation between
      exploration and time taken to respond to the predator model. Fish that were fast
      to explore the novel environment were slower to respond to the predator. Our
      study therefore provides some of the first experimental evidence for a link
      between exploration behaviour and predator-escape behaviour. We suggest that
      different behavioural types may differ in how they partition their attention
      between foraging and anti-predator vigilance.

PMID- 19864292
TI  - Female's courtship threshold allows intruding males to mate with reduced effort.
AB  - Female decision rules can influence the nature and intensity of sexual selection
      on males, but empirical demonstrations of rules underlying choice are rare. We
      hypothesized that female choice is largely based on a courtship duration
      threshold in the Australian redback spider (Latrodectus hasselti) because females
      kill males before copulation is complete (premature cannibalism) and reduce their
      paternity if courtship is brief. We used published data to infer that the
      female's threshold is approximately 100 min of courtship. We support this
      hypothesis by showing that premature cannibalism is common when the male's
      courtship duration is below this threshold, but is infrequent and unrelated to
      duration once courtship exceeds the threshold. We then ask whether females
      discriminate the source of courtship when rival males compete, as this will
      determine the effect of the threshold on male competitive tactics. We staged
      competitions where 'resident' males initially courted females in the absence of
      competition, exceeding the courtship threshold before 'intruding' males were
      introduced. Intruding males mated rapidly but were not prematurely cannibalized
      by females, in contrast to cases where competition starts before the threshold is
      surpassed. This suggests females do not distinguish which male satisfies the
      threshold, allowing intruders to parasitize the courtship efforts of residents.
      To our knowledge, such exploitation of mating efforts by rival males mediated by
      a female choice threshold has not been demonstrated elsewhere. Ironically, this
      female choice threshold and the attendant possibility of courtship parasitism may
      lead to selection for lower-quality males to recognize and seek out (rather than
      avoid) webs in which competitors are already present.

PMID- 19864293
TI  - Treatment-based Markov chain models clarify mechanisms of invasion in an invaded
      grassland community.
AB  - What are the relative roles of mechanisms underlying plant responses in grassland
      communities invaded by both plants and mammals? What type of community can we
      expect in the future given current or novel conditions? We address these
      questions by comparing Markov chain community models among treatments from a
      field experiment on invasive species on Robinson Crusoe Island, Chile. Because of
      seed dispersal, grazing and disturbance, we predicted that the exotic European
      rabbit (Oryctolagus cuniculus) facilitates epizoochorous exotic plants (plants
      with seeds that stick to the skin an animal) at the expense of native plants. To
      test our hypothesis, we crossed rabbit exclosure treatments with disturbance
      treatments, and sampled the plant community in permanent plots over 3 years. We
      then estimated Markov chain model transition probabilities and found significant
      differences among treatments. As hypothesized, this modelling revealed that
      exotic plants survive better in disturbed areas, while natives prefer no rabbits
      or disturbance. Surprisingly, rabbits negatively affect epizoochorous plants.
      Markov chain dynamics indicate that an overall replacement of native plants by
      exotic plants is underway. Using a treatment-based approach to multi-species
      Markov chain models allowed us to examine the changes in the importance of
      mechanisms in response to experimental impacts on communities.

PMID- 19864295
TI  - Differential dynamics of amino acid release in the amygdala and olfactory cortex
      during odor fear acquisition as revealed with simultaneous high temporal
      resolution microdialysis.
AB  - Although the amygdala seems to be essential to the formation and storage of fear
      memories, it might store only some aspects of the aversive event and facilitate
      the storage of more specific sensory aspects in cortical areas. We addressed the
      time course of amygdala and cortical activation in the context of odor fear
      conditioning in rats. Using high temporal resolution (1-min sampling)
      intracerebral microdialysis, we investigated the dynamics of glutamate and GABA
      fluctuations simultaneously in basolateral amygdala (BLA) and posterior piriform
      cortex (pPCx) during the course of the acquisition session, which consisted of
      six odor (conditioned stimulus)-footshock (unconditioned stimulus) pairings. In
      BLA, we observed a transient increase in amino acid concentrations following the
      first odor-shock pairing, after which concentrations returned to baseline levels
      or slightly below. In pPCx, transient increases were seen after each pairing and
      were also observed after the last odor-shock pairing, corresponding to the
      predicted times of anticipated trials. Furthermore, we observed that for the
      first pairing, the increase in BLA occurred earlier than the increase in pPCx.
      These data suggest that the amygdala is engaged early during acquisition and
      precedes the activation of the olfactory cortex, which is maintained until the
      end of the session. In addition, our data raise the challenging idea that the
      olfactory cortex might store certain aspects of fear conditioning related to the
      timing of the associations.

PMID- 19864294
TI  - Enhanced insulin sensitivity after acute exercise is not associated with changes
      in high-molecular weight adiponectin concentration in plasma.
AB  - BACKGROUND AND OBJECTIVE: The effect of exercise on the plasma concentration of
      high-molecular weight (HMW) adiponectin (i.e. the biologically active form of
      circulating adiponectin) and the possible role of HMW adiponectin in mediating
      the exercise-induced enhancement of insulin action are not known. The aim of this
      study was to evaluate the relationship between the post-exercise increase in
      insulin sensitivity and plasma HMW adiponectin concentration. DESIGN AND METHODS:
      We measured total and HMW adiponectin concentrations in plasma using an ELISA
      kit, and insulin sensitivity using the updated homeostasis model assessment of
      insulin sensitivity (HOMA2-IS) score in the basal, overnight fasted state, once
      approximately 12 h after a single bout of moderate-intensity endurance exercise
      and once after an equivalent period of rest, in 27 healthy men and women (age:
      29+/-1 years and body mass index: 24.7+/-0.8 kg/m(2)). RESULTS: The HOMA2-IS
      score was 18+/-7% greater after exercise than after rest (229+/-20 and 196+/-17
      respectively; P=0.006), whereas the concentrations of total adiponectin (7.8+/
      0.5 and 7.7+/-0.5 mg/l respectively; P=0.597) and HMW adiponectin (3.0+/-0.3 and
      3.0+/-0.3 mg/l respectively; P=0.625) were not different. The exercise-induced
      change in HOMA2-IS score was not related to changes in total and HMW adiponectin
      concentrations (P>0.3). CONCLUSIONS: Changes in HMW adiponectin concentration are
      not involved in the acute exercise-induced enhancement of insulin action.

PMID- 19864296
TI  - Sleep deprivation affects extinction but not acquisition memory in honeybees.
AB  - Sleep-like behavior has been studied in honeybees before, but the relationship
      between sleep and memory formation has not been explored. Here we describe a new
      approach to address the question if sleep in bees, like in other animals,
      improves memory consolidation. Restrained bees were observed by a web camera, and
      their antennal activities were used as indicators of sleep. We found that the
      bees sleep more during the dark phase of the day compared with the light phase.
      Sleep phases were characterized by two distinct patterns of antennal activities:
      symmetrical activity, more prominent during the dark phase; and asymmetrical
      activity, more common during the light phase. Sleep-deprived bees showed rebound
      the following day, confirming effective deprivation of sleep. After appetitive
      conditioning of the bees to various olfactory stimuli, we observed their sleep.
      Bees conditioned to odor with sugar reward showed lesser sleep compared with bees
      that were exposed to either reward alone or air alone. Next, we asked whether
      sleep deprivation affects memory consolidation. While sleep deprivation had no
      effect on retention scores after odor acquisition, retention for extinction
      learning was significantly reduced, indicating that consolidation of extinction
      memory but not acquisition memory was affected by sleep deprivation.

PMID- 19864297
TI  - Post-learning infusion of anisomycin into the anterior cingulate cortex impairs
      instrumental acquisition through an effect on reinforcer valuation.
AB  - The integrity of the rodent anterior cingulate cortex (ACC) is essential for
      various aspects of instrumental behavior, but it is not clear if the ACC is
      important for the acquisition of a simple instrumental response. Here, it was
      demonstrated that post-session infusions of anisomycin into the rat ACC
      completely prevented the acquisition of instrumental responding. The experimental
      use of post-session intracranial infusions of plasticity inhibitors is assumed to
      affect local consolidation of plasticity, but not behavioral task performance.
      However, in associative appetitive conditioning, post-session intracranial
      infusion of pharmaco-active compounds could actually interfere with subsequent
      task performance indirectly through retrospective effects on the valuation of
      ingested rewards. Thus, it was subsequently demonstrated that the intracranial
      infusion of anisomycin into the ACC after sucrose pellet consumption
      significantly reduced subsequent pellet consumption, suggesting that the infusion
      of anisomycin into the ACC produced conditioned taste avoidance. In the third
      experiment, an innovative procedure was introduced that dissociated the effects
      of intracranial infusions after conditioning sessions on task-learning and
      unconditioned stimulus valuation. With this procedure, the infusion of anisomycin
      into the ACC after instrumental sessions did not affect instrumental reinforcer
      valuation or the acquisition of instrumental responding, suggesting that
      plasticity in the ACC is not necessary for the acquisition of instrumental
      behavior.

PMID- 19864298
TI  - Wasted salts and wasted bodies: new insight into the role of claudin 7 in the
      kidney.

PMID- 19864299
TI  - Reductions in laminin beta2 mRNA translation are responsible for impaired IGFBP-5
      mediated mesangial cell migration in the presence of high glucose.
AB  - Insulin-like growth factor binding protein-5 (IGFBP-5) mediates mesangial cell
      migration through activation of cdc42, and laminin421 binding to alpha(6)beta(1)
      integrin (Berfield AK, Hansen KM, Abrass CK. Am J Physiol Cell Physiol 291: C589
      C599, 2006). Because glomerular expression of laminin beta(2) is reduced in
      diabetic rats (Abrass CK, Spicer D, Berfield AK, St. John PL, Abrahamson DR. Am J
      Pathol 151: 1131-1140, 1997), we directly examined the effect of hyperglycemia on
      mesangial cell migration and laminin beta2 expression. Migration mediated by
      IGFBP-5 is impaired in the presence of 25 mM glucose. This reduction in migration
      was found to result from a loss in mesangial cell synthesis of laminin421, and
      IGFBP-5-induced migration could be restored by replacing laminin421. Additional
      studies showed that there was selective reduction in mRNA translation of laminin
      beta2 in the presence of high glucose. Preserved synthesis of laminin beta1
      indicates that not all proteins are reduced by high glucose and confirms prior
      data showing that laminin411 cannot substitute for laminin421 in IGFBP-5-mediated
      migration. Given the importance of mesangial migration in the reparative response
      to diabetes-associated mesangiolysis, these findings provide new insights into
      abnormalities associated with diabetic nephropathy and the potential importance
      of differential control of protein translation in determination of alterations of
      protein expression.

PMID- 19864300
TI  - Reactive oxygen species generated by renal ischemia and reperfusion trigger
      protection against subsequent renal ischemia and reperfusion injury in mice.
AB  - Ischemic preconditioning by a single event of ischemia and reperfusion (SIRPC)
      dramatically protects renal function against ischemia and reperfusion (I/R)
      induced several weeks later. We recently reported that reactive oxygen species
      (ROS) and oxidative stress were sustained in a kidney that had functionally
      recovered from I/R injury, thus suggesting an association between SIRPC and ROS
      and oxidative stress. However, the role of ROS in SIRPC remains to be clearly
      elucidated. To assess the involvement of ROS in SIRPC, mice were subjected to
      SIRPC (30 min of bilateral renal ischemia and 8 days of reperfusion) and then
      exposed to I/R injury. Thirty minutes of bilateral renal ischemia in the non
      SIRPC mice resulted in a marked increase in plasma creatinine levels 4 and 24 h
      after reperfusion, which was not observed in the I/R in the SIRPC mice. SIRPC
      resulted in increases in the levels of kidney superoxide. Administrations of
      manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin [MnTMPyP; a cell-permeable
      superoxide dismutase (SOD) mimetic] and N-acetylcysteine (NAc; a ROS scavenger)
      to SIRPC mice blocked the SIRPC-induced increase in superoxide levels and removed
      approximately 48-64% of the functional protection of the SIRPC kidney.
      Additionally, these administrations significantly inhibited I/R-induced increases
      in superoxide formation, hydrogen peroxide production, and lipid peroxidation,
      along with the inhibition of I/R-induced reductions in the expression and
      activity of manganese SOD, copper-zinc SOD, and catalase. Furthermore,
      administrations of MnTMPyP or NAc inhibited the SIRPC-induced increase in
      inducible nitric oxide synthase expression but did not inhibit the SIRPC-induced
      increases in heat shock protein-25 expression. In conclusion, the renoprotection
      afforded by SIRPC was triggered by ROS generated by SIRPC.

PMID- 19864301
TI  - Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins
      into the proximal tubule microvilli.
AB  - Angiotensin II (ANG II) stimulates proximal tubule (PT) sodium and water
      reabsorption. We showed that treating rats acutely with the angiotensin
      converting enzyme inhibitor captopril decreases PT salt and water reabsorption
      and provokes rapid redistribution of the Na(+)/H(+) exchanger isoform 3 (NHE3),
      Na(+)/Pi cotransporter 2 (NaPi2), and associated proteins out of the microvilli.
      The aim of the present study was to determine whether acute ANG II infusion
      increases the abundance of PT NHE3, NaPi2, and associated proteins in the
      microvilli available for reabsorbing NaCl. Male Sprague-Dawley rats were infused
      with a dose of captopril (12 microg/min for 20 min) that increased PT flow rate
      approximately 20% with no change in blood pressure (BP) or glomerular filtration
      rate (GFR). When ANG II (20 ng x kg(-1) x min(-1) for 20 min) was added to the
      captopril infusate, PT volume flow rate returned to baseline without changing BP
      or GFR. After captopril, NHE3 was localized to the base of the microvilli and
      NaPi2 to subapical cytoplasmic vesicles; after 20 min ANG II, both NHE3 and NaPi2
      redistributed into the microvilli, assayed by confocal microscopy and density
      gradient fractionation. Additional PT proteins that redistributed into low
      density microvilli-enriched membranes in response to ANG II included myosin VI,
      DPPIV, NHERF-1, ezrin, megalin, vacuolar H(+)-ATPase, aminopeptidase N, and
      clathrin. In summary, in response to 20 min ANG II in the absence of a change in
      BP or GFR, multiple proteins traffic into the PT brush-border microvilli where
      they likely contribute to the rapid increase in PT salt and water reabsorption.

PMID- 19864302
TI  - Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src
      kinase-dependent tyrosine phosphorylation of NR2B.
AB  - Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB
      ligands in spinal pain-related neural plasticity has been identified. To test
      whether Src-family non-receptor tyrosine kinase-dependent glutamatergic N-methyl
      d-aspartate receptor (NMDAR) NR2B subunit phosphorylation underlies lumbosacral
      spinal EphBR activation to mediate cross-organ sensitization between the colon
      and the urethra, external urethra sphincter electromyogram activity evoked by
      pelvic nerve stimulation and protein expression in the lumbosacral (L6-S2) dorsal
      horn were studied before and after intracolonic mustard oil (MO) instillation. We
      found MO instillation produced colon-urethra reflex sensitization along with an
      upregulation of endogenous ephrinB2 expression as well as phosphorylation of EphB
      1/2, Src-family kinase, and NR2B tyrosine residues. Intrathecal immunoglobulin
      fusion protein of EphB1 and EphB2 as well as PP2 reversed the reflex
      sensitization and NR2B phosphorylation caused by MO. All these results suggest
      that EphBR-ephrinB interactions, which provoke Src-family kinase-dependent NMDAR
      NR2B phosphorylation at the lumbosacral spinal cord level, are involved in cross
      organ sensitization, contributing to the development of viscero-visceral referred
      pain between the bowel and the urethra.

PMID- 19864303
TI  - Differential vulnerabilities of urethral afferents in diabetes and discovery of a
      novel urethra-to-urethra reflex.
AB  - Urethral reflexes are important regulators of micturition, and impairment of
      urethral afferent neuronal function may disrupt coordinated bladder and urethral
      activity, thereby contributing to voiding dysfunction in lower urinary tract
      disorders. Chemical stimulation by intraurethral irritant solution perfusion was
      used to determine whether urethral afferent neuronal function is altered in
      diabetes mellitus (DM). Sprague-Dawley rats were studied 10 wk after
      streptozotocin injection to induce DM or vehicle alone. Escalating doses of
      capsaicin (0.1-30 microM) or acetic acid (0.01-1%; AA) were perfused
      intraurethrally while recording isovolumetric bladder activity, urethral
      perfusion pressure, and electromyography of the external urethral sphincter (EUS
      EMG). Some rats were additionally treated with alpha-bungarotoxin, hexamethonium,
      or bilateral transection of the sensory branches of the pudendal nerves (PudSNx).
      Intraurethral capsaicin inhibited bladder contractions in six out of seven
      control rats but not in any of six DM rats. Low-frequency oscillations (LFOs) of
      intraurethral pressure were observed in five out of six control rats with
      capsaicin-induced bladder inhibition. In contrast, intraurethral AA inhibited
      bladder contractions and enhanced tonic EUS-EMG activity in six out of six
      control and five out of six DM rats. LFOs occurred in four out of six control and
      three of five DM rats with AA-induced bladder inhibition. Chemically induced
      bladder inhibition and LFOs were not prevented by alpha-bungarotoxin but were
      eliminated by PudSNx and hexamethonium. Finally, LFOs were followed by phasic EUS
      activity. These findings show that DM affects urethral afferent neurons
      differentially, compromising those expressing TRPV1 receptors. Urethral smooth
      muscle LFOs are neurogenically mediated and induce EUS activity, revealing the
      existence of a hitherto undescribed reflex pathway: a smooth-to-striated muscle
      urethra-to-urethra reflex.

PMID- 19864304
TI  - Human glomerular endothelium: interplay among glucose, free fatty acids,
      angiotensin II, and oxidative stress.
AB  - Glomerular endothelial cells (GEC) are strategically situated within the
      capillary loop and adjacent to the glomerular mesangium. GEC serve as targets of
      metabolic, biochemical, and hemodynamic signals that regulate the glomerular
      microcirculation. Unequivocally, hyperglycemia, hypertension, and the local renin
      angiotensin system partake in the initiation and progression of diabetic
      nephropathy (DN). Whether free fatty acids (FFA) and reactive oxygen species
      (ROS) that have been associated with the endothelial dysfunction of diabetic
      macrovascular disease also contribute to DN is not known. Since endothelial cells
      from different organs and from different species may display different
      phenotypes, we employed human GEC to investigate the effect of high glucose (22.5
      mmol/l), FFA (800 micromol/l), and angiotensin II (ANG II; 10(-7) mol/l) on the
      genesis of ROS and their effects on endothelial nitric oxide synthase (eNOS),
      cyclooxygenase-2 (COX-2), and the synthesis of prostaglandins (PGs). We
      demonstrated that high glucose but not high FFA increased the expression of a
      dysfunctional eNOS as well as increased ROS from NADPH oxidase (100%) and likely
      from uncoupled eNOS. ANG II also induced ROS from NADPH oxidase. High glucose and
      ANG II upregulated (100%) COX-2 via ROS and significantly increased the synthesis
      of prostacyclin (PGI(2)) by 300%. In contrast, FFA did not upregulate COX-2 but
      increased PGI(2) (500%). These novel studies are the first in human GEC that
      characterize the differential role of FFA, hyperglycemia, and ANG II on the
      genesis of ROS, COX-2, and PGs and their interplay in the early stages of
      hyperglcyemia.

PMID- 19864305
TI  - Association between the ubiquitin carboxyl-terminal esterase L1 gene (UCHL1) S18Y
      variant and Parkinson's Disease: a HuGE review and meta-analysis.
AB  - The ubiquitin carboxyl-terminal esterase L1 gene, UCHL1, located on chromosome
      4p14, has been studied as a potential candidate gene for Parkinson's disease
      risk. The authors conducted a Human Genome Epidemiology review and meta-analysis
      of published case-control studies of the UCHL1 S18Y variant and Parkinson's
      disease in Asian and Caucasian samples. The meta-analysis of studies in
      populations of Asian ancestry showed a statistically significant association
      between the Y allele and reduced risk of Parkinson's disease under a recessive
      model (odds ratio (OR) for YY vs. SY + SS = 0.79, 95% confidence interval (CI):
      0.67, 0.94; P = 0.006). For a dominant model, the association was not significant
      in Asian populations (OR for YY + SY vs. SS = 0.88, 95% CI: 0.68, 1.14; P =
      0.33). For populations of European ancestry, the meta-analysis showed a
      significant association between the Y allele and decreased risk of Parkinson's
      disease under a dominant model (OR = 0.89, 95% CI: 0.81, 0.98; P = 0.02) but not
      under a recessive model (OR = 0.92, 95% CI: 0.66, 1.30; P = 0.65). Using the
      Venice criteria, developed by the Human Genome Epidemiology Network Working Group
      on the assessment of cumulative evidence, the authors concluded that moderate
      evidence exists for an association between the S18Y variant and Parkinson's
      disease.

PMID- 19864306
TI  - Regulation of pentraxin-3 by antioxidants.
AB  - BACKGROUND: Pentraxin-3 (PTX3) may be a useful biomarker in sepsis, but its
      regulatory mechanisms are still unclear. Oxidative stress is well defined in
      patients with sepsis and has a role in regulation of inflammatory pathways which
      may include PTX3. We undertook an in vitro study of the effect of antioxidants on
      regulation of PTX3 in endothelial cells combined with a prospective observational
      pilot study of PTX3 in relation to markers of antioxidant capacity and oxidative
      stress in patients with sepsis. METHODS: Human endothelial cells were cultured
      with lipopolysaccharide 2 microg ml(-1), peptidoglycan G 20 microg ml(-1), tumour
      necrosis factor (TNF) alpha 10 ng ml(-1), interleukin-1 (IL-1) beta 20 ng ml(-1),
      or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM,
      trolox 100 mM, or idebenone 1 microM. Plasma samples were obtained from 15
      patients with sepsis and 11 healthy volunteers. RESULTS: PTX3 levels in plasma
      were higher in patients with sepsis than in healthy people [26 (1-202) ng ml(-1)
      compared with 6 (1-12) ng ml(-1), P=0.01]. Antioxidant capacity was lower in
      patients with sepsis than healthy controls [0.99 (0.1-1.7) mM compared with 2.2
      (1.3-3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were
      3.32 (0.3-10.6) nM and undetectable in controls. We found no relationship between
      PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3
      increased with all inflammatory stimulants but was highest in cells treated with
      TNFalpha plus IL-1beta. PTX3 concentrations were lower in cells co-treated with
      antioxidants (all P<0.05), associated with lower nuclear factor kappaB expression
      for NAC and trolox (P<0.05). CONCLUSIONS: PTX3 expression is down-regulated in
      vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to
      be unrelated to markers of oxidant stress or antioxidant capacity.

PMID- 19864307
TI  - Comparison of a supra-sternal cardiac output monitor (USCOM) with the pulmonary
      artery catheter.
AB  - BACKGROUND: Cardiac output (CO) cannot reliably be estimated by clinical
      examination. We aimed to measure the agreement between CO measurements using a
      supra-sternal Doppler monitor (USCOM, Coffs Harbour, Australia) and the pulmonary
      artery catheter (PAC). METHODS: The study was conducted in the intensive care
      unit of a tertiary teaching hospital. All patients with PAC in situ were
      eligible. Simultaneous CO readings were taken when clinically indicated.
      Investigators and clinicians were blinded to each other's results. The CO values
      used were the mean of three consecutive supra-sternal Doppler readings for
      patients with a sinus rhythm and seven for atrial fibrillation, and the mean of
      three thermodilution curves with acceptable form and values within 10% of each
      other for the PAC. Agreement was measured using both the paired t-test to
      calculate bias and limits of agreement and the intraclass correlation (ICC)
      coefficient. RESULTS: Ninety-four subjects were enrolled. From 89 subjects, 250
      paired comparisons were obtained. USCOM monitor readings were unobtainable in
      five patients. Mean supra-sternal Doppler CO was 5.5 litre min(-1). Bias was 
      0.09 litre min(-1) and levels of agreement were +/- 2.92 litre min(-1) when
      compared with PAC. ICC was 0.46 (95% CI 0.36-0.56), and mean percentage
      difference was 19 (IQR 6-31)%. CONCLUSIONS: In our subjects, there was poor
      agreement between CO measurements done with the supra-sternal Doppler monitor and
      PAC.

PMID- 19864308
TI  - Effects of maintaining a remifentanil infusion on the recovery profiles during
      emergence from anaesthesia and tracheal extubation.
AB  - BACKGROUND: Emergence from anaesthesia and tracheal extubation can be associated
      with hyperdynamic circulatory responses. We examined the effects of maintaining a
      remifentanil infusion on recovery profiles such as coughing and cardiovascular
      responses after general anaesthesia. METHODS: Forty patients undergoing
      endoscopic sinus surgery under general anaesthesia using total i.v. anaesthesia
      (propofol and remifentanil) were randomly allocated to a control group (n=20) or
      remifentanil group (n=20) during emergence from anaesthesia. At the end of
      surgery, propofol was ceased and the infusion of remifentanil was stopped in the
      control group and maintained in the remifentanil group at a target organ
      concentration of 1.5 ng ml(-1) until extubation. Heart rate (HR), mean arterial
      pressure (MAP), and recovery profiles were measured and evaluated. RESULTS: There
      was no significant difference in sex ratio, age, weight, height, time to eye
      opening, time to extubation, nausea, visual analogue scale, and time to
      discharge. Increases in HR and MAP occurred during emergence in the control group
      compared with baseline values. Increases in HR were attenuated in the
      remifentanil group and MAP decreased during recovery compared with baseline
      values. HR and MAP values were significantly higher in the control group [103
      (23) beats min(-1), 129 (17) mm Hg] compared with the remifentanil group [79 (17)
      beats min(-1), 112 (15) mm Hg] during emergence and tracheal extubation. Moderate
      or severe coughing was observed only in the control group (8/20 vs 0/20,
      P<0.001). CONCLUSIONS: Maintaining a remifentanil infusion reduced haemodynamic
      changes and coughing associated with tracheal extubation almost without
      significantly delaying recovery from anaesthesia.

PMID- 19864309
TI  - Do gender differences exist in pacemaker implantation?--results of an obligatory
      external quality control program.
AB  - AIMS: The aim of the study was to evaluate the effects of patient gender onto
      primary pacemaker implantation, evaluating the database of the Institute of
      Quality Assurance Hessen in the federal state of Hessen, Germany. METHODS AND
      RESULTS: The database of the obligatory external quality control program for the
      years 2003-2006 was evaluated retrospectively. In 72 centres, 17 826 patients
      undergoing stationary primary pacemaker implantation have been registered. Male
      patients had more AV blocks when compared with women and less sick sinus syndrome
      and atrial fibrillation with bradycardia. In patients being 80 years and older,
      men received significantly more dual-chamber devices than women for the
      indications: AV block and sick sinus syndrome. In women, atrial pacing thresholds
      were significantly higher and P-wave amplitudes were significantly lower. Women
      had, independent from age or pacing system implanted, significantly more acute
      complications than men, with significant differences for pneumothorax and pocket
      haematoma. CONCLUSION: This large-scale real-life patient cohort of primary
      stationary pacemaker implantation showed that gender has an impact onto pacemaker
      implantation, with less favourable outcomes for women.

PMID- 19864310
TI  - QRS alternans during idiopathic ventricular tachycardia originating from the
      right coronary cusp of the aorta.
AB  - A 77-year-old man underwent electrophysiological testing for idiopathic
      ventricular tachycardia (VT) with QRS alternans exhibiting a left bundle branch
      block and left inferior axis QRS morphology. Successful radiofrequency catheter
      ablation was achieved at the site of the earliest ventricular activation in the
      right coronary cusp. Pacing at this site reproduced an excellent pace map with
      QRS alternans. Pacing from other sites in the ventricular outflow tracts
      reproduced neither an excellent pace map nor QRS alternans. This case
      demonstrates that VT with a single origin and multiple exits in the aortic root
      may exhibit QRS alternans.

PMID- 19864311
TI  - Incidence of paroxysmal atrial tachycardias in patients treated with cardiac
      resynchronization therapy and continuously monitored by device diagnostics.
AB  - AIMS: Little is known about the incidence of paroxysmal atrial tachycardias (PAT)
      in patients with heart failure (HF). The availability of cardiac
      resynchronization therapy (CRT) devices with extended diagnostics for AT enables
      continuous monitoring of PAT episodes. The aim of the study was to assess the
      incidence over time of PAT in HF patients treated with CRT. METHODS AND RESULTS:
      Consecutive patients in NYHA functional class III or IV despite optimal drug
      therapy, QRS duration > or = 130 ms, left ventricular ejection fraction < or =
      35%, and left ventricular end-diastolic dimension > or = 55 mm were eligible for
      enrolment. Patients with permanent or persistent atrial fibrillation (AF) were
      not included in the study. The first follow-up examination was performed 2 weeks
      after implantation, to optimize atrial sensing and CRT. Subsequent follow-up
      examinations were carried out 15 and 28 weeks after implantation, to collect the
      telemetric data. A total of 173 patients (67 +/- 11 years, M 116) were enrolled.
      Complete arrhythmia monitoring data were available from 120 patients over a mean
      follow-up of 183 +/- 23 days. Atrial tachycardia episodes were detected through
      telemetry in 25 of 120 patients (21%) during at least one follow-up examination.
      Atrial tachycardia episodes were recorded in 29 and 17% (P = NS) of patients with
      and without previous history of AF, respectively. CONCLUSION: More than 20% of
      the overall HF patient population treated with CRT suffer PAT episodes.
      Paroxysmal atrial tachycardia may interfere with response to CRT. Therefore,
      telemetric data may be relevant to drive the appropriate therapy in each patient.

PMID- 19864312
TI  - Ventricular arrhythmia in coronary artery disease: limits of a risk
      stratification strategy based on the ejection fraction alone and impact of
      infarct localization.
AB  - AIMS: Estimates of the left ventricular ejection fraction (LVEF) in patients with
      life-threatening ventricular arrhythmias related to coronary artery disease (CAD)
      have rarely been reported despite it has become the basis for determining
      patient's eligibility for prophylactic defibrillator. We aimed to determine the
      extent and distribution of reduced LVEF in patients with sustained ventricular
      tachycardia or ventricular fibrillation. METHODS AND RESULTS: 252 patients
      admitted for ventricular arrhythmia related to CAD were included: 149 had acute
      myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive
      CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients
      had an old MI without residual ischaemia (Group III, 19%). 34% of the patients
      with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF
      evaluation, it can be estimated that less than one quarter of the whole study
      population had a known chronic MI with severely reduced LVEF. In Group III, the
      proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%;
      absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001),
      though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P =
      0.0499). CONCLUSION: Patients included in defibrillator trials represent only a
      minority of the patients at risk of sudden cardiac death. By applying the current
      risk stratification strategy based on LVEF, more than one third of the patients
      with old MI would not have qualified for a prophylactic defibrillator. Our study
      also suggests that inferior scars may be more prone to ventricular arrhythmia
      compared to anterior scars.

PMID- 19864313
TI  - Pseudo-atrial fibrillation due to non-reentrant AV nodal tachycardia.

PMID- 19864314
TI  - New candidate genes identified for controlling mouse gonadal sex determination
      and the early stages of granulosa and Sertoli cell differentiation.
AB  - Mammalian gonadal sex-determining (GSD) genes are expressed in a unique
      population of somatic cells that differentiate into granulosa cells in XX gonads
      or Sertoli cells in XY gonads. The ability to efficiently isolate these somatic
      support cells (SSCs) during the earliest stages of gonad development would
      facilitate identifying 1) new candidate GSD genes that may be involved in cases
      of unexplained abnormal gonad development and 2) genes involved in the earliest
      stages of granulosa and Sertoli cell differentiation. We report the development
      of a unique mouse carrying two transgenes that allow XX and XY mice to be
      distinguished as early as Embryonic Day 11.5 (E11.5) and allow SSCs to be
      isolated from undifferentiated (E11.5) and early differentiated (E12.5) fetal
      gonads. The Mouse Genome 430v2.0 GeneChip (Affymetrix) was used to identify
      transcripts exhibiting a sexual dimorphic expression pattern in XX and XY
      isolated SSCs. The analysis revealed previously unidentified sexually dimorphic
      transcripts, including low-level expressed genes such as Sry, a gene not
      identified in other microarray studies. Multigene real-time PCR analysis of 57
      genes verified that 53 were expressed in fetal gonads in a sexually dimorphic
      pattern, and whole-mount in situ hybridization analysis verified 4930563E18Rik,
      Pld1, and Sprr2d are expressed in XX gonads, and Fbln2, Ppargc1a, and Scrn1 are
      expressed in XY gonads. Taken together, the data provide a comprehensive resource
      for the spatial-temporal expression pattern of genes that are part of the genetic
      network underlying the early stages of mammalian fetal gonadal development,
      including the development of granulosa and Sertoli cells.

PMID- 19864315
TI  - Insulin-like growth factors and fish reproduction.
AB  - Knowledge of fish reproduction is of high relevance to basic fish biology and
      comparative evolution. Furthermore, fish are excellent biomedical models, and the
      impact of aquaculture on worldwide food production is steadily increasing.
      Consequently, research on fish reproduction and the potential modes of its
      manipulation has become more and more important. Reproduction in fish is
      regulated by the integration of endogenous neuroendocrine (gonadotropins),
      endocrine, and autocrine/paracrine signals with exogenous (environmental)
      factors. The main endocrine regulators of gonadal sex differentiation and
      function are steroid hormones. However, recent studies suggest that other
      hormones are also involved. Most prominent among these hormones are the insulin
      like growth factors (Igfs), i.e., Igf1, Igf2, and, most recently, Igf3. Thus, the
      present review deals with the expression patterns and potential physiological
      functions of Igf1 and Igf2 in male and female gonads. It further considers the
      potential involvement of growth hormone (Gh) and balances the reasons for
      endocrine vs. autocrine/paracrine action of the Igfs on the gonads of fish.
      Finally, this review discusses the early and late development of gonadal Igf1 and
      Igf2 and whether they are targets of endocrine-disrupting compounds. Future
      topics for novel research investigation on Igfs and fish reproduction are
      presented.

PMID- 19864316
TI  - Genomic profiling of microRNAs and messenger RNAs reveals hormonal regulation in
      microRNA expression in human endometrium.
AB  - MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate gene
      expression, have fundamental roles in biological processes, including cell
      differentiation and proliferation. These small molecules mainly direct either
      target messenger RNA (mRNA) degradation or translational repression, thereby
      functioning as gene silencers. Epithelial cells of the uterine lumen and glands
      undergo cyclic changes under the influence of the sex steroid hormones estradiol
      17beta and progesterone. Because the expression of miRNAs in human endometrium
      has been established, it is important to understand whether miRNAs have a
      physiological role in modulating the expression of hormonally induced genes. The
      studies herein establish concomitant differential miRNA and mRNA expression
      profiles of uterine epithelial cells purified from endometrial biopsy specimens
      in the late proliferative and midsecretory phases. Bioinformatics analysis of
      differentially expressed mRNAs revealed cell cycle regulation as the most
      significantly enriched pathway in the late proliferative-phase endometrial
      epithelium (P = 5.7 x 10(-15)). In addition, the WNT signaling pathway was
      enriched in the proliferative phase. The 12 miRNAs (MIR29B, MIR29C, MIR30B,
      MIR30D, MIR31, MIR193A-3P, MIR203, MIR204, MIR200C, MIR210, MIR582-5P, and
      MIR345) whose expression was significantly up-regulated in the midsecretory-phase
      samples were predicted to target many cell cycle genes. Consistent with the role
      of miRNAs in suppressing their target mRNA expression, the transcript abundance
      of predicted targets, including cyclins and cyclin-dependent kinases, as well as
      E2F3 (a known target of MIR210), was decreased. Thus, our findings suggest a role
      for miRNAs in down-regulating the expression of some cell cycle genes in the
      secretory-phase endometrial epithelium, thereby suppressing cell proliferation.

PMID- 19864317
TI  - Estrogen receptor ESR1 is indispensable for the induction of persistent vaginal
      change by neonatal 5alpha-dihydrotestosterone exposure in mice.
AB  - Development of the reproductive organs can be strongly affected by the hormonal
      environment. In the mouse, exposure to estrogens and androgens during the
      critical developmental period induces estrogen-independent cell proliferation and
      differentiation in the adult vaginal epithelium, which often results in cancerous
      lesions later in life. In the present study, we assessed the contributions of
      estrogen receptor 1 (alpha) (ESR1) to the developmental effects of the
      nonaromatizable androgen 5alpha-dihydrotestosterone (DHT) on female mouse vagina
      and external genitalia. The vagina of Esr1(-/-) mice treated neonatally with DHT
      showed atrophic epithelium, whereas the vaginal epithelium of Esr1(+/+) mice was
      stratified and keratinized even after ovariectomy. In addition, neonatal
      treatment with DHT led to persistent phosphorylation of ESR1 in the vaginae of 60
      day-old ovariectomized mice. We infer from these data that ESR1 is obligatory for
      the induction and maintenance of persistent vaginal epithelial changes induced by
      neonatal administration of DHT. Neonatal DHT treatment also induced hypospadias
      in both Esr1(-/-) and Esr1(+/+) mice. In contrast, DHT-induced formation of an os
      penis-like large bone in the clitoris was found in Esr1(-/-) mice but not in
      Esr1(+/-) or Esr1(+/+) mice. These results shed light on mechanisms of the
      induction of developmental effects elicited by sex steroid hormones on the
      developing animals.

PMID- 19864318
TI  - Retinoblastoma 1 protein modulates XY germ cell entry into G1/G0 arrest during
      fetal development in mice.
AB  - During mouse germ cell development, the first sign of sex differentiation occurs
      when XY germ cells enter G(1)/G(0) arrest from 12.5 days postcoitum (dpc).
      Retinoblastoma 1 (RB1), a potent cell cycle regulator, was investigated in XY
      germ cell arrest by studying germ cell proliferation in Rb1(-/-) mutant mouse
      embryos. Because mice homozygous for the Rb1 deletion die in utero around 14.5
      dpc, we used ex vivo culture techniques to allow analysis of developing gonads to
      16.5 dpc. In Rb1(-/-) gonads, we observed normal somatic cell development,
      assessed by immunofluorescence for markers HSD3B1 and anti-Mullerian hormone.
      However, at 14.5 dpc, when wild-type XY germ cells had arrested, we could detect
      actively proliferating germ cells using the proliferation markers MKI67, pHH3,
      and bromodeoxyuridine incorporation. The increased proliferation was reflected
      with a trend of increased germ cell number and expression of germ cell markers
      Ddx4 and Pou5f1 in the Rb1(-/-) testes. By 16.5 dpc, this phenotype was resolved
      such that the entire germ cell population had entered G(1)/G(0) arrest, although
      the total germ cell number remained elevated. At each stage analyzed, we saw no
      increase in expression of RB1 family members Rbl1 and Rbl2 in the Rb1(-/-)
      testes, but we saw a significant increase of cyclin-dependent kinase (CDK)
      inhibitor Cdkn1b and Cdkn2b expression. We conclude that Rb1 is required for
      correct germ cell entry into G(1)/G(0) arrest in the wild-type gonad at 14.5 dpc,
      but in its absence, upregulation of other cell cycle suppressors, including
      Cdkn1b and Cdkn2b, can induce delayed germ cell arrest.

PMID- 19864320
TI  - Are children diagnosed with the combined form of ADHD pervasively hyperactive?
AB  - Diagnostic criteria specified by the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV-TR ; American Psychological Association [APA], 2000) require
      that motor excess be present across situations, at home and school, in order to
      establish that this condition is a characteristic of the child. The article
      discusses a study whose primary purpose was to use actigraphy to validate teacher
      and parent reports of hyperactivity at home and school. Continuous activity
      measurements were recorded for each minute of each 24-hr period (1,440
      measurements per child per day) for a full 7-day week, during school and at home,
      on 9 children clinically diagnosed with the combined form of ADHD and 9 control
      children clinically examined at the same community mental health clinic and
      determined not to meet diagnostic criteria. The article highlights that the
      children with ADHD had not yet started medication, and the study findings reveal
      that only 1 of 9 children diagnosed with the combined form of ADHD was measurably
      pervasively hyperactive as DSM-IV-TR inclusion criteria require. Implications are
      discussed.

PMID- 19864319
TI  - Application of a standardized assessment methodology within the context of an
      evidence-based treatment for substance abuse and its associated problems.
AB  - Administrators of community-based treatment programs are increasingly being
      required to utilize psychometrically validated instruments to measure the
      effectiveness of their interventions. However, developers of psychometric
      measures have often failed to report strategies relevant to the administration of
      these measures in nontraditional settings outside the therapy office. Moreover,
      with few exceptions, developers of evidence-based treatments (EBTs) have
      insufficiently disseminated methods for integrating assessment measures into
      treatment planning. Therefore, the purpose of this article is to review an
      assessment methodology that may be utilized to support EBT for individuals who
      are identified for substance abuse or related problem behaviors. The application
      of this methodology is demonstrated utilizing Family Behavior Therapy to
      exemplify "real world" scenarios involving adolescents and adults. Although many
      of these strategies are evidence supported, most are based on clinical
      experiences occurring in clinical trials and dissemination efforts within
      community settings.

PMID- 19864321
TI  - Identifying stimuli that alter immediate and subsequent levels of vocal
      stereotypy: a further analysis of functionally matched stimulation.
AB  - We used a three-component multiple-schedule with a brief reversal design to
      evaluate the effects of structurally unmatched and matched stimuli on immediate
      and subsequent vocal stereotypy that was displayed by three children with autism
      spectrum disorders. For 2 of the 3 participants, access to matched stimuli,
      unmatched stimuli, and music decreased immediate levels of vocal stereotypy;
      however, with the exception of matched stimuli for one participant, none of the
      stimuli produced a clear abolishing operation for subsequent vocal stereotypy.
      That is, vocal stereotypy typically increased to baseline levels shortly after
      alternative stimulation was removed. Detection of motivating operations for each
      participant's vocal stereotypy was aided by the analysis of component
      distributions. The results are discussed in terms of immediate and subsequent
      effects of preferred stimuli on automatically reinforced problem behavior.

PMID- 19864322
TI  - Phorbol 12-myristate 13-acetate-induced endocytosis of the Na-K-2Cl cotransporter
      in MDCK cells is associated with a clathrin-dependent pathway.
AB  - In secretory epithelial cells, the basolateral Na(+)-K(+)-2Cl(-) cotransporter
      (NKCC1) plays a major role in salt and fluid secretion. Our laboratory has
      identified NKCC1 surface expression as an important regulatory mechanism for Cl(
      ) secretion in the colonic crypt cell line T84, a process also present in native
      human colonic crypts. We previously showed that activation of protein kinase C
      (PKC) by carbachol and phorbol 12-myristate 13-acetate (PMA) decreases NKCC1
      surface expression in T84 cells. However, the specific endocytic entry pathway
      has not been defined. We used a Madin-Darby canine kidney (MDCK) cell line stably
      transfected with enhanced green fluorescent protein (EGFP)-NKCC1 to map NKCC1
      entry during PMA exposure. At given times, we fixed and stained the cells with
      specific markers (e.g., dynamin II, clathrin heavy chain, and caveolin-1). We
      also used chlorpromazine, methyl-beta-cyclodextrin, amiloride, and dynasore,
      blockers of the clathrin, caveolin, and macropinocytosis pathways and the vesicle
      "pinchase" dynamin, respectively. We found that PMA caused dose- and time
      dependent NKCC1 endocytosis. After 2.5 min of PMA exposure, approximately 80% of
      EGFP-NKCC1 endocytic vesicles colocalized with clathrin and approximately 40%
      colocalized with dynamin II and with the transferrin receptor, the uptake of
      which is also mediated by clathrin-coated vesicles. We did not observe
      significant colocalization of EGFP-NKCC1 endocytic vesicles with caveolin-1, a
      marker of the caveolae-mediated endocytic pathway. We quantified the effect of
      each inhibitor on PMA-induced EGFP-NKCC1 endocytosis and found that only
      chlorpromazine and dynasore caused significant inhibition compared with the
      untreated control (61% and 25%, respectively, at 2.5 min). Together, these
      results strongly support the conclusion that PMA-stimulated NKCC1 endocytosis is
      associated with a clathrin pathway.

PMID- 19864323
TI  - FOXO signaling is required for disuse muscle atrophy and is directly regulated by
      Hsp70.
AB  - The purpose of the current study was to determine whether heat shock protein 70
      (Hsp70) directly regulates forkhead box O (FOXO) signaling in skeletal muscle.
      This aim stems from previous work demonstrating that Hsp70 overexpression
      inhibits disuse-induced FOXO transactivation and prevents muscle fiber atrophy.
      However, although FOXO is sufficient to cause muscle wasting, no data currently
      exist on the requirement of FOXO signaling in the progression of physiological
      muscle wasting, in vivo. In the current study we show that specific inhibition of
      FOXO, via expression of a dominant-negative FOXO3a, in rat soleus muscle during
      disuse prevented >40% of muscle fiber atrophy, demonstrating that FOXO signaling
      is required for disuse muscle atrophy. Subsequent experiments determined whether
      Hsp70 directly regulates FOXO3a signaling when independently activated in
      skeletal muscle, via transfection of FOXO3a. We show that Hsp70 inhibits FOXO3a
      dependent transcription in a gene-specific manner. Specifically, Hsp70 inhibited
      FOXO3a-induced promoter activation of atrogin-1, but not MuRF1. Further studies
      showed that a FOXO3a DNA-binding mutant can activate MuRF1, but not atrogin-1,
      suggesting that FOXO3a activates these two genes through differential mechanisms.
      In summary, FOXO signaling is required for physiological muscle atrophy and is
      directly inhibited by Hsp70.

PMID- 19864324
TI  - Anionic leak currents through the Na+/monocarboxylate cotransporter SMCT1.
AB  - SMCT1 is a Na-coupled cotransporter of short chain monocarboxylates, which is
      expressed in the apical membrane of diverse epithelia such as colon, renal
      cortex, and thyroid. We previously reported that SMCT1 cotransport was reduced by
      extracellular Cl(-) replacement with cyclamate(-) and that the protein exhibited
      an ostensible anionic leak current. In this paper, we have revisited the
      interaction between small monovalent anions and SMCT cotransport and leak
      currents. We found that the apparent Cl(-) dependence of cotransport was due to
      inhibition of this protein by the replacement anion cyclamate, whereas several
      other replacement anions function as substrates for SMCT1; a suitable replacement
      anion (MES(-)) was identified. The observed outward leak currents represented
      anionic influx and favored larger anions (NO(3)(-)>I(-)>Br(-)>Cl(-)); currents in
      excess of 1 muA (at +50 mV) could be observed and exhibited a quasilinear
      relationship with anion concentrations up to 100 mM. Application of 25 mM
      bicarbonate did not produce measurable leak currents. The leak current displayed
      outward rectification, which disappeared when external Na(+) was replaced by N
      methyl-d-glucamine(+). More precisely, external Na(+) blocked the leak current in
      both directions, but its K(i) value rose rapidly when membrane potential became
      positive. Thus SMCT1 possesses a anionic leak current that becomes significant
      whenever external Na(+) concentration is reduced. The presence of this leak
      current may represent a second function for SMCT1 in addition to cotransporting
      short chain fatty acids, and future experiments will determine whether this
      function serves a physiological role in tissues where SMCT1 is expressed.

PMID- 19864325
TI  - Epidermal growth factor increases lysophosphatidic acid production in human
      ovarian cancer cells: roles for phospholipase D2 and receptor transactivation.
AB  - Lysophosphatidic acid (LPA), is a lipid mediator that binds to G-protein coupled
      receptors. Epidermal growth factor (EGF), a polypeptide growth factor, binds to
      the EGF receptor (EGFR), a receptor tyrosine kinase. Both LPA and EGF induce
      responses in tumor cells that include proliferation, migration, metastasis, and
      induction of angiogenesis. LPA has the potential to act as an autocrine/paracrine
      factor and can transactivate the EGFR. This study explores the role of
      phospholipase D2 (PLD2) activation in LPA production, as well as cross-talk
      between EGF and LPA receptors. We demonstrate that EGF and LPA both stimulate
      production of LPA by OVCAR3 and SKOV3 human ovarian cancer cell lines. PD158780,
      an EGFR-selective tyrosine kinase inhibitor, blocks LPA production in response to
      both EGF and LPA in OVCAR3 and SKOV3 cells. Pertussis toxin, an inhibitor of LPA
      receptor signaling, inhibits LPA production in response to both EGF and LPA.
      Similar results were observed for the LPA receptor antagonist, Ki16425.
      Overexpression of PLD2 increases LPA production, while knockdown of PLD2 blocks
      EGF-induced LPA production. A phospholipase A2 (PLA2) inhibitor also blocks LPA-
      and EGF-induced LPA production. These results indicate that EGF stimulates LPA
      production in a manner that requires PLD2, and suggest that cross-talk can occur
      bidirectionally between EGF and LPA receptors.

PMID- 19864326
TI  - Distribution of some natural and man-made radionuclides in soil from the city of
      Veles (Republic of Macedonia) and its environs.
AB  - A systematic study of soil radioactivity in the metallurgical centre of the
      Republic of Macedonia, the city of Veles and its environs, was carried out. The
      measurement of the radioactivity was performed in 55 samples from evenly
      distributed sampling sites. The gross alpha and gross beta radioactivity
      measurements were made as a screening, using a low background gas-flow
      proportional counter. For the analysis of (40)K, (238)U, (232)Th and (137)Cs, a P
      type coaxial high purity germanium detector was used. The values for the activity
      concentrations of the natural radionuclides fall well within the worldwide range
      as reported in the literature. It is shown that the activity of man-made
      radionuclides, except for (137)Cs, is below the detection limit. (137)Cs
      originated from the atmospheric deposition and present in soil in the activity
      concentration range of 2-358 Bq kg(-1) is irregularly distributed over the
      sampled territory owing to the complicated orography of the land. The results of
      gamma spectrometry are compared to the K, U, and Th concentrations previously
      obtained by the reactor neutron activation analysis in the same soil samples.

PMID- 19864327
TI  - The development of a guidance level for patient dose for CT examinations in
      Korea.
AB  - The primary goal of this study was to analyse the state of patient doses in the
      field of computed tomography (CT) examinations in the Republic of Korea. All
      survey data including the CT applications and patient dose details were obtained
      from general hospitals registered in the Korean Hospital Association. The
      systematic analysis of the patient dose survey gives target values of the
      weighted computed tomography dose index (CTDI(w)) and the dose-length product
      (DLP). The targeted CTDI(w) values were 69, 69, 31, 19, 44, 25, 24, 20, 2, 19 and
      19 mGy for the brain non-contrast enhancement (BNCE), brain contrast enhancement
      (BCE), neck, chest, spine, liver, pancreas, stomach, kidneys, abdomen routine and
      abdomen trauma protocols, respectively. The targeted DLP values were 1056, 2112,
      762, 1234, 1338, 2794, 2742, 2378, 2836, 1844 and 1939 mGy cm for the BNCE, BCE,
      neck, chest, spine, liver, pancreas, stomach, kidneys, abdomen routine and
      abdomen trauma protocols, respectively. Comparing with the EUR recommendation,
      especially in the DLP, the adjustment of the total scan phase frequency and the
      shortening of the scan phase in each scan phase are needed to reduce the patients
      radiation exposure to international standards.

PMID- 19864328
TI  - Estimation of skin entrance doses (SEDs) for common medical X-ray diagnostic
      examinations in India and proposed diagnostic reference levels (DRLs).
AB  - Skin entrance doses (SEDs) were estimated by carrying out measurements of air
      kerma from 101 X-ray machines installed in 45 major and selected hospitals in the
      country by using a silicon detector-based dose Test-O-Meter. 1209 number of air
      kerma measurements of diagnostic projections for adults have been analysed for
      seven types of common diagnostic examinations, viz. chest (AP, PA, LAT), lumbar
      spine (AP, LAT), thoracic spine (AP, LAT), abdomen (AP), pelvis (AP), hip joints
      (AP) and skull (PA, LAT) for different film-screen combinations. The values of
      estimated diagnostic reference levels (DRLs) (third quartile values of SEDs) were
      compared with guidance levels/DRLs of doses published by the IAEA-BSS-Safety
      Series No. 115, 1996; HPA (NRPB) (2000 and 2005), UK; CRCPD/CDRH (USA), European
      Commission and other national values. The values of DRLs obtained in this study
      are comparable with the values published by the IAEA-BSS-115 (1996); HPA (NRPB)
      (2000 and 2005) UK; EC and CRCPD/CDRH, USA including values obtained in previous
      studies in India.

PMID- 19864329
TI  - Influence of a cement industry on the fine and ultrafine particles composition in
      a rural area.
AB  - The cement industry of this work is located in the Fumane valley, in the north of
      Verona. The environmental impact of the air emissions from the plant was studied
      using different methods: the characterisation of the raw materials utilised in
      the production process and of the emissions from the chimney of the clinker kiln;
      the sampling of the air particles on filter in the region around the plant; the
      biomonitoring using transplanted mosses; the study of the air pollution
      dispersion using a model.

PMID- 19864330
TI  - Development of an electrolysis system for tritium enrichment in superficial water
      samples.
AB  - Tritium present in the environment gradually decreased in the last decades and
      nowadays it has reached extremely low activity concentrations. The purpose of the
      present work is the implementation of a tritium enrichment system in water
      samples using electrolytic techniques and pure nickel and iron electrodes. In the
      present work a mean tritium enrichment factor of 13.0 +/- 3.2 was obtained. This
      result should allow to reach a minimum detectable activity of tritium in water
      samples of about 1 tritium unit (TU) or less. The present enrichment system
      necessitates further adjustments and improvements, such as a cooling system in
      order to reduce the tritium losses due to evaporation.

PMID- 19864331
TI  - Measurement of electromagnetic fields generated by air traffic control radar
      systems with spectrum analysers.
AB  - Air traffic control (ATC) primary radars are 'classical' radars that use echoes
      of radiofrequency (RF) pulses from aircraft to determine their position. High
      power RF pulses radiated from radar antennas may produce high electromagnetic
      field levels in the surrounding area. Measurement of electromagnetic fields
      produced by RF-pulsed radar by means of a swept-tuned spectrum analyser are
      investigated here. Measurements have been carried out both in the laboratory and
      in situ on signals generated by an ATC primary radar.

PMID- 19864332
TI  - Microscale modelling simulations for the site characterization of air quality
      stations in an urban environment.
AB  - The presence of natural or artificial barriers placed near the air quality
      measuring stations located in an urban environment poses some problems in the
      assessment of their siting and significance. The atmospheric flow distortion
      induced by these structures can create situations that affect the concentration
      levels of measured pollutants. A modelling study at microscale of the pollutant
      dispersion in an urban environment has been performed to quantify these possible
      effects on measurements. The target domain is located in a central section of the
      city of Turin (northern Italy) around via della Consolata, near the location of
      an existing station of the regional monitoring network. The study involved the
      use of the modelling system Micro-Swift-Spray, which takes into account the
      presence of complex topographical barriers, including street canyons and squares
      surrounded by buildings. Two entire days have been simulated, to characterise
      both a critical and a more standard condition, with reconstruction of average
      flow, turbulence and hourly ground-level pollutant concentrations. Contributions
      from both traffic and building-heating sources have been considered and a
      comparison with measured concentrations has been performed to verify the
      representativeness of the measuring station with respect to both average
      conditions and spatial variability inside the considered region, otherwise very
      difficult to asses through a single and isolated measuring point.

PMID- 19864333
TI  - Canadian province-level risk factor analysis of macrolide consumption patterns
      (2000-2006).
AB  - OBJECTIVES: To assess provincial-level predictors among socioeconomic and
      influenza rate data for the use of different macrolide antimicrobials in Canada
      from 2000 to 2006. METHODS: Multivariable models were developed to describe
      macrolide defined daily doses per capita. RESULTS: Use was highest during October
      to March for all macrolides. Investigated yearly and provincial patterns differed
      considerably among the macrolide agents. Associations with socioeconomic
      variables were similar between clarithromycin and erythromycin, while
      azithromycin consumption showed some differences in its association with these
      variables. Consistently, the rate of influenza was significantly associated with
      increased macrolide use. The influenza rate interacted with socioeconomic
      variables in some models; as the influenza rate increased, the greatest increase
      in demand for macrolides occurred in populations with high percentages of low
      income individuals, high unemployment levels and low percentages of individuals
      with bachelor's degrees. CONCLUSIONS: The impact of associations among macrolide
      consumption, influenza and socioeconomic factors may reflect inappropriate use of
      these agents to treat viral infections and/or prescribing for secondary
      infections, and knowledge of the virus versus bacteria problem and accessibility
      of healthcare. Further research surrounding differences in access to
      antimicrobial prescriptions and treatment options between advantaged and
      disadvantaged populations is suggested to further understand the dynamics of
      antimicrobial use in Canada.

PMID- 19864335
TI  - Evaluation of the lack of anorectic effect of intracerebroventricular insulin in
      rats.
AB  - Insulin detemir is a novel human insulin analog that does not show the usual
      propensity for weight gain in diabetic patients. We speculated that this
      beneficial effect could be due to insulin detemir exerting stronger anorectic
      effects within the brain than other insulins. To study the central effects of
      regular human insulin and insulin detemir on food intake, the present study was
      undertaken. We used acute intracerebroventricular insulin injections to compare
      food intake and body weight in rats fed ad libitum. Contrary to previously
      published data, we found that neither regular human insulin (8 or 32 mU) nor
      insulin detemir (1,290 pmol) reduced food intake in this model. Melanotan-II was
      also injected intracerebroventricularly as a positive control, and significantly
      reduced food intake and body weight, suggesting that our intracerebroventricular
      model is able to show anorectic effects. A series of experiments was therefore
      conducted in which different set-ups were tested to investigate which factors
      would be required to produce the reported anorectic effect of
      intracerebroventricular insulin. Although we varied rat strain, stereotactic
      coordinates, formulations of insulin and vehicle, dose, volume, and time of
      injection, the anorectic effect of intracerebroventricular insulin could not be
      replicated. Therefore, we suggest that acute intracerebroventricularly injected
      insulin does not robustly inhibit food intake in rats. Based on our results, the
      acute intracerebroventricular injection procedure may not be a preferred method
      for studying the central anorectic effects of insulin in rats. Instead,
      administrations over time or locally in hypothalamic nuclei might be recommended.

PMID- 19864334
TI  - The heme oxygenase system attenuates pancreatic lesions and improves insulin
      sensitivity and glucose metabolism in deoxycorticosterone acetate hypertension.
AB  - Recent clinical reports indicate that impaired glucose tolerance is a common
      phenomenon in primary aldosteronism. Aldosterone stimulates NF-kappaB and
      activating protein-1 (AP-1) to cause oxidative injury. Elevated oxidative stress
      impairs insulin signaling. We recently showed that the heme oxygenase (HO) system
      lowers blood pressure (BP) in deoxycorticosterone-acetate (DOCA)+salt
      hypertension, a model of primary aldosteronism. However, the effect of the HO
      system on insulin sensitivity in this model remains largely unclear. Here we
      report the effects of the HO-inducer hemin and the HO-blocker [chromium
      mesoporphyrin (CrMP)] on insulin sensitivity/glucose metabolism. Our experimental
      design included the following 10 groups: (A) controls [(i) surgery-free or normal
      Sprague-Dawley (SD), (ii) uninephrectomized (UnX)-sham, (iii) UnX+salt
      (0.9%NaCl+0.2%KCl) and (iv) UnX+DOCA]; (B) DOCA+salt; (C) hemin+DOCA+salt; (D)
      hemin+CrMP+DOCA+salt; (E) CrMP+DOCA+salt; (F) vehicle-treated rats and (G) normal
      SD+hemin. Hemin therapy lowered BP and increased plasma insulin and the insulin
      sensitizing protein adiponectin with slight but significant reduction of
      glycemia, while CrMP abolished the hemin effects. Furthermore, hemin improved
      intraperitoneal glucose and insulin tolerance, suggesting that although DOCA+salt
      hypertensive rats were normoglycemic, insulin signaling may be impaired. In
      contrast, the HO-inhibitor CrMP aggravated insulin resistance and exacerbated
      glucose and insulin tolerance. Interestingly, the enhanced insulin sensitization
      in hemin-treated animals was accompanied by reduced urinary/gastrocnemius muscle
      8-iso-prostaglandin F(2alpha) (8-isoprostane), inflammatory/oxidative
      transcription factors like NF-kappaB, AP-1, JNK, and heme content, whereas HO-1,
      HO-activity, cGMP, and plasma/gastrocnemius muscle antioxidants including
      bilirubin, ferritin, SOD, catalase, and the total antioxidant capacity were
      increased. Similarly, hemin enhanced pancreatic HO, cGMP, and cAMP but suppressed
      8-isoprostane and attenuated pancreatic histopathological lesions including
      fibrosis, interstitial edema, acinar cell necrosis, vacuolization, and
      mononuclear cell infiltration, with corresponding improvement of insulin
      production. Our results suggest that impaired insulin signaling may be a
      forerunner to hyperglycemia in aldosteronism. By preserving pancreatic
      morphology, potentiating insulin signaling, and lowering BP, the HO system may
      prevent metabolic and cardiovascular complications in aldosteronism.

PMID- 19864336
TI  - Sex-related decrease in [Ca2+]i signaling and Ca2+-dependent contraction in
      inferior vena cava of female rat.
AB  - Sex differences in the incidence of varicose veins have been suggested; however,
      the venous mechanisms involved are unclear. We hypothesized sex-related
      differences in venous function and underlying distinctions in intracellular free
      calcium, [Ca(2+)](i), signaling and Ca(2+)-dependent mechanisms of venous
      contraction. Circular segments of inferior vena cava (IVC) from male and female
      Sprague-Dawley rats were suspended between two hooks, labeled with fura-2, and
      placed in a cuvet inside a spectrofluorometer for simultaneous measurement of
      isometric contraction and the 340/380 fluorescence ratio (indicative of
      [Ca(2+)](i)). In male IVC, phenylephrine (PHE; 10(-5) M) caused significant
      increase in contraction and [Ca(2+)](i). In female IVC, PHE-induced contraction
      was significantly reduced, but [Ca(2+)](i) did not differ significantly from
      males. Membrane depolarization by KCl (96 mM), which stimulates Ca(2+) influx,
      caused parallel increases in contraction and [Ca(2+)](i) in male IVC, and the KCl
      induced contraction was significantly reduced in parallel with [Ca(2+)](i) in
      female IVC. In male IVC stimulated with 0 Ca(2+) KCl solution, the addition of
      increasing concentrations of extracellular Ca(2+) ([Ca(2+)](e)) (0.1, 0.3, 0.6,
      1, and 2.5 mM) caused stepwise increases in contraction and [Ca(2+)](i), and both
      the KCl-induced [Ca(2+)](e)-contraction curve and the [Ca(2+)](e)-[Ca(2+)](i)
      curve were reduced in female IVC, suggesting reduced Ca(2+) entry via voltage
      gated channels. The PHE-induced [Ca(2+)](e)-contraction curve was significantly
      reduced in females, but the [Ca(2+)](e)-[Ca(2+)](i) curve was similar in female
      and male IVC, suggesting the involvement of other mechanisms in addition to
      Ca(2+) entry. The [Ca(2+)](e)-contraction and [Ca(2+)](e)-[Ca(2+)](i) curves were
      used to construct the [Ca(2+)](i)-contraction relationship. The KCl-induced
      [Ca(2+)](i)-contraction relationship was superimposed in male and female IVC. In
      contrast, the PHE-induced [Ca(2+)](i)-contraction relationship was reduced and
      located to the right in female compared with male IVC, suggesting reduced
      [Ca(2+)](i) sensitivity of the venous contractile myofilaments. The reduced
      contraction, [Ca(2+)](i), and [Ca(2+)](i) sensitivity in female veins render them
      more prone to dilation. These sex-specific reductions in venous function, if they
      also occur in human veins, may play a role in the greater incidence of varicose
      veins in females.

PMID- 19864337
TI  - Effects of environmental hypoxia on cardiac energy metabolism and performance in
      tilapia.
AB  - The ability of an animal to depress ATP turnover while maintaining metabolic
      energy balance is important for survival during hypoxia. In the present study, we
      investigated the responses of cardiac energy metabolism and performance in the
      hypoxia-tolerant tilapia (Oreochromis hybrid sp.) during exposure to
      environmental hypoxia. Exposure to graded hypoxia (> or =92% to 2.5% air
      saturation over 3.6 +/- 0.2 h) followed by exposure to 5% air saturation for 8 h
      caused a depression of whole animal oxygen consumption rate that was accompanied
      by parallel decreases in heart rate, cardiac output, and cardiac power output
      (CPO, analogous to ATP demand of the heart). These cardiac parameters remained
      depressed by 50-60% compared with normoxic values throughout the 8-h exposure.
      During a 24-h exposure to 5% air saturation, cardiac ATP concentration was
      unchanged compared with normoxia and anaerobic glycolysis contributed to ATP
      supply as evidenced by considerable accumulation of lactate in the heart and
      plasma. Reductions in the provision of aerobic substrates were apparent from a
      large and rapid (in <1 h) decrease in plasma nonesterified fatty acids
      concentration and a modest decrease in activity of pyruvate dehydrogenase.
      Depression of cardiac ATP demand via bradycardia and an associated decrease in
      CPO appears to be an integral component of hypoxia-induced metabolic rate
      depression in tilapia and likely contributes to hypoxic survival.

PMID- 19864338
TI  - Edelman's equation is valid in acute hyponatremia in a porcine model: plasma
      sodium concentration is determined by external balances of water and cations.
AB  - Acute hyponatremia is a serious condition, which poses major challenges. Of
      particular importance is what determines plasma sodium concentration ([Na(+)]).
      Edelman introduced an explicit model to describe plasma [Na(+)] in a population
      as [Na(+)] = alpha.(exchangeable Na(+) + exchangeable K(+))/(total body water) -
      beta. Evidence for the clinical utility of the model in the individual and in
      acute hyponatremia is sparse. We, therefore, investigated how the measured plasma
      [Na(+)] could be predicted in a porcine model of hyponatremia. Plasma [Na(+)] was
      estimated from in vivo-determined balances of water, Na(+), and K(+), according
      to Edelman's equation. Acute hyponatremia was induced with desmopressin acetate
      and infusion of a 2.5% glucose solution in anesthetized pigs. During 480 min,
      plasma [Na(+)] and osmolality were reduced from 136 (SD 2) to 120 mmol/l (SD 3)
      and from 284 (SD 4) to 252 mosmol/kgH(2)O (SD 5), respectively. The following
      interpretations were made. First, Edelman's model, which, besides dilution, takes
      into account Na(+) and K(+), fits plasma [Na(+)] significantly better than
      dilution alone. Second, a common value of alpha = 1.33 (SD 0.08) and beta = 
      13.04 mmol/l (SD 7.68) for all pigs explains well the plasma [Na(+)] in the
      individual animal. Third, measured exchangeable Na(+) and calculated exchangeable
      Na(+) + K(+) per weight in the pigs are close to Edelman's findings in humans,
      whereby the methods are cross-validated. In conclusion, plasma [Na(+)] can be
      explained in the individual animal by external balances, according to Edelman's
      construct in acute hyponatremia.

PMID- 19864340
TI  - Pretreatment with a soluble activin type IIB receptor/Fc fusion protein improves
      hypoxia-induced muscle dysfunction.
AB  - Hypoxia, or reduced oxygen, occurs in a variety of clinical and environmental
      situations. Hypoxic exposure is associated with decreased muscle mass and a
      concomitant reduction in exercise capacity, although the exact mechanisms are not
      completely understood. The activin type IIB receptor (ActRIIB) is a receptor for
      transforming growth factor-beta (TGFbeta) superfamily members that are involved
      in the negative regulation of lean tissue mass. Given that hypoxia has negative
      effects on muscle mass and function and that modulation of the ActRIIB has been
      shown to increase muscle mass, we tested the hypothesis that pharmacological
      targeting of the ActRIIB for 2 wk would attenuate the loss of muscle mass and
      function in mice after exposure to normobaric hypoxia. ActRIIB modulation was
      achieved using a soluble activin receptor/Fc fusion protein (sActRIIB) in mice
      housed in a hypoxic chamber for 1 or 2 wk. Hypoxia induced a reduction in body
      weight in PBS- and sActRIIB-treated mice, although sActRIIB-treated mice remained
      larger throughout the hypoxic exposure. The absolute forces generated by extensor
      digitorum longus muscles were also significantly greater in sActRIIB- than PBS
      treated mice and were more resistant to eccentric contraction-induced force drop
      after eccentric lengthening contractions. In summary, sActRIIB pretreatment
      attenuated hypoxia-induced muscle dysfunction. These data suggest that targeting
      the ActRIIB is an effective strategy to counter hypoxia-induced muscle
      dysfunction and to preacclimatize to hypoxia in clinical or high-altitude
      settings.

PMID- 19864339
TI  - Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic
      preconditioning.
AB  - We have previously demonstrated placentas from laboring deliveries at high
      altitude have lower binding of hypoxia-inducible transcription factor (HIF) to
      DNA than those from low altitude. It has recently been reported that labor causes
      oxidative stress in placentas, likely due to ischemic hypoxic insult. We
      hypothesized that placentas of high-altitude residents acquired resistance, in
      the course of their development, to oxidative stress during labor. Full-thickness
      placental tissue biopsies were collected from laboring vaginal and nonlaboring
      cesarean-section term (37-41 wk) deliveries from healthy pregnancies at sea level
      and at 3,100 m. After freezing in liquid nitrogen within 5 min of delivery, we
      quantified hydrophilic and lipid metabolites using (31)P and (1)H NMR
      metabolomics. Metabolic markers of oxidative stress, increased glycolysis, and
      free amino acids were present in placentas following labor at sea level, but not
      at 3,100 m. In contrast, at 3,100 m, the placentas were characterized by the
      presence of concentrations of stored energy potential (phosphocreatine),
      antioxidants, and low free amino acid concentrations. Placentas from pregnancies
      at sea level subjected to labor display evidence of oxidative stress. However,
      laboring placentas at 3,100 m have little or no oxidative stress at the time of
      delivery, suggesting greater resistance to ischemia-reperfusion. We postulate
      that hypoxic preconditioning might occur in placentas that develop at high
      altitude.

PMID- 19864342
TI  - The utility of comparative genetics to inform breast cancer prevention
      strategies.
AB  - My research seeks to aid in developing approaches to prevent breast cancer. This
      research evolved from our early empirical studies for discovering natural
      compounds with anticancer activities, coupled with clinical evaluation to a
      genetics-driven approach to prevention. This centers on the use of comparative
      genomics to discover risk-modifying alleles that could help define population and
      individual risk and also serve as potential prevention drugable targets to
      mitigate risk. Here, we initially fine map mammary cancer loci in a rat
      carcinogenesis model and then evaluate their human homologs in breast cancer case
      control association studies. This approach has yielded promising results,
      including the finding that the compound rat QTL Mcs5a's human homologous region
      was associated with breast cancer risk. These and related findings have the
      potential to yield advancements both in translation-prevention research and in
      basic molecular genetics.

PMID- 19864343
TI  - Is there a declining trend in ovarian function among infertility clinic patients?
AB  - BACKGROUND: There is a growing body of evidence that testicular function has
      decreased rapidly over the last 50 years. However, much less is known about
      corresponding trends in ovarian function. Herein, we examine the temporal changes
      in ovarian function in a large sample of infertile patients from the Czech
      Republic over a period of 14 years. METHODS: In a retrospective study, we
      analysed a large body of data from women, 20-40 years of age, undergoing IVF/ICSI
      treatment between 1995 and 2008. We defined ovarian function using five
      variables: basal FSH level, estradiol (E2) level on the day of HCG
      administration, dose of gonadotrophins used for ovarian stimulation, number of
      retrieved oocytes and dose of gonadotrophins per oocyte. Controlling
      simultaneously for temporal changes in patient age and stimulation protocol, we
      applied generalized additive models to describe the temporal trends. RESULTS:
      During the study period the mean age of the study population increased by 2.7
      years. Whereas the basal FSH and gonadotrophin dose did not change over time, the
      E2 level and oocyte retrieval declined, and the dose of FSH per oocyte increased
      during the study period. CONCLUSIONS: The results are indicative of a small, but
      detectable decrease in ovarian function over a period of 14 years, which is not
      causally related to the ageing population.

PMID- 19864344
TI  - Commentary: Assessing the impact of breastfeeding on child health: where
      conventional methods alone fall short for reliably establishing causal inference.

PMID- 19864345
TI  - Commentary: Heart rate and blood pressure: risk factors or risk markers?

PMID- 19864346
TI  - Commentary: Early stimulation and child development.

PMID- 19864347
TI  - One confused patient, many confused physicians: a case of delayed post-hypoxic
      leucoencephalopathy.

PMID- 19864348
TI  - Low rates of treatment in postmenopausal women with a history of low trauma
      fractures: results of audit in a Fracture Liaison Service.
AB  - BACKGROUND: A past history of low trauma fracture is a strong risk factor for
      future fractures in postmenopausal women and national guidance recommends
      treatment in the majority of such women AIM: To establish the prevalence of bone
      protective therapy use in postmenopausal women with a history of low trauma
      fracture Design and METHODS: Clinical audit of 1641 postmenopausal women
      presenting with a low trauma fracture to the Fracture Liaison Service at
      Addenbrooke's Hospital, Cambridge between January 2006 and December 2007.
      RESULTS: A total of 526 (31%) women presenting with a fracture had a past history
      of fracture, defined as a low trauma fracture after the age of 45 years. The
      wrist was the most common site of previous fracture, followed by hip, hand or
      foot, lower leg and humerus. Of these women, only 27.6% were receiving bone
      protective therapy with a bisphosphonate (89%) or other medication. Calcium and
      vitamin D supplements were received by 35.6%. The highest rates of treatment were
      seen for spine and hip fracture (61.9 and 49.3%, respectively). Only 45.1% of
      women aged 75 years and over with a previous history of fracture were receiving
      bone protective therapy. CONCLUSION: The results of our audit demonstrate low
      rates of treatment in postmenopausal women with a history of low trauma fracture.
      Better education of healthcare professionals, more consistent recording of
      fractures in primary care and the use of clearly defined care pathways that
      involve patients and their carers provide rational approaches to reducing this
      care gap.

PMID- 19864349
TI  - The swinging thyroid in hepatitis C infection and interferon therapy.

PMID- 19864350
TI  - A composite approach to thoracic aortic stent grafting.
AB  - Thoracic endovascular aortic repair has become the preferred modality for the
      treatment of diverse aortic pathologies of the thoracic aorta. This report is the
      first to describe the use of 2 different devices for successful exclusion of a
      dissecting thoracic aneurysm.

PMID- 19864351
TI  - Economic crisis, unemployment and public health.

PMID- 19864354
TI  - Integration of herbal medicine in primary care in Israel: a jewish-arab cross
      cultural perspective.
AB  - Herbal medicine is a prominent complementary and alternative medicine (CAM)
      modality in Israel based on the country's natural diversity and impressive
      cultural mosaic. In this study, we compared cross-cultural perspectives of
      patients attending primary care clinics in northern Israel on herbal medicine
      specifically and CAM generally, and the possibility of integrating them within
      primary care. Research assistants administered a questionnaire to consecutive
      patients attending seven primary care clinics. About 2184 of 3713 respondents
      (59%) defined themselves as Muslims, Christians or Druze (henceforth Arabs) and
      1529 (41%) as Jews. Arab respondents reported more use of herbs during the
      previous year (35 versus 27.8% P = .004) and of more consultations with herbal
      practitioners (P < .0001). Druze reported the highest rate of herbal
      consultations (67.9%) and Ashkenazi Jews the lowest rate (45.2%). About 27.5% of
      respondents supported adding a herbal practitioner to their clinic's medical team
      if CAM were to be integrated within primary care. Both Arabs and Jews report
      considerable usage of herbal medicine, with Arabs using it significantly more.
      Cross-cultural perspectives are warranted in the study of herbal medicine use in
      the Arab and Jewish societies.

PMID- 19864355
TI  - Diagnosis of diabetes using the oral glucose tolerance test.

PMID- 19864356
TI  - Vitamin D and falls. Time for a moratorium on vitamin D meta-analyses?

PMID- 19864357
TI  - Vitamin D and falls. Information on harm is missing.

PMID- 19864358
TI  - Mental capacity. Autonomy or life saving treatment for the mentally vulnerable?

PMID- 19864360
TI  - Lack of palliative care causes unnecessary suffering for India's terminally ill
      people.

PMID- 19864363
TI  - Control of hepatitis B and C worldwide.

PMID- 19864365
TI  - Occupational blood exposure accidents in the Netherlands.
AB  - BACKGROUND: To make proper evaluation of prevention policies possible, data on
      the incidence and associated medical costs of occupational blood exposure
      accidents in the Netherlands are needed. METHODS: Descriptive analysis of blood
      exposure accidents and risk estimates for occupational groups. Costs of handling
      accidents were calculated. RESULTS: Each year, an estimated 13,000-15,000 blood
      exposure accidents are reported in the Netherlands, 95% in occupational settings.
      Hepatitis B (HBV) vaccination is offered free of charge only to people in risk
      groups, the seroprevalence of HBV, hepatitis C (HCV) and human immunodeficiency
      virus (HIV) is low and few infections are related to blood exposure accidents.
      High-risk accidents occur mainly in hospitals. In nursing homes and home care
      settings, the majority of the accidents are low-risk. Limited data are available
      about occurrence of accidents in other occupational groups. Associated medical
      costs from occupational blood exposure accidents are mainly determined by the
      initial risk management. CONCLUSIONS: Accidents must be managed effectively to
      prevent infection and reduce anxiety in injured employees. While strategies to
      reduce HCV and HIV infection should be primarily aimed at reducing the occurrence
      of high-risk accidents, vaccination can prevent HBV infection and cut the costs
      of handling low-risk accidents. The implementation of vaccination strategies,
      safe working policies and the proper use of safe equipment should be monitored
      better.

PMID- 19864366
TI  - A cost-utility analysis of adding a bivalent or quadrivalent HPV vaccine to the
      Irish cervical screening programme.
AB  - BACKGROUND: Cervical cancer is a leading cause of death worldwide, and in Ireland
      it is the ninth most commonly diagnosed cancer in women. Almost 100% of these
      cancers are caused by human papillomavirus (HPV) infection. Two newly developed
      vaccines against HPV infection have become available. This study is a cost
      utility analysis of the HPV vaccine in Ireland, and it compares the cost
      effectiveness profiles of the two vaccines. METHODS: A cost-utility analysis of
      the HPV vaccine in Ireland was performed using a Markov model. A cohort of
      screened and vaccinated women was compared with an unvaccinated screened cohort,
      and both cohorts were followed over their lifetimes. The model looked at uptake
      of services related to HPV disease in both cohorts. Outcomes were measured in
      quality adjusted life years (QALYs). Extensive sensitivity analysis was done.
      RESULTS: For the base case analysis, the model showed that the incremental cost
      effectiveness ratio (ICER) for quadrivalent HPV vaccination would be 25,349
      euros/QALY and 30,460 euros/QALY for the bivalent vaccine. The ICER for the
      quadrivalent vaccine ranged from 2877 euros to 36,548 euros, and for the bivalent
      from 3399 euros to 45,237 euros. At current prices, the bivalent vaccine would
      need to be 22% cheaper than the quadrivalent vaccine in order to have equivalent
      cost effectiveness. CONCLUSION: HPV vaccination has the potential to be very cost
      effective in Ireland. The quadrivalent vaccine is more cost effective than the
      bivalent vaccine.

PMID- 19864371
TI  - Twenty four risk factors responsible for nearly half of annual deaths, says WHO.

PMID- 19864374
TI  - NICE guideline aims to tackle depression in people with chronic physical health.

PMID- 19864375
TI  - Stomatal crypts have small effects on transpiration: a numerical model analysis.
AB  - Stomata arranged in crypts with trichomes are commonly considered to be
      adaptations to aridity due to the additional diffusion resistance associated with
      this arrangement; however, information on the effect of crypts on gas exchange,
      relative to stomata, is sparse. In this study, three-dimensional Finite Element
      models of encrypted stomata were generated using commercial Computational Fluid
      Dynamics software. The models were based on crypt and stomatal architectural
      characteristics of the species Banksia ilicifolia, examined microscopically, and
      variations thereof. In leaves with open or partially closed stomata, crypts
      reduced transpiration by less than 15% compared with nonencrypted, superficially
      positioned stomata. A larger effect of crypts was found only in models with
      unrealistically high stomatal conductances. Trichomes inside the crypt had
      virtually no influence on transpiration. Crypt conductance varied with stomatal
      conductance, boundary layer conductance, and ambient relative humidity, as these
      factors modified the three-dimensional diffusion patterns inside crypts. It was
      concluded that it is unlikely that the primary function of crypts and crypt
      trichomes is to reduce transpiration.

PMID- 19864376
TI  - A UL47 gene deletion mutant of bovine herpesvirus type 1 exhibits impaired growth
      in cell culture and lack of virulence in cattle.
AB  - Tegument protein VP8 encoded by the U(L)47 gene of bovine herpesvirus type 1 (BHV
      1) is the most abundant constituent of mature virions. In the present report, we
      describe the characterization of U(L)47 gene-deleted BHV-1 in cultured cells and
      its natural host. The U(L)47 deletion mutant exhibited reduced plaque size and
      more than 100-fold decrease in intracellular and extracellular viral titers in
      cultured cells. Ultrastructural observations of infected cells showed normal
      maturation of BHV-1 virions in the absence of VP8. There was no evidence for a
      change in immediate-early gene activator function of VP16 in the U(L)47 deletion
      mutant virus-infected cells, since bovine ICP4 mRNA and protein levels were
      similar to those in the wild-type and revertant virus-infected cells throughout
      the course of infection. Whereas VP16, glycoprotein C (gC), gB, and VP5 were
      expressed to wild-type levels in the U(L)47 deletion mutant-infected cells, the
      gD and VP22 protein levels were significantly reduced. The reduction in gD
      protein was associated with increased turnover of the protein. Furthermore, some
      of the analyzed early and late proteins were expressed with earlier kinetics in
      the absence of VP8. Extracellular virions of the U(L)47 deletion mutant contained
      reduced amounts of gD, gB, gC, and VP22 but similar amounts of VP16 compared to
      those of wild-type or revertant virus particles. In addition, the U(L)47 gene
      product was indispensable for BHV-1 replication in vivo, since no clinical
      manifestations or viral shedding were detected in the U(L)47 deletion mutant
      infected calves, and the virus failed to induce significant levels of humoral and
      cellular immunity.

PMID- 19864377
TI  - Late domain-independent rescue of a release-deficient Moloney murine leukemia
      virus by the ubiquitin ligase itch.
AB  - Moloney murine leukemia virus (MoMLV) Gag utilizes its late (L) domain motif PPPY
      to bind members of the Nedd4-like ubiquitin ligase family. These interactions
      recruit components of the cell's budding machinery that are critical for virus
      release. MoMLV Gag contains two additional L domains, PSAP and LYPAL, that are
      believed to drive residual MoMLV release via interactions with cellular proteins
      Tsg101 and Alix, respectively. We found that overexpression of Tsg101 or Alix
      failed to rescue the release of PPPY-deficient MoMLV via these other L domains.
      However, low-level expression of the ubiquitin ligase Itch potently rescued the
      release and infectivity of MoMLV lacking PPPY function. In contrast, other
      ubiquitin ligases such as WWP1, Nedd4.1, Nedd4.2, and Nedd4.2s did not rescue
      this release-deficient virus. Efficient rescue required the ubiquitin ligase
      activity of Itch and an intact C2 domain but not presence of the endophilin
      binding site. Additionally, we found Itch to immunoprecipitate with MoMLV Gag
      lacking the PPPY motif and to be incorporated into rescued MoMLV particles. The
      PSAP and LYPAL motifs were dispensable for Itch-mediated virus rescue, and their
      absence did not affect the incorporation of Itch into the rescued particles. Itch
      mediated rescue of release-defective MoMLV was sensitive to inhibition by
      dominant-negative versions of ESCRT-III components and the VPS4 AAA ATPase,
      indicating that Itch-mediated correction of MoMLV release defects requires the
      integrity of the host vacuolar sorting protein pathway. RNA interference
      knockdown of Itch suppressed the residual release of the MoMLV lacking the PPPY
      motif. Interestingly, Itch stimulation of the PPPY-deficient MoMLV release was
      accompanied by the enhancement of Gag ubiquitination and the appearance of new
      ubiquitinated Gag proteins in virions. Together, these results suggest that Itch
      can facilitate MoMLV release in an L domain-independent manner via a mechanism
      that requires the host budding machinery and involves Gag ubiquitination.

PMID- 19864378
TI  - Formaldehyde-inactivated whole-virus vaccine protects a murine model of
      enterovirus 71 encephalomyelitis against disease.
AB  - Enterovirus 71 (EV71) causes childhood hand, foot, and mouth disease and
      neurological complications, and no vaccines or therapeutic drugs are currently
      available. Formaldehyde-inactivated whole-virus vaccines derived from EV71
      clinical isolates and a mouse-adapted virus (MAV) were tested in a mouse model of
      EV71 encephalomyelitis. After only two immunizations, given to mice at 1 and 7
      days of age, the MAV vaccine protected mice at 14 days of age from disease.
      Tissues from immunized mice were negative for virus by viral culture, reverse
      transcriptase PCR, immunohistochemistry analysis, and in situ hybridization.
      Cross-neutralizing EV71 antibodies to strains with genotypes B3, B4, and C1 to C5
      generated in immunized adult mice were able to passively protect 14-day-old mice
      from disease.

PMID- 19864379
TI  - Differential downregulation of ACE2 by the spike proteins of severe acute
      respiratory syndrome coronavirus and human coronavirus NL63.
AB  - The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and
      NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown
      that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression
      and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet
      unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding
      with higher efficiency than NL63-S. Shedding most likely accounted for the
      previously observed ACE2 downregulation but was dispensable for viral
      replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2
      positive Vero cells and reduced ACE2 expression, indicating robust receptor
      interference in the context of SARS-CoV but not NL63 infection.

PMID- 19864380
TI  - The single-stranded DNA genome of novel archaeal virus halorubrum pleomorphic
      virus 1 is enclosed in the envelope decorated with glycoprotein spikes.
AB  - Only a few archaeal viruses have been subjected to detailed structural analyses.
      Major obstacles have been the extreme conditions such as high salinity or
      temperature needed for the propagation of these viruses. In addition, unusual
      morphotypes of many archaeal viruses have made it difficult to obtain further
      information on virion architectures. We used controlled virion dissociation to
      reveal the structural organization of Halorubrum pleomorphic virus 1 (HRPV-1)
      infecting an extremely halophilic archaeal host. The single-stranded DNA genome
      is enclosed in a pleomorphic membrane vesicle without detected nucleoproteins.
      VP4, the larger major structural protein of HRPV-1, forms glycosylated spikes on
      the virion surface and VP3, the smaller major structural protein, resides on the
      inner surface of the membrane vesicle. Together, these proteins organize the
      structure of the membrane vesicle. Quantitative lipid comparison of HRPV-1 and
      its host Halorubrum sp. revealed that HRPV-1 acquires lipids nonselectively from
      the host cell membrane, which is typical of pleomorphic enveloped viruses.

PMID- 19864381
TI  - A trans-complementing recombination trap demonstrates a low propensity of
      flaviviruses for intermolecular recombination.
AB  - Intermolecular recombination between the genomes of closely related RNA viruses
      can result in the emergence of novel strains with altered pathogenic potential
      and antigenicity. Although recombination between flavivirus genomes has never
      been demonstrated experimentally, the potential risk of generating undesirable
      recombinants has nevertheless been a matter of concern and controversy with
      respect to the development of live flavivirus vaccines. As an experimental system
      for investigating the ability of flavivirus genomes to recombine, we developed a
      "recombination trap," which was designed to allow the products of rare
      recombination events to be selected and amplified. To do this, we established
      reciprocal packaging systems consisting of pairs of self-replicating subgenomic
      RNAs (replicons) derived from tick-borne encephalitis virus (TBEV), West Nile
      virus (WNV), and Japanese encephalitis virus (JEV) that could complement each
      other in trans and thus be propagated together in cell culture over multiple
      passages. Any infectious viruses with intact, full-length genomes that were
      generated by recombination of the two replicons would be selected and enriched by
      end point dilution passage, as was demonstrated in a spiking experiment in which
      a small amount of wild-type virus was mixed with the packaged replicons. Using
      the recombination trap and the JEV system, we detected two aberrant recombination
      events, both of which yielded unnatural genomes containing duplications.
      Infectious clones of both of these genomes yielded viruses with impaired growth
      properties. Despite the fact that the replicon pairs shared approximately 600
      nucleotides of identical sequence where a precise homologous crossover event
      would have yielded a wild-type genome, this was not observed in any of these
      systems, and the TBEV and WNV systems did not yield any viable recombinant
      genomes at all. Our results show that intergenomic recombination can occur in the
      structural region of flaviviruses but that its frequency appears to be very low
      and that therefore it probably does not represent a major risk in the use of
      live, attenuated flavivirus vaccines.

PMID- 19864383
TI  - Hepatitis B and hepatitis C virus replication upregulates serine protease
      inhibitor Kazal, resulting in cellular resistance to serine protease-dependent
      apoptosis.
AB  - Hepatitis B and C viruses (HBV and HCV, respectively) are different and distinct
      viruses, but there are striking similarities in their disease potential.
      Infection by either virus can cause chronic hepatitis, liver cirrhosis, and
      ultimately, liver cancer, despite the fact that no pathogenetic mechanisms are
      known which are shared by the two viruses. Our recent studies have suggested that
      replication of either of these viruses upregulates a cellular protein called
      serine protease inhibitor Kazal (SPIK). Furthermore, the data have shown that
      cells containing HBV and HCV are more resistant to serine protease-dependent
      apoptotic death. Since our previous studies have shown that SPIK is an inhibitor
      of serine protease-dependent apoptosis, it is hypothesized that the upregulation
      of SPIK caused by HBV and HCV replication leads to cell resistance to apoptosis.
      The evasion of apoptotic death by infected cells results in persistent viral
      replication and constant liver inflammation, which leads to gradual accumulation
      of genetic changes and eventual development of cancer. These findings suggest a
      possibility by which HBV and HCV, two very different viruses, can share a common
      mechanism in provoking liver disease and cancer.

PMID- 19864382
TI  - Dual mechanism of impairment of interleukin-7 (IL-7) responses in human
      immunodeficiency virus infection: decreased IL-7 binding and abnormal activation
      of the JAK/STAT5 pathway.
AB  - Interleukin-7 (IL-7) plays a central role in controlling the homeostasis of both
      naive and long-term-memory CD4(+) T cells. To better understand how human
      immunodeficiency virus (HIV) perturbs CD4(+) T-cell homeostasis, we performed a
      detailed analysis of IL-7R expression, IL-7 binding, and IL-7-dependent early and
      late signaling events in CD4(+) T-cell subsets from viremic and efficiently
      treated patients. HIV infection differentially affected the expression of IL-7
      receptor (IL-7R) chains, with decreases in IL-7Ralpha/CD127 expression in the
      memory subset and increases in gammac/CD132 expression in all CD4(+) T cells.
      This resulted in preserved IL-7 binding in the naive compartment and decreased IL
      7 binding in the memory compartment of viremic patients. Accordingly, the
      percentages of cells signaling in response to IL-7, as measured by pSTAT5
      induction, were decreased in memory subsets, including conventional CD4(+) T
      cells and regulatory T cells. However, the levels of pSTAT5 induction per
      responding cell, as measured by pSTAT5 fluorescence intensity, were increased
      within all naive and memory CD4(+) T-cell subsets of viremic patients. The basal
      level of pSTAT5 was also increased, indicating a constitutive activation of the
      JAK/STAT5 pathway. IL-7 functional responses, as measured by Bcl-2, CD25, and
      Foxp3 induction, were impaired in viremic patient CD4(+) T cells, suggesting that
      chronic activation led to downstream defects in the STAT5 signaling pathway.
      Thus, HIV infection perturbs IL-7 responses at both receptor binding and
      signaling steps, which likely compromises the regenerative capacity of the CD4(+)
      T-cell pool and may contribute to CD4(+) T-cell depletion.

PMID- 19864384
TI  - Analysis of herpes simplex virus type 1 DNA packaging signal mutations in the
      context of the viral genome.
AB  - The minimal signal required for the cleavage and packaging of replicated
      concatemeric herpes simplex virus type 1 (HSV-1) DNA corresponds to an
      approximately 200-bp fragment, Uc-DR1-Ub, spanning the junction of the genomic L
      and S segments. Uc and Ub occupy positions adjacent to the L and S termini and
      contain motifs (pac2 and pac1, respectively) that are conserved near the ends of
      other herpesvirus genomes. We have used homologous Red/ET recombination in
      Escherichia coli to introduce wild-type and specifically mutated Uc-DR1-Ub
      fragments into an ectopic site of a cloned HSV-1 genome from which the resident
      packaging signals had been previously deleted. The resulting constructs were
      transfected into mammalian cells, and their abilities to replicate and become
      encapsidated, generate Uc- and Ub-containing terminal fragments, and give rise to
      progeny virus were assessed. In general, the results obtained agree well with
      previous observations made using amplicons and confirm roles for the pac2 T
      element in the initiation of DNA packaging and for the GC-rich motifs flanking
      the pac1 T element in termination. In contrast to a previous report, the sequence
      of the DR1 element was also crucial for DNA packaging. Following repair of the
      resident packaging signals in mammalian cells, recombination occurred at high
      frequency in progeny virus between the repaired sequences and mutated Uc-DR1-Ub
      inserts. This restored the ability of mutated Uc-DR1-Ub inserts to generate
      terminal fragments, although these were frequently larger than expected from
      simple repair of the original lesion.

PMID- 19864385
TI  - Conserved residues in the UL24 protein of herpes simplex virus 1 are important
      for dispersal of the nucleolar protein nucleolin.
AB  - The UL24 family of proteins is widely conserved among herpesviruses. We
      demonstrated previously that UL24 of herpes simplex virus 1 (HSV-1) is important
      for the dispersal of nucleolin from nucleolar foci throughout the nuclei of
      infected cells. Furthermore, the N-terminal portion of UL24 localizes to nuclei
      and can disperse nucleolin in the absence of any other viral proteins. In this
      study, we tested the hypothesis that highly conserved residues in UL24 are
      important for the ability of the protein to modify the nuclear distribution of
      nucleolin. We constructed a panel of substitution mutations in UL24 and tested
      their effects on nucleolin staining patterns. We found that modified UL24
      proteins exhibited a range of subcellular distributions. Mutations associated
      with a wild-type localization pattern for UL24 correlated with high levels of
      nucleolin dispersal. Interestingly, mutations targeting two regions, namely,
      within the first homology domain and overlapping or near the previously
      identified PD-(D/E)XK endonuclease motif, caused the most altered UL24
      localization pattern and the most drastic reduction in its ability to disperse
      nucleolin. Viral mutants corresponding to the substitutions G121A and E99A/K101A
      both exhibited a syncytial plaque phenotype at 39 degrees C. vUL24-E99A/K101A
      replicated to lower titers than did vUL24-G121A or KOS. Furthermore, the
      E99A/K101A mutation caused the greatest impairment of HSV-1-induced dispersal of
      nucleolin. Our results identified residues in UL24 that are critical for the
      ability of UL24 to alter nucleoli and further support the notion that the
      endonuclease motif is important for the function of UL24 during infection.

PMID- 19864386
TI  - Herpes simplex virus proteins ICP27 and UL47 associate with polyadenylate-binding
      protein and control its subcellular distribution.
AB  - Human pathogenic viruses manipulate host cell translation machinery to ensure
      efficient expression of viral genes and to thwart host cell protein synthesis.
      Viral strategies include cleaving translation factors, manipulating translation
      factor abundance and recruitment into translation initiation complexes, or
      expressing viral translation factor analogs. Analyzing translation factors in
      herpes simplex virus type 1 (HSV-1)-infected HeLa cells, we found diminished
      association of the polyadenylate-binding protein (PABP) with the cap-binding
      complex. Although total PABP levels were unchanged, HSV-1 infection prompted
      accumulation of cytoplasmic PABPC1, but not its physiologic binding partner PABP
      interacting protein 2 (Paip2), in the nucleus. Using glutathione S-transferase
      PABP pull-down and proteomic analyses, we identified several viral proteins
      interacting with PABPC1 including tegument protein UL47 and infected-cell protein
      ICP27. Transient expression of ICP27 and UL47 in HeLa cells suggested that ICP27
      and UL47 jointly displace Paip2 from PABP. ICP27 expression alone was sufficient
      to cause PABPC1 redistribution to the nucleus. ICP27 and UL47 did not alter
      translation efficiency of transfected reporter RNAs but modulated transcript
      abundance and expression of reporter cDNAs in transfected cells. This indicates
      that redistribution of PABPC1 may be involved in co- and posttranscriptional
      regulation of mRNA processing and/or nuclear export by HSV-1 gene regulatory
      proteins.

PMID- 19864387
TI  - Production and function of the cytoplasmic deproteinized relaxed circular DNA of
      hepadnaviruses.
AB  - Removal of genome-bound viral DNA polymerase ought to be an essential step in the
      formation of hepadnavirus covalently closed circular DNA (cccDNA). We previously
      demonstrated that deproteinized (DP) relaxed circular DNA (rcDNA) of hepatitis B
      virus (HBV) existed in both the cytoplasm and nuclei of infected cells and the
      vast majority of cytoplasmic DP rcDNA was associated with DNase I-permeable
      nucleocapsids. In our efforts to investigate the role of the cytoplasmic DP rcDNA
      in cccDNA formation, we demonstrated that rcDNA deproteinization could occur in
      an endogenous DNA polymerase reaction with either virion-derived or intracellular
      nucleocapsids. As observed in the cytoplasm of virally infected cells, in vitro
      deproteinization requires the maturation of plus-strand DNA and results in
      changes in nucleocapsid structure that render the DP rcDNA susceptible to DNase I
      digestion. Remarkably, we found that the cytoplasmic DP rcDNA-containing
      nucleocapsids could be selectively immunoprecipitated with an antibody against
      the carboxyl-terminal peptide of HBV core protein and are associated with
      cellular nuclear transport receptors karyopherin-alpha and -beta. Moreover,
      transfection of small interfering RNA targeting karyopherin-beta1 mRNA or
      expression of a dominant-negative karyopherin-beta1 in a stable cell line
      supporting HBV replication resulted in the accumulation of DP rcDNA in cytoplasm
      and reduction of nuclear DP rcDNA and cccDNA. Our results thus favor a hypothesis
      that completion of plus-strand DNA synthesis triggers the genomic DNA
      deproteinization and structural changes of nucleocapsids, which leads to the
      exposure of nuclear localization signals in the C terminus of core protein and
      mediates the nuclear transportation of DP rcDNA via interaction with karyopherin
      alpha and -beta.

PMID- 19864388
TI  - Activation of an antiviral response in normal but not transformed mouse cells: a
      new determinant of minute virus of mice oncotropism.
AB  - Parvovirus minute virus of mice (MVMp) is endowed with oncotropic properties so
      far ascribed only to the dependency of the virus life cycle on cellular factors
      expressed during S phase and/or modulated by malignant transformation. For other
      viruses oncotropism relies on their inability to circumvent type I interferon
      (IFN)-induced innate antiviral mechanisms, the first line of defense triggered by
      normal cells against viral infections. These agents propagate, therefore,
      preferentially in transformed/tumor cells, which often lack functional antiviral
      mechanisms. The present study aimed at investigating whether antiviral processes
      also contribute to MVMp oncotropism. Our results demonstrate that in contrast to
      MVMp-permissive transformed mouse A9 fibroblasts, freshly isolated normal
      counterparts (mouse embryonic fibroblasts [MEFs]) mount, through production and
      release of type I IFNs upon their infection, an antiviral response against MVMp
      lytic multiplication. Pretreatment of MEFs with a type I IFN-beta-neutralizing
      antibody, prior to MVMp infection, inhibits the virus-triggered antiviral
      response and improves the fulfillment of the MVMp life cycle. Our results also
      show that part of the A9 permissiveness to MVMp relies on the inability to
      produce type I IFNs upon parvovirus infection, a feature related either to an A9
      intrinsic deficiency of this process or to an MVMp-triggered inhibitory
      mechanism, since stimulation of these cells by exogenous IFN-beta strongly
      inhibits the parvovirus life cycle. Taken together, our results demonstrate for
      the first time that parvovirus infection triggers an innate antiviral response in
      normal cells and suggest that the MVMp oncotropism depends at least in part on
      the failure of infected transformed cells to mount such a response.

PMID- 19864389
TI  - Generation of live attenuated novel influenza virus A/California/7/09 (H1N1)
      vaccines with high yield in embryonated chicken eggs.
AB  - Several live attenuated influenza virus A/California/7/09 (H1N1) (CA09) candidate
      vaccine variants that possess the hemagglutinin (HA) and neuraminidase (NA) gene
      segments from the CA09 virus and six internal protein gene segments from the cold
      adapted influenza virus A/Ann Arbor/6/60 (H2N2) virus were generated by reverse
      genetics. The reassortant viruses replicated relatively poorly in embryonated
      chicken eggs. To improve virus growth in eggs, reassortants expressing the HA and
      NA of CA09 were passaged in MDCK cells and variants exhibiting large-plaque
      morphology were isolated. These variants replicated at levels approximately 10
      fold higher than the rate of replication of the parental strains in embryonated
      chicken eggs. Sequence analysis indicated that single amino acid changes at
      positions 119, 153, 154, and 186 were responsible for the improved growth
      properties in MDCK cells and eggs. In addition, the introduction of a mutation at
      residue 155 that was previously shown to enhance the replication of a 1976 swine
      influenza virus also significantly improved the replication of the CA09 virus in
      eggs. Each variant was further evaluated for receptor binding preference,
      antigenicity, attenuation phenotype, and immunogenicity. Mutations at residues
      153, 154, and 155 drastically reduced viral antigenicity, which made these
      mutants unsuitable as vaccine candidates. However, changes at residues 119 and
      186 did not affect virus antigenicity or immunogenicity, justifying their
      inclusion in live attenuated vaccine candidates to protect against the currently
      circulating 2009 swine origin H1N1 viruses.

PMID- 19864390
TI  - Vaccination to induce antibodies blocking the CX3C-CX3CR1 interaction of
      respiratory syncytial virus G protein reduces pulmonary inflammation and virus
      replication in mice.
AB  - Respiratory syncytial virus (RSV) infection causes substantial morbidity and some
      deaths in the young and elderly worldwide. There is no safe and effective vaccine
      available, although it is possible to reduce the hospitalization rate for high
      risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the
      immune response to infection, a feature linked in part to RSV G protein CX3C
      chemokine mimicry. This study determined if vaccination with G protein
      polypeptides or peptides spanning the central conserved region of the G protein
      could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and
      disease pathogenesis mediated by RSV infection. The results show that mice
      vaccinated with G protein peptides or polypeptides containing the CX3C motif
      generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis,
      reduce lung virus titers, and prevent body weight loss and pulmonary
      inflammation. The results suggest that RSV vaccines that induce antibodies that
      block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious
      RSV vaccine strategy.

PMID- 19864391
TI  - Insulin-degrading enzyme binds to the nonglycosylated precursor of varicella
      zoster virus gE protein found in the endoplasmic reticulum.
AB  - Insulin degradation enzyme (IDE) is a 110-kDa zinc metalloprotease found in the
      cytosol of all cells. IDE degrades insulin and a variety of small proteins
      including amyloid-beta. Recently, IDE has been proposed as the receptor for
      varicella-zoster virus (VZV) attachment. During our reassessment, some of the
      original studies were repeated and expanded in scope. We first confirmed that IDE
      antibody reduced VZV spread. For additional controls, we repeated the same
      experiments with herpes simplex virus (HSV)-infected cells as well as uninfected
      cells. There was a visible reduction in HSV spread but less than seen in the VZV
      system. Of greater importance, IDE antibody also inhibited the growth of
      uninfected cells. Second, we repeated the coprecipitation assays. We confirmed
      that antibodies to VZV gE (open reading frame 68) coprecipitated IDE and that
      anti-IDE antibody coprecipitated gE. However, the detected gE protein was not the
      mature 98-kDa form; rather, it was a precursor 73-kDa gE form found in the
      endoplasmic reticulum. Additional control experiments included VZV-infected cell
      cultures treated with tunicamycin to block gE glycosylation in the endoplasmic
      reticulum; again, the anti-IDE antibody coprecipitated a 73-kDa gE product.
      Finally, Orbitrap mass spectrometry analysis of a chromatographically purified gE
      sample revealed four cellular proteins associated with the unfolded protein
      response: BiP (HSPA5), HSPA8, HSPD1, and PPIA (peptidyl-propyl cis-trans
      isomerase). We conclude that IDE protease binds to the 73-kDa gE precursor and
      that this event occurs in the cytosol but not as a receptor/ligand interaction.

PMID- 19864392
TI  - Evaluation of CD4-CD4i antibody architectures yields potent, broadly cross
      reactive anti-human immunodeficiency virus reagents.
AB  - The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) has
      several adaptations that allow the virus to evade antibody neutralization.
      Nevertheless, a few broadly cross-reactive neutralizing antibodies as well as
      reagents containing portions of CD4, the HIV receptor, have demonstrated partial
      efficacy in suppressing viral replication. One type of reagent designed for
      improved HIV neutralization fuses the CD4 D1-D2 domains to the variable regions
      of an antibody recognizing the CD4-induced (CD4i) coreceptor binding site on the
      gp120 portion of the HIV envelope spike. We designed, expressed, purified, and
      tested the neutralization potencies of CD4-CD4i antibody reagents with different
      architectures, antibody combining sites, and linkers. We found that fusing CD4 to
      the heavy chain of the CD4i antibody E51 yields a bivalent reagent including an
      antibody Fc region that expresses well, is expected to have a long serum half
      life, and has comparable or greater neutralization activity than well-known
      broadly neutralizing anti-HIV antibodies. A CD4 fusion with the anti-HIV
      carbohydrate antibody 2G12 also results in a potent neutralizing reagent with
      more broadly neutralizing activity than 2G12 alone.

PMID- 19864393
TI  - Crimean-Congo hemorrhagic fever virus-encoded ovarian tumor protease activity is
      dispensable for virus RNA polymerase function.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus (genus
      Nairovirus, family Bunyaviridae) associated with high case fatality disease
      outbreaks in regions of Africa, Europe, and Asia. The CCHFV genome consists of
      three negative-strand RNA segments, S, M, and L. The unusually large virus L
      polymerase protein and the need for biosafety level 4 (BSL-4) containment
      conditions for work with infectious virus have hampered the study of CCHFV
      replication. The L protein has an ovarian tumor (OTU) protease domain located in
      the N terminus, which has led to speculation that the protein may be
      autoproteolytically cleaved to generate the active virus L polymerase and
      additional functions. We report the successful development of efficient CCHFV
      helper virus-independent S, M, and L segment minigenome systems for analysis of
      virus RNA and protein features involved in replication. The virus RNA segment S,
      M, and L untranslated regions were found to be similar in support of replication
      of the respective minigenomes. In addition, the OTU domain located in the N
      terminus of the expressed virus L protein was shown to be a functional protease.
      However, no evidence of L protein autoproteolytic processing was found, and the
      OTU protease activity was dispensable for virus RNA replication. Finally,
      physiologically relevant doses of ribavirin inhibited CCHFV minigenome
      replication. These results demonstrated the utility of the minigenome system for
      use in BSL-2 laboratory settings to analyze CCHFV biology and in antiviral drug
      discovery programs for this important public health and bioterrorism threat.

PMID- 19864394
TI  - The oncolytic activity of Newcastle disease virus NDV-HUJ on chemoresistant
      primary melanoma cells is dependent on the proapoptotic activity of the inhibitor
      of apoptosis protein Livin.
AB  - Patients with advanced melanoma usually do not benefit from conventional
      chemotherapy treatment. There is therefore a true need for a new kind of therapy
      for melanoma. One factor responsible for the poor prognosis of melanoma is the
      inhibitor of apoptosis protein (IAP) family member Livin. In this study, we
      applied a novel approach for the treatment of melanoma, using a unique strain of
      the oncolytic Newcastle disease virus (NDV-HUJ). We found that, unlike
      chemotherapeutic drugs, NDV-HUJ, a one-cycle replicating virus, overcomes the
      resistance to apoptosis of melanoma primary cultures that over express the Livin
      protein. In contrast, melanoma tumor cells that do not express Livin are
      relatively resistant to NDV-HUJ treatment. Furthermore, we show that NDV-HUJ
      induced oncolysis is attributed to the dual function of Livin: although Livin
      inhibits apoptosis through the inhibition of caspases, under the robust apoptotic
      stimulation of NDV-HUJ, caspases can cleave Livin to create a truncated protein
      with a paradoxical proapoptotic activity. Thus, NDV-HUJ is a potent inducer of
      apoptosis that can overcome the antiapoptotic effect of Livin and allow cleavage
      of Livin into the proapoptotic tLivin protein. Moreover, the results indicate
      that the interferon system, which is functional in melanoma, is not involved in
      NDV-induced oncolysis. Taken together, our data offer the possibility of a new
      viral oncolytic treatment for chemoresistant melanoma.

PMID- 19864396
TI  - American Cancer Society perspectives on environmental factors and cancer.
AB  - Cancer prevention is central to the mission of the American Cancer Society (ACS).
      The ACS's prevention activities take many forms, but are primarily focused on
      modifiable risk factors that have been demonstrated to have the largest impact on
      cancer risk in the general population (with particular emphasis on tobacco use
      because of its large impact on cancer), and well-proven policy and program
      interventions. The ACS addresses nutrition, physical inactivity and obesity,
      alcohol consumption, excessive sun exposure, prevention of certain chronic
      infections, and selected other environmental factors through a variety of venues,
      including consensus guidelines (eg, nutrition and physical activity, human
      papillomavirus vaccination) and developing educational materials for health care
      providers and the general public. In contrast to the broad definition of
      environmental factors used by the ACS and most other public health agencies, some
      members of the general public associate the term "environmental" only with toxic
      air and water pollutants and other, predominantly manmade, hazards that people
      encounter, often involuntarily, in their daily life. This article will provide an
      overview of the ACS's approach to the prevention of cancer associated with such
      toxic pollutants in the context of its mission and priorities with respect to
      cancer prevention.

PMID- 19864397
TI  - GAD antibody positivity predicts type 2 diabetes in an adult population.
AB  - OBJECTIVE: To evaluate the significance of GAD antibodies (GADAs) and family
      history for type 1 diabetes (FH(T1)) or type 2 diabetes (FH(T2)) in nondiabetic
      subjects. RESEARCH DESIGN AND METHODS: GADAs were analyzed in 4,976 nondiabetic
      relatives of type 2 diabetic patients or control subjects from Finland.
      Altogether, 289 (5.9%) were GADA(+)-a total of 253 GADA(+) and 2,511 GADA(-)
      subjects participated in repeated oral glucose tolerance tests during a median
      time of 8.1 years. The risk of progression to diabetes was assessed using Cox
      regression analysis. RESULTS: Subjects within the highest quartile of GADA(+)
      (GADA(+)(high)) had more often first-degree FH(T1) (29.2 vs. 7.9%, P < 0.00001)
      and GADA(+) type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs.
      13.3%, P = 0.010) relatives than GADA(-) subjects. During the follow-up, the
      GADA(+) subjects developed diabetes significantly more often than the GADA(-)
      subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA(+)(high)
      conferred a 4.9-fold increased risk of diabetes (95% CI 2.8-8.5) compared with
      GADA(-)-seroconversion to positive during the follow-up was associated with 6.5
      fold (2.8-15.2) and first-degree FH(T1) with 2.2-fold (1.2-4.1) risk of diabetes.
      Only three subjects developed type 1 diabetes, and others had a non-insulin
      dependent phenotype 1 year after diagnosis. GADA(+) and GADA(-) subjects did not
      clinically differ at baseline, but they were leaner and less insulin resistant
      after the diagnosis of diabetes. CONCLUSIONS: GADA positivity clusters in
      families with type 1 diabetes or latent autoimmune diabetes in adults. GADA
      positivity predicts diabetes independently of family history of diabetes, and
      this risk was further increased with high GADA concentrations.

PMID- 19864398
TI  - Cosupplementation of isoflavones, prenylflavonoids, and lignans alters human
      exposure to phytoestrogen-derived 17beta-estradiol equivalents.
AB  - The microbial metabolism of dietary phytoestrogens varies considerably among
      individuals and influences the final exposure to bioactive compounds. In view of
      the increasing number of food supplements combining several classes of
      phytoestrogens, the microbial potential to activate various proestrogens within
      an individual was evaluated in 3 randomized dietary crossovers. Treatment
      allocation was based on participants' eligibility (>45% in vitro bioactivation of
      >or=2 separate proestrogens by fecal cultures; n = 40/100). After a run-in of
      >or=4 d, participants were given soy-, hop-, and/or flax-based food supplements
      dosed either separately (SOY: 2.83 mg daidzein aglycone equivalents/supplement,
      HOP: 1.20 mg isoxanthohumol (IX)/supplement, or FLAX: 2.08 mg
      secoisolariciresinol (SECO) aglycone equivalents/supplement; reference
      intervention) or simultaneously (MIX; test intervention) 3 times/d for 5 d,
      followed by a wash-out period (>or=7 d) and the second intervention. Before and
      after each (co)supplementation, spot urine and serum were collected. In total, 22
      equol, 19 8-prenylnaringenin (8-PN), and 21 enterolactone (ENL) producers
      completed the SOY+MIX, HOP+MIX, and FLAX+MIX trials, respectively. The microbial
      bioactivation of daidzein, IX, and SECO, generally decreased upon coincubation in
      vitro (equol: 4.4%, P = 0.164; 8-PN: 20.5%, P < 0.001; ENL: 44.3%, P < 0.001) and
      cosupplementation in vivo (equol: 28.3%, P = 0.009; 8-PN: 35.4%, P = 0.107; ENL:
      35.9%, P = 0.003). Although the bioavailabilities of total isoflavones,
      prenylflavonoids, and lignans were not significantly affected upon
      coadministration, participants were exposed to lower phytoestrogen-derived 17beta
      estradiol equivalents. In conclusion, the bioavailability of phytoestrogens,
      especially when given in mixtures, is subject to high interindividual variation.
      These findings support the importance of personalized screening when assessing
      the efficacy of such products and mixtures.

PMID- 19864399
TI  - A new dietary inflammatory index predicts interval changes in serum high
      sensitivity C-reactive protein.
AB  - Inflammation is associated with a number of chronic conditions, such as cancer
      and cardiovascular disease. Reducing inflammation may help prevent or treat these
      conditions. Diet has consistently been shown to modulate inflammation. To
      facilitate research into the inflammatory effect of diet on health in humans, we
      sought to develop and validate an Inflammatory Index designed to assess the
      inflammatory potential of individuals' diets. An Inflammatory Index was developed
      based on the results of an extensive literature search. Using data from a
      longitudinal observational study that carefully measured diet and the
      inflammatory marker, serum high-sensitivity (hs) C-reactive protein (CRP), in
      approximately 600 adults for 1 y, we conducted analyses to test the effect of
      Inflammatory Index score on hs-CRP as a continuous and dichotomous (<or=3 mg/L,
      >3 mg/L) indicator of inflammatory response, while controlling for important
      potential confounders. Results based on continuous measures of hs-CRP suggested
      that an increasing Inflammatory Index score (representing movement toward an
      antiinflammatory diet) was associated with a decrease in hs-CRP. Analyses using
      hs-CRP as a dichotomous variable showed that an antiinflammatory diet was
      associated with a decrease in the odds of an elevated hs-CRP (P = 0.049). The
      results are consistent with the ability of the Inflammatory Index to predict hs
      CRP and provide additional evidence that diet plays a role in the regulation of
      inflammation, even after careful control of a wide variety of potential
      confounders.

PMID- 19864400
TI  - Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1
      murine mammary carcinoma cells in BALB/c mice.
AB  - 3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed
      oligomerization of indole-3-carbinol present in cruciferous vegetables, and it
      has been shown to exhibit anticancer properties. In this study, we assessed the
      effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro
      culture studies showed that DIM dose-dependently inhibited the migration,
      invasion, and adhesion of 4T1 cells at concentrations of 0-10 micromol/L without
      attendant changes in cell viability. In an in vivo lung metastasis model, 4T1
      cells (2 x 10(5) cells/mouse) were injected into the tail veins of syngeneic
      female BALB/c mice. Beginning on the second day, the mice were subjected to
      gavage with 0-10 mg DIM/(kg body weight x d) for 13 d. Oral DIM administration
      resulted in a marked reduction in the number of pulmonary tumor nodules. DIM
      treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2,
      MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion
      molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice
      injected with 4T1 cells. Additionally, DIM treatment reduced the serum
      concentrations of interleukin (IL)-1beta, IL-6 and tumor necrosis factor
      (TNF)alpha. We have demonstrated that DIM profoundly inhibits the lung metastasis
      of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules,
      and proinflammatory cytokines. These results indicate that DIM has potential as
      an antimetastatic agent for the treatment of breast cancer.

PMID- 19864401
TI  - Dietary arachidonic acid to EPA and DHA balance is increased among Canadian
      pregnant women with low fish intake.
AB  - Arachidonic [ARA, 20:4(n-6)], eicosapentaenoic [EPA, 20:5(n-3)], and
      docosahexaenoic acids [DHA, 22:6(n-3)] occur in the diet in animal tissue lipids,
      play important roles in human development and health, but have interactive and
      opposing functions. Meat and poultry have higher ARA and fish are richer in EPA
      and DHA. National databases were recently revised to include complete data on ARA
      in foods. We used a validated FFQ and the revised nutrient databases to quantify
      the distribution of ARA, EPA, and DHA intakes and balance for 204 healthy
      Canadian pregnant women. We focused on intake distributions because risk of
      adverse health effects increases at lower nutrient intakes. RBC fatty acids were
      analyzed concurrenly with dietary assessment. The distribution of ARA, EPA, and
      DHA intakes were skewed (P < 0.001), with a median (5-95th percentile) of 107 (41
      225), 65 (10-228), and 105 (10-430) mg/d ARA, EPA, and DHA, respectively. Fish
      provided 66 and 76% of EPA and DHA, respectively, whereas eggs, poultry, and
      meats provided 81% of ARA. Women consuming <101 g fish/wk consumed less EPA and
      DHA and had markedly elevated median dietary ARA:EPA and ARA:DHA ratios and RBC
      lipid ARA:EPA + DHA ratios compared with women consuming >or=101 g fish/wk (P <
      0.001). Relatively small increases in fish intake of 1-2 servings (25-50 g)/wk
      corrected the distorted dietary (n-6):(n-3) fatty acid balance among women
      consuming meats, but not fish. Median fish and DHA intakes below the recommended
      1-2 servings/wk fish for pregnant women suggest major changes in the
      availability, cost, or acceptance of fish are needed.

PMID- 19864402
TI  - Single-protein casein and gelatin diets affect energy expenditure similarly but
      substrate balance and appetite differently in adults.
AB  - Increasing the protein content of a diet results in increased satiety and energy
      expenditure (EE). It is not clear whether the magnitude of these effects differs
      between proteins differing in concentrations of indispensable amino acids (IAA).
      We hypothesized that a protein lacking IAA may stimulate appetite suppression and
      EE and may limit positive protein balance. Therefore, we compared appetite, EE,
      and substrate balances between gelatin (incomplete protein) and casein (complete
      protein) in single-protein diets with either 25 or 10% of energy (En%) from
      protein. During a 36-h stay in a respiration chamber, 23 healthy men (n = 11) and
      women (n = 12) (BMI, 22.2 +/- 2.3 kg/m(2); age, 25 +/- 7 y) consumed 4
      isoenergetic diets: 25 En% (25/20/55 En% protein/fat/carbohydrate) and 10 En%
      (10/35/55 En% protein/fat/carbohydrate) casein or gelatin diet in a randomized
      crossover design. For 3 d before the study, participants consumed a diet at home
      with similar macronutrient distribution as the diet they would receive during the
      subsequent stay in the chamber. Hunger was suppressed 44% more (P < 0.05) and
      protein balance was more negative when consuming the 10 En% gelatin diet (-0.17
      +/- 0.03 MJ/d) compared with the 10 En% casein diet (-0.07 +/- 0.03 MJ/d; P <
      0.05); carbohydrate and fat balances did not differ between the treatments. EE
      did not differ when participants consumed the 25 En% or 10 En% diets.
      Participants were in higher protein balance (0.56 +/- 0.05 vs. 0.30 +/- 0.04
      MJ/d; P < 0.0001), lower carbohydrate balance (0.86 +/- 0.14 vs. 1.37 +/- 0.17
      MJ/d; P < 0.01), and similar negative fat balance when they consumed the 25 En%
      casein compared with the 25 En% gelatin diet. In conclusion, when we compared the
      effects of an incomplete protein (gelatin) and a complete protein (casein) at 2
      concentrations over 36 h, gelatin resulted in a greater appetite suppression;
      casein caused a greater positive (smaller negative) protein balance, and effects
      on EE did not differ. In terms of weight loss for people with obesity, the
      greater hunger-suppressing effect of gelatin may play a role in reducing energy
      intake if this effect is maintained when consuming a gelatin diet in the long
      term. In addition, long-term use of casein may contribute to preservation of fat
      free mass.

PMID- 19864403
TI  - Dietary fish oil exerts hypolipidemic effects in lean and insulin sensitizing
      effects in obese LDLR-/- mice.
AB  - Obesity is often associated with dyslipidemia, insulin resistance, and
      hypertension. Together, these metabolic perturbations greatly increase the risk
      of developing cardiovascular disease and diabetes. Although fish oil is a well
      established hypolipidemic agent, the mechanisms by which it mediates its lipid
      lowering effects are not clear. In addition, it has not been established whether
      dietary fish oil has different effects in lean and obese mice. LDL receptor
      deficient (LDLR-/-) and leptin deficient mice on a LDLR-/- background (ob/ob;LDLR
      /-) were fed a high fat diet (39% total fat) supplemented with 6% olive oil or
      fish oil for 6 wk. Fish oil supplementation resulted in lower concentrations of
      plasma total cholesterol (P < 0.01), triglycerides (P < 0.01), and free fatty
      acids (P < 0.001) in lean LDLR-/- mice, but not in ob/ob;LDLR-/- mice. In
      contrast, a fish oil diet did not modulate insulin sensitivity in lean LDLR-/-
      mice, but it improved insulin sensitivity in ob/ob;LDLR-/- mice (P < 0.05)
      compared with olive oil fed ob/ob;LDLR-/- mice. Interestingly, plasma adiponectin
      concentrations were significantly higher and hepatic steatosis was reduced in
      both mouse models upon fish oil feeding. Finally, fish oil fed LDLR-/- mice
      exhibited higher hepatic AMP activated protein kinase (AMPK) phosphorylation (P <
      0.05), whereas AMPK phosphorylation was not elevated by fish oil feeding in
      ob/ob;LDLR-/- mice. Taken together, our data suggest that fish oil reduces
      hepatic steatosis in both lean and obese mice, has potent plasma lipid lowering
      effects in lean mice, and exerts insulin sensitizing effects in obese mice.

PMID- 19864404
TI  - Eating out of home in Vietnamese adolescents: socioeconomic factors and dietary
      associations.
AB  - BACKGROUND: Out-of-home (OH) eating in developed countries is associated with
      suboptimal dietary intakes, but evidence is scarce on the situation in developing
      countries. OBJECTIVE: The objective of this study was to determine the
      nutritional contribution of OH eating and related socioeconomic determinants in
      Vietnamese adolescents. DESIGN: A 24-h recall was used to collect food intake
      data in a cross-sectional study of 1172 adolescents living in urban and rural
      areas. Multilevel analysis compared the mean daily intakes of energy, energy
      density, energy from fat, food groups, vitamin A, iron, and zinc in low, middle,
      and high consumers of OH food. Socioeconomic associations of OH eating were
      analyzed in a subsample of 870 adolescents. RESULTS: OH foods contributed 42% of
      fruit and vegetables, 23% of sodium, 21% of energy, 21% of vitamin A, 21% of
      iron, and 21% of zinc consumed per day. OH eating was negatively associated with
      total energy intake and energy density and positively associated with dietary
      diversity, energy contribution from fat, and consumption of sugar products. In
      rural areas, OH eating was positively associated with iron, fruit, meat, poultry,
      and offal intake. Female sex (P < 0.001), residence in urban areas (P < 0.001),
      and amount of pocket money (P < 0.001) were positively associated with
      consumption of OH foods. CONCLUSIONS: OH eating added a number of desirable foods
      and nutrients but was also associated with higher consumption of energy from fat
      and sugar products. Independent of household wealth and locality, pocket money
      and sex are important determinants of OH eating.

PMID- 19864406
TI  - Dietary protein and bone: a new approach to an old question.

PMID- 19864405
TI  - Longitudinal study of muscle strength, quality, and adipose tissue infiltration.
AB  - BACKGROUND: Sarcopenia is thought to be accompanied by increased muscle fat
      infiltration. However, no longitudinal studies have examined concomitant changes
      in muscle mass, strength, or fat infiltration in older adults. OBJECTIVE: We
      present longitudinal data on age-related changes in leg composition, strength,
      and muscle quality (MQ) in ambulatory, well-functioning men and women. We
      hypothesized that muscle cross-sectional area (CSA) and strength would decrease
      and muscular fat infiltration would increase over 5 y. DESIGN: Midthigh muscle,
      subcutaneous fat (SF), and intermuscular fat (IMF) CSAs and isokinetic leg muscle
      torque (MT) and MQ (MT/quadriceps CSA) were examined over 5 y in the Health,
      Aging, and Body Composition study cohort (n = 1678). RESULTS: Men experienced a
      16.1% loss of MT, whereas women experienced a 13.4% loss. Adjusted annualized
      decreases in MT were 2-5 times greater than the loss of muscle CSA in those who
      lost weight and in those who remained weight-stable. Weight gain did not prevent
      the loss of MT, despite a small increase in muscle CSA. Only those who gained
      weight had an increase in SF (P < 0.001), whereas those who lost weight also lost
      SF (P < 0.001). There was an age-related increase in IMF in men and women (P <
      0.001), and IMF increased in those who lost weight, gained weight, or remained
      weight-stable (all P < 0.001). CONCLUSIONS: Loss of leg MT in older adults is
      greater than muscle CSA loss, which suggests a decrease in MQ. Additionally,
      aging is associated with an increase in IMF regardless of changes in weight or
      SF.

PMID- 19864407
TI  - Effects of TCF7L2 polymorphisms on glucose values after a lifestyle intervention.
AB  - BACKGROUND: TCF7L2 is the strongest locus linked to type 2 diabetes that has been
      identified thus far, and rs7903146 is the most significantly associated variant.
      Few intervention studies have shown that it has negative effects on metabolic
      improvement after lifestyle programs. OBJECTIVE: Our objective was to assess the
      effects of this variant on lifestyle intervention-induced changes in glucose
      values and metabolic variables at 1- and 4-y follow-ups. DESIGN: The rs7903146
      variant was genotyped in 335 nondiabetic, dysmetabolic participants in a
      randomized lifestyle intervention trial. RESULTS: Subjects with the unfavorable
      TT genotype showed higher values of fasting glucose and lower homeostasis model
      assessment of beta cell function at baseline. Lifestyle modifications were
      successful in the amelioration of metabolic traits in all genetic subgroups after
      1 y. At 4-y follow-up most of the metabolic benefits had disappeared. In a
      multiple regression model, values for glucose and homeostasis model assessment of
      beta cell function at 4 y were significantly associated with the T allele (for
      glucose and homeostasis model assessments, respectively: beta = 6.6; 95% CI: 2.5,
      10.7; P = 0.001; and beta = -0.37; 95% CI: -0.54, -0.20; P < 0.001) but not with
      intervention. There was no interaction between genotype and intervention. After 1
      y, impaired fasting glucose and diabetes incidence were inversely associated with
      intervention. After 4 y, the presence of a T allele was associated with impaired
      fasting glucose (odds ratio: 3.04; 95% CI: 1.53, 6.04; P = 0.001) and diabetes
      (odds ratio: 2.63; 95% CI: 1.00, 6.96; P = 0.05) but not with intervention.
      CONCLUSIONS: Lifestyle modifications improved the metabolic pattern in all
      genetic subgroups. At the end of the trial, however, weight gain occurred, and
      carriers of the T allele developed first hyperglycemia and decreased insulin
      secretion, which suggests the need for different "after-care" preventive
      approaches tailored to each genotype's metabolic risk.

PMID- 19864408
TI  - Effects of a prolonged standardized diet on normalizing the human metabolome.
AB  - BACKGROUND: Although the effects of acute dietary interventions on the human
      metabolome have been studied, the extent to which the metabolome can be
      normalized by extended dietary standardization has not yet been examined.
      OBJECTIVE: We examined the metabolic profiles of healthy human subjects after
      extended dietary standardization to see whether the inherent variation in the
      human metabolome could be decreased. DESIGN: A cohort of 10 healthy volunteers
      was admitted to a clinical research center for 2 wk of dietary standardization.
      Daily serum and urine samples and serum samples at a 2-wk follow-up visit were
      collected. The samples were analyzed by (1)H nuclear magnetic resonance (NMR)
      spectroscopy and multivariate statistical analyses. RESULTS: NMR spectra were
      collected to globally profile the higher-concentration metabolites (>micromol/L
      concentrations). Metabolic changes were observed in some serum samples after day
      1 or the 2-wk follow-up visit. For each subject, the samples from all other days
      had similar profiles. The urinary metabolome reflected no effects from dietary
      standardization. Pooled 24-h urine samples were studied, which indicated that any
      normalization that does occur would do so in <24 h. CONCLUSIONS: For both the
      urinary and serum metabolome, a single day of dietary standardization appears to
      provide all of the normalization that is achievable within the strict controls
      implemented in a clinical research setting. After 24 h, the subjects remain in
      their metabolic space; the remaining intra- and intersubject variations appear to
      be influenced by variables such as genetics, age, and lifestyle.

PMID- 19864409
TI  - A randomized trial on folic acid supplementation and risk of recurrent colorectal
      adenoma.
AB  - BACKGROUND: Evidence from observational studies suggests that inadequate folate
      status enhances colorectal carcinogenesis, but results from some randomized
      trials do not support this hypothesis. OBJECTIVE: To assess the effect of folic
      acid supplementation on recurrent colorectal adenoma, we conducted a cost
      efficient, double-blind, randomized trial among participants of 2 large
      prospective cohorts, the Health Professionals Follow-Up Study and the Nurses'
      Health Study. DESIGN: Participants were randomly assigned to receive folic acid
      (1 mg/d) (n = 338) or placebo (n = 334) for 3-6.5 y. The primary endpoint was any
      new diagnosis of adenoma during the study period (May 1996-March 2004). Secondary
      outcomes were adenoma by site and stage and number of recurrent adenomas.
      Associations were also examined by plasma folate concentrations at baseline.
      RESULTS: Incidence of at least one recurrent adenoma was not significantly
      associated with folic acid supplementation [relative risk (RR): 0.82; 95% CI:
      0.59,1.13; P = 0.22]. Among participants with low plasma folate concentrations at
      baseline (<or=7.5 ng/mL), those randomly assigned to receive folic acid
      experienced a significant decrease in adenoma recurrence (RR: 0.61; 95% CI: 0.42,
      0.90; P = 0.01), whereas for subjects with high folate concentrations at baseline
      (>7.5 ng/mL), supplemental folic acid had no significant effect (RR: 1.28; 95%
      CI: 0.82, 1.99; P = 0.27, P(interaction) = 0.01). Contrary to findings from
      another clinical trial, there was no evidence for an increased risk of advanced
      or multiple adenomas. CONCLUSIONS: Our results do not support an overall
      protective effect of folic acid supplementation on adenoma recurrence. Folic acid
      supplementation may be beneficial among those with lower folate concentrations at
      baseline. This trial was registered at clinical trials.gov as NCT00512850.

PMID- 19864410
TI  - Relation between stable isotope ratios in human red blood cells and hair:
      implications for using the nitrogen isotope ratio of hair as a biomarker of
      eicosapentaenoic acid and docosahexaenoic acid.
AB  - BACKGROUND: The nitrogen isotope ratio (expressed as delta(15)N) of red blood
      cells (RBCs) is highly correlated with the RBC long-chain omega-3 (n-3) fatty
      acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in Yup'ik
      Eskimos. Because delta(15)N can also be measured in hair samples, it could
      provide a noninvasive, retrospective biomarker for EPA and DHA intakes.
      OBJECTIVES: We investigated the agreement between delta(15)N in hair and RBCs and
      then evaluated the relations between hair delta(15)N and RBC EPA and DHA. We also
      assessed the agreement in carbon isotope ratios (delta(13)C) between hair and
      RBCs, because delta(13)C has been proposed as a dietary biomarker in other
      populations. DESIGN: We assessed relations between hair and RBC delta(15)N and
      delta(13)C in a community-based sample of 144 Yup'ik Eskimos and examined the
      correlations between delta(15)N and RBC EPA and DHA in a subset of these
      participants (n = 44). RESULTS: We showed a 1:1 relation with good agreement
      between hair and RBC delta(15)N (r = 0.91) and delta(13)C (r = 0.87). Hair
      isotope ratios were greater than RBC ratios by 1.5 per thousand for delta(15)N
      and by 2.3 per thousand for delta(13)C. There were strong correlations between
      hair delta(15)N and RBC EPA and DHA (r = 0.83 and 0.84, respectively).
      CONCLUSIONS: These results support the use of hair delta(15)N values as a
      biomarker of EPA and DHA intakes. Because hair collection is noninvasive and the
      samples require no special processing, studies of EPA and DHA intakes in large
      populations could use biomarkers rather than self-reports to assess these fatty
      acids.

PMID- 19864411
TI  - Use of multivitamin supplements in relation to allergic disease in 8-y-old
      children.
AB  - BACKGROUND: Multivitamins are frequently consumed by children, but it is unclear
      whether this affects the risk of allergic disease. OBJECTIVE: We sought to study
      the association between multivitamin supplementation and allergic disease in 8-y
      old children. DESIGN: Data were obtained from a Swedish birth cohort study.
      Information on lifestyle factors, including use of vitamin supplements,
      environmental exposures, and symptoms and diagnoses of allergic diseases, was
      obtained by parental questionnaires. In addition, allergen-specific IgE
      concentrations of food and airborne allergens were measured in blood samples
      collected at age 8 y. A total of 2423 children were included in the study. The
      association between use of vitamin supplements and the selected health outcomes
      was analyzed with logistic regression. RESULTS: Overall, no strong and consistent
      associations were observed between current multivitamin use and asthma, allergic
      rhinitis, eczema, or atopic sensitization at age 8 y. However, children who
      reported that they started taking multivitamins before or at age 4 y had a
      decreased risk of sensitization to food allergens (odds ratio: 0.61; 95% CI:
      0.39, 0.97) and tendencies toward inverse associations with allergic rhinitis. In
      contrast, there was no consistent association among children who started to use
      multivitamins at or after age 5 y. CONCLUSION: Our results show no association
      between current use of multivitamins and risk of allergic disease but suggest
      that supplementation with multivitamins during the first years of life may reduce
      the risk of allergic disease at school age.

PMID- 19864412
TI  - Adolescent beverage habits and changes in weight over time: findings from Project
      EAT.
AB  - BACKGROUND: Obesity in adolescence has been increasing in the past several
      decades. Beverage habits among adolescents include increased consumption of sugar
      sweetened beverages and decreased consumption of milk. OBJECTIVE: This study
      aimed to examine the association between beverage consumption and 5-y body weight
      change in 2294 adolescents. DESIGN: Project EAT (Eating Among Teens) is a 5-y
      longitudinal study of eating patterns among adolescents. Surveys were completed
      in 1998-1999 (time 1) and in 2003-2004 (time 2). Multivariable linear regression
      was used to examine the association between beverage consumption at time 2 and
      change in body mass index from time 1 to time 2, with adjustments for age,
      socioeconomic status, race, cohort, physical activity, sedentary behavior,
      coffee, tea, time 1 body mass index, and beverage variables. RESULTS: In
      prospective analyses, consumption of beverages was not associated with weight
      gain, except for consumption of low-calorie soft drinks (positive association, P
      = 0.002) and white milk (inverse association, P = 0.03), but these associations
      did not appear to be a monotonic linear dose-response relation. The positive
      association with low-calorie soft drinks was no longer present after adjustment
      for dieting and parental weight-related concerns, which suggests that the use of
      low-calorie soft drinks is a marker for more general dietary behaviors and weight
      concerns. CONCLUSIONS: We showed no association between sugar-sweetened beverage
      consumption, juice consumption, and adolescent weight gain over a 5-y period. A
      direct association between diet beverages and weight gain appeared to be
      explained by dieting practices. Adolescents who consumed little or no white milk
      gained significantly more weight than their peers who consumed white milk. Future
      research that examines beverage habits and weight among adolescents should
      address portion sizes, adolescent maturation, and dieting behaviors.

PMID- 19864413
TI  - Alcadein cleavages by amyloid beta-precursor protein (APP) alpha- and gamma
      secretases generate small peptides, p3-Alcs, indicating Alzheimer disease-related
      gamma-secretase dysfunction.
AB  - Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins,
      designated Alc(alpha), Alc(beta), and Alc(gamma). The Alcs express in neurons
      dominantly and largely colocalize with the Alzheimer amyloid precursor protein
      (APP) in the brain. Alcs and APP show an identical function as a cargo receptor
      of kinesin-1. Moreover, proteolytic processing of Alc proteins appears highly
      similar to that of APP. We found that APP alpha-secretases ADAM 10 and ADAM 17
      primarily cleave Alc proteins and trigger the subsequent secondary
      intramembranous cleavage of Alc C-terminal fragments by a presenilin-dependent
      gamma-secretase complex, thereby generating "APP p3-like" and non-aggregative Alc
      peptides (p3-Alcs). We determined the complete amino acid sequence of p3
      Alc(alpha), p3-Alc(beta), and p3-Alc(gamma), whose major species comprise 35, 37,
      and 31 amino acids, respectively, in human cerebrospinal fluid. We demonstrate
      here that variant p3-Alc C termini are modulated by FAD-linked presenilin 1
      mutations increasing minor beta-amyloid species Abeta42, and these mutations
      alter the level of minor p3-Alc species. However, the magnitudes of C-terminal
      alteration of p3-Alc(alpha), p3-Alc(beta), and p3-Alc(gamma) were not equivalent,
      suggesting that one type of gamma-secretase dysfunction does not appear in the
      phenotype equivalently in the cleavage of type I membrane proteins. Because these
      C-terminal alterations are detectable in human cerebrospinal fluid, the use of a
      substrate panel, including Alcs and APP, may be effective to detect gamma
      secretase dysfunction in the prepathogenic state of Alzheimer disease subjects.

PMID- 19864414
TI  - Heme ligand binding properties and intradimer interactions in the full-length
      sensor protein dos from Escherichia coli and its isolated heme domain.
AB  - Dos from Escherichia coli is a bacterial gas sensor protein comprising a heme
      containing gas sensor domain and a phosphodiesterase catalytic domain. Using a
      combination of static light scattering and gel filtration experiments, we
      established that, as are many other sensor proteins, the full-length protein is
      dimeric. The full-length dimer (association constant <10 nm) is more stable than
      the dimeric heme domain (association constant approximately 1 mum), and the dimer
      interface presumably includes both sensor and catalytic domains. Ultrafast
      spectroscopic studies showed little influence of the catalytic domain on kinetic
      processes in the direct vicinity of the heme. By contrast, the properties of
      ligand (CO and O(2)) binding to the heme in the sensor domain, occurring on a
      microsecond to second time scale, were found to be influenced by (i) the presence
      of the catalytic domain, (ii) the dimerization state, and in dimers, (iii) the
      ligation state of the other subunit. These results imply allosteric interactions
      within dimers. Steady-state titrations demonstrated marked cooperativity in
      oxygen binding to both the full-length protein and the isolated heme domain, a
      feature not reported to date for any dimeric sensor protein. Analysis of a
      variety of time-resolved experiments showed that Met-95 plays a major role in the
      intradimer interactions. The intrinsic binding and dissociation rates of Met-95
      to the heme were modulated approximately 10-fold by intradimer and sensor
      catalytic domain interactions. Dimerization effects were also observed for
      cyanide binding to the ferric heme domains, suggesting a similar role for Met-95
      in ferric proteins.

PMID- 19864415
TI  - A novel xylosylphosphotransferase activity discovered in Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a fungal pathogen that causes serious disease in
      immunocompromised individuals. The organism produces a distinctive polysaccharide
      capsule that is necessary for its virulence, a predominantly polysaccharide cell
      wall, and a variety of protein- and lipid-linked glycans. The glycan synthetic
      pathways of this pathogen are of great interest. Here we report the detection of
      a novel glycosylphosphotransferase activity in C. neoformans, identification of
      the corresponding gene, and characterization of the encoded protein. The observed
      activity is specific for UDP-xylose as a donor and for mannose acceptors and
      forms a xylose-alpha-1-phosphate-6-mannose linkage. This is the first report of a
      xylosylphosphotransferase activity in any system.

PMID- 19864416
TI  - Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor
      of mucolipin-1.
AB  - Loss of function mutations in mucolipin-1 (MCOLN1) have been linked to
      mucolipidosis type IV (MLIV), a recessive lysosomal storage disease characterized
      by severe neurological and ophthalmological abnormalities. MCOLN1 is an ion
      channel that regulates membrane transport along the endolysosomal pathway. It has
      been suggested that MCOLN1 participates in several Ca(2+)-dependent processes,
      including fusion of lysosomes with the plasma membrane, fusion of late endosomes
      and autophagosomes with lysosomes, and lysosomal biogenesis. Here, we searched
      for proteins that interact with MCOLN1 in a Ca(2+)-dependent manner. We found
      that the penta-EF-hand protein ALG-2 binds to the NH-terminal cytosolic tail of
      MCOLN1. The interaction is direct, strictly dependent on Ca(2+), and mediated by
      a patch of charged and hydrophobic residues located between MCOLN1 residues 37
      and 49. We further show that MCOLN1 and ALG-2 co-localize to enlarged endosomes
      induced by overexpression of an ATPase-defective dominant-negative form of Vps4B
      (Vps4B(E235Q)). In agreement with the proposed role of MCOLN1 in the regulation
      of fusion/fission events, we found that overexpression of MCOLN1 caused
      accumulation of enlarged, aberrant endosomes that contain both early and late
      endosome markers. Interestingly, aggregation of abnormal endosomes was greatly
      reduced when the ALG-2-binding domain in MCOLN1 was mutated, suggesting that ALG
      2 regulates MCOLN1 function. Overall, our data provide new insight into the
      molecular mechanisms that regulate MCOLN1 activity. We propose that ALG-2 acts as
      a Ca(2+) sensor that modulates the function of MCOLN1 along the late endosomal
      lysosomal pathway.

PMID- 19864417
TI  - Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase
      kinase (ASK) and stimulates its enzymatic activity.
AB  - Lens epithelium-derived growth factor (LEDGF) is an important co-factor of human
      immunodeficiency virus DNA integration; however, its cellular functions are
      poorly characterized. We now report identification of the Cdc7-activator of S
      phase kinase (ASK) heterodimer as a novel interactor of LEDGF. Both kinase
      subunits co-immunoprecipitated with endogenous LEDGF from human cell extracts.
      Truncation analyses identified the integrase-binding domain of LEDGF as essential
      and minimally sufficient for the interaction with Cdc7-ASK. Reciprocally, the
      interaction required autophosphorylation of the kinase and the presence of 50 C
      terminal residues of ASK. The kinase phosphorylated LEDGF in vitro, with Ser-206
      being the major target, and LEDGF phosphorylated at this residue could be
      detected during S phase of the cell cycle. LEDGF potently stimulated the
      enzymatic activity of Cdc7-ASK, increasing phosphorylation of MCM2 in vitro by
      more than 10-fold. This enzymatic stimulation as well as phosphorylation of LEDGF
      depended on the protein-protein interaction. Intriguingly, removing the C
      terminal region of ASK, involved in the interaction with LEDGF, resulted in a
      hyperactive kinase. Our results indicate that the interaction with LEDGF relieves
      autoinhibition of Cdc7-ASK kinase, imposed by the C terminus of ASK.

PMID- 19864418
TI  - Subunit movements in single membrane-bound H+-ATP synthases from chloroplasts
      during ATP synthesis.
AB  - Subunit movements within the H(+)-ATP synthase from chloroplasts (CF(0)F(1)) are
      investigated during ATP synthesis. The gamma-subunit (gammaCys-322) is covalently
      labeled with a fluorescence donor (ATTO532). A fluorescence acceptor (adenosine
      5'-(beta,gamma-imino)triphosphate (AMPPNP)-ATTO665) is noncovalently bound to a
      noncatalytic site at one alpha-subunit. The labeled CF(0)F(1) is integrated into
      liposomes, and a transmembrane pH difference is generated by an acid base
      transition. Single-pair fluorescence resonance energy transfer is measured in
      freely diffusing proteoliposomes with a confocal two-channel microscope. The
      fluorescence time traces reveal a repetitive three-step rotation of the gamma
      subunit relative to the alpha-subunit during ATP synthesis. Some traces show
      splitting into sublevels with fluctuations between the sublevels. During
      catalysis the central stalk interacts, with equal probability, with each
      alphabeta-pair. Without catalysis the central stalk interacts with only one
      specific alphabeta-pair, and no stepping between FRET levels is observed. Two
      inactive states of the enzyme are identified: one in the presence of AMPPNP and
      one in the presence of ADP.

PMID- 19864419
TI  - HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates
      Sprouty2.
AB  - Sprouty (Spry) proteins are important regulators of receptor tyrosine kinase
      signaling in development and disease. Alterations in cellular Spry content have
      been associated with certain forms of cancers and also in cardiovascular
      diseases. Thus, understanding the mechanisms that regulate cellular Spry levels
      are important. Herein, we demonstrate that Spry1 and Spry2, but not Spry3 or
      Spry4, associate with the HECT domain family E3 ubiquitin ligase, Nedd4. The
      Spry2/Nedd4 association involves the WW domains of Nedd4 and requires
      phosphorylation of the Mnk2 kinase sites, Ser(112) and Ser(121), on Spry2. The
      phospho-Ser(112/121) region on Spry2 that binds WW domains of Nedd4 is a novel
      non-canonical WW domain binding region that does not contain Pro residues after
      phospho-Ser. Endogenous and overexpressed Nedd4 polyubiquitinate Spry2 via
      Lys(48) on ubiquitin and decrease its stability. Silencing of endogenous Nedd4
      increased the cellular Spry2 content and attenuated fibroblast growth factor
      elicited ERK1/2 activation that was reversed when elevations in Spry2 levels were
      prevented by Spry2-specific small interfering RNA. Mnk2 silencing decreased Spry2
      Nedd4 interactions and also augmented the ability of Spry2 to inhibit fibroblast
      growth factor signaling. This is the first report demonstrating the regulation of
      cellular Spry content and its ability to modulate receptor tyrosine kinase
      signaling by a HECT domain-containing E3 ubiquitin ligase.

PMID- 19864420
TI  - A PAS domain binds asparagine in the chemotaxis receptor McpB in Bacillus
      subtilis.
AB  - During chemotaxis toward asparagine by Bacillus subtilis, the ligand is thought
      to bind to the chemoreceptor McpB on the exterior of the cell and induce a
      conformational change. This change affects the degree of phosphorylation of the
      CheA kinase bound to the cytoplasmic region of the receptor. Until recently, the
      sensing domains of the B. subtilis receptors were thought to be structurally
      similar to the well studied Escherichia coli four-helical bundle. However,
      sequence analysis has shown the sensing domains of receptors from these two
      organisms to be vastly different. Homology modeling of the sensing domain of the
      B. subtilis asparagine receptor McpB revealed two tandem PAS domains. McpB
      mutants having alanine substitutions in key arginine and tyrosine residues of the
      upper PAS domain but not in any residues of the lower PAS domain exhibited a
      chemotactic defect in both swarm plates and capillary assays. Thus, binding does
      not appear to occur across any dimeric surface but within a monomer. A modified
      capillary assay designed to determine the concentration of attractant where
      chemotaxis is most sensitive showed that when Arg-111, Tyr-121, or Tyr-133 is
      mutated to an alanine, much more asparagine is required to obtain an active
      chemoreceptor. Isothermal titration calorimetry experiments on the purified
      sensing domain showed a K(D) to asparagine of 14 mum, with the three mutations
      leading to less efficient binding. Taken together, these results reveal not only
      a novel chemoreceptor sensing domain architecture but also, possibly, a different
      mechanism for chemoreceptor activation.

PMID- 19864421
TI  - IcmF is a fusion between the radical B12 enzyme isobutyryl-CoA mutase and its G
      protein chaperone.
AB  - Coenzyme B(12) is used by two highly similar radical enzymes, which catalyze
      carbon skeleton rearrangements, methylmalonyl-CoA mutase and isobutyryl-CoA
      mutase (ICM). ICM catalyzes the reversible interconversion of isobutyryl-CoA and
      n-butyryl-CoA and exists as a heterotetramer. In this study, we have identified
      >70 bacterial proteins, which represent fusions between the subunits of ICM and a
      P-loop GTPase and are currently misannotated as methylmalonyl-CoA mutases. We
      designate this fusion protein as IcmF (isobutyryl-CoA mutase fused). All IcmFs
      are composed of the following three domains: the N-terminal 5'
      deoxyadenosylcobalamin binding region that is homologous to the small subunit of
      ICM (IcmB), a middle P-loop GTPase domain, and a C-terminal part that is
      homologous to the large subunit of ICM (IcmA). The P-loop GTPase domain has very
      high sequence similarity to the Methylobacterium extorquens MeaB, which is a
      chaperone for methylmalonyl-CoA mutase. We have demonstrated that IcmF is an
      active ICM by cloning, expressing, and purifying the IcmFs from Geobacillus
      kaustophilus, Nocardia farcinica, and Burkholderia xenovorans. This finding
      expands the known distribution of ICM activity well beyond the genus
      Streptomyces, where it is involved in polyketides biosynthesis, and suggests a
      role for this enzyme in novel bacterial pathways for amino acid degradation,
      myxalamid biosynthesis, and acetyl-CoA assimilation.

PMID- 19864422
TI  - Human ISCA1 interacts with IOP1/NARFL and functions in both cytosolic and
      mitochondrial iron-sulfur protein biogenesis.
AB  - Iron-sulfur proteins play an essential role in many biologic processes. Hence,
      understanding their assembly is an important goal. In Escherichia coli, the
      protein IscA is a product of the isc (iron-sulfur cluster) operon and functions
      in the iron-sulfur cluster assembly pathway in this organism. IscA is conserved
      in evolution, but its function in mammalian cells is not known. Here, we provide
      evidence for a role for a human homologue of IscA, named IscA1, in iron-sulfur
      protein biogenesis. We observe that small interfering RNA knockdown of IscA1 in
      HeLa cells leads to decreased activity of two mitochondrial iron-sulfur enzymes,
      succinate dehydrogenase and mitochondrial aconitase, as well as a cytosolic iron
      sulfur enzyme, cytosolic aconitase. IscA1 is observed both in cytosolic and
      mitochondrial fractions. We find that IscA1 interacts with IOP1 (iron-only
      hydrogenase-like protein 1)/NARFL (nuclear prelamin A recognition factor-like), a
      cytosolic protein that plays a role in the cytosolic iron-sulfur protein assembly
      pathway. We therefore propose that human IscA1 plays an important role in both
      mitochondrial and cytosolic iron-sulfur cluster biogenesis, and a notable
      component of the latter is the interaction between IscA1 and IOP1.

PMID- 19864423
TI  - Catalytic mechanism of S-type phycobiliprotein lyase: chaperone-like action and
      functional amino acid residues.
AB  - The phycobilin:cysteine 84-phycobiliprotein lyase, CpcS1, catalyzes
      phycocyanobilin (PCB) and phycoerythrobilin (PEB) attachment at nearly all
      cysteine 82 binding sites (consensus numbering) of phycoerythrin,
      phycoerythrocyanin, phycocyanin, and allophycocyanin (Zhao, K. H., Su, P., Tu, J.
      M., Wang, X., Liu, H., Ploscher, M., Eichacker, L., Yang, B., Zhou, M., and
      Scheer, H. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 14300-14305). We now show
      that CpcS1 binds PCB and PEB rapidly with bi-exponential kinetics (38/119 and
      12/8300 ms, respectively). Chromophore binding to the lyase is reversible and
      much faster than the spontaneous, but low fidelity chromophore addition to the
      apo-protein in the absence of the lyase. This indicates kinetic control by the
      enzyme, which then transfers the chromophore to the apo-protein in a slow (tens
      of minutes) but stereo- and regioselectively corrects the reaction. This mode of
      action is reminiscent of chaperones but does not require ATP. The amino acid
      residues Arg-18 and Arg-149 of the lyase are essential for chromophore attachment
      in vitro and in Escherichia coli, mutations of His-21, His-22, Trp-75, Trp-140,
      and Arg-147 result in reduced activity (<30% of wild type in vitro). Mutants
      R147Q and W69M were active but had reduced capacity for PCB binding;
      additionally, with W69M there was loss of fidelity in chromophore attachment.
      Imidazole is a non-competitive inhibitor, supporting a bilin-binding function of
      histidine. Evidence was obtained that CpcS1 also catalyzes exchange of C-beta84
      bound PCB in biliproteins by PEB.

PMID- 19864424
TI  - Identification and characterization of unique proline-rich peptides binding to
      the mitochondrial fission protein hFis1.
AB  - Mammalian mitochondrial fission requires at least two proteins, hFis1 and the
      dynamin-like GTPase DLP1/Drp1. The mitochondrial protein hFis1 is anchored at the
      outer membrane by a C-terminal transmembrane domain. The cytosolic domain of
      hFis1 contains six alpha helices [alpha1-alpha6] out of which [alpha2-alpha5]
      form tetratricopeptide repeat (TPR)-like motifs. DLP1 and possibly other proteins
      are thought to interact with the hFis1 TPR region during the fission process. It
      has also been suggested that the alpha1-helix regulates protein-protein
      interactions at the TPR. We performed random peptide phage display screening
      using the hFis1[alpha2-alpha6] as the target and identified ten different peptide
      sequences. Phage ELISA using mutant hFis1 indicates that the peptide binding
      requires the alpha2 and alpha3 helices and the intact TPR structure. Competition
      experiments and surface plasmon resonance analyses confirmed that a subset of
      free peptides enriched with proline residues directly bind to the target. Two of
      these peptides bind to the alpha1-containing intact cytosolic domain of hFis1
      with decreased affinity. Peptide microinjection into cells abolished the
      mitochondrial swelling induced by overexpression of alpha1-deleted hFis1, and
      significantly decreased cytochrome c release from mitochondria upon apoptotic
      induction. Our data demonstrate that hFis1 can bind to multiple amino acid
      sequences selectively, and that the TPR constitutes the main binding region of
      hFis1, providing a first insight into the hFis1 TPR as a potential therapeutic
      target.

PMID- 19864425
TI  - Proteomic analysis of GLUT4 storage vesicles reveals LRP1 to be an important
      vesicle component and target of insulin signaling.
AB  - Insulin stimulates the translocation of intracellular GLUT4 to the plasma
      membrane where it functions in adipose and muscle tissue to clear glucose from
      circulation. The pathway and regulation of GLUT4 trafficking are complicated and
      incompletely understood and are likely to be contingent upon the various proteins
      other than GLUT4 that comprise and interact with GLUT4-containing vesicles.
      Moreover, not all GLUT4 intracellular pools are insulin-responsive as some
      represent precursor compartments, thus posing a biochemical challenge to the
      purification and characterization of their content. To address these issues, we
      immunodepleted precursor GLUT4-rich vesicles and then immunopurified GLUT4
      storage vesicle (GSVs) from primary rat adipocytes and subjected them to semi
      quantitative and quantitative proteomic analysis. The purified vesicles
      translocate to the cell surface almost completely in response to insulin, the
      expected behavior for bona fide GSVs. In total, over 100 proteins were
      identified, about 50 of which are novel in this experimental context. LRP1 (low
      density lipoprotein receptor-related protein 1) was identified as a major
      constituent of GSVs, and we show it interacts with the lumenal domains of GLUT4
      and other GSV constituents. Its cytoplasmic tail interacts with the insulin
      signaling pathway target, AS160 (Akt substrate of 160 kDa). Depletion of LRP1
      from 3T3-L1 adipocytes reduces GLUT4 expression and correspondingly results in
      decreased insulin-stimulated 2-[(3)H]deoxyglucose uptake. Furthermore, adipose
      specific LRP1 knock-out mice also exhibit decreased GLUT4 expression. These
      findings suggest LRP1 is an important component of GSVs, and its expression is
      needed for the formation of fully functional GSVs.

PMID- 19864426
TI  - Structure of the N-terminal regulatory domain of a plant NADPH oxidase and its
      functional implications.
AB  - Plant NADPH oxidases (Rboh, for respiratory burst oxidase homolog) produce
      reactive oxygen species that are key regulators of various cellular events
      including plant innate immunity. Rbohs possess a highly conserved cytoplasmic N
      terminal region containing two EF-hand motifs that regulate Rboh activity. Rice
      (Oryza sativa) RbohB (OsRbohB) is regulated by the direct binding of a small
      GTPase (Rac1) to this regulatory region as well as by Ca(2+) binding to the EF
      hands. Here, we present the atomic structure of the N-terminal region of OsRbohB.
      The structure reveals that OsRbohB forms a unique dimer stabilized by swapping
      the EF-hand motifs. We identified two additional EF-hand-like motifs that were
      not predicted from sequence data so far. These EF-hand-like motifs together with
      the swapped EF-hands form a structure similar to that found in calcineurin B. We
      observed conformational changes mediated by Ca(2+) binding to only one EF-hand.
      Structure-based in vitro pulldown assays and NMR titration experiments defined
      the OsRac1 binding interface within the coiled-coil region created by swapping
      the EF-hands. In addition, we demonstrate a direct intramolecular interaction
      between the N and C terminus, and that the complete N-terminal cytoplasmic region
      is required for this interaction. The structural features and intramolecular
      interactions characterized here might be common elements shared by Rbohs that
      contribute to the regulation of reactive oxygen species production.

PMID- 19864427
TI  - Beta-catenin up-regulates Atoh1 expression in neural progenitor cells by
      interaction with an Atoh1 3' enhancer.
AB  - Atoh1, a basic helix-loop-helix transcription factor, plays a critical role in
      the differentiation of several epithelial and neural cell types. We found that
      beta-catenin, the key mediator of the canonical Wnt pathway, increased expression
      of Atoh1 in mouse neuroblastoma cells and neural progenitor cells, and baseline
      Atoh1 expression was decreased by siRNA directed at beta-catenin. The up
      regulation of Atoh1 was caused by an interaction of beta-catenin with the Atoh1
      enhancer that could be demonstrated by chromatin immunoprecipitation. We found
      that two putative Tcf-Lef sites in the 3' enhancer of the Atoh1 gene displayed an
      affinity for beta-catenin and were critical for the activation of Atoh1
      transcription because mutation of either site decreased expression of a reporter
      gene downstream of the enhancer. Tcf-Lef co-activators were found in the complex
      that bound to these sites in the DNA together with beta-catenin. Inhibition of
      Notch signaling, which has previously been shown to induce bHLH transcription
      factor expression, increased beta-catenin expression in progenitor cells of the
      nervous system. Because this could be a mechanism for up-regulation of Atoh1
      after inhibition of Notch, we tested whether siRNA to beta-catenin prevented the
      increase in Atoh1 and found that beta-catenin expression was required for
      increased expression of Atoh1 after Notch inhibition.

PMID- 19864428
TI  - Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop
      phosphorylation.
AB  - p70 ribosomal S6 kinase (p70S6K) is a downstream effector of the mTOR signaling
      pathway involved in cell proliferation, cell growth, cell-cycle progression, and
      glucose homeostasis. Multiple phosphorylation events within the catalytic,
      autoinhibitory, and hydrophobic motif domains contribute to the regulation of
      p70S6K. We report the crystal structures of the kinase domain of p70S6K1 bound to
      staurosporine in both the unphosphorylated state and in the 3'-phosphoinositide
      dependent kinase-1-phosphorylated state in which Thr-252 of the activation loop
      is phosphorylated. Unphosphorylated p70S6K1 exists in two crystal forms, one in
      which the p70S6K1 kinase domain exists as a monomer and the other as a domain
      swapped dimer. The crystal structure of the partially activated kinase domain
      that is phosphorylated within the activation loop reveals conformational ordering
      of the activation loop that is consistent with a role in activation. The
      structures offer insights into the structural basis of the 3'-phosphoinositide
      dependent kinase-1-induced activation of p70S6K and provide a platform for the
      rational structure-guided design of specific p70S6K inhibitors.

PMID- 19864429
TI  - AF17 competes with AF9 for binding to Dot1a to up-regulate transcription of
      epithelial Na+ channel alpha.
AB  - We previously reported that Dot1a.AF9 complex represses transcription of the
      epithelial Na(+) channel subunit alpha (alpha-ENaC) gene in mouse inner medullary
      collecting duct mIMCD3 cells and mouse kidney. Aldosterone relieves this
      repression by down-regulating the complex through various mechanisms. Whether
      these mechanisms are sufficient and conserved in human cells or can be applied to
      other aldosterone-regulated genes remains largely unknown. Here we demonstrate
      that human embryonic kidney 293T cells express the three ENaC subunits and all of
      the ENaC transcriptional regulators examined. These cells respond to aldosterone
      and display benzamil-sensitive Na(+) currents, as measured by whole-cell patch
      clamping. We also show that AF17 and AF9 competitively bind to the same domain of
      Dot1a in multiple assays and have antagonistic effects on expression of an alpha
      ENaC promoter-luciferase construct. Overexpression of Dot1a or AF9 decreased mRNA
      expression of the ENaC subunits and their transcriptional regulators and reduced
      benzamil-sensitive Na(+) currents. AF17 overexpression caused the opposite
      effects, accompanied by redirection of Dot1a from the nucleus to the cytoplasm
      and reduction in histone H3 K79 methylation. The nuclear export inhibitor
      leptomycin B blocked the effect of AF17 overexpression on H3 K79 hypomethylation.
      RNAi-mediated knockdown of AF17 yielded nuclear enrichment of Dot1a and histone
      H3 K79 hypermethylation. As with AF9, AF17 displays nuclear and cytoplasmic co
      localization with Sgk1. Therefore, AF17 competes with AF9 to bind Dot1a,
      decreases Dot1a nuclear expression by possibly facilitating its nuclear export,
      and relieves Dot1a.AF9-mediated repression of alpha-ENaC and other target genes.

PMID- 19864430
TI  - Glyphosate resistance by engineering the flavoenzyme glycine oxidase.
AB  - Glycine oxidase from Bacillus subtilis is a homotetrameric flavoprotein of great
      potential biotechnological use because it catalyzes the oxidative deamination of
      various amines and d-isomer of amino acids to yield the corresponding alpha-keto
      acids, ammonia/amine, and hydrogen peroxide. Glyphosate (N
      phosphonomethylglycine), a broad spectrum herbicide, is an interesting synthetic
      amino acid: this compound inhibits 5-enolpyruvylshikimate-3-phosphate synthase in
      the shikimate pathway, which is essential for the biosynthesis of aromatic amino
      acids in plants and certain bacteria. In recent years, transgenic crops resistant
      to glyphosate were mainly generated by overproducing the plant enzyme or by
      introducing a 5-enolpyruvylshikimate-3-phosphate synthase insensitive to this
      herbicide. In this work, we propose that the enzymatic oxidation of glyphosate
      could be an effective alternative to this important biotechnological process. To
      reach this goal, we used a rational design approach (together with site
      saturation mutagenesis) to generate a glycine oxidase variant more active on
      glyphosate than on the physiological substrate glycine. The glycine oxidase
      containing three point mutations (G51S/A54R/H244A) reaches an up to a 210-fold
      increase in catalytic efficiency and a 15,000-fold increase in the specificity
      constant (the k(cat)/K(m) ratio between glyphosate and glycine) as compared with
      wild-type glycine oxidase. The inspection of its three-dimensional structure
      shows that the alpha2-alpha3 loop (comprising residues 50-60 and containing two
      of the mutated residues) assumes a novel conformation and that the newly
      introduced residue Arg(54) could be the key residue in stabilizing glyphosate
      binding and destabilizing glycine positioning in the binding site, thus
      increasing efficiency on the herbicide.

PMID- 19864431
TI  - Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite
      phosphorylation.
AB  - The rapamycin-sensitive mTOR complex 1 (mTORC1) promotes protein synthesis, cell
      growth, and cell proliferation in response to growth factors and nutritional
      cues. To elucidate the poorly defined mechanisms underlying mTORC1 regulation, we
      have studied the phosphorylation of raptor, an mTOR-interacting partner. We have
      identified six raptor phosphorylation sites that lie in two centrally localized
      clusters (cluster 1, Ser(696)/Thr(706) and cluster 2,
      Ser(855)/Ser(859)/Ser(863)/Ser(877)) using tandem mass spectrometry and generated
      phosphospecific antibodies for each of these sites. Here we focus primarily
      although not exclusively on raptor Ser(863) phosphorylation. We report that
      insulin promotes mTORC1-associated phosphorylation of raptor Ser(863) via the
      canonical PI3K/TSC/Rheb pathway in a rapamycin-sensitive manner. mTORC1
      activation by other stimuli (e.g. amino acids, epidermal growth factor/MAPK
      signaling, and cellular energy) also promote raptor Ser(863) phosphorylation.
      Rheb overexpression increases phosphorylation on raptor Ser(863) as well as on
      the five other identified sites (e.g. Ser(859), Ser(855), Ser(877), Ser(696), and
      Thr(706)). Strikingly, raptor Ser(863) phosphorylation is absolutely required for
      raptor Ser(859) and Ser(855) phosphorylation. These data suggest that mTORC1
      activation leads to raptor multisite phosphorylation and that raptor Ser(863)
      phosphorylation functions as a master biochemical switch that modulates
      hierarchical raptor phosphorylation (e.g. on Ser(859) and Ser(855)). Importantly,
      mTORC1 containing phosphorylation site-defective raptor exhibits reduced in vitro
      kinase activity toward the substrate 4EBP1, with a multisite raptor 6A mutant
      more strongly defective that single-site raptor S863A. Taken together, these data
      suggest that complex raptor phosphorylation functions as a biochemical rheostat
      that modulates mTORC1 signaling in accordance with environmental cues.

PMID- 19864432
TI  - Differential regulation of TRPV1, TRPV3, and TRPV4 sensitivity through a
      conserved binding site on the ankyrin repeat domain.
AB  - Transient receptor potential vanilloid (TRPV) channels, which include the
      thermosensitive TRPV1-V4, have large cytoplasmic regions flanking the
      transmembrane domain, including an N-terminal ankyrin repeat domain. We show that
      a multiligand binding site for ATP and calmodulin previously identified in the
      TRPV1 ankyrin repeat domain is conserved in TRPV3 and TRPV4, but not TRPV2.
      Accordingly, TRPV2 is insensitive to intracellular ATP, while, as previously
      observed with TRPV1, a sensitizing effect of ATP on TRPV4 required an intact
      binding site. In contrast, ATP reduced TRPV3 sensitivity and potentiation by
      repeated agonist stimulations. Thus, ATP and calmodulin, acting through this
      conserved binding site, are key players in generating the different sensitivity
      and adaptation profiles of TRPV1, TRPV3, and TRPV4. Our results suggest that
      competing interactions of ATP and calmodulin influence channel sensitivity to
      fluctuations in calcium concentration and perhaps even metabolic state. Different
      feedback mechanisms likely arose because of the different physiological stimuli
      or temperature thresholds of these channels.

PMID- 19864433
TI  - Prediction of geometrically feasible three-dimensional structures of
      pseudoknotted RNA through free energy estimation.
AB  - Accurate free energy estimation is essential for RNA structure prediction. The
      widely used Turner's energy model works well for nested structures. For
      pseudoknotted RNAs, however, there is no effective rule for estimation of loop
      entropy and free energy. In this work we present a new free energy estimation
      method, termed the pseudoknot predictor in three-dimensional space (pk3D), which
      goes beyond Turner's model. Our approach treats nested and pseudoknotted
      structures alike in one unifying physical framework, regardless of how complex
      the RNA structures are. We first test the ability of pk3D in selecting native
      structures from a large number of decoys for a set of 43 pseudoknotted RNA
      molecules, with lengths ranging from 23 to 113. We find that pk3D performs
      slightly better than the Dirks and Pierce extension of Turner's rule. We then
      test pk3D for blind secondary structure prediction, and find that pk3D gives the
      best sensitivity and comparable positive predictive value (related to
      specificity) in predicting pseudoknotted RNA secondary structures, when compared
      with other methods. A unique strength of pk3D is that it also generates spatial
      arrangement of structural elements of the RNA molecule. Comparison of three
      dimensional structures predicted by pk3D with the native structure measured by
      nuclear magnetic resonance or X-ray experiments shows that the predicted spatial
      arrangement of stems and loops is often similar to that found in the native
      structure. These close-to-native structures can be used as starting points for
      further refinement to derive accurate three-dimensional structures of RNA
      molecules, including those with pseudoknots.

PMID- 19864434
TI  - CCR2 receptor ligands inhibit Cav3.2 T-type calcium channels.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a cytokine known to be involved in
      the recruitment of monocytes to sites of injury. MCP-1 activates the chemokine (C
      C motif) receptor 2 (CCR2), a seven-transmembrane helix G protein-coupled
      receptor that has been implicated in inflammatory pain responses. Here we show
      that MCP-1 mediates activation of the CCR2 receptor and inhibits coexpressed N
      type calcium channels in tsA-201 cells via a voltage-dependent pathway. Moreover,
      MCP-1 inhibits Ca(v)3.2 calcium channels, but not other members of the Cav3
      calcium channel family, with nanomolar affinity. Unlike in N-type channels, this
      modulation does not require CCR2 receptor activation and seems to involve a
      direct action of the ligand on the channel. Whole-cell T-type calcium currents in
      acutely dissociated dorsal root ganglia neurons are effectively inhibited by MCP
      1, consistent with the notion that these cells express Ca(v)3.2. The effects of
      MCP-1 were eliminated by heat denaturation. Furthermore, they were sensitive to
      the application of the divalent metal ion chelator diethylenetriaminepentaacetic
      acid, suggesting the possibility that metal ions may act as a cofactor. Finally,
      small organic CCR2 receptor antagonists inhibit Ca(v)3.2 and other members of the
      T-type channel family with micromolar affinity. Our findings provide novel
      avenues for the design of small organic inhibitors of T-type calcium channels for
      the treatment of pain and other T-type channel linked disorders.

PMID- 19864435
TI  - Cellular signal transduction of the hypoxia response.
AB  - Cells induce the hypoxia responses to adapt to the environment when organisms are
      exposed to a low oxygen environment. The hypoxia response leads to the activation
      of multiple cellular signalling pathways involved in regulation of respiration,
      metabolism, cell survival and so forth. Hypoxia-Inducible-Factor (HIF) pathway
      plays a central role during the hypoxia response as its expression and activity
      are regulated in an oxygen-dependent manner and it also regulates the expression
      of multiple hypoxia responsive genes. The expression of HIF is regulated by
      proline hydroxylation, which is mediated by HIF prolyl-hydroxylase named PHD. The
      hydroxylated HIF-alpha subunit is degraded via the ubiquitin-proteasome pathway.
      The PHD activity needs to be strictly regulated to ensure the stabilization of
      HIF under hypoxic conditions, because PHD leads to HIF degradation. This review
      describes the regulatory mechanism of HIF stability and activity under normoxia
      and hypoxic conditions. Furthermore, the role of the HIF-independent pathways
      during the hypoxia response, which is as important as the HIF pathway, will also
      be described.

PMID- 19864437
TI  - Behavioral time course of microstimulation in cortical area MT.
AB  - Electrical stimulation of the brain is a valuable research tool and has shown
      therapeutic promise in the development of new sensory neural prosthetics. Despite
      its widespread use, we still do not fully understand how current passed through a
      microelectrode interacts with functioning neural circuits. Past behavioral
      studies have suggested that weak electrical stimulation (referred to as
      microstimulation) of sensory areas of cortex produces percepts that are similar
      to those generated by normal sensory stimuli. In contrast, electrophysiological
      studies using in vitro or anesthetized preparations have shown that neural
      activity produced by brief microstimulation is radically different and longer
      lasting than normal responses. To help reconcile these two aspects of
      microstimulation, we examined the temporal properties that microstimulation has
      on visual perception. We found that brief application of subthreshold
      microstimulation in the middle temporal (MT) area of visual cortex produced
      smaller and longer-lasting effects on motion perception compared with an
      equivalent visual stimulus. In agreement with past electrophysiological studies,
      a computer simulation reproduced our behavioral effects when the time course of a
      single microstimulation pulse was modeled with three components: an immediate
      fast strong excitatory component, followed by a weaker inhibitory component, and
      then followed by a long duration weak excitatory component. Overall, these
      results suggest the behavioral effects of microstimulation in our experiments
      were caused by the unique and long-lasting temporal effects microstimulation has
      on functioning cortical circuits.

PMID- 19864436
TI  - Responses of human medial temporal lobe neurons are modulated by stimulus
      repetition.
AB  - Recent studies have reported the presence of single neurons with strong responses
      to visual inputs in the human medial temporal lobe. Here we show how repeated
      stimulus presentation--photos of celebrities and familiar individuals, landmark
      buildings, animals, and objects--modulates the firing rate of these cells: a
      consistent decrease in the neural activity was registered as images were
      repeatedly shown during experimental sessions. The effect of repeated stimulus
      presentation was not the same for all medial temporal lobe areas. These findings
      are consistent with the view that medial temporal lobe neurons link visual
      percepts to declarative memory.

PMID- 19864438
TI  - Neurons in both pallidal segments change their firing properties similarly prior
      to closure of the eyes.
AB  - Current anatomical models of the cortico-basal ganglia (BG) network predict
      reciprocal discharge patterns between the external and internal segments of the
      globus pallidus (GPe and GPi, respectively), as well as cortical driving of BG
      activity. However, physiological studies revealing similarity in the transient
      responses of GPe and GPi neurons cast doubts on these predictions. Here, we
      studied the discharge properties of GPe, GPi, and primary motor cortex neurons of
      two monkeys in two distinct states: when eyes are open versus when they are
      closed. Both pallidal populations exhibited decreased discharge rates in the "eye
      closed" state accompanied by elevated values of the coefficient of variation (CV)
      of their interspike interval (ISI) distributions. The pallidal modulations in
      discharge patterns were partially attributable to larger fractions of longer ISIs
      in the "eye closed" state. In addition, the pallidal discharge modulations were
      gradual, starting prior to closing of the eyes. Cortical neurons, as opposed to
      pallidal neurons, increased their discharge rates steeply on closure of the eyes.
      Surprisingly, the cortical rate modulations occurred after pallidal modulations.
      However, as in the pallidum, the CV values of cortical ISI distributions
      increased in the "eye closed" state, indicating a more bursty discharge pattern
      in that state. Thus changes in GPe and GPi discharge properties were positively
      correlated, suggesting that the subthalamic nucleus and/or the striatum
      constitute the main common driving force for both pallidal segments. Furthermore,
      the early, unexpected changes in the pallidum are better explained by a
      subcortical rather than a cortical loop through the BG.

PMID- 19864439
TI  - Relationships between the threshold and slope of psychometric and neurometric
      functions during perceptual learning: implications for neuronal pooling.
AB  - Perceptual learning involves long-lasting improvements in the ability to perceive
      simple sensory stimuli. Some forms of perceptual learning are thought to involve
      an increasingly selective readout of sensory neurons that are most sensitive to
      the trained stimulus. Here we report novel changes in the relationship between
      the threshold and slope of the psychometric function during learning that are
      consistent with such changes in readout and can provide insights into the
      underlying neural mechanisms. In monkeys trained on a direction-discrimination
      task, perceptual improvements corresponded to lower psychometric thresholds and
      slightly shallower slopes. However, this relationship between threshold and slope
      was much weaker in comparable, ideal-observer "neurometric" functions of neurons
      in the middle temporal (MT) area, which represent sensory information used to
      perform the task and whose response properties did not change with training. We
      propose a linear/nonlinear pooling scheme to account for these results. According
      to this scheme, MT responses are pooled via linear weights that change with
      training to more selectively read out responses from the most sensitive neurons,
      thereby reducing predicted thresholds. An additional nonlinear (power-law)
      transformation does not change with training and causes the predicted
      psychometric function to become shallower as uninformative neurons are eliminated
      from the pooled signal. We show that this scheme is consistent with the measured
      changes in psychometric threshold and slope throughout training. The results
      suggest that some forms of perceptual learning involve improvements in a process
      akin to selective attention that pools the most informative neural signals to
      guide behavior.

PMID- 19864440
TI  - Laminar diversity of dynamic sound processing in cat primary auditory cortex.
AB  - For primary auditory cortex (AI) laminae, there is little evidence of functional
      specificity despite clearly expressed cellular and connectional differences.
      Natural sounds are dominated by dynamic temporal and spectral modulations and we
      used these properties to evaluate local functional differences or constancies
      across laminae. To examine the layer-specific processing of acoustic modulation
      information, we simultaneously recorded from multiple AI laminae in the
      anesthetized cat. Neurons were challenged with dynamic moving ripple stimuli and
      we subsequently computed spectrotemporal receptive fields (STRFs). From the
      STRFs, temporal and spectral modulation transfer functions (tMTFs, sMTFs) were
      calculated and compared across layers. Temporal and spectral modulation
      properties often differed between layers. On average, layer II/III and VI neurons
      responded to lower temporal modulations than those in layer IV. tMTFs were mainly
      band-pass in granular layer IV and became more low-pass in infragranular layers.
      Compared with layer IV, spectral MTFs were broader and their upper cutoff
      frequencies higher in layers V and VI. In individual penetrations, temporal
      modulation preference was similar across layers for roughly 70% of the
      penetrations, suggesting a common, columnar functional characteristic. By
      contrast, only about 30% of penetrations showed consistent spectral modulation
      preferences across layers, indicative of functional laminar diversity or
      specialization. Since local laminar differences in stimulus preference do not
      always parallel the main flow of information in the columnar cortical
      microcircuit, this indicates the influence of additional horizontal or
      thalamocortical inputs. AI layers that express differing modulation properties
      may serve distinct roles in the extraction of dynamic sound information, with the
      differing information specific to the targeted stations of each layer.

PMID- 19864441
TI  - Where is your arm? Variations in proprioception across space and tasks.
AB  - The sense of limb position is crucial for movement control and environmental
      interactions. Our understanding of this fundamental proprioceptive process,
      however, is limited. For example, little is known about the accuracy of arm
      proprioception: Does it vary with changes in arm configuration, since some
      peripheral receptors are engaged only when joints move toward extreme angles? Are
      these variations consistent across different tasks? Does proprioceptive ability
      change depending on what we try to localize (e.g., fingertip position vs. elbow
      angle)? We used a robot exoskeleton to study proprioception in 14 arm
      configurations across three tasks, asking healthy subjects to 1) match a pointer
      to elbow angles after passive movements, 2) match a pointer to fingertip
      positions after passive movements, and 3) actively match their elbow angle to a
      pointer. Across all three tasks, subjects overestimated more extreme joint
      positions; this may be due to peripheral sensory signals biasing estimates as a
      safety mechanism to prevent injury. We also found that elbow angle estimates were
      more precise when used to judge fingertip position versus directly reported,
      suggesting that the brain has better access to limb endpoint position than joint
      angles. Finally, precision of elbow angle estimates improved in active versus
      passive movements, corroborating work showing that efference copies of motor
      commands and alpha-gamma motor neuron coactivation contribute to proprioceptive
      estimates. In sum, we have uncovered fundamental aspects of normal proprioceptive
      processing, demonstrating not only predictable biases that are dependent on joint
      configuration and independent of task but also improved precision when
      integrating information across joints.

PMID- 19864442
TI  - Role of AMPA and NMDA receptors and back-propagating action potentials in spike
      timing-dependent plasticity.
AB  - The cellular mechanisms that mediate spike timing-dependent plasticity (STDP) are
      largely unknown. We studied in vitro in CA1 pyramidal neurons the contribution of
      AMPA and N-methyl-d-aspartate (NMDA) components of Schaffer collateral (SC)
      excitatory postsynaptic potentials (EPSPs; EPSP(AMPA) and EPSP(NMDA)) and of the
      back-propagating action potential (BAP) to the long-term potentiation (LTP)
      induced by a STDP protocol that consisted in pairing an EPSP and a BAP. Transient
      blockade of EPSP(AMPA) with 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6
      carbonitrile (CNQX) during the STDP protocol prevented LTP. Contrastingly LTP was
      induced under transient inhibition of EPSP(AMPA) by combining SC stimulation, an
      imposed EPSP(AMPA)-like depolarization, and BAP or by coupling the EPSP(NMDA)
      evoked under sustained depolarization (approximately -40 mV) and BAP. In Mg(2+)
      free solution EPSP(NMDA) and BAP also produced LTP. Suppression of EPSP(NMDA) or
      BAP always prevented LTP. Thus activation of NMDA receptors and BAPs are needed
      but not sufficient because AMPA receptor activation is also obligatory for STDP.
      However, a transient depolarization of another origin that unblocks NMDA
      receptors and a BAP may also trigger LTP.

PMID- 19864443
TI  - Development of auditory phase-locked activity for music sounds.
AB  - The auditory cortex undergoes functional and anatomical development that reflects
      specialization for learned sounds. In humans, auditory maturation is evident in
      transient auditory-evoked potentials (AEPs) elicited by speech or music. However,
      neural oscillations at specific frequencies are also known to play an important
      role in perceptual processing. We hypothesized that, if oscillatory activity in
      different frequency bands reflects different aspects of sound processing, the
      development of phase-locking to stimulus attributes at these frequencies may have
      different trajectories. We examined the development of phase-locking of
      oscillatory responses to music sounds and to pure tones matched to the
      fundamental frequency of the music sounds. Phase-locking for theta (4-8 Hz),
      alpha (8-14 Hz), lower-to-mid beta (14-25 Hz), and upper-beta and gamma (25-70
      Hz) bands strengthened with age. Phase-locking in the upper-beta and gamma range
      matured later than in lower frequencies and was stronger for music sounds than
      for pure tones, likely reflecting the maturation of neural networks that code
      spectral complexity. Phase-locking for theta, alpha, and lower-to-mid beta was
      sensitive to temporal onset (rise time) sound characteristics. The data were also
      consistent with phase-locked oscillatory effects of acoustic (spectrotemporal)
      complexity and timbre familiarity. Future studies are called for to evaluate
      developmental trajectories for oscillatory activity, using stimuli selected to
      address hypotheses related to familiarity and spectral and temporal encoding
      suggested by the current findings.

PMID- 19864444
TI  - Influence of parallel and orthogonal real lines on illusory contour perception.
AB  - Real lines and illusory contours (ICs) have been reported to either interfere
      with or facilitate the perception of the other, depending on real line
      orientation and contrast. Here we investigate contextual effects of real lines on
      illusory contour perception. Curvature discrimination thresholds of Kanizsa
      contours were measured for superimposed real lines of different sub- and
      suprathreshold contrasts. We find that parallel lines interfere with curvature
      discrimination at suprathreshold, whereas orthogonal lines interfere at
      subthreshold contrasts. We did not find stable facilitating effects of lines in
      any orientation or contrast. These results are discussed in relation to existing
      physiological and imaging data.

PMID- 19864445
TI  - Laboratory worker knowledge, attitudes and practices towards smallpox vaccine.
AB  - BACKGROUND: Recent cases of laboratory-acquired vaccinia virus (VV) infection
      highlight the need for laboratory safety. AIMS: To determine laboratory worker
      adherence to the Advisory Committee for Immunization Practices smallpox
      vaccination recommendations, assess potential barriers to vaccination and
      determine the influence of training on laboratory worker attitudes. METHODS:
      Ninety-two laboratory workers in Pennsylvania were contacted and asked to
      complete an online survey about VV usage; 45 responded. RESULTS: Eighty-seven per
      cent had received a smallpox vaccination in their lifetime; 73% received
      vaccination in the past 10 years. More workers had been given training regarding
      the potential risks, versus the potential benefits of vaccination, and most
      perceived that adverse outcomes were more likely to occur following vaccination
      versus accidental infection. CONCLUSIONS: The results of this study suggest that
      the main barrier to vaccination may be fear associated with possible vaccine
      adverse effects and a willingness to risk accidental infection rather than be
      vaccinated. More information and training about the potential benefits of
      vaccination, as well as the potential adverse outcomes associated with accidental
      infection, is therefore warranted.

PMID- 19864446
TI  - In utero and lactational exposure to bisphenol A, in contrast to ethinyl
      estradiol, does not alter sexually dimorphic behavior, puberty, fertility, and
      anatomy of female LE rats.
AB  - Many chemicals released into the environment display estrogenic activity
      including the oral contraceptive ethinyl estradiol (EE2) and the plastic monomer
      bisphenol A (BPA). EE2 is present in some aquatic systems at concentrations
      sufficient to alter reproductive function of fishes. Many concerns have been
      raised about the potential effects of BPA. The National Toxicology Program rated
      the potential effects of low doses of BPA on behavior and central nervous system
      (CNS) as an area of "some concern," whereas most effects were rated as of
      "negligible" or "minimal" concern. However, the number of robust studies in this
      area was limited. The current study was designed to determine if maternal
      exposure to relatively low oral doses of EE2 or BPA in utero and during lactation
      would alter the expression of well-characterized sexually dimorphic behaviors or
      alter the age of puberty or reproductive function in the female Long-Evans rat
      offspring. Pregnant rats were gavaged with vehicle, EE2 (0.05-50 microg/kg/day),
      or BPA (2, 20, and 200 microg/kg/day) from day 7 of gestation to postnatal day
      (PND) 18, and the female offspring were studied. EE2 (50 microg/kg/day) increased
      anogenital distance and reduced pup body weight at PND2, accelerated the age at
      vaginal opening, reduced F1 fertility and F2 litter sizes, and induced
      malformations of the external genitalia (5 microg/kg). F1 females exposed to EE2
      also displayed a reduced (male-like) saccharin preference (5 microg/kg) and
      absence of lordosis behavior (15 microg/kg), indications of defeminization of the
      CNS. BPA had no effect on any of the aforementioned measures. These results
      demonstrate that developmental exposure to pharmacologically relevant dosage
      levels of EE2 can permanently disrupt the reproductive morphology and function of
      the female rat.

PMID- 19864447
TI  - Hypertrophic remodeling of subcutaneous small resistance arteries in patients
      with Cushing's syndrome.
AB  - OBJECTIVE: Structural alterations of small resistance arteries in essential
      hypertensive patients (EH) are mostly characterized by inward eutrophic
      remodeling. However, we observed hypertrophic remodeling in patients with
      renovascular hypertension, in those with acromegaly, as well as in patients with
      non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral
      growth factors on vascular structure, even independent from the hemodynamic load.
      Cortisol may stimulate the renin-angiotensin system and may induce cardiac
      hypertrophy. However, presently no data are available about small artery
      structure in patients with Cushing's syndrome. SUBJECTS: We have investigated the
      structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12
      EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries
      from sc fat were dissected and mounted on a micromyograph. The normalized
      internal diameter, media thickness, media to lumen ratio, and the media cross
      sectional area were measured, as well as indices of oxidative stress. RESULTS:
      Demographic variables were similar in the three groups, except for clinic blood
      pressure. The media to lumen ratio was significantly greater in EH and CS,
      compared with NT; no difference was observed between EH and CS. The media cross
      sectional area was significantly greater in CS compared with EH and with NT. An
      increased vascular oxidative stress was present in CS, as demonstrated by
      increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric
      oxide synthase in the microvessels. CONCLUSION: Our results suggest the presence
      of hypertrophic remodeling in sc small resistance arteries of CS, probably as a
      consequence of growth-promoting properties of circulating cortisol and/or
      increased vascular oxidative stress.

PMID- 19864448
TI  - Attenuated sex steroid receptor expression in fallopian tube of women with
      ectopic pregnancy.
AB  - CONTEXT: Sex steroid hormone receptor (SHR) dynamics are well-documented in human
      endometrium but have not been comprehensively studied in Fallopian tube (FT).
      OBJECTIVE: The aim of the study was to compare expression patterns and hormonal
      regulation of SHR in FT with that described in endometrium and to determine
      whether SHR expression is altered in FT of women with ectopic pregnancy (EP).
      DESIGN: Tissue was analyzed and cultured. PATIENTS OR OTHER PARTICIPANTS: Women
      undergoing surgery for benign gynecological conditions (n = 14) and EP (n = 6)
      participated in the study. INTERVENTIONS: Quantitative RT-PCR and
      immunohistochemistry were used to determine SHR mRNA expression and protein
      localization, respectively. SHR levels were measured in tubal explant cultures
      stimulated with estrogen and progestogen. RESULTS: ERalpha and ERbeta mRNAs were
      constitutively expressed in FT during the menstrual cycle. PR-AB and PR-B mRNAs
      were decreased in midluteal phase compared to follicular phase. ERalpha, PR-AB,
      and PR-B mRNAs were down-regulated in human FT in vitro by treatment with
      progestogen. ERalpha, ERbeta1, ERbeta2, PR, and AR proteins localized to cell
      nuclei of epithelium, stroma, and smooth muscle of nonpregnant FT. In FT from
      women with EP, PR-B mRNA was decreased when compared to midluteal FT, and ERalpha
      protein was not detected. CONCLUSIONS: SHR expression in FT is different from
      that observed in endometrium recovered at similar stages of the menstrual cycle,
      and expression in FT from women with EP is also altered compared with normal FT.
      These data are an important benchmark for furthering the understanding of normal
      human FT physiology, changes in expression of SHR in FT in response to
      progesterone, and disorders of FT function, such as EP.

PMID- 19864449
TI  - Effect of short-term free Fatty acids elevation on mitochondrial function in
      skeletal muscle of healthy individuals.
AB  - CONTEXT: Mitochondrial dysfunction has been proposed as an underlying mechanism
      in the pathogenesis of insulin resistance and type 2 diabetes mellitus.
      OBJECTIVE: To determine whether mitochondrial dysfunction plays a role in the
      free fatty acid (FFA)-induced impairment in insulin action in skeletal muscle of
      healthy subjects. DESIGN: Eleven lean normal glucose tolerant individuals
      received 8 h lipid and saline infusion on separate days with a euglycemic insulin
      clamp during the last 2 h. Vastus lateralis muscle biopsies were performed at
      baseline and after 6 h lipid or saline infusion. Inner mitochondrial membrane
      potential (Psi(m)) and mitochondrial mass were determined ex vivo by confocal
      microscopy. RESULTS: Compared with saline infusion, lipid infusion reduced whole
      body glucose uptake by 22% (P < 0.05). Psi(m) decreased by 33% (P < 0.005) after
      lipid infusion and the decrement in Psi(m) correlated with change in plasma FFA
      after lipid infusion (r = 0.753; P < 0.005). Mitochondrial content and morphology
      did not change after lipid infusion. No significant changes in genes expression,
      citrate synthase activity, and total ATP content were observed after either lipid
      or saline infusion. CONCLUSIONS: Short-term physiological increase in plasma FFA
      concentration in lean normal glucose tolerant subjects induces insulin resistance
      and impairs mitochondrial membrane potential but has no significant effects on
      mitochondrial content, gene expression, ATP content, or citrate synthase
      activity.

PMID- 19864450
TI  - Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine
      PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and
      paraganglioma.
AB  - CONTEXT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission
      tomography (PET) agents are available for the localization of paraganglioma
      (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D
      glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA). OBJECTIVE: The
      objective of the study was to establish the optimal approach to the functional
      imaging of PGL and examine the link between genotype-specific tumor biology and
      imaging. DESIGN: This was a prospective observational study. INTERVENTION: There
      were no interventions. PATIENTS: Fifty-two patients (28 males, 24 females, aged
      46.8 +/- 14.2 yr): 20 with nonmetastatic PGL (11 adrenal), 28 with metastatic PGL
      (13 adrenal), and four in whom PGL was ruled out; 22 PGLs were of the succinate
      dehydrogenase subunit B (SDHB) genotype. MAIN OUTCOME MEASURES: Sensitivity of
      (18)F-DOPA, (18)F-FDG, and (18)F-FDA PET, (123)I-MIBG scintigraphy, computed
      tomography (CT), and magnetic resonance imaging (MRI) for the localization of PGL
      were measured. RESULTS: Sensitivities for localizing nonmetastatic PGL were 100%
      for CT and/or MRI, 81% for (18)F-DOPA PET, 88% for (18)F-FDG PET/CT, 78% for
      (18)F-FDA PET/CT, and 78% for (123)I-MIBG scintigraphy. For metastatic PGL,
      sensitivity in reference to CT/MRI was 45% for (18)F-DOPA PET, 74% for (18)F-FDG
      PET/CT, 76% for (18)F-FDA PET/CT, and 57% for (123)I-MIBG scintigraphy. In
      patients with SDHB metastatic PGL, (18)F-FDA and (18)F-FDG have a higher
      sensitivity (82 and 83%) than (123)I-MIBG (57%) and (18)F-DOPA (20%).
      CONCLUSIONS: (18)F-FDA PET/CT is the preferred technique for the localization of
      the primary PGL and to rule out metastases. Second best, equal alternatives are
      (18)F-DOPA PET and (123)I-MIBG scintigraphy. For patients with known metastatic
      PGL, we recommend (18)F-FDA PET in patients with an unknown genotype, (18)F-FDG
      or (18)F-FDA PET in SDHB mutation carriers, and (18)F-DOPA or (18)F-FDA PET in
      non-SDHB patients.

PMID- 19864451
TI  - The exon-3 deleted growth hormone receptor polymorphism predisposes to long-term
      complications of acromegaly.
AB  - OBJECTIVE: The aim of the study was to evaluate the impact of the genomic
      deletion of exon 3 of the GH receptor (d3GHR) on long-term clinical outcome of
      acromegaly in a well-characterized cohort of patients with long-term remission of
      acromegaly. DESIGN: We conducted a cross-sectional study. METHODS: The presence
      of the d3GHR polymorphism was assessed in 86 acromegalic patients with long-term
      disease control and related to anthropometric parameters, cardiovascular risk
      factors, osteoarthritis, bone mineral density, colonic polyps and diverticulae,
      and dolichocolon. RESULTS: Fifty-one patients had two wild-type alleles (59%),
      whereas 29 patients (34%) had one allele and six patients (7%) had two alleles
      encoding for the d3GHR isoform. Carriers of the d3GHR isoform showed increased
      prevalence of osteoarthritis, especially of the hip [adjusted odds ratio (OR),
      5.2; 95% confidence interval (CI), 3.2-7.1], of adenomatous polyps (adjusted OR,
      4.1; 95% CI, 2.4-5.6), and dolichocolon (adjusted OR, 3.2; 95% CI, 1.8-4.6).
      Anthropometric parameters, cardiovascular risk factors, bone mineral density, and
      (non)vertebral fractures were not significantly different between patients with
      and without the d3GHR allele. CONCLUSION: In patients with long-term cured
      acromegaly, the d3GHR polymorphism is associated with an increased prevalence of
      irreversible comorbidities such as osteoarthritis, dolichocolon, and adenomatous
      colonic polyps, but not with other comorbidities such as cardiovascular risk
      factors.

PMID- 19864452
TI  - Saxagliptin added to a thiazolidinedione improves glycemic control in patients
      with type 2 diabetes and inadequate control on thiazolidinedione alone.
AB  - CONTEXT: Due to the natural progression of type 2 diabetes (T2D), most patients
      require combination therapy to maintain glycemic control. OBJECTIVE: Our
      objective was to evaluate efficacy and safety of saxagliptin plus
      thiazolidinedione (TZD) in patients with T2D and inadequate glycemic control on
      TZD monotherapy. DESIGN: The study was a multicenter, randomized, double-blind,
      placebo (PBO)-controlled phase 3 trial conducted from March 13, 2006, to October
      15, 2007. SETTING: Patients were recruited from 172 outpatient centers. PATIENTS:
      Patients with inadequately controlled T2D [glycosylated hemoglobin (HbA(1c)) 7.0
      10.5%], 18-77 yr, receiving stable TZD monotherapy (pioglitazone 30 or 45 mg or
      rosiglitazone 4 or 8 mg) for at least 12 wk before screening were eligible.
      INTERVENTIONS: A total of 565 patients were randomized and treated with
      saxagliptin (2.5 or 5 mg) or PBO, once daily, plus stable TZD dose for 24 wk.
      MAIN OUTCOME MEASURES: Primary outcome was change in HbA(1c) from baseline to wk
      24. Secondary outcomes were change from baseline to wk 24 in fasting plasma
      glucose, proportion of patients achieving HbA(1c) less than 7.0%, and
      postprandial glucose area under the curve. RESULTS: At 24 wk, saxagliptin (2.5
      and 5 mg) plus TZD demonstrated statistically significant adjusted mean decreases
      vs. PBO in HbA(1c) [-0.66% (P = 0.0007) and -0.94% (P < 0.0001) vs. -0.30%] and
      fasting plasma glucose [-0.8 mmol/liter (P = 0.0053) and -1 mmol/liter (P =
      0.0005) vs. -0.2 mmol/liter]. Proportion of patients achieving HbA(1c) less than
      7.0% was greater for saxagliptin (2.5 and 5 mg) plus TZD vs. PBO [42.2% (P =
      0.001) and 41.8% (P = 0.0013) vs. 25.6%]. Postprandial glucose area under the
      curve was significantly reduced [-436 mmol x min/liter (saxagliptin 2.5 mg plus
      TZD) and -514 mmol x min/liter (saxagliptin 5 mg plus TZD) vs. -149 mmol x
      min/liter (PBO)]. Saxagliptin was generally well tolerated; adverse event
      occurrence and reported hypoglycemic events were similar across all groups.
      CONCLUSIONS: Saxagliptin added to TZD provided statistically significant
      improvements in key parameters of glycemic control vs. TZD monotherapy and was
      generally well tolerated.

PMID- 19864454
TI  - Two short children born small for gestational age with insulin-like growth factor
      1 receptor haploinsufficiency illustrate the heterogeneity of its phenotype.
AB  - CONTEXT: Small for gestational age (SGA)-born children comprise a heterogeneous
      group in which only few genetic causes have been identified. OBJECTIVE: To
      determine copy number variations in 18 growth-related genes in 100 SGA children
      with persistent short stature. METHODS: Copy number variations in 18 growth
      related genes (SHOX, GH1, GHR, IGF1, IGF1R, IGF2, IGFBP1-6, NSD1, GRB10, STAT5B,
      ALS, SOCS2, and SOCS3) were determined by an "in house" multiplex ligation
      dependent probe amplification kit. The deletions were further characterized by
      single-nucleotide polymorphism array analysis. RESULTS: Two heterozygous de novo
      insulin-like growth factor 1 receptor (IGF1R) deletions were found: a deletion of
      the complete IGF1R gene (15q26.3, exons 1-21), including distally flanking
      sequences, and a deletion comprising exons 3-21, extending further into the
      telomeric region. In one case, serum IGF-I was low (-2.78 sd score), probably
      because of a coexisting growth hormone (GH) deficiency. Both children increased
      their height during GH treatment (1 mg/m(2) per day). Functional studies in skin
      fibroblast cultures demonstrated similar levels of IGF1R autophosphorylation and
      a reduced activation of protein kinase B/Akt upon a challenge with IGF-I in
      comparison with controls. CONCLUSIONS: IGF1R haploinsufficiency was present in 2
      of 100 short SGA children. GH therapy resulted in moderate catch-up growth in our
      patients. A review of the literature shows that small birth size, short stature,
      small head size, relatively high IGF-I levels, developmental delay, and
      micrognathia are the main predictors for an IGF1R deletion.

PMID- 19864453
TI  - Correlation of telomere length and telomerase activity with occult ovarian
      insufficiency.
AB  - BACKGROUND: Occult ovarian insufficiency is associated with infertility, impaired
      response to ovarian stimulation, and reduced live birth rates in women treated
      with assisted reproductive technologies. Although a decline in ovarian follicle
      number is expected with age, the proximate causes of occult ovarian insufficiency
      in young women remain poorly understood. Abnormalities in telomere length and
      telomerase activity in human granulosa cells may serve as molecular markers for
      this condition. METHODS: A cross-sectional study was performed. Subjects (37 yr
      old or less) undergoing in vitro fertilization were classified as cases of occult
      ovarian insufficiency or controls with mechanical infertility (male or tubal
      factor). Granulosa cells were acquired at the time of oocyte retrieval to
      quantify telomere length and telomerase activity. RESULTS: Fifty-four women were
      enrolled. Human granulosa cell telomerase activity was demonstrated, and lack of
      granulosa cell telomerase activity was associated with occult ovarian
      insufficiency (odds ratio, 11.0; 95% confidence interval, 1.3-495.6; P = 0.02).
      Telomeres were shorter in women with occult ovarian insufficiency than in
      controls (relative telomere/single copy gene ratio, 1.88 vs. 3.15; P = 0.039).
      CONCLUSIONS: Aberrant telomere homeostasis is associated with occult ovarian
      insufficiency in young women. This finding is consistent with the presence of
      telomeric attenuation that has been shown in multiple age-related conditions.

PMID- 19864455
TI  - Receptor type protein tyrosine phosphatase-kappa mediates cross-talk between
      transforming growth factor-beta and epidermal growth factor receptor signaling
      pathways in human keratinocytes.
AB  - Epidermal growth factor receptor (EGFR) signaling pathways promote human
      keratinocyte survival and proliferation. In contrast, transforming growth factor
      beta (TGF-beta) signaling pathways are strongly anti-proliferative. Receptor type
      protein tyrosine phosphatase-kappa (RPTP-kappa) specifically dephosphorylates
      EGFR, thereby blocking EGFR-dependent signaling, and inhibiting proliferation. We
      report here that RPTP-kappa mediates functional integration of EGFR and TGF-beta
      signaling pathways in human keratinocytes. TGF-beta up-regulates RPTP-kappa mRNA
      and protein, in a dose and time dependent manner. Induction of RPTP-kappa by TGF
      beta significantly decreases basal and EGF-stimulated EGFR tyrosine
      phosphorylation. shRNA-mediated reduction of TGF-beta-induced RPTP-kappa
      significantly attenuates the ability of TGF-beta to inhibit proliferation. RPTP
      kappa induction is dependent on activation of transcription factors Smad3 and
      Smad4. Inhibition of TGF-beta receptor kinase completely prevents induction of
      RPTP-kappa. Chromatin immunoprecipitation assays reveal that TGF-beta stimulates
      Smad3 and Smad4 binding to RPTP-kappa gene promoter. Smad3/4 binding is localized
      to an 186-base pair region, which contains a consensus Smad3-binding element.
      These data describe a novel mechanism of cross-talk between EGFR and TGF-beta
      pathways, in which RPTP-kappa functions to integrate growth-promoting and growth
      inhibiting signaling pathways.

PMID- 19864457
TI  - The E3 ubiquitin ligases Hrd1 and gp78 bind to and promote cholera toxin retro
      translocation.
AB  - To cause disease, cholera toxin (CT) is transported from the cell surface to the
      endoplasmic reticulum (ER) lumen where the catalytic CTA1 subunit retro
      translocates to the cytosol to induce pathological water secretion. Two retro
      translocon components are the Derlins and ER-associated multi-spanning E3
      ubiquitin ligases including Hrd1 and gp78. We demonstrated previously that Derlin
      1 facilitates CTA1 retro-translocation. However, as CTA1 is neither ubiquitinated
      on lysines nor at its N-terminus, the role of E3 ligases in toxin retro
      translocation is unclear. Here, we show that expression of mutant Hrd1 and gp78
      and a mutant E2-conjugating enzyme dedicated to retro-translocation (Ube2g2)
      decrease CTA1 retro-translocation. Hrd1 knockdown also attenuated toxin retro
      translocation. Binding studies demonstrate that Hrd1 and gp78 interact with CT
      and protein disulfide isomerase, an ER chaperone that unfolds CTA1 to initiate
      translocation. Moreover, we find that the toxin's association with Hrd1 and gp78
      is blocked by dominant-negative Derlin-1, suggesting that CT is targeted
      initially to Derlin-1 and then transferred to Hrd1 and gp78. These data
      demonstrate a role of the E3 ubiquitin ligases in CTA1 retro-translocation,
      implicate a sequence of events experienced by the toxin on the ER membrane, and
      raise the possibility that ubiquitination is involved in the transport process.

PMID- 19864456
TI  - Role of Rap1B and tumor suppressor PTEN in the negative regulation of
      lysophosphatidic acid--induced migration by isoproterenol in glioma cells.
AB  - The clarification of mechanisms that negatively regulate the invasive behavior of
      human glioma cells is of great importance in order to find new methods of
      treatment. In this study, we have focused on the negative regulation of
      lysophosphatidic acid (LPA)-induced migration in glioma cells. Using small
      interference RNA and dominant-negative gene strategies in addition to
      pharmacological tools, we found that isoproterenol (ISO) and sphingosine-1
      phosphate (S1P) negatively but differently regulate the LPA-induced migration.
      ISO-induced suppression of the migration of glioma cells occurs via beta(2)
      adrenergic receptor/cAMP/Epac/Rap1B/inhibition of Rac, whereas S1P has been shown
      to suppress the migration of the cells through S1P(2) receptor/Rho-mediated down
      regulation of Rac1. The expression of tumor suppressor phosphatase and tensin
      homolog deleted on chromosome 10 (PTEN) is required for the inhibitory ISO
      induced and Rap1B-mediated actions on the migration, Rac1 activation, and Akt
      activation in response to LPA. Thus, the PTEN-mediated down-regulation of
      phosphatidylinositol 3-kinase activity may be involved in the regulation of Rap1B
      dependent inhibition of Rac1 activity. These findings suggest that there are at
      least two distinct inhibitory pathways, which are mediated by the S1P(2) receptor
      and beta(2)-adrenergic receptor, to control the migratory, hence invasive,
      behavior of glioma cells.

PMID- 19864458
TI  - MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor
      recycling.
AB  - Endocytic recycling of receptors and lipids occurs via a complex network of
      tubular and vesicular membranes. EHD1 is a key regulator of endocytosis and
      associates with tubular membranes to facilitate recycling. Although EHD proteins
      tubulate membranes in vitro, EHD1 primarily associates with preexisting tubules
      in vivo. How EHD1 is recruited to these tubular endosomes remains unclear. We
      have determined that the Rab8-interacting protein, MICAL-L1, associates with
      EHD1, with both proteins colocalizing to long tubular membranes, in vitro and in
      live cells. MICAL-L1 is a largely uncharacterized member of the MICAL-family of
      proteins that uniquely contains two asparagine-proline-phenylalanine motifs,
      sequences that typically interact with EH-domains. Our data show that the MICAL
      L1 C-terminal coiled-coil region is necessary and sufficient for its localization
      to tubular membranes. Moreover, we provide unexpected evidence that endogenous
      MICAL-L1 can link both EHD1 and Rab8a to these structures, as its depletion leads
      to loss of the EHD1-Rab8a interaction and the absence of both of these proteins
      from the membrane tubules. Finally, we demonstrate that MICAL-L1 is essential for
      efficient endocytic recycling. These data implicate MICAL-L1 as an unusual type
      of Rab effector that regulates endocytic recycling by recruiting and linking EHD1
      and Rab8a on membrane tubules.

PMID- 19864459
TI  - Roles of formin nodes and myosin motor activity in Mid1p-dependent contractile
      ring assembly during fission yeast cytokinesis.
AB  - Two prevailing models have emerged to explain the mechanism of contractile-ring
      assembly during cytokinesis in the fission yeast Schizosaccharomyces pombe: the
      spot/leading cable model and the search, capture, pull, and release (SCPR) model.
      We tested some of the basic assumptions of the two models. Monte Carlo
      simulations of the SCPR model require that the formin Cdc12p is present in >30
      nodes from which actin filaments are nucleated and captured by myosin-II in
      neighboring nodes. The force produced by myosin motors pulls the nodes together
      to form a compact contractile ring. Live microscopy of cells expressing Cdc12p
      fluorescent fusion proteins shows for the first time that Cdc12p localizes to a
      broad band of 30-50 dynamic nodes, where actin filaments are nucleated in random
      directions. The proposed progenitor spot, essential for the spot/leading cable
      model, usually disappears without nucleating actin filaments. alpha-Actinin ain1
      deletion cells form a normal contractile ring through nodes in the absence of the
      spot. Myosin motor activity is required to condense the nodes into a contractile
      ring, based on slower or absent node condensation in myo2-E1 and UCS rng3-65
      mutants. Taken together, these data provide strong support for the SCPR model of
      contractile-ring formation in cytokinesis.

PMID- 19864460
TI  - Mammalian pre-mRNA 3' end processing factor CF I m 68 functions in mRNA export.
AB  - Export of mRNA from the nucleus is linked to proper processing and packaging into
      ribonucleoprotein complexes. Although several observations indicate a coupling
      between mRNA 3' end formation and export, it is not known how these two processes
      are mechanistically connected. Here, we show that a subunit of the mammalian pre
      mRNA 3' end processing complex, CF I(m)68, stimulates mRNA export. CF I(m)68
      shuttles between the nucleus and the cytoplasm in a transcription-dependent
      manner and interacts with the mRNA export receptor NXF1/TAP. Consistent with the
      idea that CF I(m)68 may act as a novel adaptor for NXF1/TAP, we show that CF
      I(m)68 promotes the export of a reporter mRNA as well as of endogenous mRNAs,
      whereas silencing by RNAi results in the accumulation of mRNAs in the nucleus.
      Moreover, CF I(m)68 associates with 80S ribosomes but not polysomes, suggesting
      that it is part of the mRNP that is remodeled in the cytoplasm during the initial
      stages of translation. These results reveal a novel function for the pre-mRNA 3'
      end processing factor CF I(m)68 in mRNA export.

PMID- 19864461
TI  - Drosophila lysophospholipid acyltransferases are specifically required for germ
      cell development.
AB  - Enzymes of the membrane-bound O-acyltransferase (MBOAT) family add fatty acyl
      chains to a diverse range of protein and lipid substrates. A chromosomal
      translocation disrupting human MBOAT1 results in a novel syndrome characterized
      by male sterility and brachydactyly. We have found that the Drosophila homologues
      of MBOAT1, Oysgedart (Oys), Nessy (Nes), and Farjavit (Frj), are lysophospholipid
      acyltransferases. When expressed in yeast, these MBOATs esterify specific
      lysophospholipids preferentially with unsaturated fatty acids. Generating null
      mutations for each gene allowed us to identify redundant functions for Oys and
      Nes in two distinct aspects of Drosophila germ cell development. Embryos lacking
      both oys and nes show defects in the ability of germ cells to migrate into the
      mesoderm, a process guided by lipid signals. In addition, oys nes double mutant
      adult males are sterile due to specific defects in spermatid individualization.
      oys nes mutant testes, as well as single, double, and triple mutant whole adult
      animals, show an increase in the saturated fatty acid content of several
      phospholipid species. Our findings suggest that lysophospholipid acyltransferase
      activity is essential for germline development and could provide a mechanistic
      explanation for the etiology of the human MBOAT1 mutation.

PMID- 19864462
TI  - The Nup107-160 nucleoporin complex promotes mitotic events via control of the
      localization state of the chromosome passenger complex.
AB  - The human Nup107-160 nucleoporin complex plays a major role in formation of the
      nuclear pore complex and is localized to kinetochores in mitosis. Here we report
      that Seh1, a component of the Nup107-160 complex, functions in chromosome
      alignment and segregation by regulating the centromeric localization of Aurora B
      and other chromosome passenger complex proteins. Localization of CENP-E is not
      affected by Seh1 depletion and analysis by electron microscopy showed that
      microtubule kinetochore attachments are intact. Seh1-depleted cells show impaired
      Aurora B localization, which results in severe defects in biorientation and
      organization of the spindle midzone and midbody. Our results indicate that a
      major function of the Nup107 complex in mitosis is to ensure the proper
      localization of the CPC at the centromere.

PMID- 19864463
TI  - Retrograde neurotrophic signaling requires a protein interacting with receptor
      tyrosine kinases via C2H2 zinc fingers.
AB  - Neurotrophins at axonal terminals signal to cell bodies to regulate neuronal
      development via signaling endosomes containing activated Trk receptor tyrosine
      kinases and mitogen-activated protein kinases (MAPKs). Requirements for the
      formation of signaling endosomes remain, however, poorly characterized. Here we
      show that a novel Trk-interacting protein, NTRAP (neurotrophic factor receptor
      associated protein), plays a crucial role in this signaling process. NTRAP
      interacts with the Trk intracellular domain through its C(2)H(2) zinc fingers in
      a kinase-dependent manner. It is associated with vesicles, some of which contain
      markers for signaling endosomes. Inhibition of NTRAP function suppresses
      neurotrophin-induced neurite outgrowth in PC12 cells by altering TrkA endocytic
      traffic, inhibiting the formation of endosomes containing persistently active
      MAPKs. In compartmentalized sensory neuron cultures, down-regulation of NTRAP
      abolishes the ability of neurotrophins applied to distal axons to activate the
      transcription factor adenosine 3',5'-monophosphate response element-binding
      protein (CREB) and to promote neuronal survival. We propose that NTRAP regulates
      retrograde neurotrophic signaling by controlling the formation of signaling
      endosomes.

PMID- 19864466
TI  - The consequences of early discharge after hip arthroplasty for patient outcomes
      and health care costs: comparison of three centres with differing durations of
      stay.
AB  - OBJECTIVE: To compare outcomes from hip arthroplasty between a surgical unit with
      a rapid discharge policy and two comparison units to test the hypothesis that the
      centre with rapid discharge has outcomes that are not inferior to the comparison
      sites. DESIGN: Prospective cohort study. SUBJECTS: Consecutive consenting
      patients receiving primary hip arthroplasty during 12 months beginning July 2006
      in three UK National Health Service surgical units. One has shortened
      postoperative stay to median three days; one was a new treatment centre with
      median stay of five days; the third was a traditional unit with median stay of
      six days (N = 316, 119, 87, respectively). METHODS: Patients were assessed
      preoperatively and six weeks postoperatively. The primary indicator of function
      was the Oxford Hip Score. Additional secondary measures included further self
      report indicators of function and quality of life and health service costs.
      RESULTS: Patient outcome in the unit with rapid discharge was not impaired by
      comparison with the other sites on any measure: Oxford Hip Score decreased from
      49 to 27 in the short-stay unit, from 40 to 30 in the treatment centre and from
      43 to 32 in the traditional unit. Cost of arthroplasty was least in the short
      stay unit, although there was potential for cost savings in each. CONCLUSION:
      Short postoperative stay after hip arthroplasty can be achieved without intensive
      patient preparation or post-discharge care and without compromising short-term
      patient outcome or increasing health care costs. Longer term follow-up is needed.

PMID- 19864464
TI  - Phosphatidylinositol 3,4,5-trisphosphate localization in recycling endosomes is
      necessary for AP-1B-dependent sorting in polarized epithelial cells.
AB  - Polarized epithelial cells coexpress two almost identical AP-1 clathrin adaptor
      complexes: the ubiquitously expressed AP-1A and the epithelial cell-specific AP
      1B. The only difference between the two complexes is the incorporation of the
      respective medium subunits micro1A or micro1B, which are responsible for the
      different functions of AP-1A and AP-1B in TGN to endosome or endosome to
      basolateral membrane targeting, respectively. Here we demonstrate that the C
      terminus of micro1B is important for AP-1B recruitment onto recycling endosomes.
      We define a patch of three amino acid residues in micro1B that are necessary for
      recruitment of AP-1B onto recycling endosomes containing phosphatidylinositol
      3,4,5-trisphosphate [PI(3,4,5)P(3)]. We found this lipid enriched in recycling
      endosomes of epithelial cells only when AP-1B is expressed. Interfering with
      PI(3,4,5)P(3) formation leads to displacement of AP-1B from recycling endosomes
      and missorting of AP-1B-dependent cargo to the apical plasma membrane. In
      conclusion, PI(3,4,5)P(3) formation in recycling endosomes is essential for AP-1B
      function.

PMID- 19864467
TI  - Does CO(2) flushing of the empty CPB circuit decrease the number of gaseous
      emboli in the prime?
AB  - Twenty (20) CPB-circuits were randomized to a CO(2) group or a control group. In
      the CO( 2) group, each circuit was flushed with CO(2) (10L/min) at the top of the
      venous reservoir for 5 minutes, after which priming fluid was added without
      interruption of the CO(2) inflow. Control group circuits were not flushed and
      contained air. A perfusionist, blinded to the study, started the pump (5L/min),
      ventilated the oxygenator (3L O(2)/min), and knocked on the oxygenator 20 times
      during the first and 14(th) minutes. Arterial line microemboli counts were
      registered with a Doppler for 15 minutes. In both groups, the median number of
      microemboli was highest during the first minute, 380.5 (288.75/422.25,
      25(th)/75(th) percentile) counts in the control group versus 264.5
      (171.75/422.25) counts in the CO( 2) group (p=0.01). Throughout the experiment,
      the median microembolic count minute by minute in the CO(2) group remained lower
      (p < or = 0 .004) than in the control group. Knocking on the reservoir (14(th)
      minute) increased the microemboli counts in both groups (p<0.01). The median
      values during the 15(th) minute were 15.5 and 0.5 in the control and the CO(2)
      groups, respectively, which were 9% (15.5/173) and 0.5% (0.5/87), respectively,
      of the values registered after 14 minutes. In conclusion, CO( 2) flushing of the
      empty circuit decreases the number of gaseous emboli in the prime compared with a
      conventional circuit that contains air before being primed with fluid. Knocking
      of the oxygenator releases gaseous emboli and the duration of re-circulating the
      circuit with prime influences the number of microemboli.

PMID- 19864465
TI  - A novel mouse HSF3 has the potential to activate nonclassical heat-shock genes
      during heat shock.
AB  - The heat-shock response is characterized by the expression of a set of classical
      heat-shock genes, and is regulated by heat-shock transcription factor 1 (HSF1) in
      mammals. However, comprehensive analyses of gene expression have revealed very
      large numbers of inducible genes in cells exposed to heat shock. It is believed
      that HSF1 is required for the heat-inducible expression of these genes although
      HSF2 and HSF4 modulate some of the gene expression. Here, we identified a novel
      mouse HSF3 (mHSF3) translocated into the nucleus during heat shock. However,
      mHSF3 did not activate classical heat-shock genes such as Hsp70. Remarkably,
      overexpression of mHSF3 restored the expression of nonclassical heat-shock genes
      such as PDZK3 and PROM2 in HSF1-null mouse embryonic fibroblasts (MEFs). Although
      down-regulation of mHSF3 expression had no effect on gene expression or cell
      survival in wild-type MEF cells, it abolished the moderate expression of PDZK3
      mRNA and reduced cell survival in HSF1-null MEF cells during heat shock. We
      propose that mHSF3 represents a unique HSF that has the potential to activate
      only nonclassical heat-shock genes to protect cells from detrimental stresses.

PMID- 19864468
TI  - Phylodynamics of HIV-1 from a phase-III AIDS vaccine trial in North America.
AB  - In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1
      vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1
      infection from North America and the Netherlands. A total of 368 individuals
      became infected with HIV-1 during the trial. The envelope glycoprotein gene
      (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced
      from clinical samples taken as close as possible to the time of diagnosis,
      rendering a final data set of 1,047 sequences (1,032 from North America and 15
      from the Netherlands). Here, we used these data in combination with other
      sequences available in public databases to assess HIV-1 variation as a function
      of vaccination treatment, geographic region, race, risk behavior, and viral load.
      Viral samples did not show any phylogenetic structure for any of these factors,
      but individuals with different viral loads showed significant differences (P =
      0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B
      was 1966-1970. Despite the fact that the number of AIDS cases has decreased in
      North America since the early 90s, HIV-1 genetic diversity seems to have remained
      almost constant over time. This study represents one of the largest molecular
      epidemiologic surveys of viruses responsible for new HIV-1 infections in North
      America and could help the selection of epidemiologically representative vaccine
      antigens to include in the next generation of candidate HIV-1 vaccines.

PMID- 19864469
TI  - Large-scale parsimony analysis of metazoan indels in protein-coding genes.
AB  - Insertions and deletions (indels) are considered to be rare evolutionary events,
      the analysis of which may resolve controversial phylogenetic relationships.
      Indeed, indel characters are often assumed to be less homoplastic than amino acid
      and nucleotide substitutions and, consequently, more reliable markers for
      phylogenetic reconstruction. In this study, we analyzed indels from over 1,000
      metazoan orthologous genes. We studied the impact of different species sampling,
      ortholog data sets, lengths of included indels, and indel-coding methods on the
      resulting metazoan tree. Our results show that, similar to sequence
      substitutions, indels are homoplastic characters, and their analysis is sensitive
      to the long-branch attraction artifact. Furthermore, improving the taxon sampling
      and choosing a closely related outgroup greatly impact the phylogenetic
      inference. Our indel-based inferences support the Ecdysozoa hypothesis over the
      Coelomata hypothesis and suggest that sponges are a sister clade to other
      animals.

PMID- 19864470
TI  - Evolutionary fingerprinting of genes.
AB  - Over time, natural selection molds every gene into a unique mosaic of sites
      evolving rapidly or resisting change-an "evolutionary fingerprint" of the gene.
      Aspects of this evolutionary fingerprint, such as the site-specific ratio of
      nonsynonymous to synonymous substitution rates (dN/dS), are commonly used to
      identify genetic features of potential biological interest; however, no framework
      exists for comparing evolutionary fingerprints between genes. We hypothesize that
      protein-coding genes with similar protein structure and/or function tend to have
      similar evolutionary fingerprints and that comparing evolutionary fingerprints
      can be useful for discovering similarities between genes in a way that is
      analogous to, but independent of, discovery of similarity via sequence-based
      comparison tools such as Blast. To test this hypothesis, we develop a novel model
      of coding sequence evolution that uses a general bivariate discrete
      parameterization of the evolutionary rates. We show that this approach provides a
      better fit to the data using a smaller number of parameters than existing models.
      Next, we use the model to represent evolutionary fingerprints as probability
      distributions and present a methodology for comparing these distributions in a
      way that is robust against variations in data set size and divergence. Finally,
      using sequences of three rapidly evolving RNA viruses (HIV-1, hepatitis C virus,
      and influenza A virus), we demonstrate that genes within the same functional
      group tend to have similar evolutionary fingerprints. Our framework provides a
      sound statistical foundation for efficient inference and comparison of
      evolutionary rate patterns in arbitrary collections of gene alignments,
      clustering homologous and nonhomologous genes, and investigation of biological
      and functional correlates of evolutionary rates.

PMID- 19864471
TI  - Differential effects of reactive nitrogen species on DNA base excision repair
      initiated by the alkyladenine DNA glycosylase.
AB  - Chronic generation of reactive nitrogen species (RNS) can cause DNA damage and
      may also directly modify DNA repair proteins. RNS-modified DNA is repaired
      predominantly by the base excision repair (BER) pathway, which includes the
      alkyladenine DNA glycosylase (AAG). The AAG active site contains several
      tyrosines and cysteines that are potential sites for modification by RNS. In
      vitro, we demonstrate that RNS differentially alter AAG activity depending on the
      site and type of modification. Nitration of tyrosine 162 impaired 1,N(6)
      ethenoadenine (epsilonA)-excision activity, whereas nitrosation of cysteine 167
      increased epsilonA excision. To understand the effects of RNS on BER in vivo, we
      examined intestinal adenomas for levels of inducible nitric oxide synthase (iNOS)
      and AAG. A striking correlation between AAG and iNOS expression was observed (r =
      0.76, P = 0.00002). Interestingly, there was no correlation between changes in
      AAG levels and enzymatic activity. We found AAG to be nitrated in human adenomas,
      suggesting that this RNS modification is relevant in the human disease.
      Expression of key downstream components of BER, apurinic/apyrimidinic
      endonuclease 1 (APE1) and DNA polymerase beta (POLbeta), was also examined.
      POLbeta protein was increased in nearly all adenomas compared with adjacent non
      tumor tissues, whereas APE1 expression was only increased in approximately half
      of the adenomas and also was relocalized to the cytoplasm in adenomas.
      Collectively, the results suggest that BER is dysregulated in colon adenomas. RNS
      induced posttranslational modification of AAG is one mechanism of BER
      dysregulation, and the type of modification may define the role of AAG during
      carcinogenesis.

PMID- 19864474
TI  - Adherence factors in atypical enteropathogenic Escherichia coli strains
      expressing the localized adherence-like pattern in HEp-2 cells.
AB  - Although atypical enteropathogenic Escherichia coli (aEPEC) strains are
      frequently implicated in childhood diarrhea in developing countries, not much is
      known about their adherence properties. The phenotypic and genotypic
      characterization of 29 aEPEC strains expressing the localized adherence-like
      pattern points toward the involvement of E. coli common pilus (ECP), intimins,
      and other known E. coli adhesins in this pattern.

PMID- 19864475
TI  - Abundance of multiple high-risk human papillomavirus (HPV) infections found in
      cervical cells analyzed by use of an ultrasensitive HPV genotyping assay.
AB  - PCR methods enable the detection of a large variety of human papillomavirus (HPV)
      genotypes that infect the anogenital tract. However, PCR with consensus primers,
      general primers, and, to a lesser extent, broad-spectrum primers may
      underrepresent the true prevalence of HPV, especially the true prevalence of
      multiple infections. We compared the rate of HPV positivity determined by a broad
      spectrum PCR with primers BSGP5+ and BSGP6+ (BS-PCR) coupled to an established
      bead-based multiplex HPV genotyping (MPG) assay with the rate of HPV positivity
      determined by a multiplex PCR with type-specific primers (TS-PCR) coupled to a
      newly developed MPG assay for 735 selected cervical scraping samples. While the
      primers used for the BS-PCR are located within the L1 region of the HPV genome,
      the primers used for the TS-PCR target the E7 gene. The overall rates of
      positivity for the 19 HPV types included in both assays were 60.9% and 72.2% by
      the BS-PCR and the TS-PCR, respectively, and the two assays found multiple
      infections in 34.8% and 58.0% of the specimens, respectively. Both HPV detection
      assays allowed the semiquantitative detection of HPV types and identified the
      same dominant HPV type in 66.6% of the multiple infections. In conclusion, the TS
      PCR-MPG assay significantly increased the rate of detection of HPV DNA and the
      number of infections with multiple HPV types detected and demonstrated that the
      prevalence of low-copy-number HPV infections in the anogenital tract may be
      strongly underestimated by conventional HPV amplification methods, especially in
      cases of multiple infections. As a consequence, PCR-TS-MPG appears to be highly
      suited for analysis of the significance of multiple infections in the development
      of cervical cancer and for the study the natural history and the latency of HPV.

PMID- 19864476
TI  - Denmark14-230 clone as an increasing cause of pneumococcal infection in Portugal
      within a background of diverse serotype 19A lineages.
AB  - Pneumococci of serotype 19A are increasingly found to be the cause of infection
      in various geographic regions. We have characterized the serotype 19A isolates (n
      = 288) found among pneumococci responsible for infections (n = 1,925) and
      pneumococci recovered from asymptomatic carriers (n = 1,973) in Portugal between
      2001 and 2006. We show that despite the existence of serotype 19A clones that
      have a greater potential to cause invasive disease or an enhanced colonization
      capacity, the lineage that is increasing as a cause of infection in Portugal is a
      multiresistant clone that is competent at both. The expanding Denmark(14)-230
      clone found in Portugal is disseminated in other Mediterranean countries, where
      it is also increasingly responsible for invasive infections in both children and
      adults. The lineages driving the rise of serotype 19A infections in Asia and the
      United States (sequence type 320 [ST320] and ST199) are either absent or account
      for only a small proportion of isolates in Portugal. These data highlight the
      importance of locally circulating clones with the ability to compete in the
      nasopharyngeal niche in the emergence of the serotype 19A lineages which are an
      increasing cause of infection in various geographic regions.

PMID- 19864477
TI  - Diversity of human parechoviruses isolated from stool samples collected from Thai
      children with acute gastroenteritis.
AB  - A total of 82 fecal specimens which were known to be negative for rotavirus,
      adenovirus, norovirus, sapovirus, and astrovirus and which were collected from
      infants and children with acute gastroenteritis in Chiang Mai, Thailand, from
      January to December 2005 were screened for human parechovirus (HPeV). HPeV was
      detected by reverse transcription-PCR with a primer pair that amplified the 5'
      untranslated region of its genome and was genotyped by sequencing of the VP1
      region. HPeV was detected in 12 of 82 specimens tested, and the detection rate
      was found to be 14.6%. The capsid VP1 gene was successfully sequenced from nine
      of the HPeV strains detected. The HPeV strains studied clustered into four
      different genotypes, HPeV genotype 1 (HPeV1) to HPeV4, and the majority of the
      strains studied (five strains) belonged to HPeV1. This is the first finding of
      HPeV from children with acute gastroenteritis in Thailand. In addition, the
      diversity of the Thai HPeV strains was also noted.

PMID- 19864478
TI  - Clinical significance of Mycobacterium asiaticum isolates in Queensland,
      Australia.
AB  - Mycobacterium asiaticum was first reported as a cause of human disease in 1982,
      with only a few cases in the literature to date. This study aims to review the
      clinical significance of M. asiaticum isolates in Queensland, Australia. A
      retrospective review (1989 to 2008) of patients with M. asiaticum isolates was
      conducted. Data were collected through the Queensland TB Control Centre database.
      Disease was defined in accordance with the American Thoracic Society criteria.
      Twenty-four patients (13 female) had a positive culture of M. asiaticum, many
      residing around the Tropic of Capricorn. M. asiaticum was responsible for
      pulmonary disease (n = 2), childhood lymphadenitis (n = 1), olecranon bursitis (n
      = 1), 6 cases of possible pulmonary disease, and 2 possible wound infections.
      Chronic lung disease was a risk factor for pulmonary infection, and
      wounds/lacerations were a risk factor for extrapulmonary disease. Extrapulmonary
      disease responded to local measures. Pulmonary disease responded to ethambutol
      isoniazid-rifampin plus pyrazinamide for the first 2 months in one patient, and
      amikacin-azithromycin-minocycline in another patient. While M. asiaticum is rare
      in Queensland, there appears to be an environmental niche. Although often a
      colonizer, it can be a cause of pulmonary and extrapulmonary disease. Treatment
      of pulmonary disease remains challenging. Extrapulmonary disease does not mandate
      specific nontuberculous mycobacterium (NTM) treatment.

PMID- 19864479
TI  - Comparison of BD GeneOhm Cdiff real-time PCR assay with a two-step algorithm and
      a toxin A/B enzyme-linked immunosorbent assay for diagnosis of toxigenic
      Clostridium difficile infection.
AB  - The BD GeneOhm Cdiff assay, a real-time PCR assay for the detection of the
      Clostridium difficile toxin B (tcdB) gene, was compared with the toxin A/B (Tox
      A/B) II enzyme-linked immunosorbent assay (ELISA) and a two-step algorithm which
      includes a C. Diff Chek-60 glutamate dehydrogenase (GDH) antigen assay followed
      by cytotoxin neutralization. Four hundred liquid or semisolid stool samples
      submitted for diagnostic C. difficile testing, 200 GDH antigen positive and 200
      GDH antigen negative, were selected for analysis. All samples were tested by the
      C. Diff Chek-60 GDH antigen and cytotoxin neutralization assays, the Tox A/B II
      ELISA, and the BD GeneOhm Cdiff assay. Specimens with discrepant results were
      tested by toxigenic culture as an independent "gold standard." Of 200 GDH
      positive samples, 71 were positive by the Tox A/B II ELISA, 88 were positive by
      the two-step method, 93 were positive by PCR, and 96 were positive by the GDH
      antigen assay only. Of 200 GDH-negative samples, 3 were positive by PCR only.
      Toxigenic culture was performed for 41 samples with discrepant results, and 39
      were culture positive. Culture resolution of discrepant results showed the Tox
      A/B II assay to have detected 70 (66.7%), the two-step method to have detected 87
      (82.9%), and PCR to have detected 96 (91.4%) of 105 true positives. The BD
      GeneOhm Cdiff assay was more sensitive in detecting toxigenic C. difficile than
      the Tox A/B II assay (P < 0.0001); however, the difference between PCR and the
      two-step method was not significant (P = 0.1237). Enhanced sensitivity and rapid
      turnaround time make the BD GeneOhm Cdiff assay an important advance in the
      diagnosis of toxigenic C. difficile infection.

PMID- 19864480
TI  - Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of
      on-demand, near-patient technology.
AB  - Current nucleic acid amplification methods to detect Mycobacterium tuberculosis
      are complex, labor-intensive, and technically challenging. We developed and
      performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay, an
      integrated hands-free sputum-processing and real-time PCR system with rapid on
      demand, near-patient technology, to simultaneously detect M. tuberculosis and
      rifampin resistance. Analytic tests of M. tuberculosis DNA demonstrated a limit
      of detection (LOD) of 4.5 genomes per reaction. Studies using sputum spiked with
      known numbers of M. tuberculosis CFU predicted a clinical LOD of 131 CFU/ml.
      Killing studies showed that the assay's buffer decreased M. tuberculosis
      viability by at least 8 logs, substantially reducing biohazards. Tests of 23
      different commonly occurring rifampin resistance mutations demonstrated that all
      23 (100%) would be identified as rifampin resistant. An analysis of 20
      nontuberculosis mycobacteria species confirmed high assay specificity. A small
      clinical validation study of 107 clinical sputum samples from suspected
      tuberculosis cases in Vietnam detected 29/29 (100%) smear-positive culture
      positive cases and 33/39 (84.6%) or 38/53 (71.7%) smear-negative culture-positive
      cases, as determined by growth on solid medium or on both solid and liquid media,
      respectively. M. tuberculosis was not detected in 25/25 (100%) of the culture
      negative samples. A study of 64 smear-positive culture-positive sputa from
      retreatment tuberculosis cases in Uganda detected 63/64 (98.4%) culture-positive
      cases and 9/9 (100%) cases of rifampin resistance. Rifampin resistance was
      excluded in 54/55 (98.2%) susceptible cases. Specificity rose to 100% after
      correcting for a conventional susceptibility test error. In conclusion, this
      highly sensitive and simple-to-use system can detect M. tuberculosis directly
      from sputum in less than 2 h.

PMID- 19864481
TI  - Multiplex PCR-ligation detection reaction assay for simultaneous detection of
      drug resistance and toxin genes from Staphylococcus aureus, Enterococcus
      faecalis, and Enterococcus faecium.
AB  - A multiplex PCR-ligation detection reaction (PCR-LDR) assay was developed for
      rapid detection of methicillin, tetracycline, and vancomycin resistance, as well
      as toxic shock toxin and Panton-Valentine leukocidin. The assay was tested on 470
      positive blood culture bottles containing Staphylococcus aureus or enterococci.
      PCR-LDR exhibited a sensitivity and specificity of > or = 98% for all components
      except tetracycline resistance, which had a sensitivity of 94.7%. Rapid and
      sensitive detection of antimicrobial resistance and virulence genes could help
      guide therapy and appropriate infection control measures.

PMID- 19864482
TI  - Molecular epidemiology of genogroup II-genotype 4 noroviruses in the United
      States between 1994 and 2006.
AB  - Human noroviruses (NoVs) of genogroup II, genotype 4 (GII.4) are the most common
      strains detected in outbreaks of acute gastroenteritis worldwide. To gain insight
      into the epidemiology and genetic variation of GII.4 strains, we analyzed 773 NoV
      outbreaks reported to the CDC from 1994 to 2006. Of these NoV outbreaks, 629
      (81.4%) were caused by GII viruses and 342 (44.2%) were caused by GII.4 strains.
      The proportion of GII.4 outbreaks increased from 5% in 1994 to 85% in 2006, but
      distinct annual differences were noted, including sharp increases in 1996, 2003,
      and 2006 each associated with newly emerging GII.4 strains. Sequence analysis of
      the full-length VP1 gene of GII.4 strains identified in this study and from
      GenBank segregated these viruses into at least 9 distinct subclusters which had
      1.3 to 3.2% amino acid variation between strains in different subclusters. We
      propose that GII.4 subclusters be defined as having >5% sequence variation
      between strains. Our data confirm other studies on the rapid emergence and
      displacement of highly virulent GII.4 strains.

PMID- 19864483
TI  - Gamma-aminobutyric acid and glutamate differentially regulate intracellular
      calcium concentrations in mouse gonadotropin-releasing hormone neurons.
AB  - Multiple factors regulate the activity of the GnRH neurons responsible for
      controlling fertility. Foremost among neuronal inputs to GnRH neurons are those
      using the amino acids glutamate and gamma-aminobutyric acid (GABA). The present
      study used a GnRH-Pericam transgenic mouse line, enabling live cell imaging of
      intracellular calcium concentrations ([Ca(2+)](i)) to evaluate the effects of
      glutamate and GABA signaling on [Ca(2+)](i) in peripubertal and adult mouse GnRH
      neurons. Activation of GABA(A), N-methyl-d-aspartate, or alpha-amino-3-hydroxyl-5
      methyl-4-isoxazole propionate acid (AMPA) receptors was found to evoke an
      increase in [Ca(2+)](i), in subpopulations of GnRH neurons. Approximately 70% of
      GnRH neurons responded to GABA, regardless of postnatal age or sex. Many fewer
      (approximately 20%) GnRH neurons responded to N-methyl-d-aspartate, and this was
      not influenced by postnatal age or sex. In contrast, about 65% of adult male and
      female GnRH neurons responded to AMPA compared with about 14% of male and female
      peripubertal mice (P < 0.05). The mechanisms underlying the ability of GABA and
      AMPA to increase [Ca(2+)](i) in adult GnRH neurons were evaluated
      pharmacologically. Both GABA and AMPA were found to evoke [Ca(2+)](i) increases
      through a calcium-induced calcium release mechanism involving internal calcium
      stores and inositol-1,4,5-trisphosphate receptors. For GABA, the initial increase
      in [Ca(2+)](i) originated from GABA(A) receptor-mediated activation of L-type
      voltage-gated calcium channels, whereas for AMPA this appeared to involve direct
      calcium entry through the AMPA receptor. These observations show that all of the
      principal amino acid receptors are able to control [Ca(2+)](i) in GnRH neurons
      but that they do so in a postnatal age- and intracellular pathway-specific
      manner.

PMID- 19864484
TI  - High-voltage electron microscopy reveals direct synaptic inputs from a spinal
      gastrin-releasing peptide system to neurons of the spinal nucleus of
      bulbocavernosus.
AB  - The spinal nucleus of bulbocavernosus (SNB) is a sexually dimorphic motor nucleus
      located in the anterior horn of the fifth and sixth lumbar segments of the spinal
      cord that plays a significant role in male sexual function. We recently found
      that a sexually dimorphic expression of gastrin-releasing peptide (GRP) in the
      lumbar spinal cord regulates male copulatory reflexes. Although it is reported
      that these systems are both profoundly regulated by circulating androgen levels
      in male rats, no direct evidence has been reported regarding GRP synaptic inputs
      onto SNB motoneurons. The aim of the current study was to determine the
      axodendritic synaptic inputs of spinal GRP neurons to SNB motoneurons.
      Immunoelectron microscopy, combined with a retrograde tracing technique using
      high-voltage electron microscopy (HVEM), provided a three-dimensional
      visualization of synaptic contacts from the GRP system in the lumbar spinal cord
      onto SNB motoneurons. HVEM analysis clearly demonstrated that GRP-immunoreactive
      axon terminals directly contact dendrites that extend into the dorsal gray
      commissure from the SNB. These HVEM findings provide an ultrastructural basis for
      understanding how the spinal GRP system regulates male sexual behavior.

PMID- 19864485
TI  - Development and analytical validation of an immunoassay for quantifying serum
      anti-pertussis toxin antibodies resulting from Bordetella pertussis infection.
AB  - Adequately sensitive and specific methods to diagnose pertussis in adolescents
      and adults are not widely available. Currently, no Food and Drug Administration
      approved diagnostic assays are available for the serodiagnosis of Bordetella
      pertussis. Since concentrations of B. pertussis-specific antibodies tend to be
      high during the later phases of disease, a simple, rapid, easily transferable
      serodiagnostic test was developed. This article describes test development,
      initial evaluation of a prototype kit enzyme-linked immunosorbent assay (ELISA)
      in an interlaboratory collaborative study, and analytical validation. The data
      presented here demonstrate that the kit met all prespecified criteria for
      precision, linearity, and accuracy for samples with anti-pertussis toxin (PT)
      immunoglobulin G (IgG) antibody concentrations in the range of 50 to 150 ELISA
      units (EU)/ml, the range believed to be most relevant for serodiagnosis. The
      assay met the precision and linearity criteria for a wider range, namely, from 50
      to 200 EU/ml; however, the accuracy criterion was not met at 200 EU/ml. When the
      newly adopted World Health Organization International Standard for pertussis
      antiserum (human) reference reagent was used to evaluate accuracy, the accuracy
      criteria were met from 50 to 200 international units/ml. In conclusion, the IgG
      anti-PT ELISA met all assay validation parameters within the range considered
      most relevant for serodiagnosis. This ELISA was developed and analytically
      validated as a user-friendly kit that can be used in both qualitative and
      quantitative formats. The technology for producing the kit is transferable to
      public health laboratories.

PMID- 19864486
TI  - Peptide microarray-based identification of Mycobacterium tuberculosis epitope
      binding to HLA-DRB1*0101, DRB1*1501, and DRB1*0401.
AB  - A more effective vaccine against Mycobacterium tuberculosis is needed, and a
      number of M. tuberculosis vaccine candidates are currently in preclinical or
      clinical phase I and II studies. One of the strategies to select M. tuberculosis
      (protein) targets to elicit a CD8(+) or CD4(+) T-cell response is to gauge the
      binding of candidate peptides to major histocompatibility complex (MHC) class I
      or class II molecules, a prerequisite for successful peptide presentation and to
      expand antigen-specific T cells. We scanned 61 proteins from the M. tuberculosis
      proteome for potential MHC class II-presented epitopes that could serve as
      targets for CD4(+) T-cell responses. We constructed a peptide microarray
      consisting of 7,466 unique peptides derived from 61 M. tuberculosis proteins. The
      peptides were 15-mers overlapping by 12 amino acids. Soluble recombinant
      DRB1*0101 (DR1), DRB1*1501 (DR2), and DRB1*0401 (DR4) monomers were used to gauge
      binding to individual peptide species. Out of 7,466 peptides, 1,282, 674, and
      1,854 peptides formed stable complexes with HLA-DR1, -DR2, and -DR4,
      respectively. Five hundred forty-four peptides bound to all three MHC class II
      molecules, 609 bound to only two, and 756 bound to only a single MHC class II
      molecule. This allowed us to rank M. tuberculosis proteins by epitope density. M.
      tuberculosis proteins contained "hot spots," i.e., regions with enriched MHC
      class II binding epitopes. Two hundred twenty-two peptides that formed MHC class
      II-peptide complexes had previously been described as exclusively recognized by
      IgG in sera from patients with active pulmonary tuberculosis, but not in sera
      from healthy individuals, suggesting that these peptides serve as B-cell and
      CD4(+) T-cell epitopes. This work helps to identify not only M. tuberculosis
      peptides with immunogenic potential, but also the most immunogenic proteins. This
      information is useful for vaccine design and the development of future tools to
      explore immune responses to M. tuberculosis.

PMID- 19864487
TI  - Intranasal immunization of mice with a bovine respiratory syncytial virus vaccine
      induces superior immunity and protection compared to those by subcutaneous
      delivery or combinations of intranasal and subcutaneous prime-boost strategies.
AB  - Bovine respiratory syncytial virus (BRSV) infects cells of the respiratory
      mucosa, so it is desirable to develop a vaccination strategy that induces mucosal
      immunity. To achieve this, various delivery routes were compared for formalin
      inactivated (FI) BRSV formulated with CpG oligodeoxynucleotide (ODN) and
      polyphosphazene (PP). Intranasal delivery of the FI-BRSV formulation was superior
      to subcutaneous delivery in terms of antibody, cell-mediated, and mucosal immune
      responses, as well as reduction in virus replication after BRSV challenge.
      Although intranasal delivery of FI-BRSV also induced higher serum and lung
      antibody titers and gamma interferon (IFN-gamma) production in the lungs than
      intranasal-subcutaneous and/or subcutaneous-intranasal prime-boost strategies, no
      significant differences were observed in cell-mediated immune responses or virus
      replication in the lungs of challenged mice. Interleukin 5 (IL-5), eotaxin, and
      eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously
      immunized mice compared to unvaccinated mice, but not in the lungs of mice
      immunized intranasally or through combinations of the intranasal and subcutaneous
      routes. These results suggest that two intranasal immunizations with FI-BRSV
      formulated with CpG ODN and PP are effective and safe as an approach to induce
      systemic and mucosal responses, as well to reduce virus replication after BRSV
      challenge. Furthermore, intranasal-subcutaneous and subcutaneous-intranasal prime
      boost strategies were also safe and almost as efficacious. In addition to the
      implications for the development of a protective BRSV vaccine for cattle,
      formulation with CpG ODN and PP could also prove important in the development of
      a mucosal vaccine that induces protective immunity against human RSV.

PMID- 19864488
TI  - Disordered aldosterone-volume relationship in end-stage kidney disease.
AB  - INTRODUCTION: Sodium loading, and subsequent volume expansion, suppresses
      aldosterone levels in individuals with normal renal function. We hypothesised
      that loss of renal function impairs this volume-aldosterone relationship.
      MATERIALS AND METHODS: With multifrequency bioimpedance spectroscopy, we measured
      total body water (TBW), extracellular volume (ECV), and intracellular volume in
      five haemodialysis patients at varied states of hydration and in five healthy
      volunteers during low-, normal-, and high-salt diets. Serum aldosterone,
      potassium, and C-reactive protein were measured simultaneously. Scatterplots and
      general estimating equations were used to examine the relationship among these
      variables. RESULTS: In healthy volunteers with salt loading, and in haemodialysis
      subjects with increased inter-dialytic weight gain, expansion of ECV led to
      reciprocal declines in serum aldosterone concentrations. The relationship was
      more profound in healthy volunteers (p<0.001) than in haemodialysis subjects
      (p=0.1). Notably, haemodialysis subjects posted consistently higher levels of ECV
      (median 49.6% TBW, IQR 43.9-51.8% compared to 41.1%, 39.9-42.8% in volunteers)
      and serum aldosterone (median 26.7 ng/dl, IQR 19.8-29.6 compared to 12.4 ng/dl,
      8.8-16.0 in volunteers). Serum potassium did not appear to influence aldosterone
      concentration (p=0.9). CONCLUSIONS: The shift of the volume-aldosterone curve in
      haemodialysis subjects suggests that end-stage kidney disease is a state of high
      volume and inappropriately high aldosterone. These data have important clinical
      implications, as dialysis patients may benefit from both volume reduction and
      mineralocorticoid receptor blockade.

PMID- 19864489
TI  - Fibroblast phenotype in male carriers of FMR1 premutation alleles.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset
      neurodegenerative disorder among carriers of premutation expansions (55-200 CGG
      repeats) of the fragile X mental retardation 1 (FMR1) gene. The clinical features
      of FXTAS, as well as various forms of clinical involvement in carriers without
      FXTAS, are thought to arise through a direct toxic gain of function of high
      levels of FMR1 mRNA containing the expanded CGG repeat. Here we report a cellular
      endophenotype involving increased stress response (HSP27, HSP70 and CRYAB) and
      altered lamin A/C expression/organization in cultured skin fibroblasts from 11
      male carriers of premutation alleles of the FMR1 gene, including six patients
      with FXTAS and five premutation carriers with no clinical evidence of FXTAS,
      compared with six controls. A similar abnormal cellular phenotype was found in
      CNS tissue from 10 patients with FXTAS. Finally, there is an analogous abnormal
      cellular distribution of lamin A/C isoforms in knock-in mice bearing the expanded
      CGG repeat in the murine Fmr1 gene. These alterations are evident even in mouse
      embryonic fibroblasts, raising the possibility that, in humans, the expanded
      repeat mRNA triggers pathogenic mechanisms early in development, thus providing a
      molecular basis for the neurodevelopmental abnormalities observed in some
      children and clinical symptoms in some adults who are carriers of premutation
      FMR1 alleles. Cellular dysregulation in fibroblasts represents a novel and highly
      advantageous model for investigating disease pathogenesis in premutation carriers
      and for quantifying and monitoring disease progression. Fibroblast studies may
      also prove useful in screening and testing the efficacy of therapeutic
      interventions.

PMID- 19864490
TI  - Consortin, a trans-Golgi network cargo receptor for the plasma membrane targeting
      and recycling of connexins.
AB  - Targeting of numerous transmembrane proteins to the cell surface is thought to
      depend on their recognition by cargo receptors that interact with the adaptor
      machinery for anterograde traffic at the distal end of the Golgi complex. We
      report here on consortin, a novel integral membrane protein that is predicted to
      be intrinsically disordered, i.e. that contains large segments whose native state
      is unstructured. We identified consortin as a binding partner of connexins, the
      building blocks of gap junctions. Consortin is located at the trans-Golgi network
      (TGN), in tubulovesicular transport organelles, and at the plasma membrane. It
      directly interacts with the TGN clathrin adaptors GGA1 and GGA2, and disruption
      of this interaction by expression of a consortin mutant lacking the acidic
      cluster-dileucine (DXXLL) GGA interaction motif causes an intracellular
      accumulation of several connexins. RNA interference-mediated silencing of
      consortin expression in HeLa cells blocks the cell surface targeting of these
      connexins, which accumulate intracellularly, whereas partial depletion and
      redistribution of the consortin pool slows down the intracellular degradation of
      gap junction plaques. Altogether, our results show that, by studying connexin
      trafficking, we have identified the first TGN cargo receptor for the targeting of
      transmembrane proteins to the plasma membrane. The identification of consortin
      provides in addition a potential target for therapies aimed at diseases in which
      connexin traffic is altered, including cardiac ischemia, peripheral neuropathies,
      cataracts and hearing impairment. Sequence accession numbers. GenBank: Human CNST
      cDNA, NM_152609; mouse Cnst cDNA, NM_146105.

PMID- 19864491
TI  - Nesprin 1 is critical for nuclear positioning and anchorage.
AB  - Nesprin 1 is an outer nuclear membrane protein that is thought to link the
      nucleus to the actin cytoskeleton. Recent data suggest that mutations in Nesprin
      1 may also be involved in the pathogenesis of Emery-Dreifuss muscular dystrophy.
      To investigate the function of Nesprin 1 in vivo, we generated a mouse model in
      which all isoforms of Nesprin 1 containing the C-terminal spectrin-repeat region
      with or without KASH domain were ablated. Nesprin 1 knockout mice are marked by
      decreased survival rates, growth retardation and increased variability in body
      weight. Additionally, nuclear positioning and anchorage are dysfunctional in
      skeletal muscle from knockout mice. Physiological testing demonstrated no
      significant reduction in stress production in Nesprin 1-deficient skeletal muscle
      in either neonatal or adult mice, but a significantly lower exercise capacity in
      knockout mice. Nuclear deformation testing revealed ineffective strain
      transmission to nuclei in muscle fibers lacking Nesprin 1. Overall, our data show
      that Nesprin 1 is essential for normal positioning and anchorage of nuclei in
      skeletal muscle.

PMID- 19864492
TI  - Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal
      anomalies.
AB  - Ocular mal-development results in heterogeneous and frequently visually disabling
      phenotypes that include coloboma and microphthalmia. Due to the contribution of
      bone morphogenetic proteins to such processes, the function of the paralogue
      Growth Differentiation Factor 3 was investigated. Multiple mis-sense variants
      were identified in patients with ocular and/or skeletal (Klippel-Feil) anomalies
      including one individual with heterozygous alterations in GDF3 and GDF6. These
      variants were characterized, individually and in combination, through integrated
      biochemical and zebrafish model organism analyses, demonstrating appreciable
      effects with western blot analyses, luciferase based reporter assays and
      antisense morpholino inhibition. Notably, inhibition of the zebrafish co
      orthologue of GDF3 accurately recapitulates patient phenotypes. By demonstrating
      the pleiotropic effects of GDF3 mutation, these results extend the contribution
      of perturbed BMP signaling to human disease and potentially implicate multi
      allelic inheritance of BMP variants in developmental disorders.

PMID- 19864494
TI  - Trust me, I am a policy maker.

PMID- 19864493
TI  - Sporadic ALS has compartment-specific aberrant exon splicing and altered cell
      matrix adhesion biology.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by progressive weakness from loss of motor neurons. The fundamental
      pathogenic mechanisms are unknown and recent evidence is implicating a
      significant role for abnormal exon splicing and RNA processing. Using new
      comprehensive genomic technologies, we studied exon splicing directly in 12
      sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy
      system that processed nervous systems specifically for genomic studies. ALS
      patients had rostral onset and caudally advancing disease and abundant residual
      motor neurons in this region. We created two RNA pools, one from motor neurons
      collected by laser capture microdissection and one from the surrounding anterior
      horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon
      splicing, and applied advanced bioinformatics. We employed rigorous quality
      control measures at all steps and validated findings by qPCR. In the motor neuron
      enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which
      were up-regulated: 148 differentially expressed genes (P <or= 10(-3)) and 411
      aberrantly spliced genes (P <or= 10(-5)). The aberrantly spliced genes were
      highly enriched in cell adhesion (P <or= 10(-57)), especially cell-matrix as
      opposed to cell-cell adhesion. Most of the enriching genes encode transmembrane
      or secreted as opposed to nuclear or cytoplasmic proteins. The differentially
      expressed genes were not biologically enriched. In the anterior horn enriched
      mRNA pool, we could not clearly identify mRNA signals or biological enrichment.
      These findings, perturbed and up-regulated cell-matrix adhesion, suggest possible
      mechanisms for the contiguously progressive nature of motor neuron degeneration.
      Data deposition: GeneChip raw data (CEL-files) have been deposited for public
      access in the Gene Expression Omnibus (GEO), www.ncbi.nlm.nih.gov/geo, accession
      number GSE18920.

PMID- 19864495
TI  - The association between perceived interpersonal social support and physical and
      mental health: results from the National Epidemiological Survey on Alcohol and
      Related Conditions.
AB  - BACKGROUND: Low social support has been associated with several disorders. We
      test the relationship between perceived interpersonal social support (ISS) and
      aspects of mental and physical health. METHODS: We used data from National
      Epidemiological Survey on Alcohol and Related Conditions in which 34,653
      individuals aged 20-99 years were interviewed twice (2001-02 and 2004-05), with
      the second interview including the interpersonal support evaluation list. The
      association of perceived ISS with lifetime DSM-IV psychopathology and physical
      health from the past 12 months was investigated. We also tested whether this
      association changes as a function of number of traumatic events in accordance
      with the buffering hypothesis. RESULTS: Low perceived ISS correlated with
      increased prevalence of major depressive disorder, generalized anxiety, social
      phobia and several physical health problems. There was a strong association
      between excellent self-perceived physical health and high social support.
      CONCLUSIONS: There was evidence for both the main, beneficial effects of high
      perceived ISS and buffering, whereby increased perceived ISS ameliorated the
      pathogenic influence of exposure to traumatic life events on psychopathology.
      Current findings highlight the importance of perceived ISS in individuals'
      general mental and physical well-being, both in daily life and upon exposure to
      negative life events.

PMID- 19864497
TI  - Trust, terrorism and public health.
AB  - Policies to promote public health are based on trust. There is a danger that
      public trust may be lost, especially where policies are seen to be influenced by
      vested interests or conflict with available evidence. Although trust in public
      health policies in the UK is high, some commentators have questioned recent
      responses to the threat of pandemic flu, suggesting that they may be driven, in
      part, by those seeking to profit from health scares, and drawing a direct
      comparison with terrorist scares. We argue that the approach to evidence by the
      public health and counter-terrorist communities differ markedly. Public health
      professionals must ensure that their actions do not undermine their credibility,
      in particular those involved in response to the threat of bioterrorism.

PMID- 19864496
TI  - Evaluation of a cardiovascular disease opportunistic risk assessment pilot
      ('Heart MOT' service) in community pharmacies.
AB  - BACKGROUND: Cardiovascular risk-based screening is proposed as a key intervention
      to reduce premature cardiovascular disease (CVD) in the UK and internationally.
      This study evaluated a targeted cardiovascular (CVD) assessment pilot in 23
      community pharmacies in Birmingham, UK. METHODS: The CVD risk assessment service
      used near-patient testing and the Framingham risk equations administered by
      pharmacists to screen clients aged 40-70 without known CVD. Outcomes assessed
      included volume of activity, uptake by deprivation and ethnicity and onwards
      referral. RESULTS: Complete data were available for 1130 of 1141 clients; 679
      (60%) male, 218 (19%) smokers and 124 (11%) had a family history of CVD. Overall,
      792 (70%) of clients were referred to their general practice: 201 (18%) at CVD
      risk of 20% or more, remainder with individual risk factor(s). Greater
      representation from Black (7.4%) and Asian (24.8%) communities and from average
      and less deprived quintiles than the affluent and most deprived was observed.
      CONCLUSIONS: Community pharmacies can provide a CVD risk assessment service in a
      UK urban setting that can attract males and provide access for deprived
      communities and Black and Asian communities. A pharmacy service can support GP
      practices in identifying and managing the workload of around 30% of clients.

PMID- 19864498
TI  - Could it be asthma? Using social marketing strategies to increase parent and
      caregiver knowledge of asthma symptoms in children in a rural community.
AB  - Many parents and caregivers do not recognize the symptoms of asthma in children,
      and consequently children may not receive the appropriate diagnosis and treatment
      for this potentially fatal disease. This article describes how Steps to a
      HealthierNY used social marketing strategies to design a media campaign called
      "Could It Be Asthma?" to educate parents and caregivers about the symptoms of
      asthma. The campaign used television advertising, brochures, and posters to
      educate parents and caregivers in rural Jefferson County, New York, about asthma
      symptoms. The campaign ran in March and April 2005. A follow-up survey was
      conducted among 756 parents and caregivers in collaboration with four local
      pediatricians' offices. Results showed that approximately 60% of participants
      were familiar with "Could It Be Asthma?" Of those participants, approximately 68%
      indicated that the ads had a positive impact and 46% indicated that they had
      learned the symptoms of asthma. The campaign and survey were repeated in the fall
      of 2005. Results were consistent, with a significant increase in the percentage
      of people who were familiar with the campaign. This social marketing campaign was
      successful in reaching parents in a rural community with important educational
      messages; similar strategies should be considered in educating the public about
      asthma and other health issues.

PMID- 19864500
TI  - Roles of the ERK MAPK in the regulation of proinflammatory and apoptotic
      responses in chicken macrophages infected with H9N2 avian influenza virus.
AB  - The mitogen-activated protein kinase (MAPK) family is responsible for important
      signalling pathways which regulate cell activation, differentiation, apoptosis
      and immune responses. Studies have shown that influenza virus infection activates
      MAPK family members in mammals. While the extracellular signal-regulated kinase
      (ERK)1/2 is important for virus replication, activation of p38 controls the
      expression of RANTES, interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha.
      In this study, we report that avian influenza virus (AIV) activates ERK, p38 and
      Jun-N-terminal kinases in avian species. In chicken macrophages, while ERK was
      required for H9N2 AIV replication, ERK regulated proinflammatory cytokines IL
      1beta, IL-6 and IL-8, which is distinct from what has been previously reported in
      mammalian cells. Moreover, ERK alone suppressed TNF-alpha and FasL and inhibited
      TNF-family-mediated extrinsic apoptosis in H9N2-infected chicken macrophages.
      Taken together, these findings suggest that ERK signalling may uniquely play
      important roles in avian host responses to AIV infection.

PMID- 19864499
TI  - Inhibition of the phosphatidylinositol 3-kinase-Akt pathway enhances gamma-2
      herpesvirus lytic replication and facilitates reactivation from latency.
AB  - Cellular signalling pathways are critical in regulating the balance between
      latency and lytic replication of herpesviruses. Here, we investigated the effect
      of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway on replication of two
      gamma-2 herpesviruses, murine gammaherpesvirus-68 (MHV-68) and human herpesvirus
      8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). We found that de novo
      infection of MHV-68 induced PI3K-dependent Akt activation and the lytic
      replication of MHV-68 was enhanced by inhibiting the PI3K-Akt pathway with both
      chemical inhibitors and RNA interference technology. Inhibiting the activity of
      Akt using Akt inhibitor VIII also facilitated the reactivation of KSHV from
      latency. Both lytic replication and latency depend on the activity of viral
      transactivator RTA and we further show that the activity of RTA is increased by
      reducing Akt1 expression. The data suggest that the PI3K-Akt pathway suppresses
      the activity of RTA and thereby contributes to the maintenance of viral latency
      and promotes tumorigenesis.

PMID- 19864501
TI  - Evidence for similarity-assisted recombination and predicted stem-loop structure
      determinant in potato virus X RNA recombination.
AB  - Virus RNA recombination, one of the main factors for genetic variability and
      evolution, is thought to be based on different mechanisms. Here, the recently
      described in vivo potato virus X (PVX) recombination assay [Draghici, H.-K. &
      Varrelmann, M. (2009). J Virol 83, 7761-7769] was applied to characterize
      structural parameters of recombination. The assay uses an Agrobacterium-mediated
      expression system incorporating a PVX green fluorescent protein (GFP)-labelled
      full-length clone. The clone contains a partial coat protein (CP) deletion that
      causes defectiveness in cell-to-cell movement, together with a functional CP+3'
      non-translated region (ntr) transcript, in Nicotiana benthamiana leaf tissue. The
      structural parameters assessed were the length of sequence overlap, the distance
      between mutations and the degree of sequence similarity. The effects on the
      observed frequency of reconstitution and the composition of the recombination
      products were characterized. Application of four different type X intact PVX CP
      genes with variable composition allowed the estimation of the junction sites of
      precise homologous recombination. Although one template switch would have been
      sufficient for functional reconstitution, between one and seven template switches
      were observed. Use of PVX-GFP mutants with CP deletions of variable length
      resulted in a linear decrease of the reconstitution frequency. The critical
      length observed for homologous recombination was 20-50 nt. Reduction of the
      reconstitution frequency was obtained when a phylogenetically distant PVX type Bi
      CP gene was used. Finally, the prediction of CP and 3'-ntr RNA secondary
      structure demonstrated that recombination-junction sites were located mainly in
      regions of stem-loop structures, allowing the recombination observed to be
      categorized as similarity-assisted.

PMID- 19864502
TI  - Fast, broad-range disinfection of bacteria, fungi, viruses and prions.
AB  - Effective disinfectants are of key importance for the safe handling and
      reprocessing of surgical instruments. This study tested whether new formulations
      containing SDS, NaOH and 1-propanol (n-propanol) are simultaneously active
      against a broad range of pathogens including bacteria, fungi, non-enveloped
      viruses and prions. Inactivation and disinfection were examined in suspension and
      on carriers, using coagulated blood or brain homogenate as an organic
      contaminant. Coomassie blue staining was used to assess whether the formulations
      undesirably fixed proteins to rough surfaces. A mixture of 0.2 % SDS and 0.3 %
      NaOH in 20 % n-propanol achieved potent decontamination of steel carriers
      contaminated with PrP(TSE), the biochemical marker for prion infectivity, from
      263K scrapie hamsters or from patients with sporadic or variant Creutzfeldt-Jakob
      disease. 263K scrapie infectivity on carriers was decreased by > or =5.5 logs.
      Furthermore, the formulation effectively inactivated poliovirus, hepatitis A
      virus and caliciviruses (including murine norovirus) in suspension tests. It also
      yielded significant titre reductions of bacteria (Enterococcus faecium,
      Mycobacterium avium; >6 logs), fungi (spores of Aspergillus niger; > or =5 logs)
      and poliovirus (>4 logs) embedded in coagulated blood on carriers. The
      formulation was not found to fix proteins more than was observed with water as
      the cleaning reagent. In conclusion, SDS, NaOH and n-propanol can synergistically
      achieve fast, broad-range disinfection.

PMID- 19864503
TI  - Mouse vaccination with dendritic cells loaded with prion protein peptides
      overcomes tolerance and delays scrapie.
AB  - Prion diseases are presumed to be caused by the accumulation in the brain of a
      pathological protein called prion protein (PrP) scrapie which results from the
      transconformation of cellular PrP, a ubiquitous glycoprotein expressed in all
      mammals. Since all isoforms of PrP are perceived as self by the host immune
      system, a major problem in designing efficient immunoprophylaxis or immunotherapy
      is to overcome tolerance. The present study was aimed at investigating whether
      bone-marrow-derived dendritic cells (DCs) loaded with peptides previously shown
      to be immunogenic in PrP-deficient mice, can overcome tolerance in PrP-proficient
      wild-type mice and protect them against scrapie. Results show that, in such mice,
      peptide-loaded DCs elicit both lymphokine release by T cells and antibody
      secretion against native cellular PrP. Repeated recalls with peptide-loaded DCs
      reduces the attack rate of 139A scrapie inoculated intraperitoneally and retards
      disease duration by 40 days. Most interestingly, survival time in individual mice
      appears to be correlated with the level of circulating antibody against native
      cellular PrP.

PMID- 19864504
TI  - Site-specific analysis of N-linked oligosaccharides of recombinant lysosomal
      arylsulfatase A produced in different cell lines.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a
      deficiency of the lysosomal enzyme arylsulfatase A (ASA). Enzyme replacement
      therapy (ERT) is a therapeutic option for MLD and other lysosomal disorders. This
      therapy depends on N-linked oligosaccharide-mediated delivery of intravenously
      injected recombinant enzyme to the lysosomes of patient cells. Because of the
      importance of N-linked oligosaccharide side chains in ERT, we examined the
      composition of the three N-linked glycans of four different recombinant ASAs in a
      site-specific manner. Depending on the culture conditions and the cell line
      expressing the enzyme, we detected a high variability of the high-mannose-type N
      glycans which prevail at all glycosylation sites. Our data show that the
      composition of the glycans is largely determined by substantial trimming in the
      medium. The susceptibility for trimming is different for the glycans at the three
      N-glycosylation sites. Interestingly, which of the glycans is most susceptible to
      trimming also depends on production conditions. CHO cells cultured under
      bioreactor conditions yielded recombinant ASA with the most preserved N-glycan
      structures, the highest mannose-6-phosphate content and the highest similarity to
      non-recombinant enzyme. Notably, roughly one-third of the N-glycans released from
      the three glycosylation sites were fucosylated. In the last years, numerous
      recombinant lysosomal enzymes were used for preclinical ERT trials. Our data show
      that the oligosaccharide structures were very different in these trials making it
      difficult to draw common conclusions from the various investigations.

PMID- 19864505
TI  - Progressive chondrocyte death after impact injury indicates a need for
      chondroprotective therapy.
AB  - BACKGROUND: Impact injury to articular cartilage can lead to posttraumatic
      osteoarthritis. HYPOTHESES: This study tests the hypotheses that (1) chondrocyte
      injury occurs after impact at energies insufficient to fracture the cartilage
      surface, and that (2) cartilage injury patterns vary with impact energy, time
      after injury, and cartilage thickness. STUDY DESIGN: Controlled laboratory study.
      METHODS: Fresh bovine osteochondral cores were randomly divided into 5 groups:
      (1) control, (2) 0.35 J, (3) 0.71 J, (4) 1.07 J, and (5) 1.43 J impact energies.
      Cores were subjected to computer-controlled impact loading and full-thickness
      sections were then prepared and incubated in Dulbecco's Modified Eagle's
      Medium/F12 at 37 degrees C. Adjacent sections were harvested 1 and 4 days after
      impact for viability staining and fluorescent imaging. The area of dead and
      living chondrocytes was quantified using custom image analysis software and
      reported as a percentage of total cartilage area. RESULTS: The highest impact
      energy fractured the cartilage in all cores (1.43 J, n = 17). Seventy-three
      percent and 64% of the osteochondral cores remained intact after lower energy
      impacts of 0.71 J and 1.07 J, respectively. At lower energy levels, fractured
      cores were thinner (P <.01) than those remaining intact. In cores remaining
      intact after impact injury, chondrocyte death increased with increasing impact
      energy (P <.05) and with greater time after impact (P <.05). A progressive
      increase in dead cells near the bone/cartilage interface and at the articular
      surface was observed. CONCLUSION: These data showing progressive chondrocyte
      death after impact injury at energies insufficient to fracture the cartilage
      surface demonstrate a potential need for early chondroprotective therapy.
      CLINICAL RELEVANCE: These data show that efforts to reduce chondrocyte morbidity
      after joint injury may be a useful strategy to delay or prevent the onset of
      posttraumatic osteoarthritis.

PMID- 19864506
TI  - Association of aortic arch pulse wave velocity with left ventricular mass and
      lacunar brain infarcts in hypertensive patients: assessment with MR imaging.
AB  - PURPOSE: To assess the possible association between aortic arch stiffness, which
      may cause hypertensive cardiovascular disease, and cardiac and cerebral end-organ
      damage in patients with hypertension by using magnetic resonance (MR) imaging.
      MATERIALS AND METHODS: Approval from the local institutional review board was
      obtained, and patients gave informed consent. Fifty patients with hypertension
      (31 women and 19 men; mean age +/- standard deviation, 49.2 years +/- 12.7; mean
      systolic blood pressure, 152.1 mm Hg +/- 22.3; mean diastolic blood pressure,
      88.0 mm Hg +/- 13.1), compliant for treatment with antihypertensive medication,
      were prospectively enrolled for MR examinations of the aorta, heart, and brain
      with standard pulse sequences. Aortic arch pulse wave velocity (PWV), left
      ventricular (LV) mass, LV systolic and diastolic function, lacunar brain
      infarcts, and periventricular and deep white matter hyperintensities (WMHs) were
      assessed. Univariable and multiple linear and logistic regression analyses were
      used for statistical analyses. RESULTS: Mean aortic arch PWV was 7.3 m/sec +/-
      2.5. Aortic arch PWV was statistically significantly associated with LV mass (r =
      0.30, P = .03, beta = 1.73); indexes of systolic function, including ejection
      fraction (r = -0.38, P = .01, beta = -1.12); indexes of diastolic function,
      including the ratio of early diastolic to atrial contraction peak filling rates
      (r = -0.44, P < .01, beta = -0.11); lacunar brain infarcts (odds ratio [OR] =
      1.8, P < .01); and periventricular (OR = 1.5, P = .01) and deep (OR = 1.6, P =
      .01) WMHs. Aortic arch PWV was statistically significantly associated with LV
      mass (r = 0.37, P = .03, beta = 2.11) and lacunar brain infarcts (OR = 1.8, P =
      .04), independent of age, sex, and hypertension duration, but not with indexes of
      diastolic and systolic function and WMHs. CONCLUSION: Aortic arch stiffness is
      associated with LV mass and lacunar brain infarcts in hypertensive patients,
      independent of age, sex, and hypertension duration; these manifestations of end
      organ damage may help to risk stratify hypertensive patients.

PMID- 19864507
TI  - Variability in interpretive performance at screening mammography and
      radiologists' characteristics associated with accuracy.
AB  - PURPOSE: To identify radiologists' characteristics associated with interpretive
      performance in screening mammography. MATERIALS AND METHODS: The study was
      approved by institutional review boards of University of Washington (Seattle,
      Wash) and institutions at seven Breast Cancer Surveillance Consortium sites,
      informed consent was obtained, and procedures were HIPAA compliant. Radiologists
      who interpreted mammograms in seven U.S. regions completed a self-administered
      mailed survey; information on demographics, practice type, and experience in and
      perceptions of general radiology and breast imaging was collected. Survey data
      were linked to data on screening mammograms the radiologists interpreted between
      January 1, 1998, and December 31, 2005, and included patient risk factors, Breast
      Imaging Reporting and Data System assessment, and follow-up breast cancer data.
      The survey was returned by 71% (257 of 364) of radiologists; in 56% (205 of 364)
      of the eligible radiologists, complete data on screening mammograms during the
      study period were provided; these data were used in the final analysis. An
      evaluation of whether the radiologists' characteristics were associated with
      recall rate, false-positive rate, sensitivity, or positive predictive value of
      recall (PPV(1)) of the screening examinations was performed with logistic
      regression models that were adjusted for patients' characteristics and
      radiologist-specific random effects. RESULTS: Study radiologists interpreted 1
      036 155 screening mammograms; 4961 breast cancers were detected. Median
      percentages and interquartile ranges, respectively, were as follows: recall rate,
      9.3% and 6.3%-13.2%; false-positive rate, 8.9% and 5.9%-12.8%; sensitivity, 83.8%
      and 74.5%-92.3%; and PPV(1), 4.0% and 2.6%-5.9%. Wide variability in sensitivity
      was noted, even among radiologists with similar false-positive rates. In adjusted
      regression models, female radiologists or fellowship-trained radiologists had
      significantly higher recall and false-positive rates (P < .05, all). Fellowship
      training in breast imaging was the only characteristic significantly associated
      with improved sensitivity (odds ratio, 2.32; 95% confidence interval: 1.42, 3.80;
      P < .001) and the overall accuracy parameter (odds ratio, 1.61; 95% confidence
      interval: 1.05, 2.45; P = .028). CONCLUSION: Fellowship training in breast
      imaging may lead to improved cancer detection, but it is associated with higher
      false-positive rates.

PMID- 19864508
TI  - MR angiography of infrapopliteal arteries in patients with peripheral arterial
      occlusive disease by using Gadofosveset at 3.0 T: diagnostic accuracy compared
      with selective DSA.
AB  - PURPOSE: To prospectively compare the diagnostic accuracy of steady-state, high
      spatial-resolution magnetic resonance (MR) angiography of the lower leg,
      performed with a blood pool contrast agent, with selective digital subtraction
      angiography (DSA) as the reference standard in patients with symptomatic
      peripheral arterial disease. MATERIALS AND METHODS: Local ethics committee
      approval and written informed consent were obtained. In a nonrandomized trial,
      selective DSA and MR angiography were performed at 3.0 T with a blood pool
      contrast agent on 22 calves in 20 patients (mean age, 69.4 years +/- 11.3
      [standard deviation]), 16 men (mean age, 67.8 years +/- 12.4) and four women
      (mean age, 75.6 years +/- 3.6 years), to evaluate 352 arterial segments. DSA and
      MR angiography were performed within 24 hours of each other and directly compared
      by three experienced, blinded radiologists by using high-spatial-resolution
      steady-state MR angiograms. Consensus reading for both DSA and MR angiography
      served as the reference standard. RESULTS: MR angiography was successful and
      occurred without serious adverse events in all patients. Seven significantly
      stenosed and 40 occluded segments were rated equally in both modalities. In three
      cases, the tibial arteries were shown to be occluded or significantly stenosed at
      DSA but appeared normal or significantly stenosed at MR angiography. The
      respective average segment sensitivity, specificity, and accuracy were 98.3% (59
      of 60), 98% (113.7 of 116), and 98.1% (172.7 of 176) for DSA and 100% (60 of 60),
      100% (116 of 116), and 100% (176 of 176) for MR angiography. Steady-state MR
      angiography was especially useful for the distal peroneal artery and the proximal
      anterior tibial artery. CONCLUSION: MR angiography performed with blood pool
      agents has an accuracy comparable with that of selective DSA in the lower leg but
      with less risk involved. Steady-state imaging performed with blood pool agents
      facilitates evaluation of MR angiography of infrapopliteal arteries.

PMID- 19864509
TI  - CT coronary angiography in patients suspected of having coronary artery disease:
      decision making from various perspectives in the face of uncertainty.
AB  - PURPOSE: To determine the cost-effectiveness of computed tomographic (CT)
      coronary angiography as a triage test, performed prior to conventional coronary
      angiography, by using a Markov model. MATERIALS AND METHODS: A Markov model was
      used to analyze the cost-effectiveness of CT coronary angiography performed as a
      triage test prior to conventional coronary angiography from the perspective of
      the patient, physician, hospital, health care system, and society by using
      recommendations from the United Kingdom, the United States, and the Netherlands
      for cost-effectiveness analyses. For CT coronary angiography, a range of
      sensitivities (79%-100%) and specificities (63%-94%) were used to help diagnose
      significant coronary artery disease (CAD). Optimization criteria (ie, outcomes
      considered) were: revised posttest probability of CAD, life-years, quality
      adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios
      (ICERs). Extensive sensitivity analysis was performed. RESULTS: For a prior
      probability of CAD of less than 40%, the probability of CAD after CT coronary
      angiography with negative results was less than 1%. The Markov model calculations
      from the patient/physician perspective suggest that CT coronary angiography
      maximizes life-years respectively in 60-year-old men and women at a prior
      probability of less than 38% and 24% and maximizes QALYs at a prior probability
      of less than 17% and 11%. From the hospital/health care perspective, CT coronary
      angiography helps reduce health care and direct nonhealth care-related costs
      (according to UK/U.S. recommendations), regardless of prior probability, and
      lowers all costs, including production losses (Netherlands recommendations) at a
      prior probability of less than 87%-92%. Analysis performed from a societal
      perspective by using a willingness-to-pay threshold level of euro 80,000/QALY
      suggests that CT coronary angiography is cost-effective when the prior
      probability is lower than 44% and 37% in men and women, respectively. Sensitivity
      analyses showed that results changed across the reported range of sensitivity of
      CT coronary angiography. CONCLUSION: The optimal diagnostic work-up depends on
      the optimization criterion, prior probability of CAD, and the diagnostic
      performance of CT coronary angiography.

PMID- 19864510
TI  - Experimental design and data analysis in receiver operating characteristic
      studies: lessons learned from reports in radiology from 1997 to 2006.
AB  - PURPOSE: To provide a broad perspective concerning the recent use of receiver
      operating characteristic (ROC) analysis in medical imaging by reviewing ROC
      studies published in Radiology between 1997 and 2006 for experimental design,
      imaging modality, medical condition, and ROC paradigm. MATERIALS AND METHODS: Two
      hundred ninety-five studies were obtained by conducting a literature search with
      PubMed with two criteria: publication in Radiology between 1997 and 2006 and
      occurrence of the phrase "receiver operating characteristic." Studies returned by
      the query that were not diagnostic imaging procedure performance evaluations were
      excluded. Characteristics of the remaining studies were tabulated. RESULTS: Two
      hundred thirty-three (79.0%) of the 295 studies reported findings based on
      observers' diagnostic judgments or objective measurements. Forty-three (14.6%)
      did not include human observers, with most of these reporting an evaluation of a
      computer-aided diagnosis system or functional data obtained with computed
      tomography (CT) or magnetic resonance (MR) imaging. The remaining 19 (6.4%)
      studies were classified as reviews or meta-analyses and were excluded from our
      subsequent analysis. Among the various imaging modalities, MR imaging (46.0%) and
      CT (25.7%) were investigated most frequently. Approximately 60% (144 of 233) of
      ROC studies with human observers published in Radiology included three or fewer
      observers. CONCLUSION: ROC analysis is widely used in radiologic research,
      confirming its fundamental role in assessing diagnostic performance. However, the
      ROC studies reported in Radiology were not always adequate to support clear and
      clinically relevant conclusions.

PMID- 19864511
TI  - Breast US computer-aided diagnosis system: robustness across urban populations in
      South Korea and the United States.
AB  - PURPOSE: To evaluate the robustness of a breast ultrasonographic (US) computer
      aided diagnosis (CAD) system in terms of its performance across different patient
      populations. MATERIALS AND METHODS: Three US databases were analyzed for this
      study: one South Korean and two United States databases. All three databases were
      utilized in an institutional review board-approved and HIPAA-compliant manner.
      Round-robin analysis and independent testing were performed to evaluate the
      performance of a computerized breast cancer classification scheme across the
      databases. Receiver operating characteristic (ROC) analysis was used to evaluate
      performance differences. RESULTS: The round-robin analyses of each database
      demonstrated similar results, with areas under the ROC curve ranging from 0.88
      (95% confidence interval [CI]: 0.820, 0.918) to 0.91 (95% CI: 0.86, 0.95). The
      independent testing of each database, however, indicated that although the
      performances were similar, the range in areas under the ROC curve (from 0.79 [95%
      CI: 0.730, 0.842] to 0.87 [95% CI: 0.794, 0.923]) was wider than that with the
      round-robin tests. However, the only instances in which statistically significant
      differences in performance were demonstrated occurred when the Korean database
      was used in a testing capacity in independent testing. CONCLUSION: The few
      observed statistically significant differences in performance indicated that
      while the US features used by the system were useful across the databases, their
      relative importance differed. In practice, this means that a CAD system may need
      to be adjusted when applied to a different population.

PMID- 19864512
TI  - Impact of heart rate frequency and variability on radiation exposure, image
      quality, and diagnostic performance in dual-source spiral CT coronary
      angiography.
AB  - PURPOSE: To investigate the effect of heart rate frequency (HRF) and heart rate
      variability (HRV) on radiation exposure, image quality, and diagnostic
      performance to help detect significant stenosis (> or =50% lumen diameter
      reduction) by using adaptive electrocardiographic (ECG) pulsing at dual-source
      (DS) spiral computed tomographic (CT) coronary angiography. MATERIALS AND
      METHODS: Institutional review committee approval and informed consent were
      obtained. No prescan beta-blockers were applied. Unenhanced CT and CT coronary
      angiography with adaptive ECG pulsing were performed in 927 consecutive patients
      (600 men, 327 women; mean age, 60.3 years +/- 11.0 [standard deviation]) divided
      in three HRF groups: low, intermediate, and high (< or =65, 66-79, and > or =80
      beats/min, respectively), and four HRV groups given mean interbeat difference
      (IBD) during CT coronary angiography: normal, minor, moderate, and severe (IBDs
      of 0-1, 2-3, 4-10, and >10, respectively). Radiation exposure and image quality
      were also evaluated. In 444 of these, diagnostic performance was presented as
      sensitivity, specificity, positive predictive values (PPVs), and negative
      predictive values and likelihood ratios with corresponding 95% confidence
      intervals by using quantitative coronary angiography as the reference standard.
      RESULTS: CT coronary angiography yielded good image quality in 98% of patients
      and no significant differences in image quality were found among HRF and HRV
      groups. Radiation exposure was significantly higher in patients with low versus
      high HRF and in patients with severe versus normal HRV. No significant
      differences among HRF and HRV groups in image quality and diagnostic performance
      were found. A nonsignificant trend was found toward a lower specificity and PPV
      in patients with a high HRF or severe HRV when compared with low HRF or normal
      HRV in patients with a low calcium score (Agatston score <100). CONCLUSION: DS
      spiral CT coronary angiography performed with adaptive ECG pulsing results in
      preserved diagnostic image quality and performance independent of HRF or HRV at
      the cost of limited dose reduction in arrhythmic patients.

PMID- 19864513
TI  - Severe hyponatremia with high urine sodium and osmolality.

PMID- 19864514
TI  - Commentary.

PMID- 19864515
TI  - Commentary.

PMID- 19864520
TI  - Why do purely intraductal cancers enhance on breast MR images?

PMID- 19864521
TI  - The mea culpa conundrum.

PMID- 19864523
TI  - Recommendations for additional imaging in radiology reports: radiologists' self
      referral or good clinical practice?

PMID- 19864524
TI  - National Council on Radiation Protection and Measurements report shows
      substantial medical exposure increase.

PMID- 19864525
TI  - Soft-tissue tumors and tumorlike lesions: a systematic imaging approach.
AB  - Soft-tissue lesions are frequently encountered by radiologists in everyday
      clinical practice. Characterization of these soft-tissue lesions remains
      problematic, despite advances in imaging. By systematically using clinical
      history, lesion location, mineralization on radiographs, and signal intensity
      characteristics on magnetic resonance images, one can (a) determine the diagnosis
      for the subset of determinate lesions that have characteristic clinical and
      imaging features and (b) narrow the differential diagnosis for lesions that
      demonstrate indeterminate characteristics. If a lesion cannot be characterized as
      a benign entity, the lesion should be reported as indeterminate, and the patient
      should undergo biopsy to exclude malignancy.

PMID- 19864526
TI  - CT of coronary artery disease.
AB  - Technical innovation is rapidly improving the clinical utility of cardiac
      computed tomography (CT) and will increasingly address current technical
      limitations, especially the association of this test with relatively high levels
      of radiation. Guidelines for appropriate indications are in place and are
      evolving, with an increasing evidence base to ensure the appropriate use of this
      modality. New technologies and new applications, such as myocardial perfusion
      imaging and dual-energy CT, are being explored and are widening the scope of
      coronary CT angiography from mere coronary artery assessment to the integrative
      analysis of cardiac morphology, function, perfusion, and viability. The
      scientific evaluation of coronary CT angiography has left the stage of
      feasibility testing and increasingly, evidence-based data are accumulating on
      outcomes, prognosis, and cost-effectiveness. In this review, these developments
      will be discussed in the context of current pivotal transitions in cardiovascular
      disease management and their potential influence on the current role and future
      fate of coronary CT angiography will be examined.

PMID- 19864527
TI  - Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast
      enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in
      a murine model.
AB  - PURPOSE: To combine dynamic contrast material-enhanced (DCE) magnetic resonance
      (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue
      samples from mice to identify the spatial distribution of gadolinium after
      intravenous injection. MATERIALS AND METHODS: C3(1) Sv-40 large T antigen
      transgenic mice (n = 23) were studied with institutional animal care and use
      committee approval. Twelve mice underwent DCE MR imaging after injection of
      gadodiamide, and gadolinium concentration-time curves were fit to a two
      compartment pharmacokinetic model with the following parameters: transfer
      constant (K(trans)) and volume of extravascular extracellular space per unit
      volume of tissue (v(e)). Eleven mice received gadodiamide before XFM. These mice
      were sacrificed 2 minutes after injection, and frozen slices containing ducts
      distended with murine ductal carcinoma in situ (DCIS) were prepared for XFM. One
      mouse received saline and served as the control animal. Elemental gadolinium
      concentrations were measured in and around the ducts with DCIS. Hematoxylin-eosin
      stained slices of mammary tissues were obtained after DCE MR imaging and XFM.
      RESULTS: Ducts containing DCIS were unambiguously identified on MR images. DCE MR
      imaging revealed gadolinium uptake along the length of ducts with DCIS, with an
      average K(trans) of 0.21 min(-1) +/- 0.14 (standard deviation) and an average
      v(e) of 0.40 +/- 0.16. XFM revealed gadolinium uptake inside ducts with DCIS,
      with an average concentration of 0.475 mmol/L +/- 0.380; the corresponding value
      for DCE MR imaging was 0.30 mmol/L +/- 0.13. CONCLUSION: These results provide
      insight into the physiologic basis of contrast enhancement of DCIS lesions on DCE
      MR images: Gadolinium penetrates and collects inside neoplastic ducts.

PMID- 19864528
TI  - CT enteroclysis features of uncomplicated celiac disease: retrospective analysis
      of 44 patients.
AB  - PURPOSE: To describe the computed tomographic (CT) enteroclysis features of
      uncomplicated celiac disease (CD) and to determine the most indicative appearance
      of this condition by using a retrospective case-control study. MATERIALS AND
      METHODS: This study had institutional review board approval. The CT enteroclysis
      examinations of 44 consecutive patients with proved uncomplicated CD (21 men, 23
      women; mean age, 44.45 years) were reviewed by two blinded readers and compared
      with those obtained in 44 control subjects (21 men, 23 women; mean age, 44.48
      years), who were matched for sex and age. Comparisons were calculated by using
      univariate analysis. RESULTS: Reversed jejunoileal fold pattern had the highest
      specificity (100%; 44 of 44; 95% confidence interval [CI]: 91.96%, 100%) and was
      the most discriminating independent variable for the diagnosis of uncomplicated
      CD (odds ratio, 39.9; P < .0001) but had a sensitivity of 63.64% (28 of 44; 95%
      CI: 47.77%, 77.59%). Ileal fold thickening, vascular engorgement, and splenic
      atrophy were other variables that strongly correlated with the presence of
      uncomplicated CD. CONCLUSION: CT enteroclysis may help establish a diagnosis of
      uncomplicated CD and may clarify the cause of nonspecific gastrointestinal
      symptoms in patients with unknown CD. However, future prospective trials are
      needed to determine the actual value of CT enteroclysis in patients with CD and
      validate the clinical usefulness of CT enteroclysis in the detection of unknown
      uncomplicated CD.

PMID- 19864531
TI  - Case 151: hereditary angioedema in the duodenum.

PMID- 19864529
TI  - Clinical stage T1c prostate cancer: evaluation with endorectal MR imaging and MR
      spectroscopic imaging.
AB  - PURPOSE: To assess the diagnostic accuracy of endorectal magnetic resonance (MR)
      imaging and MR spectroscopic imaging for prediction of the pathologic stage of
      prostate cancer and the presence of clinically nonimportant disease in patients
      with clinical stage T1c prostate cancer. MATERIALS AND METHODS: The institutional
      review board approved-and waived the informed patient consent requirement for
      this HIPAA-compliant study involving 158 patients (median age, 58 years; age
      range, 40-76 years) who had clinical stage T1c prostate cancer, had not been
      treated preoperatively, and underwent combined 1.5-T endorectal MR imaging-MR
      spectroscopic imaging between January 2003 and March 2004 before undergoing
      radical prostatectomy. On the MR images and combined endorectal MR-MR
      spectroscopic images, two radiologists retrospectively and independently rated
      the likelihood of cancer in 12 prostate regions and the likelihoods of
      extracapsular extension (ECE), seminal vesicle invasion (SVI), and adjacent organ
      invasion by using a five-point scale, and they determined the probability of
      clinically nonimportant prostate cancer by using a four-point scale. Whole-mount
      step-section pathology maps were used for imaging-pathologic analysis
      correlation. Receiver operating characteristic curves were constructed and areas
      under the curves (AUCs) were estimated nonparametrically for assessment of reader
      accuracy. RESULTS: At surgical-pathologic analysis, one (0.6%) patient had no
      cancer; 124 (78%) patients, organ-confined (stage pT2) disease; 29 (18%)
      patients, ECE (stage pT3a); two (1%) patients, SVI (stage pT3b); and two (1%)
      patients, bladder neck invasion (stage pT4). Forty-six (29%) patients had a total
      tumor volume of less than 0.5 cm(3). With combined MR imaging-MR spectroscopic
      imaging, the two readers achieved 80% accuracy in disease staging and AUCs of
      0.62 and 0.71 for the prediction of clinically nonimportant cancer. CONCLUSION:
      Clinical stage T1c prostate cancers are heterogeneous in pathologic stage and
      volume. MR imaging may help to stratify patients with clinical stage T1c disease
      for appropriate clinical management.

PMID- 19864532
TI  - Barking up the wrong straw man.

PMID- 19864533
TI  - The need for spatially standardized methods in clinical applications of diffusion
      tensor imaging of white matter.

PMID- 19864534
TI  - Epinephrine dose for treating contrast material-induced reactions.

PMID- 19864535
TI  - Falsely claiming use of NASCET percentage stenosis method.

PMID- 19864536
TI  - Result categories for ventilation-perfusion scintigraphy.

PMID- 19864537
TI  - Furthering our understanding of pathogen transmission in cystic fibrosis.

PMID- 19864538
TI  - Medication adherence in COPD: what have we learned?

PMID- 19864539
TI  - Airways disease: just nosing around?

PMID- 19864543
TI  - Upper airway x 1: allergic rhinitis and asthma: united disease through epithelial
      cells.
AB  - The relationship between allergic rhinitis and asthma is now established, and
      most of the clinical, epidemiological and biological data recommend integrated
      management. Epithelial cells represent the first barrier of the upper and lower
      respiratory tracts and thus are logical targets for a comprehensive integrated
      therapeutic approach. This review discusses rhinosinusitis as a co-morbid
      condition, a precipitating or triggering condition, and an epiphenomenon as an
      integrated part of the disease. A better understanding and a more pragmatic
      method of diagnosis and management is needed using cost-effective long-term
      strategies.

PMID- 19864545
TI  - Longitudinal changes in gastro-oesophageal reflux from 3 months to 6 months after
      lung transplantation.

PMID- 19864546
TI  - Thoracic ultrasound in malignant pleural effusion: a real world perspective.

PMID- 19864547
TI  - Merkel cell polyomavirus is prevalent in a subset of small cell lung cancer: a
      study of 31 patients.

PMID- 19864548
TI  - Attitudes of patients towards a hospital-based rehabilitation service for obesity
      hypoventilation syndrome.

PMID- 19864549
TI  - Assessment of gender differences in health status with the Leicester Cough
      Questionnaire (LCQ).

PMID- 19864550
TI  - Are patients on treatment for pulmonary TB who stop expectorating sputum
      genuinely culture negative?

PMID- 19864551
TI  - Airway epithelial cells as guardians of immune homeostasis?

PMID- 19864552
TI  - A suspicious clot.

PMID- 19864553
TI  - Dual energy CT pulmonary angiography: findings in a patient with chronic
      thromboembolic pulmonary hypertension.

PMID- 19864554
TI  - Are the boundary-related cells in the subiculum boundary-vector cells?

PMID- 19864555
TI  - Prelimbic prefrontal neurons drive fear expression: a clue for extinction-
      reconsolidation interactions.

PMID- 19864557
TI  - Dual neural routing of visual facilitation in speech processing.
AB  - Viewing our interlocutor facilitates speech perception, unlike for instance when
      we telephone. Several neural routes and mechanisms could account for this
      phenomenon. Using magnetoencephalography, we show that when seeing the
      interlocutor, latencies of auditory responses (M100) are the shorter the more
      predictable speech is from visual input, whether the auditory signal was
      congruent or not. Incongruence of auditory and visual input affected auditory
      responses approximately 20 ms after latency shortening was detected, indicating
      that initial content-dependent auditory facilitation by vision is followed by a
      feedback signal that reflects the error between expected and received auditory
      input (prediction error). We then used functional magnetic resonance imaging and
      confirmed that distinct routes of visual information to auditory processing
      underlie these two functional mechanisms. Functional connectivity between visual
      motion and auditory areas depended on the degree of visual predictability,
      whereas connectivity between the superior temporal sulcus and both auditory and
      visual motion areas was driven by audiovisual (AV) incongruence. These results
      establish two distinct mechanisms by which the brain uses potentially predictive
      visual information to improve auditory perception. A fast direct corticocortical
      pathway conveys visual motion parameters to auditory cortex, and a slower and
      indirect feedback pathway signals the error between visual prediction and
      auditory input.

PMID- 19864556
TI  - Identification of two distinct macrophage subsets with divergent effects causing
      either neurotoxicity or regeneration in the injured mouse spinal cord.
AB  - Macrophages dominate sites of CNS injury in which they promote both injury and
      repair. These divergent effects may be caused by distinct macrophage subsets,
      i.e., "classically activated" proinflammatory (M1) or "alternatively activated"
      anti-inflammatory (M2) cells. Here, we show that an M1 macrophage response is
      rapidly induced and then maintained at sites of traumatic spinal cord injury and
      that this response overwhelms a comparatively smaller and transient M2 macrophage
      response. The high M1/M2 macrophage ratio has significant implications for CNS
      repair. Indeed, we present novel data showing that only M1 macrophages are
      neurotoxic and M2 macrophages promote a regenerative growth response in adult
      sensory axons, even in the context of inhibitory substrates that dominate sites
      of CNS injury (e.g., proteoglycans and myelin). Together, these data suggest that
      polarizing the differentiation of resident microglia and infiltrating blood
      monocytes toward an M2 or "alternatively" activated macrophage phenotype could
      promote CNS repair while limiting secondary inflammatory-mediated injury.

PMID- 19864558
TI  - Control of on/off glomerular signaling by a local GABAergic microcircuit in the
      olfactory bulb.
AB  - Odors are coded at the input level of the olfactory bulb by a spatial map of
      activated glomeruli, reflecting different odorant receptors (ORs) stimulated in
      the nose. Here we examined the function of local synaptic processing within
      glomeruli in transforming these input patterns into an output for the bulb, using
      patch-clamp recordings and calcium imaging in rat bulb slices. Two types of
      transformations were observed at glomeruli, the first of which produced a
      bimodal, "on/off" glomerular signal that varied probabilistically depending on
      olfactory receptor neuron (ORN) input levels. The bimodal response behavior was
      seen in glomerular synaptic responses, as well as in action potential ("spike")
      firing, wherein all mitral cells affiliated with a glomerulus either engaged in
      prolonged spike bursts or did not spike at all. In addition, evidence was
      obtained that GABAergic periglomerular (PG) cells that surround a glomerulus can
      prevent activation of a glomerulus through inhibitory inputs targeted onto
      excitatory external tufted cells. The path of PG cell activation appeared to be
      confined to one glomerulus, such that ORNs at one glomerulus initiated inhibition
      of the same glomerulus. The observed glomerular "self-inhibition" provides a
      mechanism of filtering odor signals that would be an alternative to commonly
      proposed mechanisms of lateral inhibition between OR-specific glomeruli. In this
      case, selective suppression of weak odor signals could be achieved based on the
      difference in the input resistance of PG cells versus excitatory neurons at a
      glomerulus.

PMID- 19864559
TI  - Brain hemispheres selectively track the expected value of contralateral options.
AB  - A main focus in economics is on binary choice situations, in which human agents
      have to choose between two alternative options. The classical view is that
      decision making consists of valuating each option, comparing the two expected
      values, and selecting the higher one. Some neural correlates of option values
      have been described in animals, but little is known about how they are
      represented in the human brain: are they integrated into a single center or
      distributed over different areas? To address this issue, we examined whether the
      expected values of two options, which were cued by visual symbols and chosen with
      either the left or right hand, could be distinguished using functional magnetic
      resonance imaging. The two options were linked to monetary rewards through
      probabilistic contingencies that subjects had to learn so as to maximize payoff.
      Learning curves were fitted with a standard computational model that updates, on
      a trial-by-trial basis, the value of the chosen option in proportion to a reward
      prediction error. Results show that during learning, left and right option values
      were specifically expressed in the contralateral ventral prefrontal cortex,
      regardless of the upcoming choice. We therefore suggest that expected values are
      represented in a distributed manner that respects the topography of the brain
      systems elicited by the available options.

PMID- 19864560
TI  - A key role for gp130 expressed on peripheral sensory nerves in pathological pain.
AB  - Interleukin-6 (IL-6) is a key mediator of inflammation. Inhibitors of IL-6 or of
      its signal transducing receptor gp130 constitute a novel class of anti
      inflammatory drugs, which raise great hopes for improved treatments of painful
      inflammatory diseases such as rheumatoid arthritis. IL-6 and gp130 may enhance
      pain not only indirectly through their proinflammatory actions but also through a
      direct action on nociceptors (i.e., on neurons activated by painful stimuli). We
      found indeed that the IL-6/gp130 ligand-receptor complex induced heat
      hypersensitivity both in vitro and in vivo. This process was mediated by
      activation of PKC-delta via Gab1/2/PI(3)K and subsequent regulation of TRPV1, a
      member of the transient receptor potential (TRP) family of ion channels. To
      assess the relevance of this direct pain promoting effect of IL-6, we generated
      conditional knock-out mice, which lack gp130 specifically in nociceptors, and
      tested them in models of inflammatory and tumor-induced pain. These mice showed
      significantly reduced levels of inflammatory and tumor-induced pain but no
      changes in immune reactions or tumor growth. Our results uncover the significance
      of gp130 expressed in peripheral pain sensing neurons in the pathophysiology of
      major clinical pain disorders and suggest their use as novel pain relieving
      agents in inflammatory and tumor pain.

PMID- 19864561
TI  - Oscillations, phase-of-firing coding, and spike timing-dependent plasticity: an
      efficient learning scheme.
AB  - Recent experiments have established that information can be encoded in the spike
      times of neurons relative to the phase of a background oscillation in the local
      field potential-a phenomenon referred to as "phase-of-firing coding" (PoFC).
      These firing phase preferences could result from combining an oscillation in the
      input current with a stimulus-dependent static component that would produce the
      variations in preferred phase, but it remains unclear whether these phases are an
      epiphenomenon or really affect neuronal interactions-only then could they have a
      functional role. Here we show that PoFC has a major impact on downstream learning
      and decoding with the now well established spike timing-dependent plasticity
      (STDP). To be precise, we demonstrate with simulations how a single neuron
      equipped with STDP robustly detects a pattern of input currents automatically
      encoded in the phases of a subset of its afferents, and repeating at random
      intervals. Remarkably, learning is possible even when only a small fraction of
      the afferents ( approximately 10%) exhibits PoFC. The ability of STDP to detect
      repeating patterns had been noted before in continuous activity, but it turns out
      that oscillations greatly facilitate learning. A benchmark with more conventional
      rate-based codes demonstrates the superiority of oscillations and PoFC for both
      STDP-based learning and the speed of decoding: the oscillation partially formats
      the input spike times, so that they mainly depend on the current input currents,
      and can be efficiently learned by STDP and then recognized in just one
      oscillation cycle. This suggests a major functional role for oscillatory brain
      activity that has been widely reported experimentally.

PMID- 19864562
TI  - Endogenous BDNF in the dorsolateral striatum gates alcohol drinking.
AB  - We previously found that brain-derived neurotrophic factor (BDNF)-haplodeficient
      mice exhibit greater ethanol-induced place preference and psychomotor
      sensitization, and greater ethanol consumption after deprivation, than control
      mice. We further observed that, in mice, voluntary ethanol intake increases BDNF
      expression in the dorsal striatum (DS). Here, we determined whether BDNF within
      the DS regulates ethanol self-administration in Long-Evans rats trained to self
      administer a 10% ethanol solution. We observed a greater increase in BDNF
      expression after ethanol self-administration in the dorsolateral striatum (DLS)
      than in the dorsomedial striatum (DMS). We further found that downregulation of
      endogenous BDNF using viral-mediated siRNA in the DLS, but not in the DMS,
      significantly increased ethanol self-administration. Infusion of exogenous BDNF
      (0.25 microg/microl/side into the DMS; 0.25 and 0.75 microg/microl/side into the
      DLS) attenuated responding for ethanol when infused 3 h before the beginning of
      the self-administration session. Although the decrease in ethanol intake was
      similar in the DLS and DMS, BDNF infused in the DLS, but not in the DMS, induced
      an early termination of the drinking episode. Furthermore, the action of BDNF in
      the DLS was specific for ethanol, as infusion of the neurotrophic factor in the
      DMS, but not DLS, resulted in a reduction of sucrose intake. Together, these
      findings demonstrate that the BDNF pathway within the DLS controls the level of
      ethanol self-administration. Importantly, our results suggest that an endogenous
      signaling pathway within the same brain region that mediates drug-taking behavior
      also plays a critical role in gating the level of ethanol intake.

PMID- 19864563
TI  - Classical major histocompatibility complex class I molecules in motoneurons: new
      actors at the neuromuscular junction.
AB  - Major histocompatibility complex (MHC) class I molecules have fundamental
      functions in the immune system. Recent studies have suggested that these
      molecules may also have non-immune functions in the nervous system, in particular
      related to synaptic function and plasticity. Because adult motoneurons express
      mRNAs for MHC class I molecules, we have examined their subcellular expression
      pattern in vivo and their role for the synaptic connectivity of these neurons. We
      observed immunoreactivity for classical MHC class I (Ia) protein in motoneuron
      somata, but the predominant expression was found in axons and presynaptically at
      neuromuscular junctions (NMJs). Peripheral nerve lesion induced a strong increase
      of motoneuron MHC class Ia (H2-K(b)/D(b)) mRNA, indicating a role for MHC class
      Ia molecules during regeneration. Accordingly, there was an accumulation of MHC
      class Ia proteins at the cut ends and in growth cones of motor axons after
      lesion. In K(b-/-)D(b-/-) mice (lacking MHC class Ia molecules), the time course
      for recovery of grip ability in reinnervated muscles was significantly delayed.
      Muscles from K(b-/-)D(b-/-) mice displayed an increased density and a disturbed
      distribution of NMJs and fewer terminal Schwann cells/NMJ compared with wild-type
      mice. A population of Schwann cells in sciatic nerves expressed the paired Ig
      receptor B, which binds to MHC class I molecules. These results provide the first
      evidence that neuronal MHC class Ia molecules are present in motor axons, that
      they are important for organization of NMJs and motor recovery after nerve
      lesion, and that their actions may be mediated via Schwann cells.

PMID- 19864564
TI  - Predicting language lateralization from gray matter.
AB  - It has long been predicted that the degree to which language is lateralized to
      the left or right hemisphere might be reflected in the underlying brain anatomy.
      We investigated this relationship on a voxel-by-voxel basis across the whole
      brain using structural and functional magnetic resonance images from 86 healthy
      participants. Structural images were converted to gray matter probability images,
      and language activation was assessed during naming and semantic decision. All
      images were spatially normalized to the same symmetrical template, and
      lateralization images were generated by subtracting right from left hemisphere
      signal at each voxel. We show that the degree to which language was left or right
      lateralized was positively correlated with the degree to which gray matter
      density was lateralized. Post hoc analyses revealed a general relationship
      between gray matter probability and blood oxygenation level-dependent signal.
      This is the first demonstration that structural brain scans can be used to
      predict language lateralization on a voxel-by-voxel basis in the normal healthy
      brain.

PMID- 19864565
TI  - Human reinforcement learning subdivides structured action spaces by learning
      effector-specific values.
AB  - Humans and animals are endowed with a large number of effectors. Although this
      enables great behavioral flexibility, it presents an equally formidable
      reinforcement learning problem of discovering which actions are most valuable
      because of the high dimensionality of the action space. An unresolved question is
      how neural systems for reinforcement learning-such as prediction error signals
      for action valuation associated with dopamine and the striatum-can cope with this
      "curse of dimensionality." We propose a reinforcement learning framework that
      allows for learned action valuations to be decomposed into effector-specific
      components when appropriate to a task, and test it by studying to what extent
      human behavior and blood oxygen level-dependent (BOLD) activity can exploit such
      a decomposition in a multieffector choice task. Subjects made simultaneous
      decisions with their left and right hands and received separate reward feedback
      for each hand movement. We found that choice behavior was better described by a
      learning model that decomposed the values of bimanual movements into separate
      values for each effector, rather than a traditional model that treated the
      bimanual actions as unitary with a single value. A decomposition of value into
      effector-specific components was also observed in value-related BOLD signaling,
      in the form of lateralized biases in striatal correlates of prediction error and
      anticipatory value correlates in the intraparietal sulcus. These results suggest
      that the human brain can use decomposed value representations to "divide and
      conquer" reinforcement learning over high-dimensional action spaces.

PMID- 19864566
TI  - Adult-born hippocampal dentate granule cells undergoing maturation modulate
      learning and memory in the brain.
AB  - Adult-born dentate granule cells (DGCs) contribute to learning and memory, yet it
      remains unknown when adult-born DGCs become involved in the cognitive processes.
      During neurogenesis, immature DGCs display distinctive physiological
      characteristics while undergoing morphological maturation before final
      integration into the neural circuits. The survival and activity of the adult-born
      DGCs can be influenced by the experience of the animal during a critical period
      when newborn DGCs are still immature. To assess the temporal importance of adult
      neurogenesis, we developed a transgenic mouse model that allowed us to
      transiently reduce the numbers of adult-born DGCs in a temporally regulatable
      manner. We found that mice with a reduced population of adult-born DGCs at the
      immature stage were deficient in forming robust, long-term spatial memory and
      displayed impaired performance in extinction tasks. These results suggest that
      immature DGCs that undergo maturation make important contributions to learning
      and memory.

PMID- 19864567
TI  - Simvastatin inhibits the activation of p21ras and prevents the loss of
      dopaminergic neurons in a mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is second only to Alzheimer's disease as the most common
      devastating human neurodegenerative disorder. Despite intense investigation, no
      interdictive therapy is available for PD. We investigated whether simvastatin, a
      Food and Drug Administration-approved cholesterol-lowering drug, could protect
      against nigrostriatal degeneration after 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) intoxication to model PD in mice. First, MPP(+) induced
      the activation of p21(ras) and nuclear factor-kappaB (NF-kappaB) in mouse
      microglial cells. Inhibition of MPP(+)-induced activation of NF-kappaB by
      Deltap21(ras), a dominant-negative mutant of p21(ras), supported the involvement
      of p21(ras) in MPP(+)-induced microglial activation of NF-kappaB. Interestingly,
      simvastatin attenuated activation of both p21(ras) and NF-kappaB in MPP(+)
      stimulated microglial cells. Consistently, we found a very rapid activation of
      p21(ras) in vivo in the substantia nigra pars compacta of MPTP-intoxicated mice.
      However, after oral administration, simvastatin entered into the nigra, reduced
      nigral activation of p21(ras), attenuated nigral activation of NF-kappaB,
      inhibited nigral expression of proinflammatory molecules, and suppressed nigral
      activation of glial cells. These findings paralleled dopaminergic neuronal
      protection, normalized striatal neurotransmitters, and improved motor functions
      in MPTP-intoxicated mice. Similarly, pravastatin, another cholesterol-lowering
      drug, suppressed microglial inflammatory responses and protected dopaminergic
      neurons in MPTP-intoxicated mice, but at levels less than simvastatin.
      Furthermore, both the statins administered 2 d after initiation of the disease
      were still capable of inhibiting the demise of dopaminergic neurons and
      concomitant loss of neurotransmitters, suggesting that statins are capable of
      slowing down the progression of neuronal loss in the MPTP mouse model. Therefore,
      we conclude that statins may be of therapeutic benefit for PD patients.

PMID- 19864568
TI  - Structural changes between seasons in the songbird auditory forebrain.
AB  - The song control system (SCS) of seasonal songbirds shows remarkable seasonal
      plasticity. Male starlings (Sturnus vulgaris) sing throughout the year, but in
      the breeding season, when concentrations of testosterone are elevated, the song
      is highly sexually motivated. The main goal of this study was to investigate
      structural seasonal changes in regions involved in auditory processing and in
      socio-sexual behavior. Using in vivo Diffusion Tensor Imaging (DTI), we measured
      in breeding and nonbreeding seasons volume and tissue characteristics of several
      brain regions of nine adult male starlings. We demonstrate that the songbird
      brain exhibits an extreme seasonal plasticity not merely limited to the SCS.
      Volumetric analysis showed seasonal telencephalon volume changes and more
      importantly also a volumetric change in the caudal region of the nidopallium
      (NCM), a region analogous to the mammalian secondary auditory cortex. Analysis of
      the DTI data allowed detection of seasonal changes in cellular attributes in NCM
      and regions involved in social behavior. This study extends our view on a
      seasonally dynamic avian brain which not only hones its song control system but
      also auditory and social systems to be prepared for the breeding season.

PMID- 19864569
TI  - Spinal interneurons differentiate sequentially from those driving the fastest
      swimming movements in larval zebrafish to those driving the slowest ones.
AB  - Studies of neuronal networks have revealed few general principles that link
      patterns of development with later functional roles. While investigating the
      neural control of movements, we recently discovered a topographic map in the
      spinal cord of larval zebrafish that relates the position of motoneurons and
      interneurons to their order of recruitment during swimming. Here, we show that
      the map reflects an orderly pattern of differentiation of neurons driving
      different movements. First, we use high-speed filming to show that large
      amplitude swimming movements with bending along much of the body appear first,
      with smaller, regional swimming movements emerging later. Next, using whole-cell
      patch recordings, we demonstrate that the excitatory circuits that drive large
      amplitude, fast swimming movements at larval stages are present and functional
      early on in embryos. Finally, we systematically assess the orderly emergence of
      spinal circuits according to swimming speed using transgenic fish expressing the
      photoconvertible protein Kaede to track neuronal differentiation in vivo. We
      conclude that a simple principle governs the development of spinal networks in
      which the neurons driving the fastest, most powerful swimming in larvae develop
      first with ones that drive increasingly weaker and slower larval movements
      layered on over time. Because the neurons are arranged by time of differentiation
      in the spinal cord, the result is a topographic map that represents the
      speed/strength of movements at which neurons are recruited and the temporal
      emergence of networks. This pattern may represent a general feature of neuronal
      network development throughout the brain and spinal cord.

PMID- 19864570
TI  - Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative
      pathology in alpha-synuclein models of Parkinson's and Lewy body diseases.
AB  - Accumulation of the synaptic protein alpha-synuclein (alpha-syn) is a hallmark of
      Parkinson's disease (PD) and Lewy body disease (LBD), a heterogeneous group of
      disorders with dementia and parkinsonism, where Alzheimer's disease and PD
      interact. Accumulation of alpha-syn in these patients might be associated with
      alterations in the autophagy pathway. Therefore, we postulate that delivery of
      beclin 1, a regulator of the autophagy pathway, might constitute a strategy
      toward developing a therapy for LBD/PD. Overexpression of alpha-syn from
      lentivirus transduction in a neuronal cell line resulted in lysosomal
      accumulation and alterations in autophagy. Coexpression of beclin 1 activated
      autophagy, reduced accumulation of alpha-syn, and ameliorated associated neuritic
      alterations. The effects of beclin 1 overexpression on LC3 and alpha-syn
      accumulation were partially blocked by 3-MA and completely blocked by bafilomycin
      A1. In contrast, rapamycin enhanced the effects of beclin 1. To evaluate the
      potential effects of activating autophagy in vivo, a lentivirus expressing beclin
      1 was delivered to the brain of a alpha-syn transgenic mouse. Neuropathological
      analysis demonstrated that beclin 1 injections ameliorated the synaptic and
      dendritic pathology in the tg mice and reduced the accumulation of alpha-syn in
      the limbic system without any significant deleterious effects. This was
      accompanied by enhanced lysosomal activation and reduced alterations in the
      autophagy pathway. Thus, beclin 1 plays an important role in the intracellular
      degradation of alpha-syn either directly or indirectly through the autophagy
      pathway and may present a novel therapeutic target for LBD/PD.

PMID- 19864571
TI  - Intrabody gene therapy ameliorates motor, cognitive, and neuropathological
      symptoms in multiple mouse models of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      resulting from the expansion of a glutamine repeat in the huntingtin (Htt)
      protein. Current therapies are directed at managing symptoms such as chorea and
      psychiatric disturbances. In an effort to develop a therapy directed at disease
      prevention we investigated the utility of highly specific, anti-Htt intracellular
      antibodies (intrabodies). We previously showed that V(L)12.3, an intrabody
      recognizing the N terminus of Htt, and Happ1, an intrabody recognizing the
      proline-rich domain of Htt, both reduce mHtt-induced toxicity and aggregation in
      cell culture and brain slice models of HD. Due to the different mechanisms of
      action of these two intrabodies, we then tested both in the brains of five mouse
      models of HD using a chimeric adeno-associated virus 2/1 (AAV2/1) vector with a
      modified CMV enhancer/chicken beta-actin promoter. V(L)12.3 treatment, while
      beneficial in a lentiviral model of HD, has no effect on the YAC128 HD model and
      actually increases severity of phenotype and mortality in the R6/2 HD model. In
      contrast, Happ1 treatment confers significant beneficial effects in a variety of
      assays of motor and cognitive deficits. Happ1 also strongly ameliorates the
      neuropathology found in the lentiviral, R6/2, N171-82Q, YAC128, and BACHD models
      of HD. Moreover, Happ1 significantly prolongs the life span of N171-82Q mice.
      These results indicate that increasing the turnover of mHtt using AAV-Happ1 gene
      therapy represents a highly specific and effective treatment in diverse mouse
      models of HD.

PMID- 19864572
TI  - Molecular reconstruction of mGluR5a-mediated endocannabinoid signaling cascade in
      single rat sympathetic neurons.
AB  - Endocannabinoids (eCB) such as 2-arachidonylglycerol (2-AG) are lipid metabolites
      that are synthesized in a postsynaptic neurons and act upon CB(1) cannabinoid
      receptors (CB(1)R) in presynaptic nerve terminals. This retrograde transmission
      underlies several forms of short and long term synaptic plasticity within the
      CNS. Here, we constructed a model system based on isolated rat sympathetic
      neurons, in which an eCB signaling cascade could be studied in a reduced,
      spatially compact, and genetically malleable system. We constructed a complete
      eCB production/mobilization pathway by sequential addition of molecular
      components. Heterologous expression of four components was required for eCB
      production and detection: metabotropic glutamate receptor 5a (mGluR5a), Homer 2b,
      diacylglycerol lipase alpha, and CB(1)R. In these neurons, application of l
      glutamate produced voltage-dependent modulation of N-type Ca(2+) channels
      mediated by activation of CB(1)R. Using both molecular dissection and
      pharmacological agents, we provide evidence that activation of mGluR5a results in
      rapid enzymatic production of 2-AG followed by activation of CB(1)R. These
      experiments define the critical elements required to recapitulate retrograde eCB
      production and signaling in a single peripheral neuron. Moreover,
      production/mobilization of eCB can be detected on a physiologically relevant time
      scale using electrophysiological techniques. The system provides a platform for
      testing candidate molecules underlying facilitation of eCB transport across the
      plasma membrane.

PMID- 19864573
TI  - Broadband shifts in local field potential power spectra are correlated with
      single-neuron spiking in humans.
AB  - A fundamental question in neuroscience concerns the relation between the spiking
      of individual neurons and the aggregate electrical activity of neuronal ensembles
      as seen in local field potentials (LFPs). Because LFPs reflect both spiking
      activity and subthreshold events, this question is not simply one of data
      aggregation. Recording from 20 neurosurgical patients, we directly examined the
      relation between LFPs and neuronal spiking. Examining 2030 neurons in widespread
      brain regions, we found that firing rates were positively correlated with
      broadband (2-150 Hz) shifts in the LFP power spectrum. In contrast, narrowband
      oscillations correlated both positively and negatively with firing rates at
      different recording sites. Broadband power shifts were a more reliable predictor
      of neuronal spiking than narrowband power shifts. These findings suggest that
      broadband LFP power provides valuable information concerning neuronal activity
      beyond that contained in narrowband oscillations.

PMID- 19864574
TI  - Perceptual learning of object shape.
AB  - Recognition of objects is accomplished through the use of cues that depend on
      internal representations of familiar shapes. We used a paradigm of perceptual
      learning during visual search to explore what features human observers use to
      identify objects. Human subjects were trained to search for a target object
      embedded in an array of distractors, until their performance improved from near
      chance levels to over 80% of trials in an object-specific manner. We determined
      the role of specific object components in the recognition of the object as a
      whole by measuring the transfer of learning from the trained object to other
      objects sharing components with it. Depending on the geometric relationship of
      the trained object with untrained objects, transfer to untrained objects was
      observed. Novel objects that shared a component with the trained object were
      identified at much higher levels than those that did not, and this could be used
      as an indicator of which features of the object were important for recognition.
      Training on an object also transferred to the components of the object when these
      components were embedded in an array of distractors of similar complexity. These
      results suggest that objects are not represented in a holistic manner during
      learning but that their individual components are encoded. Transfer between
      objects was not complete and occurred for more than one component, regardless of
      how well they distinguish the object from distractors. This suggests that a joint
      involvement of multiple components was necessary for full performance.

PMID- 19864575
TI  - Cytoplasmic polyadenylation element-binding protein regulates neurotrophin-3
      dependent beta-catenin mRNA translation in developing hippocampal neurons.
AB  - Neuronal morphogenesis, the growth and arborization of neuronal processes, is an
      essential component of brain development. Two important but seemingly disparate
      components regulating neuronal morphology have previously been described. In the
      hippocampus, neurotrophins, particularly brain-derived neurotrophic factor (BDNF)
      and neurotrophin-3 (NT3), act to enhance cell growth and branching, while
      activity-induced branching was shown to be dependent upon intracellular beta
      catenin. We now describe a molecular link between NT3 stimulation and beta
      catenin increase in developing neurons and demonstrate that this process is
      required for the NT3-mediated increase in process branching. Here, we show that
      beta-catenin is rapidly increased specifically in growth cones following NT3
      stimulation. This increase in beta-catenin is protein synthesis dependent and
      requires the activity of cytoplasmic polyadenylation element-binding protein-1
      (CPEB1), an mRNA-binding protein that regulates mRNA translation. We find that
      CPEB1 protein binds beta-catenin mRNA in a CPE-dependent manner and that both
      localize to growth cones of developing hippocampal neurons. Both the NT3-mediated
      rapid increase in beta-catenin and process branching are abolished when CPEB1
      function is inhibited. In addition, the NT3-mediated increase in beta-catenin in
      growth cones is dependent upon internal calcium and the activity of CaMKII
      (calcium/calmodulin-dependent kinase II). Together, these results suggest that
      CPEB1 regulates beta-catenin synthesis in neurons and may contribute to neuronal
      morphogenesis.

PMID- 19864577
TI  - Dendritic compartment and neuronal output mode determine pathway-specific long
      term potentiation in the piriform cortex.
AB  - The apical dendrite of layer 2/3 pyramidal cells in the piriform cortex receives
      two spatially distinct inputs: one projecting onto the distal apical dendrite in
      sensory layer 1a, the other targeting the proximal apical dendrite in layer 1b.
      We observe an expression gradient of A-type K(+) channels that weakens the
      backpropagating action potential-mediated depolarization in layer 1a compared
      with layer 1b. We find that the pairing of presynaptic and postsynaptic firing
      leads to significantly smaller Ca(2+) signals in the distal dendritic spines in
      layer 1a compared with the proximal spines in layer 1b. The consequence is a
      selective failure to induce long-term potentiation (LTP) in layer 1a, which can
      be rescued by pharmacological enhancement of action potential backpropagation. In
      contrast, LTP induction by pairing presynaptic and postsynaptic firing is
      possible in layer 1b but requires bursting of the postsynaptic cell. This output
      mode strongly depends on the balance of excitation and inhibition in the piriform
      cortex. We show, on the single-spine level, how the plasticity of functionally
      distinct synapses is gated by the intrinsic electrical properties of piriform
      cortex layer 2 pyramidal cell dendrites and the cellular output mode.

PMID- 19864576
TI  - Progressive postnatal motoneuron loss in mice lacking GDF-15.
AB  - Growth/differentiation factor-15 (GDF-15) is a widely expressed distant member of
      the TGF-beta superfamily with prominent neurotrophic effects on midbrain
      dopaminergic neurons. We show here that GDF-15-deficient mice exhibit progressive
      postnatal losses of spinal, facial, and trigeminal motoneurons. This deficit
      reaches a approximately 20% maximum at 6 months and is accompanied by losses of
      motor axons and significant impairment of rotarod skills. Similarly, sensory
      neurons in dorsal root ganglia (L4, L5) are reduced by 20%, whereas sympathetic
      neurons are not affected. GDF-15 is expressed and secreted by Schwann cells,
      retrogradely transported along adult sciatic nerve axons, and promotes survival
      of axotomized facial neurons as well as cultured motor, sensory, and sympathetic
      neurons. Despite striking similarities in the GDF-15 and CNTF knock-out
      phenotypes, expression levels of CNTF and other neurotrophic factors in the
      sciatic nerve were unaltered suggesting that GDF-15 is a genuine novel trophic
      factor for motor and sensory neurons.

PMID- 19864578
TI  - Selective expression of a sodium pump isozyme by cough receptors and evidence for
      its essential role in regulating cough.
AB  - We have identified a distinct subtype of airway vagal afferent nerve that plays
      an essential role in regulating the cough reflex. These afferents are exquisitely
      sensitive to punctate mechanical stimuli, acid, and decreases in extracellular
      chloride concentrations, but are insensitive to capsaicin, bradykinin, histamine,
      adenosine, serotonin, or changes in airway intraluminal pressures. In this study
      we used intravital imaging, retrograde neuronal tracing, and electrophysiological
      analyses to characterize the structural basis for their peculiar mechanical
      sensitivity and to further characterize the regulation of their excitability. In
      completing these experiments, we uncovered evidence for an essential role of an
      isozyme of Na(+)-K(+) ATPase in regulating cough. These vagal sensory neurons
      arise bilaterally from the nodose ganglia and are selectively and brilliantly
      stained intravitally with the styryl dye FM2-10. Cough receptor terminations are
      confined and adherent to the extracellular matrix separating the airway
      epithelium and smooth muscle layers, a site of extensive remodeling in asthma and
      chronic obstructive pulmonary disease. The cough receptor terminals uniquely
      express the alpha(3) subunit of Na(+)-K(+) ATPase. Intravital staining of cough
      receptors by FM2-10, cough receptor excitability in vitro, and coughing in vivo
      are potently and selectively inhibited by the sodium pump inhibitor ouabain.
      These data provide the first detailed morphological description of the peripheral
      terminals of the sensory nerves regulating cough and identify a selective
      molecular target for their modulation.

PMID- 19864579
TI  - Differential gene expression in the developing lateral geniculate nucleus and
      medial geniculate nucleus reveals novel roles for Zic4 and Foxp2 in visual and
      auditory pathway development.
AB  - Primary sensory nuclei of the thalamus process and relay parallel channels of
      sensory input into the cortex. The developmental processes by which these nuclei
      acquire distinct functional roles are not well understood. To identify novel
      groups of genes with a potential role in differentiating two adjacent sensory
      nuclei, we performed a microarray screen comparing perinatal gene expression in
      the principal auditory relay nucleus, the medial geniculate nucleus (MGN), and
      principal visual relay nucleus, the lateral geniculate nucleus (LGN). We
      discovered and confirmed groups of highly ranked, differentially expressed genes
      with qRT-PCR and in situ hybridization. A functional role for Zic4, a
      transcription factor highly enriched in the LGN, was investigated using Zic4-null
      mice, which were found to have changes in topographic patterning of
      retinogeniculate projections. Foxp2, a transcriptional repressor expressed
      strongly in the MGN, was found to be positively regulated by activity in the MGN.
      These findings identify roles for two differentially expressed genes, Zic4 and
      Foxp2, in visual and auditory pathway development. Finally, to test whether
      modality-specific patterns of gene expression are influenced by extrinsic
      patterns of input, we performed an additional microarray screen comparing the
      normal MGN to "rewired" MGN, in which normal auditory afferents are ablated and
      novel retinal inputs innervate the MGN. Data from this screen indicate that
      rewired MGN acquires some patterns of gene expression that are present in the
      developing LGN, including an upregulation of Zic4 expression, as well as novel
      patterns of expression which may represent unique processes of cross-modal
      plasticity.

PMID- 19864580
TI  - Proopiomelanocortin expression in both GABA and glutamate neurons.
AB  - Proopiomelanocortin (POMC) neurons have been intensively studied because of their
      essential role in regulating energy balance and body weight. Many effects of POMC
      neurons can be attributed to their release of cognate neuropeptides from
      secretory granules in axon terminals. However, these neurons also synaptically
      release non-peptide neurotransmitters. The aim of this study was to settle the
      controversy whether there are separate populations of POMC neurons that release
      GABA or glutamate. Transgenic mice expressing a red fluorescent protein
      [Discosoma red (DsRed)] driven by Pomc neuronal regulatory elements (POMC-DsRed)
      were crossed to mice that expressed green fluorescent protein (gfp) in GABAergic
      neurons (GAD67-gfp). Approximately 40% of POMC neurons in the arcuate nucleus of
      the double-transgenic mice expressed the GAD67-gfp transgene. In vitro
      neurotransmitter release was detected using whole-cell electrophysiologic
      recordings in cultured GAD67-gfp-positive and GAD67-gfp-negative POMC neurons
      that had formed recurrent synapses (autapses). Autapses from GAD67-gfp-positive
      neurons were uniformly GABAergic. In contrast, autapses from the GAD67-gfp
      negative POMC neurons exclusively exhibited postsynaptic currents mediated by
      glutamate. Together, these results indicate that there are two subpopulations of
      POMC neurons in the arcuate nucleus differentiated by their amino acid
      neurotransmitter phenotype. Whole-cell voltage-clamp recordings from POMC neurons
      in live brain slices indicated that GABAergic and glutamatergic POMC neurons are
      under similar presynaptic and postsynaptic regulation, although the GABAergic
      POMC neurons are smaller and have higher input resistance. GABAergic and
      glutamatergic POMC neurons may mediate distinct aspects of POMC neuron function,
      including the regulation of energy homeostasis.

PMID- 19864581
TI  - Permanent functional reorganization of retinal circuits induced by early long
      term visual deprivation.
AB  - Early sensory experience shapes the functional and anatomical connectivity of
      neuronal networks. Light deprivation alters synaptic transmission and modifies
      light response properties in the visual system, from retinal circuits to higher
      visual centers. These effects are more pronounced during a critical period in
      juvenile life and are mostly reversed by restoring normal light conditions. Here
      we show that complete light deprivation, from birth to periods beyond the
      critical period, permanently modifies the receptive field properties of retinal
      ganglion cells. Visual deprivation reduced both the strength of light responses
      in ganglion cells and their receptive field size. Light deprivation produced an
      imbalance in the ratio of inhibitory to excitatory inputs, with a shift toward
      larger inhibitory conductances. Ganglion cell receptive fields in visually
      deprived animals showed a spatial mismatch of inhibitory and excitatory inputs
      and inhibitory inputs were highly scattered over the receptive field. These
      results indicate that visual experience early in life is critical for the
      refinement of retinal circuits and for appropriate signaling of the
      spatiotemporal properties of visual stimuli, thus influencing the response
      properties of neurons in higher visual centers and their processing of visual
      information.

PMID- 19864582
TI  - Pattern motion selectivity of spiking outputs and local field potentials in
      macaque visual cortex.
AB  - The dorsal pathway of the primate visual cortex is involved in the processing of
      motion signals that are useful for perception and behavior. Along this pathway,
      motion information is first measured by the primary visual cortex (V1), which
      sends specialized projections to extrastriate regions such as the middle temporal
      area (MT). Previous work with plaid stimuli has shown that most V1 neurons
      respond to the individual components of moving stimuli, whereas some MT neurons
      are capable of estimating the global motion of the pattern. In this work, we show
      that the majority of neurons in the medial superior temporal area (MST), which
      receives input from MT, have this pattern-selective property. Interestingly, the
      local field potentials (LFPs) measured simultaneously with the spikes often
      exhibit properties similar to that of the presumptive feedforward input to each
      area: in the high-gamma frequency band, the LFPs in MST are as component
      selective as the spiking outputs of MT, and MT LFPs have plaid responses that are
      similar to the spiking outputs of V1. In the lower LFP frequency bands (beta and
      low gamma), component selectivity is very common, and pattern selectivity is
      almost entirely absent in both MT and MST. Together, these results suggest a
      surprisingly strong link between the sensory tuning of cortical LFPs and afferent
      inputs, with important implications for the interpretation of imaging studies and
      for models of cortical function.

PMID- 19864583
TI  - Beta-catenin signaling levels in progenitors influence the laminar cell fates of
      projection neurons.
AB  - The mechanisms underlying the timing of the laminar fate decisions during
      cortical neurogenesis remain poorly understood. Here we show that beta-catenin
      signaling in cortical neural precursors can regulate the laminar fate of their
      daughters. In ventricular zone neural precursors, beta-catenin signaling is
      higher when deep-layer neurons are being generated and lower when upper-layer
      neurons are being generated. Overactivation of beta-catenin in cortical
      precursors midway through corticogenesis increased the relative production of
      deep-layer neurons, while inhibition of signaling increased the relative
      production of upper-layer neurons. Furthermore, in late-gestation upper-layer
      precursors, overactive beta-catenin signaling was able to partially restore
      production of deep-layer neurons. These observations suggest that increased beta
      catenin signaling can reset the timing of cortical precursors to promote the
      production of deep-layer neurons, while inhibition of beta-catenin signaling
      advances the timing to promote upper-layer production.

PMID- 19864584
TI  - Control of cortical axon elongation by a GABA-driven Ca2+/calmodulin-dependent
      protein kinase cascade.
AB  - Ca(2+) signaling plays important roles during both axonal and dendritic growth.
      Yet whether and how Ca(2+) rises may trigger and contribute to the development of
      long-range cortical connections remains mostly unknown. Here, we demonstrate that
      two separate limbs of the Ca(2+)/calmodulin-dependent protein kinase kinase
      (CaMKK)-CaMKI cascades, CaMKK-CaMKIalpha and CaMKK-CaMKIgamma, critically
      coordinate axonal and dendritic morphogenesis of cortical neurons, respectively.
      The axon-specific morphological phenotype required a diffuse cytoplasmic
      localization and a strikingly alpha-isoform-specific kinase activity of CaMKI.
      Unexpectedly, treatment with muscimol, a GABA(A) receptor agonist, selectively
      stimulated elongation of axons but not of dendrites, and the CaMKK-CaMKIalpha
      cascade critically mediated this axonogenic effect. Consistent with these
      findings, during early brain development, in vivo knockdown of CaMKIalpha
      significantly impaired the terminal axonal extension and thereby perturbed the
      refinement of the interhemispheric callosal projections into the contralateral
      cortices. Our findings thus indicate a novel role for the GABA-driven CaMKK
      CaMKIalpha cascade as a mechanism critical for accurate cortical axon
      pathfinding, an essential process that may contribute to fine-tuning the
      formation of interhemispheric connectivity during the perinatal development of
      the CNS.

PMID- 19864585
TI  - Effects of the antipsychotic risperidone on dopamine synthesis in human brain
      measured by positron emission tomography with L-[beta-11C]DOPA: a stabilizing
      effect for dopaminergic neurotransmission?
AB  - Effects of antipsychotic drugs have widely been considered to be mediated by
      blockade of postsynaptic dopamine D(2) receptors. Effects of antipsychotics on
      presynaptic functions of dopaminergic neurotransmission might also be related to
      therapeutic effects of antipsychotics. To investigate the effects of
      antipsychotics on presynaptic functions of dopaminergic neurotransmission in
      relation with occupancy of dopamine D(2) receptors, changes in dopamine synthesis
      capacity by antipsychotics and occupancy of dopamine D(2) receptors were measured
      by positron emission tomography (PET) in healthy men. PET studies using
      [(11)C]raclopride and L-[beta-(11)C]DOPA were performed under resting condition
      and oral administration of single dose of the antipsychotic drug risperidone on
      separate days. Although occupancy of dopamine D(2) receptors corresponding dose
      of risperidone was observed, the changes in dopamine synthesis capacity by the
      administration of risperidone were not significant, nor was the relation between
      the occupancy of dopamine D(2) receptors and these changes. A significant
      negative correlation was observed between the baseline dopamine synthesis
      capacity and the changes in dopamine synthesis capacity by risperidone,
      indicating that this antipsychotic can be assumed to stabilize the dopamine
      synthesis capacity. The therapeutic effects of risperidone in schizophrenia might
      be related to such stabilizing effects on dopaminergic neurotransmission
      responsivity.

PMID- 19864588
TI  - Predicting recovery from muscle strains, a new take on "inflammation" and the
      Goldman Dilemma.

PMID- 19864589
TI  - BJSM reviews: A-Z of supplements: dietary supplements, sports nutrition foods and
      ergogenic aids for health and performance Part 2.

PMID- 19864586
TI  - What "works" in working memory? Separate systems for selection and updating of
      critical information.
AB  - Cognition depends critically on working memory, the active representation of a
      limited number of items over short periods of time. In addition to the
      maintenance of information during the course of cognitive processing, many tasks
      require that some of the items in working memory become transiently more
      important than others. Based on cognitive models of working memory, we
      hypothesized two complementary essential cognitive operations to achieve this: a
      selection operation that retrieves the most relevant item, and an updating
      operation that changes the focus of attention onto it. Using functional magnetic
      resonance imaging, high-resolution oculometry, and behavioral analysis, we
      demonstrate that these two operations are functionally and neuroanatomically
      dissociated. Updating the attentional focus elicited transient activation in the
      caudal superior frontal sulcus and posterior parietal cortex. In contrast,
      increasing demands on selection selectively modulated activation in rostral
      superior frontal sulcus and posterior cingulate/precuneus. We conclude that
      prioritizing one memory item over others invokes independent mechanisms of
      mnemonic retrieval and attentional focusing, each with its distinct
      neuroanatomical basis within frontal and parietal regions. These support the
      developing understanding of working memory as emerging from the interaction
      between memory and attentional systems.

PMID- 19864590
TI  - The ABCs of the anterior cruciate ligament: a primer for magnetic resonance
      imaging assessment of the normal, injured and surgically repaired anterior
      cruciate ligament.
AB  - This article reviews the magnetic resonance imaging (MRI) findings of the native
      and reconstructed anterior cruciate ligament (ACL). MRI is the most accurate non
      invasive modality to evaluate the ACL. Tears of the ACL manifest with direct and
      indirect signs. The reconstructed ACL has several complications including re-tear
      and anterior arthrofibrosis, which are also accurately assessed using MRI.

PMID- 19864591
TI  - IL-22 produced by human NK cells inhibits growth of Mycobacterium tuberculosis by
      enhancing phagolysosomal fusion.
AB  - We determined whether human NK cells could contribute to immune defenses against
      Mycobacterium tuberculosis through production of IL-22. CD3(-)CD56(+) NK cells
      produced IL-22 when exposed to autologous monocytes and gamma-irradiated M.
      tuberculosis, and this depended on the presence of IL-15 and IL-23, but not IL-12
      or IL-18. IL-15-stimulated NK cells expressed 10.6 times more DAP10 mRNA compared
      with control NK cells, and DAP10 siRNA inhibited IL-15-mediated IL-22 production
      by NK cells. Soluble factors produced by IL-15-activated NK cells inhibited
      growth of M. tuberculosis in macrophages, and this effect was reversed by anti-IL
      22. Addition of rIL-22 to infected macrophages enhanced phagolysosomal fusion and
      reduced growth of M. tuberculosis. We conclude that NK cells can contribute to
      immune defenses against M. tuberculosis through production of IL-22, which
      inhibits intracellular mycobacterial growth by enhancing phagolysosomal fusion.
      IL-15 and DAP-10 elicit IL-22 production by NK cells in response to M.
      tuberculosis.

PMID- 19864592
TI  - Bone marrow Ly6Chigh monocytes are selectively recruited to injured kidney and
      differentiate into functionally distinct populations.
AB  - Roles for monocyte/macrophages (Mphi) in directing the development of tissue
      fibrosis are increasingly recognized. Macrophages form a heterogeneous group of
      inflammatory leukocytes, and the mechanisms by which they acquire heterogeneity
      and its functional significance are unclear. We used the unilateral ureteral
      obstruction model of progressive kidney fibrosis to explore macrophage
      heterogeneity and function further. Unilateral ureteral obstruction kidney Mphis
      form three distinct subpopulations defined by the marker Ly6C, all of which are
      derived from a single Ly6C(high) bone marrow monocyte population selectively
      recruited to the kidney. Conditional ablation of these Mphis in vivo in CD11b-DTR
      mice is potently antifibrotic. The mRNA transcription profile of these
      populations is consistent with differential functional roles for each
      subpopulation, with Ly6C(low) macrophages transcribing genes consistent with
      selective profibrotic or M2-type function. Furthermore, bone marrow chimerism
      studies indicate that although resident kidney macrophages proliferate markedly
      to comprise up to 40% of the inflammatory macrophage population, they do not
      contribute to fibrosis. Our data identify Ly6C as a marker of functionally
      discrete tissue macrophage subsets and support a model of selective recruitment
      of Ly6C(high) bone marrow monocytes to the kidney that differentiate into three
      populations of kidney macrophages, including a profibrotic Ly6C(low) population.

PMID- 19864593
TI  - CXCR2 is required for neutrophilic airway inflammation and hyperresponsiveness in
      a mouse model of human rhinovirus infection.
AB  - Human rhinovirus (RV) infection is responsible for the majority of virus-induced
      asthma exacerbations. Using a mouse model of human RV infection, we sought to
      determine the requirement of CXCR2, the receptor for ELR-positive CXC chemokines,
      for RV-induced airway neutrophilia and hyperresponsiveness. Wild-type and CXCR2(
      /-) mice were inoculated intranasally with RV1B or sham HeLa cell supernatant.
      Following RV1B infection, CXCR2(-/-) mice showed reduced airway and lung
      neutrophils and cholinergic responsiveness compared with wild-type mice. Similar
      results were obtained in mice treated with neutralizing Ab to Ly6G, a neutrophil
      depleting Ab. Lungs from RV-infected, CXCR2(-/-) mice showed significantly
      reduced production of TNF-alpha, MIP-2/CXCL2, and KC/CXCL1 and lower expression
      of MUC5B compared with RV-treated wild-type mice. The requirement of TNF-alpha
      for RV1B-induced airway responses was tested using TNFR1(-/-) mice. TNFR1(-/-)
      animals displayed reduced airway responsiveness to RV1B, even when exogenous MIP
      2 was added to the airways. We conclude that CXCR2 is required for RV-induced
      neutrophilic airway inflammation and that neutrophil TNF-alpha release is
      required for airway hyperresponsiveness.

PMID- 19864594
TI  - Cupressaceae pollen grains modulate dendritic cell response and exhibit IgE
      inducing adjuvant activity in vivo.
AB  - Pollen is considered a source of not only allergens but also immunomodulatory
      substances, which could play crucial roles in sensitization and/or the
      exacerbation of allergies. We investigated how allergenic pollens from different
      plant species (Japanese cedar and Japanese cypress, which belong to the
      Cupressaceae family, and birch, ragweed, and grass) modulate murine bone marrow
      derived dendritic cell (DC) responses and examined the effect of Cupressaceae
      pollen in vivo using mice. DCs were stimulated with pollen extracts or grains in
      the presence or absence of LPS. Cell maturation and cytokine production in DCs
      were analyzed by flow cytometry, ELISA, and/or quantitative PCR. Pollen extracts
      suppressed LPS-induced IL-12 production and the effect was greatest for birch and
      grass. Without LPS, pollen grains induced DC maturation and cytokine production
      without IL-12 secretion and the response, for which TLR 4 was dispensable, was
      greatest for the Cupressaceae family. Intranasal administration of Cupressaceae
      pollen in mice induced an elevation of serum IgE levels and airway eosinophil
      infiltration. Coadministration of ovalbumin with Cupressaceae pollen grains
      induced ovalbumin-specific IgE responses associated with eosinophil infiltration.
      The results suggest that modulation of DC responses by pollen differs among the
      plant families via (1) the promotion of DC maturation and cytokine production by
      direct contact and/or (2) the inhibition of IL-12 production by soluble factors.
      The strong DC stimulatory activity in vitro and IgE-inducing activity in mice
      support the clinical relevance of Cupressaceae pollen to allergies in humans.

PMID- 19864595
TI  - CMV-specific TCR-transgenic T cells for immunotherapy.
AB  - Reactivation of CMV can cause severe disease after allogeneic hemopoietic stem
      cell transplantation. Adoptive T cell therapy was successfully used for patients
      who had received transplants from CMV-positive donors. However, patients with
      transplants from CMV-negative donors are at highest risk, and an adoptive therapy
      is missing because CMV-specific T cells are not available from such donors. To
      address this problem, we used retroviral transfer of CMV-specific TCR genes. We
      generated CMV-specific T cell clones of several HLA restrictions recognizing the
      endogenously processed Ag pp65. The genes of four TCRs were cloned and
      transferred to primary T cells from CMV-negative donors. These CMV-TCR-transgenic
      T cells displayed a broad spectrum of important effector functions (secretion of
      IFN-gamma and IL-2, cytotoxicity, proliferation) in response to endogenously
      processed pp65 and could be enriched and expanded by strictly Ag-specific
      stimulation. Expansion of engineered T cells was accompanied by an increase in
      specific effector functions, indicating that the transferred specificity is
      stable and fully functional. Hence, we expect these CMV-TCR-transgenic T cells to
      be effective in controlling acute CMV disease and establishing an antiviral
      memory.

PMID- 19864596
TI  - AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a
      transient localized innate immune response leading to enhanced adaptive immunity.
AB  - Adjuvant System 04 (AS04) combines the TLR4 agonist MPL (3-O-desacyl-4'
      monophosphoryl lipid A) and aluminum salt. It is a new generation TLR-based
      adjuvant licensed for use in human vaccines. One of these vaccines, the human
      papillomavirus (HPV) vaccine Cervarix, is used in this study to elucidate the
      mechanism of action of AS04 in human cells and in mice. The adjuvant activity of
      AS04 was found to be strictly dependent on AS04 and the HPV Ags being injected at
      the same i.m. site within 24 h of each other. During this period, AS04
      transiently induced local NF-kappaB activity and cytokine production. This led to
      an increased number of activated Ag-loaded dendritic cells and monocytes in the
      lymph node draining the injection site, which further increased the activation of
      Ag-specific T cells. AS04 was also found to directly stimulate those APCs in
      vitro but not directly stimulate CD4(+) T or B lymphocytes. These AS04-induced
      innate responses were primarily due to MPL. Aluminum salt appeared not to
      synergize with or inhibit MPL, but rather it prolonged the cytokine responses to
      MPL at the injection site. Altogether these results support a model in which the
      addition of MPL to aluminum salt enhances the vaccine response by rapidly
      triggering a local cytokine response leading to an optimal activation of APCs.
      The transient and confined nature of these responses provides further supporting
      evidence for the favorable safety profile of AS04 adjuvanted vaccines.

PMID- 19864597
TI  - The novel lipopolysaccharide-binding protein CRISPLD2 is a critical serum protein
      to regulate endotoxin function.
AB  - LPS is an immunostimulatory component of Gram-negative bacteria. Acting on the
      immune system in a systemic fashion, LPS exposes the body to the hazard of septic
      shock. In this study we report that cysteine-rich secretory protein LCCL domain
      containing 2 (CRISPLD2/Crispld2; human and mouse/rat versions, respectively),
      expressed by multitissues and leukocytes, is a novel LPS-binding protein. As a
      serum protein, median CRISPLD2 concentrations in health volunteers and umbilical
      cord blood samples are 607 microg/ml and 290 microg/ml, respectively. Human
      peripheral blood granulocytes and mononuclear cells including monocytes, NK
      cells, and T cells spontaneously release CRISPLD2 (range, 0.2-0.9 microg/ml) and
      enhance CRISPLD2 secretion (range, 1.5-4.2 microg/ml) in response to stimulation
      of both LPS and humanized anti-human TLR4-IgA Ab in vitro. CRISPLD2 exhibits
      significant LPS binding affinity similar to that of soluble CD14, prevents LPS
      binding to target cells, reduces LPS-induced TNF-alpha and IL-6 production, and
      protects mice against endotoxin shock. In in vivo experiments, serum Crispld2
      concentrations increased in response to a nontoxic dose of LPS and correlated
      negatively with LPS lethality, suggesting that CRISPLD2 serum concentrations not
      only are indicators of the degree of a body's exposure to LPS but also reflect an
      individual's LPS sensitivity.

PMID- 19864599
TI  - Type I interferons produced by resident renal cells may promote end-organ disease
      in autoantibody-mediated glomerulonephritis.
AB  - Increased Type I IFNs or IFN-I have been associated with human systemic lupus
      erythematosus. Interestingly augmenting or negating IFN-I activity in murine
      lupus not only modulates systemic autoimmunity, but also impacts lupus nephritis,
      suggesting that IFN-I may be acting at the level of the end-organ. We find
      resident renal cells to be a dominant source of IFN-I in an experimental model of
      autoantibody-induced nephritis. In this model, augmenting IFN-I amplified
      antibody-triggered nephritis, whereas ablating IFN-I activity ameliorated
      disease. One mechanism through which increased IFN-I drives immune-mediated
      nephritis might be operative through increased recruitment of inflammatory
      monocytes and neutrophils, though this hypothesis needs further validation.
      Collectively, these studies indicate that an important contribution of IFN-I
      toward the disease pathology seen in systemic autoimmunity may be exercised at
      the level of the end-organ.

PMID- 19864598
TI  - Recognition of fungal protease activities induces cellular activation and
      eosinophil-derived neurotoxin release in human eosinophils.
AB  - Eosinophils are multifunctional leukocytes implicated in the pathogenesis of
      asthma and in immunity to certain organisms. Associations between exposure to an
      environmental fungus, such as Alternaria, and asthma have been recognized
      clinically. Protease-activated receptors (PARs) are G protein-coupled receptors
      that are cleaved and activated by serine proteases, but their roles in innate
      immunity remain unknown. We previously found that human eosinophils respond
      vigorously to Alternaria organisms and to the secretory product(s) of Alternaria
      with eosinophils releasing their proinflammatory mediators. In this study, we
      investigated the roles of protease(s) produced by Alternaria and of PARs
      expressed on eosinophils in their immune responses against fungal organisms. We
      found that Alternaria alternata produces aspartate protease(s) and that human
      peripheral blood eosinophils degranulate in response to the cell-free extract of
      A. alternata. Eosinophils showed an increased intracellular calcium concentration
      in response to Alternaria that was desensitized by peptide and protease ligands
      for PAR-2 and inhibited by a PAR-2 antagonistic peptide. Alternaria-derived
      aspartate protease(s) cleaved PAR-2 to expose neo-ligands; these neo-ligands
      activated eosinophil degranulation in the absence of proteases. Finally,
      treatment of Alternaria extract with aspartate protease inhibitors, which are
      conventionally used for HIV-1 and other microbes, attenuated the eosinophils'
      responses to Alternaria. Thus, fungal aspartate protease and eosinophil PAR-2
      appear critical for the eosinophils' innate immune response to certain fungi,
      suggesting a novel mechanism for pathologic inflammation in asthma and for host
      pathogen interaction.

PMID- 19864600
TI  - Human follicular lymphoma CD39+-infiltrating T cells contribute to adenosine
      mediated T cell hyporesponsiveness.
AB  - Our previous work has demonstrated that human follicular lymphoma (FL)
      infiltrating T cells are anergic, in part due to suppression by regulatory T
      cells. In this study, we identify pericellular adenosine, interacting with T cell
      associated G protein-coupled A(2A/B) adenosine receptors (AR), as contributing to
      FL T cell hyporesponsiveness. In a subset of FL patient samples, treatment of
      lymph node mononuclear cells (LNMC) with specific A(2A/B) AR antagonists results
      in an increase in IFN-gamma or IL-2 secretion upon anti-CD3/CD28 Ab stimulation,
      as compared with that seen without inhibitors. In contrast, treatment with an
      A(1) AR antagonist had no effect on cytokine secretion. As the rate limiting step
      for adenosine generation from pericellular ATP is the ecto-ATPase CD39, we next
      show that inhibition of CD39 activity using the inhibitor ARL 67156 partially
      overcomes T cell hyporesponsiveness in a subset of patient samples. Phenotypic
      characterization of LNMC demonstrates populations of CD39-expressing CD4(+) and
      CD8(+) T cells, which are overrepresented in FL as compared with that seen in
      normal or reactive nodes, or normal peripheral blood. Thirty percent of the FL
      CD4(+)CD39(+) T cells coexpress CD25(high) and FOXP3 (consistent with regulatory
      T cells). Finally, FL or normal LNMC hydrolyze ATP in vitro, in a dose- and time
      dependent fashion, with the rate of ATP consumption being associated with the
      degree of CD39(+) T cell infiltration. Together, these results support the
      finding that the ATP-ectonucleotidase-adenosine system mediates T cell anergy in
      a human tumor. In addition, these studies suggest that the A(2A/B) AR as well as
      CD39 are novel pharmacological targets for augmenting cancer immunotherapy.

PMID- 19864601
TI  - CD36 and TLR interactions in inflammation and phagocytosis: implications for
      malaria.
AB  - CD36 participates in macrophage internalization of a variety of particles, and
      has been implicated in inflammatory responses to many of these ligands. To what
      extent CD36 cooperates with other receptors in mediating these processes remains
      unclear. Because CD36 has been shown to cooperate with TLR2, we investigated the
      roles and interactions of CD36 and TLRs in inflammation and phagocytosis. Using
      Ab-induced endocytosis of CD36 and phagocytosis of erythrocytes displaying Abs to
      CD36, we show that selective engagement and internalization of this receptor did
      not lead to proinflammatory cytokine production by primary human and murine
      macrophages. In addition, CD36-mediated phagocytosis of Plasmodium falciparum
      malaria-parasitized erythrocytes (PEs), which contain parasite components that
      activate TLRs, also failed to induce cytokine secretion from primary macrophages.
      Furthermore, we demonstrate that CD36-mediated internalization did not require
      TLR2 or the TLR-signaling molecule IRAK4. However, macrophage pretreatment with
      TLR agonists markedly stimulated particle uptake via CD36. Similarly, PE uptake
      was unaffected by TLR deficiency, but in wild-type cells was increased by
      pretreatment with purified P. falciparum glycosylphosphatidylinositols, which
      activate TLR2. Our findings indicate that CD36 must cooperate with other
      receptors such as TLRs to participate in cytokine responses. Although purified P.
      falciparum components activate TLRs, CD36-mediated internalization of intact PEs
      is not inflammatory. Further, CD36 mediates internalization of particles,
      including PEs, independently of TLR signaling, but can functionally cooperate
      with TLRs to enhance internalization.

PMID- 19864602
TI  - The bile acid receptor FXR is a modulator of intestinal innate immunity.
AB  - The farnesoid X receptor (FXR) is a bile acid-regulated nuclear receptor
      expressed in enterohepatic tissues. In this study we investigated whether FXR is
      expressed by cells of innate immunity and regulates inflammation in animal models
      of colitis. Acute (7 days) and chronic (8 wk) colitis were induced in wild-type
      and FXR(-/-) mice by intrarectal administration of trinitrobenzensulfonic acid or
      by 7-day administration of 5% dextran sulfate in drinking water. The results of
      this experiment demonstrate that FXR is expressed by and exerts counterregulatory
      effects on cells of innate immunity. Exposure of LPS-activated macrophages to 6
      ethyl chenodeoxycholic acid (6E-CDCA; INT-747) a synthetic FXR ligand, results in
      a reciprocal regulation of NF-kappaB dependent-genes (TNF-alpha, IL-1beta, IL-6,
      COX-1, COX-2, and iNOS) and induction of SHP, a FXR-regulated gene. FXR
      activation stabilizes the nuclear corepressor NCoR on the NF-kappaB responsive
      element on the IL-1beta promoter. Colon inflammation in Crohn's disease patients
      and in rodent models of colitis is associated with a reduced expression of FXR
      mRNA. Using two rodent models of colon inflammation, we show that progression of
      these immune-mediated disorders is exacerbated in FXR(-/-) mice (p < 0.01). In
      vivo treatment with INT-747 attenuates organ injury and immune cell activation.
      FXR activation increased the colon expression of I-BABP, FXR, and SHP while
      reducing IL-1beta, IL-2, IL-6, TNF-alpha, and IFN-gamma mRNA expression and
      attenuating disease severity. In aggregate, these findings provide evidence that
      FXR is an essential component of a network of nuclear receptors that regulate
      intestinal innate immunity and homeostasis.

PMID- 19864603
TI  - Long double-stranded RNA induces an antiviral response independent of IFN
      regulatory factor 3, IFN-beta promoter stimulator 1, and IFN.
AB  - Virus infection elicits a robust innate antiviral response dominated by the
      production of type 1 IFN. In nonprofessional innate immune cells such as
      fibroblasts, type 1 IFN is rapidly produced following the recognition of viral
      dsRNA and the subsequent activation of the constitutively expressed transcription
      factor IFN regulatory factor 3 (IRF3). Although origin, localization, and length
      are factors in mediating dsRNA recognition and binding by cellular dsRNA-binding
      proteins, the biological significance of differential dsRNA binding is unclear,
      since the subsequent signaling pathways converge on IRF3. In this study, we show
      a dsRNA length-dependent activation of IRFs, IFNs, and IFN-stimulated genes in
      mouse fibroblasts. The length dependence was exacerbated in fibroblasts deficient
      in the mitochondria-associated adaptor IFN-beta promoter stimulator 1 and IRF3,
      suggesting that antiviral gene induction mediated by short and long dsRNA
      molecules is predominantly IFN-beta promoter stimulator 1 and IRF3 dependent and
      independent, respectively. Furthermore, we provide evidence of an innate
      antiviral response in fibroblasts in the absence of both IRF3 and type 1 IFN
      induction. Even with these key modulators missing, a 60-90% inhibition of virus
      replication was observed following 24-h treatment with short or long dsRNA
      molecules, respectively. These data provide evidence of a novel antiviral pathway
      that is dependent on dsRNA length, but independent of the type 1 IFN system.

PMID- 19864604
TI  - Complement activation by CpG in a human whole blood loop system: mechanisms and
      immunomodulatory effects.
AB  - Phosphorothioate oligodeoxynucleotides can activate complement, and experimental
      murine studies have revealed differential effects upon simultaneous TLR
      stimulation and complement activation compared with either event alone. We set
      out to investigate the immune stimulatory effects of CpG 2006 in fresh non
      anticoagulated human blood with or without presence of active complement. We also
      sought to elucidate the mechanism behind complement activation upon stimulation
      with phosphorothioate CpG 2006. In a human blood loop system, both backbone and
      sequence-specific effects by CpG were counteracted by selective inhibition of C3.
      Furthermore, DNA backbone-mediated CD40 and CD83 expression on monocytes and
      sequence-specific IL-6 and TNF production were reduced by complement inhibition.
      CpG-induced complement activation occurred via either the classical or the
      alternative pathway and deposits of both IgM and properdin, two activators of
      complement, were detected on CpG after incubation with EDTA plasma. Quartz
      crystal microbalance with dissipation monitoring demonstrated alternative pathway
      convertase build-up onto CpG as a likely pathway to initiate and sustain
      complement activation. Specific inhibition of C3 suppressed CpG 2006 uptake into
      monocytes indicating that C3 fragments are involved in CpG internalization. The
      interplay between complement and TLR9 signaling demonstrated herein warrants
      further investigation.

PMID- 19864605
TI  - C1q differentially modulates phagocytosis and cytokine responses during ingestion
      of apoptotic cells by human monocytes, macrophages, and dendritic cells.
AB  - C1q, the first component of the classical complement pathway, is also a pattern
      recognition receptor involved in the recognition and clearance of apoptotic
      cells. C1q deficiency in humans leads to development of lupus-like autoimmune
      disease, and it has been speculated that impaired clearance of apoptotic cells
      may contribute to disease development. Since phagocytes initiate specific and
      appropriate immune responses as a result of initial ligand-receptor interactions,
      regulation of gene expression by C1q may also contribute to the sculpting of an
      immune response to the ingested "self-Ags." In this study, the role of C1q in
      apoptotic cell clearance and subsequent modulation of cytokine release by
      phagocytes was assessed including donor matched human monocytes, monocyte-derived
      macrophages (HMDMs), and dendritic cells (DCs). First, C1q binding is much
      greater to late compared with early apoptotic cells. Second, C1q binding to
      apoptotic cells significantly enhanced the levels of ingestion by monocytes but
      had no effect on HMDM and DC uptake. Third, in the presence of serum, C1q bound
      to apoptotic cells, activated the complement pathway, leading to C3b deposition,
      and enhancement of uptake of apoptotic cells by monocytes, HMDMs, and DCs.
      Finally, although C1q, either immobilized on a plate or bound to apoptotic cells,
      modulates the LPS-induced cytokine levels released by human monocytes, HMDMs, and
      DCs toward a more limited immune response, both the degree and direction of
      modulation differed significantly depending on the differentiation state of the
      phagocyte, providing further evidence of the integration of these cell- and
      environment-specific signals in determining appropriate immune responses.

PMID- 19864606
TI  - Chemokine-like receptor-1 expression by central nervous system-infiltrating
      leukocytes and involvement in a model of autoimmune demyelinating disease.
AB  - We examined the involvement of chemokine-like receptor-1 (CMKLR1) in experimental
      autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Upon EAE
      induction by active immunization with myelin oligodendrocyte glycoprotein amino
      acids 35-55 (MOG(35-55)), microglial cells and CNS-infiltrating myeloid dendritic
      cells expressed CMKLR1, as determined by flow cytometric analysis. In addition,
      chemerin, a natural ligand for CMKLR1, was up-regulated in the CNS of mice with
      EAE. We found that CMKLR1-deficient (CMKLR1 knockout (KO)) mice develop less
      severe clinical and histologic disease than their wild-type (WT) counterparts.
      CMKLR1 KO lymphocytes proliferate and produce proinflammatory cytokines in vitro,
      yet MOG(35-55)-reactive CMKLR1 KO lymphocytes are deficient in their ability to
      induce EAE by adoptive transfer to WT or CMKLR1 KO recipients. Moreover, CMKLR1
      KO recipients fail to fully support EAE induction by transferred MOG-reactive WT
      lymphocytes. The results imply involvement of CMKLR1 in both the induction and
      effector phases of disease. We conclude that CMKLR1 participates in the
      inflammatory mechanisms of EAE and represents a potential therapeutic target in
      multiple sclerosis.

PMID- 19864607
TI  - Chronic CD70-driven costimulation impairs IgG responses by instructing T cells to
      inhibit germinal center B cell formation through FasL-Fas interactions.
AB  - CD70 provides costimulation that enhances effector T cell differentiation upon
      binding of its receptor, CD27. During chronic immune activation, CD70 is
      constitutively expressed on activated immune cells, and this induces T cell
      driven disruption of neutralizing Ab responses via an unknown mechanism. We used
      CD70-transgenic mice to investigate the effect of constitutive expression of CD70
      on T cell-dependent B cell responses. CD70 induced up-regulation of the B cell
      follicle homing chemokine receptor CXCR5 on T cells, enabling not only CD4 but
      also CD8 T cells to infiltrate the B cell follicles. CD70-transgenic mice failed
      to develop productive germinal center formation and displayed impaired IgG Ab
      responses. Defective germinal center B cell differentiation was critically
      dependent on CD70-mediated CD27 signaling in T cells, and involved Fas-dependent
      impairment of germinal center B cell differentiation. Thus, CD70-driven
      costimulation enables T cells to terminate B cell responses, thereby compromising
      durable Ab production. Our findings imply that the CD70- and CD27-driven
      costimulatory axis may be involved in shutdown of B cell responses before
      clearance of Ag. Because CD70 is expressed constitutively in chronic viral
      infections such as HIV-1 infection, this mechanism may also contribute to defects
      in humoral immunity associated with this disease.

PMID- 19864609
TI  - Defining the turkey MHC: sequence and genes of the B locus.
AB  - The MHC, the most polymorphic and gene dense region in the vertebrate genome,
      contains many loci essential to immunity. In mammals, this region spans
      approximately 4 Mb. Studies of avian species have found the MHC to be greatly
      reduced in size and gene content with an overall locus organization differing
      from that of mammals. The chicken MHC has been mapped to two distinct regions
      (MHC-B and -Y) of a single chromosome. MHC-B haplotypes possess tightly linked
      genes encoding the classical MHC molecules and few other disease resistance
      genes. Furthermore, chicken haplotypes possess a dominantly expressed class I and
      class II B locus that have a significant effect on the progression or regression
      of pathogenic disease. In this study, we present the MHC-B region of the turkey
      (Meleagris gallopavo) as a similarly constricted locus, with 34 genes identified
      within a 0.2-Mb region in near-perfect synteny with that of the chicken MHC-B.
      Notable differences between the two species are three BG and class II B loci in
      the turkey compared with one BG and two class II B loci in the chicken MHC-B. The
      relative size and high level of similarity of the turkey MHC in relation to that
      of the chicken suggest that similar associations with disease susceptibility and
      resistance may also be found in turkey.

PMID- 19864608
TI  - Ca2+ waves initiate antigen-stimulated Ca2+ responses in mast cells.
AB  - Ca(2+) mobilization is central to many cellular processes, including stimulated
      exocytosis and cytokine production in mast cells. Using single cell stimulation
      by IgE-specific Ag and high-speed imaging of conventional or genetically encoded
      Ca(2+) sensors in rat basophilic leukemia and bone marrow-derived rat mast cells,
      we observe Ca(2+) waves that originate most frequently from the tips of extended
      cell protrusions, as well as Ca(2+) oscillations throughout the cell that usually
      follow the initiating Ca(2+) wave. In contrast, Ag conjugated to the tip of a
      micropipette stimulates local, repetitive Ca(2+) puffs at the region of cell
      contact. Initiating Ca(2+) waves are observed in most rat basophilic leukemia
      cells stimulated with soluble Ag and are sensitive to inhibitors of Ca(2+)
      release from endoplasmic reticulum stores and to extracellular Ca(2+), but they
      do not depend on store-operated Ca(2+) entry. Knockdown of transient receptor
      potential channel (TRPC)1 and TRPC3 channel proteins by short hairpin RNA reduces
      the sensitivity of these cells to Ag and shifts the wave initiation site from
      protrusions to the cell body. Our results reveal spatially encoded Ca(2+)
      signaling in response to immunoreceptor activation that utilizes TRPC channels to
      specify the initiation site of the Ca(2+) response.

PMID- 19864610
TI  - Dendritic cell function in allostimulation is modulated by C5aR signaling.
AB  - Regulation of T cell immunity by C5a has been suggested from recent studies.
      However, the underlying mechanisms, particularly the involved cells and
      biochemical basis, are not well defined. In this study, the direct modulation of
      dendritic cell (DC) activation and its function in T cell stimulation by C5a-C5aR
      interaction and the involved signaling pathways were investigated. We show that
      DCs from C5aR(-/-) mice and normal DCs treated with C5aR antagonist have less
      activated phenotype characterized with increased IL-10 and decreased IL-12p70
      production in response to LPS stimulation, lowered surface expression of MHC
      class II, B7.2, and consequently have reduced capacity to stimulate allospecific
      T cells. Conversely, C5a stimulation up-regulates DC activation and its function
      in allostimulation. Furthermore, stimulation of C5aR mediates the inhibition of
      cAMP production and protein kinase A activity and is involved in activation of
      PI3K/AKT and NF-kappaB signaling in DCs. These results demonstrate that C5a acts
      directly on C5aR expressed on DCs resulting in the cell activation and
      subsequently enhances its capacity for allospecific T cell stimulation. It also
      suggests that NF-kappaB signaling induced by down-regulation of cAMP/ protein
      kinase A pathway and up-regulation of PI3K/AKT pathway following C5a stimulation
      may contribute to up-regulation of DC function.

PMID- 19864611
TI  - Outside-in signal transmission by conformational changes in integrin Mac-1.
AB  - Intracellular signals associated with or triggered by integrin ligation can
      control cell survival, differentiation, proliferation, and migration. Despite
      accumulating evidence that conformational changes regulate integrin affinity to
      its ligands, how integrin structure regulates signal transmission from the
      outside to the inside of the cell remains elusive. Using fluorescence resonance
      energy transfer, we addressed whether conformational changes in integrin Mac-1
      are sufficient to transmit outside-in signals in human neutrophils. Mac-1
      conformational activation induced by ligand occupancy or activating Ab binding,
      but not integrin clustering, triggered similar patterns of intracellular protein
      tyrosine phosphorylation, including Akt phosphorylation, and inhibited
      spontaneous neutrophil apoptosis, indicating that global conformational changes
      are critical for Mac-1-dependent outside-in signal transduction. In neutrophils
      and myeloid K562 cells, ligand ICAM-1 or activating Ab binding promoted
      switchblade-like extension of the Mac-1 extracellular domain and separation of
      the alpha(M) and beta(2) subunit cytoplasmic tails, two structural hallmarks of
      integrin activation. These data suggest the primacy of global conformational
      changes in the generation of Mac-1 outside-in signals.

PMID- 19864612
TI  - Differential cytokine production and bystander activation of autoreactive B cells
      in response to CpG-A and CpG-B oligonucleotides.
AB  - Synthetic oligonucleotides containing CpG motifs have been shown to induce
      proliferation, differentiation, and cytokine production in B cells, macrophages,
      and dendritic cells through a TLR9-dependent mechanism. A class (CpG-A) and B
      class (CpG-B) oligonucleotides display distinct physical properties. CpG-A, but
      not CpG-B, can multimerize to form exceedingly large lattices. CpG-A cannot
      effectively activate B cells but does induce plasmacytoid dendritic cells to
      produce high levels of IFNalpha, while CpG-B is a potent B cell mitogen. In this
      study, we report that CpG-A is internalized by B cells, and CpG-A and CpG-B
      accumulate in distinct intracellular compartments. When present in the form of an
      immune complex (CpG-A IC), CpG-A is taken up more efficiently by AM14 IgG2a
      specific B cells, and elicits a robust TLR9-dependent B cell proliferative
      response. B cells proliferating comparably and in a TLR9-dependent fashion in
      response to CpG-A IC and CpG-B exhibited distinct cytokine profiles. CpG-A IC
      induced enhanced production of RANTES and markedly reduced levels of IL-6 when
      compared with CpG-B. We also found that engagement of the AM14 BCR by a protein
      IC, which cannot by itself induce proliferation, promoted TLR9-dependent but BCR
      independent proliferation by bystander CpG-A or fragments of mammalian dsDNA.
      These data identify direct and indirect mechanisms by which BCR engagement
      facilitates access of exogenous ligands to TLR9-associated compartments and
      subsequent B cell activation.

PMID- 19864613
TI  - A major role for the minor capsid protein of human papillomavirus type 16 in
      immune escape.
AB  - High-risk human papillomavirus (HPV) infection of the cervical epithelium is
      causally linked with the generation of cervical cancer. HPV does not activate
      Langerhans cells (LC), the APC at the site of infection, leading to immune
      evasion. The HPV protein responsible for inducing this immune escape has not been
      determined. We demonstrate that LC exposed to the minor capsid protein L2 in
      HPV16L1L2 virus-like particles do not phenotypically or functionally mature.
      However, HPV16L1 virus-like particles significantly induce activation of LC. Our
      data suggest that the L2 protein plays a specific role in the induction of this
      immune escape of HPV16 through the manipulation of LC. This novel function is the
      first immune modulating action attributed to the L2 protein and adds
      significantly to our understanding of the mechanism of HPV immune escape.

PMID- 19864614
TI  - Attenuation of phencyclidine-induced object recognition deficits by the
      combination of atypical antipsychotic drugs and pimavanserin (ACP 103), a 5
      hydroxytryptamine(2A) receptor inverse agonist.
AB  - Subchronic administration of the N-methyl-d-aspartate receptor antagonist,
      phencyclidine (PCP), in rodents has been shown to produce impairment in novel
      object recognition (NOR), a model of visual learning and memory. We tested the
      hypothesis that the selective 5-HT(2A) inverse agonists, pimavanserin and (R)-(+)
      alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl]-4-piperidinemethanol
      (M100907), would potentiate subeffective doses of atypical antipsychotic drugs
      (APDs) to reverse the NOR deficits. Female rats received vehicle or PCP (2 mg/kg
      b.i.d.) for 7 days, followed by a 7-day washout. Pimavanserin (3 mg/kg) or
      M100907 (1 mg/kg) alone, or four atypicial APDs, risperidone (0.05-0.1 mg/kg),
      melperone (1-3 mg/kg), olanzapine (1-2 mg/kg), or N-desmethylclozapine (1-2
      mg/kg), and the typical APD, haloperidol (0.05-0.1 mg/kg), were administered
      alone, or in combination with pimavanserin or M100907, before NOR testing. The
      exploration times of objects during 3-min acquisition and retention trials,
      separated by a 1-min interval, were compared by analysis of variance. Vehicle-,
      but not PCP-treated, animals, explored the novel object significantly more than
      the familiar in the retention trial (p < 0.05-0.01). Pretreatment with the higher
      doses of the atypical APDs, but not pimavanserin, M100907, or haloperidol alone,
      reversed the effects of PCP. The effect of risperidone was blocked by haloperidol
      pretreatment. Coadministration of pimavanserin or M100907, with ineffective doses
      of the atypical APDs, but not haloperidol, also reversed the PCP-induced deficit
      in NOR. These results support the importance of 5-hydroxytryptamine(2A) receptor
      blockade relative to D(2) receptor blockade in the ability of atypicals to
      ameliorate the effect of subchronic PCP, a putative measure of cognitive
      dysfunction in schizophrenia.

PMID- 19864615
TI  - The aminoglycosides modulate the acid-sensing ionic channel currents in dorsal
      root ganglion neurons from the rat.
AB  - Acid-sensing ionic channels (ASICs) have been shown to have a significant role in
      a growing number of physiological and pathological processes, such as
      nociception, synaptic transmission and plasticity, mechanosensation, and acidosis
      induced neuronal injury. The discovery of pharmacological agents targeting ASICs
      has significant therapeutic potential and use as a research tool. In our work, we
      studied the action of transient perfusion (5-15 s) of aminoglycosides (AGs)
      (streptomycin and neomycin) on the proton-gated ionic currents in dorsal root
      ganglion (DRG) neurons of the rat and in human embryonic kidney (HEK)-293 cells.
      In DRG neurons, streptomycin and neomycin (30 microM) produced a significant,
      concentration-dependent, and reversible reduction in the amplitude of the proton
      gated current, and a slowing of the desensitization rate of the ASIC current.
      Gentamycin (30 microM) also showed a significant reversible action on the ASIC
      currents. The curves of the pH effect for streptomycin and neomycin indicated
      that their effect was not significantly affected by pH. In HEK-293 cells,
      streptomycin (30 microM) produced a significant reduction in the amplitude of the
      proton-gated current. Neomycin and gentamycin had no significant action.
      Reduction of extracellular Ca(2+) concentration produced a significant increase
      in the action of streptomycin and neomycin on the desensitization time course of
      ASIC currents. These results indicate that ASICs are molecular targets for AGs,
      which may contribute to the understanding of their actions on excitable cells.
      Moreover, AGs may constitute a source to develop novel molecules with a greater
      affinity, specificity, and selectivity for the different ASIC subunits.

PMID- 19864617
TI  - Mechanistic insight from in silico pharmacokinetic experiments: roles of P
      glycoprotein, Cyp3A4 enzymes, and microenvironments.
AB  - Saquinavir exhibits paradoxical transport across modified Caco-2 cell monolayers
      (doi: 10.1124/jpet.103.056390) expressing P-glycoprotein and Cyp3A4. The data
      implicate complicated intracellular transport mechanisms. Drawing on recent
      discrete event modeling and simulation advances, we built an in silico analog of
      the confluent, asymmetric cell monolayer used in the cited work. We call it in
      silico experimental Caco-2 (cell monolayer) culture (ISECC). Concrete, working,
      hypothesized spatial mechanisms were implemented. Validation was achieved when in
      silico experimental results met similarity measure (SM) expectations that
      targeted 16 wet-lab experimental conditions. Initial mechanistic hypotheses
      turned out to be necessary parts of a more complicated explanation. We progressed
      through four stages of an iterative refinement and validation protocol that
      enabled and facilitated discovery of plausible, new mechanistic details. The
      process exercised abductive reasoning, a primary means of scientific knowledge
      creation and creative cognition. The ISECC that survived the most stringent SM
      challenge produced transport data that was statistically indistinguishable from
      referent wet-lab observations. It required a 7:1 ratio of apical transporters to
      metabolizing enzymes, a 97% reduction of efflux activity by an inhibitor, a
      biased distribution of metabolizing enzymes, heterogeneous intracellular spaces,
      and restrictions on intracellular drug movement. Experimenting on synthetic
      analogs such as ISECC provides a former unavailable means of discovering new
      mechanistic details and testing their plausibility. The approach thus provides a
      powerful new expansion of the scientific method: an independent, scientific means
      to challenge, explore, better understand, and improve any inductive mechanism
      and, importantly, the assumptions on which it rests.

PMID- 19864616
TI  - The d5 dopamine receptor mediates large-conductance, calcium- and voltage
      activated potassium channel activation in human coronary artery smooth muscle
      cells.
AB  - Large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channels
      hyperpolarize coronary artery smooth muscle cells, causing vasorelaxation.
      Dopamine activates BK(Ca) channels by stimulating D(1)-like receptor-mediated
      increases in cAMP in porcine coronary artery myocytes. There are two D(1)-like
      receptors (R), D(1)R and D(5)R. We hypothesize that the specific D(1)-like
      receptor involved in BK(Ca) channel activation in human coronary artery smooth
      muscle cells (HCASMCs) is the D(5)R and that activation occurs via cAMP cross
      activation of cGMP-dependent protein kinase (PKG), rather than cAMP-dependent
      protein kinase (PKA). The effects of D(1)-like receptor agonists and antagonists
      on BK(Ca) channel opening in HCASMCs were examined in the presence and absence of
      PKG/PKA inhibition by cell-attached patch clamp. In the absence of commercially
      available ligands specific for D(1)R or D(5)R, D(1)R or D(5)R protein was down
      regulated by transfecting HCASMCs with human D(1)R or D(5)R antisense
      oligonucleotides, respectively: cells transfected with scrambled oligonucleotides
      and nontransfected HCASMCs served as controls. The predominant ion channel
      conducting outward currents in nontransfected HCASMCs was identified as the large
      conductance, calcium- and voltage-activated potassium (BK(Ca)) channel, which was
      activated by D(1)-like receptor agonists despite PKA inhibition with (9R,10S,12S)
      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 (KT 5720)
      (300 nM), but was abolished by inhibiting PKG with 9-methoxy-9-methoxycarbonyl-8
      methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b-11a-triazadibenzo(a,g)
      cycloocta(cde)-trinden-1-one (KT 5823) (300 nM). D(1)-like receptor agonists
      activated BK(Ca) channels in all transfected cells except those transfected with
      D(5)R antisense oligonucleotides. Thus, the dopamine (D(1)-like) receptor
      mediates activation of BK(Ca) channels in HCASMCs by D(5)R, not D(1)R, and via
      PKG, not PKA. This is the first report of differential D(1)-like receptor
      regulation of vascular smooth muscle function in human cells.

PMID- 19864618
TI  - Dysopsonin activity of serum DNA-binding proteins favorable for gene delivery.
AB  - Naked DNA is regarded as the safest and simplest method of gene delivery.
      However, normally intravenously injected naked plasmid DNA is rapidly eliminated
      from the blood. It has been hypothesized that opsonins, a category of serum DNA
      binding proteins (SDBPs), label the injected plasmid DNA as foreign so that it
      may be recognized and rapidly removed from the bloodstream by liver
      nonparenchymal cells. Contrary to the hypothesis, our data indicate that some
      SDBPs across multiple species may have important dysopsonin properties, acting to
      reduce liver uptake. Formation of SDBP and DNA complexes was observed by agarose
      gel electrophoresis. An in vivo study involving hepatic artery and portal vein
      occlusion in a mouse model confirmed the activity of serum diminishing liver
      uptake of DNA. Data using hydrodynamic gene transfer in the mouse liver and in
      situ transfection in the mouse lung revealed that serum proteins bound to DNA do
      not affect the biological activity of the plasmid DNA. We have identified several
      SDBPs with potential dysopsonin properties. The SDBPs with dysopsonin properties
      and DNA complexes may be further modified and ultimately be developed into a
      novel DNA carrier system favorable for systemic gene delivery.

PMID- 19864619
TI  - Letter to the editor on the new guidelines for adult critically ill patients.

PMID- 19864620
TI  - Calcium influx is sufficient to induce muscular dystrophy through a TRPC
      dependent mechanism.
AB  - Muscular dystrophy is a general term encompassing muscle disorders that cause
      weakness and wasting, typically leading to premature death. Membrane instability,
      as a result of a genetic disruption within the dystrophin-glycoprotein complex
      (DGC), is thought to induce myofiber degeneration, although the downstream
      mechanism whereby membrane fragility leads to disease remains controversial. One
      potential mechanism that has yet to be definitively proven in vivo is that
      unregulated calcium influx initiates disease in dystrophic myofibers. Here we
      demonstrate that calcium itself is sufficient to cause a dystrophic phenotype in
      skeletal muscle independent of membrane fragility. For example, overexpression of
      transient receptor potential canonical 3 (TRPC3) and the associated increase in
      calcium influx resulted in a phenotype of muscular dystrophy nearly identical to
      that observed in DGC-lacking dystrophic disease models, including a highly
      similar molecular signature of gene expression changes. Furthermore, transgene
      mediated inhibition of TRPC channels in mice dramatically reduced calcium influx
      and dystrophic disease manifestations associated with the mdx mutation
      (dystrophin gene) and deletion of the delta-sarcoglycan (Scgd) gene. These
      results demonstrate that calcium itself is sufficient to induce muscular
      dystrophy in vivo, and that TRPC channels are key disease initiators downstream
      of the unstable membrane that characterizes many types of muscular dystrophy.

PMID- 19864621
TI  - Contemporary Arctic change: a paleoclimate deja vu?

PMID- 19864622
TI  - Chemical reversal of the RNA gain of function in myotonic dystrophy.

PMID- 19864623
TI  - Fat location defines sensation.

PMID- 19864624
TI  - Molecular basis for insulin fibril assembly.
AB  - In the rare medical condition termed injection amyloidosis, extracellular fibrils
      of insulin are observed. We found that the segment of the insulin B-chain with
      sequence LVEALYL is the smallest segment that both nucleates and inhibits the
      fibrillation of full-length insulin in a molar ratio-dependent manner, suggesting
      that this segment is central to the cross-beta spine of the insulin fibril. In
      isolation from the rest of the protein, LVEALYL forms microcrystalline aggregates
      with fibrillar morphology, the structure of which we determined to 1 A
      resolution. The LVEALYL segments are stacked into pairs of tightly interdigitated
      beta-sheets, each pair displaying the dry steric zipper interface typical of
      amyloid-like fibrils. This structure leads to a model for fibrils of human
      insulin consistent with electron microscopic, x-ray fiber diffraction, and
      biochemical studies.

PMID- 19864625
TI  - Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST
      2/CD317 by intracellular sequestration.
AB  - Tetherin is an IFN-inducible restriction factor that inhibits HIV-1 particle
      release in the absence of the HIV-1 countermeasure, viral protein U (Vpu).
      Although ubiquitous in HIV-1 and simian immunodeficiency viruses from
      chimpanzees, greater spot nosed monkeys, mustached monkeys, and Mona monkeys,
      other primate lentiviruses do not encode a Vpu protein. Here we demonstrate that
      SIV from Tantalus monkeys (SIVtan) encodes an envelope glycoprotein (SIVtan Env)
      able to counteract tetherin from Tantalus monkeys, rhesus monkeys, sooty
      mangabeys, and humans, but not from pigs. We show that sensitivity to Vpu but not
      SIVtan Env can be transferred with the human tetherin transmembrane region. We
      also identify a mutation in the tetherin extracellular domain, which almost
      completely abolishes sensitivity of human tetherin to SIVtan Env without
      compromising antiviral activity or sensitivity to Vpu. SIVtan Env expression
      results in a reduction of surface tetherin, as well as reduction in tetherin co
      localization with mature surface-associated virus. Immuno-electron microscopy
      reveals co-localization of SIVtan Env with tetherin in intracellular tubulo
      vesicular structures, suggesting that tetherin is sequestered away from budding
      virions at the cell surface. Along with HIV-1 Vpu and SIV Nef, envelope
      glycoprotein is the third and most broadly active lentiviral-encoded tetherin
      countermeasure to be described. Our observations emphasize the importance of
      tetherin in protecting mammals against viral infection and suggest that HIV-1 Vpu
      inhibitors may select active envelope mutants.

PMID- 19864626
TI  - A [Cu2O]2+ core in Cu-ZSM-5, the active site in the oxidation of methane to
      methanol.
AB  - Driven by the depletion of crude oil, the direct oxidation of methane to methanol
      has been of considerable interest. Promising low-temperature activity of an
      oxygen-activated zeolite, Cu-ZSM-5, has recently been reported in this selective
      oxidation and the active site in this reaction correlates with an absorption
      feature at 22,700 cm(-1). In the present study, this absorption band is used to
      selectively resonance enhance Raman vibrations of this active site. (18)O(2)
      labeling experiments allow definitive assignment of the observed vibrations and
      exclude all previously characterized copper-oxygen species for the active site.
      In combination with DFT and normal coordinate analysis calculations, the oxygen
      activated Cu core is uniquely defined as a bent mono-(mu-oxo)dicupric site.
      Spectroscopically validated electronic structure calculations show polarization
      of the low-lying singly-occupied molecular orbital of the [Cu(2)O](2+) core,
      which is directed into the zeolite channel, upon approach of CH(4). This induces
      significant oxyl character into the bridging O atom leading to a low transition
      state energy consistent with experiment and explains why the bent mono-(mu
      oxo)dicupric core is highly activated for H atom abstraction from CH(4). The
      oxygen intermediate of Cu-ZSM-5 is now the most well defined species active in
      the methane monooxygenase reaction.

PMID- 19864627
TI  - Regulation of NF-kappaB activity through lysine monomethylation of p65.
AB  - NF-kappaB is a key activator of inflammatory and immune responses with important
      pathological roles in cancer, heart disease, and autoimmune diseases.
      Transcriptional activity of NF-kappaB is regulated by different posttranslational
      modifications. Here, we report a novel mechanism of NF-kappaB regulation through
      lysine monomethylation by SET9 methyltransferase. Set9 specifically methylates
      p65 at lysine 37. Both TNFalpha and IL-1beta treatments induced methylation of
      p65. Methylated p65 is restricted to the nucleus and this modification regulates
      the promoter binding of p65. Moreover, Set9 mediated methylation of p65 is
      required for the expression of a subset of NF-kappaB target genes in response to
      TNFalpha stimulation.

PMID- 19864628
TI  - A protein microarray-based analysis of S-nitrosylation.
AB  - The ubiquitous cellular influence of nitric oxide (NO) is exerted substantially
      through protein S-nitrosylation. Whereas NO is highly promiscuous, physiological
      S-nitrosylation is typically restricted to one or very few Cys residue(s) in
      target proteins. The molecular basis for this specificity may derive from
      properties of the target protein, the S-nitrosylating species, or both. Here, we
      describe a protein microarray-based approach to investigate determinants of S
      nitrosylation by biologically relevant low-mass S-nitrosothiols (SNOs). We
      identify large sets of yeast and human target proteins, among which those with
      active-site Cys thiols residing at N termini of alpha-helices or within catalytic
      loops were particularly prominent. However, S-nitrosylation varied substantially
      even within these families of proteins (e.g., papain-related Cys-dependent
      hydrolases and rhodanese/Cdc25 phosphatases), suggesting that neither secondary
      structure nor intrinsic nucleophilicity of Cys thiols was sufficient to explain
      specificity. Further analyses revealed a substantial influence of NO-donor
      stereochemistry and structure on efficiency of S-nitrosylation as well as an
      unanticipated and important role for allosteric effectors. Thus, high-throughput
      screening and unbiased proteome coverage reveal multifactorial determinants of S
      nitrosylation (which may be overlooked in alternative proteomic analyses), and
      support the idea that target specificity can be achieved through rational design
      of S-nitrosothiols.

PMID- 19864629
TI  - Emergent gene order in a model of modular polyketide synthases.
AB  - Polyketides are a class of biologically active heteropolymers produced by
      assembly line-like multiprotein complexes of modular polyketide synthases (PKS).
      The polyketide product is encoded in the order of the PKS proteins in the
      assembly line, suggesting that polyketide diversity derives from combinatorial
      rearrangement of these PKS complexes. Remarkably, the order of PKS genes on the
      chromosome follows the order of PKS proteins in the assembly line: This fact is
      commonly referred to as "collinearity". Here we propose an evolutionary origin
      for collinearity and demonstrate the mechanism by using a computational model of
      PKS evolution in a population. Assuming continuous evolutionary pressure for
      novel polyketides, and that new polyketide pathways are formed by horizontal
      transfer/recombination of PKS-encoding DNA, we demonstrate the existence of a
      broad range of parameters for which collinearity emerges spontaneously.
      Collinearity confers no fitness advantage in our model; it is established and
      maintained through a "secondary selection" mechanism, as a trait which increases
      the probability of forming long, novel PKS complexes through recombination.
      Consequently, collinearity hitchhikes on the successful genotypes which
      periodically sweep through the evolving population. In addition to computer
      simulation of a simplified model of PKS evolution, we provide a mathematical
      framework describing the secondary selection mechanism, which generalizes beyond
      the context of the present model.

PMID- 19864630
TI  - Tug-of-war between dissimilar teams of microtubule motors regulates transport and
      fission of endosomes.
AB  - Intracellular transport is interspersed with frequent reversals in direction due
      to the presence of opposing kinesin and dynein motors on organelles that are
      carried as cargo. The cause and the mechanism of reversals are unknown, but are a
      key to understanding how cargos are delivered in a regulated manner to specific
      cellular locations. Unlike established single-motor biophysical assays, this
      problem requires understanding of the cooperative behavior of multiple
      interacting motors. Here we present measurements inside live Dictyostelium cells,
      in a cell extract and with purified motors to quantify such an ensemble function
      of motors. We show through precise motion analysis that reversals during endosome
      motion are caused by a tug-of-war between kinesin and dynein. Further, we use a
      combination of optical trap-based force measurements and Monte Carlo simulations
      to make the surprising discovery that endosome transport uses many (approximately
      four to eight) weak and detachment-prone dyneins in a tug-of-war against a single
      strong and tenacious kinesin. We elucidate how this clever choice of dissimilar
      motors and motor teams achieves net transport together with endosome fission,
      both of which are important in controlling the balance of endocytic sorting. To
      the best of our knowledge, this is a unique demonstration that dynein and kinesin
      function differently at the molecular level inside cells and of how this
      difference is used in a specific cellular process, namely endosome biogenesis.
      Our work may provide a platform to understand intracellular transport of a
      variety of organelles in terms of measurable quantities.

PMID- 19864631
TI  - Simultaneous prediction of protein folding and docking at high resolution.
AB  - Interleaved dimers and higher order symmetric oligomers are ubiquitous in biology
      but present a challenge to de novo structure prediction methodology: The
      structure adopted by a monomer can be stabilized largely by interactions with
      other monomers and hence not the lowest energy state of a single chain. Building
      on the Rosetta framework, we present a general method to simultaneously model the
      folding and docking of multiple-chain interleaved homo-oligomers. For more than a
      third of the cases in a benchmark set of interleaved homo-oligomers, the method
      generates near-native models of large alpha-helical bundles, interlocking beta
      sandwiches, and interleaved alpha/beta motifs with an accuracy high enough for
      molecular replacement based phasing. With the incorporation of NMR chemical shift
      information, accurate models can be obtained consistently for symmetric complexes
      with as many as 192 total amino acids; a blind prediction was within 1 A rmsd of
      the traditionally determined NMR structure, and fit independently collected RDC
      data equally well. Together, these results show that the Rosetta "fold-and-dock"
      protocol can produce models of homo-oligomeric complexes with near-atomic-level
      accuracy and should be useful for crystallographic phasing and the rapid
      determination of the structures of multimers with limited NMR information.

PMID- 19864632
TI  - Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal
      immunization.
AB  - Intradermal immunization using microfabricated needles represents a potentially
      powerful technology, which can enhance immune responses and provide antigen
      sparing. Solid vaccine formulations, which can be coated onto microneedle patches
      suitable for simple administration, can also potentially offer improved shelf
      life. However the approach is not fully compatible with many vaccine adjuvants
      including alum, the most common adjuvant used in the vaccine market globally.
      Here, we introduce a polyphosphazene immuno adjuvant as a biologically potent and
      synergistic constituent of microneedle-based intradermal immunization technology.
      Poly[di(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine
      adjuvant and as a key microfabrication material. When used as part of an
      intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates
      superior activity in pigs compared to intramascular administration and
      significant antigen sparing potential. It also accelerates the microneedle
      fabrication process and reduces its dependence on the use of surfactants. In this
      way, PCPP-coated microneedles may enable effective intradermal vaccination from
      an adjuvanted patch delivery system.

PMID- 19864634
TI  - Epilepsy and aggression: proceed with caution.

PMID- 19864633
TI  - Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the
      aversive effects of stress and reinstates drug seeking.
AB  - Although stress has profound effects on motivated behavior, the underlying
      mechanisms responsible are incompletely understood. In this study we elucidate a
      functional pathway in mouse brain that encodes the aversive effects of stress and
      mediates stress-induced reinstatement of cocaine place preference (CPP).
      Activation of the dynorphin/kappa opioid receptor (KOR) system by either repeated
      stress or agonist produces conditioned place aversion (CPA). Because KOR
      inhibition of dopamine release in the mesolimbic pathway has been proposed to
      mediate the dysphoria underlying this response, we tested dopamine-deficient mice
      in this study and found that KOR agonist in these mice still produced CPA.
      However, inactivation of serotonergic KORs by injection of the KOR antagonist
      norBNI into the dorsal raphe nucleus (DRN), blocked aversive responses to the KOR
      agonist U50,488 and blocked stress-induced reinstatement of CPP. KOR knockout
      (KO) mice did not develop CPA to U50,488; however, lentiviral re-expression of
      KOR in the DRN of KOR KO mice restored place aversion. In contrast, lentiviral
      expression in DRN of a mutated form of KOR that fails to activate p38 MAPK
      required for KOR-dependent aversion, did not restore place aversion. DRN
      serotonergic neurons project broadly throughout the brain, but the inactivation
      of KOR in the nucleus accumbens (NAc) coupled with viral re-expression in the DRN
      of KOR KO mice demonstrated that aversion was encoded by a DRN to NAc projection.
      These results suggest that the adverse effects of stress may converge on the
      serotonergic system and offers an approach to controlling stress-induced
      dysphoria and relapse.

PMID- 19864635
TI  - Can rehabilitation help ataxia?

PMID- 19864637
TI  - Re: Antitumor efficacy testing in rodents.

PMID- 19864636
TI  - Intensive coordinative training improves motor performance in degenerative
      cerebellar disease.
AB  - OBJECTIVES: The cerebellum is known to play a strong functional role in both
      motor control and motor learning. Hence, the benefit of physiotherapeutic
      training remains controversial for patients with cerebellar degeneration. In this
      study, we examined the effectiveness of a 4-week intensive coordinative training
      for 16 patients with progressive ataxia due to cerebellar degeneration (n = 10)
      or degeneration of afferent pathways (n = 6). METHODS: Effects were assessed by
      clinical ataxia rating scales, individual goal attainment scores, and
      quantitative movement analysis. Four assessments were performed: 8 weeks before,
      immediately before, directly after, and 8 weeks after training. To control for
      variability in disease progression, we used an intraindividual control design,
      where performance changes with and without training were compared. RESULTS:
      Significant improvements in motor performance and reduction of ataxia symptoms
      were observed in clinical scores after training and were sustained at follow-up
      assessment. Patients with predominant cerebellar ataxia revealed more distinct
      improvement than patients with afferent ataxia in several aspects of gait like
      velocity, lateral sway, and intralimb coordination. Consistently, in patients
      with cerebellar but without afferent ataxia, the regulation of balance in static
      and dynamic balance tasks improved significantly. CONCLUSION: In patients with
      cerebellar ataxia, coordinative training improves motor performance and reduces
      ataxia symptoms, enabling them to achieve personally meaningful goals in everyday
      life. Training effects were more distinct for patients whose afferent pathways
      were not affected. For both groups, continuous training seems crucial for
      stabilizing improvements and should become standard of care. LEVEL OF EVIDENCE:
      This study provides Class III evidence that coordinative training improves motor
      performance and reduces ataxia symptoms in patients with progressive cerebellar
      ataxia.

PMID- 19864638
TI  - Re: Clinical factors associated with Merkel cell polyomavirus infection in Merkel
      cell carcinoma.

PMID- 19864639
TI  - Adipose tissue infiltration in skeletal muscle of healthy elderly men:
      relationships with body composition, insulin resistance, and inflammation at the
      systemic and tissue level.
AB  - BACKGROUND: Association between inflammatory markers and intermuscular adipose
      tissue (IMAT) has been reported. We hypothesized that subclinical inflammation of
      adipose tissue surrounding and infiltrating muscle could be related to the
      metabolic and functional abnormalities of the "aging muscle." METHODS: In 20
      healthy elderly men undergoing elective vertebral surgery, IMAT within erector
      spinae was evaluated by magnetic resonance imaging and body composition by dual
      energy x-ray absorptiometry. Fasting glucose, insulin, high-sensitive C-reactive
      protein (hs-CRP), leptin, adiponectin, and interleukin 6 (IL-6) were measured,
      and insulin resistance was estimated by homeostasis model assessment (HOMA)
      index. In subcutaneous adipose tissue (SAT) biopsies near the erector spinae,
      quantification of gene expression was performed. RESULTS: IMAT showed a
      significant association with body mass index and total and regional body fat,
      even after adjustment for age. Insulin, HOMA, and leptin were significantly
      correlated with IMAT, whereas hs-CRP presented an association of borderline
      significance. IL-6 expression in SAT was significantly associated with IMAT; IL-6
      messenger RNA (mRNA) was negatively associated with adiponectin and peroxisome
      proliferator-activated receptor gamma expression. In multivariate regression
      analysis, 68% of IMAT variance was explained by fat mass and age, independent of
      waist circumference, leptin, HOMA, and IL-6 mRNA. CONCLUSION: IMAT was primarily
      related to age and total body adiposity; subclinical inflammation in fat
      significantly contributes to IMAT.

PMID- 19864640
TI  - Neuroticism in adolescence and cognitive function in midlife in the British 1946
      birth cohort: The HALCyon program.
AB  - We examined whether higher levels of neuroticism in adolescence were associated
      with poorer cognitive function in midlife in 2,071 members of the British 1946
      birth cohort. Higher neuroticism at age 13 was associated with poorer performance
      on tests of verbal ability, verbal fluency, and verbal memory at age 53 in sex
      adjusted analyses. However, higher neuroticism was also associated with poorer
      cognitive performance at age 8. After adjustment for childhood cognition or
      educational attainment, the associations between neuroticism at age 13 and
      midlife cognition ceased to be statistically significant. The link between
      neuroticism and subsequent cognitive ability may be a reflection of a long
      standing correlation between the stable aspects of these traits since childhood,
      but further measurements of both traits are needed to confirm this.

PMID- 19864641
TI  - MAP kinase phosphatase-1 protects against inflammatory bone loss.
AB  - The mitogen-activated protein (MAP) kinase phosphatase (MKP) family plays an
      important function in regulating the pro-inflammatory cytokines by deactivating
      MAP kinases. MKP-1 is essential for the dephosphorylation of p38 MAP kinase that
      regulates expression of IL-6, TNF-alpha, and IL-1 beta. We hypothesized that MKP
      1 regulates inflammatory bone loss in experimental periodontitis. Wild-type and
      Mkp-1(-/-) mice received A. actinomycetemcomitans LPS injection in the palatal
      region or PBS control 3 times/wk for 30 days. Mice were killed, and maxillae were
      assessed by microcomputed tomography, histological analysis, and TRAP staining
      for measurement of bone loss, extent of inflammation, and degree of
      osteoclastogenesis. Results indicated that, in LPS-injected Mkp-1(-/-) mice,
      significantly greater bone loss occurred with more inflammatory infiltrate and a
      significant increase in osteoclastogenesis compared with Mkp-1(-/-) control sites
      or either wild-type group. Analysis of these data indicates that MKP-1 plays a
      key role in the regulation of inflammatory bone loss.

PMID- 19864642
TI  - Alpha-defensins secreted by dysplastic granulocytes inhibit the differentiation
      of monocytes in chronic myelomonocytic leukemia.
AB  - Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder that
      occurs in elderly patients. One of the main diagnostic criteria is the
      accumulation of heterogeneous monocytes in the peripheral blood. We further
      explored this cellular heterogeneity and observed that part of the leukemic clone
      in the peripheral blood was made of immature dysplastic granulocytes with a CD14(
      )/CD24(+) phenotype. The proteome profile of these cells is dramatically distinct
      from that of CD14(+)/CD24(-) monocytes from CMML patients or healthy donors. More
      specifically, CD14(-)/CD24(+) CMML cells synthesize and secrete large amounts of
      alpha-defensin 1-3 (HNP1-3). Recombinant HNPs inhibit macrophage colony
      stimulating factor (M-CSF)-driven differentiation of human peripheral blood
      monocytes into macrophages. Using transwell, antibody-mediated depletion, suramin
      inhibition of purinergic receptors, and competitive experiments with uridine
      diphosphate (UDP)/uridine triphosphate (UTP), we demonstrate that HNP1-3 secreted
      by CD14(-)/CD24(+) cells inhibit M-CSF-induced differentiation of CD14(+)/CD24(-)
      cells at least in part through P2Y6, a receptor involved in macrophage
      differentiation. Altogether, these observations suggest that a population of
      immature dysplastic granulocytes contributes to the CMML phenotype through
      production of alpha-defensins HNP1-3 that suppress the differentiation
      capabilities of monocytes.

PMID- 19864643
TI  - Mta3-NuRD complex is a master regulator for initiation of primitive hematopoiesis
      in vertebrate embryos.
AB  - Metastasis-associated antigens 1/2/3 (Mta1/2/3) are components of nucleosome
      remodeling and deacetylase (NuRD) complexes and have been found to play roles in
      embryonic development and homeostasis. However, their functions in primitive
      hematopoiesis are unknown. In this study, we demonstrate that knockdown of mta3
      by antisense morpholinos abolishes primitive hematopoietic lineages and causes
      abnormal angiogenesis in zebrafish embryos. However, the expression of the
      pronephric duct and paraxial mesoderm markers is unaltered and the specification
      of angioblasts is unaffected in mta3 morphants. The results suggest that mta3 is
      specifically required for primitive hematopoiesis. Furthermore, inhibition of
      deacetylase activity with the inhibitors valproic acid (VPA) or trichostatin A
      (TSA) in zebrafish embryos completely blocks primitive hematopoiesis, resulting
      in hematopoietic defects almost identical to those seen in mta3 morphants.
      Importantly, overexpression of scl or scl and lmo2, 2 master genes for primitive
      hematopoiesis, is able to overturn effects of mta3 knockdown or VPA/TSA
      treatment; and overexpression of mta3, and human MBD3 or HDAC1, 2 other
      components of NuRD complex, enhances the expression of scl and lmo2 in the
      posterior lateral plate mesoderm during early primitive hematopoiesis. We
      conclude that Mta3-NuRD complex is essential for the initiation of primitive
      hematopoiesis. Thus, our findings provide new insight into the regulatory
      hierarchy of primitive hematopoiesis in vertebrates.

PMID- 19864646
TI  - Communal responsibility for health care--the example of benefit assessment in
      Germany.

PMID- 19864644
TI  - W41/W41 blastocyst complementation: a system for genetic modeling of
      hematopoiesis.
AB  - We report a rapid and highly efficient approach to generate mice in which the
      hematopoietic system is derived from embryonic stem (ES) cells. We show that ES
      cells injected into blastocysts from the c-kit-deficient W(41)/W(41) mouse strain
      have a clear advantage over the W(41)/W(41) blastocyst-derived inner cell mass
      cells in founding the hematopoietic system. Fetal liver hematopoietic stem cells
      from W(41)/W(41) blastocyst complementation embryos can be transplanted to
      establish large cohorts of bone marrow chimeras with hematopoiesis of practically
      pure ES-cell origin. Using ES cells with site-directed modifications, we show how
      this system can be used to drive inducible transgene expression in hematopoietic
      cells in a robust and reliable manner both in vitro and in vivo. The approach
      avoids the cost and time constraints associated with the creation of standard
      transgenic mouse strains while taking advantage of the sophisticated site
      directed manipulations that are possible in ES cells.

PMID- 19864645
TI  - Epigenetic regulation of dendritic cell differentiation and function by oxidized
      phospholipids.
AB  - Dendritic cells (DCs) are the key cell type in the regulation of an adaptive
      immune response. Under inflammatory conditions monocytes can give rise to
      immunostimulatory DCs, depending on microenvironmental stimuli. Here we show that
      oxidized phospholipids (Ox-Pls), which are generated during inflammatory
      reactions, dysregulate the differentiation of DCs. DCs generated in the presence
      of Ox-Pls up-regulated the typical DC marker DC-SIGN but did not express CD1a,
      CD1b, and CD1c. These DCs generated in the presence of Ox-Pls had a substantially
      diminished T cell-stimulating capacity after stimulation with Toll-like receptor
      ligands. Toll-like receptor ligand-induced production of interleukin-12 also was
      strongly diminished, whereas induction of CD83 was not altered. In addition, we
      found that Ox-Pls strongly inhibit inflammatory stimuli-induced phosphorylation
      of histone H3, a key step of interleukin-12 production, yet leaving activation of
      nuclear factor-kappaB unaltered. Taken together, Ox-Pls present during
      differentiation yielded DCs with a reduced capacity to become immunostimulatory
      mature DCs. Furthermore, the presence of Ox-Pls blocked histone modifications
      required for full activation of DCs. Therefore, inflammation-derived Ox-Pls
      control DC functions in part by epigenetic mechanisms.

PMID- 19864647
TI  - Which medicine, which America?

PMID- 19864648
TI  - Ensuring progress in primary care--what can health care reform realistically
      accomplish?

PMID- 19864649
TI  - Primary care and accountable care--two essential elements of delivery-system
      reform.

PMID- 19864653
TI  - Vascular risk factors and dementia revisited.

PMID- 19864654
TI  - Mouths and brains. Could oral infection be a risk factor for dementia?

PMID- 19864655
TI  - CSF shunt failure: an ongoing epidemic?

PMID- 19864656
TI  - Inclusion body myositis: old and new concepts.
AB  - Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy
      occurring in patients over the age of 50 years and probably accounts for about
      30% of all inflammatory myopathies. Muscle biopsy characteristically reveals
      endomysial inflammation, small groups of atrophic fibres, eosinophilic
      cytoplasmic inclusions and muscle fibres with one or more rimmed vacuoles.
      However, any given biopsy may lack these histopathological abnormalities; the
      clinical examination is often the key to diagnosis. Early and often asymmetrical
      weakness and atrophy of the quadriceps and flexor forearm muscles (ie, wrist and
      finger flexors) are the clinical hallmarks of IBM. The pathogenesis of IBM is
      unknown. It may be autoimmune inflammatory myopathy or a primary degenerative
      myopathy with a secondary inflammatory. A prevailing theory is that there is an
      overproduction of beta-amyloid precursor protein in muscle fibres that is somehow
      cleaved into abnormal beta-amyloid, and the accumulation of the latter is somehow
      toxic to muscle fibres. However, there are many problems with this theory and
      more work needs to be done. Unfortunately, IBM is generally refractory to
      therapy. Further research into the pathogenesis, along with both preliminary
      small pilot trials and larger double blind, placebo controlled efficacy trials,
      are needed to make progress in our understanding and therapeutic approach for
      this disorder.

PMID- 19864657
TI  - Neurological picture. From carotid atherosclerosis plaque to brain in a single
      routine clinical MRI study at high field.

PMID- 19864658
TI  - Neurological picture. Paget's disease.

PMID- 19864659
TI  - Combined risk effects of IDE and NEP gene variants on Alzheimer disease.
AB  - Polymorphisms in genes encoding amyloid beta-peptide (A beta)-degrading enzymes
      neprilysin (NEP) and insulin-degrading enzyme (IDE) individually affect the
      susceptibility to Alzheimer disease (AD) among the Finnish population. Here we
      show that a combination of risk genotypes for NEP and IDE genes leads to a higher
      susceptibility to AD. Individuals with the combination of risk genotypes for NEP
      and IDE conferred a threefold higher susceptibility to AD when compared with
      individuals not carrying these genotypes. Although no significant interaction was
      observed between NEP and IDE genes, these data suggest that NEP and IDE exhibit
      an additive risk effect in AD.

PMID- 19864660
TI  - Risk factors for progressive supranuclear palsy: a case-control study in France.
AB  - BACKGROUND: The risk factors of progressive supranuclear palsy (PSP), a rare but
      severe Parkinsonian syndrome, are poorly known. OBJECTIVE: To study the risk
      factors of PSP in a case control study among French patients. METHOD: The study
      was conducted between April 2000 and December 2003. Cases were in- or outpatients
      of five large hospitals and fulfilled the Golbe criteria. Controls were relatives
      of patients from the same hospitals, free of Parkinsonian syndrome and dementia,
      and matched to cases for age, gender and living area. Data on demographic
      characteristics, occupation history, diet habits, anti-inflammatory drugs use,
      alcohol consumption, smoking habits, gardening and leisure activities, and
      exposure to pesticides were collected through a face-to-face questionnaire. A
      conditional logistic regression was used to analyse matched data and estimate OR.
      RESULTS: 79 cases and 79 controls were included. Only a few comparisons were
      significant. Cases reached a lower education attainment than controls (odds ratio
      (OR) = 2.6 (1.3 to 5.3), p = 0.01). Analysis of diet habits did not show any
      major difference although cases ate meat or poultry more frequently. Conversely,
      controls ate fruits more frequently than did cases. No association was found
      between PSP and occupation, use of pesticides, gardening, alcohol consumption,
      smoking habits and anti-inflammatory agent use. CONCLUSION: In this case-control
      study, we did not find any strong environmental risk factors for PSP.

PMID- 19864661
TI  - Thoracolumbar spinal fixation for camptocormia in Parkinson's disease.
AB  - A man with early non-fluctuating Parkinson's disease developed disabling
      camptocormia. The patient was treated with posterior thoracolumbar fixation,
      which subsequently had to be augmented with anterior interbody fusion. Although
      the patient ultimately achieved excellent sagittal correction, his postoperative
      course was complicated and prolonged. Therefore, although this case demonstrates
      that spinal fixation surgery can be successful, it should probably only be
      offered after subthalamic nucleus deep brain stimulation has been unsuccessful,
      or for well motivated patients who express a strong wish for this major
      reconstructive surgery.

PMID- 19864662
TI  - Occurrence and risk factors for apathy in Parkinson disease: a 4-year prospective
      longitudinal study.
AB  - BACKGROUND: Apathy is a common but under-recognised behavioural disorder
      associated with depression and cognitive impairment in patients with Parkinson
      disease (PD). However, the longitudinal course of apathy in PD has not been
      studied. OBJECTIVE: To examine the occurrence of and risk factors for apathy over
      time in a representative sample of patients with PD. METHODS: A sample of 139
      patients was drawn from a population-based prevalence study of PD in Rogaland
      County, Western Norway. Apathy was measured with the Neuropsychiatric Inventory,
      using a composite score >or=4 to indicate clinically significant apathy.
      Additional measurements included standardised rating scales for parkinsonism,
      depression and cognitive impairment. A follow-up evaluation was carried out in 79
      patients (78.2% of the survivors) 4 years later. RESULTS: Of the 79 patients
      included in this study, 29 patients (36.7%) had never had apathy, 11 (13.9%) had
      persistent apathy, and a further 39 (49.4%) developed apathy during follow-up. At
      follow-up, patients with apathy were more frequently depressed and demented than
      never-apathetic patients. Dementia at baseline and a more rapid decline in speech
      and axial impairment during follow-up were independent risk factors for incident
      apathy. CONCLUSIONS: Apathy is a persistent behavioural feature in PD with a high
      incidence and prevalence over time. Progression of motor signs predominantly
      mediated by non-dopaminergic systems may be a useful preclinical marker for
      incident apathy in PD.

PMID- 19864663
TI  - TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but
      absence of copy number variation.
AB  - BACKGROUND: Mutations in the gene encoding TDP-43 have been identified in both
      familial and sporadic amyotrophic lateral sclerosis (ALS). METHODS: A mutation
      screen and copy number analysis in a motor neuron disease clinic cohort was
      conducted to characterise the genetic contribution of TARDBP. RESULTS: A novel
      missense mutation in a highly conserved region of TDP-43 was identified in a
      patient with sporadic ALS. The mutation is in close vicinity to previously
      identified changes. Copy number variation abnormalities were not detected.
      CONCLUSIONS: The findings stress the importance of TDP-43 in the pathogenesis of
      sporadic ALS.

PMID- 19864664
TI  - A novel TARDBP mutation in an Australian amyotrophic lateral sclerosis kindred.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that
      causes loss of motor neurons. A pathological hallmark of ALS is the presence of
      ubiquitinated TAR DNA binding protein (TDP-43) inclusions in the cytoplasm of
      affected cells. Rare pathogenic mutations within the gene TARDBP that encode TDP
      43 were recently reported in ALS but their functional consequences are unknown.
      To further investigate the pathogenic role of TDP-43 in ALS, a mutation analysis
      of TARDBP was performed in an Australian cohort of 74 sporadic and 30 familial
      ALS cases. A novel familial ALS mutation in TDP-43 was identified that
      substitutes a highly conserved residue (G294V) and is predicted to disrupt the
      glycine rich domain in the C terminus, a region that plays a role in RNA binding
      and is required for the exon skipping activity of TDP-43.

PMID- 19864665
TI  - Episodic ataxia type 2: unusual aspects in clinical and genetic presentation.
      Special emphasis in childhood.
AB  - OBJECTIVE: To describe aspects in clinical and genetic presentation in five
      patients with episodic ataxia type 2 (EA2). METHODS: CACNA1A gene screening
      identified a mutation in three probands and in two of their children. RESULTS:
      The three probands had attacks of imbalance, associated with dizziness/vertigo
      and/or headache. Two of them had independent migraine attacks. Interictal
      oculomotor examination revealed a gaze evoked nystagmus and central oculomotor
      signs. Two probands had a history of strabismus. All responded well to
      acetazolamide. Two children were found to have both clinical and genetic
      abnormalities. At 23 months, one child started to have short attacks of imbalance
      mimicking benign paroxysmal vertigo of childhood. Then, the frequency and
      duration of his attacks increased and some were associated with headache. The
      other child developed permanent imbalance with falls at the age of 2 years,
      strabismus, hyperactivity and slight to moderate cognitive deficiency. When aged
      10 years, this was further complicated by episodic ataxia. Genetic analysis
      revealed three novel mutations in the calcium channel gene CACNA1A (chromosome
      19p13). The two children had the same genetic abnormality as their parents.
      CONCLUSION: EA2 may present with still unknown genetic mutations in adults, and
      with large and various phenotypes in children, such as short attacks of imbalance
      or permanent imbalance, cognitive deficiency, and possibly strabismus and
      hyperactivity.

PMID- 19864666
TI  - Strong association between myotonic dystrophy type 2 and autoimmune diseases.
AB  - BACKGROUND: Myotonic dystrophy type 2 (DM2) is a dominantly inherited multisystem
      disorder, characterised by progressive proximal weakness, myotonia, cataracts and
      cardiac conduction abnormalities. Our clinical impression of an association
      between DM2 and autoimmune diseases or autoantibody formation has not been
      published previously. OBJECTIVE: The aim of the present study was to investigate
      the frequency of autoimmune diseases and serum autoantibodies in patients with
      DM2 compared with patients with adult onset myotonic dystrophy type 1 (DM1).
      METHODS: 28 genetically proven Dutch DM2 patients participated in the study and
      were compared with 51 age and sex matched adult onset DM1 patients. As the
      primary outcome measure, the presence of an autoantibody or autoreactive T cell
      associated autoimmune disorder was assessed. As a secondary outcome measure, the
      presence of autoantibodies in serum (nuclear and non-nuclear antibodies) was
      assessed in all patients. RESULTS: The frequency of autoimmune diseases (21% vs
      2%) and the frequency of autoantibodies (25% vs 2%) were both significantly
      (p<0.01) higher in DM2 patients compared with DM1 patients. Data on DM1 patients
      were comparable with the general population. Results were not confounded by
      smoking, medication use, familial clustering, age or sex. CONCLUSION: The results
      provide new insight into the clinical picture of DM2. In addition, possible
      explanations for the association between DM2 and autoimmune diseases are
      proposed.

PMID- 19864667
TI  - Coexistence of chronic inflammatory demyelinating polyneuropathy and
      camptocormia.

PMID- 19864668
TI  - Corticobasal syndrome associated with a novel 1048_1049insG progranulin mutation.

PMID- 19864669
TI  - Treatment of musical hallucinosis with acetylcholinesterase inhibitors.

PMID- 19864670
TI  - Images in clinical medicine. A swinging heart.

PMID- 19864671
TI  - Implementing evidence-based health policy in Washington State.

PMID- 19864672
TI  - A homozygous CARD9 mutation in a family with susceptibility to fungal infections.
AB  - BACKGROUND: Chronic mucocutaneous candidiasis may be manifested as a primary
      immunodeficiency characterized by persistent or recurrent infections of the
      mucosa or the skin with candida species. Most cases are sporadic, but both
      autosomal dominant inheritance and autosomal recessive inheritance have been
      described. METHODS: We performed genetic studies in 36 members of a large,
      consanguineous five-generation family, in which 4 members had recurrent fungal
      infections and an additional 3 members died during adolescence, 2 after invasive
      infection of the brain with candida species. All 36 family members were enrolled
      in the study, and 22 had blood samples taken for DNA analysis. Homozygosity
      mapping was used to locate the mutated gene. In the 4 affected family members
      (patients) and the 18 unaffected members we sequenced CARD9, the gene encoding
      the caspase recruitment domain-containing protein 9, carried out T-cell
      phenotyping, and performed functional studies, with the use of either leukocytes
      from the patients or a reconstituted murine model of the genetic defect. RESULTS:
      We found linkage (lod score, 3.6) to a genomic interval on chromosome 9q,
      including CARD9. All four patients had a homozygous point mutation in CARD9,
      resulting in a premature termination codon (Q295X). Healthy family members had
      wild-type expression of the CARD9 protein; the four patients lacked wild-type
      expression, which was associated with low numbers of Th17 cells (helper T cells
      producing interleukin-17). Functional studies based on genetic reconstitution of
      myeloid cells from Card9(-/-) mice showed that the Q295X mutation impairs innate
      signaling from the antifungal pattern-recognition receptor dectin-1. CONCLUSIONS:
      An autosomal recessive form of susceptibility to chronic mucocutaneous
      candidiasis is associated with homozygous mutations in CARD9.

PMID- 19864673
TI  - Antibiotic prophylaxis and recurrent urinary tract infection in children.
AB  - BACKGROUND: Antibiotics are widely administered to children with the intention of
      preventing urinary tract infection, but adequately powered, placebo-controlled
      trials regarding efficacy are lacking. This study from four Australian centers
      examined whether low-dose, continuous oral antibiotic therapy prevents urinary
      tract infection in predisposed children. METHODS: We randomly assigned children
      under the age of 18 years who had had one or more microbiologically proven
      urinary tract infections to receive either daily trimethoprim-sulfamethoxazole
      suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram
      of body weight) or placebo for 12 months. The primary outcome was
      microbiologically confirmed symptomatic urinary tract infection. Intention-to
      treat analyses were performed with the use of time-to-event data. RESULTS: From
      December 1998 to March 2007, a total of 576 children (of 780 planned) underwent
      randomization. The median age at entry was 14 months; 64% of the patients were
      girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these
      patients), and 71% were enrolled after the first diagnosis of urinary tract
      infection. During the study, urinary tract infection developed in 36 of 288
      patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic
      group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the
      antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the
      log-rank test). In the antibiotic group, the reduction in the absolute risk of
      urinary tract infection (6 percentage points) appeared to be consistent across
      all subgroups of patients (P > or = 0.20 for all interactions). CONCLUSIONS: Long
      term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased
      number of urinary tract infections in predisposed children. The treatment effect
      appeared to be consistent but modest across subgroups. (Australian New Zealand
      Clinical Trials Registry number, ACTRN12608000470392.)

PMID- 19864674
TI  - Human dectin-1 deficiency and mucocutaneous fungal infections.
AB  - Mucocutaneous fungal infections are typically found in patients who have no known
      immune defects. We describe a family in which four women who were affected by
      either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop
      codon mutation Tyr238X in the beta-glucan receptor dectin-1. The mutated form of
      dectin-1 was poorly expressed, did not mediate beta-glucan binding, and led to
      defective production of cytokines (interleukin-17, tumor necrosis factor, and
      interleukin-6) after stimulation with beta-glucan or Candida albicans. In
      contrast, fungal phagocytosis and fungal killing were normal in the patients,
      explaining why dectin-1 deficiency was not associated with invasive fungal
      infections and highlighting the specific role of dectin-1 in human mucosal
      antifungal defense.

PMID- 19864675
TI  - Clinical practice. Postexposure prophylaxis for HIV infection.

PMID- 19864677
TI  - Images in clinical medicine. Central nervous system hemorrhage.

PMID- 19864678
TI  - Case records of the Massachusetts General Hospital. Case 34-2009. A 20-year-old
      man with sore throat, fever, and rash.

PMID- 19864676
TI  - Norovirus gastroenteritis.

PMID- 19864679
TI  - Yeast infections--human genetics on the rise.

PMID- 19864680
TI  - Antimicrobial prophylaxis for urinary tract infection in children.

PMID- 19864681
TI  - Artemisinin resistance in Plasmodium falciparum malaria.

PMID- 19864682
TI  - Peginterferon alfa-2b or alfa-2a with ribavirin for hepatitis C.

PMID- 19864683
TI  - Hearing improvement after bevacizumab for neurofibromatosis type 2.

PMID- 19864684
TI  - Death in a gene-therapy trial.

PMID- 19864685
TI  - Cumulative live-birth rates in a trial of single-embryo or double-embryo
      transfer.

PMID- 19864686
TI  - Lessons from the past decade for future health reforms.

PMID- 19864687
TI  - Painful ears and a cough.

PMID- 19864690
TI  - In vivo stoichiometry of shelterin components.
AB  - Human telomeres bind shelterin, the six-subunit protein complex that protects
      chromosome ends from the DNA damage response and regulates telomere length
      maintenance by telomerase. We used quantitative immunoblotting to determine the
      abundance and stoichiometry of the shelterin proteins in the chromatin-bound
      protein fraction of human cells. The abundance of shelterin components was
      similar in primary and transformed cells and was not correlated with telomere
      length. The duplex telomeric DNA binding factors in shelterin, TRF1 and TRF2,
      were sufficiently abundant to cover all telomeric DNA in cells with short
      telomeres. The TPP1.POT1 heterodimer was present 50-100 copies/telomere, which is
      in excess of its single-stranded telomeric DNA binding sites, indicating that
      some of the TPP1.POT1 in shelterin is not associated with the single-stranded
      telomeric DNA. TRF2 and Rap1 were present at 1:1 stoichiometry as were TPP1 and
      POT1. The abundance of TIN2 was sufficient to allow each TRF1 and TRF2 to bind to
      TIN2. Remarkably, TPP1 and POT1 were approximately 10-fold less abundant than
      their TIN2 partner in shelterin, raising the question of what limits the
      accumulation of TPP1 x POT1 at telomeres. Finally, we report that a 10-fold
      reduction in TRF2 affects the regulation of telomere length but not the
      protection of telomeres in tumor cell lines.

PMID- 19864692
TI  - Persistence of bilayered living-cell therapy donor DNA 10 months after
      application: a case report.
AB  - Bilayered living-cell therapy has been shown in clinical trials to improve the
      rate of healing diabetic and venous leg ulcerations. However, literature is
      conflicted regarding the length of time living-cell therapy persists in acute and
      chronic wounds. An otherwise healthy 48-year-old man with sepsis from extensive
      lower-extremity wounds due to ecthyma gangrenosum was admitted to the hospital.
      Initial treatment consisted of surgical debridement, broad-spectrum antibiotics,
      and stabilization in the intensive care unit. After the patient was stabilized,
      three units of living-cell therapy meshed at a 3:1 ratio were applied to the
      wounds. Both wounds were healed after 20 weeks. Ten months post grafting, the
      patient returned with a recurrent ulcer in the area of graft placement. A biopsy
      of the wound for human leukocyte antigen revealed the presence of donor DNA from
      the bilayered living-cell therapy. This case suggests that bilayered living-cell
      therapy may persist for prolonged periods in patients without underlying skin
      disease or immunosuppression. Research to explicate the mode of action and
      optimal protocols for use of living-cell therapy is warranted.

PMID- 19864691
TI  - Structural and dynamic features of the MutT protein in the recognition of
      nucleotides with the mutagenic 8-oxoguanine base.
AB  - Escherichia coli MutT hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, an event that can
      prevent the misincorporation of 8-oxoguanine opposite adenine in DNA. Of the
      several enzymes that recognize 8-oxoguanine, MutT exhibits high substrate
      specificity for 8-oxoguanine nucleotides; however, the structural basis for this
      specificity is unknown. The crystal structures of MutT in the apo and holo forms
      and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8
      oxo-dGMP plus Mn(2+), respectively, were determined. MutT strictly recognizes the
      overall conformation of 8-oxo-dGMP through a number of hydrogen bonds. This
      recognition mode revealed that 8-oxoguanine nucleotides are discriminated from
      guanine nucleotides by not only the hydrogen bond between the N7-H and Odelta
      (N119) atoms but also by the syn glycosidic conformation that 8-oxoguanine
      nucleotides prefer. Nevertheless, these discrimination factors cannot by
      themselves explain the roughly 34,000-fold difference between the affinity of
      MutT for 8-oxo-dGMP and dGMP. When the binary complex of MutT with 8-oxo-dGMP is
      compared with the ligand-free form, ordering and considerable movement of the
      flexible loops surrounding 8-oxo-dGMP in the binary complex are observed. These
      results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by
      the ligand-induced conformational change.

PMID- 19864693
TI  - A simple device for closure of a colocutaneous fistula within the laparotomy
      wound: a case report.
AB  - Colocutaneous fistulas within laparotomy wounds are rare and difficult to treat.
      Surgical repair may be contraindicated or not desired and negative pressure wound
      therapy may not be successful. A simple device made from a silicone, flexi-aid
      hand exerciser was used to close a colocutaneous fistula within the laparotomy
      wound of a 50-year old man following surgery of an esophageal carcinoma and a
      surgical history of Whipple's procedure for adenocarcinoma of the ampulla of
      Vater. His wound developed 9 days postoperatively, measured 8 cm x 3 cm x 2 cm,
      and was contaminated with fecal material. Initial efforts involving cleansing and
      the use of negative pressure wound therapy were unsuccessful and the patient
      refused additional surgery. In this patient, a silicone occlusion device, used in
      conjunction with a silver hydrofiber dressing, prevented fecal soiling and
      facilitated closure of the colocutaneous fistula and the laparotomy wound. He was
      discharged on postop day 22 and healed by postop day 64. This was the first time
      this approach was used. Studies to optimize nonsurgical management approaches of
      these complicated conditions are needed.

PMID- 19864694
TI  - Managing complex, high-output, enterocutaneous fistulas: a case study.
AB  - Gastrointestinal (GI) fistulas are an uncommon but serious complication.
      Following diagnosis, management strategies may have to be adapted frequently to
      address changes in fistula output, surrounding skin or wound condition, overall
      patient clinical and nutritional status, mobility level, and body contours.
      Following a motor vehicle accident, a 49-year-old man with a body mass index of
      36.8 and a history of multiple previous surgeries, including gastric bypass,
      experienced excessive output from a fistula within a large open abdominal wound
      measuring 45 cm x 40 cm x 5 cm. Abdominal creases and the need to protect a split
      thickness skin graft of the wound surrounding his fistula complicated wound
      management. During his prolonged 4-month hospital stay, the patient underwent
      several surgical procedures, repeated wound debridement, and various nutritional
      support interventions; a wide variety of wound and fistula management systems
      were utilized. One year after the initial trauma, the fistula was surgically
      closed. One week later, the patient died from a cardiac event. This case study
      confirms that GI fistulas increase costs of care and hospital length of stay and
      require the experience and expertise of a wide array of patient support staff
      members and clinicians.

PMID- 19864695
TI  - Acellular bovine-derived matrix used on a traumatic crush injury of the hand: a
      case study.
AB  - Wound care options that provide quality care at a reasonable cost are integral to
      limb salvage and everyday treatment approaches in patients with traumatic
      injuries and nonhealing, chronic wounds. Human skin substitutes, or bioengineered
      tissues, have been available for many years but data about the use, safety, and
      effectiveness of bovine-derived bioengineered products are limited. A 50-year old
      man was seen at the wound clinic with a failing skin graft 65 days after
      sustaining a crush injury of his dominant hand. Following the injury, the patient
      underwent amputation of the ring and little finger, a revascularization
      procedure, and an open reduction and internal fixation of the right thumb and
      long finger. Following debridement, two applications of bovine-derived
      bioengineered tissue resulted in wound closure, limb preservation, and maximum
      functional use. Use of hydrogel-soaked and petrolatum-impregnated gauze as
      secondary and tertiary dressings, respectively, was needed to help maintain
      optimal bioengineered tissue moisture levels. Additional clinical studies to
      assess the use, safety, and cost effectiveness of this treatment modality are
      warranted.

PMID- 19864696
TI  - Accurate measurement of extracellular fluid volume from the slope/intercept
      technique after bolus injection of a filtration marker.
AB  - Extracellular fluid volume (ECV) is studied infrequently. The zero-time
      distribution volume (Vd) generated in the slope-intercept technique for measuring
      the glomerular filtration rate (GFR) substantially overestimates ECV. The aim was
      to validate a new technique for measuring ECV from the slope-intercept approach.
      GFR and ECV were measured using Cr-51-EDTA and iohexol injected into opposite
      arms in 51 patients undergoing routine measurement of GFR and on 48 occasions in
      20 healthy volunteers. Blood samples were obtained bilaterally 20, 40, 60, 120,
      180 and 240 min post-injection and assayed for indicator injected
      contralaterally. Reference ECV (ECV6) was calculated from all six samples as the
      product of indicator transit time and multi-sample GFR. GFR/ECV was calculated as
      the rate constant of the exponential fitted to the last three samples (GFR/ECV3).
      Slope-intercept GFR was calculated from the last three samples using the slope
      intercept technique (GFR3). ECV (ECV3) was calculated by dividing GFR3 by
      GFR/ECV3, having corrected both for their one-compartment assumptions. ECV6(EDTA)
      correlated closely with ECV3(EDTA) (ECV3(EDTA) = 1.01.ECV6(EDTA)-0.5 L; r = 0.97;
      n = 99), but less closely with Vd (Vd = 1.17.ECV6(EDTA) + 0.7 L; r = 0.86).
      ECV6(iohexol) correlated slightly better with ECV6 (EDTA) (ECV6(EDTA) =
      0.81.ECV6(iohexol) + 3.3 L; r = 0.86) than with ECV3(EDTA) (ECV3(EDTA) =
      0.83.ECV6(iohexol) + 2.9 L; r = 0.84) and had slightly narrower 95% limits of
      agreement (-3.82 and 2.82 L versus -3.90 to 3.43 L). In conclusion, ECV can be
      measured from three samples almost as accurately as ECV from multiple samples.

PMID- 19864697
TI  - Test of the nuclear interaction model in SHIELD-HIT and comparison to energy
      distributions from GEANT4.
AB  - Monte Carlo codes are widely used to simulate dose distributions in ion
      radiotherapy. The benchmark of the implemented physical models against
      experimental data plays an important role in improving the accuracy of the
      simulations. To estimate the accuracy of the inelastic cross sections in SHIELD
      HIT, the simulated charge is compared to measured data from a Multi Layer Faraday
      Cup. In addition, the results are compared to GEANT4, which are already
      published. Furthermore, energy distributions are simulated with SHIELD-HIT07 and
      GEANT4.8.1. From a comparison of depth distributions and beam profiles of 100 and
      200 MeV protons, we estimate the level of agreement of the two codes. Nuclear
      interactions predicted by SHIELD-HIT underestimate the total amount of measured
      charge. The energy distributions from SHIELD-HIT and GEANT4 show differences
      exceeding the statistical uncertainties of 2%. Due to a difference of the Bragg
      curve of 0.5 +/- 0.3 mm on average, the mean difference in dose is 3.5% with a
      maximum deviation of 7% for the simulated cases.

PMID- 19864698
TI  - Development of a generic thresholding algorithm for the delineation of 18FDG-PET
      positive tissue: application to the comparison of three thresholding models.
AB  - An iterative generic algorithm has been developed to compare three thresholding
      models used to delineate gross tumour volume on (18)F-FDG PET images. 3D volume
      was extracted and characteristic parameters were measured. Three fitting models
      using different parameters were studied: model 1 (volume, contrast), model 2
      (contrast) and model 3 (SUV). The calibration was performed using a cylindrical
      phantom filled with hot spheres. To validate the models, two other phantoms were
      used. The calibration procedure showed a better fitting model for model 1 (R(2)
      from 0.94 to 1.00) than for model 3 (0.95) and model 2 (0.69). The validation
      study shows that model 3 yielded large volume measurement errors. Models 1 and 2
      gave close results with no significant differences. Model 2 was preferred because
      it presents less error dispersion and needs fewer characteristic parameters,
      making it easier to implement. Our results show the importance of developing a
      generic algorithm to compare the performances of fitting models objectively and
      to validate results on other phantoms than the ones used during the calibration
      process to avoid methodological biases.

PMID- 19864699
TI  - Diffusion and near-equilibrium distribution of MRI and CT contrast agents in
      articular cartilage.
AB  - Charged contrast agents have been used both in vitro and in vivo for estimation
      of the fixed charge density (FCD) in articular cartilage. In the present study,
      the effects of molecular size and charge on the diffusion and equilibrium
      distribution of several magnetic resonance imaging (MRI) and computed tomography
      (CT) contrast agents were investigated. Full thickness cartilage disks (O = 4.0
      mm, n = 64) were prepared from fresh bovine patellae. Contrast agent
      (gadopentetate: Magnevist((R)), gadodiamide: Omniscan, ioxaglate: Hexabrix or
      sodium iodide: NaI) diffusion was allowed either through the articular surface or
      through the deep cartilage. CT imaging of the samples was conducted before
      contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three
      samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral
      quantitative computed tomography (pQCT) instrument. With all contrast agents, the
      diffusion through the deep cartilage was slower when compared to the diffusion
      through the articular surface. With ioxaglate, gadopentetate and gadodiamide it
      took over 29 h for diffusion to reach the near-equilibrium state. The slow
      diffusion of the contrast agents raise concerns regarding the validity of
      techniques for FCD estimation, as these contrast agents may not reach the
      equilibrium state that is assumed. However, since cartilage composition, i.e.
      deep versus superficial, had a significant effect on diffusion, imaging of the
      nonequilibrium diffusion process might enable more accurate assessment of
      cartilage integrity.

PMID- 19864700
TI  - Optical-thermal characterization of cutaneous transilluminators.
AB  - In recent years, there has been an increase in the popularity of light-emitting
      diode (LED)-based, battery-powered transilluminators (BPTs) for facilitating
      transdermal vascular access in adults and neonates. BPTs are believed to have
      lower potential for inducing skin burns than prior devices based on high-power
      broadband lamps; however, the optical and thermal outputs of BPTs are not well
      documented and safety limits for these devices are not well established. In this
      study, we characterize and assess the optical and thermal outputs of six BPTs
      that incorporate red, orange and white LEDs. Optical measurements included
      spectral irradiance and peak local irradiance. Thermal measurements included
      transient temperature readings for an exposure time of 4 min in ambient air and
      ex vivo tissue pre-heated to physiological temperatures. The greatest mean
      temperature rise produced in tissue by a non-white-light diode BPT was 2.5
      degrees C, whereas a mean temperature rise of 9.1 degrees C was measured in a BPT
      that incorporated white-light diodes with relatively high irradiance levels. The
      dominant cause of temperature rise was most likely heat generation within the
      devices. Thermal damage analyses based on temperature limits and the Arrhenius
      equation indicate that although some of the devices studied approach the
      threshold for damage, none appear to exceed it under normal operating conditions.
      The results demonstrated that ambient air measurements may be suitable for
      identifying worst-case BPT temperatures. This study highlights the potential risk
      of LED-based medical devices as well as the need for additional research on
      related issues such as neonatal thermal injury thresholds.

PMID- 19864701
TI  - Computerized detection of diffuse lung disease in MDCT: the usefulness of
      statistical texture features.
AB  - Accurate detection of diffuse lung disease is an important step for computerized
      diagnosis and quantification of this disease. It is also a difficult clinical
      task for radiologists. We developed a computerized scheme to assist radiologists
      in the detection of diffuse lung disease in multi-detector computed tomography
      (CT). Two radiologists selected 31 normal and 37 abnormal CT scans with ground
      glass opacity, reticular, honeycombing and nodular disease patterns based on
      clinical reports. The abnormal cases in our database must contain at least an
      abnormal area with a severity of moderate or severe level that was subjectively
      rated by the radiologists. Because statistical texture features may lack the
      power to distinguish a nodular pattern from a normal pattern, the abnormal cases
      that contain only a nodular pattern were excluded. The areas that included
      specific abnormal patterns in the selected CT images were then delineated as
      reference standards by an expert chest radiologist. The lungs were first
      segmented in each slice by use of a thresholding technique, and then divided into
      contiguous volumes of interest (VOIs) with a 64 x 64 x 64 matrix size. For each
      VOI, we determined and employed statistical texture features, such as run-length
      and co-occurrence matrix features, to distinguish abnormal from normal lung
      parenchyma. In particular, we developed new run-length texture features with
      clear physical meanings to considerably improve the accuracy of our detection
      scheme. A quadratic classifier was employed for distinguishing between normal and
      abnormal VOIs by the use of a leave-one-case-out validation scheme. A rule-based
      criterion was employed to further determine whether a case was normal or
      abnormal. We investigated the impact of new and conventional texture features,
      VOI size and the dimensionality for regions of interest on detecting diffuse lung
      disease. When we employed new texture features for 3D VOIs of 64 x 64 x 64
      voxels, our system achieved the highest performance level: a sensitivity of 86%
      and a specificity of 90% for the detection of abnormal VOIs, and a sensitivity of
      89% and a specificity of 90% for the detection of abnormal cases. Our
      computerized scheme would be useful for assisting radiologists in the diagnosis
      of diffuse lung disease.

PMID- 19864702
TI  - Quantification of the optical surface reflection and surface roughness of
      articular cartilage using optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a promising new technique for
      characterizing the structural changes of articular cartilage in osteoarthritis
      (OA). The calculation of quantitative parameters from the OCT signal is an
      important step to develop OCT as an effective diagnostic technique. In this
      study, two novel parameters for the quantification of optical surface reflection
      and surface roughness from OCT measurements are introduced: optical surface
      reflection coefficient (ORC), describing the amount of a ratio of the optical
      reflection from cartilage surface with respect to that from a reference material,
      and OCT roughness index (ORI) indicating the smoothness of the cartilage surface.
      The sensitivity of ORC and ORI to detect changes in bovine articular cartilage
      samples after enzymatic degradations of collagen and proteoglycans using
      collagenase and trypsin enzymes, respectively, was tested in vitro. A significant
      decrease (p < 0.001) in ORC as well as a significant increase (p < 0.001) in ORI
      was observed after collagenase digestion. After trypsin digestion, no significant
      changes in ORC or ORI were observed. To conclude, the new parameters introduced
      were demonstrated to be feasible and sensitive to detect typical OA-like
      degenerative changes in the collagen network. From the clinical point of view,
      the quantification of OCT measurements is of great interest since OCT probes have
      been already miniaturized and applied in patient studies during arthroscopy or
      open knee surgery in vivo. Further studies are still necessary to demonstrate the
      clinical capability of the introduced parameters for naturally occurring early OA
      changes in the cartilage.

PMID- 19864703
TI  - Using surface imaging and visual coaching to improve the reproducibility and
      stability of deep-inspiration breath hold for left-breast-cancer radiotherapy.
AB  - Late cardiac complications may arise after left-breast radiation therapy. Deep
      inspiration breath hold (DIBH) allows reduction of the irradiated heart volume at
      the same time as it reduces tumor bed motion and increases lung sparing. In the
      present study, we have evaluated the improvement in reproducibility and stability
      of the DIBH for left-breast-cancer treatment when visual coaching is provided
      with the aid of 3D video surface imaging and video goggles. Five left-breast
      cancer patients and fifteen healthy volunteers were asked to perform a series of
      DIBHs without and with visual coaching. Reproducibility and stability of DIBH
      were measured for each individual with and without visual coaching. The average
      reproducibility and stability changed from 2.1 mm and 1.5 mm, respectively,
      without visual feedback to 0.5 mm and 0.7 mm with visual feedback, showing a
      significant statistical difference (p < 0.001 for reproducibility, p < 0.01 for
      stability). Significant changes (>2 mm) in reproducibility and stability were
      observed in 35% and 15% of the subjects, respectively. The average chest wall
      excursion of the DIBH with respect to the free breathing preceding the DIBH was
      found to be 11.3 mm. The reproducibility and stability of the DIBH improve
      significantly from the visual coaching provided to the patient, especially in
      those patients with poor reproducibility and stability.

PMID- 19864704
TI  - Measurement and calculation of characteristic prompt gamma ray spectra emitted
      during proton irradiation.
AB  - In this paper, we present results of initial measurements and calculations of
      prompt gamma ray spectra (produced by proton-nucleus interactions) emitted from
      tissue equivalent phantoms during irradiations with proton beams. Measurements of
      prompt gamma ray spectra were made using a high-purity germanium detector
      shielded either with lead (passive shielding), or a Compton suppression system
      (active shielding). Calculations of the spectra were performed using a model of
      both the passive and active shielding experimental setups developed using the
      Geant4 Monte Carlo toolkit. From the measured spectra it was shown that it is
      possible to distinguish the characteristic emission lines from the major
      elemental constituent atoms (C, O, Ca) in the irradiated phantoms during delivery
      of proton doses similar to those delivered during patient treatment. Also, the
      Monte Carlo spectra were found to be in very good agreement with the measured
      spectra providing an initial validation of our model for use in further studies
      of prompt gamma ray emission during proton therapy.

PMID- 19864705
TI  - REM sleep estimation only using respiratory dynamics.
AB  - Polysomnography (PSG) is currently considered the gold standard for assessing
      sleep quality. However, the numerous sensors that must be attached to the subject
      can disturb sleep and limit monitoring to within hospitals and sleep clinics. If
      data could be obtained without such constraints, sleep monitoring would be more
      convenient and could be extended to ordinary homes. During rapid-eye-movement
      (REM) sleep, respiration rate and variability are known to be greater than in
      other sleep stages. Hence, we calculated the average rate and variability of
      respiration in an epoch (30 s) by applying appropriate smoothing algorithms.
      Increased and irregular respiratory patterns during REM sleep were extracted
      using adaptive and linear thresholds. When both parameters simultaneously showed
      higher values than the thresholds, the epochs were assumed to belong to REM
      sleep. Thermocouples and piezoelectric-type belts were used to acquire
      respiratory signals. Thirteen healthy adults and nine obstructive sleep apnea
      (OSA) patients participated in this study. Kappa statistics showed a substantial
      agreement (kappa > 0.60) between the standard and respiration-based methods. One
      way ANOVA analysis showed no significant difference between the techniques for
      total REM sleep. This approach can also be applied to the non-intrusive
      measurement of respiration signals, making it possible to automatically detect
      REM sleep without disturbing the subject.

PMID- 19864706
TI  - Estimating intratidal nonlinearity of respiratory system mechanics: a model study
      using the enhanced gliding-SLICE method.
AB  - In the clinical situation and in most research work, the analysis of respiratory
      system mechanics is limited to the estimation of single-value compliances during
      static or quasi-static conditions. In contrast, our SLICE method analyses
      intratidal nonlinearity under the dynamic conditions of mechanical ventilation by
      calculating compliance and resistance for six conjoined volume portions (slices)
      of the pressure-volume loop by multiple linear regression analysis. With the
      gliding-SLICE method we present a new approach to determine continuous intratidal
      nonlinear compliance. The performance of the gliding-SLICE method was tested both
      in computer simulations and in a physical model of the lung, both simulating
      different intratidal compliance profiles. Compared to the original SLICE method,
      the gliding-SLICE method resulted in smaller errors when calculating the
      compliance or pressure course (all p < 0.001) and in a significant reduction of
      the discontinuity error for compliance determination which was reduced from 12.7
      +/- 7.2 cmH(2)O s L(-1) to 0.8 +/- 0.3 cmH(2)O s L(-1) (mathematical model) and
      from 7.2 +/- 3.9 cmH(2)O s L(-1) to 0.4 +/- 0.2 cmH(2)O s L(-1) (physical model)
      (all p < 0.001). We conclude that the new gliding-SLICE method allows detailed
      assessment of intratidal nonlinear respiratory system mechanics without
      discontinuity error.

PMID- 19864707
TI  - Interchangeability between heart rate and photoplethysmography variabilities
      during sympathetic stimulations.
AB  - Photoplethysmography variability (PPGV) is currently considered to be a good
      surrogate to heart rate variability (HRV) measurements using the time between two
      pulse waves instead of RR intervals. Nevertheless, the interchangeability between
      HRV and PPGV has never been evaluated in situations with severe alterations in
      the autonomic nervous system (ANS). We aimed to identify the conditions for a
      correct utilization of PPGV in evaluating the consequences of sympathetic
      stimulations. Nine subjects performed three tests: active orthostatic test, slow
      walk and moderate and exhaustive cycling exercises in the supine position. Pulse
      waves at the fingertip and RR intervals were recorded at the same time. We used
      correlations and the Bland and Altman method to compare and evaluate
      interchangeability between several HRV indices. Bland and Altman analysis
      highlighted small discrepancies between PPGV and HRV for all HRV indices in the
      supine position and for LF(ms)(2), HF(ms)(2), LF(peak) and RMSSD in the upright
      position. During the slow walk, it was impossible to detect properly PPG peaks.
      We observed large differences between the two methods during the cycling
      exercise. In conclusion, PPGV can be used instead of HRV without reserve in the
      supine position but only for some HRV indices in the upright position and not
      during slow walk and cycling exercise.

PMID- 19864708
TI  - Physiology of the sphincter of Oddi--the present and the future?--Part 1.
AB  - The mechanisms controlling the sphincter of Oddi (SO) have received considerable
      attention over the past two decades. Progress towards their elucidation has been
      slow, perhaps because of the sphincter's relative inaccessibility and the
      different responses of the human "resistor" as compared to the "pumper" observed
      in several animal models. The list of agents affecting the sphincter grows
      alarmingly. In this review, divided into two parts, substances have been
      classified as neurotransmitters, hormones, local factors and pharmacological
      agents. The first part considers the roles of neurotransmitters. These include
      (a) vasoactive intestinal polypeptide (VIP) and nitric oxide (NO). Both cause
      relaxation. A recent model of their complex interrelationships in smooth muscle
      is described. (b) Substance P (SP) and enkephalins. These produce contractions.
      The former can act directly. An indirect effect via cholinergic neurones may be
      the result of SP release from vagal afferents. (c) Catecholamines, which cause
      contraction or relaxation via activation of alpha- or beta-adrenoreceptors,
      respectively. In the second part attention is focussed on cholecystokinin (CCK)
      which normally relaxes the SO via neuronal mechanisms. A CCK-sensitive pathway
      from sensory duodenal neurones to SO ganglia has been described. Reactive oxygen
      species are among the local factors discussed. Their description as being "the
      good, the bad and the ugly" seems merited. Pharmacological agents include NO
      donors, octreotide and botulinum toxin (BTX). Octreotide induces tachyoddia and
      may impair biliary flow. BTX has exciting potential in the diagnosis of SO
      abnormalities and as a therapeutic alternative to sphincterotomy. In both parts
      of the review current concepts of different aspects of smooth muscle control are
      presented. In several instances data regarding the SO is lacking. We discuss (a)
      the role of interstitial cell of Cajal in the control of slow waves, (b)
      different pathways contributing to tonic and phasic contractions, (c) the 4
      levels of neural control, (d) interrelationships of immune and nervous systems,
      and (e) links between emotional states and gut functions.

PMID- 19864709
TI  - Restorative proctocolectomy--a nine year experience at the King Faisal specialist
      hospital.
AB  - INTRODUCTION: Inflammatory bowel disease and Familial Adenomatous Polyposis (FAP)
      are relatively uncommon in Gulf Arabs. Restorative proctocolectomy with ileal
      pouch-anal anastomosis (IPAA) is a surgical method for treating patients with
      mucosal ulcerative colitis (MUC) and FAP. This paper documents a small experience
      with this operation in Saudi Arabia. METHODS: The charts of all patients who had
      either MUC or FAP and in whom an IPAA had been performed were identified and were
      examined in order to determine patient demographics, timing and staging of
      operation, operative and long term morbidity and mortality and pouch function.
      RESULTS: Thirty patients underwent IPAA. There were 16 males. 29 pouches were J
      pouches. 1 patient was lost to follow up. Surgery was performed for fulminating
      MUC in 9 patients, failed medical treatment in 12, FAP in 7 and megacolon in 2.
      An emergency-three stage IPAA was performed in 10 patients. 3 patients received
      perioperative TPN. 17 were on steroid medication. 12 developed transient
      anastomotic stricture. 8 developed small bowel obstruction during follow up but
      none needed further surgery. 1 patient developed 'pouchitis'. Two pouches were
      removed. The mean daily and nocturnal bowel frequency was 6 and 2 motions per
      day. 6 patients suffered nocturnal leakage. CONCLUSION: The operation of
      restorative proctocolectomy can be performed safely, for the few patients who
      needed the operation in Saudi Arabia.

PMID- 19864710
TI  - Management of gastrointestinal smooth muscle tumors: seven years experience of a
      teaching hospital in Saudi Arabia.
AB  - BACKGROUND: Gastrointestinal (GI) smooth muscle tumors are a group of intramural
      GI tumors formerly known as leiomyoma and leiomyosarcoma. This retrospective
      study was made to review our experience in surgical management of GI smooth
      muscle tumors. METHODS: The clinical records for patients with GI smooth muscle
      tumors during 1993-1999 were reviewed. RESULTS: Ten tumors were located in
      stomach. Abdominal pain was the main presenting symptom followed by GI bleeding.
      The preoperative diagnosis was made by enhanced computerized tomography (CT) on
      eleven patients out of thirteen, while upper GI endoscopy with biopsy identified
      six tumors out of thirteen patients had the test. Tumors were treated by
      conservative excision in four and radical excision in fourteen. Histology was
      leiomyoma in six patients (with mitotic figures < 4 per 10 high power field) and
      leiomyosarcoma was found in twelve patients (with mitotic figures> 4 per 10 high
      power field). Median follow-up was 4 years. There was one recurrence for
      leiomyoma (size: 6 cm). All patients with leiomyosarcoma presented later with
      metastasis and died. CONCLUSION: Size and mitotic activity of tumors are the main
      determinant factors. Enhanced CT remains the proper diagnostic tool.

PMID- 19864711
TI  - Formol-ether concentration method in the diagnosis of active schistosoma mansoni
      in patients with detectable IHA.
AB  - Schistosomiasis is a world wide human infection. In Saudi Arabia there are
      multiple endemic foci. Various methods have been used to diagnose Schistosoma
      mansoni. We studied 1410 patients coming from S. mansoni endemic areas with
      detectable antibodies by indirect hemagglutination (IHA). Stool specimens were
      tested for S. mansoni ova by direct smear and formol-ether concentration (FEC)
      methods. The objective of the study was to identify patients with active
      schistosomiasis using FEC method and a single direct smear. Twenty percent of IHA
      positive patients had active infection detected by FEC, while a single direct
      stool smear diagnosed only 2.4% (P< 0.0001). The percentage of positive FEC was
      significantly increasing in linear trend with IHA level. This trend wasn't
      observed with direct smear examination. The current data suggest that FEC is
      helpful to diagnose active schistosomiasis, therefore it is recommended in IRA
      positive individuals.

PMID- 19864712
TI  - Lichen planus exacerbation by interferon-alpha-2A for chronic viral hepatitis C.

PMID- 19864713
TI  - Ileo-caecal volvulus post-cesarean section: a case report.

PMID- 19864714
TI  - Fatal complication of Henoch-Schonlein purpura: case report and literature
      review.

PMID- 19864715
TI  - Endoscopic management of postcholecystectomy bile duct injuries: review.
AB  - Injuries to the biliary tree arising as a consequence of cholecystectomy,
      continue to be significant complicating factors. The advent of laparoscopic
      cholecystectomy has resulted in a further rise in the incidence of these
      injuries. Various means of investigation are available to assess the site, extent
      and severity of the damage to the biliary tree. Lately, the endoscopic option
      seems to have gained popularity in the management of these patients as it can
      combine both the investigative and therapeutic arms in one common procedure. This
      procedure is recommended as the primary modality of intervention gaining
      precedence over the radiological and surgical options. Since limitations exist in
      managing these patients with endoscopic retrograde cholangiopancreatography, a
      combined approach between the endoscopist, surgeon and radiologist, is the most
      practical option. In this article, we review the various types of biliary
      injuries, their reported incidence, etiological factors, the diagnostic means
      available, and the endoscopic management of each.

PMID- 19864716
TI  - Hepatitis G virus (HGV) infection in Saudi dialysis patients and healthy
      controls.
AB  - BACKGROUND: Viral hepatitis is a global health problem with a high mortality
      rate. End stage renal disease (ESRD) patients have a high prevalence of Hepatitis
      B and C virus infection. Present study was done to identify the prevalence and
      course of a new isolate Hepatitis G virus (HGV) infection in Saudi dialysis
      patients. METHODS: The pattern of viral hepatitis infection (HBV. HCV and HGV)
      was investigated in 109 Saudi patients with ESRD and 100 healthy Saudi blood
      donors. Donated blood was tested for markers of Hepatitis B, C and G viruses.
      Liver functions were measured and blood picture and liver biopsies were also
      performed at regular intervals. RESULTS: Out of the 109 ESRD patients 68 (62.4%)
      were positive for at least one viral marker: 59 (54.1%) were positive for HCV,
      six (5.5%) were positive for HGV and three (2.8%) were positive for HBsAg. Four
      of the six HGV positive patients were also co-infected with HCV. Eight (8%) of
      the blood donors were positive for at least one viral marker. Elevated ALT levels
      (>4 times normal) were recorded in four out of the six HGV-positive patients
      including three co-infected with HCV. CONCLUSIONS: Our results are in agreement
      with similar studies from different countries and also raise the question about
      the causal relationship between HGV and liver disease among dialysis patients.

PMID- 19864717
TI  - Swallowed foreign body: Is interventional management always required?
AB  - A retrospective study of 20 cases diagnosed as "swallowed foreign body" seen over
      a five-year period (July 1993-June 1998) at Asir Central Hospital was performed.
      Six (30%) were children and 14 (70%) adults. In the children, five were boys and
      one was a girl. Objects swallowed included metal nails. coins, hair pins and a
      chain pendant. In the adult group, eight (57%) were males and six (43%) females.
      Objects swallowed included sewing needles, sharp blades, pieces of glass, paper
      clips and gravel. The swallowed foreign body in all the patients passed
      innocuously through the gastrointestinal tract in two to ten (average 4.7) days.
      Our method of treatment consisted of giving high fiber diet, Metamucil or
      lactulose and liquid paraffin. There was no mortality.

PMID- 19864718
TI  - Factors affecting hospital mortality in acute upper gastrointestinal bleeding.
AB  - This retrospective analysis studied the records of 564 consecutive patients
      admitted to Gastrointestinal Bleeding Unit of Riyadh Medical Complex with acute
      upper gastrointestinal bleeding over a 2-year period (May 1996-April 1998). The
      purpose of the study was to analyze the mortality with an aim to identify the
      risk factors affecting mortality in these patients. Majority of patients were men
      (82%) and Saudis (54%). Their mean age was 52.46 + 17.8 years. Esophageal varices
      (45%) were the main causes of bleeding followed by duodenal ulcers (24%). Overall
      mortality in this series was 15.8% (89 patients). Comorbid diseases were
      responsible for death in 68 (76%) patients, whereas, bleeding was considered to
      be directly responsible for death in 21 (24%) patients. On analysis of data from
      this study, old age (>60 years), systolic pressure < 90 mm Hg on admission,
      comorbid disease, variceal bleeding and Child's grade C in patients with chronic
      liver disease were associated with adverse outcome.

PMID- 19864719
TI  - Leiomyoma of the small bowel - a rare cause of massive gastrointestinal bleeding:
      A case report and literature review.

PMID- 19864720
TI  - Atypical giant cells in the FNA of solitary true cyst of the pancreas: A
      potential diagnostic pitfall - report of case and literature review.

PMID- 19864721
TI  - Crohn's Ileiti's presenting with massive gastrointestinal hemorrhage - case
      report and review of literature.

PMID- 19864722
TI  - The Saudi board of internal medicine: the gastroenterology fellowship training
      program.

PMID- 19864723
TI  - The physiology of the biliary tree. Motility of the gallbladder--part 2.

PMID- 19864724
TI  - The brain of the gut.
AB  - One year before the close of the 19th century it was recognized that intestinal
      peristalsis was controlled by nerve plexuses in the wall of the gut independent
      of the central nervous system (CNS). This concept was developed further during
      the first quarter of the 20th century but was almost forgotten during the next 50
      years until it was revived by the early 1970s. It is now recognized that the
      myenteric and submucous plexuses, referred to as the enteric nervous system
      (ENS), contain as many neurons as in the spinal cord. In addition to autonomy
      from the CNS, the ENS employs not only noradrenaline and acetylcholine but also
      serotonin (5-HT), ATP, peptides and nitric oxide as neurotransmitters, and
      controls gut movements, exocrine and endocrine secretions and the
      microcirculation, thus qualifying for being considered the brain of the gut.
      Reflexes involving the ENS may be entirely intrinsic such as that controlling
      peristalsis, between parts of the gut through prevertebral ganglia e.g. the
      enterogastric reflex, or between the gut and the CNS as examplified by the vago
      vagal reflexes. Absent, defective or dysfunctional enteric neurons may result in
      achalasia, infantile hypertrophic pyloric stenosis, paralytic ileus, intestinal
      pseudo-obstruction, Hirschsprung's disease or idiopathic chronic constipation.
      Further, the ENS may be involved in the pathogenesis of secretory diarrhoea and
      inflammatory bowel disease. More research on the gut brain will deepen our
      understanding of the physiology and pathophysiology of the gastrointestinal
      tract.

PMID- 19864725
TI  - The pattern of lower gastrointestinal disease in the eastern region of Saudi
      Arabia: a retrospective analysis of 1590 consecutive patients.
AB  - To determine the pattern of lower gastrointestinal disease in the Eastern region
      of Saudi Arabia we analysed 1907 colorectal biopsies obtained from 1590
      consecutive patients (1256 males & 334 females), evaluated during a 13 year
      period (1983-1996) in a tertiary care teaching hospital. The age range was 6-81
      years with a mean of 37 + 15. During the same period 6874 new patients were seen
      in the Gastroenterology Clinics. Saudi Arabs constituted 970 (61 %) of all
      patients. The remaining 620 (39%) were non-Saudi, mostly of Arab origin from
      neighbouring countries. The most common presenting symptom for referral was
      abdominal pain (1193 patients, 75%) followed by diarrhea (636 patients, 40%). The
      most frequent histologic diagnosis was a normal mucosa followed by non specific
      proctocolitis accounting respectively for 37.9% and 37.4% of all cases. These
      were followed by schistosomiasis, 113 (7.1%), adenocarcinoma, 91 (5.7%) and
      ulcerative colitis, 91 cases with a relative frequency of 5.7% and a calculated
      prevalence of 1.3%. Of significance was the encounter of 14 cases of Crohn's
      disease amounting to 0.9% of all cases with a calculated prevalence of 0.2%. A
      minority of 83 patients (5.2%) were cases of either a benign polyp, diverticular
      disease, tuberculosis, ischaemia, lymphoma, pseudomembranous colitis (PMC),
      eosinophilic gastroenteritis or malacoplakia. These data show that although a
      "normal mucosa" and "nonspecific proctocolitis" were the dominant diagnoses,
      significantly, ulcerative colitis and Crohn's disease exist and should be
      considered in the differential diagnosis of lower GI disease.

PMID- 19864726
TI  - Use of serum immunoglobulins G and A for detection of Helicobacter pylori
      infection in dyspeptic patients by enzyme immunosorbent assay.
AB  - Since the discovery of Helicobacter pylori (H. pylori), several invasive and non
      invasive tests have become available. The aim of this study was to test the
      performance of immunoglobulins IgG and IgA by using an enzyme linked
      immunosorbent assay (ELISA) test (In vitro diagnostika GmbH, Germany) for the
      diagnosis of H. pylori among dyspeptic patients. Blood samples from 152 dyspeptic
      patients and 51 asymptomatic controls were analyzed in a case control study. IgG
      and IgA were positive in 33.5% and 41.1% respectively compared to 13.8% for both
      IgG and IgA in controls (P=0.002). We support the future use of serology as a non
      invasive, and rapid test for the diagnosis of H. pylori infection among dyspeptic
      patients in areas with low prevalence. Endoscopy remains the method of choice for
      elderly dyspeptic patients and for those with possible gastric or duodenal
      pathology.

PMID- 19864727
TI  - Effect of octreotide on the prevention of hyperamylasemia after ERCP in Saudi
      Arabia: a prospective study.
AB  - BACKGROUND AND OBJECTIVES: Acute pancreatitis is a serious complication of ERCP.
      Octreotide as prophylaxis against ERCP-induced hyperamylasemia has produced
      conflicting results. A review article has called for additional controlled
      studies. This work was undertaken to see the effect of octreotide in ERCP-induced
      enzyme changes in a predominantly Saudi population. SUBJECTS & METHODS: The
      setting was a university teaching hospital, Eastern Saudi Arabia. The study was
      prospective, randomized and controlled and the subjects were 50 consecutive adult
      in-patients. Octreotide, 200 tg subcutaneous, was used in the study group (27
      patients). Levels of serum amylase and lipase were estimated three times post
      ERCP; mean values were compared with the control group (23 patients) using
      student t test. RESULTS: A total of 50 patients were studied. Their mean age was
      43 (range 19 to 70); 30 were female, a male:female ratio of 1:1.5. The two groups
      were comparable in terms of age, sex and nationality as well as clinical,
      haematological and biochemical variables. In both groups, the serum levels of
      amylase and lipase 4 hours post-ERCP were significantly higher compared with base
      line levels. However, there were no statistical differences between the mean post
      ERCP values within as well as between the two groups of patient studied. However,
      the pattern of response appeared to be different when amylase was compared with
      lipase. CONCLUSION: Prophylactic octreotide, in the regimen used in this study,
      does not protect against post-ERCP hyperamylasemia and hyperlipasemia. The
      observed apparent difference in the pattern of serum amylase and lipase remains
      to be confirmed.

PMID- 19864728
TI  - Hepatic granulomas in an arab population: a retrospective study from a teaching
      hospital in Riyadh.
AB  - This is a retrospective analysis of the medical records of 116 patients who
      presented to the gastroenterology division, department of medicine at King Khalid
      University Hospital (KKUH) in Riyadh, Kingdom of Saudi Arabia and subsequently
      had a histopathologic diagnosis of hepatic granulomas. Infections contributed to
      56% and were represented mainly by schistosomiasis and to a lesser extent by
      tuberculosis, brucellosis and hydatid disease. Lymphomas (8%) were the major
      representative of noninfectious causes. The etiology of 25% of granulomas
      remained undetermined. Weight loss, fever, anorexia and abdominal pain were the
      most frequent presenting symptoms in 53, 45, 43 and 42% of patients,
      respectively. Ten percent of the patients were asymptomatic. Hepatomegaly and
      splenomegaly were the predominant physical findings in 55% and 43% of patients
      respectively. Hepatic granulomas in this study are mainly caused by infections.
      Schistosomiasis, tuberculosis and brucellosis represented the most common
      etiologic factors.

PMID- 19864729
TI  - Pneumatosis intestinalis beyond the newborn period.

PMID- 19864730
TI  - Hepatic fascioliasis; a cause of pyrexia of unknown origin and persistant
      eosinophilia.

PMID- 19864731
TI  - Massive melena from a dieulafoy's type ulcer of the jejunum: a case report.

PMID- 19864732
TI  - The physiology of the biliary tree. Motility of the gallbladder--part 1.
AB  - An incomplete picture has emerged of the complex means by which gallbladder
      motility is controlled under normal and pathophysiological conditions. In the
      first part of this review an overall account is presented. The mechanisms of
      cholecystokinin release, its stimulation by dietary factors and peptides
      elaborated by both pancreas and small intestine are discussed. The inhibition of
      cholecystokinin release by bile acids and proteases is also described. In the
      second part attention is focussed on other peptides affecting motility. These
      include (a) octreotide, effective for treatment of acromegaly, (b) peptide YY,
      contributing to a "colonic brake', (c) motilin. associated with interdigestive
      contractions, analogues of which possibly correct gallbladder hypomotility, and
      (d) substance P and calcitonin gene-related peptide, which facilitate ganglionic
      transmission after release from extrinsic sensory neurones and alter gallbladder
      responses to vagal stimulation. The sympathetic nervous system and diabetes
      mellitus also influence vagal responses. The former, acting presynaptically, may
      provide a "brake" to prevent vagal overactivity. The latter could cause
      hypomotility via autonomic neuropathy, although hyperglycaemia, itself, may play
      a role. The role of nitric oxide, released from neurones also producing
      vasoactive intestinal peptide is recognized. Both lengthen muscle, the former
      producing responses without requiring plasma membrane receptors. Gallbladder
      motility also changes during pregnancy and stone formation. Progesterone and
      cholesterol can limit G protein actions, thus impairing contractions.
      Inflammation is associated with abnormal motility. The production of reactive
      oxygen metabolites, acting directly or releasing prokinetic prostaglandins, may
      be responsible. It has been proposed that the gastrointestinal tract may be
      normally in a state of controlled inflammation, primed to react to harmful
      challenges.

PMID- 19864733
TI  - Assessment of Courvoisier's law.
AB  - Courvoisier's Law is frequently interpreted as "A palpable gallbladder is a sign
      of malignancy". In fact, it is the most misquoted signs as he was referring to
      common duct obstruction by stones and other problems, without specifying
      malignancy ! In a retrospective study of 86 cases of distended gallbladder
      between 1987 and 1992, we assessed the validity and the accuracy of this law in
      the diagnosis of bilio-pancreatic diseases, by matching the finding of a palpable
      gallbladder by clinical examination (46 cases: 53%), with CT scan (75 cases:
      87%), and by operative surgery (82 cases: 95%). In four cases, a palpable
      gallbladder spontaneously resolved before the surgical act. In 17 cases, repeated
      palpation of the gallbladder by several medical students or residents in one
      session, resulted in disappearance of the mass under the fingers of the last
      examiner. In 13 of these 17, a palpable gallbladder was again present after 3-7
      days of its disappearance. With the new imaging technology, we may apply the
      implications of Courvoisier's Law to any obstruction of the distal common bile
      duct below the cystic duct, the ampulla of Vater, and the head of pancreas. We
      found this obstruction may be caused by malignancy in 87% and inflammation and
      lithiasis in 13%. A tumor or other obstruction above the cystic duct, will not
      cause distention of the gallbladder.

PMID- 19864734
TI  - The beneficial effect of alpha-tocopherol on liver regeneration after partial
      hepatectomy on rats.
AB  - Liver, a unique organ, is the only organ which has the ability to regenerate
      after partial hepatectomy. It can return to normal mass several weeks after 70%
      partial hepatectomy. The exact mechanism responsible for regeneration is yet to
      be known. This needs further investigation. The aim of this study is to examine
      the role of oxygen free radicals (OFRs) such as superoxide (O(-)2), hydroxyl
      radicals (H2O2 or OH(-)) in liver regeneration after partial hepatectomy (< 70%).
      To evaluate the effect of antioxidant on liver regeneration, rats were pre
      treated intramuscularly with alpha-tocopherol (vitamin E) daily for 3 weeks, and
      continued for 3 weeks post partial hepatectomy (< 70%) liver weight, rat body
      weight were determined in both control (untreated) and treated groups. The
      present results showed significant increase in liver weight in vitamin E treated
      group compared to control. The results of this paper might be useful in throwing
      some light on the role of oxygen free radical scavengers and antioxidants upon
      liver regeneration. This would have a therapeutic utilization in patients with
      liver problems.

PMID- 19864735
TI  - Laparoscopic cholecystectomy: rate and predictors for conversion.
AB  - Laparoscopic cholecystectomy (LC) was attempted in 847 patients, 823 (97.2%) were
      completed laparoscopically and 24 (2.8%) had to be converted to open
      cholecystectomy (OC). Acute cholecystitis was the commonest reason for conversion
      (13 out of 24 patients). Patients who had acute cholecystitis are five times at
      risk for conversion to open than other patients with non-acute cholecystitis (p<
      0.001). Age and sex were not statistically significant predictors for conversion.
      There were no mortalities and no major bile duct injuries in our series. These
      data confirms the safety of LC, identify factors which predicts conversion to OC
      and may be helpful in selecting patients for day care ambulatory LC.

PMID- 19864736
TI  - Pediatric colonoscopy: King Khalid University Hospital experience.
AB  - Pediatric colonoscopy is now an established procedure to evaluate colonic
      disease. As there is no reports about pediatric colonoscopy in our community a
      retrospective study was carried in KKUH to analyze the pediatric colonoscopies.
      This is a retrospective study over 15 years period in KKUH to analyze the
      pediatric colonoscopy. Sixty-six colonoscopies were done in sixty-two patients.
      The age ranged from 6 month to 16 years; with 35 males and 27 females. Forty
      seven of the patients were Saudi. Indication for colonoscopy were bleeding per
      rectum thirty-two, diarrhea ten, abdominal pain seven, ulcerative colitis in
      four, suspected polyps in five and other indication in seven patients. In 33
      patients colonoscopy was done without premedication, 11 patient had sedation
      while 22 had general anesthesia. Colonoscopy revealed abnormal finding in 64%,
      normal findings 28.7% and due to poor preparation no endoscopic report in 7.3%.
      The commonest abnormal finding were ulcerative colitis in 19 patients and polyps
      in 17 patients. Pediatric colonoscopy is a safe, practical rewarding procedure
      especially in certain categories of patients mainly those suspected to have
      ulcerative colitis, rectal bleeding or diarrhea. A high index of suspicion of
      ulcerative colitis will lead to better management of patients.

PMID- 19864737
TI  - The changing sensitivity of Helicobacter pylori to metronidazole.
AB  - The objective was to determine over two periods, seven years apart, the
      sensitivity of H. pylori isolates to metronidazole, tetracycline and
      erythromycin. The study periods were 1987/88 and 1995/96 and the population
      consisted of 133 patients undergoing upper gastrointestinal endoscopy for peptic
      ulcer disease in KFHU. The sensitivity of H. pylori isolates from their biopsy
      specimens was tested to three antibiotics using the disc diffusion method. In
      1987/88, 62%, 97.0% and 98.6% of isolates were sensitive to metronidazole,
      erythromycin and tetracycline respectively. The corresponding sensitivities in
      1995/96 were 14.5, 93.5% and 100% respectively. In 1987/88 there was no
      difference in the metronidazole resistant H. pylori isolates from men and women
      (38.2% vs 37.5%) but in 1995/96 slightly more women than men had metronidazole
      resistant isolates (89% vs 82.9%). The resistance of H. pylori to metronidazole
      increased over time. In order to improve outcome of treatment, sensitivity of H.
      pylori isolates needs to be determined for each patient. The recommended triple
      therapy requires to be modified if the prevailing sensitivity pattern of H pylori
      in our environment is taken into account.

PMID- 19864738
TI  - The association between Helicobacter pylori infection and lymphoid reaction in
      patients suffering from dyspepsia in Bahrain.
AB  - Lymphoid reaction to Helicobacter pylori (H. pylori ) infection varies from
      simple aggregates to primary gastric lymphoma. This study analyzes various
      lymphoid reaction to H. pylori infection among 102 patients with dyspepsia in
      Bahrain during 1994-1995. Cases underwent gastroscopy for gastrointestinal
      complaints and at least four biopsies were taken from each patient. The
      prevalence of H. pylori among the study group was 79.4%. Males constituted 63.7%.
      Lymphoid reaction in the form of lymphoid follicles and lymphoid aggregates were
      found in 31.4% and 24.5% respectively. The Odds Ratio (OR) of developing lymphoid
      reaction among H. pylori infected cases, compared to non- H. pylori subjects was
      20.1:1, and the relative risk (RR) was 7.13. The OR of developing lymphoid
      follicles among H. pylori cases compared to non-H. pylori subjects was 11:1 and
      the RR was 5.63.

PMID- 19864739
TI  - Small intestinal obstruction in pregnancy and puerperium.
AB  - The problem of intestinal obstruction in pregnancy and puerperium is worsened by
      the risk it poses not just to the mother, but also to the fetus. In this review
      of 10 pregnant/puerperium patients the maternal mortality was 10% and fetal
      wastage 20%. In pregnancy and puerperium, intestinal obstruction carries a higher
      mortality, 10-33%, than in non-pregnant patients, 6-10%. The rarity of the
      problem, delay in diagnosis, anxiety over radiological examination in pregnant
      women, worry over laparotomy in pregnant women, all result in delay in
      instituting definite treatment and contribute to the morbidity. Application of
      established principles in the management of intestinal obstruction even when it
      occurs in pregnancy and puerperium might help to improve the results of
      management and reduce the current level of morbidity and mortality.

PMID- 19864740
TI  - Combined percutaneous and endoscopic approach for internal biliary drainage: the
      rendezvous maneuver--a report of four cases.

PMID- 19864741
TI  - Submucosal lipoma causing an unusual presentation of intussusception.

PMID- 19864742
TI  - Writing a clinical research paper.
AB  - A well-known unwritten law in institutions of higher learning is that of "Publish
      or perish". The duties of a University teacher, in order of priority are
      teaching, research and service. Reasons for writing clinical research papers are
      to get promoted, to get research grants and to make known, one's findings in
      order to improve patients' care. Writing papers is also a means of delivering
      continuous education, therefore publication is essential for any one pursuing an
      academic career. Research papers can be in the form of case reports,
      retrospective studies, prospective studies and laboratory or animal research. Two
      popular formats of writing papers are: The Vancouver Style and the Harvard
      System.

PMID- 19864743
TI  - Hepatitis G virus (HGV) and liver diseases.
AB  - Recently, a new flavi-like virus, provisionally named hepatitis GBV-C or
      hepatitis G virus (HGV), has been described and was initially thought to be the
      major etiological agent of non-A-E hepatitis. HGV does not induce an immune
      response that is consistently detectable by using recombinant proteins from
      prokaryotic expression and hence prevalence studies have been conducted by using
      polymerase chain reaction (PCR)-based system. HGV-RNA has been detected in many
      human populations. This article reviews what has been investigated about HGV from
      normal blood donors, patients with liver disease, patients at risk of acquiring
      the infection to possible perinatal and sexual transmission of the virus. Based
      on the conclusions that can be drawn from these studies conducted so far, the
      association between HGV infection and liver disease is still not certain. It is
      possible that HGV might play a role in other diseases not involving the liver,
      but at the present time HGV can be considered as an orphan flavivirus still
      looking for a human disease.

PMID- 19864744
TI  - Laparoscopic cholecystectomy is feasible and safe in acute cholecystitis.
AB  - OBJECTIVE: To assess the feasibility and safety of laparoscopic cholecystectomy
      in acute cholecystitis. SUBJECTS AND METHODS: Between June 1993 and December
      1996, 424 consecutive patients underwent laparoscopic cholecystectomy; 45 (10.6%)
      had acute cholecystitis confirmed by ultrasound. RESULTS: All 45 patients were
      opened within 72 hours of admission. Conversion to open cholecystectomy was
      necessary in three patients (6.7%). The mean operating time was 126 minutes
      (range: 40-300 minutes). There was no mortality or common bile duct injury in
      this series. The postoperative stay averaged 3.9 days (range: I to 11 days).
      There was no delayed morbidity after a mean follow-up of 2 years. CONCLUSION:
      Laparoscopic cholecystectomy is feasible and safe in patients with acute
      cholecystitis, provided it is performed by experienced surgeons. Although the
      procedure is somewhat lengthy, it is associated with low conversion rate, no
      serious morbidity and zero mortality.

PMID- 19864745
TI  - Esophageal candidiasis among a dyspeptic population.
AB  - This is a retrospective study of 59 patients endoscoped over a period of six
      years at a private clinic and were found to have esophageal candidiasis. The
      median age was 46.38 years. Thirty (51 %) patients had no precipitating factors.
      Only 18 (30%) patients had typical symptoms. The distal part of the esophagus was
      more often involved. The thrush was scattered in 57 (97%) patients. The
      endoscopic finding was confirmed by cytology in all patients included. Symptoms
      improved on oral nystatin treatment and simultaneous treatment of associated
      conditions in all 46 patients followed up. In conclusion, esophageal candidiasis
      appear to be not uncommon among dyspeptic population. It presents more frequently
      with atypical symptoms and responds well to oral nystatin treatment.

PMID- 19864746
TI  - Frequency of endoscopic esophagitis in nutcracker patients with pathological 24
      hour pH monitoring.
AB  - Endoscopically, it was claimed that reflux esophagitis is less frequently seen in
      patients with tertiary contractions. The aim of this prospective study is to
      evaluate the frequency of endoscopic esophagitis in nutcracker patients with
      pathological 24-hour pH monitoring as compared to a matched group of patients
      with pathological prolonged ambulatory pH monitoring. The study included eight
      patients with nutcracker esophagus and pathological 24-hour pH monitoring (Group
      1); mean (SD) age was 36.5 (10.6) years, mean (SD) LES pressure was 11 (2.9) mmhg
      and % total pH < 4 was 11.5 (7), which were not statistically different from a
      matched control of 25 patients (Group 2). Patients with underlying definable
      systemic diseases were excluded from the study.. Three nutcracker esophagus and
      eight control showed evidence of endoscopic esophagitis (P value=0.9). Among
      group I, nutcracker patients with endoscopic esophagitis had a tendency towards a
      lower LES pressure (P=0.056) and a significantly greater % total pH < 4 (P=0.04).
      % upright reflux (P=0.03) and total time pH < 4 (P=0.003) than nutcracker without
      endoscopic oesophagitis. Moreover, nutcracker patients with endoscopic
      esophagitis had a significantly greater % total pH < 4 and total time pH < 4 than
      control group with endoscopic esophagitis with P value = 0.03 and 0.02,
      respectively. CONCLUSION: The frequency of endoscopic esophagitis is similar in
      nutcracker and a matched control with pathological 24-hour pH monitoring.

PMID- 19864747
TI  - Radionuclide esophageal transit time for the assessment of pneumatic dilation in
      patients with achalasia.
AB  - OBJECTIVE: The aim of this study was to assess the value of radionuclide
      esophageal transit time (RET) in prediction of the results of pneumatic dilation
      in patients with achalasia. PATIENTS AND METHODS: Thirty patients (13 males) with
      a mean age of 37 +/- 15.6 years (range 17-73 years) were included in the study.
      All patients were diagnosed to have idiopathic achalasia of the cardia and
      selected for pneumatic dilation. Each patient had three RET, two the same day of
      dilation (pre-and postdilation) and a third follow up one within three months of
      dilation (4 patients failed to come for follow up and were excluded). RESULTS:
      Several parameters were derived from RET studies, T/50: time required for 50% of
      activity in the esophagus to be cleared, T/10 : time required for 90% of activity
      in the esophagus to be cleared and percentage clearance at 10 min. These
      parameters were compared to response of dysphagia to dilation. It was evident
      that the higher the esophageal clearance postdilation, the better the outcome.
      When immediate post dilation clearance was 85% or more the success rate was 83.3%
      whereas when it was 20-50% the success rate was only 21.4%. No relation was found
      between T/50, T/10 and dysphagia response. CONCLUSION: RET appears to be a useful
      quantitative procedure in the assessment of pneumatic dilation outcome in
      achalasia patients.

PMID- 19864748
TI  - Pattern of gastrointestinal diseases in adult patients admitted to Samtah General
      Hospital, Gizan region, Saudi Arabia.
AB  - To determine the relative frequencies of gastrointestinal diseases (GI) in
      patients admitted to Samtah General Hospital, Gizan, the records of 2,442 adults
      admitted to the medical and surgical services for gastrointestinal diseases
      during the period 1413 to 1416 were analyzed retrospectively. 1,028 patients had
      acute appendicitis. The remaining 1,414 patients were admitted for various other
      GI diseases. In these 1,414 patients the commonest diseases were gastrointestinal
      infections (36.4%), peptic ulcer disease (19%), gall bladder disease (18.5%),
      viral hepatitis and its sequelae (20.7%). Despite the high prevalence of
      cholelithiasis, acute pancreatitis was uncommon (0.1 %). Inflammatory bowel
      disease was rare. There was no gender - related difference in the prevalence of
      gastrointestinal infections, peptic ulcer disease and carcinoma of the stomach.
      Males were significantly more afflicted than females with viral hepatitis (p<
      0.0001), cirrhosis of the liver (p< 0.0001), hepatocellular carcinoma (p<
      0.0005), variceal bleeding (p< 0.0005), and peptic ulcer bleeding (p< 0.005). As
      a large proportion of our patients had preventable diseases, it is expected that
      immunization and other public health measures will reduce the frequency of these
      diseases in the future.

PMID- 19864749
TI  - Comparison of H. pylori-gastritis among young and old patients by using "the
      modified Sydney system of classification and grading".
AB  - It is well known that the age at which H. pylori infection is acquired is crucial
      in the genesis of gastric cancer. The aim of the study is to compare antral
      biopsies from younger (age range 3 - 20 years) and older (age range 51 - 60
      years) patients infected with H. pylori. The biopsies were graded for five
      parameters according to the guidelines from "The modified Sydney System of
      Classification and Grading of gastritis". There was no significant difference in
      three parameters i.e. H. pylori density, neutrophilic activity and chronic
      inflammation between the two age groups. Two parameters i.e. the mucosal atrophy
      and intestinal metaplasia were, however, more prevalent in older age group. They
      are considered preneoplastic for gastric cancer. This study demonstrated that the
      intensity of inflammation is not age related. Preneoplastic changes do, however,
      begin to emerge later in life.

PMID- 19864750
TI  - Childhood obesity: referred cases to a tertiary health center in Riyadh, Saudi
      Arabia.
AB  - OBJECTIVE: To show the pattern of etiology of childhood obesity referred to our
      endocrinology clinic between December 1989 and December 1994. SUBJECT AND
      METHODS: All the children referred to our clinic at the above stipulated dates
      were studied. This is a retrospective medical records review of these patients.
      The patients' height and weight were measured by trained staff of the clinic. The
      Quetelet index also known as Body Mass Index (BMI) was calculated as weight
      (kg)/height (m)2 for each patient. Laboratory data as well as results of clinical
      investigations were also obtained from the records of the patients. RESULTS: 52
      patients with ages ranging between 2 years and 16 years (median 8 years) were
      studied. Male:female ratio was 1:1.35 (67.3%) of the patients were Saudis while
      17 (32.7%) were non-Saudis. The etiology of obesity among the series were
      nutritional 46 (88.5%), Prader-Willi Syndrome 3 (5.8%), Laurence-Moon-Biedl
      Syndrome 1 (1.9%), pseudohypoparathyroidism 1 (1.9%) and hypothyroidism 1 (1.9%).
      The study showed that the majority of the patients had simple nutritional
      obesity.

PMID- 19864751
TI  - Primary peritonitis revisited.

PMID- 19864752
TI  - Alpha 1-antitrypsin deficiency and related liver disease.
AB  - Alpha1-antitrypsin (alpha1 AT) deficiency is a relatively common genetic cause of
      liver disease among Caucasians. It is an autosomal recessive disorder
      characterized by reduced serum levels of alpha1 AT, a 52-kD glycoprotein that
      functions as an antiprotease. The deficiency state is caused by mutations in the
      alpha1 AT gene on chromosome 14. Alpha1 AT shows considerable genetic
      variability, having more than 75 genetic variants (Pi types). The PiZ allele is
      the most common deficiency variant. PiZZ homozygotes have 15-20% of the normal
      plasma levels of alpha1 AT. The deficiency is due to lack of secretion of Z
      alpha1 AT from the hepatocyte, where inclusions are formed in the endoplasmic
      reticulum. Homozygous alpha1 AT deficiency (PiZZ) is known to predispose to
      emphysema and chronic liver disease. This review outlines the clinical
      manifestations and treatment of alpha1 AT deficiency associated liver disease,
      focusing on recent advances in the pathogenic mechanism of liver disease in this
      genetic disorder.

PMID- 19864753
TI  - Endoscopic features of Helicobacter pylori induced gastritis.
AB  - It's still controversial whether certain macroscopic endoscopic features can be
      used to diagnose Helicobacter pylori (HP) related gastritis. The literature
      dealing with this subject is confusing, because of the lack of precise
      terminology, no large control trials, major discrepancies in interpretations of
      macroscopic changes and poor correlation of the macroscopic appearance and
      histological finding of gastritis. We conducted a prospective study of 208
      dyspeptic patients, who underwent upper gastrointestinal endoscopies from
      February 1997 to June 1997. Only those patients who had either normal looking
      gastric mucosa or macroscopic gastritis were included in the study.
      Endoscopically normal looking mucosa was seen in 67 patients (65.6%),
      erythematous gastritis in 51 (74%), mosaic appearance in 18 (88%), erosive
      gastritis in 14 (85%), nodular gastritis in 17 (94%), atrophic gastritis in 12
      (75%), and fundal rugae hypertrophies in 5 (80%). We suggest that the antral
      nodularity, raised erosions, mosaic appearance and mixed findings, are the
      reliable indicators of the underlying HP induced gastritis. However, these
      endoscopic findings are very specific, though not sensitive, for HP gastritis.

PMID- 19864754
TI  - Association of gastric lymphoid follicles and Helicobacter pylori infection.
AB  - Lymphoid tissue is normally absent in the gastric mucosa; however, lymphoid
      follicles are very frequently noted in Helicobacter-associated gastritis. We
      reviewed 237 cases of chronic gastritis with lymphoid follicles. Out of this 227
      cases (95.8%) were found to have H. pylori infection. The significance of this
      finding and its possible relationship to primary gastric lymphoma are discussed.

PMID- 19864755
TI  - The psychopathology of duodenal ulcer compared with functional dyspepsia: a case
      control study.
AB  - This is a prospective study of the psychiatric morbidity in 80 patients with
      duodenal ulcer, 80 with functional dyspepsia and 80 healthy controls; matched for
      age, sex and marital status. A semi structured psychiatric interview and clinical
      mental state examination were used in the psychiatric assessment of the patients
      and controls. Psychiatric diagnoses were made according to DSM3-R. A modified
      version of Life Events Scale by Tennant and Andrews was used in the assessment of
      life events in relation to psychiatric illness. Psychiatric illness was
      significantly more in the patients than the controls. Anxiety and depressive
      disorders dominated the clinical picture and the symptoms were usually of mild
      nature. Other neurotic were rare and psychotic illness was absent. Though more
      psychiatric patients experienced life events than the controls, differences,
      however were not statistically significant. Further studies are needed,
      especially in relation to the causative association between the functional
      dyspepsia and psychiatric disturbances.

PMID- 19864756
TI  - Radiological evaluation of patients after laparoscopic cholecystectomy.
AB  - The objective of this study is to describe the normal, abdominal radiological
      findings after laparoscopic cholecystectomy that could be confused with a
      pathological process. Thirty-one patients, who had laparoscopic cholecystectomy
      were prospectively studied. They underwent supine and erect abdominal X-rays, on
      the first and second postoperative days. In 19 patients (61 %) no residual free
      intraperitoneal gas was seen. In 12 patients (39%) small amounts of free gas were
      noticed 24 hours postoperatively, and in six (19%), some free intraperitoneal gas
      was seen after 48 hours. Distention of the colon was noticed in 17 (55%), and was
      mainly in the hepatic flexure area in nine of these patients (29%). Eight
      patients complained of shoulder pain. This study shows that pneumoperitoneum
      tends to disappear within 48 hours of laparoscopic cholecystectomy. When present,
      there is usually no cause for alarm as long as patients show no evidence of
      clinical disturbance.

PMID- 19864757
TI  - TC-99m-labeled red blood cell scintigraphy in the investigation of patients with
      hepatic cavernous hemangioma.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of 99mTc-red blood cell
      scintigraphy in the diagnosis of hepatic cavernous hemangiomas. PATIENTS AND
      METHODS: Sixty three patients, 56 females (89%) and 7 males (1 I%), with ages
      between 22 and 54 years (median 33 years) were investigated for liver masses
      found on ultrasonography of the abdomen. All the patients had undergone 99mTc
      liver-spleen scan followed by 99mTc-red blood cells scintigraphy. The size of the
      lesions ranged between 3 and 9 cm. The final diagnosis was reached through
      cytology, and/or histopathology or follow up for more than 3 years. RESULTS: A
      total of 70 lesions were found as a single lesion in 60 patients and multiple
      (i.e. total of 10 lesions) in the other 3 patients. The results of 99mTc-red
      blood cells scintigraphy, compared to the results of the final diagnosis, showed
      sensitivity and specificity rates of 100% and 89% respectively, positive and
      negative predictive values of 98% and 100% respectively, and accuracy rate of
      98.6%. A single false positive case was a hepatocellular carcinoma. CONCLUSION:
      99mTc- red blood cell scintigraphy is highly accurate in the diagnosis of liver
      cavernous hemangioma and should characterize liver mass found on ultrasonography
      and suspected for hemangioma.

PMID- 19864758
TI  - Gallstone pancreatitis in pregnancy.

PMID- 19864759
TI  - Collagenous colitis: a case report with study of the neuroendocrine markers.

PMID- 19864760
TI  - Spherocytosis presenting with choledocholithiasis in early childhood: a case
      report and review of the literature.

PMID- 19864761
TI  - The pathogenic role of Helicobacter pylori in peptic ulcer disease and non-ulcer
      dyspepsia.

PMID- 19864762
TI  - The irritable bowel syndrome.

PMID- 19864763
TI  - Octreotide: a clinical update.
AB  - Somatostatin is found in the pancreas and gastrointestinal tract, including the
      visceral autonomic nervous system, the endocrine D cells and the gut lumen.
      Somatostatin peptides may act differently at different sites as hormones, as
      paracrine substances or neurotransmitters. So far not much is known on the
      physiological effects of somatostatin in the gastrointestinal tract. Somatostatin
      and octreotide, a synthetic analogue with a longer half-life and higher potency,
      inhibit the neuroendocrine and exocrine gastrointestinal secretion, intestinal
      glucose, fat and amino acid transport, intestinal propulsive and gallbladder
      motility, splanchnic blood flow in volunteers and hepatic venous pressure in
      cirrhotic patients. The inhibition occurs to various extents depending on the
      target organ. This review deals with the pharmacological effects of octreotide on
      different gastrointestinal functions and describes the therapeutic role in
      different gastrointestinal disorders.

PMID- 19864764
TI  - Susceptibility of helicobacter pylori to metronidazole and its bioactive
      derivatives.
AB  - The hydroxy derivative of metronidazole can exhibit equal or greater activity to
      the parent drug against several bacteria. The susceptibility status of 22 H.
      pylori strains to these breakdown compounds was determined in order to determine
      their possible role in the therapy of H. pylori associated peptic ulcer disease.
      The susceptibility was determined using the agar dilution method and substantial
      activity (MIC90 = 0.33 .tg/ml) for the hydroxy metabolite of metronidazole versus
      H. pylori was observed. The findings define a role for the hydroxy derivative of
      metronidazole in peptic ulcer disease and support the limited data on the
      possibility of cooperative interactions between the parent compound, its main
      derivatives and related companion drugs in this condition.

PMID- 19864765
TI  - Symptomatic gallstones: a disease of young Saudi women.
AB  - This is a study performed to identify the risk factors for gallstones in Saudis,
      taking the patient population of King Khalid University Hospital as a sample.
      Only Saudis with symptomatic gallstones were studied, the parameters being age,
      sex, weight, body mass index, fertility, age at menarche and age at marriage. The
      results showed that sex, weight, body mass index and fertility all appeared to be
      important factors in the development of gallstones and that the condition affects
      more Saudi females and at a younger age than reported in the literature, probably
      due to overweight and factors related to reproductivity. We conclude that
      gallstones are common in Saudi women and affect them at a younger age than
      western women, weight and fertility appear to be important risk factors.

PMID- 19864766
TI  - Laparoscopic cholecystectomy for acute cholecystitis.
AB  - One hundred and eight patients with histopathologically confirmed acute
      cholecystitis underwent laparoscopic or attempted laparoscopic cholecystectomy in
      the Security Forces Hospital, from October 1991 to April 1996 were
      retrospectively reviewed. All the patients had routine laboratory works including
      abdominal ultrasonography. Females represented 75% and 57% had previous
      admission. Diabetes mellitus was found in 43.5%. Laparoscopic cholecystectomy was
      successfully completed in 71.2%. The main reasons for conversion in 31 patients
      were adhesions and unclear anatomy in 87%. The mean operative time was 96
      minutes. Laparoscopic cholecystectomy for acute cholecystitis can be a safe and
      effective alternative to open cholecystectomy provided a safe dissection of the
      ductal and vascular anatomy with liberal attitude towards conversion is adopted.
      Patients presenting with leukocytosis> 15,000/mm3, mass or diabetes are the most
      likely to be converted to open surgery.

PMID- 19864767
TI  - Extracorporeal shock wave lithotripsy for the rescue of post-endoscopic or
      surgically retained biliary duct stones: does saline irrigation affect the
      outcome?
AB  - Extracorporeal shock wave lithotripsy (ESWL) has been found valuable in
      situations where obstructing stones in the common bile or intrahepatic ducts are
      retained following surgery or attempted endoscopic removal. However, success
      rates are dependent on the type of ESWL system employed and upon a high frequency
      rate of repeated treatment sessions. We outline our experience with 23 cases of
      retained, obstructing bile duct stones, ranging in size from 10 to 40 mm
      diameter, treated with Dornier HM3 ESWL. In the initial 12 patients in the
      series, successful stone fragmentation occurred in 83% of cases with a median 1.6
      treatment sessions. In the latter 11 cases in the series, patients were treated
      prone and the stone-bearing biliary duct was irrigated with saline solution
      during ESWL delivery. With this technique, successful stone break up was achieved
      in all patients (100%) with a single treatment session. Endoscopic sphincterotomy
      is, however, a prerequisite for extracorporeal lithotripsy and, despite the high
      success rates now available with new techniques, we believe the ESWL should
      continue to be employed in support of primary endoscopic methods of management
      for obstructing bile duct stones.

PMID- 19864768
TI  - Malnutrition among hospitalized patients in King Khalid University Hospital,
      Riyadh.
AB  - The present study was undertaken to determine the incidence of malnutrition among
      hospitalized patients. A cross-sectional study of patients were evaluated for
      findings suggestive of protein calorie malnutrition (PCM). Hundred and sixty
      patients admitted to the medical and surgical wards over a period of five months
      were studied. Anthropometrics and biochemical measurements were used. Nutrition
      status was calculated based on some nutrition parameters weight for height,
      midarm, circumference, serum albumin and total lymphocyte count. Anthropometric
      measurements, weight for height and midarm circumference reflected malnutrition
      (PCM) of 33.8% and 30% respectively. The overall prevalence of obesity was 21%. A
      higher proportion (23.9%) of medical cases were found to be obese compared to
      surgical cases (19.7%). If malnutrition can be documented on hospital admission,
      attempts can be made to reverse malnutrition in the high risk patients.

PMID- 19864769
TI  - Post-partum spontaneous liver rupture: a case report.

PMID- 19864770
TI  - Unusual cause of hematemesis and melena.

PMID- 19864771
TI  - Update on Helicobacter pylori diagnosis and treatment.

PMID- 19864772
TI  - Diagnosis of diseases of biliary and pancreatic ducts with magnetic resonance
      cholangio pancreatography (MRCP).
AB  - Magnetic Resonance Cholangio Pancreatography (MRCP) is a new noninvasive imaging
      technique for the evaluation of bilio-pancreatic disorders. Different sequences,
      using both breth-hold and nonbreath-hold techniques, have been employed in order
      to obtain MRCP images. The authors discuss the technical aspects, particularly
      focusing their attention on a nonbreath-hold, three-dimensional, fat-suppressed
      Turbo Spin Echo sequence, optimised on a 0.5 T magnet with 15 mT/m gradients.
      Clinical applications of MRCP are evaluated, presenting data from both the
      literature and the personal experience. The main indication for MRCP study is
      represented by the evaluation of common bile duct obstruction, with the aim of
      assessing the presence of the obstruction (accuracy: 91-100%) and, subsequently,
      the level (accuracy: 85-100%) and the cause. The utility of associating
      conventional Magnetic Resonance (MR) images to MRCP in malignant strictures, in
      order to characterize and stage the malignant lesion is also discussed. Finally,
      data are presented regarding the indictions and the utility of MR-pancreatography
      in the evaluation of patients with chronic pancreatitis.

PMID- 19864773
TI  - Importance of confirmatory testing in donated blood.
AB  - During the period from January 1995 to January 1996 blood units from 8747 blood
      donors were screened for blood-borne viruses at King Khalid University Hospital,
      Riyadh, Saudi Arabia. These tests included HBsAg, antibodies to hepatitis C virus
      (anti-HCV), antibodies to human immunodeficiency viruses (anti-HIV-1/2). During
      the same period 1500 blood units were screened for antibodies to human T-cell
      lymphotropic virus type 1 (anti-HTLV-1). Among the 8747 blood donors, 2.7% were
      found to be HBsAg-positive on initial screening but 2.2% were confirmed as HBsAg
      positive. Regarding HCV, 2.8% were anti-HCV-positive on initial screening but the
      percentage dropped down to 1.6% on confirmation and only 12 (0.14%) were
      considered indeterminant by line immunoassay. None of the donors was confirmed
      anti-HIV- positive but five were diagnosed as indeterminant by western blot. Only
      four were anti-HTLV- I - positive on initial screening but were diagnosed as
      indeterminant by western blot. In total, 492 (5.6%) of the blood units tested
      were reactive for any one of the four viruses on screening but only 327 (3.7%)
      were confirmed positive. All 492 blood units were not recommended for
      transfusion. This raises the question of the usefulness of confirmatory testing
      in blood donation. We believe the confirmation is only important for counseling
      the donor and a non-reactive result on confirmation should not interfere with the
      decision of not recommending the blood for transfusion.

PMID- 19864774
TI  - Swallowing-induced cardio-respiratory responses in man.
AB  - Swallowing transiently increases heart rate. One of the authors developed
      pronounced bradycardia while breath holding, particularly after an expiration.
      The objective, therefore, was to study his cardiac responses during swallowing as
      pronounced bradycardia developed. When, after a maximum inspiration (supine), the
      heart rate slowly fell below 50 beats min' well-defined P waves (lead II)
      disappeared. By swallowing 6 times on command after the P waves disappeared his
      heart rate increased immediately (68 +/- 1 beats min(-1); n=6). P waves with
      similar morphology to those pre-swallowing were recorded 0.7 +/- 0.1 s (n=6)
      after the first swallow. He continued breath holding after swallowing. P waves
      again disappeared, although at faster heart rates (57 +/- I beats min(-1); n=6).
      Furthermore, well-defined P waves were observed after the second disappearance at
      heart rates within the range 30-40 beats min(-1). Small amplitude P waves
      continued to be recorded from lead I with P wave disappearance in lead II,
      suggesting a pacemaker shift, although not to the av node. Autonomic nerves can
      shift the dominant pacemaker within the sa node. The present report indicates
      that increased vagal tone may be rapidly reversed by swallowing.

PMID- 19864775
TI  - Protective effect of amoxycillin on ethanol-induced gastric lesions in rats.
AB  - Recent studies have suggested that amoxycillin may possess gastroprotective
      effects in addition to its known antimicrobial properties. Therefore, the present
      study was undertaken to investigate the potential gastric protective effects of
      amoxycillin and to determine its possible mechanism(s) of action in rats. Ethanol
      induced gastric mucosal lesions in rats were used as an animal model. Nonprotein
      sulphydryl levels were measured spectrophotometrically. The antioxidant effect of
      amoxycillin was studied by luminol-dependent chemiluminescence technique in
      vitro. Amoxycillin produced marked protection against ethanol-induced gastric
      lesions. The protective effect of amoxycillin was lost by prior treatment with a
      dose of indomethacin that is known to inhibit prostaglandin biosynthesis without
      induction of gastric ulcers. Furthermore, the concentration of nonprotein
      sulphydryls decreased significantly in gastric mucosa after administration of
      ethanol. Treatment with amoxycillin prevented this depletion. Additionally,
      amoxycillin dose-dependently inhibited the phorbol myristate acetate stimulated
      luminol dependent chemiluminescence responses of isolated human polymorphonuclear
      leukocytes in-vitro. These data indicate that the gastric protection effects of
      amoxycillin against ethanol-induced lesions may include generation of mucosal
      prostaglandins, prevention of nonprotein of sulphydryl depletion and antioxidant
      properties.

PMID- 19864776
TI  - Superiority of laparoscopic guided needle biopsy over percutaneous blind needle
      biopsy in diagnosing hepatocellular carcinoma associated with cirrhosis.
AB  - This is a retrospective study of 40 patients clinically suspected of having
      hepatocellular carcinoma. Group 1 (20) patients underwent laparoscopic Tru-cut
      needle liver biopsy and Group II (20 patients) underwent percutaneous blind
      needle liver biopsy. In the first group, in 17 (85%) of the patients, the
      diagnosis of hepatocellular carcinoma was confirmed by histopathology, direct
      observation of cirrhosis was seen in 8 (40%) patients, histopathology
      confirmation of cirrhosis was documented in 6 (35%) patients. In the second
      group, 14 (70%) of the patients were confirmed to have hepatocellular carcinoma
      histopathologically and no patients confirmed to have cirrhosis. Both procedures
      were safe. While ascitic leak from the infraumbilical incision was the only
      complication encountered in the 1st group, no complications were encountered in
      the 2nd group. The results support the premise that laparoscopy directed cutting
      needle biopsy is superior over other techniques in fulfilling all the diagnostic
      requirements for hepatocelullar carcinoma and associated liver cirrhosis which is
      important for surgical liver resection.

PMID- 19864777
TI  - Pneumatosis cystoides intestinales: a forgotten entity.

PMID- 19864778
TI  - Treatment of acute pancreatitis.
AB  - There is no specific treatment for acute pancreatitis. Majority of patients with
      acute pancreatitis respond to medical therapy. Supportive measures and close
      observations represent the cornerstone of the medical therapy. Failure to respond
      to medical treatment may indicate choledocholithiasis or infected necrosis.
      Endoscopic papillotomy with stone retrieval is beneficial in patients with severe
      biliary pancreatitis. Image-guided fine needle aspiration and bacteriological
      examination of aspirate is reliable in detecting infection and deliniating
      causative pathogen. Surgical debridement is the method of choice for treatment of
      infected necrosis. In contrast, in pancreatic abscess, surgery is preserved for
      those, who do not respond to percutaneous drainage combined with antibiotics. The
      benefit of antisecretory and antiproteolytic agents is debatable. A combination
      of antioxidants, calcium channel antagonists and antibiotics may play a major
      role in the treatment of acute pancreatitis in the future.

PMID- 19864779
TI  - Hepatobiliary scintigraphy in the distinction between biliary hypoplasia and
      biliary atresia.
AB  - The aim of this work is to see whether distinction between biliary atresia and
      biliary hypoplasia is possible or not and to present the value and usefulness of
      hepatobiliary scintigraphy in the investigation of infants with persistent
      hyperbilirubinemia. Seventy-seven patients of the age between five days and six
      months (average 62 days), 43 females and 34 males of which 65 Saudi, and 12 non
      Saudis were investigated. Laboratory tests, abdominal ultrasound, hepatobiliary
      scintigraphy, liver biopsy, explorative laparatomy and intraoperative
      cholangiography were performed whenever indicated. The findings on hepatobiliary
      scintigraphy of nonvisualization of the gallbladder and no activity in the bowel
      upto 24 hours post injection were considered consistent with the diagnosis of
      biliary atresia. Minimal bowel activity, or visualization of the gallbladder
      where consistent with biliary hypoplasia. In addition, the liver in the two
      entities appeared in a different shape and can be used as an additional
      distinctive feature. Thirty-four infants were diagnosed by hepatobiliary
      scintigraphy as having biliary atresia. Only 3 of the 34 were false positives as
      compared to cholangiogram and liver biopsy results. Five cases were biliary
      hypoplasia. Hepatobiliary scintigraphy in infants with persistent
      hyperbilirubinemia can be distinguished between BA and BH in a simple and
      noninvasive approach.

PMID- 19864780
TI  - Helicobacter pylori in the dental plaque of healthy Saudis.
AB  - The objective of this study is to determine the presence of Helicobacter pylori
      in the dental plaque of healthy Saudis and its relation to dental care. One
      hundred randomly selected healthy Saudis attending the dental clinic were
      assessed for oral hygiene and periodontal disease by dental examination.
      Information about the use of toothpaste, chewing stick, smoking and dentures was
      obtained. Samples of dental plaque were collected after scoring it according to
      the plaque index. Presence of H. pylori in the plaque was sought by a
      commercially available rapid urease test with a sensitivity of 94% and a
      specificity of 100%. The presence of H. pylori was indicated by a positive rapid
      urease test in 81 %. There was significant correlation of heavy dental plaque
      (plaque index score 3) with presence of H. pylori (p=0.03). We conclude that H.
      pylori is present in the dental plaque of most Saudis and this is due to poor
      oral hygiene.

PMID- 19864781
TI  - Seasonal variation in the incidence of endoscopically diagnosed duodenal ulcer in
      Sudan.
AB  - The seasonal pattern of endoscopically diagnosed duodenal ulcer disease in an
      endoscopy unit in Suba University Hospital and Ibn Sina Hospital, Sudan, was
      evaluated retrospectively for the period 1980-1988. We reviewed all the 12443
      endoscopy records and found 1348 cases of duodenal ulcers. The incidence of
      duodenal ulcer was then calculated for each month separately. We found that in
      Sudan the frequency of duodenal ulcer is significantly higher during winter
      (January-February), and significantly lower during summer (May-August).

PMID- 19864782
TI  - Doxycline-induced esophageal ulcerations.
AB  - Over a period of six years 16 patients presented to Dr. Al Mofarreh's polyclinic
      with drug--induced esophageal ulcerations. One patient had esophagitis without
      ulcerations and two patients, who declined endoscopy were not included in this
      analyzis. The mean age of the remaining 13 patients was 28.92 +/- 10.39 years.
      The mean ulcers number was 3.69 +/- 2.76. The ulcers were located at the mid
      esophagus, 29.23 +/- 3.94 cm from the incisors teeth. Odynophagea, retrosternal
      pain and dysphagea in 13 (100%), 12 (92%) and 9 (69%) patients, respectively,
      were the most frequent presenting symptoms. All patients took a doxycycline
      preparation at bed time with little water. The mean elapse between the drug
      intake and endoscopy was 7.85 +/- 9.96 days. The symptoms resolved within a
      maximum of one week of antireflux treatment despite the continuation of
      doxycycline therapy in three patients with brucellosis. The current data
      confirmed the role of oral doxycycline intake, the timing and the amount of
      concurrent fluid in the etiology of esophageal ulcerations.

PMID- 19864783
TI  - Foods and food allergy: the prevalence of IgE antibodies specific for food
      allergens in Saudi patients.
AB  - OBJECTIVE: The intent of this study is to determine the prevalence and pattern of
      sensitivity to food allergens in Saudi patients. SUBJECTS: The subjects included
      in this study were 58 patients with asthma, 47 patients with rhinitis and 112
      patients with urticaria. They all gave clinical history suspecting food as
      causing or aggravating their symptoms. METHODS: Specific IgE antibodies to
      different food allergens were measured in the patients serum by using the
      Pharmacia CAP Radioaller gosorbent (RAST) Fluoroimmunoassay (FEIA) test. RESULTS:
      IgE-antibodies specific for different foods were detected in 38 (17.5%) out of
      217 patients. Most positive reactions were detected in urticaria patients (9.7%)
      followed by asthmatic patients (5.5%) and allergic rhinitis (2.3%). Reactions to
      peanut (22.6%), egg white (14.5) and cow's milk (12.9%) were very prominent.
      CONCLUSION: The prevalence rate of food allergy seems to be high in Saudi
      patients when compared to studies from other regions. The pattern of food
      reactions, detected in this study, can be utilized in diagnosis of patients with
      suspected food allergy. Further studies will be required to obtain more
      information about the prevalence and incidence rates among different patient
      groups.

PMID- 19864784
TI  - Appendiceal adenocarcinoma simulating primary bladder carcinoma: a case report
      and review of the literature.

PMID- 19864785
TI  - Cerebral venous thrombosis as a complication of ulcerative colitis associated
      with protein-S deficiency: case report and review of literature.

PMID- 19864786
TI  - Peer review and refereeing in medicine and medical sciences.
AB  - Every academic scientist will come into contact with peer review process either
      as a reviewer of others work, or as an author whose work is being reviewed by
      others, or as an applicant for research grant. Historically, peer review process
      came at various times to various journals for a variety of reasons in haphazard
      manner. Many forms of criticisms have been made against the process of peer
      review, and some critics do not believe that the process prevents the publication
      of flawed articles and fraudulent research. Despite the criticisms, there are
      advantages of peer review. At present in medical journalism peer review process
      is an indispensable entity for assessing manuscripts intended for publication.

PMID- 19864787
TI  - Acute pancreatitis.
AB  - The past few years have witnessed a tremendous progress in our knowledge
      regarding the pathogenesis, diagnosis, prognostic evaluation and classification
      of acute pancreatitis. The role of ischemia, lysosomal enzymes, oxygen free
      radicals, polymorphnuclear cells-byproducts and inflammatory mediators in the
      pathogenesis of pancreatic necrosis and multiple organ failure has been
      emphasized. Furthermore, the recent knowledge about agents infecting pancreatic
      necrosis, routes of infection, bacteriological examination of fine needle
      aspirate and appropriate antibiotics have changed the concept of acute
      pancreatitis. New diagnostic tests such as rapid urinary trypsinogen-2 test and
      inflammatory mediators including polymorphnuclear elastase, C-reactive protein
      and interleukin-6 contribute to early diagnosis, prognostic evaluation and
      initiation of an appropriate therapy.

PMID- 19864788
TI  - Pattern of Helicobacter pylori sensitivity to various antimicrobial agents.
AB  - To evaluate the pattern of Helicobacter pylori ( H. pylori ) susceptibility to
      different antimicrobial agents, we prospectively studied 45 H. pylori isolates by
      disc diffusion method. These isolates were obtained from patients aged between 16
      75 years, of both sexes who had no prior history of metronidazole ingestion. A
      total of 45 patients were included, of which 36 were males with a mean age of
      42.9 years and nine females with a mean age of 36.4 years, 62% of patients were
      Saudis. Almost all the H. pylori isolates were susceptible to clarithromycin,
      penicillin, erythromycin, ampicillin, tetracycline, clindamycin and cephradine.
      However, 64.4% of the isolates were resistant to metronidazole. No significant
      difference was found either in susceptibility of isolates from Saudi, non-Saudi
      or male and female patients.

PMID- 19864789
TI  - Selenium protects against ischemia-reperfusion-induced gastric lesions in rats.
AB  - Recent studies have shown that selenium afforded protection against ethanol and
      stress-induced gastric lesions in rats. The present study was undertaken to
      investigate the effect of selenium on ischemia-reperfusion-induced gastric
      injuries in which rats were subjected to 30 minutes of ischemia in the presence
      of 100 mM HCI and a reperfusion for 60 minutes duration. Intraluminal bleeding
      was assessed macroscopically and gastric lesions were graded microscopically
      under an inverted microscope. Nonprotein sulphydryl levels were measured
      spectrophotometrically. The severity of gastric lesions, intraluminal bleeding as
      well as the depletion of nonprotein sulphydryls during the reperfusion periods
      was significantly different from that of control. Pretreatment with selenium
      (0.125-2.0 mg/kg, intraperitoneally) 30 minutes before the ischemia-reperfusion,
      dose-dependently attenuated the gastric lesions, reduced the severity of
      intraluminal bleeding and prevented the depletion of nonprotein sulphydryls in
      the stomach. These results suggest that the gastric protection effect of selenium
      may be due to its antioxidant properties. Furthermore, endogenous nonprotein
      sulphydryls may play a significant role in the protective mechanisms of selenium.

PMID- 19864790
TI  - Impact of open access endoscopy on early diagnosis, treatment and
      gastrointestinal radiology service.
AB  - The objective is to compare the endoscopic findings before and after initiation
      of open access and its effect on gastrointestinal radiology services. The data of
      endoscopic findings before open access endoscopy (July, 1989-June, 1992) and
      after open access endoscopy (July, 1992-June, 1995) was collected from the
      records of the endoscopy unit. Similarly, data of barium meals for the same
      periods was collected from the radiology department. An X2 test was used to
      compare the endoscopic findings before and after open access policy. It is found
      that open access endoscopy increased the workload in the endoscopy unit but at
      the same time reduced the number of gastrointestinal radiological procedures. It
      reduced the waiting period for endoscopy and this helped in making early
      diagnosis and initiation of appropriate treatment.

PMID- 19864791
TI  - CT and barium features of gastrointestinal and peritoneal tuberculosis.
AB  - The radiological features in barium gastrointestinal studies and computed
      tomographic (CT) examinations of 22 consecutive cases of proven peritoneal and/or
      intestinal tuberculosis were analyzed in order to highlight the radiological
      features which could provide ready identification of the disease. There were 15
      cases of intestinal tuberculosis and 7 cases of peritoneal tuberculosis and 3
      patients had both. The commonest location of intestinal tuberculosis was the
      ileocecal region (N=10) which occurred in association with colonic or ilea]
      disease. Bowel wall thickening in CT was largely asymmetrical but minimal and
      symmetrical wall thickening occurred with peritonitis. Luminal narrowing with or
      without mucosal tethering were seen in both CT and Barium studies. Peritoneal TB
      had either high density ascites with smudge or nodular omental surface with a
      thickened omental lining. Also detected was fibrinous dry peritonitis with
      thickened mesenteric tissue. Lymphadenopathy in the peripancreatic, mesenteric or
      paracaval were common to both intestinal or peritoneal tuberculosis (21 out of
      22). Fifty percent of the patients showed some lymph nodes with necrotic centers.
      The differential diagnosis included malignant peritonitis and intestinal or
      mesenteric carcinoid. The study shows that a combination of barium
      gastrointestinal study and computed tomography can provide distinct features
      which could strongly suggest the diagnosis of intestinal or peritoneal
      tuberculosis.

PMID- 19864792
TI  - Hydatid cyst disease (Echinococcus granulosus): experience at Asir Central
      Hospital.
AB  - In a six-year period, starting from the commissioning of Asir Central Hospital in
      1408 H (1988), 43 cases of hydatid cyst disease caused by echinococcus granulosus
      seen in Asir Central Hospital were studied. The pattern was not significantly
      different from other workers' experiences. There was equal sex distribution and
      the average age was 41.7 years. The clinical presentations depended essentially
      on the organs affected, and computed tomography usually confirmed the diagnosis.
      The serological test at times gave a false negative result. Most of the patients
      came from Abha in Asir region and the most commonly involved organ was the right
      lobe of the liver. All the patients had laparotomy, excision or incision and
      drainage of the cyst, depending on whether the cyst could be safely excised or
      only drained. The average hospital stay was 17 days. We believe that surgical
      intervention should be the first line of treatment especially when the cyst is
      large.

PMID- 19864793
TI  - Adenomyomatosis--a case report.

PMID- 19864794
TI  - Meckel diverticulum presenting as an abdominal mass.

PMID- 19864795
TI  - Pediatric liver transplantation.
AB  - Pediatric liver transplantation has become a widely accepted therapy for children
      with end-stage liver disease. The objectives of this article are to review the
      development of liver transplantation in children, provide an overview of
      indications and complications, examine some of the exciting technical advances
      made over the last decade that have improved donor organ availability for
      children, look at some of the technical problems that still need to be solved,
      discuss current outcomes and outline new directions of research.

PMID- 19864796
TI  - Primary prophylaxis for bleeding from esophageal varices.
AB  - Esophageal varices develop in 30-70% of patients with liver cirrhosis. One-third
      of these varices will eventually bleed and first episode could be fatal in 40-50%
      of patients. Because of this, primary prophylaxis can be justified if patients at
      high risk of bleeding can be identified. Many endoscopic findings can identify
      the patients likely to bleed in near future. The results of primary prophylaxis
      with portacaval shunts and endoscopic sclerotherapy have been disappointing.
      Nonselective betablockers have been found effective in preventing bleeding from
      varices and their use is justified for this purpose.

PMID- 19864797
TI  - Schistosomiasis as a possible risk factor for acquiring hepatitis C virus (HCV)
      infection among Saudis.
AB  - BACKGROUND: Risk factors for acquiring hepatitis C virus (HCV) infection have
      been elucidated in many developed countries but the picture is still not clear in
      many Middle Eastern Countries including Saudi Arabia. AIM: To investigate
      possible risk factors for acquiring HCV among Saudis. METHODS: Various
      demographic and medical risk factors that might be associated with the spread of
      HCV among Saudis were investigated. The population studied included 20 anti-HCV
      positive with chronic liver disease (CLD), 30 anti-HCV-positive patients without
      CLD and 272 anti-HCV-negative Saudi blood donors. All people investigated were of
      the same age group (>40 years of age). RESULTS: None of the demographic
      parameters studied (type of job, type of housing, education) was found to be
      significantly associated with acquiring HCV infection among our Saudi patients.
      On the other hand up to 40% of the anti-HCV-positive patients and irrespective of
      the condition of liver disease had a history of surgery, and 25% of them had a
      history of multiple injections. Furthermore, at least 20% of our anti-HCV
      positive patients had a history of schistosomiasis which is significantly higher
      than schistosomiasis among the blood donors (P < 0.005). CONCLUSION: In addition
      to blood and blood products, schistosomiasis seems to be a possible risk factor
      for acquiring HCV among the Saudi population. The association between
      schistosomiasis and enhancement of HCV infection need to be further elucidated.

PMID- 19864798
TI  - Hepatobiliary scintigraphy in the diagnosis of choledochal cysts in children.
AB  - The objective is to present the usefulness of hepatobiliary scintigraphy in the
      investigation of children with suspected choledochal cysts through our experience
      in King Khalid University Hospital at King Saud University, Riyadh. Seven
      patients aged between I and 10 years (average 4.8 yrs) comprising six females and
      one male were investigated. Laboratory tests, abdominal Ultrasound and/or CT, and
      cholangiography were performed whenever indicated. Persistent activity in a
      dilated common bile duct, with or without dilatation of intrahepatic bile ducts,
      was considered a positive indicator for choledochal cyst disease. Four children
      with cystic dilatation (type I) were diagnosed by hepatobiliary scintigraphy, one
      saccular (type II), and two cases of Caroli's disease (type V). The diagnosis of
      choledochal cyst was proven by surgery with histological confirmation.
      Visualization of the gallbladder occurred in one case only. The common bile duct
      was seen in four cases. Late activity in the bowel was noted in two cases.

PMID- 19864799
TI  - Life event stress in duodenal ulcer compared with functional dyspepsia: a case
      control study.
AB  - This is a prospective study of life event stress in 80 duodenal ulcer patients
      compared with 80 patients with functional dyspepsia and 80 healthy controls;
      matched for age, sex and marital status. A semi structured psychiatric interview
      was used in the psychiatric assessment of the dyspeptic patients and controls. A
      modified version of Life Events Scale by Tennant and Andrews was used in the
      assessment of life event stress. More dyspeptic patients reported life events
      than the controls, but, on the whole, the differences were not statistically
      significant. On the other hand, more patients with functional dyspepsia
      experienced life events than the patients with duodenal ulcer, but again the
      results were not consistent. Life event stress as measured by the experience of
      undesirable life events was significantly reported by more patients with
      functional dyspepsia. The significance of the presence of life events in duodenal
      ulcer and functional dyspepsia patients is not substantiated in the present
      study, as the positive findings were few and sometimes inconsistent. More
      quantitative studies are needed, taking into consideration the other aspects of
      the problem like personality, cognition and the complex interaction of stressors
      and personality.

PMID- 19864800
TI  - Perforated duodenal ulcer in Asir central hospital.
AB  - In a study of 27 cases of perforated duodenal ulcer seen at Asir Central Hospital
      over a period of seven years, two patients were females and 25 males. The highest
      incidence was in the fourth decade and the average age was 36.3 years. The Saudi
      foreigner ratio was 1:2.9 in an area where the Saudi-foreigner population ratio
      was 1:3. Nine patients (33.3%) were previously diagnosed as having peptic ulcer
      and had received treatment at one time or the other before perforation. Eighteen
      patients (66.7%) were first diagnosed to peptic ulcer after the perforation. All
      the identified perforations were located anteriorly and anterosuperiorly. Only
      one case occurred in the second part of duodenum. The rest occurred in the first
      part. Two patients were treated successfully conservatively. The month
      perforations occurred most was the month of Shaaban. The fasting period during
      the month of Ramadhan did not show any increase in the prevalence of perforation
      in this hospital.

PMID- 19864801
TI  - Hemorrhoids! Don't call the surgeon yet.
AB  - Two hundred and twenty-four consecutive patients seen for the first time with
      symptomatic hemorrhoids were given a high fiber diet supplemented by ispaghula
      husk. Patients were seen at 1, 3, 6 and 12 months and showed improvement. The
      results suggest that conservative treatment using only a high fiber diet
      supplemented by Metamucil is highly effective in the symptomatic treatment of
      patients with piles.

PMID- 19864802
TI  - Tuberculous enteritis with 21 intestinal perforations: a case report.

PMID- 19864803
TI  - Intussuscepted inverted meckel diverticulum: a case report.

PMID- 19864804
TI  - Ano-rectal foreign body: a case report.

PMID- 19864805
TI  - The Saudi Journal of Gastroenterology: recognition and indexing.

PMID- 19864806
TI  - Vasoactive drugs in the management of acute variceal bleeding.
AB  - Several methods have been used to treat acute variceal hemorrhage. Sclerotherapy
      is the method of choice. The use of vasoactive drugs is popular despite
      unsatisfactory effect and systemic hemodynamic adverse effects. The recently
      introduced longacting somatostatin analogue, octreotide, is more effective and
      has no systemic adverse effects. It may be used while waiting for emergency
      sclerotherapy or in combination with sclerotherapy in patients with high risk of
      rebleeding.

PMID- 19864807
TI  - Fulminant hepatic failure.
AB  - Fulminant hepatic failure is a devastating disease occurring as a complication of
      various forms of liver diseases in both children and adults. The objectives of
      this article is to update the knowledge of physicians, on the most important and
      recent advances related to this condition with the ultimate goal of improving
      patient care.

PMID- 19864808
TI  - Audit of laparoscopic cholecystectomies in a district general hospital.
AB  - Laparoscopic cholecystectomy was first performed in Buraydah Central Hospital, Al
      Qassim in September 1993. Since more than 125 open cholecystectomies were
      performed annually, there was a need to be able to deliver this type of service
      to the patients in our hospital. Continued audit is needed to ensure that the
      results with low complication rates achieved in tertiary centers are reproduced
      by the surgeons at district level. Our study of 340 laparoscopic
      cholecystectomies performed between September 21, 1993 and September 20, 1995
      describes the results with incidence of complications, conversion to open
      procedure, mean operation time and the extend of postoperative stay in a district
      hospital. Our complication rates compare favorably with the results achieved in
      laparoscopic cholecystectomy in many centers. Data obtained by us suggests that
      laparoscopic cholecystectomy is safe and effective for the treatment of
      cholecystitis, and this technique can be introduced safely in a district general
      hospital in Saudi Arabia.

PMID- 19864809
TI  - Parasitic disease of the liver and biliary tree.
AB  - Several parasites infest liver or biliary tree, either during their maturation
      stages or as adult worms. Bile iry tree parasites may cause pancreatitis,
      cholecystitis, biliary tree obstruction, recurrent cholangitis, biliary tree
      strictures and some may lead to cholangiocarcinoma. This review discusses the
      hepatobiliary parasites, and shows our experience in diagnosis and management of
      these parasites. Ultrasonography of the liver is diagnostic in schistosomiasis,
      hydatid cysts, amebic liver abscess, ascariasis and other biliary tree parasites
      showing bile duct dilatation. Percutaneous aspiration under ultrasonography
      guidance of hydatid liver cysts or amebic abscess are effective measures in
      management. Endoscopic retrograde cholangiopancreatography (ERCP) is safe and
      effective in diagnosis and management of biliary tree parasites.

PMID- 19864810
TI  - Gastroenterological manifestations of sickle cell disease.
AB  - Sickle cell hemoglobinopathy is a common genetic disorder which is prevalent in
      certain areas of the Kingdom of Saudi Arabia. It is characterized by repeated
      hemolytic and vasoocclusive crises which lead to widespread vascular occlusion
      and subsequent multiple organ infarctions. Affected individuals present with a
      wide variety of gastrointestinal disorders mimicking vasoocclusive episodes
      causing diagnostic confusion and delays that may catch the unwary clinician. This
      article briefly reviews the gastroenterological manifestations of sickle cell
      disease.

PMID- 19864811
TI  - Persistent diarrhea as an emerging child health problem.
AB  - Persistent diarrhea (i.e. acute episodes lasting more than 14 days) has been
      recognized by the WHO as a major public health problem in developing countries
      and a research topic of high priority. Persistent diarrhea is often associated
      with malnutrition, growth faltering, and a substantial risk of mortality in
      children below 5 years of age. Reported incidence and case-fatality rates from
      persistent diarrhea vary substantially. Substantial disagreement exists regarding
      definition, incidence and various putative risk factors. Resolution of such
      measurement related problems will allow for an accurate estimate of the force of
      morbidity and mortality from presistent diarrhea, while the elucidation of its
      risk factors will simplify policy making and the tailoring of intervention
      programs.

PMID- 19864812
TI  - Necrotizing enterocolitis, surgical experience.
AB  - Between January 1988 and December 1994, 29 cases of necrotizing enterocolitis
      (NEC) required surgical management. There were 15 males and 14 females. The
      gestational age range was 24-38, average 32.7 weeks and body weight range was 565
      4500 grams, average 1,680 grams. Necrotizing enterocolitis developed within two
      weeks of age in 55% of the cases, between two and four weeks in 34% and beyond
      four weeks in four cases (14%). Pneumoperitoneum was the commonest indication for
      surgery (55%) of cases, followed by failure of response to medical treatment. The
      commonest surgical procedure was resection of the gangrenous bowel with creation
      of an enterostomy for the segmental disease in 15 cases (50%) and resection with
      primary anastomosis in six cases (20%). Four cases (14%) had NEC totalis for
      which drainage alone was done, and two cases had external drainage alone.
      Survival rate was 72%.

PMID- 19864813
TI  - Meckel diverticulum revisited.
AB  - Nine cases of Meckel diverticulum seen over a period of four years are presented.
      Six presented with gangrene, perforation, intestinal obstruction, intraabdominal
      abscess and pain related to Meckel diverticulum. The remaining three were
      incidental findings. Seven of the patients were males and two females. Average
      age of the patients was 25.5 years. The paper reaffirms the well-known practice
      that Meckel diverticulum should be looked for at laparotomies and resected when
      seen.

PMID- 19864814
TI  - Metastatic hepatocellular carcinoma with occult primary: a case report.

PMID- 19864815
TI  - Primary keratinizing squamous cell carcinoma: an exceptional tumor of the
      gallbladder.

PMID- 19864816
TI  - Gastrointestinal bleeding from the jejunal metastatic choriocarcinoma: a case
      report.

PMID- 19864817
TI  - Radiology quiz. Confirmed case of ulcerative colitis.

PMID- 19864818
TI  - Alpha-1-antitrypsin deficiency: an overview of recent advances.
AB  - Alpha1-antitrypsin (alpha1AT), a serpine, is one of the most important proteinase
      inhibitor in the serum and plays an essential role in protection of the lung
      tissues against the proteolytic attach of elastase. The gene for alpha1AT is
      located on chromosome 14 q 32 and is highly susceptible to mutations. A large
      number of variants of alpha1AT are known and some including PiZ and PiS result in
      alpha1AT deficiency. In patients with PiZ, the most severe and common alpha1AT
      deficient variant, the alpha1AT protein accumulates in the liver and results in
      severe hepatic diseases. Other clinical consequences of alpha1AT deficiency
      include emphysema in majority of the patients. This state is further aggravated
      in patients who smoke. Several treatment strategies have been suggested,
      including replacement therapy by purified alpha1AT or recombinant alpha1AT given
      intravenously or as aerosol. Synthetic peptides. lung transplantation and volume
      reduction surgery are under investigation and evaluation. This paper updates the
      information on alpha1 AT and its deficiency state.

PMID- 19864819
TI  - Chronic hepatitis--an update on terminology.
AB  - This is a review on the updated terminology of chronic hepatitis, a topic that
      has gained much popularity in the current literature of gastroenterology. The aim
      of this review is to familiarize readers with its use and to discourage the old
      terminology. The new terminology of chronic hepatitis takes into consideration
      etiology, severity (grade) and degree of chronicity measured by fibrosis (stage).
      The use of the new terminology would standardize our diagnosis with the aim of
      standardizing therapeutic modalities for the purpose of reproducibility of
      results.

PMID- 19864820
TI  - The postcholecystectomy syndrome: a review.
AB  - The objective is to study the Postcholecystectomy Syndrome (PCS); its causes,
      different methods of diagnosis and different treatment options and their results
      in order to deduce from the above data the best method of prevention of its
      occurrence and the best method of treatment once it has occurred. Data sources
      include a medline search of articles covering this topic in the English
      literature and the abstracts of non-English articles from 1966-1994. The total
      number of articles of interest to the study being approximately 120. There are
      many causes of PCS, some related to improper preoperative diagnosis and some
      related to avoidable and unavoidable consequences of cholecystectomy. The
      different diagnostic modalities are dependent on the cause as are the different
      treatment options. The best treatment of this condition remains prevention
      whenever possible. Proper diagnosis of those patients who truly require
      cholecystectomy and care in performing the cholecystectomy will minimize the
      incidence of this syndrome.

PMID- 19864821
TI  - Diagnostic and therapeutic value of ERCP and prediction of outcome: a
      retrospective analysis.
AB  - The objective is to analyze the experience of using diagnostic and therapeutic
      ERCP and to attempt identifying the independent factors that predict positive and
      useful procedures. The medical records of 198 patients seen during the period
      1991-1993 were retrospectively reviewed. There were 102 males and 96 females with
      a mean age of 45.2 SD + 16.7 years. The main indications for performing the
      procedure were jaundice, abdominal pain, nausea and/or fever. Laboratory tests
      showed elevated direct bilirubin in 50% of patients, deranged liver enzymes in
      43%, and ESR was raised in 51% and fever was documented in 52% of patients. The
      cannulation of both ducts was successful in 93% of all procedures. The commonest
      finding was gallbladder and common bile duct stones (CBD). In 54 patients out of
      64 with CBD stones, stones were removed endoscopically. Stepwise regressive
      analyzis has identified age above 40 years, presence of jaundice (total bilirubin
      > 2.5 mg/ml) and raised ESR (> 25 mm in the 1st hour) as significant factors that
      independently predict a positive ERCP that revealed findings previously unknown
      (useful procedure). Diagnostic and therapeutic ERCP is an integral part in
      management of biliary and pancreatic ducts disorders. The validity of clinical
      prediction role should be tested prospectively.

PMID- 19864822
TI  - Gallbladder perforation: an Asir regional experience and limited.
AB  - Acute gallbladder perforation, an infrequent though not uncommon complication of
      Cholelithiasis and acalculus cholecystitis is reviewed using as materials 16 Arab
      patients (6 males and 10 females; one Egyptian and 15 Saudis) with gallbladder
      perforation among 952 patients who had undergone cholecystectomy in Asir Central
      Hospital between 1990 and 1994. The presentation, method of diagnosis and
      treatment modalities are compared with recent literature review findings. Since
      cholecystitis (calculus and acalculus) is a common pathology in Saudi Arabia a
      preoperative awareness of this complication of the disease will improve diagnosis
      and minimize morbidity and mortality of gallbladder perforation.

PMID- 19864823
TI  - Gallbladder stones analyzes, bile and wound cultures in cholelithiasis.
AB  - One hundred and fifty-two consecutive cases of cholelithiasis were studied. The
      gallbladder stones were analyzed to determine the constituents, the bile
      specimens were cultured and correlated with the cultures when wound infection
      occurred. Mixed gallstones were the commonest type (58.5%), pigment stones (27%)
      and cholesterol stones (14.5%). Positive bile cultures were found in 41 patients
      (27%) and Escherichia coli was the commonest organism isolated. The rate of wound
      infection was 14.5% and the most common organism cultured from the wound was
      staphylococcus epidermidis.

PMID- 19864824
TI  - Crohn's disease in Saudi Arabia: a clinicopathological study of 12 cases.
AB  - In this report we present our experience with 12 cases of Crohn's disease out of
      1279 consecutive colorectal biopsies (0.9%), seen during an l 1 years period
      (1983-1994) in a tertiary care teaching hospital. During the period 76 cases (6%)
      of Ulcerative Colitis (UC) were seen. Of the 12 patients with Crohn's disease,
      seven were males and five were females, all Saudi nationals aged 16-39 with a
      median of 23 years, relatively younger than those with UC seen during the same
      period. Recurrent colicky abdominal pain was the striking presenting symptoms in
      all patients, commonly associated with weight loss. The disease involved both
      small and large bowel in eight patients (67%) and the colon alone in one patient.
      Granulomas were seen in seven patients (58%). Surgery was offered for two
      patients and most of the remaining patients were symptomatic on follow up.

PMID- 19864825
TI  - Extrahepatic biliary atresia with hyaline cartilage and multiple congenital
      anomalies: a case report.

PMID- 19864826
TI  - Traumatic pancreatic pseudocyst.

PMID- 19864827
TI  - Schwannoma of the rectum: a case report.

PMID- 19864828
TI  - Palliative treatment of esophageal cancer: new role of endoprosthesis?
AB  - Esophageal endoprostheses are very useful in management of patients with
      esophageal cancer and are the primary therapy for patients with
      esophagorespiratory fistula. In addition, patients with tumors, poorly responsive
      to dilatation or other therapies, will have long-lasting symptomatic relief when
      an endoprosthesis is placed. The available prostheses are discussed, as well as
      the methods of insertion and the relative merits of each. The self- expanding
      metal stents may have advantages over plastic stents.

PMID- 19864829
TI  - The effect of different types of intragastric balloons with and without a
      behavior modification program in morbid obesity.
AB  - Two consecutive and matched groups of morbidly obese patients, i.e. group (1) and
      (2) were selected to be treated with Garren-Edward Bubble (18 patients) and the
      Danish-Ballobe (10 patients), respectively, and according to the American FDA
      criteria. All patients were put on 1000-1200 K. cal diet and given the choice to
      enroll in the behavior modification program (BMP) or not; (15) patients enrolled
      in it (group A) and (13) patients refused (group B). At the end of the treatment
      period (i.e. 3 months group 1; 4 months group 2) the mean loss in the body mass
      index (BMI) for group (1) and (2) were 5.46 +/- 4.6 kg/m(2), and 3.98 +/- 5.5
      kg/m(2) respectively. With insignificant statistical difference (P>1.0). While
      the mean loss in the BMI was 7.17 +/- 4.54 kg/m(2) and 1.85 +/- 0.92 kg/m(2) for
      group A & B respectively. With a very significant statistical difference (P<
      0.01). No major complication was noticed except that in two patients (group 1)
      and four patients (group 2), the ballon had to be removed within the first week
      of insertion due to intolerance. In conclusion, although both balloons are safe,
      they are weakly effective and the main effect could be attributed to the BMP.

PMID- 19864830
TI  - Ulcerative colitis amongst the Saudis: six-year experience from Al-Madinah
      region.
AB  - Ulcerative Colitis is now being recognized amongst the Arabs. After consideration
      of the clinical, endoscopic and histopathological data, 80 Saudi patients out of
      1,182, were diagnosed as ulcerative colitis. There were 47 males and 33 females.
      The age ranged between two and 90 years (mean 36.5 years). Endoscopically, the
      disease was limited to the rectum in 22.5%, rectum and sigmoid in 30%, extended
      up to the splenic flexure in 27.5% and beyond the splenic flexure in 20% of the
      patients. Our data supports the recent observation that ulcerative colitis is not
      uncommon in this part of the world. There are differences in the extent of
      disease and the presence of local complications, between our patients and those
      in the high incidence areas.

PMID- 19864831
TI  - Comparative study of plain abdominal films and small bowel enema in clinically
      unclear cases of small bowel obstruction.
AB  - A study was undertaken to compare the usefulness of plain abdominal X-rays (PABR)
      and small bowel enema (SBE) in evaluating cases of clinically unclear small bowel
      obstruction. The PABR of the patients taken just before the small bowel enema
      were compared to the films of the SBE. Fifty-two out of 76 were eventually
      operated on. The results show the gross limitations of PABR in excluding the
      presence of small bowel obstruction. The sensitivity and negative predictive
      value of SBE in identifying or excluding obstruction were 100% each, while the
      corresponding values of PABR were 42 and 40%. However, the margin of specificity
      and positive predictive values were narrow; 94 and 97 percent in SBE and 86 and
      88 in PABR. SBE was also superior in identifying the cause and location of
      obstruction. In conclusion, due to the specificity of PABR it will remain the
      first line of investigations in suspected intestinal obstruction. However, its
      limitation in excluding the presence of obstruction cannot be overemphasized. The
      SBE confirms or excludes obstruction promptly and should be applied as the most
      accurate evaluation.

PMID- 19864832
TI  - Ascites: tips on diagnosis and management.
AB  - Clinical evaluation and diagnostic paracentesis with estimation of the serum
      ascitic albumin gradient (SAAG) is the most important step in identifying the
      etiology of ascites. At a level of 1.1 g/dl, SAAG, accurately (96.7%)
      differentiate portal hypertension from nonportal hypertension-associated ascites.
      The majority of patients with ascites (>80%) have portal hypertension associated
      etiology mainly, liver cirrhosis. Approximately 90% of patients with ascites
      complicating cirrhosis respond to salt restriction and diuretics. The remainder
      (10%),have refractory ascites which commonly respond well to large volume
      paracentesis (LVP). Asymptomatic complications occurring in patients treated with
      LVP may not necessitate treatment. Other alternative methods for treatment of
      refractory ascites include: ascitic fluid recirculation (AR), peritoneovenous
      shunting (PVS),transjugular intrahepatic portosystemic stent-shunting (TIPS) and
      orthotopic liver transplantation (OLT).

PMID- 19864833
TI  - Hepatic tumors in a Saudi patients population.
AB  - Cytological diagnosis of one hundred and fifteen patients who had fine needle
      aspiration (FNA) of liver masses during the period from January 1987 to December
      1993 was reviewed. Primary hepatocellular carcinoma (HCC) was the most common
      diagnosis in 87 patients (76%) with a male predominance of 82%, HBsAg and HCV
      antibodies were positive in 46 and 62% of patients, respectively. HBcAb was
      positive in 87% of patients. The median alphafetoprotein (AFP) level was 902
      ng/ml. Sixty-two patients had AFP more than 200 ng/ml (normal range up to 8
      ng/ml). Abdominal pain and liver mass were the most common clinical presentations
      in 88 and 90%, respectively. Raised ALT and AST were noted in 78 and 93%,
      respectively. Sixty-two percent of patients had low serum albumin less than 35
      g/L. In conclusion, HCC was the predominant finding in patients presenting with
      liver mass. HCV antibodies were frequently associated with HCC. AFP of 200 ng/ml
      or more was diagnostic of HCC in those patients and may negate further
      histological confirmation in those who are moribund or have serious coagulation
      disorders.

PMID- 19864834
TI  - Hepatitis C virus infection among maintenance hemodialysis patients: a
      preventable problem of the world.
AB  - Hepatitis C virus (HCV) infection, unrelated to blood transfusion is very common
      among hemodialysis patients with chronic renal failure. The positivity rate for
      anti-HCV varies from 18% to 91% among various countries. It is due not only to
      the past blood transfusions, but also to nosocomial transmission which is
      preventable. The main route of virus entry, is most likely, the two (arterial and
      venous) needle holes that are touched by the fingers of the physician and the
      nurse repeatedly. The recommended preventive measures include: the use of a
      sterile glove, finger sterilization with a disinfectant solution, immediately
      before touching the needle/needle hole. and repeated education of the staff.
      Whether the anti-HCV positive patients should be separated from the negative,
      largely depends on the prevalence of HCV infection within the dialysis unit.

PMID- 19864835
TI  - Iron nutrition in infancy.
AB  - Iron deficiency and anemia remain significant health problems worldwide. These
      may he associated with developmental delay and poor mental development. A source
      of exogenous iron, is therefore, advisable after four to five months of age for
      breast-fed babies. Artificially-fed infants should be given iron-fortified
      formula from birth.

PMID- 19864836
TI  - The nutritional management of acute diarrhea.
AB  - Acute diarrhea may have a profound effect on nutritional status worldwide. After
      rehydration, proper nutritional management can mitigate these effects. This paper
      discusses the advantages and disadvantages of continued feeding, emphasizing that
      breastfeeding should not be stopped during episodes of acute diarrhea.

PMID- 19864837
TI  - Pattern of pediatric upper gastrointestinal disease: a teaching hospital
      experience.
AB  - During the period 1983-1993, 166 pediatric patients(91 females and 75 males) were
      subjected to upper gastrointestinal endoscopy. Epigastric pain or heart burn and
      vomiting were the indications in 115 (69%) patients. Gastritis. duodenitis, and
      esophagitis were diagnosed in 63 (38%), and duodenal ulcer in seven (4.2%)
      patients. Bleeding sites were identified in 10 out of 21 (47.6%) patients with a
      history of hematemesis. Helicobacter pylori was identified in 12 (48%) of 25
      patients with chronic gastritis. Endoscopic removal of foreign bodies (FB) was
      required in nine patients. Endoscopic small bowel biopsy provided sufficient
      material to con-firm the diagnosis in seven out of 13 patients with chronic
      diarrhea. Endoscopic findings were normal in 78 (47%) patients. The procedure was
      safe and well tolerated.

PMID- 19864838
TI  - Role of oxygen-derived free radicals on gastric mucosal injury induced by
      ischemia-reperfusion.
AB  - A free radical is an unstable and highly-reactive chemical species capable of
      independent existence that contained one or more unpaired electrons in its outer
      orbital. A number of oxygen-derived free radicals (ODFRs) have been identified.
      However, superoxide (O(-)(2) and hydroxyl (OH*) radicals are extensively studied.
      The univalent reduction of oxygen to water produces a number of highly-reactive
      chemical intermediates such as O(-)2 and OH*, which are commonly-known as oxygen
      derived free radicals. ODFRS may be formed from several sources as follows: a)
      mitochondrial cytochrome oxidase, b) xanthine oxidase, c) neutrophils and d)
      transitional metals. There are several important defense mechanisms to limit or
      to prevent the damage caused by excessive ODFRs activity. These antioxidant
      defenses can be divided into a) enzymatic defense mechanisms such as: superoxide
      dismutase (SOD): catalase: selenium-containing glutathione peroxidase and b) non
      enzymatic defense mechanisms including: alpha-tocopherol; ascorbic acid;
      glutathione and any sulfhydryl-containing compounds.

PMID- 19864839
TI  - Management of gallstones.
AB  - Asymptomatic patients with gallbladder stones rarely develop complications and
      therefore do not require treatment; in contrary, symptomatic patients should he
      treated. Nowadays, several approaches are available to treat gallbladder and
      ductal stones using surgical techniques. chemical dissolvents, fragmentation,
      endoscopic and percutancous approaches. The choice of approach is influenced by
      the site, size and chemical composition of stone, as well as the age, general
      condition and desire of patient. Surgical approaches are considered as the
      primary method of treatment. Nonsurgical treatment is considered in patients at
      high risk and patients unwilling to undergo surgery. The main concern of non
      surgical treatment is the high recurrence rate, especially after dissolution.

PMID- 19864840
TI  - Fulminant hepatic failure in children.
AB  - Fulminant hepatic failure is a clinical syndrome resulting from massive necrosis
      or severe functional impairment of hepatocytes. This paper reviews the etiology,
      pathogenesis and management of this condition. Orthotopic liver transplantation
      may achieve very high survival rates (50-70%).

PMID- 19864841
TI  - Extrahepatic biliary atresia.
AB  - Extrahepatic biliary atresia is a disease of unknown cause, leading to profound
      cholestasis and progressive biliary cirrhosis. This paper discusses the diagnosis
      and management of this condition. It is stressed that bile flow can be
      established in 80-90% of infants referred to surgery within 60 days after birth.
      Liver transplantation is essential for infants who are referred late (120 days of
      age or later); those whose initial portoenterostomy was not successful, and those
      who develop end-stage liver disease in spite of bile drain-age.

PMID- 19864842
TI  - Pattern of liver disease in a Saudi patient population: a decade of experience at
      security forces hospital, Riyadh, KSA.
AB  - We report the pattern of liver disease revealed by a study of liver biopsies of
      277 adults aged 16-85 years old from January 1983 - December 1993. The most
      common histological diagnoses were: cirrhosis in 22.3%, chronic active hepatitis
      (CAH) 16.6%, hepatocellular carcinoma (HCC) in 7.2%, fatty changes in 12% of
      patients. Less common diagnoses included: Cholestasis in 8 (2.8%),
      Hemochromatosis in 7 (2.5%), periportal fibrosis in 4 (1.4%), Wilson's disease in
      3 (1%), Alcoholic hepatitis in one patient and lymphoma in one patient.
      Inadequate specimens were encountered in 7 (2.5%). The commonest causes of liver
      cirrhosis were: Hepatitis C virus (HCV) in 73.3% of patients tested for it and
      hepatitis B virus (HBV) in 23.2%. Complications related to the procedures were
      exceedingly low. One patient, with Budd-Chiari Syndrome required emergency
      laparotomy to control bleeding. In conclusion, liver cirrhosis, CAH and HCC were
      common patterns of chronic liver disease in this series. HCV was the most common
      cause of CAH and liver cirrhosis.

PMID- 19864843
TI  - Unusual cause of epigastric mass.

PMID- 19864844
TI  - Prognosis and prognostic factors in inflammatory bowel disease.
AB  - The chance of normal survival for patients with inflammatory bowel disease is
      generally good. There may be a small excess mortality for those with Crohn's
      disease; however recent studies do not confirm this trend. For those with
      ulcerative colitis, there may be an excess mortality in the first two years after
      diagnosis, especially in those who undergo surgery. The necessity for an
      operation varies, but at least 50% of patients with Crohn's disease will be an
      operation in the first 10 years; whereas only about 20% of patients with
      ulcerative colitis will require a colectomy. Most patients with inflammatory
      bowel disease are able to lead a normal life and are not disabled by their
      disease. The prognosis in the elderly is usually good; however there is an
      increased mortality over younger patients, which is probably due to the presence
      of coexistent disease. Children also have a slightly higher mortality; this may
      be due to the relative frequency of a particularly extensive disease and the
      development of colorectal cancer. Growth retardation occurs in up to one-third of
      children with Crohn's disease, but it may be resolved if remission can be
      obtained. Pregnancy has not been shown to have an impact on inflammatory bowel
      disease, but its onset during pregnancy confers a significant risk for both
      mother and child. Extensive involvement is a poor prognosis factor in both
      diseases; conversely, isolated small bowel Crohn's disease and ulcerative
      proctitis carry particularly good prognoses. A short clinical history, fistulae
      or abscesses at presentation probably represent an aggressive form of Crohn's
      disease. Hypoalbuminemia, anemia and raised inflammatory markers are laboratory
      markers which suggest a worse prognosis in the short and possibly long-term.

PMID- 19864846
TI  - Diarrhea and malnutrition: a continuing pediatric challenge.
AB  - Acute diarrhea is one of the most prevalent serious health problems in infants
      and children. This article provides an update on diarrhea and malnutrition, with
      particular emphasis on their interactions in pediatric patients.

PMID- 19864845
TI  - Child feeding patterns in the Middle East.
AB  - A diversity in infant feeding patterns exists throughout the Middle East. Wide
      variations in cultures, languages, ethnic background, religions and social
      practices should be taken into consideration, when designing programs to promote
      appropriate feeding practices. Strategies applied in one community might not be
      appropriate for another. In order to be effective, these should be incorporated
      into overall primary health care programs.

PMID- 19864847
TI  - Intractable diarrhea of infancy.
AB  - The current concept of intractable diarrhea of infancy is that of a heterogeneous
      syndrome with diverse etiologies. The purpose of this review is to provide an
      update on this group of dis-eases. As modern diagnostic techniques become
      available, new disorders will continue to be recognized.

PMID- 19864848
TI  - Chronic hepatitis B and C in children.
AB  - Chronic hepatitis B & C represent major medical problems in both adults and
      children. The purpose of this article is to focus on pediatric aspects of these
      two types of viral hepatitis.

PMID- 19864849
TI  - Wilson's disease: a new direction.
AB  - Wilson's disease, first described in 1912, is a familial disease involving copper
      metabolism. This article reviews recent developments in the genetics of the
      disease and their implications for the diagnosis and treatment.

PMID- 19864850
TI  - Spontaneous bacterial peritonitis.
AB  - Spontaneous bacterial peritonitis (SBP) is an infection of the ascitic fluid
      without obvious intra-abdominal source of sepsis; usually complicates advanced
      liver disease. The pathogenesis of the disease is multifactorial: low ascitic
      protein-content, which reflects deficient ascitic fluid complement and hence,
      reduced opsonic activity is thought to be the most important pathogenic factor.
      Frequent and prolonged bacteremia has been considered as another pertinent cause
      of SBP. This disease is associated with high mortality and recurrence. Therefore,
      orompt recognition and institution of therapy and plan of prophylaxis is vital.

PMID- 19864851
TI  - Gallstones.
AB  - Gallstone prevalence is correlated with geographical and ethnic variations. It is
      more prevalent in Western communities. There are evidences for a high prevalence
      in Saudi Arabia. According to their chemical constitutes, stones are classified
      into cholesterol, mixed and pigment stones. Three main factors, saturation,
      gallbladder function and nucleation defect are implemented in the pathogenesis of
      stone formation. Majority of gallstones patients are asymptomatic. Dyspeptic
      symptoms are not specific. Ultrasonography has become the method of choice for
      screening and diagnosis of gallstones. Cholecystoscintigraphy is accurate in the
      diagnosis of acute cholecystitis, biliary obstruction and bile leak. Treatment of
      gallstones will be discussed in the following issue.

PMID- 19864852
TI  - Megacystis-microcolon-intestinal hypoperistalsis syndrome.

PMID- 19864853
TI  - The Saudi Journal of Gastroenterology.

PMID- 19864854
TI  - Nonsurgical cholangioscopy: the present state.

PMID- 19864855
TI  - Chronic diarrhea in children: part II. Clinical approach and management.
AB  - Chronic diarrhea is a complex symptom. The clinical approach and management
      should be based on pathophysiologic considerations and stepwise laboratory
      investigations. In infants with severe malnutrition, nutritional support is a
      priority in the management of this condition.

PMID- 19864856
TI  - Refractory duodenal ulcer.
AB  - Refractory or intractable ulcer is defined as an ulcer that fails to heal
      completely after eight to twelve weeks, despite appropriate treatment with a
      modern antiulcer therapy in a compliant patient. Refractory ulcer should be
      suspected in individuals diagnosed to have peptic ulcer if their symptoms persist
      longer than usual: occurrence of complications or simply their ulcers fail to
      heal, since up to 25% of such patients remain asymptomatic. Conditions associated
      with refractory ulcer include noncompliance, continuous consumption of
      nonsteroidal anti-inflammatory drugs, acid hypersecretion, smoking. male gender
      and other factors with questionable role like advanced age, large ulcer size,
      prolonged duration of symptoms and the presence of complication like bleeding.
      Nonpeptic ulcers like tuberculosis, malignancy, Crohn's disease and primary
      intestinal lymphoma should always be considered in the differential diagnosis.
      Colonization with H. pylori which is well-known as a cause of frequent
      recurrences, has not been linked with refractoriness. Patients with refractory
      ulcers must undergo thorough re-evaluation including repeated endoscopies,
      obtaining biopsies for microbiology and histology and determination of serum
      gastrin level. Once diseases with identifiable etiologies have been ruled out,
      aggressive medical management with single or multiple antiulcer drugs should be
      instituted. Such treatments will virtually heal all refractory ulcers. Surgery
      should be reserved for patients whose ulcers fail to respond to optimal medical
      therapy or those who develop complications necessitating surgical intervention.

PMID- 19864857
TI  - Reduction in the prevalence of antibody to hepatitis A virus among young Saudi
      adults: implications for hepatitis A vaccine.
AB  - Viral etiology was investigated in 133 Saudi patients with acute hepatitis seen
      in King Khalid University Hospital, Riyadh. between July 1993-May 1994. Out of
      the 133 patients, 51 (38.3%) were diagnosed as having acute hepatitis due to
      hepatitis A virus (HAV). Hepatitis C virus (HCV) was the second most common
      etiological agent (20.3%). There were 35 patients with acute hepatitis (26.3%) in
      whom no viral marker for HAV, HBV, HCV, CMV or Epstein-Barr virus (EBV) was
      detected. Among the 51 patients with acute hepatitis due to HAV, the majority
      (88.2%) were children (1-12 years) and only 6 (11.8%) were adults (15-24 years).
      This is in contrast to patients with HCV or HBV infection where the majority were
      adults: 74.1% and 82.3% respectively. The diagnosis of acute hepatitis due to HAV
      in Saudi adults, an observation not seen earlier, indicated a change in the
      epidemiological pattern of HAV infection in the Saudi population. This change was
      confirmed by the significant reduction in the prevalence of anti-HAV in 630 Saudi
      subjects (1-30 years old) (50.2%) investigated in 1994 compared to that of 587
      subjects of the same age group investigated in 1986 (76.5%) (P < 0.005). In the
      light of these results, a nation-wide survey is recommended to confirm this
      pattern in other areas. It is important that high-risk Saudi groups be identified
      and evaluated for their anti-HAV status as these groups are candidates for HAV
      vaccination.

PMID- 19864859
TI  - Gastroenterology in Saudi Arabia.

PMID- 19864858
TI  - Role of ERCP in diagnosis and management of "clip cholangitis": case report and
      review of the literature.

PMID- 19864860
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
AB  - In the 12 years since they were first published "Uniform requirements for
      manuscripts submitted to biomedical journals" (the Vancouver style) have proved
      popular with both authors and editors; over 400 journals have stated that they
      will consier manuscripts that confirm to the requirements and we know that many
      more do so. The fourth edition, published here, incorporation recent amendments
      made by the group.

PMID- 19864861
TI  - Conjugated hyperbilibubinaemia in infancy (infantile cholestasis).
AB  - The finding of high conjugated bilirubin needs prompt evaluation to rule out
      liver or bile duct pathology. If assessment of total and direct bilirubin is
      carried routinely in any infant whose jaundice persists for more than 2 weeks,
      early identification of a group of children who need corrective surgery for
      atresia of the extra hepatic bile duct is possible. The aim of this review is to
      look at common causes of infantile cholestasis with emphasis on evaluation,
      diagnosis, complications, treatment and outcome of infant with neonatal
      cholestasis.

PMID- 19864863
TI  - Gastroesophageal reflux disease.
AB  - In this review of gastroesophageal reflux disease (GERD), we discuss the
      different aspects of physiology and pathophysiology and then the approach to
      diagnosis outlining the advantages and disadvantages of each method. The last
      part of this review covers the management of GERD and advances in this subject
      with special concentration on other aspects of management such as lifestyle
      changes followed by drug management.

PMID- 19864862
TI  - Inflammatory bowel disease: medical management.
AB  - Various papers have been published on inflammatory bowel disease in the Kingdom
      of Saudi Arabia and other Gulf States during last decade. Apparently, the
      published data contradict previous belief and indicate that, we might deal here
      with a medical problem. However, data on the magnitude of this disease in our
      community remains uncertain. Could we attribute this possible change to the
      improvement in diagnostic procedure or to the change in life style?
      Unfortunately, the literature does not provide us with a convicting answer to
      this question yet. However, at this stage a review of the medical management in
      inflammatory bowel disease seems to be justified. Hence currently used drugs in
      the management in inflammatory bowel disease are reviewed in this paper. Some of
      the potentially effective drugs for the future are also summarized.

PMID- 19864864
TI  - Variceal bleeding: management options.
AB  - Portal hypertension with esophageal varices represents an important source of
      upper gastrointestinal bleeding. Variceal bleeding is associated with high
      rebleeding and mortality rates. Various treatment modalities are effective in
      control of bleeding. Endoscopic Sclerotherapy (ES) is the standard method for
      management of acute variceal bleeding alone or in combination with vasoactive
      drugs. Alternative methods are considered in case of sclerotherapy failure.
      Portosystemic shunt operation is complicated by systemic encephalopathy.
      Therefore, it is replaced by other surgical procedures. These include esophageal
      stapled transection, splenectomy with devascularization, distal splenorenal shunt
      (DSRS), DSRS combined with pancreatic disconnection, narrow diameter mesocaval
      (NDMC) or portocaval (NDPC) shunts and liver transplantation. Recently.
      transjugular intrahepatic portosystemic stent-shunting (TIPSS) has been
      introduced in the management of patients with refractory variceal bleeding
      waiting for liver transplantation.

PMID- 19864865
TI  - Endoscopic management of serious non-variceal upper GI bleeding with local
      injection therapy.
AB  - Massive non-variceal upper GI bleeding is a very common and serious problem.
      especially if bleeding comes from a vessel. In these circumstances, unless
      therapeutic endoscopy or emergency surgery is per-formed, the bleeding may lead
      to a very high mortality. Endoscopic injection therapy can be performed by
      injecting diluted epinephrine [1:10,000] or normal saline; alone or with a
      sclerosant. Adding a sclerosant is preferred if the bleeding is massive or has a
      spurt pattern. This technique proved to be highly effective and safe and almost
      comparable to other types of therapeutic endoscopies like bipolar electro
      coagulator (BICAP) heat probe or laser photocoagulation therapy. The clinical
      studies performed in this field, the technique of injection and the types and
      amount of the substance to be injected will be discussed in details.

PMID- 19864866
TI  - Chronic diarrhea in children: part I. Physiology, pathophysiology, etiology.
AB  - Chronic diarrhea is an important cause of morbidity and mortality in children.
      Although the pattern of the problem is well established in Western countries.
      limited data are available from Saudi Arabia. The purpose of this review is to
      provide an updated overview of the physiology of digestion, pathophysiology and
      etiology of diarrhea with particular emphasis on patterns prevalent in Saudi
      Arabia.

PMID- 19864867
TI  - Surgery for appendicular mass.
AB  - Two hundred and seventy-seven patients were admitted with acute appendicitis to
      KKUH during a 5 year period. There were 189 males (68%) and 88 females (32%). Of
      these, 51 patients (18.4%) had appendicular mass diagnosed clinically or under
      anaesthesia. Twenty five were males and twenty six females. All patients with
      appendicular mass underwent exploration and six were found to have abscess
      formation. All patients had their appendix removed. There was no mortality. Three
      patients developed wound infection, one a pelvic collection and one had sub-acute
      intestinal obstruction, giving a complication rate of 9.8%. We feel a surgical
      approach for appendicular mass, in a specialised centre dealing with paediatric
      surgical patients, is a safe alternative to the classical textbook conservative
      approach. It also has the benefit of reducing the hospital stay and requires no
      readmission for interval appendectomy, for which many patients fail to return.

PMID- 19864868
TI  - Biliary fascioliasis clinical spectrum and endoscopic management.
AB  - Human fascioliasis is well documented throughout the world, both the acute and
      chronic phases of the disease have been well described. Cholelithiasis with
      obstructive jaundice and discovery of fasciola hepatica worms during surgical
      exploration is a frequent mode of first diagnosis of chronic fascioliasis. Here
      the presentation of six proven cases are described, all were diagnosed and
      treated by endoscopic retrograde cholangiopancreatography with details of the
      almost characteristic cholangiographic picture that can be hardly be confused
      with anything else, the clinical picture of the cases and their follow up
      together with a review of the disease is discussed.

PMID- 19864869
TI  - A patient with leonine facies and occult lung disease.

PMID- 19864870
TI  - Aging and decision-making: a neurocognitive perspective.
AB  - Neuropsychological research contributes to a better understanding of cognitive
      mechanisms involved in making advantageous decisions, which is important for
      everyday life. Using laboratory gambling tasks, it has been demonstrated that
      both structural and functional brain changes can result in disadvantageous
      decision-making linked to reductions in executive functioning and feedback
      processing. However, relatively little is known about whether or not decision
      making on these tasks is affected by normal aging. We argue that functions
      involved in decision-making - in particular categorization and monitoring
      processes - are most likely reduced in older adults. These reductions should lead
      to decision-making difficulties in older individuals. However, we also argue that
      the effects of age on decision-making depend on the type of decision situation
      (i.e. ambiguous or risky) in combination with the complexity of the decision
      making task. In addition, we give a brief overview of methodological issues that
      should be taken into account in future studies on decision-making and aging.

PMID- 19864871
TI  - Molecular cytogenetic characterization of the human cerebral microvessel
      endothelial cell line hCMEC/D3.
AB  - The immortalized human cerebral microvessel endothelial cell line hCMEC/D3 has
      been repeatedly used as a model of human blood-brain barrier (BBB). hCMEC/D3
      cells between passage 25 and 35 are most often applied in research, remained
      phenotypically nontransformed, and cells maintained many characteristics of human
      brain endothelial cells. Also hCMEC/D3 was thought to have conserved a normal
      diploid karyotype over all these passages. Here we characterized the cell line
      using high-resolution multicolor fluorescence in situ hybridization (FISH)
      approaches and revealed a complex karyotype in the 30th passage. Clonal cryptic
      unbalanced structural rearrangements and numerical aberrations were discovered
      and described as follows: 45 approximately 48,XX, 
      X,del(5)(q11)[2],del(9)(q11)[3],+9[3],del(11)(q13 approximately 14)[2],
      der(14)t(14;21)(q32.33;q22.3)[28],der(15)t(9;15)(p11;p11)[13],
      dup(15)(p11q11)[5],der(21)t(17;21)(p12;q22)[9],-22[6][cp28]. In summary, a
      complex karyotype with clonal unbalanced chromosomal rearrangements is present in
      hCMEC/D3. Thus, we solicit to include molecular cytogenetics in the testing of
      all cell lines prior to application of their use in complex studies.

PMID- 19864872
TI  - Willingness to pay for genetic testing: a study of attitudes in a Canadian
      population.
AB  - BACKGROUND: This article reports results of a 2008 telephone survey of
      approximately 1,200 residents of the Province of Alberta, Canada. The majority of
      respondents reside in urban centers, have some post-secondary education, and
      report annual family income near or above the Canadian average. The goal was to
      explore attitudes and interest regarding different types of genetic tests.
      METHODS: Respondents were asked about their willingness to pay for tests to gain
      information about genetic factors related to manageable conditions, serious,
      unpreventable disease, healthy food choices, psychiatric conditions, going bald
      (asked of men only), and gaining weight. The price categories were CAD 0, CAD 1
      499, CAD 500-1,999 and CAD 2,000+. Respondents were also asked about factors that
      would motivate interest in genetic testing, such as availability of treatment,
      curiosity, and reproductive decision-making. They were also asked if the public
      health insurance system should pay for certain types of tests. RESULTS: Across
      all test categories, few respondents expressed willingness to pay more than CAD
      500 out of their own pocket. 62% stated that the public health insurance system
      should pay for genetic tests for manageable conditions and opinion was divided
      about whether the government should fund tests for serious, unpreventable
      conditions and tests to inform healthy eating choices. CONCLUSION: The principal
      motivator for interest in genetic testing was to learn clinically relevant
      details to inform health-related decisions. Curiosity about genetic risk had only
      a modest impact on consumer interest. In general, younger respondents (18-35
      years) expressed somewhat greater willingness to pay than older respondents,
      especially those 65 and older.

PMID- 19864873
TI  - 'Start the conversation': the New South Wales (Australia) family health history
      campaign.
AB  - BACKGROUND: Evidence that family health history (FHH) informs recommendations for
      appropriate early detection strategies used for the prevention of many health
      conditions underscores the importance of optimizing a patient's knowledge of
      his/her personal FHH. For some conditions, FHH also underpins identifying those
      at potentially high risk for whom genetic testing may be possible and suitable to
      further inform the advice. The Family Health History Campaign 'Start the
      Conversation' was conducted in New South Wales (Australia) in August 2006 as a
      small state-wide media campaign with the aim of encouraging individuals to
      discuss and gather their FHH information about several conditions and report it
      to their doctor. Campaign development included consultations with consumers and
      primary care practitioners (general practitioners - GPs), development of campaign
      resources, and establishment of partnerships. METHODS: Evaluation methodologies
      included community poll surveys pre- and post-campaign, a GP mail survey, and
      website usage analysis. RESULTS: While only 112/403 of the polled community
      reported hearing about the campaign in the media, 48% of those men and women were
      encouraged to start the conversation with their families. Limited findings from
      the GP survey respondents suggested they were engaged, made aware of the
      potential lack of patient knowledge about FHH and generated referral for several
      high-risk patients. CONCLUSION: Campaigns that use the media to encourage the
      community to take action and also engage the GPs can create a supportive
      environment that has the potential to increase the accuracy with reporting of FHH
      to maximize benefit for early detection and prevention.

PMID- 19864874
TI  - Assessing the potential success of cystic fibrosis carrier screening: lessons
      learned from Tay-Sachs disease and beta-thalassemia.
AB  - OBJECTIVE: The objective of this study was to identify factors involved in the
      success of 2 well-established population-based carrier screening programs - Tay
      Sachs disease (TSD) in Ashkenazi Jews and beta-thalassemia in Sardinia and Cyprus
      - and to assess the potential for success of a population-based cystic fibrosis
      (CF) carrier screening strategy using these factors. METHODS: We performed a
      literature review and key informant interviews. RESULTS: Factors involved in the
      success of TSD and beta-thalassemia carrier screening programs include disease
      characteristics (well-defined population at risk, severe disease with predictable
      course, availability of effective treatment), test characteristics (high
      sensitivity, straightforward interpretation of results), and community
      characteristics (involvement of community, support of families and advocacy
      groups, consensus in favor of avoiding affected births). Current CF screening
      strategies include few of the factors listed above. Unlike TSD and beta
      thalassemia, the purpose of current CF carrier screening strategies is informed
      reproductive decision-making, without an explicit goal of reducing disease
      incidence. CONCLUSION: When compared to TSD and beta-thalassemia, CF is a less
      favorable candidate for population-based carrier screening. Because of its
      different purpose, CF carrier screening will require different measures of
      success than those used for TSD and beta-thalassemia carrier screening, and a
      consensus on the value or success of CF carrier screening may be difficult to
      achieve.

PMID- 19864875
TI  - Problems in the regulation of genetic tests in Japan: what can we learn from
      direct-to-consumer genetic tests?
AB  - As one of the countries that have invested greatly in the field of bioscience,
      Japan is facing difficulties introducing human genetic research to the market. A
      key issue is how to regulate the quality of genetic testing. Since genetic
      testing is a part of clinical laboratory tests, the regulatory framework for
      these tests should cover the regulation of genetic testing. Nevertheless, the
      quality of clinical laboratory tests has been regulated largely by the authority
      of medical professionals. The fact that genetic testing can be provided without
      supervision of medical professionals reveals the necessity for the regulation of
      quality of genetic testing. While medical geneticists have publicly criticized
      direct-to-consumer (DTC) genetic testing, a group of industries related to DTC
      genetic testing have established self-regulatory guidelines on the quality
      control of genetic analysis, based on the OECD guidelines. This article describes
      the regulatory framework for clinical laboratory tests including genetic tests,
      and the gaps in regulation, which are particularly highlighted by the appearance
      of DTC genetic testing. Furthermore the current initiatives taken by different
      organizations, especially the self-regulatory initiatives by related industries,
      will be discussed. To conclude the article, recommendations to improve the
      situation will be made.

PMID- 19864877
TI  - Abnormal spermatid formation in the presence of the parasitic B(24) chromosome in
      the grasshopper Eyprepocnemis plorans.
AB  - Morphology and size of spermatids were analysed in the grasshopper Eyprepocnemis
      plorans by means of light and electron microscopy. At light microscopy, normal
      and abnormal (macro- and micro-) spermatids differed in size and number of
      centriolar adjuncts (CAs): 1 CA in normal spermatids and 2 or more CAs, depending
      on ploidy level, in macrospermatids. Males carrying the additional B(24)
      chromosome showed significantly more macro- and microspermatids than 0B males.
      The frequency of macro- and microspermatids showed an odd-even pattern in respect
      to the number of B chromosomes, with a higher frequency of abnormal spermatids
      associated with odd B numbers. Transmission electron microscopy showed that
      macrospermatids carried more than one axoneme, depending on ploidy level: 2 for
      diploid, 3 for triploid, and 4 for tetraploid spermatids. In 0B males, the most
      frequent abnormal spermatids were diploid, whereas in 1B males they were the
      tetraploid spermatids and, to a lesser extent, triploid ones. This suggests that
      most macrospermatids derived from cytokinesis failure and nucleus restitution.
      The implications of aberrant spermatids on B chromosome transmission and male
      fertility are discussed.

PMID- 19864876
TI  - Twin pregnancy presenting as a praevia complete hydatidiform mole and coexisting
      fetus complicated by a placental abscess.
AB  - BACKGROUND: A twin pregnancy consisting of a complete hydatidiform mole and a
      coexisting normal fetus (CMCF) is a rare and challenging condition when diagnosed
      prenatally and is associated with major obstetric complications. CASE REPORT: We
      present a case of CMCF in which the molar component presented as a major placenta
      praevia at 19 weeks, and which was complicated by a placental abscess with
      maternal septicaemia from 26 weeks. An emergency caesarean section, performed at
      28 weeks' gestation due to severe maternal septicaemia, resulted in the delivery
      of a live male infant. Despite the molar mass being praevia, the delivery was not
      complicated by extensive haemorrhage. CONCLUSION: This is only the second case of
      CMCF complicated by a molar praevia and the first complicated by a placental
      abscess. We believe that the 2 conditions are linked and that the absence of
      normal fetal membranes surrounding the molar mass enabled secondary colonization
      by vaginal bacteria. Therefore, we recommend that immediate antibiotic treatment
      is initiated in cases of CMCF presenting as a praevia when maternal and/or fetal
      symptoms of infection develop.

PMID- 19864878
TI  - A case of ovine female XY sex reversal syndrome not related to anomalies in the
      sex-determining region Y (SRY).
AB  - The human XY gonadal sex reversal is a rare disease. Primary amenorrhea, lack of
      secondary sexual characteristics and the possible existence of streak gonads are
      the most common signs of this syndrome. Five cases of this syndrome have been
      described in the last 42 years in bovines. However, to the knowledge of the
      authors, no similar descriptions are available in sheep. In the present report,
      we are presenting the case of a 4 year old ewe 2n = 54,XY showing primary
      sterility and total absence of masculinization signs. The promoter and the
      complete coding segment of the sex determining region Y (SRY) were sequenced and
      found to be absolutely normal. The presence of the testis-specific protein gene
      (TSPY) was also verified by means of PCR. Necropsy findings include short vagina,
      lack of uterus and complete absence of masculine remains. Streak gonads
      concordant with previous descriptions in humans were also found.

PMID- 19864879
TI  - Radiological-pathological comparison in a case of conjoined gnatho-thoracopagus
      twins.
AB  - BACKGROUND: Conjoined twins may present an extremely wide range of complex
      congenital malformations. Because of the increasing number of attempts to
      separate them surgically, profound knowledge is needed of this abnormality
      spectrum. CASE: Ultrasonographic, radiological (X-ray, computed tomography and
      magnetic resonance imaging) and pathological findings of gnatho-thoracopagus
      conjoined twins at 18 weeks of gestation are reported, focusing on clinical
      topographic correlations. CONCLUSIONS: High-resolution imaging techniques may
      provide useful information for surgery or autopsy planning of cases with complex
      congenital malformations.

PMID- 19864880
TI  - Perinatal outcome of monochorionic twins with selective intrauterine growth
      restriction and different types of umbilical artery Doppler under expectant
      management.
AB  - OBJECTIVES: To evaluate the prognosis of monochorionic twins with selective
      intrauterine growth restriction (sIUGR), classified according to the type of
      umbilical artery Doppler, under expectant management. METHODS: The outcome of 81
      cases with isolated sIUGR was evaluated according to a classification based on
      umbilical artery (UA) Doppler diastolic flow in the IUGR twin (I: present, II:
      constantly absent/reverse, III: intermittently absent/reverse). Selective
      feticide was not considered due to legal constraints. Perinatal outcomes included
      perinatal death and neurological outcome at 6 months of age. RESULTS: From 81
      cases with the diagnosis of sIUGR, twin-twin transfusion was diagnosed in 18
      cases. This left 63 cases, of which 23 were classified as type I (36.5%), 27 as
      type II (42.9%) and 13 as type III (20.6%). Intrauterine death occurred in 4.3%
      (1), 29.6% (8) and 15.4% (2) among IUGR twins, and 4.3% (1), 22.2% (6) and 0.0%
      (0) among larger twins. Neonatal death occurred in 0.0% (0), 18.5% (5) and 0.0%
      (0) among IUGR twins, and 0.0% (0), 11.1% (3) and 23.0% (3) among larger twins.
      Neurological abnormalities at 6 months were found in 4.3% (1), 14.8% (4) and
      23.1% (3) in smaller twins and 0.0% (0), 11.1% (3) and 38.5% (5) in larger twins,
      respectively. Intact survival at 6 months was recorded in 91% (21), 37% (10) and
      61% (8) in smaller twins and 95% (22), 55% (15) and 38% (5) in larger twins,
      respectively. CONCLUSION: The outcome in monochorionic twins with sIUGR and
      abnormal umbilical artery Doppler is poor under expectant management. Normal
      Doppler seems to be associated with a good prognosis.

PMID- 19864881
TI  - Postoperative pulmonary complications after laparotomy.
AB  - BACKGROUND: The frequency of, and risks for, postoperative pulmonary
      complications (PPCs) after laparotomy are incompletely understood. The wide
      ranging incidence of PPCs in the literature reflects methodological issues
      including variable definitions of PPCs and varied patient populations.
      OBJECTIVES: We sought to elucidate the incidence of PPCs after laparotomy and
      clarify risks for their development. METHODS: We conducted a retrospective study
      of all laparotomies in adult patients on the general surgery service at our
      university-affiliated hospital in 2004. The definition of PPCs was rigorous and
      relevant in terms of key outcomes (morbidity, mortality, length of stay). We used
      a template for the review of medical records to identify PPCs and their
      consequences. RESULTS: Twenty-five PPCs (7.0%) occurred in 359 laparotomies.
      Logistic regression modeling identified the following independent predictors of
      risk: upper abdominal incisions (OR 15.3; p = 0.025), reoperation (OR 7.1; p =
      0.013), emergency surgery (OR 6.3; p = 0.001) and nasogastric tubes (OR 5.4; p =
      0.008). PPCs were associated with increased mortality (OR 6.17; p = 0.01),
      intensive care unit care (OR 13.0; p = 0.001), increased mean hospital length of
      stay (17.7 days longer; p = 0.001) and longer mean postoperative length of stay
      (15.2 days longer; p = 0.001). CONCLUSIONS: The incidence of PPCs after
      laparotomy in this study is lower than in many prior reports and reflects the
      relevant definition of PPCs used. Upper abdominal surgery carried the greatest
      risk. Reoperation was a risk not identified previously. Emergency procedures and
      the use of nasogastric tubes were confirmed as key risks. Morbidity, mortality
      and lengths of stay were significantly increased after PPCs.

PMID- 19864882
TI  - Use of multidetector row CT to evaluate the need for bronchial arterial
      embolization in hemoptysis patients.
AB  - BACKGROUND: Bronchial artery (BA) embolization (BAE) is recommended as a
      minimally invasive therapy for hemoptysis, though some patients recover after
      only conservative treatment. OBJECTIVES: The purpose of our study was to assess
      the characteristics of BAs using multidetector row computed tomography (MDCT) and
      identify BAs requiring BAE without BA angiography (BAG). METHODS: We
      retrospectively studied 41 patients and classified the visualized BAs into groups
      based on their BAE and bleeding statuses. Patients presenting with massive
      hemoptysis requiring emergency BAE were excluded. Patients presenting with
      persistent hemoptysis that was resistant to conservative treatment received BAE.
      Radiologists measured BA diameters at the ostium, bronchial bifurcation and
      pulmonary hilum, and also evaluated the degree of vascularization. RESULTS: MDCT
      enabled visualization of 102 ostia and 96 traceable BAs. Among the participating
      patients, 13 had at least one ectopic origin. We obtained a good correlation
      between BAG and MDCT diameters (r = 0.709, p < 0.001). The diameters of BAs
      responsible for bleeding and receiving BAE were apparently larger in each
      measured segment than those that were not (p < 0.05). Moreover, the diameters of
      arteries receiving BAE remained largely unchanged from the origin to the hilum
      and through the mediastinum. BAs with low MDCT scores were significantly less
      likely to required BAE than those with high scores (p = 0.004), and in multiple
      logistic regression analysis, ostium diameter and bleeding status were
      independent predictive factors for BAE. CONCLUSIONS: Evaluation of BAs on MDCT
      could be useful for identifying the anatomical characteristics of bleeding
      related BAs and determining whether BAE is indicated or whether conservative
      treatment is sufficient.

PMID- 19864883
TI  - The grandmother effect and the uniqueness of the human aging phenotype.
AB  - This issue of Gerontology includes a response by van Bodegom et al. to Herndon's
      recent article on the implications of the grandmother hypothesis for studies of
      aging and cognition. Although this hypothesis will doubtlessly continue to
      stimulate discussion, we focus here on our contention that human and non-human
      primate life histories have evolved essential differences and that these should
      be addressed in studies comparing aging in humans and chimpanzees.

PMID- 19864885
TI  - Physical activity is a determinant of circadian blood pressure variation in
      chronic kidney disease.
AB  - BACKGROUND: Circadian variation in blood pressure (BP), which is commonly blunted
      among patients with chronic kidney disease (CKD), has been associated with
      increased cardiovascular risk. The causes of this blunted circadian variation
      remain incompletely understood. METHODS: We hypothesized that physical activity
      is a determinant of circadian BP variation. Accordingly, we studied 101 patients
      with CKD (mean age 69 years, mostly men) with 24-hour ambulatory BP monitoring
      and simultaneous monitoring of physical activity on 2 occasions 4 weeks apart.
      RESULTS: Measured by wrist actigraphy, a higher level of physical activity was
      associated with lower overall mean BP. A higher level of activity also altered
      the circadian systolic BP rhythm; this alteration was characterized by both a
      higher amplitude of variation (and thus greater dipping) and restoration of
      acrophase (time at peak BP) to a less vulnerable period for cardiovascular
      events. Among the most sedentary participants, both systolic and pulse pressure
      acrophases were seen in the early hours of the morning which is also the most
      vulnerable period for cardiovascular events. CONCLUSION: Physical activity is an
      independent determinant of circadian variation in BP. We speculate that among
      patients with CKD, a sedentary lifestyle, rather than non-dipping, mediates
      increased cardiovascular risk.

PMID- 19864884
TI  - Adaptation and validation of the Kidney Disease Quality of Life-Short Form
      questionnaire in the Greek language.
AB  - AIM: The aim of this study was to examine the validity, reproducibility and
      internal consistency of a Greek translation of the Kidney Disease Quality of Life
      Short Form (KDQOL-SF) questionnaire. METHODS: The KDQOL-SF questionnaire was
      translated from English to Greek and was administered in 240 randomly selected
      patients undergoing hemodialysis in six Renal Units in Greece. The instrument's
      validity was tested by examining the association between patient's KDQOL-SF
      scores and comorbidity assessed with the Index of Coexistent Disease.
      Reproducibility was examined by readministering the questionnaire in 50 randomly
      selected patients within 1 month. Internal consistency was assessed by estimating
      Cronbach's alpha coefficient. RESULTS: Patients were divided into two groups
      according to the severity of comorbidity assessed with the Index of Coexistent
      Disease. Those with less comorbid conditions had significantly higher scores in
      most components of the KDQOL-SF questionnaire, confirming its validity. The
      correlation coefficients between the two administrations of the instrument ranged
      from 0.88 to 0.98 for each of the main components, which was above the desired
      level of 0.85. Cronbach's alpha coefficient ranged from 0.91 to 0.92 for the
      various components, values well above the minimum desired 0.70 level.
      CONCLUSIONS: The present study shows that the Greek version of the KDQOL-SF
      questionnaire has high validity, reproducibility and internal consistency.
      Production of validated translations of the KDQOL-SF questionnaire in various
      languages will help promote health-related quality of life of end-stage renal
      disease patients all over the world.

PMID- 19864886
TI  - Phosphoproteomic study of human tubular epithelial cell in response to
      transforming growth factor-beta-1-induced epithelial-to-mesenchymal transition.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta)-induced epithelial-to
      mesenchymal transition (EMT) plays an important role in renal fibrosis and
      progression of chronic kidney disease (CKD). Phosphorylation of proteins is
      essential to TGF-beta signaling. We applied isobaric tags for relative and
      absolute quantification (iTRAQ) technology to profile the phosphoproteins in
      tubular epithelial cells in response to TGF-beta-induced EMT in order to further
      study molecular events. METHODS: HK-2 cells were treated with TGF-beta1 to induce
      EMT. The cells were divided into a control group (without TGF-beta1 treatment)
      and a TGF-beta1-treated group. Phosphoproteins from two groups were extracted and
      differentially labeled with iTRAQ reagents and processed by 2D-nano-HPLC-MS/MS.
      Validating of iTRAQ analysis was performed by western blot. Bioinformatic
      analysis was performed by on-line databases. RESULTS: By iTRAQ-2D-nano-HPLC
      MS/MS, 38 differentially expressed phosphoproteins were identified which included
      19 up-regulated phosphoproteins and 19 down-regulated phosphoproteins. Western
      blot confirmed up-regulation of phosphorylated moesin and HSP90alpha.
      Bioinformatic analysis suggested that the majority of proteins were located in
      the nucleus and endoplasmic reticulum lumen. The phosphoproteins were categorized
      into 17 molecular function classifications. Nucleic acid binding protein,
      cytoskeletal protein and chaperone were the major categories of molecular
      function. A biological network was built to analyze interaction between up
      regulated proteins. CONCLUSION: We demonstrate a TGF-beta1-mediated post
      transcriptional regulation of EMT in tubular epithelial cells. Phosphorylation of
      moesin and HSP90alpha might play a role in TGF-beta-induced EMT.

PMID- 19864887
TI  - A non-human primate BAC resource to study interchromosomal segmental
      duplications.
AB  - Segmental duplications (SDs) are involved in the reshaping and evolutionary
      development of primate genome architecture. Their intrinsic property to promote
      genomic instability facilitates genome rearrangements, thereby contributing to
      karyotype diversity in primates. However, comparative analyses of SDs based on
      whole-genome shotgun assemblies of primate genomes may lead to a distorted view
      of their evolutionary dynamics as this method will incorrectly assemble or simply
      not represent these regions. Therefore high-quality sequences of chromosomally
      assigned SDs are indispensable for unraveling the amplification and dispersal
      pattern of SDs during primate evolution. Here, we use an updated version of the
      ancestral duplicon state of the non-palindromic SDs of all 4 human Y-chromosome
      euchromatin/heterochromatin transition regions to perform a survey of duplicons
      genome-wide across 7 primate species. By adjusting experimental conditions to the
      mean nucleotide sequence divergence to human we identified 11,075 BAC clones
      carrying primate orthologs or paralogs of human Y chromosome-derived duplicons.
      Preliminary results indicate lineage-specific amplification of duplicons in
      prosimians and gibbons. This BAC-based framework represents the first complete
      set of a defined number of duplicons over 60 million years of primate evolution.
      Comparative sequence analysis of this genetic resource can contribute to our
      deeper understanding of the impact of segmental duplications on primate genome
      evolution.

PMID- 19864888
TI  - New metacentric population of the house mouse (Mus musculus domesticus) found in
      Valchiavenna, Northern Italy.
AB  - Although the standard karyotype of the western house mouse (Mus musculus
      domesticus) consists entirely of telocentric chromosomes, there are over 100
      populations across western Europe and North Africa characterized by different
      sets of metacentrics formed by Robertsonian fusions and whole-arm reciprocal
      translocations. Here we report the discovery of a new metacentric population from
      Valchiavenna, northern Italy, that we have named the 'Lower Valchiavenna
      population' (abbreviated as ILVC). This metacentric population is found in
      villages and on farms over a 10-kilometer stretch comprising the southern half of
      Valchiavenna. ILVC is characterized by the metacentrics 1.18, 2.4, 3.8, 5.15,
      6.7, 9.14, 10.12, 11.13 and 16.17, and appears to be closely related to the
      Chiasso population (CHCH), which possesses the same set of metacentrics except
      1.18. We discuss the evolutionary origin of ILVC in relation to human occupation
      of the region. We also suggest that the geographical position of ILVC between 2
      other metacentric populations with entirely different sets of metacentrics
      (Chiavenna, ICHI, and lower Valtellina, ILVA) may provide 2 additional
      chromosomal hybrid zones for the study of speciation.

PMID- 19864889
TI  - The 450-band resolution G- and R-banded standard karyotype of the donkey (Equus
      asinus, 2n = 62).
AB  - Donkey chromosomes were earlier characterized separately by C-, G- and R-banding
      techniques. However, direct comparisons between G- and R-banding patterns have
      still not been carried out in this species. The present study reports this
      comparison at the 450-band level by using replication G- and R-banding patterns.
      Two sets of synchronized lymphocyte cultures were set up to obtain early (GBA+CBA
      banding) and late (RBA-banding) BrdU incorporation. Slides were stained with
      acridine orange and observed under a fluorescence microscope. Reverse GBA+CBA-
      and RBA-banded karyotypes at the 450-band level were constructed. To verify G-
      and R-banding patterns in some acrocentric chromosomes, sequential GBA+CBA/Ag
      NORs and RBA/Ag-NORs were also performed. The results of CBA-banding patterns
      obtained in 12 animals from 2 breeds showed a pronounced polymorphism of
      heterochromatin, especially in EAS1q-prox. Ideogrammatic representations of G-
      and R-banded karyotypes were constructed using only one common G- and R-banding
      nomenclature. In the present study both G- and R-banding patterns and relative
      ideograms are presented as standard karyotype for this species at the 450-band
      level.

PMID- 19864890
TI  - Characterisation of a GC-rich telomeric satellite DNA in Eumeces schneideri
      Daudin (Reptilia, Scincidae).
AB  - A hitherto undescribed satellite DNA family (AvaII satDNA) has been isolated and
      characterised in Eumeces schneideri, a squamate reptile belonging to the family
      Scincidae. AvaII satDNA is characterised by a monomer length of 208 bp, a GC
      content of 59% and exhibits a certain degree of CpG methylation. FISH experiments
      with AvaII satDNA probe produced bright signals (i) at the end of the short arms
      of all subtelocentric chromosomes except for pair 14, in which the signal was at
      the end of the long arms, (ii) at the ends of both arms of the small metacentric
      chromosomes 12, and (iii) in a terminal position on the acrocentric chromosomes
      11 and 13. AvaII satDNA repeats were not found in the metacentric pair 3, whereas
      only a weak interstitial signal occurred in the metacentric pairs 1 and 2. C
      banding showed that this satellite represents most of the constitutive
      heterochromatin in the genome of this skink, and chromomycin A(3) staining
      produced a clear signal overlapping with the satellite, except for NOR-associated
      heterochromatin. In addition, quantitative dot blot analysis showed that these
      repetitive sequences constitute about 3% of the genomic DNA of this lizard. AvaII
      satDNA sequence analysis revealed the occurrence of short guanine residue
      stretches for which a function in structural stability of these sequences and a
      role in recombination with telomeric sequences can be hypothesised. Fibre FISH
      experiments showed that on some chromatin fibres telomeric sequences and AvaII
      satellite DNA repeats are intermingled or overlapping.

PMID- 19864891
TI  - Genetic mapping of the ornithine decarboxylase (odc) gene complex in rainbow
      trout (Oncorhynchus mykiss).
AB  - Ornithine decarboxylase (odc) and its associated gene complex, including
      antizymes of ODC and inhibitors of the antizymes, play a key role in regulating
      the overall polyamine levels (i.e., putrescine) in cells. Polyamine production
      levels are intricately coupled to mitotic and cellular turnover rates. Hence,
      these genes may be important candidates of growth regulation in vertebrates, if
      their chromosomal locations coincide with known quantitative trait locus (QTL)
      regions influencing growth traits. Here we report the genetic mapping of multiple
      duplicated forms of genes within this complex to previously known life-history
      and growth QTL regions in rainbow trout (Oncorhynchus mykiss). Specifically,
      duplicated copies of the 2 antizyme genes map to Om-8/9/24, while antizyme
      inhibitor and odc duplicates map to Om-27/31 and Om-14/25, respectively. All sets
      of paralogous mapping locations correspond to ancestrally duplicated synteny
      regions within the genome of rainbow trout (i.e., ancestral A, B, GH/I and M
      linkage groups).

PMID- 19864892
TI  - Microdissection and chromosome painting of X and B chromosomes in the grasshopper
      Eyprepocnemis plorans.
AB  - The relative location of 2 repetitive DNAs, i.e. ribosomal (rDNA) and a tandemly
      repeated satellite DNA (satDNA), with respect to the centromere, suggested that B
      chromosomes in the grasshopper Eyprepocnemis plorans derived intraspecifically
      from the X chromosome. To test this hypothesis, we microdissected X and B
      chromosomes and amplified the obtained DNA by 2 different procedures, the
      conventional DOP-PCR method and the single-cell whole-genome amplification
      GenomePlex method. We then generated DNA probes to perform chromosome painting.
      Our results have confirmed that X and B chromosomes share many DNA sequences
      between them and with most of the autosomes, especially at locations where the
      satDNA and rDNA reside, in consistency with previous information. This supports
      the hypothesis of an intraspecific origin of B chromosomes in E. plorans.
      Nevertheless, the present results did not help to clarify whether Bs were derived
      from the X chromosome or else from 1 or more autosomes.

PMID- 19864893
TI  - Sex chromosome evolution in cotton stainers of the genus Dysdercus (Heteroptera:
      Pyrrhocoridae).
AB  - The neo-X and neo-Y sex chromosomes of Dysdercus albofasciatus represent a unique
      model for the study of early stages of sex chromosome evolution since they
      retained the ability to pair and recombine, in contrast to sex chromosomes in
      most Heteroptera. Here we examined structure, molecular differentiation, and
      meiotic behaviour of the D. albofasciatus neo-sex chromosomes. Two related
      species with the ancestral X0 system, D. chaquensis and D. ruficollis, were used
      for a comparison. In D. albofasciatus, 2 nucleolar organizer regions (NORs) were
      identified on the neo-X chromosome using fluorescence in situ hybridization
      (FISH) with an rDNA probe, whereas a single NOR was found on an autosomal pair in
      the other 2 species. Genomic in situ hybridization (GISH) differentiated a part
      of the original X in the neo-X chromosome but not the neo-Y chromosome. The same
      segment of the neo-X chromosome was identified by Zoo-FISH with a chromosome
      painting probe derived from the X chromosome of D. ruficollis, indicating that
      this part is conserved between the species. Immunostaining against the cohesin
      subunit SMC3 revealed that only terminal regions of the D. albofasciatus neo-Xneo
      Y bivalent pair and form a synaptonemal complex, which is in keeping with the
      occurrence of terminal chiasmata, whereas the interstitial region forms a large
      loop indicating the absence of homology. These results support the hypothesis
      that the neo-X chromosome evolved by insertion of the original X chromosome into
      1 NOR-bearing autosome in an ancestor carrying the X0 system. As a consequence,
      the homologue of this NOR-autosome became the neo-Y chromosome. A subsequent
      inversion followed by transposition of the NOR located on the neo-Y onto the neo
      X chromosome resulted in the present neo-sex chromosome system in D.
      albofasciatus.

PMID- 19864894
TI  - Superior: a novel repetitive DNA element dispersed in the rye genome.
AB  - A new class of rye-specific repetitive DNA elements designated Superior has been
      identified. The rye genome library was constructed by cleavage with EcoO109I, the
      recognition sites of which consisted of 5'-PuGGNCCPy-3' multi-sequences and were
      present with high frequency in the rye repetitive families. A novel 495-bp
      segment enriched in the rye genome was successfully identified. Southern blot
      hybridization and fluorescence in situ hybridization using the repetitive element
      showed a dispersed array through all 7 chromosomes of rye. The repetitive DNA
      element did not share identity with known class I or class II transposable
      elements or known repetitive elements. Only several DNA segments in BACs and ESTs
      of barley showed partial similarity to the repetitive DNA element in all DNA
      databases of living species. The new class of dispersed repetitive elements was
      designated Superior. The entire structure of Superior was determined by using a
      rye genomic library of lambda FIXII screened by the 495-bp probe. The Superior
      family consisted of 1,292-bp, 1,324-bp, and 1,432-bp elements in which the 5'
      regions had been destroyed, indicating the presence of considerable structural
      diversity. Superior might be a useful tool for studying genomic organization and
      differentiation.

PMID- 19864895
TI  - Localization of Rad50, a single-copy gene, on group 5 chromosomes of wheat, using
      a FISH protocol employing tyramide for signal amplification (Tyr-FISH).
AB  - An indirect tyramide signal amplification FISH technique (Tyr-FISH) was adapted
      to detect single-copy genes in plants. In this study, Rad50 loci (responsible for
      a protein involved in the repair of breaks in double-stranded DNA) were localized
      on the chromosomes of homologous group 5 in common wheat (Triticum aestivum).
      Three loci, Rad50A, Rad50B and Rad50D, none of which have been previously mapped
      using any kind of molecular approach, were localized at similar positions on the
      short arm of chromosomes 5A, 5B and 5D, respectively. The loci are all proximal
      to 5S ribosomal gene clusters. The sensitivity and efficiency of the Tyr-FISH
      technique was tested using 5 differently sized fragments of the gene Rad50D as
      probes in FISH involving the chromosomes of the diploid wheat Triticum tauschii
      (the D-genome donor species of the hexaploid wheats). The procedure, which
      provided specific signal amplification with low level background, detected target
      DNA sequences as small as 2 kb with a frequency of 37.5%.

PMID- 19864896
TI  - Centromeric alpha-satellite DNA break in reciprocal translocations.
AB  - In the process of selecting fluorescence in situ hybridization probes to be used
      for preimplantation genetic diagnosis in couples with balanced reciprocal
      translocations, we found 2 individuals with unexpected breaks in the centromeric
      alpha-satellite DNA. Subsequently, centromere breaks were specifically sought in
      reciprocal translocations in which 1 or both breakpoints appeared cytogenetically
      near the centromere. In a total of 11 individuals studied, we found 8 centromere
      breaks in 6 individuals; in 2 individuals, the alpha-satellite DNA of both
      chromosomes involved in the translocation split into 2 arrays. These findings
      suggest that breaks in alpha-satellite DNA are not rare events. Together with
      those previously reported in the literature, alpha-satellite DNA breaks of at
      least chromosomes X, 1, 4, 5, 10, 11, 16, 17, 18, and 19 have now been
      documented. The breaks are familial in 2 of the 6 cases in our study, indicating
      the derivative chromosomes are both mitotically and meiotically stable. These
      derivative chromosomes that are either cytogenetically dicentric or molecular
      cytogenetically dicentric, or have altered amounts of alpha-satellite DNA may
      prove to be valuable in studying centromere dynamics and biology.

PMID- 19864897
TI  - Characterization of a 5.8-Mb interstitial deletion of chromosome 3p in a girl
      with 46,XX,inv(7)dn karyotype and phenotypic abnormalities.
AB  - Interstitial deletions of the short arm of chromosome 3 are rare, and a specific
      clinical phenotype has not been defined. We report the first isolated cryptic
      proximal interstitial 3p deletion, del(3)(p12.3p13), assessed by array-based
      comparative genomic hybridization in a girl with an inversion of chromosome 7,
      whose phenotype includes neurodevelopmental delay, growth retardation, dysmorphic
      facial features, hypophysis hypoplasia, gastroesophageal reflux, clinodactyly,
      preauricular appendix, and myopia. Her features are similar to those observed in
      the previously reported cases of proximal 3p deletions overlapping with our
      imbalance, indicating that her clinical manifestations are likely to be due to
      the deletion. As our patient's imbalance is the first non-cytogenetically visible
      proximal interstitial 3p deletion uncomplicated by other imbalances, its
      characterization has allowed us to narrow the minimal deletion interval
      associated with growth retardation and neurodevelopmental delay to the 3p12.3-p13
      region. Among the genes found in this region, ROBO1, ROBO2, PDZRN3 and CNTN3
      might play a role in the neurodevelopmental delay of the patient. This study
      provides additional evidence that cryptic imbalances anywhere along the genome
      can be found in patients with phenotypic abnormalities and a balanced chromosome
      rearrangement.

PMID- 19864898
TI  - The number one cause for sudden cardiac death in the young unravels.

PMID- 19864899
TI  - Cardiomyopathy: a systematic review of disease-causing mutations in myosin heavy
      chain 7 and their phenotypic manifestations.
AB  - BACKGROUND: Mutations in myosin heavy chain 7 (MYH7) commonly cause
      cardiomyopathy. However, the relationship between mutation location,
      cardiomyopathy type, change in amino acid composition and disease severity is
      poorly understood. This systematic review aims to provide, on a large scale,
      important insights into the role mutations in MYH7 play in cardiomyopathy.
      METHODS: The literature was searched from 1966 to March 2009. The mutation
      location, type of mutation and disease type and severity were documented. When
      the severity of disease was known, the change in charge and hydropathy of the
      mutation was determined. Where appropriate, either a chi(2) test was used or a
      relative risk ratio was calculated in order to evaluate the data. RESULTS: The
      data presented in this study demonstrate that there are proportionately more
      mutations in the head and neck regions of this gene than in the tail.
      Importantly, mutations in the head of the gene, those that cause large changes in
      the hydropathy of the amino acid and non-conservative mutations are more likely
      to lead to a severe phenotype. CONCLUSIONS: This study suggests that mutation
      location in the MYH7 gene and changes in amino acid composition can have a
      negative impact on the disease outcome in individuals with cardiomyopathy.

PMID- 19864900
TI  - Risk factor conundrum.

PMID- 19864901
TI  - Circulating adiponectin: associations with risk factors and the Reynolds risk
      score in women without prior major cardiovascular events.
AB  - OBJECTIVE: Adiponectin may play an important role in the interplay between
      metabolic changes and cardiovascular risks. Our aim was to establish if plasma
      adiponectin can be used to detect the metabolic syndrome (MetS) in women without
      a history of major cardiovascular events and to evaluate its correlation with the
      global cardiovascular risk expressed by the Reynolds risk score (RRS). METHODS:
      148 consecutive women without a history of cardiovascular events with or without
      MetS have been investigated. Clinical risks factors as well as plasma levels of
      lipids, fasting glucose and adiponectin were determined. RESULTS: As expected,
      circulating adiponectin was lower in women with MetS: 26.8 +/- 20.4 versus 44.3
      +/- 26.7 microg/ml (p < 0.001) and inversely related to the number of MetS
      features (r = -0.33, p < 0.001). The latter was further associated with the total
      cardiovascular risk calculated using RRS (r = 0.49, p < 0.001). However, there
      was no relationship between circulating adiponectin and this score (r = -0.14, p
      = NS). CONCLUSIONS: Plasma adiponectin levels are significantly lower in women
      with MetS, but as a stand-alone tool plasma adiponectin may be of little value in
      the diagnosis MetS. Circulating adiponectin levels are not associated with the
      global cardiovascular risk calculated using RRS.

PMID- 19864902
TI  - Cardiomyopathy and kidney disease in a patient with maternally inherited diabetes
      and deafness caused by the 3243A>G mutation of mitochondrial DNA.
AB  - Cardiomyopathy is a manifestation of mitochondrial cytopathies, but rarely
      constitutes the dominant feature, especially in adults. We report the case of a
      59-year-old male with a personal and maternal history of diabetes and deafness,
      who presented with cardiomyopathy and kidney disease. We diagnosed the patient as
      having a mitochondrial cytopathy resulting from the 3243A>G mutation on the
      tRNA(Leu(UUR)) gene in the mitochondrial DNA. The family history, broad spectrum
      of clinical manifestations and fluctuant clinical course provided clues to the
      diagnosis. We discuss the possible mechanisms underlying the phenotypic
      variability and fluctuant clinical course of mitochondrial disorders and the
      potential usefulness of coenzyme Q10 and L-carnitine in 3243A>G mutation
      patients.

PMID- 19864903
TI  - Efficacy of an experimental tin-F-containing solution in erosive tissue loss in
      enamel and dentine in situ.
AB  - The aim of this study was to evaluate the effects of an experimental tin
      containing fluoride solution on erosive tissue loss in human enamel and dentine
      using a cyclic de- and remineralization model in situ. The study was a three-cell
      (7 days each) crossover design involving 20 healthy volunteers. Samples were
      mounted on buccal shields of mandibular mouth appliances and worn for 24 h,
      except during meals and oral hygiene. Samples were demineralized extraorally with
      0.05 M citric acid (pH 2.3) for 6 x 5 min per day. Fluoride treatment was
      performed intraorally once per day for 30 s after the first demineralization.
      Three solutions were used: placebo (negative control); NaF solution (positive
      control, 1,000 mg/kg F, pH 4.5), and an experimental solution (1,900 mg/kg Sn as
      SnCl(2), 500 mg/kg F as NaF, 500 mg/kg F as amine fluoride, pH 4.5). Tissue loss
      was determined profilometrically. In enamel, tissue loss was 33.6 +/- 15.4 microm
      in the negative control group, 24.2 +/- 9.2 microm (p < or = 0.05) in the
      positive control group and 9.2 +/- 3.4 microm (p < or = 0.001) in the
      experimental solution group. The respective values for dentine were 47.8 +/- 15.5
      microm in the negative control group, 34.1 +/- 9.3 microm (p < or = 0.001) in the
      positive control group and 23.9 +/- 6.4 microm (p < or = 0.001) in the
      experimental solution group. The tin-containing solution was very effective in
      inhibiting erosive mineral in enamel in situ, even under severe conditions and
      with short application times, but was less effective in dentine.

PMID- 19864904
TI  - Comparison of calcium analysis, longitudinal microradiography and profilometry
      for the quantitative assessment of erosion in dentine.
AB  - Erosion of dentine causes mineral dissolution, while the organic compounds remain
      at the surface. Therefore, a determination of tissue loss is complicated.
      Established quantitative methods for the evaluation of enamel have also been used
      for dentine, but the suitability of these techniques in this field has not been
      systematically determined. Therefore, this study aimed to compare longitudinal
      microradiography (LMR), contacting (cPM) and non-contacting profilometry (ncPM),
      and analysis of dissolved calcium (Ca analysis) in the erosion solution. Results
      are discussed in the light of the histology of dentine erosion. Erosion was
      performed with 0.05 M citric acid (pH 2.5) for 30, 60, 90 or 120 min, and erosive
      loss was determined by each method. LMR, cPM and ncPM were performed before and
      after collagenase digestion of the demineralised organic surface layer, with an
      emphasis on moisture control. Scanning electron microscopy was performed on
      randomly selected specimens. All measurements were converted into micrometres.
      Profilometry was not suitable to adequately quantify mineral loss prior to
      collagenase digestion. After 120 min of erosion, values of 5.4 +/- 1.9 microm
      (ncPM) and 27.8 +/- 4.6 microm (cPM) were determined. Ca analysis revealed a
      mineral loss of 55.4 +/- 11.5 microm. The values for profilometry after matrix
      digestion were 43.0 +/- 5.5 microm (ncPM) and 46.9 +/- 6.2 (cPM). Relative and
      proportional biases were detected for all method comparisons. The mineral loss
      values were below the detection limit for LMR. The study revealed gross
      differences between methods, particularly when demineralised organic surface
      tissue was present. These results indicate that the choice of method is critical
      and depends on the parameter under study.

PMID- 19864905
TI  - Study of the efficacy of toothpaste containing casein phosphopeptide in the
      prevention of dental caries: a randomized controlled trial in 12- to 15-year-old
      high caries risk children in Bangalore, India.
AB  - Casein phosphopeptide (CPP) has the potential to be added to mouth rinses, gels,
      toothpastes, chewing gums and confectioneries. Until now CPP has been studied in
      vitro, in situ and in animals, but clinical trials are lacking. This study was
      conducted to evaluate the efficacy of CPP-containing toothpaste in preventing
      dental caries in schoolchildren. The study was conducted among 150 schoolchildren
      randomly divided into three groups, each using one of three types of toothpastes:
      (a) containing 2% w/w CPP; (b) containing 1,190 mg/kg fluoride as 0.76% sodium
      monofluorophosphate (SMFP); (c) placebo toothpaste without CPP or fluoride.
      Students brushed with the given toothpastes for 24 months. Oral hygiene and
      caries experience were assessed at baseline, 12 and 24 months. The increments in
      caries lesions were calculated and analyzed to assess the caries-preventive
      effect. A significant reduction in caries increment was observed among students
      using CPP toothpaste or SMFP toothpaste, compared with the group using the
      placebo toothpaste. The reduction in caries increment was not significantly
      different between the CPP and SMFP groups. Oral Hygiene Index score increased
      from the 12-month to the 24-month examination. It is concluded that CPP can be
      effectively incorporated into calcium carbonate-based toothpaste and that
      toothpaste containing CPP is effective in preventing caries. Toothpaste
      containing 2% CPP seemed to have an efficacy similar to paste containing 1,190
      mg/kg SMFP in the prevention of caries.

PMID- 19864906
TI  - What difference does using bitewing radiographs make to epidemiological estimates
      of dental caries prevalence and severity in a young adolescent population with
      high caries experience?
AB  - The study aimed to determine the relative contributions of bitewing radiography
      and clinical examination to caries estimates for a New Zealand child population
      with high caries experience. An epidemiological survey was conducted of 171 12-
      and 13-year-old children attending schools in five communities. Examinations were
      conducted in dental clinics. Bitewing radiographs were taken at the time of the
      clinical examination. These were developed and read later, and the data from
      those were used at the analysis stage to adjust the caries diagnosis for the
      mesial, occlusal and distal surfaces of the posterior teeth. For almost all
      parameters, the use of radiographs resulted in higher estimates, although at the
      whole-mouth prevalence level the difference was not great. The percent difference
      between the estimates ranged from -0.1 to 166.7%. There were moderate differences
      between the clinical-only and radiographically adjusted whole-mouth estimates for
      mean DMFT, DT, DMFS and DS, but only a minor difference in caries prevalence.
      With the mesial and distal surfaces only, the prevalence and severity estimates
      were significantly greater, with a one-surface difference (on average) in mean DS
      being the largest difference observed, at 166.7%. The diagnostic discrepancy was
      much greater for approximal than occlusal surfaces. These findings support but
      also build upon earlier findings and again underline the need for bitewing
      radiographs to be a routine part of oral epidemiological surveys wherever
      logistics and funding permit.

PMID- 19864907
TI  - Molecular status of plasma fibronectin as an additional biomarker for assessment
      of Alzheimer's dementia risk.
AB  - BACKGROUND: Aberrant angiogenesis and senescence of the cerebrovascular system
      could initiate neurovascular events leading to neurovascular disorders.
      Fibronectin (FN) exerts a strong angiogenic influence on endothelial cells in the
      central nervous system. METHODS: In the present study the expression of the
      plasma fibronectin molecular forms in an Alzheimer patient group, compared with
      vascular dementia and age-matched control groups was analyzed by immunoblotting.
      RESULTS: FN in the plasma of the elderly individuals with and without dementia
      exists as a mixture of heterogeneous molecules with increasing molecular masses.
      Apart from the wide approximately 240-kDa and approximately 220-kDa FN bands,
      normally present in plasma, the high molecular FN forms having approximately 280
      kDa and approximately 320 kDa appeared in the plasma of the Alzheimer dementia
      group more frequently and at the higher amounts than in the vascular dementia and
      age-matched nondemented groups. CONCLUSIONS: The plasma FN molecular status seems
      to be a molecular additional biomarker for assessment of dementia risk.

PMID- 19864908
TI  - Validation of Addenbrooke's cognitive examination (ACE) in a Persian-speaking
      population.
AB  - Use of reliable screening and diagnostic tests for assessment of cognitive
      abilities in neurological patients is rapidly increasing in clinical practice.
      This is due to the increase in the prevalence of dementias and the raised
      awareness of cognitive impairment in neurological disorders. Two well-known
      bedside screening tests for dementias among the English-speaking population are
      the Mini Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination
      (ACE). However, such tests have not been developed for the Persian-speaking
      population, which is estimated at 120 million worldwide. In this study we
      developed the Persian ACE and MMSE, adopted from the English version. We also
      assessed the sensitivity and specificity of these tests in the identification of
      Alzheimer's disease (AD) and mild cognitive impairment (MCI). We found that the
      Persian ACE at a cutoff point of 84, has a sensitivity of 93% and a specificity
      of 91% in discriminating MCI from a normal population; at 78, the test has a
      sensitivity of 73% and a specificity of 93% in differentiating MCI from AD, and
      at a similar cutoff point has a sensitivity of 100% and specificity of 96% in
      discriminating AD from a normal population. We conclude that the Persian ACE is a
      valuable tool in clinical practice in the Persian-speaking population.

PMID- 19864909
TI  - Subcortical vascular dementia biomarker pattern in mild cognitive impairment.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is an etiologically unclear disorder.
      Cerebrospinal fluid (CSF) biomarkers are potentially useful for the
      differentiation between various MCI etiologies. AIM: The aim of the study was to
      assess whether baseline CSF hyperphosphorylated tau (P-tau), total tau (T-tau),
      amyloid beta 1-42 (Abeta(42)) and neurofilament light (NF-L) in patients with MCI
      could predict subcortical vascular dementia (SVD) and Alzheimer's disease (AD) at
      follow-up. METHODS: Biomarker levels were assessed by Luminex xMAP technology and
      ELISA. RESULTS: Increased baseline concentrations of NF-L significantly separated
      MCI-SVD from stable MCI. The MCI-SVD patients were inseparable from stable MCI
      but separable from patients developing AD (MCI-AD) on the basis of Abeta(42,) T
      tau and P-tau(181) levels. CONCLUSION: A combination of the biomarkers Abeta(42),
      T-tau, P-tau(181) and NF-L has the potential to improve the clinical separation
      of MCI-SVD patients from stable MCI and MCI-AD patients.

PMID- 19864910
TI  - Liver regeneration: focus on cell types and topographic differences.
AB  - BACKGROUND/AIMS: The liver has a remarkable capacity to regenerate after injury
      or resection. The aim of the current review is to outline the morphological
      changes at the cellular level and the intralobular differences during the
      regenerative response after partial hepatectomy. METHODS: Relevant studies were
      reviewed using the Medline database. RESULTS: At 24 h after partial hepatectomy,
      many alterations between the periportal and pericentral regions of the hepatic
      lobule occur, which coincide with the peak of hepatocellular proliferation in the
      periportal areas. Questions unanswered involve the precise role of Kupffer cells
      and whether the regenerative process is characterized by a net increase in the
      number of lobules or by an increase in the size of the existing lobules.
      CONCLUSIONS: Liver regeneration has been studied for many years, but further
      research is essential, since in-depth knowledge of the mechanisms that govern the
      regenerative process may expand the treatment options in patients with hepatic
      disease.

PMID- 19864911
TI  - Who was standing at the cradle of phoniatrics? To celebrate the 90th anniversary
      of the name of our medical specialty.
AB  - Since the very beginnings of medicine, physicians have been concerned with the
      study of normal and the therapy of disturbed verbal communication. However, no
      professional name for their specific activities has been handed down. The ancient
      Athenian phonascoi and Roman phonasci were voice trainers and not physicians
      although they also advised the performers on dietetic and behavioral measures.
      The British throat specialist Sir Morell Mackenzie was the first physician who
      called himself - in the eighties of the 19th century - phoniatros. Yet, his
      pioneering work found no echo and was reported only eight decades later. Hermann
      Gutzmann Sr. is credited as the founder of phoniatrics. In fact, in 1905 he laid
      the foundation for this specialty but he called it medical voice and speech
      pathology (Sprachheilkunde). The present-day name of phoniatrics was first used -
      independently of Mackenzie's proposal - by Miloslav Seeman and Hugo Stern, and it
      was the latter of the two who introduced it in 1919 to the public. After the
      formation of the International Association of Logopedics and Phoniatrics (IALP)
      by Emil Froschels in 1924, phoniatrics has been accepted worldwide as the
      official name of medical communicology.

PMID- 19864912
TI  - Electroglottogram-based estimation of vocal economy: 'quasi-output-cost ratio'.
AB  - Impact stress (IS) has been regarded as the main loading factor in voice
      production. To quantify the cost of voice production, an output-cost ratio (OCR)
      was proposed, which concerns acoustic output (pressure P) in relation to IS: OCR
      = 20 log P(sup)/P(0) - 20 log IS/IS(0) [1,2]. IS is difficult to measure directly
      in humans. However, it has been found to correlate with closed quotient (CQ,
      closed time/period length) measured by electroglottogram (CQ(EGG)) [3]. The
      present study proposes a noninvasive estimate of OCR, the quasi-output-cost ratio
      (QOCR): (sound pressure level (SPL)/CQ(EGG)) x (period length (T)/T(0)). T(0) is
      set at 0.005 for females and 0.01 for males, corresponding to the respective
      period lengths of the mean F(0) in female and male speech (i.e. 200 and 100 Hz).
      QOCR was tested for 62 healthy females (23 teachers, 18 university students with
      voice training and 21 without). The teachers had a higher QOCR than the students
      in loud speech, but QOCR did not correlate with symptoms of vocal fatigue after a
      vocal loading test. QOCR seems to be a promising tool to quantify vocal loading
      but naturally not vocal loadedness.

PMID- 19864913
TI  - Auditory processing in children with specific language impairments: are there
      deficits in frequency discrimination, temporal auditory processing or general
      auditory processing?
AB  - BACKGROUND/AIMS: Specific language impairment (SLI) is believed to be associated
      with nonverbal auditory (NVA) deficits. It remains unclear, however, whether
      children with SLI show deficits in auditory time processing, time processing in
      general, frequency discrimination (FD), or NVA processing in general. PATIENTS
      AND METHODS: Twenty-seven children (aged 8-11) with SLI and 27 control children
      (CG), matched for age and gender, were retrospectively compared with regard to
      their performance on five NVA skills in terms of just noticeable differences
      (JND) and time order judgments (TOJ). JND was used for FD, intensity
      discrimination, and gap detection, while TOJ was used for FD and clicks. RESULTS:
      Children with SLI performed significantly worse than the CG only on the FD tasks
      (JND and TOJ). The other nonverbal tasks showed no significant intergroup
      differences. Additionally, moderate associations were found between the FD tasks
      and phonological skills, as well as between FD tasks and language scores.
      CONCLUSION: Children with SLI appear to have restricted FD skills compared to
      controls, but there was no evidence for a common NVA deficit or reduced temporal
      auditory abilities.

PMID- 19864914
TI  - Statistical models of F2 slope in relation to severity of dysarthria.
AB  - OBJECTIVE: This study investigated the distribution of second-formant (F2) slopes
      in a relatively large number of speakers with dysarthria associated with two
      different underlying diseases. PATIENTS AND METHODS: Forty speakers with
      dysarthria (20 with Parkinson's disease, PD; 20 with stroke) and 5 control
      speakers without a history of neurological disease were asked to repeat six words
      (coat, hail, sigh, shoot, row and wax) 10 times. Acoustic analysis was performed
      to derive F2 slope, and speech intelligibility data were collected using a direct
      magnitude estimate technique to examine its relationship to F2 slope. RESULTS:
      Statistical analysis revealed that both clinical groups showed significantly
      reduced F2 slopes compared to healthy speakers for all words but row. No group
      difference was found between speakers with PD and stroke; however, different
      words showed varying sensitivity to the speech motor control problems. The F2
      slopes of only two words, shoot and wax, were significantly correlated with
      scaled speech intelligibility. CONCLUSION: The findings support the idea that
      distributional characteristics of acoustic variables, such as F2 slope, could be
      used to develop a quantitative metric of severity of speech motor control
      deficits in dysarthria, when the materials are appropriately selected and
      additional distributional characteristics are studied.

PMID- 19864915
TI  - School-aged children's production of /s/ and /r/ consonant clusters.
AB  - OBJECTIVE: To describe the acquisition of /s/ and /r/ word-initial consonant
      clusters across 2 elicitation modalities. PATIENTS AND METHODS: Seventy-four
      typically developing children aged 5-12 years produced 2- and 3-element /s/ and
      /r/ consonant clusters in word-initial position. Stimuli were presented
      pictorially and as written words in separate trials. RESULTS: Overall, 94.5% of
      the consonant clusters were produced correctly. Two-element /r/ clusters were
      94.0% correct, 2-element /s/ clusters were 96.8% correct, and 3-element clusters
      were 92.0% correct. The age of acquisition was typically younger than established
      by previous researchers. The characteristic non-adult production of /s/ consonant
      clusters was the substitution of /s/ with interdental or lateral phonemes, and of
      /r/ consonant clusters the substitution of /r/ with [w]. The last consonant
      clusters to be mastered were: /thetar/ (thr), /str/, /spr/ and /skr/. There were
      no significant differences in error rates across the modalities; although younger
      children required significantly more prompting when naming written words.
      CONCLUSION: Primary-school-aged children characteristically produced /s/ and /r/
      consonant clusters correctly. The accuracy of production was not influenced by
      the elicitation modality. Elicitation using pictures compared with written words
      was more efficient for 5- to 8-year-olds. Both elicitation modes were equally
      efficient for 9- to 12-year-olds.

PMID- 19864916
TI  - Objective acoustic analysis of pathological voices from patients with vocal
      nodules and polyps.
AB  - OBJECTIVE: We aim to examine the abilities of objective acoustic analysis methods
      (nonlinear dynamic and traditional perturbation measures) to describe voices from
      individuals with vocal nodules and polyps. SUBJECTS AND METHODS: Sustained vowel
      recordings from normal subjects, patients with vocal nodules, and patients with
      vocal polyps were analyzed. Perturbation measures of jitter and shimmer were
      obtained with the Multi-Dimensional Voice Program (MDVP) and CSpeech. Signal-to
      noise ratio was calculated using CSpeech. Nonlinear dynamic measures of phase
      space reconstruction and correlation dimension were also applied to analyze the
      voices. RESULTS: A significant difference between normal and polyp groups was
      found in jitter and shimmer obtained from MDVP, as well as in jitter and signal
      to-noise ratio from CSpeech. However, no parameters significantly differentiated
      between normal and nodule groups. Shimmer from CSpeech did not reveal any
      significant differences among any of the groups. Correlation dimension values for
      the nodule and polyp groups were significantly higher than the normal group.
      CONCLUSION: Nonlinear dynamic analysis has great potential value for the
      characterization of voice from patients with vocal nodules and polyps. The
      combination of traditional perturbation and nonlinear dynamic measures may
      improve our ability to provide objective clinical analysis of voices with vocal
      mass lesions.

PMID- 19864917
TI  - Condensed tannin intake in spiny-forest-dwelling Lemur catta at Berenty reserve,
      Madagascar, during reproductive periods.
AB  - Primates vary in their choice or avoidance of plant foods high in condensed
      tannins (CT). Our study focused on CT intake in two groups of Lemur catta
      residing in spiny forest habitat during two reproductive periods. We examined
      whether L. catta in this habitat avoided plant foods high in CT, and whether
      reproductive females ingested lower concentrations of CT compared with males,
      since CT consumption compromises protein absorption. Feeding data and plant food
      samples were collected during reproductive periods in 2006 (early/mid-lactation)
      and 2007 (early gestation). Food samples were assayed for CT content, and average
      CT intake was determined for all focal animals. No significant difference was
      found in CT content of the most commonly consumed foods compared with other foods
      in each season or between seasons. No sex differences occurred in CT consumption
      in either reproductive period. These L. catta did not avoid plant foods high in
      CT, and three strategies - ingesting small amounts of CT regularly, high amounts
      only over short periods, and geophagy - may assist these lemurs in coping with CT
      content in their highly seasonal diet. L. catta may also be somewhat
      physiologically adapted to cope with CT concentrations in their plant foods.

PMID- 19864918
TI  - Factors affecting the distribution of copulatory plugs in rhesus monkeys (Macaca
      mulatta) on Cayo Santiago.
AB  - Although the proximate mechanisms behind the formation of copulatory plugs are
      well understood, their distribution and function among primates remain largely
      unstudied. During a study of female rhesus macaque (Macaca mulatta) mating
      behaviour on Cayo Santiago, we examined the pattern of the distribution of
      visible copulatory plugs among females and their potential relationship to female
      reproductive traits and sexual skin colouration. Our results indicate that non
      pregnant females were observed more frequently with visible copulatory plugs than
      were pregnant females. Female parity status, age and rank were unrelated to
      copulatory plug observation. Genital colouration components were higher among
      females observed with copulatory plugs. We suggest that although copulatory plugs
      are generally thought of in terms of male physiology, plug observation may also
      be affected by female reproductive status.

PMID- 19864919
TI  - Patterns of water use in primates.
AB  - Aquatic resources are used extensively by many human populations but their role
      in the ecology of other primate species has been understudied. At least 10% of
      extant primates interact with aquatic environments, and a more complete
      understanding of these interactions is needed to get a complete view of primate
      behaviour. Five major factors appear to most strongly influence primate water
      use: thermoregulation, display behaviour, range, diet and predation. The
      ecological and evolutionary implications of these factors are discussed for
      extant primates as well as the possible influence of water on hominin evolution.

PMID- 19864920
TI  - Outpatient hysteroscopy with combined local intracervical and intrauterine
      anesthesia.
AB  - BACKGROUND/AIMS: To evaluate the degree of pain during and after office
      hysteroscopy with combined intracervical and intrauterine anesthesia compared to
      intracervical anesthesia only. METHODS: We evaluated the amount of pain
      experienced during office hysteroscopy using combined local intracervical and
      intrauterine anesthesia, 10, 30, and 60 min after, and during endometrial biopsy
      prospectively in 37 infertile women (study group). We used a visual analog scale
      ranging from 0 to 10. Seventy-six women who received only intracervical
      anesthesia served as historical controls. RESULTS: The mean ages of patients in
      the control and study groups were comparable. Patients' perception of pain was
      significantly higher during endometrial biopsy than during or after hysteroscopy
      in the study patients (p < 0.01, 95% CI 0-3). The mean pain score in the control
      group was significantly higher than that in the study group during hysteroscopy
      (3.3 +/- 0.2 vs. 2.2 +/- 0.3; p < 0.05, 95% CI 0-2). However, there was no
      significant difference in the pain scores between the control and study groups
      during endometrial biopsy and 10, 30, and 60 min after the procedure. CONCLUSION:
      Endometrial biopsy is associated with more pain than office hysteroscopy.
      Additional intrauterine anesthesia with 1% lidocaine significantly reduces pain
      sensation during office hysteroscopy.

PMID- 19864921
TI  - Defective particles can lead to underestimated antibody titers in virus
      neutralization tests.
AB  - OBJECTIVE: Stocks of RNA viruses often contain divergent mixtures of infectious
      and defective particles (DPs). Since the surface of both particles share the same
      immunoreactivity, differing ratios of these particles in stocks used for virus
      neutralization tests might alter the results. Here the impact of such off-target
      effects were measured. METHODS: To determine the relative content of DPs in 3
      stocks with high, medium and low titers of infectious virions, the amounts of
      nucleocapsid protein and viral RNA were quantified by Western blot and
      quantitative RT-PCR. Thereafter, stocks with different amount of DPs were used to
      determine the titer of neutralizing antibodies in serum from a convalescent
      Puumala virus-infected patient by a focus reduction neutralization test. RESULTS:
      The relative amount of DPs was at least 5-fold higher in the stock with the
      lowest titer compared to the stock with the highest. Stocks with lower levels of
      DPs led to higher antibody titers compared to the analysis performed with stocks
      containing higher levels of DPs. CONCLUSION: These results imply that DPs in
      virus stocks should be considered when performing virus neutralization tests to
      quantify neutralizing antibodies.

PMID- 19864922
TI  - Novel hepatitis B virus subgenotype in the southern Yunnan Province of China.
AB  - Hepatitis B virus (HBV) infection is highly prevalent in China. To identify the
      genotypes of HBV in the southern Yunnan Province of China, full-length HBV
      genomes were extracted from 1 Dai and 4 Hani HBV carriers and linked with the pMD
      T-18 vector. For each patient, 3-10 clones were sequenced directly and a
      consensus sequence was created. Genotypic and serotypic analysis revealed 4 HBV/B
      (2 B2 with adw2 and 2 new subgenotypes with ayw1) and 1 HBV/C (C1 with adrq+)
      genotypes. The divergences of the entire genome sequences of the new subgenotype
      were 0-0.9% and 2.99-6.48% between other known HBV/B. Divergences in other coding
      regions revealed that it was more similar to B3 and B4 in the precore/core gene
      (2.02 and 2.09%, respectively), and similar to B3 and B5 in the preS1/S2/S gene
      (2.24 and 2.78%, respectively). Phylogenetic trees using the precore/core and X
      genes both revealed a new clad separating from the major trunk of genotype B with
      a 99% bootstrap value. These results show that the 2 consensus isolates are a
      mosaic of B3-B5, which we designated to subgenotype B6. Considering the
      geographical distances, the relationship between B6 and other HBV/B subgenotypes
      (B3-B5) and HBV evolution needs to be further studied.

PMID- 19864923
TI  - Quantitative analysis of amplitude-integrated electroencephalogram patterns in
      stable preterm infants, with normal neurological development at one year.
AB  - BACKGROUND: The amplitude-integrated EEG (aEEG) is feasible for monitoring
      cerebral activity in preterm infants. However, quantitative data on normal
      patterns in these infants are limited. OBJECTIVE: To study maturational aEEG
      changes in a cohort of stable preterm infants by automated quantification.
      METHODS: In a cohort of stable preterm infants with gestational age (GA) <32
      weeks and normal neurological follow-up at 1 year, weekly 4 h EEG recordings were
      performed. aEEG traces were obtained from channel C(3)-C(4). The upper margin
      amplitude (UMA), lower margin amplitude (LMA) and bandwidth (BW) were
      quantitatively calculated using an expert software system. In addition, the
      relative duration of discontinuous background pattern (discontinuous background
      defined as activity with LMA <5 microV, expressed as DC-%) was calculated.
      RESULTS: 79 aEEG recordings (4-6 recordings/infant) were obtained in 18 infants.
      Analysis of the first week recordings demonstrated a strong positive correlation
      between GA and LMA, while DC-% decreased significantly. Longitudinally, all
      infants showed increase of LMA. Multivariate analysis showed that GA and
      postnatal age (PA) both contributed independently and equally to LMA and DC-%. We
      found a strong correlation between postmenstrual age (GA + PA) and LMA and DC-%,
      respectively. CONCLUSION: To our knowledge, this is the first study where aEEG
      development was studied by automated quantification of aEEG characteristics in a
      cohort of stable preterm infants with a normal neurological development at 1 year
      of age. LMA and DC-% are simple quantitative measures of neurophysiologic
      development and may be used to evaluate neurodevelopment in infants.

PMID- 19864925
TI  - Long-chain polyunsaturated fatty acid composition of breast milk in pre-eclamptic
      mothers.
AB  - BACKGROUND: Maternal fatty acid nutrition during pregnancy and lactation
      determines the transfer of long-chain polyunsaturated fatty acids via the
      placenta and through human milk. Neural maturation of breast-fed infants is known
      to be linked to breast-milk long-chain polyunsaturated fatty acid concentrations.
      In spite of this, the fatty acid composition of breast milk in pre-eclamptic
      mothers is poorly understood. OBJECTIVES: To compare the fatty acid composition
      of breast milk of pre-eclamptic (n = 45) with normotensive (n = 85) mothers and
      examine the association of breast-milk fatty acids with plasma fatty acids.
      METHODS: Milk and plasma fatty acid methyl esters were prepared and analyzed by
      the modified method of Manku and colleagues using gas chromatography. RESULTS:
      Docosahexaenoic acid (DHA) concentrations were significantly increased (p < 0.01)
      in breast milk in spite of lower maternal plasma DHA concentrations (p < 0.05) in
      pre-eclamptic women. However, there was no difference in arachidonic acid levels
      between groups in spite of reduced maternal plasma arachidonic acid levels.
      CONCLUSIONS: The data suggest that in pre-eclampsia, the relation between plasma
      and milk DHA is altered. The resulting higher milk DHA concentrations are
      beneficial for infants.

PMID- 19864924
TI  - Pulmonary vascular endothelial growth factor expression and disaturated
      phospholipid content in a chicken model of hypoxia-induced fetal growth
      restriction.
AB  - BACKGROUND: Prenatal hypoxia is an important cause of intrauterine growth
      retardation that affects fetal lung maturation, although previous studies have
      rendered conflicting results. The fetal chicken model allows the study of the
      isolated effects of hypoxia during development. OBJECTIVES: We hypothesized that
      prenatal hypoxia would differentially affect surfactant synthesis, depending on
      timing and duration of hypoxia. Pulmonary vascular endothelial growth factor
      (VEGF) expression was analyzed as a possible link between oxygen sensing and
      surfactant production. METHODS: Fertilized White Leghorn eggs were incubated in
      normoxia, hyperoxia (60% O(2)) from day 15 or hypoxia (15% O(2)) from either day
      6 or day 15 of incubation. Whole lung disaturated phospholipids (DSPL) and mRNA
      expression of VEGF isoforms were quantified at day 16 and 19. RESULTS: Lung DSPL
      content increased approximately threefold between day 16 and 19 in control
      animals. Both hypoxia and hyperoxia from day 15 significantly increased DSPL
      content at day 19 versus control (103 +/- 22 and 116 +/- 18 vs. 81 +/- 15
      microg/mg protein, p < 0.01 and p < 0.001, respectively), while long-term hypoxia
      tended to decrease DSPL content (65 +/- 17 microg/mg protein, p = 0.056). No
      differences in DSPL content were observed at day 16. Short-term hypoxia
      transiently up-regulated VEGF146 1.5-fold at day 16 (p < 0.05). A similar trend
      was observed for VEGF122 (p = 0.058) and VEGF190 (p = 0.08), while no differences
      were present at day 19. CONCLUSIONS: Both prenatal hypoxia and hyperoxia induced
      during critical windows of lung development differentially modulate surfactant
      synthesis. Our data support the concept that fetal oxygen tension is a key signal
      in the regulation of the surfactant system.

PMID- 19864926
TI  - Cerebral amino acid profiles after hypoxia-reoxygenation and N-acetylcysteine
      treatment in the newborn piglet.
AB  - BACKGROUND: Neonatal hypoxia-ischemia (HI) is a common clinical occurrence.
      Recently, much evidence has been gathered to suggest that oxygen free radicals
      are implicated in the pathogenesis of hypoxia-reoxygenation injury through the
      initiation and propagation of toxic cascades including glutamate excitotoxicity
      and the manifestation of post-HI neurologic disorders. Following HI, excessive
      free radicals are formed and antioxidant defenses are diminished. N
      acetylcysteine (NAC) is a clinically available antioxidant and has been
      previously shown to reduce oxidative stress and scavenge free radicals in
      multiple models of brain injury. OBJECTIVES: Using an acutely instrumented swine
      model of neonatal hypoxia-reoxygenation, the objective of the present study was
      to examine the neurochemical effects of NAC administration in 5 brain regions
      exquisitely vulnerable to severe hypoxia. METHODS: In a blinded fashion, newborn
      piglets (1-4 d, 1.4-2.2 kg) were block randomized into surgical sham (SHAM),
      hypoxic control (HC) and NAC-treated (H-NAC) groups. Both HC and H-NAC piglets
      were subject to 2 h of alveolar hypoxia (paO(2) = 20-40 mm Hg) and then
      resuscitated with 100% O(2 )for 1 h followed by 21% for an additional 3 h.
      RESULTS: Our results show that two hours of severe hypoxemia causes metabolic
      acidosis and significant changes in cerebral amino acids including glutamate,
      aspartate and alanine, in all brain regions investigated including the cortex,
      basal ganglia and thalamus. The administration of NAC 10 min into the
      reoxygenation period and subsequently continued as an infusion, maintains post
      resuscitation amino acid neurochemistry at the levels observed in SHAM piglets.
      CONCLUSIONS: In newborn piglets that have sustained brain injury related to
      hypoxia/reoxygenation, the administration of NAC does not disrupt cerebral amino
      acid balance and maintains cerebral amino acid homeostasis.

PMID- 19864927
TI  - Maternal alcohol intake and offspring pulse wave velocity.
AB  - BACKGROUND: Intrauterine exposure to alcohol may affect cardiovascular
      development, increasing risk of cardiovascular malformations. Intrauterine
      exposure to light maternal alcohol intake has been reported to affect human
      umbilical arterial contractility, and adult sheep exposed in utero have had
      altered cerebrovascular reactivity. In human adults, alcohol intake affects
      arterial stiffness. OBJECTIVES: We investigated whether intrauterine exposure to
      alcohol was associated with childhood pulse wave velocity (PWV), a measure of
      arterial stiffness. METHODS: On postnatal day 4, mothers of 147 twin pairs born
      in Tasmania from 1991 to 1993 reported alcohol intake during each trimester of
      pregnancy. At 9 years, child PWV was assessed over carotid-femoral and femoral
      dorsalis pedis arterial segments by applanation tonometry. RESULTS: Carotid
      femoral PWV was 0.2 m/s (95% CI 0.06, 0.4) higher (indicating stiffer vessels) in
      children whose mothers drank alcohol in the 2nd trimester rather than abstained,
      after adjusting for potential confounding factors. A similar effect was not seen
      for femoral-dorsalis pedis PWV. Findings were independent of child blood pressure
      which correlated strongly with PWV. Alcohol intake varied little between
      trimesters, so it was not possible to assess the effect of timing of exposure.
      CONCLUSIONS: Carotid-femoral PWV in adults is predictive of cardiovascular
      morbidity and mortality. The degree of continuity between childhood and adulthood
      PWV is unknown, but as we found an association between prenatal alcohol exposure
      and carotid-femoral PWV at 9 years, a permanent change in vessel wall structure
      or function is possible. These findings need to be confirmed in other and larger
      cohorts, and mechanistic animal studies are needed.

PMID- 19864928
TI  - Prospective evaluation of intravitreal triamcinolone acetonide in serpiginous
      choroiditis.
AB  - OBJECTIVE: To evaluate intravitreal triamcinolone acetonide (IVTA) in unilateral
      serpiginous choroiditis with macular involvement with special reference to
      effectiveness of treatment and its side effects. METHODS: In this prospective
      nonrandomized, consecutive, interventional case series, IVTA was given in 8 eyes
      of 8 patients of unilateral active serpiginous choroiditis. Treatment was
      evaluated on both subjective and objective parameters: any improvement or
      stabilization of visual acuity, fundus and fluorescein angiography (FA) and
      central macular thickness on optical coherence tomography (OCT). RESULT: The
      treatment induced rapid remission clinically and vision improved or stabilized.
      Mean visual acuity improved from 0.93 +/- 0.21 LogMAR units at baseline to 0.36
      +/- 0.24 (p = 0.00) LogMAR units at 6 months. A 33.73% reduction in mean central
      macular thickness was observed at the 6-month follow-up from 294.63 +/- 17.84 to
      195.25 +/- 5.49 mum (p = 0.00). Lesions healed rapidly with FA and OCT proving
      the clinical observation. CONCLUSION: Intravitreal triamcinolone may prove to be
      a promising therapeutic approach as a rescue therapy in this recurrent sight
      threatening disorder by inducing rapid remission without the systemic side
      effects seen with systemic immunosuppression.

PMID- 19864929
TI  - Relation between axial length and ocular parameters.
AB  - PURPOSE: To investigate the relation between axial length (AL) and ocular
      parameters. METHODS: Measurements of ocular biometric parameters were performed
      with an optical biometer, pachymeter, optical coherence tomography, and an
      automatic refractometer. AL, refractive error (RE), central corneal thickness,
      anterior chamber depth (ACD), corneal curvature (CC), white-to-white distance
      (WWD), and retinal nerve fiber layer (RNFL) thickness were measured. AL was
      evaluated in relation to ocular parameters. The Pearson correlation coefficient
      (r) was used to statistically evaluate each scattergram. RESULTS: With elongation
      of the AL, the mean RE (r = -0.790, p < 0.001), CC (r = -0.444, p < 0.001), and
      RNFL thickness (r = -0.306, p < 0.001) all decreased, while the mean ACD (r =
      0.506, p < 0.001) and WWD (r = 0.279, p < 0.001) increased. CONCLUSIONS: In
      shorter eyes, there was a tendency toward hyperopia, a steeper cornea, and a
      thicker RNFL, and in longer eyes toward myopia, a flatter cornea, and a thinner
      RNFL.

PMID- 19864930
TI  - Corneal endothelial cell loss after penetrating keratoplasty in relation to
      preoperative recipient endothelial cell density.
AB  - AIM: Our purpose was to assess recipient endothelial cell density and
      trephination diameter as predictive factors for corneal endothelial cell density
      after penetrating keratoplasty (PKP). METHODS: Forty-eight eyes showing
      keratoconus (group I, with sufficient recipient endothelial cell density) and 42
      eyes demonstrating bullous keratopathy or Fuchs' dystrophy (group II, with
      insufficient recipient endothelial cell density) were included in this
      retrospective study. The endothelial cell density after PKP was assessed over 2
      years. RESULTS: Chronic endothelial cell loss was significantly higher in group
      II than in group I patients at all follow-up times >3 months (p < 0.05). In group
      II patients, an inverse correlation between endothelial cell loss and trephine
      diameter was observed. CONCLUSION: This study shows that recipient endothelial
      cell density is a risk factor for increased endothelial cell loss following PKP.
      In patients with insufficient endothelial cell density, a large trephine size
      could reduce chronic endothelial cell loss.

PMID- 19864931
TI  - Birth defects following exposure to efavirenz-based antiretroviral therapy during
      pregnancy: a study at a regional South African hospital.
AB  - OBJECTIVES: To determine the prevalence and type of birth defects among infants
      following exposure to efavirenz-based antiretroviral therapy (EFV-based ART)
      during pregnancy. METHODS: A Pregnancy Registry was established to enable
      prospective follow-up of women taking EFV-based ART. In women who conceived on
      EFV-based ART, EFV was switched with another drug if they presented during the
      first trimester but was continued if they presented at or after 14 weeks'
      gestation. Pregnant women needing lifelong ART were commenced on EFV-based ART
      from 14 weeks' gestation onwards. Infants were followed up for 6 weeks after
      birth. RESULTS: Between January 2006 and December 2008, 623 ART-naive pregnant
      women initiated EFV-based ART in the second/third trimester and 195 women
      conceived on EFV-based ART. Birth defects were observed in 16 of 623 live births
      [2.6%; 95% confidence interval (CI) 1.5-4.2] and in six of 184 live births (3.3%;
      95% CI 1.2-7.0) from women exposed to EFV in the second/third trimester and first
      trimester, respectively. The prevalence of birth defects was not significantly
      different between the first and second/third trimester EFV exposure (prevalence
      ratio 1.27; 95% CI 0.50-3.20; P = 0.301). CONCLUSION: No significant increase in
      the prevalence of birth defects following exposure to EFV-based ART in the first
      trimester was observed in this cohort. However, the limited number of first
      trimester EFV-exposed infants precludes definitive conclusions on the
      teratogenicity or safety of EFV.

PMID- 19864932
TI  - Adenovirus vector-specific T cells demonstrate a unique memory phenotype with
      high proliferative potential and coexpression of CCR5 and integrin alpha4beta7.
AB  - BACKGROUND: The Step Study was a randomized trial to reduce HIV infection through
      vaccination with an adenovirus type 5 (Ad5)-based gag/pol/nef construct; analysis
      following early cessation of the trial revealed an excess of HIV seroconversion
      in Ad5 seropositive men. This led to the suggestion that the Ad based vector may
      boost the number of CD4 chemokine receptor 5 (CCR5) T cells, target cells for HIV
      infection. OBJECTIVES: We sought to determine the immunophenotype and
      proliferative capacity of Ad5-specific T cells in the peripheral blood of adult
      donors to determine whether stimulation with replication defective Ad5 vectors
      could result in the significant expansion of a CD4 CCR5 T-cell subset. METHODS:
      Ad5-specific T cells were identified in the peripheral blood of healthy donors by
      interferon-gamma secretion assay and proliferative response was measured by
      carboxyfluorescein succinimidyl ester labelling. Cells were analyzed by flow
      cytometry to determine T-cell differentiation marker, CCR5 and alpha4beta7
      expression on memory and proliferated cells. RESULTS: Ad5-specific CD4 T cells
      within healthy adult donors exhibit a unique minimally differentiated memory
      phenotype with coexpression of CD45RA, CD45RO and CCR7. Stimulation with Ad
      vector leads to rapid expansion in vitro and a switch to an effector memory
      phenotype. Both short-term reactivated and proliferating Ad5-specific CD4 T cells
      express the HIV coreceptor CCR5 and the HIV gp120-binding integrin alpha4beta7.
      CONCLUSION: Ad5-specific T cells demonstrate a phenotype and proliferative
      potential that would support HIV infection; these results are pertinent to the
      findings of the Step Study and future use of Ad5 as a vaccine vector.

PMID- 19864934
TI  - Computed tomography versus water-soluble contrast swallow in the detection of
      intrathoracic anastomotic leak complicating esophagogastrectomy (Ivor Lewis): a
      prospective study in 97 patients.
AB  - PURPOSE: Water-soluble contrast swallow (CS) is usually performed before
      refeeding for anastomosis assessment after esophagectomy with intrathoracic
      anastomosis but the sensitivity of CS is low. Another diagnostic approach is
      based on analysis of computed tomography (CT) scan with oral contrast and of CT
      mediastinal air images. We undertook to compare them prospectively. METHODS:
      Ninety-seven patients with an esophageal carcinoma operated by intrathoracic
      anastomosis were included prospectively in a study based on a CT scan at
      postoperative day 3 (without oral and intravenous contrast) and CT scan and CS at
      day 7. CT scan analysis consisted of assessing contrast and air leakage. In case
      of doubt, an endoscopy was done. RESULTS: A diagnosis of anastomotic leak was
      made in 13 patients (13.4%), in 2 cases before day 7 and in 3 beyond day 7. At
      day 3, 94 CT scans were performed, but the diagnostic value was poor. In 95
      patients with both CS and CT scan at day 7, CS disclosed a leak in 5 of 11, and
      CT scan was abnormal in 8 of 11. Leakage of contrast and/or presence of
      mediastinal gas had the best negative predictive value (95.8%). Endoscopy was
      done in 16 patients with only mediastinal gas at day 7 CT scan. It disclosed a
      normal anastomosis in 11, fibrin deposits in 4, and a leak in 1. CONCLUSIONS: In
      comparison with CS only, CT at day 7 improves the sensitivity and negative
      predictive value for diagnosing an anastomotic leak. In case of doubt endoscopy
      is advisable. This approach provides an accurate assessment of the anastomosis
      before refeeding.

PMID- 19864933
TI  - Development of a didanosine genotypic resistance interpretation system based on
      large derivation and validation datasets.
AB  - OBJECTIVE: To assess the genotypic determinants of the virological response to
      didanosine (ddI) in HIV-infected patients. METHODS: The Forum database on ddI was
      randomly divided into a derivation set (n = 1000) and a validation set (n = 453).
      Linear regression models and bootstrap sampling were used to select resistance
      mutations and to estimate their resistance scores. Linear regression models,
      accounted for the censoring of viral load measurements due to assay lower limits,
      of the week 8 reduction in viral load from baseline were adjusted for baseline
      viral load, the exact number of weeks between baseline and the week 8 viral load
      measurements, and the Stanford genotypic sensitivity score. RESULTS: The ddI
      resistance mutations and their resistance scores based on the derivation set were
      as follows: M41L (score of 14), T69D (24), D123S (40), T139M (54), I180V (53),
      M184V (-12), V189I (55), Q207K (37), L210W (25), and T215Y (eight). The total
      score is obtained by adding the individual scores. Viruses with scores of 19 or
      less, 20-59, and 60 or more are considered sensitive, intermediate, and
      resistant, respectively. In the validation set, respectively, 58.7, 36.9, and
      4.4% of viruses were predicted to be sensitive, intermediate, and resistant to
      ddI. The observed viral load reductions at week 8 were, respectively, 1.51 log10
      copies/ml [interquartile range (IQR) 1.26-1.76] (P = 0.0001 versus resistant),
      1.11 (0.94-1.30) (P = 0.0077 versus sensitive), and 0.46 (0.32-0.74) (P = 0.0079
      versus intermediate). CONCLUSION: We developed a genotypic resistance score for
      didanosine including four mutations never previously used.

PMID- 19864935
TI  - An analysis of the French multicentre experience of fenestrated aortic
      endografts: medium-term outcomes.
AB  - PURPOSE: To evaluate the medium-term outcomes following aortic aneurysm repair
      utilizing fenestrated endografts performed in 13 French academic centers.
      MATERIALS AND METHODS: A retrospective analysis of prospectively collected data.
      All patients had asymptomatic aneurysms involving or close to the visceral
      bearing abdominal aorta and were judged to be at high-risk for open surgical
      repair. Fenestrated endografts were designed using computed tomography
      reconstructions performed on three-dimensional workstations. The procedures were
      conducted under fluoroscopic control by experienced endovascular teams. All
      patients were evaluated with computed tomography, duplex ultrasound, and plain
      film radiograph at discharge, 6, 12, 18, and 24 months, and annually thereafter.
      RESULTS: Eighty patients (78 males) were treated over 44 months (May 2004-January
      2008). Median age and aneurysm size were 78 years (range: 48-90 years) and 59 mm
      (range: 47-82 mm), respectively. A total of 237 visceral vessels were perfused
      through a fabric fenestration (median of 3 per patient). One early conversion to
      open surgery was required. Completion angiography showed that 234 of 237 (99%)
      target vessels were patent. Two patients (2.5%) died within 30 days of device
      implantation. Predischarge imaging identified 9 (11%) endoleaks: 3 type I, 5 type
      II, and 1 type III. The median duration of follow-up was 10 months (range: 1-38
      months). No aneurysms ruptured or required open conversion during the follow-up
      period. Four of 78 (5%) died during follow-up (actuarial survival at 24 months
      92%), none of these deaths were aneurysm related. Aneurysm sac size decreased by
      more than 5 mm in 33%, 53%, and 58% at 6, 12, and 18 months, respectively. One
      patient had sac enlargement within the first year, associated with a persistent
      type II endoleak. In-stent stenoses or occlusion affected 4 renal arteries.
      Secondary procedures were performed in 8 patients (10%) during follow-up, 5 to
      correct endoleaks and 3 to correct threatened visceral vessels. CONCLUSIONS: The
      use of endovascular prostheses with graft material incorporating the visceral
      arteries is safe in high risk patients with high risk aneurysms. In the medium
      term it is effective in preventing rupture. However, meticulous follow-up to
      assess sac behavior and visceral ostia is critical to ensure optimal results.

PMID- 19864936
TI  - Clinical significance of acellular mucin in rectal adenocarcinoma patients with a
      pathologic complete response to preoperative chemoradiation.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence and
      prognostic significance of acellular mucin within resected specimens of rectal
      cancer patients with a pCR following preoperative chemoradiation. SUMMARY
      BACKGROUND DATA: The presence of acellular mucin pools in the resected specimens
      of patients with a complete response to preoperative chemoradiation is frequently
      reported as a marker of treatment effect. The clinical significance of the
      presence of acellular mucin with respect to local recurrence and survival
      outcomes is unknown. METHODS: Data from a rectal cancer database was used to
      analyze 562 patients with nonmetastatic rectal adenocarcinoma treated between
      1989 and 2004. The presence or absence of acellular mucin within the specimen was
      identified by the surgical pathology reports and confirmed by re-examination of
      H&E sections of surgical specimens. RESULTS: Among the 562 patients, 100 patients
      (18%) had pCR. Acellular mucin was present in 27 (27%) of the 100 patients with
      pCR. The median follow-up interval was 87 months (range, 1-198 months). Local and
      distant failures occurred in 0 and 2 patients with acellular mucin, and in 1 and
      6 patients without acellular mucin, respectively. The actuarial 7-year overall
      survival rates were 85% for patients with acellular mucin and 92% for patients
      without acellular mucin (P = 0.954). The actuarial 7-year disease-free survival
      rates were 81% and 87% (P = 0.764) and the 7-year freedom from relapse rates were
      93% and 91% (P = 0.881) in patients with and without acellular mucin,
      respectively. CONCLUSIONS: Acellular mucin is present within 27% of resected
      specimens in rectal cancer patients with a pCR after preoperative chemoradiation.
      However, the presence of acellular mucin has no prognostic significance.

PMID- 19864937
TI  - Impact of antithrombin III concentrates on portal vein thrombosis after
      splenectomy in patients with liver cirrhosis and hypersplenism.
AB  - OBJECTIVE: The aim of this study was to determine the role of antithrombin III
      (AT-III) in portal vein thrombosis (PVT) after splenectomy in cirrhotic patients.
      SUMMARY BACKGROUND DATA: There is no standard treatment for PVT after splenectomy
      in liver cirrhosis. METHODS: A total of 50 consecutive cirrhotic patients who
      underwent laparoscopic splenectomy for hypersplenism were enrolled into this
      study. From January 2005 to December 2005, 25 cirrhotic patients received no
      prophylactic anticoagulation therapy after the operation (AT-III [-] group). From
      January 2006 to July 2006, 25 cirrhotic patients received prophylactic
      administration of AT-III concentrates (1500 U/d) on postoperative day (POD) 1, 2,
      and 3 (AT-III [+] group). RESULTS: In AT-III (-) group, 9 (36.0%) patients
      developed PVT up to POD 7, and risk factors for PVT were identified as: low
      platelet counts, low AT-III activity, and increased spleen weight. Although there
      were no significant differences in the clinical characteristics, including the
      above risk factors, between the 2 groups, only 1 (4.0%) patient developed PVT on
      POD 30 in AT-III (+) group, and the incidence of PVT was significantly lower than
      in AT-III (-) group (P = 0.01). In AT-III (-) group, AT-III activity was
      significantly decreased from POD 1 to POD 7, as compared with the preoperative
      level, whereas AT-III concentrates prevented the postoperative decrease in AT-III
      activity. CONCLUSIONS: These results demonstrate that low AT-III activity and
      further decreases in this activity are associated with PVT after splenectomy in
      cirrhotic patients, and that treatment with AT-III concentrates is likely to
      prevent the development of PVT in these patients.

PMID- 19864938
TI  - In vivo evaluation of bacterial infection involving morphologically different
      surgical meshes.
AB  - OBJECTIVE: To study the influence of morphology of surgical meshes on the course
      of bacterial infection under the influence of the host immune system in an in
      vivo chronic bacterial infection model. BACKGROUND: The use of prosthetic meshes
      has increased dramatically the last decades in abdominal wall reconstructive
      surgery. Whereas infection is becoming a more frequent complication, attention is
      increasingly drawn to the influence of the surgeon's mesh choice on the course of
      this complication. METHODS: Samples of 6 often applied surgical meshes were
      contaminated with a bioluminescent strain of Staphylococcus aureus and implanted
      subcutaneously in an immunocompetent BALB/c mouse. The intensity and the
      spreading of bioluminescence (ie, p/s/cm/sr) were analyzed non-invasively in vivo
      during a 10-day follow-up period. RESULTS: Over the course of infection,
      multifilament polypropylene and hydrophobic materials showed a significantly
      higher persistence of bacteria as well as spreading of infection compared to all
      other meshes. In contrast, infection resolved in almost all animals with a low
      weight polyester mesh. CONCLUSION: The results of this study are in accordance
      with circumstantial evidence from limited clinical reports on infection involving
      surgical meshes and suggest that multifilament and hydrophobic meshes
      significantly increase bacterial persistence or spreading in the infected area in
      contrast to monofilament polypropylene and lightweight meshes. Therefore, the
      surgeon should consider this outcome when choosing a mesh graft for limiting
      infection in abdominal wall repair.

PMID- 19864939
TI  - Intra-abdominal pressure measurement method via the urinary-tube: bedside
      validation of a biomechanical model integrating urine column height and bladder
      urinary volume.
AB  - BACKGROUND: The objective of this work was to demonstrate the possibility of
      accurately measuring intra-abdominal pressure (IAP) by using a common urine
      drainage bag (U-Tube) as a hydrostatic column of measurement. This has been done
      by integrating urine column height (h) and bladder urinary volume (BUV) in the
      IAP measurement method. METHOD: Seventy-eight newly admitted patients in a 22 bed
      university hospital intensive care unit (ICU) were studied. Two U-Tube IAP
      measurement methods were compared with the "Gold-standard" closed-system repeated
      measurement technique with bladder pressure transducer: U-Tube method I, where h
      (in cm) alone assesses IAP (in cm H2O) and U-Tube method II, integrating BUV
      according to a basic biomechanical model of bladder wall compliance to give a
      more accurate IAP estimation. RESULTS: Correlation rate using linear regression
      analysis was better between the Gold standard method and method II than method I
      with R = 0.901, P < 0.0001 and R = 0.682, P < 0.0001, respectively. For method
      II, Bland-Altman analysis showed a mean bias of -1.0 +/- 0.1 mm Hg (limits of
      agreement -3.4-1.4, percentage error +/-7.7%). Area under the receiver operator
      characteristics curves to screen intra-abdominal hypertension (IAP >or=12 mm Hg)
      was significantly greater with method II than with method I: 0.99 versus 0.93, P
      < 0.05; sensitivity and specificity of method II were 95% and 98%, respectively.
      CONCLUSION: By integrating urine column height and BUV in the measurement method,
      it may be conceivable to screen IAH at the bedside via a U-Tube in ICU; bladder
      wall compliance should be estimated to avoid the emergence of false-positive
      subjects due to the possible occurrence of bladder wall compliance alteration
      before or during the ICU stay.

PMID- 19864940
TI  - Intraoperative touch imprint and frozen section analysis of sentinel lymph nodes
      after neoadjuvant chemotherapy for breast cancer.
AB  - OBJECTIVE: To evaluate the accuracy of touch imprint and frozen section analysis
      of sentinel nodes after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA:
      Intraoperative evaluation of the sentinel node can determine the need for
      axillary dissection at the time of initial operation and therefore spare the
      patient a second operation. Little data, however, exists on the accuracy of
      intraoperative evaluation of sentinel nodes after neoadjuvant chemotherapy.
      METHODS: A retrospective chart review was performed of all sentinel node
      procedures for breast cancer from 2004 to 2008 at a single institution. The
      sentinel node procedure was done before (no-NACT) chemotherapy in 107 patients
      and 37 had the procedure after neoadjuvant (NACT) chemotherapy. Intraoperative
      analysis of sentinel nodes was performed using touch imprint and frozen section
      techniques. RESULTS: In the no-NACT group, intraoperative assessment by touch
      imprint analysis had 61% sensitivity, 100% specificity, and 87% accuracy. Frozen
      section analysis was similar with 74% sensitivity, 100% specificity, and 90%
      accuracy. In the NACT group, touch imprint analysis had 79% sensitivity, 100%
      specificity, and 90% accuracy. Frozen section analysis was again similar with 74%
      sensitivity, 100% specificity, and 83% accuracy. When the no-NACT group and the
      NACT group were compared, both frozen section and touch imprint analysis had
      similar sensitivity, specificity, and accuracy. CONCLUSIONS: Intraoperative
      evaluation of sentinel nodes with touch imprint and frozen section analysis in
      patients treated with neoadjuvant chemotherapy showed acceptable sensitivity,
      specificity, and accuracy. Nearly all of the misses in intraoperative evaluation
      were in patients with micrometastases.

PMID- 19864941
TI  - Effects of allogeneic leukocytes in blood transfusions during cardiac surgery on
      inflammatory mediators and postoperative complications.
AB  - OBJECTIVE: To investigate whether the higher prevalence of postoperative
      complications in cardiac surgery after transfusion of leukocyte-containing red
      blood cells can be related to inflammatory mediators. DESIGN: Analysis of
      inflammatory markers interleukin-6, interleukin-10, interleukin-12, and
      procalcitonin in patients participating in a randomized trial comparing leukocyte
      depleted with leukocyte-containing, buffy-coat-depleted red blood cells. SETTING:
      Two university-affiliated hospitals in the Netherlands. SUBJECTS: A total of 346
      patients undergoing cardiac valve surgery with a complete series of pre- and
      postoperative blood samples. MEASUREMENTS AND MAIN RESULTS: There were no
      differences in the cytokines and procalcitonin concentrations between both study
      arms when the patients arrived in the intensive care unit. In subgroups, patients
      who received zero to three red blood cell transfusions showed similar cytokine
      concentrations in both study arms, whereas patients with > or = 4 red blood cell
      transfusions had significantly higher interleukin-6 concentrations in the
      leukocyte-containing, buffy-coat-depleted red blood cell group. Patients who
      developed postoperative infections and multiple organ dysfunction syndrome
      showed, respectively, increased concentrations of interleukin-6 and interleukin
      12 in the leukocyte-containing, buffy-coat-depleted, red blood cell group. The
      interaction tests in these subgroups showed significantly different reaction
      patterns in the leukocyte-containing, buffy-coat-depleted red blood cell group
      compared with leukocyte-depleted red blood cell group for interleukin-6 and
      interleukin-12. Multivariate analysis showed a high interleukin-6 concentration
      with multiple organ dysfunction syndrome and both high interleukin-6 and
      interleukin-10 concentrations with hospital mortality. CONCLUSIONS: Allogeneic
      leukocyte-containing blood transfusions compared with leukocyte-depleted blood
      transfusions induce dose-dependent significantly higher concentrations of
      proinflammatory mediators in the immediate postoperative period after cardiac
      surgery. High concentrations of interleukin-6 are strong predictors for
      development of multiple organ dysfunction syndrome, whereas both interleukin-6
      and interleukin-10 are associated with hospital mortality. These findings suggest
      that leukocyte-containing red blood cells interfere with the balance between
      postoperative proinflammatory response, which may further affect the development
      of complications after cardiac surgery.

PMID- 19864943
TI  - When is genetic testing useful in patients suspected to have inherited cardiac
      arrhythmias?
AB  - PURPOSE OF REVIEW: In this article, we will review the appropriate use of genetic
      testing in those patients suspected to have inherited arrhythmogenic diseases,
      with specific focus on the indications for testing and the expected probability
      of positive genotyping. RECENT FINDINGS: Important advances have been made in the
      identification of new genes, associated mutations, and polymorphisms that
      modulate susceptibility of acquired arrhythmias. We will examine the most recent
      advances relevant to the rational application of genetic analysis, guided by
      genotype-phenotype correlations derived from disease and patient-specific
      evaluation, as well as discussing novel technologies and recently published cost
      effectiveness data. SUMMARY: Genetic analysis can be performed to identify the
      molecular substrate in those patients suspected to be affected by an inherited
      arrhythmogenic disease; however, the clinical usefulness of this information is
      often not straightforward. We hope to emphasize the concept that there is a
      significant difference in the impact of genetic testing within the various
      arrhythmogenic disorders, and the benefit of accessing genetic testing is not the
      same in all patients. The resultant integration between the expected yield of
      genetic screening and cost may allow the formation of criteria to prioritize
      access for those who could derive the most clinical benefit.

PMID- 19864942
TI  - Assessment of the impedance cardiogram recorded by an automated external
      defibrillator during clinical cardiac arrest.
AB  - OBJECTIVE: To assess the impedance cardiogram recorded by an automated external
      defibrillator during cardiac arrest to facilitate emergency care by lay persons.
      Lay persons are poor at emergency pulse checks (sensitivity 84%, specificity
      36%); guidelines recommend they should not be performed. The impedance cardiogram
      (dZ/dt) is used to indicate stroke volume. Can an impedance cardiogram algorithm
      in a defibrillator determine rapidly circulatory arrest and facilitate prompt
      initiation of external cardiac massage? DESIGN: Clinical study. SETTING:
      University hospital. PATIENTS: Phase 1 patients attended for myocardial perfusion
      imaging. Phase 2 patients were recruited during cardiac arrest. This group
      included nonarrest controls. INTERVENTIONS: The impedance cardiogram was recorded
      through defibrillator/electrocardiographic pads oriented in the standard cardiac
      arrest position. MEASUREMENTS AND MAIN RESULTS: Phase 1: Stroke volumes from
      gated myocardial perfusion imaging scans were correlated with parameters from the
      impedance cardiogram system (dZ/dt(max) and the peak amplitude of the Fast
      Fourier Transform of dZ/dt between 1.5 Hz and 4.5 Hz). Multivariate analysis was
      performed to fit stroke volumes from gated myocardial perfusion imaging scans
      with linear and quadratic terms for dZ/dt(max) and the Fast Fourier Transform to
      identify significant parameters for incorporation into a cardiac arrest
      diagnostic algorithm. The square of the peak amplitude of the Fast Fourier
      Transform of dZ/dt was the best predictor of reduction in stroke volumes from
      gated myocardial perfusion imaging scans (range = 33-85 mL; p = .016). Having
      established that the two pad impedance cardiogram system could detect differences
      in stroke volumes from gated myocardial perfusion imaging scans, we assessed its
      performance in diagnosing cardiac arrest. Phase 2: The impedance cardiogram was
      recorded in 132 "cardiac arrest" patients (53 training, 79 validation) and 97
      controls (47 training, 50 validation): the diagnostic algorithm indicated cardiac
      arrest with sensitivities and specificities (+/- exact 95% confidence intervals)
      of 89.1% (85.4-92.1) and 99.6% (99.4-99.7; training) and 81.1% (77.6-84.3) and
      97% (96.7-97.4; validation). CONCLUSIONS: The impedance cardiogram algorithm is a
      significant marker of circulatory collapse. Automated defibrillators with an
      integrated impedance cardiogram could improve emergency care by lay persons,
      enabling rapid and appropriate initiation of external cardiac massage.

PMID- 19864944
TI  - Anger and ventricular arrhythmias.
AB  - PURPOSE OF REVIEW: Although anecdotal evidence has long suggested links between
      emotion and ventricular arrhythmia, more recent studies have prospectively
      demonstrated the arrhythmogenic effects of anger, as well as mechanisms
      underlying these effects. RECENT FINDINGS: Epidemiological studies reveal that
      psychological stress increases sudden death, as well as arrhythmias, in patients
      with implantable cardioverter-defibrillators, in populations during emotionally
      devastating disasters such as earthquake or war. Diary-based studies confirm that
      anger and other negative emotions can trigger potentially lethal ventricular
      arrhythmias. Anger alters electrophysiological properties of the myocardium,
      including T-wave alternans, a measure of heterogeneity of repolarization,
      suggesting one mechanistic link between emotion and arrhythmia. Pilot studies of
      behavioral interventions have shown promise in decreasing arrhythmias in patients
      with implantable cardioverter-defibrillators. SUMMARY: Anger and other strong
      emotions can trigger polymorphic, potentially life-threatening ventricular
      arrhythmias in vulnerable patients. Through autonomic changes including increased
      sympathetic activity and vagal withdrawal, anger leads to increases in
      heterogeneity of repolarization as measured by T-wave alternans, known to be
      associated with arrhythmogenesis, as well as increasing inducibility of
      arrhythmia. Further delineation of mechanisms linking anger and arrhythmia, and
      of approaches to decrease the detrimental effects of anger and other negative
      emotions on arrhythmogenesis, are important areas of future investigation.

PMID- 19864946
TI  - Effects of sepsis on neutrophil chemotaxis.
AB  - PURPOSE OF REVIEW: Neutrophil recruitment to sites of infection is a critical
      element of the innate immune response. In patients with sepsis, this response is
      dysregulated, with exuberant inflammation being followed by a state of profound
      immune suppression, including inhibition of neutrophil recruitment. This review
      examines mechanisms underlying suppression of neutrophil migration during sepsis.
      RECENT FINDINGS: Mechanisms governing neutrophil chemotactic function in sepsis
      are complex. Bacterial products, cytokines, and chemokines can modulate
      neutrophil migratory responses during sepsis via induction of cytoskeletal
      changes, inhibition of polymorphonuclear leukocyte (PMN)-endothelial cell
      interactions, and alterations in G protein-coupled receptor expression or
      signaling. Impaired chemotactic responses can occur as a result of dysregulated
      PMN Toll-like receptor signaling. Other recently identified inhibitory mechanisms
      include exposure to elevated temperatures, activation of the anti-inflammatory
      nuclear transcription factor peroxisome proliferator-activated receptor-gamma,
      and suppression of PMN-endothelial interactions due to nitric oxide and its
      metabolites. Finally, circulating microparticles released in sepsis exert
      important immunomodulatory effects on PMN adherence and transmigration. SUMMARY:
      Neutrophil recruitment is a coordinated process that is altered at multiple
      stages during sepsis, culminating in defective innate immunity and increased risk
      of infection in these patients. Defining mechanisms involved and strategies to
      interrupt these deleterious responses requires further investigation.

PMID- 19864945
TI  - Recent developments and complexities in neutrophil transmigration.
AB  - PURPOSE OF REVIEW: As the migration of neutrophils from blood to inflamed tissues
      is an essential component of innate immunity and a key contributing factor to the
      pathogenesis of inflammatory disorders, this aspect of leukocyte biology
      continues to be a highly dynamic field of research. This review summarizes recent
      findings in this area, focusing on the mechanisms that mediate neutrophil
      transmigration, an area where significant progress has been made. RECENT
      FINDINGS: The topics to be covered will include responses that are prerequisite
      to neutrophil migration through venular walls, such as leukocyte luminal crawling
      and cellular and molecular changes in leukocytes and endothelial cells (e.g.
      formation of protrusions) that collectively support leukocyte transendothelial
      cell migration. Advances in both paracellular and transcellular neutrophil
      migration through endothelial cells will be discussed, addressing the associated
      roles and regulation of expression of endothelial cell luminal and junctional
      adhesion molecules. Beyond the endothelium, migration through the vascular
      pericyte coverage and basement membrane will be reviewed. SUMMARY: The
      unquestionable role of neutrophils in the development and progression of
      inflammatory conditions suggests that a better understanding of the tissue
      specific and stimulus-specific mechanisms that mediate this response may identify
      novel pathways that could be exploited for the development of more specific anti
      inflammatory interventions.

PMID- 19864948
TI  - Renal homeostasis and tubuloglomerular feedback.
AB  - PURPOSE OF REVIEW: We review some basic homeostatic principles that are
      frequently disregarded to provide boundary conditions to test any new theory
      containing new details. Homeostasis as applied to total body salt is discussed
      with a linear model for salt homeostasis that is extraordinarily simple wherein
      total body salt drives the salt excretion. The basics of tubuloglomerular
      feedback (TGF) and its implications for salt homeostasis are then reviewed.
      RECENT FINDINGS: Advances in the field discussed include new details on the
      apical and basolateral transport of sodium chloride (NaCl) in the macula densa
      cells during TGF response, direct evidence of contribution of TGF to renal
      autoregulation and the description of vasodilatory adenosine A2b receptors in the
      'efferent' TGF response. Finally, recent information about the role of proximal
      tubular microvilli as mechanosensors in the flow-dependent tubular reabsorption
      as a mechanism to explain glomerulotubular balance is reviewed. SUMMARY:
      Notwithstanding the complexity of salt balance at a molecular level, the overall
      salt homeostasis is simple. Various natritropic nerves and hormones stabilize any
      disturbance in salt balance. A change in glomerular filtration rate (GFR) brought
      about by these natritropes will be partially counteracted by the impact of TGF on
      nephron function. Thus, by stabilizing GFR, TGF reduces the usefulness of GFR as
      an instrument of salt balance, and lessens the efficiency of salt homeostasis.

PMID- 19864947
TI  - Regulation of circadian blood pressure: from mice to astronauts.
AB  - PURPOSE OF REVIEW: Circadian variation is commonly seen in healthy people;
      aberration in these biological rhythms is an early sign of disease. Impaired
      circadian variation of blood pressure (BP) has been shown to be associated with
      greater target organ damage and with an elevated risk of cardiovascular events
      independent of the BP load. The purpose of this review is to examine the
      physiology of circadian BP variation and propose a tripartite model that explains
      the regulation of circadian BP. RECENT FINDINGS: The time-keeper in mammals
      resides centrally in the suprachiasmatic nucleus. Apart from this central clock,
      molecular clocks exist in most peripheral tissues including vascular tissue and
      the kidney. These molecular clocks regulate sodium balance, sympathetic function
      and vascular tone. A physiological model is proposed that integrates our
      understanding of molecular clocks in mice with the circadian BP variation among
      humans. The master regulator in this proposed model is the sleep-activity cycle.
      The equivalents of peripheral clocks are endothelial and adrenergic functions.
      Thus, in the proposed model, the variation in circadian BP is dependent upon
      three major factors: physical activity, autonomic function, and sodium
      sensitivity. SUMMARY: The integrated consideration of physical activity,
      autonomic function, and sodium sensitivity appears to explain the physiology of
      circadian BP variation and the pathophysiology of disrupted BP rhythms in various
      conditions and disease states. Our understanding of molecular clocks in mice may
      help to explain the provenance of blunted circadian BP variation even among
      astronauts.

PMID- 19864950
TI  - Controversy surrounding the role for routine central lymph node dissection for
      differentiated thyroid cancer.
AB  - PURPOSE OF REVIEW: Differentiated thyroid cancer (DTC), with a rapidly increasing
      incidence is the most common endocrine malignancy, but with generally favorable
      survival. Total thyroidectomy with 'therapeutic' cervical lymph node dissection
      for involved lymph nodes is the standard of care. A more controversial topic is
      whether routine 'prophylactic' central lymph node dissection (CLND) in patients
      without evidence of lymph node metastasis should be performed in patients with
      DTC, as suggested by several recent management guidelines. RECENT FINDINGS: A
      number of retrospective studies suggest that regional lymph node metastases are
      associated with tumor recurrence and adverse survival. CLND is associated with a
      higher rate of postoperative athyroglobulinemia and may modify the indications
      for radioactive iodine treatment. Current guidelines from the American Thyroid
      Association suggest that prophylactic CLND may be performed for papillary thyroid
      cancer, especially for advanced tumors (T3 and T4). SUMMARY: Recent studies and
      the arguments for and against prophylactic CLND are reviewed. There is currently
      a trend toward more aggressive surgical therapy, including prophylactic CLND and
      avoidance of radioactive iodine treatment for DTC, when appropriate. Randomized
      prospective controlled trials are lacking at this point to determine the role of
      prophylactic CLND in the management of DTC.

PMID- 19864949
TI  - New role for plasmin in sodium homeostasis.
AB  - PURPOSE OF REVIEW: Hypertension and edema are clinical manifestations of the
      extracellular volume expansion generated by abnormal renal sodium handling.
      Perturbations in epithelial sodium channel (ENaC) activity disrupt volume
      homeostasis. ENaC activity can be enhanced by proteases that cleave its long
      extracellular domains. Recent evidence suggests that this mechanism may be
      involved in individuals with volume overload and proteinuria. RECENT FINDINGS:
      Several observations indicate a link between proteinuria and hypertension, with
      proteinuria preceding and predicting the onset of incident hypertension in some
      individuals. Recently, enhanced cleavage of ENaC's extracellular loops was
      identified in kidney tissue of proteinuric mice. Plasmin, a serine protease known
      for its role in fibrinolysis, has been implicated as an activator of ENaC in
      proteinuric states as nephrotic urine activates ENaC expressed in a mouse
      collecting duct cell line, aprotinin-affinity precipitation of nephrotic urine
      abolishes its ability to activate ENaC, plasmin is a major component within
      aprotinin-affinity purified nephrotic urine and is absent in nonproteinuric
      urine, and plasmin activates ENaC by cleaving the extracellular loop of its gamma
      subunit. SUMMARY: Enhancement of ENaC activity by proteases represents a likely
      mechanism for extracellular volume overload relevant to some individuals with
      proteinuria. Proteases not normally found in the urine can enter the urinary
      space across damaged glomeruli and activate ENaC. Further understanding of this
      mechanism may guide targeted therapeutics in individuals with proteinuria, edema,
      and hypertension.

PMID- 19864951
TI  - Developments in the use of ultrasound for thyroid cancer.
AB  - PURPOSE OF REVIEW: This article reviews the recent developments in neck
      ultrasound for thyroid cancer published in the last 18 months, with emphasis on
      the emerging role of surgeon-performed ultrasound in clinical endocrine practice.
      RECENT FINDINGS: Ultrasound has evolved beyond the simple differentiation of
      solid and cystic thyroid nodules and their measurement. Although no single
      ultrasound feature has the highest accuracy in distinguishing between benign and
      malignant thyroid lesions, the combination of several ultrasound characteristics
      (e.g. hypoechogenicity, irregular borders and microcalcifications) within such
      thyroid nodules may have a stronger correlation for thyroid cancer. Based on
      these ultrasound features and risk for thyroid malignancy, the need for
      ultrasound-guided fine needle aspiration, preoperative staging, lymph node
      mapping and extent of surgery can subsequently be determined and performed.
      Furthermore, ultrasound has an additional value intraoperatively and in the
      postoperative surveillance of patients treated for thyroid cancer. Surgeon
      performed ultrasound has recently become indispensible in clinical practice where
      endocrine surgeons have integrated this versatile imaging modality in the
      evaluation and treatment of patients with thyroid cancer. SUMMARY: Ultrasound is
      an essential modality in the evaluation of thyroid malignancy. Surgeon-performed
      ultrasound has proved invaluable in the preoperative, intraoperative and
      postoperative setting. Future developments in ultrasound may lead to further
      improvement in the diagnostic accuracy of this modality.

PMID- 19864952
TI  - Rheumatic manifestations of hepatitis.
AB  - PURPOSE OF THE REVIEW: Rheumatic manifestations are commonly encountered in
      patients with hepatitis B virus (HBV) or C (HCV) infection. In this review the
      most common clinical rheumatic manifestations of HBV or HCV infection and their
      management will be critically presented with a special emphasis on the efficacy
      and safety of the new biologic agents. RECENT FINDINGS: Recent significant
      advances in the antiviral therapy of chronic hepatitis B and C as well as the
      emergence of new biologic therapies (anti-TNF agents, rituximab) for the
      treatment of rheumatic diseases have changed significantly the therapeutic
      approach for patients with rheumatic disorders in the setting of hepatitis B or
      C. For patients with hepatitis B, prophylactic antiviral therapy with oral
      antiviral agents (nucleoside or nucleotide analogues) is recommended for all
      cases in which immunosuppressive therapies are administered, whereas for severe
      hepatitis C-associated mixed cryoglobulinemia, a number of recent studies have
      shown the short-term safety and efficacy of rituximab. SUMMARY: Rheumatologists
      in collaboration with hepatologists have today an array of efficacious
      therapeutic options to explore for patients presenting with rheumatic disorders
      in the setting of a co-existent HBV or HCV infection. Appropriate pretreatment
      screening and close monitoring are essential for these difficult-to-treat
      patients.

PMID- 19864953
TI  - Recent progress in the genetics of Wegener's granulomatosis and Churg-Strauss
      syndrome.
AB  - PURPOSE OF REVIEW: Recently, numerous studies have been performed to elucidate
      the genetic background of Wegener's granulomatosis and Churg-Strauss syndrome
      (CSS). Many of these investigations suffer from low statistical power,
      inconsistent case classification and other error-prone study designs. The
      majority of these findings has to be considered preliminary, if not spurious. We
      summarize the most important and robust findings. RECENT FINDINGS: HLA-DPB1, the
      association of which with Wegener's granulomatosis has been discovered some years
      ago, is still the strongest and best replicated risk locus for this condition.
      Yet, no association is demonstrable for CSS, in which another HLA locus, HLA-DR,
      seems to be more important. Vice versa, a strong association with IL10 promotor
      polymorphisms was detected in CSS but not in a large Wegener's granulomatosis
      panel. Numerous other associations, including CTLA4, CD226 and copy number
      polymorphisms of FCGR3B still need further investigation, before reliable
      conclusions can be drawn. SUMMARY: In order to be able to evaluate critically the
      genetic background of Wegener's granulomatosis and CSS future projects should
      take into account several aspects of study design. These preconditions include
      sufficient numbers of cases (i.e. statistical power) and a clear-cut
      classification of these cases, thus allowing differentiated analyses of certain
      disease subgroups.

PMID- 19864954
TI  - Impact of visual cues on directional benefit and preference: Part I--laboratory
      tests.
AB  - OBJECTIVES: The purpose of the laboratory tests of the current investigation was
      to examine how visual cues impact directional (DIR) benefit and preference for
      the DIR microphone hearing aid (re: the omnidirectional [OMNI] microphone).
      Specifically, three hypotheses were examined: (1) the presence of visual cues
      would improve OMNI-aided performance to ceiling levels and therefore reduce DIR
      benefit and preference, (2) DIR benefit measured in the audiovisual (AV)
      condition could not be predicted by that measured using auditory-only (AO)
      testing, and (3) with visual cues, listeners with greater lipreading skills would
      perceive less DIR benefit than did listeners with lesser lipreading skills.
      DESIGN: Twenty-four adults with sensorineural hearing loss were recruited. Their
      speech recognition performances were measured in two hearing aid microphone modes
      (DIR and OMNI), at various signal-to-noise ratios (SNR, -10 to +10 dB in 4-dB
      steps) and under two presentation conditions (AV and AO) by using the AV version
      of the Connected Speech Test. Microphone preference (DIR versus OMNI) was also
      assessed with and without visual cues at each of the SNRs by using the same
      Connected Speech Test sentences. Lipreading skills were measured using the Utley
      test. RESULTS: The speech recognition data revealed that the participants
      obtained significantly less DIR benefit in the AV condition because their AV
      performances were at the ceiling level. Consistent with this, the likelihood of
      preferring DIR processing was significantly reduced when visual cues were
      available to the listeners. Further, DIR benefit measured in the AV condition was
      not correlated with that measured in the AO condition while being significantly
      and negatively correlated with lipreading skill. CONCLUSIONS: These results
      suggest that AO laboratory testing overestimates the DIR benefit and preference
      for DIR processing that hearing aid users may have in most face-to-face
      conversations in typical SNR, real-world environments. Additionally, because the
      DIR benefit measured in the AV condition cannot be predicted by the benefit score
      obtained from traditional AO laboratory testing, the effect of visual cues should
      be considered in establishing a valid laboratory/clinical environment and
      protocol for DIR microphone hearing aid testing. In light of these findings,
      consultations should be provided for hearing aid users with superior lipreading
      skills to help them adjust their expectations regarding the possibly small
      perceivable benefit gained from DIR microphone hearing aids.

PMID- 19864955
TI  - Is temperature an effect modifier of the association between green tea intake and
      gastric cancer risk?
AB  - We considered the relationship between green tea and gastric cancer risk in
      Harbin, Heilongjiang province, Northeast China, an area with high baseline risk
      of stomach cancer. We used data from a case-control study conducted from 1987 to
      1989 among 266 incident cases of stomach cancer and 533 controls admitted to the
      same hospitals as cases, with non-neoplastic and non-gastric diseases. No
      association emerged when tea consumption alone was considered: the odds ratio
      (OR) for green tea consumption was 0.87 (95% CI: 0.60-1.25) for green tea intake
      > or = 750 g/year versus no intake and 0.99 (95% CI: 0.97-1.02) for an increment
      of 500 g of tea per year. When tea consumption was classified according to the
      temperature, however, the OR was 0.19 (95% CI: 0.07-0.49) for lukewarm tea intake
      > or = 750 g/year and 1.27 (95% CI: 0.85-1.90) for hot tea intake (P value for
      interaction <0.001) as compared with non-drinkers. The corresponding ORs for an
      increment of 500 g of tea per year were 0.61 (95% CI: 0.45-0.82) and 1.03 (95%
      CI: 0.99-1.07) for lukewarm and hot tea, respectively (P value for interaction
      <0.001). We found an inverse relationship between green tea drinking and gastric
      cancer risk limited to the intake of lukewarm tea.

PMID- 19864956
TI  - Practice variation after implementation of a protocol for migraines in children.
AB  - The objective of this study was to evaluate the changes that occurred in the
      treatment of migraine over a 10-year period in a pediatric emergency department
      (ED) after the implementation of a protocol. The method employed was a
      comparative retrospective chart review of children diagnosed with migraine in an
      ED. The two study periods were 1996-1997, and 2006-2007. A protocol suggesting a
      specific approach was implemented in the ED in 1999. The primary outcome was the
      medications used in the ED. There were 182 visits for migraine in 2006-2007
      compared with 144 visits in 1996-1997. More patients were treated in the ED in
      2006-2007 compared with 1996-1997: 50 versus 30%, a difference of 20% (95%
      confidence interval: 9, 30). The treatments used were also different. In
      conclusion, a variation in the treatment of migraine was observed over a 10-year
      period in a pediatric ED after the implementation of a treatment protocol.

PMID- 19864957
TI  - Antiretroviral treatment initiation among HIV-infected pregnant women with low
      CD4(+) cell counts in Gaborone, Botswana.
AB  - BACKGROUND: Botswana has the most comprehensive public program in Africa for
      providing antiretroviral therapy to treat HIV and prevent mother-to-child
      transmission (PMTCT). Botswana guidelines prioritize CD4(+) cell count testing
      during pregnancy and initiation of highly active antiretroviral treatment (HAART)
      for women who qualify for treatment. We analyzed rates of HIV testing, CD4 cell
      count testing, and HAART initiation during pregnancy. METHODS: From October 2007
      through June 2008, we reviewed obstetric and laboratory records of women at
      Princess Marina Hospital in Gaborone, Botswana. RESULTS: We recorded information
      from 3056 women. Of 2675 women eligible for the PMTCT program, 2623 (98%) had a
      documented HIV status, of whom 793 (30%) were HIV infected. Among women who were
      treatment naive at pregnancy conception, 397 (59%) had recorded CD4(+) cell
      counts, of whom 62 (16%) had a CD4(+) cell count <200 cells per cubic millimeter.
      Among this subset, 23 (37%) initiated HAART during pregnancy, 26 (42%) received
      zidovudine prophylaxis, and 13 (21%) received no therapy. CONCLUSIONS: We
      observed low rates of CD4(+) cell count testing and HAART initiation during
      pregnancy. Antenatal clinics should prioritize CD4(+) cell count testing and
      referral of women who qualify for HAART to maximize benefits of maternal
      treatment and PMTCT.

PMID- 19864958
TI  - Perindopril-based blood pressure lowering reduces major vascular events in Asian
      and Western participants with cerebrovascular disease: the PROGRESS trial.
AB  - OBJECTIVE: To assess the benefits of blood pressure (BP) lowering on vascular
      events separately for Asian and for Western participants with particular emphasis
      on stroke subtypes and cardiac outcomes. METHODS: This is a subsidiary analysis
      of Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a
      randomized, placebo-controlled trial that established the benefits of BP lowering
      in 6105 patients with cerebrovascular disease, randomly assigned to either active
      treatment (perindopril for all, and indapamide for those with neither an
      indication for, nor a contraindication to, a diuretic) or placebo(s). Outcomes
      are total and cause-specific vascular outcomes. RESULTS: The annual rates for
      total major vascular events were 4.2% in Asian and 5.2% in Western participants.
      Overall stroke rates were greater in Asian compared to Western participants with
      proportionally more lacunar infarctions and haemorrhagic strokes in Asians and
      more cardio-embolic infarctions and large artery infarctions in Western
      participants. Active treatment reduced BP by 10.3/4.6 mmHg in Asian, and by
      8.1/3.6 mmHg in Western participants. Among Asian participants there was a 38%
      [95% confidence interval (CI) 23-49%] reduction in major vascular events compared
      to a 20% (95% CI 7-31%) reduction in Western participants (P homogeneity = 0.06).
      Similarly, there were higher relative risk reductions for all other outcomes
      among Asian participants, but this only reached statistical significance for
      heart failure and vascular death (P = 0.02 for each). The number needed to treat
      for major vascular events over 5 years was 15 (95% CI 10-26) in Asian compared to
      28 (95% CI 17-94) in Western participants (P homogeneity = 0.09). CONCLUSIONS: BP
      lowering reduces the risk of major vascular events, with separately significant
      reductions, in both Asia and the West.

PMID- 19864959
TI  - Potentiation by candesartan of protective effects of pioglitazone against type 2
      diabetic cardiovascular and renal complications in obese mice.
AB  - OBJECTIVES: The efficacy of renin-angiotensin system (RAS) blockers on type 2
      diabetes and its complications remains to be defined. This study was undertaken
      to test the hypothesis that candesartan may enhance the protective effects of
      pioglitazone against type 2 diabetes. METHODS: We compared the effects of
      pioglitazone, candesartan, and their combination on cardiorenal and vascular
      injury, diabetes, and tissue oxidative stress in obese and type 2 diabetic db/db
      mice, and also examined the effects of tempol, a superoxide dismutase (SOD)
      mimetic, on db/db mice to define the role of oxidative stress. RESULTS: The
      addition of candesartan to pioglitazone significantly potentiated the suppressive
      effects of pioglitazone on cardiac macrophage infiltration and interstitial
      fibrosis, and glomerular macrophage infiltration and sclerosis in db/db mice.
      These benefits of the combination of pioglitazone and candesartan in db/db mice
      were attributed to additive attenuation of cardiorenal oxidative stress, through
      the attenuation of NADPH oxidase or the restoration of Cu/Zn-SOD and EC-SOD. The
      combination of these drugs reversed vascular endothelial dysfunction in db/db
      mice more than either monotherapy, by causing more phosphorylation of eNOS.
      Candesartan slightly augmented the improvement of glucose tolerance by
      pioglitazone in db/db mice, and this additive effect was mediated by more
      attenuation of oxidative stress. CONCLUSIONS: Our work demonstrated that
      candesartan significantly potentiated the protective effects of pioglitazone
      against cardiorenal and vascular injury, and diabetes in obese type 2 diabetic
      mice. Thus, the combination of pioglitazone with candesartan is potentially a
      promising therapeutic strategy for type 2 diabetes.

PMID- 19864960
TI  - Caffeine elicits c-Fos expression in horizontal diagonal band cholinergic
      neurons.
AB  - Caffeine is a widely self-administered psychostimulant with purported
      neuroprotective and procognitive effects in rodent models of aging. The
      cholinergic basal forebrain is important for arousal and attention and is
      implicated in age-related cognitive decline. Accordingly, we determined the
      effects of caffeine on cholinergic neuron activation in the rat basal forebrain.
      Young adult (age 2 months) male rats were treated with caffeine (0, 10, or 50
      mg/kg) and killed 2 h later. Caffeine significantly increased c-Fos expression in
      cholinergic neurons of the horizontal limb of the diagonal band of Broca but not
      other basal forebrain regions such as the medial septum or substantia innominata.
      The horizontal limb of the diagonal band of Broca provides cholinergic
      innervation to the olfactory bulb, suggesting that deficits in this structure may
      contribute to diminished olfactory function observed in Alzheimer's disease
      patients. These results suggest that part of the cognitive-enhancing effects of
      caffeine may be mediated through activation of this part of the cholinergic basal
      forebrain.

PMID- 19864961
TI  - The face-sensitive N170 encodes social category information.
AB  - Prominent models of face perception posit that the encoding of social categories
      begins after initial structural encoding has completed. In contrast, we
      hypothesized that social category encoding may occur simultaneously with
      structural encoding. While event-related potentials were recorded, participants
      categorized the sex of sex-typical and sex-atypical faces. Results indicated that
      the face-sensitive right N170, a component involved in structural encoding, was
      larger for sex-typical relative to sex-atypical faces. Moreover, its amplitude
      predicted the efficiency of sex-category judgments. The right P1 component also
      peaked earlier for sex-typical faces. These findings show that social category
      encoding and the extraction of lower-level face information operate in parallel,
      suggesting that they may be accomplished by a single dynamic process rather than
      two separate mechanisms.

PMID- 19864962
TI  - Automobile windscreen rake, spectacle lenses, and effective transmittance.
AB  - PURPOSE: To investigate the effect of windscreen rake angle on effective
      transmittance and the contribution of spectacle lenses to the total transmittance
      of the system. METHODS: Theoretical analysis has been carried out using the
      Fresnel reflectance equations. RESULTS: Windscreen rake can reduce effective
      transmittance significantly at angles present on modern aerodynamic vehicles.
      Spectacle lenses reduce the total transmittance still further, often to below the
      minimum level permissible in current international standards for windscreens.
      CONCLUSIONS: Drivers should always be supplied antireflection-coated lenses where
      there is a chance of their spectacles being used for night-time driving, if
      current International standards for windscreen transmittance are to be met by the
      spectacle-windscreen combination. Windscreen rake angle should be accounted for
      both in the International Organization for Standardization transmittance
      standards and in roadside testing devices.

PMID- 19864964
TI  - Impact of rapid streptococcal test on antibiotic use in a pediatric emergency
      department.
AB  - Acute pharyngitis is commonly seen in children. Group A beta-hemolytic
      Streptococcus is the most common bacterial cause of acute pharyngitis and
      accounts for approximately 15% to 30% of cases in children, but this condition is
      generally overdiagnosed and overtreated. The availability of rapid streptococcal
      tests (RSTs) have made this diagnosis simpler and reduced the use of antibiotics.
      Overuse of antibiotics leads to drug-resistant bacterial strains. Reducing the
      number of antibiotic prescriptions provided for upper respiratory tract
      infections has been strongly recommended to limit bacterial resistance.
      OBJECTIVE: To assess the impact of RSTs on antibiotic prescriptions in children
      with pharyngitis in the emergency department. METHODS: A retrospective study from
      September 2005 to September 2007 of all patients (3-18 years old) presenting to
      the pediatric emergency department with sore throat as the chief complaint or
      suspected clinically to have acute pharyngitis and who had an RST performed.
      Patients with a negative RST result had a culture performed. The information of
      the patients with the diagnosis of pharyngitis was also collected in a 2-year
      control period before the availability of the test. Patients with a negative RST
      result had a culture performed. In addition, the antibiotic prescriptions for
      these patients were also recorded. RESULTS: A total of 8280 patients were
      included in the study. Throat culture results of 1723 patients were reviewed in
      the pre-RST phase. During the post-RST phase, 6557 children underwent RST. The
      RST results were positive in 1474 children (22.5%) and negative in 5083 patients
      (77.5%). Rapid strep testing was associated with a lower antibiotic prescription
      rate for children with pharyngitis (41.38% for those treated in the pre-RST phase
      versus 22.45% for those treated in the post-RST phase; P < 0.001). CONCLUSIONS:
      The availability of a RST could substantially reduce the unnecessary prescription
      of antibiotics. This study supports the screening of all children with
      pharyngitis by performing an RST to guide decision making for antibiotic
      administration. This strategy has a significant impact on reducing the antibiotic
      prescription rate to almost 50%. In addition, only 2 children (0.04%) had
      negative rapid antigen test results with cultures positive for Streptococcus.

PMID- 19864965
TI  - Gastrostomy tube-related complaints in the pediatric emergency department:
      identifying opportunities for improvement.
AB  - OBJECTIVE: To describe the pediatric emergency medicine management of patients
      who present with gastrostomy tube (G-tube)-related complaints and identify
      opportunities for improving care and preventing G-tube complications. METHODS:
      Retrospective cross-sectional descriptive study of patients (aged <18 years) who
      received care at an urban children's hospital (110 beds) emergency department
      (ED) for G-tube-related complaints. RESULTS: Over a 23-month period, there were
      181 ED patient visits by 77 patients for G-tube-related complaints. The mean
      number of visits per patient was 2.4. There were 159 (88%) G-tube and 22 (12%)
      gastrojejunostomy tube (GJ-tube) patient visits. The standard type of G-tube used
      at the study site ED was an adjustable-length tube. The most common complaint for
      G-tubes was dislodgement (99, 62%); and for GJ-tubes, malfunction (11, 50%).
      There were 119 patient visits (75%) needing G-tube replacement. Of these, 115
      (97%) were successfully replaced in the ED, 85 (74%) by the pediatric emergency
      medicine attending physician, and 30 (26%) by the pediatric surgery service. The
      method of securing or documenting the intragastric depth of the adjustable-length
      tubes was documented in 15 (10%) of the 157 patients who had G-tubes or foley
      catheters at the time of ED disposition. The most common major G-tube
      complication was gastric outlet obstruction (3), and the most common major GJ
      tube complication was aspiration pneumonia (3) secondary to gastric malposition
      (2) or dislodgement (1) of the GJ-tube. Only 9 patient visits (5%) resulted in
      hospitalization, and there were no deaths. CONCLUSIONS: Patients with G-tubes had
      approximately 1.25 mean ED visits per year for G-tube complaints. The most common
      G-tube complaint was dislodgement. Most dislodged G-tubes were replaced by ED
      physicians without the assistance of surgeons, but documentation of management
      and methods of securing the tubes was often incomplete. There were few major
      complications or hospitalizations. Treatment guidelines are presented that
      emphasize documentation of confirming G-tube location at the time of disposition
      from the ED.

PMID- 19864966
TI  - Patients' and caregivers' beliefs about depression screening and referral in the
      emergency department.
AB  - OBJECTIVES: To explore patients' and parents'/caregivers' beliefs about the
      acceptability of universal depression screening in the emergency department (ED)
      and their perceptions of the barriers and facilitators to a mental health
      referral following a positive screen. METHODS: We conducted semistructured
      interviews with 60 patients seeking care and 59 caregivers in the ED of an urban
      children's hospital. Interviews were audiotaped, transcribed, coded, and entered
      into N6 (version 6.0; QSR, Thousand Oaks, Calif) for coding and content analysis.
      RESULTS: Patients and caregivers supported the idea of depression screening in
      the ED, generally viewing screening as a reflection of care and concern.
      Respondents reported apprehension about stigma, privacy, and provider
      sensitivity. Introducing the screening concept early in the visit and as part of
      routine care was believed to reduce stigma. Respondents generally indicated that
      although they would likely follow through with a referral if given, stigma and
      denial were viewed as significant barriers. Caregivers also reported that
      logistical problems such as transportation, insurance, and agency hours created
      barriers to help seeking, but this could be offset by social supports and
      information about the agency and the provider. CONCLUSIONS: Patients and
      caregivers generally support depression screening in the pediatric ED but
      identified several barriers to screening and referral for treatment.
      Recommendations include introduction of universal screening early in the ED
      visit, provision of specific information about the meaning of screening results,
      and support from family and health care providers to help reduce stigma and
      increase referral acceptability.

PMID- 19864968
TI  - Ceftriaxone for refractory acute otitis media: impact of a clinical practice
      guideline.
AB  - OBJECTIVE: To determine the effect of a clinical practice guideline (CPG) on the
      use of ceftriaxone for the treatment of refractory acute otitis media (AOM) at a
      tertiary care pediatric hospital. METHODS: Charts of all patients aged 3 to 60
      months referred from an emergency department to a day treatment center for
      management of refractory AOM with ceftriaxone were reviewed. Data were collected
      during two 18-month periods before and after implementation of a CPG developed by
      a local group of experts. Ceftriaxone was indicated for children with symptomatic
      AOM despite 48 hours of treatment with high-dosage amoxicillin or amoxicillin
      clavulanate (>75 mg/kg per day) or despite receiving 1 of these 2 antibiotics
      over the previous month. Overall treatment was considered adequate if patients
      met these indications for ceftriaxone, if at least 3 daily doses had been
      prescribed, and if all doses were within the 40- to 60-mg/kg range. RESULTS:
      Thirty-two emergency physicians referred 127 patients to the day treatment center
      (60 preimplementation and 67 postimplementation of the CPG). The mean (SD)
      patient ages were 16.7 (7.4) and 19.7 (12.4) months in the preimplementation and
      postimplementation groups, respectively. Indications for prescription of
      ceftriaxone were adequate in 16.7% of the preguideline and 22.4% of the
      postguideline groups (P = 0.4). Physicians were twice as likely to use
      ceftriaxone adequately after the guideline's implementation, but this result was
      not statistically significant (crude odds ratio, 2.2; 95% confidence interval,
      0.5-9.0). CONCLUSIONS: Implementation of a CPG for the treatment of refractory
      AOM with ceftriaxone did not improve indications for its use.

PMID- 19864969
TI  - The effect of diagnosis-specific computerized discharge instructions on 72-hour
      return visits to the pediatric emergency department.
AB  - OBJECTIVE: The number of patients returning to the pediatric emergency department
      (PED) within 72 hours of discharge is frequently cited as a benchmark for quality
      patient care. The purpose of this study was to determine whether the introduction
      of diagnosis-specific computer-generated discharge instructions would decrease
      the number of medically unnecessary return visits to the PED. METHODS: A
      retrospective chart review of patients who returned to the PED within 72 hours of
      discharge was performed. Charts were reviewed from 2 comparable periods:
      September 2004 to February 2005, when handwritten discharge instructions were
      issued to each patient, and September 2005 to February 2006, when each patient
      received computer-generated diagnosis-specific discharge instructions. The
      patient's age, primary care provider, insurance status, chief complaint, vital
      signs, history, physical examination, plan of care, and diagnosis at each visit
      were recorded. Cases were excluded if the patient left against medical advice or
      without being seen, was admitted to the hospital on the first visit, or had
      incomplete or missing records. The medical necessity of the return visit was
      rated as "yes," "no," or "indeterminate" based on review of the visit noting
      reason for return, history and physical examination, diagnosis, and interventions
      or changes in the initial care plan. RESULTS: Of all return visits to the PED
      within 72 hours of discharge, 13% were deemed unnecessary for patients receiving
      handwritten instructions compared with 15% for patients receiving computer
      generated instructions (P = 0.5, not significant). For each additional year of
      age, the return visit was 1.07 times as likely to be medically appropriate (95%
      confidence interval, 1.03-1.12; P = 0.002). Patients who returned to the PED more
      than once were 2.69 times more likely to have a medically appropriate visit as
      were those with only 1 return visit (95% confidence interval, 0.95-7.58; P =
      0.062). CONCLUSIONS: Computer-generated diagnosis-specific discharge instructions
      do not decrease the number of medically unnecessary repeat visits to the PED.

PMID- 19864967
TI  - Epidemiology of psychiatric-related visits to emergency departments in a
      multicenter collaborative research pediatric network.
AB  - OBJECTIVES: Describe the epidemiology of pediatric psychiatric-related visits to
      emergency departments participating in the Pediatric Emergency Care Applied
      Research Network. METHODS: Retrospective analysis of emergency department
      presentations for psychiatric-related visits (International Classification of
      Diseases, Ninth Revision, codes 290.0-314.90) for years 2003 to 2005 at 24
      participating Pediatric Emergency Care Applied Research Network hospitals. All
      patients who had psychiatric-related emergency department visits aged 19 years or
      younger were eligible. Age, sex, race, ethnicity, insurance status, mode of
      arrival, length of stay, and disposition were described for psychiatric-related
      visits and compared with non-psychiatric-related visits. RESULTS: Pediatric
      psychiatric-related visits accounted for 3.3% of all participating emergency
      department visits (84,973/2,580,299). Patients with psychiatric-related visits
      were older (mean +/- SD age, 12.7 +/- 3.9 years vs. 5.9 +/- 5.6 years, P <
      0.001), had a higher rate ambulance arrival (19.4% vs 8.2%, P < 0.0001), had a
      longer median length of stay (3.2 vs 2.1 hours, P < 0.0001), and had a higher
      rate of admission (30.5% vs 11.2%, P < 0.0001) when compared with non-psychiatric
      related patient presentations. Older age, female sex, white race, ambulance
      arrival, and governmental insurance were factors independently associated with
      admission or transfer from the emergency department for psychiatric-related
      visits in multivariate regression analyses. CONCLUSIONS: Pediatric psychiatric
      related visits require more prehospital and emergency department resources and
      have higher admission/transfer rates than non-psychiatric-related visits within a
      large national pediatric emergency network.

PMID- 19864970
TI  - Presentation, evaluation, and treatment of clavicle fractures in preschool
      children presenting to an emergency department.
AB  - Clavicle fractures are a common injury among pediatric patients. Few data exist
      regarding specific etiologies and their management in the preadolescent patient.
      Our objective was to determine the specific source of injury and treatment
      techniques used in the youngest patient population. METHODS: Study Design. A
      multicenter retrospective chart review study. Setting. Twenty New Jersey and New
      York emergency departments from January, 2000 to February, 2007. Subjects.
      Consecutive patients younger than 2 years with the primary or secondary diagnosis
      of "clavicle fracture" according to the International Classification of Diseases,
      Ninth Revision. A manual chart review was performed for specific data points.
      RESULTS: Two hundred twenty-eight patients met the inclusion criteria. Complete
      charts were available for 189 patients: 0 to 6 months (n = 14), 6 to 12 months (n
      = 41), 12 to 18 months (n = 53), and 18 to 24 months (n = 81). Males comprised
      56% of the patients. The 3 most common etiologies of clavicle fractures were as
      follows: fall from bed/crib, 34%; playful activity, 17%; and fall not otherwise
      specified (NOS), 16%. Analgesic medications were reported in 32% of children
      while in the emergency department, and 51% were given a prescription on
      discharge. The most common immobilization technique was sling in 43% of patients.
      No immobilization was performed 37% of the time. Two patients (1%) were reported
      to the Division of Youth and Family Services. CONCLUSIONS: In the youngest
      patient population, falling from a crib or bed is the most common etiology of
      clavicle fractures. Treatment for these injuries was found to be highly variable.

PMID- 19864971
TI  - Early expression changes of complement regulatory proteins and C5A receptor
      (CD88) on leukocytes after multiple injury in humans.
AB  - As a crucial element of innate immunity, the complement cascade becomes activated
      after severe trauma. Regulation of the complement cascade and protection against
      complement-mediated tissue destruction is provided by a selection of soluble and
      membrane-bound complement regulatory proteins (CRegs). To date, the leukocyte
      expression profile of CRegs in multiple injured patients is unknown. In the
      present study, expression of CRegs and the C5a receptor (CD88) was analyzed on
      neutrophils, monocytes, and lymphocytes by flow cytometry. Whole blood samples
      were obtained from healthy volunteers (n = 16) or multiple injured patients (n =
      12) on admission in the emergency department and 4, 12, 24, 120, and 240 h after
      trauma. The content of CRegs and CD88 on leukocytes was significantly altered
      posttrauma: CD55 (decay accelerating factor) displayed a time-dependent, elevated
      expression pattern on neutrophils and monocytes, but not on lymphocytes. CD59
      (membrane attack complex inhibitor) expression was significantly increased on
      neutrophils and monocytes at the time of admission and after 5 to 10 days in
      lymphocytes. CD46 (membrane cofactor protein) was significantly down-regulated in
      all three cell types posttrauma. CD35 (complement receptor 1) expression on
      neutrophils was initially decreased, whereas monocytes presented a significant
      increase in CD35 expression. CD35 on lymphocyte remained unchanged throughout the
      observation period. CD88 expression was considerably reduced on leukocytes
      between 0 and 240 h after injury. CD59, CD46, and CD88 expression values on
      neutrophils reversely correlated with severity of injury. In summary, expression
      profiles of CRegs and CD88 on leukocytes are specifically altered after
      polytrauma in humans, indicating a trauma-induced "complementopathy."

PMID- 19864973
TI  - Clarithromycin resistance and efficacy of clarithromycin-containing triple
      eradication therapy for Helicobacter pylori infection in type 2 diabetes mellitus
      patients.
AB  - BACKGROUND: Antimicrobial resistance in Helicobacter pylori infection is an
      important factor leading to failure of therapy. The aim of this study was to
      determine the eradication rate of H pylori in type 2 diabetes mellitus and to
      assess the effect of clarithromycin resistance on H pylori eradication. METHOD:
      Fifty-six consecutive patients with type 2 diabetes mellitus and 58 age- and sex
      matched control patients were included in the study. H pylori infection was
      assessed by a rapid urease test and histopathological examination of biopsy
      specimens. Biopsies were also taken for antibiotic susceptibility testing. All
      enrolled patients were treated with triple therapy consisting of clarithromycin,
      amoxicillin, and pantoprazole for 14 days. C-13 urea breath test was performed 6
      weeks after completing the triple therapy to assess eradication and associated
      point mutations using real-time polymerase chain reaction (PCR). RESULTS: H
      pylori was eradicated in 42.9% of diabetic patients and 79.3% of control
      patients, (P < 0.05). In type 2 diabetes mellitus patients, clarithromycin
      resistance was 64.3% (36/56), while in the control group, clarithromycin
      resistance was 35.7% (20/58) (P < 0.05). H pylori was eradicated in 14 (70%) of
      the 20 clarithromycin-susceptible diabetic patients and in only 10 (27.8%) of the
      36 clarithromycin-resistant diabetic patients. CONCLUSION: The H pylori
      eradication rate was significantly lower and clarithromycin resistance was
      significantly higher in type 2 diabetics. Alternative and new treatment protocols
      and antibiotic susceptibility testing are needed to achieve successful
      eradication rates.

PMID- 19864974
TI  - Medication use for diabetes, hypertension, and hypercholesterolemia from 1988
      1994 to 2001-2006.
AB  - The objective of this study was to compare rates of use of medications for
      diabetes, hypertension, and hypercholesterolemia between 1988-1994 and 2001-2006
      and determine whether increased medication use may be partly attributable to
      nonadherence to healthy lifestyle habits. This study analyzed and compared data
      from two different time periods in the National Health and Nutrition Examination
      Survey (NHANES). Disease prevalence rates increased 23% (P < 0.01), and
      medication use increased 121% (P < 0.05) over the study's period. Diabetes
      medication use increased from 5.3% to 8.7%, antihypertension medication from
      23.0% to 32.4%, and cholesterol-lowering medication from 4.5% to 16.7% (all P <
      0.05). By race, diabetes medication use increased most among Hispanics (7.2% to
      13.2%), antihypertension use increased most among non-Hispanic blacks (30.8% and
      39.6%), and cholesterol medication increased most in non-Hispanic whites (4.9% to
      17.8%) (all P < 0.05). Greater adherence to healthy lifestyle habits was
      associated with less use of medication (P < 0.01). Medication use for diabetes,
      hypertension, and hypercholesterolemia has increased between 1988-1994 and 2001
      2006 and is greater in people with fewer healthy lifestyle habits.

PMID- 19864975
TI  - Remifentanil to facilitate high-resolution computed tomography imaging of the
      chest or magnetic resonance imaging in infants.
AB  - INTRODUCTION: High-resolution computed tomography (CT) imaging or magnetic
      resonance (MR) imaging may require brief periods of apnea for image acquisition.
      In adults, this may be done by voluntary breath holding. In infants and children,
      such studies are generally performed under general anesthesia using a laryngeal
      mask airway with maintenance of spontaneous ventilation. METHODS: We report a
      technique using the short-acting synthetic opioid, remifentanil, as part of an
      anesthetic technique to provide brief periods of apnea and the rapid resumption
      of spontaneous ventilation. RESULTS: The study cohort included 12 patients (8 for
      high-resolution CT imaging and 4 for abdominal MR imaging) who ranged in age from
      6 to 16 months. General anesthesia with spontaneous ventilation was induced with
      sevoflurane in air and oxygen. When apnea was required, remifentanil (3
      microg/kg) was administered. Apnea occurred within 30-60 seconds following the
      bolus dose of remifentanil (42 +/- 8 seconds). The duration of apnea varied from
      3 to 8 minutes (4.8 +/- 1.5 minutes). Following the administration of
      remifentanil, there was a decrease in heart rate (HR) from 127 +/- 7 to a low of
      108 +/- 9 beats per minute (P < 0.0001). Systolic blood pressure (sBP) decreased
      from 84 +/- 6 mm Hg to 78 +/- 5 mm Hg (P = 0.0071). One patient received a fluid
      bolus (10 mL/kg) for a sBP of 56 mm Hg. No other adverse effects were noted.
      CONCLUSIONS: This technique facilitated anesthetic care by allowing the use of a
      laryngeal mask airway (LMA) for both the radiologic imaging as well as
      bronchoscopy which was performed after the radiologic imaging. The use of a bolus
      dose of remifentanil provided a brief period of apnea for the acquisition of the
      radiologic images.

PMID- 19864976
TI  - Helicobacter pylori and gastric cancer: a marital risk?

PMID- 19864978
TI  - Impetigo herpetiformis: a rare dermatosis of pregnancy.

PMID- 19864977
TI  - Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.
AB  - OBJECTIVE: To review adverse cutaneous drug reactions induced by tumor necrosis
      factor alpha (TNF-alpha) antagonist therapy. METHODS: A literature search was
      performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid
      bibliography searches. All language clinical trial data, case reports, letters,
      and review articles identified from the data sources were used. RESULTS: Since
      the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug
      reactions has increased significantly. A wide range of different skin lesions
      might occur during TNF-alpha antagonist treatment. New onset or exacerbation of
      psoriasis has been reported in patients treated with TNF-alpha antagonists for a
      variety of rheumatologic conditions. TNF-alpha antagonist therapy has been
      associated with a lupus-like syndrome; most of these case reports occurred in
      patients receiving either etanercept or infliximab. Serious skin reactions such
      as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis
      have been reported rarely with the use of TNF-alpha antagonists. CONCLUSIONS: As
      the use of TNF-alpha antagonists continues to increase, the diagnosis and
      management of cutaneous side effects will become an increasingly important
      challenge. In patients receiving TNF-alpha antagonist treatment, skin disease
      should be considered, and clinicians need to be aware of the adverse reactions of
      these drugs.

PMID- 19864979
TI  - Polymyalgia rheumatica associated with neck surgery.

PMID- 19864980
TI  - Half and half nail secondary to chronic renal failure.

PMID- 19864981
TI  - Meningitis from an uncommon serotype of Streptococcus pneumoniae in a young
      child.

PMID- 19864982
TI  - Intracranial cryptococcal infection in an immunocompetent patient.

PMID- 19864983
TI  - Peripheral arterial disease: current perspectives and new trends in management.
AB  - Peripheral arterial disease (PAD) is defined as an arterial brachial index (ABI)
      of < or =0.90 in the lower extremities and results from a narrowing of the
      arteries as a result of progressive atherosclerosis. PAD affects 12-20% of
      Americans aged 65 years or older; however, most are asymptomatic and many do not
      seek treatment. Improved awareness and education in both the general population
      and among health care providers about these modifiable risk factors has the
      potential to improve general health and decrease morbidity and mortality
      secondary to atherosclerotic vascular disease.

PMID- 19864984
TI  - Uterine arterial pseudoaneurysm: transcatheter arterial embolization as a rare
      complication of Caesarean section.
AB  - We describe the case of a 22-year-old female who presented to the emergency
      department with vaginal bleeding after Caesarean section. A diagnosis of
      pseudoaneurysm of the uterine artery was established radiologically.
      Pseudoaneurysm of the uterine artery is an uncommon cause of delayed postpartum
      hemorrhage. This condition can be treated with embolization.

PMID- 19864985
TI  - H. pylori-associated gastric cancer in a husband-wife pair: a veritable family
      affair.
AB  - Family environment probably represents a high route of transmission for H.
      pylori, a bacterium associated with gastric cancer (GC). We report two cases of
      GC in a husband-wife pair of immigrants from Romania. The disease was first
      diagnosed in the wife, and three years later in her husband of 55 years. Both
      patients had active H. pylori-related inflammation. Household family members of
      GC patients could be infected with a shared H. pylori strain, putting them at
      risk for developing the disease. Therefore, it may be justified to identify and
      eradicate the H. pylori infection in such family members early, before the
      neoplastic changes become irreversible.

PMID- 19864986
TI  - Pharmacotherapy use versus a healthy lifestyle.

PMID- 19864987
TI  - Mycobacterium chelonae vertebral osteomyelitis.
AB  - Mycobacterium chelonae is a rapidly growing mycobacterium (RGM) in Runyon group
      IV. This group includes all other nontuberculous mycobacterium (NTM) except the
      mycobacterium tuberculosis complex. The most commonly infected organ by RGM is
      the lung, usually in immunosuppressed patients or those with underlying lung
      disease. Vertebral infection is very rare. Osteomyelitis is rarely caused by M.
      chelonae, and only one other case of M. chelonae vertebral osteomyelitis has been
      reported. A case of M. chelonae vertebral osteomyelitis in a man with intravenous
      drug abuse is reported, and NTM osteomyelitis is reviewed with a focus on M.
      chelonae and appropriate treatment options for M. chelonae vertebral
      osteomyelitis.

PMID- 19864988
TI  - Ankle brachial index measurement in primary care setting: how long does it take?
AB  - BACKGROUND: Peripheral arterial disease (PAD) affects over 8 million people in
      the United States and has been found to be associated with an increased incidence
      of coronary and carotid artery disease. The ankle brachial index (ABI)
      measurement is a highly specific noninvasive screening and diagnostic test for
      PAD, but is rarely performed in primary care office settings. This study sought
      to determine the actual performance time involved in completing an ABI in a
      primary care office. METHODS: Data were collected by one provider on a
      convenience sample of women who met the inclusion criteria. The time was recorded
      at the beginning and upon the completion of the ABI procedure for each patient.
      Analysis of the time data was completed and barriers to performing the ABI were
      recorded by the provider. RESULTS: The average time to complete an ABI was 5
      minutes, with a range of 3-11 minutes. In 83.8% of patient encounters, the ABI
      procedure took less than 6 minutes to complete. Barriers identified by the
      provider included the additional time needed to explain the test and assist
      patients into the proper testing position. CONCLUSIONS: The actual performance
      time for an ABI in a primary care setting takes an average of 5 minutes, but
      additional time may be required for patient preparation and education. With
      proper scheduling and training, the ABI can be completed in a timely manner. The
      ABI is an important screening/diagnostic test that can be performed in primary
      care and potentially impact patient treatment plans.

PMID- 19864989
TI  - Successful treatment of severe pneumocystis pneumonia with clindamycin-primaquine
      in an HIV-negative patient.
AB  - Pneumocystis pneumonia is an increasingly recognized threat in non-HIV
      immunosuppressed patients and is associated with worse outcomes compared to HIV
      infected patients. The preferred first line treatment is trimethoprim
      sulfamethoxazole; however, second line treatments for those intolerant of this
      regimen have been primarily studied in patients with acquired immunodeficiency
      syndrome (AIDS). We report a case of Pneumocystis pneumonia in a 75-year-old man
      with chronic lymphocytic leukemia (CLL) and a history of sulfa allergy
      successfully treated with clindamycin-primaquine.

PMID- 19864990
TI  - Electroconvulsive therapy for malignant catatonia in adolescence.
AB  - Malignant catatonia is a severe form of catatonia which is acute in onset, and is
      systemically devastating, as it is associated with fever and autonomic
      instability. Although rarely described in children and adolescents, malignant
      catatonia should feature prominently in the differential diagnosis of acute
      pediatric encephalopathies, as it is a treatable syndrome. The case of a 17-year
      old adolescent with sickle cell anemia is presented. The patient developed
      malignant catatonia and responded dramatically to electroconvulsive therapy.

PMID- 19864991
TI  - Postcholecystectomy colon cancer: an unanswered question.

PMID- 19864992
TI  - A previous cholecystectomy increases the risk of developing advanced adenomas of
      the colon.
AB  - BACKGROUND: There is limited data assessing the relationship between
      cholecystectomy and colorectal adenomatous polyps (AP). Our aim was to determine
      if cholecystectomy was associated with an increased prevalence of advanced AP in
      male veterans. METHODS: The relationship of whether prior cholecystectomy
      modified the natural history of AP was investigated in a retrospective study. The
      patients were divided into two groups: 1) those with AP and a history of
      cholecystectomy, and 2) those with AP, but without a history of cholecystectomy.
      Factors in each group associated with advanced AP were examined by univariate
      analysis (UA) and stepwise logistic regression analysis to determine independent
      predictors of aggressive clinical characteristics of polyps. Statistical
      significance was determined at a P < or = 0.05. RESULTS: We identified a total of
      1234 patients with AP (cases = 127, controls = 1107). The mean age of patients
      was 64.1 +/- 1.9 (standard deviation) years. By UA, those with a prior
      cholecystectomy had a greater mean number of AP (4.2 vs. 3.5; P = 0.04) and more
      advanced polyps (P = 0.037) than those without a cholecystectomy. By logistic
      regression, prior cholecystectomy was associated with more advanced AP (OR = 1.5
      [1.0-2.2]; P = 0.04). Patients who had a cholecystectomy were 51% more likely to
      have advanced AP. There appeared to be a trend towards increased time from
      cholecystectomy being associated with advanced polyps (9.69 years vs. 8.99 years,
      P = 0.056). CONCLUSIONS: A prior cholecystectomy was independently associated
      with an increased risk of developing advanced AP. Also, there appeared to be a
      trend toward a greater prevalence of advanced lesions as postcholecystectomy time
      increased.

PMID- 19864993
TI  - Peripheral arterial disease: increasing awareness--a major step forward.

PMID- 19864994
TI  - Measuring our outcomes.

PMID- 19864996
TI  - An uncommon case of heart failure.
AB  - A 55-year-old man evaluated for syncope had mild and gradually progressive left
      ventricular systolic dysfunction on initial workup. Although not identified
      initially, repeat cardiac magnetic resonance one year later demonstrated the
      presence of trabeculations in the left ventricle consistent with the diagnosis of
      isolated non-compaction of the left ventricular myocardium. This case highlights
      the need for increased awareness of this entity among primary care physicians,
      cardiologists, and radiologists in order to enhance its identification. This case
      also demonstrates the advantages of cardiac magnetic resonance for diagnosis and
      provides insight into this rare type of cardiomyopathy in adults.

PMID- 19864995
TI  - Acute respiratory distress syndrome, sepsis, and cognitive decline: a review and
      case study.
AB  - The objective of this investigation is to review existing research pertaining to
      cognitive impairment and decline following critical illness and describe a case
      involving a 49-year-old female with sepsis and acute respiratory distress
      syndrome (ARDS) with no prior neurologic history who, compared to baseline
      neuropsychological test data, experienced dramatic cognitive decline and brain
      atrophy following treatment in the medical intensive care unit (ICU) at
      Vanderbilt University Medical Center. The patient participated in detailed
      clinical interviews and underwent comprehensive neuropsychological testing and
      neurological magnetic resonance imaging (MRI) at approximately 8 months and 3.5
      years after ICU discharge. Compared to pre-ICU baseline test data, her
      intellectual function declined approximately 2 standard deviations from 139 to
      106 (from the 99 to the 61 percentile) on a standardized intelligence test 8
      months post-discharge, with little subsequent improvement. Initial diffusion
      tensor brain magnetic resonance imaging (DT-MRI) at the end of ICU
      hospitalization showed diffuse abnormal hyperintense areas involving
      predominately white matter in both hemispheres and the left cerebellum. A brain
      MRI nearly 4 years after ICU discharge demonstrated interval development of
      profound and generalized atrophy with sulcal widening and ventricular
      enlargement. The magnitude of cognitive decline experienced by ICU survivors is
      difficult to quantify due to the unavailability of pre-morbid neuropsychological
      data. The current case, conducted on a patient with baseline neuropsychological
      data, illustrates the trajectory of decline occurring after critical illness and
      ICU-associated brain injury with marked atrophy and concomitant cognitive
      impairments.

PMID- 19864997
TI  - Diagnosis and treatment of the primary malignant meningioma in mediastinum: a
      case report.
AB  - Primary ectopic meningioma is rare and usually limited to the head and neck
      region. Until now its occurrence in the mediastinum has not been reported in the
      literature searched on Medline using the keywords meningioma and mediastinum. We
      report here a case of primary mediastinal malignant meningioma which was treated
      by surgical resection and additionally followed by radiotherapy. The clinical
      features, treatment, pathological findings, and prognosis are analyzed and the
      literature based on ectopic meningioma is reviewed.

PMID- 19864998
TI  - Collateral meridian acupressure therapy effectively relieves postregional
      anesthesia/analgesia backache.
AB  - Epidural and spinal aesthesia may cause backache. In fact, the overall incidence
      of postneuraxial block backache is 9% to 50% and the incidence of back pain on
      the third postoperative day ranges from 5.91% to 22% after spinal anesthesia.
      Five patients suffering from postneuraxial block backache after regional
      anesthesia or analgesia are reported. Despite administering conventional
      treatment modalities including bed rest, cold/warm packing, physical therapy, and
      medications with nonsteroidal anti-inflammatory drugs (NSAIDs), strong
      analgesics, and opioids, the backache persisted and disturbed the patients' daily
      life. Surprisingly, utilization of a new acupressure technique, collateral
      meridian acupressure therapy (CMAT), relieved the backache dramatically.

PMID- 19864999
TI  - A rare cause of complicated hypertension: urinary bladder paraganglioma.
AB  - After a subarachnoid hemorrhage, a 35-year-old patient developed paroxystic
      hypertension accompanied by typical symptoms. These symptoms occurred exclusively
      after urination. A urinary bladder paraganglioma was discovered using iodine-123
      metaiodobenzylguanidine (I-123 MIBG) scintigraphy and magnetic resonance imaging
      (MRI) after the detection of an abnormally elevated plasma metanephrine
      measurement. A partial cystectomy was performed which cured the symptoms.
      Paragangliomas, defined by their extra-adrenal localization, have slightly
      different characteristics than pheochromocytomas, leading to specific care and
      follow up.

PMID- 19865000
TI  - Validation of an electrospray ionization LC-MS/MS method for quantitative
      analysis of raltegravir, etravirine, and 9 other antiretroviral agents in human
      plasma samples.
AB  - BACKGROUND: Raltegravir is the first human immunodeficiency virus-1 (HIV-1)
      integrase inhibitor used in treatment-experienced patients who have evidence of
      viral replication and HIV-1 strains resistance to multiple antiretroviral
      regimens. Etravirine is a novel NNRTI, active against HIV-1 strains harboring
      multiple NNRTI mutations. A liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method was developed for the quantification of raltegravir, etravirine,
      and 9 other antiretroviral agents (amprenavir, atazanavir, darunavir, efavirenz,
      indinavir, lopinavir, ritonavir, saquinavir, and tipranavir) in plasma at the
      concentrations associated with therapy. MATERIALS AND METHODS: The ritonavir
      analog, methyl indinavir, and lopinavir-d8 were used as internal standards, added
      to 100 microL of plasma sample prior to a protein precipitation using methanol.
      Chromatographic separation was achieved on a C18 HPLC column (Waters Sunfire 100
      x 2.1 mm, 3.5 microm) with a mobile phase gradient at a flow rate of 0.3 mL/min.
      Five microL of sample were injected into the LC-MS/MS system (Waters Quattro
      Premier XE) to determine concentrations of raltegravir, etravirine, and other
      antiretroviral agents. RESULTS AND DISCUSSION: This method showed an excellent
      linearity for all calibration curves (r2 > 0.998). The lower limit of
      quantification was established at 5 ng/mL for raltegravir and 40 ng/mL for
      etravirine, with precision and accuracy within +/-20% and 80% to 120% for all
      analytes. Intraassay and interassay precision and inaccuracy ranged from -9.2% to
      6.9% for raltegravir and from -14.3% to 12.3% for etravirine and were less than
      15% for all other compounds. No matrix effect was observed for any of the
      antiretrovirals studied. CONCLUSION: A rapid, specific, and sensitive LC-MS/MS
      method for quantification of raltegravir, etravirine, and 9 other antiretrovirals
      in human plasma was developed and was successfully applied for routine
      therapeutic drug monitoring.

PMID- 19865001
TI  - Simultaneous quantification of erlotinib, gefitinib, and imatinib in human plasma
      by liquid chromatography tandem mass spectrometry.
AB  - A quantitative liquid chromatography (LC)-mass spectrometry (MS)/MS method in
      human plasma was developed and validated for the tyrosine kinase inhibitors
      erlotinib, gefitinib, and imatinib in human plasma. Pre-treatment of the samples
      was achieved by using liquid-liquid extraction using D-8 imatinib as internal
      standard. Separation was performed on a Waters Alliance 2795 LC system using an
      XBridge RP18 column. The mass spectrometer Micromass was equipped with an electro
      spray ionization probe, operating in the positive mode. The calibration curves in
      plasma were linear for erlotinib, gefitinib, and imatinib over the concentration
      range of 5 to 3,000; 5 to 3,000, and 5 to 5,000 ng/mL, respectively. The intraday
      and interday accuracy ranged from 90% to 110% and the intraday and interday
      precision of the method was within 5%. The reported method provided the necessary
      linearity, precision, and accuracy to determine tyrosine kinase inhibitors in
      clinical research and for therapeutic drug monitoring.

PMID- 19865002
TI  - Effect of valproate on olanzapine plasma concentrations in patients with bipolar
      or schizoaffective disorder.
AB  - The effect of valproate on the steady-state plasma concentrations of olanzapine
      was investigated in 18 patients with bipolar or schizoaffective disorder.
      Additional valproate, at a dose ranging from 600 to 2000 mg/d, was administered
      for 4 weeks to patients stabilized on olanzapine (5-20 mg/d). During valproate
      coadministration, mean plasma olanzapine concentrations decreased significantly
      from 32.9 +/- 9.7 ng/mL at baseline to 27.4 +/- 9.8 ng/mL at week 2 (P = 0.02),
      and to 26.9 +/- 9.2 ng/mL at week 4 (P = 0.001). Smoking also decreased plasma
      olanzapine concentrations. Valproate coadministration with olanzapine was well
      tolerated and no patient showed a worsening of his or her psychopathological
      condition. These findings indicate that valproate, at doses of up to 2000 mg/d,
      is associated with a minimal, presumably not clinically significant, decrease in
      plasma olanzapine concentrations, possibly as a result of induction of olanzapine
      metabolism. New studies are needed to confirm that valproate could have mild
      inductive effects.

PMID- 19865003
TI  - Defining a lowest observable adverse effect hair concentrations of mercury for
      neurodevelopmental effects of prenatal methylmercury exposure through maternal
      fish consumption: a systematic review.
AB  - BACKGROUND: Methylmercury is an environmental pollutant that can cause
      irreversible effects on the development of children. Although there is no doubt
      that high exposure can cause neurodevelopmental deficits, the threshold that will
      adversely affect the developing fetus is not well defined. Our objective was to
      systematically review the evidence of neurodevelopmental risks of methylmercury
      to the unborn child from maternal fish consumption to define the lowest
      observable adverse effect hair concentration (LOAEHC). METHODS: A systematic
      review was conducted of all original research reporting on the effects of
      methylmercury on the human fetus. A literature search was undertaken using
      SCOPUS, Medline-Ovid, PubMed, Google Scholar, and EMBASE. Papers were selected
      based on the following inclusion criteria: 1) child neurodevelopmental outcome;
      2) comparison groups; and 3) methylmercury exposure through fish consumption.
      RESULTS: Forty-eight publications met these inclusion criteria. Thirty articles
      reported on longitudinal studies and 18 were cross-sectional studies. Variations
      in study design precluded formal meta-analysis. Based on an evaluation of these
      studies, we defined the LOAEHC at 0.3 microg/g of maternal hair mercury. The
      longitudinal studies yielded a LOAEHC of 0.5 microg/g. CONCLUSION: In the
      clinical context, the majority of pregnant women consume mercury-containing fish
      in amounts that are lower than the LOAEHC defined in this study. However, the
      LOAEHC is in the same order of magnitude of mercury exposure that occurs in
      significant numbers of women. Hence, although it appears safe to suggest that
      eating the recommended types and amounts of fish poses no measurable risks for
      neurodevelopmental deficits, analysis of hair mercury content before pregnancy
      might be suggested because dietary modification can decrease body content and
      risk.

PMID- 19865004
TI  - Surviving critical illness: acute respiratory distress syndrome as experienced by
      patients and their caregivers.
AB  - OBJECTIVE: To characterize the effects of critical illness in the daily lives and
      functioning of acute respiratory distress syndrome survivors. Survivors of acute
      respiratory distress syndrome, a systemic critical illness, often report poor
      quality of life based on responses to standardized questionnaires. However, the
      experiences of acute respiratory distress syndrome survivors have not been
      reported. DESIGN: We conducted semistructured interviews with 23 acute
      respiratory distress syndrome survivors and 24 caregivers 3 to 9 mos after
      intensive care unit admission, stopping enrollment after thematic saturation was
      reached. Transcripts were analyzed, using Colaizzi's qualitative methodology, to
      identify significant ways in which survivors' critical illness experience
      impacted their lives. SETTING: Medical and surgical intensive care units of an
      academic medical center and a community hospital. PATIENTS: We recruited
      consecutively 31 acute respiratory distress syndrome survivors and their informal
      caregivers. Eight patients died before completing interviews. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Participants related five key elements of
      experience as survivors of acute respiratory distress syndrome: 1) pervasive
      memories of critical care; 2) day-to-day impact of new disability; 3) critical
      illness defining the sense of self; 4) relationship strain and change; and 5)
      ability to cope with disability. Survivors described remarkable disability that
      persisted for months. Caregivers' interviews revealed substantial strain from
      caregiving responsibilities as well as frequent symptom minimization by patients.
      CONCLUSIONS: The diverse and unique experiences of acute respiratory distress
      syndrome survivors reflect the global impact of severe critical illness. We have
      identified symptom domains important to acute respiratory distress syndrome
      patients who are not well represented in existing health outcomes measures. These
      insights may aid the development of targeted interventions to enhance recovery
      and return of function after acute respiratory distress syndrome.

PMID- 19865006
TI  - Effect of acute inflammatory brain injury on accumulation of morphine and
      morphine 3- and 6-glucuronide in the human brain.
AB  - OBJECTIVE: In animals, central nervous system inflammation increases drug
      accumulation in the brain partly due to a loss of central nervous system drug
      efflux transporter function at the blood-brain barrier. To determine whether a
      similar loss of active drug efflux occurs in humans after acute inflammatory
      brain injury. DESIGN: Observational human pharmacokinetic study. SETTING: Medical
      surgical-neurosurgical intensive care unit at a university-affiliated, Canadian
      tertiary care center. PATIENTS: Patients with acute inflammatory brain injury,
      including subarachnoid hemorrhage (n = 10), intracerebral and/or intraventricular
      hemorrhage (n = 4), or closed head trauma (n = 2) who received morphine
      intravenously after being fitted with cerebrospinal fluid ventriculostomy and
      peripheral arterial catheters. INTERVENTIONS: We correlated the cerebrospinal
      fluid distribution of morphine, morphine-3-glucuronide, and morphine-6
      glucuronide with the cerebrospinal fluid and plasma concentration of the
      proinflammatory cytokine interleukin-6 and the passive marker of blood-brain
      barrier permeability, albumin. MEASUREMENTS AND MAIN RESULTS: Acute brain injury
      produced a robust inflammatory response in the central nervous system as
      reflected by the elevated concentration of interleukin-6 in cerebrospinal fluid.
      Penetration of morphine metabolites into the central nervous system increased in
      proportion to the neuroinflammatory response as demonstrated by the positive
      correlation between cerebrospinal fluid interleukin-6 exposure and the area under
      the curve cerebrospinal fluid/plasma ratio for morphine-3-glucuronide (r = .49, p
      < .001) and morphine-6-glucuronide (r = .51, p < .001). In contrast, distribution
      of morphine into the brain was not linked with cerebrospinal fluid interleukin-6
      exposure (r = .073, p = .54). Albumin concentrations in plasma and cerebrospinal
      fluid were consistently in the normal range, indicating that the physical
      integrity of the blood-brain barrier was likely undisturbed. CONCLUSIONS: Our
      results suggest that central nervous system inflammation following acute brain
      injury may selectively inhibit the activity of specific drug efflux transporters
      within the blood-brain barrier. This finding may have significant implications
      for patients with neuroinflammatory conditions when administered centrally acting
      drugs normally excluded from the brain by such transporters.

PMID- 19865007
TI  - Increasing power in randomized controlled trials.

PMID- 19865008
TI  - Point-of-care glucose testing in critically ill patients: visual logistics and a
      glycemic variability hypothesis.

PMID- 19865009
TI  - Two decades of simulation-based training: have we made progress?

PMID- 19865010
TI  - Ventilator-associated pneumonia and mortality: the controversy continues.

PMID- 19865011
TI  - Pulmonary artery catheter redux: physical findings in acute respiratory distress
      syndrome/acute lung injury.

PMID- 19865012
TI  - Consequences of ventilator asynchrony: why can't we all get along?

PMID- 19865013
TI  - HLA-DR monitoring in the intensive care unit--more than a tool for the scientist
      in the laboratory?

PMID- 19865014
TI  - Did we learn anything from Humpty Dumpty?

PMID- 19865015
TI  - Is it time for intensivists to learn genomics?

PMID- 19865016
TI  - No brain, no pain: does the injured brain stack up opioids?

PMID- 19865017
TI  - Aminoglycosides--engineering important patient-centered outcomes with
      antibiotics.

PMID- 19865018
TI  - Could insulin sensitization be used as an alternative to intensive insulin
      therapy to improve the survival of intensive care unit patients with stress
      induced hyperglycemia?

PMID- 19865019
TI  - Lactate: finally ready for prime time?

PMID- 19865021
TI  - Entodoxin tolerance in humans in vivo.

PMID- 19865023
TI  - Physician-assisted suicide.

PMID- 19865025
TI  - Acute left ventricular dilation and septic shock-induced myocardial dysfunction.

PMID- 19865026
TI  - Is it "lipid sink," hemodilution, or both?

PMID- 19865028
TI  - Neutrophil gelatinase-associated lipocalin in the intensive care unit: time to
      look beyond a single, threshold-based measurement?

PMID- 19865029
TI  - On extending the indications for the use of therapeutic hypothermia.

PMID- 19865031
TI  - Cryptococcal immune reconstitution inflammatory syndrome presenting with erosive
      bone lesions, arthritis and subcutaneous abscesses.

PMID- 19865032
TI  - Regarding inconsistent prevention of mother-to-child transmission of HIV
      guidelines: is WHO a victim or villain?

PMID- 19865033
TI  - Substituting nevirapine for efavirenz: risk factors for toxicity in nonnaive
      patients in a resource-constrained setting.

PMID- 19865034
TI  - SALT triage drill.

PMID- 19865035
TI  - From the editor-in-chief.

PMID- 19865036
TI  - Call centers, disaster medicine, and public health preparedness.

PMID- 19865037
TI  - Responding to gender-based violence in disasters.

PMID- 19865038
TI  - Disaster 101: a novel approach to health care students' disaster medicine and
      emergency preparedness training.

PMID- 19865039
TI  - War zones across the Middle East, Asia, and Africa: where are they now?

PMID- 19865040
TI  - Impact of Hurricane Ike on Texas poison center calls.
AB  - On September 13, 2008, Hurricane Ike made landfall in Texas, resulting in the
      mandatory evacuation of 8 counties before landfall and the declaration of
      disaster areas in 29 counties afterward. This study evaluated whether Hurricane
      Ike affected the pattern of Texas poison center calls. Texas poison center calls
      received from the disaster area counties were identified for 3 time periods:
      August 12 to September 10, 2008 (preevacuation), September 11 to 13, 2008
      (evacuation and hurricane landfall), and September 14 to 30, 2008
      (postevacuation). For selected types of calls, the mean daily call volume during
      time periods 2 and 3 was compared with a baseline range (BR) derived from the
      mean daily call volume during time period 1. During the evacuation and landfall
      period, gasoline exposure calls were higher than expected (mean 3, BR -1 to 2).
      During the postevacuation period, higher than expected numbers of calls were
      observed for gasoline exposures (mean 5, BR -1 to 2) and carbon monoxide
      exposures (mean 3, BR -1-1). During an evacuation, certain calls such as those
      involving gasoline exposures may increase. After a hurricane, calls such as those
      involving carbon monoxide and gasoline exposures may increase.

PMID- 19865041
TI  - Assessment of carbon monoxide exposure during the operation of indoor drive
      through mass vaccination clinics.
AB  - BACKGROUND: Drive-through mass vaccination clinics are an increasingly popular
      component of public health emergency response plans. One potential disadvantage,
      however, is the exposure of clinicians, volunteers, public health responders, and
      the public to carbon monoxide (CO) from vehicle exhaust emissions when clinics
      are held within garages or other enclosed structures. METHODS: CO levels were
      monitored during indoor drive-through clinics held on the same day at 2 separate
      locations in a rural upstate New York county. Each clinic was operated for 2
      hours during which seasonal influenza vaccines were administered to county
      residents as they remained within their vehicles. At each location, vehicle
      engines remained operating indoors within multiple lanes of traffic. No
      mechanical ventilation was used, but wind speeds through the buildings were
      relatively strong and consistent. CO was measured at breathing-zone height
      throughout the clinic sessions using direct-reading instruments. RESULTS: CO
      levels remained below detection for the majority of the clinic sessions. Short
      term, high CO exposures, however, were found to be associated with a small number
      of individual vehicles that were in apparent disrepair. CONCLUSIONS: The findings
      from this study indicate that CO exposures may be minimized by identifying and
      separately processing problematic vehicles before they enter the clinic. Direct
      reading CO monitors can help to identify these vehicles.

PMID- 19865042
TI  - Providing continuity of care for chronic diseases in the aftermath of Katrina:
      from field experience to policy recommendations.
AB  - This study sought to elicit challenges and solutions in the provision of health
      care to those with chronic diseases after Hurricane Katrina in coastal Alabama
      and Mississippi. In-depth interviews with 30 health and social service providers
      (key informants) and 4 focus groups with patients with chronic diseases were
      conducted. Subsequently an advisory panel of key informants was convened.
      Findings were summarized and key informants submitted additional feedback. The
      chronic diseases identified as medical management priorities by key informants
      were mental health, diabetes mellitus, hypertension, respiratory illness, end
      stage renal disease, cardiovascular disease, and cancer. The most frequently
      mentioned barrier to providing care was maintaining continuity of medications.
      Contributing factors were inadequate information (inaccessible medical records,
      poor patient knowledge) and financial constraints. Implemented or suggested
      solutions included relaxation of insurance limitations preventing advance
      prescription refills; better predisaster patient education to improve medical
      knowledge; promotion of personal health records; support for information
      technology systems at community health centers, in particular electronic medical
      records; improved allocation of donated medications/medical supplies (centralized
      coordination, decentralized distribution); and networking between local
      responders and external aid.

PMID- 19865043
TI  - Institute of Medicine's Forum on Medical and Public Health Preparedness for
      Catastrophic Events: activities and goals.

PMID- 19865047
TI  - The influence of age, bone quality and body mass index on periprosthetic femoral
      fractures: a biomechanical laboratory study.
AB  - BACKGROUND: A periprosthetic femoral fracture after total hip arthroplasty is a
      serious but uncommon complication, and therefore difficult to analyze clinically
      in scientifically and statistically valid study samples. With the aim of
      preventing these fractures the purpose of this study was to investigate potential
      risk factors associated with cementless hip arthroplasty in a standardized
      laboratory setup. Additionally, we aimed to clarify if the treatment with a
      cementless hip stem is fraught with higher risk of periprosthetic fracture for
      older patients compared to younger patients. MATERIAL/METHODS: A biomechanical
      setup was developed to provide analysis on sixteen femoral specimens of different
      age. A cementless hip stem was implanted into the specimens and loads -
      representing hip contact forces - were applied under standardized conditions
      until fracture occurred. The femurs were divided into two age groups (<70 and
      >or=77 years of age). RESULTS: The elderly specimens fractured at significantly
      lower maximum forces (<70: Fmax=5,308N; >or=77: Fmax=2,519N; p<0.01). Maximum
      fracture loads were found to correlate strongly with age (p=0.01), BMD (e.g. for
      the Ward's triangle: p<0.01) and BMI (p=0.04). CONCLUSIONS: In patients with
      advanced age treated with cementless hip stems the risk of suffering a
      periprosthetic fracture is significantly higher. It increases in patients with an
      age of 80 years or older, a Ward's triangle BMD below 0.500 g/cm2 and a BMI >33
      kg/m2. Whereas one single factor must not be viewed as an exclusion criterion for
      a cementless hip stem treatment, cumulation of these factors should alert the
      orthopaedic surgeon.

PMID- 19865048
TI  - Prognostic significance of immunohistochemical Rac1 expression in survival in
      early operable non-small cell lung cancer.
AB  - BACKGROUND: The small GTPases are involved in the regulation of critical cellular
      functions, such as transcription control, cell cycle, and organization of actin
      cytoskeleton. Although a number of investigations have established the
      significance of Rho-family GTPases in several human tumors, there is still little
      information available on the clinical significance of Rac1 expression in non
      small cell lung cancer (NSCLC). Therefore, immunohistologic expression of Rac1
      was studied in a tissue microarray of 111 Stage I-II NSCLCs and correlated with
      clinicopathologic parameters and clinical outcome. MATERIAL/METHODS: For this
      retrospective study 111 tissue samples, obtained from anonymized patients with
      early operable NSCLC (stage I-II), were used to construct a tissue microarray for
      immunohistochemical study. RESULTS: Rac1 showed a cytoplasmic pattern of
      expression in tumor cells, while normal lung components showed negative or weak
      cytoplasmic staining. Rac1 expression increased significantly with the
      advancement of the T stage (P<0.01) and the TNM stage (P<0.05). Analysis of
      overall survival showed that Rac1 expression was related to poor outcome
      (P=0.012), even in the group of stage I patients (P=0.023). Multivariate analysis
      showed that Rac1 overexpression was an independent marker for overall survival
      after adjusting for other prognostic factors (P=0.023). CONCLUSIONS: We found a
      positive prognostic value of immunohistologically determined Rac1 protein
      expression and presents Rac1 as a potential unfavorable prognosis biomarker in
      patients with early operable NSCLC.

PMID- 19865049
TI  - Outcome of in-vitro fertilization treatment and DDT levels in serum and
      follicular fluid.
AB  - BACKGROUND: Although p,p'-dichlorodiphenyltrichloroethane (DDT) is banned for
      agricultural purpose in Saudi Arabia, it is occasionally used to control vector
      borne diseases in certain regions of the country. MATERIAL/METHODS: A case
      control study was designed to investigate the possible effects of DDT and its
      metabolites on pregnancy and fertilization rate outcome. The study population was
      composed of 619 Saudi women (age 19-50 years) who sought in-vitro fertilization
      (IVF) treatment between 2002 and 2003. RESULTS: p,p'-DDE, the main metabolite of
      DDT, was the most frequently detected residue in serum or follicular fluid, with
      mean values of 1.646 microg/L and 0.407 microg/L, respectively. After controlling
      for many potential confounding variables, multiple logistic regression analysis
      revealed no association between pregnancy outcome or fertilization rate and p,p'
      DDE levels in serum or follicular fluid. CONCLUSIONS: The inability to identify
      an effect may be related to the comparatively low concentrations of DDE in our
      population. But because p,p'-DDE was detected in the serum of 77.7% our
      participants, it should be considered as a matter of public heath concern.
      Currently there is no active source of DDT in our region; therefore, further
      studies are needed to identify sources in order to develop preventive measures
      because we can not exclude its potential reproductive toxicity.

PMID- 19865050
TI  - Influence of selected angiotensin-converting enzyme inhibitors on alloxan-induced
      diabetic cataract in rabbits.
AB  - BACKGROUND: Hyperglycemia enhances cataractogenesis. Elevated glucose level is
      commonly accompanied by arterial hypertension, for which angiotensin-converting
      enzyme (ACE) inhibitors (ACEIs) are a widely used intervention. ACE inhibitors
      exert some endothelial pleiotropic actions and can beneficially modulate glucose
      control and some other metabolic pathways. The purpose of this study was to
      evaluate the effect of ACEIs on cataract formation in experimental alloxan
      induced diabetes in rabbits and assess the role of the reactive function group of
      the ACEIs in this process. MATERIAL/METHODS: Two study and two control groups of
      rabbits were examined. In the study groups and in one of the control groups,
      diabetes was induced by alloxan. The study groups were assigned to receive
      captopril or enalapril for six months; the controls received distilled water.
      Glucose concentration was monitored with a glucometer. A biomicroscope and an
      ophthalmoscope were used to evaluate lens opacity and cataractogenesis. RESULTS:
      Six-month administration of ACEI to rabbis resulted in a delay of diabetic
      cataractogenesis. The rate of cataract formation was significantly lower in the
      group treated with captopril than in the enalapril group. A difference in
      morphology of lens opacity formation between the two study groups was observed.
      CONCLUSIONS: ACEIs delay diabetic cataractogenesis in an experimental animal
      model. The ACEI functional groups have different influences on the pattern and
      rate of lens opacity.

PMID- 19865051
TI  - The effect of memantine and levodopa/carbidopa on the responses of phrenic nerve
      diaphragm preparations from aged rats.
AB  - BACKGROUND: Alzheimer's dementia (AD) and Parkinsonism are common in geriatric
      patients. Skeletal muscles are important for proper function of aging animals and
      humans. This study focuses on the influence of memantine (used in moderate to
      severe AD) and levodopa/carbidopa (LD/CD) (a cornerstone of Parkinson's disease
      treatment) on responses of isolated phrenic nerve-diaphragms (IPNDs) of aged male
      rats. MATERIAL/METHODS: Of 100 aged male albino rats, 20 were untreated to study
      the in vitro effects of memantine and LD/CD on IPNDs and 80 were divided into
      groups 1 (control), 2 (oral memantine, 1.5 mg/kg/d), 3 (twice daily
      intraperitoneal LD/CD, 25/2.5 mg/kg), and 4 (both drugs). After three weeks
      treatment the animals were sacrificed. Ten rats from each group were used to
      harvest IPNDs to study the effect of gallamine and 10 rats to measure nAchR
      (nicotinic acetylcholine receptor) alpha subunit mRNA by PCR. RESULTS: The
      heights of indirectly elicited contractions were 63.1+/-4.6, 41.5+/-4.5, 70.6+/
      4.7, and 53.9+/-3.3 mm for groups 1-4, respectively, and all differences were
      statistically significant (p<0.05). Memantine caused a leftward shift of the
      gallamine concentration-response curve and LD/CD a rightward shift. Reversal of
      neuromuscular block required larger neostigmine concentrations in the memantine
      group and smaller concentrations in the LD/CD group. In vitro, memantine
      inhibited diaphragmatic responses to indirect stimulation. Values of nAchR alpha
      subunit mRNA (microg/dl) were 0.7+/-0.16 (control), 0.13+/-0.11 (memantine),
      2.3+/-0.94 (LD/CD), and 1.18+/-0.71 (both drugs) (p<0.05). CONCLUSIONS: Memantine
      inhibits neuromuscular transmission in vitro and with in vivo treatment. LD/CD
      treatment enhances neuromuscular transmission. Clinical implications need further
      investigation.

PMID- 19865052
TI  - Mental representation of subjective pleasure of partnered experiences in women's
      brain conveyed through event-related fMRI.
AB  - BACKGROUND: Functional neuroimaging demonstrates a combined role of central and
      peripheral mechanisms in human sexual response. Nevertheless, inter-individual
      subjective differences remain unresolved. Since Freud, controversy remains
      regarding the similarity of each type of partnered sexual pleasure experience.
      The authors hypothesized that the neural networks sustaining the memory of all
      types of subjective partnered sexual pleasure experiences might interact with the
      insula, a key brain area for integrating somatic experiences. MATERIAL/METHODS:
      Using a 3T Phillips MRI scanner, brain activity elicited when 29 healthy female
      volunteers were exposed to subliminal presentation of their sexual partner's
      names, an approach to investigating the brain network sustaining the mental
      representation of their partner, was assessed. This brain activity was compared
      with scores from the Female Sexual Functioning Index on satisfaction and the
      typologies of their partnered orgasmic experiences. No orgasmic responses were
      recorded during fMRI. This approach allowed the investigation of the memory of
      the different types of stored partnered orgasmic experiences. RESULTS: The memory
      of partnered pleasure obtained by clitoral stimulation correlated with brain
      responses in the left insula only, while that of partnered pleasure by sexual
      intercourse correlated with the left insula and also with the right superior
      temporal gyrus, thalamus, and right inferior prefrontal gyrus. CONCLUSIONS: The
      results suggest that the memory of sexual experiences is integrated a posteriori
      at different levels (i.e. by different neural networks) in a woman's brain. The
      authors believe these findings will open a new avenue towards understanding inter
      and intra-individual differences in woman's sexual mind.

PMID- 19865053
TI  - Remifentanil bolus dose is a safe procedure to control intense noxious stimuli in
      hypertensive neurosurgical patients.
AB  - BACKGROUND: Patients with hypertension may be more prone to develop hypotension
      as a consequence of opioid administration under general anesthesia. The
      hemodynamic and bispectral index responses to a remifentanil bolus in
      neurosurgical hypertensive patients under target-controlled infusion with
      propofol and remifentanil are addressed. MATERIAL/METHODS: Ten healthy patients
      and 10 patients with diagnosed hypertension under pharmacological treatment were
      studied. A 2 microg/kg remifentanil bolus was administered to all patients before
      skin incision under target-controlled infusion with propofol and remifentanil.
      Mean arterial pressure, heart rate, and the area under the curve for the
      bispectral index of the electroencephalogram were analyzed within the groups and
      compared between them every 30 seconds for two minutes following the bolus.
      RESULTS: Two minutes after the remifentanil bolus, remifentanil predicted effect
      site concentrations reached maximum values of 8.46+/-0.91 ng/ml and 9.74+/-1.29
      ng/ml in the healthy and hypertensive patients, respectively. Both groups showed
      a significant decrease in mean arterial pressure, heart rate, and in the area
      under the curve for the bispectral index. Mean arterial pressure decreased by
      17.3+/-10% and 24+/-9%, heart rate by 11.1+/-8% and 12+/-8%, and the bispectral
      index by 13+/-9.2% and 8.6+/-8.4% in the healthy and hypertensive patients,
      respectively, 120 seconds after the remifentanil bolus. CONCLUSIONS: In a
      clinical situation in which high remifentanil doses may be required, hypertensive
      patients are expected to have hemodynamic and bispectral index responses similar
      to those observed in healthy patients.

PMID- 19865054
TI  - Intraocular pressure measurements with the newly reconfigured Ocuton S*TT-MV self
      tonometer in comparison to Goldmann applanation tonometry in glaucoma patients.
AB  - BACKGROUND: This study compared the new Ocuton S*TT-MV to the Ocuton S (former
      configuration) and GAT. The effect of the reconfiguration on measuring accuracy
      and device handling of glaucoma patients was evaluated. MATERIAL/METHODS: 101
      glaucoma patients performed self-measurements using the old Ocuton S and the
      Ocuton S*TT-MV. The new Ocuton S*TT-MV automatically verifies the applanated
      area. We used GAT as the gold standard reference. Three series of measurements
      were performed in random order. RESULTS: The mean IOP was 18.3+/-4.2 mmHg with
      Ocuton S, 17.5+/-3.6 mmHg with the reconfigured Ocuton S*TT-MV, and 15.1+/-3.4
      mmHg with GAT. IOP ranged from 9 to 30.5 mmHg with GAT, 7 to 42 mmHg with Ocuton
      S*TT-MV, and 5 to 38 mmHg with the old Ocuton S. The mean difference between the
      old Ocuton S and GAT was 3.2+/-3.5 mmHg, between Ocuton S*TT-MV and GAT 2.4+/-3.3
      mmHg, and between old and new Ocuton S 0.9+/-2.9 mmHg (p<0.01). The standard
      deviation within an individual row of 4 readings per eye with the old Ocuton S
      averaged 1.9 mmHg, while with the new Ocuton S*TT-MV the standard deviation
      averaged 1.7 mmHg. This measuring accuracy showed no age correlation for either
      self-tonometer (old Ocuton S: coefficient of correlation R=0.2; Ocuton S*TT-MV:
      coefficient of correlation R=0.053). CONCLUSIONS: The newly reconfigured Ocuton
      S*TT-MV improves measuring accuracy significantly and approaches the accuracy
      achieved using GAT. Improved usability of self-tonometers has clinical relevance,
      as patients don't have to check the corneal cast on the measuring prism. This
      could lead to an increased usage of self-tonometry in glaucoma monitoring.

PMID- 19865055
TI  - Elevated markers of thrombin generation and fibrinolysis in patients with active
      and quiescent ulcerative colitis.
AB  - BACKGROUND: Prothrombotic abnormalities within the coagulation system, the
      presence of microvascular thrombi in intestinal mucosa, and the increased risk of
      thromboembolic complications in patients with Inflammatory bowel disease, suggest
      that a hypercoagulable state may be an important contributing factor in disease
      pathogenesis. The activation of the coagulation system in a cohort of ulcerative
      colitis patients was investigated. MATERIAL/METHODS: Markers of coagulation
      activation in blood (thrombin-antithrombin complex, TAT; prothrombin fragments 1
      and 2, F1+2; and D-dimers) and markers of inflammation (erythrocyte sedimentation
      rate, ESR; C-reactive protein, CRP; and fibrinogen) were measured in 38 patients
      with active and 13 patients with long-standing quiescent ulcerative colitis.
      Disease activity was assessed by clinical, endoscopic, and histological criteria.
      The markers of coagulation activation were also measured in 28 healthy
      volunteers. RESULTS: There were no differences in TAT, F1+2, and D-dimer plasma
      levels between active and inactive ulcerative colitis. D-dimer and F1+2 levels
      were significantly higher in the active ulcerative colitis patients than in the
      healthy controls. Plasma levels of TAT, F1+2, and D-dimers did not differ between
      inactive ulcerative colitis patients and healthy controls. However, both active
      and inactive ulcerative colitis patients had significantly higher proportions of
      elevated (above-normal) values of coagulation markers than the healthy controls.
      Correlation analyses revealed strong correlation between ESR, fibrinogen, and D
      dimers, which also correlated with the severity and extent of ulcerative colitis.
      CONCLUSIONS: A chronic low-grade activation of coagulation exists in ulcerative
      colitis, regardless of disease activity, and it might be implicated in disease
      pathogenesis.

PMID- 19865056
TI  - Ocular circulation in systemic lupus erythematosus.
AB  - BACKGROUND: Mean vascular resistance in the retrobulbar arteries of SLE patients
      and the statistical relationship between its parameters and the presence of
      certain antibodies were determined. MATERIAL/METHODS: Forty-three eyes of 43 SLE
      female patients aged 46.28+/-8.45 years with disease duration of 10.03+/-7.96
      years were examined. Physical and ophthalmic examinations with assessments of the
      immunological markers ANA/IgG-IgM, aCL, anti-beta2GPI, LA, and anti-dsDNA
      antibodies were performed. color Doppler imaging (CDI) was used in the OA, CRA,
      LPCA, and MPCA vessels. The vascular resistance indices (RIs) were compared with
      those of 43 eyes of 43 female controls. Covariance and multiple regression
      analysis with chi squared, Pearson, Shapiro-Wilk, and Levene tests were used in
      the statistical analysis (significance levels at p<or=0.01 and p<or=0.05).
      RESULTS: Significantly increased RIs in the OA, CRA, LPCA, and MPCA were
      recorded. aCL, abeta2GPI, and LAC correlated significantly with increased RI in
      the CRA. SLE diagnosis significantly correlated with RI in the OA and PCAs.
      Significant relationship between age and RI in the CRA and LPCA was detected.
      CONCLUSIONS: Retrobulbar resistance disturbances were detected in SLE patients by
      CDI. SLE diagnoses and presence of aPLs antibodies were associated with an
      increased resistivity index in ophthalmic and retino-choroidal vessels.

PMID- 19865057
TI  - Susceptibility pattern of E. coli-associated urinary tract infection (UTI): a
      comparison of spinal cord injury-related and nosocomial UTI.
AB  - BACKGROUND: Evolving resistant uropathogens are associated with elevated risk of
      morbidity and mortality both in nosocomial and in spinal cord injury (SCI)
      associated urinary tract infections (UTIs). Clinico-epidemiological studies are
      therefore essential to facilitate empirical therapy and decrease treatment time.
      MATERIAL/METHODS: This study was performed at Al-Zahra Hospital, Isfahan
      University of Medical Sciences, Isfahan, Iran. All E. coli-infected UTI
      hospitalized patients, except those with symptoms of UTI prior to admission or in
      the first 48 hours of hospitalization, were included in this study as group A.
      All E. coli-infected SCI-associated UTIs were included in group B. Urine samples
      were cultured and the MICs of nine antibiotics on the isolated bacteria were
      determined by the gradient concentration method with E. coli ATCC25922 as the
      standard control. RESULTS: Antibiotic-resistant uropathogens were more prevalent
      among the nosocomial than the SCI-associated UTIs. The antibiotic-resistance
      rates of isolated E. coli in the nosocomial and SCI-associated UTIs were 13.9%
      and 5.9% for amikacin, 65% and 40.5% for ceftazidime, 69.8% and 32.4% for
      ceftriaxone, 50% and 41.2% for ciprofloxacin, 56.9% and 13.6% for gentamicine,
      2.1% and 0% for imipenem, 3.9% and 0% for meropenem, and 73.6% and 63.6% for
      trimethoprim/sulfamethoxazole, respectively. Only resistance to nalidixic acid
      was mildly higher in SCI E. coli. The MIC50 of all the antibiotics except
      nalidixic acid was higher in nosocomial E. coli. CONCLUSIONS: Despite more risk
      factors for antibiotic-resistant E. coli in SCI patients, antibiotic-resistant E.
      coli was observed more in nosocomial UTIs, which may be attributable to the
      hospital environment.

PMID- 19865058
TI  - Influence of erythropoietin therapy on serum prohepcidin levels in dialysis
      patients.
AB  - BACKGROUND: Anemia is a common finding in dialysis patients. Recent evidence has
      accrued that hepcidin, an iron regulatory peptide, may play a crucial role in the
      pathophysiology of this condition. This study investigated the effect of
      erythropoietin (EPO) therapy on serum levels of prohepcidin, the pro-hormone of
      hepcidin, in patients with end-stage renal disease (ESRD) undergoing chronic
      dialysis treatment. MATERIAL/METHODS: A total of 40 ESRD patients with renal
      anemia receiving either hemodialysis or peritoneal dialysis were included in this
      study. The patients were randomly allocated to EPO (subcutaneous 2000 microg
      three times weekly) plus parenteral iron (n=23) or parental iron only (n=17).
      Serum prohepcidin levels were measured before and at the end of the study.
      RESULTS: The two groups were comparable in their demographic and laboratory
      characteristics. No significant differences were found in hemoglobin, hematocrit,
      iron store indices, or serum levels of prohepcidin at study entry. Significant
      increases in both hemoglobin and hematocrit as well as a decrease in serum
      prohepcidin level were evident in the EPO group at the end of the 6-month follow
      up in comparison with their values at study entry compared with the control group
      (P<0.01). CONCLUSIONS: It is concluded that EPO therapy, besides enhancing
      erythropoiesis, modulates serum prohepcidin levels in dialysis patients.

PMID- 19865059
TI  - A comparison of different treatment managements in patients with acute deep vein
      thrombosis by the effects on enhancing venous outflow in the lower limb.
AB  - BACKGROUND: This study aimed at evaluating the benefits of the traditional
      management of acute deep vein thrombosis (DVT), subcutaneous (sc) administration
      of low-molecular-weight heparin (LMWH) one dose a day and bed rest, and LMWH with
      compression stocking and early ambulation compared with LMWH with pneumatic
      compression (PC) in patients with DVT. MATERIAL/METHODS: Forty-eight consecutive
      patients with DVT were separated evenly into four groups. Group A received
      intravenous unfractionated heparin, group B received sc injection of enoxaparin
      sodium and bed rest, group C received sc injection of enoxaparin sodium and thigh
      length compression stockings, and group D received sc injection of enoxaparin
      sodium and PC for periods of up to 7 days. RESULTS: Comparing days 0 and 7,
      significant differences were determined in each group regarding differences in
      circumference of the two legs at the thigh and calf levels and the visual
      analogue scale (VAS) of pain, and in groups B, C, and D regarding the Lowenberg
      test for diseased and healthy legs (p<0.001). Between days 0 and 7, significant
      differences were found in the superficial femoral artery, superficial femoral
      vein, femoral vein, and the popliteal vein within groups A and D (p<0.05).
      CONCLUSIONS: Traditional management, sc administration of low-molecular-weight
      heparin, and pneumatic compression of patients with DVT led to a faster reduction
      of leg swelling and pain and to increased volume flow through the deep veins of
      the legs.

PMID- 19865060
TI  - Successful treatment of a critical burn patient with obstinate hyperglycemia and
      septic shock from pan-drug-resistant strains.
AB  - BACKGROUND: The treatment of critical burn patients involves fluid resuscitation,
      homeostasis, prevention of infection, support and maintenance of organ functions,
      nutritional support, and wound repair. Correct management of these problems is a
      fierce challenge facing burn clinicians. This report presents a critical burn
      patient with obstinate hyperglycemia and septic shock from pan-drug-resistant
      strains. CASE REPORT: A 41-year-old female with a 96% total body surface area
      (TBSA) burn developed a series of severe complications during the course of
      treatment, including rare obstinate hyperglycemia and septic shock from pan-drug
      resistant Acinetobacter baumanii. Several aspects of the applied treatment are
      emphasized: an immediate effort to close the wound, the appropriate use of
      antibiotics, and the extraordinarily large amounts of insulin for intensive
      therapy to control blood sugar. CONCLUSIONS: The critical burn patient developed
      a series of severe complications during the course of treatment. Correct
      management of these complications is crucial to success in the treatment of such
      patients.

PMID- 19865061
TI  - Ophthalmomyiasis is not only a problem for rural regions of Eastern Anatolia of
      Turkey.
AB  - BACKGROUND: Ophthalmomyiasis externa results from infestation of the conjunctiva
      by the larval or maggot form of Oestrus ovis. It is common in sheep-farming
      areas, especially in Mediterranean countries. CASE REPORT: A 40-year-old man was
      admitted to the ophthalmology outpatient clinic at State Hospital. He complained
      of a foreign-body sensation. He was living in a city center in Eastern Anatolia
      of Turkey. The larvae were removed and antibiotic drops and ointment were given
      to the patient. The larvae were first-instar Oestrus ovis larvae. CONCLUSIONS:
      The authors consider ophthalmomyiasis to be not only a problem of rural areas and
      subsequent examination is very important to ensure that no complications have
      occurred. It is hoped that this case encourages physicians to be aware of the
      diagnosis of ophthalmomyiasis externa and its complication and treatment.

PMID- 19865062
TI  - Influence of resting periods on polyethylene wear in a knee simulator study.
AB  - BACKGROUND: Knee wear simulator studies are performed to evaluate the wear
      behavior of implants. These wear studies simulate in vivo situations as closely
      as possible. Simulation of the human gait cycle is often carried out continuously
      according to international standards. However, implants are not loaded
      continuously in vivo, so it might be advisable to implement resting periods in
      which no motion occurs. MATERIAL/METHODS: In the present study the influence of
      resting periods on the wear behavior of a commercial implant was analyzed using a
      force-controlled AMTI knee simulator. RESULTS: The wear rates were 2.27+/-0.23
      mg/10(6) cycles for a simulation with resting periods and 2.85+/-0.27 mg/10(6)
      cycles for a reference simulation without resting periods. There was no
      significant difference (p=0.22) in wear behavior between these two tests.
      CONCLUSIONS: The present study shows that continuous simulation without the
      implementation of resting periods is a valid approach for assessing the wear of
      knee implants.

PMID- 19865063
TI  - The effects of alprazolam on tinnitus: a cross-over randomized clinical trial.
AB  - BACKGROUND: Tinnitus remains a phenomenon with an unknown pathophysiology and for
      which few therapeutic measures are available. To date there has been insufficient
      evidence to support the use of alprazolam in the treatment of tinnitus. We sought
      to evaluate the efficacy of alprazolam for relief of tinnitus. MATERIAL/METHODS:
      Thirty-six tinnitus sufferers participated in this cross-over, randomized, triple
      blind, placebo-controlled trial. Inclusion criteria included patients between
      ages 21 and 65, with a complaint of non-pulsatile tinnitus of more than 1 year
      duration. Patients with depressive or anxiety disorders were excluded, as were
      those using hearing aids. Participants received alprazolam 1.5 mg daily versus
      placebo in each period. Primary outcome variables included the Tinnitus Handicap
      Inventory (THI), a Visual Analog Scale (VAS), and tinnitus loudness. RESULTS:
      Thirty patients completed the study. The average age of patients was 47.58+/-7.65
      years. Alprazolam in comparison with placebo did not result in statistically
      significantly greater relief in THI score and tinnitus loudness. There was a
      significant improvement in VAS score in the alprazolam group compared with the
      placebo group (p<0.001). CONCLUSIONS: These results suggest that although
      alprazolam did not improve the THI score or sensation level of loudness
      significantly, it has a desirable effect on VAS. Further work is needed to
      determine the beneficial effects of alprazolam in distressed or depressed
      patients.

PMID- 19865064
TI  - Prevalence and antimicrobial susceptibility of Escherichia coli in outpatient
      urinary isolates in Izmir, Turkey.
AB  - BACKGROUND: Knowledge of antimicrobial resistance pattern in Escherichia coli,
      the predominant pathogen associated with urinary tract infection (UTI), is
      important as a guide in selecting empirical antimicrobial therapy. The aim of
      this study was to determine the antibiotic susceptibility patterns of E. coli
      strains isolated from adult outpatients with UTI, in Izmir, Turkey.
      MATERIAL/METHODS: This study was performed with isolates from outpatients with
      UTI, collected from 5 university and tertiary-care hospitals in Izmir, Turkey.
      Isolates were analyzed by standard methods and antimicrobial susceptibility
      testing was performed by Kirby-Bauer disc diffusion method. RESULTS: A total of
      4,534 E. coli strains (3,449 females and 1,085 males) were examined. Antibiotic
      resistance rates of the isolates for female and male, respectively: Ampicillin
      (61.8%, 78.7%), amoxicillin-clavulanic acid (36.6%, 59.1%), cefuroxime (22.5%,
      41.3%), cefotaxime (18.2%, 35.8%), piperacillin-tazobactam (11.6%, 31.2%),
      amikacin (8.3%, 13.9%), gentamicin (24.9%, 40%), trimethoprim-sulfamethoxazole
      (42.1%, 57.3%), and ciprofloxacin/norfloxacin (42.1%, 63.3%). Extended spectrum
      beta-lactamase rate was found to be 18.3% and 26.1% for females and males,
      respectively. The isolates were significantly more resistant to all antibiotics
      in men than in females in this study (p<0.001). CONCLUSIONS: The most important
      finding of our study is that a considerable proportion of the studied E. coli
      isolates were resistant to most antibiotics except amikacin. These data provide
      useful information for clinicians in determining the appropriate empirical
      antimicrobial regimen, and help authorities to formulate antibiotic prescription
      policies.

PMID- 19865065
TI  - The monitoring role of otoacoustic emissions and oxidative stress markers in the
      protective effects of antioxidant administration in noise-exposed subjects: a
      pilot study.
AB  - BACKGROUND: Oxidative stress has been recently identified as the pivotal pathway
      of cochlear damage. The aims of this study were to evaluate whether distortion
      product otoacoustic emissions (DPOAEs) can discriminate normal subjects with a
      risk of damage induced by sound exposure, the effectiveness of OAEs in monitoring
      the protective effects of Coenzyme Q10 terclatrate (QTer), and the role of blood
      parameters in monitoring preventive therapies. MATERIAL/METHODS: Twenty
      volunteers were randomized to two groups: the first (n=10) was treated with Q-Ter
      (200 mg orally once daily) for 7 days before noise exposure and the second group
      was treated with placebo using the same schedule. All participants were exposed
      to white noise of 90 dB HL for 15 minutes. DPOAEs and pure-tone audiometry (PTA)
      were measured before and 1 h, 16 h, and 7 and 21 days after exposure.
      Inflammatory and oxidative stress parameters were measured before and 2 and 24 h
      after exposure. RESULTS: In the placebo group, DPOAE amplitudes were reduced 1
      and 16 h after exposure compared with the baseline values (p<0.05). In the Q-Ter
      group, DPOAEs did not show any significant difference between baseline and post
      exposure (p>0.1). PTA threshold values in the Q-Ter and placebo groups did not
      differ before and after exposure. No significantly different levels of the
      inflammatory markers were observed in the Q-Ter and placebo groups at the
      different time points. CONCLUSIONS: This pilot study confirms that DPOAEs
      represent a sensitive test for monitoring the effects of noise in preclinical
      conditions and pharmacological treatment.

PMID- 19865066
TI  - Cyclophilin A: potential functions and therapeutic target for human cancer.
AB  - Cyclophilin A (CypA) is a cytosolic binding protein of the immunosuppressive drug
      cyclosporin A. CypA has an activity of peptidylprolyl cis-trans isomerase, which
      may play important roles in protein folding, trafficking, assembly, immune
      modulator and cell signaling. Secreted form of CypA can act as growth factors in
      several cell types. On the other hand, CypA also involves in pathogenesis in
      several diseases including viral infection, cardiovascular disease and cancer.
      For example, CypA protein displays an unusually high expression in several cancer
      types and correlates with poor outcome of the patients. In this review, we have
      focused on the recently available clinical data of altered CypA expression in
      various tumor tissues and cell lines and discussed contributions and potential
      molecular mechanisms of CypA to tumor progression and clinical association. CypA
      could promote cancer cell proliferation, anti-apoptosis, cell migration/invasion
      and drug resistant in various cancer cell types. The mechanism by which CypA
      contributes to cancer progression appears to involve a complex interplay of
      proteins and pathways including membrane receptor for CypA, CD147, and CypA
      binding partners inside the cells. CypA could be used as a molecular target for
      cancer therapy.

PMID- 19865067
TI  - Regenerative medicine: advances in new methods and technologies.
AB  - The articles published in the journal Cell Transplantation - The Regenerative
      Medicine Journal over the last two years reveal the recent and future cutting
      edge research in the fields of regenerative and transplantation medicine. 437
      articles were published from 2007 to 2008, a 17% increase compared to the 373
      articles in 2006-2007. Neuroscience was still the most common section in both the
      number of articles and the percentage of all manuscripts published. The
      increasing interest and rapid advance in bioengineering technology is highlighted
      by tissue engineering and bioartificial organs being ranked second again. For a
      similar reason, the methods and new technologies section increased significantly
      compared to the last period. Articles focusing on the transplantation of stem
      cell lineages encompassed almost 20% of all articles published. By contrast, the
      non-stem cell transplantation group which is made up primarily of islet cells,
      followed by biomaterials and fetal neural tissue, etc. comprised less than 15%.
      Transplantation of cells pre-treated with medicine or gene transfection to
      prolong graft survival or promote differentiation into the needed phenotype, was
      prevalent in the transplantation articles regardless of the kind of cells used.
      Meanwhile, the majority of non-transplantation-based articles were related to new
      devices for various purposes, characterization of unknown cells, medicines, cell
      preparation and/or optimization for transplantation (e.g. isolation and culture),
      and disease pathology.<br />

PMID- 19865068
TI  - Etiopathogenesis and management of high myopia. Part II.
AB  - High myopia (HM) is defined as refractive error above -6.0 D (-8.0 diopters) with
      axial eyeball length above 26 mm, and is connected with the process of excessive
      myopisation. HM is not a homogenous disease. HM is considered to be inherited in
      3 different patterns: dominant, autosomal recessive, and X-linked. Many genetic
      mutations linked to the development of HM have been described, including high
      grade myopia, and MYP1-16; different patterns of inheritance may reflect
      different types of HM. Over 150 genetic syndromes are associated with HM. The
      clinical state of the HM eyeball may also depend on environmental risk factors
      influencing the progression of refractive error. The complexity of
      etiopathogenesis makes it difficult to distinguish to what extent the development
      of HM is related to genetics versus exposure to environmental factors. HM remains
      a leading cause of visual loss. HM and its complications are considered to be one
      of the most significant causes of blindness and visual impairment in young,
      professionally active people, becoming an important social problem. Contemporary
      data concerning genetic factors, family aggregation, and epidemiological data of
      visual impairment connected with HM are presented in this paper. Therapeutic
      options for this refractive error are presented as well.

PMID- 19865069
TI  - Formulations of dietary supplements and herbal extracts for relaxation and
      anxiolytic action: Relarian.
AB  - Dietary supplements are widely used for desired effects on memory, insomnia, mood
      and anxiety. This review focuses on supplements which have anxiolytic or mild
      relaxation properties and enhance mood. For example, Kava (Piper methysticum) is
      reported to have anaxiolytic actions and to reduce tension through skeletal
      muscle relaxation. Dried passion flower (genus Passiflora) is reported to reduce
      insomnia and hysteria. Skullcap (genus Scutellaria), hops (Humulus lupulus),
      lemon balm (Melissa officinalis) and Valerian (Valeriana officinalis) root are
      all herbs reported as anaxiolytic calming agents. Further, extracts of Magnolia
      and Phellondendron bark are mild sedatives. Supplements such as gamma
      aminobutyric acid (GABA), theanine, tryptophan and 5-hydroxytryptophan (5-HTP)
      are reported to promote relaxation. In general, these supplements appear to act
      as GABA receptor agonists or to boost GABA levels, although Kava inhibits both
      norephinephrine uptake and sodium and potassium channels and 5-HTP may act
      through elevation of serotonin. While questions remain in the literature
      regarding the medicinal value of these supplements in treating mood and anxiety
      disorders, based on cellular and animal studies as well as human clinical trials
      the literature supports a role for these preparations as useful alternatives in
      the management of the stress and anxiety of everyday life.

PMID- 19865070
TI  - Denaturing urea polyacrylamide gel electrophoresis (Urea PAGE).
AB  - Urea PAGE or denaturing urea polyacrylamide gel electrophoresis employs 6-8 M
      urea, which denatures secondary DNA or RNA structures and is used for their
      separation in a polyacrylamide gel matrix based on the molecular weight.
      Fragments between 2 to 500 bases, with length differences as small as a single
      nucleotide, can be separated using this method(1). The migration of the sample is
      dependent on the chosen acrylamide concentration. A higher percentage of
      polyacrylamide resolves lower molecular weight fragments. The combination of urea
      and temperatures of 45-55 degrees C during the gel run allows for the separation
      of unstructured DNA or RNA molecules. In general this method is required to
      analyze or purify single stranded DNA or RNA fragments, such as synthesized or
      labeled oligonucleotides or products from enzymatic cleavage reactions. In this
      video article we show how to prepare and run the denaturing urea polyacrylamide
      gels. Technical tips are included, in addition to the original protocol (1,2).

PMID- 19865071
TI  - Occupational exposure to benzene at the ExxonMobil refinery in Baytown, TX (1978
      2006).
AB  - Although occupational benzene exposure of refinery workers has been studied for
      decades, no extensive analysis of historical industrial hygiene data has been
      performed focusing on airborne concentrations at specific refineries and tasks.
      This study characterizes benzene exposures at the ExxonMobil Baytown, TX,
      refinery from 1978 to 2006 to understand the variability in workers' exposures
      over time and during different job tasks. Exposures were grouped by operational
      status, job title, and tasks. More than 9000 industrial hygiene air samples were
      evaluated; approximately 4000 non-task (> 3 h) and 1000 task-related (< 3 h)
      personal samples were considered. Each sample was assigned to one of 27 job
      titles, 29 work areas, and 16 task bins (when applicable). Process technicians
      were sampled most frequently, resulting in the following mean benzene
      concentrations by area: hydrofiner (n=245, mean=1.3 p.p.m.), oil movements
      (n=286, mean=0.23 p.p.m.), reformer (n=575, mean=0.10 p.p.m.), tank farm (n=9,
      mean=0.65 p.p.m.), waste treatment (n=446, mean=0.13 p.p.m.), and other areas
      (n=460, mean=0.062 p.p.m.). The most frequently sampled task was sample
      collection (n=218, mean=0.40 p.p.m.). Job title and area did not significantly
      impact task-related exposures. Airborne concentrations were significantly lower
      after 1990 than before 1990. Results of this task-focused study may be useful
      when analyzing benzene exposures at other refineries.

PMID- 19865072
TI  - Assessment of cancer risks due to environmental exposure to asbestos.
AB  - In a rural area widespread pollution of friable and non-friable waste products
      was present, used to harden dirt tracks, yards, and driveways during 1935-1974.
      Exposure to environmental asbestos was assessed by a site approach, based on
      number of polluted sites within postal code areas, and by a household approach,
      based on number of households in the close vicinity to polluted sites within
      postal code areas. Based on asbestos soil investigations, 293 sites were
      identified with asbestos waste material at the surface, of which 77% contained
      crocidolite fibres as well as chrysotile fibres. The 293 sites-at-risk varied
      from 5 m(2) to 2722 m(2) and were surrounded by 347 households within 100 m of
      these sites. Distance to the plant was associated with the number of sites
      (r=0.36), and with the number of households (r=0.52). However, categorization of
      postal code areas into low, intermediate or high likelihood of exposure to
      asbestos showed a modest agreement between the site and household approach. In
      the site approach a total of 2.3 million person-years at risk were estimated with
      an average exposure of 1674 fibres/m(3) and an expected 1.8 cases of malignant
      mesothelioma each year. The household approach resulted in estimates of 1.2
      million person-years at risk, and 0.9 cases of malignant mesothelioma per year,
      respectively. This study illustrates that asbestos waste on the surface of roads
      and yards in an area with over 130,000 inhabitants may result in long-term
      exposure to asbestos that will cause several cases of malignant mesothelioma each
      year. Although distance to plant, number of polluted sites and number of exposed
      household were associated, the modest agreement among these measures of exposure
      indicate that the exposure assessment strategy chosen in a particular study may
      result in considerable misclassification. Without detailed information on
      individual behaviour within the polluted area, it is difficult to show that a
      more individually oriented approach will perform better than an ecological
      approach.

PMID- 19865073
TI  - Personal exposures to traffic-related particle pollution among children with
      asthma in the South Bronx, NY.
AB  - Personal exposures to fine particulate matter air pollution (PM(2.5)), and to its
      traffic-related fraction, were investigated in a group of urban children with
      asthma. The relationships of personal and outdoor school-site measurements of
      PM(2.5) and elemental carbon (EC) were characterized for a total of 40 fifth
      grade children. These students, from four South Bronx, NY schools, each carried
      air pollution monitoring equipment with them for 24 h per day for approximately 1
      month. Daily EC concentrations were estimated using locally calibrated
      reflectance of the PM(2.5) samples. Personal EC concentration was more closely
      related to outdoor school-site EC (median subject-specific: r=0.64) than was
      personal PM(2.5) to school-site PM(2.5) concentration (median subject-specific:
      r=0.33). Regression models also showed a stronger, more robust association of
      school site with personal measurements for EC than those for PM(2.5). High
      traffic pollution exposure was found to coincide with the weekday early morning
      rush hour, with higher personal exposures for participants living closer to a
      highway (<500 ft). A significant linear relationship of home distance from a
      highway with personal EC pollution exposure was also found (up to 1000 ft). This
      supports the assumptions by previous epidemiological studies using distance from
      a highway as an index of traffic PM exposure. These results are also consistent
      with the assumption that traffic, and especially smoke emitted from diesel
      vehicles, is a significant contributor to personal PM exposure levels in children
      living in urban areas such as the South Bronx, NY.

PMID- 19865074
TI  - Maternal exposure to perfluorinated acids and fetal growth.
AB  - The widespread detection of perfluorinated acids (PFAs) in humans and known
      developmental toxicity in animals has raised concern about their potential
      effects on human reproductive health. Our objective was to determine whether
      increasing maternal exposure to PFAs is associated with adverse effects on fetal
      growth and length of gestation in women giving birth in Alberta, Canada. We
      examined the concentrations of perfluorooctanoic acid (PFOA), perfluorooctane
      sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) in a cohort of 252
      pregnant women who gave birth to live singletons. Each of the women had undergone
      an early second trimester prenatal screen, and her serum was analyzed for PFA
      concentrations. Data on infant and maternal variables were collected from the
      delivery record completed at birth. Adjusted changes in birth weight per natural
      log (ng/ml) of PFOA (median 1.5 ng/ml), PFHxS (median 0.97 ng/ml), and PFOS
      (median 7.8 ng/ml) were -37.4 g (95% confidence interval (CI): -86.0 to 11.2 g),
      21.9 g (-23.4 to 67.2 g), and 31.3 g (-43.3 to 105.9 g), respectively. Mean birth
      weight z-score, standardized for gestational age and gender, length of gestation,
      and risk of preterm birth did not appear to be influenced by maternal PFA
      exposure. When PFA concentrations were divided into tertiles, similar patterns
      were observed. These results suggest that maternal PFA exposure has no
      substantial effect on fetal weight and length of gestation at the concentrations
      observed in this population.

PMID- 19865075
TI  - Atherosclerotic renovascular disease in the United States.
AB  - Atherosclerotic renovascular disease (ARVD) is an increasingly recognized
      clinical condition that is diagnosed predominantly in older patients. Here we
      used annual United States Medicare 5% Denominator Files and studied 16,036,904
      patients, 66 years of age and older, to quantify trends in diagnostic rates,
      associations, treatment, and outcomes of ARVD over a 13-year period. Overall,
      there was an ARVD rate of 3.09 per 1000 patient-years, which rose progressively
      with an adjusted hazard ratio of 3.35, comparing data from 1992 to 2004. Within 6
      months of disease diagnosis, 13.4% of patients had undergone revascularization. A
      biphasic pattern of revascularization was found where the adjusted hazard ratios
      significantly increased in a progressive manner until 1999, following which there
      was a decline through 2004, which was not significant. The method of
      revascularization changed markedly over time with endovascular intervention
      steadily replacing direct surgical revascularization. As a time-dependent
      variable, ARVD was associated with excess mortality in each calendar year, albeit
      with declining hazard ratio estimates in more recent years. Among patients with
      this disease, revascularization was associated with mortality adjusted hazard
      ratios <1 in each year. Our study shows the diagnosis of ARVD has substantially
      risen in the United States but the survival implications were not fully explained
      by other comorbid vascular diseases.

PMID- 19865076
TI  - Effects of treatment for tobacco dependence on resting cerebral glucose
      metabolism.
AB  - While bupropion HCl and practical group counseling (PGC) are commonly used
      treatments for tobacco dependence, the effects of these treatments on brain
      function are not well established. For this study, 54 tobacco-dependent cigarette
      smokers underwent resting (18)F-fluorodeoxyglucose-positron emission tomography
      (FDG-PET) scanning before and after 8 weeks of treatment with bupropion HCl, PGC,
      or pill placebo. Using Statistical Parametric Mapping (SPM 2), changes in
      cerebral glucose metabolism from before to after treatment were compared between
      treatment groups and correlations were determined between amount of daily
      cigarette usage and cerebral glucose metabolism. Compared with placebo, the two
      active treatments (bupropion HCl and PGC) had reductions in glucose metabolism in
      the posterior cingulate gyrus. Further analysis suggested that PGC had a greater
      effect than bupropion HCl on glucose metabolism in this region. We also found
      positive correlations between daily cigarette use and glucose metabolism in the
      left occipital gyrus and parietal-temporal junction. There were no significant
      negative correlations between daily cigarette use and glucose metabolism. Our
      findings suggest that bupropion HCl and PGC reduce neural activity much as the
      performance of a goal-oriented task does in the default mode network of the
      brain, including the posterior cingulate gyrus. Thus, this study supports the
      theory that active treatments for tobacco dependence move the brain into a more
      goal-oriented state.

PMID- 19865077
TI  - Endoplasmic reticulum stress and intestinal inflammation.
AB  - The intestinal epithelial cell (IEC) is increasingly recognized to play a
      prominent role as an important intermediary between the commensal microbiota and
      the intestinal immune system. Moreover, it is now recognized that intestinal
      inflammation in inflammatory bowel disease (IBD) may arise primarily from IEC
      dysfunction due to unresolved endoplasmic reticulum (ER) stress as a consequence
      of genetic disruption of X box binding protein-1 function. In addition to primary
      (genetic) abnormalities of the unfolded protein response, a variety of secondary
      (inflammation and environmental) factors are also likely to be important
      regulators of ER stress. ER stress pathways are also well known to regulate (and
      be regulated by) autophagy pathways. Therefore, the host's ability to manage ER
      stress is likely to be a major pathway in the pathogenesis of intestinal
      inflammation that arises primarily from the IEC. Herein we discuss ER stress in
      the IEC as both an originator and perpetuator of intestinal inflammation in IBD.

PMID- 19865079
TI  - Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo
      pediatric kidney transplant recipients.
AB  - The aim of this study was to develop a population pharmacokinetic model of
      tacrolimus in pediatric kidney transplant patients, identify factors that explain
      variability, and determine dosage regimens. Pharmacokinetic samples were
      collected from 50 de novo pediatric kidney transplant patients (age 2-18 years)
      who were on tacrolimus treatment. Population pharmacokinetic analysis of
      tacrolimus was performed using NONMEM, and the impact of variables (demographic
      and clinical factors, and CYP3A4-A5, ABCB1, and ABCC2 polymorphisms) was tested.
      The pharmacokinetic data were described by a two-compartment model that
      incorporated first-order absorption and lag time. The apparent oral clearance
      (CL/F) was significantly related to body weight (allometric scaling); in
      addition, it was higher in patients with low hematocrit levels and lower in
      patients with CYP3A5*3/*3. The population pharmacokinetic-pharmacogenetic model
      developed in de novo pediatric kidney transplant patients demonstrated that, in
      children, tacrolimus dosage should be based on weight, hematocrit levels, and
      CYP3A5 polymorphism. Individualization of therapy will enable the optimization of
      tacrolimus exposure, with resultant beneficial effects on kidney function in the
      initial post-transplantation period.

PMID- 19865078
TI  - Novel signaling interactions between proteinase-activated receptor 2 and Toll
      like receptors in vitro and in vivo.
AB  - Toll-like receptors (TLRs) and proteinase-activated receptors (PARs) function as
      innate immune biosensors in mucosal epithelial cells (ECs). We previously
      reported the functional and physical interactions between TLR4 and PAR(2). We
      have extended these findings herein by showing the cooperation between PAR(2) and
      TLR2, TLR3, or TLR4 for activation of nuclear factor-kappaB-dependent signaling
      in mucosal EC lines. In contrast, activation of PAR(2) negatively regulated TLR3
      dependent antiviral pathway, blunting the expression of TLR3/interferon
      regulatory factor-3 (IRF-3)-driven genes, as well as activation of IRF-3 and
      STAT1. Consistent with these in vitro observations, PAR(2)(-/-) and TLR4(-/-)
      mice, which were refractory to footpad edema induced by PAR(2) agonist peptide,
      were protected from mouse-adapted H1N1 influenza A virus-induced lethality when
      compared to wild-type (WT) mice. These data support and extend our recently
      described, novel model of PAR(2)-TLR4 "receptor cooperativity" and highlight the
      complexity of signaling integration between heterologous innate immune
      biosensors.

PMID- 19865080
TI  - Developmental pharmacogenetics: a general paradigm for application to neonatal
      pharmacology and toxicology.
AB  - Therapy in newborn infants presents unique challenges. The consequences of
      exposure of the fetus to medications and environmental contaminants in utero
      (following the mother's exposure to these) may present, in the newborn, as
      congenital malformations or adverse drug reactions or have unknown long-term
      consequences. Risk is not uniformly distributed across a population. Rather,
      pharmacogenomic principles assert that an individual's unique clinical, genomic,
      and environmental information can be used to accurately predict predisposition to
      risk. The challenge is to identify the specific factors--genetic and nongenetic-
      that contribute to increased risk.

PMID- 19865082
TI  - Do NSAIDs actually protect against myocardial infarction and death?

PMID- 19865084
TI  - Crystal structure of a bacterial homologue of the kidney urea transporter.
AB  - Urea is highly concentrated in the mammalian kidney to produce the osmotic
      gradient necessary for water re-absorption. Free diffusion of urea across cell
      membranes is slow owing to its high polarity, and specialized urea transporters
      have evolved to achieve rapid and selective urea permeation. Here we present the
      2.3 A structure of a functional urea transporter from the bacterium Desulfovibrio
      vulgaris. The transporter is a homotrimer, and each subunit contains a continuous
      membrane-spanning pore formed by the two homologous halves of the protein. The
      pore contains a constricted selectivity filter that can accommodate several
      dehydrated urea molecules in single file. Backbone and side-chain oxygen atoms
      provide continuous coordination of urea as it progresses through the filter, and
      well-placed alpha-helix dipoles provide further compensation for dehydration
      energy. These results establish that the urea transporter operates by a channel
      like mechanism and reveal the physical and chemical basis of urea selectivity.

PMID- 19865085
TI  - Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete
      formation.
AB  - The leading cause of infertility in men and women is quantitative and qualitative
      defects in human germ-cell (oocyte and sperm) development. Yet, it has not been
      possible to examine the unique developmental genetics of human germ-cell
      formation and differentiation owing to inaccessibility of germ cells during fetal
      development. Although several studies have shown that germ cells can be
      differentiated from mouse and human embryonic stem cells, human germ cells
      differentiated in these studies generally did not develop beyond the earliest
      stages. Here we used a germ-cell reporter to quantify and isolate primordial germ
      cells derived from both male and female human embryonic stem cells. By silencing
      and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding
      proteins (not transcription factors), we modulated human germ-cell formation and
      developmental progression. We observed that human DAZL (deleted in azoospermia
      like) functions in primordial germ-cell formation, whereas closely related genes
      DAZ and BOULE (also called BOLL) promote later stages of meiosis and development
      of haploid gametes. These results are significant to the generation of gametes
      for future basic science and potential clinical applications.

PMID- 19865086
TI  - Pediatric rheumatic disease: can molecular profiling predict the future in JIA?

PMID- 19865083
TI  - A limit on the variation of the speed of light arising from quantum gravity
      effects.
AB  - A cornerstone of Einstein's special relativity is Lorentz invariance-the
      postulate that all observers measure exactly the same speed of light in vacuum,
      independent of photon-energy. While special relativity assumes that there is no
      fundamental length-scale associated with such invariance, there is a fundamental
      scale (the Planck scale, l(Planck) approximately 1.62 x 10(-33) cm or E(Planck) =
      M(Planck)c(2) approximately 1.22 x 10(19) GeV), at which quantum effects are
      expected to strongly affect the nature of space-time. There is great interest in
      the (not yet validated) idea that Lorentz invariance might break near the Planck
      scale. A key test of such violation of Lorentz invariance is a possible variation
      of photon speed with energy. Even a tiny variation in photon speed, when
      accumulated over cosmological light-travel times, may be revealed by observing
      sharp features in gamma-ray burst (GRB) light-curves. Here we report the
      detection of emission up to approximately 31 GeV from the distant and short GRB
      090510. We find no evidence for the violation of Lorentz invariance, and place a
      lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an
      inverse wavelength dependence), subject to reasonable assumptions about the
      emission (equivalently we have an upper limit of l(Planck)/1.2 on the length
      scale of the effect). Our results disfavour quantum-gravity theories in which the
      quantum nature of space-time on a very small scale linearly alters the speed of
      light.

PMID- 19865087
TI  - Acute inflammatory arthritis: interleukin-1 blockade: a magic wand for gout?

PMID- 19865088
TI  - Therapy: what should we do after the failure of a first anti-TNF?

PMID- 19865089
TI  - Osteoarthritis: more evidence for non-pharmacological OA therapy.

PMID- 19865090
TI  - A case of Poncet disease diagnosed with interferon-gamma-release assays.
AB  - BACKGROUND: A 55-year-old, HLA-B27-positive Finnish woman presented with
      migratory, sterile polyarthritis. INVESTIGATIONS: Physical examination, chest
      radiography, serologic testing, microscopy, M. tuberculosis-specific interferon
      gamma enzyme-linked immunospot (ELISPOT) assay, smear and culture of synovial
      fluid for acid-fast bacilli, and PCR. DIAGNOSIS: The patient's assayed blood and
      synovial fluid lymphocytes were reactive, and the numbers of M. tuberculosis
      specific T cells, as determined by ELISPOT, were twofold to sixfold higher in
      synovial fluid than in blood. Cultures for acid-fast bacilli remained negative,
      while PCR specific for DNA of the M. tuberculosis complex was positive in
      synovial fluid cells. These results suggested that the patient had either active
      or latent M. tuberculosis infection. This finding, coupled with the presence of
      polyarthritis, led to a diagnosis of Poncet disease. MANAGEMENT: Standard
      antituberculous therapy consisting of isoniazid, rifampicin and pyrazinamide was
      given for 2 months, followed by isoniazid and rifampicin for 4 months. Inflamed
      joints were treated with methylprednisolone injections. The polyarthritis
      resolved within 4 months of initiating antituberculous therapy.

PMID- 19865091
TI  - Vaccines and autoimmunity.
AB  - Vaccines have been used for over 200 years and are the most effective way of
      preventing the morbidity and mortality associated with infections. Like other
      drugs, vaccines can cause adverse events, but unlike conventional medicines,
      which are prescribed to people who are ill, vaccines are administered to healthy
      individuals, thus increasing the concern over adverse reactions. Most side
      effects attributed to vaccines are mild, acute and transient; however, rare
      reactions such as hypersensitivity, induction of infection, and autoimmunity do
      occur and can be severe and even fatal. The rarity and subacute presentation of
      post-vaccination autoimmune phenomena means that ascertaining causality between
      these events can be difficult. Moreover, the latency period between vaccination
      and autoimmunity ranges from days to years. In this article, on the basis of
      published evidence and our own experience, we discuss the various aspects of the
      causal and temporal interactions between vaccines and autoimmune phenomena, as
      well as the possible mechanisms by which different components of vaccines might
      induce autoimmunity.

PMID- 19865092
TI  - Atorvastatin improves the response to sildenafil in hypercholesterolemic men with
      erectile dysfunction not initially responsive to sildenafil.
AB  - Despite the initial enthusiasm, the significant number of patients in whom
      sildenafil is contraindicated or ineffective is a major challenge to all
      urologists. Our aim was to determine the safety and efficacy of adjunctive
      atorvastatin in restoring normal erectile function in hypercholesterolemic (low
      density lipoprotein (LDL) cholesterol >120 mg per 100 ml) sildenafil
      nonresponders. The study comprised 131 men with ED not responding to sildenafil
      citrate. They were randomized either to 40 mg atorvastatin daily (n=66, group 1)
      or matching placebo (n=65, group 2) for 12 weeks while they were taking on-demand
      100 mg sildenafil. Erectile function was subjectively assessed using the 5-item
      version of the International Index of Erectile Function (IIEF-5) questionnaire
      and response to the global efficacy question (GEQ). Serum biochemical and lipid
      profile (total cholesterol, triglycerides, LDL cholesterol and high-density
      lipoprotein cholesterol) analyses were performed at baseline and repeated at post
      treatment weeks 6 and 12. Compared with the placebo group (59 patients, mean
      age+/-s.d. 61.9+/-6.1, mean years ED 3.9+/-1.8), the atorvastatin group (59
      patients, mean age+/-s.d. 63.9+/-6.9, mean years ED 3.7+/-1.6) had significantly
      greater improvements in all IIEF-5 questions (P=0.01) and GEQ (P=0.001). Subgroup
      analyses did reveal trends in the atorvastatin group to indicate that a change in
      the IIEF-5 score is affected by age, severity of ED and baseline serum levels of
      LDL. Patients with moderate (r=0.28, P=0.01) and severe (r=0.20, P=0.01) ED had
      better positive response rates to adjunctive atorvastatin than patients with mild
      to moderate ED. None of the patients taking atorvastatin achieved a response of 5
      to the IIEF-5 questions and none of the patients regained normal erectile
      function as defined by the IIEF-5 score >21. Subjects experienced a statistically
      significant but modest improvement in erectile function. Further investigation is
      needed to test the usefulness of long-term atorvastatin administration to restore
      erectile function in sildenafil nonresponders.

PMID- 19865093
TI  - Outcomes of early parenteral nutrition for premature infants.
AB  - OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of
      early amino acid (early AA) administration in very low birth weight (VLBW)
      infants. STUDY DESIGN: A pre- and post-intervention study was conducted after
      initiating an early AA administration protocol. Clinical outcomes were collected
      for all VLBW infants admitted on the first day of life for 9 months before
      protocol initiation (standard parenteral nutrition (PN)), and 10 months after
      initiation of early AA. RESULT: In all, 88 infants met study criteria for
      standard PN, and 85 infants for early AA administration. The patient
      characteristics were similar between the groups. There were no differences in
      mortality, the day birth weight was regained, the day enteral feeds started, the
      duration of PN, the day full feeds achieved and weight at 32 weeks post-menstrual
      age. No differences were found for late sepsis, direct hyperbilirubinemia and
      chronic lung disease. Necrotizing enterocolitis (NEC) occurred more frequently in
      the early AA administration group (12 vs 1%, P=0.012). CONCLUSION: Early AA
      administration for VLBW infants was as efficacious as standard therapy, although
      increased NEC in the early AA period may have negatively affected growth and
      nutrition in that period.

PMID- 19865094
TI  - Mutations in the keratin 85 (KRT85/hHb5) gene underlie pure hair and nail
      ectodermal dysplasia.

PMID- 19865095
TI  - AGE-modified collagens I and III induce keratinocyte terminal differentiation
      through AGE receptor CD36: epidermal-dermal interaction in acquired perforating
      dermatosis.
AB  - To clarify the molecular mechanism underlying the transepidermal extrusion of
      dermal collagen in acquired perforating dermatosis (APD) associated with diabetes
      mellitus and renal failure, we studied the interaction between advanced glycation
      end product (AGE)-modified extracellular matrix proteins and keratinocytes (KCs)
      in a cell culture system. The expression of involucrin (INV) and keratin 10 was
      significantly enhanced in normal human KCs grown on AGE-modified collagen I or
      III compared with cells grown on unmodified collagen I or III. Glycated collagens
      I and III preferentially induced the expression of AGE receptor CD36, but not of
      other AGE receptors. KCs induced to terminal differentiation demonstrated
      markedly elevated CD36 expression. Glycated collagen I- and III-induced INV
      expression was partially blocked by the anti-CD36 antibody (Ab). These substrates
      also induced epidermal matrix metalloproteinase 9 (MMP-9) expression. Lesional
      skin from APD patients reacted moderately or strongly with the anti-CD36 Ab as
      well as the anti-MMP-9 Ab in the epidermal cells surrounding the collagenous
      materials being eliminated. These results suggest that exposing KCs to AGE
      modified interstitial collagen (types I and III) by scratching induces terminal
      differentiation of KCs via the AGE receptor (CD36), leading to the upward
      movement of KCs together with glycated collagen.

PMID- 19865096
TI  - IL-18 downregulates collagen production in human dermal fibroblasts via the ERK
      pathway.
AB  - Excessive accumulation of collagen contributes to the fibrotic process. Several
      experimental studies have shown that IFN-gamma is effective in preventing
      fibrogenesis. IL-18, originally identified as an IFN-gamma-inducing factor, is a
      key mediator of inflammation and host defense responses. In this study, we
      investigated the regulatory effect of IL-18 on the expression of type I and III
      collagen genes in dermal fibroblasts. The exposure of human dermal fibroblasts
      (HDFs) to IL-18 resulted in a reduction of collagen gene expression and
      production. Also, IL-18 inhibited the fibrogenic cytokine transforming growth
      factor (TGF)-beta-induced collagen gene expression. Next, to determine the
      molecular mechanism involved in this regulation, we showed that IL-18-regulated
      collagen expression was blocked by small interfering RNA (siRNA)-mediated Ets-1
      knockdown. Furthermore, we showed that IL-18 induced phosphorylation of
      extracellular signal-regulated kinase (ERK) within 10 minutes and that the ERK
      inhibitor PD98059 blocked the inhibitory effect of IL-18. IL-18 also inhibited
      the production of collagen in systemic sclerosis (SSc) dermal fibroblasts. Our
      data indicate that IL-18 downregulates collagen production in HDF directly via
      Ets-1 and the ERK pathway, suggesting that IL-18 may exert antifibrotic
      activities in dermal fibroblasts.

PMID- 19865097
TI  - A comprehensive analysis reveals mutational spectra and common alleles in Chinese
      patients with oculocutaneous albinism.
AB  - Oculocutaneous albinism (OCA) is a heterogeneous recessive disorder with
      hypopigmentation in the skin, hair, and eyes. At least 16 genes have been
      identified as causative genes for human OCA. No comprehensive analysis has been
      conducted to study the spectral distribution of OCA in Chinese patients. We
      screened 127 unrelated and unselected Chinese OCA patients for mutations in the
      TYR, OCA2, TYRP1, SLC45A2, and HPS1 genes. We found that the spectrum of
      mutational genes and alleles of OCA is population specific. OCA1 is the most
      common (70.1% of cases) form of Chinese OCA, whereas OCA2, OCA4, and HPS1 account
      for 10.2%, 12.6%, and 1.6%, respectively. No apparent pathological mutation of
      TYRP1 has been found. Thirty-eight previously unreported mutational alleles were
      identified from these OCA patients and were not found in 100 nonalbinism
      subjects. Of the TYR mutational alleles, 81.1% were clustered on exons 1 and 2.
      Ten common alleles account for 74.6% of the mutational TYR alleles in Chinese
      OCA1 patients. The p.D160H allele accounts for 55.6% of the mutational SLC45A2
      alleles in Chinese OCA4 patients. These results provide useful information for
      the establishment of an optimized strategy of gene diagnosis and genetic
      counseling of Chinese OCA patients.

PMID- 19865098
TI  - ADAM10 is upregulated in melanoma metastasis compared with primary melanoma.
AB  - ADAM10 (a disintegrin and metalloproteinase 10) is involved in the ectodomain
      shedding of various substrates, including adhesion molecules such as L1 cell
      adhesion molecule (L1-CAM) and CD44, which are known to have important roles in
      the development of malignant melanoma. In our study, we characterized the
      expression of ADAM10 in melanoma cells in vitro and in vivo. Immunohistochemical
      analysis on tissue microarrays indicated that ADAM10 expression was significantly
      elevated in melanoma metastasis compared with primary melanomas. In vitro
      downregulation of ADAM10 with specific small interfering RNA (siRNA) resulted in
      a suppression of the anchorage-independent cell growth and reduced the migration
      of melanoma cells. In addition, overexpression of ADAM10 induced the migration of
      melanoma cells. In cell lines from melanoma patients with metastasis, ADAM10 was
      significantly overexpressed, and ADAM10 expression correlated with increased cell
      proliferation. Furthermore, we present evidence that ADAM10 is involved in the
      release of L1-CAM from melanoma cells. It is important that knockdown of cellular
      L1-CAM reduced the migration of melanoma cells and abrogated the chemoresistance
      against cisplatin. In contrast, soluble L1-CAM had no effect on melanoma cell
      migration or cell survival. Taken together, our data demonstrate that ADAM10 and
      L1-CAM have important roles during melanoma progression and both molecules
      represent attractive targets for therapeutical intervention of melanomas.

PMID- 19865100
TI  - Pediatric mastocytosis is a clonal disease associated with D816V and other
      activating c-KIT mutations.
AB  - Adult mastocytosis is an incurable clonal disease associated with c-KIT
      mutations, mostly in exon 17 (D816V). In contrast, pediatric mastocytosis often
      spontaneously regresses and is considered a reactive disease. Previous studies on
      childhood mastocytosis assessed only a few patients and focused primarily on
      codon 816 mutations, with various results. In this study, we analyzed the entire
      c-KIT sequence from cutaneous biopsies of 50 children with mastocytosis (ages 0
      16 years). A mutation of codon 816 (exon 17) was found in 42% of cases, and
      mutations outside exon 17 were observed in 44%. Unexpectedly, half of the
      mutations were located in the fifth Ig loop of c-KIT's extracellular domain,
      which is encoded by exons 8 and 9. All mutations identified in this study were
      somatic and caused a constitutive activation of c-KIT. There was no clear
      phenotype-genotype correlation, no clear relationship between the mutations and
      familial versus spontaneous disease, and no significant change in the relative
      expression of the c-KIT GNNK+ and GNNK isoforms. These findings strongly support
      the idea that, although pediatric mastocytosis can spontaneously regress, it is a
      clonal disease most commonly associated with activating mutations in c-KIT.

PMID- 19865099
TI  - Familial tumoral calcinosis: from characterization of a rare phenotype to the
      pathogenesis of ectopic calcification.
AB  - Familial tumoral calcinosis (FTC) refers to a heterogeneous group of inherited
      disorders characterized by the occurrence of cutaneous and subcutaneous calcified
      masses. Two major forms of the disease are now recognized. Hyperphosphatemic FTC
      has been shown to result from mutations in three genes: fibroblast growth factor
      23 (FGF23), coding for a potent phosphaturic protein, KL encoding Klotho, which
      serves as a co-receptor for FGF23, and GALNT3, which encodes a
      glycosyltransferase responsible for FGF23 O-glycosylation; defective function of
      any one of these three proteins results in hyperphosphatemia and ectopic
      calcification. The second form of the disease is characterized by absence of
      metabolic abnormalities, and is, therefore, termed normophosphatemic FTC. This
      variant was found to be associated with absence of functional SAMD9, a putative
      tumor suppressor and anti-inflammatory protein. The data gathered through the
      study of these rare disorders have recently led to the discovery of novel aspects
      of the pathogenesis of common disorders in humans, underscoring the potential
      concealed within the study of rare diseases.

PMID- 19865101
TI  - Genetic variants of CC chemokine genes in experimental autoimmune
      encephalomyelitis, multiple sclerosis and rheumatoid arthritis.
AB  - Multiple sclerosis (MS) is a complex disorder of the central nervous system,
      causing inflammation, demyelination and axonal damage. A limited number of
      genetic risk factors for MS have been identified, but the etiology of the disease
      remains largely unknown. For the identification of genes regulating
      neuroinflammation we used a rat model of MS, myelin oligodendrocyte glycoprotein
      (MOG)-induced experimental autoimmune encephalomyelitis (EAE), and carried out a
      linkage analysis in an advanced intercross line (AIL). We thereby redefine the
      Eae18b locus to a 0.88 Mb region, including a cluster of chemokine genes.
      Further, we show differential expression of Ccl2, Ccl11 and Ccl11 during EAE in
      rat strains with opposite susceptibility to EAE, regulated by genotype in Eae18b.
      The human homologous genes were tested for association to MS in 3841 cases and
      4046 controls from four Nordic countries. A haplotype in CCL2 and rs3136682 in
      CCL1 show a protective association to MS, whereas a haplotype in CCL13 is disease
      predisposing. In the HLA-DRB1* 15 positive subgroup, we also identified an
      association to a risk haplotype in CCL2, suggesting an influence from the human
      leukocyte antigen (HLA) locus. We further identified association to rheumatoid
      arthritis in CCL2, CCL8 and CCL13, indicating common regulatory mechanisms for
      complex diseases.

PMID- 19865102
TI  - Multiple sclerosis susceptibility alleles in African Americans.
AB  - Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by
      complex genetics and multifaceted gene-environment interactions. Compared to
      whites, African Americans have a lower risk for developing MS, but African
      Americans with MS have a greater risk of disability. These differences between
      African Americans and whites may represent differences in genetic susceptibility
      and/or environmental factors. SNPs from 12 candidate genes have recently been
      identified and validated with MS risk in white populations. We performed a
      replication study using 918 cases and 656 unrelated controls to test whether
      these candidate genes are also associated with MS risk in African Americans. CD6,
      CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in
      the African American data set. EVI5 showed the strongest association outside the
      major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P
      value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A
      seems to be associated with disease progression. None of the tested variants
      showed results that were statistically inconsistent with the effects established
      in whites. The results are consistent with shared disease genetic mechanisms
      among individuals of European and African ancestry.

PMID- 19865103
TI  - Identification of a novel cerebral malaria susceptibility locus (Berr5) on mouse
      chromosome 19.
AB  - Cerebral malaria (CM) is an acute, generally lethal condition characterized by
      high fever, seizures and coma. The genetic component to CM can be investigated in
      mouse models that vary in degree of susceptibility to infection with Plasmodium
      berghei ANKA. Using survival time to measure susceptibility in an informative F2
      cross (n=257), we identified linkage to chromosome 19 (Berr5 (Berghei resistance
      locus 5), LOD=4.69) controlling, in part, the differential response between
      resistant BALB/c and susceptible C57BL/6 progenitors. BALB/c alleles convey
      increased survival through the cerebral phase of infection but have no
      quantitative effect on parasitemia during the later, anemic phase. The Berr5
      locus colocalizes with three other immune loci, including Trl-4 (tuberculosis
      resistance), Tsiq2 (T-cell secretion of IL-4) and Eae19 (experimental allergic
      encephalitis 19), suggesting the possibility of a common genetic effect
      underlying these phenotypes. Potential positional candidates include the family
      of Ifit1-3 (interferon-inducible protein with tetratricopeptide repeats 1-3) and
      Fas.

PMID- 19865104
TI  - Mapping of Char10, a novel malaria susceptibility locus on mouse chromosome 9.
AB  - Resistance to blood-stage malaria in AcB55 and AcB61 is caused by a loss of
      function mutation in pyruvate kinase (Pklr(I90N)). Likewise, pyruvate kinase (PK)
      deficiency in humans is protective against Plasmodium replication in vitro. We
      identified a third AcB strain, AcB62 that also carries the Pklr(I90N) mutation.
      However, AcB62 mice were susceptible to P.chabaudi infection and showed high
      levels of parasite replication (54-62% peak parasitemia). AcB62 mice showed the
      hallmarks of PK deficiency-associated anemia similar to AcB55/61 with
      reticulocytosis, splenic red pulp expansion, tissue iron overload, and increased
      expression of iron metabolism proteins. This suggests that malaria susceptibility
      in AcB62 is not because of absence of PK deficiency-associated pathophysiology.
      To map novel genetic factors affecting malaria susceptibility in AcB62, we
      generated an informative F2 population using AcB62 (Pklr(I90N)) and CBA-Pk(slc)
      (Pklr(G338D)) as progenitors and identified a novel locus on chromosome 9
      (Char10; LOD=7.24) that controls peak parasitemia. A weaker linkage to the Pklr
      region of chromosome 3 (LOD=3.7) was also detected, a finding that may reflect
      the segregation of the two defective Pklr alleles. AcB62 alleles at both loci are
      associated with higher peak parasitemia. These results identify Char10 as a novel
      locus modulating severity of malaria in the context of PK deficiency.

PMID- 19865105
TI  - Modulation of serum uric acid levels by inosine in patients with multiple
      sclerosis does not affect blood pressure.
AB  - The role of uric acid (UA) in human physiology is subject to controversy. Either
      it is an important radical scavenger, a mostly neutral, waste metabolic product
      that may cause gout and kidney stones if elevated, or it is involved in the
      causation of hypertension, vascular and renal diseases. Recently we conducted a
      clinical trial to determine whether raising the serum UA levels through the oral
      administration of inosine is well tolerated and may benefit patients with
      multiple sclerosis. An important aspect of the safety profile is whether raising
      the serum UA levels elevates blood pressure. During the 1-year trial, blood
      pressure and serum UA levels were monitored in 16 patients. Both parameters were
      recorded throughout the trial that included 69 visits by patients at baseline and
      during the placebo phase as well as 138 visits while receiving inosine treatment.
      We have observed that although the serum UA levels increased significantly during
      the inosine treatment phase of the trial, from 4.2+/-0.8 to 7.1+/-1.7 mg per 100
      ml, blood pressure remained unchanged, averaging 123+/-15/78+/-9. Our findings
      indicate that raising the serum UA levels to upper normal physiological levels
      for a period of up to 1-year does not influence blood pressure significantly.

PMID- 19865106
TI  - Clinical effects of eplerenone, a selective aldosterone blocker, in Japanese
      patients with essential hypertension.
AB  - Eplerenone, a selective aldosterone blocker, has become clinically available in
      Japan since 2007. It has been reported that eplerenone has a potential
      antihypertensive effect, with a profile slightly different from that of
      spironolactone, and has fewer adverse reactions, suggesting that it may become a
      first-line treatment for hypertension. However, clinical data on hypertensive
      patients in Japan are lacking for eplerenone. In this study, we explored the
      clinical efficacy of eplerenone when it is added to an angiotensin-converting
      enzyme (ACE) inhibitor or a long-acting calcium channel blocker (CCB) in 68 (31
      males, 37 females) Japanese patients with essential hypertension. After adding 50
      mg of eplerenone to their basal treatment, blood pressure was significantly
      reduced at 4 weeks, and further reduced after 24 weeks of eplerenone treatment.
      Urinary albumin excretion decreased significantly after 24 weeks. There were no
      significant differences in general biochemical test values or electrolytes, but
      fasting serum triglycerides were significantly decreased after eplerenone
      treatment. The serum potassium level showed no significant change during
      treatment. There were no significant correlations between plasma renin activity
      or plasma aldosterone concentration (PAC) before eplerenone treatment and blood
      pressure after eplerenone treatment, showing that the antihypertensive effect of
      eplerenone is not affected by the patient's renin profile or pretreatment PAC
      values. Eplerenone was also effective in hypertensive patients with metabolic
      syndrome. In conclusion, eplerenone, when coadministered with an ACE inhibitor or
      a long-acting CCB, caused an extremely beneficial antihypertensive effect in
      Japanese patients with essential hypertension, without few clinically important
      adverse events.

PMID- 19865107
TI  - Value of retinal examination in hypertensive encephalopathy.
AB  - The presence of grade III or IV hypertensive retinopathy (HRP) is considered to
      distinguish hypertensive urgencies from emergencies. However, case-reports
      suggest that these retinal changes may be lacking in patients with hypertensive
      encephalopathy. To assess the frequency of grade III and IV retinopathy in this
      hypertensive emergency, we conducted a retrospective cohort study. We retrieved
      162 patients with malignant hypertension and 34 patients (17%) fulfilled the
      predefined criteria for hypertensive encephalopathy. Data on retinal examination
      were incomplete for 6 patients (18%), thus leaving 28 patients who were analysed
      for the presence or absence of grade III and IV HRP. In 9 (32%) patients with
      hypertensive encephalopathy, grade III or IV HRP was absent, 11 (39%) patients
      presented with grade III and 8 (29%) patients with grade IV retinopathy. Patients
      without retinal abnormalities were on average 13 years younger (P=0.05), more
      often black (P=0.02) and displayed lower blood pressure (BP) values (P=0.04 for
      systolic and diastolic BP). A substantial proportion of patients with
      hypertensive encephalopathy lack grade III or IV HRP. This suggests that the
      decision to admit these patients should not only rely on the presence of grade
      III and IV retinopathy alone, but should also include a careful neurological
      examination.

PMID- 19865108
TI  - Targeted therapy in T-cell malignancies: dysregulation of the cellular signaling
      pathways.
AB  - T-cell malignancies, mainly known as T-cell acute lymphoblastic leukemia (T-ALL)
      and T-cell non-Hodgkin's lymphoma (T-NHL), are aggressive tumors. Although the
      clinical outcome of the patients has improved dramatically with combination
      chemotherapy, significant challenges remain, including understanding of the
      factors that contribute to the malignant behavior of these tumor cells and
      developing subsequently optimal targeted therapy. Aberrant cell signal
      transduction is generally involved in tumor progression and drug resistance. This
      review describes the pathogenetic role of multiple cellular signaling pathways in
      T-cell malignancies and the potential therapeutic strategies based on the
      modulation of these key signaling networks.

PMID- 19865109
TI  - Myxoma virus targets primary human leukemic stem and progenitor cells while
      sparing normal hematopoietic stem and progenitor cells.

PMID- 19865110
TI  - PML-RARalpha ligand-binding domain deletion mutations associated with reduced
      disease control and outcome after first relapse of APL.

PMID- 19865111
TI  - Similar patterns of chromosome abnormalities in CML occur in addition to the
      Philadelphia chromosome with or without tyrosine kinase inhibitor treatment.

PMID- 19865112
TI  - Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid
      leukemias.

PMID- 19865116
TI  - Darwin and culture.

PMID- 19865117
TI  - Gene therapy deserves a fresh chance.

PMID- 19865118
TI  - Mind the spin.

PMID- 19865125
TI  - Journal club. A biochemist looks at how DNA sequencing can reveal more than just
      sequences.

PMID- 19865131
TI  - African science feels the pinch.

PMID- 19865132
TI  - US physicists propose astrophysics goals.

PMID- 19865133
TI  - Woo Suk Hwang convicted, but not of fraud.

PMID- 19865134
TI  - Dark energy rips cosmos and agencies.

PMID- 19865135
TI  - Ozone protocol squares up to climate.

PMID- 19865136
TI  - University tightens oversight of sensitive research.

PMID- 19865138
TI  - Jury still out on HIV vaccine results.

PMID- 19865139
TI  - Decision-making: Risk school.

PMID- 19865140
TI  - Neuroscience: Shooting pain.

PMID- 19865141
TI  - Weighing up NICE against private health-care schemes.

PMID- 19865143
TI  - Funding on 'Sheriff of Nottingham' model could cut productivity.

PMID- 19865144
TI  - Brainstem tests not adequate to diagnose death in organ donors.

PMID- 19865145
TI  - Global Darwin: Eastern enchantment.

PMID- 19865146
TI  - The day the Internet age began.

PMID- 19865156
TI  - Quantum information: Caught at the finishing line.

PMID- 19865157
TI  - Materials science: Emerging routes to multiferroics.

PMID- 19865158
TI  - Evolutionary biology: Arrhythmia of tempo and mode.

PMID- 19865159
TI  - Astrophysics: Most distant cosmic blast seen.

PMID- 19865160
TI  - Catalysis: Bond control in surface reactions.

PMID- 19865161
TI  - Structural biology: DNA binding shapes up.

PMID- 19865162
TI  - Statistical physics: Swirled by light.

PMID- 19865163
TI  - Volatile accretion history of the terrestrial planets and dynamic implications.
AB  - Accretion left the terrestrial planets depleted in volatile components. Here I
      examine evidence for the hypothesis that the Moon and the Earth were essentially
      dry immediately after the formation of the Moon-by a giant impact on the proto
      Earth-and only much later gained volatiles through accretion of wet material
      delivered from beyond the asteroid belt. This view is supported by U-Pb and I-Xe
      chronologies, which show that water delivery peaked approximately 100 million
      years after the isolation of the Solar System. Introduction of water into the
      terrestrial mantle triggered plate tectonics, which may have been crucial for the
      emergence of life. This mechanism may also have worked for the young Venus, but
      seems to have failed for Mars.

PMID- 19865164
TI  - The role of DNA shape in protein-DNA recognition.
AB  - The recognition of specific DNA sequences by proteins is thought to depend on two
      types of mechanism: one that involves the formation of hydrogen bonds with
      specific bases, primarily in the major groove, and one involving sequence
      dependent deformations of the DNA helix. By comprehensively analysing the three
      dimensional structures of protein-DNA complexes, here we show that the binding of
      arginine residues to narrow minor grooves is a widely used mode for protein-DNA
      recognition. This readout mechanism exploits the phenomenon that narrow minor
      grooves strongly enhance the negative electrostatic potential of the DNA. The
      nucleosome core particle offers a prominent example of this effect. Minor-groove
      narrowing is often associated with the presence of A-tracts, AT-rich sequences
      that exclude the flexible TpA step. These findings indicate that the ability to
      detect local variations in DNA shape and electrostatic potential is a general
      mechanism that enables proteins to use information in the minor groove, which
      otherwise offers few opportunities for the formation of base-specific hydrogen
      bonds, to achieve DNA-binding specificity.

PMID- 19865165
TI  - A gamma-ray burst at a redshift of z approximately 8.2.
AB  - Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions
      of certain massive stars, and some are bright enough that they should be
      observable out to redshifts of z > 20 using current technology. Hitherto, the
      highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting
      galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2,
      implying that massive stars were being produced and dying as GRBs approximately
      630 Myr after the Big Bang. The burst also pinpoints the location of its host
      galaxy.

PMID- 19865166
TI  - GRB 090423 at a redshift of z approximately 8.1.
AB  - Gamma-ray bursts (GRBs) are produced by rare types of massive stellar explosion.
      Their rapidly fading afterglows are often bright enough at optical wavelengths
      that they are detectable at cosmological distances. Hitherto, the highest known
      redshift for a GRB was z = 6.7 (ref. 1), for GRB 080913, and for a galaxy was z =
      6.96 (ref. 2). Here we report observations of GRB 090423 and the near-infrared
      spectroscopic measurement of its redshift, z = 8.1(-0.3)(+0.1). This burst
      happened when the Universe was only about 4 per cent of its current age. Its
      properties are similar to those of GRBs observed at low/intermediate redshifts,
      suggesting that the mechanisms and progenitors that gave rise to this burst about
      600,000,000 years after the Big Bang are not markedly different from those
      producing GRBs about 10,000,000,000 years later.

PMID- 19865167
TI  - Acceleration of neutral atoms in strong short-pulse laser fields.
AB  - A charged particle exposed to an oscillating electric field experiences a force
      proportional to the cycle-averaged intensity gradient. This so-called
      ponderomotive force plays a major part in a variety of physical situations such
      as Paul traps for charged particles, electron diffraction in strong (standing)
      laser fields (the Kapitza-Dirac effect) and laser-based particle acceleration.
      Comparably weak forces on neutral atoms in inhomogeneous light fields may arise
      from the dynamical polarization of an atom; these are physically similar to the
      cycle-averaged forces. Here we observe previously unconsidered extremely strong
      kinematic forces on neutral atoms in short-pulse laser fields. We identify the
      ponderomotive force on electrons as the driving mechanism, leading to ultrastrong
      acceleration of neutral atoms with a magnitude as high as approximately 10(14)
      times the Earth's gravitational acceleration, g. To our knowledge, this is by far
      the highest observed acceleration on neutral atoms in external fields and may
      lead to new applications in both fundamental and applied physics.

PMID- 19865168
TI  - Preserving electron spin coherence in solids by optimal dynamical decoupling.
AB  - To exploit the quantum coherence of electron spins in solids in future
      technologies such as quantum computing, it is first vital to overcome the problem
      of spin decoherence due to their coupling to the noisy environment. Dynamical
      decoupling, which uses stroboscopic spin flips to give an average coupling to the
      environment that is effectively zero, is a particularly promising strategy for
      combating decoherence because it can be naturally integrated with other desired
      functionalities, such as quantum gates. Errors are inevitably introduced in each
      spin flip, so it is desirable to minimize the number of control pulses used to
      realize dynamical decoupling having a given level of precision. Such optimal
      dynamical decoupling sequences have recently been explored. The experimental
      realization of optimal dynamical decoupling in solid-state systems, however,
      remains elusive. Here we use pulsed electron paramagnetic resonance to
      demonstrate experimentally optimal dynamical decoupling for preserving electron
      spin coherence in irradiated malonic acid crystals at temperatures from 50 K to
      room temperature. Using a seven-pulse optimal dynamical decoupling sequence, we
      prolonged the spin coherence time to about 30 mus; it would otherwise be about
      0.04 mus without control or 6.2 mus under one-pulse control. By comparing
      experiments with microscopic theories, we have identified the relevant electron
      spin decoherence mechanisms in the solid. Optimal dynamical decoupling may be
      applied to other solid-state systems, such as diamonds with nitrogen-vacancy
      centres, and so lay the foundation for quantum coherence control of spins in
      solids at room temperature.

PMID- 19865169
TI  - A dearth of intermediate melts at subduction zone volcanoes and the petrogenesis
      of arc andesites.
AB  - Andesites represent a large proportion of the magmas erupted at continental arc
      volcanoes and are regarded as a major component in the formation of continental
      crust. Andesite petrogenesis is therefore fundamental in terms of both volcanic
      hazard and differentiation of the Earth. Andesites typically contain a
      significant proportion of crystals showing disequilibrium petrographic
      characteristics indicative of mixing or mingling between silicic and mafic
      magmas, which fuels a long-standing debate regarding the significance of these
      processes in andesite petrogenesis and ultimately questions the abundance of true
      liquids with andesitic composition. Central to this debate is the distinction
      between liquids (or melts) and magmas, mixtures of liquids with crystals, which
      may or may not be co-genetic. With this distinction comes the realization that
      bulk-rock chemical analyses of petrologically complex andesites can lead to a
      blurred picture of the fundamental processes behind arc magmatism. Here we
      present an alternative view of andesite petrogenesis, based on a review of
      quenched glassy melt inclusions trapped in phenocrysts, whole-rock chemistry, and
      high-pressure and high-temperature experiments. We argue that true liquids of
      intermediate composition (59 to 66 wt% SiO(2)) are far less common in the sub
      volcanic reservoirs of arc volcanoes than is suggested by the abundance of
      erupted magma within this compositional range. Effective mingling within upper
      crustal magmatic reservoirs obscures a compositional bimodality of melts
      ascending from the lower crust, and masks the fundamental role of silicic melts
      (>/=66 wt% SiO(2)) beneath intermediate arc volcanoes. This alternative view
      resolves several puzzling aspects of arc volcanism and provides important clues
      to the integration of plutonic and volcanic records.

PMID- 19865170
TI  - Visual but not trigeminal mediation of magnetic compass information in a
      migratory bird.
AB  - Magnetic compass information has a key role in bird orientation, but the
      physiological mechanisms enabling birds to sense the Earth's magnetic field
      remain one of the unresolved mysteries in biology. Two biophysical mechanisms
      have become established as the most promising magnetodetection candidates. The
      iron-mineral-based hypothesis suggests that magnetic information is detected by
      magnetoreceptors in the upper beak and transmitted through the ophthalmic branch
      of the trigeminal nerve to the brain. The light-dependent hypothesis suggests
      that magnetic field direction is sensed by radical pair-forming photopigments in
      the eyes and that this visual signal is processed in cluster N, a specialized,
      night-time active, light-processing forebrain region. Here we report that
      European robins with bilateral lesions of cluster N are unable to show oriented
      magnetic-compass-guided behaviour but are able to perform sun compass and star
      compass orientation behaviour. In contrast, bilateral section of the ophthalmic
      branch of the trigeminal nerve in European robins did not influence the birds'
      ability to use their magnetic compass for orientation. These data show that
      cluster N is required for magnetic compass orientation in this species and
      indicate that it may be specifically involved in processing of magnetic compass
      information. Furthermore, the data strongly suggest that a vision-mediated
      mechanism underlies the magnetic compass in this migratory songbird, and that the
      putative iron-mineral-based receptors in the upper beak connected to the brain by
      the trigeminal nerve are neither necessary nor sufficient for magnetic compass
      orientation in European robins.

PMID- 19865171
TI  - Regulation of cortical microcircuits by unitary GABA-mediated volume
      transmission.
AB  - GABA (gamma-aminobutyric acid) is predominantly released by local interneurons in
      the cerebral cortex to particular subcellular domains of the target cells. This
      suggests that compartmentalized, synapse-specific action of GABA is required in
      cortical networks for phasic inhibition. However, GABA released at the synaptic
      cleft diffuses to receptors outside the postsynaptic density and thus tonically
      activates extrasynaptic GABA(A) and GABA(B) receptors, which include subtypes of
      both receptor families especially sensitive to low concentrations of GABA. The
      synaptic and extrasynaptic action of GABA corroborates the idea that neurons of
      the brain use synaptic (or wiring) transmission and non-synaptic (or volume)
      transmission for communication. However, re-uptake mechanisms restrict the
      spatial extent of extrasynaptic GABA-mediated effects, and it has been proposed
      that the concerted action of several presynaptic interneurons, the sustained
      firing of individual cells or an increase in release-site density is required to
      reach ambient GABA levels sufficient to activate extrasynaptic receptors. Here we
      show that individual neurogliaform cells release enough GABA for volume
      transmission within the axonal cloud and, thus, that neurogliaform cells do not
      require synapses to produce inhibitory responses in the overwhelming majority of
      nearby neurons. Neurogliaform cells suppress connections between other neurons
      acting on presynaptic terminals that do not receive synapses at all in the
      cerebral cortex. They also reach extrasynaptic, delta-subunit-containing GABA(A)
      (GABA(Adelta)) receptors responsible for tonic inhibition. We show that
      GABA(Adelta) receptors are localized to neurogliaform cells preferentially among
      cortical interneurons. Neurosteroids, which are modulators of GABA(Adelta)
      receptors, alter unitary GABA-mediated effects between neurogliaform cells. In
      contrast to the specifically placed synapses formed by other interneurons, the
      output of neurosteroid-sensitive neurogliaform cells represents the ultimate form
      of the lack of spatial specificity in GABA-mediated systems, leading to long
      lasting network hyperpolarization combined with widespread suppression of
      communication in the local circuit.

PMID- 19865172
TI  - Regulation of inflammatory responses by gut microbiota and chemoattractant
      receptor GPR43.
AB  - The immune system responds to pathogens by a variety of pattern recognition
      molecules such as the Toll-like receptors (TLRs), which promote recognition of
      dangerous foreign pathogens. However, recent evidence indicates that normal
      intestinal microbiota might also positively influence immune responses, and
      protect against the development of inflammatory diseases. One of these elements
      may be short-chain fatty acids (SCFAs), which are produced by fermentation of
      dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and
      other colitic diseases is a change in 'healthy' microbiota such as
      Bifidobacterium and Bacteriodes, and a concurrent reduction in SCFAs. Moreover,
      increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically
      beneficial in the treatment of colitis. SCFAs bind the G-protein-coupled receptor
      43 (GPR43, also known as FFAR2), and here we show that SCFA-GPR43 interactions
      profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was
      necessary for the normal resolution of certain inflammatory responses, because
      GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving inflammation
      in models of colitis, arthritis and asthma. This seemed to relate to increased
      production of inflammatory mediators by Gpr43(-/-) immune cells, and increased
      immune cell recruitment. Germ-free mice, which are devoid of bacteria and express
      little or no SCFAs, showed a similar dysregulation of certain inflammatory
      responses. GPR43 binding of SCFAs potentially provides a molecular link between
      diet, gastrointestinal bacterial metabolism, and immune and inflammatory
      responses.

PMID- 19865173
TI  - Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis.
AB  - A growing body of evidence indicates that resolution of acute inflammation is an
      active process. Resolvins are a new family of lipid mediators enzymatically
      generated within resolution networks that possess unique and specific functions
      to orchestrate catabasis, the phase in which disease declines. Resolvin D2 (RvD2)
      was originally identified in resolving exudates, yet its individual contribution
      in resolution remained to be elucidated. Here, we establish RvD2's potent
      stereoselective actions in reducing excessive neutrophil trafficking to
      inflammatory loci. RvD2 decreased leukocyte-endothelial interactions in vivo by
      endothelial-dependent nitric oxide production, and by direct modulation of
      leukocyte adhesion receptor expression. In mice with microbial sepsis initiated
      by caecal ligation and puncture, RvD2 sharply decreased both local and systemic
      bacterial burden, excessive cytokine production and neutrophil recruitment, while
      increasing peritoneal mononuclear cells and macrophage phagocytosis. These multi
      level pro-resolving actions of RvD2 translate to increased survival from sepsis
      induced by caecal ligation and puncture and surgery. Together, these results
      identify RvD2 as a potent endogenous regulator of excessive inflammatory
      responses that acts via multiple cellular targets to stimulate resolution and
      preserve immune vigilance.

PMID- 19865174
TI  - Exploitation of binding energy for catalysis and design.
AB  - Enzymes use substrate-binding energy both to promote ground-state association and
      to stabilize the reaction transition state selectively. The monomeric homing
      endonuclease I-AniI cleaves with high sequence specificity in the centre of a 20
      base-pair (bp) DNA target site, with the amino (N)-terminal domain of the enzyme
      making extensive binding interactions with the left (-) side of the target site
      and the similarly structured carboxy (C)-terminal domain interacting with the
      right (+) side. Here we show that, despite the approximate twofold symmetry of
      the enzyme-DNA complex, there is almost complete segregation of interactions
      responsible for substrate binding to the (-) side of the interface and
      interactions responsible for transition-state stabilization to the (+) side.
      Although single base-pair substitutions throughout the entire DNA target site
      reduce catalytic efficiency, mutations in the (-) DNA half-site almost
      exclusively increase the dissociation constant (K(D)) and the Michaelis constant
      under single-turnover conditions (K(M)*), and those in the (+) half-site
      primarily decrease the turnover number (k(cat)*). The reduction of activity
      produced by mutations on the (-) side, but not mutations on the (+) side, can be
      suppressed by tethering the substrate to the endonuclease displayed on the
      surface of yeast. This dramatic asymmetry in the use of enzyme-substrate binding
      energy for catalysis has direct relevance to the redesign of endonucleases to
      cleave genomic target sites for gene therapy and other applications.
      Computationally redesigned enzymes that achieve new specificities on the (-) side
      do so by modulating K(M)*, whereas redesigns with altered specificities on the
      (+) side modulate k(cat)*. Our results illustrate how classical enzymology and
      modern protein design can each inform the other.

PMID- 19865177
TI  - Proliferating NK cells in response to IL-15 do not upregulate surface B220 in
      vivo.

PMID- 19865176
TI  - DNA prime-protein boost increased the titer, avidity and persistence of anti
      Abeta antibodies in wild-type mice.
AB  - Recently, we reported that a DNA vaccine, composed of three copies of a self B
      cell epitope of amyloid-beta (Abeta(42)) and the foreign T-cell epitope, Pan DR
      epitope (PADRE), generated strong anti-Abeta immune responses in wild-type and
      amyloid precursor protein transgenic animals. Although DNA vaccines have several
      advantages over peptide-protein vaccines, they induce lower immune responses in
      large animals and humans compared with those in mice. The focus of this study was
      to further enhance anti-Abeta(11) immune responses by developing an improved DNA
      vaccination protocol of the prime-boost regimen, in which the priming step would
      use DNA and the boosting step would use recombinant protein. Accordingly, we
      generated DNA and recombinant protein-based epitope vaccines and showed that
      priming with DNA followed by boosting with a homologous recombinant protein
      vaccine significantly increases the anti-Abeta antibody responses and do not
      change the immunoglobulin G1 (IgG1) profile of humoral immune responses.
      Furthermore, the antibodies generated by this prime-boost regimen were long
      lasting and possessed a higher avidity for binding with an Abeta(42) peptide.
      Thus, we showed that a heterologous prime-boost regimen could be an effective
      protocol for developing a potent Alzheimer's disease (AD) vaccine.

PMID- 19865179
TI  - SLAM-enriched hematopoietic stem cells maintain long-term repopulating capacity
      after lentiviral transduction using an abbreviated protocol.
AB  - Gene transfer to long-term repopulating hematopoietic stem cells (HSCs) using
      integrating viral vectors is an important goal in gene therapy. The SLAM
      (signaling lymphocyte activation molecule)-family receptors have recently been
      used for the isolation of highly enriched murine HSCs. This HSC enrichment
      protocol is relatively simple, and results in an HSC population with comparable
      repopulating capacity to c-kit(+)lin(-)Sca-1(+) (KSL) HSCs. The capacity to
      withstand genetic manipulation and, most importantly, to maintain long-term
      repopulating capacity of SLAM-enriched HSC populations has not been reported. In
      this study, SLAM-enriched HSCs were assessed for transduction efficiency and in
      vivo long-term repopulating capacity after lentiviral transduction using an
      abbreviated transduction protocol and KSL-enriched HSCs as a reference
      population. SLAM- and KSL-enriched HSCs were efficiently transduced by lentiviral
      vector using a simple protocol that involves minimal in vitro manipulation and no
      pre-stimulation. SLAM-HSCs are at least equal to KSL-HSCs with respect to
      efficiency of transduction and maintenance of long-term repopulating capacity.
      Although there was a reduction in repopulating capacity related to enrichment and
      culture manipulations relative to freshly isolated bone marrow (BM) cells, no
      detrimental effects were identified on long-term competitive capacity related to
      transduction, as transduced cells maintained stable levels of chimerism in
      competition with non-transduced cells and freshly isolated BM cells. These
      results support the SLAM-HSC enrichment protocol as a simple and efficient method
      for HSC enrichment for gene transfer studies.

PMID- 19865178
TI  - Extending the transposable payload limit of Sleeping Beauty (SB) using the Herpes
      Simplex Virus (HSV)/SB amplicon-vector platform.
AB  - The ability of a viral vector to safely deliver and stably integrate large
      transgene units (transgenons), which not only include one or several therapeutic
      genes, but also requisite native transcriptional regulatory elements, would be of
      significant benefit for diseases presently refractory to available technologies.
      The herpes simplex virus type-1 (HSV-1) amplicon vector has the largest known
      payload capacity of approximately 130 kb, but its episomal maintenance within the
      transduced cell nucleus and induction of host cell silencing mechanisms limits
      the duration of the delivered therapeutic gene(s). Our laboratory developed an
      integration-competent version of the HSV-1 amplicon by adaptation of the Sleeping
      Beauty (SB) transposon system, which significantly extends transgene expression
      in vivo. The maximum size limit of the amplicon-vectored transposable element
      remains unknown, but previously published plasmid-centric studies have
      established that DNA segments longer than 6-kb are inefficiently transposed.
      Here, we compared the transposition efficiency of SB transposase in the context
      of both the HSV amplicon vector as well as the HSV amplicon plasmid harboring 7
      and 12-kb transposable reporter transgene units. Our results indicate that the
      transposition efficiency of the 12-kb transposable unit via SB transposase was
      significantly reduced as compared with the 7-kb transposable unit when the
      plasmid version of the HSV amplicon was used. However, the packaged HSV amplicon
      vector form provided a more amenable platform from which the 12-kb transposable
      unit was mobilized at efficiency similar to that of the 7-kb transposable unit
      via the SB transposase. Overall, our results indicate that SB is competent in
      stably integrating transgenon units of at least 12 kb in size within the human
      genome upon delivery of the platform via HSV amplicons.

PMID- 19865180
TI  - DsAAV8-mediated expression of glucagon-like peptide-1 in pancreatic beta-cells
      ameliorates streptozotocin-induced diabetes.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone that performs a wide array
      of well-characterized antidiabetic actions, including stimulation of glucose
      dependent insulin secretion, upregulation of insulin gene expression and
      improvements in beta-cell survival. GLP-1-receptor agonists have been developed
      for treatment of diabetes; however, the short biological half-lives of these
      peptide-based therapeutics requires that frequent injections be administered to
      maintain sufficient circulating levels. Thus, novel methods of delivering GLP-1
      remain an important avenue of active research. It has recently been demonstrated
      that self-complimentary, double-stranded, adeno-associated virus serotype-8
      (DsAAV8) can efficiently transduce pancreatic beta-cells in vivo, resulting in
      long-term transgene expression. In this study, we engineered a DsAAV8 vector
      containing a GLP-1 transgene driven by the mouse insulin-II promoter (MIP).
      Biological activity of the GLP-1 produced from this transgene was assessed using
      a luciferase-based bioassay. DsAAV8-MIP-GLP-1 was delivered via intraperitoneal
      injection and beta-cell damage induced by multiple low dose streptozotocin (STZ)
      administration. Glucose tolerance was assessed following intraperitoneal glucose
      injections and beta-cell proliferation measured by PCNA expression. Expression of
      GLP-1 in Min6 beta-cells resulted in glucose-dependent secretion of biologically
      active GLP-1. Intraperitoneal delivery of DsAAV8-MIP-GLP-1 to mice led to
      localized GLP-1 expression in beta-cells and protection against development of
      diabetes induced by multiple low-dose STZ administration. This protection was
      associated with significant increase in beta-cell proliferation. Results from
      this study indicate that expression and secretion of GLP-1 from beta-cells in
      vivo via DsAAV8 represents a novel therapeutic strategy for treatment of
      diabetes.

PMID- 19865181
TI  - A new PG13-based packaging cell line for stable production of clinical-grade self
      inactivating gamma-retroviral vectors using targeted integration.
AB  - The clinical application of self-inactivating (SIN) retroviral vectors has been
      hampered by the lack of reliable and efficient vector production technologies. To
      enable production of SIN gamma-retroviral vectors from stable producer clones, a
      new PG13-based packaging cell, known as PG368, was developed. Viral vector
      expression constructs can be reliably inserted at a predefined genomic locus of
      PG368 packaging cells by an Flp-recombinase-mediated targeted cassette exchange
      (RMCE) reaction. A new, carefully designed vector-targeting construct, pEMTAR-1,
      eliminated the co-packaging of the selectable marker gene used for the
      identification of successful recombination at the predefined genomic locus and
      thus, improved the safety of the production system. Selected clones produced
      vector supernatants at consistent titers. The targeted insertion of
      therapeutically relevant SIN vectors for chronic granulomatous disease and X
      linked severe combined immunodeficiency into PG368 cells results in stable titers
      within the range necessary for clinical application. The production of retroviral
      SIN vectors from stable clinical-grade producer cells is feasible and will
      contribute to the safe production and application of SIN gamma-retroviral vectors
      for clinical trials.

PMID- 19865182
TI  - Chemoprotection of human hematopoietic stem cells by simultaneous lentiviral
      overexpression of multidrug resistance 1 and O(6)-methylguanine-DNA
      methyltransferase(P140K).
AB  - Myelotoxicity is a dose-limiting effect of many chemotherapeutic regimens. Thus,
      there is great interest in protecting human hematopoietic stem cells by the
      transfer of drug resistance genes. The main focus of this study was the
      simultaneous overexpression of multidrug resistance 1 (MDR1) and the O(6)
      benzylguanine (O(6)-BG)-resistant mutant MGMT(P140K) (O(6)-methylguanine-DNA
      methyltransferase) with a bicistronic lentiviral vector (HR'SIN-MDR1-IRES
      MGMT(P140K)), with regard to the capability to convey chemoprotection in the
      leukemia cell line, HL60, and human hematopoietic stem cells (CD34(+)).
      Combination therapy with O(6)-BG/1-(2-chloroethyl)-3-(4-amino-2-methylpyrimidine
      5-yl)methyl-1-nitrosourea) (ACNU) plus paclitaxel showed a significant survival
      advantage of HL60 cells transduced with this combination vector. In CD34(+)
      cells, monotherapy with O(6)-BG/temozolomide (TMZ) resulted in an increased
      percentage of MGMT-positive cells (vs untreated cells) after transduction with
      HR'SIN-MDR1-IRES-MGMT(P140K) (28.3%). For combination therapy with O(6)
      BG/temozolomide plus paclitaxel the increase was higher with the combination
      vector (52.8%) than with a vector expressing MGMT(P140K) solely (29.1%). With
      regard to MDR1-positive cells the protective effect of the combination vector
      (88.5%) was comparable to the single vector HR'SIN-MDR1 (90.0%) for monotherapy
      with paclitaxel and superior for combination therapy with O(6)-BG/temozolomide
      plus paclitaxel (84.6 vs 69.7%). In conclusion, the combination vector presents
      simultaneous protective effects of two drug-resistance genes, offering an
      opportunity to increase the cancer therapeutic index.

PMID- 19865184
TI  - Bacterial communities of disease vectors sampled across time, space, and species.
AB  - A common strategy of pathogenic bacteria is to form close associations with
      parasitic insects that feed on animals and to use these insects as vectors for
      their own transmission. Pathogens interact closely with other coexisting bacteria
      within the insect, and interactions between co-occurring bacteria may influence
      the vector competency of the parasite. Interactions between particular lineages
      can be explored through measures of alpha-diversity. Furthermore, general
      patterns of bacterial community assembly can be explored through measures of beta
      diversity. Here, we use pyrosequencing (n=115,924 16S rRNA gene sequences) to
      describe the bacterial communities of 230 prairie dog fleas sampled across space
      and time. We use these communinty characterizations to assess interactions
      between dominant community members and to explore general patterns of bacterial
      community assembly in fleas. An analysis of co-occurrence patterns suggests non
      neutral negative interactions between dominant community members (P<0.001).
      Furthermore, bacterial communities of fleas shift dramatically across years
      (phylotype-based: R=0.829, P<0.001; phylogenetic-based: R=0.612-0.753, P<0.001),
      but they also significantly differ across space (phylotype-based: R=0.418,
      P<0.001; phylogenetic-based: R=0.290-0.328, P<0.001) and between flea species
      (phylotype-based: R=0.160, P=0.011; phylogenetic-based: not significant).
      Collectively, our results show that flea-associated bacterial communities are not
      random assemblages; rather, an individual flea's bacterial community is governed
      by interactions between bacterial lineages and by the flea's place in space and
      time.

PMID- 19865186
TI  - Simultaneous determination of two or more nonlinear refractive constants by z
      scan measurement.

PMID- 19865185
TI  - Linking environmental heterogeneity and reproductive success at single-cell
      resolution.
AB  - Individual-based microbial ecology (IBME) is a developing field of study in need
      of experimental tools to quantify the individual experience and performance of
      microorganisms in their natural habitats. We describe here the conception and
      application of a single-cell bioreporter approach with broad utility in IBME. It
      is based on the dilution of stable green fluorescent protein (GFP) in dividing
      bacteria. In the absence of de novo synthesis, GFP fluorescence of a daughter
      cell approximates half of that of its mother, from which follows that the
      fluorescence of a progeny cell is a quantitative measure for the reproductive
      success of its ancestor. To test this concept, we exposed GFP-filled bacteria to
      different degrees of environmental heterogeneity and assessed how this affected
      individual cells by the analysis of GFP content in their progeny. Reporter
      bacteria growing in rich medium in a shaking flask showed no variation in
      reproductive success, confirming that life in a broth is experienced much the
      same from one bacterium to the next. In contrast, when reporter bacteria were
      released onto plant leaf surfaces, representing a microscopically heterogeneous
      environment, clear intrapopulation differences in reproductive success were
      observed. Such variation suggests that individual cells in the founding
      population experienced different growth-permitting conditions, resulting in
      unequal contributions of individual bacteria to future offspring and population
      sizes. Being able to assess population changes bottom-up rather than top-down,
      the bioreporter offers opportunities to quantify single-cell competitive and
      facilitative interactions, assess the role of chance events in individual
      survivorship and reveal causes that underlie individual-based environmental
      heterogeneity.

PMID- 19865187
TI  - Thermally stable and large second-order nonlinearity in poled silica films doped
      with Disperse Red 1 in high concentration.

PMID- 19865188
TI  - Suppression of third-order dispersion radiation in solid-state soliton lasers.

PMID- 19865189
TI  - Inhibited light-induced absorption in KNbO3.

PMID- 19865190
TI  - Anomalous-dispersion phase-matched second-harmonic generation in a polymer
      waveguide.

PMID- 19865191
TI  - Surface-strain effects on photorefractive gratings.

PMID- 19865192
TI  - Estimation of nonlinear refractive index in various silica-based glasses for
      optical fibers.

PMID- 19865193
TI  - Interaction of one-dimensional bright solitary waves in quadratic media.

PMID- 19865183
TI  - Interactions between gut microbiota, host genetics and diet relevant to
      development of metabolic syndromes in mice.
AB  - Both genetic variations and diet-disrupted gut microbiota can predispose animals
      to metabolic syndromes (MS). This study assessed the relative contributions of
      host genetics and diet in shaping the gut microbiota and modulating MS-relevant
      phenotypes in mice. Together with its wild-type (Wt) counterpart, the Apoa-I
      knockout mouse, which has impaired glucose tolerance (IGT) and increased body
      fat, was fed a high-fat diet (HFD) or normal chow (NC) diet for 25 weeks. DNA
      fingerprinting and bar-coded pyrosequencing of 16S rRNA genes were used to
      profile gut microbiota structures and to identify the key population changes
      relevant to MS development by Partial Least Square Discriminate Analysis. Diet
      changes explained 57% of the total structural variation in gut microbiota,
      whereas genetic mutation accounted for no more than 12%. All three groups with
      IGT had significantly different gut microbiota relative to healthy Wt/NC-fed
      animals. In all, 65 species-level phylotypes were identified as key members with
      differential responses to changes in diet, genotype and MS phenotype. Most
      notably, gut barrier-protecting Bifidobacterium spp. were nearly absent in all
      animals on HFD, regardless of genotype. Sulphate-reducing, endotoxin-producing
      bacteria of the family, Desulfovibrionaceae, were enhanced in all animals with
      IGT, most significantly in the Wt/HFD group, which had the highest calorie intake
      and the most serious MS phenotypes. Thus, diet has a dominating role in shaping
      gut microbiota and changes of some key populations may transform the gut
      microbiota of Wt animals into a pathogen-like entity relevant to development of
      MS, despite a complete host genome.

PMID- 19865194
TI  - Dual-frequency wall solitary waves for nonreturn-to-zero signal transmission in W
      type single-mode fibers.

PMID- 19865195
TI  - Dynamic transmission properties of a nonlinear fiber ring resonator.

PMID- 19865196
TI  - Analytical theory of guiding-center nonreturn-to-zero and return-to-zero signal
      transmission in normally dispersive nonlinear optical fibers.

PMID- 19865197
TI  - Surface-normal cascaded planar interconnection with easy alignment.

PMID- 19865199
TI  - Miniature integrated-optical wavelength analyzer chip.

PMID- 19865198
TI  - Launching of guided waves in a photorefractive polymer by two-beam coupling.

PMID- 19865200
TI  - Widely tunable femtosecond neodymium fiber laser.

PMID- 19865201
TI  - Single-mode KTiOPO4 optical parametric oscillator.

PMID- 19865202
TI  - Generation of 3-4- mu m femtosecond pulses from a synchronously pumped,
      critically phase-matched KTiOPO4 optical parametric oscillator.

PMID- 19865203
TI  - Diode-pumped Cr:LiSAF all-solid-state femtosecond oscillator and regenerative
      amplifier.

PMID- 19865204
TI  - Self-induced channeling of subpicosecond optical pulses in broad-area bulk
      semiconductor amplifiers.

PMID- 19865206
TI  - Incoherent-erasure joint-transform correlator.

PMID- 19865205
TI  - Nonequilibrium and many-body Coulomb effects in the relaxation oscillation of a
      semiconductor laser.

PMID- 19865207
TI  - Transmission of 1-Gbit / s data patterns through smart pixels by use of
      picosecond laser pulses.

PMID- 19865208
TI  - Optical-radar imaging of scale models for studies in asteroid astronomy.

PMID- 19865209
TI  - Sub-100- mu m depth-resolved holographic imaging through scattering media in the
      near infrared.

PMID- 19865210
TI  - Effect of weak prepulses on collisional x-ray laser plasmas.

PMID- 19865212
TI  - Measurement of the group delay of laser mirrors by a Fabry-Perot interferometer.

PMID- 19865211
TI  - Cross-talk noise reduction in volume holographic storage with an extended
      recording reference.

PMID- 19865213
TI  - Two-dimensional soot-particle sizing by time-resolved laser-induced
      incandescence.

PMID- 19865214
TI  - Dual-mode fiber-optic interferometer: a novel design.

PMID- 19865215
TI  - Polarizing holographic beam splitter on a photoresist.

PMID- 19865216
TI  - High signal-to-noise ratio birefringence-compensated optical delay line based on
      a noise-reduction scheme.

PMID- 19865217
TI  - Holographic first-arriving-light signal-to-noise ratio enhancement by
      differential holography.

PMID- 19865218
TI  - Scattering from fractally corrugated surfaces: an exact approach.

PMID- 19865219
TI  - Derivation of weighting coefficients for multiplexed phase-diffractive elements.

PMID- 19865220
TI  - Relations between spontaneously occurring beams in bismuth silicon oxide with two
      frequency-detuned pump beams.

PMID- 19865221
TI  - Nonlinear dispersion effects in a broadband Raman amplifier.

PMID- 19865222
TI  - Noise in chi ((3)) and photorefractive amplifiers.

PMID- 19865223
TI  - Determination of absolute two-photon excitation cross sections by in situ second
      order autocorrelation.

PMID- 19865224
TI  - 49 mW of cw blue light generated by first-order quasi-phase-matched frequency
      doubling of a diode-pumped 946-nm Nd:YAG laser.

PMID- 19865225
TI  - Vibrational dynamic of the Raman-active mode in barium nitrate crystal.

PMID- 19865226
TI  - All-fiber sliding-frequency Er (3+) / Yb (3+) soliton laser.

PMID- 19865227
TI  - Room-temperature 50-mJ / pulse side-diode-pumped Yb:YAG laser.

PMID- 19865228
TI  - Nonconfocal unstable resonator for solid-state dye lasers based on a gradient
      reflectivity mirror.

PMID- 19865229
TI  - Full polarization chaos in a pump-polarization modulated isotropic cavity laser.

PMID- 19865230
TI  - Two-photon-pumped cavity lasing in a dye-solution-filled hollow-fiber system.

PMID- 19865231
TI  - Determinism and stochasticity of power-dropout events in semiconductor lasers
      with optical feedback.

PMID- 19865232
TI  - Duration-tunable 0.2-20-ps 10-GHz source of transform-limited optical pulses
      based on an electroabsorption modulator.

PMID- 19865234
TI  - Multichannel optical correlator based on a mutually incoherent microlaser array.

PMID- 19865233
TI  - Femtosecond Yb:YAG laser using semiconductor saturable absorbers.

PMID- 19865235
TI  - Scaling law and simultaneous optical implementation of various order fractional
      Fourier transforms.

PMID- 19865237
TI  - Two-dimensional pump-probe imaging in reacting flows.

PMID- 19865236
TI  - Optimal incoherent correlator for noisy gray-tone image recognition.

PMID- 19865238
TI  - Infrared luminescence of neodymium-doped silver bromide crystals.

PMID- 19865239
TI  - Frequency stabilization to a molecular line of a diode-pumped Er-Yb laser at 1533
      nm wavelength.

PMID- 19865240
TI  - Xenon excimers produced from xenon clusters in a quasi-continuous-wave jet
      discharge.

PMID- 19865241
TI  - Effect of an irregular pattern on wavelength selectivity in a volume hologram.

PMID- 19865243
TI  - Multiplexed optical fiber interferometer based on Fourier fringe analysis.

PMID- 19865242
TI  - Real-time holographic imaging with a bacteriorhodopsin film.

PMID- 19865244
TI  - One-way image transmission with a pair of multimode optical fibers and a phase
      conjugate mirror.

PMID- 19865245
TI  - Solutions to the synthesis problem of optical delay line filters.

PMID- 19865247
TI  - Detection of subwavelength Goos-Hanchen shifts from near-field intensities: a
      numerical simulation.

PMID- 19865246
TI  - Analog optical phase modulator based on chiral smectic and polymer cholesteric
      liquid crystals.

PMID- 19865248
TI  - Autocorrelation hole in nonlinear image detectors: an estimate using an auxiliary
      photomultiplier.

PMID- 19865249
TI  - Schwarzschild soft-x-ray microscope for imaging of nonradiating objects.

PMID- 19865250
TI  - Bounds for the degree of polarization.

PMID- 19865251
TI  - Fabrication, modeling, and characterization of form-birefringent nanostructures.

PMID- 19865253
TI  - Guided lock acquisition in a suspended Fabry-Perot cavity.

PMID- 19865252
TI  - Use of a Shack-Hartmann wave-front sensor to measure deviations from a Kolmogorov
      phase spectrum.

PMID- 19865254
TI  - Kerr slice-based nonlinear interferometer with two-dimensional feedback: control
      of roll and hexagon formation.

PMID- 19865255
TI  - Light-induced second-harmonic generation in an octupolar dye.

PMID- 19865256
TI  - Phase-matched guided-wave optical bistability in chi ((2)) optical resonators.

PMID- 19865257
TI  - Observation of spontaneously frequency-shifted beam fanning in photorefractive
      Bi12SiO20.

PMID- 19865258
TI  - Real and imaginary components of the third-order nonlinearity of polyaniline
      dodecylbenzenesulfonic salt.

PMID- 19865259
TI  - Stable self-trapping and ring formation in polydiacetylene para -toluene
      sulfonate.

PMID- 19865260
TI  - Photoinduced absorption in thulium-doped ZBLAN fibers.

PMID- 19865261
TI  - Clustering-induced nonsaturable absorption phenomenon in heavily erbium-doped
      silica fibers.

PMID- 19865262
TI  - Recovery of solitons with nonlinear amplifying loop mirrors.

PMID- 19865263
TI  - Anisotropic diffusion of the state of polarization in optical fibers with
      randomly varying birefringence.

PMID- 19865264
TI  - High-power 467-nm passively locked signal-resonant sum-frequency laser.

PMID- 19865265
TI  - Quasi-three-level room-temperature Nd:YAG ring laser with high single-frequency
      output power at 946 nm.

PMID- 19865267
TI  - Ultrabroadband flat continuum generation in multichannel propagation of terrawatt
      Ti:sapphire laser pulses.

PMID- 19865266
TI  - Two-wavelength laser-diode heterodyne interferometry with one phasemeter.

PMID- 19865268
TI  - Optical header recognition by spectroholographic filtering.

PMID- 19865269
TI  - Differentiating optical correlator.

PMID- 19865270
TI  - Continuous coherent transient optical processing in a solid.

PMID- 19865271
TI  - Two-port photorefractive joint-transform correlator.

PMID- 19865272
TI  - Complex photonic band structures of a conductive metal lattice by a quadratic
      eigensystem.

PMID- 19865273
TI  - Quadrature squeezed light generation by cross-phase modulation in semiconductors.

PMID- 19865274
TI  - Generation of amplitude-squeezed light from a room-temperature Fabry-Perot
      semiconductor laser.

PMID- 19865275
TI  - Enhanced loading of a two-color vapor-cell magneto-optical trap for sodium atoms.

PMID- 19865276
TI  - Single-molecule detection by two-photon-excited fluorescence.

PMID- 19865277
TI  - Light force cooling, focusing, and nanometer-scale deposition of aluminum atoms.

PMID- 19865278
TI  - Recording lightspace so shadows and highlights vary with varying viewing
      illumination.

PMID- 19865279
TI  - Experimental demonstration of temporal-waveform-controlled spatial routing of
      optical beams by spatial-spectral filtering.

PMID- 19865280
TI  - Wavelength-division and spatial multiplexing using tandem interferometers for
      Bragg grating sensor networks.

PMID- 19865281
TI  - 50-Gbit / s optical pulse storage ring using novel rational-harmonic modulation.

PMID- 19865282
TI  - Polarization mode dispersion minimization in fiber-wound piezoelectric cylinders.

PMID- 19865283
TI  - Tumor detection in mice by measurement of fluorescence decay time matrices.

PMID- 19865284
TI  - Scattering by plasmon polaritons on a metal surface with a detuned roughness
      spectrum.
AB  - The effects of plasmon polariton excitation on a metal surface with weak one
      dimensional roughness are studied experimentally. It is shown that backscattering
      enhancement requires the excitation of counterpropagating polaritons, whereas
      surface waves traveling in one direction produce diffuse scatter without a strong
      backscattering peak.

PMID- 19865285
TI  - Boundaryless beam propagation.
AB  - A new beam-propagation scheme based on a finite-difference algorithm is proposed.
      The main property of this scheme is to avoid the boundary conditions altogether,
      by mapping the infinite space onto a finite-size domain. This mapping, together
      with a rescaling of the field, leads to a fast and easy-to-implement algorithm
      that can be used when boundary condition constraints are important.

PMID- 19865286
TI  - All-optical three-dimensional mapping of 180 degrees domains hidden in a BaTiO(3)
      crystal.
AB  - We present three-dimensional, high-contrast maps of 180 degrees domains hidden
      inside photorefractive crystals of BaTiO(3). Some domains are columns that run
      the entire length of the crystal, whereas others are short needles that begin
      predominantly on the -c surface but disappear inside the crystal bulk.

PMID- 19865287
TI  - Vector-beam solutions of Maxwell's wave equation.
AB  - The Hermite-Gauss and Laguerre-Gauss modes are well-known beam solutions of the
      scalar Helmholtz equation in the paraxial limit. As such, they describe linearly
      polarized fields or single Cartesian components of vector fields. The vector wave
      equation admits, in the paraxial limit, of a family of localized Bessel-Gauss
      beam solutions that can describe the entire transverse electric field. Two
      recently reported solutions are members of this family of vector Bessel-Gauss
      beam modes.

PMID- 19865288
TI  - Nanowriting on ferroelectric surfaces with a scanning near-field optical
      microscope.
AB  - We use a scanning near-field optical microscope in illumination mode with a metal
      coated optical-fiber tip to write, at ambient conditions, nanolines on triglycine
      sulfate ferroelectric surfaces. Our experiments show that, in spite of the
      cutoff, the outcoming light intensity is sufficient to modify locally the
      triglycine sulfate surface. We present images that show that, with this method,
      linewidths as small as 60 nm can be achieved that are stable over several days.

PMID- 19865289
TI  - High-order harmonic generation by subpicosecond KrF excimer laser pulses.
AB  - We investigated the generation of high-order harmonics of a KrF excimer laser (80
      mJ, 0.5 ps) in rare gases (He, Ne) and molecular gases (N(2), O(2)). The highest
      order harmonic, 7.1 nm, the 35th, was observed in He and Ne, and 8.6 nm, the
      29th, in N(2) and O(2). Our experimental results suggest that the high-order
      harmonics are emitted from ionized atoms. The maximum photon energy of the high
      order harmonics may be restricted by phase mismatching caused by free electrons.

PMID- 19865290
TI  - Ultralong dark decay measurements in BaTiO(3).
AB  - We have observed dark decay rates in BaTiO(3) crystals at elevated temperatures
      that correspond to dark decay times as long as 2200 years at room temperature.
      Our investigations have shown that cerium is a desirable dopant in BaTiO(3) for
      enhancing the dark storage time.

PMID- 19865291
TI  - Degenerate four-wave mixing geometry in thin-film waveguides for nonlinear
      material characterization.
AB  - We demonstrate experimentally a new degenerate four-wave mixing (DFWM) geometry
      in waveguides that permits the simultaneous determination of the nonlinear
      refractive index, the absorption, and the response time of the thin-film
      materials. The geometry consists of two guided pumps in a planar waveguide with
      an unguided probe. We achieve nonlinear characterization by measuring only the
      DFWM signal and the guided pump power at the waveguide output. The technique has
      been tested on a polymeric film (di-alkylaminonitro- stilbene).

PMID- 19865292
TI  - Self-focusing and self-trapping of optical beams upon photopolymerization.
AB  - We demonstrate theoretically and experimentally that optical beams are self
      focused and self-trapped upon initiating photopolymerization. This unique
      nonlinear optical phenomenon is dependent on the optical exposure and produces
      permanent index-of-refraction changes larger than 0.04. The resulting nonlinear
      wave equation is shown to be nonlocal in time and displays self-trapped solutions
      only for sufficiently low average optical intensities.

PMID- 19865293
TI  - All-fiber tunable filter and laser based on two-mode fiber.
AB  - We demonstrate an all-fiber acousto-optic tunable filter based on two-spatial
      mode coupling, with improved ruggedness and efficiency, by using a new acoustic
      transducer design. We use a rigorous modeling of the flexural acoustic wave to
      analyze the mode coupling with better accuracy. Using the acousto-optic tunable
      filter, we demonstrate a novel all-fiber tunable laser with a tuning range of
      more than 20 nm and a linewidth of 0.2 nm.

PMID- 19865294
TI  - Digital pulse-position modulation of optical fiber solitons.
AB  - Amplitude-shift keying modulation of solitons is subject to limited capacity
      because of Gordon-Haus noise and soliton interaction. It is shown theoretically
      that the capacity can be increased beyond this limit by recoding of the
      modulation. The design strategy is to make the pulse train strongly interacting,
      which reduces the Gordon-Haus noise, and to apply subband coding to counter the
      effects of the information dispersion caused by the strong intersoliton
      interaction; the subband-coded complex is pulse-position modulated onto the
      soliton stream. An example shows a 2.35-times improvement in capacity at the
      transatlantic distance of 6000 km with this method.

PMID- 19865295
TI  - Dispersion bistability of a reflective fiber-optic mode converter.
AB  - A novel nonlinear device based on a reflective fiber-optic LP(01) ? LP(02) mode
      converter is proposed. The dispersion effect of optical bistability, i.e., the
      bistability with respect to the input wavelength, is investigated. Our results
      show that, when the input wavelength shifts to a wavelength shorter than the
      Bragg wavelength of the fiber's distributed-feedback structure, the threshold of
      the switching power for the optical bistability can be reduced. In addition, it
      is shown that both the switch-on and the switch-off threshold powers for a
      nonlinearity reflective LP(01) ? LP(02) mode converter are much lower than those
      of a conventional nonlinear fiber Bragg grating reflector.

PMID- 19865296
TI  - Direct three-dimensional image transmission through single-mode fibers with
      monochromatic light.
AB  - Direct three-dimensional image transmission through one single-mode or multimode
      fiber is demonstrated. Image transmission is carried out with a grating
      interferometer under monochromatic, spatially incoherent illumination.

PMID- 19865297
TI  - Reduction of collision-induced time jitters in dispersion-managed soliton
      transmission systems.
AB  - Nonadiabatic effects caused by lumped amplifiers in fiber soliton transmission
      systems are reduced by the use of dispersion-decreasing fibers between
      amplifiers. As a practical application, we consider a stepwise dispersion
      decreasing fiber with M steps and show that the increase in M is almost
      equivalent to the reduction of amplifier spacing, Z(a), to Z(a)/M in reducing
      collision-induced jitters in soliton-based wavelength-division multiplexing
      systems.

PMID- 19865298
TI  - Efficient coupling into tapered proton-exchanged LiNbO(3) waveguides fabricated
      by vertically controlled immersion.
AB  - Planar LiNbO(3) waveguides with a 5-mm tapered region and a 10-mm homogeneous
      slab waveguide region were fabricated by a double proton-exchange process. The 4
      microm waveguide entrance gives rise to a coupling efficiency as high as 93%; the
      precise control of the depth profile of the tapered region results in a low 1-dB
      power transfer loss from the tapered region to the 0.4-microm-depth working
      region. The techniques developed provide an alternative to prism coupling into
      planar waveguides in Cerenkov second-harmonic generation applications.

PMID- 19865299
TI  - Diode-pumped, continuous-wave, single-mode, tunable Cr(3+):LiSrAlF(6) ring laser.
AB  - We describe an all-solid-state, tunable, single-frequency, continuous-wave
      Cr(3+):LiSrAlF(6) ring laser. When pumped with 360 mW of power from a single
      laser diode the laser has tuning range from 814 to 892 nm and a free-running
      frequency stability relative to a reference cavity of 60 kHz rms. Further
      stabilization promises to be possible by use of standard servo electronics. We
      demonstrate the use of the laser by performing Dopplerfree saturation
      spectroscopy of the cesium D2 line.

PMID- 19865300
TI  - Investigation of diode-pumped 2.8-microm laser performance in Er:BaY(2)F(8).
AB  - Laser operation at 2.8 microm in BaY(2)F(8) with erbium concentrations of 7.5%
      and 20% is investigated under laser-diode pumping at 967 nm. Output powers as
      high as 250 mW and slope efficiencies as high as 24% are obtained. Results are
      comparable with those of Er(3+):LiYF(4) under the same pump conditions. Slope
      efficiencies above 30% are predicted for optimized erbium concentrations.

PMID- 19865301
TI  - Compact diode-pumped all-solid-state femtosecond Cr(4+):YAG laser.
AB  - We have developed a compact, all-solid-state self-mode-locked Cr(4+):YAG laser.
      The laser is pumped by a cw laser-diode-pumped Nd:YVO(4) laser and produces
      highly stable femtosecond pulses near 1.50 microm. Measurements of noise power
      spectra for frequencies below 10 kHz show that the diode-pumped laser system
      greatly improves the output energy fluctuation and pulse timing jitter compared
      with a laser system that uses a conventional arc-lamp-pumped cw Nd:YAG laser.

PMID- 19865302
TI  - Pulsed diode-pumped additive-pulse mode-locked high-peak-power Nd:YLF laser.
AB  - Intense ultrashort pulses are generated in an additive-pulse mode-locked,
      amplitude-feedback-controlled Nd:YLF laser pumped by quasi-cw laser diodes with a
      30-Hz repetition rate. Pulse trains are produced that consist of approximately
      600 single pulses of 2.1-ps duration and less, similar1-microJ energy. The peak
      intensity is less, similar0.5 MW, and a stability corresponding to a standard
      deviation of ~1.3% is measured. The optical efficiency of this all-solid-state
      mode-locked laser is determined to be ~1%.

PMID- 19865303
TI  - Cavity dumping of fiber lasers by phase-modulated optical loop mirrors.
AB  - We report the generation of high-repetition-rate pulses from an erbium-doped
      fiber laser with a phase-driven optical loop mirror as a cavity dumper. The
      result demonstrates the potential of this novel method for efficient and
      ultrafast cavity dumping of fiber lasers.

PMID- 19865304
TI  - Counting, timing, and tracking with a single-photon germanium detector.
AB  - We report the performance of a germanium quad-cell, composed of four avalanche
      photodiodes operated in the photon-counting regime, biased above the breakdown
      voltage. Each pixel detects a single photon in the wavelength range 1-1.5 microm
      with ~10% quantum efficiency and measures the photon arrival time with a time
      resolution of 100 ps. By adopting a multiplexed gating of the avalanche
      photodiodes we avoided the optical cross talk among pixels, thus achieving a
      noise-equivalent power of 3 x 10(-15) W/Hz((1/2)) for each pixel and
      demonstrating the tracking capabilities of such a detector.

PMID- 19865305
TI  - Conical emission from self-guided femtosecond pulses in air.
AB  - Conical emission in the forward direction is observed from intense femtosecond
      light pulses propagating through air over long distances. The conical emission is
      attributed to Cerenkov radiation from a dynamic self-guiding structure consisting
      of a weakly ionized core surrounded by Kerr cladding.

PMID- 19865306
TI  - Space-time coupling and collapse threshold for femtosecond pulses in dispersive
      nonlinear media.
AB  - Femtosecond space-time coupling effects in dispersive nonlinear media are
      investigated by a simple approximate method. The applicability of the method is
      verified by comparison with earlier numerical simulations. New results are
      presented for astigmatic beams as well as for negative dispersion. The position
      of the beam waist in the material changes the collapse threshold. For astigmatic
      beams, collapse is prevented for pulse durations shorter than a critical value.

PMID- 19865307
TI  - Pulse compression by nonlinear pulse evolution with reduced optical wave breaking
      in erbium-doped fiber amplifiers.
AB  - Nonlinear pulse evolution is studied for a fiber with normal dispersion (ND) and
      gain. Numerical simulations show that under certain conditions the pulse evolves
      into a parabolic shape, which has been shown to reduce optical wave breaking.
      Much as with the square pulse that forms in passive fibers with ND, the interplay
      of ND and self-phase modulation creates a highly linear chirp, which can be
      efficiently compressed. Application to an amplifying fiber/grating (prism) pair
      pulse compressor is considered, with an experimental demonstration of compression
      from 350 to 77 fs at a gain of 18 dB in an erbium-doped fiber amplifier.

PMID- 19865308
TI  - Optical coherent transient header/data isolation technique.
AB  - We experimentally demonstrate a novel, all-optical technique that spatially
      isolates two parts of a temporally encoded optical information stream from each
      other by means of spatial-spectral holographic technology. A brief reference
      pulse is applied to an inhomogeneously broadened absorber [Tm(3+):YAG (0.1 at. %)
      at ~4.4 K] in the direction opposite that of the information stream, overlapping
      it on a boundary between the two temporal parts to be isolated (i.e., the header
      and the data). Another brief reference pulse subsequently applied in the opposite
      (the same) direction as that of the information stream results in an emitted
      optical output that mimicks only the part of the information stream that follows
      (precedes) the first reference pulse in a timeforward (time-reversed) fashion,
      completely isolated from the other part.

PMID- 19865309
TI  - Measurement of the lifetime of the atomic cesium 5(2)D(5/2) state with diode
      laser excitation.
AB  - The lifetime of the atomic cesium 5(2)D(5/2) state was measured with time
      correlated single-photon counting spectroscopy. Ground-state cesium atoms were
      excited with a diode laser by use of an electric quadrupole transition. Analysis
      of the exponential decay of the cascade photons from the 6(2)P(3/2) state yields
      a 5(2)D(5/2) lifetime of 1225(12) ns.

PMID- 19865310
TI  - CO(2) laser trap for cesium atoms.
AB  - We demonstrate a quasi-electrostatic trap for cold Cs atoms, using a focused 20-W
      CO(2) laser beam (lambda = 10.6 microm). Excluding background gas collisions, we
      measure a trap loss rate of 0.30(33) atoms/s, which is consistent with the
      calculated photon-limited loss rate of 3 x 10(-11) atoms/s. We measure a ground
      state hyperfine population relaxation lifetime of at least 10 s.

PMID- 19865311
TI  - Wavelength-selective planar holograms.
AB  - Planar gratings and holograms are normally readout-wavelength insensitive. We
      show, however, that a binary phase surface-relief hologram can be transparent at
      one wavelength (lambda) yet diffract efficiently at another (lambda'), provided
      that the phase delay is an integer number of waves (e.g., 3) at lambda and a half
      integer number of waves (e.g., 2.5) at lambda'. We fabricated a 7.9-microm-deep
      binary phase grating in BK7 glass that separates the standard telecommunications
      wavelengths, 1.3 and 1.55 microm, with 80% efficiency (neglecting Fresnel losses)
      and greater than 30:1 contrast.

PMID- 19865312
TI  - Fast random access to frequency-selective optical memories.
AB  - Spectral phase codes are used as storage addresses in a frequency-selective
      optical memory. Data are engraved over a 1.5-THz-wide spectral interval. With the
      help of a ferroelectric liquid-crystal modulator it takes less than 100 micros to
      retrieve any spectrally addressed data.

PMID- 19865313
TI  - Detection of CO in air by diode-pumped 4.6-microm difference-frequency generation
      in quasi-phase-matched LiNbO(3).
AB  - Detection of CO, N(2)O, and CO(2) in ambient air was performed with a room
      temperature cw IR source based on difference-frequency generation in periodically
      poled LiNbO(3). The source was pumped by a seeded highpower GaAlAs amplif ier at
      860 nm and a diode-pumped monolithic Nd:YAG ring laser at 1064 nm. The IR output
      was tunable between 2160 and 2320 cm(-1) without crystal rotation. The CO
      detection sensitivity is extrapolated to 5 ppb m/ radicalHz if limited by IR
      intensity noise.

PMID- 19865314
TI  - Sixteen-beam grating-based division-of-amplitude photopolarimeter.
AB  - A 16-beam grating-based division-of-amplitude photopolarimeter that employs a
      transmission grating and a linear photodiode detector array has been developed
      and tested. The transmission grating splits the incident light beam into 16
      orders with essentially uniform intensity distribution. Linear polarizers are
      placed in fanned-out azimuth orientations in different orders, and a quarter-wave
      retarder is inserted in one order. After calibration, the photopolarimeter makes
      time-resolved measurements of all the Stokes parameters of the incident light
      with a precision of 0.001. The calibration and testing of the system at 632.8 nm
      are presented.

PMID- 19865315
TI  - Mode-locked fiber laser gyroscope based on a distributed-feedback semiconductor
      laser amplifier.
AB  - A mode-locked fiber laser gyroscope is reported that uses a distributed-feedback
      semiconductor laser amplif ier as the gain medium. Stable mode-locked optical
      pulses were obtained without gain competition, and the pulse interval could be
      measured with much-improved accuracy as a function of rotation rate. The rms
      noise equivalent rotation rate was measured to be 0.4 deg/ radicalh.

PMID- 19865316
TI  - Angular dependence of light transmittance through a polymer-dispersed liquid
      crystal above threshold.
AB  - The transmittance of polymer-dispersed liquid crystals (PDLC's) can be easily
      controlled by a low-frequency electric field. However, unlike glass, even in its
      transparent state a PDLC is an anisotropic material, so its transmittance has a
      characteristic angular dependence. We introduce a mathematical model to describe
      the angular dependence of the light transmittance through a PDLC sample above
      threshold. The accuracy of the model is tested and predictions compared with
      experimental measurements.

PMID- 19865318
TI  - Picosecond nonlinear refraction measurement in single-beam open Z scan by charge
      coupled device image processing.
AB  - We propose a picosecond single-beam open Z-scan experiment in which the usual
      apertured detection scheme is replaced by a two-dimensional single-shot CCD
      camera. This enables us to extract the two-dimensional transverse modifications
      of the whole far-f ield pattern that are due to nonlinear refraction as well as
      to measure the induced nonlinear phase shift with increased sensitivity compared
      with that of the conventional Z scan.

PMID- 19865317
TI  - Full vectorial analysis of a nonlinear slab waveguide based on the nonlinear
      hybrid vector finite-element method.
AB  - We propose a new nonlinear hybrid vector f inite-element method to study the
      propagation of an optical beam in a nonlinear waveguide in three space
      dimensions. The new method is a combination of the edge-element and f inite
      difference methods; the former applies to the waveguide cross section and the
      latter to the propagation direction. To validate our method, a planar nonlinear
      waveguide (consisting of a linear substrate, a linear film, and a Kerr-type
      cladding) that is end-fire excited by the TE(0) and TM(0) modes is studied
      numerically. We demonstrate that the external excitation of a nonlinear slab
      waveguide can produce sequential threshold behavior by means of multisoliton
      emission from the waveguide.

PMID- 19865319
TI  - Sagnac interferometric intensity-dependent refractive-index measurements of
      polymer optical fiber.
AB  - We have applied a new modified Sagnac interferometric technique to measure the
      real part of the intensitydependent refractive index of a single-mode polymer
      optical fiber. For a 0.1% by weight squaraine dye in a poly(methyl methacrylate)
      core, Re([chi((3))1111]) is 12(+/-7) x 10(-13) cm(3)/erg at lambda = 1064 nm. We
      discuss the effect of these measurements on all-optical devices.

PMID- 19865320
TI  - Generation of 340-nm light by frequency doubling of a laser diode in bulk
      periodically poled LiTaO(3).
AB  - Frequency doubling of a 680-nm laser diode in periodically poled LiTaO(3) is
      presented. By selective proton exchange followed by high-voltage pulse
      application, a second-order periodic domain inversion having uniform periodicity
      and optimum duty cycle was fabricated over a 10-mm interaction length in a 200
      microm-thick LiTaO(3) substrate. A 340-nm wavelength of harmonic ultraviolet
      light was generated in a single pass through the domain-inverted structure.

PMID- 19865321
TI  - Wavelength-shift-free spectral inversion with an optical parametric loop mirror.
AB  - A spectral-inversion technique with no wavelength shift is presented that
      utilizes a novel four-wave mixing (FWM) scheme named the optical parametric loop
      mirror. This scheme eliminates both the input signal wave and the nondegenerate
      pump waves from the FWM wave generated at the signal wavelength. The compensation
      of waveform distortion caused by fiber chromatic dispersion is successfully
      demonstrated by the proposed method.

PMID- 19865322
TI  - Influence of optical source characteristics on the measurement of polarization
      mode dispersion of highly mode-coupled fibers.
AB  - A new theoretical analysis of the interferometric polarization-mode dispersion
      (PMD) measurement predicts, in the limit of large PMD, a new relationship to the
      highly mode-coupled principal states model. This theory is confirmed by computer
      simulation of the ratio of the mean differential group delay (DGD) to the
      interferometric PMD. Jones matrix eigenanalysis and wavelength scanning with
      extrema counting are shown to measure the mean DGD independently of the optical
      source spectrum, whereas interferometrically measured PMD is shown to depend on
      the optical source spectrum as well as on the characteristics of the fiber to be
      measured.

PMID- 19865323
TI  - Ultrahigh-bit-rate soliton communication systems using dispersion-decreasing
      fibers and parametric amplifiers.
AB  - We study analytically and numerically soliton communication links made by use of
      dispersion-decreasing fibers and parametric amplif iers. We show that bit rates
      greater than 100 Gbits/s (one channel, one polarization) can be achieved with
      large amplif ier spacings (as high as 120 km). The Raman effect and soliton
      interactions are compensated through optical phase conjugation, whereas fiber
      losses and third-order dispersion are handled through tailoring of the dispersion
      profile of a dispersion-decreasing fiber.

PMID- 19865324
TI  - Acoustic effect and correlated errors in soliton information transmission.
AB  - The acoustic effect signif icantly increases the timing jitter of solitons in
      communication lines. We calculate the correlation in near-neighbor soliton time
      shifts that result from the acoustic interaction and show that the acoustic
      effect can cause correlated errors that cannot be corrected with standard, simple
      error-correction codes such as the Hamming code.

PMID- 19865325
TI  - Array of photorefractive waveguides for massively parallel optical
      interconnections in lithium niobate.
AB  - An array of photorefractive (PR) waveguides is proposed for massively parallel
      optical interconnections. The array of PR waveguides can be fabricated in a
      lithium niobate crystal by illumination of an interference fringe pattern formed
      by plane waves. We numerically calculate the maximum density of the PR waveguides
      when the coupling between the PR waveguides is negligible. Experiments for the
      fabrication and guiding tests of the array of two-dimensional PR waveguides are
      demonstrated.

PMID- 19865326
TI  - 1-kW, room-temperature, fast-axial-flow CO laser excited by a radio-frequency
      discharge.
AB  - A fast-axial-flow rf-discharge-excited CO laser has been scaled up to produce an
      output power of more than 1 kW at room temperature (280-290 K). The discharge
      section is composed of eight discharge tubes, to which rf power is capacitively
      coupled. An output power of 1220 W is obtained with an Xe-added mixture, with
      corresponding electrical conversion eff iciency and specific output of 7.9% and
      1.8 W/cm(3), respectively. Scaling characteristics of the scheme are discussed.
      The temperature dependence of the output, the output stability, and the beam
      properties are also reported.

PMID- 19865327
TI  - Alexandrite-pumped alexandrite regenerative amplifier for femtosecond pulse
      amplification.
AB  - We demonstrate a regenerative amplif ier incorporating alexandrite as the gain
      medium that is pumped by an alexandrite laser. Temperature-altered gain permitted
      the 728-nm alexandrite pump laser, operating at room temperature, to pump a 780
      800-nm alexandrite laser that was maintained at elevated temperatures. 200-fs
      pulses from a Ti:sapphire oscillator were amplif ied to the millijoule level.
      This system also amplif ied femtosecond pulses from a frequency-doubled Er-doped
      fiber laser.

PMID- 19865328
TI  - High-power, high-repetition-rate picosecond optical parametric oscillator for the
      near- to mid-infrared.
AB  - A high-repetition-rate, singly resonant optical parametric oscillator based on
      KTiOAsO(4) and synchronously pumped by a self-mode-locked Ti:sapphire laser is
      reported. Under the conditions of pump-tuned noncritical type II phase matching,
      average near-infrared output powers of 403 mW have been generated at a repetition
      rate of 81 MHz. With the available mirror set, signal tuning over 1.116-1.281
      microm and idler tuning over 2.260-3.160 microm are demonstrated for a range of
      pump wavelengths. Without dispersion compensation, signal (idler) pulses with
      durations of 1.01-1.03 (1.61-2.91) ps have been obtained for 1.2-ps input pump
      pulses.

PMID- 19865329
TI  - Compact Kerr-lens mode-locked resonators.
AB  - We present a comparison of compact three-element Ti:Al(2)O(3) laser resonator
      designs for enhanced Kerr-lens mode locking. We demonstrate a novel compact
      cavity design that uses an intracavity lens and show that nonastigmatic modes can
      signif icantly increase Kerr-lens action and achieve self-starting mode locking.
      A new mechanism for group-velocity dispersion that arises from the chromatic
      aberration of the intracavity focusing elements is also demonstrated.

PMID- 19865330
TI  - Femtosecond fiber laser pulses amplified by a KCl:Tl+ color-center amplifier for
      continuum generation in the 1.5-microm region.
AB  - A diode-pumped stretched-pulse additive-pulse mode-locked Er-doped fiber laser is
      used to seed a KCl:Tl + color-center amplif ier crystal. The initial l-nJ chirped
      pulses are double passed through the amplif ier, which is pumped by a 1-kHz Q
      switched Nd:YAG laser. The resulting 10-microJ pulses are then chirp compensated
      to 250-fs duration and are used to generate a spectral continuum. A few high-n(2)
      materials are investigated for continuum generation, and spectral slicing of the
      continuum is demonstrated.

PMID- 19865331
TI  - Production of 30-fs pulses tunable throughout the visible spectral region by a
      new technique in optical parametric amplification.
AB  - A multipass optical parametric amplif ier is pumped by a 250-kHz microjoule-level
      Ti:sapphire regenerative amplif ier system. Tuning each pass of the amplif ier to
      provide gain for slightly different spectral regions of a white-light continuum
      source produces broadband pulses that may be compressed to less than 30 fs.

PMID- 19865332
TI  - Direct ultrashort-pulse intensity and phase retrieval by frequency-resolved
      optical gating and a computational neural network.
AB  - Ultrashort-laser-pulse retrieval in frequency-resolved optical gating has
      previously required an iterative algorithm. Here, however, we show that a
      computational neural network can directly and rapidly recover the intensity and
      phase of a pulse.

PMID- 19865333
TI  - chi((3)) squeezed vacuum generation without a Sagnac interferometer.
AB  - We show that an intense linearly polarized pulse propagating in a nonbirefringent
      fiber squeezes the perpendicularly polarized vacuum f luctuations through cross
      phase modulation. Unlike the generation of squeezed vacuum through self-phase
      modulation, the mechanism discussed here does not require the use of a nonlinear
      Sagnac interferometer to separate the pump from the squeezed vacuum.

PMID- 19865334
TI  - Polarization temporal dynamics in a dye microlaser.
AB  - We have investigated the temporal dynamics of the output polarization of a dye
      microlaser operating in a transient regime, i.e., under femtosecond excitation.
      In these conditions the dipole angular diffusion has an important role in the
      formation of the microlaser pulse, as is shown in a theoretical model. By
      performing the experiment for different values of the microcavity length and
      varying the polarization angle, we measured threshold and buildup time of the
      microlaser and compared the results obtained with two dye solutions of different
      viscosity. The agreement between theory and experimental results is adequate.

PMID- 19865335
TI  - Avoiding hologram bending in photorefractive crystals.
AB  - Dynamic coupled-wave theory predicts the bending of recorded hologram phase
      planes in most photorefractive crystals. Bent holograms occur in LiNbO(3) and
      other photovoltaic crystals that are particularly interesting as holographic
      storage media and result in a reduced overall diffraction eff iciency. We show
      that hologram bending in LiNbO(3) can be avoided or at least sensibly reduced by
      use of an actively stabilized recording technique.

PMID- 19865336
TI  - Realization of novel monolithic free-space optical disk pickup heads by surface
      micromachining.
AB  - A novel monolithic free-space optical disk pickup head has been fabricated by
      micromachined micro-optical bench technology. The pickup head contains a self
      aligned semiconductor edge-emitting laser, a collimating lens, a beam splitter,
      two focusing lenses, and two 45 degrees mirrors. All optical components are built
      monolithically on Si substrates. The 45 degrees mirror directs the optical output
      beam in the surface-normal direction. This novel design could signif icantly
      reduce the size and the weight of the optical pickup head as well as the cost of
      the assembly processes. The weight reduction could also greatly increase the data
      access rate.

PMID- 19865337
TI  - Fluorescence lifetime imaging in turbid media.
AB  - The lifetime of a f luorophore generally varies in different environments, making
      the molecule a sensitive indicator of tissue oxygenation, pH, and glucose.
      However, lifetime measurements are complicated when the f luorophore is embedded
      in an optically thick, highly scattering medium such as human tissue. We
      formulate the inverse problem for f luorescence lifetime tomography using diffuse
      photon density waves, and we demonstrate the technique by deriving spatial images
      of heterogeneous f luorophore distribution and lifetime, using simulated
      measurements in heterogeneous turbid media.

PMID- 19865338
TI  - Temporal gating in highly scattering media by the degree of optical polarization.
AB  - The temporal profiles of polarized laser pulses propagating through a scattering
      medium differ for scattered light parallel and perpendicular to the incident
      polarization. The degree of polarization is conserved over 100 ps after the
      arrival of the ballistic component. This observation can be used as a time gate
      for the early portion of the scattered light, reducing the diffusive component.

PMID- 19865339
TI  - Time-bandwidth product of chirped sech(2) pulses: application to phase-amplitude
      coupling factor measurement: addendum.

PMID- 19865340
TI  - Scanning plasmon optical microscope operation in atomic force microscope mode.
AB  - A scanning plasmon optical microscope has been operated with an atomic force
      microscope rather than a scanning tunnel microscope to scan a surface. The
      instrument produced a nanoscale optical image of dyemolecule crystals adsorbed on
      a silver film. Images of dye-molecule crystal islands are presented.

PMID- 19865341
TI  - Transformation of a laser beam intensity profile by a deformable mirror.
AB  - We developed a deformable mirror with nine actuators for transformation of a
      laser beam intensity profile. A circular-cross-section Gaussian beam was
      successfully transformed into a rectangular-cross-section beam by the deformable
      mirror with conservation of spatial coherency.

PMID- 19865342
TI  - Observation of thermal noise in a dynamically biased fiber-optic gyro.
AB  - The effect of phase noise caused by thermal f luctuations in optical fiber is
      observed experimentally in a dynamically biased open-loop fiber-optic gyro. When
      source noise subtraction is used, thermal noise effects are readily observable.
      Total noise levels are in good agreement with theory. Contributions from shot,
      thermal, and electronic noise to the random walk coefficient are calculated, and
      the total is compared with experiment.

PMID- 19865343
TI  - Maskless photoencoded selective etching for glass-based microtechnology
      applications.
AB  - Two-photon excitation of carriers in boron E'-center-containing borosilicate
      glasses results in a photoencoding of selectively etchable regions. Using a
      turbulent etching process followed by polishing, we have demonstrated a number of
      patterning capabilities for microtechnology applications such as ultrafast
      capillary electrophoresis chips and rapid prototyping of diffractive optical
      elements.

PMID- 19865344
TI  - Diffractive lens fabricated with mostly zeroth-order gratings.
AB  - We demonstrate a spherical diffractive lens fabricated in fused quartz for use at
      the 632.8-nm wavelength. The lens is constructed by use of a modulated two
      dimensional binary grating with a high transmitted zerothorder efficiency.
      Rigorous eigenmode analysis is used to correlate the desired phase modulation
      with the fill factor. Fabrication requires only one lithography step. Using the
      lens, we were able to image a focal spot with a diffraction-limited spot size
      (FWHM).

PMID- 19865345
TI  - Femtosecond time-resolved Z-scan investigations of optical nonlinearities in
      ZnSe.
AB  - Degenerate (single-color) and nondegenerate (two-color) time-resolved Z-scan
      techniques, with femtosecond time resolution,have been implemented to measure the
      magnitude and dynamical processes of the optical nonlinearities of ZnSe. In the
      time-resolved Z-scan spectra a reversal of sign in the refractive-index change
      Deltan as a function of time delay was observed. A bound electronic contribution
      with a resolution limited response s,200 fs) gave rise to a positive Deltan at
      zero time delay, whereas a free-carrier contribution resulted in a negative
      Deltan at longer time delays. The free-carrier contribution to Deltan has two
      initial rapid relaxation components with time constants of a few picoseconds and
      a few tens of picoseconds, respectively. The longlived carriers also contributed
      to a slow relaxation component in Deltan on a nanosecond time scale.

PMID- 19865346
TI  - Exact solution to photorefractive and photochromic two-wave mixing with arbitrary
      dependence on fringe modulation.
AB  - An exact solution to the slowly varying envelope wave equations for two-wave
      mixing with both photorefractive and photochromic gratings present and with an
      arbitrary dependence of the gain and absorption on the fringe modulation is
      obtained.

PMID- 19865347
TI  - Direct measurement of photoinduced charge distribution responsible for second
      harmonic generation in glasses.
AB  - We have found that borosilicate glasses that produce second-harmonic generation
      after simultaneous irradiation by fields at omega and 2omega exhibit postexposure
      selective etching. We use the charge specificity of the selective etching process
      to spatially map the photoexcited electron distributions responsible for second
      harmonic generation. The results show that nearly symmetric nondipolar charge
      distributions exist for some regimes of encoding and that, at higher intensities,
      a nearly dipolar distribution is produced.

PMID- 19865348
TI  - One-dimensional spatial soliton dragging, trapping, and all-optical switching in
      AlGaAs waveguides.
AB  - We report the dragging and mutual trapping of two initially overlapped,
      orthogonally polarized, onedimensional spatial solitons in an AlGaAs slab
      waveguide. Using this effect, we realized an all-optical switch that had an
      on/off switching contrast of ~2.5:1. The contrast of the switch increased to 4:1
      when a soliton was used to drag a nonsoliton, weak beam.

PMID- 19865349
TI  - Broadband spatial mode conversion by chirped fiber bending.
AB  - We solve the coupled-mode equations for linearly chirped codirectional mode
      couplers and use the results to develop design rules for broadband couplers. By
      comparing a chirped coupler with a uniform coupler having the same effective
      coupling length we find that high coupling efficiency can be obtained over a
      substantially wider bandwidth. We design a chirped device to have a 99% bandwidth
      of 47 nm at 1090 nm, which is 5.8 times larger than for the uniform coupler.
      Experimentally the bandwidth was improved by a factor of 5.4.

PMID- 19865350
TI  - Minimum channel spacing in filtered soliton wavelength-division-multiplexing
      transmission.
AB  - We study a soliton transmission line with sliding-frequency filters, and we
      determine the limits on soliton stability imposed by the value of the free
      spectral range of Fabry-Perot etalon filters. From these limits, we infer the
      minimum channel spacing that is possible in a soliton wavelength-division
      multiplexing system.

PMID- 19865351
TI  - Blue microchip laser fabricated from Nd:YAG and KNbO(3).
AB  - A Nd:YAG/KNbO(3) composite-material microchip laser has generated blue radiation
      at 473 nm with output powers of 1 mW when diode laser pumped and 9 mW when
      Ti:sapphire laser pumped. The fundamental radiation generated by the quasi-three
      level (4)F(3/2)-(4)I(9/2) transition in Nd:YAG at 946 nm was frequency doubled in
      KNbO(3) angle cut to be type I critically phase matched at 45 degrees C. Despite
      the normally isotropic nature of Nd:YAG, the fundamental is emitted linearly
      polarized and orthogonal to the linearly polarized blue radiation.

PMID- 19865352
TI  - Diode-pumped optical parametric oscillator.
AB  - Diode-pumped optical parametric oscillation has been demonstrated for the first
      time to our knowledge in a single Nd:MgO:LiNbO(3) nonlinear crystal. The crystal
      is pumped by a semiconductor diode laser array at 812 nm. The Nd(3+) ions absorb
      the 812-nm radiation to generate 1084-nm laser oscillation. On internal Q
      switching the 1084-nm radiation pumps the LiNbO(3) host crystal that is angle cut
      at 46.5 degrees and generates optical parametric oscillation. The oscillation
      threshold that is due to the 1084-nm laser pump with a pulse length of 80 ns in a
      1-mm-diameter beam was measured to be approximately 1 mJ and produced 0.5-mJ
      output at 3400-nm signal wavelength.

PMID- 19865353
TI  - Efficient continuous-wave TEM(00) and femtosecond Kerr-lens mode-locked
      Cr:LiSrGaF laser.
AB  - Efficient high-power (900-mW) TEM(00) cw operation of a Cr:LiSrGaF laser pumped
      by a Kr(+) laser is demonstrated. The results of laser and spectroscopic
      analysis, including upconversion and excited-state absorption, are presented and
      used for the optimization of this laser. Kr(+)-laser-pumped mode-locked
      femtosecond operation (64 fs) was performed. Use of a modified resonator, which
      can decrease the threshold pump and intracavity power for Kerr-lens mode locking
      and increase the mode-locked output power (300 mW), is suggested. The inf luence
      of crystal axis misalignment on the tuning and mode-locking characteristics of
      the laser is studied.

PMID- 19865354
TI  - Soliton fiber laser with a hybrid saturable absorber.
AB  - We present an experimental study of a picosecond fiber soliton laser in which
      mode locking is achieved by the combined action of a multiple-quantum-well
      saturable absorber and a nonlinear amplifying loop mirror. In this configuration
      the multiple-quantum-well sample acts not only as a saturable absorber but also
      as a passive phase modulator, while the inclusion of a nonlinear amplifying loop
      mirror fixes the energy of the generated pulses. The laser stably operates at a
      repetition rate of 250 MHz with a timing jitter below 10 ps.

PMID- 19865355
TI  - 62-W cw TEM(00) Nd:YAG laser side-pumped by fiber-coupled diode lasers.
AB  - We describe the laser performance and thermal properties of side-pumped Nd:YAG
      rod lasers that use ibercoupled diode lasers as pump sources. Utilizing a nearly
      homogeneous pump light profile, we realize an output power of more than 60 W in
      TEM(00) mode operation with optical-to-optical efficiencies of more than 25%. In
      multimode operation, optical slope efficiencies of more than 46% are observed.

PMID- 19865356
TI  - 30-THz upconversion of an AlGaAs diode laser with AgGaS(2): bridging the several
      terahertz frequency gap in the near infrared.
AB  - We report as much as 6-micro W upconverted cw radiation at lambda = 778 nm from
      the sum-frequency mixing of a 50-mW diode laser at lambda = 842 nm and a 200-mW
      CO(2) laser at lambda = 10.2 microm by use of a 15-mm-long silver thiogallate
      crystal. This nonlinear material provides a convenient connection between IR and
      visible/near-IR optical standards. We describe simple frequency chains based on
      this upconversion process that permit the absolute frequency measurement of many
      visible or near-IR possible standards at the 10(-12) accuracy level.
      Transposition of terahertz-scale frequency-difference measurements from the near
      IR to the 10-microm domain is also proposed.

PMID- 19865357
TI  - Generation of compressed 600-720-nm tunable femtosecond pulses by transient
      frequency mixing in a beta-barium borate crystal.
AB  - We demonstrate the feasibility of the compression of tunable pulses by means of
      sum-frequency generation under special group-velocity mismatch conditions. beta
      Barium borate crystal has been shown to support the upconversion process,
      resulting in 160-fs pulses tunable within 600-720 nm when mixing 1.3-ps 1055-nm
      pulses from a Nd:glass laser with 0.95-ps pulses tunable within 1400-2200 nm from
      a traveling-wave parametric generator. A similar compression of ~150-fs
      Ti:sapphire pulses predicted for the sum-frequency tuning range of 520-590 nm.

PMID- 19865358
TI  - Regenerative pulse shaping and amplification of ultrabroadband optical pulses.
AB  - Regenerative pulse shaping is used to alleviate gain narrowing during ultrashort
      pulse amplification. Amplification bandwidths of ~ 100 nm, or nearly three times
      wider than the traditional gain-narrowing limit, are produced with a modified
      Ti:sapphire regenerative amplifier. This novel regenerative amplifier has been
      used to amplify pulses to the 5-mJ level with a bandwidth sufficient to support ~
      10-fs pulses.

PMID- 19865359
TI  - Sigmoid neural transfer function realized by percolation.
AB  - An experiment using the phenomenon of percolation has been conducted to
      demonstrate the implementation of neural functionality (summing and sigmoid
      transfer). A simple analog approximation to digital percolation is implemented.
      The device consists of a piece of amorphous silicon with stochastic bit-stream
      optical inputs, in which a current percolating from one end to the other defines
      the neuron output, also in the form of a stochastic bit stream. Preliminary
      experimental results are presented.

PMID- 19865360
TI  - Frequency-modulation spectroscopy with transform-limited nanosecond laser pulses.
AB  - We demonstrate high-quality FM spectra with nanosecond laser pulses. Transform
      limited pulses with FM sidebands are produced by pulsed amplification of a phase
      modulated cw laser. The pulses can be shifted to the UV by nonlinear mixing. We
      report both initial experiments on I(2) and what is to our knowledge the first
      observation of a far-UV transition by FM spectroscopy, at 214.5 nm. Major
      advantages of this method include (1) spectral resolution of the order of 0.001
      cm(-1), (2) better-defined optical phase, and (3) a much smaller and more easily
      detected modulation frequency, ~500 MHz. The absorption sensitivity is ~10(-4),
      and considerable further improvement is expected.

PMID- 19865361
TI  - Grating interferometer for flatness testing.
AB  - Two diffraction gratings placed in front of a f lat surface generate an
      interference pattern representing the surface deformations. The interference
      pattern is achromatic and has an equivalent wavelength between 4 and 40 microm,
      depending on the grating frequencies and the viewing angle. Using phase-shifting
      techniques, the grating interferometer provides high-precision profile
      measurements of both smooth and rough surfaces.

PMID- 19865362
TI  - Four-port fiber frequency shifter with a null taper coupler: erratum.

PMID- 19865363
TI  - Talbot array illuminators with optimum compression ratio.
AB  - We describe Talbot array illuminators that generate, at fractions of the Talbot
      distance, arrays of bright spots with optimum compression ratio. We compare the
      performance of these Talbot array illuminators with that of an array of parabolic
      lenses.

PMID- 19865364
TI  - Nonglobal model for a near-field scanning optical microscope using diffraction of
      the optical near field.
AB  - Diffraction of the localized optical near field by a subwavelength-sized probe
      (metallic circular aperture) is studied by a nonglobal approach. The problem is
      closely relevant to the basic principle of a near-field scanning optical
      microscope (NSOM). We obtain analytic expressions of the diffracted far field
      from which the transfer function of the NSOM can be calculated. In particular, we
      find a resonance enhancement in the detection efficiency when the sample size is
      similar to the probe size. By lateral scanning of the aperture position at a
      constant height, we also obtain a NSOM image of a dielectric sphere sample.

PMID- 19865365
TI  - Radiative coupling between photonic paint layers.
AB  - Intense isotropic laser emission from an optically pumped scattering gain medium
      has been used to induce isotropic lasing in an adjacent scattering gain medium at
      a longer wavelength. The energy-transfer mechanism between the media involved has
      been studied with a simple model based on radiation-transfer theory. The
      applications of this effect for wavelength-domain coding are also discussed.

PMID- 19865366
TI  - Lanthanum-modified lead zirconate titanate ceramic wafer-based electro-optic
      dynamic diverging lens.
AB  - We present a lanthanum-modified lead zirconate titanate (PLZT) ceramic wafer
      based electro-optic dynamic diverging lens. A quadratic refractive-index
      modulation is induced by application of a linearly changing electrical field
      inside a f lat PLZT wafer. The design offers a simple and compact structure that
      produces a smooth phase modulation distribution. A fabricated dynamic lens of 2
      mm x 2 mm demonstrates a continuous variable focal length from infinity with no
      applied voltage to negative 0.77 m with a voltage of 400 V.

PMID- 19865368
TI  - Tunable stimulated Raman scattering by pumping with Bessel beams.
AB  - We report on a novel pumping scheme for stimulated Raman scattering (SRS) that
      uses a Bessel beam. We have used this scheme for SRS from molecular vibrations in
      acetone and from a polariton mode in a LiIO(3) crystal. A nearly diffraction
      limited Stokes beam was observed along the cone axis of the Bessel beam. The
      generation mechanism of the Stokes beam is identified as being due to
      noncollinear scattering of the component plane waves that constitute the Bessel
      beam. Frequency tuning of SRS from polaritons in LiIO(3) by variation of the
      Bessel beam cone angle is demonstrated.

PMID- 19865367
TI  - Surface-plasmon-enhanced third-harmonic generation in thin silver films.
AB  - Optical third-harmonic generation (THG) is dipole allowed. I report a 10(3)
      signal enhancement of THG that is due to the excitation of a surface plasmon in
      thin silver films by an attenuated-total-internal-ref lection geometry. Because
      the THG signal depends on the cube of the incident intensity and the second
      harmonic generation depends on the square of the intensity, the THG overtakes the
      second-harmonic generation at laser intensities beyond 6 x 10(11) W/cm(2).

PMID- 19865369
TI  - Long-wavelength first hyperpolarizability measurements by hyper-Rayleigh
      scattering.
AB  - A hyper-Rayleigh scattering (HRS) system based on an optical parametric power
      oscillator is described. The first hyperpolarizability, beta, of Crystal Violet
      dye was measured at 1450 and 1500 nm. The resonance-free beta value, beta(0), for
      this octupole was found to be comparable with that of the dipolar dye Disperse
      Red 1 but with the nonlinearity-transparency trade-off worse for the octupole.
      The discrepancy in beta(0) with that reported previously is explained in terms of
      resonance and the adequacy of the octupolar three-state model. The possibility of
      dye aggregation by solvent-dependent HRS is investigated.

PMID- 19865370
TI  - Second-harmonic generation from chalcopyrite-structure semiconductor thin films.
AB  - We propose that thin films of tetragonal chalcopyrite-structure semiconductor
      media are promising nonlinearoptical (NLO) materials for the following reasons:
      Phase matching is possible with them in principle, they can be utilized in a
      waveguide geometry, and they are compatible with III-V substrates. We investigate
      the second-order NLO properties of chalcopyrite-structure CuInSe(2) and CuGaSe(2)
      thin films grown on GaAs(001), using optical second-harmonic (SH) generation at a
      fundamental wavelength of 790 nm. The SH intensities produced by approximately
      stoichiometric CuInSe(2) and CuGaSe(2) thin films are similar to that of GaAs.
      The second-order optical nonlinearities are strongly curtailed in
      nonstoichiometric thin films.

PMID- 19865371
TI  - Spatiotemporal dynamics of self-pumped phase conjugation in a photorefractive
      crystal: multipattern storage using incremental recording.
AB  - We investigate the spatiotemporal dynamics of self-pumped phase conjugation for
      superimposed incrementally recorded images. Experimental evidence of time delay
      in the appearance of phase-conjugation patterns was observed during both the
      recording and the readout phases.

PMID- 19865372
TI  - Bright temporal solitonlike pulses in self-defocusing AlGaAs waveguides near 800
      nm.
AB  - We report the experimental observation of bright temporal solitonlike pulses
      propagating in a material with a negative nonlinearity and positive (normal)
      dispersion. We believe this to be the first observation of bright solitonic
      pulses in a material with a negative Kerr nonlinearity. We have observed a
      gradual narrowing of the output pulse width as a function of increasing input
      power, and our results agree well with simulations.

PMID- 19865373
TI  - Lasing behavior in a liquid spherical dye laser containing highly scattering
      nanoparticles.
AB  - With the addition of scattering nanoparticles to dye-doped spherical droplets,
      lasing has been observed with well-defined thresholds in input-output data. One
      order or more magnitude enhancement of peak intensity from droplet emission has
      been obtained with certain (optimum) additive scattering particles compared with
      nonadditive scattering particles (neat dye-doped droplets). Characteristics of
      input-output intensities, emission spectra (with wavelength shifts), and spectral
      linewidths are reported experimentally, depending on additive quantities of
      scattering nanoparticles.

PMID- 19865374
TI  - Efficient laser operation with nearly diffraction-limited output from a diode
      pumped heavily Nd-doped multimode fiber.
AB  - Laser performance of a diode-pumped Nd-doped multimode phosphate-glass fiber is
      reported. The selection of the fundamental mode in a multimode fiber is
      demonstrated, resulting in laser emission that is close to diffraction limited
      and that is nearly independent of the pump power. The heavily Nd-doped fibers
      with core diameters of 100 microm and lengths between 13 and 32 mm deliver as
      much as 130 mW of cw output power at 1.053 microm. A total efficiency of 31% with
      respect to launched pump power has been achieved.

PMID- 19865375
TI  - Observation of gain in an optically pumped surface-normal multiple-quantum-well
      optical amplifier.
AB  - An optically pumped surface-normal optical amplifier with a 100-period
      InGaAs/InGaAlAs multiple quantum well is fabricated, and a signal gain exceeding
      2 dB is observed for what we believe to be the first time. A laser diode with the
      wavelength lambda of 1.45 microm is used for pumping. An optical single-pass gain
      as high as 2.4 dB is obtained at lambda = 1.585 microm with 65-mW pumping (spot
      diameter 12 microm).

PMID- 19865377
TI  - Phase recovery from the bispectrum aided by the error-reduction algorithm.
AB  - An essential step in bispectral imaging is the recovery of the object's Fourier
      phase from the bispectral phase. Such reconstruction can be performed by
      recursive or least-squares (minimization) methods. It is generally accepted that
      least-squares methods perform better because of their higher noise tolerance. Two
      weighted least-squares minimization schemes are compared, and the use of the
      error-reduction algorithm is suggested as a way to overcome the stagnation at
      local minima common to minimization problems.

PMID- 19865376
TI  - Random phase encoding of composite fully complex filters.
AB  - The mapping of complex-valued functions onto phase-only spatial light modulators
      is examined. Random phase encoding effectively adds amplitude control to the
      phase-only filter and can be used to trade off systematic errors of the phase
      only filter for random errors. This is illustrated for the problem of recognizing
      a threedimensional object from arbitrary views. The complex-valued composite
      filters that constitute a filter bank design are encoded by phase-only and
      pseudorandom methods. The best recognition probabilities are achieved by blending
      the two methods so that only the smallest amplitudes are randomly encoded.

PMID- 19865378
TI  - Parallel optical image addition and subtraction in a dynamic photorefractive
      memory by phase-code multiplexing.
AB  - We propose and demonstrate experimentally a method for utilizing a dynamic phase
      encoded photorefractive memory to realize parallel optical addition, subtraction,
      and inversion operations of stored images. The phase-encoded holographic memory
      is realized in photorefractive BaTiO(3), storing eight images using Walsh
      Hadamard binary phase codes and an incremental recording procedure. By
      subsampling the set of reference beams during the recall operation, the
      selectivity of the phase address is decreased, allowing one to combine images in
      such a way that different linear combination of the images can be realized at the
      output of the memory.

PMID- 19865379
TI  - Fractional Hilbert transform.
AB  - We have generalized the Hilbert transform by defining the fractional Hilbert
      transform (FHT) operation. In the first stage, two different approaches for
      defining the FHT are suggested. One is based on modifying only the spatial
      filter, and the other proposes using the fractional Fourier plane for filtering.
      In the second stage, the two definitions are combined into a fractional Hilbert
      transform, which is characterized by two parameters. Computer simulations are
      presented.

PMID- 19865380
TI  - Data compression in frequency-selective materials using frequency-swept
      excitation pulses.
AB  - We demonstrate the temporal compression of photon echoes in frequency-selective
      materials by application of frequency-swept excitation pulses. Experimental
      results in Pr(3+):Y(2)SiO(5) for two- and three-pulse photon echoes are presented
      and compared with theory. A possible application to temporal reduction of optical
      data streams is shown.

PMID- 19865381
TI  - Signal-to-noise ratio improvement by stochastic resonance in a unidirectional
      photorefractive ring resonator.
AB  - All-optical signal-to-noise ratio improvements by stochastic resonance have been
      obtained by use of the intensity bistability of a unidirectional photorefractive
      ring resonator. A signal-to-noise ratio gain of 10.5 dB has been obtained with a
      near-unity signal-to-noise ratio input signal at 6 mHz.

PMID- 19865382
TI  - Multiply loaded magneto-optical trap.
AB  - We report a two-chambered, differentially pumped system that permits rapid
      collection of trapped atoms with a vapor cell magneto-optical trap (MOT) and
      efficient transfer of these atoms to a second MOT in a lowerpressure chamber.
      During the transfer the atoms are guided down a long, thin tube by a magnetic
      potential, with 90(15%) transfer efficiency. By multiply loading, we accumulate
      and hold as many as 30 times the number collected by the vapor cell MOT. By thus
      separating the collection and holding functions of a MOT, we can collect as many
      as 1.5(0.6) x 10(10) rubidium atoms and hold them for longer than 100 s, using
      inexpensive low-power diode lasers.

PMID- 19865383
TI  - Orthogonal photorefractive grating storage.
AB  - Using multiple signal beams and controlling their relative phases, we demonstrate
      angular multiplexing of phase-sensitive holographic gratings in a photorefractive
      crystal. Interference between diffracted signal beams determines total diffracted
      intensities as a function of the relative phases between input signals compared
      with those between gratings. Complete constructive and destructive interference
      produce maximum and near-zero diffraction, respectively, from orthogonal
      gratings.

PMID- 19865384
TI  - Bending vibration measurement on rotors by laser vibrometry.
AB  - A new technique is proposed for noncontact measurement of bending vibration
      directly from a rotating component. This notoriously difficult and previously
      unattained measurement is a further development of laser Doppler vibrometry.
      Simultaneously the technique provides an accurate measure of shaft torsional
      vibration in situations in which measurements of torsional vibration have shown
      significant sensitivity to bending vibration. Experimental results validate the
      theory developed, and a conservative estimate of the minimum measurable bending
      vibration is made at 20 millidegrees.

PMID- 19865385
TI  - Filtering behavior of a self-induced three-mirror cavity formed by intracavity
      wave mixing in a saturable absorber.
AB  - Wave mixing with a self-induced grating in a saturable absorber, which is
      inserted into a resonator, gives special filtering behavior. In a linear Fabry
      Perot cavity with gain, the grating forms a self-matched, threemirror laser
      cavity that can discriminate between modes whose frequency difference is much
      lower than the grating bandwidth. The effect was used to obtain single-mode
      lasers with narrow linewidths. The selfinduced grating can dynamically adjust
      itself to small disturbances and changes in the cavity parameters.

PMID- 19865386
TI  - All-fiber three-path Mach-Zehnder interferometer.
AB  - We report the realization of a three-path Mach-Zehnder interferometer using
      single-mode fibers and two integrated 3 x 3 fiber couplers. We observed enhanced
      phase sensitivity, as compared with two-path interferometers, with a visibility
      of the interference pattern of more than 97%. This interferometer has an analog
      in two-photon interferometry, and we believe it to be the first nontrivial
      example of N x N multiport interferometers.

PMID- 19865387
TI  - Optical power filter: a new kind of passive nonlinear-optical device.
AB  - We show the possibility of a new kind of passive nonlinear-optical device: an
      optical power filter made of graded-index single-mode fiber (SMF) and a nonlinear
      medium (NLM). It is shown that, only for a particular power, the mode in the SMF
      matches the mode in the NLM. The transmission coefficient from the NLM to the SMF
      is determined, and it is shown that a laser beam with a particular power can be
      filtered out.

PMID- 19865388
TI  - Dipole-on-dielectric model for infrared lithographic spiral antennas.
AB  - We present a dipole-on-dielectric model for lithographic antennas used for
      bolometer coupling in the infrared. The predicted antenna patterns show good
      agreement with measurements of Au-on-Si spiral antennas at 9.5-microm wavelength.
      Angle- and polarization-resolved measurements are proposed, which will further
      probe the behavior of these antenna structures and facilitate refinement of the
      analytical models.

PMID- 19865389
TI  - Effect of an annular pupil on confocal imaging through highly scattering media.
AB  - We report on confocal scanning imaging through highly scattering media. Various
      practical effects including those of the annular pupils and the size of the
      confocal pinhole as well as of the numerical aperture of objectives on the image
      quality are examined xperimentally. The combination of an annular objective with
      a finitesized detector may prove advantageous for improving image quality.

PMID- 19865390
TI  - Soliton-repulsion logic gate.
AB  - We present numerical simulations of a logic gate based on repulsive interaction
      in a dual-core fiber and call it a soliton-repulsion logic gate (SRLG). The
      operation of the SRLG is compared with that of the conventional soliton-dragging
      logic gate based on cross-phase modulation. The length of the SRLG can be reduced
      by a factor of 3 over that of the conventional logic gate. By optimizing
      parameters, terahertz operation can be obtained.

PMID- 19865391
TI  - Optical parametric oscillator incoherent spectroscopy.
AB  - A new incoherent Kerr shutter is demonstrated. It utilizes nanosecond optical
      pulses from an optical parametric oscillator (OPO) that has a broad bandwidth.
      Through the use of abeta-BaB(2)O(4) crystal, the OPO has a coherence time of 60
      800 fs and shows wide wavelength tunability from 410 to 2600 nm. Kerr relaxation
      time constants for CS(2) and nitrobenzene are the same as those cited in previous
      works. We also show, for the first time to our knowledge, a 100-fs response for a
      nitrobenzene solution of 4-(N,N-diethylamino)-beta-nitrostyrene at a 740-nm idler
      wavelength.

PMID- 19865392
TI  - Exact solution to four-wave mixing with complex couplings: reflection geometry.
AB  - An exact solution to photorefractive four-wave mixing equations with complex
      couplings in ref lection geometry is obtained. It is shown that the efficiency of
      the process of phase conjugation can be enhanced by introduction of a frequency
      shift between the pumps and the signal, similar to the case of transmission
      geometry. However, to obtain an improved agreement with experiment, the inclusion
      of transverse effects is found to be necessary.

PMID- 19865393
TI  - Two-dimensional steady-state photorefractive screening solitons.
AB  - We study experimentally steady-state photorefractive screening solitons trapped
      in both transverse dimensionsand measure their beam profiles as they propagate
      throughout the crystal. The solitons are observed to be axially symmetric, and
      they self-bend. We characterize the soliton dependence on the optical intensity,
      appliedelectric-field strength, and beam diameter.

PMID- 19865394
TI  - Averaged pulse dynamics in a cascaded transmission system with passive dispersion
      compensation.
AB  - A theory of optical pulse propagation in cascaded transmission systems that are
      based on the dispersioncompensatingfiber technique is developed. The existence of
      two scales associated with fiber dispersion and system residual dispersion leads
      to a simple model for the averaged pulse dynamics. In the particular case of
      practical importance, the averaged pulse dynamics is governed by the nonlinear
      Schrodinger equation. The pulse transmission stability is examined.

PMID- 19865395
TI  - Nonlinear-optical amplifier based on a dual-core fiber.
AB  - We propose a scheme for all-optical amplification based on a nonlinear-optical
      coupler in which one core is amplifying while another is attenuating. In this
      scheme the input signal is fed into the amplifying core, from where the output is
      also obtained. A weak input easily couples to the lossy core and gets dissipated
      in it, whereas a stronger signal stays and undergoes a nearly linear
      amplification in the active core. When it is used for reshaping pulses in a long
      transmission line, this scheme should allow the pulses to be amplified while
      simultaneously suppressing the noises between them. Simulating equations for the
      cw signal in this model, we are able to find a regime that provides for a strong
      contrast between the suppression of weak signals and amplification of strong ones
      as well as a steep transition from suppression to amplification at a
      certainthreshold.

PMID- 19865396
TI  - Measurement of the refractive-index modulation generated by electrostriction
      induced acoustic waves in optical fibers.
AB  - The refractive-index modulation generated in optical fibers by electrostriction
      induced acoustic waves is investigated directly by a pump-probe measurement
      technique in a 1-km-long fiber Sagnac-loop interferometer. Pump pulses
      propagating unidirectionally around the loop generate transverse acoustic waves
      that produce a time-dependent relative phase shift for the probe pulses. The
      consequent interferometer transmission changes are used as a measure of the
      acoustic interaction. The acoustic impulse response function of the fiber is
      measured by use of short optical pulses with a 1-MHz repetition rate. The
      response consists of a series of peaks separated by ~21 ns with a maximum value
      of refractive-index modulation of -1.1 x 10(-11) generated by the 230-pJ pump
      pulses. At a higher pulse repetition rate of 100 MHz additional temporal
      structure is generated in the 0-5-ns period after the pump pulse, leading to a
      response similar to that observed in longrange soliton interaction.

PMID- 19865397
TI  - Long-period fiber-grating-based gain equalizers.
AB  - Long-period fiber gratings are used to f latten the gain spectrum of erbium-doped
      fiber amplifiers. A broadband amplifier with <0.2-dB gain variation over 30 nm is
      presented. We also show that a chain of amplifiers can be equalized, leading to a
      bandwidth enhancement by a factor of 3.

PMID- 19865398
TI  - Reduction of soliton interactions by sliding-frequency second-order Butterworth
      filters.
AB  - The reduction of the soliton interaction by use of optical sliding-frequency
      second-order Butterworth filters is studied numerically. It is found that the
      second-order Butterworth filters can reduce the soliton interaction more
      effectively than Fabry-Perot filters or third-order Butterworth filters because
      the secondorder Butterworth filter induces larger frequency chirping on the
      soliton, compressing it as it propagates in the fiber after the filter.

PMID- 19865399
TI  - Use of radio-frequency-pulse surface acoustic wave profilometry for passband
      engineering of acousto-optic tunable filters.
AB  - One can determine the acoustic profile of an acousto-optic tunable filter (AOTF)
      either by measuring the intensity of a laser diffracted off the surface of an
      AOTF by the surface acoustic wave (SAW) or by measuring the optical output power
      of an AOTF as a short burst of rf energy is launched down the device. This rf
      burst technique (also called pulse probing) is compared with the established
      optical diffraction SAW profilometry technique. We demonstrate the usefulness of
      rf-burst profilometry to measure the acousto-optic coupling as a function of
      position along an AOTF interaction region. Such a probe can be used to make
      adjustments to the acousto-optic coupling in real time to achieve passband shape
      modification in complex AOTF structures.

PMID- 19865400
TI  - Infrared waveguiding in Si(1-x-y)Ge(x)C(y) upon silicon.
AB  - Polarization-independent waveguiding at 1.32 and 1.54 microm was observed in
      single-crystal S(1-x-y)Ge(x)C(y) grown nearly lattice matched upon Si(100) by
      chemical vapor deposition. Losses were <5 dB/cm at 1.54 microm. Experiments
      indicate that the band gap of three SiGeC alloy waveguides was in the 0.93-0.99
      eV range, in agreement with theory.

PMID- 19865401
TI  - Photodegradation of near-infrared-pumped Tm(3+)-doped ZBLAN fiber upconversion
      lasers.
AB  - Photodegradation has been observed in Tm(3+)-doped ZBLAN fiber lasers pumped with
      laser diodes at 1135 nm. After upconversion lasing at 482 nm, the fiber develops
      color centers that absorb strongly at wavelengths below ~650 nm, affecting
      further upconversion lasing. The rate of damage formation is strongly dependent
      on the pump power level and on the thulium concentration. The color centers are
      bleached by intense blue light but recover with thermal excitation and can be
      removed by thermal annealing at temperature near 100 degrees C.

PMID- 19865402
TI  - Polarization switching in quantum-well vertical-cavity surface-emitting lasers.
AB  - Switching between linearly polarized states of slightly different optical
      frequencies with the same transversemode pattern is found, as the injection
      current is increased. Switchings found here for semiconductor rateequation models
      incorporating a vector electric field, birefringence, and the alpha factor are
      similar to previously reported experimental results.

PMID- 19865403
TI  - Cavity-dumped femtosecond Kerr-lens mode locking in a chromium-doped forsterite
      laser.
AB  - We report the operation of a cavity-dumped self-mode-locked chromium-doped
      forsterite laser with pulse energies exceeding 30 nJ and pulse durations as short
      as 54 fs (FWHM) at 1260 nm. By frequency doubling in a beta-barium borate
      crystal, pulse energies as high as 3 nJ and pulse durations as short as 49 fs
      (FWHM) at 630 nm were generated. The high stability and ultrashort pulse widths
      with a variable repetition rate in both the infrared (1260 nm) and the red (630
      nm) make this system an attractive light source for ultrafast spectroscopy.

PMID- 19865404
TI  - Picosecond optical bistability in metallophthalocyanine-doped polymer film
      waveguides.
AB  - Ultrafast optical bistability was observed in a planar optical waveguide made
      with a 2,9,16,23-tetraoctadecanoylamido-substituted vanadyl phthalocyanine-doped
      polystyrene film. Input-output curves with hysteresis characteristics were
      measured with laser pulses of 60-ps pulse width at 532 nm. The switchup and
      switchdown times were less than 10 and 20 ps, respectively. The origin of the
      nonlinearity giving rise to optical bistability was predominantly electronic
      effects.

PMID- 19865405
TI  - 10-fs pulse generation from a unidirectional Kerr-lens mode-locked Ti:sapphire
      ring laser.
AB  - For the first time to our knowledge, nearly bandwidth-limited 10-fs laser pulses
      centered at 790 nm are generated in a Ti:sapphire ring resonator. Intracavity
      dispersion control is provided by dispersive dielectric mirrors together with the
      insertion of small amounts of intracavity glass path. Mode locking is self
      starting without the use of an aperture.

PMID- 19865406
TI  - Scale-adapted wavelet transform.
AB  - A modified wavelet transform, the scale-adapted wavelet transform (SAWT), is
      proposed. The scale factor is adaptively changed according to the local structure
      of the input signal. The transformed image keeps the same dimensions as the input
      signal without losing the meaningful multiresolution representation. Some simple
      applications of the SAWT are discussed.

PMID- 19865407
TI  - Large angular dispersion by a virtually imaged phased array and its application
      to a wavelength demultiplexer.
AB  - A new scheme that shows large angular dispersion is proposed and demonstrated.
      The key idea to this method is a virtually imaged phased array (VIPA). The
      angular dispersion of a VIPA is 10-20 times larger than those of common
      diffraction gratings, which have blaze angles of ~30 deg. With the VIPA,
      wavelength demultiplexing for 10 channels with 0.8-nm spacing is achieved. Low
      polarization-state dependence (~0.1 dB) is also confirmed.

PMID- 19865408
TI  - Enhanced backscattering of partially coherent light.
AB  - The backscattering enhancement of light from random media is analyzed for
      situations in which the scatterers are illuminated with spatially partially
      coherent light. The effect of coherence is incorporated into the existing
      theories by use of the angular correlation description for the illuminating light
      field. When the area of illumination is infinite, an analogy to the van Cittert
      Zernike theorem leads to the expression for the intensity distribution that is
      given by the sum of backscattered intensities, each of which would arise from
      each incident plane-wave component of the angular spectrum. It is shown that the
      backscattering cone is partially suppressed and deformed owing to breaking of the
      time-reversal symmetry of mutiple-scattering paths.

PMID- 19865409
TI  - Synthesis of large optical delays by mode coupling in electro-optically tunable
      TE-TM mode converters.
AB  - We report on a device capable of generating long optical path differences through
      the use of a combination of a tunable TE-TM converter and a phase shifter. The
      values that are achievable (~4 mm) are approximately three times higher than
      those obtained with integrated imbalanced Mach-Zehnder interferometers, with the
      additional advantage of low optical losses.

PMID- 19865410
TI  - Two-mirror beam-shaping technique for high-power diode bars.
AB  - A simple beam-shaping technique is described whereby the output from a highly
      asymmetric non-diffractionlimited laser source, such as a high-power diode bar,
      can be reconfigured with nearly equal beam-quality factors in orthogonal planes
      and without a significant reduction in brightness. Using this technique, in
      conjunction with conventional lenses, we have focused the output from a 20-W cw
      diode bar to a very intense, nearly circular spot with a 1/e(2) beam diameter of
      ~100 microm and a far-field beam divergence (half-angle) of ~0.2 rad.

PMID- 19865411
TI  - Self-imaging of discrete gratings at fractions of the Talbot distance: an
      eigenvalue problem.
AB  - Using a matrix formulation of Fresnel diffraction, we describe discrete gratings
      that exhibit self-images at fractions of the Talbot distance. Such structures are
      obtained as solutions of an eigenvalue equation.

PMID- 19865412
TI  - Stimulated Raman scattering in hydrogen by frequency-doubled amplified
      femtosecond Ti:sapphire laser pulses.
AB  - We present results on stimulated Raman scattering in hydrogen excited by 200-fs
      duration 1-kHz repetitionrate and 0.6-W average-power Ti:sapphire (780-nm) and
      0.2-W average-power second-harmonic (390-nm) laser pulses with linear and
      circular polarizations. Spectral and temporal measurements of the vibrational and
      rotational components at Stokes and anti-Stokes frequencies in the wavelength
      range of 289-1154 nm are reported. We observe threefold shortening of the first
      vibrational Stokes component pulses, excited by 400-fsduration second-harmonic
      pulses.

PMID- 19865413
TI  - Method for nulling nonrandom timing jitter in soliton transmission.
AB  - The shift in pulse arrival times stemming from several important sources is not
      truly random but rather shows a high degree of correlation from one pulse to the
      next. Such jitter sources include the acoustic effect, solitons-soliton
      collisions in wavelength-division multiplexing, and the tendency of fiber
      birefringence to convert collision-induced polarization scattering into time
      shifts. Moving the acceptance window of a timedivision demultiplexer in
      approximate synchronism with the correlated time shifts effectively removes their
      potential for creating errors.

PMID- 19865414
TI  - Optical response of a nonlinear absorbing dielectric film.
AB  - The transmittance, the absorptance, and the phase shift on transmission and on
      ref lection of a nonlinear, absorbing dielectric film are studied numerically for
      various model nonlinearities. The solution of the coupled nonlinear differential
      equations is straightforward.

PMID- 19865415
TI  - Highly efficient green-light generation by quasi-phase-matched frequency doubling
      of picosecond pulses from an amplified mode-locked Nd:YLF laser.
AB  - We report on first-order quasi-phase-matched frequency doubling of picosecond
      pulses to the green, using a sample of periodically poled lithium niobate. In cw
      mode-locked operation, 330 mW of average green power was generated with an
      average conversion efficiency of ~52%. With a quasi-cw mode-locked pulse train an
      average conversion efficiency of ~65% was achieved, and 1.3 W of green power
      (average power within the 10-micros pulse envelope) was produced. At these powers
      there was no significant photorefractive damage, as confirmed by measured M(2)
      beam-quality factors of ~1.1 for both output fundamental and second-harmonic
      beams.

PMID- 19865416
TI  - Experimental investigation of resonant enhancement of the acoustic interaction of
      optical pulses in an optical fiber.
AB  - The acoustic interaction of optical pulses in optical fibers is investigated
      directly by time-resolved pump-probe measurements of the transmission of a fiber
      Sagnac-loop interferometer. Resonant enhancement of the refractive-index change
      deltan(ac) induced by the acoustic waves is observed when the repetition
      frequency of the pulse train is close to a vibrational eigenfrequency of the
      fiber. For standard fiber deltan(ac) is enhanced by a factor of ~3 at the 465-MHz
      eigenmode frequency, and this factor increases to ~10 when the polymer jacket is
      removed from the fiber. The guided acoustic wave Brillouin scattering spectrum
      that arises from spontaneous thermal excitation of the acoustic eigenmodes of the
      fibers is also measured. The results suggest that the resonant enhancement of
      deltan(ac) is limited by dampling that is due to the polymer jacket and by
      inhomogeneous broadening that is due to fiber diameter variations.

PMID- 19865417
TI  - Pseudo-phase-matched four-wave mixing in soliton wavelength-division multiplexing
      transmission.
AB  - In a soliton transmission system using lumped amplifiers, pseudo phase matching
      allows four-wave mixing fields from soliton-soliton collisions to grow
      uncontrollably and inf lict severe penalties. Through numerical simulation, we
      show that this growth can be eliminated, or at least greatly reduced, through the
      use of fiber whose dispersion is tapered, either continuously or in steps, in
      conformity with the fiber loss curve.

PMID- 19865418
TI  - Refractometers and tunable components based on side-polished fibers with
      multimode overlay waveguides: role of the superstrate.
AB  - A normal mode analysis is applied to the investigation of the role of the
      superstrate in terms of its refractive index and thickness in estimating the
      performance of fiber refractometers and the tunability of fiber components based
      on evanescent coupling of a side-polished fiber to a multimode overlay waveguide.
      The model is shown to yield a complete transfer function and information about
      all the major characteristics of such in-line fiber devices. The results closely
      match the trends of the reported experiments.

PMID- 19865419
TI  - Timing jitter in soliton transmission with sliding filters.
AB  - We show that the coupling between amplitude and frequency f luctuations that is
      due to filter sliding significantly enhances timing jitter in soliton
      transmission controlled by in-line filters. This is the likely reason for the
      extra timing jitter observed in a recent soliton transmission experiment using
      sliding filters.

PMID- 19865420
TI  - Passively Q-switched 180-ps Nd:LaSc(3)(BO(3))(4) microchip laser.
AB  - We passively Q switched a Nd:LaSc(3)(BO(3))(4) microchip laser with an
      antiresonant Fabry-Perot saturable absorber (A-FPSA) and achieved single
      frequency, 180-ps pulses with 0.1 microJ of pulse energy at a repetition rate of
      110 kHz. Because of the compactness and scaling possibilities offered by the A
      FPSA, the pulse width can be varied from 180 ps to 30 ns and the repetition rate
      from 50 kHz to 7 MHz.

PMID- 19865421
TI  - Self-photopumped neonlike x-ray laser.
AB  - We propose a new x-ray laser mechanism that uses radiation from the strongest 3d
      ? 2p Ne-like resonance line in an optically thick plasma to radiatively drive
      population from the Ne-like ground state to the 3d state, which then lases to two
      3p states. Collisional mixing of the 3p states with nearby 3s and 3d states
      depopulates the lower laser states. Modeling is presented for this mechanism in
      Ne-like Ar, and in experiments we observe one potential 3d ? 3p lasing transition
      at 45.1 nm in Ne-like Ar.

PMID- 19865422
TI  - Mode hopping in external-cavity diode lasers.
AB  - Mode hopping in external-cavity AlGaAs diode lasers has been studied
      experimentally. Its dependence on the amount of feedback and the external-cavity
      round-trip phase has been studied. The results are compared with the predictions
      of potential well models. As the feedback is increased the results differ
      considerably from this theory. A qualitative treatment is also presented.

PMID- 19865423
TI  - Aberration-free stretcher design for ultrashort-pulse amplification.
AB  - A novel aberration-free pulse stretcher design is presented. This system permits
      the stretching of a 30-fs pulse to 300 ps and recompression to a duration of 33
      fs, limited by the spectral clipping.

PMID- 19865424
TI  - Femtosecond measurement of high-order harmonic pulse width and electron
      recombination time by field ionization.
AB  - We measured the ultrashort XUV pulse width by the pump-probe method, using
      femtosecond dynamics of field ionization. We measured the pulse width of the
      ninth harmonic (88.3 nm) of a Ti:sapphire laser, using the difference of the
      absorption cross section between Kr and Kr(+). The change of transmission of the
      ninth harmonic for the delay between the pump and the probe pulses gives both the
      pulse width of the ninth harmonic and the recombination time of Kr(+). The
      measured pulse width of the ninth harmonic was 260 fs. The recombination time of
      Kr(+) was ~2 ps, which does not contradict the estimated time of the threebody
      recombination.

PMID- 19865425
TI  - Bragg-assisted parametric amplification of short optical pulses.
AB  - Parametric amplification of pulses in Bragg gratings is investigated numerically.
      Gain is observed for a much larger range of parameters than in uniform media.
      This is explained in terms of grating-assisted phase matching. In contrast to
      that for cw results, the input signal pulse need not be tuned to a particular
      frequency. Rather, through cross-phase modulation the signal self-locks to the
      correct frequency for growth.

PMID- 19865426
TI  - Restoration of images degraded by atmospheric turbulence by a least-squares
      method and a Markov process.
AB  - We present a two-step deconvolution method for restoring images degraded by
      atmospheric turbulence. The first step is linear space-invariant filtering, and
      the second step is a nonhomogeneous Markov process. This nonhomogeneous method
      preserves the discontinuities of the original image better than the homogeneous
      method does.

PMID- 19865427
TI  - Photon-gated photoconductivity of Pr(3+):YAG.
AB  - We have observed photon-gated photoconductivity in Pr:YAG, providing clear
      evidence for photoionization of the trivalent praseodymium ion in the solid
      state. Photoionization occurs by two-step absorption from (3)H(4)(1) ? (1)D(2)(1)
      followed by an excited-state absorption from (1)D(2) to the lowest component of
      the 4f5d configuration. The excitation spectrum of the photocurrent shows sharp
      (1)D(2) spectral features, providing unambiguous assignment of the photocurrent.

PMID- 19865428
TI  - Red-band holographic storage in azo dye sensitized by noncoherent light.
AB  - Biphoton holographic storage recorded with 633-nm He-Ne beams has been
      investigated in Methyl Yellowdoped polystyrene film sensitized by weak
      noncoherent light from a low-pressure Hg lamp. It is demonstrated that the
      holography in the sample is erasable without fading. The dynamic behavior of the
      hologram is dependent on the cis-trans isomerization by noncoherent light and 633
      nm beams and photoinduced heat.

PMID- 19865429
TI  - Shift-multiplexed holographic memory using the two-lambda method.
AB  - We present theoretical and experimental results on the application of the two
      lambda method for prolonged readout of holographic memories to shift multiplexing
      implemented with a spherical-wave reference beam.

PMID- 19865431
TI  - Folded Jamin interferometer: a stable instrument for refractive-index
      measurements.
AB  - A novel two-beam interferometer for the measurement of a refractive index or its
      induced changes is described. This interferometer consists of only two optical
      elements and is largely insensitive to their movement. A laboratory prototype has
      been built. It uses a polarized version of the folded Jamin interferometer to
      allow for convenient phase adjustment.

PMID- 19865430
TI  - Stellar scintillations as a remote atmospheric wave-front sensor.
AB  - Stellar scintillations are considered noise in adaptive-optics sensors and are
      measured for calibration purposes only. We propose to use scintillations to
      provide direct instantaneous information about the structure of the atmosphere.
      As a result it will be possible to increase the field of view provided by
      adaptive optics. The scintillation pattern is created when stellar light is
      diffracted by high-altitude turbulence. Alternatively, this pattern can be viewed
      as a Laplacian of this turbulence and can thus be inverted to estimate it. The
      measurement is limited by the intensity and the angular size of the reference
      star, by the height distribution of the atmospheric turbulence, and by the
      detector resolution and spectral response.

PMID- 19865433
TI  - Fiber-optic distributed sensing by a two-loop Sagnac interferometer.
AB  - A two-loop Sagnac interferometer is proposed for fiber-optic distributed sensing.
      The location of a disturbance can be determined from the two output phase signals
      of the two Sagnac loops, and the amplitude of the disturbance can be obtained by
      integration of the phase signal. A prototype distributed impact sensing system
      has been tested based on the two-loop Sagnac interferometer.

PMID- 19865432
TI  - Polarization interferometer for measuring the flying height of magnetic read
      write heads.
AB  - Traditional optical flying-height testers use only the normal-incidence
      reflectivity of the interface between the read-write slider and a glass disk
      surrogate. We propose a tester that fully analyzes the complex amplitude ref
      lectivity of the interface, including the polarization-dependent complex phase.
      The new approach is more accurate and repeatable and has no loss of precision at
      zero flying height. Further, the same instrument directly measures the complex
      index of refraction for the slider material in situ, obviating the need for a
      separate metrology step with an ellipsometer.

PMID- 19865434
TI  - Optical intensity mapping on the nanometer scale by near-field photodetection
      optical microscopy.
AB  - Near-field photodetection optical microscopy (NPOM) is a fundamentally new
      approach to near-field optical microscopy. This scanning-probe technique uses a
      nanometer-scale photodiode detector as a near-field optical probe. We have
      fabricated probes for NPOM that have optically sensitive areas as small as 100 nm
      x 100 nm. These new NPOM probes have been employed to image light transmitted
      through holes in an aluminum film. Near-surface optical interference is observed
      near defects and edges of the aluminum film. The optical edge response is shown
      to be of the order of 100 nm.

PMID- 19865435
TI  - Time-resolved studies of stimulated emission from colloidal dye solutions.
AB  - The temporal profiles of the emission from titania particle suspensions in
      Rhodamine 640 perchlorate dye solutions excited by 10-ps pulses of 527-nm
      radiation were measured over a wide range of particle and dye concentrations and
      laser powers. The dynamics of stimulated emission from random media is modeled by
      a random walk of photons within the colloid and rate equations for molecular
      excitations. The pulse width and the dependence of the threshold for laser action
      on dye and scatter concentration are computed by a Monte Carlo simulation of the
      model and are found to be in qualitative agreement with experiment.

PMID- 19865436
TI  - Ultimate Q of optical microsphere resonators.
AB  - We demonstrate the quality factor Q - (0.8 +/- 0.1) x 10(10) of whispering
      gallery modes in fused-silica microspheres at 633 nm, close to the ultimate level
      determined by fundamental material attenuation as measured in optical fibers. The
      lifetime of ultimate Q is limited by adsorption of atmospheric water. Monitoring
      of adsorption kinetics with submonolayer sensitivity by Q factors and frequencies
      of whispering-gallery modes is demonstrated. The possibility of supermaterial Q's
      owing to intrinsic suppression of scattering losses in micropheres is discussed.

PMID- 19865437
TI  - Dark beams with a constant notch.
AB  - Dark beams are wave fields carrying information in dark regions. We
      experimentally demonstrate dark beams that maintain a constant notch shape and
      size along a predetermined domain in free space. The energy is concentrated
      around the dark region with negligible sidelobes. These beams are generated with
      low-information-content phase-only diffractive elements in an on-axis
      configuration.

PMID- 19865439
TI  - Stability of black solitons in media with arbitrary nonlinearity.
AB  - It is shown that the black solitons in an optical fiber or a uniform medium with
      arbitrary nonlinearity are all stable. The conclusion from the analytical
      stability analysis is consistent with that of numerical simulations. This then
      dismisses a previous criterion that suggests that the black solitons in a
      saturable nonlinear medium can be unstable.

PMID- 19865438
TI  - Compensating for dispersion and the nonlinear Kerr effect without phase
      conjugation.
AB  - We propose the use of a dispersive medium with a negative nonlinear refractive
      index coefficient as a way to compensate for the dispersion and the nonlinear
      effects resulting from pulse propagation in an optical fiber. The undoing of
      pulse interaction might allow for increased bit rates.

PMID- 19865440
TI  - Stabilizing dark solitons by periodic phase-sensitive amplification.
AB  - We show that dark solitons are stabilized with respect to amplitude variations
      when phase-sensitive amplification and spectral filtering are used in combination
      to compensate for linear loss. In particular, we show that spectral filtering
      inhibits the sideband instabilities typical of nonlinear pulses and cw waves in
      periodically amplified systems, whereas phase-sensitive amplification inhibits
      the destabilization of the constant-intensity background wave caused by the
      filtering.

PMID- 19865442
TI  - Dynamics of distributed-feedback fiber lasers: effect of nonlinear refraction.
AB  - We present a model for the dynamics of distributed-feedback fiber lasers that
      includes the effect of nonlinear refraction. The model predicts antiphase and in
      phase self-pulsations, asymmetric output, and deterministic chaos if the
      nonlinear refractive index of the fiber material is sufficiently large. Self
      pulsations with frequencies of tens to hundreds of megahertz and pulse widths of
      several nanoseconds are observed in computer simulations.

PMID- 19865441
TI  - Effect of poling conditions on second-harmonic generation in fused silica.
AB  - A systematic study of the effects of poling time and applied voltage on second
      harmonic (SH) generation in thermally poled silica glass reveals that the SH
      signal is proportional to the square of the applied voltage and that the speed of
      the poling process increases with the applied voltage. Prior treatment of the
      samples is found to affect the poling process, and the optimum poling conditions
      are observed to depend on the poling atmosphere. The mechanism of thermal poling
      is discussed in the light of these new results.

PMID- 19865443
TI  - Single-mode operation in symmetric planar waveguides using isotropic chiral
      media.
AB  - We present the dispersion relations for symmetric planar waveguides in general
      isotropic media. The planar waveguide structure that utilizes chiral media in the
      cladding regions is emphasized. Unlike other symmetric planar waveguide
      configurations in isotropic media, this structure possesses a nondegenerate
      lowest-order mode. Therefore symmetric planar waveguides using chiral cladding
      materials can support single-mode operation.

PMID- 19865444
TI  - Low-threshold diode-pumped femtosecond Cr(3+):LiSrAlF(6) laser.
AB  - Routes toward minimizing the self-mode-locking threshold of an all-solid-state
      diode-laser-pumped Cr(3+):LiSrAlF(6) laser are considered. Sub-100-fs-duration
      pulses have been generated at pump powers below 100 mW by exploitation of a low
      astigmatism cavity configuration in conjunction with a high-brightness self
      injection-locked semiconductor laser pump module.

PMID- 19865445
TI  - 69-W-average-power Yb:YAG laser.
AB  - We report what is to our knowledge the highest quasi-cw output power to date, 150
      W, with average output power of 69 W and pulse energy of 250 mJ, for an InGaAs
      diode-pumped Yb:YAG laser. This performance was obtained by use of a laser head
      designed to be part of a master oscillator power amplifier operating at 3 kW.

PMID- 19865446
TI  - Converting light into spectrally pure microwave oscillation.
AB  - We present theoretical and experimental results for a novel oscillator that
      converts continuous light energy into stable and spectrally pure microwave
      signals. This optoelectronic oscillator can generate ultrastable spectrally pure
      microwave reference frequencies as high as 75 GHz with a phase noise lower than
      2140 dBcyHz at 10 kHz, independent of oscillation frequency.

PMID- 19865447
TI  - All-in-one dispersion-compensating saturable absorber mirror for compact
      femtosecond laser sources.
AB  - A molecular-beam-epitaxy-grown semiconductor saturable absorber mirror with
      integrated dispersion compensation, based on a Gires-Tournois structure, is
      demonstrated. This dispersion-compensating saturable absorber mirror generated
      160-fs pulses with 25-mW average power from a simple diode-pumped Cr:LiSrAlF(6)
      laser without any additional dispersion compensation.

PMID- 19865448
TI  - Low-threshold operation of an ultrashort-pulse mode-locked Ti:sapphire laser.
AB  - We demonstrate low-pump-power operation of a self-mode-locked Ti:sapphire laser.
      Stable, sub-20-fs duration pulses, with output powers of 35-100 mW, were obtained
      for pump powers in the range of 400 mW-1 W. Our design uses a tight focusing
      geometry for both the argon-ion and Ti:sapphire beams within the Ti:sapphire
      crystal, which significantly reduces the pump-power requirements.

PMID- 19865449
TI  - Second-order nonlinearities of polycrystalline molecular films studied on a 20-fs
      time scale.
AB  - Second-harmonic generation in polycrystalline pentacene films of submicrometer
      thickness by pulses of 18-fs duration is studied. We observe a second-order
      nonlinearity of as much as d(eff) = 0.045 pm/V, which is resonantly enhanced at
      wavelengths near 790 nm. Off-resonance autocorrelation studies demonstrate a
      quasiinstantaneous nonlinear response of the material, whereas experiments on
      resonance point to a finite response time T(2) of the order of 15 fs.

PMID- 19865450
TI  - Optimal detection of a target with random gray levels on a spatially disjoint
      background noise.
AB  - We describe a pattern-recognition processor that is optimal for detection and
      location of a target with white Gaussian random gray levels on a white random
      spatially disjoint background. We show that this algorithm consists of
      correlations of the silhouette of the reference object with preprocessed versions
      of the scene image. This result can provide a theoretical basis for pattern
      recognition techniques that use nonlinear preprocessing of images before
      correlation.

PMID- 19865451
TI  - Color pattern recognition with circular component whitening.
AB  - Polychromatic object recognition based on circular whitening preprocessing of red
      green-blue components and multichannel matched filtering is described. Computer
      simulations and experimental results are provided to facilitate recognizing a
      color target among objects of similar shape but with different color contents.
      Experimental results are obtained with an optical correlator with two spatial
      light modulators, one to introduce the scene and the second one to introduce the
      filter.

PMID- 19865452
TI  - Direct reconstruction of surfaces from near-field intensity under spatially
      incoherent illumination.
AB  - We solve the inverse scattering problem for a surface profile by measuring the
      intensity of the scattered near field. It was shown numerically [Opt. Lett. 20,
      949 (1995)] that the image produced by the superposition of different images
      taken with all possible angles of incidence closely follows the surface profile.
      We establish a rigorous analysis of this method based on perturbation theory.
      Furthermore, we prove that the procedure is equivalent to illuminating the
      surface with incoherent light and thus has broad experimental applications.

PMID- 19865453
TI  - Form birefringence dispersion in periodic layered media.
AB  - We analyze the form birefringence dispersion of periodic dielectric layered
      media. Using Bloch wave analysis, we investigate the shape of the normal surface
      and its dependence on wavelength. Our higher-order uniaxial approximation gives
      an explicit expression for the additional dispersion of the form birefringence
      that is due to the finite layer thickness.

PMID- 19865454
TI  - Two-dimensional photonic band-gap structures as quasi-metals.
AB  - By considering waves that propagate out of the transverse plane, we show that
      common high-index materials (e.g., GaAs) with a two-dimensional array of air
      holes can act in some ways as three-dimensional photonic band-gap structures. In
      particular, we describe a dielectric quasi-metal that ref lects all propagating
      light incident from free space.

PMID- 19865455
TI  - Waveform-decomposition-based algorithm for horizontal parallax-only-display
      computer-generated holograms.
AB  - A fast algorithm to compute a scattering pattern produced by a two-dimensional
      object is presented. Rather than by use of an approximation, this algorithm is
      derived by decomposition of the spherical nature of a radiation pattern into the
      sum of plane waves. Thus it precludes the phase errors that exist in
      approximationbased Fresnel holograms. Moreover, the amount of computation
      required in this method is shown to be significantly smaller than that of a well
      known ray-tracing method; excellent performance, as good as one could obtain with
      the ray-tracing method, is achieved. Implementation results as well as sampling
      constraints are also presented.

PMID- 19865456
TI  - Characterization of Fresnel holograms by a pixel phase-error function.
AB  - We present what is to our knowledge the first experimental observation of
      controlled intensity f luctuations of Fresnel holograms of 8 microm x 8 microm
      pixel size by using a function for calculation of optical phase errors from the
      pixel area of an aperture of synthetic Fresnel holograms derived without
      approximation.

PMID- 19865457
TI  - Single-substrate birefringent computer-generated holograms.
AB  - A polarization-selective computer-generated hologram fabricated upon a single
      substrate of birefringent YVO(4) crystal is demonstrated. Rigorous couple-wave
      analysis was used to model the element. The experimentally measured first
      diffraction order showed a close-to-theoretically predicted diffraction
      efficiency of 39%. The polarization contrast ratio was measured to be 33:1.

PMID- 19865459
TI  - Method for analysis of the fundamental measuring uncertainty of laser Doppler
      velocimeters.
AB  - A method is presented for analysis of the relationship of the velocity measuring
      uncertainty and the system parameters of laser Doppler velocimeters. The method
      permits optimization of the laser Doppler system to minimize the uncertainty of
      fluid velocity measurements.

PMID- 19865458
TI  - Non-Bragg orders in dynamic self-diffraction on thick phase gratings in a
      photorefractive polymer.
AB  - We demonstrate that recording thick holographic phase gratings in photorefractive
      polymers can lead not only to very efficient Bragg diffraction but also to rather
      strong diffraction into non-Bragg orders. We show that this effect has features
      drastically different from those of Raman-Nath diffraction on thin gratings. We
      compare the experimental results with a model based on the theory of dynamic self
      diffraction in a photorefractive medium. Applications of this effect in devices
      for optical image processing are proposed.

PMID- 19865460
TI  - Two-dimensional temperature determination in sooting flames by filtered Rayleigh
      scattering.
AB  - We present what to our knowledge are the first filtered Rayleigh scattering
      temperature measurements and use them in sooting f lame. This new technique for
      two-dimensional thermography in gas combustion overcomes some of the major
      disadvantages of the standard Rayleigh technique. It suppresses scattered
      background light from walls or windows and permits detection of two-dimensional
      Rayleigh intensity distributions of the gas phase in the presence of small
      particles by spectral filtering of the scattered light.

PMID- 19865461
TI  - Dispersive white-light interferometry for absolute distance measurement with
      dielectric multilayer systems on the target.
AB  - We have extended the use of a dispersive white-light interferometer for absolute
      distance measurement to include effects of dielectric multilayer systems on the
      target. The phase of the ref lected wave changes as a function of wavelength and
      layer thickness and causes errors in the interferometric distance measurement.
      With dispersive white-light interferometry these effects can be measured in situ,
      and the correct mechanical distance can be determined. The effects of thin films
      deposited upon the target have been investigated for one and two layers
      (photoresist and SiO(2) upon Si). Experimental results show that the thicknesses
      of these layers can also be determined with an accuracy of the order of 10 nm.

PMID- 19865462
TI  - Stabilized three-wavelength source calibrated by electronic means for high
      accuracy absolute distance measurement.
AB  - Multiple-wavelength interferometry offers great f lexibility in working distance
      and sensitivity by permitting an appropriate choice of the different wavelengths
      used, and it can be operated on rough surfaces. The accuracy of distance
      measurement with this approach depends on the stability and the calibration of
      the different wavelengths. A novel concept of a multiple-wavelength source that
      uses laser diodes has been developed. It allows one to obtain an absolute
      calibration of the synthetic wavelengths by the use of electronic beat-frequency
      measurements. Experimental results show that a calibration of the synthetic
      wavelength in the millimeter range with an accuracy of better than 10(-5) is
      feasible.

PMID- 19865463
TI  - Optical comb generator as an efficient short-pulse source.
AB  - We demonstrate a novel technique for converting a continuous-wave laser beam into
      a stable train of short pulses with a high repetition rate. The system, which is
      generally applicable, is based on a purely passive coupled-cavity optical
      frequency comb generator, which ensures a high overall efficiency. The repetition
      rate of the device is determined by the drive frequency of an electro-optic
      modulator and the pulse width by the rf power applied to the modulator. We have
      observed pulses down to 3.3 ps long at a 5.34-GHz repetition rate and an overall
      efficiency of 11%. The experimental results for pulse shape and width show
      excellent quantitative agreement with the results of a simple model.

PMID- 19865464
TI  - Optical device with excitatory and inhibitory optical outputs.
AB  - We propose a novel optical device that can produce either an excitatory or an
      inhibitory optical output, depending on the state of the device. The state
      depends on the previous optical input. The device is expected to possess novel
      bistable characteristics useful for implementation of an all-optical neuron.

PMID- 19865465
TI  - Universal grating design for pulse stretching and compression in the 800-1100-nm
      range.
AB  - We have developed a holographically produced master metallic grating that
      achieves >91% diffraction efficiency over the wavelength range 800-1100 nm and a
      maximum diffraction efficiency at 1053 nm greater than 93% when used with TM
      polarization near the Littrow angle. The near-uniform diffraction efficiency with
      laser wavelength makes this design attractive for use in chirped-pulse
      amplification systems employing Ti:sapphire, Cr:LiSAF, or Nd:glass and permits
      high-fidelity stretching and compression of extremely short (10-fs) pulses.

PMID- 19865466
TI  - Scanning single-mode fiber optic catheter-endoscope for optical coherence
      tomography.
AB  - We describe a new optical coherence tomography catheter-endoscope for micrometer
      scale, cross-sectional imaging in internal organ systems. The catheter-endoscope
      uses single-mode fiber optics with a novel transverse scanning design. The distal
      end of the catheter-endoscope uses a gradient-index lens with a microprism to
      emit and collect a single spatial-mode optical beam with specific focusing
      characteristics. The beam is scanned in a circumferential pattern and can image
      transverse cross sections through the structure into which it is inserted. A
      device with a diameter as small as 1.1 mm has been achieved, and imaging of in
      vitro human venous morphology is demonstrated.

PMID- 19865467
TI  - Influence of the scattering phase function on light transport measurements in
      turbid media performed with small source-detector separations.
AB  - Many methods of optical tissue diagnosis require that measurements be performed
      with small source-detector separations in a backscatter geometry. Monte Carlo
      simulations are used to demonstrate that for these situations light transport
      depends on the exact form of the angular scattering probability distribution,
      P(theta). Simulations performed with different forms of P(theta) with the same
      value of ?cos theta? result in the collection of significantly different
      fractions of the incident photons, particularly when small-numerical-aperture
      delivery and collection fibers are employed. More photons are collected for the
      distribution that has a higher probability of scattering events with theta > 125
      degrees . For the clinically relevant optical parameters employed here, the
      differences in light collection are >60%.

PMID- 19865468
TI  - A New Antimalarial Polyether from a Marine Streptomyces sp. H668.
AB  - The antimalarial guided fractionation of the culture of marine Streptomyces sp.
      strain H668 led to the isolation of a new polyether metabolite. The structure was
      determined by comprehensive NMR and MS assignments. This new metabolite showed in
      vitro antimalarial activity against both the chloroquine-susceptible (D6) and 
      resistant (W2) clones of Plasmodium falciparum, without cytotoxicity to normal
      cells (Vero) making it a promising first lead from this marine bacterium.

PMID- 19865469
TI  - A qualitative and quantitative analysis of protein substitution in human burn
      wounds.
AB  - OBJECTIVE: In major burn wounds of more than 15% total burn surface area mediator
      associated reactions lead to capillary leak resulting in critical condition.
      Little is known about the efficiency of protein substitution. We quantified and
      qualified the systemic and local protein loss in burn patients during protein
      substitution, comparing fresh frozen plasma and the human serum protein solution
      Biseko. METHODS: In 40 patients suffering from second-degree burn wounds with the
      total burn surface area between 20% and 60%, immediately after admission a
      defined wound surface area was enclosed with in a wound chamber. Wound fluid and
      serum samples were collected in 8 hour intervals for 2 days. Samples were
      analyzed for total protein, albumin, immunoglobulins -A, -G, -M, clotting
      parameters, c-reactive protein, and white blood cells. Protein substitution
      started 24 hour posttrauma. In a randomized pattern, patients received equal
      volumes of fresh frozen plasma or Biseko. RESULTS: Total protein and albumin
      accumulated in high concentrations in wound fluid. With beginning of fresh frozen
      plasma substitution on day 2 posttrauma, serum total protein (1.7 g-3.9 g) and
      albumin (1.3 g-3.4 g) concentrations increased. Substitution of Biseko resulted
      in a stronger increase (serum total protein 1.8 g to 4.5 g, albumin 0.9 g to 3.4
      g). Wound fluid concentrations revealed similar change patterns. Immunoglobulins
      showed higher serum levels in the Biseko group. C-reactive protein and white
      blood cell values indicated a lower immunological reaction in the Biseko group.
      CONCLUSIONS: Substitution of human protein solutions such as Biseko can result in
      significantly higher serum protein and albumin concentrations as well as lower
      infection parameters. Higher serum immunoglobulins could help to decrease
      potential immunodeficiency.

PMID- 19865478
TI  - Gain in brain immunity in the oldest-old differentiates cognitively normal from
      demented individuals.
AB  - BACKGROUND: Recent findings suggest that Alzheimer's disease (AD)
      neuropathological features (neuritic plaques and NFTs) are not strongly
      associated with dementia in extreme old (over 90 years of age) and compel a
      search for neurobiological indices of dementia in this rapidly growing segment of
      the elderly population. We sought to characterize transcriptional and protein
      profiles of dementia in the oldest-old. METHODS AND FINDINGS: Gene and protein
      expression changes relative to non-demented age-matched controls were assessed by
      two microarray platforms, qPCR and Western blot in different regions of the
      brains of oldest-old and younger old persons who died at mild or severe stages of
      dementia. Our results indicate that: i) consistent with recent neuropathological
      findings, gene expression changes associated with cognitive impairment in oldest
      old persons are distinct from those in cognitively impaired youngest-old persons;
      ii) transcripts affected in young-old subjects with dementia participate in
      biological pathways related to synaptic function and neurotransmission while
      transcripts affected in oldest-old subjects with dementia are associated with
      immune/inflammatory function; iii) upregulation of immune response genes in
      cognitively intact oldest-old subjects and their subsequent downregulation in
      dementia suggests a potential protective role of the brain immune-associated
      system against dementia in the oldest-old; iv) consistent with gene expression
      profiles, protein expression of several selected genes associated with the
      inflammatory/immune system in inferior temporal cortex is significantly increased
      in cognitively intact oldest-old persons relative to cognitively intact young-old
      persons, but impaired in cognitively compromised oldest-old persons relative to
      cognitively intact oldest-old controls. CONCLUSIONS: These results suggest that
      disruption of the robust immune homeostasis that is characteristic of oldest-old
      individuals who avoided dementia may be directly associated with dementia in the
      oldest-old and contrast with the synaptic and neurotransmitter system failures
      that typify dementia in younger old persons.

PMID- 19865479
TI  - The phylogenetics and ecology of the orthopoxviruses endemic to North America.
AB  - The data presented herein support the North American orthopoxviruses (NA OPXV) in
      a sister relationship to all other currently described Orthopoxvirus (OPXV)
      species. This phylogenetic analysis reaffirms the identification of the NA OPXV
      as close relatives of "Old World" (Eurasian and African) OPXV and presents high
      support for deeper nodes within the Chordopoxvirinae family. The natural
      reservoir host(s) for many of the described OPXV species remains unknown although
      a clear virus-host association exists between the genus OPXV and several
      mammalian taxa. The hypothesized host associations and the deep divergence of the
      OPXV/NA OPXV clades depicted in this study may reflect the divergence patterns of
      the mammalian faunas of the Old and New World and reflect a more ancient presence
      of OPXV on what are now the American continents. Genes from the central region of
      the poxvirus genome are generally more conserved than genes from either end of
      the linear genome due to functional constraints imposed on viral replication
      abilities. The relatively slower evolution of these genes may more accurately
      reflect the deeper history among the poxvirus group, allowing for robust
      placement of the NA OPXV within Chordopoxvirinae. Sequence data for nine genes
      were compiled from three NA OPXV strains plus an additional 50 genomes collected
      from Genbank. The current, gene sequence based phylogenetic analysis reaffirms
      the identification of the NA OPXV as the nearest relatives of "Old World" OPXV
      and presents high support for deeper nodes within the Chordopoxvirinae family.
      Additionally, the substantial genetic distances that separate the currently
      described NA OPXV species indicate that it is likely that many more undescribed
      OPXV/NA OPXV species may be circulating among wild animals in North America.

PMID- 19865480
TI  - Dual localized AtHscB involved in iron sulfur protein biogenesis in Arabidopsis.
AB  - BACKGROUND: Iron-sulfur clusters are ubiquitous structures which act as
      prosthetic groups for numerous proteins involved in several fundamental
      biological processes including respiration and photosynthesis. Although simple in
      structure both the assembly and insertion of clusters into apoproteins requires
      complex biochemical pathways involving a diverse set of proteins. In yeast, the J
      type chaperone Jac1 plays a key role in the biogenesis of iron sulfur clusters in
      mitochondria. METHODOLOGY/PRINCIPAL FINDINGS: In this study we demonstrate that
      AtHscB from Arabidopsis can rescue the Jac1 yeast knockout mutant suggesting a
      role for AtHscB in iron sulfur protein biogenesis in plants. In contrast to
      mitochondrial Jac1, AtHscB localizes to both mitochondria and the cytosol. AtHscB
      interacts with AtIscU1, an Isu-like scaffold protein involved in iron-sulfur
      cluster biogenesis, and through this interaction AtIscU1 is most probably
      retained in the cytosol. The chaperone AtHscA can functionally complement the
      yeast Ssq1knockout mutant and its ATPase activity is enhanced by AtHscB and
      AtIscU1. Interestingly, AtHscA is also localized in both mitochondria and the
      cytosol. Furthermore, AtHscB is highly expressed in anthers and trichomes and an
      AtHscB T-DNA insertion mutant shows reduced seed set, a waxless phenotype and
      inappropriate trichome development as well as dramatically reduced activities of
      the iron-sulfur enzymes aconitase and succinate dehydrogenase. CONCLUSIONS: Our
      data suggest that AtHscB together with AtHscA and AtIscU1 plays an important role
      in the biogenesis of iron-sulfur proteins in both mitochondria and the cytosol.

PMID- 19865481
TI  - Genome sequence of the versatile fish pathogen Edwardsiella tarda provides
      insights into its adaptation to broad host ranges and intracellular niches.
AB  - BACKGROUND: Edwardsiella tarda is the etiologic agent of edwardsiellosis, a
      devastating fish disease prevailing in worldwide aquaculture industries. Here we
      describe the complete genome of E. tarda, EIB202, a highly virulent and multi
      drug resistant isolate in China. METHODOLOGY/PRINCIPAL FINDINGS: E. tarda EIB202
      possesses a single chromosome of 3,760,463 base pairs containing 3,486 predicted
      protein coding sequences, 8 ribosomal rRNA operons, and 95 tRNA genes, and a
      43,703 bp conjugative plasmid harboring multi-drug resistant determinants and
      encoding type IV A secretion system components. We identified a full spectrum of
      genetic properties related to its genome plasticity such as repeated sequences,
      insertion sequences, phage-like proteins, integrases, recombinases and genomic
      islands. In addition, analysis also indicated that a substantial proportion of
      the E. tarda genome might be devoted to the growth and survival under diverse
      conditions including intracellular niches, with a large number of aerobic or
      anaerobic respiration-associated proteins, signal transduction proteins as well
      as proteins involved in various stress adaptations. A pool of genes for secretion
      systems, pili formation, nonfimbrial adhesions, invasions and hemagglutinins,
      chondroitinases, hemolysins, iron scavenging systems as well as the incomplete
      flagellar biogenesis might feature its surface structures and pathogenesis in a
      fish body. CONCLUSION/SIGNIFICANCE: Genomic analysis of the bacterium offered
      insights into the phylogeny, metabolism, drug-resistance, stress adaptation, and
      virulence characteristics of this versatile pathogen, which constitutes an
      important first step in understanding the pathogenesis of E. tarda to facilitate
      construction of a practical effective vaccine used for combating fish
      edwardsiellosis.

PMID- 19865482
TI  - Proteome profiling in murine models of multiple sclerosis: identification of
      stage specific markers and culprits for tissue damage.
AB  - The identification of new biomarkers is of high interest for the prediction of
      the disease course and also for the identification of pathomechanisms in multiple
      sclerosis (MS). To specify markers of the chronic disease phase, we performed
      proteome profiling during the later phase of myelin oligodendrocyte glycoprotein
      induced experimental autoimmune encephalomyelitis (MOG-EAE, day 35 after
      immunization) as a model disease mimicking many aspects of secondary progressive
      MS. In comparison to healthy controls, high resolution 2 dimensional gel
      electrophoresis revealed a number of regulated proteins, among them glial
      fibrilary acidic protein (GFAP). Phase specific up-regulation of GFAP in chronic
      EAE was confirmed by western blotting and immunohistochemistry. Protein levels of
      GFAP were also increased in the cerebrospinal fluid of MS patients with
      specificity for the secondary progressive disease phase. In a next step, proteome
      profiling of an EAE model with enhanced degenerative mechanisms revealed
      regulation of alpha-internexin, syntaxin binding protein 1, annexin V and
      glutamate decarboxylase in the ciliary neurotrophic factor (CNTF) knockout mouse.
      The identification of these proteins implicate an increased apoptosis and
      enhanced axonal disintegration and correlate well the described pattern of tissue
      injury in CNTF -/- mice which involve oligodendrocyte (OL) apoptosis and axonal
      injury.In summary, our findings underscore the value of proteome analyses as
      screening method for stage specific biomarkers and for the identification of new
      culprits for tissue damage in chronic autoimmune demyelination.

PMID- 19865483
TI  - Relationships between hematopoiesis and hepatogenesis in the midtrimester fetal
      liver characterized by dynamic transcriptomic and proteomic profiles.
AB  - In fetal hematopoietic organs, the switch from hematopoiesis is hypothesized to
      be a critical time point for organogenesis, but it is not yet evidenced. The
      transient coexistence of hematopoiesis will be useful to understand the
      development of fetal liver (FL) around this time and its relationship to
      hematopoiesis. Here, the temporal and the comparative transcriptomic and
      proteomic profiles were observed during the critical time points corresponding to
      the initiation (E11.5), peak (E14.5), recession (E15.5), and disappearance (3
      ddp) of mouse FL hematopoiesis. We found that E11.5-E14.5 corresponds to a FL
      hematopoietic expansion phase with distinct molecular features, including the
      expression of new transcription factors, many of which are novel KRAB (Kruppel
      associated box)-containing zinc finger proteins. This time period is also
      characterized by extensive depression of some liver functions, especially
      catabolism/utilization, immune and defense, classical complement cascades, and
      intrinsic blood coagulation. Instead, the other liver functions increased, such
      as xenobiotic and sterol metabolism, synthesis of carbohydrate and glycan, the
      alternate and lectin complement cascades and extrinsic blood coagulation, and
      etc. Strikingly, all of the liver functions were significantly increased at E14.5
      E15.5 and thereafter, and the depression of the key pathways attributes to build
      the hematopoietic microenvironment. These findings signal hematopoiesis
      emigration is the key to open the door of liver maturation.

PMID- 19865484
TI  - A unique, consistent identifier for alternatively spliced transcript variants.
AB  - BACKGROUND: As research into alternative splicing reveals the fundamental
      importance of this phenomenon in the genome expression of higher organisms, there
      is an increasing need for a standardized, consistent and unique identifier for
      alternatively spliced isoforms. Such an identifier would be useful to eliminate
      ambiguities in references to gene isoforms, and would allow for the reliable
      comparison of isoforms from different sources (e.g., known genes vs.
      computational predictions). Commonly used identifiers for gene transcripts prove
      to be unsuitable for this purpose. METHODOLOGY: We propose an algorithm to
      compute an isoform signature based on the arrangement of exons and introns in a
      primary transcript. The isoform signature uniquely identifies a transcript
      structure, and can therefore be used as a key in databases of alternatively
      spliced isoforms, or to compare alternative splicing predictions produced by
      different methods. In this paper we present the algorithm to generate isoform
      signatures, we provide some examples of its application, and we describe a web
      based resource to generate isoform signatures and use them in database searches.
      CONCLUSIONS: Isoform signatures are simple, so that they can be easily generated
      and included in publications and databases, but flexible enough to unambiguously
      represent all possible isoform structures, including information about coding
      sequence position and variable transcription start and end sites. We believe that
      the adoption of isoform signatures can help establish a consistent, unambiguous
      nomenclature for alternative splicing isoforms. The system described in this
      paper is freely available at http://genome.ufl.edu/genesig/, and supplementary
      materials can be found at http://genome.ufl.edu/genesig-files/.

PMID- 19865485
TI  - Mice chronically fed high-fat diet have increased mortality and disturbed immune
      response in sepsis.
AB  - BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram
      positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are
      few effective therapies for sepsis, increased basic knowledge about factors
      predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study
      was to study the effect of Western diet on mortality induced by intravenous S.
      aureus inoculation and the immune functions before and after bacterial
      inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks,
      like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality
      during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial
      load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed
      compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels
      and fat mRNA expression of the immune suppressing cytokines interleukin-1
      receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition,
      HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also,
      HFD-fed mice with and without infection had increased levels of macrophages in
      fat. The proportion and function of phagocytosing granulocytes, and the
      production of reactive oxygen species (ROS) by peritoneal lavage cells were
      decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply
      that chronic HFD disturb several innate immune functions in mice, and impairs the
      ability to clear S. aureus and survive sepsis.

PMID- 19865486
TI  - Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi
      Institutional Case-Control Study of Breast Cancer in African-American and
      European-American Women.
AB  - Breast cancer in African-American (AA) women occurs at an earlier age than in
      European-American (EA) women and is more likely to have aggressive features
      associated with poorer prognosis, such as high-grade and negative estrogen
      receptor (ER) status. The mechanisms underlying these differences are unknown. To
      address this, we conducted a case-control study to evaluate risk factors for high
      grade ER- disease in both AA and EA women. With the onset of the Health Insurance
      Portability and Accountability Act of 1996, creative measures were needed to
      adapt case ascertainment and contact procedures to this new environment of
      patient privacy. In this paper, we report on our approach to establishing a
      multicenter study of breast cancer in New York and New Jersey, provide
      preliminary distributions of demographic and pathologic characteristics among
      case and control participants by race, and contrast participation rates by
      approaches to case ascertainment, with discussion of strengths and weaknesses.

PMID- 19865487
TI  - Synthesis and characterization of new Schiff bases derived from N (1)-substituted
      isatin with dithiooxamide and their Co(II), Ni(II), Cu(II), Pd(II), and Pt(IV)
      complexes.
AB  - Three new Schiff bases of N-substituted isatin L(I), L(II,) and L(III) = Schiff
      base of N-acetylisatin, N-benzylisatin, and N-benzoylisatin, respectively, and
      their metal complexes C(1a,b) = [Co(2)(L(I))(2)Cl(3)]Cl, C(2) =
      [Ni(L(I))(2)Cl(2)]0.4BuOH, C(3) = [CuL(I)Cl(H(2)O)]Cl 0.5BuOH, C(4) =
      [Pd(L(I))(2)Cl]Cl, C(5) = [Pt(L(1))(2)Cl(2)]Cl(2) 1.8EtOH.H(2)O, C(6a) =
      [CoL(II)Cl]Cl 0.4H(2)O 0.3DMSO, C(6b) = [CoL(II)Cl]Cl 0.3H(2)O 0.1BuOH, C(7) =
      [NiL(II)Cl(2)], C(8) = [CuL(II)]Cl(2) H(2)O , C(9) = [Pd(L(II))(2)]Cl(2), C(10) =
      [Pt(L(II))(2.5)Cl]Cl(3), C(11a) = [Co(L(III))]C(12) H(2)O, C(11b) =
      [Co(L(III))]Cl(2) 0.2H(2)O, and C(12) = [Ni(L(III))(2)]Cl(2), C(13) =
      [Ni(L(III))(2)]Cl(2) were reported. The complexes were characterized by elemental
      analyses, metal and chloride content, spectroscopic methods, magnetic moments,
      conductivity measurements, and thermal studies. Some of these compounds were
      tested as antibacterial and antifungal agents against Staphylococcus aureus,
      Proteus vulgaris, Candida albicans, and Aspergillus niger.

PMID- 19865488
TI  - Purple sweet potato color ameliorates cognition deficits and attenuates oxidative
      damage and inflammation in aging mouse brain induced by d-galactose.
AB  - Purple sweet potato color (PSPC), a naturally occurring anthocyanin, has a
      powerful antioxidant activity in vitro and in vivo. This study explores whether
      PSPC has the neuroprotective effect on the aging mouse brain induced by D
      galactose (D-gal). The mice administrated with PSPC (100 mg/kg.day, 4 weeks, from
      9th week) via oral gavage showed significantly improved behavior performance in
      the open field and passive avoidance test compared with D-gal-treated mice (500
      mg/kg.day, 8 weeks). We further investigate the mechanism involved in
      neuroprotective effects of PSPC on mouse brain. Interestingly, we found, PSPC
      decreased the expression level of glial fibrillary acidic protein (GFAP),
      inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), inhibited
      nuclear translocation of nuclear factor-kappaB (NF-kappaB), increased the
      activity of copper/zinc superoxide dismutase (Cu/Zn-SOD) and catalase (CAT), and
      reduced the content of malondialdehyde (MDA), respectively. Our data suggested
      that PSPC attenuated D-gal-induced cognitive impairment partly via enhancing the
      antioxidant and anti-inflammatory capacity.

PMID- 19865490
TI  - Investigation of the miR16-1 (C > T) + 7 Substitution in Seven Different Types of
      Cancer from Three Ethnic Groups.
AB  - Background. MicroRNAs are a type of small noncoding RNA molecules that have been
      shown to control gene expression in eukaryotes. Aberrant expression and
      alteration of miRNAs may be responsible for human diseases including cancer. An
      miR16-1 (C > T) + 7 gene mutation has been previously found in familial chronic
      lymphocytic leukemia patients, one of which reported a family history of breast
      cancer. miR16-1 regulates the expression of bcl-2, which is important in
      retinoblastoma, and is located in a genomic region that is frequently lost in
      nasopharyngeal and hepatocellular carcinomas (HCCs). Therefore, miR16-1 may be
      potentially important in the etiology of several solid tumors. To understand the
      power of the miR16-1 (C > T) + 7 mutation as a prognostic and diagnostic risk
      factor, we investigated the mutation in patients with seven different types of
      cancer including 188 with breast, 102 with ovarian, and 22 nasopharyngeal
      carcinomas, 96 HCC, 872 chronic myeloid leukemia (CML), 39 chronic lymphocytic
      leukemia (CLL), and 46 retinoblastoma cases from three different ethnic groups
      and of hereditary and sporadic etiology. Methods. 5'Nuclease TaqMan SNP
      genotyping assay was used to detect the miR16-1 gene C > T substitution. Results.
      The miR16-1 (C > T) + 7 substitution was not detected in any of the groups
      studied. Conclusions. Considering the large scale of our study, the
      representation of different ethnicities and levels of hereditary risk, we
      conclude that the miR-16-1 (C > T) + 7 mutation is not a good diagnostic or
      prognostic indicator of risk for the cancers tested.

PMID- 19865491
TI  - Mirror writing and a dissociative identity disorder.
AB  - Individuals with dissociative identity disorder (DID) have been known to show
      varied skills and talents as they change from one dissociative state to another.
      For example, case reports have described people who have changed their handedness
      or have spoken foreign languages during their dissociative states. During an
      interview with a patient with DID, a surprising talent emerged when she wrote a
      sentence for the Folstein Mini-Mental State Exam-mirror writing. It is not known
      whether her mirror writing had a deeper level of meaning; however, it does
      emphasize the idiosyncratic nature of dissociative identity disorder.

PMID- 19865492
TI  - Effect of resistance training on hematological blood markers in older men and
      women: a pilot study.
AB  - The aim of this study was to examine the effects of resistance training on
      hematological blood markers in older individuals. Twenty-nine men and women
      participated to this study. Subjects were randomized in 2 groups: (1) control (n
      = 13) and (2) resistance training (n = 16). At baseline and after the
      intervention, subjects were submitted to a blood sample to determine their
      hematological profile (red blood cells, hemoglobin, hematocrit, platelets,
      leukocytes, neutrophils, lymphocytes, monocytes, mean corpuscular volume, mean
      corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell
      distribution width). At baseline, no difference was observed between groups.
      Moreover, we found no significant difference after the intervention on any of
      these markers. A 6-month resistance program in healthy older individuals seems to
      have no beneficial nor deleterious effects on hematological blood parameters.
      However, resistance training was well tolerated and should be recommended for
      other health purposes. Further studies are needed to confirm these results in a
      large population.

PMID- 19865493
TI  - Assessment of shock wave lithotripters via cavitation potential.
AB  - A method to characterize shock wave lithotripters by examining the potential for
      cavitation associated with the lithotripter shock wave (LSW) has been developed.
      The method uses the maximum radius achieved by a bubble subjected to a LSW as a
      representation of the cavitation potential for that region in the lithotripter.
      It is found that the maximum radius is determined by the work done on a bubble by
      the LSW. The method is used to characterize two reflectors: an ellipsoidal
      reflector and an ellipsoidal reflector with an insert. The results show that the
      use of an insert reduced the -6 dB volume (with respect to peak positive
      pressure) from 1.6 to 0.4 cm(3), the -6 dB volume (with respect to peak negative
      pressure) from 14.5 to 8.3 cm(3), and reduced the volume characterized by high
      cavitation potential (i.e., regions characterized by bubbles with radii larger
      than 429 um) from 103 to 26 cm(3). Thus, the insert is an effective way to
      localize the potentially damaging effects of shock wave lithotripsy, and suggests
      an approach to optimize the shape of the reflector.

PMID- 19865494
TI  - Influence of viscosity on the scattering of an air pressure wave by a rigid body:
      a regular boundary integral formulation.
AB  - This paper gives a regular vector boundary integral equation for solving the
      problem of viscous scattering of a pressure wave by a rigid body. Firstly, single
      layer viscous potentials and a generalized stress tensor are introduced.
      Correspondingly, generalized viscous double-layer potentials are defined. By
      representing the scattered field as a combination of a single-layer viscous
      potential and a generalized viscous double-layer potential, the problem is
      reduced to the solution of a vectorial Fredholm integral equation of the second
      kind. Generally, the vector integral equation is singular. However, there is a
      particular stress tensor, called pseudostress, which yields a regular integral
      equation. In this case, the Fredholm alternative applies and permits a direct
      proof of the existence and uniqueness of the solution. The results presented here
      provide the foundation for a numerical solution procedure.

PMID- 19865495
TI  - Global Governmental Investment in Nanotechnologies.
AB  - Nanotechnologies seem to have huge potential to bring benefits in areas as
      diverse as drug development, water decontamination, information and communication
      infrastructures, and the production of stronger, lighter and perfect
      nanomaterials. This potential attracts global investment from governments and
      private sectors in nanotechnologies with the hopes that R&D and commercial
      applications of nanomaterials, nanodevices, nanoparticles and nanodrugs will
      provide new impetus, after the ebb-tides of biotechnology and dotcom, to turn
      faltering economies around. The global governmental funding has been actively
      promoting industrial and academic cooperation to realize big prosperity from the
      nanotechnologies. This article summarizes historic trends and status of global
      governmental supports for nanotechnologies.

PMID- 19865496
TI  - Introduction of a Novel Swine-Origin Influenza A (H1N1) Virus into Milwaukee,
      Wisconsin in 2009.
AB  - On 17 April 2009, novel swine origin influenza A virus (S-OIV) cases appeared
      within the United States. Most influenza A diagnostic assays currently utilized
      in local clinical laboratories do not allow definitive subtype determination.
      Detailed subtype analysis of influenza A positive samples in our laboratory
      allowed early confirmation of a large outbreak of S-OIV in southeastern Wisconsin
      (SEW). The initial case of S-OIV in SEW was detected on 28 April 2009. All
      influenza A samples obtained during the 16 week period prior to 28 April 2009,
      and the first four weeks of the subsequent epidemic were sub typed. Four
      different multiplex assays were employed, utilizing real time PCR and end point
      PCR to fully subtype human and animal influenza viral components. Specific
      detection of S-OIV was developed within days. Data regarding patient demographics
      and other concurrently circulating viruses were analyzed. During the first four
      weeks of the epidemic, 679 of 3726 (18.2%) adults and children tested for
      influenza A were identified with S-OIV infection. Thirteen patients (0.34%)
      tested positive for seasonal human subtypes of influenza A during the first two
      weeks and none in the subsequent 2 weeks of the epidemic. Parainfluenza viruses
      were the most prevalent seasonal viral agents circulating during the epidemic (of
      those tested), with detection rates of 12% followed by influenza B and RSV at
      1.9% and 0.9% respectively. S-OIV was confirmed on day 2 of instituting subtype
      testing and within 4 days of report of national cases of S-OIV. Novel surge
      capacity diagnostic infrastructure exists in many specialty and research
      laboratories around the world. The capacity for broader influenza A sub typing at
      the local laboratory level allows timely and accurate detection of novel strains
      as they emerge in the community, despite the presence of other circulating
      viruses producing identical illness. This is likely to become increasingly
      important given the need for appropriate subtype driven anti-viral therapy and
      the potential shortage of such medications in a large epidemic.

PMID- 19865497
TI  - Complete mechanical characterization of soft media using nonspherical rods.
AB  - Hydrogels have been used as substrates for studying the cellular processes by
      many researchers. The stiffness of such gels was also characterized previously.
      However, in most of the cases, these soft Poisson's ratio was assumed
      incompressible and Poisson's ratio is assumed to be one-half. This may not be
      true in many cases, and might alter the calculation of the stiffness of the gels.
      In this study, we present equations for the complete characterization of soft
      media, i.e., calculation of Young's modulus, shear modulus, and Poisson's ratio.
      The method involves the individual measurement of either the displacement or
      rotation of cylindrical rods embedded in the soft media, under the application of
      an external force or torque. Equations involving shear modulus and Poisson's
      ratio for rotation of the rod and Young's modulus and Poisson's ratio for the
      displacement of the rod are independently derived. In addition, the displacement
      and rotation of the rods embedded in an elastic medium, under the application of
      either a force or a torque, respectively, were also calculated using finite
      element analysis. These values compared well with the displacements and rotations
      obtained using closed form equations.

PMID- 19865498
TI  - Piezoelectric properties of domain engineered barium titanate single crystals
      with different volume fractions of domain walls.
AB  - A piezoelectric domain wall model has been developed to analyze the effective
      piezoelectric properties of domain engineered BaTiO(3) (BT) single crystals with
      different volume fractions of 90 degrees domain walls. The model takes into
      account the nonuniform deformation in the domain wall region, which can create
      additional anisotropy to enhanced functional properties of multidomain single
      crystals. Our theoretical results indicate that a larger volume fraction of
      domain walls will produce larger effective piezoelectric coefficients. In
      addition, with the increase in domain wall volume fraction, [011](c) poled BT
      single crystals will have a much larger piezoelectric property enhancement than
      [111](c) poled BT single crystals.

PMID- 19865499
TI  - Circumcision with the plastibell device in hooded prepuce or glanular
      hypospadias.
AB  - PURPOSE: To retrospectively review our experience in infants with glanular
      hypospadias or hooded prepuce without meatal anomaly, who underwent circumcision
      with the plastibell device. Although circumcision with the plastibell device is
      well described, there are no reported experiences pertaining to hooded prepuce or
      glanular hypospadias that have been operated on by this technique. MATERIALS AND
      METHODS: Between September 2002 and September 2008, 21 children with hooded
      prepuce (age 1 to 11 months, mean 4.6 months) were referred for hypospadias
      repair. Four of them did not have meatal anomaly. Their parents accepted this
      small anomaly and requested circumcision without glanuloplasty. In all cases, the
      circumcision was corrected by a plastibell device. RESULTS: No complications
      occurred in the circumcised patients, except delayed falling of bell in one case
      that was removed by a surgeon, after the tenth day. CONCLUSION: Circumcision with
      the plastibell device is a suitable method for excision of hooded prepuce. It can
      also be used successfully in infants, who have miniglanular hypospadias, and
      whose parents accepted this small anomaly.

PMID- 19865500
TI  - Accelerating best care at baylor dallas.
AB  - A culture of quality improvement (QI) is needed to bridge the gap between
      possible STEEEP (safe, timely, effective, efficient, equitable, and patient
      centered) care and actual usual care. Baylor Health Care System (BHCS) developed
      Accelerating Best Care at Baylor (ABC Baylor), an innovative educational program
      that teaches health care leaders the theory and techniques of rapid-cycle QI.
      Course participants learn general principles of continuous QI, as well as health
      care-specific QI techniques, and finish the course by designing and implementing
      their own QI project. ABC Baylor has been employed in a variety of settings and
      has spread its success to other organizations, especially small and rural
      hospitals. These hospitals, like BHCS, have demonstrated sustained improvements
      that are due in part to the use of ABC Baylor and its reliance on specific
      modules that focus on health care safety, service, equity, and chronic disease
      management. The role of ABC Baylor training and consulting is part of the overall
      culture and infrastructure that have allowed BHCS to achieve success in its
      improvement journey, including the receipt of several national awards and the
      achievement of high reliability in compliance with Centers for Medicare and
      Medicaid Services core measures of processes of care related to heart failure,
      acute myocardial infarction, community-acquired pneumonia, and surgical care. The
      culture of rapid-cycle QI facilitated by ABC Baylor serves to link BHCS's vision
      and goals to practical execution.

PMID- 19865501
TI  - Clinical strategies for supporting the untransfusable hemorrhaging patient.
AB  - Hemorrhaging patients who cannot be transfused due to personal beliefs or the
      lack of compatible blood products provide a unique challenge for clinicians. Here
      we describe a 58-year-old African American man with a history of sickle cell
      beta(+) thalassemia who had recently received a multiunit exchange transfusion
      and developed hematochezia followed by severe anemia. Due to the presence of
      multiple alloantibodies, no compatible packed red blood cell (pRBC) units could
      initially be located. The patient was managed with mechanical ventilation,
      colloid and crystalloid solutions, procoagulants, and recombinant erythropoietin.
      After an extensive search by our blood bank, enough compatible pRBC units were
      identified and the patient survived without significant clinical sequelae.
      Management of the untransfusable hemorrhaging patient requires a multidisciplined
      approach, with coordination between blood banks, hematologists, intensivists, and
      other specialists. Steps should be taken to avoid or limit blood loss, identify
      compatible pRBC units, control hypotension, maximize oxygen delivery, minimize
      metabolic demand, and stimulate erythropoiesis. In dire circumstances, use of
      experimental hemoglobin substitutes or transfusion of the least serologically
      incompatible pRBCs available may be considered.

PMID- 19865502
TI  - Surgical management of mandibular condylar hyperplasia type 1.
AB  - This study compared outcomes of two surgical methods for patients diagnosed with
      active condylar hyperplasia type 1. Group 1 (n = 12) was treated with
      orthognathic surgery only, while group 2 (n = 42) was treated with high
      condylectomies, articular disc repositioning, and orthognathic surgery. There was
      no statistically significant difference between the two groups for maximum
      incisal opening, lateral excursions, and subjective jaw function before surgery.
      Group 2 showed more active presurgical mandibular growth (P < 0.05). At long-term
      follow up, no differences were found in lateral excursions and subjective jaw
      function. Group 2 showed a greater increase in maximum incisal opening (P < 0.01)
      and stability (P < 0.05) at long-term follow-up. All of the patients in group 1
      grew back into skeletal and occlusal Class III relationships requiring secondary
      intervention, whereas all patients in group 2 remained stable in a Class I
      skeletal and occlusal relationship. Thus, patients with active condylar
      hyperplasia treated with high condylectomy, articular disc repositioning, and
      orthognathic surgery had stable, predictable outcomes compared with those treated
      with orthognathic surgery only. The high condylectomy effectively arrests
      disproportionate mandibular growth while maintaining normal jaw function.

PMID- 19865503
TI  - Obstruction of the celiac axis resulting in a pancreaticoduodenal artery
      aneurysm.
AB  - A 47-year-old woman complained of abdominal pain, and a computed tomography scan
      indicated compressive obstruction of the celiac axis and a 4-cm retropancreatic
      aneurysm. An angiogram identified the aneurysmal vessel as the posterior
      pancreaticoduodenal artery. All foregut structures were supplied by this
      aneurysmal vessel. Via an open approach, the inflow and outflow of the aneurysm
      were ligated, and blood flow to the celiac axis was reconstructed via a bypass
      from the supraceliac aorta. A follow-up scan indicated complete thrombosis of the
      aneurysm. The patient is now symptom free. Open reconstruction of the celiac axis
      is mandatory when ligation of a pancreaticoduodenal aneurysm results in foregut
      ischemia. Ligation and reconstruction can be done safely and effectively in the
      elective setting.

PMID- 19865504
TI  - Embolization of an intracranial dural arteriovenous fistula using ultrasound
      guided puncture of a pericranial venous pouch.
AB  - Endovascular treatment of intracranial dural arteriovenous fistulas can be very
      challenging. Conventional endovascular treatment approaches include transarterial
      or transvenous access from the common femoral artery or vein, respectively. A
      novel approach is described for endovascular treatment of an aggressive type 4
      dural arteriovenous fistula. This patient, who had recently suffered an
      associated intracranial hemorrhage, harbored a dural arteriovenous fistula
      involving his transverse dural venous sinus that did not allow for conventional
      transarterial or transvenous embolization routes. The clinical history and
      technical details are provided.

PMID- 19865505
TI  - Sudden atrial fibrillation associated with acute alcohol ingestion and cor
      triatriatum.

PMID- 19865506
TI  - Sinus of Valsalva aneurysm.

PMID- 19865507
TI  - Celebrities and substance abuse.

PMID- 19865508
TI  - Happy birthday, Gray's Anatomy.

PMID- 19865509
TI  - Osler under 40.

PMID- 19865510
TI  - Bachelors in Baltimore: mr. Mencken and dr. Welch.

PMID- 19865511
TI  - Daniel Angel Savino, MD: a conversation with the editor.

PMID- 19865512
TI  - Design optimization of piezoresistive cantilevers for force sensing in air and
      water.
AB  - Piezoresistive cantilevers fabricated from doped silicon or metal films are
      commonly used for force, topography, and chemical sensing at the micro- and
      macroscales. Proper design is required to optimize the achievable resolution by
      maximizing sensitivity while simultaneously minimizing the integrated noise over
      the bandwidth of interest. Existing analytical design methods are insufficient
      for modeling complex dopant profiles, design constraints, and nonlinear phenomena
      such as damping in fluid. Here we present an optimization method based on an
      analytical piezoresistive cantilever model. We use an existing iterative
      optimizer to minimimize a performance goal, such as minimum detectable force. The
      design tool is available as open source software. Optimal cantilever design and
      performance are found to strongly depend on the measurement bandwidth and the
      constraints applied. We discuss results for silicon piezoresistors fabricated by
      epitaxy and diffusion, but the method can be applied to any dopant profile or
      material which can be modeled in a similar fashion or extended to other
      microelectromechanical systems.

PMID- 19865513
TI  - Chemical interactions and their role in the microphase separation of block
      copolymer thin films.
AB  - The thermodynamics of self-assembling systems are discussed in terms of the
      chemical interactions and the intermolecular forces between species. It is clear
      that there are both theoretical and practical limitations on the dimensions and
      the structural regularity of these systems. These considerations are made with
      reference to the microphase separation that occurs in block copolymer (BCP)
      systems. BCP systems self-assemble via a thermodynamic driven process where
      chemical dis-affinity between the blocks driving them part is balanced by a
      restorative force deriving from the chemical bond between the blocks. These
      systems are attracting much interest because of their possible role in
      nanoelectronic fabrication. This form of self-assembly can obtain highly regular
      nanopatterns in certain circumstances where the orientation and alignment of
      chemically distinct blocks can be guided through molecular interactions between
      the polymer and the surrounding interfaces. However, for this to be possible,
      great care must be taken to properly engineer the interactions between the
      surfaces and the polymer blocks. The optimum methods of structure directing are
      chemical pre-patterning (defining regions on the substrate of different
      chemistry) and graphoepitaxy (topographical alignment) but both centre on
      generating alignment through favourable chemical interactions. As in all self
      assembling systems, the problems of defect formation must be considered and the
      origin of defects in these systems is explored. It is argued that in these
      nanostructures equilibrium defects are relatively few and largely originate from
      kinetic effects arising during film growth. Many defects also arise from the
      confinement of the systems when they are 'directed' by topography. The potential
      applications of these materials in electronics are discussed.

PMID- 19865514
TI  - Antioxidant and cytotoxic activities of Centella asiatica (L) Urb.
AB  - In the present study, the phenolic (Folin-Dennis) and flavonoid (colorimetric
      assay) constituents, antioxidant [2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH)
      assay] and cytotoxic activities of an aqueous extract (AE) of Centella asiatica
      leaves were investigated. The aqueous extract (50 g/L) was obtained by infusion
      followed by cold maceration for 24 h. The levels of phenolic and flavonoid
      compounds were 2.86 g/100 g and 0.361 g/100 g, respectively. The AE showed
      elevated DPPH scavenging activity, with an IC(50) value of 31.25 microg/mL. The
      AE had a promising activity against mouse melanoma (B(16)F(1)), human breast
      cancer (MDA MB-231) and rat glioma (C(6)) cell lines, with IC(50) values of
      698.0, 648.0 and 1000.0 microg/mL, respectively. A positive correlation was
      established between the level of flavonoids, antioxidant and antitumor
      activities.

PMID- 19865515
TI  - Biodegradability of plastics.
AB  - Plastic is a broad name given to different polymers with high molecular weight,
      which can be degraded by various processes. However, considering their abundance
      in the environment and their specificity in attacking plastics, biodegradation of
      plastics by microorganisms and enzymes seems to be the most effective process.
      When plastics are used as substrates for microorganisms, evaluation of their
      biodegradability should not only be based on their chemical structure, but also
      on their physical properties (melting point, glass transition temperature,
      crystallinity, storage modulus etc.). In this review, microbial and enzymatic
      biodegradation of plastics and some factors that affect their biodegradability
      are discussed.

PMID- 19865516
TI  - Theoretical investigation of the NO3radical addition to double bonds of limonene.
AB  - The addition reactions of NO(3) to limonene have been investigated using ab
      initio methods. Six different possibilities for NO(3) addition to the double
      bonds, which correspond to the two C-C double bonds (endocyclic or exocyclic)
      have been considered. The negative activation energies for the addition of NO(3)
      to limonene are calculated and the energies of NO(3)-limonene radical adducts are
      found to be 14.55 to 20.17 kcal mol-1 more stable than the separated NO(3) and
      limonene at the CCSD(T)/6-31G(d) + CF level. The results also indicate that the
      endocyclic addition reaction is more energetically favorable than the exocyclic
      one.

PMID- 19865517
TI  - The improvement of hypertension by probiotics: effects on cholesterol, diabetes,
      renin, and phytoestrogens.
AB  - Probiotics are live organisms that are primarily used to improve gastrointestinal
      disorders such as diarrhea, irritable bowel syndrome, constipation, lactose
      intolerance, and to inhibit the excessive proliferation of pathogenic intestinal
      bacteria. However, recent studies have suggested that probiotics could have
      beneficial effects beyond gastrointestinal health, as they were found to improve
      certain metabolic disorders such as hypertension. Hypertension is caused by
      various factors and the predominant causes include an increase in cholesterol
      levels, incidence of diabetes, inconsistent modulation of renin and imbalanced
      sexual hormones. This review discusses the antihypertensive roles of probiotics
      via the improvement and/or treatment of lipid profiles, modulation of insulin
      resistance and sensitivity, the modulation of renin levels and also the
      conversion of bioactive phytoestrogens as an alternative replacement of sexual
      hormones such as estrogen and progesterone.

PMID- 19865518
TI  - The reversal of drug-resistance in tumors using a drug-carrying nanoparticular
      system.
AB  - Medical applications of nanoparticular systems have attracted considerable
      attention because of their potential use in therapeutic targeting of disease
      tissues and their lower level of toxicity against healthy tissue, relative to
      traditional pharmaceutical drugs. The use of nanoparticular systems has been
      shown to overcome the limitations of most anticancer drugs in clinical
      applications. In particular, the improved performance of smarted nanoparticular
      system for solving the drug resistance problems that typically interrupt tumor
      treatment has provided a promising strategy for successful tumor chemotherapy.
      This review highlights recent studies that have examined the therapeutic effect
      of nanoparticular systems on drug-resistant tumors and presents insight on how
      they work.

PMID- 19865519
TI  - Trehalose metabolism: from osmoprotection to signaling.
AB  - Trehalose is a non-reducing disaccharide formed by two glucose molecules. It is
      widely distributed in Nature and has been isolated from certain species of
      bacteria, fungi, invertebrates and plants, which are capable of surviving in a
      dehydrated state for months or years and subsequently being revived after a few
      hours of being in contact with water. This disaccharide has many biotechnological
      applications, as its physicochemical properties allow it to be used to preserve
      foods, enzymes, vaccines, cells etc., in a dehydrated state at room temperature.
      One of the most striking findings a decade ago was the discovery of the genes
      involved in trehalose biosynthesis, present in a great number of organisms that
      do not accumulate trehalose to significant levels. In plants, this disaccharide
      has diverse functions and plays an essential role in various stages of
      development, for example in the formation of the embryo and in flowering.
      Trehalose also appears to be involved in the regulation of carbon metabolism and
      photosynthesis. Recently it has been discovered that this sugar plays an
      important role in plant-microorganism interactions.

PMID- 19865520
TI  - Variations in IC(50) values with purity of mushroom tyrosinase.
AB  - The effects of various inhibitors on crude, commercial and partially purified
      commercial mushroom tyrosinase were examined by comparing IC(50) values. Kojic
      acid, salicylhydroxamic acid, tropolone, methimazole, and ammonium
      tetrathiomolybdate had relatively similar IC(50) values for the crude, commercial
      and partially purified enzyme. 4-Hexylresorcinol seemed to have a somewhat higher
      IC(50) value using crude extracts, compared to commercial or purified tyrosinase.
      Some inhibitors (NaCl, esculetin, biphenol, phloridzin) showed variations in
      IC(50) values between the enzyme samples. In contrast, hydroquinone, lysozyme,
      Zn(2+), and anisaldehyde showed little or no inhibition in concentration ranges
      reported to be effective inhibitors. Organic solvents (DMSO and ethanol) had
      IC(50) values that were similar for some of the tyrosinase samples. Depending of
      the source of tyrosinase and choice of inhibitor, variations in IC(50) values
      were observed.

PMID- 19865521
TI  - Anaerobic biodegradation tests of poly(lactic acid) under mesophilic and
      thermophilic conditions using a new evaluation system for methane fermentation in
      anaerobic sludge.
AB  - Anaerobic biodegradation tests of poly(lactic acid) (PLA) powder were done at the
      thermophilic (55 degrees C) and mesophilic temperature (35 degrees C) under
      aquatic conditions [total solid concentrations of the used sludge were 2.07% (at
      55 degrees C) and 2.24% (at 35 degrees C)] using a newly developed evaluation
      system. With this system, the evolved biogas is collected in a gas sampling bag
      at atmospheric pressure. This method is more convenient than using a pressure
      transducer or inverted graduated cylinder submerged in water. PLA was degraded
      about 60% in 30 days, about 80% in 40 days and about 90% in 60 days at 55 degrees
      C. On the other hand, the PLA degradation started in 55 days at 35 degrees C and
      degradation rate was much slower than at 55 degrees C.

PMID- 19865522
TI  - Reticulate evolution and marine organisms: the final frontier?
AB  - The role that reticulate evolution (i.e., via lateral transfer, viral
      recombination and/or introgressive hybridization) has played in the origin and
      adaptation of individual taxa and even entire clades continues to be tested for
      all domains of life. Though falsified for some groups, the hypothesis of
      divergence in the face of gene flow is becoming accepted as a major facilitator
      of evolutionary change for many microorganisms, plants and animals. Yet, the
      effect of reticulate evolutionary change in certain assemblages has been doubted,
      either due to an actual dearth of genetic exchange among the lineages belonging
      to these clades or because of a lack of appropriate data to test alternative
      hypotheses. Marine organisms represent such an assemblage. In the past half
      century, some evolutionary biologists interested in the origin and trajectory of
      marine organisms, particularly animals, have posited that horizontal transfer,
      introgression and hybrid speciation have been rare. In this review, we provide
      examples of such genetic exchange that have come to light largely as a result of
      analyses of molecular markers. Comparisons among these markers and between these
      loci and morphological characters have provided numerous examples of marine
      microorganisms, plants and animals that possess the signature of mosaic genomes.

PMID- 19865524
TI  - Expression of CD40 and CD40L in gastric cancer tissue and its clinical
      significance.
AB  - To study expression of CD40 and CD40L in gastric cancer tissue we assessed
      gastric cancer patients admitted to the Department of Gastroenterology of The
      First Affiliated Hospital of Soochow University and control subjects. Gastric
      cancer and normal (from around tumours) tissue samples were obtained from
      patients. Venous blood samples (gastric cancer and ulcer groups) were drawn on
      the morning of the day before surgery for the measurement of peripheral sCD40L.
      The expression of CD40 in gastric carcinoma specimens was examined immuno
      histochemically. The clinicopathological factors, including age, sex, tumor size,
      gross appearance, degree of cellular differentiation, histological
      classification, depth of tumor invasion, lymph node metastasis, peritoneal
      dissemination, and TNM stage were analyzed according to the different expression
      of CD40. The results indicated a high CD40 expression in gastric cancer tissues.
      This positive expression of CD40 revealed a significant (P < 0.05) correlation
      with lymphatic metastasis and tumor TNM stage in gastric cancer patients. It is
      concluded that higher CD40 expression existed in expanding type tumors and could
      play an important role in clinical diagnosis of gastric cancer patients.

PMID- 19865525
TI  - A proline-based neuraminidase inhibitor: DFT studies on the zwitterion
      conformation, stability and formation.
AB  - The designs of potent neuraminidase (NA) inhibitors are an efficient way to deal
      with the recent "2009 H1N1" influenza epidemic. In this work, density functional
      calculations were employed to study the conformation, stability and formation of
      the zwitterions of 5-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-4-[(1Z)-1
      propenyl]-(4S,5R)-d-proline (BL), a proline-based NA inhibitor. Compared to
      proline, the zwitterion stability of BL is enhanced by 1.76 kcal mol(-1) due to
      the introduction of functional groups. However, the zwitterion of BL will not
      represent a local minimum on the potential energy surface until the number of
      water molecules increases up to two (n = 2). With the addition of two and three
      water molecules, the energy differences between the zwitterions and corresponding
      canonical isomers were calculated at 3.13 and -1.54 kcal mol(-1), respectively.
      The zwitterions of BL are mainly stabilized by the H-bonds with the water
      molecules, especially in the case of three water molecules where the carboxyl-O
      atoms are largely coordination-saturated by three H-bonds of medium strengths,
      causing the zwitterion stability even superior to the canonical isomer. With the
      presence of two and three water molecules, the energy barriers for the conversion
      processes from the canonical isomers to the zwitterions are equal to 4.96 and
      3.13 kcal mol(-1), respectively. It indicated that the zwitterion formation is
      facile to take place with addition of two molecules and further facilitated by
      more water molecules. Besides, the zwitterion formation of BL is finished in a
      single step, different from other NA inhibitors. Owing to the above advantages,
      BL is a good NA inhibitor candidate and more attention should be paid to
      explorations of BL-based drugs.

PMID- 19865526
TI  - Molecule non-radiative coupling to a metallic nanosphere: an optical theorem
      treatment.
AB  - The non-radiative coupling of a molecule to a metallic spherical particle is
      approximated by a sum involving particle quasistatic polarizabilities. We
      demonstrate that energy transfer from molecule to particle satisfies the optical
      theorem if size effects corrections are properly introduced into the quasistatic
      polarizabilities. We hope that this simplified model gives valuable information
      on the coupling mechanism between molecule and metallic nanostructures available
      for, e.g., surface enhanced spectroscopy signal analysis.

PMID- 19865523
TI  - Molecular toxicology of substances released from resin-based dental restorative
      materials.
AB  - Resin-based dental restorative materials are extensively used today in dentistry.
      However, significant concerns still remain regarding their biocompatibility. For
      this reason, significant scientific effort has been focused on the determination
      of the molecular toxicology of substances released by these biomaterials, using
      several tools for risk assessment, including exposure assessment, hazard
      identification and dose-response analysis. These studies have shown that
      substances released by these materials can cause significant cytotoxic and
      genotoxic effects, leading to irreversible disturbance of basic cellular
      functions. The aim of this article is to review current knowledge related to
      dental composites' molecular toxicology and to give implications for possible
      improvements concerning their biocompatibility.

PMID- 19865527
TI  - Sage tea drinking improves lipid profile and antioxidant defences in humans.
AB  - Salvia officinalis (common sage) is a plant with antidiabetic properties. A pilot
      trial (non-randomized crossover trial) with six healthy female volunteers (aged
      40-50) was designed to evaluate the beneficial properties of sage tea consumption
      on blood glucose regulation, lipid profile and transaminase activity in humans.
      Effects of sage consumption on erythrocytes' SOD and CAT activities and on Hsp70
      expression in lymphocytes were also evaluated. Four weeks sage tea treatment had
      no effects on plasma glucose. An improvement in lipid profile was observed with
      lower plasma LDL cholesterol and total cholesterol levels as well as higher
      plasma HDL cholesterol levels during and two weeks after treatment. Sage tea also
      increased lymphocyte Hsp70 expression and erythrocyte SOD and CAT activities. No
      hepatotoxic effects or other adverse effects were observed.

PMID- 19865529
TI  - The influence of disorder on thermotropic nematic liquid crystals phase behavior.
AB  - We review the theoretical research on the influence of disorder on structure and
      phase behavior of condensed matter system exhibiting continuous symmetry breaking
      focusing on liquid crystal phase transitions. We discuss the main properties of
      liquid crystals as adequate systems in which several open questions with respect
      to the impact of disorder on universal phase and structural behavior could be
      explored. Main advantages of liquid crystalline materials and different
      experimental realizations of random field-type disorder imposed on liquid crystal
      phases are described.

PMID- 19865528
TI  - Host defense peptides as effector molecules of the innate immune response: a
      sledgehammer for drug resistance?
AB  - Host defense peptides can modulate the innate immune response and boost infection
      resolving immunity, while dampening potentially harmful pro-inflammatory (septic)
      responses. Both antimicrobial and/or immunomodulatory activities are an integral
      part of the process of innate immunity, which itself has many of the hallmarks of
      successful anti-infective therapies, namely rapid action and broad-spectrum
      antimicrobial activities. This gives these peptides the potential to become an
      entirely new therapeutic approach against bacterial infections. This review
      details the role and activities of these peptides, and examines their
      applicability as development candidates for use against bacterial infections.

PMID- 19865530
TI  - Experimental and computational characterization of biological liquid crystals: a
      review of single-molecule bioassays.
AB  - Quantitative understanding of the mechanical behavior of biological liquid
      crystals such as proteins is essential for gaining insight into their biological
      functions, since some proteins perform notable mechanical functions. Recently,
      single-molecule experiments have allowed not only the quantitative
      characterization of the mechanical behavior of proteins such as protein unfolding
      mechanics, but also the exploration of the free energy landscape for protein
      folding. In this work, we have reviewed the current state-of-art in single
      molecule bioassays that enable quantitative studies on protein unfolding
      mechanics and/or various molecular interactions. Specifically, single-molecule
      pulling experiments based on atomic force microscopy (AFM) have been overviewed.
      In addition, the computational simulations on single-molecule pulling experiments
      have been reviewed. We have also reviewed the AFM cantilever-based bioassay that
      provides insight into various molecular interactions. Our review highlights the
      AFM-based single-molecule bioassay for quantitative characterization of
      biological liquid crystals such as proteins.

PMID- 19865531
TI  - Degradability of polymers for implantable biomedical devices.
AB  - Many key components of implantable medical devices are made from polymeric
      materials. The functions of these materials include structural support,
      electrical insulation, protection of other materials from the environment of the
      body, and biocompatibility, as well as other things such as delivery of a
      therapeutic drug. In such roles, the stability and integrity of the polymer, over
      what can be a very long period of time, is very important. For most of these
      functions, stability over time is desired, but in other cases, the opposite-the
      degradation and disappearance of the polymer over time is required. In either
      case, it is important to understand both the chemistry that can lead to the
      degradation of polymers as well as the kinetics that controls these reactions.
      Hydrolysis and oxidation are the two classes of reactions that lead to the
      breaking down of polymers. Both are discussed in detail in the context of the
      environmental factors that impact the utility of various polymers for medical
      device applications. Understanding the chemistry and kinetics allows prediction
      of stability as well as explanations for observations such as porosity and the
      unexpected behavior of polymeric composite materials in some situations. In the
      last part, physical degradation such interfacial delamination in composites is
      discussed.

PMID- 19865533
TI  - Eu-doped BaTiO3powder and film from sol-gel process with polyvinylpyrrolidone
      additive.
AB  - Transparent BaTiO(3):Eu(3+) films were prepared via a sol-gel method and dip
      coating technique, using barium acetate, titanium butoxide, and
      polyvinylpyrrolidone (PVP) as modifier viscosity. BaTiO(3):Eu(3+) films ~500 nm
      thick, crystallized after thermal treatment at 700 masculineC. The powders
      revealed spherical and rod shape morphology. The optical quality of films showed
      a predominant band at 615 nm under 250 nm excitation. A preliminary luminescent
      test provided the properties of the Eu(3+) doped BaTiO(3).

PMID- 19865534
TI  - Liquid crystals in tribology.
AB  - Two decades ago, the literature dealing with the possible applications of low
      molar mass liquid crystals, also called monomer liquid crystals (MLCs), only
      included about 50 references. Today, thousands of papers, conference reports,
      books or book chapters and patents refer to the study and applications of MLCs as
      lubricants and lubricant additives and efforts are made to develop new commercial
      applications. The development of more efficient lubricants is of paramount
      technological and economic relevance as it is estimated that half the energy
      consumption is dissipated as friction. MLCs have shown their ability to form
      ordered boundary layers with good load-carrying capacity and to lower the
      friction coefficients, wear rates and contact temperature of sliding surfaces,
      thus contributing to increase the components service life and to save energy.
      This review includes the use of MLCs in lubrication, and dispersions of MLCs in
      conventional polymers (PDMLCs). Finally, new lubricating system composed of MLC
      blends with surfactants, ionic liquids or nanophases are considered.

PMID- 19865532
TI  - Mechanisms regulating skin pigmentation: the rise and fall of complexion
      coloration.
AB  - Skin pigmentary abnormalities are seen as aesthetically unfavorable and have led
      to the development of cosmetic and therapeutic treatment modalities of varying
      efficacy. Hence, several putative depigmenting agents aimed at modulating skin
      pigmentation are currently being researched or sold in commercially available
      products. In this review we will discuss the regulation of processes that control
      skin complexion coloration. This includes direct inhibition of tyrosinase and
      related melanogenic enzymes, regulation of melanocyte homeostasis, alteration of
      constitutive and facultative pigmentation and down-regulation of melanosome
      transfer to the keratinocytes. These various processes, in the complex mechanism
      of skin pigmentation, can be regulated individually or concomitantly to alter
      complexion coloration and thus ameliorate skin complexion diseases.

PMID- 19865535
TI  - Chromosomal location of traits associated with wheat seedling water and
      phosphorus use efficiency under different water and phosphorus stresses.
AB  - The objective of this study was to locate chromosomes for improving water and
      phosphorus-deficiency tolerance of wheat at the seedling stage. A set of Chinese
      Spring-Egyptian Red wheat substitution lines and their parent Chinese Spring
      (recipient) and Egyptian Red (donor) cultivars were measured to determine the
      chromosomal locations of genes controlling water use efficiency (WUE) and
      phosphorus use efficiency (PUE) under different water and phosphorus conditions.
      The results underlined that chromosomes 1A, 7A, 7B, and 3A showed higher leaf
      water use efficiency (WUE(l) = Pn/Tr; Pn = photosynthetic rate; Tr =
      transpiration rate) under W-P (Hoagland solution with 1/2P), -W-P (Hoagland
      solution with 1/2P and 10% PEG). Chromosomes 7A, 3D, 2B, 3B, and 4B may carry
      genes for positive effects on individual plant water use efficiency (WUE(p) =
      biomass/TWC; TWC = total water consumption) under WP (Hoagland solution), W-P and
      -W-P treatment. Chromosomes 7A and 7D carry genes for PUE enhancement under WP, 
      WP (Hoagland solution with 10% PEG) and W-P treatment. Chromosome 7A possibly has
      genes for controlling WUE and PUE simultaneously, which indicates that WUE and
      PUE may share the same genetic background. Phenotypic and genetic analysis of the
      investigated traits showed that photosynthetic rate (Pn) and transpiration rate
      (Tr), Tr and WUE(l) showed significant positive and negative correlations under
      WP, W-P, -WP and -W-P, W-P, -WP treatments, respectively. Dry mass (DM), WUE(P),
      PUT (phosphorus uptake) all showed significant positive correlation under WP, W-P
      and -WP treatment. PUE and phosphorus uptake (PUT = P uptake per plant) showed
      significant negative correlation under the four treatments. The results might
      provide useful information for improving WUE and PUE in wheat genetics.

PMID- 19865536
TI  - Binding and docking interactions of NO, CO and O2in heme proteins as probed by
      density functional theory.
AB  - Dynamics and reactivity in heme proteins include direct and indirect interactions
      of the ligands/substrates like CO, NO and O(2) with the environment. Direct
      electrostatic interactions result from amino acid side chains in the inner
      cavities and/or metal coordination in the active site, whereas indirect
      interactions result by ligands in the same coordination sphere. Interactions play
      a crucial role in stabilizing transition states in catalysis or altering ligation
      chemistry. We have probed, by Density Functional Theory (DFT), the perturbation
      degree in the stretching vibrational frequencies of CO, NO and O(2) molecules in
      the presence of electrostatic interactions or hydrogen bonds, under conditions
      simulating the inner cavities. Moreover, we have studied the vibrational
      characteristics of the heme bound form of the CO and NO ligands by altering the
      chemistry of the proximal to the heme ligand. CO, NO and O(2) molecules are
      highly polarizable exerting vibrational shifts up to 80, 200 and 120 cm(-1),
      respectively, compared to the non-interacting ligand. The importance of Density
      Functional Theory (DFT) methodology in the investigation of the heme-ligand
      protein interactions is also addressed.

PMID- 19865537
TI  - Lysis of Microcystis aeruginosa with extracts from Chinese medicinal herbs.
AB  - Boiling water extracts of 66 selected Chinese medicinal herbs were screened for
      their anticyanobaterial activity against Microcystis aeruginosa by the soft-agar
      overlayer (SAO) method. Results indicated that extracts from 16 materials could
      inhibit the growth of this bacterial species. Among these anticyanobacterial
      samples, eight extracts showed low minimum inhibitory concentrations (MIC),
      including four extracts with MICs between 1 and 6 mg/mL, and four extracts with
      MICs < 1 mg/mL which could be considered useful to prevent the outbreak of
      cyanobacteria before the appearance of cyanobacterial blooms. Further study
      showed that three extracts with MIC values < 1 mg/mL induced intensive
      chlorophyll-a lysis within 7 days at the MIC. The results suggested that highly
      efficient anticyanobacterial compounds must be involved in the inhibitory
      activities. The final results indicated these three extracts (from Malaphis
      chinensis, Cynips gallae-tinctoriae and Fructus mume) had the potential to be
      developed as algicides due to their remarkably anticyanobacterial activities.

PMID- 19865538
TI  - Effect of quercetin on paraoxonase 2 levels in RAW264.7 macrophages and in human
      monocytes--role of quercetin metabolism.
AB  - There is increasing evidence that the intracellular antioxidant enzyme
      paraoxonase 2 (PON2) may have a protective function in the prevention of
      atherogenesis. An enhancement of PON2 activity by dietary factors including
      flavonoids is therefore of interest. In the present study we determined the
      effect of quercetin on paraoxonase 2 levels in cultured murine macrophages in
      vitro and in overweight subjects with a high cardiovascular risk phenotype
      supplemented with 150 mg quercetin/day for 42 days in vivo. Supplementation of
      murine RAW264.7 macrophages in culture with increasing concentrations of
      quercetin (1, 10, 20 micromol/L) resulted in a significant increase in PON2 mRNA
      and protein levels, as compared to untreated controls. Unlike quercetin, its
      glucuronidated metabolite quercetin-3-glucuronide did not affect PON2 gene
      expression in cultured macrophages. However the methylated quercetin derivative
      isorhamnetin enhanced PON2 gene expression in RAW264.7 cells to similar extent
      like quercetin. Although supplementing human volunteers with quercetin was
      accompanied by a significant increase in plasma quercetin concentration, dietary
      quercetin supplementation did not change PON2 mRNA levels in human monocytes in
      vivo. Current data indicate that quercetin supplementation increases PON2 levels
      in cultured monocytes in vitro but not in human volunteers in vivo.

PMID- 19865539
TI  - Implementation of a reuse process for liquid crystal displays using an eccentric
      form tool.
AB  - This study presents a new nanotechnology application involving an ITO thin-film
      removal reuse process using an eccentric-form negative electrode, offering a fast
      removal rate from the surface of liquid crystal displays (LCDs). For the
      precision removal process, a small amount of eccentricity of the negative
      electrode or a higher rotational speed of the negative electrode corresponds to a
      higher etching rate for the ITO. A higher flow velocity of the electrolyte and a
      higher working temperature also correspond to a higher removal rate. The average
      effect of the eccentricity is better than the effects of a pulsed current, while
      the current rating need not be prolonged by the off-time.

PMID- 19865540
TI  - Functional analysis of familial Asp67Glu and Thr1051Ser BRCA1 mutations in
      breast/ovarian carcinogenesis.
AB  - Estrogen is believed to be pre-initiator in the risk of breast cancer. The BRCA1
      is a tumor suppressor gene associated with breast and ovarian cancer risk. This
      report describes functional analysis of two BRCA1 missense mutations (Asp67Glu
      and Thr1051Ser) observed in the familial breast/ovarian cancer patients in
      Thailand. Levels of luciferase activity of the two mutations were relatively
      lower than in the wild-type BRCA1. It is indicated that mutants may fail to
      promote the estrogen receptor dependent functions. It is presumed that estrogen
      and insulin/IGF-1 regulate c-Myc and cyclin D1 during breast cancer cell
      proliferation. It is also likely to affect ubiquitination mechanism. Since three
      affected cancer families carry the Asp67Glu mutation, it is believed that this
      type of mutation could have some effect on breast/ovarian cancer progression.

PMID- 19865541
TI  - A surgical review of the priority claims attributed to Abraham Groves (1847
      1935).
AB  - BACKGROUND: The practice of surgery had changed little over millennia when
      Abraham Groves and William Osler attended medical school together in Toronto,
      Ontario. The invention of anesthesia sparked such rapid development that by the
      time of Groves' and Osler's deaths, surgical practice resembled the current
      model. Several priority claims have been attributed to Groves' life in surgery,
      including aseptic surgery (1874), suprapubic lithotomy (1878), appendectomy
      (1883), surgical gloves (1885) and cancer radiotherapy (1903). These claims arise
      from an autobiography written by Groves at the age of 87 years in 1934. METHODS:
      The purpose of this paper is to assess these priority claims from a modern
      surgical perspective. We did a systematic search of contemporary (1873-1934) and
      modern journals for articles by or about Groves. We searched relevant archives
      and museums. We reviewed the 1934 autobiography, notes held by descendants,
      reminiscences by contemporaries and collateral information. We assessed the
      information not only for priority but also for the development of organized
      surgical thought. RESULTS: Groves published frequently throughout his career;
      thus far we have located 36 papers, almost all of which were published in
      Canadian journals. He spoke regularly at regional meetings in Ontario. Many
      medical students apprenticed with him (including his brother, son and grandson),
      he established a hospital and he founded a school of nursing. His contemporaries
      published complimentary reminiscences, but no correspondence with his classmate,
      William Osler, is known. Groves' priority claims for aseptic surgery, suprapubic
      lithotomy and radiotherapy are supported by contemporary publications. Groves
      independently developed an organized surgical system that remains valid today.
      Priority claims for appendectomy and the use of surgical gloves are entirely
      consistent with that system. CONCLUSION: Although Groves' impact was reduced by
      his location and the limited circulation of the journals in which he wrote, he
      demonstrated a systematic understanding of modern surgery well ahead of his
      contemporaries.

PMID- 19865542
TI  - A retrospective review of general surgery training outcomes at the University of
      Toronto.
AB  - BACKGROUND: Surgical educators have struggled with achieving an optimal balance
      between the service workload and education of surgical residents. In Ontario, a
      variety of factors during the past 12 years have had the net impact of reducing
      the clinical training experience of general surgery residents. We questioned what
      impact the reductions in trainee workload have had on general surgery graduates
      at the University of Toronto. METHODS: We evaluated graduates from the University
      of Toronto general surgery training program from 1995 to 2006. We compared final
      year In-Training Evaluation Reports (ITERs) of trainees during this interval. For
      purposes of comparison, we subdivided residents into 4 groups according to year
      of graduation (1995-1997, 1998-2000, 2001-2003 and 2004-2006). We evaluated
      postgraduate "performance" by categorizing residents into 1 of 4 groups: first,
      residents who entered directly into general surgery practice after graduation;
      second, residents who entered into a certification subspecialty program of the
      Royal College of Physicians and Surgeons of Canada (RCPSC); third, residents who
      entered into a noncertification program of the RCPSC; and fourth, residents who
      entered into a variety of nonregulated "clinical fellowships." RESULTS: We
      assessed and evaluated 118 of 134 surgical trainees (88%) in this study. We
      included in the study graduates for whom completed ITER records were available
      and postgraduate training records were known and validated. The mean scores for
      each of the 5 evaluated residency training parameters included in the ITER
      (technical skills, professional attitudes, application of knowledge, teaching
      performance and overall performance) were not statistically different for each of
      the 4 graduating groups from 1995 to 2006. However, we determined that there were
      statistically fewer general surgery graduates (p < 0.05) who entered directly
      into general surgery practice in the 2004-2006 group compared with the 1998-2000
      and 2001-2003 groups. The graduates from 2004 to 2006 who did not enter into
      general surgery practice appeared to choose a clinical fellowship. CONCLUSION:
      These observations may indicate that recent surgical graduates possess an
      acceptable skill set but may lack the clinical confidence and experience to enter
      directly into general surgery practice. Evidence seems to indicate that the
      clinical fellowship has become an unregulated surrogate extension of the training
      program whereby surgeons can gain additional clinical experience and surgical
      expertise.

PMID- 19865543
TI  - Development of the Veritas plot and its application in cardiac surgery: an
      evidence-synthesis graphic tool for the clinician to assess multiple meta
      analyses reporting on a common outcome.
AB  - BACKGROUND: Meta-analyses may be prone to generating misleading results because
      of a paucity of experimental studies (especially in surgery); publication bias;
      and heterogeneity in study design, intervention and the patient population of
      included studies. When investigating a specific clinical or scientific question
      on which several relevant meta-analyses may have been published, value judgments
      must be applied to determine which analysis represents the most robust evidence.
      These value judgments should be specifically acknowledged. We designed the
      Veritas plot to explicitly explore important elements of quality and to
      facilitate decision-making by highlighting specific areas in which meta-analyses
      are found to be deficient. Furthermore, as a graphic tool, it may be more
      intuitive than when similar data are presented in a tabular or text format.
      METHODS: The Veritas plot is an adaption of the radar plot, a graphic tool for
      the description of multiattribute data. Key elements of meta-analytical quality
      such as heterogeneity, publication bias and study design are assessed. Existing
      qualitative methods such as the Assessment of Multiple Systematic Reviews
      (AMSTAR) tool have been incorporated in addition to important considerations when
      interpreting surgical meta-analyses such as the year of publication and
      population characteristics. To demonstrate the potential of the Veritas plot to
      inform clinical practice, we apply the Veritas plot to the meta-analytical
      literature comparing the incidence of 30-day stroke in off-pump coronary artery
      bypass surgery and conventional coronary artery bypass surgery. RESULTS: We
      demonstrate that a visually-stimulating and practical evidence-synthesis tool can
      direct the clinician and scientist to a particular meta-analytical study to
      inform clinical practice. The Veritas plot is also cumulative and allowed us to
      assess the quality of evidence over time. CONCLUSION: We have presented a
      practical graphic application for scientists and clinicians to identify and
      interpret variability in meta-analyses. Although further validation of the
      Veritas plot is required, it may have the potential to contribute to the
      implementation of evidence-based practice.

PMID- 19865544
TI  - Injury in Kampala, Uganda: 6 years later.
AB  - BACKGROUND: Trauma remains a tremendous cause of morbidity and mortality in most
      countries. The objective of our study was to describe injury from trauma at the
      major referral hospital in Uganda over a 1-year period. METHODS: Trauma registry
      forms have been completed for all trauma patients seen between August 2004 and
      July 2005 at the casualty department of Mulago Hospital in Kampala, Uganda. We
      also obtained 2-week follow-up data, and we compared these data with 1998 data
      from the same institution. RESULTS: In all, 3778 patients were entered into the
      database, with complete data available for 93.5% of patients. Patients had a mean
      age of 26 (standard deviation [SD] 12) years, and 75% of patients were male. The
      mean Kampala Trauma Score (KTS) was 9.1 (SD 1). We classified injuries as mild
      (82%; KTS 9-10), moderate (14%; KTS 7-8) and severe (4%; KTS <or= 6). On arrival,
      57% of patients were treated and sent home, 41.6% were admitted and 0.4% died in
      the casualty department. At 2-week follow-up, 85% were discharged, 12% were still
      in hospital and 2.7% had died. Causes of injury included road traffic collisions
      (50%), blunt force (15%), falls (10%), stab wounds (9%), animal bites (7%), burns
      (6%) and gunshot wounds (1%). Causes of mortality were road traffic collisions
      (61%), burns (15%), blunt trauma (8.6%), falls (6.5%), stabs/cuts (5.4%) and
      other (3.3%). Data from 1998 demonstrated a similar spectrum of injuries but with
      a mortality of 7.2%. CONCLUSION: Road traffic collisions are the greatest cause
      of morbidity and mortality from injury in Kampala, Uganda. When comparing data
      from 1998 and 2005, the spectrum of injury remained similar, but mortality
      decreased from 7.2% to 2.7%.

PMID- 19865545
TI  - Weather and chinook winds in relation to spontaneous pneumothoraces.
AB  - BACKGROUND: Spontaneous pneumothorax (SP) results from the rupture of blebs or
      emphysematous bullae. Rapid changes in weather may precipitate this process. The
      city of Calgary is well suited to examine the effects of weather and specifically
      the rapid changes in weather associated with a chinook event and the occurrence
      of SP. METHODS: We performed a retrospective chart review of all cases of SP in
      the Calgary Health Region from 2001 to 2005. We obtained local hourly weather
      data over the same period from Environment Canada. We then compared the rates of
      SP on chinook and nonchinook days. Further, we compared mean daily temperature,
      humidity, wind speed and atmospheric pressure on chinook and nonchinook days.
      RESULTS: In all, 220 SP events from 149 patients occurred during the 4.5-year
      study period. There was no significant difference in the rate of SP on chinook
      days versus nonchinook days (p = 0.80). Similarly, there was no significant
      difference in the rate of SP in each of the 4 seasons (p = 0.30). We observed
      significantly higher average wind speed and lower mean atmospheric pressure on
      days with SP versus days without (p = 0.009, p = 0.020, respectively). There was
      no difference in mean temperature or mean relative humidity when comparing days
      with SP versus days without. CONCLUSION: We found no association between SP and
      chinook events. We observed significantly higher wind speeds and lower
      atmospheric pressures on days with SP versus days without.

PMID- 19865546
TI  - Canadian experience with percutaneous endovascular aneurysm repair: short-term
      outcomes.
AB  - BACKGROUND: To decrease the morbidity associated with cut-downs during
      endovascular aneurysm repair, some authors have suggested the totally
      percutaneous endovascular repair (PEVAR). The goal of this report is to evaluate
      and describe our centre's experience with the total percutaneous endovascular
      aneurysm repair (PEVAR) for aortic abdominal aneurysm (AAA). METHODS: We
      performed a retrospective analysis of 15 consecutive patients with AAA, including
      1 with right common iliac artery aneurysm. RESULTS: There were 12 men and 3 women
      with a mean age of 74 (standard deviation [SD] 2) years who underwent PEVAR with
      a Perclose ProGlide suture-mediated closure system between July 2007 and July
      2008. All surgeries were elective. Forty percent of patients had a history of
      smoking, 73% were hypertensive, 33% were diabetic, 20% had chronic obstructive
      pulmonary disease and 40% had coronary artery disease. Fourteen patients had
      bilateral deployment for bifurcated devices (7 bifurcated Gore Excluder, 7
      bifurcated Cook Zenith grafts), and 1 patient had unilateral deployment for a
      Cook Zenith device. The outer diameter of the sheaths used for puncture sites was
      on average 18.1-Fr (SD 0.6), with main bodies being 21.1-Fr (SD 0.3) and
      contralateral sides 15-Fr (SD 0.3). Procedural success was 93%, with 1 patient
      requiring a femoral artery cut-down because of failure of the Perclose device to
      deploy in the groin. Another patient had persistent venous bleeding in 1 puncture
      site that stopped with skin suturing. Endovascular aneurysm repair was 100% with
      no conversion to open surgery and no type-I endoleaks. The mean length of stay in
      hospital was 2.2 (SD 0.4) days. There were no long-term groin complications at 6
      (SD 1) months' follow-up. CONCLUSION: To our knowledge, this is the first
      Canadian report of experience with PEVAR using the Perclose device. The technique
      is safe, reliable and allows discharge of patients soon after surgery.

PMID- 19865547
TI  - Efficacy of different fixation devices in maintaining an initial reduction for
      surgically managed distal radius fractures.
AB  - BACKGROUND: Fracture of the distal radius is a common injury. Many treatment
      options exist for the surgical management of extra-articular and intra-articular
      distal radius fractures. The best method of treatment for these fractures remains
      controversial. We sought to examine radiographic outcomes of patients treated
      with non-spanning external fixator (NSEF), open reduction and internal fixation
      (ORIF) with locking plates and screws or closed reduction and percutaneous
      pinning (CRPP) and compare their ability to maintain radiographic parameters over
      the initial 6-week postoperative period. METHODS: We performed a retrospective
      review of radiographs showing 211 distal radius fractures treated with NSEF, ORIF
      or CRPP. We examined the images for a variety of radiological parameters.
      Measurements were taken immediately postoperatively and at 6-week follow-up to
      determine whether there was any loss of reduction. RESULTS: Of the 211 fractures,
      104 (49.3%) were type-A fractures, 12 (5.7%) were type-B fractures and 95 (45.0%)
      were type-C fractures. The 3 treatments maintained the reduction obtained at
      surgery until healing. The CRPP and ORIF treatments failed to maintain correction
      in ulnar variance for the 6-week period; however, only ORIF actually changed the
      ulnar variance from presurgical values. CONCLUSION: Treatment with ORIF for
      comminuted, intra-articular distal radius fractures produces good radiographic
      results with maintenance of surgical radiographic parameters, whereas NSEFand
      CRPP of less complex fractures also provide good results. This suggests that
      fracture-specific fixation with CRPP or NSEF are sufficient for certain distal
      radius fractures.

PMID- 19865548
TI  - Microscopic colitis: a review for the surgical endoscopist.
AB  - Microscopic colitis (MC) is an inflammatory condition of the colon distinct from
      Crohn disease or ulcerative colitis that can cause chronic diarrhea as well as
      cramping and bloating. Although it was first described 30 years ago, awareness of
      this entity as a cause of diarrhea has only become more widespread recently. Up
      to 20% of adults with chronic diarrhea who have an endoscopically normal
      colonoscopy may have MC. Endoscopic and radiological examinations are usually
      normal, but histology reveals increased lymphocytes in the colonic mucosa, which
      typically cause watery nonbloody diarrhea. Treatment is initially supportive but
      can include corticosteroids and immunomodulatory therapy for resistant cases.
      Since surgeons perform a large number of colonoscopies and sigmoidoscopies to
      assess diarrhea, it is important to be aware of this disease and to look for it
      with mucosal biopsy in appropriate patients.

PMID- 19865549
TI  - The occult pneumothorax: what have we learned?
AB  - Supine anteroposterior chest radiography is an insensitive test for posttraumatic
      pneumothoraces. Computed tomography often detects pneumothoraces that were not
      diagnosed on chest radiography (occult pneumothoraces). Whereas the incidence of
      occult pneumothoraces approximates 5% of all trauma registry patients, this value
      approaches 15% among injured patients undergoing computed tomography. Up to 76%
      of all pneumothoraces may be occult to supine chest radiography with real-time
      interpretation by trauma teams. Although the size and intrathoracic distribution
      (anterior) of overt and occult pneumothoraces are similar, significantly more
      patients with occult pneumothoraces undergo tube thoracostomy compared with those
      with overt pneumothoraces. This pattern extends both to patients receiving
      mechanical ventilation and those with penetrating trauma. As an early clinical
      predictor available during the resuscitation of a trauma patient, only
      subcutaneous emphysema is predictive of a concurrent occult pneumothorax. The
      majority of patients with occult pneumothoraces (85%) do not have subcutaneous
      emphysema, however. Thoracic ultrasonography, as part of a bedside extended
      focused assessment with sonography for trauma examination, detects 92%-100% of
      all pneumothoraces and represents a simple extension of the clinician's physical
      examination. The final remaining question is whether clinicians can safely omit
      tube thoracostomy in some patients with occult pneumothoraces concurrent to
      positive pressure ventilation. This omission would avoid subjecting patients to
      the 22% risk of major chest tube-related insertional, positional and infective
      complications.

PMID- 19865550
TI  - Musculoskeletal case 45.

PMID- 19865551
TI  - Aortic thrombosis complicating Crohn disease: an unusual complication.

PMID- 19865552
TI  - Massive gastrointestinal bleeding caused by stromal tumour of the jejunum.

PMID- 19865553
TI  - Laparoscopic treatment of primary hyperaldosteronism in a pregnant patient.

PMID- 19865554
TI  - Intussuscepted intestine through a rectal foreign body.

PMID- 19865555
TI  - Pseudomonas aeruginosa-infected infrarenal abdominal aorta pseudoaneurysm
      secondary to laparoscopic colorectal surgery: failure of endovascular stent graft
      treatment after primary open repair failed.

PMID- 19865556
TI  - Left colon and liver hemangiomas.

PMID- 19865557
TI  - Complete anemia reversal after surgical excision of mesenteric hyaline-vascular
      unicentric Castleman disease.

PMID- 19865558
TI  - Management of a small incidentally discovered retroperitoneal synovial sarcoma.

PMID- 19865559
TI  - Minimally invasive excision of a mediastinal cystic lymphangioma.

PMID- 19865560
TI  - Control of the bleeding gallbladder bed using a pedicled falciform ligament flap
      based on the left inferior phrenic artery and middle segment hepatic artery.

PMID- 19865561
TI  - Mock appendicitis: small bowel perforation secondary to lung cancer metastasis.

PMID- 19865562
TI  - Traumatic abdominal hernia with presternal herniation.

PMID- 19865563
TI  - Splenic hydatid cyst.

PMID- 19865564
TI  - Minimal abdominal adhesions after Sepramesh repair of a parastomal hernia.

PMID- 19865565
TI  - Isolated metastasis to the cerebellopontine angle secondary to breast cancer.

PMID- 19865566
TI  - Esophageal carcinoma presented with a skull tumour.

PMID- 19865569
TI  - Does general surgery residency training provide competence in community-based
      pediatric surgery?

PMID- 19865567
TI  - Isolated quadrilateral plate fracture: an unusual acetabular fracture.

PMID- 19865570
TI  - H1N1 and the surgeon.

PMID- 19865571
TI  - Getting started with robotics in general surgery with cholecystectomy: the
      Canadian experience.
AB  - BACKGROUND: The value of robotics in general surgery may be for advanced
      minimally invasive procedures. Unlike other specialties, formal fellowship
      training opportunities for robotic general surgery are few. As a result, most
      surgeons currently develop robotic skills in practice. Our goal was to determine
      whether robotic cholecystectomy is a safe and effective bridge to advanced
      robotics in general surgery. METHODS: Before performing advanced robotic
      procedures, 2 surgeons completed the Intuitive Surgical da Vinci training course
      and agreed to work together on all procedures. Clinical surgery began with da
      Vinci cholecystectomy with a plan to begin advanced procedures after at least 10
      cholecystectomies. We performed a retrospective review of our pilot series of
      robotic cholecystectomies and compared them with contemporaneous laparoscopic
      controls. The primary outcome was safety, and the secondary outcome was learning
      curve. RESULTS: There were 16 procedures in the robotics arm and 20 in the
      laparoscopic arm. Two complications (da Vinci port-site hernia, transient
      elevation of liver enzymes) occurred in the robotic arm, whereas only 1
      laparoscopic patient (slow to awaken from anesthetic) experienced a complication.
      None was significant. The mean time required to perform robotic cholecystectomy
      was significantly longer than laparoscopic surgery (91 v. 41 min, p < 0.001). The
      mean time to clear the operating room was significantly longer for robotic
      procedures (14 v. 11 min, p = 0.015). We observed a trend showing longer mean
      anesthesia time for robotic procedures (23 v. 15 min). Regarding learning curve,
      the mean operative time needed for the first 3 robotic procedures was longer than
      for the last 3 (101 v. 80 min); however, this difference was not significant.
      Since this experience, the team has confidently gone on to perform robotic
      biliary, pancreatic, gastresophageal, intestinal and colorectal operations.
      CONCLUSION: Robotic cholecystectomy can be performed reliably; however, owing to
      the significant increase in operating room resources, it cannot be justified for
      routine use. Our experience, however, demonstrates that robotic cholecystectomy
      is one means by which general surgeons may gain confidence in performing advanced
      robotic procedures.

PMID- 19865572
TI  - Computer-assisted FluoroGuide navigation of unicompartmental knee arthroplasty.
AB  - BACKGROUND: Most authorities recognize minimally invasive unicompartmental knee
      arthroplasty (UKA) as technically demanding with concerns regarding loss of
      implantation accuracy. We have previously reported on the potential inaccuracy of
      femoral intramedullary guides in UKA leading to poor component positioning. Our 3
      dimensional analysis of alignment error showed that a short, narrow
      intramedullary rod inserted according to the manufacturer's specifications did
      not accurately find the direction of the anatomic axis, with errors occurring in
      both the coronal and sagittal planes. We sought to evaluate whether a
      fluoroscopic computer-assisted minimally invasive UKA procedure would improve the
      accuracy and precision in the placement of the femoral component in the coronal
      and sagittal planes compared with conventional surgery. METHODS: We performed a
      prospective study involving cohorts of 45 conventional versus 53 navigated UKAs.
      A single surgeon performed all surgeries over a 4-year period. RESULTS: Pain and
      knee function significantly improved in both surgical groups at 1 and 2 years
      after surgery. At a minimum of 1-year follow-up, radiographic evaluation revealed
      significant improvements in coronal alignment precision of the tibial component
      (p = 0.026) and sagittal alignment precision of the femoral component for the
      navigated group (p = 0.037). The use of a fluoroscopic computer-assisted
      technique did not significantly improve the accuracy of any of the alignment
      angles. CONCLUSION: We cannot justify the additional expense and complexity
      imposed by fluoroscopic navigation despite the observed improvements in alignment
      precision. Improved positioning precision may translate into a greater number of
      long-term functional results, but larger, longer-term studies are needed.

PMID- 19865573
TI  - Do corticosteroids reduce the risk of fat embolism syndrome in patients with long
      bone fractures? A meta-analysis.
AB  - BACKGROUND: Fat embolism syndrome (FES) is a potentially lethal condition most
      commonly seen in polytrauma patients with multiple long-bone fractures. Treatment
      has centred around supportive care and early fracture fixation. Several small
      clinical trials have suggested corticosteroids benefit patients with FES, but
      this treatment remains controversial. Our objective was to determine the effect
      of corticosteroids in preventing FES in patients with long-bone fractures.
      METHODS: We conducted a meta-analysis of published studies of patients with long
      bone fractures who were randomly assigned to groups receiving corticosteroids or
      standard treatment for the prevention of FES (1966-2006). Data were extracted on
      quality, population, intervention and outcomes. Our primary outcome was the
      development of FES. We used random-effects models to pool results across studies,
      assessing for study heterogeneity. RESULTS: Of the 104 studies identified, 7 met
      our eligibility criteria. Overall, the quality of the trials was poor. Our pooled
      analysis of 389 patients found that corticosteroids reduced the risk of FES by
      78% (95% confidence interval [CI] 43%-92%) and that only 8 patients needed to be
      treated (95% CI 5-13 patients) to prevent 1 case of FES. Similarly,
      corticosteroids significantly reduced the risk of hypoxia. We found no
      differences in the rates of mortality or infection. Rates of avascular necrosis
      were not reported in any of these studies. CONCLUSION: Evidence suggests that
      corticosteroids may be beneficial in preventing FES and hypoxia but not mortality
      in patients with long-bone fractures. The risk of infection is not increased with
      the use of corticosteroids. However, methodological limitations of these trials
      necessitate a large confirmatory randomized trial.

PMID- 19865574
TI  - Recent evolution in demographic and clinical characteristics and in-hospital
      morbidity in patients undergoing coronary surgery.
AB  - BACKGROUND: Over the last 12 years, the demographic and clinical characteristics
      of patients undergoing myocardial revascularization surgery have evolved rapidly.
      The goal of our study was to analyze the evolution of these trends and the
      results of these surgical interventions. METHODS: We identified patients who
      underwent a first or second myocardial revascularization between 1993 and 2004,
      and we arbitrarily divided them into 2 groups: 1 cohort of patients who underwent
      surgery between 1993 and 1998 and 1 cohort of patients who underwent surgery
      between 1999 and 2004. We compared demographic and clinical characteristics
      between the 2 cohorts and determined which variables were significant predictors
      of morbidity and mortality. RESULTS: From 1993 to 2004, 12 202 patients underwent
      a first (95.5%) or second (4.5%) myocardial revascularization. Patients in the
      later cohort presented with a high-risk profile. They were older and had
      metabolic syndrome or diabetes and peripheral vascular disease. On the other
      hand, there were fewer active smokers in this group. Whereas the rate of
      postoperative infarction and renal insufficiency was higher in the second cohort,
      this group had a lower incidence of stroke and prolonged mechanical ventilation
      and shorter hospital stays. Overall, observed mortality decreased in spite of a
      steady increase in predicted mortality. Identified predictors of mortality were
      age, stroke, female sex, nonelective surgery, renal insufficiency, peripheral
      vascular disease, chronic obstructive pulmonary disease, ventricular dysfunction
      and stenosis of the left main trunk. CONCLUSION: Our study confirmed current
      trends that show an increase in the at-risk population with dysmetabolic syndrome
      in cardiac surgery, as well as constant improvements in tertiary care in
      anesthesia and coronary surgery.

PMID- 19865575
TI  - Strategic faculty recruitment increases research productivity within an academic
      university division.
AB  - BACKGROUND: Research is an important mandate for academic surgical divisions.
      However, there is widespread concern that the current health care climate is
      leading to a decline in research activity. A University of British Columbia (UBC)
      academic surgical division attempted to address this concern by strategically
      recruiting PhD research scientists to prioritize research and develop
      collaborative research programs. The objective of our study was to determine
      whether this strategy resulted in increased research productivity. METHODS: We
      reviewed the UBC Department of Surgery database to assess research funding
      obtained by the Division of General Surgery for the years 1994-2004. We searched
      MEDLINE for peer-reviewed publications by faculty members during this period.
      RESULTS: Research funding increased from a mean of Can$417,292 per year in the 5
      years (1994/95-1998/99) before the recruitment of dedicated PhD scientists to a
      mean of Can$1.3 million per year in the 5 years following the recruitment
      strategy (1999/2000-2003/04; p = 0.012). Funding for the initial 5 years was
      Can$2.1 million, including 1 Canadian Institutes of Health Research (CIHR) grant.
      Funding increased to Can$6.8 million, including 22 CIHR grants over the
      subsequent 5 years (p < 0.001). Collaborative research led to the awarding of
      multidisciplinary grants exceeding Can$4 million with divisional members as
      principle or coprinciple investigators. From 1994/05 to 1998/99, the total number
      of peer-reviewed publications was 116 (mean 23.2, standard deviation [SD] 7 per
      year), increasing to 144 from 1999/2000 to 2003/04 (mean 28.8, SD 13 per year).
      The trend was for publications in journals with higher impact factors in the
      latter 5-year period. CONCLUSION: Strategic recruitment resulted in increased and
      sustained research productivity. Interactions between research scientists and
      clinicians resulted in successful program grant funding support. These results
      have implications for sustaining the research mission within academic departments
      of surgery.

PMID- 19865576
TI  - The management of treatment-resistant biliary calculi using percutaneous
      endourologic techniques.
AB  - BACKGROUND: Complicated choledocholithiasis cannot always be managed by standard
      surgical, radiologic or endoscopic methods. One additional approach is to use
      percutaneous techniques developed by endourologists to treat renal calculi. In
      this report, we present our experience over the past 10 years with this novel
      approach. METHODS: We conducted a retrospective review of all patients who
      underwent percutaneous, endoscopic treatment of biliary calculi at our
      institution between January 1997 and August 2007. Primary outcomes of interest
      were symptom- and stone-free rates, length of stay in hospital and complications.
      RESULTS: Nineteen patients underwent 21 percutaneous treatments for biliary
      calculi. All were dependent on external drainage for symptom control. The primary
      indications for treatment were cholangitis, retained stone, biliary colic and
      jaundice. Seventeen patients (89.5%) had failed prior endoscopic retrograde
      cholangiopancreatography (ERCP) or open attempts at treatment. The 2 remaining
      patients (10.5%) were deemed unfit for a general anesthetic. Patients had
      experienced a mean of 1.8 (standard deviation [SD] 1.0) prior failed attempts at
      stone removal. We used several treatment modalities, including holmium:yttrium
      aluminum-garnet laser (61.9%), electrohydraulic lithotripter (19.0%), ultrasound
      (9.5%), basket extraction (9.5%) and balloon dilatation of the ampulla (19.0%).
      Overall, treatment led to successful removal of the biliary drainage tube in
      94.7% of patients and 76.2% were stone-free. We performed cholangiograms an
      average of 21.8 (SD 13.7) days after treatment. The average length of stay in
      hospital was 1.9 (SD 1.1) days. One patient experienced a perioperative acute
      coronary syndrome and another experienced prolonged biliary drainage. Both had
      successful endoscopic treatment of their calculi. There were no cases of
      treatment-related sepsis, and we observed no other complications. CONCLUSION:
      Biliary calculi may be successfully treated using standard endourologic methods
      with high stone-free rates. This technique is generally well-tolerated even among
      high-risk patients.

PMID- 19865577
TI  - Outcomes of total joint arthroplasty in academic versus community hospitals.
AB  - BACKGROUND: Most joint-replacement surgeries are currently performed in community
      hospitals. We sought to determine whether the functional outcomes of joint
      replacement surgery differ between academic and community hospitals. METHODS: We
      surveyed 471 patients for demographic data, Western Ontario McMaster University
      Osteoarthritis Index (WOMAC) scores and Medical Outcomes Study Short Form 36 (SF
      36) scores at baseline and at 3-month and 1-year follow-up. We assessed patient
      satisfaction at 1 year with a single survey question. RESULTS: Community hospital
      patients (n = 269) were significantly older and had greater comorbidity than
      academic hospital patients (n = 202; p < 0.05). We found no difference in WOMAC
      scores, SF-36 scores or in patient satisfaction between hospitals at 1-year
      follow-up (p > 0.05). Adjusted analysis showed that patients undergoing surgery
      in an academic or community hospitals have the same functional outcomes.
      CONCLUSION: There is no significant difference in the functional outcomes of
      joint-replacement surgery between academic and community hospitals. Further work
      will involve evaluating cost of care differences between these types of
      hospitals.

PMID- 19865578
TI  - Clinical management of cocaine body packers: the Hillingdon experience.
AB  - BACKGROUND: International smuggling of cocaine by internal concealment is a
      serious and growing problem. People who engage in this practice are commonly
      referred to as body packers or mules. The most serious risks associated with body
      packing include intestinal obstruction and death from cocaine intoxication. These
      patients were previously managed primarily by surgical retrieval. This was
      associated with significant mortality due to rupture of poorly constructed
      cocaine packages. More recently, conservative management using whole bowel
      irrigation with polyethylene-glycol (Klean-prep Norgine) has been shown to be
      safe for most patients. To date, however, a consistent approach for the
      management of these patients has not been established. METHODS: We
      retrospectively reviewed the case notes, prescription charts and radiological
      investigations of all body packers admitted to our unit between 2000 and 2005,
      concentrating on initial management, complications and outcome. RESULTS: We
      identified 61 patients for inclusion. Of these, 56 were managed conservatively
      with a selection of aperients and laxatives. Six patients were treated
      successfully for cocaine toxicity and 5 required surgical retrieval of cocaine
      packets. CONCLUSION: Our results confirm the safety of a conservative approach.
      Based on our experience and a review of the literature, we have devised a
      treatment protocol to reduce the risk of complications and the length of stay in
      hospital.

PMID- 19865579
TI  - Complementary and alternative medicine use among general surgery, hepatobiliary
      surgery and surgical oncology patients.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) is becoming
      more common, particularly among cancer patients. We sought to define the
      frequency of CAM use among general surgery, hepatobiliary and surgical oncology
      patients and to define some of the determinants of CAM use in patients with
      benign and malignant disease. METHODS: We asked all patients attending the
      clinics of 3 hepatobiliary/surgical oncology surgeons from 2002 to 2005 to
      voluntarily respond on first and subsequent visits to a questionnaire related to
      the use of CAM. We randomly selected patients for review. RESULTS: We reviewed a
      total of 490 surveys from 357 patients. Overall CAM use was 27%. There was
      significantly more CAM use among cancer (34%) versus noncancer patients (21%; p =
      0.008), and the use of CAM was more common in patients with unresectable cancer
      (51%) than resectable cancer (22%; p < 0.001). There was no significant
      difference in use between men and women. There did not appear to be a change in
      CAM use with progression of cancer. The most common CAM was herbs or supplements
      (58% of all users), which were most frequently used by patients with malignant
      disease. Among the 27 herbs reported to be ingested, 10 are associated with
      bleeding and hepatotoxicity, as described in the literature. CONCLUSION:
      Prospective studies evaluating surgical outcomes related to CAM use are needed.

PMID- 19865580
TI  - Tracheostomy: from insertion to decannulation.
AB  - Tracheostomy is a common surgical procedure, and is increasingly performed in the
      intensive care unit (ICU) as opposed to the operating room. Procedural knowledge
      is essential and is therefore outlined in this review. We also review several
      high-quality studies comparing percutaneous dilational tracheostomy and open
      surgical tracheostomy. The percutaneous method has a comparable, if not superior,
      safety profile and lower cost compared with the open surgical approach; therefore
      the percutaneous method is increasingly chosen. Studies comparing early versus
      late tracheostomy suggest morbidity benefits that include less nosocomial
      pneumonia, shorter mechanical ventilation and shorter stay in the ICU. However,
      we discuss the questions that remain regarding the optimal timing of
      tracheostomy. We outline the potential acute and chronic complications of
      tracheostomy and their management, and we review the different tracheostomy
      tubes, their indications and when to remove them.

PMID- 19865582
TI  - CAGS and ACS Evidence-based reviews in surgery. 30: Prophylactic antibiotics for
      mesh inguinal hernioplasty.

PMID- 19865584
TI  - Incisional endometriosis: a report of 3 cases.

PMID- 19865581
TI  - Choledochal cysts: part 1 of 3: classification and pathogenesis.
AB  - Much about the etiology, pathophysiology, natural course and optimal treatment of
      cystic disease of the biliary tree remains under debate. Gastroenterologists,
      surgeons and radiologists alike still strive to optimize their roles in the
      management of choledochal cysts. To that end, much has been written about this
      disease entity, and the purpose of this 3-part review is to organize the
      available literature and present the various theories currently argued by the
      experts. In part 1, we discuss the background of the disease, describing the
      etiology, classification, pathogenesis and malignant potential of choledochal
      cysts.

PMID- 19865585
TI  - The Parent-into-F1 Model of Graft-vs-Host Disease as a Model of In Vivo T Cell
      Function and Immunomodulation.
AB  - Since its description roughly 30 years ago, the parent-into-F1 model of graft-vs.
      host disease has provided insights into the mechanisms of in vivo T cell
      activation and the pathogenesis of autoimmune conditions. A new and emerging role
      for the P-->F1 model is one of identifying agents with immunomodulatory activity
      and defining in vivo mechanisms that promote cell mediated or antibody mediated
      immune responses. Because F1 mice are not irradiated prior to donor cell
      transfer, the P-->F1 model has in the past not been strictly analogous to human
      hematopoetic stem cell transplantation. However with the advent of newer non
      myeloablative conditioning regimens, the model may assume more relevance. In this
      article, we first provide a review of relevant earlier fundamental observations
      followed by a summary of recent work from our laboratory in which acute and
      chronic GVHD in this model have been used not only to study normal T cell
      responses in vivo but also to define mechanisms important in the pathogenesis of
      autoimmunity and immunomodulation.

PMID- 19865586
TI  - FLOW DYNAMIC COMPARISON BETWEEN RECESSED HINGE AND OPEN PIVOT BI-LEAFLET HEART
      VALVE DESIGNS.
AB  - The flow dynamics through the peripheral and hinge regions of a bi-leaflet
      mechanical heart valve are complex and result in abnormally high shear stresses
      particularly during the closing phase of the valve function. It has been observed
      that, the late stages of closure is more significant in the dynamics of platelet
      activation; therefore, the later stages of closure is simulated by solving the
      two-dimensional Navier-Stokes equations using an Eulerian Levelset based sharp
      interface Cartesian grid method. Using a fixed Cartesian mesh incorporating local
      mesh refinement for solution accuracy and efficiency, the flow through and within
      a recessed hinge design and an open pivot hinge design is compared. Platelets are
      modelled as point particles by Lagrangian particle tracking algorithm with one
      way coupling. A dilute particle flow is assumed and particle-particle
      interactions are neglected. It was observed that the hinge region of the open
      pivot valve indicated a lower potential for activation of platelets compared to
      that in valves with a recessed hinge design.

PMID- 19865587
TI  - Nanoparticle Formulation Increases Oral Bioavailability of Poorly Soluble Drugs:
      Approaches Experimental Evidences and Theory.
AB  - The increasing frequency at which poorly soluble new chemical entities are being
      discovered raises concerns in the pharmaceutical industry about drugability
      associated with erratic dissolution and low bioavailability of these hydrophobic
      compounds. Nanonization provides a plausible pharmaceutical basis for enhancing
      oral bioavailability and therapeutic effectiveness of these compounds by
      increasing their surface area. This paper surveys methods available to
      pharmaceutical manufacturing nanoparticles, including wet chemical processes,
      media milling, high pressure homogenization, gas-phase synthesis, and form-in
      place processes, and elaborates physicochemical rational and gastrointestinal
      physiological basis upon which nano-drugs can be readily absorbed. Relevant
      examples are illustrated to show that nano-drugs permeate Caco-2 cell monolayer
      fast and are well absorbed into animal systemic circulation with high T(max) and
      AUC, resulting in oral bioavailability higher than their counterpart micro-drugs.
      The size-dependent permeability and bioavailability should be given particular
      consideration in the development of potent and selective drug candidates with
      poor aqueous solubility.

PMID- 19865588
TI  - Effect of Bronchial Thermoplasty on Airway Closure.
AB  - BACKGROUND: Bronchial Thermoplasty, a procedure that applies thermal energy to
      the airway wall has been shown to impair the ability of airway to contract in
      response to methacholine chloride (Mch). The technique has been advocated as an
      alternative treatment for asthma that may permanently limit airway narrowing. In
      previous experimental studies in dogs and humans, it was shown that those airways
      treated with bronchial thermoplasty had significant impairment of Mch
      responsiveness. METHODS: In the present study, we investigated the ability of
      canine airways to close completely with very high concentrations of Mch after
      bronchial thermoplasty. Bronchial thermoplasty was performed on dogs using the
      Alair System, comprising a low power RF controller and a basket catheter with
      four electrodes. A local atomization of Mch agonist was delivered directly to the
      epithelium of the same airway locations with repeated challenges. Airway size was
      measured with computed tomography, and closure was considered to occur in any
      airway where the lumen fell below the resolution of the scanner (< 1 mm).
      RESULTS: Our results show that, while treated airways still have the capacity to
      close at very high doses of Mch, this ability is seriously impaired after
      treatment, requiring much higher doses. CONCLUSIONS: Bronchial thermoplasty as
      currently applied seems to simply shift the entire dose response curve toward
      increasing airway size. Thus, this procedure simply serves to minimize the
      ability of airways to narrow under any level of stimulation.

PMID- 19865589
TI  - Exhaustive Enumeration of Kinetic Model Topologies for the Analysis of Time
      Resolved RNA Folding.
AB  - Unlike protein folding, the process by which a large RNA molecule adopts a
      functionally active conformation remains poorly understood. Chemical mapping
      techniques, such as Hydroxyl Radical (.OH) footprinting report on local
      structural changes in an RNA as it folds with single nucleotide resolution. The
      analysis and interpretation of this kinetic data requires the identification and
      subsequent optimization of a kinetic model and its parameters. We detail our
      approach to this problem, specifically focusing on a novel strategy to overcome a
      factorial explosion in the number of possible models that need to be tested to
      identify the best fitting model. Previously, smaller systems (less than three
      intermediates) were computationally tractable using a distributed computing
      approach. However, for larger systems with three or more intermediates, the
      problem became computationally intractable. With our new enumeration strategy, we
      are able to significantly reduce the number of models that need to be tested
      using non-linear least squares optimization, allowing us to study systems with up
      to five intermediates. Furthermore, two intermediate systems can now be analyzed
      on a desktop computer, which eliminates the need for a distributed computing
      solution for most medium-sized data sets. Our new approach also allows us to
      study potential degeneracy in kinetic model selection, elucidating the limits of
      the method when working with large systems. This work establishes clear criteria
      for determining if experimental .OH data is sufficient to determine the
      underlying kinetic model, or if other experimental modalities are required to
      resolve any degeneracy.

PMID- 19865590
TI  - Fast Computation by Block Permanents of Cumulative Distribution Functions of
      Order Statistics from Several Populations.
AB  - The joint cumulative distribution function for order statistics arising from
      several different populations is given in terms of the distribution functions of
      the populations. The computational cost of our formula in the case of two
      populations is still exponential in the worst case, but it is a dramatic
      improvement compared to the general formula by Bapat and Beg. In the case when
      only the joint distribution function of a subset of the order statistics of fixed
      size is needed, the complexity is polynomial, for the case of two populations.

PMID- 19865591
TI  - Couples Counseling in Alzheimer's Disease: Additional Clinical Findings from a
      Novel Intervention Study.
AB  - This article describes the clinical findings of a study designed to assess the
      benefit of counseling for couples, one of whom is in the early stage of
      Alzheimer's disease (AD). We previously reported our findings based on the first
      12 couples that enrolled in the study. Based on the treatment of 30 additional
      couples, we have refined our treatment strategy to include concepts of Gestalt
      Therapy and Transactional Analysis and identified prevalent issues of concern to
      this cohort. The study design has remained as described in the earlier article
      (Epstein et al., 2006), and has proven to be appropriate to meet the goals of
      this intervention as indicated by our clinical experience and feedback from the
      participating couples. Case vignettes demonstrate how to conduct the sessions so
      that the experience of each member of the dyad is validated, while acknowledging
      the differential impact of the disease on them.

PMID- 19865592
TI  - Genomic promoter analysis predicts functional transcription factor binding.
AB  - Background. The computational identification of functional transcription factor
      binding sites (TFBSs) remains a major challenge of computational biology.
      Results. We have analyzed the conserved promoter sequences for the complete set
      of human RefSeq genes using our conserved transcription factor binding site
      (CONFAC) software. CONFAC identified 16296 human-mouse ortholog gene pairs, and
      of those pairs, 9107 genes contained conserved TFBS in the 3 kb proximal promoter
      and first intron. To attempt to predict in vivo occupancy of transcription factor
      binding sites, we developed a novel marginal effect isolator algorithm that
      builds upon Bayesian methods for multigroup TFBS filtering and predicted the in
      vivo occupancy of two transcription factors with an overall accuracy of 84%.
      Conclusion. Our analyses show that integration of chromatin immunoprecipitation
      data with conserved TFBS analysis can be used to generate accurate predictions of
      functional TFBS. They also show that TFBS cooccurrence can be used to predict
      transcription factor binding to promoters in vivo.

PMID- 19865593
TI  - Preparation of Disubstituted Phenyl Propargyl Alcohols, their Use in Oxathiolene
      Oxide Synthesis, and Evaluation of the Oxathiolene Oxide Products as
      Anticarcinogenic Enzyme Inducers.
AB  - A number of alkynols have been prepared by Sonogoshira coupling of propargyl
      alcohol to disubstituted aromatic halides. Chelation controlled addition of
      organometallic nucleophiles to these alkynols was then affected followed by the
      addition of sulfur dioxide. This methodology was used to prepare a number of
      oxathiolene oxides which have been screened as NQO1 (quinone oxidoreductase)
      inducers.

PMID- 19865594
TI  - Demographic Change, Social Security Systems, and Savings.
AB  - In theory, improvements in healthy life expectancy should generate increases in
      the average age of retirement, with little effect on savings rates. In many
      countries, however, retirement incentives in social security programs prevent
      retirement ages from keeping pace with changes in life expectancy, leading to an
      increased need for life-cycle savings. Analyzing a cross-country panel of
      macroeconomic data, we find that increased longevity raises aggregate savings
      rates in countries with universal pension coverage and retirement incentives,
      though the effect disappears in countries with pay-as-you-go systems and high
      replacement rates.

PMID- 19865595
TI  - Culture and the Behavioral Manifestations of Traits: An Application of the Act
      Frequency Approach.
AB  - The behavioral manifestations of Big Five traits were compared across cultures
      using the Act Frequency Approach. American (n = 176) and Filipino (n = 195)
      students completed a Big Five measure and act frequency ratings for behaviors
      performed during the past month. Acts for specific traits cohered to an
      equivalent degree across cultures. In both cultures, the structure of act
      composites resembled the Big Five and the strength of trait-behavior
      relationships was very similar. Many acts were multidimensional and analyses
      revealed cultural commonalities and differences in the relevance and prevalence
      of acts for the Big Five traits. The results were more consistent with trait than
      cultural psychology perspectives, because traits predicted behavior equally well,
      on average, in the two cultures.

PMID- 19865596
TI  - Rho signaling mediates cytoskeletal re-arrangements in octopus photoreceptors.
AB  - Light sensitive rhabdoms in the octopus retina increase in cross-sectional area
      in the dark and shrink in the light. Growth in the dark is due to the formation
      of microvilli in an avillar region of the photoreceptor cell membrane and
      lengthening of rhabdomere microvilli already present. Diminution in the light is
      the result of the disassembly and shortening of the same microvilli. Each
      microvillus contains an actin filament core that must be assembled or
      disassembled in the dark or light, respectively. To understand the regulation of
      the construction and breakdown of rhabdomere microvilli in the light and dark, we
      used centrifugation to separate the rhabdom membranes followed by Western
      blotting and Rho pull-down assays to investigate the role of Rho GTPases in this
      process. Western blotting showed a difference in the distribution of Rho in
      rhabdom membrane and supernatant fractions. In the light, Rho was mostly present
      in the supernatant but in the dark it was found in the fraction enriched with
      rhabdom membranes. Complementing these results, pull-down assays showed that Rho
      is activated in the dark but in the light, Rho is mostly inactive. We believe
      that in the dark, activated Rho binds to the rhabdom membrane and initiates
      signaling pathways, leading to growth of rhabdomere microvilli. In the light, Rho
      is present in the soluble fraction, is inactivated, and is likely bound to a Rho
      GDI. Receptors involved in the activation of Rho in the dark are undetermined and
      may involve rhodopsin or another membrane protein.

PMID- 19865597
TI  - Simultaneous Border Segmentation of Doughnut-Shaped Objects in Medical Images.
AB  - Image segmentation with specific constraints has found applications in several
      areas such as biomedical image analysis and data mining. In this paper, we study
      the problem of simultaneous detection of both borders of a doughnut-shaped and
      smooth objects in 2-D medical images. Image objects of that shape are often
      studied in medical applications. We present an O(IJU(U-L)logJUlog(U-L)) time
      algorithm, where the size of the input 2-D image is I x J, M is the smoothness
      parameter with 1 </= M </= J, and L and U are the thickness parameters specifying
      the thickness between two border contours of a doughnut-shaped object. Previous
      approaches for solving this segmentation problem are computationally expensive
      and/or need a lot of user interference. Our algorithm improves the
      straightforward dynamic programming algorithm by a factor of O(J(U
      L)M2UlogJUlog(U-L)). We explore some interesting observations, which make
      possible to apply the divide-and-conquer strategy combined with dynamic
      programming. Our algorithm is also based on computing optimal paths in an
      implicitly represented graph.

PMID- 19865598
TI  - Domains of Risk in the Developmental Continuity of Fire Setting.
AB  - Juvenile fire setting is a serious, dangerous, and costly behavior. The majority
      of research examining youth fire setting has been cross-sectional. We sought to
      examine early risk attributes that could differentiate fire setters from non-fire
      setters, in addition to examining their association with the developmental
      continuity of fire-setting behavior into late childhood. Using a sample of 361
      youth drawn from 4 different U.S. communities, this study examined the
      association between a broad array of risk variables from the child, parent, and
      family domains, and fire-setting behavior over the course of 2 developmental
      periods: prior to 4th grade, and between 4th and 6th grade. Youth were classified
      into I of 4 groups (non-fire setters, desisters, later-onset fire setters, and
      persisters) based on their reported fire-setting behavior during these periods.
      Children who set fires had higher levels of risk on most of the variables
      assessed. Persistence of fire setting was associated with elevated parental
      depressive symptoms and more interparental conflict and ineffective discipline.
      The findings highlight the need for multi-component preventive interventions to
      address the breadth of risk experienced by fire-setting youth and their families.

PMID- 19865599
TI  - On VLSI Design of Rank-Order Filtering using DCRAM Architecture.
AB  - This paper addresses on VLSI design of rank-order filtering (ROF) with a maskable
      memory for real-time speech and image processing applications. Based on a generic
      bit-sliced ROF algorithm, the proposed design uses a special-defined memory,
      called the dual-cell random-access memory (DCRAM), to realize major operations of
      ROF: threshold decomposition and polarization. Using the memory-oriented
      architecture, the proposed ROF processor can benefit from high flexibility, low
      cost and high speed. The DCRAM can perform the bit-sliced read, partial write,
      and pipelined processing. The bit-sliced read and partial write are driven by
      maskable registers. With recursive execution of the bit-slicing read and partial
      write, the DCRAM can effectively realize ROF in terms of cost and speed. The
      proposed design has been implemented using TSMC 0.18 MUm 1P6M technology. As
      shown in the result of physical implementation, the core size is 356.1 *
      427.7MUm(2) and the VLSI implementation of ROF can operate at 256 MHz for 1.8V
      supply.

PMID- 19865600
TI  - Remediating Number Combination and Word Problem Deficits Among Students With
      Mathematics Difficulties: A Randomized Control Trial.
AB  - The purposes of this study were to assess the efficacy of remedial tutoring for
      3rd graders with mathematics difficulty, to investigate whether tutoring is
      differentially efficacious depending on students' math difficulty status
      (mathematics difficulty alone vs. mathematics plus reading difficulty), to
      explore transfer from number combination (NC) remediation, and to examine the
      transportability of the tutoring protocols. At 2 sites, 133 students were
      stratified on mathematics difficulty status and site and then randomly assigned
      to 3 conditions: control (no tutoring), tutoring on automatic retrieval of NCs
      (i.e., Math Flash), or tutoring on word problems with attention to the
      foundational skills of NCs, procedural calculations, and algebra (i.e., Pirate
      Math). Tutoring occurred for 16 weeks, 3 sessions per week and 20-30 min per
      session. Math Flash enhanced fluency with NCs with transfer to procedural
      computation but without transfer to algebra or word problems. Pirate Math
      enhanced word problem skill as well as fluency with NCs, procedural computation,
      and algebra. Tutoring was not differentially efficacious as a function of
      students' mathematics difficulty status. The tutoring protocols proved
      transportable across sites.

PMID- 19865601
TI  - Antimicrobial efficacy and ocular cell toxicity from silver nanoparticles.
AB  - Silver in various forms has long been recognized for antimicrobial properties,
      both in biomedical devices and in eyes. However, soluble drugs used on the ocular
      surface are rapidly cleared through tear ducts and eventually ingested, resulting
      in decreased efficacy of the drug on its target tissue and potential concern for
      systemic side effects. Silver nanoparticles were studied as a source of anti
      microbial silver for possible controlled-release contact lens controlled delivery
      formulations. Silver ion release over a period of several weeks from nanoparticle
      sources of various sizes and doses in vitro was evaluated in vitro against
      Pseudomonas aeruginosa strain PA01. Mammalian cell viability and cytokine
      expression in response to silver nanoparticle exposure is evaluated using corneal
      epithelial cells and eye-associated macrophages cultured in vitro in serum-free
      media. Minimal microcidal and cell toxic effects were observed for several silver
      nanoparticle suspensions and aqueous extraction times for bulk total silver
      concentrations commensurate with comparative silver ion (e.g., Ag(+) ((aq)))
      toxicity. This indicates that (1) silver particles themselves are not microcidal
      under conditions tested, and (2) insufficient silver ion is generated from these
      particles at these loadings to produce observable biological effects in these in
      vitro assays. If dosing allows substantially increased silver particle loading in
      the lens, the bactericidal efficacy of silver nanoparticles in vitro is one
      possible approach to limiting bacterial colonization problems associated with
      extended-wear contact lenses.

PMID- 19865602
TI  - TIME DELAY SYSTEMS WITH DISTRIBUTION DEPENDENT DYNAMICS.
AB  - General delay dynamical systems in which uncertainty is present in the form of
      probability measure dependent dynamics are considered. Several motivating
      examples arising in biology are discussed. A functional analytic framework for
      investigating well-posedness (existence, uniqueness and continuous dependence of
      solutions), inverse problems, sensitivity analysis and approximations of the
      measures for computational purposes is surveyed.

PMID- 19865603
TI  - On Quantitizing.
AB  - Quantitizing, commonly understood to refer to the numerical translation,
      transformation, or conversion of qualitative data, has become a staple of mixed
      methods research. Typically glossed are the foundational assumptions, judgments,
      and compromises involved in converting disparate data sets into each other and
      whether such conversions advance inquiry. Among these assumptions are that
      qualitative and quantitative data constitute two kinds of data, that quantitizing
      constitutes a unidirectional process essentially different from qualitizing, and
      that counting is an unambiguous process. Among the judgments are deciding what
      and how to count. Among the compromises are balancing numerical precision with
      narrative complexity. The standpoints of "conditional complementarity," "critical
      remediation," and "analytic alternation" clarify the added value of converting
      qualitative data into quantitative form.

PMID- 19865604
TI  - Interactions Between Cultured Neurons and Carbon Nanotubes: A Nanoneuroscience
      Vignette.
AB  - Carbon nanotubes, owing to their electrical, chemical, mechanical, and thermal
      properties, are one of the most promising nanomaterials for the electronics,
      computer, and aerospace industries. More recently, these unique materials are
      finding their niche in neuroscience. Here, we discuss the use of carbon nanotubes
      as scaffolds for neuronal growth. The chemical properties of carbon nanotubes can
      be systematically varied by attaching different functional groups. Such
      functionalized carbon nanotubes can be used to control the outgrowth and
      branching pattern of neuronal processes. We also discuss electrical interactions
      between neurons and carbon nanotubes. The electrical properties of nanotubes can
      provide a mechanism to monitor or stimulate neurons through the scaffold itself.
      The ease of which carbon nanotubes can be patterned makes them attractive for
      studying the organization of neural networks and has the potential to develop new
      devices for neural prosthesis. We note that additional toxicity studies of carbon
      nanotubes are necessary so that exposure guidelines and safety regulations can be
      set.

PMID- 19865605
TI  - Life satisfaction across adulthood: different determinants at different ages?
AB  - It is likely that with aging and changing life circumstances, individuals' values
      shift in systematic ways, and that these shifts may be accompanied by shifts in
      the determinants of their subjective judgments of well being. To examine this
      possibility, the relations among the Satisfaction With Life Scale (SWLS) and a
      number of personality, affect, demographic, and cognitive variables were examined
      in a sample of 818 participants between the ages of 18 and 94. The results
      indicated that although many variables had significant zero-order correlations
      with the SWLS, only a few variables had unique utility in predicting life
      satisfaction. Invariance analyses indicated that while the qualitative nature of
      life satisfaction remains constant across adult age, the influence of fluid
      intelligence on judgments of life satisfaction declines with age. In contrast,
      negative affect is negatively associated with life satisfaction consistently
      across the adult age span.

PMID- 19865606
TI  - The Mechanism of Budding of Retroviruses From Cell Membranes.
AB  - Retroviruses have evolved a mechanism for the release of particles from the cell
      membrane that appropriates cellular protein complexes, referred to as ESCRT-I, 
      II, -III, normally involved in the biogenesis of multivesicular bodies. Three
      different classes of late assembly (L) domains encoded in Gag, with core
      sequences of PPXY, PTAP, and YPXL, recruit different components of the ESCRT
      machinery to form a budding complex for virus release. Here, we highlight recent
      progress in identifying the role of different ESCRT complexes in facilitating
      budding, ubiquitination, and membrane targeting of avian sarcoma and leukosis
      virus (ASLV) and human immunodeficiency virus, type 1 (HIV-1). These findings
      show that retroviruses adopt parallel budding pathways by recruiting different
      host factors from common cellular machinery for particle release.

PMID- 19865607
TI  - The Relation of Cumulative Demographic Risk to Mothers' Responsivity and Control:
      Examining the Role of Toddler Temperament.
AB  - The relations of cumulative demographic risk and children's temperament to
      mothers' parenting behaviors were examined when children were 18 (T1, n = 247)
      and 30 (T2, n = 216) months of age. Mothers, nonparental caregivers (e.g., child
      care providers), and observers reported on children's temperament to create a
      temperament composite, and mothers reported on demographic risk variables.
      Maternal responsivity and control were observed during 2 mother-child
      interactions at both time points. Cumulative demographic risk was related to low
      maternal responsivity concurrently and longitudinally, even after controlling for
      earlier temperament and responsivity, and demographic risk was positively related
      to maternal control at T1 and T2. Regulated temperament (i.e., low frustration
      and high regulation) was linked with high maternal responsivity at T1 and T2 and
      low maternal control at T2. Moreover, the positive relation between cumulative
      risk and maternal control at T1 was stronger when children were viewed as less
      regulated.

PMID- 19865608
TI  - ABC's and 123's: Parental Literacy, Numeracy, and Childhood Obesity.

PMID- 19865609
TI  - Effects of Familism and Family Cohesion on Problem Behaviors among Adolescents in
      Mexican Immigrant Families in the Southwest U.S.
AB  - This study used baseline data from the Southwest sample of the Latino
      Acculturation and Health project to examine whether familism and cohesion are
      related to problem behaviors in a sample of Mexican and Mexican American
      adolescents in the Southwest U.S. This study is important to practitioners, and
      prevention and intervention researchers because it examines buffers to problem
      behaviors among an increasingly at-risk population. The results confirm that
      familism is a powerful protective factor against aggressive behavior, conduct
      problems and rule breaking in this sample. The results draw attention to the
      importance of family among Mexican and Mexican American families. Family
      cohesion, however, was found to be protective against conduct problems and rule
      breaking but not aggressive behavior. Possible explanations for this result are
      discussed. Additional findings suggest that adolescents who have the ability to
      navigate between culture of origin and mainstream culture are also protected
      against some problem behaviors.

PMID- 19865610
TI  - Converging Streams of Opportunity for Prison Nursery Programs in the United
      States.
AB  - Prison nursery programs allow departments of correction to positively intervene
      in the lives of both incarcerated mothers and their infant children. The number
      of prison nurseries in the United States has risen dramatically in the past
      decade, yet there remains a significant gap between predominant correctional
      policy in this area and what is known about parenting and infant development.
      Using Kingdon's streams metaphor, this article examines the recent convergence of
      problem, policy, and political events related to incarcerated women with infant
      children and argues that this has created a window of opportunity for development
      of prison nursery programs. Aday's policy analysis criteria are also used to
      analyze available evidence regarding the effectiveness, efficiency, and equity of
      prison nursery programs as policy alternatives for incarcerated women with infant
      children.

PMID- 19865611
TI  - An Essay on Understanding the Mind.
AB  - Several conjectures by A. S. Iberall on life and mind are used as a backdrop to
      sketch a theory of mental activity that respects both the contents of thought and
      the dynamics of thinking. The dynamics, in this case, refers fundamentally to
      animated, meaningfully coupled self-organizing processes (coordination dynamics)
      and exhibit multistability, switching, and, because of symmetry breaking,
      metastability. The interplay of 2 simultaneously acting forces underlies the
      metastable mind: the tendency for the coordinating elements to couple together
      (integration) and the tendency for the elements to express their individual
      autonomy (segregation). Metrics for metastability are introduced that enable
      these cooperative and competitive tendencies to be quantified. Whereas
      bistability is the basis for polarized, either/or thinking, the metastable regime
      which contains neither stable nor unstable states, no states at all, in fact
      gives rise to a far more fluid, complementary mode of operation in which it is
      possible for apparent contraries to coexist in the mind at the same time.

PMID- 19865612
TI  - A solution to limitations of cognitive testing in children with intellectual
      disabilities: the case of fragile X syndrome.
AB  - Intelligence testing in children with intellectual disabilities (ID) has
      significant limitations. The normative samples of widely used intelligence tests,
      such as the Wechsler Intelligence Scales, rarely include an adequate number of
      subjects with ID needed to provide sensitive measurement in the very low ability
      range, and they are highly subject to floor effects. The IQ measurement problems
      in these children prevent characterization of strengths and weaknesses, poorer
      estimates of cognitive abilities in research applications, and in clinical
      settings, limited utility for assessment, prognosis estimation, and planning
      intervention. Here, we examined the sensitivity of the Wechsler Intelligence
      Scale for Children (WISC-III) in a large sample of children with fragile X
      syndrome (FXS), the most common cause of inherited ID. The WISC-III was
      administered to 217 children with FXS (age 6-17 years, 83 girls and 134 boys).
      Using raw norms data obtained with permission from the Psychological Corporation,
      we calculated normalized scores representing each participant's actual deviation
      from the standardization sample using a z-score transformation. To validate this
      approach, we compared correlations between the new normalized scores versus the
      usual standard scores with a measure of adaptive behavior (Vineland Adaptive
      Behavior Scales) and with a genetic measure specific to FXS (FMR1 protein or
      FMRP). The distribution of WISC-III standard scores showed significant skewing
      with floor effects in a high proportion of participants, especially males (64.9%
      94.0% across subtests). With the z-score normalization, the flooring problems
      were eliminated and scores were normally distributed. Furthermore, we found
      correlations between cognitive performance and adaptive behavior, and between
      cognition and FMRP that were very much improved when using these normalized
      scores in contrast to the usual standardized scores. The results of this study
      show that meaningful variation in intellectual ability in children with FXS, and
      probably other populations of children with neurodevelopmental disorders, is
      obscured by the usual translation of raw scores into standardized scores. A
      method of raw score transformation may improve the characterization of cognitive
      functioning in ID populations, especially for research applications.

PMID- 19865613
TI  - Effects of the Tumor-Leukocyte Microenvironment on Melanoma-Neutrophil Adhesion
      to the Endothelium in a Shear Flow.
AB  - The primary cause of cancer mortality is not attributed to primary tumor
      formation, but rather to the growth of metastases at distant organ sites. Tumor
      cell adhesion to blood vessel endothelium (EC) and subsequent transendothelial
      migration within the circulation are critical components of the metastasis
      cascade. Previous studies have shown polymorphonuclear neutrophils (PMNs) may
      facilitate melanoma cell adhesion to the EC and subsequent extravasation under
      flow conditions. The melanoma cell-PMN interactions are found to be mediated by
      the binding between intercellular adhesion molecule-1 (ICAM-1) on melanoma cells
      and beta(2) integrin on PMNs and by endogenously secreted interleukin 8 (IL-8)
      within the tumor-leukocyte microenvironment. In this study, the effects of fluid
      convection on the IL-8-mediated activation of PMNs and the binding kinetics
      between PMNs and melanoma cells were investigated. Results indicate that the
      shear rate dependence of PMN-melanoma cell adhesion and melanoma cell
      extravasation is due, at least partly, to the convection of tumor-secreted
      proinflammatory cytokine IL-8.

PMID- 19865614
TI  - Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose?
AB  - OBJECTIVE: Studies showing improved outcomes with tight glycemic control in the
      intensive care unit (ICU) have resulted in a substantial number of new insulin
      delivery algorithms being proposed. The present study highlights mechanisms used
      in the better-known approaches, examines what might be critical differences among
      them, and uses systems theory to characterize the conditions under which each can
      be expected to perform best. METHODS: Algorithm dose (DeltaI/DeltaG) and step
      (response to a persistent elevation in glucose) response curves were calculated
      for written instruction algorithms, developed at the Providence Heart and
      Vascular Institute (Portland [P] protocol), the University of Washington (UW),
      and Yale University (Y), together with similar curves for the Glucommander (GM)
      and proportional integral derivative (PID) computer algorithms. From the
      simulated curves, different mechanisms used to adjust insulin delivery were
      identified. RESULTS: All algorithms increased insulin delivery in response to
      persistent hyperglycemia, but the mechanism used altered the algorithm's
      sensitivity to glucose, or gain, in the GM, UW, and Y protocols, while leaving it
      unchanged for the P protocol and PID algorithm. CONCLUSIONS: The increase in
      insulin delivery in response to persistent hyperglycemia observed with all the
      algorithms can be expected to bring subjects who respond to insulin to targeted
      glucose ranges. However, because the PID and P protocols did not alter the
      insulin delivery response curves, these algorithms can be expected to take longer
      to achieve target glucose levels in individuals who are insulin resistant and/or
      are exposed to increased carbohydrate loads (e.g., glucose infusions). By
      contrast, the GM, UW, and Y algorithms can be expected to adapt to the insulin
      resistance such that the time to achieve target levels is unchanged if the time
      for insulin to act does not change. If the insulin resistance is accompanied by a
      longer time for insulin to act, the UW, Y, and GM algorithms may increase the
      risk of hypoglycemia. Under these conditions, the longer time required for the
      PID and P protocols to achieve a target glucose level may be a reasonable trade
      off for no increase in the risk of hypoglycemia.

PMID- 19865615
TI  - Improving quality of life through implant dentistry.

PMID- 19865617
TI  - Photoelastic analysis of stress patterns from different implant-abutment
      interfaces.
AB  - PURPOSE: To investigate the peri-implant stress fields generated from four
      different implant-abutment interfaces under axial loading applied at the center
      of the implant and several millimeters away from the implant center via
      photoelastic analysis. MATERIALS AND METHODS: Similar unthreaded and cylindric
      implants and abutments were fabricated and embedded in photoelastic resin with
      four different implant-abutment interfaces: external hex, internal hex, internal
      taper (11.5 degrees), and solid connection to the abutment (one piece). The
      samples were submitted to vertical compressive loads; one was applied at the
      implant center (1.5 kg; centered load), and the other was applied 6.5 mm away
      from the center, 4.4 mm from the outside of the outer aspect of the implant (0.75
      kg; off-centered load). The maximum shear stresses were determined and observed
      at 46 points around the implants under the centered load and at 61 points under
      the off-center load in the photoelastic models. Graphics describing the maximum
      shear stress (y-axis) and the analyzed points (x-axis) were obtained, and areas
      under the curves were calculated. RESULTS: The centered loading (all points)
      resulted in small differences. The lowest amounts of stress were observed for the
      internal-taper implants, and values were minimally greater (0.4% to 3.3%) for the
      other implants. No statistically significant differences were found between
      groups for the centered load in any area. Under an off-center load, the internal
      hex implants presented the least stress (all points). For off-center loading, the
      internal-hexagon implants differed significantly from the external-hex and one
      piece implants and displayed the lowest stress levels. CONCLUSION: Under an off
      center load, the internal-hex interfaces presented the lowest stress
      concentrations, internal-taper interfaces presented intermediate results, and one
      piece and external-hex implants resulted in high stress levels. Centralized axial
      loads produced similar results.

PMID- 19865618
TI  - Effect of electrochemically deposited nanohydroxyapatite on bone bonding of
      sandblasted/dual acid-etched titanium implant.
AB  - PURPOSE: The aim of this study was to evaluate the effect of an electrochemically
      deposited nanohydroxyapatite (EDHA) coating on the bone bonding of sandblasted
      and dual acid-etched titanium implants. MATERIALS AND METHODS: One hundred EDHA
      coated and uncoated sandblasted/dual acid-etched implants (3 mm in diameter, 10
      mm long) were inserted into the femoral condyles of 50 rabbits. The osteotomy
      sites were enlarged to 3 mm in diameter via a sequence of drills. After 2, 4, 6,
      8, and 12 weeks of bone healing, removal torque testing was performed to evaluate
      the interfacial shear strength of each implant type. The removed implants were
      prepared and observed with an electron microscope equipped with an energy
      dispersive electron probe x-ray microanalyzer. RESULTS: The mean removal torque
      values for the EDHA-coated implants were 39.6 Ncm at 2 weeks and 40.4 Ncm at 4
      weeks; corresponding values for the control implants were 21.1 Ncm and 24.1 Ncm.
      Removal torque values of the EDHA-coated implants were 87% higher than those of
      control implants after 2 weeks of healing (P = .015). However, the mean removal
      torque values for both types of implants were similar after 6, 8, or 12 weeks of
      healing (no significant differences between the implant surfaces; P > .05).
      CONCLUSIONS: The EDHA nanocrystal coating had a beneficial effect on interfacial
      shear strength during the early stages of bone healing.

PMID- 19865619
TI  - Rat model for studying tissue changes induced by the mechanical environment
      surrounding loaded titanium implants.
AB  - PURPOSE: This study presents a new rat oral implant model for assessing
      histologic changes in the mechanical environment surrounding loaded and unloaded
      dental implants. MATERIALS AND METHODS: The maxillary left first molar from
      retired breeder rats was extracted, and the site was allowed to heal for 1 month.
      A titanium miniscrew implant was then placed into the site and allowed to heal
      for 21 days. The mandibular left first molars in one group of rats were extracted
      to create an unloaded condition; in a second group of rats the mandibular left
      first molars were left in occlusion with the opposing screw head to simulate
      loading. Radiographs were taken on the day of placement and again at 7 days, 14
      days, and 21 days after placement and were used to estimate the bone-implant
      contact ratio. The rats were sacrificed after 21 days. Peri-implant tissue
      samples from day 21 were processed for histology and immunohistochemistry with
      antibodies to osteocalcin and matrix metalloproteinase 13 (MMP-13). Two
      dimensional finite element models were created from images of the histologic
      sections and immunohistochemical samples to observe tissue changes. RESULTS:
      Areas of high shear stress adjacent to the helical threads of loaded implants
      were associated with osteocalcin localization and bone formation but only minimal
      localization of MMP-13. Bone adjacent to unloaded implants showed fibrous tissue
      and extensive MMP-13 localization surrounding the apical two-thirds of each
      implant. These results agree with estimated bone-implant contact ratios, which
      showed a steady decrease in contact ratio for the unloaded implant group but a
      significantly higher contact ratio in the loaded group between 14 and 21 days.
      CONCLUSION: The rat oral implant model is useful for studies of the mechanical
      and physiologic environment affecting osseointegration in loaded and unloaded
      implants.

PMID- 19865620
TI  - The role of titanium implant surface modification with hydroxyapatite
      nanoparticles in progressive early bone-implant fixation in vivo.
AB  - PURPOSE: This study evaluated the biologic effect in vivo of hydroxyapatite (HA)
      nanoparticle surface modification on commercially pure titanium or titanium alloy
      (Ti-6Al-4V) implants. MATERIALS AND METHODS: Miniature cylindric titanium and Ti
      6Al-4V implants were pretreated with dual acid etching (DAE), and a subset was
      further modified with HA nanoparticles using discrete crystalline deposition
      (DCD). The resultant implant surface topography was characterized by
      interferometry and scanning electron microscopy. Miniature implants of DAE
      titanium, DAE Ti-6Al-4V, DCD titanium, and DCD Ti-6Al-4V were surgically placed
      in the femora of rats. After 4 days, 1 week, and 2 weeks of healing,
      osseointegration was evaluated by implant push-in tests or microcomputed
      tomography (microCT). Ti-6Al-4V samples were harvested at week 2 and prepared for
      nondecalcified histology and subjected to bone-to-implant contact (BIC)
      measurement. RESULTS: DCD treatment generated a complex surface morphology via
      the bonded HA nanoparticles. However, the amplitude and spatial, hybrid, and
      functional surface roughness parameters measured at the micron and submicron
      levels did not depict topographic differences between the DAE and the DCD
      modified implants. DAE titanium and DAE Ti-6Al-4V implants showed a sharp
      increase in push-in values at week 1, followed by a plateau at week 2. DCD
      titanium and DCD Ti-6Al-4V implants showed similar sharp increases at week 1, but
      the push-in values continued to increase at week 2. The surrounding bone
      architecture evaluated by microCT and the BIC ratio did not correlate with the
      biomechanical implant osseointegration measurement. CONCLUSIONS: DCD-derived
      surface modification with HA nanoparticles on titanium and Ti-6Al-4V implants
      resulted in progressive osseointegration profiles that were distinctively
      different from those of DAE controls. Surrogate measurements such as surface
      roughness parameters and BIC did not predict the biologic effect of the DCD
      treatment. The data indicate that early osseointegration may be more sensitively
      regulated by nanoscale surface characteristics.

PMID- 19865621
TI  - Gel-pressure technique for flapless transcrestal maxillary sinus floor elevation:
      a preliminary cadaveric study of a new surgical technique.
AB  - PURPOSE: To evaluate a novel surgical technique for flapless transcrestal
      elevation of the maxillary sinus floor via surgical templates using gel pressure.
      MATERIALS AND METHODS: Computed tomographic scans of fresh human cadaver maxillae
      and three-dimensional treatment planning software were used to design surgical
      templates. Access to the maxillary sinus was gained by guided transcrestal
      osteotomies to puncture the bony sinus floor. By injection of radiopaque gel, the
      maxillary sinus membrane was elevated to attain a postoperative bone height of 15
      mm. RESULTS: The gel-pressure technique was performed in 10 atrophic maxillary
      sites with a mean residual bone height of the alveolar crest of 4.7 +/- 1.6 mm.
      The sinus membrane was successfully elevated in all sites without causing
      iatrogenic perforation (mean elevation height, 10.6 +/- 1.6 mm). CONCLUSIONS: The
      gel-pressure technique may provide a new option for minimally invasive
      transcrestal sinus surgery and may represent a safe method to increase bone
      volume in the atrophic posterior maxilla.

PMID- 19865622
TI  - Accuracy of different impression techniques for internal-connection implants.
AB  - PURPOSE: This study evaluated the accuracy of four implant-level impression
      techniques with optical microscopy on two angulated conical internal-connection
      implants. MATERIALS AND METHODS: A master cast with two internal-connection
      implant analogs angulated 10 degrees from each other and a master framework were
      fabricated. Four impression techniques were examined: octagonal transfer
      impression coping, nonoctagonal transfer impression coping, nonoctagonal pickup
      impression coping, and nonoctagonal pickup impression copings joined together
      with autopolymerizing acrylic resin. Experimental casts were fabricated from 40
      polyether impressions divided into four groups. After the master framework was
      seated on each of the casts, one abutment screw was tightened and marginal gap
      measurements between analog and abutment were recorded on the other side with an
      optical microscope. RESULTS: The casts produced from nonoctagonal pickup
      impression techniques were more accurate than those produced using transfer
      impression techniques (P < .05). However, there was no statistically significant
      difference in the accuracy between the unsplinted and splinted methods in pickup
      impression techniques (P > .05) or between the use of octagonal coping and
      nonoctagonal coping in transfer impression techniques (P > .05). CONCLUSION: The
      casts produced from nonoctagonal pickup impression techniques were more accurate
      than those produced by transfer impression techniques, regardless of whether they
      were splinted, for angulated conical internal-connection implants.

PMID- 19865623
TI  - Biomechanical properties of jaw periosteum-derived mineralized culture on
      different titanium topography.
AB  - PURPOSE: This study evaluated the biomechanical properties of periosteum-derived
      mineralized culture on different surface topographies of titanium. MATERIALS AND
      METHODS: Titanium surfaces modified by machining or by acid etching were analyzed
      using scanning electron microscopy (SEM). Rat mandibular periosteum-derived cells
      were cultured on either of the titanium surfaces. Cell proliferation was
      evaluated by cell counts, and gene expression was analyzed using a reverse
      transcriptase polymerase chain reaction. Alkaline phosphatase (ALP) stain assay
      was employed to evaluate osteoblastic activity. Matrix mineralization was
      examined via von Kossa stain assay, total calcium deposition, and SEM. The
      hardness and elastic modulus of mineralized cultures were measured using a nano
      indenter. RESULTS: The machined surface demonstrated a flat topographic
      configuration, while the acid-etched surface revealed a uniform micron-scale
      roughness. Both cell density and ALP activity were significantly higher on the
      machined surface than on the acid-etched surface. The expression of bone-related
      genes was up-regulated or enhanced on the acid-etched surface compared to the
      machined surface. Von Kossa stain showed significantly greater positive areas for
      the machined surface compared to the acid-etched surface, while total calcium
      deposition was statistically similar. Mineralized culture on the acid-etched
      surface was characterized by denser calcium deposition, more mature collagen
      deposition on the superficial layer, and larger and denser globular matrices
      inside the matrix than the culture on the machined surface. The mineralized
      matrix on the acid-etched surface was two times harder than on the machined
      surface, whereas the elastic modulus was comparable between the two surfaces.
      CONCLUSIONS: The design of this study can be used as a model to evaluate the
      effect of implant surface topography on the biomechanical properties of
      periosteum-derived mineralized culture. The results suggest that mandibular
      periosteal cells respond to different titanium surface topographies differently
      enough to produce mineralized matrices with different biomechanical qualities.

PMID- 19865624
TI  - Influence of the length of the loading period after placement of orthodontic mini
      implants on changes in bone histomorphology: microcomputed tomographic and
      histologic analysis.
AB  - PURPOSE: The recent use of microcomputed tomography (microCT) has made it
      possible to analyze qualitative bone morphology at the implant surface and in the
      peri-implant region. The purpose of this study was to evaluate histomorphometric
      changes around the implant-bone interface after placement of mini-implants using
      three-dimensional microCT analysis and to compare the stability of the implants
      after immediate and early loads were applied. MATERIALS AND METHODS: Forty-eight
      orthodontic mini-implants (ORLUS, Ortholution) were placed in the mandibular
      buccal jawbone of eight beagle dogs. Force was applied immediately (immediate
      loading group) and 3 weeks (early loading group) after implant placement; control
      implants received no loading. An orthodontic force (250 to 300 g) was applied to
      the experimental implants for 3, 6, or 12 weeks before sacrifice. RESULTS: The
      bone-implant contact in both experimental groups was not significantly different
      for any loading period except for after 12 weeks of loading. The immediate
      loading group had higher bone volume percentages compared with the early loading
      group after 6 weeks, but there was no significant difference between groups after
      12 weeks. This was in accordance with the results of the three-dimensional
      microCT analysis. CONCLUSION: Histologic and microCT analysis showed that
      immediate loading of mini-implants in the dog model is possible for orthodontic
      applications with a high bone-implant contact and 100% survival rate.

PMID- 19865625
TI  - In vitro study of the influence of the type of connection on the fracture load of
      zirconia abutments with internal and external implant-abutment connections.
AB  - PURPOSE: To determine whether zirconia abutments with an internal connection
      exhibit similar fracture load as zirconia abutments with an external connection.
      MATERIALS AND METHODS: The following zirconia abutments were divided into four
      groups of 20 each: StraumannCARES abutments on Straumann implants (group A),
      Procera abutments on Branemark implants (group B), Procera abutments on
      NobelReplace implants (group C), and Zirabut SynOcta prototype abutments on
      Straumann implants (group D). The abutments were fixed on their respective
      implants either internally via a secondary abutment (A) or a metallic coupling
      (C) (two-piece) or directly externally (B) and internally (D) (one-piece). In
      each group, 10 abutments were left unrestored (A1 to D1). Ten received glass
      ceramic crowns (A2 to D2). Static loading was performed according to the ISO norm
      14801 until failure. The bending moment was calculated for comparison of the
      groups and subjected to statistical analysis (Student t test). RESULTS: The mean
      bending moments of the unrestored abutments were 371.5 +/- 142.3 Ncm (A1), 276.5
      +/- 47.6 Ncm (B1), 434.9 +/- 124.8 Ncm (C1), and 182.5 +/- 136.5 Ncm (D1). Two
      piece internally connected abutments exhibited higher bending moments than one
      piece internally (C1 versus D1 P = .003, A1 versus D1 P = .03) or externally (C1
      versus B1 P = .004) connected abutments. The groups with restorations did not
      show different bending moments than those without restorations. The mean bending
      moments of the restored abutments were 283.3 +/- 44.8 Ncm (A2), 291.5 +/- 31.7
      Ncm (B2), 351.5 +/- 58 Ncm (C2), and 184.3 +/- 77.7 Ncm (D2). Group C2 exhibited
      the highest bending moment (P < .05). Internally connected one-piece abutments
      (D2) were weaker than all other groups (D2 versus A2 P = .002; D2 versus B2 P =
      .001; D2 versus C2 P = .0003). CONCLUSIONS: The type of connection significantly
      influenced the strength of zirconia abutments. Superior strength was achieved by
      means of internal connection via a secondary metallic component.

PMID- 19865626
TI  - Microstructural and ultrastructural assessment of inferior alveolar nerve damage
      following nerve lateralization and implant placement: an experimental study in
      rabbits.
AB  - PURPOSE: The present study assessed damage to the inferior alveolar nerve (IAN)
      following nerve lateralization and implant placement surgery through optical and
      transmission electron microscopy (TEM). MATERIALS AND METHODS: IAN lateralization
      was performed in 16 adult female rabbits (Oryctolagus cuniculus). During the
      nerve lateralization procedure, one implant was placed through the mandibular
      canal, and the IAN was replaced in direct contact with the implant. The implant
      was placed in the right mandible, and the left side was used as a control (no
      surgical procedure). After 8 weeks, the animals were sacrificed and samples were
      prepared for optical and TEM analysis of IAN structural damage. Histomorphometric
      analysis was performed to determine the number and cross-sectional dimensions of
      nerve fascicles and myelin sheath thickness between experimental and control
      groups. The different parameters were compared by one-way analysis of variance at
      the 95% significance level. RESULTS: Alterations in the perineural and endoneural
      regions of the IAN, with higher degrees of vascularization, were observed in the
      experimental group. TEM showed that the majority of the myelinated nerve fibers
      were not affected in the experimental samples. No significant variation in the
      number of fascicles was observed, significantly larger fascicle height and width
      were observed in the control group, and significantly thicker myelin sheaths were
      observed in the experimental samples. CONCLUSION: IAN lateralization resulted in
      substantial degrees of tissue disorganization at the microstructural level
      because of the presence of edema. However, at the ultrastructural level, small
      amounts of fiber degeneration were observed.

PMID- 19865627
TI  - Influence of bone and dental implant parameters on stress distribution in the
      mandible: a finite element study.
AB  - PURPOSE: The complicated relationships between mandibular bone components and
      dental implants have attracted the attention of structural mechanics researchers
      as well as dental practitioners. Using the finite element method, the present
      study evaluated various bone and implant parameters for their influence on the
      distribution of von Mises stresses within the mandible. MATERIALS AND METHODS:
      Various parameters were considered, including Young's modulus of cancellous bone,
      which varies from 1 to 4 GPa, and that of cortical bone, which is between 7 and
      20 GPa. Implant length (7, 9, 11, 13, and 15 mm), implant diameter (3.5, 4.0,
      4.5, and 5.5 mm), and cortical bone thickness (0.3 to 2.1 mm) were also
      considered as parameters. Assumptions made in the analysis were: modeling of the
      complex material and geometric properties of the bone and implant using two
      dimensional triangular and quadrilateral plane strain elements, 50%
      osseointegration between bone and implant, and linear relationships between the
      stress value and Young's modulus of both cancellous and cortical bone at any
      specific point. RESULTS: An increase in Young's modulus and a decrease in the
      cortical bone thickness resulted in elevated stresses within both cancellous and
      cortical bone. Increases in the implant length led to greater surface contact
      between the bone and implant, thereby reducing the magnitude of stress.
      CONCLUSIONS: The applied masticatory force was demonstrated to be the most
      influential, in terms of differences between minimum and maximum stress values,
      versus all other parameters. Therefore loading should be considered of vital
      importance when planning implant placement.

PMID- 19865628
TI  - Effects of implant diameter, insertion depth, and loading angle on stress/strain
      fields in implant/jawbone systems: finite element analysis.
AB  - PURPOSE: To investigate the interactions of implant diameter, insertion depth,
      and loading angle on stress/strain fields in a three-dimensional finite element
      implant/jawbone system and to determine the influence of the loading angle on
      stress/strain fields while varying the implant diameter and insertion depth.
      MATERIALS AND METHODS: Four finite element models were created, which
      corresponded to two implant diameters and two insertion depths. The jawbone was
      composed of cortical and cancellous bone and modeled as a linearly elastic
      medium; the implant had a detailed screw structure and was modeled as an elastic
      plastic medium. Static loading was applied to the coronal surface of the implant
      with a maximum load of 200 N for all the models. Loading directions were varied,
      with buccolingually applied loading angles ranging from 0 to 85 degrees. RESULTS:
      Increases in the angle of force application caused not only increased maximum
      stress/strain values but worsened stress/strain distribution patterns in the bone
      and implant. The maximum stress in the bone always occurred at the upper edge of
      the cortical bone on the lingual side adjacent to the implant. The use of a
      larger-diameter implant or an increased insertion depth significantly reduced the
      maximum stress/strain values, improved the stress/strain distribution patterns
      and, in particular, decreased the stress/strain sensitivity to loading angle.
      CONCLUSIONS: A narrow-diameter implant, when inserted into jawbone with a shallow
      insertion depth and loaded with an oblique loading angle, is most unfavorable for
      stress distribution in both bone and implant. An optimized design of the neck
      region of an implant, in combination with a carefully controlled implant
      insertion depth that sets the threads of the implant neck well below the upper
      edge of the cortical bone, should be especially effective in improving the
      biomechanical environment for the maintenance of bone in implant/bone systems.

PMID- 19865629
TI  - Immediate rehabilitation of the edentulous maxilla: preliminary results of a
      single-cohort prospective study.
AB  - PURPOSE: This article reports preliminary results of a single-cohort prospective
      study that sought to evaluate a new surgical protocol for the immediate
      rehabilitation of edentulous maxilla without using bone grafting. MATERIALS AND
      METHODS: Twenty consecutive patients in need of a full-arch maxillary
      rehabilitation were included in the study. Each patient received four tilted
      implants that engaged the posterior and the anterior sinus wall and two axial
      implants in the anterior maxilla. A total of 120 implants (30 Branemark System MK
      IV and 90 NobelSpeedy Groovy) was inserted. Acrylic resin provisional prostheses
      were delivered within 4 hours of implant placement, and definitive restorations
      were placed 4 to 6 months later. Follow-up visits were scheduled every 6 months
      for the first 2 years and yearly thereafter. At each follow-up appointment,
      plaque and bleeding indexes were scored, periapical radiographs were obtained to
      assess marginal bone level changes, and patient satisfaction was recorded by
      means of a questionnaire. RESULTS: The follow-up ranged between 18 and 42 months
      (average, 27.2 months). No implants failed. All prostheses were stable and
      functional. No adverse events occurred. At 1 year, mean marginal bone loss around
      axial and tilted implants was similar: 0.8 mm for axial implants (SD 0.4, n = 30)
      and 0.9 mm for tilted implants (SD 0.5 mm, n = 60) (P > .05). Plaque and bleeding
      scores decreased over time, and patient satisfaction with both esthetics and
      function increased. CONCLUSIONS: This technique can be considered a viable
      treatment modality for the immediate rehabilitation of the edentulous maxilla, as
      it provides optimal support in the posterior region, minimizes distal
      cantilevers, and avoids bone grafting or sinus augmentation.

PMID- 19865630
TI  - Bone formation around immediately loaded and submerged dental implants with a
      modified sandblasted and acid-etched surface after 4 and 8 weeks: a human
      histologic and histomorphometric analysis.
AB  - PURPOSE: A high clinical and radiographic level of osseointegration has been
      reported for early and immediately loaded (IL) implants. The aim of this study
      was to analyze, histologically and histomorphometrically, the bone-titanium
      interface of IL and submerged titanium implants that were retrieved at 4 and 8
      weeks after placement. MATERIALS AND METHODS: Four patients underwent
      rehabilitation of the posterior mandible with fixed prostheses, and an additional
      implant was inserted distally in the mandible. In two patients, the additional
      implants were put into nonfunctional immediate loading with a fixed provisional
      prosthesis on the same day of the implant surgery, whereas in the other two
      patients, the implants were left submerged. The implant stability quotients at
      implant insertion were 70 and 67 for the submerged implants and 69 and 77 for the
      IL implants. Before retrieval, the IL implants were clinically osseointegrated
      and were not mobile. After 4 and 8 weeks, the four implants (two IL and two
      submerged) were retrieved with a 5-mm trephine and processed for histologic
      examination. RESULTS: After 4 weeks, the IL implant showed a bone-implant contact
      percentage (BIC) of 65.6%, while the BIC for the submerged implant was 54.7%.
      After 8 weeks, the BIC was 76.2% for the IL implant, while for the submerged
      implant it was 62.3%. CONCLUSIONS: Very high BICs were present after 4 and 8
      weeks around both submerged and IL implants, with the latter showing a higher
      quantity of bone. IL did not impede bone formation in the early healing periods.

PMID- 19865631
TI  - Clinical and histologic healing of human extraction sockets filled with calcium
      sulfate.
AB  - PURPOSE: The aim of this investigation was to evaluate whether the placement of
      medical-grade calcium sulfate hemihydrate (MGCSH) in fresh extraction sockets
      might affect the quality of newly formed bone and influence crestal bone changes.
      MATERIALS AND METHODS: Forty patients who needed maxillary single-tooth
      extraction followed by implant insertion were enrolled in the study. Alveoli were
      required to have four remaining intact walls. After tooth extraction, 22 patients
      received MGCSH in the extraction sockets (test group), and 18 received no
      grafting material (control group). At the time of extraction and 3 months later
      (at implant placement surgery), vertical and horizontal socket dimensions were
      measured. In addition, during implant placement, tissue specimens were harvested
      for histologic and immunohistochemical evaluations. Comparisons of test and
      control tissues were performed with the unpaired Student t test. RESULTS:
      Vertical resorption of the buccal socket walls and reduction of the buccopalatal
      width were more pronounced at control sites than at MGCSH sites (1.2 mm versus
      0.5 mm, and 3.2 mm versus 2.0 mm, respectively). Formation of 100% living
      trabecular bone with woven and lamellar arrangements was found in both test and
      control sections. The average trabecular bone area fraction was greater in the
      grafted specimens than in control specimens (58.8% versus 47.2%). In the test
      group, the average percentage of lamellar bone increased from 16.4% to 43.6% from
      the crestal to the apical region and was greater than in unfilled specimens
      (11.1% coronally, 22.2% apically; P < .0001). CONCLUSIONS: MGCSH seems to be
      effective in accelerating the bone healing process and minimizing alveolar ridge
      resorption in intact fresh extraction sockets.

PMID- 19865632
TI  - Effects of implant design and surface roughness on crestal bone and soft tissue
      levels in the esthetic zone.
AB  - PURPOSE: To evaluate the effects of implant geometry and collar macrostructure
      and microstructure on crestal bone height, mobility values, and attachment levels
      using two different types of radiographic analysis. MATERIALS AND METHODS:
      Subjects included in this study were those who had single-tooth implants restored
      in the maxillary esthetic zone. Bone levels were measured from the implant
      abutment (IA) interface on standardized radiographs at baseline and after 5 years
      using digital and standard methods. The digital method converted the radiographs
      into three-dimensional models based on radiodensity so that bone levels could be
      measured. Clinical attachment levels and Periotest values were recorded and all
      data were analyzed statistically. RESULTS: The bone position from the IA
      interface for the rough-collar implant group was a mean of -0.61 +/- 0.08 mm and
      it was -1.55 +/- 0.10 mm for the smooth-collar implant group (-1.96 +/- 0.16 mm
      for implants with a stepped collar and -0.85 +/- 0.19 mm for implants with a
      straight collar). The mean bone level change over the 5-year period for the rough
      implants was -0.19 +/- 0.09 mm and it was -0.36 +/- 0.06 mm for the smooth
      implants. The crestal bone position relative to the implant at the time of
      surgery influenced mean bone level changes significantly. There were
      statistically significant differences in clinical attachment levels depending on
      implant location and on implant group and length. CONCLUSIONS: Implants with
      straight collars had less bone loss at the 5-year interval than implants with
      stepped collars. Bone level changes were greater when the implant was placed
      further subcrestal. The digitally converted radiographic method was significantly
      more precise for evaluating changes in bone levels. These findings suggest that
      implant geometry and implant surface roughness may play a significant role in
      bone level changes in the esthetic zone.

PMID- 19865633
TI  - Radiographic evaluation of marginal bone levels around platform-switched and non
      platform-switched implants used in an immediate loading protocol.
AB  - PURPOSE: The aim of this clinical study was to assess the marginal bone around
      two different types of implant-abutment junctions-a so-called platform-switched
      assembly and a conventional external-hexagon connection-after 24 months.
      MATERIALS AND METHODS: Forty-five patients were included in this prospective
      study. All selected patients required the extraction of one or two hopeless teeth
      in maxillary and mandibular region monoradicular and second premolar teeth, and
      were randomly assigned to one of two groups. The first group received 34 implants
      with an external-hexagon junction with the abutment and the second group received
      30 implants with platform-switched abutments. Implants were positioned
      immediately after tooth extraction and were loaded immediately. RESULTS: After 24
      months, a cumulative survival rate of 100% was reported for all implants. The
      platform-switching group showed a mean bone loss of 0.78 +/- 0.49 mm and the
      external-hexagon group showed a mean bone loss of 0.73 +/- 0.52 mm (no
      statistically significant difference between groups). CONCLUSION: The results of
      this study indicate that implants placed immediately in fresh extraction sockets
      and loaded immediately represent a predictable procedure, with no differences in
      bone level changes between "platform-switched" and conventional external-hexagon
      implants after 24 months.

PMID- 19865634
TI  - Outcomes assessment of patients treated with osseointegrated dental implants at
      the University of Washington Graduate Prosthodontic Program, 1988 to 2000.
AB  - PURPOSE: The purpose of this retrospective study was to review and assess the
      outcomes of subjects treated with dental implants at the University of Washington
      Graduate Prosthodontic Program from 1988 to 2000. MATERIALS AND METHODS: A
      retrospective review and an outcomes assessment were conducted of patients
      treated with osseointegrated implants between 1988 and 2000 at the University of
      Washington Graduate Prosthodontic Program. Patients were treated by graduate
      students. All included patients had a prosthesis that had been in service for at
      least 5 years. Implants and prostheses were assessed by chart review, phone
      survey, and clinical review. Clinical review consisted of mobility testing, soft
      tissue evaluation, and occlusal evaluation. Specific success criteria were used
      and life table analyses of implants and prostheses were performed. RESULTS: Of a
      total of 114 patients treated, 69 subjects (60.5% of those treated) participated
      in the assessment; 103 prostheses supported by 273 implants were reviewed
      clinically. The estimated cumulative survival rate was 96.3% for all implants and
      85.4% for all prostheses. CONCLUSIONS: A retrospective review of 69 subjects who
      were treated in the University of Washington Graduate Prosthodontic Program
      between the years 1988 and 2000 showed an implant survival rate of 96.3% and a
      prosthesis survival rate of 85.4%. Prostheses showed higher failure rates than
      implants.

PMID- 19865635
TI  - The nasopalatine canal as an anatomic buttress for implant placement in the
      severely atrophic maxilla: a pilot study.
AB  - PURPOSE: The aim of this study was to present an alternative treatment concept
      for the rehabilitation of the atrophic maxilla that used the nasopalatine canal
      as an anatomic buttress for dental implant insertion and to assess patient
      satisfaction with this treatment. MATERIALS AND METHODS: The inclusion criterion
      for the study consisted of the presence of severe resorption of the edentulous
      maxilla (Class V according to the Cawood and Howell classification). In each
      patient, one implant was positioned in the nasopalatine canal. Additional
      implants were also placed in the remaining maxillary bone. The patients were
      followed for a minimum of 2 years after prosthesis connection. Satisfaction with
      the prosthesis was evaluated after 12 months using a visual analog scale.
      RESULTS: Seven patients with severely resorbed edentulous maxillae received a
      total of seven implants in the nasopalatine buttress and 29 implants posterior to
      this structure. One of the seven implants in the nasopalatine canal was lost
      during the osseointegration phase. All patients had stable prostheses at the end
      of the observation period. Patients were satisfied with comfort and stability,
      ability to speak, ease of cleaning, and esthetics and function of the prosthesis.
      Five patients experienced minor sensory alterations during the first weeks after
      surgery. At the final examination, which took place after a mean of 5 years
      (range, 3 to 7 years), all patients expressed the presence of normal sensation.
      CONCLUSIONS: It appears that implants in the nasopalatine canal may be a viable
      treatment approach for the rehabilitation of the severely atrophied maxilla.
      Patients were satisfied with a prosthesis supported by implants in the
      nasopalatine canal.

PMID- 19865636
TI  - Computed tomography-based planning and three-dimensional modeling for
      craniofacial implant placement: a technical note.
AB  - Facial defects can result from trauma, treatment of neoplasms, or congenital
      malformations, and their restoration is still a challenge for both surgeon and
      prosthodontists. Craniofacial implants can provide many benefits for prosthetic
      rehabilitation of facial defects; however, accurate placement of extraoral
      implants is vital for clinical success. Three-dimensional modeling is a novel
      technique that not only helps the surgeon to evaluate potential bone sites and
      adjacent structures, but also facilitates planning of the extraoral implant
      treatment by the prosthodontist. This technical report describes the use of three
      dimensional modeling and planning for craniofacial implant placement.

PMID- 19865637
TI  - A modified transantral endoscopic technique for the removal of a displaced dental
      implant from the maxillary sinus followed by simultaneous sinus grafting.
AB  - The efficacy of transantral endoscopy for the removal of a foreign material from
      the maxillary sinus has been reported previously. Endoscopy has also been used
      for removal of dental implants after their displacement into the maxillary sinus
      either during implant placement or subsequently, during implant integration or
      loading. This case report describes the removal of a dental implant from the
      maxillary sinus using a modified transantral endoscopic approach combined with
      simultaneous grafting of the sinus cavity.

PMID- 19865641
TI  - Animal silks: their structures, properties and artificial production.
AB  - This feature article reviews recent progress in the understanding of the
      hierarchically organized structures, the perfectly balanced mechanical properties
      and the structure-property relationship of the natural animal silk fibres, as
      well as the experimental attempts to fabricate man-made silk fibres by means of
      wet spinning, dry spinning, electrospinning and transgenosis.

PMID- 19865642
TI  - The long-overlooked enzymology of a nonribosomal peptide synthetase-independent
      pathway for virulence-conferring siderophore biosynthesis.
AB  - Siderophores are high-affinity ferric iron chelators biosynthesised and excreted
      by most microorganisms that play an important role in iron acquisition.
      Siderophore-mediated scavenging of ferric iron from hosts contributes
      significantly to the virulence of pathogenic microbes. As a consequence
      siderophore biosynthesis is an attractive target for chemotherapeutic
      intervention. Two main pathways for siderophore biosynthesis exist in microbes.
      One pathway involves nonribosomal peptide synthetase (NRPS) multienzymes while
      the other is NRPS-independent. The enzymology of NRPS-mediated siderophore
      biosynthesis has been extensively studied for more than a decade. In contrast,
      the enzymology of NRPS-independent siderophore (NIS) biosynthesis was overlooked
      for almost thirty years since the first genetic characterisation of the NIS
      biosynthetic pathway to aerobactin. However, the past three years have witnessed
      an explosion of interest in the enzymology of NIS synthetases, the key enzymes in
      the assembly of siderophores via the NIS pathway. The biochemical
      characterisation of ten purified recombinant synthetases has been reported since
      2007, along with the first structural characterisation of a synthetase by X-ray
      crystallography in 2009. In this feature article we summarise the recent progress
      that has been made in understanding the long-overlooked enzymology of NRPS
      independent siderophore biosynthesis, highlight important remaining questions,
      and suggest likely directions for future research.

PMID- 19865643
TI  - Site-selective scission of human genome by artificial restriction DNA cutter.
AB  - By using an artificial restriction DNA cutter which is composed of Ce(iv)/EDTA
      and two pseudo-complementary peptide nucleic acid strands (pcPNAs), only one
      target site in the whole genome of human beings (one site in the X chromosome)
      was selectively hydrolyzed.

PMID- 19865645
TI  - High-throughput confinement and detection of single DNA molecules in aqueous
      microdroplets.
AB  - A droplet-based microfluidic system combined with high-sensitivity optical
      detection is used as a tool for high-throughput confinement and detection of
      single DNA molecules.

PMID- 19865644
TI  - Homologous recombination in human cells using artificial restriction DNA cutter.
AB  - The double strand break induced by an artificial restriction DNA cutter (ARCUT)
      was successfully repaired in human cells with high frequencies through homologous
      recombination.

PMID- 19865646
TI  - In situ oxidation synthesis of Ag/AgCl core-shell nanowires and their
      photocatalytic properties.
AB  - Ag/AgCl core-shell nanowires with uniform structure have been synthesized in
      large quantities via an in situ oxidation reaction between pentagonal Ag
      nanowires and FeCl(3) solution at room temperature, which exhibit excellent
      photocatalytic performance for decomposition of methylene orange under visible
      light irradiation.

PMID- 19865647
TI  - An asymmetric organocatalytic approach towards allylic amines and beta-keto amino
      compounds.
AB  - The enantioselective organocatalysed addition of beta-keto benzothiazolesulfones
      to N-Boc-protected imines, leading to intermediates easily transformed into
      optically active allylic amines or beta-keto amino compounds, is presented.

PMID- 19865648
TI  - Carbohydrate sensing using a fluorescent molecular tweezer.
AB  - A fluorescent molecular tweezer for carbohydrates has been prepared which
      utilises two boronic acid receptor groups.

PMID- 19865649
TI  - Bio-reversible polyPEGylation.
AB  - Protein conjugation with biodegradable polyPEGMA and subsequent release is
      described.

PMID- 19865651
TI  - Photochemical fabrication of hierarchical Ag nanoparticle arrays from domain
      selective Ag(+)-loading on block copolymer templates.
AB  - Well-ordered Ag nanoparticle arrays with high particle density were fabricated by
      photochemical reduction of domain-selective Ag(+)-loading on hydrophobic
      polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) self-assembled diblock
      copolymer templates.

PMID- 19865650
TI  - SERRS fiber probe: fabrication of silver nanoparticles at the aperture of an
      optical fiber used for SNOM.
AB  - At the aperture of an optical fiber coupled with a SNOM SERRS-active Ag
      nanoparticles were selectively fabricated in a mixture of AgNO(3) and sodium
      citrate aqueous solution by photo-reduction due to an evanescent field.

PMID- 19865652
TI  - Skeletal rearrangement of all-carbon spiro skeletons mediated by a Lewis acid.
AB  - Mediated by AlCl(3), substituted spiro[4.5]deca-tetraenes underwent novel and
      selective skeletal rearrangement to generate indene derivatives in high to
      excellent yields.

PMID- 19865653
TI  - Nitrile insertion into a boryl-substituted five-membered zirconacycloallenoid:
      unexpected formation of a zwitterionic boratirane product.
AB  - Nitrile insertion into a zirconacycloallenoid complex leads to the formation of a
      seven-membered ring product with an attached boratirane unit.

PMID- 19865654
TI  - Original use of the same heterogeneous chiral catalyst batch to promote different
      asymmetric reactions.
AB  - An electrogenerated heterogeneous chiral (poly)salen-thiophene chromium complex
      successfully promoted different asymmetric catalytic reactions in an original
      successive manner, demonstrating its high stability and versatility.

PMID- 19865655
TI  - Catalytic enantioselective boron conjugate addition to cyclic carbonyl compounds:
      a new approach to cyclic beta-hydroxy carbonyls.
AB  - The highly enantioselective conjugate boration of six-membered and seven-membered
      cyclic enones and unsaturated esters was achieved by the use of a copper-(R,S)
      Taniaphos complex with up to 99% ee under optimal conditions.

PMID- 19865656
TI  - Efficient ruthenium-catalyzed synthesis of [3]dendralenes from 1,3-dienic allylic
      carbonates.
AB  - Selective elimination from 1,3-dienic allylic carbonates occurs in the presence
      of a catalytic amount of [Ru(C(5)Me(5))(4,4'-di-Bu(t)-2,2'
      bipyridine)(CH(3)CN)]PF(6) and provides efficient access to a variety of
      [3]dendralenes.

PMID- 19865657
TI  - Bromomaleimides: new reagents for the selective and reversible modification of
      cysteine.
AB  - Bromomaleimides react rapidly and selectively with cysteine to afford
      thiomaleimides which can be cleaved with a phosphine to regenerate the cysteine
      or treated with a base to afford dehydroalanine.

PMID- 19865658
TI  - DNA templated nucleophilic aromatic substitution reactions for fluorogenic
      sensing of oligonucleotides.
AB  - We have developed an S(N)Ar reaction-triggered fluorescence probe using a new
      fluorogenic compound derivatized from 7-aminocoumarin for oligonucleotides
      detection.

PMID- 19865659
TI  - Facile synthesis of Nafion-stabilized iridium nanoparticles and their direct use
      for fuel cells and water electrolyzers.
AB  - Using a quite small but suitable amount of Nafion as stabilizer, iridium colloids
      with well controlled particle size were synthesized and directly used for fuel
      cells or water electrolyzers without further removal or addition of Nafion,
      meanwhile, a strategy for fabrication of supported catalyst with high utilization
      was also proposed.

PMID- 19865660
TI  - First symmetrical banana compounds exhibiting SmAP(R) mesophase and unique
      transition between two orthogonal polar phases.
AB  - Novel banana-shaped liquid crystals with stilbene bridges were synthesized. All
      presented materials exhibit the polarization-randomized non-tilted smectic phase
      (SmAP(R)) in a broad temperature range and the antiferroelectric non-tilted
      smectic phase (SmAP(A)) at room temperature.

PMID- 19865661
TI  - Multi-responsive amphiphilic gold nanoparticles (AuNPs) protected by poly(ether
      amine) (PEA).
AB  - Multi-responsive amphiphilic gold nanoparticles (AuNPs) protected by graft
      poly(ether amine) have been prepared simply by a one-pot photochemical synthesis
      in the presence of thio-graft poly(ether amine) (gPEA-SH) and the mechanism was
      studied in detail.

PMID- 19865662
TI  - Intermolecular aurophilic interactions facilitate assembly of a complex rotaxane
      in solution.
AB  - We describe the formation of a complex [2]rotaxane both in solution and in the
      solid state. The rotaxane ring is composed of a cyclic trinuclear gold complex
      and the Au(PMe(3))(2)(+) rod is held in place by three aurophilic interactions to
      the ring Au atoms. The existence of the [2]rotaxane in solution is confirmed by
      VT-NMR and MS analysis.

PMID- 19865663
TI  - A facile method to clickable sensing polymeric nanoparticles.
AB  - Clickable biocompatible nanoparticles were prepared in a one-pot process by
      microemulsion polymerization using acrylamide, N,N'-methylene bisacrylamide and
      either N-(11-azido-3,6,9-trioxaundecanyl)acrylamide or N-propargylacrylamide,
      which were then readily modified by CuAAC reaction to afford sensing
      nanomaterials.

PMID- 19865664
TI  - Iridium-catalyzed regio- and enantioselective allylic alkylation of
      fluorobis(phenylsulfonyl)methane.
AB  - Highly regio- and enantioselective allylic alkylation of
      fluorobis(phenylsulfonyl)methane (FBSM) has been realized by
      [Ir(COD)Cl](2)/phosphoramidite, affording enantiopure
      fluorobis(phenylsulfonyl)methylated compounds bearing a terminal alkene, which
      could be converted to monofluoro-methylated ibuprofen in just two steps without
      loss of the optical purity (95% ee).

PMID- 19865666
TI  - A new route to high yield sugars from biomass: phosphoric-sulfuric acid.
AB  - We have developed a simple and effective route for the high yield extraction of
      sugars from cellulosic based biomass. This process uses a combination of a
      cellulose decrystallization step with a mixture of phosphoric and sulfuric acid,
      followed by a hydrolysis step producing sugars (xylose and glucose) with yields
      of approximately 90%.

PMID- 19865667
TI  - Single-phase aqueous approach toward Pd sub-10 nm nanocubes and Pd-Pt
      heterostructured ultrathin nanowires.
AB  - Monodisperse, highly-selective sub-10 nm Pd and Rh nanocubes have been
      successfully synthesized and, for the first time, bimetallic Pd-Pt
      heterostructured ultrathin nanowires have been achieved through using Pd
      nanocubes as seeds by a one-pot, single-phase aqueous method.

PMID- 19865665
TI  - Mesoporous zirconium oxide nanomaterials effectively enrich phosphopeptides for
      mass spectrometry-based phosphoproteomics.
AB  - This work represents the first use of mesoporous zirconium oxide nanomaterials
      for highly effective and selective enrichment of phosphorylated peptides.

PMID- 19865668
TI  - Colour modification action of an upconversion photonic crystal.
AB  - Colour modification of the upconversion emission has been successfully achieved
      in a novel upconversion photonic crystal.

PMID- 19865669
TI  - Highly sensitive and selective detection of silver ions and silver nanoparticles
      in aqueous solution using an oligonucleotide-based fluorogenic probe.
AB  - We developed a new homogeneous assay-using SYBR Green I and repeats of 20 C
      nucleotides-for the highly selective and sensitive detection of silver ions and
      silver nanoparticles.

PMID- 19865670
TI  - Photocontrolled nucleobase binding to an organometallic Ru(II) arene complex.
AB  - The complex [(p-cym)Ru(bpm)(py)][PF(6)](2) (where p-cym = para-cymene, bpm = 2,2'
      bipyrimidine and py = pyridine) is the first ruthenium(ii) arene complex that can
      selectively photodissociate a monodentate ligand (py) when excited with visible
      light and form a reactive aqua derivative able to bind to a DNA base.

PMID- 19865671
TI  - Host-guest transformational correlations for a gas inclusion co-crystal on
      changing gas pressure and temperature.
AB  - The CO(2) adsorption behavior and inclusion structure of a flexible single
      crystal host [Cu(2)(bza)(4)(pyz)](n) were studied under various conditions (203
      373 K, <15.4 MPa) and the correlation between changes in gas adsorption behavior
      and the structures of guest arrangement and host component packing were
      investigated.

PMID- 19865672
TI  - Ionothermal synthesis of hexagonal-phase NaYF(4):Yb(3+),Er(3+)/Tm(3+)
      upconversion nanophosphors.
AB  - Water-soluble pure hexagonal-phase NaYF(4):Yb(3+),Er(3+)/Tm(3+) nanoparticles
      were obtained by an ionothermal method for the first time which offers a new
      alternative in synthesizing such materials.

PMID- 19865673
TI  - BN tubular layer-sheathed CaS:Eu(2+) nanowires as stable red-light-emitting
      nanophosphors.
AB  - Novel chemically stable CaS:Eu(2+) nanowires protected by BN tubular sheaths were
      synthesized via a one-step and catalyst-free method for the first time; the
      nanostructures showed a red-light emission when excited by approximately 450 nm
      blue light.

PMID- 19865674
TI  - Reverse vesicles formed by hydrogen bonded arylamide-derived triammonium
      cyclophanes and hexaammonium capsule.
AB  - Hydrogen bonded rigid imine-based macrocycles and capsules have been reduced to
      cyclic triamines and two-layered hexaamines, the triammonium and hexaammonium
      derivatives of which are revealed to form reverse vesicles in organic liquids of
      low polarity, which are characterized by SEM, AFM, (HR)TEM, DLS and XRD.

PMID- 19865675
TI  - The regioselective photochemical rearrangement of alpha-[PN(t)Bu](4).
AB  - The photochemical dyotropic (two-bond shift) rearrangement of the phosphazane
      cage alpha-[PN(t)Bu](4) (alpha) into the isomer beta-[PN(t)Bu](4) (beta) occurs
      via a multi-step radical mechanism; the structures of the alpha and beta isomers
      are directly analogous to isovalent alpha- and beta-As(4)S(4) and P(4)S(4).

PMID- 19865676
TI  - Detection of DNA using bioactive paper strips.
AB  - Paper strips containing DNA-conjugated microgels (MG) are used to achieve
      sensitive DNA detection in three steps: target DNA promoted ligation of a DNA
      primer to the MG-bound DNA, rolling circle amplification (RCA) between the primer
      and a circle DNA, and hybridization of the RCA products and a fluorescent DNA
      probe.

PMID- 19865677
TI  - A tetranuclear iridium(iii) complex with a flavin analogue as a bridging ligand
      in different coordination modes and exchangeable anion encapsulation in a
      supramolecular cage.
AB  - A novel tetranuclear Ir(iii) complex involving unprecedented coordination modes
      of alloxazine formed a closed pi-space by intermolecular hydrogen bonding and the
      counter anions encapsulated in the space could be exchanged via self-assembly.

PMID- 19865678
TI  - Effect of chirality of L/D-proline and prochiral glycine as the linker amino acid
      in five-atom linked thymidinyl-(alpha-amino acid)-thymidine dimers.
AB  - The chirality of the amide linker in dimer blocks was found to have a profound
      effect on the orientation of base stacking interactions as studied by CD and NMR
      spectroscopy.

PMID- 19865679
TI  - Europium complexes with high total photoluminescence quantum yields in solution
      and in PMMA.
AB  - We have prepared complexes of formula [Eu(beta-diketonate)(3)(DPEPO)] and shown
      quantitative excited-state energy transfer from the ligands combined with
      efficient Ln luminescence leading to exceptionally-high total photoluminescence
      quantum yield of up to 80% in solution and in PMMA.

PMID- 19865680
TI  - Dynamic kinetic resolution in the asymmetric synthesis of atropisomeric biaryl[4]
      and [5]helicene quinones.
AB  - Total control of axial and helical chirality elements of a (2-biphenyl)
      substituted tetrahydro[5]helicene quinone and the configurationally stable
      dihydro[4]helicene analogue was achieved in a dynamic kinetic resolution process
      of an axially chiral racemic diene promoted by an enantiopure sulfinyl
      benzoquinone.

PMID- 19865681
TI  - m-Terphenyl-modified carbazole host material for highly efficient blue and green
      PHOLEDS.
AB  - A simple m-terphenyl modified carbazole derivative, 9-phenyl-3,6-bis
      [1,1';3'1'']terphenyl-5'-yl-9H-carbazole (CzTP) was developed. By using CzTP as a
      host material, the PHOLEDs showed the maximum power efficiencies (eta(p, max)) of
      55 lm W(-1) for blue and 113 lm W(-1) for green, respectively.

PMID- 19865682
TI  - A generic route to fluoroalkyl-containing phosphanes.
AB  - The reaction of trimethylsilyl-containing phosphanes with perfluoroiodoalkanes
      provides a general and convenient route to perfluoroalkyl-containing phosphanes.

PMID- 19865683
TI  - In situ preparation of network forming gold nanoparticles in agarose hydrogels.
AB  - Gold nanoparticles are obtained by reduction of a Au(iii) precursor within an
      agarose hydrogel where they form percolating networks upon partial dehydration
      and shrinkage of the gel.

PMID- 19865684
TI  - Synthesis of superparamagnetic iron(III) oxide nanowires in double-walled carbon
      nanotubes.
AB  - The synthesis and characterization of superparamagnetic iron(iii) oxide nanowires
      confined within double-walled carbon nanotubes by capillary filling with a melted
      precursor (iron iodide) followed by thermal treatment is reported for the first
      time.

PMID- 19865689
TI  - 1,3-Dipolar cycloadditions: applications to the synthesis of antiviral agents.
AB  - In the present perspective the advances and real possibilities of 1,3-dipolar
      cycloadditions as key steps in the total synthesis of virus inhibitors are
      described. Azides, nitrones, and azomethine ylides are the most appropriate 1,3
      dipoles for the synthesis of privileged structures with the highest biological
      responses against viruses.

PMID- 19865691
TI  - Olefin metathesis in carotenoid synthesis.
AB  - Olefin metathesis is a powerful and widely applicable synthetic method for carbon
      carbon double bond formation. However, its application to the synthesis of
      conjugating polyene chains has been very limited because of possible undesired
      side reactions. We attempted to apply this method to the synthesis of symmetrical
      carotenoids. In this paper, the syntheses of violaxanthin and mimulaxanthin are
      described using the olefin metathesis protocol.

PMID- 19865690
TI  - Efficient synthesis of the C(7)-C(20) subunit of amphidinolides C and F.
AB  - Synthesis of the C(7)-C(20) subunit of amphidinolides C and F has been
      accomplished utilizing a Me(3)Al-mediated ring opening of a vinyl iodide/allylic
      epoxide to establish the C(12,13)anti stereochemistry, an organolithium
      coupling/olefination sequence to construct the C(9)-C(11) diene moiety and a
      sulfone alkylation/hydroxylation strategy to join the C(7)-C(14) and C(15)-C(20)
      fragments.

PMID- 19865692
TI  - Fluorescent detection of methylmercury by desulfurization reaction of rhodamine
      hydrazide derivatives.
AB  - Exposure to methylmercury causes severe damage to various tissues and organs in
      humans. Although a variety of fluorescent chemosensors have been exploited, only
      few biological monitoring systems for organomercury species have been described
      to date. In this report, we describe an irreversible rhodamine chemosensor for
      the detection of methylmercury and real-time monitoring of methylmercury in
      living cells and organisms.

PMID- 19865693
TI  - Synthesis of acetal protected building blocks using flow chemistry with flow I.R.
      analysis: preparation of butane-2,3-diacetal tartrates.
AB  - The syntheses of butane-2,3-diacetal protected tartrate derivatives are described
      using continuous flow processing techniques with in-line purification and I.R.
      analytical protocols.

PMID- 19865694
TI  - Sensing of peptide hormones with dynamic combinatorial libraries of metal-dye
      complexes: the advantage of time-resolved measurements.
AB  - A dynamic combinatorial library of metal-dye complexes was obtained by reacting
      aqueous solutions of the dyes Methyl Calcein Blue, Arsenazo I, and Xylenol Orange
      with CuCl(2) and NiCl(2). The mixture gave a characteristic UV-Vis response upon
      addition of the peptide hormones angiotensin I and angiotensin II. This allowed
      distinguishing pure samples of peptide hormones from mixtures. The discriminatory
      power of the sensor was enhanced when the several UV/Vis measurements were
      performed during the equilibration process of the library.

PMID- 19865695
TI  - Biocatalytic oxidation by chloroperoxidase from Caldariomyces fumago in
      polymersome nanoreactors.
AB  - The encapsulation of chloroperoxidase from Caldariomyces fumago (CPO) in block
      copolymer polymersomes is reported. Fluorescence and electron microscopy show
      that when the encapsulating conditions favour self-assembly of the block
      copolymer, the enzyme is incorporated with concentrations that are 50 times
      higher than the enzyme concentration before encapsulation. The oxidation of two
      substrates by the encapsulated enzyme was studied: i) pyrogallol, a common
      substrate used to assay CPO enzymatic activity and ii) thioanisole, of which the
      product, (R)-methyl phenyl sulfoxide, is an important pharmaceutical
      intermediate. The CPO-loaded polymersomes showed distinct reactivity towards
      these substrates. While the oxidation of pyrogallol was limited by diffusion of
      the substrate into the polymersome, the rate-limiting step for the oxidation of
      thioansiole was the turnover by the enzyme.

PMID- 19865696
TI  - Magnesium-mediated intramolecular reductive coupling: a stereoselective synthesis
      of C(2)-symmetric 3,4-bis-silyl-substituted adipic acid derivatives.
AB  - Chiral C(2)-symmetric 3,4-bis-silyl-substituted adipic acid derivatives have been
      synthesised by a Mg/trimethylsilyl chloride-mediated intramolecular reductive
      coupling of symmetrical disiloxanes of beta-silylacrylic acid N-oxazolidinone
      derivatives. Efficient and short syntheses of enantiomerically pure enantiomers
      of 2,6-dioxabicyclo[3.3.0]octane-3,7-dione have been achieved from the bis
      silylated adipic acid derivatives using Fleming-Tamao oxidation as the key step.

PMID- 19865698
TI  - pi Complexes in benzidine rearrangement.
AB  - By the use of DFT calculations, the title rearrangement, Ph-NH-NH-Ph () --> H(2)N
      C(6)H(4)-C(6)H(4)-NH(2) (2), was studied for the first time. Although it is a
      classical reaction (found in 1862), its mechanism is almost entirely unknown.
      There are three complexities associated with this mechanism. The first is the
      various rate orders for substituted hydrazobenzenes. The second is the product
      distribution. The third is the result of the kinetic isotope effect which is
      difficult to interpret. A reaction model, , (H(3)O(+))(2) and (H(2)O)(10) was
      used to trace the reaction path. Two hydronium ions were included, because there
      are two nitrogen atoms in . In the paths of the main reaction, (H(+))(2)-->H(+) +
      H(+), transient intermediates were found. Through their conversion, the second
      product, diphenyline (), was reached. For H(+), only the Claisen shift path was
      found, and the pi complex proposed by Dewar was not found. The absence is in
      accord with the kinetic result of Hammond and Shine. But the complex was revealed
      in the dimethoxyhydrazobenzene. Thus, while Dewar's pi complex was ruled out in
      1950, it has been revived by the present calculations.

PMID- 19865697
TI  - Design of a beta-hairpin peptide-intercalator conjugate for simultaneous
      recognition of single stranded and double stranded regions of RNA.
AB  - Designing receptors that bind RNA is a challenging endeavor because of the unique
      and sometimes complex structure of RNA. However these structural features provide
      regions for ligands to bind using different types of interactions. To increase
      specificity and binding affinity to RNA, divalent systems have been designed
      which incorporate more than one binding motif into one molecule. Using this
      approach, we have designed a two part heteroconjugate, WKWK-Int, which contains a
      beta-hairpin peptide covalently linked to an RNA intercalator. This
      heteroconjugate was designed to bind duplex RNA through intercalation and
      simultaneously interact with a single stranded bulge region using the side chains
      of the beta-hairpin peptide. We have used fluorescence anisotropy experiments to
      show that the heteroconjugate has an increased binding affinity over either one
      of the individual ligands. Additionally, RNase footprinting experiments show that
      the structure of the peptide is necessary for the protection of one particular
      base in the RNA bulge region. When tested against other RNA molecules containing
      a stem-bulge structure, the designed heteroconjugate was found to be specific for
      this RNA sequence. This work provides evidence that the covalent linkage of two
      weak RNA ligands can greatly increase the binding affinity and also provide
      specificity to the binding event.

PMID- 19865699
TI  - Synthesis of functionalized H-pyrazolo[5,1-a]isoquinolines via sequential
      reactions of N'-(2-alkynylbenzylidene)hydrazides.
AB  - Diversity-oriented synthesis of functionalized H-pyrazolo[5,1-a]isoquinolines via
      sequential reactions of N'-(2-alkynylbenzylidene)hydrazide is described. Bromine
      mediated electrophilic cyclization, Ag-catalyzed alkyne nucleophilic addition,
      and palladium-catalyzed cross-coupling reaction were involved in the
      transformation.

PMID- 19865700
TI  - Ionic liquid: an efficient and recyclable medium for synthesis of unsymmetrical
      diorganyl selenides promoted by InI.
AB  - In an environmentally friendly protocol, InI was used as a reducing agent for the
      Se-Se bond to prepare unsymmetrical diorganyl selenides with very short reaction
      times, mild conditions and excellent yields using (bmim)BF(4) as a recyclable
      solvent.

PMID- 19865701
TI  - Conjugation of substituted naphthalimides to polyamines as cytotoxic agents
      targeting the Akt/mTOR signal pathway.
AB  - Though several naphthalimide derivatives have exhibited antitumor activity in
      clinical trials, some issues such as toxicity prompted further structural
      modifications on the naphthalimide backbone. A series of naphthalimides
      conjugated with polyamines were synthesized to harness the polyamine transporter
      (PAT) for drug delivery, which was beneficial for the tumor cell selectivity.
      Bioevaluation in human hepatoma HepG2 cells treated with alpha
      difluoromethylornithine (DFMO) or spermidine (Spd), human hepatoma Bel-7402 and
      normal QSG-7701 hepatocyte confirmed the PAT recognition and cell selectivity. In
      addition, the novel naphthalimide polyamine conjugate kills cells via apoptosis,
      and the Akt/mTOR signal pathway was first identified as the upstream cellular
      target through the apoptotic mechanism research. The presence of DFMO or Spd only
      either elevated or attenuated the cell apoptosis, but did not change the signal
      pathway. Collectively, the proper polyamine recognition element (i.e.,
      homospermidine) mediated effective drug delivery via the PAT, and helped the
      proper cytotoxic goods (i.e., diverse naphthalimides) exert antitumor properties.

PMID- 19865702
TI  - Selective recognition of tetrahedral dianions by a hexaaza cryptand receptor.
AB  - A hexaamine cage was synthesised in good yield by a [2+3] Schiff-base
      condensation followed by sodium borohydride reduction to be used as a receptor
      for the selective binding of anionic species. The protonation constants of the
      receptor, as well as its association constants with Cl(-), I(-), NO(3)(-), AcO(
      ), ClO(4)(-), H(2)PO(4)(-), SO(4)(2-), SeO(4)(2-) and S(2)O(3)(2-) were
      determined by potentiometry at 298.2 +/- 0.1 K in H(2)O-MeOH (50 : 50 v/v) and at
      ionic strength 0.10 +/- 0.01 mol dm(-3) in KTsO. These studies revealed a
      remarkable selectivity for dianionic tetrahedral anions by the protonated
      receptor, with association constants ranging 5.03-5.30 log units for the
      dianionic species and 1.49-2.97 log units for monoanionic ones. Single crystal X
      ray determination of [(H(6)xyl)(SO(4))(H(2)O)(6)](SO(4))(2).9.5H(2)O showed that
      one sulfate anion is encapsulated into the receptor cage sited between the two
      2,4,6-triethylbenzene caps establishing three N-HO hydrogen bonds with two
      adjacent N-H binding sites and additional O-HO hydrogen bonding interactions with
      six water of crystallization molecules. Four water molecules of the
      (SO(4))(H(2)O)(6) cluster interact with [H(6)xyl](6+) through N-HO hydrogen
      bonds. Molecular dynamics simulations (MD) carried out with SO(4)(2-) and Cl(-)
      anions in H(2)O-MeOH (50 : 50 v/v) allowed the full understanding of anion
      molecular recognition, the selectivity of the protonated receptor for SO(4)(2-)
      and the role played by the methanol and water solvent molecules.

PMID- 19865703
TI  - Ni and Pd mediate asymmetric organoboron synthesis with ester functionality at
      the beta-position.
AB  - Catalytic systems based on Ni and Pd complexes modified with chiral P-P ligands
      can be used in a convenient strategy for enantioselectively adding a boron unit
      to the beta-position of alpha,beta-unsaturated esters.

PMID- 19865704
TI  - Cation localization and movement within DNA thrombin binding aptamer in solution.
AB  - The thrombin binding aptamer, 15-mer oligonucleotide
      d[G(2)T(2)G(2)TGTG(2)T(2)G(2)], was folded into the well known antiparallel
      unimolecular G-quadruplex in the presence of (15)NH(4)(+) ions. Although the
      formed G-quadruplex is thermodynamically less stable than in the presence of K(+)
      ions, the loop conformations and folding topology are the same. On the other
      hand, titration of Na(+) ions into an aqueous solution of TBA resulted in the
      formation of one major and several minor species of G-quadruplexes. Solution
      state NMR was used to localize (15)NH(4)(+) ions between the two G-quartets
      within the core of the structure, and to determine the equilibrium binding
      constant, which equals 190 M(-1). No other potential cation binding sites were
      resolved on the time-scale of NMR spectrometer. Exchange of (15)NH(4)(+) ions
      between the inner binding site and bulk solution is characterized by the exchange
      rate constant of 1.0 s(-1) at 15 degrees C. T4 and T13 form a noncanonical base
      pair, which greatly affects access of bulk ions into the cation binding site in
      the G-quadruplex core. G2 and G11 exhibit out of plane bending towards the two TT
      loops away from the bound (15)NH(4)(+) ions, which in turn exposes them to more
      efficient chemical exchange processes with bulk ions and water.

PMID- 19865705
TI  - CCMV capsid formation induced by a functional negatively charged polymer.
AB  - A functional negatively charged polyelectrolyte, polyferrocenylsilane (PFS) was
      encapsulated in cowpea chlorotic mottle virus (CCMV) capsid proteins, yielding
      monodisperse particles of 18 nm in size with altered redox properties compared to
      the parent materials.

PMID- 19865706
TI  - Development of highly sensitive and selective molecules for detection of
      spermidine and spermine.
AB  - To establish an effective and concise procedure for determining the
      concentrations of spermidine and spermine, several functional molecules based on
      phenolphthalein and two crown loops were constructed. Host 5 with a dimethylamino
      group showed excellent selectivity for spermidine and spermine among other
      biogenic amines and high sensitivity compared with basic host 1.

PMID- 19865707
TI  - Synthesis, photolysis studies and in vitro photorelease of caged TRPV1 agonists
      and antagonists.
AB  - The synthesis of a range of caged TRPV1 agonists and antagonists is reported. The
      photolysis characteristics of these compounds, when irradiated with a 355 nm
      laser, have been studied and in all cases the desired compound was produced.
      Photolysis of a caged TRPV1 agonist in cultured trigeminal neurons produced
      responses that were consistent with the activation of TRPV1 receptors.

PMID- 19865708
TI  - The reaction of acyl cyanides with "Huisgen zwitterion": an interesting
      rearrangement involving ester group migration between oxygen and nitrogen atoms.
AB  - A novel rearrangement involving ester group migration was found in the reaction
      of acyl cyanides and Huisgen zwitterions, affording hydrazone derivatives at
      higher temperature (90 degrees C) and azine derivatives at lower temperature (20
      degrees C), respectively. Interestingly, the reaction temperature is identified
      as a critical factor to control the final products. Presumably, the rearrangement
      involving ester group migration between oxygen and nitrogen atoms leads to the
      formation of different products.

PMID- 19865709
TI  - Phenylenediamine-based bivalent glycocyclophanes: synthesis and analysis of the
      influence of scaffold rigidity and ligand spacing on lectin binding in cell
      systems with different glycomic profiles.
AB  - The conjugation of carbohydrates to synthetic scaffolds has the goal of preparing
      potent inhibitors of lectin binding. We herein report the synthesis of a panel of
      bivalent compounds (cyclophane and terephthalamide-derivatives) then used to
      establish the influence of scaffold flexibility on respective inhibitory potency
      in a medically relevant test system. Synthetic routes to two phenylenediamine
      based glycocyclophanes involving Ugi reactions of glucuronic acid derivatives and
      subsequent ring closing metathesis are described, as are improvements for
      producing terephthalamide-based carbohydrate carriers. Assays were performed with
      human tumour cells measuring quantitatively the influence of the test compounds
      on fluorescent surface staining by labelled lectins. Biological evaluation using
      two different lines of cancer cells as well as cells with known alterations in
      the glycomic profile (cells treated with an inhibitor of glycan processing and a
      glycosylation mutant) reduced the risk of generating premature generalizations
      regarding inhibitor potency. Bioactivity relative to free mannose was invariably
      determined for the synthetic compounds. A clear trend for enhanced inhibitory
      properties for macrocyclic compounds compared to non-macrocyclic derivatives was
      discerned for one type of glycocyclophane. Herein we also document the impact of
      altering the spacing between the mannose residues, altering cell surface ligand
      density and cell-type reactivity. The applied strategy for the cell assays is
      proposed to be of general importance in the quest to identify medically relevant
      lectin inhibitors.

PMID- 19865710
TI  - N-Hexyl-4-aminobutyl glycosides for investigating structures and biological
      functions of carbohydrates.
AB  - The potential applications of N-hexyl-4-aminobutyl glycosides in the mass
      spectrometric investigation of glycan structure and in the investigation of
      glycan functions were studied. Under collision-induced dissociation (CID)
      conditions, sodiated glycosides carrying N-hexyl-4-aminobutyl groups effectively
      produced a hemiacetal species (C-ions), which is important in mass-spectrometry
      based structural investigation. The usefulness of N-hexyl-4-aminobutyl glycosides
      in biological analysis was also confirmed by obtaining a binding constant for the
      binding of dipyrrometheneboron difluoride C3-labeled N-hexyl-4-aminobutyl beta
      lactoside with an Erythrina cristagalli lectin, and by visualizing cellular
      organelles using a more hydrophobic BODIPY-labeled compound.

PMID- 19865711
TI  - Four-fold click reactions: Generation of tetrahedral methane- and adamantane
      based building blocks for higher-order molecular assemblies.
AB  - A modular concept for the generation of achiral and chiral non-racemic
      tetrahedral tectons from common precursors was developed. The tectons presented
      here are based on tetraphenylmethane or 1,3,5,7-tetraphenyladamantane core
      structures. They are obtained through high-yielding four-fold click reactions,
      using either the tetraazido or the tetraalkyne precursors. In most cases, the
      tetratriazoles are obtained as pure products after simple washing with water and
      methanol. The side chains of the tectons prepared include a self-complementary
      DNA dimer, obtained from a 3'-azidonucleoside and a phosphoramidite. The concept
      allows for a variation of the "sticky ends", leading to tecton or ligand
      libraries.

PMID- 19865712
TI  - Geometry-dependent divergence in the gold-catalyzed redox cascade cyclization of
      o-alkynylaryl ketoximes and nitrones leading to isoindoles.
AB  - We report geometry-dependent cyclizations of o-alkynylaryl ketoximes and nitrones
      catalyzed by gold complexes. (E)-Ketoximes undergo N-attack to give isoquinoline
      N-oxides. In sharp contrast, (Z)-ketoximes undergo unprecedented O-nucleophilic
      attack, followed by a redox cascade leading to a novel catalytic entry to
      isoindoles of diverse scope. The structure of an isoindole was unambiguously
      supported by X-ray crystallography. We demonstrated the generality of the
      isoindole synthesis from either (Z)-oximes or nitrones, and presented a
      mechanistic model of this redox cascade based on the reaction profiles of various
      substrates.

PMID- 19865713
TI  - Exploring synthetic avenues for the effective synthesis of selenium- and
      tellurium-containing multifunctional redox agents.
AB  - Various human illnesses, including several types of cancer and infectious
      diseases, are related to changes in the cellular redox homeostasis. During the
      last decade, several approaches have been explored which employ such disturbed
      redox balances for the benefit of therapy. Compounds able to modulate the
      intracellular redox state of cells have been developed, which effectively, yet
      also selectively, appear to kill cancer cells and a range of pathogenic
      microorganisms. Among the various agents employed, certain redox catalysts have
      shown considerable promise since they are non-toxic on their own yet develop an
      effective, often selective cytotoxicity in the presence of the 'correct'
      intracellular redox partners. Aminoalkylation, amide coupling and multicomponent
      reactions are suitable synthetic methods to generate a vast number of such
      multifunctional catalysts, which are chemically diverse and, depending on their
      structure, exhibit various interesting biological activities.

PMID- 19865714
TI  - Synthetic dinucleotide mRNA cap analogs with tetraphosphate 5',5' bridge
      containing methylenebis(phosphonate) modification.
AB  - An effective and facile synthesis of six novel tetraphosphate cap analogs
      modified with a methylenebis(phosphonate) moiety (1-6) is presented. Analogs have
      been rationally designed to bind tightly to the eukaryotic initiation factor 4E
      (eIF4E) responsible for cap binding during the initiation of translation, and
      have increased stability owing to resistance to enzymatic degradation. Final
      compounds turned out to have significantly higher association constant values
      (K(AS)) for binding to eIF4E (5-9 fold higher than standard). Four of the analogs
      were resistant towards enzymatic degradation by human Decapping Scavenger enzyme
      (DcpS). Binding studies of non-hydrolyzable analogs with DcpS revealed a broad
      range of K(AS) values for different analogs. All of the analogs were potent
      inhibitors of translation in a rabbit reticulocyte lysate system (RRL) and those
      resistant to DcpS turned out to be stable under an elongated time of
      preincubation while the inhibitory potency of standard was diminished in these
      conditions. For Anti Reverse Cap Analog (ARCA) dinucleotides (4-6), we have shown
      that they are effectively incorporated into mRNA and transcripts capped with
      these analogs undergo translation in vitro.

PMID- 19865715
TI  - Rediscovering copper-based catalysts for intramolecular carbon-hydrogen bond
      functionalization by carbene insertion.
AB  - A series of Tp(x)Cu complexes (Tp(x) = hydrotrispyrazolylborate ligand) have been
      tested as catalysts for the decomposition of several diazoacetates and N,N
      disubstituted diazoacetamides and the subsequent formation of lactones and
      lactams, respectively. The complexes containing the ligands Tp(Br3) or Tp(Ms)
      have provided activities and selectivities for these transformations comparable
      with or, in some cases, better than the well-known rhodium catalyst
      Rh(2)(OAc)(4).

PMID- 19865716
TI  - Substitution effect on the hydrofluorination reaction of unsaturated amines in
      superacid HF/SbF(5).
AB  - This paper describes the scope and limitations of the hydrofluorination reaction
      in superacid HF/SbF(5). On the basis of experimental studies of polyfunctional
      substrates' behaviour, the dramatic effect of substitution on the
      superelectrophilic character of ammonium-carbenium dications was emphasized. This
      reaction was applied to the synthesis of novel fluorinated key building blocks.
      Furthermore, the hydrofluorination reaction and the discovered
      homodimerization/fluorination reaction were applied to the synthesis of highly
      valued fluorinated diamines.

PMID- 19865723
TI  - A robust electrical microcytometer with 3-dimensional hydrofocusing.
AB  - In this paper, we present a device to electrically count blood cell populations
      using an AC impedance interrogation technique in a microfabricated cytometer
      (microcytometer). Specifically, we direct our attention to obtaining the
      concentration of human CD4+ T lymphocytes (helper T cells), which is a necessary
      method to diagnose patients for HIV/AIDS and to give an accurate prognosis on the
      effectiveness of ARV (anti-retroviral) drug treatments. We study the
      effectiveness of a simple-to-fabricate 3-dimensional (3D) hydrodynamic focusing
      mechanism through fluidic simulations and corresponding experiments to increase
      the signal-to-noise ratio of impedance pulses caused by particle translocation
      and ensure lower variance in particle translocation height through the electrical
      sensing region. We found that the optimal 3D sheath flow settings result in a
      44.4% increase in impedance pulse signal-to-noise ratio in addition to giving a
      more accurate representation of particle size distribution. Our microcytometer T
      cell counts closely with those found using an industry-standard flow cytometer
      for the concentration range of over three orders of magnitude and using a sample
      volume approximately the size of a drop of blood (approximately 20 microL). In
      addition, our device displayed the capability to differentiate between live and
      dead/dying lymphocyte populations. This microcytometer can be the basis of a
      portable, rapid, inexpensive solution to obtaining live/dead blood cell counts
      even in the most resource-poor regions of the world.

PMID- 19865724
TI  - Towards a human-on-chip: culturing multiple cell types on a chip with
      compartmentalized microenvironments.
AB  - We have developed a multi-channel 3D microfluidic cell culture system (multi
      channel 3D-microFCCS) with compartmentalized microenvironments for potential
      application in human drug screening. To this end, the multi-channel 3D-microFCCS
      was designed for culturing different 3D cellular aggregates simultaneously to
      mimic multiple organs in the body. Four human cell types (C3A, A549, HK-2 and
      HPA) were chosen to represent the liver, lung, kidney and the adipose tissue,
      respectively. Cellular functions were optimized by supplementing the common
      medium with growth factors. However, TGF-beta1 was found to enhance A549
      functions but inhibit C3A functions. Therefore, TGF-beta1 was specifically
      controlled-released inside the A549 compartment by means of gelatin microspheres
      mixed with cells, thus creating a cell-specific microenvironment. The function of
      A549 cells was enhanced while the functions of C3A, HK-2 and HPA cells were
      uncompromised, demonstrating the limited cross-talk between cell culture
      compartments similar to the in vivo situation. Such a multi-channel 3D-microFCCS
      could be potentially used to supplement or even replace animal models in drug
      screening.

PMID- 19865725
TI  - A continuous high-throughput bioparticle sorter based on 3D traveling-wave
      dielectrophoresis.
AB  - We present a high throughput (maximum flow rate approximately 10 microl/min or
      linear velocity approximately 3 mm/s) continuous bio-particle sorter based on 3D
      traveling-wave dielectrophoresis (twDEP) at an optimum AC frequency of 500 kHz.
      The high throughput sorting is achieved with a sustained twDEP particle force
      normal to the continuous through-flow, which is applied over the entire chip by a
      single 3D electrode array. The design allows continuous fractionation of micron
      sized particles into different downstream sub-channels based on differences in
      their twDEP mobility on both sides of the cross-over. Conventional DEP is
      integrated upstream to focus the particles into a single levitated queue to allow
      twDEP sorting by mobility difference and to minimize sedimentation and field
      induced lysis. The 3D electrode array design minimizes the offsetting effect of
      nDEP (negative DEP with particle force towards regions with weak fields) on twDEP
      such that both forces increase monotonically with voltage to further increase the
      throughput. Effective focusing and separation of red blood cells from debris
      filled heterogeneous samples are demonstrated, as well as size-based separation
      of poly-dispersed liposome suspensions into two distinct bands at 2.3 to 4.6
      microm and 1.5 to 2.7 microm, at the highest throughput recorded in hand-held
      chips of 6 microl/min.

PMID- 19865726
TI  - Microinjection in a microfluidic format using flexible and compliant channels and
      electroosmotic dosage control.
AB  - We present a novel PDMS-based microinjection system in a microfluidic format with
      precise electroosmotic dosage control. The device architecture is fully scalable
      and enables high-throughput microinjections with integrated pre- and post
      processing operations. The injection mechanism greatly simplifies current methods
      as only a single degree of freedom is required for injections. The injections are
      performed inside a fully enclosed channel by an integrated microneedle. Actuation
      of the needle is achieved by the compliant deformation of the channel structure
      by an external actuator. Reagent transport is achieved using electroosmotic flow
      (EOF) which provides non-pulsating flow and precise electrical dosage control.
      The potentials used for injections were between 5 V-25 V. The electrical
      properties and flow rates for the device were characterized for Zebrafish embryos
      and Rhodamine B and Methylene blue in pH 10 buffer solution. We also propose a
      method to enable precise individual dosing of embryos using direct electrical
      feedback. Additionally, we show that electrical feedback can be used to verify
      the location of the needle inside the injection target. A preliminary viability
      study of our device was conducted using Zebrafish (Danio rerio) embryos. The
      study involved the injection of ultrapure water into the embryos in an E3 buffer,
      and resulted in embryos that showed normal development at 48 hours.

PMID- 19865727
TI  - Enhancing DNA hybridization kinetics through constriction-based
      dielectrophoresis.
AB  - The enhancement of signal sensitivity through the scaling-down of sensors
      presents mass transport limitations that can arrest the sensitivity gains
      obtained as a result of miniaturization. To alleviate these limitations, we study
      the application of constriction-based dielectrophoresis methods to enhance
      transport through pre-concentration of target DNA in the vicinity of the
      diffusion layer of the sensor, on which capture probe DNA molecules were
      immobilized. We demonstrate that constriction-based DEP pre-concentration was not
      impeded by scaling-down of the sensor, as long as the sensor electrode was
      composed of nanostructured edges and was coupled to an equally scaled down
      insulating constriction within a microfluidic channel to enhance the focusing
      effects of the constrictions and edges. Furthermore, as a result of the high
      focusing fields, pre-concentration of single-stranded target DNA occurred in the
      vicinity of the sensor pad within the relatively high ionic strength buffers
      required for DNA hybridization, with minimal degradation of capture probe
      molecules. Finally, constriction-based DEP resulted in an almost immediate pre
      concentration of target DNA in the vicinity of the sensor electrode diffusion
      layer, resulting in a ten-fold enhancement of the DNA hybridization kinetics at
      target concentration values down to the sensitivity limit of 10 pM for the sensor
      platform.

PMID- 19865728
TI  - Integration and application of vitrified collagen in multilayered microfluidic
      devices for corneal microtissue culture.
AB  - This paper describes the fabrication and application of microfluidic devices
      containing collagen vitrigel (CV) used as both a functional and sacrificial cell
      growth substrate for the development of corneal microtissue patches. Within the
      device, vacuum fixation of the CV in a dehydrated state enables quick integration
      with standard multilayer soft lithographic techniques, while on-chip rehydration
      results in a gel-like collagen substrate for microfluidic cell culture. Fluidic
      connectivity to both the apical and basal side of the CV permits bilayered
      culture of epithelium and supporting stromal cell layers. In addition,
      microfluidic introduction of a collagenase etching media enables sacrificial
      degradation of the supporting CV membrane for development of barrier tissue
      constructs containing minimal synthetic substrate. The utility of this platform
      was evaluated by miniaturizing the standard transepithelial permeability (TEP)
      assay in order to measure the integrity of an array of corneal tissue
      micropatches.

PMID- 19865729
TI  - A light-induced dielectrophoretic droplet manipulation platform.
AB  - We report on a light-actuated, droplet based microfluidic platform enabling two
      dimensional (2D) droplet manipulation on an open chamber with a single-side,
      featureless photoconductive surface. The droplet actuation mechanism is based on
      recently demonstrated floating electrode optoelectronic tweezers (FEOET), which
      enable light-induced dielectrophoretic forces to manipulate aqueous droplets
      immersed in electrically nonconductive oil, with a light intensity as low as 400
      microW/cm2. In this paper, we study the shape effect of optical patterns for 2D
      droplet actuation, and demonstrate light-actuated droplet manipulation functions
      including 2D droplet transport, merging, mixing, and multidroplet processing, for
      up to 16 droplets in parallel. Such an open chamber platform also permits easy
      interfacing and integration with other microfluidic structures, such as wells and
      close-channel based droplet devices to increase its versatility for biochemical
      analyses.

PMID- 19865730
TI  - Agarose microwell based neuronal micro-circuit arrays on microelectrode arrays
      for high throughput drug testing.
AB  - For cell-based biosensor applications, dissociated neurons have been cultured on
      planar microelectrode arrays (MEAs) to measure the network activity with
      substrate-embedded microelectrodes. There has been a need for a multi-well type
      platform to reduce the data collection time and increase the statistical power
      for data analysis. This study presents a novel method to convert a conventional
      MEA into a multi-well MEA with an array of micrometre-sized neuronal culture
      ('neuronal micro-circuit array'). An MEA was coated first with cell-adhesive
      layer (poly-D-lysine) which was subsequently patterned with a cell-repulsive
      layer (agarose hydrogel) to both pattern the cell adhesive region and isolate
      neuronal micro-circuits from each other. For a few weeks, primary hippocampal
      neurons were cultured on the agarose microwell MEA and the development of
      spontaneous electrical activities were characterized with extracellular action
      potentials. Using neurotransmission modulators, the simultaneous monitoring of
      drug responses from neuronal micro-circuit arrays was also demonstrated. The
      proposed approach will be powerful for neurobiological functional assay studies
      or neuron-based biosensor fields which require repeated trials to obtain a single
      data point due to biological variations.

PMID- 19865731
TI  - Microfluidic system with integrated electroosmotic pumps, concentration gradient
      generator and fish cell line (RTgill-W1)--towards water toxicity testing.
AB  - This study presents a microfluidic system that incorporates electroosmotic pumps,
      a concentration gradient generator and a fish cell line (rainbow trout gill) to
      perform toxicity testing on fish cells seeded in the system. The system consists
      of three mechanical components: (1) a toxicity testing chip containing a
      microfluidic gradient generator which creates a linear concentration distribution
      of toxicant in a cell test chamber, (2) an electroosmotic (EO) pump chip that
      controls the flow rate and operation of the toxicity chip, and (3) indirect
      reservoirs that connect the two chips allowing for the toxicant solution to be
      pumped separately from the electroosmotic pump solution. The flow rate and
      stability of the EO pumps was measured and tested by monitoring the gradient
      generator using fluorescence microscopy. Furthermore, a lethality test was
      performed with this system setup using a rainbow trout gill cell line (RTgill-W1)
      as the test cells and sodium dodecyl sulfate as a model toxicant. A gradient of
      sodium dodecyl sulfate, from 0 to 50 microg mL(-1), was applied for 1 hr to the
      attached cells, and the results were quantified using a Live/Dead cell assay.
      This work is a preliminary study on the application of EO pumps in a living cell
      assay, with the potential to use the pumps in portable water quality testing
      devices with RTgill-W1 cells as the biosensors.

PMID- 19865732
TI  - A micro surface tension alveolus (MISTA) in a glass microchip.
AB  - We have designed a non-membrane micro surface tension alveolus (MISTA) in a glass
      microchip for direct gas exchange and micro gradient control. Hemoglobin (Hb) in
      the liquid phase indicates the rapid gas gradient changes of O2 and CO2 shifted
      by the difference in pressure between the liquid and the gas.

PMID- 19865733
TI  - Multi-curvature liquid meniscus in a nanochannel: evidence of interplay between
      intermolecular and surface forces.
AB  - We examined the formation of a multiply curved meniscus inside rectangular
      nanochannels, whose width ranges from 50 to 800 nm at a constant height of 200
      nm. When the channel width is smaller than approximately 400 nm under partial
      wetting conditions, a distinct multi-curvature meniscus was observed at the
      advancing front with an edge disjoined from the wall. In contrast, a typical pre
      wetting film was observed at the front regardless of the channel size for
      complete wetting conditions. Our theoretical analysis demonstrated that the multi
      curvature meniscus is generated from the increased contribution of an extra
      pressure due to intermolecular interactions near the wall. In particular, a plug
      like meniscus profile was observed at the advancing liquid front for the 50 nm
      wide channel owing to an overlap between convex curvatures at the channel walls.
      Finally, we showed that the filling velocity of liquid can be decreased by
      decreasing the channel size due to the reduced wettability.

PMID- 19865734
TI  - On-chip immuno-agglutination assay with analyte capture by dynamic manipulation
      of superparamagnetic beads.
AB  - Magnetic bead-based lab-on-a-chip systems offer significant advantages compared
      to more conventional systems, mainly through the possibility of controlled
      manipulation of the magnetic carriers on-chip. In particular, microfluidic
      immunoassays using functionalized magnetic beads raise increasing interest. We
      present here a new approach for performing immuno-agglutination assays on-chip.
      Our system is based on a quadrupolar magnetic field set-up. Dynamic actuation of
      a confined plug of functionalized magnetic beads is used for analyte capture in a
      microchannel. A simple detection method based on the swelling of the released
      plug after agglutination is presented. We demonstrate the feasibility of on-chip
      agglutination tests by means of a streptavidin/biotinylated-bovine serum albumin
      (bBSA) model assay. A detection limit of about 200 pg/mL (approximately 3 pM) is
      achieved.

PMID- 19865735
TI  - Electric field directed assembly of high-density microbead arrays.
AB  - We report a method for rapid, electric field directed assembly of high-density
      protein-conjugated microbead arrays. Photolithography is used to fabricate an
      array of micron to sub-micron-scale wells in an epoxy-based photoresist on a
      silicon wafer coated with a thin gold film, which serves as the primary
      electrode. A thin gasket is used to form a microfluidic chamber between the wafer
      and a glass coverslip coated with indium-tin oxide, which serves as the counter
      electrode. Streptavidin-conjugated microbeads suspended in a low conductance
      buffer are introduced into the chamber and directed into the wells via
      electrophoresis by applying a series of low voltage electrical pulses across the
      electrodes. Hundreds of millions of microbeads can be permanently assembled on
      these arrays in as little as 30 seconds and the process can be monitored in real
      time using epifluorescence microscopy. The binding of the microbeads to the gold
      film is robust and occurs through electrochemically induced gold-protein
      interactions, which allows excess beads to be washed away or recycled. The well
      and bead sizes are chosen such that only one bead can be captured in each well.
      Filling efficiencies greater than 99.9% have been demonstrated across wafer-scale
      arrays with densities as high as 69 million beads per cm(2). Potential
      applications for this technology include the assembly of DNA arrays for high
      throughput genome sequencing and antibody arrays for proteomic studies. Following
      array assembly, this device may also be used to enhance the concentration
      dependent processes of various assays through the accelerated transport of
      molecules using electric fields.

PMID- 19865737
TI  - Controllable preparation of microscale tubes with multiphase co-laminar flow in a
      double co-axial microdevice.
AB  - This article describes a simple method for the fabrication of microscale polymer
      tubes. A double co-axial microchannel device was designed and fabricated.
      Liquid/liquid/liquid multiphase co-laminar flows were realized in a microchannel
      by choosing working systems. Three kinds of polymeric solutions were selected as
      the middle phase while a polyethyleneglycol aqueous solution was used as the
      inner and outer phases in the microfluidic process. The outer and inner phases
      acted as extractants of the polymer solvent. A stable double core-annular flow
      was formed by optimizing the composition of the outer and inner phases, and
      highly uniform tubes were successfully fabricated by the solvent extraction
      method. Both the outer diameter of the tubes and the wall thickness could be
      adjusted from 300 microm to 900 microm and from 40 microm to 150 microm by
      varying the flux of the fluids and the rolling velocity of the collection roller.
      In addition, titanium dioxide (TiO2) nanoparticles were successfully encapsulated
      into the polymer tubes with this technique. This technology has the potential to
      generate hollow fiber membranes for applications in separation and reaction
      processes.

PMID- 19865738
TI  - Microfluidics with on-line dynamic light scattering for size measurements.
AB  - We present a detailed investigation on the feasibility of on-line dynamic light
      scattering measurements of colloidal sizes in a pressure-driven microfluidic
      flow. We review some theoretical arguments showing that such experiments are
      difficult to perform due to the Poiseuille flow that induces interferences of
      different Doppler shifts. Such a theoretical approach is however very useful to
      figure out the range of parameters where on-line size measurements are possible.
      We then build a dynamic light scattering setup around a microfluidic chip that
      enables us to estimate the size of Brownian scatterers flowing in PDMS-based
      microchannels, thus validating experimentally the theoretical estimations. We
      finally present a microfluidic chip that can mix two reactants in approximately
      200 ms, and allows size measurements using dynamic light scattering at about 300
      ms after complete mixing. Two applications are presented: the continuous
      monitoring of the viscosity of a two-fluid mixture, and the electrostatic co
      assembly of oppositely charged nanoparticles and block copolymers.

PMID- 19865736
TI  - Lab-on-a-chip for botulinum neurotoxin a (BoNT-A) activity analysis.
AB  - A Lab-on-a-chip (LOC) was designed, fabricated and tested for the in vitro
      detection of botulinum neurotoxin serotype A (BoNT-A) activity using an assay
      that measures cleavage of a fluorophore-tagged peptide substrate specific for
      BoNT-A (SNAP-25) by the toxin light chain (LcA). LcA cleavage was detected by
      Forster Resonance Energy Transfer (FRET) fluorescence. FRET fluorescence was
      measured by a newly developed portable charge-coupled device (CCD) fluorescent
      detector equipped with multi-wavelength light-emitting diodes (LED) illumination.
      An eight V-junction microchannel device for BoNTs activity assays was constructed
      using Laminated Object Manufacturing (LOM) technology. The six-layer device was
      fabricated with a Poly(methyl methacrylate (PMMA) core and five polycarbonate
      (PC) layers micromachined by CO2 laser. The LOC is operated by syringe and is
      equipped with reagents, sample wells, reaction wells, diffusion traps (to avoid
      cross contamination among channels) and waste reservoirs. The system was detected
      LcA at concentrations as low as 0.5 nM, which is the reported sensitivity of the
      SNAP-25 in vitro cleavage assay. Combined with our CCD detector, the simple point
      of care system enables the detection of BoNTs activity and may be useful for the
      performance of other complex medical assays without a laboratory. This approach
      may realize the potential to enhance the quality of health care delivery for
      underserved populations.

PMID- 19865739
TI  - SNP genotyping of unpurified PCR products by sandwich-type affinity
      electrophoresis on a microchip with programmed autonomous solution filling.
AB  - We demonstrate rapid single-nucleotide polymorphism (SNP) genotyping on a
      poly(dimethylsiloxane)-glass microchip. Sandwich-type affinity electrophoresis
      was employed to achieve sufficient specificity for reliable genotyping of
      unpurified PCR products. We tested three SNPs in different genes: CYP2D6 of
      artificial templates, and ALDH3A1 and CYP1A1 of human genomic samples. The target
      sequences were amplified by asymmetric PCR. For each SNP, we prepared a capture
      probe-poly(dimethylacrylamide) (CP-PDMA) conjugate and allele-specific,
      fluorescently-labeled detection probes (DPs). Prior to the electrophoresis,
      necessary solutions--the amplified sample, the CP-PDMA conjugate, the DPs, and a
      washer--were autonomously filled into their own regions of the microchannel in
      contact with each other. For precise control of this filling process, we have
      extended our published technique to a "programmed" version, in which additional
      passive stop valves synchronized the solution contacting events. Then we
      electrophoretically carried out a target DNA hybridization step, a DP
      hybridization step, and a washing step at the CP-PDMA conjugate region. This 3
      step electrophoresis was completed in 2 min. The formation of the sandwich
      hybridization complex (CP-target-DP) was evaluated by fluorescence. Normalized
      fluorescence values of the different genotypes were clearly and reproducibly
      discriminated. The assay format presented here will be suitable for SNP
      genotyping at the point of care.

PMID- 19865740
TI  - Multidimensional modular microfluidic system.
AB  - An extension of our previous work on a genuinely plug-n-play modular microfluidic
      system is presented for designing and building customized multidimensional
      (planar, three-dimensional (3D) and their combinations) microfluidic systems as
      well as for better system integration by allowing direct plug-in of active
      components such as micropumps.

PMID- 19865741
TI  - Fabricating small-scale, curved, polymeric structures with convex and concave
      menisci through interfacial free energy equilibrium.
AB  - Polymeric curved structures are widely used in imaging systems including optical
      fibers and microfluidic channels. Here, we demonstrate that small-scale,
      poly(dimethylsiloxane) (PDMS)-based, curved structures can be fabricated through
      controlling interfacial free energy equilibrium. Resultant structures have a
      smooth, symmetric, curved surface, and may be convex or concave in form based on
      surface tension balance. Their curvatures are controlled by surface
      characteristics (i.e., hydrophobicity and hydrophilicity) of the molds and semi
      liquid PDMS. In addition, these structures are shown to be biocompatible for cell
      culture. Our system provides a simple, efficient and economical method for
      generating integrateable optical components without costly fabrication
      facilities.

PMID- 19865746
TI  - The formation of equilibrium space-charge zones at grain boundaries in the
      perovskite oxide SrTiO3.
AB  - The thermodynamics of space-charge formation at grain boundaries in acceptor
      doped SrTiO(3) is examined. Thermodynamic models of varying complexity are
      developed, which predict the space-charge potential as a function of
      thermodynamic variables, such as dopant concentration, temperature and oxygen
      partial pressure. Based on the results, limits to the space-charge potential that
      can arise at a grain boundary and strategies for tuning the space-charge
      potential are discussed. With literature equations linking the space-charge
      potential to electrical properties, one specific thermodynamic model is
      subsequently applied to electrical impedance data reported in the literature for
      tilt bicrystal samples of Fe-doped SrTiO(3). The thermodynamic driving energies
      for space-charge formation obtained from the analysis are examined as a function
      of tilt misorientation angle, in order to explore the relationship between
      driving energy and interface atomistic structure. In addition, the capabilities
      and deficiencies of the entire approach (from driving energies via space-charge
      potentials to electrical properties), with regard to predicting experimental
      behaviour, are demonstrated.

PMID- 19865747
TI  - Experimental and theoretical evidence of charge transfer in weakly bound
      complexes of water.
AB  - We report the definitive assessment of a measurable (half a kJ/mol) charge
      transfer (CT) component in the interaction of water with the noble gases. The CT
      is found to be strongly stereoselective and is mediated by a highly asymmetric,
      donor/acceptor concerted role of the two hydrogen atoms, which can in fact
      dictate the equilibrium geometry of the adducts. This finding may be of general
      relevance in explaining the known peculiar orientational features of water's
      interactions. By using an original method of partial integration of the change in
      electron density occurring upon the formation of Ng-water complexes (computed
      with accurate ab initio methods and basis sets), we map the local charge
      displacement along the whole intermolecular region and are thus able to appraise
      CT effects free of the inherent ambiguity of charge decomposition models. With
      this, it was possible to prove that a small CT (of the order of a couple of
      millielectrons at most) takes place from Ng to water. Most importantly, this CT
      correlates quantitatively with some unexpected "glory" quantum interference
      effects observed in high-resolution molecular-beam Ng-water scattering
      experiments that indicate a stronger bond than a pure van der Waals force. The
      energy stabilization associated with the observed CT does not exceed half a kJ
      mol(-1). The Ng-water CT is found to be strongly stereoselective and is mediated
      by a highly asymmetric, donor-acceptor concerted role of the two hydrogen atoms,
      which can in fact dictate the equilibrium geometry of the adducts. This finding
      may be of general relevance in explaining the known peculiar orientational
      features of water's interactions.

PMID- 19865748
TI  - Water activation by SO2(*+) ions: an effective source of OH* radicals.
AB  - A novel O-H bond activation reaction is reported: thermal SO(2)(*+) radical
      cations activate water in the gas phase forming OH* radicals with 100%
      efficiency.

PMID- 19865749
TI  - Hydration of phospholipid interface: carbonyl-water hydrogen bond association.
AB  - Being largely driven by electrostatic interactions, hydration compensates
      hydrophobic repulsion and, thus, contributes decisively in structural expressions
      of molecules in a phospholipid membrane environment. Here, we explore the nature
      of the aqueous state associated with carbonyl moieties of a phospholipid bilayer.
      The task is of an obvious difficulty, since water clustering at a membrane
      interface implies the presence of various aqueous states giving rise to spectral
      inhomogeneity. The resultant frequency overlap of the optical response from
      states of differing nature obscures the structural analysis. We extract the
      information on water next to phospholipid carbonyls by monitoring the O-D stretch
      perturbation upon direct infrared excitation of lipid carbonyl groups. Modelling
      the signal with the help of quantum computations and molecular dynamics
      simulation, we extract the geometry for the optimal placement of water next to
      carbonyl moieties, and anticipate the time scale of the water molecule
      displacement, leading to the disruption of the hydrogen bond, upon direct
      excitation of the C=O group. The picture we provide here is of general and
      applied value. The practical importance stems from the necessity of
      experimentally characterizing the hydration of polar moieties in polypeptides (of
      pharmacological significance) when in a phospholipid environment, a task not yet
      achieved.

PMID- 19865750
TI  - An XAS experimental approach to study low Pt content electrocatalysts operating
      in PEM fuel cells.
AB  - We present an X-ray absorption spectroscopy (XAS) study of a low Pt content
      catalyst layer (Pt loading 0.1 mg cm(-2)) operating at the cathode of a proton
      exchange membrane fuel cell (PEMFC). This catalyst is based on the use of a
      mesoporous inorganic matrix as a support for the catalyst Pt nanoparticles. Due
      to the high Pt dilution, in situ measurements of its structural properties by XAS
      are challenging and suitable experimental strategies must be devised for this
      purpose. In particular, we show that accurate XAS in situ fluorescence
      measurements can be obtained using an optimized fuel cell, suitable protocols for
      alignment of a focused X-ray beam and an appropriate filter for the background
      signal of the other atomic species contained in the electrodes. Details,
      advantages and limitations of the XAS technique for in situ measurements are
      discussed. Analysis of the near-edge XAS and EXAFS (extended X-ray absorption
      fine structure) data, corroborated by a HRTEM (high-resolution transmission
      electron microscopy) study, shows that the Pt particles have a local structure
      compatible with that of bulk Pt (fcc) and coordination numbers match those
      expected for particles with typical sizes in the 1.5-2.0 nm range. Substantial
      changes in the oxidation state and in local atomic arrangement of the Pt
      particles are found for different applied potentials. The catalyst support,
      containing W atoms, exhibits a partial reduction upon PEMFC activation, thus
      mimicking the catalyst behavior. This indicates a possible role of the mesoporous
      matrix in favouring the oxygen reduction reaction (ORR) and stimulates further
      research on active catalyst supports.

PMID- 19865752
TI  - Structural evolution and properties of subnanometer Tc(n) (n = 2-15) clusters.
AB  - All-electron scalar relativistic calculations of the geometric and electronic
      structures of neutral subnanometer Tc(n) (n = 2-15) clusters have been performed
      using spin-polarized density functional theory. It is shown that the structural
      evolution of Tc(n) clusters from n = 3 to n = 8 is similar to Mn clusters, which
      also belong to the group of VIIB transition metals. The calculated binding energy
      per atom varies gradually from 0.65 eV for Tc(2) to 2.35 eV for Tc(15). The
      computed electron affinity and ionization potential follow the classical
      electrostatic metallic droplet model for clusters larger than Tc(6) and converge
      asymptotically to the experimental value of the bulk Tc work function. A study of
      the kinetic stability of Tc clusters in terms of the second difference of binding
      energies and the energy gap between the frontier orbital states predicts
      Tc(3)(D(3h)), Tc(4)(T(d)), Tc(6)(O(h)), Tc(12)(I(h)), and Tc(13)(I(h)) to be the
      most stable clusters. Vibrational spectra of Tc clusters are also provided for
      further experimental identification.

PMID- 19865751
TI  - Photoabsorption studies of neutral green fluorescent protein model chromophores
      in vacuo.
AB  - We report on gas-phase experimental and theoretical studies on the neutral form
      of the green-fluorescent protein (GFP) chromophore using six different models,
      each carrying a spectator positive charge. Theoretical studies were carried out
      to quantify the effect of the spectator charge on the absorption maximum of the
      true neutral. The study also includes models having the possibility of forming
      intra-molecular hydrogen bonds, and their effect on the absorption profile is
      analyzed. The charge redistribution caused by a strong intra-molecular hydrogen
      bond was found to give rise to a red shift in going from non-hydrogen bonded to
      hydrogen bonded models. For the non-hydrogen bonded models, the length of the
      side chain as well as the group carrying the spectator charge, was varied to
      explore the possibility of shifts in absorption maximum due to these variations.
      No shifts were observed. The implications of these results in tuning the
      absorption maximum of the neutral form of the GFP chromophores are discussed.

PMID- 19865753
TI  - Interactions between co-adsorbed CO and H on a Rh(100) single crystal surface.
AB  - Co-adsorption of CO and H(2) on a Rh(100) single crystal surface has been studied
      by a combination of temperature programmed desorption (TPD), reflection
      absorption infrared spectroscopy (RAIRS), low energy electron diffraction (LEED),
      and density functional theory (DFT) calculations. Exposure of CO to a hydrogen
      precovered surfaces at 150 K results in some displacement of adsorbed hydrogen
      and a layer with 0.67 ML H and 0.67 ML CO is obtained. A c(3 square root(2) x
      square root(2))R45 degree structure is formed with CO occupying bridge sites and
      hydrogen occupying partly bridge sites on the surface and partly octahedral
      subsurface sites, causing hydrogen to desorb at temperatures around 230 K.

PMID- 19865754
TI  - Molecular dynamics simulations of polyamidoamine dendrimers and their complexes
      with linear poly(ethylene oxide) at different pH conditions: static properties
      and hydrogen bonding.
AB  - Models consisting of an amine-terminated poly(amidoamine) (PAMAM) dendrimer with
      and without the presence of a linear poly(ethylene oxide) (PEO) chain were
      studied in aqueous solutions by means of fully atomistic molecular dynamics
      simulations. Dendrimers of two generations, 3rd and 4th and at different pH
      conditions were examined, in order to address issues associated with
      characteristics pertinent to the shape of the dendrimers in the presence or
      absence of PEO as well as to the volume fraction of the penetrating solvent
      molecules and counterions as compared to recent experimental studies. In
      addition, hydrogen-bonding characteristics such as the intensity and the
      longevity of intra- and intermolecular hydrogen-bonded pairs are examined for the
      first time in these systems. It was found that the volume fraction of the
      penetrating solvent molecules increased upon decrease of pH, but no dependence on
      the size of the molecules was observed. The density of the solvent within the
      dendritic interior did not exceed that of the bulk, while the corresponding
      number of counterions entering the dendrimer boundaries exhibited a marked
      increase between the 3rd and the 4th generation of the dendrimers. Intramolecular
      hydrogen bonding was favored at high pH conditions, while intermolecular hydrogen
      bonding between PAMAM and the solvent or the PEO was significantly enhanced upon
      protonation of the dendrimer's amines. The presence of PEO imparted appreciable
      changes in the dendrimer's shape particularly in the physiological pH conditions.
      In addition, it incurred a decrease in intramolecular hydrogen bonding and acted
      antagonistically to the formation of water/dendrimer hydrogen bonds. The higher
      degree of hydrogen bonding between PAMAM and PEO was observed at low pH levels,
      indicating that under these conditions the formed complexes are expected to be
      more stable. The findings of the present study were found to be in good agreement
      with the relevant experimental findings where available, thus assessing the role
      of several structural and conformational details in the manifested behavior and
      providing further insight of the effects of non-covalent complexation of PAMAM
      dendrimers with linear poly(ethylene oxide).

PMID- 19865755
TI  - Cavitation activation by dual-frequency ultrasound and shock waves.
AB  - High-speed photographic observations of cavitation occurring under a low
      frequency (21 kHz) sonotrode tip in the presence of an additional, high-frequency
      (355 kHz) ultrasound source have been made in water and in dilute aqueous solute
      solutions. Acoustic emission spectra were measured to support the visual
      observations. It was seen that a nucleating effect of the high-frequency action
      on cavitation at the low-frequency sonotrode was highly power dependent, with
      cavitation being homogenous at low acoustic power and highly localised at high
      acoustic power. The presence of solutes was found to significantly affect the
      cavitation structures and the bubble fragmentation process. Both the fundamental
      high-frequency acoustic emission peak and the higher order low-frequency
      harmonics were significantly intensified in the dual-frequency mode in the
      presence of these solutes. Additionally, the application of a high-voltage
      induced acoustic shock-wave to two different ultrasound fields was investigated
      in water and surfactant solutions.

PMID- 19865756
TI  - The conformational analysis and proton transfer of neuraminidase inhibitors: a
      theoretical study.
AB  - With the aid of density functional calculations, it was revealed that
      neuraminidase (NA) inhibitors (Scheme 1) exist exclusively in the neutral form.
      However, the docking and molecular dynamics simulations indicated that the
      zwitterionic, rather than neutral, isomers are the active form in NA-receptors.
      The neutral and zwitterionic isomers of BA (Compound 7 in Scheme 1) are quite
      different in structure and is therefore expected to show distinct bioactivities.
      With the addition of four water molecules, the geometry of the neutral isomer
      (nBA4) is induced to resemble the zwitterion and remains rather stable throughout
      the proton transfer process (nBA4 --> zBA4); in addition, the energy difference
      between the zwitterionic vs. the neutral isomer is lowered from 24.76 to 2.54
      kcal mol(-1). The zwitterion is the predominant isomer in aqueous solution,
      consistent with the conformational preference in NA-receptors. The proton
      transfer process of nBA4 --> zBA4 is divided into two elementary steps. Step 1,
      rather than step 2, plays a decisive role, owing to the larger energy barrier;
      however, step 1 is not assisted by solvent water, even if it is not water
      suppressed. Accordingly, the proton transfer process that leads to the formation
      of zwitterions is not facilitated in aqueous solution, albeit they may be more
      stable than the neutral isomers. It is thus suggested that the designed antiviral
      inhibitors should be facile to transform into the zwitterionic form in aqueous
      solution. In this way, the oral bioavailability of the antiviral drugs can be
      improved.

PMID- 19865757
TI  - The distortivity of pi-electrons in conjugated boron rings.
AB  - DFT calculations indicate that pi-distortivity in boron rings as manifested via
      the Kekule b(2u) stretching mode is greatly reduced compared to carbocyclic
      annulenes.

PMID- 19865758
TI  - Novel antimonate photocatalysts MSb2O6 (M = Ca, Sr and Ba): a correlation between
      packing factor and photocatalytic activity.
AB  - Well-crystallized MSb(2)O(6) (M = Ca, Sr and Ba) powders synthesized by solid
      state reactions exhibit an interesting photocatalytic activity order of Ba > Sr >
      Ca for organic pollutant (methylene blue and phenol) degradation and hydrogen
      production from water under UV light irradiation. A simple model, crystal packing
      factor (PF), was introduced to account for the activity difference. Nine series
      of photocatalysts involving 26 compounds were experimentally investigated to
      further substantiate the model, a lower PF being correlated to a higher
      photocatalytic activity. This correlation between packing factor and
      photocatalytic activity also holds for some 40 literature examples of 83
      compounds of d(0) cations and d(10) cations. This applicable criterion for
      ranking photocatalytic materials of similar chemistry or structure can be
      rationalized through the influence of structural packing on carrier lifetimes and
      mobilities.

PMID- 19865759
TI  - Modelling fast mode dielectric relaxation of counterions in aqueous solutions of
      ionene bromides and fluorides.
AB  - The parameters derived from previously published (M. Luksicet al.,
      Macromolecules, 2009, 42, 4337-4342) dielectric spectra of aqueous solutions of
      aliphatic 3,3-, 4,5-, 6,6-, and 6,9-ionene bromides and fluorides were analyzed
      within the existing models for the fast counterion-relaxation process. By fitting
      the Poisson-Boltzmann results to the experimental data for the osmotic
      coefficients of the ionenes in question, we were able to estimate the self
      diffusion coefficients of counterions. The coefficients were then used to
      calculate the correlation lengths as proposed by the Ito model. The corresponding
      correlation lengths obtained by the Mandel-Manning model were of similar
      magnitude. The observed trends in correlation lengths were consistent with the
      model-independent values derived from the experimental relaxation times.
      Combination of the dielectric data and Poisson-Boltzmann model analysis yields
      the conclusion that the fluoride counterions prefer longitudinal, whereas the
      bromide counterions favour transverse, fluctuation with respect to the
      polyelectrolyte backbone.

PMID- 19865760
TI  - Real time monitoring of the in situ growth of silver nanoparticles in a polymer
      film under ambient conditions.
AB  - Direct monitoring of the formation and growth of nanoparticles by microscopy in
      real time is of fundamental interest in understanding the chemical and self
      assembly processes involved. Such studies are difficult to implement in solution,
      but have been carried out on solid substrates, mostly under specialized
      conditions, including ultra high vacuum. The present study illustrates the
      facility with which in situ growth of metal nanoparticles in thin polymer films
      under ambient conditions can be monitored by real time atomic force microscopy.
      Formation of silver nanoparticles inside spin-coated thin films of
      poly(vinylpyrrolidone) containing silver nitrate, under ambient conditions, is
      revealed by the emergence and growth of surface plasmon resonance absorption
      extending over several hours. Atomic force microscopy allows 'direct observation'
      of structures growing near the surface; individual nanostructures can be
      monitored in the case of very thin films. A plausible mechanism is proposed for
      the chemical reactions occurring inside the film with the polymer itself acting
      as the reducing agent leading to the formation and growth of the nanoparticles.
      The present study opens up new avenues to carry out investigations into the
      mechanisms and kinetics of nanoparticle growth.

PMID- 19865761
TI  - Formation dynamics of gold nanoparticles in poly(vinylpyrrolidone) and other
      protective agent solutions.
AB  - Intermediate chemical species involved in the formation dynamics of gold
      nanoparticles triggered by photoreduction were detected on the temporal range
      from microseconds to seconds by the near-field heterodyne transient grating
      method. In the dynamic processes, it was found that not only the ionic species of
      gold (H[Au(I)Cl(2)], H[Au(III)Cl(4)]), but also the ionic species that formed
      complex species with the protective agent poly(vinylpyrrolidone) (PVP),
      (H[Au(I)Cl(2)]-PVP, H[Au(III)Cl(4)]-PVP), were involved. In addition, another
      chemical species was observed at PVP concentrations greater than 0.4 mM with the
      HAuCl(4) concentration of 10 mM; its diffusion coefficient was two orders smaller
      than those for the other ionic species. From the reaction mechanism and the
      hydrodynamic diameter for the component (3.5 nm) estimated by the Einstein-Stokes
      equation, we concluded that this component corresponds to gold nanoparticle
      nuclei. Since the dependence of the nuclei concentration on the PVP concentration
      showed a similar dependence as those for the H[Au(I)Cl(2)]-PVP and
      H[Au(III)Cl(4)]-PVP complex species, nucleation of gold nanoparticles occurred by
      way of the complex species. This reaction mechanism is true for the other four
      protecting agents (PVP K15, Triton X-100, Tween 20, Brij 58). Furthermore, we
      investigated the determining factor for the nucleation, and it was clarified that
      the determining factor for nuclei formation is the molecular ratio between
      HAuCl(4) and the protective agent, not the concentration of HAuCl(4) itself.
      Assuming a 2-step mechanism, this result suggests that the reaction is controlled
      by an initial reduction process aided by the protective agents, after which
      growth of the nuclei proceeds.

PMID- 19865762
TI  - In situ diffuse reflectance infrared Fourier transform spectroscopy of MCM-41
      mesoporous silica: mechanistic consideration on the chemical fixation of CO2 with
      N,N'-dimethylethylenediamine to 1,3-dimethyl-2-imidazolidinone.
AB  - In situ diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy has
      been applied to evaluate the thermally activated MCM-41 mesoporous silica as a
      catalyst for CO(2) chemical fixation using N,N'-dimethylethylenediamine (DMEDA),
      and to elucidate the adsorption states of DMEDA, CO(2) and H(2)O on the activated
      silica surface at room temperature or 300 degrees C and at a pressure close to
      the atmospheric one. The thermal activation at 500 degrees C under a flow of dry
      air led to a slight loss of the hydrogen-bonded vicinal and a part of geminal
      silanols as well as physically adsorbed water, whereas the free isolated and most
      of the geminal silanols were not influenced, possibly due to the absence of
      neighboring silanols for condensation to form water and the unfavorable
      dehydration of geminal silanols. Respective adsorptions of Lewis acidic CO(2) and
      basic DMEDA revealed that the free silanols are rather basic, whereas the
      hydrogen-bonded silanols act as Bronsted acid sites. Treatment of the activated
      silica with a CO(2) flow containing DMEDA at 300 degrees C revealed that the
      diamine does not form the corresponding DMEDA-CO(2) adducts such as carbamic
      acids and carbamic acid salts under sufficiently CO(2)-diluted conditions. In
      addition, DMEDA was virtually unable to interact with the silanols under these
      conditions, due to the severe constraints imposed on these silanols by the
      surrounding dense CO(2) molecules. Based on these results, two plausible
      mechanisms were proposed for the CO(2) chemical fixation with DMEDA to 1,3
      dimethyl-2-imidazolidinone (DMI): one involves the reaction of free DMEDA with
      the adsorbed CO(2) interacting with the surface silanols, while the other
      involves the formation of a cyclic carbamic acid salt which subsequently
      undergoes dehydration over the silica to give DMI. Finally, the spectroscopy
      revealed that H(2)O, a byproduct of the DMI formation, is smoothly extracted from
      the surface at 300 degrees C under gaseous CO(2) flow, and does not influence the
      parent surface structure of the silica under the conditions applied.

PMID- 19865763
TI  - Electrochemical hole injection into the valence band of thiol stabilised CdTe
      quantum dots.
AB  - The electrochemical injection of holes into the valence band of mercaptopropionic
      acid stabilised CdTe quantum dots in aqueous solution was investigated employing
      a glassy carbon rotating disc electrode. Analysis of the first exciton peak and
      the electrochemical responses as a function of the particle size was performed
      within the framework of the effective mass approximation and tight-binding
      models. It is demonstrated that the energy of the quantum dot band edges can be
      predicted from capacitance data of bulk semiconductor electrodes modified by the
      same stabilising groups as on the dots. In this paper we show that the thiol
      binding shifts the band edges of the CdTe particles by approximately 0.7 eV with
      respect to the theoretical value in the absence of stabilising groups. The
      results also revealed a significant dependence of the hole-injection rate on the
      electrochemical potential.

PMID- 19865764
TI  - Understanding the physico-chemical properties of polyhedral oligomeric
      silsesquioxanes: a variable temperature multidisciplinary study.
AB  - This work is focused on a multidisciplinary study of a completely condensed
      octaisobutyl-silsesquioxane (IBUPOSS) as a model of the alkyl POSS family.
      IBUPOSS is characterized by the presence of eight isobutyl groups bonded to the
      corners of the siliceous framework. Differential scanning calorimetric
      measurements and an innovative simultaneous in situ Raman/XRPD experiment
      suggested that IBUPOSS undergoes a solid phase transition around 330 K, and
      indicated that this transition is related to a change in the conformational
      freedom of the isobutyl chains. The X-ray powder diffraction (XRPD) pattern of
      the high temperature phase was indexed in the high symmetry [R3m] space group.
      The Raman data indicated a larger mobility of the aliphatic side chains at high
      temperature, thus inducing a disorder in the IBUPOSS moiety. Multidimensional
      heteronuclear solid-state NMR experiments were employed to probe the structural
      and motional features of the observed phase transition. The various conformations
      can be accounted for by a pseudo-D(3h) symmetry able to obey to the [R3m] space
      group. Simulations on molecular mechanics and dynamics, together with quantum
      chemical calculations, confirmed this hypothesis and gave some hints on the
      conformational mobility and the energetic features of IBUPOSS, a base material
      with relevant applications in catalysis and polymer science.

PMID- 19865765
TI  - Morphology hypothesized to influence aerosol particle deliquescence.
AB  - The deliquescence phase transitions of populations of internally mixed particles
      of solid ammonium bisulfate and letovicite, having overall extents of
      neutralization between 0.60 and 0.75 and diameters between 15 and 60 nm, were
      studied using a hygroscopic tandem nano-differential mobility analyzer (HTnDMA).
      Populations having particles sufficiently small or large, as well as particles
      sufficiently acidic or neutralized, behaved as expected, with prompt transitions
      of all particles at a single relative humidity. Populations having particles of
      simultaneously intermediate diameter and acidity, however, behaved differently
      and unexpectedly. Subpopulations of individual particles did exhibit prompt
      deliquescence but did so over a broad range of relative humidity (RH) for the
      entire population. For example, some particles of 20-nm diameter and an extent of
      neutralization of 0.65 deliquesced promptly at as low as 38% RH, whereas some
      particles in the same experiment deliquesced promptly at as high as 59% RH.
      Across this 21% RH span, prompt deliquescence of particle subpopulations was
      observed, which resulted in the continuous deliquescence of the population as the
      aerosol progressed from dominantly solid to dominantly aqueous particles for
      increasing RH. Morphological differences among particles in different
      subpopulations that drive variable rates of water uptake, such as coatings of
      letovicite of varying thickness, porosity, and hence water permeability on cores
      of ammonium bisulfate, are hypothesized to explain these observations.

PMID- 19865766
TI  - Electronic structure models of oxygen adsorption at the solvated, electrified
      Pt(111) interface.
AB  - The adsorption of molecular oxygen is the first step in the oxygen reduction
      reaction. Influences of interfacial water structure and electrode potential on
      oxygen adsorption to the Pt(111) surface were evaluated using density functional
      theory. Two approaches were used to model the electrification of the interface,
      an applied homogeneous electric field and the double-reference method of Filhol,
      Taylor, and Neurock. The free energy change for molecular oxygen replacement of
      water at the surface shows qualitatively different trends between the two models.
      The inclusion of solvation effects and direct control of the electrode potential
      offered by the double-reference method lead to the conclusion that O(2)
      replacement of water is favorable at all potentials studied, and O(2) binding
      becomes more favorable with increasing potential. This trend is contrary to that
      observed using an external electric field model to represent the electrochemical
      double layer, and arises due to the compounded effect of potential on water
      surface, oxygen-surface, and water-molecular oxygen interactions. These results
      indicate that oxygen replacement of adsorbed water does not limit the overall
      oxygen reduction reaction rate at a proton-exchange membrane fuel cell cathode.
      The impacts of aspects of model construction (number of water layers, water
      density) and variation of electrode potential on the O(2)-Pt(111) interaction are
      described.

PMID- 19865767
TI  - The detection and control of stable and transient acoustic cavitation bubbles.
AB  - Acoustic cavitation plays a significant role in many applications that include
      therapeutic medicine, sonochemsitry and materials processing. The type of
      cavitation bubbles generated, namely transient or stable (repetitive transient),
      is important for optimizing the efficiency of these applications. We report on a
      multibubble sonoluminescence (MBSL)-based experimental technique for the
      detection and the control of type of cavitation at low and high ultrasound
      frequencies. It is observed that the use of a horn-type sonicator operating at 20
      kHz primarily generates transient cavitation bubbles, as reported earlier.
      However, the use of plate type transducers at low frequencies (25 and 37 kHz)
      generates a significant amount of stable cavitation, as evidenced from the
      quenching of sonoluminescence by volatile solutes. Evidence for the existence of
      transient cavitation at a higher ultrasound frequency (440 kHz) is also provided.

PMID- 19865768
TI  - Mechanism of molecular hydrogen dissociation on gold chains and clusters as model
      prototypes of nanostructures.
AB  - The reactivity of H(2) on several gold clusters is studied using density
      functional theory with generalized gradient approximation methods, as model
      systems designed to study the main effects determining their catalytic properties
      under controlled conditions. Border effects are studied in finite linear gold
      chains of increasing size and compared with the corresponding periodic systems.
      In these linear chains, the reaction can proceed with no barrier along the
      minimum energy path, presenting a deep chemisorption well of approximately 1.4
      eV. The mechanism presents an important dependence on the initial attacking site
      of the chain. Linear Au(4) chains joined to model-nanocontacts, formed by 2 or 3
      gold atoms, in a planar triangle or in a pyramid, respectively, are also studied.
      The reaction barriers found in these two cases are approximately 0.24 and 0.16
      eV, respectively, corresponding to H(2) attacking the more coordinated edge atom
      of the linear chain. The study is extended to planar clusters with coordinations
      IV and VI, for which higher H(2) dissociation barriers are found. However, when
      the planar gold clusters are folded, and the Au-Au distances elongated, the
      reactivity increases considerably. This is not due to a change of coordination,
      but to a larger flexibility of the gold orbitals to form bonds with hydrogen
      atoms, when the planar sd-hybridization is broken. Finally, it is concluded that
      the major factor determining the reactivity of gold clusters is not strictly the
      coordination of gold atoms but their binding structure and some border effects.

PMID- 19865769
TI  - Adsorption behavior of salicylic, benzoic, and 2-methyl-2-hexenoic acid on
      alumina: an in situ modulation excitation PM-IRRAS study.
AB  - Adsorption and desorption of acid molecules (10(-4) M in cyclohexane) with
      different functional groups, namely salicylic acid (SA), benzoic acid (BA) and 2
      methyl-2-hexenoic acid (MHA), on an Al(2)O(3) thin film was studied by in situ
      polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS).
      We used a flow-through PM-IRRAS cell to induce adsorption and desorption
      processes by alternating acid concentration. Simultaneous but separate detection
      of liquid-phase and surface species was achieved in a time-resolved manner by PM
      IRRAS providing insight into the adsorption-desorption behavior and their
      kinetics. The reliability and sensitivity of recorded surface and liquid-phase
      spectra were assured by comparative measurements using attenuated total
      reflection infrared spectroscopy (ATR-IRS) and density functional theory (DFT)
      calculations. All three acids irreversibly adsorbed on the basic alumina sites in
      a bridging mode. Remarkably, reversibly adsorbing surface species were only
      detected for SA, whereas BA and MHA adsorption were irreversible. To enhance the
      sensitivity and to obtain kinetic information on adsorption and desorption
      processes, PM-IRRAS was combined with modulation excitation spectroscopy (MES)
      applying periodic acid concentration changes. The MES experiments revealed
      distinct kinetic responses of liquid-phase SA and two different types of surface
      adsorbed SA species. One of the adsorbed SA was a dimer-like species loosely
      bound to the alumina surface and the other was probably strongly bound and
      interacting with other adsorbed SA molecules by hydrogen-bonding. The formation
      of the two surface species was induced by the presence of the hydroxyl group in
      SA which most likely enhances the intermolecular interaction via hydrogen-bonding
      near and on the alumina surface.

PMID- 19865770
TI  - Orientation of the GM1 ganglioside in Langmuir-Blodgett monolayers: a PM IRRAS
      and computational study.
AB  - The GM1 ganglioside in the monolayer at the air/water interface shows a liquid
      expanded-liquid condensed phase transition. Due to a combination of the PM IRRAS
      results with quantum chemical calculations the structure and orientation of the
      GM1 molecule in the monolayer on the sub-molecular level is provided. The PM
      IRRAS studies of GM1 monolayers demonstrate that the phase transition is
      accompanied by a reorientation of sugar residues with simultaneous changes in the
      network of hydrogen bonds. The calculation of the IR spectrum of the GM1 molecule
      allowed us to describe individual nu(as)(COC) modes in sugar residues of the GM1
      pentasaccharide. The visualization of the dipole moment vector of each analyzed
      nu(as)(COC) band allowed us to discuss the orientation of the polar head group of
      the GM1 in the monolayer. In the liquid expanded state the planes of two sugar
      residues: beta-Gal-(1-3)-betaGlc-(1-1)-Cer of the GM1 molecule are tilted by ca.
      55 degrees with respect to the surface normal. The plane of the beta1,4-GalNAc
      sugar ring is inclined by 70 degrees towards the gold surface. The phase
      transition to the liquid condensed state causes simultaneous reduction (by
      approximately 10 degrees) of the tilt of planes of sugar residues. The plane of
      the alpha2,3-Nue5Ac residue (sialic acid) has a nearly perpendicular orientation
      to the gold surface. Upon the transition to the liquid condensed state the
      strength of hydrogen bonds formed by the carboxylate group in the alpha2,3-Nue5Ac
      residue decreases. In parallel, the strength of hydrogen bonds formed by N atoms
      of amide groups of the GM1 molecule increases. These events may be explained by
      loosening and/or breaking of hydrogen bonds between the carboxylate and hydroxyl
      groups in the alpha2,3-Nue5Ac residue in a densely packed monolayer, due to
      steric hindrances. The ceramide group coupling the polar head group with the
      hydrophobic hydrocarbon chains, forms strong hydrogen bonds. The C=O bond of the
      amide group is almost perpendicular to the gold surface orientation. The
      hydrocarbon chains of the GM1 exist in a liquid disordered state and their
      physical state and orientation are not affected by the phase transition.

PMID- 19865771
TI  - Diffusion-mediated resonant energy transfer in lanthanide-based polymer white
      light-emitting diodes.
AB  - We present a single layer, polymer white light emitting diode (WOLED) based on
      novel organic lanthanide complexes. The device is solution processed and
      possesses CIE coordinates of (0.33, 0.38), corresponding to a high color purity
      white light emission. The electroluminescence in this diode is found to originate
      from both the direct charge trapping on the lanthanide complexes and from the
      efficient diffusion-assisted long-range energy transfer between the conductive
      matrix and these emissive dopants. An expression for the steady-state transfer
      efficiency is given, the role of excitation diffusion in the system under study
      is quantitatively evaluated, and the values for the singlet exciton diffusion
      coefficients and diffusion lengths in the host are determined.

PMID- 19865772
TI  - Product vibrational distributions in polyatomic species based on quasiclassical
      trajectory calculations.
AB  - By including anharmonicity and Coriolis coupling terms, we have improved our
      earlier quasi-classical method for vibrational mode analysis in polyatomic
      species, which was based on a harmonic approach. Because accurate methods have
      been developed only for diatomic and triatomic systems, the new algorithm was
      tested against accurate methods for diatomic molecules, and against the
      semiclassical fast Fourier transform (FFT) method for triatomic species, finding
      excellent agreement. The new algorithm is designed to be used with dynamics
      studies based on quasi-classical trajectory (QCT) calculations, and it is general
      for any polyatomic species.

PMID- 19865773
TI  - Photophysics of xanthine: computational study of the radiationless decay
      mechanisms.
AB  - A comprehensive investigation of the (1)pi pi*, (1)n pi* and (1)pi sigma* excited
      states of xanthine has been performed with the CASSCF, CASPT2, CC2 and ADC(2)
      methods. The 7H-diketo and 9H-diketo tautomers of xanthine, which are the lowest
      energy tautomers in the ground state, have been studied. Out-of-plane deformation
      of the purine system in the lowest (1)pi pi* state as well as dissociation of the
      NH bonds in the lowest (1)pi sigma* state have been considered. Several conical
      intersections between the (1)pi pi* and S(0) energy surfaces have been located.
      It has been found that the out-of-plane deformation occurs in the five-membered
      ring. With respect to out-of-plane deformation in the (1)pi pi* state leading to
      the (1)pi pi*-S(0) conical intersections, the 7H-diketo tautomer exhibits lower
      energy barriers than the 9H-diketo tautomer. On the contrary, for NH dissociation
      in the (1)pi sigma* state, the 7H-diketo tautomer exhibits a substantial energy
      barrier, while the decay of the 9H-diketo tautomer is essentially barrierless. On
      the basis of the computational results, we assign the observed R2PI spectrum of
      xanthine to the 7H-diketo tautomer, in agreement with the assignment of Callahan
      et al. (Phys. Chem. Chem. Phys., 2007, 9, 4587-4591).

PMID- 19865774
TI  - Reversible formation of gold nanoparticle-surfactant composite assemblies for the
      preparation of concentrated colloidal solutions.
AB  - We have developed a simple method for the preparation of nearly mono-dispersed
      stable gold colloids with a fairly high concentration using a two step procedure.
      First we synthesize citrate capped gold nanoparticles and then exchange the
      citrate ions with triethyleneglycolmono-11-mercaptoundecylether (EGMUDE). This
      leads to the immediate precipitation and formation of composite assemblies. The
      gold nanoparticles were successfully self-redispersed after a few days. The
      prepared gold colloid can be easily concentrated up to 20 times by separation of
      the flocculated part. UV-visible spectra, transmission electron microscopy (TEM),
      and dynamic light scattering (DLS) were used to characterize the products thus
      formed.

PMID- 19865775
TI  - Model-independent determination of the carrier multiplication time constant in
      CdSe nanocrystals.
AB  - The experimental determination of the carrier multiplication (CM) time constant
      is complicated by the fact that this process occurs within the initial few
      hundreds of femtoseconds after excitation and, in transient-absorption
      experiments, cannot be separated from the buildup time of the 1p-state
      population. This work provides an accurate theoretical determination of the
      electron relaxation lifetime during the last stage of the p-state buildup, in
      CdSe nanocrystals, in the presence of a single photogenerated hole (no CM) and of
      a hole plus an additional electron-hole pair (following CM). From the invariance
      of the 1p buildup time observed experimentally for excitations above and below
      the CM threshold producing hot carriers with the same average per-exciton excess
      energy, and the calculated corresponding variations in the electron decay time in
      the two cases, an estimate is obtained for the carrier multiplication time
      constant. Unlike previous estimates reported in the literature so far, this
      result is model-independent, i.e., is obtained without making any assumption on
      the nature of the mechanism governing carrier multiplication. It is then compared
      with the time constant calculated, as a function of the excitation energy,
      assuming an impact-ionization-like process for carrier multiplication (DCM). The
      two results are in good agreement and show that carrier multiplication can occur
      on timescales of the order of tens of femtoseconds at energies close to the
      observed onset. These findings, which are compatible with the fastest lifetime
      estimated experimentally, confirm the suitability of the impact-ionization model
      to explain carrier multiplication in CdSe nanocrystals.

PMID- 19865776
TI  - Raman scattering of molecular graphenes.
AB  - A simplified theoretical approach for modeling the off-resonance Raman scattering
      of molecular models of confined graphene (polycyclic aromatic hydrocarbons, PAHs)
      is presented and compared with the results from density functional theory
      calculations. This theoretical analysis not only allows for a quick estimate of
      the Raman scattering activity, but also correlates the Raman response to simple
      quantities directly linked to the molecular electronic structure. Owing to its
      simplicity and computational convenience the model can be applied to extended
      graphitic systems. The results of the Huckel calculations of the off-resonance
      Raman bond polarizability parameters of nanometer sized armchair and zizgag
      graphene flakes are shown.

PMID- 19865777
TI  - Non-bonded force field for the interaction between metals and organic molecules:
      a case study of olefins on aluminum.
AB  - In this work, we parameterize an empirical potential for the interaction between
      organic molecules and metal surfaces via force matching. This is done by pursuing
      a self-consistent approach similar to the ones used for equilibrium simulations;
      however, special attention is paid to the suitability of the resulting potential
      for tribological (non-equilibrium) situations. Specifically, we study olefin
      molecules confined between two aluminum surfaces under realistic pressures and
      shear rates. We find that the Buckingham potential produces better agreement with
      the first principle data than other force fields. While our training set only
      contains hexene molecules, we find that the standard error in the fitted olefin
      aluminum interaction increases only by a factor of 1.15 when the force field is
      applied to butene, octene, and decene. Including mirror charges into the
      treatment only marginally improves fits. While olefins on aluminum is merely a
      special case, the proposed methodology can be used to parameterize any other
      interaction between polymers and metal surfaces for use in tribological
      simulations.

PMID- 19865778
TI  - Influence of cyclic polyamines on silica formation during the Stober process.
AB  - The interactions of cyclic polyamines with tetraethoxysilane in the conditions of
      the Stober synthesis of silica nanoparticles were studied and compared to the
      behavior of a linear polyamine. Granular core-plain shell hybrid particles were
      obtained whose morphology and size vary with the nature and amount of added
      ligand. The influence of polyamines on silica condensation could be understood on
      the basis of a SN(2) reaction involving a pentacoordinated Si complex and depends
      on the accessibility and nucleophilicity of the ligand. In this case, the
      polyamine conformation is the key factor determining its ability to activate
      silica formation. The final size of the hybrid particles was determined by the
      aggregation of resulting primary nanoparticles that is controlled by
      electrostatic interactions, and thus depends on the ligand positive charge. These
      results were compared to biological and biomimetic processes of silica formation
      where acid-base/electrostatic interactions of silica precursors with linear
      polyamines have been described.

PMID- 19865779
TI  - Size effects of aromatic substitution in the ortho position on the
      photodimerization kinetics of alpha-trans cinnamic acid derivatives. A solid
      state NMR study.
AB  - The photoreaction of two alpha-cinnamic acid derivatives, alpha-o-methoxy and
      alpha-o-ethoxy cinnamic acid, was studied by (13)C CPMAS solid-state NMR
      spectroscopy in order to elucidate effects of aromatic substitution and
      substituent size on the kinetics of the [2+2] photodimerization. The reactants
      and products can be clearly differentiated and a detailed spectroscopic
      characterization was carried out, including 2D PASS spectra, at a low spinning
      frequency to determine the principal values of the chemical shift tensor. Density
      functional theory (DFT) calculations of chemical shifts and chemical shift
      anisotropy tensors were found to be in good agreement with the experimental
      results and helped in the individual assignments of reactant and photoproduct
      carbon atoms. The photoreaction kinetics show no systematic variation with
      substituent size, in that the alpha-o-methoxy cinnamic acid progresses at a
      slower rate than unsubstituted alpha-cinnamic acid, but alpha-o-ethoxy cinnamic
      acid at a faster one. Interestingly, the distance between reacting double bonds
      is not a good indicator of photoreaction rate. The observed trend is in part due
      to a larger degree of reorientation of the aromatic ring for the o-methoxy
      cinnamic acid, and a more dominant interaction appears to be the p-orbital
      overlap between two reacting double bonds in determining the reaction kinetics.

PMID- 19865780
TI  - Electronic properties of pentacoordinated heme complexes in cytochrome P450
      enzymes: search for an Fe(I) oxidation state.
AB  - The cytochrome P450s are versatile enzymes that catalyze a range of
      monoxygenation reactions. Their catalytic cycle includes molecular oxygen binding
      and two reduction and protonation steps to create the active species, Compound I.
      In an anaerobic environment, however, only two reduction steps starting from the
      resting state can take place. Currently, very little information is known on this
      doubly-reduced species; therefore, we have performed a detailed density
      functional theory (DFT) and combined quantum mechanics/molecular mechanics
      (QM/MM) study on this complex. In principle, the doubly-reduced pentacoordinated
      heme can exist in two possible electronic configurations, namely an Fe(I) with
      closed-shell heme or an Fe(II) coupled to a heme anion radical [Fe(II) Por(-*)].
      Our calculations show that there are several close-lying spin states with a
      [Fe(II) Por(-*)] configuration and these states are much lower in energy than the
      alternative [Fe(I) Por(0)] situation. We have calculated spectroscopic parameters
      of the lowest lying sextet spin state, including IR spectra and EPR parameters.

PMID- 19865782
TI  - Inadequate dietary intake of children and adolescents with juvenile idiopathic
      arthritis and systemic lupus erythematosus.
AB  - OBJECTIVES: To evaluate the dietary intake of children and adolescents with
      juvenile idiopathic arthritis (JIA) and juvenile systemic lupus erythematosus
      (JSLE) using a 24-hour diet recall and relating it to the patients' clinical and
      anthropometric characteristics and to the drugs used in their treatment. METHODS:
      By means of a cross-sectional study, we assessed the 24-hour diet recalls of
      outpatients. Their nutritional status was classified according to the CDC (2000).
      The computer program NutWin UNIFESP-EPM was used for food intake calculation. The
      Recommended Dietary Allowances and the Brazilian food pyramid were used for
      quantitative and qualitative analysis. RESULTS: Median age was 12 years for JIA
      patients and 16.5 years for JSLE patients. Among the JIA patients, 37.5% had
      active disease, and among the JSLE patients, 68.2% showed Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI) > 4. Malnutrition was found in 8.3
      and 4.5% of the JIA and JSLE patients, respectively, and obesity was present in
      16.7 and 18.2%. For JIA patients, the excessive intake of energy, protein, and
      lipids was 12.5, 75, and 31.3%, respectively. For JSLE patients, the excessive
      intake of energy, protein, and lipids was 13.6, 86.4, and 36.4%, respectively.
      Low intake of iron, zinc, and vitamin A was found in 29.2 and 50, 87.5 and 86.4,
      and 87.5 and 95.2% of the JIA and JSLE patients, respectively. There was not a
      significant association between intake, disease activity, and nutritional status.
      CONCLUSION: Patients with rheumatic diseases have inadequate dietary intake.
      There is excessive intake of lipids and proteins and low intake of
      micronutrients.

PMID- 19865783
TI  - Overactive bladder: a new paradigm.

PMID- 19865784
TI  - Molecular variation in neuropeptide Y and bone mineral density among men of
      African ancestry.
AB  - Neuropeptide Y (NPY) is a physiological candidate gene for the regulation of body
      weight and has more recently been implicated in regulating bone mass. The current
      study sought to test if inherited variation in NPY might influence BMD in a
      population of African-ancestry men who have high bone mineral density (BMD). We
      genotyped 17 tagging single-nucleotide polymorphisms (SNPs) across the NPY gene
      region in 1,113 randomly selected men of African ancestry aged >or=40 years and
      tested for association with anthropometric characteristics and proximal femur
      BMD. The homozygous rare genotype of four SNPs was associated with a 0.92-1.59%
      decrease in stature (corrected P < 0.05). No SNP was associated with body mass
      index or body weight. Two SNPs in a 5-kb linkage disequilibrium block
      encompassing exons 3 and 4 were associated with proximal femur BMD, adjusted for
      age, body weight, and height (corrected P < 0.05). These results suggest that
      genetic variation at the NPY locus may contribute to bone density, independently
      of body weight.

PMID- 19865785
TI  - FXYD2 and Na,K-ATPase expression in isolated human proximal tubular cells:
      disturbed upregulation on renal hypomagnesemia?
AB  - Autosomal dominant renal hypomagnesemia (OMIM 154020), associated with
      hypocalciuria, has been linked to a 121G to A mutation in the FXYD2 gene. To gain
      insight into the molecular mechanisms linking this mutation to the clinical
      phenotype, we studied isolated proximal tubular cells from urine of a patient and
      a healthy subject. Cells were immortalized and used to assess the effects of
      hypertonicity-induced overexpression of FXYD2 on amount, activity and apparent
      affinities for Na(+), K(+) and ATP of Na,K-ATPase. Both cell lines expressed mRNA
      for FXYD2a and FXYD2b, and patient cells contained both the wild-type and mutated
      codons. FXYD2 protein expression was lower in patient cells and could be
      increased in both cell lines upon culturing in hyperosmotic medium but to a
      lesser extent in patient cells. Similarly, hyperosmotic culturing increased Na,K
      ATPase protein expression and ATP hydrolyzing activity but, again, to a lesser
      extent in patient cells. Apparent affinities of Na,K-ATPase for Na(+), K(+) and
      ATP did not differ between patient and control cells or after hyperosmotic
      induction. We conclude that human proximal tubular cells respond to a
      hyperosmotic challenge with an increase in FXYD2 and Na,K-ATPase protein
      expression, though to a smaller absolute extent in patient cells.

PMID- 19865786
TI  - Minimum membrane bending energies of fusion pores.
AB  - Membranes fuse by forming highly curved intermediates, culminating in structures
      described as fusion pores. These hourglass-like figures that join two fusing
      membranes have high bending energies, which can be estimated using continuum
      elasticity models. Fusion pore bending energies depend strongly on shape, and the
      present study developed a method for determining the shape that minimizes bending
      energy. This was first applied to a fusion pore modeled as a single surface and
      then extended to a more realistic model treating a bilayer as two monolayers. For
      the two-monolayer model, fusion pores were found to have metastable states with
      energy minima at particular values of the pore diameter and bilayer separation.
      Fusion pore energies were relatively insensitive to membrane thickness but highly
      sensitive to spontaneous curvature and membrane asymmetry. With symmetrical
      bilayers and monolayer spontaneous curvatures of -0.1 nm(-1) (a typical value)
      separated by 6 nm (closest distance determined by repulsive hydration forces),
      fusion pore formation required 43-65 kT. The pore radius of approximately 2.25 nm
      fell within the range estimated from conductance measurements. With bilayer
      separation >6 nm, fusion pore formation required less energy, suggesting that
      protein scaffolds can promote fusion by bending membranes toward one another.
      With nonzero spontaneous monolayer curvature, the shape that minimized the energy
      change during fusion pore formation differed from the shape that minimized its
      energy after it formed. Thus, a nascent fusion pore will relax spontaneously to a
      new shape, consistent with the experimentally observed expansion of nascent
      fusion pores during viral fusion.

PMID- 19865788
TI  - PKA mediates constitutive activation of CFTR in human sweat duct.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels are
      constitutively activated in sweat ducts. Since phosphorylation-dependent and 
      independent mechanisms can activate CFTR, we sought to determine the actual
      mechanism responsible for constitutive activation of these channels in vivo. We
      show that the constitutively activated CFTR Cl(-) conductance (gCFTR) in the
      apical membrane is completely deactivated following alpha-toxin permeabilization
      of the basolateral membrane. We investigated whether such inhibition of gCFTR
      following permeabilization is due to the loss of cytoplasmic glutamate or due to
      dephosphorylation of CFTR by an endogenous phosphatase in the absence of kinase
      activity (due to the loss of kinase agonist cAMP, cGMP or GTP through alpha-toxin
      pores). In order to distinguish between these two possibilities, we examined the
      effect of inhibiting the endogenous phosphatase activity with okadaic acid (10(
      8) M) on the permeabilization-induced deactivation of gCFTR. We show that okadaic
      acid (1) inhibits an endogenous phosphatase responsible for dephosphorylating
      cAMP but not cGMP or G protein-activated CFTR and (2) prevents deactivation of
      CFTR following permeabilization of the basolateral membrane. These results
      indicate that distinctly different phosphatases may be responsible for
      dephosphorylating different kinase-specific sites on CFTR. We conclude that the
      phosphorylation by PKA alone appears to be primarily responsible for constitutive
      activation of gCFTR in vivo.

PMID- 19865787
TI  - Role of calcineurin-mediated dephosphorylation in modulation of an inwardly
      rectifying K+ channel in human proximal tubule cells.
AB  - Activity of an inwardly rectifying K(+) channel with inward conductance of about
      40 pS in cultured human renal proximal tubule epithelial cells (RPTECs) is
      regulated at least in part by protein phosphorylation and dephosphorylation. In
      this study, we examined involvement of calcineurin (CaN), a Ca(2+)/calmodulin
      (CaM)-dependent phosphatase, in modulating K(+) channel activity. In cell
      attached mode of the patch-clamp technique, application of a CaN inhibitor,
      cyclosporin A (CsA, 5 microM) or FK520 (5 microM), significantly suppressed
      channel activity. Intracellular Ca(2+) concentration ([Ca(2+)]( i )) estimated by
      fura-2 imaging was elevated by these inhibitors. Since inhibition of CaN
      attenuates some dephosphorylation with increase in [Ca(2+)]( i ), we speculated
      that inhibiting CaN enhances Ca(2+)-dependent phosphorylation, which might result
      in channel suppression. To verify this hypothesis, we examined effects of
      inhibitors of PKC and Ca(2+)/CaM-dependent protein kinase-II (CaMKII) on CsA
      induced channel suppression. Although the PKC inhibitor GF109203X (500 nM) did
      not influence the CsA-induced channel suppression, the CaMKII inhibitor KN62 (20
      microM) prevented channel suppression, suggesting that the channel suppression
      resulted from CaMKII-dependent processes. Indeed, Western blot analysis showed
      that CsA increased phospho-CaMKII (Thr286), an activated CaMKII in inside-out
      patches, application of CaM (0.6 microM) and CaMKII (0.15 U/ml) to the bath at
      10(-6) M Ca(2+) significantly suppressed channel activity, which was reactivated
      by subsequent application of CaN (800 U/ml). These results suggest that CaN plays
      an important role in supporting K(+) channel activity in RPTECs by preventing
      CaMKII-dependent phosphorylation.

PMID- 19865789
TI  - Rare enlargement of the genial tubercles. Enlargement of genial tubercles.
AB  - Genial tubercles usually are small bony protuberances on the lingual aspect of
      the mandible symphysis. Conversely, this case shows 3D tomographic reconstruction
      images of genial tubercles as an oversized projection causing pain and discomfort
      to the patient.

PMID- 19865790
TI  - Liver functional reserve estimation: state of the art and relevance for local
      treatments: the Eastern perspective.
AB  - Liver function reserve estimation is important for selecting the appropriate
      patients for hepatectomy or ablation of tumors. Many liver function tests have
      been devised, but the indocyanine green (ICG) clearance test remains the most
      popular for its simplicity and perhaps accuracy. Compared with the Child-Pugh
      classification, the ICG retention value at 15 min (ICGR-15) after intravenous
      injection provides more information. Though a significant difference in ICGR-15
      has been observed between patients with Child-Pugh A and B liver function, the
      hospital mortality rates following partial hepatectomy are not significantly
      different between the two groups. Yet, ICGR-15 values can differentiate patients
      with or without hospital mortality. The cutoff values of ICGR-15 for a safe major
      and minor hepatectomy are 14 and 22%, respectively.

PMID- 19865791
TI  - Duodenum-preserving total pancreatectomy for pancreatic neoplasms.
AB  - BACKGROUND/PURPOSE: Total pancreatectomy (TP) is sometimes performed to treat low
      grade malignant neoplasms that are spreading to the entire pancreas. However, TP
      impairs quality of life, due to the resulting loss of pancreatic exocrine and
      endocrine function, and an organ-preserving procedure should be chosen to
      minimize the impact of pancreatic dysfunction. Recently, we performed four
      duodenum-preserving TPs (DPTPs) on patients with low-grade malignant neoplasms of
      the entire pancreas and we introduce our operative technique and results herein.
      METHODS: DPTP is performed with the objective of preserving the arterial arcade
      of the posterior pancreas so as to maintain good blood flow in the duodenum and
      common bile duct. Care must also be taken to preserve the splenic artery and vein
      to protect the spleen. When patients are also undergoing a bile duct resection,
      an end-to-side choledochoduodenostomy is also performed to reconstruct the
      biliary tract. RESULTS: Patient 1: DPTP with preservation of the spleen,
      conserving splenic vessels, was performed on a patient with hereditary pancreatic
      carcinoma with pancreatic intraepithelial neoplasia-3 (PanIN-3). Patient 2: DPTP
      with splenectomy was performed on a patient with multiple metastases of the
      entire pancreas from renal cell carcinoma. Patient 3: DPTP with preservation of
      the common bile duct and the spleen, conserving splenic vessels, was performed on
      a patient with minimally invasive carcinoma derived from intraductal papillary
      mucinous neoplasm (IPMN). Patient 4: DPTP with preservation of the spleen,
      conserving splenic vessels, was performed on a patient with minimally invasive
      carcinoma derived from IPMN. No deaths or morbidity occurred. All patients were
      placed on pancreatic enzyme replacement therapy and given a daily dose of insulin
      of approximately 30 U. Complete professional rehabiliation was achieved in all
      patients. All patients except one gained weight, and the hemoglobin A1c (HbA1c)
      levels have been maintained at around 7%. CONCLUSIONS: DPTP is a useful organ
      preserving procedure for low-grade malignant neoplasms spreading within the
      entire pancreas. This procedure minimizes the impact of pancreatic dysfunction
      and allows the patient to maintain good nutrition after surgery.

PMID- 19865792
TI  - Parenchyma-sparing resections for pancreatic neoplasms.
AB  - BACKGROUND/PURPOSE: In recent years there has been an increase in the indications
      for pancreatic resection of benign or low-grade malignant lesions, especially in
      young patients with long life expectancy. In this setting, patients may benefit
      from parenchyma-sparing resections in order to decrease the risk of development
      of exocrine/endocrine insufficiency. METHODS: A review of the literature and
      authors experience was undertaken. RESULTS: Parenchyma-sparing resections of the
      pancreas including enucleation, middle pancreatectomy (MP) and middle-preserving
      pancreatectomy are described. Short and long-term outcomes after surgery are
      analyzed with special regard to postoperative morbidity/mortality, and
      oncological and functional long-term results. CONCLUSIONS: Parenchyma-sparing
      resections are safe and effective procedures for treatment of benign and low
      grade malignant neoplasms. Despite a significant postoperative morbidity they are
      associated with good long-term functional and oncological results. Enucleation
      should preferentially be performed laparoscopically whenever possible.

PMID- 19865794
TI  - Angiotensin-converting enzyme gene polymorphism is associated with proliferative
      diabetic retinopathy: a meta-analysis.
AB  - The association of angiotensin-converting enzyme (ACE) gene polymorphism with
      diabetic retinopathy (DR) was investigated in many studies with conflicting
      results. To shed light on these inconclusive findings, a meta-analysis of all
      available studies relating I (insert)/D (delete) polymorphism to the risk of
      developing DR was conducted. This meta-analysis included genotype data on 2,342
      cases with DR and 2,048 controls free of DR. Summary odds ratios were estimated.
      Potential sources of heterogeneity and bias were explored. Overall, in allelic
      genetic model, heterogeneity between studies was nonsignificant (P = 0.12). No
      publication bias was observed in the regression asymmetry test (tau = 0.84, P =
      0.41). There was no significant association between this variant and DR. In
      additional analysis, the association of I/D variant with retinopathy was
      nonsignificant both in patients with type 1 diabetes (T1D) (1.01 [95% CI: 0.79
      1.29]) and in patients with type 2 diabetes (T2D) (1.12 [95% CI: 0.93-1.35]).
      Significant association was not also observed between I/D variant and the
      background diabetic retinopathy (BDR). For the I/D polymorphism and its
      relationship to proliferative diabetic retinopathy (PDR), the dominant model
      showed nonsignificant heterogeneity among studies (P = 0.52; I (2) = 0%), and the
      fixed estimate pooled odd ratio (OR) JOP was significant, at 1.37 [95% CI: 1.02
      1.84]. No association was observed between ACE I/D variant and DR, irrespective
      of the diabetic type. There was moderate evidence of its relationship to PDR,
      while its relationship to BDR was not found. Studies exploring the association
      between ACE I/D polymorphism and BDR or PDR may help us better understand the
      genetics of DR.

PMID- 19865795
TI  - A prospective study of hip revision surgery using the Exeter long-stem
      prosthesis: function, subsidence, and complications for 57 patients.
AB  - BACKGROUND: The long-stem Exeter femoral component is commonly used in revision
      hip surgery. Subsidence of the femoral stem in primary hip arthroplasty has been
      studied extensively, but much less is known about its significance in revision
      surgery. This prospective study examined the relationship between radiological
      subsidence, Western Ontario and McMaster (WOMAC) osteoarthritis index pain score,
      patient satisfaction and complication rates for the long-stem Exeter hip
      prosthesis. MATERIALS AND METHODS: Data was prospectively collected for a single
      surgeon series of 96 patients undergoing revision surgery with a mean follow-up
      period of 36 months. Pre- and post-operative clinical evaluation was carried out
      using the validated WOMAC osteoarthritis index. Radiographic evaluation was
      carried out on magnification-adjusted digital radiographic images. RESULTS: Data
      from 57 patients were analysed. The mean rate of subsidence recorded was 0.43
      mm/year, with a mean total subsidence of 0.79 mm [95% confidence interval (CI)
      0.57-1.01] at 36.3 months. There was no correlation between subsidence and post
      operative WOMAC score, complication rate or patient satisfaction. There was a
      statistically significant reduction between pre-operative and post-operative
      WOMAC scores, with means of 33.5 and 10.7, respectively (P < 0.001), and high
      patient satisfaction. CONCLUSION: Our subsidence rates for long-stem revision
      femoral components are lower than the published data but demonstrate the same
      plateau. Radiographic subsidence does not appear to relate to functional outcome
      or complication rates in our data.

PMID- 19865796
TI  - Tumor irrigation fluid enhances diagnostic efficacy  in endoscopic biopsies of
      intracranial space-occupying lesions.
AB  - PURPOSE: Intraventricular neuroendoscopic CNS biopsiesare small, fragmented, and
      tissue is frequently inadequate for diagnosis. We have attempted to increase
      cellular yield using tumor irrigation fluid (TIF) and a cyto-histological
      approach for diagnosis of intracranial tumors, cysts, and infections. METHODS: A
      retrospective group of 147 cases, where only endoscopic biopsies were obtained,
      was compared with a prospective group of 31 cases where along with the endoscopic
      biopsies, tumor irrigation fluid (TIF) was collected. Tumor cyst fluid was
      obtained from cystic tumors (n=6). Small tumor fragments in the TIF were utilized
      to make squash smears (n=31). Clotted fragments were processed for sections in
      (n=3). Centrifuged deposit smears were prepared from tumor irrigation fluid and
      tumor cyst fluid. RESULTS: Conclusive pathological diagnosis in endoscopic
      biopsies could be arrived at in 77.4% (24/31) prospective cases and 80.3%
      (118/147) in retrospective cases. Collection of TIF with a cyto-histological
      diagnostic approach gave a significantly higher rate of conclusive pathological
      diagnosis in 93.5% (29/31) cases in the prospective group. CONCLUSIONS:
      Additional tissue from TIF preserves the original biopsy, provides more material
      for diagnosis and gives a better morphological picture in smears. Hence diagnosis
      of endoscopic CNS biopsies can be rendered in more cases and with greater degree
      of confidence.

PMID- 19865797
TI  - Dependence of 6beta-acetoxy-7alpha-hydroxyroyleanone block of Kv1.2 channels on C
      type inactivation.
AB  - Voltage-gated K(+) (Kv) channels exhibit slow or C-type inactivation during
      continuous depolarization. A selective pharmacological agent targeting C-type
      inactivation is hitherto lacking. Here, we report that 6beta-acetoxy-7alpha
      hydroxyroyleanone (AHR), a diterpenoid compound isolated from Taiwania
      cryptomerioides, can selectively modify C-type inactivation of Kv1.2 channels.
      Extracellular, but not intracellular, AHR (50 muM) dramatically accelerated the
      slow decay of Kv currents and left-shifted the steady-state inactivation curve.
      AHR blocked Kv currents with an IC(50) of 17.7 muM. AHR did not affect the
      kinetics and voltage-dependence of Kv1.2 channel activation. Channel block by AHR
      was independent of intracellular K(+) concentration. In addition, effect of AHR
      was much attenuated in a Kv1.2 V370G mutant defective in C-type inactivation.
      Therefore, block of Kv1.2 channels by AHR did not appear to involve direct
      occlusion of the outer pore but depended on C-type inactivation. AHR could thus
      be a probe targeting Kv channel C-type inactivation gate.

PMID- 19865799
TI  - A coumarin derivative (RKS262) inhibits cell-cycle progression, causes pro
      apoptotic signaling and cytotoxicity in ovarian cancer cells.
AB  - Coumarin derivative RKS262 belongs to a new class of potential anti-tumor agents.
      RKS262 was identified by structural optimization of Nifurtimox which is currently
      undergoing phase II clinical trials to treat high-risk neuroblastoma. In a
      NCI(60) cell-line assay RKS262 exhibited significant cytotoxicity in ovarian
      cancer cells and a variety of other cell lines exceeding effects of commercial
      drugs such as cisplatin, 5-FU, cyclophosphamide or sapacitabine. Various leukemia
      cell-lines were most sensitive (GI(50): ~ 10 nM) while several non-small cell
      lung cancer cell lines and few cell lines from other tissues were relatively
      resistant (GI(50) > 1 uM) to RKS262 treatment. The mechanism of cytotoxicity was
      examined using ovarian cancer cell-line OVCAR-3 as a model. RKS262 treatment
      resulted in a reduced mitochondria-transmembrane-depolarization potential. RKS262
      effects included up-regulation of apoptotic markers and were not correlated with
      activation of pro-apoptotic MAP-Kinases (p38, SAP/JNK). RKS262 exerted strong
      inhibitory effects on oncogene ras, down-regulated DNA-pk KU-80 subunit
      expression and caused activation of Akt. A signature effect of RKS262 is the
      regulation of the mitochondrial Bcl2-family pathway. Pro-apoptotic factors Bid,
      Bad and Bok were up-regulated while expression of pro-survival factors Bcl-xl and
      Mcl-1 was inhibited. Moreover, at sub-cytotoxic doses RKS262 delayed OVCAR-3 cell
      cycle progression through G2 phase and up-regulated p27 while cyclin-D1 and Cdk-6
      were down-regulated, indicating that RKS262 is a specific cyclin/CDK inhibitor.
      In summary, RKS262 has been identified as a molecule belonging to a new class of
      potential chemotherapeutic agents affecting the viability of multiple cancer cell
      lines and causing selective adverse effects on the viability of ovarian cancer
      cells.

PMID- 19865798
TI  - Melanopsin and inner retinal photoreception.
AB  - Over the last ten years there has been growing acceptance that retinal
      photoreception among mammals extends beyond rods and cones to include a small
      number of intrinsically photosensitive retinal ganglion cells (ipRGCs). These
      ipRGCs are capable of responding to light in the absence of rod/cone input thanks
      to expression of an opsin photopigment called melanopsin. They are specialised
      for measuring ambient levels of light (irradiance) for a wide variety of so
      called non-image-forming light responses. These include synchronisation of
      circadian clocks to light:dark cycles and the regulation of pupil size, sleep
      propensity and pineal melatonin production. Here, we provide a review of some of
      the landmark discoveries in this fast developing field, paying particular
      emphasis to recent findings and key areas for future investigation.

PMID- 19865800
TI  - Specific chromosomal imbalances as detected by array CGH in ependymomas in
      association with tumor location, histological subtype and grade.
AB  - Ependymomas are glial neoplasms originating from the wall of the ventricles or
      from the spinal canal. The significance of histopathological features in
      accurately predicting biological behavior is still debated. Moreover, key
      molecular events in the pathogenesis of ependymoma are yet to be defined. The
      main objective of the present study was to identify specific patterns of
      chromosomal aberrations that correlate with tumor location, histological subtype
      and grade. Forty-five ependymoma samples were analyzed by 1-megabase resolution
      array comparative genomic hybridization (CGH). Association between clinical or
      histopathological parameters and the genomic alterations identified was
      evaluated. The most frequently detected chromosome (chr) abnormalities were gain
      of chr 7, 9, 12 and 15 and loss of chr 22. Co-occurrence of those five
      alterations characterized spinal ependymomas (P = 0.01). Myxopapillary
      ependymomas displayed a specific genomic profile defined by concurrent gain of
      chr 5, 7, 9, 16 and 18 (P = 0.0007). Overall, the number of chromosomal
      abnormalities detected was inversely correlated with the malignancy grade. Gain
      of chr 1q correlated with intracranial high-grade tumors (P = 0.002). Loss of chr
      6q was mainly observed in infratentorial (P = 0.02) and World Health Organization
      (WHO) grade III (P = 0.04) lesions. Chr 10q loss was associated with high-grade
      ependymomas (P = 0.01). The +7/+9/+12/+15/-22 genomic profile is significantly
      associated with WHO grade II spinal ependymomas, whereas the +5/+7/+9/+16/+18
      genomic pattern is specific of myxopapillary ependymomas. Identification of
      specific genomic imbalances at a given tumor location suggests that ependymomas
      from different central nervous system (CNS) regions represent genetically
      distinct diseases. Detecting genomic alterations associated with aggressive
      biological behavior may help stratify patients in high- and low-risk disease.

PMID- 19865801
TI  - A tissue-level electromechanical model of the left ventricle: application to the
      analysis of intraventricular pressure.
AB  - The ventricular pressure profile is characteristic of the cardiac contraction
      progress and is useful to evaluate the cardiac performance. In this contribution,
      a tissue-level electromechanical model of the left ventricle is proposed, to
      assist the interpretation of left ventricular pressure waveforms. The left
      ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic
      sub-systems. The asynchronous contraction of these twelve myocardial segments has
      been represented in order to reproduce a realistic pressure profiles. To take
      into account the different energy domains involved, the tissue-level scale and to
      facilitate the building of a modular model, multiple formalisms have been used:
      Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for
      the electrical activation. An experimental protocol has been defined to acquire
      ventricular pressure signals from three pigs, with different afterload
      conditions. Evolutionary Algorithms have been used to identify the model
      parameters in order to minimize the error between experimental and simulated
      ventricular pressure signals. Simulation results show that the model is able to
      reproduce experimental ventricular pressure. In addition, electro-mechanical
      activation times have been determined in the identification process. For example,
      the maximum electrical activation time is reached, respectively, 96.5, 139.3 and
      131.5 ms for the first, second, and third pigs. These preliminary results are
      encouraging for the application of the model on non-invasive data like ECG,
      arterial pressure or myocardial strain.

PMID- 19865802
TI  - Trace elements contents in Asparagus curillus (Buch.-Ham.) ex Roxb.
AB  - Concentration level of nine elements viz. Zn, Cu, Mn, Fe, Co, Na, K, Ca, and Li
      were determined in leaves and roots of Asparagus curillus (Buch.-Ham.) ex Roxb.
      collected from four different altitudes in three seasons by atomic absorption
      spectroscopy. The overall concentration of K was found to be highest, whereas the
      level of Cu was lowest. The maximum concentrations of Zn, Cu, Mn, Fe, Co, Na, K,
      Ca, and Li were found to be 97.0 +/- 1.5, 28.0 +/- 7.0, 44.0 +/- 7.3, 1138.0 +/-
      18.5, 91.0 +/- 6.2, 381.0 +/- 7.8, 9508.0 +/- 7.8, 3076.0 +/- 6.4, and 78.0 +/-
      4.6 mg/kg, respectively.

PMID- 19865803
TI  - Urine iodine levels in preeclamptic and normal pregnant women.
AB  - The aim of this study was to investigate the urine iodine concentration in women
      with severe preeclampsia and in healthy women in Erzurum, Turkey. Urine specimens
      were obtained from 40 severe preeclampsia and 18 healthy pregnant women. Urinary
      iodine levels were determined by the Foss method based on the Sandell-Kolthoff
      reaction. The urinary iodine level for women with severe preeclampsia was 4.25 +/
      2.7 microg/dL, lower than 20.89 +/- 6.4 microg/dL of urinary iodine for healthy
      pregnant women (p < 0.001). Blood magnesium concentration was found to be 1.63 +/
      0.05 mg/dL for women with severe preeclampsia, which is lower than that of
      healthy pregnant women (1.87 +/- 0.05 mg/dL; p < 0.001). There was a positive
      correlation between urinary iodine level and blood magnesium level in pregnant
      women with preeclampsia (Pearson correlation coefficient = 0.43; p < 0.01).
      However, there was no correlation between urinary iodine level and blood
      magnesium level in healthy pregnant women. There was no difference in thyroid
      hormone levels (T4, TSH, FT4) between women with severe preeclampsia and healthy
      pregnant women. However, there was a difference in T3 thyroid hormone levels
      between women with severe preeclampsia (1.86 +/- 0.4 microg/dL) and healthy
      pregnant women (1.45 +/- 0.3 microg/dL; p < 0.001). There was also a difference
      in FT3 between women with severe preeclampsia (2.77 +/- 0.4 pg/mL) and healthy
      pregnant women (2.41 +/- 0.5 microg/dL; p < 0.01). Urinary iodine excretion is
      currently the most convenient laboratory marker of iodine deficiency. The method
      is useful for the rapid and low-cost assessment of iodine deficiency. Our results
      suggested that urinary iodine concentration might be a useful marker for
      prediagnosing preeclamptic women. In addition, iodine supplementation may also be
      considered for preeclamptic therapy.

PMID- 19865804
TI  - Hybrid maize breeding with doubled haploids: V. Selection strategies for
      testcross performance with variable sizes of crosses and S(1) families.
AB  - In hybrid maize (Zea mays L.) breeding, doubled haploids (DH) are increasingly
      replacing inbreds developed by recurrent selfing. Doubled haploids may be
      developed directly from S(0) plants in the parental cross or via S(1) families.
      In both these breeding schemes, we examined 2 two-stage selecting strategies,
      i.e., considering or ignoring cross and family structure while selection among
      and within parental crosses and S(1) families. We examined the optimum allocation
      of resources to maximize the selection gain DeltaG and the probability P(q) of
      identifying the q% best genotypes. Our specific objectives were to (1) determine
      the optimum number and size of crosses and S(1) families, as well as the optimum
      number of test environments and (2) identify the superior selection strategy.
      Selection was based on the evaluation of testcross progenies of (1) DH lines in
      both stages (DHTC) and (2) S(1) families in the first stage and of DH lines
      within S(1) families in the second stage (S(1)TC-DHTC) with uniform and variable
      sizes of crosses and S(1) families. We developed and employed simulation programs
      for selection with variable sizes of crosses and S(1) families within crosses.
      The breeding schemes and selection strategies showed similar relative efficiency
      for both optimization criteria DeltaG and P (0.1%). As compared with DHTC, S(1)TC
      DHTC had larger DeltaG and P (0.1%), but a higher standard deviation of DeltaG.
      The superiority of S(1)TC-DHTC was increased when the selection was done among
      all DH lines ignoring their cross and family structure and using variable sizes
      of crosses and S(1) families. In DHTC, the best selection strategy was to ignore
      cross structures and use uniform size of crosses.

PMID- 19865805
TI  - Identification of genetic factors influencing salt stress tolerance in white
      clover (Trifolium repens L.) by QTL analysis.
AB  - Allotetraploid (2n = 4x = 32) white clover (Trifolium repens L.) is the most
      commonly cultivated legume component of temperate pastures, sown in swards with a
      companion grass species. Genetic control of growth performance of white clover on
      saline land is highly important for dairy industries, due to increasing soil
      salinity problems. The objective of this study was to identify quantitative trait
      loci (QTLs) for salinity tolerance in terms of vegetative growth under stress.
      Two parental genetic maps consisting of 213 and 159 marker loci and spanning
      1,973.0 and 1,837.6 cM, respectively, were constructed using simple sequence
      repeat (SSR) and single nucleotide polymorphism (SNP) markers from a two-way
      pseudo-test cross F(1) population derived from pair-crossing of the Haifa(2) and
      LCL(2) genotypes. A total of 8 unique genomic regions on 8 linkage groups (LGs)
      of the Haifa(2) parental map and 6 unique regions on 5 LGs in the LCL(2) parental
      map were associated with plant growth under salt stress and relative growth under
      stress, as compared to control conditions. The results of this study indicate
      that salt tolerance in white clover is controlled by multiple QTLs, some at
      common locations, but each of limited magnitude. Location of these QTLs provides
      the genetic basis and potential for pyramiding of salt tolerance genes in
      breeding improvement.

PMID- 19865806
TI  - Molecular detection of genomic regions associated with grain yield and yield
      related components in an elite bread wheat cross evaluated under irrigated and
      rainfed conditions.
AB  - Grain yield and grain weight of wheat are often decreased by water-limitation in
      the north-eastern cropping belt of Australia. Based on knowledge that CIMMYT
      lines are well-adapted in this region, a recombinant inbred line (RIL) population
      between two elite CIMMYT bread wheats (Seri M82 and Babax) was evaluated under
      water-limited environments. Fourteen productivity traits were evaluated in 192
      progeny in up to eight trials. For three aggregations of the environments (all,
      high yield or low yield), multiple quantitative trait loci (QTL) were detected,
      each explaining <15% of variation. Co-location of multiple trait QTL was greatest
      on linkage groups 1B-a, 1D-b, 4A-a, 4D-a, 6A-a, 6B-a, 7A-a and an unassigned
      linkage group. Two putative QTL (LOD > 3) from Seri (6D-b and UA-d) increased
      grain yield and co-located with a suggestive (2 < LOD < 3) and a putative QTL for
      increased stem carbohydrate content (WSC), respectively; the latter QTL also co
      located with a putative anthesis QTL for earlier flowering. Both QTL were
      detected only in high yield (>4t ha(-1)) environments. A third increased grain
      yield QTL (7A-a) from Babax co-located with QTL for increased grain number. Six
      putative QTL increased grain weight and co-located with QTL for harvest index,
      grains per spike and spike number. Three putative QTL for increased grains per
      spike co-located with strong QTL for earlier flowering, increased grain weight
      and fewer spikes. A group of progeny that exceeded the mean grain yield and grain
      weight of commercial checks had an increased frequency of QTL for high WSC, large
      grain size, increased harvest index and greater height, but fewer stems, when
      compared to low yielding (20% less), low grain weight progeny. These findings
      were consistent with agronomic analyses of the germplasm and demonstrate that
      there should be opportunities to independently manipulate grain number and grain
      size which is typically difficult due to strong negative correlations.

PMID- 19865808
TI  - Medical student burnout: interdisciplinary exploration and analysis.
AB  - Burnout--a stress-related syndrome characterized by exhaustion,
      depersonalization, and a diminished sense of accomplishment--is a common
      phenomenon among medical students with significant potential consequences for
      student health, professionalism, and patient care. This essay proposes that the
      epidemic of medical student burnout can be attributed to a technocratic paradigm
      that fails to value medical students as persons with human needs and limitations.
      After briefly reviewing the literature on medical student burnout, the author
      uses two theories to elucidate potential causes: unsatisfactory aspects of the
      learning environment and a feeling one's efforts are meaningless or irrelevant.
      Cultural factors also facilitate burnout in medical students immersed in a
      clinical environment that cultivates excessive detachment from patient and self,
      impairing self-care, damaging a sense of self, and impeding the development of a
      mature, well-integrated professional identity. The ethical implications of
      medical student burnout are also addressed. Finally, this paper suggests possible
      preventive and remediative strategies such as optimizing the learning environment
      as well as narrative approaches that promise enhancement of both individual and
      institutional well-being.

PMID- 19865811
TI  - A new operative treatment for chronic biceps femoris tendon avulsion.
AB  - In this report, an original technique for augmentation of chronic biceps femoris
      tendon avulsion is described. The procedure is developed using a reverse fascia
      flap of biceps femoris to be a single-tailed graft. Then, a suture anchor is
      inserted on the fibular head to approximate and fix the retracted the biceps
      femoris. Finally, a tunnel is drilled at the proximal fibula to let the graft
      pass through, and the end of the graft loop is sutured to itself. This technique
      confers effective, firm fixation of chronic biceps femoris tendon avulsion.

PMID- 19865812
TI  - Microfracture treatment of single or multiple articular cartilage defects of the
      knee: a 5-year median follow-up of 110 patients.
AB  - We compared the results of microfracture in single versus multiple symptomatic
      articular cartilage defects in the knee in 110 patients with a median age of 38
      years (range 15-60). Cases of reoperation of the cartilage defect were classified
      as failures. Clinical outcome in non-failures was evaluated by the Lysholm score
      and grading of knee pain and function of the knee by the use of patient
      administered visual analog scales (VAS; 0-100). Data were prospectively collected
      before the operation and at the 2- to 9-year follow-up. The single lesion or the
      largest of multiple lesions were located on the medial femoral condyle (n = 62),
      trochlea (n = 18), lateral tibia (n = 11), patella (n = 10) or lateral femoral
      condyle (n = 9). We treated one (n = 76), two (n = 27) or three (n = 7) lesions
      with a median total area of 4 cm(2) (range 1-15). A total of 24 failures (22%)
      were registered-18% in the single-defect subgroup and 29% in the multiple-defects
      subgroup. In the remaining group of patients (n = 86), the mean Lysholm score,
      mean pain-score (0 = no pain; 100 = worst possible pain) and mean function-score
      (0 = useless; 100 = full function) improved from 51, 52 and 41, respectively, to
      71 (P < 0.001), 30 (P < 0.001) and 69 (P < 0.001) at the follow-up. The pain
      score was significant lower (P = 0.042), and the function-score significantly
      higher (P = 0.001) in the group of patients with a single lesion compared to the
      group with 2 or 3 lesions. The Lysholm score did not differ significantly between
      the two subgroups (P = 0.06).

PMID- 19865813
TI  - Contribution of microextraction in packed sorbent for the analysis of cotinine in
      human urine by GC-MS.
AB  - A simple, rapid, sensitive, and non-consuming solvent method for the
      determination of cotinine in urine was developed, based on sample preparation by
      the relatively new technique microextraction in packed sorbent (MEPS) and
      analysis by GC-MS. This optimized method was compared with conventional solid
      phase extraction/liquid-liquid extraction method used as reference. The wide
      linear range (5-5,000 ng/mL) and high sensitivity of the MEPS method (limit of
      detection 0.8 ng/mL) allow application to analysis of urine from smokers as well
      as non-smokers susceptible to passive smoking.

PMID- 19865814
TI  - Studies of interaction of tumor suppressor p53 with apo-MT using surface plasmon
      resonance.
AB  - The interaction of tumor suppressor p53 with apo-metallothionein (apo-MT) has
      been carried out using a flow injection-surface plasmon resonance (FI-SPR)
      instrument. MT was first tethered onto the carboxymethylated dextran film. Via
      incorporation of glycine-HCl (pH 2) to remove the sequestrated metal ions
      inherent in MT molecules, a more extended and open structure of apo-MT was
      formed. Substantial SPR angle shift corresponding to the interaction of wild-type
      p53 with apo-MT was observed. The interaction was originated from the binding
      between the free sulfhydryl groups of apo-MT and Zn(2+) of p53 with the binding
      constant of 1.4 x 10(8) M(-1). The specific binding of p53 to consensus double
      stranded DNA was hindered after metal chelation from p53 by apo-MT. Furthermore,
      inhibition of the interaction between p53 and apo-MT imposed by p53/DNA complex
      was observed. The fluorescence measurements also revealed the binding of p53 to
      apo-MT, being consistent with the SPR results. Thus, SPR could potentially serve
      as an attractive technique for monitoring p53 conformational change and
      transcriptional activity regulated by the MT/apo-MT couple.

PMID- 19865815
TI  - Optimization of a solid-phase extraction procedure in the fluorimetric
      determination of sulfonamides in milk using the second-order advantage of PARAFAC
      and D-optimal design.
AB  - The objective of this work is to optimize a solid-phase extraction procedure for
      the simultaneous determination of sulfadiazine, sulfamerazine, and sulfamethazine
      in milk by fluorimetric detection. For this task, an alternative strategy is
      employed, which allows one to reduce noticeably the number of experiments without
      losing the quality of the estimations. It consists of the use of a D-optimal
      design together with PARAFAC decomposition for the calculation of the response in
      the experimental design. Effects of amount of cartridge sorbent, kind of milk,
      volume of conditioning solutions, kind of wash and elution, and kind of mixture
      of sulfonamides have been evaluated, for maximizing sulfonamide mean recovery and
      minimizing its standard deviation. Since milk without sulfonamides may give some
      matrix effect over the fluorescence signal, its behavior has also been studied.
      Optimal conditions have been selected where the ratio between sulfonamide
      recovery and milk without sulfonamides was the highest, which are 500 mg of
      cartridge sorbent, acid wash, and elution and 3 mL of conditioning solutions. The
      type of milk and mixture of sulfonamides not significant. This makes the
      procedure suitable for the combined determination of sulfadiazine, sulfamerazine,
      and sulfamethazine in any kind of milk. Finally, an experimental procedure is
      proposed, obtaining a sulfonamide mean recovery equal to 68.5% with values of
      standard deviation between 7 and 8 microg kg(-1).

PMID- 19865816
TI  - Clinical image. High-flow priapism after perineal trauma.

PMID- 19865817
TI  - Radiographic cervical spine osteoarthritis progression rates: a longitudinal
      assessment.
AB  - Relative to other sites, the cervical spine has received little attention in the
      osteoarthritis (OA) literature. Using data from a longitudinal study, we provide
      age-specific progression rates of radiographic cervical spine OA, by gender. Data
      from cohort subjects (ages 40+) from the Clearwater Osteoarthritis Study were
      analyzed (N = 707). All study subjects' demonstrated radiographic cervical spine
      OA at baseline (2+). Lateral cervical spine radiographs were taken biennially.
      The study outcome was radiographic disease progression. A grade increase of 1, or
      more, by the Lawrence and Kellgren ordinal scale was considered progression.
      Incidence rates were calculated as per 100 person-years of observation. We show
      that the progression rates for cervical spine OA increase with age. For all ages
      combined, men demonstrated higher rates of progression compared with women.
      However, among subjects in their forties and fifties, women were more likely to
      experience worsening of their disease when compared with men. Progression rates
      were similar for men and women in their sixties (8.2 and 8.0, respectively).
      Among subjects in their seventies, men demonstrated a significantly higher rate
      of progression compared with women (12.5 and 8.6, respectively). As the baby
      boomer population continues to increase, cervical spine OA progression assessment
      can be a useful tool for health-care resource planning. Cervical spine OA
      research offers an abundance of opportunities. Instability as a precursor to the
      development of cervical spine OA warrants further research. Epidemiological
      studies addressing demographic differences (e.g., gender, age) in the incidence
      of cervical spine OA will contribute to the current knowledge base.

PMID- 19865818
TI  - Intramedullary cavernoma presenting with hematomyelia: report of two girls.
AB  - INTRODUCTION: Less than 20 children with intramedullary cavernoma (ImC) have been
      reported in the English literature; however, cases with an unfavorable outcome
      may be underreported. Whereas these are predominantly boys, we report two girls
      who presented with hematomyelia (one cervical, one thoracic) and an acute, severe
      neurological deficit. CASE MATERIAL: A 10-year-old girl complaining about lower
      thoracic pain for several days suddenly developed lower body dysesthesias and
      paraparesis. Magnetic resonance (MR) demonstrated hematomyelia (T8-T11),
      intramedullary edema (T6-L1), and an ImC at T9-T10. Within an hour, she
      progressed to paraplegia and was therefore operated immediately. She slowly
      recovered regaining independent ambulation and continence. MR after 2 years shows
      no recurrence. A 7-year-old girl suddenly developed cervicalgia and paresis of
      her left arm and leg. MR demonstrated hematomyelia and an ImC at C4-C6. She
      gradually recovered with minimal residual deficit at 3 months and was
      subsequently operated uneventfully. Multiple cerebral cavernomas and a familial
      autosomal cavernous malformation syndrome were diagnosed. The following 1.5
      years, she complained of intermittent cervicalgia and left brachial dysesthesias,
      with MR suggesting active residual cavernoma. Interestingly, her complaints
      gradually disappeared, and she is currently asymptomatic. MR after 3.5 years
      shows minimal cord swelling no longer suggesting active residual cavernoma.
      CONCLUSION: With adequate surgical treatment either in the acute phase in case of
      dramatic deterioration or after clinical recuperation, prognosis of symptomatic
      ImC may be surprisingly good. However, subtotally resected lesions and/or
      syndromal cases may recur, requiring further treatment. Definitive answers await
      more cases with longer follow-up.

PMID- 19865819
TI  - Disruption of calreticulin-mediated cellular adhesion signaling in the cadmium
      induced omphalocele in the chick model.
AB  - PURPOSE: Administration of cadmium (Cd) causes omphalocele in the chick embryo.
      The earliest histological changes in the chick Cd model are the breakdown of
      adherens junctions (AJs). Calreticulin (CRT) plays a key role in Ca(2+) signaling
      and cell adhesion. Ca(2+) signaling in the Cd chick model is known to be altered.
      The calcium-dependent adhesion molecule, E-cadherin, and its associate, beta
      catenin, are key components of AJs regulated by CRT. CRT knockouts display
      omphalocele. We hypothesized that CRT, E-cadherin and beta-catenin are
      downregulated during early embryogenesis in the Cd chick model. METHODS: After 60
      h (H) incubation, chicks were harvested 1H, 4H, and 8H post treatment with saline
      or Cd and divided into controls and Cd. RT-PCR was performed to evaluate mRNA
      levels of CRT, E-cadherin and beta-catenin in the Cd chick model. RESULTS: The
      mRNA levels of CRT were significantly decreased in the Cd group at 1H compared to
      controls (p < 0.05). The mRNA levels of E-cadherin and beta-catenin were
      significantly decreased at 4H in the Cd group compared to controls (p < 0.05).
      There were no significant differences at 8H. CONCLUSION: Downregulation of CRT, E
      cadherin and beta-catenin genes may cause omphalocele in the Cd chick model by
      disrupting CRT-mediated Ca(2+) signaling and AJs.

PMID- 19865820
TI  - Covering the colon anastomoses with amniotic membrane prevents the negative
      effects of early intraperitoneal 5-FU administration on anastomotic healing.
AB  - PURPOSE: This study investigated whether covering the colonic anastomoses with
      amniotic membrane (AM) protects the anastomotic healing from the adverse effects
      of immediate 5-fluorouracil (5-FU) administration. METHODS: One hundred twenty
      wistar albino rats were randomized to one of four groups (I-IV, 30 rats in each)
      and underwent a standardized left colon resection and anastomoses. The
      anastomoses of the rats in groups II (AM) and IV (5-FU + AM) were covered with
      AM. Saline solution (2 ml/day; groups I (control) and II) or 5-FU (20 mg/kg/day;
      groups III (5-FU) and IV) was administered to the rats intraperitoneally once
      daily from the day of operation until sacrificed. Half of each group was
      sacrificed on the postoperative day 4 (IA, IIA, IIIA, and IVA) and other half on
      the postoperative day 8 (IB, IIB, IIIB, and IVB), and their anastomoses were
      evaluated when sacrificed. RESULTS: The dehiscence rate of anastomotic dehiscence
      and adhesion formation were significantly higher in groups IIIA and IIIB compared
      with groups IVA and IVB, respectively. Bursting pressure was significantly higher
      in the 5-FU + AM groups than in the 5-FU groups. The inflammatory cell
      infiltration was significantly lower in groups IIIA and IVA compared with group
      IA, in groups IIIB and IVB compared with group IB, and in group IVA compared with
      group IIIA. Neoangiogenesis, fibroblast activity, collagen deposition, and
      hydroxyproline levels were significantly higher in the 5FU + AM groups compared
      with control and 5-FU groups. Malondialdehyde levels were significantly higher in
      the 5-FU groups than in the 5-FU + AM groups. CONCLUSION: Covering colon
      anastomoses with AM protects them, preventing leakage and reversing the negative
      effects of 5-FU administration.

PMID- 19865821
TI  - Extended lymph node dissection in colorectal cancer surgery. Reliability and
      reproducibility in assessments of operative reports.
AB  - BACKGROUND: Stratification of surgical strategies or techniques by operative
      reports is rarely validated. This study evaluates the assessment of lymph node
      dissection from operative reports and the possible survival benefit of extended
      lymph node dissection. METHODS: The operative reports of 342 colorectal
      resections (R0) were assessed twice by two surgeons. The lymph node dissection
      was classified as limited or extended according to a novel scheme. Intraobserver
      reproducibility and interobserver reliability were evaluated by kappa (kappa)
      statistics and a Cox model. RESULTS: For colonic resections, the reproducibility
      of assessments was moderate or substantial (kappa: 0.42-0.75), and the
      reliability was moderate (kappa: 0.54-0.58). For rectal resections,
      reproducibility was moderate (kappa: 0.45-0.58), and reliability was fair (kappa:
      0.29-0.36; all kappa values: p < 0.001). The 5-year survival rates of colonic
      cancer patients subject to a limited or extended procedure were 52% (45-60%, 95%
      confidence interval) and 69% (53-84%; p = 0.034), respectively. The hazard ratios
      of extended lymph node dissection (limited as reference) were 0.34 (0.14-0.86; p
      = 0.023) for stage I and II and 1.11 (0.50-2.44) for stage III. In rectal cancer
      patients, the 5-year survival rates of a limited or extended procedure were 63%
      (54-72%) and 55% (37-73), respectively. CONCLUSIONS: Valid assessment of lymph
      node dissection can be obtained from operative reports. Extended lymph node
      dissection improves long-term survival rates of colonic cancer patients.

PMID- 19865822
TI  - Bilateral vocal cord paralysis associated with laryngeal myxedema.
AB  - For managing dyspnea caused by bilateral vocal cord paralysis as a complication
      of thyroidectomy in the acute postoperative period, reversible vocal cord
      lateralisation is performed at the authors' departments. However, in the later
      postoperative period of thyroidectomy when there is no chance for recovery of the
      recurrent laryngeal nerves, they perform irreversible procedure. Applying these
      operative techniques satisfactory breathing can be achieved in about 95% of cases
      avoiding tracheostomy. In 5% of cases there are other comorbidities in the
      background of unsuccessful operative results which can cause potential dyspnea as
      well. From these complications the authors emphasize the role of laryngeal
      obstruction and myxedema as a consequence of hypothyroidism developed after
      thyroidectomy. Management of severe dyspnea caused by association of these two
      complications of thyroidectomy means a great therapeutic challenge. Between 01
      Jan 1989 and 30 Nov 2008 the authors performed 161 reversible and 135
      irreversible vocal cord lateralisations to manage dyspnea caused by bilateral
      vocal cord paralysis as a complication of thyroidectomy. From these cases four
      patients had further obstruction due to laryngeal myxedema. By performing
      endoscopic laryngeal surgeries and applying levothyroxine replacement therapy
      sufficiently wide glottic chink has been achieved in all the cases. According to
      the experience of the authors dyspnea caused by bilateral vocal cord paralysis
      after thyroidectomy needs complex, interdisciplinary therapeutic approach beside
      glottis widening operations.

PMID- 19865824
TI  - A retrospective study on the efficacy of total absorbed orbital doses of 12, 16
      and 20 Gy combined with systemic steroid treatment in patients with Graves'
      orbitopathy.
AB  - BACKGROUND: Graves' disease (GD) is an autoimmune disease that typically affects
      the thyroid gland. Thirty to sixty percent of patients also suffer from orbital
      inflammation. Retrobulbar radiotherapy for Graves' orbitopathy (GO) has been used
      for decades, though there is no direct evidence for the influence of dose and
      fractionation schedules on various signs and symptoms. Indeed, optimal
      fractionation schedules and recommended total irradiation doses are still a
      matter of discussion. Our aim was to investigate treatment efficacy of
      retrobulbar irradiation for GO at different total absorbed doses and
      fractionation schedules. METHODS: A retrospective evaluation of 129 patients who
      were examined before, as well as 6-8 months after irradiation with different
      treatment schedules at eight radiotherapeutic departments. Total absorbed doses
      were 12, 16, or 20 Gy. All patients were additionally treated with systemic
      application of corticosteroids. Treatment efficacy was evaluated through
      assessment of proptosis, horizontal and vertical ocular motility and of clinical
      activity (CAS). Overall group and individual responses were evaluated. Treatment
      response was defined as inactivation of GO, reduction of proptosis by at least 2
      mm, improvement of motility by > or = 8 degrees or unchanged normal parameters.
      RESULTS: Prior to irradiation, neither age, disease duration, gender
      distribution, smoking behavior or serologic parameters, nor clinical activity or
      severity stages varied significantly between groups. Neither did outcome
      measures, except proptosis, differ significantly. Retrobulbar irradiation led to
      inactivity of GO in approximately 80% of patients, with no significant group
      difference. After irradiation with 16 and 20 Gy, vertical motility improved in a
      significantly higher percentage of patients than after irradiation with 12 Gy.
      Median improvement of vertical motility in responding patients was excellent in
      all groups (15 degrees at 12 Gy, 10 degrees at 16 Gy, 10 degrees at 20 Gy).
      Horizontal motility did not change significantly. CONCLUSION: If the aim of
      retrobulbar irradiation is primarily to reduce soft-tissue signs, lower doses are
      sufficient. If a patient also suffers from dysmotility, doses exceeding 12 Gy may
      be more effective.

PMID- 19865823
TI  - Improved retinal function after trabeculectomy in glaucoma patients.
AB  - PURPOSE: To investigate retinal function after reduction of intraocular pressure
      (IOP) by filtration surgery in patients with medically uncontrolled glaucoma.
      METHODS: Eleven patients (11 eyes) with medically uncontrolled glaucoma underwent
      trabeculectomy. Clinical investigation, visual field (testing with standard
      automated perimetry (SAP-Humphrey), optical coherence tomography (OCT), full
      field electroretinography (full-field ERG) and multifocal electroretinography
      (mfERG) were performed preoperatively as well as 2 and 6 months after surgery.
      DESIGN: Interventional prospective, consecutive case series. RESULTS: No
      significant reduction was seen in mean log MAR visual acuity 2 or 6 months after
      filtration surgery. The mean preoperative intraocular pressure of 27.1 (+/-6.2)
      mmHg decreased to 19.0(+/-6.1) mmHg 2 months after surgery and to 17.1 (+/- 3.4)
      mmHg 6 months after surgery (both p = 0.001). The reduction in IOP significantly
      decreased the number of anti-glaucoma agents used, from 3.7 +/- 1.6 at baseline
      to 0.8 +/- 0.9 2 months after surgery and to 1.3 +/- 1.2 6 months after surgery
      (p = 0.004 and p = 0.008 respectively). The results of SAP, OCT and full-field
      ERG did not show any significant difference between pre- and postoperative values
      at any point in time. No significant improvement was found with regard to the
      first positive peak (P(1)) amplitudes in the macular retina (area 1) or in the
      perimacular retina/periphery (area 2) when measured with mfERG 2 months after
      surgery. The mfERG examinations revealed significantly improved P(1) amplitudes 6
      months after surgery in both area 1 and area 2, compared with the preoperative
      values (p = 0.042 and p = 0.014 respectively). The implicit time of P(1)
      decreased significantly 6 months after surgery in area 2 compared with the
      preoperative values (p = 0.023). CONCLUSION: A significant lowering of IOP seems
      to improve the function of the central retina, as demonstrated by increased
      amplitudes and reduced implicit times assessed with mfERG.

PMID- 19865825
TI  - Assessment of total haemoglobin mass: can it detect erythropoietin-induced blood
      manipulations?
AB  - The purpose of the study was to reveal erythropoietin (epo) doping. It was
      recently suggested that the assessment of total haemoglobin mass (tHb) by means
      of the carbon monoxide re-breathing technique should be implemented in anti
      doping work. Since epo may increase the haemoglobin concentration [Hb] simply by
      reducing plasma volume we injected eight human subjects with epo for 15 weeks and
      directly tested the feasibility hereof. Epo treatment increased [Hb] in all
      subjects at all time points (range 3.8-18.8%). In approximately half the subjects
      this was mainly the consequence of an increased tHb, but in the remaining
      subjects the change was the result of a decrease in the plasma volume. After the
      initial epo "boosting" period the assessment of tHb could not detect epo
      injections in 50% of the subjects in the remaining "maintenance" period. In our
      opinion the variability observed over time when assessing tHb is not justifiable
      in an anti-doping setting.

PMID- 19865826
TI  - Pacing accuracy in collegiate and recreational runners.
AB  - To examine runners' ability to produce a prescribed pace, we compared prescribed
      versus actual 400 m splits for collegiate (COL, n = 12) and recreational runners
      (REC, n = 16). Participants completed a VO(2max) trial and on a 400 m track,
      three 3,200 m time trials. During three subsequent sessions, participants
      completed 800 m warm-up; then, based on their fastest 3,200 m steady pace,
      subjects completed six laps total at three prescribed paces: (a) 2x 400 m at 7%
      slower than steady pace (SLO), (b) 2x 400 m at steady pace (AT) and (c) 2x 400 m
      at 7% faster than steady pace (FAS). Instructions were to complete the sets of
      two laps in prescribed times (e.g., 75 s per 400 m) (no feedback). Deviation
      scores (absolute value of difference: prescribed vs. actual time) (s) for each
      400 m lap were compared using a 2 (group) x 3 (trial) repeated measures ANOVA.
      Main effects for deviations among trials SLO (7.3 +/- 6.5), AT (6.6 +/- 6.9) and
      FAS (6.2 +/- 5.7) were not significantly different (p > 0.05). However, group
      main effect for deviation scores was significantly (p < 0.05) lower (greater
      accuracy) for COL (2.9 +/- 3.2 s) versus REC (9.5 +/- 6.6 s). Deviation scores
      were also significantly different (p < 0.05) for SLO (COL: 3.1 +/- 2.7 s, REC:
      10.4 +/- 6.7 s) and AT (COL: 1.9 +/- 1.9 s, REC: 10.1 +/- 7.2 s), with a trend
      for FAS (p = 0.06) (COL: 3.8 +/- 4.3 s, REC: 7.9 +/- 6.1 s). Bland-Altman plots
      showed better agreement (prescribed vs. actual) for COL. Experience and fitness
      of collegiate runners resulted in improved pacing accuracy.

PMID- 19865827
TI  - Non-invasive haemodynamic assessments using Innocor during standard graded
      exercise tests.
AB  - Cardiac output (Q) and stroke volume (V(S)) represent primary determinants of
      cardiovascular performance and should therefore be determined for performance
      diagnostics purposes. Since it is unknown, whether measurements of Q and V(S) can
      be performed by means of Innocor during standard graded exercise tests (GXTs),
      and whether current GXT stages are sufficiently long for the measurements to take
      place, we determined Q and V(S) at an early and late point in time on submaximal
      2 min GXT stages. 16 male cyclists (age 25.4 +/- 2.9 years, body mass 71.2 +/-
      5.0 kg) performed three GXTs and we determined Q and V(S) after 46 and 103 s at
      69, 77, and 85% peak power. We found that the rebreathings could easily be
      incorporated into the GXTs and that Q and V(S) remained unchanged between the two
      points in time on the same GXT stage (69% peak power, Q: 18.1 +/- 2.1 vs. 18.2 +/
      2.3 l min(-1), V(S): 126 +/- 18 vs. 123 +/- 21 ml; 77% peak power, Q: 20.7 +/-
      2.6 vs. 21.0 +/- 2.3 l min(-1), V(S): 132 +/- 18 vs. 131 +/- 18 ml; 85% peak
      power, Q: 21.6 +/- 2.4 vs. 21.8 +/- 2.7 l min(-1), V(S): 131 +/- 17 vs. 131 +/-
      22 ml). We conclude that Innocor may be a useful device for assessing Q and V(S)
      during GXTs, and that the adaptation of Q and V(S) to exercise-to-exercise
      transitions at moderate to high submaximal power outputs is fast enough for 1 and
      2 min GXT stage durations.

PMID- 19865828
TI  - Metabolomics investigation of exercise-modulated changes in metabolism in rat
      liver after exhaustive and endurance exercises.
AB  - Exhaustive exercise and endurance exercise training modify the physiological
      status of the body differently. The present study aimed to evaluate the
      alteration in biochemical composition with exhaustive and endurance exercises in
      rats using metabolomics strategy. The metabolite profile of liver tissue was
      investigated on gas chromatography-mass spectrometry (GC-MS). Data further
      underwent partial least-squares-discriminant analysis (PLS-DA) to compare the
      effects on metabolites in sedentary control, exhaustively exercised and endurance
      trained rats. GC-MS detected 115 highly reproducible peaks in chromatograms from
      individual liver tissue extracts, and we identified 55 of them. The three groups
      showed significant differences in metabolic profile. Changes in liver metabolism
      involved metabolites such as amino acids, fatty acids, organic acids, and
      carbohydrates. Endurance training elevated the greater rate of tricarboxylic acid
      cycle and antioxidant activity, and exhaustive exercise led to accumulated urea
      markers and an inflammation response in liver. In addition, GC-MS-based
      metabolomic analysis is a promising tool to investigate a pathological status
      with different exercise programs.

PMID- 19865830
TI  - Redescription of Balantidium polyvacuolum Li 1963 (Class: Litostomatea)
      inhabiting the intestines of Xenocyprinae fishes in Hubei, China.
AB  - Redescription of Balantidium polyvacuolum Li 1963, collected from the hindgut of
      Xenocypris davidi and Xenocypris argentea, from Niushan Lake Fishery (30 degrees
      19' N, 114 degrees 31' E) in Wuhan City, Hubei Province, China in April and June
      2007 is presented in this paper to complete Li's description at both light and
      scanning electronic microscopic levels. The unique body shape of B. polyvacuolum
      highly arched dorsal side and flattened ventral surface-as well as its remarkable
      concave platelet present in the centroventral were well described and compared
      with other close Balantidium species. Besides, two types of vestibulum shape are
      observed in our present work, which may suggest the existence of two subspecies
      or genotype species of these balantidia.

PMID- 19865829
TI  - Electrophysiological correlates of cognition improve with nap during sleep
      deprivation.
AB  - The efficacy of a 30-min nap as a countermeasure in the reduction of cognitive
      decline following 24 h of sleep deprivation (SD) on subjective sleepiness scales,
      event-related potential (ERP) P300, and contingent negative variation (CNV) was
      evaluated. The experiment was performed in three sessions on different days
      between 7 and 8 a.m. on nine normal, healthy males, of age 25-30 years: Session
      1. Baseline recordings; Session 2, after one night's total sleep deprivation,
      and; Session 3, after 1 week of Session 1, following one night's sleep
      deprivation along with a 30-min nap opportunity between 1.00 and 3.00 a.m.
      Subjective sleepiness scores increased after SD as compared to baseline, but
      reduced significantly after nap (P < 0.05). There was an increase in P3 peak
      latency of ERP following SD (16%, P < 0.01), which was reduced with nap (10.7%, P
      < 0.05).There was an increase in CNV M1 peak latency after SD (18%) which
      decreased with the use of nap (12.5%) (P < 0.01). The CNV reaction time increased
      following SD (39.3%) and decreased with the use of nap (24%) (P < 0.01). No
      significant effects on ERP N1, P1, N2 latencies, P2 and P3 amplitudes and CNV N1,
      P3, M2 peak latencies and M1, and M2 amplitudes were observed. It was concluded
      that a 30-min nap, between 1.00 and 3.00 a.m. during night SD, reduces the
      cognitive decline following 24 h of SD in terms of its electro-physiological
      correlates. The study is of applied value in optimization of cognitive
      performance in professions demanding night work schedules.

PMID- 19865831
TI  - Macroglial cells of the teleost central nervous system: a survey of the main
      types.
AB  - Following our previous review of teleost microglia, we focus here on the
      morphological and histochemical features of the three principal macroglia types
      in the teleost central nervous system (ependymal cells, astrocyte-like
      cells/radial glia and oligodendrocytes). This review is concerned with recent
      literature and not only provides insights into the various individual aspects of
      the different types of macroglial cells plus a comparison with mammalian glia,
      but also indicates the several potentials that the neural tissue of teleosts
      exhibits in neurobiological research. Indeed, some areas of the teleost brain are
      particularly suitable in terms of the establishment of a "simple" but complete
      research model (i.e. the visual pathway complex and the supramedullary neuron
      cluster in puffer fish). The relationships between neurons and glial cells are
      considered in fish, with the aim of providing an integrated picture of the
      complex ways in which neurons and glia communicate and collaborate in normal and
      injured neural tissues. The recent setting up of successful protocols for fish
      glia and mixed neuron-glia cultures, together with the molecular facilities
      offered by the knowledge of some teleost genomes, should allow consistent input
      towards the achievement of this aim.

PMID- 19865832
TI  - Effects of genotype identity and diversity on the invasiveness and invasibility
      of plant populations.
AB  - Genetic diversity within species is a potentially important, but poorly studied,
      determinant of plant community dynamics. Here we report experiments testing the
      influence of genotype identity and genotypic diversity both on the invasibility
      of a foundation, matrix-forming species (Kentucky bluegrass, Poa pratensis), and
      on the invasiveness of a colonizing species (dandelion, Taraxacum officinale).
      Genotypes of Kentucky bluegrass in monoculture showed significant variation in
      productivity and resistance to dandelion invasion, but the productivity and
      invasion resistance of genotypic mixtures were not significantly different from
      those of genotypic monocultures. Indirect evidence suggested temporal shifts in
      the genotypic composition of mixtures. Dandelion genotypes in monoculture showed
      striking and significant variation in productivity and seed production, but there
      was no significant tendency for these variables in mixtures to deviate from null
      expectations based on monocultures. However, productivity and seed production of
      dandelion mixtures were consistently greater than those of the two least
      productive genotypes, and statistically indistinguishable from those of the three
      most productive genotypes, suggesting the possibility of greater invasiveness of
      genotypically diverse populations in the long run due to dominance by highly
      productive genotypes. In both experiments, the identity of genotypes was far more
      important than genetic diversity per se.

PMID- 19865833
TI  - Evaluation of two group therapies to reduce fear of progression in cancer
      patients.
AB  - PURPOSE: This paper aims to evaluate the effects of two psychotherapeutic
      interventions on dysfunctional fear of progression (FoP) in cancer patients and
      to investigate illness-specific influences. METHODS: One hundred seventy-four
      cancer patients were recruited from two rehabilitation clinics and randomly
      assigned to either a four-session cognitive-behavioral group therapy or a
      supportive-experiential group therapy. The main outcome criterion was FoP that
      was assessed with the Fear of Progression Questionnaire (FoP-Q) directly before
      (T1) and after (T2) the intervention, as well as 3 (T3) and 12 months (T4) after
      discharge. Secondary outcomes were anxiety, depression, and quality of life that
      were assessed with the following questionnaires: Questions on Life Satisfaction,
      Questionnaire for General Health Status, and the Hospital Anxiety and Depression
      Scale. Patients from the control group (n = 91) who received treatment as usual
      were recruited 1 year later with the same inclusion criteria and assessed with
      the FoP-Q at T1, T2, and T4. RESULTS: Analyses showed a significant main effect
      for time and a significant interaction for group x time for the main outcome
      variable. FoP decreased significantly over time in both intervention groups in
      contrast to the control group that showed only short-term improvements. The
      interventions were also effective in improving secondary outcomes except general
      life satisfaction. Analyses of cancer specific influences on FoP indicated a
      significant influence of disease status, i.e., patients with metastases and
      recurrence of cancer gained most from the interventions. CONCLUSIONS: Fear of
      progression, one of the main sources of distress for cancer patients, can be
      reduced with short psychotherapeutic interventions.

PMID- 19865834
TI  - Copper redistribution in Atox1-deficient mouse fibroblast cells.
AB  - Quantitative synchrotron X-ray fluorescence (SXRF) imaging of adherent mouse
      fibroblast cells deficient in antioxidant-1 (Atox1), a metallochaperone protein
      responsible for delivering Cu to cuproenzymes in the trans-Golgi network,
      revealed striking differences in the subcellular Cu distribution compared with
      wild-type cells. Whereas the latter showed a pronounced perinuclear localization
      of Cu, the Atox1-deficient cells displayed a mostly unstructured and diffuse
      distribution throughout the entire cell body. Comparison of the SXRF elemental
      maps for Zn and Fe of the same samples showed no marked differences between the
      two cell lines. The data underscore the importance of Atox1, not only as a
      metallochaperone for delivering Cu to cuproenzymes, but also as a key player in
      maintaining the proper distribution and organization of Cu at the cellular level.

PMID- 19865835
TI  - Selectivity of Imidacloprid for fruit fly versus rat nicotinic acetylcholine
      receptors by molecular modeling.
AB  - For better understanding of the mechanisms of selective binding of the
      representative nicotinic acetylcholine receptor (nAChR) agonist neonicotinoid
      Imidacloprid (IMI), three-dimensional models of fruit fly alpha 1 beta 2 and rat
      alpha 4beta 2 nAChRs were generated by homology modeling, using the crystal
      structure of the acetylcholine-binding protein (AChBP) of Lymnaea stagnalis and
      the nAChR of mus musculus as the templates, respectively. The conformational
      stability of the two models was studied by molecular dynamics (MD) and the
      quality of the models was confirmed. Especially, insecticide Imidacloprid was
      docked into the putative binding site of the fruit fly alpha 1 beta 2 and rat
      alpha 4 beta 2 nAChRs by Surflex-docking. The calculated docking energies were in
      agreement with the experimental data and the putative binding sites were also
      consistent with the results from labeling and mutagenesis experiments.
      Furthermore, the mechanisms of Imidacloprid selectively acting on fruit fly
      versus rat nAChRs were discussed.

PMID- 19865836
TI  - Application of bone growth factors--the potential of different carrier systems.
AB  - AIM: The aim of the present review was to characterize the potential of different
      biomaterials as carriers for bone growth factors. INTRODUCTION: Beyond mechanical
      and structural characteristics, one of the features that account for a potential
      carrier is the possibility to couple growth factor molecules to it. As simple
      adsorption of the growth factor to the carrier surface by soak loading produces a
      burst release of growth factors with rapid decrease of biological activity, the
      ability to accomplish controlled release of functional growth factor molecules is
      one of the crucial characteristics for an appropriate carrier material.
      CONCLUSION: The variety of carrier materials requires different strategies to
      either couple growth factors to the material surface or to incorporate them into
      the carrier matrix. The present review outlines current technical approaches and
      discusses future trends in the use of carrier materials for bone growth factors.

PMID- 19865837
TI  - Implant migration into maxillary sinus: description of two asymptomatic cases.
AB  - BACKGROUND: Rehabilitation of edentulous jaws with dental implants has become a
      usual practice around the world. A very low incidence of complications is
      associated with this therapy. One of them is migration of dental implants into
      maxillary sinus. Foreign bodies inside maxillary sinus should be removed because
      they can cause sinusitis, but if any symptoms are present, preservation alone can
      be indicated. Implant removal and bone reconstruction on the same procedure
      reduce treatment time and allow rehabilitation with implant-supported prosthesis.
      METHODS: In the present study, we report two cases of dental implants displaced
      into maxillary sinus that receive different treatment. RESULTS: In one of them,
      implant removal and sinus lift were carried out on same procedure while on the
      other preservation alone was advocated. CONCLUSION: Both treatment modalities
      treatments allowed installation of implant-supported prosthesis.

PMID- 19865840
TI  - Influence of power-law rheology on cell injury during microbubble flows.
AB  - The reopening of fluid-occluded pulmonary airways generates microbubble flows
      which impart complex hydrodynamic stresses to the epithelial cells lining airway
      walls. In this study we used boundary element solutions and finite element
      techniques to investigate how cell rheology influences the deformation and injury
      of cells during microbubble flows. An optimized Prony-Dirichlet series was used
      to model the cells' power-law rheology (PLR) and results were compared with a
      Maxwell fluid model. Results indicate that membrane strain and the risk for cell
      injury decreases with increasing channel height and bubble speed. In addition,
      the Maxwell and PLR models both indicate that increased viscous damping results
      in less cellular deformation/injury. However, only the PLR model was consistent
      with the experimental observation that cell injury is not a function of stress
      exposure duration. Correlation of our models with experimental observations
      therefore highlights the importance of using PLR in computational models of cell
      mechanics/deformation. These computational models also indicate that altering the
      cell's viscoelastic properties may be a clinically relevant way to mitigate
      microbubble-induced cell injury.

PMID- 19865839
TI  - Streptococcal protective antigens (Spa): a new family of type-specific proteins
      of group A streptococci.
AB  - Previous studies in our laboratory described a new group A streptococcal
      protective antigen (Spa) in type 18 streptococci that was distinct from the type
      18 M protein. This study was undertaken to identify additional serotypes of group
      A streptococci that express Spa proteins. PCR techniques were used to identify
      and clone a new spa gene from type 36 streptococci. The 5' sequence of spa36 was
      highly variable compared to spa18, while the 3' sequence was conserved. Antisera
      against Spa36 opsonized type 36 streptococci but not type 18 streptococci,
      indicating that the opsonic Spa epitopes were type-specific. Antisera against the
      conserved carboxy-terminal half of Spa18 were used to identify Spa or Spa-like
      proteins expressed on the surface of 25 of 70 different serotypes of GAS. Spa
      proteins may represent a new family of type-specific surface antigens that
      function in concert with M proteins to elicit protective immune responses.

PMID- 19865841
TI  - Nocturia and snoring: predictive symptoms for obstructive sleep apnea.
AB  - PURPOSE: Current screening for obstructive sleep apnea (OSA) emphasizes self
      reported snoring and other breathing symptoms. Nocturia, a symptom with a precise
      pathophysiological link to sleep apnea, has not been assessed as a screening tool
      for this common disorder of sleep respiration. In a large sample of adults
      presenting to area sleep centers, we aimed to determine the predictive power of
      nocturia for OSA and compare findings with other markers of OSA commonly used to
      screen for this disease. METHODS: This was a retrospective chart review. A
      consecutive sample of 1,007 adult patients seeking treatment at two sleep centers
      in New Mexico completed detailed medical and sleep history questionnaires and
      completed diagnostic polysomnography testing. The sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of nocturia,
      snoring, high body mass index, sex, and age for OSA were determined. Hierarchical
      linear regression determined unique variance contribution to the apnea-hypopnea
      index, the objective measure of sleep apnea severity. RESULTS: The results are as
      follows: sensitivities--snoring, 82.6% and nocturia, 84.8%; specificities-
      snoring, 43.0% and nocturia, 22.4%; PPVs--snoring, 84.7% and nocturia, 80.6%; and
      NPVs--snoring, 39.6% and nocturia, 27.9%. With hierarchical linear regression,
      patient-reported nocturia frequency predicted apnea-hypopnea index (OSA severity)
      above and beyond body mass index, sex, age, and self-reported snoring (P<0.0001).
      CONCLUSIONS: Nocturia appears comparable to snoring as a screening tool for OSA
      in patients presenting to a sleep medical center. Research in urology and primary
      care clinics is needed to definitively clarify the use of nocturia as a screening
      instrument for obstructive sleep apnea.

PMID- 19865842
TI  - Development of a framework for reporting health service models for managing
      rheumatoid arthritis.
AB  - The purpose of this study was to develop a framework for reporting health service
      models for managing rheumatoid arthritis (RA). We conducted a search of the
      health sciences literature for primary studies that described interventions which
      aimed to improve the implementation of health services in adults with RA.
      Thereafter, a nominal group consensus process was used to synthesize the evidence
      for the development of the reporting framework. Of the 2,033 citations screened,
      68 primary studies were included which described 93 health service models for RA.
      The origin and meaning of the labels given to these health service delivery
      models varied widely and, in general, the reporting of their components lacked
      detail or was absent. The six dimensions underlying the framework for reporting
      RA health service delivery models are: (1) Why was it founded? (2) Who was
      involved? (3) What were the roles of those participating? (4) When were the
      services provided? (5) Where were the services provided/received? (6) How were
      the services/interventions accessed and implemented, how long was the
      intervention, how did individuals involved communicate, and how was the model
      supported/sustained? The proposed framework has the potential to facilitate
      knowledge exchange among clinicians, researchers, and decision makers in the area
      of health service delivery. Future work includes the validation of the framework
      with national and international stakeholders such as clinicians, health care
      administrators, and health services researchers.

PMID- 19866231
TI  - Ileocecal herniation through the foramen of Winslow: MDCT diagnosis.
AB  - We report a rare case of small bowel obstruction of a 45-year-old female which
      was caused by internal hernia of the terminal ileum and cecum through the foramen
      of Winslow. The patient presented to the emergency department with acute
      abdominal pain, distention, and nausea, suggesting an intestinal obstruction. The
      complete unambiguous preoperative diagnosis was achieved by a 64-row multi
      detector computed tomography. This report enlightens the utility and performances
      of high-quality computed tomography multiplanar reconstructions combined with
      vascular volume rendering analysis for the diagnosis of internal hernia.

PMID- 19866232
TI  - Traumatic splenic injury managed with arterial embolisation in a patient with
      idiopathic thrombocytopenic pupura.

PMID- 19866233
TI  - Emergency endovascular treatment of sac rupture for type IIIa endoleak in
      thoracic aortic aneurysm previously excluded with endovascular repair.
AB  - Elective endovascular treatment of thoracic aortic pathology has been applied in
      a variety of conditions. The complications of thoracic aortic stenting are also
      well recognized. Endoleak after endovascular repair of thoracic aortic aneurysms
      is the most frequent complication; among them, type III is the least frequent.
      Endovascular treatment of type III endoleak is generally performed under elective
      conditions; less frequently, in emergency. We report a successful emergency
      endovascular management of post-thoracic endovascular repair for thoracic aortic
      aneurysm rupture due to type IIIa endoleak.

PMID- 19866234
TI  - Upper gastrointestinal investigations before gastric banding.
AB  - BACKGROUND: Long-term complications after laparoscopic gastric banding (LAGB) are
      frequent, leading to reoperations for a substantial number of patients. It is not
      known whether esophageal motility or the lower esophageal sphincter (LES) play a
      role in the development of complications. The results of preoperative upper
      gastrointestinal (GI) testing were compared with outcome after LAGB. METHODS:
      Before LAGB, 68 bariatric patients had esophageal manometry, endoscopy, and pH
      monitoring. For 61 of these patients (90% follow-up rate), the differences in
      weight loss, complications, and reoperation rate were retrospectively compared.
      RESULTS: Of these patients, 8.2% had a nonspecific motility disorder of the
      esophagus, 44.3% had an incompetent sphincter shown by manometry, and 17.5% had
      acid reflux shown by pH monitoring. Endoscopic evaluation showed esophagitis in
      10.3% and hiatal hernia in 33.8% of the patients. Abnormal pH monitoring and
      endoscopic findings were not predictive for the long-term outcome or
      complications. The presence of an incompetent LES led to reoperation for a
      greater number of patients (44.4 vs. 14.7%; p = 0.01), especially if the band was
      placed using the pars flaccida technique. CONCLUSIONS: Endoscopy and pH
      monitoring do not predict outcome for gastric banding and therefore have no
      relevance in the selection of patients for gastric banding. Patients with an
      incompetent LES shown by manometry had a higher reoperation rate. If this finding
      can be confirmed, patients with LES incompetence may need another intervention.

PMID- 19866235
TI  - Long-term effects of laparoscopic sleeve gastrectomy, gastric bypass, and
      adjustable gastric banding on type 2 diabetes.
AB  - BACKGROUND: This study aimed to compare the efficacy of laparoscopic sleeve
      gastrectomy (SG) with that of laparoscopic gastric bypass (GBP) and laparoscopic
      adjustable gastric banding (AGB) for glucose homeostasis in morbidly obese
      subjects with type 2 diabetes mellitus (T2DM) at a 3-year follow-up assessment
      and to elucidate the role of weight loss in the T2DM resolution after SG.
      METHODS: For this study, 60 morbidly obese T2DM patients (44 females and 16
      males) who underwent AGB (24 patients), GBP (16 patients), or SG (20 patients)
      between 1996 and 2008 were retrospectively analyzed. Age, sex, body mass index
      (BMI), estimated weight loss (EWL), fasting glycemia, HbA1c, euglycemic
      hyperinsulinemic clamp, discontinuation of diabetes treatment, and time until
      interruption of therapy were evaluated. RESULTS: In the study, 54 patients
      received oral hypoglycemic agents for at least 12 months before surgery, and 6
      patients received insulin. The mean follow-up period was 36 months. The
      resolution rate was 60.8% for the AGB patients, 81.2% for the GBP patients, and
      80.9% for the SG patients. The postoperative time until interruption of therapy
      was 12.6 months for the AGB patients, 3.2 months for the GBP patients, and 3.3
      months for the SG patients. The hyperinsulinemic euglycemic clamp test was
      performed 12 months after surgery for the cured patients. Insulin resistance was
      restored to normal values in all the patients. The greatest improvement from
      preoperative values occurred in the SG group. For the not-cured GBP and SG
      patients, an improvement of 120 mg/dl in fasting plasma glucose was observed 3
      months after the surgery, suggesting an enhancement in insulin sensitivity, which
      determines better medical control. The resolution rate remained constant at the
      36-month follow-up evaluation in both the GBP and SG groups. CONCLUSIONS: All
      three bariatric procedures are effective in treating diabetes, with a 3-year
      follow-up evaluation showing an effect that lasts. The AGB procedure was the
      least effective. The antidiabetic effect was similarly precocious after GBP and
      SG compared with AGB. This difference may indicate that a hormonal mechanism may
      be involved, independent of weight loss.

PMID- 19866236
TI  - Ergonomics of disposable handles for minimally invasive surgery.
AB  - BACKGROUND: The ergonomic deficiencies of currently available minimally invasive
      surgery (MIS) instrument handles have been addressed in many studies. In this
      study, a new ergonomic pistol handle concept, realized as a prototype, and two
      disposable ring handles were investigated according to ergonomic properties set
      by new European standards. METHODS: In this study, 25 volunteers performed four
      practical tasks to evaluate the ergonomics of the handles used in standard
      operating procedures (e.g., measuring a suture and cutting to length, precise
      maneuvering and targeting, and dissection of a gallbladder). Moreover, 20
      participants underwent electromyography (EMG) tests to measure the muscle strain
      they experienced while carrying out the basic functions (grasp, rotate, and
      maneuver) in the x, y, and z axes. The data measured included the number of
      errors, the time required for task completion, perception of pressure areas, and
      EMG data. The values for usability in the test were effectiveness, efficiency,
      and user satisfaction. Surveys relating to the subjective rating were completed
      after each task for each of the three handles tested. RESULTS: Each handle except
      the new prototype caused pressure areas and pain. Extreme differences in muscle
      strain could not be observed for any of the three handles. Experienced surgeons
      worked more quickly with the prototype when measuring and cutting a suture
      (approximately 20%) and during precise maneuvering and targeting (approximately
      20%). On the other hand, they completed the dissection task faster with the
      handle manufactured by Ethicon. Fewer errors were made with the prototype in
      dissection of the gallbladder. In contrast to the handles available on the
      market, the prototype was always rated as positive by the volunteers in the
      subjective surveys. CONCLUSIONS: None of the handles could fulfil all of the
      requirements with top scores. Each handle had its advantages and disadvantages.
      In contrast to the ring handles, the volunteers could fulfil most of the tasks
      more efficiently using the prototype handle without any remarkable pressure
      areas, cramps, or pain.

PMID- 19866237
TI  - A review of ant cuticular hydrocarbons.
AB  - We compared the published cuticular hydrocarbon (CHC) profiles of 78 ant species
      across 5 subfamilies. Almost 1,000 CHCs have been described for these species,
      composing 187 distinct homologous series and ten hydrocarbon groups. In
      descending order of occurrence were: n-alkanes > monomethylalkanes >
      dimethylalkanes > alkenes > dienes>> trimethylalkanes>> methylalkenes >
      methylalkadienes > trienes > tetramethylalkanes. Odd chain lengths and positions
      of methyl or double bonds at odd carbon numbers were far more numerous than even
      chain-length compounds or bond positions. Although each species possess its own
      unique pattern of CHCs, we found no association between CHC profile and
      phylogeny. The production of the biosynthetically complex compounds (e.g., methyl
      branched dienes) by the most primitive living ant suggests that the basic genetic
      architecture required to produce the rich diversity of CHCs was already present
      prior to their adaptive radiation. Unlike the ubiquitous n-alkanes and
      monomethylalkanes, there is a huge diversity of species-specific dimethylalkanes
      that makes them likely candidates for species and nest-mate discrimination
      signals.

PMID- 19866238
TI  - Sentinel lymph node dissection in primary melanoma reduces subsequent regional
      lymph node metastasis as well as distant metastasis after nodal involvement.
AB  - BACKGROUND: In many countries sentinel lymph node dissection (SLND) followed by
      complete lymphadenectomy if positive is routinely performed treatment for primary
      cutaneous melanoma. However, the potential survival benefit of SLND is still
      controversial. METHODS: Patients with primary cutaneous melanoma (tumor thickness
      1.00 mm or greater) diagnosed in the Department of Dermatology, University of
      Tuebingen, Germany between 1991 and 2000 were included in the study. A total of
      439 patients who received SLND were compared retrospectively with 440 patients
      without SLND with regards to occurring patterns of metastases and disease-free
      and overall survival. SLND-positive cases and SLND-negative patients with
      subsequent development of regional lymph node metastasis (SLND-LN+) were compared
      with non-SLND patients who had developed regional lymph node metastasis (non-SLND
      LN+). RESULTS: Regional lymph node metastases as the first recurrence occurred
      more frequently in the non-SLND collective (16.5%) compared with the SLND group
      (7.3%; P = 0.001), whereas satellite/in-transit metastases and distant metastases
      did not differ. Driven by the reduction of regional lymph node metastases,
      disease-free survival was improved in the SLND collective (P = 0.003). No
      significant difference in overall survival was observed (P = 0.090).The risk of
      dying from melanoma was 2.2 times higher in the non-SLND-LN+ group than in the
      SLND-LN+ group (P = 0.009), while the risk of developing distant metastasis was
      2.3 times higher (P = 0.002). CONCLUSIONS: SLND reduced subsequent regional lymph
      node metastases and improved disease-free survival, while overall survival
      remained unaffected. SLND reduced distant metastases and improved overall
      survival in the subgroups of patients with regional lymph node involvement.

PMID- 19866239
TI  - CKS1B overexpression implicates clinical aggressiveness of hepatocellular
      carcinomas but not p27(Kip1) protein turnover: an independent prognosticator with
      potential p27 (Kip1)-independent oncogenic attributes?
AB  - BACKGROUND: Through data mining the Stanford Microarray Database, the CKS1B
      transcript was found to be frequently upregulated in hepatocellular carcinomas
      (HCCs) with low alpha-fetal protein (AFP) expression. Together with SKP2, CKS1B
      is known to implicate p27(Kip1) protein turnover promoting cell-cycle
      progression. METHODS: CKS1B, p27(Kip1), and SKP2 were immunostained in 75 HCCs
      and correlated with clinicopathological features, local recurrence-free survival
      (LRFS), and overall survival (OS). Silencing of CKS1B and SKP2 with interference
      short-hairpin RNA (shRNA) was performed in SK-Hep1 and Hep-3B cell lines.
      RESULTS: Immunohistochemically, increased CKS1B and SKP2, and attenuated
      p27(Kip1) were all associated with tumor multiplicity (P < 0.05) and increasing
      American Joint Committee on Cancer (AJCC) stage (P < 0.05). Overexpression of
      CKS1B significantly correlated with advanced Okuda stages (P = 0.048) and SKP2
      overexpression (P = 0.047). Neither CKS1B nor SKP2 was inversely related to
      p27(Kip1), which was reinforced by no alteration in p27(Kip1) abundance in HCC
      derived cells with CKS1B or SKP2 silencing. Both CKS1B overexpression (P = 0.0011
      and P = 0.0017) and p27(Kip1) attenuation (P = 0.0079 and P = 0.0085) were
      predictive of OS and LRFS, respectively, while SKP2 overexpression was associated
      with worse OS alone (P = 0.0043). Combined assessment of CKS1B and p27(Kip1) was
      able to robustly distinguish three prognostically different groups (P < 0.0001).
      In multivariate comparison, CKS1B overexpression represented the strongest
      independent adverse prognosticator [OS, P = 0.0235, hazard ratio (HR): 4.193;
      LRFS, P = 0.0204, HR: 4.262], followed by p27(Kip1) attenuation (OS, P = 0.0320,
      HR: 2.553; LRFS, P = 0.0262, HR: 2.533). CONCLUSIONS: CKS1B protein
      overexpression in HCCs is implicated in clinical aggressiveness but not in
      p27(Kip1) turnover, implying presence of p27(Kip1)-independent oncogenic
      attributes. The combined assessment of CKS1B and p27(Kip1) immunoexpressions
      effectively risk-stratifies HCCs with different prognoses, which may aid in the
      management of this deadly malignancy.

PMID- 19866240
TI  - Malignant ascites symptom cluster in patients referred for paracentesis.
AB  - BACKGROUND: Malignant ascites (MA) is a distressing problem usually managed by
      repeated paracenteses. Paracentesis represents a meaningful time point in
      identifying patients with a specific presentation. OBJECTIVE: The objective of
      this study is to examine symptom clustering in MA patients at paracentesis.
      METHODS: Pre- and post-paracentesis, patients completed the Edmonton Symptom
      Assessment Scale revised to include abdominal distension and mobility (ESAS:AM)
      and the European Organization for Research and Treatment of Cancer Quality of
      Life Questionnaire (EORTC QLQ-C30). This is a secondary analysis of data
      previously published, which reported on the validity of these surveys in MA. The
      symptoms were clustered using a hierarchical cluster analysis technique. RESULTS:
      In 37 cancer patients with complete data, there were two clusters common at both
      pre- and post-paracentesis time points: (1) depression-anxiety; (2) fatigue
      appetite-wellbeing-mobility. Paracentesis resulted in an improvement in ESAS/AM
      total score (SDS/AM), abdominal distension, and shortness of breath (P < 0.001,
      threshold adjusted for multiple comparisons). On the EORTC QLQ-C30, the domains
      of role functioning and global quality of life (QOL) showed a trend towards
      improvement, while the domains of cognitive and emotional QOL declined
      significantly (P < 0.001, threshold adjusted for multiple comparisons), despite
      improvement in individual symptoms commonly attributed to ascites. CONCLUSIONS:
      This study is the first to describe symptom clusters in MA. Studies in MA should
      include measurement of the more global symptoms of fatigue, wellbeing,
      depression, and anxiety in addition to shortness of breath, abdominal distension,
      and mobility. Patients presenting with MA require a comprehensive assessment and
      a management plan that addresses QOL and the emotional domain symptoms shown to
      cluster in these patients.

PMID- 19866241
TI  - Acute compartment syndrome of the forearm following autologous blood reinfusion:
      a case report.
AB  - Compartment syndrome is a condition with multiple reported etiologies, and
      permanent disability may ensue if not treated in a timely fashion. We report the
      first case, to our knowledge, of acute forearm compartment syndrome caused by
      intravenous autologous blood reinfusion. The patient underwent forearm
      fasciotomy, and hematoma was encountered deep to the superficial volar fascia,
      presumably extravasated from the reinfusion catheter. With the rise in the number
      of knee and hip arthroplasties, surgeons need a heightened awareness of the
      possible complications and morbidity associated with a presumed increase in
      autologous blood reinfusion.

PMID- 19866243
TI  - Interaction analysis and psychology: a dialogical perspective.
AB  - Interaction analysis is not a prerogative of any discipline in social sciences.
      It has its own history within each disciplinary field and is related to specific
      research objects. From the standpoint of psychology, this article first draws
      upon a distinction between factorial and dialogical conceptions of interaction.
      It then briefly presents the basis of a dialogical approach in psychology and
      focuses upon four basic assumptions. Each of them is examined on a theoretical
      and on a methodological level with a leading question: to what extent is it
      possible to develop analytical tools that are fully coherent with dialogical
      assumptions? The conclusion stresses the difficulty of developing methodological
      tools that are fully consistent with dialogical assumptions and argues that there
      is an unavoidable tension between accounting for the complexity of an interaction
      and using methodological tools which necessarily "monologise" this complexity.

PMID- 19866242
TI  - Adipocyte accumulation of long-chain fatty acids in obesity is multifactorial,
      resulting from increased fatty acid uptake and decreased activity of genes
      involved in fat utilization.
AB  - BACKGROUND: The obesity epidemic causes significant morbidity and mortality.
      Knowledge of cellular function and gene expression in obese adipose tissue will
      yield insights into obesity pathogenesis and suggest therapeutic targets. The aim
      of this work is to study the processes determining fat accumulation in adipose
      tissue from obese patients. METHODS: Omental fat was collected from two cohorts
      of obese bariatric surgery patients and sex-matched normal-weight donors.
      Isolated adipocytes were compared for cell size, volume, and long-chain fatty
      acid (LCFA) uptake. Omental fat RNAs were screened by 10K microarray (cohort 1:
      three obese, three normal) or Whole Genome microarray (cohort 2: seven obese,
      four normal). Statistical differences in gene and pathway expression were
      identified in cohort 1 using the GeneSifter Software (Geospiza) with key results
      confirmed in cohort 2 samples by microarray, quantitative real-time polymerase
      chain reaction, and pathway analysis. RESULTS: Obese omental adipocytes had
      increased surface area, volume, and V (max) for saturable LCFA uptake. Dodecenoyl
      coenzyme A delta isomerase, central to LCFA metabolism, was approximately 1.6
      fold underexpressed in obese fat in cohorts 1 and 2. Additionally, the Kyoto
      Encyclopedia of Genes and Genomics pathway analysis identified oxidative
      phosphorylation and fatty acid metabolism pathways as having coordinate,
      nonrandom downregulation of gene expression in both cohorts. CONCLUSIONS: In
      obese omental fat, saturable adipocyte LCFA uptake was greater than in controls,
      and expression of key genes involved in lipolysis, beta-oxidation, and metabolism
      of fatty acids was reduced. Thus, both increased uptake and reduced metabolism of
      LCFAs contribute to the accumulation of LCFAs in obese adipocytes.

PMID- 19866244
TI  - Tracheal intubation with the AirwayScope videolaryngoscope using straight vs
      curved reinforced tubes.

PMID- 19866332
TI  - Regular surveillance by imaging for early detection and better prognosis of
      hepatocellular carcinoma in patients infected with hepatitis C virus.
AB  - PURPOSE: This study evaluated the usefulness of regular check-ups by
      ultrasonography and contrast-enhanced imaging for early detection of
      hepatocellular carcinoma (HCC) in a retrospective analysis. PATIENTS AND METHODS:
      From April 2001 to March 2007, 240 consecutive patients with HCC who were
      infected with hepatitis C virus (HCV) were divided into three groups. Patients
      diagnosed with HCC by repeated imaging constituted Group A (surveillance group).
      Group B comprised patients in whom HCC was detected during scheduled doctor
      visits for liver disease or other diseases such as diabetes. Group C comprised
      non-screened patients. RESULTS: The prevalence of solitary tumors decreased from
      Group A through Group B to Group C (66, 48 and 24%, respectively, P < 0.001). The
      proportion of patients in stages I and II decreased from 83% (103/124) in Group A
      to 53% (42/79) in Group B and 24% (9/37) in Group C (P < 0.001). The proportion
      of patients who were treated with curative procedures, such as resection or
      ablation, was highest at 80% (99/124) in Group A, and lower at 53% (42/79) in
      Group B and 27% (10/37) in Group C (P < 0.001). The cumulative survival rate was
      better in Group A than B (P < 0.05), and in Group B than C (P < 0.001).
      Periodical medical check-ups without imaging did not necessarily detect early
      stage disease, even when HCC-related markers including des-gamma-carboxy
      prothrombin were tested. CONCLUSIONS: Regular surveillance with ultrasonography
      and contrast-enhanced imaging is useful for detecting early-stage HCC and
      increase chances for curative treatments in patients with HCV-related chronic
      liver disease.

PMID- 19866335
TI  - FDG PET findings in a case with acute pulmonary silicosis.
AB  - A 21-year-old male having a history of 4 years of working at a denim factory as a
      sandblaster was diagnosed with pulmonary silicosis and he was also an active
      smoker. Productive cough, dyspnea on effort, night sweats, and weight loss in a
      short period of time were his complaints. Chronic occupational exposure to tiny
      particles of silicon dioxide can stimulate parenchymal inflammation, collagen
      synthesis and, ultimately pulmonary fibrosis called silicosis. A typical history
      of exposure and chest X-ray is usually enough for diagnosis. No effective
      treatment exists except supportive care. Although chest X-ray of the patient
      revealed bilateral disseminated micronodular densities, a peripherally diffuse
      prominent FDG [(F-18)-2-fluoro-2-deoxy-D-glucose] uptake in both lungs and faint
      FDG uptake in mediastinal lymph nodes demonstrating active inflammation regions
      were noted on PET (Positron Emission Tomography) scan. This case was presented to
      show the active disease discriminated by FDG PET from chronic changes detected by
      radiological studies. FDG PET can provide additional information to CT regarding
      the diagnosis of acute silicosis and the rare accelerated silicosis.

PMID- 19866334
TI  - Antitumor necrotic factor agent promotes BMP-2-induced ectopic bone formation.
AB  - Etanercept (ETN), which is a recombinant human soluble tumor necrosis factor
      (TNF) receptor that inhibits TNF activity, is effective in the treatment of
      rheumatoid arthritis. We investigated the effect of ETN on recombinant human bone
      morphogenetic protein-2 (rhBMP-2)-induced ectopic bone formation in vivo. A block
      copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone
      and polyethylene glycol (PLA-DX-PEG polymer) was used as the delivery system.
      Polymer discs (6 mm, 30 mg) containing 5 microg rhBMP-2 were implanted into the
      left dorsal muscle pouch of mice (n = 50). In the systemic administration groups
      (n = 5 per group), ETN was subcutaneously injected (25 mg/human = 12.5
      microg/mouse) twice per week in a dose-dependent manner (placebo, 12.5 x 10(-3),
      12.5 x 10(-1), 12.5, 125 microg), whereas a single dose of ETN (placebo, 12.5 x
      10(-3), 12.5 x 10(-1), 12.5, 125 microg) was embedded in each rhBMP-2 polymer
      disc in the local administration groups (n = 5 per group). Three weeks after
      implantation, the mice were killed and the implants were analyzed. Implants in
      the optimally dosed groups had increased radiodensity, which was consistent with
      a significant increase in bone mineral content of the ossicles. Bone
      histomorphology revealed a significant increase in bone volume/total volume,
      number of osteoblasts, osteoblast surface/bone surface, and a significant
      decrease in the number of osteoclasts, osteoclast surface/bone surface in the
      optimal dosed systemic and locally administered groups. These data suggest that
      the optimal dose of ETN, administered either systemically or locally, enhanced
      the bone-inducing capacity of BMP with no apparent adverse systemic effects.

PMID- 19866336
TI  - Living-donor single lobe lung transplantation for bronchiolitis obliterans from
      mother to child following previous allogeneic hematopoietic stem cell
      transplantation from the same donor.

PMID- 19866337
TI  - Treosulfan-based conditioning regimen in a second matched unrelated peripheral
      blood stem cell transplantation for a pediatric patient with CGD and invasive
      aspergillosis, who experienced initial graft failure after RIC.
AB  - Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by
      a defect of phagocyte NADPH-oxidase and characterized by severe, recurrent
      bacterial and fungal infections. Invasive aspergillosis (IA) is the leading cause
      of mortality in patients with CGD. We report the case of a 3-year-old boy with
      CGD, who developed IA despite antifungal prophylaxis. His treatment consisted of
      a 10-month-long multi-drug antifungal therapy, together with surgery, but these
      did not cause any substantial clinical improvement. BMT in high-risk patients
      with CGD remains a challenge due to both, higher risk of graft rejection and
      inflammatory flare in the course of immune recovery. Our patient rejected the
      first matched unrelated donor (MUD) allograft after RIC regimen recommended by
      the EBMT Inborn Errors Working Party for high-risk patients. After treosulfan
      based conditioning and second MUD peripheral blood stem cell transplantation
      both, full reconstitution of the granulocytic series and complete recovery from
      IA, were achieved.

PMID- 19866338
TI  - Lipopolysaccharide-induced radical formation in the striatum is abolished in Nox2
      gp91phox-deficient mice.
AB  - Encephalopathy associated with septic shock as well as psychiatric disorders can
      be caused by the central nervous formation of reactive oxygen species (ROS)
      associated with inflammation. The systemic application of lipopolysaccharide
      (LPS, 100 mug/kg i.p.) also serves as a model for major depression and results in
      enhanced inflammatory processes. which are characterized by the stimulation of
      microglia or macrophages that then impair normal brain function. The aim of the
      present study was to analyze the effect of peripherally applied LPS on the
      central nervous formation of ROS and IL-6 in wild-type mice and in mice lacking
      the NADPH oxidase Nox2 subunit gp91phox. Microdialysis was performed in the
      striatum of the mice. Central nervous ROS were detected by electron spin
      resonance spectroscopy using 1-hydroxy-3-methoxycarbonyl-2,2,5,5
      tetramethylpyrrolidine (CMH) as reactant, which was infused via a microdialysis
      probe. IL-6 was measured in microdialysis samples by an immunoassay. Finally,
      blood samples were taken by heart puncture to detect IL-6 in plasma. In the wild
      type mice, LPS significantly increased the ROS formation in the striatum of wild
      type mice and resulted in a significantly enhanced IL-6 production. In the mice
      lacking the NADPH oxidase Nox2 subunit gp91phox, LPS did not enhance ROS
      formation, while central IL-6 was significantly increased. IL-6 plasma values
      were enhanced in both types of mice. In conclusion, the gp91phox-containing NADPH
      oxidase complex is involved in the central nervous ROS formation after peripheral
      LPS stimulation and might be a pharmacological target in patients with septic
      shock.

PMID- 19866339
TI  - Antioxidant strategy to rescue synaptosomes from oxidative damage and energy
      failure in neurotoxic models in rats: protective role of S-allylcysteine.
AB  - The functional preservation of nerve endings since the early stages of toxicity
      in a given damaging insult-either acute or chronic-by means of antioxidant and
      neuroprotective agents is a primary need to design therapeutic strategies for
      neurodegenerative disorders, with particular emphasis on those diseases with
      excitotoxic and depleted energy metabolism components. S-allylcysteine (SAC), a
      well-known antioxidant agent, was tested as a post-treatment in different in
      vitro and in vivo neurotoxic models. Quinolinic acid (QUIN) was used as a typical
      excitotoxic/pro-oxidant inducer, 3-nitropropionic acid (3-NP) was employed as a
      mitochondrial function inhibitor, and their combination (QUIN + 3-NP) was also
      evaluated in in vitro studies. For in vitro purposes, increasing concentrations
      of SAC (10-100 microM) were added to isolated brain synaptosomes at different
      times (1, 3 and 6 h) after the incubation with toxins (100 microM QUIN, 1 mM 3-NP
      or the combination of QUIN (21 microM) + 3-NP (166 microM). Thirty minutes later,
      lipid peroxidation (LP) and mitochondrial dysfunction (MD) were evaluated. For in
      vivo studies, SAC (100 mg/kg, i.p.) was given to QUIN- or 3-NP-striatally
      lesioned rats for 7 consecutive days (starting 120 min post-lesion). LP and MD
      were evaluated 7 days post-lesion in isolated striatal synaptosomes. Circling
      behavior was also assessed. Our results describe a differential pattern of
      protection achieved by SAC, mostly expressed in the 3-NP toxic model, in which
      nerve ending protection was found within the first hours (1 and 3) after the
      toxic insult started, supporting the concept that the ongoing oxidative damage
      and energy depletion can be treated during the first stages of neurotoxic events.

PMID- 19866341
TI  - Exploring the immune response against Mycobacterium tuberculosis for a better
      diagnosis of the infection.
AB  - Tuberculosis (TB) still represents a monumental problem, with more than two
      million deaths every year worldwide. The current diagnostics for TB offer sub
      optimal accuracy both for the active and the latent form of infection and are
      often based on technologies unaffordable in low-income settings. The tuberculin
      skin test was the first diagnostic based on an acquired immune response towards
      Mycobacterium tuberculosis (MTB). Advances in molecular and cellular biology and
      the elucidation of the mechanisms governing the relation between MTB and the
      human immune system form the basis for new and more accurate assays, potentially
      able to fill the gaps and limits of classical diagnostics. However, the process
      of validating new tests is still complex and hampered by specific questions
      regarding TB immunology and natural history. We present here a summary of the
      current approaches to validate new diagnostics based on the detection of
      immunological biomarkers of TB infection.

PMID- 19866342
TI  - Recent advances in multivalent self adjuvanting glycolipopeptide vaccine
      strategies against breast cancer.
AB  - Breast cancer (BrCa) is the second leading cause of cancer-related deaths for
      women worldwide. Evidence from both patients and mouse cancer models suggests
      that the simultaneous induction of BrCa-specific CD4(+) T cells, CD8(+) cytotoxic
      T cells, and antibodies is crucial for providing immune resistance. However,
      almost all current vaccines address only a single arm of the immune system, which
      may explain their lack of efficacy. We believe that the correct response to
      monovalent vaccines' "failure" is to increase our knowledge about antitumor
      protective immunity and to develop a multivalent vaccine molecule that can
      simultaneously induce multiple arms of the immune system. We highlight here
      recent advances in anti-BrCa peptide-based vaccine strategies with an emphasis on
      the self adjuvanting multivalent glycolipopeptide vaccine strategy recently
      developed in our laboratory and which showed promising results in both
      immunotherapeutic and immunoprophylactic settings.

PMID- 19866340
TI  - Cardiomyocyte death in doxorubicin-induced cardiotoxicity.
AB  - Doxorubicin (DOX) is one of the most widely used and successful antitumor drugs,
      but its cumulative and dose-dependent cardiac toxicity has been a major concern
      of oncologists in cancer therapeutic practice for decades. With the increasing
      population of cancer survivors, there is a growing need to develop preventive
      strategies and effective therapies against DOX-induced cardiotoxicity, in
      particular late-onset cardiomyopathy. Although intensive investigations on DOX
      induced cardiotoxicity have continued for decades, the underlying mechanisms
      responsible for DOX-induced cardiotoxicity have not been completely elucidated. A
      rapidly expanding body of evidence supports the notion that cardiomyocyte death
      by apoptosis and necrosis is a primary mechanism of DOX-induced cardiomyopathy
      and that other types of cell death, such as autophagy and senescence/aging, may
      participate in this process. This review focuses on the current understanding of
      the molecular mechanisms underlying DOX-induced cardiomyocyte death, including
      the major primary mechanism of excess production of reactive oxygen species (ROS)
      and other recently discovered ROS-independent mechanisms. The different
      sensitivities to DOX-induced cell death signals between adult and young
      cardiomyocytes will also be discussed.

PMID- 19866343
TI  - CD40-activated B cells from patients with systemic lupus erythematosus can be
      modulated by therapeutic immunoglobulins in vitro.
AB  - INTRODUCTION: Aberrant signaling within and between B and T cells, considered to
      be central in systemic lupus erythematosus (SLE), could depend on enhanced CD40
      CD154 activation. As a result, autoreactive B cells, normally anergic,
      differentiate and secrete antibodies attacking several normal tissues. Thus
      restorating B cell homeostasis might help control this disease. In this study,
      two facets of SLE B cells were investigated, namely their in vitro response to
      CD40-CD154 and the effect of treatment with human immunoglobulins for intravenous
      use (IVIg). MATERIALS AND METHODS: Blood samples from SLE patients and healthy
      volunteers were obtained and used to isolate B cells, which were activated
      through CD40 in the presence or absence of IVIg. The phenotype, proliferation,
      and differentiation of the SLE B cells were determined and compared with those of
      control B cells using flow cytometry and standard ELISA. RESULTS: In this model,
      CD40-activated SLE B cells, as control B cells, proliferated and differentiated
      and were characterized by the emergence of CD19(lo)CD38(++)CD138(+)CD27(++)
      cells. IVIg treatment of the CD40-activated SLE B cells resulted in higher
      differentiation, characterized by increased secretion rates of IgG and IgM, as
      reported previously for control B cells. CONCLUSIONS: Taken as a whole, such
      accelerated differentiation of CD40-activated B cells suggests that IVIg may
      participate in re-equilibration of the antibody repertoire by replacing
      pathological antibodies by de novo harmless antibodies.

PMID- 19866344
TI  - Complement: coming full circle.
AB  - The complement system has long been known to be a major element of innate
      immunity. Traditionally, it was regarded as the first line of defense against
      invading pathogens, leading to opsonization and phagocytosis or the direct lysis
      of microbes. However, from the second half of the twentieth century on, it became
      clear that complement is also intimately involved in the induction and "fine
      tuning" of adaptive B- and T-cell responses as well as lineage commitment. This
      growing recognition of the complement system's multifunctional role in immunity
      is consistent with the recent paradigm that complement is also necessary for the
      successful contraction of an adaptive immune response. This review aims at giving
      a condensed overview of complement's rise from a simple innate stop-and-go system
      to an essential and efficient participant in general immune homeostasis and
      acquired immunity.

PMID- 19866345
TI  - Stability validation of paraformaldehyde-fixed samples for the assessment of the
      platelet PECAM-1, P-selectin, and PAR-1 thrombin receptor by flow cytometry.
AB  - Sample fixation for storage and/or transportation represents an unsolved
      challenge for multicenter clinical trials assessing serial changes in platelet
      activity, or monitoring various antiplatelet regimens. Whole blood flow cytometry
      represents a major advance in defining platelet function, although special
      training and expensive equipment is required. We sought to determine how fixation
      with 2% paraformaldehyde (PFA), and storage of blood samples over 1 week affects
      the flow cytometry readings for both intact and thrombin-activating four major
      surface platelet receptors. Whole blood platelet expression of PECAM-1, P
      selectin, PAR-1 inactive receptor (SPAN-12), and cleaved (WEDE-15) epitope was
      assessed immediately after blood draw, after staining with 2% PFA, and at day 1,
      3, 5, and 7. The study was performed in 6 volunteers with multiple risk factors
      for vascular disease, not receiving any antiplatelet agents. Staining with PFA
      resulted in a slight decrease of fluorescence intensity, especially for PECAM-1,
      while antigen expression at day 1, 3 and 5 remains consistent, and highly
      reproducible. At day 7 there was a small but inconsistent trend towards
      diminished fluorescence intensity. The platelet data were consistent while
      validated with the isotype-matched irrelevant antibody. These data suggest that
      there is a 5 day window to perform final flow cytometry readings of whole blood
      PFA-fixed inactivated platelet samples. In contrast, thrombin activation cause
      gradual loss of flow cytometry signal, and cannot be recommended for long-term
      storage. This is critical logistic information for conducting multicenter
      platelet substudies within the framework of major clinical trials.

PMID- 19866346
TI  - Physico-chemical and in vitro biological evaluation of strontium/calcium
      silicophosphate glass.
AB  - Strontium is known to reduce bone resorption and stimulate bone formation.
      Incorporation of strontium into calcium phosphate bioceramics has been widely
      reported. In this work, calcium and calcium/strontium silicophosphate glasses
      were synthesized from the sol-gel process and their rheological, thermal, and in
      vitro biological properties were studied and compared to each other. The results
      showed that the gel viscosity and thus the rate of gel formation increased by
      using strontium in glass composition and by increasing aging temperature. In
      strontium-containing glass, the crystallization temperature increased and the
      type of the crystallized phase was different to that of strontium-free glass.
      Both glasses favored precipitation of calcium phosphate layer when they were
      soaked in simulated body fluid; however strontium seemed to retard the rate of
      precipitation slightly. The in vitro biodegradation rate of the strontium/calcium
      silicophosphate glass was higher than that of strontium-free one. The cell
      culture experiments carried out using rat calvaria osteoblasts showed that the
      incorporation of strontium into the glass composition stimulated proliferation of
      the cells and enhanced their alkaline phosphatase activity, depending on cell
      culture period.

PMID- 19866347
TI  - Lifestyle-related determinants of hookah and cigarette smoking in Iranian adults.
AB  - To identify lifestyle-related determinants of hookah and cigarette smoking in
      Iranian adults, a total of 12,514 men and women aged >/=19 years in three
      counties in central Iran (Isfahan, Najafabad, Arak) were selected in multistage
      random sampling. Data on socio-demographic characteristics and lifestyle were
      collected in interviewer-administered questionnaires, as part of the baseline
      survey of the Isfahan Healthy Heart Program. Unhealthy lifestyle-related factors
      independently associated with cigarette and hookah smoking, were identified in
      sex-specific multivariate logistic regression analyses. High stress levels (OR:
      1.55; 95% CI: 1.35-1.78 for men; OR: 1.63; 95% CI: 1.17-2.27 for women), family
      member smoking (OR: 1.61; 95% CI: 1.27-4.92 for men; OR: 2.49; 95% CI: 2.20-2.95
      for women), and short/long sleep duration (OR: 1.18; 95% CI: 1.01-1.39 for men;
      OR: 1.52; 95% CI: 1.10-2.35 for women) were associated with cigarette smoking in
      both men and women. Poor diet was also related to cigarette smoking in men (OR:
      1.55; 95% CI: 1.62-1.89). Family member smoking was associated with hookah
      smoking in both men (OR: 1.16; 95% CI: 1.05-3.12) and women (OR: 1.56; 95% CI:
      1.02-4.92), and in addition high stress levels (OR: 2.87; 95% CI: 1.14-5.83) and
      short/long sleep duration (OR: 1.07; 95% CI: 1.02-2.41) were associated with
      hookah smoking in women. Unhealthy lifestyle-related factors co-occur with
      cigarette and hookah smoking in Iranian adults, likely increasing the risk for
      chronic health problems. Sex differences in the determinants of hookah and
      cigarette smoking may need to be taken into account in planning tobacco control
      strategies.

PMID- 19866348
TI  - Conceptual and measurement issues in early parenting practices research: an
      epidemiologic perspective.
AB  - Early parenting practices are significant to public health because of their
      linkages to child health outcomes. This paper focuses on the current state of the
      science regarding conceptual frameworks that incorporate early parenting
      practices in epidemiologic research and evidence supporting reliability and
      validity of self-report measures of such practices. Guided by a provisional
      definition of early parenting practices, literature searches were conducted using
      PubMed and Sociological Abstracts. Twenty-five published studies that included
      parent-report measures of early parenting practices met inclusion criteria.
      Findings on conceptual frameworks were analyzed qualitatively, whereas evidence
      of reliability and validity were organized into four domains (safety, feeding and
      oral health, development promotion, and discipline) and summarized in tabular
      form. Quantitative estimates of measures of reliability and validity were
      extracted, where available. We found two frameworks incorporating early
      parenting: one a program theory and the other a predictive model. We found no
      reported evidence of the reliability or validity of parent-report measures of
      safety or feeding and oral health practices. Evidence for reliability and
      validity were reported with greater frequency for development promotion and
      discipline practices, but report of the most pertinent type of reliability
      estimation, test-retest reliability, was rare. Failure to examine associations of
      early parenting practices with any child outcomes within most studies resulted in
      missed opportunities to indirectly estimate validity of parenting practice
      measures. Stronger evidence concerning specific measurement properties of early
      parenting practices is important to advancing maternal-child research,
      surveillance, and practice.

PMID- 19866349
TI  - Anatomical analysis of recurrent conduction after circumferential ablation.
AB  - INTRODUCTION: There is general agreement on the importance of electrical
      isolation of antral (including pulmonary vein) myocardium for effective atrial
      fibrillation (AF) ablation. However, isolation is often impermanent, and return
      of conduction (RoC) is associated with recrudescent AF. It is generally assumed
      that the mechanism of RoC is recovery of ablated myocardium, but this is based
      almost solely on experience after ablation at the venoatrial junctions. Our
      objective was to perform an anatomical analysis as a means to gain further
      insight into RoC risk factors and mechanism(s) after wide-area circumferential
      ablation. METHODS: Retrospective review of data from 512 consecutive patients who
      underwent wide-area circumferential antral ablation. After achieving left and
      right antral electrical isolation, each patient underwent a period of observation
      for RoC during this initial procedure. In addition, 76 of the 512 patients
      underwent a repeat procedure at an average of 10 months later, at which time they
      were again assayed for RoC. RESULTS: Left or right antral RoC was observed in 39
      (8%) or 21 (4%) patients, respectively, during the initial procedure, and 26
      (34%) or 16 (21%) patients, respectively, during the repeat procedure. Left
      antral RoC was more commonly observed among patients manifesting a long segment
      separating the circumferential lesion and the venoatrial junctions, and usually
      occurred in this segment, often at sites distant from ablated sites. Right antral
      RoC commonly occurred in the anterior and superior antral regions, also often at
      sites that were distant from ablated sites. CONCLUSIONS: In the left antrum,
      there was a correlation between electrophysiologic (RoC) and anatomic (long
      segment) properties. The observation in both antra that RoC often occurred in
      previously unablated areas suggested that, as an alternative to recovery of
      ablated myocardium, a second mechanism of RoC was plausible: conduction via
      unablated myocardium, which was not immediately manifest. These observations have
      compelled us to modify our circumferential lesion.

PMID- 19866350
TI  - Activation mapping of focal atrial tachycardia: the impact of the method for
      estimating activation time.
AB  - PURPOSE: Different methods can be used to estimate activation time during the
      mapping of focal atrial tachycardia. The present study aimed to compare
      activation maps generated by three widely used methods of determining activation
      time. METHODS: Fourteen patients (mean age 48 +/- 17 years) with focal atrial
      tachycardia were investigated. Mapping was performed with the CARTO system. All
      patients underwent successful ablation. Local activation time was successively
      defined as the peak amplitude (Bi-peak), the steepest downslope (Bi-dslope), and
      the onset (Bi-on) of the bipolar electrograms. RESULTS: The three methods of
      activation time determination were highly correlated with one another but
      generated foci with different locations. The distances between the foci generated
      by the different methods were 4.36 +/- 4.91 mm (Bi-peak-Bi-dslope), 7.21 +/- 5.11
      mm (Bi-peak-Bi-on), and 7.21 +/- 5.87 mm (Bi-dslope-Bi-on) (p = 0.26). Also, the
      three methods generated foci with different diameters: 3.13 +/- 2.17 mm for Bi
      peak, 2.81 +/- 0.78 for Bi-dslope, and 2.54 +/- 0.14 mm for Bi-on (p = 0.60).
      However, the foci tended to cluster within relatively wide regions of low
      amplitude fractionated electrograms. The surface of these regions was 3.81 +/-
      2.34 cm(2) (Bi-peak), 3.38 +/- 2.12 cm(2) (Bi-dslope), and 4.76 +/- 3.01 cm(2)
      (Bi-on) (p = 0.34). CONCLUSION: The three methods of activation time
      determination, although highly correlated with one another, may generate foci of
      different sizes and in different locations. However, the foci tend to cluster
      within relatively large areas of low-amplitude fractionated electrograms. These
      findings suggest a sizeable atrial region with particular electrophysiological
      proprieties and raise the possibility of an anatomical substrate of the
      tachycardia. During mapping, this region can be roughly delineated by all three
      methods of activation time estimation. However, details concerning the activation
      pattern within the region and the location of the focus vary among the methods.

PMID- 19866351
TI  - Spatially structured oscillations in a two-dimensional excitatory neuronal
      network with synaptic depression.
AB  - We study the spatiotemporal dynamics of a two-dimensional excitatory neuronal
      network with synaptic depression. Coupling between populations of neurons is
      taken to be nonlocal, while depression is taken to be local and presynaptic. We
      show that the network supports a wide range of spatially structured oscillations,
      which are suggestive of phenomena seen in cortical slice experiments and in vivo.
      The particular form of the oscillations depends on initial conditions and the
      level of background noise. Given an initial, spatially localized stimulus,
      activity evolves to a spatially localized oscillating core that periodically
      emits target waves. Low levels of noise can spontaneously generate several
      pockets of oscillatory activity that interact via their target patterns. Periodic
      activity in space can also organize into spiral waves, provided that there is
      some source of rotational symmetry breaking due to external stimuli or noise. In
      the high gain limit, no oscillatory behavior exists, but a transient stimulus can
      lead to a single, outward propagating target wave.

PMID- 19866352
TI  - Models of cortical networks with long-range patchy projections.
AB  - The cortex exhibits an intricate vertical and horizontal architecture, the latter
      often featuring spatially clustered projection patterns, so-called patches. Many
      network studies of cortical dynamics ignore such spatial structures and assume
      purely random wiring. Here, we focus on non-random network structures provided by
      long-range horizontal (patchy) connections that remain inside the gray matter. We
      investigate how the spatial arrangement of patchy projections influences global
      network topology and predict its impact on the activity dynamics of the network.
      Since neuroanatomical data on horizontal projections is rather sparse, we suggest
      and compare four candidate scenarios of how patchy connections may be
      established. To identify a set of characteristic network properties that enables
      us to pin down the differences between the resulting network models, we employ
      the framework of stochastic graph theory. We find that patchy projections provide
      an exceptionally efficient way of wiring, as the resulting networks tend to
      exhibit small-world properties with significantly reduced wiring costs.
      Furthermore, the eigenvalue spectra, as well as the structure of common in- and
      output of the networks suggest that different spatial connectivity patterns
      support distinct types of activity propagation.

PMID- 19866353
TI  - Mixed infection in tomato to ensure frequent generation of a natural reassortant
      between two subgroups of Cucumber mosaic virus.
AB  - Cucumber mosaic virus (CMV) is divided into subgroups I (sub-I) and II (sub-II).
      Isolate CMV-PF, which had been isolated from tomato by single lesion isolation
      (SLI), was classified in sub-II by serology, but it had the pathogenicity of sub
      I CMVs. Sequence comparisons and phylogenetic analyses showed that CMV-PF was
      actually a reassortant CMV isolate containing RNAs 1 and 2 from sub-I and RNA 3
      from sub-II (I, I, and II). A subgroup-specific reverse transcription-polymerase
      chain reaction (SS-RT-PCR) was devised to detect reassortants between sub-I and
      sub-II. Six primer sets specific to genomic RNAs were designed for each subgroup,
      and those primer sets successfully amplified their target RT-PCR products. Of 38
      natural CMV isolates, two isolates (nos. 9-7 and 27-3) contained mixed RNAs of
      both subgroups. SLI-progenies of 9-7 were subsequently isolated by SLI using
      Vigna unguiculata and analyzed by SS-RT-PCR; they were found to be a reassortant
      containing RNAs 1 and 2 from sub-I and RNA 3 from sub-II (I, I, and II). Although
      natural reassortants between CMV subgroups were thought to be infrequent based on
      previous observations, we readily found two isolates of a reassortant (I, I, and
      II) in different tomato fields, implying that tomato may act as a reservoir of
      mixed infection in the generation of a CMV reassortant perhaps by aphids.

PMID- 19866354
TI  - The mathematics of concurrent partnerships and HIV: a commentary on Lurie and
      Rosenthal, 2009.

PMID- 19866355
TI  - Evaluation of in vitro fertilization parameters and estrogen receptor alpha gene
      polymorphisms for women with unexplained infertility.
AB  - PURPOSE: Association of ESR1 gene PvuII, XbaI and (TA)n microsatellite
      polymorphisms and woman infertility was evaluated. METHODS: Infertile(n = 104)
      and fertile(n = 107) women were included in this study. We performed polymerase
      chain reaction-restriction fragment-length polymorphism analysis for detecting
      ESR1 polymorphisms. RESULT(S): PvuII and XbaI polymorphisms confered risk for
      infertility in a simple dominant manner in which a significant relationship was
      observed between infertile and control women. Infertile women had fewer(<18)
      short repeat alleles in promotor region. ESR1 genotypes were compared concerning
      maturation, fertilization, pregnancy rates and embryo quality. Although no
      difference was found in terms of pregnancy rates, maturation and fertilization
      rates were significantly smaller in pp and xx genotypes. Also, pp genotypes had
      significantly lower number of good quality embryos. Long TA repeat in promotor
      was found to be associated with low fertilization rate. CONCLUSION(S):
      Polymorphisms at the ESR1 gene are associated with infertility in this Turkish
      infertile women population.

PMID- 19866356
TI  - Sensitivity analyses including and excluding the HWE-violating studies are
      required for meta-analyses of genetic association studies.

PMID- 19866358
TI  - Non-organizational religious participation, subjective religiosity, and
      spirituality among older African Americans and Black Caribbeans.
AB  - This study utilizes data from the National Survey of American Life to examine the
      sociodemographic and denominational correlates of religious involvement and
      spirituality among older African Americans and Black Caribbeans. Eleven measures
      of non-organizational religious participation, subjective religiosity, and
      spirituality are utilized. The findings indicate significant gender, income,
      region, marital status, denominational, and immigration status differences in
      religiosity and spirituality. Among older Black Caribbeans, income was a
      consistent correlate of religious participation and spirituality. The findings
      are discussed in relation to prior work in the area of religious involvement
      among older adults.

PMID- 19866359
TI  - Polyphenolic composition and antioxidant characteristics of kumquat (Fortunella
      margarita) peel fractions.
AB  - The polyphenolic composition of two Fortunella margarita (Nagami kumquat)
      specimens from Greece and Egypt was investigated employing fractionation by
      solvent partition and liquid chromatography-mass spectrometry. The main groups of
      phenolics identified in the different fractions generated were C-glycosylated
      flavones, O-glycosylated flavones, C-glycosylated flavanones, O-glycosylated
      flavanones, flavonols, chalcones, phenolic acids and derivatives thereof. The
      antioxidant potency of the fractions was assessed using two representative in
      vitro tests, including antiradical activity and hydroxyl free radical scavenging
      activity. It was revealed that the ethyl acetate fractions from both specimens
      contained the higher polyphenol content and exhibited the better antioxidant
      characteristics. The results indicated that F. margarita peels may be regarded as
      a rich source of potentially bioactive polyphenols.

PMID- 19866357
TI  - Do we have two hearts? New insights in right ventricular function supported by
      myocardial imaging echocardiography.
AB  - RV performance is difficult to evaluate, given its geometry, interrelationship
      with the left ventricle, and sensitivity to alterations in pulmonary pressure.
      This article focuses on some of the challenges related to the assessment of RV
      function in the setting of the RV's unique anatomic, physiologic, conventional
      and newer echocardiographic aspects, and therapeutic implications. The majority
      of proposed methods of echocardiographic assessment of RV function are based on
      volumetric approximations of the RV. Such approaches have inherent limitations,
      first as volume-related measures such as EF are load dependent, second because of
      the complex geometry of the RV. The issue of RV geometry is usually overcome
      using geometry-independent parameters such as tricuspid annular excursion and the
      Tei index. The recent introduction of real-time three-dimensional
      echocardiography and myocardial imaging echocardiography (tissue Doppler imaging,
      1D-strain and 2D-strain echocardiography) implied a great progress in
      echocardiography. Tissue Doppler imaging allows the quantitative assessment of RV
      systolic and diastolic function by means of measurement of myocardial velocities.
      Strain measurements have been shown to correlate well with sonomicrometry segment
      length measurements both in the inflow and outflow tract of the RV and under
      different loading conditions. Other findings have been reported in chronic and
      acute clinical settings. Standard and novel echocardiographic methods of
      assessment of RV size and performance can help clinicians in the treatment of
      acute and chronic RV failure and contribute to a better understanding of the
      peculiar chamber-related functional mechanisms in the context of ventricular
      interdependent independency.

PMID- 19866360
TI  - A comparison of tobacco-related risk factors between preadolescents with and
      without cancer.
AB  - INTRODUCTION: To compare preadolescents with and without cancer on current
      smoking status, future intentions to smoke, and tobacco-related risk factors, as
      well as to explore the relationship between cancer status and tobacco-related
      variables with intentions. PROCEDURE: Ninety-four preadolescents undergoing
      treatment for cancer and a matched comparison sample of 190 participants without
      cancer, ages 8 to 11 years, completed questionnaires about their smoking habits,
      intentions to smoke and tobacco-related psychosocial risk factors. RESULTS: No
      preadolescents with cancer and only two preadolescents without cancer reported
      current smoking. Compared to healthy nonsmoking preadolescents, nonsmokers with
      cancer were approximately one-half as likely to report future intentions to
      smoke. Intention to smoke was better predicted by variables most proximal to
      smoking including older age, being male, not having cancer, having close friends
      who smoke, parental smoking, and lower perceived vulnerability for tobacco
      related illnesses. In the model examining distal variables, preadolescents who
      were more rebellious, older, and without cancer were more likely to report future
      smoking intentions. DISCUSSION/CONCLUSIONS: Although future intentions to smoke
      differed according to cancer status, the relationship between tobacco-related
      risk factors and future smoking intentions appeared to be similar among
      preadolescents with and without cancer. IMPLICATIONS FOR CANCER SURVIVORS:
      Smoking prevention and tobacco-related health risk education should begin during
      the elementary years, a time prior to smoking initiation and the development of
      solidified smoking attitudes. The diagnosis and treatment of pediatric cancer may
      provide an excellent opportunity for health care providers to begin communicating
      anti-smoking messages and health risk counseling to their young patients and
      families.

PMID- 19866361
TI  - Surfactant-free formulation of poly(lactic/glycolic) acid nanoparticles
      encapsulating functional polypeptide: a technical note.

PMID- 19866362
TI  - Effect of particle shape on dry particle inhalation: study of flowability,
      aerosolization, and deposition properties.
AB  - The shape effects of dry particles on flowability, aerosolization, and deposition
      properties in inhalation drug delivery are studied. The properties are compared
      with similar size range particles of different shapes such as sphere, needle,
      cube, plate, and pollen. Flowability of the particles is characterized by Carr's
      compressibility index and angle of slide (theta) method. The aerosolization and
      deposition properties of the particles are studied in vitro using an eight-stage
      Anderson cascade impactor with a Rotahaler. Pollen-shaped particles are found to
      exhibit better flowability, higher emitted dose, and higher fine particle
      fraction than particles of other shapes in similar size range. They showed
      minimum theta of 35 degrees and maximum emitted dose of 87% and fine particle
      fraction of 16%. The use of pollen-shaped particles can be a potential
      improvement in dry particle inhalation.

PMID- 19866363
TI  - Increasing trend of the incidence of esophageal squamous cell carcinoma, but not
      adenocarcinoma, in Taiwan.
AB  - Epidemiologic data on esophageal cancer in Asia are extremely limited. We
      examined temporal trends in the incidence of esophageal squamous cell carcinoma
      (ESCC) and esophageal adenocarcinoma (EA) in Taiwan. Patients with esophageal
      cancer were identified from the Taiwan Cancer Registry between 1979 and 2003. Age
      standardized incidences of ESCC and EA were calculated based on the national
      census and world standard population. Trends in incidence rates were estimated by
      calculating the annual percentage change (APC). The age-standardized incidence of
      ESCC increased progressively (from 1979-1983 to 1999-2003: 2.63 to 4.37 per
      100,000-year), with an APC higher in male (3.27%, P < 0.0001) than that in female
      (1.23%, P = 0.03). Though the crude incidence of EA progressively increased in
      both gender (male: 0.28-0.49 per 100,000-year; female 0.07-0.11 per 100,000
      year), the age-standardized incidence of EA is similar along the study period
      with an APC of 0.72% (P = 0.20) in male and 1.59% (P = 0.30) in female. In
      Taiwan, the incidence of ESCC significantly increased from 1979 to 2003, whereas
      the incidence of EA remained unchanged. Although EA incidence has not recently
      increased, it could in the future.

PMID- 19866364
TI  - Characteristics of PAHs adsorbed on street dust and the correlation with specific
      surface area and TOC.
AB  - Street dust was collected from five roads with different traffic volumes in the
      metropolitan area of Beijing and separated into five size fractions.
      Concentrations of polycyclic aromatic hydrocarbons (PAHs) adsorbed on street dust
      in different size ranges and their correlation with specific surface area and
      total organic carbon (TOC) were investigated. Results show that the concentration
      of 16-PAHs of sieved samples ranges from 0.27 to 1.30 mg/kg for all the sampling
      sites. Particles smaller than 40 mum in diameter have the highest 16-PAHs
      concentration among all of the size ranges for street dust from the four sampling
      sites with vehicles running on. PAHs with three or four rings account for 68% of
      the overall 16-PAHs on average. Remarkable positive correlation exists between 16
      PAHs concentration and specific surface area with R(2) values from 0.7 to 0.96
      for the four sampling sites with vehicles running on. The relationship between
      the concentration of 16-PAHs and TOC is less clear.

PMID- 19866365
TI  - Measurement of soil radioactivity levels and radiation hazard assessment in
      southern Rechna interfluvial region, Pakistan.
AB  - Rechna interfluvial region is one of the main regions of Punjab, Pakistan. It is
      the area which is lying between River Ravi and River Chenab, alluvial-filled.
      Radioactivity levels in soil samples, collected from southern Rechna interfluvial
      region, Pakistan, have been estimated by using gamma-ray spectrometric technique.
      (226)Ra, (232)Th, the primordial radionuclide (40)K, and the artificial
      radionuclide (137)Cs have been measured in the soil of the study area. The mean
      radioactivity levels of (226)Ra, (232)Th, (40)K, and (137)Cs were found to be
      50.6 +/- 1.7, 62.3 +/- 3.2, 662.2 +/- 32.1, and 3.1 +/- 0.3 Bq kg(-1),
      respectively. The mean radium equivalent activity (Ra(eq)), outdoor radiation
      hazard index (H(out)), indoor radiation hazard index (H(in)), and terrestrial
      absorbed dose rate for the area under study were determined as 190.8 +/- 8.7 Bq
      kg(-1), 0.52, 0.65, and 69.8 nGy h(-1), respectively. The annual effective dose
      to the general public was found to be 0.43 mSv. This value lies well below the
      limit of 1 mSv for general public as recommended by the International Commission
      on Radiological Protection. The measured values are comparable with other global
      radioactivity measurements and are found to be safe for the public and the
      environment.

PMID- 19866366
TI  - Aluminum-induced oxidative stress in lymphocytes of common carp (Cyprinus
      carpio).
AB  - Several studies of fish have shown that aluminum may induce hypoxia, hypercapnia,
      metabolic acidosis, and respiratory failure. In lymphocytes, morphologic
      abnormalities and reduced immune activity have been observed. Nevertheless, there
      is little data on oxidative stress and such data are essential in order to
      identify its mechanism of action. The common carp Cyprinus carpio, an omnivorous
      fish commonly used in commercial aquaculture, has been proposed as a test
      organism in toxicologic assays due to its economic importance and wide geographic
      distribution. The aim of this work was to evaluate Al-induced oxidative stress in
      lymphocytes of the common carp C. carpio. Specimens were exposed to three
      different concentrations of Al (0.05, 120, and 239 mg/l) in a static exposure
      system for 96 h. At the end of the exposure period, blood was collected and
      lymphocytes were separated. Lipid peroxidation, oxidized protein content and the
      activity of superoxide dismutase, catalase, and glutathione peroxidase were
      measured. Results show that the tested Al concentrations modified the activity of
      antioxidant enzymes and elicited higher levels of lipid peroxidation and oxidized
      proteins. The degree of damage induced was concentration and tissue dependent.

PMID- 19866368
TI  - Effects of different levels of dried sweet potato (Ipomoea batatas) leaves
      inclusion in finisher ration on feed intake, growth, and carcass yield
      performance of Ross broiler chicks.
AB  - The effect of supplementation with increasing levels of dried leaves of sweet
      potato (Ipomoea batatas) on feed intake, body weight gain, and carcass yield
      characteristics of finisher Ross broiler chicks was studied at Haramaya
      University, Ethiopia. Three hundred Ross broiler chicks aging 29 days and
      weighing 540 +/- 5.28 g (mean +/- SD) were randomly distributed to 15 pens, each
      with 20 chicks, representing five treatment rations each with three replications.
      Dietary treatments consisted of inclusions of dried leaves of sweet potato at
      levels of 0, 50, 100, 150, and 200 g/kg DM for treatments T1, T2, T3, T4, and T5,
      respectively. The experiment lasted for 28 days, during which, dry matter intake
      (DMI), body weight gain, and feed conversion efficiency; carcass yield
      characteristics; and weights and lengths of different parts of gastrointestinal
      tract were measured. Data were subjected to statistical analysis using SAS
      (1998). Inclusion of dried leaves of sweet potato at the level of 200 g/kg DM
      resulted in lower (P < 0.01) daily DMI as compared to chicks in control diet
      (T1). The daily body weight gain declined (P < 0.01) when the level of dried
      leaves of sweet potato in the diet was 150 and 200 g/kg DM. Inclusion of dried
      leaves of sweet potato up to 100 g/kg DM did not affect (P > 0.05) eviscerated
      carcass weight, and weights of drumstick with thigh and breast meat were not
      affected (P > 0.05) by inclusion of dried leaves of sweet potato up to 150 g/kg
      DM. The results of this study revealed that inclusion of dried leaves of sweet
      potato up to 100 g/kg DM in the finisher ration might be considered as the
      optimum level of supplementation when chickens are sold on live weight basis, but
      if birds are sold on eviscerated carcass weight basis, inclusion up to 150 g/kg
      DM might be economically feasible as it produced higher carcass yield components.

PMID- 19866367
TI  - Wells-Dawson heteropolyacid supported on silica: a highly efficient catalyst for
      synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles.
AB  - Heteropolyacid H(6)P(2)W(18)O(62).24H(2)O (WD) supported on silica (WD/SiO(2))
      has been used as an effective catalytic system for the synthesis of various
      1,2,4,5-tetrasubstituted imidazoles by four-component condensation of benzil,
      aldehydes, amines and ammonium acetate under solvent-free conditions. This
      approach can be useful for three-component synthesis of 2,4,5-trisubstituted
      imidazoles. The same reactions were repeated by using benzoin instead of benzil.

PMID- 19866369
TI  - Presenting manifestations of eosinophilic cystitis in two Filipino children.
AB  - Eosinophilic cystitis is a very rare clinical disease entity in the pediatric
      population. We report two cases of Filipino children with eosinophilic cystitis
      who presented with irritative voiding symptoms, gross hematuria, peripheral
      eosinophilia, and hydroureteronephrosis and urinary bladder wall thickening
      visualized on ultrasonography and CT urography. Cystoscopy and transurethral
      biopsy confirmed the diagnosis. Both patients were started with corticosteroid
      with or without an antihistamine. Resolution from the signs and symptoms were
      observed in both patients as documented by disappearance of peripheral
      eosinophilia, normal urinalysis results, and resolution of the
      hydroureteronephrosis and urinary bladder wall thickening on ultrasonography on
      follow-up.

PMID- 19866370
TI  - A pure primary low-grade neuroendocrine carcinoma (carcinoid tumor) of the
      prostate.
AB  - The first time in Scandinavia we present a case report of a pure primary low
      grade neuroendocrine carcinoma (carcinoid tumor) of the prostate. Our patient is
      a 34-year-old male with a long history of symptomatic chronic
      prostatitis/prostatodynia. After developing severe obstructive uropathy, a
      transurethral resection was performed. An unexpected diagnosis of a low-grade
      neuroendocrine carcinoma was made. Subsequently, in radical
      prostatovesiculectomy, we noted metastases to both seminal vesicles and two
      inguinal lymph nodes. Follow up is ongoing.

PMID- 19866371
TI  - Comparison of the differences in circadian autonomic function in hyperlipidemic
      men with and without erectile dysfunction.
AB  - BACKGROUND: We aimed to investigate differences in circadian autonomic changes in
      patients suffering from hyperlipidemia with and without erectile dysfunction and
      compared results to control cases. MATERIALS AND METHODS: A total of 77 patients
      (age range: 24-74, mean age: 45.3 +/- 9.3) with uncontrolled hyperlipidemia
      (total cholesterol >200 mg/dL and/or LDL >160 mg/dL despite a regular diet) were
      enrolled into the study. These patients were divided into two groups according to
      their International Index of Erectile Function (IIEF-EF) scores as having
      erectile dysfunction (IIEF-EF < 26) (Group 1) or as having normal erectile
      function (IIEF-EF >= 26) (Group 2). In addition, the control group comprised 44
      healthy men (age range: 20-57, mean age: 44.0 +/- 10.8) (Group 3). Heart rate
      variability parameters obtained by 24-h Holter monitoring were utilized for the
      indirect evaluation of autonomic function. RESULTS: There were statistically
      significant differences between the groups with respect to daytime and nocturnal
      autonomic activity (p < 0.005). Moreover, Group 1 had lower nocturnal
      parasympathetic and higher nocturnal sympathetic activity compared to the other
      groups (for nocturnal HFn p(1-2) < 0.001; p(1-3) < 0.001; p(2-3) > 0.05; for
      nocturnal LFn p(1-2) < 0.001; p(1-3) < 0.001; p(2-3) > 0.05). CONCLUSION: We
      concluded that hyperlipidemia results in deterioration of autonomic circadian
      rhythm. Hyperlipidemic patients with erectile dysfunction had diminished
      nocturnal parasympathetic activities.

PMID- 19866372
TI  - Urethral stricture Yemen experience.
AB  - PURPOSE: In order to evaluate the etiology of urethral stricture in our society
      and outcome of different types of surgical reconstruction used to treat them.
      PATIENTS AND METHODS: This prospective study was carried out in the Urology and
      Nephrology Center, at Al-Thawra Modern General and Teaching Hospital, Sana'a,
      Yemen from July 2003 to July 2007 and included 62 male patients with complete
      urethral stricture whom underwent Urethral reconstructive surgery. The patients
      were evaluated by history, local and systemic physical examination, and
      radiological assessment according to each case. RESULTS: Patient's age ranged
      between 3 and 70 years (mean 25.31). Of 55 patients presented to the GER, 31
      patients had car accident, 14 patients had gun shot injury, 9 patients fell from
      high, and one patient had bomb explosion. Five patients had history of
      traumatized catheterization and urethrocystoscopy, while two patients had history
      of urethritis. The site of the stricture was at the bulbomembranous area in 43
      patients, in the penile urethra in 14 patients, and in bulbous urethra in 5
      patients. The length of the urethral stricture was 10-30 mm in 39 patients (63%),
      <10 mm in 13 patients (21%) and of 30-70 mm in 10 patients (16%). A total of 15
      patients (24%) with posterior urethral stricture of 10 mm or less (+2 patients
      with 1.2 and 1.5 cm), subjected to endoscopic treatment, 37 patients (60%) with
      stricture >10-30 mm, were underwent anastomotic urethral reconstruction and 10
      patients (15%) with stricture >30 mm, were repaired utilizing tissue transfer
      technique. Follow-up period ranged from 3 months to 2 years (median 15 months),
      in which recurrent stricture was found in 11 patients (18%), wound dehiscence in
      4 patients (6%) and fistula formation in 1 patient (1.5%), while no patient came
      with erectile dysfunction. CONCLUSION: Trauma is the commonest cause of urethral
      stricture in our country, therefore the control of it will decrease extremely the
      urethral stricture disease. No one technique is suitable for all types of the
      stricture, and the surgeon should be familiar with the different techniques and
      choose the most suitable one according to the case he deals with.

PMID- 19866373
TI  - Genetic diversity of phthalic acid esters-degrading bacteria isolated from
      different geographical regions of China.
AB  - Thirty-two strains of phthalic acid ester (PAEs)-degrading bacteria were isolated
      from thirteen geographically diverse sites by enrichment using mixtures of PAEs
      as the sole source of carbon and energy. Sequence analyses of the 16S rRNA gene
      indicated that these isolates were from six genera (Arthrobacter, Gordonia,
      Rhodococcus, Acinetobacter, Pseudomonas, and Delftia). To evaluate the genetic
      diversity among them, the molecular typing method rep-PCR with primers based on
      enterobacterial repetitive intergenic consensus, repetitive extragenic
      palindromes, and BOXAIR sequences was performed. Strain-specific and unique
      genotypic fingerprints were distinguished for most of these isolates. In
      addition, utilization of various PAEs and the central intermediate phthalic acid
      by representative isolates suggested inter-isolate differences in the substrate
      utilization and degradation pathways. Furthermore, HPLC analysis showed that the
      rate of dimethyl phthalate degradation varied from 48.32 to 100% between strains.
      These results suggest a high level of genetic diversity among PAEs-degrading
      bacteria in the natural environment and their great potential to clean up
      phthalates-contaminated environments.

PMID- 19866374
TI  - A black mobile mass: diagnosis and management.
AB  - The diagnosis and treatment of left ventricular apical thrombi after myocardial
      infarction are still not well established. Fibrinolytic treatment, heparin
      treatment and surgical removal might be therapeutic options. We present the case
      of a 37 year old man who came into the Emergency department complaining of
      pleuritic chest pain. ECG revealed an evolving anterior wall infarction and
      transthoracic echocardiogram showed a big mobile thrombus in the ventricular
      apex. In order to confirm diagnosis and to differentiate other entities like
      pseudoaneurysm, contrast echocardiography and cardiac MRI with late gadolinium
      enhancement were performed and allowed a definitive diagnosis. Our patient was
      treated with intravenous heparin and then with oral anticoagulation. Two months
      later, echocardiogram showed an apical non-mobile and smaller thrombus.

PMID- 19866376
TI  - Analysis of carbon metabolism and improvement of gamma-polyglutamic acid
      production from Bacillus subtilis NX-2.
AB  - Bacillus subtilis NX-2 produces gamma-polyglutamic acid (gamma-PGA) when using
      glucose and L-glutamate as carbon sources. The conversion of carbon sources into
      gamma-PGA was analyzed with the (13)C-NMR method after enriching the media with
      (13)C-labeled glucose. The results showed that the percentage of gamma-PGA
      monomers derived from glucose was relatively low, approximately 6% and 9%,
      respectively, with an initial glucose concentration of 30 and 40 g L(-1). It was
      concluded that glucose was utilized mainly as the growth-limiting substrate for
      cell growth and supplied the required energy during gamma-PGA biosynthesis, while
      L-glutamate was preferred as the main substrate for gamma-PGA formation. To
      achieve an efficient conversion of L-glutamate and enhance the gamma-PGA
      production, a fed-batch culture was proposed by feeding of glucose. By this
      method, supplied L-glutamate (40 g L(-1)) was completely depleted, and gamma-PGA
      yield was attained 42 g L(-1).

PMID- 19866379
TI  - Student projects in medicine: a lesson in science and ethics.
AB  - Regulation of biomedical research is the subject of considerable debate in the
      bioethics and health policy worlds. The ethics and governance of medical student
      projects is becoming an increasingly important topic in its own right, especially
      in the U.K., where there are periodic calls to change it. My main claim is that
      there seems to be no good reason for treating student projects differently from
      projects led by qualified and more experienced scientists and hence no good
      grounds for changing the current system of ethics review. I first suggest that
      the educational objectives cannot be met without laying down standards of good
      science, whatever they may be. Weak science is unnecessary for educational
      purposes, and it is, in any case, unlikely to produce good researchers in the
      future. Furthermore, it is curious to want to change the system of ethics review
      specifically for students when it is the science that is at stake, and when the
      science now falls largely outside the ethics remit. I further show that ethics
      review is nevertheless important since students carry a new potential conflict of
      interests that warrants independent oversight which supervisory support does not
      offer. This potential conflict may become more morally troublesome the greater
      the risks to the subjects of the research, and students may impose greater risks
      on their subjects (relative to professional researchers) by virtue of being
      inexperienced, whatever the nature of the project. Pragmatic concerns may finally
      be allayed by organizing the current system more efficiently at critical times of
      the university calendar.

PMID- 19866380
TI  - Dealing with misconduct in biomedical research: a review of the problems and the
      proposed methods for improvement.
AB  - The increasing complexity of scientific research has been followed by increasing
      varieties of research misconduct. Dealing with misconduct involves the processes
      of detection, reporting, and investigation of misconduct. Each of these steps is
      associated with numerous problems which need to be addressed. Misconduct
      investigation should not stop with inquiries and disciplinary actions in specific
      episodes of misconduct. It is necessary to decrease the personal price paid by
      those who expose misconduct and to protect the personal and professional
      interests of honest researchers accused of misconduct unfairly or mistakenly.
      There is no dearth of suggestions to improve the objectivity and fairness of
      investigations. What is needed is the willingness to test the various options and
      implement the most suitable ones.

PMID- 19866377
TI  - Toll-like receptors in pregnancy disorders and placental dysfunction.
AB  - The Toll receptor was originally identified as a regulator of embryogenesis in
      Drosophila. Toll-like receptors (TLRs) in mammals recognize infectious agents and
      other danger signals. Activation of TLRs on trophoblast influences immune cell
      recruitment, cytokine secretion, and decidual responses to invading pathogens
      during pregnancy. Importantly, biological effects of TLR signal transduction at
      multiple maternal-fetal interfaces may contribute to several pregnancy
      pathologies associated with placental dysfunction, including pre-eclampsia,
      intrauterine growth restriction, and preterm labor. We herein discuss mechanisms
      by which TLRs regulate the maternal immune response during normal and abnormal
      gestation, and we highlight recent data that assign a role to TLRs in the
      pathophysiology of selected pregnancy-associated complications.

PMID- 19866381
TI  - Editors' malpractice: forward submitted letters (to the concerned authors), then
      reject them.
AB  - It seems that editors still enjoy an almost absolute power in deciding "what gets
      published" and are barely accountable. The rejection of two "Letters to the
      Editor" submitted by myself to different journals leads me to expose here the
      editors' confidentiality breach inherent to improperly sharing unpublished
      manuscripts with the challenged authors. Although the scientific relevance of the
      issues raised here is virtually null, these experiences are consistent with the
      view that full peer review starts only after publication, highlight certain
      editorial malpractices, and stress that we all should promote scientific
      integrity.

PMID- 19866382
TI  - Self-regulated learning in younger and older adults: does aging affect
      metacognitive control?
AB  - Two experiments examined whether younger and older adults' self-regulated study
      (item selection and study time) conformed to the region of proximal learning
      (RPL) model when studying normatively easy, medium, and difficult vocabulary
      pairs. Experiment 2 manipulated the value of recalling different pairs and
      provided learning goals for words recalled and points earned. Younger and older
      adults in both experiments selected items for study in an easy-to-difficult
      order, indicating the RPL model applies to older adults' self-regulated study.
      Individuals allocated more time to difficult items, but prioritized easier items
      when given less time or point values favoring difficult items. Older adults
      studied more items for longer but realized lower recall than did younger adults.
      Older adults' lower memory self-efficacy and perceived control correlated with
      their greater item restudy and avoidance of difficult items with high point
      values. Results are discussed in terms of RPL and agenda-based regulation models.

PMID- 19866383
TI  - Hypnotic illusions and clinical delusions: hypnosis as a research method.
AB  - INTRODUCTION: Hypnosis is not only intrinsically interesting, but it can be used
      instrumentally as a powerful tool to investigate phenomena outside its immediate
      domain. In focusing on instrumental hypnosis research, we first sketch the many
      contributions of hypnosis across a range of areas in experimental
      psychopathology. In particular, we summarise the historical and more recent uses
      of hypnosis to create and explore clinically relevant, temporary delusions.
      METHODS: We then describe in detail the steps that hypnosis researchers take in
      constructing a hypnotic paradigm to map the features and processes shared by
      clinical and hypnotic delusions, as well as their impact on information
      processing (including autobiographical memory). We illustrate with hypnotic
      versions of mirrored-self misidentification, somatoparaphrenia, alien control,
      and identity delusions. RESULTS: Finding indicate that hypnotic analogues can
      produce compelling delusions with features that are strikingly similar to their
      clinical counterparts. These similarities encompass phenomenological features of
      delusions, delusional resistance to challenge, and autobiographical memory during
      delusions. CONCLUSIONS: We recognise important methodological issues and
      limitations of such hypnotic analogues, including: indexing response (behaviour
      vs. experience), alternative explanations (e.g., social compliance), the need for
      converging data, the need for close and continuing dialogue between the clinic
      and the laboratory, and generalisability of the findings.

PMID- 19866384
TI  - Reducing MRSA infections in college student athletes: implementation of a
      prevention program.
AB  - An interventional prevention program, Training CAMP Program, was implemented with
      college football players (n = 98) in a Midwestern NCAA Division II college during
      the 2008 college football season. The program goal was a 50% reduction in
      community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) cases,
      as compared to the previous 3 seasons' average number of cases (12.6). Results
      showed a greater than 75% reduction in CA-MRSA in the target population, with
      only 3 cases recorded for the entire 2008 college football season. A 1-group
      pretest-posttest design paired t-test revealed increased knowledge and knowledge
      retention. Program description, implementation, evaluation, cost-effectiveness,
      and future recommendations are described.

PMID- 19866385
TI  - Indicators of health-related quality of life in heart failure family caregivers.
AB  - Indicators of caregiver health-related quality of life (HRQL) were identified
      among 50 caregivers of older patients living with heart failure (HF). Using a
      cross-sectional design, caregivers were interviewed for perceptions pertaining to
      caregiver burden, depressive symptoms, patient disease severity, and HRQL.
      Caregiver burden explained 62% of the variance in caregiver HRQL, adjusted R(2) =
      .58, F (5, 44) = 14.54, p < .01. Caregiver depressive symptoms explained an
      additional 2% of variance in HRQL. Significant indicators of caregiver HRQL were
      in the burden domains of caregiver health and caregiver finances. The findings
      suggest the need for nurses to conduct caregiver health assessments to include
      screening for depression and assessment of the financial impact caregiving has on
      the caregiver. Interventions to improve caregiver health and lessen financial
      burdens should be investigated in future HRQL studies among HF caregivers.

PMID- 19866386
TI  - Home environmental health risks of people with developmental disabilities living
      in community-based residential settings: implications for community-health
      nurses.
AB  - Chronic, long-term exposure to indoor air pollutants is increasingly being
      recognized as a threat to health. Vulnerable populations, such as those with
      cognitive disabilities, the elderly, and children, are frequently at increased
      risk from these hazards. This study assessed home environmental health hazards,
      home characteristics, and household practices that create risk in a sample of
      community-based group homes. A survey and a home environmental assessment of each
      home were used to assess the presence of neurotoxicants, such as lead, mercury,
      and pesticides, in the home and use of protective measures such as carbon
      monoxide detectors and radon testing.

PMID- 19866387
TI  - Community health nursing and cooperative extension: a natural partnership.
AB  - Community health nursing and cooperative extension represent two influential and
      respected disciplines in rural and frontier communities. The history and
      philosophy of the two disciplines reveal commonalities related to community-based
      health promotion and dissemination of research. A review of the extension and
      health sciences literature revealed some evidence of collaboration between
      extension and health science professionals, however very little documentation
      specifically of nurses' involvement with extension professionals. An exemplar of
      a highly effective ongoing cooperation between rural public health nurses and
      extension educators in one Idaho county is provided. This local interdisciplinary
      effort has resulted in enhanced community health promotion services, positive
      interprofessional relationships, and maximization of scarce resources. Nursing
      extension collaboration presents creative opportunities for interdisciplinary
      practice, research, and educational innovations to enhance the health of rural
      and frontier communities.

PMID- 19866388
TI  - What's new in alternative therapies for asthmatic children?
AB  - Nurses require current information about popular complementary and alternative
      medicine for pediatric asthma. This integrative review searched scientific
      literature in PubMed and WEB of Science from 2004 to 2009 via key terms: asthma
      complementary medicine, nursing complementary pediatric asthma, asthma herbal,
      and herbal pediatric asthma. Nine journal articles met the inclusion criteria of
      containing data collection and analysis for biologically based therapies for
      pediatric asthma. Evidenced-based research on this focus topic is still in its
      initial stages. Two themes of maximizing the diet and augmenting conventional
      therapy with Traditional Chinese Medicine may serve as conduits of patient
      education.

PMID- 19866390
TI  - Alzheimer's disease neuropathologic changes in semantic dementia.
AB  - Neuropathologic change underlying primary progressive aphasia (PPA) most commonly
      includes one of the frontotemporal lobar degenerations, such as FTLD-tau or FTLD
      ubiquitin. The next most frequent etiology of PPA is Alzheimer's disease (AD). We
      describe 5 subjects with clinical diagnoses of semantic dementia, who underwent
      longitudinal clinical evaluation and postmortem neuropathology examination of the
      central nervous system. This case series examines retrospectively which clinical
      parameters might have pointed to the neuropathological diagnosis of AD.
      CONCLUSION: family history of late onset dementia, APOEepsilon4 status, combined
      features of semantic dementia and progressive non-fluent aphasia present early in
      illness, or generalized seizures, may indicate AD as the underlying pathology of
      semantic dementia.

PMID- 19866391
TI  - Impact of tremor severity on cognition in elderly patients with essential tremor.
AB  - Several clinical studies have demonstrated that patients with essential tremor
      (ET) may have cognitive deficits; however, detailed neuropsychological
      assessments in comparison with motor tasks in patients with ET have not been
      reported. We conducted a prospective study to determine the correlation of
      cognition with age, disease duration, and motor task severity in patients with
      ET. Forty-seven patients with ET who underwent clinical assessment using the Fahn
      Tolosa-Marin clinical rating scale and detailed neuropsychological investigation
      were included. Cognitive decline was significantly correlated with age at the
      time of examination, educational status, and tremor severity; cognitive decline
      however, was not related to disease duration or the presence of vascular risk
      factors. Multiple linear regression analysis revealed that the tremor severity
      was independently associated with cognitive impairment in patients with ET,
      regardless of age, gender, educational status, duration of ET symptoms, and
      vascular risk factors. Our results support the finding that the age at
      examination and educational status are risk factors associated with dementia in
      patients with ET, as with other types of dementia. In addition, the relationship
      between tremor severity and cognitive decline suggests there may be a
      pathophysiologic association between the two conditions, although the pathologic
      basis for dementia in the older onset ET cases requires further study.

PMID- 19866392
TI  - Duodenogastric reflux induced by endoscopic submucosal dissection.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) may cause
      excessive duodenogastric reflux (DGR) in a similar manner to distal gastrectomy,
      particularly after antral resections. We aimed to examine the occurrence of DGR
      after ESD. PATIENTS AND METHODS: Patients with gastric neoplasm for whom ESD was
      indicated were categorized according to lesion site: the antral group (lower [L]
      stomach, n = 46) and the nonantral group (upper or middle [U or M] stomach, n =
      49). Endoscopy was performed before ESD, the day after ESD, and 3 months after
      ESD, and the fasting bile acid concentration (BAC) in the gastric juice was
      analyzed. RESULTS: BAC values showed significant interaction between time point
      and group, although this association differed in the antral and nonantral groups.
      BACs on the day after ESD were higher in the antral group than in the nonantral
      group, but not the pre-ESD and 3 months post-ESD levels. In the antral group
      only, fasting BACs increased significantly the day after ESD and decreased to
      baseline levels 3 months post-ESD. There was also a correlation between BAC and
      lesion location in the antral subgroups, with significantly higher BACs found the
      day after ESD in patients with lesser curvature lesions. CONCLUSIONS: ESD of
      lesions in the antral lesser curvature may lead to a transient early increase in
      DGR. However, ESD does not result in long-term DGR, a factor that is known to
      increase the risk of carcinogenesis following gastrectomy.

PMID- 19866393
TI  - Colonoscopy perforation rate, mechanisms and outcome: from diagnostic to
      therapeutic colonoscopy.
AB  - BACKGROUND AND AIM: Perforation of the colon as a result of endoscopic
      manipulation is considered a severe adverse event. The goal of this review is to
      present the expected incidence of perforation in relation to varying levels of
      difficulty in endoscopic exploration and polypectomy together with the whole
      context of mechanisms, predisposing factors, diagnosis, and the strategic
      management plan. METHODS: An extensive search was undertaken in the Medline
      database for recent articles (published from 2000 onwards) in the English
      language using specific terms relating to the reported frequency of perforation
      during diagnostic and therapeutic colonoscopy in various medical settings and
      including morbidity, mortality, and appropriate management. Additional articles
      were retrieved irrespective of publication date to supplement where necessary
      data on important issues such as mechanisms of perforation, risk factors,
      diagnosis, and prevention. RESULTS: The frequency of perforation was found to be
      1 in 1400 for overall colonoscopies and 1 in 1000 for therapeutic colonoscopies.
      Varying perforation rates have been estimated for polypectomies, endoscopic
      mucosal resections, and endoscopic submucosal dissections. The mortality has
      dropped to 0 % in most studies, with the highest reported percentage being 0.02
      %. Advanced age, female sex, the presence of multiple co-morbidities,
      diverticulosis, and bowel obstruction have been shown to increase the risk of
      perforation. The decision between surgery and nonoperative treatment will depend
      on the type of injury, the quality of bowel preparation, the underlying colonic
      pathology, and the clinical stability of the patient. CONCLUSION: The perforation
      rate has declined in recent years in relation to more historical series, but
      there is now an increasing trend as a consequence of advanced interventional
      endoscopy. Awareness and experience are the only preventive measures that can
      limit the incidence of perforation.

PMID- 19866394
TI  - Staining for intracytoplasmic lumina and CAM5.2 increases the detection rate for
      bile duct cancers.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic biopsies have a low sensitivity for
      diagnosing malignant bile duct strictures. Tumor markers detected by mucin
      staining and immunohistochemistry may help to determine the malignancy of a
      biopsy specimen where histologic evaluation alone is nondiagnostic. PATIENTS AND
      METHODS: 61 patients who underwent forceps biopsies were retrospectively
      identified, yielding 49 and 40 biopsy specimens for strictures finally diagnosed
      as benign and malignant, respectively. Biopsy specimens were histologically
      evaluated and stained for p53, Ki-67, carcinoembryonic antigen (CEA), CA19-9,
      CAM5.2, and presence of intracytoplasmic lumina (ICL). Sensitivity, specificity,
      positive and negative predictive values (PPV and NPV), and positive and negative
      likelihood ratios (PLR and NLR) were calculated to evaluate the performance of
      each test. RESULTS: Histology alone provided sensitivity and specificity of 53 %
      and 100 %. Addition of ICL or CAM5.2 increased sensitivity to 73 % or 60 %,
      respectively, and provided excellent specificity, PPV, and PLR (ICL, 98 %, 97 %,
      and 36; CAM5.2, 100 %, 100 %, and infinite). Both stains in combination increased
      the sensitivity to 75 %. Staining for Ki-67, p53, CEA, and CA19-9 increased the
      sensitivity to detect malignancy (range 60 % to 83 %), but significantly reduced
      the specificity, PPV and PLR (ranges 73 % to 90 %, 72 % to 86 %, and 3 to 7,
      respectively). Markers in all combinations performed poorly as a negative test
      (NPV 69 % to 87 %, and NLR 0.19 to 0.55). CONCLUSIONS: Staining for tumor markers
      ICL and CAM5.2 can improve the diagnostic value of endoscopic biopsies, and may
      change the course of management for patients with indeterminate histological
      findings.

PMID- 19866395
TI  - Adhesion formation after peritoneoscopy with liver biopsy in a survival porcine
      model: comparison of laparotomy, laparoscopy, and transgastric natural orifice
      transluminal endoscopic surgery (NOTES).
AB  - BACKGROUND AND STUDY AIMS: Minimizing the invasiveness of operations by using
      natural orifice transluminal endoscopic surgery (NOTES) may reduce adhesion
      formation. The aim of the study was to compare rates of adhesion formation after
      peritoneoscopy with liver biopsy by laparotomy, laparoscopy, and transgastric
      NOTES. MATERIALS AND METHODS: Experimental comparative survival study, at a
      university hospital. using 18 female pigs weighing 35 - 40 kg. Peritoneoscopy
      with liver biopsy was randomized to one of three groups: laparotomy, laparoscopy,
      and transgastric NOTES. Preoperative, operative, and postoperative care was
      standardized. Main outcome measures were: (i) survival and complication rates;
      (ii) assessment of adhesion formation using the Hopkins Adhesion Formation Score
      at necropsy (day 14). RESULTS: 100 % of pigs with laparotomy and 33.3 % with
      laparoscopy had adhesions compared with 16.7 % who underwent transgastric NOTES.
      Documented adhesion bands totals for each group were: transgastric NOTES 1;
      laparoscopy 4; laparotomy 17. Median adhesion formation scores were: laparotomy
      2.5 (range 2 - 4), compared with laparoscopy 0.0 (0 - 2), and transgastric NOTES
      0.0 (0 - 1) ( P < 0.001). Spearman coefficient analysis revealed that correlation
      between adhesion scores assigned by two investigators was excellent (r = 0.99, P
      < 0.001, 95 % confidence interval [CI] 0.9978 - 0.9996). CONCLUSIONS: Although
      this was a short-term study, with a low number of animals, it showed that
      transgastric NOTES and laparoscopy are associated with statistically
      significantly lower rates of adhesion formation than open surgery when
      peritoneoscopy with liver biopsy is performed. Incidence and severity of
      adhesions were lowest with transgastric NOTES.

PMID- 19866396
TI  - An evidence-based consensus statement on the role and application of
      endosonography in clinical practice.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) has evolved over the past 20 years
      with the emergence of novel diagnostic and therapeutic indications. Our goal was
      to identify the best evidence supporting the use of EUS. MATERIALS AND METHODS: A
      six-step approach was employed to develop recommendations using accepted
      methodology. Twenty-two experienced endosonographers identified topics and
      reviewed studies using MeSH (medical subject headings) terminology and free text
      in PubMed. Medline and society abstracts were reviewed if necessary. The quality
      of evidence, the strength of recommendations, and level of consensus were graded
      and voted on. RESULTS: Consensus was reached for several clinical scenarios for
      which the impact of EUS findings was supported by a high level of evidence. These
      included diagnosis and staging of esophageal cancer, differential diagnosis of
      subepithelial lesions, thickened gastric folds, assessment of peritoneal
      involvement in patients with gastric cancer, mucosa-associated lymphoid tissue
      lymphoma, diagnosis of common bile duct/gallbladder stones, diagnosis of chronic
      pancreatitis, differential diagnosis of a solid mass in patients with chronic
      pancreatitis, differential diagnosis of pancreatic cyst, rectal cancer staging,
      and diagnosis and staging of non-small-cell lung cancer. The recommendations were
      adopted by the Brazilian Society of Gastrointestinal Endoscopy. Several
      indications continue to emerge and require additional validation.

PMID- 19866397
TI  - How to justify endoscopic submucosal dissection in the Western world.

PMID- 19866398
TI  - Diagnosing and staging bile duct cancer: cholangiographically guided biopsies or
      cholangioscopy?

PMID- 19866399
TI  - Endoscopic stone removal using a scissors papillotome followed by papillary
      balloon dilation in patients with Billroth II gastrectomy - a case series.

PMID- 19866401
TI  - Pancreatic stent insertion should not be a routine procedure after precutting in
      patients in whom access has failed with both ducts.

PMID- 19866403
TI  - The use of sildenafil in persistent pulmonary hypertension of the newborn.
AB  - We evaluated the effectiveness of sildenafil in the treatment of neonatal
      pulmonary hypertension. We performed a double-blind randomized clinical trial in
      51 full-term infants with persistent pulmonary hypertension confirmed by Doppler
      echocardiography. Patients were divided in two groups: 20 infants in group A
      received placebo when the oxygenation index was >20, and 31 infants in group B
      received 3 mg/kg of oral sildenafil every 6 hours. Arterial blood gases were
      taken at 1, 4, 7, 13, 19, and 25 hours after treatment was started. Main outcome
      measures were oxygenation changes, time on mechanical ventilation, and mortality.
      Both groups were comparable in general variables as well as in illness severity.
      We observed better oxygenation parameters after 7 hours of sildenafil treatment,
      but no significant changes were found in the placebo group. Mortality was higher
      in the placebo group (40%) than in those infants who received sildenafil (6%; P =
      0.004), although no difference was found in time on mechanical ventilation
      between groups. Our results confirm that sildenafil may be a useful adjuvant
      therapy for term infants with pulmonary hypertension in centers lacking inhaled
      nitric oxide and extracorporeal membrane oxygenation.

PMID- 19866404
TI  - Outcomes in neonates with gastroschisis in U.S. children's hospitals.
AB  - Our objectives are to report patient characteristics, comorbidities, and outcomes
      for gastroschisis patients and analyze factors associated with mortality and
      sepsis. Using Pediatric Health Information System data, we examined neonates with
      both an International Classification of Diseases, 9th Revision diagnosis (756.79)
      and procedure (54.71) code for gastroschisis (2003 to 2008). We examined
      descriptive characteristics and conducted multivariate regression models
      examining risk factors for mortality, during the birth hospitalization, and
      sepsis. Analysis of 2490 neonates with gastroschisis found 90 deaths (3.6%) and
      sepsis in 766 (31%). Critical comorbidities and procedures are cardiovascular
      defects (15%), pulmonary conditions (5%), intestinal atresia (11%), intestinal
      resection (12.5%), and ostomy formation (8.3%). Factors associated with mortality
      were large bowel resection (odds ratio [OR] 8.26, 95% confidence interval [CI]
      1.17 to 58.17), congenital circulatory (OR 5.62, 95% CI 2.11 to 14.91), and
      pulmonary (OR 8.22, 95% CI 2.75 to 24.58) disease, and sepsis (OR 3.87, 95% CI
      1.51 to 9.91). Factors associated with sepsis include intestinal ostomy (OR 2.94,
      95% CI 1.71 to 5.05), respiratory failure (OR 2.48, 95% CI 1.85 to 3.34),
      congenital circulatory anomalies (OR 1.58, 95% CI 1.10 to 2.28), and necrotizing
      enterocolitis (OR 4.38, 95% CI 2.51 to 7.67). Further investigation into
      modifiable factors such as small bowel ostomy and prevention of sepsis and
      necrotizing enterocolitis is warranted to guide surgical decision making and
      postoperative management.

PMID- 19866405
TI  - Perinatal neurofibromatosis: two case reports and review of the literature.
AB  - Neurofibromatosis-1 (NF-1) is an autosomal-dominant genetic disorder with many
      different manifestations. Some may have evidence of the disease at birth. A 66
      year (1942 to 2008) retrospective review of 36 patients including 7 fetuses and
      29 neonates with NF-1 was performed. Only patients with NF-1 lesions detected
      before birth by imaging or noted in the first month of life were entered into the
      review. There was a strongly positive family history of the disease of 70%. The
      most common presenting findings in the fetus were hydrops, macrocephaly, and
      thickened neck soft tissues and those in the neonate were cafe au lait macules,
      skin nodules, and buphthalmos. Survivors developed serious sequelae (e.g.,
      progressive growth of neurofibromas within the neck and mediastinum leading to
      increasing airway obstruction and death; an enlarging, proptotic, and
      glaucomatous eye; and occurrence of brain and malignant nerve sheath tumors).
      Congenital generalized (disseminated) neurofibromatosis was associated with a
      poor prognosis, with a mortality rate of 92%. Survival rates for patients
      detected before and after birth were 28% and 62%, respectively. The overall
      survival was 20/36 or 56%.

PMID- 19866406
TI  - [Smoking behaviour after laryngectomy].
AB  - BACKGROUND: Tobacco smoking is an important risk factor for laryngeal cancer. Aim
      of this study was to investigate the prevalence of smoking and to identify
      factors that can promote tobacco abstinence. PATIENTS AND METHODS: In a multi
      centre cross-sectional study, 187 patients after laryngectomy were surveyed
      regarding their smoking behaviour. Instruments used were the questionnaire
      "Quality of Life after Laryngectomy" (Ackerstaff & Hilgers) and the
      "Questionnaire of Health Behaviour" ("Fragebogen zur Erfassung des
      Gesundheitsverhaltens", Dlugosch & Krieger). RESULTS: Life time prevalence of
      tobacco smoking was 89%, whereas current prevalence was only 6%. None of the
      laryngectomies believed tobacco consumption to be safe. 24% thought that their
      tumour was caused mainly by smoking, although the current prevalence of smoking
      was not related to that number. 74% of all ex-smokers had stopped smoking at the
      time of the laryngectomy. CONCLUSIONS: Only a small fraction of laryngectomized
      patients do smoke several years after the operation. Anti-tobacco interventions
      should therefore be focused on high risk persons, not on the entire patient
      population.

PMID- 19866407
TI  - [Progressive expansion of the left forehead. Pneumocele of the left frontal
      sinus].

PMID- 19866408
TI  - [Unilateral recurrent tumor of the nasal cavity and the paranasal sinuses].

PMID- 19866409
TI  - Improved outcomes in paediatric intestinal failure with aggressive prevention of
      liver disease.
AB  - BACKGROUND/PURPOSE: A protocol-driven care algorithm for the care of intestinal
      failure (IF) centred on therapies to prevent Parenteral Nutrition Associated
      Cholestasis (PNAC) was instituted in 2006. We report our results from 2006-2009,
      and compare them to the outcomes of our previous cohort of patients (1998-2006).
      METHODS: With regional ethics board approval, we have been prospectively
      gathering data on patient with IF cared for by our regional surgical unit. IF was
      defined as a residual bowel length of <40 cm or a requirement for PN for greater
      than 60 days. With the development of a multidisciplinary care team, a protocol
      driven strategy to prevent PNAC was instituted in 2006, with aggressive
      introduction of enteral feeds, use of prophylactic antibiotics to prevent
      bacterial overgrowth, lipid reduction and use of a fish oil-derived lipid
      preparation for cholestasis and Serial Transverse Enteroplasty (STEP) if bowel
      dilation occurred. RESULTS: In the era from 1998-2006, 33 patients were
      identified, with a 72% survival; the direct bilirubin averaged 112+/-34 microM/L
      after 3 months of PN. 8/33 (27%) of patients received prophylactic antibiotics,
      and none received fish oil-based lipids. The most common causes of IF were
      gastroschisis (30%) and atresia (21%); 31 of 33 patients were infants. Average
      time to intestinal rehabilitation/death was 4.5+/-3 months. All deaths were
      related to sepsis or PN/liver failure. In the era from 2006-2009, 22 patients
      have been followed, with 100% survival*. Average bilirubin after 3 months of PN
      was 8+/-2.2 microM/L*, 20/22 (90%)* received prophylactic antibiotics, and
      6/22(27%)* received fish oil-based lipid PN. The common causes of IF were
      gastroschisis 15/22 (68%) and atresia (27%). 18/22 are weaned from PN, and the
      average time to intestinal rehabilitation was 2.7+/-1.3 months, 4 patients
      underwent STEP procedures. (*p<0.05 by Fischer's exact or Student's t-test, data
      mean+/-SD). CONCLUSIONS: The institution of an aggressive protocol of advancing
      enteric feeds, oral antibiotic prophylaxis for bacterial overgrowth, fish oil
      based lipid use, and the STEP procedure for dilated bowel has resulted in an
      apparent increase in survival and a remarkable improvement in liver function in a
      paediatric IF population. Further studies to define the relative importance of
      these therapies are recommended.

PMID- 19866410
TI  - Evaluation of a possible inflammatory response after appendectomy for non
      perforated appendicitis in children.
AB  - BACKGROUND: The inflammatory process in the post-appendectomy period is not well
      characterized. In a pilot study, we prospectively followed the kinetics of
      different inflammatory mediators before and after appendectomy in children, and
      compared the results of the groups open appendectomy (OA) and laparoscopic
      appendectomy (LA). MATERIAL AND METHODS: Levels of sP-selectin, tPA, MCP-1, IL-6,
      IL-8, sVCAM-1, and sCD40L were measured before appendectomy and on the next three
      consecutive days in the serum of 25 children (16 males and 9 females) aged 7 - 16
      years (mean 12.6+/-2.47 years) with non-perforated acute appendicitis. RESULTS:
      LA and OA were performed in 16 and 9 patients respectively. None of the markers
      of inflammation differed significantly by surgical approach at any point of
      observation. However, sP-selectin, MCP-1 and sVCAM-1 levels were found to have
      significantly different postoperative kinetics with a trend towards higher values
      in the laparoscopic group compared to the open appendectomy group (p=0.034,
      p=0.016 and p=0.025, respectively). CONCLUSIONS: The cytokines sP-selectin, MCP-1
      and sVCAM-1 may play a role in the possible post-appendectomy cytokine activation
      after non-perforated appendicitis. Since this phenomenon is more evident after LA
      than after OA, the contribution of the different LA procedures has to be further
      investigated.

PMID- 19866412
TI  - Immediate hip spica for unstable femoral shaft fractures in preschool children:
      still an efficient and effective option.
AB  - INTRODUCTION: Despite the increasing use of flexible intramedullary nailing for
      the treatment of femoral shaft fractures during growth, the use of acute or
      delayed plaster fixation is still a widely practised alternative in preschool
      children. The purpose of this retrospective study was to analyse outcome
      following acute casting in preschool children with a focus on acceptable initial
      leg length discrepancy and angulation. MATERIAL AND METHODS: A retrospective
      study was performed of 46 children with femoral shaft fractures treated
      conservatively. It was possible to verify the outcome in 22 children with an
      average follow-up time of 7.5 years. We compared initial shortening and mal
      angulation to radiographic data at the time of consolidation and clinical
      outcome. RESULTS: Most children sustained their fracture by falling out of bed or
      from their parent's arm. A hip spica including the foot of the injured side, a
      pelvic ring and the thigh of the uninjured leg was applied under sedation and
      manual traction. Mean time of hospital stay was 1.4 days (range, 2 h-20 days).
      The average immobilisation time was 16.7 days (range, 0-30 days). At follow-up,
      on average 7.5 years after trauma, only one patient showed a leg length
      discrepancy greater than 2 cm. One patient showed a minor valgus and rotational
      deformity. CONCLUSION: The long-term outcome for conservatively treated femoral
      shaft fractures in preschool children is very good, even in severely dislocated
      fractures. Our data show that even initial shortening of up to 2.5 cm can be
      treated successfully with a spica cast.

PMID- 19866411
TI  - The influence of enzymes on adhesive processes in the abdominal cavity.
AB  - INTRODUCTION: Intraperitoneal adhesions remain a common problem after abdominal
      surgery. However, the advent of targeted, specific agents as a directed therapy
      against inflammatory and neoangiogenesis raises the prospect of a new approach
      for anti-adhesion strategies. METHODS: 70 adult rats were divided into two
      groups: an enzyme group (35 rats) and a control group (35 rats). Following
      laparotomy the visceral peritoneum of the cecum and inner layer the abdominal
      cavity were abraded. In the enzyme group the preparation Wobenzym (a combination
      of animal and vegetable proteases plus rutoside) dissolved in 2 ml of sterile
      0.9% NaCl was administered to the rats through a gastric probe over a period of
      21 days. The control animals received the same quantity of saline without the
      preparation. On the 1st, 3rd, 7th and 21st postoperative days 8 animals from each
      group were sacrificed. VEGF, bFGF and laminin were detected in the visceral and
      parietal peritoneum by immunohistochemistry. RESULTS: The mean adhesion grades of
      the enzyme group were significantly lower than in the control group. A comparison
      of the two groups showed that the expression of VEGF, bFGF and laminin in the
      enzyme group was lower than in the control group. Moreover, in the enzyme group
      the concentration of bFGF and laminin peaked on the 7th day, while in the control
      group the maximum concentrations peaked on day 21. CONCLUSIONS: Our study found
      that oral poly-enzyme therapy following laparotomy and abrasion of the visceral
      and parietal peritoneum reduces the extent of postoperative intestinal adhesions.
      This favorable effect can be explained by the lower levels of angiogenic agents
      (VEGF, bFGF) and laminin after the administration of hydrolytic enzymes.

PMID- 19866413
TI  - Kidney transplantation in children with bladder augmentation or ileal conduit
      diversion.
AB  - INTRODUCTION: Various congenital and acquired diseases of the lower urinary tract
      can lead to chronic renal failure requiring renal replacement therapy. AIM: The
      aim of the study was to assess problems and results of kidney transplantation in
      children with significant lower urinary tract dysfunction. MATERIALS AND METHODS:
      Between 1984 and 2007, there were 33 kidney transplantations in children with end
      stage renal disease and severe lower tract dysfunction out of 539 kidney
      transplantations performed in our department. The patients were 23 males and 10
      females. Thirty patients received a kidney from a deceased donor, the remaining 3
      from a living related donor. The age at transplantation ranged from 2.25 years to
      19 years. In 26 patients an ileal conduit modo Bricker was created (in 21
      patients at transplant operation). Bladder augmentation was performed in 6
      patients and a continent urinary reservoir was created in 1. RESULTS: Post
      transplant follow-up ranged from 7 to 88 months (mean 32 months). Overall patient
      survival is 100% and graft survival is 97%. Creatinine concentrations ranged from
      0.3 to 3.4 mg% (mean 0.92 mg%). Surgical complications were diagnosed in 16
      patients. All surgical complications were treated successfully and none of them
      caused graft loss. Urinary tract infections (UTI) were the most commonly observed
      complication, occurring in 26/33 (78%) patients, but the majority of these UTI
      were asymptomatic and had no influence on graft function. CONCLUSIONS: Kidney
      transplantation in children with lower urinary tract dysfunction and end-stage
      renal failure offers excellent medium term results in our experience, despite the
      creation of non-standard urinary drainage. Recurrent urinary tract infections are
      the most common complications in these patients, but in the majority of cases
      this does not lead to impairment of graft function.

PMID- 19866414
TI  - A novel technique of sutureless colorectal anastomosis by bipolar coagulation.
AB  - AIM: Aim of the study was to test the safety and efficacy of sutureless
      colorectal anastomosis using bipolar coagulation. MATERIAL AND METHODS: Thirty
      six Wistar albino rats were used. The rectum just proximal to the peritoneal
      reflection was transected in 22 rats (Group 1), and the bowel ends were
      anastomosed or welded end-to-end using bipolar coagulating forceps (Scoville
      Greenwood, 60-1765-001, ConMed, USA). Coagulation using 60 milliamperes took one
      second for each weld. In 14 rats (Group 2), bowel anastomosis was carried out by
      hand-sewn sutures. The animals were followed up for general condition and body
      weight, and were sacrificed at six weeks. The anastomoses were studied with
      regard to burst pressure, stenosis and histopathology. RESULTS: All rats
      survived, and body weight gain was significant (p<0.01 for Group 1, p<0.05 for
      Group 2). There were no intraabdominal complications (leakage, obstruction,
      etc.), except in one rat (in Group 2), who had intraabdominal abscess. Although
      intraluminal pressure was increased to 40 cm H2O with extensive stretching of the
      colorectal segment, the anastomoses did not burst or open in either the
      sutureless or sutured groups. The bowel diameter 1 cm distal and 1 cm proximal to
      the anastomoses did not show any difference between both groups. Neomucosa
      completely covered 78% of sutured anastomoses and 36% of sutureless anastomoses
      (p<0.05). Inflammation developed in 78% of sutured anastomoses and 36% of
      sutureless anastomoses (p<0.05). Edema, giant cell and mast cell infiltration
      were equivalent in both anastomoses. Lymphoid tissue hyperplasia markedly
      appeared in the sutureless anastomoses (p<0.01). CONCLUSION: This simple
      technique of sutureless colorectal anastomosis may be useful and offer an
      alternative to other colorectal anastomosis techniques.

PMID- 19866415
TI  - Do we need laparoscopic abdominal exploration for a testicular nubbin palpated in
      the inguinal region? A case with type IV polyorchidism.

PMID- 19866416
TI  - Pulmonary hypertensive crisis requiring ECMO associated with re-warming from
      whole body hypothermia for hypoxic ischemic encephalopathy: clinical observations
      from a case series.

PMID- 19866417
TI  - Lipoblastoma in the masticator space of an infant.

PMID- 19866418
TI  - Spontaneous fistulization of a liver abscess into the stomach.

PMID- 19866419
TI  - Colonoscopy-related esophageal perforation: report of two cases.

PMID- 19866420
TI  - Delayed life-threatening splenic rupture after endoscopic ultrasound evaluation
      of a pancreatic tumor.

PMID- 19866421
TI  - Polypectomy of a colonic muco-submucosal elongated polyp.

PMID- 19866422
TI  - Gastric adenocarcinoma with a submucosal cyst treated by endoscopic submucosal
      dissection (ESD).

PMID- 19866423
TI  - The presence of percutaneous endoscopic gastrostomy (PEG)-related postprocedural
      pneumoperitoneum.

PMID- 19866424
TI  - Intestinal strongyloidiasis as a presenting symptom of HTLV-1-associated adult T
      cell leukemia/lymphoma.

PMID- 19866425
TI  - Usefulness of an ultrathin endoscope in recanalization of a disrupted fistulous
      tract following percutaneous endoscopic gastrostomy or jejunostomy.

PMID- 19866426
TI  - Novel endoscopic findings in gastric giardiasis.

PMID- 19866428
TI  - Ampullary metastasis from breast cancer: an unusual finding.

PMID- 19866427
TI  - Colonic metastasis from carcinoma of the breast presenting with colonic erosion.

PMID- 19866429
TI  - A new capsule endoscopy feature of serosal eosinophilic enteritis.

PMID- 19866431
TI  - Novel diagnostic methods for early-stage squamous cell carcinoma of the anal
      canal successfully resected by endoscopic submucosal dissection.

PMID- 19866430
TI  - Lansoprazole-associated collagenous colitis: unique presentation, similar to
      ischemic colitis.

PMID- 19866432
TI  - Oropharyngeal dysphagia and language delay in partial trisomy 9p: case report.
AB  - The phenotype of partial trisomy 9p includes global developmental delay,
      microcephaly, bulbous nose, downturned oral commissures, malformed ears,
      hypotonia, and severe cognitive and language disorders. We present a case report
      and a comparative review of clinical findings on this condition, focusing on
      speech-language development, cognitive abilities and swallowing evaluation. We
      suggest that oropharyngeal dysphagia should be further investigated, considering
      that pulmonary and nutritional disorders affect the survival and quality of life
      of the patient. As far as we know, this is the first study of a patient with
      partial trisomy 9p described with oropharyngeal dysphagia.

PMID- 19866433
TI  - Internal phloem in an interspecific hybrid of cassava, an indicator of breeding
      value for drought resistance.
AB  - We examined the stem anatomy of Manihot esculenta Crantz and its hybrid with M.
      oligantha Pax. Cross-sections were stained with safranin-alcian blue. Manihot
      esculenta and its hybrid were found to have the same vascular structure in
      bicollateral bundles with internal phloem, which has been associated with drought
      resistance in other plant groups. If this association is established for cassava,
      it would facilitate the selection of lines that are more adapted to arid regions.
      This is the first report of internal phloem in this genus.

PMID- 19866434
TI  - Analysis of protein expression and a new prokaryotic expression system for goat
      (Capra hircus) spermadhesin Bdh-2 cDNA.
AB  - Low purification efficiency and incomplete characterization of male goat (buck)
      spermadhesins (Bdhs) prompted us to develop an effective system to produce
      recombinant Bdhs (rBdhs). Bdh-2 cDNA was inserted into a prokaryotic expression
      plasmid, pTrcHis TOPO. The pTrcHis-Bdh-2 system was constructed to produce a
      His(6) fusion protein in Escherichia coli Top10 cells. Recombinant clones were
      selected by growth in ampicillin-enriched medium, PCR amplification and
      nucleotide sequencing. The inserted cDNA was completely identified and
      recombinant protein synthesis was monitored by SDS-PAGE, followed by
      immunoblotting with monoclonal anti-His antibody. Expression of insoluble rBdh-2
      was achieved at 0.1 to 2.0 mM IPTG, after 2 to 6 h of induction. Significantly
      increased production of rBdh-2 (P < 0.01) occurred with 1.5 mM IPTG after 2 h of
      induction, and with 0.3 mM IPTG after 4 h in culture. Among the induction times
      investigated, a period of 6 h gave the lowest levels of rBdh-2 production; with a
      6-h incubation, there were no significant differences in rBdh-2 production for
      the various concentrations of IPTG tested (P > 0.05). The apparent molecular
      weight of rBdh-2 was 15.85 +/- 0.09 kDa, calculated by image analysis of
      membranes. This is similar to the theoretical molecular weight of 15.5 kDa
      predicted from the nucleotide sequence. Prior to this study, expression of
      recombinant goat spermadhesin had never been reported. Thus, an effective
      prokaryotic rBdh-2 expression system was developed in order to provide an
      adequate tool for studying biofunctions of goat spermadhesins.

PMID- 19866435
TI  - POPREP: a generic report for population management.
AB  - Genetic variation provides a basis upon which populations can be genetically
      improved. Management of animal genetic resources in order to minimize loss of
      genetic diversity both within and across breeds has recently received attention
      at different levels, e.g., breed, national and international levels. A major need
      for sustainable improvement and conservation programs is accurate estimates of
      population parameters, such as rate of inbreeding and effective population size.
      A software system (POPREP) is presented that automatically generates a typeset
      report. Key parameters for population management, such as age structure,
      generation interval, variance in family size, rate of inbreeding, and effective
      population size form the core part of this report. The report includes a default
      text that describes definition, computation and meaning of the various
      parameters. The report is summarized in two pdf files, named Population Structure
      and Pedigree Analysis Reports. In addition, results (e.g., individual inbreeding
      coefficients, rate of inbreeding and effective population size) are stored in
      comma-separate-values files that are available for further processing. Pedigree
      data from eight livestock breeds from different species and countries were used
      to describe the potential of POPREP and to highlight areas for further research.

PMID- 19866436
TI  - Genetic variability and heterogeneity of Venezuelan equine encephalitis virus
      vector Ochlerotatus taeniorhynchus (Diptera: Culicidae) populations of the
      Colombian Atlantic coast, based on microsatellite loci.
AB  - In Colombia, the mosquito Ochlerotatus taeniorhynchus has been identified as an
      efficient vector of the epidemic-epizootic Venezuelan equine encephalitis virus.
      We evaluated the genetic variability and heterogeneity of this mosquito in
      Colombian populations using eight microsatellite DNA loci. Two hundred and ten
      mosquito specimens collected from seven populations of the Colombian Atlantic
      coast (San Bernardo del Viento, Covenas, Cartagena, Barranquilla, Cienaga,
      Dibulla, and Riohacha) were analyzed. We found five polymorphic microsatellite
      loci, with 19 alleles giving 62.5% polymorphism; the mean number of alleles per
      locus was 3.8. The mean expected heterogeneity ranged from 0.568 to 0.660. Most
      of the polymorphic microsatellite loci were in Hardy-Weinberg disequilibrium, due
      to both deficit and excess of heterozygotes. The Fst statistic gave a total value
      of 0.0369, reflecting low genetic differentiation among the populations and, as a
      consequence, a low degree of structuring among them, while gene flow was high (Nm
      = 6.52); these findings point to genetic homogeneity among these populations.
      There was no significant linkage disequilibrium between genotype pairs of the
      various populations. We concluded that this mosquito is distributed in local
      populations along the Colombian Atlantic coast; these findings will be useful for
      developing strategies for controlling this vector.

PMID- 19866437
TI  - Structure characterization of human cytomegalovirus UL131A, UL130 and UL128 genes
      in clinical strains in China.
AB  - Human cytomegalovirus (HCMV) genetic determinants of endothelial cell tropism,
      leukocytes and dendritic cells have been identified in the genes UL131A, UL130,
      and UL128. We examined the structure of these three genes in HCMV. Eighteen low
      passage clinical isolates and five non-passage strains from congenitally HCMV
      infected infants in China were used to assess the structures of the UL131A,
      UL130, and UL128 genes and to find possible relationships between sequence
      polymorphism and different signs of HCMV disease. Comparisons were made between
      the UL131A, UL130, and UL128 genes of clinical strains and published sequences of
      Towne and Merlin strains. The UL131A coding region in the clinical strains was
      similar to that of Towne and Merlin strains, while UL130, and UL128 coding
      regions in the clinical strains were parallel with those of Towne and Merlin,
      respectively. Sequence comparison indicated that the UL130, and UL128 genes
      encode chemokine-like proteins in the clinical strain; the transmembrane regions
      of UL131A, and UL130 were conserved in all clinical and reference strains. The
      three genes of clinical strains from infants with different signs of HCMV disease
      had similar structure characterization. We conclude that the UL131A, UL130, and
      UL128 genes are highly conserved in these clinical strains. No correlation was
      found between the structure of the three genes and variations in HCMV disease.
      The finding of chemokine-like domains in UL130, and UL128 putative proteins
      suggests that the predicted products play a role in HCMV infectivity.

PMID- 19866439
TI  - Cytogenetic findings in an epithelioid sarcoma with angiomatoid features. A case
      report.
AB  - Epithelioid sarcoma is a rare, aggressive soft tissue tumor of unknown
      histogenesis showing predominantly epithelioid cytomorphology. We conducted a
      conventional and molecular cytogenetic study of a 27-year-old male with
      epithelioid sarcoma with angiomatoid features. Cytogenetic analysis of
      epithelioid sarcoma metaphase spreads by GTG-banding revealed a diploid
      chromosome complement with structural and numerical aberrations. Comparative
      genomic hybridization analysis demonstrated the amplification of 3p24-pter,
      4p15.2-p16 and 18q23, while chromosome losses involved 3p13-p14, 3q24-q26.1,
      9q21, and 11q21. Fluorescence in situ hybridization assessment showed normal
      hybridization patterns for the C-MYC and CCND1 loci; CCND1 RNA overexpression was
      detected by real-time polymerase chain reaction analysis. Genetic evaluation of
      this rare condition may be useful in determining if epithelioid sarcoma is
      associated with a distinct genetic background.

PMID- 19866438
TI  - Correlation of aberrant expression of p53, Rad50, and cyclin-E proteins with
      microsatellite instability in gallbladder adenocarcinomas.
AB  - Gallbladder carcinoma is an uncommon, but highly malignant tumor, with poor
      prognostic, and diagnostic manifestations in early stages. The Indian Council of
      Medical Research reported increased incidence of gallbladder carcinoma in the
      surviving population of the Bhopal gas tragedy that involved exposure of more
      than 500,000 people to methyl isocyanate gas. The severity of exposure, and
      increased multi-systemic morbidity in the survivors stimulated us to examine the
      molecular changes leading to gallbladder carcinoma. Surgically resected samples
      (N = 40) of gallbladder carcinoma were studied for the p53, Rad50, and cyclin-E
      expression by immunohistofluorescence bioimaging. Among the 40 samples, 23, 11,
      and 10 showed p53, Rad50, and cyclin-E expression, respectively, in moderately
      differentiated adenocarcinomas, demonstrating the prevalence and invasiveness of
      this disease in the methyl isocyanate-exposed population (P = 0.0009).
      Nevertheless, co-expression of Rad50, and cyclin-E with p53 was absent in
      adenomas with dysplasia, demonstrating their independent roles. We conclude that
      there was altered expression of p53, Rad50, and cyclin-E in the malignant
      transformation of gallbladder carcinoma in this methyl isocyanate gas-exposed
      cohort. Hence, these proteins may be useful as markers to identify premalignant
      lesions that are likely to progress into malignant adenocarcinoma.

PMID- 19866440
TI  - The epiphyseal plate: nutritional and hormonal influences; hereditary and other
      disorders.
AB  - This article reviews nutritional and hormonal influences, diseases with uncertain
      etiology, and hereditary disorders affecting the growth and development of the
      long bones in dogs and cats.

PMID- 19866441
TI  - The epiphyseal plate: physiology, anatomy, and trauma.
AB  - This article reviews the development of long bones, the microanatomy and
      physiology of the growth plate, the closure times and contribution of different
      growth plates to overall growth, and the effect of, and prognosis for, traumatic
      injuries to the growth plate. Details on surgical treatment of growth plate
      fractures are beyond the scope of this article.

PMID- 19866442
TI  - Applied dermatology: diagnosing the cause of feline pruritus.
AB  - Pruritus is a common clinical sign of many dermatologic disorders in cats. This
      article presents a brief overview of clues in the history, presentation, and
      results of diagnostic tests that can help in diagnosing the underlying cause.

PMID- 19866443
TI  - Surgical views: Surgical treatment of urethral sphincter mechanism incompetence
      in dogs.
AB  - Urinary incontinence--loss of voluntary control over the retention and expulsion
      of urine--is a common medical problem in small animal patients. Incontinence
      occur when pressure within the bladder exceeds urethral pressure. Incontinence
      may result from a variety of etiologies, including congenital anatomic
      abnormalities of the lower urinary and reproductive systems (ureter, bladder,
      bladder neck, urethra, vagina,vestibule) as well as neurologic, neoplastic,
      infectious, and inflammatory disease.

PMID- 19866444
TI  - Tritrichomonas foetus: a new agent of feline diarrhea.
AB  - Tritrichomonas foetus is a single-celled, flagellated protozoal parasite that
      colonizes the feline colon and distal ileum. Infected cats may be asymptomatic or
      may have clinical signs that include malodorous large bowel diarrhea. T. foetus
      infection is common in, but not limited to, high-density populations of young,
      purebred cats. Testing for this parasite is still not routine at most veterinary
      clinics, and T. foetus is often misdiagnosed as Giardia spp. T. foetus-specific
      tests (fecal culture and polymerase chain reaction) should be considered in cats
      with large bowel diarrhea, especially those in which traditional diagnostics and
      treatments for other causes of feline large bowel diarrhea have failed to reach a
      clinical resolution. Recognition of this newly emerging disease and appropriate
      sample handling are critical for the detection and treatment of feline
      trichomoniasis.

PMID- 19866445
TI  - Canine primary hyperparathyroidism.
AB  - Primary hyperparathyroidism is a common cause of hypercalcemia in dogs. The
      diagnosis requires careful interpretation of test results, and treatment involves
      removal of the affected gland(s).

PMID- 19866446
TI  - Diffusion-weighted MRI in lungs of normal fetuses and those with congenital
      diaphragmatic hernia.
AB  - OBJECTIVE: To prospectively determine apparent diffusion coefficient (ADC) values
      of normally developing fetal lungs over gestation, as obtained by diffusion
      weighted (DW) magnetic resonance imaging (MRI) and to investigate its potential
      application in fetuses with congenital diaphragmatic hernia (CDH). METHODS:
      Informed consent was obtained for this cross-sectional study of 93 fetuses with
      normal lungs and 14 with isolated left-sided CDH, assessed between 18 and 40
      weeks of gestation. MRI delineation of left and right lungs was performed on the
      native DW image, b0, and three values of ADC, corresponding to the overall value
      (ADC(avg)), and values for low and high values of b (ADC(low) and ADC(high),
      respectively) were calculated. Regression analysis was used to assess the
      relationship between gestational age and b0-values as well as calculated ADC
      values. The b0 and ADC values of normal and CDH fetuses were compared with normal
      ranges using the Mann-Whitney U-test. RESULTS: In fetuses with normal lungs,
      there was a negative correlation between gestational age and b0 values as well as
      with ADC(high), a positive correlation with ADC(low) but no correlation with
      ADC(avg). When measurable, ADC(high) values were lower in CDH as compared to
      fetuses with normal lungs and ADC(low) values were higher. ADC(low) was unrelated
      to lung volume. CONCLUSIONS: There is a significant relationship between ADC(low)
      and ADC(high) values and gestational age in normal fetal lungs. This relationship
      is most probably explained by developmental changes during the last three stages
      of lung development, which involve intense peripheral growth of airways and
      vessels as well as maturation. In CDH, measurement of ADC(low) might be useful as
      a predictor of postnatal outcome that is independent of lung volume.

PMID- 19866447
TI  - Alcohol use while on the liver transplant waiting list: a single-center
      experience.
AB  - Alcoholic liver disease (ALD) is a leading indication for liver transplantation.
      Our center has randomly checked blood alcohol levels (BALs) in ALD patients on
      the waiting list since 2004. We aimed to identify the incidence and predictors of
      inactivation on the transplant list due to alcohol use and to determine the
      utility of BAL-screening in this process. We conducted a retrospective review of
      patients with ALD listed for liver transplantation with at least 3 months of
      postlisting follow-up. Alcohol use while on the transplant list was defined as a
      positive BAL, an admission of alcohol use, or refusal to perform screening within
      12 hours of request. Cox proportional hazards regression was used to estimate
      risk ratios (RRs). Of 134 patients meeting eligibility criteria, 78% were male,
      and mean age was 52 years. Alcohol use was documented in 23 patients (17%). Of
      these, 12 refused to have a random screen, 8 had detectable serum ethanol levels,
      and 3 had self-reported alcohol use. On multivariable analysis, a higher number
      of random BAL-checks [RR = 0.63(0.52, 0.76), P = 0.001] and a longer duration of
      prelisting abstinence [RR = 0.88(0.83, 0.94), P = 0.001] independently reduced
      the risk of alcohol use by patients while on the waiting list. None of the
      patients with >24 months of prelisting abstinence had a positive screen. In
      conclusion, this study supports random BAL-screening before transplantation and
      reinforces the importance of abstinence duration as a predictor of relapse. For
      patients with <24 months of prelisting abstinence, our center will increase the
      frequency of random BAL screening and increase the rehabilitation requirements to
      include an intensive 3-week rehabilitation program. We hope that these measures
      will reduce the rate of relapse to alcohol use post-transplantation.

PMID- 19866448
TI  - Hepatitis E virus infection as a cause of graft hepatitis in liver transplant
      recipients.
AB  - Hepatitis E virus (HEV) infection induces self-limiting liver disease in
      immunocompetent individuals. Cases of chronic hepatitis E have recently been
      identified in organ transplant recipients. We questioned if chronic hepatitis E
      plays a role in graft hepatitis after liver transplantation in a low endemic
      area. Two hundred twenty-six liver transplant recipients, 129 nontransplanted
      patients with chronic liver disease, and 108 healthy controls were tested for HEV
      antibodies. HEV RNA was investigated in all sera from transplanted patients. HEV
      antibodies were detected in 1 healthy control (1%), 4 patients with chronic liver
      disease (3%), and 10 liver transplant recipients (4%). Three liver transplant
      patients also tested positive for HEV RNA. Two of them developed persistent
      viremia with HEV genotype 3. The patients were anti-HEV immunoglobulin G-negative
      and HEV RNA-negative before transplantation and had an episode of acute hepatitis
      5 or 7 months after transplantation, which led to advanced liver fibrosis after
      22 months in 1 patient. Seroconversion to anti-HEV occurred not before 4 months
      after the first detection of HEV RNA. The possibility of reverse zoonotic
      transmission was experimentally confirmed by the infection of 5 pigs with a
      patient's serum. The pigs showed histological inflammation in the liver, and HEV
      RNA was detectable in different organs, including muscle. In conclusion, the
      prevalence of HEV infection in Central European liver transplant recipients is
      low; however, chronic hepatitis E may occur and needs to be considered in the
      differential diagnosis of graft hepatitis. The diagnosis of HEV infection should
      be based on HEV RNA determination in immunosuppressed patients. We suggest that
      immunocompromised individuals should avoid eating uncooked meat and contact with
      possibly HEV-infected animals.

PMID- 19866449
TI  - Primary biliary cirrhosis after liver transplantation: influence of
      immunosuppression and human leukocyte antigen locus disparity.
AB  - Patients with primary biliary cirrhosis (PBC), despite excellent outcomes after
      liver transplantation (LT), may develop recurrent primary biliary cirrhosis
      (rPBC). The impact of immunosuppression and HLA mismatches on rPBC is unclear. We
      evaluated 103 consecutive PBC patients who underwent transplantation (follow-up >
      or = 10 months) with serial protocol biopsies. Cox regression was used to
      evaluate factors associated with rPBC: the Model for End-Stage Liver Disease
      score pre-LT, year of transplantation, age and gender of the recipient and donor,
      cold and warm ischemic times, HLA mismatches, rejection, infections, and
      immunosuppression (initial/maintenance). The mean follow-up was 108 months (10
      239 months), rPBC occurred in 36, and the mean was 44 months (10-200 months).
      Immunosuppression was cyclosporine-based in 38 (10 initially on monotherapy) and
      tacrolimus-based in 62 (19 initially on monotherapy). Steroids were discontinued
      in all but 7. Azathioprine was part of the initial immunosuppression in 70, 26
      discontinued it, and 33 were never exposed to it. rPBC was associated
      independently with nonuse/discontinuation of azathioprine (P = 0.015, hazard
      ratio = 0.046, 95% confidence interval = 0.008-0.261). The mean time to rPBC was
      74 months with azathioprine, 43 months when AZA was discontinued, and 31 months
      if no azathioprine was used. Cyclosporine or tacrolimus alone had no impact on
      rPBC, but cyclosporine with azathioprine was protective for rPBC in comparison
      with tacrolimus/azathioprine (0/18 versus 7/25, respectively; P < 0.001). rPBC
      was not affected by HLA mismatches. Azathioprine use in PBC patients who
      underwent transplantation was associated with less disease recurrence and a
      longer time to rPBC. Tacrolimus or cyclosporine individually had no effect, but
      cyclosporine and azathioprine in combination resulted in the least rPBC.

PMID- 19866450
TI  - Focal nodular hyperplasia after orthotopic liver transplantation.
AB  - Focal nodular hyperplasia (FNH) has been well characterized in native livers, but
      to our knowledge, no cases of FNH have been described in liver allografts. We
      review the clinicopathological features of 6 FNHs identified in 4 patients after
      orthotopic liver transplantation. There were 3 male patients and 1 female patient
      ranging in age from 2 to 63 years. The time from transplant to a diagnosis of FNH
      ranged from 15 to 118 months. Two patients presented with an incidental solitary
      liver nodule. One patient presented with 2 liver nodules, and the other patient
      initially presented with 1 liver nodule and was found to have another nodule at
      autopsy 6 years later. Two FNHs were seen as an incidental finding at autopsy,
      and the other 4 were initially identified on ultrasound. Follow-up magnetic
      resonance imaging and computed tomography scans revealed features atypical for
      FNH and suspicious for hepatocellular carcinoma. The initial diagnosis of FNH was
      made by needle core biopsy in 3 cases and at autopsy in 2 cases. The lesions
      ranged in size from 1.7 to 6.9 cm. Three patients had conditions associated with
      altered hepatic vascular perfusion; 2 patients had portal vein thrombosis, and 1
      had a partial allograft from a living donor. In conclusion, FNH can present as a
      hepatic nodule after orthotopic liver transplantation and should not be confused
      with hepatocellular carcinoma. Because of altered hepatic circulation in the
      posttransplant liver, a diagnosis of FNH would not be unexpected. FNH should be
      considered in the differential diagnosis of hepatic nodules within the
      posttransplant liver, especially in patients with known hepatic vascular
      perfusion abnormalities.

PMID- 19866451
TI  - Outcomes for lymphoid malignancies in the Nurses' Health Study (NHS) as compared
      to the Surveillance, Epidemiology and End Results (SEER) Program.
AB  - Vital statistics for the lymphoid malignancies obtained from the Surveillance,
      Epidemiology and End Results (SEER) Program have seldom been directly compared to
      data from alternative national databases. While SEER is recognized as the
      standard, some lymphoid malignancies-especially the chronic ones--may be
      underreported. We compared the incidence, all-cause and cause-specific mortality
      for Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM)
      and chronic lymphocytic leukaemia (CLL) in SEER to that in the Nurses' Health
      Study (NHS), a national cohort study of 121,700 female registered nurses,
      matching for age and race. In over 2.5 million person-years, the incidence of HL
      was the same as in SEER (SIR=1.01 [0.75, 1.26]), while the incidence of NHL, CLL
      and MM were slightly higher. All-cause mortality was lower for the lymphoid
      malignancies except for MM, which was the same; there were no differences in
      cause-specific mortality, except for MM (HR=1.26 [1.07, 1.48]). Our analysis
      suggests that, at least among white women, SEER is a reliable data source with
      respect to lymphoid malignancies.

PMID- 19866453
TI  - No evidence supports vitamin E indiscriminate supplementation.
AB  - For many years, the prevailing concept was that LDL oxidation plays the central
      role in atherogenesis. As a consequence, supplementation of antioxidants,
      particularly vitamin E, became very popular. Unfortunately, major randomized
      clinical trials yielded disappointing results and recent meta-analyses concluded
      that indiscriminate, high dose vitamin E supplementation results in increased
      mortality. This conclusion raised (quite reasonable) criticism, much of which
      referred to the characteristics of meta-analysis. In our recent study, we used a
      Markov-model approach, which is free of most of the limitations of meta-analyses.
      Our major finding was that the average quality-adjusted life years (QALY) of
      vitamin E- supplemented individuals was 0.30 QALY (95%CI 0.21 to 0.39) less than
      that of untreated people. In our view, this supports the view that indiscriminate
      supplementation of high dose vitamin E can not be recommended to the general
      public.In the present communication we address several recent studies that
      demonstrated negative effects of vitamin E and raise possible mechanisms that may
      be responsible for the harmful effects of vitamin E supplementation. We also
      review recent studies conducted with specific groups of patients that gained from
      vitamin E supplementation, indicating that although, on the average,
      indiscriminate supplementation of high dose vitamin E is not beneficial, specific
      populations may gain from vitamin E. The challenge is to establish selection
      criteria that will predict who is likely to benefit from vitamin E
      supplementation. Such criteria may be based either on the assumption that
      antioxidants are likely to be beneficial for people under oxidative stress or on
      knowledge regarding the benefit of sick people with certain diseases. In short,
      we adopt the view that vitamin E is a "double-edge sword" that should not be
      consumed until criteria are defined to predict who is likely to benefit from high
      dose supplementation of vitamin E.

PMID- 19866454
TI  - Synthesis of a molecularly imprinted polymer for the solid-phase extraction of
      betulin and betulinic acid from plane bark.
AB  - INTRODUCTION: Plant extracts are usually complex mixtures of various polarity
      compounds and their study often includes a purification step, such as solid-phase
      extraction (SPE), to isolate interest compounds prior analytical investigations.
      Molecularly imprinted polymers (MIPs) are a new promising type of SPE material
      which offer tailor-made selectivity for the extraction of trace active components
      in complex matrices. Numerous specific cavities that are sterically and
      chemically complementary of the target molecules, are formed in imprinted
      polymers. A molecularly imprinted polymer (MIP) was synthesised in order to trap
      a specific class of triterpene, including betulin and betulinic acid from a
      methanolic extract of plane bark. METHODOLOGY: Imprinted polymers were
      synthesised by thermal polymerisation of betulin as template, methacrylic acid
      (MAA) or acrylamide (AA) as functional monomer, ethylene glycol dimethacrylate as
      crosslinking agent and chloroform as porogen. Afterwards, MAA- and AA-MIPs were
      compared with their non-imprinted polymers (NIPs) in order to assess the
      selectivity vs betulin and its derivatives. Recovered triterpenes were analysed
      by HPLC during MIP-SPE protocol. RESULTS: After SPE optimisation, the MAA
      imprinted polymer exhibited highest selectivity and recovery (better than 70%)
      for betulin and best affinity for its structural analogues. Thus, a selective
      washing step (chloroform, acetonitrile) removed unwanted matrix compounds (fatty
      acids) from the SPE cartridge. The elution solvent was methanol. Finally, the MAA
      MIP was applied to fractionate a plane bark methanolic extract containing betulin
      and betulinic acid. CONCLUSION: This study demonstrated the possibility of direct
      extraction of betulin and its structural analogues from plant extracts by MIP
      technology.

PMID- 19866452
TI  - Silibinin can induce differentiation as well as enhance vitamin D3-induced
      differentiation of human AML cells ex vivo and regulates the levels of
      differentiation-related transcription factors.
AB  - Induction of terminal differentiation is a conceptually attractive approach for
      the therapy of neoplastic diseases. Although vitamin D derivatives (deltanoids)
      can induce differentiation of AML cells in vitro, so far deltanoids have not been
      successfully brought to the clinic, due to the likelihood of life-threatening
      hypercalcemia. Here, we incubated freshly obtained blood cells from patients with
      AML with a plant antioxidant (PAOx), silibinin (SIL), alone or together with a
      deltanoid. Twenty patients with AML (all subtypes except M3) were available for
      this study, and in 14 (70%), SIL (60 uM) either induced differentiation ex vivo,
      or enhanced differentiation induced by deltanoids, or both. Interestingly, SIL
      acting alone induced differentiation only in cases in which chromosome
      aberrations could not be detected. In eleven samples sufficient material was
      available for a limited analysis of the underlying events. Quantitative RT-PCR
      showed that differentiation markers were upregulated at the mRNA level by both
      SIL and deltanoids, suggesting that intracellular signaling pathways upstream of
      transcription factors (TFs) were activated by these agents. Western analysis for
      proteins which function as TFs in deltanoid-induced monocytic differentiation,
      such as members of Jun and C/EBP families, surprisingly demonstrated that SIL
      upregulated all these TFs in the cases tested. This suggests that although the
      presence of SIL may not always be sufficient to induce differentiation, it can
      serve as a differentiation enabling factor for blasts obtained from a large
      proportion of patients with AML. Thus, SIL/deltanoid combinations warrant further
      consideration as preventive/therapeutic regimens in human leukaemia.

PMID- 19866455
TI  - Metabolic profiling of maize mutants deficient for two glutamine synthetase
      isoenzymes using 1H-NMR-based metabolomics.
AB  - INTRODUCTION: Maize mutants deficient for the expression of two genes encoding
      cytosolic glutamine synthetase (GS) isoenzymes GS1.3 and GS1.4 displayed reduced
      kernel number and kernel size, respectively, the effect of the mutation being
      cumulative in the double mutant. However, at maturity, shoot biomass production
      was not modified in all the mutants, indicating that the reaction catalysed by
      the enzyme is specifically involved in the control of grain yield. OBJECTIVE: To
      examine the physiological impact of the GS mutations on the leaf metabolic
      profile during the kernel filling period, during which nitrogen is remobilized
      from the shoots to be further exported to the kernels. METHODOLOGY: An (1)H-NMR
      spectroscopy metabolomic was applied to the investigation of metabolic change of
      the gln1.3, gln1.4 and gln1.3/1.4 double mutant. RESULTS: In the three GS
      mutants, an increase in the amount of several N-containing metabolites such as
      asparagine, alanine, threonine and phophatidylcholine was observed whatever the
      level of nitrogen fertilisation. In addition, we found an accumulation of
      phenylalanine and tyrosine, two metabolites involved the primary steps of the
      phenylpropanoid pathway. CONCLUSION: Changes in the metabolic profile of the GS
      mutants suggest that, when cytosolic GS activity is strongly reduced, either
      alternative metabolic pathways participate in the reassimilation of ammonium
      released during leaf protein remobilization or that premature leaf senescence is
      induced when kernel set and kernel filling are affected. The accumulation of
      phenylalanine and tyrosine in the mutant plants indicates that lignin
      biosynthesis is altered, thus possibly affecting ear development.

PMID- 19866456
TI  - Metabolic response of tomato leaves upon different plant-pathogen interactions.
AB  - INTRODUCTION: Plants utilise various defence mechanisms against their potential
      biotic stressing agents such as viroids, viruses, bacteria or fungi and abiotic
      environmental challenges. Among them metabolic alteration is a common response in
      both compatible and incompatible plant-pathogen interactions. However, the
      identification of metabolic changes associated with defence response is not an
      easy task due to the complexity of the metabolome and the plant response. To
      address the problem of metabolic complexity, a metabolomics approach was employed
      in this study. OBJECTIVE: To identify a wide range of pathogen (citrus exocortis
      viroid, CEVd, or Pseudomonas syringae pv. tomato)-induced metabolites of tomato
      using metabolomics. METHODOLOGY: Nuclear magnetic resonance (NMR) spectroscopy in
      combination with multivariate data analysis were performed to analyse the
      metabolic changes implicated in plant-pathogen interaction. RESULTS: NMR-based
      metabolomics of crude extracts allowed the identification of different
      metabolites implicated in the systemic (viroid) and hypersensitive response
      (bacteria) in plant-pathogen interactions. While glycosylated gentisic acid was
      the most important induced metabolite in the viroid infection, phenylpropanoids
      and a flavonoid (rutin) were found to be associated with bacterial infection.
      CONCLUSIONS: NMR metabolomics is a potent platform to analyse the compounds
      involved in different plant infections. A broad response to different pathogenic
      infections was revealed at metabolomic levels in the plant. Also, metabolic
      specificity against each pathogen was observed.

PMID- 19866458
TI  - New and old concepts in thermoelectric materials.
AB  - Herein we cover the key concepts in the field of thermoelectric materials
      research, present the current understanding, and show the latest developments.
      Current research is aimed at increasing the thermoelectric figure of merit (ZT)
      by maximizing the power factor and/or minimizing the thermal conductivity.
      Attempts at maximizing the power factor include the development of new materials,
      optimization of existing materials by doping, and the exploration of nanoscale
      materials. The minimization of the thermal conductivity can come through solid
      solution alloying, use of materials with intrinsically low thermal conductivity,
      and nanostructuring. Herein we describe the most promising bulk materials with
      emphasis on results from the last decade. Single-phase bulk materials are
      discussed in terms of chemistry, crystal structure, physical properties, and
      optimization of thermoelectric performance. The new opportunities for enhanced
      performance bulk nanostructured composite materials are examined and a look into
      the not so distant future is attempted.

PMID- 19866459
TI  - Metabolomic analysis of host plant resistance to thrips in wild and cultivated
      tomatoes.
AB  - INTRODUCTION: Western flower thrips (Frankliniella occidentalis) are among the
      most serious crop pests worldwide. Control of thrips mainly depends on
      pesticides, excessive use of which leads to human health risks and environmental
      contamination. As an alternative, we study host plant resistance to thrips.
      OBJECTIVE: To apply nuclear magnetic resonance spectroscopy (NMR) metabolomics to
      study host plant resistance to thrips in wild and cultivated tomatoes.
      METHODOLOGY: Ten wild species and 10 cultivated tomato lines were compared. Five
      replicates of each species and lines were used for a thrips bioassay while
      another five replicates were used for the metabolomic analysis. The three most
      resistant and susceptible wild species, and cultivated lines, as identified by
      the thrips bioassay, were used for the metabolomics, performed by (1)H NMR
      spectroscopy followed by principal component analysis. RESULTS: Wild and
      cultivated tomatoes differed significantly in thrips resistance. Only wild
      tomatoes were thrips-resistant, among which Lycopersicon pennellii and L.
      hirsutum exhibited the lowest thrips damage. Their (1)H NMR-based metabolomic
      profiles were significantly different from those of thrips-susceptible tomatoes.
      Thrips-resistant tomatoes contained acylsugars, which are known for their
      negative effect on herbivores. CONCLUSION: The identification of acylsugars as a
      resistance factor for thrips in tomato proves that NMR-based metabolomics an
      important tool to study plant defences, providing fundamental information for the
      development and realisation of herbivore resistance breeding programmes in
      agricultural crops.

PMID- 19866461
TI  - Phthalocyanine-C60 fused conjugates exhibiting molecular orbital interactions
      depending on the solvent polarity.
AB  - New covalently C60-connected zinc phthalocyanine (ZnPc) derivatives have been
      synthesized by utilizing successive cycloaddition reactions of C60 with a ZnPc
      derivative containing a pyridazine moiety employing Komatsu's method in reaction
      of C60 with phthalazine. The UV/Vis absorption spectrum of the fused conjugate
      (5) shows red shifts from the corresponding absorption of ZnPc derivative (8),
      indicating interactions between the ZnPc and C60 moieties. The DFT calculations
      under non-polar medium predict that the HOMO and LUMO of 5 localize on the ZnPc
      moiety, whereas LUMO+1 localizes on the C60 moiety, which reasonably explain the
      magnetic circular dichroism (MCD) and absorption spectra in toluene.
      Electrochemical redox potentials of 5 in polar solvents indicate the first
      oxidation potential arises from the ZnPc moiety, whereas the first reduction
      potential is associated with the C60 moiety, suggesting the LUMO localizes on the
      C60 moiety in polar solvent. This reversal of the LUMO is supported by the ZnPc
      fluorescence quenching with a nearby C60 moiety in benzonitrile, which leads to
      the charge-separation via the excited singlet state of the ZnPc moiety. In
      toluene on the other hand, such a ZnPc-fluorescence quenching owing to the
      photoinduced charge separation is not observed as predicted by the DFT-calculated
      LUMO on the ZnPc moiety.

PMID- 19866464
TI  - Leukocytic promotion of prostate cellular proliferation.
AB  - BACKGROUND: Histological evidence of pervasive inflammatory infiltrate has been
      noted in both benign prostatic hyperplasia/hypertrophy (BPH) and prostate cancer
      (PCa). Cytokines known to attract particular leukocyte subsets are secreted from
      prostatic stroma consequent to aging and also from malignant prostate epithelium.
      Therefore, we hypothesized that leukocytes associated with either acute or
      chronic inflammation attracted to the prostate consequent to aging or
      tumorigenesis may promote the abnormal cellular proliferation associated with BPH
      and PCa. METHODS: An in vitro system designed to mimic the human prostatic
      microenvironment incorporating prostatic stroma (primary and immortalized
      prostate stromal fibroblasts), epithelium (N15C6, BPH-1, LNCaP, and PC3 cells),
      and inflammatory infiltrate (HL-60 cells, HH, and Molt-3 T-lymphocytes) was
      developed. Modified Boyden chamber assays were used to test the ability of
      prostate stromal and epithelial cells to attract leukocytes and to test the
      effect of leukocytes on prostate cellular proliferation. Antibody arrays were
      used to identify leukocyte-secreted cytokines mediating prostate cellular
      proliferation. RESULTS: Leukocytic cells migrated towards both prostate stromal
      and epithelial cells. CD4+ T-lymphocytes promoted the proliferation of both
      transformed and non-transformed prostate epithelial cell lines tested, whereas
      CD8+ T-lymphocytes as well as dHL-60M macrophagic and dHL-60N neutrophilic cells
      selectively promoted the proliferation of PCa cells. CONCLUSIONS: The results of
      these studies show that inflammatory cells can be attracted to the prostate
      tissue microenvironment and can selectively promote the proliferation of non
      transformed or transformed prostate epithelial cells, and are consistent with
      differential role(s) for inflammatory infiltrate in the etiologies of benign and
      malignant proliferative disease in the prostate.

PMID- 19866465
TI  - Alterations in cholesterol regulation contribute to the production of
      intratumoral androgens during progression to castration-resistant prostate cancer
      in a mouse xenograft model.
AB  - BACKGROUND: Emerging evidence suggests that androgens and the androgen receptor
      (AR) are important mediators of castration-resistant prostate cancer (CRPC)
      progression. Increased expression of several enzymes responsible for cholesterol
      synthesis and conversion into downstream androgens has been documented in human
      CRPC tumors in comparison to primary tumors. Based on these observations it is
      hypothesized that cholesterol and its overall regulation within the cell are
      altered, thus modifying precursor levels for de novo androgen synthesis within
      the castrate tumoral environment. METHODS: Tumoral steroid levels were assessed
      by LC-MS. Free and esterified cholesterol was quantified by LC-MS and a
      fluorescent assay. Gene and protein expression were assessed by RT-PCR and
      immunoblotting. RESULTS: Herein, using a prostate cancer xenograft mouse model it
      is demonstrated by Western blot analysis that proteins responsible for
      cholesterol regulation (LDL-r, SR-B1, HMG-CoA reductase, ACAT1,2, ABCA1) are
      altered during disease progression to increase influx and synthesis of
      cholesterol as well as free cholesterol formation from cholesteryl ester stores.
      In turn this can provide increased amounts of precursor for intratumoral
      steroidogenesis after castration. Androgens- testosterone and dihydrotestosterone
      coincidently increase at CRPC to physiologically relevant levels leading to the
      induction of AR expression and PSA production. Furthermore, cellular cholesterol
      homeostasis is maintained by increased cholesterol efflux at CRPC so that excess
      free cholesterol does not cause toxicity to the tumor cells. CONCLUSIONS:
      Cellular cholesterol regulation processes are altered during progression to CRPC.
      Free cholesterol from increased biosynthesis or uptake is likely a precursor for
      intratumoral de novo androgen synthesis.

PMID- 19866466
TI  - Investigation of acrylamide formation on bakery products using a crust-like
      model.
AB  - Baking is a complex process where a temperature gradient occurs within the
      product as a result of simultaneous heat and mass transfers. This behaviour makes
      the physical parameters (baking temperature and product dimensions) as effective
      as the chemical parameters on the rate of acrylamide formation in bakery foods.
      In this study, the change of temperature in different locations of the sample was
      shown as influenced by the product thickness. The temperature values were close
      to each other in the sample having thickness of 1 mm (crust model). The product
      temperature rapidly increased to the oven temperature. A temperature gradient was
      recorded in the sample having a thickness of 10 mm. As a result, the product
      temperature did not exceed 100 degrees C within a baking time of 30 min. The
      product thickness significantly influenced the rate of acrylamide formation
      during baking. Acrylamide concentration rapidly increased to 411+/-49 ng/g within
      8 min in the crust model sample. However, no acrylamide was detected in the
      thicker sample within 15 min under the same conditions, because the moisture
      content was still above 10%. The crust model was considered useful to test the
      effectiveness of different mitigation strategies in bakery foods.

PMID- 19866467
TI  - Peanut varieties with reduced Ara h 1 content indicating no reduced
      allergenicity.
AB  - Peanut allergy is a major cause of food-induced severe anaphylactic reactions. To
      date, no medical care is available to prevent and treat peanut allergy and
      therefore hypoallergenic peanut varieties are of considerable health political
      and economic interest. Major allergens that induce IgE-responses in peanut
      sensitive patients are Ara h 1, Ara h 2 and Ara h 3/4. In order to identify
      hypoallergenic peanuts, commercially locally available peanut varieties were
      screened for their allergen content. Ara h 1-deficient peanuts from Southeast
      Asia were identified by SDS-PAGE, immunoblotting, inhibition assays and ELISA. 2
      D PAGE analyses demonstrated the different compositions of the tested extracts
      and revealed a number of variations of the allergen patterns of peanuts from
      different varieties. Mediator release experiments of these peanut extracts
      demonstrated similar allergenicities as compared with standard peanut extract.
      These results indicate that the allergenicity of peanuts with reduced Ara h 1
      content might be compensated by the other allergens, and thus do not necessarily
      cause a reduction of allergenicity.

PMID- 19866468
TI  - Repeated oral administration modulates the pharmacokinetic behavior of the
      chemopreventive agent phenethyl isothiocyanate in rats.
AB  - The principal objective of this study was to evaluate whether repeated oral
      administration influences the pharmacokinetic behavior of the chemopreventive
      agent phenethyl isothiocyanate (PEITC) in rat. Animals were treated orally with
      0.5, 1.0 and 5.0 mg/kg of the isothiocyanate for 4 days, and plasma levels at
      various times post-administration were determined by LC/MS after the first and
      last day. To determine absolute bioavailability, a group of animals was treated
      with a single (0.5 mg/kg) intravenous dose of PEITC. Following single oral dose
      administration, PEITC was rapidly absorbed, peak plasma concentrations being
      attained within the hour, and achieved an absolute bioavailability of 77%, but
      displayed dose-dependent pharmacokinetics, with bioavailability decreasing and
      clearance increasing moderately with dose; C(max) values did not rise
      proportionately to the dose and volume of distribution increased. At the higher
      doses of 1.0 and 5.0 mg/kg, repeated administration led to higher PEITC plasma
      C(max) concentrations and decreased plasma clearance of the isothiocyanate
      leading to enhanced bioavailability.

PMID- 19866470
TI  - Dietary apple polyphenols have preventive effects against lengthening contraction
      induced muscle injuries.
AB  - We examined whether polyphenols from dietary apple have protective effects
      against exercise-induced muscle strain injury. Sixteen male Wistar rats were
      randomly assigned into the apple polyphenol (APP; N=8) and control (CON; N=8)
      groups. The APP and the CON groups were fed diets with and without 5% APP,
      respectively. After a 3-wk feeding period, the gastrocnemii of the animals were
      subject to lengthening contractions with electrical stimulation and forced ankle
      dorsiflexion. Isometric torques were measured before and after the lengthening
      contractions and on days 1, 2, 3, 5, and 7 after the contractions. On day 7, the
      animals were sacrificed and the gastrocnemii harvested. Thiobarbituric-acid
      reactive substances, protein carbonyl, and mRNA of antioxidative proteins in the
      muscles were quantified. The APP group had significantly lower torque deficits
      than the CON group on days 3, 5, and 7 after the eccentric contractions. The
      thiobarbituric-acid-reactive substances and protein carbonyl levels in the case
      of the APP group were significantly lower than those in the case of the CON
      group. The APP group had significantly higher glutathione-S-transferase alpha1
      mRNA levels than the CON group. Therefore, we conclude that dietary APPs have
      protective effects against lengthening contraction-induced muscle injury.

PMID- 19866469
TI  - The expression of osteoclastogenesis-associated factors and osteoblast response
      to osteolytic prostate cancer cells.
AB  - BACKGROUND: Prostate cancer (PCa) has a propensity to metastasize to bone. Tumor
      cells replace bone marrow and can elicit an osteoblastic, osteolytic, or mixed
      bone response. Our objective was to elucidate the mechanisms and key factors
      involved in promoting osteoclastogenesis in PCa bone metastasis. METHODS: We
      cultured osteoblast-like MC3T3-E1 cells with conditioned medium (CM) from PC-3
      and C4-2B cells. MC3T3-E1 mineralization decreased in the presence of PC-3 CM,
      whereas C4-2B CM had no effect on mineralization. Using oligo arrays and
      validating by real-time PCR, we observed a decrease in the expression of
      mineralization-associated genes in MC3T3-E1 cells grown in the presence of PC-3
      CM. In addition, PC-3 CM induced the expression of osteoclastogenesis-associated
      genes IGFBP-5, IL-6, MCP-1, and RANKL while decreasing OPG expression in MC3T3-E1
      cells. Furthermore, CM from MC3T3-E1 cells cultured in the presence of PC-3 CM,
      in association with soluble RANKL, increased osteoclastogenesis in RAW 264.7
      cells. Investigation of PCa metastases and xenografts by immunohistochemistry
      revealed that the osteoclastic factor IL-6 was expressed in the majority of PCa
      bone metastases and to a lesser extent in PCa soft tissue metastases. In vitro it
      was determined that soluble IL-6R (sIL-6R) was necessary for IL-6 to inhibit
      mineralization in MC3T3-E1 cells. RESULTS: PC-3 cells inhibit osteoblast activity
      and induce osteoblasts to produce osteoclastic factors that promote
      osteoclastogenesis, and one of these factors, IL-6, is highly expressed in PCa
      bone metastases. CONCLUSIONS: IL-6 may have an important role in promoting
      osteoclastogenesis in PCa bone metastasis through its' interaction with sIL-6R.

PMID- 19866471
TI  - Vitamin E tocotrienols improve insulin sensitivity through activating peroxisome
      proliferator-activated receptors.
AB  - Vitamin E is comprised of two classes of compounds: tocopherols and tocotrienols.
      Tocotrienol-enriched palm oil has been shown to help reduce blood glucose levels
      in patients and preclinical animal models. However, the mechanistic basis for
      tocotrienol action is not well established. Peroxisome proliferator-activated
      receptors alpha, gamma, and delta (PPARalpha, PPARgamma, and PPARdelta) are
      ligand-regulated transcription factors that play essential roles in energy
      metabolism. Importantly, synthetic PPARalpha and PPARgamma ligands are currently
      used for treating hyperlipidemia and diabetes. In this study, we present data
      that tocotrienols within palm oil functioned as PPAR modulators. Specifically,
      both alpha- and gamma-tocotrienol activated PPARalpha, while delta-tocotrienol
      activated PPARalpha, PPARgamma, and PPARdelta in reporter-based assays.
      Tocotrienols enhanced the interaction between the purified ligand-binding domain
      of PPARalpha with the receptor-interacting motif of coactivator PPARgamma
      coactivator-1alpha. In addition, the tocotrienol-rich fraction of palm oil
      improved whole body glucose utilization and insulin sensitivity of diabetic Db/Db
      mice by selectively regulating PPAR target genes. These lines of evidence
      collectively suggested that PPARs represent a set of molecular targets of
      tocotrienols.

PMID- 19866472
TI  - Overexpression of hepatocyte nuclear factor-3alpha induces apoptosis through the
      upregulation and accumulation of cytoplasmic p53 in prostate cancer cells.
AB  - BACKGROUND: Hepatocyte nuclear factor-3alpha (HNF-3alpha) has been known to act
      as a repressor in the pathogenesis of many cancers. Herein, we investigated the
      effect of HNF-3alpha overexpression in prostate cancer cells. METHODS: HNF-3alpha
      was overexpressed in prostate cancer cells using an adenovirus recombinant
      expressing wild-type HNF-3alpha. The apoptosis of prostate cancer cells was
      determined by TUNEL, FACS, and caspase activity analyses. RESULTS: Adenovirus
      mediated overexpression of HNF-3alpha caused cell death in prostate cancer cells
      as assessed by changes in cellular and nuclear morphology, TUNEL analysis, and
      caspase activations. Furthermore, FACS analysis showed an increased sub-G1 phase
      of cell cycle as well as the G2/M phase with a corresponding decrease in S
      phases. HNF-3alpha overexpression caused the upregulation of p53 protein and its
      accumulation, together with HNF-3alpha, in the cytoplasm. It also causes Bax
      protein to localize to the mitochondria-enriched fraction. These findings suggest
      that multiple apoptotic pathways seem to be involved in the HNF-3alpha-induced
      cell death: pathways involving the accumulation of p53 protein in the cytoplasm
      and subsequent cytochrome c release, and other pathways involving death receptor
      signaling and caspase-8 activation. CONCLUSIONS: The results of the current study
      suggest a novel function of HNF-3alpha as a killer of malignant prostate cancer
      cells, which reveals HNF-3alpha as a promising therapeutic molecule for prostate
      cancers.

PMID- 19866473
TI  - Association of 17 prostate cancer susceptibility loci with prostate cancer risk
      in Chinese men.
AB  - BACKGROUND: Several genome-wide association studies (GWAS) in populations of
      European descent have identified more than a dozen common genetic variants that
      are associated with prostate cancer risk. METHODS: To determine whether these
      variants are also associated with prostate cancer risk in the Chinese population,
      we evaluated 17 prostate cancer susceptibility loci in a population-based case
      control study from Shanghai, including 288 prostate cancer cases and 155
      population controls. RESULTS: After adjustment for age, two of the 17 loci were
      significantly associated with prostate cancer risk, while the other 15 loci were
      suggestively associated with prostate cancer risk in this population. The
      strongest associations were found for chromosome 8q24 Region 2 (rs1016343: OR =
      2.07, 95% CI: 1.35-3.20, P = 9.4 x 10(-4)) and 8q24 Region 1 (rs10090154: OR =
      2.07, 95% CI: 1.31-3.28, P = 0.002); additional single nucleotide polymorphisms
      (SNPs) assessed in these two 8q24 regions were also significant (OR(Region2) =
      1.92-2.05, P = 9.4 x 10(-4) to 0.003, and OR(Region1) = 1.77-1.81, P = 0.01 for
      all SNPs). CONCLUSIONS: Our study shows that multiple prostate cancer risk loci
      identified in European populations by GWAS are also associated with prostate
      cancer risk in Chinese men, a low-risk population with mostly clinically relevant
      cancers. Larger studies in Chinese and Asian populations are needed to confirm
      these findings and the role of these risk loci in prostate cancer etiology in
      Asian men.

PMID- 19866474
TI  - Pulsed electromagnetic fields accelerate proliferation and osteogenic gene
      expression in human bone marrow mesenchymal stem cells during osteogenic
      differentiation.
AB  - Osteogenesis is a complex series of events involving the differentiation of
      mesenchymal stem cells to generate new bone. In this study, we examined the
      effect of pulsed electromagnetic fields (PEMFs) on cell proliferation, alkaline
      phosphatase (ALP) activity, mineralization of the extracellular matrix, and gene
      expression in bone marrow mesenchymal stem cells (BMMSCs) during osteogenic
      differentiation. Exposure of BMMSCs to PEMFs increased cell proliferation by
      29.6% compared to untreated cells at day 1 of differentiation. Semi-quantitative
      RT-PCR indicated that PEMFs significantly altered temporal expression of
      osteogenesis-related genes, including a 2.7-fold increase in expression of the
      key osteogenesis regulatory gene cbfa1, compared to untreated controls. In
      addition, exposure to PEMFs significantly increased ALP expression during the
      early stages of osteogenesis and substantially enhanced mineralization near the
      midpoint of osteogenesis. These results suggest that PEMFs enhance early cell
      proliferation in BMMSC-mediated osteogenesis, and accelerate the osteogenesis.

PMID- 19866476
TI  - Curvilinear electronics formed using silicon membrane circuits and elastomeric
      transfer elements.
AB  - Materials and methods to achieve electronics intimately integrated on the
      surfaces of substrates with complex, curvilinear shapes are described. The
      approach exploits silicon membranes in circuit mesh structures that can be
      deformed in controlled ways using thin, elastomeric films. Experimental and
      theoretical studies of the micromechanics of such curvilinear electronics
      demonstrate the underlying concepts. Electrical measurements illustrate the high
      yields that can be obtained. The results represent significant experimental and
      theoretical advances over recently reported concepts for creating hemispherical
      photodetectors in electronic eye cameras and for using printable silicon
      nanoribbons/membranes in flexible electronics. The results might provide
      practical routes to the integration of high performance electronics with
      biological tissues and other systems of interest for new applications.

PMID- 19866475
TI  - CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel
      induced cytotoxicity.
AB  - BACKGROUND: Metastatic prostate cancer is either inherently resistant to
      chemotherapy or rapidly acquires this phenotype after chemotherapy exposure. In
      this study, we identified a docetaxel-induced resistance mechanism centered on
      CCL2. METHODS: We compared the gene expression profiles in individual human
      prostate cancer specimens before and after exposure to chemotherapy collected
      from previously untreated patients who participated in a clinical trial of
      preoperative chemotherapy. Subsequently, we used the gain- and loss-of-function
      approach in vitro to identify a potential mechanism underlying chemotherapy
      resistance. RESULTS: Among the molecular signatures associated with treatment,
      several genes that regulate the inflammatory response and chemokine activity were
      upregulated including a significant increase in transcripts encoding the CC
      chemokine CCL2. Docetaxel increased CCL2 expression in prostate cancer cell lines
      in vitro. CCL2-specific siRNA inhibited LNCaP and LAPC4 cell proliferation and
      enhanced the growth inhibitory effect of low-dose docetaxel. In contrast,
      overexpression of CCL2 or recombinant CCL2 protein stimulated prostate cancer
      cell proliferation and rescued cells from docetaxel-induced cytotoxicity. This
      protective effect of CCL2 was associated with activation of the ERK/MAP kinase
      and PI3K/AKT, inhibition of docetaxel-induced Bcl2 phosphorylation at serine 70,
      phosphorylation of Bad, and activation of caspase-3. The addition of a PI3K/AKT
      inhibitor Ly294002 reversed the CCL2 protection and was additive to docetaxel
      induced toxicity. CONCLUSION: These results support a mechanism of chemotherapy
      resistance mediated by cellular stress responses involving the induction of CCL2
      expression and suggest that inhibiting CCL2 activity could enhance therapeutic
      responses to taxane-based therapy.

PMID- 19866480
TI  - Combination of alpha-1 antitrypsin and doxycycline suppresses collagen-induced
      arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a complex disease characterized by
      autoimmune inflammation and joint destruction. Despite recent advances in RA
      treatment, current therapies require further improvement to overcome adverse
      events and ineffectiveness in some cases. By targeting different
      pathways/molecules using drug combinations, a better treatment can be obtained,
      whereas adverse events are reduced. In order to develop a new treatment option,
      the present study employs a gene therapy-based combination therapy using
      doxycycline and human alpha-1 antitrypsin (hAAT). METHODS: DBA/1 mice were
      immunized with type II collagen to induce arthritis. Four weeks before
      immunization, they received a doxycycline containing diet and a single injection
      of adeno-associated virus vector expressing hAAT under the control of a
      tetracycline-dependent promoter. Control groups received doxycycline alone or
      saline. Macroscopic arthritis development as well as histopathological changes in
      the joint were evaluated. In addition, the effects of hAAT and doxycycline on
      lipopolysaccharide (LPS)- or tumor necrosis factor-alpha-induced interleukin (IL)
      6 production from mouse fibroblast cells were also determined. RESULTS:
      Combination therapy significantly reduced arthritis development and progression
      compared to the control group in respect to macroscopic as well as
      histopathological changes. Doxycycline and hAAT in combination also inhibited IL
      6 expression from LPS-stimulated NIH/3T3 mouse fibroblast cells, indicating a
      contributing mechanism of arthritis inhibition. CONCLUSIONS: The results obtained
      in the present study indicate that a combination therapy using AAT and
      doxycycline holds promising potential as a new therapy for RA.

PMID- 19866481
TI  - Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10
      and interleukin-12 gene therapy on airway inflammation in asthmatic mice.
AB  - BACKGROUND: Asthma is a chronic disease characterized by airway inflammation
      caused by the dysregulated production of cytokines secreted by allergen-specific
      type 2 T helper (Th2) cells. Although the Th1-promoting cytokine, interleukin
      (IL)-12, is capable of inhibiting Th2-driven allergen-induced airway changes in
      mice, IL-12 also aggravates the Th1-driven inflammatory pulmonary pathology.
      Further, IL-10 was found to exert both anti-inflammatory and immunoregulatory
      activities. To avoid the side-effects of IL-12, we hypothesized that the low-dose
      expression of IL-10 with concomitant IL-12 administration in the airway may
      represent a more effective therapy for allergic airway diseases. Thus, the
      present study explored the immunomodulatory and therapeutic effects of IL-10
      combined with IL-12 in airway inflammation in allergic asthma. METHODS:
      Adenovirus-expressing murine IL-10 (Ad-IL-10) and IL-12 (Ad-IL-12) were co
      administrated in an established murine model of ovalbumin (OVA)-induced asthma.
      RESULTS: We found that a single combined treatment of low doses of Ad-IL-10 and
      Ad-IL-12 efficiently inhibited the development of airway hyper-responsiveness
      compared to Ad-IL-10 or Ad-IL-12 treatment alone. Moreover, both Ad-IL-10 and Ad
      IL-12 treatment reduced pulmonary infiltration of eosinophils and neutrophils. In
      addition, histological studies showed that combined treatment was able to reduce
      tumor necrosis factor-alpha-mediated airway inflammation induced by IL-12
      treatment. Suppression of IL-4, IL-5, Keratinocyte-derived chemokine (KC) and
      eotaxin in bronchoalveolar lavage fluid was also noted in OVA-immunized mice with
      combined Ad-IL-10 and Ad-IL-12 treatment. CONCLUSIONS: Taken together, the
      results obtained in the present study indicate that co-administration of IL-12
      and IL-10 may have therapeutic potential for the immunomodulatory treatment of
      allergic asthma.

PMID- 19866482
TI  - Immunization with a DNA vaccine candidate in chronic hepatitis C patients is
      safe, well tolerated and does not impair immune response induction after anti
      hepatitis B vaccination.
AB  - BACKGROUND: In the present study, we evaluated the safety of CIGB-230, a novel
      vaccine candidate based on the mixture of a plasmid for DNA immunization,
      expressing hepatitis C virus (HCV) structural antigens, with a recombinant HCV
      Core protein. METHODS: Fifteen HCV chronically-infected volunteers with
      detectable levels of HCV RNA genotype 1b, who were nonresponders to previous
      treatment with interferon plus ribavirin, were intramuscularly injected with CIGB
      230 on weeks 0, 4, 8, 12, 16 and 20. Individuals were also immunized at weeks 28,
      32 and 36 with a recombinant vaccine against hepatitis B. Adverse events were
      recorded and analyzed. Blood samples were taken every 4 weeks up to month 12 for
      hematological, biochemical, virological and immunological analysis. RESULTS: All
      patients completed the treatment with CIGB-230. Adverse events were only slight
      (83.6%) or moderate (16.4%). No significant differences in hematological and
      biochemical parameters, including serum aminotransferases, were detected between
      the baseline and post-treatment state. Induction of a CD4+ T lymphocyte response
      against a particular region in HCV E1, spanning amino acids 230-312 in HCV
      polyprotein, was detected in 42.8% of patients during treatment with CIGB-230.
      The ability of T cells to proliferate in response to mitogenic stimulation was
      not weakened. Most individuals (78.6%) were seroprotected after anti-hepatitis B
      vaccination and 42.8% were hyper-responders (antibody titers > 100 UI/ml). No
      anti-mitochondrial, anti-nuclear and anti-extractable nuclear antigen antibodies
      were generated during immunization with CIGB-230. CONCLUSIONS: Vaccination with
      CIGB-230 in HCV chronically-infected individuals was safe, well tolerated and did
      not impair the ability to respond to non-HCV antigens.

PMID- 19866483
TI  - Migration of allosensitizing donor myeloid dendritic cells into recipients after
      liver transplantation.
AB  - It is thought, but there is no evidence, that myeloid dendritic cells (MDCs) of
      donor origin migrate into the recipient after clinical organ transplantation and
      sensitize the recipient's immune system by the direct presentation of donor allo
      antigens. Here we show prominent MDC chimerism in the recipient's circulation
      early after clinical liver transplantation (LTx) but not after renal
      transplantation (RTx). MDCs that detach from human liver grafts produce large
      amounts of pro-inflammatory [tumor necrosis factor alpha and interleukin 6 (IL
      6)] and anti-inflammatory (IL-10) cytokines upon activation with various stimuli,
      express higher levels of toll-like receptor 4 than blood or splenic MDCs, and are
      sensitive to stimulation with a physiological concentration of lipopolysaccharide
      (LPS). Upon stimulation with LPS, MDCs detaching from liver grafts prime
      allogeneic T cell proliferation and production of interferon gamma but not of IL
      10. Soluble factors secreted by liver graft MDCs amplify allogeneic T helper 1
      responses. In conclusion, after clinical LTx, but not after RTx, prominent
      numbers of donor-derived MDCs migrate into the recipient's circulation. MDCs
      detaching from liver grafts produce pro-inflammatory and anti-inflammatory
      cytokines and are capable of stimulating allogeneic T helper 1 responses, and
      this suggests that MDC chimerism after clinical LTx may contribute to liver graft
      rejection rather than acceptance.

PMID- 19866484
TI  - Hepatitis C virus infection after liver transplantation is associated with lower
      levels of activated CD4(+)CD25(+)CD45RO(+)IL-7ralpha(high) T cells.
AB  - The expression of interleukin 7 receptor alpha(high) (IL-7Ralpha(high))
      discriminates between activated CD25(+)CD45RO(+)CD4(+) T cells [IL-7Ralpha(high)
      and forkhead box P3-negative (FoxP3(-))] and regulatory T cells (IL-7Ralpha(low)
      and FoxP3(+)). The IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell
      population has been shown to be expanded in the blood and tissues of patients
      after kidney transplantation and to contain alloreactive T cells (activated T
      cells). In the present study, we analyzed the distribution of IL
      7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cells in the blood of 53 patients
      after liver transplantation. The IL-7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T
      cell population was significantly expanded (P < 0.0001) in stable transplant
      recipients versus healthy donors. However, the magnitude of the expansion was
      significantly higher (P < 0.0001) in liver transplant recipients with no
      hepatitis C virus (HCV) infection in comparison with those with a preexisting HCV
      infection. Interestingly, effective suppression of HCV viremia after antiviral
      therapy was associated with an increase in the IL
      7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population to levels
      comparable to those of liver transplant recipients not infected with HCV. The
      present results indicate that (1) the IL
      7Ralpha(high)CD25(+)CD45RO(+)CD4(+)FoxP3(-) T cell population is expanded after
      liver transplantation, (2) it is a valuable immunological marker for monitoring
      activated and potential alloreactive CD4 T cells in liver transplantation, and
      (3) a preexisting HCV infection negatively influences the expansion of this
      population in liver transplant recipients.

PMID- 19866486
TI  - HOP is a monomer: investigation of the oligomeric state of the co-chaperone HOP.
AB  - The co-chaperone Hsp70-Hsp90 organizing protein (HOP) plays a central role in
      protein folding in vivo, binding to both Hsp70 and Hsp90 and bringing them
      together in a functional complex. Reports in the literature concerning the
      oligomeric state of HOP have been inconsistent-is it a monomer, dimer, or higher
      order oligomer? Knowing the oligomeric state of HOP is important, because it
      places limits on the number and types of multiprotein complexes that can form
      during the folding cycle. Thus, the number of feasible models is simplified.
      Here, we explicitly investigate the oligomeric state of HOP using three
      complementary methods: gel filtration chromatography, sedimentation equilibrium
      analytical ultracentrifugation (AUC), and an in vivo coexpression assay. We find
      that HOP does not behave like a monomeric globular protein on gel filtration.
      Rather its behavior is consistent with it being either an elongated monomer or a
      dimer. We follow-up on these studies using sedimentation equilibrium AUC, which
      separates on the basis of molecular weight (MW), independent of shape.
      Sedimentation equilibrium AUC clearly shows that HOP is a monomer, with no
      indication of higher MW species. Finally, we use an in vivo coexpression assay
      that also supports the conclusion that HOP is a monomer.

PMID- 19866485
TI  - The prolyl isomerase domain of PpiD from Escherichia coli shows a parvulin fold
      but is devoid of catalytic activity.
AB  - PpiD is a periplasmic folding helper protein of Escherichia coli. It consists of
      an N-terminal helix that anchors PpiD in the inner membrane near the SecYEG
      translocon, followed by three periplasmic domains. The second domain (residues
      264-357) shows homology to parvulin-like prolyl isomerases. This domain is a well
      folded, stable protein and follows a simple two-state folding mechanism. In its
      solution structure, as determined by NMR spectroscopy, it resembles most closely
      the first parvulin domain of the SurA protein, which resides in the periplasm of
      E. coli as well. A previously reported prolyl isomerase activity of PpiD could
      not be reproduced when using improved protease-free peptide assays or assays with
      refolding proteins as substrates. The parvulin domain of PpiD interacts, however,
      with a proline-containing tetrapeptide, and the binding site, as identified by
      NMR resonance shift analysis, colocalized with the catalytic sites of other
      parvulins. In its structure, the parvulin domain of PpiD resembles most closely
      the inactive first parvulin domain of SurA, which is part of the chaperone unit
      of this protein and presumably involved in substrate recognition.

PMID- 19866487
TI  - Enhanced red-emitting railroad worm luciferase for bioassays and bioimaging.
AB  - A luciferase from the railroad worm (Phrixothrix hirtus) is the only red-emitting
      bioluminescent enzyme in nature that is advantageous in multicolor luciferase
      assays and in bioluminescence imaging (BLI). However, it is not used widely in
      scientific or industrial applications because of its low activity and stability.
      By using site-directed mutagenesis, we produced red-emitting mutants with higher
      activity and better stability. Compared with the wild-type (WT), the luminescent
      activities from extracts of cultured mammalian cells expressing mutant luciferase
      were 9.8-fold in I212L/N351K, 8.4-fold in I212L, and 7.8-fold in I212L/S463R; and
      the cell-based activities were 3.6-fold in I212L/N351K and 3.4-fold in N351K. The
      remaining activities after incubation at 37 degrees C for 10 min were 50.0% for
      I212L/S463R, 31.8% for I212L, and 23.0% for I212L/N351K, but only 5.2% for WT. To
      demonstrate an application of I212L/N351K, cell-based BLI was performed, and the
      luminescence signal was 3.6-fold higher than in WT. These results indicate that
      the mutants might improve the practicability of this signaling in bioassays and
      BLI.

PMID- 19866489
TI  - Physiological effects of high- and low-voltage pulse combinations for gene
      electrotransfer in muscle.
AB  - Gene transfer by electroporation is gaining momentum now that high-level, long
      term expression of transgenes is being obtained. Several different pulse regimens
      are efficient, yet little information is available about the physiological
      muscular response to gene electrotransfer. This paper provides a comprehensive
      evaluation of the physiological and molecular effects on host tissue after DNA
      electrotransfer. We have tested several pulse regimens with special emphasis on
      the pulse combination of a short (100 microsec) high-voltage (HV) pulse followed
      by a long low-voltage (LV) pulse used for DNA electrotransfer, comparing it with
      8 HV pulses designed to ensure extensive permeabilization of the muscle membrane.
      Using both mouse and rat skeletal muscle tissue, we investigated cell
      permeabilization by the 51Cr-labeled EDTA assay, lactate dehydrogenase release,
      Na+ and Ca2+ influx, K+ efflux, ATP release, and water content, as well as muscle
      function both in vivo and ex vivo, Hsp70 induction, and histology. In all these
      assays, the HVLV pulse combination gave rise to minimal disturbance of cell
      function, in all cases significantly different from results when using 8 HV
      pulses. The evaluated parameters were normalized after 1 week. The addition of
      DNA caused significantly more transmembrane exchange, and this may be due to
      entrance of the DNA through the membrane. In conclusion, this study
      comprehensively documents the immediate effects of DNA electrotransfer and shows
      that only slight cell disturbances occur with the HVLV pulses used for gene
      transfer. This is highly important, as minimal perturbation of cell physiology is
      essential for efficient transgene expression.

PMID- 19866490
TI  - Efficiency of high- and low-voltage pulse combinations for gene electrotransfer
      in muscle, liver, tumor, and skin.
AB  - Gene electrotransfer is gaining momentum as an efficient methodology for nonviral
      gene transfer. In skeletal muscle, data suggest that electric pulses play two
      roles: structurally permeabilizing the muscle fibers and electrophoretically
      supporting the migration of DNA toward or across the permeabilized membrane. To
      investigate this further, combinations of permeabilizing short high-voltage
      pulses (HV; hundreds of V/cm) and mainly electrophoretic long low-voltage pulses
      (LV; tens of V/cm) were investigated in muscle, liver, tumor, and skin in rodent
      models. The following observations were made: (1) Striking differences between
      the various tissues were found, likely related to cell size and tissue
      organization; (2) gene expression is increased, if there was a time interval
      between the HV pulse and the LV pulse; (3) the HV pulse was required for high
      electrotransfer to muscle, tumor, and skin, but not to liver; and (4) efficient
      gene electrotransfer was achieved with HV field strengths below the detectability
      thresholds for permeabilization; and (5) the lag time interval between the HV and
      LV pulses decreased sensitivity to the HV pulses, enabling a wider HV amplitude
      range. In conclusion, HV plus LV pulses represent an efficient and safe option
      for future clinical trials and we suggest recommendations for gene transfer to
      various types of tissues.

PMID- 19866488
TI  - Thermodynamic and structural insights into CSL-DNA complexes.
AB  - The Notch pathway is an intercellular signaling mechanism that plays important
      roles in cell fates decisions throughout the developing and adult organism.
      Extracellular complexation of Notch receptors with ligands ultimately results in
      changes in gene expression, which is regulated by the nuclear effector of the
      pathway, CSL (C-promoter binding factor 1 (CBF-1), suppressor of hairless
      (Su(H)), lin-12 and glp-1 (Lag-1)). CSL is a DNA binding protein that is involved
      in both repression and activation of transcription from genes that are responsive
      to Notch signaling. One well-characterized Notch target gene is hairy and
      enhancer of split-1 (HES-1), which is regulated by a promoter element consisting
      of two CSL binding sites oriented in a head-to-head arrangement. Although
      previous studies have identified in vivo and consensus binding sites for CSL, and
      crystal structures of these complexes have been determined, to date, a
      quantitative description of the energetics that underlie CSL-DNA binding is
      unknown. Here, we provide a thermodynamic and structural analysis of the
      interaction between CSL and the two individual sites that comprise the HES-1
      promoter element. Our comprehensive studies that analyze binding as a function of
      temperature, salt, and pH reveal moderate, but distinct, differences in the
      affinities of CSL for the two HES-1 binding sites. Similarly, our structural
      results indicate that overall CSL binds both DNA sites in a similar manner;
      however, minor changes are observed in both the conformation of CSL and DNA.
      Taken together, our results provide a quantitative and biophysical basis for
      understanding how CSL interacts with DNA sites in vivo.

PMID- 19866491
TI  - Hyperthermia-induced targeting of thermosensitive gene carriers to tumors.
AB  - Locoregional hyperthermia (HT) can be used for site-directed activation of
      macromolecular drug delivery systems. We have developed a gene delivery system
      based on thermosensitive block copolymers (TSCs) with a phase transition
      temperature of 42 degrees C [Zintchenko, A., Ogris, M., and Wagner, E. (2006).
      Bioconjug. Chem. 17, 766-772], in which the statistical copolymer of
      vinylpyrrolidinone and N-isopropylacryamide is grafted on polyethylenimine (PEI).
      Here we applied polyplexes consisting of plasmid DNA and TSCs systemically in A/J
      mice bearing a syngeneic Neuro2A neuroblastoma tumor subcutaneously in each hind
      limb. One limb was selectively treated by HT at 42 degrees C, at the same time
      that polyplexes were injected via the tail vein. Hyperthermia led to increased
      accumulation of thermosensitive polymer and aggregation of thermosensitive
      polyplexes in HT-treated tumors, resulting in up to 10-fold increased DNA
      deposition compared with non-HT-treated tumor. The level of transgene expression
      induced by TSC polyplexes in HT-treated tumors was significantly higher and
      selective for tumor tissue. With nonthermosensitive PEI polyplexes HT did not
      influence transgene deposition or expression in tumor.

PMID- 19866492
TI  - Differential transgene expression profiles in rat brain, using rAAV2/1 vectors
      with tetracycline-inducible and cytomegalovirus promoters.
AB  - The biodistribution of transgene expression in the CNS after localized
      stereotaxic vector delivery is an important issue for the safety of gene therapy
      for neurological diseases. The cellular specificity of transgene expression from
      rAAV2/1 vectors (recombinant adeno-associated viral vectors pseudotyped with
      viral capsids from serotype 1) using the tetracycline-inducible (TetON)
      expression cassette in comparison with the cytomegalovirus (CMV) promoter was
      investigated in the rat nigrostriatal pathway. After intrastriatal injection,
      although green fluorescent protein (GFP) was expressed mainly in neurons with
      both vectors, the relative proportions of DARPP-32-positive projection neurons
      and parvalbumin-positive interneurons were, respectively, 13:1 and 2:1 for the
      CMV and TetON vectors. DARP32-positive neurons projecting to the globus pallidus
      were strongly GFP positive with both vectors, whereas those projecting to the
      substantia nigra pars reticulata (SNpr) were efficiently labeled by the CMV
      vector but poorly by the TetON vector. Numerous GFP-positive cells were evidenced
      in the subventricular zone with both vectors. However, in the olfactory bulb
      (OB), GFP-positive neurons were observed with the CMV vector but not the TetON
      vector. We conclude that the absence of significant amounts of transgene product
      in distant regions (SN and OB) constitutes a safety advantage of the AAV2/1-TetON
      vector for striatal gene therapy. Midbrain injections resulted in selective GFP
      expression in tyrosine hydroxylase-positive neurons by the TetON vector whereas
      with the CMV vector, GFP-positive cells covered a widespread area of the
      midbrain. The biodistribution of GFP protein corresponded to that of the
      transcripts and not of the viral genomes. We conclude that the rAAV2/1-TetON
      vector constitutes an interesting tool for specific transgene expression in
      midbrain dopaminergic neurons.

PMID- 19866493
TI  - Neonatal intravenous injection of a gammaretroviral vector has a low incidence of
      tumor induction in mice.
AB  - Neonatal intravenous injection of gammaretroviral vectors (gamma-RVs) with an
      intact long terminal repeat (LTR) and an internal liver promoter can result in
      long-term expression in liver cells and correction of mucopolysaccharidosis. Some
      expression also occurs in blood cells and brain, which likely derives from the
      LTR, and may contribute to clinical efficacy. The goal of this project was to
      determine whether neonatal gene therapy with an LTR-intact gamma-RV would induce
      tumors in mice. Fifty-one normal newborn C57BL/6 mice were injected intravenously
      at 10(10) transducing units/kg with a gamma-RV expressing canine beta
      glucuronidase (GUSB) cDNA. This resulted in transduction of 23 +/- 9% of
      hepatocytes as determined by histochemical staining, and 0.24 +/- 0.20 copy of
      gamma-RV DNA per cell in liver as determined by real-time polymerase chain
      reaction. Serum GUSB activity was stable for 1.75 years after transduction at 705
      +/- 119 units/ml. Ninety-six percent of mice survived for the duration of
      evaluation, which was similar to the survival rate for 65 control mice that were
      not injected with gamma-RV. One gamma-RV-treated mouse (2%) developed a small
      (diameter, 2 mm) liver adenoma, which was similar to the frequency of liver
      adenomas (2%) or hepatocellular carcinoma (2%) in untreated mice. Although 22% of
      gamma-RV-treated mice developed hematopoietic tumors, none contained high gamma
      RV DNA copy numbers, and the frequency was similar to that in the control group
      (22%). We conclude that neonatal intravenous injection of an LTR-intact gamma-RV
      does not have a high risk of inducing cancer in mice.

PMID- 19866494
TI  - Journal Club: 35 years later, mRNA caps still matter.

PMID- 19866495
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Hospitalized patients with novel influenza A (H1N1) virus infection-
      California, April-May, 2009.

PMID- 19866496
TI  - Genetic matters of CYP2D6 in breast cancer: copy number variations and nucleotide
      polymorphisms.

PMID- 19866497
TI  - Carbon nanotubes: Not that slippery.

PMID- 19866498
TI  - [Treatment of incurable ill patients at intensive care units].

PMID- 19866499
TI  - [Dangerous adjuvant in swine influenza vaccine].

PMID- 19866500
TI  - [Misoprostol is not contraindicated in patients with asthma].

PMID- 19866501
TI  - [More about the right to acute death without resuscitation attempts].

PMID- 19866502
TI  - [Quick diagnosis guarantee--an absurd political move!].

PMID- 19866503
TI  - [What happened to the epicrisis from the out-of-hours care?].

PMID- 19866504
TI  - Patient flow variability and unplanned readmissions to an intensive care unit.
AB  - OBJECTIVE: To determine whether high patient inflow volumes to an intensive care
      unit are associated with unplanned readmissions to the unit. DESIGN:
      Retrospective comparative analysis. SETTING: The setting is a large urban
      tertiary care academic medical center. PATIENTS: Patients (n = 3233) discharged
      from an adult neurosciences critical care unit to a lower level of care from
      January 1, 2006 through November 30, 2007. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: The main outcome variable is unplanned patient readmission to the
      neurosciences critical care unit within 72 hrs of discharge to a lower level of
      care. The odds of one or more discharges becoming an unplanned readmission within
      72 hrs were nearly two and a half times higher on days when > or =9 patients were
      admitted to the neurosciences critical care unit (odds ratio, 2.43; 95%
      confidence interval, 1.39-4.26) compared with days with < or =8 admissions. The
      odds of readmission were nearly five times higher on days when > or =10 patients
      were admitted (odds ratio, 4.99; 95% confidence interval, 2.45-10.17) compared
      with days with < or =9 admissions. Adjusting for patient complexity, the odds of
      an unplanned readmission were 2.34 times higher for patients discharged to a
      lower level of care on days with > or =10 admissions to the neurosciences
      critical care unit (odds ratio, 2.34; 95% confidence interval, 1.27-4.34)
      compared with similar patients discharged on days of < or =9 admissions.
      CONCLUSIONS: Days of high patient inflow volumes to the unit were associated
      significantly with subsequent unplanned readmissions to the unit. Furthermore,
      the data indicate a possible dose-response relationship between intensive care
      unit inflow and patient outcomes. Further research is needed to understand how to
      defend against this risk for readmission.

PMID- 19866505
TI  - [Obesity related health care costs assessed from BMI or waist circumference-
      secondary publication].
AB  - Obesity is associated with increased risk of many diseases and mortality. The
      risk is related to body fat distribution such that abdominal obesity is
      associated with a greater risk than gluteo-femoral obesity. Individual cumulative
      health service costs were estimated in relation to waist circumference (WC) and
      body mass index (BMI). The analyses show that the combination of BMI and WC does
      not improve the identification of high-risk individuals compared with the use of
      WC alone. The health service costs increase by 1.24% in women and 2.08% in men
      pr. cm increase in WC above the normal range.

PMID- 19866506
TI  - Significance of arterial hypotension after resuscitation from cardiac arrest.
AB  - OBJECTIVE: Expert guidelines advocate hemodynamic optimization after return of
      spontaneous circulation (ROSC) from cardiac arrest despite a lack of empirical
      data on prevalence of post-ROSC hemodynamic abnormalities and their relationship
      with outcome. Our objective was to determine whether post-ROSC arterial
      hypotension predicts outcome among postcardiac arrest patients who survive to
      intensive care unit admission. DESIGN: Cohort study utilizing the Project IMPACT
      database (intensive care unit admissions from 120 U.S. hospitals) from 2001-2005.
      SETTING: One hundred twenty intensive care units. PATIENTS: Inclusion criteria
      were: 1) age > or =18 yrs; 2) nontrauma; and 3) received cardiopulmonary
      resuscitation before intensive care unit arrival. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Subjects were divided into two groups: 1)
      Hypotension Present--one or more documented systolic blood pressure <90 mm Hg
      within 1 hr of intensive care unit arrival; or 2) Hypotension Absent--all
      systolic blood pressure > or =90 mm Hg. The primary outcome was in-hospital
      mortality. The secondary outcome was functional status at hospital discharge
      among survivors. A total of 8736 subjects met the inclusion criteria. Overall
      mortality was 50%. Post-ROSC hypotension was present in 47% and was associated
      with significantly higher rates of mortality (65% vs. 37%) and diminished
      discharge functional status among survivors (49% vs. 38%), p < .001 for both. On
      multivariable analysis, post-ROSC hypotension had an odds ratio for death of 2.7
      (95% confidence interval, 2.5-3.0). CONCLUSIONS: Half of postcardiac arrest
      patients who survive to intensive care unit admission die in the hospital. Post
      ROSC hypotension is common, is a predictor of in-hospital death, and is
      associated with diminished functional status among survivors. These associations
      indicate that arterial hypotension after ROSC may represent a potentially
      treatable target to improve outcomes from cardiac arrest.

PMID- 19866507
TI  - Cardiac function index provided by transpulmonary thermodilution   behaves as an
      indicator of left ventricular systolic function.
AB  - OBJECTIVE: To test whether cardiac function index could actually behave as an
      indicator of left ventricular systolic function by testing if 1) it increased
      with inotropic stimulation; 2) it was not altered by fluid loading; 3) it
      correlated with the echographic left ventricular ejection fraction, considered as
      the clinical gold standard for measuring left ventricular systolic function, and
      it reliably tracked the changes in left ventricular ejection fraction during
      therapeutic intervention. The transpulmonary thermodilution calculates the
      cardiac function index, which is the ratio of cardiac output over global end
      diastolic volume. DESIGN: Prospective study. SETTING: Medical intensive care unit
      of a university hospital. PATIENTS: Thirty-nine patients (n = 48 cases) with
      acute circulatory failure. INTERVENTION: A 500-mL saline administration (n = 24
      cases) and a dobutamine infusion (n = 24 cases). MEASUREMENTS AND MAIN RESULTS:
      We simultaneously measured left ventricular ejection fraction (monoplane or
      biplane Simpson method) and cardiac function index at baseline and after saline
      and dobutamine administration. As volume expansion altered neither left
      ventricular ejection fraction (47 +/- 11% to 47 +/- 11%) nor cardiac function
      index (4.5 +/- 2.2 to 4.5 +/- 2.1 min(-1)), dobutamine infusion significantly
      increased left ventricular ejection fraction by 32 +/- 28% and cardiac function
      index by 29 +/- 22%. Considering the 96 cardiac function index:left ventricular
      ejection fraction pairs of measurements, cardiac function index and left
      ventricular ejection fraction were correlated significantly (r = .67, p < .05). A
      cardiac function index <3.2 min(-1) predicted a left ventricular ejection
      fraction of <35% with a sensitivity of 81% and a specificity of 88%. Importantly,
      the changes in left ventricular ejection fraction and in cardiac function index
      during fluid and dobutamine administration were correlated significantly (r =
      .79, p < .05). CONCLUSIONS: Cardiac function index fulfilled the criteria
      required from a clinical indicator of left ventricular global systolic function.
      Thus, it could serve as an easy bedside detection of the alteration in left
      ventricular ejection fraction that should alert the physician and incite to
      perform an echocardiography. Furthermore, cardiac function index tracked
      accurately the effects of an inotropic therapy.

PMID- 19866508
TI  - Selection of intensive care unit admission criteria for patients aged   80 years
      and over and compliance of emergency and intensive care   unit physicians with
      the selected criteria: An observational,   multicenter, prospective study.
AB  - OBJECTIVE: To describe intensive care unit referral decisions by emergency room
      physicians in patients aged > or =80 yrs. DESIGN: Prospective, observational
      cohort study of patients aged > or =80 yrs who were triaged in the emergency
      room, using a list of intensive care unit admission criteria selected by
      emergency physicians among 76 preliminary criteria adapted from the 1999 Society
      of Critical Care Medicine guidelines. The Delphi method was used to select the
      criteria. SETTING: Fifteen French hospitals. PATIENTS: A total of 2646 patients
      aged > or =80 yrs with at least one criterion. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: In the Delphi process, level of agreement was assessed as
      follows: when all answers fell within a single interval (7-9 = definite admission
      criteria; 4-6 = equivocal admission criteria or 1-3 = inappropriate admission),
      agreement was strong; when answers spanned two intervals, agreement was fair; and
      when answers spanned all three intervals, agreement was poor. Of the 76
      preliminary criteria, two were removed; 44 were selected as definite intensive
      care unit admission criteria; and 30 were selected as equivocal intensive care
      unit admission criteria. Of the 1426 patients meeting definite admission
      criteria, 441 (30.9%) were referred for intensive care unit admission and 231 of
      441 (52.4%) were admitted to the intensive care unit. Of the 1041 patients with
      equivocal admission criteria, 181 (17.3%) were referred for intensive care unit
      admission; and, of these, 79 (43.6%) were admitted to the intensive care unit.
      Factors associated independently with no intensive care unit referral were age
      odds ratio [OR], 1.04; 95% confidence interval [CI], 1.04-1.07), active cancer
      (OR, 1.61; 95% CI, 1.09-1.38), unknown hospitalization status (OR, 1.53; 95% CI,
      1.11-2.11), unknown living arrangements (OR, 1.69; 95% CI, 1.19-2.42), regular
      psychotropic medications (OR, 1.42; 95% CI, 1.10-1.81), low severity at referral
      (OR, 0.60; 95% CI, 0.53-0.68), low activity in daily living score (OR, 0.93; 95%
      CI, 0.88-0.99). CONCLUSIONS: Emergency and intensive care unit physicians were
      extremely reluctant to consider intensive care unit admission of patients aged >
      or =80 yrs, despite the presence of criteria indicating that intensive care unit
      admission was certainly or possibly appropriate.

PMID- 19866509
TI  - Bridging from medical informatics, biometry and epidemiology to medical
      engineering.

PMID- 19866510
TI  - [The health care debate in USA hits the core of the American self comprehension].

PMID- 19866511
TI  - [Danish guidelines for hematuria in children].

PMID- 19866512
TI  - [The Danish Medicines Agency should reconsider the criteria of generic
      substitution between fentanyl depot patches].

PMID- 19866513
TI  - [Patients safety work also for physicians].

PMID- 19866514
TI  - [Physicians' legal rights are weak].

PMID- 19866515
TI  - Retraction notice to "3D delineation of prostate, rectum and bladder on MR
      images" [Comput Med Imag Graph 32 (2008) 622-630].

PMID- 19866516
TI  - The Viracept-EMS case: impact and outlook.
AB  - This perspective first considers the potential impact of the Viracept-EMS case in
      the framework of the current understanding of the low-dose effects of DNA
      reactive chemicals and the approaches used to estimate health risks from
      genotoxins occurring as impurities in pharmaceutical products or as contaminants
      in the environment or workplace. It also presents an outlook on the nature of
      additional research building upon the Viracept-EMS case to test assumptions
      underlying thresholded dose-response relationships and to establish biologically
      based risk assessment models in lieu of default models for DNA-reactive
      compounds.

PMID- 19866517
TI  - European health systems face scrutiny in US debate.

PMID- 19866518
TI  - USA looks set to repeal HIV travel ban.

PMID- 19866519
TI  - Sex ratio imbalance worsens in Vietnam.

PMID- 19866520
TI  - The suffering of physicians.

PMID- 19866521
TI  - Editorial: Putting the yoke back in zygote.

PMID- 19866524
TI  - Be sure to get the results of your medical tests.

PMID- 19866522
TI  - Current trends in initial management of oropharyngeal cancer: the declining use
      of open surgery.
AB  - The widespread availability of novel primary treatment approaches against
      oropharyngeal cancers has provided several potentially curative surgical and
      nonsurgical treatment options for patients, generating both hope and controversy.
      As treatment is usually curative in intent, management considerations must
      include consideration of primary tumor and nodal disease control as well as long
      term toxicities and functional outcomes. Anatomical and functional organ
      preservation (speech and deglutition) remains of paramount importance to patients
      with oropharyngeal cancer and the physicians involved in their care, accounting
      for the growing popularity of chemoradiotherapy and transoral surgical techniques
      for this indication. These novel approaches have greatly diminished the role of
      open surgery as initial therapy for oropharyngeal cancers. Open surgery which is
      often reserved for salvage on relapse, may still be an appropriate therapy for
      certain early stage primary lesions. The growing treatment armamentarium requires
      careful consideration for optimal individualized care. The identification of
      oncogenic human papillomavirus as a predictive and prognostic marker in patients
      with oropharyngeal cancer has great potential to further optimize the choice of
      treatment. In this review, novel primary therapies against oropharyngeal squamous
      cell carcinoma are presented in the context of anatomical, quality of life, and
      emerging biological considerations.

PMID- 19866523
TI  - Intraoperative modification of a supracricoid laryngectomy to a subtotal
      laryngectomy with tracheohyoidoepiglottopexy.
AB  - In recent decades, with the widespread diffusion of the supracricoid laryngectomy
      in the treatment of selected advanced laryngeal neoplasm, the indications to non
      conservative surgery are less frequent than in past. We report the case of a
      patient in whom a planned supracricoid laryngectomy was intraoperatively
      converted in an extended partial laryngectomy with tracheohyoidoepiglottopexy for
      a tumor involving the cricoid cartilage.

PMID- 19866525
TI  - Barriers to employing young nurses in aged care.

PMID- 19866526
TI  - Enlightened experience in aged care.

PMID- 19866527
TI  - Disasters no excuse for euthanasia.

PMID- 19866528
TI  - Don't forget to polarize your lenses! Talc in the liver.

PMID- 19866529
TI  - Spasmodic dysphonia, perceptual and acoustic analysis: presenting new diagnostic
      tools.
AB  - In this article, we investigate whether (1) the IINFVo (Impression,
      Intelligibility, Noise, Fluency and Voicing) perceptual rating scale and (2) the
      AMPEX (Auditory Model Based Pitch Extractor) acoustical analysis are suitable for
      evaluating adductor spasmodic dysphonia (AdSD). Voice recordings of 12 patients
      were analysed. The inter-rater and intra-rater consistency showed highly
      significant correlations for the IINFVo rating scale, with the exception of the
      parameter Noise. AMPEX reliably analyses vowels (correlation between PUVF
      (percentage of frames with unreliable F0/voicing 0.748), running speech
      (correlation between PVF (percentage of voiced frames)/voicing 0.699) and
      syllables. Correlations between IINFVo and AMPEX range from 0.608 to 0.818,
      except for noise. This study indicates that IINFVo and AMPEX could be robust and
      complementary assessment tools for the evaluation of AdSD. Both the tools provide
      us with the valuable information about voice quality, stability of F0
      (fundamental frequency) and specific dimensions controlling the transitions
      between voiced and unvoiced segments.

PMID- 19866530
TI  - [Patient with primary pyelofibrosis--extramedullary hematopoiesis in the
      pelvicalyceal system and ureters].

PMID- 19866531
TI  - Hyperhidrosis in association with efavirenz.
AB  - Hyperhidrosis may be an adverse drug event (ADE) induced by the effect on any of
      the components of human thermoregulation. Some of our efavirenz (EFV)-treated
      patients have reported excessive nocturnal sweating that resolved after dose
      reduction. A representative clinical case of a male patient being treated with a
      night-time 600-mg dose of EFV who reported severe nocturnal sweating is reported
      here. His EFV plasma concentrations were always above normal and he was
      homozygous for a deficient function-allele of CYP2D6; for this reason, his EFV
      dose was reduced to 400mg=d. Simultaneous with this reduction, the patient
      described a progressive decrease in nocturnal sweating until its complete
      disappearance 15-20 days after this new drug dosage. The mechanism explaining
      sweating could be similar to the one suggested for hyperhidrosis related to
      serotonin uptake inhibitors, because this hyperhidrosis is episodic, nocturnal,
      and dose dependent. Hyperhidrosis could correspond to a dose-dependent ADE
      induced by EFV, therefore, a reduction of EFV from 600 to 400mg/d seems to
      control it. EFV crosses the hematoencephalic barrier and reaches a mean
      concentration in the cerebroespinal fluid equivalent to 0.69% of the plasma
      concentration. The ability of EFV to accessing the central nervous system (CNS)
      could explain an effect on thermoregulation. Hyperhydrosis is not easily
      discovered through a routine anamnesis because it is not noted on the EFV package
      insert, so its incidence may be higher than expected. Additionally, hyperhidrosis
      may be an indicator of elevated EFV plasma concentrations and hence may be
      controlled through a reduction of dose.

PMID- 19866533
TI  - Young people in the United Kingdom and Ireland with perinatally acquired HIV: the
      pediatric legacy for adult services.
AB  - Children with perinatally acquired HIV-1 infection are surviving into adolescence
      and increasingly transitioning toward adult services. Planning appropriate
      services in adult life requires an understanding of their progress through
      pediatric care. We describe the demographic features, disease progression,
      antiretroviral therapy (ART), and resistance in young people aged 10 years or
      more living in the United Kingdom and Ireland reported to the National Study of
      HIV in Pregnancy and Childhood (NSHPC) with prospective annual follow-up in the
      Collaborative HIV Paediatric Study (CHIPS) between 1996 and September 2007. Six
      hundred fifty-four perinatally infected young people were identified; 76% black
      African, 57% born abroad. Median age at presentation and duration of follow-up
      was 1 and 11 years, respectively, if born in the United Kingdom/Ireland, and 8
      and 5 years if born elsewhere. One hundred sixty-nine (26%) ever had an AIDS
      defining illness. Ten died during adolescence. At last follow-up, 64% were on
      ART, 18% off treatment having previously received ART and 18% were ART naive. Of
      518 who had received highly active antiretroviral therapy (HAART), 47% were
      triple class experienced. At last follow-up 77 (12%) had CD4 counts less than 200
      per microliter; of those on HAART, 78% had HIV-1 RNA </=400 copies per
      milliliter, median CD4 count 554 (interquartile range [IQR] 324-802). Among 166
      with resistance assays on HAART, 52% and 12% had dual- and triple-class HIV-1
      associated resistance mutations, respectively. One hundred three (16%) young
      people had transferred to adult services. Young adults with perinatally acquired
      HIV-1 infection require coordinated multidisciplinary transitional care services
      and careful long-term follow-up in adult life.

PMID- 19866534
TI  - Knowledge of the Centers for Disease Control and Prevention's 2006 routine HIV
      testing recommendations among New York City internal medicine residents.
AB  - In 2006, the Centers for Disease Control and Prevention (CDC) endorsed routine
      voluntary HIV testing in health care settings to identify the many HIV-infected
      but undiagnosed persons. Realizing this goal will require primary care providers
      including internal medicine physicians to order HIV tests routinely. In
      particular, urban internal medicine trainees who work in high HIV prevalence
      settings need to adopt this approach. We therefore examined the practice of
      routine HIV testing and to identify factors that correlate with offering HIV
      testing to this group. We conducted a self-administered electronic cross
      sectional survey of New York City's (NYC) internal medicine residents on HIV
      testing-related knowledge, attitudes, and behaviors with 29 close-ended
      questions. Fifteen of 42 NYC internal medicine residency programs participated in
      early 2007. Of 1175 residents, 450 (38.3%) responded. Most (63.9%) ordered
      approximately 10 HIV tests in the past 6 months; 32.6% were aware of the 2006
      guidelines; 35.8% utilized a routine testing approach. Respondents aware of
      current guidelines were more likely to practice routine testing (odds ratio [OR]
      3.7, 95% confidence interval [CI]: 2.4-5.6). Two common barriers to testing were
      procedural: time-consuming consent process (27.1%); difficulty locating consent
      forms (19.3%). Most (68.4%) respondents indicated that oral consent would
      facilitate more testing. Most NYC internal medicine residents are not routinely
      offering HIV tests as advised by the 2006 CDC HIV testing guidelines and continue
      to test patients according to perceived patient HIV risk. This is likely
      contributing to their low testing rates. Most identified institutional and policy
      barriers to routine testing. Efforts should be made to improve dissemination of
      guidelines and address institutional and policy barriers to allow more people to
      learn their HIV status.

PMID- 19866532
TI  - Plasma lipid profile in pregnant women with HIV receiving nevirapine.
AB  - Limited information is currently available on the metabolic profile of nevirapine
      in pregnancy. We used data from a national observational study to evaluate plasma
      lipid profile in pregnant women receiving nevirapine. Lipid values were collected
      during routine clinical visits. Midpregnancy (second trimester) lipid values were
      analyzed according to use of nevirapine, calculating differences and 95%
      confidence intervals (CI) between women taking and not taking this drug. In order
      to adjust for possible confounders, multivariable models were constructed using
      as dependent variables levels of total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride
      (TG) levels and TC/HDL-C ratio, and as independent variables age, body weight,
      previous treatment history, CD4 count, and presence of any antiretroviral
      therapy, use or nonuse of protease inhibitors, stavudine, and nevirapine at the
      time of blood sampling. Overall, 375 women had available data for analysis.
      Pregnant women on nevirapine, compared to women not taking this drug, had in
      univariate analyses higher levels of HDL-C (difference: +13.0mg/dL [95%CI 7.4
      18.6], p < 0.001), lower values of TC/HDL-C ratio (difference: -0.51 [0.23-0.80],
      p < 0.001) and a trend for lower levels of triglycerides (difference: -17.6mg/dL
      [0.7-35.9], p = 0.06). Higher HDL-C levels were also associated with use of
      protease inhibitors and with no previous antiretroviral experience before
      pregnancy. The associations with higher HDL-C levels were confirmed in
      multivariable analyses. Our study indicates in pregnant women an association
      between nevirapine use and higher HDL-C levels. Further studies should assess
      whether this effect is due to an intrinsic activity of nevirapine and define the
      potential mechanisms involved.

PMID- 19866535
TI  - Development and efficacy of an intervention to enhance readiness for adherence
      among adults who had previously failed HIV treatment.
AB  - This paper outlines the development and initial testing of the READY intervention
      that was designed to enhance readiness for adherence among adults with a history
      of nonadherence to HIV treatment. Participants in this study were adults (n = 28)
      who ranged in age from 24 to 57: most were male (75%) and African American (64%).
      Participants had failed an average of four prior HIV treatment regimens due to
      nonadherence and were beginning a new regimen of protease inhibitor (PI)-based
      antiretroviral medications. The study was conducted from 2003 to 2006, prior to
      the standard use of boosted PI regimens. Results indicated that 50% of
      participants became adherent and had suppressed viral loads to less than 50
      copies per milliliter at the 3-month postintervention follow-up time point. Of
      those who became adherent, 79% remained adherent at the 12-month postintervention
      follow-up time point. Implementation of the intervention was found to be feasible
      in a real-world setting and participants reported that they liked the
      intervention. A 6-session length of the intervention was found to have the same
      impact on adherence outcomes as a 12-session length. No differences were found in
      outcomes with regard to the intervention's start time: before or at the same time
      the new antiretroviral regimen was initiated. These results suggest that the
      READY intervention may have merit and that the 6-session length may be more
      acceptable. However, a larger controlled study is indicated to examine
      intervention efficacy further.

PMID- 19866537
TI  - The changing face of the HIV epidemic in Taiwan: a new challenge for public
      health policy strategies.
AB  - The goals of this study were to examine trends, risk factors, and survival rates
      of people diagnosed with HIV/AIDS. We used national surveillance data reported to
      the Taiwan Center for Disease Control (Taiwan CDC). The subjects of this study
      were all confirmed HIV and AIDS cases in Taiwan. From 1990 through 2005, the
      number of people that have been reported to have HIV/AIDS is 9961. Among
      individuals with HIV/AIDS, the male-to-female ratio was 11:1, the median age was
      32 years. The number of HIV and AIDS diagnoses increased significantly for both
      men and women during the study period. The number of HIV cases among men who have
      sex with men (MSM) increased from 24 in 1990 to 527 in 2005, while diagnoses
      among injection drug users (IDUs) rose rapidly from 3 in 1990 to 2450 in 2005.
      The incidence-to-prevalence ratio (IPR) has risen sharply in recent years and has
      exceeded the epidemic threshold (IPR(t) = 0.1) for IDUs, indicating a growing
      epidemic. The corresponding hazard ratios for the highly active antiretroviral
      therapy (HAART) era versus pre-HAART era in the earlier and late HIV diagnosis
      groups were 0.45 (95% confidence interval [CI] 0.36-0.54) and 0.39 (95% CI 0.31
      0.49), respectively. There was no significant difference in the survival rate of
      HIV testers. The increasing number of HIV infection places Taiwan among the worst
      IDU-concentrated epidemic areas in Asia. HIV intervention and prevention
      strategies, especially targeting IDUs, are urgently needed to reduce the ongoing
      spread of HIV infections in Taiwan.

PMID- 19866536
TI  - Patient-related risks for nonadherence to antiretroviral therapy among HIV
      infected youth in the United States: a study of prevalence and interactions.
AB  - Adherence continues to be a major barrier to successful treatment with highly
      active antiretroviral therapy (HAART) for HIV-infected individuals. HIV-infected
      adolescents and young adults face a lifetime of treatment with HAART. Often,
      individuals who struggle with adherence to HAART face multiple barriers that
      would therefore impact on the success of any single modality intervention. Thus,
      we conducted a cross-sectional, observational study to determine the prevalence
      of personal barriers to adherence and to identify associations between these
      barriers in HIV-infected subjects, 12 to 24. We studied the following personal
      barriers to adherence: mental health barriers, high/low self-efficacy and outcome
      expectancy, and the presence of specific structural barriers. There were 396
      subjects infected after age 9 recruited from sites from the Adolescent Trials
      Network for HIV/AIDS Interventions or the Pediatric AIDS Clinical Trials Group.
      Of the 396 subjects, 148 (37.4%) self-identified as nonadherent. No significant
      differences were found between adherent and nonadherent subjects for the presence
      of mental health disorders. Adherence was significantly associated with all but
      one structural barrier. Both self-efficacy and outcome expectancy were higher
      among adherent versus nonadherent subjects (p < 0.0001). Grouping subjects
      according to low self-efficacy and outcome expectancy for adherence, adherence
      differed according to the presence or absence of mental health disorders and
      structural barriers (p < 0.0001). Our data suggest that adolescents have
      significant rates of non-adherence and face multiple personal barriers. Adherence
      interventions must address multiple barriers to have the maximum chance for
      positive effects.

PMID- 19866538
TI  - Barriers to sustaining antiretroviral treatment in Kisesa, Tanzania: a follow-up
      study to understand attrition from the antiretroviral program.
AB  - Two years after the introduction of free antiretroviral therapy (ART) in Tanzania
      and in spite of the logistical support provided to facilitate clinic attendance,
      a considerable level of attrition from the program was identified among clients
      from a semi-rural ward. Qualitative research on ART patients' health-seeking
      behavior identified factors affecting sustained attendance at treatment clinics.
      A mix of methods was used for data collection including semi-structured
      interviews with 42 clients and 11 service providers and 4 participatory group
      activities conducted with members of a post-test group between October and
      December 2006. A socio-ecological framework guided data analysis to categorize
      facilitators and barriers into individual, social, programmatic, and structural
      level influences, and subsequently explored their interaction and relative
      significance in shaping ART clients' behavior. Our findings suggest that personal
      motivation and self-efficacy contribute to program retention, and are affected by
      other individual-level experiences such as perceived health benefits or disease
      severity. However, these determinants are influenced by others' opinions and
      beliefs in the community, and constrained by programmatic and structural
      barriers. Individuals can develop the requisite willingness to sustain strict
      treatment requirements in a challenging context, but are more likely to do so
      within supportive family and community environments. Effectiveness and
      sustainability of ART roll-out could be strengthened by strategic intervention at
      different levels, with particular attention to community-level factors such as
      social networks' influence and support.

PMID- 19866539
TI  - HIV care providers' implementation of routine alcohol reduction support for their
      patients.
AB  - Screening and brief intervention (SBI) for alcohol reduction is an important
      health promoting strategy for patients with HIV, and HIV care providers are
      optimally situated to support their patients' reduction efforts. We report
      results from analyses that use data collected from providers (n = 115) in 7
      hospital-based HIV care centers in the New York City metropolitan area in 2007
      concerning their routine use of 11 alcohol SBI components with their patients.
      Providers routinely implemented 5 or more of these alcohol SBI components if they
      (1) had a specific caseload (and were therefore responsible for a smaller number
      of patients), (2) had greater exposure to information about alcohol's effect on
      HIV, (3) had been in their present positions for at least 1 year, and (4) had
      greater self efficacy to support patients' alcohol reduction efforts. Findings
      suggest the importance of educating all HIV care providers about both the
      negative impact of excessive alcohol use on patients with HIV and the importance
      and value of alcohol SBIs. Findings also suggest the value of promoting increased
      self efficacy for at least some providers in implementing alcohol SBI components,
      especially through targeted alcohol SBI training.

PMID- 19866540
TI  - Diversity of HIV strains impacts diagnostic test accuracy.

PMID- 19866541
TI  - Data demonstrate pharmacokinetic boosting activity of GS 9350.

PMID- 19866542
TI  - Radioimmunotherapy hold promise to treat HIV.

PMID- 19866543
TI  - IL-2 immunotherapy does not benefit patients taking antiretrovirals.

PMID- 19866544
TI  - Phase 1 trial starts for HCV protease inhibitor.

PMID- 19866546
TI  - Papers presented at Joint Meeting of the Section on Urology, American Academy of
      Pediatrics and International Children's Continence Society, Joint Meeting of the
      Section on Urology, American Academy of Pediatrics and International Children's
      Continence Society, Boston, Massachusetts, USA, 10-13 October 2008.

PMID- 19866545
TI  - No fruit fly an island?

PMID- 19866547
TI  - Prescription standards are necessary to improve health literacy and medication
      safety.

PMID- 19866548
TI  - Malaria's primate links.

PMID- 19866550
TI  - 2009 Community Leadership Awards: Georgia hospitals recognized for community
      work.

PMID- 19866549
TI  - Masks might limit spread of swine flu.

PMID- 19866551
TI  - Health care reform update.

PMID- 19866552
TI  - [Prophylactic medication guidelines for relevant personnel in close contacts with
      H1N1 type A influenza (interim 2009 edition)].

PMID- 19866553
TI  - ULTRASTRUCTURE OF THE LAMELLAE AND GRANA IN THE CHLOROPLASTS OF ZEA MAYS L.
AB  - The fine structure of the chloroplasts of maize (Zea mays L.) has been
      investigated by electron microscopic examination of ultrathin sections of leaves
      fixed in buffered osmium tetroxide solutions. Both the parenchyma sheath and
      mesophyll chloroplasts contain a system of densely staining lamellae about 125 A
      thick immersed in a finely granular matrix material (the stroma), and are bounded
      by a thin limiting membrane which often appears as a double structure. In the
      parenchyma sheath chloroplasts, the lamellae usually extend the full width of the
      disc-shaped plastids, and grana are absent. The mesophyll chloroplasts, however,
      contain numerous grana of a fairly regular cylindrical form. These consist of
      highly ordered stacks of dense lamellae, the interlamellar spacing being ca. 125
      A. The grana are interlinked by a system of lamellae (intergrana lamellae) which
      are on the average about one-half as numerous as the lamellae within the grana.
      In general, this appears to be due to a bifurcation of the lamellae at the
      periphery of the granum, but more complex interrelationships have been observed.
      The lamellae of the parenchyma sheath chloroplasts and those of both the grana
      and intergrana regions of the mesophyll chloroplasts exhibit a compound structure
      when oriented normally to the plane of the section. A central exceptionally dense
      line (ca. 35 A thick) designated the P zone is interposed between two less dense
      layers (the L zones, ca. 45 A thick), the outer borders of which are defined by
      thin dense lines (the C zones). Within the grana, the C zones, by virtue of their
      close apposition, give rise to thin dense intermediate lines (I zones) situated
      midway between adjacent P zones. A model of the lamellar structure is proposed in
      which mixed lipide layers (L zones) are linked to a protein layer (P zone) by non
      polar interaction. Chlorophyll is distributed over the entire lamellar surface
      and held in the structure by van der Waals interaction of the phytol "tail" with
      the hydrocarbon moieties of the mixed lipide layers. The evidence in favour of
      the model is briefly discussed.

PMID- 19866555
TI  - A SUGGESTION AS TO THE NATURE OF THE LYSOSOME GRANULES.

PMID- 19866554
TI  - STRUCTURE AND DEVELOPMENT OF VIRUSES OBSERVED IN THE ELECTRON MICROSCOPE : IV.
      VIRUSES OF THE RI-APC GROUP.
AB  - Representative viruses of the RI-APC group were observed with the electron
      microscope in thin sections of infected HeLa cells. The viral particles varied in
      density, were approximately 60 mmicro in diameter and had a center to center
      spacing when close packed of about 65 mmicro. Many of the less dense particles
      exhibited an internal body averaging 24 mmicro in diameter. It was suggested that
      within the nucleus the virus differentiated from dense granular and reticular
      material and formed crystals. Disintegration of the crystals and disruption of
      the nuclear membrane with release of virus into the cytoplasm appeared to occur
      at any stage. No evidence to suggest development of the virus in the cytoplasm
      was obtained. It was possible to deduce the structure of the viral crystal from
      the electron micrographs. The viral particles are packed in a cubic body-centered
      lattice. Correlative histochemical observations in the light microscope which are
      now in progress revealed that the crystals and non-crystalline aggregates of
      virus were strongly Feulgen-positive.

PMID- 19866556
TI  - THE FORMATION OF MYELIN IN THE PERIPHERAL NERVES OF VERTEBRATES.

PMID- 19866557
TI  - APPLICATIONS OF A DIAMOND KNIFE FOR ULTRATHIN SECTIONING TO THE STUDY OF THE FINE
      STRUCTURE OF BIOLOGICAL TISSUES AND METALS.

PMID- 19866558
TI  - THE FORM BIREFRINGENCE OF LAMELLAR SYSTEMS CONTAINING THREE OR MORE COMPONENTS.
AB  - Equations are derived which predict the form birefringence of lamellar systems
      containing three or more components. These equations may be found useful in
      interpreting the birefringence of biological specimens and in testing certain
      theories about the structure of natural membranes.

PMID- 19866559
TI  - Permeability and Structural Characteristics of Isolated Nuclei from Chaetopterus
      Eggs.
AB  - The germinal vesicle of the mature Chaetopterus egg is invested by an envelope
      which can be seen in electron micrographs to contain "pores" in its bilaminar
      structure. While under continuous microscopic observation, individual germinal
      vesicles were isolated in various test solutions by an extremely gentle method.
      Repeated measurements of nuclear diameter and of optical path differences with an
      interference microscope provided data on changes in mass after isolation. It was
      found that bovine serum albumin can readily penetrate the nuclear envelope of the
      isolated nucleus and that there are soluble elements which rapidly diffuse out. A
      relatively non-diffusible mass is lost at a much slower rate, the proportion of
      soluble to non-diffusible mass being dependent on the ionic environment. Calcium
      and manganese increase the proportion of the non-diffusible mass at the expense
      of the soluble components, while potassium decreases it. The shape and size of
      the isolated nucleus is at least partially dependent on the non-diffusible mass
      of its interior. Digestion with trypsin causes a complete structural collapse and
      loss of the non-diffusible elements, along with disappearance of the nucleolus.
      The nucleus shrinks and becomes wrinkled. A small residual mass is left which is
      probably associated with the nuclear envelope. Digestion with RNase or DNase
      causes no detectable effect on the isolated nucleus. Micromanipulation of the
      isolated nucleus consistently indicates that there are strands emanating from the
      nucleus. They may be up to several hundred microns long, are structurally strong,
      and are not destroyed by trypsin, RNase, or DNase. Electron micrographs of thin
      sections of intact cells show that the germinal vesicle is highly irregular in
      outline with complex evaginations extending into the cytoplasm. With the light
      microscope the isolated nucleus looks spherical and smooth and no emanating
      strands can be seen. The nature of the strands is not known.

PMID- 19866560
TI  - Electron Microscopic Observations of Rabbit Antibodies.
AB  - Electron micrographs were obtained showing the individual, shadow-cast
      macromolecules from solutions of purified anti-p-azobenzoate rabbit antibody and
      of normal gamma-globulin. The two materials look alike and consist mainly of
      asymmetrical rod-like particles about 30 to 40 A in diameter. Lengths are not
      constant but the weight average is about 250 A for the antibodies and about 200 A
      for the gamma-globulin. The average observed dimensions are reasonably consistent
      with values deduced from physical-chemical methods, although the shape is more
      nearly that of a cylindrical rod rather than the ellipsoid employed in
      hydrodynamical theory. Mixtures of antibody and specific dihaptenic dye were
      examined in attempts to establish the mode of the specific aggregation. At the
      high dilutions necessary for electron microscopy (0.1 mg./ml.), the effect of the
      dye was small and tended to be masked by non-specific aggregation on drying. The
      evidence suggests that under these conditions the specific reaction involves an
      end-to-end aggregation of the elementary particles to produce a weight average
      length about twice that of the pure antibody.

PMID- 19866561
TI  - Chemical and Morphological Studies of Bacterial Spore Formation : I. The
      Formation of Spores in Bacillus cereus.
AB  - Experimental conditions were developed whereby a culture of Bacillus cereus
      formed spores with reasonable synchrony following a growth cycle of some 8 hours.
      The cytology of this metamorphosis was studied by dark phase contrast, bright
      field microscopy and electron microscopy of thin sections. Particular attention
      has been paid to the changes in chromatin patterns and these have been correlated
      with quantitative chemical estimations of the nucleic acids. The cell commencing
      sporulation contains two compact chromatin bodies and twice the spore amount of
      deoxyribonucleic acid. Following fusion of the two chromatin bodies, one-half of
      this chromatin becomes located at a cell end. A transverse septum growing inwards
      from, and remaining attached to, the inner surface of the cell wall separates
      this end-piece of chromatin and some associated cytoplasm from the rest of the
      cell to form the primordial spore. Although the synthesis of deoxyribonucleic
      acid ceases during the segregation process, it recommences in this organism and
      continues at a linear rate as the spore develops. Tracer studies with radioactive
      phosphorus indicated that this further synthesis is confined to the non-spore
      portion of the sporangium. Although the net synthesis of ribonucleic acid ceased
      prior to the onset of sporogenesis, some evidence of a turnover of this fraction
      during the sporulation process was found.

PMID- 19866562
TI  - Internal Structure of Apoferritin as Revealed by the "Negative Staining
      Technique.".

PMID- 19866563
TI  - The Multiplicity of the Mitotic Centers and the Time-Course of Their Duplication
      and Separation.
AB  - In this study, the reproduction of the mitotic centers in the eggs of a sea
      urchin, Strongylocentrotus purpuratus and a sand dollar Dendraster excentricus
      has been studied by means of experimental designs that do not depend on the
      actual visualization of centrioles. The centers are defined in operational terms
      as potential poles. Blockage of mitosis by mercaptoethanol, it was found,
      inhibits the duplication of the centers, but does not inhibit the splitting and
      separation of centers that have already duplicated and thus potential poles could
      be realized as actual poles in multipolar divisions. At all times, the center is
      at least a duplex structure; that is, it contains two potential poles. The actual
      duplication process is the earliest event in a given mitotic cycle, taking place
      at very early interphase or in late telophase of the previous division. The
      splitting of the centers following duplication is a distinct process, dissociable
      from the duplication as such. Duplication and splitting normally occur at about
      the same time in the mitotic cycle, with a precession of the former. That is, as
      the two members of a pair of "old" centers split, each one gives rise to a new
      one, which remains associated with it until the next phase of splitting and
      duplication occurs. The results are consistent with what is termed a "generative"
      model of the self-reproduction of an intracellular body. According to this, the
      body does not immediately produce a full-fledged copy of itself, with
      simultaneous fission, but the primary duplication event involves only a part of
      the parent structure. This gives rise to a "germ" or "seed" which then grows to
      be equivalent to the parent body, and finally splits from it.

PMID- 19866564
TI  - The Relative Concentration of Solids in the Nucleolus, Nucleus, and Cytoplasm of
      the Developing Nerve Cell of the Chick.
AB  - Growing and differentiating nerve cells of the fifth cranial ganglion of the
      chick embryo were studied by several means. During the period of 70 hours to 11
      days of incubation (Hamburger-Hamilton stages 19 to 37) average cell mass
      increased more than 4.5 times while cells changed from relatively
      undifferentiated neuroblasts to morphologically characteristic nerve cells with
      long processes. By making simplifying assumptions about thickness of nucleus and
      nucleolus, relative to cytoplasmic thickness, it was possible to calculate solute
      concentration of nucleus and nucleolus relative to that of the cytoplasm from
      measurements of optical retardations through living cells. Differences in
      relative solute concentration were observed in nucleolus, cytoplasm, and
      nucleoplasm in the approximate ratio 1.2:1.0:0.8, respectively. The ratio
      remained essentially constant during the growth period examined despite the fact
      that the cell components grow at markedly different rates. This suggests that
      solid concentrations are physical characteristics of nucleus, nucleolus, and
      cytoplasm which are maintained even during rapid growth and differentiation. By
      cytochemical means it was demonstrated that mass increase in the nucleus is not
      associated with increase in deoxyribonucleic acid. Both ribonucleic acid and
      protein are in greater concentration in nucleolus and cytoplasm than in the
      nucleoplasm. Electron microscopy shows interruptions in the nuclear envelope as
      well as an approximately even distribution of electron density in nucleus and
      cytoplasm. It is pointed out that consistent differences in solid concentration
      can exist on either side of the nuclear envelope even though it contains "pores."
      Implications of these data are discussed.

PMID- 19866565
TI  - Monochromatic Ultraviolet Microscopy of Microorganisms: Preliminary Observations
      on Bacterial Spores.

PMID- 19866566
TI  - Electron Microscopy of the Degeneration of Fine Structure in Saintpaulia ionantha
      Wendl. Pollen Walls.

PMID- 19866567
TI  - Electron Microscopy of Solitary and Aggregated Slime Mould Cells.
AB  - Polysphondylium violaceum and Dictyostelium discoideum myxamoebae have simple
      double-layered nuclear membranes, a cytoplasmic reticulum of particle-covered
      membranes, and small mitochondria consisting of convoluted tubules tightly packed
      in double membranes. In addition to objects still recognisable as bacteria, their
      food vacuoles contain concentric (or spiral) membranes, apparently formed
      secondarily from undigested material; these are ultimately ejected. Where the
      triple-layered plasma membranes ( approximately 70 A wide) of cells in the early
      aggregates are apposed to one another, they run parallel but separated by a layer
      of rather constant thickness ( approximately 200 A), as in many unspecialised
      metazoan tissues. Thus studies on slime moulds may well increase our
      understanding of cell adhesion and tissue formation in metazoa.

PMID- 19866568
TI  - CELLULAR SPECIALIZATION IN THE EXCRETORY EPITHELIA OF AN INSECT, Macrosteles
      fascifrons STAL (HOMOPTERA).
AB  - An electron microscopic investigation of the Malpighian tubules of a leaf hopper,
      Macrosteles fascifrons, shows that these organs comprise three quite distinct
      cell types, and the structure of these and of the mid- and hindgut epithelial
      cells is described. In particular, a comparison is made between the organization
      of the basal and apical surfaces of cells in the Malpighian tubule and in the
      vertebrate kidney, and it is suggested that similarities between these excretory
      epithelia reflect functional parallels between them. While the midgut and one
      region of the Malpighian tubule bear a typical microvillar brush border,
      elsewhere in the tubule and in the hindgut the apical surface bears cytoplasmic
      leaflets or lamellae. The sole solid excretory material of these insects consists
      of the brochosomes, secreted by cells of one region of the Malpighian tubule. The
      structure, geometry, and development of these unusual bodies, apparently formed
      within specialized Golgi regions, has been investigated, and histochemical tests
      indicate that they contain lipid and protein components.

PMID- 19866569
TI  - STUDIES ON CARTILAGE : II. Electron Microscope Observations on Rabbit Ear
      Cartilage following the Administration of Papain.
AB  - Electron microscope observations on rabbit ear cartilage following the
      administration of papain show that both the elastic component of the matrix and
      the amorphous material disappear leaving a matrix which consists of delicate
      fibrils which are presumed to be collagen. This unmasking of fibrils coincides
      with the appearance of an abnormal component in the electrophoretic pattern of
      the rabbit's serum. The chondrocytes show vacuoles in their cytoplasm which
      appear at the same time that the cells appear crenated in the light microscope. A
      ruffly appearance of the cell surface membrane coincides with this vacuolization,
      and vacuoles often appear open and in continuity with the extracellular space.
      The resurgence of the rabbit ear is accompanied by a reconstitution of both the
      amorphous material and the elastic component of the matrix. During this period
      numerous dilated cisternae of the endoplasmic reticulum which contain a
      moderately dense material are present in the chondrocyte cytoplasm. We have been
      unable to demonstrate a direct relationship between the elastic component of the
      matrix and a particular component of the chondrocyte cytoplasm, but it is clear
      that changes occur in the cartilage cell cytoplasm during both the depletion and
      reconstitution of the matrix. Previous studies on the effect of papain on elastic
      tissue are noted and the possible relationships between changes in the cells and
      matrix of this elastic cartilage are discussed.

PMID- 19866570
TI  - CHANGES IN NUCLEAR HISTONES DURING FERTILIZATION, AND EARLY EMBRYONIC DEVELOPMENT
      IN THE PULMONATE SNAIL, Helix aspersa.
AB  - Calf thymus histories comprising two fractions, one rich in lysine, the other
      having roughly equal amounts of lysine and arginine, Loligo testes histones rich
      in arginine, and salmine, are compared with respect to their amino acid
      compositions, and their staining properties when the proteins are fixed on filter
      paper. The three types of basic proteins; somatic, arginine-rich spermatid
      histones, and protamine can be distinguished on the following basis. Somatic and
      testicular histones stain with fast green or bromphenol blue under the same
      conditions used for specific staining of histones in tissue preparations. The
      former histones lose most or all of their stainability after deamination or
      acetylation. Staining of the arginine-rich testicular histones remains relatively
      unaffected by this treatment. Protamines do not stain with fast green after
      treatment with hot trichloracetic acid, but are stained by bromphenol blue or
      eosin after treatment with picric acid. These methods provide a means for the
      characterization of nuclear basic proteins in situ. Their application to the
      early developmental stages of Helix aspersa show the following: After
      fertilization the protamine of the sperm is lost, and is replaced by faintly
      basic histones which differ from adult histones in their inability to bind fast
      green, and from protamines, by both their inability to bind eosin, and their
      weakly positive reaction with bromphenol blue. These "cleavage" histones are
      found in the male and female pronuclei, the early polar body chromosomes, and the
      nuclei of the cleaving egg and morula stages. During gastrulation, the histone
      complement reverts to a type as yet indistinguishable from that of adult somatic
      cells.

PMID- 19866571
TI  - INNERVATION OF THE FIBRILLAR FLIGHT MUSCLE OF AN INSECT: TENEBRIO MOLITOR
      (COLEOPTERA).
AB  - The structure of peripheral nerves, and the organization of the myoneural
      junctions in flight muscle fibers of a beetle is described. The uniaxonal
      presynaptic nerve branches display the "tunicated" structure reported in the case
      of other insect nerves and the relationship between the axon and the lemnoblast
      folds is discussed. The synapsing nerve terminal shows many similarities with
      that of central and peripheral junctions of other insects and of vertebrates
      (e.g., the intra-axonal synaptic vesicles) but certain important differences have
      been noted between this region in Tenebrio flight muscle and in other insect
      muscles. Firstly, the axon discards the lemnoblast before the junction is
      established and the axon effects a circumferential synapse with the plasma
      membrane of the fiber, which alone shows the increased thickness often observed
      in both pre- and postsynaptic elements. Secondly, in addition to the synaptic
      vesicles within the axon are present, in the immediately adjacent sarcoplasm,
      great numbers of larger postsynaptic vesicles which, it is tentatively suggested,
      may represent the sites of storage of the enzymatic destroyer of the activating
      substance similarly quantized within the intra-axonal vesicles. The spatial
      relationship between the peripherally located junctions and the portion of the
      fiber plasma membrane internalized as circumtracheolar sheaths is considered, and
      the possible significance of this with respect to impulse conduction is discussed
      briefly.

PMID- 19866572
TI  - MITOCHONDRIA ASSOCIATED WITH THE KINETONUCLEUS OF TRYPANOSOMA MEGA.

PMID- 19866573
TI  - THE EXISTENCE OF A CYTOSTOME AND THE OCCURRENCE OF PINOCYTOSIS IN THE
      TRYPANOSOME, TRYPANOSOMA MEGA.

PMID- 19866574
TI  - THE STAINING OF THIN SECTIONS OF MOUSE PANCREAS PREPARED BY THE FERNANDEZ-MORAN
      HELIUM II FREEZE-SUBSTITUTION METHOD.
AB  - Small pieces of mouse pancreas were rapidly frozen in helium II, substituted in
      methanol at -75 degrees C., and embedded in methacrylate by ultraviolet
      polymerization in the cold. The unstained cells show a structure similar to that
      after OsO(4) fixation, except that the RNP particles have little or no contrast
      and the mitochondria and Golgi zones appear as grey areas without internal
      structure. After staining the sections by floating them on solutions of lead
      acetate or osmium tetroxide, there is an increase in contrast of RNP particles,
      ergastoplasmic membranes, and zymogen granules. Mitochondrial and Golgi
      membranes, zymogen granule membranes, and a membrane along the outside of the
      ergastoplasmic cisterna appear in negative contrast. The structure of the
      ergastoplasm, the existence of RNP particles, and the production of negative
      contrast are discussed. A modification of Gomori's method for acid phosphatase
      produces a lead deposit around the periphery of the zymogen granules. Possibly
      this deposit does not represent the true site of the enzyme, but the results show
      the feasibility of histochemistry at the level of resolution of the electron
      microscope.

PMID- 19866575
TI  - AN ELECTRON MICROSCOPIC STUDY OF PINOCYTOSIS IN AMEBA : I. The Surface Attachment
      Phase.
AB  - The attachment to the surface of the ameba (Chaos chaos L. (Pelomyxa
      carolinensis, Wilson)) of two proteins, ribonuclease and ferritin, and two
      colloidal suspensions, thorium dioxide and gold, was studied in the electron
      microscope. The initial step in the pinocytosis of ferritin and thorium dioxide
      particles by amebas is shown to be the attachment of these substances to the
      "hairlike" extensions of the plasmalemma. Ribonuclease caused alterations in the
      structure of the plasmalemma, but on account of its relative lack of density, it
      could not be definitely localized. Colloidal gold did not appear to be active
      with respect to pinocytosis in amebas. Since molecules in solution and particles
      in suspension are taken up by the same mechanism, the first step of which is
      their attachment to the cell surface, it is suggested that a single mechanism
      underlies phagocytosis, pinocytosis, ropheocytosis, cytopempsis, and potocytosis.

PMID- 19866576
TI  - IRRADIATION ULTRA-VIOLETTE DES ORGANITES CELLULAIRES AVEC OBSERVATION CONTINUE EN
      CONTRASTE DE PHASE.
AB  - The apparatus described is designed to permit the observation of the smallest
      cellular components with the phase contrast microscope (which requires an
      objective of a high numerical aperture) while a part of the cell is irradiated by
      a very small spot of ultraviolet radiation. Theoretical considerations show a
      good distribution of the energy for a diameter of the irradiation spot as small
      as 0.2 microns. Indications are given about the limitations of the brightness
      caused by diffraction at the spot diaphragm and the energy absorption by volume
      unit of the irradiated object. The practical applications of the apparatus are
      discussed.

PMID- 19866577
TI  - THE SOURCE OF LIPID ACCUMULATION IN L CELLS.
AB  - Strain L cells accumulate lipid, concurrent with cessation of protein synthesis,
      in the stationary phase of growth from the extracellular medium and as a result
      of de novo synthesis. Cells which have been more severely damaged with an amino
      acid analogue also accumulate lipid from the extracellular medium, but synthesize
      very little lipid from labeled acetate. The possible roles which lipid
      accumulation may play in the cell are discussed.

PMID- 19866578
TI  - THE FINE STRUCTURE OF HAEMATOLOECHUS SPERMATOZOAN TAIL.

PMID- 19866579
TI  - A STUDY OF THE PENETRATION OF MAMMALIAN CELLS BY DEOXYRIBONUCLEIC ACIDS.
AB  - Tritium-labeled deoxyribonucleic acid (DNA) from pneumococci and from human
      leukocytes was added to growing cultures of HeLa cells at 37 degrees C.
      Autoradiography revealed an extensive localization of tritium in the nuclear
      regions. The label could not be removed by treatment with ribonuclease or dilute
      perchloric acid, but quantitative removal from the cells could be effected with
      deoxyribonuclease. Chemical and radioactivity determinations on nucleic acids
      isolated from the exposed HeLa cells revealed the presence of tritium in all 4
      DNA bases. About 12 microg. of tritiated DNA was recovered from 6 x 10(6) HeLa
      cells which had been exposed for 24 hours to 240 microg. of the human DNA. From
      this, it is concluded that the amount of DNA, or its degradation products, taken
      up by the cells was equivalent to at least 10 per cent of the normal HeLa cell
      complement.

PMID- 19866580
TI  - PERIODIC INDUCTION OF DEOXYRIBONUCLEASE ACTIVITY IN RELATION TO THE MITOTIC
      CYCLE.
AB  - The behavior of developing anthers has been studied with respect to
      deoxyribonuclease. This enzyme, in contrast to related hydrolytic ones, is
      sharply periodic in its activity. Whenever a pool of deoxyribosides appears in
      situ, it is preceded by the appearance of deoxyribonuclease. The duration of pool
      or enzyme does not exceed and is generally less than 12 hours, even though the
      life span of the cells concerned is of the order of 25 to 30 days. The
      significance of periodic enzyme induction is discussed in relation to cell
      morphogenesis.

PMID- 19866581
TI  - THE ULTRASTRUCTURE OF MAMMALIAN CARDIAC MUSCLE.
AB  - Papillary muscles of rat and dog hearts were fixed in such a way as to prevent
      excessive shortening during the procedure. The material was embedded in either
      araldite or methacrylate and was stained in various ways. The filamentous fine
      structure of mammalian cardiac muscle is similar to that previously described for
      striated skeletal muscle. The sarcomeres are composed of a set of thick and thin
      filaments which interdigitate in the A band proper. The filament ratios and the
      filamentous array are in accord with those found in skeletal muscle. The
      functional significance of this twofold array of filaments is not entirely clear.
      Various other structural aspects of cardiac cells such as surface membranes,
      mitochondria, nuclei, and cytoplasmic granules are described. The sarcoplasmic
      reticulum is discussed in detail as are the various structural components forming
      the intercalated discs. Fairly frequent deep invaginations of the sarcolemma with
      basement membrane are observed in addition to the intercalated discs. These
      surface membrane invaginations probably explain the branching appearance of
      cardiac fibers as seen under the light microscope.

PMID- 19866582
TI  - STUDIES ON THE PROBLEM OF PRESERVATION OF MYELIN SHEATH ULTRASTRUCTURE:
      EVALUATION OF FIXATION, DEHYDRATION, AND EMBEDDING TECHNIQUES.
AB  - Currently accepted methods of tissue preparation for electron microscopy result
      in alterations of myelinated nerve fibers. In an attempt to minimize distortion
      of myelin, various fixation techniques, dehydration schedules, and embedding
      methods have been evaluated. It was found that the major damage to myelinated
      nerves occurs in the embedding procedure. A technique for embedding nerve tissue
      using the polyester Vestopal W is described which was found to result in improved
      preservation of myelin.

PMID- 19866583
TI  - TIMING OF DNA SYNTHESIS IN THE MITOTIC CYCLE IN VITRO.
AB  - A study was made of the timing of DNA synthesis in the mitotic cycle under
      conditions where the average mitotic cycle of populations of human amnion and
      kitten lung cells in culture was variable. Three types of experiments were
      performed: (a) Autoradiographs were made of incorporated tritiated thymidine in
      cells whose mitotic histories were recorded microcinematographically allowing the
      measurement of telophase + G1 along with the total length of the mitotic cycle.
      (b) Measurement of the G2 + prophase part of the mitotic cycle was performed
      under various conditions by exposing cells to tritiated thymidine and observing
      the increase in labeled metaphases plus anaphases as a function of time. (c) The
      effect of a change in pH on parts of the mitotic cycle was tested by continuously
      photographing a single colony of cells first at pH 7.8 and then at pH 7.1. All of
      our data point to the same conclusion; namely, that within a population of cells
      with a given generation time, the length of each of the measurable parts of the
      mitotic cycle has a particular distribution of values and that, when there is a
      change in the generation time, under our conditions only the T + G1 distribution
      changes.

PMID- 19866584
TI  - THE PROPERTIES OF SPECIFIC STAINS FOR ELECTRON MICROSCOPY PREPARED BY THE
      CONJUGATION OF ANTIBODY MOLECULES WITH FERRITIN.
AB  - In order to take full advantage of recent developments in the electron
      microscopic examination of cellular ultrastructure and composition, it is
      necessary to develop specific electron stains capable of identifying and
      localizing a wide variety of macromolecular components of cells. To this end,
      antibody conjugates have been prepared by chemically coupling the highly electron
      scattering ferritin molecule to antibody. Antigen-antibody precipitations with
      these ferritin-antibody conjugates have demonstrated that under the appropriate
      conditions they retain the specific binding properties of the antibody from which
      they are prepared. An electron microscopic study has been made of aggregates of
      tobacco mosaic virus and its ferritin-conjugated antibody. The aggregates were
      prepared in solution and then sprayed onto specimen screens. The electron
      micrographs reveal that the conjugate specifically attached to, and delineated,
      the virus rods. The chemistry, structure, and resolving power of the ferritin
      antibody conjugates, the specificity of their reactions with homologous antigen,
      and the nature of the problems to be faced in application of these conjugates to
      the study of the internal antigens of cells are discussed.

PMID- 19866585
TI  - ELECTRON MICROSCOPY OF CULTURED SPHERULES OF COCCIDIOIDES IMMITIS.
AB  - Spherules of C. immitis have been grown in vitro in modified Roessler's medium
      under CO(2) tension and continuous cultures now maintained for over 18 months.
      Transformation of hyphae and development of the spherule form have been studied
      by thin section electron microscopy. Cells of organisms in the hyphal stage have
      thin (ca. 50 mmicro), apparently structureless walls and a cytoplasmic membrane.
      Many nuclei, elongated mitochrondria with both transverse and longitudinal
      cristae, and lipid particles are present. The hyphal wall thickens and the cell
      transforms into spherules. A large central accumulation of electrontransparent
      polysaccharide appears in the spherule. The peripheral cytoplasm contains nuclei,
      each enclosed in a double-layered membrane, mitochondria, and small dense
      particles. Prior to cleavage the polysaccharide droplets are lost, while
      mitochrondria become small and spherical. Endospores are formed and liberated
      when the spherule wall breaks. These begin to grow and repeat the cleavage cycle.

PMID- 19866586
TI  - RELATION BETWEEN WATER PERMEABILITY AND INTEGRITY OF SULFHYDRYL GROUPS IN
      MALIGNANT AND NORMAL CELLS.
AB  - When malignant cells, animal and human, were exposed in vitro to solutions of
      heavy metals or other selected compounds, three types of cell blebs were
      produced: (1) acentric blebs, arising from one side of the cell, e. g., by
      chlormerodrin, meralluride sodium, mercuric chloride; (2) symmetrical blebs;
      which completely enveloped the cell, e. g., by strong silver protein, auric
      chloride, p-chloromercuribenzoate; (3) scallop blebs, numerous small spherical
      elevations which completely covered the cell, e.g., by N-ethyl-maleimide,
      trivalent arsenicals, iodoacetamide. As indicated by vital stains and morphologic
      appearance, the blebs arose in healthy cells. They also can be made to appear in
      vivo in ascites tumor cells by intraperitoneal administration of a blebbing
      agent. All the bleb-producing chemicals have the property of reacting with
      protein-sulfhydryl groups by alkylation, oxidation or mercaptide formation. The
      three bleb types have been induced in 8 mouse and 2 rat ascites tumor cells; in 4
      human and 1 mouse malignant cell lines; and in 3 normal cell lines grown in
      tissue culture. In contrast, cells from normal solid tissues of liver, lung,
      spleen, kidney, testis and brain from mouse, rat and rabbit failed to produce
      blebs. A possible interpretation for these observations is presented.

PMID- 19866587
TI  - CYTOPLASMIC INCLUSION BODIES IN CORTISOL-TREATED MAMMARY TUMORS OF C3H/Crgl MICE.

PMID- 19866588
TI  - MAPPING OF LARGE AREAS WITH THE ELECTRON MICROSCOPE.

PMID- 19866589
TI  - ANGULAR LIGHT-SCATTERING STUDIES ON ISOLATED MITOCHONDRIA.
AB  - Angular light-scattering studies have been carried out on suspensions of isolated
      rat liver mitochondria. The angular scatter pattern has a large forward
      component, typical of large particles. Changes in dissymmetry and in the
      intensity of light scattered at 90 degrees have been correlated with changes in
      optical density during the course of mitochondrial swelling and contraction. Such
      changes can be measured at mitochondrial concentrations much below those required
      for optical density measurements. Changes in mitochondrial geometry caused by
      factors "leaking" from mitochondria, not detectable by optical density
      measurements, have been demonstrated by measuring changes in dissymmetry. Angular
      light-scattering measurements therefore offer the advantages of increased
      sensitivity and of added indices of changes in mitochondrial conformation.

PMID- 19866590
TI  - OBSERVATIONS ON THE UPTAKE OF TRITIATED THYMIDINE IN THE PRONUCLEI OF FERTILIZED
      SAND DOLLAR EMBRYOS.
AB  - Following fertilization of the egg of the sand dollar Echinarachnius parma,
      tritiated thymidine (H(3)TDR) was taken up independently by the male and female
      pronuclei beginning within about 15 to 20 minutes, and the labeled pronuclei
      fused at about 30 to 40 minutes. At cleavage 90 minutes later the labeled nuclear
      material was distributed to both daughter cells. Unfertilized eggs and sperm
      exposed to H(3)TDR did not show nuclear localization of thymidine. DNA
      replication, thus, is initiated in the haploid pronuclei shortly after
      fertilization and prior to fusion. The major portion of DNA synthesis, as
      evidenced by thymidine uptake, appears to be during a 20 to 30 minute period
      after fertilization. Fertilization is associated with the activation of a
      mechanism which initiates early and independent replication of DNA in both the
      male and female pronuclei.

PMID- 19866591
TI  - THE PLASMA MEMBRANE OF STAPHYLOCOCCUS AUREUS.

PMID- 19866592
TI  - THE STRUCTURE OF INSECT FIBRILLAR FLIGHT MUSCLE : A Study Made with Special
      Reference to the Membrane Systems of the Fiber.
AB  - The fine structure of fibrillar flight muscle of the mature adult beetle Tenebrio
      molitor is described. Although the very high frequency of contraction of
      fibrillar muscle has previously been in part accounted for as the result of
      mechanical specialization of the wing-bearing segment rather than of a
      correspondingly high rate of motor impulse supply, the problem of the nature of
      the pathway by which excitation is conducted into these large fibers remained.
      Therefore, particular attention has been given to the disposition and
      relationships of the plasma membrane and sarcoplasmic reticulum in this tissue.
      The invading tracheoles draw with them a sheath of plasma membrane from the
      surface to all depths in the fiber, and it is suggested that these sheaths,
      together with the extensive tubular arborisations arising from them, reduce the
      maximum plasma membrane-to-fibril distance from the radius of the fiber to a
      value of less than 2 micro. The evidence presented here confirms Veratti's
      contention that in fibrillar muscle the "reticulum" is associated with, though
      entirely distinct from the fibrils. Unlike other muscles so far examined, these
      flight muscle fibers contain a plasma membrane reticulum only, but it is possible
      that elsewhere the general "sarcoplasmic reticulum" includes a component derived
      from the plasma membrane, likewise acting as the pathway for inward conduction of
      excitation. Profiles of the internalised plasma membrane in Tenebrio showing the
      usual triple-layered 25-25-25 A organization are frequently seen, in sections, in
      close association with isolated vesicles (defined by "simple" 50 A membranes)
      which are here considered to represent, in vestigial form, the portion of the
      sarcoplasmic reticulum which in other types of muscle is complex and highly
      developed. Such associations, in Tenebrio, between these two dissimilar elements
      are here termed "dyads" and the possible morphological and functional homology
      between these and the "triads" of other types of fiber is considered.

PMID- 19866593
TI  - FUNCTIONAL ANALYSIS OF SWIM-BLADDER MUSCLES ENGAGED IN SOUND PRODUCTION OF THE
      TOADFISH.
AB  - A functional analysis of the striated swim-bladder muscles engaged in the sound
      production of the toadfish has been performed by simultaneous recording of muscle
      action potentials, mechanical effects, and sound. Experiments with electrical
      nerve stimulation were made on excised bladder, while decerebrate preparations
      were used for studies of reflex activation of bladders in situ. The muscle twitch
      in response to a single maximal nerve volley was found to be very fast. The
      average contraction time was 5 msec. with a range from 3 to 8 msec., the
      relaxation being somewhat slower. The analysis of muscle action potentials with
      surface electrodes showed that the activity of the muscle fibers running
      transversely to the long axis of the muscle was well synchronized both during
      artificial and reflex activation. With inserted metal microelectrodes monophasic
      potentials of 0.4 msec. rise time and 1.2 to 1.5 msec. total duration were
      recorded. The interval between peak of action potential and onset of contraction
      was only 0.5 msec. Microphonic recordings of the characteristic sound effect
      accompanying each contraction showed a high amplitude diphasic deflection during
      the early part of the contraction. During relaxation a similar but smaller
      deflection of opposite phase could sometimes be distinguished above the noise
      level. The output from the microphone was interpreted as a higher order
      derivative function of the muscle displacement. This interpretation was supported
      by complementary experiments on muscle sound in mammalian muscle. The dependence
      of the sound effects on the rate of muscle contraction was demonstrated by
      changing the temperature of the preparation and, in addition, by a special series
      of experiments with repeated stimulation at short intervals. Results obtained by
      varying the pressure within the bladder provided further evidence for the view
      that the sound initiated in the muscle is reinforced by bladder resonance.
      Analysis of spontaneous grunts confirmed the finding of a predominant sound
      frequency of about 100 per second, which was also found in reflexly evoked
      grunts. During these, muscle action potentials of the same rate as the dominant
      sound frequency were recorded, the activity being synchronous in the muscles on
      both sides. Some factors possibly contributing to rapid contraction are
      discussed.

PMID- 19866594
TI  - A METHOD FOR INTRACELLULAR AUTORADIOGRAPHY IN THE ELECTRON MICROSCOPE.
AB  - A technic is described for high resolution intracellular autoradiography in the
      electron microscope. Cultures of LLC-MK(2) monkey kidney cells were incubated for
      72 hours in a medium containing 0.4 microcurie per ml of thymidine-H(3). After
      labeling, the cells were fixed with osmium tetroxide and embedded in
      methacrylate. Ultrathin sections of the labeled tissue were taken up on Formvar
      coated and carbon-stabilized electron microscope grids. A 150 to 450 A layer of
      silver metal was then evaporated onto the tissue. The coated grids were exposed
      to bromine vapor for 1.5 to 2 minutes under red light, allowed to dry for 1
      minute, and then covered with a thin film of 1 per cent aqueous gelatin applied
      by means of a fine wire loop lowered over the grid supported on a glass peg. For
      autoradiographic exposure, the grids were stored 50 days in a light-proof
      container at 4 degrees C with calcium chloride desiccant. Development was carried
      out for 5 minutes at 20 degrees C in Promicrol (May and Baker, England) diluted
      1:1 with water, followed by a 1 minute water wash and fixation for 2.5 minutes in
      15 per cent aqueous sodium thiosulphate. After removal of the gelatin by
      immersion for 16 hours in water at 37 degrees C, the autoradiograms were dried
      and examined in the electron microscope. Ultrastructural detail was fairly well
      defined and the cytoplasm of each labeled cell was covered with an electron
      opaque deposit of silver, suggesting that a polynucleotide containing thymidine
      may be synthesized in the cytoplasm. The matter is discussed.

PMID- 19866595
TI  - RETICULAR ORGANIZATIONS WITHIN THE STRIATED MUSCLE CELL : An Historical Survey of
      Light Microscopic Studies.

PMID- 19866596
TI  - THE ENDOPLASMIC RETICULUM OF GASTRIC PARIETAL CELLS.
AB  - An electron microscopic survey has been made of the gastric parietal or oxyntic
      cell of the human, cat, beaver, dog, hamster, rat, mouse, and bat, and of the
      corresponding cell type in two species of frog, two species of toad, and the
      horned lizard. A feature consistently found in the parietal cells of the mammals
      or their equivalent in the lower vertebrates is the agranular endoplasmic
      reticulum, which takes the form of branching and anastomosing small tubules
      approximately 200 to 500 A in diameter, sometimes expanded into flattened
      cisternae. In mammalian parietal cells this form of the endoplasmic reticulum is
      found only in limited amounts, but in the corresponding secretory cells of the
      amphibia and reptilia the tubular agranular reticulum is abundant. It is believed
      to comprise a more or less continuous system of channels, but owing to their
      tortuous course only short profiles are seen in thin sections. Immediately
      subjacent to the plasmalemma at the free surface, the cytoplasm is relatively
      free of organelles but is occasionally traversed by the agranular reticulum,
      which appears to be continuous at some points with the cell surface. The possible
      participation of the agranular endoplasmic reticulum in hydrochloric acid
      secretion is discussed.

PMID- 19866597
TI  - CORRELATION OF THE FINE STRUCTURE OF THE GASTRIC PARIETAL CELL (DOG) WITH
      FUNCTIONAL ACTIVITY OF THE STOMACH.
AB  - The fine structure of the parietal (oxyntic) cell in the gastric glands (corpus
      of the stomach) of the dog was examined under conditions of active gastric acid
      secretion and compared with cellular structure in the non-acid-secretory (basal)
      state. Animals, in both acute and chronic experiments, were equipped with gastric
      fistulae so that gastric juice could be collected for analysis of total acidity,
      free acidity, volume, and pH prior to biopsy of the gastric mucosa. The specimens
      of mucosa were fixed in buffered OsO(4) and embedded in n-butyl methacrylate and
      the thin sections were stained with lead hydroxide before examination in the
      electron microscope. A majority of parietal cells showed an alteration of fine
      structure during stimulation of gastric acid secretion by a number of different
      techniques (electrical vagal stimulation, histamine administration, or insulin
      injection). The changes in fine structure affected mainly the smooth surfaced
      vesicular elements and the intracellular canaliculi in the cytoplasm of the cell.
      The mitochondria also appeared to be involved to some extent. During acid
      secretion a greater concentration of smooth surface profiles is found adjacent to
      the walls of the intracellular canaliculi; other parietal cells exhibited a
      marked decrease in number of smooth surfaced elements. Intracellular canaliculi,
      always present in non-acid-secreting oxyntic cells, develop more extensively in
      cells of acid-secreting gastric glands. The surface area of these canaliculi is
      greatly increased by the elaboration of a large number of closely approximated
      and elongated microvilli. Still other parietal cells apparently in a different
      stage of the secretory cycle exhibit non-patent canaliculi lacking prominence;
      such cells have very few smooth surfaced vesicular elements. These morphological
      findings correlated with the acid-secretory state of the stomach provide evidence
      that the parietal cell participates in the process of acid secretion.

PMID- 19866598
TI  - THE FINE STRUCTURE OF BONE CELLS.
AB  - An electron microscopic study of Araldite-embedded, undecalcified human woven and
      chick lamellar bone is presented. The fine structure of the cells of bone in
      their normal milieu is described. Active osteoblasts possess abundant granular
      endoplasmic reticulum, numerous small vesicles, and a few secretion droplets.
      Their long cytoplasmic processes penetrate the osteoid. The transition of
      osteoblasts into osteoid osteocytes and then into osteocytes is traced and found
      to involve a progressive reduction of cytoplasmic organelles. Adjoining the
      osteocytes and their processes is a layer of amorphous material which is
      interposed between the cell surfaces and the bone walls of their respective
      cavities. Osteoclasts contain numerous non-membrane-associated ribosomes,
      abundant mitochondria, and little granular endoplasmic reticulum, thus differing
      markedly from other bone cells. The brush border is a complex of cytoplasmic
      processes adjacent to a resorption zone in bone. No unmineralized collagen is
      seen at resorption sites and it appears that collagen is removed before or at the
      time of mineral solution. All bone surfaces are covered by cells, some of which
      lack distinctive qualities and are designated endosteal lining cells. The
      structure of osteoid, bone, and early mineralization sites is illustrated and
      discussed.

PMID- 19866599
TI  - CHROMATOPHORE DEVELOPMENT, PITS, AND OTHER FINE STRUCTURE IN THE RED ALGA,
      LOMENTARIA BAILEYANA (HARV.) FARLOW.
AB  - Thin sections of the red alga, Lomentaria baileyana, a tubular member of the
      Rhodymeniales, were examined after permanganate fixation and Araldite embedding.
      Many of the cellular structures in Lomentaria were found to be similar to
      analogous structures in animals and higher plants. However, in the walls between
      cells are modified areas generally known as pits which are unique to the higher
      orders of red algae (Florideae). In this study the pits were found to consist of
      a plug-like structure surrounded by an uninterrupted membrane apparently
      continuous with the plasma membrane. Examination of the chromatophore revealed a
      characteristic limiting membrane, a relatively sparse distribution of plates, no
      grana, and a single disc apparently oriented parallel to the limiting membrane.
      In addition to their origin from non-lamellate proplastids, chromatophores were
      found capable of division by simple constriction. Floridean starch grains were
      observed outside the chromatophore and the possibility of an association of the
      first formed grains with portions of the endoplasmic reticulum is considered.
      Gland cells seem to have a high proportion of Golgi components (dictyosomes), and
      are believed to have some kind of secretory function. Many of the Golgi vesicles
      seem to open on the wall and presumably discharge their contents.

PMID- 19866600
TI  - FUNCTIONAL EVIDENCE FOR THE EXISTENCE OF A THIRD CELL TYPE IN THE RENAL
      GLOMERULUS : Phagocytosis of Filtration Residues by a Distinctive "Third" Cell.
AB  - TWO TYPES OF CELLS CAN BE RECOGNIZED ON THE LUMINAL SIDE OF THE GLOMERULAR
      BASEMENT MEMBRANE: the superficial endothelial cells which directly line the
      lumen and are comparable to endothelia lining the capillaries of other tissues,
      and the deep cells, ordinarily not in contact with the lumen, which are
      distinguished by their long cytoplasmic arms extending for some distance in
      several directions along the capillary wall, numerous spinous processes, and
      occasional intraluminal pseudopodia. Experiments carried out with electron-opaque
      tracers indicated that a functional distinction, based on extent of phagocytosis,
      can be made between the superficial and deep cells, thus supporting the existence
      of a distinctive "third" cell (in addition to endothelium and epithelium) in the
      renal glomerulus. Ferritin, colloidal gold, or thorotrast was administered
      intravenously to normal and, in the case of ferritin, to nephrotic rats. Kidney
      tissue was fixed at selected intervals from 1 hour to 10 days after the injection
      and studied by electron microscopy. Within 1 to 4 hours after tracer
      administration, the particles which did not traverse the glomerular capillary
      wall gradually accumulated in the less compact, inner strata of the basement
      membrane and the large spongy areas of axial regions. After 1 day the
      concentration of circulating tracer declined and the peripheral areas of the
      capillaries became relatively free of particles while large accumulations
      developed in the axial regions. During this period increasing quantities of
      ferritin were taken up by the deep cells and were found within large and small
      sized invaginations of their cell membrane or concentrated within cytoplasmic
      vesicles, vacuoles, multivesicular and dense bodies. At the same time the deep
      cells showed increased numbers of intraluminal pseudopodia. Within 2 to 4 days
      the deposits in the spongy areas were cleared and concomitantly increased
      quantities of tracer appeared in the deep cells within dense cytoplasmic bodies,
      some of which were more compact than before. When ferritin was given to nephrotic
      animals the sequence of events was generally the same except that the ferritin
      deposits at any given period were more massive, their incorporation into the deep
      cells occurred primarily by means of large pockets 1 to 2 micro in diameter and
      their clearance from the spongy areas was slower. In normal as well as in
      nephrotic animals, the phagocytic activity of the superficial endothelium was
      negligible when compared to that of the deep cells.

PMID- 19866601
TI  - SYNTHESIS OF DEOXYRIBONUCLEIC ACID BY MICRO- AND MACRONUCLEI OF TETRAHYMENA
      PYRIFORMIS.
AB  - Evidence as to the times of DNA synthesis in micronucleate Tetrahymena pyriformis
      (mating type II, variety 1) has been obtained by briefly exposing individuals of
      different ages to tritiated thymidine, returning them to non-radioactive medium,
      fixing at division, and preparing autoradiographs. A variable length of
      interphase, ranging from a few minutes to about 2 hours, has been found to
      precede the initiation of macronuclear DNA synthesis. Once begun, however, the
      period of synthesis appears to be similar in all cells, regardless of generation
      time, and has been estimated at 1 to 1(1/2) hours. Under the conditions of these
      experiments, the time elapsing between the end of synthesis and subsequent
      division into daughter cells ranges from approximately 1(1/2) to 2(1/2) hours in
      generation times long enough to allow such variability. Division of the
      micronucleus occurs shortly before the cell begins to divide; its DNA synthesis
      starts immediately and continues after cell division for a total period estimated
      at about an hour.

PMID- 19866602
TI  - ATPASE ACTIVITY ON THE INTERCALATED DISC AND C(z) BANDS OF MOUSE HEART MUSCLE.

PMID- 19866603
TI  - ELECTRON MICROSCOPY OF THE OXYNTIC CELL IN THE GASTRIC GLANDS OF THE BULLFROG,
      RANA CATESBIANA: III. Permanganate Fixation of the Endoplasmic Reticulum.

PMID- 19866604
TI  - THE BASE COMPOSITION OF NUCLEIC ACIDS IN CHROMOSOMES, PUFFS, NUCLEOLI, AND
      CYTOPLASM OF CHIRONOMUS SALIVARY GLAND CELLS.
AB  - The base composition of RNA from individually isolated giant chromosomes, puffed
      chromosome segments, nucleoli, and samples of cytoplasm from Chironomus salivary
      gland cells was determined by microelectrophoresis. Data on the adenine: guanine
      quotient of the chromosomal DNA were also obtained. The results show that: 1)
      Chromosomal, nucleolar, and cytoplasmic RNA's differ significantly from each
      other in base composition. 2) Nucleolar and cytoplasmic RNA's, in spite of the
      difference, show great similarities with regard to the base composition and are
      both rich in adenine and uracil. 3) The RNA extracted from chromosome I differs
      significantly from the RNA's extracted from different segments of chromosome IV,
      and the latter differ significantly from each other. 4) The values for the RNA:
      DNA quotients of chromosome segments parallel the development of synthetically
      active genes, so-called Balbiani rings. 5) The chromosomal RNA does not show a
      base symmetry in any of the investigated cases, nor is the content of guanine +
      cytosine the same as that for DNA. The first of these two facts excludes the
      possibility that the chromosomal RNA is a complete copy of both strands of the
      chromosomal DNA. In spite of the difference in guanine + cytosine content between
      the two nucleic acids the RNA may still partly or completely be a single strand
      copy depending upon how representative the DNA values are for the synthetically
      active DNA.

PMID- 19866605
TI  - ADENOSINE TRIPHOSPHATE-LINKED CONCENTRATION OF CALCIUM IONS IN A PARTICULATE
      FRACTION OF RABBIT MUSCLE.
AB  - ATPase and ATP-dependent calcium ion concentration was studied with a membrane
      fraction isolated from homogenized rabbit skeletal muscle by differential
      centrifugation. Electron micrographs of the fraction indicate that it consists
      mainly of resealed tubules and vesicles of the endoplasmic reticulum. The up-to
      1400-fold concentration of calcium in this fraction might be explained by
      proposing the existence of an energy-requiring system for the transport of
      calcium ions into the tubules or vesicles.

PMID- 19866606
TI  - THE FINE STRUCTURE OF THE PIGMENT EPITHELIUM IN THE ALBINO RAT.
AB  - In this report, particular attention is paid to the inclusion bodies found in the
      apical cytoplasm of the pigment epithelial cell. These bodies are of variable
      size and form. The smallest (0.4 micro diameter) consist of a granular matrix
      enclosed by a single membrane, and are similar to the lysosomes of hepatic cells.
      Larger inclusion bodies contain areas of lamellated material in addition to
      granular matrix. The largest particles seen (2 micro diameter) are almost
      entirely lamellar. These different forms seem closely related, for it is possible
      to find all transitional stages between the smallest and largest particles. The
      relationship between the lamellar inclusion bodies and the rod outer segments is
      discussed.

PMID- 19866607
TI  - METABOLIC PROPERTIES OF CELLS ISOLATED FROM ADULT MOUSE LIVER.
AB  - Suspensions of isolated cells were prepared from mouse livers that had been
      perfused via the portal vein with a buffered medium containing sucrose. The
      demonstration of metabolic activities in these cells was found to be critically
      dependent on the composition of the suspending medium. The cells showed
      considerable metabolic activity in a simple medium containing 0.06 to 0.20 M
      sucrose, but did not respire in 0.30 M sucrose medium. Endogenous respiration was
      greatest when the sucrose concentration of the medium was 0.10 M or lower and was
      associated with the formation of acetoacetate. The cells oxidized citric acid
      cycle intermediates, glutamate, lactate, pyruvate, beta-hydroxybutyrate, alpha
      glycerophosphate, and fatty acids and synthesized urea from ammonium chloride,
      but carbohydrate substrates did not stimulate oxygen uptake. Cells incubated in
      Krebs' phosphate-saline did not respire. The lack of respiration in this medium
      is thought to be related to increased permeability of the cell membrane with
      penetration of calcium ions and orthophosphate into the cells causing
      mitochondrial swelling and destruction. Further evidence for the loss of cellular
      permeability barriers is provided by the demonstration of leakage of certain
      soluble enzymes into the preparative media.

PMID- 19866608
TI  - A MASKING TECHNIQUE FOR CONTRAST CONTROL IN ELECTRON MICROGRAPHS.

PMID- 19866609
TI  - THE STRUCTURE OF POSSIBLE PHOTORECEPTIVE ELEMENTS IN THE SIXTH ABDOMINAL GANGLION
      OF THE CRAYFISH.

PMID- 19866610
TI  - FINE STRUCTURE OF CELLS ISOLATED FROM ADULT MOUSE LIVER.
AB  - Suspensions of isolated cells in various media were prepared from mouse liver
      which had been perfused via the portal vein with a buffered medium containing
      0.40 M sucrose, and the cells were fixed with osmium tetroxide. Their fine
      structure was compared with that of cells from perfused and unperfused intact
      liver. Perfusion brought about some separation of the cells with little or no
      damage to cell membranes. When cells were dispersed in 0.40 M sucrose medium the
      plasma membranes partially broke down, and this disintegration was increased by
      transfer of the cells to media of lower osmolarity. This is presumed to account
      for the loss of permeability barriers which occurs in isolated liver cells. The
      mitochondria in cells of perfused liver and in isolated cells remained elongated,
      but the layers of many mitochondrial cristae became separated by clear spaces.
      When cells were transferred to a medium containing 0.20 M sucrose, the
      mitochondria swelled and became spherical, often with displacement of the swollen
      cristae to the periphery. In a medium containing 0.06 M sucrose and 0.08 M
      potassium chloride the outer chamber of many mitochondria became swollen with
      displacement of the mitochondrial body to one side to give a crescent-shaped
      appearance. These changes in mitochondrial morphology are discussed in relation
      to the metabolic activity of isolated liver cells.

PMID- 19866611
TI  - CYTOLOGICAL STUDIES ON TWO FUNCTIONAL HEPATOMAS : Interrelations of Endoplasmic
      Reticulum, Golgi Apparatus, and Lysosomes.
AB  - The Reuber hepatoma H-35 and Morris hepatoma 5123 have been studied by electron
      microscopy and by cytochemical staining methods for a number of phosphatases.
      These studies emphasize the resemblances of the two tumors to rat liver, but they
      also indicate distinctive features in each of the three tissues. Secretory
      product accumulates within the cisternae of the Golgi apparatus that dilate to
      form the Golgi vacuoles. The vacuoles apparently separate, and secretory material
      undergoes further condensation within them. These "secretory vacuoles" possess
      acid phosphatase activity and may thus be considered lysosomes. The membranes of
      the Golgi apparatus are without acid phosphatase activity but show high levels of
      thiaminepyrophosphatase activity. The endoplasmic reticulum also hydrolyzes
      thiaminepyrophosphate but at a lower rate; it hydrolyzes the diphosphates of
      uridine, guanosine, and inosine rapidly. These observations and the electron
      microscopic images are consistent with the view that the cytomembranes are in a
      dynamic state of flux, movement, and transformation in the living cell, and that
      smooth surfaced derivatives of the endoplasmic reticulum become refashioned into
      the Golgi membranes as the Golgi membranes are being refashioned into those that
      delimit secretory vacuoles. The variations encountered in the two hepatomas are
      described. The electron microscope literature dealing with the relations of the
      Golgi apparatus to secretory granules, on the one hand, and the endoplasmic
      reticulum, on the other, is reviewed briefly.

PMID- 19866612
TI  - THE EXTRACELLULAR SPACE IN THE TOAD RETINA AS DEFINED BY THE DISTRIBUTION OF
      FERROCYANIDE : A Light and Electron Microscope Study.
AB  - Measurements of the uptake of compounds that ordinarily do not penetrate into
      cells have been a source of data on the size of the extracellular space in
      nervous tissue. The distribution of one such compound, ferrocyanide, has been
      studied in the toad retina by means of the light and electron microscopes. At the
      level of the light microscope, ferrocyanide, detected as Prussian blue, appears
      to penetrate predominantly within the inner processes of Muller cells. A diffuse
      background staining by Prussian blue can be noticed also at the inner retinal
      layers. At the level of the electron microscope, Muller cells exhibit an
      extensively developed system of channels which are formed by infoldings of the
      plasma membrane. Ferrocyanide, detected as copper ferrocyanide deposits, is found
      occupying the lumina of these channels and in the narrow intercellular gaps of
      the retina. These observations indicate that in the toad retina the extracellular
      medium includes the intercellular spaces plus a glial compartment formed by the
      infoldings of the plasma membrane of the Muller cells.

PMID- 19866613
TI  - A METHOD FOR THE QUANTITATIVE ESTIMATION OF CYTOPLASMIC STRUCTURES.
AB  - A sampling procedure and calculations are described by which electron micrographs
      of cytoplasmic structures may be quantitatively analyzed. The relative areas
      occupied by formed bodies and by the "membrane space," the remainder of the
      cytoplasm, are evaluated. A method for making a measurement of the quantity of
      endoplasmic reticulum or other membrane profiles is described. The technic and
      results are illustrated with normal rat liver cells.

PMID- 19866614
TI  - ENZYME-STRUCTURE RELATIONSHIPS IN THE ENDOPLASMIC RETICULUM OF RAT LIVER : A
      Morphological and Biochemical Study.
AB  - Subfractionation of preparations of rat liver microsomes with a suitable
      concentration of sodium deoxycholate has resulted in the isolation of a membrane
      fraction consisting of smooth surfaced vesicles virtually free of
      ribonucleoprotein particles. The membrane fraction is rich in phospholipids, and
      contains the microsomal NADH-cytochrome c reductase, NADH diaphorase, glucose-6
      phosphatase, and ATPase in a concentrated form. The NADPH-cytochrome c reductase,
      a NADPH (or pyridine nucleotide unspecific) diaphorase, and cytochrome b(5) are
      recovered in the clear supernatant fraction. The ribonucleoprotein particles are
      devoid of, or relatively poor in, the enzyme activities mentioned. Those enzymes
      which are bound to the membranes vary in activity according to the structural
      state of the microsomes, whereas those which appear in the soluble fraction are
      stable. From these findings the conclusion is reached that certain enzymes of the
      endoplasmic reticulum are tightly bound to the membranes, whereas others either
      are loosely bound or are present in a soluble form within the lumina of the
      system. Some implications of these results as to the enzymic organization of the
      endoplasmic reticulum are discussed.

PMID- 19866615
TI  - A STUDY OF THE NUCLEOSIDE TRI- AND DIPHOSPHATE ACTIVITIES OF RAT LIVER
      MICROSOMES.
AB  - Rat liver microsomes catalyze the hydrolysis of the triphosphates of adenosine,
      guanosine, uridine, cytidine, and inosine into the corresponding diphosphates and
      inorganic orthophosphate. The activities are stimulated by Na(2)S(2)O(4), and
      inhibited by atebrin, chlorpromazine, sodium azide, and deaminothyroxine. Sodium
      deoxycholate inhibits the ATPase activity in a progressive manner; the release of
      orthophosphate from GTP and UTP is stimulated by low, and inhibited by high,
      concentrations of deoxycholate, and that from CTP and ITP is unaffected by low,
      and inhibited by high, concentrations of deoxycholate. Subfractionation of
      microsomes with deoxycholate into ribosomal, membrane, and soluble fractions
      reveals a concentration of the triphosphatase activity in the membrane fraction.
      Rat liver microsomes also catalyze the hydrolysis of the diphosphates of the
      above nucleosides into the corresponding monophosphates and inorganic
      orthophosphate. Deoxycholate strongly enhances the GDPase, UDPase, and IDPase
      activities while causing no activation or even inhibition of the ADPase and
      CDPase activities. The diphosphatase is unaffected by Na(2)S(2)O(4) and is
      inhibited by azide and deaminothyroxine but not by atebrin or chlorpromazine.
      Upon fractionation of the microsomes with deoxycholate, a large part of the
      GDPase, UDPase, and IDPase activities is recovered in the soluble fraction.
      Mechanical disruption of the microsomes with an Ultra Turrax Blender both
      activates and releases the GDPase, UDPase, and IDPase activities, and the former
      effect occurs more readily than the latter. The GDPase, UDPase, and IDPase
      activities of the rat liver cell reside almost exclusively in the microsomal
      fraction, as revealed by comparative assays of the mitochondrial, microsomal, and
      final supernatant fractions of the homogenate. The microsomes exhibit relatively
      low nucleoside monophosphatase and inorganic pyrophosphatase activities, and
      these are unaffected by deoxycholate or mechanical treatment. Different
      approaches toward the function of the liver microsomal nucleoside tri- and
      diphosphatases are reported, and the possible physiological role of the two
      enzymes is discussed.

PMID- 19866616
TI  - N-VINYLPYRROLIDONE AS A WATER COMPATIBLE CONSTITUENT OF EMBEDDING RESINS FOR
      SECTIONING IN ELECTRON MICROSCOPY.
AB  - The use as an embedding resin for ultrathin sectioning of a cross-linked triple
      copolymer of N-vinylpyrrolidone, acrylonitrile, and ethylene glycol
      dimethacrylate is described. The first of these components is miscible with
      water, in all proportions, and can be used as a dehydrating agent, or,
      alternatively, ethanol may be used in the standard way. Polymerization is carried
      out at 37 degrees C or even lower temperatures. This resin is unsuitable for use
      after osmium fixatives, but after permanganates it gives results similar to
      epoxy. Photographs of rye root-tip cells fixed in permanganate and sectioned in
      this resin are presented. Because of the water-permeable nature of the product
      and low polymerization temperature, this resin appears to have possibilities for
      histochemistry.

PMID- 19866617
TI  - FINE STRUCTURE OF MYCOTA : 4. The Occurrence of the Golgi Dictyosome in the
      Fungus Neobulgaria pura (Fr.) Petrak.
AB  - Though the dictyosome of the Golgi apparatus appears to be generally distributed
      in plant and animal cells, it is here described for the first time in the fungi.
      The present report illustrates, in electron micrographs of thin sections, the
      characteristic structure of the Golgi dictyosome in a special cell type of a
      supporting pseudo-tissue (the inner ectal excipulum) of a highly evolved
      Ascomycete, Neobulgaria pura (Fr.) Petrak, a monotypic discomycete. This
      organelle may secrete the gelatinous matrix filling the cup formed by the inner
      ectal excipulum. All the other cells in this species appear more typical of
      fungal cells; i.e., they have no dictyosome and, unlike the cup-forming cells,
      they show characteristic continuities of the plasma membrane with the perinuclear
      cisternae. The dictyosome, in those cells in which it appears in this fungus, is
      formed by a series of vesiculations of the outer component of the nuclear
      envelope that align to form a stack of sacs. The sacs near the nucleus are
      flattened (by what appears to be an intermembrane cement) while those near the
      plasma membrane are more distended. These observations suggest three
      possibilities: first, fungi may be more closely related to other eukaryotic cells
      than previously suspected from electron microscopic studies; second, the outer
      nuclear membrane may have been the primitive precursor of the dictyosome; and
      third, the inverse relationship of the occurrence of the nuclear membrane plasma
      membrane continuities and the dictyosome suggests that the latter may have
      evolved as a means of removing from the cell the products of reactions occurring
      on a discontinuous membrane system.

PMID- 19866618
TI  - ASYNCHRONY OF DNA SYNTHESIS IN CHROMOSOMES OF HUMAN DIPLOID CELLS.

PMID- 19866619
TI  - ELECTRON MICROSCOPIC AUTORADIOGRAPHY : An Improved Technique for Producing Thin
      Films and Its Application to H-Thymidine-Labeled Maize Nuclei.
AB  - An improved method has been developed for the preparation of autoradiographs for
      electron optical study. The refinement lies principally in the routine production
      of uniformly thin layers of photographic emulsion over the tracer-labeled cell
      sections. This is accomplished by means of a centrifugal spreading mechanism.
      Maize root tips grown in the presence of H(3)-thymidine were examined electron
      microscopically by this technique and were found to display nuclear labeling with
      impressive clarity. The new procedure utilized here yields objects in which the
      finest cell structures are easily resolvable without recourse to gelatin
      digestion techniques.

PMID- 19866620
TI  - CHEMICAL AND MORPHOLOGICAL STUDIES ON THE IN VITRO CALCIFICATION OF AORTA.
AB  - After a lag period, rat aortas incubated in rat serum in vitro accumulated
      substantial quantities of calcium and phosphate. Examination of the tissue by x
      ray diffraction, microradiography, electron diffraction, and electron microscopy
      indicated that the calcium-phosphate phase which formed was hydroxyapatite and
      that the crystals were localized almost exclusively in elastin. Selective
      elimination of various components of the aorta with proteolytic enzymes indicated
      that the presence of elastin was required for mineralization. Collagen fibers did
      not appear to be required for the initiation of calcification, nor did they seem
      to undergo appreciable calcification in the time periods studied. Analysis of the
      initial lag period suggested that at least two changes occurred in serum prior to
      the mineralization of this tissue. Inhibitors of the reaction were destroyed, and
      the level of dialyzable calcium was elevated owing to its release from serum
      protein.

PMID- 19866621
TI  - THE ORGANIZATION AND INNERVATION OF THE LUMINESCENT ORGAN IN A FIREFLY, PHOTURIS
      PENNSYLVANICA (COLEOPTERA).
AB  - The organization of the luminescent organ of an adult firefly has been studied
      with the electron microscope, and particular attention has been given to the
      disposition of nerve terminals within the organ. The cytological structure of the
      cells of the tracheal system, the peripheral and terminal axons, the photocytes
      and the cells of the dorsal ("reflecting") layer is described. Previous
      observations on the peripheral course of nerve branches alongside the tracheal
      trunks at the level of the dorsal layer and photocyte epithelium have been
      confirmed, and specialised nerve endings containing axoplasmic components
      structurally identical with "synaptic vesicles" and "neurosecretory droplets"
      have been identified, not in association with the surface of the photocytes, but
      lying between the apposed surfaces of two components of the tracheal epithelium:
      the tracheal end-cell and the tracheolar cell. These cytological findings are
      discussed in terms of available biochemical and physiological evidence concerning
      the mechanism of light emission in the firefly, especially with respect to the
      possible role of chemical "transmitter" action in triggering a response in a
      luminescent effector system.

PMID- 19866622
TI  - NEGATIVE STAINING OF THINLY SPREAD CELLS AND ASSOCIATED VIRUS.

PMID- 19866623
TI  - TECHNICAL MODIFICATIONS IN MARAGLAS EMBEDDING.

PMID- 19866624
TI  - THE FINE STRUCTURE OF THE CELL BOUNDARY OF THE BLUE-GREEN ALGA ANACYSTIS MONTANA.

PMID- 19866625
TI  - CYTOCHEMICAL STUDIES OF THE NUCLEOPROTEINS OF HELA CELLS INFECTED WITH HERPES
      VIRUS.
AB  - The morphological and cytochemical changes in HeLa cells infected with herpes
      virus have been studied at frequent intervals during infection and related to the
      growth of virus and the multiplicity of the virus inoculum. Infection with a high
      multiplicity inoculum produced enlargement and extrusion of small
      ribonucleoprotein (RNP) bodies in the nucleoli (nucleolini) to form RNP bodies in
      the nucleoplasm (B bodies) beginning (1/2) hour after infection. 3 hours after
      infection, RNP of the pars amorpha appeared to diffuse into the adjacent
      nucleoplasm, where, (1/2) hour later, the classical type A inclusion or A body
      first appeared. The A bodies displaced the B bodies and the nucleoli and
      eventually filled the nucleus. 6 hours after infection, minute granules
      containing RNA, DNA, and non-histone protein appeared inside the A bodies (A
      granules) and increased in number until the late stages of infection, when they
      disappeared. 18 hours after infection, at the time when the A bodies came to fill
      the nucleus completely, extrusion of RNP from the nucleus produced cytoplasmic
      masses which have been termed C bodies. B bodies were formed in the majority of
      cells before the maturation of infectious virus, but the number of B bodies could
      not be correlated with the amount of virus in the cell or with the multiplicity
      of the inoculum. It is suggested that the formation of B bodies may be the result
      of inhibition of the onset of mitotic division by a mechanism which does not
      inhibit the formation of RNA in the nucleolini. The nature of the A bodies, the A
      granules, and the C bodies is discussed and it is concluded that the A granules
      may represent aggregations of maturing virus in the nucleus. The progression of
      some C mitotic metaphases to the formation of post-C mitotic multinucleated giant
      cells is described. These are distinct from syncytia formed by cell fusion.

PMID- 19866626
TI  - THE EFFECTS OF CARBON MONOXIDE INHIBITION ON ATP LEVEL AND THE RATE OF MITOSIS IN
      THE SEA URCHIN EGG.
AB  - The requirements for ATP synthesis during the various phases of mitosis were
      investigated in the oxygen-requiring eggs of the sea urchin, Strongylocentrotus
      purpuratus. CO in the dark, a specific inhibitor of respiration, was used to
      inhibit ATP synthesis. The kinetics of respiratory inhibition were determined by
      analyzing ATP levels with the luciferin-luciferase assay. The kinetics of mitotic
      inhibition were determined by analysis of the rate of mitosis. It was found that
      CO inhibition resulted in a decrease in the normal ATP level. Coincident with
      this decrease was a decrease in the rate of mitosis which stops completely when
      the ATP drops below 50 per cent of the normal level. With the use of various
      degrees of CO inhibition, the rate of mitosis is shown to be related to the
      resultant ATP level. These results contradict the basic premise of the energy
      reservoir hypothesis, and also disagree with other reports that cells in mitosis
      are insensitive to inhibitors of energy metabolism. Data are presented which
      demonstrate that these conflicting reports result from insufficient inhibition of
      ATP synthesis. The above findings all indicate that mitosis depends on the
      continuous synthesis and utilization of ATP.

PMID- 19866627
TI  - AN ELECTRON MICROSCOPE STUDY OF DENERVATION ATROPHY IN RED AND WHITE SKELETAL
      MUSCLE FIBERS.
AB  - A study, mainly by electron microscopy, has been made on two leg muscles of rat,
      in the course of atrophy experimentally induced by total denervation. As a
      preliminary the chief distinctive features of the soleus, chosen as a
      representative of pure red muscle, and of the gastrocnemius, representative of
      pure white muscle, are described. Two major phases of atrophy, somewhat
      overlapping in time, were observed. In the first, a degenerative autolytic
      process takes place in areas of the fiber, with loss of striation. It can be
      detected as early as the 7th day, but the maximum is observed at the 14th day,
      and accounts for a gross weight loss of 50 per cent. The first alteration appears
      in the Z lines; disorder in the disposition of filaments then follows. The
      process occurs very rapidly, leaving large areas in the cell in which one can
      detect only ground substance, glycogen, rare randomly disposed vesicular
      elements, and some mitochondria. Several lysosomes and masses of lipoproteins,
      which assume the configuration of concentric lamellae, show up in these fibers.
      Subsequently large parts of the waste sarcoplasm are discarded into the
      intercellular spaces. In the second major phase the so called "simple" atrophy
      takes place. The process starts early, but its effects are more detectable after
      1 month. In this period, single myofibrils undergo different degrees of reduction
      in diameter, while the spatial disposition of primary and secondary filaments
      inside the fibrils remains normal. The appearance of the fibrils in longitudinal
      sections suggests that the process takes place by the detachment of filaments
      from the periphery of the fibrils and by their subsequent breakdown in the
      interfibrillary spaces. The sarcoplasmic reticulum is still well preserved, and
      relatively overdeveloped. Mitochondria disappear in parallel with the contractile
      material.

PMID- 19866628
TI  - FINE STRUCTURE IN FROZEN-ETCHED YEAST CELLS.
AB  - The freeze-etching technique, which is a special kind of freeze-drying, allows
      electron microscopic investigation of cells and tissues in the frozen state. In
      regard to yeast cells (Saccharomyces cerevisiae) a freeze-fixation technique has
      been developed which does not kill the object. The electron micrographs therefore
      are considered to impart an image of high fidelity. The cutting of the frozen
      object, which actually consists of a fine splintering, produces not only cross
      sectional views (cross-fractures) of the structures but also surface views of the
      membranes and organelles. Many surface structures are described which have not
      been shown by the usual sectioning techniques. The cytoplasmic membrane contains
      hexagonal arrangements of particles which are apparently involved in the
      production of the glucan fibrils of the cell wall. Alterations of the
      distribution of nuclear pores are shown in cells of different ages. Freeze
      etching enables a clear distinction of endoplasmic reticulum and vacuoles in
      yeast cells. The membranes of the vesicular systems are covered by ribosomes
      arranged in circular patterns. The mitochondrial envelope shows small
      perforations which could allow the exchange of macromolecules. The storage
      granules consist of concentric layers of lipid, presumably phosphatide. A Golgi
      apparatus has been detected which may be involved in the storage of lipid. The
      structure of the unit membrane and the membrane structures of all organelles as
      revealed by chemical fixation are confirmed in principle. Glycogen agglomerations
      are identified in the ground plasm of older cells. Insight into artifacts
      introduced by common chemical fixation and embedding techniques is obtained and
      discussed.

PMID- 19866629
TI  - THE SARCOPLASMIC RETICULUM OF STRIATED MUSCLE OF A CYCLOPOID COPEPOD.
AB  - The fine structure of the abdominal musculature of the copepod Macrocyclops
      albidus was investigated by electron microscopy. Tubules penetrate into the
      muscle fibers from the sarcolemma, continuity between the wall of the tubules and
      the sarcolemma being clear. A dense network of tubules envelops the myofibrils,
      its interstices being occupied by cisternal elements. At the Z lines the tubules
      traverse the interior of myofibrils, giving off branches which course
      longitudinally within the substance of the myofibrils. These branches are also
      accompanied by elongate, non-intercommunicating cisternae. Comparison of this
      fast acting copepod muscle with other vertebrate and invertebrate muscles
      indicates that the complexity of the tubular system is a function of the
      myofibrillar geometry, whereas the degree of development of the cisternal system
      is related to the contraction speed of the muscle.

PMID- 19866630
TI  - INTERCELLULAR CONNECTIONS IN THE OUTGROWING STOLON OF CORDYLOPHORA.
AB  - Outgrowth of the stolon in the hydroid Cordylophora has been studied at the
      cellular level. Staining experiments and histological examination indicate that
      the generative region of the stolon is at its base where interstitial cells are
      prominent. Cells in the ectoderm at the stolon tip appear to be actively
      synthesizing new perisarc as the tip advances over the substrate, rather than
      involved in proliferation. The fine structure of cellular relationships in these
      regions has been considered and an attempt has been made to correlate the
      structure and distribution of intercellular attachments with these various
      functional zones along the outgrowing stolon. Intercellular attachments are
      similar to those previously described in Hydra, but favorable cases provide a
      more complete description. The series of intercellular septa each consist of two
      electron-opaque bodies lying close together midway between the two plasma
      membranes and separated from the membranes by a region of lesser density. The
      plasma membranes contain electron-opaque and transparent regions which alternate
      with the septa. These regions extend over about 70 A. The position of
      intercellular connections relative to the outer surface of the cenosarc varies in
      different parts of the stolon.

PMID- 19866631
TI  - AN ANALYSIS OF DESMOSOME SHAPE, SIZE, AND ORIENTATION BY THE USE OF HISTOMETRIC
      AND DENSITOMETRIC METHODS WITH ELECTRON MICROSCOPY.
AB  - The probable shape, size, and orientation of desmosomes of the cells comprising
      the secretory tubules in rat submaxillary gland was determined by statistical and
      algebraic methods applied to electron micrographs. It was concluded that these
      desmosomes are discrete ellipsoidal discs whose principal axes are in the order
      of 4100 and 2500 angstrom units, and that they are preferentially oriented with
      their long axis more or less parallel to the base-apex axis of the cell.
      Densitometric interpretation agrees with the statistically based reconstruction
      of desmosomal shape. By densitometric analysis it was also determined that the
      peak to peak distances between layers within these desmosomes are in essential
      agreement with other reported findings. The approach described may have general
      applications to problems in the analysis of submicroscopic morphology.

PMID- 19866632
TI  - THE INDUCTION OF MELANIZATION IN GOLDFISH SCALES WITH ACTH, IN VITRO: Cellular
      and Subcellular Changes.
AB  - The induction of melanization in xanthic goldfish scales with ACTH in vitro has
      been studied by light and electron microscopy utilizing ammoniated silver nitrate
      staining of premelanin and melanin. The melanized cells (melanophores and
      melanocytes) and the yellow pigmented cells (lipophores and the newly described
      lipocytes) were found to possess many similarities at the levels of cellular and
      subcellular structure. The latter cells contain characteristic cytoplasmic bodies
      which react positively to the premelanin stain. Changes accompanying ACTH
      stimulation of goldfish scales in tissue culture suggest that these bodies in the
      lipocytes and lipophores can become melanized. Electron micrographs illustrate
      the intermediate staining of newly formed melanin granules in an induced
      melanocyte and the appearance of a transitional melanolipophore. It is postulated
      that ACTH can promote the association of the enzyme tyrosinase with the preformed
      structure of unmelanized granules.

PMID- 19866633
TI  - THE STRUCTURE OF FLIGHT MUSCLE SARCOSOMES IN THE BLOWFLY CALLIPHORA
      ERYTHROCEPHALA (DIPTERA).
AB  - The electron microscopic structure of sectioned indirect flight muscle fibers of
      the blowfly Calliphora is described. Particular attention is paid to the
      organization of the sarcosomes (mitochondria) of this tissue, and this
      description is accompanied by an account of the appearance of these bodies in
      negatively stained preparations. In sectioned material, it has been shown that
      these sarcosomes are similar to other mitochondria in the disposition of the
      outer and inner limiting membranes, but that the cristae, confluent with the
      latter, are unusually regular, and form parallel plates, containing circular
      fenestrations forming cylindrical channels within the matrix. Negatively stained
      preparations of disrupted sarcosomes reveal that both the outer limiting membrane
      and the cristae membranes bear large numbers of small particles, similar in
      appearance to those described by Fernandez-Morgan and others in various
      mitochondria. In Calliphora, these particles consist of a sub-spherical "head"
      and a cylindrical "stalk," and appear to be arranged on the mitochondrial
      membranes either randomly distributed, or collected into circular or elongated
      groups. Recent suggestions concerning the nature of these submitochondrial
      particles are discussed, and an attempt is made to correlate the aspects of
      organization of Calliphora sarcosomes, revealed by conventional sectioning of the
      "intact" structures, and by negative staining of sarcosomal derivatives.

PMID- 19866634
TI  - THE NUCLEUS OF NOCTILUCA SCINTILLANS: Aspects of Nucleocytoplasmic Exchanges and
      the Formation of Nuclear Membrane.
AB  - The unicellular organism, Noctiluca, has been examined with the electron
      microscope. The nucleus is small compared to the very large size of the cell, but
      the nuclear border has an organization which indicates an active
      nucleocytoplasmic exchange. Whereas annuli are missing over most parts of the
      nuclear membrane proper, there are "annulated vesicles" in a layer inside the
      nuclear membrane. The hypothesis is put forth that nuclear substances move
      through the annuli into these vesicles, and that the annulated vesicles
      themselves are transported through the nuclear membrane. The various forms of the
      annulated vesicles are consistent with this hypothesis. An implication of this
      postulate is the synthesis of annulated membranes inside a closed nucleus which
      are physically separate from the endoplasmic reticulum. The chromosomes are in a
      state resembling prophase chromosomes and are surrounded by granular masses. Only
      a small portion of the entire nuclear volume is occupied by the chromosomes.
      There are many nucleolus-like bodies.

PMID- 19866635
TI  - A "MICROTUBULE" IN PLANT CELL FINE STRUCTURE.
AB  - This paper reports an electron microscope examination of the cortices of some
      plant cells engaged in wall formation. Previous studies of similar material fixed
      in OSO(4) alone have disclosed discontinuities in the plasma membrane and other
      evidence of inadequate fixation. After glutaraldehyde, used as a fixative in this
      present study, the general preservation of cortical fine structure is greatly
      improved. This is shown, for example, by the first evidence of slender tubules,
      230 to 270 A in diameter and of indeterminate length, in plant cells of this
      type. They have been found in the cortical regions of cells of two angiosperms
      and one gymnosperm, representing all the material so far studied following this
      method of fixation. The tubules are identical in morphology to those also
      observed here in the mitotic spindles of plant cells, except that the latter have
      a somewhat smaller diameter. It is noted that the cortical tubules are in a
      favored position to govern cytoplasmic streaming and to exert an influence over
      the disposition of cell wall materials. In this regard it may be of some
      significance that the tubules just beneath the surface of the protoplast mirror
      the orientation of the cellulose microfibrils of the adjacent cell walls.

PMID- 19866636
TI  - HORMONAL CONTROL OF REVERSIBLE DEGENERATION OF FLIGHT MUSCLE IN THE COLORADO
      POTATO BEETLE, LEPTINOTARSA DECEMLINEATA SAY (COLEOPTERA).
AB  - In the hibernating (diapausing) Colorado potato beetle, Leptinotarsa decemlineata
      Say, the flight muscles show pronounced degeneration. The muscle fibrils are
      greatly reduced in diameter and the sarcosomes are virtually absent. Similar
      signs of degeneration could be produced by extirpation of the postcerebral
      complex of endocrine glands, the corpora cardiaca and corpora allata.
      Reimplantation of active postcerebral complexes resulted in a very rapid
      regeneration of the muscle fibrils and new formation of sarcosomes.

PMID- 19866637
TI  - THE DEGENERATION AND REAPPEARANCE OF MITOCHONDRIA IN THE EGG CELLS OF A PLANT.
AB  - Details are given of the elimination of mitochondria which occurs during the
      first 1 to 2 hours of the life of the egg of the fern Pteridium aquilinum (L.)
      Kuhn. During this phase the only mitochondria present are swollen and appear
      degenerate, but subsequently the cytoplasm of the egg becomes filled with large
      mitochondria containing numerous villi. Accompanying the appearance of these
      mitochondria, many, if not all of which have a peculiar umbo-like form, is the
      production by the nucleus of conspicuous and complex evaginations. The umbo
      mitochondria are believed to be new, and a mechanism is suggested by which they
      may be generated from the complex evaginations of the nucleus.

PMID- 19866638
TI  - ON A CRYSTAL-CONTAINING BODY IN CELLS OF THE OAT COLEOPTILE.

PMID- 19866639
TI  - CONTRACTION IN GLYCERINATED MYOFIBRILS OF AN INSECT (ORTHOPTERA, ACRIDIDAE).
AB  - The A substance of glycerol-treated myofibrils of the femoral muscles of the
      locust Gastrimargus musicus (Fabr.), removed by a salt solution of high ionic
      strength, has the properties of actomyosin. A phase contrast study of these
      fibrils, contracted by the addition of ATP, has revealed that the A bands of most
      myofibrils shorten during contraction. Changes in density within the A band lead
      to the formation of C(m) and C(z) bands while I bands are still present. The A
      band region between the contraction bands is of much lower density than it is in
      the uncontracted fibril. During contraction in some fibrils the I bands
      disappeared and the A bands remained unchanged in length until contraction bands
      appeared. These results have been interpreted in terms of coiling and stretching
      of the thick filaments of the sarcomere.

PMID- 19866640
TI  - EVIDENCE For THE CYTOPLASMIC SYNTHESIS OF NUCLEAR HISTONE DURING SPERMIOGENESIS
      IN THE GRASSHOPPER CHORTOPHAGA VIRIDIFASCIATA (DE GEER).
AB  - Histone synthesis during spermiogenesis in the grasshopper Chortophaga
      viridifasciata was studied using autoradiographic and cytochemical methods. It
      was found that meiosis is followed by a cessation of RNA synthesis, an
      elimination of RNA from the nucleus, and, during the cytoplasmic sloughing
      accompanying the initial cytoplasmic elongation, a loss of most of the RNA from
      the cell. The initial phase of cell elongation results in a long spermatid headed
      by a spherical RNA-less nucleus bounded by a thin RNA-containing layer of
      cytoplasm. Subsequent nuclear elongation is accompanied by a replacement of the
      typical histones by others rich in arginine. This replacement is the result of
      synthesis of new protein. Incorporation of arginine is first seen to occur in the
      thin cytoplasmic layer surrounding the nucleus. This layer was shown by staining
      and electron microscopy to contain aggregations of ribosome-like particles. These
      observations support the conclusion that the histone is synthesized in
      association with the RNA granules in the cytoplasm, then migrates into the
      nucleus where it combines with the DNA.

PMID- 19866641
TI  - EARLY STAGES IN THE DEVELOPMENT OF PLASTID FINE STRUCTURE IN RED AND FAR-RED
      LIGHT.
AB  - Developmental changes in fine structure were studied in plastids of etiolated
      bean leaves during the time required for the protochlorophyllide-chlorophyllide
      transformation and the following lag phase prior to chlorophyll accumulation. In
      agreement with some other workers, two distinct stages of change in the fine
      structure of proplastids were found to occur upon illumination during this
      period. The first involves a dissociation of the previously fused units in the
      prolamellar bodies of the proplastids and occurs simultaneously with the
      protochlorophyllide-chlorophyllide conversion in light of 655 mmicro, but not of
      682, 700, or 730 mmicro. The effect of the red light could not be reversed by a
      simultaneously supplied stronger far-red irradiation. The energy requirements for
      these structural changes parallel those for the pigment conversion. During the
      following step the vesicles which arose from the fused units of the prolamellar
      body were dispersed in rows through the stroma, and the prolamellar bodies
      themselves disappeared. For these changes to occur, higher light energies were
      required and the leaves had to be illuminated for longer periods. A red
      preillumination seemed to accelerate the development somewhat. The structural
      changes could be induced by light of 655 mmicro, but also, to a lesser degree, of
      730 mmicro. No measurable additional chlorophyll accumulated during this period.
      Thus, the structural changes observed were independent of major changes in
      pigment content.

PMID- 19866642
TI  - FINE STRUCTURAL CHANGES IN PROPLASTIDS DURING PHOTODESTRUCTION OF PIGMENTS.
AB  - Etiolated bean leaves supplied delta-amino-levulinic acid in the dark synthesize
      large amounts of protochlorophyllide which is not converted to chlorophyllide
      upon illumination of the leaves. The fine structure of the proplastids is not
      affected by the treatment. When leaves containing "inactive" protochlorophyllide
      are exposed to light of 700 ft-c for 3 hours, they lose practically all their
      green pigments. During this period large stacks of closed membrane structures are
      built up in the region of the prolamellar body. These lamellar structures remain
      even when no or only traces of pigment are left in the leaves. In untreated
      control leaves the pigment content remained constant during similar illumination
      and the structural changes in the plastids consisted of a rearrangement of the
      vesicles from the prolamellar bodies into strands dispersed through the stroma;
      lamellae and grana formation occurred later.

PMID- 19866643
TI  - THE FINE STRUCTURE AND DEVELOPMENT OF THE COMPANION CELL OF THE PHLOEM OF ACER
      PSEUDOPLATANUS.
AB  - At maturity the companion cell of the phloem of the sycamore Acer pseudoplatanus
      has a large nucleus, simple plastids closely sheathed with rough endoplasmic
      reticulum, and numerous mitochondria. The cytoplasm contains numerous ribosomes,
      resulting in a very electron-opaque cytoplasm after permanganate fixation. Bodies
      similar to the spherosomes of Frey-Wyssling et al. (4) are collected in clusters
      and these also contain bodies of an unidentified nature similar to those found by
      Buttrose (1) in the aleurone cells of the wheat grain. The pores through the wall
      between the companion cell and sieve tube are complex and develop from a single
      plasmodesma. Eight to fifteen plasmodesmata on the companion cell side
      communicate individually with a cavity in the centre of the wall which is linked
      to the sieve tube by a single pore about twice the diameter of an individual
      plasmodesma. This pore is lined with material of an electron opacity equivalent
      to that of material bounding the sieve plate pores. The development of the cell
      organelles, the possible role played in the phloem tissue by the companion cell,
      and the function of the complex pores contained in its wall are discussed.

PMID- 19866644
TI  - THE MECHANISM OF 5-AMINOURACIL-INDUCED SYNCHRONY OF CELL DIVISION IN VI CIA FABA
      ROOT MERISTEMS.
AB  - Cessation of mitosis was brought about in Vicia faba roots incubated for 24 hours
      in the thymine analogue, 5-aminouracil. Recovery of mitotic activity began 8
      hours after removal from 5-aminouracil and reached a peak at 15 hours. If
      colchicine was added 4 hours before the peak of mitoses, up to 80 per cent of all
      cells accumulated in mitotic division stages. By use of single and double
      labeling techniques, it was shown that synchrony of cell divisions resulted from
      depression in the rate of DNA synthesis by 5-aminouracil, which brought about an
      accumulation of cells in the S phase of the cell cycle. Treatment with 5
      aminouracil may have also caused a delay in the rate of exit of cells from the
      G(2) period. It appeared to have no effect on the duration of the G(1) period.
      When roots were removed from 5-aminouracil, DNA synthesis resumed in all cells in
      the S phase. Although thymidine antagonized the effects of 5-aminouracil, an
      exogenous supply of it was not necessary for the resumption of DNA synthesis, as
      shown by incorporation studies with tritiated deoxycytidine.

PMID- 19866645
TI  - THE FINE STRUCTURE OF DIFFERENTIATING XYLEM ELEMENTS.
AB  - Differentiating xylem elements of Avena coleoptiles have been examined by light
      and electron microscopy. Fixation in 2 per cent phosphate-buffered osmium
      tetroxide and in 6 per cent glutaraldehyde, followed by 2 per cent osmium
      tetroxide, revealed details of the cell wall and cytoplasmic fine structure. The
      localized secondary wall thickening identified the xylem elements and indicated
      their state of differentiation. These differentiating xylem elements have dense
      cytoplasmic contents in which the dictyosomes and elements of rough endoplasmic
      reticulum are especially numerous. Vesicles are associated with the dictyosomes
      and are found throughout the cytoplasm. In many cases, these vesicles have
      electron-opaque contents. "Microtubules" are abundant in the peripheral cytoplasm
      and are always associated with the secondary wall thickenings. These microtubules
      are oriented in a direction parallel to the microfibrillar direction of the
      thickenings. Other tubules are frequently found between the cell wall and the
      plasma membrane. Our results support the view that the morphological association
      of the "microtubules" with developing cell wall thickenings may have a functional
      significance, especially with respect to the orientation of the microfibrils.
      Dictyosomes and endoplasmic reticulum may have a function in some way connected
      with the synthetic mechanism of cell wall deposition.

PMID- 19866646
TI  - INTRANUCLEAR AND CYTOPLASMIC ANNULATE LAMELLAE IN TUNICATE OOCYTES.
AB  - Electron microscope studies were made on various tunicate oocytes at different
      stages of growth and development. Both the inner and outer lamellae of the
      perforated nuclear envelope demonstrate considerable blebbing activity. The blebs
      of the inner lamella detach into the nucleoplasm where they undergo a special
      type of fusion process resulting in the formation of numerous, usually single,
      differentiated annulate lamellae of various lengths. The blebbing of the outer
      layer of the nuclear envelope contributes to the vesicular and granular
      endoplasmic reticulum characteristically present in the ooplasm and perhaps to
      the differentiation of cytoplasmic annulate lamellae as well. Cytoplasmic stacks
      of annulate lamellae frequently have ribosomes associated with them. In addition,
      granular accumulations are sometimes observed around or between the annuli. The
      morphological evidence suggests that, at least in many cases, the annuli in the
      annulate lamellae are patent.

PMID- 19866647
TI  - MULTIPERFORATE SEPTATIONS, WORONIN BODIES, AND SEPTAL PLUGS IN FUSARIUM.

PMID- 19866648
TI  - MITOCHONDRIAL PARTICLES SEEN IN SECTIONS.

PMID- 19866649
TI  - AN INTERCISTERNAL STRUCTURE IN THE GOLGI APPARATUS.

PMID- 19866650
TI  - IONIC EFFECTS ON LIGNIFICATION AND PEROXIDASE IN TISSUE CULTURES.
AB  - Crown-gall tumor tissue cultures release peroxidase into the medium in response
      to the concentration of specific ions in the medium. This release is not due to
      diffusion from cut surfaces or injured cells. Calcium, magnesium, and ammonium
      were, in that order, most effective in increasing peroxidase release. The enzyme
      was demonstrated cytochemically on the cell walls and in the cytoplasm. Cell wall
      fractions, exhaustively washed in buffer, still contained bound peroxidase. This
      bound peroxidase could be released by treating the wall fractions with certain
      divalent cations or ammonium. The order of effectiveness for removing the enzyme
      from the washed cell walls is: Ca(++) approximately Sr(++) > Ba(++) > Mg(++) >
      NH(4) (+). These data support the thesis presented that specific ions can control
      the deposition of lignin on cell walls by affecting the peroxidase levels on
      these walls.

PMID- 19866652
TI  - CONTRIBUTIONS TO THE KNOWLEDGE OF THE CELL AND ITS VITAL PROCESSES.

PMID- 19866651
TI  - NON-RANDOM NUCLEAR ORIENTATION DURING DNA SYNTHESIS IN TRADESCANTIA POLLEN
      GRAINS.

PMID- 19866653
TI  - ARTIFACTUAL LOCALIZATION OF FERRITIN IN THE CILIARY EPITHELIUM IN VITRO.
AB  - The accumulation of ferritin by the ciliary epithelium of the adult albino rabbit
      has been studied by electron microscopy. The experiments have been carried out
      under in vitro conditions, such that any uptake observed should be the result of
      passive diffusion of the tracerparticles rather than the product of active
      metabolic processes. The cells were fixed in osmium tetroxide and embedded in
      Araldite. Ferritin was found localized in three areas: in rows of apparent
      vesicles, free in the cytoplasmic matrix, and in the basement membrane. Some of
      the conclusions reached are as follows. The appearance of tracer in rows of
      vesicles is not in itself an adequate demonstration of pinocytosis. The
      permeability of the plasma membrane is drastically increased by osmium tetroxide
      fixation, so that tracer particles are free to diffuse across the membrane and
      wander through the cytoplasm. These results indicate the serious danger of being
      misled by artifacts when colloidal particles are used as tracers.

PMID- 19866654
TI  - LOCALIZATION OF ADENOSINE TRIPHOSPHATASE ACTIVITY IN THE RAT SPERM TAIL AS
      REVEALED BY ELECTRON MICROSCOPY.
AB  - The epididymides of rat testis were fixed in glutaraldehyde and cut as frozen
      sections. The sections were incubated in lead nitrate solution containing as a
      substrate either ATP, AMP, creatinine phosphate, beta glycerophosphate, or phenyl
      phosphate. Then they were postfixed in osmium tetroxide, embedded, sectioned, and
      examined with the electron microscope. In the sperm tail, when ATP is used as a
      substrate the reaction product (lead phosphate) is observed both in the tail
      filament complex and on the surface membrane of the mitochondrial helix of the
      middle piece. In the tail filament complex, this product is seen near the nine
      paired peripheral and two central filaments, and in the matrix between the outer
      coarse fibers. But the product is not observed within these filaments and fibers.
      In longitudinal sections, no periodicity of the deposits in the complex is
      observed. When the other phosphate compounds are used as substrates the reaction
      products appear on the surface membrane of the mitochondrial helix, and are not
      found in the tail filament complex. No distinctly different localization of the
      reaction products is observed when substrates other than ATP are used. Possible
      relationships between the structure and the function of the sperm tail are
      discussed in the light of these findings.

PMID- 19866656
TI  - GLYCOLYSIS IN RAT PERITONEAL MAST CELLS.
AB  - Glycolytic activity of rat peritoneal mast cells has been measured by the
      Cartesian ampulla diver technique. The rates of anaerobic glycolysis, expressed
      as CO(2) expelled from a bicarbonate medium, are 1.70 x 10(-6) microl and 1.43 x
      10(-6) microl per cell per hour with and without glucose, respectively. The
      aerobic glycolysis rate in the presence of glucose, assuming the respiratory
      quotient to be 1, is 0.93 x 10(-6) microl CO(2) per cell per hour. It is pointed
      out that the anaerobic and non-respiratory aerobic carbon dioxide production by
      mast cells is much higher than the respiratory oxygen uptake reported previously.
      These values have been interpreted in terms of glucose utilization.

PMID- 19866655
TI  - RESPIRATION OF RAT PERITONEAL MAST CELLS.
AB  - Methods for microgasometry of a few hundred mast cells are described. The
      Cartesian ampulla diver technique is used. The sample size is determined by
      counting the cells within the diver. The respiration rates at 37 degrees C,
      expressed in microliters per cell per hour, are 0.29 x 10(-6) without substrate
      and 0.47 x 10(-6) with glucose.

PMID- 19866657
TI  - ANALYSIS OF MUSCLE CONTRACTION BY ULTRAVIOLET MICROBEAM DISRUPTION OF SARCOMERE
      STRUCTURE.
AB  - In an effort to differentiate between the sliding filament theory for muscle
      contraction and alternative views which propose attachment between actin and
      myosin filaments at or across the H zone, rabbit psoas myofibrils were irradiated
      in various areas of the sarcomere with an ultraviolet microbeam. Irradiation of
      the I band appears to destroy the actin filaments; in vitro irradiation of F
      actin causes an irreversible depolymerization of the protein. Irradiation of the
      A band disorients the myosin but causes no apparent loss of dry mass. These
      effects are maximal at the wavelength of maximum absorption of the proteins
      involved. Actin filaments, released at the Z line of a sarcomere, are seen to
      slide into the A band on addition of ATP. Irradiation of a full A band prevents
      contraction, whereas irradiation of two-thirds of the A band, leaving a lateral
      edge intact, permits contraction at the non-irradiated edge. Thus contraction can
      occur in what is in essence only one-third of a sarcomere, eliminating any
      necessity for postulated H zone connections. These observations are in complete
      accord with the classical sliding filament theory but incompatible with either
      the contralateral filament hypothesis or the actin folding model for muscle
      contraction.

PMID- 19866658
TI  - THE FINE STRUCTURE OF ASTROCYTES IN THE CEREBRAL CORTEX AND THEIR RESPONSE TO
      FOCAL INJURY PRODUCED BY HEAVY IONIZING PARTICLES.
AB  - Normal and reactive astrocytes in the cerebral cortex of the rat have been
      studied with the electron microscope following focal alpha particle irradiation.
      The presence of glycogen and approximately 60-A fibrils identify astrocyte
      cytoplasm in formalin-perfused tissue. The glycogen particles facilitate the
      identification of small processes and subpial and perivascular end-feet. Both
      protoplasmic and fibrous astrocytes contain cytoplasmic fibrils and should be
      distinguished on the basis of the configuration of their processes and their
      distribution. Acutely reactive astrocytes are characterized by a marked increase
      in the number of glycogen granules and mitochondria from the first day after
      irradiation. These cells later hypertrophy and accumulate lipid bodies and
      increased numbers of cytoplasmic fibrils. The glial "scar" consists of a greatly
      expanded volume of astrocyte cytoplasm filled with fibrils and displays no signs
      of astrocyte death, reversion to primitive forms, or extensive multiplication.

PMID- 19866659
TI  - THE ASSOCIATION OF ACETYLCHOLINESTERASE AND MEMBRANE IN SUBCELLULAR FRACTIONS OF
      THE ELECTRIC TISSUE OF ELECTROPHORUS.
AB  - Subcellular fractions of the electric tissue of the main organ of the eel
      Electrophorus electricus were prepared in sucrose media by differential
      centrifugation and differential discontinuous gradient centrifugation. The
      distributions of acetylcholinesterase, cytochrome oxidase, DNA, and protein were
      determined. The appearance of the fractions was determined by phase contrast
      microscopy and by electron microscopy. A fraction prepared by differectial
      centrifugation at 30,000 g for 20 minutes in 0.89 M sucrose contained 63 per cent
      of the total acetylcholinesterase activity at 4 times the specific activity of
      that of the tissue homogenate. A subfraction prepared by centrifugation in a
      discontinuous density gradient showed a peak of total and relative specific
      acetylcholinesterase activity of 35 per cent and 1.9, respectively. The average
      over-all purification was 7 times. The acetylcholinesterase peak was below the
      cytochrome oxidase peak and above the DNA peak in the density gradient. The
      presence of acetylcholinesterase in the fractions was correlated with the
      presence of large fragments of the cell membrane; however, the presence of other
      tissue components was noted. The acetylcholinesterase associated with membrane
      was found to be activated by incubation with sodium deoxycholate. The possible
      use of the peak fraction containing membranes rich in acetylcholinesterase for
      the investigation of other components of the acetylcholine system and of other
      properties of the membrane is discussed.

PMID- 19866660
TI  - H-THYMIDINE DERIVATIVE POOLS IN RELATION TO MACRONUCLEAR DNA SYNTHESIS IN
      TETRAHYMENA PYRIFORMIS.
AB  - The formation of a soluble H(3)-thymidine derivative pool has been examined in
      Tetrahymena pyriformis as a function of macronuclear DNA synthesis during the
      cell life cycle. An autoradiographic technique which allows the detection of
      water-soluble materials within a cell has shown that these cells do not take up
      and retain exogenous H(3)-thymidine during G1 or G2. Uptake of H(3)-thymidine is
      restricted to the S period of the cell cycle. Additional autoradiographic
      experiments show, however, that a soluble pool of H(3)-thymidine derivatives
      persists from the end of one DNA synthesis period to the beginning of the next
      synthesis period in the subsequent cell cycle. Since this persisting pool cannot
      be labeled with H(3)-thymidine, the pool does not turn over during non-S periods.

PMID- 19866661
TI  - INTRAPOPULATION KINETICS OF THE MITOTIC CYCLE.
AB  - Data obtained with time lapse cinemicrographic techniques showed that the
      distribution of generation times for exponentially proliferating human amnion
      cells in culture is skewed to the right and that reciprocals of generation times
      appear normally distributed. As shown for bacteria, the true age distribution is
      much broader than theoretical distributions which fail to take into account the
      dispersion of generation times. By means of the technique utilizing
      autoradiographic detection of tritiated thymidine in cells whose mitotic
      histories were recorded by time lapse cinemicrography, it was shown that the G1
      distribution is similar to the generation time distribution but is more variable.
      In our experiments, the G2 + prophase distribution resembled the generation time
      and G1 distributions. The data suggested two possibilities for S: either it is
      relatively constant, or it is inversely related to the lengths of G1 and G2 +
      prophase. Since G1 is more variable than the total cycle, and G2 + prophase more
      variable than the computed sum of S + G2 + prophase + metaphase, it was concluded
      that the relationships between parts of the cycle are non-random and that
      compensating mechanisms apparently help regulate the lengths of successive parts
      of the mitotic cycle in individual cells.

PMID- 19866662
TI  - AUTORADIOGRAPHIC STUDY OF SUGAR AND AMINO ACID ABSORPTION BY EVERTED SACS OF
      HAMSTER INTESTINE.
AB  - Autoradiographs were prepared from frozen sections of everted sacs of hamster
      jejunum which had been incubated in vitro with C(14)- or H(3)-labeled sugars and
      amino acids. When such tissue was incubated in 1 mM solutions of L-valine or L
      methionine, columnar absorptive cells at tips of villi accumulated these amino
      acids to concentrations ranging from 5 to 50 millimoles per liter of cells.
      Quantitative data were obtained by microdensitometry of C(14) autoradiographs.
      Similar, though less striking, results were obtained with the sugars: galactose,
      3-0-methylglucose, alpha-methylglucoside, and 6-deoxyglucose. In all cases the
      marked "step-up" in concentration occurred near the brush border of the cell, and
      a "step-down" in concentration occurred at the basal pole of the cell. Known
      inhibitors of intestinal absorption, e.g., phlorizin in the case of sugars,
      blocked the concentrative step at the luminal border of the absorptive cell. It
      is inferred from these data that active transport systems for sugars and amino
      acids reside in the brush border region of the cell. Additional evidence suggests
      that the basal membrane of the cell may be the site of both a diffusion barrier
      and a weak transport system directed into the cell.

PMID- 19866663
TI  - SYNTHESIS OF CELLULOSE BY ACETOBACTER XYLINUM: VIII. On the Formation and
      Orientation of Bacterial Cellulose Fibrils in the Presence of Acidic
      Polysaccharides.
AB  - The transfer of the glucosyl moiety from uridine diphosphate glucose in the
      presence of Acetobacter xylinum cell-free extracts led to the formation of a
      mixture of alkali-soluble and -insoluble cellodextrins. Typical cellulose fibrils
      could not be detected by electron microscopy in this product. Immediately after
      release into the medium, cellulose formed by whole cells is in a "prefibrous"
      form which passes through Millipore filters of 0.45 and 0.8 micro pore diameter.
      Non-filtrable fibrils arise from this material probably by a process of
      crystallization involving no extracellular enzymes. Fibrils formed in shaken cell
      suspensions intertwine and form aggregates visible to the naked eye. In quiet
      suspensions pellicles are formed which float on the surface. Soluble Na
      carboxymethylcellulose (CMC) is incorporated into cellulose fibrils formed in its
      presence, probably by a process of co-crystallization. Aggregation of fibrils
      containing CMC is delayed because of electrostatic repulsion between carboxylic
      groups. The aggregation time depends on the amount of CMC incorporated, its
      degree of substitution, the pH of the medium, and the ionic strength. The amount
      of CMC incorporated depends on the relative concentration CMC/cellulose and on
      the similarity of the CMC and the cellulose molecules i.e. in molecular weight
      and the number of carboxyl substitutions. Cellulose pellicles formed in the
      presence of CMC by unshaken cell suspensions consist of crossed, superimposed
      layers of parallel oriented cellulose fibrils. The same phenomenon is observed
      when phosphomannan, but not levan, is substituted for CMC. The biogenesis of
      oriented cellulose fibrils is envisaged as a process comprising the following
      steps: polymerization of the monomeric precursor, diffusion of the molecule to
      crystallization sites, crystallization, and orientation. It is proposed that
      charged polysaccharides play a role similar to that of CMC in affecting the
      orientation of cellulose fibrils in the plant cell wall.

PMID- 19866664
TI  - THE ULTRASTRUCTURE OF COTYLEDONARY TISSUE FROM GOSSYPIUM HIRSUTUM L. SEEDS.
AB  - Quiescent cottonseeds stored in a dry, anaerobic situation for over a year have
      been shown to contain cells whose contents are ultrastructurally similar to those
      of normal, fully hydrated plant cells. Plastids, mitochondria, and nuclei of the
      cells of cotyledon tissue in dry seeds possess normal-looking double membranes
      even under conditions of extreme desiccation. Previous reports have indicated on
      the basis of light microscopic work, that the cells of certain dry seeds do not
      possess nuclear membranes or mitochondria. The cells of the dry cottonseed do
      contain these structures, however. Dictyosomes have not been observed in the
      spongy parenchymal cells of the cotyledon tissue; it is suggested that they are
      concerned with translocation and/or utilization of material. The storage
      materials in the cells, protein and oil, are contained in vacuolar areas enclosed
      by a single membrane.

PMID- 19866665
TI  - OLFACTORY CILIA IN THE FROG.
AB  - Olfactory epithelium from the frog was examined in the living state by light
      microscopy and in the fixed state by electron microscopy. Particular attention
      was paid to the layer of cilia and mucus which covers the surface of the
      epithelium. The olfactory cilia differed from typical cilia in that they (a)
      arose from bipolar neurons and had centrioles near their basal bodies, (b) were
      up to 200 microns in length, of which the greater part was a distal segment
      containing an atypical array of ciliary fibers, (c) were often immotile, (d) had
      their distal segments arranged in parallel rows near the surface of the mucus,
      and (e) had many vesicles along their shafts and had splits in the array of
      fibers in their distal segments. These specializations make the olfactory cilia
      similar to cilia found on other sensory cells and support the theory that they
      are the locus where electrical excitation in the olfactory organ is initiated by
      contact with odorous substances.

PMID- 19866666
TI  - STUDIES ON THE INTRACELLULAR DIGESTIVE PROCESS IN MAMMALIAN TISSUE CULTURE CELLS.
AB  - DNA-protein coacervates containing colloidal gold particles were readily
      phagocytized by strain L fibroblasts. During the subsequent digestion process,
      the gold particles served as markers which permitted the demonstration of the
      evolution of digestive vacuoles to multivesicular bodies and finally to dense
      bodies. Acid phosphatase and esterolytic activity was present in these
      structures. The hydrolytic enzymes were apparently brought to the phagocytotic
      vacuoles in small vesicles originating in the Golgi region. These vesicles
      entered the vacuoles prior to the digestion of the coacervates and the appearance
      of positive cytochemical reactions. The cytoplasmic dense bodies frequently
      merged with the phagocytotic vacuoles. This was demonstrated by prelabeling the
      dense bodies with colloidal iron prior to phagocytosis of the coacervates. In
      addition, evidence is presented for the interrelationship of the phagocytotic and
      autophagic pathways.

PMID- 19866667
TI  - DISTRIBUTION OF TRITIUM-LABELED DNA AMONG CHROMOSOMES DURING MEIOSIS : I.
      Spermatogenesis in the Grasshopper.
AB  - Thymidine-H(3) of high specific activity was used to study the distribution of
      labeled chromatids during meiotic divisions in spermatocytes of a species of
      grasshopper (Orthoptera). The distribution is regularly semiconservative as has
      been shown previously for mitosis, i.e., all chromatids are labeled after
      incorporation of thymidine-H(3) into DNA at premeiotic interphase. If
      incorporation occurs at the interphase preceding this one, the chromosomes arrive
      at meiotic divisions with the equivalent of one chromatid of each homologue
      labeled. Chromatid exchanges occur at a frequency which is very nearly that
      predicted on the assumption that each chiasma represents an exchange between
      homologous chromatids. However, the exchanges are randomly distributed among
      chromosomes in a size group, whereas chiasmata are not. A quantitative analysis
      of the frequency and pattern of exchanges indicates that most of these result
      from breakage and reciprocal exchange between homologous chromatids. Sister
      chromatid exchanges are much less frequent and may be limited to premeiotic
      stages.

PMID- 19866668
TI  - MORPHOLOGICAL AND BIOCHEMICAL CORRELATES OF CEREBRAL MICROSOMES : I. Isolation
      and Chemical Characterization.
AB  - Microsomal fractions, both homogeneous in appearance and functionally operative,
      were isolated from a homogenate of rat cerebral cortex by fractionation in water.
      The preparations thus obtained contain the membranous elements of the endoplasmic
      reticulum, synaptic vesicles, and ribosomes. Esterase, ATPase, and glutamine
      synthetase were found to be present and fully functional in the microsomal
      fractions isolated in water. The contamination of the water-isolated microsomal
      fractions by mitochondria and lysosomes was found to be considerably lower than
      in microsomal pellets isolated in sucrose. The contamination by nerve ending
      particles, as judged by electron microscopy and by the levels of soluble lactic
      dehydrogenase entrapped in the cytoplasm of the particles, was also low. Most of
      the contamination by mitochondria and nerve ending particles could be removed by
      treatment of the microsomal pellet with 150 mM NaCl. Resistant to elution by this
      treatment is the lysosomal contamination as well as microsomal esterase and
      ATPase. Glutamine synthetase, on the other hand, was almost totally solubilized.
      Microsomal preparations isolated in water are also shown to contain amounts of
      protein, RNA, phospholipid, and ganglioside comparable to those found in
      microsomal preparations isolated in sucrose.

PMID- 19866669
TI  - MORPHOLOGY OF GAMETE MEMBRANE FUSION AND OF SPERM ENTRY INTO OOCYTES OF THE SEA
      URCHIN.
AB  - Sea urchin gametes predominate in molecular studies of fertilization, yet
      relatively little is known of the subcellular aspects of sperm entry in this
      group. Accordingly, it seemed desirable to make a detailed examination of sperm
      entry phenomena in sea urchins with the electron microscope. Gametes of the sea
      urchins Arbacia punctulata and Lytechinus variegatus were used in this study.
      Samples of eggs containing 2 to 8 per cent oocytes were selected and fixed with
      osmium tetroxide in sea water at various intervals after insemination. Fixed
      specimens were embedded in Epon 812, sectioned, and examined with an electron
      microscope. An apical vesicle was observed at the anterior end of the acrosome.
      The presence of this structure, together with other observations, suggested that
      initiation of the acrosome reaction in sea urchin sperm involves dehiscence of
      the acrosomal region with the subsequent release of the acrosomal granule.
      Contact and initial fusion of gamete membranes was observed in mature eggs and
      oocytes and invariably involved the extended acrosomal tubule of the
      spermatozoon. Only one spermatozoon normally enters the mature egg. The
      probability of locating such a sperm in ultrathin sections is exceedingly low.
      Several sperm do normally enter oocytes. Consequently, observations of sperm
      entry were primarily restricted to the latter. The manner of sperm entry into
      oocytes did not resemble phagocytosis. Organelles of the spermatozoon were
      progressively divested of their plasma membrane as they entered the ground
      cytoplasm of the oocyte fertilization cone. Initiation of the acrosome reaction,
      contact and initial fusion of gamete membranes, and sperm entry into oocytes of
      sea urchins conform to the Hydroides-Saccoglossus pattern of early fertilization
      events as described by Colwin and Colwin (13).

PMID- 19866670
TI  - MACROMOLECULAR EVENTS LEADING TO CELL DIVISION IN TETRAHYMENA PYRIFORMIS AFTER
      REMOVAL AND REPLACEMENT OF REQUIRED PYRIMIDINES.
AB  - Tetrahymena pyriformis were brought to a non-growing state by removal of
      pyrimidines from their growth medium. During pyrimidine deprivation cell number
      increased 3- to 4 fold, and this increase was accompanied by one or more complete
      cycles of macronuclear DNA replication. Autoradiographic studies show that
      endogenous protein and RNA were turning over throughout starvation and that RNA
      breakdown products were used to support the DNA synthesis that occurred during
      the early period of starvation. However, after 72 hours of starvation all DNA
      synthesis and cell division had ceased. Feulgen microspectrophotometry shows the
      macronuclei of these cells to have been stopped at a point prior to DNA
      replication (G1 stage). After pyrimidine replacement the incorporation of H(3)
      uridine, H(3)-adenosine, and H(3)-leucine was measured by the autoradiographic
      grain counting method. The results indicate that RNA synthesis began to increase
      almost immediately, but that there was a lag of almost an hour before an increase
      in protein synthesis. In agreement with the autoradiographic data, chemical data
      also show that cellular content of RNA began to increase shortly after pyrimidine
      replacement but that cellular protein content did not increase until about one
      hour later. Pulse labeling of the cells with H(3)-thymidine at intervals after
      pyrimidine replacement shows that labeled macronuclei first began to appear at
      150 minutes; that 98 per cent of the macronuclei were in DNA synthesis at 240 to
      270 minutes; and that the percentage then began to decrease from 300 to 390
      minutes, at which time only 25 per cent of the macronuclei were labeled. Cellular
      content of DNA did not increase for at least 135 minutes after pyrimidine
      replacement; however, just before the first cells divided (360 minutes) the DNA
      content had doubled. After pyrimidine replacement the cells first began to divide
      at 360 minutes, and 50 per cent had divided at 420 minutes; however, all cells
      had not divided until 573 minutes. This technique of chemical synchronization of
      cells in mass cultures makes feasible detailed biochemical analysis of events
      leading to nuclear DNA replication and cell division.

PMID- 19866671
TI  - STUDIES ON THE ORGANIZATION OF THE BRUSH BORDER IN INTESTINAL EPITHELIAL CELLS :
      I. Tris Disruption of Isolated Hamster Brush Borders and Density Gradient
      Separation of Fractions.
AB  - Brush borders isolated from the epithelial cells of hamster jejunum have been
      dissociated by treatment with 1 M Tris(hydroxymethyl)aminomethane into several
      subfractions which can be separated by means of centrifugation on glycerol
      density gradients. Investigation of the chemical specificity of disrupting agents
      suggests that the amino group of Tris, in its positively charged state, is
      involved. Five individual bands or fractions have been routinely recovered from
      density gradients. The distribution of alkaline phosphatase and maltase
      activities among these fractions has been studied and the results indicate that
      both enzymes are predominantly associated with one fraction which has been
      identified in a companion paper as being composed of the membranes of the brush
      border microvilli. A fibrillar material of unidentified origin has also been
      obtained from Tris-disrupted brush borders.

PMID- 19866672
TI  - STUDIES ON THE ORGANIZATION OF THE BRUSH BORDER IN INTESTINAL EPITHELIAL CELLS :
      II. Fine Structure of Fractions of Tris-Disrupted Hamster Brush Borders.
AB  - Two of the fractions obtained by density gradient centrifugation of Tris
      disrupted brush borders from hamster intestinal mucosa have been identified as
      the microvillus cores and their surrounding membranous coats, respectively. This
      identification has the following morphological basis. In shadowed preparations
      one fraction (cores) appears as rounded, compact rods, and the other fraction
      (coats) appears as flattened sheets. Both rods and sheets have dimensions
      appropriate to the identities assigned to them. In addition, negative staining
      shows that the rods are composed of aligned particles of roughly 60 A, consistent
      with the appearance of the core in tissue section, where 60-A fibrils are
      characteristic. The sheets are covered by non-aligned particles of approximately
      the same size. Sectioned preparations show that the core fraction contains
      predominantly fibrous material with some membranous contamination and that the
      coat fraction is apparently composed exclusively of elongated sacs with a unit
      membrane structure. Some details of the structure of the core are evident in
      cases where the compact rod appears to be loosened, revealing a doubled strand.
      The strand is approximately 350 A wide; the compact rod is roughly twice this
      width. With negative staining the strand shows a dense central region. The
      morphological identification presented here is consistent with the distribution
      of enzymic activity among the density gradient fractions described in the
      preceding paper.

PMID- 19866673
TI  - AN EFFECT OF ADENOSINE TRIPHOSPHATE ON THE LIGHT SCATTERED BY SUSPENSIONS OF
      CILIA.
AB  - Cilia were isolated from Tetrahymena pyriformis by an ethanol-calcium method.
      Addition of adenosine triphosphate to a suspension of intact or digitonin
      extracted cilia caused a decrease of about 20 per cent in turbidity. Study of
      fractionated cilia showed that the presence of two distinct axonemal components,
      the outer fibers and the 30S dynein (the axonemal ATPase protein), was necessary
      for this effect on turbidity to occur. The decrease in turbidity is interpreted
      as a result of a specific interaction of ATP with these protein components
      causing an effective increase in hydration. The high nucleotide specificity
      suggests that the change in hydration is closely related to the processes
      responsible for motility. The outer fibers themselves swell when suspended in
      media of very low ionic strength. The concentration of salt needed to prevent
      this swelling (2 mM MgSO(4) or 30 mM KCl) is about the same as that needed to
      keep dynein bound to the fibers. The recombination of purified 30S dynein with
      the outer fibers can be followed by the rise in turbidity resulting from
      increased dry mass of the particles.

PMID- 19866674
TI  - ON THE MECHANISM OF DRUG HYDROXYLATION IN RAT LIVER MICROSOMES.
AB  - The TPNH- and O(2)-dependent drug hydroxylation system of liver microsomes has
      been studied using normal rats and rats in which the drug-hydroxylating activity
      has been enhanced by repeated injections of phenobarbital. The oxidative
      demethylation of aminopyrine is employed as an assay. Optimal conditions for the
      assay with regard to the concentrations of TPNH and aminopyrine are established.
      TPN inhibits the reaction in a competitive manner, similarly to its effect on the
      microsomal TPNH-cytochrome c reductase. Drug hydroxylation, but not the "TPNH
      oxidase," TPNH-cytochrome c, -2,6-dichlorophenolindophenol, or -neotetrazolium
      reductase reaction, or the TPNH-dependent lipid peroxidation, is blocked by
      carbon monoxide. Microsomes from phenobarbital-treated rats exhibit increased
      activities of the various TPNH-linked reductase reactions, parallel to the
      increased drug hydroxylation activity, whereas the "TPNH oxidase" activity does
      not change appreciably. Measurements with microsomes from drug-treated animals
      reveal a 1:1:1 stoichiometry of aminopyrine-dependent oxygen uptake, TPNH
      oxidation, and formaldehyde formation. Attempts to solubilize the drug
      hydroxylating enzyme system are also presented. It is concluded that the drug
      hydroxylating enzyme system involves the microsomal TPNH-cytochrome c reductase
      and CO-binding pigment, and a hypothetic reaction scheme accounting for the data
      presented is proposed.

PMID- 19866675
TI  - FURTHER STUDIES ON THE INDUCTION OF THE DRUG-HYDROXYLATING ENZYME SYSTEM OF LIVER
      MICROSOMES.
AB  - Further studies of the induction of the liver microsomal drug-hydroxylating
      enzyme system by pretreatment of rats with various drugs are presented. The
      phenobarbital-induced increase in the microsomal content of CO-binding pigment
      and in the activities of TPNH-cytochrome c reductase and the oxidative
      demethylation of aminopyrine is proportional, within certain limits, to the
      amount of phenobarbital injected. Removal of the inducer results in a parallel
      decrease in the levels of CO-binding pigment, TPNH-cytochrome c reductase, and
      aminopyrine demethylation. Other inducing drugs have been investigated and shown
      to act similarly to phenobarbital. The early increase in these enzymes is found
      in the microsomal subfraction consisting of rough-surfaced vesicles, whereas
      repeated administration of the inducing drug results in a concentration of the
      enzymes in the smooth-surfaced vesicles. The phenobarbital-stimulated formation
      of endoplasmic membranes is reflected in increased amounts of the various
      microsomal phospholipid fractions as revealed by thin layer chromatography. There
      is no significant difference between the stimulated rates of P(i) (32)
      incorporation into phospholipids of the two different microsomal subfractions in
      response to phenobarbital treatment. The drug-induced enzyme synthesis is
      unaffected by adrenalectomy.

PMID- 19866676
TI  - STUDIES ON CELL DEFORMABILITY : I. Effect of Surface Charge.
AB  - The deformability of the surface membranes of Sarcoma 37 and Ehrlich murine
      ascites tumor cells was assessed by the pressure required to suck a hemispherical
      bulge from these cells into a micropipette. It was shown that treatment with
      neuraminidase allowed the cells to be deformed with significantly less suction,
      and that enzymatic treatment also produced a significant reduction in surface
      charge as determined by measurement of cellular electrophoretic mobility. It is
      suggested that the increase in cellular deformability may be related to charge
      reduction, and that the charge at the cell periphery may affect not only the
      magnitude of the potential energy barriers hindering contact between cells, but
      also the ease with which cells can form low radius of curvature probes in order
      to help overcome these barriers.

PMID- 19866677
TI  - MICROSPECTROPHOTOMETRY OF CYTOCHROMES IN THE SINGLE CELL AT ROOM AND LIQUID
      NITROGEN TEMPERATURES.
AB  - By increasing further the sensitivity of microspectrophotometry, it is now
      possible to measure, under favorable conditions, the smaller absorption bands of
      the respiratory pigments of single cells in the visible region of the spectrum. A
      considerable aid in the distinction between cytochromes is afforded by liquid
      nitrogen microspectrophotometry. Under favorable conditions, the height of the
      peaks is increased over 8-fold at low temperatures. In diploid yeast,
      characteristically sharpened components not resolvable at room temperature are
      observed at low temperature; and in pentaploid yeast, a hitherto unrecognized
      pigment is observed at 583 mmicro. These preliminary results indicate the
      feasibility and the value of low temperature microspectrophotometry of biological
      materials.

PMID- 19866678
TI  - COLLAGENOLYTIC ACTIVITY IN RAT BONE CELLS : Characteristics and Intracellular
      Location.
AB  - An assay system for estimating quantitatively collagenase-like activity present
      in bone cells has been developed as part of a more general investigation of
      mechanisms of bone resorption. Methods are described for preparing from bone a
      C(14)-labeled collagen which is relatively pure and highly resistant to
      degradation by trypsin although readily broken down by bacterial collagenase.
      Collagenolytic activity in homogenates of bone cells harvested from rat
      metaphyseal bone was measured as the number of counts per minute released in
      ultrafiltrable form from the C(14)-labeled collagen substrate after 40 minutes'
      incubation at 37 degrees C and pH 7.3. Using these techniques, the presence of
      collagenase-like activity in whole bone cell homogenates was confirmed and the
      heat lability, partial cation dependence, pH optimum, and some other
      characteristics of the crude material were determined. Moreover, the major
      portion of the homogenate activity was found in a particulate fraction
      sedimenting in a centrifugal field between 700 and 15,000 g. The marked
      enhancement and solubilization of this activity by surface-active agents or
      freeze-thawing, together with the presence of considerable acid phosphatase
      activity in the same fraction and its sedimentation characteristics, suggested
      that it might be contained in lysosomes or similar bodies. The implications of
      these observations with respect to the physiology of collagen resorption in
      general and bone resorption in particular are discussed.

PMID- 19866679
TI  - LOCALIZATION OF ANTIBODIES BY ELECTRON MICROSCOPY IN DEVELOPING ANTIBODY
      PRODUCING CELLS.
AB  - The development of antibody-producing cells in the early stages of the secondary
      or hyperimmune response has been studied with the electron microscope in lymph
      nodes of adult chinchilla rabbits immunized with ferritin or apoferritin. The
      intracellular distribution of antiferritin antibodies was determined in the lymph
      node cells at 1 to 5 days after a booster injection, employing the labelling
      technique previously used by the authors (12) to demonstrate the localization of
      antibodies in mature plasma cells. Antibodies were first detected at 48 hours in
      blasts; i.e., cells which have a poorly developed endoplasmic reticulum and a
      cytoplasm filled with many ribosomes grouped in clusters. The label was
      subsequently found in forms intermediate between blasts and plasma cells
      (plasmoblasts, immature plasma cells), in which the endoplasmic reticulum
      appeared progressively more developed. Antiferritin antibodies were also found in
      cells in mitosis. In all the above cell types, antigen-antibody precipitates were
      consistently found in the perinuclear space and in the cisternae of the granular
      endoplasmic reticulum, from an early stage in the development of the latter.
      Evidence was also obtained for the presence of antibody in the Golgi area. The
      results are discussed in relation to the possible cellular sites of antibody
      synthesis.

PMID- 19866680
TI  - THE FINE STRUCTURE OF LIPOFUSCIN AGE PIGMENT IN THE NERVOUS SYSTEM OF AGED MICE.
AB  - An examination of the topographic distribution of lipofuscin pigment granules
      with the light and electron microscope revealed either smaller and randomly
      "dispersed" or larger and more complex "clustered" pigment configurations in the
      cytoplasm of neurons in the dorsal ganglia and ventral spinal cord of 24-month
      old male mice. Qualitative comparisons revealed no major differences in shape,
      size, complexity, density, orientation, and cytologic distribution of the pigment
      bodies in motor and sensory neurons. In general, when the pigment granules were
      quite numerous within the 2 types of cells, they were smaller in size (
      approximately lmicro), had a dense homogeneous matrix with few bands or lamellae,
      and were uniformly distributed throughout the cytoplasm. In contrast, when the
      pigment configurations were less in number, they were usually larger in size (
      approximately 3micro), had a more complex internal banded structure, and appeared
      more localized within the cell. Examination of the bands revealed a repeating
      pattern of approximately 70 A. The bands appeared to fuse, forming hexagonal
      arrays of linear densities intersecting at an angle of approximately 120 degrees
      in some regions of the pigment bodies. Structural similarities suggested that the
      striated membranous bands may be composed of phospholipids.

PMID- 19866681
TI  - ANTIGEN-INDUCED CHANGES IN LYMPHOID CELL HISTONES : II. Regional Lymph Nodes.
AB  - The nuclear histones of control and antigen-affected lymphocytes and thymocytes
      were measured in terms of their intensity of staining with ammoniacal-silver (A
      S) and alkaline fast green (FG). Subcutaneous injection of full strength and
      doubly concentrated tetanus toxoid into the upper forelimb was followed by an
      acute decrease in the intensity of the FG and A-S staining of the thymocyte
      nuclear histones. Such changes in staining were delayed in the nuclear histones
      of the regional axillary lymph nodes. In contrast, the injection of a 1:100
      dilution of tetanus toxoid caused an acute decrease in staining of the nuclei of
      the regional lymph node lymphocytes but only minimal changes in the thymocytes.
      An acute decrease in staining of the lymph node lymphocytes also occurred when
      heterologous serum proteins were used as the antigen. Prior administration of
      cortisone was found to inhibit the antigen-induced changes in the staining of
      lymphocyte nuclear histones. No such inhibitions occurred after the
      administration of saline solution. The findings suggest that the nuclear histones
      play a significant role in the immunological competence of lymphoid cells.
      However, additional studies are needed to define the biochemical basis of the
      observed changes as well as the mechanisms whereby antigen-induced changes in
      nuclear histones participate in the complex cellular and serological alterations
      which are evoked by antigens, viz. plasma cell formation and antibody synthesis.

PMID- 19866682
TI  - STUDIES ON CILIA : II. Examination of the Distal Region of the Ciliary Shaft and
      the Role of the Filaments in Motility.
AB  - Termination of peripheral filaments of the axoneme of gill cilia of fresh-water
      mussels (Elliptio or Anodonta) occurs in characteristic fashion: (a) subfiber b
      of certain doublets ends leaving a single simplified tubular unit; (b) the wall
      of the unit becomes thick and may even obliterate the interior; and (c) the
      filament drops out of the 9 + 2 pattern. The order in which doublets begin
      simplifying is also characteristic. This may be determined by numbering the
      filaments, those with the bridge being 5-6, with the direction of numbering
      determined by the apparent enantiomorphic configuration (I to IV) of the cross
      section. Shorter filaments can be identified in simplifying tips with mixed
      double and single peripheral units. In this material, laterofrontal cirri show a
      morphological specialization in the region where individual cilia simplify. The
      cilia studied run frontally from the body of the cirrus and point in the
      direction of effective stroke. The longest filaments (Nos. 3, 4, 5, 6, 7) appear
      as the doublets at the bottom of the cross-section, nearest the surface of the
      cell of origin. Above them, and above the central pair, a dark band (a section of
      a dense rod) runs through the matrix. The remaining filaments are the single
      units. Effective-pointing frontal and lateral ciliary tips end in a fashion
      similar to laterofrontal tips, although no dense band is present. For all
      effective-pointing tips studied, the order in which the peripheral filaments end
      appears to be Nos. (9, 1), 8, 2, 7, 6, 3, 4, 5. However, recovery-pointing
      lateral tips show a different order: Nos. 7, 6, 8, 5, 9, 4, 1 (3, 2), although
      the longer filaments are still at the bottom of the cross-section. In simple
      models of ciliary movement involving contraction of the peripheral filaments,
      filaments at the top of the cross-section should be longer, if any are. Such
      models are not supported by the evidence here. These results can be interpreted
      as supporting sliding-filament models of movement where no length change of
      peripheral filaments occurs.

PMID- 19866684
TI  - NUCLEOLAR AND BIOCHEMICAL CHANGES DURING UNBALANCED GROWTH OF TETRAHYMENA
      PYRIFORMIS.
AB  - Numerous nucleoli can be observed in the macronucleus of the logarithmically
      growing ciliated protozoan Tetrahymena pyriformis; at late log phase the nucleoli
      aggregate and fuse. In stationary phase this fusion process continues, leaving a
      very few large vacuolated nuclear fusion bodies in the nucleus. When these
      stationary phase cells are placed into fresh enriched proteose peptone medium,
      the large fusion bodies begin to disaggregate during the 2.5-hour lag phase
      before cell division is initiated. By 3 to 6 hours after inoculation the
      appearance of the nucleoli in many cells returns to what it was in logarithmic
      cells. In view of the possible role of nucleoli in ribosome synthesis, attempts
      were made to correlate the morphological changes to changes in RNA and protein
      metabolism. The beginning of an increased RNA synthesis was concomitant with the
      beginning of disaggregation of the large fusion bodies into nucleoli, which was
      noticed in some cells by 1 hour after the return to fresh enriched proteose
      peptone medium. Increased protein synthesis then followed the increased RNA
      synthesis by 1 hour. The supply of RNA precursors (essential pyrimidines) were
      removed from cultures which were grown on a chemically defined synthetic medium,
      in order to study the relation between nucleolar fusion and synthesis of RNA and
      protein. Pyrimidine deprivation drastically curtailed RNA and protein synthesis,
      but did not cause fusion of nucleoli. When pyrimidines were added back to this
      culture medium, RNA synthesis was immediately stimulated and again preceded an
      increased protein synthesis by 1 hour. These studies suggest the involvement of
      unfused nucleoli in RNA and protein synthesis and demonstrate the extreme
      plasticity of nucleoli with respect to changes in their environment.

PMID- 19866683
TI  - THE OCCURRENCE AND STRUCTURE OF MICROBODIES : A Comparative Study.
AB  - Livers from chickens, rats, mongrel dogs, Dalmatian dogs, and man have been
      examined in the electron microscope in order to compare the microbodies with the
      known content of uricase. It is concluded that microbodies with inclusion are
      present in rats, mongrel dogs, and, although the inclusion generally is smaller,
      in Dalmatian dogs. The inclusion has a characteristic structural appearance.
      These species (rat, dog) have uricase. Chickens and man lack both the enzyme
      uricase and the microbody inclusion. This evidence and that from previously
      published electron micrographs in the literature on microbodies support the
      notion of a positive correlation between uricase and microbodies with an
      inclusion. It is recommended that the term "uricosome" be used for such
      microbodies that have an inclusion of the appearance here described.

PMID- 19866685
TI  - THE STRUCTURE AND FORMATION OF PROTEIN GRANULES IN THE FAT BODY OF AN INSECT.
AB  - In the larva of the butterfly Calpodes ethlius, the fat body begins to store
      protein in the form of granules at about 30 to 35 hours before pupation, at a
      time when the endocuticle is being resorbed. At least two sorts of granule can be
      distinguished. The first granules to arise are those within vesicles of the Golgi
      complex. These may increase in size by incorporating material from microvesicles
      at their surface and by coalescence with one another. Later, at about 10 hours
      before pupation, another sort of granule arises by the isolation of regions of
      the endoplasmic reticulum (ER) within paired membranes derived from Golgi
      vesicles. Several of these ER isolation bodies coalesce, with fusion of their
      outer isolating membranes. The ribosomes and membranes may then disappear and the
      granules become indistinguishable from the protein granules formed from Golgi
      vesicles, or the ribosomes may remain and be embedded in dense crystalline
      protein, forming a storage body for both protein and RNA. Mitochondria are
      isolated within paired membranes in the same way as regions of the ER. The
      isolated mitochondria also coalesce in a similar manner. When the inner membranes
      are lost, the structure of a group of isolation bodies is indistinguishable from
      that of a cytolysome. Isolation within paired membranes, as described here, may
      be of general importance in segregating regions of massive lysis or massive
      sequestration.

PMID- 19866686
TI  - REVERSIBLE AND IRREVERSIBLE CHANGES IN THE FINE STRUCTURE OF NERVOUS TISSUE
      DURING OXYGEN AND GLUCOSE DEPRIVATION.
AB  - Rabbit retinas were fixed for electron microscopy immediately after removing the
      eye and after incubations in a control medium and in three different deprivation
      media that were identical with the control except for the omission of glucose,
      oxygen, or both. A systematic comparison was made of the electron microscopic
      appearance of the different retinas with particular attention to four regions:
      rod inner segments, rod synapses, bipolar cell bodies, and ganglion cell
      myelinated axons. Retinas fixed after 1 hour of incubation in the control medium
      appeared virtually identical with those fixed immediately after ocular removal.
      Retinas deprived of oxygen and glucose for only 3 minutes showed generalized
      swelling of mitochondria and alterations in the structure of the synapses with
      loss of synaptic vesicles. Extending the combined deprivation caused further
      mitochondrial swelling and synaptic changes and also led to progressive swelling
      of the Golgi membranes and the granular endoplasmic reticulum. All these changes
      were almost completely reversible for up to 20 minutes but were irreversible by
      30 minutes, at which time multiple discontinuities had appeared in cell and
      organelle membranes. Anoxia alone produced alterations similar to those found
      after somewhat shorter periods of the combined deprivation, whereas glucose
      withdrawal produced only minor changes. These electron microscopic results
      correlate quite well with previously reported electrophysiological measurements.

PMID- 19866687
TI  - THE FINE STRUCTURE OF TESTICULAR INTERSTITIAL CELLS IN GUINEA PIGS.
AB  - In guinea pig testes perfused with either glutaraldehyde or osmium tetroxide
      fixative, the cytoplasm of the interstitial cells contains an exceptionally
      abundant agranular endoplasmic reticulum. The reticulum in central regions of the
      cell is a network of interconnected tubules, but in extensive peripheral areas
      the reticulum is commonly organized into closely packed, flattened cisternae
      which are fenestrated. Occasional small patches of the granular reticulum occur
      in the cytoplasm and connect freely with the agranular reticulum. The
      mitochondria have a dense matrix and contain cristae and some tubules. The Golgi
      complex is disperse and shows no evidence of secretory material. The cytoplasm
      also contains lipid droplets. Lipofuscin pigment granules are probably
      polymorphic residual bodies and contain three components: (1) a dense material
      which at high magnification shows a 75-A periodicity; (2) a medium-sized lipid
      droplet; and (3) a cap-like structure. In glutaraldehyde-perfused testis the
      interstitial cell cytoplasm appears to have the same density from cell to cell,
      and the agranular reticulum is tubular or cisternal but not in the form of empty
      vesicles. Thus the "dark" and "light" cells and the vesicular agranular reticulum
      sometimes encountered in other fixations may be artifacts. Biochemical results
      from other laboratories, correlated with the present findings, indicate that the
      membranes of the agranular endoplasmic reticulum in guinea pig interstitial cells
      are the site of at least two enzymes of androgen biosynthesis, the 17-hydroxylase
      and the 17-desmolase.

PMID- 19866689
TI  - ULTRAVIOLET MICROBEAM IRRADIATION IN LIVING CELL MEMBRANES.

PMID- 19866688
TI  - ELECTRON MICROSCOPIC EXAMINATION OF THE SITES OF NUCLEAR RNA SYNTHESIS DURING
      AMPHIBIAN EMBRYOGENESIS.
AB  - The site of H(3)-uridine incorporation and the fate of labeled RNA during early
      embryo-genesis of the newt Triturus pyrrhogaster were studied with electron
      microscopic autoradiography. Isolated ectodermal and mesodermal tissues from the
      embryos were treated in H(3)-uridine for 3 hours and cultured in cold solution
      for various periods before fixation with OsO(4) and embedding in Epon. At the
      blastula stage, the only structural component of the nucleus seen in electron
      micrographs is a mass of chromatin fibrils. At the early gastrula stage, the
      primary nucleoli originate as small dense fibrous bodies within the chromatin
      material. These dense fibrous nucleoli enlarge during successive developmental
      stages by the acquisition of granular components 150 A in diameter, which form a
      layer around them. Simultaneously larger granules (300 to 500 A) appear in the
      chromatin, and they fill the interchromatin spaces by the tail bud stage.
      Autoradiographic examination has demonstrated that nuclear RNA synthesis takes
      place in both the nucleolus and the chromatin, with the former consistently
      showing more label per unit area than the latter. When changes in the
      distribution pattern of radioactivity were studied 3 to 24 hours after immersion
      in isotope at each developmental stage, the following results were obtained.
      Labeled RNA is first localized in the fibrous region of the nucleolus and in the
      peripheral region of chromatin material. After longer culture in non-radioactive
      medium, labeled materials also appear in the granular region of the nucleolus and
      in the interchromatin areas. Further incubation gives labeling in cytoplasm.

PMID- 19866690
TI  - A MICROTUBULAR COMPLEX IN THE EPIDERMAL NUCLEUS OF AN INSECT, CARAUSIUS MOROSUS.

PMID- 19866691
TI  - THE COMPOUND EYE OF A CRUSTACEAN, LEPTODORA KINDTII.

PMID- 19866692
TI  - CRYSTALLOID STRUCTURE IN GRANULES OF GUINEA PIG BASOPHILS AND HUMAN MAST CELLS.

PMID- 19866693
TI  - ULTRASTRUCTURE OF THE HEPATIC SINUSOID OF THE GOAT CAPRA HIRCUS.

PMID- 19866694
TI  - METHOD FOR COMBINED ULTRASTRUCTURAL AND BIOCHEMICAL ANALYSIS OF NEURAL TISSUE.
AB  - No significant change was found in the electrolytes and lipids of the brain
      analyzed after glutaraldehyde fixation by perfusion of laboratory animals; such
      fixation also satisfactorily preserves neural tissues for electron microscopy.
      The brains of normal and tumor-bearing C3H mice, Wistar rats, and New Zealand
      rabbits were studied. Little difference was found in the dry weight and the
      content of sodium, potassium, total lipid and lipid fractions, and in the sulfate
      space (S(35)O(4)) between specimens from unperfused and perfused animals, whether
      normal or tumor-bearing. The results suggest the possibility of using selected
      regions of the nervous system, dissected after fixation, for chemical study and
      at the same time characterizing similar regions morphologically with the electron
      microscope.

PMID- 19866695
TI  - CYTOPLASMIC MICROTUBULE AND WALL MICROFIBRIL ORIENTATION IN ROOT HAIRS OF RADISH.
AB  - The fine structure of young root hairs of radish was studied, with special
      attention to cytoplasm-wall relationships. Hairs up to 130 micro in length were
      examined after fixation of root tips in glutaraldehyde followed by osmium
      tetroxide. Microtubules occur axially aligned in the cytoplasm just beneath the
      plasmalemma, and extend from the base of the hair to within 2 to 3 micro of the
      tip. Poststaining with uranyl acetate and lead citrate clearly reveals in thin
      sections the presence of the two layers of cellulose microfibrils known from
      studies on shadowed wall preparations: an outer layer of randomly arranged
      microfibrils arising at the tip, and a layer of axially oriented microfibrils
      deposited on the inside of this layer along the sides. The youngest microfibrils
      of the inner, oriented layer first appear at a distance of about 25 micro from
      the tip. Although the microfibrils of the inner layer and the adjacent
      microtubules are similarly oriented, the oriented microtubules also extend
      through the 20- to 25-micro zone near the tip where the wall structure consists
      of random microfibrils. This suggests that the role of microtubules in wall
      deposition or orientation may be indirect.

PMID- 19866696
TI  - On the plastids, mitochondria, and other cell constituents during oogenesis of a
      plant.
AB  - In the liverwort Sphaerocarpus donnellii Aust., the behavior of the cell
      constituents, especially of mitochondria and plastids, was studied by electron
      microscopy during the development of the egg and its preceding cells. A
      degeneration and elimination of mitochondria and plastids was not found in any of
      the developmental stages. In all growth phases of the archegonium, the plastids
      may deposit starch which becomes especially frequent in the maturing egg cell. No
      indications have been observed that new mitochondria or plastids generate from
      the nuclear evaginations, which often penetrate deeply into the cytoplasm of the
      maturing and fully developed eggs. A quantitative investigation based on general
      micrographs elucidates the numerical aspects of the cell constituents during
      oogenesis. With the increase of cell volume, the numbers of dictyosomes,
      mitochondria, plastids, and lipid bodies increase. From the stages of the mother
      cell of the axial row up to that of the mature egg, the cell volume enlarges
      about 8 times and the nucleus volume about 15 times. Simultaneously, the numbers
      of mitochondria and plastids increase up to 8 to 15 times. On the basis of these
      findings, mitochondria and plastids with three-dimensional narrow constrictions
      are interpreted as divisional stages.

PMID- 19866697
TI  - An analysis of DNA loss and synthesis in the rat adrenal medulla nuclei upon cold
      stimulation.
AB  - The peculiar changes previously observed in DNA content of rat adrenal medulla
      cell nuclei upon intermittent cold exposure (15 hr at +4 degrees C followed by 9
      hr at room temperature) have been further studied with the aid of Feulgen
      histophotometry and H(3)-thymidine radioautography. The amount of DNA decreases
      progressively with increasing length of cold exposure until 300 hr (-32%). Later
      a rapid change takes place, whereby DNA content per nucleus returns to values
      which are slightly, but consistently lower than normal. At termination of a
      period of cumulative exposure to cold, an analysis of a whole-day experimental
      cycle shows that the DNA decrease is due to loss of DNA during cold exposure and
      that DNA synthesis occurs upon return to room temperature. The balance between
      these two processes can be divided into three stages: (a) loss of DNA up to 300
      hr of cumulative cold exposure; (b) marked increase in DNA by 350 hr; (c)
      oscillation around zero or slightly negative at 400 hr and beyond. These
      variations are due to: (1) the extension of DNA synthesis into the period of cold
      exposure as clearly demonstrated by radioautography (stage b), and (2) a later
      still greater DNA loss (stage c) which partly offsets the increased synthesis. A
      complex pattern of adaptation of the adrenal medulla cells, as regards DNA
      content, to the repetitive cold stimulus is thus demonstrated.

PMID- 19866698
TI  - ACETYLCHOLINESTERASE IN FROG SYMPATHETIC AND DORSAL ROOT GANGLIA : A Study by
      Electron Microscope Cytochemistry and Microgasometric Analysis with the Magnetic
      Diver.
AB  - The localization and chemical determination of acetylcholin esterase in the frog
      sympathetic and dorsal root ganglia were studied by a combination of the methods
      of electron microscopy, histochemistry, and microgasometric analysis with the
      magnetic diver. The Koelle-Friedenwald copper thiocholine histochemical method
      was modified by eliminating the sulfide conversion and by treatment of the tissue
      with potassium permanganate. In fixed tissue, enzymatic activity was demonstrated
      on the inner surface of the endoplasmic reticulum, nuclear envelope, subsurface
      cisternae, and agranular reticulum of the perikaryon and axon. In briefly fixed
      tissue, end product appeared also at the axon-sheath and the sheath-sheath
      interface. Activity at the synaptic junction was most readily obtained in unfixed
      tissue. Isolated neurons recovered from the diver following chemical analysis
      were studied with the electron microscope. Cells having a high enzyme activity
      showed a badly ruptured or absent neural plasmalemma and sheath. In this case the
      measured activity was apparently due to the enzyme present in the endoplasmic
      reticulum. Neurons having low activity exhibited an intact plasmalemma and
      sheath. This may reflect the effectiveness of the neural plasmalemma and sheath
      as a penetration barrier. The effects of fixation on enzyme activity are
      discussed. Electron microscopic examination of cells following microgasometric
      analysis is shown to be essential for the interpretation of the biochemical data.

PMID- 19866699
TI  - On the relationship of liver glucose-6-phosphatase to the proliferation of
      endoplasmic reticulum in phenobarbital induction.
AB  - The differentiated effects of phenobarbital treatment on liver microsomal enzymes
      have been further studied. The relationship between the resulting decrease in the
      specific glucose-6-phosphatase activity and the enhancement of formation of
      endoplasmic reticulum membranes with high drug-hydroxylating activity has been
      investigated with biochemical and histochemical methods. Biochemically and
      histochemically demonstrable glucose-6-phosphatase activity was found to be
      present in all endoplasmic reticulum membranes, including the phenobarbital
      induced smooth-surfaced proliferates, even though there was an over-all decrease
      in activity. Actinomycin D did not inhibit the decrease in glucose-6-phosphatase
      activity. The findings are discussed with reference to the enzyme-membrane
      relationship in phenobarbital induction.

PMID- 19866700
TI  - The relationship of the "sphere chromatophile" to the fate of displaced histones
      following histone transition in rat spermiogenesis.
AB  - Cytochemical, radioautographic, and microspectrophotometric studies bearing on
      the relationship of histone transition to the origin and development of the
      protein and RNA components of the "sphere chromatophile" in the developing
      spermatogenic cells of the albino rat are presented. These studies show that the
      sphere chromatophile has many features in common with somatic nuclei: it contains
      histonelike basic proteins rich in lysine, with lesser amounts of arginine. No
      evidence is found for the presence of a protamine in this granule. The sphere
      chromatophile is rich in RNA, but contains no DNA. The failure of a positive
      reaction with basic protein stains, unless the RNA is first removed, indicates
      either a chemical bonding or a very close association between the RNA and basic
      protein. The basic protein and RNA components of the sphere chromatophile appear
      to have different origins in the cell. A sequence of stages in the development of
      the lysine-rich basic protein component of this structure commences with the
      appearance of tiny grains in those spermatid nuclei which are beginning to
      replace lysine-rich histones with arginine-rich histones. Subsequently, similar
      staining cytoplasmic grains appear, which coalesce to form the sphere
      chromatophile in the cytoplasm. Labeling studies show that the basic protein
      component is synthesized at about the time of the last premeiotic DNA (and
      histone) synthesis. The results of the microspectrophotometric measurements
      support the idea that the basic protein lost from the spermatid nucleus is the
      source of the basic protein in the sphere chromatophile.

PMID- 19866701
TI  - THE RELATIONSHIP BETWEEN RNA SYNTHESIS AND HEMOGLOBIN SYNTHESIS IN AMPHIBIAN
      ERYTHROPOIESIS : Cytochemical Evidence.
AB  - A cytochemical study of the relationship between RNA synthesis and hemoglobin
      synthesis has been performed on splenectomized newts, Triturus viridescens.
      Employing radioautography, labeled cytidine was incorporated into the RNA of the
      early developmental stages but was not incorporated in the later stages. Labeled
      leucine was incorporated into the cellular protein of all stages except mature
      erythrocytes but was incorporated at a higher level in the later stages.
      Microphotometric measurements of azure B binding to cytoplasmic RNA revealed a
      sharp initial increase between the stem cell and proerythroblast followed by a
      rapid decrease between the basophilic and polychromatophilic stages. The loss of
      cytoplasmic RNA became more gradual in the late stages and, in the mature
      erythrocyte, little or no cytoplasmic RNA could be detected. Measurements of
      cytoplasmic total protein, using fast green staining at pH 2.0, and of heme
      showed that both curves increased similarly with development, indicating net
      hemoglobin synthesis. The results are compatible with the hypothesis that, as the
      stem cell differentiates along erythrocytic lines, a stable "messenger" RNA
      specifying the production of a given type or types of hemoglobin is formed. This
      complex probably becomes associated with ribosomal RNA and is retained throughout
      the process of RBC differentiation.

PMID- 19866702
TI  - THYMIDINE TRIPHOSPHATE SYNTHESIS IN TETRAHYMENA: I. Studies on Thymidine Kinase.
AB  - The amount of thymidine-H(3) converted to thymidine-H(3) monophosphate in 30 min
      formed the basis for assays of thymidine kinase in cell extracts from Tetrahymena
      pyriformis. The optimal concentration of adenosine triphosphate is lower than
      that required by other cell types. Thymidine triphosphate does not exercise any
      feedback control of the enzyme. Other deoxyprimidine nucleotides were tested, but
      these also failed to exhibit any feedback inhibition. At suboptimal adenosine
      triphosphate levels, thymidine triphosphate and other deoxypyrimidine nucleotides
      stimulate the reaction, suggesting that these nucleotides may act either directly
      or indirectly as phosphate donors in the crude enzyme preparations. This
      possibility was affirmed when thymidine triphosphate and deoxycytidine
      triphosphate were shown to be capable of limited phosphorylation of thymidine.
      Comparison of enzymatic activities in logarithmically growing culture and
      stationary phase culture, in which nuclear DNA synthesis has virtually ceased,
      reveals no change in enzymatic activity. The results suggest that thymidine
      kinase is a constitutive enzyme in Tetrahymena.

PMID- 19866703
TI  - HEPATIC INTRACELLULAR OSMIOPHILIC DROPLETS : Effect of Lipid Solvents during
      Tissue Preparation.
AB  - Lipid solvent extraction of aldehyde-fixed hepatic tissue of rats caused
      disappearance of all intravascular and hepatocellular osmiophilic droplets
      normally present, thus indicating their lipid content. Intramitochondrial dense
      granules and osmiophilic droplets in lysosomes also disappeared after this
      treatment. Lipid solvents extracted 43.8 to 92.6% of the radioactivity from
      aldehyde-fixed rat liver with C(14)-labeled lipids. Only 0.7 to 5.8% of the
      radioactivity was extracted when the hepatic proteins were labeled. When tissue
      was fixed with OsO(4), the lipid solvents extracted only 0.7 to 7.2% of the
      radioactivity from lipid-labeled liver and only 0 to 0.7% when proteins were
      labeled. Thin layer chromatography of the lipid solvents used in extraction of
      formaldehyde-fixed tissue revealed that triglyceride, phospholipid, and
      cholesterol and other lipid classes had been removed. However, acetone extracted
      less phospholipids than did ethanol or methanol-chloroform. During fat absorption
      the number and size of osmiophilic droplets increased in the nongranular
      endoplasmic reticulum. In animals fasted up to 5 days, 250-A osmiophilic
      particles were still present in the Golgi vesicles, other cytoplasmic vesicles,
      and in the space of Disse. These were considered possibly to represent
      lipoprotein being synthesized in the liver cell and secreted into the blood.

PMID- 19866704
TI  - Lysosome function in the regulation of the secretory process in cells of the
      anterior pituitary gland.
AB  - The nature and content of lytic bodies and the localization of acid phosphatase
      (AcPase) activity were investigated in mammotrophic hormone-producing cells (MT)
      from rat anterior pituitary glands. MT were examined from lactating rats in which
      secretion of MTH(1) was high and from postlactating rats in which MTH secretion
      was suppressed by removing the suckling young. MT from lactating animals
      contained abundant stacks of rough-surfaced ER, a large Golgi complex with many
      forming secretory granules, and a few lytic bodies, primarily multivesicular
      bodies and dense bodies. MT from postlactating animals, sacrificed at selected
      intervals up to 96 hr after separation from their suckling young, showed (a)
      progressive involution of the protein synthetic apparatus with sequestration of
      ER and ribosomes in autophagic vacuoles, and (b) incorporation of secretory
      granules into multivesicular and dense bodies. The content of mature granules
      typically was incorporated into dense bodies whereas that of immature granules
      found its way preferentially into multivesicular bodies. The secretory granules
      and cytoplasmic constituents segregated within lytic bodies were progressively
      degraded over a period of 24 to 72 hr to yield a common residual body, the
      vacuolated dense body. In MT from lactating animals, AcPase reaction product was
      found in lytic bodies, and in several other sites not usually considered to be
      lysosomal in nature, i.e., inner Golgi cisterna and associated vesicles, and
      around most of the immature, and some of the mature secretory granules. In MT
      from postlactating animals, AcPase was concentrated in lytic bodies; reaction
      product and incorporated secretory granules were frequently recognizable within
      the same multivesicular or dense body which could therefore be identified as
      "autolysosomes" connected with the digestion of endogenous materials. Several
      possible explanations for the occurrence of AcPase in nonlysosomal sites are
      discussed. From the findings it is concluded that, in secretory cells, lysosomes
      function in the regulation of the secretory process by providing a mechanism
      which takes care of overproduction of secretory products.

PMID- 19866705
TI  - The structure of eosinophil leukocyte granules in rodents and in man.
AB  - The structure of the specific granules of eosinophil leukocytes has been studied
      by electron microscopy in sections of tissues, buffy coats, and sediments of
      peritoneal washings of rats, mice, guinea pigs, and men. The core of eosinophil
      granules is a crystal which has a cubic lattice with a repeat of approximately 30
      A in rodents and approximately 40 A in man. The chemical composition of the core
      is discussed in connection with recent cell fractionation studies, and the
      hypothesis that the core is a crystal of peroxidase is considered.

PMID- 19866706
TI  - A morphological and functional study on a cluster of identifiable neurosecretory
      cells in the abdominal ganglion of aplysia californica.

PMID- 19866707
TI  - The location of sodium in the transverse tubules of skeletal muscle.

PMID- 19866708
TI  - The relationship between myofilament packing density and sarcomere length in frog
      striated muscle.
AB  - In cross-sections of single fibers from the frog semitendinosus muscle the number
      of thick myofilaments per unit area (packing density) is a direct function of the
      sarcomere length. Our data, derived from electron microscopic studies, fit well
      with other data derived from in vivo, low-angle X-ray diffraction studies of
      whole semitendinosus muscles. The data are consistent with the assumption that
      the sarcomere of a fibril maintains a constant volume during changes in sarcomere
      length. The myofilament lattice, therefore, expands as the sarcomere shortens.
      Since the distance between adjacent myofilaments is an inverse square root
      function of sarcomere length, the interaction of the thick and the thin
      myofilaments during sarcomere shortening may occur over distances which increase
      70 A or more. The "expanding-sarcomere, sliding-filament" model of sarcomere
      shortening is discussed in terms of the current concepts of muscle architecture
      and contraction.

PMID- 19866709
TI  - Light and electron microscopic radioautography of hepatic cell nucleoli in mice
      treated with actinomycin d.
AB  - Nucleolar partition induced by actinomycin D was used to demonstrate some aspects
      of nucleolar RNA synthesis and release in mouse hepatic cells, with light and
      electron microscopic radioautography. The effect of the drug on RNA synthesis and
      nucleolar morphology was studied when actinomycin D treatment preceded labeling
      with tritiated orotic acid. Nucleolar partition, consisting of a segegration into
      granular and fibrillar parts was visible if a dosage of 25 microg of actinomycin
      D was used, but nucleolar RNA was still synthesized. After a dosage of 400 microg
      of actinomycin D, nucleolar RNA synthesis was completely stopped If labeling with
      tritiated orotic acid preceded treatment with 400 microg of actinomycin D,
      labeled nucleolar RNA was present 15 min after actinomycin D treatment while high
      resolution radioautography showed an association of silver grains with the
      granular component. At 30 min after actinomicyn D treatment all labeling was
      lost. Since labeling was associated with the granular component the progressive
      loss of label as a result of actinomycin D treatment indicated a release of
      nucleolar granules. The correlation between this release and the loss of 28S RNA
      from actinomycin D treated nucleoli as described in the literature is discussed.

PMID- 19866710
TI  - Differentiation of the sarcoplasmic reticulum and T system in developing chick
      skeletal muscle in vitro.
AB  - The electron microscope was used to investigate the first 10 days of
      differentiation of the SR and the T system in skeletal muscle cultured from the
      breast muscle of 11-day chick embryos. The T-system tubules could be clearly
      distinguished from the SR in developing muscle cells fixed with glutaraldehyde
      and osmium tetroxide. Ferritin diffusion confirmed this finding: the ferritin
      particles were found only in the tubules identified as T system. The
      proliferation of both membranous systems seemed to start almost simultaneously at
      the earliest myotube stage. Observations suggested that the new SR membranes
      developed from the rough-surfaced ER as tubular projections. The SR tubules
      connected with one another to form a network around the myofibril. The T-system
      tubules were formed by invagination of the sarcolemma. The early extension of the
      T system by branching and budding was seen only in subsarcolemmal regions.
      Subsequently the T-system tubules could be seen deep within the muscle cells.
      Immediately after invaginating, the T-system tubule formed, along its course,
      specialized connections with the SR or ER: triadic structures showing various
      degrees of differentiation. The simultaneous occurrence of myofibril formation
      and membrane proliferation is considered to be important in understanding the
      coordinated events resulting in the differentiated myotube.

PMID- 19866711
TI  - Localization of Acid phosphatase in lipofuscin granules and possible autophagic
      vacuoles in interstitial cells of the Guinea pig testis.
AB  - The intracellular localization of acid phosphatase in guinea pig testicular
      interstitial cells was investigated by incubating nonfrozen thick sections of
      glutaraldehyde-perfused testis in a modified Gomori medium and preparing the
      tissue for electron microscopy. Lipofuscin pigment granules in these cells
      contain dense pigment, granular matrix, and often a lipid droplet. Reaction
      product is seen in the matrix of the pigment granules, and they may therefore be
      called residual bodies. At least some of the dense pigment appears to be derived
      from myelin figures and membrane whorls, since suitable intermediates can be
      seen. Lipid droplets found free in the cytoplasm are another possible source of
      pigment. In both cases the chemical mechanism is presumed to be autoxidation of
      unsaturated lipid. Acid phosphatase is present in the inner cisterna of Golgi
      elements. Enzyme activity also appears in possible autophagic vacuoles bounded by
      double membranes; the reaction product lies between the membranes. Consideration
      of the enzyme as a tracer suggests that the autophagic vacuoles are derived from
      the Golgi complex. Possible stages in the formation of these vacuoles by the
      inner Golgi cisternae are observed.

PMID- 19866712
TI  - The mechanism of mitochondrial extrusion from phenylhydrazine-induced
      reticulocytes in the circulating blood.
AB  - The mechanism of mitochondrial extrusion from reticulocytes was studied in whole
      blood from dogs made anemic by treatment with phenylhydrazine hydrochloride. The
      initial stage of preparation for mitochondrial extrusion was attraction of
      vesicles to mitochondria. There was subsequent encirclement of the organelle and
      other bodies, such as ferritin, by coalesced vesicles forming double membrane
      limited vacuoles. Large vacuoles were formed from the union of single vacuoles,
      and they were usually situated near the periphery of the cell. Fusion of the
      outer membrane of vacuoles with the plasmalemma of the reticulocyte provided a
      route for exposure and release of mitochondria and other material to an
      extracellular location. An extracellular mitochondrion, therefore, was confined
      by its original double membrane, and a third membrane was derived from the
      internal boundary of vacuoles.

PMID- 19866713
TI  - The effect of mitotic inhibitors on myogenesis in vitro.
AB  - The effect of colchicine and other antimitotic drugs was studied in cultures of
      11-day chick embryo breast muscle. Exposure of such cultures to 10(-6)M
      colchicine results in fragmentation of the elongate myotubes into rounded,
      cytoplasmic sacs (myosacs) containing various numbers of nuclei. Comparison of
      the dose-response relation between myotube fragmentation and metaphase arrest
      suggests that the underlying mechanism may be similar in both cases. Low
      temperature does not duplicate the effects of colchicine. Glycerinated myotubes
      are not affected by the mitotic inhibitors. The effect of colchicine on myotubes
      is reversible. Myosacs elongate within several days after removal from
      colchicine. However, the regenerated myotubes fail to incorporate additional
      mononucleated cells. Colchicine does not interfere with the process of fusion
      itself, but the metaphase block prevents cells from entering that phase of the
      cell cycle during which fusion can occur. Cells arrested in mitosis by colchicine
      do not recover when incubated in normal medium. Colcemid-induced arrest is
      reversible and does not prevent subsequent fusion of the cells.

PMID- 19866714
TI  - Ultrastructural studies on the lymphatic anchoring filaments.
AB  - The fine structure of the lymphatic capillary and the surrounding tissue areas
      was investigated. Instead of a continuous basal lamina (basement membrane)
      surrounding the capillary wall, these observations revealed the occurrence of
      numerous fine filaments that insert on the outer leaflet of the trilaminar unit
      membrane of the lymphatic endothelium. These filaments appear as individual
      units, or they are aggregated into bundles that are disposed parallel to the long
      axis of the lymphatic capillary wall and extend for long distances into the
      adjoining connective tissue area among the collagen fibers and connective tissue
      cells. The filaments measure about 100 A in width and have a hollow profile. They
      exhibit an irregular beaded pattern along their long axis and are densely stained
      with uranyl and lead. These filaments are similar to the microfibrils of the
      extracellular space and the filaments observed in the peripheral mantle of the
      elastic fibers. Infrequently, connections between these various elements are
      observed, suggesting that the lymphatic anchoring filaments may also contribute
      to the filamentous units of the extracellular space. It is suggested that these
      lymphatic anchoring filaments connect the small lymphatics to the surrounding
      tissues and represent the binding mechansim that is responsible for maintaining
      the firm attachment of the lymphatic capillary wall to the adjoining collagen
      fibers and cells of the connective tissue area.

PMID- 19866715
TI  - The effects of osmotic lysis on the oxidative phosphorylation and
      compartmentation of rat liver mitochondria.
AB  - Rat liver mitochondria isolated in 0.25 M sucrose were osmotically lysed with
      distilled water. The effect of osmotic lysis on mitochondrial compartmentation
      was monitored by following the changes in the specific Mg(++)-ATPase and the
      stimulation of this activity by DNP. Each resuspension in distilled water caused
      a progressive increase in the specific Mg(++)-ATPase and a decrease in DNP
      stimulation. Lysed mitochondria yielded P:O ratios of slightly less than 1.0 when
      each of the "site-specific" substrates, NADH, D-beta-hydroxybutyrate, succinate,
      and ascorbate, were oxidized. These data indicate that only site 3
      phosphorylation remained undiminished. The crude, lysed mitochondria were
      subfractionated by centrifugation on linear sucrose density gradients. Assays for
      protein, malate dehydrogenase, D-beta-hydroxybutyrate dehydrogenase, and
      succinate dehydrogenase indicated that the inner compartment could be clearly
      separated from the outer membrane vesicles. The results also suggested that the
      small vesicle fraction contained a small proportion of vesiculated inner
      membranes. Inner mitochondrial compartments, "contracted" by preincubation in the
      presence of ATP, sedimented to a markedly lower density on the gradients than did
      the unincubated preparations and about 50% of the ghosts showed a highly
      condensed morphology. In the contracted preparations, relatively low malate
      dehydrogenase and D-beta-hydroxybutyrate dehydrogenase activities were found in
      the fractions comprised of the inner compartments. The specific activity and
      distribution of succinate dehydrogenase were about the same as were found with
      the unincubated, lysed mitochondria.

PMID- 19866716
TI  - THE FINE STRUCTURE OF THE LATERAL VESTIBULAR NUCLEUS IN THE RAT : I. Neurons and
      Neuroglial Cells.
AB  - The lateral vestibular nucleus consists of multipolar isodendritic neurons of
      various sizes The distal segments of some dendrites display broad expansions
      packed with slender mitochondria and glycogen particles. These distinctive
      formations are interpreted as being growing tips of dendrites, and the suggestion
      is advanced that they are manifestations of architectonic plasticity in the
      mature central nervous system. Unlike large neurons elsewhere, the giant cells
      (Deiters) contain small Nissl bodies interconnected in a dense mesh-work. The
      Nissl substance is characterized by randomly arranged cisterns of the endoplasmic
      reticulum and by a high proportion of free ribosomes. Whether attached or free,
      ribosomes usually cluster in groups of four to six, and larger polysomal arrays
      are rare. Free ribosomal clusters also occur in the axon hillock and the initial
      segment. The neuronal perikarya contain distinctive inclusions consisting of a
      ball of neurofilaments enveloped by a complex honeycombed membrane. The failure
      of these fibrillary inclusions to stain with silver suggests that the putative
      argyrophilia of neurofilaments may reside in an inconstant matrix surrounding
      them. Giant cells of Deiters are in intimate contact with two kinds of cellular
      elements-astroglial processes and synaptic terminals. Oligodendroglial cells are
      only rarely satellites of giant cells; in contrast, they are frequently
      satellites of small and medium-sized cells.

PMID- 19866717
TI  - Effects of actinomycin d and puromycin on the acth-induced ultrastructural
      transformation of mitochondria of cortical cells of rat adrenals in tissue
      culture.
AB  - The ultrastructure of the mitochondria of the cultured cortical cells of rat
      adrenals was studied. In vivo it was found that the zona fasciculata mitochondria
      have vesicular internal structure. 600-A vesicles appear free in the matrix or as
      protrusions of the inner mitochondrial membrane. In tissue cultures of the fetal
      and newborn rat adrenal cortex it was seen that ACTH induces transformation of
      the tubulo-vesicular internal structure of the mitochondria to 600-A vesicles.
      Actinomycin D and puromycin inhibited this transformation if they were added with
      ACTH. When added alone, these inhibitors of protein synthesis induced no change
      in the ultrastructure of the mitochondria in cultured cortical cells of rat
      adrenals.

PMID- 19866718
TI  - The penetration of reovirus RNA and initiation of its genetic function in L
      strain fibroblasts.
AB  - Reovirus type 3 is phagocytized by L cells and rapidly sequestered inside
      lysosomes. Hydrolases within these organelles are capable of stripping the viral
      coat proteins, but they fail to degrade the double-stranded RNA genome. These
      observations support the view that sojourn of reovirus in lysosomes, when the
      lytic enzymes uncoat its genome, is an obligatory step in the sequence of
      infection. Although the mechanism for transferring the uncoated RNA out of
      lysosomes remains to be elucidated, evidence is presented suggesting that progeny
      genomes are bound to site(s) possessing the fine structure of viral inclusions or
      factories. It appears that both the synthesis of single- and double-stranded
      viral RNA and the morphogenesis of progeny virus particles occur in such
      factories.

PMID- 19866719
TI  - The use of millipore filters in ultrastructural studies of cell cultures and
      viruses.
AB  - A technique is described for embedding tissue culture cells that have been
      adsorbed or grown on Millipore filters. The acetone used during the embedding
      process rendered the filters transparent so that specific areas or cells could be
      chosen with the aid of the light microscope. Lymphoblastoid cells processed on
      the filters possessed well-defined plasma membranes and microvilli which were
      rarely present in cells from parallel cultures that were prepared by pelleting in
      the centrifuge. Fibroblast cells grown on filters retained their elongated
      appearance, in contrast to the rounded cells in pelleted preparations. Millipore
      filters were also used as a means of embedding virus pellets for sectioning.
      Preparations containing as few as 4 x 10(8) virus particles were suitable for
      study by the filter technique. Crude tissue-culture harvests of vaccinia virus
      and purified preparations of Rauscher murine leukemia and adeno-satellite viruses
      were successfully examined.

PMID- 19866720
TI  - OBLIQUELY STRIATED MUSCLE : IV. Sarcoplasmic Reticulum, Contractile Apparatus,
      and Endomysium of the Body Muscle of a Polychaete, Glycera, in Relation to Its
      Speed.
AB  - Body muscle cells of the bloodworm Glycera, a polychaete annelid, were studied by
      electron microscopy and compared with muscle cells of the more slowly acting
      nematode Ascaris, which have been described previously. Both muscles are
      obliquely striated. The predominant type of bloodworm fiber is characterized by a
      prominent transversely oriented sarcoplasmic reticulum with numerous dyads at the
      surface of each cell. Thick myofilaments are approximately 3 micro long and
      overlap along approximately 60% of their length in extended fibers and
      approximately 80% in shortened fibers. There is virtually no endomysium and very
      little intracellular skeleton, and the cells are attached by desmosomes to one
      another rather than to connective tissue. Dense bodies are absent from the fibers
      and in their place are Z lines, which are truly linear rather than planar.
      Scattered among the predominant fibers are others, less orderly in arrangement,
      in which the SR is much less prominent and in which the thick filaments are
      thicker and longer and overlap to an even smaller degree. It is suggested that
      physiological differences between bloodworm and Ascaris muscles derive from
      differences in the proportion of series to parallel linkages between the
      contractile elements, differences in the amount and disposition of the SR, and
      differences in the impedance to shear within the myofibrils.

PMID- 19866721
TI  - Ductal excretion of neutral red lysosomes in the mouse pancreas.

PMID- 19866722
TI  - Ultrastructure of chloroplasts isolated by nonaqueous extraction.

PMID- 19866723
TI  - Intercellular bridges and synchronization of germ cell differentiation during
      oogenesis in the rabbit.

PMID- 19866724
TI  - The thymidine pool in grasshopper neuroblasts during mitosis.

PMID- 19866725
TI  - Isolation of ribosomes from cysts of entamoeba invadens.
AB  - A reproducible method for the preparation of 75S ribosomes from cysts of
      Entamoeba invadens is presented. The method depends on the inactivation of the
      cyst's ribonuclease by high levels of Bentonite. The ribosomes are found to be
      extremely sensitive to ribonuclease, and to be stabilized by the addition of
      manganous and calcium ions to the magnesium customarily employed. Reasons are
      given for equating these ribosomes with the particles of which the crystalline
      chromatoid bodies are made.

PMID- 19866726
TI  - PROTEINS IN NUCLEOCYTOPLASMIC INTERACTIONS : II. Turnover and Changes in Nuclear
      Protein Distribution with Time and Growth.
AB  - In previous studies, we showed that essentially all the proteins of the Amoeba
      proteus nucleus could be classified either as Rapidly Migrating Proteins (RMP),
      which shuttle between nucleus and cytoplasm continuously at a relatively rapid
      rate during interphase, or as Slow Turnover Proteins (STP), which seem to move
      hardly at all during interphase. In this paper, we report on the kinetics and
      direction of the movement of both classes of protein, as well as on aspects of
      their localization, with and without growth. The effects of growth were observed
      with and without cell division. These nuclear proteins have been studied in
      several ways: by transplantation of labeled nuclei into unlabeled cells and
      noting the rate of distribution to cytoplasm and host cell nuclei; by repeated
      amputation of cytoplasm from labeled cells-with and without initially labeled
      cytoplasm-each amputation being followed by refeeding on unlabeled food; by
      noting the redistribution of the various protein classes following growth and
      cell division. The data show (a) labeled RMP equilibrate between a grafted
      labeled nucleus and an unlabeled host nucleus in ca. 3 hr, but are detectable in
      the latter less than 30 min after the operation; (b) STP label does, indeed,
      leave the nucleus and does so at a rate of ca. 25% of the nuclear total per cell
      generation (ca. 36-40 hr at 23 degrees C); (c) the cytoplasm appears to have a
      reserve of material that is converted to RMP; (d) when labeled cells are
      amputated just before they would have divided and are refed unlabeled food after
      each amputation, there is a loss of 20-25% of the nuclear protein label with each
      amputation; (e) under the latter circumstances, an essentially complete turnover
      of all nuclear protein can be demonstrated.

PMID- 19866727
TI  - LIPID SYNTHESIS, INTRACELLULAR TRANSPORT, AND STORAGE : III. Electron Microscopic
      Radioautographic Study of the Rat Heart Perfused with Tritiated Oleic Acid.
AB  - Rat hearts pulse-labeled by perfusion in vitro with 9,10-oleic acid-(3)H for 15
      or 30 sec were shown to take up the fatty acid extensively. In hearts
      postperfused with unlabeled medium for 15 sec or more, 90% of the radioactivity
      was recovered in esterified lipids. The radioautographic reaction was localized
      initially over elements of the sarcoplasmic reticulum and mitochondria. After
      longer periods of postperfusion (2-20 min), there was concentration of silver
      grains over lipid droplets. In mitochondria and sarcoplasmic reticulum isolated
      from hearts postperfused for 1 min or more, most of the esterified lipid was in
      the form of triglyceride. The ratio of the specific activity of isolated
      sarcoplasmic reticulum triglyceride to mitochondrial triglyceride changed from a
      value of 3.2 to 1.3 during 5 min of postperfusion. Under conditions of
      hypothermia, considerable uptake of free fatty acid occurred. The radioactivity
      recovered in the heart was mostly in the form of free fatty acid, and the
      radioautographic reaction was seen over sarcoplasmic reticulum and mitochondria,
      but not over lipid droplets or myofibrils. The results are interpreted to show
      that intracellular transport of free fatty acid, which occurs also when
      esterification is repressed, proceeds through intracellular channels, i.e. the
      sarcoplasmic reticulum. Esterification of fatty acid into triglycerides occurs
      mostly in the sarcoplasmic reticulum, especially in the region of the dyad, in
      the vicinity of which lipid is stored in the form of droplets.

PMID- 19866728
TI  - Some properties of the protein forming the outer fibers of cilia.
AB  - Cilia were isolated from Tetrahymena pyriformis by an ethanol-calcium procedure.
      Solutions of outer-fiber protein were obtained either by aqueous extraction of an
      acetone powder of whole cilia, or by dissolving the isolated outer-fibers in 0.6
      M KCl. In aqueous solution, the outer-fiber protein has a sedimentation
      coefficient of 6.0S and a molecular weight of 104,000 +/- 14,000. In 5 M
      guanidine hydrochloride solution the molecular weight falls to 55,000 +/- 5,000.
      After reduction and alkylation in 8 M urea, about 95% of the protein migrates as
      a single band on electrophoresis in polyacrylamide gel at pH 8.9; the migration
      velocity is identical with that of reduced and alkylated actin. Freshly prepared
      outer-fiber protein contains about 7.5 sulfhydryl groups per 55,000 g of protein.
      The amino acid composition of outer-fiber protein resembles that of actin, with
      such differences as occur being of the same order as those between actins from
      different species of animal.

PMID- 19866729
TI  - The effect of puromycin on intranuclear steps in ribosome biosynthesis.
AB  - Inhibition of protein synthesis by puromycin (100 gamma/ml) is known to inhibit
      the synthesis of ribosomes. However, ribosomal precursor RNA (45S) continues to
      be synthesized, methylated, and processed. Cell fractionation studies revealed
      that, although the initial processing (45S --> 32S + 16S) occurs in the presence
      of puromycin, the 16S moiety is immediately degraded. No species of ribosomal RNA
      can be found to have emerged from the nucleolus. The RNA formed in the presence
      of puromycin is normal as judged by its ability to enter new ribosomal particles
      after puromycin is removed. This sequence of events is not a result of inhibition
      of protein synthesis, for cycloheximide, another inhibitor of protein synthesis,
      either alone or in combination with puromycin allows the completion of new
      ribosomes.

PMID- 19866730
TI  - NUCLEAR BINDING OF EXOGENOUS HISTONES BY L CELLS AT LOW pH.

PMID- 19866731
TI  - The distribution of labeled norepinephrine within sympathetic nerve terminals
      studied with electron microscope radioautography.
AB  - The distribution of radioactivity in association with sympathetic nerve terminals
      and intraneuronal organelles 30 min after the administration of tritiated
      norepinephrine (NE-(3)H) was studied by electron microscope radioautography with
      recently developed quantitative methods of analysis reported in the accompanying
      paper (Salpeter et al., 1969). Nerves from the pineal body and the adrenal
      capsule were examined. It was found that nerve terminals containing vesicles were
      heavily labeled. (These terminals were not necessarily in contact with some
      innervated structure.) There was no selective labeling of either the
      intraneuronal mitochondria or the relatively small population of large (
      approximately 1000 A) dense core granules. Small vesicles ( approximately 500 A),
      some of which have a dense internal granule, could not be analysed separately
      because they are closely packed and occupy approximately 60% of the volume in
      terminals. Because of the extensive distribution of these small granular and
      agranular vesicles in the radioactive terminals, they remain the most likely site
      for norepinephrine binding. Yet although the vesicles were uniformly distributed
      within the nerve terminals, it appears that the radioactivity was not. There
      appeared to be a somewhat higher concentration of radioactivity at the periphery
      of the nerve terminals than in the center. The usefulness of the method of
      analysis used in this study for determining the location of bound H(3)NE pools in
      the nerve is discussed.

PMID- 19866732
TI  - STUDIES ON NUCLEAR STRUCTURE AND FUNCTION IN TETRAHYMENA PYRIFORMIS: I. RNA
      Synthesis in Macro- and Micronuclei.
AB  - Tetrahymena in the log phase of growth were pulse labeled with uridine-(3)H,
      fixed in acetic-alcohol, extracted with DNase, and embedded in Epon. 0.5-micro
      sections were cut, coated with Kodak NTB-2 emulsion, and developed after suitable
      exposures. Grains were counted above macronuclei, above 1000 micronuclei, and
      above 1000 micronucleus-sized "blanks" which were situated next to micronuclei in
      the visual field by means of a camera lucida. An analysis of grain counts showed
      that micronuclei were less than (1/2)(000) as active as macronuclei on the basis
      of grains per nucleus. Since micronuclei contained, on the average, about
      (1/2)(0) as much DNA as macronuclei, micronuclear DNA had less than 1% of the
      specific activity of macronuclear DNA in RNA synthesis. However, even this small
      amount of apparent incorporation was not significantly different from zero.
      Comparisons of the frequency distributions of labeled micronuclei with those of
      micronuclear "blanks" showed no evidence of a small population of labeled nuclei
      such as might be expected if micronuclei synthesized RNA for only a brief portion
      of the cell cycle. We conclude from these studies that there is no detectable RNA
      synthesis in Tetrahymena micronuclei during vegetative growth and reproduction.

PMID- 19866733
TI  - The effects of reserpine and hypoxia on the amine-storing granules of the hamster
      carotid body.
AB  - The carotid bodies from control, reserpine-treated, and hypoxia-treated hamsters
      were fixed with phosphate-buffered glutaraldehyde and osmium tetroxide, s
      Collidine-buffered osmium tetroxide, or phosphate-buffered glutaraldehyde
      followed by potassium dichromate incubation. Following glutaraldehyde-osmium
      tetroxide fixation no differences in density or population of the electron-opaque
      granules in the glomus cells of either control or experimental animals were
      observed. With s-Collidine-buffered osmium tetroxide and the glutaraldehyde
      dichromate technique a marked decrease in density without an appreciable
      reduction in number of granules was noted after reserpine treatment, while in
      hypoxia-treated hamsters the density and population of the granules were not
      different from those of the controls. The results indicate that reserpine
      depletes the amines without granule disappearance and that hypoxia does not
      affect the amine content of the granules. It is suggested that following
      glutaraldehyde-osmium tetroxide double fixation, persistence of the density of
      the granules in reserpine-treated animals is due primarily to the nonamine
      content, and that the amines in the glomus cells are probably not directly
      involved in the respiratory reflex.

PMID- 19866734
TI  - SURFACE STRUCTURE OF ISOLATED NEURONS : Detachment of Nerve Terminals during Axon
      Regeneration.
AB  - Freehand, isolated neuronal perikarya from the hypoglossal nucleus of the rabbit
      have been examined with light-and electron-microscopy (transmission and
      scanning). The surface of the cell bodies was largely covered with spherical
      particles which were 0.5-2 micro in diameter. Transmission electron microscopy
      proved that the spherical particles were synaptic nerve terminals. Crush of the
      hypoglossal nerve which leads to chromatolysis and swelling of the neuronal cell
      bodies results in a conspicuous reduction in the number of terminals attached to
      the surface of hypoglossal neurons. This effect was observed both for isolated
      neurons and in tissue sections. The effect is considered in relation to earlier
      reported variations in the adherence of neuropil to isolated neuronal perikarya.
      The functional importance of nerve ending detachment in connection with nerve
      injury is discussed.

PMID- 19866735
TI  - Protonation and chloroplast membrane structure.
AB  - Light changes the structure of chloroplasts. This effect was investigated by high
      resolution electron microscopy, photometric methods, and chemical modification.
      (a) A reversible contraction of chloroplast membrane occurs upon illumination,
      dark titration with H(+), or increasing osmolarity. These gross structural
      changes arise from a flattening of the thylakoids, with a corresponding decrease
      in the spacing between membranes. Microdensitometry showed that illumination or
      dark addition of H(+) resulted in a 13-23% decrease in membrane thickness.
      Osmotically contracted chloroplasts do not show this effect. (b) Rapid
      glutaraldehyde fixation during actual experiments revealed that transmission
      changes are closely correlated with the spacing changes and therefore reflect an
      osmotic mechanism, whereas the light scattering changes have kinetics most
      similar to changes in membrane thickness or conformation. (c) Kinetic analysis of
      light scattering and transmission changes with the changes in fluorescence of
      anilinonaphthalene sulfonic acid bound to membranes revealed that fluorescence
      preceded light scattering or transmission changes. (d) It is concluded that the
      temporal sequence of events following illumination probably are protonation,
      changes in the environment within the membrane, change in membrane thickness,
      change in internal osmolarity accompanying ion movements with consequent collapse
      and flattening of thylakoid, change in the gross morphology of the inner
      chloroplast membrane system, and change in the gross morphology of whole
      chloroplasts.

PMID- 19866736
TI  - The reaction of rat mast cells to polylysine.
AB  - The effects of a single intraperitoneal injection of polyamino acids (lysine,
      glutamic, aspartic) on mast cells of the rat are described. In vitro interaction
      of mast-cell components with these polyamino acids is also explored. Poly-DL
      lysine (but not the acidic amino acids) has both immediate (minutes-hours) and
      long-term (days-weeks) effects on mast cells. At the dosage selected, some cells
      evidence rapid fusion of granules and degranulation, but without concomitant
      swelling; most display intracellular changes only. Neither degranulation nor
      granule fusion appears to be lethal. Rather, these spur the cell to greater
      synthetic activity which involves first the Golgi apparatus and subsequently also
      the endoplasmic reticulum. Early involvement of macrophages and eosinophils is
      described. Sequential studies after polylysine injection support the following
      concepts: (a) mast-cell granules exist as "physiological sets," several being
      confined to a common membranous "sac;" (b) each set can respond independently to
      applied stimuli; (c) each set can connect directly to the extracellular milieu;
      (d) poly-DL-lysine binds directly to the granules and stabilizes them; it is not
      readily digested; (e) mast-cell granules are produced directly; they do not arise
      by intake of exogenous polysaccharides. It is hypothesized that mast-cell
      granules are topologically outside the cell while held intimately within
      extensive cytoplasmic folds and recesses. Mast cells may function by causing
      intercellular connective tissue fluids to percolate over their granules which may
      process this fluid in some as yet undefined way(s).

PMID- 19866737
TI  - Genesis of mitochondria in insect fat body.
AB  - Electron microscopy and stereological methods have been used to study the time
      course and mechanism of mitochondrial genesis in the adult fat body of Calpodes
      ethlius, (Lepidoptera, Hesperiidae). Most of the larval mitochondria are
      destroyed during a phase of autolysis shortly before pupation, so that pupal and
      early adult fat body cells have few mitochondria. The number of mitochondria per
      cell increases rapidly at the end of the 1st day after the adult emerges.
      Characteristic partitioned mitochondria appear during the period when the number
      is rapidly increasing. This evidence, coupled with the results of morphometric
      analyses of mitochondrial diameter, volume, and surface area, confirms the view
      that the genesis of adult mitochondria involves the growth and division of
      mitochondria surviving from the larva.

PMID- 19866738
TI  - Purification of intact microtubules from brain.
AB  - Hundred-fold purification of intact microtubules from homogenates of rat brain is
      reported. The success of purification depends on stabilizing the microtubule
      structure by the combined effects of hexylene glycol, acidic Ph, and low
      temperature. A practical, negative stain, electron microscopic assay is used to
      study purity and stability of microtubule fractions. The purified fractions show
      a major band which migrates like purified tubulin in the SDS gel electrophoresis
      system.

PMID- 19866739
TI  - Compartmentalization of the developing macronucleus following conjugation in
      stylonychia and euplotes.
AB  - The development of the macronucleus following conjugation in the hypotrichous
      ciliates Euplotes and Stylonychia has been examined with the electron microscope.
      Banded polytene chromosomes can be seen in thin sections of the macronuclear
      anlagen during the early periods of exconjugant development. As the chromosomes
      reach their maximum state of polyteny, sheets of fibrous material appear between
      the chromosomes and transect the chromosomes in the interband regions. Individual
      bands of the polytene chromosomes thus appear to be isolated in separate
      compartments. Subsequently, during the stage when the bulk of the polytenic DNA
      is degraded (1), these compartments swell, resulting in a nucleus packed with
      thousands of separate spherical chambers. Individual chromosomes are no longer
      discernible. The anlagen retain this compartmentalized condition for several
      hours, at the end of which time aggregates of dense material form within many of
      the compartments. The partitioning layers disperse shortly before replication
      bands appear within the elongating anlagen, initiating the second period of DNA
      synthesis characteristic of macronuclear development in these hypotrichs. The
      evidence presented here suggests that the "chromatin granules" seen in the mature
      vegetative macronucleus represent the material of single bands of the polytene
      chromosomes seen during the earlier stages of macronuclear development. The
      possibility is also discussed that the degradation of DNA in the polytene
      chromosomes may be genetically selective, which would result in a somatic
      macronucleus with a different genetic constitution than that of the micronucleus
      from which it was derived.

PMID- 19866740
TI  - Factors controlling the reassembly of the microvillous border of the small
      intestine of the salamander.
AB  - Hydrostatic pressure, when applied to segments of the small intestine of the
      salamander, causes a tremendous reduction in number of microvilli and a loss of
      the terminal web. The intestinal epithelium strips off from its deeper layers at
      the level of the basement membrane. When the pressure is released and this
      epithelial sheet is allowed to recover, the microvilli and its terminal web
      reappear. Stages in the reformation of microvilli are described. In the earliest
      stages, foci of dense material seem to associate with the cytoplasmic surface of
      the apical plasma membrane. From this material, filaments appear and their
      regrowth is correlated with the extension of the microvilli. We suggest that the
      dense material nucleates the assembly of the filaments which, in turn, appear
      instrumental in the redevelopment of microvilli. This concept is supported by the
      existing literature. Further, since neither the microvilli nor the terminal web
      reappear on any surface but the apical surface, even though the apical and basal
      surfaces are bathed with the same medium, we suggest that information in the
      membrane itself or directly associated with the membrane dictates the
      distribution of the dense material which leads to the formation of the microvilli
      and ultimately to the polarity of the cell.

PMID- 19866741
TI  - DEVELOPMENT OF THE NEUROMUSCULAR JUNCTION : II. Cytological and Cytochemical
      Studies on the Neuromuscular Junction of Dedifferentiating Muscle in the
      Regenerating Limb of the Newt Triturus.
AB  - Following amputation of the limb of the newt, Triturus viridescens, muscle fibers
      dedifferentiate giving rise to mesenchymal cells. The earliest changes detected
      in neuromuscular junctions of dedifferentiating muscle fibers are the appearance
      of a few vacuoles and decrease in density of the terminal axoplasm. Later,
      synaptic vesicles become tightly clustered in the axon termination, and their
      content appears denser than normal. Then, vesicles diminish in number until few
      are seen in the ending. While these changes are occurring, the area of contact of
      nerve with muscle becomes smaller. Junctional folds persist only where the nerve
      maintains contact with muscle, but these are shorter than normal and appear as
      slight ridges on the muscle surface. Subsequently, the nerve withdraws from the
      muscle cell and is completely invested by Schwann cell cytoplasm, and all traces
      of junctional folds are lost at the former region of contact. Cholinesterase
      activity was localized with the thiolacetic acid-lead nitrate method. Even before
      marked morphological changes occur in the junction, DFP- and physostigmine
      sensitive activity in the cleft between nerve and muscle is decreased in
      intensity. Activity continues to decrease as the area of nerve-muscle contact
      diminishes and junctional folds disappear. When the nerve has withdrawn from the
      muscle surface, only a few small deposits of lead are left in the intervening
      region. These results show that as muscle becomes less specialized during
      dedifferentiation, the neuromuscular junction also loses the cytological and
      cytochemical specializations associated with synaptic function.

PMID- 19866742
TI  - Histochemical staining and characterization of glycoproteins in Acid-secreting
      cells of frog stomach.
AB  - Glycoproteins were histochemically localized in oxyntic cells of the frog stomach
      by staining with periodic acid-silver methenamine. Reduction of silver was most
      intense on (a) the outer aspect of the apical plasmalemma, (b) within the tubular
      smooth membrane system characteristic of oxyntic cells, and (c) within cisternae
      and vesicles of the Golgi complex. Other membrane components such as those from
      the mitochondria, nucleus, junctional complex, lateral and basal cell membranes
      showed little or no stainability. Gastric mucosal homogenates were fractionated
      by centrifugation for further morphological and chemical analysis. The staining
      reaction of the microsomal fraction (40,000 g x 60 min) was similar to that of
      the tubular membranous components of intact oxyntic cells. Carbohydrate analyses
      showed that all cell fractions are extremely low in acidic sugars, uronic and
      sialic acids, while neutral sugars and hexosamines are relatively abundant. The
      microsomal fraction contains the largest proportion of carbohydrates, ca. 9% of
      the fat-free dry weight. Another distinguishing feature is that glucosamine is
      the only detectable hexosamine in the microsomal fraction. These histochemical
      and chemical data indicate that neutral glycoproteins are associated with
      membranous components which have been implicated in the process of HCl secretion
      by oxyntic cells. The staining pattern within the cells supports the hypothesis
      of interrelationships between the Golgi membranes, tubular smooth membranes, and
      apical surface membrane.

PMID- 19866743
TI  - REGULATION OF INITIATION OF DNA SYNTHESIS IN CHINESE HAMSTER CELLS : II.
      Induction of DNA Synthesis and Cell Division by Isoleucine and Glutamine in G(1)
      Arrested Cells in Suspension Culture.
AB  - Suspension cultures of Chinese hamster cells (line CHO), which had stopped
      dividing and were arrested in G(1) following growth to high cell concentrations
      in F-10 medium, could be induced to reinitiate DNA synthesis and to divide in
      synchrony upon addition of the appropriate amounts of isoleucine and glutamine.
      Both amino acids were required to initiate resumption of cell-cycle traverse.
      Deficiencies in other amino acids contained in F-10 medium did not result in
      accumulation of cells in G(1), indicating a specific action produced by limiting
      quantities of isoleucine and glutamine. In the presence of sufficient glutamine,
      approximately 2 x 10(-6)M isoleucine was required for all cells to initiate DNA
      synthesis in a population initially containing 1.5 x 10(5) cells/ml. Under
      similar conditions, about 4 x 10(-6)M isoleucine was required for all G(1)
      arrested cells to progress through cell division. In contrast, 1 x 10(-4)M
      glutamine was necessary for maximum initiation of DNA synthesis in G(1) cells,
      along with sufficient isoleucine. A technique for rapid production of G(1)
      arrested cells is described in which cells from an exponentially growing
      population placed in F-10 medium deficient in both isoleucine and glutamine or
      isoleucine alone accumulated in G(1) after 30 hr.

PMID- 19866744
TI  - Micronuclear ribonucleic Acid in tetrahymena pyriformis.
AB  - The presence of RNA in the micronucleus of Tetrahymena pyriformis was detected by
      electron microscope radioautography after incubation with tritiated precursors.
      The specificity of RNA labeling was shown by ribonuclease digestion. The period
      of appearance of labeled RNA in the micronucleus is approximately coincident with
      the DNA synthesis period for the micronucleus. Pulse-chase experiments showed
      that the micronuclear RNA disappears during the interphase period. The
      experiments do not distinguish whether the micronuclear RNA is synthesized in
      situ or acquired by migration from the macronucleus. In either case it is notable
      that the appearance of labeled RNA is detected in the micronucleus only during
      the micronuclear S phase.

PMID- 19866745
TI  - THE CELL JUNCTION IN A LAMELLIBRANCH GILL CILIATED EPITHELIUM : Localization of
      Pyroantimonate Precipitate.
AB  - The junctional complex in the gill epithelium of the freshwater mussel (Elliptio
      complanatus) consists of an intermediary junction followed by a 2-3 micro long
      septate junction. Homologous and heterologous cell pairs are connected by this
      junction. After fixation with 1% OsO(4) containing 1% potassium pyroantimonate,
      electron microscopy of the gill reveals deposits of electron-opaque precipitate,
      specifically and consistently localized along cellular membranes. In both
      junctional and nonjunctional membrane regions, the precipitate usefully outlines
      the convolutions without obliterating the 150 A intercellular space, which
      suggests the rarity or absence of either vertebrate-type gap or tight junctions
      along the entire cell border. The precipitate appears on the cytoplasmic side of
      the limiting unit membranes of frontal (F), laterofrontal (LF), intermediate (I),
      lateral (L), and postlateral (PL) cells. The membrane surfaces of certain
      vesicles of the smooth endoplasmic reticulum, of multivesicular bodies, and of
      mitochondrial cristae contain precipitate, as does the nucleolus. In other
      portions of the cell, precipitate is largely absent. The amount of over-all
      deposition is variable and depends on the treatment of the tissue prior to
      fixation. Deposition is usually enhanced by pretreatment with 40 mM NaCl as
      opposed to 40 mM KCl, which suggests that the precipitate is in part sodium
      pyroantimonate. Treatment with 0.2 mM ouabain does not enhance deposition.
      Regional differentiation of cell membranes with respect to their ability to
      precipitate pyroantimonate is found in at least three instances: (a) between the
      ciliary membranes and other portions of the cell membrane: the precipitate
      terminates abruptly at the ciliary base, (b) between the LF and I cell borders:
      the precipitate is asymmetric, favoring the LF side of the junction, and (c)
      between the septate junctional membrane and adjacent membrane: the precipitate
      occurs periodically throughout the septate junction region with the periodicity
      corresponding to the spacing of the septa. This suggests that different regions
      of the cell membrane may have differing ion permeability properties and, in
      particular, that the septa may be the regions of high ion permeability in the
      septate junction.

PMID- 19866746
TI  - STUDIES OF THE TRIAD : I. Structure of the Junction in Frog Twitch Fibers.
AB  - The structure of the junction between sarcoplasmic reticulum (SR) and transverse
      tubular (T) system at the triad has been studied in twitch fibers of the frog.
      The junction is formed by flattened surfaces of the SR lateral sacs and the T
      system tubule, which face each other at a distance of 120-140 A. At periodic
      intervals of about 300 A, the SR membrane forms small projections, whose tips are
      joined to the T system membrane by some amorphous material. The SR projections
      and the amorphous material are here called SR feet. The feet are disposed in two
      parallel rows, two such rows being present on either side of the T-system tubule.
      The junctional area between the feet is apparently empty. The feet cover no more
      than 30% of the T system surface area and 3% of the total SR area. The functional
      significance of this interpretation of the junctional structure is discussed.

PMID- 19866747
TI  - Physical chemical studies on the specific interaction of an acriflavine
      phosphotungstic Acid complex with double-stranded nucleic acids.
AB  - The detailed definition of the structure of DNA in chromosomes and in interphase
      chromatin is important for correlating the structure of the genetic material with
      various states of physiological activity. A general approach to developing
      specific reagents for a variety of such studies in solution and in tissues is to
      combine a chemically specific organic cation with the electron-opaque
      phosphotungstic acid (PTA) molecule. The reagent described in this paper was made
      from the interaction of acriflavine and phosphotungstic acid. The acriflavine-PTA
      complex (a) displays some unique absorption and fluorescence properties, (b)
      binds specifically to DNA and RNA by intercalation of the acriflavine moiety, and
      (c) is electron opaque. In addition, it binds to double-stranded synthetic
      polynucleotides, but not to a variety of proteins, nucleoproteins, or
      polysaccharides.

PMID- 19866748
TI  - Gap junctions occur in vertebrate renal proximal tubule cells.

PMID- 19866749
TI  - The mechanism of low-amplitude orthophosphate-induced swelling in isolated rat
      liver mitochondria.

PMID- 19866750
TI  - Vitamin b(12) and the macromolecular composition of euglena.

PMID- 19866751
TI  - Possible role of intranuclear membranes in nuclear-cytoplasmic exchange in spider
      crab oocytes.

PMID- 19866752
TI  - SYNCHRONIZATION OF A PROLIFERATIVE POPULATION IN A CULTURED PLANT TISSUE :
      Kinetic Evidence for a G(1)/S Population.

PMID- 19866753
TI  - Nerve-acinar cell relationships in the rat parotid gland.

PMID- 19866754
TI  - Antimotility effect of cytochalasin B observed in Mammalian clot retraction.

PMID- 19866755
TI  - Extracellular synaptic vesicles in the mouse heart.

PMID- 19866756
TI  - Free-flow electrophoretic separation and electrical surface properties of
      subcellular particles from Guinea pig brain.
AB  - Continuous free-flow electrophoretic separation has been used to obtain
      relatively pure preparations of synaptosomes and synaptic vesicles from crude
      fractions of guinea pig brain homogenates. Measurements of the contents of
      protein, neuraminic acid, and bound acetylcholine; the activities of succinic
      dehydrogenase, adenosine triphosphatase, choline acetylase, and 5'-nucleotidase;
      and the uptake of (14)C-labeled choline arid acetylcholine in the presence and
      absence of hemicholinium, all confirm the electron microscope evidence that the
      electrophoretic preparations are at least as pure as those obtained by
      ultracentrifugal methods. The electrophoretic mobility measurements have been
      used to calculate zeta potentials and surface charge densities for these
      particles.

PMID- 19866757
TI  - A pattern of epidermal cell migration during wound healing.
AB  - Epidermal repair during wound healing is under investigation at both the light
      and electron microscopic levels. Suction-induced subepidermal blisters have been
      employed to produce two complementary model wound healing systems. These two
      model systems are: (a) intact subepidermal blisters, and (b) opened subepidermal
      blisters (the blister roof was removed immediately after induction, leaving an
      open wound). From these studies a pattern of movement for epidermal cells in
      wound healing is proposed. This pattern of movement is the same for both model
      systems. Epidermal cells appear to move by rolling or sliding over one another.
      Fine fibers oriented in the cortical cytoplasm may play an important role in the
      movement of these epidermal cells. Also instrumental in mediating this movement
      are intercellular junctions (desmosomes) and a firm attachment to a substrate
      through hemidesmosomes. In the intact subepidermal blisters hemidesmosomal
      attachment is made to a continuous and homogeneous substrate, the retained basal
      lamina. In the opened subepidermal blisters contact of epidermal cells is made to
      a discontinuous substrate composed of sporadic areas of fibrin and underlying
      mesenchymal cells.

PMID- 19866758
TI  - DIFFERENTIATION OF ENDOPLASMIC RETICULUM IN HEPATOCYTES : I. Glucose-6
      Phosphatase Distribution In Situ.
AB  - The distribution of glucose-6-phosphatase activity in rat hepatocytes during a
      period of rapid endoplasmic reticulum differentiation (4 days before birth-1 day
      after birth) was studied by electron microscope cytochemistry. Techniques were
      devised to insure adequate morphological preservation, retain glucose-6
      phosphatase activity, and control some other possible artifacts. At all stages
      examined the lead phosphate deposited by the cytochemical reaction is localized
      to the endoplasmic reticulum and the nuclear envelope. At 4 days before birth,
      when the enzyme specific activity is only a few per cent of the adult level, the
      lead deposit is present in only a few hepatocytes. In these cells a light deposit
      is seen throughout the entire rough-surfaced endoplasmic reticulum. At birth,
      when the specific activity of glucose-6-phosphatase is approximately equal to
      that of the adult, nearly all cells show a positive reaction for the enzyme and,
      again, the deposit is evenly distributed throughout the entire endoplasmic
      reticulum. By 24 hr postparturition all of the rough endoplasmic reticulum, and
      in addition the newly formed smooth endoplasmic reticulum, contains heavy lead
      deposits; enzyme activity at this stage is 250% of the adult level. These
      findings indicate that glucose-6-phosphatase develops simultaneously within all
      of the rough endoplasmic reticulum membranes of a given cell, although
      asynchronously in the hepatocyte population as a whole. In addition, the enzyme
      appears throughout the entire smooth endoplasmic reticulum as the membranes form
      during the first 24 hr after birth. The results suggest a lack of differentiation
      within the endoplasmic reticulum with respect to the distribution of glucose-6
      phosphatase at the present level of resolution.

PMID- 19866759
TI  - DIFFERENTIATION OF ENDOPLASMIC RETICULUM IN HEPATOCYTES : II. Glucose-6
      Phosphatase in Rough Microsomes.
AB  - Electron microscope cytochemical localization of glucose-6-phosphatase in the
      developing hepatocytes of fetal and newborn rats indicates that the enzyme
      appears simultaneously in all the rough endoplasmic reticulum of a cell, although
      asynchronously within the hepatocyte population as a whole. To confirm that the
      pattern of cytochemical deposits reflects the actual distribution of enzyme
      sites, a method to subfractionate rough endoplasmic reticulum was developed. The
      procedure is based on the retention of the cytochemical reaction product
      (precipitated lead phosphate) within freshly prepared rough microsomes reacted in
      vitro with glucose-6-phosphate and lead ions. Lead phosphate increases the
      density of the microsomes which have glucose-6-phosphatase activity and thereby
      makes possible their separation from microsomes lacking the enzyme; separation is
      obtained by isopycnic centrifugation on a two-step density gradient. The
      procedure was applied to rough microsomes isolated from rats at several stages
      during hepatocyte differentiation and the results obtained agree with those given
      by cytochemical studies in situ. Before birth, when only some of the cells react
      positively for glucose-6-phosphatase, only a commensurate proportion of the rough
      microsome fraction can be rendered dense by the enzyme reaction. At the time of
      birth and in the adult, when all cells react positively, practically all
      microsomes acquire deposit and become dense after reaction. Thus, the results of
      the microsome subfractionation confirm the cytochemical findings; the enzyme is
      evenly distributed throughout all the endoplasmic reticulum of a cell and there
      is no regional differentiation within the rough endoplasmic reticulum with
      respect to glucose-6-phosphatase. These findings suggest that new components are
      inserted molecule-by-molecule into a pre-existing structural framework. The
      membranes are thus mosaics of old and new molecules and do not contain large
      regions of entirely "new" membrane in which all of the components are newly
      synthesized or newly assembled.

PMID- 19866760
TI  - The renewal of rod and cone outer segments in the rhesus monkey.
AB  - The renewal of retinal rod and cone outer segments has been studied by
      radioautography in rhesus monkeys examined 2 and 4 days after injection of
      leucine-(3)H. The cell outer segment consists of a stack of photosensitive,
      membranous discs. In both rods and cones some of the newly formed (radioactive)
      protein became distributed throughout the outer segment. Furthermore, in rods
      (but not in cones), there was a transverse band of concentrated radioactive
      protein slightly above the outer segment base 2 days after injection. This was
      due to the formation of new discs, into which labeled protein had been
      incorporated. At 4 days, these radioactive discs were located farther from the
      outer segment base. Repeated assembly of new discs had displaced them away from
      the basal assembly site and along the outer segment. Measurements of the
      displacement rate indicated that each retinal rod produces 80-90 discs per day,
      and that the entire complement of outer segment discs is replaced every 9-13
      days. To compensate for the continual formation of new discs, groups of old discs
      are intermittently shed from the apical end of the cell and phagocytized by the
      pigment epithelium. Each pigment epithelial cell engulfs and destroys about 2000
      4000 rod outer segment discs daily. The similarity between visual cells in the
      rhesus monkey and those in man suggests that the same renewal processes occur in
      the human retina.

PMID- 19866762
TI  - Sarcoplasmic reticulum and T tubules in differentiating rat skeletal muscle.
AB  - An electron microscope study has been made of the distribution of membrane
      couplings between the sarcoplasmic reticulum (SR) and either the plasmalemma or
      the T tubules in fetal and neonatal rat intercostal muscle. Within primitive
      muscle cells at 12 days of gestation, the SR forms both simple and specialized
      membrane junctions with the plasmalemma; caveolae are very few, and T tubules are
      not detected. Undifferentiated cells neighbor muscle cells. Occasionally these
      cells contain subsurface couplings between the endoplasmic reticulum and
      plasmalemmae. Possible relationships between these couplings and the peripheral
      couplings of muscle cells are discussed. By 15-18 days of gestation, caveolae and
      beaded T tubules, comparable to those of cultured muscle, develop; T tubules lie
      along-side myofibrils and are rarely transverse. SR couples both to T tubules and
      to plasmalemmae during this period. T tubules with lineal profiles appear after
      further development and their orientation transverse to A-I junctions becomes
      increasingly evident. Membrane couplings between SR and T tubules also increase
      in number, whereas the incidence of peripheral coupling declines rapidly Evidence
      suggests that peripheral couplings are swept into myotubes as caveolae
      proliferate and T tubules form. SR thus appears to initially couple with the
      plasmalemma and then to await T tubular growth. This contrasts with the
      developmental pattern described in cultured chick muscle in which peripheral
      couplings are not reported and T tubules with diads and triads occur at very
      primitive stages of muscle differentiation.

PMID- 19866761
TI  - The influence of intravascular fluid volume on the permeability of newborn and
      adult mouse lungs to ultrastructural protein tracers.
AB  - The permeability of the alveolar-capillary membrane of newborn and adult mice to
      horseradish peroxidase (HRP) and catalase was studied by means of ultrastructural
      cytochemistry, and the permeability to ferritin was studied by electron
      microscopy. The influence of varying volumes of intravenously injected fluid on
      the rate of leakage of the tracers from pulmonary capillaries was examined. The
      tracers were injected intravenously and the mice were sacrificed at timed
      intervals. Experiments on newborn mice with intranasally instilled HRP were also
      done. The tissues were fixed in formaldehyde-glutaraldehyde fixative. Chopped
      sections were incubated in Graham and Karnovsky's medium for peroxidase and in a
      modification of this medium for catalase. Tissues were postfixed in OsO(4) and
      processed for electron microscopy. In both newborn and adult mice, the ready
      passage of peroxidase through endothelial clefts was dependent on the injection
      of the tracer in large volumes of saline. When the tracer was injected in small
      volumes of saline, its passage through endothelial clefts was greatly reduced.
      Endothelial junctions of newborn mice were somewhat more permeable to HRP than
      those of adult mice. In all animals, alveolar epithelial junctions were
      impermeable to HRP. Catalase and ferritin did not pass through endothelial
      junctions. Intranasally instilled HRP in newborn mice was taken up by pinocytotic
      vesicles and tubules of flat alveolar cells.

PMID- 19866763
TI  - RADIOAUTOGRAPHY OF CHOLESTEROL IN LUNG : An Assessment of Different Tissue
      Processing Techniques.
AB  - 30 Swiss albino mice aged 8 days were injected intraperitoneally with 0.2 ml of a
      solution of 4% N,N-dimethyl-formamide in 5% dextrose in water containing
      cholesterol-1,2-(3)H ( approximately 1 mCi/ml). Lung tissue was embedded in an
      Epon mixture after either acetone and propylene oxide dehydration, partial
      ethanol and Epon 812 dehydration, or the precipitation of cholesterol by
      digitonin succeeded by partial dehydration. The distribution of cholesterol-1,2
      (3)H in lung parenchyma in 1micro Epon section radioautograms was compared with
      that in frozen section radioautograms and was found to be independent of the
      manner of tissue processing. Grain distribution in the tissue was essentially the
      same whether 16, 63, 93, or 100% radioactivity was retained in the lung. However,
      grain distribution in the alveolar spaces differed, presumably due to
      displacement of pulmonary surfactant, which contains cholesterol. Intracellular
      distribution of cholesterol, in electron microscope radioautograms, was the same
      with either 51% or 93% retention of radioactivity in the lung. Loss of
      radioactivity into the various processing solutions was monitored. The various
      processing techniques have different drawbacks.

PMID- 19866764
TI  - An electron microscopic study of the development of synapses in cultured fetal
      mouse cerebrum continuously exposed to xylocaine.
AB  - Explants of fetal mouse cerebral cortex, continuously exposed to the local
      anesthetic Xylocaine from the time of explantation to the time of fixation, were
      examined in the electron microscope to determine whether morphologically normal
      synapses and potentially functional interneuronal synaptic networks can form in
      the absence of electrical impulse activity. Morphological differentiation of
      complex synaptic networks proceeds normally, and the drug does not alter the fine
      structure of the formed synapses. These observations are consonant with the
      electrophysiological data which show that the potential for complex bioelectric
      activity can develop in the absence of its expression. The development and
      maturation of functional synaptic networks, then, is not contingent upon prior
      electrical impulse activity. These data support the concept that organized
      neuronal assemblies are formed in forward reference to their ultimate function.

PMID- 19866765
TI  - ERYTHROPOIESIS DURING AMPHIBIAN METAMORPHOSIS : I. Site of Maturation of
      Erythrocytes in Rana catesbeiana.
AB  - The site of maturation of the erythroid cells in premetamorphic, metamorphic, and
      adult stages of R. catesbeiana has been investigated by comparing the percentages
      of immature, hemoglobin-containing erythroid cells in circulating blood, liver,
      spleen, kidney, and bone marrow. In both premetamorphic and thyroxine-treated
      tadpoles, the liver was found to be the main site of maturation of the red cells.
      The corresponding site in the frog is the bone marrow.

PMID- 19866766
TI  - ERYTHROPOIESIS DURING AMPHIBIAN METAMORPHOSIS : II. Immunochemical Study of
      Larval and Adult Hemoglobins of Rana catesbeiana.
AB  - Rabbit antibodies were prepared against the major hemoglobin components of the
      larval and adult stages of R. catesbeiana. The properties of the antisera were
      studied by double immunodiffusion, precipitation, and complement fixation. The
      antisera to tadpole and frog hemoglobins did not cross-react with either
      hemoglobin or apohemoglobin. The anti-serum against frog hemoglobin was used for
      the detection of frog hemoglobin in tadpoles undergoing either natural or
      thyroxine-induced metamorphosis. It was shown that frog hemoglobin is detectable
      first in the liver, indicating that the liver is the site of erythrocyte
      maturation during metamorphosis.

PMID- 19866767
TI  - ERYTHROPOIESIS DURING AMPHIBIAN METAMORPHOSIS : III. Immunochemical Detection of
      Tadpole and Frog Hemoglobins (Rana catesbeiana) in Single Erythrocytes.
AB  - Rabbit antibodies specific for the major tadpole and frog hemoglobin components
      of R. catesbeiana were used for the detection of the two hemoglobins inside
      single cells. The antisera, after fractionation by ammonium sulfate precipitation
      and diethylaminoethyl (DEAE)-cellulose chromatography, were conjugated with
      fluorescein isothiocyanate for the antifrog hemoglobin serum and
      tetramethylrhodamine isothiocyanate for the antitadpole hemoglobin serum. The
      conjugated fractions, refractionated by stepwise elution from a DEAE-cellulose
      column, were used for the fluorescent staining of blood smears, liver tissue
      imprints, and smears of liver cell suspensions. Both simultaneous and sequential
      staining with the two fluorescent preparations indicated that larval and adult
      hemoglobins were not present within the same erythrocyte during metamorphosis. In
      other experiments, erythroid cells from animals in metamorphosis were spread on
      agar containing specific antiserum. Precipitates were formed around the cells
      which contain the particular hemoglobin. The percentages of cells containing
      either tadpole or frog hemoglobin were estimated within the experimental error of
      the method. The data showed that the two hemoglobins are in different cells. It
      is concluded that the hemoglobin change observed during the metamorphosis of R.
      catesbeiana is due to the appearance of a new population of erythroid cells
      containing exclusively frog hemoglobin.

PMID- 19866768
TI  - Studies on isolated aggregating oligoribonucleoproteins of the epidermis with
      histochemical and morphological characteristics of keratohyalin.
AB  - Histochemical and ultrastructural studies demonstrate that keratohyalin can be
      mobilized from fresh specimens of cattle hoof epidermis by 1.0 M potassium
      phosphate buffer (pH 7.0). Macroaggregates with histochemical characteristics
      identical to those of in situ keratohyalin granules (staining by Harris'
      hematoxylin, Congo red, diazotized sulfanilic acid, sodium alizarin sulfonate,
      toluidine blue, methyl green-pyronin, and acridine orange) and with similar
      morphological characteristics at the ultrastructural level are formed upon
      dialyzing the extracted keratohyalin against distilled water. Staining by basic
      dyes (toluidine blue, methyl green-pyronin, and acridine orange) is abolished by
      treating either in situ keratohyalin granules or isolated macroaggregates with
      ribonuclease. Electrophoresis of isolated macroaggregates on polyacrylamide gels
      in the presence of sodium decylsulfate results in the fractionation of a 13
      member oligomeric series of ribonucleoproteins and two non-homologous species of
      ribonucleoproteins. The oligomeric series can be purified by isolating "stacked"
      oligomers on low concentration (3%) polyacrylamide gels. Fractionated oligomers
      on polyacrylamide gels and aggregates formed from purified ribonucleoproteins
      demonstrate histochemical characteristics identical to those of in situ
      keratohyalin granules. Aggregates formed from denatured ribonucleoproteins are
      highly disordered and are markedly different from in situ keratohyalin granules
      or nondenatured isolated macroaggregates at the ultrastructural level, possibly
      due to irreversible denaturation of the oligomers by sodium decylsulfate.

PMID- 19866769
TI  - Isolation of nuclei from yeast.
AB  - A method for isolation of nuclei from Saccharomyces cervisiae in high yield is
      described. The DNA/protein ratio of the isolated nuclei is 10 times higher than
      that of whole cells. Examination of these nuclei in phase and electron
      microscopes has shown them to be round bodies having a double membrane,
      microtubules, and a dark crescent at one end. The optimum conditions for
      extraction and resolution of histones of these nuclei on acrylamide gels have
      been investigated. The nuclei have an active RNA polymerase (E.C. 2.7.7.6) and
      are able to synthesize RNA in vitro. They are also readily stainable with
      Giemsa's, Feulgen's, and acridine orange methods.

PMID- 19866770
TI  - Inhibition of emptying of skeletal muscle cell segments by adenine nucleotides
      and polyvalent cations.
AB  - A correlation had previously been established between actomyosin content of
      homogenized skeletal muscle cell segments as determined by extraction in strong
      salt solution and the ability of those segments to empty when extracted with
      buffered water. In this study, we examined the ability of certain compounds to
      inhibit the process of emptying. Adenosine triphosphate (ATP) and adenosine
      diphosphate (ADP), which dissociate actomyosin, inhibited the process of
      emptying, while adenosine monophosphate (AMP) which does not dissociate
      actomyosin, did not. We conclude that the formation of actomyosin is a necessary
      prerequisite for emptying and not just a secondary effect. Polyvalent cations
      were also found to inhibit emptying. The inhibition was reversible by washing
      with a solution of NaCl-histidine or with chelating agents,
      ethylenediaminetetraacetate (EDTA) and ethylene-glycol-bis(beta-amino-ethyl
      ether) tetraacetic acid (EGTA). A factor(s) solubilized from aged muscle
      functions as an inhibitory agent; the suggestion is made that this factor(s) may
      be a polyvalent cation.

PMID- 19866771
TI  - Transport of viral RNA in kb cells infected with adenovirus type 2.
AB  - Messenger RNA transport was studied in KB cells infected with the nuclear DNA
      virus adenovirus type 2. Addition of 0.04 microg/ml of actinomycin completes the
      inhibition of ribosome synthesis normally observed late after infection and
      apparently does not alter the pattern of viral RNA synthesis: Hybridization
      inhibition experiments indicate that similar viral RNA sequences are transcribed
      in cells treated or untreated with actinomycin. The polysomal RNA synthesized
      during a 2 hr labeling period in the presence of actinomycin is at least 60%
      viral specific. Viral messenger RNA transport can occur in the absence of
      ribosome synthesis. When uridine-(3)H is added to a late-infected culture
      pretreated with actinomycin, viral RNA appears in the cytoplasm at 10 min, but
      the polysomes do not receive viral RNA-(3)H until 30 min have elapsed. Only 25%
      of the cytoplasmic viral RNA is in polyribosomes even when infected cells have
      been labeled for 150 min. The nonpolysomal viral RNA in cytoplasmic extracts
      sediments as a broad distribution from 10S to 80S and does not include a peak
      cosedimenting with 45S ribosome subunits. The newly formed messenger RNA that is
      ribosome associated is not equally distributed among the ribosomes; by comparison
      to polyribosomes, 74S ribosomes are deficient at least fivefold in receipt of new
      messenger RNA molecules.

PMID- 19866772
TI  - LYSOZYME IN EPIPHYSEAL CARTILAGE : IV. Embryonic Chick Cartilage Lysozyme-Its
      Localization and Partial Characterization.
AB  - THE LOCALIZATION OF CHICK EMBRYONIC LYSOZYME WAS DETERMINED BY TWO TECHNIQUES: by
      studying the rate of release from the tissue during sequential enzymatic
      digestion and by immunocytochemistry. Both techniques indicate that, in this
      tissue, lysozyme is primarily extra-cellular. Cartilage lysozyme was isolated and
      partially characterized and found to be identical with egg white lysozyme in its
      immunologic and enzymatic behavior. In addition, a method for the isolation of
      large numbers of viable chondrocytes is described.

PMID- 19866773
TI  - ENZYME ACTIVITIES IN CHICK EMBRYONIC CARTILAGE : Their Subcellular Distribution
      in Isolated Chondrocytes.
AB  - Some characteristic enzymatic activities were determined in chick embryonic
      cartilage and compared with the analogous activities in bone and liver.
      Chondrocytes were isolated, broken by sonication, and subjected to subcellular
      fractionation to yield a nuclear pellet, the mitochondrial, lysosomal, and
      microsomal fractions, and the high speed supernatant solution. It was established
      that these fractions are characterized by enzymatic activities usually associated
      with similar fractions in other tissues, but with some quantitative differences.
      Lysozyme, a particulate-associated enzyme in other tissues, was not detected in
      any subcellular fraction even by the sensitive technique of microzone
      electrophoresis and is therefore considered to be primarily extracellular in
      cartilage.

PMID- 19866774
TI  - The distribution of spindle microtubules during mitosis in cultured human cells.
AB  - WI-38 and HeLa cells in mitosis have been selected from fixed monolayer cultures
      and serially sectioned for electron microscopy. Sections perpendicular to the
      spindle axis permit counting of the number of microtubules at each position on
      the spindle axis and hence the preparation of tubule distribution profiles.
      Errors intrinsic to this method are discussed. The changes in the tubule
      distributions from one mitotic stage to another provide evidence concerning the
      behavior of the spindle tubules during mitosis. The ratio of the number of
      tubules passing the chromosomes on the metaphase plate to the maximum number in
      each half spindle is about 1/2. This ratio changes little in early anaphase, and
      then decreases in late anaphase at about the same time that a zone of increased
      tubule number develops at the middle of the interzone. The region where the stem
      bodies form contains about 3/2 the number of tubules seen elsewhere in the
      interzone. This ratio is almost constant as the mid-body forms in telophase and
      then increases to 2/1 in early interphase before the final stages of cytokinesis
      occur.

PMID- 19866775
TI  - Relationships between nucleic Acid synthetic patterns and encystment in aging
      unagitated cultures of acanthamoeba castellanii.
AB  - Changes in the levels of DNA and RNA syntheses have been studied in unagitated
      cultures of Acanthamoeba castellanii during the phases of logarithmic
      multiplication (LM) and population growth deceleration (PGD). Pulse-labeling
      experiments show that the rate of DNA synthesis decreases at the same time that
      DNA per cell is known to drop by 50%. The drop in DNA content has been explained
      by demonstrating with hydroxyurea that the majority of LM amebas can replicate
      once when DNA synthesis is inhibited and, therefore, must be in G(2), whereas the
      PGD amebas cannot multiply in the presence of inhibitor and, therefore, must be
      in G(1). The inhibition of DNA synthesis in LM or PGD cells has been shown to
      induce encystment. The rate of RNA synthesis, as illustrated by pulse-labeling
      experiments, increases 25% in late LM-early PGD while RNA per cell increases 75%.
      The rate of synthesis then decreases 65%. The majority of accumulated RNA has
      been demonstrated to be ribosomal by disc electrophoresis. By using actinomycin D
      at different stages during the RNA build-up, the ability of the amebas to encyst
      has been shown to depend on the presence of this RNA. The observations on DNA and
      RNA are discussed with respect to the occurrence of cysts in the cultures during
      PGD.

PMID- 19866776
TI  - Morphological changes and the requirements for macromolecule synthesis during
      excystment of acanthamoeba castellanii.
AB  - Light and phase-contrast microscopic observations of excystment in Acanthamoeba
      castellanii have been used to classify cells in excysting populations as free
      trophozoites, or mature, activated, or preemergent cysts. These categories have
      been used to describe the kinetics of excystment. A pH of 7 and a temperature of
      30 degrees C have been found to be optimal for the activation of mature cysts.
      Both activation and emergence are inhibited by cycloheximide and actinomycin D,
      but neither process is much affected by hydroxyurea. Cell-free extracts of high
      molecular weight components of cyst cytoplasm can support protein synthesis in
      vitro, although less efficiently than similar extracts from trophozoites.
      Evidence indicates that some of the functional RNA in the cyst extracts is
      synthesized before excystment.

PMID- 19866777
TI  - Nexuses between areas of the surface membrane of the same arterial smooth muscle
      cell.

PMID- 19866778
TI  - Transport inhibitors released by 3t3 mouse cells and their relation to growth
      control.

PMID- 19866779
TI  - THE STIMULUS-SECRETION COUPLING OF GLUCOSE-INDUCED INSULIN RELEASE : IV. The
      Effect of Vincristine and Deuterium Oxide on the Microtubular System of the
      Pancreatic Beta Cell.

PMID- 19866780
TI  - SEPARATION OF MITOCHONDRIAL MEMBRANES OF NEUROSPORA CRASSA: I. Localization of L
      Kynurenine-3-Hydroxylase.

PMID- 19866781
TI  - Morphological studies of cells grown in the absence of mitochondrial-specific
      protein synthesis.

PMID- 19866782
TI  - Specific inhibition by ethidium bromide of mitochondrial DNA synthesis in
      physarum polycephalum.

PMID- 19866783
TI  - DNA-MEMBRANE COMPLEXES OF BACILLUS SUBTILIS: Contact of Mesosomal Vesicles and
      Nuclear Fibrils.

PMID- 19866784
TI  - Mitosis in adult newt ventricle.

PMID- 19866785
TI  - Uniqueness and location of the fracture plane in the plasma membrane of bacillus
      subtilis.

PMID- 19866787
TI  - Albert claude and the beginnings of biological electron microscopy.

PMID- 19866786
TI  - Tissue fraction-past and present.

PMID- 19866788
TI  - STUDIES ON THE BIOGENESIS OF SMOOTH ENDOPLASMIC RETICULUM MEMBRANES IN LIVERS OF
      PHENOBARBITAL-TREATED RATS : I. The Site of Activity of Acyltransferases Involved
      in Synthesis of the Membrane Phospholipid.
AB  - The localization of acyltransferases involved in acylation of alpha
      glycerophosphate, during phenobarbital induced proliferation of smooth
      endoplasmic reticulum (ser) membranes, has been investigated using cytochemical
      and cell fractionation techniques. In cytochemical studies of normal rat liver,
      reaction product marking acyltransferase activity was associated to the greatest
      extent with the rough endoplasmic reticulum (rer) membranes and to a lesser
      extent with ser membranes. In liver from phenobarbital-treated rats, reaction
      product was largely restricted to ser membranes. The specific activity of the
      acyltransferases of rough microsomes from normal rat liver was higher than that
      of the smooth microsomes. On injection of phenobarbital, this fell rapidly after
      three injections to a low level, at which it remained during subsequent
      treatment. The specific activity of the smooth microsomes, on injection of
      phenobarbital, rose to a peak 12 hr after the first injection, after which it
      fell to a level at an activity above that of smooth microsomes of normal liver. A
      mechanism is postulated for the biogenesis of smooth membranes in which the
      phospholipid is synthesized in situ and the protein is synthesized in the rer and
      moves to the site of newly synthesized phospholipid, where it is inserted to
      produce a whole membrane.

PMID- 19866789
TI  - A MITOCHONDRIAL INNER MEMBRANE PREPARATION THAT SEDIMENTS AT 100 g.

PMID- 19866790
TI  - THE VASCULAR CHANGES OF TUBERCULOUS MENINGITIS, ESPECIALLY THE TUBERCULOUS
      ENDARTERITIES.
AB  - 1. In tuberculosis meningitis there is a tuberculosis endarteritis characterized
      by the formation of intimal tubercles and a diffuse subendothelial, intimal
      proliferation due to implantation of tubercle bacili from the blood. From the
      endarteritis the infiltration may spread into the muscular coat and the
      adventitia, and the whole wall may undergo caseous and hyaline degeneration. 2.
      Tuberculous proliferation in the adventitia may invade the media and the intima,
      and the whole wall of the arterial segment may undergo degeneration. 3. The veins
      are constantly the seat of more or less extensive infiltration, which always
      results from adjacent extravascular or arterial foci. 4. The epithelioid cells of
      the subendothelial, tuberculous intimal See PDF for Structure proliferation are
      most likely derived from the subendothelial layer of connective tissue and not
      from the endothelial lining.

PMID- 19866791
TI  - THE PRODUCTION OF DIPHTHERIA TOXIN.
AB  - Toxin of sufficient strength to kill a 400-gramme guinea-pig in three days and a
      half in a dose of 0.cubic centimetre developed in suitable bouillon, contained in
      ordinary Erlenmeyer flasks, within a period of twenty-four hours. In such boullon
      the toxin reached its greatest strength in from four to seven days (0.005 cubic
      centimetre killing a 500-gramme guinea-pig in three days). This period of time
      covered that of the greatest growth of the bacilli, as shown both by the
      appearance of the culture and by the number of colonies developing an agar
      plates. The bodies of the diphtheria bacili did not at any time contain toxin in
      cosiderable amounts. The type of growth of the bacili and the rapidity and extent
      of the production of toxin depended more on the reaction of the bouillon than
      upon any other single factor. The best results were obtained in bouillon which,
      after being neutralized to litmus, had about seven cubic centimetres of normal
      soda solution added to each litre. An excessive amount of either acid or alkali
      prevented the development of toxin. Strong toxin was produced in bouillon
      containing peptone ranging from one to ten per cent. The strength of toxin
      averaged greater in the two and four-per-cent peptone solutions than in the one
      percent. When the stage of acid reaction was brief and the degree of acidity
      probably slight, strong toxin developed while the culture bouillon was still
      acid; but when the stage of acid reaction was prolonged, little if any toxin was
      produced until just before the fluid became alkaline. Glucose is deleterious to
      the growth of the diphtheria bacillus and to the production of toxin when it is
      present in sufficient amounts to cause by its disintegration too great a degree
      of acidity in the fluid culture. When the acid resulting from decomposition of
      glucose is neutralized by the addition of alkali the diphtheria bacilus again
      grows abundantly. Glucose is not present, at least as a rule, in sufficient
      amounts in the meat as obtained from the New York butchers to prevent the rapid
      production of strong toxin if the bouillon is made sufficiently alkaline. In our
      experiments, when other conditions were similar, the strength of the toxin was in
      proportion to the virulence and vigour of growth of the bacillus employed.

PMID- 19866792
TI  - THE MUCIN OF WHITE FIBROUS CONNECTIVE TISSUE.

PMID- 19866793
TI  - ON THE ACTION OF PIPERIDINE AND SOME OF ITS COMPOUNDS.

PMID- 19866794
TI  - FURTHER RESEARCHES ON THE CLOSURE OF THE CORONARY ARTERIES.

PMID- 19866795
TI  - OBSERVATIONS CONCERNING THE BACILLUS AEROGENES CAPSULATUS.

PMID- 19866796
TI  - THE EFFECT OF ODOURS, IRRITANT VAPOURS, AND MENTAL WORK UPON THE BLOOD FLOW.
AB  - The most important of this investigation has been the completion of various
      improvements in the construction and use of the plethysmograph, by means of which
      numerous errors attending the use of the instrument have been eliminated. The
      results of the work show that all olfactory sensations, so far as they produce
      any effect through the vasomotor system, tend to diminish the volume of the arm,
      and therefore presumably cause a congestion of the brain. Whenever the
      stimulation occassions an increase in the volume of the arm, as sometimes
      happens, it seems to be due to acceleration of the heart rate, which, of course,
      tends also to increase the supply of blood to the brain. The of odours varies in
      extent with different individuals, and with the same individual at different
      times. It was most marked in subjects sensitive to odours. Irritant vapours, such
      as formic acid, have a marked effect in the same direction-that is, they cause a
      strong diminution in the volume of the arm. The experiments give no support to
      the view that pleasant sensations are accompanied by a diminution of the See PDF
      for Structure blood supply to the brain and unpleasant sensations by the reverse
      efeect. In all my experiments mental work caused a marked and prolonged
      diminution in the volume of the arm. This vasomotor effect was sometimes preceded
      by a transitory increase in the volume of the arm caused by acceleration of heart
      rate.

PMID- 19866797
TI  - A STUDY OF THE BACILLUS (LEPTOTHRIX?) PYOGENES FILIFORMIS (NOV. SPEC.) AND OF ITS
      PATHOGENIC ACTION.

PMID- 19866798
TI  - OBSERVATIONS ON THE INNERVATION OF THE SUBLINGUAL AND SUBMAXILLARY GLANDS.

PMID- 19866799
TI  - A NEW METHOD FOR THE STUDY OF THE INTRACARDIAC PRESSURE CURVE.

PMID- 19866800
TI  - THE ROTARY PROPERTIES OF SOME VEGETABLE PROTEIDS.

PMID- 19866801
TI  - A CHEMICAL STUDY OF THE SECRETION OF THE ANAL GLANDS OF MEPHITIS MEPHITIGA
      (COMMON SKUNK), WITH REMARKS ON THE PHYSIOLOGICAL PROPERTIES OF THIS SECRETION.

PMID- 19866802
TI  - ON THE ACCELERATOR AND INHIBITORY NERVES TO THE CRAB'S HEART.

PMID- 19866803
TI  - A CASE OF CIRCUMSCRIBED UNILATERAL, AND ELECTIVE SENSORY PARALYSIS.

PMID- 19866804
TI  - ON THE PIGMENT OF THE NEGRO'S SKIN AND HAIR.
AB  - The pigmentary granules of the negro's skin and hair can be freed in several ways
      from the cells in which they are lodged and collected in any desired amount. As
      thus obtained, these granules are found to be insoluble in dilute alkalies,
      dilute hydrochloric acid (hot or cold), alcohol, or other organic solvents when
      applied in the order named. If, after they have been subjected to the action of
      dilute hydrochloric acid, they are again treated with dilute alkalies, they are
      found to give up their pigment, and, on the continued application of heat, the
      granules dissolve entirely in the alkaline solution, leaving only an
      insignificant residue. The pigmentary granules are composed of a colourless
      ground substance or substratum, a pigment, and much inorganic matter. Their
      inorganic constituents, as thus far determined, are calcium, magnesium, iron, and
      silicic, phosphoric, and sulphuric acids; and these constituents possibly play an
      important part in the deposition and fixation of the colouring matter in the
      granules. The pigment isolated from the granules, and sufficiently freed from
      adherent inorganic matter, contains only the merest trace of iron-so little, in
      fact, that we must think of it when entirely pure as free of iron. Heating the
      isolated pigment with barium hydrate at a temperature of 260 degrees C. entirely
      frees it from the closely adherent ground substance, and it is then found that
      the vapours of pyrrol are no longer emitted when it is subjected to dry
      distillation, and the odour of burnt feathers is no longer discerned, although
      nitrogen is still present. We can not conclude as the result of our work that the
      pigment is a derivative of haemoglobin; it seems to us more probable that it is
      ultimately derived from the proteids of the parenchymatous juices. The total
      quantity of soluble pigment in the skin of a negro of average size is found to
      weigh about 1 gramme; the weight of the pigmentary granules is about 3.3 grammes,
      if we are right in our assumption that they contain sixty-five per cent of water
      and five per cent of mineral constituents in their natural state in the
      epidermis. The pigments of the epidermis and hair of the negro are very likely
      identical. In the present state of our knowledge we can only say that it seems
      highly probable that the pigment of the negro's hair is not different from the
      dark pigment found in the hair of the white races, and we may infer that the
      pigment of the black skin differs only in amount and not in kind from that
      deposited in the skin of the white man.

PMID- 19866805
TI  - ON HAEMORRHAGIC CYSTS OF THE THYROID GLAND.
AB  - 1. All the features peculiar to the gross cysts of the thyroid gland which
      possess fluid contents appear to indicate that they are essentially of
      haemorrhagic origin. 2. While these gross cysts would seem more especially to
      occur in glands which already present the features of parenchymatous goitre, the
      theory of Wolfler that they originate as a consequence of spontaneous rupture of
      the vesicles is unsatisfactory. 3. It would seem more probable that these large
      cysts are due to rupture, traumatic or otherwise, of some of the vessels of the
      organ. The frequent signs of small haemorrhages in cases of parenchymatous goitre
      without evidence of associated gross change in the surrounding vesicles, the
      structure of the organ and its exposed position, all appear to favour this view.

PMID- 19866806
TI  - THE SIGNIFICANCE OF PATHOGENIC SPIRILLA IN AMERICAN SURFACE WATERS, WITH A
      DESCRIPTION OE ONE ISOLATED FROM THE SCHUYLKILL RIVER AT PHILADELPHIA.

PMID- 19866807
TI  - THE INFLUENCE OF ACUTE ALCOHOLISM ON THE NORMAL VITAL RESISTANCE OF RABBITS TO
      INFECTION.
AB  - THE DEDUCTIONS THAT MAY BE DRAWN FROM THE RESULTS OF THESE EXPERIMENTS ARE AS
      FOLLOWS: That the normal vital resistance of rabbits to infection by
      streptococcus pyogenes (erysipelatos) is markedly diminished through the
      influence of alcohol when given daily to the stage of acute intoxication. That a
      similar, though by no means so conspicuous, diminution of resistance to infection
      and intoxication by the bacillus coli communis also occurs in rabbits subjected
      to the same influences. And that, while in alcoholized rabbits inoculated in
      various ways with staphylococcus pyogenes aureus, individual instances of lowered
      resistance are observed, still it is impossible to say from these experiments
      that in general a marked difference is noticed between alcoholized and non
      alcoholized animals as regards infection by this particular organism. It is
      interesting to note that the results of inoculation of alcoholized rabbits with
      the erysipelas coccus correspond in a way with clinical observations on human
      beings addicted to the excessive use of alcohol when infected by this organism.
      In the course of the work an effort was made to determine if, through the
      oxidation of alcohol in the tissues to acids of the corresponding chemical group,
      the increase of susceptibility could be referred to a diminution in the
      alkalinity of the blood as a result of the presence of such acids. The number of
      experiments thus far made on this point is too small to justify dogmatic
      statements, but from what we have gathered there is but little evidence in
      support of this view. Throughout these experiments, with few exceptions, it will
      be seen that the alcoholized animals not only showed the effects of the
      inoculations earlier than did the non-alcoholized rabbits, but in the case of the
      streptococcus inoculations the lesions produced (formation of miliary abscesses)
      were much more pronounced than are those that usually follow inoculation with
      this organism. With regard to the predisposing influence of the alcohol, one is
      constrained to believe that it is in most cases the result of structural
      alterations consequent upon its direct action on the tissues, though in a number
      of the animals no such alteration could be made out by macroscopic examination. I
      am inclined, however, to the belief, in the light of the work of Berkley and of
      Friedenwald, done under the direction of Prof. Welch, in the Pathological
      Laboratory of the Johns Hopkina University, that a closer study of the tissues of
      these animals would have revealed in all of them structural changes of such a
      nature as to indicate disturbances of important vital functions of sufficient
      gravity to fully account for the loss of normal resistance. The conspicuous
      influence of the alcohol on the gastric mucous membrane in many of these animals,
      with the consequent disturbance of nutrition, is undoubtedly the explanation of
      the marked loss in body weight that was observed in many of the animals employed
      in these experiments. In this light the susceptibility induced by alcohol to
      excess is somewhat analogous to that induced by starvation, where we see the
      resistance of animals to particular forms of infection very markedly diminished.

PMID- 19866808
TI  - EXPERIMENTAL CONTRIBUTION TO THE STUDY OF THE PATH BY WHICH FLUIDS ARE CARRIED
      FROM THE PERITONEAL CAVITY INTO THE CIRULATION.

PMID- 19866809
TI  - ON ABSORPTION OF STRYCHNINE AND HYDROCYANIC ACID FROM THE MUCOUS MEMBRANE OF THE
      STOMACH.-AN EXPERIMENTAL STUDY ON RABBITS.

PMID- 19866810
TI  - THE PRODUCTION OF ANTITOXIN BY THE PASSAGE OF ELECTRICITY THROUGH DIPHTHERIA
      CULTURES.

PMID- 19866811
TI  - DIPHTHERIA ANTITOXIN SOMETIMES FOUND IN THE BLOOD OF HORSES THAT HAVE NOT BEEN
      INJECTED WITH TOXIN.

PMID- 19866812
TI  - THE INFLUENCE OF EXERCISE ON GROWTH.

PMID- 19866813
TI  - A STATISTICAL AND EXPERIMENTAL STUDY OF TERMINAL INFECTIONS.

PMID- 19866814
TI  - THE HISTOLOGIGAL LESIONS OF ACUTE GLANDERS IN MAN AND OF EXPERIMENTAL GLANDERS IN
      THE GUINEA-PIG.
AB  - The glanders nodule in the class of cases studied by us is in no sense analogous
      to the miliary tubercle in its histogenesis, and our studies afford no support to
      Baumgarten's views. The primary effect of the bacillus of glanders on a tissue we
      found to be not a production of epithelioid cells, which undergo necrosis and
      invasion by leucocytes, as happens in the cases in which the bacillus of
      tuberculosis is concerned, but to be the production of primary necrosis of the
      tissue, followed by inflammatory exudation, often of a suppurative character.
      Degenerative changes rapidly ensue in the inflammatory products. These
      conclusions are in harmony with the observations of Tedeschi, above referred to.

PMID- 19866815
TI  - TWO CASES OF SARCOMATOSIS WITH PURPURA HAEMORRHAGICA.
AB  - The purpura accompanying the two foregoing cases of sarcoimatosis would seem to
      find its explanation in the coexistence of several factors, the main feature
      being an involvement of the vascular system by the sarcomatous elements. There
      existed in Case I a direct lesion of the vessel wall whereby the sarcoma cells
      invaded directly the various coats, and were found mainly between the intima and
      the adventitia, dissecting their way, as it were, along these tracts in the
      vessel walls. There was further an extensive involvement of the perivascular
      lymphatics, from which point, indeed, it would seem that the sarcoma cells had
      invaded the walls of the vessels themselves. In Case II, moreover, not only was
      there a definite invasion of the lymph spaces near the vessels, but, furthermore,
      there was undoubted evidence of the existence of emboli of sarcoma cells in the
      lumina of the blood vessels; and in the immediate vicinity of such conditions
      haemorrhages were invariably found. While some vessels, and indeed a great many,
      were quite free from such emboli, in others the lumina were completely occluded
      by spindle cells, so as to preclude the possibility that these were merely a
      collection of desquamated endothelial cells, such as is frequently found as the
      result of post-mortem changes. That such an embolic condition can exist is by no
      means an unreasonable supposition, and, while it is generally recognised that
      multiple sarcomata are usually made up of small round cells, in this case we have
      an undoubted example of sarcomatosis of the spindle-celled variety. There are
      numerous instances of this " embolic purpura," as it may be called, especially in
      French and German literature, the condition being associated with rheumatism,
      valvular lesions of the heart, and other diseases which induce directly or
      indirectly the formation of emboli. Krauss, Gimard, Leloir, and others have
      insisted with considerable emphasis on the embolic origin of many purpuric
      conditions, and in some instances they have verified their observations by
      histological examination. Leloir assumes that, in addition to the presence of the
      ordinary emboli and the changes in the vessel walls with desquamative
      endarteritis, the blood itself may be much altered chemically, and that in the
      cachectic conditions clots may be thrown down from the circulating blood and be
      carried onward to form capillary emboli, with resulting haemorrhagic infarctions.
      Krogerer, some ten years ago, in examining the skin removed from patients with
      symptomatic purpura, found definite thromboses in the smaller veins, and even in
      the arteries. According to his view, the alterations in the vessel walls gave
      rise to slowed circulation and tendency to thrombosis, bringing about a liability
      to haemorrhages. His plates bear out his theories regarding the thrombi, many of
      which show considerable organization. But a careful examination of the purpuric
      areas shows further that a mere invasion of the vascular system by sarcoma cells
      can not explain all the various blood effusions present. On examining the skin,
      for instance, in those areas where large irregular haemorrhages had occurred,
      there was but little evidence of vascular invasion, while the emboli, on the
      other hand, seemed to exist mainly in the localized smaller and more
      circumscribed patches. One must therefore conclude that in such instances a
      combination of factors will alone afford a rational explanation of the purpura,
      and that in the general condition of the patient we shall find another cause for
      the enormous effusions of blood. In both of our cases there were high fever,
      cachexia, and a rapid progressive asthenia, all being the results of a
      sarcomatosis, and implying also grave alterations in the composition of the
      blood. From this we may infer an altered condition of the vessel walls, and hence
      probably a combination of circumstances sufficient to explain the incidence of
      haemorrhage. The raised cutaneous nodules in our second case, some of which were
      haemorrhagic, can not be regarded as pure sarcomatous metastases, for on
      microscopic examination they merely revealed haemorrhage or necrosis, or both,
      and sometimes plugging of the vessels. There was nowhere in these nodules
      evidence of new growths. Such elevations, then, must have been produced rather by
      a temporary serous or cellular exudation coincident with or following upon the
      haemorrhage-a probability which is emphasized by the fact that during the last
      days of the patient's illness many of the nodules diminished in size. Whether the
      oedema and infiltration were secondary to the embolic process in the subcutaneous
      vessels or whether they were merely coincident with the haemorrhage would be
      difficult to decide. The ringlike spots, however, are of special interest,
      inasmuch as it has been shown that they have been present in more than one case
      of sarcoma. It is not impossible that such spots may be definitely related either
      to the embolic processes or to a direct invasion of the cutaneous vessels,
      though, so far as we know, there do not exist any experimental proofs to bear out
      such a theory. From what has been said, however, it is evident that the cutaneous
      vessels were plugged during the last few days of the illness, at a time when the
      walls of the smaller vessels and capillaries were already greatly enfeebled. The
      result of the embolic formation may therefore mean a decided deficiency in the
      supply of nutriment to the involved area, the collateral circulation naturally
      being poor under the circumstances. As soon, then, as the vessels had become
      plugged, the surrounding blood supply would be poured in to a limited extent,
      and, on meeting the enfeebled vessels, might possibly break through their thin
      walls, thus producing a zone of haemorrhage around the area deprived of its
      normal nutrition. In other words, the condition may be regarded as in many
      respects analogous to that presented in embolic infarcts in regions with end
      arteries, central necrosis with peripheral congestion and haemorrhage being
      induced, the latter being chiefly limited to the outer zone of the necrotic area.
      The cutaneous vessels under such circumstances may be regarded as end arteries in
      a functional sense, since the collateral circulation would be so diminished under
      the altered conditions that no complete nourishment could be afforded to the area
      supplied normally by the plugged vessel. Von Recklinghausen has directed especial
      attention to the occurrence of cutaneous haemorrhages following embolic or
      thrombotic occlusion of peripheral arteries. The possibility of some toxic
      condition as a factor in the production of the purpura in our cases may also be
      suggested; but while we would not exclude this possibility, we are unable to find
      any positive evidence in its favour. Focal necroses, which are often associated
      with toxic and infectious processes, were present only in direct association with
      the haemorrhages, and were not distributed in the liver, spleen, and kidneys in
      the manner characteristic of toxic infections. Nevertheless the absence of these
      necroses does not exclude the possibility of the existence of some form of
      toxaemia. Infection demonstrable by bacteriological examination was absent, and
      there is no reason to regard our cases as allied to the infectious purpuras. The
      thermic theory suggested by Fagge at all events finds no place in the production
      of the multiple tumours in our cases, inasmuch as in each instance extensive
      visceral growths had given rise to the metastases.

PMID- 19866816
TI  - A STUDY OF THE CHARGES PRODUCED IN THE KIDNEYS BY THE TOXINS OF THE
      STAPHYLOCOCCUS PYOGENES AUREUS.

PMID- 19866817
TI  - INFLUENCE OF ACUTE ALCOHOL POISONING ON NERVE CELLS.

PMID- 19866818
TI  - OF THE ACTION OF ETHER ON CONTRACTURE AND OF POSITIVE KATHODIC POLARIZATION OF
      VERTEBRATE VOLUNTARY MUSCLE.

PMID- 19866819
TI  - THE REGENERATION OF THE BLOOD.
AB  - a. The blood of apparently normal animals undergoes considerable variations
      within physiological limits. b. After a loss of blood the regeneration is more
      rapid if there has been a transfusion of an artificial serum. c. Regeneration
      after transfusion is less rapid during the first half of the regeneration period
      than during the second half. d. The regenerative processes once stimulated into
      activity carry the blood, qualitatively, considerably beyond the established
      normal. (See Plate XXXIII.) Otto (2) observed a similar phenomenon. e. The
      quantity of haemoglobin per volume of red blood-corpuscles is not constant. f.
      The volume of red blood-corpuscles varies as the product of the average volume of
      individual corpuscles and the number of corpuscles per unit volume. (V
      proportional, variant v x n). g. When the number of the corpuscles increases the
      size decreases, and conversely, (n proportional, variant(1/2)). h. The quantity
      of haemoglobin varies in general with the number of red blood-corpuscles per unit
      volume. (Hb. proportional, variant n).

PMID- 19866820
TI  - A STUDY OF TYPES OF RESPIRATORY MOVEMENTS.
AB  - 1. Children of the two sexes differ very little in the character of their
      respiratory movements. 2. Between girls and women and boys and men there is
      little or no difference in respiratory type. 3. Childbearing does not permanently
      affect respiration. 4. The natural type of respiration, for both sexes is one in
      which the movement is fairly equally balanced between chest and abdomen, the
      abdominal being somewhat in excess. 5. In typical unconstricted individuals the
      chest contributes about the same bulk of air as does the abdomen. 6. Constricting
      dress causes preponderance of thoracic movement in ratio to its restriction of
      abdominal movement and to the sensitiveness of the nervous co-ordination.

PMID- 19866821
TI  - THE IMMUNIZING POWER OF NUCLEOHISTON AND OF HISTON.
AB  - THE RESULTS OBTAINED IN THE PRECEDING EXPERIMENTS MAY BE BRIEFLY SUMMARIZED AS
      FOLLOWS: 1. Nucleohiston does not protect against a separate and subcutaneous
      injection of tetanus toxin, diphtheria toxin, hog-cholera bacillus, or anthrax
      bacillus. 2. Mixtures of nucleohiston and either tetanus toxin or diphtheria
      toxin lose their specific toxic action-the latter much more rapidly than the
      former. Animals that recover after inoculation of such mixtures are not rendered
      immune. 3. In a mixture of nucleohiston and anthrax bacillus the latter is
      unaffected, even after the lapse of eleven days. 4. The destruction of specific
      toxins in a solution of nucleohiston, though in part due to sodium carbonate, is
      probably chiefly due to the nucleohiston. 5. Histon does not protect against a
      separate and subcutaneous injection of tetanus toxin, diphtheria toxin, hog
      cholera bacillus, or anthrax bacillus. 6. In a mixture of histon and diphtheria
      toxin the latter is destroyed in a few minutes. This action is in part, if not
      wholly, due to the acidity of the histon solution. Similar mixtures of closely
      related bodies, serum globulin or albumoses, in Witte's pepton, give analogous
      results. The animals that recover from such inoculations are not rendered immune.
      Histon does not destroy the tetanus toxin as readily as the diphtheria toxin. 7.
      Histon possesses decided and marked toxic properties which are not due to the
      hydrochloric acid present.

PMID- 19866822
TI  - ON THE PRESENCE OF NERVES IN TUMORS AND OF OTHER STRUCTURES IN THEM AS REVEALED
      BY A MODIFICATION OF EHRLICH'S METHOD OF "VITAL STAINING" WITH METHYLENE BLUE.

PMID- 19866823
TI  - THE INFLUENCE OF PHLORIDZIN ON THE BILE AND LYMPH.

PMID- 19866824
TI  - THE GELATIN FROM WHITE FIBROUS CONNECTIVE TISSUE.

PMID- 19866825
TI  - ON THE RELATION OF THE VOLUME OF THE CORONARY CIRCULATION TO THE FREQUENCY AND
      FORCE OF THE VENTRICULAR CONTRACTION IN THE ISOLATED HEART OF THE CAT.

PMID- 19866826
TI  - ON THE TIME OF REFLEX WINKING.
AB  - I. The mean total time taken from 450 experiments on sixteen subjects was found
      to be 0.0420 second. II. Natural winks occurring very shortly before the record
      was taken had no influence. III. The reflex time was found to vary in different
      individuals, the limits of the mean times being 0.0351 and 0.0491 second. For any
      given individual there was a close correspondence between averages of sets of
      experiments obtained under similar conditions. In the case of one man this was
      true of sets of experiments taken a year apart. Sex has no influence. IV.
      Apprehension seems to shorten the time.

PMID- 19866827
TI  - AN EXPERIMENTAL INVESTIGATION OF SOME OF THE CONDITIONS INFLUENCING THE SECRETION
      AND COMPOSITION OF HUMAN BILE.

PMID- 19866828
TI  - A RESEARCH UPON ANAESTHESIA.
AB  - THE CONCLUSIONS WHICH HAVE BEEN REACHED BY THE SERIES OF EXPERIMENTS RECORDED IN
      THE PRESENT MEMOIR ARE: First. Lowered arterial pressure has a comparatively
      feeble effect upon the respiration, but when the pressure falls sufficiently,
      respiratory depression does occur. Second. Even excessive lowering of blood
      pressure primarily stimulates the vaso-motor centre, the sensibility of the
      centre being evidently necessary to the automatic regulation of the circulation.
      Third. The circulation recovers itself more slowly after profound etherization
      than after a like chloroform narcosis. Fourth. It is possible for ether as well
      as chloroform to produce death some hours after the cessation of its
      administration, at a time when the cerebrum has long freed itself from distinct
      evidences of the narcotic, so that consciousness and intellectual action have
      been restored. In applying these conclusions to the subject of practical
      anaesthesia it is evident that the depression of the circulation produced by
      chloroform has effect upon the respiratory centres only when the pressure has
      fallen very low, and whilst it may be a factor in the production of respiratory
      failure during chloroformization, the failure must be chiefly due to the direct
      influence exercised by the drug upon the respiratory centres. Clinical experience
      shows that nausea and general depression are more pronounced after the use of
      ether than after the use of chloroform, a difference which is strongly insisted
      upon by the advocates of chloroform as an important agent in favor of that
      anaesthetic. Our research confirms clinical observation, and experimentally shows
      that the depression of the circulation produced by ether is more permanent than
      that caused by chloroform; the reason probably being the large amount of ether
      which is necessary to produce profound narcosis, with lowering of the arterial
      pressure; an amount so large that it can neither be burned up in the system nor
      yet eliminated in the time which would be necessary for the much smaller amount
      of chloroform to be gotten rid of after chloroformization.

PMID- 19866830
TI  - ON THE ACTIVE PRINCIPLE OF RHUS TOXICODENDRON AND RHUS VENENATA.

PMID- 19866829
TI  - EXPERIMENTS ON THE RELATION OF THE INHIBITORY TO THE ACCELERATOR NERVES OF THE
      HEART.
AB  - The experiments described in Part IV of this paper show that in whatever manner
      the problem of the relation of the vagus to the accelerators is approached,
      whether the accelerators are stimulated during a stimulation of the vagus, or the
      vagus during a stimulation of the accelerators, or both are stimulated
      simultaneously, either for a short or for a longer period, the result is the
      same, viz., the effect upon the rate of the heart is determined entirely by the
      relative strength of the stimuli applied to the two nerves. If the stimuli are of
      approximately the same strength, as judged by the effect of stimulating the
      nerves separately, the rate of the heart is but slightly affected; if the
      stimulus applied to the vagus is the stronger, the heart is slowed; if it is
      weaker, the heart is accelerated. In all cases the result of stimulating the two
      nerves simultaneously is approximately the algebraic sum of the results of
      stimulating them separately; sometimes the inhibitory effect slightly
      predominates, but not more frequently than does the accelerator effect. Moreover,
      the two nerves may be stimulated simultaneously for a considerable period of time
      without either completely overcoming the effect of the other. Thus as far as
      their effect upon the rate of the ventricular beat is concerned, the vagus and
      accelerator nerves seem to be purely antagonistic; the statement that a minimal
      stimulation of the one can completely overcome a maximal stimulation of the other
      is undoubtedly incorrect, and the hypotheses as to the mode of action of these
      nerves upon the heart, based upon this statement, lose their chief support.

PMID- 19866831
TI  - THE HISTOLOGICAL CHANGES PRODUCED BY RICIN AND ABRIN INTOXICATIONS.

PMID- 19866832
TI  - CHEMISTRY OF COLOSTRUM MILK; A REPORT OF SIX CASES.
AB  - Colostrum corpuscles are not always found in so-called colostrum milk; when they
      are present, the percentage of proteids is higher; as they disappear, the proteid
      percentage drops. The color of colostrum milk is yellow; this color is especially
      marked in negroes' milk (observed in four cases not included in this report). The
      reaction of colostrum milk is alkaline. The specific gravity varies from 1024 to
      1034. This variation is chiefly due to the variation in the amount of fat
      present.

PMID- 19866833
TI  - ON THE ACTION OF SUBSTANCES OF THE DIGITALIS SERIES ON THE CIRCULATION IN
      MAMMALS.
AB  - In summing up the contents of the preceding pages it may be stated that the
      action of digitalis has been divided into two stages according to the changes
      evinced by the ventricles under its influence; of these the first is
      characterized by marked inhibitory action together with modification of the
      cardiac muscle, while in the second the inhibitory action is less marked and the
      muscular action becomes the more prominent feature. The inhibitory action is due
      to direct stimulation by this series of the pneumogastric centrally in the
      medulla oblongata and peripherally in the heart. The extent to which the
      inhibitory mechanism is stimulated varies in different animals and with different
      members of the digitalis series. The muscular action of small quantities betrays
      itself in a tendency to increase the extent of the contraction, while in some
      cases the degree of relaxation reached in diastole is also lessened by it. In
      larger quantities the series increases the irritability of the cardiac muscle
      very considerably, and the spontaneous rhythm of the ventricles therefore becomes
      developed. Through the interaction of these two factors in the first stage the
      rhythm of the whole heart is slowed, the contraction of the ventricle is more
      complete, and the diastolic relaxation is generally increased, although it may be
      unchanged or lessened. The systolic pressure is increased and the fall from
      maximum to minimum pressure is slower than normal owing to the increased
      completeness and longer duration of systole (Rolleston). The auricles generally
      contract with less force and may relax more completely than normally. Sometimes,
      however, their contractions also are more complete than before the injection of
      the drug. This latter condition generally precedes the diminution of the force of
      the auricular contraction. This variation of the effects of digitalis in the
      auricle explains the changes in intra-auricular pressure noted by Kaufmann. The
      contraction volume of the ventricles is always much increased, and the output per
      unit of time is generally augmented, and this together with the contraction of
      the peripheral arterioles causes an increase in the tension in the systemic
      circulation, an acceleration of the circulation, and possibly a temporary
      increase in the pressure in the great veins and in the auricle and ventricle in
      diastole (Kaufmann). The pressure in the pulmonary artery is practically
      unaffected by some members of the series, while by others it is considerably
      increased. This difference in the reaction of the pulmonary circulation is due to
      the varying extent to which these drugs act on the peripheral arteries and not to
      any difference in their action on the two sides of the heart. If the inhibitory
      action be very strongly marked the slowing of the heart may be extreme, the
      ventricles assuming their own spontaneous rhythm and all connection with the
      auricles being lost. While the contraction volume of the ventricle is still
      greater than normal, their output per unit of time may become less than normal,
      the aortic tension therefore fall and the rapidity of the circulation be
      lessened. The ventricles maintain their association throughout, and probably the
      rhythm of the two auricles also remains equal. The ventricular rhythm, however,
      becomes irregular owing to the variation in the duration of the diastolic pause.
      The auricles may cease altogether in diastole, or may continue to beat with a
      slower or faster rhythm than the ventricles. During the second stage the rhythm
      of the heart becomes accelerated owing to the increased irritability of the heart
      muscle. The ventricle tends to assume a rapid spontaneous rhythm, while the
      auricular rhythm is also quicker than in the first stage. When these two rhythms
      interfere by the passage of impulses across the auriculo-ventricular boundary in
      either direction, irregularity of the heart is produced, generally bearing a
      distinctly periodic character. The ventricles continue to maintain their common
      rhythm, while the auricles and ventricles may contract at quite different rates.
      The two ventricles, however, do not necessarily contract with equal force, and
      the contractions of one may present periodic variations in strength, while those
      of the other may be almost perfectly uniform. The contractions of the auricles
      vary in the same way as regards each other and the ventricles. The inhibitory
      nerves are no longer able to slow the ventricular rhythm, but may affect the
      completeness of systole and diastole in the ordinary way. The auricular
      contractions can still be lessened in force and possibly be abolished by their
      stimulation, and the impulses passing between the auricle and ventricle may
      therefore be blocked and regularity of the heart produced by powerful inhibition.
      The irregularity of the contractions is therefore due indirectly to the increased
      irritability of the cardiac muscle and the acceleration must be attributed to the
      same cause. An extreme phase of this stage produced by the interference of the
      rhythms is a temporary standstill of one of the chambers, generally the auricle.
      The irregularity leads to a lessened efficiency of the work of the heart. The
      output varies extremely in successive observations and the contraction volume of
      every individual beat may differ. The various chambers often show a tendency to
      dilate during this stage. The blood pressure in the systemic arteries at first
      remains high, in fact may be higher than in the first stage owing to the
      increased rapidity of the heart rhythm, but afterwards falls continuously as the
      periodic variations become shorter in duration. The auricles generally cease
      contracting before the ventricles, but not invariably. There is no fixed order in
      the cessation of the ventricles or auricles. Each division comes to a standstill
      in a position somewhat nearer diastole than systole and then passes into delirium
      and dilates to the fullest extent.

PMID- 19866834
TI  - A GRAPHIC STUDY OF TREMOR.
AB  - FROM OUR OBSERVATIONS I THINK THE FOLLOWING PROPOSITIONS ARE JUSTIFIED: (1) All
      muscular movements are made up of a series of elementarycontractions and
      relaxations in alternation, which may be appreciable as tremor in conditions of
      both health and disease. (2) The differences between different tremors are of
      degree rather than of kind, i. e. no one form of tremor is distinctive of any one
      disease or group of diseases. (3) No definite relation exists between one form of
      tremor and any other. (4) The frequency of movement is in inverse ratio to the
      amplitnde and vice versa. (5) Habitual movements are performed with greater
      freedom from tremor than unusual movements. (6) There is no material difference
      between the movements of the two sides of the body, except as related to
      Proposition (5).

PMID- 19866835
TI  - A CONTRIBUTION TO THE PHYSIOLOGY OF SLEEP, BASED UPON PLETHYSMOGRAPHIC
      EXPERIMENTS.

PMID- 19866836
TI  - NODULAR FORMS OF TUBAL DISEASE.
AB  - THE CONCLUSIONS AT WHICH WE ARRIVE ARE THE FOLLOWING: 1. Nodular enlargement of
      the tube can be caused by a number of different pathological conditions. 2.
      Clinical examination does not enable us to make a diagnosis of the pathological
      condition existing in an individual case of nodule of the tube. 3. The diagnosis
      of the nature of a tubal nodule can be made only with the microscope. 4. The
      conditions causing nodular enlargement of the tube are congenital or acquired,
      non-inflammatory or inflammatory. 5. Any one of these conditions can exist
      without the production of nodules. 6. The nodules can be found in all parts of
      the tube and-taking the peculiar anatomy of each part of the tube into account
      show the same structure. 7. The enlargement can be caused by epithelial or
      epithelioid formations, connective or muscular tissue, by round-cell
      infiltrations or combinations of two or more of these. 8. The epithelial
      formations originate in the epithelium of a. the tubal mucous membrane
      (salpingitis pseudo-follicularis, adenomyoma originating in the tubal
      epithelium). b. the accessory tubes (intraparietal parasalpinx and hydro
      parasalpinx). c. remnants of the Wolffian body (adenomyoma). 9. The epithelioid
      formations originate in the peritoneal endothelium (peritoneal growths under
      "relative heterotopy"). 10. The excess of formation of connective tissue is a
      consequence of inflammatory conditions of the tubal wall (salpingitis
      interstitialis, Zweifel). 11. The hypertrophy of the muscular tissue is a. non
      inflammatory (adenomyoma). b. consequent upon inflammation-Kaltenbach's case
      (23). 12. The accumulations of round cells are direct evidence of inflammation:
      a. non-specific (salpingitis interstitialis disseminata, salpingitis abscedens);
      or b. specific (salpingitis tuberculosa or s. gonorrhoica). 13. The epithelioid
      formations can occur wherever pseudo-membranes cover organs lined with a serous
      coat. 14. Extra-uterine pregnancy (abdominal or tubal) produces epithelioid
      formations by causing pseudo-membranes to form-not by any irritation peculiar to
      the pregnancy.

PMID- 19866837
TI  - ON THE CAUSE OF THE HEART BEAT.
AB  - 1. The cause of the rhythmic contraction of the ventricle lies within the
      ventricle itself. 2. The cause of the rhythmic contraction is not a single,
      localized, co-ordination centre; the co-ordination mechanism, whatever it may be,
      is present in all parts of the ventricle. 3. The integrity of the whole ventricle
      is not essential to the coordinated contractions of a part of the ventricle. 4.
      The apex of the mammalian heart possesses spontaneous, rhythmic contractility. 5.
      Assuming that the general belief in the absence of nerve cells from the apical
      part of the ventricle is correct, these experiments demonstrate that nerve cells
      are not essential to spontaneous, long-continued, co-ordinated contractions of
      the ventricle.

PMID- 19866838
TI  - A STUDY OF METABOLISM DURING FASTING IN HYPNOTIC SLEEP.

PMID- 19866839
TI  - ON THE OCCURRENCE OF THE FAT-SPLITTING FERMENT IN PERITONEAL FAT NECROSES AND THE
      HISTOLOGY OF THESE LESIONS.

PMID- 19866840
TI  - A CASE OF DOUBLE TERATOMA.

PMID- 19866841
TI  - alpha-METHYL-QUINOLINE AS A CONSTITUENT OF THE SECRETION OF THE ANAL GLANDS OF
      MEPHITIS MEPHITICA.

PMID- 19866842
TI  - A FURTHER EXPERIMENTAL CONTRIBUTION TO THE KNOWLEDGE OF THE MECHANISM OF
      DEGLUTITION.

PMID- 19866843
TI  - ON THE PRESENCE OF THE AMYLOLYTIC FERMENT AND ITS ZYMOGEN IN THE SALIVARY GLANDS.

PMID- 19866844
TI  - ON THE PRESENCE OF A MILK-CURDLING FERMENT (PEXIN) IN THE GASTRIC MUCOUS MEMBRANE
      OF VERTEBRATES : A SUMMARY OF EXPERIMENTS MADE IN THE BIOLOGICAL LABORATORY OF
      BRYN MAWR COLLEGE BY CAROLINE W. LATIMER, M. D., ANNE C. COLEMAN, B. A., AND
      ROSALIE A. FURMAN, B. A.

PMID- 19866845
TI  - NOTE ON THE INFLUENCE OF "PEPTONE" ON THE CLOTTING OF MILK BY RENNET.

PMID- 19866846
TI  - A STUDY OF THE VISCERAL CHARGES IS EXTENSIVE SUPERFICIAL BURNS.

PMID- 19866848
TI  - ON CERTAIN IMPROVEMENTS IN HISTOLOGICAL TECHNIQUE : I. A DIFFERENTIAL STAIN FOR
      AMOEBAE COLI. II. PHOSPHOTUNGSTIC-ACID-HAEMATOXYLIN STAIN FOR CERTAIN TISSUE
      ELEMENTS. III. A METHOD OF FIXATION FOR NEUROGLIA FIBRES.

PMID- 19866847
TI  - ON THE APPEARANCE OF CERTAIN AMOEBOID BODIES IN THE BLOOD OF VACCINATED MONKEYS
      (RHOESUS) AND CHILDREN, AND IN THE BLOOD FROM CASES OF VARIOLA : AN EXPERIMENTAL
      STUDY.
AB  - 1. The claim of L. Pfeiffer that small granular amoeboid bodies are present in
      the blood of vaccinated children and calves, and in the blood from cases of
      variola, during the stage of fever is confirmed. A nucleus has not been
      positively made out in any of these bodies. 2. Granular amoeboid bodies, having a
      diameter about one-third that of a red blood cell, appear, also, in the blood of
      the monkey during the active stage of vaccinia and disappear with the decline of
      the local inflammation. 3. A body of like appearance, granulation and size may
      occasionally be found in the normal blood of monkeys and children. 4. Pale
      amoeboid bodies, containing a few dark pigment-like granules, are present in the
      blood from cases of variola and in the blood of the variolated monkey. Bodies of
      like appearance may occasionally be found in the blood of vaccinated children and
      monkeys.

PMID- 19866849
TI  - FURTHER STUDIES UPON THE PATHOGENIC SPIRILLA OF THE SCHUYLKILL RIVER AT
      PHILADELPHIA.

PMID- 19866850
TI  - A MODIFICATION OF THE METHOD FOR DETERMINING THE PRODUCTION OF INDOL BY BACTERIA.

PMID- 19866851
TI  - THE INFLUENCE OF ENVIRONMENT UPON THE BIOLOGICAL PROCESSES OF THE VARIOUS MEMBERS
      OF THE COLON GROUP OF BACILLI : AN EXPERIMENTAL STUDY.
AB  - Assuming the typical colon bacillus and the typical typhoid bacillus to represent
      the types of this group that present the greatest divergences in biological
      peculiarities, we conclude, as others also have done, that there is a series of
      closely related forms that may be regarded as intermediate or transitional and
      which serve to establish a biological relationship, either near or remote,
      between these two typical members. From our own studies we are inclined to regard
      the typical colon bacillus as the type of this group, for the reason that its
      functional equilibrium, as observed in the intestine, is so permanent a quality
      that it may readily be perpetuated under what is ordinarily regarded as favorable
      artificial circumstances, and that with the continuance of such conditions there
      is no conspicuous tendency on the part of this organism to deviate from what we
      regard as its norm; whereas, on the other hand, with all the other members of
      this group with which we have worked, there is not only a lack of uniformity in
      the adjustment of the functions, but such as exists is readily disturbed under
      artificial environment; though it must be borne in mind that even with the
      typical colon bacillus we have also shown functional modifications to be possible
      under particular conditions. When the members of the colon group are cultivated
      under circumstances favorable to the development of both the function of
      fermentation and that of proteolysis, fermentation invariably takes precedence
      and no evidence of proteolysis is manifested until after fermentation has ceased.
      The cultivation of all the members of the colon group under circumstances that
      favor the development of one function, viz. that of proteolysis, at the expense
      of another, viz. that of fermentation, results first in an apparent increase of
      vigor; but this is of temporary duration and is quickly followed by the decline
      and death of the cell. The result of this increased activity of the proteolytic
      function is the formation of much larger amounts of indol by typical colon
      cultures than has ever been obtained by us by any other method. By the method of
      experimentation through which we were enabled to accentuate the proteolytic
      activity of the typical colon bacillus, as caused by an increase of indol
      formation, we have also induced the function of indol formation not only in
      atypical colon bacilli that had been devoid of it, but in every specimen of
      typical typhoid bacilli to which we had access as well. We feel justified in
      regarding one of the differential tests between the typhoid and colon bacillus,
      namely that of indol formation on the part of the latter and the absence of this
      function from the former, as of questionable value, for the reason, as shown
      above, that by particular methods of cultivation indol production has been shown
      to accompany the development of a number of specimens that we have every reason
      to regard as genuine typhoid bacilli. As a result of our own experiments,
      together with the observations of others, there can be no doubt that the bacillus
      coli communis at times possesses pathogenic properties, and that by artificial
      methods of treatment it may often be brought from a condition of benignity to one
      of virulence. The spleen of a typhoid patient has always been regarded as the
      only trustworthy source from which to obtain the typical typhoid bacillus. While
      we believe this to be true, still our investigations show that other members of
      the colon group may also be present in this viscus; in fact, from such spleens we
      have isolated practically all of the varieties of this group with which we are
      acquainted. From our experience, the value of the serum test for the
      differentiation of typhoid and colon bacilli would seem to be questionable. We
      are inclined, however, to attribute the irregularities recorded above as due more
      to the method of application than to defects of the principles involved; for, as
      stated, by the use of dried blood, as in our experiments, it is not possible to
      make the test with constant and accurate, or even approximately accurate,
      dilutions of the serum. Our irregularities may be in part due to this defect. We
      therefore lay less stress upon this than upon the other features of our work.

PMID- 19866852
TI  - A STUDY OF THE ACTION OF ACONITIN ON THE MAMMALIAN HEART AND CIRCULATION.
AB  - The action of aconitin on the dog's heart, therefore, seems to consist in: 1. A
      stimulation of the inhibitory mechanism, especially of the centres in the medulla
      oblongata. 2. An increase in the irritability of the muscle of the auricle and
      the ventricle, which leads to independent contractions of one or both of these
      divisions and culminates in fibrillary contractions in the ventricle. The first
      of these is the only effect seen in the therapeutic use of the drug, and aconitin
      may, therefore, be considered to be indicated when it is desirable to stimulate
      the inhibitory centre without acting on the heart muscle. Of course it has a
      further effect on the circulation through the stimulation of the vaso-motor
      centre, but this would appear to be of minor importance.

PMID- 19866853
TI  - ANATOMICAL FINDINGS IN A CASE OF FACIAL PARALYSIS OF TEN DAYS' DURATION IN A
      GENERAL PARALYTIC, WITH REMARKS ON THE TERMINATION OF THE 'AUDITORY' NERVES.

PMID- 19866854
TI  - A CONTRIBUTION TO THE STUDY OF HUMAN NEUROGLIA.
AB  - THE RESULTS AND CONCLUSIONS OF THE ABOVE INVESTIGATION ARE: 1. The term glio
      sarcoma should be dropped, as unscientific and misleading in its significance. 2.
      The problems regarding neuroglia demand varied methods for their adequate study.
      3. With all the means at our command, the absolute determination of the relation
      of cells and fibres in individual cases remains difficult and at times
      impossible. 4. No criterion has yet been offered to determine a fundamental
      distinction between glioma and sarcoma (Stroebe); and secondly, between glioma
      and so-called gliosis (Weigert). 5. The development of neuroglia in all
      probability is from cells with protoplasmic processes to cells with
      differentiated and independent fibres. 6. Herein lies a possible reconciliation
      of the conflicting views concerning the ultimate structure of human neuroglia.

PMID- 19866855
TI  - THE CLINICAL COURSE AND PATHOLOGICAL HISTOLOGY OF A CASE OF NEURO-GLIOMA OF THE
      BRAIN.

PMID- 19866856
TI  - FOCAL OR INSULAR NECROSIS PRODUCED BY THE BACILLUS OF TUBERCULOSIS.
AB  - 1. It must be accepted from a comparison between the histological changes
      described in the focal necroses due to abrin and ricin, diphtheria, eclampsia,
      blood-serum intoxication, typhoid fever, lobar pneumonia and glanders, and those
      described here in three cases of tuberculosis, that the last are also instances
      of focal necrosis. 2. It may be claimed that the areas of necrosis in the three
      cases of tuberculosis had their origin in ischaemia, for the reason that they
      were numerous in the spleen and were not found in the kidney. Against such an
      explanation of their causation are the facts: that other forms of necrosis affect
      frequently the spleen and seldom the kidney; that thrombosis of vessels or any
      fixed relation of the areas in the spleen to blood-vessels could not be
      established; that the tubercle bacilli were invariably present; and lastly and of
      no slight importance, that these necroses were all present in cases of marked
      marasmus. 3. That the areas of necrosis in these three cases might be phenomena
      resulting from a mixed infection with pyogenic bacteria is possible, but no
      groups, colonies or even single bodies could be found which answered to the
      requirements in shape or staining properties for such bacteria. Even were it the
      case that the focal necroses here presented are the histological lesions of a
      septicaemia occurring as a complication of tuberculosis, the presence of the
      bacillus of tuberculosis in the areas of necrosis would still require
      explanation. 4. Lastly, it is not unreasonable to suppose that a diminished
      resistance on the part of the tissues incidental to marasmus is an important
      factor in the production of these necrotic lesions.

PMID- 19866857
TI  - TECHNICAL NOTE : I. A MODIFIED FIXING FLUID FOR GENERAL HISTOLOGICAL AND NEURO
      HISTOLOGICAL PURPOSES. II. A STAINING COMBINATION OF GENTIAN VIOLET AND PICRO
      ACID FUCHSIN.

PMID- 19866858
TI  - ON A METHOD OF ISOLATING AND IDENTIFYING BACILLUS TYPHOSUS, BASED ON A STUDY OF
      BACILLUS TYPHOSUS AND MEMBERS OF THE COLON GROUP IN SEMI-SOLID CULTURE MEDIA.
AB  - Semi-solid culture media, and more especially media rendered semi-solid by
      temperatures of from 30 degrees to 40 degrees C., seem to have an important
      bearing in the differentiation of bacterial species, particularly those
      presenting various degrees of motility. In such media not only the effect of
      differences in consistence on the motility of an organism may be noted, but the
      effect produced by various chemicals and nutrient ingredients on the growth and
      motility may be readily observed. By systematically varying the constituents of
      such media it has been possible to produce a medium in which the behavior of
      Bacillus typhosus differentiates it from the various members of the colon group;
      and also to produce a medium in which the colonies of Bacillus typhosus assume a
      form which distinguishes them from the colonies of the colon bacilli in plate
      cultures. Bacillus typhosus alone of all the organisms investigated during these
      experiments has displayed both the power of giving rise to thread-forming
      colonies in the plating medium and that of the uniform clouding of the tube
      medium, hence these two characters may prove to be of great value in the
      identification of this organism. The practical application of the use of these
      media has led to the ready detection of Bacillus typhosus and its isolation from
      the stools of patients suffering from typhoid fever. No suspected water has been
      subjected to test, but from the investigation of artificially infected tap-water
      the media here described may be assumed to have an application in the detection
      of Bacillus typhosus in such waters.

PMID- 19866859
TI  - THE BACTERICIDAL ACTION OF LYMPH TAKEN FROM THE THORACIC DUCT OF THE DOG.

PMID- 19866860
TI  - NOTES ON THE PHYSIOLOGY OF THE CARDIAC SERVES OF THE OPOSSUM: (DIDELPHYS
      VIRGINIANA).

PMID- 19866862
TI  - FIBRINOUS EXUDATES AND FIBRINOID DEGENERATION.

PMID- 19866861
TI  - NOTE ON THE PHYSIOLOGY OF THE CARDIAC NERVES OF THE CALF.

PMID- 19866863
TI  - NOTES ON THE PATHOLOGICAL CHANGES IN THE ORGANS OF BIRDS INFECTED WITH
      HAEMOCYTOZOA.

PMID- 19866864
TI  - ON THE HAEMATOZOAN INFECTIONS OF BIRDS.

PMID- 19866865
TI  - PRELIMINARY OBSERVATIONS ON A CASE OF PHYSIOLOGICAL ALBUMINURIA.
AB  - 1. The proteids consisted of albumins and globulins, varying in quantity between
      the extremes of .9010 grm. and .2592 grm. in the 24 hours, but usually between .7
      and .37 grm., the average being .5317 grm. 2. The quantity of the proteids varies
      directly as the urea, inversely as the external temperature. The relation between
      the quantity of urine and the quantity of proteid is not constant. The quantity
      of the proteida is little affected by diuretics; it tends to be increased by
      certain drugs that act upon the circulation. It is lessened during sleep. It is
      apt to suffer a sudden temporary increase, returning as suddenly to the usual
      average. For this phenomenon we have no explanation. 3. From .5449 to .6616 grm.
      of coagulable proteids a day (.0079 to .0094 grm. per kilo of body-weight) may be
      excreted through the urine for an indefinite time by an otherwise healthy
      individual without damage to either kidneys or organism.

PMID- 19866866
TI  - THE FATE OF THE GIANT CELLS IN HEALING TUBERCULOUS TISSUE, AS OBSERVED IN A CASE
      OF HEALING TUBERCULOUS MENINGITIS.
AB  - From the foregoing description of the histological changes in the leptomeninx it
      is quite evident that we are dealing with a chronic, stationary, healing form of
      tuberculous inflammation. This statement is substantiated, in the first place, by
      the clinical history. The only reasonable interpretation of the symptoms would
      establish the duration of the process as four months. The imaginable contingency
      that there existed first a meningeal syphilitic lesion that was dispersed by the
      iodide of potassium only to be followed by a tuberculous infection is so remote
      and unlikely that it need not be discussed. At all events the tuberculous
      leptomeningitis, which presented a typical distribution, began insidiously,
      existed at times in a latent condition, and pursued a very anomalous course,
      marked by a relative mildness of all the symptoms, and thus it came about that
      when an apparent or real improvement followed the administration of iodide of
      potassium able observers were induced to make an erroneous diagnosis. Death
      occurred as a result of an intercurrent infection. The long duration of the
      process is also shown, anatomically, by the thick layer of firm, translucent and
      gelatinous material that matted together the structures at the base, and also by
      the evident adhesions between the pia and the brain. The histological examination
      furnishes proof positive of the correctness of the conclusion in regard to the
      peculiar character of this process because it shows: (1) That the tuberculous
      proliferation is uniform in development and has reached nearly the same stage of
      evolution throughout the entire extent of the leptomeninx involved; it is not a
      process that has advanced by exacerbations and irregular extensions; the lesions
      are, generally speaking, of nearly the same age everywhere and must have begun at
      about the same time. (2) That only a very limited degree of caseous degeneration
      is present, pointing to an early arrest of the activity of the tubercle bacillus
      or to a very decided diminution or attenuation of its virulence. (3) That the
      subendothelial intimal proliferations of epithelioid cells, so generally found in
      acute tuberculous leptomeningitis,* have in this case become more or less
      completely changed into distinct fibrous tissue in which but very slight, if any,
      direct evidence of its tuberculous origin can be found. It is only by recognizing
      that the chronic endarteritis is most marked in correspondence with the most
      advanced adventitial tuberculous changes, and by finding an imperfect, much
      altered giant cell in one district of intimal thickening, that we were able to
      establish the direct kinship of the endovascular changes with those of the pia in
      general. (4) That acute inflammatory changes, in the form of emigration of
      polymorphonuclear leucocytes and of fibrinous exudation, are entirely absent in
      all parts of the district involved. The presence of a turbid serous fluid is of
      course not at all inconsistent with the view that the anatomical changes are of
      long duration. (5) That the granulation tissue present is, in general, undergoing
      fibrillation and contains a rich supply of enabryonal capillary vessels as well
      as of larger blood-vessels of evidently new formation. The absence of any
      considerable extent of polymorphonuclear leucocytic infiltration in this tissue
      has already been referred to. The cells in the granulation tissue correspond to
      the cells of embryonal or formative connective tissue. Vacuolation is rarely
      present. (6) That the unusually large number of giant cells present are
      remarkably free from evidences of necrosis and degeneration of the character
      ordinarily observed in tuberculous proliferations, that they do not contain in
      demonstrable form tubercle bacilli, and that the majority of the giant cells seem
      to be separating into individual cells and smaller masses often with, but
      sometimes also without, evidences of nuclear disintegration. The possibility that
      these phenomena may signify fusion instead of the sundering of cells will be
      discussed below. For these reasons there can be no doubt that the general claim
      that we are dealing with an instance of chronic, healing tuberculous meningitis
      must be regarded as established beyond dispute. The growth of tubercle bacilli in
      the glycerine-agar tubes, inoculated with the fluid from the pial meshes, and the
      demonstration of tubercle bacilli, though in very small numbers, between the
      cells of the embryonal tissue, furnish the positive evidence that we are actually
      dealing with a tuberculous process due to living and not to dead bacilli. The
      degree of virulence of the cultures of tubercle bacilli was, unfortunately
      perhaps, not studied. The presence of living tubercle bacilli in a tissue free
      from active and acute changes characteristic of tuberculosis demonstrates that,
      whatever the actual degree of virulence of the bacilli may have been, the tissue
      in which they were found was at this time relatively immune from their action.
      The manner in which this immunity was produced, and in which the process of
      healing was initiated, need not be discussed at this time any further than to
      again direct attention to the fact that the bacilli lost their virulency as
      regards the cells in this leptomeninx before these cells underwent any marked
      degree of degeneration. The cells of the tuberculous proliferations survived the
      further action of the bacilli whose original effect it was to initiate cell
      accumulation or proliferation; the cells also retained sufficient vitality to
      develop, in some instances at any rate, into formative cells according as their
      origin would dictate, e. g. into fibroblasts. That fibroblasts are formed only by
      embryonal connective tissue cells, and not by wandering cells, such as the large
      mononuclear leucocytes, we are well aware, is possibly still a disputable
      assumption, and we do not consider it pertinent to discuss the question any
      further in connection with this study, but would only emphasize the point that
      some of the cells of tuberculous proliferations may, under favorable
      circumstances, become formative cells, and, furthermore, that the amount of
      formative tissue produced may be far in excess of what is actually needed for
      purposes of repair only. Surely the appearances here noted indicate that the
      bacillus of tuberculosis has the power to stimulate fixed cells to multiply,
      unless one assumes that all, or almost all, the formative cells here seen are
      derived from wandering cells attracted by the presence of the bacillus and its
      products. As to the ultimate fate of the formative and other cells in this
      healing tuberculous tissue no final statements can be made. It must be remembered
      that it is only one stage in the process of healing that is dealt with. The well
      marked evidences of fibrillation, the quite extensive formation of new vessels,
      the absence of evidences of degenerative changes in the uninuclear cells, all
      point to the production of new fibrous tissue as sure to occur, but it seems
      quite probable that occasional epithelioid cells may undergo or have undergone
      dropsical or other forms of degeneration, although it is certainly apparent that
      so far as the small cells are concerned the involution of the tuberculous tissue
      is not occurring through disintegration. Perhaps the most interesting feature in
      this case is the opportunity it affords to study the changes in the giant cells
      of healing, non-degenerated tuberculous tissue. In the first place, the large
      number of giant cells is quite remarkable. The general characters of the tissue
      in which they are found recall the fact that giant cells are regarded as quite
      constant elements in chronic mild tuberculosis; often the giant cells are the
      only cells that contain bacilli (Koch). In this instance the giant cells do not
      contain bacilli that are demonstrable by the usual methods; neither do they
      contain bodies that can be definitely interpreted as degenerate forms of bacilli
      such as those found by Metchnikoff, Stchastny, Weicker, and others, in the giant
      cells of Spermophilus guttatus, in avian and in human tuberculosis. Metchnikoff
      states, however, that he knows of the occurrence of such degenerate forms only in
      the Spermophilus guttatus under the circumstances mentioned, and in the rabbit
      and guinea-pig in mammalian tuberculosis, but not in man; consequently, the
      manner in which the giant cells rid themselves of the bacilli undoubtedly present
      in their interior at some time during their existence, must as yet remain without
      any explanation. In the description of the histological changes the various
      appearances presented by the giant cells are described somewhat minutely. The
      essential observations made concern, in my opinion, the further fate of giant
      cells which are still found to persist in healing nondegenerated tuberculous
      tissue. It was, I believe, quite conclusively shown that the consecutive changes
      appear to consist in the breaking up of the nuclei, the removal of the detritus
      by phagocytes, and the formation of a few apparently viable uninuclear cells in
      the case of more degenerated, exhausted giant cells, while other, and, as it
      would seem, better preserved or younger giant cells, separate into a number of
      individual, uninuclear cells with but little or no nuclear disintegration.
      Objection might be raised to this interpretation of the appearances in the giant
      cells. While no one could very well dispute the view that part of the giant cells
      are undergoing retrogressive and absorptive changes with the production of some
      viable cells, a question might well be raised concerning the nature of the
      process taking place in those giant cells that have been spoken of as splitting
      up or dividing into uninuclear cells and smaller multinucleated masses without
      much evidence of nuclear disintegration. (ABSTRACT TRUNCATED)

PMID- 19866867
TI  - A CASE OF PSEUDO-LUPUS VULGARIS CAUSED BY A BLASTOMYCES.
AB  - The case reported, in this article is one of a somewhat extensive cutaneous
      disease, which occurred in a man, 33 years of age, who gave the following
      history: The disease first made its appearance, eleven and a half years ago, at
      the back of the left ear, as a pimple which soon became pustular. The process
      extended forward, very slowly and gradually encroached upon and covered almost
      the entire face, the central portion of which now presents an atrophic
      cicatricial condition. Another similar lesion occurred, one month after the
      primary invasion, on the back of the hand, which healed in about four years,
      after treatment with caustic. A third lesion appeared on the right side of the
      scrotum (six months after), which increased in size for a year and then healed
      spontaneously. A fourth inoculation appeared, on the anterior surface of the left
      thigh just above the internal condyle, and grew for a year, after which it
      gradually healed spontaneously. A fifth lesion appeared on the back of the neck
      and also healed spontaneously after growing for a year. The disease when first
      examined presented many of the features of a lupus vulgaris. There were no
      enlarged lymphatic glands and the patient's health had always been good. The
      family and personal history revealed no syphilitic or tuberculous taint. Sections
      from the cutaneous lesions showed the presence of what appeared to be budding
      blastomycetes. The sections also presented pathological features similar to those
      seen in the first case recorded by Gilchrist; in many sections almost typical
      tubercles were found. The organisms in the tissue are chiefly spherical,
      unicellular bodies varying from 10-20 micro in diameter, and consist of a doubly
      contoured membrane, which encloses a fine granular protoplasm with sometimes a
      vacuole. Many budding forms in various stages were found; nonucleus could be
      demonstrated, neither were any mycelium or hyphae present in the tissues. The
      parasites were almost always found outside of cells, comparatively few being
      enclosed in giant cells. Pure cultures of the organism were obtained directly
      from the cutaneous lesions in two places from the pus squeezed out from between
      the papillomatous variety of the lesion. The organism grew on all ordinary media,
      and especially well on potato and beer-wort agar. The cultures showed both
      budding forms and a fairly profuse mycelium. Older cultures, carried through many
      generations, produced sometimes little or no mycelium. The organisms in the
      cultures were round, ovoid, doubly contoured, refractive bodies, varying in size
      from about 10 to 20micro in diameter. The mycelium was, on rare occasions, of two
      varieties, very fine and also coarse with sessile buds and conidia. Dogs, a
      horse, a sheep and guinea-pigs were successfully inoculated, the most striking
      results being nodules, grossly simulating tumors, in the lungs. Microscopically
      these nodules were of a chronic inflammatory nature and contained numerous
      parasites identical in appearance with those in the patient. In the tissues of
      none of the animals successfully inoculated was any mycelium found. Since our
      organism did not ferment sugar and produced in cultures mycelium, it may either
      belong to the blastomycetes or to the oidia, but in conformity with prevailing
      nomenclature we regard it as a blastomyces. We shall term the disease which has
      been produced by this organism Blastomycetic Dermatitis. We give the name
      Blastomyces dermatitidis to the parasite which we have isolated and described in
      this paper. In closing we are of the opinion that it would be advisable to
      examine more carefully all tuberculous lesions of the skin, and especially those
      of tuberculosis verrucosa cutis, for the presence of blastomycetes. This can be
      readily and rapidly done by soaking the unstained sections in ordinary liquor
      potassse, when the organisms if present will stand out as doubly contoured
      refractive bodies.

PMID- 19866868
TI  - ON THE HAEMOCYTOZOA OF BIRDS.

PMID- 19866869
TI  - EXPERIMENTAL THYROIDISM.
AB  - FROM THE RESULTS OF THE VARIOUS EXPERIMENTS ALREADY DETAILED I FEEL JUSTIFIED IN
      DRAWING THE FOLLOWING CONCLUSIONS: (1) Absolutely fresh thyroid gland is not
      poisonous, in the usual sense of the term, when absorbed through the alimentary
      canal. (2) The symptoms of induced thyroidism are manifestations of an
      intoxication resulting from the ingestion of decomposed thyroid material, a
      conclusion that agrees in part with the previously related observations of Lanz.
      (3) The so-called experimental thyroidism is not specific for the thyroid only,
      for the ingestion of many substances derived from animal tissues other than the
      thyroid gland may produce an intoxication strikingly similar in every respect to
      that of experimental thyroidism. (4) Most, if not all, animal tissues yield
      substances which, if injected in large quantities directly into the circulation
      or beneath the skin, will produce an intoxication often very similar to that
      produced by injections of various substances derived from the fresh thyroid
      tissue. (5) The effects resulting from the intravascular or subcutaneous
      injections of aqueous extracts, decoctions and the concentrated extractives of
      the thyroid tissue, of the thymus, of muscle, etc., are by no means necessarily
      indicative of the function and the action of the hypothetical internal secretions
      of the same tissues during life. (6) The utilization of the fact that ingestion
      of decomposed thyroid material produces on certain occasions an intoxication with
      certain symptoms similar to some of those of G-raves' disease is not justifiable
      for the furtherance of the theory that the symptoms of exophthalmic goitre result
      from an over-production of the thyroid secretion. (7) Our results lead us to
      conclude with Drechsel that the fresh thyroid tissue yields at least probably two
      substances that are capable of palliating the symptoms of the acute cachexia in
      totally thyroidless dogs. (8) The thymus tissue also yields one and probably two
      substances that are as equally capable as the thyroid extractives of palliating
      the acute cachexia in totally thyroidless dogs. (9) Neither of the above
      substances is an enzyme, nor does either contain iodine. (10) Neither the feeding
      of minced raw thyroid glands, nor the injection of aqueous thyroid extracts,
      decoctions, and concentrated solutions of the extracted palliative thyroid
      principles is capable of keeping totally thyroidless young dogs alive longer than
      a few weeks (possibly three weeks). Still less capable are the thyroid
      preparations containing decomposition products. (11) The presence of one, or
      usually several, small accessory thyroid bodies, which gradually hypertrophy and
      wholly or partially assume the functions of the excised thyroid lobes, accounts
      for the occasionally long survival of thyroidectomized, thyroid-fed, young dogs.
      (12) Totally thyroidless young dogs are so quickly overwhelmed by the cachexia,
      and the intervals between the thyroidectomy and the onset of the severe dyspnoeic
      attacks and subsequent deaths differ so slightly, no matter which of the usual
      varieties of fresh food are employed, that kinds of fresh food cannot be
      unquestionably affirmed to influence the onset of the cachexia in any especially
      definite manner. Animal foods, in which constituents poisonous to rabbits have
      developed, probably slightly hasten the onset of the severer symptoms, and the
      vaunted remarkably modifying influence of a diet of ordinary milk, such as
      Breisacher observed, does not exist in the case of the totally thyroidless dog.
      (13) Monkeys whose general metabolism is disturbed in consequence of the removal
      of a greater portion of the thyroid gland, evidently become more susceptible to
      those constituents of meat that are poisonous to rabbits, and sufficient clinical
      evidence exists for concluding that probably a like susceptibility to animal
      foods containing such constituents also exists in men when the function of the
      thyroid gland is sufficiently disturbed. (14) And, finally, as regards the
      thyroid factor in the pathology of exophthalmic goitre, I agree with Gley that
      the majority of the symptoms in many patients with that disease can apparently,
      from an experimental standpoint, be as plausibly explained by the hypothesis of
      partially deficient thyroid activity as by the hypothesis of augmentation of
      thyroid function.

PMID- 19866871
TI  - A TERATOMA OF THE ABDOMINAL CAVITY.

PMID- 19866870
TI  - THE PHYSIOLOGICAL EFFECTS OF EXTRACTS OF THE HYPOPHYSIS CEREBRI AND INFUNDIBULAR
      BODY.

PMID- 19866872
TI  - NOTE ON DR. D. W. MONTGOMERY'S CASE OF TERATOMA.

PMID- 19866873
TI  - AN EXPERIMENTAL STUDY OF FAT STARVATION WITH ESPECIAL REFERENCE TO THE PRODUCTION
      OF SEROUS ATROPHY OF FAT.
AB  - THE FOLLOWING INFERENCES MAY BE MADE FROM THE FOREGOING STUDY: 1. The lesions
      resulting from fat starvation, at least in the case of pigs, do not resemble or
      even suggest those of rickets. 2. Prolonged fat starvation leads to the entire
      disappearance of fat from the adipose tissues. The form of fat atrophy observed
      as the result of experimental fat starvation corresponds to the serous fat
      atrophy described by Flemming, and is essentially the same type of fat atrophy as
      that found in the epicardial and perirenal fat in the human subject as the result
      of wasting disease. 3. The. lecithins of the brain and the fat of the liver are
      not materially reduced by fat starvation. 4. Fat starvation does not lead to
      advanced serous fat atrophy of the subcutaneous fat if the animal be given a
      large excess of carbohydrate food or a considerable excess of the carbohydrate
      and proteid constituents of milk. 5. Fat starvation causes a very imperfect
      absorption of the salts of P(2)O(5) from the intestine.

PMID- 19866874
TI  - STUDIES ON TRICHINOSIS, WITH ESPECIAL REFERENCE TO THE INCREASE OF THE
      EOSINOPHILIC CELLS IN THE BLOOD AND MUSCLE, THE ORIGIN OF THESE CELLS AND THEIR
      DIAGNOSTIC IMPORTANCE.
AB  - TO SUMMARIZE, WE HAVE BEEN ABLE TO DEMONSTRATE: (1) In a case of acute
      trichinosis an extensive leucocytosis, with great absolute and relative increase
      in the number of eosinophilic cells in the blood, associated with a coincident
      decrease in the quantity of neutrophilic elements. (2) From the examination of
      specimens of muscle removed during life, besides the peculiar degenerations of
      the muscle, a longitudinal splitting of some of the fibres; a remarkable
      transverse splitting of others; a great proliferation of nuclei, about many of
      which vacuoles are seen; and large numbers of polymorphonuclear eosinophilic
      cells, which are especially prevalent in the more degenerated areas. (3) In a
      second case (after death), besides similar changes in the muscle, large numbers
      of eosinophiles throughout the infested portion. (4) In two other cases, during
      life, a great increase of the eosinophilic cells in the blood, with a coincident
      decrease of the polymorphonuclear neutrophiles, associated with leucocytosis,
      though of less extent than in the first case. (5) In pieces of muscle removed in
      these last two cases changes in most respects similar to those cited in the first
      case, but of less degree. (6) The similar character of the nuclei of the
      eosinophiles and the neutrophiles both in the blood and in the muscle, and the
      presence in the first case of certain cells which might be regarded as forms
      transitional between neutrophiles and eosinophiles, suggesting the possibility
      that the increase in the latter elements may, in these instances, take place in
      the muscles by direct transition from the neutrophiles.

PMID- 19866875
TI  - ON THE PRESENCE OF THE TYPHOID BACILLUS IN THE URINE.
AB  - (1) Typhoid bacilli were demonstrated in the urines of 9 out of 38 typhoid
      patients (about 25 per cent). 172 specimens were examined with 44 positive
      results. (2) The bacilli, when demonstrated, were always present in large numbers
      and in practically pure culture. (3) The bacilli appeared first in the later
      stages of the disease and persisted in the great majority of cases far into
      convalescence. The urines of typhoid patients should, therefore, not only be
      rigidly disinfected during the disease, but they should also be carefully
      supervised during convalescence. (4) The typhoid bacilli were practically always
      associated with albuminuria and the presence of renal casts. On the other hand
      urines containing considerable amounts of albumin and casts in large numbers
      often showed no typhoid bacilli. (5) Irrigation of the bladder with antiseptic
      solutions offers a possible means for removing permanently the bacilli from the
      urine.

PMID- 19866876
TI  - THE BRANCHED FORM OF THE BACILLUS TUBERCULOSIS IN SPUTUM.

PMID- 19866877
TI  - THE EFFECTS UPON THE BLOOD OF THE TUFNELL METHOD AND THE CALCIUM SALTS IN THE
      TREATMENT OF AORTIC ANEURISM.

PMID- 19866878
TI  - EXPERIMENTS ON THE APPLICATION OF THE ROENTGEN RAYS TO THE STUDY OF ANATOMY.

PMID- 19866879
TI  - ON A FORM OF DEGENERATION OF STRIATED MUSCLE MET WITH IN THE UVULA.

PMID- 19866880
TI  - THE FATE OF THE GIANT CELLS WHICH FORM IN THE ABSORPTION OF COAGULATED BLOOD
      SERUM IN THE ANTERIOR CHAMBER OF THE RABBIT'S EYE.
AB  - The conclusion seems warranted that the giant cells formed in the absorption of
      coagulated blood serum inserted into the anterior chamber of the rabbit's eye
      subdivide again into uninuclear small cells that take part with other new-formed
      cells derived from the lining of this space to form a densely fibrillated mass of
      tissue that resembles quite closely the cornea in its structure. This
      demonstration materially strengthens the opinion expressed by the writer in his
      previous article in this Journal,* that the giant cells in healing non
      degenerated tuberculous tissue may separate into small living cells, and that the
      giant cells of tuberculosis are not necrobiotic elements from the very moment and
      from the very mode of their formation, as has been the general teaching,
      especially in Germany.

PMID- 19866881
TI  - REGENERATION OF NERVE FIBRES IN THE CENTRAL NERVOUS SYSTEM.

PMID- 19866882
TI  - EXPERIMENTAL FAT NECROSIS: THE ACTION OF PANCREATIC TISSUE UPON SUBCUTANEOUS
      ADIPOSE TISSUE.

PMID- 19866883
TI  - A CONTRIBUTION TO THE STUDY OF THE PATHOGENESIS OF THE BACILLUS PYOCYANEUS, WITH
      SPECIAL REFERENCE TO ITS RELATION TO AN EPIDEMIC OF DYSENTERY.

PMID- 19866884
TI  - A HISTOLOGICAL STUDY OF TYPHOID FEVER.
AB  - The typhoid bacillus produces a mild diffusible toxine, partly within the
      intestinal tract, partly within the blood and organs of the body. This toxine
      produces proliferation of endothelial cells which acquire for a certain length of
      time malignant properties. The new-formed cells are epithelioid in character,
      have irregular, lightly staining, eccentrically situated nuclei, abundant,
      sharply defined, acidophilic protoplasm, and are characterized by marked
      phagocytic properties. These phagocytic cells are produced most abundantly along
      the line of absorption from the intestinal tract, both in the lymphatic apparatus
      and in the blood-vessels. They are also produced by distribution of the toxine
      through the general circulation, in greatest numbers where the circulation is
      slowest. Finally, they are produced all over the body in the lymphatic spaces and
      vessels by absorption of the toxine eliminated from the blood-vessels. The
      swelling of the intestinal lymphoid tissue of the mesenteric lymph nodes, and of
      the spleen is due almost entirely to the formation of phagocytic cells. The
      necrosis of the intestinal lymphoid tissue is accidental in nature and is caused
      through occlusion of the veins and capillaries by fibrinous thrombi, which owe
      their origin to degeneration of phagocytic cells beneath the lining endothelium
      of the vessels. Two varieties of focal lesions occur in the liver: one consists
      of the formation of phagocytic cells in the lymph spaces and vessels around the
      portal vessels under the action of the toxine absorbed by the lymphatics; the
      other is due to obstruction of liver capillaries by phagocytic cells derived in
      small part from the lining endothelium of the liver capillaries, but chiefly by
      embolism through the portal circulation of cells originating from the endothelium
      of the blood-vessels of the intestine and spleen. The liver cells lying between
      the occluded capillaries undergo necrosis and disappear. Later the foci of cells
      degenerate and fibrin forms between them. Invasion with polymorphonuclear
      leucocytes is rare. Many of the phagocytic cells pass through the liver and
      lungs, and get into the general circulation. A few come from the abdominal
      lymphatics through the thoracic duct.

PMID- 19866885
TI  - THE LEUCOCYTOSIS OF LABOR AND THE PUERPERIUM.

PMID- 19866886
TI  - ONE OF THE CONDITIONS UNDER WHICH DISCONTINUOUS STERILIZATION MAY BE INEFFECTIVE.

PMID- 19866887
TI  - NOTES UPON AN EPIDEMIC OF FOWL CHOLERA AND UPON THE COMPARATIVE PRODUCTION OF
      ACID BY ALLIED BACTERIA.
AB  - (a). The bacillus isolated by me from the outbreak of choleraic diarrhoea
      corresponds closely in all essential particulars with that of European chicken
      cholera. (b). It differs, consequently, from that isolated from previous
      outbreaks of choleraic diarrhoea in the United States. (c). A study of the acid
      production by this and allied bacilli would seem to show that the amount of acid
      produced by so variable a microbe varies greatly and is incapable of affording a
      further means of distinguishing between allied forms.

PMID- 19866888
TI  - DIFFUSE SARCOMA OF THE CEREBRAL AND SPINAL PIA MATER.

PMID- 19866889
TI  - ACUTE INTERSTITIAL NEPHRITIS.
AB  - Acute interstitial nephritis is found in the infectious diseases of children,
      particularly in diphtheria and scarlet fever, but may be met with in other
      infectious diseases. The disease is characterized by general and focal
      infiltration of the interstitial tissue of the kidney with cells which correspond
      to those which Unna has described under the name of plasma cells. The focal
      character of the infiltration is marked; even in the cases in which all parts of
      the kidney show some interstitial cellular infiltration the cells are most
      abundant in certain foci. These foci are found in three places: in the boundary
      zone of the pyramids, in the sub-capsular region of the cortex, and around the
      glomeruli. A considerable number of cases is found in which the blood-vessels of
      the boundary zone of the pyramids contain nnmbers of lymphoid and plasma cells
      without any infiltration of the interstitial tissue. The new cells in the
      interstitial tissue are due to emigration from the blood-vessels and
      multiplication by mitotic division of the cells which have emigrated. The cells
      can emigrate as plasma. cells or as lymphoid cells, and the latter may change
      into plasma cells in the tissues. In the normal individual, plasma cells may be
      formed in the mucous membrane of the intestine, where they practically form the
      entire tissue between the epithelium and the muscularis mucosa, and to a limited
      extent in the spleen. In diphtheria, in scarlet fever, and probably in a number
      of infectious diseases, plasma cells are formed in great numbers in the spleen
      and bone-marrow, and to some extent in the lymphatic glands. In the spleen they
      are formed from the cells of the Malpighian bodies, which are often principally
      composed of them, and to some extent from the cells in the pulp. They are formed
      from the lymphoid cells. No adequate explanation is found for the focal character
      of the lesions in the kidneys. There is some ground for believing that the
      physical conditions of the circulation may have something to do with their
      accumulation in the vessels in certain places. It is also possible that in the
      interstitial foci there may be soluble substances which exert a positive
      chemotaxis for them. Such substances may be foundin the urine, which may exert
      its influence on the interstitial tissue in different places. The explanation of
      the foci cannot be found in primary focal degeneration of the epithelium.
      Epithclial degeneration in these cases is always present, but it is diffuse. In
      foci where it is more intense and due to the interstitial changes, polynuclear
      leucocytes are found in the tissue, in the degenerated epithellum and in the
      tubules. Folynuclear lencocytes and not plasma cells are attracted by degenerated
      tissue. The foci are not due in these cases to the local action of bacteria. In a
      number of the cases in which interstitial nephritis was found the kidneys were
      shown to be sterile both by cultures and by microscopical examination. In cases
      where bacteria were present they were found only in small numbers in cultures and
      not on microscopical examination, and their connection with the foci could not be
      demonstrated. In three cases plasma cells were found in the interstitial tissue
      in definite bacterial diseases of the kidney. In these cases they were not found
      in connection with the lesions produced directly by the bacteria, but in the
      periphery of the purulent foci.

PMID- 19866890
TI  - A CASE OF MYCETOMA (MADURA FOOT).

PMID- 19866891
TI  - PSEUDO-TUBERCULOSIS HOMINIS STREPTOTHRICHA.

PMID- 19866892
TI  - A COMPARATIVE STUDY OF BOVINE TUBERCLE BACILLI AND OF HUMAN BACILLI FROM SPUTUM.

PMID- 19866893
TI  - THE RELATION OF THE TOXICITY OF DIPHTHERIA TOXIN TO ITS NEUTRALIZING VALUE UPON
      ANTITOXIN AT DIFFERENT STAGES IN THE GROWTH OF CULTURE.
AB  - Until recently diphtheria " toxin " was supposed to be a single definite
      substance and to have a definite toxicity in animals and neutralizing power for
      antitoxin. A fatal dose of toxin, without regard to the conditions under which it
      was produced or preserved, was supposed to require always the same quantity of
      antitoxin to neutralize it. Ehrlich's researches have completely done away with
      this theory, and have substituted for it one which assumes the toxin to be only
      at its origin a single definite chemical compound with definite physiological and
      antitoxic properties. According to Ehrlich the toxin is an unstable substance
      which readily loses its toxicity, while at the same time its affinity for
      antitoxin may be either increased or decreased. Its neutralization by antitoxin
      he considers to be due to a chemical union between the toxin and the antitoxin.
      The results of our experiments as detailed in this paper are fully in accord with
      those published by Ehrlich, as to the varying neutralizing value of a minimal
      fatal dose of " toxin "; they, however, go further and indicate roughly a general
      law in accordance with which these changes occur. The neutralizing value of a
      fatal dose of toxin is at its lowest in the culture fluid when the first
      considerable amounts of toxin have been produced. After a short period, during
      which the quantity of toxin in the fluid is increasing, the neutralizing value of
      the fatal dose begins to increase, at first rapidly, then more slowly. While the
      culture is still in vigorous growth and new toxin is being produced, the
      neutralizing value of the fatal dose fluctuates somewhat, but with a generally
      upward tendency. After the cessation of toxin production the neutralizing value
      of the fatal dose increases steadily until it becomes five to ten times its
      original amount. In our experiments the greatest value for L(+) was 126, the
      least 27. As at 6 hours L(+) was only 72 and at 28 hours only 91, we doubt
      whether L(+) ever reaches above 150, and therefore hardly expect Ehrlich's
      figures of 200 to be realized. When we seek to analyze the above-described
      process, we find certain facts which seem partly to explain it. Experiments have
      shown that filtered toxin, preserved for any length of time in conditions under
      which access of air occurs, gradually loses in both its toxicity and neutralizing
      power, and that it loses more rapidly in the former property than in the later.
      Thus, while the fatal dose of a toxin preserved for one year rose from .01 cc. to
      .55 cc., it lost only half as much in neutralizing value, one unit neutralizing
      at first 1 cc., at the end of the year 25 cc. These processes take place more
      rapidly at room temperature than in the ice chest, and in the incubator than in
      the room. In the fluid holding the living bacilli we have, therefore, after the
      first few hours of toxin formation, a double process going on, one of
      deterioration in the toxin already accumulated, which tends to increase the
      neutralizing value of the fatal dose, the other of new toxin formation, which
      probably tends to diminish the neutralizing value. The chemical changes produced
      by the growth of the bacilli in the bouillon tend to aid one or the other of
      these processes and so to make from hour to hour slight changes in the value of
      the fatal dose. Later, with the period of cessation of toxin production, the
      gradual deterioration of the toxicity alone continues, and the fatal dose
      gradually and steadily increases in its neutralizing value. Ehrlich's theories,
      as to the splitting up of " toxin " into toxoids having little or no toxicity but
      on the average full neutralizing power for antitoxin, have not in our opinion
      been substantiated by the results of these experiments. The difference between
      the amount of toxin mixed with a unit of antitoxin which causes the first
      symptoms and that causing death upon the fourth day would be, it is true,
      explained by his theory, but the failure of this difference to be greater where,
      by his theories, epitoxoids should be in great abundance prevents our acceptance
      of his views. The fact of the greater neutralization value of a fatal dose of a
      deteriorated toxin would be accounted for on his protoxoid theory. This, however,
      is not proof of its correctness, as other theories, such as the production by the
      diphtheria bacillus of two or more closely allied toxins, similar to the allied
      alkaloids produced by plants, would equally account for it, if we supposed the
      one which had the greater neutralization value was more resistant to destruction
      than the other. We only advance this theory to call attention to the fact that
      many theories can on paper explain a process without necessarily being thereby
      established. Even if his theories prove partially correct, we feel certain that
      his formula for standardizing toxins is founded upon error and cannot be employed
      for the purpose intended by him. While we do not believe, therefore, that he has
      changed the principles of testing antitoxin, yet we believe he has contributed
      greatly to uniformity in results by calling attention to the necessity of
      selecting a suitable toxin and by employing and distributing an antitoxin as a
      standard to test toxins by. In this way smaller testing stations can make their
      results correspond with those of the central station. In spite of the great
      variations in the neutralizing value of a fatal dose in different toxins, we do
      not believe there has been any such great difference in the toxins used by the
      different stations for testing purposes. Most laboratories have taken the culture
      fluid at about the time of its greatest toxicity, and the neutralizing value of a
      fatal dose of this toxin would seldom vary more than 10 per cent above or below
      the standard now adopted in Germany by the government testing station, this
      latter being presumably as close as possible to that used to establish the
      original Behring-EhrIich unit. Where error has been made, it has usually been by
      taking too old culture fluids, which would cause the antitoxin strength of
      samples tested to be estimated below and not above its real value. Culture 8,
      which is used not only by us but by many other laboratories in the United States
      and Europe, fortunately produces on the 6th day, the time at which the culture is
      usually removed, a toxin which grades Elirlich's antitoxin within five per cent
      of the strength given by him. We believe that by using such a bacillus, we can,
      after gaining a fuller knowledge of its characteristics, obtain a toxin of a
      known and suitable neutralizing value, and thus always correctly standardize an
      antitoxic serum. Meanwhile a fairly permanent antitoxin, such as Ehrlich
      provides, is of immense value in insuring a uniform though not necessarily
      correct standard among the different testing stations and in allowing of
      comparison between them.

PMID- 19866894
TI  - AN EXPERIMENTAL STUDY OF THE DIRECT INOCULATION OF BACTERIA INTO THE SPLEEN OF
      LIVING ANIMALS; AND A CONTRIBUTION TO THE KNOWLEDGE OF THE IMPORTANCE OF A LESION
      IN ANIMAL TISSUE FOR THE LODGMENT AND MULTIPLICATION OF BACTERIA WITHIN IT.
AB  - I. Cultures of B. coli communis, B. typhosus and Staph. pyogenes aureus, when
      injected into the tissue of the normal spleen, soon disappear from that organ,
      and indeed from the normal body generally. II. Bacteria injected into a spleen
      after the whole or a part of the vessels have been tied, multiply in the spleen
      with great rapidity and continue to supply bacteria to the blood, whence in the
      healthy body they soon disappear. III. Bacteria injected into the spleen, or
      subcutaneous tissue, or into the blood current through the ear vein, in cases in
      which moderate lesions have been made by cauterization or compression in the
      spleen, liver, kidney, uterus, testicle, peritoneum, or subcutaneous tissue,
      usually find lodgment in these lesions and multiply there. IV. Even in cases in
      which numerous foci existed, from which the blood was constantly provided with a
      fresh supply of bacteria, only few bacteria were found at any time in the blood.

PMID- 19866895
TI  - ON THE PRESENCE OF CHOLIN AND NEURIN IN THE INTESTINAL CANAL DURING ITS COMPLETE
      OBSTRUCTION : A RESEARCH ON AUTOINTOXICATION.
AB  - My experiments lead me to believe that complete occlusion of the small intestine
      at its lower end will give rise to the occurrence of cholin, neurin and perhaps
      other bases, provided the food taken contains any considerable quantity of
      lecithin. It is not improbable that still other poisons are formed by bacterial
      action from other constituents of the food in cases of intestinal obstruction.
      While cholin would have to be absorbed in relatively large amounts to exert a
      marked toxic action in human beings it is otherwise with neurin, which is many
      times more intense in its action and must be classed with the exceedingly active
      poisons. It has been shown both by the experiments of Schmidt and Weiss and also
      by those recorded in this paper that the poisonous neurin may be formed from
      cholin by bacteria. In its physiological action neurin agrees closely with
      muscarin; especially to be noted here is the paralytic action on the heart and
      its power to increase the intestinal movements to such an extent that continual
      evacuations occur. Whether the ptomaine which was found by me is poisonous 1
      cannot yet say. It must be considered proved, however, that highly toxic
      substances may arise in the intestinal canal during its complete occlusion. The
      method of treating cases of intestinal obstruction, before surgical means are
      resorted to, namely, washing out the stomach and as much of the gut as possible
      often reduces the violent paristalsis and this is due, perhaps, to the removal of
      substances out of which irritating and toxic products are formed by bacteria. In
      conclusion, I would remark that our knowledge of the fate of lecithin in the
      digestive canal under normal conditions is very deficient. The assumption that it
      is saponified by the fat-splitting enzyme of the pancreatic juice, thus yielding
      cholin, glycero-phosphoric acid and fatty acids, rests on the work of Bokai in
      1877 and, as that investigator himself admits, without excluding bacterial
      action. This omission throws grave doubts on the results. If the assumption of
      Bokai be correct, caution must be observed in the use of some foods that have
      been considered most nutritious and healthful; for instance, the ingestion of a
      meal made up largely of eggs would hardly be without danger because of the
      poisonous action of the large quantity of cholin liberated from the lecithin and
      the probability of the formation of the highly poisonous neurin. It is my purpose
      in the near future to examine this question with the help of modern methods.

PMID- 19866896
TI  - ON ALTERATIONS IN THE COMPOSITION OF THE BLOOD RESULTING FROM EXPERIMENTAL DOUBLE
      NEPHRECTOMY.

PMID- 19866897
TI  - ON THE INFLUENCE OF FASTING UPON THE BACTERICIDAL ACTION OF THE BLOOD.

PMID- 19866898
TI  - GLYCOSURIA IN DIPHTHERIA.
AB  - (1) There is a transitory glycosuria in diphtheria, which is found frequently in
      the severe cases and is usually present in the fatal ones. (2) This glycosuria is
      often associated with albuminuria. (3) Injections of diphtheria antitoxin are
      occasionally followed for a few days by a slight glycosuria.

PMID- 19866899
TI  - ON THE VALUE OF UROTROPIN AS A URINARY ANTISEPTIC WITH ESPECIAL REFERENCE TO ITS
      USE IN TYPHOID FEVER.

PMID- 19866900
TI  - REGENERATION OF THE DORSAL ROOT FIBRES OF THE SECOND CERVICAL NERVE WITHIN THE
      SPINAL CORD.

PMID- 19866901
TI  - ACTION OF FORMALDEHYDE ON ENZYMES AND ON CERTAIN PBOTEIDS.
AB  - THE FOLLOWING GENERAL CONCLUSIONS MAY BE DRAWN FROM THE PRECEDING WORK: Fibrin is
      altered by formaldehyde and is then less easily digested by pepsin and by
      trypsin. Papain is apparently unable to digest fibrin even when this is exposed
      to very weak formaldehyde (1:1000) for a very short time. The casein of milk, on
      contact with formaldehyde, undergoes rapid alteration and is as a result not
      coagulated by rennet, or but very slowly. Such altered casein, like similar
      fibrin, is not readily digested by the proteolytic ferments. The longer the
      formaldehyde acts on casein and on fibrin the more marked is the result. Pepsin
      is not affected by a one per cent solution of formaldehyde, even when the mixture
      has stood for four weeks. Even a five per cent solution of formaldehyde acting
      for three weeks has no effect on pepsin. Contrary results obtained by others are
      due to an alteration of the fibrin by the formaldehyde. A putrid solution of
      pepsin in distilled water one month old digests fibrin as readily as a fresh
      solution. Rennet is not affected even by a four per cent solution of formaldehyde
      acting for several weeks. The absence of coagulation at times is due to the
      action of formaldehyde on the casein of the milk and not on the rennet ferment.
      Papain is very quickly altered by formaldehyde, even in very dilute solution.
      Moreover, it is unable to digest fibrin that has been exposed to the action of a
      very dilute solution of formaldehyde for a short time. Trypsin is altered by
      formaldehyde to such an extent that digestion of fibrin will not take place, or
      but very slowly. The extent to which trypsin is affected by formaldehyde depends
      largely upon the amount of organic matter present, as well as on the amount of
      ferment in the solution. Amylopsin is not destroyed by very dilute solutions of
      formaldehyde, but stronger solutions decrease the activity of the ferment, and if
      used in sufficient concentration will destroy it completely. Ptyalin, like the
      diastatic ferment of the pancreas, is not destroyed by dilute solutions of
      formaldehyde. If the latter is used in rather strong concentration and allowed to
      act for some time it will destroy the ferment. The action of formaldehyde is more
      rapid and more marked at a slightly elevated temperature than at ordinary room
      temperature. Malt diastase, unlike the diastatic ferments of the saliva and
      pancreatic solution, is not destroyed by formaldehyde when this is used in
      moderate amount and at ordinary temperature. Unlike pepsin, a solution of malt
      diastase readily undergoes decomposition on standing even for one or more days.
      This destruction is undoubtedly due to bacteria since it does not take place when
      formaldehyde is present. Consequently the favoring action which formaldehyde
      apparently exerts on diastase really consists in the inhibition of the growth of
      micro-organisms, and hence the diastase is protected against decomposition.

PMID- 19866902
TI  - A SECOND CASE OF GONORRHOEAL SEPTICAEMIA AND ULCERATIVE ENDOCARDITIS WITH
      OBSERVATIONS UPON THE CARDIAC COMPLICATIONS OF GONORRHOEA.
AB  - (1) An acute gonorrhoeal urethritis may be the starting point for a grave general
      septicaemia with all its possible complications. (2) These infections may be
      mixed or secondary, due to the entrance into the circulation of organisms other
      than the gonococcus, or they may be purely gonococcal in nature. (3) Endocarditis
      is an occasional complication of gonorrhoea. (4) This endocarditis may be
      transient, disappearing with but few apparent results, or it may leave the
      patient with a chronic valvular lesion, or it may pursue a rapidly fatal course
      with the symptoms of acute ulcerative endocarditis. (5) The endocarditis
      associated with gonorrhoea is commonly due to the direct action of the
      gonococcus, hut may be the result of a secondary or mixed infection. (6)
      Pericarditis may also occur as a complication of gonorrhoea, but it is less
      frequent than endocarditis. It may, as in the case of the latter, be the result
      either of a pure gonococcal or of a mixed infection. (7) Grave myocardial
      changes, necroses, purulent infiltration, embolic abscesses are common in the
      severe gonococcal septicaemias. (8) In instances of gonococcal septicaemia the
      diagnosis may, in some cases, be made during life by cultures taken from the
      circulating blood according to proper methods.

PMID- 19866903
TI  - HAEMORRHAGIC SEPTICAEMIA IN MAN DUE TO CAPSULATED BACILLI.

PMID- 19866904
TI  - BACILLUS CAPSULATUS (BACILLUS PNEUMONIAE OF FRIEDLAENDER?) WITH ESPECIAL
      REFERENCE TO ITS CONNECTION WITH ACUTE LOBAR PNEUMONIA : A REPORT OF TWELVE CASES
      IN WHICH BACILLUS CAPSULATUS OCCURRED IN THE MEDICAL AND SURGICAL WARDS OF THE
      BOSTON CITY HOSPITAL.

PMID- 19866905
TI  - REPORT OF EXPERIMENTAL WORK ON THE DILUTION METHOD OF IMMUNIZATION FROM RABIES.
AB  - 1. I have simplified the dilution method by using a stock glycerine emulsion of
      the virulent cord, from which the desired dilutions can be readily prepared. The
      proportion of glycerine should not exceed (1/5) part, if it is desired to retain
      the full virulence of the emulsion. 2. There is some danger of giving rabies to
      animals in the dilution immunization treatment, a danger which is not present in
      the Pasteur method. 3. The dried-cord method does not rest solely upon the
      principle of dilution, but is based also upon attenuation of the virus. 4. The
      Pasteur method being entirely free from the element of danger which pertains to
      the glycerine dilution method and resting upon a sounder experimental basis is
      the one to be preferred.

PMID- 19866906
TI  - A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL
      INFECTION WITH THE TYPHOID BACILLUS.
AB  - (1) The application of the Nissl method to the study of the motor cells of the
      spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever,
      shows that these cells regularly suffer pathological changes in the course of the
      infection. (2) The alterations in the motor cells are more constant and of a
      severer grade than are those in the cells of the sensory ganglia. The more
      characteristic changes consist of disintegration, solution and destruction of the
      chromatic substance of the cell starting from the axone hillock and proceeding
      toward the nucleus. Coincidently the nuclei of the affected cells seek the
      periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While
      this central form of ehromatolysis is the prevailing type of pathological change,
      disintegration, etc., of the Nissl bodies situated in the periphery of the cell
      and in the dendrites is also observed (peripheral chromatolysis). (4) In
      experimental infection with typhoid bacilli in rabbits a similar series of
      lesions in the corresponding nerve cells in the spinal cord and ganglia is
      encountered. (5) The main or central type of lesions discovered is identical with
      that found in man and animals after section, destruction, or even slight injury
      of the peripheral nerves. (6) The examination of the peripheral nerves arising
      from the lumbar segment of the cord (the site in man and rabbit of the most
      profound changes) in rabbits inoculated with typhoid bacilli showed well-marked
      evidences of parenchymatous degeneration. (7> It is probable that lesions of the
      peripheral nerves in typhoid fever in human beings are common and that the post
      typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of
      the chromatic granules may take place in the affected nerve cells, the new
      formation beginning about the nucleus and extending through the protoplasm.

PMID- 19866907
TI  - THE THERMAL DEATH-POINT OF TUBERCLE BACILLI IN MILK AND SOME OTHER FLUIDS.
AB  - 1. Tubercle bacilli when suspended in. distilled water, normal salt solution,
      bouillon and milk, are destroyed at 60 degrees C. in 15 to 20 minutes. The larger
      number are destroyed in 5 to 10 minutes. 2. When tubercle bacilli are suspended
      in milk, the pellicle which forms during the exposure at 60 degrees C. may
      contain living bacilli after 60 minutes.

PMID- 19866908
TI  - THE CHARGES PRODUCED BY THE GROWTH OF BACTERIA IN THE MOLECULAR CONCENTRATION AND
      ELECTRICAL CONDUCTIVITY OF CULTURE MEDIA.

PMID- 19866909
TI  - ON SUPRA-ARTERIAL EPICARDIAL FIBROID NODULES.

PMID- 19866910
TI  - THE ORGANISM IN A CASE OF BLASTOMYCETIC DERMATITIS.

PMID- 19866911
TI  - A CASE OF HAEMOCHROMATOSIS.-THE RELATION OF HAEMOCHROMATOSIS TO BRONZED DIABETES.
AB  - (1) There exists a distinct morbid entity, haemochromatosis, characterized by the
      widespread deposition of an iron-containing pigment in certain cells and an
      associated formation of iron-free pigments in a variety of localities in which
      pigment is found in moderate amount under physiological conditions. (2) With the
      pigment accumulation there is degeneration and death of the containing cells and
      consequent interstitial inflammation, notably of the liver and pancreas, which
      become the seat of inflammatory changes accompanied by hypertrophy of the organ.
      (3) When chronic interstitial pancreatitis has reached a certain grade of
      intensity diabetes ensues and is the terminal event in the disease.

PMID- 19866912
TI  - THE ACTION OF HEPATIC, RENAL AND OTHER CELLS ON PHENOL AND INDOL, UNDER NORMAL
      AND PATHOLOGICAL CONDITIONS.

PMID- 19866913
TI  - ON THE INTERPRETATION OF PULSE-TRACINGS.

PMID- 19866914
TI  - ON THE DIPLOCOCCOID FORM OF THE COLON BACILLUS.

PMID- 19866915
TI  - THE RELATION OF DEXTROSE TO THE PRODUCTION OF TOXIN IN BOUILLON CULTURES OF THE
      DIPHTHERIA BACILLUS.
AB  - 1. Dextrose is not in itself injurious but rather favorable to toxin production.
      When added in quantities not exceeding 0.2 per cent to peptone bouillon freed
      from fermentable acid-producing substances (muscle sugar) it leads to a maximum
      accumulation of toxin by utilizing the available peptone to the best advantage.
      2. The different courses taken by cultures of diphtheria bacilli in ordinary
      unfermented peptone bouillon containing muscle sugar and in peptone bouillon made
      from fermented infusion to which 0.1 to 0.2 per cent dextrose has been added are
      manifested by an increased production of toxin in the latter as well as by a
      rapid return from an acid to an alkaline reaction. In the former an acid reaction
      may prevail even under most favorable conditions. 3. These differences may be
      explained by assuming either that the acid products of the muscle sugar are
      different from those of dextrose and non-utilizable, or else that the bouillon
      contains certain other unknown inhibitory substances removed during fermentation.
      The use of synthesized media and an analysis of the acid products in fermented
      bouillon plus dextrose and in unfermented bouillon would aid in explaining the
      differences. 4. Among the accessory conditions which favor the toxin production
      in unfermented bouillon, as pointed out by Park and Williams, are increased
      quantities of peptone, well developed surface growth of the diphtheria bacilli,
      and a low initial acid reaction (phenolphthalein). In fermented bouillon these
      accessory conditions are also favoring, though of legs importance.

PMID- 19866916
TI  - THE ORIGIN OF FAT FROM PROTEIN IN THE SO-CALLED FATTY METAMORPHOSIS OF PHOSPHORUS
      POISONING.
AB  - 588.780 grm. of frogs, all of the same sex, of the same comparative approximate
      weights, taken from the ground about the same time, kept awake and without food
      for nearly the same time, were divided into equal groups; the one group was
      poisoned with phosphorus, the other group held as a control. The frogs in the
      poisoned group lost in dried residue 8.821 grm. or 16.5 per cent of the dried
      residue of the control group; 1.182 grm. of nitrogen, corresponding to 7.388 of
      proteid, or 18.45 per cent of the nitrogen and protein in the control frogs;
      1.026 grm. of fat, or 22.64 per cent of the fat in the control animals; and 0.261
      grm. glycogen, or 13.3 + per cent of the glycogen in the control frogs. I believe
      that it is obvious that in these experiments no fats were produced from protein.
      Mathematically, it is possible to conceive that fats could have been formed but
      entirely burned up. As previously stated, the carbon in the proteid lost during
      the poisoning was equivalent to 4.600 grm. of fat, and it is conceivable that
      these 4.600 grm. of fat were formed, but that they, together with the 1.026 grm.
      of fat actually lost during the experiments, were burned. In brief, the fat
      combustion might have been tremendously increased, and masked an actual fat
      formation. This however is unsupported by evidence, and is highly improbable. It
      is hard to conceive that in an organism whose katabolic functions were greatly
      augmented as the result of phosphorus poisoning, in which protein, fat, and
      glycogen were being burned in excess, the carbon of the protein would first have
      been converted into fat and then the fat burned as such. I believe the only
      conclusion which can be drawn from these experiments is that no fat was formed as
      the result of phosphorus poisoning. Thus the fatty degenerations so-called which
      occurred in these frogs did not comprehend any formation of fat at all, but
      simply the deposition of fat. These results are directly opposite to those of
      Polimanti. Polimanti apparently did not weigh his animals before the beginning of
      the experiment, and based his calculations upon the relation of the fat to the
      dried residue. Obviously his calculation was based upon the assumption that the
      dried residue of a frog was unaffected by phosphorus poisoning. Polimanti, in
      declining to base his calculations upon the weight of the animals when dead,
      states that as water is often increased, such a calculation would be misleading.
      But since the dried residue may and does vary, calculations based upon it are
      also misleading, and thus the only proper basis of calculation is the original
      weight of the frogs before the experimentation. Calculated upon the basis of the
      dried residue, in my material the percentage of fat in the control animals was
      8.48 per cent, in the poisoned animals 7.86 per cent, so that, even upon the
      basis of Polimanti's incorrect calculation, in my experiments fat was lost in
      notable quantity. Just before this study was completed, the publication of
      Athanasiu, (8) from Pflueger's laboratory, appeared. Operating with a large
      number of frogs, and under varying conditions, with careful methods and rigid
      controls, Athanasiu reached the conclusions: that phosphorus poisoning has no
      effect upon the total quantity of fat in frogs; that it has little effect upon
      the nitrogen; that it produces a diminution in the quantity of glycogen; and that
      the fatty degenerations are really fatty infiltrations. While my results agree
      with those of Athanasiu in the essential point, that no fat was produced by
      phosphorus poisoning, they differ in that the poisoned frogs, in my experiments,
      lost fat and protein as well as glycogen, while his frogs lost only glycogen.
      Since our methods were almost the same, the differences must have resided either
      in the conditions surrounding the experiments, or in the animals. I do not
      believe that such differences exist between the Rana fusca and esculenta of
      Europe and the Rana palustris of America as to explain the differences in our
      results. These differences I believe may be explained by varying conditions. My
      animals were kept in a warm cellar, at a temperature of from 18 to 20 degrees C.
      The period of poisoning with Athanasiu's frogs varied from one to six days; all
      of my frogs lived over six days, most of them ten or twelve days. Since we know
      that the katabolic actions of most poisons are greater in prolonged
      intoxications, it is fair to assume that the time element was the factor in the
      production of my results. While it would be unscientific and illogical to state
      that fat cannot be formed from protein, the fact stands that it has never been
      shown, either in physiology or pathology, that fats are formed from protein. On
      the contrary, nearly all of the careful work upon the question has yielded
      negative results. Not. only has it never been shown that, in fatty degeneration
      so-called, fat is formed from the cellular protein, but it has never been
      demonstrated that fat is then formed at all, even from glucosides, etc.,
      substances from which fats may be readily formed.

PMID- 19866917
TI  - A CONTRIBUTION TO THE KNOWLEDGE OF THE PATHOLOGY OF FRAGMENTATION AND
      SEGMENTATION, AND FIBROSIS OF THE MYOCARDIUM.

PMID- 19866919
TI  - A CASE OF SUSPECTED RABIES WITH ISOLATION OF BACILLUS DIPHTHERIAE FROM THE
      CENTRAL NERVOUS SYSTEM.

PMID- 19866918
TI  - CULTURES FROM THE BLOOD In SEPTICAEMIA, PNEUMONIA, MENINGITIS AND CHRONIC
      DISEASES.
AB  - OUR CONCLUSIONS FROM THE LITERATURE AND OUR OWN EXPERIMENTS MAY BE SUMMARIZED AS
      FOLLOWS: I. Blood for bacteriological examination during life should be taken
      directly from the veins and in considerable quantity. II. Resorption of toxines
      is the most important feature in cases of sepsis; pyogenie bacteria invade the
      general circulation in a rather small proportion even of severe eases, and, as a
      rule, late in the course of the disease. III. A general infection by the
      pnenmococcus can be demonstrated occasionally in the late stages of acute lobar
      pneumonia. IV. The value of blood cultures as a means of diagnosis in obscure
      cases of sepsis is limited by the fact that invasion of the blood by the specific
      organism cannot be demonstrated during life in the majority of cases. Positive
      cultures are very valuable; negative cultures do not exclude local septic
      infections. V. The detection of specific bacteria in the blood of cases of sepsis
      and of pneumonia gives a very unfavorable prognosis in most cases. VI. General
      terminal infections with pyogenic cocci occasionally occur as an immediate cause
      of death in chronic disease. Local infections processes play this part more
      frequently. VII. As far as our experiments have shown, invasion of the blood by
      bacteria during the death agony, with subsequent distribution of the genus to the
      organs by the circulation, is a rather uncommon occurrence. VIII. Owing to the
      relative infrequency of agonal invasion, we believe that in the majority of cases
      where the autopsy is performed promptly after death, the bacteria which are found
      in the organs succeeded in reaching these organs previously to the death agony,
      and are associated with the course of the disease. IX. The presence of bacteria
      in the organs of late autopsies is due in many cases to post-mortem extension
      from one organ to another, and in some cases to the post-mortem growth of small
      numbers of genus which were distributed to the organs by means of the
      circulation.

PMID- 19866920
TI  - AN EXPERIMENTAL INVESTIGATION OF THE TREATMENT OF WOUNDS OF THE HEART BY MEANS OF
      SUTURE OF THE HEART MUSCLE.
AB  - It would, of course, be incorrect to attempt to draw conclusions as to the
      dangers and the chances of success of suture of cardiac wounds in man from the
      results obtained by animal experimentation. Animals are placed in very
      unfavorable conditions after the operation. They are very restless and cannot be
      kept quiet. Ideal cleanliness is impossible and the animals may infect their
      wound by rubbing the external wound against the dirt on the floor of their cage.
      From the animal mortality in these investigations no rigid inferences applicable
      to human beings can therefore be made. Some conclusions of importance can,
      however, be drawn. Above all, my experiments seem to show that the mammalian
      heart will bear a much greater amount of manipulation than has hitherto been
      suspected. Very large wounds of the heart can heal and the healing process occurs
      in a manner entirely analogous to that in other muscular tissues. Even an
      extensive suture of the heart-wall of rabbits and dogs, although we know that
      thereby a large number of muscle fibres are destroyed and replaced by connective
      tissue, does not interfere with the function of the cardiac muscle as a whole.
      Can some of the results in the above recorded experiments be, with some
      restrictions of course, applied to the human heart? I think that this question
      must be answered in the affirmative. If we compare the knowledge we possess of
      wounds of the heart in man, with that obtained from animal experiments, and find
      that they agree in all essential particulars, then we are justified in reasoning
      by analogy that suture of wounds of the heart in man will give results similar to
      those obtained in the animal. In the last few decades, the advances made in all
      the branches of medicine-especially in pathology, bacteriology and surgery-have
      been due to a great extent to the generalization of the results of animal
      experimentation. To the careful and critical investigator, the results obtained
      in the animal experiment have always been of the greatest value in indicating to
      him the possibility of results to be obtained by similar procedures in the human
      body. From the study of wounds of the heart in man, and from the results obtained
      in my experiments, this conclusion seems therefore justified: wounds of the heart
      in man, when all other means have been tried and found wanting, can and ought to
      be closed by suture. The application itself of the suture is devoid of the one
      great danger that was feared in the past, i. e. of sudden arrest of the heart
      during the manipulations incident upon the application of the sutures. The number
      of sutures should be as small as possible so as to limit the amount of connective
      tissue which will be formed; for all the muscle fibres that are compressed by the
      sutures eventually atrophy and are replaced by new-formed connective tissue. It
      is probable that this connective tissue will not lead to degenerative changes in
      the heart-muscle. On the post-mortem table, fibrous plaques are often found in
      the otherwise normal human heart. In a number of the muscles of the body fibrous
      bands-tendinous intersections as they are called-are normally found. In the large
      number of microscopic sections of the heart-muscle that I have examined, I could
      find no evidence of pathological changes in the muscle fibres some distance from
      the scar. For similar reasons the suture should always be an interrupted one. We
      have shown that there are dangers and disadvantages in the continuous suture both
      on theoretical grounds and in practical use. The sutures should be passed through
      as little of the heart substance as possible; if they penetrate the epicardium
      and a small part of the thickness of the heart-muscle it will generally be
      sufficient. When the heart's action is not too rapid, each suture should be tied
      during a diastolic relaxation of the part under treatment. On this point we have
      not yet any experience in man. Cappelen, in his patient, tied the sutures during
      systole. Rehn tied them in his case during diastole. Only time and further
      experience will show how much importance is to be attached to this point. All
      that can be said, in the present state of our knowledge, is, that on theoretical
      grounds and from animal experimentation, it must be considered safest to tie the
      sutures during diastole. On first sight, it might appear difficult to apply
      sutures to an organ in such constant motion as is the heart. In practice,
      however, the difficulties have been proven not to be so great as might appear.
      The heart may be grasped with a forceps and the needle and suture easily passed.
      It is no more difficult to pass and tie a suture in a large dog than in a small
      rabbit. Hence we should infer that the difficulties of this procedure in the
      human heart, are not so great, a fact that has been borne out by the experience
      of those surgeons who have reported cases of heart-suture in man. The cases will
      always be few in which this extreme method of treatment-for so we must style it
      is necessary. Indeed, of the patients that come under the care of the surgeon,
      there are some who will recover from even large heart wounds without any local
      treatment at all. Cases have been recently reported by Conner, Brugnoli, Hamilton
      and others, where after wounds as large as three centimetres, the haemorrhage
      ceased spontaneously and the patients recovered. One cannot say, therefore, that
      wounds larger than a certain size must always be sutured. Each case must be
      carefully considered by itself. When we examine the nine cases of suture of the
      human heart in man (see pages 487 to 490) we cannot but hope for considerable
      success from this new method of surgical procedure. Of the nine cases, four
      recovered entirely, and four died of complications referable to other organs
      quite an encouraging record in a few cases. Finally, I may be permitted to
      summarize these conclusions as follows: 1. Suture of a wound of the heart as a
      final resort is an operation worthy of consideration in some cases and often
      justifiable. 2. Suture of wounds of the heart in animals, and also in man, is
      devoid of the danger of sudden arrest of the heart, due to the manipulation of
      the heart incident to the procedure, unless Kronecker's coordination centre be
      injured. 3. The suture should be an interrupted one of silk, applied in most
      cases so that the epicardium and superficial layers of the myocardium should be
      the only ones penetrated, and tied, when possible, during diastole. 4. No stated
      indications can be given as to the cases that are operable or the time when the
      operation should be done. Each case must be considered by itself for symptoms
      which would justify operative interference.

PMID- 19866921
TI  - A CASE OF ACUTE ENDOCARDITIS CAUSED BY MICROCOCCUS ZYMOGENES (NOV. SPEC.), WITH A
      DESCRIPTION OF THE MICROORGANISM.
AB  - From a case of acute endocarditis of the aortic and mitral valves with
      infarctions m the spleen and kidneys a micrococcus was twice isolated in pure
      culture from the blood during life and was demonstrated after death both
      microscopically and in pure culture in large numbers in the valvular vegetations,
      the infarctions and other parts. No other species of microorganism was found.
      This micrococcus is very small, occurs mainly in pairs, sometimes in short
      chains, stains by Gram's method, grows in small, pale, grayish-white colonies on
      gelatine and agar, at first clouds bouillon, which then becomes clear with a
      whitish sediment, does not produce gas in glucose media, liquefies gelatine
      slowly and to some extent also blood serum, and is especially characterized by
      its behavior in milk, which it acidifies, coagulates and subsequently liquefies.
      It produces a milk-curdling ferment and also a proteolytic ferment, each of which
      is separable from the bacterial cells. It remains viable for months in old
      cultures and is tolerably resistant to the action of heat and antiseptics. The
      micrococcus is pathogenic for mice and rabbits, causing either abscesses or
      general infections. Typical acute vegetative endocarditis was experimentally
      produced by intravenous inoculation of the organism in a rabbit and a dog, and
      the cocci were demonstrated in pure culture in the vegetations and other parts of
      these animals after death. Although the micrococcus here described has some
      points of resemblance to the pneumococcus and Streptococcus pyogenes on the one
      hand and to the pyogenic staphylococci on the other, it is readily distinguished
      from each of these species by cultural features which have been described and
      which are so obvious that the differentiation of these species from our
      micrococcus need not be discussed in detail. We have searched through the records
      concerning microorganisms described in association with endocarditis and other
      diseases, as well as those isolated from water, soil and other sources, and have
      been unable to find a description of a micrococcus identical in all particulars
      with that here described. Such points as staining by Gram, liquefaction of
      gelatine, coagulation and peptonization of milk, served singly or in combination
      to distinguish our micrococcus from other forms which in some respects might
      resemble it. We feel justified, therefore, in recognizing this organism as a new
      species and from its fermentative properties propose for it the name "Micrococcus
      zymogenes." Micrococcus zymogenes must be added to the already considerable list
      of bacteria which have been found as the specific infective agents in
      endocarditis. That it was the cause of this affection in our case was
      conclusively demonstrated by its repeated isolation in pure culture from the
      blood during life, by its presence in pure culture and large numbers after death
      in the cardiac vegetations, the infarctions, and other parts of the body, and by
      the experimental proof of its pathogenic properties, and notably its capacity to
      produce vegetative endocarditis by intravenous inoculation in animals.

PMID- 19866922
TI  - A STUDY OF THE NEURONE THEORY.

PMID- 19866923
TI  - A CONTRIBUTION TO THE SUBJECTS OF CHRONIC INTERSTITIAL NEPHRITIS AND ARTERITIS IN
      THE YOUNG, AND FAMILY NEPHRITIS; WITH A NOTE ON CALCIFICATION IN THE LIVER.

PMID- 19866924
TI  - LYMPHOMA, A BENIGN TUMOR REPRESENTING A LYMPH GLAND IN STRUCTURE.

PMID- 19866925
TI  - OBSERVATIONS CONCERNING LEUKAEEMIC LESIONS OF THE SKIN.

PMID- 19866926
TI  - A CASE OF ADDISON'S DISEASE WITH SIMPLE ATROPHY OF THE ADRENALS.

PMID- 19866928
TI  - ON THE DIFFERENTIATION AND CLASSIFICATION OF WATER BACTERIA.

PMID- 19866927
TI  - A PECULIAR FORM OF FIBROSARCOMA OF THE BRAIN.

PMID- 19866929
TI  - BACILLUS PYOCYANEUS AND ITS PIGMENTS.
AB  - THE PRINCIPAL CONCLUSIONS THAT SEEM TO ME JUSTIFIED ARE AS FOLLOWS: 1. The
      fluorescent pigment formed by some varieties of B. pyocyaneus is produced under
      conditions identical with those governing the production of the pigment by other
      "fluorescent bacteria." 2. The production of pyocyanin is not dependent upon the
      presence of either phosphate or sulfate in the culture medium. It is formed in
      non-proteid as well as in proteid media, but is not a necessary accompaniment of
      the metabolic activities of the organism (e. g. tartrate solution). 3. The power
      of producing pyocyanin under conditions of artificial cultivation is lost sooner
      than the fluorescigenic power. 4. There are greater natural and acquired
      differences in pyocyanigenic power than in fluorescigenic. 5. The fluorescent
      pigment may be oxidized slowly by the action of light and air as well as by
      reagents into a yellow pigment, and pyocyanin may be similarly oxidized into a
      black pigment. 6. A convenient separation of B. pyocyaneus into four varieties
      would be the following: var. alpha, pyocyanigenic and fluorescigenic (most
      common); var. beta, pyocyanigenic only (rare); var. gamma, fluorescigenic only
      (not uncommon, closely related to "B. fluorescens liquefaciens"); var. delta, non
      chromogenic. 7. Except for the occasional loss of one or another function the
      different varieties are not so plastic as sometimes assumed, and cannot be
      readily converted into one another by subjection to varying conditions of life.
      8. The signification and correlation of the almost countless physiological
      variations among the members of this group in respect to growth in gelatin,
      behavior to temperature, indol production, etc., remain to be determined. It is
      not yet clear that the variations in chromogenic power can be in any way
      correlated with the presence or absence of other physiological functions.

PMID- 19866930
TI  - A PRELIMINARY NOTE ON THE FRACTIONAL PRECIPITATION OF THE GLOBULIN AND ALBUMIN OF
      NORMAL HORSE'S SERUM AND DIPHTHERIC ANTITOXIC SERUM, AND THE ANTITOXIC STRENGTH
      OF THE PRECIPITATES.

PMID- 19866932
TI  - A CONTRIBUTION TO STAINING METHODS : I. A DIFFERENTIAL STAIN FOR CONNECTIVE
      TISSUE FIBRILLAE AND RETICULUM. II. CHLORIDE OF IRON HAEMATOXYLIN FOR NUCLEI AND
      FIBRIN. III. PHOSPHOTUNGSTIC ACID HAEMATOXYLIN FOR NEUROGLIA FIBRES.

PMID- 19866931
TI  - PROLIFERATION AND PHAGOGYTOSIS.

PMID- 19866933
TI  - A STUDY OF THE NEUROFIBRILS IS THE GANGLION CELLS OF THE CEREBRAL CORTEX.

PMID- 19866934
TI  - AN EXPERIMENTAL STUDY OF OXALURIA, WITH SPECIAL REFERENCE TO ITS FERMENTATIVE
      ORIGIN.
AB  - 1. As varying amounts of calcium oxalate may be held in solution in the urine,
      conclusions based upon the presence or number of calcium oxalate crystals found
      therein are of no real value as an indication of the quantity of oxalic acid
      present. 2. Unless the utmost care is exercised, the results obtained by
      quantitative estimation of oxalic acid are subject to large percentages of error.
      This is especially true in the use of Neubauer's or Shultzen's methods, in which
      the calcium oxalate is precipitated in an alkaline solution. 3. An ordinary mixed
      diet regularly contains traces of oxalic acid or its salts. 4. A portion of the
      oxalic acid ingested with the food may be absorbed and reappear unchanged in the
      urine. 5. The normal daily excretion of oxalic acid in the urine fluctuates with
      the amount taken in the food, and varies from a few milligrammes to two or three
      centigrammes, being usually below ten milligrammes. 6. In health, no oxalic acid,
      or only a trace, is formed in the body, but that present in the urine has been
      ingested with the food. 7. In certain clinical disturbances which in some of the
      cases studied above were associated with absence of free hydrochloric acid from
      the gastric juice, oxalic acid is formed in the organism. 8. This formation in
      the organism is connected with fermentative activity in the alimentary canal. (a)
      The prolonged feeding of dogs with excessive quantities of glucose, together with
      meat, leads eventually to a state of oxaluria. (6) This experimental oxaluria is
      associated with a mucous gastritis, and with absence of free hydrochloric acid in
      the gastric contents. (c) The oxaluria and the accompanying gastritis are
      referable to fermentation induced by the excessive feeding with sugar. (d) The
      experimental gastritis from fermentation is associated with the formation of
      oxalic acid in the gastric contents. 9. The symptoms attributed to an oxalic acid
      diathesis, with the exception of those due to local irritation in the
      genitourinary tract, do not appear to be due to the presence in the system of
      soluble oxalates, but are more likely to depend on other products of fermentation
      and putrefaction.

PMID- 19866935
TI  - SERUM-GLOBULIN AND DIPHTHERIC ANTITOXIN.-A COMPARATIVE STUDY OF THE AMOUNT OE
      GLOBULIN IN NORMAL AND ANTITOXIC SERA, AND THE RELATION OF THE GLOBULINS TO THE
      ANTITOXIC BODIES.
AB  - THE RESULTS OF THE FOREGOING EXPERIMENTS MAY BE BRIEFLY SUMMARIZED AS FOLLOWS:
      The amount of antitoxic substance obtained by precipitation with magnesium
      sulphate from the blood-serum of the horse corresponds, as nearly as can be
      determined by the use of test guinea-pigs, in full to the protective power of the
      serum from which it is obtained, i. e. the precipitate from 1 cc. of serum will
      protect against the same amount of toxin as 1 cc. of the serum itself. Equal
      amounts of the precipitates by magnesium sulphate from immunized and non
      immunized horses act differently toward toxin; i. e. the proportion of protective
      substance to the precipitate from non-immunized serum is exceedingly small as
      compared with the proportion of antitoxin to the precipitate from sera of
      immunized horses. The average precipitate from the sera of immunized horses, as
      obtained by magnesium sulphate, is more abundant than the average precipitate
      from sera of non-immunized horses. In the case of the same animal before and
      after immunization, the serum before immunization gives a less abundant
      precipitate with magnesium sulphate than the serum tested after immunization. The
      proportion of increase per unit of antitoxic strength for the same or different
      horses is not constant. This may be due to an increase of inactive substances (in
      their relation to diphtheric toxin) or to imperfect methods of determination. The
      precipitates obtained by magnesium sulphate give all the reactions recognized as
      characteristic of globulins, and as distinguishing them from other albuminous
      bodies. We are not warranted, then, in the present state of our knowledge, in
      considering any part of these precipitates as other than globulin. But it does
      seem warrantable to conclude, from the fact that the globulins of normal serum do
      not protect, or only in comparatively large amounts, against diphtheric toxin,
      that new globulins are formed, or rather greatly increased in the serum of
      immunized horses, and that these globulins protect against the toxin. These
      increased globulins and the inert globulins (which from obvious causes are a very
      variable factor) are both precipitated by magnesium sulphate. Every animal has a
      physiological and pathological history more or less widely diverging from the
      normal, hence absolute conformity in the results obtained is not to be expected,
      at least with our present methods of differentiation.

PMID- 19866936
TI  - THE FRACTIONAL PRECIPITATION OF THE GLOBULIN AND ALBUMIN OF NORMAL HORSE'S SERUM
      AND DIPHTHERIA ANTITOXIC SERUM, AND THE ANTITOXIC STRENGTH OF THE PRECIPITATES.
AB  - 1. The globulins of both normal and diphtheria antitoxic serum exhibit chemically
      toward reagents the same reactions, being precipitated by magnesium sulphate and
      split up into fractions in precisely the same way. 2. All of the diphtheric
      antitoxic power of both normal and immunized serum is always carried by the
      globulin and its fractional precipitates. 3. During the fractional precipitation
      of the serum globulin of horses immunized from diphtheria toxin and horses not
      immunized from diphtheria toxin, some of the globulin is lost, likewise at the
      same time some of the antitoxic power of the globulin of the immunized serum is
      lost. 4. These reactions, considered in connection with the fact that different
      observers as well as we ourselves have found diphtheric antitoxic power in normal
      horse's serum and that this antitoxin separates with the globulin, strongly
      incline us to consider "diphtheria antitoxin" a form of globulin. 5. The
      reactions of globulin, previously separated from the serum by magnesium sulphate,
      with sodium chloride lead one to think that there is a formation of globulin
      salts. 6. Since serum albumin in a magnesium sulphate solution gives fractional
      precipitates at definite temperatures, it seems not improbable that the albumin
      is precipitated in the form of albumin salts.

PMID- 19866937
TI  - REFRACTORY SUBCUTANEOUS ABSCESSES CAUSED BY SPOROTHRIX SCHENCKII. A NEW
      PATHOGENIC FUNGUS.

PMID- 19866938
TI  - PATHOLOGICAL REPORT ON A CASE OF DERMATITIS VESICULO-BULLOSA ET GANGRAENOSA
      MUTILANS MANUUM (DUHRING), WITH A CONSIDERATION OF THE RELATIONS OF VASCULAR AND
      NERVOUS CHANGES TO SPONTANEOUS GANGRENE AND RAY NAUD'S DISEASE.

PMID- 19866939
TI  - AMYLOID SUBSTANCE AND AMYLACEOUS BODIES IN MULITIPIE SYPHILITIC TUMORS OF THE
      BONES, WITH REMARKS ON THE RELATION OF AMYLACEOUS BODIES TO AMYLOID SUBSTANCE.

PMID- 19866940
TI  - ON THE PRESENCE OF NEW ELASTIC FIBRES IN TUMORS.

PMID- 19866941
TI  - A CASE OF GENERAL GASEOUS EMPHYSEMA WITH GAS CYSTS IN THE BRAIN FORMED AFTER
      DEATH AND DUE TO BACILLUS MUCOSUS CAPSULATUS, WITH A CONSIDERATION OF THE GAS
      PRODUCING PROPERTIES OF CERTAIN MEMBERS OF THIS GROUP IN THE CADAVERS OF ANIMALS.
AB  - In the case reported in this article there was septicaemia with special
      localization of the microorganisms in the brain, with gas cysts of the brain and
      general gaseous emphysema due to Bacillus mucosus capsulatus (aerogenes group).
      The bacillus isolated from the organs of this case, as well as other members of
      the aerogenic group of Bacillus mucosus capsulatus can cause general gaseous
      emphysema in the cadavers of rabbits, either with or without the intravenous
      injection of sugar before the animal is killed, the gas, however, being most
      abundant and rapidly formed in the former case. It is not impossible that some of
      the published cases of gaseous emphysema in which a bacteriological examination
      was not made, may have been due to members of the Bacillus mucosus capsulatus
      group.

PMID- 19866942
TI  - TWO CASES OF NECROTIC BRONCHO-PNEUMONIA WITH STREPTOTHRIX.

PMID- 19866943
TI  - ACUTE INTERNAL HYDEOCEPHALUS. A CLINICAL AND PATHOLOGICAL STUDY.

PMID- 19866944
TI  - A PRELIMINARY REPORT ON ACID-RESISTING BACILLI, WITH SPECIAL REFERENCE TO THEIR
      OCCURRENCE IN THE LOWER ANIMALS.
AB  - THE RESULTS OBTAINED IN THIS STUDY MAY BE BRIEFLY SUMMARIZED: 1. Acid-resisting
      bacilli are found in many of the lower animals, more especially the horse, cow,
      dog, guinea-pig and white rat. In the case of the rabbit and cat no such
      organisms were detected. 2. Many of these acid-resisting bacilli resemble the
      tubercle bacillus and the smegma bacillus of man. 3. The acid-resisting organisms
      are undoubtedly of different species and there is good reason to believe that the
      term smegma bacillus denotes not a definite species but rather a group of bacilli
      having common staining properties.

PMID- 19866945
TI  - A COMPARATIVE STUDY OF THE BIOLOGICAL CHARACTERS AND PATHOGENESIS OF BACILLUS X
      (STERNBERG), BACILLUS ICTEROIDES (SANARELLI), AND THE HOG-CHOLERA BACILLUS
      (SALMON AND SMITH).
AB  - 1. Bacillus X (Sternberg) belongs to the colon group. 2. Bacillus icteroides
      (Sanarelli) is a member of the hog-cholera group. 3. The various channels of
      infection, the duration of the disease and the gross and microscopical lesions in
      mice, guinea-pigs and rabbits are the same for Bacillus icteroides and the hog
      cholera bacillus. 4. The clinical symptoms and the lesions observed in dogs
      inoculated intravenously with Bacillus icteroides, are reproduced in these
      animals by infection with the hog-cholera bacillus. 5. Bacillus icteroides when
      fed to the domestic pig causes fatal infection, accompanied by diphtheritic,
      necrotic and ulcerative lesions in the digestive tract, such as are seen in hogs
      when infected with the hog-cholera bacillus. 6. This disease may be acquired by
      exposing swine in pens already infected with Bacillus icteroides, or by feeding
      them with the viscera of infected pigs. 7. Guinea-pigs may be immunized with
      sterilized cultures ofBacillus icteroides from a fatal dose of the hog-cholera
      bacillus and vice versa. 8. Rabbits may be rendered immune by gradually
      increasing doses of a living culture of Bacillus icteroides of weak virulence
      from a fatal dose of a virulent culture of the hog-cholera bacillus 9. The sera
      of animals immunized with Bacillus icteroides and with the hog-cholera bacillus,
      respectively, show a marked reciprocal agglutinative reaction. 10. While the
      blood of yellow fever practically does not exercise an agglutinative reaction
      upon Bacillus icteroides, the blood of hog-cholera agglutinates this bacillus in
      a much more marked degree, thus pointing, we think, to the closer etiological
      relationship of this bacillus to hog-cholera than to yellow fever.

PMID- 19866946
TI  - SOME OBSERVATIONS UPON THE BACTERIAL SELF-PURIFICATION OF STREAMS.

PMID- 19866947
TI  - ON THE TOXICITY OF NORMAL URINE.

PMID- 19866949
TI  - FALSE DIVERTICULA OF THE INTESTINE.

PMID- 19866948
TI  - THE SUPERFICIAL GLANDS OF THE GESOPHAGUS.

PMID- 19866950
TI  - SOME THEORETICAL CONSIDERATIONS UPON THE NATURE OE AGGLUTININS, TOGETHER WITH
      FURTHER OBSERVATIONS UPON BACILLUS TYPHI ABDOMINALIS, BACILLUS ENTERITIDIS,
      BACILLUS COLI COMMUNIS, BACILLUS LACTIS AEROGENES, AND SOME OTHER BACILLI OF
      ALLIED CHARACTER.

PMID- 19866951
TI  - REPORT OF A LABORATORY EPIZOOTIC AMONG-GUINEA-PIGS, ASSOCIATED WITH GASEOUS
      EMPHYSEMA OF THE LIVER, SPLEEN AND KIDNEYS, DUE TO BACILLUS MUCOSUS OAPSULATUS.

PMID- 19866953
TI  - MALARIAL PARASITOLOGY.

PMID- 19866952
TI  - ON THE RELATION OF CHRONIC INTERSTITIAL PANCREATITIS TO THE ISLANDS OF LANGERHANS
      AND TO DIABETES MELUTUS.
AB  - (1) Congenital syphilitic pancreatitis retards the development of the glandular
      acini but does not affect the islands of Langerhans. Embedded in the stroma, but
      not invaded by it, the latter maintain their continuity with the small ducts and
      acini with which they have a common origin. (2) Two types of chronic interstitial
      inflammation affecting the developed pancreas are distinguishable: (a)
      Interlobular Pancreatitis.-In the interlobular variety the inflammatory process
      is localized chiefly at the periphery of the lobule and implicates the islands of
      Langerhans only when the sclerotic process has reached a very advanced grade.
      When pancreatitis has followed obstruction of the ducts, the islands long remain
      unaltered though embedded in dense scar-like tissue. (b) Interacinar
      Pancreatitis.-In the interacinar type the process is diffuse, invading the
      lobules and separating individual acini. The inflammatory change invades the
      islands of Langerhans. (3) A relationship has been observed between lesions of
      the islands of Langerhans and the occurrence of diabetes mellitus. (a) In one of
      eleven cases of interlobular panereatitis diabetes of mild intensity occurred.
      The sclerosis, which in this case followed obstruction of the ducts by calculi,
      was far advanced and affected the islands of Langerhans. (b) In two of three
      cases of interacinar pancreatitis, diabetes was present. The third case was
      associated with a condition, haemochromatosis, which at a later stage is
      associated with diabetes, the result of pancreatic lesion. (c) In a fourth case
      of diabetes, hyaline deposit between the capillaries and the parenchymatous cells
      had so completely altered the islands of Langerhans that they were no longer
      recognizable.

PMID- 19866954
TI  - THE NERVES OF THE CAPILLARIES, WITH REMARKS ON NERVE-ENDINGS IN MUSCLE : A NEW
      THEORY OF LYMPH-FORMATION AND OF GLANDULAR SECRETION.
AB  - 1. The endings of the motor nerves in striped muscle remain on the outside of the
      sarcolemma. Aside from the surfaces of contact of muscle and nerve fibre, the end
      fibres are covered down to their tips with the sheath of Schwann and are provided
      with nuclei. The precise condition of things at the places of contact of muscle
      and nerve is an unsolved problem of histology. 2. The ivy-like or festooned
      arrangement of motor nerves in the frog's muscle has been misinterpreted.
      Properly interpreted it demonstrates that the nerve fibres that are to influence
      the muscle fibre are not naked and that they need not be end fibres. It shows
      that mere contact between muscle fibre and nerve fibre is all that is necessary.
      3. The sheath of Henle in the frog and in the smaller muscle fibres of the snake
      is open, thus permitting escape of the cerebrospinal fluid. 4. In other animals
      Henle's sheath extends over the end fibres of the motor nerve and the cells
      lining it envelop the end fibrils. I find that the so-called "Sohlensubstanz" of
      Kuhne is derived from the cells of Henle's sheath. 5. The terminal nerves in
      smooth muscle form a network entwining the bundles of muscle fibres. I consider
      it improbable that each plain muscle fibre has a special terminal nerve fibril.
      6. In muscular tissue fine non-medullated nerves, probably belonging to the
      centrifugal, vasomotor system, proceed from the fasciculi of motor nerves. These
      nerves can be traced directly to a network of nerves surrounding the capillaries.
      From this network fine, nucleated, nerve fibres pass to the walls of the
      capillaries, with which they are very closely united. 7. The nerves supplying the
      capillaries connect also with sensory nerves and with nerves surrounding the
      larger blood-vessels, both arteries and veins. 8. The branches of the chorda
      tympani in the submaxillary gland do not pass to the gland cells, but they
      terminate on the capillaries. 9. In muscular and glandular tissues-and perhaps
      throughout the body-there is a vast peripheral nervous plexus belonging to the
      capillary blood-vessels. These nerves of the capillaries, which may perhaps be
      regarded as nutritive nerves, regulate the production and transudation of lymph,
      and are concerned in the mechanism of glandular secretion. They may be called
      into activity both by peripheral influences and by impulses received from the
      central nervous system and the sympathetic ganglia. They may influence, through
      their connections with the vasomotor nerves on the arteries and veins, the blood
      supply to a part.

PMID- 19866955
TI  - THE INFLUENCE OF BILE ON METABOLISM.
AB  - 1. Bile increases the digestion of fat when given by the mouth in pill form. The
      percentage of fat lost in the stools of our patient with a complete biliary
      fistula was 63 per cent in the first period and 57 per cent in the third. This
      closely corresponds to the results that Muller obtained in human beings and dogs
      with complete obstruction of the common duct. Under bile medication the stools
      contained 23 per cent less fat than in the first period, and 17 per cent less
      than in the third. This represents an actual diminution of the amount of fat lost
      in the stools. Looking at the result in another way, it may be said that the
      average digestion of fat in the periods without bile was 40 per cent; in the
      periods with bile, 60 per cent, i. e., bile increased the digestion of fat
      relatively by 50 per cent. 2. The digestion of nitrogenous food is improved by
      the use of bile pills when the amount of fat in the stools is large. Instead of
      an average of 15 per cent being lost in the faeces, but 7 per cent escaped
      digestion during the four days the patient took bile. The reason for this,
      perhaps, lies in the better digestion of fat at this time, in consequence of
      which the proteid elements of the food were more thoroughly exposed to the
      digestive juices. 3. Ox bile is a cholagogue. The amount of bile-solids secreted
      in the bile period was 47 per cent greater than in the periods before and after.
      This confirms the work of Pfaff and Balch, here in Boston, on a human being, and
      that of Stadelmann and his pupils, in Germany, on dogs. 4. The effect of the bile
      on the bowels in this case was not remarkable, although they moved more
      satisfactorily during the bile period. In my experiments with dogs I usually
      obtained diarrhoea when giving bile. I do not feel sure, however, that this
      should be attributed wholly to the medication, for the diarrhoeas as a rule
      appeared six or more days after the beginning of the experiment and the animals
      were then in poor condition. Dr. Pfaff, who has had more experience with the
      administration of bile than I, tells me that he has found its action variable in
      patients. In some cases it is a laxative; in others, in which there is diarrhoea,
      due apparently to large amounts of fat in the food, it has the opposite effect.
      5. As to the general effect of bile on body metabolism, it was observed that the
      urea and nitrogen were excreted in greater amount in the bile period than in
      either of the others. No definite conclusions can be drawn from this fact,
      because more nitrogen was ingested during these four days; moreover, it must be
      borne in mind that in these results the salol may have been a factor. 6. The
      amount of urine was increased by more than 50 per cent in the bile period. It is
      interesting to note that the amount was about the same during this bile period as
      in the second experiment when the bile was again taking its natural course. Von
      Noorden has recorded a similar increase in the amount of urine following the
      removal of the obstruction in acute catarrhal jaundice. The salol coating of the
      bile pills, which amounted to one and a quarter grammes a day, is not sufficient
      to account for this effect. This is evident from the work of Kumagawa, who gave
      two grammes of sodium salicylate daily to a dog of 25 kilos without essentially
      changing the amount of urine secreted. On the other hand, in taking the 30 pills
      daily the patient drank several extra glasses of water, and in the second
      experiment her general condition was naturally better than at any other time.

PMID- 19866956
TI  - THE RELATION OE DIABETES MELLITUS TO LESIONS OF THE PANCREAS. HYALINE
      DEGENERATION OF THE ISLANDS OE LANGERHANS.

PMID- 19866957
TI  - ALLOXURIC EXCRETION IN A CASE OF LEUCOPENIA.
AB  - 1. In the case investigated, one of Malta fever, the leucocytes were reduced to
      between 1500 and 3000 per cubic millimetre. 2. Notwithstanding this, the alloxur
      bodies and the phosphoric acid in the urine, the patient being on an alloxur-free
      diet, showed no distinct diminution from the normal. 3. The suggestion is made
      that this result may be due to the leucopenia being brought about by an increased
      destruction of leucocytes in the spleen rather than to a diminished activity of
      the bone-marrow.

PMID- 19866958
TI  - STUDIES ON THE MORPHOLOGY OF GANGLION CELLS IN THE RABBIT : I. THE NORMAL NERVE
      CELLS. II. CHANGES IS THE NERVE CELLS IN RABIES.

PMID- 19866959
TI  - THE ACID INTOXICATION OF DIABETES IN ITS RELATION TO PROGNOSIS.
AB  - IT SEEMS DESIRABLE TO EMPHASIZE THE FOLLOWING CONCLUSIONS: 1. A careful balancing
      of the normal acids and bases of the urine makes it possible not merely to detect
      the presence of organic acids in the urine, but also to determine approximately
      the amount of such acids. The method recently described by Herter and Wakeman can
      be recommended as securing a greater degree of accuracy, for the amount of labor
      involved, than any other procedure. 2. The determination of the N of NH(3) is a
      useful procedure for clinical purposes, since it is probably true that a
      considerable excretion of organic acid (say 15 gm. oxybutyric or more in 24
      hours) is always attended by an increased excretion of NH(3). As much organic
      acid as corresponds to 10 gm. oxybutyric acid may be excreted in 24 hours without
      causing an increased excretion of NH(3) (Case IX). We cannot therefore rely on
      the ammonia output to detect moderate quantities of organic acid. 3. Where
      organic acids are removed in considerable amount without increasing the excretion
      of NH(3), the acid takes out other alkalies, probably in some instances chiefly
      K. 4. In cases of diabetic coma the urine always contains a large excess of
      organic acids and the N of NH(3) is usually increased to 18 to 25 per cent of the
      total N. 5. Crotonic acid can regularly be obtained from the urines of patients
      in diabetic coma. 6. The condition of diabetic coma is preceded by a period of
      days, weeks or months, in which there is a large excretion of beta-oxybutyric
      acid (20 gm. or more in 24 hours), and in which the N of NH(3) is largely
      increased. 7. Patients whose urines show or have shown a large excretion of
      organic acids are in danger of developing diabetic coma, but the N of NH(3) may
      temporarily rise as high as 16 per cent and yet coma may be delayed for more than
      7 months (Case VII). The persistent excretion of more than 25 gm. of beta
      oxybutyric acid indicates impending coma. 8. A patient passing 30 gm. of beta
      oxybutyric acid in 24 hours may still have enough energy and strength to be about
      all day and perform considerable muscular work (Case X). 9. A patient who has
      been excreting very little organic acid and has gained weight may within a few
      months show the presence of considerable quantities of organic acid, and die in
      typical diabetic coma (Case VII). 10. When the urine contains little or no
      organic acid there is no immediate prospect of diabetic coma, but patients with
      such urine are probably liable to most of the other dangers that threaten
      diabetic patients. The relation between the degree of acid intoxication and the
      susceptibility to infection seems worthy of special experimental study. 11. Where
      the urine regularly contains more than 200 gm. of sugar per day there is usually
      considerable organic acid in the urine and large amounts of acid, indicative of
      coma, are invariably accompanied by considerable or great glycosuria. 12.
      Sometimes there is much sugar and little or no acid in the urine, and sometimes
      there is considerable acid and little sugar. These facts render it desirable to
      examine the urine of diabetic patients at least once a month with reference to
      the amount of acid excreted, for the element of acid intoxication must be clearly
      separated from the element of glycosuria in our study of the progress of a case.
      In other words, we must recognize the acid intoxication as an important and
      sometimes as a dominant factor in the prognosis, and this element should be
      regarded even in those cases of diabetes which have the clinical indications of a
      mild type of the disease. We may thus hope to prolong life in many instances by
      taking precautions, as to diet and out-of-door life, which might not otherwise be
      deemed necessary. 13. The withdrawal of carbohydrate food frequently leads to a
      considerable reduction in the quantity of organic acids excreted. The reason for
      this is not yet clear and the phenomenon deserves careful study.

PMID- 19866960
TI  - NOTES UPON THE AGGLUTINATIONS OBTAINED BY INTRAPERITONEAL INSERTION OF CELLOIDIN
      CAPSULES CONTAINING BACILLI AND UPON A MODE OF PREPARING SUCH CAPSULES.
AB  - 1. Capsules made as described above allow dialysis, when placed in the peritoneal
      cavity. 2. The normal tissues, unstimulated, do not possess the power of causing
      agglutination; they do not require to be stimulated by the presence of the
      bacterial bodies, but will produce their share of the agglutinins when acted upon
      by the bacillary products. 3. Agglutination follows the insertion, in the
      peritoneal cavity, of "capsuled" bacilli; it gradually increases in degree, and
      on the removal of the capsule containing the bacilli, begins to disappear. 4.
      Varieties of bacilli, related closely in morphology and cultural reactions, do
      not, as a rule, produce serums which inter-agglutinate.

PMID- 19866961
TI  - SOME EXPERIMENTAL DATA ON THE SIGNIFICANCE OF CONCENTRATION AND OF MULTIPLICITY
      OF AREA IN HYPODERMIC INJECTIONS.

PMID- 19866962
TI  - OBSERVATIONS ON A CASE OF CYCLIC ALBUMINURIA.
AB  - The preceding observations record a new instance of the occurrence of cyclic
      albuminuria in an otherwise apparently healthy young man. The typical course of
      the proteid excretion from hour to hour under various conditions has been
      reviewed and its independence of the changes in diet or muscular work pointed
      out. No relationship between the volume of urine eliminated and the quantity of
      proteid excreted has been ascertained. The specific effect of the horizontal
      posture in dispelling the albuminuria is the most interesting feature observed.
      The attempt to refer this to attendant circulatory changes in the kidneys is, for
      the present, no more than an interesting speculation. See PDF for Structure See
      PDF for Structure.

PMID- 19866963
TI  - THE PRODUCTION OF SARCOSPORIDIOSIS IN THE MOUSE BY FEEDING INFECTED MUSCULAR
      TISSUE.

PMID- 19866964
TI  - A STUDY OF CHRONIC HYPERPLASTIC TUBERCULOSIS OF THE INTESTINE, WITH REPORT OF A
      CASE.

PMID- 19866965
TI  - A CASE OF MULTIPLE MYELOMA.

PMID- 19866966
TI  - ACUTE EPIZOOTIC LEUCOENCEPHALITIS IN HORSES.

PMID- 19866967
TI  - ON THE OCCURRENCE OF STRONGYLOIDES INTESTINALIS IN THE UNITED STATES.

PMID- 19866968
TI  - THE EFFECTS OF SUBMINIMUM DOSES OF STRYCHNINE IN NEPHRECTOMIZED RABBITS.

PMID- 19866969
TI  - CONTRIBUTION TO THE PATHOLOGICAL ANATOMY OF MALARIAL FEVER.

PMID- 19866970
TI  - THE ETIOLOGY OF ACUTE DYSENTERY IN THE UNITED STATES.
AB  - 1. The several standard cultures used in this study are indistinguishable -a
      conclusion previously reached and stated by Flexner. 2. The acute dysentery of
      the United States is due to a bacillus indistinguishable from that obtained from
      the epidemics of dysentery in several other parts of the world. 3. The sporadic
      and the institutional outbreaks of acute dysentery are caused by the same
      microorganism, and this organism is identical with that causing epidemic acute
      dysentery. 4. The cause of acute dysentery, whether sporadic, institutional, or
      epidemic, is Bacillus dysenteriae Shiga.

PMID- 19866971
TI  - EXPERIMENTS ON THE EFFECTS OF INJECTION OF EGG-ALBUMEN AND SOME OTHER PROTEIDS.
AB  - THE CONCLUSIONS WHICH WE DERIVE FROM OUR OBSERVATIONS ARE AS FOLLOWS: 1. The
      excretion of injected, egg-albumen as such is in no case complete. The quantity
      retained varies from 23 to 100%. 2. The amount retained varies: a) directly with
      the slowness of absorption. This is determined by the manner of administration.
      b) directly with the time during which the proteid remains in the body; and
      therefore inversely to the rapidity of excretion. c) inversely to the quantity
      injected; this has however much less effect than (a) or (b). d) with individual
      peculiarities; but these are not very conspicuous. 3. The excreted proteid
      coagulates at the same temperatures as the injected albumen. 4. Injection of egg
      albumen does not cause the appearance of globulins in the urine. 5. The
      proportion of proteid coagulating at lower temperatures is less in the urine than
      in the injected solution. When a solution has been heated to 73 degrees before
      injection, the urine also does not coagulate below this temperature. 6. Egg
      albumen injected into the hen is excreted as with mammals. 7. The albuminuria
      lasts in typical cases from 1(1/2) to 3 days, according to the manner of
      administration. The excretion begins very shortly (7 minutes) after injection. 37
      per cent of the total proteid injected may be excreted in an hour. About three
      fourths of the total excretion takes place within the first 17 hours; the
      excretion is almost completed in the next 15 hours, only traces being excreted
      thereafter. With hypodermic injection the amount is more nearly equal on 2 or 3
      successive days, since the absorption may extend over 2 days. 8. Alkali-albumin,
      as well as muscle-proteids (from foreign species) are completely retained. An
      unconverted mixture of egg-albumen and sodium carbonate behaves like egg-albumen.
      9. A small amount of proteid (less than 5%) is excreted unchanged by the faeces.
      10. A variable proportion is excreted as non-coagulable proteid. The quantity of
      this is proportional to that of the coagulable proteid of the urine. 11. The rest
      undergoes complete metabolism to urea. 12. The total nitrogen excretion is
      increased beyond the amount of nitrogen introduced as albumen. 13. Starvation
      appears to cause an increase in the ratio of the urea to the total nitrogen of
      the urine. 14. The effects of intravenous injection of egg-albumen on circulation
      and respiration do not differ from those of an equivalent injection of the
      solvent. Albumen causes, however, a specific diuresis, beginning 50 minutes after
      the intravenous injection, and reaching its maximum in about 2 hours. It causes
      neither glycosuria nor haemoglobinuria. 15. The injection of egg-albumen,
      alkaline egg-syntonin, or muscle extracts, causes in rabbits a rise of
      temperature of 1 to 2 degrees C. This begins in about an hour, usually reaches
      its maximum in from 6 to 8 hours, and then falls rapidly. It may in rare cases
      persist for several days. It is indifferent qualitatively whether the injection
      is made by the jugular or the ear-vein, hypodermically, or into the peritoneum.
      Even extremely small quantities injected into the ear-vein cause this rise. The
      fever does not cause histological alterations in any organ examined. The
      injection of normal salt solution may cause a rise, but this is much smaller. 16.
      The injection of egg-albumen causes but very slight histological changes. The
      kidneys are usually congested, especially in the cortex. The cells may be
      slightly cloudy. A slight degree of nephritis may occur, but this is not of such
      degree as to effect permanent lesions. The injection of muscle extracts may give
      rise to a more pronounced parenchymatous nephritis. 17. Urethane is fatal to
      rabbits in doses of 0.75 to 1.0 grm. per kilo. The symptoms consist mainly in a
      very marked fall of temperature, and in medullary paralysis. 0.5 grm. per kilo.
      lowers the temperature 2.3 degrees C. Doses as small as 0.6 grm. per kilo cause
      very marked histological changes, consisting mainly in extensive granular and
      vacuolar degeneration of the hepatic epithelium, which are so acute as to be
      fully developed when death occurs in 1(1/2) hours after injection. Doses of 0.35
      grm. per kilo. do not produce this change. Chloretone did not cause the
      degeneration, but is followed by congestion of the abdominal viscera. 18. Native
      egg-albumen, injected into the femoral vein of a dog, was followed in one case by
      a fatal ending with convulsions and coma, after several intervening cases of good
      health. Further experiments demonstrated that there is no toxicity inherent in
      fresh egg-albumen, nor can it be developed by breeding the eggs in the shell. The
      cause of the above fatal issue must therefore be sought in some extraneous toxic
      agent which contaminated the solution. Muscle-extracts were also devoid of
      toxicity. Alkali-albumin produces no changes beyond those which may be attributed
      to the free alkali contained therein.

PMID- 19866972
TI  - A CONTRIBUTION TO OUR KNOWLEDGE OF THE ACTION OF SAPONIN ON THE BLOOD CORPUSCLES
      AND PUS CORPUSCLES.
AB  - 1. The increase of conductivity produced by saponin in formaldehyde-hardened
      blood is due to an increase in the conductivity of the corpuscles (increased
      permeability of the corpuscles to ions) and not, mainly at any rate, to the
      liberation of electrolytes from the corpuscles and a consequent increase in the
      conductivity of the serum. The increase in the permeability of the corpuscles is
      probably caused by a "corrosive," dissolving, or emulsifying action of the
      saponin on some non-proteid constituent of the envelope or stroma. 2. In the
      first stage of the action of saponin on blood (not fixed by formaldehyde) there
      seems also to be an increase in the permeability of the corpuscles for ions, even
      before any haemoglobin has been liberated. The liberation of the haemoglobin may
      be secondary to this, owing to the entrance, of water consequent on the
      disturbance of osmotic equilibrium. 3. Heating the blood to 40 degrees to 45
      degrees C. intensifies the laking action of saponin, so that a dose insufficient
      to cause laking at ordinary temperature may do so when the blood is heated to the
      temperature mentioned. 4. Pus corpuscles, like red blood corpuscles, are worse
      conductors than the serum in which they are suspended. Unlike blood corpuscles,
      they show no preference for NH(4)Cl as compared with NaCl. On the other hand, the
      conductivity of pus is increased by the action of saponin, just as is the case
      with blood, and apparently very much in the same way, that is to say, by an
      action on the corpuscles and not on the serum. The fixing of the pus corpuscles
      by formaldehyde does not hinder this action of saponin.

PMID- 19866974
TI  - ON A COCCIDIUM (KLOSSIELLA MURIS, GEN. ET SPEC. NOV.) PARASITIC IN THE RENAL
      EPITHELIUM OF THE MOUSE.

PMID- 19866973
TI  - SNAKE VENOM IN RELATION TO HAEMOLYSIS, BACTERIOLYSIS, AND TOXICITY.

PMID- 19866975
TI  - A CONTRIBUTION TO THE PHYSIOLOGICAL DIFFERENTIATION OF PNEUMOCOCCUS AND
      STREPTOCOCCUS, AND TO METHODS OF STAINING CAPSULES.
AB  - By morphological examination and with current cultural methods a clear
      differentiation cannot always be made between pneumococci and streptococci. The
      chief differential character usually depended upon is the capsule of the
      pneumococcus. Well-marked capsules, however, may occur on organisms which have
      with reason been classified as streptococci. On the other hand, capsules may not
      he demonstrable on pneumococci by the usual methods, especially when growing on
      artificial culture media. The usual cultural characters and reactions are at best
      not diagnostic, and are subject to variations which may render them useless as
      evidence of specific difference. The experiments recorded in this paper, however,
      afford some evidence that there are well-marked differences between the metabolic
      activities of pneumococci and streptococci, which may prove useful in the
      differentiation of these organisms. These differences in metabolism become
      apparent when the pneumococci and streptococci are cultivated in an alkaline
      serum medium, or in a serum medium to which the carbohydrate, inulin, has been
      added. Pneumococci slowly produce acid in the alkaline serum.

PMID- 19866976
TI  - STUDIES IN HAEMOLYSIS WITH SPECIAL REFERENCE TO THE PROPERTIES OF THE BLOOD AND
      BODY FLUIDS OF HUMAN BEINGS.

PMID- 19866977
TI  - EPITHELIOMA ADAMANTINUM.

PMID- 19866978
TI  - THE BACTERIOLOGY OE BRONCHO- AND LOBULAR PNEUMONIA IN INFANCY.

PMID- 19866979
TI  - A MALIGNANT TERATOMA OF THE PERINEUM.

PMID- 19866980
TI  - DERMATOMYOSITIS, WITH REPORT OF A CASE WHICH PRESENTED A RARE MUSCLE ANOMALY BUT
      ONCE DESCRIBED IN MAN.

PMID- 19866981
TI  - FURTHER OBSERVATIONS ON A PATHOGENIC MOULD FORMERLY DESCRIBED AS A PROTOZOON
      (COCCIDIOIDES IMMITIS, COCCIDIOIDES PYOGENES).
AB  - FROM THE PRECEDING I DERIVE THE FOLLOWING CONCLUSIONS: 1. The disease which
      formerly has been described as a form of protozoon-infection is due to an
      infection with a pathogenic fungus. 2. The infection may primarily be either a
      cutaneous or a pulmonary one. 3. The lesions produced by this fungus fall under
      the general head of infectious granulomata and consist partly in nodules
      resembling altogether those produced by the tubercle bacilli and partly in
      chronic abscesses. 4. The adult forms of the parasite are more apt to produce
      nodules, the sporulating forms abscesses. 5. The fungus is pathogenic for dogs,
      rabbits and guinea-pigs probably other animals also, and in them produces lesions
      very similar to those which we encounter in the human being in this disease. 6.
      Supurative periorchitis in guinea-pigs is not pathognomonic for glanders.

PMID- 19866982
TI  - THE TOXIC EFFECTS OF FORMALDEHYDE AND FORMALIN.
AB  - THE RESULTS OF THIS INVESTIGATION MAY BE SUMMARIZED AS FOLLOWS: 1. The inhalation
      of formaldehyde gas in even small quantities is followed by bronchitis and
      pneumonia. Pneumonia is due to the inhalation of the gas and not to secondary
      infection. 2. Formalin belongs to that rare group of poisons which are capable of
      producing death suddenly when swallowed. 3. The introduction of formalin into the
      stomach is followed by the production of a gastritis which varies greatly in
      character. The duodenum and upper jejunum may also be involved in the
      inflammatory process. 4. Intraperitoneal injections of formalin cause peritonitis
      of a fibrino-haemorrhagic character. A definite reaction is obtained when very
      dilute formalin (1-1000) is employed. In the peritoneal cavity formalin exercises
      a destructive action upon all organs (pancreas, liver, peritoneal fat, Fallopian
      tubes, etc.) with which it comes in contact and causes inflammation in these
      organs. 5. The lethal dose of formalin when injected intraperitoneally into
      guinea pigs is approximately 2 cc. of 1-1000 formalin for each 100 grm. of body
      weight. 6. The injection of formalin into the lungs is followed by pneumonia and
      bronchitis. 7. The inflammation which follows subcutaneous injections of formalin
      is characterized by intense exudation. 8. The injection of formalin into the
      muscles produces myositis. 9. The injection of formalin into the anterior chamber
      of the eye causes the accumulation of an exudate containing leucocytes and
      fibrin. When formalin is dropped into the conjunctival sac iritis follows and may
      be severe enough to destroy the eye. 10. Formalin in whatever way introduced into
      the body is absorbed, and is then capable of producing lesions in the
      parenchymatous organs. 11. Changes in the liver after absorption of formalin
      consist of mild or severe grade of cloudy swelling accompanied by vacuolation of
      the protoplasm, changes in the nuclei and leucocytic infiltration. Focal necrosis
      may result. Similar changes follow the inhalation of formaldehyde. 12. The
      injection of formalin or the inhalation of the vapors of formaldehyde produces
      cloudy swelling of the parenchyma of the kidney. Focal necrosis may result. 13.
      Pneumonia and bronchitis are found in all animals after the injection of
      formalin. 14. The leucocytic infiltration which follows the introduction of
      formalin into an organ has these general characteristics: The eosinophiles are
      the first leucocytes to appear; these are followed by the other polynuclear
      leucocytes; last appear the large and small mononuclear leucocytes. Similar
      phenomena occur in the trachea, bronchi and lungs of animals subjected to
      formaldehyde inhalations. 15. Formalin is, directly or indirectly, chemiotactic
      for leucocytes. The tissues which are not infiltrated with leucocytes after the
      injection of formalin are those which have been so injured by the chemical that
      an inflammatory reaction is impossible. 16. Animals subjected to chronic
      poisoning with formalin administered by intraperitoneal injection develop
      fibrinous peritonitis, associated with marked eosinophilia. The changes in the
      kidneys and liver consist of cloudy swelling, fatty degeneration, focal necrosis
      and leucocytic infiltration.

PMID- 19866983
TI  - BACILLUS MORTIFERUS (NOV. SPEC.).

PMID- 19866984
TI  - THE CHANGES IN THE HEART RATE AND BLOOD "PRESSURES" RESULTING FROM SEVERE
      HAEMORRHAGE AND SUBSEQUENT INFUSION OF SODIUM BICARBONATE.

PMID- 19866985
TI  - ON THE PREPARATION OF SALT-FREE CULTURE MEDIA AND THE GROWTH OF BACTERIA UPON
      THEM.

PMID- 19866986
TI  - "RED-LEG"-AN INFECTIOUS DISEASE OF FROGS.
AB  - The epidemics we have observed, were due to the presence and growth in the frogs
      of Bacillus hydrophilus fuscus. This was proved by recovering the bacillus in
      pure culture from the body fluids of frogs sick or dead of the disease, and the
      inoculation of healthy frogs with an emulsion of the pure culture, and by
      obtaining the same clinical picture and pathological findings as in the original
      diseased frogs; and, finally, by recovering the bacillus in pure culture from
      frogs inoculated and sick or dying as a result of the inoculation. The disease is
      widely distributed throughout North America and Europe, and in this country and
      Canada is known as "red-leg." It has been observed by us chiefly in the warm
      weather of September and October. The disease is characterized by congestion of
      the ventral surfaces of the body, with more or less ulceration in, and
      haemorrhage beneath, the skin, bloating due to serous exudation into the lymph
      sacs, gradual failure to respond to stimuli, which symptoms are followed by coma
      and death, the last being occasionally preceded by tetanic seizures. After death
      haemorrhages into the muscles and degenerative changes in the muscles, spleen,
      liver, and, to a slight degree, in the intestinal tract, are found. The blood
      shows an advanced degree of anaemia and leucocytosis. Predisposing causes of the
      disease are lesions of the skin, which seem to be the usual portal of entry of
      the infection, and lowered resistance from heat and from anaemia. By a series of
      controlled experiments with inoculated frogs we have shown that, while
      temperatures a little above freezing have no harmful effect upon the frogs, they
      completely control all manifestations of the disease in inoculated or diseased
      frogs, if the frogs are left in the cold for a period as long as seven days; and,
      further, that even short periods in the cold chamber will bring about a delay of
      the fatal results in diseased or inoculated frogs. The anaemia so often found in
      apparently healthy frogs seems in many cases to be due to the presence in the
      lungs of the frog of a parasite, the Distomum cylindraceum, which, occurring in
      sufficiently large numbers in an individual frog, is capable of materially
      diminishing the available supply of red corpuscles. Severe laking of the blood,
      the presence of numerous isolated red-cell nuclei, and great diminution in the
      number, or almost total absence of the red cells in the diseased frogs, are in
      proportion to the severity of the infection and due to bacterial action. The
      presence of the haematozoan parasite, the Drepanidium, does not play any part as
      a predisposing or exciting cause of the disease. The ascarid Rhabdomena
      nigrovenosum, although frequently present as a parasite in the lungs of the
      frogs, plays no part in causing or promoting the disease.

PMID- 19866987
TI  - ON THE RATE OF ABSORPTION FROM INTRAMUSCULAR TISSUE.

PMID- 19866988
TI  - THE COLOR REACTIONS OF NAPHTHAQUINONE SODIUM-MONOSULPHONATE AND SOME OF THEIR
      BIOLOGICAL APPLICATIONS.

PMID- 19866989
TI  - A STUDY OF THE CHANGES IN THE BLOOD AND BLOOD-FORMING ORGANS PRODUCED BY
      CYTOTOXIC SERA, WITH SPECIAL REFERENCE TO HAEMOLYMPHOTOXIN.
AB  - (1) The cytotoxins are not specific. (2) The changes occurring after the
      injection of different cytotoxins are similar and do not vary in kind. (3) The
      changes do, however, vary in degree in the following order, the one having the
      most marked effect being placed first, etc.: (a) Haemolymphotoxin, (b)
      Splenotoxin, (c) Lymphotoxin, (d) Endotheliotoxin, (e) Nephrotoxin, (f)
      Hepatotoxin. (4) Nephrotoxin causes the most specific change. (5) The haemolymph
      glands play some important part in the production of eosinophiles. The haemolytic
      action of haemolymphotoxic serum is greater than that of other cytotoxic sera.
      (6) The histological changes which are observed in every case are secondary to
      the haemolytic factor present in all cytotoxic sera.

PMID- 19866990
TI  - THE ARTIFICIAL ANASTOMOSIS BETWEEN THE PORTAL VEIN AND THE VENA CAVA
      INFERIORECK'S FISTULA.

PMID- 19866991
TI  - A SECOND COAGULATION OF THE BLOOD DUE TO A SUBSTANCE THAT IS NOT IDENTICAL WITH
      FlBRINOGEN AND IS COAGULABLE BY SATURATION WITH NEUTRAL OXALATE.

PMID- 19866992
TI  - COMPARATIVE STATISTICS OF ANTITOXIN HORSES. A STUDY OF THE RECORDS OF ONE HUNDRED
      HORSES IMMUNIZED TO DIPHTHERIA TOXIN, WITH COMPOSITE OF CURVES.
AB  - 1. Better results in the production of diphtheria antitoxin can be obtained with
      greater experience in the selection of the most suitable type of horses to be
      used. Young animals are usually to be preferred. Over one-half of all such horses
      can be made to yield 300-unit serum, while a third will yield (5)oo-unit serum.
      2. High-test horses require a shorter time to immunize and will yield a potent
      serum for a longer period than will low-test horses. 3. The period of usefulness
      of an antitoxin horse is short, and on an average endures only a few months. 4. A
      horse having attained a maximal antitoxic height begins to suffer a decline in
      antitoxin, which is usually as rapid as the ascent has been, and is unaffected by
      subsequent injections of diphtheria toxin.

PMID- 19866993
TI  - SOME OBSERVATIONS UPON ENDOTHELIAL SEPARATION IN THE SMALLER ARTERIES AND VEINS.

PMID- 19866994
TI  - A STUDY OF THE PROTECTIVE ACTION OF SNAKE VENOM UPON BLOOD CORPUSCLES.
AB  - Washed blood corpuscles of certain species of animals in a concentration of about
      (5) per cent suspended in salt solution containing above 4 per cent of cobra
      venom undergo changes in their resistance to certain physical and chemical
      agents. They become non-haemolyzable by water, ether, saponin, and quite strong
      solutions of lecithin, provided always that the excess of venom has not been
      entirely removed. On the other hand, certain acids and alkalis, excepting
      ammonia, lake the venomized corpuscles more easily than they lake normal
      corpuscles. Venom solutions of 2 per cent and less exert no protective property
      upon blood corpuscles, but they induce changes in the corpuscles whereby they are
      rendered more easily laked by the same physical and chemical agents.

PMID- 19866995
TI  - A METHOD FOR OBTAINING MASS CULTURES OF BACTERIA FOR INOCULATION AND FOR
      AGGLUTINATION TESTS: : WITH SPECIAL REFERENCE TO PNEUMOCOCCI AND STREPTOCOCCI.

PMID- 19866997
TI  - A METHOD FOR PREPARING A PERMANENT NOCHT'S STAIN (NOCHT-JENNER STAIN).

PMID- 19866996
TI  - SOME QUESTIONS RELATING TO THE VIRULENCE OF MICRO-ORGANISMS WITH PARTICULAR
      REFERENCE TO THEIR IMMUNIZING POWERS.
AB  - The virulent cholera spirillum possesses a greater number of bacteriolytic and
      agglutinable haptophore groups, or these groups are endowed with a greater
      avidity for uni- and amboceptors than the avirulent. The number or the avidity of
      the bacteriolytic receptors possessed by a bacterium is directly proportional to
      its virulence. However, the agglutinable receptors do not follow this law, i.e.,
      the agglutinable haptophore groups are not necessarily present in the same
      proportion as the bactericidal ones. While the energy of growth is a very
      important factor in relation to virulence, other phenomena must also be
      considered. The virulent organism possesses a greater number of toxic haptophore
      groups than the avirulent. The binding power of the free receptors of the
      organisms for bacteriolytic amboceptors in vitro is proportional to the
      bactericidal immunity produced in animals by each, which latter is in turn
      proportional to the virulence of the organisms from which the receptors were
      extracted. The binding power in vitro of the dead micro-organisms of different
      virulence for bacteriolytic amboceptors is not in proportion to their toxicity.
      The bactericidal immunity obtained by means of the inoculation with the dead
      organisms of different virulence, or their extracts obtained by autolytic
      digestion, is proportional to the virulence of the living strains of the bacteria
      employed. With the living organisms, while the bactericidal immunity obtained
      from the inoculation of animals with the virulent organism is greater than that
      produced with the avirulent, such immunity is not in direct proportion to the
      virulence of the bacteria introduced. These conclusions apply to the two strains
      of cholera spirilk employed in the foregoing experiments. Whether they will also
      hold good with other strains of this spirillum or for micro organisms in general,
      must be decided by further experimenta work.

PMID- 19866998
TI  - STUDIES ON THE TOXICITY OF BILE : I. THE EFFECTS OF INTRAVENOUS INJECTIONS OF
      BILE UPON BLOOD PRESSURE.

PMID- 19866999
TI  - ON THE HEXON BASES OF LIVER TISSUE UNDER NORMAL AND CERTAIN PATHOLOGICAL
      CONDITIONS.
AB  - The results above reported lead to the conclusion that while in the degenerating
      cells chemical changes are taking place tending toward a diminution of the hexon
      bases as a whole, they affect the arginin especially. One may picture the process
      either as a partial or as a complete breaking down of certain proteid. material
      more or less rich in hexon bases, leaving behind. proteid matter poorer in bases.
      The meaning of these changes is, however, obscure, and with the limited number of
      known facts bearing upon the subject, it would seem idle even to attempt to
      formulate an hypothesis to explain them. Certain work of other investigators is,
      however, suggestive in this connection. Kossel and Dakin, for instance, as
      illustrated by their work upon the simple proteid body clupein, found that a
      partial destruction of the proteid molecule, involving the arginin group, is
      brought about by a ferment furnished by the animal organism. When subjected to
      the hydrolytic action of a mineral acid, clupein yields arginin in considerable
      abundance. But if the clupein is first acted upon by the ferment arginase found
      in the liver, and then subjected to acid hydrolysis, the yield of arginin is
      appreciably diminished. Among the cleavage products in the latter instance are
      the components of arginin, namely, omithin and urea. It would seem, therefore, as
      if the ferment had loosened the union between the omithin and urea in the arginin
      group, so that upon subsequent hydrolysis a diminution of arginin resulted. In
      the cases studied by me, it may be that the conditions were favorable for some
      such ferment action as that above described, and hence the relatively low yield
      of arginin. No attempt, however, was made to ascertain if omithin were present in
      the urine. Its presence there would seem not wholly unlikely when one considers
      the diminished power of oxidation of the phosphorus-poisoned cell, although
      Thompson has shown that arginin or omithin when administered to a healthy dog as
      food or by hypodermic injection is eliminated for the most part as urea, no
      ornithin being found. There might seem to be a conflict between this view and the
      results recently published by Wohlgemuth, but it must be borne in mind that the
      influences at work causing the breaking down of the proteid molecule are probably
      quite diverse in character. Wohlgemuth has recently shown for the first time that
      a diamino acid may actually find its way into the urine in phosphorus poisoning.
      He found arginin in the urine not only in rabbits poisoned with phosphorus but
      also in a patient suffering from phosphorus poisoning. On the other hand, he was
      unable to find lysin in the urine. This fact is of especial interest in view of
      the evidence set forth in this paper that the arginin base is lost to the proteid
      molecule more rapidly than the lysin base. The correspondence between the
      findings in the liver and in the urine is thus a close one. How much of the
      arginin liberated from the proteid molecule may find its way into the urine is of
      course uncertain. It seems reasonable to suppose that a portion of the base is
      acted upon by the arginase ferment in the manner already described. Of the
      seventeen to eighteen cleavage products of the proteid molecule thus far
      isolated, the hexon bases are among the most stable. One or more of these bases
      have been found in practically all proteid matter thus far investigated; in fact
      arginin is so uniformly present that Kossel has made the suggestion that it is
      the kernel of the proteid molecule. At all events, the question may be asked,
      whether, if the influences at work in the altered liver tissue were of a general
      character causing a diminution of the hexon bases, the monoamino acid groups
      would not suffer even a greater diminution; and since the pathological condition
      is undoubtedly associated with impaired oxidation, their presence should not be
      expected in the urine. As a matter of fact, Ignatowski found considerable
      quantities of monoamino acids in the urine of patients suffering from gout,
      pneumonia, and leukaemia, though under normal conditions no monoamino acids were
      found in the urine, indeed, not even after the subcutaneous injection of
      glycokoll. Furthermore, the loosening of the amino acids from the proteid
      molecule is suggested by the fact that Taylor found such acids in the liver of a
      patient who died from a hepatic disease of obscure etiology, but which he was
      inclined to attribute to chloroform poisoning. Taylor found not only leucin and
      tyrosin in the liver, but also arginin, a fact not without interest in view of
      the diminished arginin content found in the livers of the chloroformed dogs after
      acid hydrolysis. Moreover, the falling off of the hexon bases under the
      conditions studied seems quite in accordance with some results recently reported
      by Levene. He has shown that certain cleavage products obtained by the action of
      mineral acids upon self-digested pancreas, spleen, and liver, are much diminished
      when compared with the products obtained from the fresh glands. The lysin and
      arginin of the digested liver, for example, showed a diminution of over 50 per
      cent. It is now well established that in course of the process of aseptic
      autolysis, the proteids of the liver cell undergo decomposition into simpler
      substances, and Jacoby showed that during life autolysis may go on in portions of
      the liver in which the circulation has been hindered. But of greater significance
      still in this connection, is the observation made by Jacoby on the autolytic
      changes in the liver during phosphorus poisoning. He found that when the normal
      liver substance is permitted to autolyse the solution of the liver substance is a
      slow one. On the other hand, under similar conditions the liver of a phosphorus
      poisoned animal undergoes rapid and almost complete solution. The difference in
      the behavior of the normal and damaged liver points to an increase of normal
      ferment action in the case of the poisoned organ. It thus seems reasonable to
      suppose that in phosphorus poisoning we have during life an exaggerated breaking
      down of the proteid molecule associated with an over-action of certain ferments,
      and among them probably arginase. The pathological process in the liver during
      life may, therefore, be thought of as proceeding in the same general direction as
      the process of post-morten autolytic decomposition. By means of further studies
      along lines indicated in this paper, it should be possible to gain a deeper
      insight into numerous pathological processes. The changes in amyloid degeneration
      are among those which promise to be better understood through the application of
      the new methods of chemical analysis. Moreover, it cannot be doubted that
      pharmacology as well as toxicology has much to gain from a study of what happens
      to the proteid molecule under the influence of poisons.

PMID- 19867000
TI  - THE CONSTRUCTION OF A THERMOSTAT-ROOM.

PMID- 19867001
TI  - ENZYMES AND ANTI-ENZYMES OF INFLAMMATORY EXUDATES.
AB  - The serum of an inflammatory exudate has the power of inhibiting the action of
      proteolytic ferments contained in the leucocytes. This anti-enzymotic power is
      possessed by the blood serum from which it doubtless passes into the exudate. In
      the later stages of inflammation there is some diminution of this anti-enzymotic
      action. The anti-body contained in the serum is destroyed by a temperature of 75
      degrees C. The proteolytic ferments of the leucocytes act both in an acid and in
      an alkaline medium but are most efficient in the latter. The anti-enzymotic
      action of the serum is favored by an alkaline reaction, but is completely lost in
      an acid medium.

PMID- 19867002
TI  - A STUDY OF THE BACTERIOLOGY OF PERTUSSIS, WITH SPECIAL REFERENCE TO THE
      AGGLUTINATION OF THE PATIENT'S BLOOD.

PMID- 19867003
TI  - ON THE PRESENCE OF CERTAIN BODIES IN THE SKIN AND BLISTER FLUID FROM SCARLET
      FEVER AND MEASLES.
AB  - In sections of control and normal skin, the nuclei of the epithelial cells were
      often indented by the cell protoplasm, giving them an appearance similar to those
      indented by Mallory's bodies. It would seem that if these bodies of Mallory's
      were protozoa they would have been found in the sections from both the living and
      the dead skin of scarlet-fever and measles, as they were present in the blister
      fluid. Their absence is certainly more suggestive of a degeneration than of a
      protozoon. This view is also borne out by the fact that they were not found
      immediately after death, but were present in another specimen from the same case
      removed twenty-four hours later. It would seem probable also that the bodies
      found in the blister fluid were the products of degeneration and cytolytic
      activity, because they were found in the antitoxin rashes as well as in the cases
      of scarlet-fever and measles. The histological changes in the skin of these two
      diseases leads us to expect the presence of cytolytic products both in the
      blister fluid and in the sections. It certainly cannot be stated that none of
      these bodies is a protozoon, but it can be positively stated that a great
      majority of them arise from degenerating cells; and in many cases, I think, it is
      not possible to differentiate a degeneration from a protozoon by the study of its
      morphology and staining reactions. The bodies present in blister fluid resemble
      very closely those granular bodies found in blood under certain conditions, and
      seen in vaccine lymph and in emulsions of tissues and in exudates. I think,
      therefore, that they are for the most part, if not wholly, products of
      degenerating tissue cells and of leucocytes, and within certain limits specific
      to scarlet-fever and measles.

PMID- 19867004
TI  - CONCERNING THE POSSIBILITY OF AN ANTIBODY FOR THE TETANOPHILE RECEPTOR OF
      ERYTHROCYTES: A RECEPTOR STUDY.
AB  - The treatment of washed erythrocytes of the guinea-pig by a heated immune
      hemolytic serum derived from the rabbit, and of washed erythrocytes of the sheep
      by a similar serum derived from the goat, renders the erythrocytes more or less
      resistant to the subsequent action of tetanolysin. If all the serum is removed
      from corpuscles treated in this manner, it can be determined that some of the
      protection is due to the agglutination of the cells. A certain amount of the
      protection afforded by agglutination is referable to the physical barrier which
      the agglutinated mass of cells offers to the uniform distribution and diffusion
      of the tetanolysin. It is probable that none of the protection obtained is due to
      the mere union of agglutinin or of hemolytic amboceptors with their respective
      cell-receptors; such union would appear to leave the tetanophile receptors still
      unoccupied. If a residuum of serum is left with the corpuscles which have been
      treated as indicated, the added protection which is acquired against the
      subsequent action of tetanolysin may reasonably be referred to antitoxin which is
      present in the residual serum. The possibility of the dissociation of a union
      between the tetanophile receptor and its antibody, occasioned by the dilution
      incident to washing away the serum, may not be entirely ignored, but has not been
      susceptible to determination. The same may be said of the possibility that
      tetanolysin, having a stronger affinity for the tetanophile receptor than has the
      antibody, is able to displace the latter from its union with the receptor. Hence
      treating corpuscles with the immune serums does not allow one to determine the
      presence or absence of an antibody for the tetanophile receptor, the experiments
      being formulated on the supposition that such an antibody would unite with the
      tetanophile receptors and thereby prevent subsequent binding of tetanolysin.

PMID- 19867005
TI  - A COMPARATIVE STUDY OF DYSENTERY AND DYSENTERY-LIKE ORGANISMS.
AB  - The group of dysentery organisms is a large and. varied one. It may be divided,
      as is well known, into two main sub-groups, the "Shiga-Kruse" and the "mannit
      fermenters," which are of equal importance and entirely distinct. If we take
      decided differences in agglutination, as determined by absorptions, as a
      criterion of specificity, the latter group includes at least four distinct
      species with a number of sub-varieties and transition forms. Two of the above
      species are found among organisms which split either dextrose, mannit, and
      saccharose or in addition maltose. The other two species are represented by the
      bacillus "Y" of Hiss and Russell and the "Flexner-Manila" bacillus. If we adopt
      Ford's proposal, that a new species should be made for each culture showing a
      constant cultural or agglutinative difference, the number would increase
      considerably. At the best, however, classification of bacteria is at present very
      artificial. Although so many types appear among the " mannit-fermenters," there
      is no reason why they should not all be included in the dysentery group of
      bacilli, provided the reaction in litmus milk be typical. This cultural test, as
      Duval has emphasized, is the most constant one which we have at present, but it
      should extend over several weeks in order to exclude lactose fermenters. In
      contradistinction to the heterogeneity of the "mannit-fermenters," the
      homogeneity of the "Shiga-Kruse" type stands in marked contrast. Every culture of
      the latter which. was tested (about twenty in all) reacted in all media and
      agglutinated with all the various sera exactly alike. One is tempted to explain
      this diversity of the "mannit-fermenters" by accepting the suggestion of Flexner,
      that they may be occasional, if not constant, inhabitants of the normal
      intestine. Certainly Duval has isolated the "mannit-fermenters" from the mildest
      cases of diarrhoea, to say nothing of the two apparently normal infants from
      which he also obtained them. Furthermore, the agglutinins for the mannit group in
      normal blood might be accounted for on this hypothesis, as well as the many
      differences in fermentation and agglutination. For, as has been well said by
      Smith and Reagh, one " should keep in mind the various adaptations in the
      intestine-it may be to the food remains in the large intestine, to the mucus on
      the surface of the epithelium, to the contents of the tubules and the larger
      flask-shaped glands, and further, with this progressive adaptation are associated
      modifications of biological characters which most likely involve agglutinative
      capacities as well." The fact that dysentery bacilli have not been isolated
      frequently from the normal intestine might be explained by their habitat being
      possibly within the mucus tubules and their number few under normal condition,
      for it is well known that they are most frequently found in association with
      mucus. When abnormal conditions, however, arise and the production of mucus
      increases, these organisms would possibly multiply in number pari passu and find
      themselves in a favorable position to attack any slight injury which might occur
      in the wall of the intestine. The "Shiga-Kruse," or Group I, type, on the other
      hand, seems to present the characters of a true parasite. Only an insignificant
      amount of agglutinin is present for it in normal human blood and that of
      laboratory animals, according to most authorities; it agglutinates alike in
      various immune sera; it has a very marked toxicity for laboratory animals; it has
      never been isolated from the normal human intestine, although an organism in some
      respects like it has been described by Ford as being an inhabitant of the normal
      intestine; it produces no indol; it splits only the monosaccharids, through which
      it falls in line with the conclusion of Smith and Reagh, that the less a bacillus
      acts on sugars the more pronounced is its parasitic character. Whether or not it
      ever invades the blood in numbers is a question yet to be decided.

PMID- 19867006
TI  - A COMPARATIVE STUDY OF DYSENTERY AND DYSENTERY-LIKE ORGANISMS.

PMID- 19867007
TI  - A STUDY OF PNEUMOCOCCI: A COMPARISON BETWEEN THE PNEUMOCOCCI FOUND IN THE THROAT
      SECRETIONS OF HEALTHY PERSONS LIVING IN BOTH CITY AND COUNTRY AND THOSE OBTAINED
      FROM PNEUMONIC EXUDATES AND DISEASED MUCOUS MEMBRANES.
AB  - 1. Typical pneumococci were present dunng the winter months in the throat
      secretions of a large percentage of healthy individuals in city and country. 2. A
      higher percentage of atypical strains of pneumococci have been obtained from
      healthy persons than from those suffering from pneumonia. In the latter cases the
      atypical strains may have been overlooked, because of the larger number of
      typical pneumococci present. Many of the atypical strains seem to be closely
      related to the streptococci. 3. The so-called Streptococcus mucosus Schottmuller,
      which has hitherto been classed with the distinct streptococci, is placed as a
      definite variety among the pneumococci, and it is recommended that the name be
      changed to Streptococcus lanceolatus, var. mucosus. 4. A lower percentage of
      strains of pneumococci virulent for rabbits in the doses used has been obtained
      from normal cases by rabbit inoculations of mass cultures than from cases of
      pneumonia by the same method. 5. Since the virulence of pneumococci may be
      rapidly increased for a susceptible species of experimental animal by successive
      passage, and since pneumococci obtained from most pneumonias are more virulent
      for experimental animals than are those obtained from healthy individuals,
      therefore the virulence of pneumococci from cases of human infection is probably
      increased for human beings; hence cases of pneumonia should be considered to a
      certain degree as contagious and, since the virulence of the pneumococcus may be
      quickly increased and since the organism is very prevalent in normal sputum, all
      possible measures should be taken to restrict public expectoration. 6. By
      repeated inoculations into sheep of a pneumococcus strain, a specific protective
      power of this serum for mice is developed against the homologous strain and
      against certain other strains, one morphological variety (Streptococcus
      lanceolatus, var.mucosus) being thus clearly differentiated from other strains.
      7. Coincident with this production of protective power, a slight specific
      increase of the sheep serum in phagocytic power in vitro has been observed with
      some strains of pneumococci, all strains of Streptococcus lanceolatus, var.
      mucosus, acting similarly with the serum produced by the inoculation of one
      strain; the strains of some other varieties, however, have shown no definite
      relationship between the phagocytic power and the protective power of the serum.

PMID- 19867008
TI  - THE APPLICATION OF THE REACTION OF AGGLUTINATION TO THE PNEUMOCOCCUS.
AB  - Owing to unavoidable circumstances only a limited amount of time was available
      for the work on agglutination. The foregoing report is therefore preliminary only
      and the following conclusions are provisionally offered: I. Pneumococci by reason
      of their agglutinating properties exhibit a tendency to separate into numerous
      groups similar to streptococci. II. Pneumococcus mucosus forms a distinct and
      consistent variety. The production by it of common agglutinins for some
      pneumococci and the resistance of the agglutinins produced by it to absorption by
      the streptococcus indicate a nearer relation to the former than to the latter
      organism. III. The agglutinating substances in the serum of immunized animals
      were demonstrated by absorption tests to consist of specific and group
      agglutinins in cases where the agglutinins were sufficiently developed to make
      use of this method. IV. The pneumococci seem to show marked differences in their
      ability to undergo agglutination. V. There was considerable uniformity of
      reaction of the various strains in low dilutions, but this uniformity is not
      continued as the animal becomes more highly immunized. VI. At present it is not
      possible to establish a definite relation between the agglutination reaction and
      the other characteristics of the pneumococcus excepting in the case of the
      Pneumococcus mucosus.

PMID- 19867009
TI  - A COMPARATIVE STUDY OF PNEUMOCOCCI AND STREPTOCOCCI FROM THE MOUTHS OF HEALTHY
      INDIVIDUALS AND FROM PATHOLOGICAL CONDITIONS.

PMID- 19867011
TI  - STUDIES ON THE PNEUMOCOCCUS.

PMID- 19867010
TI  - A STUDY OF PNEUMOCOCCI AND ALLIED ORGANISMS IN HUMAN MOUTHS AND LUNGS AFTER
      DEATH.
AB  - THE FOLLOWING CONCLUSIONS MAY BE DRAWN, BASED UPON THE RESULT OF OUR RESEARCHES:
      1. Organisms of the pneumococcus or streptococcus group are present in the lungs
      of practically all cases, whether normal or showing a variety of lesions;
      strictly speaking, they were found by us in forty out of forty-two cases, or in
      95% of our series. 2. The pneumococci and the streptococci were obtained in
      practically similar percentages-that is, in 50 % of the cases. 3. Pneumococci
      were not obtained more frequently in the small series of patients exposed for
      some time to hospital atmosphere; our tables show the contrary to obtain. The
      number of cases examined were, however, insufficient, and the findings may thus
      be accidental, and hence of no value. 4. Test micro-organisms, namely, small
      portions-half a drachm or less-of B. prodigiosus, introduced into the human mouth
      after death, were conveyed to and recovered from the lungs by culture in a little
      over half of the cases in which this experiment was tried. The test micro
      organisms are, we believe, conveyed to the lungs with the fluid which collects in
      mouths of persons after death, and which in many cases collects just before
      death. The numerous manipulations entailed in the removal of the body from the
      wards to the morgue greatly facilitate the entrance of any fluid from the pharynx
      and buccal cavity into the lungs. It follows logically, from the results obtained
      in this experiment, that the cultural findings after death are no guide to the
      bacterial contents of the lungs during life, and that any deductions made from
      such findings are unreliable and deceptive. Granted that our explanation be
      correct, there is every reason to believe that any of the micro-organisms present
      in the mouths and pharynx and in many cases in the stomach contents may enter the
      lungs and, if the conditions be suitable, increase in numbers, during the time
      between death and the examination of the lungs. There exists, perhaps, more
      frequently than has hitherto been suspected, a series of diplococci, intermediate
      between the typical pneumococci and streptococci. The diplococci of this type
      have been found in forty (40) per cent. of our cases. The differential diagnosis
      of these atypical diplococci from the pneumococci and streptococci is a difficult
      one, depending, as it does, upon general cultural characteristics. No single
      character, such as the presence of capsules or the fermentation of inulin,
      virulence, etc., has been found to be a certain criterion. The few agglutinative
      reactions we have made seem to show that these intermediate diplococci, those of
      Groups II, III, and IV, have no or only slight agglutinative affinities to the
      typical pneumococcus. Further tests must, however, be made with the various
      methods at our disposal before this statement can be accepted as final. These
      diplococci are of interest from the fact that they have been found in the blood
      during life, and in the pial exudate of cases of meningitis, endocarditis, etc.
      6. Our studies have thrown no light whatever upon the conditions which determine
      the onset of lobar pneumonia in apparently healthy persons. Moreover, we have
      been unable to draw conclusions as to the presence of pneumococci in the lungs
      during life, or as to the channels by which they gain access thereto.

PMID- 19867012
TI  - STUDIES OF THE PNEUMOCOCCUS AND ALLIED ORGANISMS WITH REFERENCE TO THEIR
      OCCURRENCE IN THE HUMAN MOUTH.
AB  - 1. In the course of experiments for obtaining pneumococci from the oral
      secretions of human individuals, the "plate method" described in this paper was
      found to be the most reliable method for isolating pneumococci. 2. An alkaline
      two-per-cent, glucose-serum-agar was regarded as the most favorable medium for
      the rapid development of colonies of the pneumococcus. 3. The morphological
      identification of the pneumococcus was made by means of a special capsule-stain.
      The recognition of the organism was accomplished with precision and reliability
      when present in the blood and exudate of test animals, and upon the various
      culture media employed. 4. Pure cultures of pneumococci could by the methods
      described be obtained within forty-eight hours for inoculation into animals for
      tests of virulence. 5. Normal persons often harbor the pneumococcus in their
      mouths. Of the seventy-eight cases examined, thirty-nine showed the presence of
      the pneumococcus. 6. In a second and larger series of studies on so-called normal
      cases by means of cultures made from the throat on Loeffler's medium, the
      organism was detected seventy-one times in 204 examinations, or in 348%. In 145
      cases the Streptococcus mucosus capsulatus occurred eight times (5.5%), and the
      Friedlander bacillus twenty-one times (14.5%). 7. Certain individuals may acquire
      the pneumococcus in their mouths in the hospital wards, and may continue to
      harbor it for a considerable period of time. 8. The pneumococcus may persist for
      days or weeks in the mouths of patients who have recovered from pneumonia. 9.
      From a study of patients in the hospital wards, certain conclusionsin regard to
      communicability were drawn. "Normal" individuals, in whose mouths the
      pneumococcus is repeatedly found to be absent, may acquire the organism by
      association with pneumonia or "positive normal" cases. The handker-chiefsand
      dishes of pneumonia and "positive normal" cases are to be regarded as some of the
      means of transference of the organismfrom person to person. The lips of drinking
      cups and the sputum or saliva in sputum cups were found to contain living and
      virulent pneumococci. 10. Certain characteristic morphological types of the
      pneumococcuswere regularly met with in this study. These include the following:
      (1) the typical, (2) the small, (3) the large, (4) the bacillary, and (5) the
      streptococcus type of the pneumococcus. 11. Pneumococci in the mouths of normal
      individuals possess the morphological and cultural properties which are
      characteristic of the same organisms when isolated from other sources. 12. All
      pneumococci possess the power of fermenting inulin with the formation of acid,
      even if not in all generations. But this holds true only when the inulin serum
      water medium as modified by the writer is used. 13. A certain configuration of
      the colonies, designated by the term "ring-form," when present is diagnostic of
      the pneumococcus. 14. The percentage of virulent pneumococci present in the
      mouths of normal persons was 79; in cases of pneumonia, 77. 15. Pneumococci of
      the large mucoid type, and giving large mucoid colonies, should be distinguished
      from the Streptococcus mucosus capsulatus. 16. There are doubtful diplococci of
      atypical morphology which can be grouped neither with the pneumococci nor with
      the streptococci, although they possess many features in common with both. 17.
      The Streptococcus mucosus capsulatus belongs to a group which is related to, but
      distinct from, the pneumococcus. 18. Morphological characters and animal tests
      are of greatest value in the identification of the pneumococcus. By the
      employment of suitable culture media it is possible, in most instances,to
      recognize the pneumococcus by its morphology alone. The chief cultural tests are
      the following: the manner of growth upon the serum-glucose-agar, and the modified
      inulin-serum water, and the appearance of the "ring-type" of colony. 19. All
      pneumococci, irrespective of their source, were agglutinatedby means of
      pneumococcus immune serum. 20. An immune pneumococcus serum was found capable of
      agglutinating various pyogenic streptococci, certain atypical organisms, and
      several strains of the Streptococcus mucosus capsulatus. 21. The serum of
      pneumonia patients varied in its power to agglutinate different pneumococci. Some
      strains were agglutinated, others not. 22. The sera of normal individuals and of
      normal rabbits possess no agglutinating power for pneumococci, the atypical
      organisms, certain streptococci, and the Streptococcus mucosus capsulatus.

PMID- 19867013
TI  - A COMPARATIVE STUDY OF PNEUMOCOCCI AND ALLIED ORGANISMS : THE REPORT FROM THE
      CENTRAL LABORATORY TO THE MEDICAL COMMISSION FOR THE INVESTIGATION OF ACUTE
      RESPIRATORY DISEASES OF THE DEPARTMENT OF HEALTH OF THE CITY OF NEW YORK.
AB  - The work carried on under the auspices of the Medical Commission for the
      Investigation of Acute Respiratory Diseases, at the Bacteriological Laboratory of
      the College of Physicians and Surgeons, Columbia University, has consisted
      principally of a comparative study of the morphology, growth characters,
      fermentative activities, and agglutination reactions of pneumococci and allied
      organisms isolated by ourselves and the various workers under the Commission.
      These organisms were from two chief sources: (a) from the mouth and naso-pharynx
      of supposedly normal persons and persons suffering from minor inflammations of
      the naso-pharynx, and (b) from definitely pathologic sources, such as pneumonic
      sputum, pneumonic lungs, empyaema, the circulating blood of pneumonia patients,
      septicaemias, meningitis, and various minor lesions, usually due to infection
      with pneumococci. One of the principal objects of the study was to make a careful
      comparison, in the light of the most recent knowledge of the biology of the
      pneumococcus and by the aid of the latest biological and technical methods, of
      the series of organisms from these two sources, and thus to determine definitely
      the true nature of pneumococcus-like organisms occurring in the mouths of normal
      persons. The second and equally important object, ultimately dependent, however,
      upon the solution of the first, was the determination of the frequency of
      occurrence of typical pneumococci in the mouths of healthy individuals. The
      investigations detailed in the present paper have dealt chiefly with the first
      problem and incidentally with the second, and lead to the following conclusions:
      (a) That organisms, not to be distinguished by morphological characters or by any
      physiological peculiarities from true pneumococci derived from pathologic
      sources, occur with frequency in the mouths of healthy persons and those
      suffering from slight inflammations of the naso pharynx, and that the only
      permissible and legitimate conclusion is that these organisms are true
      pneumococci. (b) That there are other organisms in normal mouths and from
      pathologic sources that morphologically or by staining reactions are not
      definitely to be distinguished from pneumococci, and can only be recognized by a
      careful study of their fermentative activities and agglutination reactions. These
      organisms are non-inulin fermenters. (c) That the organism known as Streptococcus
      mucosus is at times found in cultivations from the mouths of apparently healthy
      individuals, and that, although it shows certain peculiarities distinguishing it
      from the typical pneumococcus, it is probably very closely related to, and a
      variety of, this species.

PMID- 19867014
TI  - THE VIABILITY OF THE PNEUMOCOCCUS AFTER DRYING: A STUDY OF ONE OF THE FACTORS IN
      PNEUMONIC INFECTION.
AB  - I. In moist sputum kept in the dark at room temperatures the average life of the
      pneumococcus is eleven days, though considerable variations may be noted in
      different specimens of sputum. In the same sputum kept at o degrees C. the
      average life of the organism is thirty-five days. In sputum kept at room
      temperature and in a strong light the pneumococcus lives less than five days. II.
      In dried sputum (a) in the dark the pneumococcus lives on an average thirty-five
      days; (b) in diffuse light, thirty days; (c) in sunlight, less than four hours.
      III. In powdered sputum even when kept in the dark the death of the pneumococcus
      takes place in from one to four hours. When exposed to sunlight death occurs
      within an hour. IV. No important differences were noted in the life of the
      pneumococcus when dried on glass, tin, or wood. On cloth the life was usually
      slightly longer than on non-absorbing surfaces. V. Sprayed sputum particles
      remain in suspension for twenty-four hours, but all masses of a size sufficient
      to contain bacteria settle at a rate of about 40 cm. per hour. VI. When sputum
      containing pneumococci is sprayed the organisms rarely survive for more than an
      hour, and often die in less time. The substance upon which the particles fall
      makes but little difference in the life of the organism. On cloth a slight
      prolongation is occasionally noted, due perhaps to the slow drying. VII. The
      mucus of the sputum exerts a destructive action on the pneumococcus. VIII.
      Exposure of bacterial spray to sunlight while in suspension results in the
      destruction of the pneumococcus within half an hour.

PMID- 19867015
TI  - A NOTE UPON THE GROWTH OF PNEUMOCOCCI AND STREPTOCOCCI IN BLOOD SERUM.

PMID- 19867017
TI  - ON THE PHYSIOLOGY OF HEART-BLOCK IN MAMMALS, WITH ESPECIAL REFERENCE TO THE
      CAUSATION OF STOKES-ADAMS DISEASE.

PMID- 19867016
TI  - STUDIES UPON CALCAREOUS DEGENERATION : I. THE PROCESS OF PATHOLOGICAL
      CALCIFICATION.
AB  - IT WILL BE SEEN FROM THE ABOVE THAT WE HAVE STUDIED THE CONDITIONS ASSOCIATED
      WITH THE DEPOSIT OF CALCAREOUS SALTS: (I) in connection with normal and
      pathological ossification, and (2) in pathological calcification as exhibited in
      (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions;
      (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we
      have induced experimentally deposits of calcareous salts in the lower animals:
      (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and
      (c) in connection with fat necrosis. I. We have found that bone formation and
      pathological calcareous infiltration are wholly distinct processes. In the former
      there is no evidence of associated fatty change, and the cells associated with
      the process of deposition of calcium are functionally active. In the latter there
      is an antecedent fatty change in the affected areas, and the cells involved
      present constant evidences of degeneration. The view that would seem to account
      best for the changes observed in the latter case is that with lowered vitality
      the cells are unable to utilize the products brought to them by the blood, or
      which they continue to absorb, so that the normal series of decompositions
      associated with their metabolism fails to take place and hence they interact
      among themselves in the cytoplasm with the result that insoluble compounds
      replace soluble ones. II. Besides the fact that calcification is always preceded
      by fatty change within the cells, another fact should be emphasized. namely: that
      combination of the fats present with calcium salts to form calcium soaps tends to
      occur. The stages immediately preceding these are difficult to follow with
      anything approaching certainty, perhaps because the earlier stages vary under
      different conditions. In fat necrosis, for instance, the cells affected are
      normally storehouses for neutral fats, and as long as they remain healthy neutral
      fats alone are present in them. When they are subjected to the action of the
      pancreatic juice with its fat-splitting ferment the cells are killed and
      coincidently the neutral fats are decomposed, fatty acids being deposited. The
      fatty acids now slowly combine with the calcium salts. In degenerating lipomata
      the process would seem to be similar. But in other cases the cells are not
      obviously fat-containing in the normal state; nevertheless prior to calcification
      they undergo so-called fatty degeneration, which is really a form of cell
      degeneration accompanied by fat infiltration. As regards the source of the cell
      fats in general we may safely accept: 1. That fats are transported in the blood
      as diffusible soaps. 2. That taken up by the cells these soaps may either- (a) Be
      reconverted into neutral fats and become stored in the cytoplasm as such, or (b)
      undergo assimilation proper, becoming part and parcel of the cell substance, in
      which case they are not recognizable by the ordinary microchemical tests. 3. If
      these two possibilities be accepted it follows that the appearance of fats and
      soaps in the degenerating cell may be due to either- (a) Absorption or
      infiltration of soaps from the surrounding medium, the degenerating cell
      retaining the power of splitting off the fat but being unable to utilize this in
      metabolism. (b) Cytoplasmic disintegration with dissociation of the soap-albumen
      combination or, more broadly, liberation of the fats from their combination with
      the cytoplasm. The appearances seen in the cells of atheromatous areas indicate
      that the first of these does occur. III. In areas undergoing calcareous
      infiltration we have demonstrated. the presence of soaps, and this often in such
      quantities that they can be isolated and estimated by gross chemical methods. By
      microchemical methods also we have been able to show that after removing all the
      neutral fats and fatty acids by petroleum ether there remains behind a substance
      giving with Sudan III the reaction we associate with the presence of soap. And
      experimentally we have produced these soaps within the organism, more
      particularly by placing capsules containing fats and fatty acids within the
      tissues and after several days finding that the capsules contain calcium soaps
      and possess a calcium content far in excess of that of the normal blood and
      lymph. IV. While these are the facts, certain of the details of this reaction
      demand elucidation. The existence of sodium and it may be potassium soaps in the
      degenerated cells is comprehensible if we accept that these are present in the
      circulating lymph and simply undergoing absorption. But even then, as these are
      diffusible substances how is it to be explained that they become stored up in
      these particular areas? We have found that, as a matter of fact, in regions which
      give the reaction for soaps, but which give no reaction for calcium (which
      therefore presumably contain at most amounts of the insoluble calcium soap too
      small to need consideration, the ordinary solvents for potassium and sodium soaps
      do not forthwith remove the stainable material; they are relatively insoluble.
      The reason for this insolubility is suggested by the observations made in the
      test tube, that soap solutions mixed with solutions of white of egg or blood
      serum form a precipitate of combined soap and albumen, which likewise is
      insoluble in water and alcohol. The indications are therefore that in cells
      undergoing degeneration, with degeneration of the cytoplasm, certain albuminous
      molecules unite with the soaps present to form relatively insoluble soap
      albuminate. V. With regard to calcium soaps, these are also present and in
      certain stages appear to be the dominating form in the affected tissues. Two
      questions suggest themselves, viz.: what is the source of calcium, and what is
      the process by which they become formed? As to the source, the amount present in
      well-marked calcification is far in excess of the normal calcium contents of the
      affected tissue. If in the kidneys of experimental calcification three hundred
      times as much calcium may be present as in the normal kidney (von Kossa), the
      calcium must be conveyed to the part by the blood and lymph, and that this is so
      is demonstrated, as we have pointed out, by the distribution of the infiltration
      in solid organs, that like ovarian fibroids have undergone necrosis, in which the
      earliest deposits are superficial. As to the process, there are three
      possibilities: 1. That sodium and potassium soaps and soap albuminates are first
      formed and that interaction occurs between them and the diffused calcium salts
      from the lymph, the less soluble-calcium replacing the sodium and potassium. 2.
      That under certain conditions the calcium salts act directly on the neutral fats
      present in the degenerating cells. 3. That the neutral fats are first broken down
      into fatty acids and that these react with the calcium salts to form the soaps.
      We are assured that the first process occurs and that because in the boundary
      zone of areas of calcification we can detect soapy particles devoid of calcium,
      identical in position and arrangement with the particles more deeply placed which
      give the calcium reactions. But this is not the only reaction. In case of fat
      necrosis we see clearly that the third process is in evidence. And we are far
      from being convinced that the second does not also obtain. We have been impressed
      by the large accumulation of neutral fats in the cells in cases of early atheroma
      and the absence at any stage of the process of recognizable fatty acid. While
      soaps, it is true, are compounds of fatty acids with alkalies, it is recognized
      in ordinary domestic life that they can be formed by the direct action of strong
      lye upon ordinary fats, and this even in the cold. It is quite possible therefore
      that there occurs a similar direct process in the organism. The point is worth
      noting, however, that this does not occur in healthy cells the seat of fatty
      infiltration. We therefore leave this an open question, only laying down that, as
      indicated by the hyalin albuminous matrix left when calcium salts are dissolved
      out of an area of calcification, there must exist a calcium soap- or fat
      albuminate similar to the potassium and sodium soap-albuminates already mentioned
      such an albuminate as we can form with calcium soaps in the test tube. VI. In old
      areas of calcification soaps are largely if not entirely wanting, although these
      are to be detected at the periphery, when the process is still advancing. The
      reactions given by these older areas are almost entirely those of calcium
      phosphate, though some calcium carbonate is at times to be made out. This seems
      surely to indicate that the final stage in calcification is an interaction
      between the calcium soap-albuminates and substances containing phosphoric and
      carbonic acids. Such substances, it is needless to say, are present in
      considerable amounts in the lymph and blood. We must conclude that the acid
      sodium phosphates of the lymph act on the calcium soap, the highly insoluble
      calcium phosphates being formed (plus the albuminous moiety of the original
      compound) and diffusible sodium soap being liberated, while similarly alkaline
      carbonates form calcium carbonate and liberate sodium and potassium soaps.
      Calcium phosphate and calcium carbonate thus become the insoluble earthy salts of
      old crystalline areas of calcification. VII. As already stated very little soap
      is to be found in these old areas. It is possibly worth suggestion that the soaps
      liberated in this last reaction, as they diffuse out, again react with diffusible
      calcium salts and form calcium soaps which once more react with the alkaline
      salts to produce the phosphates and carbonates; that, in short, they have a
      katalytic action. (ABSTRACT TRUNCATED)

PMID- 19867018
TI  - THE ACTION OF GLYCERIN ON BACTERIA IN THE PRESENCE OF CELL EXUDATES.

PMID- 19867019
TI  - CYTOTOXIC SERUM PRODUCED BY THE INJECTION OF NUCLEOPROTEIDS.

PMID- 19867020
TI  - A CONTRIBUTION TO THE TECHNIQUE OF MAKING THE ECK FISTULA.

PMID- 19867021
TI  - THE PRESENCE IN THE BONE-MARROW OF ENZYMES RESEMBLING THOSE OF LEUCOCYTES.

PMID- 19867022
TI  - THE EFFECT OF EOSIN UPON TETANUS TOXIN AND UPON TETANUS IN RATS AND GUINEA-PIGS.

PMID- 19867023
TI  - A FURTHER CONTRIBUTION TO THE KNOWLEDGE OF MULTIPLE NON-INFLAMMATORY NECROSIS OF
      THE LIVER WITH JAUNDICE (HEPAR NECROTICUM CUM ICTERO), AND TO THE KNOWLEDGE OF
      CELL DEGENERATION AND CYTOLYSIS IN GENERAL.

PMID- 19867024
TI  - NEUROMA EMBRYONALE OF THE CHOROID PLEXUS OF THE CAT.

PMID- 19867026
TI  - THE CONSTITUENT OF THE BILE CAUSING PANCREATITIS AND THE EFFECT OF COLLOIDS UPON
      ITS ACTION.

PMID- 19867025
TI  - STUDIES ON THE TOXICITY OF BILE : II. THE TOXIC EFFECTS OF BILE UPON THE CENTRAL
      NERVOUS SYSTEM AND THE ELIMINATION OF STRYCHNINE THROUGH THE BILE IN
      NEPHRECTOMIZED ANIMALS.

PMID- 19867027
TI  - ON THE CARBOHYDRATE GROUP IN THE NUCLEOPROTEID OF THE SPLEEN.

PMID- 19867028
TI  - ON A CERTAIN CRYSTALLINE BODY OBTAINED ON THE PROLONGED DIGESTION OF GELATINE.

PMID- 19867030
TI  - THE EFFECT OF CHANGES IN TEMPERATURE UPON THE VISCOSITY OF THE "LIVING" BLOOD.

PMID- 19867029
TI  - GASTRIC ULCERS IN RABBITS FOLLOWING RESECTION OF THE PNEUMOGASTRIC NERVES BELOW
      THE DIAPHRAGM.

PMID- 19867031
TI  - EXPERIMENTAL CIRRHOSIS OF THE LIVER.
AB  - The reparative process which follows the wide spread necrosis of the dog's liver
      caused by the injection of haemagglutinative serum constitutes a chronic
      interstitial hepatitis of definite and constant character. This is not only a new
      type of experimental hepatic lesion, but is more definitely a cirrhosis than is
      any other experimental lesion hitherto described. It is of importance in
      explaining the histogenesis of cirrhosis, and incidentally various repair
      processes in the liver; but it does not aid in the elucidation of the etiology of
      cirrhosis in man, nor does it explain the peculiar arrangement of the new
      connective tissue in any form of human cirrhosis except possibly that associated
      with chronic passive congestion. It definitely demonstrates, however, that
      cirrhosis may follow extensive primary destructive lesions, a view not yet fully
      accepted, and supports the contention of Kretz that cirrhosis is essentially a
      reparative process.

PMID- 19867032
TI  - EXPERIMENTAL ARTERIOSCLEROSIS.

PMID- 19867033
TI  - ON THE PHYSIOLOGY OF HEART-BLOCK IN MAMMALS, WITH ESPECIAL REFERENCE TO THE
      CAUSATION OF STOKES-ADAMS DISEASE.
AB  - THE FACTS COLLECTED IN THE THIRD PART OF THIS PAPER JUSTIFY THE FOLLOWING
      CONCLUSIONS: (1) All of the cardinal symptoms of Stokes-Adams disease may be
      duplicated by heart-block resulting from a lesion in or near the auriculo
      ventricular bundle of His, and by this alone. (2) No typical case of Stokes-Adams
      disease has been described in which heart-block might not have been the cause of
      the trouble. (3) It can be shown that all cases of Stokes-Adams disease which
      have been studied by sufficiently accurate methods were cases of heart-block. (4)
      It would appear that heart-block without and with syncopal attacks are two stages
      of the same disease process.

PMID- 19867034
TI  - ON CERTAIN THERMOSTABILE VENOM ACTIVATORS.

PMID- 19867035
TI  - MORPHOLOGY AND PHYSIOLOGY OF AREAS OF LANGERHANS IN SOME VERTEBRATES.

PMID- 19867036
TI  - THE EFFECT OF INTRAVENOUS INJECTION OF SOLUTIONS OF DEXTROSE UPON THE VISCOSITY
      OF THE BLOOD.

PMID- 19867037
TI  - EFFECTS OF INTRAVENOUS INJECTIONS OF RADIUM BROMIDE.

PMID- 19867038
TI  - THE PHOTODYNAMIC ACTION OF EOSIN AND ERYTHROSIN UPON SNAKE VENOM.
AB  - Since the haemolysins of the several venoms respond differently to photodynamic
      action, they may be regarded as possessing different chemical constitutions. As
      regards stability, cobra haemolysin ranks first, daboia second, and Crotalus
      third. The toxicity of all the venoms is more or less diminished by eosin and
      erythrosin in sunlight. This reduction in toxicity depends upon chemical changes,
      of more or less profound nature, taking place in certain of the active principles
      of the venom. The more stabile the predominant active principles the less the
      reduction in toxicity, and vice versa. Venom-neurotoxins are highly resistant to
      photodynamic action, venom-haemolysins are less resistant, while the haemorrhagin
      and thrombokinase of Crotalus and daboia venoms exhibit weak powers of resistance
      to their action. Hence it follows that while cobra venom remained almost
      unaltered, rattlesnake and daboia venoms were greatly reduced in toxicity when
      mixed with the fluorescent dyes and exposed to sunlight. There is an interesting
      parallel between the action of eosin and erythrosin upon the different venoms and
      their reactions to other injurious agencies. For example, the haemolysins of
      cobra and daboia venoms are more heat resistant than the haemolysin of Crotalus
      venom, and the former are less injured by the dyes than the latter. The
      neurotoxin of the former venoms is also more heat stabile than that of the
      rattlesnake, and the same relative degree of resistance holds for this substance
      and the anilines. Just as the haemorrhagin of rattlesnake venom and the
      thrombokinase of daboia venom are destroyed by a temperature of 75 degrees C., so
      are they readily inactivated by the photo dynamic substances employed. The
      globulin-precipitating and blood corpuscle-protecting principle of cobra venom is
      relatively thermostabile and in contradistinction to the immunity-precipitins it
      is also unaffected by eosin and erythrosin. This study of the action of
      photodynamic substances upon snake venoms serves again to bring out the fact of
      their highly complex nature, and while enlarging somewhat the field in which
      photodynamic activity is known to operate, it also proves that this form of
      destructive activity is affected by the same conditions of resistance as confront
      the action of the usual physical and chemical agents.

PMID- 19867039
TI  - THE EFFECT OF EOSIN AND ERYTHROSIN UPON THE HAEMOLYTIC POWER OF SAPONIN.

PMID- 19867040
TI  - CONGENITAL CYSTIC KIDNEY AND LIVER WITH FAMILY TENDENCY.

PMID- 19867041
TI  - THE RESUSCITATION OF THE CENTRAL NERVOUS SYSTEM OF MAMMALS.
AB  - The cerebral circulation was interrupted for periods of three to eighty-one
      minutes by ligation of the innominate and left subclavian arteries proximal to
      the origin of the vertebral, in ninety-three cats. Eleven dogs were used in the
      earlier experiments. The eye reflexes disappear very quickly and a period of high
      blood pressure follows the occlusion immediately; vagus inhibition causes cardiac
      slowing and a fall in blood pressure, followed by a second rise after the vagus
      center succumbs to anaemia. Respiration stops temporarily (twenty to sixty
      seconds) after the beginning of occlusion, and then follows a series of strong
      gasps of the Cheyne-Stokes type, after which it stops until some time after the
      restoration of the cerebral circulation. The respiratory and vagus centers lose
      their power of functioning at approximately the same time. Asphyxial slowing of
      the heart may occur without the agency of the vagus center. The blood pressure
      slowly falls to a level which is maintained throughout the remainder of the
      period of occlusion. The anterior part of the cord and the encephalon lose all
      function; no reflexes are obtainable. The reflexes of the posterior part of the
      cord persist; the intravenous injection of strychnine does not affect the
      anterior part of the cord during the period of occlusion; but does affect the
      posterior portion of the cord. There is no secretion of tears or saliva, and the
      intra-ocular pressure is reduced. The blood pressure falls still more after
      release of the cerebra arteries, but soon begins to rise. The respiration returns
      suddenly, two to sixty minutes after restoration of the cerebral circulation, the
      first gasp being a strong one. The rate gradually increases until rapid enough
      for natural respiration. The eye reflexes and intra-ocular tension return more
      gradually, ten minutes to three hours after restoration of the cerebral
      circulation. The anterior part of the cord recovers its functions gradually. The
      first reflexes occur only on the same side as the stimulus, crossing of reflexes,
      to involve the other side, not occurring till later. As a rule, all reflexes
      return, and a short period of quiet follows. The anterior part of the cord again
      becomes irritable to strychnine, but succumbs to its action before the normal
      part. Spasms, of tonic, clonic, or mixed type, then appear, terminating in (a)
      death, (b) partial or (c) complete recovery. In partial recovery, disturbances of
      locomotion, such as walking in a circle, paralysis, dementia, loss of sight,
      hearing, and general intelligence, characterize the post-convulsive period. After
      complete recovery, there is a return to normal deportment. No gross lesions of
      the nervous system, other than a congested appearance of the previously anaemic
      area, were observed. Transection of the spinal cord stops the spasms below the
      level of section. Hemisection of the cord stops the spasms on the same side,
      below the level of section. Death, without any return of the reflexes after
      release of the cerebral arteries, has followed an occlusion of seven and one-half
      minutes. Respiration has returned after an occlusion of one hour. Five animals
      have recovered completely after an occlusion of seven minutes or more. Only one
      animal has recovered completely after an occlusion of fifteen minutes. No animal
      has recovered completely after an occlusion of twenty minutes. In Herzen's (26)
      resuscitation of an animal after several hours of cerebral anaemia, there must
      have been some anastomotic channels to the brain. Mayer's (27) limit of ten to
      fifteen minutes of cerebral anaemia, beyond which resuscitation is not
      practicable, is close to the correct one. It appears to us that, in cases of
      resuscitation two hours after cessation of the heart-beat, (Prus., loc.cit.) the
      auricles must have kept up a slow but, in some degree, an efficient movement of
      the blood through the brain. The truth of this suggestion might be tested by
      introducing some easily recognized, non-diffusible substance into a vein after
      the heart-beat ceases to affect a manometer, and later searching for it in the
      brain and other parts of the body. But, whatever the reason, cerebral anaemia in
      these cases must have been less complete than in our experiments. The
      histological alterations of the cord and brain are now being studied. The results
      will be published later.

PMID- 19867042
TI  - STUDIES UPON CALCAREOUS DEGENERATION : II. THE STAINING OF FATTY ACIDS AND SOAPS
      IN THE TISSUES BY FISCHLER'S METHOD, AND A MODIFICATION OF THE SAME. III.
      CALCIFICATIONS OF THE AORTA IN RABBITS AFTER THE INOCULATION OF ADRENALIN. IV.
      CALCIFICATIONS OF THE MEDIA IN ARTERIES OF THE ELASTIC TISSUE TYPE.

PMID- 19867043
TI  - THE INFLUENCE OF TEMPERATURE UPON THE RATE OF REACTION (HAEMOLYSIS,
      AGGLUTINATION, PRECIPITATION).

PMID- 19867044
TI  - THE FORMATION OF TRUE BONE WITH CELLULAR (RED) MARROW IN A SCLEROTIC AORTA.

PMID- 19867045
TI  - THE RELATION OF TYPES OF DIARRHOEA IN CHILDREN TO STRAINS OF BACILLUS
      DYSENTERIAE.

PMID- 19867046
TI  - STUDIES UPON THE INFLUENCE OF TENSION IN THE DEGENERATION OF ELASTIC FIBRES OF
      BURIED AORTAE.

PMID- 19867047
TI  - EXPERIMENTAL MYOCARDITIS; A STUDY OF THE HISTOLOGICAL CHANGES FOLLOWING
      INTRAVENOUS INJECTIONS OF ADRENALIN.

PMID- 19867048
TI  - THE ENZYMES IN PHAGOCYTIC CELLS OF INFLAMMATORY EXUDATES.

PMID- 19867049
TI  - THE TOXICOLOGICAL CONSTITUTION OF AMANITA PHALLOIDES.
AB  - From the experiments detailed in this paper it may be concluded that Amanita
      phalloides contains besides phallin, or the haemolytic principle of Kobert,
      another body of toxic nature. Phallin is thermolabile, and is destroyed by the
      action of pepsin and pancreatin. The other toxic body is thermostable and is
      resistant to pepsin and pancreatin. The two substances, moreover, possess
      different toxophoric and haptophoric groups, since an antiserum produced by the
      immunization of animals to the thermostable body has no neutralizing effects upon
      phallin. The thermolable body, phallin, produces the subcutaneous oedema and
      haemoglobinuria, and, in virtue of its blood-laking properties, the pigmentation
      of the spleen. The thermostable body produces haemorrhage and necrosis, and the
      fatty degeneration of the parenchymatous organs. The two bodies exist side by
      side in watery extracts of the fungus, but they cannot be considered as two
      constituents of a single poison exerting a variety of effects. To the haemolysin
      the name phallin has already been given by its discoverer, Kobert. For the
      thermostable substance described now for the first time, the name Amanito-toxin
      is proposed provisionally.

PMID- 19867050
TI  - CONCERNING THE MORPHOLOGY AND REPRODUCTION OF SPIROCHAETA PALLIDA AND A RAPID
      METHOD FOR STAINING THE ORGANISM.

PMID- 19867051
TI  - ON GLYCYLPROLIN ANHYDRIDE OBTAINED ON TRYPTIC DIGESTION OF GELATINE.

PMID- 19867052
TI  - ON THE PHOSPHOTUNGSTATES OF CERTAIN AMINOACIDS.

PMID- 19867053
TI  - A STUDY OF EPIDERMAL FIBRILS.
AB  - In certain animals, in addition to the protoplasmic fibrils of the stratum
      filamentosum that are present normally in human epidermis, there are well
      developed fibrils in the cells of the stratum germinativum. These fibrils are
      present in the human epidermis only under conditions of increased cell activity.
      These fibrils, that are prominent in the stratum germinativum of human epidermis
      under conditions of increased cell activity, seem to increase in direct ratio to
      rapidity of cell production. The differentiation of these fibrils of the stratum
      germinativum into the finer fibrils which connect the cells of the stratum
      filamentosum can be observed under proper conditions of growth and therefore
      there should be no separation of the fibrils into different groups with various
      names. This process of fibre production by the cells of the human epidermis is
      analogous to increased fibre production by various other cells under similar
      conditions, and may be of importance in identifying or classifying new growths of
      epithelial origin.

PMID- 19867054
TI  - ON THE INFLUENCE EXERTED ON THE VIRULENCE OF CARCINOMA IN MICE BY SUBJECTING THE
      TUMOR MATERIALS TO INCUBATION PREVIOUS TO INOCULATION.

PMID- 19867055
TI  - STUDIES UPON CALCAREOUS DEGENERATION : V.-THE RELATION OF EXPERIMENTAL ARTERIAL
      DISEASE IN ANIMALS TO ARTERIOSCLEROSIS IN MAN.

PMID- 19867056
TI  - THE PATHOGENESIS OF EXPERIMENTAL COLITIS, AND THE RELATION OF COLITIS IN ANIMALS
      AND MAN.
AB  - 1. The facts described in this paper are intended to bear upon the pathogenesis
      of colitis in man and animals. 2. The toxin of the Shiga dysentery bacillus is
      liberated from the bacillus through the process of autolysis. 3. In rabbits the
      toxin is not absorbed directly in an active form by the gastro-intestinal tract;
      in man, however, absorption of an active poison does take place from the
      intestine. 4. The toxin is excreted in rabbits, and probably in man as well by
      the intestine, chiefly probably by the large intestine, which being injured by
      the act of elimination, reacts by the development of inflammation, etc. 5. In
      rabbits the characteristic action of the toxin depends upon the integrity of the
      biliary secretion into the intestine. When the bile is prevented from entering
      the intestine, either by ligature and section of the duct or by establishment of
      a biliary fistula, no lesions whatever of the large intestine appear, or they are
      inconsiderable in extent. 6. The loss of toxin through a biliary fistula does not
      prevent in rabbits the lethal effects which are caused, apparently, by a nervous
      poison. The tying off of the bile duct seems to prevent the passage of the toxin,
      in amounts sufficient to cause the large intestinal lesions, into the blood. The
      liver, therefore, in this condition tends to hold back the toxin from the general
      circulation. 7. The peculiar effects of the toxin on the large intestine in
      rabbits is not produced at once, but would appear to depend upon successive acts
      of excretion of the poison by the bowel. 8. The establishment of biliary fistula
      reduces the intensity of action of corrosive sublimate upon the large intestine
      in rabbits; and the lesions of ricin poisoning in these animals are also modified
      by this operation. 9. Dysentery toxin is destroyed by peptic digestion, and also,
      though probably more slowly, by tryptic digestion. The absence of power of the
      toxin to cause poisoning in rabbits when it is brought directly into the lumen of
      the intestine, is not explained by the destructive action of trypsin. 10. The
      character of the histological changes in the caecum of rabbits caused by the
      dysentery toxin points to an action upon the substance and not primarily upon the
      surface of the intestine.

PMID- 19867057
TI  - SOLUTION OF TISSUE WITH ABSCESS.

PMID- 19867058
TI  - A SIMPLE METHOD FOR THE PLATING OF ANAEROBIC ORGANISMS.

PMID- 19867059
TI  - THE INFLUENCE OF COLLOIDS UPON THE DIFFUSION OF HAEMOLYSINS.
AB  - Acids, alkalies, salts, glucosides, and certain toxins diffuse more quickly into
      0.9 per cent. salt solution than into agar-agar and gelatin suspensions. The
      inhibitory effect of the colloids grows with increase in concentration, which
      increase affects both the velocity and extent of the diffusion. In the case of
      gelatin the degree of diffusion is approximately in inverse proportion to the
      square root of the concentration. Agar-agar in strengths up to 2 per cent.
      inhibits far less than gelatin in 10 per cent. suspensions; and the difference in
      degree of inhibition exercised by 0.5 per cent. and 2 per cent. agar-agar is a
      small one. Haemolytic substances diffuse from gelatin into agar-agar more slowly
      than from saline into agar-agar. But the velocity of diffusion from agar-agar
      into gelatin is greater than from saline into gelatin. The effects of differences
      in concentration of the haemolytic agent vary according to the agent and the
      manner of its solution. When the haemolyser is dissolved in salt solution the
      diffusion of 1/100 N. and 1/1000 N. solutions (saponin) is almost identical;
      while with solanin the stronger solutions diffuse faster. When the haemolyser is
      dissolved in the colloid diffusion into fluid media is nearly proportional to the
      concentrations of the haemolytic agent. The velocity of diffusion into and from
      colloids is in general proportional to the square root of the time. Acids,
      alkalies, salts, and glucosides act in a manner which is in agreement with this
      rule. Cobra lysin and tetanolysin do not act in conformity with the rule. Cobra
      lysin appears to diffuse into colloids more slowly, proportionally, than cobra
      neurotoxin, and tetanospasmin more slowly than tetanolysin. The biological method
      described in this paper for studying diffusion in colloids is applicable to
      haemolytic and some other toxic substances, and, with accuracy possibly only to
      such substances possessing relatively simple compositions. Since all diffusion in
      the living body takes place within colloidal media of different concentrations,
      it would seem desirable to perfect methods through which the interaction of toxic
      chemicals and the fluids and cells of the body may in a manner be imitated in
      vitro. Through this means our knowledge of toxicology may well be extended.

PMID- 19867060
TI  - CLINICAL AND EXPERIMENTAL OBSERVATIONS UPON CHEYNE-STOKES RESPIRATION.
AB  - IN ADDITION TO THE RESULTS BROUGHT OUT IN THE SEPARATE SECTIONS I WISH TO DIRECT
      ESPECIAL ATTENTION TO THE FOLLOWING CONCLUSIONS: (1) In ten cases of Cheyne
      Stokes respiration observed clinically, the alternate periods of respiratory
      activity and apnoea were associated with Traube-Hering waves of blood pressure.
      These cases may be separated into two groups characterized by the relation of the
      respiratory changes to the changes of blood pressure. In one group the period of
      respiratory activity was associated with a rise of blood pressure, the period of
      apnoea with a fall; in the other group, the reverse relations existed. The former
      group included two cases of Cheyne-Stokes respiration occurring with increased
      intracranial tension; the latter contained eight cases with cardiac and arterial
      disease. (2) By means of cerebral compression, periodic respirations may be
      produced experimentally, and the relation of the blood pressure changes to the
      respiratory variations are the same as in the clinical cases with increased
      intracranial tension, namely, a rise of pressure with each group of respirations
      and a fall with each period of apnoea. In the experiments, during each
      respiratory group, the blood pressure rises above the line of intracranial
      tension and with each period of apnoea it falls below this line. With the
      disappearance of this relation, the periodicity of the respirations likewise
      disappears. It is probable that the same relation between the blood pressure and
      intracranial pressure exists when Cheyne-Stokes respiration occurs clinically in
      association with increased intracranial tension. (3) Disappearance of the
      periodic respiratory activity in the clinical cases of both groups is accompanied
      by disappearance of the waves of blood pressure. (4) The waves of blood pressure
      cannot be regarded as a mechanical effect of the periodic respiratory activity;
      on the contrary the latter must be due to the changes of blood pressure, or both
      phenomena may be referable to a common cause. (5) Cheyne-Stokes respiration in
      states of increased intracranial tension, with blood pressure waves rising and
      falling above and below the line of intracranial tension, is due to periodic
      activity of the respiratory, vasomotor, and cardio-inhibitory centres, the
      underlying cause of which is an alternate anaemia and blood supply to the
      medullary centres. The vasomotor centre, as the result of periodic increase and
      decrease of the stimulus, shows periodic variations in its activity. It is
      stimulated to greater activity during the periods of anaemia, and partially
      relaxes with each period of blood supply. During the periods of anaemia, the
      respiratory centre loses its irritability for the acting stimulus, and is
      therefore apnoeic. It is finally stimulated to activity, either as a result of an
      increase in its irritability from a preceding rise of blood pressure, or from a
      great increase in the respiratory stimulus. The cardio-inhibitory centre is
      stimulated by the periods of anaemia. This stimulation causes slowing of the
      pulse, which passes off to a considerable extent with the following period of
      blood supply. (6) Cheyne-Stokes respiration has heretofore been regarded as
      always the manifestation of the same conditions and capable of the same
      explanation; the results of this work, on the contrary, show that two distinct
      groups of cases may be recognized, depending upon the relation of the blood
      pressure changes to the periodic respiratory activity.(19) (7) The medullary
      centres show great differences in their susceptibility to anaemia. The
      respiratory centre is very susceptible to a much reduced blood supply; its
      irritability is rapidly reduced or lost upon the occurrence of marked or complete
      anaemia, and is rapidly regained when the blood supply is renewed if the anaemia
      has not been maintained too long. The effect of a considerable anaemia upon this
      centre is entirely different from that of a normal or somewhat reduced supply of
      blood which is more venous than normal, that is, contains more carbon dioxide and
      less oxygen, such as occurs with ordinary asphyxia. The vasomotor and cardio
      inhibitory centres are not nearly so susceptible to anaemia. The former centre
      may, and frequently does, respond when in a condition of complete anaemia. (8) I
      am able to confirm, as a result of my experiments upon cerebral compression, in
      all essential details the conclusions of Cushing, and the general law formulated
      by him, namely that "an increase of intracranial tension occasions a rise of
      blood pressure which tends to find a level slightly above that of the pressure
      exerted against the medulla."

PMID- 19867061
TI  - THERAPEUTIC EXPERIMENTS WITH ANTICROTALUS AND ANTIMOCCASIN SERA.
AB  - 1. The action of different antivenins is highly, although not absolutely,
      specific for the venoms for which they are prepared. The antivenomous effect is
      demonstrable by experiments on toxicity (in vivo) and on haemolysis (in vitro).
      2. Anticrotalus and antimoccasin sera possess therapeutic properties of high
      degree. By their employment before the stage of extreme prostration has been
      reached, poisoned guinea-pigs can be saved. 3. The standardization of antivenins
      must be made separately for the antitoxic and antihaemolytic actions, since these
      do not bear a constant and invariable relation to each other.

PMID- 19867062
TI  - EXPERIMENTAL ANAEMIAS IN THE RABBIT.

PMID- 19867063
TI  - AN IMPROVED SYRINGE FOR INJECTING PRECISE AMOUNTS.

PMID- 19867064
TI  - A CONTRIBUTION TO THE STUDY OF THE OPSONINS.

PMID- 19867065
TI  - THE INFLUENZA BACILLUS IN INFLAMMATIONS OF THE RESPIRATORY TRACT IN INFANTS.

PMID- 19867066
TI  - THE EFFECTS OF INTRASPINAL INJECTION OF MAGNESIUM SALTS UPON TETANUS.
AB  - Intraspinal injections of magnesium sulphate, in doses which do not affect the
      respiratory centre or other vital function, are capable of abolishing completely
      all clonic convulsions and tonic contractions in cases of human tetanus, and
      experimental tetanus in monkeys. The relaxing effects of the injections may last
      twenty-four hours or longer. In experimental tetanus in monkeys early intraspinal
      injections of magnesium salts are capable of retarding the progress and
      development of the tetanic symptoms.

PMID- 19867068
TI  - AN EXPERIMENTAL RESEARCH INTO THE RESUSCITATION OF DOGS KILLED BY ANESTHETICS AND
      ASPHYXIA.

PMID- 19867067
TI  - THE OCCURRENCE OF SPECIFIC IMMUNITY PRINCIPLES IN THE BLOOD OF VACCINATED CALVES.

PMID- 19867069
TI  - THE THERMOSTABILE ANTICOMPLEMENTARY CONSTITUENTS OF THE BLOOD.
AB  - Blood serum contains normally certain principles which inhibit serum haemolysis
      by interfering with the action of complement. In the case of most sera the
      anticomplementary action appears only after heating to 56 degrees C. or higher.
      The inhibiting action of this principle is directed against alien as well as
      native complements, and is non-specific in character. It would appear as if the
      inactivation of serum at 50 degrees C. or thereabouts were due to a partial
      liberation of the antilytic principle which just about suffices to neutralize the
      action of the native complement. As the temperature of the serum is raised, up to
      a certain point, more and more of the antilysin is set free until the serum comes
      to contain an overplus, in excess of the quantity neutralizing its own
      complement, which is capable of interfering with the action of additional native
      or alien complements. Serum heated to 90 degrees C. is less antilytic than serum
      heated to 70 degrees C., either because the antilysin has entered into new, more
      stable compounds which prevent its action, or, as is more probable, because of
      the liberation from the serum of a second group of principles in themselves
      haemolytic directly, or indirectly by increasing the power of serum haemolysins
      (auxilysins). This latter action tends to mask and to suppress the inhibitory
      influences of the antilysin. The antilysin is removed from serum by digestion
      with many kinds of blood corpuscles which, apparently, absorb the principle.
      While, by reason of this treatment, the serum is deprived of its inhibitory
      power, the corpuscles have acquired greater resistance to serum haemolysins. By
      treating blood serum and corpuscles with ether the antilysin can be extracted.
      The ethereal extract, freed from lecithin and certain related bodies, contains
      the antilysin in a concentrated but not in a pure form, which can now be taken up
      in saline solution in which it dissolves. The saline solution of the antilysin,
      which for convenience has been denominated "protectin," behaves in all respects
      like the native antilytic sera except that it is uninfluenced by temperatures of
      90 degrees C. or even higher temperatures. Protectin inhibits serum haemolysis
      directly by neutralizing complement and indirectly after absorption by corpuscles
      by increasing their resistance. Hence it is highly probable that the antilytic
      principle of heated serum and protectin extracted from serum and corpuscles are
      the same substance. Thermostability is one of the characteristic properties of
      protectin. Serum and corpuscles, first dried, may be heated to 150 degrees C.
      without losing the protecting principle, and the principle persists in such
      heated products for at least two years. Protectin in solution is unaffected by a
      temperature of 100 degrees C. maintained for one hour, and suffers only slight
      reduction in activity at the expiration of two hours; while temperatures ranging
      from 135 degrees to 150 degrees C. bring about marked reduction in protective
      power. As these alterations are produced by high temperatures the reaction of the
      solution changes from acid, through neutral, to alkaline.

PMID- 19867070
TI  - CALCIFICATION OF THE BREAST FOLLOWING A TYPHOID ABSCESS.
AB  - 1. In a patient with typhoid fever, who had taken, during eleven days, 132
      grammes of lactate of calcium by the mouth, as well as 5 grammes of chloride of
      calcium subcutaneously, there developed, eleven days after the subcutaneous
      infusion, a large abscess of the breast from which Bacillus typhosus and
      Staphylococcus aureus were obtained on culture. The abscess was opened and the
      wound packed with iodoform gauze. Eleven days later a deposit of calcium appeared
      in the granulation tissue bordering the wound. This rapidly increased until the
      rim of the opening and the lining granulation tissue were converted into a hard,
      calcareous mass. A number of nodules of an apparently similar character appeared
      in other parts of the breast. 2. A month later the iodoform packing was removed
      and the patient was put on a carbohydrate free diet. This was continued for
      twenty-four of the next thirty-six days. Under this treatment the abscess almost
      entirely healed with complete disappearance of the deposit of calcium. 3. Studies
      of the intake and output of calcium showed that, during three days under a diet
      of milk and eggs there was a material calcium retention ((I).346 grammes) : (b)
      That during two periods amounting to three weeks in all, under a carbohydrate
      free diet, there was an excess of Ca elimination over the intake of 3.672
      grammes, (c) That during ten days following the last carbohydrate free period,
      under a normal diet, there was a retention of calcium amounting to 0.602 gramme.
      4. The disappearance of calcium from the breast was associated in time with the
      carbohydrate free diet and the excessive elimination of calcium. 3. Under the
      carbohydrate free diet acetone and diacetic acid appeared on two occasions in the
      urine, but were not accompanied by any increase in the elimination of calcium. 6.
      With regard to the cause of the calcification, we cannot speak with certainty.
      The remarkable association of the deposition of calcium at the seat of an
      injection of calcium chloride in an individual who had been receiving large
      quantities of lactate of calcium by the mouth-a deposition occurring in tissues
      which were in direct connection with or in the immediate neighborhood of a
      dressing containing iodoform, a poison which in certain animals produces
      degenerative changes in the kidneys and liver which are peculiarly prone to
      calcification, is striking and worthy of note. 7. In how far the decalcification
      of the affected area may have been due to the carbohydrate free regime with the
      consequent excess in calcium elimination, it is impossible, on the basis of a
      single case, to say. The coincidence in time of the disappearance of calcium from
      the breast with this treatment is, however, remarkable and extremely suggestive.

PMID- 19867071
TI  - TOXINS AND ANTITOXINS--SNAKE VENOMS AND ANTIVENINS.
AB  - A specific antivenin against crotalus venom can be prepared bv the immunization
      of goats. A specific antivenin against water moccasin venom can be produced by
      the immunization of goats with this venom, modified by hydrochloric acid.
      Immunization with the unmodified venom is very difficult. The toxicity of
      crotalus venom is diminished more than fifty percent. by passage through a
      Chamberland filter. There is a simple relation between the toxicity and the body
      weight for guinea-pigs weighing from 250 to 500 grams. Smaller guinea-pigs (125
      grams) are comparatively less resistant. The toxicity is smaller by subcutaneous
      than by intraperitoneal injection (guinea-pigs), or by intravenous injection
      (rabbits). White rats are very resistant. The toxicity of cobra venom is not
      measurably diminished by filtration through a Chamberland filter. The relation
      between the amount of venom and the corresponding time of death is very regular,
      and can be expressed by a curve of asymptotic nature. Lecithin does not increase
      the toxicity. The tracings representing toxin-antitoxin neutralization for the
      three venoms (crotalus, cobra and moccasin) show deviation from the straight
      line. This deviation is most pronounced for the toxic quota of the venoms. The
      tracing representing crotalus venomantivenin neutralization, determined on guinea
      pigs, can, within errors of experiment, be expressed by the equation: Free toxin
      . Free antitoxin = K . toxin-antitoxin. The corresponding tracing determined on
      rabbits is somewhat different, but both tracings are much more markedly curved
      than that for cobra venom-antivenin. The neutralization tracing of water moccasin
      venom shows the peculiarity, that small amounts of antivenin decrease the
      toxicity to a minimum, but the toxicity is again increased by further addition of
      antitoxin. The tracing representing neutralization of the haemolysins of the
      three venoms are different from the tracings of neutralization of the toxins, and
      approach very closely to a straight line. Still, in all instances, the
      determinations with great concentrations of antilysin show pronounced deviation,
      perhaps due to some dissociation of the toxin-antitoxin combination.

PMID- 19867072
TI  - EXPERIMENTS ON THE LEUKOLYTIC ACTION OF THE BLOOD SERUM OF CASES OF LEUKAEMIA
      TREATED WITH X-RAY AND THE INJECTION OF HUMAN LEUKOLYTIC SERUM IN A CASE OF
      LEUKAEMIA.

PMID- 19867073
TI  - OBSERVATIONS ON THE CYTOLOGY OF MULTIPLE NON-INFLAMMATORY NECROSIS OF THE LIVER
      AND ON CERTAIN RELATED DEGENERATIVE CHANGES IN CELLS.

PMID- 19867074
TI  - EXPERIMENTAL ATRESIA OF THE URETER.
AB  - Previous investigators have found that complete occlusion of the ureter may lead
      either to hydronephrosis or to atrophy. In Lindemann's series of six dogs;, for
      instance: Two animals showed simple hydronephrosis, three animals showed simple
      atrophy, and in one animal the kidney was slightly enlarged and the ureter and
      pelvis dilated, but fluid was absent. In his series of four rabbits, all showed
      hydronephrosis. The result, whether hydronephrosis or atrophy, is evidently not
      determined by the time elapsing after the operation. Lindemann found that the
      intrapelvic pressure resulting from the ligation obliterates the lumen of the
      vessels, first of the veins and subsequently of the arteries; but that this is
      compensated by an increase of the collateral blood supply through the capsule,
      the degree of this compensation determining the presence or absence of
      hydronephrosis. If the blood supply is free, the fluid after tapping will
      accumulate again and again. It is somewhat remarkable that all of our dogs showed
      hydronephrosis after the first operation. The results of establishing a urinary
      fistula differed in the two cases in which it was tried: The fluid did not re
      form in Dog 3 even when sodium sulphate was injected: whereas in Dog 4, a very
      abundant quantity of fluid reaccumulated spontaneously; but it differed notably
      in composition from the original fluid, having more the character of a purulent
      inflammatory exudate. The histological changes consist in necrosis of the renal
      cells, obliteration of the glomeruli, increase of connective tissue, and
      endarteritis and periarteritis. Different areas in the same kidney are affected
      in very different degree, some areas appearing almost normal. The glomeruli are
      generally less altered than the tubules. The collecting tubules are generally
      displaced so as to run parallel to the surface; many are dilated. The changes
      correspond closely to those described by Lindemann. The sound kidneys showed
      slight hyperaemia and hypertrophy, but no necrosis. This corresponds with the
      findings of Pearce and of Ames. The uniformity in chemical composition of the
      fluid obtained, after the first operation, from the four dogs, as shown by Column
      III of Table I, is very striking, and points to a uniform origin by a process
      which is but little affected by the interval elapsing after the operation. The
      specific gravity, total solids and proteids correspond to those of a very dilute
      lymph, being but a trifle above those of cerebro-spinal fluid and aqueous humor,
      and much lower than those of serum, lymph and most cystic fluids (the proteid
      content of the latter being generally from 2 to 6.5 per cent.). The human fluid
      (Column II) which had remained in the kidney for a very long time had a
      particularly low proteid percentage; while that of the second fluid of Dog 4
      (Column VIII) was very much higher; this last fluid having a pronounced
      inflammatory character and being of recent formation. The absence of notable
      amounts of the specific urinary constituents is particularly important.(4)
      Odorous principles are entirely absent. Urinary pigments appear to be present in
      the four dogs' urines, but absent from the human case,(5) and after the second
      operation in case of the dogs. It seems fair to assume that the pigments were
      secreted shortly after the ligation, when the kidneys were still functional, and
      that they were reabsorbed with extreme slowness. Urea was present in all the
      fluids, but its quantity was very small in the dogs, and probably in the human
      case. It is on the whole somewhat greater than in the serum (0.103 per cent., in
      place of 0.05 per cent.), but the difference may be within the analytical error.
      The same applies to the ammonia, phosphates and sulphates. An important
      difference between these fluids on the one hand and blood serum, lymph and
      ordinary exudate on the other, lies in the higher contents of chlorid, and the
      consequently greater molecular concentration. The ordinary chlorid content of
      body fluid varies between 0.55 and 0.70 per cent., mean about 0.6 per cent (as
      NaCl), while that of the first kidney fluid, in the dogs, varied between 0.68 and
      0.75 per cent., mean 0.725 per cent.; that of the human fluid was 0.83 per cent.,
      that of the second fluid of Dog 4 only 0.52 per cent. The depression of the
      freezing point in the human case was 0.715 degrees C., as against the normal
      value, for human serum, of 0.491 to 0.562. (Possibly the blood of this patient
      had a higher concentration than normal, since uraemia existed.) The high chlorid
      percentage has evidently no relation to the length of time during which the fluid
      sojourned in the kidney. It is probably to be explained by the relatively slow
      absorption of this ion from the kidney pelvis. It is also to be remarked that
      cerebrospinal fluids generally have a somewhat high chlorid content (0.573 and
      0.6 per cent.), but this never reaches the height of these ureteral fluids.

PMID- 19867075
TI  - HYDRONEPHROSIS OF RIGHT KIDNEY, CONGENITAL ATRESIA OF LEFT URETER, AND MARKED
      ATROPHY OF LEFT KIDNEY.

PMID- 19867076
TI  - THE ELECTRICAL CHARGE OF TOXIN AND ANTITOXIN.
AB  - 1. Both diphtheria and tetanus toxin and their antitoxins arc electro-positive,
      that is, they pass to the cathode under the influence of an electric current. 2.
      The character of the charge is not altered by a change in the reaction of the
      solvent. 3. The combination of toxin and antitoxin would seem to represent not a
      true chemical reaction but the adsorption of one colloid by another.

PMID- 19867077
TI  - AN EXPERIMENTAL STUDY INTO THE CAUSE OF THE INCREASED PORTAL PRESSURE IN PORTAL
      CIRRHOSIS.
AB  - 1. In the liver of portal cirrhosis there is a far freer communication between
      the arterial and portal currents than in the normal liver. 2. Factors
      contributing to the increased portal pressure in portal cirrhosis are (1) the
      direct communication of the arterial pressure to the portal vessels through
      dilated capillaries, (2) the larger volume-flow of the hepatic artery in
      proportion to the portal flow in cirrhosis as compared to that in the normal
      liver. 3. A portal cirrhotic liver gives passage to an amount of portal fluid
      proportionate to .its weight. There is no obstruction to the portal vessels from
      fibrosis in the large portal cirrhotic liver. 4. From an arterial inflow there is
      a free return flow through the portal as well as through the hepatic veins in
      both normal and cirrhotic livers. 5. From a portal inflow the return is through
      the hepatic vein only. The Gad's theory of valves and the arterial capillary
      network account for this fact. 6. The portal pressure has a decided influence on
      the arterial volume-flow and vice versa. This influence is more marked in the
      cirrhotic than in the normal liver. 7. The communication of the arterial pressure
      to the portal pressure is an important factor in an explanation of the increased
      portal pressure in portal cirrhosis.

PMID- 19867078
TI  - CONTRIBUTIONS TO THE BIOLOGY OF DIPLOCOCCUS INTRACELLULARIS.

PMID- 19867079
TI  - EXPERIMENTAL CEREBRO-SPINAL MENINGITIS IN MONKEYS.

PMID- 19867080
TI  - CONCERNING A SERUM-THERAPY FOR EXPERIMENTAL INFECTION WITH DIPLOCOCCUS
      INTRACELLULARIS.

PMID- 19867081
TI  - A CONTRIBUTION TO THE BACTERIOLOGY OF RHEUMATIC FEVER.
AB  - The conclusions I would draw from this work are merely those stated in a former
      paper. 1. The results obtained by injections of streptococci are different from
      those produced by Micrococcus rheumaticus. 2. Micrococcus rheumaticus cannot be
      regarded as an attenuated streptococcus, nor acute rheumatism as an attenuated
      streptococcal pyaemia. 3. In uncomplicated cases of acute rheumatism the organism
      may not be found in the blood or in the joint exudates.

PMID- 19867082
TI  - LEUCOPROTEASE AND ANTI-LEUCOPROTEASE OF MAMMALS AND OF BIRDS.
AB  - The inhibiting action of the blood serum upon the enzyme of the polynuclear
      leucocytes, leucoprotease, is exerted by the albumin fraction of the serum. The
      albumin fraction contains no proteolytic enzymes. The globulin fraction of the
      serum contains no anti-enzyme for leucoprotease; it contains, on the contrary, an
      enzyme which digests proteids in a neutral or alkaline medium. This enzyme
      resembles leucoprotease which is present in the polynuclear leucocytes of an
      inflammatory exudate and in the bone marrow from which these cells are derived,
      and is doubtless identical with the similar enzyme occurring in smaller quantity
      in the spleen. This enzyme which is present in the blood serum is held in check
      by its anti-enzyme, but the latter is in such excess that the serum as a whole is
      capable of checking the action of leucoprotease when added in considerable
      quantity. Leucoprotease of one mammalian species is inhibited by sera of other
      mammalian species, but the anti-enzymotic activity of various sera differs; the
      anti-enzyme of the rabbit's serum is stronger than that of dog's serum, when
      tested either with dog's or with rabbit's leucoprotease. The co-existence in the
      rabbit of leucoprotease with feeble strength and anti-body of great activity may
      explain the absence in these animals of typical suppuration with liquefaction of
      tissues. The serum of birds which have been tested, namely, pigeon and hen,
      almost completely fails to inhibit mammalian leucoprotease (of dog). The
      polynuclear leucocytes, the bone marrow and the spleen of the hen do not contain
      an enzyme resembling leucoprotease of mammals. The absence of anti-enzyme in the
      serum is associated with absence of a corresponding enzyme in the leucocytes.

PMID- 19867083
TI  - ON THE ELECTRICAL CHARGE OF THE NATIVE PROTEINS AND THE AGGLUTININS.
AB  - 1. Tetanolysin and antitetanolysin travel toward the cathode under the influence
      of an electric current. 2. The specific agg-lutinins are electro-positive. 3. The
      proteid matter of serum is not amphoteric but travels toward the cathode whether
      its reaction be acid, neutral, or alkaline. 4. The bacteria-agglutinin
      combination may be disassociated by means of the electric current.

PMID- 19867084
TI  - HETEROTRANSPLANTATION OF BLOOD VESSELS PRESERVED IN COLD STORAGE.
AB  - The experiments show merely that blood vessels transplanted from dog to cat can
      act as arteries for seventy-seven days at least; and that having spent several
      days in cold storage does not interfere with their ordinary functions. The
      animals operated upon must, however, be kept under observation for several
      months, or, indeed, for several years, before any conclusion can be drawn
      concerning the practicability of this method of preservation and
      heterotransplantation of blood vessels.

PMID- 19867085
TI  - NUCLEIN METABOLISM IN A DOG WITH ECK'S FISTULA.

PMID- 19867086
TI  - THE EXPERIMENTAL VASCULAR LESIONS PRODUCED BY BACILLUS MALLEI.
AB  - 1. Bacillus malleiand its poison produce a variety of vascular lesions in the
      rabbit and the guinea pig. 2. The type of the lesion depends upon, (a) the
      virulence of the culture, (b) the sex of the animal and (c) the degree of
      acquired immunity. 3. The vascular changes of a proliferative and degenerative
      nature produced by the slow action of the glanders poison in rabbits and guinea
      pigs are analogous to the vascular lesions caused by sub-acute glanders infection
      in man. 4. The most common site of the glanders vascular lesions of animals and
      man is the peripheral vessels, and especially the smaller visceral arteries. 5.
      The aorta is a less common site of the experimental lesions. 6. The vascular
      lesions produced experimentally by Bacillus mallei and its poison consist of
      three processes, (a) exudation, (b) proliferation, (c) degeneration. 7. The
      lesions produced by sub-acute glanders in man consist of two processes,
      proliferation and degeneration. 8. The primary reaction of the vessels in
      experimental animals and in sub-acute human glanders consists of a proliferation
      of the endothelium of the intima. 9. The first degenerative changes observed in
      experimental animals and in sub-acute human glanders occur in the "innermost
      layer" of the media and not in the so-called " middle zone." 10. The cause of the
      degenerative change in the inner layer of the media appears to be interference
      with the nourishment of the circular muscle fibres of the media by proliferation
      of the endothelium of the intima.

PMID- 19867087
TI  - ELECTRIC CHARGES CARRIED BY THE HEMOLYSINS.

PMID- 19867088
TI  - RESULTS OBTAINED BY THE INJECTION OF PLACENTA INTO ANIMALS OF THE SAME AND OF
      DIFFERENT SPECIES.
AB  - The injection of rabbits' placenta into rabbits produces no isoprecipitins. From
      the incomplete experiments performed it would appear that placental injections
      into animals of the same species cause no changes in the generative organs.
      Further research into this question will be pursued. The injection of human
      placental nucleo-proteid, prepared from placental tissue made nearly blood free,
      does not produce an antiserum. This result confirms the conclusions of Pearce and
      Jackson, that nucleo-proteids act merely as mild toxic agents, without specific
      qualities. The injection, into rabbits, of human placental tissue, rendered
      practically blood-free, fails to produce any specific reaction. This confirms the
      view that the serum reaction following the injection of cells into a foreign
      organism is largely due to the blood contained in the injected tissues. The
      injection into rabbits, of the human placenta, made nearly blood-free, produces a
      weak " human reaction " which can be demonstrated by the reactions for
      precipitin, deflection of complement, agglutinin, and hemolysis. No specific
      placental reaction can be shown. This is in strict accord with the view that
      cytotoxines are not specific; that there is no morphological specificity. The
      anti-sera obtained showed no cytolytic action; therefore no specific
      syncytiolytic action could be demonstrated. If the information obtained in this
      investigation is applied to the theory of Halban, it will be noted that no
      experimental proof of the specific action of placental tissue upon the female
      generative organs could be demonstrated. The number of experiments performed,
      bearing upon this one point, were however too few to permit of a definite and
      final opinion. The work dealing with Veit's ingenious hypothesis was more
      complete and carried out by many methods, which would necessarily act as a check
      upon one another. As the results of all these experiments were in complete
      harmony, I feel justified in making a positive statement that no experimental
      proof of a specific placental immune reaction can be demonstrated by our present
      biological methods. Whether Veit's hypothesis, thus deprived of its biological
      proof, must in consequence be discarded, is a question which I do not consider
      myself competent to answer.

PMID- 19867089
TI  - THE NATURE OF THE ANTITETANIC ACTION OF EOSIN.
AB  - Eosin, if present in cultures containing tetanus spores, prevents the germination
      of these spores when its concentration (in glucose bouillon) reaches 0.2 per
      cent. When the concentration of the eosin sinks to 0.01 per cent., germination of
      the spores is no longer inhibited, but the vegetative bacilli developed from the
      spores execute a highly restrained form of multiplication. When the eosin
      concentration sinks to 0.001 per cent., vegetation and multiplication of the
      bacilli become more active, but no new spores are formed even after long periods
      of time. With glucose agar it is not until the concentration of the eosin in the
      cultures falls to .05 per cent. that sporulation again appears. At this
      concentration of the eosin, very few spores are formed ; but as the eosin sinks
      lower and lower, sporulation becomes more active, until with 0.001 per cent. it
      is essentially of normal degree. In concentrations of 0.003 per cent., eosin
      prevents perfect segmentation of the multiplying bacilli, with the result that,
      finally, long and convoluted threads of bacilli are produced. The spores which
      are formed in a medium containing 0.01 per cent. of eosin are often situated at
      the centre and not at one pole of the bacilli. Eosin in a strength of 2 per cent.
      is capable of destroying the vegetative bacilli, if the contact is prolonged to
      fifteen minutes, and in strength of 0.1 per cent., in twenty-four hours. Placing
      this latter mixture of bacilli and eosin in the sunlight greatly hastens the
      bactericidal effect, and the bacilli are found to be incapable of growth at the
      end of several hours. Eosin in high concentrations is not capable of killing the
      tetanus spores, even after long exposure to sunlight (thirty hours). The toxin
      production of tetanus bacilli grown in eosinized culture media diminishes as the
      concentration of the eosin increases. This effect is brought about partly by the
      restraining action of the dye on vegetation, and partly by its detoxicating
      action upon the poison., The toxin-producing power and the virulence of tetanus
      bacilli are not permanently modified by contact with eosin for a long period, or
      by successive cultivations in eosinized media. Eosin is likewise capable of
      restraining the vegetation of tetanus spores in the animal body. In spore threads
      inserted beneath the skin of rats, and surrounded with eosin in solution, a very
      restricted vegetation takes place. If the injections of eosin are repeated.
      vegetation soon ceases and the vegetated bacilli degenerate and disappear. The
      ungerminated tetanus spores remain alive in a latent condition indefinitely in
      the healed wound beneath the skin. These spores do not lose power to grow outside
      the body, or inside the body of animals under favorable conditions, or to produce
      toxin in a characteristic manner.

PMID- 19867090
TI  - LOCAL IMMUNITY TO TETANUS IN INOCULATED RATS TREATED WITH EOSIN.

PMID- 19867091
TI  - PHYSIOLOGICAL AND PHARMACOLOGICAL STUDIES OF MAGNESIUM SALTS : V. THE INFLUENCE
      OF NEPHRECTOMY UPON THEIR TOXICITY.

PMID- 19867092
TI  - THE INFLUENCE OF SALICYLIC ACID UPON URICOLYSIS.

PMID- 19867093
TI  - ON THE FUNCTION OF THE POSTERIOR SPINAL GANGLIA.

PMID- 19867094
TI  - THE PATHOGENESIS OF GALL STONES.

PMID- 19867095
TI  - MULTIPLE MYELOMA: A HISTOLOGICAL COMPARISON OF SIX CASES.
AB  - A histological study of six cases of myeloma shows a striking similarity of cell
      structure with differences of minor degree. The common characteristics of the
      cells are a finely granular, slightly basophilic cytoplasm, an eccentrically
      placed nucleus, a nucleolus, centrosomes, a nuclear membrane and a tendency to
      mural arrangement of the chromatin. With these characteristics there is a greater
      resemblance of the tumor cells to bone marrow plasma cells than to myelocytes. In
      most of the cases reported by other observers the cells show these
      characteristics and these tumors form a group within which the cells of
      individual cases show no greater variation than occurs in other tumor groups.

PMID- 19867096
TI  - THE HISTOLOGICAL LESIONS OF EXPERIMENTAL GLANDERS.
AB  - The bacillus of glanders may be so modified in virulence as to produce
      experimentally lesions differing widely in their histological features. The
      highly virulent culture causes primary necrosis and disintegration of the tissue
      followed by the invasion of the injured area by polymorphonuclear leucocytes. The
      bacilli of moderate virulence give rise to a primary lesion of an acute
      inflammatory nature in which the cells show no evidence of necrosis or
      disintegration. The attenuated bacilli produce primary tissue proliferation with
      the formation of epithelioid and giant cells. There is every grade of lesion
      between the acute exudative and the chronic proliferative depending upon the
      toxicity of the cultures. The glanders lesion whether exudative or proliferative
      is focal in character. The strong toxins of the glanders bacilli cause
      degeneration or necrosis of cells and exudation, while the dilute and weak toxins
      produce proliferation. The giant cell of glanders undoubtedly originates from the
      endothelial cell of the blood and lymph channels and is formed by division of the
      nucleus of the endothelial cell and not by cell fusion. Histologically the lesion
      of glanders resulting from the culture of a low degree of virulence is
      proliferative and is analogous to tuberculosis; the lesions are focal and bear an
      intimate relation to the glanders bacillus.

PMID- 19867097
TI  - A METHOD OF DIFFERENTIATING IN SECTIONS OF TISSUE BACTERIA DECOLORIZED BY GRAM'S
      STAIN.

PMID- 19867098
TI  - A STUDY OF THE EFFECT OF INTRAVENOUS INJECTIONS OF SOLUTIONS OF PANCREATIC
      TISSUE; WITH ESPECIAL REFERENCE TO THE CAUSE OF COLLAPSE IN ACUTE PANCREATITIS.
AB  - From these results it is permissible to draw the following conclusions which may
      be used to explain certain phenomena associated especially with the onset of
      acute pancreatitis. 1. The sudden marked collapse of acute pancreatitis has as
      its most important cause a toxin or toxins derived from broken down pancreatic
      tissue. This toxin or toxins seem to be most powerful in the stage of degradation
      just after the disappearance of the biuret reaction and are probably of the
      nature of aromatic and amino-compounds. 2. There are various contributing factors
      of toxic action as peptone and trypsin, but these are to be regarded as of
      secondary importance. 3. Mechanical irritation as stretching of the peritoneum
      and irritation of the caeliac plexus is a secondary cause. 4. The glycerine
      produced through the action of steapsin cannot be regarded as an important cause
      of collapse.

PMID- 19867100
TI  - THE TRANSFORMATION OF SERO-FIBRINOUS INTO PURULENT PLEURISY.

PMID- 19867099
TI  - EXPERIMENTAL PLEURISY-RESOLUTION OF A FIBRINOUS EXUDATE.
AB  - Fibrinous pleurisy produced by a sterile inflammatory irritant offers opportunity
      for study of the part taken by enzymes of leucocytes in the resolution of a
      fibrinous exudate. When turpentine is injected into the subcutaneous tissue of
      the dog, an abscess results, but when an equal quantity of turpentine is injected
      into the pleural cavity, there is abundant exudation of coagulable fluid and the
      serous surfaces are covered by a layer of fibrin. Accumulation of fluid which can
      be followed during life by percussion of the animal's chest reaches a maximum at
      the end of three days, and then gradually subsides, so that at the end of six
      days, in most instances, the cavity contains no fluid. Fibrin, though diminished
      in amount at the time when fluid has been absorbed, is still present, and
      gradually disappears; at the end of two or three weeks the cavity has returned to
      the normal, save for a few organized adhesions. Turpentine injected into the
      right pleural cavity may cause serofibrinous pleurisy on the left side; this
      inflammation may reach a maximum intensity at a time when pleurisy on the right
      side is subsiding. During the early stage of inflammation fibrinous exudate,
      freed from the serum by washing in salt solution, undergoes digestion when
      suspended in an alkaline (0.2 per cent. sodium carbonate) or in an acid medium
      (0.2 per cent. acetic acid). At the end of five days, at a time when fluid is
      disappearing from the pleural cavity, digestion fails to occur in an alkaline
      medium, but occurs with much activity in the presence of acid. During the first
      stage of the inflammatory reaction, when fluid is abundant and the fibrin which
      is present digests in alkali, thus indicating the presence of leucoprotease,
      polynuclear leucocytes are very numerous in the meshes of the fibrin. In the
      second stage, the exuded fibrin contains only one enzyme digesting in the
      presence of acid. At this time polynuclear leucocytes have disappeared and only
      mononuclear cells are embedded in the fibrin. Products of proteolytic digestion,
      namely, peptone and albumose, absent in the exuded fluid during the first day or
      two days of inflammation, are present after three days and are found in less
      quantity at a later period. The exuded fluid does not at any stage of the
      inflammatory reaction lose it spower to inhibit both enzymes contained in the
      leucocytes. The exudate remains alkaline throughout the period of inflammation,
      but its alkalinity is less than that of the blood and diminishes slightly with
      the progress of inflammation. Since the acids, which in vitro favor the action of
      the enzyme, present alone during the second stage of the inflammatory reaction,
      do not occur in the body, the possibility has suggested itself that carbon
      dioxide brings this enzyme into action. If carbon-dioxide is passed through
      normal salt solution in which strips of such fibrin are suspended, digestion is
      greatly hastened. The normal inhibition exerted by blood serum upon the enzyme is
      overcome by carbon-dioxide and in the presence of a small quantity of blood
      serum, carbon-dioxide causes greater enzymotic activity than in the presence of
      salt solution alone.

PMID- 19867101
TI  - THE DIFFERENTIATION OF STREPTOCOCCI BY MEANS OF FERMENTATIVE TESTS.
AB  - If we glance again at the classification proposed by Andrewes and Horder we are
      struck at once by the fact that no hard and fast differences in fermentative
      properties characterize the various groups, and that the authors prefer to have
      recourse to the most frequent habitat of the organisms and to chemical tests,
      rather than to confine themselves to the latter method alone. From what has been
      said earlier in this paper, it becomes clear at once that the results gained by
      these authors are not convincing, for in their work they have failed to use the
      most favorable medium for growth of the organisms. And thus it can hardly be
      doubted that different reactions might have been obtained, under the conditions
      adopted by us. How otherwise could the fact be explained that of thirty-four of
      their pneumococci only eight fermented inulin. We had a similar experience while
      using the plain broth which led us to reject it as an unfavorable medium.
      Further, all our pneumococci fermented lactose with great rapidity. Andrewes and
      Horder report that eight of their series left lactose unchanged. Taking our own
      tests into consideration we find that working with but a small number of
      carbohydrates we were able to find six different varieties of streptococci among
      only 33 pathogenic strains. Which of the various substances is to decide us in
      the grouping of the organisms? Would we not find even greater variations from the
      most common type (see No. 4 in table) if we were to extend our tests over a
      larger series of chemical agents? These questions are difficult to answer and
      only extended experimentation with a great many streptococci and many media will
      clear up the doubtful points. In concluding it may be stated: 1. Streptococci
      vary considerably in their ability to produce acid from various carbohydrates. 2.
      Chemical tests of this kind should be made only in the media which are most
      favorable for the growth of the organisms. 3. Our results gave us six groups of
      streptococci, when tested upon dextrose, levulose, galactose, maltose,
      saccharose, lactose, inulin, dextrin and mannite, viz.: Those fermenting (1) all;
      (2) all but mannite; (3) all but inulin; (4) all but inulin and mannite; (5) all
      but inulin and lactose; and (6) all but inulin, mannite and saccharose. 4. In
      view of the comparatively small number of streptococci employed we are hardly
      warranted in making a definite classification. Perhaps a larger series of tests
      upon the media employed will enable us to divide streptococci into distinct
      classes characterized by certain fixed fermentative properties.

PMID- 19867102
TI  - ON EXTRACELLULAR AND INTRACELLULAR VENOM ACTIVATORS OF THE BLOOD, WITH ESPECIAL
      REFERENCE TO LECITHIN AND FATTY ACIDS AND THEIR COMPOUNDS.
AB  - In normal serums of the majority of mammalian and avian blood there exists
      certain substances capable of activating venom haemolysin. They are extractable
      from serum by means of ether, and are capable of conferring upon the originally
      non-activating serum a power to activate venom, when mixed with the latter. The
      ethereal extract consists of fatty acids, neutral fats and possibly also some
      ether soluble organic soaps. The fatty acids and soaps, especially of the oleinic
      series, acquire certain characteristics of complements in general, when they are
      mixed with serum. They are inactive without the venom in the mixture; they are
      inactivable with calcium chloride; they exhibit a tendency to go off in activity
      with age; they are inactive or only weakly active at 0 degrees C., and they are
      extractable by ether. In testing the serum from which the ether soluble
      substances are removed, it is found that no venom activating property is left.
      Warm alcoholic extraction of such serum yields, however, a large quantity of
      lecithin. In the case of non-activating serums no venom activating fats appear in
      the ethereal extract. Lecithin exists in such serum in no less quantity than in
      the activating kind. The addition of oleinic acid or its soluble soaps to a non
      activating serum, in a ratio which corresponds to the percentage of fatty acids
      or soaps contained in some of the easily activating serums, will make the serum
      highly active in regard to venom. In normal serum of dog there exists, besides
      the group of activators already mentioned, another kind of venom activators which
      has been identified as a lecithin compound acting in the manner of free lecithin.
      A very sharp differentiation of the haemolysis produced by this activator and by
      the other groups of activators is obtained by means of calcium chloride, which is
      powerless against lecithin or lecithin compounds, but effective in removing the
      action of the latter. This lecithin containing proteid can be precipitated by
      half saturation with ammonium sulphate, but is perfectly soluble in water, and is
      not coagulated in neutral alkaline salt solutions upon boiling. Alcohol
      precipitates a proteid-like coagulum and extracts lecithin from it; ether does
      not extract lecithin from this compound. Non-activating serums do not contain any
      such lecithin compound. Lecithin contained in other serum proteids, mainly as
      lecithalbumin, and perhaps as contained in globulin, is not able to activate
      venom. This is true of all the serums with which I worked; it matters not whether
      these fractions (obtained with ammonium sulphate) belong to the most activating
      serum (dog) or to the non-activating serum (ox). The non-coagulable portion of
      all heated serum contains a venom activator of the nature of lecithin. This
      activator is contained in a non-coagulable proteid described by Howell which is
      identical with Chabrie's albumon. As there is no ether-extractable lecithin in
      this portion of the serum, the activating property of heated serum must be due to
      this proteid compound of lecithin. That this lecithin proteid does not pre-exist
      in normal serum but is produced by the action of high temperature is true of all
      serums except that of the dog. In venom activation we know now that lecithin
      becomes reactive with venom when it is transformed from other proteid compounds
      into the non-coagulable form, the albumon. Howell's view of the non-existence of
      the non-coagulable proteid in normal serum seems to receive a biological support
      from venom haemolysis. Ovovitellin derived from hen's egg is one of the best
      venom activators of the lecithin proteid type. The cause of venom susceptibility
      of various kinds of blood corpuscles does not depend upon the existence of
      lecithin in the corpuscles, but solely upon the amount of fatty acids, and
      perhaps, also, soaps and fats, contained in the corpuscles. The protection which
      calcium chloride gives against venom haemolysis is proof of the absence of
      lecithin activation. From the stroma of susceptible corpuscles fatty acids or
      some fats can be extracted with ether. After ethereal extraction the stroma
      becomes non-activating, while the extract contains fatty acids and some soaps or
      fats, which when added to venom-resistant corpuscles render the latter vulnerable
      to venom. The corpuscular solution of non-activating corpuscles does not contain
      enough fatty acids. The larger the amount of fatty acids and soaps in the
      corpuscles, the easier the cells undergo venom haemolysis. Lecithin exists in the
      strorna of all kinds of corpuscles, but in a form unavailable for venom
      activation. The somatic cytolytic processes caused by venom requires
      intracellular complements. The experiments performed on the cells of liver,
      kidney, testis and brain of the guinea-pig and rat indicate that the substances
      which act as complements are inactivable by calcium chloride.

PMID- 19867103
TI  - ON THE INFLUENCE OF THE REACTION AND OF DESICCATION UPON OPSONINS.
AB  - Opsonins reveal their maximum action in a medium of neutral reaction. No
      opsonization takes place in a serum which contains an amount of alkali
      corresponding to more than 1.6 c.c. of a 1/20 N. solution, or acid more than 0.5
      c.c. of this concentration per 1 c.c. of serum. Of several normal blood serums
      titrated (lacmoid used as indicator) the average alkalinity was found to be
      equivalent to about 0.8 c.c. of 1/20 N. solution. The opsonic index obtained in
      the native serums is not the expression of the action of the whole content of
      opsonins, but only so much as the degree of optimum of the reaction permits to
      come into action. Estimation of the opsonic power should, therefore, be made in a
      medium of neutral reaction and in diluted serum. All serums have their opsonic
      power increased by diminishing the native alkalinity. Opsonins whose activity is
      suspended by an unfavorable reaction become immediately active as soon as the
      reaction is brought back to the neutral point, unless the acid or alkali employed
      approaches the strength of 1 N., at which point the alteration becomes permanent.
      Treatment of a serum with alcohol robs it of its opsonic power. The opsonic power
      of serum remains unaltered upon desiccation at 23 degrees C. In the dry state
      opsonins are preserved for two years. The temperatures of 100 degrees , 120
      degrees , 135 degrees and 150 degrees C. do not destroy opsonins of the dried
      serum. Complements of serum are also siccostabile and are preservable in that
      state for several months. Dry heat of 135 degrees C. reduces but does not destroy
      the complementary power of the dried serum. The opsonins and complements of the
      dried serum regain their original thermolability when they are dissolved in a
      proper amount of water. Lastly, it may be emphasized that opsonins exhibit in
      their sensitiveness to reaction and resistance in the dry state to high
      temperatures certain properties characteristic of the ferments.

PMID- 19867105
TI  - THE EFFECT OF CERTAIN SURGICAL ANTISEPTICS AND THERAPEUTIC AGENTS ON PHAGOCYTOSIS
      : I. CARBOLIC ACID, MERCURIC CHLORIDE, BORIC ACID, QUININE HYDROCHLORIDE.

PMID- 19867104
TI  - SPIROCHAETA (TREPONEMA) PALLIDA AND SYPHILIS.

PMID- 19867107
TI  - OPSONINS OF INFLAMMATORY EXUDATES.

PMID- 19867106
TI  - A FURTHER CONTRIBUTION TO THE KNOWLEDGE OF THE OPSONINS.
AB  - 1. The determination of Wright's index of the opsonic content of the blood and
      other fluids of the body is open to serious and in part unavoidable errors and
      should be abandoned in its present form. 2. Conclusions based upon the
      determination of the opsonic content of the blood, according to Wright's method,
      are accordingly not uniformly reliable. 3. The percentage index is a valuable
      check on Wright's bacillary index, but likewise does not furnish an adequate idea
      of the opsonic content of the blood, unless carried out with progressive
      dilutions to the point of opsonic extinction. 4. The opsonins of normal blood
      serum are not specific. 5. The specificity of the opsonins in "immune" sera has
      not been satisfactorily established, but appears probable. 6. An opsonic
      immunity, in the sense of a continued high opsonic content of the blood does not
      exist. 7. In the blood and exudates of infected individuals substances may be
      present which exercise an inhibitory effect upon phagocytosis.

PMID- 19867108
TI  - EXPERIMENTAL LIVER NECROSIS; I. THE HEXON BASES.
AB  - 1. The liver of the dog in which necrosis has been produced by injection of
      haematoxic immune sera is characterized in the less marked forms by a storing up
      of nitrogen in the persisting living cells, while in the diffuse forms the total
      nitrogen content is but slightly above the normal. This last is to be explained
      by the great diminution in persisting liver substance which limits the power of
      nitrogen accumulation. 2. In all forms of necrosis there occurs an absolute
      increase of nitrogen precipitable by phosphotungstic acid (hexon bases) but the
      percentage increase, in relation to total nitrogen, diminishes in those forms
      (focal) in which the products of autolysis may be readily carried off by the
      blood stream and greatly increases in the diffuse form with large areas in which
      the circulation is seriously impaired. 3. Although the absolute amount of
      nitrogen representing arginin and histidin varies, a relative increase is evident
      when this fraction is compared with the total diamino-nitrogen. This increase
      corresponds to the degree of necrosis and attendant circulatory disturbance and
      indicates that in necrosis as opposed to degeneration (Wakeman) arginin is not
      split up by arginase. The lysin also bears a definite relation to the total hexon
      nitrogen. 4. The diamino-nitrogen of the normal liver after autolysis in vitro
      shows a slight variable increase over that of the unautolyzed, while the necrotic
      livers showed a decided decrease. 5. The diamino-acid nitrogen of normal horse
      liver is only about one half of that of the dog; the relative proportion of the
      bases is about the same. In necrotic livers with amyloid the diamino-nitrogen is
      markedly increased which is in accord with Neuberg's observations on the high
      hexon base content of amyloid.

PMID- 19867109
TI  - EXPERIMENTAL LIVER NECROSIS; II. ENZYMES.
AB  - 1. The presence of blood serum has a decided inhibitory effect on autolysis. Thus
      in the normal unwashed organs the non-coagulable nitrogen increase was 100 to 300
      per cent., while in the washed it amounted to 450 per cent. The washed necrotic
      livers showed an increase of from 600 to 850 per cent., while that of the
      unwashed necrotic was only slightly above the normal unwashed. 2. While the
      initial amount of non-coagulable nitrogen varies it is greater in those livers
      showing the more extensive forms of necrosis. The final amount of autolysis is
      also greatest in livers of this type. As regards the rate of autolysis fifty per
      cent. of the total occurs in the first day in the normal and in all types of
      lesions both washed and unwashed. The maximum is usually reached on the third day
      in the unwashed, while in the washed there is a continued increase to the eighth
      day. At this time in the necrotic livers about two to three times as much of the
      total nitrogen is in the form of non-coagulable nitrogen as in the normal. 3. In
      the necrotic tissue the initial controls show the content of monamino-acids, with
      one exception, to be practically doubled. In the washed necrotic the final amount
      is seventy per cent. of the total nitrogen against forty-six to fifty-seven per
      cent. in the washed normal. In all cases the monamino-acid nitrogen runs parallel
      to the nitrogen in non-coagulable form, but in relation to the total nitrogen it
      shows a greater increase in the washed than in the unwashed organs. 4. The
      ammonia production in the necrotic livers as shown by the partition experiments
      is greater than that in the normal and this increase corresponds to that of the
      non-coagulable nitrogen. In the experiments concerning the absolute production of
      ammonia in the presence of serum a greater amount was produced in the two and
      five hours' lesions than in the normal livers. On the other hand, the forty-eight
      hour diffuse necrosis equaled the normal and the focal fell below. 5. Arginase
      was obtained from normal but could not be isolated from necrotic livers. 6. No
      constant relation could be demonstrated between the anatomical lesion in the
      liver and the presence of leucin and tyrosin in the urine. Leucin was found
      occasionally in the urine, but none in the liver. On the other hand, tyrosin was
      constantly present in livers with diffuse but rarely in those with focal
      necrosis. In the instances of diffuse necrosis in which the liver and urine of
      the same animal were examined tyrosin was found in both. 7. The presence of large
      amounts of proteoses in the necrotic liver indicates that the elimination of
      these substances (colloidal nitrogen of Salkowski) under such circumstances may
      account for a part of the total nitrogen of the urine usually attributed to the
      monamino-acids.

PMID- 19867110
TI  - EXPERIMENTAL LIVER NECROSIS; III. NITROGENOUS METABOLISMS.
AB  - 1. In focal and diffuse necroses of the liver due to haemotoxic sera there occurs
      an increased elimination of total nitrogen with a corresponding augmented output
      of urea. The ammonia excretion becomes slightly diminished at first, but later
      rises somewhat above normal. The undetermined nitrogen is markedly increased. 2.
      In diffuse degeneration with no necrosis on the other hand only a slightly
      increased output of total nitrogen is evident. A rearrangement of the urea
      ammonia proportion occurs in that the ammonia excretion is augmented while the
      urea elimination is correspondingly diminished. The undetermined nitrogen rises
      but little. 3. In control experiments with normal serum no effect is produced. 4.
      These results would appear to indicate that in lesions characterized by uniform
      degeneration of the liver parenchyma, in contradistinction to necrosis, there
      occurs no increased nitrogen elimination but merely a disturbance of the urea
      forming function of the cell without the appearance in the urine of products of
      autolysis. On the other hand in necrosis, of even considerable extent, the total
      nitrogen is greatly augmented, as is also the rest-nitrogen; while the production
      of urea, on account of the persistence of normally functioning liver cells,
      remains relatively unchanged. This "factor of safety"(32) possessed by the liver
      is, we think, one of the most important results brought out in this investigation
      and must be given great weight in any consideration of the chemistry of hepatic
      disturbances.

PMID- 19867111
TI  - EXPERIMENTAL LIVER NECROSIS; IV. NUCLEIN METABOLISMS.
AB  - In necrosis of the liver of the dog produced by haemotoxic immune sera, the
      increased excretion of uric acid, purin bases and inorganic phosphorus pentoxide
      is the result of the hydrolysis of nuclear material occurring during the
      autolysis of the necrotic tissue.

PMID- 19867112
TI  - EXPERIMENTAL LIVER NECROSIS. V. THE FATS AND LIPOIDS.
AB  - 1. Changes which occur in the fat content of the liver of dogs receiving
      haemotoxic serum bear no relation to the degree of necrosis produced by this
      serum. 2. An increase in water content of the tissue seldom occurs, but where
      present is due to the nitrogenous autolysis rather than to the deposition of fat.
      3. The appearance of fat in the cell is not associated with a decomposition of
      the proteid component of the compound fats, but rather to a simple splitting off
      of the fatty radical. This is shown by the slight variations occurring in the
      percentage nitrogen of the fat-free substance. 4. The iodine equivalent
      diminishes as the fat content increases. This would indicate that in the fatty
      changes which occur, fats other than those containing oleate radicals make their
      appearance. 5. The ratio of phosphorus to nitrogen in the alcohol-chloroform
      extract remains practically constant in all degrees of necrosis. Hence the
      substances of the protagon and jecorin type hold the same relation to the
      lecithins during the autolysis as they do normally. 6. In a general way it may be
      said that the results obtained in the microchemical staining of the fats with
      Scharlach R agree with those found by chemical extraction methods.

PMID- 19867113
TI  - BIOLOGICAL RELATIONSHIPS OF DIPLOCOCCUS INTRACELLULARIS AND GONOCOCCUS.
AB  - The most marked differences, exclusive of pathogenic effects in man, between
      gonococcus and Diplococcus intracellulans are cultural ones, and consist chiefly
      in abundance of growth and choice of medium. Relatively larger doses of gonococci
      than of diplococci are required to kill young guinea-pigs, but the lesions are
      very similar in the two cases, and both organisms lose pathogenic power rapidly
      when cultivated artificially. Agglutinins, aggressins, protective power, and the
      amboceptors developed in the serum of immunized animals seem to be largely common
      to both diplococcus and gonococcus. Neither other Gram negative cocci nor
      Streptococcus pyogenes have any receptors in common with intracellularis and
      gonococcus.

PMID- 19867114
TI  - FURTHER INVESTIGATION UPON THE INFLUENCE OF ORGAN EXTRACTS OF COLD-BLOODED
      ANIMALS ON THE BLOOD PRESSURES.
AB  - 1. None of the extracts examined are very potent in small doses. A noticeable
      effect, however, is produced upon the blood pressure by the extract of fifteen
      milligrams of shark testis. 2. A small dose of a five per cent. shark testis
      extract seems to show more pressor action than a larger dose of the same
      solution. 3. The fall of blood-pressure is due to a vaso-dilation. 4. After
      repeated (seven or eight) injections of almost any extract, an injection of more
      of the same extract, or of another extract, which would be rather potent as a
      "first" injection, causes very little if any response from the blood-pressure. 5.
      Continued boiling of an extract destroys the pressor substance. 6. The depressor
      action is then very pronounced and especially prolonged. 7. The depressor
      substance will dialyze. 8. The pressor and depressor substances cannot be
      separated by dialysis, because in the repeated sterilizations the pressor
      substance disappears. 9. The pressor and depressor substances cannot be separated
      by absolute alcohol, as each seems to be soluble. The solubility is not, however,
      very great, at least in the cold. 10. It seems impossible to separate the pressor
      and depressor substances by means of a difference in solubility in cold
      physiological salt solution, since the depressor substance is even more soluble
      in that solution than the pressor. And yet the depressor substance is not nearly
      all removed by this means, even though it is allowed to stand for some time. 11.
      After cutting the vagi, the recovery from the effect of the depressor substance
      is much more rapid than with the vagi intact. The amount of fall of blood
      pressure is about equal in either case. 12. Extracts of the testis and pancreas
      of shark; of the testis and spleen of swordfish; and the spiral valve of dogfish
      show the presence of a pressor substance. 13. Extracts of the testis, spleen,
      pancreas and liver of shark; of the testis, liver, spleen and kidney of
      swordfish, and the spiral valve of dogfish show the presence of a depressor
      substance. 14. Extracts of shark ovary gave no result. I believe, however, that
      if sufficient of the parenchymatous tissue of the ovary had been obtained a
      result would have been given by this organ also.

PMID- 19867115
TI  - THE CHEMISTRY OF THE LIVER IN ACUTE YELLOW ATROPHY.
AB  - From the liver of a young man who died of typical, " idiopathic" acute yellow
      atrophy of the liver, after an illness of six weeks, there were isolated and
      identified the following amino acids: Histidin, lysin, tyrosin, leucin,
      glycocoll, alanin, prolin, glutaminic acid, aspartic acid. These were found free
      in extracts of the liver, and presumably represent products of the autolysis of
      liver cells, although the amount of soluble non-protein nitrogen present in the
      extracts was so large as to suggest that there must be some other source for
      these substances. Small quantities of free proteoses and peptones, and of xanthin
      and hypoxanthin, were also found in the extracts. In the insoluble proteins of
      the liver the proportion of diamino acids was decreased slightly as compared with
      normal livers. The proportion of protein phosphorus was increased, probably
      because of active regenerative proliferation, while the sulphur was normal in
      amount. Iron was increased because of the large quantity of blood in the liver
      and the hematogenous pigmentation of the liver cells. Gelatigenous material was
      increased both absolutely and relatively, because of the loss of parenchyma and
      the proliferation of the stroma. The proportion of water to solids was much
      increased, there having been a loss of over two-thirds of the entire
      parenchymatous elements of the liver. The amount of fat, lecithin and cholesterin
      was not far from that normal for the liver.

PMID- 19867116
TI  - ON THE CHEMISTRY AND STAINING PROPERTIES OF CERTAIN DERIVATIVES OF THE METHYLENE
      BLUE GROUP WHEN COMBINED WITH EOSIN.
AB  - 1. Eosinate of thionin gives very satisfactory staining for blood smears. It is
      easily prepared and dissolves readily in methylated spirits. 2. In the methods
      heretofore employed for making mixtures of eosin and methylene blue derivatives,
      the eosinates of methylene violet and methylene azure are present in very small
      quantities or are altogether absent. 3. Thionol and thionin are probably formed
      in methylene blue which has been long boiled with dilute alkalies and silver
      oxide. 4. Good stains of eosin and methylene blue derivatives can be obtained by
      a variety of manipulations. 5. Methylated spirits is more economical as a solvent
      for this stain and better adapted for the simple technique above described than
      is methyl alcohol. There is some evidence that the staining act is of a chemical
      nature.

PMID- 19867117
TI  - FEVER: ITS METABOLIC CHANGES.

PMID- 19867118
TI  - GENETICS OF SOMATIC MAMMALIAN CELLS : I. DEMONSTRATION OF THE EXISTENCE OF
      MUTANTS WITH DIFFERENT GROWTH REQUIREMENTS IN A HUMAN CANCER CELL STRAIN (HELA).
AB  - The parental HeLa cell population, a morphologically uniform, human cancer cell
      strain, grown for several years in tissue culture by procedures always involving
      massive inocula, has been shown to contain different mutant cell types. Two
      clonal lines have been isolated and established as reliable stock cultures. Both
      strains exhibit 100 per cent plating efficiency in high or low serum
      concentrations in the presence of a feeder system. In the absence of a feeder
      system and in low serum concentrations, the two strains are quantitatively
      differentiable: S3 still exhibits 100 per cent plating efficiency, while that of
      S1 lies in the neighborhood of zero. These differences have remained stable
      throughout 100 successive generations of growth of each strain including 2 single
      cell isolations. Application of these techniques to studies in the genetics of
      mammalian somatic cells and to specific cell-cell interactions has been
      indicated.

PMID- 19867119
TI  - THE INDUCED SUSCEPTIBILITY OF THE GUINEA-PIG TO THE TOXIC ACTION OF THE BLOOD
      SERUM OF THE HORSE.
AB  - Following the divisions before used, the results presented in the preceding pages
      may be briefly stated. I. The particular method of sensitization and the place
      where the test injection is made have an important bearing on the results
      obtained by various workers. Comparing the results obtained by the various
      methods, we may conclude that the incubation period of the hypersensitive
      reaction is not sharply limited, but that there is a progressive increase in
      sensitiveness from the sixth day, and presumably before that, extending over a
      period of several weeks. It seems very probable that the degree of
      hypersensitiveness attained where the sensitizing dose consists of a mixture of
      diphtheria toxin and serum is greater than when a single dose of the same small
      quantity of serum is given alone. II. Our early experiments, the first in this
      field, are in thorough agreement with those first reported by Otto, and shortly
      after him by Rosenau and Anderson. III. This hypersensitive reaction is
      transmissible from mother to offspring. The transmission is probably not equally
      effective in all cases, and individual young guinea-pigs probably vary greatly in
      the rate with which they lose their ability to react. As a result not all of the
      young of a hypersensitive mother react to a subcutaneous dose of five cubic
      centimeters of serum given when they are four or five weeks old. The reaction in
      the young animals differs quite markedly from that in those actively sensitized.
      These differences are such as to indicate that in the mother there is a
      considerable localization of the reaction in tissues and organs whose destruction
      does not cause sudden death. This local reaction is a protective factor and is
      not transmitted to the same degree as the factors involved in the fatal acute
      reaction. IV. The hypersensitive reaction to horse serum depends on the
      development of a special anti-body during the incubation period, which anti-body
      may be passively transferred to a fresh animal. If the dose of hypersensitive
      serum be sufficient, and the intoxicating injection be given directly into the
      circulation, this passive hypersensitiveness may be enough so that the animal
      will die when tested. There is also in the serum of hypersensitive guinea-pigs an
      uneliminated horse serum element or "rest," which is distinct from this antibody,
      and probably without influence on the course of the acute reaction. V. The anti
      body on which the hypersensitive reaction depends may be entirely neutralized by
      horse serum without causing symptoms. The gradual introduction of increasing
      doses over a total period of twenty-four hours suffices for this. The animal is
      then, properly speaking, neither immune nor refractory, but is essentially in the
      condition of a normal animal which has recently had a large dose of horse serum.
      This rapid neutralization is made possible by the great binding power which the
      subcutaneous and other relatively unimportant tissues have for the toxic element
      of the serum. The so-called "Phenomenon of Arthus" is probably the same reaction
      for the rabbit that we have here dealt with in the guinea-pig. The fact that the
      manifestation is more prominently a local one depends on racial differences. I
      have encountered cases in the guinea-pig in which the conditions in the rabbit
      are closely simulated.

PMID- 19867120
TI  - SERUM TREATMENT OF EPIDEMIC CEREBRO-SPINAL MENINGITIS.

PMID- 19867121
TI  - STOMACH FEEDING IN MICE.

PMID- 19867123
TI  - THE TRANSPLANTATION OF HUMAN CARCINOMATOUS MATERIAL INTO LOWER ANIMALS.

PMID- 19867122
TI  - ON THE INHIBITORY INFLUENCE OF EOSIN UPON SPORULATION.
AB  - Sporulation of B. anthracis, B. subtilis, B. cereus, B. ruminatus, B.
      mesentericus, B. anthracoides and B. megatherium does not take place in an agar
      medium containing eosin "Gelb" in a concentration exceeding 0.5 per cent. In a
      concentration of 0.1 per cent. most of these bacteria fail to produce spores. The
      greatest sensitiveness is shown by B. cereus and B. mesentericus. In a bouillon
      medium sporulation is likewise inhibited by eosin, but after a longer time-seven
      weeks or more-sporulation still occurs where the concentration of the dye equals
      one-tenth per cent. Sporulation of B. tetani, B. anthracis symptomaticus, B.
      botulismus, B. oedema maligni, B. enteritidis sporogenes, and B. putrificus does
      not take place in a medium containing eosin "Gelb" in concentrations exceeding
      0.03 per cent. With these organisms, no difference was noted in the final effect,
      depending on the medium employed. No permanent loss of power to produce spores
      ensues with the bacteria tested even after long sojourn in the eosinized media.
      It may be stated that on the whole the inhibitory action of eosin was more
      pronounced upon the anaerobic than upon the aerobic species of bacteria employed
      in these experiments.

PMID- 19867124
TI  - RIGOR MORTIS AND THE INFLUENCE OF CALCIUM AND MAGNESIUM SALTS UPON ITS
      DEVELOPMENT.
AB  - Calcium salts hasten and magnesium salts retard the development of rigor mortis,
      that is, when these salts are administered subcutaneously or intravenously. When
      injected intra-arterially, concentrated solutions of both kinds of salts cause
      nearly an immediate onset of a strong stiffness of the muscles which is
      apparently a contraction, brought on by a stimulation caused by these salts and
      due to osmosis. This contraction, if strong, passes over without a relaxation
      into a real rigor. This form of rigor may be classed as work-rigor
      (Arbeitsstarre). In animals, at least in frogs, with intact cords, the early
      contraction and the following rigor are stronger than in animals with destroyed
      cord. If M/8 solutions-nearly equimolecular to "physiological" solutions of
      sodium chloride-are used, even when injected intra-arterially, calcium salts
      hasten and magnesium salts retard the onset of rigor. The hastening and
      retardation in this case as well as in the cases of subcutaneous and intravenous
      injections, are ion effects and essentially due to the cations, calcium and
      magnesium. In the rigor hastened by calcium the effects of the extensor muscles
      mostly prevail; in the rigor following magnesium injection, on the other hand,
      either the flexor muscles prevail or the muscles become stiff in the original
      position of the animal at death. There seems to be no difference in the degree of
      stiffness in the final rigor, only the onset and development of the rigor is
      hastened in the case of the one salt and retarded in the other. Calcium hastens
      also the development of heat rigor. No positive facts were obtained with regard
      to the effect of magnesium upon heat vigor. Calcium also hastens and magnesium
      retards the onset of rigor in the left ventricle of the heart. No definite data
      were gathered with regard to the effects of these salts upon the right ventricle.

PMID- 19867125
TI  - A FATAL ANAEMIA WITH ENORMOUS NUMBERS OF CIRCULATING PHAGOCYTES.

PMID- 19867126
TI  - TRANSPLANTATION IN MASS OF THE KIDNEYS.
AB  - Among so many etiological factors, it is impossible to discriminate which are
      responsible for the complications which took place in our experiments. An attempt
      to explain the occurrence of nephritis, cedema or calcification of the arterial
      system, for instance, will not be made, but the technique of the operations will
      be modified in order to suppress as much as possible the causes which may
      originate these secondary changes. The purpose of this article was not to analyze
      minutely the physiological or pathological character of the functions of
      transplanted kidneys, but merely to ascertain whether these functions are
      efficiently reestablished. It is to be concluded that an animal which has
      undergone a double nephrectomy and the grafting of both kidneys from another
      animal can secrete almost normal urine with his new organs, and live in good
      health at least for a few weeks. This demonstrates that it is possible to
      reestablish efficiently the functions of transplanted kidneys.

PMID- 19867127
TI  - A DETAILED STUDY OF THE CHANGES OCCURRING IN THE PHYSIOLOGICAL DEGENERATION OF
      ACTINOSPHAERIUM EICHORNI.

PMID- 19867128
TI  - THE OPHTHALMO-TUBERCULIN REACTION IN CATTLE.
AB  - THE CONCLUSIONS TO BE DEDUCED FROM THIS BRIEF SERIES OF EXPERIMENTS ARE AS
      FOLLOWS: 1. The ophthalmo-tuberculin reaction is of some value for diagnosis of
      tuberculosis in cattle. A characteristic conjunctivitis with fibrinous exudation
      coming on from six to eight hours, reaching a maximum in from sixteen to twenty
      four hours and disappearing in forty-eight hours, is noted in tubercular animals.
      2. The reaction is more pronounced in those animals which have not been recently
      tested with tuberculin. With this reaction as with the usual tuberculin test one
      injection and reaction probably inhibit a second reaction during a period from
      six weeks to a year. The ordinary tuberculin test does not seem to interfere to
      any great extent with the ophthalmo-tuberculin test at least within four weeks.
      Class B, though recently tested, showed the reaction, although not to the extent
      of Class A, which was tested some time ago. The tuberculin test occasionally
      prevents absolutely a second reaction, and usually no second reaction occurs
      within six weeks to a year, as before stated. 3. In cattle recently tested with
      tuberculin by the subcutaneous method the ophthalmo-tuberculin reaction is only
      slightly reduced in its intensity. The ophthalmic test may possibly serve as a
      means of diagnosis of tuberculosis in cattle which have been tested with
      tuberculin by the ordinary method and will not react a second time, or where
      tuberculin has been injected into cattle in order that they may clear a second
      test. Another possibility must not be overlooked in this connection. It is well
      known that animals which have a slight tubercular infection often show a very
      marked and typical reaction to the tuberculin test as it is usually made, and
      those animals which show themselves clinically to be in the advanced stages of
      tuberculosis often show only a very slight reaction. The animals in Class B are
      in the advanced stages of tuberculosis and this fact might perhaps account for
      the lower intensity of the reaction. The exact cause of the lower reaction in
      these cattle can only be determined by further experimentation. 4. No
      constitutional disturbance being noticed in any of the cattle tested, that is, no
      rise in temperature, loss of appetite or falling off in the production of milk,
      it is evident that the instillation of tuberculin into the eye does not produce
      the general reaction which attends in some cases the subcutaneous injection of
      tuberculin, and is therefore decidedly advantageous. The exudate disappears and
      leaves the eye perfectly normal in forty-eight hours after injection. 5. If the
      ophthalmo-tuberculin test proves as efficacious as the foregoing experiments seem
      to indicate we have in it a comparatively rapid and easy means of diagnosing
      tuberculosis in cattle. Such being the case the method cannot fail to come into
      general use superseding the present laborious method of applying the test. Cattle
      can be injected and then inspected sixteen to twenty-four hours afterward. There
      are many problems in connection with the reaction which must necessarily be
      studied. The following are a few of the propositions: 1. Is it possible to tell
      by the reaction how far the tubercular process has progressed in the body? 2. Is
      there any relationship between the intensity of the reaction and the number and
      severity of the tubercular lesions? 3. Will the test prove to be more accurate
      than the ordinary tuberculin test which is said to reveal all but four per cent.
      of the cases ? 4. Will the test reveal tuberculosis after a subcutaneous
      tuberculin injection? 5. Will animals react a second time if the first tuberculin
      is placed in the eye and the second given by the ordinary subcutaneous method and
      conversely? These and many more points must be thoroughly investigated before the
      efficiency of the test is proven. The opththalmo-tuberculin test will be repeated
      on other cattle, and also on the cattle used in these experiments. Experiments
      are being made to determine the efficiency of the cutaneous tuberculin reaction
      in cattle. We wish in this paper to give only the preliminary findings.

PMID- 19867129
TI  - AN INQUIRY INTO SOME MECHANICAL FACTORS IN THE PRODUCTION OF LYMPHOCYTOSIS.
AB  - 1. The lymph of the thoracic duct furnishes to the blood a larger proportion than
      is usually supposed of the lymphocytes in circulation. Gross variations in its
      output of such cells must affect very considerably the blood picture. 2. The
      quantity of lymphocytes supplied through the thoracic duct of the healthy dog
      remains practically constant from hour to hour, if the physiological conditions
      are not notably changed. Transient change in physiological conditions may alter
      the output of cells, but with the disappearance of this change the output tends
      to resume its previous rate. These facts indicate that the tissues producing
      lymphocytes are "set" at a rate of activity definite in the individual. 3.
      Muscular activity (struggle) produces a prompt increase in the output of
      lymphocytes through the thoracic duct. (a) This is assured by the presence of an
      increased number of cells per cubic millimeter of lymph, combined with an
      increase in the amount of lymph voided. (b) The lymphocyte-output may be tripled
      or quadrupled during a long-continued struggle. (c) Following prolonged struggle
      the output of lymphocytes is for a short time less than previous to the exertion.
      4. The increased lymph-flow caused by a lymphagogue of the second class (glucose)
      brings with it increased output of lymphocytes through the thoracic duct. (a) The
      individual cubic millimeters of lymph are often poor in cells, during the rapid
      lymph-flow, yet the total number of elements transported is large. (b) The
      results with glucose support the theory of Ehrlich, that a rapidly appearing
      lymphocytosis may be produced through the flushing effect of increased lymph
      flow. 5. A comparison of the effects of struggle with those of glucose
      demonstrates that in the former some factor besides increase in lymph-flow per se
      (Ehrlich) works to cause the large output of lymphocytes. The nature of this
      factor has not yet been determined. 6. The variations caused by muscular exertion
      and by increased lymph-flow in the number of lymphocytes coursing through the
      thoracic duct are so pronounced as to suggest that the total number of
      lymphocytes in circulation must be considerably influenced by them. Clinical
      findings by other observers indicate that this is true; and the clinical findings
      themselves become much simpler of interpretation. 7. The results in general prove
      the existence, reserved from circulation, of a large fund of lymphocytes, which
      is quickly yielded to the blood under certain physiological conditions.

PMID- 19867130
TI  - CONCERNING THE RELATION OF THE COAGULATION TIME OF THE BLOOD TO THROMBOSIS IN
      PHLEBITIS.
AB  - Positive results have been obtained in but a single set of experiments, namely
      those in which turpentine was employed. In so far as the results of this
      preliminary study go, one is led to the conclusion that thrombosis is most
      readily induced when active inflammatory lesions exist in the blood vessels,
      associated, probably in most instances, with secondary degenerative changes.
      Purely mechanical lesions are much less apt to be productive of conditions
      favorable to thrombosis as a sequence of phlebitis. Marked artificial increase or
      decrease in the coagulation time of the blood by the use of calcium lactate or
      citric acid, does not render animals abnormally prone to thrombosis incited by
      changes other than inflammatory. When true phlebitis exists, thrombosis is apt to
      be more extensive and less readily resolved, when the coagulation point of the
      blood has been shortened by the use of calcium lactate, and it is less extensive
      and more quickly absorbed when the coagulation time has been increased by the
      administration of citric acid. Experiments as yet incomplete appear to suggest
      that the increasing in rapidity or slowing of the general circulatory stream has
      but little bearing on the production of thrombosis in phlebitis, much less,
      indeed, than clinical and anatomical observations have generally led us to think.
      We have also been led to suspect that the presence or absence of anastomoses of
      abundant degree is largely concerned as a factor in determining the location and
      extent of thrombosis in phlebitis.

PMID- 19867131
TI  - CALCIFICATION OF THE ARTERIAL SYSTEM IN A CAT WITH TRANSPLANTED KIDNEYS.

PMID- 19867132
TI  - THE SO-CALLED RHYTHMS OF GROWTH-ENERGY IN MOUSE CANCER.
AB  - IN CONCLUSION WE MAY SUMMARIZE THE ABOVE BIOLOGICAL OBSERVATIONS IN A SERIES OF
      THESES AS FOLLOWS: 1. Cancer cells differ from other epithelial cells in respect
      to: (a) Size relations of nucleus and cell body; (b) power of indefinitely
      continued division. 2. Cancer cells differ from embryonic cells in absence of:
      (a) power of differentiation; (b) power of coordination of parts to whole; (c)
      power of self-regulation and limit of growth. 3. The continued development of the
      cancer cells is subject to the following factors: (a) the inherent potential of
      division of the cancer cells. (b) The natural resistance of the inoculated
      animals. The latter factor is usually regarded as the index of malignancy of a
      tumor and is based upon the percentage of takes together with the period required
      to kill the mice. Our experiments, however, show that the percentage of takes is
      independent of the time factor, and indicate the presence of a third factor which
      may be described as (c) the potential of "infectivity" of the cancer cells. 4.
      The potential of infectivity of cancer cells is characterized by more or less
      regular rhythms; these must be distinguished from rhythms of growth energy of the
      cancer cells which in all probability occur within the individual mouse. Without
      the division energy of the cancer cell this infectivity is inoperative, hence it
      follows that the cause of the infectivity lies within the cancer cell or is
      constantly associated with it. 5. Cancer cells differ from epithelial cells by
      virtue of this potential of infectivity combined with that of division energy.
      There is reason to believe that the latter is due to the action of stimuli and
      not to the liberation of a restrained growth power of embryonic tissue. There is
      reason to doubt that an initial and discontinued stimulus is responsible for
      these attributes of the cancer cells. Certain benign tumors, or vegetable galls,
      may be due to the action of such initial stimuli, but in them there is no
      infectivity. Embryonic tumors, due to embryonic cells, have a high power of
      differentiation combined with their division energy, but there is no infectivity.
      Infectivity distinguishes all cancerous growths from normal epithelium and from
      benign tumors or teratomata. 6. The rhythms of infectivity of cancer cells,
      erroneously regarded as rhythms of growth energy by Bashford, Murray and Boyen,
      appearing as they do in successive batches of mice which we may legitimately
      assume to have like powers of resistance, must have their cause in the cancer
      cells themselves. These cells, therefore, must be equivalent to parasites, or
      else parasites are contained within or associated with them. 7. Upon any other
      hypothesis it is difficult to conceive of cells creating a continual stimulus to
      their own growth energy, and it is still more difficult to explain the rhythms of
      infectivity. 8. Many lines of evidence point to the presence of some possible
      organism within the cancer cell; some organism which, acting as does
      Plasmodiophora brassicae within vegetable cells, underlies the infectivity of
      cancer cells and provides the stimulus for their continued proliferation. Upon
      such an assumption the numerous cases of cage infection find their explanation.
      9. The various inclusions of the cancer cell which have been described as
      organisms have been disproved; yet the analogy of club root and the many filter
      experiments show that the cause of infection may lie within the cancer cell. It
      is conceivable that, like the yellow fever organism, such an incitant may be in
      the protoplasm and beyond our powers with the microscope to locate. 10. The
      spirochaetes which we have found in mouse cancer may have something to do with
      this infectivity of cancer cells. They may be useful in preparing the "soil" in
      new mouse hosts and making it susceptible to cell growth; or they may have
      intracellular stages in their life history which are too minute to be seen. The
      rhythms of infectivity, finally, may be an expression of the vitality of these
      spirochaetes or of the hypothetical ultra-microscopical organisms accompanying
      cancer cells.

PMID- 19867133
TI  - A CONTRIBUTION TO THE PATHOLOGY OF MYASTHENIA GRAVIS. REPORT OF A CASE WITH
      UNUSUAL FORM OF THYMIC TUMOR.

PMID- 19867134
TI  - THE EFFECT OF PILOCARPINE ON THE OUTPUT OF LYMPHOCYTES THROUGH THE THORACIC DUCT.
AB  - The intravenous injection of pilocarpine nitrate causes in the dog a rapid and
      considerable increase in the output of lymphocytes through the thoracic duct. The
      corresponding lymphocytosis induced by the drug in the blood of this animal is
      not profound, and increased cell-output with the lymph will explain a large part
      if not all of it. Quickened lymph-flow and dyspnoeic breathing are accessory in
      the production of the large cell-output with the lymph, but it is mainly
      dependent on some undetermined element. The evidence points to the mechanical
      nature of this element. It is probably to be sought in direct pressure from
      contraction of smooth muscle, as suggested by Harvey, but his observation that
      atropine prevents the appearance of a lymphocytosis after pilocarpine cannot be
      quoted in proof because atropine much slows the lymph-flow, and thus decreases
      cell-output. These findings are in accord with the theory that makes mechanical
      factors responsible for rapidly appearing lymphocytosis. They show that there are
      more such factors than has been supposed. Especially do they indicate that the
      contribution of cells through the thoracic duct may be important in the
      production of lymphocytosis, and is not, as is often asserted, subsidiary to
      direct migration into the blood of cells from spleen, bone-marrow and the lymph
      glands.

PMID- 19867135
TI  - THE ENZYMES OF FIBRIN.

PMID- 19867137
TI  - ANGEIOMATA IN VALVES OF HEART OF A NEWLY BORN CHILD.

PMID- 19867136
TI  - BONE FORMATION IN SCLEROTIC ARTERIES.

PMID- 19867138
TI  - STUDIES IN RESUSCITATION: I. THE GENERAL CONDITIONS AFFECTING RESUSCITATION, AND
      THE RESUSCITATION OF THE BLOOD AND OF THE HEART.
AB  - OUR RESULTS MAY BE BRIEFLY SUMMARIZED: 1. Blood, when defibrinated, soon loses
      its power to maintain the activity of the higher nervous centers, and its
      nutritive properties for all tissues quickly diminish. 2. Artificial fluids, as a
      substitute for blood, are not satisfactory. 3. The proper oxygenation of the
      blood is an indispensable adjunct in the resuscitation of an animal. 4. The heart
      usually continues to beat for some minutes after it ceases to affect a mercury
      manometer, and resuscitation of it within this period by extra-thoracic massage
      and artificial respiration is sometimes successful. 5. Resuscitation of the heart
      by direct massage is the most certain method at our command. 6. A proper blood
      pressure is an indispensable condition for the continued normal activity of the
      heart. 7. Anaesthetics, hemorrhage and induced currents applied to the heart
      render resuscitation more difficult than asphyxia alone.

PMID- 19867139
TI  - THE EFFECT OF INJECTED LEUCOCYTES UPON THE DEVELOPMENT OF A TUBERCULOUS LESION.

PMID- 19867140
TI  - THE PATHOLOGICAL ANATOMY OF HYDRAZINE POISONING.

PMID- 19867141
TI  - MELANOMA OF VATER'S DIVERTICULUM AND LOWER PORTION OF COMMON BILE DUCT CAUSING
      COMPLETE OBSTRUCTION.

PMID- 19867142
TI  - A BIOLOGICAL STUDY OF THE CEREBRO-SPINAL FLUID IN ANTERIOR POLIOMYELITIS.

PMID- 19867143
TI  - THE PULSE PRESSURE AS AN INDEX OF THE SYSTOLIC OUTPUT.
AB  - ON THE BASIS OF THESE FACTS WE FEEL JUSTIFIED IN MAKING THE FOLLOWING ASSERTION:
      Under normal conditions and during various procedures (namely, stimulation of the
      vagus centrally and peripherally, of the saphenus nerve centrally, and of the
      annulus Vieussentis, intravenous transfusion of 0.7 per cent. sodium chloride
      solution, intra-arterial transfusion of strong carbonate, bleeding and asphyxia)
      the pulse pressure is a reliable index of the systolic output.

PMID- 19867144
TI  - STUDIES IN RESUSCITATION: IV. THE RETURN OF FUNCTION IN THE CENTRAL NERVOUS
      SYSTEM AFTER TEMPORARY CEREBRAL ANAEMIA.
AB  - The experiments on cerebral anaemia have enabled us to duplicate, by an entirely
      different method, many of the results obtained by anatomical division or removal
      of parts of the central nervous system. In some respects the method of anaemia
      permits of greater precision than the method of division or excision, and avoids,
      in great measure, the disturbances due to the wound and to the hemorrhage caused
      by the latter method. The method of general anaemia, as Couty pointed out long
      ago, leaves something to be desired in the matter of exact localization, but this
      objection may be met, in some degree at least, by appropriate methods of
      investigation. It is desirable that the results obtained by the method of section
      should be duplicated by some other method in order to eliminate as much as
      possible the effects due to the irritation produced by the anatomical lesion. Our
      results show, as we believe, that, of the bulbar mechanisms studied, the
      respiratory is the most automatic, the vasomotor in part automatic, and the
      cardiac like the swallowing mechanism, almost wholly dependent upon afferent
      impulses for the arousal and discharge of its normal activity. The eye reflexes
      return during the resuscitation period in the animals in which the cerebral
      anaemia has not been too prolonged. The motor cortex loses its excitability
      during anaemia, but may regain it after the reestablishment of the circulation.
      The pilomotor mechanism is disturbed during the spasms which occur at a certain
      stage in the resuscitation. The temperature falls during the occlusion period,
      but rises again, often to far above normal, in the days following the anaemia. So
      many disturbing factors, such as the violent muscular contractions during spasms,
      enter into the problem that it is impossible to say that there is an actual
      disturbance of the temperature regulating mechanism although we are inclined to
      believe that this is the case. All the senses return, following cerebral anaemia,
      but sight and hearing may afterwards fail without causing the death of the
      animal. The mental processes may return without any apparent deficiency, if the
      period of anaemia has been short. After longer occlusion, apparent insanity has
      been seen, and in one case, apparent total loss of mental processes occurred. The
      reflex excitability of the cord returns rather early in the resuscitation period.
      Reflexes from the anterior part of the cord first involve muscles on the same
      side as the stimulus, and later cross to involve muscles of the opposite side.
      The spinal cord sometimes falls into much the same condition as that following
      spinal transection, and the scratch reflex appears. Spinal transection, when
      these reflexes have appeared, does not produce shock. Practically all phenomena
      of spinal shock may be reproduced without section of the cord. We conclude,
      therefore, that spinal shock is due more to the cutting off of the reflex
      pathways through the higher centers of the nervous system than to the stimulation
      of inhibitory fibers by the anaemia.

PMID- 19867145
TI  - THE RATIO BETWEEN THE HEART-WEIGHT AND BODY-WEIGHT IN VARIOUS ANIMALS.

PMID- 19867146
TI  - THE PRODUCTION OF AGGLUTININS IN THE ANIMAL BODY BY THE INOCULATION OF SUBSTANCES
      OTHER THAN PRODUCTS OF BACTERIAL ORIGIN.

PMID- 19867147
TI  - SOME DIFFERENTIAL COUNTS OF THE CELLS IN THE LYMPH OF THE DOG: THEIR BEARING ON
      PROBLEMS IN HAEMATOLOGY.

PMID- 19867148
TI  - OBSTRUCTIVE HYDROCEPHALUS FOLLOWING CEREBROSPINAL MENINGITIS, WITH
      INTRAVENTRICULAR INJECTION OF ANTIMENINGITIS SERUM (FLEXNER).

PMID- 19867149
TI  - ON GLYCOTHIONIC ACID.

PMID- 19867150
TI  - THE HUMAN SPLEEN AS AN HAEMATOPLASTIC ORGAN, AS EXEMPLIFIED IN A CASE OF
      SPLENOMEGALY WITH SCLEROSIS OF THE BONE-MARROW.
AB  - 1. The nodules found in the spleen are islands of active haematoplastic tissue.
      2. The bone-marrow, at least in the case which has been described, has been the
      primary focus of disease; some toxin has probably produced a chronic inflammatory
      change. 3. The bone-marrow, owing to its enormous sclerosis, has lost its
      haemopoetic powers totally or to a marked degree and the spleen has reverted to
      its foetal power to form blood.

PMID- 19867151
TI  - THE RESULTS OF THE APPLICATION OF SPECIAL HISTOLOGICAL METHODS TO THE STUDY OF
      TUMORS.

PMID- 19867152
TI  - FURTHER STUDIES ON THE OPHTHALMO-TUBERCULIN REACTION IN CATTLE.
AB  - Our conclusions differ in a few points from those of our first work on this
      subject. We are able to sum up our observations in this series of experiments as
      follows: 1. The ophthalmo-tuberculin test is of limited value in the diagnosis of
      tuberculosis in cattle. In some cases the reaction is very slight (hyperaemia).
      In others more pronounced congestion with profuse exudates are noted. Accuracy of
      observation is important. We are inclined to rely primarily on the results of the
      first instillation of tuberculin. Second instillations in a few instances elicit
      reaction in non-tubercular animals. 2. In the majority of animals tested the
      reaction increased in its intensity with each subsequent instillation of
      tuberculin. This fact indicates the development of a local hypersusceptibility or
      anaphylaxis associated with a partial immunity; von Pirquet calls this condition
      "allergie" (9). 3. It is possible in some cases to create a condition of
      "allergie" in healthy cattle, when spaced instillations of tuberculin are made.
      It is evident, therefore, that the result of the first instillation of tuberculin
      should be made the only basis of diagnosis. Rosenau and Anderson (II) have
      recently called attention to this point in regard to the human subject. 4. When
      repeated instillations of tuberculin are made on the conjunctiva at short
      intervals (twenty-four hours, etc.) a local immunity results (No. 3D et al.). If
      the instillations are separated two weeks or more anaphylaxis results. 5. We,
      therefore, hold that if tuberculin (0.1 cubic centimeter) is carefully instilled
      into the conjunctival sac and if careful comparison of the instilled eye with the
      opposite eye shows that a reaction of varying intensity results in from ten to
      twelve hours after the first instillation, a tubercular lesion is present. 6. In
      our first report (7) we were inclined to believe that subcutaneous tubercular
      injection given previous to the ocular test would slightly inhibit it. We have
      since become convinced that this is true only to a limited extent, and that in
      some cases the ophthalmo-reaction is exaggerated by a subcutaneous injection of
      tuberculin. 7. The primary ophthalmo-tuberculin reaction is in direct proportion
      to the extent of the tubercular processes in the body. The more extensive the
      tubercular processes, the more anaphylactic the animal is. This is in direct
      variance with the condition in the usual subcutaneous tuberculin test. (See
      Necropsy Report.) 8. We are inclined to believe that the ophthalmo-tuberculin
      test will reveal tuberculosis at as early a state as the usual subcutaneous test.
      9. The ophthalmo-reaction is of no value in determining whether vaccinated cattle
      are actively tubercular or not, or in demonstrating any hypersusceptibility in
      the offspring of tubercular cattle. 10. The cutaneous test from our brief series
      of experiments does not seem to be as accurate as the ophthalmic test. This
      conclusion has been reached by several investigators.

PMID- 19867153
TI  - FURTHER OBSERVATIONS ON ANAPHYLAXIS TO HORSE SERUM.

PMID- 19867154
TI  - A STUDY OF THE PROTEOLYTIC FERMENTS OF THE LARGE LYMPHOCYTES IN A CASE OF ACUTE
      LEUKAEMIA.
AB  - The leucocytes of the blood of normal individuals and of patients showing a
      marked polymorphonuclear leucocytosis contain enzymes capable of digesting
      coagulated blood serum in neutral, alkaline or acid solutions. The cells in pus
      that is composed principally of polymorphonuclear leucocytes and the leucocytes
      of the circulating blood in myelogeneous leukaemia contain similar proteolytic
      enzymes, which act best when the reaction is alkaline. The leucocytes of the
      circulating blood and of the enlarged lymph nodes from a case of large cell,
      acute, lymphatic leukaemia contain proteolytic enzymes that act qualitatively in
      much the same way as the leucocytes of pus and as the white corpuscles of the
      blood in myelogenous leukaemia. These large lymphocytes in acute lymphatic
      leukaemia can be differentiated biologically from the small lymphocytes in
      chronic lymphatic leukaemia which possess no proteolytic enzymes, and from the
      large endothelioid cells of the hyperplastic lymph glands which are proteolytic
      only in the presence of acid. These results seem to show that the large cells of
      the so-called acute lymphatic leukaemia are not true lymphocytes, but are nearly
      related to the granular myelocytes and should probably be considered as the
      forerunners to these cells.

PMID- 19867155
TI  - THE INFLUENCE OF THE REDUCTION OF KIDNEY SUBSTANCE UPON NITROGENOUS METABOLISM.
AB  - 1. The removal of one half, two thirds and sometimes three quarters of the kidney
      substance in the dog causes no change in the general nitrogenous metabolism as
      determined by estimations of the total nitrogen, urea and ammonia elimination by
      the urine. 2. The removal of larger amounts, and sometimes of three quarters of
      the substance, leads to the metabolism condition of starvation. This, however, is
      apparently the result of the gastro-intestinal disturbance constantly associated
      with extensive kidney reduction and not of a disturbance of general nitrogenous
      metabolism. 3. The determination of the amount of faecal nitrogen indicates that
      the gastro-intestinal disturbance is not due to diminished absorption; and except
      in one instance there was no evidence of its being due to an increased
      elimination of nitrogenous substances into the intestine. 4. These experiments do
      not support the theory that the kidney furnishes an internal secretion having an
      important influence on general nitrogenous metabolism. At least, if such a
      function exists, it is not disturbed by the removal of three quarters of the
      kidney substance. 5. The metabolism in excessive kidney reduction is that of
      inanition dependent on gastro-intestinal disturbances presumably due to faulty
      chemical correlation. In this connection further knowledge concerning the
      elimination into the intestine of toxic substances is desirable.

PMID- 19867156
TI  - ENZYMES OF TUBERCULOUS TISSUE.
AB  - Epithelioid cells which form the chief element of tuberculous tissue contain an
      enzyme which causes active digestion of proteid in an approximately neutral or in
      a weakly acid medium, but is inactive in the presence of weak alkali. This enzyme
      resembles that which occurs in the large mononuclear cells of an inflammatory
      exudate and is more active than the similar enzyme of parenchymatons organs such
      as the liver. The enzyme which digests in the presence of acid exhibits greatest
      activity at a time when caseation is beginning. With advance of caseation its
      activity diminishes so that tissue which has undergone almost complete caseation
      exhibits trivial evidence of the presence of enzyme. It is probable that complete
      caseation is followed by total disappearance of enzymes. Tuberculous tissue
      contains an enzyme capable of digesting proteid in the presence of alkali
      (leucoprotease) only during the early stages of its development. This enzyme,
      present at a time when the tissue contains numerous polynuclear leucocytes,
      quickly disappears so that when enzyme digesting in acid is still active,
      leucoprotease has disappeared. The serum of a tuberculous pleural exudate
      obtained by intrapleural inoculation with tubercle bacilli causes slight
      inhibition of the mixture of enzymes contained in tuberculous tissue shortly
      after inoculation. The serum of blood causes complete inhibition of the enzymes
      contained in the same tuberculous tissue. Analysis of this difference indicates
      that the exuded tuberculous serum, like the serum of the blood, inhibits
      proteolysis caused by leucoprotease, but fails to inhibit digestion caused by an
      enzyme acting in the presence of acid. In testing this property of the exuded
      tuberculous serum lymphatic gland has been used because suitable tuberculous
      tissue has not been available. The serum of the tuberculous pleural exudate
      produced experimentally not only fails to exert the anti-enzymotic power which is
      exhibited by the serum of the blood, but is itself capable of causing active
      digestion of coagulated proteid. Normal blood serum does not digest proteid and
      the serum of a sterile inflammatory exudate obtained by injection of turpentine
      into the pleural cavity has caused very little digestion. The tests which have
      been made indicate that loss of anti-enzymotic power and ability to cause
      proteolysis increase with the age of the exudate. The foregoing facts offer
      suggestions which may serve to explain in part the nature of the tubercle and the
      changes which occur within it. The so-called epithelioid cells of the tubercle
      resemble the large mononuclear phagocytes of inflammatory exudates and both
      contain an enzyme of the same character. It is not improbable that caseation
      which, like autolysis, is accompanied by disappearance of nuclei is in part
      dependent upon the presence in the cells of this active proteolytic enzyme which
      is for a time held in check. Injury to cells by products of the tubercle bacillus
      or partial anaemia, the result of imperfect vascularization of the tuberculous
      tissue, may have a part in rendering these cells susceptible to self-digestion.
      Changes which have been observed in serum of the tuberculous exudate show that
      the anti-enzymotic property of the normal blood may be absent in the exudate of a
      tuberculous lesion. This loss of anti-enzymotic action, perhaps referable to
      changes caused by products of the tubercle bacillus, may favor self-digestion of
      the enzyme-containing cells and diffusion of their enzyme.

PMID- 19867157
TI  - THE ENZYMES OF FIBRINOUS EXUDATES-THE EFFECT OF ONE ENZYME UPON ANOTHER.
AB  - By a study of the enzymes contained in fibrinous exudates produced by injection
      of a sterile inflammatory irritant (turpentine) conditions have been found in
      which each of two enzymes occurs alone. The one, leucoprotease, digests in the
      presence of alkali; the other, resembling lymphoprotease, digests in the presence
      of acid, yet both exhibit almost maximum activity in an approximately neutral
      medium. It is probable that both enzymes, in the body, exert their greatest
      activity in an approximately neutral medium, slight changes in reaction
      increasing digestion by the one, and suspending digestion by the other. The
      enzyme digesting in acid, present in the fibrinous exudate obtained after a
      single injection of turpentine, disappears when repeated injection of the same
      irritant transforms the sero-fibrinous into a purulent exudate, and causes
      accumulation of leucoprotease in great quantity.

PMID- 19867158
TI  - ON COMPLEMENT-FIXATION IN MALIGNANT DISEASE.

PMID- 19867159
TI  - AN ANALYSIS OF FOUR HUNDRED CASES OF EPIDEMIC MENINGITIS TREATED WITH THE ANTI
      MENINGITIS SERUM.
AB  - It is our belief that the analyses of histories of cases of epidemic meningitis
      which have been presented in this article furnish convincing proof that the
      antimeningitis serum when used by the subdural method of injection, in suitable
      doses and at proper intervals, is capable of reducing the period of illness; of
      preventing, in large measure, the chronic lesions and types of the infection; of
      bringing about complete restoration to health, in all but a very small number of
      the recovered, thus lessening the serious, deforming, and permanent consequences
      of meningitis; and of greatly diminishing the fatalities due to the disease.

PMID- 19867160
TI  - THE RELATION OF LESIONS OF THE ADRENAL GLAND TO CHRONIC NEPHRITIS AND TO
      ARTERIOSCLEROSIS; AN ANATOMICAL STUDY.
AB  - Vaquez and Aubertin advance three theories in explanation of the adrenal
      hyperplasia; first, that it may not be the cause of hypertension but "an
      antitoxic hyperplasia" caused by the retained products of metabolism which may be
      responsible also for the hypertension; second, that it may be the cause of
      hypertension but secondary to the renal lesion; third, that it may be the cause
      of hypertension but may antedate the renal lesion or be entirely independent of
      it. They, as well as other French writers, insist that this hyperplasia is almost
      constantly associated with chronic nephritis of the interstitial type and it is
      seldom found with the parenchymatous type of nephritis, or with other lesions.
      Hyperplasia of the adrenal, as far as my material enables one to judge, does not
      occur during the first and second decades. In the third decade it is relatively
      frequent in the absence of chronic arterial and renal disease but reaches the
      maximum in association with such disease after the fourth decade. It is an almost
      constant lesion in arteriosclerosis associated with chronic interstitial
      nephritis and left-sided heart hypertrophy, but occurs with almost equal
      frequency in arteriosclerosis with chronic nephritis of the parenchymatous type.
      It is a relatively frequent lesion of arteriosclerosis without chronic nephritis
      and of the latter without arteriosclerosis also. As the result of this analysis
      one is led to the view that while hyperplasia of the adrenal is a very frequent
      concomitant of chronic renal and arterial disease it is not exclusively a feature
      of either type of nephritis or yet of chronic vascular disease; but it probably
      represents the effect of some factor operating in that period of life in which
      chronic renal and arterial affections are most frequent. Worthy of special
      emphasis is the observation that the characteristic lesion of an adrenal, the
      seat of local arteriosclerosis, is of the type of the chronic productive
      inflammation seen in arteriosclerosis of the pancreas and kidney; that is,
      thickening of the vessels, increase of connective tissue and round cell
      infiltration. Associated with these changes is a hyperplasia which is very
      constant, and which may be, in part, of the nature of a compensatory hyperplasia
      similar to that seen in the liver of cirrhosis and acute yellow atrophy. A
      hyperplasia of this type, as has been shown, may occur in destructive lesions of
      the gland. This, however, does not explain hyperplasia in the absence of local
      vascular changes which fact is, possibly, as suggested by Landau, evidence, not
      of a correlation between kidney and adrenal, but of a vicarious hypertrophy
      depending upon lesions of some other organ of the body than the kidney, possibly
      some other ductless gland, affected by arteriosclerosis or other disease.

PMID- 19867161
TI  - A STUDY OF EXPERIMENTAL REDUCTION OF KIDNEY TISSUE WITH SPECIAL REFERENCE TO THE
      CHANGES IN THAT REMAINING.
AB  - The immediate effect of the operation on the portion of the kidney remaining is
      an infarcation of the tissue compressed by the sutures. This area of necrosis
      extends but a short distance into the adjacent kidney tissue. The infarcated
      tissue gradually becomes replaced by fibrous tissue and in three to four week's
      time the necrotic tissue entirely disappears. The amount of fibrous tissue in
      time becomes so slight and the healing so perfect that it is difficult to detect
      the site of the operation. The renal elements sometimes persist in the infarcated
      area and the glomeruli apparently are more resistant than the tubules. The
      tubules in the infarcated area sometimes become calcified and bone formation
      beneath the epithelium of the pelvis is of very frequent occurrence. The pelvic
      epithelium usually shows marked proliferation and may invade the field of
      operation in alveolar masses. Calculi may form in the pelvis of the kidney.
      Sutures penetrating the pelvis as well as the necrotic tissue resulting from the
      compression of the sutures probably furnish the nuclei for the calculi. Removal
      of approximately half of one kidney did not alter either the remaining portion of
      that kidney or the size of the opposite kidney in two animals of this series.
      These experiments were terminated on the thirty-fourth and forty-seventh days. In
      a similar experiment of twenty-one day's duration there was slight but definite
      atrophy of the remaining tissue of the kidney operated upon. Removal of
      approximately half of each kidney at one operation did not alter the remaining
      kidney tissue in two animals of the second group. The longest period of
      observtaion was fifty-four days. On the other hand in a similar experiment where
      164 days elapsed, the remaining portions of each kidney had increased markedly in
      size. Removal of one kidney and approximately half of the other did not alter the
      remaining kidney tissue in six animals in which from five to fifty-six days
      elapsed before termination of the experiment. In six experiments in which one
      kidney was removed and approximately half of the other, three of the animals died
      as a result of the operation on the sixth, seventh and tenth days. The probable
      cause of death was renal insufficiency: the animals refused food, vomited
      persistently and lost strength and weight. The other three animals recovered and
      were killed at periods varying from five to eight weeks. The reduction of the
      kidney tissue to one quarter of its original amount at one operation was attained
      with danger but was not necessarily fatal. In every experiment there was a loss
      of weight varying from four to twenty-four per cent. To what extent this loss in
      weight is due to the reduction of kidney substance and to what extent it is due
      to diet and confinement it is impossible to say, as we made no control
      experiments to elucidate these points.

PMID- 19867162
TI  - ON THE OCCURRENCE OF CATALASE IN HUMAN TISSUES AND ITS VARIATIONS IN DISEASES.
AB  - 1. In work along this line it is most important to have a simple method of
      determining the catalytic activity of tissues. The method must be such that
      several observations can be made during a single experiment, so that a better
      idea can be obtained of the velocity of the reaction at various intervals. 2. The
      catalytic activity of human tissues varies greatly in diseases. A. Nephritis.-The
      kidney always shows the most marked reduction although the other tissues
      examined, blood, lung, liver, spleen, likewise show decrease in their power of
      decomposing hydrogen peroxide. This reduction varies directly with the severity
      of the pathological lesion in the kidney and the clinical symptoms. The urine
      also in cases of nephritis shows a much greater inhibiting power than normal
      urine. This may be accounted for by the reaction of the urine, and subsequent
      work must prove whether or not the kidney takes any more active part in nephritis
      and secretes into the blood and urine a substance which manifests itself by a
      reduction in the catalytic activity. B. The catalytic activity of the blood in
      the two cases of eclampsia which we have studied was not reduced. This is the
      most important fact we have so far obtained, if it can be substantiated, since it
      can furnish us with a ready ante-mortem means of differentiating eclampsia and
      nephritis. C.Pneumonia.-The lung in the stage of red hepatization has an
      increased catalytic activity. This increase varies directly with the number of
      intact red blood cells in the exudate, and in the engorged capillaries. Strength
      is given to this conclusion by the fact, that on the one hand, there is no
      increased activity in gray hepatization, while on the other hand, there is an
      enormously increased activity in the fresh hemorrhagic infarct. D. Tuberculosis.
      The decreased activity of the lung in tuberculosis is probably due, for the most
      part, to the lack of blood in the diseased area, while the lowered activity which
      is present in the other organs is to be explained by the anaemia and emaciation
      which accompanies the process. Whether there is a specific catalytic inhibiting
      substance generated by the process, has not been determined. E. There was no
      reduction of the catalytic activity in the cases of diabetes mellitus and
      jaundice studied. F. In the one case of asphyxiation by illuminating gas, there
      was decided decrease in the catalytic activity of the blood. G. The tissues in
      the one case of congenital syphilis showed a marked lowering of the catalytic
      activity. 3. There is a slight decrease in the catalytic activity of the tissues
      due to post-mortem change, but this is so slight that it is hardly to be taken
      into consideration in the interpretation of the results obtained. 4. There is no
      marked change in the catalytic activity due to age. In concluding, we wish to
      thank Dr. A. S. Loevenhart, at whose suggestion this enzyme was studied, for the
      unfailing interest with which he has followed the progress of this work, and for
      the many valuable suggestions he has given us.

PMID- 19867163
TI  - ON THE EFFECT OF COMPLETE ANEMIA OF THE CENTRAL NERVOUS SYSTEM IN DOGS
      RESUSCITATED AFTER RELATIVE DEATH.
AB  - To determine the limits of recovery after a total anemia of the central nervous
      system, a series of thirty dogs was killed by chloroform and resuscitated after
      varying times from three to fourteen minutes. Under five minutes the recovery of
      function was rapid and strikingly free from the after effects which characterized
      longer periods. Of seven animals between the periods of five and six and one-half
      minutes, only one died apparently as a direct result of the anemia, but of twelve
      between the periods of seven minutes and eight and one-half minutes, only one,
      after seven and one-half minutes recovered. The remaining dogs all died. Further
      corroborative data are drawn from the previously published paper on the technique
      of resuscitation. Histological examination both of presumptive recoveries and
      fatal cases was made by ordinary methods and those of Nissl and Marchi. The
      neurocytes of the fatal cases uniformly presented the greatest change, not merely
      chromolytic but here and there definitely indicative of cell death. Marchi's
      method further supported these findings by proving the existence of fiber
      degeneration. Finally, showing the narrowness of the escape, the animal with best
      result in recovery, seven and one-half minutes in time, which at the end of four
      weeks had apparently entirely returned to a normal state, by the Marchi method
      had a degeneration of a number of fibers localized in the pyramidal fasciculi
      which were traced from the cord to the cortex, and in Flechsig's fasciculus, as
      well as a more sparsely scattered degeneration of both ascending and descending
      fibers elsewhere.

PMID- 19867164
TI  - THE REACTIVE CELL PROLIFERATION IN THE WHITE RAT; AND ITS RELATION TO THE GENESIS
      OF TRANSPLANTABLE TUMORS.

PMID- 19867165
TI  - SOME FACTORS IN THE PHYSIOLOGY AND PATHOLOGY OF GASTRIC SECRETION.

PMID- 19867166
TI  - THE DEPOSITION OF EXOGENOUS COPPER UNDER EXPERIMENTAL CONDITIONS WITH
      OBSERVATIONS ON ITS NEUROTOXIC AND NEPHROTOXIC PROPERTIES IN RELATION TO WILSON'S
      DISEASE.
AB  - Goldfish kept in water containing ionized copper and a detergent added with the
      aim of decreasing coagulation of the mucus on the gills, took in and retained
      this metal in their brains, livers, and kidneys, in concentrations comparable to
      those that occur naturally in Wilson's disease, as chemical assays disclosed.
      Histochemical studies made it clear that much copper had accumulated within the
      large neurons, principally in those of the telencephalon and anterior horn region
      of the spinal cord and in the tubular epithelial cells of the kidneys, the nuclei
      of the parenchymal cells of the liver, the sarcoplasm of the skeletal muscle, and
      in the epithelial covering of the gills. The intraneuronal deposition of copper
      was regularly associated after a time with conspicuous cytologic changes, notably
      contraction and hyperchromaticity of the nerve cells with tortuosity and
      fragmentation of the axis cylinders and lysis and loss of neurons. The
      accumulation of metal in the renal epithelium was frequently accompanied by
      necrosis and was regularly associated with hyperplasia and calcification of the
      epithelial cells of the larger renal tubules in all goldfish kept for prolonged
      periods in copper-rich water. The deposition of copper in the liver was not
      accompanied by consistent cytologic changes. The similarity of the cytologic
      alterations induced in the central nervous systems by copper and those that occur
      naturally in hepatolenticular degeneration in human beings provides evidence that
      copper itself plays an important role in the pathologic alterations of the brain
      in Wilson's disease.

PMID- 19867167
TI  - CELLULAR ORIGIN OF RHEUMATOID FACTOR.
AB  - Fluorescein-labelled aggregated human gamma-globulin was found to react in
      precipitin-type tests with serums of individuals with rheumatoid arthritis. This
      reagent was also highly reactive and specific for the localization of rheumatoid
      factor in frozen sections of synovial membranes, lymph nodes, and subcutaneous
      nodules. In synovial membranes from patients with active rheumatoid arthritis,
      rheumatoid factor was present in the cytoplasm of plasma cells at various stages
      of development and maturity. The appearance of the cytoplasm and the occasional
      presence nearby of extracellular particles suggested the possibility of a
      secretory process. All other cells were devoid of rheumatoid factor. Some plasma
      cells contained 7S and/or 19S gamma-globulin and many lacked detectable gamma
      globulin. In lymph nodes from a patient with active rheumatoid arthritis,
      rheumatoid factor was present in approximately one in ten germinal centers as
      well as in internodular plasma cells. The rheumatoid factor was localized in the
      cytoplasm and the characteristic protoplasmic processes of the germinal-center
      cells. All other cells were devoid of rheumatoid factor. 7S and/or 19S gamma
      globulin was demonstrated in approximately eight in ten germinal centers in these
      lymph nodes. Plasma cells with rheumatoid factor were also seen on occasion in
      rheumatoid subcutaneous nodules. Tissue sections of comparable structure prepared
      from normal and pathological control material did not contain rheumatoid factor.
      Staining for rheumatoid factor was blocked by pretreatment of sections either
      with unlabelled aggregated human gamma-globulin or with rabbit antiserum against
      19S human gamma-globulin.

PMID- 19867168
TI  - A VIRUS-INDUCED EPIZOOTIC HEMORRHAGIC DISEASE OF THE VIRGINIA WHITE-TAILED DEER
      (ODOCOILEUS VIRGINIANUS).
AB  - A circumscribed natural outbreak of a highly fatal disease of deer, which we have
      designated epizootic hemorrhagic disease (EHD), has been studied. The disease has
      proven readily transmissible in deer but not in other experimental or domestic
      animals tested, nor in embryonating eggs or deer kidney cell cultures. The
      causative agent is a virus which is readily filterable and is capable of storage,
      either frozen or in glycerol, for relatively long periods of time. It produces a
      solid immunity in the few animals that survive and the blood sera of such
      convalescent animals contain virus-neutralizing antibodies. The disease is one in
      which large and small hemorrhages occur in both the viscera and skeletal
      structures of the body, as well as in the subcutaneous tissues. It is probably
      the same as one known popularly in the southeastern United States as "black
      tongue" of deer. It is unrelated to epidemic hemorrhagic fever of man or to the
      disease caused in horses by the equine arteritis virus. At least two
      serologically different types of EHD virus exist. The New Jersey strain is of
      greater lethality for experimental deer than the serologically different one
      obtained from an outbreak that occurred in South Dakota a year after the New
      Jersey epizootic.

PMID- 19867169
TI  - THE PATHOLOGIC EFFECTS OF INTRAVENOUSLY ADMINISTERED SOLUBLE ANTIGEN-ANTIBODY
      COMPLEXES : II. ACUTE GLOMERULONEPHRITIS IN RATS.
AB  - The intravenous administration to rats of soluble antigen-antibody complexes in
      antigen excess resulted in acute glomerulonephritis. This occurred with both
      rabbit antiovalbumin and rabbit anti-BSA systems. The rats so treated regularly
      showed proteinuria and elevation of blood urea nitrogen. These findings are
      compared with those reported in rats injected with anti-kidney serum.

PMID- 19867170
TI  - RELATION OF A beta(1)-GLYCOPROTEIN OF HUMAN SERUM TO THE COMPLEMENT SYSTEM.
AB  - The protein of human serum, tentatively designated beta(1C)-globulin, was shown
      to possess serological activity and to be related to the complement system.
      Another serum protein (beta(1A)-globulin) was identified as the inactivated form
      of beta(1C)-globulin. Incubation of fresh serum with various immune precipitates
      or with soluble gamma-globulin aggregates at 37 degrees C. resulted in the
      removal of beta(1C)-globulin. Treatment of fresh serum with zymosan at 17 and 37
      degrees C. had a similar effect. In both instances beta(1C)-globulin was removed
      from serum, apparently by conversion to beta(1A)-globulin. However, isolated
      beta(1C)-globulin did not react with immune precipitates or zymosan, nor did
      beta(1C)-globulin of serum previously heated at 56 degrees C. Highly purified
      beta(1C)-globulin was tested for complement component activity by means of the
      usual reagents. All of the preparations examined were found to reconstitute the
      hemolytic activity of guinea pig R(3). However, they failed to reconstitute R(3)
      obtained from human serum. Isolated beta(1A)-globulin was found to be inactive in
      all systems. When isolated beta(1C)-globulin in either phosphate or in borate
      buffer was stored at 37 degrees C., the activity detected by means of guinea pig
      R(3) declined within 6 days to 20 to 30 per cent of its original value. As the
      activity decreased, beta(1C)-globulin was gradually converted to beta(1A)
      globulin. Addition of beta(1C)-globulin to a limited complement system (human C')
      caused an increase of both initial velocity and final degree of hemolysis.
      Although beta(1C)-globulin did not cause lysis of EAC'(1, 4, 2), it fully
      prevented the otherwise rapid decay of EAC'(1, 4, 2) at 37 degrees C., and so
      presumably interacted with this complex.

PMID- 19867171
TI  - STUDIES ON ANTIBODY FORMATION BY PERITONEAL EXUDATE CELLS IN VITRO.
AB  - Cells from peritoneal exudates of rabbits sacrificed 3 days after an
      intraperitoneal injection of sterile mineral oil were grown in tissue cultures in
      medium 199 (75 per cent); normal rabbit serum (25 per cent). Antibody produced by
      the cells was assayed by an hemagglutination technique in which the antigens used
      were adsorbed to formalinized tanned sheep erythrocytes. These sensitized cells
      agglutinate in the presence of antibody specific to the adsorbed antigen. It has
      been demonstrated that: Peritoneal exudate cells produced hemagglutinating
      antibody to bovine gamma globulin (BGG) in a replicating tissue culture system
      for approximately 3 weeks when taken from animals given either primary or
      secondary injections of BGG. The mean hemagglutinating titer was 30 for the
      primary and 32 for the secondary systems. Since the other cell types did not
      persist, it is felt that monocytes were responsible for these results. Monocytes
      taken from normal rabbits and exposed to either BGG or egg albumen (EA) in vitro
      produced titers of 28 for about 2 weeks. Monocytes taken from rabbits given
      hyperimmunizing injections of BGG produced titers of 147 for about 1 week.
      Endotoxin from Salmonella typhosa caused the monocytes to form antibody as if
      they had been taken from hyperimmunized rabbits. This was true both when the
      antigen was given in vivo together with the endotoxin as well as when the cells
      were exposed to antigen in vitro. The titers were 223 and 97, respectively.
      Neither freshly harvested nor cultured monocytes were phagocytic for carbon
      particles or bacteria in vitro. Monocytes in tissue culture appeared to assume
      the morphology of fibroblasts, but did not stain with the characteristics of
      fibroblasts. The morphologic changes and staining characteristics of monocytes in
      tissue culture have been described. The implications of these findings have been
      discussed and an attempt made to integrate them into general biological theory.

PMID- 19867172
TI  - EXPERIMENTAL IMMUNOLOGIC ADRENAL INJURY : A RESPONSE TO INJECTIONS OF AUTOLOGOUS
      AND HOMOLOGOUS ADRENAL ANTIGENS IN ADJUVANT.
AB  - Twenty-three unilaterally adrenalectomized guinea pigs were injected with
      autologous and homologous adrenal tissue homogenates respectively, in Freund's
      adjuvant. Widespread adrenal lesions were found in 10 of 12 animals receiving
      auto-antigen and to a lesser extent in 6 of 11 animals injected with homologous
      pooled antigen. Widespread systemic lesions were present in both these and in
      control animals receiving Freund's adjuvant alone. These latter animals showed no
      adrenal involvement. The early changes within the adrenal consisted of
      perisinusoidal cellular proliferations in the deeper layers of the cortex. Focal
      granulomata developing at a later stage tended to become confluent and to
      displace cortical cells. Some loss of these cells was attributable to ischemic
      injury. The localization in the deep fasciculata and reticularis was thought to
      depend (a) on the varying antigenicity of adrenal cortical components, (b) the
      possible inhibitory effect of antiphlogistic adrenal cortical hormones on the
      development of lesions in the outer cortex, and (c) the presence of littoral
      cells in the deep cortex. These cells are thought to be involved in the mediation
      of the stimulus initiating differentiation of primitive mesenchymal cells in
      response to a circulating auto-antigen. The medullary lesions may be related to
      the presence of ectopic reticularis cells in this location. It was suggested that
      the cellular response in the target organ to injections of adrenal homogenates
      may denote a specific "organ-self" recognition mechanism involving an immune
      (i.e. defensive) reaction. It was postulated that this may be an accentuation of
      the physiological function of immunologically competent cells. Their
      proliferation, under normal circumstances, would prevent by means of production
      of "binding" globulins, the escape and dissemination of endogenous freed adrenal
      antigens into the circulation. Although the experimental stimulus arose from
      without the gland, by virtue of the presence of a circulating adjuvant-bound
      antigen, the adrenal reaction followed the same pattern as would obtain if the
      antigen was liberated within the suprarenal cortex.

PMID- 19867173
TI  - DEPRESSION BY ANTIBODY OF THE IMMUNE RESPONSE TO HOMOGRAFTS AND ITS ROLE IN
      IMMUNOLOGICAL ENHANCEMENT.
AB  - This paper reports tests of two hypotheses that have been proposed to account for
      the enhanced growth of tumor homografts in the presence of antiserum reactive
      with the graft (immunological enhancement). According to the first hypothesis,
      enhancement is due to some "physiological" alteration in the tumor, induced by
      its contact with antiserum, which insures its survival despite the hostile
      response of the host. According to the second hypothesis, antiserum alters the
      response of the host. By blocking the development of the cellular type of
      immunity, which is the main agent in graft destruction, it permits the graft to
      survive. To test hypothesis 1, strain A tumor SaI was passed from A's, and from
      enhanced B10.D2's, into untreated B10.D2's. The per cent of deaths was
      essentially the same in both groups (48 and 44 per cent, respectively); there was
      no evidence that passage through enhanced B10.D2's altered the capacity of the
      tumor to grow in the foreign strain. Several other groups of mice included in the
      experiment all confirmed this conclusion. The experiment failed to confirm
      hypothesis 1. In the tests of hypothesis 2, the effect of isoantiserum on immune
      responses of both the humoral and cellular type was measured. When antiserum was
      given together with foreign strain lymphoid cells (antigen), almost no additional
      antibody was manufactured; in contrast with this, controls receiving foreign
      cells only produced red cell agglutinating antibody in high titer. The effect of
      antiserum on the development of immunity of the cellular type was tested by the
      method of Winn. In this assay, presumptively immune node cells, in various
      dilutions, are mixed with tumor cells and injected into appropriate mice.
      Immunity is indicated by inhibited tumor growth. Antiserum given at the same time
      as a tumor homograft greatly depressed the immunity of the cells expressed from
      the draining nodes. At 6 days after the graft, the level of immunity of cells
      from treated mice was 1/24th to 1/32nd that of cells from controls receiving
      tumor alone. The same sort of depressing effect was noted when the immunizing
      tissue was foreign thymus or embryo. Antiserum given 1 or more days after the
      immunizing tissue also resulted in a lower level of cellular immunity (but the
      assay used in this case was a less critical one). These results provide an
      adequate explanation of the phenomenon of immunological enhancement, at least as
      it occurs in the particular test system used in these experiments. Since it is
      cellular immunity rather than humoral antibody that inhibits the growth of most
      grafts (transplantable leukemias are an exception), the depression of this
      immunity by antibody is favorable to the growth of a homograft.

PMID- 19867174
TI  - THE EFFECT OF DIPHTHERIA TOXIN ON THE METABOLISM OF HELA CELLS : II. EFFECT ON
      NUCLEIC ACID METABOLISM.
AB  - The effect of toxin on the incorporation of uridine and thymidine into nucleic
      acids was investigated. P(32) orthophosphate incorporation into the nucleoside
      phosphate fraction was also investigated. No early effect of toxin on nucleic
      acid synthesis was evident and only a slight effect of toxin on nucleoside
      phosphate formation was found prior to 1.5 hours after toxin addition. Both these
      processes, however, were found to be sensitive to dinitrophenol. These results
      are interpreted as indicating that toxin does not act by a general uncoupling of
      oxidation from phosphorylation. Other possible mechanisms of toxin action are
      proposed.

PMID- 19867175
TI  - THE EXPERIMENTAL DISEASE THAT FOLLOWS THE INJECTION OF HUMAN LEPROSY BACILLI INTO
      FOOT-PADS OF MICE.
AB  - When leprosy bacilli from human patients are inoculated into the foot-pads of CFW
      mice, a microscopic granuloma containing acid-fast bacilli develops in a
      characteristic manner. This has been seen in 22 of 22 instances with leprosy
      bacilli from nasal washings, in 12 of 16 instances with leprosy bacilli from skin
      biopsies, and in none of 16 cases where the nasal washings were not observed to
      contain leprosy bacilli. Quantitative studies revealed a relationship between the
      number of bacilli inoculated and the time required for the appearance of the
      lesions. The incubation period was usually 1 to 2 months when the dose was
      10(5.5) to 10(6.0) bacilli and about 6 months when the dose was about 10(3)
      organisms. After the development of the lesion, the number of bacilli harvested
      was usually in the range 10(4.5) to 10(6.0), regardless of the number inoculated.
      When the inoculum has contained 10(2.0) to 10(3.5) acid-fast bacilli, and
      harvests were reasonably prompt, there were regular increases of 50- to 1000
      fold. Passage to new groups of mice has been successful 11 of 12 times. Most of
      these were second passages. One strain has been maintained in 3 passages with a
      total increase in acid-fast bacilli of 4 x 10(4)-fold. Another strain has been
      through 4 passages with a total increase of about 4 x 10(6)-fold. Cultures on
      bacteriological media favorable for the growth of most known mycobacterial
      species have not shown growth of mycobacteria.

PMID- 19867176
TI  - THE MOVEMENT OF ELECTROLYTES AND OF WATER IN SURVIVING TISSUE OF THE LIVER.
AB  - When liver slices immediately after their removal from the body are immersed in
      graded solutions of sodium chloride, movement of water does not follow a course
      determined by movement of sodium ions. From hypotonic solutions sodium enters
      slowly and swelling proceeds rapidly but with increasing concentration entrance
      of sodium increases and swelling diminishes in accord with the osmotic relations
      between tissue and the medium. The extracellular fluid of liver has the same
      osmotic pressure as blood plasma, and entrance of water into liver slices from
      media with greater molar concentration is determined by the intracellular
      pressure of the parenchymatous cells of the tissue. The plasma membrane of the
      liver cell is semipermeable to electrolytes but its semipermeability is
      imperfect, may be impaired, and when in media isotonic with the cells some of the
      electrolyte enters them. With continued entrance permeability to both electrolyte
      and water increases and in case of sodium become evident after 15 or 20 minutes.
      A medium more favorable to the tissue prolongs the period of isotonicity. In
      solutions with electrolytes otherwise similar to those of the blood plasma, e.g.
      Krebs-Ringer solution, but with molar concentration of electrolytes approximately
      doubled by addition of sodium chloride isotonicity may be prolonged during a
      period of 1 hour or more. When potassium chloride is added to the Krebs-Ringer
      solution so that its potassium content has been increased 10-fold the water
      intake of liver cells has not varied in accord with the potassium content of the
      medium. In a medium with the electrolyte contents of blood plasma (Krebs-Ringer
      solution) liver cells after 1 hour gain sodium and lose potassium, but later
      potassium maintains a nearly constant level though swelling increases. Less
      sodium enters and less potassium is lost from liver cells at 0 degrees C. than at
      38 degrees and 0 degrees C. swelling is greater. Movement of water between cells
      and extracellular fluid may occur independently of changes in the sodium or of
      potassium content of cells and doubtless is in part determined by substances
      associated with metabolism.

PMID- 19867177
TI  - THE MAMMALIAN CELL-VIRUS RELATIONSHIP : V. SUSCEPTIBILITY AND RESISTANCE OF CELLS
      IN VITRO TO INFECTION BY COXSACKIE A9 VIRUS.
AB  - All primary cell cultures tested from numerous human and rhesus monkey tissues
      were susceptible to Coxsackie A9 virus infection and were found to contain a
      specific A9 virus receptor. Ability of these cells to adsorb actively virus
      correlated with the presence of this receptor. Attachment of A9 virus to cell
      receptor was specifically enhanced by calcium and magnesium ions. Human cells
      established in continuous culture from pretested susceptible cultures were found
      to have lost A9 virus susceptibility and A9 receptors but not receptors for
      adsorption of type 1 poliovirus or B1, B3, B5 Coxsackie viruses. These cultures
      were able also to produce infectious A9 virus after exposure to viral RNA.
      Coxsackie A9 virus as well as type 1 poliovirus, inactivated following reaction
      with debris prepared from susceptible cells, could be recovered fully in
      infectious form by treatment of the inactive systems at low pH. Recovery of
      infectious A9 virus was also possible with a chelating compound. Coxsackie A9
      virus could also be dissociated by means of low pH after adsorption onto
      susceptible cells for 2 minutes at 1 degrees C., but not after 1 hour incubation
      at 37 degrees C., indicating that viral host cell activity may be required in
      order for irreversible enterovirus attachment to take place.

PMID- 19867178
TI  - STUDIES ON THE PATHOGENESIS OF RABIES IN INSECTIVOROUS BATS : II. INFLUENCE OF
      ENVIRONMENTAL TEMPERATURE.
AB  - Studies on the influence of environmental temperature on the pathogenesis of
      rabies in two species of experimentally infected Chiroptera, the Mexican free
      tailed bat (Tadarida mexicana) and the little brown bat (Myotis lucifugus),
      provided evidence that little or no viral multiplication occurs in the inactive
      host during experimentally induced hibernation. When inoculated animals are
      wakened from hibernation by transfer to a warm room, virus previously in "cold
      storage" multiplies, reaching detectable levels in various tissues. Similar
      results were obtained with two strains of rabies virus, a canine rabies street
      virus which produced a fatal infection in man and a strain isolated from the
      pooled brown fat of naturally infected little brown bats. However, certain
      differences in the characteristics of these virus strains were observed. The
      canine rabies virus strain produced an encephalitic disease in mice and overt
      symptoms in bats; the bat rabies virus producing an encephalomyelitic disease in
      mice and infrequent symptoms in bats. The bat rabies virus had a greater
      predilection for brown adipose tissue than the canine strain. Results obtained
      with the bat rabies virus in hibernating animals indicate that after a period of
      latency in a dormant animal activated virus may reach the salivary gland more
      rapidly, with greater frequency, and attain higher concentrations than in animals
      which have not experienced a period of hibernation. The significance of these
      results as they relate to the natural history of bat rabies is discussed.

PMID- 19867179
TI  - STUDIES ON THE EFFECT OF CERTAIN MACROMOLECULAR SUBSTANCES ON THE RESPIRATORY
      ACTIVITY OF THE LEUCOCYTES OF PERIPHERAL BLOOD.
AB  - The oxygen, uptake of lightly heparinized human blood was found to increase
      markedly upon the addition of bacterial endotoxins, soluble antigen-antibody
      complexes, or polystyrene latex particles. The effect apparently reflects a
      transitory stimulation of respiratory activity of the blood leucocytes. The
      effect did not occur in the presence of anticoagulant amounts of citrate or
      ethylenediaminetetraacetate, was inhibited by iodoacetate and fluoride ions, and
      may be related to the energy-yielding processes involved in histamine release or
      phagocytosis.

PMID- 19867180
TI  - METABOLISM OF ACID MUCOPOLYSACCHARIDES IN THE SHWARTZMAN PHENOMENON.
AB  - The effect of the Shwartzman phenomenon on the metabolism of the acid
      mucopolysaccharides (MPS), hyaluronic acid and chondroitin sulfate, from rabbits
      with localized lesions was studied. Quantitative changes of MPS were observed by
      two techniques-the in vivo incorporation of glucose C(14) into the MPS and the in
      vitro dilution of C(14)-labeled MPS. The results indicate an increased
      concentration of both MPS fractions in the skin lesions and suggest an increased
      biosynthesis of the compounds at the site of the lesions. Deposition of
      chondroitin sulfate from blood may have contributed in part to the concentration
      of this substance in the lesions. The MPS contribute to the inflammatory state of
      the Shwartzman phenomenon but the specific roles of these compounds need to be
      defined by further study.

PMID- 19867181
TI  - CORRELATION OF PRODUCTION OF INFECTIOUS VIRUS WITH SEQUENTIAL STAGES OF CYTOLOGIC
      ALTERATION IN HELA CELLS INFECTED WITH ADENOVIRUSES TYPES 5 AND 7.
AB  - Studies correlating the production of infectious adenovirus (types 5 and 7) and
      the progression of the stages of virus-induced cytologic change in HeLa cells are
      presented. The results reveal a close relationship between the development of the
      characteristic nuclear changes and adenovirus synthesis. They suggest that cells
      manifesting the first stages of nuclear change, characterized by the appearance
      of eosinophilic, Feulgen-negative inclusions, contain little or no mature
      infectious virus, whereas cells in the later stages, with Feulgen-positive and
      basophilic inclusions, contain relatively large amounts.

PMID- 19867182
TI  - STUDIES OF TWO KINDS OF VIRUS PARTICLES WHICH COMPRISE INFLUENZA A2 VIRUS STRAINS
      : I. CHARACTERIZATION OF STABLE HOMOGENEOUS SUBSTRAINS IN REACTIONS WITH SPECIFIC
      ANTIBODY, MUCOPROTEIN INHIBITORS, AND ERYTHROCYTES.
AB  - Two kinds of virus particles have been found in varying proportions in influenza
      A2 strains isolated during the 1957 pandemic. Pure populations of the different
      particles were obtained, and these substrains were genetically stable on serial
      passage in the chick embryo. The two virus particles differ markedly in several
      biological properties though they are antigenically similar. One kind of
      particle, designated "+," is relatively sensitive to specific antibody, is highly
      sensitive to inhibition by serum inhibitors and urinary mucoprotein, fails to
      elute or elutes very slowly from human erythrocytes, and is capable of
      agglutinating erythrocytes treated extensively with V. cholerae filtrate. The
      other particle, designated "-," is relatively insensitive to antibodies and
      urinary mucoprotein, completely insensitive to serum inhibitors, elutes rapidly
      from erythrocytes, and can agglutinate erythrocytes treated extensively with V.
      cholerae filtrate. Both "+" and "-" particles destroy virus receptors on urinary
      mucoprotein. The relative proportions of these two particles determine the
      characteristics of parent strains in reactions with specific antibody,
      mucoprotein inhibitors, and erythrocytes. The "+" and "-" particles with several
      easily identifiable markers are well suited for genetic studies.

PMID- 19867183
TI  - TISSUE MAST CELLS AND ACUTE INFLAMMATION IN EXPERIMENTAL CUTANEOUS MUCORMYCOSIS
      OF NORMAL, 48/80-TREATED, AND DIABETIC RATS.
AB  - The role of the tissue mast cells in relation to the acute inflammatory reaction
      to experimental cutaneous mucormycosis was studied histologically in normal rats,
      in animals whose tissue mast cells had been depleted of their cytoplasmic
      granules prior to infection by the administration of compound 48/80 and in others
      in whom acute alloxan diabetes with acidosis had been produced before injection
      of the fungus. The discharge of the tissue mast cell granules in normal rats
      occurred within minutes at the site of infection and appeared to initiate the
      rapid onset of acute inflammation. The degranulation of the tissue mast cells
      subsided in a short time and the cells reassumed a normal histologic appearance
      while inflammation progressed with the formation of circumscribed lesions. In
      animals pretreated with compound 48/80 in which the tissue mast cells contained
      no granules, the onset of inflammation was briefly delayed, the intensity of the
      process was somewhat decreased, fibroblastic proliferation was retarded, and the
      fungus growth in the early lesions was increased. However, the infection did not
      spread and the lesions were well localized. The tissue mast cells in the diabetic
      and acidotic rats completely failed to discharge their cytoplasmic granules, the
      onset and intensity of the acute inflammatory response were markedly delayed and
      decreased and the infection progressed rapidly with massive fungus growth
      invading adjacent tissues. A relationship between the discharged tissue mast cell
      granules and eosinophilic granulocytes was noted since the latter were numerous
      among the inflammatory cell exudate in normal rats and scarce in the lesions of
      the diabetic animals. It is concluded that a function of the tissue mast cells in
      the normal rat is the rapid initiation of acute inflammation at the site of
      injury and that degranulation of these cells prior to infection somewhat delays
      the inflammatory response and therefore slightly diminishes host resistance.
      Furthermore, a severe metabolic disorder such as acute alloxan diabetes with
      acidosis, inhibits the normal function of the tissue mast cells, delays and
      decreases inflammation, and in this manner contributes to the greatly increased
      susceptibility of the host to infection.

PMID- 19867184
TI  - STUDIES ON IMMUNE HUMAN HEMOLYSIS : II. THE DONATH-LANDSTEINER REACTION AS A
      MODEL SYSTEM FOR STUDYING THE MECHANISM OF ACTION OF COMPLEMENT AND THE ROLE OF
      C'1 AND C'1 ESTERASE.
AB  - 1. The inactivation, of C'1 blocks the completion of the cold phase of the Donath
      Landsteiner reaction; inactivation of the other components of complement does not
      interfere with the cold phase of the reaction. 2. C'2, C'3, and C'4 are required
      for the completion of the hemolytic reaction. C'4 reacts in either the cold or
      warm phase, but C'2 and C'3 must react in the warm phase. 3. Partially purified
      C'1 or C'1 esterase can be substituted for whole serum in the cold phase,
      although neither reagent contains any of the other components of complement 4.
      Partially purified serum inhibitor of C'1 esterase blocks the effect of C'1
      esterase in the cold phase, and reverses the effect of complement, C'1 or C'1
      esterase when incubated with "activated" cells after the cold phase. 5. C'1
      esterase activity can be eluted from "activated" erythrocytes with Na(3)EDTA. 6.
      The components of human complement in this human hemolytic reaction act in the
      order C'1, C'4, C'2, C'3. Ca(++) is required for the reaction with C'1, and
      Mg(++) is required for the reaction with C'2. 7. Accordingly, a functional role
      of C'1 esterase in a human disease state is demonstrated, and a human model is
      established for the study of the mechanism of action of complement.

PMID- 19867185
TI  - EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM : III. NITROGEN EXCRETION AFTER
      ACTH AS AN ASSAY FOR ENDOTOXIN.
AB  - There exists an inverse proportionality between number of heat-killed cells of
      Salmonella typhimurium injected intraperitoneally into mice and the quantity of
      urinary nitrogen the animals excrete during a 17 hour period following the
      subcutaneous administration of 2 units of ACTH. This relationship has been
      developed into an assay for bacterial endotoxin. Mice immunized against S.
      typhimurium require 10 to 20 times the number of cells needed by control animals
      to suppress urinary nitrogen excretion to the same extent. Intravenous
      saccharated iron oxide sensitizes animals so that fewer heat-killed salmonellae
      can be detected. Heat-killed cells of Staphylococcus aureus are without effect in
      the assay. Several lipopolysaccharides derived from Gram-negative bacteria are
      effective in preventing the rise of urinary nitrogen excreted in response to ACTH
      and the amount required, compared to the LD(50), is in the same ratio for all of
      them. Citrated mouse serum partially inactivates the endotoxin during in vitro
      incubation for 1 hour at 37 degrees C. while normal serum does not.
      Dichloroisoproterenol protects mice against the lethal effects of
      lipopolysaccharide and it lowers its effectiveness in the assay. The minimum
      amount of endotoxin reliably determined by the test is 0.25 microg. of an E. coli
      preparation that was given intravenously in mice in which the reticuloendothelial
      system had been "blocked" with saccharated iron oxide.

PMID- 19867186
TI  - STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION : I. THE EFFECT OF
      REPEATED SKIN INFECTIONS.
AB  - The influence of repeated staphylococcal infection of rabbit skin upon the
      characteristics of the experimentally induced lesion was studied. It was found
      that the repeated infection was associated with the development of delayed
      hypersensitivity unaccompanied by the appearance of demonstrable serum antibody.
      The delayed hypersensitivity to the staphylococcus resulted in an increased
      infectivity of the organism in skin of the sensitized animal, characterized by
      intensification of the lesions seen with large bacterial inocula and the
      induction of abscesses with inocula incapable of producing any lesion in normal
      rabbit skin. Similarly, the severity of experimentally induced pyoarthrosis was
      greater in sensitized than in normal rabbits. Induction of delayed
      hypersensitivity by vaccination of rabbits with washed heat-killed staphylococci
      resulted in the same increased severity of the infection and an increase in
      infectivity of the microorganism. In contrast to the observations of cutaneous
      and joint infection, the sensitized animals appeared to be less susceptible to
      severe infection of the anterior chamber of the eye. The role of immunity and
      hypersensitivity in staphylococcal infection is discussed and the possibility
      that non-specific inflammation may influence staphylococcal infection in the same
      way as specific hypersensitivity is indicated. Studies to further elucidate this
      are presented in the following pages.

PMID- 19867187
TI  - STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION : III. THE EFFECT OF
      TISSUE NECROSIS AND ANTITOXIC IMMUNITY.
AB  - Necrosis of rabbit skin produced by thermal injury was found to result in a
      striking increase in local infectivity of staphylococci that were coagulase
      positive and hemolytic, but no local increase in the infectivity of non
      pathogenic staphylococci. Infection produced in necrotic burns extended beyond
      the area of burn and was characterized by hemorrhage, edema, and necrosis of
      contiguous normal skin. Such infections, however, never resulted in bacteriemia
      or metastatic abscesses, and there was no effect of the necrotic burn upon the
      infectivity of staphylococci injected into normal skin of the burned animal.
      Recovery of rabbits from severe burn infections was associated with the
      development of high titers of serum antibody to the alpha hemolysin or
      dermonecrotoxin of the staphylococcus. Thirty to 100 days after the initial burn
      infection, it was found that rabbits could no longer be infected in a necrotic
      burn, although infection induced in normal skin of these resistant animals was no
      different from that in normal rabbits. Immunity to infection by pathogenic
      staphylococci in necrotic burns could be induced by vaccination with potent alpha
      hemolysin toxoid, and this immunity was passively transferable with rabbit
      antiserum. No strain specificity was detected for this immunity in that
      immunization with toxoid prepared from bacteriophage type 52/42B/80/81
      staphylococci protected animals against infection in a necrotic burn by other
      typable and non-typable staphylococci. Histopathological study of infected
      necrotic burns in normal rabbits showed extensive necrosis, hemorrhage, edema,
      and many masses of bacteria but leucocytic infiltration was observed only at the
      margin of the infection. In contrast, the infected necrotic burns in animals
      immunized with alpha hemolysin toxoid showed few bacteria and marked leucocytic
      infiltration throughout the burn. These experiments have, therefore, demonstrated
      a significant immunity to infection by pathogenic staphylococci in necrotic
      tissue but not in normal skin, associated with serum antibody to the alpha
      hemolysin or dermonecrotoxin of the bacteria. The implications of these findings
      are discussed.

PMID- 19867188
TI  - AN IMMUNIZING SUBSTANCE FOR SEMLIKI FOREST VIRUS IN THE LIVERS OF IMMUNE MICE :
      I. THE INITIAL OBSERVATION TOGETHER WITH A CONSIDERATION OF THE ATTENDING
      CONDITIONS.
AB  - A material capable of rendering mice resistant to Semliki Forest virus is present
      in the livers but not in the muscles, brains, or spleens of mice that have
      survived a usually fatal dose of virus.

PMID- 19867189
TI  - PREPARATION AND EFFECTS OF AN ANTI-MAST CELL SERUM.
AB  - In an attempt to obtain an antiserum that would bring about widespread
      destruction of mast cells in the rat, rabbits were immunized with mast cells
      isolated from the peritoneal cavities of rats. Striking evidence of anti-mast
      cell activity was indicated in vivo by mast cell disruption and in vitro by
      positive interfacial precipitin tests of the serum from rabbits so treated. The
      time course of the production of anti-mast cell activity in the rabbit serum was
      established. Normal rabbit serum was without effect on mast cells in the several
      tests. The same was true for rabbit anti-rat liver serum except when it was
      applied directly to tissues containing mast cells. In the latter case mast cell
      disruption ensued, but it appeared different from that evoked by anti-mast cell
      serum. Intraperitoneal injection of anti-mast cell serum was followed by
      destruction of all of the mast cells of the mesentery and of the majority of mast
      cells in the ear, scrotum, and abdominal skin. The time course of this
      destruction, of the phagocytosis of the mast cell debris, and of the repopulation
      of the tissues with new mast cells was established. Attending the disruption of
      mast cells the levels of tissue histamine dropped sharply but returned toward
      normal as new mast cells appeared. In the scrotum and abdominal skin 5
      hydroxytryptamine did not fall below normal and was markedly above normal at the
      time when histamine and mast cell content were lowest. Reddening and swelling of
      the muzzle, ears, feet, and scrotum were present during the first few days after
      injection of the anti-mast cell serum. Intraperitoneal injection of normal rabbit
      serum was without any of the above effects. Similarly injected rabbit anti-rat
      liver serum had no effect on the mast cells or upon the levels of histamine and 5
      hydroxytryptamine in the ear, scrotum, or abdominal skin. It caused no reddening
      and swelling of the muzzle, ears, feet, and scrotum. It was attended, however, by
      destruction of the mast cells and by a sharp fall in the histamine content of the
      mesentery. Gross changes in the tissue of the peritoneal cavity following anti
      mast cell and anti-liver serum were described. The possible significance of the
      several findings were discussed.

PMID- 19867190
TI  - THE CHANGES IN SERUM PROTEINS AND BLOOD VOLUME DURING IMMUNIZATION.
AB  - In rabbits hyperimmunized with pneumococcal vaccine high concentrations of gamma
      globulin are produced. In such rabbits, plasma volume was determined with (131)I
      labelled rabbit albumin and red cell volume with (51)-Cr-labelled autologous red
      cells. It was found that the plasma volume increased with increasing gamma
      globulin concentration, the highest values observed being about 10 gm. per cent
      gamma globulin and about 70 ml. plasma per kg as against normal values of 0.6 to
      0.7 gm. per cent gamma globulin and 30 ml. plasma per kg. The red cell volume was
      the same in immunized and in normal rabbits and consequently hemoglobin
      concentration fell with increasing gamma globulin.

PMID- 19867191
TI  - BLOOD GROUP ACTIVITY OF GRAM-NEGATIVE BACTERIA.
AB  - Distribution of blood group A, B, and H(O) activities among 282 aerobic Gram
      negative bacteria, many isolated from the blood of patients, has been studied.
      Almost half of these bacteria were found to be blood group active. About 10 per
      cent of the organisms exhibited high, disproportional activities, which in some
      instances approached those of crude human blood group mucoids. No significant,
      specific D (Rh(o)), M, or N activity was found in approximately 70 members of the
      Enterobacteriaceae. An attempt was made to correlate the observed activity of a
      given organism of known O somatic antigen with its monosaccharide components. The
      presence of those sugars which account for the specificity of human blood group
      mucoids was noted. The bearing of these findings on the origin of human anti-A
      and anti-B isoantibodies has been mentioned.

PMID- 19867192
TI  - DEMONSTRATION OF MOUSE ISOANTIGENS AT THE CELLULAR LEVEL BY THE FLUORESCENT
      ANTIBODY TECHNIQUE.
AB  - The fluorescent antibody technique has been applied for the demonstration of
      mouse isoantigens at the cellular level. Specific reactions were obtained by the
      indirect or "sandwich" technique with a variety of living normal and neoplastic
      cells. Isoantigens of the H-2 system and of other systems could be demonstrated
      as well and appeared to be localized at the cell membrane. As far as the H-2
      system was concerned, the membrane localization could be confirmed on
      histological sections. Different types of non-specific staining reactions have
      been identified and described. Pinocytosis and cell injury led to such reactions
      that were morphologically distinguishable from the specific "ring" reaction and
      as far as pinocytosis is concerned, could be easily avoided by reducing the
      incubation time. In addition, a non-specific staining reaction morphologically
      indistinguishable from the specific "ring" reaction could be seen in a small
      proportion of bone marrow and lymph node cells but in no other cell type studied.
      The possible nature of this reaction is discussed.

PMID- 19867193
TI  - COMPARATIVE STUDIES IN ROUS SARCOMA WITH VIRUS, TUMOR CELLS, AND CHICK EMBRYO
      CELLS TRANSFORMED IN VITRO BY VIRUS : I. PRODUCTION OF MUCOPOLYSACCHARIDES.
AB  - The chick embryo fibroblast infected by Rous sarcoma virus in vitro acquires the
      capacity to produce the acid mucopolysaccharides which are found in the tumors
      caused by this virus and which are also produced by tumor cells in vitro. The
      transformed cell acquires synthetic as well as morphologic, metabolic, and
      proliferative properties characteristic of Rous sarcoma tumor cells in vivo and
      in vitro and the transformed cell may be analogous to the tumor cell produced by
      virus infection in vivo.

PMID- 19867194
TI  - INDICATIONS OF HEREDITARY, SPATIAL REARRANGEMENT OF ANTIGEN COMPLEXES, IN THE
      INFLUENZA VIRUS.
AB  - During passage in mice which had been vaccinated with the homologous, and with
      closely related strains of influenza virus, the passage strain developed a
      lessened susceptibility to the deleterious effects of the "immune" environment,
      concommittant with which was a developed capacity to evoke antibodies which
      reacted with earlier strains of virus-a capacity which was inapparent in the
      parent strain. However, the parent strain exhibited a relatively broad range of
      surface reactivity which was not apparent in the derived strain. The data are
      interpreted to mean that the hereditary change resulted from spatial
      rearrangement and quantitative redistribution of antigens in the virus particle
      (in which the surface is viewed as being distinct from the inner bulk), and are
      viewed as enhancing the idea that influenza virus variation (i.e., "mutation")
      may result from a rearrangement of existing hereditary elements.

PMID- 19867195
TI  - SITES OF FORMATION OF IMMUNE GLOBULINS AND OF A COMPONENT OF C'(3): I. A NEW
      TECHNIQUE FOR THE DEMONSTRATION OF THE SYNTHESIS OF INDIVIDUAL SERUM PROTEINS BY
      TISSUES IN VITRO.
AB  - The development of a new method for the determination of the sites of serum
      protein formation has been described. The method involves the incorporation of
      C(14)-labeled amino acids by tissues cultured in vitro, and subsequent
      autoradiography of immunoelectrophoretic patterns prepared from a mixture of
      culture fluids and carrier serum with an antiserum against the carrier serum.
      This technique has been used to demonstrate formation of gamma-globulin, of
      beta(2)-macroglobulin, and of a component of C'(3) by mouse spleen tissue, and of
      various other serum proteins by liver tissue. The specificity and sensitivity of
      this method have been discussed, and some of its advantages and pitfalls were
      mentioned. In addition, a rabbit antimouse serum was prepared, and the
      immunoelectrophoretic patterns obtained with mouse serum were compared with those
      described in the literature.

PMID- 19867196
TI  - SITES OF FORMATION OF IMMUNE GLOBULINS AND OF A COMPONENT OF C'(3): II.
      PRODUCTION OF IMMUNOELECTROPHORETICALLY IDENTIFIED SERUM PROTEINS BY HUMAN AND
      MONKEY TISSUES IN VITRO.
AB  - Human, and monkey tissues were cultured in the presence of labeled amino acid.
      The culture fluids were then examined for labeled serum proteins by means of
      autoradiography of immunoelectrophoretic patterns prepared from mixtures of the
      fluids and carrier sera. Gamma globulin, beta(2A)-globulin, beta(2M)globulin, and
      beta(1C)-globulin were found to be formed in human lymph node, bone marrow, and
      ileum. Gamma globulin, beta(2M)-globulin, and beta(1C)-globulin were found to be
      formed in monkey spleen, lymph node, and bone marrow. Formation of several other
      serum proteins was observed in the monkey liver.

PMID- 19867197
TI  - INDUCTION OF TUMORS IN DOMESTIC RABBITS WITH NUCLEIC ACID PREPARATIONS FROM
      PARTIALLY PURIFIED SHOPE PAPILLOMA VIRUS AND FROM EXTRACTS OF THE PAPILLOMAS OF
      DOMESTIC AND COTTONTAIL RABBITS.
AB  - A deoxyribonucleic acid preparation which showed infectivity and tumorigenic
      activity in domestic rabbits was isolated from the papillomatous tissue of wild
      cottontail rabbits by phenolic deproteinization procedure. The activity of the
      preparation could be completely abolished by its exposure to a minute amount
      (0.02 microg/ml) of DNAase. Antisera against Shope papilloma virus did not block
      the tumorigenic activity of the preparation, and trypsin and chymotrypsin had no
      effect on it. The extraction with phenol of a partially purified virus
      preparation also yielded extracts with tumorigenic potency. Extracts obtained
      from the domestic rabbit papilloma and submitted to phenolic deproteinization
      also proved infective and tumorigenic in rabbits of this sort, although the level
      of "tumorigenicity" was much lower than that of the cottontail preparations.
      Tests for intact virus, carried out with half of the extracts yielded wholly
      negative findings.

PMID- 19867198
TI  - A LABILE SERUM FACTOR IN EXPERIMENTAL ENDOTOXIN SHOCK: CROSS-TRANSFUSION STUDIES
      IN DOGS.
AB  - Peripheral vascular failure caused by endotoxin in the dog has an initial stage
      of vasoconstriction. Preliminary studies in vitro demonstrated that the
      constriction was due to the interaction of endotoxin with a heat-labile serum or
      plasma factor and platelets, resulting in the liberation of histamine. Further
      studies on the intact dog support and extend this concept. A standardized dose of
      Escherichia coli endotoxin produced fatal shock in control adult mongrel dogs
      within 28 hours. The characteristic pattern of changes included progressive
      hypotension, oliguria and anuria, hemoconcentration, and acidosis. Normal dogs
      were protected against endotoxin by transfusions of blood in which the essential
      serum factor was depleted in one of two ways. First, plasma separated from the
      blood of normal animals was heated at 56 degrees C for 30 minutes, and the
      infused reconstituted whole blood protected normal dogs. Protection was not
      afforded by unheated reconstituted blood. Second, blood from immune dogs obtained
      within 24 hours after a second lethal dose of endotoxin protected recipient dogs.
      However, protection was not demonstrated with blood collected 72 hours after a
      second injection of endotoxin. The nature of the serum factor essential for
      endotoxin activity is not known. It is postulated that an enzyme or enzyme system
      is involved, and the possible role of complement is discussed.

PMID- 19867200
TI  - ANTIGENIC RELATIONSHIPS BETWEEN IMMUNE GLOBULINS AND CERTAIN RELATED PARAPROTEINS
      IN MAN.
AB  - The antigenic properties of normal 19S gamma-globulin, pathologic macroglobulins,
      beta(2A)-myeloma proteins, and Bence Jones proteins have been compared with 7S
      gamma-globulin and the small 3.5S units derived from it by gel diffusion
      precipitin techniques. These studies demonstrate that the determinant groups on
      the 7S gamma-globulin molecule responsible for the cross-reaction with each of
      the other proteins are associated with the two fragments of 7S gamma-globulin
      which have the antibody-combining sites. The antigenic specificity of the 7S
      gamma-globulin which distinguishes it from each of these proteins is associated
      primarily with the fragment that is richest in hexose and can not combine with
      antigen. However when compared with certain of the paraproteins additional
      antigenic specificity was also found to reside in the fragments with antibody
      combining activity. The finding of similar antigenic relationships in rabbit
      gamma-globulins suggests that some of the biological properties associated only
      with the 7S gamma-globulins and not with the other immune globulins may reside in
      the fragment which also carries the antigenic specificity of the protein.

PMID- 19867199
TI  - THE ROLE OF HUMORAL ANTIBODIES IN REJECTION OF SKIN HOMOGRAFTS IN RABBITS : I.
      PASSIVE TRANSFER OF ISOIMMUNE SERUM TO CONDITIONED HOSTS.
AB  - Gross and microscopic observations of skin homograft rejection carried out in
      cortisone-conditioned and non-conditioned rabbits seem to indicate that humoral
      antibodies play an important role in the phenomenon. Thus, local administration
      of isoimmune serum to animals bearing skin homografts resulted in a significantly
      earlier rejection of that particular test graft without modifying the course of a
      neighboring control-skin graft. This result appears to support the idea that
      homograft rejection is not only due to cellular antibodies but to a combination
      of both humoral and cellular immune responses, which should not be regarded as
      completely unrelated.

PMID- 19867201
TI  - STUDIES ON THE PATHOGENESIS OF ACUTE INFLAMMATION : III. THE FAILURE OF
      ANTICOAGULANTS TO PREVENT THE LEUCOCYTIC STICKING REACTION AND THE FORMATION OF
      SMALL THROMBI IN RABBIT EAR CHAMBERS DAMAGED BY HEAT.
AB  - Vigorous anticoagulation with heparin sodium and sodium warfarin singly and in
      combination did not prevent the margination and endothelial sticking reaction of
      leucocytes in rabbit ear chambers damaged by heat. The general inflammatory
      reaction observed in this preparation was similarly uninfluenced by the
      anticoagulants. An unexpected finding after administration of heparin was the
      enhanced formation of platelet and fibrin-like thrombi within damaged ear
      chambers. Sodium warfarin did not induce or prevent this heparin effect.
      Production of these heparin-associated thrombi was minimized in animals subjected
      to defibrinogenation in vivo whereas leucocytic sticking was not modified.
      Although defibrinogenation was not absolute, these experiments represent
      additional proof that the sticking of white blood cells to vascular endothelium
      is not causally related to the fibrinogen-fibrin system.

PMID- 19867202
TI  - THE BEHAVIOR OF THREE DIFFERENT KINDS OF ANTIBODIES IN TUBERCULOSIS: ANTIPROTEIN,
      ANTIPOLYSACCHARIDE, AND ANTIPHOSPHATIDE : I. EXPERIMENTAL TUBERCULOSIS.
AB  - The mode and the level of production of the three different kinds of antibodies,
      antipolysaccharide, antiprotein, and antiphosphatide, were found to differ
      considerably with the mode of infection and the virulence of tubercle bacilli.
      Evidence is given that production of the antipolysaccharide and antiprotein is
      stimulated without regard to the mode of infection and the virulence of bacilli,
      while the antiphosphatide is produced chiefly under conditions where in vivo
      bacilli might have undergone destruction. Of the three antibodies, the level of
      antiphosphatide was shown to reflect most faithfully the progression of
      experimental tuberculous infection. The amounts of the three circulating
      antibodies were found to have no direct relationship to the degree of tuberculin
      skin hypersensitivity.

PMID- 19867203
TI  - THE BEHAVIOR OF THREE DIFFERENT KINDS OF ANTIBODIES IN TUBERCULOSIS: ANTIPROTEIN,
      ANTIPOLYSACCHARIDE, AND ANTIPHOSPHATIDE : II. HUMAN TUBERCULOSIS.
AB  - In human tuberculosis as in experimental tuberculosis, there exist in the serum
      of tuberculous patients three different kinds of antibodies completely distinct
      from each other, antipolysaccharide, antiprotein, and antiphosphatide. The two
      former antibodies are produced whenever tuberculous infection takes place or
      exists and they persist for a long period, even though tuberculous disease be
      arrested. On the contrary, the production of the antiphosphatide seems to be
      mainly conditioned by the outbreak of tuberculous disease following infection,
      because none of the tuberculin-positive healthy persons tested gave a positive
      phosphatide hemagglutination test. The antiphosphatide hemagglutination test
      furnishes useful information about the extent or the activity of tuberculous
      disease. No correlation was noticed between the degree of tuberculin skin
      hypersensitivity and the amount of any of the three antibodies. The usefulness of
      the phosphatide hemagglutination test in the diagnosis of tuberculosis is
      discussed.

PMID- 19867204
TI  - CHANGES IN CONNECTIVE TISSUE AND INTESTINE CAUSED BY VITAMIN A IN AMPHIBIA, AND
      THEIR ACCELERATION BY HYDROCORTISONE.
AB  - In view of the theory that an excess of vitamin A causes release of cathepsins
      from intracellular lysosomes, hypervitaminosis A was induced orally in the larvae
      of Xenopus laevis. It was predicted that the tails of these amphibia would
      undergo resorption prior to metamorphosis, since the presence of abundant
      lysosomes, associated with measurable increases of catheptic activity, had
      previously been demonstrated in the resorbing tails of amphibia during
      metamorphosis. This prediction was confirmed; after 3 to 4 weeks of
      hypervitaminosis A, the tails of treated animals underwent partial resorption.
      Other transitory appendages, the rostral tentacles, collapsed after 2 weeks of
      treatment with an excess of vitamin A, an effect analogous to the collapse of
      rabbits' ears after intravenous papain. These effects were related to the loss of
      metachromatic extracellular material in these appendages. Excess of vitamin A
      caused kyphoscoliosis and prognathos in the larvae. The hypervitaminotic larvae
      always developed a mucinous diarrhea, which was associated with a remarkable
      overgrowth of metachromatic goblet cells of the intestine. The entire intestine
      of the treated animals was more advanced in development than that of control
      larvae at equivalent stages. All the effects of hypervitaminosis A were
      accelerated by the simultaneous administration of hydrocortisone. This was held
      to be due to liberation of vitamin A from hepatic stores by the steroid, and is
      in contrast to the retardation of hypervitaminosis A by hydrocortisone in vitro.

PMID- 19867205
TI  - COMPLEMENT FIXATION IN DISEASED TISSUES : I. FIXATION OF GUINEA PIG COMPLEMENT IN
      SECTIONS OF KIDNEY FROM HUMANS WITH MEMBRANOUS GLOMERULONEPHRITIS AND RATS
      INJECTED WITH ANTI-RAT KIDNEY SERUM.
AB  - An immunohistologic complement fixation test has been used in an effort to detect
      immune complexes in sections of kidney from rats injected with rabbit anti-rat
      kidney serum and in sections of biopsied kidneys from four humans with membranous
      glomerulonephritis. Sections of the rat and human kidneys were treated with
      fluorescein-conjugated anti-rabbit globulin or antihuman globulin respectively.
      Adjacent sections in each case were incubated first with fresh guinea pig serum
      and then in a second step were treated with fluorescein-conjugated antibodies
      against fixed guinea pig complement to detect sites of fixation of the
      complement. It was demonstrated that the sites of rabbit globulin in glomerular
      capillary walls of the rat kidneys and the sites of localized human globulin in
      thickened glomerular capillary walls and swollen glomerular endothelial cells of
      the human kidneys were the same sites in which guinea pig complement was fixed in
      vitro. It was concluded from these studies that rabbit nephrotoxic antibodies
      localize in rat glomeruli in complement-fixing antigen-antibody complexes.
      Furthermore, it was concluded that the deposits of human globulin in the
      glomeruli of the human kidneys behaved like antibody globulin in complement
      fixing antigen-antibody complexes. The significance of demonstrating complement
      fixing immune complexes in certain diseased tissues is discussed in regard to
      determination of the causative role of allergic reactions in disease.

PMID- 19867206
TI  - EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM : IV. RENAL FUNCTION AND
      ADRENOCORTICAL ACTIVITY AS FACTORS IN THE NITROGEN EXCRETION ASSAY FOR ENDOTOXIN.
AB  - In vitro secretion of glycocorticoids by adrenal glands pooled from several
      control mice was compared with that of glands removed from animals following
      injections of either ACTH or endotoxin. Both substances prevent glycocorticoid
      synthesis stimulated in vitro with ACTH. Cholesterol content of adrenal glands
      under these conditions was nearly depleted, indicating maximal response to ACTH
      or endotoxin prior to their removal for the in vitro tests. In an effort to
      account physiologically for the manner in which endotoxin suppresses or prevents
      the rise in urinary nitrogen excreted in response to ACTH, blood non-protein
      nitrogen levels (NPN) were determined. The following experimental conditions
      resulted in increased urinary nitrogen excretion but did not alter blood NPN:
      cortisone given alone or at the same time as endotoxin; ACTH alone;
      dichloroisoproterenol (DCI) given concurrently with endotoxin; and lactalbumin
      digest injected intraperitoneally. Increases (2- to 3-fold) in blood NPN were
      observed when endotoxin was given alone, concurrently with ACTH, or 3 hours prior
      to cortisone, DCI, or lactalbumin digest. Urinary nitrogen excretion showed no
      change under these conditions. The elevation in blood NPN in endotoxin-poisoned
      mice was found to be due almost entirely to urea nitrogen and not to amino acid
      nitrogen or to other nitrogenous wastes. Blood clearance of mulin, phenol red
      excretion, and urea elimination were each determined in control and in endotoxin
      poisoned mice. The latter mice showed impaired renal function. Treatment with
      diuretics (diuril and aminophylline) failed to alter oliguria or elevated blood
      NPN. Hydergine treatment was also without effect. Total carcass NPN and urinary
      nitrogen excretion data were combined to give a picture of total protein
      catabolized by mice under different experimental conditions. Cortisone injected
      at the same time as endotoxin or 3 hours later resulted in the same increase in
      total NPN. However, in the former case all the extra nitrogen appeared in the
      urine while in the latter it remained in the carcass. ACTH given alone or
      concurrently with endotoxin produced large increases in total NPN but less in
      poisoned mice. This suggests that endotoxin suppresses adrenal response to ACTH.
      Urea injected into normal mice was recovered quantitatively in urine while in
      endotoxin-poisoned mice it was partitioned between carcass and urine. Elevation
      of carcass NPN by means of urea injections failed to alter the lethality of an
      LD(70) dose of endotoxin.

PMID- 19867207
TI  - THE APPLICATION OF FERRITIN-CONJUGATED ANTIBODY TO ELECTRON MICROSCOPIC STUDIES
      OF INFLUENZA VIRUS IN INFECTED CELLS : I. THE CELLULAR SURFACE.
AB  - Immersion of chorioallantoic membranes infected by influenza virus in ferritin
      conjugated antibody globulin prior to fixation permits recognition of viral
      antigen at the cellular surface. In some cases the antigen is confined to sites
      at which viral particles appear to be in process of release, whereas in others it
      is present along the entire cellular surface. During infection part or all of the
      cellular membrane presumably is transformed so that it contains the antigenic and
      structural components which coat the virus during emergence. It is suggested that
      detached fragments of cytoplasm possessing surface hemagglutinin but incapable of
      initiating infection constitute at least one form of "incomplete virus."

PMID- 19867208
TI  - THE APPLICATION OF FERRITIN-CONJUGATED ANTIBODY TO ELECTRON MICROSCOPIC STUDIES
      OF INFLUENZA VIRUS IN INFECTED CELLS : II. THE INTERIOR OF THE CELL.
AB  - Freezing of the chorioallantoic membrane after brief fixation in formalin
      preserves antigenicity of cellular components and allows penetration of ferritin
      conjugated antibody. Dense aggregates of viral antigen, presumed to be of the
      soluble type, were found in the nuclei of cells infected with influenza virus.
      Intracytoplasmic antigen, on the other hand, was widely dispersed. The
      experimental observations are consistent with the hypothesis that soluble antigen
      diffuses into the cytoplasm through intact nuclear membranes. Nucleoli do not
      appear to be the sites of antigen synthesis.

PMID- 19867209
TI  - SENSITIZATION TO DENATURED AUTOLOGOUS GAMMA GLOBULIN.
AB  - Immunization of guinea pigs with denatured autologous gamma globulin results in
      the development of delayed hypersensitivity to some form of gamma globulin. When
      the autologous gamma globulin is subjected to denaturation with alkaline
      treatment as employed in this study, guinea pigs regularly develop reactivity to
      the immunizing material and occasionally to some form of heterologous gamma
      globulin. With other forms of denaturation, such as produced by urea, ultrasound,
      or heat, guinea pigs rarely develop sensitivity to the immunizing material but
      frequently exhibit delayed reactivity to native or denatured heterologous gamma
      globulin. Reactivity against native autologous gamma globulin does not occur.
      Guinea pigs immunized with undenatured autologous gamma globulin fail to develop
      reactivity to any form of gamma globulin. Rabbits immunized with denatured
      autologous gamma globulin develop circulating antibodies against some form of
      gamma globulin. Rabbits immunized with alkaline denatured autologous gamma
      globulin develop antibodies against the preparation used for immunization and
      against heterologous gamma globulin; rabbits immunized with autologous gamma
      globulin subjected to freeze-thaw or heat denaturation develop antibodies against
      heterologous globulin, but antibodies against the immunizing material can only
      rarely be demonstrated.

PMID- 19867210
TI  - IMMUNOHISTOLOGIC STUDIES ON ANTIGEN-ANTIBODY REACTIONS IN THE AVASCULAR CORNEA :
      I. REACTIONS IN RABBITS ACTIVELY SENSITIZED TO FOREIGN PROTEIN.
AB  - The injection of antigen into the center of the avascular cornea of homologously
      sensitized animals induced a ring of opacification between the center of the
      cornea and the limbus. This ring of opacification was composed of a line of
      deeply eosinophilic amorphous material in a matrix of swollen collagen fibers,
      palisaded by polymorphonuclear leucocytes. By use of fluor-tagged antigen, it was
      shown that the line of damage in the cornea coincided with the precipitation of
      antigen presumably by antibody entering the cornea from the limbal vessels. With
      the passage of time, the antigen-antibody precipitates were removed, at least in
      part by phagocytosis, and the ring of opacification was replaced by ingrowing
      blood vessels surrounded by plasma cells. Treatment of sensitized animals with
      nitrogen mustard showed that antigen-antibody interaction could injure the
      corneal stroma in the relative absence of polymorphonuclear leucocytes.

PMID- 19867211
TI  - THE HISTOLOGICAL DISTRIBUTION OF THE BLOOD GROUP SUBSTANCES IN MAN AS DISCLOSED
      BY IMMUNOFLUORESCENCE : II. THE H ANTIGEN AND ITS RELATION TO A AND B ANTIGENS.
AB  - The H antigen was mapped out by immunofluorescence in human tissues (including
      those of fetuses from 15 cm crown-heel length) from individuals of the various
      groups within the ABO system, both secretors and non-secretors. The distribution
      of the antigen can be summarized under the following headings: Cell walls of
      endothelium: present throughout the cardiovascular system; Cell walls of
      stratified epithelia: in skin, non-cornifying squamous stratified membranes,
      transitional epithelia; Mucus: occurring wherever the latter is produced in
      secretor individuals and confined to a few special topographical areas in non
      secretors; Secretions and excretions: the pancreatic and sudoriferous
      (independent of secretor status), and mammary and uterine (governed by the
      secretor makeup) all contain it. The distribution of the H antigen is most fully
      represented in tissues of group O. It follows an over-all universal pattern,
      characteristically modified in non-secretors, equally valid for antigens A and B
      described in a preceding study. Within this pattern, in tissues of the non-O
      groups, the complement of the H substance in its various forms wanes in a manner
      consistent with the hypothesis that it serves as a substrate for the A(1), A(2),
      B genes, exerting their action with different degrees of efficiency. The
      secretor:non-secretor phenomena can be most simply interpreted by viewing the non
      secretor, recessive gene (in the homozygous, ss condition) as inhibiting the
      production of some of the water-soluble forms of the blood group substances.
      Since the gene was never found responsible for dissociation of the H and A, B
      antigens its inhibitory action is thought to be wrought at the point of formation
      of the basic H substance or its precursor.

PMID- 19867212
TI  - THE CHARACTERIZATION OF STAPHYLOCOCCAL TOXINS : II. THE ISOLATION AND
      CHARACTERIZATION OF A HOMOGENEOUS STAPHYLOCOCCAL PROTEIN POSSESSING ALPHA
      HEMOLYTIC, DERMONECROTIC, LETHAL, AND LEUCOCIDAL ACTIVITIES.
AB  - The continuous flow paper electrophoretic methods used to isolate alpha hemolysin
      are presented. The purity of the alpha hemolysin preparation is demonstrated by
      double agar diffusion, immunoelectrophoretic, and ultracentrifugation techniques.
      Indirect evidence of purity is provided by the fact that rabbit immunized with
      purified alpha hemolysin produced detectable antibody only to alpha hemolysin.
      Direct support is given to the "unitarian theory" by the demonstration that
      purified alpha hemolysin also possessed dermonecrotic, lethal, and leucocidal
      activities. Further studies dependent on the availability of purified alpha
      hemolysin are outlined.

PMID- 19867213
TI  - STUDIES OF THE GENERALIZED SHWARTZMAN REACTION PRODUCED BY DIET : I. PATHOLOGY.
AB  - The generalized Shwartzman reaction can be produced in pregnant rats by dietary
      means in the absence of injection of exogenous bacterial endotoxin. The
      experiment consists of a period of exposure to a diet low in tocopherol followed
      by exposure to a diet containing oxidized lipids during the gestation period.
      Pregnancy near term is an essential requirement for the development of the
      generalized Shwartzman reaction in these experiments. Fibrin thrombi were found
      in the renal glomeruli in 88.5 per cent, in the lungs in 94.2 per cent, in the
      liver in 11.4 per cent, in the spleen in 11.4 per cent, and in the adrenal in 40
      per cent of animals that died spontaneously. There were pathologic alterations in
      the placenta which consisted of degeneration of the trophoblast, thrombosis of
      maternal blood channels in the giant cell trophoblast layer and in the labyrinth,
      congestion of the labyrinth, hemorrhage into the uterine cavity, placental
      separation, intra-uterine fetal death, decidual and uterine vein thrombosis, and
      placentitis in 10 per cent of the cases. The mechanism by which the diet is
      instrumental in causing this reaction remains to be demonstrated.

PMID- 19867214
TI  - STUDIES OF THE GENERALIZED SHWARTZMAN REACTION PRODUCED BY DIET : III. PARTIAL
      PREVENTION BY ANTIBIOTICS.
AB  - A 4-fold reduction in the death rate of pregnant rats subjected to a diet capable
      of inducing the generalized Shwartzman reaction was obtained by the
      administration of oral absorbable and non-absorbable antibiotics. The possible
      mechanisms of this partial protection have been discussed.

PMID- 19867215
TI  - COMPARATIVE STUDIES IN ROUS SARCOMA WITH VIRUS, TUMOR CELLS AND CHICK EMBRYO
      CELLS TRANSFORMED IN VITRO BY VIRUS : III. MALIGNANCY IN VIVO OF CELLS
      TRANSFORMED IN VITRO BY VIRUS.
AB  - Chick embryo fibroblasts infected with Rous sarcoma virus in vitro are rendered
      malignant for such cells produce typical Rous sarcomas when injected into
      susceptible chicks since the tumors produced predominantly retain the sex
      chromatin patterns of the donor cells when such cells are injected into a
      recipient of the opposite sex. However, examination of the sex chromatin of cells
      at the periphery of the tumor shows presence of recipient cells though the bulk
      of the tumor is clearly of donor cell origin. Such tumors grow and cause death of
      the recipient. Injection of RSV induces tumors of the sex of the recipient as
      also does the injection of transformed cells rendered incapable of multiplication
      by x-rays. Following their injection into susceptible chicks, the cells
      transformed in vitro by virus behave in the same manner as tumor cells obtained
      from tumors induced by virus in vivo and cultivated in the same conditions in
      vitro. When such tumors induced by transformed cells are serially transferred in
      recipients of the opposite sex, they gradually convert to the sex of the
      recipient indicating that the tumors are not indefinitely transplantable. These
      chick embryo fibroblasts transformed in vitro show the same neo-plastic
      properties as tumor cells when they are introduced into the cheek pouch of the
      hamster or the eye of the guinea pig.

PMID- 19867216
TI  - THE INTRACELLULAR DISTRIBUTION OF GAMMA GLOBULIN IN A MOUSE PLASMA CELL TUMOR
      (X5563) AS REVEALED BY FLUORESCENCE AND ELECTRON MICROSCOPY.
AB  - Ferritin- and fluorescein-conjugated antibody staining has been applied to a
      study of a mouse plasma cell tumor. The presence of myeloma globulin within
      cisternae of the endoplasmic reticulum was observed at a stage of the secretory
      process when the remainder of the cytoplasm was essentially free of labeled
      globulin. The distribution of ferritin suggested a functional heterogeneity among
      units of the endoplasmic reticulum. Apparently, progressive accumulation of
      globulin results in distension of the endoplasmic reticulum and, occasionally, in
      the appearance of considerable quantities of this secretory protein in the
      extracisternal cytoplasmic matrix. Participation of the Golgi apparatus in the
      packaging and release of small quantitites of globulin seems likely. In addition,
      however, fragmentation of the peripheral cytoplasm with rupture of distended
      ergastoplasmic vesicles appeared to be another pathway whereby globulin is
      secreted.

PMID- 19867217
TI  - STRUCTURE AND DEVELOPMENT OF VIRUSES AS OBSERVED IN THE ELECTRON MICROSCOPE :
      VII. INCOMPLETE INFLUENZA VIRUS.
AB  - Chicken embryos were infected by the chorioallantoic route with influenza virus,
      PR8 strain, in the form of undiluted chorioallantoic fluid. Electron microscopic
      examination 24 hours after infection revealed that membrane-bound fragments of
      cytoplasm appeared to be in process of release from entodermal cells of the
      chorioallantois. The number of such fragments was greatly increased in proportion
      to the number of typical viral particles after the third serial passage, which
      was accompanied by a reduction of the infectivity-hemagglutinin ratio (von Magnus
      effect). The lack of recognizable internal components, together with the presence
      of surface structure which closely resembled that of the virus and frequently
      contained viral antigen, suggested that many of these fragments were incomplete
      viral particles. It is proposed that concentrated inocula damage the cells and
      interfere with differentiation of the virus, but do not inhibit formation and
      detachment of cytoplasmic processes. Under these circumstances the accumulation
      of viral antigen at the surface of the cell will result in the predominant
      formation of incomplete virus.

PMID- 19867218
TI  - CLASSIFICATION OF MYELOMA PROTEINS, BENCE JONES PROTEINS, AND MACROGLOBULINS INTO
      TWO GROUPS ON THE BASIS OF COMMON ANTIGENIC CHARACTERS.
AB  - Antisera to normal 7S gamma-globulin and to Bence Jones proteins permit the
      grouping of myeloma proteins (gamma and beta 2A types), Bence Jones proteins, and
      the Waldenstrom type macroglobulins into two fundamental antigenic groups. The
      antigenic determinants responsible for this grouping are common to all these
      proteins which fall in the general category of immunoglobulins. Antisera to Bence
      Jones proteins were particularly useful for this classification since they failed
      to react with the proteins of the opposite group. These antisera also permit the
      grouping of normal 7S gamma-globulin into two major types. The Bence Jones
      proteins from individual patients were found to correspond in antigenic group to
      that of the serum myeloma protein. Studies with antisera to 7S gamma-globulin and
      to Bence Jones proteins indicated that the Bence Jones proteins were
      antigenically identical to a portion of the corresponding multiple myeloma
      protein molecules.

PMID- 19867219
TI  - EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM : V. THE HYPERREACTIVITY OF MICE
      INFECTED WITH MYCOBACTERIUM TUBERCULOSIS, STRAIN BCG.
AB  - The greater susceptibility to the lethal effects of bacterial endotoxin (heat
      killed Salmonella typhimurium or Escherichia coli lipopolysaccharide, in mice
      infected with an attenuated strain of Mycobacterium tuberculosis (BCG) was
      confirmed. It reached a maximum at 2 weeks postinfection and gradually diminished
      for an additional 6 weeks. At the time of maximum susceptibility several
      metabolic and physiological differences became apparent. BCG-infected mice die
      sooner (4 to 12 hours) and without the diarrhea, conjunctivitis, and general
      symptomatology associated with endotoxin deaths of normal animals.
      Reticuloendothelial blockade results in only a small change in reactivity to
      endotoxin, in contrast to normal mice. Subcutaneous injection of 2 units of ACTH
      is followed by no significant increase in urinary nitrogen excretion while in
      control animals it more than doubles. Plasma clearance of intravenously
      administered inulin is approximately normal in BCG-infected mice 17 hours after
      an LD(50) dose of endotoxin but control mice similarly treated show renal
      impairment. In line with this result is the absence of elevated carcass non
      protein nitrogen (NPN) following endotoxin poisoning or at the moment of death
      from endotoxemia in the hyperreactive animals in contrast to the two- to
      threefold increase in carcass NPN in normal mice under similar conditions. Body
      carbohydrate is at a minimum and becomes depleted to a level approximating that
      found at death more rapidly in BCG-infected mice given endotoxin than in
      controls. There is also a lower ratio of carbohydrate anabolized to protein
      catabolized following cortisone administration to BCG-infected mice than in
      control mice. This is found in adrenalectomized mice and in stressed animals and
      is reported elsewhere. Some of the differences just described can be attributed
      to a refractory adrenal cortex. There is less depletion of adrenal cholesterol in
      vivo and lower corticoid synthesis in vitro than in normal mice yet this is not
      fundamentally responsible for the greater susceptibility of BCG-infected animals
      to endotoxin since adrenalectomized mice, which are even more susceptible, are
      metabolically and physiologically more comparable to normal mice than to BCG
      infected mice. One can conclude, therefore, that the hyperreactivity of BCG
      infected mice is more than an intensification of the normal response to
      endotoxin.

PMID- 19867220
TI  - THE MODE OF ACTION OF ANTIBIOTICS IN STIMULATING GROWTH OF CHICKS.
AB  - A study was made of the effect of antibiotics on growth of chicks and on
      intestinal absorption of fats and carbohydrates. Around the 8th day of life,
      chicks fed an antibiotic-free casein-sucrose diet developed a transitory syndrome
      of malabsorption of fats and carbohydrates, associated with disturbance of the
      efficiency of feed utilization and poor weight increase. Administration of
      virginiamycin, at a level of 20 ppm, suppressed this period of malabsorption and
      resulted in improved feed conversion and increased weight gain. The temporary
      growth depression and malabsorption were not observed in disinfected rooms in new
      quarters. Under these conditions virginiamycin did not stimulate growth nor was
      the efficiency of feed utilization improved by the antibiotic. However, the
      growth-depressing flora could be introduced to the new quarters by feeding each
      bird 50 mg of fresh feces collected from chicks in old quarters. Both the
      intestinal absorption and the growth-promoting effect of virginiamycin were
      influenced by the type of carbohydrate in the basal diet, and have been found to
      be most pronounced when sucrose was fed as the sole source of carbohydrate. The
      malabsorption was less obvious when cornstarch was substituted for sucrose. In
      this case virginiamycin had only a limited effect on growth and on feed
      conversion. The present investigations suggest that antibiotics stimulate growth
      of chicks by their antibacterial action against Gram-positive microorganisms
      which interfere with the absorption of nutrients. Furthermore, the growth
      promoting effect seems to be most pronounced during a limited period of a few
      days around the 8th day of life.

PMID- 19867221
TI  - ISOLATION AND PROPERTIES OF A GROUP ANTIGEN OF STAPHYLOCOCCUS ALBUS.
AB  - An antigen composed of glycerophosphate and glucose has been isolated from the
      cell walls of a strain of Staphylococcus albus. The antigen reacted with
      homologous and heterologous S. albus antisera. Similar material was isolated from
      the cell walls of three other S. albus strains. The antigen did not react with S.
      aureus antiserum nor with normal human or rabbit serum. The antigen appeared to
      have a backbone structure of glycerophosphate with appended monoglucoside units.
      The antigenic determinant was shown to be glucose in alpha linkage.

PMID- 19867222
TI  - TWO MAJOR TYPES OF NORMAL 7S gamma-GLOBULIN.
AB  - Normal 7S human gamma-globulin was found to contain two fundamental antigenic
      groups of molecules. The group 1 molecules of normal gammaglobulin correspond
      antigenically to group 1 multiple myeloma proteins and Bence Jones proteins; and
      group 2 molecules of normal gamma-globulin correspond antigenically to group 2
      multiple myeloma proteins and Bence-Jones proteins. Among pooled human Fr II and
      several individual gamma-globulin preparations, approximately 60 per cent of
      molecules belong to group 1 and approximately 30 per cent of molecules to group 2
      in this classification. The possible existence of a third minor antigenic group,
      constituting about 10 per cent, is discussed. Antisera to Bence Jones proteins of
      antigenic group 1 and group 2, in conjunction with I-131-labeled 7S gamma
      globulin proved to be the most useful system for defining the antigenic groups of
      normal gamma-globulin. The group-specific antigenic determinants of normal 7S
      gamma-globulin molecules were located on the S fragments of these proteins.

PMID- 19867223
TI  - THE EFFECT OF ANTIBACTERIAL DRUGS ON THE FECAL FLORA OF MICE.
AB  - Oral administration of penicillin, terramycin, or chloramphenicol to NCS mice
      rapidly brought about profound changes in their fecal flora. The lactobacilli
      disappeared completely, whereas the numbers of enterococci and Gram-negative
      bacilli reached very high levels. In contrast, no effect on the fecal flora could
      be detected following administration of isoniazid in any amount. The intensity
      and duration of the effects on the fecal flora were related to the type of drug
      and to the amount of it administered. Chloramphenicol produced disturbances which
      were less profound and of shorter duration than those produced by penicillin or
      terramycin. The duration of the disturbances in the fecal flora produced by
      antibacterial drugs was markedly conditioned by the nutritional regimen. The
      fecal flora returned to its pretreatment state (large numbers of lactobacilli,
      few enterococci, and few Gram-negative bacilli) within less than 4 weeks after
      discontinuing the drug when the mice were fed a complex diet of ill defined
      composition (commercial pellets). Contrariwise, the fecal flora remained markedly
      different from that of control mice when the animals were fed semisynthetic diets
      containing as source of protein either 15 per cent casein or 15 per cent wheat
      gluten (both supplemented with cystine); or 15 per cent wheat gluten supplemented
      with lysine, threonine, and cystine. The fecal flora of mice treated with
      penicillin contained large numbers of lactose-fermenting Gram-negative bacilli,
      not found in the untreated animals. These lactose fermenters persisted for
      several months after discontinuance of the drug in mice fed either the casein or
      gluten diets, but they disappeared rapidly from mice fed pellets. Similar
      results, although less striking, were obtained with Swiss mice from colonies
      maintained under usual conditions, and therefore having a fecal flora more
      complex than that of NCS mice.

PMID- 19867224
TI  - THE EFFECT OF ANTIBACTERIAL DRUGS ON THE WEIGHT OF MICE.
AB  - NCS mice gained weight rapidly when fed a gluten diet deficient in several amino
      acids, but their weight gain on the same regimen was very much retarded if they
      were given antibacterial drugs, even for a short period of time. This retardation
      of growth could not be entirely corrected by supplementing the gluten diet with
      lysine and threonine. The decrease in growth rate brought about by antibacterial
      drugs could probably be traced to the alteration in intestinal flora resulting
      from drug treatment. The intensity and duration of both types of changes were
      related to the dose of drug administered, and to the length of the treatment
      period. Whatever the nutritional regimen, treatment with penicillin caused a
      retardation of weight gain in NCS mice. The retardation was more pronounced, and
      longer lasting, when the animals were fed semisynthetic regimens (containing
      casein or gluten) than when they were fed crude diets (pellets) containing
      natural materials of ill defined composition. These differences probably had
      their origin in the fact that the changes in fecal flora induced by the drugs
      were profoundly influenced by the composition of the diet. Antibacterial drugs
      which retarded weight gain of Swiss NCS mice, in contrast increased weight gain
      in ordinary Swiss mice raised under usual conditions. It is probable that this
      difference in response to the antibacterial drugs resulted from the fact that
      ordinary Swiss mice have a much more complex intestinal flora than NCS animals.

PMID- 19867225
TI  - THE ANTIBODY RESPONSE OF RATS DEPLETED OF LYMPHOCYTES BY CHRONIC DRAINAGE FROM
      THE THORACIC DUCT.
AB  - The chronic drainage of lymph and cells from a thoracic duct fistula in rats
      results in a reduction in the weight of all the lymph nodes and of their content
      of small lymphocytes. The primary immune response to tetanus toxoid or sheep
      erythrocytes is severely depressed or abolished in such animals. This
      unresponsive state is related to the loss of lymphocytes from the thoracic duct
      fistula and, not to stress factors ensuing from the trauma of operation and
      restraint; it can be reversed by injecting inocula which contain almost
      exclusively small lymphocytes. In contrast to the severe impairment of the
      primary immune response in lymphocyte-depleted rats, such animals show a normal
      response to a second injection of tetanus toxoid. The mechanism by which small
      lymphocytes mediate the primary immune response is discussed.

PMID- 19867226
TI  - FURTHER STUDIES ON IMMUNITY IN EXPERIMENTAL CRYPTOCOCCOSIS.
AB  - Following infection with 10(3) cells of Cryptococcus neoformans, progressive
      multiplication occurred in all tissues for 7 to 28 days. Thereafter, most mice
      gained control of the infection so that 3 to 6 months after inoculation, tissues
      were usually sterile or contained only small numbers of cryptococci. Survivors
      challenged 1 to 4 months after infection with 10(3) cells lived longer than
      controls and had an increased survival rate. Pretreatment with bacterial
      endotoxin also resulted in protection against cryptococcal challenge. Endotoxin
      protected animals showed no ability to limit the infection until circulating
      antibody could be demonstrated. Histologic studies revealed an increased cellular
      infiltration in the brains of specifically protected and endotoxin-protected mice
      1 to 2 weeks after challenge. However, control of cryptococcal multiplication
      could be correlated with the presence of antibody but could not be correlated
      with the enhanced cellular response. Although protection against cryptococcal
      challenge appears to be antibody-dependent, it is unclear whether protective
      antibody is to be found in plasma or is tissue-bound.

PMID- 19867227
TI  - A HEMOLYTIC SYSTEM ASSOCIATED WITH ENTERITIS IN RABBITS : I. NATURE OF THE CELL
      CHANGE AND THE SERUM FACTORS CONCERNED.
AB  - A disease characterized by frequent association of enteritis and polyagglutinable
      cells often develops in weanling rabbits. The red cell lesion renders the cells
      susceptible to agglutination and hemolysis in normal rabbit sera. The degree of
      red cell abnormality varies among different animals and disappears when the
      animals recover. The abnormality of the red cells responsible for their
      polyagglutinability and susceptibility to hemolysis was resistant to the action
      of trypsin or papain and persisted in heated stroma preparations derived from
      polyagglutinable cells. The factors necessary for agglutination and hemolysis of
      the polyagglutinable cells are present in normal rabbit sera but are lacking in
      the sera of affected rabbits. These factors returned to normal levels as the
      polyagglutinable cell lesion disappeared. The sera of rabbits with
      polyagglutinable cells contained normal levels of complement and properdin.
      Whereas the agglutinating factor in normal sera is heat-stable at 56 degrees C
      for 30 minutes, the hemolytic factor is heat labile. The hemolytic factor is
      apparently distinct from complement and properdin since it was adsorbed from
      normal rabbit serum by zymosan or by polyagglutinable cells at 0 degrees C.
      However, complement was fixed when normal rabbit serum was reacted with stroma
      from polyagglutinable cells. Hemolysis of polyagglutinable cells by normal rabbit
      serum at 25 degrees C was inhibited by preliminary incubation of the mixture at 0
      degrees C prior to incubation at 25 degrees C. Evidence was obtained which
      indicated that this inhibition was due to progression of a reaction involving
      Ca(++) independent of a reaction involving Mg(++).

PMID- 19867228
TI  - AN ASSAY OF GRAFT-HOST INTERACTIONS ACROSS STRONG AND WEAK HISTOCOMPATIBILITY
      BARRIERS IN MICE.
AB  - 1. A new assay of graft-host interactions has been presented. It consists of the
      early finding of liver infiltrates in responsive and unresponsive homologous
      recipients 1 to 3 days after the intravenous injection of competent lymphoid
      tissue in the mouse. 2. Evidence is presented that infiltrates are of donor
      origin, and are influenced by a homologous antigenic environment. They can be
      quantitatively increased by preimmunization of donor to recipient and decreased
      by preimmunization of recipient to donor. Furthermore, they are present in
      lethally x-irradiated or neonatally thymectomized unresponsive recipients after
      intravenous injection of competent homologous spleen cells. 3. Splenomegaly,
      which also occurs in this early period, is a product of both donor and host
      specific immune reactivity together with a small non-specific component of host
      reactivity. 4. A comparison, of the responsiveness of lymphoid tissue from
      different strains to the same transplantation antigens is presented, together
      with the observation of differences in the reactivity of reciprocal donor
      recipient injection combinations to each other. 5. Graft-host interactions with
      this model can be demonstrated in donor-host strain combinations isogenic at the
      H-2 locus without preimmunization of the donor. Differences in reactivity of
      reciprocal donor-recipient combinations of lymphoid tissue injections to each
      other can be detected in this group as well as in the groups differing at the
      strong H-2 locus.

PMID- 19867229
TI  - STUDIES ON ANTIBODY PRODUCTION : VI. THE COURSE, SENSITIVITY, AND HISTOLOGY OF
      THE SECONDARY RESPONSE IN VITRO.
AB  - The in vitro anamnestic antibody response of popliteal lymph node fragments to
      additions of antigen closely resembles the in vivo anamnestic antibody response
      in its sensitivity to antigen, in the time course of antibody production, and in
      the sequence of appearance and the morphology of the antibody containing cells.
      Most of the cells responsible for antibody synthesis remain in the explant and do
      not migrate, although a few can be found in the outgrowing sheet of cells. The
      smallest concentration of bovine serum albumin which stimulates an anamnestic
      response in vitro is about 1 x 10(-9) gm/ml.

PMID- 19867230
TI  - STUDIES ON ANTIBODY PRODUCTION : VII. THE EFFECT OF 5-BROMODEOXYURIDINE ON THE IN
      VITRO ANAMNESTIC ANTIBODY RESPONSE.
AB  - Incorporation of 5-bromodeoxyuridine (BUDR) in the culture medium for the 2nd,
      3rd, or 4th day after in vitro antigen stimulation of rabbit popliteal lymph node
      fragments suppressed the in vitro anamnestic antibody response described
      previously. Before or after this 3-day period, BUDR had no measurable effect. The
      results suggest that the antibody response in this in vitro system depends upon
      cell multiplication during this period.

PMID- 19867231
TI  - THE EFFECT OF EXCESS VITAMIN A ON THE EMBRYONIC RAT OESOPHAGUS IN CULTURE.
AB  - The effect of excess vitamin A on the oesophageal epithelium of late foetal rats
      has been studied in organ culture. In explants kept in normal medium the
      epithelium is, at first, higher and the keratinisation increased as compared with
      the development of the organ in vivo. At the later stages of growth, the
      acceleration of keratinisation leads to an extreme thinning of the epithelium.
      Excess vitamin A completely inhibits keratinisation and induces a transformation
      of the cells lining the oesophageal lumen into mucin-secreting elements. In
      vitamin A-treated cultures the epithelium remains high throughout the whole
      period of cultivation. The amount of secretory matter and the height of the
      epithelium seem to depend on an adequate supply of oxygen and carbon dioxide to
      the cells.

PMID- 19867232
TI  - SELECTIVE DESTRUCTION IN TESTIS INDUCED BY 7,12-DIMETHYLBENZ [a] ANTHRACENE.
AB  - After a single feeding or intravenous injection of 7,12
      dimethylbenz[a]anthracene, the testis of rat was severely and selectively
      damaged, whereas the ovary of sisters was spared from injury. After many weeks,
      complete recovery of the testis ensued. The destructive effect of 7,12-DMBA on
      testis was not shared by other powerful carcinogenic hydrocarbons; 3
      methylcholanthrene; benzo[a]pyrene; 2-acetaminophenanthrene. The primary sites of
      destruction inflicted by 7,12-DMBA on testis were spermatogonia and resting
      spermatocytes, the only cells in testis which synthesize deoxyribose nucleic
      acid. No other cells in the germinal epithelium are damaged by 7,12-DMBA. The
      severe atrophy of testis that ensues after some weeks is secondary to destruction
      of precursors in the seminiferous cell line. Moreover, interstitial cells of
      testis are not destroyed by the hydrocarbon. Estimation of malic dehydrogenase is
      a simple and useful quantitative measure of damage and subsequent repair in
      testis. Following administration of 7,12-DMBA, the level of MDH had an inverse
      relationship to weight of the testis.

PMID- 19867233
TI  - INSULIN ANTIBODY VARIATIONS IN RABBITS AND GUINEA PIGS AND MULTIPLE ANTIGENIC
      DETERMINANTS ON INSULIN.
AB  - 1. A method is presented for measuring the degree to which insulin antibodies in
      one antiserum react with an insoluble insulin complex saturated with antibodies
      from a different antiserum. 2. Many rabbits produce antibodies which bind to
      portions of the insulin molecule to which antibodies from guinea pigs or other
      rabbits cannot bind. 3. Occasional guinea pigs produce antibodies which bind to
      portions of the insulin molecule to which antibodies from rabbits or other guinea
      pigs cannot bind. 4. Studies with labeled antisera and repeated incubations of
      test antisera with antibody insulin complexes demonstrate the individual antibody
      variations to be due to antibodies directed to different determinants and not to
      dissociation of antibodies from the same determinant on the insulin molecule. 5.
      More than one antibody molecule can simultaneously bind to an insulin molecule.
      6. Insulin has a multiplicity of antigenic determinants. 7. The relationship
      between antigenic determinants, insulin antibodies, and neutralization of insulin
      by antisera is discussed. 8. The determinants to which insulin antibodies are
      directed appear to be characteristic for the individual rabbit or guinea pig
      immunized. It is postulated therefore that genetic factors direct antibody
      production toward specific determinants when insulin is the antigen.

PMID- 19867234
TI  - EFFECT OF ACTINOMYCIN D ON RNA SYNTHESIS AND ANTIBODY FORMATION IN THE ANAMNESTIC
      RESPONSE IN VITRO.
AB  - Antibody synthesis in anamnestic lymphoid cells, measured by incorporation of
      leucine-C(14) into specific antibody, was inhibited at moderate concentrations of
      actinomycin D. This was accompanied by marked inhibition of synthesis of RNA as
      measured by incorporation of H(3)-cytidine monophosphate. However, at low
      concentrations of actinomycin D, antibody synthesis was unaffected or even
      increased while RNA synthesis continued to be inhibited. The results obtained
      suggest that messenger RNA for antibody synthesis, either because it is
      relatively stable or present in excess, does not become a limiting factor until
      its synthesis is maximally inhibited. Puromycin, an inhibitor of amino acid
      coupling, abolished antibody synthesis in low concentration. 6-Mercaptopurine had
      no effect on the synthesis of antibody or RNA even at high concentration. The
      data obtained support the view that antibody synthesis follows pathways similar
      to those utilized for the formation of other types of proteins.

PMID- 19867235
TI  - THE PATHOGENESIS OF WAXY DEGENERATION OF STRIATED MUSCLES (ZENKER'S
      DEGENERATION).
AB  - In view of theoretical deductions and the positive results obtained in the above
      experiments, it would seem probable that the production of waxy degeneration
      depends upon the action of lactic acid which is formed by the living muscle under
      the stimulation of infecting bacteria or their toxins, the formation of large
      amounts of lactic acid and its accumulation being perhaps favored by defective
      circulation through the injured muscle. The hyaline transformation of muscle
      acted upon by lactic acid is analogous to the swelling of fibrin placed in dilute
      acids. This view is supported by both negative and positive experimental evidence
      the negative evidence being that simple anemic necrosis, aseptic or antiseptic
      autolysis whether in vivo or in vitro, or the action of bacteria of various sorts
      on muscle in vitro, are all incapable of causing changes in muscle cells
      resembling those characteristic of waxy or hyaline degeneration of striated
      muscle. The positive evidence consists in the demonstration that lactic acid,
      even in dilutions comparable to the amounts that can be formed in living muscle,
      can produce a similar or identical waxy transformation of the striated muscle
      fibers, both in vitro and in vivo; and also the observation that muscles
      stimulated to exhaustion, under which condition lactic acid is known to
      accumulate in the muscle, show microscopically changes identical with those of
      Zenker's waxy degeneration.

PMID- 19867236
TI  - THE POSTMORTEM RIGOR OF THE MAMMALIAN HEART AND THE INFLUENCE OF AN ANTEMORTEM
      STIMULATION OF THE PNEUMOGASTRIC NERVES UPON ITS DEVELOPMENT.

PMID- 19867237
TI  - PHAGOCYTIC IMMUNITY.

PMID- 19867238
TI  - ON THE RELATION OF TETANY TO THE PARATHYROID GLANDS AND TO CALCIUM METABOLISM.
AB  - 1. Tetany occurs spontaneously in many forms and may also be produced by the
      destruction of the parathyroid glands. Recent researches tend to demonstrate an
      intimate relation between the various forms of tetany and relative or absolute
      insufficiency of the parathyroid gland. 2. The parathyroid glands are independent
      organs with definite specific function. Whether or not this function is
      intimately related to that of other organs of internal secretion is not as yet
      proven. 3. The number and distribution of the parathyroid glands varies. Failure
      to produce tetany experimentally is probably due to the fact that some
      parathyroid tissue remains after an apparently complete extirpation. When
      extirpation is complete tetany appears, even in herbivora. Only a very small
      amount of parathyroid tissue is required to prevent this. 4. The effect of the
      extirpation of the parathyroid glands may be annulled by the reintroduction of an
      extract of these glands even from an animal of widely different character. The
      active principle is associated with a nucleo-proteid in the extract and may be
      separated with this nucleo-proteid from the remaining inert albuminous
      substances. Its effect in counteracting tetany appears some hours after injection
      and lasts several days. 5. The parathyroid glands contain no considerable amount
      of iodine. The parathyroid extract is not an iodine containing compound. 6. In
      tetany there is apparently some disturbance of the composition of the circulating
      fluids ordinarily prevented by the secretion of the parathyroid, which
      disarranges the balance of the mineral constituents of the tissues. Possibly this
      consists in the appearance of an injurious substance of an acid nature for such
      tetany may he relieved by extensive bleeding with replacement of the blood by
      salt solution. No actual poisonous material has, however, been demonstrated by
      the transference of the blood of a tetanic animal to the veins of a normal one.
      7. Numerous researches have shown the important relation of the calcium salts to
      the excitability of the central nervous system. Their withdrawal leaves the nerve
      cells in a state of hyperexcitability which can be made to disappear by supplying
      them with a solution of a calcium salt. 8. Tetany may be regarded as an
      expression of hyperexcitability of the nerve cells from some such cause. 9. The
      injection of a solution of a salt of calcium into the circulation of an animal in
      tetany promptly checks all the symptoms and restores the animal to an apparently
      normal condition. 10. Injections of magnesium salts probably have a similar
      effect but these effects are masked by the toxic action of the salt. 11. The
      injection of sodium or potassium salts has no such beneficial effect but rather
      tends to intensify the symptoms. This is true also of the alkaline salts of
      sodium which were studied especially in respect to their basic properties. 12.
      The effect of calcium is of value in human therapeutics in combating the symptoms
      of spontaneous forms of tetany and in relieving the symptoms in cases of
      operative tetany and thus tiding over the period of acute parathyroid
      insufficiency until remnants of parathyroid tissue can recover their function or
      new parathyroid tissue can be transplanted. It is in this way an important and
      convenient ally of the method of injecting parathyroid extract. 13. Studies of
      the metabolism in parathyroidectomized animals show: 1. A marked reduction in the
      calcium content of the tissues especially of the blood and brain, during tetany.
      2. An increased output of calcium in the urine and faeces on the development of
      tetany. 3. An increased output of nitrogen in the urine. 4. An increased output
      of ammonia in the urine with 4a. an increased ammonia ratio in the urine. 5. An
      increased amount of ammonia in the blood. Much of this affords evidence of the
      existence of some type of acid intoxication. Its effects are, however, not
      neutralized by the introduction of alkaline sodium salts and may perhaps be
      regarded as especially important in producing a drainage of calcium salts from
      the tissues which can be remedied by the reintroduction of calcium salts. 14.
      Emphasis must be laid upon the remarkable difference which exists between the
      alterations inmetabolism following thyroidectomy and those following
      parathyroidectomy. In myxoedema there is lowered metabolism, decreased
      respiratory changes and lowered nitrogen output with depression of body
      temperature. In tetany there is increased metabolism, probably increased
      respiratory changes, certainly increase in nitrogen output and elevation of the
      temperature. 15. It is important, therefore, that in any experiments upon
      metabolism in relation to the thyroid and parathyroid gland, these glands should
      be clearly distinguished as structures exercising very different and in large
      part contrary effects upon metabolism. 16. In general the role of the calcium
      salts in connection with tetany may be conceived of as follows: These salts have
      a moderating influence upon the nerve cells. The parathyroid secretion in some
      way controls the calcium exchange in the body. It may possibly be that in the
      absence of the parathyroid secretion, substances arise which can combine with
      calcium, abstract it from the tissues and cause its excretion and that the
      parathyroid secretion prevents the appearance of such bodies. The mechanism of
      the parathyroid action is not determined, but the result, the impoverishment of
      the tissues with respect to calcium and the consequent development of
      hyperexcitability of the nerve cells, and tetany is proven. Only the restoration
      of calcium to the tissues can prevent this. 17. This explanation is readily
      applicable to spontaneous forms of tetany in which there is a drain of calcium
      for physiological purposes, or in which some other condition causes a drain of
      calcium. In such cases the parathyroid glands may be relatively insufficient.

PMID- 19867239
TI  - FATAL SEPTICEMIA IN MACACUS RHESUS CAUSED BY A STREPTOCOCCUS DECOLORIZED BY
      GRAM'S METHOD.
AB  - A Gram-negative streptococcus is associated with one form of fatal septicemia
      arising naturally in Macacus rhesus confined in laboratories. This streptococcus
      differs from Streptococcus pyogenes in its behavior to Gram's method of staining;
      in its slight fermentative powers; in the persistence of vitality for a very long
      time in its cultures; in its high degree of pathogenicity for certain lower
      animals; and in the preservation of its virulence undiminished for many months
      when cultivated upon artificial media. In the present state of our knowledge this
      streptococcus must be considered as not identical with any streptococcus
      heretofore described.

PMID- 19867240
TI  - AUTO- AND ISOTRANSPLANTATION, IN DOGS, OF THE PARATHYROID GLANDULES.
AB  - 1. The autotransplantation of parathyroid glandules into the thyroid gland and
      behind the musculus rectus abdominis has been successful in sixty-one per cent.
      of the cases in which a deficiency greater than one-half has been created. 2. In
      no instance has the autotransplantation succeeded without the creation of such
      deficiency. 3. Isotransplantation has been uniformly unsuccessful. 4. Parathyroid
      tissue transplanted in excess of what is urgently required by the organism has
      not lived. 5. One parathyroid autograft may suffice to maintain the animal in
      good health and spirits for many months and possibly for years. 6. Excised or
      deprived of their blood supply in the course of operation upon the human subject,
      parathyroid glands should, in the present state of our knowledge, be grafted, and
      probably into the thyroid gland. 7. Complete excision of the thyroid lobes in
      dogs may be well borne for a year or more. The myxoedema which usually has
      manifested itself within a few weeks has not increased after the first few
      months. May it subsequently diminish with the hypertrophy of accessory thyroids?
      8. Parathyroid tissue is essential to the life of dogs, as has been conclusively
      proved by the result of excision of the sole, sustaining graft. There may be
      found, perhaps, in our experiments, explanation of the fact observed by others
      (Enderlen, Payr) that, when transplanted, thyroid preserves its integrity less
      well than parathyroid tissue. In the instances recorded the amount of thyroid
      gland excised may have been insufficient to make possible the fullest success of
      the transplantation; and particularly so when we consider the extent of the
      hypertrophy of which the thyroid gland seems capable.

PMID- 19867241
TI  - THE CATALYTIC ACTIVITY OF THE BLOOD IN RELATION TO (1) THE FUNCTIONAL SUFFICIENCY
      OF THE KIDNEYS; (2) PERITONITIS.
AB  - 1. The inhibiting action of urine on catalase depends to a great extent on its
      reaction. The urine of a nephritic has no greater inhibiting power than normal
      urine provided the reaction of urines tested is neutral. 2. The catalytic
      activity of a single rabbit's blood is constant from day to day. 3. There is
      considerable variation in the catalytic action of the blood of different rabbits.
      4. Following ligation of the ureters the catalytic activity of the blood
      gradually decreases; the tissues of an animal which has died as a result of
      ligation of the ureters show a decided decrease in catalytic activity, when
      compared with those of normal animals. 5. Following bilateral nephrectomy the
      same decline of the catalytic action of the blood is observed as after bilateral
      ligation of ureters. 6. Following unilateral nephrectomy the catalytic activity
      of the blood may temporarily fall and then rise above its previous level, or it
      may fall continuously. Wherever the continuous fall occurs the animal dies. 7.
      When the kidneys are allowed to function but the urine is drained into the
      peritoneal cavity there is no change in the catalytic activity of the tissues
      post-mortem but a marked rise in the catalytic activity of the blood accompanies
      the resulting peritonitis. 8. The same rise in the catalytic activity of the
      blood is obtained in experimental bacterial peritonitis. This might be of
      diagnostic importance in determining early inflammations of the peritoneum. 9. A
      kidney functioning normally changes substances circulating in the blood into
      urinary products devoid of any influence on catalase. If the kidney cannot effect
      this change, these substances remain unaltered in the circulating blood and by
      their presence inhibit the catalytic activity of the blood and organs. 10.
      Nephritis (Uranium Nitrate).-A. In acute nephritis there is a marked decrease in
      the catalytic activity of the blood and of the tissues post-mortem. The decrease
      in the catalytic activity of the blood may vary directly with the amount of urine
      excreted. B. With the onset of uraemia the catalytic activity of the blood
      decreases markedly and follows in a general way the urinary findings, especially
      the total amount of urine. If the animal recovers the catalase gradually rises.
      C. Although the catalytic activity of a normal rabbit's blood is constant from
      day to day, the activity of blood from a rabbit in which an experimental
      nephritis has been produced oscillates markedly. The catalytic activity of the
      blood may under certain conditions indicate the functional sufficiency of the
      kidneys much more accurately than the urinary findings.

PMID- 19867242
TI  - THE RELATION OF THE WEIGHT OF THE CONTENTS OF STOMACH AND CECUM TO THE BODY
      WEIGHT IN RABBITS.

PMID- 19867243
TI  - THE BORDET-GENGOU BACILLUS OF PERTUSSIS.
AB  - The bacillus of Bordet and Gengou is present in the sputum in early cases of
      pertussis, and in the lungs at autopsy in fatal cases of the disease. After the
      second week it is not present in the sputum in sufficiently large numbers to be
      readily isolated. The influenza bacillus is found at as early a stage of
      pertussis as is the Bordet-Gengou bacillus, and it persists in the sputum for a
      longer time. The agglutinins in the blood of pertussis patients are not more
      regular and not always higher for the Bordet-Gengou bacillus than for B.
      influenzae. The two organisms are culturally distinct and their action on
      laboratory animals different. Complement deviation tests with the serum of
      immunized rabbits show a further difference in the immune bodies produced by the
      two varieties of bacilli. The negative results of the complement deviation tests
      with the patients' serum in this study, compared with the positive results of
      similar tests made by Bordet and Gengou, I am not able to account for. This study
      has contributed support to the view that the Bordet-Gengou bacillus is the
      possible cause of pertussis, but it has not produced any distinctively new
      evidence of this relationship beyond the proof of the wide dissemination of the
      peculiar bacillus in nature and its occurrence in pertussis. A study of bronchial
      secretions in other acute diseases of the respiratory tract for the bacillus has
      not yet been extensively made and is called for. I shall hope to report on this
      phase of the subject at another time.

PMID- 19867244
TI  - THE EFFECT OF CONDITIONS UPON THE LATENT PERIOD AND RATE OF ASEPTIC POST MORTEM
      AUTOLYSIS DURING THE FIRST TEN HOURS.
AB  - 1. Under certain conditions, general autolysis does not begin immediately upon
      the removal of the organ from its circulation. This latent period is more apt to
      be present in those cases in which the tissues have been temporarily cooled on
      account of the use of a cold saline diluent or in which the percentage
      concentration of the inorganic salts (calcium or potassium), of the tissues have
      been changed by dilution with a sodium chloride solution. The presence of blood
      and absence of fats and of glycogen in the cells act as important factors in
      prolonging the latent period. 2. Attempts to produce an alkaline reaction
      (phenolphthalein) in the tissue resulted negatively. Solutions of disodium
      hydrogen phosphate and of sodium bicarbonate when added to the liver tissues gave
      a mixture which was acid to phenolphthalein and had no apparent effect upon
      autolysis. 3. The addition of antiseptics-chloroform and toluol-markedly
      decreased the rate of autolysis. Ordinary light produced no effect. 4. Ethyl
      butyrate when added to the tissue became hydrolysed into butyric acid; the
      formation of this acid in the mixture caused a decided acceleration in the
      autolytic rate. The acidity of a solution of dihydrogen sodium phosphate failed
      to produce a similar result. 5. The figures for the changes in the depression of
      the freezing-point, non-coaguable nitrogen and reaction of the autolytic mixture
      do not parallel one another. In some experiments a marked increase in the
      depression of the freezing-point was unaccompanied by augmentation of non
      coagulable nitrogen. 6. General autolysis is the sum total of proteolytic,
      amylolytic and lipolytic factors. Each of these autolytic factors may proceed
      alone for a time; the rate of one is decidedly influenced by the presence or
      absence of the others. The acid products which are the result of amylolytic
      (lactic acid) and of lipolytic (higher fatty acids) autolysis, exert a pronounced
      augmentative effect upon the commencement and rate of nitrogenous autolysis.

PMID- 19867245
TI  - THE RELATION OF PROTEIN, LIPOIDS AND SALTS TO THE WASSERMANN REACTION.
AB  - 1. The high value in respect to complement-binding exhibited by blood sera from
      syphilitics and spinal fluids from general paralytics is associated with an
      excessively high content of globulin, but there does not exist a direct
      quantitative relation between the two. Cases of secondary syphilis which have
      been under prolonged and proper medication do not exhibit the globulin increase
      and usually fail to give the Wassermann reaction. The active substances entering
      into the Wassermann reaction are precipitable with the globulin and chiefly with
      the euglobulin fraction of the fluids. 2. Temperatures of 70 degrees to 76
      degrees C. destroy the active substances. Exposed to sunlight the active
      substances deteriorate slowly. A photodynamic substance such as eosin, under the
      direct influence of the sun, brings about their complete and rapid destruction.
      This effect does not occur in the dark. The active substances are subject to
      tryptic and peptic digestion and are destroyed by weak acids and alkalies. 3. The
      active substances in the blood sera and spinal fluids cannot be separated from
      them or from the globulin precipitate by alcohol. 4. There are contained in the
      alcoholic extracts of normal and syphilitic blood and organs certain acetone
      soluble lipoids which possess high antigenic values for the Wasserman reaction.
      Cholesterin is inactive and the bile salts less active than the lipoidal bodies.
      5. Sodium cholate is about as active as sodium taurocholate and glycocholate, but
      neurin and cholin are inactive.

PMID- 19867246
TI  - ACTIVE IMMUNITY PRODUCED BY SO CALLED BALANCED OR NEUTRAL MIXTURES OF DIPHTHERIA
      TOXIN AND ANTITOXIN.
AB  - The foregoing and earlier data taken together demonstrate that an active immunity
      lasting several years can be produced in guinea-pigs, by the injection of toxin
      antitoxin mixtures which have no recognizable harmful effect either immediate or
      remote. They also show, what might have been anticipated, that under the same
      conditions mixtures which produce local lesions and which, therefore, contain an
      excess of toxin produce a much higher degree of immunity than the neutral
      mixtures, and that an excess of antitoxin reduces the possibility of producing an
      active immunity, and may extinguish it altogether. There is, therefore, a certain
      definite relation between the components of the mixture and the degree of
      immunity producible. Furthermore, toxin-antitoxin mixtures do not change
      materially within five days at room temperature. They are apparently more
      efficacious at the end of forty-eight hours than immediately after preparation.
      The experiments finally prove that a relatively high degree of active immunity
      can be induced by a harmless procedure, whereas the use of toxin alone leading to
      very severe local lesions is incapable of producing more than an insignificant
      protection. The method, therefore, invites further tests in regard to its
      ultimate applicability to the human being. Unless the subcutis of the guinea-pig
      reacts to toxin-antitoxin mixtures in a manner peculiar to itself, a practical,
      easily controlled method for active immunization can be worked out which should
      afford a larger protection than the serum alone and avoid the complications
      associated with horse serum. That proportion of toxin and antitoxin which would
      produce the highest desirable immunity consistent with the least discomfort would
      have to be carefully worked out for the human subject. From the nature of the
      immunity induced it is obvious, however, that such a method of immunization
      cannot take the place of a large dose of antitoxin in exposed individuals who
      must be protected at once. It would be applicable only as a general protective
      measure without reference to any immediate danger, since it would take several
      weeks, perhaps longer, to perfect the attainable immunity. Passing to the
      theoretical aspects of the facts observed, we find no publications bearing
      directly upon the subject before us. Madsen has, however, approached it very
      closely in his experiments on the immunization of animals with mixtures not fully
      balanced, or, in other words, in which the "toxones" were still free. He found
      that the injection of such mixtures in rabbits, goats and horses produces an
      active immunity. He makes the significant remark that perhaps in the immunizing
      capacity we may possess the keenest reagent for a poison which is not able to
      exert any toxic action in the body. This is fully borne out by the experiments
      described, for in these we pass beyond the visible spectrum, so to speak, of the
      toxin-antitoxin effects, and we are able to recognize toxic action only by the
      lasting immunizing effects. Another publication which touches upon some phases of
      the same problem is that of Morgenroth on the union between toxin and antitoxin.
      Morgenroth brought out the fact that a given toxin-antitoxin mixture is more
      toxic when injected directly into the circulation than when injected under the
      skin. Thus, an L(+) dose of 0.78 c.c. toxin + one unit antitoxin applied
      subcutaneously was of the same toxicity as 0.68 c.c. toxin + one unit antitoxin
      injected into the circulation. When the mixture had stood twenty-four hours this
      (L(+)) dose was still 0.78 c.c. subcutaneously, but it had risen to 0.74 c.c.
      when introduced by the intracardiac route. The author makes two deductions from
      these results. He assumes that the velocity of reaction between toxin and
      antitoxin is slow, and that the union is not completed until the mixture has
      stood twenty-four hours. Hence, the L(+) dose of toxin injected into the blood is
      higher after twenty-four hours than immediately after mixing the toxin and
      antitoxin. He furthermore explains the fact that the subcutaneous L(+) dose
      remains the same whether the mixture is injected at once or after twenty-four
      hours, by assuming that in the subcutis of the guinea-pig there is a catalytic
      acceleration of the union of toxin and antitoxin. In view of the writer's results
      it seems that not only immediately, but four to five days after the preparation
      of the mixture of toxin and antitoxin, there are still toxic substances available
      for the production of immunity in the body of the guinea-pig, when the dose of
      toxin in the mixture is far below the L(0) or neutral level. These toxins may be
      free, either because uncombined in vitro, or else because the mixture is
      partially dissociated in vivo, or there may be a third possibility. It is obvious
      that Morgenroth's investigations, however extensive and thorough, have not
      exhausted the subject, for both these inferences are incompatible with his.
      Perhaps his recent important studies on the recovery of toxin from its
      combination with antitoxin with weak acids may throw more light on this subject.
      The only conclusion which we may safely draw at this time is that the toxin
      antitoxin mixture produces two sets of effects, essentially identical, however.
      One is visible, as injury (oedema, loss of hair, superficial and deep necrosis of
      skin, paralysis and death), and corresponds to the toxin spectrum of Ehrlich. The
      other is invisible and manifests itself only in degrees of active immunity. At
      what ratio of toxin to antitoxin in the mixture active immunity is no longer
      produced will vary somewhat with the guinea-pig used, but it is evident that
      traces of immunity are still transmitted to the young when the amount of toxin
      approaches half the L(0) dose.

PMID- 19867247
TI  - THE HISTOLOGICAL CHANGES IN NERVE CELLS DUE TO TOTAL TEMPORARY ANAEMIA OF THE
      CENTRAL NERVOUS SYSTEM.
AB  - With the return of the circulation, dilation of the pericellular lymph space and
      slight swelling of the cell body occurs, disappearing as recovery progresses.
      Chromatolysis, as evidenced by poor affinity for stains, clumping, diffuse
      staining, and breaking into dust-like particles, induced by anaemia, is not
      necessarily fatal. Death of the cell is not shown histologically when tissue is
      removed and fixed immediately after the experiment. Some time must elapse for the
      detection of the vacuolation, displacement of the nucleus and solution of the
      chromatic substance, indicative of profound changes. Neurones from different
      regions as well as neurones of the same region differ in degree of resistance to
      anaemia. The small pyramidal cells are the most susceptible, and then come the
      Purkinje cells, cells of the medulla oblongata, retina, cervical cord, lumbar
      cord, spinal ganglia and, most resistant of all, the sympathetic ganglion cells.
      Failure to resuscitate animals after anaemia of the central nervous system is
      probably due to the destruction of many of the cells of the vital centers (vaso
      motor and respiratory) which do not have histological peculiarities by which they
      may be defined. Death, however, of a few cells of any center does not necessarily
      mean the total loss of function of that center, since the remaining cells may be
      sufficient to discharge the function of the center.

PMID- 19867248
TI  - A STUDY OF THE PATHOLOGICAL ANATOMY OF THE PANCREAS IN NINETY CASES OF DIABETES
      MELLITUS.
AB  - 1. Anatomical lesions of the pancreas occur in more than seven-eighths of all
      cases of diabetes mellitus. 2. In diabetes associated with lesions of the
      pancreas, the islands of Langerhans constantly show pathological changes
      (sclerosis, hyaline degeneration, infiltration with leucocytes and hypertrophy).
      3. In some cases of pancreatic diabetes (twelve of ninety cases) the lesion of
      the pancreas is limited to the islands of Langerhans. 4. In sixteen cases of
      diabetes associated with hyaline degeneration of the islands of Langerhans the
      average duration of the disease has been three and a half years; in forty-six
      cases with sclerosis of these bodies, three years and eleven months. In six cases
      of diabetes associated with an infiltration of leucocytes about the islands of
      Langerhans the average duration has been eleven months. 5. Destructive lesions of
      the islands of Langerhans may be associated with compensatory hypertrophy of
      other interacinar islands. 6. Peculiar adenoma-like hypertrophy of the islands of
      Langerhans occurs in a small proportion of cases (seven of ninety) and may be
      associated with adenomata of the thyroid gland (two cases) and of the pituitary
      body (one case). 7. Diabetes mellitus occurring in association with
      haemochromatosis (bronzed diabetes) is referable to pigmentation and destruction
      of the islands of Langerhans. 8. The pancreas is found to exhibit no pathological
      changes in twelve per cent. of cases. In approximately one-half of these cases it
      has been noted that the size of the gland or the number of islands is much less
      than normal. 9. Fifty per cent. of cases of diabetes mellitus occurring before
      the age of thirty years are associated with lesions of the pancreas; seventy-five
      per cent. of all cases of diabetes in which the pancreas is normal occur before
      the age of thirty years. Ninety-seven per cent. of cases of diabetes occurring
      after the age of thirty years are associated with lesions of the pancreas; and
      eighty-six per cent. occur in association with chronic interacinar pancreatitis
      accompanying arteriosclerosis. 10. Interacinar pancreatitis which occurs in
      seventy-three per cent. of all cases of diabetes is almost constantly associated
      with arteriosclerosis: gangrene of the extremities, which occurs with one-fourth
      of all cases of interacinar pancreatitis, is doubtless referable to the same
      cause. 11. Chronic interlobular pancreatitis, when associated with diabetes, is
      accompanied by sclerosis or hyaline degeneration of the islands of Langerhans.
      12. Diabetes in association with myxoedema or with exophthalmic goiter may be
      referable to a lesion of the pancreas, namely, chronic interacinar inflammation
      with sclerosis of the islands of Langerhans; diabetes in association with
      acromegaly may be referable to a lesion of the islands of Langerhans, namely,
      sclerosis and hyaline degeneration with adenoma-like hypertrophy.

PMID- 19867249
TI  - STUDIES IN EDEMA : I. COMPARATIVE INVESTIGATION INTO THE ACTION OF CALCIUM
      CHLORIDE AND SODIUM CHLORIDE ON THE PRODUCTION OF URINE, INTESTINAL FLUID AND
      ASCITES.
AB  - 1. The secretion of urine and the elimination of fluid through the intestinal
      canal which are caused by the intravenous injection of solution of 0.85 per cent.
      sodium chloride are decreased by the addition of calcium chloride to the sodium
      chloride solution. The secretion of urine is more markedly inhibited than is the
      elimination of fluid through the intestines. 2. In contradistinction to the
      decreased elimination of fluid through the kidneys and intestines, addition of
      calcium chloride to the sodium chloride solution increases markedly the
      transudation of fluid into the peritoneal cavity. To a certain degree the urine
      and ascites may be said to increase in an inverse proportion. 3. Although calcium
      chloride inhibits both absorption from and secretion into the intestines it seems
      to decrease the secretion more markedly than the absorption. 4. The action of
      calcium chloride in increasing the ascitic fluid is a double one: first, by
      diminishing the amount of urine secreted: secondly, by increasing the ascites
      independently of its action on the kidneys. The latter may be a direct action on
      the endothelial cells of the peritoneal cavity: this, however, must be determined
      by further investigations. 5. Addition of calcium chloride to the infused fluids
      increases the tendency to the occurrence of edema of the lungs. 6. Infusion of
      large quantities of fluid into animals dilutes the blood, but this dilution seems
      to be carried only to a certain degree- about 30 per cent.-and to be independent
      of the chemical character of the solution and of the function of the kidneys. 7.
      The presence or absence of the kidneys has a marked influence on the intestinal
      and ascitic fluids. When the averages of ascitic and intestinal fluids per 1,000
      c.c. of retained fluid in non-nephrectomized animals and these fluids per 1,000
      c.c. of infused fluid in nephrectomized animals are compared, more fluid is found
      in the case of the nephrectomized animals. This fact can only be explained in
      part by the shorter time necessary for the same amount of fluid to be retained in
      the case of the nephrectomized animals. Nephrectomy causes an increase of the
      ascites and the intestinal fluids through a mechanism which will have to be
      investigated by means of further experiments.

PMID- 19867250
TI  - THE POSTMORTEM RIGOR OF THE MAMMALIAN HEART AND THE INFLUENCE OF AN ANTEMORTEM
      STIMULATION OF THE PNEUMOGASTRIC NERVES UPON ITS DEVELOPMENT.
AB  - IN NORMAL ANIMALS (DOGS, CATS AND RABBITS) WHICH WERE KILLED BY EXSANGUINATION,
      THE BEGINNING OF RIGOR IN PRACTICALLY ALL CASES WAS SEPARATED FROM RESPIRATORY
      DEATH BY TWO WELL CHARACTERIZED PERIODS: (1) a period of pulsation during which
      each ventricle still exhibited some spontaneous contractions, and (2) a period of
      relaxation during which the ventricles, while showing neither spontaneous
      contractions nor rigor, are more relaxed than in normal diastole, and during
      which the ventricles gradually lose their irritability. (The cardiac rigor or
      tonic contraction which was observed by recent investigators to set in
      immediately after death is an artificial phenomenon produced by filling the heart
      with saline and connecting it with a manometer.) In the right ventricle both
      periods are longer than in the left ventricle, i. e., rigor sets in later.
      Moreover the development of rigor from onset to maximum is also longer in the
      right ventricle than in the left, although here the difference is less striking.
      The stopping of spontaneous beating, the disappearance of irritability, and the
      development of rigor, manifest in both ventricles a topographical progress from
      the base toward the apex, i. e., the stoppage of beating, the disappearance of
      irritability and the setting in of rigor occur first at the uppermost part of the
      ventricle and last at the lowest point of the ventricle. It often occurred that
      rigor was already present in the basal part of a ventricle while the apex was
      still beating. It is probable also that the loss of vital activity and
      irritability and the development of rigor progress topographically from the
      endocardial to the epicardial surfaces. Prolonged etherization retards the onset,
      but hastens the development of rigor; atropinization hastens both onset and
      development. Repeated prolonged stoppages of the heart caused by antemortem (and
      postmortem) stimulations of the pneumogastric nerves hasten the onset as well as
      the development of rigor of the heart. All three periods are affected by the
      inhibitory influence of the stimulation, the period of relaxation, however, seems
      to be the one which is shortened most. The most probable interpretation of this
      phenomenon is the assumption that it is caused by an asphyxiation of the cardiac
      tissues. The stimulations of the pneumogastric nerves seem to hasten also the
      onset of the general rigor-probably this, too, is the result of some premature
      asphyxiation of the skeletal muscles.

PMID- 19867251
TI  - THE ACTION OF GLANDULAR EXTRACTS UPON THE CONTRACTIONS OF THE UTERUS.

PMID- 19867252
TI  - THE PRESENCE OF A WEAK HEMOLYSIN IN THE HOOK WORM AND ITS RELATION TO THE ANEMIA
      OF UNCINARIASIS.
AB  - 1. The hook worm of man-both the Old and New World types-contains a weak
      hemolytic agent active in vitro. It is soluble in salt solution, is easily
      destroyed by heat and acts slowly. 2. The hemolysin is present in all parts of
      the worm and probably is associated with the intestinal tract. 3. The hook worm
      of the dog contains a similar hemolysin. 4. These hemolysins are not specific,
      but will act on human blood as well as on that of the dog and rat. They are only
      demonstrable in concentrated extracts. 5. Concentrated extracts of the human whip
      worm may be hemolytic to some bloods. 6. The round worm of man contains no
      hemolytic principle in any part of its body. 7. It seems very unlikely that this
      weak hemolysin found in the hook worm can have any relation to the anemia of
      uncinariasis. 8. Study of the "blood cysts" in the human intestine shows that the
      hook worm may live in a small amount of the host's blood for days without causing
      any marked hemolysis.

PMID- 19867253
TI  - AN EXPERIMENTAL STUDY OF THE METABOLISM AND PATHOLOGY OF DELAYED CHLOROFORM
      POISONING.

PMID- 19867254
TI  - PARTIAL, PROGRESSIVE AND COMPLETE OCCLUSION OF THE AORTA AND OTHER LARGE ARTERIES
      IN THE DOG BY MEANS OF THE METAL BAND.

PMID- 19867255
TI  - A NEW AND SIMPLE METHOD FOR THE SERUM DIAGNOSIS OF SYPHILIS.

PMID- 19867256
TI  - STUDIES IN ATYPICAL FORMS OF TUBERCLE BACILLI ISOLATED DIRECTLY FROM THE HUMAN
      TISSUES IN CASES OF PRIMARY CERVICAL ADENITIS : WITH SPECIAL REFERENCE TO THE
      THEOBALD SMITH GLYCERINE BOUILLON REACTION.
AB  - The four cultures which form the basis of this communication were recovered from
      peculiar cases of primary cervical adenitis in man, three of which terminated
      fatally of disseminated acute miliary tuberculosis in four to six weeks. A
      careful comparative study shows that Culture II corresponds closely with the
      "human" and Culture IV with the "bovine" type of tubercle bacilli; while Cultures
      I and III present variations from the standard types and are to be retarded as
      "intermediate" or "atypical" forms. Culture I is of unusual interest because of
      its remarkable variations. The clinical picture of the case, the rapid course of
      the infection, the enormous number of the bacilli in the tissue, their tendency
      to occur in "heaps" like the leprosy bacillus, the high degree of virulence alike
      for rabbits and guinea-pigs, the production of lesions in chickens, the case of
      cultivation and the prolonged viability under unfavorable conditions, all mark
      the organism as a decided atypical form of tubercle bacillus in man. The
      prolonged viability, the production of lesions in the chicken and the great
      profusion of bacillary growth in the tissues would indicate an avian type. Though
      for years the reaction curve was atypical it has since changed completely to the
      "avian" curve. In this connection it is of interest to note that L. Rabinowitsch
      (3) states that she has isolated avian tubercle bacilli from two cases of
      tuberculosis in man. Cultures II and III undoubtedly belong to the human type of
      the tubercle family though they were under cultivation and were repeatedly tested
      upon glycerine broth over a period of months before their identity was definitely
      established. Culture IV completely corresponds in growth and reaction in
      glycerine bouillon to the bovine strain; however, it manifests a low degree of
      virulence for rabbits which is exceptional for bovine cultures. The old belief
      that bovine bacilli are more slender and beaded in the tissues and are thicker
      and shorter in culture than the human type, I have not been able to confirm. The
      morphological characters of the different cultures here reported were so
      inconstant that no reliance could be placed on this feature as an aid in
      differentiation. Outside of the animal body it would seem that the differences in
      size and character of the individual bacilli depend largely on the kind and
      reaction of the medium, whilst in the animal body they are influenced by their
      situation and the resistance of the host. The nature of the growth of these
      tubercle cultures varies for the same culture even under apparently identical
      conditions. The character of the growth was never an indication of the type of
      the culture, It was common to obtain two distinct types of growth on the same
      flask of bouillon, i. e., a portion of the surface would be covered with a heavy
      and uniformly granular layer of closely packed wax-like colonies twice the size
      of an ordinary pin's head, while the other portion would be a dense homogeneous
      layer with the typical depressed blisters. The rapidity of growth also varied
      greatly for the same culture. Often in a series of twelve or more bouillon flasks
      which were prepared alike and inoculated with the same culture, some would cover
      the surface in eight days to two weeks, others would take four to six weeks,
      still others two to three months. It was thought in the beginning of the work
      that this variation might depend on the amount of oxygen within the flask or on
      the change in reaction in the bouillon, but further tests proved that neither of
      these influenced the rate of growth in any way. It would occur in loosely corked
      flasks as well as in those that were sealed, and in flasks where the reaction was
      neutral, acid or slightly alkaline. It would seem that these changes are by no
      means specific for any group of the tubercle bacilli but a property possessed by
      them all. The growth of the cultures on solid medium showed approximately the
      same variation as that from the surface of the glycerine bouillon. The wax-like
      colonies described by L. Rabinowitsch (3) as characteristic for avian tubercle
      bacilli were noted at times for all of the cultures. On the modified egg mixture
      the growth was always more rapid and profuse than on any other medium. I found
      this egg medium more certain than any other for the direct recovery of the
      tubercle bacillus from the tissues. Where it was desired to recover the culture
      from the animal tissues with certainty and celerity it had no equal. Occasionally
      in seven days after the inoculation of the tuberculous gland material the growth
      was sufficiently advanced to transplant to the bouillon flasks. The glycerine
      bouillon test serves admirably to distinguish between the human, bovine and avian
      types of tubercle bacilli. It is also of value in the determination of degrees of
      adaptation in man for bacilli of the lower host-species, and in the recognition
      of "intermediate" types. The test to be of differential value requires repeated
      application and careful control over a period of months. Some freshly isolated
      cultures may produce their specific reaction curve in glycerine bouillon within a
      few weeks. On the other hand the same culture may fail to give its characteristic
      reaction or any alteration in the glycerine bouillon for several months though
      the growth has been luxuriant and complete. The rise in acidity that occurs in
      glycerine bouillon for the human type of tubercle bacilli is due to a specific
      action on the glycerine of the products of disintegration of bacilli (autolysis);
      with the bovine and avian types the products of bacillary disintegration have no
      action on the glycerine. The fall in acidity which occurs for all three types of
      the tubercle bacillus is due to the products of metabolic activity.

PMID- 19867257
TI  - AN EXPERIMENTAL STUDY OF THE INFLUENCE OF KIDNEY EXTRACTS AND OF THE SERUM OF
      ANIMALS WITH RENAL LESIONS UPON THE BLOOD PRESSURE.
AB  - 1. Extracts of the rabbit's kidney injected into the rabbit cause a slight,
      increase in blood pressure which is barely more than that due to the mechanical
      effect of the injection. 2. Extracts of the dog's kidney injected into the dog
      cause a decided fall in pressure; an equal fall may be caused by the dog's urine.
      A series of control experiments indicates that the fall caused by the kidney
      extract may be due to the urinary salts which it contains. 3. Extracts of cat's
      kidney cause a rise in pressure. As the cat's urine causes a fall, this rise in
      pressure indicates the possibility of a kidney extract containing a pressor
      substance which cannot be influenced by the depressor substance of the urine. 4.
      Rabbit's kidney, which in the rabbit produces a slight rise, when injected into
      the dog causes a drop comparable to that caused by the dog's kidney itself.
      Similarly, the dog's kidney, which injected into the dog causes a drop, produces
      in the rabbit a rise analogous to that produced by rabbit's kidney. It is evident
      therefore that these pressor and depressor substances of the kidneys in question
      do not have a constant effect on all animals as do the extracts of the adrenal
      gland. 5. Extracts of kidneys which are the seat of various forms of nephritis
      cause the same effect as extracts of normal kidneys. 6. The serum of dogs with
      considerable reduction of kidney substance causes a slight fall in pressure; the
      serum of dogs with spontaneous nephritis gives divergent results, as does also
      the serum of rabbits with various forms of acute nephritis. The serum of dogs
      with chromate nephritis causes a slight rise, while that of dogs with uranium
      nephritis produces a sharp and decided fall in pressure. Although there is no
      uniformity in these results, their general character, and especially the
      experience with uranium and chromate sera of the dog, suggests that pressure
      disturbing substances are present in the serum as the result of the kidney
      lesion. The very slight evidence of the constant presence of a pressor substance,
      however, offers little support to the theory that such a substance is furnished
      by the diseased kidney or is due to disturbances of metabolism caused by disease
      of the kidney.

PMID- 19867258
TI  - PNEUMOTHORAX AND POSTURE.
AB  - THE LAST MENTIONED FACT MAY PERHAPS FIND ITS EXPLANATION IN THE FOLLOWING
      STATEMENTS: the two pleural cavities are separated by the layers of the anterior
      and posterior mediastinal septa. Between the two lies the heart. In the dog, the
      posterior seems to be somewhat tougher than the anterior septum, and somewhat
      more fixed and tense. With violent respiratory movements, it is the anterior
      septum which more especially flaps to and fro and bulges when an opening in the
      pleura has been made, and it is the anterior septum which is so apt to rupture
      and thus cause double pneumothorax and the death of the animal. When the dog is
      on its back, the heart falls backward and the bulging of the anterior mediastinal
      septum is made more easy. It is different when the animal is on its belly. The
      heart falls toward the anterior chest wall and thus supports the anterior septum:
      hence the flapping of the septum, the interference with the respiration of the
      lung on the sound side, the bulging on expiration on the open side, can not so
      readily occur. The danger of the open pneumothorax is greatly lessened when the
      animal is in the prone position. In the supine position the danger of the
      pneumothorax is due to the falling back of the heart and thus facilitating the
      rupture of the fragile anterior mediastinal septum; the danger is therefore
      obviated by fixing the pericardium to the anterior wall of the thorax.

PMID- 19867259
TI  - THE EFFECTS OF ROENTGEN IRRADIATION UPON THE CHANGES IN THE CELL CONTENT OF THE
      BLOOD AND LYMPH INDUCED BY INJECTIONS OF PILOCARPINE.

PMID- 19867260
TI  - STUDIES IN EDEMA : II. THE INFLUENCE OF THE ADDITION OF ADRENALIN TO SOLUTIONS OF
      SODIUM CHLORIDE AND OF SODIUM CHLORIDE AND CALCIUM CHLORIDE SOLUTIONS AND OF A
      MORE RAPID RATE OF INFLOW UPON THE PRODUCTION OF URINE, ASCITES AND INTESTINAL
      FLUID.
AB  - 1. In non-nephrectomized animals the addition of adrenalin to sodium chloride
      solutions or to mixtures of sodium chloride and calcium chloride solutions
      increases the amount of urine and of ascites, and diminishes the intestinal fluid
      (this diminution takes place only with mixtures of solutions of sodium chloride
      and calcium chloride, the quantity of intestinal fluid remaining approximately
      unchanged in the sodium chloride series). 2. In nephrectomized animals the
      addition of adrenalin to sodium chloride solutions or to mixtures of sodium
      chloride and calcium chloride solutions again increases the ascites and
      diminishes the amount of intestinal fluid in both sodium chloride and sodium
      chloride plus calcium chloride series. 3. We find, therefore, a summation of the
      action of calcium chloride and adrenalin in regard to their influence upon the
      formation of ascites, an antagonistic action in regard to the elimination of
      urine; here the influence of calcium chloride in diminishing the urine is more
      potent than is the action of adrenalin in increasing the amount of urine. The
      adrenalin decreases the elimination of fluid into the intestines and in this case
      we note a summation of the actions of calcium chloride and of adrenalin. 4. We
      see, therefore, that adrenalin and calcium chloride influence the amount of
      ascitic fluid and of intestinal fluid in the same direction. The amount of urine
      is, however, decreased by calcium chloride and increased by adrenalin. 5. If we
      increase the rapidity of inflow of the solutions and simultaneously decrease
      proportionately the time of the infusion, the amount of ascites and intestinal
      fluids in nephrectomized animals remains approximately unchanged, as compared
      with the amounts obtained at the usual rate of inflow.

PMID- 19867261
TI  - STUDIES IN EDEMA : III. THE INFLUENCE OF MYOCARDITIC LESIONS ON THE PRODUCTION OF
      ASCITES, INTESTINAL FLUID AND URINE IN ANIMALS INFUSED WITH SOLUTIONS OF SODIUM
      CHLORIDE AND OF SODIUM CHLORIDE AND CALCIUM CHLORIDE.
AB  - 1. Animals in which experimental myocarditis has been produced and winch are
      infused with sodium chloride solutions show a marked decrease in the amount of
      the secretion of urine. This decrease is even more pronounced than that produced
      when calcium chloride is added to sodium chloride solution. The intestinal fluid
      which is markedly decreased, and the peritoneal transudate which is increased by
      calcium chloride are, on the other hand, not markedly influenced by myocarditic
      lesions. We may, therefore, conclude that calcium chloride does not exert its
      specific effect on the quantity of peritoneal fluid through a lowering of blood
      pressure. 2. Each of the three factors, namely, calcium chloride, adrenalin and
      myocarditic lesions affects the elimination of fluid through the kidneys, through
      the mucosa of the small intestine and through the endothelial lining of the
      peritoneal cavity in a specific way. The conditions influencing the elimination
      of fluids through these three surfaces seem, therefore, to be different in each
      case and characteristic for the cells lining these surfaces.

PMID- 19867262
TI  - STUDIES ON INTRACRANIAL PRESSURE.
AB  - 1. The results of this work form a confirmation of the earlier work of Cushing in
      all details investigated. 2. The increase of blood pressure that results from an
      increase of the intracranial pressure above the blood pressure is due in the dog
      to a vaso-constriction of the vessels of the intestine, the kidney and the limbs.
      Preceding this constriction there is dilatation. 3. The anastomotic connection
      between the internal carotid artery within the skull and the ophthalmic branch of
      the internal maxillary is of a size in the dog approximately equal to the
      internal carotid outside of the skull. The anatomical relations are such as to
      indicate that the internal maxillary artery in this animal is a cerebral artery
      equal in importance to the internal carotid. The anastomotic connection because
      of its position within the cranial cavity is unaffected except by extreme grades
      of intracranial compression. 4. The ordinary method of artificial perfusion of
      the dog's brain as used in physiological investigation appears from this work to
      be of no value, since there is at least one important path open besides that
      through the vessels of the brain. 5. The increase of the intracranial pressure
      above the blood pressure leads to a complete anaemia, superficial and deep, of
      the blood vessels of the brain. If the intracranial pressure is not greatly
      increased above the blood pressure, the circle of Willis and some of the larger
      arterial connections at the base of the brain are more or less well injected. An
      intracranial pressure somewhat below blood pressure leads apparently to a certain
      degree of anaemia directly beneath the point of entrance of the intracranial
      fluid; the condition of the rest of the brain as regards blood supply is normal.

PMID- 19867263
TI  - THE MORPHOLOGY OF THE PARASITE (HISTOPLASMA CAPSULATUM) AND THE LESIONS OF
      HISTOPLASMOSIS, A FATAL DISEASE OF TROPICAL AMERICA.
AB  - Histoplasmosis is a fatal infectious disease of tropical America resembling kala
      azar of India. It is characterized clinically by splenomegaly, emaciation,
      irregular pyrexia, leucopenia and anemia. The pathological features are the
      invasion of endothelial cells in the smaller lymph and blood vessels and
      capillaries by enormous numbers of a small encapsulated microorganism
      (Histoplasma capsulatum) causing necroses of the liver with cirrhosis,
      splenomegaly, psudo-granulomata of the lungs, small and large intestines, with
      ulceration of the latter, and necrosis of lymph nodes draining the injected
      viscera. The disease is caused by a small round or oval microorganism 1 to 4
      micro in diameter possessing a polymorphous, chromatin nucleus, basophilic
      cytoplasm and achromatic spaces all enclosed within an achromatic refractile
      capsule. The microorganism differs from the Leishman-Donovan body of kala-azar in
      the form and arrangement of its chromatin nucleus, and in not possessing a
      chromatin rod.

PMID- 19867264
TI  - AN EXPERIMENTAL GLOMERULAR LESION CAUSED BY VENOM (CROTALUS ADAMANTEUS).
AB  - The venom of Crotalus adamanteus when administered intravenously to rabbits in
      properly graded doses causes lesions of the glomerulus of tile kidney which may
      be either hemorrhagic or exudative in character. Both types of lesion are usually
      associated but either one or the other may predominate. The hemorrhagic lesion,
      which may be confined to the glomerular tuft, or, by rupture of the latter, may
      involve the capsular space, is a peculiar localization of the hemorrhage so
      common in other parts of the body in venom intoxication. On the other hand, the
      exquisite exudative lesion involving usually the capsular space but sometimes
      limited, as in the hemorrhagic type, to the tuft itself and with little or no
      tubular injury, constitutes a type of experimental vascular nephritis, hitherto
      undescribed, which differs widely in its anatomical appearance from that due to
      arsenic, cantharidin and other vascular poisons. As the limitation of the lesion
      to the glomerulus indicates a selective action of the venom, and as the
      histological changes in the tuft are suggestive of gradual endothelial
      destruction and solution, the lesion can be explained by the action of the
      endotheliolytic body of crotalus venom described by Flexner and Noguchi.

PMID- 19867265
TI  - BLOOD-PLATELET AND MEGALOKARYOCYTE REACTIONS IN THE RABBIT.

PMID- 19867266
TI  - EXPERIMENTAL LIPEMIA IN RABBITS.
AB  - In reviewing the literature, no description of a lipemia occurring in relation to
      simple hemorrhage was found, so that the observation of the phenomenon here
      recorded would seem to be new. Very high percentages of fat have been found in
      the blood of diabetics. Fischer's case showed 18.1 per cent total ether extract.
      Of this very little was free fat (0.0018 gm. potassium hydroxide per gram of
      fat); iodine absorption was 60.6 per cent.; cholesterin, 2.6 per cent. Chatin's
      case, cited by Fischer, showed 1.2 per cent. cholesterin, 66.5 per cent. olein,
      32.2 per cent. margarin in the fat. Neisser and Derlin in the ether extract of
      blood from a patient with diabetic coma found 19.7 per cent. fat, with melting
      point of from 39 degrees to 41 degrees C.; iodine absorption was 53.6 per cent.
      Javal in a similar case found 25.4 per cent. of fat in ether extract of dry serum
      (perhaps by Soxhlet method); 21 per cent. of the fat was lecithin. Bleibtreu
      produced alimentary lipemia in geese by feeding barley and butter. Ether extract
      of serum showed 6 per cent. of fat. The serum was milky with invisible droplets.
      Iodine absorption was 57 to 58 per cent. The fat was quite different, chemically,
      from the fat in the food. Lipemia disappeared a few days after discontinuing the
      forced feeding. Our experiments suggest, by analogy, the possible occurrence of
      lipemia in human anemias. In this connection it is of interest to note that we
      have recently demonstrated a moderate lipemia in a case of marked secondary
      anemia from hemorrhoids. The emaciation in such cases, as contrasted with the
      well-recognized conservation of the fat in pernicious anemia, suggests in human
      pathology a still further analogy which we now have under investigation. The fat
      in our lipemic rabbits differs from fats described above in its insolubility, as
      well as in its "constants." The change after precipitation of calcium from the
      serum suggests that the fat may be present in the serum as a protein-calcium
      lecithin combination which is decomposed by decalcifying. While we are not
      prepared to offer an explanation of the mechanism of this lipemia, it is possible
      that the great loss of tissue proteins may have some influence on the abnormal
      fat metabolism. That the fat is derived from the tissues is a fair inference when
      its occurrence in connection with the loss of weight and the previous
      disappearance of the body fat are taken into consideration. A more careful study
      of the lipase in the blood and tissues is desirable. It may be that lowered
      oxidation following great loss of red cells plays a part.

PMID- 19867267
TI  - DATA CONCERNING THE ETIOLOGY AND PATHOLOGY OF HEMORRHAGIC NECROSIS OF THE
      PANCREAS (ACUTE HEMORRHAGIC PANCREATITIS).

PMID- 19867268
TI  - A COMPARATIVE STUDY OF THE DIPLOCOCCI OCCURRING IN EPIDEMIC CEREBRO-SPINAL
      MENINGITIS AND POSTERIOR BASIC MENINGITIS.
AB  - The study carried out and recorded in this paper did not lead to the finding of
      any reliable criteria of difference between strains of Diplococcus
      intracellularis obtained from typical cases of epidemic meningitis and several
      cultures obtained from cases of posterior basic meningitis. The successful
      experiments made with monkeys show that the diplococcus obtained from cases of
      posterior basic meningitis is capable of setting up rapidly and acutely fatal
      forms of meningitis and in producing organic lesions of the cerebral tissues of
      great severity. This study would, therefore, suggest that the antimeningitis
      serum should be as useful in cases of posterior basic meningitis so-called, as it
      has been in epidemic meningitis, especially if it were employed early in the
      disease.

PMID- 19867269
TI  - THE INFLUENCE OF TEMPERATURE ON HEMOLYSIS IN HYPOTONIC SOLUTIONS.
AB  - Decreasing the temperature from 37 degrees C. to 5 degrees C. perceptibly and
      regularly increases hemolysis in hypotonic sodium chloride and cane sugar
      solutions, when the erythrocytes of a number of the common mammals are
      considered. The measurements were carried out with Smith's modification of the
      method of Hamburger. If following the original method of Hamburger one relies on
      the point of beginning hemolysis as an index of corpuscle resistance, the facts
      are not brought out clearly. The effect is in the opposite direction from that
      which would prevail if the laws governing change of osmotic pressure with change
      of temperature were the influential factors. The results possibly depend on some
      change in the permeability or consistence of the erythrocytic protoplasm
      considered as a semi-permeable membrane.

PMID- 19867270
TI  - THE BUTYRIC ACID TEST FOR SYPHILIS IN THE DIAGNOSIS OF METASYPHILITIC AND OTHER
      NERVOUS DISORDERS.
AB  - 1. In the secondary and tertiary stages of syphilis without direct involvement of
      the nervous system the cerebro-spinal fluid yielded the butyric acid reaction of
      feeble intensity. The fluid under these conditions gave neither a positive
      cytodiagnosis nor the Wassermann test for syphilis. 2. The cerebro-spinal fluid
      of cases of hereditary syphilis showed a positive butyric reaction in about 90
      per cent. and a positive Wassermann test in about 80 per cent. of the cases
      examined. 3. The cerebro-spinal fluid of cases of cerebral and spinal syphilis
      yielded the butyric acid reaction and the cytodiagnosis in every instance (100
      per cent.) and gave the Wassermann reaction in from 50 to 75 per cent. of those
      examined. 4. The cerebro-spinal fluid from cases of general paralysis gave
      positive butyric acid reactions in 90 per cent., positive cell counts in 91 per
      cent., and positive Wassermann test in 73 per cent. of those examined. 5. The
      cerebro-spinal fluid from cases of tabes dorsalis gave positive butyric acid
      reactions and cell counts in 100 per cent. and positive Wassermann test in 53 per
      cent. of those examined. 6. The cerebro-spinal fluid from other forms of
      psychosis in which a syphilitic history was not obtained gave positive butyric
      acid reactions and cell count in 2.8 per cent. and Wassermann test in 13 per
      cent. of those examined. 7. The cerebro-spinal fluid from cases of acute
      inflammatory diseases of the meninges always gave a flocculent precipitate with
      the butyric acid reaction but never gave the Wassermann test. 8. The cerebro
      spinal fluid from persons suffering from typhoid fever, pneumonia, pulmonary
      tuberculosis, etc., in which the meninges are not inflamed, gave neither the
      butyric acid nor the Wassermann test. 9. We think it justifiable to conclude that
      the butyric acid reaction affords a ready means of distinguishing normal from
      pathological cerebro-spinal fluid and will prove to be useful in routine clinical
      practice, especially in detecting syphilitic disease and in confirming or setting
      aside certain doubtful diagnoses of syphilitic or metasyphilitic lesions of the
      central nervous system. The reaction should commend itself as a valuable addition
      to the Wassermann test, the results of which it is capable of confirming and
      extending.

PMID- 19867271
TI  - STANDARDIZATION OF THE ANTIMENINGITIS SERUM.
AB  - The high variability in infectivity of Diplococcus intracellularis makes it
      impracticable to standardize the antimeningitis serum on the basis of the
      virulence of the diplococcus. The irregularity of reaction of small animals to
      the poison or endotoxin of Diplococcus intracellularis makes it impracticable to
      standardize the antimeningitis serum on the basis of endotoxic value. The want of
      uniformity in the complement-binding power of the antimeningitis serum, and the
      absence of established relation between complement-binding power and therapeutic
      activity make the employment of this method of standardization impracticable. The
      part taken by specific opsonins in promoting recovery from infection with
      Diplococcus intracellularis suggests their employment as a measure of the
      therapeutic activity of the antiserum. Methods of quantitative estimation of
      opsonic content of the antimeningitis serum being available, it would seem
      advantageous to adopt for the present as a standard of value a definite and
      suitable strength in opsonins of the antimeningitis serum. As a definite and
      suitable standard of strength a minimum dilution activity of a 1 to 5,000
      dilution of the antiserum is proposed. Since the immune opsonins of the
      antimeningitis serum appear to be highly durable under proper conditions of
      refrigeration of the antiserum, the test proposed will be applicable when the
      antimeningitis serum shall have become an article of commerce.

PMID- 19867272
TI  - CONTINUOUS RESPIRATION WITHOUT RESPIRATORY MOVEMENTS.

PMID- 19867273
TI  - STUDIES IN EDEMA : IV. THE INFLUENCE OF CALCIUM CHLORIDE, ADRENALIN, MYOCARDITIS
      AND NEPHRECTOMY UPON THE DILUTION OF BLOOD DURING INTRAVENOUS INJECTION OF SODIUM
      CHLORIDE SOLUTION.
AB  - 1. As a result of the intravenous infusion of a solution of sodium chloride a
      characteristic curve indicating the fluid retained in the vascular system is
      obtained. In the first period of the infusion the maximum of retention of fluid
      is noted. Then more fluid is removed from the blood vessels, so that for a short
      time a fall in the curve of dilution takes place, after which the dilution again
      slowly increases. 2. This curve is not materially changed by the addition of
      calcium chloride or of adrenalin to the infused solution, and under such
      conditions adrenalin does not lead to an increased pressing out of fluid from the
      vascular system, although is causes a constant and decided rise in blood
      pressure. Myocarditic lesions lead to an increased intravascular retention of
      fluid. Nephrectomy does not lead to an increased intravascular retention of
      fluid, but probably causes a diminution of the amount of fluid retained in the
      blood vessels.

PMID- 19867274
TI  - STUDIES IN EDEMA : V. THE EFFECT OF CALCIUM CHLORIDE, ADRENALIN AND MYOCARDITIC
      LESIONS UPON THE BLOOD PRESSURE IN ANIMALS INJECTED INTRAVENOUSLY WITH SODIUM
      CHLORIDE SOLUTION.
AB  - 1. Direct measurements of the blood pressure carried out during the intravenous
      infusion of various solutions into rabbits show that although a relation between
      the height of blood pressure and secretion of urine may be noted, a direct
      relation docs not exist between blood pressure and peritoneal transudate and
      intestinal fluid. 2. Calcium chloride docs not increase the peritoneal transudate
      by a rise of blood pressure, nor does it decrease the intestinal fluid by a fall
      of blood pressure, since no such increase of peritoneal fluid nor decrease of
      intestinal fluid is noticeable in animals with myocarditic lesions which are
      infused with solutions of sodium chloride. 3. It can be proved that calcium
      chloride does not diminish the amount of urine as a result of its depressing
      action on the blood pressure. Our experiments make it probable that calcium
      chloride decreases the diuresis by a direct action on the renal epithelium.

PMID- 19867275
TI  - THE INFLUENCE OF CONCENTRATION (GIBSON'S METHOD) ON THE PRESENCE OF TETANUS TOXIN
      IN BLOOD SERUM.

PMID- 19867276
TI  - THE RELATIONS OF THE THYROID GLANDS TO GLYCOSURIA.
AB  - 1. After thyroidectomy the glycosuria, produced by ether or adrenalin in the
      normal animal, is greatly reduced. 2. Thyroidless dogs fed on powdered thyroid
      glands show a return of glycosuria more or less proportional to the amount
      ingested when treated with adrenalin or ether. 3. As the thyroids regenerate the
      ether or adrenalin glycosuria increases similarly. The results of these
      experiments leave no doubt in our minds that the secretion of the thyroid glands
      is connected in some obscure way with the metabolism of sugar in the body or
      exerts some control over organs whose duty it is to participate in the sugar
      metabolism.

PMID- 19867277
TI  - THE INFLUENCE OF THE THYROID ON CARBOHYDRATE METABOLISM.
AB  - 1. The thyroid exerts a retarding action on the carbohydrate destroying mechanism
      of the body. 2. This retarding action is not changed when the gland is boiled,
      showing that it is not a ferment action. 3. Iodothyrin, the active principle of
      the gland, exerts this retarding influence more markedly even than the whole
      thyroid. 4. This antagonism between the thyroid and the carbohydrate destroying
      mechanism is a direct one, as other ductless glands and the nervous system are
      eliminated from the experiments. 5. These results confirm those of Falta along
      similar lines.

PMID- 19867278
TI  - EFFECT OF THE INJECTION OF BILE ON THE CIRCULATION.
AB  - 1. We have confirmed previous work which shows that the injection of bile
      increases the tone of the vagus nerve, and that this action can be abolished
      after the administration of atropine. 2. We have found that the amount of bile
      salts in a lethal dose of pig's bile for dog's will, if inejcted alone, produce
      neither a fall in blood pressure nor a slowing in rate. 3. We have found that the
      amount of pigment in a lethal dose of the bile will, if injected alone, cause
      death with slowing of the heart and lowering of blood pressure. 4. We have found
      that the bile pigment in combination with calcium or sodium is less toxic than
      uncombined pigment. 5. We have found that in experimentally produced jaundice the
      calcium content of the blood is increased, while that of the liver, muscle and
      brain are decreased. 6. We are of the opinion that increase in calcium in the
      blood is a protective mechanism against the circulating pigments of obstructive
      jaundice.

PMID- 19867279
TI  - ENZYMES OF TUBERCULOUS EXUDATES.

PMID- 19867280
TI  - ON AUTO-ANTIBODY FORMATION AND ANTIHEMOLYSIS.

PMID- 19867281
TI  - PROTEOLYTIC ENZYMES AND ANTI-ENZYMES OF NORMAL AND PATHOLOGICAL CEREBRO-SPINAL
      FLUIDS.
AB  - The experiments which have been presented show that the spinal fluid occupies a
      unique position among the fluids which accumulate in serous cavities of the body.
      It contains normally neither proteolytic enzyme nor anti-enzyme, whereas blood
      serum, from which it is derived, exhibits both enzymotic and anti-enzymotic
      activity. In the blood anti-enzyme greatly predominates over enzyme, so that
      proteolysis does not occur, unless the anti-enzymotic power of the serum has been
      destroyed by the addition of acid. In pathological conditions both enzyme and
      anti-enzyme may make their appearance in the spinal fluid. With inflammations of
      other serous cavities of the body the anti-enzyme of the exuded serum as a rule
      preponderates over and restrains the activity of the proteolytic enzyme freed
      from leucocytes. On the other hand, in infection of the meninges with Diplococcus
      lanceolatus and with Streptococcus mucosus free proteolytic enzyme has been
      present in considerable amount in four of five fluids which have been tested.
      Free proteolytic enzyme has not been observed in the spinal fluid in cases of
      epidemic meningitis. The cases which have been studied demonstrate that in
      epidemic meningitis some anti-enzymotic action may be present in the early stages
      of the disease; but it tends to disappear rapidly so that anti-enzyme seems to be
      constantly at a low ebb. It is possible that the absence of anti-enzyme in normal
      spinal fluid, and the tendency for it to disappear so much more rapidly than in
      other inflammatory exudates, may explain in part the severity of acute meningeal
      infections. Non-inflammatory transudates into the subdural spaces differ from
      inflammatory exudates in that the inhibitory element of the blood serum
      accumulates, and this accumulation suggests an interference with the elimination
      of the antibody from the spinal fluid. Such interference is not evident in so
      called serous meningitis. In content of anti-enzyme the spinal fluid of chronic
      conditions, such as tuberculous meningitis, apparently occupies an intermediate
      position between acute inflammation and serous effusion, and five of seven
      tuberculous fluids which were tested exhibited various degrees of anti-enzymotic
      action. Variations in content of enzyme and anti-enzyme, noted above, may depend
      upon the rapidity with which the fluid, carrying the elements mentioned, enters
      the spinal cavity, as well as upon the rate of their elimination from the spinal
      fluid. Subdural injection of large quantities of anti-meningitis serum (horse's
      blood serum) does not increase the anti-enzymotic activity of fluids withdrawn
      twenty-four hours after its injection; disappearance of anti-enzyme being caused
      by rapid elimination of serum from the spinal fluid.

PMID- 19867282
TI  - EXPERIMENTAL STUDIES ON PNEUMOCOCCUS INFECTIONS.
AB  - 1. Phagocytosis of pneumococci in vitro runs parallel with phagocytosis in vivo.
      2. Virulence depends not only on resistance to phagocytosis, but also on the
      ability to grow in the body of the animal. 3. The biological reaction of the
      pigeon to pneumococcus infection does not differ from that of the mouse. 4. The
      "immunity" of the pigeon to pneumococcus infection is due to its normal high
      temperature.

PMID- 19867283
TI  - THE RESISTANCE TO A SPECIFIC HEMOLYSIN OF HUMAN ERYTHROCYTES IN HEALTH AND
      DISEASE.
AB  - 1. Phagocytosis of pneumococci in vitro runs parallel with phagocytosis in vivo.
      2. Virulence depends not only on resistance to phagocytosis, but also on the
      ability to grow in the body of the animal. 3. The biological reaction of the
      pigeon to pneumococcus infection does not differ from that of the mouse. 4. The
      "immunity" of the pigeon to pneumococcus infection is due to its normal high
      temperature.

PMID- 19867284
TI  - MECHANISM OF THE REACTION BETWEEN BILE SALTS AND BLOOD SERUM AND THE EFFECT OF
      CONJUGATION IN THE FORMATION OF BILE SALTS.
AB  - THESE EXPERIMENTS SUGGEST THE FOLLOWING CONCLUSIONS CONCERNING HEMOLYTIC ACTION:
      1. It is probably the proteid part of the serum which inhibits the bile salts. 2.
      The cholalic acid group is the active part of the bile salt molecule. 3. The
      protection afforded by bile salts against serum is of especial interest from the
      following considerations: (a) The protective action is a property apparently
      peculiar to proteids obtained from blood serum. It is not given satisfactorily by
      egg albumen. (b) The conjugation of cholalic acid with glycocoll in the formation
      of the bile salts is of some advantage to the organism. Although the toxicity of
      the cholalate for red corpuscles, when free from serum, is at most only slightly
      diminished by conjugation, yet the blood serum possesses a greater inhibiting
      action for the resulting glycocholate than for the original cholalate. 4. As
      compared with its inhibition of sodium glycocholate, normal serum possesses
      relatively little inhibiting action against certain foreign hemolytic agents,
      such as tetanus toxin, sodium benzoate, phenol and ethyl alcohol. 5. Hemolytic
      experiments afford a fairly general method for studying, in vitro, certain
      syntheses occurring in the body. They avoid, largely, the complications, such as
      rapid chemical alteration, which might occur in animal experimentation. Contrary
      to the results obtained with bile salts, the conjugation of benzoic acid and of
      phenol results in an effective reduction of their hemolytic action independently
      of the presence or absence of serum.

PMID- 19867285
TI  - THE INFLUENCE OF THYROIDECTOMY ON ALIMENTARY GLYCOSURIA.
AB  - 1. Removal of the thyroid glands causes a rise in the assimilation limit for
      dextrose. 2. If the parathyroids are left, this result is permanent. 3. The
      thyroids probably inhibit normally the direct combustion of the sugar in the
      muscles.

PMID- 19867286
TI  - THE THERAPEUTIC IMMUNITY REACTION IN THE DIFFERENTIATION OF TRYPANOSOME SPECIES.

PMID- 19867287
TI  - PARABIOSIS AS A TEST FOR CIRCULATING ANTI-BODIES IN CANCER : FIRST PAPER.

PMID- 19867288
TI  - PHAGOCYTIC IMMUNITY IN STREPTOCOCCUS INFECTIONS.
AB  - 1. In infections with streptococcus in man, such as acute septic endocarditis,
      and tonsillitis, there is produced a powerful opsonic immunity. 2. This opsonic
      immunity is effective towards the streptococcus which has caused infection but
      may be ineffective in the presence of streptococcus from other sources. 3. Little
      benefit can be expected from streptococcus vaccines unless they are prepared from
      the streptococcus which has caused infection.

PMID- 19867289
TI  - ON THE CHARACTER OF PROTEIN METABOLISM IN CHRONIC NEPHRITIS.
AB  - 1. For the study of the character of nitrogen metabolism in nephritis the
      nitrogen intake of the patient needs to he regulated in such a manner that it
      should not exceed the nitrogen value which the diseased kidneys are capable of
      eliminating. 2. The eliminating capacity of the kidneys can he established in the
      following manner: the patient is placed on a diet containing a low proportion of
      protein (equivalent to about 5 grams of nitrogen) and a sufficient supply of
      calories. To this diet from day to day varying quantities of urea are added and
      the nitrogen output for every twenty-four hours is estimated. The highest
      nitrogen output under this condition is regarded as the maximum of the
      eliminating capacity of the kidneys for nitrogenous substances. 3. In the
      observations recorded in this communication the nitrogen output of the patient on
      the standard diet remained at 5.5 grams per day. The addition to the diet of 1.5
      to 3 grams of nitrogen in form of urea caused a rise in the intake not exceeding
      6.25 grams. On the basis of this, the diet was regulated so as not to exceed a
      nitrogen intake of 7 grams. 4. Comparing the rate of elimination of nitrogen
      after the administration of glycin, alanin, and asparagin with that after the
      administration of urea, there was noted a slower rate after the administration of
      the first two acids, and an equal rate after the administration of asparagin
      (probably owing to the presence of an acid amid group in the molecule). 5. After
      the administration of excessive protein in addition to the standard diet, there
      was noted a much lower rate of nitrogen elimination than was to be expected in a
      normal man, on the basis of the work of Falta. 6. Of the total nitrogen removed
      in excess over that on the standard diet in our patient, 80 per cent. was in the
      form of urea, while in normal man, as calculated from the tables of Folin, one
      finds the proportion of urea to vary between 90 and 100 per cent., while in a
      normal dog the proportion is always 100 per cent. 7. On the basis of these
      observations it was concluded that in our patient the rate of conversion of
      protein into simple nitrogenous substances and into urea is below the normal. 8.
      The patient remained for four months in a condition of nitrogenous equilibrium,
      and otherwise in good health, on a diet containing about 6.5 grams of nitrogen
      and 3,000 calories, which were reduced to 2,500 calories to prevent constant gain
      in weight. 9. From this it seems suggestive that also for dietetic-therapeutic
      purposes it may be of importance to establish the eliminating efficiency of the
      kidneys for nitrogenous substances.

PMID- 19867290
TI  - SUPPRESSION OF ANTIBODY SYNTHESIS AND PROLONGATION OF HOMOGRAFT SURVIVAL BY
      CHLORAMPHENICOL.
AB  - Chloramphenicol suppresses primary antibody synthesis in vivo without affecting
      the ability to develop a normal anamnestic response. Chloramphenicol also
      prolongs homograft survival in rabbits. The survival of homografts is related to
      the duration as well as to the amount of chloramphenicol administered. The
      mechanism of action of chloramphenicol in suppressing immune responses is
      correlated with its ability to inhibit protein synthesis in proliferating
      mammalian cells. These observations suggest that the inhibitory effect of
      chloramphenicol on protein synthesis may be applicable to mammalian cells in vivo
      as well as to cell-free systems and to intact mammalian cells in vivo.

PMID- 19867291
TI  - THE ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES OF ARSENIC AZOPROTEINS : I.
      ANTICOAGULANT EFFECTS OF ARSENIC AZOPROTEINS IN VIVO AND IN VITRO: COMPARISON OF
      ARSENICALS AS ANTICOAGULANTS AND AS ANTILYMPHOMA AGENTS: MOLECULAR STRUCTURE IN
      RELATION TO ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES.
AB  - Experiments given in this paper have shown that 4-arsonophenylazoproteins possess
      marked anticoagulant activity both in vivo and in vitro. Mice and rabbits given
      moderate amounts of the arsenic azoprotein, for example, often bled to death from
      injuries that proved trivial in control animals, and their blood remained liquid
      during many hours' postmortem even when left in contact with transected tissues,
      fibrinolysis having no part in the outcome. So, too, the addition of minute
      amounts of 4-arsonophenylazoprotein to plasma procured from citrated rabbit or
      human blood greatly prolonged the time required for clotting after
      recalcification. Other arsenic-containing compounds,-for example, those in which
      arsenic See PDF for Structure was joined to amino acids or peptides through the
      azo linkage, or to proteins through couplings other than the azo linkage,-were
      largely devoid of anticoagulant and antilymphoma effects. The findings as a whole
      show clearly that the structural requirements for anticoagulant and antilymphoma
      effects are: (a) possession of negatively charged arsonic or arsinoso groups, (b)
      large molecular size (protein), and (c) linkage of arsenic-containing groups to
      protein through the azo bond. Two acidic azoproteins that were devoid of arsenic,
      namely 4-carboxyphenylazoprotein and 4-sulfonophenylazoprotein,-were also found
      to have marked anticoagulant effects in vitro, but they had no inhibitory action
      against cells of Lymphoma 6C3HED in vivo, even when they were given to mice in
      maximum tolerated amounts. The essential part played by arsenic in the
      antilymphoma activity of arsenic azoproteins was further emphasized by the action
      of dimercaprol (BAL) in preventing the antilymphoma effects of 4
      arsonophenylazoprotein on Lymphoma 6C3HED cells in vivo. In an associated paper
      the anticoagulant and antilymphoma effects of 4-arsonophenylazoproteins are
      studied further, and consideration is given to the ways in which these effects
      may be brought about.

PMID- 19867292
TI  - THE ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES OF ARSENIC AZOPROTEINS : II.
      COMBINATION OF ARSENIC AZOPROTEINS WITH FIBRINOGEN AND POLYMERIZING FIBRIN IN
      VITRO: ALTERATIONS IN MITOSIS OF LYMPHOMA 6C3HED CELLS INDUCED IN VIVO WITH
      ARSENIC AZOPROTEINS: DISCUSSION OF MEANS WHEREBY ARSENIC AZOPROTEINS MAY ACT UPON
      LYMPHOMA 6C3HED CELLS IN VIVO.
AB  - Experiments here given show that 4-arsonophenylazoproteins form complexes with
      fibrinogen which are resistant to the enzymic action of thrombin, coagulation
      being thus inhibited; also that arsenic azoproteins combine strongly with
      polymerizing fibrin, the reaction leading uniquely to acceleration of the
      process. Ordinary arsenicals have little or no effect on the proliferation of
      Lymphoma 6C3HED cells in vivo. 4-Arsonophenylazoproteins, by contrast, are
      strongly inhibitory, and they arrest the process of mitosis in metaphase, as does
      colchicine. Considered together with the observations of the preceding paper, the
      findings suggest that 4-arsonophenylazoproteins may exert their anticoagulant and
      antilymphoma effects by similar or related means: in the former instance, by
      combining in vitro with fibrinogen and polymerizing fibrin, thus altering the
      clotting process as mentioned above; and in the latter instance by combining,
      perhaps in a similar way, with polymerizing proteins in the mitotic spindle of
      proliferating Lymphoma 6C3HED cells, thus arresting mitosis. Further implications
      of the findings are discussed.

PMID- 19867293
TI  - QUANTITATIVE STUDIES ON THE BEHAVIOR OF SENSITIZED LYMPHOCYTES IN VITRO : I.
      RELATIONSHIP OF THE DEGREE OF DESTRUCTION OF HOMOLOGOUS TARGET CELLS TO THE
      NUMBER OF LYMPHOCYTES AND TO THE TIME OF CONTACT IN CULTURE AND CONSIDERATION OF
      THE EFFECTS OF ISOIMMUNE SERUM.
AB  - When lymphoid cells, derived from rats immunized with respect to homologous skin,
      were cultured with target cells originally of donor origin, cytocidal and
      cytostatic activities of the attacking lymphocytes became evident. By application
      of a sensitive and reproducible quantitative assay system, various aspects of the
      mechanism of this destructive interaction between target cells and lymphocytes
      were examined with the following results. 1. The degree of survival of target
      cells was inversely related to the number of sensitized lymphocytes. Graphic
      plots of the data indicated that this relationship was an exponential one similar
      to "single-hit" inactivation phenomena. One interpretation which could be placed
      on these results is that a single lymphocyte, if immunologically active, was
      sufficient to destroy or at least have a detectably adverse effect on one target
      cell. Furthermore, from such a model it could be computed that, of the
      lymphocytes derived from an immunized animal, approximately 1 to 2 per cent of
      the cells were immunologically active; i.e., capable of demonstrable destructive
      activities against homologous target cells in vitro. 2. Morphological studies on
      the effect of sensitized lymphoid cells on homologous target cells, aftervarious
      lengths of time in culture, showed that by 7 hours of incubation, the attacking
      lymphocytes firmly adhered to the target cells. The cytotoxic effect of these
      lymphocytes generally occurred after the 20th hour. Quantitative studies
      supported this conclusion; the latent period, i.e., the time required for
      detectable degrees of target cell destruction to occur, was approximately 20
      hours. 3. A consequence of the incubation of target cells with normal lymphoid
      cells or even with small numbers of sensitized lymphoid cells was an increase in
      the rate of division of the target cells. As might be expected, this was
      reflected in a shorter doubling time of these cells. 4. Extracts prepared from
      sonically disrupted sensitized lymphocytes proved to be no more deleterious to
      target cells than similar preparations from normal lymphoid cells. Furthermore,
      no evidence could be obtained that sensitized lymphoid cells, separated from
      target cells by a Millipore membrane, were cytocidally effective. These data
      indicated that if a cell-bound substance is involved in the destruction of
      homologous cells, either it is not toxic by itself, or it cannot be detached from
      the sensitized cells. In any case, close apposition of the lymphocytes to the
      target cells is apparently required for the destruction of the latter in vitro.
      5. Serum obtained from immunized animals, if heat-inactivated, did not adversely
      affect homologous target cells; if employed fresh, slight degrees of toxicity
      resulted. Specific isoimmune sera did not impart any detectable degrees of
      immunological reactivity upon otherwise normal lymphoid cells. Immune sera, even
      in high concentrations, did not augment the effect of sensitized lymphoid cells
      upon homologous target cells; rather a slight inhibitory effect of these sera was
      detected. 6. Attempts to detect the presence of complement activity, which might
      have been provided by the lymphoid cells in culture, were unsuccessful. On the
      basis of these results, it was suggested that the destruction of homologous
      target cells by sensitized lymphoid cells occurs as a two step process. First,
      the attacking lymphocytes attach to their targets via a non-toxic cell-bound
      substance having an immunologic specificity, and then, destruction of the target
      cells follows the result of some process dependent on the metabolic activity of
      the attacking lymphoid cells.

PMID- 19867294
TI  - COLICINE K : VI. THE IMMUNE RESPONSE OF HORSES TO A COLICINOGENIC STRAIN OF
      ESCHERICHIA COLI.
AB  - 1. The immunization of horses with the colicinogenic bacillus E. coli K235 L +
      O(m) stimulates antibodies which precipitate and neutralize colicine K and
      neutralize the heterologous colicine I as well. 2. Unlike rabbits, horses evoke
      predpitating antibodies for the sialic acid-containing polysaccharide colominic
      acid.

PMID- 19867295
TI  - INCREASED VASCULAR PERMEABILITY INDUCED BY HUMAN PLASMIN.
AB  - Preparations of plasminogen, soluble in aqueous media, increased vascular
      permeability in guinea pig skin when activated by streptokinase or urokinase. The
      permeability-enhancing effect was inhibited by soybean trypsin inhibitor but not
      by triprolidine. Permeability-enhancing activity evolved when plasmin was
      incubated with fractions of plasma rich in prokinin. The experiments described
      suggest that plasmin exerts its permeability-increasing effect through the
      elaboration of kinins.

PMID- 19867296
TI  - PATHOGENESIS OF THYMIC CHANGES IN NZB MICE WITH HEMOLYTIC ANEMIA.
AB  - Lymphoid follicles evolve in the perivascular connective tissue of many organs,
      including the thymuses, in NZB/Bl mice with hemolytic anemia. In previously
      published studies, these thymic follicles have been held to be causal in the
      autoimmune genesis of the hemolytic anemia. The present study contradicts this
      interpretation by demonstrating: (a) lymphoid follicles develop in the
      perivascular connective tissue of many organs in NZB mice, and are not restricted
      to the thymuses; and (b) thymic lymphoid follicles develop in aged Swiss mice
      without hemolytic anemia. Contrary to previous reports, the thymuses of NZB mice
      contain normal numbers of Hassall's corpuscles, which develop from preexisting
      thymic epithelial cells, and not from blood vessels.

PMID- 19867297
TI  - Reactivation in vitro of immunocompetence in irradiated mouse spleen.
AB  - The restoration of immunological competence to irradiated adult mouse spleen was
      studied using an in vitro assay system. Competence of the spleen to evoke a graft
      versus host reaction in vitro was lost upon sublethal irradiation (550 R).
      Regeneration of immune competence occurred when such spleens were grown for 2-3
      days in the presence of thymus tissue, but not when grown in the presence of a
      variety of other tissues. This thymic activity was demonstrated to occur across
      an intervening Millipore filter barrier. When lethal doses of irradiation were
      used, reactivation of immune competence did not occur unless both thymus and bone
      marrow were present. In this experimental situation the bone marrow appeared to
      supply the immunocompetent cells.

PMID- 19867298
TI  - The rate of release of leukocyte pyrogen from rabbit blood incubated with
      endotoxin.
AB  - The time course of leukocyte pyrogen liberation from whole rabbit blood incubated
      at 37 degrees C with various concentrations of proteus endotoxin was studied. The
      kinetics of the process provide further evidence for the view that leukocyte
      pyrogen is an independent entity. It was shown that complete liberation of all
      available leukocyte pyrogen from blood is too slow a process to account for the
      fevers seen when rabbits are injected with endotoxin. However, very small
      quantities of leukocyte pyrogen were demonstrated after short periods of
      incubation which are adequate to account for endotoxin fevers. It was also found
      that small, but definite, quantities of leukocyte pyrogen are liberated from
      rabbit blood incubated without endotoxin.

PMID- 19867299
TI  - An intestinal threadworm as a reservoir and intermediate host for Swine influenza
      virus : a confirmation and amplification of shope's syndrome.
AB  - A laboratory model exemplifying Shope's concept of virus carriage by helminths
      was developed using Strongyloides ratti (Sandground, 1925), swine influenza
      virus, and caesarean-originated, barrier-sustained (COBS) mice and rats. It was
      shown that S. ratti can act as a carrier of swine influenza virus and infect
      mice, despite the fact that the nematode has undergone a complete life cycle
      after exposure to virus in infected rats. COBS rats were inoculated with the
      virus via the intranasal route and subsequently infected with S. ratti. The
      larvae and eggs found in the feces collected from these rats were allowed to
      develop in vitro. These second generation filariform larvae were then inoculated
      subcutaneously into COBS mice. At necropsy, 5-8 days postinoculation, swine
      influenza virus was isolated from 15% of the mouse lungs. In control studies,
      swine influenza virus was not isolated from the feces of the COBS rats which
      served as a source of both unexposed and exposed S. ratti. Swine influenza virus
      was recovered in vitro from S. ratti homogenates. It is suggested that this
      laboratory model be used to study more closely the various aspects of the ecology
      of virus-helminth relationships in vertebrate hosts.

PMID- 19867300
TI  - SPONTANEOUS AMYLOIDOSIS IN DIFFERENTLY GROUPED AND TREATED DBA/2, BALB/c, AND CBA
      MICE AND THYMUS FIBROSIS IN ESTROGEN-TREATED BALB/c MALES.
AB  - Sex-segregated grouping of DBA/2, BALB/c, and CBA males caused rapid amyloid
      development and early death as compared with segregated grouped females or with
      males living individually in cages with several females. Grouping of several
      males in a cage with females also caused early death in amyloidosis indicating
      that the exposure of males to males and not the sexual isolation was important
      for the amyloid development. Both reserpine treatment and castration prolonged
      the survival time of sex-segregated grouped males. Estrogen treatment retarded
      amyloid development in sex-segregated males while spayed and androgen-treated
      spayed females showed only small amounts of amyloid. Treatment with
      chlortetracycline did not prevent amyloid development in grouped males.
      Thymectomy of sex-segregated males at 1 month of age gave inconclusive evidence
      of a prolongation of survival time. Egg-transferred DBA/2 mice reacted as
      conventional DBA/2 mice when grouped by sex segregation. Cells with abundant PAS
      positive cytoplasm were found in the spleen, liver, and ovaries of mice of all
      strains but most prominently in CBA mice. Evidence for a direct conversion of
      these cells to amyloid was found. Estrogen-treated BALB/c males developed
      testicular tumors and thymus alterations including necrosis and depletion of
      lymphocytes, depletion of PAS cells, formation of large cysts containing necrotic
      nuclei, and intralobular fibrosis.

PMID- 19867301
TI  - Antibodies to intestinal microvillous membranes : ii. Inhibition of intrinsic
      factor-mediated attachment of vitamin b(12)to hamster brush borders.
AB  - Microvillous membranes isolated from the distal, but not proximal, half of
      hamster small bowel induced in rabbits the formation of antisera which inhibited
      intrinsic factor-mediated uptake of vitamin B(12) by hamster brush borders. The
      extent of inhibition was directly proportional to the concentration of antiserum,
      and an excess of IF-bound vitamin B(12) could overcome the inhibitory effect. The
      inhibitory factor was absorbed from antisera by brush borders isolated from the
      distal, but not proximal, half of the hamster intestine. Fractionation of
      antisera by gel filtration and DEAE-cellulose chromatography established that
      immunoglobulin G contained the inhibitory factor. Antisera capable of completely
      blocking uptake of IF-bound vitamin B(12) did not react with hamster IF or with
      the IF-vitamin B(12) complex, did not inhibit brush border disaccharidase
      activity and did not impair glucose transport by everted sacs of hamster
      intestine. These results demonstrate that an antibody to distal microvillous
      membranes competes with the IF-vitamin B(12) complex for a specific binding site
      or receptor located on the surface of distal hamster intestine.

PMID- 19867302
TI  - Quantitative assay of antigenic disparity at hl-a-the major histocompatibility
      locus in man.
AB  - We have extended the method of one-way stimulation in mixed leukocyte culture
      tests as previously described to quantitate different degrees of stimulation. To
      demonstrate that the amount of stimulation is immunogenetically meaningful,
      siblings and parents in families in whom genotyping on the basis of leukocyte
      antigen data was possible were tested. The prediction that cells of siblings
      differing from the responding sibling by both alleles at HL-A, stimulate more
      than do cells of siblings differing by only one allele, was realized in every
      case. One exception, with cells of a parent, is discussed. It is stressed that
      the differences measured here are probably fairly strong ones in the majority of
      cases, and that lesser differences cannot yet be detected reproducibly.

PMID- 19867303
TI  - Cellular events in the immune response : analysis and in vitro response of mouse
      spleen cell populations separated by differential flotation in albumin gradients.
AB  - Cell suspensions from the spleens of normal mice or mice injected with sheep
      erythrocytes were separated on a discontinous bovine serum albumin density
      gradient. Four bands or subpopulations were obtained and were assayed for
      antibody-forming cells, and for antigen-sensitive precursor cells. The antibody
      forming cells were assayed by the hemolytic plaque assay and the antigen
      sensitive precursors were assayed by the number of plaque-forming cells which
      developed after 3 or 5 day's culture with antigen. It was found that both
      antibody-forming cells and their precursors were present in the denser region of
      the gradient when spleen cell suspensions were taken from unimmunized mice. In
      contrast, both antibody-forming cells and precursors floated to the top in cell
      suspensions from mice sacrificed 1, 2, or 3 days after antigen injection. The
      change in density was detectable as early as 12 hr and was complete by 18 hr. The
      cell which changed in density was specific for the antigen that brought about
      that change. The significance of these findings is discussed.

PMID- 19867304
TI  - CHEMICAL CHARACTERIZATION OF GLYCOPEPTIDES FROM HUMAN gammaM-GLOBULINS.
AB  - A survey of human pathological macroglobulins revealed that gammaM can be divided
      into at least two groups on the basis of carbohydrate composition. Differences
      between the two groups exist in the total percentage of carbohydrate (10.69 +/-
      1.49% for group 1, 7.71 +/- 0.65% for group II) which is attributable to
      variation in hexose content. Glycopeptides from macroglobulins of each group were
      purified from pronase digests and characterized chemically. Macroglobulins from
      each group contain three types of oligosaccharides. Glycopeptide I for each group
      consisted of mannose, galactose, and NAG with a ratio of 3:2:1 for group I and a
      ratio of 2:1:2 for group II. Glycopeptide II consisted of mannose, galactose, and
      NAG (9:1:2) for group I, and mannose, fucose, galactose, and NAG (2:1:3:2) for
      group II. Glycopeptide III in both groups consisted of mannose, fucose,
      galactose, NAG, and sialic acid with a ratio of 6:2.5:2.5:5.5:2 for group I and a
      ratio of 5:1:1:6:1 for group II. Molecular weight estimations by gel filtration
      indicates that there are 10 glycopeptides I and II and 20 units of glycopeptide
      III per molecule of gammaM.

PMID- 19867305
TI  - FURTHER STUDIES ON THE gammaG-HEAVY CHAIN GENE COMPLEXES, WITH PARTICULAR
      REFERENCE TO THE GENETIC MARKERS Gm(g) AND Gm(n).
AB  - The recently described Gm (g) and Gm (n) genetic markers of the gammaG3- and
      gammaG2-subgroups of gamma-globulin were characterized in detail primarily
      through studies of myeloma proteins, their polypeptide chains and fragments.
      Antisera derived from rabbits, non-human primates and rheumatoid arthritis
      patients gave identical results. This contrasted with the Gm (b) system where the
      rabbit antisera react with a different genetic determinant (b(0)) than the sera
      from rheumatoid arthritis patients (b). The Gm (g) and Gm (n) antigens were
      detected both by precipitin analysis and by hemagglutination inhibition. The Gm
      (g) antigen was not associated with any of the other genetic antigens of the
      gammaG3-proteins which all belonged in the Gm (b) class. The genes for the latter
      were always allelic to the gene coding for Gm (g), with that for Gm (b(0))
      constantly present when that for Gm (g) was absent. The Gm (g) and Gm (n) markers
      were of particular value in tracing the various gene complexes made up of the
      closely linked subgroup genes. Further support was gained for the concept that
      the different gene complexes of various population groups arose primarily through
      crossing-over. The Gm(g) and Gm(b) genes for the gammaG3-subgroup were extremely
      closely linked to those for the gammaG1-subgroup. However the Gm (n) marker
      indicated that the gammaG2-subgroup genes were probably further separated on the
      chromosome. Additional evidence was obtained for the gammaG2-gammaG3-gammaG1
      order of the subgroup cistrons. Among the wide range of gene complexes a new type
      (gammaG2,-,gamma/G1) was described. This complex appeared to have a deletion of
      the gammaG3-cistron. Lower levels of gammaG3-globulin were found in the sera of
      the individuals with this gene in the heterozygous state. The possibility that
      this unusual complex arose through an unequal nonhomologous crossing-over is
      discussed.

PMID- 19867306
TI  - ON THE RELATION OF THE CATALYTIC ACTIVITY OF THE BLOOD TO THE NUMBER OF RED BLOOD
      CELLS IN HEALTH, AND TO THE NUMBER OF WHITE BLOOD CELLS AND THE BODY TEMPERATURE
      IN PERITONITIS.
AB  - The catalytic activity of the blood of normal rabbits varies almost directly with
      the volume and number of red blood cells. This explains to a certain extent at
      least why animals of the same general degree of nutrition, and of the same
      litter, should have about the same activity since they are likely to have the
      same number of red blood cells, and why healthy large animals should read high
      while small poorly nourished ones should read low. Accompanying the hyperpyrexia
      resulting from puncture of the corpus striatum of a rabbit's brain, there is no
      change in either the catalytic activity of the blood or the white blood count. In
      experimentally produced peritonitis, the catalytic activity of the blood always
      rises, and is, therefore, absolutely independent of body temperature and white
      blood cells since one or both of these may rise, fall or remain stationary while
      the catalytic action increases.

PMID- 19867307
TI  - THE INFLUENCE OF ADRENALIN IN PHLORHIZIN DIABETES.
AB  - I. Intraperitoneal injections of adrenalin into animals which are completely
      under the influence of phlorhizin and which are free from glycogen do not result
      in any extra elimination of sugar. This proves that adrenalin does not cause a
      conversion of fat into carbohydrates, as is maintained by Blum and by Eppinger,
      Falta and Rudinger. II. The high D:N ratio 5.2 and 6.1 reported by Eppinger,
      Falta and Rudinger after adrenalin injections in depancreatized dogs, which were
      obtained after short periods of six hours and four hours respectively, can be
      explained by the elimination of carbohydrates present in the organism. III. These
      results confirm the work of Straub and Ritzmann which indicates that adrenalin,
      by its constricting effect on the blood vessels, produces anemia of the tissues,
      resulting in imperfect oxidation, and this anemia is followed by the conversion
      of glycogen into dextrose by hyperglycemia and consequently by glycosuria.

PMID- 19867308
TI  - THE CATALYTIC ACTIVITY OF THE DEVELOPING HEN'S EGG.
AB  - A. The catalytic activity of the tissues of newly born and adult rabbits. 1.
      There is practically no difference between the catalytic power of the blood,
      brain or muscle of newly born and adult rabbits. 2. The kidneys and lungs are
      less active in the newly born, but increase rapidly during the first days of
      life. 3. The liver is more active in the newly born than in the adult rabbit. B.
      The catalytic activity of the developing hen's egg. 1. The entire fresh egg has a
      slight but definite catalytic power which remains practically constant even
      though the egg be kept for several months at room temperature. 2. The separate
      parts of the egg, germinal center, yolk and white have practically no activity
      when tested individually. 3. The entire unfertilized egg shows no catalytic
      activity even after incubation at 38 degrees C. for twenty-one days. 4. The
      germinal portion of the incubated fertilized egg rapidly acquires the power of
      decomposing hydrogen peroxide, while the yolk and white together or separately
      show no such increase, nor is there any activity to be found in the amniotic
      fluid. 5. It seems, therefore, that the catalytic power of the developing egg is
      formed from the contents of the egg which themselves show little action, by the
      developing germinal portion, independent of all external influences except heat
      (38 degrees C.) and air.

PMID- 19867309
TI  - EXPERIMENTAL SARCOSPORIDIOSIS IN THE GUINEA-PIG AND ITS RELATION TO A CASE OF
      SARCOSPORIDIOSIS IN MAN.
AB  - 1. Guinea-pigs, naturally uninfected by sarcosporidia, were infected by feeding
      them with rat's muscle that was naturally infected by Sarcocystis muris, and by
      ripe mobile sporozoites from the same source. The infection was not visible
      grossly, but was detected upon very careful search through many sections of
      muscle. 2. Sarcosporidia were not found in the guinea-pigs until after an
      interval of 164 days from the first feeding, or 152 days after the most favorable
      feeding, when many teased-out mobile sporozoites were fed. 3. The prolonged
      period of incubation or latency, and the greater time required for infection of
      guinea-pigs here over that required by Negri (7) in Pavia, may be related to the
      fact that the experiment here was conducted in the tropics where the guinea-pig
      is a native. 4. Sarcosporidia of this apparently abortive type in unusual hosts
      cannot be specifically identified until their derivation and host relationships
      have been determined. 5. Morphologically, the guinea-pig sarcosporidia derived
      from Sarcocystis muris are identical with those found by the writer in the biceps
      of a Barbadian negro, and both probably represent abortive or aberrant forms.

PMID- 19867310
TI  - RESISTANCE PRODUCED IN MICE AGAINST TRANSPLANTED CANCER BY AUTO-INOCULATION OF
      THE SPLEEN.

PMID- 19867311
TI  - THE RESPIRATORY CHANGES OF PRESSURE AT THE VARIOUS LEVELS OF THE POSTERIOR
      MEDIASTINUM.
AB  - The changes of the respiratory pressure within the esophagus, as well as within
      the posterior mediastinum, differ greatly in their various levels. They are best
      in the section between the heart and the diaphragm; they are moderate from the
      upper aperture of the thorax to above the tracheal bifurcation, and they are.
      very much reduced in the region of the bifurcation and the heart. In the latter
      case the normal respiratory changes are reduced in their transmission to the
      mediastinum by the intervention of the inelastic tissues of the bifurcation and
      the heart. The difference in the changes of the respiratory pressure between the
      low;er and the upper part of the mediastinum is due to a difference in the
      respiratory changes of pressure between the lower and upper parts of the lungs.
      The changes in the respiratory pressure which begin in the lower part of the
      lungs lose some of their force on their way to the apices of. the lungs. In
      artificial respiration by intratracheal insufflation there is no difference in
      the respiratory pressures between the upper and the lower parts of the lungs.
      This investigation supports the view, frequently entertained by clinicians, that
      the respiratory changes in the apices of the lungs are not as good as those of
      the rest of the lungs, and it disproves the claim of some physiologists that a
      decrease or increase of pressure at any part of the lungs must be equally
      distributed through all parts of the lungs, a claim based upon merely a priori
      physical considerations.

PMID- 19867312
TI  - THE EXCRETION OF CALCIUM AND MAGNESIUM AFTER PARATHYROIDECTOMY.

PMID- 19867313
TI  - THE DEXTROSE CONSUMPTION BY THE ISOLATED PERFUSED HUMAN HEART.

PMID- 19867314
TI  - AN EXPERIMENTAL STUDY OF OPSONIC IMMUNITY TO STAPHYLOCOCCUS AUREUS.
AB  - 1. The administration of Staphylococcus aureus, killed by heat (vaccine),
      produces a high degree of opsonic immunity in rabbits. 2. Such increase of
      opsonin affords protection against living virulent staphylococcus in direct
      proportion to the amount of opsonins present in the serum and complete recovery
      may follow subsequent inoculation, if the opsonic power be high. 3. Frequent
      administration of vaccines may produce a diminution of the opsonic power of the
      serum. 4. Immune opsonins are most active against the homologous strain of
      Staphylococcus aureus, but are only slightly less active against heterologous
      strains. 5. Infections of the human body by Staphylococcus aureus may cause great
      increase of opsonins. 6. Vaccines prepared from Staphylococcus aureus may produce
      a high degree of opsonic immunity in man.

PMID- 19867315
TI  - TUBERCULOUS CERVICAL ADENITIS: A STUDY OF THE TUBERCLE BACILLI CULTIVATED FROM
      FIFTEEN CONSECUTIVE CASES.
AB  - The examination of fifteen consecutive cases of primary tuberculous cervical
      adenitis resulted in the isolation of nine cultures of B. tuberculosis of bovine
      type and six cultures of human type, the classification being made on the basis
      of adaptability to artificial cultivation, character of growth on glycerine
      bouillon, virulence for rabbits, and, in three instances, virulence for calves.
      The results of the determination of the reaction changes in glycerine bouillon
      due to the growth of the cultures on this medium were in general accord with the
      classification as based on other characters. One culture otherwise of human type
      was found to give the slightly acid or even alkaline end reaction characteristic
      of the bovine type of bacillus. One culture, otherwise of bovine type, has so far
      given an end reaction more highly acid than is usual with bovine cultures. Two
      cultures, highly virulent for rabbits, showed even less adaptability to
      artificial cultivation than the usual true bovine cultures and the reaction
      change could not, therefore, be determined.

PMID- 19867316
TI  - THE INFLUENCE OF VARIOUS ORGANS ON THE CATALYTIC ACTIVITY OF THE BLOOD.

PMID- 19867317
TI  - CONCERNING THE DEPRESSOR SUBSTANCE OF DOG'S URINE AND ITS DISAPPEARANCE IN
      CERTAIN FORMS OF EXPERIMENTAL ACUTE NEPHRITIS.

PMID- 19867318
TI  - PERITONEAL PATCHING OF THE AORTA.

PMID- 19867319
TI  - REMOTE RESULTS OF THE REPLANTATION OF THE KIDNEY AND THE SPLEEN.

PMID- 19867320
TI  - THE PHYSIOLOGY OF THE IMMEDIATE REACTION OF ANAPHYLAXIS IN THE GUINEA-PIG.
AB  - 1. By an immediate anaphylactic reaction we mean the chain of symptoms which
      occur in highly sensitized guinea-pigs shortly after an intravenous or
      intracardiac injection of the toxic dose and usually end in death. 2. Immediate
      anaphylactic death occurs three to five minutes after the toxic injection in
      highly sensitized guinea-pigs. 3. Immediate anaphylactic death in guinea-pigs is
      caused by asphyxia; cessation of respiration is secondary to this asphyxia. 4.
      This asphyxia is apparently produced by a tetanic contraction of the smooth
      muscles of the bronchioles, which occludes their lumen gradually, so that finally
      no air enters or leaves the lung, in spite of violent respiratory efforts; the
      animal is strangulated. 5. The stage of complete broncho-constriction is preceded
      by a short broncho-dilatation, if the bronchioles have been in a state of tonus
      previous to the injection of the toxic dose. 6. Anatomically, the lungs of these
      guinea-pigs are typical and may be used as an indicator of the immediate
      anaphylactic state when the animal has been immobilized by curarin or by pithing.
      7. The lungs of a guinea-pig killed by immediate anaphylaxis are distended and in
      an inspiratory position so that the diaphragm is pushed down; no marked collapse
      occurs when the chest is opened and when the lungs are excised in toto; their
      color is a pale bluish-pink ; the surfaces and borders are smooth; no foam is in
      the trachea or large bronchi; pieces of lung cut off do not collapse, float
      lightly on water, and contain a good amount of air and little fluid which escapes
      on pressure. The blood in the lungs and heart is black when the autopsy is made
      at once after the cessation of respiration. 8. Section of the vagi in the neck,
      or curarin (artificial respiration) exerts no appreciable effect on the
      development of immediate anaphylaxis. 9. This immobilization of the lungs, which
      is due to a broncho-constriction, is of peripheral origin, for destruction of the
      spinal cord and medulla affects in no appreciable way the promptness and extent
      of the typical lung response to the injection of the toxic dose. Artificial
      respiration is, of course, necessary. At the present time we do not care to state
      whether the toxic dose exerts its effects upon the bronchial muscles alone or
      upon the vagus motor endings or upon both structures. 10. The blood pressure in
      immediate anaphylaxis first shows a rise, which may be considerable; a short
      maintenance of this high level and then a gradual drop to IO to 20 millimeters of
      mercury and even less, within ten minutes after injection of the toxic dose. 11.
      Shortly after injection of the toxic dose a heart block develops, so that
      auricles and ventricles may beat in a 3:I rhythm; the block is probably due to
      asphyxia. 12. The cardiac vagus gradually loses its irritability after injection
      of the toxic dose. 13. Cooling of the guinea-pig delays the reaction to the toxic
      injection.

PMID- 19867321
TI  - AN ATTENUATED SURRA OF MAURITIUS WITH IMMUNITY TESTS AFTER RECOVERY.
AB  - Apparently as a result of repeated passages through guinea pigs, the virulence of
      surra of Mauritius for mice became greatly attenuated. Three mice recovered
      spontaneously and two remained carriers of tryanosomes for four to seven weeks
      after the parasites were last seen in their blood. The mice that recovered
      acquired no lasting immunity. While the virulence of the parasites decreased for
      mice, it increased for guinea pigs. By cultivating the parasites in mice the
      virulence for these animals was restored after four to eight passages.

PMID- 19867322
TI  - PLEOMORPHISM AND PLEOBIOSIS OF BACILLUS BIFIDUS COMMUNIS.
AB  - From the foregoing experiments, the conclusion may be drawn that B. bifidus
      communis of Tissier has an aerobic phase, in which it resembles B. mesentericus
      fuscus. Numerous intermediate phases can occur between these two extremes; and
      their morphological and biological variabilities demand the utmost attention in
      order to interpret more intelligently the various phases of a given organism,
      constantly found in the stools of sucklings, and to avoid the artificial creation
      of two or more organisms from a single microbic type.

PMID- 19867323
TI  - EXPERIMENTAL ACUTE NEPHRITIS: THE VASCULAR REACTIONS AND THE ELIMINATION OF
      NITROGEN.
AB  - By combining physiological and anatomical methods in the study of experimental
      nephritis it is possible to distinguish types of nephritis in which either
      tubular or vascular changes predominate, and are essentially characteristic of
      the lesion produced, but it is not possible to say that a given poison produces
      exclusively tubular or exclusively vascular lesions. The so-called epithelial
      poisons (potassium chromate, uranium nitrate and corrosive sublimate) present
      anatomical evidence of extensive tubular injury, and in the early stages show, on
      physiological study, no evidence of vascular injury other than exaggerated
      contraction and dilatation of the vessels and increased diuresis. On the other
      hand, the vascular poisons, arsenic and cantharidin, which produce but little
      injury to the tubules, tend to cause anuria and are characterized by minimal
      contraction and dilatation of the vessels and little or no flow of urine. From
      the physiological point of view these two types may be, for practical purposes,
      considered as examples of tubular and vascular nephritis. They are not, however,
      pure types; for the increased diuresis of the early tubular type is in itself
      evidence of vessel irritability and similar to the increased irritability caused
      by small doses of vascular poisons, and on the other hand, this essentially
      vascular lesion is accompanied by slight morphological changes in the tubular
      epithelium. Furthermore, the tubular lesions of chromium and uranium and
      corrosive sublimate pass into a stage closely resembling the vascular type, if
      not identical with it. Two forms of late tubular nephritis may be recognized. One
      of these, the anuric form, is accompanied by severe gastro-intestinal disturbance
      and evidence of approaching anuria; physiological tests show diminished power of
      dilatation of the vessels and corresponding inhibition of diuresis. The second
      form, the polyuric, is characterized by a condition of polyuria up to the moment
      of anesthesia; physiological tests show that the power of dilatation is retained,
      but little or no diuresis occurs. Whether the vascular incompetency of the anuric
      form of late tubular lesions is a natural consequence of the vessel irritability
      seen in the early stages or is the result of the elimination of secondary poisons
      through the glomeruli cannot be absolutely determined. The peculiar
      impermeability of the glomerulus following anesthetization in the polyuric form,
      which is essentially a stage of recovery, we hope to explain by investigations
      now in progress. Studies of the elimination of nitrogen show that in tubular
      nephritis, as represented by uranium nephritis, the output of nitrogen is
      considerably diminished. This apparently occurs also in chromate nephritis but is
      not clearly demonstrated. In both forms the onset of gastro-intestinal
      disturbances appears to bear a definite relation to the retention of nitrogen. On
      the other hand, as the nitrogen of the feces is not appreciably altered, these
      disturbances cannot be explained by the elimination through the intestine of
      toxic bodies of nitrogenous nature. The nitrogen elimination in the urine in
      vascular nephritis as represented by arsenic nephritis is not only not diminished
      but is greatly increased as the result of the increased metabolism caused by
      arsenic. If at the height of this increased elimination, uranium nitrate is
      administered, the nitrogen output is markedly diminished. These observations
      demonstrate that not only are the tubular lesions in arsenic nephritis of little
      moment, but also that serious injury of the epithelium, as that due to uranium,
      may cause a temporary nitrogen retention. A consideration of all the facts here
      presented allows us to conclude that although it is not possible to demonstrate
      that an experimental nephritis may be purely tubular or purely vascular, which is
      in accord with our clinical and pathological studies of human material, it is
      possible, if we combine the results of anatomical, physiological and chemical
      study, to recognize lesions which are predominantly tubular or vascular, or which
      change rather sharply from one to the other type, and are, therefore, of great
      value in the study of the problems of nephritis.

PMID- 19867324
TI  - EXPERIMENTAL EPIDEMIC POLIOMYELITIS IN MONKEYS.
AB  - The experimental study of poliomyelitis has yielded a large number of important
      facts relating to the spontaneous disease in man. The nature of the virus has
      been discovered, many of its properties have been ascertained, some of its
      immunity effects have been established, the clinical and pathological
      peculiarities of the disease have been elucidated, and a basis has been secured
      on which to develop measures of prevention.

PMID- 19867325
TI  - STUDIES ON THE VENOUS PULSE. I : A STUDY OF THE DIASTOLIC WAVES OF THE VENOUS
      PULSE, WITH ESPECIAL REFERENCE TO THE POSSIBILITY OF A WAVE DUE TO THE
      CONTRACTION OF THE VENOUS REGION OF THE MAMMALIAN HEART.
AB  - A wave is described occurring in the venous pulse of man late in the diastolic
      period. This wave is a diastolic wave, since in an increase in length of the
      cardiac cycle it follows the h wave at its regular interval and becomes separated
      from the a wave of the next cardiac cycle. There is no wave on the venous pulse
      in man which can be referred to a contraction of the region of the great veins or
      sinus region of the heart. The h wave is a normal occurrence in the venous pulse
      curve from man and the dog. It occurs, according to the experience in this work,
      in all normal individuals in which the heart rate is sufficiently slow to prevent
      its obliteration by the a wave. The x wave, while not infrequent, is not always
      present in man even when the cardiac cycle is of sufficient length to prevent its
      obliteration by the a wave. This wave has not been observed in the dog. There is
      no wave on the venous pulse curve of the dog that can be referred to a
      contraction of the sinus region of the heart. Extra-systoles from stimulation of
      the venous region of the dog's heart produce no contraction of this region
      sufficiently pronounced to be recorded on a venous pulse tracing. After an
      interval of from 0.07 to 0.I second, representing the interval of veno-auricular
      conduction plus the latent period of the auricle, the auricle contracts.
      Extrasystoles from stimulation of the right auricle show, after an interval
      following the stimulus much shorter than that noted above and representing the
      latent period of the auricle, an a wave followed by ventricular systole after the
      usual a-c interval. It would seem probable that the sinus region of the heart,
      while capable of irritability, conductivity and rhythmicity (Erlanger and
      Blackman (I6)), does not normally manifest contractility.

PMID- 19867326
TI  - SURVIVAL OF ENGRAFTED TISSUES : I. (A) OVARIES AND (B) TESTICLES.

PMID- 19867327
TI  - THE CHANGES IN THE VENOUS BLOODFLOW ON ADMINISTRATION OF AMYL NITRITE.

PMID- 19867328
TI  - CHANGES INDUCED IN THE BLOOD OF RABBITS BY LIVING IN AN ATMOSPHERE OF WATER GAS.
AB  - 1. Rabbits living in an atmosphere of carbon monoxide react in general as guinea
      pigs react. 2. The increased specific gravity of the blood in " carbon monoxide "
      rabbits is due wholly to the increase in the number of erythrocytes and of
      hemoglobin, and not to any change in the plasma. 3. Weigert's law of inertia,
      that production would continue after the stimulus has ceased to act, does not
      hold in the case of carbon monoxide stimulated rabbits. 4. Hemolysins,
      precipitins and agglutinins towards normal rabbit corpuscles and sera were not
      present in carbon monoxide rabbits. 5. " Hemopoeitin " or anything of a similar
      nature was not found in rabbits in any stage of erythrocyte degeneration or
      regeneration.

PMID- 19867329
TI  - STUDIES IN EDEMA : VI. THE INFLUENCE OF ADRENALIN ON ABSORPTION FROM THE
      PERITONEAL CAVITY, WITH SOME REMARKS ON THE INFLUENCE OF CALCIUM CHLORIDE ON
      ABSORPTION.
AB  - 1. Adrenalin injected intraperitoneally increases the rapidity of absorption of
      fluid from the peritoneal cavity, independently of whether the solution to be
      absorbed is hypotonic or hypertonic or is approximately isotonic with the blood
      serum. The intravenous injection of adrenalin also increases the absorption of
      fluid, but not so markedly as does the intraperitoneal injection. 2. Adrenalin
      injected either intraperitoneally or intravenously increases the quantity of
      sodium chloride absorbed. The relative absorption of sodium chloride-the movement
      from the peritoneal cavity of sodium chloride, as compared with the movement of
      water-is slightly increased when 0.85 per cent. of sodium chloride solution and
      adrenalin are injected intraperitoneally; but it is diminished when adrenalin is
      injected intravenously, or when 1.5 per cent. sodium chloride solution and
      adrenalin are injected. When distilled water has been injected intraperitoneally,
      adrenalin decreases the relative amount of sodium chloride in the peritoneal
      fluid-a fact that is evidently related to the increased elimination of sodium
      chloride through the kidneys under the influence of adrenalin. 3. When 0.85 per
      cent. sodium chloride solution is injected into the peritoneal cavity, the blood
      becomes diluted after two hours and a half. When adrenalin is also injected, the
      dilution of the blood is less marked, in spite of the increased absorption under
      the influence of adrenalin. When distilled water is injected into the peritoneal
      cavity, the blood is diluted equally in control and adrenalin experiments. When
      1.5 per cent. sodium chloride solution is injected, the dilution of the blood is
      very slight, and in adrenalin experiments it is the same as in control
      experiments or very slightly greater than in control experiments. 4. The increase
      of absorption from the peritoneal cavity caused by the injection of adrenalin is
      not due to the increased diuresis caused by the injection of this substance. 5.
      The injection of adrenalin causes a temporary increase in the osmotic pressure of
      the blood, which gradually returns to normal. Under certain conditions, after the
      injection of adrenalin, there is a tendency toward maintaining the higher osmotic
      pressure of the blood serum, even up to the end of the experiment. We have reason
      to believe that this increase in the osmotic pressure of the blood is the main
      factor in increasing the absorption of fluid from the peritoneal cavity. 6. In
      experiments in which 0.85 per cent. sodium chloride solution has been injected
      intraperitoneally, either with or without adrenalin, there exists a tendency of
      the peritoneal fluid to attain a greater osmotic pressure than the blood serum,
      in spite of the fact that the injected fluid is slightly hypotonic as compared
      with the blood serum. We note a similar condition in cases of general edema in
      man, in which the osmotic pressure of the ascitic fluid is greater than that of
      the other edematous fluids, or even that of the blood serum. There exists,
      therefore, a mechanism that causes the passage of osmotically active substances
      from the blood or from the tissues into the peritoneal cavity, and that causes
      the osmotic pressure of the peritoneal fluid to become higher than that of the
      blood. It follows from our experiments that this mechanism, which causes the
      ascites in edematous persons to have such a high osmotic pressure, is not
      dependent upon certain pathological changes in the lining membranes or upon other
      pathological conditions, but exists already in normal animals. 7. The addition of
      1.22 per cent. calcium chloride solution to 0.83 per cent. sodium chloride
      solution, in such proportions as we used in our infusion experiments, in which we
      determined the transudation into the peritoneal cavity, delays the absorption of
      fluid from the peritoneal cavity but very slightly. Therefore, calcium chloride
      increases directly the transudation into the peritoneal cavity and does not cause
      an increase in the amount of fluid in the peritoneal cavity merely by inhibiting
      the absorption. 8. It follows that adrenalin does not increase the amount of
      peritoneal transudate found after the intravenous infusion of large quantities of
      sodium chloride solution, to which adrenalin has been added, by delaying the
      absorption from the peritoneal cavity. The increased amounts of peritoneal fluid
      must be due to increased transudation into the peritoneal cavity; and the
      adrenalin, in view of its marked effect on absorption from the peritoneal cavity,
      must increase the movement of fluid into the peritoneal cavity much more strongly
      than could be assumed from the figures obtained in the infusion experiments.

PMID- 19867330
TI  - OBSERVATIONS AND EXPERIMENTS ON THE SO-CALLED THYROID CARCINOMA OF BROOK TROUT
      (SALVELINUS FONTINALIS) AND ITS RELATION TO ORDINARY GOITRE.
AB  - Is this thyroid hyperplasia true carcinoma? In view of the facts that young fish
      are more affected than old fish, that iodin stops the hyperplasia and causes it
      to return to the colloid state, that removal of the fish from the ponds to the
      open brook also affects a cure, that the clinical incidence of tumors is directly
      related to the water supply, and that the severity of the disease as determined
      by histological examination is likewise directly related to the water supply, we
      cannot accept the prevailing opinion that the disease is true cancer. On the
      other hand, we believe that the disease as studied by us is an extreme
      illustration of endemic goitre, the end stage of which is cretinism. The opinion
      that it is cancer is based purely on anatomical studies-the essential fact being
      that the growing thyroid invades bone, muscle, etc. Such findings in mammalian
      tissues are strong evidence of malignancy, but this standard cannot be applied to
      fish thyroids for the reason that any growth of a widely and loosely distributed
      nonencapsulated gland would give the histological appearance of invasion of the
      surrounding tissues. The general views as to the cause of the disease may be
      divided into two groups: (I) infectious and (2) metabolic. Taking up the
      infectious theory, there are abundant grounds for such a view when one considers
      the flora of the tank. The very careful histological examinations by Hofer,
      Bonnet and Pick have yielded uniformly negative results. Direct infection cannot
      be excluded, but the fact that fish placed in the tail-race recover
      spontaneously, although living in the theoretically most polluted water, is not
      in harmony with our present conception of water-borne infection. Taking up the
      metabolic theory, the three factors of overfeeding, overcrowding and limited
      proportional water supply together with the many possibilities into which they
      are divisible seem to us to be in some way, still obscure, directly concerned
      with the development of the disease. It is not probable that a single substance,
      whether the result of food decomposition or of excretory products, excites the
      thyroid to its activity but rather that the thyroid reaction is the result of the
      activity of a great variety of these products.

PMID- 19867331
TI  - THE COMPLEMENT BINDING TEST IN RABIES.

PMID- 19867332
TI  - AN EXPERIMENTAL COMPARISON OF TRANSPLANTED TUMOR AND A TRANSPLANTED NORMAL TISSUE
      CAPABLE OF GROWTH.
AB  - The present paper deals with a comparison of the conditions which determine the
      fate of transplanted tumor and of a transplanted normal tissue capable of growth.
      Mouse embryo and mouse-tumor were employed as material. It was shown that
      individuals differ as hosts for transplanted embryo, some being naturally
      resistant to its growth, and some favorable, just as is known to be the case
      where tumor is concerned. The fate of implanted tumor depends directly on whether
      it elicits from the host a vascularizing stroma. So, too, it is with implanted
      embryo. Furthermore mouse-embryo, like mouse-tumor, when introduced into rats
      calls forth a stroma and grows for a brief period. In attempt to answer the
      question as to whether individuals favorable (or resistant) to implanted tumor
      are likewise favorable (or resistant) to implanted embryo, it was shown that the
      factors of age, nutritive condition, and race, which are potent in determining an
      animal's status as a tumor-host, act similarly in determining that for embryo.
      Using embryonic tissue and a method which has proven effective for the production
      of immunity to implanted tumor, an immunity to implanted embryo was brought
      about. This immunity manifests itself in the same way as that for implanted
      tumor, namely, by an absence of the stroma-reaction necessary to life of the
      engrafted tissue. These results demonstrate how largely tumor obeys in its
      adaptation to a new host and growth therein, the general laws regulating a
      transplanted normal tissue. Besides the phenomena here dealt with many others
      that have held the attention of workers with transplantable tumors are probably
      not peculiar to neoplasm. The present findings emphasize the importance of the
      tumor-problem as a tissue-problem; and they further indicate how essential it is
      in cancer work to discriminate between characters unique with tumor and those
      which it possesses in common with normal tissue.

PMID- 19867333
TI  - ON THE RELATION OF COMBINED INTOXICATION AND BACTERIAL INFECTION TO NECROSIS OF
      THE LIVER, ACUTE YELLOW ATROPHY AND CIRRHOSIS.

PMID- 19867334
TI  - STUDIES ON WATER DRINKING : II. THE METABOLIC INFLUENCE OF COPIOUS WATER DRINKING
      WITH MEALS.
AB  - The daily drinking of three liters of water with meals, for a period of five
      days, by a man twenty-two years of age who was in a condition of nitrogen
      equilibrium through the ingestion of a uniform diet, was productive of the
      following findings : 1. An increase in body weight, aggregating two pounds in
      five days. 2. An increased excretion of urinary nitrogen, the excess nitrogen
      being mainly in the form of urea, ammonia, and creatine. 3. A decreased excretion
      of creatinine and the coincident appearance of creatine in the urine. The
      decreased creatinine output is believed to indicate that the copious water
      drinking has stimulated protein catabolism. The appearance of creatine is
      considered evidence that the water has caused a partial muscular disintegration
      resulting in the release of creatine, but not profound enough to yield the total
      nitrogen content of the muscle. The output of creatine is, therefore, out of all
      proportion to the increase in the excretion of total nitrogen. 4. An increased
      output of ammonia which is interpreted as indicating an increased output of
      gastric juice. 5. A decreased excretion of feces and of fecal nitrogen, the
      decrease in the excretion of fecal nitrogen being of sufficient magnitude to
      secure a lowered excretion of both the bacterial and the non-bacterial nitrogen.
      6. A decrease in the quantity of bacteria excreted daily. 7. An increase in the
      percentage of total nitrogen appearing as bacterial nitrogen. 8. A lower
      creatinine coefficient. 9. A more economical utilization of the protein
      constituents of the diet. 10. The general conclusion to be reached as the result
      of this experiment is to the effect that the drinking of a large amount of water
      with meals was attended by many desirable and by no undesirable features.

PMID- 19867335
TI  - THE QUANTITATIVE CHANGES IN THE PROTEINS IN THE BLOOD PLASMA OF HORSES IN THE
      COURSE OF IMMUNIZATION.
AB  - Gravimetric determinations were recorded for the total and several individual
      proteins (in the sodium oxalate plasma) fractioned with ammonium sulphate and
      sodium chloride. At precipitation, the plasma salt mixture had been diluted to a
      final volume of ten times the amount of plasma employed. Coagulations were on
      aliquot portions of filtrates, and the individual protein constituents (except
      serumalbumin) were calculated by difference. The eleven horses had been subjected
      to simultaneous immunization against diphtheria and tetanus toxins, each horse
      being subsequently continued on the toxin to which it responded best. Test
      bleedings of about 500 cubic centimeters only were made until maximum antitoxic
      potency (with almost coincident greatest variation See PDF for Structure in the
      contents of the several proteins) had been attained; routine bleedings of four to
      ten liters for antitoxin production were then instituted. The two refractory, one
      medium and the eight horses yielding a highly potent antitoxic plasma, all showed
      an increase of from 40 to 114 per cent. in the total serumglobulin. For the
      refractory animals, this increase was 59.3 and 87.9 per cents. In one refractory
      and in one high horse, the serumglobulin maximum preceded the highest
      concentration in antitoxin. In seven of the horses, the greatest increase in the
      total serumglobulin was coincident with the maximum antitoxic potency. The
      serumglobulin increase, however, tended relatively to precede that of the
      antitoxin. In the two other horses, both maxima also were observed together; no
      "intermediate" bleedings were made in these two instances. The greatest absolute
      increase in the serumglobulin was observed in the most potent plasma obtained in
      the series; the second place, however, went to a refractory horse. Subsequent to
      the maxima, the serumglobulin content was maintained at high concentration, in
      spite of repeated bleedings; it then only roughly paralleled the antitoxic
      variations in the plasma of the individual animals. At dilutions of the plasma in
      the precipitated mixtures of 1:15, 1:5 and 1:10, the ammonium sulphate
      "euglobulin" fraction amounted to about 60 to 70, 20 to 24 and 10 to 15 per
      cents., respectively, of the total serumglobulin in both the normal and the
      antitoxic plasma. In an 850 unit plasma, an increase in the "euglobulin" over the
      normal percentage was observed, but the high content of protein in this plasma
      probably influenced the precipitation limits. The influence of the protein
      concentration is indicated by the different percentages for the "euglobulin"
      obtained for the three dilutions of 1:15, 1:5 and 1:10. The "euglobulin" then was
      not increased to a greater extent than the "pseudoglobulin" as the result of
      immunization, as has at times been maintained. See PDF for Structure The
      "euglobulin" precipitated by saturating the plasma with sodium chloride (at
      ultimate dilution of the plasma 1:10) was much greater in normal plasma than the
      ammonium sulphate "euglobulin" at the same dilution. There was a tendency in
      early immunization for this sodium chloride "euglobulin" to increase along with
      the total serumglobulin; it rapidly diminished, however, until at the height of
      immunization and maximum serumglobulin concentration, it may have reached less
      than half the normal absolute amount. The serum albumin was diminished a third to
      a half the normal along with the serumglobulin increase. Subsequent to the anti-
      See PDF for Structure toxic and serumglobulin maxima, figures as low as a fifth
      of the original serumalbumin content have been noted. It is suggested that this
      diminution of the sodium chloride "euglobulin" and the serumalbumin is a
      physiological compensation for the greater viscosity of the plasma because of the
      increase in the more soluble serumglobulins. No characteristic alteration in the
      fibrinogen of the plasma was observed during immunization. Individual variations
      up to 0.5 gram per 100 cubic centimeters of plasma have been recorded. The
      influence of repeated bleedings does not essentially influence the protein
      changes induced by immunization. These remarkable regenerative processes are
      worthy of note. The results of our investigation indicate that in "forced"
      immunization, the same characteristic quantitative changes can occur in the blood
      proteins of both refractory horses and those yielding a highly potent antitoxic
      plasma. We cannot conclude, however, that the serumglobulin increase does not
      represent an accumulation of antitoxin, at least in part; it is possible that
      other antibodies may be formed either prior to or along with the specific
      antitoxin and that these may constitute a portion of the increase in the more
      soluble serumglobulin with which protein such substances are associated.

PMID- 19867336
TI  - THE CUTANEOUS TRICHOPHYTIN REACTION.
AB  - There exists a far-reaching analogy between the cutaneous trichophytin reaction
      and the cutaneous tuberculin reaction. Both indicate that the organism is the
      seat of a definite infection or that it has passed through such an infection.
      Both may persist for a long time after the active disease has come to rest,
      indicating that the infection has left the organism in a state of altered
      reactivity-allergy. Under certain conditions both may be of diagnostic value, but
      since the reaction persists for a long time after the infection has passed, the
      negative reaction may be of greater value, excluding the existence of a specific
      infection. The analogy of the trichophytin reaction with the tuberculin reaction
      is not only limited to the obvious clinical manifestations, but, as in the
      tuberculin reaction, it can be shown that with uniform concentration of antibody,
      the intensity of the reaction is dependent on the concentration of the
      trichophytin. A tentative explanation of the halo formation is offered, based on
      a rapidly renewed formation of antibody stimulated probably by the entrance of a
      small amount of allergen into the general circulation.

PMID- 19867337
TI  - LATENT LIFE OF ARTERIES.
AB  - When a segment of artery, killed by heat, formalin or glycerin is transplanted,
      it undergoes a rapid degeneration. Its muscle fibers disappear while the tissue
      of the host reacts by building a new wall of connective tissue. When the
      transplanted vessel has been preserved in a condition of latent life, no
      degeneration of the wall occurs, or the wall undergoes only partial degeneration.
      The muscle fibers can keep their normal appearance, even for a long time after
      the operation. It is, therefore, demonstrated that arteries can be preserved
      outside of the body in a condition of unmanifested actual life. The best method
      of preservation consists of placing the vessels, immersed in vaselin, in an ice
      box, the temperature of which is slightly above the freezing point. From a
      surgical standpoint, the transplantation of preserved vessels can be used with
      some safety. When the arteries were kept in defibrinated blood or vaselin and in
      cold storage, the proportion of positive results was 75 and 80 per cent., and
      this can probably be increased.

PMID- 19867338
TI  - STUDIES IN EDEMA : VII. THE INFLUENCE OF NEPHRECTOMY AND OTHER SURGICAL
      OPERATIONS AND OF THE LESIONS PRODUCED BY URANIUM NITRATE UPON ABSORPTION FROM
      THE PERITONEAL CAVITY.
AB  - 1. In the experiments recorded in this paper the influence of the osmotic
      pressure of the blood upon absorption of fluid from the peritoneal cavity becomes
      apparent. Nephrectomy, removal of the adrenals, and other operations increase the
      osmotic pressure of the blood and increase the absorption of fluid from the
      peritoneal cavity. On the other hand, ether narcosis, at the period at which we
      tested its influence, causes neither an increase of osmotic pressure of the blood
      nor an increase in the absorption of fluid from the peritoneal cavity. 2. The
      increased osmotic pressure and increased absorption of fluid in nephrectomized
      animals is to a great extent not a specific effect of the removal of the kidneys,
      but approximately the same conditions can be observed after incisions of the skin
      and muscles. 3. After poisoning with uranium nitrate and in cases of peritonitis,
      complicating factors come into play, and under such conditions the absorption
      from the peritoneal cavity is not increased, notwithstanding the higher osmotic
      pressure of the blood. 4. In conditions in which the osmotic pressure of the
      blood is very high before the injection of sodium chloride solution into the
      peritoneal cavity (nephrectomized rabbits or rabbits injected with uranium
      nitrate three days previously), adrenalin causes no increase, or only a very
      slight one, in the absorption of peritoneal fluid. On the other hand, one day
      after the injection of uranium nitrate the osmotic pressure of the blood is only
      slightly increased before the injection of the sodium chloride solution into the
      peritoneal cavity, and here adrenalin causes a marked increase in absorption of
      fluid from the peritoneal cavity. 5. In animals injected with uranium nitrate the
      retention of sodium chloride and other osmotically active substances in the blood
      is not entirely due to interference with the functions of the kidney. This
      retention may be explained either by an inability of the tissues to bind the
      sodium chloride and other osmotically active substances or to a diminished
      permeability of the blood vessels for such substances. 6. While in
      nephrectornized animals the elimination of sodium chloride from the peritoneal
      cavity and also from the blood is increased, in animals injected with uranium
      nitrate such an elimination is diminished. This increase in the sodium chloride
      content of the peritoneal fluid in animals treated with uranium nitrate is
      accompanied by a decrease in the diffusion of other osmotically active substances
      into the peritoneal cavity. 7. While in nephrectomized animals and in animals
      injected with uranium nitrate one day previously, adrenalin causes a diminution
      of the fluid retained in the blood-vessels similar to the diminution noted in
      normal animals, adrenalin no longer exerts such an effect at a later stage of the
      uranium nitrate poisoning. At this period after the administration of uranium
      nitrate, the retention of fluid in the blood vessels is apparently equal in
      experiments with and without the injection of adrenalin, and following the
      absorption of fluid from the peritoneal cavity, the retention of fluid in the
      blood vessels in the uranium nitrate animals is increased comparatively to a
      greater extent than in normal animals. 8. Our experiments show a marked
      difference in the distribution of fluid and of osmotically active substances in
      nephrectomized animals and in animals injected with uranium nitrate. This
      difference may explain the much greater liability to the development of edema in
      animals injected with uranium nitrate.

PMID- 19867339
TI  - STUDIES IN EDEMA : VIII. THE INFLUENCE OF CAFFEINE ON ABSORPTION FROM THE
      PERITONEAL CAVITY AND THE INFLUENCE OF DIURESIS ON EDEMA.
AB  - I. In normal animals the injection of caffeine slightly diminishes the absorption
      of fluid from the peritoneal cavity, in spite of the fact that the amount of
      fluid and sodium chloride eliminated through the kidneys is markedly increased.
      The lessened absorption of fluid is due to a slight lowering of the osmotic
      pressure of the blood. II. In nephrectomized animals caffeine increases the
      absorption of fluid from the peritoneal cavity; the increase in absorption is
      greater in nephrectomized animals which received caffeine than in nephrectomized
      animals which did not receive this substance, and it is due to additive increase
      in the osmotic pressure of the blood. In a similar manner, caffeine increases the
      absorption of fluid from the peritoneal cavity in animals in which, instead of
      nephrectomy, other operations, not directly affecting the kidneys, had been
      performed. In this case also the increase in absorption is presumably preceded by
      and due to an increase in the osmotic pressure of the blood. III. In animals
      injected with uranium nitrate three days previously, caffeine diminishes the
      absorption of fluid from the peritoneal cavity, notwithstanding the high osmotic
      pressure of the blood which we observe in such animals. This agrees with the
      results of our previous experiments in which we found that in animals injected
      with uranium nitrate the absorption of fluid is not increased in spite of the
      rise of the osmotic pressure of the blood. IV. At the time of the conclusion of
      the absorption experiments, the amount of fluid retained in the vessels was found
      to be diminished in each series in which caffeine was used. Only in certain cases
      can this be due to the increased amount of fluid leaving the blood vessels
      through the kidneys; in other cases it can only be due to a movement of water
      from the blood vessels into the tissues caused by the injection of caffeine. V.
      In normal animals, in nephrectomized animals and in animals in which an operation
      not directly affecting the kidneys had been performed, caffeine causes an
      absolute and relative increase in the elimination of sodium chloride from the
      peritoneal fluid, as a result of which the remaining peritoneal fluid shows a
      lessened content of sodium chloride. Caffeine causes also a decrease in the
      sodium chloride content of the blood. We see, therefore, that under the influence
      of caffeine a greater amount of sodium chloride is eliminated from the body
      fluids into the tissues or through the kidneys. The factors which cause the
      sodium chloride to leave the body fluids are probably primarily responsible for
      the diuresis which takes place after administration of caffeine. In the case of
      caffeine and other similar substances the diuresis is, therefore, in all
      probability not due primarily to a specific action of the kidney, but to
      conditions which affect the distribution of sodium chloride in the body. VI. The
      distribution coefficient of other osmotically active substances differs from that
      of sodium chloride. These other substances have a tendency to move into the body
      fluids in increased quantities under the influence of caffeine. VII. Summarizing
      all experiments in which we studied the absorption from the peritoneal cavity, we
      may state that changes in the osmotic pressure of the blood represent the
      principal factor in explaining the variations in the rate of absorption of fluid
      from the peritoneal cavity. VIII. There exists no direct relation between an
      increase in the rate of absorption of fluid from the peritoneal cavity and an
      increase in the amount of urine secreted. If it should be found that even at a
      period following the injection of caffeine, later than that at which we have
      studied the absorption, a rise of the osmotic pressure of the blood does not
      appear, then we may state that the diminution in the amount of edema in the body
      cavities resulting from the administration of caffeine is entirely due to an
      inhibition of the production of edema and not to an increased absorption of fluid
      from the serous body cavities.

PMID- 19867340
TI  - OBSERVATIONS ON THE ORIGIN, DISTRIBUTION AND SIGNIFICANCE OF FUCHSIN BODIES, WITH
      SPECIAL STAINING TECHNIQUE.
AB  - IN SUMMARIZING THE RESULTS OF THIS WORK I FEEL JUSTIFIED IN DRAWING THE FOLLOWING
      CONCLUSIONS: 1. The fuchsin body represents a type of body subject to wide
      variations in morphology and in staining reaction. 2. Though more frequently
      associated with plasma cells than with any other cell type, these bodies may and
      do occur in a great variety of cells. 3. Further, certain sections show
      unmistakable fuchsin bodies within blood vessels; some of these bodies are true
      hyaline thrombi, while others are due to autolytic changes in the red blood
      corpuscles. 4. Fuchsin bodies are most numerous in granulation tissue and
      lymphoid areas. In the former, they follow closely the distribution of
      capillaries and show a parallel with the changes in the extra- and intravascular
      red blood corpuscles. 5. The number and type of fuchsin bodies in tissues can be
      influenced by methods of fixation, the number of typical bodies being inversely
      proportional to the rapidity and degree of fixation of the red blood cells. 6.
      The type of body found after the best fixation is not, as a rule, what is
      considered the typical form, but an irregular fragmentary type or the
      fuchsinophilic granular form. 7. The identity in staining reaction, the constant
      association with changes in red blood corpuscles, the relation to distribution of
      capillaries in granulation tissues, the occurrence in hemorrhagic lesions
      associated with pigment, the intravascular occurrence, and, finally, the close
      relation to pigment deposits, all indicate conclusively that fuchsin bodies arise
      from red blood corpuscles. 8. No theory of origin from plasma cells, or other
      granular cells, offers an adequate explanation for the origin of fuchsin bodies,
      nor can any theory prove adequate which does not take into account the red blood
      corpuscles. 9. The peculiar association of plasma cells with fuchsin bodies and
      hemosiderin seems explainable on the assumption that the plasma cell in such
      instances is the active factor in a metabolic process, the fuchsin body
      representing a stage in the metabolism of hemoglobin by an intracellular enzyme,
      and hemosiderin, one of the products of the process.

PMID- 19867341
TI  - A STUDY OF AN EXTREMELY PURE PREPARATION OF RICIN.
AB  - 1. By following the method of Osborne, Mendel and Harris, we can obtain an
      extremely potent toxin from the castor bean. 2. It would appear, as a result of
      testing this preparation at the end of two and a half years, that the
      agglutinating function and the toxic function are two distinct properties. 3.
      This result is also borne out by the behavior under the electric current; either
      we are dealing with two different substances or else with a single substance with
      two distinct toxiphore groups, one of which is stable and the other labile.

PMID- 19867342
TI  - NEUROCYTOMA OR NEUROBLASTOMA, A KIND OF TUMOR NOT GENERALLY RECOGNIZED.

PMID- 19867343
TI  - SUBCUTANEOUS REACTION OF RABBITS TO HORSE SERUM.
AB  - 1. Anaphylaxis or allergy of rabbits against horse serum can be proved by
      subcutaneous test. 2. The test is best made in the following way. The skin of the
      animal, preferably of the abdomen or flank, is shaved. (This should be done a few
      hours before the injection.) The injection is made by means of a small hypodermic
      syringe and intradermally. An effort was made not to inject the serum under the
      skin. Those injections were considered most favorable by which the serum remained
      as a small bleb in the skin proper. Undiluted horse serum was used for most of
      the experiments. The amount injected varied from 0.0I cubic centimeter to I cubic
      centimeter. The reaction seemed as definite after 0.0I cubic centimeter as after
      a larger quantity. See PDF for Structure 3. The specific reaction appears in from
      twelve to twenty-four hours after the test is made and reaches its maximum in
      from twenty-four to thirty-six hours. It consists of a local swelling extending
      from 0.5 to 2 centimeters from the point of inoculation. The skin involved in the
      raised area is usually red and hotter than the surrounding skin. Macroscopically
      and microscopically the reacting area has the appearance of a local acute
      inflammation. 4. The altered reactivity (allergy) or hyper-susceptibility
      (anaphylaxis) sets in usually in from ten to fifteen days after the first
      injection of horse serum, and lasts at least three months. Individual rabbits
      show marked variation from the average time of the development of anaphylaxis. 5.
      The appearance of precipitines against horse serum in the blood of rabbits
      appears nearly synchronously with the allergic condition. 6. After large
      injections of serum the allergic rabbits still react subcutaneously. A
      suppression of allergy which would correspond to the so-called anti-anaphylaxis
      could not be proved. 7. Also in regard to the offspring of injected rabbits the
      subcutaneous test was not positive. The young of these rabbits did not develop a
      more active allergy than the young of normal rabbits. 8. Neither the injection of
      considerable quantities of horse serum nor the development of a marked local
      reaction in the skin after intradermal inoculations of horse serum in a
      sensitized rabbit is accompanied or followed by greater variations in the number
      or types of leucocytes in the circulating blood than is found in control animals.

PMID- 19867345
TI  - ANOTHER POINT OF RESEMBLANCE BETWEEN ANAPHYLACTIC INTOXICATION AND POISONING WITH
      WITTE'S PEPTON.

PMID- 19867344
TI  - EFFECT OF VARIOUS AGENTS ON THE BLOOD FLOW THROUGH THE CORONARY ARTERIES AND
      VEINS.
AB  - The results obtained show that adrenalin, transfusion with salt solution, and the
      inhalation of tobacco smoke caused an increased circulation in the coronary
      vessels. Amyl nitrite and nitroglycerin produce the opposite effect. Digitalis,
      strophanthus, caffeine, and theobromine give no change in the velocity of
      circulation. We can conclude from the results that the blood pressure is the main
      element which influences coronary circulation, while the other factors play only
      a minor part in its variations.

PMID- 19867346
TI  - STUDIES ON IMMUNITY IN CANCERS OF THE WHITE RAT.

PMID- 19867347
TI  - THE RELATION OF FATTY DEGENERATION TO THE OXIDATION OF PURINES BY LIVER CELLS.
AB  - These experiments show that it is possible to cause, by the proper use of
      hydrazine and phosphorus, a very high degree of fatty change in the liver with a
      minimum of necrosis, involving alike both peripheral and central portions of the
      lobule and thus eliminating the " factor of safety" or residual normal cells.
      Nevertheless, it is found that such fatty liver tissue has not lost in the least
      its power to oxidize uric acid when acting upon it in vitro with abundant air
      supply, nor is the power to oxidize xanthine to uric acid noticeably diminished.
      Since these two enzymes, and especially the uricolytic enzyme, are about the last
      to appear in the development of the animal kingdom and also of the individual
      mammal, it is to be expected that they will be among the first of the enzymes to
      be destroyed by injurious agencies, but evidently they are not affected by
      conditions that lead to the highest degree of fatty metamorphosis of the
      cytoplasm of the hepatic cells. While these experiments merely prove that extreme
      fatty degeneration does not destroy or appreciably diminish the power of liver
      cells to oxidize uric acid and xanthine in vitro, yet they suggest that in
      general fatty degeneration is probably not essentially incompatible with a high
      degree of metabolic activity by the affected cells. It is possible that in the
      living tissue functional activity may be decreased secondarily by fatty
      metamorphosis, as, for example, by the enlarged fatty cells compressing the
      capillaries and reducing circulatory activity, or by modification of diffusion
      through the cell by the fat deposits, independent of any deleterious influence
      upon the cellular enzymes themselves. Other experiments will be required to
      determine whether steatogenic poisons leave intrahepatic enzymes other than the
      uricase equally unaffected, but as it has already been shown by Jacoby that the
      autolytic enzymes and aldehydase in the liver cells are not destroyed by
      phosphorus poisoning, and Abderhalden and Schittenhelm* found that peptids are
      hydrolyzed fully as rapidly by phosphorus livers as by normal livers, it seems
      probable that extreme fatty metamorphosis is not associated with any serious
      injury to the enzymes by which the liver cells perform their metabolic functions,
      with the possible exception of those enzymes concerned with the metabolism of
      fats.

PMID- 19867348
TI  - EXPERIMENTAL YAWS IN THE MONKEY AND RABBIT.
AB  - 1. Rabbits can be infected in the testicle with the spirochetae of yaws as well
      as with those of syphilis and the infection can be continued through successive
      generations in pure culture. 2. The infection shows itself by enlargement of the
      testicle and the presence of a nodule varying in size from that of a pea to that
      of an olive. The infection consists in a necrosis of the tubules, an infiltration
      of round cells and the new formation of an edematous connective tissue. 3. The
      complement fixation reaction occurs in rabbits infected with the spirochetae of
      yaws as well as in those infected with the spirochetae of syphilis. 4. This
      lesion makes possible the investigation of the problems of cultivation, of
      immunity and of treatment.

PMID- 19867349
TI  - CHANGES IN THE HEMOSIDERIN CONTENT OF THE RABBIT'S LIVER DURING AUTOLYSIS.
AB  - 1. Hemosiderin may be produced outside of the animal body and is increased in the
      liver of rabbits, during autolysis, for a period of from twenty-four to forty
      eight hours. 2. Post-mortem hemosiderin formation is most marked in parts of
      livers exposed to air, and hemosiderin is, apparently, an oxidation product of
      hemoglobin due to enzyme action. 3. Hemosiderin is derived from hemoglobin
      directly and not from hematin as an intermediate product. 4. The later stages of
      autolytic changes show that the acid products of proteid autolysis, especially
      the phosphorus acids, are capable of producing a cleavage of hemosiderin and
      uniting with the iron to form a new series of products which react
      microchemically for both phosphorus and iron. In such cleavage, pigments
      analogous to the bile pigments are formed. 5. The relationship observed between
      hemosiderin and hematoidin is such as would indicate that hematoidin is the
      pigment matter of hemosiderin. 6. Further, it seems probable that the vital cycle
      of hemoglobin metabolism in the liver is largely intranuclear; the hemoglobin is
      converted into hemosiderin either within the nucleus or cell protoplasm; the iron
      of the hemosiderin is bound by an acid radicle of the nucleo-proteid, and the
      hematoidin is excreted as bile pigment.

PMID- 19867350
TI  - THE EFFECT OF VAGUS SECTION UPON ANAPHYLAXIS IN GUINEA PIGS : SECOND
      COMMUNICATION.
AB  - Depriving the bronchial muscles of one side of the lungs of their motor
      innervation does not interfere with sensitization nor the production of the
      typical anaphylactic lung. There is, therefore, direct sensitization of the
      muscle substance. Complete degeneration of the vagus nerve, after sensitization
      has occurred, interferes in no appreciable way with the course of immediate
      anaphylaxis. Partial degeneration of the vagus nerve, so that the bronchodilator
      fibers are still physiologically active, after sensitization has taken place,
      exerts no effect on the symptoms and lung picture of immediate anaphylaxis (very
      acute anaphylaxis with death after some minutes). No definite evidence was
      obtained regarding the function of the motor nerve endings in the bronchial
      muscles in anaphylaxis. The two sides of the lungs in immediate anaphylaxis may
      occasionally be unequal; when this occurs, the left side, especially the lower
      lobe, is usually fuller than the right side.

PMID- 19867351
TI  - THE CULTIVATION OF THE LEPROSY BACILLUS AND THE EXPERIMENTAL PRODUCTION OF
      LEPROSY IN THE JAPANESE DANCING MOUSE.
AB  - Pure cultures of an acid-fast bacillus were cultivated upon special media from
      the human tissues in four cases of leprosy. The nature of the growth,
      morphological characters and tinctorial properties do not differ for any of the
      cultures and correspond closely to the bacilli in the human leprous tubercles.
      That the bacillus of leprosy will multiply and continue to do so indefinitely
      outside of the animal body was first demonstrated by Clegg who cultivated an acid
      fast organism from leprosy tissue in the presence of ameba and their symbiotics.
      Not only have I been able to confirm Clegg's work, but in addition I have
      succeeded in growing the bacillus in pure culture and in reproducing the disease
      in the Japanese dancing mouse, thereby establishing its identity. This species of
      animal acquires the infection in four to six weeks after intraperitoneal or
      subcutaneous inoculation with either emulsions of fresh leprous tissue or the
      pure cultures of B. leprae. Comparatively few bacilli are necessary to infect the
      mouse; and the mode of inoculation does not seem to make any appreciable
      difference in respect to the nature and time of development of the lesion. The
      experimental lesions are proliferative in character and identical with those in
      the human subject. Macroscopically they appear as glistening, white nodules
      which, in the early stages of development, resemble miliary tubercles. In my
      experience neither the cultures nor the bacilli directly from the human tissues
      have shown any evidence of multiplication or given rise to lesions when injected
      into the ordinary laboratory animals such as guinea pigs, rabbits, gray and white
      mice and rats, although repeated attempts have been made to infect these animals.
      B. leprae will not only multiply but it will colonize on a plain agar medium
      seeded with a pure culture of encysted ameba (Plate LVIII, Fig. 5), and upon an
      agar or banana medium prepared with a I per cent. solution of cystein and
      tryptophane. Colonization occurs in the form of glistening, white colonies, one
      to two millimeters in diameter, in from one to two months incubation. The bacilli
      in cultures are at all times acid-fast and differ only in morphology from those
      of the tissues in that they exhibit a greater variation in the distribution of
      the chromatin and are longer and more distinctly curved. To prove that the
      cultures obtained from the human tissues of these four cases are leprosy bacilli
      and not some other acid-fast species, the following facts are offered: (1) the
      growth features are distinctive and multiplication takes place only under special
      conditions of temperature and medium; (2) the complete correspondence in
      tinctorial properties and similarity in morphology to those in the tissues; (3)
      the failure to multiply or produce lesions in the common laboratory animals; and
      (4) the growth of the bacilli and the production of typical leprous lesions in
      the Japanese dancing mouse. The successful cultivation of B. leprae and the fact
      that the cultures retain pathogenic properties are of commanding importance in
      respect to a possible production of an artificial immune serum for combating the
      infection in man. Work along this interesting line is already in progress in our
      laboratories.

PMID- 19867352
TI  - INTRACELLULAR PROTEOLYTIC ENZYMES OF LIVER.

PMID- 19867353
TI  - THE CELL CHANGES IN AMAUROTIC FAMILY IDIOCY.

PMID- 19867354
TI  - A TRANSMISSIBLE AVIAN NEOPLASM. (SARCOMA OF THE COMMON FOWL.).
AB  - In this paper is reported the first avian tumor that has proved transplantable to
      other individuals. It is a spindle-celled sarcoma of the hen, which thus far has
      been propagated into its fourth tumor generation. This was accomplished by the
      use of fowls of pure blood from the small, intimately related stock in which the
      growth occurred. Market-bought fowls of similar variety have shown themselves
      insusceptible, as have fowls of mixed breed, pigeons and guinea-pigs. The
      percentage of successful transplantations has been small, but in the individuals
      developing a tumor its growth has been fairly rapid. Young chickens are more
      susceptible than adults. The reinoculation of negative fowls has never resulted
      in a growth. Throughout, the sarcoma has remained true to type. It is
      infiltrative and destructive. Metastasis has been observed once (to the heart).
      Experiments to determine whether the growth may be transmitted by cell-fragments
      have not yet been made. Repeated bacteriological examinations have yielded
      negative results. In its general behavior, so far as tested, this avian tumor
      closely resembles the typical mammalian neoplasms that are transplantable.

PMID- 19867355
TI  - CONCERNING COMPENSATORY HYPERPLASIA OF THE INTIMA.
AB  - We agree with Jores and others that not one but many factors may be at work
      leading to intimal hyperplasia. Among these factors may be mentioned infection,
      bacterial toxins, organic poisons, inflammation and increased arterial tension.
      The theory of Thoma that the connective tissue developed in the intima is
      compensatory cannot be sustained. From the evidence which we have at hand it is
      not possible to state that the proliferative changes in the intima are uniformly
      secondary to the weakening of the media. Common influences may act simultaneously
      upon the media and the intima. Progressive medial degeneration of the peripheral
      arteries (Moenckeberg's sclerosis) is the result of muscle fatigue coupled with
      nutritional disturbance.

PMID- 19867356
TI  - OBSERVATIONS UPON THE NOGUCHI MODIFICATION OF THE WASSERMANN COMPLEMENT FIXATION
      TEST IN THE DIAGNOSIS OF LUES IN THE MILITARY SERVICE.
AB  - In the vast majority of cases examined in this laboratory the result of the
      Wassermann test was simply confirmatory of the clinical findings, but there were
      numerous suspicious cases, or cases in which symptoms were present and the
      patient denied a specific history, in which the test was of the greatest value,
      and it is in such instances, perhaps, that it may be regarded as "the court of
      last resort " in arriving at a conclusion regarding the nature of the condition
      present. Certainly if there is any value in experience and statistics, we are
      justified in regarding this test as the most valuable means we possess of
      diagnosing lues, and our experience with the Noguchi modification of the test has
      justified all that has been claimed for that method. We believe that our results
      have proven that by the use of the complement fixation test in the military
      service it is possible to prevent the enlistment of men suffering from latent
      lues who would otherwise be enlisted; to control specific treatment by using it
      as an index of the efficiency of such treatment; to clear up the diagnosis of
      obscure or suspicious cases; and to enable the surgeon to avoid mistakes in
      discharges for disability in cases suspected of this disease. Owing to the
      facility with which clinical observations can be made in armies, and the control
      that is possible of tested individuals, it is to be hoped that the Noguchi
      modification of the complement fixation test will be more widely used than it has
      been in the military services, for which we believe it is especially adapted. So
      far as we are aware the Medical Department of our army is the first to adopt this
      test as a routine diagnostic procedure and to apply it in the case of applicants
      for enlistment.

PMID- 19867357
TI  - THE DISTRIBUTION OF FAT IN THE LIVER.
AB  - 1. Nearly all livers at autopsy contain fat which is histologically demonstrable.
      2. Fatty substances in the liver appear chiefly in two forms, as small granules
      and as globules of various sizes. 3. We suppose that granules indicate the
      (protoplasmic) change commonly spoken of as fatty degeneration, and that globules
      of small size are excess of fat, stored up by reason of some pathological change
      which may be merely temporary. 4. Fat is oftenest central, least often in the mid
      zone. 5. A heavy deposit of fat is compatible with a competent liver. 6. Intense
      fattiness, generally globular, occurs with intoxications of bacterial and
      chemical nature, as well as in cases where a complex toxin is manufactured by the
      body-cells. 7. Granular fat occurs oftener than globular: it affects most often
      the central zone; globular affects most often the peripheral. 8. " Accidental "
      masses of globular fat are found at times, and appear to follow no rule of
      position: these are comparable to lipomata, which are evidently the result of a
      pathological process. 9. We found no deposit of fat characteristic of uremia. 10
      We know of no analysis of the liver fats in the granular and globular states
      respectively: it seems to have been taken for granted that the deposits were one
      and the same. To determine the relationship, if any, between these two forms
      should be the basis of investigation.

PMID- 19867359
TI  - General introduction.

PMID- 19867358
TI  - OBSERVATIONS UPON THE ACTION OF SALTS ON THE CATALASE OF THE BLOOD IN RABBITS.
AB  - Bicarbonate of soda fed in varying quantities over a period of months has no
      direct effect upon the catalytic activity of the blood. When fed to rabbits, it
      invariably causes a slight albuminuria and occasional casts. The kidneys of
      pregnant animals, especially in the later stages of pregnancy, seem to be more
      susceptible to this salt, and in some instances there may be complete suppression
      of urine followed by death. In these cases there is a decline in the catalytic
      activity of the blood similar to that observed in cases of acute nephritis,
      following the administration of uranium nitrate. The subcutaneous injection of
      salts is impracticable on account of the slow absorption. In intravenous
      injections it is important to make observations during the injection and at short
      intervals after the injection has been discontinued, since there is a rapid
      compensation on the part of the organism with a return of the normal catalytic
      activity of the blood. The simple diluting effect brought about by the injection
      of distilled water into the circulation manifests itself as a slight transitory
      decrease in the catalytic activity of the blood. This must be taken into
      consideration when estimating the effect of the injection of solutions of salt
      upon the catalase of the blood. Salts, such as sodium chloride, sodium
      bicarbonate, sodium sulphate and potassium iodide, acids, such as sulphuric, and
      alkalies, such as sodium hydrate, cause a definite decrease in the catalytic
      activity of the blood. This decrease varies directly with the concentration of
      the salt. The organism compensates rapidly and brings about a return to the
      normal activity. This compensation becomes less and less complete as larger
      quantities or repeated infusions are made. For example, twenty cubic centimeters
      of a five per cent. bicarbonate of soda solution causes a marked fall in the
      catalytic action of the blood. This is rapidly recovered from in from one to five
      minutes, and then a much more marked fall in the activity, requiring a longer
      time for compensation, occurs after the injection of six cubic centimeters of the
      same solution. It is of interest to note that sodium sulphate and potassium
      iodide, which have been shown to accelerate the catalytic activity of liver
      extract in the test-tube, have an inhibiting effect on the action of the blood
      when injected intravenously. This is only another instance of the dangers to be
      encountered from the immediate application of test-tube experiments to the living
      organism. The inhalation of carbon dioxide gas, even until convulsions are
      manifested, is without effect on the catalytic activity of the blood. On the
      other hand, there is a definite decline in this activity following the
      administration of illuminating gas. In this respect our results are directly at
      variance with those of Jolles.

PMID- 19867360
TI  - Complement-derived leukotactic factors in pathological fluids.
AB  - Leukotactic factors derived from the complement sequence consist of C5-related
      products, including the small cleavage product and the higher molecular weight
      complex (C567). A leukotactically active cleavage product (of low molecular
      weight) has also been described. The C5-related factors have been found in two
      conditions: soluble tissue extracts of immunologic vasculitis and in synovial
      fluids from patients with rheumatoid arthritis. The C3-related product has been
      found in synovial fluids from patients with inflammatory, nonrheumatoid arthritis
      and in extracts of experimentally infarcted myocardium. The presence of these
      factors may be causally related to the acute inflammatory nature of the cellular
      exudates.

PMID- 19867361
TI  - Interaction of cells with immune complexes: adherence, release of constituents,
      and tissue injury.
AB  - Neutrophils are essential mediators of tissue damage in many forms of immune
      complex-induced injury. In vitro, they have been shown to release some of their
      content of injurious constituents upon reaction with immune complexes (Fig. 10).
      If the complexes are distributed along a nonphagocytosable surface, degranulation
      to the exterior of the cell is observed. When the complexes were phagocytized,
      however, degranulation into the phagocytic vacuole, and some loss of enzymes into
      the surrounding medium, occurred. This may have resulted from a momentary opening
      of the vacuole to allow ingestion of additional particles, as was demonstrated
      with the electron microscope. This phenomenon was particularly noticeable when
      the particles were relatively large. Far more immune complex is required to
      induce release when in a phagocytosable form than when on a nonphagocytosable
      membrane. Neutrophils may be attracted to sites of immune complex deposition in
      many parts of the body (arteries, heart, skin, brain, kidney, joints) by
      complement-mediated processes. In some situations, e.g. in the joint fluid, they
      would encounter free immune complexes, phagocytose them, and release enzymes. In
      many others, in which immune complexes may be distributed along surfaces, such as
      in the glomerulus, adherence of neutrophils may also lead to release of injurious
      constituents (proteases, collagenase, elastase, permeability factors) capable of
      digesting and injuring the tissues.

PMID- 19867362
TI  - Immunological release of histamine and slow-reacting substance of anaphylaxis
      from human lung : I. Modulation by agents influencing cellular levels of cyclic
      3',5'-adenosine monophosphate.
AB  - The sensitization of human lung with atopic serum is both time and temperature
      dependent. Highly purified IgE myeloma protein is capable of blocking
      sensitization of human lung with atopic serum whereas myeloma proteins of the IgG
      subgroups are inactive. Drugs capable of increasing cellular levels of CAMP such
      as beta-adrenergic agents and methylxanthines inhibit the antigen-induced release
      of both histamine and SRS-A from human lung and these agents demonstrate
      synergism when used together. The beta-adrenergic blocking agent, propranolol,
      prevents epinephrine-induced inhibition of the immunologic release of the
      mediators. Diethylcarbamazine also inhibits the antigen-induced release of
      histamine and SRS-A from human lung and a synergism between this drug and
      epinephrine is observed. Predominantly alpha-adrenergic stimulation achieved by
      combining propranolol with epinephrine or norepinephrine not only prevented the
      inhibitory activity of the sympathomimetic amines but also resulted in an
      enhanced release of histamine and SRS-A. These observations suggest that whereas
      increases in cellular levels of CAMP are inhibitory, decreases in cellular levels
      of CAMP enhance the antigen-induced release of the mediators.

PMID- 19867363
TI  - Mechanisms of lysosomal enzyme release from leukocytes exposed to immune
      complexes and other particles.
AB  - Human PMN release lysosomal enzymes (beta-glucuronidase, acid phosphatase) when
      exposed to immune complexes, but do not release cytoplasmic LDH. The cells remain
      viable, and failure of LDH to appear in supernatants is not due to selective
      absorption or inactivation. Release of enzymes is not due to platelet
      contamination and is only partially enhanced by fresh serum. The selective
      release of lysosomal enzymes after uptake of complexes resembles that induced by
      inert particles of zymosan, and can be distinguished from the concurrent release
      of all enzymes after cell death induced by membrane-lytic crystals of MSU. Uptake
      of complexes, zymosan, or MSU particles is accompanied by concomitant increases
      in C-1 oxidation of glucose. Although MSU-induced damage can be retarded by the
      presence of Tris buffer, immune complexes and zymosan selectively release
      lysosomal hydrolases in the presence or absence of Tris buffer. Agents which
      elevate the level, within cells, of cAMP (PGE(1), theophylline, 2-CA) and cAMP
      itself inhibit the selective extrusion of acid hydrolases from leukocytes without
      affecting the viability of cells. Leukocytes may respond to immune particles by
      regurgitating a portion of their lysosomal hydrolases during phagocytosis.

PMID- 19867364
TI  - Systemic lupus erythematosus: prototype of immune complex nephritis in man.
AB  - Serological studies, immunofluorescence studies, and immunochemical assays of
      glomerular eluates indicate that several antigen-antibody systems may be involved
      in the pathogenesis of the tissue lesions of SLE. The NDNA-anti-NDNA system
      appears to be operative in most patients with active SLE. In addition, antibodies
      to SDNA are found with considerable frequency in SLE sera and glomerular eluates.
      It is not known if these antibodies fix to NDNA which has been denatured after
      deposition in glomeruli or if SDNA-anti-DNA complexes are deposited initially.
      NDNA antigen has been demonstrated in both serum and glomerular deposits, and
      SDNA determinants have also been found in glomerular deposits. In addition, there
      is evidence that rheumatoid factor contributes to the immune complex deposition
      in certain patients either by fixing to preformed immune complexes or as part of
      an independent gamma-globulin-anti-gamma-globulin system. It is anticipated that
      the definition of these immune systems, and the assessment of their relative
      toxicity will provide insight into underlying etiologic factors as well as
      provide a sound basis for therapy in this form of glomerulonephritis.

PMID- 19867365
TI  - The role of streptococci in human glomerulonephritis.

PMID- 19867366
TI  - Fate of preformed immune complexes in rabbits and rhesus monkeys.
AB  - Preformed soluble immune complexes injected into rabbits or rhesus monkeys showed
      similar characteristics of disappearance from circulation. Complexes made with
      intact gammaG-antibodies and exceeding the Ag(2)Ab(2) lattice formation were
      rapidly removed by the hepatic RES. These complexes fixed complement effectively
      in vitro. Their hepatic uptake was not dependent upon circulating complement
      components, since their accumulation in the liver was unchanged in complement
      depleted rabbits. Similar antigen-antibody complexes made with reduced and
      alkylated gammaG-antibodies fixed complement ineffectively in vitro. These
      complexes possessed different disappearance characteristics and were not rapidly
      taken up by the liver, regardless of their degree of lattice formation. Both in
      vitro and in vivo studies failed to suggest any role for the immune adherence
      receptor on primate erythrocytes in the handling of circulating soluble immune
      complexes composed of BSA and gammaG-antibodies to this antigen.

PMID- 19867367
TI  - Immunologic injury of renal homografts.
AB  - Rejection of renal allografts in man and animals is most frequently induced by
      cell-mediated immunity, the morphologic hallmark of which is the infiltration of
      the graft by mononuclear cells. In some presensitized recipients rejection may be
      mediated by humoral transplantation antibodies, and this is characterized
      clinically by a rapid tempo of rejection and morphologically by accumulation of
      polymorphonuclear neutrophils and renal cortical necrosis. In recipients treated
      with immunosuppressive drugs, most renal allografts function well for over 1 yr.
      However, late deterioration is observed in many grafts. This may take the form of
      proliferative glomerulonephritis with accumulation of immunoglobulin and
      complement along glomerular basement membranes. This glomerular lesion of the
      graft may be of immunologic nature without being rejection. In many instances the
      glomerular lesion may be due to recurrence of the original disease of the
      recipient. In other instances it may represent a de novo immunologic process
      induced by the response to antigens shared by the graft and recipient as
      evidenced by animal experiments. The glomerular lesion in the graft may also be
      caused by humoral transplantation antibodies. Therefore, the final outcome of the
      renal transplantation may to a great extent depend on the strength of
      transplantation antibody response, being more favorable for low than high
      responders.

PMID- 19867368
TI  - Studies on chronic membranoproliferative glomerulonephritis with
      hypocomplementemia.
AB  - CMPGN with hypocomplementemia appears to be one identifiable form of progressive
      and destructive glomerulonephritis, but whether this is a specific pathogenetic
      entity has not been proven. The clinical features of the "disease" include
      presentation with either asymptomatic proteinuria and hematuria, nephrotic
      syndrome, or gross hematuria and an acute nephritic syndrome. Morphologic studies
      reveal extensive mesangial cell proliferation and increased matrix with
      thickening of the glomerular capillary. Deposits of C3 and properdin uniformly
      are found predominantly in a peripheral lobular distribution by immunofluorescent
      microscopy; immunoglobulins are seen less consistently. These deposits are
      different from those seen in other glomerular diseases. Serum complement
      abnormalities have also been demonstrated: depression of C3t (and
      beta(1)C/beta(1)A) with relatively normal earlier components, evidence for in
      vivo breakdown of C3 by labeled isotope studies and elevated alpha(2)D, presence
      of a serum inhibitor that inactivates guinea pig C3t and a pseudoglobulin lytic
      factor that in combination with a normal serum cofactor enzymatically cleaves C3
      to alpha(2)D and beta(1)A. The terminal complement inactivation and the uniform
      presence of properdin in these deposits suggesting an alternate pathway of immune
      injury must be balanced against immunopathologic observations which demonstrate
      glomerular deposits of immunoglobulins and earlier complement components. It is
      possible that both mechanisms may be operative in CMPGN.

PMID- 19867369
TI  - C1q PRECIPITINS IN THE SERA OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND
      OTHER HYPOCOMPLEMENTEMIC STATES: CHARACTERIZATION OF HIGH AND LOW MOLECULAR
      WEIGHT TYPES.
AB  - Precipitin reactions of C1q in gel diffusion proved useful in detecting unknown
      complexes containing gamma-globulin in the sera of patients with SLE. Using this
      method low molecular weight C1q reactants also have been detected in a number of
      sera from patients with SLE as well as other diseases. Both the circulating
      complexes and the unidentified low molecular weight reactants are associated with
      disease activity and in vivo complement depression. In some sera from patients
      with SLE, circulating complexes as detectable by C1q precipitation were closely
      associated with cryoprecipitins and an active nephritic process. Evidence is
      presented that both rheumatoid factors and C1q interact with circulating
      complexes in these patients and that the interaction is related to
      cryoprecipitation. The demonstration of the same rheumatoid factors in the
      cryoprecipitates and in the renal glomerular deposits suggests that rheumatoid
      factors have a special significance in the presence of circulating complexes.

PMID- 19867370
TI  - The value of immunofluorescence in the study of human renal disease.
AB  - Immunofluorescence is a useful technique in the study of human renal diseases,
      both from the point of view of elucidating pathogenic mechanisms and as a
      diagnostic tool. The finding of characteristic staining patterns for
      immunoglobulins and complement indicates that many forms of glomerulonephritis
      are immune complex diseases and that a few are due to anti-GBM antibodies. On the
      other hand, in lipoid nephrosis and toxemia of pregnancy, deposits of
      immunoglobulins and complement are generally absent, indicating that immunologic
      mechanisms are probably not responsible for these glomerular diseases. The
      finding of fibrin or other fibrinogen derivatives in glomeruli in toxemia of
      pregnancy and in certain forms of glomulonephritis supports the interpretation
      that these substances play a pathogenic role in certain glomerular diseases. The
      use of immunofluorescence has led to the recognition of two previously
      unrecognized renal diseases: nephropathy with mesangial IgA-IgG deposits
      (Berger), and a tubular disorder with deposits of immunoglobulins and complement
      along the basement membrane.

PMID- 19867371
TI  - Hemolytic assay of the ninth complement component: elevation and depletion in
      rheumatic diseases.
AB  - An effective molecule titration for the ninth component of complement in the
      biologic fluids of man was developed using EAC1-8 cells produced by treating
      EAC14 cells with a chromatographic fraction of human serum containing C2, C3, C5,
      C6, C7, and C8. Kinetic studies of the interaction of EAC1-8 with C9 indicated
      that this component was depleted from the fluid phase, and that the lytic
      reaction proceeded most rapidly at ionic strength 0.145, and at a temperature of
      37 degrees C. The mean value for C9 in normal serum was 52,000 +/-12,000
      units/ml. The mean serum C9 for patients with DJD, rheumatoid arthritis, or SLE
      without active renal disease was approximately twice the mean for normal
      individuals. Patients with SLE and active renal disease had a mean C9 value which
      fell within the normal range, but was significantly lower than in patients with
      SLE who did not have active renal disease. Two instances of absolutely subnormal
      C9 levels were observed in patients during attacks of florid SLE, including
      nephritis. Since the usual change in serum C9 in rheumatic diseases is a marked
      elevation, the occurrence of a subnormal value reflects circumstances in which
      depletion due to activation of the sequence exceeds the increases associated with
      the inflammatory response.

PMID- 19867372
TI  - Immunoreactants in rheumatoid synovial effusions.
AB  - Measurements were made of the IgG in synovial fluid which is synthesized by the
      intact rheumatoid synovium. In five rheumatoid subjects 12-24% of the IgG present
      in their synovial fluid was derived from local production. No evidence for local
      production was found in patients with degenerative arthritis or Reiter's
      syndrome. It was estimated that as much as 95 mg of IgG was produced by the
      synovium of a single knee joint daily. Rheumatoid inflammation is associated with
      the presence of large numbers of white blood cells, predominantly
      polymorphonuclear, in the articular cavity. Each day as many as one billion white
      cells enter the articular cavity to participate in this inflammatory response.
      Factors causing the directed migration of polymorphonuclear leukocytes were found
      in the majority of rheumatoid effusions studied. The chemotactic activity is, in
      large part, related to the fifth (C5) and sixth (C6) components of human
      complement. Physical-chemical techniques indicate that the activity is
      attributable to C 567 and C5a, a cleavage product of C5. In addition to the
      presence of preformed chemotactic factors, more than half of the rheumatoid
      fluids contain an enzyme capable of generating chemotactic activity from the
      fifth component (C5) of human complement. This information supports the concept
      that rheumatoid joint inflammation is an example of immune complex disease in
      which a significant proportion of the immunoreactants are derived from local
      production.

PMID- 19867373
TI  - OCCURRENCE OF gamma-GLOBULIN COMPLEXES IN SERUM AND JOINT FLUID OF RHEUMATOID
      ARTHRITIS PATIENTS: USE OF MONOCLONAL RHEUMATOID FACTORS AS REAGENTS FOR THEIR
      DEMONSTRATION.
AB  - gammaG globulin complexed in an unusual form has been demonstrated in the serum
      of many patients with rheumatoid arthritis. Such complexes have been detected and
      isolated principally through precipitation reactions with monoclonal gammaM
      rheumatoid factors. These monoclonal rheumatoid factors exhibited a greater
      sensitivity to react with small complexes or aggregates of gamma-globulin than
      polyclonal rheumatoid factor from rheumatoid arthritis sera or isolated C1q. The
      serum complexes consisted in large part of high molecular weight but acid
      dissociable 7S gammaG globulin molecules They however differed from the complexes
      in the joint fluid by not yielding precipitates with C1q and were not found in
      association with evidence of marked serum complement fixation or activation. A
      small number of systemic lupus erythematosus sera, primarily those forming
      cryoprecipitates, also gave reactions with monoclonal rheumatoid factor. Sera
      from patients with a variety of nonrheumatic diseases gave a low incidence of
      reactions. The exact nature of the complexes in the rheumatoid arthritis sera
      remains somewhat in doubt although gammaG rheumatoid factors appear partly
      involved.

PMID- 19867374
TI  - Immunohistologic studies of synoviocytes and synovial exudate cells.
AB  - Inclusions were demonstrated in normal polymorphonuclear cells incubated with
      rheumatoid factor-positive synovial fluid. These stained positively for IgG, IgM,
      and the beta(1)C component of complement. When normal polymorphonuclear cells
      were incubated with factor-negative rheumatoid fluid, inclusions were not
      obtained. However, after addition of IgM rheumatoid factor to such fluids,
      discrete inclusions were observed with similar staining properties. In a minority
      of nonrheumatoid fluids, inclusions were also obtained after addition of IgM
      rheumatoid factor. The phagocytosis of inclusions from synovial fluids after
      addition of IgM rheumatoid factor suggests the presence of aggregated IgG in
      these fluids. Immunofluorescent staining of phagocytic synovial lining cells,
      isolated from synovial tissue by trypsin digestion, demonstrated a diffuse
      staining pattern for IgG and the beta(1)C component of complement in cells from
      both seropositive and seronegative patients. In seropositive patients, discrete
      inclusions were also observed which stained positively for IgG, IgM, and
      beta(1)C. These findings provide evidence of in vivo phagocytosis of immune
      complexes from the synovial fluid.

PMID- 19867375
TI  - Properties of synovial cells in culture.
AB  - Derangements of synovial membranes and cartilage occur early in the course of
      rheumatoid arthritis. These important alterations of the joint tissues are
      probably the in vivo reflections of complicated inflammatory and immunological
      events. In our laboratory we have been interested in studying alterations of
      synovial lining cells in rheumatoid arthritis, most recently by the use of
      serially propagated cultures of these cells. The cellular traits described in
      such cultures serve to distinguish these synovial cells from other types of human
      fibroblasts, and several cellular alterations have been found in cultures derived
      from membranes of rheumatoid arthritic patients. One important finding is
      increased resistance of cultured rheumatoid cells to infection with rubella and
      NDV; this and other cellular changes suggest the possibility of an occult virus
      infection in the rheumatoid cells. Such viral persistence could be theoretically
      linked with the immunologic aberrations in rheumatoid arthritis, discussed in
      this symposium.

PMID- 19867376
TI  - Virologic studies in rheumatoid arthritis and other connective tissue diseases.
AB  - A total of 187 specimens from 142 subjects with rheumatoid arthritis, systemic
      lupus erythematosus, other connective tissue diseases, and controls were placed
      in cell culture. Specimens from 119 of the subjects grew, lasting over 2 yr in
      several instances. No evidence of virus infection has been found by a variety of
      sensitive methods, including cell fusion. Other approaches have likewise failed
      thus far to implicate any virus in the pathogenesis of rheumatoid arthritis.

PMID- 19867377
TI  - Immune complex disease in chronic viral infections.
AB  - Chronic viral infections of animals associated with immune complex disease
      resemble a number of human disorders. At present, on the basis of showing (a)
      virus, host antiviral antibody, and C3 deposited in a granular pattern along the
      glomerular capillary wall and in the mesangia and (b) virus-host Ig (presumably
      antiviral antibody) complexes in the circulation, immune complex disease occurs
      in chronic murine infections with LCM, LDV, MSV, and ADM. In addition, granular
      deposits in the glomeruli in Coxsachie B, polyoma, other leukemic viral
      infections in mice, equine anemia, and hog cholera suggest that immune complex
      disease also occurs in these infections. In transplacental LCM infections
      maternal antiviral antibody transferred in utero or via milk induces very early
      and severe immune complex disease. The severity of immune complex nephritis in
      mice neonatally or transplacentally infected with LCM virus is directly
      proportional to the amount of Ig elutable from the kidney and to the proportion
      of this Ig which reacts with the infecting virus.

PMID- 19867378
TI  - The nature of australia antigen and its relation to antigen-antibody complex
      formation.
AB  - There is considerable data to support the hypothesis that Australia antigen is an
      infectious agent that causes hepatitis in man. (a) Association with acute viral
      hepatitis. (b) Association with chronic hepatitis. (c) Virus-like appearance
      under the electron microscope (200-A particles). (d) Transmission of Au(1) from
      man to man. (e) Transmission and passage of partially purified Au(1) to an animal
      host (infant African green monkey). (f) Localization [with fluorescent anti
      Au(1)] of Au(1) in the nuclei of liver cells of patients with hepatitis and/or
      Au(1) in their blood. (g) Distribution of Au(1) in institutions, disease groups,
      and populations is consistent with the distribution of an infectious agent. (h)
      RNA identified in Au(1) particles isolated from blood. (i) Apparent replication
      of Australia antigen in tissue cultures of human liver cells. There is also
      considerable evidence that Australia antigen has many of the characteristics of a
      serum protein polymorphism. Since neither of these hypotheses has been rejected
      they can be combined to make a third hypothesis, namely, that Australia antigen
      is an infectious agent which causes hepatitis in some people infected with it and
      that it has the characteristics of an (inhertied) serum protein polymorphism. We
      propose calling agents of this postulated class "Icrons."

PMID- 19867379
TI  - Vasculitis in association with australia antigen.
AB  - Six patients with biopsy-proven polyarteritis nodosa and chronic Australia
      antigenemia are described. Evidence was found in these patients for the presence
      of circulating immune complexes composed of Australia antigen and immunoglobulin.
      In addition, in two patients immunofluorescent studies localized Australia
      antigen, IgM, and complement in the blood vessel walls.

PMID- 19867380
TI  - Infectious virus-antibody complexes: interaction with anti-immunoglobulins,
      complement, and rheumatoid factor.
AB  - Interaction of antiviral antibody with the virion can result in the formation of
      infectious VA complexes. These complexes have been recovered from the blood of
      chronically infected animals and have been produced in vitro. Incubation of
      infectious VA complexes with specific anti-immunoglobulins or the purified first
      and fourth components of complement resulted in neutralization. With
      subneutralizing concentrations of the first and fourth components of complement,
      neutralization was enhanced by the addition of the second and third components of
      complement. RF attached to infectious VA complexes but failed to produce
      neutralization. The attachment of RF to VA complexes, however, increased the
      susceptibility of these complexes to neutralization by complement. These findings
      support the hypothesis that anti-immunoglobulins and complement result in
      neutralization by more extensive coverage of the surface of the virion than
      occurs with antiviral antibody alone. Other experiments showed that antiviral
      antibody increased the sedimentation of radio-labeled virus and that rate-zonal
      centrifugation could be used to purify VA complexes and to study factors which
      influence the association and dissociation of these complexes. Our experiments
      suggest that in vivo the attachment of accessory factors to infectious VA
      complexes might enhance virus neutralization and play a role in the pathogenesis
      of virus-induced immune complex disease.

PMID- 19867381
TI  - Immune cell cooperation, viruses, and antibodies to nucleic acids in new zealand
      mice.
AB  - The development of autoimmunity in New Zealand mice is related to genetic,
      immunologic, and viral factors. Evidence is presented to suggest that thymus
      dependent immune functions may be depressed and bone marrow-dependent functions
      augmented in these mice. Antibodies to RNA and DNA appear spontaneously and can
      also be induced by treatment with rI.rC. Antibodies binding rI.rC-(14)C in human
      lupus sera, in NZB/NZW F(1) (B/W) mice developing lupus, and in NZB, ALN, and
      ALN/NZB mice have greatest specificity for reovirus double-stranded RNA.
      Treatment of B/W mice with RNA and cyclophosphamide induces immunologic
      tolerance, and suppresses antibodies binding rI.rC-(14)C. During recovery, the
      specificity of the antibodies is unaltered. Induction of tolerance in this way
      prevents the accelerated formation of anti-RNA antibodies normally induced by
      MLV. This finding suggests that virus-accelerated and natural disease occur
      through a similar mechanism, and supports the hypothesis that viruses may act as
      antigenic stimuli for a genetically hyper-responsive antibody-producing system.

PMID- 19867382
TI  - Pathogenesis of immune complex glomerulonephritis of new zealand mice.
AB  - Observations based on elution of IgG from nephritic kidneys of NZ mice and
      absorption of the eluted IgG with selected antigens indicate that their immune
      complex nephritis involves at least two kinds of antigen-antibody complexes.
      Antibodies reactive with nuclear antigens account for nearly half of the IgG
      eluted from the kidneys while antibodies reactive with Gross viral antigens make
      up a significant but lesser amount. Superimposed chronic viral infections affect
      the nephritis of NZ mice in different ways. LCM and polyoma infections hasten and
      intensify the antinuclear antibody responses and glomerulonephritis of these mice
      while LDV infection appears to protect against both antinuclear antibody
      formation and development of nephritis.

PMID- 19867383
TI  - Quantitation of acute and chronic serum sickness in the rabbit.
AB  - The amounts of BSA (immune complex) deposited in glomeruli of rabbits with acute
      and chronic serum sickness were determined using radio-labeled BSA and paired
      label RSA. In animals with acute serum sickness and severe glomerulonephritis,
      about 18 microg of I*BSA were present in both kidneys after immune elimination
      (>99% of the circulating I*BSA). Visible with an immunofluorescent sensitivity of
      0.25 microg per g of kidney, the I*BSA became rapidly undetectable and was
      presumably covered by deposits of circulating host anti-BSA and complement which
      increased demonstrably. In chronic serum sickness produced by daily injections of
      a quantity of BSA to balance antibody production, 0.04% of the daily dose of
      I*BSA was deposited in the glomeruli during the developmental stages of
      glomerulonephritis. Coincident with the onset of overt proteinuric
      glomerulonephritis, the daily I*BSA deposition, rate increased to about 0.5% of
      the daily dose. The half-disappearance rate of I*BSA from the kidney was about 5
      days. Administration of huge excesses of BSA caused a fivefold increase in the
      half-disappearance rate. The accelerated I*BSA disappearance could be correlated
      with vanishing glomerular immunofluorescent deposits of BSA and immunoglobulin,
      as well as electron microscopic dense deposits; however, functional improvement
      of the disease was not observed. The roles of immune complex size, precipitating
      and nonprecipitating (total ABC) antibodies, and RES function in the development
      of chronic serum sickness glomerulonephritis are discussed.

PMID- 19867384
TI  - Mechanisms involved in the deposition of immune complexes in tissues.
AB  - The mechanisms reponsible for the deposition of circulating immune complexes have
      been analyzed. An active process appears to be responsible in both a laboratory
      model in guinea pigs and in acute immune complex disease (serum sickness) in
      rabbits. In rabbits, after the injection of antigen to induce serum sickness,
      immune complexes appear in the circulation. In addition, homocytotropic (IgE)
      antibody is formed which binds to the surface of basophils. Leukocyte suspensions
      containing these basophils, when combined with specific antigen, release a
      soluble factor that causes clumping of platelets and release of their vasoactive
      amines. An excellent correlation was found between the presence of this mechanism
      of release of vasoactive amine and the deposition of immune complexes in serum
      sickness of rabbits. Antagonists of vasoactive amines or depletion of platelets,
      the major circulating reservoir of these amines, suppressed the deposition of
      circulating immune complexes and inhibited glomerulitis and arteritis. Upon
      entering the walls of vessels, the complexes became lodged immune complexes,
      greater than 19S in size, were deposited along the membranes. The data suggest
      that at a time when immune complexes appear in the circulation of an immunized
      rabbit, vasoactive amines are released from platelets in areas where turbulence
      of blood occurs. Sensitized basophils participate in the release of vasoactive
      amines from the platelets. The amines induced increased vascular permeability
      which leads to deposition of large complexes from the circulation in vessel walls
      by a process of filtration. The deposited complexes then induce inflammatory
      injury.

PMID- 19867385
TI  - The c3-activator system: an alternate pathway of complement activation.
AB  - Evidence has accumulated indicating the existence of a second complement
      activation mechanism which is functionally analogous to C1, C2, and C4. The
      noncomplement protein C3PA, previously recognized through its ability to form a
      complex enzyme with a protein from cobra venom, appears to be the precursor of
      the C4,2 analogue. It is a thermolabile beta-globulin with a molecular weight of
      80,000. When serum is treated with naturally occurring plant or bacterial
      polysaccharides, the C3PA is cleaved into at least two fragments, one having the
      electrophoretic mobility of a gamma-globulin and a molecular weight of 60,000,
      and the other being an acidic peptide with a molecular weight of 20,000. The
      larger fragment has the ability to cleave C3 into C3a and C3b and is therefore
      called C3 activator. It arises from the action of an as yet unidentified serum
      enzyme upon the C3PA, which is tentatively called C3PA convertase. In addition to
      endotoxins, yeast cell walls, inulin, and agar, aggregates of immunoglobulins
      were found to be activating substances, including human IgA, guinea pig gamma1,
      and duck antibody. Serum depleted of C3PA had reduced E. coli bactericidal and
      increased hemolytic activity. The relationship of the C3-activator system to
      experimental and clinical observations has been discussed.

PMID- 19867386
TI  - Biological expressions of lymphocyte activation : I. Effects of phytomitogens on
      antibody synthesis in vitro.
AB  - The effects of nonspecific phytomitogens on primary plaque-forming cell (PFC)
      responses of mouse spleen cells to heterologous erythrocytes in vitro were
      studied. Spleen cell cultures treated with concanavalin A or phytohemagglutinin
      in vitro or established with spleen cells derived from mice injected with
      concanavalin A 24 h previously were similarly affected. In both cases,
      submitogenic doses resulted in substantial enhancement of PFC responses, whereas
      10-fold larger doses were profoundly inhibitory. In contrast to the suppressive
      effects of mitogenic doses of phytomitogens added at culture initiation, addition
      of these same doses to cultures 48 h later resulted in increased PFC responses.
      This enhancement could be observed within 1 h after treatment and consequently
      could not be ascribed only to mitotic expansion of the antibody-synthesizing
      clone. Activation of spleen cells with specific antigen before mitogen treatment
      was not required for expression of the enhancing or suppressing effects on PFC
      responses. IgM and IgG PFC responses were similarly affected. Studies of cell
      interactions revealed that as few as 10(5) spleen cells obtained from mice
      treated with concanavalin A in vivo synergistically enhanced the PFC responses of
      10(7) normal spleen cells. This enhancement was mediated by mitogen-activated T
      lymphocytes which were resistant to 2000 R irradiation 24 h after activation. The
      relevance of these observations to emerging concepts of helper and suppressor T
      cell activity is discussed.

PMID- 19867387
TI  - Mixed lymphocyte reactivity against normal cells by splenic lymphocytes from
      tumor-bearing mice : I. Studies of vigorous immune responsiveness induced in f(1)
      mice by parental strain tumor cells.
AB  - The establishment of an intimate connection between autoimmunity and neoplasia
      would require the demonstration of an experimentally induced, tumor-dependent
      autoimmune process. For this reason, we have studied cellular immune reactions of
      mice bearing a transplantable leukemia (L1210). Spleen cells from hybrid BDF(1)
      mice bearing the L1210 tumor (BDFt) reacted vigorously in mixed lymphocyte
      culture with mitomycin-treated, normal spleen cells from mice of the parental
      strain from which the L1210 tumor was derived (DBA/2). Spleen cells from nontumor
      bearing BDF(1) mice reacted only weakly with these parental cells. The BDFt cells
      likewise did not respond when cultured with mitomycin-treated spleen cells from
      the other parental strain (C57B1/6). The vigorous mixed lymphocyte reaction (MLR)
      by BDFt cells against normal parental cells of the same strain as the tumor was
      not due to a double exposure of the reacting cells to histocompatibility antigens
      shared by tumor cells and normal parental cells. The response of cells from tumor
      bearing F(1) mice against normal parental cells seen in these experiments
      suggests the possibility of the induction of an autoimmune-like process against
      host lymphocytes by spleen cells from leukemic mice. Theoretically such a
      phenomenon would considerably reduce an animal's ability to mount an immune
      attack against malignant cells.

PMID- 19867388
TI  - Mixed lymphocyte reactivity against normal cells by splenic lymphocytes from
      tumor-bearing mice : ii. Studies of autoimmune-like activity in completely
      syngeneic and semisyngeneic systems.
AB  - A possible consequence of an antilymphocytic autoimmune process would be serious
      impairment of an animal's ability to destroy tumor cells. One measure of
      autoimmune reactivity of this type would be the demonstration of cellular immune
      responsiveness by cells from tumor-bearing mice against syngeneic normal cells.
      These experiments demonstrate that spleen cells from mice bearing a lymphocytic
      leukemia of identical histocompatability type as the host mounted a vigorous
      immune response against normal syngeneic cells in a mixed lymphocyte reaction
      (MLR). Moreover, ascitic cells from leukemic mice responded significantly to
      normal syngeneic spleen cells in MLR's. The former reactions are usually much
      more vigorous than the responses of normal to malignant cells. These results are
      discussed in terms of the relationship between autoimmunity and neoplasia.
      Alternative explanations necessitated by the dangers involved in the
      interpretation of the immunology of transplantable tumors are considered.

PMID- 19867389
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON LOCALIZED INFECTIONS : FIRST PAPER: ACTION ON THE
      PNEUMOCOCCUS AND ITS EXPERIMENTAL INFECTIONS OF COMBINED SODIUM OLEATE AND
      ANTIPNEUMOCOCCUS SERUM.
AB  - Highly dilute solutions of the alkaline oleates, which do not suffice to alter
      appreciably the morphology or reproductive power of the pneumococci, nevertheless
      produce profound changes in their structure. Pneumococci treated with sodium
      oleate become more subject to autolysis, as is indicated both by the rapidity and
      the perfection of the process of self-digestion, and at the same time they become
      subject to serum-lysis. The serum-lysis of the soaped pneumococci tends to be
      incomplete with normal serum and to be perfect with an immune antipneumococcus
      serum. When normal serum is employed, the surviving pneumococci subsequently
      multiply either in the test tube or in the animal body, in the latter case
      producing fatal infection. When, on the other hand, an immune serum is employed,
      lysis is complete, no multiplication occurs, the test tube mixture is sterilized,
      and the inoculated animal is protected from infection. The inhibition of their
      activity which the soaps ordinarily suffer in the presence of protein, can be
      prevented by the addition of an appropriate quantity of boric acid, so that
      suitable mixtures of serum, soap, and boric acid can continue to exert a
      deleterious and solvent influence on the pneumococci, and the effect is greater
      when immune serum is employed in the mixtures. Infection can not only be
      prevented when the mixture of immune serum, soap, and boric acid is added to the
      pneumococci before injection into the peritoneal cavity of small animals, but the
      infection can likewise be prevented when a therapeutic injection of a mixture of
      the three substances mentioned is made to follow the inoculation of normal,
      highly virulent diplococci. The limits of the activity of the therapeutic mixture
      are determined, in part by the amount of protein to be overcome, and in part by
      the peculiarities of the infection occurring in highly susceptible animal
      species. The virulence of the pneumococci is somewhat diminished by the soap
      treatment, but the treated organisms are not rendered more subject to
      phagocytosis. It would appear that the action of the soap is exerted upon the
      lipoidal moiety of the bacterial cells, through which they are rendered more
      pervious to serum constituents and brought under their deleterious and dissolving
      influence. The changes in the pneuocci here described probably have a prototype
      in the resolving exudate of a pneumonic process; so that it may be considered
      that they occur in the animal body in the course of spontaneous infection and
      constitute one of the conditions of the conquest of the organism by the body's
      forces. A certain conformity exists between the manner of destruction of the
      pneumococci in a pneumonic exudate and that in the artificially prepared soap
      serum mixtures. In order to imitate outside of the body the conditions of the
      removal of pneumococci within the body, it does not suffice merely to study the
      reactions to leucocytes and serum and to conclude from these reactions the means
      which the body employs for the disposal of the diplococci; but it is necessary to
      invoke still other factors, among which are the effects of chemical substances
      present in exudates, of which the soaps represent one class. The failure hitherto
      to unify the reactions in test tubes with those occurring in the body in
      connection with the pneumococcus may be due to the fact that account was not
      taken of this class of chemical bodies. Whether the principle here presented can
      be made applicable to the treatment of local pneumococcus infections in human
      beings is a pressing question. Its application to the treatment of local
      infections, to the seats of which the serum, soap, and boric acid mixtures can be
      directly applied, particularly after evacuation of an inflammatory exudate, seems
      to offer promise.

PMID- 19867390
TI  - THE PATHOGENESIS OF ICTERUS.
AB  - These experiments indicate that, in obstructive jaundice, the bile which escapes
      from the liver is absorbed by the hepatic capillaries and carried by the blood to
      the kidneys. The presence of a thoracic duct fistula influences in no way the
      development of icterus after total obstruction of the common bile duct. Bile
      pigments, sufficient to give a Salkowski test, may or may not appear in the lymph
      of the thoracic duct in such experiments, their appearance possibly depending
      upon the rapidity of bile secretion and the amount of lymph flow. Chronic icterus
      developing in an animal with a thoracic duct fistula gives an interesting
      distribution of bile pigments in the body fluids. The lymph and pericardial fluid
      contain the same amount, which is much less than the content of bile pigment in
      the blood serum and urine. It seems clear that in both acute and chronic
      obstructive jaundice the lymphatic apparatus takes no essential or active part in
      the absorption of bile pigments from the liver. At best, the lymphatic system is
      a secondary factor in the mechanism of jaundice.

PMID- 19867391
TI  - FIBRINOGEN OF THE BLOOD AS INFLUENCED BY THE LIVER NECROSIS OF CHLOROFORM
      POISONING.
AB  - 1. Chloroform anesthesia for two hours or more will cause more or less central
      liver necrosis in dogs, depending on the length of the anesthesia and the
      susceptibility of the animal. 2. If the fibrinogen of the blood of such an animal
      be estimated at intervals, it is found that this proteid shows a drop
      corresponding to the amount of liver necrosis. 3. By administering chloroform,
      the fibrinogen may be almost eliminated from the circulating blood, and the
      poisoned animal may bleed for hours from small skin pricks or cuts. 4. The liver
      can recover from a grave injury due to chloroform and return practically to a
      normal condition in about ten days. 5. The fibrinogen reappears in the blood as
      the liver effects its repair. It seems that the quantity of fibrinogen present is
      a good indicator of the liver efficiency and a fairly accurate index of the
      amount of liver injury. 6. Shortly after the recovery of the liver from an injury
      due to chloroform, one may find an excess of fibrinogen in the blood. 7. In
      severe cases of chloroform poisoning, the calcium of the blood was normal or
      slightly increased, and the thrombin was normal. 8. These experiments give no
      evidence that the formation of thrombin or prothrombin is dependent upon liver
      activity. 9. The hemorrhages of chloroform poisoning are due not to lack of blood
      clotting but to inefficient coagulation. The clot has not the body and toughness
      supplied by the fibrinogen, and is, therefore, unable to check even capillary
      hemorrhage. 10. Fibrinogen is either formed in the liver or is wholly dependent
      upon liver activity for its production.

PMID- 19867392
TI  - CHANGES IN THE PROTEOLYTIC ENZYMES AND ANTI-ENZYMES OF THE BLOOD SERUM PRODUCED
      BY SUBSTANCES (CHLOROFORM AND PHOSPHORUS) WHICH CAUSE DEGENERATIVE CHANGES IN THE
      LIVER.

PMID- 19867393
TI  - ON ARTERIOVENOUS ANASTOMOSIS AND THE MECHANICAL THEORY OF ARTERIOSCLEROSIS.

PMID- 19867394
TI  - ON HEAT-SENSITIVE ANTICOMPLEMENTARY BODIES IN HUMAN BLOOD SERUM.
AB  - The work recorded above has served to corroborate the observations of other
      writers, notably of Noguchi, that in many human sera, if not in all, there
      develop, on standing, anticomplementary bodies which are delicately thermolabile,
      being inactivated by heating to 56 degrees C. for fifteen to twenty minutes. It
      has appeared that these bodies may occasionally be present in sera which, after
      heating, may develop the thermostable anticomplementary body referred to by other
      authors. It has become evident also that the speed of development of the
      thermolabile anticomplementary body in different sera is subject to much
      variation. The thermolabile body appears as the complement disappears. The
      question arises whether the thermolabile anticomplementary body may not be
      originally present in the serum, temporarily masked by the native complement.
      This would seem improbable from the fact that titration has shown that 0.1 and
      0.2 cubic centimeter of the inhibiting serum will often inhibit as much as 0.6
      cubic centimeter of fresh guinea-pig complement, a quantity superior to the
      amount of complement present originally in the antihemolytic serum. It seems,
      therefore, that the anticomplementary body must actually be formed in the serum
      during the period of preservation. The thermolabile antihemolytic body studied by
      us is like the thermostabile body investigated by Noguchi, in that it inhibits
      alien as well as homologous complement; it is unlike the thermostabile body,
      however, in that it cannot be absorbed from serum by digestion with red cells,
      nor does it render the treated cells more resistant to hemolysis. The
      thermolabile body may be removed from inhibiting sera by precipitating the
      globulins. A solution of the glotmiins then manifests a thermolabile
      anticomplementary action. No relationship between a clinical condition and the
      appearance of these bodies in the sera, has been found. As a practical result
      these studies have shown, as have those of Noguchi, that the complement fixation
      tests should never be made with certain sera which have been preserved for some
      time without inactivation.

PMID- 19867395
TI  - BIOCHEMICAL STUDIES ON SO-CALLED SYPHILIS ANTIGEN.
AB  - The liver tissues of man and certain animals (dogs, rabbits, guinea pigs, etc.)
      yield, upon alcoholic extraction, various substances which may be divided by
      their physical and chemical properties into several groups. While many substances
      are present in the alcoholic extract, the ones possessing antigenic properties
      are comparatively few. The latter are responsible for the antigenic properties
      exhibited by the whole alcoholic extract. The substances extracted with alcohol
      were fractionated into the following four groups. (a) Substances Insoluble in
      Ether and Hot Alcohol.-These are chiefly proteins and salts. The proteins are
      probably the minute particles of larger molecules held in apparent suspension in
      alcohol until all other substances are removed. The water extracted from the
      tissues and admixed with alcohol is also an essential factor in extracting these
      particles in an alcoholic solution. The salts present are the usual physiological
      constituents of the liver, notably, sodium chloride. The quantity of these
      substances extracted with alcohol varies greatly with different specimens.
      Biologically considered, they are neither markedly hemolytic nor
      anticomplementary and possess no antigenic property for the Wassermann reaction.
      It is important, however, to note that the proteins bind complement when mixed
      with certain active human sera. For this reason a preparation of antigen
      containing this group of substances is unsuitable for use in combination with an
      active serum, and should, therefore, be rejected. (b) Substances Insoluble in
      Ether and Soluble in Hot Alcohol.-This group contains soaps, cleavage products of
      proteins, and small amounts of the bile salts. Soaps and bile salts are very
      strongly hemolytic and are absolutely unfit for use as antigen. Moreover, their
      antigenic properties are very slight. It is best to eliminate this group of
      substances from the preparation of antigen. The quantity of the substances of
      this group extracted from different specimens of tissue is very variable. (c)
      Substances Soluble in Ether, Alcohol, and Aceton.-In this group are found varying
      amounts of fatty acids, both saturated and unsaturated, some neutral fats,
      cholesterin and many unidentified lipoidal bodies. This group causes either
      hemolysis or inhibition, of hemolysis. In other words, it is anticomplementary as
      well as hemolytic in the majority of preparations. At the same time, in some
      preparations it is, to a certain extent, antigenic. This great variation in the
      amounts of these substances in given extracts renders their presence in the
      antigen preparation undesirable. It is not denied, however, that, when added in
      adequate quantities, some of these substances may improve the activity of the
      antigenic lipoids. (d) Substances Insoluble in Aceton.-This group of substances
      consists of phosphatids. The best known among them is, of course, lecithin.
      Besides lecithin, however, there must be various other phosphatids present in
      this fraction. It will be noticed that the precipitate formed by mixing the
      ethereal solution with aceton contains a certain amount of lipoids insoluble in
      ether as well as in alcohol. Before the fractionation in aceton, all lipoids were
      soluble in ether or ethyl alcohol. Further analytical work on the nature of the
      phosphatids contained in this fraction is necessary. This fraction, in general,
      is more constant in amount in the various liver extracts. Biologically
      considered, it is the most important. It is usually non-hemolytic, frequently
      anticomplementary, but much more strongly antigenic than the other fractions. The
      antigenic strength varies with different preparations, being almost absent in the
      extracts derived from fatty livers. An aceton insoluble fraction may be strongly
      antigenic without any other auxiliary effects, or may be accompanied by an
      anticomplementary property. This fraction does not cause the so-called non
      specific reaction with an active human serum. For these reasons it is recommended
      (as Noguchi has repeatedly done before) that the antigen should be selected from
      the aceton-insoluble fractions. Iodine Value in Relation to Antigenic Value.
      Speaking generally of the aceton-insoluble fraction, a high antigenic value is
      associated with a high iodine value of lipoids obtained from the liver and heart.
      This rule does not, however, apply to the corresponding fraction from the brain.
      Standard Antigen.-The preparation of a standard antigen for Noguchi's method for
      the diagnosis of syphilis is given just before the summary. The directions will
      enable one to make a stock solution, from which, at any time, a suitable
      antigenic emulsion may be obtained.

PMID- 19867396
TI  - VARIATIONS IN THE COMPLEMENT ACTIVITY AND FIXABILITY OF GUINEA PIG SERUM.
AB  - The following conclusions may be drawn from the foregoing series of experiments.
      The complementary activity varies within a definite limit in different specimens
      of guinea pig serum. With sera which stood in contact with the clot for twenty
      hours, the strongest and weakest were in the ratio of 0.015 cubic centimeter to
      0.04 cubic centimeter. The former was 2.66 times stronger than the latter. The
      variation observed with the same series of sera after forty-six hours was still
      more striking. The strongest was 0.013 cubic centimeter, and the weakest, 0.06
      cubic centimeter, that is, the former was 4.6 times stronger than the latter.
      These findings agree with those made by Massol and Grysez. The variations were
      not so marked with the majority of sera. It is noteworthy that a large number of
      the sera gained in the complementary activity when remaining in contact with the
      clot for forty-six hours, while some sera became weakened during the same length
      of time. The amount of serum fixed by given constant quantities of syphilitic
      serum and antigen varies much more markedly than the variations in their
      complementary activity. One serum failed altogether to be fixed. On the other
      hand, one sample of serum was so easily fixable that 0.24 cubic centimeter
      (corresponding to 9.6 complement units of this specimen) disappeared, while the
      average quantity fixed was only 0.098 cubic centimeter (corresponding to 4.64
      complement units). The normal standard of fixability was shown in about 50 per
      cent. of the specimens examined. If the zone of normal fixability is enlarged in
      both directions by one unit, the percentage of normal fixability would become
      65.8. There is no definite relationship between the complementary activity and
      the fixability of a given specimen of guinea pig serum. The facts derived from
      our present experiments, especially in regard to the exceptions in the fixative
      quality of this serum, demand the utmost precaution from those intending to
      employ it for diagnostic purposes, as, for example, in the Wassermann reaction.
      No quantitative work is possible with the complement fixation reaction unless the
      experimenter is capable of determining the fixability of the serum in use. One of
      us (Noguchi) has long realized this source of error, and in order to reduce it he
      has advised the employment of a mixture of sera from more than two guinea pigs.

PMID- 19867397
TI  - THE COMPARATIVE MERITS OF VARIOUS COMPLEMENTS AND AMBOCEPTORS IN THE SERUM
      DIAGNOSIS OF SYPHILIS.
AB  - 1. The maximum activity of an antihuman hemolytic amboceptor may be obtained by
      employing the homologous or heterologous complement, according to the variable
      relations existing between the species furnishing the amboceptor and the one
      supplying the complement. Thus, some amboceptors are best reactivated by the
      complement of the same species, while others may act most strongly when
      reactivated with the complements of certain suitable heterologous species. 2.
      From the above it is clear that the complementary activity of a given serum may
      be very variable according to the varieties of amboceptors employed. In
      expressing the complementary activity of a serum, the species of the host of the
      amboceptor must always be stated. Thus, one serum may have many different
      complementary titers according to the amboceptors used. A similar variation in
      the titers of the amboceptors occurs when a variety of complements are employed.
      3. Certain species of animals (pig and sheep) yield sera which are comparatively
      poor in reactivating most varieties of antihuman amboceptors. The complements of
      these species deteriorate rapidly. 4. The serum of chicken contained but little
      complement for the amboceptors derived from the mammalia, while the amboceptor
      from the chicken was only poorly, or not at all, reactivable by the complements
      contained in the mammalian sera. The serum of pig was the only variety which
      reactivated this amboceptor in a fair degree. 5. For the fixation tests guinea
      pig complement is the most favorable. This complement is also the most active and
      durable of those which have been studied. The complements of pig and sheep are
      quite fixable, but their weakness and rapid deterioration render them unsuitable
      for fixation purposes. Rabbit complement is quite active but is not easily
      fixable. Goat complement is, as already stated, difficult to fix, in spite of its
      strong complementary activity. The other complements are unsuitable because of
      their feeble complementary activity. 6. For fixation tests the antihuman
      amboceptors produced in the rabbit and guinea pig are suitable. They are,
      moreover, very active and do not cause the phenomenon of non-fixation. The
      amboceptors from other animals are unsuitable, as we cannot find a complement
      which strongly reactivates them. The amboceptor from the goat is unsuitable
      because of the danger of masking the fixation phenomenon by subsequent hemolysis.
      7. In summing up, we arrive at the conclusion that the rabbit is the best animal
      for producing antihuman amboceptor, and the guinea pig for supplying complement.
      The guinea pig produces a good amboceptor, but its small size renders it second
      in choice. So far, no other animals have been found useful for the fixation
      experiments.

PMID- 19867398
TI  - THE INTERFERENCE OF INACTIVE SERUM AND EGG-WHITE IN THE PHENOMENON OF COMPLEMENT
      FIXATIONS.
AB  - The fixing property of a specific precipitate and of syphilitic serum in the
      presence of certain antigenic lipoids, can be removed by adding certain non
      complementary proteins of blood serum or hen's egg. This disappearance of the
      complementary activity in the syphilis reaction, as well as in the true Bordet
      Gengou reaction, is a phenomenon which incidentally accompanies the fixation of
      certain serum constituents, some of which possess a complementary activity. The
      presence or absence of the complementary property in these protein components
      does not influence fixation. Whether the disappearance of the complementary
      activity during the phenomenon of so-called fixation is due to a mechanical
      precipitation of the molecules through absorption or whether it is due to a
      physico-chemical alteration of the active molecules, is unknown. It is more
      probable that a chemical interaction takes place in the case of the syphilis
      reaction. Certain sera, for example, those derived from man and goat, show a low
      fixability. It is interesting to note that the fixability is gradually diminished
      when these sera and egg-white are heated to a temperature above 56 degrees C.,
      and totally disappears at 85 degrees C. The coagulation of proteins with absolute
      alcohol or by boiling, destroys their interfering property. The fact that the
      fixation is not selectively directed towards complement, has a very important
      meaning for exact serology. The one-sided accuracy as to the complementary unity
      is no longer sufficient for quantitative work. Both the complementary and the
      volumetric unity of a serum serving as the source of complement should be taken
      into consideration. Besides, the fixability of the sera of various species of
      animals must also be considered. From these facts a formula may be derived for
      deciding the degree of suitableness of a serum. see PDF for Equation X is the
      degree of suitableness; K, the species constant for the fixability; P, the
      complementary activity; and V, the volume of serum. It will be seen that the
      suitableness is proportional to the fixability constant and the complementary
      unity, and inversely proportional to the volume of serum employed. As to what
      species yields the largest value for X, we refer the reader to our studies
      published elsewhere.

PMID- 19867399
TI  - A HISTOLOGICAL STUDY OF THE SKIN LESIONS OF PELLAGRA.
AB  - The cutaneous lesions in pellagra consist of an early erythema, or, in occasional
      cases, of vesicles or bullous formations which are followed by hyperkeratosis and
      pigmentation, resulting in a dry, dark brown scaliness. These various lesions are
      similar to those normally produced by the action of sunlight, but are much more
      marked. The histological phenomena of the erythematous and bullous stage are
      those of a mild acute inflammatory reaction, together with a degeneration in the
      superficial layers of the corium. Following this degeneration, which involves not
      only the general connective tissue but the connective tissue of the blood
      vessels, there is a reparative change evidenced histologically by an increased
      cellularity of the corium and the presence of fibroblasts. The capillaries also
      are increased in number and much dilated. Apparently as a result of this
      increased vascularity of the corium, there is an increased proliferation of the
      epithelium resulting in a thickening of the epidermis. This increase in thickness
      of the epithelial layer is especially marked in the prickle cells and the stratum
      granulosum. In the later stages, in an effort to secure a firm basement membrane,
      the epithelium is seen to dip down deeply into the rarefied connective tissue.
      About the blood vessels during the reactionary process are found collections of
      lymphoid cells, a few plasma cells, but no mast cells or eosinophiles. That the
      irritant producing the degeneration in the corium is sunlight in the presence of
      some predisposing factor, is suggested by the enormous increase in pigment
      formation in the epithelial cells and by the large number of chromatophores in
      the superficial layers of the corium. This pigmentation is autochthonous in both
      types of cell. There is no reason for believing that the pigment is formed in the
      cells of the corium and thence discharged into the epithelium, or that the
      reverse process takes place. The predisposing factor inducing the changes in the
      corium is, apparently, a lessened resistance of the epithelium to the violet and
      ultra-violet rays, due to some metabolic insufficiency on the part of the
      epithelial cells. Further observation may justify the conclusion that throughout
      the body, pellagra is a disease essentially of the epithelium, including the
      nervous system, this pathological condition manifesting itself by an insufficient
      or altered function.

PMID- 19867400
TI  - AN EXPERIMENTAL CONTRIBUTION TO THE STUDY OF CARDIAC HYPERTROPHY.
AB  - 1. Hypertrophy induced by the production of aortic insufficiency involves all the
      chambers of the heart. The greatest absolute increase in weight is in the left
      ventricle. The remaining segments, arranged in the order of decreasing increments
      are septum, right ventricle, and auricles. The greatest relative increase is also
      in the left ventricle, but the auricles show a relative hypertrophy greater than
      that of the septum or right ventricle. 2. The co-hypertrophy of the auricles is
      not due to an altered venous pressure, but results from an increased force of
      auricular systole. 3. The heart shows an increase in weight within one week after
      the production of aortic insufficiency. The increase in weight is due only in
      part to an increased water content.

PMID- 19867401
TI  - SUBLIMATE AND THE SERUM DIAGNOSIS OF SYPHILIS.

PMID- 19867402
TI  - BARIUM SULPHATE ABSORPTION AND THE SERUM DIAGNOSIS OF SYPHILIS.
AB  - The so-called syphilitic antibodies can be removed from a serum by means of
      absorption with barium sulphate. The removal is due either to an adsorption or a
      mechanical absorption. The activity of the syphilitic antibodies is thereby
      unimpaired. The readiness with which the absorption is accomplished with barium
      sulphate varies considerably with different syphilitic sera. That barium sulphate
      exerts the same absorbing effect upon non-syphilitic serum components is made
      evident by the interfering property which the latter manifest in the absorption
      experiment of the syphilitic antibodies. The selective removal of the serum
      components, other than the syphilitic antibodies, by means of barium sulphate
      absorption is, therefore, impossible. On the other hand, a partial removal of
      these components, with but little removal of the syphilitic antibodies, may be
      effected when the content of a given serum is poor in syphilitic antibodies and
      comparatively rich in the indifferent serum components. But this is impossible if
      the conditions are reversed. The main reasons why some negative syphilitic sera
      may be so modified by the barium sulphate treatment as to give positive
      reactions, are explained below, but these apply only to those methods in which
      inactivated serum is employed. The inactivation reduces the antibody content to
      about one-fourth to one-fifth of the original. When the serum is very rich in
      antibodies, this does not affect the result of the fixation test. But when the
      amount of the antibodies is small, the process of inactivation creates conditions
      quite unexpected. It may produce such a condition that a given amount of the
      serum contains, after inactivation, only one or two antibody units, while the
      other serum components remain undiminished. Here one must not lose sight of the
      vital fact that these apparently indifferent serum constituents are not at all
      indifferent in the fixation processes. They may possess affinities which are
      similar to those of complement for the fixing combination of syphilitic serum and
      antigen. Speaking quantitatively, one unit of the syphilitic antibodies plus
      antigen will fix 0.1 cubic centimeter of guinea pig complement, but this unit can
      also be saturated and blocked by nearly the same amount of the seemingly
      indifferent serum component of the serum to be tested. Moreover, the regular
      amount of inactivated serum used in the Wassermann system is 0.2 cubic
      centimeter, a quantity sufficient to saturate two units of the fixing
      combination. Fortunately, this self-saturation of the syphilitic antibody-antigen
      combination by the other serum components is not constant in occurrence, owing to
      the wide variations of the fixability of the serum components of man. Here the
      benefit of Wechselmann's procedure becomes obvious. By removing a surplus of the
      fixable indifferent serum components by means of barium sulphate, the serum is
      made to react positively, or more strongly than before the treatment with barium
      sulphate. This masking of the positive reaction through the self-saturation is
      liable to occur in any system in which inactivated serum is recommended. Another
      equally important factor in masking the positive reaction in a serum in which the
      antibodies are poor, is the presence in considerable amount of natural antisheep
      amboceptor in human serum. It is a plain and simple fact that an excess of
      hemolytic amboceptor renders a positive reaction feeble or completely negative.
      As we have shown in our present investigation, a hemolytic amboceptor can be
      removed from the serum by means of absorption with barium sulphate. Thus it is
      easy to understand why Wechselmann found that barium sulphate absorption improves
      the reaction in the original Wassermann system. The treatment of syphilitic serum
      with this salt can have a twofold benefit in the case of the original method of
      Wassermann; namely, the removal of certain interfering serum components and the
      removal or diminishing of the natural antisheep amboceptor present in the
      syphilitic serum. In the method of Noguchi, there is no necessity for applying
      the barium sulphate absorption. Noguchi recommends the use of unheated serum,
      hence the absolute amount of the serum employed is only one-half of the absolute
      amount of complement. Eventually an old serum may be anticomplementary and need
      inactivation, but if the result is doubtful in this instance, a fresh serum from
      the same patient may be secured and subjected to reexamination. In this method
      there is no danger of introducing an amount of hemolytic amboceptor which is both
      unknown and uncontrollable, for the reason that human serum is usually devoid of
      isolysin (antihuman hemolytic amboceptor), and, if the latter is present, it
      never reaches the strength which shows any effect upon the hemolytic system
      employed. We conclude, therefore, that the barium sulphate absorption is to be
      recommended for the original method of Wassermann under certain conditions, but
      that it is unnecessary for the antihuman hemolytic system of Noguchi.

PMID- 19867403
TI  - EFFECTS OF MECHANICAL AGITATION AND OF TEMPERATURE UPON COMPLEMENT.
AB  - 1. Under certain conditions, mechanical agitation destroys the complementary
      activity of guinea pig serum. It is most injurious when carried out constantly at
      a temperature of 37 degrees C., but it is extremely insignificant at 10 degrees
      C. After the first few hours at 37 degrees C., the destruction of complement
      proceeded much more rapidly, and after six hours it was almost complete. On the
      other hand, within one hour shaking had almost no destructive effect on
      complement, even at 37 degrees C. From this we may conclude that the several
      shakings which are necessary for fixation experiments during incubation do not
      modify perceptibly the outcome of the reactions. 2. The rate of destruction of
      the complement of guinea pig serum at temperatures above 45 degrees C. is
      progressively greater as it approaches 55 degrees C., at which temperature the
      activity is reduced in thirty minutes to one-thirtieth to one-fortieth of the
      original strength of the unheated serum; but it is not completely destroyed, as
      is commonly assumed. The velocity of destruction of guinea pig complement when
      exposed to 55 degrees C. for various lengths of time is found to be quite
      irregular, and not proportional to the length of time. This irregularity,
      however, presents a certain rhythm, a period of greater destruction alternating
      with one of less destruction.

PMID- 19867404
TI  - MORPHOLOGICAL CHANGES OBSERVED IN A MOUSE CARCINOMA IN THE COURSE OF LONG
      CONTINUED TRANSPLANTATION, AND THE INFLUENCE OF AN EXPERIMENTALLY PRODUCED
      DECREASE IN THE GROWTH-ENERGY OF THE TUMORS UPON THEIR MORPHOLOGICAL CHARACTER.

PMID- 19867405
TI  - THE RELATIONS OF EMBRYONIC TISSUE AND TUMOR IN MIXED GRAFTS.
AB  - Implanted mixtures of mouse embryo and tumor sometimes result in an excellent
      growth of both. To assure this, it is necessary that the tumor selected be one
      which proliferates slowly, because more active ones prevent the development of
      the fragments of embryo. Transplanted embryonic tissue (of the type used) does
      not, at its best, grow as rapidly or in so large a percentage of hosts as some
      tumors. The morphological relations between tumor and embryonic tissue in the
      mixed graft are often intimate. Apparently either may adapt the other to its
      structural purposes. Occasionally a direct union takes place between cancerous
      epithelium and that of the embryo, with result in pictures suggesting an origin
      of one from the other. This observation has considerable significance in view of
      the current reliance upon just such histological data to prove that cancer arises
      from normal epithelium.

PMID- 19867406
TI  - THE EFFECT OF PREGNANCY ON IMPLANTED EMBRYONIC TISSUE.
AB  - 1. Grafts of embryonic tissue obtained at operation and implanted in the mother,
      will grow well in case she no longer carries young. The growth is no more rapid
      than that in favorable nonpregnant aliens, but persists for a longer period
      without retrogression and results in a greater variety of tissues. The
      superiority of auto-transplantation over iso-transplantation is responsible for
      this fact. No evidence of a specific "growth-substance" peculiar to the pregnant
      state is furnished by the experiment. 2. When a mouse is implanted with embryonic
      tissue from her own uterus, and she still carries developing young, the fate of
      the grafts is very different from that just described. They are vascularized from
      the host but fail to grow or differentiate. Yet they do not die, and after
      pregnancy is concluded they may start to grow. The finding is strikingly like
      that noted by others of implanted tumor in pregnant hosts. It seems probable that
      some general factor affecting the growth of implanted tissues is here concerned.

PMID- 19867407
TI  - THE INFLUENCE OF MOUSE-RAT PARABIOSIS ON THE GROWTH IN RATS OF A TRANSPLANTABLE
      MOUSE SARCOMA.
AB  - The results in these experiments seem to justify us in concluding that the growth
      of mouse tumors in rats is very definitely promoted by mouse-rat parabiosis, the
      percentage of " takes" being markedly increased, the rate of growth accelerated,
      and the duration of active growth extended to at least seventeen days. These
      findings are in accord with Ehrlich's hypothesis, although, on account of the
      complexity of the factors involved in such experiments, other explanations may be
      advanced.

PMID- 19867408
TI  - THE AESTIVO-AUTUMNAL PARASITE: ITS SEXUAL CYCLE IN THE CIRCULATING BLOOD OF MAN,
      WITH A DESCRIPTION OF THE MORPHOLOGICAL AND BIOLOGICAL CHARACTERISTICS OF THE
      PARASITE.
AB  - 1. The description of two distinct types of aestivo-autumnal crescentic parasites
      given by Craig in Osler's Modern Medicine (with difference in extremities, amount
      and form of pigment, double-outline, etc.), I have been unable to confirm. 2. The
      crescentic parasite is throughout its entire existence extracellular (i. e., not
      within the substance of the red corpuscle, but attached to its surface). It
      develops from the familiar small ring-form parasite, retaining a circular contour
      until fully matured. 3. The very young ring-form parasite has no capsule; the
      macrogamete has one during its development and sexual activity; while the
      microgametocyte has it only during its development. 4. The Sexual Cycle of the
      crescent may occur in the circulating blood of its human host. This cycle is
      probably very rapid, for practically the whole cycle can be seen in a few smears
      taken from one puncture. The microgametocyte, or male, develops a flagellum
      (microgamete) which, after the parasite has assumed the crescentic phase, leaves
      the body of the parasite and enters the body of the macrogamete, or female,
      during its existence as a round body. Fertilization is then accomplished. 5. The
      microgametocyte, after the escape of the flagellum, shows evidence of
      degeneration and is probably cadaveric. 6. After fertilization, the macrogamete
      assumes the crescentic form, reaches the reproductive phase and undergoes
      sporulation, the product of which appears to be the small ring-form parasite,
      Renewed infection of the red cells then takes place. 7. That the sexual cycle is
      not seen oftener in the circulating blood of man may be due to one or more of the
      following reasons: (a) The process of reproduction may be and probably is very
      rapid (some forms of protozoa are exceeded in rapidity of reproduction only by
      bacteria). (b)The cycle may usually take place in some of the internal organs.
      (c) It may be that the sexual cycle occurs in the peripheral blood only at
      intervals, when it becomes necessary for the parasite to renew its exhausted
      vitality. (d) The occasional occurrence of the sexual cycle in the circulating
      blood may be due to some slight chemical change in the composition of the host's
      blood serum. 8. I find no good evidence of conjugation-forms in aestivo-autumnal
      malaria. I found some of the young ring form parasites in close approximation or
      overlying each other. As the sexual cycle does take place in the blood of man,
      such a process of conjugation would seem unnecessary, unless it occurred as an
      atypical process. The fact that the crescent is more resistant to quinine than
      the other varieties of malarial parasites might be explained by the presence of a
      capsule which appears to protect the parasite, certainly during the sexual phase
      and probably during the " resting " period (when not undergoing sexual changes).
      The youngest form of ring parasite shows no evidence of encapsulation. This may
      explain the fact that quinine is best administered just before the paroxysm when
      the parasite is undergoing segmentation.

PMID- 19867409
TI  - MALARIAL PIGMENT (SO-CALLED MELANIN): ITS NATURE AND MODE OF PRODUCTION.
AB  - 1. Two important methods for the study of malarial pigment are described. (a) A
      method for obtaining a solution of malarial pigment from fixed tissues without
      the removal of a trace of hemoglobin from the red blood corpuscles. (b) A method
      for obtaining an iron reaction in malarial pigment. 2. By comparing the bleach
      reactions and solubility of melanins and malarial pigment, the dissimilarity of
      the two classes of pigments has been demonstrated. 3. The spectroscopic
      examination of a solution of malarial pigment proves conclusively that the
      pigment is hematin. 4. It is suggested that the action of a proteolytic enzyme of
      the malarial parasite upon the hemoglobin of the red blood corpuscle is the most
      probable mode of elaboration of malarial pigment. 5. The difficulty with which
      the human organism disposes of malarial pigment indicates that the production of
      hematin cannot be considered as a normal intermediate process in the formation of
      bile pigments from hemoglobin.

PMID- 19867410
TI  - CHEMICAL STUDY OF THE BRAIN IN CASES OF DEMENTIA PRAECOX.

PMID- 19867411
TI  - THE BLOOD SUPPLY OF THE KIDNEY. V. THE INFLUENCE OF THE VAGUS NERVE UPON THE
      VASCULARITY OF THE LEFT ORGAN.

PMID- 19867412
TI  - CALCIUM METABOLISM IN A CASE OF INFANTILE TETANY.

PMID- 19867413
TI  - OBSERVATIONS ON THE SUCCUS ENTERICUS.
AB  - Nitrogen equivalent to about 35 per cent of the nitrogen intake, though not
      necessarily derived directly from it, is daily secreted in the succus entericus
      in dogs on a mixed diet; about 10 per cent is excreted in the feces. and about 25
      per cent is reabsorbed. The amount of reabsorbed nitrogen-containing material is
      considerably larger if the bile and pancreatic secretion are included. The
      metabolic significance of this reabsorption can only be surmised. That it is
      probably of great importance is indicated by the fact that in the experiments
      here recorded the amount of nitrogen reabsorbed equaled approximately 25 per cent
      of the nitrogen intake.

PMID- 19867414
TI  - ON ABSORPTION FROM INTRAMUSCULAR TISSUE.
AB  - Injections of adrenalin or other substances into the lumbar muscles of rabbits
      are followed by a rapid absorption in whole or in part of these substances. The
      rapid absorption is not due to the needle being within a vein or to the tearing
      of veins by the needle during its insertion. Similar injections into gluteal
      muscles fail to give reliable results.

PMID- 19867415
TI  - THE RELATIONS OF THE INTERSTITIAL CELLS OF LEYDIG TO THE PRODUCTION OF AN
      INTERNAL SECRETION BY THE MAMMALIAN TESTIS.

PMID- 19867416
TI  - A HISTOLOGICAL AND CHEMICAL STUDY OF THE FATTY MATTER OF NORMAL AND CRYPTORCHID
      TESTES.
AB  - 1. About 19 per cent. of the dry weight of the normal pig testicle is fatty
      matter. Histologically this fat occurs largely in the cells of the seminal
      tubules, and especially in the Sertoli cells. 2. During spermatogenesis the fat
      of the Sertoli cell passes inward for the nutrition of the spermatids and
      spermatozoa. During this passage its character is altered from a neutral fat to a
      lipoid. 3. About 30 per cent. of the dry weight of the cryptorchid pig testicle
      is fatty material. Histologically this fat lies within the seminal tubules,
      partially filling the Sertoli cells. The spermatogenic cells have completely
      disappeared. 4. We conclude that the presence of such an excessive amount of fat
      in the cryptorchid testicle is due to the absence of the spermatogenic cells
      which normally utilize during their development the fat furnished by the Sertoli
      cells.

PMID- 19867417
TI  - THE CULTIVATION OF THE LEPROSY BACILLUS FROM THE HUMAN TISSUES WITH SPECIAL
      REFERENCE TO THE AMINO-ACIDS AS CULTURE MEDIA.
AB  - In the cultivation of Bacillus leprae the initial multiplication outside the body
      cannot be obtained unless amino-acids are present in the medium. The amino-acids
      are believed to be essential nutritives for the initial growth of the organisms.
      It has been demonstrated that the primary growth of the leprosy bacilli occurs
      only in the presence of the products of tryptic digestion. Hence, putrefactive
      and other bacteria which are capable of splitting nucleo-proteids into their end
      acid products are, in consequence, of value in the isolation and cultivation of
      the leprosy bacilli. Amebae are not necessary for securing the primary
      multiplication of the leprosy bacilli upon artificial media and are detrimental
      since they feed with avidity upon the bacilli themselves. Two methods may be
      employed for recovering in culture Bacillus leprae from the tissues. In one (the
      direct), tryptophane or a mixture of albumen and trypsin are employed with a
      culture medium; in the other (indirect), bacterial species capable of digesting
      the albumen constituent of the culture medium are introduced into the medium. In
      both, the end result is identical, since they both provide for the presence of
      the amino-acids in the medium, without which the primary multiplication of the
      leprosy bacilli cannot be secured.

PMID- 19867418
TI  - THE EXPERIMENTAL PRODUCTION OF LEPROSY IN THE MONKEY (MACACUS RHESUS).

PMID- 19867419
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON LOCALIZED INFECTIONS : SECOND PAPER: LYSIS OF THE
      PNEUMOCOCCUS AND HEMOLYSIS BY CERTAIN FATTY ACIDS AND THEIR ALKALI SOAPS.

PMID- 19867420
TI  - CULTIVATION OF TISSUES IN VITRO AND ITS TECHNIQUE.

PMID- 19867421
TI  - A SARCOMA OF THE FOWL TRANSMISSIBLE BY AN AGENT SEPARABLE FROM THE TUMOR CELLS.

PMID- 19867422
TI  - THE TREATMENT OF YAWS (FRAMBOESIA) WITH ARSENOBENZOL (SALVARSAN).

PMID- 19867423
TI  - CULTIVATION IN VITRO OF THE THYROID GLAND.
AB  - The thyroid gland of mammals can be cultivated outside the body. The proliferated
      elements consist of connective tissue and epithelial cells, the former
      predominating. The cells survive in cultures for two weeks or longer, which
      period can be increased by secondary and sometimes by tertiary cultivations. It
      is to be noted that the method of growing in vitro organs such as the thyroid
      gland may come to be used with advantage in the study of the substances concerned
      with the internal secretion of certain glands.

PMID- 19867424
TI  - CICATRIZATION OF WOUNDS IN VITRO.

PMID- 19867425
TI  - STUDIES IN ISOAGGLUTINATION : I. TRANSFUSION AND THE QUESTION OF INTRAVASCULAR
      AGGLUTINATION.
AB  - 1. Intravascular agglutination can occur, and is the probable cause of occasional
      untoward symptoms, or even death, following transfusion of agglutinative blood.
      In the majority of cases, however, it does not occur, or if it does, it causes no
      symptoms. This is dependent on the influence of three factors: (1) concentration
      of the agglutinin; (2) absorption of the agglutinin by an excess of agglutinable
      cells; (3) interference with agglutination by an excess of non-agglutinable
      cells, so that when clumps occur they are microscopic in size. 2. If, for a given
      transfusion, a non-agglutinative donor, i. e., a donor whose blood is of the same
      agglutinative class as the patient's, can not be obtained, then it is safer to
      use a person whose serum is agglutinative toward the patient's cells than one
      whose cells are agglutinated by the patient's serum. 3. Tests for agglutination,
      as well as for hemolysis, ought to be made before transfusion. When time does not
      permit this, one has to weigh the possible dangers of agglutination or hemolysis
      against the dangers of letting the patient go without transfusion. 4.
      Agglutinable cells when transfused are taken up by the phagocytes in the
      patient's blood; and, for this reason) the transfusion of agglutinable blood,
      even when no accident happens, can be expected to do little permanent good.

PMID- 19867426
TI  - CHANGES IN NITROGENOUS METABOLISM AFTER PARATHYROIDECTOMY.

PMID- 19867427
TI  - FURTHER OBSERVATIONS AND EXPERIMENTS ON THE SO-CALLED THYROID CARCINOMA OF THE
      BROOK TROUT (SALVELINUS FONTINALIS) AND ITS RELATION TO ENDEMIC GOITRE.
AB  - In a series of observations upon the thyroids of brook trout, extending from the
      time of hatching to fish of four or more years old, we have been able to follow
      step by step the development of thyroid hyperplasia. In these hatchery trout,
      thyroid overgrowth may be recognized anatomically at the end of the second month
      of extra-oval life. Under the conditions in which these fish live, the thyroid
      overgrowth progressively increases, at first filling the aortic space and then
      invading the surrounding bone and muscle. In our series, this extension into the
      adjacent tissues was not recognizable until the fourth month of extra-oval life.
      The time when invasion of the surrounding tissues is first noticed is, of course,
      subject to great variation in different years and different hatcheries, depending
      on the general hygienic conditions, food, water supply, etc. If the growth
      continues, as it usually does, throughout the rapid growing period of the fish,
      it may first be detected clinically by a reddening of the pharyngeal floor as the
      thyroid tissue spreads to the submucosa. Later, definite external goitres appear
      ventrally. These may be present as early as the sixth month of life. The thyroid
      being, as in mammals, most active during the growing period, the greatest number
      of visible goitres appear during the second and third years of life. In older
      fish the thyroid again becomes less active and there is a tendency toward
      spontaneous recovery. There is no noteworthy change in the anatomical appearance
      of the thyroid growth, whether seen in very young or in older fish, other than
      that clearly dependent on the age of the fish, mechanical factors, as size of the
      goitre, and complicating factors, as infection, hemorrhage, degeneration, etc.
      There exists, therefore, no anatomical basis for the diagnosis of cancer in the
      older fish that is not also present in the youngest fish with thyroid
      hyperplasia. All the appearances of invasion, atypical cell growth, etc. are the
      results of the progressive growth and consequent extension of a non-encapsulated
      epithelial tissue along the paths of least resistance. In many of the larger
      goitres there are more or less distinct areas of thyroid hyperplasia,
      histologically different from the surrounding thyroid tissue, which we look upon
      as benign tumors comparable to the benign tumors seen in human goitres. We class
      them as tumors because they do not react with iodin as does the ordinary
      hyperplasia. To call these tumors cancer is going beyond our present knowledge
      and is unjustified, even though analogy with mammalian tumors suggests that
      certain ones might proceed to true carcinomata. The most common type of the
      benign tumors is the arborescent-papillomatous form and its many modifications.
      Infection is a frequent complication in the larger goitres, for the reasons
      given. It is necessary to recognize this factor in interpreting the histological
      conditions met with, as otherwise, using mammalian standards, some of the
      appearances observed could easily be mistaken for sarcoma. The effect of iodin on
      the thyroid hyperplasia has been studied in the early, middle, and late stages.
      All stages react with iodin, the mild degrees seemingly more rapidly than the
      severer degrees. Thus the early stages undergo involution in from two to three
      weeks, while the late stages may require one to two months. The process,
      therefore, is slower than the iodin reaction time in mammalian hyperplasia. True
      tumors do not react with iodin as does ordinary hyperplasia. Infection or other
      complication modifies the reaction. The reaction with iodin is a specific test
      for functional hyperplasia of the thyroid. As we have not been able to find any
      stage in the process that does not react with iodin, we must conclude that there
      is none that may be looked upon biologically as cancer. Just as iodin invariably
      stops the hyperplasia and causes the thyroid to return to the colloid or resting
      state (from which it may undergo hyperplasia a second, third, or more times,
      exactly as in mammals), so also spontaneous involution occurs when the fish are
      transferred to a natural environment. This spontaneous involution has been
      followed in experiments and has been seen in examples taken at random from the
      streams. We have never seen an exception to this rule, save in the case of true
      tumors. As pointed out above, recovery does not imply a disappearance of the
      goitre; it implies a cessation of growth and return of the active hyperplasia to
      the colloid or resting stage. Thyroid hyperplasia is a compensatory reaction, the
      exact cause of which is still to be sought. There is no evidence that in fish or
      in man it is either infectious or contagious. All the biological data at present
      available favor the view that fish goitre in common with mammalian goitre is the
      symptomatic manifestation of a metabolic and nutritional disturbance. There are
      three major conditions which, in some way still obscure, influence the thyroid
      growth; namely, a limited water supply, overcrowding, and overfeeding with a
      highly artificial and incomplete food. The water of the hatchery observed is not
      intrinsically goitre-producing, as the fish will not develop goitre unless at
      least the factor of overfeeding with an incomplete food operates at the same
      time. On the other hand, they recover if the overfeeding and overcrowding are
      corrected, although they remain in the same water. Therefore it seems probable
      that the food is the major factor acting to bring about a fault of nutrition
      favorable for goitre development. It is impossible at this time to suggest what
      elements in the food may be at fault, whether, for example, it is deficiency or
      excess or disproportion in the relative food values.

PMID- 19867428
TI  - THE VALUE OF HYDROGEN PEROXID IN THE MICROCHEMICAL DETERMINATION OF IRON.
AB  - 1. It has been shown that hemoglobin in solution or within the red blood
      corpuscles can be oxidized by hydrogen peroxid to form a colorless substance
      capable of manifesting a microchemical reaction for iron, the type of the
      reaction depending upon the degree of oxidation. 2. It has been further shown
      that hematin and hemin, when treated with hydrogen peroxid, are decolorized. The
      colorless or nearly colorless body, preserving the form of the original body and
      being an intermediate product of its oxidation, will also exhibit a typical
      reaction for iron. 3. A method has been described for obtaining microchemical
      reaction for iron from hemoglobin and its various modifications and iron
      containing derivatives, from tissue cells, from cell nuclei, and from eosinophil
      granules, by an appropriate degree of oxidation with hydrogen peroxid.

PMID- 19867429
TI  - VACCINE TREATMENT IN THE PREVENTION OF DYSENTERY IN INFANTS.
AB  - This investigation is very limited and the number of patients treated is few, yet
      the following conclusions may not be amiss:- 1. The vaccine in no instance did
      harm, and the reactions in the majority were very mild and of short duration. 2.
      Cases in which bacteriologically B. dysenteriae were proved to be present, but in
      a clinically unrecognizable form, were not affected differently from those which
      were culturally negative. This may in part be due to the fact that this mode of
      vaccination produces an immediate passive immunity, while the bacterial vaccine
      is producing an active immunity. 3. The work is of interest and holds out a
      possible means of preventing the great mortality from infantile dysentery during
      the summer months.

PMID- 19867430
TI  - CHARACTERISTICS OF GROWTH OF SARCOMA AND CARCINOMA CULTIVATED IN VITRO.
AB  - 1. The transplantable sarcomata of rats and mice grow very readily by the method
      of cultivating tissues in vitro. 2. Sarcomatous tissue grows in conformity to a
      type which may be regarded as characteristic for tissues of mesenchymal origin.
      3. The growth of sarcoma cells in vitro consists in ameboid wandering into the
      surrounding plasma, karyokinetic proliferation. and evidences of active
      metabolism on the part of the cells. 4. Mouse carcinomata can be cultivated in
      vitro. The outgrowth of carcinoma cells assumes a sheet-like form, only one cell
      in thickness. They migrate into the plasma by ameboid movement, the advancing
      edge showing numerous prolongations of the cytoplasm into pseudopods. 5.
      Karyokinetic figures are frequently seen in growing carcinoma cells. The cells
      show evidences of active metabolism. 6. Both sarcoma and carcinoma cells
      cultivated in vitro show active phagocytosis; carmin particles placed in the
      plasma are taken up rapidly by the growing cells.

PMID- 19867431
TI  - A STUDY OF CANCER IMMUNITY BY THE METHOD OF CULTIVATING TISSUES OUTSIDE THE BODY.
AB  - 1. Sarcoma cultivated in plasma from immune animals grows quite as vigorously as
      in plasma from normal and tumor-bearing animals, thus affording further proof of
      the absence of specific cytolytic substances in the body fluids of animals immune
      to transplantable cancer. 2. Animals may be successfully inoculated with sarcoma
      cultivated in vitro, although, in the case of rat sarcoma, there is evidence of
      diminished virulence. 3. Subcultures of sarcoma cultivated in vitro may be made
      by transferring to fresh plasma the original piece of tissue, or a portion of the
      outgrowth. The duration of life of sarcoma cells under these conditions seems
      dependent only on a renewal of the medium.

PMID- 19867432
TI  - STUDIES ON IMMUNITY IN CANCERS OF THE WHITE RAT : THE SIGNIFICANCE OF ATHREPSIA.

PMID- 19867433
TI  - THE RELATION OF CERTAIN BACTERIA TO NON-SPECIFIC REACTIONS WITH THE COMPLEMENT
      FIXATION TEST FOR LUES.

PMID- 19867434
TI  - STUDIES IN ISOAGGLUTINATION : II. THE OCCURRENCE OF GROUPED ISOAGGLUTINATION IN
      THE LOWER ANIMALS.
AB  - Grouped isoagglutination is not limited to man, but is much more widespread than
      has been hitherto suspected. It occurs in the bloods of steers and rabbits. It
      seems probable that it will be found to occur in the bloods of other animals.
      Just how many of the isoagglutinins and the isoagglutinable substances in
      different species are respectively identical is still to be determined. The work
      is being continued with other animals.

PMID- 19867435
TI  - STUDIES IN ISOAGGLUTINATION : III. TONICITY IN ISOHEMAGGLUTINATION.

PMID- 19867436
TI  - THE DISTRIBUTION OF SOLUTIONS IN CARDIECTOMIZED FROGS.
AB  - Strychnin and adrenalin when injected into cardiectomized frogs are efficiently
      distributed all over the animal body and when administered in sufficient
      quantities produce the usual reactions of these alkaloids. The experiments with
      strychnin prove positively that the paralysing effect of this poison is due to
      its direct action upon the nerve cells of the cord, and not, as Verworn assumes,
      to a paralysing action upon the heart. When morphin is injected into
      cardiectomized frogs the effects are much greater and incomparably more rapid
      than when administered to a normal frog. The normal circulation probably contains
      substances derived from some organs capable of modifying and retarding the
      specific effects of morphin. The distribution of solutions in animals deprived of
      their circulatory apparatus takes place through the tissue spaces, which present
      a more or less well connected system of communications throughout the entire
      animal body, especially through its peripheral parts. This mode of distribution
      is designated as the peripheral mechanism. In contrast to the centralizing
      cardiovascular apparatus, the peripheral mechanism permits a greater autonomous
      action of organs and a more localising effect of injections. The peripheral
      mechanism found to be active in animals deprived of their circulation is probably
      identical with the mechanism which serves for distribution of the mesolymph in
      living animals not yet possessing a circulatory apparatus. The existence of the
      peripheral mechanism in animals with a cardiovascular apparatus possesses
      probably a phylogenetic significance. It is assumed that the activity of the
      peripheral mechanism is probably not completely suppressed even in the presence
      of a normally acting circulatory apparatus; that it exerts a greater
      physiological influence in parts in which the circulation is normally some-what
      difficult; and that it unfolds an activity in pathological conditions in which
      the circulation has been eliminated or reduced in some parts of the body, or in
      which the energy of the entire circulation has been reduced.

PMID- 19867437
TI  - THE INFLUENCE OF DISTILLED WATER ON THE HEALING OF SKIN WOUNDS IN THE FROG.

PMID- 19867438
TI  - ON THE PHYSICOCHEMICAL REGULATION OF THE GROWTH OF TISSUES : THE EFFECTS OF THE
      DILUTION OF THE MEDIUM ON THE GROWTH OF THE SPLEEN.
AB  - It may be concluded that the degree of dilution of the culture medium has a
      marked influence on the rate of growth of splenic tissue. The maximum
      acceleration was obtained in a medium composed of three volumes of normal plasma
      and two volumes of distilled water. The growth in this hypotonic plasma was very
      much larger than in normal plasma. On the contrary, the growth of the spleen in
      hypertonic plasma was always less than in normal plasma. In other experiments, we
      found that in diluted plasma there was also an acceleration of the growth of the
      skin, the heart, and the liver of chickens. The skin of adult frogs also grew
      more actively in this plasma. The optimum degree of dilution varied according to
      the nature of the tissues and to the species of the animals. While the plasma
      containing two fifths distilled water produced the largest growth of splenic
      tissue, a slightly less diluted medium was more favorable for the liver and the
      heart, and generally for the skin also. The action of hypertonic plasma varied
      also in a large measure. While the spleen did not grow at all in the medium
      containing 0.0124 and 0.0144 sodium chlorid, the skin, on the other hand, could
      stand a high concentration of the sodium chlorid. Even its growth was activated
      in media containing 0.0094 and 0.0124 sodium chlorid and was greater than with
      normal plasma. The spleen of kittens was very easily affected by the changes of
      the dilution of the plasma, while the skin of the frog presented its best growth
      in plasma containing one half distilled water. Marked variations in the
      sensitiveness of tissues to hypertonic and hypotonic media will probably be
      observed in animals of different species. From these experiments, three
      conclusions can be drawn: namely, that certain laws of growth, discovered by
      Loeb, in lower organisms are true also for higher organisms; that normal plasma
      is not the optimum medium for the growth of tissue; and that each tissue has
      probably its optimum medium. The growth of the spleen is, without doubt,
      considerably modified by the variations of the dilution and perhaps of the
      osmotic tension of the plasma. It is possible then that the influence of osmotic
      tension, discovered by Loeb, in the growth of certain organisms, is a general law
      applicable as well to higher forms of life- frogs, cats, and chickens-as to lower
      organisms-tubularia and sea-urchins. In placing tubularia in different dilutions
      of sea-water and distilled water, Loeb found that the greatest rate of
      regeneration was observed when two volumes of distilled water were added to three
      volumes of sea-water. But fertilized eggs of sea-urchins were more sensitive to
      the action of hypertonic plasma, and they all died in a dilution of sea-water
      with two fifths distilled water. If only one fifth distilled water was added to
      the sea-water they developed normally. We found that the cells of certain tissues
      of the chicken follow a similar rule, since the maximal growth of the spleen is
      obtained in plasma containing two fifths distilled water, while other tissues
      grow better in a less hypotonic medium. Normal plasma is certainly not the ideal
      medium for the growth of tissues, since slight modifications of the tension, the
      alkalinity, or the addition of certain inorganic salts to normal plasma, increase
      the rate of the growth of tissues.

PMID- 19867439
TI  - CULTIVATION IN VITRO OF MALIGNANT TUMORS.

PMID- 19867440
TI  - THE BEHAVIOR OF BACILLUS LEPRAE IN COLD-BLOODED ANIMALS.
AB  - Before proceeding to a discussion of the experiments upon cold-blooded animals,
      it is necessary to review briefly some of the work recently done with the
      bacillus of leprosy. The appearance of the bacillus in man and its behavior under
      artificial cultivation, and in the tissues of lower animals, should be considered
      in order that comparisons may be drawn. In their studies with the organism under
      cultivation, Duval and Gurd pointed out that the long, slender, and beaded
      appearance of the leprosy bacillus described by Hansen, in 1872, is lost when
      removed for several generations from the parent stem, and under artificial
      cultivation the organism becomes unbeaded, short, and coccoid. Duval also noted
      that these changes in morphology were always followed by rapid multiplication of
      the organism. Duval argues, a priori, that the bacillus is not in a favorable
      environment in the human tissues. If these deductions are correct, the morphology
      of the leprosy bacillus should vary according to the resistance offered by the
      tissues of different animals. The resistance of the human host to the leprosy
      bacillus becomes more evident in the light of the clinical aspect of the disease.
      The long period of incubation, the duration of the disease, and the disappearance
      of the bacilli preceding the healing of the infected foci show that the
      resistance offered to the bacillus by the human tissues is not to be
      overestimated. This opinion is confirmed when the behavior of the leprosy
      bacillus under cultivation and in the tissues of various mammals is compared.
      When cats, rabbits, bats, guinea pigs, and rats are inoculated either below the
      skin or into the peritoneal cavity with large quantities of Bacillus leprae, a
      slight local reaction follows within twenty-four to forty-eight hours, but no
      definite lesions are produced and the bacilli soon disappear. The resistance of
      some animals to Bacillus leprae is well illustrated by two cats which were
      inoculated subcutaneously and intraperitoneally with a heavy suspension of
      Bacillus leprae. These animals were killed and examined three days later, but the
      bacilli were not demonstrable from the regions about the sites of inoculation.
      Pigeons are likewise refractory. It is impossible to cause a local reaction in
      these birds, and the injected bacilli disappear rapidly. Hence, probably no
      multiplication takes place in them. Goats, young pigs, and white and dancing mice
      are in a degree susceptible to injections, and though undoubted lesions are
      produced, and multiplication of the bacilli occurs, the lesions and bacilli
      disappear after a limited time. Acid-fast bacilli which are recovered from the
      lesions are long, slim, and beaded, though the organisms used in the inoculations
      were short, unbeaded, and coccoid. Monkeys inoculated with cultures of the short
      unbeaded forms react promptly. The lesions resulting, though confined in most
      instances to the site of inoculation, occasionally appear at distant points. The
      number of bacilli present in the nodules and their arrangement within typical
      lepra cells show that multiplication has taken place. The organism has, however,
      changed from the short coccoid form to the long, slender, beaded form. Though the
      lesions induced and the bacilli present are in every way similar to those found
      in man, their tendency to disappear gradually after a quiescent stage clearly
      denotes that the tissues of the monkey, although less refractory than the tissues
      of the animals previously mentioned, still offer resistance to invasion. While
      mammals react but poorly to inoculations of the leprosy bacillus, this reaction
      manifests itself in various ways in different species. For example, while
      multiplication of the organism with the production of lesions occurs in some
      species, in others that are more refractory, the injected bacilli assume the
      involuted or beaded forms and do not multiply or produce lesions; in others,
      still more resistant to the action of the leprosy bacillus, the organisms quickly
      undergo granular metamorphosis and disappear. Furthermore, in some species the
      lesions are, in most instances, limited to the site of inoculation, and though
      presenting all the characteristics of the lesion in man, the nodules and the
      bacilli disappear after a variable time. This behavior of the leprosy bacillus
      can be accounted for only by the degree of resistance offered by the tissues of
      the individual host. Since the morphology of the organism invariably changes from
      the short coccoid to the large beaded form when placed in insusceptible animals,
      and conversely, from the long beaded forms to the short coccoid forms when placed
      in susceptible animals, the deduction can be drawn that the organism varies in
      morphology and rapidity of growth according to the susceptibility of the host.
      Examples of similar behavior of Bacillus leprae in the human subject are known to
      all investigators of leprosy. Ulcers and nodular areas often heal, and the
      bacilli disappear with little or no treatment. It is true that while older
      lesions are healing, new ones are constantly appearing, yet the duration of the
      disease and its undoubted tendency towards healing shows that conditions in the
      human subject are variable, and suggests that the organism has its natural
      habitat in some other host. The experiments presented here serve to show that the
      bacillus of leprosy meets but little or no resistance in the tissues of cold
      blooded animals, multiplies in their tissues, and may be harbored by them without
      apparent discomfort or external evidence of the disease. That no appreciable
      resistance is offered to the multiplication of the leprosy bacillus by many
      species of cold-blooded animals is shown by the fact that aside from the trauma
      produced by the inoculation and the slight initial reaction of the tissues, the
      organism continues to grow profusely, and to invade the tissues without further
      reaction. Quite the opposite condition occurs in mammals: in some of these the
      leprosy bacillus degenerates into a granular mass shortly after inoculation; in
      others that are less refractory, typical lesions appear, but they seldom extend
      from the point of inoculation; and while the bacilli multiply slowly, they do not
      infiltrate the tissues, but disappear after a short time, the lesions healing.
      That multiplication of Bacillus leprae occurs in the tissues of cold-blooded
      animals is shown by the fact that while animals examined a few days after
      inoculation show but a few scattered organisms, those killed at longer intervals
      show a proportional increase in the number of bacilli. Furthermore, the few
      bacilli found at the early-period are extracellular and scattered, while after
      longer periods they tend to be massed and enclosed in large lepra cells. The
      supposition that these lepra cells are phagocytes has naturally arisen. Duval
      holds that they are not phagocytes in the true sense of the term, that the
      bacilli penetrate the cells rather than that the cells engulf them, after which,
      finding conditions for growth favorable, they multiply without causing serious
      injury to the cell. The size of the cell depends upon the size of the colony
      within. The experimental work bears out this view since the decrease in number of
      the organisms observed in animals killed shortly after inoculation depends not
      upon phagocytic action nor upon cells which appear later when active lesions are
      established. In early lesions, the lepra cells are smaller, barely measuring
      twenty to thirty microns in diameter, and contain but few bacilli; whereas in
      older ones, they attain a diameter of 100 microns or even more, and contain
      enormous numbers of bacilli. Were this increase in size due to phagocytic action,
      some cells would be found in which the limit of their capacity had been reached;
      and they would either contain a mass of dead and disintegrated bacteria or would
      themselves show evidence of disintegration. On the contrary, the bacilli, though
      they occupy most of the cell, show no signs of disintegration, and the nucleus
      and the cytoplasm of the cell retain normal staining properties. That the
      invasion and multiplication of the bacilli cause an irritation is evident by the
      amitotic divisions of the nucleus which occur in the larger cells. The absence of
      external evidence of invasion by Bacillus leprae in cold-blooded animals, and the
      apparent lack of discomfort caused by the presence of the organism within their
      tissues, are points which should be remembered in considering the sources from
      which leprosy may be transmitted. In not a single instance in the numerous
      experiments presented here would it have been possible, from any external sign,
      to suspect that the animals were harboring multitudes of leprosy bacilli. While
      the evidence in support of the opinion that leprosy may be transmitted from man
      to man appears sufficiently strong to warrant this belief, the number of cases in
      which infection can be actually traced to this source is small. Since leprosy is
      known to be prevalent where fish and sea-food are plentiful, and since the
      experiments here recorded prove that fish can be infected by being fed cultures
      of Bacillus leprae, or nodules from human lepers, or bits of fish previously
      infected with the leprosy organism, account should be taken of the possibility
      that leprosy, in certain localities, may arise from this source of infection. The
      question as to how and from what source leprosy bacilli enter the human body may
      be still regarded as an open one. Isolated examples of direct infection of
      healthy human beings from lepers have been reported by Arning and Nonne, by
      Manson, and others. The notion that the agency of infection is already infected
      human beings, that is lepers, is at the foundation of the modern practice of the
      isolation and segregation of lepers, which would seem to have brought about a
      definite decrease in the prevalence of the disease. (ABSTRACT TRUNCATED)

PMID- 19867441
TI  - COMPLEMENTOID AND THE RESISTANCE OF THE MID-PIECE OF COMPLEMENT.

PMID- 19867442
TI  - CONCERNING ADENOMATA ORIGINATING FROM THE ISLANDS OF LANGERHANS.
AB  - Small encapsulated tumors of the size of peas, or even smaller, are occasionally
      found in the pancreas. These tumors are benign, and have a structure similar in
      all respects to that of an hypertrophied island of Langerhans. The distinctions
      between adenomata and forms of regenerative hypertrophy, sometimes so difficult
      to make in the breast, prostate, liver, and other organs, is not easily drawn in
      the present case. The fact that one may encounter all gradations in the size of
      islands, from that of the normal island to that of the tumors, suggests that it
      is more reasonable to consider such tumors merely as hypertrophied islands rather
      than as adenomata originating from islands.

PMID- 19867443
TI  - THE RELATION OF THE REACTIVE STROMA FORMATION TO THE TRANSPLANTABILITY OF THE
      CANCERS OF THE WHITE RAT.

PMID- 19867444
TI  - THE MICROGRAPH : AN INSTRUMENT WHICH RECORDS THE MICROSCOPIC MOVEMENTS OF A
      DIAPHRAGM BY MEANS OF LIGHT INTERFERENCE, AND SOME RECORDS OF PHYSIOLOGICAL
      EVENTS SHOWING THE REGISTRATION OF SOUND WAVES INCLUDING THE HUMAN VOICE.

PMID- 19867445
TI  - AN EXPERIMENTAL STUDY OF THE QUESTION OF ASPIRATION OF FOREIGN MATERIAL INTO THE
      AIR PASSAGES DURING INTRATRACHEAL INSUFFLATION.
AB  - The foregoing experiments clearly justify the following conclusions :-
      Intratracheal insufflation protects the respiratory tract very efficiently
      against any invasion from the pharynx. The filling up of the pharynx with
      extraneous material, whether it be from the stomach or from the mouth, brings no
      danger to the trachea and bronchi. This holds true even if the animal is under
      deep anesthesia. On the other hand, the presence of a tube in the trachea or
      larynx without the protection of an effective recurrent air stream, definitely
      facilitates the entrance of foreign material from the pharynx into the trachea.
      Anesthesia, which removes the protective action of deglutition, greatly increases
      the danger from aspiration in these cases.

PMID- 19867446
TI  - A FEW OBSERVATIONS ON THE ACTION OF SALVARSAN UPON THE IRRITABILITY OF NERVE AND
      MUSCLE.
AB  - These experiments have shown that salvarsan is a comparatively inactive drug when
      applied directly to nerve and muscle tissue of the frog. In perfusion experiments
      with alkaline solutions, no detrimental action whatever was to be seen either
      upon direct or indirect irritability. In bathing .experiments, in which the
      concentration of the salvarsan in the various solutions was surely much higher
      than that in which it reaches the peripheral tissues in the human subject through
      the circulation, the loss of irritability occurred only after a long period of
      exposure to the drug.

PMID- 19867447
TI  - THE BACTERIOLOGY OF SPUTUM IN COMMON NON-TUBERCULOUS INFECTIONS OF THE UPPER AND
      LOWER RESPIRATORY TRACTS, WITH SPECIAL REFERENCE TO LOBAR AND BRONCHO-PNEUMONIA.
AB  - 1. In our examinations, only 38 per cent. of the infections of the respiratory
      tract below the glottis were pure, and this percentage was reached only by
      carefully following Kitasato's method of handling sputa. 2. Lobar pneumonia may
      produce sputum free from pneumococci, and may undoubtedly be caused by organisms
      other than thepneumococcus. 3. There is found a marked yearly variation in the
      organisms which excite inflammation of the respiratory tract. 4. Micrococcus
      catarrhalis is usually considered a common secondary invader; but it may, and
      probably frequently does, assume pathogenic properties.

PMID- 19867448
TI  - THE RESISTANCE OF THE END-PIECE AND MID-PIECE OF COMPLEMENT INACTIVATED BY
      DISTILLED WATER.

PMID- 19867449
TI  - STRONGYLOIDES INFECTIONS IN MAN AND ANIMALS IN THE ISTHMIAN CANAL ZONE.
AB  - From a study of strongyloides infections in man and animals in this region, it
      has been determined, in confirmation of the view of Grassi, Calmette, and others,
      that they are not causative factors in the production of diarrhea. The mother
      worm, however, burrows into the mucosa and deposits her ova there. Certain tissue
      reactions take place and are evidenced by the cellular proliferation in those
      portions of the intestines occupied by the nematodes. In animals, there is an
      associated anemia, not positively attributable to the strongyloides, but, on the
      other hand, not attributable to any other cause. It is possible that S.
      stercoralis may cause some degree of anemia in man. The amount is indeterminable
      in this region among hospital cases on account of the associated hookworm disease
      or malaria. Portals of entry for various microorganisms are made by the female
      mother worm and her larvae in the small intestine, and, while no case of general
      bacterial infection has been proved to have arisen in this way, its occurrence is
      possible and highly probable. In the cultures of strongyloides of man, there is
      among natives, who presumably are infected with purely tropical strains, a very
      marked predominance of development by the indirect or sexually differentiated
      mode, in some cases, an absolutely pure culture of the indirect mode larvae being
      obtained. There are, however, natives, cultures from whose stools contain from a
      single filariform larva of the direct phase up to a very definite predominance of
      this mode. Cultures from natives of the temperate zones contain a marked
      predominance of the direct phase larvae. The presence of the filariform (direct
      mode), larva is perhaps best accounted for by its being an attempt at more
      perfect parasitism (Stiles). From a correlation of culture study with the results
      of a histological examination of the invaded mucosa, this explanation of the
      derivation of the two phases is suggested. The mother worm in the intestinal
      tract has two kinds of progeny: (a) those expelled into the crypts or lumen, and
      (b) those imbedded in the intestinal wall. One lot becomes larvae of either the
      direct or indirect phase; the other lot of the opposite phase. It appears to me
      that the intraepithelial cell-developed larvae furnish the direct phase, while
      the embryos expelled directly from the mother become the indirect phase larvae.
      This will require for its confirmation a study of cultures in connection with a
      histological examination of the infected intestinal wall. Cold merely inhibits
      the development of the larvgammaaelig; into either the filariform (direct) or
      into the sexually differentiated adults, and does not alter the anlage. The
      resistant as well as the infecting form is the filariform larva, and all chemical
      larvicides must be directed against this form. Thymol and an alkaline cresol
      resin soap were found to be effective larvicides for the filariform larvae. Two
      new strongyloides of the monkey and ant bear are described. Cultures of these
      nematodes show a predominance of the indirect mode of development.

PMID- 19867450
TI  - ON THE TOXIC ACTION OF CERTAIN NORMAL SERA AND ITS RELATION TO ANAPHYLAXIS.

PMID- 19867451
TI  - STUDIES IN IMMUNITY AND ANAPHYLAXIS : THE PROTEINS OF THE KIDNEY AND LIVER.
AB  - 1. The sera of rabbits injected repeatedly with the nucleoproteins, globulins,
      and albumins of the liver and kidney of the dog give no evidence in vitro or in
      vivo experiments of organ affinity. The precipitin test offers no proof of the
      specificity of these sera for the proteins employed as antigens. 2. The
      anaphylaxis reaction applied to the same proteins indicates a slight relative
      organ affinity but no specificity as far as the respective protein fractions are
      concerned. The relative organ affinity resides, rather, in the globulin and
      albumin fractions than in the nucleoprotein fraction. Dog serum used both as a
      sensitizing and an intoxicating agent gives rise to very active cross reactions
      with organ proteins, thus failing to support the theory of organ or of protein
      specificity. 3. These results do not support the view put forward that
      nucleoproteins play an important part in the course of production of cytotoxic
      immune sera.

PMID- 19867452
TI  - CALCIUM AND IRON INCRUSTATION AND OTHER LESIONS OF THE ELASTIC TISSUE OF THE
      SPLEEN AND LIVER.
AB  - In conclusion, it may be said that the lesion described consists of a selective
      impregnation of the elastic tissue in the splenic trabeculae and vessels with the
      phosphates-and perhaps other salts-of calcium and iron. There is a further
      chemical change in the elastic fibers which may be expressed by the term
      "elacin." Degenerated and, especially, calcified elastic tissue-even more than
      calcification in general-seems to possess an affinity for iron salts. The iron
      incrustations occur principally in congested or hemorrhagic tissues. The
      etiological agent in this case is obscure. The only other example of this lesion
      in the spleen was in a case of Banti's disease. Many features of this case
      suggest a primary splenomegaly, but the evidence in its favor is not conclusive.
      Calcified elastic fibers, without the iron and elacin reactions, were also
      present in the liver, which was the seat of a recent, apparently biliary or
      infectious, cirrhosis. The elastic tissue of other organs showed nothing
      remarkable except in the skin, where the fibers were undergoing the usual senile
      changes.

PMID- 19867453
TI  - SERUM TREATMENT OF INFLUENZAL MENINGITIS.
AB  - The injection of virulent cultures of Bacillus influenzae into the subdural space
      of several species of lower monkeys is followed by the development of an acute
      inflammation of the meninges, corresponding in clinical, bacteriological, and
      pathological effects with influenzal cerebrospinal meningitis in human beings.
      Experimental influenzal meningitis in the monkey is a lethal disease which
      terminates fatally in from thirty-six hours to four days after the inoculation.
      The injected influenza bacilli produce their effects through multiplication in
      the course of which they penetrate from the subdural space into the general blood
      current, from which they may be recovered during life and at autopsy, as is also
      true of the spontaneous form of influenzal meningitis in man. By repeated
      injection, over a period of many months, of living virulent cultures of Bacillus
      influenzae into the goat, an immune serum possessing moderate agglutinating and
      high opsonic power may be produced, which is capable, when injected into the
      subdural space, of arresting the progress of an experimental influenzal
      meningitis, and of bringing about recovery in monkeys thus affected. As a result
      of the serum injections, the influenza bacilli in the meninges are more freely
      englobed by phagocytes, their number is reduced, their capacity of growth
      diminished, and the eruption into the blood arrested. Along with these effects
      go, hand in hand, cessation of the local inflammatory process and progressive
      amelioration of the symptoms of illness, to be followed usually by rapid
      restoration of health. In view of the highly fatal character of influenzal
      meningitis in human beings, the employment of an immune serum by subdural
      injection is recommended. Undoubtedly it will be necessary to apply the serum
      early and by repeated injections, by means of lumbar puncture, to secure
      beneficial results. The early application will, in turn, be dependent upon prompt
      bacteriological diagnosis, which can be made, as a rule, by the immediate
      microscopical examination of the cerebrospinal fluid without the employment of
      cultural methods. When possible, the microscopical diagnosis should be confirmed
      by cultural tests.

PMID- 19867454
TI  - ON THE FORMATION OF PRECIPITATES AFTER THE INTRAVENOUS INJECTION OF SALVARSAN.
AB  - The results of these experiments are definite. There is, in the first place, a
      very striking difference with regard to precipitate formation between the acid
      and alkaline solutions of salvarsan when injected intravenously. Intravenous
      injections of alkaline solutions of salvarsan produce no precipitate in the
      blood, while injections of the acid solution nearly always give a precipitate.
      Furthermore, after injections of the acid solution, there is a striking
      difference between the blood from the right side of the heart and that from the
      left side. At the end of injections of an acid solution of salvarsan, a
      precipitate was seldom present in the arterial blood. Blood taken from the left
      ventricle at this time (at autopsy) also showed no precipitate in a large
      majority of cases; in eight experiments there was no precipitate, in three a
      doubtful trace of precipitate, and in one a definite small amount. On the other
      hand, blood obtained from the right ventricle and the lungs showed a very
      different condition. In ten out of twelve animals (rabbits and dogs), blood from
      the right ventricle contained a definite precipitate, and in a number of these
      cases the amount of precipitate was large. Blood squeezed from the lungs showed
      in eight out of ten cases at least as much precipitate as was found in the blood
      from the right ventricle. The results of injections of alkaline solutions of
      salvarsan, as pointed out before, are quite different from those produced by the
      acid solutions. In thirteen experiments upon dogs and rabbits, no trace of a
      precipitate was found in the arterial blood, the blood from the left ventricle,
      the right ventricle, or the lungs. There is no apparent difference in the process
      of precipitate formation whether salvarsan solutions and the blood are mixed in
      vivo or in vitro. In both mixtures the acid solutions produce a precipitate,
      while the alkaline solutions of salvarsan do not. These experiments have
      demonstrated the fact that a precipitate is present in the blood after an
      injection of an acid solution of salvarsan. One would expect that such a
      precipitate, consisting as it usually does of rather coarse particles, would, if
      brought to the medulla, cause immediate death by producing emboli. However, the
      freedom from such occurrences may be explained by the fact that the precipitate,
      which is abundantly present in the right ventricle, is only rarely seen in blood
      taken from the carotid or femoral arteries or even from the left ventricle
      itself. The fact itself, however, is quite difficult to interpret. It might
      perhaps be assumed that the precipitate is filtered out during its passage
      through the lung capillaries. If this is the case, we might expect intravenous
      injections of salvarsan to produce embolism in the pulmonary vessels with
      consequent fatal results. As a matter of fact, we have in the recent literature
      an instance which seems to point to such a result. Miessner (6) tried the effects
      of salvarsan in cattle which had foot and mouth disease. He used at first the
      acid solution, and though the dose was small, seven milligrams per kilo of body
      weight, all the animals (four) died in from ten hours to two days after the
      injection. They all showed labored respiration during or soon after the injection
      of salvarsan. He then decreased the dose to five milligrams per kilo of body
      weight, and repeated the experiments. He used also normal animals as controls
      upon those which had the foot and mouth disease. Both the sick and normal
      (control) animals showed labored respiration. One died after four days. At
      autopsy all organs except the lungs appeared to be normal. The lungs presented
      the following appearance: There were grayish yellow spots scattered irregularly
      over the surface. On the cut surface these were seen as grayish yellow spots the
      size of a pea, which appeared in groups and which sometimes filled a lobule
      completely. Other spots were surrounded by a small area of dark red lung
      parenchyma. The affected portion contained no air and felt solid. In adjacent
      parts the tissue seemed normal. A microscopic examination showed that the larger
      and smaller pulmonary arteries were filled with uniform, homogeneous, yellow
      masses. About the vessels there was a serous exudate. In brief, the changes seen
      indicated, he believed, that there was a thrombosis of the blood-vessels with
      inflammatory exudative changes of the lung parenchyma. Miessner states that a
      similar pathological condition was found in a normal control animal that died. He
      suggests that the acid solution of salvarsan might lead in man to a thrombosis of
      the pulmonary arteries. In support of this suggestion, he mentions a case
      reported to him by Ehrlich of a man who died following the injection of an acid
      solution. The lung picture in this case was somewhat similar to that which he had
      found in cattle. It may be mentioned in passing that Miessner found that alkaline
      solutions of salvarsan were far less toxic than the acid solutions. Animals
      (cattle) which received in an alkaline solution 400 milligrams of salvarsan per
      kilo of body weight did not show the least symptom of disturbance. In contrast to
      Miessner's results seem to stand my observations and those of Auer described in
      the introduction of this paper. Auer (5) found (in 8 rabbits) that no evident
      harmful effects followed the injections of very large doses of the acid solution,
      if they were given in a highly diluted form (one tenth per cent.). In my own
      experiments, it was found that a one fifth per cent. acid solution (3 rabbits)
      and even a one half per cent. solution (1 rabbit) produced no ill effects. The
      experiments described in this paper make it certain that the doses of the acid
      solution given to these last mentioned four animals must have produced a
      precipitate in the right ventricle and in the lungs, and yet the animals survived
      and showed no symptoms whatever of disturbance following the injection. This
      difference between our observations and those of Miessner might perhaps be
      explained by the assumption that the action of salvarsan in acid solution is more
      deleterious to cattle than to rabbits. Furthermore, Miessner seems to have
      injected the salvarsan in high concentrations. In one instance, in which figures
      are given, the drug was administered in a five per cent. solution. As mentioned
      before, Auer has shown the importance of the concentration. While in a one tenth
      per cent. solution twenty and thirty milligrams per kilo of body weight of the
      acid solution may be injected with impunity, even six or seven milligrams per
      kilo may prove rapidly fatal when injected in a one half per cent. solution. Our
      own results, however, leave us with two puzzling questions : First, if the acid
      solution of salvarsan causes such a coarse precipitate in the right ventricle and
      in the lungs, how does it happen that this precipitate does not bring about the
      death of the animal? Second, what is the real cause of the remarkable fact that
      this precipitate does not pass over into the arterial side of the circulation?
      Does the precipitate undergo a profound chemical or mechanical change while it
      passes through the lung capillaries? In future investigations we may try to
      answer these interesting questions. For the present, it is necessary to be
      content with the establishment of the bare facts as they are presented in the
      conclusions.

PMID- 19867455
TI  - PHAGOCYTIC IMMUNITY IN PNEUMOCOCCUS INFECTIONS, AND IN PNEUMONIA WITH RELATION TO
      THE CRISIS.
AB  - These results seem definitely to show, through animal experiments, that
      phagocytic immunity is to a high degree specific for the organism used in
      immunization, and that the amount of opsonin produced in the process depends to a
      great extent on the virulence of the organism. The negative results obtained with
      post-critical sera do not mean that opsonins may not be present (our five
      positive cases indicate their presence), but they emphasize strongly the fact
      that they are not formed to any great extent. Therefore this study adds further
      support to the view that although opsonic immunity is produced in pneumonia, it
      is not the only means of defense possessed by the body, and by itself it cannot
      explain the crisis.

PMID- 19867456
TI  - INFECTION OF RABBITS WITH THE VIRUS OF POLIOMYELITIS.

PMID- 19867458
TI  - PATCHING OF THE ABDOMINAL AORTA WITH A PIECE OF RUBBER.

PMID- 19867457
TI  - THE ULTIMATE RESULT OF A DOUBLE NEPHRECTOMY AND THE REPLANTATION OF ONE KIDNEY.

PMID- 19867459
TI  - THE CULTIVATION OF TISSUE IN PLASMA FROM ALIEN SPECIES.
AB  - 1. Rat sarcoma may be cultivated in mouse plasma and guinea pig plasma, and the
      growth differs only in extent from that observed in rat plasma. The cells may
      show active wandering in guinea pig plasma after thirty days, if transferred at
      proper intervals to fresh medium. 2. Rabbit plasma is less suitable than that of
      guinea pigs and mice for the growth of rat sarcoma; growth is slow, but it may
      continue for twelve days. 3. The duration of growth of rat sarcoma in dog plasma
      is from two to three days. 4. The duration of the growth of rat sarcoma in pigeon
      plasma is four to five days. Transferring the tissue to fresh pigeon plasma does
      not lengthen the period of activity. 5. No growth whatever is observed of mouse
      and rat tissues in goat plasma. Studies of the fate of the cells indicate the
      presence in goat serum of a substance toxic for these tissues. 6. In preparations
      of rat sarcoma in human plasma, liquefaction of fibrin is regularly observed. The
      phenomena of growth consist in an outwandering of cells along the cover glass,
      and, after four to six days, the formation of giant cells. Such giant cells are
      produced in larger number in the cultivation of rat spleen. 7. The degree of
      suitability of the different kinds of alien plasma used as culture media for
      mouse and rat tissues does not go hand in hand with the closeness of relationship
      of the species. 8. Rat spleen may be cultivated as readily in foreign plasma as
      the virulent transplantable tumors.

PMID- 19867460
TI  - STUDIES ON IMMUNITY IN CANCERS OF THE WHITE RAT : THE SIGNIFICANCE OF "THE
      SPECIFIC STROMA REACTION.".

PMID- 19867461
TI  - ON THE MECHANISM OF THE FORMATION OF METASTASES IN MALIGNANT TUMORS : AN
      EXPERIMENTAL STUDY.

PMID- 19867462
TI  - THE FORMATION OF PRECIPITATES IN THE BLOOD IN VITRO BY ACID SALVARSAN SOLUTIONS.

PMID- 19867463
TI  - EXPERIMENTAL IMMUNITY WITH REFERENCE TO THE BACILLUS OF LEPROSY : PART I. A STUDY
      OF THE FACTORS DETERMINING INFECTION IN ANIMALS.
AB  - Repeated experiments have proven that few, if any, of the ordinary laboratory and
      domestic animals are immune against infection by Bacillus leprae. As previously
      reported, the goat, horse, guinea pig, and many cold-blooded animals (Couret)
      have been found susceptible to invasion by this organism. Two factors are of
      great importance in effecting infection. In the first place, a sufficiently large
      number of organisms must be employed, and, what is still more important, second
      and subsequent inoculations are more liable to produce leprous lesions than are
      primary injections. Moderate doses used in the first inoculation of animals are
      comparatively harmless as regards their ability to induce lesions. Such
      preliminary doses, whether they consist of living or dead organisms, produce a
      condition of hypersensitiveness or allergy, which renders it possible by a second
      injection of viable bacilli to induce the development of a reactionary lesion.
      Lesions arising as the result of a second inoculation develop more rapidly,
      increase in size more quickly, and persist for a longer period than those taking
      place as the result of a single inoculation, even though very large doses are
      used. Moreover, the bacilli in these lesions are more liable to lead to
      metastasis and to a generalized infection. We regard the results of these
      experiments as having considerable bearing upon the development of the disease in
      human cases, since we find that it is chiefly among those living in prolonged
      intimate contact with leprous patients that leprosy develops. The proper
      interpretation of these findings is difficult and becomes, apparently, more
      complex the longer they are studied. We are accustomed to similar phenomena of
      anaphylaxis or allergy with protein materials and with certain bacteria,
      especially the tubercle bacillus. It is not surprising that a specific allergy or
      altered reaction should take place in animals previously injected with leprosy
      bacilli, either alive or dead; why, however, lesions should develop in which the
      bacilli continue to grow in animals which had recovered from previous injections,
      or the serum of which showed bactericidal properties and contained other specific
      antibodies, is not so easily understood. It is unnecessary in this paper to
      discuss the relative value of the different theories brought forward to explain
      the phenomenon of anaphylaxis. It must, nevertheless, be assumed that either as
      the result of the splitting of certain essentially non-toxic substances in the
      bacillus by specific ferment-like substances in the blood, which increase after a
      sensitizing dose, or by the joining of some body in the serum with certain
      substances in the bacilli, a toxic body is produced. Following the setting free
      or development of these injurious bodies, there results a cellular reaction, an
      area of local necrosis followed usually by the appearance of cells of the
      lymphoid and epithelioid type, and, especially if dead bacilli are used, by
      polymorphonuclear leucocytes. Such a reaction is usual in all allergic or
      anaphylactic conditions; but why the reaction should pre-dispose to the more or
      less permanent development of parasitic powers on the part of the bacilli is not
      so plain. The idea has been expressed by us, as the result of observations based
      chiefly upon the study of the changes in the tissues of human leprosy, that the
      presence of bacilli within the large multinucleated cells that are characteristic
      of the lesion is the result of active multiplication of the bacilli in these
      cells rather than of phagocytosis by the cells, although it is possible that
      their original entrance may be the result of phagocytic action. If this be the
      case, it is possible that, through the cellular reaction plus the necrosis of
      certain of the fixed tissue cells, a pabulum of split protein products results
      upon which the bacilli feed, and in which they find protection from the
      antibodies present in the blood serum. In our attempts to induce infection in
      various mammalian species with cultures of human leprosy, positive results have
      been obtained in almost every instance after the second injection of large
      numbers of the organism. In this manner, we have been successful in the
      production of lesions in the monkey, goat, horse, guinea pig, and mouse. The
      results of these experiments lead us to believe that the mechanism through which
      invasion and multiplication follows in these lower animals is similar to if not
      identical with that in man. A careful study of the progress of the disease in man
      together with the behavior of the organism in the monkey and the goat would
      suggest, at least, that the function of toxin production is, after all, of little
      use to the leprosy bacillus because it has seemingly acquired a highly parasitic
      existence; instead of which it is not only possible, but highly probable, that
      its defensive protection, whatever it may be, is enormously developed. After the
      inoculation of animals with either dead or living bacilli, the production of
      specific antibodies is induced; these do not develop in any considerable amount
      and apparently show no marked tendency to increase upon repeated injections. The
      tests of the sera in vitro indicate that the antisubstances are produced chiefly
      by the first few injections. Either the existence of some specific bacterial
      protective body, or what seems more probable, the protection afforded by the host
      cells in which the bacilli become ensconsed accounts, we believe, for the
      difficulty of producing in animals an antiserum of high potency. The idea, too,
      that the bacilli do not multiply to any great extent until they have entered
      certain cells of the host has, in a large measure, been verified by the
      artificial cultivation experiments. We know from our studies upon the biology of
      the organism that it will live for years in the most unfavorable conditions. This
      would suggest that during their sojourn in the tissue cells death as the result
      of autolysis rarely occurs, and as long as the cells can withstand the
      multiplication of the bacilli within and remain alive, so long are the bacilli
      protected from outside injurious influences, in consequence of which no
      disintegration of bacilli occurs to induce the production of immune bodies. On
      the other hand, death of the cells carrying the bacilli must occur from time to
      time, and this exposes large numbers of the organisms to the action of the body
      fluids, and, in consequence, to the condition of formation of specific
      antibodies.

PMID- 19867464
TI  - FURTHER OBSERVATIONS ON CERTAIN FEATURES OF EXPERIMENTAL SYPHILIS AND YAWS IN THE
      RABBIT.
AB  - 1. Lesions of the testicle and scrotum of the rabbit produced by the treponema of
      syphilis and of yaws afford material for the study of chemotherapy, of serum
      reactions, and of immunity. 2. On experimental and clinical grounds, it appears
      that yaws can be cured with a smaller dose of salvarsan than is necessary to cure
      syphilis. 3. The spirochaetae of syphilis do not become resistant after repeated
      treatments with salvarsan. 4. Sodium cacodylate has little effect on the
      treponema of either disease. 5. Mercury, in a single intravenous dose, has a
      spirillicidal effect, but the necessary dose usually causes the death of the
      animal later from nephritis. 6. Potassium iodid, in a single intravenous dose,
      has no spirillicidal effect. 7. The complement fixation reaction is closely
      correlated with the course of an infection, as is shown by its onset and its
      disappearance after castration or treatment. 8. Reinfection during the course of
      a testicular lesion does not occur, but it occurs after regression, treatment, or
      extirpation. 9. Specific differences between Treponema pallidum and Trepanema
      pertenue can be demonstrated in infected animals treated with salvarsan and
      reinoculated.

PMID- 19867465
TI  - METHOD FOR THE PURE CULTIVATION OF PATHOGENIC TREPONEMA PALLIDUM (SPIROCHAETA
      PALLIDA).
AB  - In conclusion, it may be pointed out that this is the first time that Treponema
      pallidum of Schaudinn has been proven beyond all doubt to have been obtained in
      pure culture. The method of cultivation described would appear also to be
      suitable for obtaining indefinite generations of the microorganism. Doubtless
      slight modifications will adapt it to a larger number of strains and possibly to
      the cultivation of all strains and to still other species of treponema. Finally,
      it may now be accepted as established that the testicular lesions produced in
      rabbits by means of syphilitic materials are the result of the multiplication of
      the pallida and not of some associated indefinite parasite.

PMID- 19867466
TI  - STUDIES WITH THE ELECTROCARDIOGRAPH ON THE ACTION OF THE VAGUS NERVE ON THE HUMAN
      HEART : I. THE EFFECT OF MECHANICAL STIMULATION OF THE VAGUS NERVE.
AB  - In hearts showing auricular fibrillation mechanical stimulation of the right
      vagus nerve causes, as a rule, marked slowing or stoppage of ventricular rhythm,
      without producing any appreciable effect in the electrocardiographic record of
      the auricular fibrillation. The ventricular pauses are apparently due to the
      blocking of stimuli from the auricles. The force of ventricular systole is
      distinctly weakened for several beats after vagus stimulation, and ectopic
      ventricular systoles have been seen in several instances, apparently the result
      of the vagus action. There may, in some cases, be lowered excitability of the
      ventricles, while no constant change is seen in the size of the electrical
      complexes representing ventricular systole.

PMID- 19867467
TI  - COMPLEMENT DEVIATION IN SCARLET FEVER WITH COMPARATIVE STUDIES OF THE WASSERMANN
      AND NOGUCHI SYSTEMS.
AB  - The Wassermann reaction in scarlet fever per se is uniformly negative. The
      antigen of scarlet fever liver yields practically the same results as that of
      luetic liver, and both fail to deviate complement with scarlet fever antibodies.
      The Noguchi reaction in scarlet fever is practically negative. Sixteen cases, or
      6.4 per cent. of 250 cases, were positive when active serum was used; with
      inactivated serum, but eleven, or 4.4 per cent., remained positive. Five of these
      eleven cases were also positive with the Wassermann system. In other words,
      sixteen cases, or 6.4 per cent., were positive according to the Noguchi system
      with active or inactivated serum or both, whereas with the Wassermann system only
      2 per cent. were positive. The presence of anti-sheep hemolysin normally in human
      serum is one of the main disturbing factors in the Wassermann system; for this
      reason, complement and hemolysin (made by immunization of rabbits) require
      careful titration. A positive Wassermann reaction usually indicates the presence
      of syphilitic antibodies, and a negative Noguchi reaction, their absence, and
      both systems should be used in the examination of all cases.

PMID- 19867468
TI  - AN ADDITION TO THE TECHNIQUE OF THE CULTIVATION OF TISSUES IN VITRO.

PMID- 19867469
TI  - THE EFFECT OF SALVARSAN UPON THE HEART IN DOGS.
AB  - The intravenous infusion of 0.5 per cent. acid "606" causes a weakening of the
      heart which is usually fatal. The intravenous infusion of 0.5 per cent. alkaline
      "606" causes no marked apparent effect upon the heart, but its factors of safety
      may be so reduced in some instances that a slight extra strain produces
      fibrillation and death.

PMID- 19867470
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON LOCALIZED INFECTIONS : THIRD PAPER: SOME FURTHER
      OBSERVATIONS UPON THE ACTION OF CERTAIN SOAPS ON THE PNEUMOCOCCUS AND ITS
      EXPERIMENTAL INFECTIONS.
AB  - In the test tube, sodium linoleate and sodium linolenate kill and dissolve
      virulent pneumococci more rapidly and in higher dilutions than sodium oleate;
      otherwise their action is the same. The intensity of action on the cocci is
      directly proportional to the degree of unsaturation of the acid. Blood serum
      inhibits the bacteriolytic and hemolytic action of unsaturated soaps partially or
      completely, according to definitive quantitative relations between serum and
      soap. Small quantities of serum completely inhibit the action of dilute soap
      solutions, but even whole serum does not prevent bacteriolysis and hemolysis by
      relatively concentrated soap solutions, i. e. 1 per cent. and 0.5 per cent. A
      given quantity of serum inhibits the action of the soaps in inverse ratio to
      their degree of unsaturation. The hemolytic and bacteriolytic action of soaps of
      the unsaturated fatty acids is probably due in part to their avidity for protein
      and not wholly to their ability to dissolve lipoids. Attempts to prevent serum
      inhibition of the lytic action of sodium linoleate and sodium linolenate were
      unsuccessful. The more unsaturated soaps are not as efficient in preventing fatal
      pneumococcic infection of animals as sodium oleate.

PMID- 19867471
TI  - THE RATE OF REGENERATION OF BLOOD PLATELETS.
AB  - By repeatedly withdrawing, defibrinating, and reinjecting blood, the platelet
      count in dogs can be reduced to an extremely low level. When the reduction in
      platelets and fibrinogen has been carried to an extreme degree the animals
      display a marked tendency to bleed. The regeneration of platelets after their
      removal by defibrination is remarkably rapid and amounts, on an average, to about
      one fifth of the entire number in the blood per day. From the experiments and
      from observations on the platelet count in human beings, it is believed that
      under the usual conditions of life platelets are utilized or destroyed and
      replaced in enormous numbers daily, and that the life cycle of the platelet is
      extremely short,-possibly a matter of a few days.

PMID- 19867472
TI  - THE EXCRETION OF DEXTROSE IN THE STOMACH AND THE SMALL INTESTINE.
AB  - The contents of the stomach and small intestine of normal rabbits, kept on a diet
      poor in easily convertible carbohydrates, when removed immediately after killing
      the animal (by clamping the trachea), usually contain a very small but measurable
      amount of dextrose (reducing substances). A preceding nephrectomy does not
      increase the amounts of the dextrose in these viscera. An intravenous injection
      of dextrose, if given in a sufficient quantity in a unit of time, causes a
      definite excretion, or increase of excretion, into the small intestine and the
      stomach. The amount of excretion, however, is incomparably smaller than the
      amount eliminated through the kidneys. A preceding double nephrectomy increases
      the gastro-intestinal elimination of the intravenously injected dextrose. The
      increase, however, is far too small to be considered in the light of a functional
      compensation for the loss of the considerable elimination through the kidneys.

PMID- 19867473
TI  - ON THE MECHANISM OF CHLORIN RETENTION IN PNEUMONIA.
AB  - THE FOLLOWING CONCLUSIONS MAY BE DRAWN FROM AN ANALYSIS OF THE PROTOCOLS: 1. The
      chlorin output is very much diminished during the process of experimental
      pneumonia in dogs (tables I and II). The quantity of chlorin retained in the
      cases with well developed exudates (table I) is much larger than the exudate
      could account for. 2. Turpentine pleurisy in dogs (tables III and IV) also is
      associated with a retention of chlorin, but this is not so marked as in
      pneumonia. There is no direct quantitative relation between the water output and
      the chlorin excretion. 3. The rabbits with pneumococcal septicemia (tables V and
      VI) did not retain chlorin in any phase of the disease, a fact which Hutchison
      has also noticed. It seems justifiable to conclude that the retention of chlorin
      in the organism in the course of pneumonia is conditioned by more than one
      factor. The formation of the exudate is one of these factors, but it alone is not
      capable of producing the same degree of chlorin retention as occurs in pneumonia.
      The additional factors are not yet determined; but it may be stated that the
      retention of chlorin is probably not due to the general effect of the
      pneumococcus on the organism or to its injury to the kidney. The principal cause
      of the retention seems, therefore, to be due to local changes associated with the
      pulmonary condition.

PMID- 19867474
TI  - ON THE COMPOSITION OF URINARY ALBUMIN.
AB  - A few findings which seem to be of importance may be pointed out:- Table I shows
      the analytical figures of serum-albumin, serum-globulin, and fibrin of the normal
      dog. The main difference between albumin and globulin appears in the relation of
      the precipitable to the non-precipitable total nitrogen and amino-nitrogen.
      Precipitable total nitrogen as well as amino-nitrogen is considerably larger in
      the albumin than in the globulin. In the cases of uranium nitrate nephritis
      (table II), the important figures approximate very closely those of normal serum
      albumin. The samples from dog 3, that had been poisoned at the same time with
      phosphorous oil and uranium nitrate, show relatively large variations as compared
      with the figures from specimens from the other dogs, chiefly as regards the amino
      nitrogen distribution: i. e., in dog 3, (1) the amount of amino-nitrogen to the
      total nitrogen in the solution before precipitation is higher; (2) the percentage
      of precipitable amino-nitrogen is larger; and (3) the ratio of precipitable amino
      nitrogen to precipitable total nitrogen exceeds that of the other cases. All
      these changes, together with the fact that the total precipitable nitrogen did
      not undergo any quantitative variation, suggest that in the case of dog 3 the
      analyzed material contained a higher amount of lysin or cystin. It may further be
      mentioned that the analytical figures in this case differ also from those of the
      normal serum-albumin and still more from those of the serum-globulin. These
      changes, however, were not found in the case of dog 4, although this animal was
      treated in the same manner as the preceding dog. In the cases of nephritis in man
      (table III), striking differences were met with in the case of acute scarlet
      fever nephritis (No. 1a) and in the case (No. 2) of a patient with chronic
      nephritis and Pott's disease. This patient died a few weeks after the specimen
      for analysis was collected. The autopsy showed a general amyloidosis. The
      variations in both cases consist in a lowering of the ratio of amino-nitrogen to
      total nitrogen in the solution before precipitation, and corresponding to this, a
      fall of the same ratio in the filterable nitrogen. Such a change points to a
      relatively larger amount of prolin and oxyprolin or tryptophan in these cases. As
      a whole, one may conclude that Van Slyke's method, carefully applied and
      sufficiently controlled, may also be used for the study of urinary albumin. The
      results already obtained indicate that definite differences in the composition of
      urinary "albumin" may be detected. As yet it is premature to establish a definite
      relationship between the chemical composition of the "albumin" and the clinical
      or pathological conditions under which it appears, but it seems hopeful that
      further work may lead to the finding of such a relationship.

PMID- 19867475
TI  - A PHYSIOLOGICAL STUDY OF EXPERIMENTAL NEPHRITIS DUE TO BACTERIAL POISONS AND
      CYTOTOXIC SERA.
AB  - The physiological study of experimental nephritis caused by poisons of bacterial
      origin demonstrates that the poisons may produce types of nephritis in which
      either vascular or tubular changes predominate. Diphtheria toxin produces a
      nephritis which in its late stage is of the vascular type, but in its early stage
      is distinctly tubular. Tuberculin and mallein uniformly cause lesions of the
      tubular type, which do not pass into the vascular type. Nephrotoxic and hemolytic
      immune sera cause changes in the kidneys which by physiological methods of
      observation present no evidence of vascular injury, but which are anatomically
      characterized by exudative glomerular lesions of moderate severity. This
      discrepancy between the results of anatomical and physiological study indicates
      that a lesion of the membrane controlling the passage of fluids may occur without
      alteration in the power of the vessels to contract and dilate. This fact is shown
      clearly by the lesion caused by hemolytic immune serum, which is in sharp
      contrast to the lesion caused by diphtheria toxin, since the latter substance not
      only alters the permeability of the membranes but also influences markedly the
      power of the vessels to contract and dilate. It is necessary therefore if the
      term "vascular" is used in its broadest sense, to recognize three types of
      vascular nephritis: (1) one in which little or no anatomical evidence of vascular
      injury is found, but in which physiological methods show profound vascular
      changes, as in arsenical nephritis; (2) one in which anatomical evidence of
      vascular (exudative) injury is prominent, but in which the physiological tests
      are negative, as in nephritis caused by a hemolytic immune serum; and (3) one in
      which both anatomical and physiological changes are prominent, as in diphtheria
      toxin nephritis.

PMID- 19867476
TI  - THE QUESTION OF ATHREPSIA.

PMID- 19867478
TI  - STUDIES OF THE PULMONARY CIRCULATION.

PMID- 19867477
TI  - NERVE FIBRILLAE IN THE PULMONARY ARTERY OF THE DOG.

PMID- 19867479
TI  - A STUDY OF SIMULTANEOUS TRACINGS FROM THE APEX OF THE HEART AND THE RADIAL ARTERY
      WITH THE MICROGRAPH.

PMID- 19867480
TI  - A STUDY OF TRACINGS FROM THE REGION NEAR THE APEX OF THE HEART.

PMID- 19867481
TI  - ON THE DISTRIBUTION AND DIRECTION OF MOTION OF THE INTERFERENCE BANDS OF LIGHT
      FORMED BY THIN PLATES AS THE THICKNESS OF THE PLATE VARIES.

PMID- 19867482
TI  - EXPERIMENTAL ACUTE NEPHRITIS: THE ELIMINATION OF NITROGEN AND CHLORIDES AS
      COMPARED WITH THAT OF PHENOLSULPHONEPHTHALEIN.
AB  - 1. Uranium and cantharidin, in the smallest doses capable of producing a distinct
      nephritis, tend to increase the elimination of nitrogen, probably by stimulating
      tissue katabolism. 2. Uranium, cantharidin, and potassium chromate, in larger
      doses, impair the power of the kidney to eliminate nitrogen; but this may not be
      evident unless the animal is on a high nitrogen diet, and the impairment, when
      due to potassium chromate, may not persist more than a day. 3. Small doses of
      uranium and of cantharidin cause a transient increase of chloride elimination
      which corresponds in a general way to the excess of diuresis. 4. Large doses of
      uranium and of chromate cause a fall, usually transient, in the chloride
      elimination. The chloride elimination may, however, be diminished forty per cent.
      for twenty-four hours without evidences of intoxication (vomiting). 5. The
      anatomic appearance of the kidney varies somewhat with the poison used and
      greatly with the period of survival after administration of the poison, but bears
      no definite relation to the nitrogen, chloride, or phenolsulphonephthalein
      elimination; marked anatomic alteration is compatible with normal elimination of
      all these substances and with freedom from symptoms of intoxication (vomiting).
      6. The decrease in the elimination of phenolsulphonephthalein, which occurs in
      uranium, chromate, and cantharidin nephritides, and which, in a general way, is
      proportional to the dose of the poison, bears no constant relation to the changes
      in the nitrogen or chloride elimination. 7. A marked decrease in the elimination
      of the phenolsulphonephthalein occurs synchronously, as a rule, with the onset of
      the symptoms of intoxication (vomiting), and therefore the
      phenolsulphonephthalein test would seem to be a better indicator of the ability
      of the kidney to eliminate the toxic substance responsible for the symptoms of
      renal insufficiency than are either the anatomic changes or the elimination of
      total nitrogen or of chlorides.

PMID- 19867483
TI  - SO-CALLED BIOLOGICAL TESTS FOR ADRENALIN IN BLOOD, WITH SOME OBSERVATIONS ON
      ARTERIAL HYPERTONUS.
AB  - 1. The combination of a biological test object on which adrenalin causes
      contraction of smooth muscle (perfused blood-vessels or the uterus in certain
      conditions) with a biological test object on which it produces inhibition of
      contraction of smooth muscle (intestine) greatly diminishes the chance of error
      in testing blood (or other body liquids) for adrenalin. A control experiment with
      adrenalin solutions should, in general, accompany each observation on the blood.
      2. When properly chosen biological tests are employed, no evidence is obtained of
      the presence of adrenalin in detectable amount in normal blood taken from the
      general circulation. 3. In a case of nephritis with albuminuria and persistently
      high arterial pressure, the pressure was diminished by forced breathing. The
      washing out of carbon dioxide seemed to be a factor in this diminution as well as
      the mechanical interference with the circulation. In this case, the
      administration of large doses of sodium bicarbonate was associated with a marked
      diminution in the blood pressure. 4. In another case with persistently high blood
      pressure, the drawing off of cerebrospinal fluid caused a distinct diminution in
      the arterial pressure, presumably by lowering the intracranial pressure. No
      pressor substance was detected in the cerebrospinal fluid.

PMID- 19867484
TI  - BILIARY CIRRHOSIS IN THE RABBIT.

PMID- 19867485
TI  - ON THE RELATION OF THE OPTIC THALAMUS TO RESPIRATION, CIRCULATION, TEMPERATURE,
      AND THE SPLEEN.
AB  - From what has already been said, it is apparent that changes in respiration and
      blood pressure may be produced by stimulation of a very large portion of the
      optic thalamus; that no one region controls these phenomena; that the spleen
      shows variations in volume only when marked blood pressure changes occur, and
      that such a change has been observed on stimulation of many places in the
      thalamus. Furthermore, the regions in the thalamus from which such effects are
      obtained are those in which the large afferent paths end; namely, the fillet and
      superior cerebellar peduncle, and a region directly connected with the vagus
      nucleus. The portions of the thalamus which proved inert to stimulation were
      those which in our previous investigation also were inactive; namely, the median
      nucleus, and the upper anterior end of the lateral-the region through which the
      fibers of the median nucleus pass. These phenomena are similar in every respect
      to those observed when an afferent nerve is stimulated. In what has gone before,
      it has been shown that the respiratory and circulatory changes occurred when one
      of the sensory paths, or a path running directly to the medullary nuclei
      governing these functions was stimulated. In explaining these phenomena,
      therefore, there is no necessity for invoking the existence of special centers.

PMID- 19867487
TI  - THE PATHOLOGY OF INTRAPERITONEAL BILE INJECTIONS IN THE RABBIT.

PMID- 19867486
TI  - A METHOD FOR THE QUANTITATIVE DETERMINATION OF FECAL BACTERIA.
AB  - From results of which the foregoing data form a part, it appears that the amount
      of bacterial nitrogen in the feces is a valuable index to intestinal conditions,
      and the method herein described is a simple and satisfactory one for making this
      determination. It involves three serial centrifugalizations of a two gram sample
      of the fresh feces brought into suspension in 0.2 per cent. hydrochloric acid.
      The bacterial suspension finally obtained is concentrated and extracted by
      alcohol, and nitrogen is determined in the precipitated material. The complete
      data on a given stool can be obtained in about five days, and one operator can
      take care of three or four stools in duplicate in one day. On an absolutely
      uniform diet of simple and easily digested food during a period of three to four
      weeks, the average amount of bacterial nitrogen in two subjects was found to be
      53.9 per cent. of the total fecal nitrogen, and this percentage, though higher
      than that obtained by workers heretofore, is probably more nearly a true value
      for bacterial nitrogen, because no ether extraction was employed. The average
      daily amount of dry bacteria, calculated on the basis of the nitrogen values, is
      8.27 grams.

PMID- 19867488
TI  - THE CULTIVATION OF TISSUES IN VITRO AS A METHOD FOR THE STUDY OF CYTOTOXINS.
AB  - 1. Theoretically, the method of cultivating tissues outside the body offers an
      ideal technique for the demonstration and study of cytotoxins. 2. Mouse sarcoma,
      which grows vigorously in the plasma of normal rats, shows little or no activity
      in the plasma of rats immunized by mouse sarcoma injections. 3. Rat sarcoma,
      readily cultivated in the plasma of normal guinea pigs, either remains quite
      inactive, or presents a feeble growth in the plasma of guinea pigs previously
      treated with rat tissues. 4. The inhibition of growth in cultures of rat and
      mouse sarcomata in plasma from animals of a foreign species immunized against
      these tissues, is due, in all probability, to the action of cytotoxins.

PMID- 19867489
TI  - A STUDY OF THE ELIMINATION OF PHENOLSULPHONEPHTHALEIN IN VARIOUS EXPERIMENTAL
      LESIONS OF THE KIDNEY.
AB  - The study of a variety of experimental renal lesions in the dog demonstrates that
      the phenolsulphonephthalein test of Rowntree and Geraghty is one of the most
      satisfactory and at the same time most delicate methods of estimating the
      functional activity of the kidney. The elimination of the test dye is decreased
      in so-called spontaneous nephritis and in experimental nephritis due to potassium
      chromate, uranium nitrate, cantharidin, diphtheria toxin, and arsenic, and in
      those lesions caused by snake venom, hemolytic serum, prolonged renal anemia, and
      extensive reduction of the kidney substance. Its elimination is not' diminished,
      but is increased, in the presence of the renal lesion caused by nephrotoxic
      immune serum, and for this discrepancy no explanation is at hand. The test is a
      reliable method of demonstrating improvement in the functional activity of the
      kidney, as is shown in our study of spontaneous nephritis. The increased
      elimination of the dye occurring after small doses of various irritants, which is
      frequently characteristic of the early stages of a severe nephritis, and which is
      seen also several days after unilateral nephrectomy, would appear to have an
      important relation to the problem of kidney function; and although probably not
      of clinical importance, it is worthy of further study as a phase of renal
      activity.

PMID- 19867490
TI  - LETHAL CARDIAC ANAPHYLAXIS IN THE RABBIT : FOURTH COMMUNICATION.
AB  - Acute lethal anaphylaxis in the intact rabbit is caused by a failure of the
      heart. This failure of the heart is due to a change in the heart itself; it is
      peripheral and independent of the central nervous system for its production. This
      change in the heart is shown anatomically and functionally by decreased
      translucency, change in consistency, and by failure to respond to stimuli, and is
      probably to be classed as a chemical rigor. The rigor of the heart is most
      pronounced in the right ventricle, the wall of which may be gray, stiff, very
      tough to the finger nail, and non-irritable. Cardiac stimulants of the digitalis
      group seem to exert a harmful effect when injected in acute anaphylaxis. Blood
      coagulation is delayed; a loose clot forms after one half to two hours. Anti
      anaphylaxis is produced when the animal does not succumb to the injection. When
      anaphylactic death is delayed for about one hour, a well developed rigor of the
      white muscles of the thigh, and of the diaphragm may occur while the animal is
      still alive. Reasons are brought forward to show the necessity of more caution in
      employing the word anaphylaxis. Friedberger's statement, that the lungs of guinea
      pigs dead from acute anaphylaxis are not characteristic of anaphylaxis for this
      animal, is shown to be baseless.

PMID- 19867491
TI  - A NOTE ON SALVARSAN AND ACUTE ANAPHYLAXIS.

PMID- 19867492
TI  - ON HYPERTROPHY AND REGENERATION OF THE ISLANDS OF LANGERHANS.
AB  - 1. Hypertrophy of the islands of Langerhans occurs in two forms: (1) the simple
      type which is nothing more than an increase in size of preexisting islands; and
      (2) the columnar type, in which the islands are composed of anastomosing columns
      of cylindrical cells. 2. Regeneration of the islands of Langerhans takes place by
      means of a budding off of columnar cells from the ducts. The process is analogous
      to the development of the islands in the fetal pancreas. 3. Newly formed islands
      of Langerhans are composed of cylindrical cells similar in all respects to those
      constituting hypertrophied islands of the columnar type. The two structures are
      identical, the latter being a later phase of the former. 4. Newly formed islands
      of Langerhans are capable of a greater hypertrophy than preexisting islands. Both
      types of insular hypertrophy are usually of a compensatory character, the
      columnar, or regenerative type, being the more important. 5. Hypertrophy and
      regeneration of the islands of Langerhans occur most frequently in diabetes
      mellitus (34 per cent. of 100 cases studied). These changes are usually
      associated with sclerosis or hyaline degeneration of other islands. 6.
      Hypertrophy and regeneration of the islands of Langerhans are occasionally
      observed in cirrhosis and carcinoma of the pancreas. In some of the most advanced
      cases, however, the islands have been spared and neither hypertrophy nor
      regeneration are present. 7. Regeneration of the islands of Langerhans has been
      noted in five cases in which there was no evidence of diabetes and where the
      pancreas was for the most part normal. In four of these cases, columnar
      hypertrophy of the islands was also observed. All five cases were associated with
      abnormalities of the larger ducts-obstruction, chronic inflammation, and
      adenomatous proliferation of the lining epithelium. 8. The occurrence of
      hypertrophy and regeneration of the islands of Langerhans affords considerable
      evidence in favor of their anatomic and functional independence.

PMID- 19867493
TI  - A STUDY OF THE PRESPHYGMIC PERIOD WITH THE MICROGRAPH.

PMID- 19867494
TI  - INTRA-STOMACHAL AND INTRA-INTESTINAL INOCULATIONS OF TRYPANOSOME VIRUS WITH TESTS
      FOR IMMUNITY.
AB  - In nearly 50 per cent. of the cases, virulent trypanosome virus inoculated
      directly through the stomach wall of rats failed to infect these animals. The
      percentage of infections after inoculation of this kind seemed to vary with the
      virus. Surra of India proved to be the most virulent, and caderas the least.
      Nagana and dourine occupied intermediate positions. The rats that escaped
      infection showed no trace of immunity when tested with small quantities of the
      same virus between the twelfth and the twenty-eighth days after the intra
      stomachal inoculations. The majority of the rats tested for immunity with surra
      of India and nagana seemed to have acquired, instead of an immunity, a certain
      hypersensitiveness to infection. Five of the seven nagana rats died before their
      controls. The results of testing the vitality of the trypanosomes of caderas,
      dourine, and nagana introduced directly into the stomachs and intestines of
      living rats seem to show that both motility and virulence are usually lost in
      less than two hours. Surra of India proved exceptionally resistant to the harmful
      influences of the stomach, for in one case, surra trypanosomes introduced into
      the intestines were found to be sluggishly motile in the stomach one hour and
      fifty-five minutes later, and in another instance, surra parasites injected into
      the stomach were found, when removed from that organ two hours later, to be
      actively motile and infectious.

PMID- 19867495
TI  - A CHEMO-BIOLOGICAL STUDY OF THE RELATIONS OF PEPSIN TO SO-CALLED ANTI-PEPSIN.
AB  - 1. Fresh and inactivated animal serum under proper conditions will bind pepsin
      quantitatively in weak acid solution and will prevent it from digesting proteid
      even after the addition of free hydrochloric acid in excess. 2. This binding and
      inactivation of pepsin cannot be considered as due to a specific anti-pepsin. 3.
      The phenomenon has been named pepsin deviation in analogy with the deviation
      described for other ferments, notably trypsin. 4. The ability of animal serum to
      deviate pepsin has been responsible for most, if not all, of the published
      accounts of anti-pepsin. 5. By the use of a technique elaborated to control
      pepsin deviation, it has been found impossible to demonstrate normal anti-pepsin
      in the blood serum of the dog, cat, guinea pig, beef, horse, rabbit, and of man.

PMID- 19867496
TI  - A NOTE ON THE ABSENCE OF ADRENALIN IN MALIGNANT RENAL HYPERNEPHROMAS.
AB  - The results of these experiments show, in short, that, by the method employed,
      adrenalin could neither be demonstrated in the specimen of blood, nor in either
      of the two specimens of malignant hypernephroma, nor in the specimen of
      metastatic tissue from the adrenal tumor which closely resembled a malignant
      hypernephroma. The results agree with those of Greer and Wells in showing that no
      adrenalin is found in malignant renal hypernephromas; and the further observation
      is made that no adrenalin content of the blood of a patient with malignant renal
      hypernephroma could be shown by the rabbit uterus strip test. Those rare tumors
      which arise from medullary adrenal tissue might be expected to contain adrenalin;
      but as pointed out by Greer and Wells, since the ordinary malignant renal
      hypernephroma arises from adrenal rests which consist of cortical tissue, and
      since the cortex of adrenal contains no adrenalin, no adrenalin should be
      expected in the tumors arising from such cortical tissue.

PMID- 19867497
TI  - A CUTANEOUS REACTION IN SYPHILIS.
AB  - 1. I have proposed the name luetin for an emulsion or extract of pure cultures of
      Treponema pallidum which is designed to be employed for obtaining, in suitable
      cases, a specific cutaneous reaction that may become a valuable diagnostic sign
      in certain stages or forms of syphilitic infection. 2. The repeated inoculation
      of either living or killed pallida into the testicles of rabbits leads to a
      condition in which an intradermic injection of luetin is followed by a well
      marked inflammatory reaction. A corresponding reaction has been obtained neither
      in rabbits suffering from active syphilitic orchitis, nor in those in which the
      condition had been cured by the administration of salvarsan four months
      previously. Normal rabbits, likewise, do not react to the luetin. 3. The luetin
      produces a similar cutaneous reaction in syphilitic and parasyphilitic patients
      that is most constant and severe in the tertiary and hereditary affections. In my
      series of cases, it was present constantly (100 per cent.) in the manifest
      tertiary affection, in 94 per cent. of latent tertiary affection, and in 96 per
      cent. of the hereditary affection. 4. During the primary and secondary stages,
      the reaction is infrequent, and when present it is of mild degree. An exception
      has been found in cases in which energetic treatment has been or is being carried
      out and in which clinical signs of syphilis are absent. Such cases may show a
      severe reaction. Apparently this is true especially of the cases treated with
      salvarsan. 5. In certain cases of old infection in which no treatment has been
      taken and in which no symptoms have appeared for many years, and in the course of
      which miscarriages have not occurred, the cutaneous reaction has failed to
      appear. But, despite the absence of symptoms, mothers who have young syphilitic
      children have usually given the reaction. 6. It remains to be determined in how
      far the cutaneous reaction with luetin can be used to supplement the Wassermann
      reaction in determining the complete and permanent suppression of a syphilitic
      affection. 7. It appears probable that the Wassermann reaction is more constant
      in the primary and secondary, and the cutaneous reaction in the tertiary and
      latent forms of syphilis. Moreover, it appears that the Wassermann reaction is
      more directly and immediately affected by antisyphilitic treatment than is the
      cutaneous reaction. 8. A more active preparation of luetin can certainly be
      produced by improved methods. This phase of the subject is being considered at
      the present time and will be reported upon in a later paper.

PMID- 19867498
TI  - THE STATUS OF RESPIRATION IN THE METHODS OF DIFFERENTIAL PRESSURE COMPARED WITH
      THAT UNDER THE METHOD OF INTRATRACHEAL INSUFFLATION.
AB  - The maintenance of life of an individual with an open double pneumothorax under
      differential pressure depends essentially upon the normal position of the lower
      lobes of the lungs and their close approximation to the diaphragm, especially of
      the posterior parts of the lobes. A complete dislodgment of both lower lobes
      leads invariably to the death of the individual, which may occur in a very short
      time, or after fifteen to twenty-five minutes. In all cases the respiration is
      affected first; it slows almost at once and stops invariably before the heart.
      The result is the same whether the vagi are intact or both nerves are cut.
      Exceptionally, respiration may continue even after the separation of the lungs
      from the diaphragm, but only by having all the lobes well approximated to the
      thoracic walls. When by dislodgment of the lower lobes the respiration is stopped
      and the heart is feeble and slow, or stopped completely, it is rarely possible to
      restore life by artificial respiration or by other appropriate means. The extent
      of the exchange of gases occurring in normal respiration, with closed thoracic
      cavity, exceeds greatly the need for the maintenance of life, since normal
      respiration is provided with an abundance of factors of safety. Under
      differential pressure, however, life is carried on with an exchange of gases
      which amounts to a small fraction only of the extent of the exchange that takes
      place in normal respiration; respiration under differential pressure is,
      therefore, deprived of all factors of safety and is incapable of resisting the
      dangers of exceptional incidents. Deaths occurring in connection with the
      differential pressure have their cause essentially in this unguarded state of the
      function of respiration. Under tracheal insufflation, the function of respiration
      is surrounded with effective safeguards, at least as much as is normal
      respiration. Dislodgment of the lungs has no detrimental effect. After complete
      collapse of the lungs, capillary adhesions within the alveoli and the small
      bronchi become an additional obstacle to the redistension and respiration.
      Differential pressure holds this obstacle in abeyance. When the lungs become
      collapsed during an open pneumothorax, it should be kept in mind that the force
      which is required for redistension is greater than that which is sufficient to
      keep the lungs continually distended. At the beginning of a redistension,
      therefore, a higher pressure should be employed for a short time.

PMID- 19867499
TI  - STUDIES ON THE VENOUS PULSE : II. THE TIME RELATIONS OF THEVENOUS PULSE AND THE
      HEART SOUNDS.
AB  - This investigation comprises a study of venous pulse, carotid, cardiographic, and
      heart sound records from twenty-one men with normal hearts. The heart sounds were
      recorded by the method of Einthoven. When correction is made for transmission,
      the first heart sound begins, on an average, 0.131 of a second before the c-wave
      of the venous pulse, and has an average duration of 0.128 of a second. The second
      heart sound begins a few hundredths of a second before the v-wave and has a
      duration of 0.091 of a second. The third heart sound occurs shortly before or is
      coincident with the beginning of the h-wave. It has an average duration of about
      0.03 of a second. Considerable variation from the average positions are noted in
      individual cases. This is especially true in the relation between the second
      heart sound and the v-wave. Measurements of the venous pulse and heart sound
      intervals show that the a-c, c-v, and v-h venous pulse intervals, the first to
      second and the second to third heart sound intervals, and systole tend to remain
      fairly constant in length when cardiac cycles of different length are considered.
      The v-a, h-a, and x-a venous pulse intervals, the third to first heart sound
      interval, and diastole tend to vary in length with variations in total length of
      the cycle. Records of the venous pulse and heart sound obtained from dogs show a
      similar relation to that found in man. The main difference observed was an
      earlier occurrence of the first heart sound before the c-wave of the venous
      pulse.

PMID- 19867500
TI  - THE BIOCHEMISTRY OF BACILLUS LEPRAE.

PMID- 19867501
TI  - THE RELATION OF HEMATIN TO PATHOLOGICAL PIGMENT FORMATION.
AB  - 1. It has been shown that powdered hematin is exceedingly resistant to the
      metabolic action of tissue cells, and wherever injected it will remain for weeks
      with but slight and slowly progressing alteration. 2. The changes produced in
      hematin by tissue cells are identical with those changes resulting from the
      oxidation of hematin by hydrogen peroxid, forming a series of bodies of
      decreasing color intensity, which manifest an iron reaction in inverse proportion
      to their color. 3. These hemosideroid pigments are distinguished from true
      hemosiderin by the type of their iron reaction, by their solubility in dilute
      alkalies, and by their destructive oxidation by hydrogen peroxid. 4. Crystalline
      hematin injected into the tissues is subject to the same changes as powdered
      hematin. 3. Whereas powdered parahemosiderin is converted into hemosiderin by the
      tissue cells with comparative ease, powdered hematin shows no such conversion
      within forty-seven days, and as the only demonstrable change produced in hematin
      by the tissue cells does not result in the formation of either hemosiderin or
      hematoidin, the assumption that hematin is the progenitor of these pigments seems
      unwarranted.

PMID- 19867502
TI  - THE EFFECTS OF SUBDURAL INJECTIONS OF LEUCOCYTES ON THE DEVELOPMENT AND COURSE OF
      EXPERIMENTAL TUBERCULOUS MENINGITIS.
AB  - Subdural inoculation of tubercle bacilli of established virulence for guinea pigs
      and rabbits, produces in the dog a tuberculous meningitis, followed by paralysis
      and death. When suspensions of canine leucocytes are injected subdurally,
      following such inoculations there occurs uniformly a delay in the development of
      the paralysis and a prolongation of the life of the treated animal. In dogs
      inoculated with small doses of tubercle bacilli of low virulence, the development
      of paralysis has been prevented by this means for periods of seven months (up to
      the present date), while the untreated animals injected with the same cultures
      have all developed paralytic symptoms within a period of about four weeks.

PMID- 19867503
TI  - THE ISLANDS OF LANGERHANS AFTER LIGATION OF THE PANCREATIC DUCTS.

PMID- 19867504
TI  - STUDIES WITH THE ELECTROCARDIOGRAPH ON THE ACTION OF THE VAGUS NERVE ON THE HUMAN
      HEART : II. THE EFFECTS OF VAGUS STIMULATION ON THE HEARTS OF CHILDREN WITH
      CHRONIC VALVULAR DISEASE.
AB  - The electrocardiographic records taken during vagus stimulation by pressure from
      children suffering with chronic heart disease have shown that the stimulation of
      the vagi in these cases is strikingly effectual. In some of the cases, a definite
      difference was demonstrated between the action of the right and left vagi. The
      control of the rate of the heart-beat seemed to predominate usually in the right
      vagus nerve, while the control of stimulus conduction from auricles to ventricles
      apparently predominated usually in the left vagus. This difference in the two
      nerves probably exists on account of the difference in their anatomical
      distribution, the right vagus going especially to that part of the heart which
      controls the rate of contraction, the sinus node above the right auricle, and the
      left vagus going especially to that part in which the conducting mechanism is
      found. Each nerve, however, has to a lesser degree the function which
      predominates in the other. The whole heart seems to respond, as a rule, more
      promptly to right than to left vagus pressure, and fairly constant differences
      have been seen in the effects which stimulation of each nerve has on the various
      waves of the electrocardiograms. The stimulation of each vagus may influence
      directly the contractions of the ventricles, causing great diminution in their
      force. Right vagus stimulation was followed at times by a complete dissociation
      of auricles and ventricles. The auricular rhythm was slowed sufficiently at this
      time to allow the ventricles, whose inherent rhythmicity is apparently unaffected
      by right vagus stimulation, to take up their own independent rhythm. The
      heightened ventricular rhythmicity in these cases allowed this to take place
      after only moderate slowing of the auricles. The independent ventricular rhythm
      was sometimes established in the region of the node of Tawara, for no disturbance
      of the ventricular portion of the electrocardiogram occurred. At another time,
      some other point in the ventricles inaugurated the stimuli of the independent
      ventricular contractions and an abnormal electrocardiogram resulted. The
      resemblance of our curves, showing dissociation, to those obtained during right
      vagus and left accelerator stimulation in dogs is definite. That analogy, the
      clinical picture, and the form of the electrocardiograms of these cases have led
      us to the belief that an important feature in the pathological physiology of
      these cases is hypertonus of the cardiac accelerator nerves. This factor, as a
      cause of symptoms and as a hindrance to the establishment of cardiac rest, may
      prove of great importance, against which a new form of cardiac therapeutics must
      be directed.

PMID- 19867505
TI  - AURICULAR TACHYCARDIA WITH A CONSIDERATION OF CERTAIN DIFFERENCES BETWEEN THE TWO
      VAGI.

PMID- 19867506
TI  - THE EFFECTS OF SPLENECTOMY UPON THE CELL CONTENT OF THE THORACIC DUCT LYMPH IN
      THE DOG, AND ITS RELATION TO THE ACTION OF PILOCARPIN.
AB  - 1. Splenectomy in dogs results in an immediate increase of cells in the thoracic
      duct lymph, due to the manipulation involved in the operation. This increase is
      soon followed by a low cell count, attributable to the removal of an important
      source of the cells under consideration. Several months after the operation, a
      normal cell count is reestablished, due probably to a readjustment of activity on
      the part of other cell-forming tissues. 2. Pilocarpin injections after
      splenectomy result in an increase of cells, attributable to an increased activity
      of the respiratory organs and of the intestine. 3. After the injection of
      pilocarpin, splenectomy may increase the cell count, but it causes a decrease
      sooner than in cases of pilocarpin injection not followed by splenectomy.

PMID- 19867507
TI  - CULTURAL STUDIES ON MOUTH SPIROCHAETAE (TREPONEMA MICRODENTIUM AND MACRODENTIUM).
AB  - I have described the successful cultivation of two distinct species of Treponema
      from the oral cavity of man. The species differ from one another morphologically
      and in respect to their cultural properties. As the two species have now been
      clearly separated and cultivated for the first time, I propose for them the names
      Treponema microdentium and macrodentium, respectively. Division along the
      longitudinal axis has been demonstrated for both Treponema macrodentium and
      microdentium. When the micro- and macrodentium are cultivated under imperfect
      anaerobic conditions, they undergo involution, but still continue to vegetate to
      some extent. Finally, a spiral organism has been cultivated and described that
      may be merely an involuted form of the macrodentium, or it may be a new species
      altogether.

PMID- 19867508
TI  - THE DIRECT CULTIVATION OF TREPONEMA PALLIDUM PATHOGENIC FOR THE MONKEY.
AB  - A method for the direct cultivation of Treponema pallidum from human syphilitic
      lesions, by the employment of a solid medium, has been described. By means of it,
      three of the four strains worked with were successfully cultivated. The several
      pure cultures agree in morphological and cultural characters, grow only in the
      presence of sterile tissue under anaerobic conditions, and do not produce
      putrefactive odors. The morphology is typical under optimum cultural conditions;
      it becomes atypical when the conditions are unfavorable. In cultures, Treponema
      pallidum multiplies by longitudinal division. The process is usually symmetrical
      but occasionally appears to be asymmetrical. Inoculation of the pure cultures
      into the skin of two species of lower monkeys was followed by the production of
      lesions resembling the primary syphilitic lesion occurring in man and those
      caused in the monkey by inoculation of spirochaetae-containing serum from human
      sources. During the course of the positive inoculation in the monkey, the blood
      develops the property of giving a positive Wassermann reaction. Thus the relation
      of Treponema pallidum to this reaction is supported, and the identity of the
      cultivated strains with the species found in human syphilitic lesions
      established.

PMID- 19867509
TI  - CHEMICAL STUDIES ON INTESTINAL INFANTILISM : I. ENDOGENOUS METABOLISM: KREATININ,
      KREATIN, URIC ACID.
AB  - In my three cases of intestinal infantilism, the kreatinin excretion was more
      irregular than normally, and the kreatinin coefficient was low. Kreatin was found
      in the urine on a kreatin-free diet. The sum of kreatinin and kreatin was also
      irregular. The endogenous uric acid was irregular from day to day. The kreatin
      excretion is apparently lower on a high fat diet than on a high carbohydrate
      diet.

PMID- 19867510
TI  - CHEMICAL STUDIES ON INTESTINAL INFANTILISM : II. THE RELATION OF ENDOGENOUS TO
      EXOGENOUS METABOLISM: NITROGEN AND SULPHUR DISTRIBUTION, AND CALORIMETER
      EXPERIMENTS.
AB  - In three cases of intestinal infantilism, the excretion of nitrogen in the urine
      per square meter of body surface was low. The heat radiation was normal. In spite
      of the fact that the absolute quantity of nitrogen was low, the distribution of
      nitrogen and sulphur among the various nitrogen and sulphur constituents of the
      urine was in the normal ratio. The ammonia excretion was normal. The ethereal
      sulphates were slightly increased. The respiratory coefficient showed that the
      supply of glycogen had not been used up after eighteen hours' starvation.

PMID- 19867511
TI  - THE BEHAVIOR OF CHICKEN SARCOMA IMPLANTED IN THE DEVELOPING EMBRYO.
AB  - The direct inoculation of a sarcoma of the fowl into the developing chick embryo
      or its membranes has yielded growths in many cases. The best results have been
      obtained with grafts of the living tumor tissue, but, as in the adult, growths
      can be engendered with dried tissue or with the Berkefeld filtrate of a tumor
      extract. When living tumor tissue is used, an actual transplantation occurs. The
      neoplasms developing are spindle-celled sarcomata, remarkably uniform in
      structure, and similar to those in the adult fowl, except that in the embryo the
      neoplastic cells are often extremely long and slender, and the structure of the
      growth is very loose. The membranes adapt themselves in a remarkable way to the
      support of the tumors. In them, the growth is seldom invasive; and while regional
      metastases are occasionally seen, none occur by the bloodstream, despite the
      predilection of the growth for this path of distribution in adult hosts. In the
      more resistant structures of the embryo itself, an invasive extension of the
      sarcoma occurs. Growths originally in the yolk-sac outside the chick may be
      carried into the latter during the course of development. Secondary growths in
      the viscera may cause the death of the host some weeks after hatching. In order
      to produce tumors in the embryo, the sarcoma cells or the agent engendering the
      growth must be brought into a direct association with the mesodermal tissues.
      This necessity is responsible for interesting differences in the location of the
      growths in the various membranes. The sarcoma will grow in the membranes of
      pigeon or duck embryos, whereas in adults of these species it will not do so; and
      in chicken embryos of different varieties, it grows uniformly well, a finding not
      obtained in adults. In embryo hosts of all the sorts mentioned, there is a total
      absence of the cellular reaction which in adults indicates resistance to the
      tumor's development. Relatively speaking, the embryo seems much more favorable
      than the adult as a host for the sarcoma.

PMID- 19867512
TI  - EXPERIMENTAL PNEUMONIA BY INTRABRONCHIAL INSUFFLATION.
AB  - The numerous attempts made in the last twenty-five years to reproduce lobar
      pneumonia in animals practically failed in all instances. By intrabronchial
      insufflation of pure cultures of pneumococcus in dogs, we produced experimental
      pneumonia successively in forty-two cases, with a mortality of at least 16 per
      cent. The fatal cases resembled closely lobar pneumonia in man. In the non-fatal
      cases, the pathological and bacteriological findings were again in accord with
      the findings in man. Clinically, however, the cases of nonfatal experimental
      pneumonia run a milder and shorter course than in man. In a few instances, lobar
      pneumonia has been produced experimentally also with the Pneumococcus mucosus and
      with Friedlander's pneumobacillus. The anatomical findings in these experiments
      have shown some characteristics agreeing with the findings in the pneumonias of
      man produced by these organisms. The quantity of the injected culture seemed to
      have a definite influence upon the outcome of the disease; in the fatal cases
      larger quantities of the culture had been injected. The animals were neither
      selected nor prepared in any manner. The experimental success did not, therefore,
      appear to depend upon the degree of resistance of the individual hosts. It is
      suggested that the uniformly successful results of the experiments were due to
      the obliteration of a large number of bronchi by the injected culture, through
      which mechanical effect a favorable opportunity was provided the pneumococci to
      develop and display their pathogenic activities consisting in the calling forth
      of a characteristic local, more or less effective, widespread, inflammatory
      reaction of the lung tissue.

PMID- 19867513
TI  - THE PRODUCTION OF PASSIVE HYPERSENSITIVENESS TO TUBERCULIN : A PRELIMINARY
      REPORT.

PMID- 19867514
TI  - STUDIES ON IMMUNITY IN CANCERS OF THE WHITE RAT : THE "PRECANCEROUS STATE" AND
      THE MECHANISM OF THE ORGAN RESISTANCE TO TUMOR GROWTH.

PMID- 19867515
TI  - THE PRESSOR INFLUENCE OF AUGMENTED BREATHING.

PMID- 19867516
TI  - MORPHOLOGICAL AND PATHOGENIC VARIATIONS IN TREPONEMA PALLIDUM.
AB  - When many cultures of Treponema pallidum, whether obtained from the testicular
      lesions produced in rabbits or directly from human cases of syphilis, are
      compared, certain definite differences in morphological character become
      apparent. The different specimens can be divided into thicker and thinner forms
      or types, and an average or normal form or type. The last is the common or most
      frequent variety, but the other two occur with sufficient frequency and retain
      their characters with such constancy as to constitute distinct varieties. Indeed,
      two of the varieties-the average and the thinner-occurred in association in a
      chancre and were separated afterwards in cultures. The gross cultural properties
      of the three varieties present no points of distinction. The lesions caused in
      the testicle of the rabbit differ according to the variety inoculated, and
      consist either of a diffuse or of a nodular orchitis. This is a highly important
      distinction, and if, in the study of a still larger number of specimens of
      pallida, it is maintained, it is capable of throwing light on certain important
      clinical features of the human syphilitic disease. The thinner variety of
      Treponema pallidum resembles in morphology Treponema microdentium, from which it
      is unmistakably distinguished by cultural characters. The morphological and
      pathogenic variations in cultures of the pallidum may constitute racial
      differences within the species.

PMID- 19867517
TI  - REPORT OF A DOG MAINTAINED IN GOOD HEALTH BY A PARATHYROID AUTOGRAFT
      APPROXIMATELY ONE FOURTH OF A MILLIMETER IN DIAMETER AND COMMENTS ON THE
      DEVELOPMENT OF THE OPERATION FOR GRAVES' DISEASE AS INFLUENCED BY THE RESULTS OF
      EXPERIMENTS ON ANIMALS.

PMID- 19867518
TI  - A BULKHEAD SUTURE OF THE INTESTINE.

PMID- 19867519
TI  - ON THE LESIONS PRODUCED IN THE APPENDIX BY OXYURIS VERMICULARIS AND
      TRICHOCEPHALUS TRICHIURA.
AB  - 1. In a study of 129 cases of appendicitis in children, we have found that in
      nineteen of them (15 per cent.) the appendix contained Oxyuris vermicularis or
      Trichocephalus trichiura. 2. The oxyuris is much the commoner of the two
      parasites, occurring seventeen times, while the trichocephalus was found only
      twice. 3. In fifteen out of the nineteen cases, the parasites were associated
      with a non-suppurative catarrhal type of appendicitis. If the four cases of
      catarrhal oxyuris appendicitis of adults be also included, it may be said that 83
      per cent. of the cases of appendicitis associated with parasites have been of the
      catarrhal type. In the four remaining cases, the appendix was gangrenous. The
      cellular changes noted in the catarrhal cases have been distension of the crypts
      with mucus, hyperplasia of the lymph follicles, and in some cases, the presence
      of a few leukocytes in the muscularis and serosa. 4. In thirteen of the nineteen
      cases (70 per cent.), there have been noted, in addition to the cellular changes,
      certain lesions in the mucosa, unquestionably produced by the parasite. Of the
      six cases in which no specific lesions were demonstrated, the extensive gangrene
      in three of them might have obliterated specific lesions had they been present.
      Specific lesions were not demonstrated in any one of the four adult cases. 5. The
      oxyuris injures the mucosa by breaking through the lining epithelium and
      burrowing into the lymph follicles for a greater or less distance. Its invasion
      is usually accompanied by extravasation of blood into the surrounding lymphoid
      tissue, and its escape through the ruptured mucosa. In some cases, the oxyuris
      produces hemorrhagic ulcers in the mucous membrane, the edges of which are
      undermined and the bases formed by the submucosa. A characteristic feature of the
      oxyuris lesions is the absence of inflammatory reaction about them, except in
      those cases where there is secondary bacterial infection. 6. In some instances,
      the oxyuris may become encapsulated in the mucosa with fibrous tissue, and itself
      undergo hyaline degeneration. Such a process constitutes a healed oxyuris lesion.
      7. The trichocephalus attacks the mucous membrane of the appendix in a manner
      similar to that described for the oxyuris, and there is the same absence of
      inflammation about the invading parasite. The trichocephalus, however, instead of
      invading a lymph follicle, shows a tendency to burrow along just beneath the
      columnar epithelium. 8. The conclusion to be drawn from these facts is that
      oxyuris and trichocephalus, when they occur in a diseased appendix, are, in most
      cases, the existing cause of the pathological changes found.

PMID- 19867520
TI  - PREGNANCY AND CHLOROFORM ANESTHESIA : A STUDY OF THE MATERNAL, PLACENTAL, AND
      FETAL TISSUES.
AB  - Pregnant dogs are susceptible to chloroform administered shortly before delivery
      or during labor, and show the same degree of liver injury as normal dogs, or even
      a somewhat greater one. Chloroform anesthesia may cause more or less hyaline
      necrosis in the border zone between the maternal and fetal parts of the placenta
      that may lead to hemorrhage, placental separation, and premature delivery.
      Chloroform anesthesia causes no injury to the liver of the fetus nor to any other
      fetal organ, in spite of the fact that it can be demonstrated to be present in
      these tissues. These experiments raise objections to the use of chloroform in
      pregnant women where an anesthetic must be continued for half an hour or longer.
      Chloroform anesthesia may be admissible for the few minutes at the end of the
      delivery, but when operative measures are necessary, before or after delivery, it
      is a dangerous anesthetic and surely capable of producing injury to the liver in
      the manner recognized in the case of normal persons. Objections may be raised to
      the application of conclusions derived from experiments on dogs to human cases;
      but the similarity of the effects of chloroform in man and dog surely affords a
      sound basis of comparison. Two fundamental facts would seem to be now
      established: (1) Normal human adults may be fatally poisoned (late chloroform
      poisoning) by chloroform anesthesia of one half to one hour's duration. (2)
      Normal and pregnant dogs are equally susceptible to late chloroform poisoning,
      and may be fatally poisoned by an anesthesia of two hours' duration. Hence one
      may conclude that probably normal and pregnant human beings are equally
      susceptible to chloroform poisoning, that chloroform anesthesia during any part
      of the pregnant period is capable of causing liver necrosis, and, consequently,
      that chloroform is a dangerous anesthetic.

PMID- 19867521
TI  - INSUSCEPTIBILITY OF PUPS TO CHLOROFORM POISONING DURING THE FIRST THREE WEEKS OF
      LIFE.
AB  - Employing the liver necrosis as an index, we find that pups are immune to the
      poisonous action of chloroform anesthesia. This immunity or resistance to late
      chloroform poisoning is complete in the first week, very striking during the
      second and third weeks, and usually disappears during the fourth week of life.
      Nests of blood-forming cells (blood islands) are numerous in the sinuses of the
      liver during the first week and normally become progressively less numerous each
      week until the liver is almost free from these cells at the end of the fourth
      week of life. It is considered possible that these leucocytes in the blood
      islands protect the liver against the specific action of a known poison
      (chloroform). The mechanism of this hypothetical protective action is not
      understood, but it may consist of a process of neutralization. Perhaps this
      protective action against poisons is an important part of the functions of white
      blood cells and may bear an important relationship to the process of
      inflammation.

PMID- 19867522
TI  - THE HISTOLOGICAL SIGNS OF RESISTANCE TO A TRANSMISSIBLE SARCOMA OF THE FOWL.
AB  - 1. The living tissue of the chicken sarcoma, when implanted in susceptible hosts,
      survives, proliferates, and thus gives rise apparently to the whole of the new
      tumor. The histological findings about the graft do not suggest any other origin
      for the growth. 2. In fowls with a natural or acquired resistance, a very
      striking series of phenomena takes place about the graft or the established
      growth. They are referable to the presence of the living neoplastic cells and are
      essentially similar to those already described in mammals. 3. The lymphocyte has
      an association with the processes of resistance in the fowl, similar to, but more
      marked than that observed in mammals. 4. Resistance of the host does not
      constitute for the chicken tumor a differential means whereby the extrinsic agent
      present in the growth can be observed to engender it. In general, it may be
      stated that, when the new host is so unfavorable to the transplanted sarcoma
      cells as to cause their death, no tumor develops. 5. The activity of the
      extrinsic agent is negligible as affecting the interpretation of the phenomena
      about grafts of the avian sarcoma in resistant and susceptible hosts. They are
      referable to the presence of the transplanted cells. 6. The appearance or non
      appearance of a specific, supporting, and vascularizing reaction in the host
      tissues cannot be looked upon as determining the fate of grafts of the chicken
      sarcoma. The same seems to be true of mammalian neoplasms.

PMID- 19867523
TI  - THE PRODUCTION OF ANTIBODIES BY TISSUES LIVING OUTSIDE OF THE ORGANISM.
AB  - Since guinea pig bone marrow and lymph gland cultivated for five days with goat
      blood generate substances that are hemolytic for goat red blood corpuscles, it
      can be concluded that tissues living outside of the organism react against an
      antigen by the production of an antibody.

PMID- 19867524
TI  - A FURTHER NOTE UPON THE EXPERIMENTAL PRODUCTION OF LEPROSY IN THE MONKEY (MACACUS
      RHESUS), WITH A CRITICAL STUDY OF THE CULTURE EMPLOYED.
AB  - Fatal leprosy, with all its clinical and pathological manifestations in man, may
      be experimentally induced in the monkey (Macacus rhesus) with a pure culture of
      the acid-fast bacillus cultivated by one of us (Duval) from a leprous lesion in
      man. To produce the disease experimentally, it seems necessary to give the animal
      repeated injections of large numbers of leprosy bacilli at given intervals for a
      period of months. That the infection is more likely to follow where sensitization
      is first established is definitely proven by the specific experiments that we
      have carried out upon a variety of laboratory animals. The first injection, we
      assume, sensitizes the animal and may consist of either killed or viable lepra
      bacilli. The necessity of first sensitizing the monkey and then giving repeated
      doses of viable organisms over a long period might explain the relative
      infrequency of the disease in man; at least, it offers an explanation of the fact
      that man rarely, if ever, contracts leprosy, although intimately associated for
      an indefinite period with those afflicted with the disease. The leprous lesions
      in the monkey are histologically indistinguishable from those in man and do not
      essentially resemble the specific lesion of tuberculosis, blastomycosis, or the
      lesions experimentally produced with saprophytic acid-fast species, since the
      appearance of large lepra cells and the arrangement of the bacilli in dense
      packets within these cells to form the so-called globi is a constant and
      characteristic feature for the experimental as well as the human lesion (figures
      17, 18, and 19). The production of leprosy in the monkey proves conclusively that
      the acid-fast bacillus cultivated by one of us (Duval) from the human lesion is
      the Hansen bacillus and not some extraneous saprophyte, and that it is the
      etiological factor in human leprosy. In our experience, it has been extremely
      difficult to produce, in the lower animals, more than a transient localized
      lesion with human leprous material rich in the specific bacilli, unless the
      animal is first sensitized, when lesions histologically identical with those
      produced by pure cultures are easily induced. Therefore, it is natural to expect
      that cultures of Bacillus leproe which are many generations removed from the
      parent stem are less likely to infect, unless given in larger doses on the ground
      of loss in virulence. When experimental leprous lesions occur in the internal
      organs, they are more often found in the liver and spleen, while the experimental
      lesions occasionally produced in the lower animals with some of the saprophyte
      species, such as the bacillus of timothy hay, Moeller's grass bacilli, etc.,
      rarely, if ever, occur in these organs (Abbott and Gildersleeve). These authors
      did not find lesions in the liver and spleen in a single instance after
      inoculating forty-five rabbits intravenously with large doses of the "confusing
      group." Furthermore, the cell picture and the appearance and arrangement of these
      bacilli in the lesions in no way resemble experimental leprosy (Holscher). It is
      no indication that a given culture is not the Hansen bacillus because the
      individual organisms differ in size and shape from those in the tissues, since it
      is a well known fact that marked variations in morphology are common for many
      bacterial species under natural and artificial conditions. One of us (Couret) has
      already pointed out that there is a wide variation in morphology for Bacillus
      leproe under different environments. The experimental work serves not only to
      emphasize this fact, but is proof that a transformation from the slender beaded
      rods of the tissues to solidly staining diplococcoid forms of culture does occur
      for Bacillus leproe; and, conversely, that the coccoid forms of culture may again
      assume the slender beaded appearance by passage through warm-blooded animals.

PMID- 19867525
TI  - THE PATHOGENESIS OF THE HEMORRHAGIC DISEASES OF THE NEW-BORN.
AB  - Those conditions of the new-born characterized by a hemorrhagic tendency,
      icterus, and fatty changes, are probably all syndromes which may occur as the
      result of a number of toxic agents. All of them, however, have been produced, in
      these experiments, by the action of a single experimental agent. Thus, a picture
      indistinguishable from that called Buhl's disease has been obtained by the use of
      chloroform, as have also the pictures known as Winckel's disease, melaena
      neonatorum, etc. Chloroform is not held to be the only substance that has this
      power. It stands rather as one member of a group of agents, the effects of which
      in general and in individual organs are similar to those caused by lack of
      oxygen. The essential features of these conditions have also been produced by
      direct asphyxiation of the fetus. The suggestion is therefore made that
      underlying all these symptoms and pathological complexes, there is a deficiency
      of oxidation, general, local, or selective, thus bringing this group of diseases
      into the general category of acute yellow atrophy of the liver, eclampsia,
      pernicious vomiting, cyclic vomiting, phosphorus poisoning, etc. In human beings,
      chloroform and asphyxia must, in many instances, be the determining causes. There
      remain, however, other cases in which different factors are to be sought.

PMID- 19867526
TI  - GLOMERULAR LESIONS OF SUBACUTE BACTERIAL ENDOCARDITIS.
AB  - 1. In most cases of chronic or subacute bacterial endocarditis due to the
      endocarditis coccus (Streptococcus viridans), there exists a distinctive
      pathological lesion in some of the glomeruli due to bacterial emboli. 2. The
      salient features of the pathological picture are first, the involvement of one or
      more loops of a variable number of glomeruli; secondly, the absence of any
      visible disease in the uninvolved glomeruli and in the uninvolved portions of
      affected glomeruli; and thirdly, the association in most of the bacterial cases
      of all the various stages of the glomerular process often seen in a single
      microscopical section. 3. The lesion does not occur in cases of acute
      endocarditis, and up to the present time it has been absent in cases of subacute
      bacterial endocarditis due to organisms other than the endocarditis coccus. 4. In
      a group of cases having vegetations that are typical of those in the active stage
      of subacute endocarditis (except that they are free from bacteria and healing or
      healed), the healed stage of this distinctive glomerular lesion is present,
      although it is less extensive than in the active bacterial cases. 5. These cases,
      therefore, are most probably examples of subacute bacterial endocarditis due
      originally to the endocarditis coccus, but in which the endocardial vegetations
      have become free from bacteria rather early in their course and are now healing
      or healed, as claimed by Harbitz and Libman. 6. During the active bacterial stage
      of the disease, if the glomerular lesions are not too numerous, the only symptoms
      produced will be an almost constant hematuria, usually demonstrable only
      microscopically. If the glomerular lesions are very numerous, symptoms resembling
      those of subacute hemorrhagic nephritis may occur and may even cause a fatal
      issue. If the glomerular lesions are very numerous but not sufficient to cause
      death, and the cardiac lesion should go on to healing, a contracted kidney,
      secondary to the glomerular lesion, may subsequently ensue and produce the
      typical symptoms and death. In such a case, the finding of the healed or healing
      lesion of subacute bacterial endocarditis will be accidental.

PMID- 19867528
TI  - EXPERIMENTAL INFECTION OF THE MULE WITE TRYPANOSOMA HIPPICUM BY MEANS OF MUSCA
      DOMESTICA.

PMID- 19867527
TI  - ON THE FUNCTION OF THE CIRCLE OF WILLIS.

PMID- 19867529
TI  - THE INFECTION OF MULES BY TRYPANOSOMA HIPPICUM THROUGH MUCOUS MEMBRANES.

PMID- 19867530
TI  - RESPIRATORY WAVES OF BLOOD PRESSURE, WITH AN INVESTIGATION OF A METHOD FOR MAKING
      CONTINUOUS BLOOD PRESSURE RECORDS IN MAN.

PMID- 19867531
TI  - ULTIMATE RESULTS OF AORTIC TRANSPLANTATIONS.
AB  - In the first experiment, a segment of popliteal artery, extirpated from the leg
      of a young man and preserved for twenty-four days in cold storage, was
      transplanted upon the abdominal aorta of a small bitch. The animal lived in
      excellent health for four years and two months, became pregnant several times,
      and finally died during labor. The abdominal aorta was normal, but the human
      arterial segment was slightly dilated, and its wall was composed of connective
      tissue only. In the second experiment, a segment of dog's jugular vein, preserved
      for twenty-four hours in cold storage, was transplanted upon the thoracic aorta
      of a fox terrier. In spite of slight lesions of the cord due to interruption of
      the aortic circulation during the operation, the animal remained in excellent
      health. After two years and two months, the dog died of an epidemic disease. The
      descending aorta was normal. The transplanted segment had about the same caliber
      as that of the aorta, but its wall was composed of connective tissue, with no
      evidence of muscular or elastic tissues. In these two experiments, the walls of
      the transplanted segments contained neither muscle nor elastic tissue fibers and
      were not thicker than those of the artery. Nevertheless, they were able to
      withstand the pressure of the blood without undergoing any marked dilatation. If
      death due to accident had not brought these two experiments to an end, it is
      probable that the transplanted segment would have successfully resisted the
      pressure of the blood for a much longer time. As it is, the result shows that, in
      one experiment after four years and in the other after two years, the segments
      transplanted upon the abdominal and thoracic aortas were still efficient.

PMID- 19867532
TI  - TECHNIQUE FOR CULTIVATING A LARGE QUANTITY OF TISSUE.

PMID- 19867533
TI  - THE INFLUENCE OF HEAT ON DIFFERENT SERA AS CULTURE MEDIA FOR GROWING TISSUES.
AB  - 1. Bone marrow of guinea pigs grows better in autogenic than in homogenic serum.
      2. Bone marrow of guinea pigs grows more extensively and rapidly in unheated than
      in heated autogenic and homogenic serum (56 degrees C. for half an hour). 3. In
      different heterogenic sera, there are differences in the growth of the tissue. In
      none of the sera examined, was the growth so extensive as in homogenic and
      autogenic serum. 4. Heated heterogenic serum is a better culture medium and shows
      more extensive tissue growth than normal unheated heterogenic serum.

PMID- 19867534
TI  - THE CONSTRICTING INFLUENCE OF ADRENALIN UPON THE HUMAN CORONARY ARTERIES.
AB  - 1. Adrenalin causes a marked constriction of the human coronary artery, although
      it undoubtedly produces a relaxation in some mammals; e. g., calf, sheep, pig,
      etc. 2. The human coronary artery is probably provided with sympathetic
      vasoconstrictors. 3. If human blood-vessels are obtained in a warm condition
      within a few hours after death, they are often suitable for biological and
      pharmacological study.

PMID- 19867535
TI  - AN EXPERIMENTAL STUDY OF THE ARTERIES IN SHOCK.
AB  - As a result of the experimental work here recorded, there can be no doubt of the
      fact that the rate of inflow in shock was faster than normally, and in my
      experiments the average increase was 36 per cent. It is concluded, therefore,
      that decreased vasomotor tone is an accompaniment of shock.

PMID- 19867536
TI  - CORRELATION OF THE HISTOLOGICAL AND CHEMICAL CHANGES IN THE SPLEEN DURING
      NECROSIS AND AUTOLYSIS.
AB  - The most marked chemical changes in a disintegrating spleen are noticed during
      the period when karyorrhexis and karyolysis are the characteristic features. When
      pyknosis alone is prominent almost all of the several constituents are in the
      coagulable or precipitable fraction, just as they are in the original normal
      tissue. After karyolysis is practically complete the coagulable and precipitable
      elements of the tissue still gradually decrease in amount, but the rate is far
      below that occurring during karyorrhexis and karyolysis. Moreover, even when
      microscopical nuclear disintegration is practically at an end, the chemical
      process of disintegration is still going on, but very slowly. Finally, when
      nuclear structures can no longer be seen in the spleen, about 72 per cent. of the
      nuclein nitrogen, about 50 per cent. of the original insoluble phosphorus, and 70
      per cent. of the original insoluble nitrogen, are still in the insoluble form
      (precipitable and coagulable by alcohol), while about two thirds of the
      phosphatid phosphorus remains in complex organic combinations.

PMID- 19867537
TI  - COMPLETE BALANCE STUDIES OF NITROGEN, SULPHUR, PHOSPHORUS, CALCIUM, AND MAGNESIUM
      IN INTESTINAL INFANTILISM.
AB  - In two cases of infantilism there was poor absorption from the intestines of
      nitrogen, sulphur, phosphorus, calcium, and magnesium. The excretion of these
      elements in the urine was low. The excretion of calcium in the urine was so small
      as to be negligible. The excretion of calcium into the intestines was increased.
      The complete balance experiments showed that while other elements were retained,
      calcium was lost.

PMID- 19867538
TI  - THE EFFECT OF FAT AND OF CARBOHYDRATE DIETS ON THE EXCRETION OF CREATIN IN CASES
      OF RETARDED DEVELOPMENT.
AB  - In two cases of infantilism of the type of Herter, in one case of achondroplasia,
      and in one case of cretinism, creatin was constantly present in the urine and was
      increased in amount when the ingestion of carbohydrates was increased.

PMID- 19867539
TI  - PURE CULTIVATION OF SPIROCHAETA REFRINGENS.
AB  - A strain of Spirochoeta refringens has been obtained in pure culture, and its
      morphological and cultural characteristics have been studied. The strain
      possessed no pathogenicity for rabbits or monkeys. It probably belongs to the
      genus Treponema, but it is easily differentiated from Treponema pallidum,
      Treponema microdentium, and Treponema macrodentium. Its relation to Spirochoeta
      balanitidis and Spirochoeta buccalis is still undetermined.

PMID- 19867540
TI  - EFFECTS ON TITRATIONS OF INEQUALITY OF SENSITIZATION OF CORPUSCLES.
AB  - The absorption of amboceptor by corpuscles is rapid, a considerable amount being
      absorbed in as short a period as fifteen seconds. In the sensitization of
      corpuscles, the amount of amboceptor absorbed by the different corpuscles is not
      uniform, the inequality depending on the time taken in obtaining an even
      distribution of the corpuscles through the diluted immune serum. Amboceptor
      absorption is apparently influenced by the concentration of the corpuscles, being
      more rapid with a 5 per cent. than with a 2 per cent. suspension, and thus the
      stronger concentration is more susceptible to inequality of sensitization from
      variations in the method of activation. In experimental work, it is of importance
      to obtain as equal a sensitization as possible. It is essential that in
      comparative titrations the same method of activation be employed in the several
      titrations, and where possible it is advisable that all the cells used be
      sensitized together in bulk. The results obtained in titrating hemolytic sera and
      complement depend to a considerable extent upon the evenness of sensitization of
      the corpuscles.

PMID- 19867541
TI  - ON THE PRESENCE OF NUCLEASE IN CARCINOMA.

PMID- 19867542
TI  - IMMUNOCHEMICAL STUDIES WITH PEPTONES : I. GENERAL STUDIES WITH PEPTONES AND THE
      IMMUNE HEMOLYTIC SYSTEM.
AB  - The experiments here described indicate that the peptone fractions can alter the
      different blood elements in such a manner as to affect their immunological
      reactions. This power is not possessed by all the peptones equally, either
      qualitatively or quantitatively. If we regard the phenomenon of hemolysis by
      immune serum in the light of a biochemical process, depending upon properties
      inherent in certain constituents of the serum and the red blood cells, the
      experiments described reveal a number of facts concerning the immunochemical
      action of albumoses and peptones. These substances, which depend for their
      separation and identification upon purely physical means, show differences in
      their behavior toward the elements concerned in the production of hemolysis.
      Inagaki (7) has shown that the albumoses can combine with nucleohiston. It is not
      improbable, therefore, that some of the reactions are chemical as well as
      physicochemical in character. Further studies are necessary to determine whether
      the reactions elicited can aid us in the differentiation of the peptone bodies,
      for which at present we possess but few tests. The results, however, are
      suggestive, and may aid in recognizing the presence of these substances in blood
      serum.

PMID- 19867543
TI  - EXPERIMENTAL STUDIES ON THE ADMINISTRATION OF SALVARSAN BY MOUTH TO ANIMALS AND
      MAN.
AB  - Salvarsan in capsule and in solution in doses varying from 0.1 to 0.6 of a gram
      was administered by mouth to seven patients suffering from syphilis. Five
      patients were given full doses of 0.6 of a gram. One patient (case 3) received in
      the aggregate within four weeks 2.4 grams without loss of weight or any
      disturbing effects. An ulcerating gumma of the knee was practically healed after
      a period of five weeks. This was the only patient of the seven, however, in whom
      notable improvement in the cutaneous manifestations followed the administration
      of the drug. This ulceration would probably have healed as soon, or possibly
      sooner, under the influence of mercury and the iodids. From the above
      observations, it would appear that salvarsan administered by mouth up to the full
      dose of 0.6 of a gram, has a perceptible though feeble therapeutic effect on
      cutaneous syphilitic manifestations. We should naturally expect the influence of
      any drug to be more evident in the case of a gumma, in which spirochaetes are
      only sparsely present, than in the secondary syphilides in which the spirochaetes
      are present in enormous numbers. Cutaneous gummata are readily healed at times by
      very small doses of mercury or iodids. It is interesting to note that the
      administration of the full dose of the drug by mouth does not appear to give rise
      to symptoms of systemic arsenical poisoning, unless the vomiting and diarrhea be
      regarded as such. After some of the full dose administrations, there was neither
      vomiting nor diarrhea. As salvarsan contains 34 per cent. of arsenic, these
      patients received the equivalent of five grains of arsenic. In case 3, in the
      course of four weeks the patient took by mouth the equivalent of over twelve
      grains of arsenic, without vomiting or having diarrhea, and with no loss of
      weight or disturbance of health. The urine of this patient was entirely normal.
      It would seem, therefore, that salvarsan is not converted in the gastro
      intestinal tract into an organotropic arsenical compound, and it is possible that
      it may remain practically unchanged.

PMID- 19867544
TI  - THE PRODUCTION OF FOREIGN BODY GIANT CELLS IN VITRO.
AB  - 1. Foreign body giant cells may be produced in vitro by the addition of foreign
      objects such as lycopodium spores and cotton fibers to cultures of chick embryo
      spleen. 2. These giant cells are formed by the fusion of large mononuclear
      wandering cells, probably endothelial cells and pulp cells. Connective tissue
      cells do not take part in their formation. 3. The large giant cells sometimes
      seen spread out over the cover-glass in cultures of chick embryo spleen are
      probably foreign body giant cells, the cover-glass acting as the foreign body.

PMID- 19867545
TI  - ON THE PERMANENT LIFE OF TISSUES OUTSIDE OF THE ORGANISM.
AB  - In two series of experiments made at the end of 1911 and at the beginning of
      1912, new techniques were developed with the view of investigating the problem of
      prolonging indefinitely the life of tissues isolated from the organism. These
      techniques are far from perfect and will doubtless be modified in the future. But
      they have already permitted the establishment of new facts. Fragments of
      connective tissue have been kept in vitro in a condition of active life for more
      than two months. As a few cultures are now eighty-five days old and are growing
      very actively, it is probable that, if no accident occurs, the life of these
      cultures will continue for a long time. In some cases the rate of growth of the
      tissues increased in direct ratio to the age of the culture. Fragments of heart
      pulsated rhythmically at the beginning of the third month of their life in vitro.
      These facts show that experiments made with these or with more perfect techniques
      and followed over long periods of time may lead to the solution of the problem of
      permanent life of tissues in vitro, and give important information on the
      characters acquired by tissues liberated from the control of the organism from
      which they were derived.

PMID- 19867546
TI  - ON ALBUMINOLYSINS AND THEIR RELATION TO PRECIPITIN REACTIONS.
AB  - THE WRITER BELIEVES THAT THE EXPERIMENTS ABOVE RECORDED HAVE DEMONSTRATED THE
      FOLLOWING POINTS: 1. As has been previously shown by other workers, complement is
      fixed by the precipitate formed in the reaction between unformed proteid and its
      homologous antiserum, and it is the precipitate only which fixes, the supernatant
      fluid being devoid of fixing power except to a slight degree in tubes very rich
      in antigen. This latter fixation is probably due to a redissolving of the
      precipitin-precipitinogen complex which, as Gay has shown, does not lose its
      fixing power on resolution. The fixation of complement by mixtures in which
      antigen is so slight in amount that no precipitate is formed may be explained by
      analogy with colloidal reactions in which combination of colloids takes place
      without precipitation unless definite quantitative relations are maintained. 2.
      In contrast to the results above described, precipitating mixtures of bacterial
      antigen and antiserum show complement fixation both by the precipitate and by the
      supernatant fluid. 3. The complement fixation by the supernatant fluid of such
      bacterial precipitin reactions, with the precipitate removed, is, in the presence
      of washed bacteria, equal to that exerted by the same amount of the original
      serum. The complement fixation of the precipitates, here, as in serum-antiserum
      tests, is proportionate to the bulk of the precipitate. 4. The precipitin body is
      not removed from a bacterial antiserum by treatment with washed whole bacteria,
      whereas the cell sensitizer or amboceptor is removed by such treatment. The
      writer believes that the work recorded above justifies Gengou's conclusion that
      an albuminolytic sensitizer is formed in response to immunization with unformed
      proteids. This sensitizer, or amboceptor, is, however, distinct and independent
      of the sensitizer that reacts specifically with either bacterial or other cells.
      It would appear that immunization with unformed proteids calls forth only the
      formation of these albuminolysins, while immunization with cells, in our case the
      typhoid bacillus, calls forth both the cytolytic and the albuminolytic
      sensitizers. The albuminolytic sensitizers are not carried down mechanically with
      the precipitates in the precipitin reactions. We see no reason for not
      considering them identical with the precipitins themselves, bodies which combine
      with the dissolved antigens and, as in other colloidal reactions, lead to
      precipitation when definite quantitative relations are observed. The undiminished
      precipitating value of a bacterial antiserum after considerable amounts of
      bacterial amboceptor have been absorbed out of it, would point against the
      identification of agglutinins with precipitins. However, this question must be
      subjected to further study. It is thus clear that only the cytolytic sensitizer
      can enter into combination with the washed bacterial cell, while it is probable
      that both cytolytic and albuminolytic sensitizer may combine with the dissolved
      ingredients of a bacterial filtrate. Whether or not they combine with the same
      constituent of such an antigen cannot be decided by our experiments.

PMID- 19867547
TI  - THE ALLEGED EXISTENCE OF ADRENALIN (EPINEPHRIN) IN PATHOLOGICAL SERA.

PMID- 19867548
TI  - MALARIAL PIGMENT (HEMATIN) AS A FACTOR IN THE PRODUCTION OF THE MALARIAL
      PAROXYSM.
AB  - The paroxysm of hematin intoxication in the rabbit undoubtedly presents many
      features of striking similarity to the paroxysm of human malaria; still one must
      hesitate to apply such results unreservedly in an attempt to identify the
      causative agent of the malarial paroxysm. When, in addition to the character of
      the paroxysm, we consider the sequence of events in the two instances, the
      analogy becomes so close that it seems impossible to regard the matter as a mere
      coincidence. The injection of hematin, especially in fractional doses, is in a
      measure comparable to the liberation of hematin into the human circulation by the
      malarial parasite. In these experiments, See PDF for Structure both solution and
      finely divided suspensions of hematin have been found equally effective in
      eliciting the phenomena of the paroxysm, and while it seems possible that a
      portion of the malarial pigment might be dissolved in the alkaline human serum,
      such an assumption is probably not essential. It might be objected that the toxic
      action of foreign hematin thus injected into the circulation would probably be
      greater than that of hematin derived from an animal's own blood, but as far as I
      have been able to determine, this objection does not seem valid, as rabbit
      hematin, dog hematin, and ox hematin produce in the rabbit effects that are alike
      in both character and degree. The dose of hematin remains as the one factor to
      which it is possible to attach some degree of uncertainty, but even here the
      author feels that the range of experimental conditions has been kept within the
      bounds of legitimate analogy with conditions existing in the human subject of
      malarial infection. Finally, the most conservative estimate of the value of such
      experiments points strongly to the fact that we have at least a potentially toxic
      substance in the pigment hematin as liberated by the malarial parasite into the
      circulation of the human host. There is also abundant evidence to show that the
      action of hematin is not confined to the paroxysmal phenomena of malaria, but
      that other features of the disease may find their explanation in the action of
      this pigment. For the present, however, it seems advisable to confine the
      discussion to this one phase of the question.

PMID- 19867549
TI  - A BIOCHEMICAL STUDY OF THE PHENOMENA KNOWN AS COMPLEMENT-SPLITTING : FIRST PAPER:
      SPLITTING OF THE COMPLEMENT ASSOCIATED WITH GLOBULIN PRECIPITATION.
AB  - It is generally accepted that complement may be split into a mid-piece and an end
      piece. The mid-piece is thought to be in the globulin fraction, and the end-piece
      in the albumin fraction. The restoration of complement activity by putting
      together the albumin and globulin fractions does not prove, however, that each
      fraction contained a part of the complement, for the albumin fraction can be
      reactivated in the absence of the globulin fraction. Complement-splitting as
      brought about by hydrochloric acid, carbon dioxid, and dialysis, is really an
      inactivation of the whole complement by certain acids or alkalis, either added in
      the free state to the serum, or liberated as a result of the dissociation of
      certain electrolytes. That the whole complement, and not a part only, is present
      in the albumin fraction of the serum can be demonstrated by the removal of the
      inhibitory action of the acid or alkali. This can be effected by the addition,
      not only of alkali or acid, but also of any amphoteric substance. When
      hydrochloric acid, carbon dioxid, or dialysis are employed to produce the
      phenomenon known as complement-splitting, the complement is merely inactivated,
      not split.

PMID- 19867550
TI  - A BIOCHEMICAL STUDY OF THE PHENOMENA KNOWN AS COMPLEMENT-SPLITTING : SECOND
      PAPER: SPLITTING OF THE COMPLEMENT WITHOUT A VISIBLE ALTERATION OF THE PROTEID
      CONSTITUENTS.

PMID- 19867551
TI  - A QUANTITATIVE STUDY OF THE EFFECTS OF ADRENALIN ON THE PUPILS OF RABBITS AFTER
      REMOVAL OF A SUPERIOR CERVICAL GANGLION.
AB  - It has been shown by these experiments that after the removal of one superior
      cervical ganglion of a rabbit, 1/50 of a cubic centimeter of a 1:1,000 adrenalin
      solution (=0.02 of a milligram of adrenalin) per kilo of body weight injected
      intravenously, is practically the minimum amount that will produce in nearly all
      cases a perceptible dilatation of the pupil. In one out of eight animals this
      dose failed to give a definite effect, while in two others the effect was slight.
      Six experiments with injections of 1/50 of a cubic centimeter of adrenalin per
      kilo of body weight gave the following averages: a maximum dilatation of 1.62
      millimeters, which showed the first sign of decreasing in four minutes and had
      disappeared entirely in ten minutes after the injection. Six experiments with
      1/30 of a cubic centimeter per kilo gave the following averages: a maximum
      dilatation of 2.25 millimeters, which began to disappear in eight minutes and had
      entirely disappeared in twenty-eight minutes. For thirteen experiments with 1/20
      of a cubic centimeter of adrenalin per kilo these averages were: a maximum
      dilatation of 3.61 millimeters, a beginning recovery from dilatation in six
      minutes, with complete recovery of the pupil in thirty-seven minutes. With 1/10
      of a cubic centimeter of adrenalin per kilo (eight experiments) the averages
      were: a maximum dilatation of 3.87 millimeters, a beginning recovery in ten
      minutes, with complete recovery of the pupil in forty-five minutes. Finally,
      eleven experiments with 2/10 of a cubic centimeter of adrenalin per kilo gave
      averages as follows: a maximum dilatation of 4.38 millimeters, a beginning
      recovery from dilatation in twenty minutes, with complete recovery only after one
      hundred minutes or more. The time between the injection and the appearance of the
      maximum dilatation of the pupil varied somewhat according to the dose of
      adrenalin. In the series of experiments with 1/50 of a cubic centimeter of
      adrenalin per kilo of body weight the average for this interval was one minute;
      in the series with 1/30, 1/20, and 1/10 of a cubic centimeter the average length
      of this interval was about three minutes, while the experiments with 2/10 of a
      cubic centimeter give us an average for this interval of six and a half minutes,
      with individual instances in which the maximum dilatation was seen only after
      fourteen, seventeen, and twenty-two minutes after the injection. In those animals
      in which the maximum pupil dilatation was especially delayed, there were almost
      always more or less alarming symptoms of general prostration for a short time
      after the injection, and the maximum dilatation appeared as these symptoms
      gradually disappeared. In other words, with an increase in the size of the dose
      of adrenalin, there was a gradual increase in the following: (1) the time between
      the injection and the appearance of the maximum dilatation; (2) the amount of
      dilatation produced; (3) the interval between the injection and the beginning of
      recovery from dilatation; and (4) in the total time between the injection and the
      return of the pupil to its normal size. After removal of the ganglion a certain
      time must elapse before the increase in the sensitiveness develops. During the
      first ten to fifteen hours there is practically no increase in the sensitiveness.
      After eighteen hours a moderate effect can be obtained which rapidly increases so
      that by twenty to twenty-four hours after the removal of the ganglion any given
      dose of adrenalin produces practically as great a dilatation as it will give at
      any later time. The experiments teach us that, on account of the individual
      variation in the degree of dilatation produced by a given dose of adrenin, we may
      not determine with exactness from any given degree of dilatation of the pupil the
      quantity of adrenin injected into the blood stream, and that we can not state
      with absolute exactness either the smallest dose that will constantly cause a
      dilatation, or mention the exact amount of adrenin which will in no case cause a
      dilatation of the pupil. However, the results permit the general statement that
      very small doses of adrenin on entering the circulation cause a fairly prolonged
      definite dilatation of a deganglionized pupil. Since this is true, there are then
      at least two ways in which a rabbit from which one superior cervical ganglion has
      been previously removed may be used for determining qualitatively the amount of
      adrenin present. If, for example, we have a solution which may or may not contain
      adrenin, and upon injecting it obtain a dilatation of the deganglionized pupil
      only while the pupil on the normal side remains unchanged in size, we are
      justified in assuming that the solution contains adrenin. Again, if after
      stimulation of the peripheral end of a splanchnic nerve or other procedure upon
      the animal body under conditions that exclude the possibility of reflex effects,
      a dilatation of the deganglionized pupil results, while its normal mate remains
      unchanged, the assumption is warranted, though not absolutely proved, that some
      adrenin has been thrown into the circulation. This test for the presence of
      adrenin has the advantage over other tests, that the pupil on the normal side
      will always act as a control.

PMID- 19867552
TI  - THE EFFECT OF CERTAIN EXPERIMENTAL PROCEDURES ON THE ISLANDS OF LANGERHANS.
AB  - Although the results of this study have been of a negative character, the
      conclusions that may be drawn from it have an important bearing on the true
      anatomical character of the islands. 1. Neither inanition nor the prolonged
      injection of secretin has any noteworthy effect upon the number, size, or
      structure of the islands of Langerhans in the dog's pancreas. 2. The islands of
      Langerhans in the guinea pig's pancreas are in no way altered in phlorizin
      diabetes. 3. The islands of Langerhans are not formed out of exhausted or
      degenerated acini, but develop from the ducts or acini with which they are often
      in direct continuity.

PMID- 19867553
TI  - PERMANENT INTUBATION OF THE THORACIC AORTA.

PMID- 19867555
TI  - STUDIES ON PNEUMOCOCCUS INFECTION IN ANIMALS : FIRST PAPER.
AB  - In summing up the results of these investigations attention is called in
      particular to the following facts. Dead pneumococcus culture material does not
      contain the active poisons formed in infection by living pneumococci.
      Characteristic lesions are not induced by dead cultures. But substances are
      present in the pneumococcus cells, and especially in culture filtrates free from
      pneumococcus cells, that give rise to an immunity in which the poisons of
      virulent pneumococci are inactive. In immune sera specific agglutinative,
      precipitative, lytic, and opsonic activities are present. But to the action of
      immune sera, virulent pneumococci are singularly insusceptible. This is due
      chiefly to qualities acquired by the organisms during their propagation through
      animals. In the test-tube this insusceptibility is overcome only under
      exceptional conditions which destroy these qualities or neutralize their effects.
      Lysis may be brought about by inhibition of growth, and phagocytosis by loss of
      virulence. In the tissues inhibition of growth and resistance to the poisons of
      the pneumococcus are brought about, but in ways more subtle if less exceptional,
      for both lysis and phagocytosis are active factors in the recovery of certain
      animals from infection.

PMID- 19867554
TI  - A PHYSIOLOGICO-PATHOLOGICAL STUDY OF A CASE OF HEART-BLOCK OCCURRING IN A DOG AS
      A RESULT OF NATURAL CAUSES.
AB  - What is believed to be the first known case of heart-block arising in a dog as a
      result of an ingenerate pathological lesion is here reported. The auriculo
      ventricular dissociation was of that degree known as relatively complete block
      and became apparent on section of the right vagus nerve. Stimulation of the
      peripheral end of the cut vagus failed to inhibit the ventricles, although
      complete inhibition of the auricles occurred. The same results were obtained
      during the ventricular acceleration produced by strophanthin, so that the failure
      of the vagus to inhibit the ventricles is not due to the latter's infrequent
      action, but more probably to a normal lack of direct chronotropic influence upon
      the ventricular muscle. These findings are similar to those obtained by Erlanger
      in experimental heart-block. To small repeated doses of strophanthin injected
      intravenously the heart reacted as follows: (a) irregular slowing of the auricles
      and conversion of the relatively complete into an absolutely complete a-v block;
      (b) a rise in the irritability of the cardiac muscle manifested by a rapidly
      progressing auricular and ventricular frequency, the ventricular frequency
      surpassing ultimately the auricular frequency; (c) complete arrest of the
      auricles, the ventricles continuing at their high rate; (d) sudden fibrillation
      of the ventricles and shortly afterwards arrest in diastole. There were found
      post mortem myxomatous-like thickenings at the free edge of the septal tricuspid
      leaflet and at the attached margin of the posterior aortic leaflet and along part
      of the right anterior aortic leaflet. There was also a grayish patch on the right
      side of the auricular septum above the auriculo-ventricular junction. The
      thickenings at the edge of the valves consisted of dense, circumscribed masses of
      what appeared to be new connective tissue. The same tissue was found pressing
      against the bundle along the greater part of the latter's course. There was
      considerable fatty infiltration of the auricular musculature immediately above
      the bundle and, to a slight extent, of the bundle itself. The fibers of
      communication between the auricular muscle and the node of Tawara were relatively
      few as compared with those of the normal heart. A review of the pathology of
      heart-block is appended, showing the present status of the question, concerning
      the relationship existing between disease of the a-v conducting system and the
      various grades of heart-block.

PMID- 19867556
TI  - STUDIES ON PNEUMOCOCCUS INFECTION IN ANIMALS : SECOND PAPER: ACTION OF IMMUNE
      SERA ON PNEUMOCOCCUS INFECTION.
AB  - From the results of this study of the action of immune sera on pneumococcus
      infection it is evident that immune sera vary greatly in their curative value.
      Immune sera possess protective action, but protective action is not necessarily
      indicative of curative action. Treatment with the serum of normal rabbits may
      prolong the course of pneumococcus infection in the rabbit. This action, however,
      is slight and not always manifest. Sera from animals immunized with dead
      pneumococcus cells which had been washed free from their products, failed to
      exert materially greater curative action than normal sera. Sera from animals
      immunized with culture filtrates free from pneumococcus cells possessed, in some
      instances, a slight curative value, but often this curative action was not
      apparent. In animals actively immunized, however, the presence of an immunity to
      culture filtrates was readily demonstrated. In the immunity produced by
      injections of dead culture material the strength was not sufficiently exalted for
      the sera to possess a practical curative value. It was only after immunization
      with virulent living cultures that the blood serum acquired marked curative
      action. After pneumococcus infection in the rabbit had become established,
      treatment with this serum induced crisis and cured the animals. From the results
      of the study of the mechanism of recovery it is evident that, despite the fact
      that virulent pneumococci are singularly insusceptible to the action of immune
      sera in the test-tube, pneumococcus infection nevertheless conforms to the
      general law of infection. Diphtheria and tetanus organisms give rise to powerful
      toxins, but the parasitism of these organisms is slight and their development is
      localized. Diseases produced by these organisms are toxemias and neutralization
      of their toxins by antitoxin puts an end to the disease. The pneumococcus gives
      rise to toxic substances which are less active or are active only in the body
      tissues, but the parasitism of this organism is marked and its development is
      rarely localized. Nevertheless, the manifestations of the disease arise from the
      action of the bacterial poisons on the tissues. The neutralization of the
      pneumococcus poisons by immune serum puts an end to the symptoms of the disease,
      but the pneumococci survive as harmless parasites until destroyed by lysis or
      phagocytosis. The neutralization of the pneumococcus poison may take place
      suddenly and completely as in crises; or, it may be incomplete with exacerbations
      of infection, as in lysis. Crisis, as it occurs in the lobar pneumonia of man and
      in the bacteriemia of the rabbit, is simply one phase of recovery, and recovery
      does not differ fundamentally, whether it is sudden and complete as in crisis, or
      incomplete and prolonged as in lysis, or whether the pneumococci are destroyed by
      lysis extracellularly as in the rabbit, or intracellularly as in the phagocytosis
      of the dog and man. Since the recovery of animals from pneumococcus infection
      differs in no essential from that of man, since the unaided protective mechanism
      of man as compared with that of susceptible animals is exceptionally efficient,
      and since it is possible by treatment with sera from animals highly immunized
      with living cultures of virulent pneumococci to cure pneumococcus infection in
      the most susceptible animals, it is difficult to conceive of the infection in man
      failing to yield similarly to the administration of such sera.

PMID- 19867558
TI  - EXPERIMENTAL BRONCHOPNEUMONIA BY INTRABRONCHIAL INSUFFLATION.
AB  - When intrabronchial insufflation of pure cultures of the streptococcus or of the
      influenza bacillus is properly carried out, it produces without fail a pneumonic
      lesion. This lesion is similar in its nature to the one known in human pathology
      as bronchopneumonia, and differs materially from the pneumonic lesion produced
      experimentally by the intrabronchial insufflation of pure cultures of the
      pneumococcus. Considering the fact that none of the dogs used in the experiments
      with the pneumococcus and none of those used in the present investigation were
      selected or prepared in any way, the conclusion seems to be unavoidable that the
      proper invasion of the microorganism is the determining factor in the development
      of pneumonia, the condition of the animal being only a minor element in this
      regard. Furthermore, since different organisms introduced in the same way and
      under conditions which are apparently the same produced distinctly different
      pneumonic lesions in animals of the same species, the further conclusion presents
      itself that the different types of pneumonia are produced by specifically
      different bacteria. However, further investigation may show that the differences
      in the nature of the lesion are due rather to the degree of virulence of the
      causative microorganism than to differences in the species; that is, that
      different lesions may possibly be produced by organisms of the same species,
      provided they possess different degrees of virulence. Further experimentation may
      also show that the condition of the animal and of the affected organ which, in
      the onset and development of the pneumonic disease, is, perhaps, unimportant, may
      be the leading factor in determining the course and outcome of the disease.

PMID- 19867557
TI  - THE VASODILATOR AND VASOCONSTRICTOR PROPERTIES OF BLOOD SERUM AND PLASMA.
AB  - 1. In plasma there exists a vasodilator substance specific for the vessels of the
      kidney. 2. This substance is a proteid of the albumin class and is precipitated
      by boiling and by alcohol. 3. It is present also in the serum. 4. It acts
      directly on the muscle coats of the arteries. 5. The process of clotting of the
      blood liberates a constrictor substance that acts on the renal vessels and also
      on the vessels of the limb. 6. This constrictor substance is not a proteid; it
      resists boiling, is soluble in alcohol, and acts directly on the muscle coat.

PMID- 19867559
TI  - SOME OBSERVATIONS OF THE THORACIC DUCT LYMPH AFTER INJECTION OF OIL OF TURPENTINE
      INTO THE PERITONEAL CAVITY OF THE DOG.
AB  - Injection of oil of turpentine into the peritoneal cavity of a dog calls forth
      immediately an exudate of fluid from the surrounding tissues. The amount of fluid
      reaches the maximum on the third day and has practically disappeared on the fifth
      day. The cell content of this fluid is very small at first, but increases
      rapidly. The type of the predominating cells also changes. In the early exudate
      the small mononuclear cells are numerous and the large mononuclears few. Later
      the number of large mononuclear cells is increased and ultimately the
      polymorphonuclear cells preponderate. Various forms of atypical cells also occur.
      Much of the fluid and many of the cells are removed by way of the thoracic duct.
      The counts of the cells in the thoracic duct and the estimates based on these
      indicate that the duct does not remove all of the fluid or cells from the
      peritoneal cavity. Much fluid is probably taken back directly into the blood, as
      are many of the cells. Some of the cells make their way to the lymph nodes, while
      many perhaps undergo complete autolysis in the serous cavity. The
      polymorphonuclear cells do not enter the thoracic duct in great numbers.
      Examination of the lymph from the thoracic duct in the case of my dogs showed the
      types of cells that are usually found there. The variation in small mononuclear
      cells is so related to the cell content of the peritoneal effusion as to indicate
      that the supply in the blood is maintained from this source. The form and
      staining qualities of the cells indicate that many of the small mononuclear cells
      are returned to the thoracic duct. The ratio of polymorphonuclear cells present
      in the lymph bears no definite relation to the other features of the process. The
      transitional cells were increased in number and in their ratio to other cells.
      The increase in the transitional types accompanies an increase in large
      mononuclear cells and a decrease in small mononuclears. None of the atypical
      forms of cells found in the effusion were seen in the lymph. The number of
      eosinophils is without apparent relation to the other features of the process. No
      polymorphonuclear cells containing the pigment injected were found in the lymph
      of the thoracic duct, and the number of mononuclear cells containing pigment was
      small. Much pigment was deposited in the lymph nodes. Detailed and definite
      conclusions as to the relation between the cells of the lymph and those of the
      effusion cannot be arrived at satisfactorily without repeated observations on the
      same animal. Dr. Warthin examined many of the smears from these cases and
      frequently controlled the conclusions regarding the various types of cells. Dr.
      P. F. Morse assisted me frequently with the operative procedures and with the
      routine counting of the cells.

PMID- 19867560
TI  - CHANGES IN THE TISSUE SURROUNDING A GROWING TUMOR AND THE SIGNIFICANCE OF THE
      "PRECANCEROUS STATE.".
AB  - An analysis of the results of the experiments reported in this investigation
      shows that the changes so frequently observed in tissues surrounding a growing
      tumor may be caused by different conditions. The development and growth of a
      malignant tumor depends upon a local interaction between tumor cells and organ
      cells. When the cells of a normal organ are capable of inhibiting tumor growth,
      then an impairment of the normal state of the parenchymatous cells of this
      particular organ is essential for the growth of the tumor. This "precancerous
      state" does not consist primarily of an inflammatory change in the adjacent
      connective tissue, as Ribbert and his followers maintain, but in a degeneration
      of the parenchymatous cells of the organ. If, in another instance, the cells of
      the normal organs are unable to inhibit the proliferation of the tumor cells,
      then no preparation of the cells of the organ for the tumor is necessary, i. e.,
      no "precancerous state" is needed to enable the tumor to grow. On the other hand,
      the proliferating tumor cells injure normal cells, either mechanically or
      chemically, producing a condition that appears on superficial examination like
      that described as the "precancerous state." In reality, however, this condition
      is the resultant effect of the tumor growth and may be more correctly designated
      the "postcancerous state." In these conditions, then, von Hansemann's explanation
      of the phenomenon, and not Ribbert's, seems to be the correct one. Of still
      greater importance is the fact demonstrated in the last series of experiments;
      namely, that the general condition of resistance or immunity to cancer growth
      exerts a greater influence on the organism of the animal than any of the local
      conditions described above. The local resistance of a testicle to tumor growth in
      a generally susceptible animal may be overcome, but if an animal is made
      generally immune to the growth of cancer, neither the animal as a whole nor a
      single organ or tissue in it can be made susceptible to the growth of the tumor.

PMID- 19867561
TI  - TUMOR INOCULATION INTO ORGANS AND THE ANALOGY BETWEEN HUMAN CANCER AND THE TUMORS
      OF WHITE MICE AND WHITE RATS.
AB  - The analysis of the experiments described above indicates that tumors of the
      white rat or white mouse inoculated into parenchymatous organs acquire a
      different biological character from those inoculated subcutaneously. The latter
      are a great deal more benign in their behavior than human cancer or spontaneous
      tumors in the same species of animals. Tumors inoculated into organs, on the
      other hand, are quite identical in their biological behavior with the malignant
      tumors of animal and man. A conclusion must then be drawn, even a priori, that
      the method of inoculation into organs is a very important aid in the experimental
      investigation of cancer. It is true that the method is a great deal more
      complicated and time-consuming than the ordinary subcutaneous inoculation. The
      subcutaneous method is satisfactory for a number of cancer problems. One of these
      is the study of general susceptibility and resistance of the organism of the host
      to the inoculation of the tumors, and this is a subject of paramount importance
      in cancer research. On the other hand, the investigations of the writer (10) have
      shown that an animal may be susceptible to a subcutaneous inoculation of a
      certain tumor and resist the inoculation of the same tumor into the testicle.
      Undoubtedly this method of inoculation will reveal the existence of a number of
      other phenomena. The discovery of specific therapeutic measures is certainly the
      greatest problem in cancer research. A great deal of work has been done already
      on the subject, and the latest investigations of Wassermann on the chemotherapy
      of experimental tumors seem to be of great promise. But here also the therapeutic
      methods must be tried on animals in which the inoculations of tumor cells have
      been made into parenchymatous organs before the growths thus treated will have
      any analogy to human cancer. In this connection one must bear in mind the fact
      that all the empirical so-called specific cancer remedies, which are continually
      being devised, are usually successful in treating localized skin cancers and fail
      utterly in the malignant growths of the internal organs. It is comparatively easy
      to produce a localized necrosis and softening in a circumscribed growth of the
      skin and subcutaneous tissue, but whether the same result will be produced on a
      diffuse and better nourished tumor growing inside of a parenchymatous organ
      cannot be decided a priori. To determine this it is necessary to have
      experimental proof on animals in which the tumor was inoculated into organs.

PMID- 19867562
TI  - PURE CULTURES OF CELLS.
AB  - In experiment I a group of ameboid cells was isolated from a culture of cardiac
      muscle sixty-three days old, and cultivated in plasma. After several passages,
      they formed a dense tissue from which ameboid cells radiated. The culture was
      divided into two parts. The part cultivated in plasma alone kept its
      morphological characters and continued to produce ameboid cells. The part
      cultivated upon silk in plasma became modified; the cells lost their ameboid
      characters, and were transformed into large elongated cells which were united in
      chains, or interlaced to form a network. In experiment II the round cells taken
      from a culture of connective tissue seventy-four days old multiplied rapidly.
      They transformed themselves into elongated cells and produced, after a few
      passages, a mass of dense connective tissue. From the tissue a large number of
      elongated cells were constantly growing. In both experiments the tissues
      originated from the ameboid or round cells extirpated from cultures that were
      sixty-three and seventy-four days old respectively. These cultures were still
      growing actively thirty and forty days later; that is, more than one hundred days
      after the extirpation of the original fragments from the organism. These
      experiments show that from old cultures it is possible to isolate and propagate
      cells that belong to a definite type. A tissue, formed by a pure strain of cells,
      can be obtained in this way, and this new method may be of value in cytological
      investigations.

PMID- 19867563
TI  - THE INFLUENCE OF ISOAGGLUTININS ON THE FINAL RESULTS OF HOMOPLASTIC
      TRANSPLANTATIONS OF ARTERIES.
AB  - The results in the group in which there was interagglutination differ in no
      striking way from those obtained in the group in which there was no
      interagglutination. It may be concluded, therefore, that the presence of
      isoagglutinins is of no importance for the final results of the homoplastic
      transplantation of arteries. From the conflicting evidence of the survival of
      muscular fibers in one case and their disappearance in many other cases, it may
      be concluded further that between animals of the same species there are unknown
      biological differences that prevent, in most instances, the survival of
      homoplastic transplanted arteries, although a survival does occur in some cases.

PMID- 19867564
TI  - STUDIES IN GLYCOSURIA : SECOND PAPER: GLYCOSURIA FOLLOWING ANESTHESIA PRODUCED BY
      THE INTRAVENOUS INJECTION OF ETHER.
AB  - 1. By introducing intravenously into dogs a solution of 5 per cent. ether in
      normal saline (0.9 per cent.), a satisfactory surgical anesthesia can be
      produced. 2. Associated with this anesthesia a glycosuria occurs in healthy adult
      dogs fed on a meat diet. 3. Normal saline (0.9 per cent.) introduced in exactly
      the same manner does not cause a glycosuria. 4. The glycosuria is, in general,
      associated with a hyperglycemia. 5. The glycosuria does not make its appearance
      until the condition of anesthesia has been produced. 6. The intravenous method of
      producing anesthesia employed in our studies eliminates largely the factor of
      asphyxia. 7. Consequently by this mode of administration ether may cause
      glycosuria without asphyxia. 8. The addition of ether to normal saline (0.9 per
      cent.) solution modifies the property of the latter to produce diuresis. 9.
      Associated with the intravenous administration of both the saline and the ether
      saline solutions there occurs a rise of body temperature.

PMID- 19867565
TI  - TREPONEMA MUCOSUM (NEW SPECIES), A MUCIN-PRODUCING SPIROCHAETA FROM PYORRHEA
      ALVEOLARIS, GROWN IN PURE CULTURE.
AB  - 1. A mucin-producing spirochoeta has been obtained in pure culture from a case of
      pyorrhea alveolaris. This organism is an independent species of the genus
      Treponema and, as it is recognized for the first time, I propose for it the name
      Treponema mucosum. 2. Morphologically the mucosum is difficult to separate from
      the pallidum and microdentium, but, through its biological properties and animal
      reactions it is easily differentiated from all the rest of the spirochoetae. 3.
      The mucosum is not parasitic in the strict sense of the term, but exerts a
      certain pyogenous action when the tissue has been so injured by foreign
      substances as to enable it to survive. 4. The strong fetid odor in the discharge
      from pyorrhea alveolaris is due, at least in part, to the presence of the mucosum
      in the affected tissue.

PMID- 19867566
TI  - THE PURE CULTIVATION OF SPIROCHAETA DUTTONI, SPIROCHAETA KOCHI, SPIROCHAETA
      OBERMEIERI, AND SPIROCHAETA NOVYI.
AB  - 1. A method for the pure cultivation of Spirochoeta duttoni, Spirochoeta kochi,
      Spirochoeta obermeieri, and Spirochoeta novyi is described in this paper. In
      vitro these strains reach their maximum growth after seven, eight, or nine days
      at 37 degrees C. For their multiplication they require the presence of a piece of
      fresh sterile tissue and a body fluid capable of forming a loose fibrin with the
      tissue. The presence of some oxygen seems indispensable for their growth, since
      they fail to grow in an atmosphere of hydrogen or in vacuo. No growth was
      obtained at room temperature. 2. From cultures that show a good growth
      subcultures can be made and the growth can be kept up in this way for many
      passages. 3. The pathogenicity of these organisms is not lost by cultivation,
      although there is a tendency for the virulence to become attenuated after growth
      in vitro has continued for a long time. 4. Longitudinal division has been
      observed and was followed under the dark-field microscope in fresh preparations
      from cultures. It occurs in all the species irrespective of the length of the
      organism. Transverse division seems also to occur, but I have not yet observed
      the entire process.

PMID- 19867567
TI  - A METHOD FOR CULTIVATING TREPONEMA PALLIDUM IN FLUID MEDIA.
AB  - 1. A method is described for obtaining pure cultures of Treponema pallidum and
      allied species of spirochaetae in fluid media. 2. The principle of the method is
      based upon the superposition of a favorable culture medium upon a less favorable
      one. 3. The method here described is not suited to the growth of spirochaetae
      when they are admixed with contaminating bacteria.

PMID- 19867568
TI  - THE PREVENTIVE ACTION OF DIPHTHERIA ANTI-TOXIN IN SERUM-SENSITIZED RABBITS.

PMID- 19867569
TI  - THE SELECTIVE BACTERICIDAL ACTION OF GENTIAN VIOLET.

PMID- 19867570
TI  - THE NATURE OF THE BACTERICIDAL SUBSTANCE IN LEUCOCYTIC EXTRACT.
AB  - 1. The bactericidal agent extracted from horse leucocytes is apparently
      precipitated quantitatively by full saturation with ammonium sulphate. 2. The
      bactericidal agent is apparently precipitated by absolute alcohol, and is not
      rendered insoluble by a short contact with alcohol. The agent resembled in this
      feature certain enzymes which can be isolated and purified by alcoholic
      precipitation.

PMID- 19867571
TI  - PURE CULTIVATION OF SPIROCHAETA PHAGEDENIS (NEW SPECIES), A SPIRAL ORGANISM FOUND
      IN PHAGEDENIC LESIONS ON HUMAN EXTERNAL GENITALIA.
AB  - 1. A hitherto undescribed spiral organism has been isolated in pure culture from
      a case of mild phagedenic ulcer on the external genitalia of a woman. For this
      organism the name Spirochoeta phagedenis is proposed. 2. Spirochoeta phagedenis
      is a strict anaerobe and grows in the presence of fresh tissue in ascitic agar.
      It produces no apparent change in the media, but a somewhat offensive odor
      develops in the culture tube. 3. Spirochoeta phagedenis incites a slight
      inflammatory reaction in the skin of a Macacus rhesus monkey and in the skin and
      testicles of rabbits. 4. Its etiological relation to the phagedenic lesions on
      the external genitalia has not yet been determined.

PMID- 19867572
TI  - STUDIES IN FERMENT ACTION : II. THE EXTENT OF LEUCOCYTIC PROTEOLYSIS.
AB  - This work proves that the proteolytic action of leucocytes is not a simple
      cleavage by one ferment. There are present two proteases, one acting in an
      alkaline medium and the other in an acid medium. This confirms Opie's work. In
      the leucocytes there was found in addition an ereptic ferment which is capable of
      acting in an acid or alkaline medium. Since this action is lost by heating to 70
      degrees C., and by drying and keeping the leucocytes, it probably represents a
      ferment which acts on the digestion products of the two proteases. Analogy with
      other ferments in the body confirms this opinion.

PMID- 19867573
TI  - A COMPARISON OF SIMULTANEOUS POLYGRAPH AND MICROGRAPH TRACINGS.
AB  - FROM A STUDY OF THE ACCOMPANYING TRACINGS WE MAY CONCLUDE THAT: 1. The delicate
      mechanism of the micrograph registers the movements in the heart and blood
      vessels more accurately than does the polygraph. 2. The inertia of the polygraph
      lever and diaphragm distorts the tracing. The difference between the results
      obtained with the two instruments is shown by the records made simultaneously
      with the micrograph and the polygraph. 3. The micrograph is particularly useful
      for recording heart sounds. Some records illustrating this are shown. We are
      directing especial attention to this and will report the results in a subsequent
      paper. 4. While the micrograph will not supersede the polygraph or
      electrocardiograph, we feel that it has distinct possibilities as a clinical
      instrument.

PMID- 19867574
TI  - A STUDY WITH THE ELECTROCARDIOGRAPH OF THE MODE OF DEATH OF THE HUMAN HEART.
AB  - In four of the seven cases the ventricles remained active from one and a half to
      eighteen minutes after the electrocardiograms failed to show evidence of
      auricular activity. In two cases the auricles outlasted the ventricles and in one
      case only did the auricles and ventricles stop apparently at the same time.
      Complete dissociation occurred three times. Some delay in the conduction time was
      seen in five of the seven cases. In two cases the auricles ceased to beat before
      evidence of impaired conduction appeared. There was always marked slowing; the
      slowest independent ventricular rates varied from 13.6 to 47.0. The slowest rates
      at which the auricles beat regularly varied from 20 to 65 per minute. There was
      never evidence of auricular fibrillation, although in two cases the
      electrocardiograms give fairly conclusive evidence that ventricular fibrillation
      occurred. The ventricles reestablished a regular rhythm after a short period of
      ventricular fibrillation in one case, while in the other but one ventricular
      contraction occurred after the appearance of fibrillation. Characteristic changes
      in the ventricular complex of the electrocardiograms occurred in all the records.
      They consisted of a gradual fusion of the R- and T-waves, forming, when the
      fusion was complete, a large rounded or peaked wave. In some cases the identity
      of the two waves was not entirely lost. In spite of the marked change in shape of
      the ventricular complexes, there was often but little change in their duration.
      In some cases the ventricular systole was shortened at the end, while in others
      it was prolonged. The change in the form of the ventricular electrical complex
      indicates that the course of the stimulus and the manner of the contraction of
      the muscle were abnormal. The fact that the R-wave became gradually prolonged
      suggests that the conduction of the stimulus through the ventricular walls became
      delayed as the heart died. The fact that after death there is a continuation of
      cardiac muscular activity sufficient to cause a difference in electrical
      potential between the two sides of the body does not necessarily mean that a
      ventricular systole in the sense of muscular shortening takes place. It has been
      observed experimentally that well defined electrical complexes may be caused by
      cardiac activity which cannot be seen or recorded graphically. As the duration of
      the ventricular complexes characteristic of the dying heart usually does not
      differ markedly from the duration of the complexes before clinical death, it
      seems probable that the entire musculature of the ventricles participates in the
      contraction; as definite shortening, or at least a marked change in duration,
      would be expected if only a part of the ventricular musculature participated in
      the activity which produced the complex.

PMID- 19867575
TI  - NITROGEN AND NUCLEIN METABOLISM IN GOUT.
AB  - Thus, our conclusions harmonize with those of Brugsch and Schittenhelm in so far
      as they are concerned with the nuclein metabolism. They add, however, the
      observation that the elimination of nitrogenous substances of protein origin has
      a protracted character, and that the oxidation of as simple a substance as
      asparagin proceeds at a subnormal rate. The most striking peculiarity observed in
      our patient was the very imperfect elimination of ingested urea when the patient
      was placed on a diet containing only six grams of nitrogen per day, and a much
      more complete elimination when the diet contained thirteen grams of nitrogen.

PMID- 19867576
TI  - THE DURATION OF IMMUNE BODIES IN THE BLOOD AFTER ANTITYPHOID INOCULATION.
AB  - In this series of twenty-four persons inoculated with antityphoid vaccine, the
      immune bodies in the blood reached their height within two months after the first
      inoculation, or one month after the third, then fell rapidly within the next two
      months. Only nineteen of the cases could be followed longer, and eight of these
      were negative for bactericidins within ten months after inoculation, and fifteen
      were negative after thirteen months. Only one serum reacted in a dilution of 1 to
      1,200 at the end of thirteen months. The addition of lecithin to the vaccine did
      not influence the local reaction after inoculation, nor did it appreciably affect
      the formation of immune bodies to the typhoid bacillus.

PMID- 19867577
TI  - POST-HEMORRHAGIC ANEMIA.
AB  - In rabbits and cats in which a hemorrhagic anemia has been produced, the
      hemoglobin is regenerated much more slowly than the red corpuscles, but the
      index, relative to the red corpuscles, never rises above one. The resistance of
      the corpuscles is not increased. In erythrocytes developing in the bone marrow,
      the nucleus of the erythroblasts seems to lose its chromatin, but is apparently
      not extruded. Punctate basophilia of the erythrocytes is a common feature and
      seems to result from a diffusion of nuclear chromatin through the cell.
      Extramedullary myeloid metaplasia is generally slight, but in moderately severe
      and long continued anemia from bleeding it may be very extensive. Lipemia usually
      occurs when the blood is reduced below a certain limit. The greater part of the
      fat in the serum can be extracted with ether and is stained by osmic acid.
      Extensive fatty infiltration of the organs may occur and also widespread necrosis
      in the central parts of the liver lobules. Pigmentation of the internal organs is
      usually only slight, but may be considerable, particularly in the spleen.
      Although there are minor differences, all the essential features of anemia
      produced by toxins can be reproduced by hemorrhage.

PMID- 19867578
TI  - A STUDY OF COMPLEMENT FIXATION IN SYPHILIS WITH SPIROCHAETA CULTURE ANTIGENS.

PMID- 19867579
TI  - THE RETENTION OF FOREIGN PROTEIN BY THE KIDNEY : A STUDY IN ANAPHYLAXIS.
AB  - Extracts of the kidneys of normal rabbits prepared one, two, three, and four days
      after the intravenous injection of egg-albumin and horse serum have the power to
      sensitize guinea pigs to a second injection of these proteins. The sensitization
      by first and second day extracts was constant and intense, that by the third day
      extracts was less marked and sometimes was not evident, and that by the fourth
      day extracts was only occasional, and when present was always weak. Comparative
      studies of the power of the blood, liver, and kidney to sensitize, indicate that
      this sensitization depends on the content of foreign protein in the circulating
      blood and not upon its accumulation or fixation in the tissues of an organ. This
      opinion is supported by other experiments in which the sensitizing power of the
      blood and of the extracts of unwashed kidneys was compared with the sensitizing
      power of extracts of washed kidney. The weak sensitizing power of washed kidney
      extract is taken as evidence that foreign proteins of the kinds used are not held
      in the tissues of the kidney, and if these results may be applied to nephrotoxic
      proteins, it follows that nephritis is not due to selective and persisting
      fixation of a protein by the renal cells, but is due to the action of such
      protein merely during the process of its elimination. In experimental acute
      nephritis of the type due to uranium nitrate, the power of sensitization to egg
      albumin is prolonged for twenty-four hours, and in the chrornate type for forty
      eight hours, thus indicating that in nephritis, of the acute type at least, the
      elimination of a foreign protein is delayed. Attempts to study by the same
      methods the elimination of vegetable and bacterial proteins have failed.

PMID- 19867580
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : I. REACTIONS TO HEMOLYTIC SERUM AT VARIOUS INTERVALS AFTER
      SPLENECTOMY.
AB  - This investigation brings out three points. 1. During the first three or four
      weeks after splenectomy hemoglobinuria due to hemolytic serum was not followed by
      jaundice. 2. One month and more after splenectomy the red cells had an increased
      resistance to hemolysis. 3. Three and a half months after splenectomy and even
      later, jaundice occasionally occurred spontaneously. Attempts to explain these
      three phenomena have been based on the following possibilities: (1) that some
      function of the spleen is essential for the degradation of hemoglobin or for the
      elaboration of its derivatives; (2) that there is some interrelation between the
      spleen and the blood-forming organs or between the spleen and the blood
      disintegrating mechanism, or perhaps both interrelations exist; (3) that there is
      a disturbance of the hemolyzing or bile-forming function of the liver dependent
      on the blood changes following splenectomy. This multiplicity of problems and
      likewise of possible explanations has rendered the presentation of the
      explanatory work in one communication extremely difficult. In the interests of
      clearness, therefore, the various phases are dealt with in separate papers.

PMID- 19867581
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : II. THE RELATION OF HEMOGLOBINEMIA TO HEMOGLOBINURIA AND JAUNDICE IN
      NORMAL AND SPLENECTOMIZED ANIMALS.
AB  - The results of this study may be stated as follows. 1. Rapid injection of more
      than 0.06 of a gram per kilo of hemoglobin intravenously into a normal animal is
      followed by the appearance of hemoglobin in the urine (pelvis of kidney) within
      eight to ten minutes. 2. After rapid injection of more than 0.012 of a gram per
      kilo per minute of hemoglobin, 16 to 36 per cent. of the total amount, if this
      equals 0.25 of a gram per kilo, is eliminated in the urine and is accompanied by
      choluria. 3. If the injection of not more than 0.35 of a gram per kilo is made
      slowly (less than 0.01 of a gram per kilo per minute), the amount eliminated in
      the urine is only 2.33 to 9.5 per cent. of the total amount injected, and
      choluria does not occur. 4. The concentration of free hemoglobin in the blood
      which constitutes the threshold value of the kidneys for hemoglobin is
      approximately 0.06 of a gram of hemoglobin per kilo of body weight. When about
      this concentration is reached, hemoglobin appears in the urine. 5. The amount of
      hemoglobin per kilo of body weight which, after rapid injection, may be retained
      without jaundice, is approximately 0.18 of a gram. When 0.22 or 0.23 of a gram is
      retained bile pigments appear in the urine. The threshold of the liver for
      jaundice in point of hemoglobin saturation lies, therefore, between 0.18 and 0.22
      of a gram per kilo of body weight. With slow injections a greater amount may be
      retained without choluria. 6. The absence of the spleen does not alter greatly
      the percentage of hemoglobin eliminated by the kidney, nor does it raise the
      threshold of the liver for jaundice. 7. In the presence of jaundice, either
      hemolytic or obstructive, the amount of hemoglobin retained by splenectomized
      animals is slightly diminished and that eliminated by the kidneys is
      correspondingly increased. Upon these data may be based the following explanation
      of the mechanism by which free hemoglobin is removed from the blood serum.
      Hemoglobin is not removed by the kidney until its concentration in the blood
      serum reaches a certain level (0.06 of a gram of free hemoglobin per kilo of body
      weight). This constitutes the threshold value of the kidneys for hemoglobin and
      when it is reached hemoglobin appears in the urine. When the concentration is
      lower, hemoglobinuria ceases; at the same time, however, the liver, and possibly
      other tissues, take up hemoglobin as soon as mere traces are present in the serum
      and they continue this removal whether the renal threshold is exceeded or not.
      The two processes go on simultaneously, the rate of removal, when the renal
      threshold is exceeded, being for the kidneys 17 to 36 per cent., and for the
      liver and other tissues 64 to 83 per cent, of the total amount introduced. The
      hemoglobin which is removed by the liver is transformed into bile pigments. If
      the amount reaching the liver is small and is received slowly, the amount of bile
      formed is not increased above the excretory capacity of the liver, and it is
      removed by the bile passages without the occurrence of choluria. This is shown in
      our experiments in which injections of hemoglobin were made more slowly than 0.01
      of a gram per kilo per minute. On the other hand, if the hemoglobin is taken up
      by the liver rapidly and in large amounts, the bile capillaries are overtaxed and
      the bile cannot be rapidly removed, but is reabsorbed into the blood, and
      choluria develops. If this theory is correct we have an explanation of those
      instances of blood destruction in man characterized by jaundice, but not
      accompanied by hemoglobinuria. In a slow, gradual destruction of the red blood
      cells, the liver removes the hemoglobin from the serum so rapidly that the
      concentration of hemoglobin in the serum does not reach the threshold value of
      the kidneys and hemoglobinuria, therefore, cannot occur. The constant absorption
      of large amounts of hemoglobin by the liver and the increase in bile formation
      which results does, however, overtax the bile passages and jaundice occurs. In
      the same way may be explained the continuance of jaundice after the disappearance
      of a transient hemoglobinuria. A rapid destruction of a large amount of blood
      raises the concentration of hemoglobin in the serum so quickly that the threshold
      value of the kidney is quickly exceeded and hemoglobin appears in large amounts
      in the urine. When an amount of hemoglobin sufficient to reduce the concentration
      of the serum below the threshold value of the kidney has been removed, a
      considerable amount of hemoglobin may still remain in the serum, and it is the
      slow elimination of this through the liver that causes the choluria to continue.
      The demonstration that the absence of the spleen has no important influence on
      the elimination of hemoglobin by the kidney, on its transformation into bile
      pigments, or on the removal of such pigments, is of interest in connection with
      an observation made in the first paper of this series. This was concerning the
      frequent failure of jaundice to follow the administration of hemolytic serum
      during the early period following splenectomy. Among the possible explanations
      was the suggestion that the spleen is in some way concerned in the disintegration
      of free hemoglobin or in the elaboration of its derivatives. The present
      investigations demonstrate that such an explanation is without experimental
      basis, though it does not controvert the possibility of the spleen being
      concerned in liberating hemoglobin from the red cells and suggests that the
      failure of jaundice is due to some other factor or factors. Evidence to indicate
      that the changes in the blood that follow splenectomy are important factors is
      offered in the third paper of this series.

PMID- 19867582
TI  - FIBRILLATION OF THE AURICLES: ITS EFFECTS UPON THE CIRCULATION.
AB  - When the auricles fibrillate, the following effects are observed. 1. The arterial
      blood pressure may rise, fall, or remain stationary. Usually it falls. If it
      falls, it generally rises again towards or to the initial pressure. 2. The venous
      pressure changes are the reverse of the arterial. 3. The intestinal volume and
      the cardiac output changes are in the same direction as those of arterial blood
      pressure. 4. From these observations it may be concluded that the peripheral
      circulatory effects are purely passive. 5. The volume of the heart decreases
      except in instances where there is reason to believe that the circulation is
      failing. All the changes described in the foregoing paragraphs, and also the
      variations in blood pressure reactions which occur from time to time, are
      attributable to alterations in the rate of ventricular contraction. Similar,
      though perhaps less profound changes, are seen when the heart rate accelerates in
      like degree in response to regular induction shocks.

PMID- 19867583
TI  - STUDIES UPON THE CHARACTERISTICS OF DIFFERENT CULTURE MEDIA AND THEIR INFLUENCE
      UPON THE GROWTH OF TISSUE OUTSIDE OF THE ORGANISM.
AB  - 1. There is a great difference between embryonic and adult tissue as far as their
      growth outside of the organism is concerned. Adult tissue grows only in plasma.
      Embryonic tissue grows also very well in serum and serum plus agar. In Ringer's
      solution and in Ringer's solution plus agar no growth occurs, whether embryonic
      or adult tissue is employed; survival and emigration of cells are seen to some
      extent. 2. For the growth of connective tissue cells of chick embryo, unheated
      homogenic serum is a better culture medium than heated serum. The growth of
      epithelial cells is not thus influenced. 3. Heated heterogenic serum is a better
      culture medium for growth of embryonic connective tissue cells than unheated. 4.
      There is an inverse ratio between the hemolytic power of heterogenic sera and the
      extent of growth of tissue in them. This inverse ratio is not found in
      heterogenic plasmas.

PMID- 19867584
TI  - THE RELATIVE PREVALENCE OF HUMAN AND BOVINE TYPES OF TUBERCLE BACILLI IN BONE AND
      JOINT TUBERCULOSIS OCCURRING IN CHILDREN.
AB  - The all important point revealed by the investigation is the fact that a large
      proportion of bone and joint tuberculosis occurring in children in Edinburgh owes
      its origin to infection by the bovine bacillus. The bovine bacillus is introduced
      into the system practically by one route only, that of ingestion, and the medium
      with which it is ingested is cow's milk. It is not my intention to criticize in
      any way the existing conditions of milk supply. I have furnished proof of what is
      actually occurring and no one will deny that the evil is a remediable one. In
      those cases in which the human bacillus was present, a considerable proportion
      showed a definite history of pulmonary tuberculosis affecting a co-resident, and
      every fact went to prove that the infection had been a direct one from patient to
      child. A complete distinction can be drawn between human and bovine bacilli, and
      the distinction is best secured by subjecting the organism to a series of tests
      such as I have detailed. The subject is one which ought to be investigated in a
      series of different localities. It is possible that the locus may be a factor in
      the explanation of the difference between the above results and those of other
      observers.

PMID- 19867585
TI  - ACUTE VASCULAR LESIONS IN MICE FOLLOWING INJECTIONS OF PNEUMOCOCCI.
AB  - Mice dying several days after injections of pneumococci, both living and dead,
      frequently show at autopsy large intrathoracic hemorrhages. The histological
      study of the thoracic organs indicates that there occurs in each case a sharply
      circumscribed, acute degeneration of the wall of some large vessel, usually the
      ascending aorta or one of the pulmonary arteries. This degenerated portion is
      torn out by the pressure of the blood with almost complete disappearance of the
      vessel wall, leading to a gross hemorrhage. A similar change is occasionally
      found in the walls of the veins which contain cardiac instead of smooth muscle.
      We have found this lesion only in mice which had been recently inoculated with
      pneumococci. Negative cultures at autopsy, the lack of inflammatory reaction, and
      the occurrence of the conditions after injection of dead pneumococci suggest the
      cause to be a toxic degeneration of the vessel wall brought about by the poisons
      of the injected organisms.

PMID- 19867586
TI  - SINUS STIMULATION AS A FACTOR IN THE RESUSCITATION OF THE HEART.
AB  - The four series of experiments described above indicate clearly that tetanic
      stimulation of the sinus region of the auricles is of material assistance to
      massage in the resuscitation of the heart. It causes the auricles to generate
      impulses, either rhythmical or irregular, to which the ventricles, when
      susceptible, respond. When massage administered for brief periods has failed to
      resuscitate the heart, the same period of massage combined with tetanic
      stimulation of the sinus has usually brought the circulation back to normal. In
      some instances massage alone when continued over long periods has been without
      effect, and to all appearances would have continued to be without effect, whereas
      at such a time massage combined with stimulation of the sinus has effected
      recovery. Whether the stimulus causes the auricles to beat normally or to
      fibrillate seems to make no essential difference in the end result. Not
      infrequently conductivity and irritability are lowered to such an extent by the
      cessation of the circulation, that impulses generated in an auricle started by
      stimulation can at first manifest no effect upon the ventricles. Under such
      circumstances massage alone or, more frequently, massage plus stimulation may
      cause the ventricles to beat with their inherent slow rate. Often then the force
      of the ventricular contractions is insufficient for the maintenance of an
      effective circulation. In such cases, however, with the gradual improvement in
      the condition of the heart, the auricular impulses, as a rule, soon begin to
      reach the ventricles, with the result that the latter immediately begin to beat
      more rapidly and effectively. The beneficial results of stimulation of the
      auricles, therefore, manifest themselves relatively late, but none the less
      effectively. It has been found that even after the heart has begun to beat,
      stimulation of the sinus region may still be of some assistance, though in
      another direction. It not infrequently happens that after resuscitation of the
      heart the blood pressure fails to rise above a certain low and insufficient
      level. In such cases repeated tetanic stimulation of the sinus may accelerate the
      rise of blood pressure and so hasten recovery (protocol of experiment 12, series
      II, and text-figure 5). No attempt has been made to determine the mechanism of
      this effect.

PMID- 19867587
TI  - THE ANTIGENIC PROPERTIES OF SPLIT PRODUCTS OF CASEIN.
AB  - We draw the following conclusions from our experiments on the antigenic
      properties of chemically pure casein and some of its split products. Casein and
      paranuclein have distinct antigenic properties, particularly as shown by their
      ability to sensitize guinea pigs for subsequent anaphylactic intoxication by each
      other or by milk. This sensitizing ability and a corresponding ability to
      intoxicate are indistinguishably equivalent, under the conditions employed. On
      immunizing rabbits by repeated injections of paranuclein or of casein, and
      subsequently testing their sera for precipitins and fixation antibodies, it was
      found that casein apparently produces them much more readily, giving an antiserum
      that reacted (fixation) in very high dilution with casein (0.000,000,1 of a 1 per
      cent. solution), but much less strongly with paranuclein. Only one of two
      antiparanuclein sera showed the presence of antibodies to paranuclein by the
      delicate fixation reaction, and that in relatively small amounts. The two
      antibodies to casein and to paranuclein are, in the case of casein
      quantitatively, and in the case of paranuclein absolutely specific. A solution of
      the products of complete peptic digestion of casein fails to sensitize to
      paranuclein and gives no fixation reaction with an anticasein or antiparanuclein
      serum. It intoxicates animals sensitized to paranuclein but no more markedly than
      it does normal animals. It also fails to show specific intoxication in an animal
      that has been sensitized by the same substance. The amino acids, glutamic acid,
      and leucin, the principal components of their kind in casein, and in the same
      proportion therein present, likewise failed to show antigenic properties. They do
      not sensitize animals to milk intoxication or to intoxication by themselves, and
      likewise failed to produce precipitins in rabbits in a preliminary experiment.
      These experiments are regarded as a fairly systematic analysis of the antigenic
      properties of split products of a single protein. They are analogous to, though
      less complete than the work of Wells (6) on egg-white. They seem to present the
      additional advantage of dealing with what is probably the only protein certainly
      known chemically, and in its purest form. They serve, moreover, as an
      introduction to the following study of the antigenic properties of a combined
      protein.

PMID- 19867588
TI  - THE ANTIGENIC PROPERTIES OF A PROTEIN COMPOUNDED WITH CASEIN.

PMID- 19867589
TI  - STUDIES ON FERMENT ACTION : III. A SPECIFIC IMMUNE LIPASE.
AB  - 1. Erythrocytes have definite lipoidal constituents and lipoidal combinations
      peculiar to the species. 2. Certain lipoids and lipoidal combinations act as
      specific antigens. 3. The increase in serum lipase which occurs upon immunization
      of animals to foreign red cells is, at least in part, specific. 4. This specific
      lipase plays, no doubt, an important part in specific serum hemolyses.

PMID- 19867590
TI  - CONDITIONS GOVERNING THE GROWTH OF DISPLACED NORMAL TISSUE.
AB  - We are unwilling to draw any very definite conclusions from the experiments,
      partly because they show a survival of implanted skin of so much shorter duration
      than that which seems to occur in the case of spontaneous implantation cysts, and
      partly because the method of reexposing the submerged grafts is rather a crude
      way of testing their vitality. Nevertheless, the following points seem clear: 1.
      The repeated transplantation of a piece of skin from one animal to another
      confers no exceptional power of growth upon that skin. 2. The repeated
      implantation of skin into one animal decreases, if anything, its receptivity for
      such grafts. 3. The burial of skin in the interior of the body causes, after a
      time, a change in the skin of such a nature that it cannot resume its normal
      function as an external covering tissue, even when its circulation ? is well
      maintained and it is buried in the body of the same animal. The experiments do
      not determine how long the cells of the skin actually remain alive, and indeed it
      is conceivable that the mere maceration of the protective horny layer puts the
      skin, when reexposed, into the position of a moist tissue, such as the intestinal
      mucosa, so that it readily dries up and succumbs. Nor do the experiments throw
      any light upon the possible existence of cytolytic substances in the circulating
      fluids, although, naturally, the idea of such an action has always been present
      in our minds in observing the gradual loss of vitality in the transplanted
      tissues.

PMID- 19867591
TI  - TESTING FOR EPINEPHRIN (ADRENALIN) IN BLOOD. COMPARISON OF PLASMA AND SERUM.

PMID- 19867592
TI  - LIPOID METABOLISM IN THE DEVELOPING CHICK AND ITS RELATION TO CALCIFICATION.
AB  - The liver of the embryo chick during the first two weeks of development contains
      an abundance of isotropic fatty globules which represent a mixture of lipoids in
      which phosphorized fats predominate. During the third week of incubation the
      fatty globules in the liver change their physical and chemical characters. They
      become anisotropic and exhibit the reactions and properties of esters of
      cholesterol. The phosphorized fats gradually disappear from the liver during the
      third week. The phosphoric acid utilized by the embryo chick in calcification is
      derived from phosphorized fats. It is suggested that the phosphorized fats are
      split in the liver, the glycerophosphoric acid portion being liberated for
      calcification, while the free fatty acids are esterfied by cholesterol. A review
      of chemical analyses of aortic atherosclerosis and calcification made by others,
      and a comparison of the conditions in atherosclerosis with those of the
      developing chick liver, suggest that pathological calcification results from a
      splitting in situ of phosphorized fats with subsequent formation of calcium
      salts, as suggested by Baldauf.

PMID- 19867593
TI  - CELL PROLIFERATION AND PARASITES IN RATS.

PMID- 19867594
TI  - OBSERVATIONS WITH REGARD TO THE ACTION OF EPINEPHRIN ON THE CORONARY ARTERY.
AB  - 1. Excised rings of the coronary artery of the ox properly weighted react to
      epinephrin by dilatation. 2. This reaction of the ox coronary is not an active
      dilatation, but is in the nature of a sudden lowering from a high to a relatively
      low degree of tonus. The tonus is not, however, entirely abolished by epinephrin.
      3. The degree of relaxation produced by epinephrin is not constant. It depends on
      several factors other than the concentration of epinephrin used. 4. It is
      possible to increase the sensitiveness of the coronary artery to epinephrin. 5.
      There is no evidence of any primary constrictor effect on the ox coronary from
      epinephrin in most dilute solutions, nor can the existence in this artery of any
      constrictor mechanism of sympathetic origin be determined by the excised ring
      method.

PMID- 19867595
TI  - THE QUESTION OF EPINEPHRIN IN THE CIRCULATION AND ITS RELATION TO BLOOD PRESSURE.
AB  - 1. The modified Meyer method here proposed, of parallel tests upon segments of
      surviving carotid and coronary arteries from the ox, is a satisfactory means for
      detecting epinephrin in complex body fluids like blood. 2. At the present time
      there is no evidence that epinephrin, in amounts sufficient to produce its
      physiological effects upon any hitherto used test objects, exists in the
      circulating blood, with the exception of blood from the suprarenal vein. 3. The
      examination of uncoagulated blood from six persons with high blood pressure has
      failed to show the presence of epinephrin or other constricting substances. 4.
      The constrictor substance in defibrinated blood and serum is not an epinephrin
      like substance. In its point of action and its effects it is similar to barium
      chlorid. It is a direct stimulant to smooth muscle and seems to have no relation
      to the sympathetic innervation of muscle.

PMID- 19867596
TI  - THE PHYSIOLOGICAL ACTION OF EPINEPHRIN ON THE BRONCHI.

PMID- 19867597
TI  - THE CULTIVATION OF MALARIAL PLASMODIA (PLASMODIUM VIVAX AND PLASMODIUM
      FALCIPARUM) IN VITRO.
AB  - The asexual cycle of Plasmodium vivax and Plasmodium falciparum has been
      cultivated in vitro in human blood. The parasites have been grown also in red
      blood cells in the presence of Locke's solution, free of calcium chlorid and in
      the presence of ascitic fluid. The parasites grow within red blood cells and
      there is no evidence that they can be grown outside of these cells. The parasites
      are destroyed in a very few minutes in vitro by normal human serum or by all
      modifications of serum that we have tested. This fact, together with numerous
      observations of parasites in all stages of growth apparently within red cells,
      renders untenable the idea of extracorpuscular development. Leucocytes
      phagocytize and destroy malarial plasmodia growing in vitro only when the
      parasites escape from their red blood cell capsule or when the latter is
      perforated or becomes permeable. Successive generations of Plasmodium vivax and
      Plasmodium falciparum have been cultivated in vitro by removing the leucocytes
      from the culture and by transplanting to fresh red blood cells and serum at
      proper intervals. The asexual cycle of Plasmodium vivax and Plasmodium falciparum
      cultivated in vitro does not differ from the same cycle growing in vivo. The
      sexual cycle has not been cultivated, though we have obtained some evidence of
      the possibility of its accomplishment. There can no longer be any doubt that
      Plasmodium vivax and Plasmodium falciparum are separate and distinct species.
      When grown in an identical culture medium and under exactly the same conditions
      they remain distinct. In twenty-nine cultures of aestivo-autumnal parasites many
      forms and sizes have been observed, so that evidence is supplied of the
      occurrence of different varieties of aetivo-autumnal malarial plasmodia. The so
      called tertian aetivo-autumnal variety may be seen at the proper stage in all
      cultures grown from merozoites. The form and appearance of the same culture of
      plasmodia may vary greatly under different conditions which are not necessarily
      destructive to the parasites. Their generation period may vary from thirty hours
      (aetivo-autumnal) to four days (tertian), as a result of variation in the
      temperature at which they were cultivated. Sexual parasites grow in the cultures
      and are more resistant to unfavorable conditions than schizonts, often living
      several days after the latter die out. Forms suggesting parthenogenesis have been
      observed.

PMID- 19867598
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON LOCALIZED INFECTIONS : FOURTH PAPER: EXPERIMENTAL
      PNEUMOCOCCIC MENINGITIS AND ITS SPECIFIC TREATMENT.
AB  - Virulent pneumococci injected into the cranial or spinal cavities of monkeys
      produce constantly a meningitis closely resembling pneumococcus meningitis in
      man, except that the experimental disease pursues a more rapid course to the
      invariable death of the untreated animal. An homologous immune pneumococcus serum
      injected into the spinal canal exerts a restraining influence upon the disease to
      the extent that when employed early it prevented, exceptionally, the occurrence
      of infection and thus saved the life of the animal, and when given later it at
      first retarded the disease but subsequently exerted no beneficial action and was
      powerless to save life. A mixture of sodium oleate, immune serum, and boric acid
      exerted regularly a more powerful action than immune serum alone, and not only
      prevented the occurrence of infection but also, when administered repeatedly,
      arrested the progress of an actually established infection and led, often, to the
      enduring and perfect recovery of the inoculated animal. It is proposed to employ
      a similar mixture in the direct treatment of pneumococcic meningitis and possibly
      of still other accessible local pneumococcic infections in man.

PMID- 19867599
TI  - PIGMENT FORMATION IN THE LIVER DURING AUTOLYSIS AND ITS RELATION TO THE
      PIGMENTATION OF HEMOCHROMATOSIS.
AB  - Without claiming any close analogy between the autolytic changes and pigmentation
      in pathological processes, it has, we believe, been shown that iron-containing,
      as well as other kinds of pigments, may be formed during the autolytic
      degeneration of parenchymatous cells independently of the hemoglobin in the blood
      stream, and hence may be derived from the proteid constituents of the cell
      itself.

PMID- 19867600
TI  - NERVE FIBRILS IN THE SINO-AURICULAR NODE.
AB  - Aside from the nerve fibers which enter the pace-making node from the
      subepicardium, there were observed within the limits of the node a few ganglionic
      cells and a plexus of moniliform nerve fibrils in very close relation to its
      muscle fibers, hence the sino-auricular node, like the auriculo-ventricular, may
      be considered from a histological standpoint a neuromuscular organ.

PMID- 19867601
TI  - CULTIVATION OF SPIROCHAETA GALLINARUM.
AB  - 1. Spirochoeta gallinarum can be cultivated in suitable artificial media for many
      successive generations and probably for indefinite periods. The presence of fresh
      tissue and a certain amount of oxygen seems to be essential for its growth. No
      perceptible odor is produced in the cultures. 2. The maximum growth of
      Spirochoeta gallinarum is reached on about the fifth day, but the phase of
      degeneration commences slowly and gradually, so that in this respect the
      gallinarum differs from the duttoni, kochi, obermeieri, or novyi, whose cultures
      are characterized by sudden onset of degeneration soon after the maximum growth
      is attained. 3. No rod formation resembling bacilli arises in the course of
      multiplication of Spirochoeta gallinarum in cultures. Many round or oval bodies
      appear in old cultures, but no infection of animals or formation of spiral forms
      from these granules has been produced. The granules are probably the degeneration
      products derived from the periblast of the spirochoetoe. 4. Cultures of
      Spirochoeta gallinarum, either old or young, do not contain a form which passes
      through a Berkefeld filter (V) that infects chickens or grows into spirochaetae.
      5. Spirochoeta gallinarum remains virulent for chickens after being in cultures
      for at least thirteen generations, but it may become avirulent under certain
      cultural conditions. The inoculation of chickens with the attenuated culture
      renders the birds refractory to the subsequent infection with a virulent strain.
      6. When the spirochaetae are cultivated in the media containing rabbit kidney
      instead of chicken muscle, the individual specimens are somewhat thicker, but
      otherwise typical. 7. Spirochoeta gallinarum multiplies in culture by transverse
      division. No positive evidence of a longitudinal division has been obtained.

PMID- 19867602
TI  - THE DURATION AND EXTENT OF INDUCED RESISTANCE TOWARD TUMOR TRANSPLANTATION IN
      MICE.
AB  - The foregoing experiments demonstrate that the immunity induced in mice by
      preliminary treatment with tumor or certain of the normal tissues reaches its
      maximum at about the tenth day, after which it gradually diminishes, probably to
      disappear after the lapse of about eighty days. It is significant that the curves
      with the three tissues, spontaneous tumor, kidney, and embryo skin, should
      parallel each other so closely, and the occurrence renders extremely probable the
      view, previously expressed by Russell and by Woglom after an examination of very
      young grafts in immune mice and rats respectively, that the resistance elicited
      in each case is similar. It is evident, however, that there is a difference in
      the degree to which it is developed.

PMID- 19867603
TI  - TOXIC SUBSTANCES PRODUCED BY PNEUMOCOCCUS.
AB  - 1. The filtered blood serum of rabbits infected with pneumococci is not toxic. 2.
      Extracts of pneumococci prepared by keeping emulsions of the bacteria in salt
      solution at 37 degrees C. for varying periods of time may be toxic, and when
      injected intravenously into guinea pigs, may produce a train of symptoms followed
      by acute death resembling that seen in acute anaphylaxis. Such extracts, however,
      are not uniformly toxic and it has been impossible to discover the exact
      conditions under which such extracts become toxic. 3. When the centrifugalized
      peritoneal washings of guinea pigs infected with pneumococci are injected into
      the circulation of normal guinea pigs, these animals very frequently exhibit
      symptoms like those seen in acute anaphylaxis, and a considerable proportion of
      the animals die acutely. 4. When pneumococci are dissolved in dilute solutions of
      bile salts and the solution resulting is injected intravenously into rabbits and
      guinea pigs, these animals show with great constancy the same symptoms that are
      seen in acute anaphylaxis. The solution of pneumococci in bile may occur in ten
      minutes at 37 degrees C. or in half an hour on ice. This is considered evidence
      that the toxicity of the solution does not result from digestion of the bacterial
      protein, but is due to substances preformed in the bacterial cells and set free
      on their solution. The toxicity of the solution is diminished or destroyed by
      heating to 55 degrees C. or over.

PMID- 19867604
TI  - THE PRESENCE OF PROTECTIVE SUBSTANCES IN HUMAN SERUM DURING LOBAR PNEUMONIA.
AB  - These experiments demonstrate that protective substances are usually present in
      the blood of patients recovering from lobar pneumonia. As a rule, the appearance
      of protective bodies in the blood, when demonstrable, coincides rather sharply
      with the period of critical fall in temperature and the disappearance of
      symptoms. These substances are not present in the blood in any measurable degree
      before the crisis, but afterward they may reach a considerable concentration. In
      certain instances, protective substances either become evident some time after
      the occurrence of the crisis, or cannot be demonstrated at any period of the
      disease. Experiments in which it is possible to test serum against an homologous
      strain of pneumococcus yield in the majority of cases evidence of the presence of
      protective bodies; whereas in those in which stock cultures are used, the serum,
      as a rule, shows no protection. The development of specific protective substances
      in the serum of patients with lobar pneumonia suggests that these bodies may play
      a part in the mechanism of recovery.

PMID- 19867605
TI  - THE OCCURRENCE AND VIRULENCE OF PNEUMOCOCCI IN THE CIRCULATING BLOOD DURING LOBAR
      PNEUMONIA AND THE SUSCEPTIBILITY OF PNEUMOCOCCUS STRAINS TO UNIVALENT
      ANTIPNEUMOCOCCUS SERUM.
AB  - Studies of the bacteriology of the blood were made in thirty-seven cases of lobar
      pneumonia. The pneumococcus was isolated from the blood in approximately 50 per
      cent. of the cases studied. The course of infection in individuals with
      pneumococcus in the blood was more severe than in those in which no organism
      could be cultivated from the blood. 77 per cent. of the patients with positive
      blood cultures died, and 79 per cent. of patients with negative blood cultures
      recovered. In fatal instances of pneumonia, where the pneumococcus was found in
      the blood, the number of organisms per cubic centimeter of blood was very high in
      the last stage of the disease. In individuals dying of pneumonia without blood
      infection, the disease was characterized by a rapid spread of the local process
      in the lungs. It is not unlikely that the symptoms of collapse, developing on the
      fifth or sixth day of lobar pneumonia, are often the expression of serious
      invasion of the blood by the pneumococcus. In other instances, they mark an
      extension of the local process in the lungs. Strains of pneumococcus isolated
      from the blood of patients with lobar pneumonia were usually of high animal
      virulence. In a few instances where the organism isolated from the blood was of
      low virulence for animals, the patients recovered. The protective power of a
      univalent antipneumococcus serum was tested against nineteen strains of typical
      pneumococcus and against four strains of closely allied organisms. The serum
      manifested some degree of protection against twelve out of nineteen strains of
      typical pneumococci. No protection was observed against the atypical organisms.
      In eight instances the degree of protection obtained was high, in three low, and
      in one there occurred only a prolongation of the period of life of the inoculated
      animal.

PMID- 19867606
TI  - COAGULATION TIME OF THE BLOOD IN LOBAR PNEUMONIA.
AB  - The coagulation time of the blood is generally prolonged during the acute stage
      of lobar pneumonia, returning to normal during the period of convalescence. There
      seems to be a simultaneous increase in the quantity of circulating fibrinogen.
      The lengthening of the coagulation time is probably due to an increased formation
      of antithrombin. The source of the increased antithrombin and fibrinogen is
      probably the liver, and the stimulus to increased production of these two
      substances is due to the nature of the infecting organism.

PMID- 19867607
TI  - THE CARBON DIOXIDE CONTENT OF THE BLOOD IN PNEUMONIA.
AB  - A diminution in the carbon dioxide content of the blood is a constant feature in
      pneumonia. Occasional cases, however, may fail to show low carbon dioxide. The
      carbon dioxide in the blood bears little definite relation to the severity of the
      disease, except that it tends to be lowest in severe cases and in the terminal
      stages of the disease. There is less deviation from the normal in short or mild
      cases. The diminution in the carbon dioxide in the blood bears no immediate
      relation to temperature, as it may persist for some days after the patient is
      afebrile. The diminution in carbon dioxide corresponds to the other evidences of
      metabolic changes in infection and, like them, may be even greater after than
      during the febrile period. The changes in the carbon dioxide content of the blood
      run parallel to the output of ammonia in the urine. The carbon dioxide appears to
      bear no relation to chlorine excretion. In two unusual cases the carbon dioxide
      content of the blood was normal or above normal. This was associated with a very
      low oxygen content of the venous blood.

PMID- 19867608
TI  - A CONTRIBUTION TO THE STUDY OF THE CHEMISTRY OF BLOOD SERUM.
AB  - The most striking feature observed in this study is the extensive variation of
      the serum in relation to its proteins. It was found that in certain diseases the
      globulin fraction is markedly increased, whereas the total protein of the serum
      may be normal, or may fall far below normal in amount. The diseases in which an
      increase in the globulins takes place may be grouped as follows: (1) cardiac
      diseases associated with decompensation and serous effusions, (2) pulmonary or
      respiratory affections of inflammatory or non-inflammatory origin (pneumonia,
      emphysema, polycythemia), (3) diabetes mellitus, and (4) parenchymatous
      nephritis. In the serum of chronic parenchymatous nephritis the increase in the
      globulin content is most pronounced and may constitute nearly all the protein, or
      as much as 95 per cent. The globulin content of serum is normal or diminished in
      the following diseases: (1) simple achylia gastrica (short duration), (2)
      tuberculosis, (3) diabetes insipidus, and (4) chronic interstitial nephritis.
      Other ingredients of the sera analyzed showed variations which cannot be
      definitely classified; but in a general way it appears upon careful analysis that
      an accumulation of water and salt occurs in those diseases in which the globulin
      fraction of the blood serum is increased.

PMID- 19867609
TI  - ON THE DIFFERENCES IN THE EFFECTS OF STIMULATION OF THE TWO VAGUS NERVES ON RATE
      AND CONDUCTION OF THE DOG'S HEART.
AB  - IT MAY BE CONCLUDED FROM THE RESULTS OBTAINED IN THESE EXPERIMENTS : 1. That
      stimulation of the right vagus nerve in the dog usually causes arrest of all the
      chambers of the heart. 2. That stimulation of the left vagus nerve exerts a
      moderate negative chronotropic effect on the auricles. 3. That stimulation of the
      left vagus nerve has a profound effect on the conduction of impulses over the
      auriculoventricular system. 4. That the degree of effect exercised on the
      auriculoventricular system by stimulation of the left vagus nerve varies. In some
      dogs conduction is depressed to an extent which causes only a delay in the
      conduction of impulses from auricles to ventricles (P-R time) ; in other dogs the
      conduction is depressed to a degree which results in incomplete heart-block;
      while in still other dogs conduction is so depressed that although the auricles
      continue to contract, no impulses pass from them to the ventricles. 5. That when
      stimulation of either the right or left vagus nerve causes asystole of nomotopic
      ventricular contractions, ectopic ventricular contractions may occur. 6. That the
      time which elapses before ectopic ventricular contractions occur depends upon the
      irritability of the ventricular muscle, and this may vary in different dogs. 7.
      That stimulation of the left vagus nerve may rarely cause sino-auricular block.
      Possibly stimulation of the right nerve may also produce this effect. 8. That
      there is consequently usually a great qualitative difference in the action of the
      two vagus nerves on the heart of the dog.

PMID- 19867610
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : III. THE CHANGES IN THE BLOOD FOLLOWING SPLENECTOMY AND THEIR RELATION
      TO THE PRODUCTION OF HEMOLYTIC JAUNDICE.
AB  - THE RESULTS OF THIS STUDY OF THE CHANGES IN THE BLOOD AFTER SPLENECTOMY AND OF
      THE EFFECT OF THE ADMINISTRATION OF HEMOLYTIC SERUM ALLOW THE FOLLOWING TENTATIVE
      CONCLUSIONS: 1. The failure of a hemolytic serum to cause jaundice is due in some
      way to the anemia which frequently follows splenectomy. Animals, whether
      splenectomized or not, which have a low blood count and low hemoglobin content do
      not readily develop jaundice after administration of a hemolytic serum. On the
      other hand, in animals with a normal blood picture such a serum readily causes,
      during early periods after splenectomy, a well marked jaundice. 2. The difficulty
      of producing hemoglobinemia and jaundice in animals splenectomized one month or
      more, is due, as shown by blood count, the use of hypotonic salt solution test,
      and by the search for the presence of hemoglobin in the serum and urine, to an
      increase in the resistance of the red cells. The results of detailed serologic
      tests upon this point will be presented later. 3. It is possible that spontaneous
      jaundice occurring at long periods after splenectomy is an accompaniment of the
      complete regeneration of the blood. The study of the blood in animals
      splenectomized for long periods, seven to ten months, indicates that spontaneous
      jaundice occurs only when the animal has recovered from the initial period of
      anemia and has a high red cell count and high hemoglobin content. 4. As to the
      mechanism responsible for the anemia following splenectomy and for the increased
      resistance of the red cells, we can at present offer no explanation.

PMID- 19867611
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : IV. A STUDY, BY THE METHODS OF IMMUNOLOGY, OF THE INCREASED RESISTANCE
      OF THE RED BLOOD CORPUSCLES AFTER SPLENECTOMY.
AB  - 1. The erythrocytes of splenectomized dogs show increased resistance to the
      action of hypotonic salt solutions and to specific hemolytic immune serum. The
      degree of resistance appears to increase with the length of time that has elapsed
      after splenectomy. 2. This increased resistance of the erythrocytes is not due to
      an increased antihemolytic power of the animal's serum or to a diminished
      complementary value of the serum, but is a property depending upon the
      erythrocytes themselves. 3. Non-splenectomized animals receiving a single
      injection of specific hemolytic immune serum and developing a temporary anemia
      show likewise on recovery an increased resistance of the corpuscles without the
      presence of antihemolysin in demonstrable amount. 4. As anemia of varying grade
      is a characteristic result of splenectomy, it would appear that the increased
      resistance of the corpuscles is a concomitant of the regeneration of the red
      cells following such anemia and is thus analogous to the increased resistance of
      such cells not infrequently observed in various forms of experimental anemia. 5.
      There is no evidence to indicate that the anemia after splenectomy is due to the
      presence of hemolytic bodies, or that the increased resistance of the cells is
      due to antihemolytic bodies, accumulating in the serum as the result of the
      ablation of the spleen. It is evident therefore that the spleen in some way
      controls or regulates blood destruction (and regeneration ?), and in the hope of
      throwing light on the subject, an investigation of the bone marrow and lymph
      nodes of splenectomized dogs is now under way.

PMID- 19867613
TI  - NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS OF THE CAT.
AB  - It will be seen that uranium nephritis, which involves both tubules and
      glomeruli, the former more markedly than the latter, produces a marked
      accumulation of nitrogen in the blood. Chromate nephritis, which involves almost
      exclusively the tubules, produces only moderate retention of nitrogen.
      Cantharidin nephritis which involves both tubules and glomeruli, the latter more
      severely than does uranium, produces a marked accumulation of nitrogen, beginning
      early and persisting for a considerable period. The experiments were controlled
      by testing the blood of normal cats kept under the same conditions, these animals
      showing only slight variations from day to day. This general statement is in
      accordance with the physiological classification of these nephritides except that
      the retention in uranium occurs at an early stage, where, according to the
      physiological studies of Schlayer and his associates, and of Pearce, Hill, and
      Eisenbrey, the vascular changes have not as yet appeared. It must be noticed that
      in the three types of nephritis that form the subject of this investigation,
      anatomical study shows the glomerulus to be distinctly involved in the two forms
      where accumulation of nitrogen in the blood is most marked, a condition
      indicating that although almost pure tubular involvement produces only moderate
      accumulation, the additional involvement of the glomerulus is extremely important
      in leading to a retention of nitrogenous waste products. The accumulation of non
      protein nitrogen in the blood and tissues is not large when compared with the
      total intake or elimination of nitrogen, and consequently it is practically
      impossible by means of ordinary nitrogen equilibrium experiments to demonstrate
      the fact of the retention, to say nothing of determining the degree of
      accumulation of waste products accompanying nephritis. That both can be
      demonstrated by the method employed in this research is clearly shown by the
      figures recorded ablove.

PMID- 19867612
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : V. CHANGES IN THE ENDOTHELIAL CELLS OF THE LYMPH NODES AND LIVER IN
      SPLENECTOMIZED ANIMALS RECEIVING HEMOLYTIC SERUM.
AB  - In a large proportion of dogs that have been splenectomized for periods of two
      weeks or more, one finds a great increase in the number of endothelial cells of
      the lymph nodes. In most splenectomized dogs that succumb to an injection of
      hemolytic immune serum within forty-eight hours, the sinuses of the lymph nodes
      contain large numbers of endothelial cells, phagocytic for red cells. This is not
      seen in normal dogs receiving hemolytic serum. Likewise a similar power of
      phagocytosis is seen frequently in the stellate cells of the capillaries of the
      liver. Both in the lymph nodes and the liver these cells appear to be formed in
      situ; we find no evidence that they have been transported to these organs. Such
      findings suggest the development of a compensatory function on the part of the
      lymph nodes and possibly of the liver. Normally the spleen contains cells which
      have the power to engulf and presumably to destroy the red blood corpuscles. In
      certain pathological conditions this function is frequently greatly augmented and
      may sometimes be shared by the lymph nodes, for example, in typhoid fever, as was
      first clearly shown by Mallory. Our observations suggest that in the absence of
      the spleen, this function of forming red blood corpuscle-phagocyting cells,
      normally a minor activity of the lymph nodes, becomes highly developed in the
      latter organs, and that these cells, and the stellate cells of the liver, thus
      assume, in part at least, the function of destroying red blood corpuscles by
      phagocytosis. In view of the somewhat limited material at our disposal, we offer
      this, not as definitely conclusive, but as evidence which, in connection with the
      work of others, is highly suggestive of the possibility of the lymph nodes
      assuming some of the function of the spleen. Whether this activity of the
      endothelial cells of the lymph nodes and the liver has any bearing on the anemia
      that follows splenectomy and on the occurrence of spontaneous jaundice in the
      late periods after splenectomy, is not yet clear.

PMID- 19867614
TI  - A CONTRIBUTION TO THE PATHOLOGY OF PRIMARY SPLENOMEGALY (GAUCHER TYPE), WITH THE
      REPORT OF AN AUTOPSY ON A MALE CHILD FOUR AND ONE HALF YEARS OF AGE.
AB  - As a result of this study it may be stated that primary splenomegaly of the
      Gaucher type is a distinct disease, related in all probability to the blood
      diseases. It begins usually at an early age, frequently affects several members
      of a family, and runs a chronic course. The clinical manifestations are:
      pronounced hypertrophy of the spleen, subsequent enlargement of the liver,
      absence of palpable lymph nodes, absence of jaundice and ascites, absence of
      characteristic blood changes, discoloration or pigmentation of the skin, and a
      tendency to epistaxis or other hemorrhages. The lesions are found in the spleen,
      lymph nodes, bone marrow, and liver. These organs show the presence of iron
      containing pigment, and large multinuclear cells with a characteristic cytoplasm.
      In the early cases peculiar large phagocytic cells arising from atypical large
      lymphocytes are found in the follicles (keimcentra) of the hemapoietic system.
      After leaving the follicles these cells possess phagocytic qualities for a
      certain period. As a result of the phagocytosisthe cells enlarge, the nature of
      the cytoplasm changes, and the cells acquire a characteristic vacuolated and
      wrinkled appearance. The cells are carried from the spleen through the portal
      system to the liver, where they are destroyed. The irritation produced by this
      destructive process gives rise to an increase in the intralobular connective
      tissue. The disease is eminently a chronic one, without any of the manifestations
      of malignancy, and always terminating as the result of some intercurrent
      affection. The etiology is unknown, although a family predisposition to some
      toxic agent which causes an irritability of the follicles in the hemapoietic
      system probably exists. The possibility of some protozoan infection as an
      etiological factor must not be overlooked.

PMID- 19867615
TI  - THE SELECTIVE ACTION OF GENTIAN VIOLET ON CLOSELY RELATED BACTERIAL STRAINS.

PMID- 19867616
TI  - LYMPH FORMATION AND EDEMA OF THE LIVER WITH EXPERIMENTAL NEPHRITIS PRODUCED BY
      CANTHARIDIN.

PMID- 19867617
TI  - EXPERIMENTS ON INSECT TRANSMISSION OF THE VIRUS OF POLIOMYELITIS.
AB  - The domestic fly (Musca domestica) can carry the virus of poliomyelitis in an
      active state for several days upon the surface of the body and for several hours
      within the gastro-intestinal tract. Mosquitos (Culex pipiens, Culex sollicitans,
      and Culex cantator), in our experiments, have not taken up and maintained in a
      living state the virus from the spinal cord of monkeys. Lice (Pediculus capitis
      and Pediculus vestimenti) have not taken the virus out of the blood of monkeys or
      maintained it in a living state. The bedbug (Cimex lectularius) has taken the
      virus with the blood from infected monkeys and maintained it in a living state
      within the body for a period of seven days.

PMID- 19867618
TI  - STUDIES ON FERMENT ACTION : V. IMMUNIZATION WITH PROTEOLYTIC CLEAVAGE PRODUCTS OF
      PNEUMOCOCCI.
AB  - 1. Leucoprotease splits pneumococci into lower cleavage products than are
      obtained with the autolytic ferment contained in the pneumococci. 2. Such
      cleavage products injected into rabbits have the property of producing immune
      bodies in the blood of the injected animals. 3. These experiments indicate that
      proteolysis plays a part in the production of pneumococcus immunity.

PMID- 19867619
TI  - THE EFFECTS OF SUBDURAL INJECTIONS OF LEUCOCYTES ON THE DEVELOPMENT AND COURSE OF
      EXPERIMENTAL TUBERCULOUS MENINGITIS.
AB  - Rabbit leucocytes, injected into the basal meninges of dogs, in doses from 0.7 to
      one cubic centimeter apparently invariably cause death. Horse leucocytes,
      injected in the same amounts, cause death in about 25 per cent. of the dogs. .
      The injection of foreign leucocytes into the meninges of monkeys causes few if
      any symptoms. The injection of from one to three cubic centimeters of horse
      leucocytes into the meningeal cavities of dogs, simultaneously with the
      inoculation of the meninges with tubercle bacilli, causes a slight delay in the
      development of the paralytic symptoms in about half the treated animals. This
      delay, however, is very slight when compared with the remarkable prolongation of
      the latent period previously observed after treatment with dog leucocytes. The
      injection of foreign leucocytes into the meningeal cavities of monkeys has thus
      far given almost uniformly negative results. In one small group of monkeys,
      however, inoculated by the method of lumbar puncture, the injection of rabbit
      leucocytes has been associated with a prolongation of the latent period in one of
      the treated monkeys, and with a complete prevention of the subsequent
      tuberculosis in a second monkey.

PMID- 19867620
TI  - ARTIFICIAL ACTIVATION OF THE GROWTH IN VITRO OF CONNECTIVE TISSUE.
AB  - The experiments have shown that extracts of tissues and tissue juices, under
      certain conditions, accelerate the growth in intro of the connective tissue from
      about three to forty times. This activating power was found in many tissues. It
      was much more marked, however, with the extracts of embryos, of adult spleen, and
      of the Rous sarcoma. The power diminished directly with the dilution of the
      extracts, and appeared not to apply to the tissues of a heterologous animal. The
      power was reduced when heated at 56 degrees C., and removed when heated at 70
      degrees C. It was diminished markedly by filtration through a Berkefield filter
      and was completely suppressed by filtration through a Chamberland filter.
      Possibly the finding of the activating power of tissue extracts will have no
      immediate practical application. Nevertheless, it may be indirectly useful by
      leading to the discovery of some of the factors determining the growth of tissues
      and of the unknown laws of cell dynamics, and may ultimately throw light on the
      mechanism of the cicatrization of wounds.

PMID- 19867621
TI  - THE NATURE AND ORIGIN OF THE NITROGENOUS COMPOUNDS IN THE FECES IN INFANTILISM.

PMID- 19867622
TI  - THE CAUSE OF THE EXCESSIVE CALCIUM EXCRETION THROUGH THE FECES IN INFANTILISM.
AB  - Analyses of the principal known bases and acids of the feces in cases of
      infantilism in which excessive amounts of calcium are being lost, and comparison
      with cases which are normal in this respect, show that the fats, fatty acids, and
      volatile acids are not high, and lead to the conclusion that the loss of calcium
      is not secondary to the presence of large quantities of phosphates, fatty acids,
      or volatile acids.

PMID- 19867623
TI  - THE NEGRI BODIES IN RABIES.
AB  - 1. The Negri bodies, as the etiological agent in rabies, present two general
      types or phases in morphology, in growth, and in reproduction. 2. These two
      phases are constantly cyclic in their development and correspond (1) to a
      multiplicative, or schizogonous, and (2) to a reproductive, or sporogonous, life
      cycle. 3. By the detailed study of these forms and their succeeding stages we are
      inclined to believe that the Negri bodies are definite protozoan parasites, and
      from a study of their life history we are led to place them in the suborder of
      Cryptocysts, or Microsporidia, of the Sporozoa, and more definitely among the
      Oligosporogenea of the Glugeidae family, which forms produce but one
      pansporoblast. With the recent advances in the growth of tissues outside the
      body, particularly the work of Carrel, Burrows, Harrison, Lewis and Lewis, and
      Rous upon the infectiousness of tumor extracts, with the results of Noguchi in
      cultivating pathogenic Treponema pallidum, important discoveries concerning the
      Negri bodies will undoubtedly be made in the near future.

PMID- 19867624
TI  - THE GROWTH OF CHICKEN BONE MARROW IN VITRO AND ITS BEARING ON HEMATOGENESIS IN
      ADULT LIFE.
AB  - 1. The development of the polymorphonuclear leucocyte from a mesenchymal,
      lymphoid type of cell is possible in adult life and in vitro in chicken bone
      marrow. 2. These cells can rapidly proliferate by means of amitotic division of
      an unripe form very similar to, but smaller than themselves. 3. All the cells of
      chicken bone marrow can undergo a transformation to a type of cell resembling,
      although not proved to be identical with the cells of connective tissue.

PMID- 19867625
TI  - STUDIES ON FERMENT ACTION : VI. THE RELATION OF IMMUNE SERUM LIPASE TO HEMOLYSIS.
AB  - 1. The specific lipase of immune hemolytic serum is not necessary for hemolysis,
      but this does not prove the non-necessity of a lipolytic action in serum
      hemolysis, since a lipase is always present in the complement serum. 2. Serum
      lipase is found in the end-piece of split complement. 3. There is a parallelism
      between the lipase content and complement strength of the sera of different
      animals (man, rabbit, guinea pig, sheep, ox, cat).

PMID- 19867626
TI  - STUDIES OF THE INORGANIC METABOLISM IN PNEUMONIA WITH ESPECIAL REFERENCE TO
      CALCIUM AND MAGNESIUM.
AB  - During pneumonia the metabolism of inorganic substances deviates markedly from
      the normal. While chlorine, sodium, and calcium are retained in the body,
      potassium and magnesium are excreted normally or in excess. Two cases showed a
      definite loss of magnesium to the body in the febrile period. During the period
      of retention the chlorine content of the blood is distinctly lower than normally,
      the calcium content is apparently slightly lower, and the magnesium content tends
      also to be a little lower. The skin is shown, to play no special part in the
      chlorine retention. Since no organ or organs have been shown to store up large
      amounts of the retained substances, it is probable that they are spread diffusely
      throughout the body.

PMID- 19867627
TI  - ABSORPTION OF ARSENIC FOLLOWING INTRA-MUSCULAR INJECTIONS OF SALVARSAN AND
      NEOSALVARSAN.
AB  - Intramuscular injection of salvarsan and neosalvarsan in rabbits always produces
      necrosis of the muscles. A much more intense reaction is produced by salvarsan
      than by neosalvarsan. The rate of absorption of arsenic following intramuscular
      injections of salvarsan is very slow, while following intramuscular injections of
      neosalvarsan between 75 and 85 per cent of the arsenic is absorbed during the
      first week. The subsequent absorption is quite slow.

PMID- 19867628
TI  - CULTIVATION OF TREPONEMA CALLIGYRUM (NEW SPECIES) FROM CONDYLOMATA OF MAN.
AB  - 1. On the surface of genital or anal lesions, either syphilitic or non
      syphilitic, there may be found occasionally a spirochaeta resembling Treponema
      pallidum, but somewhat thicker than the latter. In general characteristics, this
      organism occupies an intermediary position between Treponema pallidum and
      Spirochaeta refringens. 2. The treponema was obtained in pure culture from two
      cases. For the organism the name of Treponema calligyrum is proposed. 3.
      Treponema calligyrum is non-pathogenic for monkeys and rabbits. 4. Treponema
      calligyrum can be distinguished from Treponema pallidum, Treponema microdentium,
      Treponema macrodentium, Treponema mucosum, and Spirochaeta refringens either by
      the morphology, cultural and biological properties, or all these conditions in
      combination. 5. Under certain cultural conditions Treponema calligyrum becomes
      thinner and may cause some difficulty of differentiation from a strain of the
      thick type of Treponema pallidum, especially when the latter is grown under
      conditions which tend to render it thicker. There is no such difficulty when the
      average and thin types of Treponema pallidum are concerned. On the other hand, by
      providing the calligyrum with conditions which lead to the appearance of thicker
      specimens and by supplying Spirochaeta refringens with conditions of growth that
      favor the development of individuals that are thinner and more regularly curved,
      the refringens may be made to resemble the calligyrum in general appearance; but
      under identical cultural conditions they can be readily distinguished.

PMID- 19867629
TI  - ON THE CLASSIFICATION OF THE STREPTOTHRICES, PARTICULARLY IN THEIR RELATION TO
      BACTERIA.
AB  - It is impossible from any point of view, morphological, biological or
      serological, to draw a sharp dividing line in this series. The forms change
      gradually from the mycelial organism to the bacillary, acid-fast organism. It is
      biologically a group complex and should be so considered. No doubt experiments
      with a larger series of species would yield results giving a possibility of
      closer classification and the introduction of some of the forms now in a
      debatable position, as Bacillus diphtheriae and Bacillus mallei, and other
      organisms, sometimes called, on account of their morphological irregularities,
      corynebacterium and mycobacterium, would help to show their real relation to both
      the Streptothrices and the true bacteria. The latter in many ways are
      acknowledged to be far from primitive; their endospores, flagella, and food
      habits all indicate a relatively high degree of specialization. Hence it would
      seem biologically more reasonable to look upon this group of Streptothrices with
      their variable morphology and close relationships as representing the ancestral
      type that gave rise to both the higher fungi and true bacteria, and not as being
      themselves higher bacteria. The various bacteria, other than the acid-fast forms,
      can readily have arisen from the non-acid-fast bacillary types, or even as non
      acid-fast specializations of the mixed types. All the various forms shown at
      present by the bacteria,-cocci, spirilla, bacilli, etc.,-either separate or in
      chains and masses, are to be recognized in this group, and specializations in one
      or another line in the past would readily have given rise to the types we
      consider true bacteria. The processes of evolution have carried them far away
      from the parent stock and made them into this group. The recognition of this
      group complex and of the intermediate forms indicates clearly the past history
      and present relations of these interesting organisms. These relations may be
      represented by the following scheme. See PDF for Structure It is probable that
      the relation between the acid-fast organisms and the Streptothrices is a closer
      one than that between the Streptothrices and the bacteria, perhaps close enough
      to warrant a common genus for both.

PMID- 19867630
TI  - ON ANAPHYLATOXINS AND ENDOTOXINS OF THE TYPHOID BACILLUS.
AB  - The experiments recorded in this paper confirm the observations of Friedberger
      that acutely toxic bodies can be produced from typhoid bacilli by the action of
      sensitizer and complement and that, when small quantities of bacteria are used,
      an excess of sensitization either interferes with the formation of the poisons or
      leads to a cleavage of the bacterial proteid beyond the poisonous intermediate
      products spoken of as anaphylatoxins. Unlike the experience of other workers with
      poisons of this nature, however, our experiments have shown that the action of
      complement upon typhoid bacilli strongly sensitized or not at all sensitized may
      be carried on, at body temperature, for considerably longer than twelve hours
      without leading to a destruction of the poisons, and that this is true when the
      quantities of the bacteria used vary within the wide range of from one to twelve
      agar slants. It has been found, in fact, that in the case of this microorganism
      prolonged exposure at the higher temperature of considerable quantities of
      bacteria constitutes an unfailing method of regularly obtaining powerful poisons.
      The results obtained by the use of smaller quantities and the less vigorous
      complement action at low temperatures are far less regular or satisfactory. It
      would appear from this that complement action of considerable vigor is required
      to obtain from this bacillus any appreciable yield of anaphylatoxin, and that the
      poison, once formed, is not as unstable as that found in other microorganisms by
      Neufeld and Dold and others. In fact, although we have never observed complete
      lysis in vitro of the typhoid bacilli treated with antibody and complement, the
      sensitized bacteria exposed to the action of complement for as long as fifteen
      hours at 37.5 degrees C. showed, in our experiments, much disintegration, and yet
      powerful poisons were present. Were the influence of lysis or of the too vigorous
      action of the serum bodies as rapidly poison-destroying in the case of this
      bacillus as it has been shown to be in the case of some other bacteria, it would
      be hard to understand how anaphylatoxins could play any part in the toxemia of
      typhoid fever. This phase of our experiments, however, seems to indicate that the
      conditions prevailing in the infected body at the height of this disease would
      furnish ideal criteria for anaphylatoxin production, since, in such cases,
      vigorously sensitized bacilli, in large numbers, are under the prolonged
      influence of considerable quantities of complement, conditions exactly comparable
      to those prevailing in our experiments. Granted that this state of affairs is
      actually the case, then the subsidence of the disease might depend merely upon
      limitation of the supply of antigen, as the increasing bactericidal action of the
      blood constituents come into play, and upon the consequent diminution of the
      anaphylatoxin. For as the bacteria diminish and the sensitizer increases, a
      changed proportion between them is established which, finally, as experiment has
      shown, results in a failure of anaphylatoxin production. For although our
      experiments have shown that, within a wide latitude of relative proportions of
      bacteria and antibody, anaphylatoxin can be formed, beyond this range an excess
      of one or the other element eventually will prevent their formation. It is not,
      however, the purpose of this paper to discuss the mechanism of the subsidence of
      the disease since this phase of the work will necessitate further experimental
      study. In regard to the experiments with kaolin, we were unable to confirm the
      contention of Keysser and Wassermann, though it is more than likely that toxic
      bodies could be formed by the action of complement upon any foreign proteid
      rendered amenable to its action. We are not inclined to attribute too much
      importance to these negative results, recording them merely as they occurred.
      However, should it be found subsequently that anaphylatoxins can be formed in
      this way, it seems unlikely that they are formed from the sensitizer or
      amboceptor as matrix, since this was not specifically adsorbed out of
      concentrated serum by the kaolin in our experiments. On the basis of experiments
      with so called endotoxins, ,we feel that the existence of such preformed
      intracellular poisons as an element in typhoid toxemia has not been proved, and
      is not absolutely necessary for the explanation of the phenomena occurring in
      this disease. However, the diarrhea, the hemorrhagic lesions, and the protracted
      symptoms following the injection of extracts and filtrates of the bacillus,
      differing so strikingly from the acute illness with rapid death or equally rapid
      recovery resulting from anaphylatoxin poisoning, would justify the assumption
      that poisons of this nature may still play a part in the disease, adding an
      additional specific characteristic to the clinical picture. As stated before,
      however, it is not improbable that all these characteristics may represent merely
      a more protracted or subacute state of anaphylatoxin toxemia. The experiments
      with autolysates, although none of them were fatal in their results upon guinea
      pigs, have sufficiently indicated that poisons comparable to anaphylatoxins can
      be formed in this way. This would indicate that a reaction of proteolysis, which
      may take place slowly by autolysis, is hastened by the action of complement, and
      its velocity is still further augmented by the increase, within certain limits,
      of the sensitization,-a conception which would attribute to the combined action
      of complement and sensitizer a function not incomparable to that of the bodies
      spoken of as catalytic agents.

PMID- 19867631
TI  - ORGANIC MATTER IN THE EXPIRED BREATH WITH ESPECIAL REFERENCE TO ITS INHIBITING
      POWER ON OXIDIZING FERMENTS.
AB  - Weichardt claims to have demonstrated the presence of an organic body in the
      expired air. He allowed the exhaled breath to pass through hydrochloric acid
      solution, evaporated the resulting solution to dryness on a water bath, and
      obtained a weighable residue which charred on ignition. If he neutralized the
      acid solution and concentrated it under reduced pressure, he obtained a solution
      which inhibited the bluing of the guaiacum indicator by blood. By exposing
      calcium chloride in a room in which the air had been vitiated, he claimed also to
      have obtained a substance from the air which prevented the bluing of the guaiacum
      indicator by blood. The experiments here recorded show that a variable amount of
      matter is retained by weak hydrochloric solution when exhaled breath is passed
      through it, and that this matter is volatile on ignition. Contrary to the
      findings of Weichardt, there is no charring or blackening. Nesslerization shows
      the residue to consist mainly, if not wholly, of ammonium chloride. This ammonia
      is believed to have come from the decomposition of food particles about the
      teeth. In one case the person (S.) had smoked just before the experiment, so that
      a small amount of the ammonia from the tobacco smoke may have been held
      temporarily by the saliva and food particles in the mouth and been given off
      gradually during the experiment. Weichardt's experiments on the inhibition of the
      guaiacum test for blood by means of the substances retained when exhaled breath
      is passed through hydrochloric acid or over calcium chloride crystals are not
      corroborated. It is further shown that the guaiacum indicator is unreliable for
      these tests in view of the fact that a small amount of free acid or free alkali
      will inhibit the guaiacum test for blood. This fact is offered as a probable
      explanation of Weichardt's results. Calcium chloride alone gives a deep blue
      color with the guaiacin indicator. Weichardt used this salt to collect from the
      expired breath certain unknown substances which he claims inhibit the oxidation
      of guaiacum by blood. His results are therefore inconclusive. The phenolphthalin
      test for blood has been studied in this connection and further light has been
      thrown on this reaction. The sodium salt of phenolphthalin is colorless in
      alkaline solution, and is readily oxidized by minute quantities of blood to
      phenolphthalein which gives a characteristic deep purplish red color in alkaline
      solution. It has been found that the presence of calcium chloride and ammonium
      chloride in small amounts retards and, in large amounts, prevents this reaction.
      It is believed that any salt composed of a weak base combined with a strong acid
      will have the same effect. This is discussed in the text. It has also been shown
      that the presence of calcium chloride or ammonium chloride decreases the depth of
      color of phenolphthalein in sodium hydroxide solution. Carbon dioxide also
      prevents the oxidation of phenolphthalin by blood. Of course this does not mean
      that carbon dioxide prevents the action of the oxidizing ferments generally. In
      this particular case the substance to be oxidized, namely phenolphthalin, was not
      allowed by reason of the presence of the carbon dioxide to combine with the
      alkali and thereby assume a state in which it could be easily oxidized. The
      results of one experiment seem to indicate a relation between the amount of
      dissolved oxygen in the solutions and the percentage of oxidation. Sodium
      chloride either alone or with the aid of hydrogen peroxide is able to bring about
      the oxidation of phenolphthalin in alkali to a very slight extent (3.5 to 5 per
      cent. in twenty-four hours). Therefore phenolphthalin as a test for oxidizing
      ferments should not be used in the presence of an appreciable amount of inorganic
      salts or carbon dioxide. Complete dialysis is recommended in these cases. It is
      also to be noted that the great delicacy of the test allows considerable
      dilution. Liquids were obtained from the expired breath by passing this through
      weak hydrochloric acid or by condensing the moisture in it by conducting it
      through cooled Drechsel bottles. Attempts were then made to prove the presence in
      these liquids of some substance which inhibits the oxidation of phenolphthalin by
      blood, but all were unsuccessful. Moreover attempts to concentrate these liquids
      by evaporation under reduced pressure or by the passage of a direct current
      (colloidal travel) were also unsuccessful. It is planned to improve upon the
      apparatus used to concentrate colloids by the passage of a direct current, and to
      test the effect of expired breath products on the rate of oxidation of
      phenolphthalin by blood.

PMID- 19867632
TI  - A COMPARISON OF THE ACTION OF PLASMA AND SERUM ON CERTAIN OBJECTS USED IN
      BIOLOGICAL TESTS FOR EPINEPHRIN.
AB  - Apparently, then, we are confronted with this result,-that citrate plasma which
      causes little or no constriction of the stretched artery ring, little or no
      slowing of the flow through the frog perfusion preparation, while the
      corresponding serum produces a marked effect on both preparations, will affect
      the intestine or uterus preparation practically in the same way as the
      corresponding serum. Hirudin plasma and serum exert on the intestine and uterus
      preparations practically the same effect, causing a marked increase of tone. On
      the artery ring preparation, there is a difference although it is not so strongly
      marked as in the case of the citrate material. The frog perfusion preparation, as
      regards the effect of the hirudin material, seems to occupy an intermediate
      position between the intestine and uterus on the one hand, and the artery ring on
      the other. Of the three plasmas, the peptone plasma most closely resembles serum
      in its action on the artery rings. Like the other plasmas its effect on the
      intestine and uterus does not differ appreciably from that of the serum. From
      these observations the following conclusions seem justified. A change occurs in
      shed blood which confers on it the property of constricting artery rings and of
      slowing the flow through the perfused frog preparation. If this property is in
      any degree possessed by circulating blood it is at least markedly increased after
      the blood is shed. The change, whatever it may be, does not entail any essential
      alteration in the action of the blood on intestine and uterus segments. The tone
      increasing property developed in the shed blood may, therefore, so far as the
      four test objects included in the present survey are concerned, be looked upon as
      especially affecting the blood vessels and probably their smooth muscle directly.
      This need not imply that the pressor substance, if it is a single definite
      substance developed in the shed blood, exerts no action on the smooth muscle of
      the intestine and uterus preparations, but merely that its action on these
      objects is masked by the general action of the serum and plasma, so that in the
      presence of the other constituents common to serum and plasma, its effect is
      inconspicuous or not to be detected at all, while on the blood vessel
      preparations, especially the artery rings, the effect of the pressor substance is
      the dominant one, and the general action of the serum and plasma is feeble or
      undetectable. It is not the clotting process as such, i.e., the actual change of
      fibrinogen into fibrin, that is responsible for the differences between serum and
      plasma revealed by the biological tests employed but some process which precedes
      or accompanies the clotting and which may or may not be causally related to it.
      Changes in formed elements of the blood under the influence of the changed
      conditions (contact with foreign bodies, restriction of gaseous exchange, etc.).
      which blood encounters as soon as it leaves the living vessels, are known to
      occur. Among these it is to be assumed are the changes which condition the
      differences between plasma and serum under discussion.(16) Even if these changes
      represent preliminary stages in coagulation (liberation of the factors necessary
      to the formation of thrombin, for instance), they may still occur to a greater or
      less extent in blood which is prevented in certain ways from clotting since it is
      known that the procedures by which the various non-coagulable plasmas are
      obtained break at different points the chain of events which normally ends in
      coagulation. A procedure which simply supplies sufficient antithrombin to
      neutralize the thrombin which has been allowed to form in normal amount may not
      interfere at all with the changes in the formed elements, and the pressor
      property of the resulting plasma may then be as marked as that of the serum. On
      the other hand, a procedure which binders clotting by preventing or diminishing
      the alterations in the cells, for example, the addition of a substance which acts
      as a preservative for blood platelets, will very likely yield a plasma with
      little or no pressor effect in comparison with the serum. The mere prevention of
      clotting, then, except in so far as it is an index of the prevention of changes
      in the formed elements may have little significance in preventing the development
      of the pressor property. Indeed it is conceivable that the alterations in the
      cells which are connected with the development of this property may even be
      wholly or partially independent of the cell changes concerned in coagulation. In
      this case it might be possible to obtain blood which would clot without
      developing the pressor property. The main results which seem to follow from our
      observations may be thus summarized: 1. The substance, or property, developed in
      shed blood by which it causes constriction of artery rings, is not developed, or
      at least not mainly developed, in connection with the actual change of fibrinogen
      to fibrin, since the constrictor action of different plasmas differs greatly,
      while the absence of coagulation is common to all. 2. The development of the
      constrictor substance, or property, is associated with changes undergone probably
      by formed elements of the blood when it is shed. These changes may be identical
      with the alterations, or with some of the alterations, preliminary to clotting.
      It is possible, however, that there may be changes connected with the development
      of the pressor property which, although concomitant with the liberation of the
      substances concerned in the production of thrombin, are yet quite independent of
      the clotting process. Our observations do not enable us to decide definitely
      between these possibilities. 3. The constrictor substance, or property, developed
      in shed blood acts especially on blood vessels and does not equally affect the
      other organs examined. This follows from the fact that a plasma and serum which
      differ markedly in their action on the blood vessels may have practically the
      same action on the intestine or uterus segments, an action which must therefore
      reside mainly, at least, in the original plasma itself. 4. The indication that
      the serum acts especially on blood vessels increases the interest of the
      suggestion that this action may play an important part in the prompt sealing of
      wounded vessels in addition to the mechanical effect of the clot, or by coming
      into operation before the clot has fully formed.

PMID- 19867633
TI  - THE ACTION OF HYDROCELE FLUID AND CERTAIN OTHER PATHOLOGICAL LIQUIDS ON SOME OF
      THE OBJECTS USED IN BIOLOGICAL TESTS FOR EPINEPHRIN.

PMID- 19867634
TI  - STUDIES OF THE DEGENERATION AND REGENERATION OF AXIS CYLINDERS IN VITRO.
AB  - 1. The brains of chick embryos, of cats six weeks old, of rabbits two months old,
      and of dogs three weeks old, when cultivated in vitro, develop long filaments
      which, according to their growth and their anatomical and tinctorial characters,
      must be considered as true axis cylinders. 2. Similar structures develop from
      spinal ganglia of rabbits seven months old, and from the spinal cord of cats six
      weeks old, and of rabbits two months old. 3. When severed from their origin by
      section these threads undergo degenerative changes which do not appear after nine
      hours, but which are seen after twenty hours, and continue until in the course of
      the following two days the thread degenerates completely. 4. After twenty hours
      the development of new axis cylinders from the central part of the cut fibers is
      observed.

PMID- 19867635
TI  - INTESTINAL OBSTRUCTION IN THE RABBIT. I.

PMID- 19867636
TI  - INTESTINAL ABSORPTION IN INFANTILISM.

PMID- 19867637
TI  - THE CAUSE OF THE FAILURE TO DEVELOP IN INFANTILISM.

PMID- 19867638
TI  - THE ROLE OF THE LIPOIDS AND PARTICULARLY LECITHIN IN NARCOSIS.

PMID- 19867639
TI  - VARIATIONS IN A CHICKEN SARCOMA CAUSED BY A FILTERABLE AGENT.
AB  - Variations are described which have from time to time occurred in the structure
      and behavior of a transplantable, spindle-celled sarcoma of the fowl, a growth
      caused, as elsewhere shown, by a filterable agent. Of late the growth has
      frequently given rise to fatal hemorrhages from its substance. In some of the
      recent, rapidly growing tumors the cells have tended to be spherical, showing
      only a very tardy and imperfect differentiation to the spindle form. A giant
      celled form of the growth is sometimes met with. Despite their diversity the
      tumors grade into one another and in the final analysis are all to be considered
      as spindle-celled sarcomata. Attempts to obtain an action of the etiological
      agent upon cells other than those it usually affects have failed, as have
      attempts to bring about changes in the histology of the sarcomata by attenuating
      the agent. Some of the lesser morphological variations in the sarcoma are
      undoubtedly due to local conditions in the host, and of the more important
      changes some have been associated with an increase in the growth's malignancy.
      For others the determining conditions have yet to be discovered. On the whole the
      variations described are not more marked than those occasionally manifested by
      the transplantable mammalian tumors, and traceable to the changes in a single
      strain of tumor cells during their propagation in successive hosts. In mammals
      the ultimate reason for these changes is not known. In the case of the chicken
      tumor some of them are undoubtedly the expression of changes in the growth's
      causative agent.

PMID- 19867640
TI  - A DEMONSTRATION OF TREPONEMA PALLIDUM IN THE BRAIN IN CASES OF GENERAL PARALYSIS.

PMID- 19867641
TI  - A STUDY OF CULTURES FROM SPUTUM AND BLOOD IN LOBAR PNEUMONIA.
AB  - In the thirty-two unselected cases studied, cultures were taken from both the
      blood and the sputum, and in five of these more than one blood culture was taken.
      In one case the culture was taken from the blood only, and in this instance the
      pneumococcus was found. This case will be considered only with reference to the
      incidence of the pneumococci in blood cultures in lobar pneumonia. The results in
      the thirty-two cases in which cultures were made both from the blood and the
      sputum are as follows: 1. In eleven cases the blood and sputum cultures were
      positive. (a) In nine cases the pneumococcus was isolated, and five of these
      patients died. (b) In two cases, instead of the pneumococcus, Streptococcus
      hemolysans (longus) was found. One of these patients died. 2. In twenty-one cases
      the blood cultures were negative, and in eighteen of these the sputum cultures
      were positive and in three negative. In these three the only result recorded was
      the absence of the pneumococcus. (a) In nine cases the pneumococcus was isolated.
      Two of these patients died. (b) In twelve cases no pneumococcus was found. Two of
      these patients died. Of the patients in which no pneumococcus was found, in two
      cases Bacillus coli was isolated; in one case Micrococcus catarrhalis; in one
      case a staphylococcus (type not stated); in two cases staphylococcus and
      streptococcus; in one case Bacillus influenzae, in one case Bacillus fluorescens
      non-liquefaciens; in one case an unidentified Gram positive chromogenic organism,
      probably saprophytic; and in three cases there are no recorded results except
      that the pneumococcus was absent. In the total of thirty-three blood cultures,
      the pneumococcus was found in ten cases (30.3 per cent.), and six of the patients
      died. During the years 1910 to 1912 sputum cultures were taken from forty-four
      cases of pneumonia, of which twenty-four showed pneumococci (54 per cent.), and
      twenty showed no pneumococci (45 per cent.).

PMID- 19867642
TI  - PANCREATIC TRANSPLANTATIONS IN THE SPLEEN.
AB  - Pancreatic tissue implanted in the spleen and separated from its original
      vascular and nervous connections can live and functionate for months. A small
      nodule of pancreatic tissue composed of acini without demonstrable islands of
      Langerhans prevented the development of diabetes. Death occurred 187 days after
      the extirpation of the pancreas.

PMID- 19867643
TI  - THE PERMANENT LIFE OF CONNECTIVE TISSUE OUTSIDE OF THE ORGANISM.

PMID- 19867644
TI  - INTESTINAL OBSTRUCTION : I. A STUDY OF A TOXIC SUBSTANCE PRODUCED IN CLOSED
      DUODENAL LOOPS.
AB  - Closed duodenal loops may be made in dogs by ligatures placed just below the
      pancreatic duct and just beyond the duodenojejunal junction, together with a
      posterior gastro-enterostomy. These closed duodenal loop dogs die with symptoms
      like those of patients suffering from volvulus or high intestinal obstruction.
      This duodenal loop may simulate closely a volvulus in which there has been no
      vascular disturbance. Dogs with closed duodenal loops which have been washed out
      carefully survive a little longer on the average than animals with unwashed
      loops. The duration of life in the first instance is one to three days, with an
      average of about forty-eight hours. The dogs usually lose considerable fluid by
      vomiting and diarrhea. A weak pulse, low blood pressure and temperature are
      usually conspicuous in the last stages. Autopsy shows more or less splanchnic
      congestion which may be most marked in the mucosa of the upper small intestine.
      The peritoneum is usually clear and the closed loop may be distended with thin
      fluid, or collapsed, and contain only a small amount of pasty brown material. The
      mucosa of the loop may show ulceration and even perforation, but in the majority
      of cases it is intact and exhibits only a moderate congestion. Simple intestinal
      obstruction added to a closed duodenal loop does not modify the result in any
      manner, but it may hasten the fatal outcome. The liver plays no essential role as
      a protective agent against this poison, for a dog with an Eck fistula may live
      three days with a closed loop. A normal dog reacts to intraportal injection and
      to intravenous injection of the toxic substance in an identical manner. Drainage
      of this loop under certain conditions may not interfere with the general health
      over a period of weeks or months. Excision of the part of the duodenum included
      in this loop causes no disturbance. The material from the closed duodenal loops
      contains no bile, pancreatic juice, gastric juice, or split products from the
      food. It can be formed in no other way than by the activity of the intestinal
      mucosa and the growth of the intestinal bacteria. This material after dilution,
      autolysis, sterilization, and filtration produces a characteristic effect when
      introduced intravenously. When in toxic doses it causes a profound drop in blood
      pressure, general collapse, drop in temperature, salivation, vomiting, and
      profuse diarrhea, which is often blood-stained. Splanchnic congestion is the
      conspicuous feature at autopsy and shows especially in the villi of the duodenal
      and jejunal mucosae. Adrenalin, during this period of low blood pressure and
      splanchnic congestion, will cause the usual reaction when given intravenously,
      but applied locally or given intravenously it causes no bleaching of the engorged
      intestinal mucosa. Secretin is not found in the duodenal loop fluid, and the loop
      material does not influence the pancreatic secretion. Intraportal injection of
      the toxic material gives a reaction similar to intravenous injection.
      Intraperitoneal and subcutaneous injections produce a relatively slow reaction
      which closely resembles the picture seen in the closed duodenal loop dog. In both
      cases there is a relatively slow absorption, but the splanchnic congestion and
      other findings, though less intense, are present in both groups. There seems,
      therefore, to be no escape from the conclusion that a poisonous substance is
      formed in this closed duodenal loop which is absorbed from it and causes
      intoxication and death. Injection of this toxic substance into a normal dog gives
      intoxication and a reaction more intense but similar to that developing in a
      closed-loop dog.

PMID- 19867645
TI  - INTESTINAL OBSTRUCTION : II. A STUDY OF A TOXIC SUBSTANCE PRODUCED BY THE MUCOSA
      OF CLOSED DUODENAL LOOPS.
AB  - The blood of closed duodenal loop dogs is not toxic to normal dogs. The blood of
      dogs that have been fatally poisoned with duodenal loop fluid is likewise non
      toxic to normal dogs. The mucosa of closed or drained duodenal loops contains a
      toxic substance quite similar to the toxic material found in the lumen of the
      closed loops. This toxic substance is absorbed from the mucosa itself and not
      from the lumen of the drained loops. The same is probably true of the closed
      loops which have an intact mucosa. It seems highly probable that the poison is
      formed by the mucosa and is in great part absorbed directly from it by the blood.
      Normal intestinal mucosa contains no toxic substance nor can it neutralize in
      vitro the toxic substance produced in the closed loops. There is no evidence that
      the toxic material when given intravenously is excreted by the intestine or held
      by the intestinal mucosa in any demonstrable form. The toxic substance is not
      absorbed from the normal intestinal tract. Destruction of the mucosa in a closed
      loop by means of sodium fluoride prevents the formation of the toxic substance.
      This fact furnishes the final proof that the mucosa is the essential factor in
      the elaboration of the poisonous material.

PMID- 19867646
TI  - THE EXTRACELLULAR RELATION OF THE MALARIAL PARASITE TO THE RED CORPUSCLE, AND ITS
      METHOD OF SECURING ATTACHMENT TO THE EXTERNAL SURFACE OF THE RED CORPUSCLE.

PMID- 19867647
TI  - THE INFLUENCE OF LECITHIN AND CHOLESTERIN UPON THE GROWTH OF TUMORS.
AB  - 1. Cholesterin, whether suspended in dilute alcohol or in sodium oleate solution,
      when injected directly into tumors causes a marked acceleration both of the
      primary and of the metastatic growth. 2. The acceleration of the growth of the
      primary tumor by cholesterin is most evident in the premetastatic stage. 3.
      Lecithin, when injected in the form of an aqueous emulsion directly into tumors,
      diminishes the tendency to form metastases, retards the metastatic growth when it
      does occur, and in some instances also retards the primary growth. 4. The
      retardation due to lecithin is most evident in the metastatic stage. 5.
      Simultaneous injection of M/6 strontium chloride solution into the tumors does
      not appreciably affect the action of the lecithin.

PMID- 19867648
TI  - PNEUMONIC LESIONS MADE BY INTRABRONCHIAL INSUFFLATION OF NON-VIRULENT
      PNEUMOCOCCI.
AB  - The intrabronchial insufflation of a non-virulent pneumococcus causes, like the
      insufflation of a virulent pneumococcus, the development of an exudate in the
      lungs which, in general, leaves the framework unaffected, and the lesion presents
      the gross appearance of a lobar pneumonia. It differs, however, materially from
      the pneumonia produced by virulent pneumococci in the important points that the
      consolidation tends to a more rapid resolution, the disease is non-fatal, the
      blood is not invaded by the organism, and the exudate is strikingly poor in
      fibrin. As to the question which was the starting point for the foregoing
      investigation, namely, whether the pneumonic lesion produced by the streptococcus
      is merely a form of pneumonia caused by a less virulent organism, it may be
      answered for the dog, it seems, in the negative. The leucocytic infiltration of
      the framework of the lungs which occurs invariably in streptococcus pneumonia,
      and which is practically absent in the lesions caused by the virulent as well as
      by the non-virulent pneumococcus, is a strong enough feature to form a dividing
      line between the two forms of experimental pneumonia previously described.

PMID- 19867649
TI  - AN EXPERIMENTAL STUDY OF BONE AND JOINT TUBERCULOSIS.
AB  - While one can not assert that the conclusions which experiments appear to offer
      must of necessity correspond to the conditions which arise clinically in man,
      nevertheless these results, if definite, must tend to show the direction in which
      the truth lies. The conclusions which may be drawn from this research are as
      follows: 1. Direct infection of the medulla of a long bone is unlikely to lead to
      the development of a tuberculous osteomyelitis. 2. Inoculation of the interior of
      a joint with tubercle bacilli readily produces tubercle of the synovial membrane.
      3. From such an infected joint the epiphysis or metaphysis of the bone becomes
      diseased. 4. Infection of the arterial heart blood does not result in the local
      development of tubercle of the bones or joints. 5. Infection of the main artery
      supplying a limb leads to the development of tuberculous disease of certain of
      the joints of that limb. 6. Direct infection of the nutrient artery does not
      result in tuberculous osteomyelitis of the bone.

PMID- 19867650
TI  - THE SELECTIVE BACTERICIDAL ACTION OF STAINS CLOSELY ALLIED TO GENTIAN VIOLET.

PMID- 19867651
TI  - THE METAMORPHOSIS OF THE ENDOSTYLE (THYROID GLAND) OF AMMOCOETES BRANCHIALIS
      (LARVAL LAND-LOCKED PETROMYZON MARINUS (JORDAN) OR PETROMYZON DORSATUS (WILDER)).
AB  - The first specimen of Ammocoetes branchialis that showed histologically any
      atrophic changes in the endostyle was taken on July 16. These changes proceeded
      relatively rapidly for about a month, after which the endostyle as such was no
      longer recognized. All specimens examined after August 15 showed in cross section
      the characteristic ductless follicles more or less completely formed. More
      gradual and minor changes in the way of further absorption of cell remnants and
      completion of the follicles continued at least until September 1. Two specimens
      taken from the creek on September 4, 1911. showed complete follicle formation
      with some stainable colloid (figures 14 and 15). There was still yellow granular
      pigment in the fibrous tissue between the follicles. In two specimens taken on
      October 14, 1909, the pigment was absent and the follicles were more closely set,
      larger, and contained homogenous colloid. In the twenty-four specimens of
      ammocoetes studied, there were variations in the time of the onset of
      metamorphosis. There may also be variations in the rate of progress of the
      changes in different specimens. There is no evidence that removal of the animals
      from their native environment to the laboratory either increases or decreases the
      rate of metamorphosis. Schneider states that he was unable to get specimens kept
      in the laboratory to undergo metamorphosis. Gage, however, has repeatedly
      observed the metamorphosis under laboratory conditions, and the six of our
      specimens kept in the laboratory-some for forty days-remained in excellent
      condition and the metamorphosis proceeded as well as in those living in the
      creek. I know of no observations bearing on the question as to whether the
      metamorphosis may be hastened or delayed as it can be in tadpoles and other
      amphibia. It is probable, however, that physical conditions greatly influence the
      transformation. These observations as to the length of time from the inception to
      the completion of metamorphosis indicate that a month and probably longer is
      necessary for the lake and brook lampreys of Central New York. This is in
      agreement with the observations of Gage and of Muller on metamorphosis in
      general, but is at variance with the views of Bujor, who states that the process
      takes place within three to four days. The first endostylar changes are a gradual
      shrinkage in the whole organ with thickening of the capsule and septum and
      proliferation of the connective tissue in the periendostylar zone. The tongue
      anlage is developed in this thickening just dorsal to the endostyle and anterior
      to the gland orifice. The size of the chambers progressively decreases and with
      the thickening of the septum the halves of the endostyle are both absolutely and
      relatively more separated. All the five types of epithelia are affected, the
      first to show the change being type I, the four fan-shaped bundles of cuneiform
      cells of each half of the endostyle. These disappear totally quite early. The
      next type to show marked changes is type III, or the cells with yellow pigment
      granules. Here the change is progressive and these cell groups in different
      stages of atrophy may be traced through to the fully developed follicles. The
      epithelium of type V, or the endothelial-like lining of the parietal walls of the
      chambers, is piled up and extruded laterally as the chambers contract or shrink.
      These cells in different stages of atrophy may be followed until the
      metamorphosis is nearing completion. It is certain that the cells of types I,
      III, and V play no part in the formation of the ductless follicles. With types II
      and IV the question is not so easily settled as it is from one or the other or
      from both of these types that the permanent follicles arise. One can say
      definitely that type IV plays the major role, but whether the cells of type II
      after fusion with the basal group of type IV do not also share in the formation
      of the ventral follicle of the given chamber, I cannot decide, but from the
      evidence obtainable this seems probable. It is significant that the cells of type
      IV are continuous with, and indistinguishable from, the cells lining the orifice
      and are continued anteriorly in the deep pharyngeal groove and peripharyngeal
      grooves as well as posteriorally from the orifice in the small pharyngeal groove.
      As to the fate of this extraglandular epithelium of type IV I have no data save
      that with the closing of the orifice and the formation of the permanent branchial
      sac these grooves with their ciliated epithelium disappear and the whole sac
      comes to be lined with plain stratified epithelium. The fact that the cells of
      the pharyngeal grooves and the lining cells of the gland orifice are continuous
      with the cells of the endostyle from which the permanent thyroid follicles are
      formed is not without significance in relation to the development of the thyroid
      of the higher chordates. One or more very large follicles are formed from the
      lower portion of this orificial epithelium of type IV. Four ductless follicles
      are the maximum number that may be formed primarily in each half of the endostyle
      from the four areas of epithelium of type IV. From the specimens studied this
      maximum is frequently not obtained. Posterior to the orifice where four chambers
      exist, each corresponding to one half of an anterior chamber, but two follicles
      may be formed from each chamber, but in the coil these are proportionately
      increased, in cross section. Most of the detailed studies here recorded have been
      made on the part of the endostyle posterior to the coil where the simplest
      conditions exist. Here two follicles are ordinarily formed from each chamber. In
      cross sections the follicles are at first only long tubules whose cavities are
      the remnants of the original endostyle chambers, but when the metamorphosis is
      completed each of these primary tubules is cut up into several elongated closed
      sacs corresponding to the true ductless follicles of all higher chordates. New
      follicles also arise by budding from these primary ones, and this process is
      probably of normal occurrence at the metamorphosis.

PMID- 19867652
TI  - ON THE POSSIBLE IMPORTANCE OF COLLOIDAL PROTECTION IN CERTAIN PHASES OF THE
      PRECIPITIN REACTION.

PMID- 19867653
TI  - THE RELATION OF THE LEUCOCYTIC BACTERIOLYSIN TO BODY FLUIDS.
AB  - 1. An extract of horse leucocytes is strongly bactericidal when dissolved in
      distilled water; it has considerable bactericidal power when dissolved in
      physiological saline; but it loses its bactericidal properties when mixed with
      blood serum or with normal or pathological tissue fluids. 2. About half the
      antibactericidal action of blood serum is due to the serum colloids, about a
      quarter to the neutral serum crystalloids, and a quarter to the diffusible
      alkalies. Diffusible acids have no antibactericidal action. 3. The addition of
      boric acid to an inactive mixture of leucocytic extract and serum or other body
      fluid occasionally restores part of the original bactericidal power, but never
      more than a small fraction of that power.

PMID- 19867654
TI  - THE REACTION OF THE LUNGS TO THE INTRABRONCHIAL INSUFFLATION OF KILLED VIRULENT
      PNEUMOCOCCI AND OF PLAIN STERILE BOUILLON.
AB  - The experiments show that intrabronchial insufflation of a culture of virulent
      pneumococcus killed by heat and still containing stainable organisms produces an
      inextensive, mild, patchy, superficial inflammation of the lung tissue bearing no
      similarity to the lesions produced by the living pneumococcus, and that
      insufflation of sterile bouillon causes a pronounced congestion of the lung
      tissue with which it comes in contact, sometimes lasting for forty-eight hours.

PMID- 19867655
TI  - THE INFLUENCE OF THE VAGUS NERVES ON THE FARADIZED AURICLES IN THE DOG'S HEART.
AB  - An abnormal auricular activity is produced by faradization of the right auricle
      of the dog, which frequently becomes established and continues for varying
      periods of time after faradization is discontinued. This auricular activity
      consists of a rapid auricular tachycardia coexisting with true auricular
      fibrillation. In some dogs the auricles are thrown into this abnormal activity
      more readily by faradization after the vagi have been cut than before. Cutting
      the nerves has little or no effect on the abnormal auricular activity, but the
      ventricular rate may be much increased if the vagi are cut after the abnormal
      auricular activity has been established, apparently because of an improvement in
      the auriculoventricular conductivity. Stimulation of the right vagus nerve
      changes the character of the activity of the faradized auricles by inhibiting the
      auricular tachycardia while the fibrillation is uninfluenced. Stimulation of the
      left vagus nerve has little or no apparent inhibitory effect on the auricular
      tachycardia, but has possibly an inhibitory effect on the auricular fibrillation.
      Vagus stimulation increases the susceptibility of the auricles to faradization.
      The abnormal activity set up by faradization may be established in hearts
      otherwise refractory by vagus stimulation of short duration following the
      faradization. Vagus stimulation usually holds the auricles in the abnormal
      activity set up by faradization as long as it is continued in hearts in which,
      without vagus stimulation, the sequential beat always returns as soon as
      faradization is stopped. The right vagus is more effectual in this respect than
      the left. In some hearts vagus stimulation alone is capable of initiating the
      same abnormal auricular activity which is caused by auricular faradization. The
      normal sequential beat is often restored by vagus stimulation. It replaces the
      abnormal auricular activity not during, but a few seconds after, the termination
      of vagus stimulation. Left vagus stimulation is somewhat more effectual in
      producing this result than right vagus stimulation.

PMID- 19867656
TI  - FURTHER STUDIES ON THE CHEMISTRY OF BLOOD SERUM.
AB  - The following conclusions may be drawn from the results obtained in this study.
      1. In the minor surgical cases (considered normal) the chemical composition of
      the blood serum agrees, as far as its proteins are concerned, with the usual
      standard values. When examined at different times, the serum of such cases shows
      no variation in the total protein content or in its individual fractions. The
      incoagulable nitrogen, however, varies considerably in the total amount in the
      different cases, as well as in its percentage relations to the other constituents
      of the serum. 2. The cases of prostatic hypertrophy, with or without chronic
      interstitial nephritis, show no change from the normal in the character of the
      protein composition of the serum, nor in the ratio which the individual fractions
      bear to each other. On the other hand, the incoagulable and non-protein nitrogen
      of the serum show marked fluctuations, some of which correspond to the degree of
      functional deficiency of the kidneys. 3. In cases of localized infections of the
      kidneys, the changes in the blood serum are twofold. One concerns the proteins,
      and is traceable to the infection; and the other concerns the non-protein
      nitrogen, results from functional impairment, and varies with the amount of
      destruction of the kidney substance. Thus an increase in the globulins is
      observed in these sera similar to that occurring in infections in other
      localities; the non-protein content increases apparently in direct proportion to
      the degree of deficiency of the kidney, and becomes diminished when the function
      of the kidneys improves.

PMID- 19867657
TI  - STUDIES IN FERMENT ACTION : VII. TOXIC SPLIT PRODUCTS OF BACILLUS TYPHOSUS.
AB  - 1. A single intravenous injection into dogs of a sufficient number of freshly
      washed typhoid bacteria produces the symptoms and pathology that characterize
      anaphylaxis in these animals. 2. These effects are not produced by the coagulable
      protein-free filtrate from a fresh emulsion, while a similar filtrate from an
      emulsion digested with leucoprotease is very potent, the toxic portion of the
      bacterial bodies being changed from a coagulable to a non-coagulable state. 3.
      The symptoms and pathology described are not specific, since they can be produced
      by substances other than typhoid toxins. 4. Digestion with leucoprotease
      furnishes a method of liberating toxic substances from typhoid bacteria
      resembling the processes of nature more closely than the methods heretofore used.
      5. The toxic substances thus liberated are not destroyed by a heat and acid
      precipitation of the coagulable proteins, and are of the nature of primary
      proteoses.

PMID- 19867658
TI  - A TRANSPLANTABLE NEW GROWTH OF THE FOWL, PRODUCING CARTILAGE AND BONE.
AB  - An osteochondrosarcoma of the common fowl, designated in this laboratory as
      Chicken Tumor VII, has been successfully transplanted to seven successive series
      of hosts. The original growth contained bone and cartilage, was attached to the
      sternal keel of an otherwise healthy chicken, and appeared to have arisen from
      this structure. In the growths derived from its transplantation cartilage is
      regularly laid down, followed later by bone in case the host lives long enough.
      The prechondral tissue consists of spindle-shaped or multipolar cells of the
      fibroblast type. The histological character and the behavior of this prechondral
      tissue show that it is sarcomatous, a fact further proven by one recent case in
      which the tumor has metastasized. The secondary growth in this instance consisted
      of prechondral tissue in which a cartilaginous change was taking place. The tumor
      could not be transferred to pigeons, the one foreign species tested, but grew
      readily in chickens of two alien breeds. Reinoculation experiments suggest the
      occurrence of a natural, individual immunity, and of a certain degree of acquired
      resistance. In one fowl visceral growths developed following an intravenous
      injection of tumor emulsion, although whether they were due to this cause or were
      secondary to the large implantation growths in the muscles is uncertain. Recently
      the tumor has been transmitted by means of the filtrate from a Berkefeld filter.

PMID- 19867659
TI  - TRANSPLANTABILITY OF TISSUES TO THE EMBRYO OF FOREIGN SPECIES : ITS BEARING ON
      QUESTIONS OF TISSUE SPECIFICITY AND TUMOR IMMUNITY.
AB  - Inoculation of the Jensen rat sarcoma into the developing chick embryo gives a
      rapidly growing tumor at the site of inoculation, whether in the membranes or in
      the body of the chick itself. These tumors by transfer from embryo to embryo can
      be kept going for as long as forty-six days, and perhaps indefinitely in the
      foreign species. The rat cells show no morphological change even after a very
      long dependence. Their biological characters are also retained, as is shown by
      the fact that the cells when replanted in the rat, after a prolonged sojourn in
      the chick, will produce a rapidly growing sarcoma of the Jensen type. These rat
      tissues grown for long periods in the chick show no adaptation to the new
      species, being destroyed even more rapidly when placed in the adult chicken than
      cells taken directly from the rat. Morphologically the cells retain a close
      resemblance to those in the original tumor. Other tissues grown in chick embryo
      are various embryonic cells from the chicken, mouse, and rat, the Ehrlich sarcoma
      and chondroma of the mouse, a mammary carcinoma of the mouse, the Flexner-Jobling
      adenocarcinoma of the rat, and a human sarcoma.

PMID- 19867660
TI  - FALSE TRANSITIONS BETWEEN NORMAL AND CANCEROUS EPITHELIUM.

PMID- 19867661
TI  - COMPARATIVE STUDIES UPON CANCER CELLS AND NORMAL CELLS : II. THE CHARACTER OF
      GROWTH IN VITRO WITH SPECIAL REFERENCE TO CELL DIVISION.
AB  - 1. In primary cultures sarcoma cells exhibit a much greater activity than do
      normal connective tissue cells grown from the adult blood vessel; there is a
      shorter latent period, ameboid phenomena are more marked, and cell multiplication
      proceeds more rapidly. 2. In secondary cultures sarcoma cells are less active
      than in primary cultures; connective tissue cells, on the other hand, show a
      markedly accelerated growth. 3. Connective tissue cells are more easily
      propagated over long periods in vitro than are sarcoma cells; they multiply
      actively in cultures more than three months old. 4. The method of tissue
      cultivation is well adapted to the study of normal and pathological cell
      division; the nuclear changes are easily discernible in the living cell as
      division proceeds, and staining methods may be applied to verify observations
      upon the unstained structures. 5. Atypical mitoses of several kinds are found in
      cultures of sarcoma cells but are not seen in growths of connective tissue. 6.
      The time required for division in rat connective tissue cells kept at body
      temperature (38 degrees C.) varies within relatively narrow limits (twenty to
      fifty minutes); sarcoma cells, on the contrary, exhibit marked variations and
      several hours may be required. 7. In studies upon living cells amitotic division
      has not been observed in either normal or tumor tissue. Evidences of nuclear
      budding, however, with the formation of cells containing several nuclei of
      irregular size have been noted.(3) The development of a cell with two nuclei from
      a mononuclear cell by mitotic division of the nucleus without division of the
      cytoplasm has also been observed.

PMID- 19867662
TI  - THE BACTERIOLOGY AND VACCINE THERAPY OF DISTEMPER IN HORSES.

PMID- 19867663
TI  - EXPERIMENTS ON THE TRANSMISSION OF SCARLET FEVER TO THE LOWER MONKEYS.
AB  - 1. The reported successful transfer of scarlet fever to both higher and lower
      monkeys is not definitely established. 2. In the course of the experiments here
      reported, the infectious agent can be assumed to have been carried over to the
      monkeys. The failure to cause infection probably proceeds from the
      insusceptibility of the monkeys employed, or to the manner of introducing the
      agent. 3. The temperature curve and leucocyte count of monkeys are unsatisfactory
      criteria for the diagnosis of disease in those animals. 4. Monkeys frequently
      have transient blotchy, erythematous eruptions on the face and neck, and almost
      always a bran-like desquamation. 5. Monkeys are highly resistant to infection
      with microorganisms from human beings.

PMID- 19867664
TI  - EXPERIMENTAL PULMONARY TUBERCULOSIS IN THE DOG : THE EFFECT OF LARGE AMOUNTS OF
      TUBERCLE BACILLI OF BOVINE TYPE INTRODUCED DIRECTLY INTO THE LUNGS BY WAY OF THE
      AIR PASSAGES.
AB  - It is obvious, as stated in the beginning, that these experiments have failed to
      reproduce a chronic pulmonary tuberculosis. Acute pneumonic processes of
      tubercular origin are, however, not infrequent as a complicating or terminal
      process in pulmonary phthisis, and there have been several cases described in
      which individuals have died with the symptom complex of acute lobar pneumonia, in
      which it developed at post-mortem examination that the disease was tuberculosis.
      Our experiments throw some light on debated questions in connection with these
      acute pneumonic forms of phthisis. In our experiments we believe that we have
      effectively reproduced this exudative type of tuberculosis of the lungs. This
      type of lesion may, in the light of our experiments, result from the sudden
      bronchogenic invasion of large numbers of virulent tubercle bacilli in a
      relatively resistant animal. The large mononuclear cells so frequently
      encountered in the exudate seem to be brought there chiefly from outside.(1) As
      Orth found when studying human material, it is difficult here also, to exclude
      the possibility that similar cells may result from the desquamation of alveolar
      epithelium. The tubercle bacillus alone, without the aid of secondary infection,
      is competent to produce a type of lesion which leads to necrosis of the bronchi,
      and by discharge of the necrotic material to cavity formation. As judged by our
      experiments the bronchi are less resistant to involvement in the necrosis than
      are the blood vessels or pleural surfaces. The fact that by the method of
      bronchial insufflation of Lamar and Meltzer a characteristic tuberculous
      pneumonia may be produced makes it probable that the lobar pneumonias generally
      are of bronchogenic origin.

PMID- 19867665
TI  - THE ANTIGENIC PROPERTIES OF GLOBIN CASEINATE.
AB  - This study of globin and its compound with casein (globin caseinate) shows that
      globin fails to produce fixation antibodies in rabbits after repeated injections,
      thus agreeing with our own work and with that of others with similar histon
      bodies which are primarily toxic. When globin is combined with casein, however,
      it gives rise to antibodies that react not only with globin caseinate and casein
      but also with globin. The antibodies in antiglobin casein serum are apparently
      separate, one for globin and one for casein. In other words, the change in globin
      undergone on combination with casein has apparently rendered it antigenic. We did
      not succeed in demonstrating the genesis of this new antigenic property by
      anaphylaxis experiments. A further investigation of similar and more complex
      combined proteins is indicated and gives promise of more light on the nature of
      biological specificity.

PMID- 19867666
TI  - THE RENAL LESION OF EXPERIMENTAL CANTHARIDIN POISONING.
AB  - Although the study of experimental nephritis by physiological methods shows that
      the most striking effect of cantharidin is injury of the blood vessels, the great
      abundance of mitotic figures in the tubular epithelium in the stage of repair
      points to an equally widespread and severe epithelial injury. Caution must
      therefore be observed in ascribing the physiological disturbances of kidney
      function caused by cantharidin as due exclusively to a vascular injury, and in
      regarding cantharidin nephritis as a pure type of vascular nephritis.

PMID- 19867667
TI  - THE VALUE OF MALLORY'S CONNECTIVE TISSUE STAIN FOR THE DEMONSTRATION OF VARIATION
      IN THYROID COLLOID.
AB  - 1. Mallory's connective tissue stain used in connection with fixation of tissue
      by Zenker's fluid or bichloride of mercury demonstrates the presence or absence
      of iodin in the thyroid colloid, as is evidenced by parallel chemical
      determinations, iodin feeding, and test-tube experiments. 2. Greatly increased
      activity of the heart is accompanied by a loss of thyro-iodin from the colloid of
      the thyroid. 3. This method, while apparently not adaptable to clinical use, may
      prove of value in further experimental work on the thyroid.

PMID- 19867668
TI  - THE RESULTS OF THE SERUM TREATMENT IN THIRTEEN HUNDRED CASES OF EPIDEMIC
      MENINGITIS.
AB  - The data brought together in this report have been gathered from a wide territory
      and for a period extending over several years. The antimeningitis serum was first
      employed in 1906 and the latest figures relating to its use included in this
      report were furnished in 1912. There is no longer doubt that the serum has come
      to be applied under conditions fairly representing all known manifestations of
      epidemic meningitis. Hence the test of the serum treatment may be regarded as
      having been a rigorous one. The initial difficulties surrounding the
      administration by direct subdural injection have been largely overcome and
      doubtless will be still further mastered. Already the serum is being successfully
      applied in private as well as in hospital practice. This gain will probably be
      reflected in a still further diminution of the mortality since early injection
      plays such a large part in determining the results achieved. The 1,300 cases
      studied in this report are a part only of a far greater number of cases actually
      treated with the serum supplied by the Rockefeller Institute. It was not found
      possible to secure histories of all the cases treated; but there is no reason to
      suppose that the results of the analysis would have been essentially different if
      reports of a still larger number of cases had been returned. The decision arrived
      at is not based upon statistical computations alone, but upon objective data as
      well that are not readily misinterpreted. The conclusion that follows was first
      stated in 1909 as the result of an analysis of 400 serum-treated cases. It is
      supported by the study of the larger series of cases just presented. "In view of
      the various considerations presented, the conclusion may be drawn that the
      antimeningitis serum, when used by the subdural method of injection, in suitable
      doses and at proper intervals, is capable of reducing the period of illness; of
      preventing, in large measure, the chronic lesions and types of the infection; of
      bringing about complete restoration of health, in all but a very small number of
      the recovered, thus lessening the serious, deforming, and permanent consequences
      of meningitis; and of greatly diminishing the fatalities due to the disease."

PMID- 19867670
TI  - THE IMMUNIZATION OF LARGE ANIMALS TO A PATHOGENIC TRYPANOSOME (TRYPANOSOMA
      HIPPICUM (DARLING)) BY MEANS OF AN AVIRULENT STRAIN.

PMID- 19867669
TI  - PARALYSIS IN A DOG SIMULATING POLIOMYELITIS.
AB  - A pet dog developed a form of paralysis simulating the paralysis of epidemic
      poliomyelitis. The autopsy showed changes in the spinal cord and intervertebral
      ganglia, resembling, but not identical with, the lesions of poliomyelitis in man.
      Inoculation of the affected spinal cord into the nervous system of young dogs and
      Macacus rhesus monkeys was not followed by the production of paralysis or other
      obvious symptom of disease.

PMID- 19867671
TI  - THE ACTION OF PNEUMOCOCCUS ON BLOOD.
AB  - The reduction of the oxygen capacity which occurs after incubating pneumococcus
      cultures with washed rabbit corpuscles is due to the formation of methemoglobin
      (or some derivative of hemoglobin with identical optical constants for three
      regions in the spectrum). The substance which induces the change is also present
      in the sterile filtrate of autolyzed cultures. By analogy we feel justified in
      concluding that the mechanism of the reduction of the oxygen capacity in human
      lobar pneumonia is at least in part of the same nature. To determine the
      frequency and intensity of the phenomenon in lobar pneumonia, and thereby to
      establish its clinical significance, is the next step and a problem upon which we
      are now engaged.

PMID- 19867672
TI  - HEMATOGENOUS AND OBSTRUCTIVE ICTERUS : EXPERIMENTAL STUDIES BY MEANS OF THE ECK
      FISTULA.
AB  - Normal and Eck fistula dogs react in a similar manner to the intravenous
      injection of hemoglobin obtained from laked red cells of the same animal.
      Hemoglobin appears in the urine after a few minutes and bile pigments in one to
      one and one half hours. In this simple type of hematogenous jaundice the reaction
      is in no way influenced by shutting out the portal blood from the liver and
      cutting down its blood supply to about 25 per cent. of normal. In a second type
      of hematogenous jaundice produced by chloroform anesthesia, which produces
      central liver necrosis, there is no essential difference between the normal and
      Eck fistula dog. The Eck fistula dog, as a rule, is more resistant to this
      poison, but, given a definite liver necrosis, the jaundice developing will reach
      its maximum on the second day as in the normal animal. This jaundice must be
      explained in part by capillary biliary obstruction, but in part by a hemolysin
      formed in the injured liver cells (Joannovics and Pick). Simple obstruction of
      the common duct when combined with an Eck fistula gives rise to a definite low
      grade icterus with bile pigment constantly present in the urine. Under these
      conditions after doubly ligating and cutting the common duct with separation of
      the cut ends, the lumen of the duct may be established and bile may enter the
      intestine by means of a fistulous tract between the cut ends of the bile duct.
      The formation of bile and bile pigments is much less in an Eck fistula dog than
      in a normal animal and consequently the icterus is much less intense. This is
      probably due to a lessened activity of the liver cells because of decreased blood
      supply. This observation does not harmonize with the current view that bile
      pigments are formed solely from hemoglobin, as there is no evidence of more
      hemolysis in a normal than in an Eck fistula dog. This suggests that the bile
      pigment may be formed in part, at least, from other substances than hemoglobin,
      and, further, that bile pigment formation normally may depend in part upon the
      functional activity of the liver cell rather than upon the amount of hemoglobin
      supplied to it.

PMID- 19867673
TI  - ICTERUS : A RAPID CHANGE OF HEMOGLOBIN TO BILE PIGMENT IN THE CIRCULATION OUTSIDE
      THE LIVER.
AB  - The intravenous injection of red cells obtained from the same animal and laked by
      distilled water is similar to certain types of hemolysis which result in
      hematogenous jaundice. This procedure cannot be criticized on the grounds of
      introducing toxic substances. The hemoglobin circulating in the blood stream is
      rapidly changed, in part at least, to bile pigment. The change goes on with
      practically the same rapidity in a normal circulation, in an Eck fistula animal,
      and in a dog with Eck fistula and hepatic artery ligation. Moreover, the bile
      pigment formation goes on in a dog whose liver, spleen, and intestines have been
      shut out of the circulation, and in those with a head and thorax circulation. In
      the last experiments there had been no operative manipulation of the liver and
      the bile pigment could not have escaped from the liver and have been absorbed by
      the circulation above the diaphragm; for example, by the thoracic duct. It is
      possible that the endothelium of the blood vessels is the agent which brings
      about the rapid change of hemoglobin to bile pigment. This mechanism probably
      comes into play when there has been a destruction of many red cells with much
      hemoglobin free in the plasma. We may conclude that in dogs, at least, hemoglobin
      can be rapidly changed into bile pigment in the circulating blood without
      participation of the liver.

PMID- 19867674
TI  - MORPHOLOGICAL STUDIES IN EXPERIMENTAL CRETINISM.
AB  - In summarizing the findings of this paper it may be said that degenerative
      changes have been noted in practically every parenchymatous organ. Among these
      the most striking has been that of serous imbibition by the most active cells of
      these organs. In regard to the changes in the glands of internal secretion, the
      findings corroborate the statements of Cushing in regard to hypophysectomy, that
      removal of one gland of internal secretion results in changes in all the other
      glands. In this case, degenerative changes predominate in the hypophysis, thymus,
      ovary, and testis, while hyperplasia is seen in the islands of Langerhans and the
      medullas of the adrenal glands. Finally, in the rabbit athyroidism is responsible
      for grave degenerative changes in practically all organs and tissues of the body,
      and many of the symptoms of cretinism have an anatomical basis in organic
      cellular changes.

PMID- 19867675
TI  - A NOTE ON THE BEHAVIOR OF THE SAPROPHYTIC COCCI WITH REGARD TO GRAM'S STAIN.

PMID- 19867676
TI  - STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : PARTS I TO III.

PMID- 19867678
TI  - ON THE COMPONENTS OF SPHINGOMYELIN.

PMID- 19867677
TI  - STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : IV. Is THERE A PARALLELISM
      BETWEEN THE TRYPANOCIDAL AND PNEUMOCOCCICIDAL ACTION OF DRUGS?

PMID- 19867679
TI  - THE OXYGEN CONTENT OF THE BLOOD IN RABBITS INFECTED WITH PNEUMOCOCCUS.
AB  - In rabbits with a severe pneumococcus bacteremia, the oxygen-combining power of
      the blood falls progressively up to the time of death. Coincident with this there
      is an even more marked fall in the oxygen content of the arterial blood. The
      changes in the blood in infected animals are analogous to those seen when the
      pneumococcus is grown on blood in vitro. They are due to the conversion of
      hemoglobin into methemoglobin.

PMID- 19867680
TI  - THE EFFECT OF HEMATIN ON THE CIRCULATION AND RESPIRATION.
AB  - 1. Doses of less than six milligrams of hematin and, under certain conditions,
      larger doses may cause a slight rise of blood pressure. 2. Large doses of hematin
      cause a profound and prolonged fall of blood pressure. The principal factor in
      this fall of blood pressure is the marked dilatation of the splanchnic vessels.
      The splanchnic dilatation either does not occur at all or but very slightly if
      the splanchnic nerves are cut. The splanchnic dilatation is partly compensated
      for by a marked constriction of cutaneous vessels and it seems probable that the
      cutaneous constriction is active and not simply passive to the splanchnic
      engorgement. 3. Hematin acts upon the cardio-inhibitory center causing a marked
      slowing of the rate of heart-beat, and in large doses produces a typical vagal
      pulse or even marked irregularities in the amplitude and rhythm of the pulse.
      Under hematin the heart at first shows great loss of tone but later the tone
      increases beyond the normal. The cardiac output for a time is greatly diminished.
      4. In the large doses employed by us, hematin depresses the respiratory center
      and death under hematin is due to paralysis of this center.

PMID- 19867681
TI  - CONCERNING AGGLUTININS FOR TREPONEMA PALLIDUM.
AB  - 1. There is no demonstrable amount of agglutinin for Treponema pallidum (Noguchi)
      in normal human and normal rabbit serum in dilutions as low as 1:20. 2.
      Agglutinins for Treponema pallidum are readily produced in young rabbits by the
      administration of pure cultures of living spirochetes. 3. There is no appreciable
      amount of agglutinin for Treponema pallidum culture used in the sera of secondary
      and tertiary syphilis or in the cerebrospinal fluid of tertiary syphilis in
      dilutions of 1:20 to 1:640.

PMID- 19867682
TI  - INTESTINAL OBSTRUCTION IN THE RABBIT. II.

PMID- 19867683
TI  - A STUDY OF THE MECHANICAL OBSTRUCTION TO THE CIRCULATION OF THE KIDNEY PRODUCED
      BY EXPERIMENTAL ACUTE TOXIC NEPHROPATHY.
AB  - 1. Rabbits may have spontaneous nephropathy and show no casts or albumen in the
      urine. 2. If we leave out of consideration rabbits 17, 18, 19, and 20, which were
      perfused with Adler's solution, and rabbits 8, 9, 17, 18, and 28, which were
      injected subcutaneously with potassium chromate, rabbits 49 and 73 show that
      spontaneous nephropathy offers some impediment to the perfusing serum.

PMID- 19867684
TI  - STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : V. THE ROLE OF THE LEUCOCYTE IN
      EXPERIMENTAL PNEUMONIA. THE RELATION OF THE NUMBER OF ORGANISMS INJECTED TO THE
      MORTALITY.
AB  - 1. The importance of the leucocyte in the resistance of animals to experimental
      pneumonia is emphasized by the fact that animals treated with benzol, a
      leucotoxic substance, rapidly succumb to the disease, while animals treated in
      like manner with toluol, a very similar chemical substance causing no leucopenia,
      show no decreased resistance. 2. The role of the leucocyte in the resistance of
      animals to experimental pneumonia is further emphasized by the fact that animals
      that respond to the pneumococcus infection with a leucocytosis, as occurs after
      the repeated injection of toluol, are more resistant to the pneumonia. Further,
      the hyperleucocytosis produced by repeated injection of nutrose before the
      production of pneumonia likewise seems to increase the resistance of the animals.
      3. Experimental pneumonia is not necessarily fatal in rabbits. The factors
      determining the outcome of the disease are numerous; among these is the number of
      bacteria inoculated. Animals receiving small doses usually survive, while those
      receiving comparatively large numbers usually succumb.

PMID- 19867685
TI  - STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : VI. STUDIES IN IMMUNITY.
AB  - 1. Rabbits recovering from one attack of experimental pneumonia possess an active
      immunity. Such animals may subsequently withstand repeated increasing doses of
      pneumococci intratracheally. 2. Death may supervene after any one of subsequent
      injections, but it seems to depend partly upon the chronic changes in the
      cardiorespiratory apparatus. It may at least be said that it is usually
      unassociated with a septicemia which is an invariable accompaniment of fatal
      primary lobar pneumonia. 3. The serum from animals actively immunized by the
      repeated intratracheal inoculations with pneumococci may be used successfully to
      confer a passive immunity against the homologous organism.

PMID- 19867686
TI  - THE OXYGEN CONTENT OF THE BLOOD IN LOBAR PNEUMONIA.
AB  - In most cases of uncomplicated lobar pneumonia the decrease of respiratory
      surface is completely compensated for, and the oxygen content of the blood is
      within normal limits. Occasional cases of uncomplicated pneumonia have an oxygen
      content of the venous blood which is below normal. In the two cases reported
      here, this was associated with a carbon dioxide content of the blood which was
      higher than normally, and the condition was apparently due to an interference
      with the respiratory exchange of gases. In the terminal stage of the fatal cases
      of pneumonia in which death does not occur with great suddenness, there is often
      a progressive diminution in the oxygen content of the blood. Synchronous with
      this is a progressive decrease in the oxygen-combining capacity of the blood.
      These changes are usually seen in patients in whom an intense bacteremia has
      developed and are analogous to those found in the arterial blood of infected
      rabbits, and to those resulting from the growth of the pneumococcus in blood in
      vitro. In all three conditions there is probably a change of oxyhemoglobin to
      methemoglobin. This change of the hemoglobin molecule, so that it no longer takes
      up and gives off oxygen readily, is probably a factor in the immediate cause of
      death in many cases of pneumonia.

PMID- 19867687
TI  - A STUDY OF THE ADDITION OF CHOLESTERIN TO THE ALCOHOLIC EXTRACTS OF TISSUES USED
      FOR ANTIGENS IN THE WASSERMANN REACTION.
AB  - 1. The addition of cholesterin to an alcoholic extract of heart or fetal liver
      increases the antigenic value of the extracts in the Wassermann reaction. 2. The
      optimum amount of cholesterin to be added to heart extract or fetal liver extract
      was found to be 0.4 per cent. 3. Cholesterin-heart extracts are superior to
      cholesterin-liver extracts and to alcoholic extracts of syphilitic livers, as
      well as to ether extracts of dried hearts. 4. Cholesterin-heart extracts prepared
      from different human hearts are practically equal in anticomplementary and
      antigenic value. Similar extracts prepared from guinea pig hearts have the same
      antigenic value as those prepared from human hearts. Both the human heart and the
      guinea pig heart extracts are superior to beef heart extract when the same amount
      of cholesterin is added to each of the extracts. 5. In testing blood serum for
      diagnostic purposes, it is not safe to use more than one fourth of the
      anticomplementary dose of the 0.4 per cent. cholesterin heart extract. In the
      work here presented, this consisted of a 1 in 10 emulsion. 6. In testing
      cerebrospinal fluids, 1 in 10 emulsions give slightly better reactions with
      smaller quantities of the fluid than do 1 in 6 emulsions. 7. Because of the
      simple preparation, the superior antigenic property, and the constant antigen
      value of cholesterin-heart extracts prepared from human hearts, we agree with
      McIntosh and Fildes that this form of extract fulfills the requirements of a
      standard antigen.

PMID- 19867688
TI  - MALARIAL PIGMENT (HEMATIN) AS AN ACTIVE FACTOR IN THE PRODUCTION OF THE BLOOD
      PICTURE OF MALARIA.
AB  - 1. Intravenous injections of alkaline hematin in the rabbit produce an anemia the
      severity of which is proportional to the amount of hematin injected and the
      susceptibility of the animal. 2. Hemoglobinemia is an occasional consequence of
      hematin poisoning. 3. The leucocytes in hematin intoxication are usually
      increased in number and are always characterized by a high percentage of large
      mononuclear cells and by pigmented phagocytes. 4. The platelets are markedly
      reduced by alkaline hematin and ultimately a prolongation of the coagulation time
      of the blood and of the bleeding time results. 5. The anemia, the hemoglobinemia,
      the high percentage of large mononuclear leucocytes, the destruction of
      platelets, and the tendency to hemorrhage in malaria are all influenced by the
      malarial pigment, hematin.

PMID- 19867689
TI  - STUDIES ON THE CIRCULATION IN MAN : VI. OBSERVATIONS ON THE BLOOD FLOW IN THE
      HANDS (MAINLY) IN CASES OF ANEMIA.
AB  - 1. In the cases of anemia studied (pernicious anemia, chlorosis, and secondary
      anemia) the blood flow in the hand is smaller than the normal flow. 2. Accepting
      Plesch's result, that the minute volume of the heart is increased in the anemias,
      the diminution in the hand flow is interpreted as a sign of a vasoconstriction in
      peripheral parts, which facilitates the increased flow through the lungs. 3. The
      deficiency in the hand flow is less in the chlorotic group than in the other
      cases of anemia. The explanation suggested is that the increased total volume of
      the blood in chlorosis permits the normal amount of hemoglobin to circulate
      through the lungs without a marked increase in the peripheral vasoconstriction.
      4. The view that the diminution in the cutaneous blood flow in anemia is a
      necessary compensatory arrangement for increasing the flow through the lungs
      affords a natural explanation of the beneficial effect in many cutaneous
      disorders of general measures, especially those aimed at improving the quality of
      the blood. 5. In a case of bradycardia with a pulse rate permanently below 40
      during rest in a sitting position, the hand flow was normal.

PMID- 19867690
TI  - INTESTINAL OBSTRUCTION.

PMID- 19867691
TI  - AN EXPERIMENTAL STUDY OF THE LATE GLOMERULAR LESIONS CAUSED BY CROTALUS VENOM.
AB  - The acute exudative glomerular lesion of the rabbit's kidney caused by crotalus
      venom does not lead to a subacute or chronic glomerulonephritis. The hemorrhagic
      lesion of the glomerular tuft may show a process of repair characterized by the
      ingrowth, into the hemorrhagic masses, of endothelial cells from the uninjured
      part of the tuft. This process is, however, more analogous to the organization of
      a red thrombus than it is to any form of glomerular lesion known in man, and can
      hardly serve as an experimental demonstration of the mode of development of a
      subacute or chronic glomerular nephritis. On the other hand, crotalus venom
      causes a persistent albuminuria and extensive tubular degeneration and cast
      formation, with death, preceded by great emaciation, after five to six weeks.

PMID- 19867692
TI  - CONCERNING VISCERAL ORGANISMS.

PMID- 19867693
TI  - THE CEREBROSPINAL FLUID IN SYPHILIS.

PMID- 19867694
TI  - THE GROWTH OF TISSUE IN ACID MEDIA.
AB  - Connective tissue cells of chick embryos and cells of a chicken sarcoma,
      proliferating in vitro, soon render acid the plasma about them, but they
      nevertheless continue to grow well. Evidently the tissue cell will withstand a
      considerably greater change in the reaction of the fluids about it than has
      usually been supposed. Under conditions of in vitro life in plasma, which do not
      provide for an artificial circulation, the acid produced by growing tissues
      diffuses only slowly and is subject to little dilution from this source. About
      tissues which grow very rapidly in vitro, as, for example, tumor tissues, there
      must be a marked concentration of metabolic products, and this may largely
      account for the poor results of attempts at the continuous propagation of such
      tissues in vitro.

PMID- 19867695
TI  - THE SELECTIVE BACTERICIDAL ACTION OF METHYLENE-BLUE.

PMID- 19867696
TI  - THE RELATION OF THE RATE OF ABSORPTION OF ADRENALIN TO ITS GLYCOSURIC AND
      DIURETIC EFFECTS.
AB  - Subcutaneous injections of adrenalin are, in contrast with its behavior in the
      production of the other effects of that drug, more favorable to the production of
      glycosuria in rabbits than intramuscular injections; the failures are fewer and
      the quantities of dextrose in the urine are generally larger. In general, as
      regards the stimulation of diuresis by adrenalin, a subcutaneous injection exerts
      generally a greater effect than an intramuscular one. Subcutaneous injections of
      a certain dose of adrenalin distributed over several areas are far less effective
      than the administration of that dose in a single injection; they fail frequently
      to produce any glycosuria, the quantity of dextrose in the urine, when present,
      being less, and the quantity of urine being generally diminished. Apparently the
      more slowly the injected adrenalin reaches the blood, the greater is its effect
      in producing glycosuria and generally, also, the greater its diuretic action.

PMID- 19867697
TI  - A CONTRIBUTION TO THE RELATION BETWEEN PROTEID CLEAVAGE PRODUCTS AND ANAPHYLAXIS.
AB  - Examination of the anaphylactic lung by means of Van Slyke's amino nitrogen
      method gave no evidence of an increased amount of proteid cleavage products of
      any kind in this organ. This investigation gives no support to the hypothesis
      that the true anaphylactic lung of the guinea pig is caused by proteid split
      products.

PMID- 19867698
TI  - FURTHER STUDIES ON THE IDENTITY OF PRECIPITINS AND PROTEIN SENSITIZERS
      (ALBUMINOLYSINS).
AB  - The experiments here recorded, as well as those preceding them and outlined in
      the introductory paragraphs, have had the purpose of analyzing the phenomenon of
      alexin fixation occurring when dissolved, unformed proteins are added to their
      specific antisera. The present experiments have shown that specific precipitates
      have the same relation to the complement fractions first described by Ferrata
      that are possessed by sensitized cells. In this they differ from indifferent
      suspensions, like kaolin, which fix alexin and its fractions indiscriminately,
      fixing the end-piece without dependence upon previous adsorption of the mid
      piece. The writer believes this to be of theoretical importance since it seems to
      show, in the first place, that the fixation of alexin by precipitates is not
      merely a mechanical adsorption, and in that it renders more likely the
      supposition that the so called precipitin is actually a protein sensitizer by
      which a foreign protein is rendered amenable to the proteolytic action of the
      alexin. The visible precipitation in such reactions is merely secondary,
      occurring because of the colloidal nature of the reacting bodies, under
      conditions of quantitative proportions and environment which favor flocculation.
      It does not seem necessary to assume a structure for the so called precipitins
      essentially different from that of other sensitizers. Carried to its logical
      consequences, the acceptance of this view, taking the identity of agglutinins and
      precipitins at least as a possibility, leads to the conception that functionally
      there is but one variety of specific antibodies, and that is the sensitizer which
      makes possible the action of alexin or complement upon various antigens.

PMID- 19867699
TI  - THE TOTAL NON-PROTEIN NITROGEN OF THE BLOOD IN NEPHRITIS AND ALLIED CONDITIONS.
AB  - 1. In a series of non-nephritic individuals the total non-protein nitrogen of the
      blood, determined by Folin's method, was found to lie between 15 and 43
      milligrams per 100 cubic centimeters. From 50 to 60 per cent. of this was in the
      ammonia-urea fraction. 2. In cardiovascular disease with renal congestion, but
      without other renal lesion, there was no evidence of increase of non-protein
      nitrogen in the blood, nor of alteration of the ammonia-urea percentage. 3. In
      chronic nephritis with marked albuminuria and edema there was very little, if
      any, increase or alteration. 4. In chronic nephritis with hypertension the non
      protein nitrogen was definitely increased, ranging from 40 to 180 milligrams per
      100 cubic centimeters of blood. The percentage of the ammonia-urea fraction was
      usually higher than in non-nephritic cases. 5. Cases showing high non-protein
      nitrogen values were subject to rapid fluctuations in these values in the course
      of a few days. As a rule, clinical improvement was associated with a fall of the
      non-protein nitrogen figures to nearer the normal range. 6. Uremia was almost
      always accompanied by an increase of non-protein nitrogen in the blood, but no
      constant relation could be established between the degree of increase and the
      tendency to uremia. 7. Our cases have not yet been followed for a long enough
      period to admit of conclusions as to the possible relation between the degree of
      non-protein nitrogen retention and ultimate prognosis. 8. We believe this method
      to be a valuable aid in the clinical study of nephritis and that it can be
      readily carried out in any well equipped clinical laboratory.

PMID- 19867700
TI  - A STUDY OF THE CEREBROSPINAL FLUID IN ACUTE POLIOMYELITIS.
AB  - The spinal fluid in the cases of acute epidemic poliomyelitis examined was
      usually clear, colorless, and did not appear to be under any great increase of
      pressure. It showed changes in the number of cells present, or in the globulin
      content, or in both, in the majority of cases examined on the first few days
      after onset of symptoms. The number of cells was usually highest during the first
      week, and in one case reached the figure of 1,221 per cubic millimeter. The
      globulin reaction was usually most marked during the third week. The number of
      cells diminished rapidly and was above normal in only 32 per cent. of the cases
      in the third week. The increase in the globulin reaction persisted to the fourth
      week and might be present for a considerably longer period. The cell increase was
      due almost invariably to mononuclear cells of various types. The lymphocytic type
      of cell was the most common. A high polymorphonuclear count was noted in the very
      early stages. All the fluids reduced Fehling's solution. The examination of the
      spinal fluid may be of value in diagnosis in the preparalytic stages and in
      abortive cases. It is not of value in prognosis as to life or ultimate recovery.

PMID- 19867701
TI  - THE CULTIVATION OF AMOEBAE IN PURE CULTURE UPON AUTOLYZED TISSUES.
AB  - Since the purpose of this paper is to record the cultivation of amoebae upon
      autolyzed tissue without bacterial association, the morphological
      characteristics, life cycle, means of differentiating species, and pathogenicity
      of the protozoa have been omitted. These subjects will be considered in later
      publications. The result of this study proves that some species of amoebae from
      liver abscesses and the human intestine can be cultivated upon various autolyzed
      tissues of man and some of the lower animals without a symbiotic microorganism.
      Their cultivation from liver abscesses upon such bacteria-free autolyzed tissue
      indicates that their multiplication in these lesions depends upon some product or
      products in the process of dissociation of the liver cells. That such a process
      exists in amoebic liver abscesses cannot be questioned when histological and
      biochemical studies are made of such lesions, and this explains not only why the
      multiplication of the parasites in the organ occurs, but suggests the probable
      origin of the lesion. It has long been known that tissue kept for several days in
      a perfectly aseptic condition and at body heat, or preferably at slightly higher
      temperature undergoes softening and final disintegration of its cells. Wells and
      others who have made a thorough study of this phenomenon find that different
      enzymic actions take place in this process: thus in the liver they find that
      soluble nitrogen compounds are greatly increased, the nucleoproteids are altered
      by nuclease, the purin bases are freed and in their turn acted upon by the
      guanase and adenase, the fats are split and fatty acids set free, the glycogen
      gives rise to glucose and undergoes further splitting. lecithin is cleaved, and
      allied bodies appear, and there is a marked appearance of cholin and cholesterin.
      Similar changes varying only in degree occur in the process of autolysis of other
      tissues. Furthermore, Duval in his experiments upon the cultivation of Bacillus
      leprae found that the initial multiplication was accomplished when the specific
      organism was in symbiosis with an associated bacterium capable of hydrolyzing the
      leprous tissue. In later experiments he noted that the products of split proteins
      supply what is actually required for the growth of this particular obligate cell
      parasite, and that while this end is reached with bacteria through their
      proteolytic action equally good results can be obtained with tissue free from
      contaminating microorganisms provided that it is allowed to autolyze. The
      separation of amoebae cultivated from the human intestine from their bacterial
      symbiont, and their development upon various autolyzed tissues indicate that it
      is not the bacterium that is essential for the life of these protozoa, but the
      action of the living bacteria upon the protein contained in the media. This would
      explain the failure of many investigators to cultivate amoebae with dead bacteria
      or bacterial filtrates. Mention has been made that the autolyzed tissue used in
      the cultivation experiments gave a distinct acid reaction. The multiplication of
      amoebae upon a medium with such a reaction appears contradictory to the findings
      of Musgrave and Clegg, Walker, and others, who have emphasized the necessity of
      an alkaline medium for the successful cultivation of amoebae with a bacterial
      symbiont, though in accord with what is known to be the reaction of the contents
      from amoebic liver abscesses and of the bloody stools in intestinal amoebiosis.
      The fact should not be lost sight of that, in the cultivation of amoebae, these
      authors lay stress upon the selectiveness of amoebae for a special microorganism.
      A comparison of their work with our own results indicates that bacteria known to
      possess strong hydrolyzing properties, e. g., Vibrio cholerae, Bacillus coli,
      Bacillus subtilis, Vibrio proteus (Finkler-Prior), etc., furnish the best
      symbionts to the amoebae. It is well known that these bacteria growing upon
      gelatin or blood serum liquify the medium and alter its reaction to a marked
      degree of acidity. This acidity, for the most part, results from dissociation of
      the protein molecule contained in the media, for Wiener has shown that autolysis
      does not begin until the normal alkalinity of the tissues has been neutralized by
      the production of organic acids. Since experiments show that the development of
      the amoebae is scant or completely arrested if the autolyzed tissue is smeared
      upon an acid agar base or upon agar with an alkalinity higher than 1 per cent.,
      the limit within which multiplication can occur must be small. It is possible
      that this explains why amoebae are so few in the center of liver abscesses where
      the acidity is very high and so plentiful in or near its walls where the normal
      tissue juices furnish a controlling influence over the acidity of the autolyzing
      tissue. It explains also why a neutral or a 1 to 1.5 per cent. alkaline medium is
      essential for the cultivation of amoebae with a bacterial symbiont. Here the
      necessity for a medium with an alkaline reaction seems necessary, as bacteria,
      especially those having high hydrolyzing properties, develop a marked acidity in
      the medium. If the medium possesses an initial acidity the limit is either
      quickly reached or already present and no multiplication occurs. On the other
      hand, a medium with a reaction too alkaline either inhibits the growth of
      symbiotic microorganisms, or neutralizes the acid products as rapidly as they are
      formed by the associated bacterium. Whether the amoebae cultivated from liver
      abscesses and from the intestinal canal upon diverse autolyzed tissues are able
      to produce lesions similar to those from which they were isolated, or whether
      they are non-pathogenic species which are accidental contaminators to those
      responsible for frank lesions, remains still to be determined. Experiments
      bearing upon these points, as well as on many others made possible by this work,
      are now under way.

PMID- 19867702
TI  - ON THE EXCRETION OF GLYCURONIC ACID IN PNEUMOCOCCUS INFECTIONS, WITH SPECIAL
      REFERENCE TO LOBAR PNEUMONIA.
AB  - 1. It has been found that the amount of glycuronic acid excreted in the urine,
      estimated by Tollens's furfurol distillation method, is increased during the
      febrile period of almost all cases of lobar pneumonia in man. Patients weighing
      from fifty-five to seventy kilograms excrete during the febrile period 0.8 to 1.3
      grams of glycuronic acid in twenty-four hours, while the output of a normal
      individual of the same weight, age, and under similar conditions would not exceed
      0.4 to 0.6 of a gram. 2. This increased output is not dependent on outside
      factors; it is attributable to pathological changes of the organism itself during
      the disease. 3. Similar observations have been made in postpneumonic empyema and
      bronchopneumonia. 4. Fasting rabbits, with general pneumococcus infection, have
      also shown a marked increase in the output of glycuronic acid during the
      pathological process. Whether the conjugated substances with the glycuronic acid
      in the cases studied have the same origin and are qualitatively the same as under
      normal conditions, or whether we are dealing with different compounds, has not
      yet been determined.

PMID- 19867703
TI  - THE HISTOGENESIS OF BLOOD PLATELETS.
AB  - 1. Under normal circumstances blood platelets are largely derived from the
      megakaryocyte of the blood-forming organs. 2. The transitional leucocyte,
      representing a persistent form of the embryonic premegakaryocyte, is a
      circulating homologue of the megakaryocyte and probably plays some part in normal
      platelet formation. 3. Under conditions of excessive demand for platelet
      production, there may be a greater or less reversion to an embryonic mode of
      platelet formation in which less highly specialized cells than the megakaryocyte
      participate in platelet production. 4. In addition to the megakaryocyte, the
      cells that have been observed to take part in platelet formation are hyperplastic
      endothelial cells in the marrow, and mononuclear and transitional cells
      (premegakaryocytes) in the marrow, spleen, and blood.

PMID- 19867704
TI  - CONTRIBUTIONS TO THE STUDY OF THE MECHANISM OF THE GROWTH OF CONNECTIVE TISSUE.
AB  - When connective tissue cells have been cultivated for a certain length of time in
      a medium which has been repeatedly changed, a definite relation arises between
      the rate of growth of the cells and the composition of the medium. It is
      possible, by adding to the culture medium a given quantity of certain substances,
      such as embryonic juices, to foresee the extent to which a fragment of tissue
      composed of a given strain of cells will increase in a given time. The rate of
      growth of a strain of cells can be accelerated or retarded by the addition to the
      medium of activating or retarding substances. The dynamic condition of a strain
      of connective tissue cells, which have been living in a given medium for some
      time, is not a definitely acquired characteristic, but a temporary state, and is
      the product or function of the medium in which the cells are living, and is
      readily modified merely by altering the composition of the medium. A knowledge of
      the characteristics of the growth of connective tissue described has led to a new
      result,-the indefinite proliferation of a strain of connective tissue cells
      outside of the organism. The strain of connective tissue originally obtained from
      a fragment of chick embryo heart, which had been pulsating in vitro for 104 days,
      was still actively alive after sixteen months of independent life and more than
      190 passages. The rate of proliferation of the connective tissue sixteen months
      old equalled and even exceeded that of fresh connective tissue taken from an
      eight day old embryo. It appears, therefore, that time has no effect on the
      tissues isolated from the organism and preserved by means of the technique
      described above. During the sixteenth month of life in vitro the cells increased
      rapidly in number and were able in a short time to produce a large quantity of
      new tissue. This fact, therefore, definitely demonstrates that the tissues were
      not in a state of survival, as was the case in certain earlier experiments, but
      in a condition of real life, since the cells of which they were composed, like
      microorganisms, multiplied indefinitely in the culture medium.

PMID- 19867705
TI  - THE INFLUENCE OF TEMPERATURE ON THE ACTION OF STRYCHNIN IN FROGS.
AB  - In order to establish the influence of temperature upon the effect of varying
      doses of strychnin injected into frogs, the animals must be kept under
      observation for several days and at various definite degrees of temperature.
      Statements that the animal was kept "cold," "at room temperature," or "warm" are
      insufficient. With a certain dose tetanus may result constantly at 30 degrees C.
      yet never appear at 21 degrees C., and either of these temperatures might be
      described as warm, when compared to a room temperature of 15 degrees C.
      Furthermore an animal may apparently fail to respond in the cold to an injection
      of certain doses of strychnin and yet be found in tetanic convulsions the next
      day. That an animal may have late, long lasting, or strong tetanus while kept at
      such a low temperature as 5 degrees C. after an injection of a dose of strychnin
      smaller than 0.01 of a milligram per frog emphasizes the fact that great caution
      must be exercised in formulating laws as to the influence of temperature on drug
      action. The main results of this investigation may be summarized as follows:
      Doses of strychnin amounting to 0.0006 of a milligram per gram of frog will cause
      tetanus at all temperatures between 5 degrees C. and 30 degrees C., although at
      low temperatures the tetanus may appear late. A dose of 0.0003 of a milligram per
      gram of frog will frequently produce tetanus at 5 degrees C. as well as at 30
      degrees or 27 degrees C., but may nevertheless fail to produce any reaction at
      such an intermediary temperature as 21 degrees C. Smaller doses, 0.0002 of a
      milligram per gram, will cause tetanus in the cold but not at high temperatures.
      It may be stated in general that in frogs kept at low temperatures the tetanic
      state sets in later, continues longer, and each tetanic attack is of longer
      duration, while in the interval between the attacks the state of tonus is higher
      and the animals are more irritable than when they are kept at higher
      temperatures.

PMID- 19867706
TI  - ON ELIMINATION THROUGH THE MUCOSA OF THE URINARY BLADDER.

PMID- 19867707
TI  - CONTRIBUTION TO THE CULTIVATION OF THE PARASITE OF RABIES.

PMID- 19867708
TI  - A NOTE ON THE FATE OF TARTRATES IN THE BODY.
AB  - Under the experimental conditions outlined, sodium tartrate subcutaneously
      introduced into rabbits fails to reappear in the urine. It is concluded that the
      disintegrative influence of the salt upon the convoluted tubules is sufficient to
      account for the failure of the salt to be eliminated. No evidence of a vicarious
      function on the part of the glomerulus was observed.

PMID- 19867709
TI  - TARTRATE NEPHRITIS, WITH ESPECIAL REFERENCE TO SOME OF THE CONDITIONS UNDER WHICH
      IT MAY BE PRODUCED.
AB  - Salts of tartaric acid administered subcutaneously to fasting phlorhizinized
      animals exert a markedly detrimental influence upon the secretory efficiency of
      the kidney, which is indicated by a greatly lessened output of certain typical
      urinary constituents. A histological study of the nephritic kidney demonstrates
      that the salts act specifically upon the epithelium of the convoluted tubules,
      and to a less extent upon the tubules of the loops of Henle, the glomerules, and
      interstitial tissue remaining unharmed. In the disintegrative process taking
      place, vacuolation first occurs, is rapidly followed by necrosis, and finally the
      dead cells or their debris may entirely fill the lumina of the tubules and form
      granular and hyaline casts. There is no strict relation between the dose of
      tartrate and the extent of damage inflicted. While large doses invariably induce
      a well marked response small doses may at times produce effects equally
      significant. Tartrates introduced into fasting animals call forth symptoms
      practically identical with those observed in fasting phlorhinized animals. It is
      therefore apparent that in the establishment of the pathological condition under
      discussion phlorhizin is without significant influence. Neither the liver nor the
      adrenal exhibits any detrimental effect from the injection of tartrates. The
      introduction of tartrates by way of the mouth to fasting rabbits is not nearly so
      effective in the production of nephritic symptoms as the administration of much
      smaller doses subcutaneously. In general, under the former circumstances the
      initial stages only of epithelial disintegration of the convoluted tubules
      obtain, which, however, are scarcely sufficient to account for the rapidity with
      which death usually ensues. Although in well fed animals distinct pathological
      changes in the kidney are induced by the introduction of tartrates per os, these
      abnormalities are less in degree, but similar in kind, than those provoked under
      like conditions in the fasting animal. When tartrates are given subcutaneously to
      well fed rabbits the effects evoked are somewhat less pronounced than when the
      salts are injected into fasting animals. From these facts it is evident that the
      state of nutrition plays a part in the development of tartrate nephritis. It is
      indicated that the introduction of a sufficiency of alkali to animals in a state
      of fasting permits a greater elimination of urinary constituents during tartrate
      nephritis than obtains under similar circumstances when the alkali is omitted.
      Histologically there is evidence that the administration of alkali exerts a
      slight modifying action.

PMID- 19867710
TI  - A STUDY OF RENAL SECRETION DURING TARTRATE NEPHRITIS.
AB  - After the intravenous introduction of a solution containing sodium chloride and
      urea into the rabbit during pronounced tartrate nephritis, all the chloride
      reappears in the urine within forty-eight hours. On the other hand, the nitrogen
      of the urine remains far below that usually eliminated by the normal animal under
      the experimental conditions; in other words, little or none of the urea injected
      is excreted by the kidney. In the light of the histological findings these
      results are interpreted to mean that under normal conditions chlorides and water
      are passed through the glomerular mechanism, whereas urea becomes a urinary
      constituent by way of the convoluted tubules. These results constitute a direct
      confirmation of the older observations of others concerning the elimination by
      the kidney of the substances under discussion. No evidence was obtained that the
      glomerulus may take over the function of the tubular epithelium.

PMID- 19867711
TI  - STUDIES ON THE CIRCULATION IN MAN : VII. THE BLOOD FLOW IN THE FEET.
AB  - 1. The blood flow in the feet is smaller per unit of volume of the part than in
      the hand, the ratio of foot flow to hand flow per 100 cubic centimeters of the
      part usually lying in normal persons between 1 to 3 and 1 to 2. 2. In the supine
      position, with the legs hanging down, the flow in the feet seems to be somewhat
      greater than in the sitting position.

PMID- 19867712
TI  - STUDIES ON THE CIRCULATION IN MAN : VIII. THE BLOOD FLOW IN THE FEET WITH SPECIAL
      REFERENCE TO FEVER.
AB  - 1. In the cases of fever investigated the flow in the feet never exceeded the
      normal flow and was usually much below the normal 2. In explanation of the
      relatively small foot flow in the fever cases it is suggested that the
      vasoconstrictor mechanism of the peripheral parts, especially of the skin, is
      abnormally excited, and some direct evidence that this is the case is brought
      forward. 3. The significance of this hypersensitiveness, or at least increased
      action, of the cutaneous vasoconstrictor mechanism is assumed to be that the
      peripheral vasoconstriction is a compensatory arrangement which secures for the
      organs mainly suffering from the infective process an increased flow of blood. 4.
      On this hypothesis the rise of temperature is, chiefly at least, secondary,
      inevitably following the vasoconstriction, provided that the metabolism is, upon
      the whole, not diminished. 5. Accordingly the rational treatment of hyperpyrexia,
      or of pyrexia if it is considered necessary to treat it, is to abstract heat by a
      process which will not diminish and may even increase the cutaneous
      vasoconstriction. This condition is exactly fulfilled by the cold bath, at least
      as regards its initial effect. Other so called tonic effects of the cold bath are
      not considered here. Antipyretic drugs which act by dilating the cutaneous
      vessels would seem to be inferior in this regard. They diminish the temperature,
      it is true, but at the cost of defeating the beneficial redistribution of the
      blood which it is the function of the peripheral vasoconstriction to insure. 6.
      It is obvious that for the elimination of a given quantity of heat from the skin
      by radiation and conduction in fever, a smaller cutaneous blood flow will suffice
      than with normal body temperature, since the elimination of heat per gram of
      blood passing through the surface must be greater in fever owing to the greater
      difference of temperature between the surface of the body and its surroundings. I
      am much indebted to the staff of the City Hospital for their cooperation which
      has rendered this investigation possible.

PMID- 19867713
TI  - A STUDY OF THE BLOOD IN RATS RECOVERED FROM IMPLANTED SARCOMA.

PMID- 19867714
TI  - THE MECHANISMS OF METASTASIS FORMATION IN EXPERIMENTAL CANCER.

PMID- 19867715
TI  - THE INFLUENCE OF TEMPERATURE AND FLUID MEDIUM ON THE SURVIVAL OF EMBRYONIC
      TISSUES IN VITRO.
AB  - 1. Embryonic chick and rat tissues preserved at temperatures ranging from -7
      degrees to +20 degrees C. live longest at about +6 degrees C. The duration of
      life under the most favorable conditions is less than twenty days. 2. The kind of
      isotonic medium used,-plasma serum, Ringer solution, or normal salt solution,
      does not appreciably influence the period of survival. The quantity of medium in
      proportion to tissue is similarly without marked effect.

PMID- 19867716
TI  - REGENERATION OF AXIS CYLINDERS IN VITRO : SECOND COMMUNICATION.
AB  - It has been shown for the first time that nerve fibers grow out from pieces of
      cerebellum of young cats and guinea pigs, when cultivated in coagulated plasma.
      The same phenomenon has been observed in cultures of spinal ganglia. The nerve
      fibers do not anastomose and they extend into the plasma unaccompanied by
      structures of any kind.

PMID- 19867717
TI  - RESISTANCE TO A TUMOR-PRODUCING AGENT AS DISTINCT FROM RESISTANCE TO THE
      IMPLANTED TUMOR CELLS : OBSERVATIONS WITH A SARCOMA OF THE FOWL.
AB  - Ultraviolet light rapidly kills the cells of a transplantable sarcoma of the fowl
      without notably injuring the etiological agent associated therewith. The Roentgen
      ray has little effect on either cells or agent. Fowls manifest two sorts of
      resistance to the avian tumor, one directed against the implanted tumor cells as
      such, the other against the action of the etiological agent to cause a neoplastic
      change. In the individual fowl the two resistances appear to be independent of
      one another, though they may exist together or may both be absent. A recognition
      of them will perhaps explain some features in the biology of other tumors.

PMID- 19867718
TI  - THE EFFECT OF INTRASPINOUS INJECTIONS OF SALVARSAN AND NEOSALVARSAN IN MONKEYS.

PMID- 19867719
TI  - A STUDY OF THE SPIROCHAETICIDAL ACTION OF THE SERUM OF PATIENTS TREATED WITH
      SALVARSAN.
AB  - 1. The serum of rabbits treated intravenously with neosalvarsan, and of
      syphilitic patients treated intravenously with salvarsan or neosalvarsan, has a
      definite spirochaeticidal action upon Spirochoeta duttoni. 2. Although this
      spirochaeticidal action is exerted in vitro, it can be demonstrated only after
      the treated spirochaetae are injected into susceptible animals. 3. A curative
      action of the serum of neosalvarsan-treated rabbits is exercised on mice infected
      with Spirochoeta duttoni. 4. The spirochaeticidal action of the serum of
      salvarsan-treated rabbits and patients is markedly increased by heating at 56
      degrees C. for thirty minutes. 5. The increased spirochaeticidal action produced
      by heating is due in part to the destruction of some inhibitory substance
      contained in normal serum and in part to a direct effect of the heat upon the
      serum and salvarsan mixture. 6. Cerebrospinal fluid does not contain the
      inhibitory substance present in normal unheated serum.

PMID- 19867720
TI  - AN ELECTROCARDIOGRAPHIC STUDY OF THE ANAPHYLACTIC RABBIT.
AB  - Electrocardiographic examination of rabbits during the anaphylactic reaction
      revealed marked and various changes of the heart's activity in twenty-two out of
      twenty-four animals. Changes occurred in fatal as well as in non-fatal cases,
      after the vagi were cut as well as when they were intact. Cardiac disturbances
      are thus a practically constant result of serum anaphylaxis in the rabbit. It
      therefore is possible that anaphylaxis plays a role in the causation of certain
      cardiac derangements in man.

PMID- 19867721
TI  - EXPERIMENTS ON THE CULTIVATION OF THE MICROORGANISM CAUSING EPIDEMIC
      POLIOMYELITIS.

PMID- 19867722
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : VI. THE BLOOD PICTURE AT VARIOUS PERIODS AFTER SPLENECTOMY.
AB  - After splenectomy anemia usually develops quickly and reaches its height in from
      three to six weeks; then with gradual improvement the blood picture approaches
      the normal after about three to four months, with complete return to normal in
      five to ten months. Accompanying this is marked leucocytosis reaching its height
      in twenty-four hours but persisting to a slight degree for several months.
      Variations, however, may occur, in that the anemia may develop slowly and be of
      slight degree, or the reparative process may be delayed and up to ten months
      incomplete. The anemia is, however, inevitable, as is also, later, some degree of
      repair.

PMID- 19867723
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : VII. THE EFFECT OF HEMOLYTIC SERUM IN SPLENECTOMIZED DOGS.
AB  - The increased resistance of the red blood corpuscles characteristic of the
      splenectomized animal is as evident one year after removal of the spleen as it is
      at earlier periods. So also is the decreased tendency to jaundice after the
      administration of hemolytic serum. The increase in resistance of the red cells
      cannot be explained on the basis of an increase in reticulated cells in the
      circulating blood.

PMID- 19867724
TI  - A STUDY OF THE RELATION OF PULMONARY AND BRONCHIAL CIRCULATION.
AB  - The most striking point brought out in this study is that as long as a definite
      pressure is maintained in either the pulmonary or bronchial circulations, the
      admixture of bloods is extremely limited. It is easily conceivable that more
      mixture occurs normally than under the conditions of the experiment, but there is
      no reason for considering this to be a large difference. If, however, in either
      system the pressure sinks to zero the possibility of supply by the other system
      becomes evident. It takes much longer for the mass injected through the bronchial
      arteries to penetrate to all parts of the lung than when the mass is injected
      through the pulmonary artery; but when accomplished, the injection reaches to all
      capillaries including those of the pleura, the only vessels remaining uninjected
      being the larger trunks of the pulmonary artery. On the other hand, the injection
      of the bronchial vessels by way of the pulmonary arteries is not complete with
      normal pressure, but occurs rapidly when a high pulmonary pressure is employed.
      It is therefore probable that either circulation can suffice for the simple
      nutritive demands of the lung if the other system is interfered with. It has been
      shown that embolism of the pulmonary artery, without other circulatory
      disturbance, does not lead to necrosis of the affected area of the lung, but it
      is probable that the preservation of circulation is not due to collateral
      bronchial circulation so much as to the free anastomosis and early division into
      capillaries of the pulmonary artery. In support of this statement is the fact
      that the appearance is not altered when the bronchials are ligated at their
      origin. The same ligation shows no subsequent interference with the nutrition of
      the bronchi up to a period of five weeks, demonstrating that the pulmonary
      circulation is sufficient to provide for the nutrition of the bronchi. If,
      however, as Virchow has shown, the pulmonary artery supplying an entire lobe be
      occluded, the bronchial circulation can and does suffice for the nutrition of the
      lobe. In the case of the occlusion of a branch of the pulmonary artery the
      pressure in the area interfered with does not sink to zero because of the
      collateral circulation in this area; whereas, if the main trunk is occluded no
      collateral supply is available, the pressure sinks to zero, and the bronchial
      artery becomes available as a source of blood supply. It must be remembered that
      the lung tissue, as a whole, has ready access to oxygen and this gas is the
      nutritive element acquired by the blood in the lungs. From these studies it would
      appear that the part of the lung tissue not in intimate contact with oxygen in
      the air is supplied by oxygenated blood of the bronchial arteries, and that the
      tissues through which the pulmonary blood circulates take up whatever organized
      nutriment they need from the pulmonary blood and possibly provide for their
      oxygen and carbon dioxide interchange (which must be very slight) either directly
      with the alveolar air, or by finding sufficient oxygen in the venous blood of the
      pulmonary artery. The studies of the injected specimens confirm Kuttner's
      findings of a very rapid breaking up of the pulmonary artery into capillaries. In
      all the specimens studied it was found that although the pleural vessels can be
      injected by way of the bronchial arteries when there is zero pressure in the
      pulmonary arteries, yet when the two sets of vessels are injected simultaneously
      in the dog, the pleural vessels invariably derive their supply of injection mass
      from the pulmonary artery.

PMID- 19867725
TI  - STUDIES IN INFARCTION : III. THE CIRCULATION IN EXPERIMENTAL PULMONARY EMBOLISM.
AB  - From series 1 it is concluded that increases in pulmonary pressure improve the
      circulation in the embolic areas and that decreases in pulmonary pressure limit
      the circulation in the same areas. In this series the bronchial vessels showed no
      tendency to take up the circulation in the area of pulmonary embolism until the
      pulmonary pressure was as low as zero, and then only to a limited degree. It has
      been shown, however, that in the circulation of an entire lobe the fall to zero
      pressure in the pulmonary circuit is followed by almost complete taking over of
      the circulation by the bronchial arterial supply and the most reasonable
      explanation of why this does not occur when embolism is present in a smaller
      branch of the pulmonary is the inference that the physiological anastomosis
      between the two systems takes place in part before the pulmonary artery breaks up
      into branches small enough to be occluded by seeds of about three millimeters in
      diameter. From series 2 it is concluded that although increases in pressure in
      the bronchial arteries cause somewhat greater inflow of bronchial injection mass
      into the embolic area, extremely high pressures are not sufficient to provide for
      complete circulation in the same district. This fact would tend to support
      further the belief that the anastomosis between the two vascular systems occurs
      before the smaller divisions of the pulmonary artery are reached. From series 3
      it is concluded that with a zero pressure in the pulmonary artery there is
      improved injection of the embolic area through the bronchial artery which is to
      be expected when it is remembered that zero pressure in the pulmonary artery
      favors a taking over of the circulation by the bronchial system. What pressure is
      found in the smaller pulmonary vessels is supplied by the bronchials. It has been
      shown that the anastomosis between the two systems probably occurs before the
      branches are reached which would provide lodgment for the turnip radish seeds.
      The pressure supplied by the bronchials would naturally be less beyond this point
      and hence the injection would be less complete in the embolic area than in the
      normal lung. This is shown to be the case by the results of the experiment. From
      series 4 it is concluded that the absence of pressure in the bronchial
      circulation favors a better injection of the embolic area through the pulmonary
      vessels, which is to be expected when it is recalled that not until zero pressure
      is reached in the bronchial circuit does the pulmonary artery supply the
      bronchial vessels with blood. Throughout the study it was found that whenever the
      two vascular systems were injected simultaneously the pleural vessels over the
      embolic area, as well as those over the normal lung, received their supply from
      the pulmonary vessels. When only one system was used for injection the pleural
      vessels over the embolic area showed about the same degree of injection as those
      of the embolic area itself.

PMID- 19867726
TI  - THE PURINES AND PURINE METABOLISM OF SOME TUMORS IN DOMESTIC ANIMALS.
AB  - The purines of tumors are generally the same as those of the normal tissue,
      chiefly guanine and adenine, little more than traces of xanthine, and relatively
      small amounts of hypoxanthine being found. No uric acid was found in the tumors
      of this series. In one tumor, an embryonal adenosarcoma in a pig's kidney, a
      large amount of hypoxanthine, and no adenine was found, while the yield of
      xanthine was also unusually high. This result cannot be explained at present on
      experimental grounds, but evidently a nucleic acid complex containing no adenine
      was encountered. Possibly hypoxanthine was present in inosinic acid. The purine
      enzymes are generally the same in tumors as in the normal tissue from which the
      tumors are derived. This fact sometimes makes it possible to learn by chemical
      study from what tissue a given kind of tumor is derived, when the microscopic
      evidence is inconclusive. Although the liver of the sheep contains the enzyme
      xanthine oxidase, it may be absent from primary tumors in the sheep liver, as it
      has also been shown to be from secondary tumors in the human liver. As xanthine
      oxidase is one of the last of the purine enzymes to develop in the embryonal
      organism, its absence in a malignant tumor containing otherwise the same purine
      enzymes as the tissue from which it is derived, is evidence of the embryonal
      character of the tumor tissue.

PMID- 19867727
TI  - ON THE HEMOLYTIC PROPERTIES OF FATTY ACIDS AND THEIR RELATION TO THE CAUSATION OF
      TOXIC HEMOLYSIS AND PERNICIOUS ANEMIA.
AB  - 1. The smallest amount of the sodium soaps necessary for the complete hemolysis
      of 0.5 of a cubic centimeter of a 5 per cent. suspension of the red blood
      corpuscles of the sheep, ox, rabbit, dog, or of man, is about the same,-0.03 of a
      milligram in the case of the following acids: oleic, linoleic, dibromostearic,
      chloriodostearic, and two isomeric monobromostearic acids; in the case of erucic
      acid about twice as much of the soap was found to be necessary; in that of
      palmitic or of dihydroxystearic acid more than ten times as much. 2. The minimum
      hemolytic quantity of the sodium soaps of the highly unsaturated acids obtained
      from cod liver oil and from linseed oil is only very slightly less than that of
      sodium oleate. 3. It follows, therefore, from these results that hemolysis by
      unsaturated fatty acids is not more active in proportion to the degree to which
      these acids are unsaturated, nor is it diminished when the unsaturated carbon
      atoms are saturated by halogens. It is, on the other hand, greatly diminished
      when they are converted into the corresponding hydroxyl acids, which are
      hemolytic only to the same degree as the saturated acids. 4. The idea that toxic
      hemolysis, in disease, in poisoning by phosphorus or toluylene diamine, results
      from the liberation of specially hemolytic fatty acids from the fatty complexes
      of disintegrating cells is not well supported by evidence; none of the fatty
      acids, still less any of the fatty complexes from which these acids can be
      obtained in any of the organs examined, either in this work or in the work of
      others that has preceded it, show on analysis any evidence for the existence of
      fatty acids more toxic than the common oleic acid which is constantly being set
      free by hydrolysis from common fat in health.

PMID- 19867728
TI  - PNEUMONIC LESIONS CAUSED BY BACILLUS MEGATHERIUM.
AB  - THE ESSENTIAL POINTS OF OUR RESULTS ARE AS FOLLOWS: The saprophytic Bacillus
      megatherium produced a definite pulmonary lesion which in gross appearance
      resembled the lesion of lobar pneumonia. The lesion was one of intense leucocytic
      exudation which, as in some other cases of experimental lobar pneumonia, did not
      invade the framework of the lung. But the exudate contained no fibrin. There were
      practically no bacilli, either in the heart's blood or in the lung. The growth of
      two colonies from one of the cases hardly changes the rule. The lesion did not
      progress after twenty-four hours; nor did it show a definite increase in extent
      or intensity with the increase in quantity of the injected cultures. The
      resolution of the exudate began practically at the end of twenty-four hours and
      was far advanced on the third day. Although there was considerable leucocytic
      infiltration there was no phagocytosis apparent twenty-four hours after
      inoculation. Taking all the facts into consideration one gains the impression
      that the lesion produced by the saprophytic Bacillus megatherium differs only
      quantitatively from that produced by an avirulent pneumococcus. The fact stands
      out prominently that a saprophytic bacterium is capable of producing a pneumonic
      lesion similar in gross appearance to that of mild lobar pneumonia. It is not
      improbable that other saprophytes may be capable of producing pneumonic lesions
      which, in specific instances, may resemble lobular pneumonia.

PMID- 19867729
TI  - THE CHARACTER OF THE PNEUMONIC LESIONS PRODUCED BY INTRABRONCHIAL INSUFFLATION OF
      VIRULENT STREPTOCOCCI.
AB  - Comparing the pneumonic lesions produced by this very virulent streptococcus with
      those caused by a mildly virulent strain of the same organism, we find that with
      one exception the differences between them are only of a quantitative nature and
      not striking. There are the same intense leucocytic exudation into the alveoli
      and the leucocytic infiltration of the framework of the lungs. Macroscopically
      the pneumonia produced by the virulent organism was, as a rule, lobular in
      character. Occasionally, however, especially when large doses of the culture had
      been given, the gross appearance of the lesion gave the impression of a lobar
      pneumonia. But even in these cases the cut surface showed that the solid areas
      were separated by softer and lighter areas of aerated, congested, or edematous
      lung substance. Pleurisy was practically absent from the lungs in this series of
      experiments; only one case showed a narrow strip of fibrinous exudate on the
      pleura. Although in some instances large doses of the cultures were given and
      some dogs were permitted to live six or seven days, there was no mortality among
      the dogs in these experiments, just as there had been none among the animals
      experimented upon with the streptococcus of very low virulence. The course of the
      pneumonia caused by the virulent organism seemed to be somewhat longer than that
      produced by the less virulent one; areas of resolving pneumonia were found to
      persist on the sixth and seventh days after the injection, and in one such
      instance the solid focus contained viable organisms. There was some difference in
      the amount of fibrin present in the exudate caused by the two strains of
      streptococci. Although even in these experiments the amount of fibrin present was
      less than that found in the lesion produced by the virulent pneumococcus, it was
      perceptibly larger than the very small amount found in the lesions caused by the
      less virulent strain of streptococcus. It should be mentioned that there was no
      difference in the degree of phagocytosis observed in these two series of
      experiments. It was not marked in either case. One point of difference in the two
      series was noted: during the first forty-eight hours after insufflation of the
      virulent strain of streptococcus the blood of the animals obtained from the
      jugular vein during life and from the heart after death contained living
      organisms, while in the experiments with the slightly virulent streptococcus no
      living cocci were recovered from the blood. The virulence of the strain of
      streptococcus employed in the present investigation was, as has been pointed out,
      similar to that of the pneumococcus employed in the investigation of Lamar and
      Meltzer and in many of our own experiments, as far as mice were concerned, since
      both killed mice weighing fifteen grams in doses of 0.000,001 of a cubic
      centimeter in twenty-four to thirty-six hours. The findings in the lesions caused
      by these two organisms are comparable and therefore some deductions may be drawn
      regarding the similarity or dissimilarity of their actions. One of the first
      things we wish to bring out is the correction of our former statement regarding
      the presence of the cocci in the blood. As our new investigation shows, there is
      evidently no difference in this respect between the streptococcus and the
      pneumococcus. When both organisms are highly virulent they can be found in the
      circulating blood of the living dog or in the heart's blood of the dead dog
      during the first twenty-four or forty-eight hours after an intrabronchial
      insufflation. On the other hand, the present investigation rather confirms in a
      general way our first contention that the pneumonic lesions produced by the two
      different organisms differ distinctly in many ways. There is the difference in
      the mortality; even with fairly large quantities of the culture of the virulent
      streptococcus the mortality was nil in this series, although some of the dogs
      were kept alive for six and seven days. The mortality of the pneumococcus
      infection depends upon the quantity insufflated and may amount, as Lamar and
      Meltzer pointed out, to 16 per cent. The gross appearance of the lesion produced
      by the pneumococcus is, as frequently stated, that of a lobar pneumonia,
      frequently accompanied by a fibrinous exudate on the pleura. The gross appearance
      of the lesion produced even by a virulent streptococcus is, as a rule, that of a
      lobular pneumonia and is practically never accompanied by pleurisy. In the few
      instances in which large quantities of the streptococcus were given and the
      outward appearance of the lungs approached that of a lobar pneumonia, it was
      found that on section of the consolidated lung the solid foci proved to be
      separated by lighter areas of aerated, congested lung. In the lesions produced by
      the virulent streptococci the walls of the finer bronchi and the framework of the
      lung were markedly infiltrated with leucocytes, while in the lobar pneumonia
      produced by the pneumococcus the framework remained free from such infiltration.
      Finally there is the unmistakable difference in the amount of fibrin present in
      the alveolar exudate. While in the exudate of the lesion produced by the virulent
      streptococcus the amount was perceptibly larger than the insignificant amount
      present in the lesion caused by a slightly virulent strain, it is not to be
      compared with the large amount of fibrin which exists in the exudate of
      pneumococcus pneumonia. The several investigations which we have carried out seem
      to show conclusively that in general the streptococcus causes a lobular pneumonia
      which, besides the leucocytic intra-alveolar exudation, is characterized by a
      leucocytic infiltration of the lung framework, and that the pneumococcus causes a
      lobar pneumonia, which is practically free from leucocytic infiltration of the
      interstitial tissue of the lung. Furthermore, a virulent pneumococcus causes a
      lesion in which fibrin is a prominent element in the exudate and that element
      distinguishes the exudate sharply from the exudate of the lesion caused by a
      virulent streptococcus in which fibrin is present only in moderate amount. It
      distinguishes it in a still more striking manner from the exudates of the lesions
      caused by non-virulent pneumococci or streptococci, in which fibrin is present
      only in very small amounts. It seems that the formation of fibrin is connected in
      some specific way with the pneumococcus on the one hand, and with the virulence
      of the organism on the other. For even with the relatively small amounts of
      fibrin present in the exudates of lesions caused by the streptococcus there is a
      perceptible difference in the quantity according to the virulence of the
      organism. Whether fibrin is a means which enhances virulence, or whether it is a
      reaction product against it, our experiments so far do not entitle us to discuss.

PMID- 19867730
TI  - DISTURBANCES OF THE HEART-BEAT IN THE DOG CAUSED BY SERUM ANAPHYLAXIS.
AB  - Anaphylactic shock in the dog, caused by the intravenous injection of horse serum
      into sensitized animals, may produce definite cardiac disturbances which are
      revealed by the electrocardiogram. These cardiac changes consist of disturbances
      in conduction of the heart impulses, abnormalities in the ventricular
      contractions, and other unusual disturbances of the mechanism of the heart-beat.
      They come on very quickly after the injection of serum and may be of short
      duration, and are not obtained during anti-anaphylaxis. They are not the result
      of the marked fall in blood pressure which occurs, nor does the central cardiac
      inhibitory mechanism play a part in their production. These cardiac disturbances
      apparently are a definite primary expression of anaphylactic shock in the dog.
      The right ventricle seems to be more affected than the left.

PMID- 19867731
TI  - EXPERIMENTS ON THE CULTIVATION OF SO CALLED TRACHOMA BODIES.
AB  - 1. An organism was isolated and studied in pure cultures from cases of
      conjunctivitis accompanied by the so called trachoma body inclusions, as well as
      from a case of old trachoma without inclusions. 2. This organism was not found in
      the cultures made from other forms of conjunctivitis in which the inclusions were
      absent. 3. The organism presents the morphological features characteristic of so
      called trachoma bodies. It undergoes an early transformation, during which the
      forms known as initial bodies appear, and a later change, during which forms
      resembling elementary granules arise, while certain intermediate forms between
      these occur simultaneously. 4. No definite cell inclusions could be produced in
      monkeys by inoculating pure cultures of the organism. 5. The cultivation of this
      organism from a case of trachoma without the cell inclusions, together with the
      previously ascertained fact that the inclusions can be produced in suitable
      animals by inoculating such material directly from a human case, suggests the
      possibility of the organism being still present in such cases of trachoma,
      although not in the form of cell inclusions. 6. The facts presented justify the
      statement that by a suitable method an organism resembling the various important
      stages of the trachoma bodies and totally distinct from the gonococcus has been
      obtained in a living condition, capable of indefinite cultivation from cases of
      human trachoma and inclusion conjunctivitis. Whether the organism and trachoma
      bodies are identical cannot be positively stated at present. But the way is now
      opened to determine this point, as well as the specificity of the trachoma
      bodies.

PMID- 19867732
TI  - THE TOXICITY OF GENTIAN VIOLET AND ITS FATE IN THE ANIMAL BODY.

PMID- 19867733
TI  - THE COMPARATIVE VIABILITY OF PNEUMOCOCCI ON SOLID AND ON FLUID CULTURE MEDIA.
AB  - 1. Pneumococci, when freshly isolated from the body, are able to live and
      multiply when a small number of them are inoculated into a small amount of broth.
      If, however, the inoculations are made in large amounts of broth, many more
      bacteria must be inoculated in order that they may grow. 2. It requires much
      smaller numbers of pneumococci to start a growth on agar than are required to
      start a growth in broth. 3. This predilection for solid medium disappears when
      the bacteria are grown for some time outside the body. 4. This phenomenon is not
      dependent on differences in chemical composition between the two media employed
      or on the presence of more available oxygen in one case than in the other. 5. It
      is probably dependent entirely on physical differences in the two kinds of media,
      and bears some relation to the differences in possibilities for diffusion in the
      two media.

PMID- 19867734
TI  - STUDIES ON FERMENT ACTION : VIII. THE TOXICITY OF SOME PROTEOSES.

PMID- 19867735
TI  - STUDIES ON FERMENT ACTION : IX. A NOTE ON THE RELATION BETWEEN LYSIS AND
      PROTEOLYSIS OF PNEUMOCOCCI.
AB  - Burgers, Schermann, and Schreiber (1) studied "Auflosungserscheinungen von
      Bakterien," and concluded that ferments were probably not the main factor in such
      lysis. Kantorowicz (2) in studying antiferment and bacteriolysis came to the
      opinion that there was an antiferment in the bodies of bacteria which prevented
      digestion. This antiferment was likewise an antibody to serum bacteriolysins. But
      Kantorowicz used as a standard of ferment action merely the clearing up of the
      bacterial suspension. Our report shows that lysis of pneumococci may be
      independent of ferment action, and that it is not correct to assume that clearing
      up of a bacterial suspension even in the presence of a proteolytic ferment
      indicates proteolysis.

PMID- 19867736
TI  - INTRAPERITONEAL LYSIS OF TUBERCLE BACILLI.
AB  - 1. Tubercle bacilli injected into the peritoneal cavities of tuberculous guinea
      pigs, rats, rabbits, dogs, and monkeys, rapidly disappear from the peritoneal
      fluids, while persisting in the peritoneal fluids of normal control animals. 2.
      This disappearance is in part due to an adhesion of the injected bacilli to the
      peritoneal leucocytes and a fixation of the leucocytes on the omentum. 3. The
      injected tubercle bacilli can be recovered quantitatively from the peritoneal
      cavities of normal guinea pigs from one and one half to two hours after the
      injection, while from tuberculous guinea pigs only 65 per cent. of the bacilli
      can be recovered at this time. 4. Isolated peritoneal tissues from tuberculous
      guinea pigs have the power of destroying tubercle bacilli in vitro. 5. A second
      factor reducing the number of tubercle bacilli free in the peritoneal fluid is
      therefore an actual lysis of the bacilli. 6. The intraperitoneal lysis is not due
      solely to substances present in the circulating fluids, since the phenomenon
      cannot be produced by these fluids in vitro, and since a lytic power cannot be
      passively conferred even by a direct transfusion of blood from tuberculous to
      normal animals. 7. The intraperitoneal lysis is apparently due to specific
      changes in the fixed peritoneal cells of the tuberculous animals.

PMID- 19867737
TI  - FURTHER EXPERIMENTAL STUDIES IN TETANY.
AB  - It has been our aim to determine in what particular the blood is altered during
      tetany so that it can produce hyperexcitability of the motor nerves. As a working
      hypothesis it has been assumed that (1) there may be a lack of calcium in the
      blood and tissues; (2) there may be a circulating poison which like an oxalate
      could render inactive the circulating calcium; and (3) there may be a substance
      in circulation vaguely resembling strychnia in its action upon the nervous system
      and directly causing the hyperexcitability. It is impossible to decide with our
      present knowledge which, if any, of these explanations is the true one, but
      certain experimental results are brought forward. If tetany blood be used to
      perfuse a normal leg the excitability of the nerves rises to a characteristically
      high level and the addition of parathyroid extract to the blood has little or no
      effect in lowering this excitability. Parathyroid extract whether from the ox or
      the dog fails when injected into the circulation of an animal in tetany to reduce
      the excitability of the nerves markedly or permanently, although it seems to
      affect the more sensitive ganglion cells thus cutting off excessive impulses to
      the periphery. Although the nerves remain hyperexcitable, tetany is usually much
      diminished or abolished entirely. This seems to be analogous to the action of
      ether or any other anesthetic which may inhibit the activities of the ganglion
      cells, although it leaves the nerves excitable and able to conduct impulses. An
      animal in tetany relaxes instantly on being given ether although the excitability
      of the nerves to electric currents is little changed. Bleeding followed by the
      replacement of the blood with an indifferent solution free from calcium stops
      tetany and lowers the excitability of the nerves. Probably this cannot be
      ascribed to the removal of a circulating poison, but rather to a general
      disturbance of the nutrition of the nervous system. Oxalate-like substances
      introduced into the circulation rapidly, and for a short time only, may kill the
      animal, but they seem to produce no change in the excitability of the nerves. If
      the solution is injected very slowly and over a long period the protective action
      of the body seems to be overcome and the excitability of the nerves rises to high
      levels. This seems to resemble somewhat the latent period after the destruction
      of the parathyroid before tetany begins. Direct analysis of the blood shows that
      as compared with the normal, the blood of an animal in tetany is very poor in
      calcium. Administration of parathyroid extract does not increase this calcium
      content. On the contrary, if the extirpation of the parathyroids has been
      incomplete so that tetany does not appear, the calcium content of the blood is
      that of the normal animal. Even yet, therefore, in spite of our efforts to shake
      it, the theory that tetany is closely dependent upon a disturbance of the calcium
      content of the blood is supported by stronger evidence than any other idea, but
      much remains to be done before a clear conception of the process is reached.

PMID- 19867738
TI  - THE CHARACTERS OF A THIRD TRANSPLANTABLE CHICKEN TUMOR DUE TO A FILTERABLE CAUSE.
      A SARCOMA OF INTRACANALICULAR PATTERN.
AB  - A spontaneous chicken sarcoma, peculiarly fissured by blood sinuses, and with a
      tendency to intracanalicular extension into them, has been transplanted and
      studied in eight successive groups of fowls. Histologically the growth is a
      characteristic neoplasm, while in its transfer to new hosts a real
      transplantation is obviously involved. The development of the first few series of
      transplantation tumors was very slow. They exhibited the histological structure
      of the original growth and had the same tendency to metastasize to the skeletal
      muscles. Recently the tumor has grown more rapidly and in a higher percentage of
      hosts. With this has come a simplification of structure to that of a pure,
      spindle-celled sarcoma. Fowls of an alien variety (Plymouth Rock) form quite as
      good hosts for the tumor as those of the sort (brown Leghorn) in which it was
      originally found. It has not grown in pigeons, rats, or mice. The question of the
      cause of the tumor is not taken up in the present paper. It has been found to be
      due to an agent which will pass through Berkefeld filters. The growth is quite
      distinct in its characters from the other two transplantable neoplasms of the
      fowl (a spindle-celled sarcoma, an osteochondrosarcoma) which have such a cause.
      No growth like it has been observed among the forty-three spontaneous tumors of
      the fowl that have come under our observation.

PMID- 19867739
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : VIII. REGENERATION OF THE BLOOD OF SPLENECTOMIZED DOGS AFTER THE
      ADMINISTRATION OF HEMOLYTIC AGENTS.
AB  - In the splenectornized dog the anemia caused by hemolytic poisons (hemolytic
      immune serum and sodium oleate) and by bleeding is of a severer grade, runs a
      longer course, and is accompanied by a less rapid regeneration of the blood than
      is the case in the normal dog. Also in the splenectomized dog, especially after
      the use of hemolytic serum, the leucocytosis is greater than in the normal
      animal. The splenectomized dog almost uniformly exhibits an increased resistance
      of the red cells to hypotonic salt solution, but after the administration of
      hemolytic poisons, and especially hemolytic serum, this increased resistance
      disappears and a decreased resistance persists for long periods of time. The same
      change occurs in the normal dog, but in the latter the return to the previous
      degree of resistance is more rapid than in the splenectomized animal.

PMID- 19867740
TI  - THE PRODUCTION OF EXPERIMENTAL NEPHRITIS BY REPEATED PROTEID INTOXICATION.
AB  - The repeated injection of small doses of horse serum and egg-white in dogs, cats,
      rabbits, and guinea pigs that have been sensitized to these proteins, causes
      injury to the cells of various organs and tissues with resulting inflammatory
      reactions. The changes are especially marked after intraperitoneal injections in
      the peritoneum and after intravenous injections in the livers of rabbits and
      cats, and in the myocardium and kidneys of all groups of animals. In dogs and
      rabbits, especially, there develops a well marked nephritis characterized by
      degeneration and necrosis of the epithelium of the loops of Henle, of the
      collecting tubules, and less frequently of the convoluted tubules. This is
      accompanied by an extensive small round cell infiltration of the interstitial
      tissue and later the formation of connective tissue. Together with these changes
      there are acute and chronic alterations in the glomeruli of all groups of
      animals. Egg-white in large doses is itself injurious to the kidney of animals,
      but this slight primary toxicity is probably greatly enhanced through previous
      sensitization of the animal.

PMID- 19867741
TI  - THE RELATION OF THE AURICULAR ACTIVITY FOLLOWING FARADIZATION OF THE DOG'S
      AURICLE TO ABNORMAL AURICULAR ACTIVITY IN MAN.
AB  - The tumultuous auricular activity which follows faradization of the auricles of
      mammals and which has been variously described, could be distinctly seen to
      consist almost constantly in our experiments on dogs of true fibrillatory
      movements of the separate muscle fibers coexisting with a rapid auricular
      tachycardia. During peripheral stimulation of the right vagus nerve the true
      fibrillation alone existed, the tachycardia being inhibited. A comparison of the
      electrocardiograms from dogs with this abnormal auricular activity with those
      from patients with the type of cardiac arhythmia which has been attributed to
      auricular fibrillation, and from patients with so called auricular flutter,
      indicates that the auricular activity in patients with either of these conditions
      differs somewhat from that usually seen in the faradized auricles of the dog in
      our experiments. The auricular activity of the cases of cardiac arhythmia is
      apparently true fibrillation, similar to that seen in the faradized auricles of
      the dog during right vagus stimulation. The electrocardiograms from cases of so
      called auricular flutter usually give no evidence of auricular fibrillation, and
      the auricular activity seems to consist of tachycardia alone. Fibrillation may
      apparently coexist with the tachycardia in some cases, when the auricular
      activity seems to resemble closely that usually seen in the dog after auricular
      faradization. During peripheral stimulation of the left vagus nerve, the
      electrocardiograms obtained after auricular faradization show changes which
      render them more nearly similar to those obtained from patients with auricular
      flutter. The facts that the auricular activity of the faradized auricles of the
      dog may apparently pass spontaneously into that closely resembling auricular
      flutter in man, that it may be changed into true fibrillation by right vagus
      stimulation, and that the abnormal auricular activity in man passes from a state
      of flutter to that of fibrillation in a similar manner, may be taken as evidence
      for the belief that auricular fibrillation and auricular flutter in man are
      closely allied cardiac disorders.

PMID- 19867742
TI  - THE EFFECT OF MORPHIN ON THE MECHANISM OF THE DOG'S HEART AFTER REMOVAL OF ONE
      VAGUS NERVE.
AB  - The effect of injecting morphin in right vagus dogs is to slow or practically to
      stop auricular systoles, the circulation being maintained by ectopic,
      independent, ventricular contractions. The function of conduction is, relatively
      speaking, undisturbed. The fact that after morphin injections there is little or
      no disturbance of conduction in right vagus dogs and a profound one in left vagus
      dogs may be used as a factor in distinguishing between them, especially when
      there is a reduction in rate greater than usual in left vagus dogs. The effect on
      left vagus dogs is to slow the rate of the auricles moderately and to increase
      the length of conduction, so that partial auriculoventricular block or complete
      auriculoventricular dissociation results. These are precisely the results that
      have been obtained by faradic stimulation of one vagus nerve, the other being
      divided. There are slight differences in the results obtained between the two
      methods, but the explanation for these is probably to be found in the differences
      in the nature of the experiments. When faradic stimulation is employed, the
      stimulus is applied a short time only,-in our experiments for periods not longer
      than ten seconds. The occurrence of the maximum effect is sudden and does not
      provide for a gradual introduction of the ventricles to new conditions. In right
      vagus stimulation the ventricles usually stop beating. A gradual introduction is,
      however, not always necessary, as may be seen in figures 5 and 6 of the paper (4)
      already quoted, where idioventricular rhythms began without delay. Another
      difference between the two methods is found in the degree of effect produced on
      stimulating the left vagus; in the faradic method the change in conduction varies
      from mere lengthening to a condition so profound that complete dissociation
      results; these degrees have been described. The morphin method usually produces
      only incomplete dissociations. Twice only was complete dissociation produced. The
      similarity between the results of the two methods is sufficiently close to render
      it likely that in obtaining them an identical mechanism in the heart is involved.
      It may, therefore, be concluded that the inconstant action of the vagus resulting
      from morphin injections, called "ungleichartig" by Einthoven and Wieringa,
      appears so on account of the fact that the predominating effect of morphin may be
      exercised now on one and now on the opposite cardio-inhibitory system, and not,
      as was suggested, on account of a shifting of predominance from one to another of
      the fiber tracts in the vagi themselves. The explanation offered as the results
      of this series of experiments differs from theirs. The results obtained
      substantiate the conclusion reached in the former series, that the two vagi act
      differently. A fact relating to the mechanism of the right vagus nerve can now be
      added, from a consideration of the cardiac mechanism in right vagus dogs, namely,
      that derangements in conduction result, to a very slight extent only, as the
      effect of the influence of the right vagus nerve Although no solution of the
      production of the extreme grades of sinus irregularity seen in morphin
      intoxication is offered, the failure of this rhythm to be converted into a more
      profound irregularity may be explained. There seems little doubt that the
      occasion for the occurrence of an independent ventricular rhythm in these
      experiments was due to the slowness of the auricular rate resulting from morphin
      injection. But in the cases of sinus irregularity (Nos. 683, 685, and 700), the
      rate of the auricles was never sufficiently low for the ventricles to initiate an
      independent rhythm. The lowest rates recorded in them were 66.3 (No. 683), 85.7
      (No. 685), and 91.4 (No. 700), and it appears that before an independent
      ventricular rhythm occurred in any of the experiments, the auricular rate had
      always fallen below 41 (Nos. 686, 688, 697, 698, 706, 715, and 721). On the other
      hand, the ventricular rates in the cases of sinus irregularity were higher than
      the highest idioventricular rates observed and no advantage could consequently
      have been gained by the onset of a new rhythm. No. 683 was an exception, but the
      rate in this case exceeded the idioventricular rates of all but Nos. 702 and 706
      and was only 11.1 beats below that of the highest recorded. Whether sinus
      irregularity itself is a morphin irregularity the result of a sino-auricular
      block, in the sense of Eyster and Meek, has already been discussed.

PMID- 19867743
TI  - THE PREDOMINANT INFLUENCE OF THE LEFT VAGUS NERVE UPON CONDUCTION BETWEEN THE
      AURICLES AND VENTRICLES IN THE DOG.

PMID- 19867744
TI  - DOES CARDIAC RHYTHM ALONE DETERMINE HUMAN BLOOD PRESSURE VARIATIONS?
AB  - Changes in cardiac rhythm are not the only determinants of blood pressure
      variations in man. They play a part in the variations of systolic and diastolic
      pressures, the relative importance of which depends on the degree of arhythmia
      present and on the depth of respiration which, in itself, causes the systolic and
      diastolic pressures to decrease during inspiration and increase during
      expiration. No degree of rate variation can be regarded as a type. The cases
      range from those in which respiration governs the change of pressures entirely
      through those where more or less complicated mixtures of heart rate and
      respiratory influences intermingle to those in which extreme cardiac variations
      alone determine the pressure changes. The emphatic insistence of Henderson and
      his collaborators that heart rate changes play a more important part than is
      commonly recognized in man is true in many cases. That, in certain cases, it is
      the only determining influence may also be admitted, but they are in the
      minority. The majority show the intervention of a respiratory influence which
      controls, at least, the variations of systolic pressure. In the light of these
      results, the doctrine that, in man, an effective venous pressure exists
      sufficient during all respiratory phases to insure superimposable beats, must be
      subjected to further reinvestigation.

PMID- 19867745
TI  - EXPERIMENTAL HYDROCEPHALUS.
AB  - Internal hydrocephalus can be produced experimentally by injecting a foreign
      substance into the ventricles. In these experiments, aleuronat, a granular,
      insoluble material, has caused an acute inflammatory reaction, characterized in
      the first week by an exudate consisting largely of polynuclear leucocytes. Later
      the picture is one of a chronic process; polynuclear cells are replaced by
      lymphoid and large mononuclear cells and there is proliferation of the connective
      tissue in the choroid plexus. Proliferation of the ependyma occurs in the first
      week but becomes more advanced in the second and third weeks, and there is
      increase in neuroglia more marked in the long continued experiments. Ordinarily
      when aleuronat is injected into a serous cavity, the pleural cavity, for example,
      abundant accumulation of fluid takes place in twenty-four to forty-eight hours,
      and at the same time polynuclear leucocytes collect. In the experiments in which
      the irritant was injected into the ventricle of the brain there was little or no
      dilatation apparent in the first week; absence of dilatation in all probability
      is due to the free outflow of the fluid. When obstruction occurs during the
      chronic stage of the inflammatory process dilatation of the ventricle follows.
      Choked disc and other symptoms of increased intracranial pressure accompany
      experimental hydrocephalus. Dilatation occurs slowly and reaches a maximum in
      about two months. In some of the experiments of longer duration obstruction can
      be demonstrated in gross or microscopically. Obvious obstruction has not been
      found by gross examination in all instances, but in the experiments in which
      India ink was injected into the ventricle before death obstruction to outflow was
      very readily demonstrated. The third and fourth ventricles were in all instances
      filled with the pigment, but none appeared on the surface of the brain, whereas
      in normal dogs the entire surface, especially the base, became deeply pigmented.
      Obstruction to the circulation of cerebrospinal fluid causing internal
      hydrocephalus may occur at the foramen of Monro, in the aqueduct of Sylvius, or,
      doubtless with greatest frequency, at the foramen of Magendie.

PMID- 19867746
TI  - OBSERVATIONS ON THE GROWTH OF BACTERIA ON MEDIA CONTAINING VARIOUS ANILIN DYES.
AB  - Gentian violet and allied anilin dyes have a similar influence on bacterial
      growth, dividing bacteria into two groups corresponding in general to their
      reaction to the Gram stain. Among Gram-negative bacteria a strain is occasionally
      encountered which will not grow on violet agar, differentiating it from other
      members of the same species or variety. The reaction is quantitative, although
      the quantitative character is more marked with some species than with others. The
      streptococcus-pneumococcus group differ from other Gram-positive bacteria in
      their ability to grow in the presence of amounts of dye sufficient to inhibit the
      other species. The dysentery bacillus group shows marked variation in the
      presence of dyes. In the case of fuchsin the variation approaches closely a
      specific difference between the dysentery and paradysentery groups. The
      variations of the latter groups with other dyes show no correlation with the
      common differential characteristics. A closer study might reveal variations in
      other characteristics which would parallel the different reactions to dyes.
      Decolorization with sodium sulphite robs the dyes of some of their inhibitive
      powers.

PMID- 19867747
TI  - THE ACID AGGLUTINATION OF PNEUMOCOCCI.
AB  - Eight strains of pneumococci of serological type 1, eight strains of type 2, and
      eleven strains belonging to neither type have been tested by the method of acid
      agglutination. Strains belonging to the two typical groups have, as a rule,
      narrow zones of agglutination. The optimum hydrogen ion concentrations are
      different in the two cases. Other pneumococci have broad zones or, in a few
      cases, narrow zones not coincident with those occupied by the typical organisms.
      The agglutination of most of the pneumococci of types 1 and 2 is extremely
      susceptible to the inhibiting action of salts. This is not true of the other
      pneumococci. Old broth cultures may show an optimum hydrogen ion concentration
      different from that shown by young broth cultures.

PMID- 19867748
TI  - AN IMMUNOLOGICAL STUDY OF PNEUMOCOCCUS MUCOSUS.
AB  - 1. The organisms described by Schottmuller under the name Streptococcus mucosus
      represent a well defined group with characteristics which indicate a closer
      relationship to the pneumococci than to the streptococci. 2. The members of this
      group are specifically agglutinable when treated according to the method of
      Porges. They do not agglutinate when subjected to the usual agglutination
      methods. 3. Complement fixation experiments with these organisms, compared with
      similar experiments with two varieties of pneumococci and two streptococci,
      indicate that they are closely related to the pneumococci. 4. No protection of
      mice against Pneumococcus mucosus by means of specific immune sera could be
      demonstrated. 5. The name Pneumococcus mucosus should be adopted for this group
      instead of Streptococcus mucosus.

PMID- 19867749
TI  - ON THE CAUSATION BY FILTERABLE AGENTS OF THREE DISTINCT CHICKEN TUMORS.
AB  - A causative agent has been separated from three chicken tumors of very different
      sort, namely a spindle-celled sarcoma, an osteochondrosarcoma, and a spindle
      celled sarcoma peculiarly fissured by blood sinuses. This was accomplished after
      the tumors had been transplanted repeatedly and their malignancy enhanced. Each
      of the tumor-producing agents is a distinct entity in that it gives rise only to
      growths of the precise kind from which it has been derived. All pass through
      Berkefeld cylinders impermeable at the same test to small bacteria, and two of
      the three retain their activity in tumor tissue that has been dried or
      glycerinated. All are strikingly dependent for their action on derangement of the
      tissue with which they are brought in contact. The general findings strongly
      suggest that the agents are of about the same size, and of the same natural
      class. It is perhaps not too much to say that their recognition points to the
      existence of a new group of entities which cause in chickens neoplasms of diverse
      character.

PMID- 19867750
TI  - FURTHER OBSERVATIONS AND EXPERIMENTS ON GOITRE (SO CALLED THYROID CARCINOMA) IN
      BROOK TROUT (SALVELINUS FONTINALIS) : III. ITS PREVENTION AND CURE.
AB  - 1. Goitre in fish is a non-infectious, non-contagious, symptomatic manifestation
      of a fault of nutrition, the exact biochemical nature of which has not been
      determined. 2. Feeding the highly artificial and incomplete diet of liver is the
      major etiological factor in bringing about this fault of nutrition which is at
      once corrected by feeding whole sea fish. 3. Water plays no essential part in the
      etiology, transmission, or distribution of the disease in the fish of this
      hatchery.

PMID- 19867751
TI  - OBSERVATIONS ON TETANY IN DOGS : RELATION OF THE PARATHYROIDS TO THE THYROID;
      RELATION OF TETANY TO AGE, AMOUNT OF PARATHYROID TISSUE REMOVED, ACCESSORY
      PARATHYROIDS, PREGNANCY, LACTATION, RICKETS, SULPHUR, AND DIET; RELATION OF
      PARATHYROIDS TO SUGAR TOLERANCE; EFFECT OF CALCIUM SALTS.
AB  - Accessory parathyroid tissue unassociated with the thyroid lobes is present in 5
      to 6 per cent. of dogs. For the determination of the presence of accessory
      parathyroid tissue there are two tests: (1) the anatomical, often entailing
      serial sections of the neck and upper thoracic structures, and (2) the
      biological, consisting of the daily use of some calcium salt for two to three
      weeks. The latter is more easily carried out and more accurate. In the absence of
      all parathyroid tissue calcium salts will not save the animal's life, while in
      the presence of active parathyroid tissue calcium will save it. Many factors
      other than the amount of parathyroid tissue removed influence the onset of
      tetany, among which are age, pregnancy, lactation, rachitis, the administration
      of sulphur, and diet. Pregnancy and lactation tetany in dogs resembles in all
      essentials parathyroid tetany. Our observations are in harmony with those who
      hold that the thyroid and parathyroid are independent structures as regards their
      anatomy, physiology, and pathology. The removal of the parathyroids immediately
      lowers alimentary sugar tolerance, but rarely to the degree of constant
      glycosuria. In sharp contrast with thyroid substance in myxedema, the feeding of
      parathyroid substance fresh or dried by mouth is of no value in the parathyroid
      tetanies of dogs. Calcium salts have a striking palliative effect on parathyroid
      tetany and preventative action in tiding over otherwise fatal cases, but are in
      no sense curative. The mode of action is unknown. There is some evidence that
      calcium salts directly influence the parathyroid gland.

PMID- 19867752
TI  - ON THE SURVIVAL AND TRANSPLANTABILITY OF ADULT MAMMALIAN TISSUE IN SIMPLE PLASMA.
AB  - 1. Growth of adult mammalian tissue can be prolonged by transference to fresh
      medium. 2. In a few cases this growth can be continued for ten or eleven
      generations up to a period of forty days. 3. In the majority of cases growth
      ceases after three or four generations. 4. After the first transference growth is
      increased, but in subsequent generations it gradually diminishes and ultimately
      ceases altogether.

PMID- 19867753
TI  - THE BEHAVIOR OF ELASTIC TISSUE IN THE POSTFETAL OCCLUSION AND OBLITERATION OF THE
      DUCTUS ARTERIOSUS (BOTALLI) IN SUS SCROFA.
AB  - A study of the histogenesis of elastic tissue in the embryonic ductus arteriosus
      of Sus scrofa is in accord with the theory that elastic fibrils are directly
      differentiated in the outlying portion of the protoplasm of the early connective
      tissue cell. In the occlusion of the postfetal ductus arteriosus of Sus scrofa
      there is early a hypertrophy of the internal elastic membrane. Subsequently there
      takes place a marked delamination of the thickened internal elastic membrane in
      the production of new and independent elastic fibers and lamellae. The formation
      of new elastic fibers from preformed elastic tissue is most abundant where the
      postfetal contraction of the ductus arteriosus is least marked. These new elastic
      fibers play an important part in the occlusion of the lumen of the postfetal
      ductus. Aside from the extensive formation of elastic fibers from preformed
      elastic tissue, in the occlusion of the lumen of the postfetal ductus arteriosus
      of Sus scrofa, there are also some elastic fibrils formed from non-elastic
      elements, apparently from connective tissue cells. In some recent preliminary
      work on ligations of the common carotid artery there was found, after an interval
      of from eight to twelve days, at some points between the ligatures, a slight but
      obvious cellular thickening of the so-called subendothelial stratum. Some of
      these connective tissue cells may have wandered from the other coats of the
      vessel, through the inner elastic membrane into the subendothelial stratum;
      others may have proliferated from cells in situ. Specific stains revealed near
      the periphery of some of these cells, i. e., in the outlying portion of the
      exoplasm, very delicate elastic fibrils, apparently the product of protoplasmic
      activity.

PMID- 19867754
TI  - INTESTINAL OBSTRUCTION : III. THE DEFENSIVE MECHANISM OF THE IMMUNIZED ANIMAL
      AGAINST DUODENAL LOOP POISON.
AB  - Dogs may be immunized against lethal doses of the duodenal loop poison by means
      of small doses of the loop fluid from dog or cat and by material obtained from
      human cases of intestinal obstruction. The immunity is transient and may
      disappear within a few weeks. Dogs immunized by repeated doses of loop fluid show
      a definite resistance against the intoxication of a closed duodenal loop and may
      survive twice the usual period. A dog that recovers from simple intestinal
      obstruction may possess a strong resistance to the intoxication of a closed
      duodenal loop, thus indicating a similar type of intoxication in the two
      conditions. The sera of immune dogs are inactive when incubated with duodenal
      loop fluid. The organ extracts and emulsions (liver, spleen, lung) of immune dogs
      rapidly destroy the loop poison during incubation in vitro. This destructive
      property is possessed by a clear filtrate of the digested immune organs,
      excluding adsorption, and is lost after long periods of incubation (twelve
      weeks). We are investigating the action of this immune organ extract to determine
      whether it can destroy the closed-loop poison in vivo and perhaps be of value in
      treatment.

PMID- 19867755
TI  - INTESTINAL OBSTRUCTION : IV. THE MECHANISM OF ABSORPTION FROM THE MUCOSA OF
      CLOSED DUODENAL LOOPS.
AB  - Intoxication is evident in a drained duodenal loop whether it opens externally or
      into the jejunum and may be associated with more or less immunity which can be
      demonstrated after a period of days. Intoxication with a closed duodenal loop is
      identical whether the loop is left empty at operation or filled with a lethal
      dose of loop fluid. This again emphasizes the fact that absorption of the poison
      is essentially from the mucous membrane rather than from the contents of the
      closed loop. The intoxication of a closed duodenal loop is not modified by the
      presence of bile, pancreatic juice, or gastric secretion. Cessation of the normal
      flow of intestinal fluids which bathe the mucous membrane may be essentially
      responsible for the perverted activity of the mucosa and secretion of a poisonous
      material into the blood. Animals may be slightly more resistant to closed or
      drained loops during the warm months, which may be explained by the increased
      loss of body heat in the colder months. This indicates that cases of acute
      intestinal intoxication with subnormal temperature may be benefited by a generous
      supply of artificial heat.

PMID- 19867756
TI  - STUDIES IN TISSUE SPECIFICITY : II. THE ULTIMATE FATE OF MAMMALIAN TISSUE
      IMPLANTED IN THE CHICK EMBRYO.
AB  - Rat tumors and other tissues of foreign species grow actively in the chick embryo
      until the onset of a refractory period. Grafts of rat sarcoma established and
      growing actively at the onset of this period show a rapid cessation of growth
      between the 18th and 19th days of incubation. This is followed by a widespread
      degeneration of the rat cells and a marked activity of the connective tissue
      elements in the embryonal tissue round about. An occasional specimen may show
      small mononuclear infiltration or rarely accumulations of polymorphonuclear cells
      in the neighborhood of the strange tissue. During the 20th and 21st days the
      connective tissue capsule increases rapidly, invading the graft and replacing it.
      The foreign cells disintegrate rapidly and by the 22d day have practically all
      disappeared. The period at which the established graft begins to degenerate,
      namely the 19th to the 20th day of incubation, is the one on which grafts of
      foreign tissue will no longer take when implanted in the embryo. The cells at the
      edge of the graft of foreign tissue survive for a time. There is a rapid
      formation of a connective tissue capsule and an invasion of the grafts. The
      foreign cells here practically all have disappeared by the 22d day, leaving a
      mass of connective tissue. The absence of a round cell infiltration is the most
      marked difference in the process in the embryo as compared with that in the adult
      chicken. The process about the grafts in newly hatched chicks is characterized by
      a more active response of the connective tissue than in the adult and a more
      pronounced round cell infiltration than in the embryo.

PMID- 19867757
TI  - THE FUNCTION OF THE SPLEEN IN THE EXPERIMENTAL INFECTION OF ALBINO MICE WITH
      BACILLUS TUBERCULOSIS.
AB  - Infection of rats and mice with Bacillus tuberculosis (bovine type) develops a
      splenic tumor as a typical lesion. Removal of the spleen from mice (albino)
      greatly increases their resistance to the infection. This increased resistance
      cannot be explained at present. The infection in the splenectomized mice tends to
      remain localized as contrasted with an almost septicemic type of disease which is
      usual in the normal animal. The animals of each group that live more than thirty
      days are apt to present typical exudative lesions. The removal of the spleen does
      not therefore grossly change what may be called the capacity of the body for
      exudation.

PMID- 19867758
TI  - A CONTRIBUTION TO THE EPIDEMIOLOGY OF POLIOMYELITIS.
AB  - A strain of the poliomyelitic virus was propagated in monkeys for four years,
      during which time it displayed three distinct phases of virulence. The several
      phases covered different periods of time. At the outset the virulence was low,
      but by animal passages it quickly rose to a maximum; this maximum was maintained
      for about three years, when, without known changes in the external conditions, a
      diminution set in and increased until at the expiration of a few months the
      degree of virulence about equalled that present at the beginning of the passages
      in monkeys. The cycle of changes in virulence is correlated with the wave-like
      fluctuation in epidemics of disease which also consist of a rise, temporary
      maximum, and fall in the number of cases prevailing. And an explanation of
      epidemics of disease is inferred in variations or mutations among the
      microorganismal causes of disease affecting chiefly the quality of their
      virulence.

PMID- 19867759
TI  - A CONTRIBUTION TO THE PATHOLOGY OF EPIDEMIC POLIOMYELITIS.
AB  - The virus of poliomyelitis is neurotropic, and localizes, and probably is capable
      of multiplying in the extramedullary parenchymatous nervous organs. It has been
      demonstrated by inoculation tests in the intervertebral, Gasserian, and abdominal
      sympathetic ganglia. All the ganglia show histological lesions, more or less
      severe, similar to those of the spinal cord and brain. The severest occur in the
      intervertebral ganglia, those next in severity in the Gasserian, while the
      mildest appear in the abdominal sympathetic ganglia. The interstitial lesions
      predominate over the parenchymatous, and in preparalytic stages the
      intervertebral ganglia show interstitial lesions, especially pronounced at the
      pial covering. Epidemic poliomyelitis is a general disease of the nervous system,
      although the most prominent and important symptoms are those following injury to
      the motor neurones of the spinal cord and brain. The virus of poliomyelitis is
      highly resistant to glycerin, in which it survives for more than two years; to
      0.5 per cent. phenol, in which it survives for more than one year; while it
      succumbs after having been kept frozen constantly for several months. It is
      unsafe to employ phenol to modify the virus of poliomyelitis for the purpose of
      active immunization. The cerebrospinal fluid of convalescents tends to be devoid
      of the neutralizing immunity principles for the virus of poliomyelitis, although
      they may exceptionally be present within this fluid. Doubtless the immunity
      principles are not produced locally in the nervous tissues, but elsewhere in the
      body, and are carried to the nervous organs by the blood.

PMID- 19867760
TI  - A NOTE ON THE ETIOLOGY OF EPIDEMIC POLIOMYELITIS.
AB  - The globoid bodies, or minute microorganisms, cultivated from the central nervous
      organs of human beings and monkeys that have succumbed to poliomyelitis, may be
      detected in the incubated brain tissues of infected monkeys in forms indicating
      post-mortem multiplication. Incubating the poliomyelitic tissues in kidney
      ascitic fluid culture medium and then crushing them is a more certain method for
      obtaining cultures of the organism. Identical bodies have been detected in blood
      films prepared on the twelfth day of the acute attack, from a paralyzed
      poliomyelitic monkey inoculated intraspinously. The same organism has been
      cultivated from the blood of a monkey that had received intravenously a large
      dose of a Berkefeld filtrate of poliomyelitic virus. No other microorganisms were
      detected either in the sections of the brain or in film preparations of the
      blood. These observations tend therefore to confirm the etiological relationship
      between the minute microorganism and epidemic poliomyelitis suggested by the
      successful cultivation and inoculation experiments reported by Flexner and
      Noguchi.

PMID- 19867761
TI  - INTRASPINOUS INFECTION IN EXPERIMENTAL POLIOMYELITIS.
AB  - By intraspinous injections of specimens of poliomyelitic virus of suitable
      virulence infection can be caused regularly in Macacus rhesus monkeys. The virus
      passes from the subarachnoid spaces into the nervous tissues in which it
      multiplies, and into the blood. The constant involvement of the pia-arachnoid
      membranes in poliomyelitis, even when no paralysis occurs, and the fact that
      infection can readily be produced by intraspinous inoculation suggests anew that
      in the pathogenesis of poliomyelitis the interstitial tissue changes within the
      meninges, blood vessels, and ground substance play a determining part. While the
      virus injected into the subarachnoid spaces can be demonstrated there by
      inoculation tests forty-eight hours after the injection it can no longer be
      detected on the sixth day, at a time when the first symptoms of infection make
      their appearance. The failure of the cerebrospinal fluid from human and
      experimental cases of poliomyelitis to produce the disease when inoculated into
      monkeys is due to the fact that the virus is either fixed by the nervous tissues
      or passes into the blood.

PMID- 19867762
TI  - THE RELATION TO THE BLOOD OF THE VIRUS OF EPIDEMIC POLIOMYELITIS.
AB  - Specimens of human blood taken during the paralytic stage of poliomyelitis and
      post mortem have proved not to be capable of infecting Macacus monkeys. Specimens
      of monkey blood taken at various stages of experimental poliomyelitis have not
      proved as a rule to be capable of infecting monkeys. In a single instance, among
      ten tests, infection was secured with a specimen of blood removed at the
      beginning of the paralysis on the seventh day following an intracerebral
      inoculation. When suspensions of the spinal cord from a paralyzed monkey have
      been injected into the brain or simultaneously into the brain and spinal canal,
      the blood removed from one to forty-eight hours later failed to cause paralysis
      after intracerebral injection. When large volumes of active filtrate are injected
      into the circulation the blood remains infective for seventy-two hours at least,
      but may be no longer infective after ten days when the paralytic symptoms first
      appear. When, however, the filtrate is injected in smaller amount or when a
      filtrate of a less active virus is employed in large quantity, the blood either
      fails to convey infection or conveys it irregularly. It is only when overwhelming
      quantities of an active virus are injected into the blood that paralysis results.
      The injection of moderate doses is not followed by paralysis, although the virus
      may still be detected in a blood sample twenty-four hours after the injection.
      The existence of a mechanism capable of excluding the virus within the blood from
      the central nervous organs is therefore inferred. Infection is accomplished far
      less readily through the circulation than by means of the more direct lymphatic
      and nervous channels of communication with the central nervous system. Several
      series of feeding experiments conducted with the biting stable fly (Stomoxys
      calcitrans) resulted negatively.

PMID- 19867763
TI  - THE RELATION BETWEEN THE FAT CONTENT OF THE BILE AND FATTY CHANGES IN THE LIVER.

PMID- 19867764
TI  - SOAPS AS FERMENT-INHIBITING AGENTS : STUDIES ON FERMENT ACTION. X.
AB  - 1. Sodium soaps prepared from olive oil, croton oil, cod-liver oil, linseed oil,
      etc., have the property of inhibiting the action of trypsin and leucoprotease. 2.
      The activity of these soaps is dependent upon the degree of unsaturation of the
      fatty acids and is in proportion to their iodin value. 3. Saturation of the acids
      with a halogen (iodin) causes a loss of this property. 4. Soaps of the saturated
      fatty acids tested do not have this influence on ferments.

PMID- 19867765
TI  - FERMENT-INHIBITING SUBSTANCES IN TUBERCLE BACILLI : STUDIES ON FERMENT ACTION.
      XI.
AB  - 1. Tubercle bacilli contain unsaturated fatty acids which, when saponified, have
      the property of inhibiting the action of trypsin and leucoprotease. 2. In
      proportion to their iodin value these soaps are more active as inhibiting agents
      than the soaps prepared from linseed, olive, and cod-liver oils. 3. The activity
      of the soaps is dependent on the presence of unsaturated carbon bonds. 4.
      Saturation of the soaps with iodin destroys their inhibiting action. 5. Soaps
      probably play an important part in the production of the condition known as
      caseation in tuberculosis.

PMID- 19867766
TI  - A FURTHER STUDY OF NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE
      NEPHRITIS.
AB  - These studies, like all studies of the kidney, are difficult of interpretation
      because of the impossibility of producing a pure glomerular or pure tubular
      nephritis. Arsenic nephritis in its early stage is physiologically a vascular
      nephritis, but anatomically tubular, and shows in this stage almost no retention
      of nitrogen, although studies of urinary nitrogen indicate an increased
      catabolism. On the other hand, diphtheria nephritis in the early stages is
      anatomically a nephritis with marked involvement of the glomerulus anatomically,
      but it is physiologically a tubular form, and in this early stage there is little
      or no nitrogen retention although studies of metabolism indicate that protein
      catabolism is increased by the administration of diphtheria toxin. In both cases,
      however, there appears to come a time when the excreting power of the kidney is
      exhausted and nitrogen accumulation occurs in the blood. This is much less marked
      in the arsenic nephritis, with less tubular change, than in diphtheria toxin
      nephritis with its marked tubular degeneration. This same late accumulation of
      blood nitrogen is seen in immune serum nephritis, where the tubular changes are
      persistent and relatively more severe than the glomerular change. It might well
      be said that this is no argument for the influence of the tubules in the
      excretion of waste nitrogen because of the general exhaustion of the organism as
      a whole and of the kidney in particular, and that no positive conclusions can be
      drawn is indicated by the opening sentence of this summary. Tartrate nephritis
      was at first considered as purely tubular; but the appearance of occasional
      glomerular change, as mentioned by Wells in one of his animals, and the fact that
      the presence of precipitated albumen in the subcapsular space, pointed out by
      Pearce and Ringer, probably indicates an increased permeability of the tuft
      capillaries, all lead to the conclusion that although the tubular change
      predominates, there is, possibly, slight alteration of the glomerulus. This form
      of nephritis shows the most marked retention of nitrogen, persisting even though
      the glomeruli show almost no change, tending to clear up with the progress of
      time and evidently also with the repair of the tubular change, and bearing a
      direct relation to the dose of tartaric acid and presumably with the degree of
      tubular change. It must be remembered, however, that the nephritis in the cases
      of greatest retention is a very severe form, and this again clouds the
      physiological interpretation of the results. The study shows no reason for
      altering the conclusions of our earlier studies, but from the interpretation
      accorded above it appears to throw more stress on tubular change as determining
      nitrogen retention. It confirms in addition the value of the methods used for
      studies of this type.

PMID- 19867767
TI  - A NOTE ON NITROGEN RETENTION FOLLOWING REPEATED INJECTIONS OF NEPHROTOXIC AGENTS.
AB  - It is possible by means of repeated injections of uranium nitrate to produce in
      the cat a subacute or chronic nephritis which can progress to a fatal termination
      and show in its course increasing accumulation of non-protein nitrogen in the
      blood. This nephritis differs only slightly from the spontaneous chronic
      nephritis of the species. Repeated doses of diphtheria toxin produce a subacute
      form of nephritis with only temporary or slight retention, but nevertheless
      anatomically a well defined nephritis. The spontaneous nephritis studied
      resembles more closely that produced by uranium nitrate than that produced by
      diphtheria toxin both histologically and from the standpoint of blood analysis.

PMID- 19867768
TI  - A NOTE ON THE SPECIFICITY OF CYTOTOXINS.
AB  - 1. The plasma of guinea pigs treated by injections of rat sarcoma exhibits a
      toxic action in tissue culture preparations on the cells of both rat sarcoma and
      rat embryo skin. Similarly, the plasma of guinea pigs immunized by injections of
      rat embryo skin is toxic for cells of both types. 2. Injection of rat blood
      immunizes against both sarcoma and embryo skin, although not so strongly as
      injections of the two tissues. 3. Guinea pigs receiving injections of either
      chick embryo heart or intestine develop cytotoxic substances for both of these
      tissues. 4. The preceding findings tend to show that cytotoxins formed after the
      injection of different body tissues into a foreign species are to no extent
      specific for the tissues injected.

PMID- 19867769
TI  - AN EXPERIMENTAL STUDY OF THE HISTOGENESIS OF THE MILIARY TUBERCLE IN VITALLY
      STAINED RABBITS.
AB  - In our study of the histogenesis of the miliary tubercle developing inside the
      liver lobule in animals that have been stained vitally while inoculated with
      bovine tuberculosis, the controls enable us to recognize the manner in which the
      vital stain affects the liver. There is therefore no possibility of confusing the
      effects due to the organism with the effects due to the dye. It is, however, of
      interest to note that the effects are closely related. The vital stain alone is
      able to produce gradually some of the same changes that occur with far greater
      rapidity in experimental tuberculosis. Although in a few hours the Kupffer cells
      of tuberculous animals begin to react to the disease, in the case of normal
      animals stained vitally they do not do this until after the third or fourth dose
      of successive daily injections. After many days, nevertheless, the vital stain
      alone produces enlargement, proliferation, and separation of Kupffer cells so
      that these are converted into large free phagocytes which may possess one or
      several nuclei. These are the gigantic macrophages of chronically stained
      animals. In all our experiments we have used only acutely stained animals, so
      that the effects of the dye itself are never sufficient to produce the changes.
      In fact there is no evidence that the dye accentuates the changes appreciably
      during the time involved in the experiment. The dye, however, shows us the type
      of the cells entering into the tuberculous granuloma, for when fed to the body
      fluids in abundance trypan blue finds its way into all cells capable of receiving
      it. The vital stain is, as it were, a physiological test for the cells. Whatever
      the fundamental nature of the vital stain produced by trypan blue and the
      benzidine dyes may be, it is important that this reaction does not occur to any
      appreciable extent with mononuclear blood cells, and that it does occur
      emphatically in the case of the hepatic endothelium. By means of this vital test,
      then, the following phenomena occur when suspensions of tubercle bacilli are let
      into the portal blood stream. The organisms, swept on by the blood stream,
      finally lodge in the terminal branches of the portal vein, where they plug the
      vessels and continue to multiply. They injure the vessel wall and cause around
      them an exudative inflammatory process, and finally lead to the formation of
      tubercles situated not only in these areas but also within the liver lobule. The
      injury to the vessel wall is manifested in the early stages by the presence of
      vitally stained areas in its structure. The bacteria at the end of half an hour
      are found to be extracellular in clumps in the larger vessels, but already to
      some extent in the bodies of vitally stained Kupffer cells throughout the liver.
      Exudative inflammation manifests itself by the presence of a transitory
      accumulation of polynuclear leucocytes about the bacterial clumps, which may be
      seen as early as half an hour after the inoculation. They continue to be present
      in the larger cell clumps of the periportal areas for many days, but they are
      rapidly replaced by other cells, mononuclear in type, so that within a day the
      histological appearance of the portal plug has changed radically. The mononuclear
      cell thus entering most actively into the reaction is endothelial and not
      hematogenous in origin, the vital stain enabling us to make a clear distinction.
      This fact, evident in the portal plugs, is decisively shown in the case of
      tubercles developing within the liver lobule. Such tubercles probably result from
      the localization of individual organisms within the Kupffer cells, for the
      initial stages of such a probable cycle have been found by us. They consist of
      the occurrence of mitoses in certain Kupffer cells where the Ziehl-Nielson method
      shows a bacillus or several bacilli to have been phagocytized (figure 4). Rapid
      growth of the infected cell now takes place, and at thirty-six hours the
      multinucleated giant cell produced is largely separated from the other
      endothelium of the vessel wall. Many bacilli exist within the protoplasm of these
      cells (figure 5), which are especially distinguishable by their intense reaction
      to the vital stain. They have received trypan blue to such an excess that low
      power views of liver sections at the thirty-six hour stage show these cells as
      deep blue spots (figure 8). The origin of the giant cell from the Kupffer cell is
      evident not only from the above sequence and from the elective stain, but also
      from the fact that even when fully formed, protoplasmic strands still join it to
      its mother tissue,-the normal endothelium of the vessel. The strands entangle
      other cells in their meshes, especially mononuclear blood cells, one of which, of
      the polyblastic type, has homogeneous protoplasm and is not infrequently
      encountered in mitosis. These cells are unquestionably of importance in the
      lesion of tuberculosis. We have seen them abundantly in the capillaries soon
      after the inoculation and they also occur singly or in nests between the Kupffer
      cells and liver columns. They are, as a rule, free from the vital dye. They
      continue to be concerned in the further growth of the tubercle and with the
      connective tissue cells make the structure of older tubercles relatively complex.
      On the other hand, little complexity occurs in the structure of the young
      intralobular masses. The miliary tubercle formed at the end of thirty-six hours
      is composed of a giant cell, surrounded by epithelioid cells and by blood cells
      of the above polyblastic type. The giant cell and its so called epithelioid cells
      are electively stained and are exclusively derived from the hepatic endothelium.

PMID- 19867770
TI  - THE INDOPHENOLOXYDASE CONTENT OF TISSUES FROM RABBITS INFECTED WITH PNEUMOCOCCUS.
AB  - 1. The action of indophenoloxydase is generally diminished in the tissues (liver,
      renal cortex, heart muscle) of rabbits that die of pneumococcus septicemia. The
      diminution is more frequent and marked in the liver and kidney than in the heart
      muscle. 2. The diminished activity of indophenoloxydase becomes more evident when
      the tissues undergo autolysis. At 37 degrees C. this ferment is much more easily
      destroyed in the tissues of the infected animals than in those from normal
      control animals (tables I, II, III, and IV). Exceptions are rare and they occur
      chiefly with the heart muscle. 3. Normal rabbit tissues, inoculated in vitro with
      pneumococcus culture, do not lose their indophenoloxydase much more quickly than
      do the normal controls, when they are kept either at room temperature or at 37
      degrees C. (tables IV, V, VI, and VII). 4. It is therefore probable that the
      diminished activity of the indophenoloxydase of tissues from rabbits with
      pneumococcus septicemia is not due to the presence of the pneumococcus in these
      tissues, but that it is associated with a pathological change in the animal cell
      during life.

PMID- 19867771
TI  - A COMPARATIVE STUDY OF THE RATE OF PROTEOLYSIS OF TISSUES OBTAINED FROM RABBITS
      INFECTED WITH PNEUMOCOCCI AND OF TISSUES FROM NORMAL RABBITS.
AB  - Liver.-The amount of filterable nitrogen in the samples before autolysis is too
      variable, both in the normal livers and in the livers from pneumococcus
      infections in the rabbit, for a constant difference to be obtained. The amino
      nitrogen before autolysis is generally slightly increased in the livers of the
      infected animals, especially in the perfused specimens. Most of the experiments
      show an increased disintegration of the livers of the infected animals during the
      first stages of proteolysis (twenty to thirty hours), both in the non-perfused
      and the perfused specimens. This increased disintegration is generally more
      evident for the complex proteins (filterable nitrogen) than for the lower
      products (amino nitrogen). In the later stages the proteolysis of the blood
      containing livers of the normal and the infected rabbits tends to an
      equalization, or the relations reverse, the proteolysis of the normal samples
      becoming more advanced. In the perfused specimens the differences in the rate of
      proteolysis are the same as in the earlier stages. Kidney.-The rate of
      proteolysis shows no constant differences in the normal and infected tissues.

PMID- 19867772
TI  - THE EFFECTS OF EARLY EXTIRPATION OF THE THYMUS IN ALBINO RATS.
AB  - It has been shown that white rats may survive complete extirpation of the thymus
      for at least 131 days, even when the operation is performed within the first two
      weeks of life. Removal of the thymus does not produce an arrest or retardation of
      body growth and development. Qualitative changes in the skeletal system or teeth
      have not been found. In emaciated, weak animals osteogenesis is less active than
      in healthy rats, and the long bones are smaller and more delicate in structure.
      Such quantitative differences appear to depend upon the general nutrition, are
      equally pronounced in rats whose development is retarded from other causes, and
      cannot be referred specifically to loss of thymus function. No constant or
      characteristic alterations were detected in the spleen, testes, adrenals, or
      thyroid. Whatever functional correlations may exist between thymus and any or all
      of these organs are not evident from the occurrence of histological changes after
      the removal of the thymus. The relative proportion of lymphocytes in the blood is
      diminished for the first few weeks after the operation. We have not determined
      how long this alteration in the leucocytic formula persists. Since this paper
      went to press an article has appeared by Klose, describing briefly the results of
      thymus extirpation in pigs, goats, rats, and chickens. In rats thymectomized on
      the fourteenth day, there followed a progressive cachexia terminating in death
      after eight to ten weeks. Disturbances in ossification, which macroscopically and
      microscopically were identical with those of human rickets, developed also in the
      ribs and long bones. Some of Klose's litters failed to show these lesions, and
      this negative result is explained as having been due to the presence of thymic
      tissue within the thyroid gland. The observations of Klose are in direct
      contradiction to the negative results described in this paper. Since the possible
      presence of accessory thymus tissue either within the thyroid or elsewhere was
      carefully excluded in my experiments, the discrepancy between my findings and
      those of Klose cannot be explained upon this basis. Since this paper was sent to
      the publisher I have studied two additional rats which were killed 185 days after
      operation. Minute examination of a complete series of the neck organs, including
      the thyroid, failed to show any tissue which could be interpreted as thymus. The
      bones showed no rachitic changes. The infective origin of rachitic and
      osteomalacic lesions in rats has been established by Morpurgo. Although reference
      is made by Klose to Morpurgo's work, the data given by him do not enable one to
      judge whether this infection was definitely excluded.

PMID- 19867773
TI  - THE RELATION OF THE GASTRO-INTESTINAL TRACT AND CONTENTS TO THE BODY-WEIGHT IN
      RABBITS.

PMID- 19867774
TI  - ON THE NATURE OF THE OPSONIC SUBSTANCES OBNORMAL SERA.
AB  - Our experiments show that the albumen fraction, or end-piece, obtained by the
      dialysis of normal guinea pig serum possesses definite opsonic action. This
      action is often almost equal to that residing in the unfractionated alexin. It is
      evident, however, only if the reaction maintained during the experiments
      approximates that of the original serum. By the addition of small quantities of a
      weak sodium hydrate solution to the dialyzed serum we have been able to bring
      back opsonic action which was not evident in the same end-piece if simply
      rendered isotonic. Although our attention was called to the question of reaction
      by the work of Bronfenbrenner and Noguchi, like Liefmann, we have been unable to
      reactivate the hemolytic function of end-piece by alteration of reaction. Our
      experiments suggest that the opsonic action of the albumen fraction is enhanced
      by preliminary sensitization of the bacteria with heated normal serum and by
      persensitization of such bacteria with the globulin fraction. However, we cannot
      be positive of this, since the slight differences of phagocytic counts upon which
      such an opinion can be based, fall within the limits of what we consider our
      experimental error. The fact that the albumen fraction can exert opsonic activity
      upon bacteria but cannot hemolyze blood cells seems to us particularly
      interesting in the light of the fact that alexin can be absorbed by unsensitized
      bacteria but not by similarly untreated blood cells. The literature upon the
      relation of the alexin fractions to bacteria and the bactericidal effect is
      confusing in that contradictory results have been obtained by other workers. We
      are studying this phase of the problem with particular attention to the
      alkalinity or acidity under which the reactions are carried out. We think that
      our experiments do not point to a differentiation of normal opsonin from alexin,
      but we believe they indicate that the so called end-piece can enter to a slight
      extent into non-specific relationship with unsensitized bacteria, and it is
      therefore active, whereas it cannot enter into a similar relation to unsensitized
      cells. This conception, however, is tentatively made, since we are studying
      further the non-specific absorption of alexin or complement by unsensitized
      bacteria.

PMID- 19867775
TI  - OBSERVATIONS ON A STRAIN OF SPIROCHAETA PALLIDA ISOLATED FROM THE NERVOUS SYSTEM.
AB  - A strain of Spirochoeta pallida isolated from the nervous system has shown the
      following constant characters: (1) thick form; (2) the production of hard, well
      demarcated lesions with necrotic centers; (3) a characteristic location of the
      lesion; (4) a short incubation period; (5) a tendency to generalize with lesions
      of the skin and eye, following local inoculation of the testicle and scrotum. It
      is suggested that these characters constitute a definite strain of highly
      invasive power and that a classification of members of the pallida group may be
      made in accordance with this power.

PMID- 19867776
TI  - A NOTE ON NITROUS OXIDE AS AN ANESTHETIC IN ANIMAL EXPERIMENTATION.
AB  - Nitrous oxide, administered by means of the Gatch apparatus, as a preliminary
      anesthetic to ether has been found to be superior for the dog in rapidity of
      action, in promotion of ease of handling, and in absence of disorder; the
      anesthesia may be maintained solely by nitrous oxide in combination with oxygen;
      it is economical; and its use is instructive to students from closer imitation of
      current surgical methods.

PMID- 19867777
TI  - THE RAPIDITY OF THE INVOLUTION OF ACTIVE THYROID HYPERPLASIAS OF BROOK TROUT
      FOLLOWING THE USE OF FRESH SEA FISH AS A FOOD.

PMID- 19867778
TI  - A STUDY OF THE FERMENTS AND FERMENT-INHIBITING SUBSTANCES IN TUBERCULOUS CASEOUS
      MATERIAL : STUDIES ON FERMENT ACTION. XII.
AB  - 1. Caseous matter obtained from lymph glands which have not become secondarily
      infected contains substances which inhibit enzyme activity. These substances
      consist chiefly of soaps of the unsaturated fatty acids. 2. The inhibiting
      substances are present in relatively smaller amounts when the caseous matter has
      become secondarily infected. This is probably due to the dilution and washing out
      of the soaps. 3. Ferments are either entirely absent or present in very small
      amounts, unless the caseous matter has become secondarily infected. 4. Caseous
      material from the lungs contains smaller amounts of the inhibiting substances.
      This may be due to the acuteness of the process, which does not permit an
      accumulation of the soaps, or to the binding of the soaps with the ferments. 5.
      Ferments are present in caseous pneumonia. In the whole emulsion the ferments are
      less active in an alkaline than in an acid reaction; but removal of the soaps
      shows that those active in an alkaline reaction are also present in considerable
      amounts. 6. The previous treatment with iodin of caseous matter from both lymph
      glands and lungs increases the action of the trypsin.

PMID- 19867779
TI  - THE EFFECT OF DILUTION OF PLASMA MEDIUM ON THE GROWTH AND FAT ACCUMULATION OF
      CELLS IN TISSUE CULTURES.
AB  - 1. Dilution of plasma with isotonic solutions causes a more extensive migration
      in cultures of cells of the actively migratory type, such as those of spleen and
      bone marrow. Dilution with a limited quantity of distilled water produces the
      same effect. Less actively motile cells are influenced little or not at all by
      dilution. The effect on cells of the first type is probably due to the reduction
      in the quantity of fibrin in the clot producing lessened resistance to cell
      locomotion. 2. Dilution of plasma with either isotonic solutions or distilled
      water is without effect on cell multiplication, as is shown by records of the
      number of mitoses in living culture preparations. 3. Dilution of plasma with
      suitable quantities of Ringer's solution causes a marked diminution in the
      quantity of fat accumulated by the cells. This reduction is to be attributed to
      the decrease in the quantity of fat in the medium. The accumulation of fat by
      cells in cultures is therefore not to be regarded as the result of a cell
      degeneration, but as an accumulation, the source of the fat being the medium in
      which the cells are growing.

PMID- 19867780
TI  - A NOTE ON THE PATHOGENICITY OF TRYPANOSOMA LEWISI.
AB  - 1. Some strains of Trypanosoma lewisi may, at times, produce rapidly fatal
      infections in a large percentage of the rats infected. 2. In such strains of
      Trypanosoma lewisi, a sufficient degree of pathogenicity may persist to warrant
      the designation of these strains as pathogenic. 3. The pathogenicity of a given
      strain of Trypanosoma lewisi is not constant, but is subject to marked and even
      sudden variations.

PMID- 19867781
TI  - PENETRATION OF THE VIRUS OF POLIOMYELITIS FROM THE BLOOD INTO THE CEREBROSPINAL
      FLUID.
AB  - The virus of poliomyelitis introduced into the blood may pass indirectly by way
      of the cerebrospinal fluid to the interstices of the central nervous organs. To
      reach the cerebrospinal fluid the virus must first penetrate the barrier of the
      choroid plexus, which operation requires time. By the inoculation test, no virus
      was detected in the fluid at the expiration of 48 hours, only small amounts at
      the expiration of 72 hours, while at the expiration of 96 hours the virus had
      passed more freely. The virus was still detectable in the fluid at the onset of
      paralysis 19 days after the intravenous injection. Pathological conditions of the
      leptomeninges and the cerebrospinal fluid play an important part in the
      pathogenesis of epidemic poliomyelitis.

PMID- 19867782
TI  - ON THE SIGNIFICANCE OF THE SUBMILIARY MYOCARDIAL NODULES OF ASCHOFF IN RHEUMATIC
      FEVER.
AB  - 1. In rheumatic myocarditis, foci, termed submiliary nodules of Aschoff, are
      present which are characteristic of the rheumatic infection. 2. They are most
      frequently found in the walls of the left ventricle, the auricles usually
      escaping. 3. The nodules were found in three cases of chorea without joint
      manifestations, proving the close relation of this condition to rheumatism. 4.
      They were absent in fourteen cases of subacute bacterial endocarditis due to
      Streptococcus mitis. 5. They were not found in infections of the endocardium with
      the gonococcus, staphylococcus, streptococcus, or pneumococcus. 6. Even in the
      absence of a rheumatic history we believe, in accordance with Fraenkel, that the
      presence of Aschoff bodies signifies a previous rheumatic infection. 7. Aschoff
      bodies are not always found in rheumatic carditis, where the infection antedates
      death by a long period, but the healed remains, represented by sclerotic patches
      ("Schwielen"), are present. 8. We suggest that the cases of arthritis
      characterized by the presence of the submiliary nodules of Aschoff in the
      myocardium be placed in one group and called for the time being "rheumatism"; and
      the cases with articular manifestations, yielding positive bacteriological
      findings and no Aschoff bodies, should be classified according to the infecting
      microorganisms concerned, and not as rheumatism.

PMID- 19867783
TI  - EXPERIMENTAL FOCALIZED MYOCARDIAL LESIONS PRODUCED WITH STREPTOCOCCUS MITIS.
AB  - 1. By the intravenous injection into rabbits of Streptococcus mitis, we have
      produced focalized myocardial lesions which are identical with those caused by
      the injection of Streptococcus rheumaticus, and with those produced by Bracht and
      Wachter with Streptococcus viridans. 2. The lesions differ from those which we
      produced by injections of streptococci from the Chicago epidemic of sore throat
      (epidemic streptococcus). 3. The lesions are not identical with Aschoff bodies
      and are easily differentiated from them. They also differ from the foci produced
      by Jackson and Coombs, who describe their lesions as being either Aschoff bodies
      or similar formations. 4. The myocardial lesions of the rabbit appear to be
      caused by toxins liberated by the streptococci injected and not by the living
      organisms themselves. 5. The only point of similarity between the experimental
      lesions and those found in cases of rheumatic carditis in man is their focalized
      nature.

PMID- 19867784
TI  - EXPERIMENTAL ARTHRITIS IN THE RABBIT, PRODUCED WITH STREPTOCOCCUS MITIS.
AB  - 1. We have produced arthritis in 50 per cent. of the rabbits injected with
      Streptococcus mitis. 2. The character of the arthritis is identical with that
      produced by Micrococcus rheumaticus. 3. The exudate in and about the joints
      partakes of the same nature as that caused by Streptococcus rheumaticus. 4.
      Bacteriological studies show that Streptococcus mitis can be recovered from about
      one third of the affected joints. 5. Arthritis produced by other types of
      streptococci differs by reason of greater destruction of tissue, by being more
      permanent in character, and by the exudate containing large numbers of
      polymorphonuclear leucocytes. 6. The deduction of a distinct variety or species
      of streptococcus based upon the power to cause arthritis in rabbits is
      unwarranted.

PMID- 19867785
TI  - A STAGE IN THE MIGRATION OF THE ADULT TERTIAN MALARIAL PARASITE. EVIDENCE OF THE
      EXTRACELLULAR RELATION OF THE PARASITE TO THE RED CORPUSCLE.
AB  - 1. What appear to be certain definite stages in the migration of the malarial
      parasite from red corpuscle to red corpuscle may be demonstrated by thorough and
      persistent observations,-not minutes spent on each specimen, but many hours. 2.
      The migration of the malarial parasite from red corpuscle to red corpuscle gives
      a reasonable explanation of the loss of red corpuscles which cannot be accounted
      for by the destruction of the infected corpuscles at the time the parasites
      segment. 3. Migration to other red corpuscles is a satisfactory explanation of
      the ultimate fate of the young parasites seen in instances of multiple infection
      of single corpuscles. 4. In the light of the facts here presented, it would seem
      impossible to explain the instances of the parasites partly on and partly off
      degenerated red corpuscles as the result of technique. A stage in the migration
      of the parasite seems to me to be the probable interpretation of the phenomenon.
      5. A corpuscular mound encircled by an adult parasite, when seen at the periphery
      of the red corpuscle, should have the same significance and interpretation in
      reference to the extracellular relation of the parasite to the corpuscle, that it
      has when it is seen in connection with a young parasite. 6. The adult ring-form
      parasite should have the same interpretation as the young ring-form parasite. 7.
      Attachment to the external surface of the red corpuscles seems to me to be the
      only possible interpretation of the appearances of the parasites pictured in this
      article.

PMID- 19867786
TI  - THE NATURE OF SERUM ANTITRYPSIN : STUDIES ON FERMENT ACTION. XIII.
AB  - 1. The ferment-inhibiting action of the serum is due to the presence of compounds
      of the unsaturated fatty acids. 2. These fatty acid compounds may be removed from
      the serum by means of chloroform or ether. 3. Soaps prepared by saponifying the
      chloroform or ether extracts inhibit the action of trypsin. 4. The anti-enzyme
      action of the serum can be removed by filtering acid serum through kaolin, and
      can in part be restored by extracting the kaolin. 5. The decrease in strength of
      anti-enzyme in old sera is probably due to the action of the serum lipase. 6.
      Iodin, potassium iodide, or hydrogen peroxide remove the inhibiting action of the
      serum. 7. Soaps of the unsaturated fatty acids lose their ferment-inhibiting
      action when heated with serum at 70 degrees C.

PMID- 19867787
TI  - SEROTOXIN : STUDIES ON FERMENT ACTION. XIV.
AB  - 1. Sera from which the protective lipoids (unsaturated fatty acids) have been
      removed are toxic for the homologous animal. 2. The toxicity is due to three
      factors: (a) an alteration in the mechanism of coagulation, with resulting
      intravascular coagulation; (b) the exposure of the native serum proteins; (c) the
      formation of toxic split products (primary proteoses) by autolysis. 3. A definite
      maximum of toxicity can be determined, with a final stage of atoxicity due to
      continued autolysis. 4. Hirudin and sodium citrate do not protect animals. 5.
      Heating to 70 degrees C. destroys, or greatly lessens, the toxicity of the
      serotoxin, although the isolated proteoses are toxic after boiling. 6. The return
      of the extracted lipoids (saponified) neutralizes the toxicity. 7. Unsaturated
      soaps also neutralize the toxicity. 8. Sublethal doses produce extreme
      prostration, marked fall in body temperature, no eosinophilia, and an increase of
      antitrypsin. 9. Sublethal doses of rapidly prepared chloroform sera cause a
      decrease in coagulation time; sublethal doses of autolyzed sera cause an increase
      in coagulation time. 10. Previously injected animals are more resistant
      (increased antiferments). 11. Iodized animals are less resistant (decreased
      antiferments).

PMID- 19867788
TI  - FURTHER OBSERVATIONS ON THE GROWTH OF BACTERIA ON MEDIA CONTAINING VARIOUS ANILIN
      DYES, WITH SPECIAL REFERENCE TO AN ENRICHMENT METHOD FOR TYPHOID AND PARATYPHOID
      BACILLI.
AB  - Several green dyes show a marked selective action for members of the typhoid
      paratyphoid-colon group. This can be used for the enrichment of typhoid and
      paratyphoid bacilli present in feces. Forty dyes were tested with thirty strains
      covering all types of pathogenic bacteria. In general the dyes restrained the
      growth of the Gram-positive bacteria but had no effect on the growth of the Gram
      negative group.

PMID- 19867789
TI  - FACTORS OF RESISTANCE TO HETEROPLASTIC TISSUE-GRAFTING : STUDIES IN TISSUE
      SPECIFICITY. III.
AB  - It has been shown that the chick embryo offers suitable conditions for the growth
      of implanted tissues, whether these be embryonic or adult, of the same species or
      a foreign one. The chick at about the time of hatching develops a defensive
      mechanism against the tissue of foreign species. This resistance can be supplied
      to the embryo in the early stages if grafts of adult spleen or bone marrow are
      implanted. Under these conditions the embryo exhibits the same resistance to
      foreign tissue as does the adult, and presents the same histological
      manifestations about the graft. Furthermore, the same tissues, spleen and bone
      marrow, when grafted into an embryo with an established and growing rat tumor,
      bring about a retrogression and absorption of the foreign tissue. Other adult
      tissues do not supply this power to the embryo.

PMID- 19867790
TI  - FREE MALARIAL PARASITES AND THE EFFECT OF THE MIGRATION OF THE PARASITES OF
      TERTIAN MALARIAL INFECTIONS.
AB  - 1. The malarial parasite is extracellular throughout its life cycle and migrates
      from red corpuscle to red corpuscle destroying each before it abandons it; in the
      brief intervals between, the parasite is free in the blood serum; it does not
      remain long free, but almost immediately attaches itself to another red corpuscle
      by means of delicate pseudopodia. 2. The compact form of the tertian parasite is
      the type of free parasite most often observed; in this form the parasite may be
      seen not only in migration, but after quinine and in the cadaver. I believe the
      compact form to be the normal resting form of the parasite, all other forms being
      assumed in order to secure attachment and to obtain food. 3. Care must be taken
      not to confound free parasites having protoplasmic pseudopodia ready for
      attachment with the sexual flagellating parasites, whose flagella are composed of
      chromatin. 4. The malarial parasite can live for some time free in the blood
      serum, though under normal conditions there is no reason why it should remain
      free for any length of time, and there are certain periods in the life of the
      parasite when it must be admitted that it is free from the corpuscle and
      survives. If the parasite is, as I believe, attached to the external surface of
      the red corpuscle, it is constantly exposed to the action of the patients' serum.
      5. The destruction of more than one red corpuscle by each parasite would readily
      account for the severe and early anemia occurring in malarial infections. 6. Long
      continued treatment with quinine will eventually cause the death of all malarial
      parasites.

PMID- 19867791
TI  - THE ADRENALIN INDEX OF THE SUPRARENAL GLANDS IN HEALTH AND DISEASE.
AB  - The adrenalin index as used in this paper means the amount of adrenalin in
      milligrams per gram of gland. As in our hands the chemical colorimetric method
      has proved more accurate, these values rather than the physiological values will
      be given in the final analysis. The two adrenal glands in the same individual as
      a rule contain about the same amount of adrenalin per gram, but variations of 10
      to 20 per cent. are not unusual. Normal dogs show an index which may vary from
      1.2 to 1.8 milligrams. The dogs were killed by short ether anesthesia and
      bleeding from the carotid. Normal human beings, dying from trauma, rupture of
      aneurysm, etc., show an index of 0.35 to 0.50 of a milligram, when autopsy takes
      place a few hours after death. Deterioration of uncut glands or of a gland hash
      kept on ice in the dark is not rapid and rarely exceeds 10 per cent. in twenty
      four hours. Acute intoxication in dogs shows a low adrenalin index, especially
      the intoxication associated with intestinal obstruction and the closed intestinal
      loop. Intravenous injection of the poison found in closed duodenal loops
      sufficient to cause fatal shock causes a great drop in the adrenalin index, at
      times to one fourth normal or even lower. After recovery from a sublethal toxic
      dose the adrenalin index may rise rapidly to a point considerably above normal.
      The same may hold for recovery after chloroform poisoning. Anesthesia by
      chloroform or ether causes a drop in the adrenalin index depending upon the
      length of anesthesia and probably in part on the depth of anesthesia. Liver
      poisons (chloroform, phosphorus, hydrazine) cause a drop in the adrenal index to
      a low level, perhaps one half normal in acute cases. Pancreas extirpation with
      prolonged glycosuria and death produces a great drop in the adrenalin index
      (cat). There is evidence that this may hold in some cases of human diabetes. In
      man disease of one adrenal (tuberculosis) may be associated with an adrenalin
      index of double the normal value in the intact adrenal. Pernicious anemia is the
      only disease so far found to present an abnormally high adrenalin index, and the
      single case shows an index at least twice normal. This is of interest especially
      in relation to the views recently put forward to indicate that the spleen and
      adrenal may be concerned in the lipoid metabolism which is thought to be
      profoundly disturbed in this disease. Secondary anemia due to repeated hemorrhage
      or the intoxication of cancer or tuberculosis causes a fall in the adrenalin
      index. Cachexia due to neoplasm or tuberculosis may cause a marked fall in the
      adrenalin index, perhaps to less than one half of normal. Acute infections
      (typhoid fever), septicemia, peritonitis, and similar conditions may be
      associated with a normal adrenalin index or one somewhat below normal. Diseases
      of the kidneys, heart, or blood vessels associated with elevated blood pressure
      show no constant variation in the adrenalin index, which may be normal or
      slightly subnormal.

PMID- 19867792
TI  - OVARIAN INFECTION IN THE DOMESTIC FOWL AND DIRECT TRANSMISSION OF DISEASE TO THE
      OFFSPRING.
AB  - Ovarian infection and germinal transmission of disease have been conclusively
      demonstrated in our investigations of bacillary white diarrhea in the common
      domestic fowl. The disease, which has caused so much loss to the poultry industry
      in recent years, primarily affects young chicks that are but a few weeks old.
      Chicks which survive frequently become permanent bacillus carriers, the ovary
      being the important seat of infection. The eggs from such carriers often harbor
      the organism of the disease in the yolk. Chicks that develop in infected eggs
      become in turn infected, and have the disease at the time of hatching. The
      disease is transmitted to normal chicks through the infected droppings; thus an
      epidemic is produced, and the cycle of infection is completed. There is no
      evidence to indicate that germinal transmission through the male takes place. In
      view of the frequent negative results bearing on this question it seems probable
      that it does not.

PMID- 19867793
TI  - MORPHOLOGICAL AND DEVELOPMENTAL ANOMALIES OF A PATHOGENIC STRAIN OF TRYPANOSOMA
      LEWISI AND THEIR RELATION TO ITS VIRULENCE.
AB  - 1. The morphological and developmental anomalies of a pathogenic strain of
      Trypanosoma lewisi have been described to show the unusual character of the
      strain. 2. Especial attention is called to the spontaneous occurrence of
      ablepharoplastic forms of Trypanosoma lewisi. 3. It is pointed out that
      morphological anomalies were most pronounced in infections that showed unusual
      conditions of multiplication, and that such infections usually proved severe. 4.
      Finally, an appreciable correlation between the morphological and developmental
      characteristics and the virulence as manifested in these examples of infection
      with Trypanosoma lewisi has been suggested.

PMID- 19867794
TI  - ON CERTAIN SPONTANEOUS CHICKEN TUMORS AS MANIFESTATIONS OF A SINGLE DISEASE : I.
      SPINDLE-CELLED SARCOMATA RIFTED WITH BLOOD SINUSES.
AB  - Two spontaneous chicken tumors, unlike in several important respects, have given
      rise on transplantation to neoplasms of identical character. The spontaneous
      growth, No. 18, situated in the gizzard, was a spindle-celled sarcoma rifted with
      blood sinuses into which it extended, with result in what may be described as an
      intracanalicular pattern. The metastases, which were in the voluntary muscles,
      showed the same peculiar structure. Tumor 38, occurring in the subcutaneous
      tissue of the groin, was a solid, spindle-celled sarcoma of rather close texture,
      with few blood vessels. Here and there were small areas of softening, and at its
      center was a large degeneration cyst with ragged walls, containing a clear fluid.
      There were no metastases. The transplantation tumors from both growths have been
      characterized by slow growth, tendency to metastasize to the skeletal muscles
      without involvement of the lungs, and a structure which at one time is that of a
      very regular spindle-celled sarcoma containing many bands and ribbons of
      collagen, and at another that of a sarcoma rifted with blood sinuses like the
      spontaneous tumor No. 18. At present the two strains are practically
      indistinguishable in appearance and general behavior. Both are caused by
      filterable agents. The agent causing No. 38, unlike that causing No. 18, retains
      its activity in tumor tissue which has been dried or glycerinated; and in a
      Berkefeld filtrate it is much the more active in causing tumors. These
      differences can hardly be thought of as constituting a fundamental distinction
      between agents which, to judge from their effects, are almost undoubtedly
      different strains of a single disease cause. That chicken tumors of markedly
      different type have different filterable agents as their cause has been proved by
      experiments already reported. The present findings make it probable that, within
      certain limits, tumors of rather various character may be dependent upon a single
      agent. This assumption greatly simplifies the etiological problem. But the truth
      of the assumption for other instances than those described in the present article
      can only be determined by the study and comparison in many hosts of the disease
      complexes of which each spontaneous chicken tumor is to be considered as an
      individual expression.

PMID- 19867795
TI  - ON CERTAIN SPONTANEOUS CHICKEN TUMORS AS MANIFESTATIONS OF A SINGLE DISEASE : II.
      SIMPLE SPINDLE-CELLED SARCOMATA.
AB  - The forty-third spontaneous chicken tumor received at this laboratory strikingly
      resembles the first and has given rise on transplantation to an entirely similar
      series of neoplasms. Tumors of both strains are due to a filterable agent which
      remains active in the dried or glycerinated tissue.

PMID- 19867796
TI  - THE RECOGNITION OF THE CHOLERA VIBRIO.
AB  - Cholera-like non-agglutinating vibrios are invariably found in the intestinal
      contents of healthy persons, and frequently in the water of wells and rivers,
      during epidemics of cholera. Although many of these saprophytic vibrios are
      indistinguishable in morphology and cultural properties from the cholera vibrio,
      the negative reaction with an anticholera serum has readily differentiated them
      from the Asiatic vibrio. The biological polymorphism of the cholera vibrio has
      been suggested by the development of agglutination, by special methods of
      culture, in cholera-like vibrios. Confirmatory Pfeiffer reactions have not been
      obtained, as a rule, in these instances, probably because of the low virulence of
      the vibrio culture, although positive bacteriolysis in vitro (Bordet's test) was
      observed in some, and in others positive complement fixation and cross
      agglutination indicated the cholera nature of the vibrios in question. Although
      it cannot as yet be definitely proven, we are justified in suspecting that
      cholera-like vibrios which eventually develop agglutination properties are of a
      true cholera nature. It is probable that the production of agglutination
      antibodies in the serum brings about the development by the bacterial cell of
      defensive anti-agglutinins, resulting in the disappearance of agglutinating
      power. In the case of the water vibrios, changed physical conditions could bring
      about a similar alteration in biological properties. It may be said that the
      absence of agglutination in a vibrio isolated from a suspected source does not
      define conclusively its noncholera nature. In all probability among a number of
      cholera-like vibrios isolated from suspected sources a certain percentage will
      eventually be found to develop agglutination either during laboratory cultivation
      or by means of animal passage, and until subjected to a procedure that will
      induce the return of agglutination no vibrio can be regarded with assurance as of
      a truly saprophytic variety.

PMID- 19867797
TI  - THE CULTIVATION OF HUMAN TISSUE IN VITRO.
AB  - A strain of human connective tissue was kept in a condition of active life in
      vitro for more than two months. When a medium has been devised the composition of
      which is more constant, it is reasonable to suppose that human connective tissue
      can be cultivated in vitro for an indefinite period.

PMID- 19867798
TI  - PRESENT CONDITION OF A STRAIN OF CONNECTIVE TISSUE TWENTY-EIGHT MONTHS OLD.

PMID- 19867799
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : IX. THE CHANGES IN THE BONE MARROW AFTER SPLENECTOMY.
AB  - Splenectomy in the dog causes, as a rule, a transformation of the fatty marrow of
      the long bones to a richly cellular red marrow. During the early periods, one to
      three months, the change in the marrow is slight and either focal or peripheral;
      after six to twenty months the replacement of fat by marrow cells is complete or
      nearly so. Exceptions were, however, seen in four animals representing the 8th,
      9th, 10th, and 22d months, respectively. The evidence at hand does not support
      the theory that this hyperplasia is compensatory either to the anemia caused by
      splenectomy or to an increased hemolysis in the lymph nodes. It is possible that
      it may be a concomitant of the activity of the bone marrow in taking over, in the
      absence of the spleen, the function of storing and elaborating the iron of old
      blood pigment for future utilization by new red cells, but our studies do not
      fully support this view.

PMID- 19867800
TI  - PATCHING AND SECTION OF THE PULMONARY ORIFICE OF THE HEART.
AB  - These experiments show that it is possible to perform an operation, the object of
      which is to increase the circumference of the pulmonary orifice without involving
      much danger to the life of the animal. It is probable that operations of this
      type may come to be employed in the treatment of stenosis of the pulmonary artery
      in man.

PMID- 19867801
TI  - THE MECHANISM OF ANAPHYLATOXIN FORMATION : STUDIES ON FERMENT ACTION. XV.
AB  - 1. The unsaturated lipoids (serum antitrypsin) can be adsorbed from guinea pig
      serum, rabbit serum, and horse serum by kaolin, starch, agar, and bacteria. 2.
      Diphtheria toxin and cobra venom also reduce the serum antitrypsin, possibly
      because of their affinity for lipoids. 3. Anaphylatoxins represent sera rendered
      toxic by partial removal of serum antitrypsin. 4. The matrix of the protein split
      products lies in the serum proteins so exposed. 5. The amount of removal of serum
      antitrypsin depends on definite quantitative relations; very large amounts and
      very small amounts of adsorbing substances are least effective (kaolin, starch,
      and bacteria). 6. Bacteria previously treated with serum or with oils do not
      adsorb serum antitrypsin. 7. Bacteria treated with serum become more resistant to
      the action of trypsin.

PMID- 19867802
TI  - COMPLEMENT FIXATION TESTS IN CHRONIC INFECTIVE DEFORMING ARTHRITIS AND ARTHRITIS
      DEFORMANS.
AB  - 1. From a comparison of the results with arthritis deformans recorded in tables
      III, IV, and VI, and with the control cases recorded in table VII, one is
      justified in concluding that Streptococcus viridans is an infectious agent and
      excites the production of a complement-fixing substance (fixateur) in the
      organism in cases of arthritis deformans, and, therefore, Streptococcus viridans
      is the probable causative agent of the disease in many cases of arthritis
      deformans. Probably 40 per cent. and more of cases of arthritis deformans should
      be considered as chronic infective deforming arthritis. 2. Rarely the clinical
      manifestations of arthritis deformans may be due to gonococcus infection. 3. The
      serum from one case may react positively to two different organisms, most
      frequently to Streptococcus viridans and to gonococcus, when the reaction to the
      former should be considered the indicator of the causative agent, since with the
      latter infection is often latent in the genito-urinary tract. Incidence of
      gonococcus infection is high and the clinical manifestations of arthritis
      deformans are rarely produced by gonococcus infection.

PMID- 19867803
TI  - CONCERNING A POLYVALENT ANTIGEN FOR THE COMPLEMENT FIXATION TEST FOR
      STREPTOCOCCUS VIRIDANS INFECTION.
AB  - 1. Streptococcus viridans is of extremely low virulence for white mice and
      rabbits. 2. The serum of rabbits, after a series of intravenous injections of
      dead or living Streptococcus viridans, is poor in complement fixative substance
      (fixateur of Besredka) for Streptococcus viridans. 3. Antigens prepared from
      several strains of Streptococcus viridans are relatively poor in fixable
      substance. 4. The technique of complement fixation tests for infection with
      Streptococcus viridans is so laborious and difficult that the method will not be
      available for general clinical work.

PMID- 19867804
TI  - A NOTE UPON THE TECHNIQUE AND ACCURACY OF THE METHOD OF DOUGLAS AND HALDANE FOR
      CALCULATING THE DEAD SPACE IN BREATHING.
AB  - The determination of the percentage of CO(2) in the alveolar air, by the method
      of Haldane and Priestley, is sufficiently accurate for clinical purposes when the
      individual is at rest. It is evident, however, that an error may arise in the
      determination of the percentage of CO(2) in the alveolar air, due to the time
      during the forced expiration, short of the extreme limit, at which the sample may
      be unconsciously taken. This error can only be overcome by taking several
      samples. In individuals at rest having a tidal air below 425 cubic centimeters,
      the method of Douglas and Haldane for the calculation of the dead space gives
      approximately accurate results; with a tidal air above 425 cubic centimeters the
      results obtained may be wholly inaccurate. In patients with marked pulmonary
      tuberculosis so slight an effort as that involved in collecting the expired air
      tends to lower the percentage of CO(2) in the alveolar air. In collecting the
      expired air by the rubber bag method, it is absolutely essential that the bag be
      washed out with ordinary atmospheric air after every observation.

PMID- 19867805
TI  - EXPERIMENTAL OPERATIONS ON THE SIGMOID VALVES OF THE PULMONARY ARTERY.
AB  - Incision, suture, and cauterization of the sigmoid valves of the pulmonary artery
      have been performed successfully in dogs. In the first series of ten animals,
      there were only three accidents, probably from largely preventable causes,
      leading to the death of the animals.

PMID- 19867806
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : X. CONCERNING THE SUPPOSED REGULATORY INFLUENCE OF THE SPLEEN IN THE
      FORMATION AND DESTRUCTION OF ERYTHROCYTES.
AB  - 1. The blood of the splenic artery and vein shows either no differences, or only
      such slight irregular variations as may be due to the errors inherent in
      hematologic methods, or are common to arterial and venous blood of the general
      circulation. 2. The observation of Banti and Furno that free hemoglobin occurs in
      the blood of the splenic vein is not confirmed. 3. Extracts of the spleen have no
      definite hemolytic action in vitro. 4. Intraperitoneal injection of fresh saline
      extracts of the spleen causes in the dog a sharp increase in the number of red
      cells and the hemoglobin content which lasts for one or two days and may recur on
      a second injection. Extracts of liver, kidney, and erythrocytes similarly
      prepared do not give this effect. This observation supports Danilewsky's theory
      that the spleen may exert a stimulating effect upon the formation of red cells in
      the bone marrow. 5. On the other hand, the feeding of raw beef spleen to
      splenectomized dogs over long periods of time has no clearly defined influence in
      preventing the anemia which usually follows splenectomy.

PMID- 19867807
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : XI. THE INFLUENCE OF THE SPLEEN ON IRON METABOLISM.
AB  - Our studies give evidence of increase in the iron elimination in three of five
      dogs during a period of two weeks following splenectomy, but not in two other
      dogs. The occasional increased output of iron may have some relation to the
      anemia which occurs in the early weeks after splenectomy and which varies in
      degree in different animals. No evidence was secured of an increase in the iron
      output at 1, 9, and 20 months after splenectomy. From our own studies and from
      examination of the literature of the subject, we conclude that the spleen does
      not exercise a constant and important influence upon the iron metabolism of the
      body.

PMID- 19867808
TI  - THE EFFECT OF THE VARIATION IN THE OSMOTIC TENSION AND OF THE DILUTION OF CULTURE
      MEDIA ON THE CELL PROLIFERATION OF CONNECTIVE TISSUE.
AB  - For the first few days of cultivation of connective tissue in hypertonic,
      hypotonic, and diluted medium, cell proliferation was stimulated. The first
      outgrowths of new cells in the modified media did not occur sooner than in normal
      medium. In hypertonic medium the density of the area of cell proliferation
      appeared to be greater than the control, but in hypotonic or diluted medium there
      seemed to be no increase in actual mass over the control. These observations
      confirm the conclusions of Carrel and Burrows, as well as those of Lambert.
      Subsequent to the first few days of cultivation in hypertonic medium the area of
      cell proliferation decreased and in a short time conditions developed which were
      unfavorable to growth, and finally resulted in death of the culture, unless it
      revived before this stage. Hypotonic medium after about ten days no longer caused
      more extensive areas of proliferating cells; but instead, the extent of new
      growth gradually decreased, and the culture merely remained alive unless revived.
      In diluted medium the extent of the area of cell proliferation remained greater
      with no actual increase in mass. The area of cell proliferation which is observed
      during the first few days in a culture of fresh tissue recently extirpated does
      not indicate the actual influence of modified media. It was only after continued
      cultivation of strains of connective tissue in these modified media that their
      influence on cell proliferation was determined.

PMID- 19867809
TI  - THE CULTIVATION OF HUMAN SARCOMATOUS TISSUE IN VITRO.

PMID- 19867810
TI  - THE REMOVAL OF CALCIUM FROM THE BLOOD BY DIALYSIS IN THE STUDY OF TETANY.
AB  - We may devise a fluid containing practically all the inorganic diffusible
      constituents of the blood except calcium, and use it to dialyze normal blood in
      such a way as to remove from it a large part of its calcium. The dialyzed blood
      when perfused through an isolated extremity produces an extreme hyperexcitability
      of the nerves quite like that observed in tetany. Since perfusion with blood
      dialyzed in precisely the same way against a fluid of the same composition, but
      containing calcium in the proportion found in the normal blood, causes no
      hyperexcitability of the nerves, it is evident that the hyperexcitability is due
      to the lack of calcium. This effect can be attained in only a slight degree by
      replacing the blood of a whole animal with the dialyzed blood, since under the
      conditions of the experiment the tissues cannot be sufficiently depleted of their
      calcium. It seems probable that the parathyroid secretion is not removed by
      dialysis, but is returned to the body with the dialyzed blood. To bring this
      result into relation with the condition in tetany following parathyroidectomy,
      animals in tetany were bled and the blood was replaced in one case with normal
      blood, in the other with dialyzed blood poor in calcium. The normal blood
      immediately relieves the tetany and lowers the excitability, while the dialyzed
      blood does not. We therefore believe that this is a further proof that in the
      tetany of parathyroidectomy also the twitching and hyperexcitability of the
      nerves is due to lack of calcium in the blood and tissues.

PMID- 19867811
TI  - THE EXPERIMENTAL PRODUCTION OF NECROSIS OF THE LIVER IN THE GUINEA PIG.
AB  - Through the intravenous injection of various substances differing very much in
      character, multiple necrosis can be produced in the liver of the guinea pig. In
      the mouse the effect of these substances is absent or much less marked. Different
      substances seem to differ, however, in their power to produce necrosis. In
      control animals necrosis in the liver is much more rare. It is found especially
      in animals subjected to various injurious influences. The necrotic areas are
      usually situated between the portal and central areas of the liver acini. Their
      development is not due to thromboses interfering with the circulation in certain
      areas of the liver. They are probably due to a weakening of the circulation in
      the liver or to interference with the metabolism of the cells as a result of the
      injection of foreign substances. Mechanical factors (pressure on the liver cells)
      may have an additional effect. This necrosis may be compared etiologically to the
      acute gastric ulcers which can be produced through a great variety of toxic
      substances in the guinea pig.

PMID- 19867812
TI  - THE EFFECT OF THE INTRAVENOUS INJECTION OF SUBSTANCES AFFECTING TUMOR GROWTH ON
      THE CYCLIC CHANGES IN THE OVARIES AND ON PLACENTOMATA.
AB  - If six to seven days after copulation incisions are made under ether anesthesia
      into the uterus, and on the day following this operation one or several
      injections of hirudin are given, changes set in in the ovaries which correspond
      to those found at the time of ovulation; namely, a degeneration of all the
      follicles with the exception of the small ones. These degenerative changes are
      followed by the same developmental changes as in the normal cycle. This
      represents a second method of altering experimentally the periodicity of the
      sexual cycle, the first consisting in the early extirpation of the corpora lutea
      described previously by one of us. Under the same conditions intravenous
      injections of hirudin destroy in the large majority of cases the greater part of
      experimental placentomata through hemorrhages, and they prevent the remaining
      placentomatous areas from active proliferation, probably as a result of
      interference with the circulation. These injections may also cause abortion in
      pregnant animals. Intravenous injections of hirudin produce a tendency to
      hemorrhage at various places in the body, and these hemorrhages are prone to
      occur, especially in rapidly growing tissues, where the blood vessels are less
      resistant, as in tumors and in placentomata, also in the neighborhood of necrotic
      areas. In the stomach the hemorrhages may be followed by digestion of the tissues
      through the gastric juice. It is probable that there is a connection between the
      action of hirudin on the blood (coagulability and viscosity) and the tendency to
      hemorrhage. Withdrawal of blood, intravenous injections of distilled water,
      colloidal copper, nucleoproteid, or casein have no marked effect on the cyclic
      changes in the ovaries or on placentomata.

PMID- 19867813
TI  - A STUDY OF THE CIRCULATION OF THE KIDNEYS FOLLOWING LIGATION OF ONE URETER.
AB  - During the first four or five days after ligation of the ureter, the changes in
      the kidney are mainly degenerative in type. One week after ligation of the ureter
      connective tissue cells begin to appear infiltrating the kidney tissues. There is
      also an increase in the vascular cells of the glomeruli. These changes are well
      marked at the end of twenty days from the time of ligation. At the end of twenty
      days from the time of ligation there is also a marked hypertrophy of the control
      kidney, the glomeruli showing an average increase in size of twenty-five microns.

PMID- 19867814
TI  - STUDIES IN EXPERIMENTAL ATHEROSCLEROSIS : A PRELIMINARY REPORT.

PMID- 19867815
TI  - PARAMENINGOCOCCUS AND ITS ANTISERUM.
AB  - The parameningococci of Dopter are culturally indistinguishable from true or
      normal meningococci, but serologically they exhibit differences as regards
      agglutination, opsonization, and complement deviation. Because of the variations
      and irregularities of serum reactions existing among otherwise normal strains of
      meningococci it does not seem either possible or desirable to separate the
      parameningococci into a strictly definite class. It appears desirable to consider
      them as constituting a special strain among meningococci not, however, wholly
      consistent in itself. The distinctions in serum reactions between normal and para
      meningococci are supported by the differences in protective effects of the
      monovalent immune sera upon infection in guinea pigs and monkeys. It is therefore
      concluded that it is highly desirable to employ strains of parameningococcus in
      the preparation of the usual polyvalent antimeningococcic serum. It remains to be
      determined whether it is better to employ the parameningococci along with normal
      meningococci in immunizing horses, or to employ normal and para strains
      separately in the immunization process and to combine afterwards, in certain
      proportions, the sera from the two kinds of immunized horses.

PMID- 19867816
TI  - A STUDY OF THE METABOLISM OF CALCIUM, MAGNESIUM, SULPHUR, PHOSPHORUS, AND
      NITROGEN IN ACROMEGALY.
AB  - A distinct retention of calcium, magnesium, and phosphorus was noted, which was
      not accompanied by corresponding changes in general metabolism, as evidenced by a
      practical balance of nitrogen and sulphur. It is concluded that there is a
      primary disturbance in the metabolism of the mineral elements mentioned, with the
      probable formation of new bony tissue. The distribution of elements between urine
      and feces shows no abnormal variations. A suggestion is made as to the reasons
      for variable calcium output in the urine on a uniform diet.

PMID- 19867818
TI  - A METHOD FOR ESTIMATING THE BACTERIA IN THE CIRCULATING BLOOD IN RABBITS.
AB  - When rabbits are injected intravenously with a quantity of virulent streptococci
      or pneumococci sufficient to cause death within two to four days the septicemia
      takes a definite course with slight variations. The bacteria rapidly decrease in
      number from the time of the injection to from two to four hours, at which time
      the blood is sterile or contains only a few bacteria. Within five to six hours
      the bacteria reappear in the blood and steadily increase until the death of the
      animal. If the bacteria are less virulent, the same quantity of culture causes a
      chronic type of infection. The same initial decrease in the number of bacteria
      occurs. The reentrance into the blood is somewhat delayed, the septicemia does
      not reach the height obtained in the acute cases, and a second fall occurs within
      the course of a few hours. These rabbits show a low blood invasion or a sterile
      blood culture for several days. During this time they become emaciated to a
      marked degree. Then the low septicemia rapidly rises or the rabbit with a sterile
      culture develops a severe septicemia within a few hours and death takes place
      from a few hours to two days thereafter. In this type of infection local lesions,
      pericarditis, pleurisy, peritonitis, etc., are usually found. In the infections
      which run an acute course no gross lesions are found. If the bacteria are still
      less virulent they never reenter the blood after the initial disappearance and
      the rabbits remain in good condition. In order to obtain uniform results, the
      quantity of bacteria injected must not be so large that the bacterial substances
      See PDF for Structure carried in are sufficient to cause an intoxication of the
      animal. If the quantity of bacteria injected is below this point the course of
      the infection depends largely upon the virulence of the infecting organisms. Yet
      variations in the natural resistance of individual animals may be sufficient to
      cause quite marked irregularities in the course of the infection. Pneumococci can
      be standardized so as to produce a particular type of infection more easily than
      streptococci. In general infections such as those produced by streptococci and
      pneumococci the number of the bacteria present in the circulating blood at a
      given time supplies accurate and delicate information regarding the severity of
      the disease. When the object is to determine the degree of virulence of bacteria,
      or of the efficiency of an experimental therapeutic method, the mere physical
      condition and mere death of the inoculated animals are not sufficient and
      satisfactory guides to the desired information. The death of the inoculated
      animal and the recovery of the infecting bacteria at autopsy do not give complete
      information concerning the intensity and course of the infection occurring during
      life. A large number of bacteria found in the blood and tissues at autopsy do not
      necessarily prove the existence of a heavy infection before the onset of the
      death agony, since it is a well known fact that bacteria multiply with enormous
      rapidity, once the natural resistance of the animal has been overcome. Therefore,
      if merely the life and death of the animal and autopsy findings must serve as our
      only guides, we shall lose much incidental information, perhaps of fundamental
      value. This may be especially true as regards the search for curative substances.
      Again, the individual animals of the same species, age, and apparently of
      identical physical condition react to the aggressive force of the infecting
      organisms variously. This fact is readily found out by the injection of a series
      of rabbits with lethal quantities of bacteria per body-weight, and by making
      tests at various periods before death results, which, in the case of
      streptococci, ranges from one to six days. Consequently a method which enables
      the determination of the degree and progress of the infection at any desired
      period is of obvious advantage.

PMID- 19867817
TI  - CALCIUM METABOLISM AFTER THYRO-PARATHYROIDECTOMY.
AB  - The metabolism of calcium was studied in a man after complete removal of the
      thyroid and parathyroid glands. A slight retention of calcium (0.4578 of a gram
      of calcium oxide in the ten-day period) was noted. The urinary calcium excretion
      was low, averaging 0.0134 of a gram per day on a daily ingestion averaging 1.6736
      grams of calcium oxide. A slight increase was observed during the period of study
      in the calcium content of the blood. No symptoms of tetany were noted in the
      patient, who survived operation thirty-nine days. The low urinary and blood
      calcium values are taken to show deficient absorption of calcium, which may bear
      some relation to the decreased gastric secretion after parathyroidectomy.
      Attempts are made to explain the non-occurrence of tetany as due to the high
      calcium intake and to the development of a compensatory mechanism in which the
      pituitary body may play a part.

PMID- 19867819
TI  - LOCALIZATION OF THE VIRUS AND PATHOGENESIS OF EPIDEMIC POLIOMYELITIS.
AB  - The virus of poliomyelitis is capable of penetrating the retina without producing
      apparent injury, to reach the central nervous organs. The virus injected into the
      blood is deposited promptly in the spleen and bone marrow, but not in the
      kidneys, spinal cord, or brain. Notwithstanding the affinity which the nervous
      tissues possess for the virus, it is not removed from the blood by the spinal
      cord and brain until the choroid plexus and blood vessels have suffered injury.
      The intervertebral ganglia remove the virus from the blood earlier than do the
      spinal cord and brain. An aseptic inflammation produced by an intraspinous
      injection of horse serum facilitates and insures the passage of the virus to the
      central nervous organs, and the production of paralysis. The unaided virus, even
      when present in large amounts, passes inconstantly from the blood to the
      substance of the spinal cord and brain. When the virus within the blood fails to
      gain access to the central nervous organs, and to set up paralysis, it is
      destroyed by the body, in course of which destruction it undergoes, as a result
      of the action of the spleen and, perhaps, other organs, diminution of virulence.
      The histological lesions that follow the intravenous injections of the virus in
      some but not in all cases differ from those which result from intraneural modes
      of infection. In escaping from the blood into the spinal cord and brain, the
      virus causes a lymphatic invasion of the choroid plexus and widespread
      perivascular infiltration, and from the latter cellular invasions enter the
      nervous tissues. A similar lymphoid infiltration of the choroid plexus may arise
      also from an intracerebral injection of the virus. The histological lesions
      present in the central nervous organs in human cases of poliomyelitis correspond
      to those that arise from the intraneural method of infection in the monkey. The
      virus in transit from the blood through the cerebrospinal fluid to the substance
      of the spinal cord and brain is capable of being neutralized by intraspinous
      injection of immune serum, whereby the production of paralysis is averted. Carmin
      in a sterile and finely divided state introduced into the meninges and ventricles
      sets up an aseptic inflammation, but is quickly taken up by cells, including
      ependymal cells. When an aseptic inflammation has been previously established by
      means of horse serum, or when the nervous tissues are already injured by the
      poliomyelitic virus, the pigment appears to enter the ependymal cells more
      freely. The experiments described support the view that infection in epidemic
      poliomyelitis in man is local and neural, and by way of the lymphatics, and not
      general and by way of the blood. Hence they uphold the belief that the infection
      atrium is the upper respiratory mucous membrane.

PMID- 19867820
TI  - EXPERIMENTAL TUBERCULOSIS OF THE CORNEA.

PMID- 19867821
TI  - THE EXCRETION OF NITROGEN IN FEVER.
AB  - The rise of temperature following typhoid vaccination is accompanied by a marked
      increase in the output of total nitrogen, creatinin, and especially of uric acid.
      The reaction to tuberculin is slower, but is also accompanied by an increased
      output of nitrogenous substances, that is, however, less uniform and generally
      less pronounced. In a case of malaria there was a tendency for the rise of
      temperature to be accompanied by an increased output of total nitrogen and less
      uniformly of creatinin; on two days on which the fever was preceded by rigor the
      output of uric acid was increased.

PMID- 19867822
TI  - LIVER FUNCTION AS INFLUENCED BY THE DUCTLESS GLANDS.
AB  - When phenoltetrachlorphthalein is injected intravenously, it is eliminated from
      the body in the bile through the activity of the hepatic epithelium. The feces
      may be collected after purgation and the phthalein extracted and estimated
      against a standard solution. The estimation of phthalein can be done with
      accuracy in a suitable colorimeter and the elimination in normal dogs is quite
      constant. Given a definite liver injury by means of poisons (chloroform,
      phosphorus), the amount of phthalein excreted will be diminished and the fall in
      output will be proportional to the amount of injury. With an acute fatal
      poisoning the curve may fall to zero. Under certain conditions of vascular
      interference the liver phthalein may show a decreased output; in passive
      congestion of the liver and with the Eck fistula the liver output may fall
      considerably below normal. Known disturbances of the liver function due to
      parenchymatous injury or vascular disturbances are indicated by a fall in the
      phthalein. excretion curve. Conversely it may be claimed that a drop in phthalein
      excretion may indicate a decrease in the functional capacity of the liver even if
      there be no detectable histological changes. Adrenal insufficiency produced by
      extirpation of three fourths or more of the gland tissue will be associated with
      a drop in liver phthalein excretion. With hypertrophy of the adrenal fragment the
      excretion comes back to normal, but may fall again when more adrenal tissue is
      removed (text-figure 1). Pancreatic insufficiency causes a progressive fall in
      the phthalein excretion indicating a grave lowering of the functional capacity of
      the liver (text-figure 2). This fact has a direct bearing on the question of
      diabetes. Parathyroid insufficiency with tetany causes no decrease in phthalein
      output, but at times a rise above normal. This comes out best when the phthalein
      curve is low following pancreas extirpation. Parathyroid tetany may cause
      hyperactivity on the part of the liver cells. Thyroid insufficiency produces no
      change in the uniform curve of phthalein excretion. Hypophysis insufficiency
      shows an initial fall in the curve, followed by a return to normal and a final
      drop in the last few days before death. These experiments supply evidence to the
      effect that the liver is very much concerned in the derangement that follows the
      removal of the ductless glands. Hence it seems probable that this disturbance of
      the liver function may be an important factor in the general symptom complex of
      ductless gland insufficiency. In conclusion we wish to express our appreciation
      to Dr. S. J. Crowe and Dr. A. P. Jones for assistance rendered in performing some
      of the operations for gland removal.

PMID- 19867823
TI  - THE RELATION OF BACTERIOLYSIS TO PROTEOLYSIS : STUDIES ON FERMENT ACTION. XVI.
AB  - 1. There is no demonstrable increase in non-coagulable nitrogen during
      bacteriolysis. 2. Bacteria treated with immune serum and complement are so
      altered that they are more readily digested by trypsin. 3. Bacteria treated with
      complement alone become more resistant to proteolysis. 4. Bacteria treated with
      an excess of immune serum and complement become more resistant to proteolysis.

PMID- 19867824
TI  - STUDIES ON THE CHEMISTRY OF SEROUS EFFUSIONS.
AB  - A comparison of the results obtained in the analysis of the different effusions
      shows that they vary, (1) according to location, and (2) according to the disease
      in which they are produced. Thus the subcutaneous effusions are totally different
      in their composition from the abdominal or pleuritic fluids; and again the
      abdominal fluid of nephritic origin is different from those of cardiac or other
      origin. The cutaneous effusions are characterized by a very low protein content
      and a small amount of incoagulable nitrogen. Of the protein present in these
      fluids, the globulin constitutes the greater portion. In the mixed
      cardionephritic fluids the ratio of globulin to albumin is lower than that in
      normal blood serum; but when compared with the blood sera of cardionephritic
      cases there appears to be a certain parallelism. The chloride content of these
      fluids is considerably above that found in normal blood serum, but is comparable
      with those of corresponding cases. The effusions occurring in serous cavities
      differ from the cutaneous ones by their higher protein content. The highest
      values are attained in the pleural fluids, in which the protein present is almost
      the same as that in normal blood serum. The incoagulable nitrogen in these fluids
      is uniformly low. The chlorides vary in amount according to the nature of the
      case. In the effusions of inflammatory origin the values are lower than those
      found in the blood. In the pleural fluids of other than inflammatory origin the
      chloride content is either the same or higher than that of blood serum. The
      globulin-albumin ratio in all of these fluids except one (table III, fluid 61) is
      higher than that of normal blood serum. Otherwise the highest value is presented
      by a pleural fluid from a case of nephritis (table III, fluid 205) and the lowest
      by an empyema fluid (table III, fluid 30). The latter case is of especial
      interest because of the theory, first propounded by Schmidt, that the leucocytes
      in the purulent fluid are largely responsible for high globulin content. The
      abdominal fluids in general are less rich in protein than the pleural effusions.
      Those of cardiac origin give the highest protein values, but the globulin-albumin
      ratios are lower than in the pleural fluids or in the blood sera of corresponding
      cases. Only in two fluids does the globulin reach a percentage of 62 and 52.2. In
      both these cases the chloride content is also high. The incoagulable nitrogen in
      all of them is rather low. In one fluid of purely nephritic origin the protein
      content is low and all of it is globulin. This is suggestive, when compared with
      the values obtained in the analysis of the blood sera from nephritic cases. The
      results obtained in the analysis of abdominal fluids from cardionephritic cases
      approach very closely those obtained in purely cardiac cases.

PMID- 19867825
TI  - PNEUMOCOCCUS HEMOTOXIN.
AB  - Solutions of the bodies of pneumococci, obtained by dissolving them in dilute
      solutions of sodium cholate, by permitting them to undergo autolysis, or by first
      freezing, drying, and then grinding in salt solution, are actively hemolytic for
      rabbit, sheep, guinea pig, and human red blood corpuscles. The substance on which
      this hemolytic property depends is very labile, much of its activity is lost on
      passing through a filter, and it is destroyed by the action of trypsin. In its
      properties it corresponds to the substance contained in such solutions which
      causes the death of guinea pigs on intravenous injection. Its activity is
      prevented by the presence of minute amounts of cholesterin. Following the
      injection of this solution into rabbits and sheep, the sera of these animals
      acquire increased power of inhibiting its hemolytic action. It therefore
      possesses antigenic properties. It may therefore be concluded that the bodies of
      pneumococci contain a toxin that is hemolytic for red blood corpuscles. This
      substance is not simply a product of autolysis but undoubtedly exists preformed
      in the bacterial cell. However, it is not given up to the surrounding fluid as
      long as the bodies of the bacteria are intact. It may therefore be considered a
      hemolytic endotoxin.

PMID- 19867827
TI  - THE ROLE OF THE SPLEEN IN BLOOD FORMATION.

PMID- 19867826
TI  - THE PRODUCTION OF METHEMOGLOBIN BY PNEUMOCOCCI.
AB  - 1. Pneumococci in contact with hemoglobin transform this into methemoglobin. This
      reaction occurs only when the pneumococci are living; it is not induced by the
      culture fluid or by extracts of the bacteria. 2. The reaction does not occur when
      hemoglobin is added to an emulsion of washed pneumococci in salt solution.
      However, if minute traces of dextrose be added to such a mixture, the reaction
      quickly occurs. The dextrose may be replaced by any one of a number of other
      sugars, and also by certain other organic substances, if the latter are added in
      large amounts. Certain other organic substances are not able to replace dextrose,
      but it has been impossible to determine any special molecular configuration on
      which this property depends. 3. The formation of methemoglobin by pneumococci
      probably resembles the formation of methemoglobin by certain chemical substances,
      such as aminophenol. 4. From the work of others it is probable that the formation
      of methemoglobin is always a reaction of oxidation. In the formation of
      methemoglobin by reducing agents, the latter are first oxidized, this occurring
      better in the presence of oxyhemoglobin. In certain instances an alternate
      oxidative and reduction of the transforming agent occurs, so that the reaction is
      continuous. The effect which the presence or absence of free oxygen has on the
      reaction with pneumococci suggests that this follows similar lines. 5. The
      reaction does not occur in the absence of oxygen. If the free oxygen be first
      removed, and then replaced, the reaction occurs more rapidly than if the oxygen
      had not been removed. The presence of free oxygen in excess slightly delays the
      reaction, possibly because of the inhibition of the reduction process which forms
      the first part of the reaction. 6. The explanation of this phenomenon of
      methemoglobin production is not only of importance so far as this special
      reaction is concerned, but also because it suggests an explanation for the manner
      in which pathological effects are produced by those bacteria which apparently
      produce no soluble toxin.

PMID- 19867828
TI  - ON THE IMMUNIZATION OF ANIMALS WITH BACTERIAL PROTEOTOXINS (ANAPHYLATOXINS).
AB  - Our experiments have shown definitely that guinea pigs, once injected with
      sublethal doses of bacterial proteotoxins (anaphylatoxins), acquire distinct
      tolerance to these poisons. The degree to which such resistance or tolerance is
      developed is never very high, in no case in our experiments exceeding the ability
      to withstand one and one half to twice the fatal dose of the poisons. During the
      three or four days immediately following the first injection the animals appear
      to be slightly less resistant than are normal controls, this depending probably
      upon the in jury done by the administered poison. Tolerance begins to be evident
      after from four to seven days, seems to be most highly developed in about two
      weeks, but lasts in a diminishing degree for at least as long as sixty days. Our
      experience, in this respect, with the poisons resulting from the contact of
      active serum and bacteria is similar to that of Vaughan with the toxic protein
      split products obtained by chemical methods. The development of increased
      resistance definitely established, the questions immediately arise: (1) Is this
      tolerance specific? And (2) can it be passively transferred, with the serum, to a
      normal animal? We have begun to seek answers for these problems but as yet our
      data are too meager to permit definite conclusions. The significance of the
      existence of higher resistance in animals treated with proteotoxins is far
      reaching both in connection with anaphylaxis and with immunity in general. We are
      not inclined to attribute to it as predominant a part in anti-anaphylaxis as is
      assigned to it by Bessau. For, in the first place, tolerance to the poisons is
      never developed to a very high degree, and, moreover, it does not become evident
      until three or four days after the first injection, while anti-anaphylaxis
      develops almost immediately after shock. However, there seems to us to be strong
      presumptive evidence that such tolerance to the poisons may play an important
      and, possibly, a non-specific part in anti-anaphylaxis, the chief underlying and
      specific cause of this phenomenon being the exhaustion of antibodies, or
      desensitization in the sense of Besredka. The relation of such tolerance to the
      resistance of the animal to bacterial infection is, of course, obvious if we
      accept the possibility of the production of such poisons in the injected body and
      their participation in the production of bacterial toxemia. We hope to throw more
      light on these relations in another paper dealing with the aggressin-like
      properties of the proteotoxins.

PMID- 19867829
TI  - EXPERIMENTS ON THE ROLE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL
      TUBERCULOSIS IN MICE.
AB  - Mice either normal or splenectomized after exposure to X-ray are markedly more
      susceptible to bovine tuberculosis than are normal animals. Animals
      splenectomized a short time prior to inoculation are also more susceptible than
      normal, while those splenectomized eight to ten days before inoculation have
      about the same resistance as normal. The mice splenectomized three to four weeks
      before inoculation have a resistance increased over the normal, as has already
      been shown by Lewis and Margot. As X-ray in the doses used apparently affects
      only the lymphoid tissue and as the hypertrophy of the remaining lymphoid tissue
      after splenectomy is so rapid that the circulating lymphocytes may be much above
      the normal by the third week, it is concluded that this evidence, taken with the
      well known association of the lymphocytes with tuberculous lesions, points
      strongly to the lymphocyte as an important agent in the defensive mechanism
      against tuberculosis.

PMID- 19867830
TI  - ON THE CAUSE OF THE LOCALIZATION OF SECONDARY TUMORS AT POINTS OF INJURY.
AB  - The cause of the frequent localization of secondary tumors at points of injury is
      not known. Our work deals with this problem. For the experiments the peritoneal
      cavity has been employed as offering relatively uncomplicated conditions, and the
      fate of mouse tumor brought into contact with a peritoneal lining injured in
      various ways has been studied. The injection of a suspension of mouse tumor into
      a healthy peritoneal cavity has little success as a rule compared with a similar
      injection into the subcutaneous tissue. We have found that the resistance of the
      peritoneal lining thus indicated can be largely if not completely abolished by
      the preliminary injection of a mechanical irritant (Kieselguhr, lycopodium). That
      the change thus brought about is independent of general immunity phenomena is
      shown by the fact that a local injury renders susceptible the part of the
      peritoneum immediately affected and that part only. Special tests show that the
      factor important in rendering the peritoneum more susceptible is the injury to
      the subendothelial connective tissue. Susceptibility persists after the
      endothelium has regenerated over the reacting connective tissue. Schmidt has
      found that the cells of tumor emboli in the pulmonary arterioles are able to
      penetrate the endothelium of the vessel only after they have been provided with a
      stroma from the subendothelial connective tissue. Our findings are easily
      explained on the basis thus suggested. A connective tissue highly cellular and
      perhaps still proliferating as the result of injury may well elaborate the stroma
      for a tumor more rapidly than normal connective tissue. Tests of growth in vitro
      support this idea. Connective tissue reacting to an injury grows profusely and
      almost immediately when incubated in plasma, whereas normal tissue from the same
      region shows usually no growth whatever. Dead tumor fragments in contact with the
      peritoneum cause a change favorable to the lodgment and growth of later tumor
      fragments. It seems not improbable that the peritoneal dissemination of certain
      human neoplasms may be accomplished indirectly through the death of the first
      tumor fragments cast off. Our observations have been purposely confined to the
      effects of injury on the peritoneal lining ; but they seem to afford the basis
      for a generalization. The secondary localization of tumors at points of injury
      may be attributed with good reason to the presence at such points of an active
      connective tissue capable of elaborating a stroma rapidly and abundantly. For it
      is the proliferation of the subendothelial connective tissue to form a supporting
      stroma that determines the fate of free tumor cells, whether these lie on the
      peritoneum or within a vessel.

PMID- 19867831
TI  - ON THE GREATER SUSCEPTIBILITY OF AN ALIEN VARIETY OF HOST TO AN AVIAN TUMOR.
AB  - A transplantable sarcoma of the fowl, known as Chicken Tumor XVIII, in our
      series, succeeds better in chickens of an alien breed (Plymouth Rock) than in
      those of the variety in which it originated (brown Leghorn). This is not due to
      gross physical differences in the two breeds but to some more subtle factor and
      one which perhaps acts by influencing the agent causing the tumor. It would seem
      that Chicken Tumor XVIII, as it occurred in nature, was an instance of a disease
      appearing spontaneously in an animal of relatively insusceptible variety.

PMID- 19867832
TI  - ON IMMUNITY TO TRANSPLANTABLE CHICKEN TUMORS.
AB  - The phenomena of natural and acquired resistance to transplanted chicken tumors
      strikingly resemble those observed in the case of transplanted mammalian growths;
      and no more than those do they suggest that the tumors have an extrinsic cause.
      That there may exist in fowls implanted with a chicken tumor a resistance
      directed against the tumor-causing agent distinct from the resistance manifested
      against the alien tumor cells has been shown in a previous article. Both sorts of
      resistance are present in a fowl in which a tumor has retrogressed, the
      resistance in such an instance being acquired. That directed against the agent is
      largely specific, giving little if any protection against the agents causing
      other tumors. There is some evidence that the conditions upon which a fowl's
      natural resistance depends are the same for the agents causing different chicken
      tumors. It has proved impossible to protect chickens against the agent causing
      the simple sarcoma by injecting them with dried tumor material in which this
      agent has been attenuated by heat. The transfer of blood from resistant fowls to
      fowls with growing tumors is in our experience void of effect on the tumors.

PMID- 19867833
TI  - THE INFLUENCE OF DIET ON TRANSPLANTED AND SPONTANEOUS MOUSE TUMORS.
AB  - Previous work has shown that the growth of grafts of transplantable tumors can be
      in many cases prevented or retarded by underfeeding the new host or by putting it
      on a special diet. The effect of such treatment on large tumors has been little
      studied; and the effect on metastases and recurrences has not been studied at
      all. Apart from certain clinical observations nothing is known as to the
      influence on spontaneous tumors of alterations in the diet. Experiments with
      transplanted rat and mouse tumors along the lines thus suggested show that large
      growths of certain strains are checked in their development by underfeeding the
      host upon a special diet (Sweet's modification of one of Mendel and Osborne's
      foods) or in some cases by simple underfeeding. Two metastasizing mouse tumors
      are instances in point. They stopped growing or grew very slowly in hosts
      underfed on the special diet. The Flexner-Jobling rat carcinoma, on the other
      hand, was unaffected by the most rigorous underfeeding on a mixed diet when this
      was begun after the tumor had been growing for a short period. Experiments to
      test the influence of underfeeding upon recurrences of this tumor gave results
      that varied from series to series of animals. The findings strongly indicate that
      generalizations from work with transplanted tumors as regards the effects of diet
      on spontaneous growths are unwarranted. By underfeeding on Sweet's food mice with
      spontaneous tumors, beginning some days prior to operation, it has proved
      possible in most cases to delay for a relatively long period the development of
      recurrences and the growth of tumor bits (grafts) disseminated at the time of
      surgical interference. The treatment entailed great loss of weight. Tumor mice
      kept on ordinary diet previous to operation, but put thereafter on an abundant
      ration of Sweet's food, developed recurrences as early as the tumor mice on
      ordinary diet; whereas the growth of auto-implants was, relatively speaking, much
      delayed. These results seem attributable rather to a gradual malnutrition induced
      by the special food than to the circumstance that it lacked a growth principle.
      In none of the dieted mice was a definite cure obtained. Ordinarily a recurrence
      appeared and the grafts began to grow soon after the host, again on ordinary
      food, had regained weight. A few spontaneous tumors seem absolutely unaffected by
      the most rigorous dieting. Wounds heal with marked slowness in animals that have
      become thin as a result of dieting, and an inert foreign body (agar-agar)
      injected subcutaneously is very slowly encapsulated and organized. In these facts
      may be found a suggestion as to the method whereby dieting delays tumor growth.
      For it may well be that, with a lessened proliferative activity of the host
      tissue, the elaboration of a vascularizing and supporting stroma such as most
      tumors depend upon for their growth, at least indirectly, is much delayed. The
      rapid growth of tumors in emaciating individuals is not incompatible with the
      present findings. Such growth may be consequent upon a selection in the host of
      those cells most fit to cope with the increasingly difficult nutritive
      conditions. But experiments designed to demonstrate this have been unsuccessful.
      It is conceivable that recurrences of certain human tumors and the development of
      metastases may be delayed or prevented for a period by methods somewhat similar
      to those employed against spontaneous mouse tumors in the present investigation.
      But generally speaking only the more malignant human tumors would require such
      palliative measures, and these are precisely the ones that would prove,-if
      experience with mice is an index,-least amenable to alterations in the nutrition
      of the host.

PMID- 19867834
TI  - BACTERIAL ANTIFERMENTS : STUDIES ON FERMENT ACTION. XVII.
AB  - 1. Intact bacteria probably resist tryptic digestion because of the absence of an
      exposed protein substrate. 2. Dried organisms resist digestion in a degree
      proportional to their content of unsaturated lipoids. 3. Lipoidal extractives
      reduce the resistance to tryptic digestion. 4. The extracted lipoids (saponified)
      are antitryptic in a degree proportional to their unsaturation. 5. The
      inactivation of the antiferment in Gram-negative organisms is probably due to
      changes in the degree of lipoidal dispersion. 6. Bacteria adsorb lipoids from the
      serum when incubated at 37 degrees C. Such organisms when dried are found to be
      more resistant to tryptic digestion than untreated organisms.

PMID- 19867835
TI  - LIPOIDS AS INHIBITORS OF ANAPHYLACTIC SHOCK : STUDIES ON FERMENT ACTION. XVIII.
AB  - 1. The antitryptic titer of the serum can be increased by subcutaneous injections
      of serum lipoids (antitrypsin) and of the lipoids from egg yolk. 2. Animals so
      injected show a relative immunity to acute anaphylactic shock (two minimum lethal
      doses). 3. Extraction of lipoids contained in antigens increases the toxicity of
      the antigen when injected into a sensitized animal. 4. Sublethal doses of soap
      solutions injected simultaneously with the antigen (purified horse serum albumen)
      prevent anaphylactic shock. 5. The refractory state following anaphylactic shock
      is related in part to an increase in the antitryptic titer of the serum.

PMID- 19867836
TI  - FURTHER EXPERIMENTS UPON THE EFFECTS OF EXTIRPATION OF THE THYMUS IN RATS, WITH
      SPECIAL REFERENCE TO THE ALLEGED PRODUCTION OF RACHITIC LESIONS.
AB  - Rachitic changes in the bones and teeth occur in young albino rats as the result
      of spontaneous disease, possibly of infective origin. This disease is often, but
      not always, accompanied by an arrest of growth and malnutrition. There is no
      valid reason for attributing such lesions to the loss of thymic function. In some
      of the rats showing the disease, an unusual number of mitoses were found in the
      parathyroid glands, but no evidence of injury to these structures. It has not
      been found possible to confirm the statements of Klose and Magnini as to the
      fatal effects of complete thymus extirpation in rats.

PMID- 19867837
TI  - THE CALCIUM CONTENT IN BONES AND TEETH FROM NORMAL AND THYMECTOMIZED ALBINO RATS.

PMID- 19867838
TI  - THE INFLUENCE OF VARIOUS SUBSTANCES ON THE GROWTH OF MOUSE CARCINOMA.
AB  - We have described the methods used in determining the influence of certain
      substances on tumor growth, and we measured approximately the degree of
      reliability of the quantitative method used. We examined with these methods
      various classes of substances,- distilled water, a number of inorganic salts,
      inorganic colloidal substances, various organic colloidal and non-colloidal
      substances, especially various proteids, tuberculin and hirudin alone as well as
      in combination with other substances. Distilled water, various inorganic sulphur
      preparations, and various inorganic salts did not show an inhibiting effect on
      tumor growth sufficient to be detected by means of our first method. Only in the
      case of gold potassium cyanide was there possibly a slightly retarding influence
      present. On the other hand, certain colloidal solutions of heavy metals (copper,
      platinum, gold) retard the growth of a number of tumors of injected animals.
      Certain combinations of copper salts and casein act in a similar manner. Of the
      organic substances used, casein, nucleoproteid, and hirudin were active, while
      the other proteids tested, as well as various other organic substances and
      tuberculin and lecithin, seemed to be either without effect or weaker than the
      other substances mentioned as retarding the tumor growth. Hirudin was active and
      caused in addition to its inhibiting influence the retrogression of a certain
      number of tumors. Especially active was a combination of hirudin with colloidal
      copper and of hirudin with nucleoproteid. One single injection of casein or
      nucleoproteid, or of the Heyden preparation of colloidal copper, leads to a more
      or less marked edematous condition of a certain number of tumors, while hirudin
      caused in addition, in many cases, marked hemorrhages in or around the tumors.
      Other substances which we tested did not show this effect, although their
      inhibiting action on tumor growth may have been equally strong. Very young tumors
      (two to six days old) are not retarded in their growth through injection of
      colloidal copper or hirudin, while nine to thirteen days old tumors are,
      independently of their size on the ninth day, inhibited in approximately the same
      relative degree; absolutely, however, the more rapidly growing smaller tumors are
      more markedly inhibited than the normally more slowly growing larger tumors.

PMID- 19867839
TI  - IMMUNIZATION AGAINST THE ACTION OF SUBSTANCES INHIBITING TUMOR GROWTH.
AB  - 1. Through a set of preliminary injections of colloidal copper or hirudin, given
      from the second to the sixth day after transplantation, we can weaken the effect
      of injections of the same substances given from the ninth to the thirteenth day
      after transplantation. 2. Injections of colloidal copper given before the
      transplantation of the tumor lead to a weakening of the effect of injections
      given from the ninth to the thirteenth day after transplantation. 3. The same
      result can be obtained if we inject colloidal copper or hirudin into mice from
      the second to the sixth and from the ninth to the thirteenth day after
      transplantation, and use these tumors at the end of the series of injections for
      further transplantation into another set of mice; the developing tumors are more
      resistant to the action of colloidal copper or hirudin than new control tumors.
      4. We may therefore conclude that the immunity has two sources: (a) it is based
      on changes taking place somewhere in the host organism; and (b) it is localized
      in the tumor cells themselves which transfer this immunity to the following
      generations of tumor cells. 5. The immunity acquired against colloidal copper
      does not protect noticeably against the action of hirudin, and vice versa. The
      immunity is therefore specific. 6. We discuss certain general conclusions which
      may be drawn from these experiments. We expect to test the validity of these
      results in further experiments.

PMID- 19867840
TI  - DO SUBSTANCES INHIBITING TUMOR GROWTH EXERT A RETARDING INFLUENCE ON THE
      REGENERATION OF THE SKIN?
AB  - Repeated injections of colloidal copper, hirudin, nucleoprotein, and casein,
      which have a definite retarding influence on tumor growth, given to mice during
      the process of wound healing do not produce any noticeable influence on the
      course of regeneration.

PMID- 19867841
TI  - THE EFFECT OF GENTIAN VIOLET ON PROTOZOA AND ON TISSUES GROWING IN VITRO, WITH
      ESPECIAL REFERENCE TO THE NUCLEUS.
AB  - 1. Gentian violet may be regarded as a true vital nuclear stain. 2. Embryonic and
      adult tissue of the frog will grow in vitro in the presence of gentian violet of
      a far stronger dilution than that necessary to kill many bacteria. In these
      experiments, for example, successful tissue growths were obtained when gentian
      violet 1 to 20,000 was used, yet Bacillus subtilis will not grow in 1 to 100,000
      dilution and grows very badly in 1 to 1,000,000 dilution. This fact may simplify
      the technique of the growth of certain tissues by eliminating the risk of
      bacterial contamination. 3. The use of stains in the plasma in which tissue is
      grown will probably facilitate the study of nuclear growth. 4. Gentian violet
      appears to have a certain selective action on tissue similar to that exercised by
      the dye on bacteria. Certain observations made last year in this laboratory (too
      few to serve as more than a suggestion) seem to indicate that another dye
      (methylene blue) acted as a stimulant to the growth of connective tissue. These
      leads should be followed out and the effect of various stains studied in the hope
      of discovering dyes which will exercise a sharp selective action on growing
      tissue. 5. The growth of animal cells in a strength of dye much more than
      sufficient to kill many pathogenic organisms lends encouragement to efforts now
      being made in this laboratory to apply the observations on the bactericidal
      effect of gentian violet and allied stains to the treatment of disease. Moreover,
      the ability of growing cells to rid themselves of this dye would indicate that it
      may be possible to apply the dye to infected tissue and count on the cells to
      eliminate the material after its work had been done.

PMID- 19867842
TI  - THE EFFECT OF VARIOUS TISSUE EXTRACTS UPON THE GROWTH OF ADULT MAMMALIAN CELLS IN
      VITRO.
AB  - The cultivation of cells in vitro affords a valuable means of estimating the
      effects of tissue extracts. Tissue extracts have a definite effect upon the
      growth of adult mammalian cells in vitro. The majority of tissue extracts
      stimulate the growth of connective tissue, but liver extract inhibits it. The
      extracts are to a certain extent specific in their action upon the growth of
      parenchymatous cells. Some cells are stimulated by one extract and inhibited by
      another, and those extracts which inhibit one type of parenchymatous cell may
      stimulate another type. Homogenous and autogenous extracts are equally
      efficacious in their action upon the growth of cells. The extracts may be
      preserved for a short period of time without suffering any change in their power
      of affecting the growth of cells.

PMID- 19867843
TI  - OBSERVATIONS ON EXPERIMENTAL TYPHOID INFECTION OF THE GALL BLADDER IN THE RABBIT.
AB  - 1. Besredka's living sensitized vaccine, given intravenously, does not produce a
      typhoid lesion of the gall bladder in the rabbit. 2. The first transplant of this
      vaccine is capable of producing this lesion. Hence this vaccine is not entirely
      safe to handle. 3. Regular infections of the gall bladder have not been produced
      by carrying a known pathogenic strain on rabbit blood agar, by successive passage
      through animals, or by the use of freshly isolated strains. 4. No evidence could
      be demonstrated in the rabbit of the immunity produced in man by vaccination with
      a whole killed vaccine. 5. Vaccine treatment did not cure the gall bladder
      lesion. 6. With the present methods of producing infections in the chimpanzee and
      the rabbit, neither of these animals is suitable for deciding the problems of the
      immunization of man by vaccines. These problems must be settled, as some of them
      already have been settled, by actual experience with large numbers of men kept
      under close observation.

PMID- 19867844
TI  - PROTEOTOXINS (ANAPHYLATOXINS) AND VIRULENCE.
AB  - 1. Our experiments show that proteotoxin (anaphylatoxin) produced with typhoid
      bacilli and active guinea pig serum, by the general method of Friedberger,
      possesses aggressin-like action in that, when injected together with sublethal
      doses of bacteria, it renders them lethal. 2. This action is not specific, since
      even when typhoid bacilli are used in its production, the proteotoxin possesses
      this property not only for typhoid bacilli, but for staphylococci and prodigiosus
      bacilli, the only other organisms with which we worked. 3. This action is
      manifest in the experiment only when quantities of proteotoxin are used which can
      produce a certain degree of systemic poisoning. 4. It is not due to anti-opsonic
      action since the phagocytosis of staphylococci in the presence of active serum
      takes place readily in spite of the presence of relatively considerable amounts
      of the poison. 5. The aggressin-like action of the proteotoxin is probably due to
      the leucopenia that it causes. It is not likely that this leucopenia is dependent
      upon a negative chemotactic action, in the ordinary sense of this term, but it is
      probably due to the general intoxication of the animal, resulting among other
      things in the poisoning of those tissue elements which ordinarily react to
      infection with the mobilization of leucocytes in the circulation. It has seemed
      to us that the results of our experiments were of interest also in throwing some
      light on the general problem of virulence. The thought naturally suggests itself
      that Bail's so called aggressins were nothing more or less than proteotoxins, or
      anaphylatoxin. It has been shown by Friedberger and Nathan (3) that poisons of
      this description may be formed in the peritoneal cavities of animals, and if we
      examine the method by which Bail (4) prepared his aggressive exudates, it seems
      likely that they contained proteotoxins. Moreover, although Bail's aggressins are
      described as non-toxic in themselves, this is a discrepancy to which, it seems to
      us, no great weight need be attached in this connection, since the poisonous
      properties of the proteotoxins are clearly apparent only when considerable
      amounts, two to three cubic centimeters, are intravenously injected into young
      guinea pigs, and below this quantity a threshold is rapidly reached beyond which
      no visible reaction whatever is achieved. We have not yet, it is true, shown that
      animals may be immunized against bacterial infection by treatment with the
      proteotoxins, a result obtained by Bail with his aggressins. But we feel that the
      mere fact that tolerance to proteotoxin may be established, a phenomenon which
      has been the subject of an earlier paper, is a step in this direction. Further
      than this the analogy cannot be carried since we do not know as yet whether the
      proteotoxin tolerance is specific,-a fact which would be necessary in order to
      identify completely these substances with the substances studied by Bail. In
      view, however, of the many objections that have been voiced against this phase of
      Bail's work, and of the fact that a rapid accumulation of leucocytes is described
      as characteristic of aggressin immunity, it seems not unlikely that even in this
      aspect of the problem aggressin and proteotoxin may eventually be identified. It
      is probable, also, if we reason logically from the premises which our experiments
      supply, that the power of invasion of many microorganisms is intimately related
      to their ability to react with the active blood constituents of the infected
      animal. This has already been suggested in the work of Embleton and Thiele (5).
      If, indeed, the condition of bacterial anaphylaxis or hypersusceptibility depends
      upon the establishment of a balance between the injected bacterial antigen and
      the blood constituents, such that proteotoxins are formed, a supposition rendered
      probable by much recent work, then our experiments would tend to show that
      bacterial anaphylaxis implies, at the same time, a condition of lessened
      resistance to invasion by the bacteria (6). It may even be that generalized
      invasion, after localization, must await the striking of such a balance, an
      interval which, in the case of diseases like typhoid fever, may form a part of
      the incubation time. At the same time, in such diseases, the action of the
      proteotoxin would explain the leucopenia that accompanies the bacterial invasion.
      We do not, of course, expect to explain virulence in general by these phenomena.
      In the case of organisms like the pyogenic cocci, the pneumococcus, and some
      other bacteria, there is apparently another important element contributed in the
      resistance of the invader to direct reaction with the active serum constituents.
      In many of these organisms the slight extent or absence of serum lysis or even
      bactericidal action would point in this direction, and here the appearance of
      proteotoxin would be secondary in importance or possibly absent entirely until
      late in severe infections. The non-specificity of the aggressive action of
      proteotoxin goes far toward explaining the increased susceptibility to other,
      secondary infections apparent during the course of many cases of typhoid fever
      and in some other diseases. It should also have an important bearing on our
      understanding of mixed infections.

PMID- 19867845
TI  - A METHOD OF COUNTING THE ACTUAL NUMBER OF PURKINJE CELLS PRESENT IN A GIVEN AREA
      OF CEREBELLUM, AND ITS APPLICATION IN TEN CLINICAL CASES.
AB  - 1. This method of determining the actual number of Purkinje cells present in a
      given area of cerebellum is practicable and of sufficient accuracy to make it
      another useful means of studying nerve cell activity. 2. In its application to
      clinical cases it is found that increasing nerve cell exhaustion is accompanied
      by increasing nerve cell disappearance, although it is recognized that
      theoretically complete nerve cell exhaustion could be present without nerve cell
      disappearance on account of the individual dying before phagocytic action could
      take place. 3. This disappearance of nerve cells corroborates the theories and
      observations made on phagocytosis of nerve cells, inasmuch as it shows that nerve
      cells disappear from the brain. 4. While there are too few cases to establish a
      normal actual Purkinje cell count, it is of interest to note that there were 16.6
      per cent. fewer cells in the case with the maximum cell exhaustion (57 per cent.)
      than in the case of the normal man (2 per cent.).

PMID- 19867846
TI  - AGGLUTINATION PHENOMENA IN LOBAR PNEUMONIA.
AB  - 1. Agglutinins are present in the blood of patients suffering from lobar
      pneumonia during some stage of the disease in a large percentage (73.8 per cent.)
      of the cases due to pneumococci belonging in groups I, II, and IV. 2. In most
      very severe and fatal cases agglutinins cannot be demonstrated, and it is
      probable that their absence during the later days of the disease may have
      unfavorable prognostic significance. 3. No agglutinins are demonstrable by the
      technique employed in the blood of patients suffering from infection with
      Pneumococcus mucosus (group III). 4. In certain cases agglutinins may be
      demonstrable for only one day, and in other cases they may persist for several
      weeks. 5. When agglutinins are demonstrable they usually appear at about the time
      of the crisis. 6. It has not been possible to demonstrate that treatment with
      immune serum has any effect on the appearance of agglutinins. 7. The agglutinins
      present in cases due to organisms of types I and II are always specific for the
      type of organism causing the infection. In certain cases the agglutination
      reaction may be more active or appear earlier when the homologous organism is
      employed than when other organisms of the group are used in the test. In cases
      due to organisms of type IV, the serum never causes agglutination of any organism
      except the homologous one.

PMID- 19867847
TI  - CULTIVATION OF THE SKIN EPITHELIUM OF THE ADULT FROG, RANA PIPIENS.
AB  - 1. Fragments of skin taken from the back of the leopard frog were cultivated in a
      mixture of plasma and muscle extract of the same species. 2. A few hours after
      explanation, processes of activity are seen to arise, which finally lead to the
      formation of a compact epithelial rim around the fragment of skin. 3. These
      epithelial cells undergo gradual transformation into a spindle-shaped type of
      cell; in this form they resemble the spindle cells which have been described as
      connective tissue cells. 4. The growth of a rim of tissue around the explanted
      fragments of skin may be ascribed principally to the activity of a basal layer of
      epithelial cells, the units of which first advance into the medium as compact
      membranes by means of the so called epithelial movement, but which later become
      separated from the compact membrane, and having assume a spindle form, spread
      according to the manner of connective tissue cells. 5. In contradistinction to
      this basal layer, the cells of an upper and middle layer of epithelium upon
      separation from the fragment of skin and isolation in the nutritive medium,
      remain completely inactive. 6. The connective tissue of frog skin, for reasons
      not yet completely established, does not participate in the production of the rim
      of cells, possibly for the reason that it was early surrounded by the epithelium
      and was thus prevented from sending out cells into the medium. 7. The
      transformation of the epithelial cells into a type of cells of the spindle form
      is a result of the changes in the physicochemical conditions brought about by the
      life in vitro, which become similar to the physicochemical conditions normally
      characteristic of connective tissue. 8. The final stage of the explanted
      fragments of skin is a hollow epithelial sphere (cystic stage) filled with
      connective tissue. 9. During the cystic stage the epithelium again shows its
      normal polar differentiation, as a consequence of the physicochemical conditions
      which now approach normal. 10. These conditions also permit of the shedding of
      cells in a vertical direction, although previously the production of cells in a
      horizontal direction had already become impossible.

PMID- 19867848
TI  - THE INFLUENCE OF DIET UPON NECROSIS CAUSED BY HEPATIC AND RENAL POISONS : PART I.
      DIET AND THE HEPATIC LESIONS OF CHLOROFORM, PHOSPHORUS, OR, ALCOHOL.

PMID- 19867849
TI  - THE INFLUENCE OF DIET UPON NECROSIS CAUSED BY HEPATIC AND RENAL POISONS : PART
      II. DIET AND THE NEPHRITIS CAUSED BY POTASSIUM CHROMATE, URANIUM NITRATE, OR
      CHLOROFORM.
AB  - Diet exerts a profound influence upon the toxicity (tested in the omnivorous
      white rat) of certain substances, namely, chloroform, phosphorus, potassium
      chromate, and uranium nitrate, which cause necrosis of the parenchymatous cells
      of the liver or of the kidney. Susceptibility to intoxication with all of these
      substances is less after a diet rich in carbohydrate than after a diet consisting
      of meat. Carbohydrates protect the parenchymatous cells of the liver or of the
      kidneys from necrosis caused by any one of these substances. Chloroform is much
      more toxic to animals which have received a diet consisting in great part of fat
      than to those which have received meat. When fat is fed to the white rat fatty
      infiltration occurs in the centers of the hepatic lobules and in the loops of
      Henle of the kidney. The necrosis caused by chloroform has the same location. The
      solubility of chloroform in fat determines the increased susceptibility of
      animals which have received fat and stored it in the parenchymatous cells of the
      liver and kidney. Susceptibility to intoxication with phosphorus which causes
      fatty degeneration and necrosis of the liver is not increased by a diet of fat.
      Necrosis caused by phosphorus occurs in the periphery of the hepatic lobule and
      exhibits maximum intensity in animals which have received meat. Susceptibility to
      intoxication with potassium chromate which causes nephritis with necrosis of the
      convoluted tubules of the kidney is not greater after a diet of fat than after a
      diet of meat. Susceptibility to intoxication with uranium nitrate which causes
      nephritis with advanced necrosis of renal tubules is increased by a diet of fat.
      The loops of Henle, in which fat is abundant after a diet of fat, are the chief
      site of necrosis.

PMID- 19867850
TI  - A NEW AND RAPID METHOD FOR THE ISOLATION AND CULTIVATION OF TUBERCLE BACILLI
      DIRECTLY FROM THE SPUTUM AND FECES.
AB  - Sixty-nine positive cultures were obtained from sixty-nine specimens of sputum
      from practically all stages of tuberculosis. Six of these specimens were negative
      by direct microscopic examination, but the cultures gave positive findings. These
      six specimens have been positive for tubercle bacilli at some time. Nineteen
      positive cultures were isolated from thirty-two specimens of feces. All these
      thirty-two specimens, upon direct microscopical examination, gave positive
      findings, some showing only a few tubercle bacilli. Six specimens were not free
      from contaminating organisms, and the remaining seven were negative. The method
      presented in this paper has proved very simple and accurate for the isolation of
      tubercle bacilli from sputum. The partial success in isolating tubercle bacilli
      from feces may be due to the fact that many of the bacilli may be dead.

PMID- 19867851
TI  - THE FUNCTIONAL EFFECT OF EXPERIMENTAL INTRASPINAL INJECTIONS OF SERA WITH AND
      WITHOUT PRESERVATIVES.
AB  - The monkey (Macacus rhesus) usually tolerates readily the repeated intraspinal
      injection of large doses of 0.3 per cent. tricresol antimeningitis serum. The
      spontaneous respiration is generally not disturbed. Doses of 0.3 per cent.
      tricresol serum as large as 8 c.c. per kilo were injected intraspinally with
      subsequent recovery, even when the monkey had a partial pneumothorax. Dangerous
      alterations of the respiration and blood pressure in the monkey after 0.3 per
      cent. tricresol serum given by syringe are apparently largely due to increased
      intraspinal pressure, for the mere reduction of this pressure has sufficed to
      bring about a prompt and complete recovery. The medullary centers of the monkey
      (vagus, respiratory, and vasomotor) are highly resistant to the action of sera
      when injected intraspinally, strikingly more so than those of the dog.
      Occasionally the mere introduction of a hypodermic needle into the spinal dural
      sac of non-anesthetized, unoperated monkeys which have already received
      injections of 0.3 per cent. tricresol serum, may produce a severe collapse. A
      preceding partial asphyxia seems to be a necessary condition. Large quantities of
      sera are rapidly absorbed from the spinal dural sac of monkeys, and the clotting
      time of the blood is decreased. The spinal meninges of the monkey are resistant
      to infection; even primitive precautions during intraspinal injections apparently
      suffice to prevent infection. Dogs are much more sensitive to the intraspinal
      injection of 0.3 per cent. tricresol serum than monkeys; nevertheless they may
      tolerate as much as 6 c.c. per kilo provided that intratracheal insufflation is
      maintained for some time after each injection. The chief danger in dogs after
      intraspinal injections of 0.3 per cent. tricresol is a cessation of the
      respiration; for this reason artificial respiration is necessary. The blood
      pressure in the dog may be profoundly lowered by 0.3 per cent. tricresol serum,
      yet recovery is usually obtained if intratracheal insufflation is maintained. The
      effects of 0.3 per cent. tricresol serum upon the medullary centers is
      interpreted to be the result of either excitatory or inhibitory stimuli. No
      evidence was found that either the respiratory, vasomotor, or vagus center is
      paralyzed. The local application of 0.3 per cent. tricresol serum upon the
      exposed medulla of dogs does not produce the same effect upon the respiration and
      blood pressure as intraspinal injection of the same serum. A solution of 0.3 per
      cent. tricresol serum applied locally to the medulla of dogs occasionally
      produces a transient respiratory stop page, without markedly affecting the blood
      pressure even when intratracheal insufflation is stopped. Increased intraspinal
      pressure was found to be an important factor in the production of respiratory and
      blood pressure changes in the dog after intraspinal injection of 0.3 per cent.
      tricresol serum. Both in the monkey and in the dog 0.3 per cent. chloroform
      serum, 0.3 per cent. ether serum, or plain horse serum produced in general a
      smaller effect upon the medullary centers than 0.3 per cent. tricresol serum. The
      ideal preservative for therapeutic sera would seem to be one which could be
      removed before injection. Ether in this respect is better than chloroform. The
      opsonins in antimeningitis serum are about equally affected by 0.3 per cent.
      tricresol, 0.3 per cent. chloroform, or 0.3 per cent. ether when tested after one
      week, one month, and three months. When intraspinal injections are given in the
      human being it would seem advisable to be prepared to withdraw part of the
      injected fluid and to administer artificial respiration, if necessary. For a safe
      withdrawal of fluid the gravity method is the best; for artificial respiration
      Meltzer's apparatus for pharyngeal insufflation is recommended.

PMID- 19867852
TI  - THE FUNCTION OF THE SPLEEN IN THE EXPERIMENTAL INFECTION OF ALBINO MICE WITH
      BACILLUS TUBERCULOSIS : SECOND PAPER.
AB  - The resistance to an infection with the tubercle bacillus which can be given to
      mice by the removal of the spleen is lost when fresh spleen, either of mouse or
      sheep, is added to the diet. The logical conclusion that splenic function in its
      relation to the specific infection is restored by feeding spleen cannot, however,
      be drawn; because, in the first place, the character of the disease in the
      splenectomized spleen-fed animals differs somewhat from that in intact animals;
      and, secondly, because fresh spleen when fed to splenectomized animals apparently
      gives rise to an acute intoxication. This intoxication occurs quite regularly in
      mice. It is manifested in the infected animals and in those not inoculated. It
      has been seen in one of two splenectomized dogs experimented upon. Up to the
      present it can hardly be definitely characterized, but it seems to be best marked
      out by the specific anorexia associated with it.

PMID- 19867853
TI  - CONCERNING SURVIVAL AND VIRULENCE OF THE MICROORGANISM CULTIVATED FROM
      POLIOMYELITIC TISSUES.
AB  - The minute microorganism cultivated from poliomyelitic tissues survives and
      maintains its pathogenicity in cultures for more than one year. Upon inoculation
      into monkeys poliomyelitis may fail to appear upon the first injection and yet
      follow from the effects of successive injections of the culture. Inoculations of
      cultures into monkeys which fail to produce paralysis may fail also to induce
      resistance or immunity. In this respect the action of the cultures resembles that
      of the virus as contained in infected nervous tissues. The lesions occurring in
      the spinal cord, medulla, and intervertebral ganglia of the monkeys which respond
      to the several inoculations of the cultures are identical with those present in
      the nervous organs of the animals responding to injection of the ordinary virus.
      Glycerinated nervous tissues derived from the monkeys responding to several
      injections of the cultures transmit experimental poliomyelitis to monkeys upon
      intracerebral inoculation. The microorganism inoculated may be recovered in
      cultures from the monkeys which develop poliomyelitis; but cultivation from the
      brain tissue is attended with the usual difficulties surrounding the obtaining of
      the initial growth. The microorganism cultivated from poliomyelitic tissues is
      adapted with difficulty to saprophytic conditions of multiplication, but once
      adapted growth readily takes place upon suitable media. When, however, as a
      result of inoculation into monkeys, the parasitic propensities of the
      microorganism are restored, it again displays the marked fastidiousness to
      artificial conditions of multiplication present at the original isolation. The
      experiments reported in this paper afford additional strong evidence in support
      of the view already expressed, that this microorganism bears an etiological
      relationship to epidemic poliomyelitis in the human subject and to experimental
      poliomyelitis in the monkey.

PMID- 19867854
TI  - THE REACTIONS BETWEEN BACTERIA AND ANIMAL TISSUES UNDER CONDITIONS OF ARTIFICIAL
      CULTIVATION.
AB  - This report gives an outline of the results of observations on over 1,100 tissue
      cultures made during the fall, winter, and spring of 1913 to 1914. The work has
      been resumed in the fall of 1914 and will be continued along the same and allied
      lines, confirming the above results with other strains of the same organisms and
      with other bacteria and bacterial products. Tests should be made with tissue and
      plasma from other animals, and the known pathogenicity of the organism for the
      animal and tissue used should always be borne in mind. We hope to be able to grow
      on these cultures some of the more strictly parasitic bacteria not developing on
      ordinary media, as other strict parasites have been grown by other workers, viz.,
      poliomyelitis virus by Levaditi (4), vaccinia by Steinhardt, Israeli, and Lambert
      (5), and rabies by Moon (6). By comparative studies with various types of cells
      and various natural and artificial media, clearer ideas as to the exact part of
      cell plasma in antibody production, by elaborating on the methods of Carrel and
      Ingebrigtsen (7), Ludke (8), Przygode (9), and others, should be possible. After
      this work was begun a reference was found to the use of some pathogenic bacteria
      in tissue cultures by Pheiler and Lentz (10), but no publication of the results
      of these observations has been observed. The results here reported may be
      summarized as follows: Bactericidal Action of Chicken Plasma.-On Bacillus
      typhosus, very strong-never grows in plasma alone; on Bacillus prodigiosus, very
      strong-never grows in plasma alone; on Bacterium pseudodiphtheriticum, strong
      slight growth in cover-glass preparations; on Bacterium diphtheriticum,
      moderately strong; on Bacillus coli verus, slight; on Micrococcus aureus, very
      slight or none. A few pseudodiphtheria bacilli and more diphtheria bacilli
      survived in plasma stored in the cold for four days. The presence of growing
      tissue overcomes the bactericidal influence of plasma on diphtheria bacilli and
      in some instances on pseudodiphtheria bacilli. Bacterium diphtheriticum grows in
      plasma without tissue only if inoculations are very heavy; and very heavy
      inoculations of all organisms will probably overcome the bactericidal action of
      plasma, as it is undoubtedly a quantitative reaction. The bactericidal influence
      of plasma is overcome by exposure to incubator temperature for twenty-four to
      forty-eight hours. Bacterium diphtheriticum in light or moderate inoculations
      grows in tissue cultures only in clusters around the tissue fragments, and never
      in plasma away from tissue. The growth of this organism has a decided inhibitory
      influence on tissue activity and growth, especially marked with nervous tissue,
      but this action may be overcome by the addition of antitoxin to the plasma.
      Cultures inhibited by diphtheria growth have a tendency to resume growth later,
      probably due to antitoxin production. Bacterium pseudodiphtheriticum is
      distinctly less active in tissue cultures than is Bacterium diphtheriticum and
      never develops in plasma without tissue. The presence of diphtheria toxin in
      tissue cultures causes this organism to behave as does Bacterium diphtheriticum.
      Without toxin it has little or no direct influence on tissue growth except in
      massive doses. Bacillus prodigiosus fails to develop, as a rule, in tissue
      cultures except where inoculated from hypertonic media, and then it has no
      decided influence on tissue growth. Micrococcus aureus grows freely in these
      cultures with or without tissue, and inhibits tissue growth markedly, except as
      noted with splenic tissue. Bacillus coli verus always grows freely with or
      without tissue fragments and is uninfluenced by splenic tissue growth. In heavy
      inoculations it lessens tissue growth. Bacillus typhosus, except with extremely
      heavy inoculations, fails absolutely to grow in these cultures with or without
      plasma, unless the bactericidal action of the plasma has been destroyed by
      incubation. When this is the case it develops freely with especial affinity for
      the tissue cells either for support or nourishment. It appears to have no toxic
      action on the tissue cells. Note the sharp differentiation between typhoid and
      coli verus organisms. Diphtheria toxin has a quantitatively inhibiting action on
      all tissue growth and on heart tissue pulsations, the action being greatest on
      nervous tissue and least on heart tissue growth. Tissues affected by toxin tend
      to recovery if not killed. Antitoxin counteracts the action of toxin. Splenic
      tissue has little or no effect on the growth of Bacillus coli verus, but has a
      decided bactericidal action on Bacterium diphtheriticum and Micrococcus aureus,
      probably due to lymphatic cells and cell products, as seen by the area of cell
      migration coinciding with the bacteria-free area, by the similar action of
      splenic extract on cultures, and by the failure of such action in cultures of
      very early splenic tissue showing no lymphatic cells.

PMID- 19867855
TI  - VARIETIES OF PNEUMOCOCCUS AND THEIR RELATION TO LOBAR PNEUMONIA.
AB  - A study of pneumococci isolated from individuals suffering from lobar pneumonia
      has shown that the majority of these organisms fall into definite biological
      groups. These groups have been arbitrarily numbered from I to IV. The first three
      groups consist of organisms which within the group are closely related to each
      other by certain immunological reactions; i. e., protection and agglutination.
      Extensive study has failed to reveal crossing in either of these reactions
      between members of separate groups. The fourth group is formed of a series of
      independent varieties which cannot be definitely related to one another by the
      immune reactions employed. Up to the present time we have observed no tendency of
      these organisms to lose their specific characters, nor have we observed a change
      of one type into another. These groups vary in their pathogenicity for human
      beings, and in the order of their virulence are as follows: group III, group II,
      group I, group IV. The degree of protective power developed in the sera of
      animals immunized against members of the different groups varies inversely with
      the virulence and with the amount of capsular development. This, however, applies
      only to tests of passive immunity. The highly virulent groups give as good active
      immunity as those of lower virulence, if not better. In view of these constant
      differential characters of the pneumococcus, it was deemed advisable to study the
      pneumococci occurring in normal sputum. It has been commonly assumed that
      infection in pneumonia is autogenic, and occurs from the invasion of the lungs by
      a pneumococcus habitually carried in the mouth. If this is so, we should find the
      same types in the normal mouth as occur during the disease. Examination of a
      series of normal individuals showed this not to be the case. In no instance was
      an organism found which could be grouped with any of the fixed types of
      pneumococcus. All exhibited the same characters as those organisms obtained from
      lobar pneumonia which belong to group IV. Inasmuch as organisms belonging to this
      group are of low virulence, and are responsible in our experience for only 20 per
      cent. of the cases of pneumonia, it is at once manifest that the majority and
      more virulent cases of pneumonia are due to organisms which are not found in
      normal mouths. To gain further evidence of this difference, a study has been made
      of convalescents from pneumonia who had been infected by typical organisms.
      During the period of recovery these typical organisms are supplanted by the type
      which occurs in normal mouths. The period of disappearance of the typical
      varieties has varied. The shortest time in which disappearance has occurred has
      been twelve days, and the longest period in which typical organisms have been
      carried has been ninety days. In the latter instance the patient was lost sight
      of, so that he may well have carried the virulent form for a longer period of
      time. In general, when typical organisms persist for a long time, there is delay
      in the healing of the lung lesion. If recovery is prompt, as a rule the virulent
      types disappear rapidly. We have said that the virulent types do not occur in
      normal mouths. There are exceptions to this observation. In a number of instances
      organisms belonging to the typical groups have been isolated from the mouth
      sputum of healthy individuals. So far this has occurred only in individuals
      intimately in contact with cases of lobar pneumonia. Wherever typical organisms
      have been obtained under such circumstances, the type has always corresponded to
      that with which the case of pneumonia was infected. Such individuals, therefore,
      become infected with virulent types of pneumococcus by contact, and may be
      regarded as healthy carriers of disease-producing types. This study makes it
      probable that the majority of cases of pneumonia are dependent upon either direct
      or indirect contact with a previous case. Mere infection of the mouth by virulent
      types is by no means sufficient to cause the disease. In order to invade the
      lungs, these virulent types must find the circumstances favorable, or a suitable
      condition must arise during the period when they are harbored in the mouth.
      Comparative study of certain strains of pneumococci received from South Africa
      suggests that new groups of parasitic organisms develop only during the period of
      high racial susceptibility. A like condition of affairs is brought about when a
      group of hitherto unexposed individuals is brought into contact with an
      infectious microorganism. The development of racial immunity soon limits the
      number of new types which may arise. The suggestion is made that strictly
      parasitic races of microorganisms are pure lines and have established themselves
      as parasites during a period of high racial susceptibility.

PMID- 19867856
TI  - THE DISTRIBUTION OF THE IMMUNE BODIES OCCURRING IN ANTIPNEUMOCOCCUS SERUM.
AB  - The immune bodies of antipneumococcus serum are completely precipitated by 38 to
      42 per cent. saturation with ammonium sulphate. They are incompletely
      precipitated by (a) ammonium sulphate in less than 38 per cent. saturation, (b)
      saturation with sodium chloride, (c) dilution and saturation with carbon dioxide,
      (d) removal of crystalloids by dialysis. The immune bodies of antipneumococcus
      serum are, therefore, associated or combined with that fraction of the globulins
      precipitated by 38 to 42 per cent. saturation with ammonium sulphate. The immune
      body fraction does not correspond exactly with the ordinary euglobulin (one-third
      saturation with ammonium sulphate or complete saturation with sodium chloride) or
      with the insoluble globulins precipitated by carbon dioxide or dialysis. These
      fractions carry with them only a part of the immune bodies. Neither the albumin
      nor that fraction of the globulin not precipitated by 38 to 42 per cent.
      saturation of ammonium sulphate contain any of the demonstrable antibodies. The
      most promising method for the practical purification of the immune bodies
      occurring in antipneumococcus serum appears to be precipitation by 38 to 42 per
      cent. saturation with ammonium sulphate.

PMID- 19867857
TI  - THE TYPES OF PNEUMOCOCCI IN TUBERCULOUS SPUTUM.

PMID- 19867858
TI  - FURTHER INVESTIGATIONS ON THE MODE OF ACTION OF SUBSTANCES INHIBITING TUMOR
      GROWTH AND ON IMMUNIZATION AGAINST THESE SUBSTANCES.
AB  - Our later investigations confirm our previous results. 1. It is possible to
      increase markedly the effect of substances inhibiting tumor growth by using
      certain combinations of these substances which, when given alone, have some
      effect on tumor growth. 2. Immunity acquired against the effect of these
      substances depends partly upon an active immunization of the tumor cells
      themselves against the action of these substances, and this immunity is
      transmitted to the following generations of tumor cells. 3. The immunity against
      the substances inhibiting tumor growth is, as far as we have investigated the
      problem, specific. 4. Our later experiments provide a more secure basis for the
      additional and more general conclusions which we mentioned tentatively in our
      previous paper.

PMID- 19867859
TI  - A COMPARISON OF AUTOPLASTIC AND HOMEOPLASTIC TRANSPLANTATION OF THYROID TISSUE IN
      THE GUINEA PIG.
AB  - If we now consider briefly the principal results of our investigation, we can, in
      comparing the behavior of the thyroid after auto- and homeoplastic
      transplantation, in general recognize three stages. In the first stage,
      comprising the first 4 to 5 days after transplantation, there is no noticeable
      difference between the auto- and homeograft; both corresponding pieces behave in
      the main alike; large parts of both grafts become necrotic in the center; the
      necrosis begins shortly after the transplantation and concerns only a part of the
      periphery; here a narrow zone of thyroid tissue is left; it consists of one to
      two rows of partly well recognizable follicles. After 48 hours the first
      fibroblasts, polynuclear leucocytes, and lymphocytes appear in the tissue
      surrounding the grafts. After 72 hours these elements are present also in the
      center of the thyroid tissue. At the same date the first mitoses appear in the
      follicular epithelium; their number is, however, as yet small, but it increases
      markedly during the following days. After 4 days are found the first newly formed
      follicles, and from now on their number is increasing. Colloid is present only in
      small amounts in the old follicles. The central necrotic area still persists, but
      the masses of detritus are becoming smaller, while the number of fibroblasts and
      lymphocytes in the necrotic part is increasing; new blood vessels are also
      visible in the necrotic center. The second stage, the stage of transition,
      extends over the next seven days. The earliest, at first slight, differences
      between the auto- and homeograft appear after 5 days; the difference is usually
      very definite after 12 days. During this time there is an increase in the number
      of follicles in the autograft and correspondingly a decrease in the size of the
      necrotic central area, which is caused by a gradually progressing removal of the
      necrotic material in the center of the piece. The follicles are lined with a high
      cylindrical epithelium, which contains numerous mitoses. The number of mitoses
      increases markedly after the 4th day and reaches a maximum between the 7th and
      9th days. Newly produced colloid is always present in the autograft after the 8th
      day; in the newly formed follicles the colloid contains numerous vacuoles and is
      almost never retracted, in contradistinction to the solid retracted colloid in
      the old follicles, which probably was present in the follicles at the time of
      transplantation. At the end of this period the central part is almost entirely
      freed from the necrotic masses and is filled with loosely arranged connective
      tissue cells, between which isolated lymphocytes and polynuclear leucocytes can
      be found. It contains also numerous blood vessels and brown blood pigment cells.
      After 5 days, with the beginning of the second stage, the first as yet rather
      insignificant differences become noticeable in the homeotransplants. They are as
      follows: (1) The number of lymphocytes is much larger in the homeo- than in the
      autograft. (2) The fibroblasts are increased in the central area and these
      fibroblasts form here very soon firm connective tissue bundles; they surround
      also the individual follicles or small groups of follicles and form fibrous
      bands, which are at this stage still very small. During the following days the
      number of lymphocytes increases and the fibrous connective tissue becomes more
      prominent, so that 7, 9, 10, and 11 days after transplantation numerous follicles
      are not only destroyed by the surrounding and invading lymphocytes, but in
      addition a part of the follicles is encircled and compressed by wide connective
      tissue bands. This compression is especially distinct in the central parts of the
      homeografts. At this stage the absence of a well developed vascular system is
      already noticeable in the central parts of the homeografts. It is especially
      noteworthy that the follicles of the homeograft which escaped destruction by the
      lymphocytes and connective tissue are as well preserved as in the autograft.
      Colloid is usually present in smaller amounts than in the autografts, even in the
      well preserved follicles of the homeografts. It must, however, be stated that
      some variations occur in this stage in the degree of destruction of the
      homeotransplanted pieces. Side by side with pieces in which a marked destruction
      has taken place, there are other pieces which suffered as yet relatively little.
      But some of the above mentioned differences between the auto- and
      homeotransplants are always present to a smaller or larger extent. There are also
      certain variations in the relative strength, with which lymphocytes and
      connective tissue injure the follicles; in some homeotransplants the attacks on
      the part of the lymphocytes prevail, while in others those on the part of the
      connective tissue are more prominent. The homeotransplants, which are relatively
      little injured at this stage are spared only to be subject to a stronger attack
      on the part of the lymphocytes and connective tissue during the following stage.
      The third stage begins approximately with the 12th day. From now on the
      difference between auto- and homeograft is sharply defined. In the autografts the
      regeneration of the thyroid tissue is steadily progressing and is nearly complete
      after 21 days. After this date the autograft represents throughout the picture of
      the normal thyroid gland; well developed follicles filled with colloid are
      surrounded by a very scant connective tissue. Mitoses, which begin already to
      decrease after the 9th day, are still present at the end of 17 days, but absent
      after this date. The small amount of loosely built, usually centrally located
      connective tissue, has no tendency to undergo a fibrous or hyaline change and
      does nowhere exert a compression on the follicles. It contains always a large
      number of blood vessels and only a few lymphocytes. In the homeograft the
      secondary destruction of the follicles is progressing with great intensity after
      the 12th day. In contradistinction to a primary degeneration of the follicles,
      due to the action of substances circulating in the body fluids, which might have
      been expected to take place, but which in reality does not occur, and which would
      be followed only secondarily by a connective tissue proliferation and lymphocytic
      invasion, we may speak of the destruction by means of lymphocytes and connective
      tissue, which actually does take place, as a secondary destruction of the
      follicles. This secondary mode of destruction of the follicles through
      lymphocytes and connective tissue is found exclusively in the homeotransplant.
      Following this destruction the larger part of the homeografts is occupied by a
      fibrous, hyaline connective tissue, in which remnants of destroyed follicles in
      the form of clefts filled with lymphocytes are seen. In several cases the
      destruction of follicles through lymphocytes, which accumulate in large numbers
      around the follicles and destroy them very actively, prevails; in other cases the
      compression of the follicles through fibrous, hyaline connective tissue
      predominates; in other cases both factors may be about equally active. The few
      peripheral follicles which escaped destruction are small, probably as a result of
      compression through the connective tissue; but they may still show normal
      epithelium and nuclei and may occasionally contain traces of colloid. Newly
      formed colloid is not present in the homeotransplants at the third stage. It
      should also be mentioned that the blood supply of the homeografts, especially
      after the 12th day, is very much restricted and that the blood vessels are mainly
      located in the connective tissue surrounding the graft, and not in the central
      connective tissue, which exists here in a much larger quantity and is much denser
      than in the autograft. At this stage also we find considerable variations in the
      extent of the injuries, in the individual follicles. But no piece escapes the
      attack entirely, and those which remain relatively well preserved for a certain
      period will be attacked at a later date by the connective tissue, as well as by
      the lymphocytes of the host. To summarize briefly, the principal result: For a
      short period of time after operation no difference is seen in the behavior of the
      thyroid after auto- and homeotransplantation. Very soon, however, a destruction
      of follicles begins to take place in the homeografts. This destruction is not
      caused by a direct primary disintegration or solution of follicles, but depends
      on the destructive activity of (1) the lymphocytes, and (2) of the connective
      tissue of the host tissue. The former invade the follicles and destroy them
      directly; the latter grows into the homeografts in larger quantity than into the
      autografts. In the former it soon becomes fibrous and hyaline; in the latter it
      remains cellular. The fibrous connective tissue surrounds and compresses and thus
      destroys the follicles. In some homeografts destruction by means of lymphocytes,
      in others by connective tissue, preponderates. The rapidity with which the
      destruction takes place in different homeotransplants also varies. A much better
      blood vessel supply develops in the autograft than in the homeograft.

PMID- 19867860
TI  - NOTES ON THE SUBCUTANEOUS ABSORPTION AND THE QUANTITATIVE ESTIMATION OF
      CHOLESTEROL.
AB  - Cholesterol, in 0.1 gram amounts, melted in a compact mass and inserted into the
      subcutaneous tissues of the back of the guinea pig, is slowly removed, as
      determined by chemical analyses. The rate of removal is probably greatly
      dependent upon the physical state of the cholesterol. The quantitative estimation
      of cholesterol by the method previously described can not be shortened and
      simplified by the direct saponification of the tissues by means of 5 per cent.
      sodium alcoholate or a strong (50 per cent.) solution of sodium hydroxide,
      instead of saponifying the alcohol-ether extract.

PMID- 19867861
TI  - THE RESISTANCE OF PUPS TO LATE CHLOROFORM POISONING IN ITS RELATION TO LIVER
      GLYCOGEN.
AB  - The relative difficulty with which the characteristic central lobular liver
      necrosis can be produced in young pups after chloroform administration is in some
      way referable to the high glycogen contents of their livers. Evidence for this
      conclusion lies in the following facts: 1. Pups can readily be made to show the
      central liver necrosis which is found in chloroform poisoning in adults, if,
      prior to the administration of chloroform, they have been starved or starved and
      made diabetic by phlorhizin. 2. A single quantitative experiment showed that the
      liver of a normal, well nourished pup, twenty-four hours old, contained as much
      as 9.07 per cent. of glycogen. 3. The feeding of carbohydrates to adult animals
      lessens their susceptibility to the production of liver necrosis by chloroform.

PMID- 19867862
TI  - THE RELATION BETWEEN THE STRUCTURE OF THE EPIDERMIS OF THE RAT AND THE GUINEA
      PIG, AND THE PROLIFERATIVE POWER OF NORMAL AND REGENERATING EPITHELIAL CELLS OF
      THE SAME SPECIES.
AB  - 1. A comparative study of the resting and regenerating epidermis of the rat,
      pigeon, and guinea pig shows the connection between the structure of the skin and
      the proliferating power of the epithelial cells. We may at present distinguish
      two types of epidermal cells: (a) cells with less proliferative energy (pigeon
      and rat), and (b) cells with a greater proliferative power (guinea pig); the
      former provides the element from which the type of a thin epidermis is built up,
      while from the latter the type of a thick epidermis develops. 2. The cell type
      with greater proliferative power in the normal skin shows also greater
      proliferative power during regeneration, and the regenerative stimulus causes
      approximately the same relative increase in the number and size of cells and
      nuclei in both kinds of skin during regeneration, provided that we base our
      determination of the number of mitoses on the same unit number of cells in both
      skins rather than on the same unit area. The absolute increase in the number of
      cells during regeneration is greatest in the type with the greatest proliferative
      power in the normal cell (guinea pig). 3. The number of mitoses and the size of
      cells and nuclei follow a similar curve in the different species during
      regeneration. They reach a maximum approximately on the 7th day; remain
      stationary or show some decline from the 7th day on until the time of the closure
      of the wound; following the closure a further fall takes place; but the figures
      remain higher than in the normal epidermis for a considerable period afterwards.
      There seems, therefore, to exist under the conditions of our experimentation a
      period of approximately 7 days, at the end of which the regenerative stimulus
      reaches its maximum effect. The closure of the wound represents probably an
      additional factor determining the curve of cell proliferation. Failure of the
      wound to close at an early date seems to make the decline in the number of
      mitoses sharp after the maximum has been reached. 4. The curve representing the
      thickness of living regenerating epithelium declines much more slowly than the
      curve representing cell size and number of mitoses. This indicates probably that
      even after closure of the wound some push of epithelial cell towards the center
      of the former wound continues to take place. 5. From the second day the
      additional growth of the epidermal tongue decreases in each successive period, if
      we use the length of the tongue at the beginning of each period as the unit of
      measurement. 6. Retraction and contraction of the wound are factors additional to
      epithelial movements and epithelial proliferation determining the closure of the
      wound.

PMID- 19867863
TI  - LIVER FUNCTION AS INFLUENCED BY ANESTHETICS AND NARCOTICS.
AB  - It has been established that specific liver poisons (chloroform, phosphorus)
      which cause histological changes in the liver cells, decrease the liver excretion
      of phenoltetrachlorphthalein. Also vascular disturbances (Eck fistula, passive
      congestion) with or without histological evidence may cause a fall in the output
      of phthalein through the liver. Sufficient evidence has been brought forward to
      show that the phenoltetrachlorphthalein excretion is a valuable index concerning
      the functional capacity of the liver. Ether anesthesia for a period of two hours
      usually causes a depression in the phthalein curve during the twenty-four hours
      following the anesthesia. Paraldehyde in doses sufficient to give anesthesia and
      stupor for a few hours will give adefinite fall in phthalein excretion. Chloral
      and urethane usually cause a decrease in phthalein output when given in
      considerable amounts. Alcohol causes a drop in the phthalein curve when given in
      large doses sufficient to cause stupor for a few hours. The drop in
      phenoltetrachlorphthalein excretion is demonstrated in the twenty-four hours
      following administration of the drug. A drop in the phthalein curve to two-thirds
      or one-half of normal indicates a definite liver injury and temporary impairment
      of function.

PMID- 19867864
TI  - NOTES ON THE CULTIVATION OF TREPONEMA PALLIDUM.
AB  - We consider themost importantcontribution reported in this paper the fact that
      Treponema pallidum can be cultivated in fluid media, without the addition of
      agar, together with tissues sterilized by heat. This forms an excellent method of
      obtaining mass cultures for luetin preparation and immunological experimentation.
      We may add that while the tissue varieties employed have all stongly favored the
      growth of the treponemata, we have noticed especially active and motile cultures
      when lung and suprarenal tissues were employed.

PMID- 19867865
TI  - THE MECHANISM OF THE ABDERHALDEN REACTION : STUDIES ON IMMUNITY. I.
AB  - 1. The Abderhalden reaction is specific. 2. The properties of serum on which it
      depends develop in experimental animals simultaneously with antibodies during the
      process of immunization. 3. It is impossible to observe by direct methods the
      presence of digesting ferments in the blood of immune animals. 4. The Abderhalden
      test may be resolved into two phases. A dialyzable substance appears in the
      second phase and is the result of the autodigestion of serum. 5. The
      autodigestion of serum in the Abderhalden test is due to the removal of
      antitrypsin from the serum by the sensitized substratum.

PMID- 19867866
TI  - SERUM PROTEASES AND THE MECHANISM OF THE ABDERHALDEN REACTION : STUDIES ON
      FERMENT ACTION. XX.
AB  - 1. Normal serum protease is not specific; it is active in both dilute acid as
      well as alkaline media. It is destroyed by heating to 70 degrees C. for thirty
      minutes. It is markedly impaired when heated at 56 degrees C. for thirty minutes.
      It is inhibited by the unsaturated soaps and lipoids. 2. Guinea pig and rabbit
      serum contain relatively much protease; the leucocytes are without proteolytic
      ferments. 3. Normal human and dog serum contain little or no protease; the
      leucocytes are strongly proteolytic. 4. Serum complement and protease are not
      identical. 5. During various pathological conditions the non-specific protease is
      increased in both human and dog serum. 6. An increase in antiferment is in many
      instances coincident. 7. During the Abderhalden reaction the placental tissue
      becomes more resistant to enzyme action, because of the adsorption of the
      antiferment from the serum. 8. The dialyzed serum loses antiferment because of
      adsorption by the placental tissue or other adsorbing substances, including
      probably the dialyzing membrane. 9. The digestive substrate is the serum protein
      made available for protease action by the adsorption of the antiferment. 10. The
      proteases in pathological conditions investigated by us (pregnancy, tuberculosis,
      and pneumonia) are non-specific.

PMID- 19867867
TI  - THE INFLUENCE THAT SERUM EXERTS UPON TRYPANOSOMES, WITH SPECIAL REFERENCE TO ITS
      USE FOR EXPERIMENTS IN VITRO WITH ATOXYL AND PARAMINO-PHENYLARSENOXYD.
AB  - 1. Serum of various animals preserves the motility of nagana trypanosomes better
      and longer than salt solution. 2. To act best in this way the serum should not be
      diluted more than 2 to 4 times. Undiluted serum is perhaps best. 3. Serum
      filtered through a Berkefeld filter, bottled aseptically, and kept in the ice box
      preserves this activating property apparently undiminished for many months. 4.
      Serum preserves the motility of trypanosomes better than "Sals physiologicum" of
      Merck, and better than the Ringer solutions of Meltzer and Carrel. 5. Serum
      preserves the normal morphology of trypanosomes better than the Ringer solutions
      tested. 6. The infectiousness of trypanosomes suspended in cattle serum was
      preserved at room temperature for at least 8 days. 7. The vitality of the
      trypanosomes in serum was seemingly better preserved at room temperature than at
      ice box temperature. 8. Serum incubated with atoxyl does not transform it into a
      toxic substance. 9. Serum does not bind paraminophenylarsenoxyd, for trypanosomes
      suspended in serum are often immobilized more quickly by paraminophenylarsenoxyd
      than trypanosomes suspended in salt solution. 10. Serum is suitable for
      suspending trypanosomes for certain experiments in vitro, and with proper
      precautions may be employed for transporting virus from laboratory to laboratory.

PMID- 19867868
TI  - DIFFERENT AMOUNTS OF TRANSFORMED ATOXYL PRODUCED BY INCUBATING ONE PER CENT. AND
      TEN PER CENT. ATOXYL IN BLOOD.
AB  - 1. 10 per cent. atoxyl in blood incubated at 37 degrees C. for 1 hour gives rise
      to a solution that is much more than ten times as toxic as a 1 per cent. solution
      of atoxyl similarly incubated. 2. When the comparison is made after incubation
      for 3 hours instead of for 1 hour, the toxicity of the 10 per cent. solution is
      but slightly greater than ten times that of the 1 per cent., provided the red
      blood corpuscles are not removed from the dilutions. 3. If the corpuscles are
      removed from both the 10 per cent. and the 1 per cent. atoxyl solutions
      immediately after incubation at 37 degrees for 1 to 3 hours, the dilutions of the
      10 per cent. atoxyl are much more than ten times as toxic as the corresponding
      dilutions of the 1 per cent. atoxyl. 4. After incubation with atoxyl at 37
      degrees for 1 to 3 hours, red blood corpuscles left at room temperature in
      dilutions made from the 10 per cent. and 1 per cent. solutions in blood increase
      markedly the toxicity of the dilutions made from the 1 per cent. atoxyl, but
      increase very slightly the toxicity of the dilutions made from the 10 per cent.
      atoxyl. 5. If one desires to produce a large amount of transformed atoxyl by
      incubating atoxyl in blood at 37 degrees for 1 to 3 hours, strong solutions of
      atoxyl should be chosen in preference to weaker solutions.

PMID- 19867869
TI  - THE EFFECT OF HEAT ON THE TRANSFORMING AND BINDING POWER OF BLOOD.
AB  - 1. The transforming power of red blood cells for atoxyl is apparently
      uninfluenced by a preliminary heating of the blood for 30 minutes at 50 degrees
      C., but a temperature of 55 degrees C. acting for 30 minutes destroys this
      property of blood almost completely. 2. When the heating was for 60 minutes, 54
      degrees C. and higher temperatures apparently destroyed all the transforming
      power. 3. After heating for 10 minutes, 70 degrees C. destroyed almost all the
      transforming power, and 100 degrees C. seemingly destroyed all. 4. Under the
      influence of certain temperatures blood seemingly binds transformed atoxyl, and
      under the influence of other temperatures frees it again. A temperature of 70
      degrees C. for 10 minutes applied to blood subsequent to its incubation with
      atoxyl causes nearly all the toxicity of the solution to disappear. On the other
      hand, a temperature of 100 degrees C. for 10 minutes applied to blood subsequent
      to incubation with atoxyl leaves the solution almost as toxic as if the blood had
      not been heated at all after the incubation. 5. Some of the transformed atoxyl
      bound by blood when it is heated to 70 degrees C. for 10 minutes is freed if the
      heating at 70 degrees C. is prolonged to 30 minutes. See PDF for Structure 6.
      Blood which has bound transformed atoxyl gives up most, but not all, of this
      toxic substance when heated to 100 degrees for 10 minutes. All, or nearly all, is
      freed when the heating at 100 degrees C. is continued for 30 minutes. 7. Under
      the influence of 70 degrees C. for io minutes transformed atoxyl may be made to
      enter blood corpuscles, for the fluid above these corpuscles is rendered non
      toxic and does not become toxic again when heated to 100 degrees for 20 minutes,
      provided it contains no laked blood. The blood corpuscles, on the other hand,
      when heated to 100 degrees for 20 minutes in contact with fresh salt solution,
      make this solution quite toxic. 8. Laked blood in contact with transformed atoxyl
      behaves like unlaked blood when heated to 70 degrees C. and to 100 degrees C. for
      10 to 30 minutes. 9. The toxic substance can be concentrated by heating the blood
      corpuscles in contact with transformed atoxyl to 70 degrees C. for 10 minutes,
      centrifugalizing, removing a large part of the supernatant fluid, and then
      heating to 100 degrees C. for 30 minutes. 10. The power of blood to take up and
      bind transformed atoxyl is destroyed apparently completely by heating blood to
      100 degrees C. for 10 minutes. 11. The toxic substance into which atoxyl is
      transformed (transformed atoxyl) is thermostabile, but the transforming agent in
      blood is thermolabile.

PMID- 19867870
TI  - THE INFLUENCE OF THE ANTERIOR LOBE OF THE PITUITARY BODY UPON THE GROWTH OF
      CARCINOMATA.
AB  - 1. The administration of emulsions of the anterior lobe of the ox pituitary
      increases very markedly the rate of growth of the primary tumor in rats
      inoculated with carcinoma. The growth of small tumors is accelerated relatively
      more than that of large tumors. 2. This acceleration is only evidenced, however,
      at a certain stage in the growth of the tumor, subsequent to the twentieth day
      succeeding inoculation. The administrations do not enhance the tendency of the
      tumors to metastasize. 3. Liver emulsion does not cause an acceleration of the
      growth of carcinomata in rats.

PMID- 19867871
TI  - A COMPARISON OF ADULT AND INFANT TYPES OF GONOCOCCI.
AB  - 1. Two principal types of gonococci may be recognized by suitable immunological
      tests; e. g., agglutination and complement fixation. These two types correspond
      to the adult and infant types of infection with the gonococcus, seen clinically.
      2. On the basis of the immunological reactions of agglutination and complement
      fixation the strains of gonococci isolated from three cases of ophthalmia are
      classed with the adult type. 3. A polyvalent antigen for the serological
      diagnosis of a gonococcus infection should represent strains of the infant type
      of organism in order that both types of infection, infant as well as adult, may
      be recognized.

PMID- 19867872
TI  - STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : VII. THE PRODUCTION OF LOBAR
      PNEUMONIA.
AB  - 1. The production of lobar pneumonia in rabbits is dependent upon the
      introduction of organisms into the alveoli themselves. 2. In order to accomplish
      this the catheter through which they are injected must be inserted as deeply into
      a bronchus as possible and the culture fluid injected with considerable force. 3.
      Large numbers of organisms injected into the trachea just beyond the larynx set
      up no great changes in the lungs, even though the injection be forcible. This
      fact suggests the presence of a protective mechanism in the upper air passages,
      which, under normal conditions, prevents the penetration of organisms into the
      lungs. 4. If animals be subjected to cold, alcohol, and the inhalation of
      irritating gases, the so called secondary factors in the etiology of lobar
      pneumonia in man, then the injection of pneumococci into the trachea causes
      inflammatory changes of the upper respiratory tract and occasionally pneumonia.
      5. The vagi prevent foreign material in the pharynx and upper respiratory tract
      from reaching the lungs. Section of one vagus may be followed by pneumonia, while
      section of both invariably leads to this result. 6. It is possible that the
      secondary factors mentioned above owe their action to their influence upon the
      vagus control of the upper respiratory tract.

PMID- 19867873
TI  - STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : VIII. INTRA VITAM STAINING IN
      EXPERIMENTAL PNEUMONIA, AND THE CIRCULATION IN THE PNEUMONIC LUNG.
AB  - 1. Dead leucocytes are constantly found in the pneumonic exudate. They rapidly
      undergo disintegration. Up to the seventh day they do not form the majority of
      the cells of the exudate. 2. Polymorphonuclear leucocytes with vitally stained
      granules are present in the exudate, vessels, and interstitial tissue of the lung
      in experimental pneumonia, but they are not demonstrable in the general
      circulation in the same animals. 3. There is a marked impairment of the
      circulation in the pneumonic lung. 4. The increase in the intra-alveolar pressure
      exerted by the exudate has no influence upon the circulation. 5. The impaired
      circulation results from the wide distribution of capillary fibrin thrombi. In
      man these are, as a rule, distributed with relative uniformity. In the rabbit
      this is not usually the case. The thrombi are much more abundant in some areas
      and may lead to localized necrosis. 6. The impairment of the circulation is of
      importance in bringing about resolution. Only enough blood is allowed to seep
      through the vessels to nourish the alveolar walls. Consequently very little serum
      escapes into the alveoli and the autolysis of the exudate by the leucocytes is
      unhindered. 7. The impairment of the circulation in the pneumonic lung seriously
      interferes with the action of intravenous therapy upon the local lesion. 8. The
      exudate in the pneumonic lung can be readily impregnated with a dye injected
      intrabronchially. This suggests a method of administration of therapeutic agents
      in pneumonia.

PMID- 19867874
TI  - STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : IX. THE PART OF THE LEUCOCYTE IN
      THE IMMUNITY REACTION.
AB  - Following the intravenous injection of an overwhelming dose of pneumococci in
      normal animals there is a rapidly increasing bacteriemia which reaches its
      maximum with the death of the animal. Immunized animals, whether the immunity is
      active or passive, whether the animals have their leucocytes, or whether these
      have been destroyed by benzol, react differently. They have incommon the ability
      to cause the organisms to decrease rapidly in number, and, as far as could be
      determined by the methods used, to disappear absolutely in a very short time from
      the circulation. This may be called the immediate reaction. In actively and
      passively immunized normal rabbits the disappearance of the organisms from the
      blood is followed by their destruction in the body and the ultimate recovery of
      the animal. This same result occurs also in actively immunized rabbits deprived
      of their polymorphonuclear leucocytes by benzol. On the contrary, in passively
      immunized rabbits, deprived of their leucocytes in the same way, the immediate
      disappearance of the organisms from the circulation is followed, after a lapse of
      from six to twenty-four hours, by a recurrent, gradually increasing bacteriemia
      and the death of the animal. It is evident that the immediate reaction is no
      index of the ultimate result. This finding, that the result of the intravenous
      injection of an overwhelming dose of pneumococci in immunized animals may be
      divided into two stages, immediate and ultimate, has been utilized in the
      interpretation of the experiments that have been reported above. 1. Normal
      Rabbits.-In the normal rabbit the injection of a lethal dose of pneumococci is
      followed by the same immediate and ultimate response. The animal develops a
      rapidly progressing bacteriemia and dies. 2. Passively Immunised Normal Rabbits.
      A diametrically opposed finding is obtained when the animals are passively
      immunized. Then following the intravenous injection of pneumococci the organisms
      rapidly disappear from the circulating blood and the animal recovers. The only
      apparent difference between these two groups of experiments is the introduction
      of a relatively small quantity of immune serum. Tentatively, therefore, it may be
      concluded that the immune serum is responsible both for the immediate and
      ultimate reaction in this case. 3. Passively Immunized Aplastic Rabbits.-A normal
      rabbit that has been previously benzolized, and in this way deprived of its
      myeloid elements, can not be successfully immunized. Here the immune serum
      injected even in excessive quantities is followed by the immediate reaction, but
      the ultimate result is entirely different, -the animal dies. It may be concluded,
      therefore, that the serum is the potent factor in bringing about the immediate
      disappearance of the organisms from the circulation. Furthermore, it is evident
      that the white blood cells of the myeloid tissue are necessary in order that
      passively immunized animals may recover following the introduction of a lethal
      dose of pneumococci. So far it seems that two elements are essential in the
      immunity process; i. e., immune bodies and white blood cells. Corroborative
      evidence of the importance of the white blood cell in this reaction is offered by
      the hyperleucocytosis which follows the injection of antigen in actively
      immunized animals (Gay). This hyperleucocytosis occurs in actively immunized
      rabbits injected with pneumococci, after the organisms have disappeared from the
      circulation. It occurs at about the same time that the septicemia recurs in
      passively immunized aplastic rabbits. 4. Actively Immunized Aplastic Rabbits.-The
      experiments with actively immunized aplastic rabbits complicate the conception of
      the part of the white blood cells in the immunity process. When actively
      immunized, benzolized animals are injected with a lethal dose of pneumococci, the
      immediate reaction occurs just as in the passively immunized aplastic animal.
      Available antibodies are present and cause the disappearance of the organisms
      from the circulation. The ultimate reaction differs from that in the passively
      immunized aplastic animal. The latter develops a recurrent bacteriemia and dies.
      The actively immunized aplastic animal recovers. It would seem that the white
      blood cell is no longer necessary in an animal that has been actively immunized,
      but that it must be present for the passive protection of the animal. The
      ultimate reaction in immunized rabbits seems to be dependent upon some action of
      the white blood cells. In the passively immunized animal this may occur at the
      time of, or following, the immediate reaction; and if it can not occur, owing to
      the absence of the white blood cells, the animal subsequently dies. In the
      actively immunized aplastic rabbit this action has apparently occurred at a
      previous time and is sufficiently developed to protect the animal even though the
      leucocytes have been destroyed. It may be assumed that the function of the white
      blood cell is exercised not directly, but perhaps indirectly, by some influence
      exerted on other body cells. This interrelation or interaction between the white
      blood cells and other cells in the body constitutes a third factor essential to
      the ultimate protection of the animal. Additional evidence of this action of the
      white blood cell is furnished by further experiments with actively immunized
      aplastic rabbits. Several immunized rabbits were benzolized and then injected
      with a lethal dose of pneumococci. The results were the same as those indicated
      above. The organisms disappeared rapidly from the circulation and the animals
      recovered. An interval of five days was allowed to elapse and the animals were
      injected again with the same amount of pneumococci. This time the reaction was
      different. The organisms disappeared rapidly from the circulation, but there was
      a recurrent bacteriemia and the animals died. In these animals the favorable
      ultimate result after the first inoculation of a lethal dose of pneumococci
      probably depended upon the presence of the immune bodies and the third factor
      mentioned above. After the subsequent inoculation of pneumococci the immediate
      reaction was followed by the recurrence of the bacteriemia and the death of the
      animals. It may, therefore, be inferred that the third factor present at the time
      of the first injection had been destroyed, and, owing to the absence of white
      blood cells at the time of the subsequent inoculation, it was not formed again.
      It may be concluded that there are at least three elements necessary in the
      immunization process: (l) immune bodies, (2) white blood cells, and (3)a third
      factor which is dependent for its existence upon the presence of white blood
      cells at the time of inoculation of the pneumococci. Furthermore, this third
      factor may be removed if the animal is inoculated at a time when it is aplastic.

PMID- 19867875
TI  - THE INFLUENCE OF EPINEPHRIN UPON THE CORONARY CIRCULATION OF THE MONKEY.
AB  - Decrease in coronary flow was the constant response of freshly isolated monkey
      hearts to epinephrin. These hearts were perfused with autogenous hirudinized
      blood diluted with Locke solution. The results were constant at high or low
      perfusion pressures, in beating or resting hearts, and with all adequate doses.
      Increased coronary flow was obtained constantly in rabbit hearts under identical
      conditions. In the light of previous work upon isolated human coronary arteries,
      the general conclusion is drawn that, while actively dilating the coronary
      vessels in the dog, cat, rabbit, ox, sheep, and pig, epinephrin constricts the
      coronary vessels in man and the monkey. The coronary arteries of the last two
      species are presumably supplied with constrictor nerves of true sympathetic
      (thoracicolumbar) origin.

PMID- 19867876
TI  - A TEST FOR ANTITHROMBIN IN THE BLOOD.
AB  - A test is described for the estimation of antithrombin in the blood. The chief
      advantage of the test is that it is simple, and does not require the preparation
      of fibrinogen and of thrombin, which are difficult to prepare and to maintain in
      a pure state. The principle consists in titrating the antithrombin against normal
      human plasma; in this way we obtain an estimation of its power to delay
      coagulation. As the result of examinations carried out by this method, it would
      seem that there is a wide factor of safety as regards the amount of antithrombin
      in the human blood, and that this inhibiting substance may be increased to a
      considerable degree without markedly delaying or endangering clotting.

PMID- 19867877
TI  - CONCERNING CHANGES IN THE BIOLOGICAL PROPERTIES OF TRYPANOSOMA LEWISI PRODUCED BY
      EXPERIMENTAL MEANS, WITH ESPECIAL REFERENCE TO VIRULENCE.
AB  - 1. Different strains of Trypanosoma lewisi represent different states of
      biological balance, especially between the powers of propagation and resistance
      to destruction. 2. The biological status of a given strain of Trypanosoma lewisi
      is subject to cyclic variations as the result of immunological reactions in the
      blood of the host. 3. The factors limiting reproduction and causing destruction
      of Trypanosoma lewisi in the blood are appreciably independent of each other. It
      is possible, therefore, to influence these processes separately and even in
      opposite directions. 4. The virulence of Trypanosoma lewisi, manifested in its
      highest form, is dependent upon some degree of reproductive fastness, strong
      antigenic action, and susceptibility to destruction, varying degrees in the
      development of these properties producing corresponding variations in the degree
      of virulence. 5. By a properly regulated system of passage the properties of
      Trypanosoma lewisi that determine its infection cycle and its virulence may be
      eventually so altered as to change completely both the nature and course of the
      infection. Such a system of passage must be adapted to the particular strain of
      Trypanosoma lewisi used. 6. Immunological reactions exercise a dominant influence
      in determining the ultimate biological variations of Trypanosoma lewisi.

PMID- 19867878
TI  - THE INFLUENCE OF MILK FEEDING ON MORTALITY AND GROWTH, AND ON THE CHARACTER OF
      THE INTESTINAL FLORA.
AB  - Throughout the investigations upon which a large part of this paper is based the
      favorable influence of milk feeding on mortality and growth was most apparent.
      Mortality from all causes was frequently reduced to at least one-half of what
      obtained among the chicks that received no milk, while the milk-fed chicks in
      some experiments gained twice as much in weight as those that were without this
      article of diet. Although the influence of milk feeding was less pronounced on
      the mortality of chicks that were artificially infected with Bacterium pullorum,
      quite an appreciable difference in mortality was always noted if the milk was fed
      at least one or two days before the first administration of the bouillon cultures
      of the organism in question. Practically the same results were obtained, whether
      sweet or sour milk was fed, and no differences could be observed in the relative
      value of ordinary sour milk and of the so called bulgaricus product. Hence, the
      unique properties of this food exist in the milk as such, rather than in any milk
      acids or milk bacteria that may be present. Milk and lactose diet exert a very
      important influence on the character of the intestinal bacteria, especially in
      white rats and in the common domestic fowl. Within a few days after the ingestion
      of milk or lactose a transformation of the flora takes place in which the usual
      mixed bacterial flora give way to ones that are more simplified, and in which
      Bacillus acidophilus and Bacillus bifidus are, as a rule, prominent. It is to be
      assumed that milk has this influence in virtue of the large amount of lactose
      which it contains. Other carbohydrates, besides milk sugar, failed to bring about
      such a transformation. The ingestion of foreign bacteria, even in large numbers,
      does not of itself bring about an elimination or displacement of the common
      intestinal microorganisms. Vastly more important is the influence of diet,
      especially milk and lactose. The feeding of Bulgara tablets or other preparations
      which contain as the supposedly active agent the bacillus of Metchnikoff and
      Maze, without due regard to the use of milk, can, therefore, be of little, if
      indeed of any, value. The beneficial effects which it is claimed have been
      derived from the use of yoghurt, and other oriental sour milk products have in
      all probability been due to the milk as such, rather than to the bacteria which
      they contained. This view is strongly supported by the extensive milk feeding
      experiments on chicks which are recorded in this paper, and also by the results
      which show the influence of milk and of lactose feeding on the intestinal flora
      of white rats and of the common domestic fowl.

PMID- 19867879
TI  - CONCENTRATION OF THE PROTECTIVE BODIES IN ANTIPNEUMOCOCCUS SERUM BY MEANS OF
      SPECIFIC PRECIPITATION.
AB  - The addition of a water-clear extract of pneumococci to homologous antiserum
      produces a voluminous precipitate which carries down with it the agglutinins and
      practically the totality of the protective bodies against pneumococcus infection
      in animals. This precipitate when washed and resuspended in saline solution to
      the original volume of serum protects as well as the whole serum. The protein
      content of such solutions has varied from 0.09 to 0.34 per cent., as contrasted
      with about 6 per cent. in the original serum. The solution of this precipitate is
      not necessary to insure protection, and when produced by dilute alkali (sodium
      hydrate) frequently destroys the immune bodies.

PMID- 19867880
TI  - THE FACTORS OF COAGULATION IN THE EXPERIMENTAL APLASTIC ANEMIA OF BENZOL
      POISONING, WITH SPECIAL REFERENCE TO THE ORIGIN OF PROTHROMBIN.
AB  - 1. Subcutaneous injections of benzol in rabbits produce marked destructive
      changes in the hematopoietic organs, especially in the myeloid tissue. 2. Benzol
      poisoning registers a change not only in the formed elements of the blood, but
      also in the factors of coagulation. 3. The circulating prothrombin is
      considerably reduced in amount and in most instances animals in which such a
      diminution occurs show aplasia of the bone marrow. 4. The association of extreme
      aplasia of the marrow without a fatal diminution in the circulating prothrombin
      suggests one of two possibilities: either other tissues and organs in addition to
      the bone marrow are concerned with prothrombin formation; or a minimum amount of
      myeloid tissue suffices to maintain the quantity of prothrombin above a dangerous
      level.

PMID- 19867881
TI  - THE HISTOGENESIS OF CHRONIC URANIUM NEPHRITIS WITH ESPECIAL REFERENCE TO
      EPITHELIAL REGENERATION.
AB  - 1. Proliferation of connective tissue in chronic uranium nephritis is early and
      progressive and due to a direct stimulation on the part of the uranium. 2. The
      hydronephrotic theory fails to explain the phenomena observed in the progress of
      the chronic nephritis. 3. Carmine is deposited, as shown by Suzuki, in the
      proximal convoluted tubule only, and in different amounts in different levels of
      this segment of the tubule, so that subdivisions may be made. 4. Regeneration
      begins about the fourth day, but varies in proportion to the dose of renal
      irritant given. 5. The first cells to appear are large vesicular elements, and
      there is a gradual development of syncytium-like masses and giant-cells. These
      last are due to the rapidity of cell division. 6. Small, deeply staining nuclei,
      which are morphologically identical with the newly regenerated cells described by
      Thorel and others, are present from the first day of the acute nephritis and are
      persisting renal cells which have been slightly affected by the toxic agent.

PMID- 19867882
TI  - OBSERVATIONS ON THE ETIOLOGY OF GOITRE IN BROOK TROUT : IV. THE EFFECT OF FEEDING
      WITH FRESH AND STALE LIVER.

PMID- 19867883
TI  - THE ORIGIN AND STRUCTURE OF A FIBROUS TISSUE WHICH APPEARS IN LIVING CULTURES OF
      ADULT FROG TISSUES.
AB  - In living cultures of various kinds of adult frog tissues, which have been made
      according to the hanging drop method, there occurs, in many cases, a
      transformation of the plasma clot by which it becomes entirely changed from a
      typical fibrin net both in appearance and structure. The changes in the fibrin
      net generally begin when the culture is from two to three days old. During these
      changes it appears that the elements of the fibrin net fuse or consolidate, and
      as a result a great number of fine wavy fibrils are formed which unite to form
      wavy bundles of fibers, and these freely intertwine and anastomose as they ramify
      through the area of the plasma clot. The transformation of the fibrin net occurs
      first in the region of the clot which lies next to the imbedded tissue, gradually
      extends to the distal regions of the clot, and in time-as a rule in about two
      weeks-the entire plasma clot becomes changed from the fibrin net into a structure
      which to all appearances is identical with regular connective tissue. Photographs
      of both living and preserved cultures have been made to show the course of the
      transformation of the plasma clot and the development of the fibers. Experiments
      have been made which show that the fibers which are formed are not outgrowths of
      the imbedded tissue. Also they are not formed by an intracellular action, but
      arise directly by a transformation of the fibrin elements of the plasma clot.
      Experiments have been made which indicate that the transformation of the fibrin
      net will not occur unless it has come under the influence of living tissues or of
      living isolated cells. However, mechanical means, such as exerting tension on the
      clot with needles, may hasten the formation of the fibers. Also, in some
      cultures, movements of living isolated cells appear to aid in the formation of
      the fibers. The living tissues alone, however, are able to cause the fibers to
      form without the aid of any apparent mechanical factor. This is shown by cultures
      of various tissues in which no cell movement occurs and in which the plasma clot
      is undisturbed and yet a prolific formation of fibers may take place. Experiments
      have been made in order to determine the true nature of the transformed plasma
      clot and to see if the new fibrous tissue were still fibrin in character. The
      results that have so far been obtained from these tests have not been entirely
      conclusive and leave the question unsettled. The transformation of the fibrin net
      results in a shrinkage of the clot. It also becomes very tough and resistant to
      injury and, therefore, entirely different from the fragile and easily destroyed
      fibrin net when in its original condition. It is believed that such a reaction
      must play an important part in wound healing. A study of the relation between
      connective tissue fibers formed in wound healing and in embryonic development to
      the fibers formed in the plasma clot is being made, and the results will appear
      in a later paper.

PMID- 19867884
TI  - THE NATURE OF ANAPHYLATOXIN : STUDIES ON IMMUNITY. II.
AB  - 1. The union of fresh serum of pregnant or immunized animals with the
      corresponding boiled protein (substratum) is accompanied by the formation of
      poisonous substances. 2. The poison originates from the serum as a result of its
      autodigestion, and not from the substratum. 3. The process of autodigestion may
      be determined by the specific or non-specific removal of the antitrypsin of the
      serum. 4. The poisons originating from the serum are toxic only for homologous
      animals. 5. The autodigestion of the serum, if allowed to proceed far enough, may
      go beyond the toxic stage. 6. The biological properties of these poisons indicate
      their close similarity to the anaphylatoxin, and suggest that the anaphylatoxin
      of Friedberger is a product of the autodigestion of serum, and not of the protein
      outside of the serum.

PMID- 19867885
TI  - THE WIDE-SPREAD DISTRIBUTION OF DIPHTHEROIDS AND THEIR OCCURRENCE IN VARIOUS
      LESIONS OF HUMAN TISSUES.
AB  - It is evident from this work and from the work of others that organisms having
      diphtheroidal morphology are wide-spread in their distribution in the human body.
      They are readily isolated from miscellaneous skin lesions, probably thriving
      better in pathological soils as saprophytes than in normal skin, although they
      can be obtained quite easily from the latter. Various strains can also be
      cultivated from the air, at least in this environment. Aside from the air and
      superficial parts of the human body, diphtheroids have frequently been isolated
      from the deeper regions. Hoag, working on general paresis and certain conditions
      of the lung, cultivated 199 diphtheroids, the majority of which were from the
      lungs and respiratory tract, also in some instances from the liver and spleen. He
      considered 146 of these isolations to be identical and classified them as
      organism x. Robertson, McRae, and Jeffry likewise in cases of dementia paralytica
      isolated what they considered an identical strain which was closely related to
      the Klebs-Loeffler bacillus, from the inflamed ileum, stomach, tonsils or
      pharynx, bronchi, lung, and brain. They differentiated their organism from
      Bacillus hoffmanni and Bacillus xerosis. The fact that these organisms have a
      somewhat unusual morphology, resembling as they do an organism of known
      pathogenicity, namely. Bacillus diphtherioe, should form no basis for assuming
      that they, too, are apt to possess these qualities. When we consider the number
      of simple bacillary contaminators analogous to such organisms as Bacillus
      anthracis, Bacillus typhosus, etc., we can readily see how frequently this
      occurs. The majority of the diphtheroids isolated by us stai??? by Gram's method;
      nearly all fail to resist the standard acid-fast methods, although use of the
      very low strengths of mineral acids allows the fixed stain to remain in whole or
      in part. There is consequently nothing unique in their tinctorial properties.
      These bacillary strains differ considerably in their powers of cultivation. While
      the majority grow readily upon the ordinary laboratory foodstuffs, others require
      special products for their growth and still others cannot be grown even where
      special effort has been made. The fact that many strains grow slowly no doubt
      enhances their consideration as disease producers, as it seems to argue their
      difficult adaptation from their preexisting site to an artificial environment.
      This reasoning does not apply when we consider the numerous causal agents that
      can so readily be cultivated directly from the diseased tissue, and again the
      fact that many saprophytes in their natural habitat are incapable of growth in
      vitro (figure 1). The most striking of the biological features of these cultures
      is their wide range of pigment production. While many are white or creamy white,
      the majority range from a canary yellow to a distinct crimson, and one of the
      cultures recovered from a leper was a very deep dusky red or garnet. Numerous
      combined shades of yellow and pink, including such colors as salmon and orange,
      were present. Some cultures were distinctly pink, others varied in depth of color
      to a crimson. While many cultures of identical colors were obtained, the majority
      of strains showed some slight variance of shade. While, of course, the
      inoculation of diphtheroidal cultures produces varying degrees of localized
      inflammation if employed in sufficient dosage, probably for the two-fold reason
      of acting as a foreign body and liberating proteolytic substances, still the
      diphtheroids isolated in the past have never been able to reproduce the clinical
      picture of the various diseases from which they were cultivated. The apparent
      reproduction of lesions in general paresis, in hepatic cirrhosis, and in leprosy
      does not form an ultimate postulate for the acceptance of organisms as specific
      etiological entities. This is evidenced by the fact that certain known
      saprophytic organisms when used as controls are capable of producing the same
      results. It seems clear that organisms as broadly distributed as the diphtheroids
      should be suspected as contaminators when met in experiments bearing upon
      etiology. They should be viewed primarily in the same light as the staphylococcus
      and the various known contaminating bacteria. It is apparent that this type of
      organism has been regarded too much from the standpoint of pathogenicity. It is,
      of course, probable that among this large group there may be a few pathogenic
      types.

PMID- 19867886
TI  - DIFFUSION AND SURVIVAL OF THE POLIOMYELITIC VIRUS.
AB  - The ordinary virus of poliomyelitis present in aseptically removed brain tissue
      of paralyzed monkeys survives in an ascitic fluid kidney medium at the
      temperature of 37 degrees C. for a period of at least twenty, but not of thirty
      days. Under the conditions of moderate anaerobiosis, the minute microorganism
      cultivated from poliomyelitic tissues tends not to develop in cultures from the
      brain tissue; hence its presence does not complicate the survival test. The
      diffusion of the ordinary poliomyelitic virus from a noncomminuted fragment of
      brain tissue into a surrounding medium of ascitic fluid is so slight as not to be
      detectable by inoculation experiments conducted with usual quantities of the
      fluid. The specific effects of the microorganism cultivated from poliomyelitic
      tissues are not caused by an admixture in the cultures of the ordinary virus of
      poliomyelitis; hence they must be caused by the pathogenic action of the
      microorganism itself. The minute microorganism is therefore to be regarded as the
      specific microbic cause of epidemic poliomyelitis.

PMID- 19867887
TI  - THE RAPID PRODUCTION OF ANTIDYSENTERIC SERUM.
AB  - Antidysenteric serum can be safely prepared in the horse by the method of three
      successive intravenous injections of living cultures or toxin with intervening
      rest periods of seven days. When this method of immunization is employed, the
      specific antibodies responsible for agglutination and protection appear early and
      rise rapidly. By inoculating alternately living dysentery bacilli belonging to
      the Shiga and Flexner groups a polyvalent serum of high titer may be prepared. A
      polyvalent serum so produced should be suitable for the therapeutic treatment of
      acute bacillary dysentery, irrespective of the particular strain or strains of
      the dysentery bacillus causing the infection. An effective antidysentery serum
      suitable for therapeutic employment in man can be prepared in the horse in about
      ten weeks.

PMID- 19867888
TI  - A STUDY OF BARLOW'S DISEASE EXPERIMENTALLY PRODUCED IN FETAL AND NEW-BORN GUINEA
      PIGS.
AB  - 1. Pronounced cases of Barlow's disease may be produced in the fetus as early as
      ten to fifteen days after the commencement of dieting pregnant guinea pigs with
      oats and water. There are wide individual variations. The scorbutic changes in
      the skeleton are greatest in the earlier embryonic stages. The fetuses of that
      period, with practically no exceptions, die and show marked traces of impeded
      growth. 2. Fetuses from the later period of pregnancy are born alive, and
      apparently fully developed, with comparatively slight changes in the osseous
      system. 3. Even a short extension of the period of extra-uterine dieting on milk
      from scorbutic mothers and later on oats and water is sufficient to change the
      latent scurvy into a highly pronounced case. 4. The fetus cannot be kept alive
      longer than the adult animal, about twenty-eight days, either by intra-uterine
      dieting alone or by combined intra- and extra-uterine dieting. 5. The mothers
      show signs of disease at an early period, and are more severely attacked than non
      pregnant animals. Death also occurs comparatively often in the first period of
      gestation.

PMID- 19867889
TI  - PURE CULTIVATION IN VIVO OF VACCINE VIRUS FREE FROM BACTERIA.
AB  - Vaccine virus freed from all associated bacteria by means of suitable
      disinfecting agents can be propagated in a pure state in the testicles of rabbits
      and bulls. The virus cultivated in this manner is not only devoid of all
      bacteria, but appears capable of indefinite transfer from one animal to another.
      Sixty passages in rabbits of a pure strain have been made within one year.
      Several transfers from testicle to testicle are required to bring about accurate
      adaptation of the virus to the testicular parenchyma, so that continued
      propagation in this way can be certainly secured. During the first transfers from
      testicle to testicle the activity of the virus may be less than the original skin
      specimen from which the pure strain was derived; but as the transfers proceed the
      activity rises until, when the adaptation is complete, the activity of the
      testicular equals that of the skin strain. The multiplication of the virus within
      the testicle is maximum on the fourth or fifth day after inoculation; the
      quantity of virus remains about stationary until the eighth day, when diminution
      begins. At the expiration of five weeks no more virus could be detected in the
      testicle. The vaccinal processes in the skin, cornea, and testicle of rabbits are
      practically identical whether the virus employed for the inoculation has been the
      original skin strain or the pure testicular strain; and the skin lesions produced
      in the calf with the two strains are also identical. In conformity with the
      finding mentioned in the last paragraph it has been found that human beings react
      to the pure testicular strain of vaccine virus in an entirely typical manner. In
      the case both of original vaccination and revaccination the vaccinal effects
      cannot be distinguished from those arising from uncomplicated skin virus. Pure
      strains of testicular virus are readily produced, and once secured they may be
      propagated in a pure state by the method described in rabbits or bulls without
      difficulty and with economy. The pure strains thus obtained should supply an
      ideal form of virus for employment in the vaccination of human beings.

PMID- 19867890
TI  - THE TRANSPLANTATION OF TUMORS TO FOREIGN SPECIES.
AB  - By feeding to rats the tissue of the mouse chondroma they are rendered more
      suitable as hosts for the growth. Using this method rats have been inoculated
      successfully with the mouse tumor and it has been transferred to three successive
      series of these animals.

PMID- 19867891
TI  - THE EFFECT OF ARSENIC COMPOUNDS ON THE ROUS CHICKEN SARCOMA.
AB  - Arsenic and arsenious acids, cacodylic acid, atoxyl, and neosalvarsan fail to
      influence markedly the growth of the Rous chicken sarcoma.

PMID- 19867892
TI  - ANTIBODY FORMATION AGAINST TREPONEMA PALLIDUM-AGGLUTINATION.
AB  - It has been shown by our experiments that the serum of rabbits treated with
      emulsions of Treponema pallidum contains agglutinating substances. Normal rabbit
      serum also possesses agglutinating power for this organism, but, as in the case
      of normal bacterial agglutinins, to an extent very much inferior to that
      possessed by the sera of immunized animals. Normal human sera will agglutinate
      similar pallidum emulsions, as will the sera of certain syphilitic patients with
      positive Wassermann reactions. Whether or not there is a quantitative difference
      of diagnostic value between the sera of normal human beings and those of
      syphilitics remains to be seen. The sera of rabbits immunized with strain A
      agglutinate Noguchi's strain 9 in dilutions as high as 1 to 500. We regard as the
      most important result of these experiments the demonstration of definite
      antibodies in the circulation of animals treated with dead emulsions of Treponema
      pallidum. Since it is our belief that the agglutinating effect is due to an
      antibody essentially the same as that which produces bactericidal, precipitating,
      and opsonic effects, i. e., that there is probably one type of antibody only, we
      believe that the demonstration of agglutinins establishes the fact that in
      syphilis as in bacterial diseases the host responds by the formation of
      antibodies or sensitizers specific for the treponema. Spirocheticidal experiments
      with these sera, both in vitro and in vivo, are in progress.

PMID- 19867893
TI  - ADULT TERTIAN MALARIAL PARASITES ATTACHED TO PERIPHERAL CORPUSCULAR MOUNDS. THE
      EXTRACELLULAR RELATION OF THE PARASITES TO THE RED CORPUSCLES.
AB  - 1. The malarial parasite is extracellular throughout its entire life cycle; that
      is, when it is not free in the blood serum, it is attached to the external
      surface of the red corpuscle. 2. Adult parasites follow the same procedure in
      attaching themselves to the outer surface of the red corpuscles as do the young
      parasites. 3. Adult parasites are most frequently seen attached to surface
      corpuscular mounds. 4. Corpuscular mounds projecting at the periphery of the red
      corpuscles and encircled by the pseudopodia of adult parasites, are proof
      positive of the extracellular relation of the adult parasite to the red
      corpuscle. 5. Adult parasites attached to peripheral corpuscular mounds are only
      found in appreciable numbers when the red corpuscles are not badly damaged, so
      that the mounds show more or less hemoglobin content. 6. The nuclei or protoplasm
      of adult parasites extending beyond the periphery of the red corpuscles is
      additional evidence of the extracellular relation of the parasites to the red
      corpuscle.

PMID- 19867894
TI  - THE INFLUENCE OF DIGITALIS ON THE T WAVE OF THE HUMAN ELECTROCARDIOGRAM.
AB  - It has been shown in this investigation that digitalis, administered orally to
      patients, can modify the T wave in the electrocardiogram. When the T wave in the
      initial curve is directed upward, the first change noticed is a lowering, and the
      final change is an inversion of the wave. It is not only the wave itself, but
      that portion of the curve between the end of R and the end of T which is
      involved. Instances in which the initial T waves have other than upright forms
      are described and their behavior under the influence of digitalis has been
      indicated. This influence of digitalis on the T wave may be detected in thirty
      six to forty-eight hours after the administration of digitalis has commenced; it
      may persist as long as twenty-two days after the administration has been stopped.
      Instances where it persisted only five days have been encountered. The unexpected
      length of duration of the sign probably explains why a second treatment with
      digitalis requires a smaller amount of the drug to produce the same effect, than
      the first.

PMID- 19867895
TI  - A STUDY OF THE EFFECT OF SENSITIZATION ON THE DEVELOPMENT OF THE LESIONS OF
      EXPERIMENTAL PNEUMONIA IN THE RABBIT.
AB  - While preliminary treatment with culture filtrates or dead cells of the extremely
      virulent strain A gave rise to varying degrees of immunity, the exudative lung
      lesions developing after tracheal injection with live organisms of the same
      virulent strain were not strikingly increased in any group or series of these
      rabbits. Despite carefully graduated dosage in the preliminary treatment, none of
      the animals developed symptoms of a definitely anaphylactic nature. In similar
      experiments following sensitization with the attenuated avirulent culture AA,
      tracheal injection of virulent or avirulent organisms of the same strain failed
      to incite any definite increase in the exudative lung reaction. In none of the
      rabbits were symptoms resembling anaphylaxis noted. The immunity which was
      induced by the larger sensitizing doses of culture filtrates of the strain in the
      virulent state was lacking when similar doses of the culture filtrates of
      organisms in the non-virulent state were used. Extensive lesions developed in
      both sensitized and unsensitized rabbits when the strain used in the tracheal
      injection was one apparently combining moderate virulence with exceptional
      toxicity, indicating that the exudative lung reaction was one of adjustment
      rather than of acquired hypersusceptibility. When, in the experiments, small
      amounts of sera from normal rabbits, or from animals immunized to culture
      filtrates, were added to the culture before tracheal injection, an increased
      fibrinous lung reaction was frequently found. The present study would seem to
      give some ground for the view that while in pneumonia a hypersensitive condition
      probably takes some part in the inception of the infection, the subsequent
      development of the diffuse exudative reaction in the lung is not directly due to
      an acquired hypersusceptibility, but to intrinsic qualities possessed by the
      pneumococcus itself. This study was carried on in the Department of Bacteriology
      of the College of Physicians and Surgeons of Columbia University, New York, and
      later, through the courtesy of Dr. Charles Norris, in the Bellevue Hospital
      Laboratories. It was completed in the Laboratories of the New York State
      Department of Health at Albany. I am greatly indebted to Dr. Augustus Wadsworth
      for his advice and criticism.

PMID- 19867896
TI  - THE VISUAL CORTEX, ITS LOCALIZATION, HISTOLOGICAL STRUCTURE, AND PHYSIOLOGICAL
      FUNCTION.
AB  - In the study of the human cortex it seems well to follow the same primary
      divisions for the entire cortex, while in certain areas some layers may assume
      certain modifications; viz., in the area striata it seems clearer to retain the
      sixth layer ground type, of which the fourth is subdivided into three secondary
      layers. The visual cortex, on account of its relation to the act of seeing, is an
      especially interesting field for study. About the calcarine fissure one can
      readily see with the naked eye a stripe of white fibers lying in the gray
      substance, called stria of Gennari or of Vicq-d' Azyr. This layer is considered
      by Brodmann in the second subdivision of the fourth primary layer. The two most
      characteristic types of the cortex are the giant pyramid type, called area
      gigantopyramidalis, and the calcarine type, called area striata. The higher types
      of mammals afford excellent material for comparison. Minkowski's experimental
      study of the dog indicates that the clinical, anatomical visual sphere is covered
      with the cytoarchitectonic sphere; for lasting visual trouble can be caused only
      by extirpation of the area striata. The subcortical visual center in mammals
      undergoes secondary degeneration through destruction of the area striata, and
      therefore depends on the cortex. Also certain parts of the corpus geniculatum
      externum have an exact projection over certain areas of the cortex.

PMID- 19867897
TI  - A STUDY OF THE PATHOGENIC PROPERTIES OF BACILLUS PROTEUS.
AB  - Some strains of Bacillus proteus obtained from human lesions are pathogenic for
      rabbits, rats, and guinea pigs. There is good evidence that these strains are
      also pathogenic for man. All cultures obtained from sources other than human
      infections were non-pathogenic for the laboratory animals. A non-pathogenic
      culture may be made pathogenic by the use of aggressins or by inoculation into
      the anterior chamber of the eye. Proteus cultures lose their virulence rapidly
      when grown on artificial media. The lesions produced in animals are either simple
      abscesses, proliferative lesions, or a mixed exudative and proliferative lesion.
      The proliferative lesions consist mainly of epithelioid cells apparently of
      connective tissue origin. No giant-cells of the Langhans type are present. The
      histological type of the lesion does not depend upon the strain employed. Neither
      does it bear any relation to the clinical severity of the case. The ability to
      produce the characteristic lesions has no necessary connection with the toxicity
      of the bacteria. The proteus bacteria probably play a more important part in
      human pathology than is generally believed.

PMID- 19867898
TI  - STUDIES ON THE CIRCULATION IN MAN : XII. A STUDY OF INEQUALITIES IN THE BLOOD
      FLOW IN THE TWO HANDS (OR FEET) DUE TO MECHANICAL CAUSES (EMBOLISM, COMPRESSION
      OF VESSELS, ETC.) OR TO FUNCTIONAL (VASOMOTOR) CAUSES, WITH A DISCUSSION OF THE
      CRITERIA BY WHICH THE CONDITIONS ARE DISCRIMINATED.
AB  - 1. In cases in which great inequalities in the blood flow in the two hands were
      produced by mechanical causes (ligation or compression of vessels, embolism), the
      stability of the ratio of the flows, in successive measurements at short
      intervals, was found to be characteristic. Over long intervals the opening up of
      collateral circulation or the progressive increase of the block (in a case of
      multiple embolism with thrombosis) was followed by changes in the ratio of the
      blood flows in the normal and the affected part. Another criterion of these
      conditions was found to be that the inequality was not abolished by producing
      general vasomotor changes; e. g., by altering the external temperature. 2. In
      certain cases inequalities in the blood flow in the two hands (or feet) were
      found which were not stable from day to day, and which could be abolished,
      reduced, increased, or reversed by alterations in the external conditions which
      bring about general vasomotor changes. These inequalities, not associated with
      clinically recognizable differences between the parts compared, were interpreted
      as due to unequal activity of the vasomotor mechanism on the two sides. The
      condition appeared to be most frequent in certain groups of neurological cases.

PMID- 19867899
TI  - THE OCCURRENCE OF CARRIERS OF DISEASE-PRODUCING TYPES OF PNEUMOCOCCUS.
AB  - Lobar pneumonia in 75 per cent of instances is due to specific types of
      pneumococci possessed of a high degree of pathogenicity. Although pneumococci
      occur in the mouths of 60 per cent of normal individuals, such organisms are
      readily distinguishable from the highly parasitic types of pneumococcus
      responsible for the severe forms of lobar pneumonia, a convincing proof that
      infection in this disease is, in the majority of instances, not autogenic in
      nature, but is derived from some extraneous source. In a high percentage of
      instances healthy persons intimately associated with cases of lobar pneumonia
      harbor the disease-producing types of pneumococcus. In every such instance the
      pneumococcus isolated has corresponded in type with that of the infected
      individual. Convalescents from pneumonia carry for a considerable length of time
      the type of pneumococcus with which they have been infected. The existence of the
      carrier state among healthy persons and among those recently recovered from
      pneumonia establishes a basis for understanding the mechanism by means of which
      lobar pneumonia spreads and maintains its high incidence from year to year.

PMID- 19867900
TI  - FURTHER EXPERIMENTS ON THE EFFECTS OF LONG CONTINUED INTRAPERITONEAL INJECTIONS
      OF PROTEINS.
AB  - We have attempted to discover whether or not certain protein materials, such as
      albumose, casein, and albumen, when introduced parenterally (peritoneally) into
      experimental animals, are able to produce organic lesions. These proteins were
      used alone or in combination with chloroform, which was administered in oil and
      as an anesthetic. Our results were negative.

PMID- 19867901
TI  - HIBERNATION AND THE PITUITARY BODY.
AB  - A train of symptoms, coupled with retardation of tissue metabolism and with
      inactivity of the reproductive glands, not only accompanies states of
      experimentally induced hypophysial deficiency, but is equally characteristic of
      clinical states of hypopituitarism. The more notable of these symptoms are a
      tendency, in the chronic cases, toward an unusual deposition of fat, a lowering
      of body temperature, slowing of pulse and respiration, fall in blood pressure,
      and oftentimes a pronounced somnolence. These symptoms bear a marked resemblance
      to the physiological phenomena accompanying the state of hibernation which have
      heretofore been unsatisfactorily ascribed solely to extracorporeal factors;
      namely, a seasonal deprivation of food and low temperature. In a series of
      hibernating animals (woodchucks) it has been found that during the dormant period
      histological changes are apparent in many of the ductless glands. The most
      notable of these changes occur in the pituitary body, as previously observed by
      Gemelli. The gland not only diminishes in size, but the cells of the pars
      anterior in some animals at least completely lose their characteristic staining
      reactions to acid and basic dyes. At the end of the dormant period the gland
      swells, and as the cells enlarge they again acquire their differential affinity
      for acid, basic, and neutral stains, and at the same time karyokinetic figures
      may appear.

PMID- 19867902
TI  - LATE POISONING WITH CHLOROFORM AND OTHER ALKYL HALIDES IN RELATIONSHIP TO THE
      HALOGEN ACIDS FORMED BY THEIR CHEMICAL DISSOCIATION.
AB  - The central lobular necrosis in the liver, which has been regarded by some
      writers as characteristic of late chloroform poisoning, has been produced
      experimentally with a number of other drugs. It is, therefore, in no sense
      peculiar to chloroform poisoning. Substances which have been shown to produce a
      morphological picture indistinguishable from that of late chloroform poisoning
      are: (a) dichlor- and tetrachlormethane, (b) tribrom- and triiodomethane, (c)
      monochlor-, monobrom-, and monoiodoethane, also the dibromethane; that is, in
      general, the halogen substituted aliphatic hydrocarbons containing one or two
      carbon atoms. Presumably similar results might be obtained with the higher
      members of the same series. The mechanism by which chloroform produces its
      characteristic tissue changes must accordingly be considered as a group reaction.
      Outside the body the similarities between the chemical behavior of different
      members of this group have been correlated by Nef on the basis of the type of
      dissociation which these substances undergo and the differences in their behavior
      on the basis of the differences of the degree to which such dissociations occur.
      According to the work of Nef, the group of substances under discussion has the
      property of dissociating to yield a halogen acid and an unsaturated alkylidene
      rest. Thus with chloroform the type of dissociation may be expressed thus: See
      PDF for Equation In this paper the view is developed that the changes
      characteristic of late poisonings with the above named group, namely edema,
      multiple hemorrhages, fat infiltration, and necrosis are ascribable (1) to acids
      and (2) to the fact that the amount of acid formed parallels the chemical
      dissociability of the drug outside of the body. Favoring the view that acid is
      responsible for the changes are the following observations. 1. All the
      characteristic features of late chloroform poisoning have been produced merely by
      the administration of hydrochloric acid, except, however, for a different
      distribution of the liver necrosis. 2. The areas of central necrosis produced in
      the liver by the various substances under discussion give an acid reaction to
      neutral red. 3. Sodium carbonate in a hypertonic sodium chloride solution
      markedly inhibits the production of the lesions.

PMID- 19867903
TI  - THE FORM OF THE EPITHELIAL CELLS IN CULTURES OF FROG SKIN, AND ITS RELATION TO
      THE CONSISTENCY OF THE MEDIUM.
AB  - 1. Fragments of skin from the leopard frog (Rana pipiens) were cultivated in
      media of varying consistency. A mixture of frog plasma, frog muscle extract,
      chicken plasma, and chicken embryo extract usually produced a very firm medium; a
      mixture of frog plasma, frog muscle extract, and chicken plasma, one less firm
      (semi-firm); and a mixture of frog plasma and frog muscle extract a medium of a
      consistency varying from soft to liquid. 2. (a) In a firm medium the cells which
      migrate into the medium are polyhedral (polygonal when seen from above) in form,
      which shape they retain permanently. They remain united in a compact membrane,
      the central parts of which consist of several (three to four) layers of cells.
      Migration of isolated cells into the medium does not take place. (b) In the semi
      firm media the cells situated at the edge of the membrane become fusiform in
      shape, gradually detach themselves from the membrane, and stray out individually
      into the medium. This causes the membrane to become loose in character, and to
      contain holes, while its edges at the same time become very irregular and send
      out pointed projections. (c) In a soft medium the cells are fusiform or thread
      like in shape. The migration of isolated cells is much more pronounced than in
      the semi-firm media, as a result of which the membrane undergoes constant and
      rapid loosening up. By this means whole portions of the membrane become detached
      and their separate parts are at first united by the thread-like columnar cells,
      which become drawn out in the form of long threads upon the separation of the
      individual sections of the membrane. The loosening up of the membrane is further
      assisted by liquefaction and the consequent formation of vacuoles; the latter
      process likewise results in the formation of thread-like columnar cells. (d)
      Liquid media contain only round cells. 3. This serves to explain numerous
      internal processes of the organism, especially certain changes of form observed
      by Leo Loeb in transplantations of wound scabs and of skin; the conditions
      artificially produced by Leo Loeb must have effected a change in the consistency
      of the medium. 4. It has been shown that it is unnecessary, for a satisfactory
      explanation of the above findings, to have recourse to the theories of
      "functional stimulus" or "inhibiting influences," by means of which Champy wished
      to account for the variations in the morphological character of the cells.

PMID- 19867904
TI  - THE HEART MUSCLE IN PNEUMONIA.
AB  - 1. The heart muscle is not functionally impaired in pneumonia, since the
      pneumonic ventricle beats normally as soon as its food is normal. 2. Pneumonic
      blood, suddenly fed to normal heart muscle, lowers its efficiency, lessening the
      duration and the area of contraction. 3. The heart muscle in pneumonia, exposed
      gradually to the action of the poison, largely adjusts itself to its poisoned
      food.

PMID- 19867905
TI  - SERUM FERMENTS AND ANTIFERMENT AFTER FEEDING : STUDIES ON FERMENT ACTION. XXI.
AB  - 1. After feeding, an increase in non-coagulable nitrogen of the serum can be
      determined, reaching a maximum in about six hours. 2. This increase is greatest
      in the portal blood and is partially due to an increase in amino-acids. There is
      no increase in proteoses. 3. There is usually a progressive decrease in serum
      protease, reaching a minimum after from five to seven hours. 4. The portal blood
      may show an unaltered or an increased amount of protease. 5. The serum
      antiferment shows a slight increase, but is subject to considerable fluctuation.
      6. The serum lipase (esterase) shows a slight increase, reaching a maximum after
      three hours. The hepatic blood usually contains the lowest concentration of
      lipase.

PMID- 19867907
TI  - THE IMMUNOLOGICAL RELATIONS OF THE ROUS CHICKEN SARCOMA.
AB  - The injection of chicken embryo, in amounts of from 1 to 10 cc., confers no
      resistance against the Rous chicken sarcoma, when this is inoculated from 5 to
      100 days after the preliminary treatment.

PMID- 19867906
TI  - SERUM FERMENTS AND ANTIFERMENT DURING TRYPSIN SHOCK : STUDIES ON FERMENT ACTION.
      XXII.
AB  - 1. The intravenous injection of trypsin in dogs results in a shock similar in
      many respects to anaphylactic and peptone shock. 2. The injection is followed by
      a marked rise of serum protease and lipase. 3. The antiferment usually shows a
      distinct drop in titer, with a recovery following in from four to twenty-four
      hours. 4. The non-coagulable nitrogen shows no constant alteration, but is never
      greatly changed in amount. 5. Inactivated preparations were in some respects
      followed by symptoms similar to those following the injection of the active
      preparation. 6. Subcutaneous and gastric absorption was practically without
      effect. 7. Intestinal absorption was followed by an increase in serum protease
      without evidence of intoxication, or by typical symptoms of acute poisoning. 8.
      The leucocyte curve bears no constant relation to the serum protease or lipase.

PMID- 19867908
TI  - CASTRATION EXERTS NO INFLUENCE UPON THE GROWTH OF TRANSPLANTED OR SPONTANEOUS
      TUMORS IN MICE AND RATS.
AB  - Castration neither increases nor decreases the inoculation percentage of
      transplantable carcinomata and sarcomata of the mouse and rat, nor does it either
      stimulate or retard their proliferation; it exerts not the slightest effect upon
      the growth of spontaneous carcinomata of the mouse.

PMID- 19867909
TI  - INFLAMMATORY REACTIONS IN RABBITS WITH A SEVERE LEUCOPENIA.
AB  - Congestion of blood vessels and marked edema may occur in rabbits with a severe
      leucopenia. These two phenomena are, therefore, independent of the leucocytes.

PMID- 19867910
TI  - THE ARTIFICIAL PRODUCTION IN MAMMALIAN PLASMA OF SUBSTANCES INHIBITORY TO THE
      GROWTH OF CELLS.
AB  - Active immunity to the growth of tissue may be obtained by intraperitoneal
      injections of tissue emulsions. This immunity is of short duration and is
      followed by an anti-immunity. The immunity varies for individual tissues both in
      extent and in the time of onset. The immunity is not specific in so far that it
      is not more marked to the tissue similar to that forming the emulsion.

PMID- 19867911
TI  - THE LYMPHOCYTE IN NATURAL AND INDUCED RESISTANCE TO TRANSPLANTED CANCER : II.
      STUDIES IN LYMPHOID ACTIVITY.
AB  - The refractory state to transplanted cancer, induced by the subcutaneous
      injection of defibrinated blood, is accompanied in every case by a definite
      lymphoid crisis in the blood. The rise of lymphocytes is not present during the
      interval between the immunizing injection and the cancer inoculation but comes on
      sharply within twenty-four hours of the introduction of the cancer graft. In
      control animals where the graft leads to a definite take there is no such
      lymphoid response, but in instances of natural immunity the phenomenon is similar
      to that seen in artificially induced immunity, though the period of rise is often
      delayed for several days or a week. The lymphoid crisis is not merely an
      accompanying factor in the immune period; it is essential to the process. This is
      demonstrated by the fact that destruction of the lymphocytes by x-ray is
      accompanied by the loss of natural or induced resistance to the growth of
      inoculated cancer. The polymorphonuclear cells show a tendency to increase in the
      animals with growing tumors, but further study will be necessary before any
      conclusions regarding them can be drawn.

PMID- 19867912
TI  - THE NUMERICAL LAWS GOVERNING THE RATE OF EXCRETION OF UREA AND CHLORIDES IN MAN :
      I. AN INDEX OF UREA EXCRETION AND THE NORMAL EXCRETION OF UREA AND CHLORIDES.
AB  - 1. The excretion of urea and of chlorides in the normal individual is carried out
      according to definite laws, capable of numerical expression. 2. The rate of
      excretion of urea and of sodium chloride is determined by the concentration in
      the blood, the rate of water output, and indirectly by the weight of the
      individual. 3. The threshold of sodium chloride excretion is practically constant
      at about 5.62 grams of sodium chloride per liter of plasma. Slight variations in
      the threshold occur in normal individuals. 4. The rate of excretion of urea under
      the conditions found at any time can be measured directly in terms of the normal
      by an index of urea excretion.

PMID- 19867913
TI  - EXTIRPATION OF THE PINEAL BODY.
AB  - 1. Following the removal of the pineal I have observed no sexual precocity or
      indolence, no adiposity or emaciation, no somatic or mental precocity or
      retardation. 2. Our experiments seem to have yielded nothing to sustain the view
      that the pineal gland has an active endocrine function of importance either in
      the very young or adult dogs. 3. The pineal is apparently not essential to life
      and seems to have no influence upon the animal's well being.

PMID- 19867914
TI  - THE CONCENTRATION OF THE PROTECTIVE BODIES IN ANTIPNEUMOCOCCUS SERUM. SPECIFIC
      PRECIPITATE EXTRACTS.
AB  - 1. The protective substances contained in specific precipitates from
      antipneumococcus serum can be extracted by suitable chemical and physical agents,
      dilute sodium carbonate at 42 degrees C. being especially advantageous as an
      extractive agent. 2. The resulting water-clear extracts, when made up to the
      original volume of the serum used for precipitation, protect animals almost as
      well as does the whole serum. 3. The bacterial extracts used in precipitating the
      protective substances from the serum act specifically; that is, a bacterial
      extract of pneumococcus of Type I removes the protective substances from a Type I
      immune serum only. 4. In a polyvalent serum of Type I and Type II, the protective
      substances of each type may be removed independently of each other by the
      successive addition of the homologous antigens. 5. Extracts of specific serum
      precipitates contain only one-fiftieth to one-sixtieth of the protein in the
      original serum, and about one-half the protein of the whole precipitate. 6.
      Extracts contain not only protective substances but agglutinins and precipitins.
      7. Extracts and whole precipitates not only confer passive immunity but stimulate
      the production of active immunity to pneumococcus infection in rabbits and mice.

PMID- 19867915
TI  - THE ACTION OF ETHYLHYDROCUPREIN (OPTOCHIN) ON TYPE STRAINS OF PNEUMOCOCCI IN
      VITRO AND IN VIVO, AND ON SOME OTHER MICROORGANISMS IN VITRO.
AB  - 1. Ethylhydrocuprein hydrochloride in very high dilution inhibits the growth of,
      and in 18 hours kills, representatives of all four groups of pneumococci in
      vitro. The killing effect is generally seen in somewhat lower dilutions than the
      inhibiting effect. No constant or considerable difference is seen in these
      actions on representatives of the four groups of the pneumococci. The action of
      ethylhydrocuprein hydrochloride on the pneumococci in vitro is so strongly
      specific that it may possibly be used as a test for a true pneumococcus. 2. The
      inhibitory or killing effects of ethylhydrocuprein hydrochloride in vitro on
      bacteria other than pneumococci are slight or absent. The effects are greater on
      streptococci than on any other organisms examined, but are still much less than
      on the pneumococci. This action distinguishes between the streptococcus group,
      including Streptococcus mucosus sometimes found in normal mouths, on the one
      hand, and the true pneumococcus (including Pneumococcus mucosus), on the other.
      3. Quinine hydrochloride inhibits the growth of, and kills the pneumococcus in
      vitro; much stronger concentrations, however, are necessary than in the case of
      ethylhydrocuprein. This effect of quinine hydrochloride is also seen on other
      organisms, but in a less degree. 4. Ethylhydrocuprein (optochin base) has a well
      marked protective action against experimental pneumococcal infection in mice in
      the case of type strains of all four groups of pneumococci; this protective
      action may be efficient against many multiples of the minimum lethal dose.

PMID- 19867916
TI  - THE EFFECT OF IRRITATION ON THE PERMEABILITY OF THE MENINGES FOR SALVARSAN.
AB  - The subdural injection of normal salt solution, normal serum, serum salvarsanized
      in vivo or weak solutions of cyanide of mercury does not demonstrably increase
      the permeability of the spinal cord or brain for salvarsan which is circulating
      in the blood at the time of the subdural injection.

PMID- 19867917
TI  - CHANGES IN THE ELECTROCARDIOGRAMS ACCOMPANYING EXPERIMENTAL CHANGES IN RABBITS'
      HEARTS.
AB  - 1. In rabbits transient and also permanent enlargements of the heart occur as the
      result of the intravenous injection of adrenalin, spartein and adrenalin,
      diphtheria toxin, and streptococci. 2. Transient and permanent enlargements of
      the heart to the left are associated with decrease in the size of the upwardly
      directed waves of the Q, R, S group in Lead II of the electrocardiograms and
      increase in the downwardly directed. Transient enlargement to the right is
      associated with changes in the opposite direction. 3. The stages in the process
      of enlargement have been observed and are associated with gradual changes in the
      size of these waves. 4. A diminution in the size of all the waves of the Q, R, S
      group was observed in degenerative conditions of the heart muscle. 5. Extreme
      degeneration of the structures of the heart was associated with slowing of the
      heart's action, lengthening of conduction time (P-Q), and lengthening of the time
      occupied by the individual waves of the electrocardiogram. 6. Ectopic ventricular
      contractions were seen in rabbits injected intravenously with suspensions of
      living streptococci.

PMID- 19867918
TI  - BACTERIOLOGICAL AND CLINICAL STUDIES OF AN EPIDEMIC OF KOCH-WEEKS BACILLUS
      CONJUNCTIVITIS ASSOCIATED WITH CELL INCLUSION CONJUNCTIVITIS.
AB  - 1. There are cases in which epithelial cell inclusions may alone be present in
      the conjunctival smears. In such cases no other pathogenic organisms, such as the
      Koch-Weeks bacillus or the pneurnococcus, can be demonstrated in smears or
      cultures. 2. The conjunctiva can become simultaneously infected with the
      inclusion bodies and Koch-Weeks bacilli or other organisms. 3. In cases of acute
      or subacute conjunctival inflammations due to mixed infections the clinical
      features of each infection may be present. The course of the inflammation is,
      however, more prolonged. 4. Within recent years, the Koch-Weeks bacillus has only
      seldom been found in our routine examinations. 5. The epidemic studied was of a
      severe type. 6. Clinically it is practically impossible to distinguish
      pneurnococcal conjunctivitis from the Koch-Weeks conjunctivitis. Bacteriological
      examination of smears and cultures is the only means by which the etiological
      diagnosis can be definitely established. 7. Conjunctivae of certain species of
      monkeys are susceptible to the von Prowazek inclusion bodies, but not to the
      hemoglobinophilic bacilli isolated from cases of epidemic conjunctivitis. 8. The
      injection of conjunctival scrapings containing the von Prowazek cell inclusions
      into the testicles of rabbits produces no cell inclusions in the latter, while
      the injection of a pure culture of the hemoglofcinophilic bacilli causes an acute
      inflammation accompanied by numerous clumps of the organisms, simulating the von
      Prowazek bodies at certain stages of their evolution. 9. There exists an apparent
      morphological similarity between the degenerated forms of this variety of the
      hemoglobinophilic bacilli and the cell inclusions, both in cultures and in
      experimental orchitis in the rabbit. But, as a rule, the elementary bodies of the
      latter are much smaller and more sharply defined than the smallest granules of
      the former, while the initial bodies are bigger, more intensely stainable, and
      less definite in their contour than the hemoglobinophilic bacilli found in the
      infected conjunctivae.

PMID- 19867919
TI  - STUDIES OF METABOLISM IN THE DOG BEFORE AND AFTER REMOVAL OF THE SPLEEN.
AB  - Four dogs have been subjected to metabolism studies before splenectomy and at
      intervals of three days to three months after splenectomy. In three of the four
      animals the removal of the spleen was not followed by any disturbances of
      nitrogen metabolism, fat utilization, or iron elimination. Two of these animals
      showed no anemia, and the third only a slight reduction in hemoglobin and number
      of red cells. A fourth animal, studied ten days and three months after
      splenectomy, developed eventually a definitely progressive anemia of moderate
      severity. This animal showed a slight loss of weight, a slight disturbance of
      nitrogen balance, and of creatine-creatinine partition, with a marked increase in
      the elimination of iron. We conclude therefore that the spleen has no important
      influence on metabolism, and that the disturbances occurring in one of our dogs
      were due to the coexisting anemia and not to the absence of the spleen.

PMID- 19867920
TI  - STUDIES IN LIVER AND KIDNEY FUNCTION IN EXPERIMENTAL PHOSPHORUS AND CHLOROFORM
      POISONING.
AB  - 1. We have confirmed the results of previous workers on tetrachlorphthalein,
      fibrinogen, and lipase. 2. The total non-protein nitrogen, urea, and amino-acids
      of the blood serum show a definite and sometimes marked increase in phosphorus
      poisoning. These changes are not so evident in chloroform poisoning, although
      they sometimes occur. They are usually terminal phenomena. 3. The urinary
      nitrogen partition between the urea, ammonia, and amino-acids is not always
      disturbed. The most important changes which occur are an increased amino nitrogen
      in chloroform and phosphorus poisoning, and a very low urea nitrogen percentage
      in severe fatal chloroform poisoning. 4. Sugar tolerance towards galactose and
      levulose is in general markedly decreased in both types of poisoning. 5. In
      phosphorus poisoning liver functional changes can and do occur without
      concomitant renal changes. Renal insufficiency usually arises as a terminal
      event. 6. Increased nitrogenous products in the blood (total non-protein
      nitrogen, urea, and amino nitrogen) are associated with an increase of these
      bodies in the urine. Consequently, an increased protein catabolism, as well as
      renal insufficiency, is necessary to explain this accumulation. 7. A terminal
      acidosis, as evidenced by increased hydrogen ion concentration in the blood,
      usually occurs.

PMID- 19867921
TI  - THE INTOXICATION OF SPLENECTOMIZED MICE BY FEEDING FRESH SPLEEN AND OTHER ORGANS.
AB  - The intoxication which is developed when splenectomized mice are fed with fresh
      spleen is more regular in occurrence when the feeding experiment is carried out
      four or five days after splenectomy than when it is done at later periods. The
      intoxication is easily recognizable even in its less severe forms by a
      lengthening of the coagulation time of the blood. An intoxication of the same
      character is produced when splenectomized mice are fed with the mucous membrane
      of the stomach and upper small intestine. Bone marrow and dried blood probably
      give the same reaction in a somewhat milder form. The other organs either give no
      intoxication at all when fed, or in certain instances the thyroid, adrenal, and
      salivary gland (mouse) give intoxications of a different character which affect
      intact mice and splenectomized animals equally. The spleen or the gastro
      intestinal mucosa is equally effective in producing the intoxication, whether it
      be derived from heterologous or homologous species. Certain experiments, not
      reported in detail, indicate that the susceptibility to the intoxication
      disappears in time and that this time may be shortened by repeated feedings with
      sublethal amounts of organ substance.

PMID- 19867922
TI  - THE FUNCTION OF THE SPLEEN IN THE EXPERIMENTAL INFECTION OF ALBINO MICE WITH
      BACILLUS TUBERCULOSIS : THIRD PAPER.
AB  - Experiments are reported which show that in all probability the increased
      resistance to tuberculous infection which is imparted to mice by the removal of
      the spleen is a consequence of the loss of a function of the organ. This function
      can be restored by the feeding of fresh spleen. For the present we attribute
      these changes to the removal and restoration, as the case may be, of a particular
      substance for which the designation tuberculosplenatin is suggested. This
      substance is assumed to be related to the spleen as adrenalin is related to the
      adrenal gland. It is peculiar to the organ but not to the species. It is not
      found in other organs of the body so far as our observations have extended. The
      absence of the substance from the lymphatic glands seems of especial importance
      in this connection.

PMID- 19867923
TI  - THE NUMERICAL LAWS GOVERNING THE RATE OF EXCRETION OF UREA AND CHLORIDES IN MAN :
      II. THE INFLUENCE OF PATHOLOGICAL CONDITIONS AND OF DRUGS ON EXCRETION.
AB  - A method of measuring the rate of excretion of urea, in terms of the normal, as
      presented in a preceding paper, has been applied to the study of diseased
      conditions and of the action of drugs. Simultaneous observations on chloride
      excretion have been made by comparing the concentration of chlorides actually
      found in the plasma with the theoretical amount, calculated from the rate of
      excretion. Observations made in this way have been found applicable to the study
      of various diseased conditions.

PMID- 19867924
TI  - THE CHEMOSEROTHERAPY OF EXPERIMENTAL PNEUMOCOCCAL INFECTION.
AB  - 1. A single small dose of ethylhydrocuprein (optochin base), which by itself has
      practically no protective effect against experimental pneumococcal infection in
      mice, is capable of increasing the threshold value of the type homologous
      antipneumococcus serum at least fifty times. 2. This effect is proportionately
      many times greater than a simple summation of the protective effects of these two
      bodies. 3. No such effect is obtained when the antiserum used is one produced
      against a strain of pneumococcus from a group other than that to which the
      infecting pneumococcus belongs.

PMID- 19867925
TI  - THE MECHANISM OF ANAPHYLACTIC SHOCK : STUDIES ON FERMENT ACTION. XXIII.
AB  - 1. The serum ferments are practically unaltered by a primary injection of foreign
      protein. 2. During the course of sensitization the injection of the antigen is
      followed by the mobilization of a non-specific protease which increases in
      rapidity and intensity as the maximum period of sensitization is reached. 3.
      Acute shock is accompanied by: (a) The instantaneous mobilization of a large
      amount of non-specific protease; (b) a decrease in antiferment; (c) an increase
      in non-coagulable nitrogen of the serum; (d) an increase in amino-acids; (e) a
      primary decrease in serum proteoses. 4. Later there is a progressive increase in
      the non-coagulable nitrogen, in proteoses, and in serum lipase. 5. The acute
      intoxication is brought about by the cleavage of serum proteins (and proteoses)
      through the peptone stage by a non-specific protease. 6. The specific elements
      lie in the rapid, mobilization of this ferment and the colloidal serum changes
      which bring about the change in antiferment titer.

PMID- 19867926
TI  - A CONTRIBUTION TO THE BIOLOGY OF PERIPHERAL NERVES IN TRANSPLANTATION.
AB  - In autoplastic transplanted nerves a degenerative process occurs which resembles
      the ordinary Wallerian degeneration, but appears a little more slowly than the
      latter. The cells of Schwann are in a condition of survival and are capable of
      multiplication after the transplantation. In homoplastic transplanted nerves I
      have found a degenerative process resembling a Wallerian degeneration, somewhat
      delayed. The cells of Schwann multiply, and for some time at least are in a
      condition of survival. After twelve to fourteen days an abundant and increasing
      immigration of lymphocytes is observed, and from the eighteenth day the cells of
      Schwann develop a necrobiotic appearance. In heteroplastic transplanted nerves
      numerous myelin ovoids are formed during the first four to five days, but there
      is no proliferation of the cells of Schwann, and no Wallerian degeneration is
      seen. The graft becomes necrotic within about two weeks. The formation of ovoids
      that occurs during the first four to five days after the performance of the
      heteroplastic transplantation does not reveal the condition of the life of the
      graft. This formation of myelin ovoids is found in the nerve fibers when they
      have been kept in an incubator for twenty-four hours in Ringer solution
      (Nageotte(12)) or in homologous or heterologous serum, but it is not found in the
      fibers after their incubation in isotonic salt solution (Nageotte), the presence
      of calcium being necessary for the occurrence of ovoid formation. Heteroplastic
      transplanted nerves become necrotic. They are unsuitable for bridges in cases of
      nerve defects, and my results explain the failure of the attempts at
      heteroplastic transplantation of nerves in human beings. If we wish to bridge a
      nerve defect by implantation we must use autoplastic or homoplastic grafts. The
      occurrence of a Wallerian degeneration in these grafts during the first two to
      three weeks after the transplantation should make bridging a promising operation;
      for in this period the grafts resemble the peripheral part of a divided nerve and
      must be assumed to be capable of regeneration, and thus are very different from
      dead material. I have studied the process of regeneration, and shall communicate
      in a future article my results of bridging defects, which are encouraging as far
      as the function is concerned. My results with homoplastic transplantation of
      nerves have a bearing on the homoplastic transplantation of limbs, which has been
      successfully performed in dogs by Carrel. None of his dogs lived long enough to
      show any function of the transplanted leg. The practical value of this operation
      is dependent, of course, upon the return of function, and especially on the
      regeneration of the nerves in the transplanted leg. The results with homoplastic
      transplantation of nerves seem to indicate the possibility of a regeneration of
      the nerves in a homoplastic transplanted leg.

PMID- 19867927
TI  - THE DIAGNOSTIC VALUE OF THE PLACENTAL BLOOD FILM IN AESTIVO-AUTUMNAL MALARIA.
AB  - 1. The placental blood film examination is worthy of routine application wherever
      aestivo-autumnal malaria is endemic. This type of malaria when associated with
      labor and the early days of the puerperium can be more easily and certainly
      diagnosed by the use of this film and a polychrome stain than by employing the
      usual films made from the mother's peripheral blood at the time of labor. The
      placental film in such an infection offers an abundance of adult parasites and
      far more evidence of the presence of pigment, while the peripheral blood film
      frequently offers but a scant number of the small ring or discoid forms of a
      parasite. The examination of the present series revealed positive placental films
      in nineteen cases, while but eight of these same cases were positive in the
      peripheral blood film examination. On the other hand, no peripheral blood films
      were found positive in which the associated placental films did not reveal a far
      more abundant evidence of the infection. 2. The early days of the puerperium can
      by this method be protected many times from a malarial outburst, and, as a rule,
      puerperal sepsis can be differentiated. 3. The intricate vascular architecture of
      the mature placenta rivals that of the spleen, liver, and bone marrow as a harbor
      for adult malarial parasites of this type and as a storage for pigment. 4. The
      localization of parasites in the placenta is unique. Here is the one vascular
      system which particularly favors the development of the parasites but which at
      the same time is so situated that it may be spontaneously discarded by the body
      at the climax of the attack. By this simple act late in pregnancy the prognosis
      for both mother and child may be improved. 5. The pregnant state encourages
      attacks of malaria by lowering bodily resistance and by furnishing an additional
      harbor for the development of parasites. A tenable theory in regard to most
      attacks of this nature, occurring in cases under professional care, would appear
      to be the development of latent malaria (malarial carriers) into acute attacks
      toward the close of the pregnant state. The women who expose themselves (as the
      negroes in this series) offer favorable conditions to the introduction of a
      primary infection. Malaria frequently interrupts the late stages of pregnancy and
      sometimes causes the death of the mother and the fetus, more often the latter.
      The records at Ancon indicate that it more frequently exerts a harmful influence
      than other types of infectious diseases in this locality. 6. Most of the children
      in this series that were delivered while malaria was present in the mother, were
      of a race that seems to possess a relative immunity to the ravages of malaria.
      This may account for the fact that the negro fetus more nearly approximates the
      full term of development when associated with this disease and is comparatively
      subjected to a less number of the accidents of pregnancy. Many of them revealed
      evidence of prematurity and were jaundiced, but, as a rule, they developed
      rapidly. The commonest mishap is miscarriage late in pregnancy. Occasional still
      births occur and sometimes there is a fatal issue to both the mother and child.
      7. Cases diagnosed as congenital malaria probably indicate that some accident
      occurred to the placenta, because it practically never happens that fetal blood
      is positive at the time of birth, regardless of the degree of infection in the
      mother. Many of the cases now reported in the literature as congenital malaria
      suggest immediate postnatal infection as their history, as our pathological and
      clinical records testify. 8. The size of the intervillous spaces of the placenta
      and their adaptability in the localization of parasites seem to disprove to a
      certain extent the old idea that the localization depends on the smallness of the
      capillary caliber. If this were the case the brain should be more often the seat
      of an extensive localization than the spleen, bone marrow, and placenta, yet our
      anatomical records will not support that theory. A sluggish blood sinus with a
      large endothelial surface, a higher internal body temperature, and red blood
      cells burdened with parasites of a certain age beyond the ring form seem to be
      important factors in the localization and development of the aestivo-autumnal
      parasite. 9. The racial disparity of malarial infections shown in this series is
      believed to be due to local conditions and a wrong impression is apt to be given
      by our statistics in regard to the relative immunity of the negro race. The white
      women on the Canal Zone avail themselves of all the opportunities the sanitary
      system affords; they live well and place the entire course of their pregnant
      state under competent professional care, while the negro woman is indifferent to
      her pregnant state, works as a domestic servant, and lives in the cheapest
      unprotected quarters that can be rented in the suburban divisions of Panama City
      where the malarial rate is highest and the sanitary control is difficult. It
      should be noted that these negro women can carry an infection with little
      manifestation of its presence that would produce serious results in the white
      women brought from the temperate zone regions of Europe and the United States.

PMID- 19867928
TI  - AN IMMUNOLOGICAL STUDY OF BACILLUS INFLUENZAE.
AB  - Influenza bacilli isolated from various pathological processes in man differ
      widely in pathogenic power for animals, especially rabbits. While the cultures
      derived from the leptomeninges and blood, and rarely from the pneumonic lung are
      pathogenic, those generally derived from the respiratory tract exhibit little or
      no virulence for rabbits. The two types of cultures as indicated by virulence for
      animals do not differ in kind, but only in degree, in relation to the serological
      tests of agglutination, complement deviation, and opsonification. The two types
      of cultures do, however, differ with respect to their ability to undergo
      autolysis. While the virulent cultures autolyze almost completely, yielding a
      turbid supernatant fluid and little sediment, the non-virulent cultures give rise
      to an abundant sediment and a clear supernatant fluid. The non-virulent cultures
      incite far less antibody production in rabbits. Hence, rabbits inoculated with
      non-virulent strains yield sera possessing low antibody content. Conversely,
      rabbits inoculated with virulent strains yield sera possessing a higher content
      of antibody. In keeping with and possibly because of the low antibody content of
      the sera of rabbits inoculated with the non-pathogenic strains, the rabbits so
      treated are not, as a rule, protected against subsequent inoculation with
      virulent strains. . Influenza bacilli therefore vary in pathogenic effect both
      for man and animals, but they are not distinguishable by means of serological
      reactions into different types. Apparently all influenza bacilli belong to one
      class or race irrespective of origin or virulence.

PMID- 19867929
TI  - THE MECHANISM OF THE CURATIVE ACTION OF ANTIPNEUMOCOCCUS SERUM.
AB  - An active antipneumococcus serum causes agglutination of pneumococci in vitro and
      in vivo. The antiserum acts in far greater dilution in causing agglutination as
      determined by the microscopic than by the macroscopic test. The antiserum when
      injected into the circulation of rabbits suffering from pneumococcus bacteremia
      causes a rapid disappearance of the diplococci from the blood. This disappearance
      is brought about by instantaneous clumping of the diplococci in vivo and the
      removal of the clumps by the liver, spleen, lungs, and possibly other organs.

PMID- 19867930
TI  - A METHOD OF SERUM TREATMENT OF PNEUMOCOCCIC SEPTICEMIA IN RABBITS.
AB  - The treatment of pneumococcic septicemia in the rabbits by large doses of immune
      serum is detrimental, since the serum causes the formation of large clumps of
      bacteria in the blood which are taken out chiefly by the vessels of the lungs in
      which they accumulate and impede the circulation. The large doses of serum are
      also detrimental when they follow upon small ones through which the small clumps
      formed are deposited in the spleen, liver, and other organs. In this instance,
      the large amount of serum leads to the destruction of the pneumococci under
      conditions which promote an intoxication. The precise mechanism of this action is
      not known. The treatment of pneumococcic septicemia in rabbits by small repeated
      doses of immune serum can be successfully carried out. The number of pneumococci
      capable of being brought to destruction through phagocytosis in the organs in
      this way is very great. Not all the rabbits treated with small repeated doses of
      the serum survive. Those that succumb do so not to a general infection but to a
      pneumococcus meningitis. The explanation of this phenomenon is simple. When the
      number of pneumococci originally inoculated is very great a small number
      penetrate into the subdural space. Those in this space do not come under the
      influence of the serum, hence they are not agglutinated and prepared for
      phagocytosis, whence they multiply and set up a fatal meningitis. The activity of
      the immune serum administered in this way against virulent pneumococci is so
      great that a revision of our notions in the limit of powers of the anti
      infectious sera seems necessary. It is patent that the problem is not simply a
      relation between quantity of immune bodies and number of bacteria. It is more
      complex than that conception indicates. The factor of the leucocytes and the
      degree of their possible activities under the conditions of the experiment come
      into play. Hereafter, in defining the mode and power of action of anti-infectious
      sera the condition of cooperation of the body-forces will have to be more
      strictly considered.

PMID- 19867931
TI  - THE FATE OF TYPHOID BACILLI WHEN INJECTED INTRAVENOUSLY INTO NORMAL RABBITS.
AB  - Typhoid bacilli are agglutinated promptly in the circulating blood of normal
      rabbits and quickly removed from the blood stream. The clumped bacilli accumulate
      in the organs and are taken up by assembled polymorphonuclear leucocytes in the
      liver, spleen, and possibly other organs. The phagocyted clumps of bacilli are
      digested and destroyed by the phagocytes. Hence, destruction of typhoid bacilli
      intra vitam is brought about by an entirely different process than is the
      destruction by serum and whole blood in vitro. While the latter is caused by
      bacteriolysis, the former results from agglutination and intraphagocytic
      digestion. Lysis by fresh blood serum is not appreciably affected by spleen or
      kidney pulp, but it is inhibited by liver pulp. The action of the liver is
      referable to its biliary constituents, which exert anticomplementary action.
      Probably in certain examples of typhoid fever in man the typhoid bacilli in the
      circulating blood being inagglutinable cannot be removed by the organs and hence
      are not phagocyted and destroyed. The observed disparity between the ready
      destruction of typhoid bacilli by serum and shed blood and the resistance
      sometimes offered by the bacilli in the infected body is explained by the
      essential differences in the destructive processes in operation within and
      without the body.

PMID- 19867932
TI  - THE AGGLUTINATION OF BACTERIA IN VIVO.
AB  - 1. Small quantities of antiserum bring about instantaneous agglutination of
      pneumococci in the circulation of the rabbit; the reaction is specific and occurs
      in every case in which sufficient serum is given to influence the course of the
      septicemia or to prolong the life of the animal. 2. The agglutinating titer of
      antipneurnococcus serum can be made considerably higher by adding only a small
      quantity of culture to the tests, thus making the test a finer differential. 3.
      Typhoid bacilli agglutinate spontaneously in the circulation of the normal
      rabbit; the reaction is positive in vivo even in cases in which undiluted serum
      gives a negative result in vitro; heating the bacilli to 80 degrees C. for thirty
      minutes renders them more agglutinable in vivo. 4. Dysentery bacilli of the Shiga
      type do not agglutinate in the blood stream of the normal rabbit, but a small
      quantity of antiserum injected into the circulation causes immediate
      agglutination; while all strains of the Flexner group undergo spontaneous
      agglutination. 5. Non-virulent influenza bacilli agglutinate spontaneously in the
      circulation of the normal rabbit; virulent strains remain in the blood unclumped.
      6. In all instances so far investigated of both passive and natural immunity,
      agglutination of the bacteria within the blood of the infected animal was
      followed by a rapid removal of the bacteria from the circulation, and by
      phagocytosis and destruction of the agglutinated bacteria in the capillary
      systems of the viscera; while those bacteria which are not agglutinated remain in
      the circulation and produce a progressive septicemia. 7. Hence the agglutinins
      seem to play the decisive part in at least certain instances of bacterial
      infections.

PMID- 19867933
TI  - FATTY DEGENERATION OF THE CEREBRAL CORTEX IN THE PSYCHOSES, WITH SPECIAL
      REFERENCE TO DEMENTIA PRAECOX.
AB  - From the data provided by our investigations we may conclude that in all
      pathologic processes of the cortex which end in dementia and death, the fatty
      degeneration of the elements of the cortex plays a not unimportant part. The
      characteristic change for most of the psychoses is found in a great increase in
      amount of fatty deposits when compared to normal individuals of the same age. In
      some processes such as senile dementia and dementia praecox the fatty substance
      appears to fill completely the cell body, and these cells have apparently lost
      all their functioning power. It is not common to find the fatty deposits in the
      processes of the ganglion cells except in dementia praecox, and to a limited
      extent in senile dementia. In other cases the pathological variety of the fatty
      deposits in the ganglion cells is seen to be diffused over the whole ganglion
      cell. We were able especially to observe this in infectious psychoses, in general
      paralysis, and in epilepsy. The so called central neuritis assumes a peculiar
      attitude in that it plainly leads swiftly to an acute fatty degeneration of the
      ganglion cells, in which there exists an inclination of the fatty granules to
      flow together into large masses. Frequently the fatty degeneration of the
      ganglion cells appears to be connected with the sclerosis of the cells,
      especially when it is a matter of slowly progressing alterations of degeneration.
      The behavior of the glia is not wholly uniform in the various disease processes.
      In chronic disease processes we often find that the extent of the fatty
      accumulations in the ganglion cells does not correspond to an equal increase in
      the glia cells, while the otherwise acutely degenerative alteration in the nuclei
      of the glia is noticeable. In acute processes we see regularly an equal
      accumulation of the fat in both species of cell. The conditions of the cells in
      the vascular wall are wholly similar to those of the glia cells. We must
      therefore assume that in chronic diseases the fatty substance has been carried
      out of the glia and the vascular walls while it has been retained longer in the
      ganglion cells. Among all the disease processes amaurotic idiocy assumes a
      peculiar position. We have observed that in addition to the fatty materials of
      the scarlet fat stain, still other fatty materials, lipoid in character, have
      made their appearance. While the study of the fatty deposit in the cerebral
      cortex offers some points for a differential diagnosis, yet it is not adopted in
      all cases, since the distinction in individual disease processes is not always
      characteristic. From the preceding examination, however, in many cases there
      result important findings which briefly we summarize as follows: 1. In all
      degenerative alterations in the cerebral cortex the mass of the lipoid materials
      in the ganglion cells in comparison with that in healthy individuals of equal age
      is found to be considerably augmented. In the alteration of the lipoid materials
      in the ganglion cells two types in general may be distinguished: (a) An
      augmentation of the lipoid materials in the ganglion cells, in places where
      normally a small amount of fat is found, (b) An augmentation of the lipoid
      materials over the entire cell. 2. The first type we find also characteristic in
      senile dementia. The second type occurs in acute infectious psychoses, general
      paralysis, and well advanced epilepsy. 3. While the advanced lipoid degeneration
      of the ganglion cells in senile dementia has already been described in many ways,
      it has appeared from our investigations that also in the young chronic cases of
      dementia praecox far-reaching fatty degeneration of the ganglion cells,
      especially in the second and third cortical strata, likewise occurs. These
      findings should constitute an important contribution to the pathological anatomy
      of dementia praecox. 4. The so called central neuritis represents a peculiar
      disease process according to the appearance of the fatty degeneration, since this
      fatty degeneration reaches a very advanced degree, and also in so far as it
      deviates from other disease processes in that here there comes out very
      distinctly in the picture an inclination of the fatty granules to flow together.
      5. Amaurotic idiocy also represents a particular disease process in respect to
      the lipoid degeneration, since here in addition to otherwise distributed scarlet
      stain lipoid materials, still other specific lipoid materials make their
      appearance.

PMID- 19867934
TI  - CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC : I. TYPES OF THE ARSENIC
      KIDNEY.
AB  - 1. All arsenical compounds do not produce the same type of renal injury. 2. In
      general, there are two broad groups of kidneys produced, the red and the pale,
      with a variety of subdivisions of each group depending upon modifications in the
      chemical constitution of the compound, dosage, and length of survival of the
      animal.

PMID- 19867935
TI  - CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC : II. HISTOLOGICAL CHANGES IN
      ARSENIC KIDNEYS.
AB  - 1. We have shown that the type of renal lesion produced by compounds of arsenic
      varies widely: while some arsenicals produce changes in which vascular injury
      predominates, others produce an equally dominant tubular injury. 2. In either of
      these groups the character and degree of the vascular or tubular injury produced
      by different compounds shows further variation, such that the lesions of
      different arsenicals of the same group are not identical. Each compound of
      arsenic that we have tested, therefore, produces a lesion-complex in the kidney
      that is relatively characteristic for that compound. 3. The mode and character of
      the action of arsenicals are dependent upon the chemical constitution of the
      compound.

PMID- 19867936
TI  - CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC : III. ON THE PATHOLOGICAL
      ACTION OF ARSENICALS ON THE ADRENALS.
AB  - 1. Toxic doses of all arsenicals of which we have any knowledge produce definite
      pathological changes in the adrenals of guinea pigs. These changes include
      congestion, hemorrhage, disturbances in the lipoid content, cellular
      degenerations and necroses, and reduction in the chromaffin content. 2. The
      character and severity of the injury produced by different arsenicals varies with
      the chemical constitution of the compounds. 3. From these facts, we believe that
      adrenal injury is an important factor in arsenical intoxication and suggest that
      therapeutic doses of some arsenicals may produce adrenal stimulation.

PMID- 19867937
TI  - A NOTE ON THE IMMEDIATE EFFECTS OF REDUCTION OF KIDNEY SUBSTANCES.

PMID- 19867938
TI  - A FURTHER STUDY OF THE BACTERICIDAL ACTION OF ETHYLHYDROCUPREIN ON PNEUMOCOCCI.
AB  - 1. The serum of rabbits which have been previously treated with a single dose of
      ethylhydrocuprein (optochin) exerts a bactericidal action on, and, later,
      inhibits the growth of pneumococci in the test-tube. 2. These actions are most
      evident in the serum of rabbits when the base (optochin base) is given in oil
      subcutaneously; somewhat less when the hydrochloride of the drug is given in
      water subcutaneously; slight when the base is given in oil intramuscularly; and
      least evident, or absent, when the hydrochloride in water is introduced directly
      into the stomach. To get these effects by the intravenous route, toxic doses must
      be given, and, even with toxic non-fatal doses, the effects do not last long. 3.
      In the case of the base given in oil subcutaneously to rabbits in a dosage of 0.1
      gram per kilo of body weight, the bactericidal action of the serum is at its
      maximum about one hour after administration, and it passes into an inhibitory
      effect about four hours after the drug has been given. 4. In man the same
      inhibitory and bactericidal actions of the serum are present when a single dose
      of 0.5 gram of the hydrochloride of the drug is given by the mouth or
      subcutaneously, but the bactericidal action is not so marked as in rabbits. 5.
      When the optochin concentration in the serum has, apparently,. diminished to a
      certain point in relation to the number of pneumococci present, the pneumococci
      which have survived the bactericidal action for a few hours acquire the power of
      growing freely.

PMID- 19867939
TI  - THE SERUM FERMENTS AND ANTIFERMENT DURING PNEUMONIA : STUDIES ON FERMENT ACTION.
      XXIV.
AB  - 1. The crisis in pneumonia is usually accompanied by (a) decrease in the serum
      antiferment; (b) the mobilization of a non-specific protease in the serum; (c) an
      increase in serum lipase; (d) a decrease in the non-coagulable nitrogen, and of
      the proteoses in the serum. 2. The crisis is associated with the beginning of an
      active autolysis, the latter depending on an altered relation between the ferment
      antiferment balance. 3. The fibrin and leucocytic debris must be considered as
      one of the potential sources of toxic substances. With rapid autolysis
      proceeding, only non-toxic materials are absorbed.

PMID- 19867940
TI  - SERUM CHANGES FOLLOWING KAOLIN INJECTIONS : STUDIES ON FERMENT ACTION. XXV.
AB  - 1. The intoxication produced by the intravenous injection of inert substances
      such as kaolin is due to protein split products derived from the serum proteins.
      2. The kaolin acts as an adsorbing medium for the serum antiferment, bringing
      about an alteration in the ferment-antiferment balance. 3. The intoxication is
      accompanied by an increase in serum protease, and of proteoses. 4. The serum
      lipase, the amino-acids, and the total non-coagulable nitrogen show relatively
      little change. 5. The antiferment shows an initial increase, followed by a loss.

PMID- 19867941
TI  - THE EFFECT OF PROTEIN SPLIT PRODUCTS ON THE SERUM FERMENTS AND ANTIFERMENT :
      STUDIES ON FERMENT ACTION. XXVI.
AB  - 1. In dogs the toxic effect of primary proteoses is usually associated with the
      following serum changes: (a) an increase in serum antiferment, with a following
      fall in titer; (b) some increase in serum protease; (c) an increase in serum
      lipase; (d) a decrease in serum proteoses and amino nitrogen. 2. Secondary
      proteoses produce (a) less marked changes in the antiferment titer; (b) a marked
      increase in serum protease; (c) an increase in serum proteoses; (d) only a slight
      change in serum lipase; (e) a primary decrease in amino nitrogen. 3. The peptone
      which we have used (prepared from dog muscle) caused (a) a change in antiferment
      titer similar to that produced by the primary proteoses; (b) a marked increase in
      serum protease; (c) only a slight increase in serum lipase; (d) a primary
      decrease in proteoses, followed by an increase later; (e) an increase in amino
      acids. 4. A very small dose of peptone resulted in a decrease in antiferment
      titer, together with a primary decrease in serum protease. 5. The peptone
      preparation was non-toxic when introduced into the stomach or rectum, while the
      intestinal injection was followed by an immediate intoxication.

PMID- 19867942
TI  - THE EFFECT OF KILLED BACTERIA ON THE SERUM FERMENTS AND ANTIFERMENT : STUDIES ON
      FERMENT ACTION. XXVII.
AB  - 1. The intravenous injection of killed organisms is followed by the mobilization
      of a non-specific protease and lipase; the rapidity and extent of this reaction
      depend upon the toxicity of the organism and on the resistance of the organism to
      proteolysis. 2. The temperature and leucocytic curve bear no relation to the
      ferment changes. 3. The serum antiferment is usually increased after the
      injection. 4. Of the organisms studied, the typhoid bacilli produced the most
      marked ferment changes, and the tubercle bacilli the least. 5. The toxicity of
      the dried organisms cannot depend wholly upon proteolysis in vivo, but must
      depend in part on the preformed toxic substances liberated on lysis. 6. Serum
      protease should not be considered as the sole exciter of intoxication through the
      production of protein split products; it seems possible that its function may in
      part be one of detoxication.

PMID- 19867943
TI  - A STUDY OF THE CULTIVATION OF THE TUBERCLE BACILLUS DIRECTLY FROM THE SPUTUM BY
      THE METHOD OF PETROFF.
AB  - 1. Probably in the majority of cases it is possible, with scrupulous technique,
      to isolate the tubercle bacillus from contaminated material such as the sputum,
      by the method outlined by Petroff. 2. It is necessary to use several tubes. 3.
      Neutralization, drying, temperature of the incubator, and contamination after the
      growth has started are important points to be noted in the process. 4. The
      colonies start as pin points, becoming larger and confluent, but still preserving
      individual groups of a dry appearance which simulate the medium closely in color.
      5. The bacillus of tuberculosis in young culture is tinctorially acid-fast and of
      a polymorphous morphology.

PMID- 19867944
TI  - EXPERIMENTAL ARTHRITIS IN THE RABBIT. A CONTRIBUTION TO THE PATHOGENY OF
      ARTHRITIS IN RHEUMATIC FEVER.
AB  - By a process of sensitization described it was found possible to cause arthritis
      in rabbits constantly after one intravenous injection of the streptococcus. This
      reaction is specific. By intravenous inoculation, without previous sensitization,
      of the streptococcus used in these experiments it was possible to cause arthritis
      in rabbits only after three or more injections. An analogy is suggested between
      the arthritis induced by sensitization and the relapses in human rheumatic fever.
      A further analogy is suggested between the development in rabbits of arthritis
      after repeated intravenous injections and the development of the primary lesion
      in human rheumatic fever.

PMID- 19867945
TI  - THE ACTION OF THE LETHAL DOSE OF STROPHANTHIN IN NORMAL ANIMALS AND IN ANIMALS
      INFECTED WITH PNEUMONIA.
AB  - The results of these experiments permit a comparison of the action of
      strophanthin in the normal and the infected animals. In cats the percentage of
      deaths following the injection of 0.1 mg. of strophanthin per kilo of body weight
      was the same in normal and in pneumonic cats. The number of recoveries in this
      series was larger than was expected. This result was due to the fact that the
      dose injected was not the lethal dose, but the average lethal dose (0.1 mg.)
      determined by Hatcher and Brody (7) and by Eggleston (8). The doses which the
      latter actually injected ranged from 0.085 rng. to 0.16 mg.; from these the
      average minimal lethal dose was calculated. In adopting the average dose as the
      standard one to inject, those of our cats that required more than 0.1 mg.
      naturally survived. The death rate was therefore low. The plan employed in dogs
      differed from that used in cats. A lethal dose was injected in each dog. Death
      occurred when an average of 0.12 mg. of strophanthin per kilo of body weight was
      injected. The same dose was required in normal and pneumonic dogs. The effect of
      strophanthin in both groups of infected and non-infected cats and dogs is,
      therefore, identical. Whether the uniformity of strophanthin action in the two
      experimental groups may serve as the basis for assuming a like uniformity of
      action in normal individuals and in pneumonia patients is a subject which
      requires further analysis. The difficulty in transferring the experimental
      results to patients lies in the question of whether the type of pneumonia
      produced in animals is the same as that found in man. Clinically, the two
      diseases present both resemblances and differences. The animals become definitely
      ill and show the symptoms already described. The illness, however, is of short
      duration and apparently reaches its height in the majority of animals in twenty
      four to seventy-two hours. Before the expiration of this time, the temperature
      frequently returns to normal. Many of the infected animals, when they survive,
      recover in three to five days. The mortality in dogs infected with pneumococci is
      given by Lamar and Meltzer as 16 per cent. In the present series of twelve
      infected cats, the mortality was also 16 per cent. These findings differ from
      human pneumonia in the following particulars: The infection is not so severe; the
      temperature, though elevated at first, soon falls; the duration of the disease is
      short; and convalescence is rapid. The mortality is slightly lower. Musser and
      Norris (12) give the human mortality at 21.06 per cent. Pathologically the two
      diseases also show differences. The gross appearance of the lungs is not
      dissimilar, but in the animals the consolidated portions are somewhat dry and
      they fail to show a stage of gray hepatization (5). The amount of fibrin present
      is small. There is comparatively slight congestion of the alveolar walls and of
      the walls of the bronchi. The relation of experimental pneumonias to the human
      disease has been discussed by a number of investigators. Almost all believe that
      the two types are similar, if not identical. Among the first to express this
      opinion was Sternberg (13) ; and later Gamaleia (14), Prudden and Northrup (15),
      Kinyoun and Rosenau (16), Wadsworth (17), Lamar and Meltzer (5), Wollstein and
      Meltzer (9) coincided with his view. Lamar and Meltzer, especially, have insisted
      on the identity of the two processes. On the other hand, Welch (18) in his study
      of experimental pneumonia, says: "Many inoculations of cultures of virulent
      pneumococci into the trachea and lungs of dogs have been made in my laboratory by
      Dr. Canfield and myself, but in no instance were we able to produce an
      inflammation of the lungs which we were willing to identify with acute lobar
      pneumonia as found in human beings." But he adds that, in the majority of
      experiments, there was no demonstrable consolidation and that pleurisy and more
      or less extensive areas of pneumonia were produced only in a few animals. The
      inference consequently cannot be drawn that an effect obtained with strophanthin
      in the experimental disease may be anticipated in man. The striking similarity in
      action in infected and uninfected animals renders it likely, however, that the
      usual action of the drug in man may be expected in the presence of pneumonia. We
      have accumulated evidence, to be published later, which shows that this action
      actually takes place in the human disease. As far as evidence obtained
      electrocardiographically is concerned, our experiments show that strophanthin
      causes the same electrical changes in the heart when the animals are infected as
      it does under normal conditions.

PMID- 19867946
TI  - FURTHER INVESTIGATIONS ON THE ORIGIN OF TUMORS IN MICE : I. TUMOR INCIDENCE AND
      TUMOR AGE IN VARIOUS STRAINS OF MICE.
AB  - 1. It is possible to split a strain of mice into certain substrains in which the
      tumor incidence is in some way linked to the color of the mice. Thus we could
      split off from the English strain, which as a whole and in various substrains
      with mixed colors (English A and Sable) has a high tumor rate, substrains with
      light tan color and pink eyes (IOI and Tan) which have a high tumor rate like the
      large majority of the English mice, and two other apparently recessive strains
      breeding true, which have a very low tumor incidence (Silver and Silver Fawn).
      Therefore, certain combinations of factors which determine certain colors of mice
      determine at the same time the tumor incidence of these strains or substrains. In
      the majority of cases isolated families bred through several generations
      separately from the majority of the other substrains give approximately the same
      tumor rates as the others; in some cases, however, it may perhaps be possible to
      separate from the main strain a family with a different rate. 2. The tumor
      incidence and the tumor age found in the earlier periods of our work are
      approximately the same as in the more recent period. On the whole, the results
      obtained in successive generations of the same strain also agree well with each
      other; the results are fairly constant; the deviations which occur are in most
      cases due to the small number of animals observed in the certain generations.
      Discarding all the mice dying in the first or in the first and second periods of
      life usually does not alter essentially the tumor ratio of a certain strain. 3. A
      certain relationship exists between tumor frequency and tumor age. On the whole,
      the more frequent the tumors, the earlier they appear in the various strains.
      This parallelism between tumor frequency and tumor age is, however, not complete.
      The tumor age seems to be as characteristic for a certain strain as the tumor
      rate. Certain substrains which differ in tumor frequency may show approximately
      the same tumor age. Strains with similar tumor frequency may show a different
      tumor age. We may therefore conclude that in all probability tumor rate and tumor
      age represent distinct unit factors, which are frequently, but not in all cases,
      linked in some manner to each other. 4. The age at which the maximum of tumors
      appears varies in different strains. The maximum may fall into the second or
      third period of life. On the whole, the maximum is reached at an earlier period
      of life in those strains which have a high tumor rate. But here also
      peculiarities exist in different strains.

PMID- 19867947
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : XII. THE IMPORTANCE IN THE PRODUCTION OF HEMOLYTIC JAUNDICE OF THE
      PATH OF HEMOGLOBIN TO THE LIVER.
AB  - These experiments indicate, therefore, that when hemoglobin is set free in the
      portal circulation a larger amount is held by the liver and converted rapidly
      into bile pigment than is the case when it is set free in the general
      circulation, and that, under the former condition, over-loading of the liver with
      bile pigment more readily occurs and jaundice is more apt to develop. This
      mechanical influence must, therefore, be a factor in the lessened tendency after
      splenctomy to the jaundice which follows blood destruction due to hemolytic
      agents, for whether the spleen be an active factor in destroying the erythrocytes
      or whether it plays merely a passive part as a place for the deposition of the
      disintegrating cells, there can be no question that in this organ, when it is
      present, a large number of cells undergo their final disintegration after the
      action of hemolytic poisons, and that the hemoglobin there liberated passes by
      the portal system directly to the liver. When the spleen is removed, this
      disintegration occurs in other organs, notably in the lymph nodes and bone
      marrow, and the hemoglobin from these organs passes not into the portal but into
      the general circulation, from which it reaches the liver more gradually and in a
      more dilute form.

PMID- 19867948
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : XIII. THE INFLUENCE OF DIET UPON THE ANEMIA FOLLOWING SPLENECTOMY.
AB  - The anemia which develops after splenectomy is most marked in animals on a mixed
      table scrap diet of meat, bread, cereals, and vegetables, which is essentially a
      cooked diet. Control studies in which a unilateral nephrectomy precedes
      splenectomy demonstrate that the anemia is not due to operation, hemorrhage, or
      accidents of convalescence but develops only in the absence of the spleen. The
      results of studies of the influence of food containing a large amount of iron in
      presumably easily utilizable form, as in raw beef spleen, do not support the view
      that the anemia is due to lack of iron in the food. Observation on the influence
      of a diet of raw meat as contrasted with cooked meat shows a more severe anemia
      in animals on the cooked diet and suggests the possibility that heat alters some
      substance which, in the absence of the spleen, the body cannot utilize. A final
      conclusion in regard to this point must, however, await the results of more
      detailed studies now in progress.

PMID- 19867949
TI  - STUDIES ON THE CIRCULATION IN MAN : XVI. A STUDY OF THE DEVELOPMENT OF THE
      COLLATERAL CIRCULATION IN THE RIGHT HAND AFTER LIGATION OF THE INNOMINATE ARTERY
      FOR SUBCLAVIAN ANEURYSM.
AB  - The development of the collateral circulation after ligation of the innominate
      and right common carotid arteries for subclavian aneurysm was studied in two
      cases by measuring the rate of blood flow in the hand's from time to time. In a
      woman, sixty-eight years old, the flow in the right hand three weeks after the
      operation was two-sevenths of that in the left. Nineteen weeks after the
      operation the flow in the right hand was more than three-fourths of that in the
      left, although no pulse returned until long afterwards. In a man, twenty-five
      years old, the flow in the right hand eleven days after the operation was between
      one-fourth and one-fifth of that in the left. Seventeen days after the operation
      the flow in the right hand was nearly one-third of the flow in the left. Twenty
      four days after the operation the flow in the right hand had increased to more
      than one-half of the left hand flow. Thirty-one days after the operation the flow
      in the right hand was three-fifths of that in the left, without return, as yet,
      of any pulsation. Before the operation the flow in the right hand was markedly
      greater than in the left, notwithstanding the small size of the right radial
      pulse as compared with the left. The explanation of this fact is discussed.

PMID- 19867950
TI  - THE ACCELERATION OF ESTERASE ACTION : STUDIES ON FERMENT ACTION. XXVIII.
AB  - 1. Potassium citrate, potassium oxalate, and calcium lactate accelerate the
      action of tissue and serum esterases. 2. Intravenous and intraperitoneal
      injections of large amounts of sodium citrate do not cause a definite increase in
      the activity of the serum esterase.

PMID- 19867951
TI  - THE RELATION OF SERUM ESTERASE TO LIVER DESTRUCTION : STUDIES ON FERMENT ACTION.
      XXIX.
AB  - 1. Liver tissue showing fatty degeneration obtained from animals poisoned with
      phosphorus or chloroform contains a decreased amount of esterase. 2. The serum of
      animals poisoned with phosphorus or chloroform has a high esterase activity. 3.
      The increased amount of esterase in the serum is not derived from the
      disintegrating liver cells as the esterase in the blood of the hepatic vein is
      less than that found elsewhere.

PMID- 19867952
TI  - FURTHER INVESTIGATIONS ON THE ORIGIN OF TUMORS IN MICE : II. TUMOR INCIDENCE AND
      TUMOR AGE IN HYBRIDS.
AB  - 1. In crossing strains known to diner in their tumor rates, the hybrids show in a
      considerable number of cases a tumor rate corresponding to the parent with a high
      tumor incidence; in some cases the offspring have the tumor rate of the parent
      with the low tumor incidence; in certain cases the tumor rate of the offspring is
      intermediate between those of the parents. That these results are not accidental
      follows from the fact that we could show in some cases that two sisters crossed
      with the same strains or with the same male give similar offspring, and in other
      cases we could show that the same individual crossed successively with two
      strains that behave similarly produces hybrids with a similar tumor incidence. 2.
      There exists some evidence for the conclusion that different strains in being
      crossed with other strains differ in their power to impress their tumor rate upon
      the crosses. Thus the English strain and the I and II daughters of No. 10 have
      the tendency to transmit to the offspring a high tumor rate, while Cream, Silver,
      and some European other than 151 have a tendency to transmit a low tumor rate.
      While crosses of these daughters of No. 10 with European 151 or with No. 8(1/2)
      show the high tumor rate of the mothers, the crosses of one of the same females
      with Cream or Silver show an intermediate tumor rate. 3. We find further evidence
      for our conclusion previously stated that age class, of the tumors and tumor rate
      are not dependent on the same factor. The age class enters into the crosses as a
      factor independent of the tumor rate. Thus we find in the crosses between the
      first daughter of No. 10 and Cream, and in the crosses between the same female
      and English Silver a similar tumor rate, but the age classes differ in conformity
      with the difference in the age classes of the parents. We find, furthermore, that
      while in some cases a tumor rate and an age class that correspond to each other
      (high tumor rate, early tumors-low tumor rate, late tumors) are transmitted to
      the offspring, in other cases tumor rate and age class transmitted to the crosses
      diverge. 4. It seems that certain strains with very late tumors if mated with
      strains with earlier tumors have a tendency to transmit to the offspring their
      own tendency to very late tumors. With a certain strain lateness of the tumors
      seems to be dominant, while a low tumor rate is not necessarily dominant in the
      same crosses. This was noticeable in the crosses into which the strain European
      +/- 102 or 103 entered as one of the parents. 5. If both parents have a similar
      tumor rate the offspring have usually a similar tumor rate. There was, however,
      one exception to this rule in the case of the German +/- Carter mice, in which
      the offspring showed a much lower tumor rate and higher age class than either of
      the parent strains.

PMID- 19867953
TI  - THE INFLUENCE UPON THE SPLEEN AND THE THYROID OF THE COMPLETE REMOVAL OF THE
      EXTERNAL FUNCTION OF THE PANCREAS.
AB  - The complete removal of the function of the pancreas concerned in digestion is
      followed by marked changes in the spleen and in the thyroid apparatus. Second,
      the spleen shows an extreme simple atrophy. Third, the thyroid apparatus exhibits
      a constant change shown by the macroscopic transparency of the gland, by the
      microscopic increase in the amount of colloid, by the chemical increase of the
      iodine content of the gland, and by the functional test of the delayed appearance
      of tetany after the complete removal of the thyroid apparatus.

PMID- 19867954
TI  - THE INFLUENCE UPON TADPOLES OF FEEDING DESICCATED THYROID GLAND IN VARIABLE
      AMOUNTS AND OF VARIABLE IODINE CONTENTS.
AB  - We may conclude that the feeding of dried thyroid gland to tadpoles causes an
      early differentiation in proportion to the quantity fed or the percentage of
      iodine content of the gland used. With the larger doses and the higher iodine
      percentages, metabolism is stimulated to such an extent that the animals emaciate
      rapidly and die early, before there is time for much differentiation. With
      smaller amounts and lower iodine percentages the size of the animals is roughly
      inversely proportional to the amount or percentage, so that a close association
      of differentiation with pigmy size is not characteristic of thyroid feeding as
      such, as Gudenatsch seems to conclude. One may see early and marked
      differentiation along with large size. It all seems a question of dosage. The
      larger sizes are associated with slower differentiation, the smaller sizes with
      more rapid differentiation, and the smallest sizes may show no differentiation at
      all, due to the extremely rapid and marked emaciation, and early death. Non
      thyroid iodine does not have this effect. The thyroid effect is inhibited by
      exposure to cold and by cracker feeding. Exposure to cold probably acts by
      lowering metabolism; cracker feeding, by substituting food other than the
      animal's own tissues to meet the increased demands caused by the stimulating
      effect of the thyroid feeding. Gudenatsch in his earlier paper speaks of the
      thyroid as stimulating metabolism, which leads to early differentiation and
      suppresses growth. Later he seems to lean to the view that the thyroid possesses
      some specific influence on differentiation. It may all be a matter of words, but
      our present conception is that we are simply dealing with the well known action
      of thyroid on metabolism. As the iodine content increases, the thyroid
      increasingly stimulates the metabolism of the tadpole, which undergoes changes in
      size, increased growth or rapid emaciation, according to the strength of the
      action. The tadpole being a larval form, the tissues first to be stimulated to
      increased metabolism, and later the first to be consumed, are naturally those
      tissues whose normal function is approaching a normal end, and which, in the
      normal course of events, are about to undergo metamorphosis. Hastening of
      differentiation seems then to ensue not as a specific stimulation of
      differentiation, but only to be the normal result of the stimulation of general
      metabolism. The seeming specificity of the result lies not in a new action of
      thyroid, but in its application to a living organism at a specific time in its
      development. Most important, of course, is the confirmation of what we may be
      justified in regarding as an established fact; namely, that the activity and
      potency of the physiologically active substance of the thyroid is measurable in
      terms of its percentage iodine content. Finally, it may be pointed out that the
      reaction of tadpoles to thyroid feeding is so sensitive that the procedure might
      well serve as a biological test for the activity of thyroid tissue, superior even
      to chemical methods.

PMID- 19867955
TI  - EXPERIMENTAL PNEUMONIA (FRIEDLANDER TYPE).
AB  - The foregoing experiments show that in cats a definite lobar pneumonia may be
      caused by Bacillus mucosus capsulatus. Judging both from the clinical course and
      from the pathological findings, this form of pulmonary infection differs from the
      usual pneumococcus types of pneumonia and closely resembles the so called
      Friedlander's bacillus or Bacillus pneumonioe in man. In all instances in which a
      lobar pneumonia was found after the injection of the bacillus, a similar organism
      was recovered from the lung, and in no case was this associated with other
      organisms. The course of the disease in cats is very short, the animals
      developing early symptoms of profound toxemia. In 87 per cent of the animals
      showing a lobar pneumonia positive blood cultures were obtained. The pathological
      findings, judging from the early stages of the disease, are subject to
      considerable variation. In some instances the process may suggest a pseudolobar
      or confluent lobular distribution. In these cases the lung has a mottled, marble
      like appearance. In the majority of cases, however, the process gave a more
      homogeneous appearance, suggesting a diffuse and uniform distribution. Foci of
      hemorrhage were not uncommon in both. Such areas cause the mottled appearance
      sometimes found. In all instances the consolidated lung presents a greater
      infiltration of tissue than is usually seen in other types of experimental
      pneumonia. Although the exudate as seen on the cut surface may be abundant and
      especially viscid in character, this is not present in most cases. The cut
      surface of the consolidated lung does not present a granular appearance. The
      histological findings are also subject to considerable variation. In most
      instances the infundibular and alveolar spaces are completely filled with an
      exudate made up chiefly of polymorphonuclear cells. Associated with these are the
      capsulated bacilli, large vacuolated mononuclear phagocytic cells, and red blood
      cells, and occasionally small amounts of fibrin. The organisms may vary greatly
      in numbers. Some sections show spaces almost completely filled with bacilli. The
      contrast between spaces containing an exudate consisting chiefly of
      polymorphonuclear forms and an adjoining one filled with organisms is often
      striking (Fig. 4). The bacilli found are both intra- and extracellular. The large
      vacuolated cells are numerous in this type of pneumonia. They apparently are the
      first cells to become phagocytic. Often they are seen to contain as many as 10 to
      15 capsulated bacilli, while polymorphonuclear cells in the same exudate contain
      no organisms. The histogenesis of these cells seems to be somewhat clearer from
      the study of these early stages of pneumonia. In many instances one sees swollen,
      partially desquamated epithelial cells along the alveolar wall. These closely
      resemble the large vacuolated forms. Various types of these vacuolated
      mononuclear cells were observed. These may well represent stages of development
      from the desquamating epithelial cell to the large vacuolated form. Although
      similar cells may arise elsewhere, we have been led to regard them in our studies
      as epithelial in origin (Fig. 5). The number of red blood cells and the amount of
      fibrin present in the exudate vary greatly. Small foci consisting of alveolar
      spaces filled with erythrocytes are not uncommon. The fibrin is very much less
      abundant than in most types of pneumonia. From the above experiments it is seen
      that a lobar pneumonia in cats can be produced at least by two methods, either by
      intrabronchial insufflation of the organism or by direct injection into the
      veins, provided that in the latter case an irritant is introduced into the lungs.
      In each case there is little doubt but that a local injury of the lung parenchyma
      was produced. Without this injury (that is, by intravenous injection of the
      organism alone), no pulmonary lesion was obtained. Further studies with both
      these methods must be undertaken to ascertain more exactly the sequence of the
      pathological process. It seems probable that they are identical in each case. The
      results obtained from the second method employed to produce a lobar pneumonia
      offer suggestive evidence in support of a hematogenous causation of this disease
      in at least certain instances. It is not proposed to discuss the aerogenous
      versus hernatogenous theories at this time. Kidd(5) has recently reviewed the
      subject and states that the aerogenous theory for the causation of pneumonia is
      most widely held. This view has gained credence especially since the work of
      Meltzer and Lamar. In spite of this, Kidd emphasizes the fact that based on our
      knowledge of pulmonary infections in man and upon theoretical grounds and upon
      certain experimental facts, the hernatogenous theory seems more plausible. No
      definite conclusions can be drawn from the last series of experiments. From this
      limited study it seems probable that lobar pneumonic processes are produced less
      easily after intravenous injection of various cocci and insufflation of
      irritating substances than by-similar treatment with Friedlander's bacillus.

PMID- 19867956
TI  - AN EXPERIMENTAL STUDY OF BLOOD GLYCOLYSIS. THE EFFECTS OF THYROID AND ADRENAL
      EXTRACTS AND PHLORHIZIN ON GLYCOLYSIS IN VITRO.
AB  - 1. Blood glycolysis in vitro during a period of three hours' incubation proceeds
      at practically the same rate under sterile conditions and when no effort is made
      to prevent contamination. 2. Fresh thyroid extract, adrenalin, and phlorhizin do
      not contain any substances which have a constant effect upon the rate of blood
      glycolysis outside of the body. No evidence of the presence of an antiferment was
      found.

PMID- 19867957
TI  - DIET AND TUMOR GROWTH.
AB  - Lactose does not increase the receptivity of mice and rats for the transplantable
      carcinomata of their species.

PMID- 19867958
TI  - OBSERVATIONS ON ANTITYPHOID VACCINATION.
AB  - 1. Metchnikoff and Besredka's living sensitized vaccine produces a typhoid
      cholecystitis when injected directly into the gall bladder of rabbits. It is
      therefore infectious. 2. Rabbits cannot be successfully immunized with this
      vaccine against direct gall bladder infections. Accordingly, rabbits cannot be
      used to test immunity in this way. 3. The strain used in the Army vaccine is
      pathogenic, relatively avirulent, and distinctly toxic. Its efficacy is believed
      to depend on its toxicity. 4. Vaccinations in those who have had typhoid and
      revaccinations produce more severe local reactions than original vaccinations in
      some instances. 5. The typhoidin skin test is not believed to be an index of true
      immunity, but rather an indication of typhoid proteid sensitization, which is not
      so complete, so permanent, or so specific as true immunity.

PMID- 19867959
TI  - THE RELATIONSHIP OF CHRONIC PROTEIN INTOXICATION IN ANIMALS TO ANAPHYLAXIS.
AB  - Such foreign proteins as horse serum and egg-white in the amounts employed in
      these experiments do not produce evidences of intoxication immediately after
      injection into rabbits. Single large injections do, however, produce changes in
      the parenchymatous organs after a period often to twenty-one days. These develop
      at the time or immediately after the animal has formed antibodies for the foreign
      proteins. The mechanism of the development of the lesions in the myocardium,
      liver, and kidneys of rabbits is thus the same, whether a single inoculation is
      given or whether repeated inoculations are made in sensitized animals. By the
      latter method, however, much more marked and extensive changes may be produced.

PMID- 19867960
TI  - THE EFFECT OF ROENTGEN RAYS ON THE RATE OF GROWTH OF SPONTANEOUS TUMORS IN MICE.

PMID- 19867961
TI  - A FURTHER STUDY ON THE BIOLOGIC CLASSIFICATION OF PNEUMOCOCCI.
AB  - 1. At least three subgroups of Pneumococcus Type II may be recognized by specific
      immune reactions. They have been called Subgroups II A, II B, and II X. 2. That
      the organisms of these three subgroups are biologically related to Pneumococcus
      Type II is shown by the following facts: (a) Agglutination with Antipneumococcus
      Serum II. (b) Protection with Antipneumococcus Serum II, except Subgroup II X.
      (c) Absorption of Antipneumococcus Serum II with typical Type II pneumococcus
      removes the antibodies for all subgroups, (d) Absorption of Antipneumococcus
      Serum II with a member of Subgroups II A or II B removes only the antibodies for
      the homologous subgroup. Absorption of Antipneumococcus Serum II with any given
      member of Subgroup II X removes the antibodies for that particular strain only.
      3. That the three subgroups, although biologically related to Pneumococcus Type
      II, possess, nevertheless, specific differential characterswhich separate them
      one from another, is evidenced by thefollowing facts: (a) The organisms of any
      subgroup are not agglutinated bythe antisera of the other two subgroups. (b) They
      are not protected against by the sera of the other subgroups. (c) They do not
      absorb from Antipneumococcus Serum II the specific immune bodies of the other
      subgroups. 4. Subgroups II A and II B are characterized by immunity reactions
      identical within the respective group. 5. Subgroup II X consists of heterogeneous
      strains which do not cross in their immunity reaction with each other or with
      Subgroups II A or II B.

PMID- 19867962
TI  - SPONTANEOUS AND EXPERIMENTAL LEUKEMIA OF THE FOWL.
AB  - 1. The spontaneous occurrence of myeloid leukemia of the fowl is confirmed 2.
      Myeloid leukemia of the fowl is transmissible by intravenous or intraperitoneal
      injection of an organic emulsion. The latter is in confirmation of the work of
      Ellermann and Bang (6, 7), who first successfully transmitted the disease. They
      were followed by Hirschfeld and Jacoby (13)) whose successful transmissions,
      however, seem to be limited to a strain which had its origin in a fowl presented
      to them by Ellermann and Bang. Burckhardt (14, 15) likewise transmitted the
      disease, but here again the stock animal came from Hirschfeld and Jacoby and
      therefore indirectly from Ellermann and Bang. The transmission reported above is
      of special interest, because it originated in an animal absolutely unrelated to
      that of the previous investigators.

PMID- 19867963
TI  - IMMUNOLOGICAL STUDIES IN PNEUMONIA.
AB  - The serum derived from human cases of pneumonia has been used to sensitize guinea
      pigs passively. As antigen an autolysate of a pneumococcus culture was employed.
      By means of Dale's method it has been possible to show with considerable
      regularity that the blood contains sensitizing antibodies during the course of
      pneumonia, but none after the crisis. Patients suffering from other diseases have
      failed to give this reaction, as have also normal individuals.

PMID- 19867965
TI  - NOTE ON A SKIN REACTION IN PNEUMONIA.

PMID- 19867964
TI  - A QUANTITATIVE ANALYSIS OF THE INFLUENCE OF THE SIZE OF THE DEFECT ON WOUND
      HEALING IN THE SKIN OF THE GUINEA PIG.
AB  - 1. The larger the wound, the more rapidly the tongue enlarges and the earlier the
      closure of the wound takes place. Larger wounds heal, therefore, more quickly
      than smaller wounds within the variations in the size of the wound chosen in our
      experiments. 2. Both outgrowing of the tongues and contraction of the wound are
      concerned in the closing of the wound. A marked contraction sets in in the period
      preceding the closing of the wound and continues over a longer period with
      gradually diminishing intensity. The contraction, therefore, sets in earlier in
      the larger wounds. The contraction is also absolutely greater in the larger
      wound. 3. During wound healing the mitoses increase first markedly in the old
      epithelium and only very few mitoses can be found in the outgrowing epithelium
      during the first two days. Very soon the mitotic proliferation extends to the
      tongue and the number of proliferating cells may here become greater than in the
      old epithelium. With the closure of the wound a sudden fall in the number of
      mitoses takes place in both series. This fall is greatest in the tongue.
      Throughout the time of observation the number of mitoses is greater in the
      smaller wound. The fall in the number of mitoses directly after the closure of
      the wound is more sudden in the 4 mm. than in the 2 mm. series. It is, however,
      possible that the increase of mitoses extends over a larger area in the 4 mm.
      series than in the 2 mm. series. 4. It is probable that the difference in the
      rapidity in the outgrowth of the epidermal tongues and the resulting difference
      in the time of closure are mainly responsible for the difference in the
      variations in mitoses in the larger and smaller wounds. The longer the period of
      time over which the pull of the epithelium extends, the greater is the number of
      mitoses in this area. Therefore it is greater in the 2 mm. series. Closure of the
      wound is followed by a sudden decline in the number of mitoses especially in the
      area of the defect. Therefore the number of mitoses decreases earlier in the 4
      mm. series, and we find here the smallest number of mitoses during the whole
      period of our observation. 5. The size of the epithelial cell and nucleus
      increases soon after the making of the wound. A maximum is reached in both the
      larger and smaller wound in the period just preceding the closure of the wound;
      this maximum is therefore reached earlier in the larger wound. Absolutely the
      maximal size reached in both kinds of wounds is approximately the same or only a
      little higher in the larger wounds. After the closure of the wound a sudden
      decline in the cell size takes place in the larger as well as in the smaller
      wounds. Then a more gradual decline sets in. Fourteen days after the operation
      the cells are still larger than in the normal skin. The variations in the size of
      the nucleus are similar to those in the whole cell, but less marked. The curves
      of variations in cell and nuclear size follow in both the larger and smaller
      wounds a curve similar to the variations in the number of mitoses. But the cell
      size returns more slowly to the normal condition than the number of mitoses. 6.
      The closure of the wound causes an increase in the number of epithelial rows over
      the defect. This increase is therefore reached at an earlier period in the larger
      wound. The increase is greater in the larger wound owing to the greater pressure
      which the two opposing cell layers exert upon each other in the larger wound. In
      the old epithelium the maximum in the number of cell rows is apparently reached
      slightly before the closure of the wounds. It seems that the epithelial movements
      leading to the closure of the wound start in the old epithelium and extend wave
      like towards the wound. 7. It thus appears that the primary process in the wound
      healing consists in movements of the epidermis towards the wound, that these
      movements are carried out with greater energy in the case of the larger wounds,
      that the pull of the epithelium calls forth mitotic cell division, and that
      pressure exerted by epithelial cells upon each other leads to a rapid diminution
      in the mitotic proliferation.

PMID- 19867966
TI  - INTESTINAL OBSTRUCTION : V. PROTEOSE INTOXICATION.
AB  - A definite intoxication develops as a result of a closed intestinal loop and
      toxic material accumulates in the closed loops. Much evidence has been submitted
      to show that this loop poison causes the intoxication observed after producing a
      closed intestinal loop. Sufficient evidence has been presented to prove that the
      essential poison is present in these closed intestinal loops, and usually in
      concentrated form. Chemical study of the contents of closed intestinal loops
      shows that a single substance or group of substances possesses toxic properties.
      This resists autolysis and pancreatic and ereptic digestion. It is thrown out of
      solution by five volumes of alcohol or by half saturation with ammonium sulphate.
      It is readily soluble in water and is not injured by boiling. It is not removed
      by dialysis. The method of isolation excludes practically all substances except
      primary proteoses. The characteristic resistance to digestive enzymes suggests a
      heteroproteose. Proteose intoxication in dogs gives a picture identical with that
      described after poisoning with intestinal loop fluid: early salivation and
      vomiting, followed by diarrhea and prostration, fall in temperature and blood
      pressure, and finally death in collapse. Autopsy shows essentially a splanchnic
      paralysis and remarkable engorgement of liver and spleen, but especially of the
      mucosa of the duodenum and small intestine. The blood shows great concentration
      due to loss of fluid and may remain incoagulable because of an excess production
      of antithrombin. Proteoses escaping from the blood are excreted in the urine.
      This toxic proteose concerned in intestinal obstruction has not yet been isolated
      in the urine, but may be excreted by the kidneys. This probably explains the
      clinical improvement and lessened intoxication noted after transfusion.
      Experimental evidence points to a primary proteose as the essential poison
      concerned in the intoxication of closed intestinal loops and intestinal
      obstruction.

PMID- 19867967
TI  - ICTERUS : A RAPID CHANGE OF HEMOGLOBIN TO BILE PIGMENT IN THE PLEURAL AND
      PERITONEAL CAVITIES.
AB  - It is known that hemoglobin can be rapidly changed to bile pigment in a
      circulation confined to the head, neck, and thorax. This excludes direct liver
      participation (1). These experiments show that hemoglobin can be changed to bile
      pigment within the pleural or peritoneal cavities. This transformation can
      usually be detected after eight hours, and the amount can often be estimated
      quantitatively after an interval of twenty-four hours. Such experiments
      demonstrate the importance which may attach to extrahepatic bile pigment
      formation. That bile pigments can be formed without direct liver activity is
      established beyond doubt.

PMID- 19867968
TI  - AN EXPERIMENTAL STUDY OF THE EFFECT OF CHOLE-CYSTGASTROSTOMY ON GASTRIC ACIDITY.
AB  - It has been shown that small amounts of the digestive secretions normally present
      in the duodenum regurgitate into the stomach following operative anastomosis
      between the stomach and the upper intestinal tract. As the duodenal contents are
      alkaline in reaction this reflux is thought by many to result in a decrease in
      the acidity of the gastric contents. The purpose of the investigations reported
      here has been to determine the effect of bile on the acid chyme of the stomach.
      By means of a cholecystgastrostomy with ligation and division of the common bile
      duct in six dogs the bile was diverted from the duodenum into the stomach. The
      secretion of gastric juice and the acidity of the gastric contents throughout the
      period of digestion were followed before and after the anastomoses. For this
      purpose three of the dogs were provided with Pawlow stomach pouches. In the three
      remaining animals the test meals were recovered by using apomorphin injections.
      The results from the two series of experiments agree. They indicate, at least
      with a diet of meat and water, that bile when it is present in the stomach
      throughout the course of digestion has no appreciable effect on the acidity of
      the gastric contents. While the anastomosis of the gall bladder to the stomach
      occasioned some temporary anorexia and vomiting in two of the dogs, the four
      remaining animals bore the operation well. Three or four weeks subsequent to the
      operation the digestion and the nutrition appeared normal in each instance.
      Postmortem examinations revealed no pathological changes in the gastric mucosa.

PMID- 19867969
TI  - A PATHOLOGICAL STUDY OF SYPHILITIC AORTITIS AND ITS SEROLOGY.
AB  - 1. Syphilitic aortitis is a productive inflammatory process, the earliest and
      most constant feature of which is a perivascular round cell infiltration in the
      adventitia. 2. The typical gross picture of luetic aortitis is often obscured by
      a superimposed, diffuse atherosclerosis. In the early cases the aorta appears
      fairly normal, presenting only the characteristic histological changes. 3. A pure
      aortic insufficient valve, with the exception of an infectious endocarditis, is
      always luetic. 4. Cardiac hypertrophy is not a complication of luetic aortitis.
      When present it is usually associated with a nephritis. 5. The demonstration of
      Spirochoeta pallida, even in advanced specimens of syphilitic aortas, is
      doubtful. 6. An antigen prepared from alcoholic extract of guinea pig heart with
      the original Wassermann technique should be preferred in diagnosing luetic
      aortitis. 7. Positive complement fixations in patients suffering with syphilis
      for a period of about fifteen years or longer suggest the probability, at least,
      of histological luetic changes in the aorta in 80 to 90 per cent of the cases. 60
      per cent of these die from aortitis. 8. About 94 per cent of patients suffering
      with aortitis give positive Wassermann reactions.

PMID- 19867970
TI  - THE ETIOLOGY OF RAT-BITE FEVER.
AB  - The similarity in the cases of rat-bite fever recorded in the literature
      establishes it as a definite clinical entity. The same symptomatology occurs in
      cases from Asia, Europe, and America. The greater frequency of the disease in
      Japan than elsewhere is probably due to the housing conditions and habits of the
      people resulting in the more frequent occurrence of rat-bites. It does not seem
      necessary to consider that cases occurring in Europe and America are due to the
      bites of rats that have been imported from Japan. The clinical picture and course
      of the disease indicate that it is infectious in origin. Until Schottmuller's
      case appeared in 1914, the etiology had been undiscovered. He isolated from his
      case in eight consecutive blood cultures a streptothrix which he has designated
      Streptothrix muris ratti. His work has been confirmed by the isolation of an
      identical streptothrix from the blood during life and at autopsy in the case here
      reported. Further confirmation of the etiological relationship of this organism
      to the infection in our patient is found in the production of powerful
      agglutinins for the organism in the blood serum of this case and in the
      demonstration of the organism in the vegetation on the mitral valve. It is not
      unreasonable to suppose that Proescher (13) observed the same organism in the
      sections of the excised wound in his case. Although it is fully realized that
      Koch's postulates have not been fulfilled in the absence of successful animal
      experimentation, nevertheless the accumulated evidence here presented leaves
      little reason to doubt that the specific cause of rat-bite fever is Streptothrix
      muris ratti. The pathology of rat-bite fever has hitherto been largely a matter
      of surmise. One autopsy only has been recorded in the literature (Miura (22)),
      and nothing abnormal was noted other than injection of the pial vessels. The
      autopsy in the case here reported has proved of considerable interest in the
      extent and character of the lesions found. A streptothrix septicemia with the
      localization of the organism in the mitral valve producing an acute ulcerative
      endocarditis is the most striking feature of the case. The infarcts of the spleen
      and kidney are a natural sequence of the endocarditis. The subacute lesions of
      the myocardium, liver, adrenal, and kidneys, glomerular and interstitial, are all
      of a similar nature, consisting of areas infiltrated with leukocytes,
      lymphocytes, plasma, and endothelial cells with varying degrees of degeneration
      of the normal cells of the affected area. In no instance has the presence of the
      streptothrix in these lesions been demonstrated, and it is not unreasonable to
      assume that they are toxic in origin. The data here presented may be correlated
      with the clinical features of rat-bite fever to give us a clear understanding of
      the course and nature of the disease. The patient is inoculated by the bite of a
      rat with Streptothrix muris ratti. After a variable incubation period a non
      suppurative inflammatory reaction occurs at the site of the wound with extension
      to the neighboring lymphatics and lymph nodes. Invasion of the blood stream
      follows, accompanied by the onset of severe toxic symptoms. Clinically the
      nervous system and frequently the kidneys seem to be especially involved. That
      the myocardium, liver, and adrenals may also suffer is shown by the autopsy
      findings in the case reported above. Ulcerative endocarditis is probably a rare
      occurrence. In the majority of cases after a more or less prolonged course, the
      disease terminates spontaneously and so may be considered a self-limited
      infection. This is presumably brought about by the development in the body of a
      protective mechanism against the streptothrix. That such a process does occur is
      evidenced by the demonstration of agglutinins in our case. Whether a permanent
      immunity is acquired after one attack of rat-bite fever is not known. No
      instances of a second infection are recorded in the literature. Although rat-bite
      fever varies somewhat in its symptomatology in individual cases, the picture is
      sufficiently characteristic to make the diagnosis not a difficult matter. The
      history of a rat-bite, latent incubation period with subsequent non-suppurative
      inflammatory reaction of the wound, lymphangitis, and enlarged lymph nodes,
      severe chill at onset, high fever of the relapsing type, intense muscular pain
      and nervous symptoms, and the characteristic bluish red exanthem, present a
      symptom-complex not easily overlooked. The disease is frequently complicated by a
      severe nephritis, and prolonged cases develop a high grade of anemia and
      cachexia. In the case here reported ulcerative endocarditis occurred. In the
      large majority of cases the prognosis is favorable for a successful termination.
      The patients, however, are often incapacitated for a considerable period of time
      The mortality is about 10 per cent, death usually occurring in the first febrile
      period apparently from a profound toxemia, or at a later stage due to the
      development of a severe nephritis. Until recently treatment has been entirely
      symptomatic and has been of little avail in altering the course of the disease.
      Miyake has found immediate treatment of the wound by cauterization or with
      carbolic acid highly efficient as a prophylactic measure. Hata (30) in 1912
      introduced salvarsan therapy and reported eight cases so treated, seven of which
      showed marked and rapid improvement. One case was apparently unaffected. Two of
      the cases receiving only small doses had a subsequent relapse. Surveyor (31) and
      Dalal (18) also have reported success with salvarsan injections. It is to be
      hoped that further experience with this method of treatment will yield equally
      favorable results.

PMID- 19867971
TI  - ANTIBLASTIC IMMUNITY.
AB  - 1. Antipneumococcus serum possesses the power of inhibiting for a certain period
      of time the multiplication of pneumococci. 2. It also has the capacity of
      inhibiting the proteolytic and glycolytc functions of pneumococci. 3. This power
      is acquired for the first time or appears in increased amounts in human serum at
      the time of crisis in lobar pneumonia. 4. The retardation of bacterial growth is
      thought to be dependent upon the inhibition of metabolic function due to the
      presence of anti-enzymotic substances in antipneumococcus serum. To this
      phenomenon we have applied the term antiblastic immunity.

PMID- 19867972
TI  - ATHEROMA AND OTHER LESIONS PRODUCED IN RABBITS BY CHOLESTEROL FEEDING.
AB  - The feeding of egg yolk or pure cholesterol to rabbits produces an abundant
      deposit of anisotropic fat in various organs. From this deposit characteristic
      lesions secondarily result in certain organs. Prominent among these lesions is an
      atheroma of the aorta very similar in the gross and histologically to the human
      lesion. Lesions of other vessels are also produced, conspicuous among which are
      those of the branches of the pulmonary artery. There is a large deposit of
      anisotropic fat in the liver which produces a cirrhosis. Enlargement of the
      adrenals occurs, probably due to the storage of an excessive amount of
      anisotropic fat. In a certain proportion of rabbits conspicuous lesions are
      produced in the kidneys consisting of nodular deposits of anisotropic fat in the
      medullary portion, the fat being contained for the most part in endothelial cells
      and fibroblasts in the interstitial tissue. Later softening occurs in these areas
      as in the aorta; the cells break down; there is an abundant deposit of
      cholesterol crystals, some calcification, and a proliferation of connective
      tissue. Scars frequently extend outward from these lesions through the cortex,
      but the nodular deposits of anisotropic fat are never seen in the cortex. It is
      impossible to determine definitely from these experiments whether or not these
      deposits are dependent on preexisting interstitial lesions.

PMID- 19867973
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : XIV. CHANGES IN THE BLOOD FOLLOWING DIVERSION OF THE SPLENIC BLOOD
      FROM THE LIVER. A CONTROL STUDY OF THE EFFECTS OF SPLENECTOMY.
AB  - 1. In dogs whose splenic veins have been ligated or transplanted into the
      inferior vena cava, or in which an Eck fistula has been made, an anemia occurs
      which resembles that following splenectomy and shows the same general variation
      in degree and duration. 2. The resistance of the red cells to hypotonic salt
      solution is quickly increased, sometimes coincident with and sometimes preceding
      the anemia. As a rule, it gradually returns to normal in about the same length of
      time as it takes the anemia to disappear, but may remain increased for longer
      periods. 3. There is an initial leukocytosis, involving at first the
      polymorphonuclear leucocytes and transitional cells. As the total leukocytosis
      diminishes there is both a relative and actual increase of small lymphocytes and
      usually of eosinophils. This may either be temporary or last during the rest of
      the period of observation and differs from the ordinary postoperative
      leukocytosis. 4. Ligation of the splenic vein is followed by considerable atrophy
      of the spleen, but not by necrosis or thrombosis. There is rarely adequate new
      vein formation. The other operations cause little or no change in the spleen. 5.
      Whether the disturbances as described are due to the loss of a certain volume of
      blood to the liver, or, as has been previously suggested, to the loss of a
      splenic hormone, it is impossible to say. If the former is true, the method of
      production of the anemia still remains unexplained. It is evident, furthermore,
      that the latter theory has also no value unless it is assumed that this hormone
      must be activated by passage through the liver.

PMID- 19867974
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : XV. THE RESISTANCE TO HEMOLYTIC AGENTS OF DOGS IN WHICH THE SPLENIC
      BLOOD HAS BEEN DIVERTED FROM THE LIVER.
AB  - 1. Dogs whose splenic veins or portal vein (Eck fistula) have been transplanted
      into the inferior vena cava, or whose splenic veins have been ligated, show a
      lessened tendency to jaundice similar to that exhibited by splenectomized
      animals. 2. Although the previously existing anemia and the concomitant increased
      resistance of the red cells of these animals are undoubtedly factors in the
      greater resistance to hemolytic agents, the lessened tendency to jaundice is, in
      part at least, due to a mechanical factor dependent on the course of the blood
      supply to the liver. 3. The additional anemia caused in the test animals by
      hemolytic agents is usually less than in the controls, although the total fall
      from the original normal may be greater. This applies to the splenectomized as
      well as the other test animals and is a modification of our former statements in
      regard to the severity of the anemia in splenectomized dogs. 4. Although the
      destruction of blood in these animals is less than in the normal controls, the
      repair of the same takes considerably longer than in the controls. This confirms
      similar results previously obtained in splenectomized animals. 5. The white cells
      exhibit much the same changes as they do following the administration of
      hemolytic agents to splenectomized or normal animals. As these changes are not
      unlike those following uncomplicated splenectomy or the operations here
      discussed, they cannot be considered as characteristic of any of the above
      procedures, but perhaps as an accompaniment of any temporary increased blood
      destruction. 6. The reaction of test and control animals is substantially the
      same, whether the jaundice is caused by toluylenediamin or hemolytic immune
      serum.

PMID- 19867975
TI  - THE PATHOLOGICAL EFFECTS OF ATMOSPHERES RICH IN OXYGEN.
AB  - In spite of numerous abnormalities or non-experimental lesions in the rabbit
      certain facts can be considered as established. It has been known for many years
      that pneumonia is produced by the more or less prolonged inhalation of high
      partial pressures of oxygen. The studies herein reported show that atmospheres
      containing 80 to 96 per cent oxygen under normal barometric pressure produce in
      24 hours, or more commonly 48 hours, congestion, edema, epithelial degeneration
      and desquamation, fibrin formation, and finally a pneumonia, probably of
      irritative origin and to be described as a fibrinous bronchopneumonia. The
      important new points are the time relations of these changes and definition of
      the type of the pneumonia. Other studies have noted slight passive congestion,
      but it is now established that this is to be accounted for in most cases by
      dilatation of the right side or of both sides of the heart. This congestion
      affects all the abdominal viscera and is accompanied by certain secondary changes
      such as cloudy swelling of the parenchymatous organs and phagocytosis of
      erythrocytes by endothelial cells of the mesenteric lymph nodes. Although
      deficiency of oxygen may affect the hematopoietic system, the animals subjected
      to high oxygen percentages failed to show any demonstrable pathologic changes in
      blood, spleen, lymph nodes, or bone marrow, except for the presence of
      congestion. This study is the first of a comprehensive series projected in and
      under the direction of the Carnegie Nutrition Laboratory. Different animals and
      various methods of attack will be employed in the investigation.

PMID- 19867976
TI  - THE INHIBITION OF THE TOXICITY OF URANIUM NITRATE BY SODIUM CARBONATE, AND THE
      PROTECTION OF THE KIDNEY ACUTELY NEPHROPATHIC FROM URANIUM FROM THE TOXIC ACTION
      OF AN ANESTHETIC BY SODIUM CARBONATE.
AB  - 1. The toxicity of uranium in animals of different ages is associated with the
      power of the metal to lead to the formation of organic acids, as, for instance,
      diacetic acid and also acetone. 2. The power of sodium carbonate to lessen the
      toxicity of uranium depends upon its power to delay the formation of such bodies
      and to cause their appearance in the urine in lessened amounts, and does not
      depend upon the power of the carbonate to detoxicate the metal. 3. The protection
      of the kidney by the carbonate, which is shown by the kidney being functionally
      much more active during an anesthesia than the kidney of a control animal, and by
      the Jack of fatty degeneration, acute swelling, and necrosis of the renal
      epithelium which is constantly seen in the unprotected kidneys, is probably
      dependent upon two factors: the neutralization of organic acids formed prior to
      and during the anesthesia, and the neutralization of hydrochloric acid which
      Graham has shown to be liberated by chloroform during an anesthesia induced by
      this substance.

PMID- 19867977
TI  - INTRATESTICULAR IMPLANTATION OF THE FLEXNER-JOBLING RAT CARCINOMA.
AB  - The Flexner-Jobling adenocarcinoma of the rat is easily transplantable into the
      testis of this animal. The resulting growths in the intact testis do not often
      attain the size of subcutaneous tumors. The smaller size of intratesticular
      nodules can not be explained solely by the pressure to which they are subjected
      during their growth; other factors, which cannot be determined, appear to be
      concerned.

PMID- 19867978
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT PRODUCED BY THE BRAIN SUBSTANCE OF THE LIVING
      PARETIC.
AB  - 1. Spirochaetes from the living paretic brain easily infect rabbits with
      experimental syphilis. 2. They constitute a virulent strain with a shorter period
      of incubation for the rabbit than exists with other strains.

PMID- 19867979
TI  - A STUDY OF THE GASTRIC ULCERS FOLLOWING REMOVAL OF THE ADRENALS.
AB  - Acute ulcers of the gastric mucosa are found in a large percentage of dogs and
      cats dying after adrenalectomy. These ulcers seem to develop during the moribund
      period. They are apparently peptic ulcers forming at the site of local
      hemorrhages in the gastric mucosa. They are true acute ulcers, usually
      penetrating to the muscularis mucosa with a total loss of epithelium. They
      develop in the absence of pancreatic secretion and bile. However, they appear to
      develop only in an acid medium.

PMID- 19867980
TI  - A TRANSPLANTABLE CARCINOMA OF THE GUINEA PIG.
AB  - An adenocarcinoma of the mammary gland of an old guinea pig has been successfully
      transplanted through eight successive series of animals. It now appears much
      earlier and grows more rapidly. The number of takes also has increased. In two
      instances metastasis to the regional lymph glands (inguinal) has been observed.
      Once microscopic metastases were found in the kidney. The so called precancerous
      changes observed in the breasts of women and mice suffering from mammary
      carcinoma were found in the mammary gland of the spontaneous tumor animal. It is
      hoped that the tumor may soon be utilized for experimental purposes.

PMID- 19867981
TI  - THE PRESERVATION OF LIVING RED BLOOD CELLS IN VITRO : I. METHODS OF PRESERVATION.
AB  - The erythrocytes of some species are much damaged when handled in salt solutions,
      as in washing with the centrifuge after the ordinary method. The injury is
      mechanical in character. It may express itself in hemolysis only after the cells
      have been kept for some days. It is greatest in the case of dog corpuscles, and
      well marked with sheep and rabbit cells. The fragility of the red cells, as
      indicated by washing or shaking them in salt solution is different, not only for
      different species, but for different individuals. It varies independently of the
      resistance to hypotonic solutions. The protection of fragile erythrocytes during
      washing is essential if they are to be preserved in vitro for any considerable
      time. The addition of a little gelatin ((1/8) per cent) to the wash fluid
      suffices for this purpose, and by its use the period of survival in salt
      solutions of washed rabbit, sheep, and dog cells is greatly prolonged. Plasma,
      like gelatin, has marked protective properties. Though gelatin acts as a
      protective for red cells it is not preservative of them in the real sense. Cells
      do not last longer when it is added to the fluids in which they are kept. Locke's
      solution, though better probably than Ringer's solution, or a sodium chloride
      solution, as a medium in which to keep red cells, is ultimately harmful. The
      addition of innocuous colloids does not improve it. But the sugars, especially
      dextrose and saccharose, have a remarkable power to prevent its injurious action,
      and they possess, in addition, preservative qualities. Cells washed in gelatin
      Locke's and placed in a mixture of Locke's solution with an isotonic, watery
      solution of a sugar remain intact for a long time,-nearly 2 months in the case of
      sheep cells. The kept cells go easily into suspension free of clumps, they pass
      readily through paper filters, take up and give off oxygen, and when used for the
      Wassermann reaction behave exactly as do fresh cells of the same individual. The
      best preservative solutions are approximately isotonic with the blood serum. If
      the cells are to be much handled gelatin should be present, for the sugars do not
      protect against mechanical injury. Different preservative mixtures are required
      for the cells of different species. Dog cells last longest in fluids containing
      dextrin as well as a sugar. The mixture best for red cells is not necessarily
      best for leukocytes. A simple and practical method of keeping rabbit and human
      erythrocytes is in citrated whole blood to which sugar solution is added. In
      citrated blood, as such, human red cells tend to break down rather rapidly, no
      matter what the proportion of citrate. Hemolysis is well marked after little more
      than a week. But in a mixture of 3 parts of human blood, 2 parts of isotonic
      citrate solution (3.8 per cent sodium citrate in water), and 5 parts of isotonic
      dextrose solution (5.4 per cent dextrose in water), the cells remain intact for
      about 4 weeks. Rabbit red cells can be kept for more than 3 weeks in citrated
      blood; and the addition of sugar lengthens the preservation only a little. The
      results differ strikingly with the amount of citrate employed. Hemolysis occurs
      relatively early when the smallest quantity is used that will prevent clotting.
      The optimum mixture has 3 parts of rabbit blood to 2 of isotonic citrate
      solution. In the second part of this paper experiments are detailed which prove
      that cells preserved by the methods here recorded function excellently when
      reintroduced into the body.

PMID- 19867982
TI  - THE PRESERVATION OF LIVING RED BLOOD CELLS IN VITRO : II. THE TRANSFUSION OF KEPT
      CELLS.
AB  - In order to determine the availability for functional uses of red cells kept in
      vitro by our methods, transfusion experiments have been carried out with rabbits
      by which a large part of their blood was replaced with kept rabbit cells
      suspended in Locke's solution. It has been found that erythrocytes preserved in
      mixtures of blood, sodium citrate, saccharose, and water for 14 days, and used to
      replace normal blood, will remain in circulation and function so well that the
      animal shows no disturbance, and the blood count, hemoglobin, and percentage of
      reticulated red cells remain unvaried. Cells kept for longer periods, though
      intact and apparently unchanged when transfused, soon leave the circulation.
      Animals in which this disappearance of cells is taking place on a large scale,
      remain healthy save for the progressing anemia. The experiments prove that, in
      the exsanguinated rabbit at least, transfusions of cells kept for a long time in
      vitro may be used to replace the blood lost, and that when the cells have been
      kept too long but are still intact they are disposed of without harm. The
      indications are that kept human cells could be profitably employed in the same
      way.

PMID- 19867983
TI  - THE CAUSE OF RAT-BITE FEVER.

PMID- 19867984
TI  - A CONTRIBUTION TO THE BIOLOGY OF PERIPHERAL NERVES IN TRANSPLANTATION : II. LIFE
      OF PERIPHERAL NERVES OF MAMMALS IN PLASMA.
AB  - 1. The Wallerian degeneration occurring in peripheral nerves by incubation in
      Ringer solution and serum does not occur in plasma. 2. Peripheral nerves
      incubated in plasma give rise to no growth. The same is true of peripheral nerves
      in a Wallerian degeneration up to the 4th day. 3. Peripheral nerves in Wallerian
      degeneration from the 5th day give rise to a growth of the syncytium of Schwann.
      In cultures from later stages there is a progressive growth of the same
      structure. It is evident that the proliferation of the cells of Schwann is
      directly produced by the degeneration of the axis cylinder and its myelin sheath.
      4. In no case was growth of axis cylinders observed. 5. The growth of the
      syncytium of Schwann from degenerating nerves affords a basis for an anatomical
      conception of the centrifugal orientation of growing axis cylinders in
      regeneration. 6. Morphologically there is a striking resemblance between the
      syncytium of Schwann and neuroglia growing in plasma.

PMID- 19867985
TI  - THE REACTIONS BETWEEN BACTERIA AND ANIMAL TISSUES UNDER CONDITIONS OF ARTIFICIAL
      CULTIVATION : II. BACTERICIDAL ACTION IN TISSUE CULTURES.
AB  - The results here reported confirm those of the former papers and strengthen the
      conclusions drawn therefrom. They may be summarized as follows: Chicken plasma
      has a marked bactericidal action on Bacillus typhosus, which may be in some
      slight degree overcome by the presence of growing tissue, especially splenic
      tissue, in the cultures. On Bacillus dysenterioe this bactericidal action of
      chicken plasma is present, but much less marked, and the same counteracting
      action of tissue, especially splenic tissue, is evident. On Bacillus coli verus
      chicken plasma has little or no bactericidal action. On Bacterium diphtheriticum
      chicken plasma has a very strong bactericidal action which may be strongly
      counteracted by the presence of growing tissue in the cultures. In all cases the
      bactericidal action of the plasma is decidedly diminished by dilution, as shown
      by the comparative results of these and the cultures formerly reported. The
      migrating white cells from splenic cultures, or substances closely associated
      with these cells, have a distinctly bactericidal influence on all organisms
      tested except Bacillus coli verus. Murphy states that lymphocytes first appear in
      the general circulation of the chick embryo on the 18th to 20th day, but in my
      cultures of splenic tissue cells resembling lymphocytes in morphology and
      behavior begin to appear in cultures of 11 or 12 day spleen and are abundant in
      cultures of spleen from 14 day or older embryos.

PMID- 19867986
TI  - THE REACTIONS BETWEEN BACTERIA AND ANIMAL TISSUES UNDER CONDITIONS OF ARTIFICIAL
      CULTIVATION : III. THE ACTION OF BACTERIAL VACCINES ON TISSUE CULTURES IN VITRO.
AB  - These results seem to indicate that many bacteria may be utilized by tissue cells
      as food for growth or may contain a substance or substances stimulating cell
      growth or multiplication. This substance is stable and is not destroyed by
      heating to 100 degrees C. or by long standing. With Micrococcus aureus this
      action is often neutralized or overcome by a substance inhibitory to growth. The
      nature of these substances has not yet been determined, though several attempts
      along this line were made by endeavoring to split the typhoid bacterial substance
      according to the method of Vaughan See PDF for Structure and testing the
      poisonous and non-poisonous residues separately. However, at the time too little
      bacterial substance was used to obtain enough end-products to be of much use, and
      the products so obtained prevented the plasma from coagulating. Even in the
      uncoagulated plasma there appeared to be an increase of cells in the cultures
      with the non-poisonous residue. The author hopes to be able to repeat these tests
      with split products at a later time when more bacterial substance is available,
      with the hope of obtaining more definite results.

PMID- 19867987
TI  - THE REACTIONS BETWEEN BACTERIA AND ANIMAL TISSUES UNDER CONDITIONS OF ARTIFICIAL
      CULTIVATION : IV. THE CULTIVATION OF TUBERCLE BACILLI WITH ANIMAL TISSUES IN
      VITRO.
AB  - In plasma cultures, with or without tissue, tubercle bacilli form characteristic
      streptothrix-like colonies of loosely twisted skeins of threads. In plasma tissue
      cultures embryonal connective tissue and epithelial cells phagocytyze tubercle
      bacilli freely. Splenic tissue cultures from fourteen day or older embryos if
      inoculated with isolated bacilli will phagocytyze and prevent the development of
      all or nearly all bacilli present. If heavy inoculations of tubercle bacilli with
      many bacillary clumps are made in splenic cultures the bacilli develop more
      freely than in similar connective tissue cultures from heart tissue in spite of
      marked phagocytosis. In such cultures the first change seen is a clustering of
      small round cells, interpreted as lymphocytes, around bacillary clumps and
      colonies followed by a similar clustering of larger parenchymatous polygonal
      cells with one or several nuclei, interpreted as epithelioid cells, which
      phagocytyze any bacilli with which they may come in contact. The larger cells
      containing bacilli then fuse to form larger multinuclear cells and these by
      further fusion form typical giant cells with quiescent nuclei in characteristic
      groupings and bacilli in degenerated protoplasm away from the nuclear groups.
      Cells which have phagocytyzed bacilli may digest them or may be unable to do so,
      in which case the bacilli develop within the cells and eventually cause complete
      cell degeneration.

PMID- 19867988
TI  - ABERRANT INTESTINAL PROTOZOAN PARASITES IN THE TURKEY.

PMID- 19867989
TI  - A FURTHER STUDY OF THE REGENERATED EPITHELIUM IN CHRONIC URANIUM NEPHRITIS. AN
      ANATOMICAL INVESTIGATION OF ITS FUNCTION.
AB  - 1. Definite morphological changes occur in the batonnets of the proximal
      convoluted tubule in stages of activity. 2. Atypical mitochondria but no
      batonnets exist in the regenerated cells found in chronic uranium nephritis. 3.
      No secretion of urea occurs in these cells which do not contain the cell organs.
      4. The urea is secreted normally in the proximal convoluted tubule only
      (Leschke). 5. The urea appears in the form of granules, which are arranged in
      definite rows. 6. It is suggested that the secretion of the urea is by means of
      the mitochondrial batonnets which act as condensors.

PMID- 19867990
TI  - STUDIES ON TREPONEMA PALLIDUM AND SYPHILIS : II. SPIROCHAETICIDAL ANTIBODIES
      AGAINST TREPONEMA PALLIDUM.
AB  - We believe that our experiments have shown that the serum of rabbits and sheep
      immunized with cultures of Treponema pallidum acquires spirochaeticidal
      properties for these culture spirochaetes. The normal serum of these animals also
      possesses spirochaeticidal action if used in sufficient quantities, and the
      action of the immune serum represents probably an increase of the antibodies
      normally present. Both normal and immune spirochaeticidal properties are
      destroyed by heating to 56 degrees C. The spirochaeticidal action of the immune
      serum can be reactivated by the addition of fresh normal serum of the same
      species, insufficient in amount to exert a spirochaeticidal effect by itself. The
      structure of these spirochaeticidal bodies, therefore, is entirely analogous to
      that of the well known bactericidal antibodies known to exist in antibacterial
      sera. We do not wish to have these results interpreted as applying to virulent
      spirochaetes as well as to culture spirochaetes. A subsequent publication will
      demonstrate why we specify this at present.

PMID- 19867991
TI  - STUDIES ON TREPONEMA PALLIDUM AND SYPHILIS : III. THE INDIVIDUAL FLUCTUATIONS IN
      VIRULENCE AND COMPARATIVE VIRULENCE OF TREPONEMA PALLIDUM STRAINS PASSED THROUGH
      RABBITS.
AB  - 1. As regards these strains, at least, there is no consistent change, either
      increase or decrease, of rabbit pathogenicity during progressive rabbit passage.
      2. There is no difference in pathogenicity between these different strains,
      although some of them were isolated from condylomata, some from chancres, one
      from a mucous patch, and one by Nichols from the nervous system. 3. We do not
      believe that there is any consistency of difference in speed of incubation
      between these various strains. 4. We think that the nature of the lesion produced
      by any individual strain, and the incubation time as well, are dependent upon the
      fortuitous factors incident to the nature of the material used, the technique of
      injection, and the size of rabbit in which the injection is made. As to the
      tendency to generalize possessed by one strain or another, we are not prepared to
      make a statement. We have not inspected as carefully as we might all our rabbits
      in regard to the more obscure syphilitic lesions such as small nodules on the
      eyebrows, nodules on the nasal bones, and internal lesions of the eye. As a
      matter of fact, we have noticed three cases of keratitis, probably syphilitic,
      and a number of preputial metastases, we have seen occasional nodules about the
      anus, and in one case a peritonitis in the fluid of which living treponemata were
      found on examination. There has not been in our series an extensive number of
      generalizations. We attribute this largely to the fact that all the studies here
      recorded were made on rabbits intratesticularly inoculated. It appears from the
      writings of other investigators that intravenous and intracardial injection of
      rabbits leads to a more extensive metastatic or general distribution. Two of the
      few rabbits inoculated intravenously showed testicular lesions. A series of
      rabbits intracerebrally inoculated through trephine openings showed nothing
      definite on autopsy, though one of them showed interference with reflexes and
      rigidity of the limbs for a time which seemed significant of pathological change.
      This rabbit, however, recovered entirely.

PMID- 19867992
TI  - STUDIES ON TREPONEMA PALLIDUM AND SYPHILIS : IV. THE DIFFERENCE IN BEHAVIOR IN
      IMMUNE SERUM BETWEEN CULTIVATED NON-VIRULENT TREPONEMA PALLIDUM AND VIRULENT
      TREPONEMATA FROM LESIONS.
AB  - Although antibodies can be produced by the immunization of animals with
      cultivated Treponema pallidum, and although these antibodies exert specific
      agglutinative and treponemicidal action upon the culture organisms, they possess,
      at least in the concentration so far obtained by us in rabbits and sheep,
      practically no action for virulent treponemata obtained directly from lesions.
      There seems to be in the infected body an inability to exert a purely serum
      action upon the virulent treponemata, a condition of affairs which may well lead
      to a lack of antigen absorption on the part of the body and a consequent failure
      to produce serum antibodies. We do not think that this should in any way
      discourage our further investigation of the protective action of antibodies
      produced with culture pallida. On the one hand, the slight occasional
      agglutination and the lower proportion of takes with the concentrated serum in
      the last experiment at least indicate the possibility that we have been working
      with sera that are not sufficiently powerful and that just as with work with the
      pneumococcus and other highly invasive organisms, a serum of considerable
      antibody contents must be used before results can be expected. Again, the
      destruction of treponemata and the healing of lesions which undoubtedly takes
      place in rabbits, sometimes with surprising speed, may be a cellular destruction,
      and by injecting the sera either locally or intravenously and giving them time to
      be absorbed by the cells before injecting virulent material, better results may
      be obtained. This direction of research as well as further studies on the
      antagonistic cellular processes against the pallida, the immunization of animals
      with killed virulent organisms, and the antibodies in rabbits and human beings
      during the course of infection and after recovery are being investigated, and we
      hope to be able to report upon them in the near future.

PMID- 19867993
TI  - AN EXPERIMENTAL STUDY OF PAROTITIS (MUMPS).
AB  - Cats injected into the parotid gland and testicle with a bacterial sterile
      filtrate of the salivary secretion of children in the active stage of parotitis
      or mumps can be made to develop a pathological condition having several points of
      resemblance to the condition present in mumps in human beings. After an
      incubation stage of from five to eight days definite changes have been noted in
      the temperature, blood leukocytes, and inoculated organs. The temperature rise
      begins within twenty-four hours of the inoculations and reaches a maximum in from
      seven to fourteen days. The febrile rise fluctuates between 1 degrees and 2.5
      degrees C. The white blood cells begin to increase on the second day following
      the inoculation. The first change is a polymorphonuclear leukocytosis which
      precedes the glandular swellings. This initial rise is followed by a decline,
      after which the lymphocytes increase. The increase is confined to the small
      lymphocytes, which increase to from 7 to 10 per cent of their initial number. The
      inoculated glands become swollen and tender. The swelling and tenderness become
      apparent from the fifth to the ninth days and persist for a variable period. The
      parotid changes are less constant or less obvious than are the testicular. The
      latter are constant and endure from eight to twelve days. The rise of temperature
      and the leukocytosis precede the glandular swelling, but all the changes reach
      the maximum at about the same time, after which they decline gradually. What may
      be regarded as normal conditions are reestablished in four weeks or less. The
      intraparotid and intratesticular injections of extracts of normal parotid gland
      and testicles may cause a mild rise of temperature and leukocytosis of brief
      duration, but swelling and tenderness are absent. The white cells increased are
      the polymorphonuclears and not the lymphocytes. The intraparotid and
      intratesticular injections of filtrates of normal saliva may cause a mild rise of
      temperature of very brief duration, but leukocytosis, swelling, and tenderness do
      not appear. The histological changes in the parotid gland when present consist
      chiefly of edema of the interlobular connective tissue with mononuclear
      interstitial infiltration about the ducts and elsewhere. In cases of long
      duration the ducts may be dilated. But in some instances the swollen gland while
      showing congestion and edema in gross showed inconspicuous changes under the
      microscope. The histological changes in the testicle are of two kinds: inconstant
      changes of cellular invasion between the tubules and swelling or even
      multiplication of the interstitial cells, constant ones consisting of
      degeneration of the epithelium and interference with spermatogenesis, a condition
      to which we have applied the term "spermatorrhexis." The pathological conditions
      set up by the filtrate derived from the salivary secretion of cases of acute
      parotitis are intensified by successive transfers through a small series of cats
      of the extract and emulsion of the parotid gland and testicle previously
      inoculated. The pathological changes are also prevented or reduced when the
      extract or emulsion is previously incubated with a quantity of blood serum
      obtained from a cat which has survived inoculation. Normal serum, on the other
      hand, has no such inhibiting effect. The deduction from these experiments is to
      the effect that the salivary secretion in parotitis or mumps contains a
      filterable substance capable of setting up a series of definite pathological
      conditions when inoculated into the testicle and parotid glands of cats. Whether
      this active material is a microorganism and if so whether it is the specific
      microbic cause of parotitis or mumps remains to be ascertained.

PMID- 19867994
TI  - THE ETIOLOGY, MODE OF INFECTION, AND SPECIFIC THERAPY OF WEIL'S DISEASE
      (SPIROCHAETOSIS ICTEROHAEMORRHAGICA).

PMID- 19867995
TI  - A METHOD FOR THE RAPID PREPARATION OF ANTIMENINGITIS SERUM.
AB  - Potent antimeningitis serum can be safely produced in the horse by the method of
      three successive intravenous inoculations of living meningococci and
      parameningococci repeated at stated intervals. Sudden and alarming symptoms and
      sudden death are avoided by employing first a desensitizing injection and then by
      adjusting the doses according to the febrile reaction and by making the highly
      diluted injections slowly. Horses undergoing this process of immunization remain
      in good condition and may even gain in weight. Specific immune bodies appear in
      the serum early and rise rapidly. By inoculating alternately several strains of
      living meningococci and parameningococci, and the autolyzed products of each, a
      polyvalent serum of high titer can be produced in 8 to 12 weeks instead of in the
      10 months required by the subcutaneous method. The serum produced by this rapid
      method has been employed therapeutically in America, England, France, and some
      other countries. It is highly desirable to isolate meningococci from many sources
      and test the strains against the polyvalent serum. Strains which are not
      agglutinated in high dilution in such a serum should be included subsequently in
      the lot of strains used for immunization.

PMID- 19867996
TI  - THE INFLUENCE OF TYPHOID BACILLI ON THE ANTIBODIES OF NORMAL AND IMMUNE RABBITS.
AB  - The subcutaneous, intraperitoneal, or intravenous inoculation of cultures of
      typhoid bacilli did not cause, as far as could be determined, a decrease in the
      antibody content of the blood serum of the rabbit. On the other hand, the
      intravenous inoculation of typhoid bacilli causes a rapid mobilization of normal
      antibodies, thus increasing their concentration in the blood, to be followed
      somewhat later, as in the other forms of inoculation, by the production of so
      called acquired antibodies. No such condition as the negative phase of Wright was
      discovered, although especially looked for in the experiments.

PMID- 19867997
TI  - KLOSSIELLA INFECTION OF THE GUINEA PIG.
AB  - We have found in the kidneys of twelve supposedly normal guinea pigs, coming from
      Pennsylvania and New Jersey, a parasite that closely resembles in some of its
      phases Klossiella muris, described by Smith and Johnson, and the renal parasite
      of two West African guinea pigs, described by Seidelin. The forms most commonly
      found by us and described as the sporoblast cycle, are evidently similar to those
      described by Smith and Johnson and by Seidelin. There are certain discrepancies
      of measurement between the parasite described by Seidelin and the one here
      described, but the most important difference between the two is the different
      number of sporozoites resulting from a final division of the daughter
      sporoblasts. Seidelin has found thirty sporozoites; we have found from eight to
      twelve, while the usual number is eight. Further, we have found a ring form which
      is unlike any of the stages in either the sporoblast or schizogonic cycle, and
      which we interpret tentatively as the male element or microgamete. In addition,
      we have found a tubular form which resembles the glomerular body of Klossiella
      muris and which we think is the schizogonic phase of this parasite.

PMID- 19867998
TI  - CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC : IV. THE CHARACTER AND
      DISTRIBUTION OF RENAL INJURY PRODUCED BY ARSENICALS AS INDICATED BY THE PROCESSES
      OF REPAIR.
AB  - 1. The processes of repair in the kidneys of guinea pigs after sublethal doses of
      certain arsenical compounds indicate that all arsenicals do not produce a purely
      vascular type of renal injury. 2. While some arsenicals produce a predominantly
      vascular injury and others produce a predominantly tubular injury, both these
      tissue elements are undoubtedly always affected, although in varying proportion.
      In addition, the interstitial connective tissue is probably always affected. The
      diffuse proliferation of this tissue may be relatively conspicuous in the
      processes of repair after arsenicals that cause but slight vascular injury. 3.
      All red kidneys do not necessarily show identical pictures during the processes
      of repair; the same is true of pale kidneys. 4. The mode of action of an
      arsenical compound as a renal toxic agent is bound up with the chemical
      constitution of the compound.

PMID- 19867999
TI  - EXPERIMENTS WITH POLIOMYELITIS IN THE RABBIT.
AB  - The poliomyelitic virus obtained from an experimental monkey has been passed
      through eight generations in rabbits. It shows no signs of dying out. On the
      other hand, it gives no evidence of becoming more pathogenic to the species
      through successive passage. The period of incubation remains variable and the
      percentage of takes has not increased. Whether eventually a virus can be obtained
      which is of heightened virulence to rabbits is problematic. All inoculations are
      by no means successful. The animals show great individual differences in
      susceptibility to the virus, as is evidenced by the fact that out of fifty-four
      rabbits inoculated, only twenty-two, or about 40 per cent, succumbed. This fact
      may explain the negative results of other investigators. At several points in the
      series of experiments it was thought that the strain had died out. As many as six
      rabbits have been inoculated one after the other before the virus would catch
      again. The age of the rabbits is important in considering the susceptibility.
      From the limited data at our command, adult rabbits are resistant, and there
      appears to be an abrupt increase in resistance between the age of 6 and 8 weeks;
      that is, rabbits under 6 weeks are more susceptible to the virus. There seems to
      be a parallel between the age incidence of this disease in rabbits and
      spontaneous poliomyelitis in man. The age incidence of poliomyelitis in man is
      indicated by the term "infantile paralysis." Several methods of inoculation have
      proved successful; thus the rabbits have succumbed as a result of introducing the
      virus directly into the brain, by injecting it into a peripheral nerve, or
      directly into the circulation, or by placing it upon the uninjured nasal mucosa.
      The symptoms produced show more or less departure from the symptoms of
      poliomyelitis as seen in the spontaneous disease in man and in the experimental
      disease in the monkey. There are two distinct pictures recognizable. In one there
      is paralysis of one or more of the extremities which progresses until death,
      resembling somewhat the symptoms of the experimental disease in the monkey. This
      we have designated the progressive type. The other group is included in what we
      have called the fulminating type. The symptoms are explosive in character, with
      extreme weakness amounting to prostration, terminating in death in a few hours,
      attendant upon respiratory failure. The mode of inoculation seems to have little
      effect upon the type of symptoms produced. The period of incubation is variable
      and apparently does not depend upon the method of inoculation. The period varied
      from 2 to 41 days, with an average of 12 days. The two extremes both occurred
      after intracranial injection. After intranasal insufflation the incubation period
      was short, being in each case 2 days, followed by symptoms of the fulminating
      type. The placing of the virus into the nose seems to be an effective method, but
      is as uncertain as other routes, as only three out of nine rabbits tested in this
      manner succumbed. The disease produced by this route was particularly virulent.
      The virus shows no tendency to become fixed. The period of incubation is as
      variable in the eighth generation as in the first, and the virus has shown no
      tendency towards increasing virulence through successive passage, in these
      respects differing from the virus of rabies. We have found the virus to be
      filterable. An emulsion of the central nervous matter of a rabbit of the first
      generation passed through a Berkefeld filter, and injected intracerebrally into
      another rabbit, resulted in death, preceded by symptoms of the fulminating type.
      Virus (unfiltered) from this rabbit was transferred successfully to two other
      rabbits. The lesions, while definite and consistent throughout the series, lack
      the distinctive features of the pathologic picture of poliomyelitis in man and
      the monkey. Capillary congestion, punctate hemorrhages, degeneration of the motor
      cells, satellitosis, and more or less cellular infiltration of the gray matter of
      the cord and medulla are found, but perivascular infiltration is absent and the
      infiltrating cells are not lymphocytic in character. One of the most striking
      features of this investigation is the way in which rabbits and monkeys react to
      the same virus. The disease in the rabbit presents certain clinical resemblances
      to the experimental disease in the monkey and also to the spontaneous disease in
      children. On the other hand, the symptoms show marked variation from those seen
      in the monkey and in man. The picture has not the same constancy in rabbits and
      could not in most cases be recognized clinically as poliomyelitis. There are
      still more marked differences in the pathology. While it is true that the brunt
      of the attack in the rabbit falls upon the gray matter of the cord and medulla,
      the appearance of the lesions under the microscope shows such differences from
      the lesions of experimental poliomyelitis in monkeys, as well as the natural
      disease in man, as to suggest two distinct infections. It is more reasonable,
      however, to assume that we are dealing with a modified form of poliomyelitis;
      that the rabbit reacts differently to the virus than the monkey or man; and that
      the disease produced in rabbits by us and others is in fact poliomyelitis. So far
      as we know, no other virus produces such differences in two animal species.
      Smallpox is so profoundly altered in the cow that it took almost 100 years to
      prove Jenner's assumption that cowpox is a modified form of smallpox. However,
      the pock of vaccinia is a correct counterpart both clinically and pathologically
      of the pock of variola. If the virus of poliomyelitis may be so altered in the
      rabbit as scarcely to be recognizable, may it not be still more profoundly
      changed in other animals? The conjecture then arises that poliomyelitis, instead
      of being limited naturally to man and experimentally to monkeys, may in fact
      occur in other animals in unnoticed or unrecognized form. If this should prove
      true, it may be a source of human infection and may help to solve the problem of
      prevention.

PMID- 19868000
TI  - FEEDING EXPERIMENTS WITH BACTERIUM PULLORUM. THE TOXICITY OF INFECTED EGGS.
AB  - The problem of eradicating ovarian infection in the domestic fowl assumes still
      greater importance than heretofore, in the light of data recently acquired. Not
      only is it of great significance to eliminate the permanent carriers of Bacterium
      pullorum from all flocks of fowls from the standpoint of successful poultry
      breeding, but also because they constitute a possible source of danger to man.
      Eggs which harbor Bacterium pullorum in the yolk in large numbers may produce
      abnormal conditions, when fed, not only in young chicks, but in adult fowls,
      young rabbits, guinea pigs, and kittens. The toxicity for young rabbits is most
      pronounced, the infection usually resulting in the death of the animals. In
      kittens the most prominent symptoms are those of severe food-poisoning with
      members of the paratyphoid group of bacteria. The possibility of infected eggs
      causing serious disturbances in young children and in the sick and convalescent
      of all ages must therefore receive serious consideration. Ovarian infection of
      fowls is very common throughout this country. Hence, a large proportion of the
      marketed eggs are infected with Bacterium pullorum. When such eggs are allowed to
      remain in nests under broody hens, or in warm storage places, for comparatively
      few hours, they contain large numbers of the organism. Soft boiling, coddling,
      and frying on one side only do not necessarily render the yolks free from viable
      bacteria; therefore, eggs which have gone through these processes may, like raw
      eggs, be the cause of serious disturbances in persons who are particularly
      susceptible to such influences, and especially to infants. That no well
      authenticated instances of egg-poisoning of this kind are on record does not
      warrant the assumption that there have been no cases. The etiology of infantile
      stomach and intestinal disturbances is as yet too little understood; in fact, it
      may be said that many of these disorders have no known cause, and almost as much
      may be said regarding gastro-intestinal diseases in later life. Furthermore,
      since the ailments caused by infected eggs would not make themselves felt
      presumably until several days after their ingestion, little or no suspicion would
      fall upon the eggs. It may be said, too, that the wide distribution of ovarian
      infection in the domestic fowl has come about only in the last few years, hence
      its possible danger to man is one of recent development.

PMID- 19868001
TI  - SERUM CHANGES AND THE CAUSE OF DEATH IN EXPERIMENTAL PANCREATITIS : STUDIES ON
      FERMENT ACTION. XXX.
AB  - 1. The serum changes observed during acute experimental pancreatitis indicate
      that the shock and death are due to an intoxication from protein split products,
      and not to an intoxication from pure tryptic ferment. 2. When the pancreatitis is
      produced by the injection of an anti-proteolytic substance (sodium oleate), the
      degree of intoxication bears no relation to the degree of tissue destruction. 3.
      The increase in serum antiferment apparently favors the recovery of the animal.

PMID- 19868002
TI  - SERUM CHANGES FOLLOWING THYROPARATHYROIDECTOMY : STUDIES ON FERMENT ACTION. XXXI.
AB  - 1. In thyroparathyroidectomized dogs the onset of tetany bears no constant
      relation to the ferment-antiferment balance of the serum. 2. The serum lipase
      titer remains at a low level throughout. 3. A progressive increase in non
      coagulable nitrogen and proteoses is observed in the serum following the removal
      of the glands. 4. The amino nitrogen of the serum is usually increased at the
      time when tetany is most marked.

PMID- 19868003
TI  - THE DISAPPEARANCE OF DEXTROSE FROM THE BLOOD AFTER INTRAVENOUS INJECTION.
AB  - 1. As has been found by other investigators, when a large amount of dextrose is
      injected intravenously into a normal dog it disappears from the circulating blood
      in about 90 minutes after the end of the injection. Varying amounts (an average
      of 60 per cent) are excreted in the urine. 2. Even in nephrectomized animals the
      same quantity will leave the circulation in the same length of time as in normal
      animals. 3. This phenomenon seems to be, at least to a great extent, independent
      of vital processes, since dextrose, after intravenous injection into dead
      animals, is found to leave the blood rapidly. 4. The phenomenon is independent of
      the important abdominal organs, for it also occurs in animals (living or dead) in
      which the aorta and inferior vena cava have been ligated near the diaphragm, thus
      abolishing most of the circulation posterior to the diaphragm. 5. The fact that a
      considerable amount of the sugar passes from the circulation into the surrounding
      tissues was established by finding an increase in the carbohydrates of the muscle
      tissue. This was done in the case of the living anterior animals and in the whole
      and anterior dead animals. In most of these experiments there was also evidence
      of the formation of polysaccharides in the muscle tissue.

PMID- 19868004
TI  - THE FUNCTION OF THE KIDNEY WHEN DEPRIVED OF ITS NERVES.
AB  - 1. By means of vascular suture it is possible to remove the dog's kidney from the
      body and later to restore it to its former position. 2. Such a kidney is removed
      from the control of the nervous system, at least for a time. 3. Examination of
      the function of a kidney so treated shows an initial period of overaction, as
      compared with that of the normal kidney. 4. This is followed by balanced action.
      5. The more recent tests of renal function show that a single, reimplanted kidney
      is able to maintain normal life indefinitely. 6. The results of these
      experiments, together with the evidence already at hand, suggest strongly that
      secretory nerves to the kidney do not exist.

PMID- 19868005
TI  - A METHOD FOR OBTAINING SUSPENSIONS OF LIVING CELLS FROM THE FIXED TISSUES, AND
      FOR THE PLATING OUT OF INDIVIDUAL CELLS.
AB  - Individual, living, tissue cells can be obtained in suspension by digesting with
      trypsin the clot of growing tissue cultures. Under these circumstances the living
      cells assume a spherical form. When washed and plated in fresh plasma they put
      out processes and proliferate. After growth in the new plates has occurred the
      digestion and plating can be repeated. The limits of the method have not yet been
      reached. We are at work on a number of the problems which it has opened up.

PMID- 19868006
TI  - THE PURE CULTIVATION OF SPIROCHAETA ICTEROHAEMORRHAGIAE (INADA).
AB  - Pure cultures of the spirochaetal causative agent of the disease known as Weil's
      disease, or febrile icterus, in Japan, have been obtained by us in a solid, a
      semisolid, and a fluid medium. The spirochaeta thus isolated remains pathogenic
      for guinea pigs for many generations. Up to the present time we have succeeded
      through the courtesy of Professor Nagayo, Dr. Konuma, and Dr. Ishihara, in
      cultivating three different strains. The spirochaeta is a facultative anaerobe.
      The solid and semisolid culture media possess one disadvantage, in that they are
      opaque on account of the addition of red blood corpuscles; but it is hoped that
      this drawback may soon be overcome by further studies. We shall report later the
      results of investigations regarding various questions in immunity as well as
      further details regarding the biological properties of the spirochaeta.

PMID- 19868007
TI  - THE BACTERICIDAL PROPERTIES OF THE QUATERNARY SALTS OF HEXAMETHYLENETETRAMINE :
      I. THE PROBLEM OF THE CHEMOTHERAPY OF EXPERIMENTAL BACTERIAL INFECTIONS.

PMID- 19868008
TI  - THE BACTERICIDAL PROPERTIES OF THE QUATERNARY SALTS OF HEXAMETHYLENETETRAMINE :
      II. THE RELATION BETWEEN CONSTITUTION AND BACTERICIDAL ACTION IN THE SUBSTITUTED
      BENZYLHEXAMETHYLENETETRAMINIUM SALTS.
AB  - By the addition of substituted benzyl halides to hexamethylenetetramine, a series
      of quaternary salts of this base was obtained. These salts represent a new group
      of organic bactericides. The results obtained in the tests with these substances
      upon Bacillus typhosus have demonstrated the existence of direct relationships
      between chemical constitution and bactericidal action within the series. The
      bactericidal character is directly attributable to the presence of the
      hexamethylenetetramine nucleus. The degree of the bactericidal action, however,
      is determined by the position, character, and number of the groups substituted in
      the benzene nucleus. By the introduction of the methyl, chlorine, bromine,
      iodine, cyano, and nitro groups into the benzene nucleus of the parent benzyl
      hexamethylenetetraminium salt, the bactericidal power of this compound was
      notably enhanced. The substitution of these groups in the ortho position almost
      invariably resulted in substances which were more active than their meta or para
      isomers. The introduction of the methoxy group was without marked effect. Several
      substances in which two hexamethylenetetraminium side-chains occurred were found
      to be the most active of the substances of this series when tested against
      Bacillus typhosus. Comparative tests with other bacterial types demonstrated that
      these compounds possessed a marked degree of specificity for Bacillus typhosus.

PMID- 19868009
TI  - THE BACTERICIDAL PROPERTIES OF THE QUATERNARY SALTS OF HEXAMETHYLENETETRAMINE :
      III. THE RELATION BETWEEN CONSTITUTION AND BACTERICIDAL ACTION IN THE QUATERNARY
      SALTS OBTAINED FROM HALOGENACETYL COMPOUNDS.
AB  - The extension of the study of the quaternary salts of hexamethylenetetramine to
      those obtained by the addition of this base to the most varied types of
      substances containing aliphatically bound halogen has demonstrated that the
      introduction of the hexamethylenetetramine nucleus in this manner results in the
      production of bactericidal substances or enhances the bactericidal action if
      already present. In particular it was found possible by the use of the
      halogenacetyl group, XCH(2)CO, as a connecting link, to furnish primary and
      secondary aliphatic and aromatic amines, alcohols, and hydrocarbons of the most
      varied character with the hexamethylenetetramine molecule and to study the
      relation between chemical constitution and bactericidal action in the series of
      substances so prepared. Because of the variety of chemical types studied, the
      results are too involved for a detailed summary here. Many of the substances were
      found to be very powerful bactericides, and in a number of instances derivatives
      of purely aliphatic nature were found to possess an unusual bactericidal power.
      Bacillus typhosus, streptococcus, meningococcus, and gonococcus were the
      microorganisms used for the tests, and striking instances of partial specificity
      were observed. This specificity was found to favor not one species alone, but
      instances were found in which each of the types of bacilli was shown to be
      especially susceptible to one or another of the particular types of compound
      employed. The source of this partial specificity is to be sought not in the
      hexamethylenetetramine nucleus itself but in the molecule to which it is
      attached. The action of some of the substances was tested in the presence of
      serum or protein and was found to be not at all or only slightly inhibited. In
      other cases marked inhibition occurred. The factors controlling the serum- or
      protein-compatibility of these substances are likewise to be sought in that
      portion of the molecule other than the hexamethylenetetramine.

PMID- 19868010
TI  - THE PROTECTION OF PATHOGENIC MICROORGANISMS BY LIVING TISSUE CELLS.
AB  - 1. Living phagocytes are able to protect ingested organisms from the action of
      destructive substances in the surrounding fluid, and even from a strong
      homologous antiserum. 2. There is evidence that the protection by phagocytes is
      largely if not entirely conditioned on their being alive. 3. These facts should
      be taken into consideration in the study of diseases caused by infectious agents
      capable of living within tissue cells.

PMID- 19868011
TI  - THE EFFECT OF DIGITALIS ON THE NORMAL HUMAN ELECTROCARDIOGRAM, WITH ESPECIAL
      REFERENCE TO A-V CONDUCTION.
AB  - Digitalis was given by mouth to five normal young male adults in amounts ranging
      from 2.0 to 3.0 gm. of standardized leaves in the course of 7 to 10 days. The As
      Vs interval was prolonged in four of the five subjects, the greatest prolongation
      occurring in the case of the subject who received the most digitalis and none at
      all in one who received only 2.0 gm. There was no prolongation to so great an
      interval as 0.2 second until 2.7 gm. had been taken. The effects of the digitalis
      on conduction time began 5 to 6 days after the drug had been started and after
      1.5 to 1.8 gm. had been taken. The effects persisted for 1 to 2 weeks after the
      drug had been stopped. Atropine removed completely the effect of digitalis on A-V
      conduction. The slowing heart rate after exercise was accompanied by an
      enhancement of the defect in conduction. The change in conduction through
      digitalis was therefore almost entirely, if not entirely, due to increase of
      vagal tone and irritability. Digitalis did not affect to an appreciable extent
      the Q-end of S and the Q-end of T intervals. Exercise and atropine both shortened
      the ventricular complex Q-end of T while the subject was under digitalis. The
      amplitude of the T wave, especially in Lead II, was changed within 48 hours after
      digitalis had been started, a decrease then beginning which became greater as the
      drug was continued and which persisted until 10 to 19 days after the digitalis
      had been stopped. The change in the T deflection preceded by several days the
      change in conduction time. The T wave, therefore, in the normal subject as well
      as in the patient gives us the earliest indication of digitalis action. The
      amplitudes of P, Q, R, and S were not materially influenced by the amounts of
      digitalis given. The pulse rate in two subjects became lower than usual at night
      as the result of the digitalis; otherwise there was no evidence of vagal action
      on the sino-auricular node. Blood pressure was uninfluenced by the digitalis.
      Mild subjective sensations occurred in all the subjects during the administration
      of the drug. A curious, hitherto undescribed, digitalis arrhythmia consisting of
      blocked auricular premature beats occurred in one subject after 3.0 gm. of
      digitalis had been taken.

PMID- 19868012
TI  - THE INFLUENCE OF TETHELIN, AND OF OTHER ALCOHOL-SOLUBLE EXTRACTIVES FROM THE
      ANTERIOR LOBE OF THE PITUITARY BODY, UPON THE GROWTH OF CARCINOMATA IN RATS.
AB  - 1. The hypodermic administration of tethelin increases markedly the rate of
      growth of the primary tumor and the tendency to form metastases in rats
      inoculated with carcinoma, in this, as in other respects, reproducing the action
      of the whole anterior lobe of the pituitary body. 2. Other alcohol-soluble
      extractives of the anterior lobe of the pituitary body, with the exception of the
      lecithin fraction, exert no appreciable effect upon the growth of carcinomata in
      rats. 3. The lecithin fraction, as in previously reported experiments in which we
      employed lecithin obtained from eggs, causes evident retardation of the growth of
      carcinomata in rats.

PMID- 19868013
TI  - THE INTRAVENOUS INJECTION OF MAGNESIUM SULPHATE FOR ANESTHESIA IN ANIMALS.
AB  - These experiments justify the following general conclusions. By the intravenous
      injection of M/4 magnesium sulphate into dogs at a certain rate, a stage can be
      reached where the abdominal walls are completely relaxed and when section of the
      abdomen and stimulation of sensitive parts of the parietal peritoneum do not
      produce pain or elicit any reaction of the animal. At the same time spontaneous
      respiration may still be maintained within normal limits and the lid reflex be
      fair or even normal. In this stage intratracheal intubation for artificial
      respiration can be easily accomplished. This stage may be attained in 12 to 14
      minutes when the rate of injection is about 3 cc. per minute. When this stage is
      once attained the rate of injection should gradually be reduced, otherwise,
      sooner or later, spontaneous respiration will be abolished, and by a further
      maintenance of the rate of injection all the skeletal muscles may become
      paralyzed. When the injection of magnesium is continued for a longer period, the
      paralytic effects of the magnesium injection will set in, even when administered
      at a slow rate. The paralysis of the respiratory function is readily met by
      intrapharyngeal insufflation, which is easily executed even without training in
      this procedure, or by the method of intratracheal insufflation, if executed by
      one trained in its management. When the respiration of the animal is accomplished
      by insufflation, the paralytic effect of the magnesium may be abolished fairly
      rapidly by an intravenous injection of about 10 cc. of an M/8 calcium chloride
      solution; or it may disappear slowly, after the infusion of the magnesium
      solution is discontinued for some time. The latter mode of disappearance may be
      favorably accelerated by an intravenous infusion of 60 to 100 cc. of an M/4
      solution of sodium sulphate. The production of anesthesia by intravenous
      injection of magnesium sulphate should not be undertaken unless an apparatus for
      intrapharyngeal insufflation is at hand, because in exceptional cases the
      disappearance of spontaneous respiration may be one of the earliest consequences
      of the magnesium injection. The injection of calcium chloride should not be
      employed in cases in which the subject shows cardiac insufficiency. In such
      instances, moreover, injections of magnesium should not be used for the purpose
      of anesthesia; at least not until greater experience has been acquired in the
      employment of this method.

PMID- 19868014
TI  - AN EXPERIMENTAL STUDY OF THE ADDITIVE AND ANTAGONISTIC ACTIONS OF SODIUM OXALATE,
      AND SALTS OF MAGNESIUM AND CALCIUM IN THE RABBIT.
AB  - The foregoing experiments establish firmly the following facts. Subcutaneous or
      intramuscular injections of sodium oxalate in subtoxic doses, when administered
      to an animal which received a subminimal dose of magnesium sulphate, produce
      profound anesthesia and paralysis of long duration, although the usual effects of
      sodium oxalate alone are of a stimulating character. This fact is, in general, in
      harmony with the results reported by Starkenstein who, however, seems to have
      used the combination of the two salts in one solution; namely, that of magnesium
      oxalate. The combined injections of subminimal doses of sodium oxalate and
      magnesium sulphate produce a strong reduction, or even, at times, a complete
      abolition of the conductivity of the motor nerve endings. An intravenous
      injection of calcium salts brings on a recovery from the profound and prolonged
      effects of the combined action of sodium oxalate and magnesium sulphate, which is
      as prompt as is observed in experiments in which effective doses of magnesium
      alone were given. This fact is the more noteworthy, since depressions of long
      duration produced by prolonged continuous injections of magnesium solutions alone
      do not respond very promptly and effectively to calcium injections. As will be
      recalled, the starting point for our investigation was the hypothesis that
      substances which are capable of precipitating calcium-a biological antagonist of
      magnesium-ought to be capable of increasing the depressive effect of magnesium.
      Our experiments proved that this assumption was correct. This would seem,
      therefore, to justify the interpretation that the augmenting action of sodium
      oxalate has its cause in the ability of the latter to precipitate calcium and
      thus increase within the body the amount of unantagonized magnesium. However, we
      wish to state expressly that this view is, for the present, still no more than a
      hypothesis and does not exclude other possible interpretations of our facts. As
      we pointed out it speaks against this hypothesis that oxalates do not produce
      phenomena of depression; the toxic symptoms produced by oxalates exhibit
      distinctly signs of increased and not of decreased irritability.

PMID- 19868015
TI  - THE DISTRIBUTION OF TRYPAN-RED TO THE TISSUES AND VESSELS OF THE EYE AS
      INFLUENCED BY CONGESTION AND EARLY INFLAMMATION.
AB  - In as far as the observations reported have a bearing on the movements of fluid
      within the eye, they are, for the most part, in accord with views at present
      generally accepted. On the other hand, we know of no other way in which it may be
      so readily demonstrated that simple and even temporary local circulatory changes
      may profoundly alter the distribution of substances from the circulating blood to
      the extravascular fluids and tissues. In the light of these observations, it
      would seem that such changes might easily account for marked idiosyncrasies in
      the action of poisonous drugs, and as well probably for other factors in drug
      action.

PMID- 19868016
TI  - THE APPEARANCE OF THE PRESSOR SUBSTANCE IN THE FETAL HYPOPHYSIS.
AB  - The pressor substance of the hypophysis is so marked in the pig fetus measuring
      175 mm. that it seems probable that a fetus of this length is independent of the
      secretion of the mother's hypophysis.

PMID- 19868017
TI  - CHEMICAL VERSUS SERUM TREATMENT OF EPIDEMIC MENINGITIS.
AB  - Claims of efficiency have been made at two widely separated periods for the
      chemical treatment of epidemic meningitis, in the first instance for lysol and in
      the second for protargol. The use of lysol was long since abandoned; the
      recommendation for protargol is based on a single series of cases, small in
      number. Because of the variable severity of epidemics of meningitis, small
      reliance can be placed on results of treatment limited in extent to small numbers
      of cases and to one locality. A more uniform and accurate measure of the value of
      a method of treatment is provided by animals infected experimentally with
      pathogenic cultures of meningococci. Young guinea pigs respond in a definite
      manner to intraperitoneal inoculation of virulent meningococci. Neither protargol
      nor lysol proved to have any curative action on the experimental infection thus
      produced in these animals. Monkeys respond in a characteristic manner to the
      inoculation of virulent cultures into the subarachnoid space. Protargol displayed
      no curative action on the experimental infection thus produced in these animals.
      On the contrary, both lysol and protargol exert antileukotactic and
      antiphagocytic effects, and are also potent protoplasmic poisons, and the
      leukocytes with which they come in contact are injured and made to degenerate.
      According to the extent to which these harmful properties are exerted, the
      chemicals promote the advance rather than restrain the progress of meningococcic
      infection. Recovery from meningococcic infection in man and animals is
      accomplished chiefly through the process of phagocytosis. The specific antiserum
      acts curatively by increasing the emigration of leukocytes, by promoting
      phagocytosis directly, and by agglutinating the meningococci, and also by
      neutralizing endotoxin. Any means which interfere with and reduce these essential
      processes retard or prevent recovery. Both lysol and protargol interfere with and
      diminish the emigration of leukocytes and the phagocytosis of meningococci, and
      neither possesses antitoxic power. The mixture of antiserum with lysol and with
      protargol reduces to a certain extent the antileukotactic and antiphagocytic
      effect of the chemicals; but this action is insufficient to set aside wholly the
      injurious effects which they produce. It follows, therefore, that whatever
      theoretical advantages might accrue from a bactericidal activity exerted by these
      chemicals independently of the type of meningococcus causing epidemic meningitis,
      is more than offset by the harmful effects which they cause. Hence specific
      antiserum seems to provide the logical therapeutic agent with which to combat
      epidemic meningitis, since it is itself innocuous and promotes those processes
      essential to recovery from the disease. The problem up to the present has been
      that of producing an antiserum which represents the several types of the
      meningococcus, and this problem is now in a fair way to being solved.

PMID- 19868018
TI  - EXPERIMENTS ON THE DEVELOPMENT OF MALARIA PARASITES IN THREE AMERICAN SPECIES OF
      ANOPHELES.
AB  - Since a knowledge of the susceptibility of any species of Anopheles to infection
      with malaria parasites is of great importance in determining its part in the
      transmission of malaria, the experiments reported here were undertaken, and
      included the three most prevalent species of this genus occurring in the United
      States. As a result of these experiments Anopheles punctipennis is shown to be an
      efficient host of the organisms of tertian and estivo-autumnal malaria, Anopheles
      crucians of estivo-autumnal malaria, at least, and information has been obtained
      upon the relative susceptibility of these two species and Anopheles
      quadrimaculatus. The latter species has been known to be an efficient host since
      Thayer's experiments in 1900, and has been considered to be the principal species
      concerned in the transmission of malaria in the United States. With Anopheles
      punctipennis, developmental forms of the exogenous or sporogenic cycle of
      Plasmodium vivax were demonstrated in six (85 per cent) of the seven mosquitoes
      dissected, and the development of Plasmodium falciparum, in four (20 per cent) of
      twenty specimens. These four infections, however, occurred in a series of
      thirteen specimens fed on one person, so that the percentage was actually 33.
      With Anopheles crucians, oocysts or sporozoites or both oocysts and sporozoites
      of Plasmodium falciparum were found in nine (75 per cent) of the twelve specimens
      dissected. No tests were made with this species and Plasmodium vivax. Anopheles
      quadrimaculatus was employed as a control species in the experiments and became
      infected in the following ratio: eight (66 per cent) of twelve specimens with
      Plasmodium vivax, and three (15 per cent) of nineteen specimens with Plasmodium
      falciparum. In determining the relative susceptibility of the three species only
      those individuals which had fed upon the same gamete carriers are considered. The
      number of mosquitoes from which the percentages are computed is too small to make
      the results entirely conclusive, but the indications are that Anopheles
      punctipennis and Anopheles quadrimaculatus are equally susceptible to infection
      with Plasmodium vivax, 85 per cent of each species under the same conditions
      being positive. With Plasmodium falciparum,Anopheles crucians showed the highest
      percentage of infection (75 per cent), Anopheles punctipennis second (33 per
      cent), and Anopheles quadrimaculatus third (23 per cent).

PMID- 19868019
TI  - INTESTINAL OBSTRUCTION : VI. A STUDY OF NON-COAGULABLE NITROGEN OF THE BLOOD.
AB  - Intestinal obstruction, as a rule, is associated with an increasing amount of non
      coagulable nitrogen in the blood. With acute intoxication the rise in non
      coagulable nitrogen may be rapid and reach as high as three or even ten times
      normal. With more chronic intoxication there may be little or no rise in the
      blood non-coagulable nitrogen. Closed intestinal loops show exactly the same
      picture, and, when combined with obstruction, may give very high nitrogen
      readings. Acute proteose intoxication due to injection of a pure proteose will
      show a prompt rise in blood non-coagulable nitrogen, even an increase of 100 per
      cent within 3 or 4 hours. These intoxications also show a high blood content of
      creatinine and urea. The residual or undetermined nitrogen may be very high. A
      human case of intestinal obstruction with autopsy presents blood findings exactly
      similar to those observed in many animal experiments. Clinically the non
      coagulable nitrogen of the blood may give information of value in intestinal
      obstruction. A high reading means a grave intoxication, but a low reading may be
      observed in some fatal cases and gives no assurance that a fatal intoxication may
      not supervene. The kidneys in practically all these experiments are normal in all
      respects. It is possible that protein or tissue destruction rather than impaired
      eliminative function is responsible for the rise in non-coagulable nitrogen of
      the blood in these acute intoxications. Transfusions of dextrose solutions often
      benefit intestinal obstruction, and may depress the level of the non-coagulable
      nitrogen in the blood. Some cases show no change in non-coagulable nitrogen
      following transfusions and diuresis, and, as a rule, such cases present the most
      severe intoxication.

PMID- 19868020
TI  - THE ORIGIN AND STRUCTURE OF A FIBROUS TISSUE FORMED IN WOUND HEALING.
AB  - 1. In experimental wounds, made by removing various sized pieces of skin from the
      frog, there is a rapid coagulation of the blood plasma and lymph to form a
      coagulation tissue which fills the wound cavity. 2. The observations on the
      living animals show that the coagulation a grave intoxication, but a low reading
      may be observed in some fatal cases and gives no assurance that a fatal
      intoxication may not supervene. The kidneys in practically all these experiments
      are normal in all respects. It is possible that protein or tissue destruction
      rather than impaired eliminative function is responsible for the rise in non
      coagulable nitrogen of the blood in these acute intoxications. Transfusions of
      dextrose solutions often benefit intestinal obstruction, and may depress the
      level of the non-coagulable nitrogen in the blood. Some cases show no change in
      non-coagulable nitrogen following transfusions and diuresis, and, as a rule, such
      cases present the most severe intoxication.

PMID- 19868021
TI  - THE ABSORPTION OF ADRENALIN AFTER INTRATRACHEAL INJECTION.
AB  - In the preceding pages we have submitted evidence which shows that a simple
      intratracheal injection of a solution in a normally breathing rabbit penetrates
      within a few seconds to the alveoli, chiefly those of the left lower lobe; that
      absorption is rapid and well maintained; and that the procedure may be repeated
      effectively a number of times even with a substance like adrenalin which
      decreases absorption. It was also shown that absorption of adrenalin from the
      lung could be obtained at a time when double the dose given intramuscularly
      exerted no blood pressure effect whatever, and that absorption could still take
      place after the development of pulmonary edema, when there was an undoubted
      dilution of the injected solution with a serum-containing liquid and when a
      diminution of the absorptive field had occurred. The solution injected, after
      reaching the alveoli, is probably largely taken up by the capillaries of the
      pulmonary veins. This is indicated by the great rapidity with which an
      intratracheal injection of adrenalin may cause a rise of blood pressure. In
      numerous instances, for example, the pressure began to rise less than 5 seconds
      after the completion of an injection, equaling and even surpassing in rapidity of
      effect an intramuscular injection. Absorption by the lymphatics probably plays a
      secondary part, an assumption rendered all themore likely if we consider that
      lymph nodes are interpolated in the lymphatic pulmonary path, where the bed of
      the lymph stream becomes greatly widened and the current slowed. Injection into
      the lungs, however, offers another advantage due to the vascular arrangement of
      the absorbing field which could be of value therapeutically. Absorption of
      liquids injected into the lung probably takes place largely through the
      capillaries of the pulmonary veins; to a slight extent possibly through the
      capillaries of the bronchial veins which empty partly into the pulmonary veins,
      partly into the azygos veins; and probably some absorption occurs also through
      the lymphatics. By far the larger proportion of the absorbed material will thus
      be rapidly delivered to the left auricle and then to the left ventricle. At each
      succeeding systole, as long as absorption continues, a fraction of the drug will
      be driven into the coronary arteries and be able to affect the musculature of the
      cardiac pump. This fact ought to render the procedure of intratracheal injection
      a valuable method when it becomes imperative to stimulate a suddenly failing
      heart as promptly as possible by drugs of the digitalis group. Intratracheal
      injection is perhaps better under the conditions mentioned than the intravenous
      route, for the surface veins cannot always be entered with promptness and
      certainty even under fairly normal conditions, and in cases of cardiac weakness
      the difficulties will be measurably increased, while an intratracheal injection
      can be carried out with ease. Moreover, it is legitimate to expect that some
      absorption will take place from the lung alveoli as long as the heart-lung
      circulation persists, no matter how feebly, and that thus some of the drug will
      reach the heart to act on this structure itself more promptly perhaps than when
      the drug is administered successfully through surface veins. As far as the
      intramuscular route is concerned, we have shown that the intratracheal injection
      of adrenalin gives prompt though diminished absorption at a time when double the
      dose intramuscularly exerts no blood pressure effect whatever. The technical
      difficulties of giving an intratracheal injection in animals are slight.
      Tracheotomy as practised by us in the present series of experiments is not
      necessary, for the injection may be given into the intact trachea without
      exposure of the trachea. The hypodermic needle is inserted through the skin about
      1 cm. below the larynx in a slanting caudad direction; the entrance of the needle
      into the trachea is readily felt. The injection should not be so rapid that the
      injected solution fills the entire tracheal lumen, but it should flow down the
      sides of the trachea. If the lumen is entirely filled, an expiration may drive
      some of the injected liquid into the larynx causing cough. In our experiments
      each injection of about 0.5 cc. consumed approximately 5 seconds. In the human
      subject no data are available as far as our knowledge goes, but a priori it would
      seem that an intratracheal injection is almost as simple as in the lower animals.
      The free hypodermic needle could be inserted into the tracheal lumen immediately
      below the cricoid cartilage. The needle itself should preferably be connected
      with the syringe by a short length of rubber tubing to minimize the danger of
      breaking the needle by a sudden move of the patient. The amount of the solution
      should not be too small, so that at least a fraction of it may reach the alveoli
      as promptly as possible; 3 to 5 cc. probably would suffice. Insertion of the
      needle in the locality mentioned would puncture the isthmus of the thyroid, but
      this is of no significance, especially when the procedure is employed in cases of
      cardiac failure where the gravity of the condition would warrant incurring much
      heavier risks than a slight bleeding from the thyroidal isthmus. In conclusion it
      may be said that the incorporation of drugs by intratracheal injection, while not
      as generally applicable as other methods, nevertheless has advantages which
      warrant its use also in human therapeutics.

PMID- 19868022
TI  - THE PRODUCTION OF AMYLOID DISEASE AND CHRONIC NEPHRITIS IN RABBITS BY REPEATED
      INTRAVENOUS INJECTIONS OF LIVING COLON BACILLI.
AB  - The repeated intravenous injection of rabbits with living Bacillus coli communior
      over long periods has resulted in the formation of amyloid deposits in the
      spleen, liver, and kidneys. Suppurative lesions were not present in most cases
      and therefore not a factor in its production. The results have been constant in
      that amyloid was found in all rabbits, eight in number, which were injected over
      a period of 88 days or more. Eight rabbits showed amyloid in the spleen, six of
      these in the kidneys also, and three in the liver. The kidneys of these eight
      rabbits also showed as a result of the injections a subacute and chronic
      glomerulitis, parenchymatous degeneration, some interstitial infiltration with
      round cells, and a slight cellular proliferation of connective tissue, thus
      resembling the chronic parenchymatous nephritis of man which is so commonly
      associated with amyloid disease.

PMID- 19868023
TI  - BACTERIOLOGICAL AND EXPERIMENTAL STUDIES ON GASTRIC ULCER.
AB  - It must be assumed that some cause is operative in certain cases preventing the
      healing of defects in the gastric mucosa and is inoperative in others. Even
      though anhemolytic streptococci are present in practically all gastric ulcers, we
      cannot convince ourselves that these organisms have been proven as yet to be the
      factor which either initiates the ulceration or prevents healing. Nevertheless,
      the constant presence of streptococci in this type of lesion is a suggestive fact
      and further experiments to determine their significance are being undertaken.

PMID- 19868024
TI  - THE EFFECT OF ADULT CHICKEN ORGAN GRAFTS ON THE CHICK EMBRYO.
AB  - The explanation of the wide-spread changes in the embryo after grafting with
      adult organs offers a problem of considerable interest. Just what factors are
      responsible for them we are unprepared to say. They occur only after the grafting
      of certain adult homologous organs and are absent after grafting with such
      tissues as the chicken sarcoma, adult muscles, bone, and cartilage. Likewise no
      systemic changes have been observed after grafting of various tissues from
      foreign species, such as rat and mouse embryos, rat and mouse tumors of various
      sorts, or the normal organs of an adult animal of a foreign species. Whether or
      not this extensive proliferation of the white blood cell elements is to be looked
      on as a stimulation of a center with metastasis in the membranes and organs, or
      whether it is a general stimulation to the anlage of the various cells, is a
      point difficult to determine. Judging from the distribution and character of the
      proliferation, the latter seems the more plausible view. Moreover, the reaction
      may be of the same type as that observed by Da Fano in mice after immunization
      against cancer by means of tissue injections. The changes he describes, however,
      were not so pronounced in character and were for the most part confined to the
      plasma cell in the connective tissues. The possibility of the action of infection
      must also be considered. Smears from the embryo spleen and the scattered nodules
      failed, however, to show microorganisms, and cultures taken on the ordinary media
      were negative for bacteria. If the reaction was a result of bacterial invasion,
      we should expect to find the changes occurring after the implantation of some of
      the transplantable rat and mouse tumors, for it is well known that they become
      highly contaminated. But such is not the case. A possible explanation of the
      necrosis is that the nutrition supply does not keep pace with the growth, so that
      a condition develops analogous to that of the central necrosis in rapidly growing
      tumors. We conclude, therefore, that grafts of adult spleen, bone marrow, liver,
      and kidney placed in the outer membrane of a chick embryo cause stimulation of
      the embryo spleen and lead to proliferation of certain leukocytic elements in the
      mesoderm, subcutaneous tissues, and around vessels in the liver and kidney.

PMID- 19868025
TI  - FURTHER OBSERVATIONS ON THE AGGLUTINATION OF BACTERIA IN VIVO.
AB  - 1. Pneumococci, dysentery bacilli of the Shiga type, and Bacillus mucosus
      capsulatus are agglutinated immediately when injected into the circulation of
      actively immunized rabbits. 2. Staphylococcus aureus and albus, colon bacilli,
      meningococci, gonococci, and non-virulent pneumococci agglutinate in the
      circulation of normal rabbits. 3. Bouillon cultures of Bacillus avisepticus are
      highly toxic for both rabbits and dogs. The fresh sera of these animals have no
      bactericidal action upon the bacteria. Dog serum opsonized the bacilli in vitro,
      and they are agglutinated and opsonized in the circulation and organs of normal
      dogs. On the other hand, none of this occurs in connection with normal rabbits. A
      very small quantity of culture produces a fatal septicemia in rabbits, but a
      subtoxic dose is without effect in dogs. 4. The degree of agglutination and
      opsonization of bacteria within the animal body is inversely parallel to the
      infectiousness of the bacteria for the host.

PMID- 19868026
TI  - THE AGGLUTINABILITY OF BLOOD AND AGAR STRAINS OF TYPHOID BACILLI.
AB  - Cultivation on 10 per cent rabbit blood agar did not affect the agglutinability
      of fifty-seven strains of typhoid bacilli. The authors were unable to confirm the
      observations of Gay and Claypole on the variation in agglutinability caused by
      cultivating the typhoid bacillus on blood agar. A typhoid bacillus showing
      irregularity in fermentation, agglutination, and indol production is described.

PMID- 19868027
TI  - A FINAL REPORT ON THE CULTIVATION OF THE TUBERCLE BACILLUS FROM THE SPUTUM BY THE
      METHOD OF PETROFF.
AB  - In summing up the practicability of the Petroff method which is in reality a
      refinement and improvement upon well known methods, it has possibilities both
      from the standpoint of diagnosis and the study of the tubercle bacillus. It is
      not a difficult technique, but requires considerable attention to detail. The
      results should be better in larger series of cases carried on in laboratories
      where more time is available for close observation of the cultures during the
      early periods of development. It is the early transplanting of minute colonies
      even in the presence of contaminations which results in pure cultures. As to the
      practical value of the method, my experience would lead me to conclude that where
      sputum is obtainable in suspected cases of tuberculosis in which the tubercle
      bacillus cannot be demonstrated, an opportunity for diagnosis would be missed if
      this technique were not applied. If the result is negative it means nothing; if
      positive an otherwise obscure case may be cleared up. The Petroff method offers
      an easy opportunity of isolating large numbers of pure cultures (Table I).

PMID- 19868028
TI  - VARIATIONS IN THE PNEUMOCOCCUS INDUCED BY GROWTH IN IMMUNE SERUM.
AB  - 1. The growth of virulent pneumococci in homologous immune serum produces (a)
      variations in agglutinability, (b) decrease in virulence, (c) inhibition of
      capsule formation, (d) increase in phagocytability with normal serum, and (e)
      change in absorption power and antigenic properties. 2. Reversion to the original
      type in these changed forms takes place upon animal passage.

PMID- 19868029
TI  - THE CONDITIONS AND CHARACTERS OF THE IMMUNITY PRODUCED IN THE GUINEA PIG BY
      INSTILLATION OF HORSE SERUM INTO THE NOSE.
AB  - 1. Normal guinea pigs treated by four to six instillations of horse serum into
      the nose on alternate days become either hypersensitive or refractory to an
      intravenous injection of 0.38 cc. of serum given 16 days after the last
      instillation. If the amount of serum in each instillation is as much as 0.2 cc.,
      anaphylactic death is caused by the toxic injection. If the amount of serum in
      each instillation is reduced to 0.04 cc. the first intravenous injection is
      without marked effect, and a second injection and subsequent injections of the
      same amount of antigen are well tolerated in about half the cases. 2. The effect
      produced by a given dose of serum, whether protective or anaphylactic, depends
      probably upon the extent of contact with the mucous membrane of the nose. 3.
      Guinea pigs which, after nasal treatment, have become tolerant to a definite
      maximum intravenous injection of the antigen appear to increase the degree of
      their tolerance, at least up to a resting period of more than 4 months. The same
      does not hold in animals immunized by the peritoneal route. 4. The first two or
      three instillations of a series probably determine the biologic character,
      whether of hypersensitiveness or hyposensitiveness, of reaction towards the
      serum. 5. It is probable that, contrary to the case in parenteral sensitization,
      hypersensitiveness and protection, respectively, set up by nasal instillations
      and not followed by parenteral injections, gradually disappear in about 50 to 100
      days. 6. We have failed in attempts to eliminate hypersensitiveness, due to
      subcutaneous injection of serum, by nasal instillations which would protect the
      normal animal from the development of anaphylaxis. 7. It is suggested that the
      principles of prophylaxis evolved under these relatively simple conditions should
      be applied in the study of infectious disease.

PMID- 19868030
TI  - IMMUNITY FACTORS IN PNEUMOCOCCUS INFECTION IN THE DOG.
AB  - Intravenous inoculations of from 1 to 3 cc. per kilo of body weight of a bouillon
      culture of virulent pneumococci produce septicemia and meningitis in dogs. The
      injected pneumococci leave the circulation rapidly, but begin to reinvade the
      blood from 24 to 48 hours later. The septicemia reaches its climax between the
      4th and 5th days and then abruptly declines, the blood becoming sterile within
      from 1 to 3 days after the height of the septicemia is reached. The initial
      disappearance of the pneumococci from the circulation has been found to be due to
      agglutination of the diplococci in the blood stream and accumulation of the
      clumps in the lungs, liver, spleen, etc. If the dogs are reinoculated during the
      ascension of the septicemia, the injected diplococci leave the circulation as
      rapidly as in normal dogs. Cultures isolated in this stage of the infection, both
      before and from 3 to 4 hours after the reinoculation, are resistant to the
      agglutinins and opsonins of immune sera that agglutinate and opsonize the
      cultures with which the dogs were originally infected. Thus it follows that the
      pneumococci are able to reinvade the circulation because they have acquired a
      fastness to the existing antibodies and not because the antibodies have been
      bound or exhausted. By reinoculating dogs at the time of the crisis in the
      septicemia it has been shown that the agglutination of the pneumococci is more
      rapid and complete and that the diplococci leave the circulation much more
      rapidly than in normal dogs. Hence acquired antibodies are operative within the
      animals at this time although they cannot be demonstrated in vitro until from 24
      to 48 hours later. Pneumococci isolated as the infection is subsiding are more
      susceptible to the action of immune sera than the original cultures injected. It
      is probable that all the dogs would have survived the infection if a meningitis
      had not developed. In the acutely fatal cases of meningitis few pneumococci are
      phagocyted, while in the milder and convalescent cases much phagocytosis occurs.
      It is suggested that the incubation period of infectious diseases is due to the
      fact that the infecting agents must become adapted to the adverse conditions
      encountered in the newly infected host before they can multiply sufficiently to
      produce the symptoms of disease. It is further suggested that epidemics may arise
      because the infectious agent is passed from person to person in the ascending
      stage of the disease and thus enters new hosts in a state of maximum resistance
      to the natural antibodies of such individuals. When early contacts are avoided,
      epidemics tend to subside because the infectious agent is weakened by the action
      of acquired antibodies during the period of convalescence.

PMID- 19868031
TI  - THE DIFFERENTIATION OF CELLS AS A CRITERION FOR CELL IDENTIFICATION, CONSIDERED
      IN RELATION TO THE SMALL CORTICAL CELLS OF THE THYMUS.
AB  - The main problem which has been considered in this paper is the identification of
      the small thymus cells. Cells resembling ?A infiltrate the cortical layer of the
      thymus. Whether these cells are true lymph cells, or whether they merely
      represent a disguised epithelial cell, could not be solved either by purely
      histological or by histo- and embryogenetic studies. Text-fig. 1 gives a scheme
      for the differentiation of the small thymus cells and the small lymphocytes,
      which led to a conception of the lymphoid nature of the small thymus cells. On
      the left of the figure is shown the origin and the normal differentiation of the
      small lymphocytes and their mother cells in birds. The source of the lymphoid
      cells is the loose mesenchyme. The small lymphocytes (S. Lmc.), normally situated
      in the spleen, in the connective tissue, and in the bone marrow, appear as
      differentiation products of the lymphoid hemocytoblasts (L. Hbl.), especially
      when the latter multiply intensely in a limited space, become smaller (S. L.
      Hbl.), and finally change their morphological structure. The small lymphocytes
      may themselves under definite conditions undergo further differentiation and
      develop into plasma cells (Plc.) and into granular lymphocytes (Gr. Lmc.),
      specific for birds. The mother cells of the small lymphocytes, the lymphoid
      hemocytoblasts, on the other hand, differentiate in granulopoietic organs
      (spleen, bone marrow) into granulocytoblasts (Grbl.) and granulocytes (Grc.
      (Lkc.) ). The histogenetic study of cell ?A shows that its nearest stem cells are
      represented by the cells ?B and ?C (page 93). The striking similarity in the
      structure of cell ?A with that of the small lymphocyte (on the left of the text
      figure), as well as the analogy of the process of its differentiation, at the
      expense of cells ?B and ?C, with the normal origin of the small lymphocytes, has
      led many investigators to accept the mesenchymal origin of the small thymus
      cells. According to this view, cell ?A becomes a true small lymphocyte. In
      addition to this is the observation of an invasion of the epithelial thymus
      anlage by mesenchymal elements. According to the transformation theory cell ?A
      has become a disguised epithelial cell. The same was admitted for their stem
      cells ?B and ?C. As mentioned above, many characteristic morphological features
      of cell structure were shown to be not as essential as previously admitted. Nerve
      cells and epithelial and connective tissue cells may all assume a spherical shape
      in a liquid medium. How then are we to regard the small thymus cell ?A ? If the
      mother cell of the thymus cell ?A is really a lymphoid hemocytoblast, it must
      possess the differentiation potentialities of a true lymphoid hemocytoblast; it
      must have the faculty of differentiating not only into small lymphocytes but also
      into granulocytoblasts (Grbl.'') and further into granulocytes (Grc. (Lkc.)'').
      If the small thymus cell ?A is a small lymphocyte it must under definite
      conditions be able to differentiate in the directions characteristic of true
      small lymphocytes; namely, into plasma cells (Plc.'') and into granular
      lymphocytes (Gr. Lmc.''). The existence of these possibilities for
      differentiation of the small thymus cells ?A and their stem cells ?C have been
      experimentally proved by this study. It has been shown that the mother cell ?C
      may under certain conditions proliferate intensely and differentiate into
      granulocytoblasts and granular leukocytes. This is probably due to the
      stimulating action of certain metabolic products of the grafted spleen cells. It
      has been also shown that the small thymus cell ?A may differentiate
      physiologically into a granular lymphocyte, and under administration of x-ray
      into a plasma cell. All the changes observed on the small thymus cells and their
      mother cells apply under equal conditions to the lymphoid hemocytoblasts and to
      the true small lymphocytes in the regions of the organism where these cells are
      present.

PMID- 19868032
TI  - A CONTRIBUTION TO THE CHEMOTHERAPY OF TUBERCULOSIS : FIRST EXPERIMENTAL REPORT.
AB  - JUDGING FROM THE MACROSCOPIC AND MICROSCOPIC STUDY OF THE ANIMALS TREATED WITH
      THE LIQUID, ITS ACTION UPON THE TUBERCULAR LESIONS SEEMS TO BE ABOUT AS FOLLOWS:
      The effect of a single injection upon the lesions is either negative or
      inconspicuous. But after repeated injections of the preparation the congestion
      and leukocytic infiltration about the lesions are markedly decreased, the cheesy
      material resulting from degeneration of the lesions and other degeneration
      products are in process of absorption, and young connective tissue is being
      actively produced in the periphery. While these changes are taking place the
      number of the bacilli is also being reduced until finally they can no longer be
      detected on microscopic examination. Hence it appears that while the preparation
      may lack bactericidal action in vivo powerful enough to destroy all the bacilli
      at one injection, yet repeated infusions may nevertheless bring about the
      destruction of all the bacilli and the modification of the tubercular lesion into
      that of the suspended stage or even into the healed condition. Whether,
      therefore, the preparation brings about these results directly by killing the
      bacilli or indirectly by favoring the healing processes of the body, nevertheless
      it has power to inhibit the growth of or annihilate entirely the bacilli in vivo.
      The experiments reported leave no doubt that Liquid D is capable of bringing
      about the healing of experimental tubercular lesions; but thus far that most
      important problem in chemotherapeutics, namely, the extent of the cure produced,
      has not been solved. The experiments indicate that sterility of the tissues as
      far as microscopic examinations go has been secured; but microscopic examination
      is not after all an absolute test of sterility. In order to test this point,
      emulsions were made of the lungs, liver, spleen, and other organs of Treated
      Animals 134 and 135 (Table VII), and they were inoculated into the abdominal
      cavity of guinea pigs. Some of the animals receiving the emulsion developed
      tuberculosis, and therefore absolute sterility of the treated animals had not
      been obtained in these instances. The problem of the destination and distribution
      of the preparation in the body of the treated animal, as well as its action
      against the tubercle bacilli, lesions, and the tubercular organs of the infected
      guinea pigs, is now being studied further with results to be reported at some
      future time.

PMID- 19868033
TI  - A CONTRIBUTION TO THE CHEMOTHERAPY OF TUBERCULOSIS : FIRST CLINICAL REPORT.
AB  - A general review of the cases will, I think, indicate that the preparation
      greatly improves or apparently cures pulmonary and surgical tuberculosis in the
      first and second stages, and that it seems also to produce beneficial effects
      upon the disease in the third stage. The duration of these beneficial effects is
      still to be established by more numerous trials and many years of observation.
      The preparation must be given intravenously, and the doses must be increased or
      decreased according to the age and constitution of each patient (page 156).
      Moreover, it should be borne in mind that the pathological phenomena and the
      constitution of each patient have much to do with the determination of the dose.
      The manner of action of the preparation is not yet entirely clear. But if it acts
      primarily upon the tissues which bear the tubercular lesions and then indirectly
      against the germ, as I assume at present, the activity which the tissues exert
      will have much to do with the efficacy of the preparation. If this hypothesis is
      correct, the minimum doses (10 to 12 mg.) will be best suited to a patient who is
      greatly emaciated, and should be gradually increased as the reactions,
      pathological processes, nutrition, etc., indicate. In any case, the dose of the
      preparation must be determined by the condition and constitution of the patient.
      In animal experiments I have been fortunate enough to obtain results which no
      other preparation has given. The clinical application and the establishment of
      its full efficacy in human cases must be left to the physician.

PMID- 19868034
TI  - THE TREATMENT OF TUBERCULOSIS WITH CYANOCUPROL.
AB  - Cyanocuprol is markedly effective in tuberculosis, and we believe that it will
      play an important part in clinical medicine. It may be used more generally than
      tuberculin. The amount of the dose is closely related to the reaction and the
      final results. It should be determined for each patient after a careful
      examination of his symptoms. The maximum dose of 8.5 cc. should in no case be
      exceeded. The shortest interval between injections should be 2 weeks. If the drug
      is given after a shorter interval, no improvement is observed and the effects are
      sometimes dangerous. In order to obtain the best results the patient should be
      placed under conditions of complete physical and mental rest after the injection;
      this applies even to light cases. Care should also be taken to secure rest for
      the lesion. During the period of the treatment irritants to the lesion, such as
      potassium iodide or tuberculin, should be avoided; apricot juice, guaiacol and
      its derivatives, and iodol are contraindicated. No marked idiosyncrasy has been
      noted and no accumulative effects have been observed.

PMID- 19868035
TI  - THE TREATMENT OF LEPROSY WITH CYANOCUPROL.
AB  - This brief report deals with six cases of leprosy in which cyanocuprol has been
      administered with what appear to be beneficial effects. The treatment is being
      continued in still other cases.

PMID- 19868036
TI  - A NON-GAS-PRODUCING STRAIN OF THE HOG-CHOLERA BACILLUS ISOLATED FROM AN OLD
      LABORATORY CULTURE.
AB  - In a stock culture of the hog-cholera bacillus, which was passed through a series
      of rabbits 14 years ago, an organism was found that differs from the original
      culture in that it fails to form gas from the carbohydrates that are usually
      attacked by this organism, while acid formation persists. This new strain is
      agglutinated by an anti-hog-cholera bacillus serum and produces in rabbits and
      mice a disease similar to that caused by the typical cultures. The failure to
      form gas has persisted over a period of 18 months and all attempts to cause the
      strain to revert to the original condition have failed. It resembles in many
      respects Bacillus typhosus and it may be that some of the so called typhoid
      cultures that are not agglutinated by antityphoid serum are non-gas-producing
      paratyphoids. Attempts to produce a similar change in a more recently isolated
      culture of the hog-cholera bacillus by means of animal passages and changes in
      the environment have been negative.

PMID- 19868037
TI  - THE EFFECTS OF EXPOSURE TO COLD UPON EXPERIMENTAL INFECTION OF THE RESPIRATORY
      TRACT.
AB  - 1. Respiratory infection of rabbits with Bacillus bovisepticus (snuffles) is
      favored by chilling the animals after they have been accustomed to heat. 2. The
      character of this disease, which occurs frequently in rabbits under natural
      conditions, makes the application of the experimental results to similar
      respiratory conditions in man less open to objection than in similar experiments
      with other infections. 3. The weight of experimental evidence, including our own,
      does not justify the elimination of exposure to cold as a possible though
      secondary factor in the incidence of acute respiratory disease. 4. From the
      limited data of our last two experiments it is suggested that any marked change
      of temperature predisposes rabbits to this infection, the severity of which
      varies with the amount of change, and that a change from low to high temperature
      has an even more marked effect than that from high to low.

PMID- 19868038
TI  - STUDIES ON HETEROGENEOUS HEMOLYTIC SERA.
AB  - Red corpuscles with nuclei contain heterogeneous sheep antigen when the organs of
      the same animal possess it. The sera in question contain not only heterogeneous
      hemolysins but also heterogeneous agglutinins. The hemolytic sera of rabbits
      immunized with hen red corpuscles are toxic to guinea pigs and kill them, the
      clinical picture being that of anaphylactic shock. Heterogeneous hemolysins are
      obtained by means of non-toxic antigen (hen red corpuscles injected into veins of
      rabbits). This fact refutes the theory of Friedberger, who attributed the
      antigenic power of a suspension of organs to its toxic character.

PMID- 19868039
TI  - THE EFFECTS OF SERUM TREATED WITH AGAR.
AB  - The intravenous injection of horse serum, kept for 2 hours at 38 degrees C. in
      the presence of one-fifth of its volume of a suspension of 0.5 per cent agar in
      physiological salt solution and then separated from the agar by
      centrifugalization and filtration, produces in normal rabbits in adequate doses a
      considerable and prolonged fall in the blood pressure, expulsion of feces, a
      diminished coagulability in the carotid blood, and at times accelerated
      respiration; that is, the various symptoms observed after the intravenous
      injection of horse serum in a seroanaphylactized rabbit. Horse serum previously
      kept for 30 minutes at 56 degrees C. and then treated with agar in the manner
      described above, when injected intravenously into a normal rabbit will have no
      more effect on the arterial pressure, on the intestinal movement, on the
      respiratory rate, or the coagulation of arterial blood than the introduction of
      horse serum into the veins of a normal rabbit.

PMID- 19868040
TI  - AN EXPERIMENTAL STUDY OF CIRCUMSCRIBED DILATION OF AN ARTERY IMMEDIATELY DISTAL
      TO A PARTIALLY OCCLUDING BAND, AND ITS BEARING ON THE DILATION OF THE SUBCLAVIAN
      ARTERY OBSERVED IN CERTAIN CASES OF CERVICAL RIB.
AB  - 1. A partially occluded artery may dilate distal to the site of constriction. 2.
      The dilation is circumscribed. 3. When the constriction has been either slight in
      amount or complete, dilation has not been observed. 4. The dilation was greatest
      when the lumen of the artery (the aorta) was reduced to one-third or perhaps one
      fourth of its original size (Figs. 8 and 11). 5. Dilation or aneurysm of the
      subclavian artery has been observed twenty-seven or more times in cases of
      cervical rib. 6. The dilation of the subclavian is circumscribed, is distal to
      the point of constriction, and strikingly resembles the dilation which we have
      produced experimentally. 7. The genesis of the experimental dilation and of the
      subclavian dilation occurring with cervical rib is probably the same. 8. When the
      lumen of the aorta is considerably constricted the systolic pressure may be
      permanently so lowered and the diastolic pressure so increased that the pulse
      pressure is greatly diminished. 9. The experimentally produced dilations and the
      aneurysms of the subclavian artery in cases of cervical rib are probably not due
      to vasomotor paralysis, trauma, or sudden variations in blood pressure. 10. The
      abnormal, whirlpool-like play of the blood in the relatively dead pocket just
      below the site of the constriction, and the lowered pulse pressure may be the
      chief factors concerned in the production of the dilations. 11. Intimal surfaces
      brought, however gently, in contact by bands or ligatures do not, in our
      experience, unite by first intention, for the force necessary to occlude the
      artery is sufficient to cause necrosis of the arterial wall. 12. Bands, rolled
      ever so tightly, do not rupture the intima. 13. The death of the arterial wall
      having been brought about by the pressure of the band, a gradual substitution of
      the necrotic tissue takes place, the new vessels penetrating it from both ends.
      It is, I believe, in this manner that an artery becomes occluded, and it is thus
      that a fibrous cord forms within the constricting band.

PMID- 19868041
TI  - PARTIAL OCCLUSION OF THE AORTA WITH THE METALLIC BAND. OBSERVATIONS ON BLOOD
      PRESSURES AND CHANGES IN THE ARTERIAL WALLS.

PMID- 19868042
TI  - DISTORTION OF THE MALARIAL PARASITE. AN INTERPRETATION OF "PLASMODIUM TENUE"
      (STEPHENS.).
AB  - 1. The correct interpretation of the form described by Stephens under the name of
      Plasmodium tenue is as follows: It is not a new species of parasite or an ameboid
      form, but a parasite attached to the external surface of red corpuscles and
      distorted by technique. 2. Evidence against a new species of parasite is: (a)
      they may be found in all known malarial infections and at any stage in the
      development of the parasite; and (b) they show evidence of distortion. 3.
      Evidence against ameboid forms and in favor of parasites distorted by technique
      is: (a) they may be found in but one of the two cover-slips prepared
      simultaneously; (b) they may be found in certain definite groups in various parts
      of a film which otherwise contains normal appearing parasites; (c) in rich
      infections, containing many disforted forms, they may be found in certain parts
      of a film, all distorted in one direction, the infected corpuscles and those
      adjacent to them showing no evidence of injury; and (d) two or more parasites
      attached to one red corpuscle may be seen to be distorted in one direction, or to
      have nuclei similarly distorted. 4. Three general types of distorted parasites
      may be recognized: (a) parasites with nuclei distorted and cytoplasm unaltered or
      but slightly distorted; (b) parasites with cytoplasm distorted and nuclei intact
      or but little disturbed; and (c) parasites with both nuclei and cytoplasm
      slightly or markedly distorted. 5. Red corpuscles to which distorted parasites
      are attached usually appear to be flattened out with slightly irregular outline,
      but parasites may be more or less distorted without any apparent change in the
      infected corpuscle. 6. Parasites with well stained chromatin and faded cytoplasm,
      or parasites with well stained cytoplasm and faded chromatin, may be found in
      specimens containing well stained parasites. It is usually possible to restain
      these specimens bringing out the faded cytoplasm belonging to the well stained
      chromatin or the lost chromatin belonging to the well stained cytoplasm.

PMID- 19868043
TI  - THE FORMATION OF METHEMOGLOBIN BY STREPTOCOCCUS VIRIDANS.
AB  - Cultures of Streptococcus viridans when brought into contact with red blood
      corpuscles have the power of transforming oxyhemoglobin into methemoglobin. The
      reaction occurs only in the presence of living streptococci when they are able to
      carry on their metabolic activities. The intensity of the reaction runs roughly
      parallel with the period of growth and multiplication of the bacteria and
      gradually diminishes and disappears as growth ceases. There is no apparent
      relation between the activity of a given strain of Streptococcus viridans in
      producing methemoglobin and its source or virulence. If the streptococci are
      suspended in salt solution they are unable to change oxyhemoglobin into
      methemoglobin unless some nutrient substance is present. Of the various nutrient
      substances tested dextrose is the most efficient in enabling the organisms to
      bring about the reaction. The reaction does not occur in the absence of oxygen,
      and is retarded by an excess of oxygen. Substances which tend to reduce the
      metabolic activities of the bacteria to a minimum exert an inhibitory action on
      methemoglobin formation. While not definitely proving it to be so, the results
      obtained in the above experiments strongly support the supposition that the
      reaction is not due to injurious substances produced by the bacteria or to
      products arising from the decomposition of the nutrient material present, but
      rather to the metabolic activities of the bacteria themselves when they are
      surrounded by environmental conditions which render growth and multiplication
      possible. The exact chemical nature of the change of oxyhemoglobin to
      methemoglobin is not known, but it is probably an oxidation process or a
      combination of reduction and oxidation processes, as pointed out by Heubner. As
      Cole has shown, the action of aminophenol is of great interest in this
      connection, in that it acts like a catalytic agent in being able to transform
      much more hemoglobin into methemoglobin than would be possible if the reaction
      were a simple molecular one. The metabolic activities of bacteria are largely in
      the nature of oxidation and reduction processes. The transformation of
      oxyhemoglobin into methemoglobin by streptococci of the viridans type, therefore,
      may be analogous to the action of such substances as aminophenol, and the
      reaction may be due to the active oxidation and reduction processes occurring in
      the neighborhood of the bacterial cells. The failure of the reaction to occur in
      the absence of oxygen and its retardation in the presence of an excess of oxygen,
      both with streptococci and with pneumococci (Cole) would seem to support this
      theory. Such results, however, may be due to the abnormal conditions surrounding
      the bacteria with consequent inhibition of their metabolic activities. Cole
      concluded as the result of his study of methemoglobin formation by pneumococci
      that since bacteria may injure red blood cells apparently by disturbances in
      oxidation in the immediate neighborhood of the organisms rather than by the
      production of a definite toxin, it is possible that bacteria may injure other
      tissue cells in a like manner and that the pathological effects produced by these
      bacteria may be explained on this basis. The experimental results recorded above
      have shown that the formation of methemoglobin by Streptococcus viridans in no
      way differs from its formation by pneumococci, and they lend support to the
      theory that bacteria may be injurious to tissues because of the disturbances in
      oxidation brought about by the metabolic activities of the organisms, especially
      those associated with growth and multiplication. It is believed that this theory
      may be particularly applicable to the pathological effects caused by
      Streptococcus vindans because the lesions produced by it, whether single or
      multiple, both in man and in experimental animals, are prone to be localized and
      associated with the actual presence of the streptococci in the lesions.

PMID- 19868044
TI  - A FURTHER STUDY OF THE GASTRIC ULCERS FOLLOWING ADRENALECTOMY.
AB  - Acute gastric ulcers are found in a large percentage of animals dying from acute
      adrenal insufficiency. In dogs in which a portion of the jejunum had been
      transplanted some time previous to the removal of the adrenals, the gastric
      mucosa showed more marked changes than the transplanted jejunal mucosa. This
      tends to show that the gastric juice as the cause of the ulcer is but a secondary
      although necessary factor.

PMID- 19868045
TI  - AGGLUTINATION OF TREPONEMA PALLIDUM IN HUMAN SYPHILIS.
AB  - The results observed with this strain of Treponema pallidum may be stated as
      follows: 1. Normal human serum did not agglutinate this culture of Treponema
      pallidum in dilutions of 1:5 or higher; equal parts of treponema culture and
      normal serum (dilution 1:2) resulted in agglutination in about 50 per cent of the
      sera. With the strain of Treponema pallidum used in this study specific
      agglutination was not considered as having occurred unless observed in dilutions
      of 1:5 or higher. 2. The agglutinating power of the sera of non-syphilitic
      persons suffering with various infections was not higher than that of normal
      sera. 3. Traces of specific agglutinin for this culture of Treponema pallidum
      were found in the sera of persons late in the primary stage of syphilis. 4. In
      the secondary stage of syphilis about 58 per cent of sera showed the presence of
      a demonstrable amount of agglutinin in dilutions of 1:5 and higher; in no
      instance, however, was agglutination in evidence in dilutions higher than 1:20.
      5. In tertiary and latent syphilis, mostly infections of the central nervous
      system, agglutination in dilutions of 1:5 and higher was found with about 84 per
      cent of sera. The highest concentration of pallida agglutinin in the blood serum
      was found in the later stages of syphilis. 6. The formation of agglutinin for
      culture Treponema pallidum in human syphilis is probably tardy and does not reach
      a state of high concentration. 7. There was no direct relation between the
      presence of the Wassermann antibody and agglutinin for this strain in the sera of
      syphilitics. The former appears in the body fluids earlier and is probably in
      higher concentration in all stages of syphilis; while agglutination is most
      likely to occur with Wassermann positive sera, it may be occasionally observed
      with sera yielding negative Wassermann reactions. Likewise strongly Wassermann
      positive sera may not contain demonstrable amounts of agglutinin. 8. It is
      probable that different strains of pallida vary in susceptibility to
      agglutination. For example, in the first investigation on agglutinins for
      Treponema pallidum by Kolmer, the sera of syphilitics in different stages of the
      disease did not cause agglutination of one of Noguchi's strains in dilutions of
      1:20 and higher, whereas the strain used in the present study was frequently
      agglutinated in this dilution by sera from a similar group of patients. As shown
      by Zinsser, Hopkins, and McBurney, virulent pallida from human lesions resist
      agglutination to a remarkable degree. 9. While further studies are necessary to
      establish the practical value of agglutination in the diagnosis of human
      syphilis, we believe that with a suitable culture or cultures well marked
      agglutination of Treponema pallidum in dilutions of 1:5, or better 1:10 and
      higher, indicates pallida infection and may prove of value in the diagnosis of
      isolated cases, particularly in the later stages. Investigations bearing upon the
      relation of agglutinins for culture pallida to immunity in syphilis will be given
      in a separate communication (16).

PMID- 19868046
TI  - A STUDY OF THE PHYSIOLOGICAL ACTIVITY OF ADENOMATA OF THE THYROID GLAND, IN
      RELATION TO THEIR IODINE CONTENT, AS EVIDENCED BY FEEDING EXPERIMENTS ON
      TADPOLES.
AB  - It seems evident from the foregoing experiments that the so called tumors
      (adenomata) of the thyroid possess the property of taking up iodine and
      metabolizing it into the active combination in the same way that the non-tumorous
      thyroid tissue does, although not so readily nor to the same degree, and the
      action on tadpoles of feeding desiccated tumorous thyroid tissue does not differ
      qualitatively from feeding desiccated non-tumorous thyroid tissue. The action in
      either case depends upon the iodine (active iodine) content, and in the case of
      the adenomata bears no constant relation to the state of their growth or
      differentiation. Examination of Tables II and III shows that in the main this is
      true. There are, however, certain discrepancies as to time of death, appearance
      of first forelegs, degree of emaciation, and rate of growth in certain dishes of
      the series, the action being not quite parallel to the iodine content. Some of
      these discrepancies may be explained in part by accidents of feeding, slight
      differences in size, age) and susceptibility of the different tadpoles receiving
      the same thyroid, and also by the variations in the amount of thyroid consumed by
      the different individuals in the same dish. Lenhart has shown that the action of
      the same thyroid varies with the quantity fed. Another important factor which has
      to be considered is the condition of the iodine itself. It was suspected at the
      time of these experiments that the iodine might be present in an active and an
      inactive form, but no satisfactory proof of this assumption, at the beginning of
      these experiments, was at hand. Support of this point has been afforded by the
      work of Kendall on the isolation of the active principle of thyroid and the
      separation of the iodine into two fractions. Since the completion of our
      experiments Marine has demonstrated by means of perfusion experiments in vivo and
      in vitro that iodine is rapidly taken up by the thyroid cells, and though the
      iodine increase in the perfused lobe may be 1,000 per cent in 2 hours as compared
      with the control lobe, yet the action on tadpoles is no greater. It then becomes
      an important question to determine the time required by the thyroid to take up
      inorganic iodine and manufacture it into the active thyroid principle. It is
      known that iodine is rapidly taken up by the thyroid, and in man the iodine
      content of the thyroid is subject to greater variations than in animals on
      account of the prevalent therapeutic use of iodine and the iodides in goiter and
      other conditions; even the iodine used in preparing patients for operations would
      increase the iodine content of the thyroid in a short time, so that one might
      expect such variations in the action of a given thyroid preparation fed to
      tadpoles as appear in these experiments. In this connection it is interesting to
      note (Table II) that Thyroid 20 with 4.31 mg. of iodine was only slightly more
      active than No. 5 with 1.31 mg. of iodine. Two possibilities have to be
      considered here. First, No. 20 may have active iodine slightly greater than 1.31
      mg. and the balance present as inactive iodine. Second, No. 5 with 1.31 mg. of
      iodine might represent the maximum possible effect under the conditions of the
      experiment and a larger quantity of active thyroid iodine could produce no
      greater effect. Of course with the lower iodine contents the variations in
      effects might well come within the limits of errors of observation. Also the
      percentage error would be greater in the iodine determinations, accidents of
      feeding, etc. Our conclusions as to the effect of feeding desiccated thyroid to
      tadpoles agree in general with those of Lenhart. The action of the thyroid
      depends not upon a specific stimulus to differentiation but upon a stimulation of
      metabolism in general in proportion to the active iodine and the quantity
      consumed. High iodine contents produce rapid emaciation, at the same time
      resulting in differentiation even in tadpoles dying in 8 to 12 days. Low iodine
      contents result in differentiation at an earlier period than the controls.
      Tadpoles fed on thyroid with practically no iodine grow better than the controls,
      in this instance the thyroid acting simply as a food. Finally, the interest that
      the results of these experiments may have in connection with the question of
      function in tumor tissue should be pointed out. To those who hold that tumor
      lacks the capacity for physiological function, the adenomata of the thyroid could
      not be consistently regarded as tumors. To those who hold physiological function
      as a possible property of tumor tissue, the adenomata might be regarded as
      tumors. Future studies might warrant a recognition of different grades or degrees
      of tumor. On this basis the fetal adenoma (very little differentiation) might
      represent a higher degree of tumor than the diffuse colloid or simple adenomatous
      thyroid in which the adenomatous nodules are present to a great extent throughout
      the whole gland and are well differentiated. It is certain that there are all
      grades and degrees of growth and differentiation in the life history of fetal
      adenomata of the thyroid, from the pure fetal, undifferentiated adenoma with
      little or no iodine to the simple or colloid adenoma, well differentiated and
      with varying amounts of iodine approaching that of normal thyroid.

PMID- 19868047
TI  - SPONTANEOUS DIABETES IN A DOG.
AB  - The picture is one of a true diabetes mellitus, first attracting attention after
      miscarriage. Although the G : N ratio sank from 3 : 1 on 10 gm. of nitrogen to
      1.7 : 1 after 3 days' fasting, the disease progressed steadily in spite of a long
      continued carbohydrate-free diet. Together with the usual complications of
      diabetes, a malignant tumor of the thymus developed, so that after 5 months'
      observations a slow death was forestalled by chloroform. The most striking
      feature at autopsy was the large, apparently normal pancreas, which exhibited
      histologically marked changes in the islands of Langerhans, extreme hydropic
      degeneration and exhaustion of granules, involving both alpha and beta cells, but
      especially the latter, and replacement of some islands by fibrous tissue.

PMID- 19868048
TI  - TECHNIQUE OF CULTIVATING HUMAN TISSUES IN VITRO.
AB  - 1. Unmodified human plasma is not a satisfactory culture medium for human tissues
      owing to the susceptibility of human fibrin to digestion by tissue ferments. The
      necessary framework is thus destroyed before the cells begin to migrate. The
      difficulty can be overcome by adding to human plasma or serum a small quantity of
      fowl or pigeon plasma, the fibrin of which is highly resistant to digestion.
      Human tissues have been propagated in this medium for several months through
      subcultures, and growth in vitro can probably be maintained indefinitely. 2.
      Human tissues show no greater sensitiveness to changes in temperature and
      mechanical injury associated with preparation of cultures than those of lower
      animals. They may be preserved in an ordinary ice box at 10-15 degrees C. as long
      as 6 or 8 days. Tissues obtained at operation give best results, but pieces of
      organs removed at autopsy 1 to 4 hours after death sometimes show active growth.
      3. The presence of normally existing iso-antibodies (agglutinins and hemolysins)
      in human serum is without influence on the growth of human tissues in vitro. In
      other words, autogenous serum has no advantage in tissue cultures over homologous
      serum.

PMID- 19868049
TI  - A STUDY OF SERUM SALVARSANIZED IN VITRO.
AB  - 1. Addition of salvarsan to serum in vitro produces a spirocheticidal mixture
      which is increased in potency by heating. 2. The heated serum of salvarsan
      treated patients is more spirocheticidal if it has been in contact with the clot
      over night than if it has been separated immediately after coagulation. This is
      not true with the serum from blood which has been salvarsanized in vitro. 3. The
      addition of salvarsan directly to serum produces a more potent mixture than
      results from the serum from blood to which salvarsan has been added in equivalent
      amounts. 4. The increase in activity of salvarsanized serum produced by heating
      to 56 degrees C. is due in part to the removal of inhibitory substances in the
      serum and in part to a direct increase in spirocheticidal power in the heated
      salvarsan. 5. Both salvarsanized and neosalvarsanized serum are rendered more
      spirocheticidal by heating. 6. A more active spirocheticidal mixture is produced
      by mixing small amounts of salvarsan with the serum of a salvarsan-treated
      patient than by mixing the same amount with normal serum.

PMID- 19868050
TI  - THE LATENT PERIOD IN THE GROWTH OF BACTERIA.
AB  - 1. Cultures of Diplococcus pneumoniae, Bacillus coli, Bacillus fluorescens
      liquefaciens and Bacillus prodigiosus, when grown in meat infusion broth exhibit
      an initial latent period when the culture used for inoculation is no longer
      growing at its maximum rate; if, however, the culture is growing at its most
      rapid rate the bacteria, upon subculture, show no latent period but continue to
      multiply at the same rate as that of the parent culture. 2. If broth cultures of
      pneumococcus are centrifuged at the beginning of the period of maximum rate of
      growth, the bacteria remaining in the supernatant fluid continue to grow at a
      rapid rate upon further incubation; if, however, the culture is centrifuged at
      the end of the period of maximum rate of growth, those bacteria which remain in
      the supernatant fluid show a prolonged latent period, during which many of the
      organisms die. While the death of these bacteria is taking place the process
      follows closely the law of unimolecular reactions. 3. Actively growing
      pneumococci inoculated into the supernatant fluid from a 4 day culture of the
      same strain continue to grow rapidly for an appreciable time after inoculation.
      4. Filtrates from 24 hour cultures of pneumococcus inhibit the further growth of
      actively growing pneumococci when the latter are inoculated into such filtrates.
      This inhibitory action of the filtrates is lost in part as the culture from which
      the filtrate is obtained is allowed to incubate longer. 5. Actively growing
      pneumococci, after exposure at low temperatures to the action of the filtrate of
      a 24 hour broth culture of the same strain, show a greater lag than the controls.
      6. The foregoing facts offer strong support for the view that lag is an
      expression of injury which the bacterial cell has sustained from its previous
      environment.

PMID- 19868051
TI  - A RAPID METHOD FOR THE DIAGNOSIS OF RENAL TUBERCULOSIS BY THE USE OF THE X-RAYED
      GUINEA PIG.
AB  - It is possible to reduce the resistance of guinea pigs to tuberculosis by x-ray
      exposures, so that when animal inoculation is required for a diagnosis a much
      quicker result may be had than by the use of normal animals. In renal
      tuberculosis when it is necessary to resort to the use of animals, it ordinarily
      requires from 5 to 7 weeks, while by the use of x-rayed guinea pigs the diagnosis
      can be made in from 8 to 10 days. The resistance can be sufficiently lowered by
      one massive dose of x-ray administered either shortly before or after the
      inoculation of the material to be tested. The lesions are so marked in these
      animals that the diagnosis is certain after the interval indicated above.

PMID- 19868052
TI  - CICATRIZATION OF WOUNDS : I. THE RELATION BETWEEN THE SIZE OF A WOUND AND THE
      RATE OF ITS CICATRIZATION.
AB  - 1. A method for measuring the area of a wound not geometric in form is described.
      2. The rate of cicatrization of a wound is greater at the beginning than at the
      end of the period of repair. It depends on the area rather than on the age of the
      wound. There is a constant relation between the size of a wound and the rate of
      cicatrization. The larger the wound the greater is the rate of cicatrization. Two
      wounds of different size have a tendency to become equal. 3. The rate is
      proportional to the area, but diminishes less rapidly than the area. 4. The
      process of contraction is the more important factor in the repair of a wound.
      Epidermization completes the work of contraction. After the wound is healed, the
      cicatrix as a rule expands. 5. The curve representing the diminution of the size
      of an aseptic wound while it cicatrizes is regular and geometric.

PMID- 19868053
TI  - CICATRIZATION OF WOUNDS : II. MATHEMATICAL EXPRESSION OF THE CURVE REPRESENTING
      CICATRIZATION.
AB  - The cicatrization of sterile wounds may be studied in the same way as an ordinary
      physicochemical phenomenon. It is possible, therefore, to express the law of
      cicatrization by a mathematical equation as soon as an accurate measure of the
      wound can be obtained. By means of the equation, a curve is obtained which
      represents the theoretical evolution of the cicatrization of a wound. This curve,
      being an expression of what should happen on a normal wound, healing aseptically,
      on a normal man, is a daily point of comparison to what appears actually on the
      observed wound, and allows one to study accurately the fluctuations of
      cicatrization on a given individual, and the action of different dressings and
      antiseptic substances.

PMID- 19868054
TI  - CICATRIZATION OF WOUNDS : III. THE RELATION BETWEEN THE AGE OF THE PATIENT, THE
      AREA OF THE WOUND, AND THE INDEX OF CICATRIZATION.
AB  - The first article of this series showed that it was possible to express
      mathematically the phenomenon of cicatrization. The principal point consisted in
      determining by means of an equation, a constant, or index, characterizing each
      wound. The calculation had to be made for each patient for each wound, and
      required two observations, 4 days apart. The index having proved to be a
      continuous function of the size of the wound and of the age of the patient, of
      the form See PDF for Equation where S is the area, i the index, a a decimal
      exponent, and K a constant, it was then possible to draw a chart by means of
      which this index i could be obtained without calculation. The advantage of the
      new way of determining the index is, above all, that this index is a general,
      average, normal index, and no longer an individual index. Hence, the differences
      between the observed rate of cicatrization of man and the normal rate may give
      some indication of the general state of the patient. Another advantage is that
      the determination of the index is no longer controlled by the temporary accidents
      which may happen between the two observations of S and S'.

PMID- 19868055
TI  - THE PROPHYLAXIS OF WEIL'S DISEASE (SPIROCHAETOSIS ICTEROHAEMORRHAGICA).
AB  - We have already described briefly the portals of entry and of excretion of the
      pathogenic spirochetes. We may mention here that we have twice prevented
      epidemics by disinfection of the ground and the removal of the inundated water in
      certain places in coal mines. In one mine 19 out of 50 workmen, and in another 9
      out of 30 workmen came down with Weil's disease in about 2 weeks. We have already
      pointed out that the period during which the pathogenic spirochetes are excreted
      in the urine continues, as a rule, for 40 days, and that we must, therefore,
      apply disinfection for at least 40 days after the first appearance of the
      disease. Lately we have found that in 21 cases out of 24 the spirochetes were
      excreted in the urine for 40 days, in one case until the 42nd day, in one case
      until the 45th day, and in still another case until the 63rd day. Another
      important fact concerning the prophylaxis which has been brought out is that both
      house and ditch rats (brown) carry virulent Spirochaeta icterohamorrhagae, the
      causal spirochete of Weil's disease, in their kidneys. Miyajima has reported that
      field rats have the pathogenic organisms in their kidneys; he will report these
      findings in detail later. The spirochetes which he described are less virulent
      than ours. On his advice we have carefully examined house and ditch rats in the
      city and rats in the coal mines of Kyushu, where Weil's disease prevails, and
      found that 39.5 per cent carried highly virulent pathogenic spirochetes in their
      kidneys, thus confirming Miyajima's experiments. The kidneys were examined
      microscopically under the dark-field microscope, and in the cases in which we did
      not find the pathogenic spirochete, we made inoculations into guinea pigs. Thus
      we found Spirochaeta icterohaemorrhagiae microscopically in the kidneys or in the
      urine in 32.4 per cent, and by means of inoculation in 7 per cent, making a total
      of 39.5 per cent carrying the pathogenic organisms, out of a total number of 86
      rats examined. In some instances, rats were made to bite guinea pigs and in two
      instances caused Weil's disease. Among fifty-five patients in our clinic, twelve
      were cooks; and in Europe many cases arise among butchers-indicating the relation
      of the disease to rats. Moreover, during the present year we observed two
      patients who acquired Weil's disease, one in 1 week, the other 8 to 9 days after
      they had been bitten by rats. These facts point to a relation between Weil's
      disease and rats. The infection is transmitted probably from rats to man by means
      of the urine of the rats, directly or indirectly. On the injection of 0.1 gm. of
      rat urine which contains Spirochaeta icterohaemorrhagiae into the peritoneal
      cavity of guinea pigs, the infection arises, while the injection of the liver or
      the blood of the rats into guinea pigs does not produce the typical disease. The
      finding that the kidneys of rats contain the pathogenic organisms of the disease
      is important from the point of view of prophylaxis. The large number of rats in
      the trenches of the European battle-fields suggests the possibility that many
      cases of Weil's disease may arise. We shall report on this point in more detail
      later.

PMID- 19868056
TI  - THE SERUM TREATMENT OF WEIL'S DISEASE (SPIROCHAETOSIS ICTEROHAEMORRHAGICA).
AB  - Horses immunized with cultures of Spirochaeta icterohaemorrhagiae yield an immune
      serum having therapeutic properties. With rare exceptions the serum destroys
      completely the spirochetes contained in the circulating blood. The development of
      antibodies is promoted by the serum injections. The number of spirochetes in the
      organs is reduced by the treatment. Secondary manifestations due to the serum are
      slight and disappear promptly. The ultimate effects of the serum treatment on the
      symptoms and final outcome of the disease have still to be determined.

PMID- 19868057
TI  - EXPERIMENTAL OBSERVATIONS ON THE PATHOGENESIS OF GALL-BLADDER INFECTIONS IN
      TYPHOID, CHOLERA, AND DYSENTERY.
AB  - 1. The theory of the production of gall-bladder lesions in typhoid, by descending
      infection of the bile from the liver receives support from investigations with
      the common duct fistula method in the rabbit. More bacilli appear in the bile
      with increased doses and more gall-bladder infections are obtained by increased
      doses. More bacilli appear in the bile after mesenteric vein injection than after
      ear vein injection and more lesions result under the first condition. More
      bacilli appear in the bile after injection of the same dose in immunized animals
      than in normal animals and more lesions also result in immunized animals. In
      cholera and dysentery the same mechanism is suggested with the additional factor
      of a portal system septicemia. 2. After the appearance of microorganisms in
      rabbit bile, their fate is apparently largely determined by the antiseptic
      properties of the bile. 100 per cent infections cannot be secured by intravenous
      doses large enough to insure the presence of microorganisms in the bile. Rabbit
      bile in vitro may be antiseptic to the microorganisms considered. The antiseptic
      action is largely due to its alkalinity. It is apparently possible to protect the
      rabbit to some degree against gall-bladder infection by a previous injection of
      sodium bicarbonate. 3. Alkaline therapy is suggested in the prevention and cure
      of gall-bladder carriers.

PMID- 19868058
TI  - STUDIES ON THE BLOOD PROTEINS : I. THE SERUM GLOBULINS IN BACTERIAL INFECTION AND
      IMMUNITY.
AB  - The progress of an infection is usually associated with marked changes in the
      serum proteins. There may be an increase in the percentage of the total protein
      during some stage of the infection, and there is usually a change in the albumin
      globulin ratio with an increase in the total globulins. This rise may antedate
      the development of any resistance by a considerable period of time. The non
      protein constituents of the blood show fluctuations with a tendency to rise as
      the infection progresses. The process of immunization is in almost all instances
      associated with a definite increase in the globulins of the blood, and in some
      cases with a complete inversion of the normal albumin-globulin ratio. This may be
      produced both by living and dead organisms and by bacterial endotoxins. Massive
      doses usually result in an upset which shows no tendency to right itself during
      the period of observation. A rise in the globulins has been shown to occur long
      before the animal develops immune bodies in any appreciable concentration; and
      where the globulin curve and antibody curve appear to parallel one another, it
      can be shown by a careful analysis of both curves that there is a definite lack
      of correspondence at various periods of the experiment. Animals possessing a
      basic immunity show a more rapid rise in the globulin curve following
      inoculation. There is no parallelism between the leukocytic reaction and the
      globulin reaction. During periods of leukopenia the globulins may be as high as
      during the period of a leukocytosis. Bacterial endotoxins produce as striking an
      increase in the serum globulins as do living and killed bacteria. This would seem
      to indicate that a bacterial invasion of the organism is not absolutely essential
      for the globulin changes, and that the toxogenic factor in infection and immunity
      must play a part in the production of the changes noted. Inflammatory irritants
      injected intraperitoneally also result in a globulin increase. In this case the
      changes produced may best be explained by the toxogenic effect produced by the
      protein split products resulting from the inflammatory condition. Intraperitoneal
      injections of killed bacteria give rise to a more rapid increase in the serum
      globulins. The rapidity of the response following intraperitoneal as compared
      with intravenous injections doubtless stands in intimate relationship to the
      neutralizing power possessed by the blood serum and perhaps to the more extensive
      surface of absorption following injection by the intraperitoneal route.

PMID- 19868059
TI  - THE RELATION BETWEEN THE THYROID AND PARATHYROID GLANDS.
AB  - The following conclusions may be drawn from the experiments presented in this
      article. 1. Excessive meat diet develops hypertrophy of the thyroid gland. A
      definite hypertrophy of the parathyroid gland under the same conditions has not
      been established. A meat diet does not develop hypertrophy of the thyroid gland
      when insufficiency of the parathyroid gland exists at the same time, even if no
      clinical symptoms are present. Where a pronounced hypertrophy caused by a meat
      diet has already developed, the hypertrophy disappears and the gland assumes its
      ordinary appearance after extirpation of a sufficiently large number of
      parathyroid glands. 2. After parathyroidectomy no hypertrophy of the thyroid
      gland takes place. In chronic tetany the thyroid gland seems, on the contrary, to
      atrophy in spite of a meat diet. 3. After complete extirpation of the thyroid
      gland, the parathyroid gland does not change its structure, even in cases where
      the cachexia lasts for several years. Small remaining parts of the thyroid gland
      may through hypertrophy develop into compact tissue and thereby seemingly present
      some points of resemblance to the parathyroid gland. 4. When the parathyroid
      gland hypertrophies, as in some forms of chronic tetany, this hypertrophy is
      characterized by the development of large, transparent, sharply defined cells,
      with large nuclei rich in chromatin. 5. The parathyroid and thyroid glands are
      independent organs, each having specific functions. This, however, does not
      exclude the occurrence of a direct or indirect interaction in the functions of
      the two systems. 6. There is reason to believe that an insufficiency of the
      parathyroid gland checks to some extent the function of the thyroid gland. No
      proof of the existence of a vicarious cooperation between the two glands has been
      established.

PMID- 19868060
TI  - STUDIES ON TREPONEMA PALLIDUM AND SYPHILIS : V. FURTHER STUDIES ON THE RELATION
      OF CULTURE PALLIDA TO VIRULENT PALLIDA AND ON REINFECTION PHENOMENA.
AB  - 1. Immune sera produced in rabbits by treatment with our Culture Strain A of
      Treponema pallidum agglutinated not only the homologous strain, but also the
      Noguchi strains, and indicate a close group relationship of other non-pathogenic
      treponemata. Absorption experiments confirmed this, indicating a close
      relationship between the pallidum and the calligyrum. 2. Culture treponemata are
      not agglutinated to a much greater extent by the sera of syphilitic rabbits than
      they are by those of normal rabbits. 3. Culture treponemata are not agglutinated
      to any considerable extent by the sera of rabbits immunized with virulent
      treponemata. 4. The sera of syphilitic patients, especially those in the tertiary
      stages, agglutinate culture pallidum to a slightly greater extent than do those
      of normal individuals, but the culture pallidum is agglutinated to an almost
      equal degree by the sera of many individuals with diseases other than syphilis.
      We do not think that we could definitely distinguish the syphilitic from the non
      syphilitic serum by the agglutination of the culture pallida, and therefore we do
      not believe that the reaction has any diagnostic value at present. 5.
      Immunization with culture pallidum, either general or local, does not seem to
      confer upon rabbits any considerable degree of resistance to inoculation with
      virulent treponemata. 6. Rabbits that have once exhibited lesions in the testis
      are not easily reinfected at the same site if reinoculation is practiced more
      than a month or so after apparent healing of the lesion. We believe that the
      experiments above recorded strongly suggest that resistance to syphilis in
      rabbits is a localized cell phenomenon not dependent upon a generalized reaction
      on the part of tissues remote from the site directly involved in reaction with
      the invading treponemata. Antibodies analogous to those formed in most bacterial
      infections appear in the general circulation in slight amount, if at all. The
      finding of many motionless treponemata in a few of the small lesions following
      reinoculation suggests the possibility of a purely localized formation of
      antibodies. This was expressed by Landsteiner some years ago when he spoke of the
      localized formation of agglutinins when they were absent in the general
      circulation. We hesitate to apply these results too generally to the conditions
      prevailing in human syphilis, but they contain the possibility of an explanation
      for the apparent skin immunity of the secondary period, and the later successive
      involvement of some organs and tissues when others remain normal and when
      external superinfection is successfully resisted.

PMID- 19868061
TI  - THE RESPIRATORY MECHANISM IN PNEUMONIA.
AB  - 1. The reaction of the respiratory mechanism to carbon dioxide is greatly
      diminished in pneumonia. 2. The graver the disease, the less the reaction.

PMID- 19868062
TI  - THE INFLUENCE OF THE VAGUS NERVES UPON CONDUCTION BETWEEN AURICLES AND VENTRICLES
      IN THE DOG DURING AURICULAR FIBRILLATION.
AB  - The experiments that have been reported indicate that stimulation of either the
      right vagus or the left vagus nerve is equally effectual in blocking impulses
      from the auricles to the ventricles when auricular fibrillation is present.
      Stimulation of the left vagus nerve is as effectual in blocking impulses from the
      normally beating auricles as from the auricles when in a state of fibrillation,
      and the type of auricular activity has apparently no influence on the effect
      which stimulation of the left vagus has on auriculoventricular conduction.

PMID- 19868063
TI  - THE INTERRELATION OF THE SURVIVING HEART AND PANCREAS OF THE DOG IN SUGAR
      METABOLISM.
AB  - The experiments indicate that the pancreas, when perfused aseptically with
      Locke's solution containing physiological concentrations of dextrose, does not
      alter the reducing properties of the perfused solution. The pancreas, however,
      seems to supply something to the Locke's solution circulating through its
      arteries which in some way brings about a utilization of sugar by the living
      heart to an extent that does not occur with the heart alone. This pancreatic
      substance possesses some of the characteristics of an enzyme. It is inactivated
      by boiling; it is unstable, rapidly becoming inactive on standing; it acts in
      small amounts; it causes a great acceleration in the rate of a reaction which
      otherwise proceeds slowly, and the rate of reaction diminishes as the reaction
      proceeds. Thus this substance has more of the characteristics of an enzyme than
      of a stable internal secretion like that of the adrenal glands. The disappearance
      of sugar was dependent upon the presence of living heart tissue, and it ceased as
      soon as the perfusate was removed from the heart-pancreas circulation and did not
      occur at all when a pancreatic perfusate was passed through a non-beating heart.
      This result indicates that the reaction is not similar to that obtained when
      muscle and pancreas extracts act on more concentrated solutions of dextrose. The
      living heart in the presence of the pancreatic factor and dextrose, is
      responsible for two effects. First, a condensation of the sugar to a non-reducing
      form that yields again a simple sugar on hydrolysis or by simply standing, with a
      preservative, at 37 degrees C. for 24 hours. Second, a disappearance of sugar
      which is probably due to its destruction by hydrolysis or oxidation. After
      deducting the reducing sugar in the heart-pancreas perfusions which could be
      recovered by hydrolysis, the amount of sugar which had actually disappeared
      exceeded that which was used by the heart when perfused with dextrose alone. As
      to the fate of this portion of the sugar, no definite evidence was obtained. The
      question arises as to whether this substance obtained from the perfused pancreas
      is identical with the hypothetical internal secretion of the pancreas so
      essential in sugar metabolism. That there is an internal secretion of the
      pancreas which can be obtained by this method, and that in some way it
      accelerates the utilization of sugar by the living heart, seems evident. Though
      the conclusions are based on the heart and pancreas isolated from the numerous
      interrelating factors occurring in the body, the evidence suggests, at least,
      that the substance or substances obtained by perfusing the pancreas may be
      concerned in the normal activity of the pancreas upon sugar metabolism.

PMID- 19868064
TI  - A CONTRIBUTION TO THE EPIDEMIOLOGY OF LOBAR PNEUMONIA.
AB  - 1. Pneumococci of Type I and Type II are responsible for the majority of the
      cases of lobar pneumonia. 2. Among the pneumococci found in the mouths of healthy
      individuals, Type IV predominates, Type III is fairly frequent, and atypical
      organisms of Type II are occasionally encountered. Organisms of these types give
      rise to a minority of cases of lobar pneumonia. 3. Healthy persons intimately
      associated with cases of lobar pneumonia may harbor in their mouth secretions the
      highly parasitic pneumococci of Types I and II. 4. Occasionally a carrier of Type
      I or Type II pneumococcus is encountered in whom it is impossible to trace any
      contact with an infected patient. 5. Convalescents from lobar pneumonia may carry
      for a considerable period of time the type of pneumococcus with which they were
      infected.

PMID- 19868065
TI  - THE VARIOUS FACTORS OF RESPIRATION IN PERSONS WITH PNEUMOTHORAX.
AB  - It may be said that at rest all the factors of respiration, gaseous exchange,
      carbon dioxide tension, and the mechanical factors, are normal in persons with a
      collapsed lung, that the reaction to carbon dioxide is normal up to the point at
      which the respiration is trebled, or sometimes quadrupled, but that beyond that
      point a limit may be reached. The ventilation of the lungs can be accomplished in
      an entirely normal manner in spite of a greatly reduced vital capacity. The only
      difference between normal persons and persons with a collapsed lung is that the
      latter when called upon to increase their ventilation reach their limit a little
      sooner than the former. From these findings we might deduce that there will be no
      dyspnea except after moderate exertion. And this deduction is borne out by the
      histories of the patients. In other words, in the lungs, as in other organs,
      there is a large factor of safety, one lung being as efficient as two, except
      when the work done calls for more than a threefold increase in the normal
      ventilation.

PMID- 19868066
TI  - THE COMPARATIVE RESISTANCE OF BACTERIA AND HUMAN TISSUE CELLS TO CERTAIN COMMON
      ANTISEPTICS.
AB  - The comparative resistance of bacteria and human tissue cells to antiseptics and
      other chemicals may be easily tested by tissue cultures under conditions which
      approximate those found in the living body. A comparative study shows that while
      human cells (connective tissue and wandering cells) are highly resistant to many
      antiseptics, they are in general more easily killed than bacteria (Staphylococcus
      aureus). Of the antiseptics tested, which include mercuric chloride, iodine,
      potassium mercuric iodide, phenol, tricresol, hydrogen peroxide, hypochlorites
      (Dakin's solution), argyrol, and alcohol, the one which approaches most closely
      the ideal disinfectant is iodine, which kills bacteria in strengths that do not
      seriously injure connective tissue cells or wandering cells.

PMID- 19868067
TI  - CHANGES IN PIGMENT EPITHELIUM CELLS AND IRIS PIGMENT CELLS OF RANA PIPIENS
      INDUCED BY CHANGES IN ENVIRONMENTAL CONDITIONS.
AB  - 1. Retina pigment epithelium cells and iris pigment cells are placed in an
      identical medium. 2. The differentiation into two different parts, as well as the
      pigment strains of the migrating pigment epithelium cells, is lost. The normally
      highly specialized cuticular structures disappear. The cells begin to move and
      assume a spindle shape, thus losing their original hexagonal shape. 3. The
      migrating iris pigment cells begin to show a distribution of the pigment, similar
      to that exhibited by the migrating pigment epithelium cells. The cuticular
      structures of this cell type also disappear. These cells also assume the ability
      of free movement and become spindle-shaped. 4. By means of these changes both
      cell types not only become more similar to the ordinary culture cell type, but
      also in certain respects, more like each other, whereas before explantation they
      were very unlike. In order to accomplish this the pigment epithelium cells must
      change much more thoroughly than the iris pigment cells. 5. The changes,
      particularly those of the pigment epithelium cells, show a definite relation to
      the changes of external factors, as they are the expression of the transmission
      from dissimilar conditions existing on different sides of the cells into
      conditions which are uniform on all sides.

PMID- 19868068
TI  - THE SEPARATION OF SERUM INTO COAGULATIVE AND NON-COAGULATIVE FRACTIONS.
AB  - The fact that the coagulative principle is closely associated with the euglobulin
      fraction of the blood is of clinical as well as of theoretical interest. It
      enables us to prepare a hemostatic containing about 2 per cent of protein which
      is more potent than the whole serum containing 6 to 7 per cent of protein. A
      preparation of this kind has been made in this laboratory from horse serum and
      employed during the past few months in numerous cases of bleeding. This
      euglobulin is absolutely sterile, as it has been passed through a Berkefeld
      filter, and is safeguarded against decomposition by the addition of 0.3 per cent
      tricresol. A detailed account of the therapeutic use of euglobulin will be
      reported elsewhere. It may be stated, however, that it has been employed in the
      various manifestations of intractable hemorrhage in which horse serum has been so
      largely resorted to of late years, and that in certain cases has seemed to bring
      about most satisfactory results; in no instance has there been any untoward
      effect. When intravenous injections are resorted to, euglobulin seems to be
      preferable to serum which contains fully three times the quantity of protein. It
      also seems to be absorbed more quickly from the subcutaneous tissues. In all
      probability it will be found to meet the same indications as whole serum,
      possessing the advantages of concentration, and necessitating the introduction
      into the body of a much smaller amount of foreign protein.

PMID- 19868069
TI  - THE INFLUENCE OF CERTAIN FACTORS, ESPECIALLY EMOTIONAL DISTURBANCES, ON THE
      EPINEPHRIN CONTENT OF THE ADRENALS.
AB  - 1. No evidence has been obtained that in cats and dogs with the nerves of one
      adrenal cut, emotional disturbances cause depletion of the epinephrin store of
      the normally innervated adrenal as compared with its fellow. 2. The depletion of
      the epinephrin store in cats under morphine is not dependent upon so called
      morphine fright, since a similar depletion is found in dogs in which, as is
      known, morphine produces symptoms the reverse of those of fright. 3. The signs of
      morphine fright can all be elicited by administering morphine to a cat in which
      one adrenal has been removed and the nerve supply of the other cut, and in which
      accordingly no detectable liberation of epinephrin takes place. 4. The reactions
      of the denervated iris elicited by emotional disturbance, asphyxia, or
      etherization in a cat, one of whose adrenals has been removed and the nerves of
      the other cut, do not differ from these reactions in cats whose adrenals have not
      been interfered with. 5. The influence of postoperative edema of the adrenal in
      diminishing the epinephrin load, and the recuperation of the load after a time,
      have been studied in rabbits. 6. The diminution in the epinephrin store of the
      adrenals which follows operations on animals (postoperative depletion) has been
      studied. It is only in part associated with the anesthesia, since it may be as
      marked 6 or 8 hours after an operation lasting less than 1 hour as after 6 or 8
      hours' anesthesia without operation. 7. One adrenal was removed in rabbits and
      the epinephrin content of the remaining gland assayed at varying periods of time
      after removal of the first, the periods being longer than the time necessary for
      recovery from the postoperative depletion. In general, the second adrenal
      contained more epinephrin than the first, sometimes double the amount. 8. Marked
      depletion of the epinephrin store of innervated adrenals as compared with the
      corresponding denervated glands was seen in animals dead of infections of various
      kinds. 9. As shown by Elliott, diminution of the stock of epinephrin in the
      adrenal through electrical stimulation of the splanchnics is not easy to
      demonstrate, despite the fact that the liberation of epinephrin into the blood is
      notably increased by the stimulation. With short periods of stimulation, however,
      repeated over a long time at intervals just long enough to prevent fatigue, it
      has proved possible to demonstrate a distinct depletion.

PMID- 19868070
TI  - A STUDY OF EXPERIMENTAL NON-HEMOLYTIC STREPTOCOCCUS LESIONS IN VITALLY STAINED
      RABBITS.
AB  - 1. Repeated injections into rabbits of non-hemolytic streptococci isolated from
      human cases of infectious endocarditis or rheumatic fever will produce an acute
      arthritis in the rabbit similar in most respects to the arthritis of acute
      rheumatism. 2. Microscopical sections of the joints show a gradual transition
      from an acute exudative inflammation to advanced organization. 3. Endocarditis
      and pericarditis occur in a small percentage of cases, and focal lesions in the
      myocardium consisting of necrosis and the infiltration of cells are frequent.
      These focal lesions differ considerably from Aschoff's submiliary nodules. 4.
      Lesions in the kidneys and liver occur but are not characteristic. 5. By means of
      the vital stain it has been shown that the large endothelioid cells which play a
      prominent part in the joint and myocardial lesions belong to the group of so
      called macrophages or wandering cells and probably develop from the vascular
      endothelium.

PMID- 19868071
TI  - THE DETAILS OF THE PHOTOGRAPHICALLY RECORDED VENOUS PULSE IN AURICULAR
      FIBRILLATION.
AB  - While auricular fibrillation is easily recognized by arterial and jugular
      tracings or by electrocardiograms, it is not possible to interpret all the waves
      found in these records. The venous tracings may in general be placed in one of
      two classes: (a) those in which prominent systolic waves predominate or occur
      alone; and (b) those in which large or small diastolic waves occur occasionally,
      in groups, or in a continued series averaging 250 to 500 per minute. The
      prominent systolic waves have generally been attributed to tricuspid
      regurgitation, the inference being that tricuspid regurgitation is a common state
      in auricular fibrillation. The diastolic waves are so numerous and so many
      electrocardiograms show diastolic waves that it is impossible to account for them
      on the assumption that the auricle is in a dilated and finely fibrillating state.
      It has been suggested that in these instances a condition of coarse fibrillation,
      which is closely allied to auricular flutter, obtains. The systolic and diastolic
      waves of the venous pulse of twenty-five clinical cases of auricular
      fibrillation, recorded by photographic methods, were studied. Six types of
      systolic waves (Text-Fig. 1) were found: (1) an intensified impact wave, the most
      common and often the only characteristic feature, indicating vigorous ventricular
      action; (2) a peaked impact followed by a rapid systolic drop due to light
      pressure of the tambour; (3) the intra-auricular type of systolic variation, so
      called from its resemblance to intra-auricular pressure curves found in animals,
      occurring in clinical cases only when ventricular systole is weak; (4) double
      systolic waves, attributed to a systolic tug of the ventricle on the auricles and
      large veins; (5) a systolic impact followed by a stasis wave, present when
      intravenous pressure is high; (6) a regurgitation wave composed of a steep rise
      continued into a systolic plateau with murmur vibrations superimposed. Our study
      showed (1) that tricuspid regurgitation, as indicated by the presence of
      regurgitation waves, is a rare accompaniment of auricular fibrillation; and (2)
      that the contrary opinion, arrived at by the frequent presence in polygraph
      tracings of ventricular types of waves, is due to the fact that the contour of
      intensified impact waves is distorted by polygraph levers so that they simulate
      regurgitation waves. Recurrent diastolic waves were frequently present in our
      records. Their relative size depended, to a considerable extent, on the pressure
      of the tambour. There was no constant relation to similar waves in the recorded
      electrocardiogram, nor is it proven that they are indicative of a coarse type of
      fibrillation or an associated flutter.

PMID- 19868072
TI  - THE PRODUCTION OF ARTERIOSCLEROSIS AND GLOMERULONEPHRITIS IN THE RABBIT BY
      INTRAVENOUS INJECTIONS OF DIPHTHERIA TOXIN.
AB  - There may be produced in rabbits by the intravenous injection of large doses of
      diphtheria toxin a vascular degeneration involving the entire aorta, the carotids
      to the base of the skull, the subclavians, and iliacs, and, for a varying
      distance distally, the brachials, femorals, and large abdominal vessels. The
      first part of the pulmonary artery is sometimes affected. The lesion is
      practically diffuse throughout the aorta and vessels mentioned, consisting of a
      fatty degeneration and necrosis of the smooth muscle in a wide zone of the media
      and a crowding together of the elastic fibers in the region affected, resulting
      in an irregular thinning of the vessel walls and many small aneurysmal pouchings.
      In rabbits which received pituitrin with the diphtheria toxin extensive
      calcification occurred throughout this degenerated zone, both in the aorta and
      other large vessels. It is believed, however, that pituitrin is not essential to
      the calcification and that if it is of any importance it is because an extreme
      fatty degeneration is produced more quickly in the media of the vessels when it
      is administered simultaneously with the toxin. Diphtheria toxin, given in large
      doses intravenously, produces in the kidneys of the rabbit a pronounced vascular
      and parenchymatous degeneration. The former consists of a swelling and
      desquamation of the endothelial cells of the arterioles and small veins with the
      formation of fibrinous thrombi, a necrosis and thrombosis of the capillaries of
      the tufts with hemorrhage and the formation of fibrinous and hyaline masses, and
      in some of the affected glomeruli considerable collections of polymorphonuclear
      leukocytes.

PMID- 19868073
TI  - EXTIRPATION OF THE THYMUS IN THE GUINEA PIG.
AB  - 1. Accessory lobes of thymus, derived from the third pharyngeal pouch, occurring
      in close association with the parathyroids from the third pouch, were found in
      serial section of the cervical tissues of eleven out of fourteen guinea pigs, and
      probably would have been found in all fourteen but for a technical error. 2. It
      is probable, therefore, that accessory lobes of thymus having this situation and
      origin are usually, if not always, present in the guinea pig. 3. Additional
      accessory lobes of thymus belonging to, but at some distance from the main lobe
      were also present in several of the animals. 4. The discovery of these accessory
      lobes makes it certain that the guinea pig is unsuitable material for complete
      thymectomy, and probably complete extirpation of the thymus in this animal is
      rarely, if ever accomplished. 5. The extirpation experiments of previous
      investigators in the guinea pig must now be regarded as partial extirpations, and
      their results interpreted in that light. 6. Extirpation of the thymus in the
      guinea pig produced no changes in the writer's experiments. 7. The study of the
      serial sections of the cervical tissues of the guinea pig indicates that Ruben's
      statements regarding the parathyroid derived from the fourth pharyngeal pouch in
      the guinea pig are correct,-that it is much smaller than parathyroid III, may be
      rudimentary, and is sometimes absent at least on one side. 8. No accessory lobe
      of thymus was found accompanying the parathyroid from the fourth pouch, a finding
      also bearing out Ruben's statement that no thymus anlarge springs from the fourth
      pouch in the guinea pig.

PMID- 19868074
TI  - EXPERIMENTAL STUDIES ON THE RELATION OF THE PITUITARY BODY TO RENAL FUNCTION.
AB  - 1. The inconstant results of past observations on the relation of pituitary
      extracts to renal activity have been due chiefly to unsuitable methods. 2. A
      standard curve of artificially induced polyuria may be plotted for rabbits,
      giving 200 cc. of water by mouth. 3. Extracts of the pars intermedia and
      posterior lobe of the hypophysis, given by mouth, subcutaneously, or
      intravenously, are able definitely to check polyuria thus induced. Extracts of
      the anterior lobe show a similar effect, but only to a slight degree. 4. This
      antidiuretic effect is constant, and is independent of (a) changes in blood
      pressure, (b) intestinal absorption, and (c) the vagi. The effect is apparently
      prevented or delayed by division of the splanchnics, and is diminished by
      division of the renal nerves near the hilus. 5. A similar antidiuretic property
      is possessed: (a) by beta-imidazolylethylamine, (b) by p-oxyphenylethylamine, (c)
      by a preparation from Secale cornutum, (d) by small doses of nicotine, (e) by
      large doses of caffeine, and (f) by extracts of the adrenal cortex. 6. No effect
      on the polyuria is produced: (a) by strychnine (b) by morphine, (c) by adrenalin,
      or by extracts of (d) thyroid, (e) thymus, (f) pineal, (g) pancreas, or (h)
      corpora lutea. 7. In animals under chloral or paraldehyde anesthesia a short and
      inconstant initial increase in flow of urine is seen. 8. The antidiuretic effect
      is absent or only slightly marked in checking the so called salt diuresis.

PMID- 19868075
TI  - THE PHAGOCYTIC POWER OF CONNECTIVE TISSUE CELLS.
AB  - By the tryptic digestion of cultures in vitro of avian and mammalian connective
      tissue, suspensions of individual, living cells have been obtained. Their ability
      to phagocyte carmine and bacteria has been tested. The great majority of them
      fail to take up either, but a few large cells are able to do so. They will ingest
      bacteria only when serum is present; that is, they require the interaction of
      opsonins. There is good reason to suppose that the phagocytic cells are
      endothelial in nature. Should they prove to be fibroblasts, like the other
      elements present, the fact will remain that the phagocytic power of fibroblasts
      is practically negligible. Their failure to ingest foreign matter in vivo is to
      be laid not to the obstacles offered by the solidity of the tissue they compose,
      but to an inherent lack of ability on their part. The phagocytosis of blood
      pigment, bacteria, etc., which takes place in granulation tissue in vivo is
      probably carried on wholly by endothelial cells and wandering cells.

PMID- 19868076
TI  - THE SIGNIFICANCE OF THE DIASTOLIC WAVES OF THE VENOUS PULSE IN AURICULAR
      FIBRILLATION.
AB  - With the clinical recognition, that different degrees of fibrillation occur and
      that these in turn are closely related to a coordinated type of auricular
      tachyrhythmia (flutter); further, that one type may lapse into another or into a
      perfectly normal rhythm, the conviction has grown that finer and coarser types of
      auricular movement may be recognized by the amplitude of the diastolic waves of
      the electrocardiogram and venous pulse. The present investigation into the cause
      of these waves has shown that this is not possible. There is no theoretical or
      experimental reason for the assumption that any fixed relation exists between the
      amplitude of the electrical variations of the electrocardiogram, which are the
      resultant of variations accompanying the irregularly spreading excitation wave,
      and the degree of mass contraction following. The large recurrent waves of the
      venous pulse, which may with more reason be regarded as related to the size of
      the auricular mechanical contractions on theoretical grounds, are also shown to
      be without differential value. The reasons for this may be briefly summarized. In
      the first place, the presence of diastolic waves is contingent upon a slow heart
      rate and long ventricular diastoles. With rapid heart rate their occurrence is
      prevented by the closely placed systolic variations. It is therefore conceivable
      that both coarse and fine fibrillation as well as flutter will be without
      diastolic waves as long as the heart is rapid. Even in the cases with long beats
      present their significance must remain doubtful. It is true that in the
      experiments the waves accompanying coarse fibrillation are as a rule somewhat
      larger than those occurring during fine fibrillation; waves of considerable size
      may, however, be present in fine fibrillation. Hence, as long as no calibrated
      method of recording is possible, it is difficult to draw any inference. It is
      possible from the same patient to record with the same apparatus diastolic waves
      of varying amplitude by merely changing the pressure of the receiving tambour.
      The chief reason that the amplitude of these waves cannot be regarded as of
      differential value is found in their origin. Fine fibrillating movements of the
      auricle do not in themselves produce waves in the jugular. They produce neither
      pressure variations in the auricle, nor exert any traction upon the veins. The
      only factor capable of producing jugular waves during fine fibrillation seems to
      be the traction exerted by the position changes of the ventricle on the auricle
      and large veins. This may, in a measure, explain why the diastolic waves recorded
      from the apex and second left interspace of patients often closely correspond
      with those simultaneously recorded from the jugular. The term "fibrillary waves"
      commonly applied to the smaller of these variations is evidently poorly chosen
      when their etiology is considered. The coarser contractions of the auricle during
      coarse fibrillation also produce no pressure changes within the auricle. They are
      vigorous enough at times, however, to exert a traction upon the venous walls.
      Hence, the waves during coarse fibrillation may be regarded as partly of
      ventricular and partly of auricular origin, or, as is frequently the case, as due
      to an interference of the two tractions. It is owing to their dual origin that
      they are more numerous and distinct when recorded from the same animal without
      changing the position or pressure of the receiving apparatus.

PMID- 19868077
TI  - SPIROCHAETA MORSUS MURIS, N.SP., THE CAUSE OF RAT-BITE FEVER : SECOND PAPER.
AB  - 1. Since our first report on the discovery of the cause of rat-bite fever, we
      have been able to prove the existence of the same spirochete in five out of six
      more cases which have come under our observation. 2. The clinical symptoms of rat
      bite fever are inflammation of the bitten parts, paroxysms of fever of the
      relapsing type, swelling of the lymph glands, and eruption of the skin, all
      occurring after an incubation period usually of from 10 to 22 days, or longer. 3.
      Our spirochete is present in the swollen local lesion of the skin and the
      enlarged lymph glands. But as the spirochetes are so few in number it is
      exceedingly difficult to discover them directly in material taken from patients.
      It is therefore better to inoculate the material into a mouse. In some cases the
      organism is found in the blood of the inoculated animal after a lapse of 5 to 14
      days, or at the latest 4 weeks. 4. Generally speaking, the spirochetes present
      thick and short forms of about 2 to 5 micro and have flagella at both ends.
      Including the flagella, they measure 6 to 10 micro in length. Some forms in the
      cultures reach 12 to 19 micro excluding the flagella. The curves are regular, and
      the majority have one curve in 1 micro. Smaller ones are found in the blood and
      larger ones in the tissues. 5. The spirochetes stain easily. With Giemsa's stain
      they take a deep violet-red; they also stain with ordinary aniline dyes. The
      flagella, too, take Giemsa's stain. 6. The movements of our spirochetes are very
      rapid, resembling those of a vibrio, and distinguish them from all other kinds of
      spirochetes. When, however, the movements become a little sluggish, they begin to
      present movements characteristic of ordinary spirochetes. 7. For experimental
      purposes, mice, house rats, white rats, and monkeys are the most suitable
      animals. Monkeys have intermittent fever after infection, and spirochetes can be
      found in their blood, but they are not so numerous as in the blood of mice. Mice
      are the most suitable animals for these experiments, and they appear, as a rule,
      to escape fatal consequences. 8. The spirochete is markedly affected by
      salvarsan. 9. The organism is not present in the blood of all rats, and there is
      no relation between the species of the rat and the ratio of infection. We have
      never found the spirochete in healthy guinea pigs or mice. By permitting a rat
      infected with the spirochete to bite a guinea pig, the latter develops the
      disease. 10. We have succeeded in cultivating the spirochete in Shimamine's
      medium. 11. Among the spirochetes described in the literature or discovered in
      the blood of rats and mice, there may be some resembling our spirochete, but none
      of the descriptions agree with it fully. Hence we have named our organism
      Spirochaeta morsus muris and regard it as belonging to the Spironemacea (Gross)
      of the nature of treponema. 12. The spirochete can be detected in the bodies of
      patients. In seven cases out of eight, it disappears on recovery, only to
      reappear during the relapse. 13. The spirochete can be detected in about 3 per
      cent of house rats. These facts enable us to identify the cause of the disease.
      14. There may be other causes than the spirochete for diseases following the bite
      of a rat. The cause, however, of rat-bite fever in the form most common in Japan
      is, we believe, the spirochete which we have described.

PMID- 19868078
TI  - EXPERIMENTAL RAT-BITE FEVER : FIRST REPORT.
AB  - 1. We have confirmed Ogata's results in experimental rat-bite fever caused by the
      bite of rats. 2. In our experiments with guinea pigs, swelling and congestion of
      the bitten parts, swelling of the subcutaneous lymph nodes, fever, and loss of
      weight were the typical symptoms. The progress of the fever was not so regular as
      in human cases, but we find records in the literature of patients who showed
      irregular fever types or were afebrile. The chief points that we noted in the
      anatomical view of the guinea pigs were swelling and congestion of the lymph
      gland system and acute changes in the adrenals and kidneys. 3. If an emulsion
      made from the lymph glands, cerebral substance, or the adrenals, or the heart's
      blood of a guinea pig of the original generation is inoculated subcutaneously or
      intraperitoneally into a fresh guinea pig, the animal invariably dies with the
      usual symptoms of fever and swelling of the lymph glands. The anatomical changes
      in this case were the same as those of the original guinea pig, except that the
      course was shorter and more regular. The same result was observed in further
      generations. No change was observed in pathogenicity, and in the guinea pigs of
      the original and further generations a species of spirochete as the causative
      agent was always observed. The incubation period in the original generation was
      from 1 to 2 weeks, and in further generations about 1 week. 4. When a mouse or
      white rat was inoculated, spirochetes always appeared in the peripheral blood,
      but no other symptoms developed. When peripheral blood drawn from a mouse thus
      treated was inoculated into a fresh mouse or a fresh white rat and peripheral
      blood drawn from the mouse and rat was inoculated into a fresh guinea pig, they
      all became infected and the guinea pigs always died. Thus we found that rats and
      mice are media but not victims of the disease, while guinea pigs are both media
      and victims of it. 5. In the rhesus monkey on which we made our experiment we
      witnessed a process similar to that of human rat-bite fever, and our spirochotes
      were observed in other animals into which blood drawn from the monkey was
      inoculated. 6. In the original animals spirochetes were seen chiefly toward the
      end of the process and the conditions as to the period previous to it are not yet
      clearly known. In further generations of all the animals we used, spirochetes
      were found in the peripheral blood 4 or 5 days after inoculation, and gradually
      multiplied until the greates number was reached about the 10th day after
      inoculation. They then began to decrease; yet spirochetes could be observed over
      2 months later. 7. We have found spirochetes chiefly in the adrenals of the
      animals by Levaditi's method, but have not yet ascertained their distribution in
      other organs. 8. Our spirochete is short, round, and highly motile; it stains
      readily, and has few spirals. We have not yet observed an undulating membrane,
      but have seen what we believe to be flagellum at each end. 9. The identification
      of our spirochete with other species must be left for further study. The
      spirochete which Futaki, Takaki, Taniguchi, and Osumi found in two patients with
      rat-bite fever, seems to differ from ours in form. 10. Spirochetes disappear from
      the blood of the animals as a result of the injection of salvarsan, thus
      indicating that the spirochete is arsentropic.

PMID- 19868080
TI  - THE CONTROL OF STRYCHNINE CONVULSIONS BY INTRASPINAL INJECTIONS OF MAGNESIUM
      SULPHATE.
AB  - We feel that the results obtained in the human case and in our animal experiments
      justify the supposition that magnesium sulphate may be of use in controlling
      cases of poisoning by strychnine. It is a method easily available not only in
      large hospitals but in private practice, and requires no elaborate technique. The
      amount of magnesium sulphate to be used should follow the advice of Meltzer (19)
      in tetanus cases: intraspinally 1 cc. of a 25 per cent solution to each 20 pounds
      of body weight in adults, and one-half the dose in young children. Should this
      not control the convulsions a small amount of ether may be used. In order to
      hasten the excretion of strychnine, 200 to 300 cc. of salt solution should be
      given intravenously.(6) In the event of the return of the convulsions, the
      intraspinal dose may be repeated, always taking precautions to keep the head
      elevated. Meltzer's apparatus for intrapharyngeal insufflation and a 2.5 per cent
      solution of calcium chloride should always be on hand in case of respiratory
      failure following an overdose of the magnesium salts (Meltzer (19)).

PMID- 19868079
TI  - THE ACTION OF DIGITALIS IN PNEUMONIA.
AB  - We have shown in a series of 105 cases of pneumonia, 95 of which we have selected
      as available for statistical study, that digitalis given by mouth has an action
      on the heart. We have judged this action to be present because changes occurred
      in the auriculoventricular conduction time and in the form of the T wave of the
      electrocardiogram, just as they do in the non-febrile heart. This conclusion is
      strengthened by finding that the pulse rate in fibrillating and fluttering cases
      fell in the presence of fever, exactly as it does in non-febrile cases. The dose
      and the time required to produce these effects are given and are the same as in
      the non-febrile cases. When there was a difference in the amount necessary to
      produce one or the other of the changes, it was found that the T wave is more
      often and more readily affected than the conduction interval. We have shown that
      the intoxication due to pneumonia is probably not responsible for the changes
      found, both from a study of the statistics and because in the control cases
      reverse tendencies were often found (that is, decrease in conduction time and
      increase in the size of the T wave). We have shown that the method of selection
      in consequence of which we treated a large number of severe cases did not
      prejudice our results, because it could be demonstrated that the proximity of
      death, whether in control or treated cases, was not necessarily associated with
      the changes we are describing. We have also, by referring to the literature of
      the subject, brought evidence to show that heart muscle does not undergo those
      changes in pneumonia, as it does in other infectious diseases, which would lead
      one to expect changes in conduction found in other diseases. The changes in
      conduction which have been reported by others were almost entirely associated
      with the giving of digitalis.

PMID- 19868081
TI  - STUDIES ON THE METABOLISM OF CELLS IN VITRO : I. THE TOXICITY OFalpha-AMINO-ACIDS
      FOR EMBRYONIC CHICKEN CELLS.
AB  - Summing up these results, we found that all the ten alpha-amino-acids used
      inhibited the growth of the cells and finally killed the cultures. This
      inhibition is preceded by a short period of activity. The typical effect on the
      cells is shown in Figs. 1 and 2. The first (Fig. 1) is a control culture showing
      the usual growth of cells and their typical spindle shape form. The second (Fig.
      2) is a culture in plasma plus asparagine showing the cells rounded off and
      beginning to undergo dissolution. We do not wish to draw too extensive
      conclusions from these experiments, but we believe that toxicity of alpha-amino
      acids towards growing cells has been shown beyond a reasonable doubt; while we
      have found that compounds of higher molecular weight, namely, the peptones of egg
      yolk and proteins, are non-toxic. This toxicity depends upon the concentration
      and the time that the cells are exposed to their action. As these factors are
      reduced, the toxicity is decreased. In this respect, these substances are similar
      to all cell poisons. Applying these results to the work done on the intravenous
      injection of digestion mixtures, we believe that we have found a reason for the
      death of the experimental animals when the hydrolyzed proteins were injected too
      rapidly. Buglia found that large amounts of alpha-amino-acids could be injected
      into the circulation without causing deep-seated changes in the renal and
      intestinal functions, provided they were injected slowly enough; in fact, that
      enough of these mixtures could be injected in this way to cover the nitrogen
      consumption of the body. This injection, however, was always accompanied by an
      alpha-amino excretion through the urine and an increase of the peristalsis, of
      the intestine, with resultant liquid stools. As is well known, a sudden great
      concentration of these substances in the blood of an animal causes death. These
      results agree with our findings Folin and Denis demonstrated the fact that alpha
      amino-acids probably pass into the circulation through the intestines. Van Slyke
      and Meyer, by means of Van Slyke's nitrogen method, have practically proven this,
      and Abel, Rowntree, and Turner, and Abderhalden have lately succeeded in
      obtaining alpha-amino-acids in crystalline form from the blood. Van Slyke and
      Meyer have shown that the tissues take up alpha-amino-acids to a certain point,
      but that after this the limit of saturation is reached. This is not so in the
      liver, which continually desaturates itself by metabolizing the alpha-amino-acids
      that it has absorbed, and consequently maintains indefinitely its power of
      removing them from the circulation, as long as they enter it no faster than the
      liver can metabolize them. Marshall and Rowntree have shown that there is an
      increase of the alpha-amino-acid concentration in the blood after injuries to the
      liver, which have caused deep-seated anatomical changes. Our experiments prove
      that tissue cells in general are unable to live in the presence of any great
      concentration of these acids. At the present time we do not feel able to give an
      explanation of the significance of this evident toxicity. However, the fact in
      itself seems to indicate that we should expect stimulation from a certain
      increase of the alpha-amino-acid concentration in the body, or the concentration
      of any one of the acids, while a greater increase would lead to marked
      disturbances of the metabolism.

PMID- 19868082
TI  - VENOM HEMOLYSIS AFTER SPLENECTOMY, INCLUDING THE RESISTANCE OF THE ERYTHROCYTES
      OF NORMAL DOGS TO THE HEMOLYTIC ACTIVITY OF COBRA VENOM.
AB  - 1. The resistance of erythrocytes of dogs to the hemolytic activity of cobra
      venom is increased after splenectomy. 2. This increased resistance was observed
      as early as 4 days after splenectomy and usually persisted for a period of about
      3 weeks, when the resistance gradually decreased to normal or slightly beyond. 3.
      The decrease of resistance to the hemolytic activity of venom for the
      erythrocytes of splenectomized dogs following the primary increase is apparently
      coincident with the anemia following splenectomy. An intercurrent infection, such
      as distemper, tends to reduce the resistance of erythrocytes to venom. 4. An
      increased resistance of the erythrocytes to hypotonic salt solutions was found
      with all the splenectomized dogs in which these tests were made. Increased
      resistance to hypotonic salt solutions apparently persists for a longer period
      than the increased resistance to cobra venom. 5. As the lysis of erythrocytes by
      venom is dependent upon the presence of certain lipoidal substances within the
      cells, and as the spleen may exercise an influence over the lipoidal contents of
      corpuscles and serum, it is suggested that the increased resistance of
      erythrocytes to the hemolytic activity of venom after splenectomy is due to
      alterations in the lipoid content of the erythrocytes.

PMID- 19868083
TI  - THE EFFECTS OF SERUM TREATED WITH PARARABIN.
AB  - Horse serum, kept for 2 hours at 38 degrees C. in the presence of one-fifth its
      volume of a suspension of 0.5 per cent of pararabin inphysiological salt solution
      and then freed by means of centrifugalization and filtration from the pararabin
      produced when injected in appropriate doses into a normal rabbit, a considerable
      and prolonged fall of the blood pressure, a distinct retardation in the
      coagulation of the carotid blood, and sometimes, in addition, acceleration of the
      respiratory rate and the expulsion of numerous scybala; that is, the various
      symptoms observed to occur after the intravenous injection of horse serum in sero
      anaphylactized rabbits. If the horse serum is first heated for 30 minutes to 56
      degrees C. and then treated with pararabin in the manner described above, the
      intravenous injection of this serum into a normal rabbit exerts no more action on
      the arterial pressure, the coagulability of the arterial blood, the respiratory
      rate, and the intestinal activity, than does normal horse serum when introduced
      into the vein of a normal rabbit.

PMID- 19868084
TI  - STUDIES ON THE BLOOD PROTEINS : II. THE ALBUMIN-GLOBULIN RATIO IN EXPERIMENTAL
      INTOXICATIONS AND INFECTIONS.
AB  - The intoxication which develops as the result of a simple obstruction or a closed
      intestinal loop is accompanied by definite changes in the coagulable proteins of
      the blood serum. These changes consist essentially in an alteration in the normal
      albumin-globulin ratio; the globulin fraction is greatly increased and at times
      the normal relation of the two fractions may show a complete inversion. The
      increase in the globulin content of the blood serum is most marked in the animals
      which show some of the complications met with in loop animals,-rupture of the
      loop and peritonitis. In the latter conditions especially, the globulin increase
      is rapid and large. We believe this reaction to be of diagnostic value in acute
      infections attended by the sudden liberation and absorption of a toxic exudate.
      Infections and intoxications produced by inflammatory irritants are also
      accompanied by a rise in the blood globulins. This observation suggests that
      tissue disintegration with absorption of toxic products is responsible for the
      changes noted, and that bacterial invasion is important only in as far as it
      gives rise to toxic substances. Animals which have developed a tolerance to
      proteose intoxication following the periodic injection of small doses of proteose
      do not show a globulin increase. These experiments do not support the view that
      the rise in globulins observed in these experimental conditions is an expression
      of a resistance or tolerance developed by the animal. From the experimental
      evidence it seems more probable that the alteration in the partition of the blood
      protein fractions is one of the results of the metabolic disturbance which has
      been shown to occur in these conditions.

PMID- 19868085
TI  - ON THE NYMPH AND PROSOPON OF THE TSUTSUGAMUSHI, LEPTOTROMBIDIUM AKAMUSHI, N. SP.
      (TROMBIDIUM AKAMUSHI BRUMPT), CARRIER OF THE TSUTSUGAMUSHI DISEASE.
AB  - Nomenclature. As mentioned above, the prosopon and the nymph of the tsutsugamushi
      have many characteristics which distinguish it from the other trombidia. These
      are the pale color and small size of the body, delicacy of the skin, the
      conspicuous constriction between the cephalothoracic region and the abdomen,
      rudimentary eyes and tracheal openings, absence of tracheal capillaries, etc. The
      fact that the thumb or the appendage of the palpus does not start from the side
      of the fourth joint of the latter but from its end, is another charac teristic
      which does not occur in other trombidia. From the biological point of view two
      facts should be mentioned; i.e., the adult female does not deposit eggs in heaps,
      and in contrast to those of other species, the larvaae hatch out all through the
      year and feed on mammals. From these characteristics running through all the
      stages of development, we believe that we are justified in claiming a new genus
      for the tsutsugamushi. We therefore propose to change the scientific name given
      to this mite by Brumpt in 1910, Trombidium akamushi, and to introduce instead,
      according to the suggestion of Drs. Goto and Watase, the name Leptotrombidium
      akamushi. Determinaton of Leptotrombidium akamushi, N. Sp. Prosopon and Nymph. 1.
      Pale color. 2. Delicacy of the skin. 3. Distinct constriction between the
      cephalothoracic region and the abdomen. 4. Rudimentary, sessile eyes. 5.
      Indistinctnes of tracheal openings. 6. Absence of tracheal capillaries. 7. Crista
      abruptly widened at the end. 8. One palpal claw. Larva. 1. One scutum. 2. Round
      pinacles. 3. Legs, six joints, not counting the coxa. 4. Haris on the coza: one
      each on Joints 1, 2, and 3. 5. Hairs on the scutum, including two tactile hairs,
      seven; one is in the median line. Specific Determination of Leptotrombidium
      akamushi, N. Sp. (Trombidium akamushi Brumpt, 1910). Prosopon. 1. Small size 2.
      Three pairs of sucking discs on the external genitalia. 3. Hairs of the body
      feathered, club-shaped at the end, and the colorless. 4. The appendage of the
      palpus tapes distinctly towards the end. Nymph. 1. The size of the body is
      smaller thant that of the prosopon. 2. Two pairs of sucking discs on the external
      genitalia. There are no other distinct differences in the external morphology
      between the proposon and the nymph. Larva. 1. The color of the body is orange
      red, but becomes paler after sucking on mammals. 2. The hairs of the body average
      110 to 120 in number. 3. One pair of double eyes. 4. The sucking tube is visible
      when feeding on mammals (Hayashi). 5. The salivary gland is relatively large
      (Kawamura and Komagata). 6. The number and arrangemetn of the hairs on the legs
      and mouth parts correspond to the description given by Hirst. 7. The larvae are
      found all through the year. 8. The larva is the carrier of tsutsugamushi disease
      in man.

PMID- 19868086
TI  - IS TROMBIDIUM HOLOSERICEUM THE PARENT OF LEPTUS AUTUMNALIS?

PMID- 19868087
TI  - A CONTRIBUTION TO THE STUDY OF PANCREAS INTOXICATION.
AB  - 1. A toxic constituent is present in the fresh pancreas of dogs before
      trypsinogen can have been activated. 2. The toxic fraction is present in the beta
      nucleoprotein, and therefore is thermostable. 3. It is gradually destroyed by
      autolysis but can be obtained in concentrated form from a gland which has
      autolyzed 24 hours. 4. The toxic material is probably protein in nature. 5.
      Intravenous or intraperitoneal injection of from 0.05 to O.I gm. per kilo of body
      weight is usually fatal and elicits in dogs symptoms comparable to those of
      spontaneous hemorrhagic necrosis of the pancreas. 6. Dog pancreas differs from
      that of beef or pig in that guanylic acid and toxic protein combined with it are
      slowly broken down by autolysis. 7. After autolysis of dog pancreas the toxic
      protein and guanylic acid may be separated and obtained in relatively pure form.

PMID- 19868088
TI  - THE CYCLIC CHANGES IN THE MAMMARY GLAND UNDER NORMAL AND PATHOLOGICAL CONDITIONS
      : I. THE CHANGES IN THE NON-PREGNANT GUINEA PIG.
AB  - 1. A definite cycle exists in the mammary gland of the non-pregnant guinea pig
      which corresponds to the cycle in the ovary and uterus. This cycle can be
      presented through a curve in which the ordinates represent the degree of activity
      of the gland in a series of animals, and the abscissae the time since ovulation
      (period of sexual cycle). The curve passes through a first maximum at the time of
      heat and ovulation and gradually falls. The minimum is reached on the 6th day and
      continues until the 15th day after ovulation. Next begins the period when a new
      ovulation is imminent and the number of the proliferating glands again increases.
      We see. then that during the normal cycle the presence of well preserved,
      functioning corpora lutea does not lead to proliferation, neither do mature
      follicles have such an effect. On the other hand, the absence or degeneration of
      the corpora lutea is required to insure the proliferation of the mammary gland in
      the first period of the sexual cycle. If the sexual period is experimentally
      prolonged, we find in some instances proliferation, while in others it is absent.
      As far as we can determine at the present time, two factors seem to favor
      proliferation of the mammary gland under these conditions: (1) the presence of
      well preserved corpora lutea, particularly if they are associated with well
      preserved experimentally produced deciduornata, and (2) the imminence of a new
      period of heat. The connection between good corpora lutea and good deciduornata
      and the presence of proliferating mammary glands at this stage of the sexual
      cycle is, however, not absolute. There are cases in which a proliferating gland
      is associated with some degeneration of the corpus luteum. Or on the other hand a
      well preserved corpus luteum is associated with a non-proliferating gland. In
      some of the latter cases the simultaneous presence of a necrotic deciduorna may
      perhaps explain the lack of proliferation in the mammary gland. However, in the
      majority of cases we found the presence of good corpora lutea and good
      deciduomata associated with a proliferating mammary gland. Whether a living
      corpus luteum as such is able to produce proliferation of the gland is as yet
      doubtful. 2. Extirpation of the ovaries prevents not only the proliferation of
      the mammary gland associated with the first stage of the sexual cycle, the
      condition of heat and ovulation no longer taking place in castrated animals, but
      in all probability also inhibits the proliferation of the mammary gland which
      occurs under certain conditions towards the end of the sexual cycle, or in
      instances of experimentally prolonged sexual cycle in which well preserved
      corpora lutea and deciduornata are present. 3. In animals in which the ovaries
      were hypotypical, the mammary glands were in an inactive condition. The presence
      of hypotypical ovaries has the same influence on the mammary gland as castration.
      In the majority, but not in all of these cases well preserved corpora lutea were
      absent. 4. Complete extirpation of the corpora lutea seems directly or indirectly
      to prevent the secondary proliferation of the mammary gland, which occurs during
      the latter part of the sexual cycle or during an experimentally prolonged cycle,
      in cases in which the extirpation is not followed at once by a new ovulation.
      This conclusion we consider, however, merely as suggested, not yet as definitely
      established through our results. On the other hand, the primary proliferation of
      the mammary gland, during the first stage of the sexual cycle, as well as
      ovulation and the objective signs of heat, is accelerated through complete
      extirpation of the corpora lutea. Thus the effect of extirpation of the corpora
      lutea differs from the effect of castration, in that after the latter neither a
      new heat nor the primary proliferation of the mammary gland occurs. As one of the
      authors has pointed out previously, the absence of functioning corpora lutea and
      the presence of either well developed ovarian follicles or of mature follicles
      are necessary for the occurrence of heat and ovulation. The same conditions are
      prerequisites for the primary proliferation of the mammary gland. 5. In cases in
      which the whole or almost the whole uterus had been extirpated, the corpora lutea
      were well preserved and the mammary gland was proliferating.

PMID- 19868089
TI  - THE CYCLIC CHANGES IN THE MAMMARY GLAND UNDER NORMAL AND PATHOLOGICAL CONDITIONS
      : II. THE CHANGES IN THE PREGNANT GUINEA PIG, THE EFFECT OF LUTEIN INJECTIONS,
      AND THE CORRELATION BETWEEN THE CYCLE OF THE UTERUS AND OVARIES AND THE CYCLE OF
      THE MAMMARY GLAND.
AB  - 1. In the pregnant guinea pig proliferation of the mammary gland becomes regular
      only at a later stage of pregnancy; namely, during the period following the 24th
      day of pregnancy. Previous to this period proliferation was absent in the
      majority of cases. Proliferation of the mammary gland during pregnancy becomes
      regular only at a period of time which exceeds the duration of the normal sexual
      cycle unaccompanied by pregnancy. It is probable that pregnancy as well as the
      presence of living deciduornata and corpora lutea increases the proliferative
      activity of the mammary gland as compared with the ordinary cycle in non-pregnant
      animals or in animals lacking corpora lutea and deciduornata. 2. After the
      completion of pregnancy and in the beginning of secretion some mitotic
      proliferation may still be present, but it soon ceases, probably as the result of
      those processes that lead to secretion. While during the period of secretion,
      notwithstanding the presence of a new pregnancy, mitotic proliferation soon
      ceases, some proliferative stimulus seems still to be active, which, however,
      under existing conditions apparently leads only to a mitotic multiplication of
      nuclei. The latter conclusion is only suggested at the present time and needs
      confirmation through further studies. 3. In cases in which abortion took place in
      the first half of pregnancy secretion in the gland was not established; secretion
      occurred in two animals aborting toward the latter part of pregnancy. In one of
      these cases, mitotic proliferation of some gland cells was associated with the
      microscopic appearances of secretion. 4. In guinea pigs castrated during an early
      period of pregnancy in which pregnancy continued for some time, proliferative
      changes were absent in the mammary gland. In conjunction with a partial similar
      effect observed after extirpation of the corpora lutea during pregnancy, we may
      perhaps attribute the lack of proliferation in some of these cases to the absence
      of the ovaries. 5. Extirpation of the corpora lutea during pregnancy induces a
      new ovulation and with it the primary proliferation in the mammary gland;
      abortion does not necessarily prevent these proliferative changes. Extirpation of
      the corpora lutea during pregnancy perhaps prevents the secondary proliferative
      changes in the mammary gland. 6. Five injections of cow's lutein given in
      relatively large quantities intraperitoneally do not produce proliferation of the
      mammary gland in the guinea pig.

PMID- 19868090
TI  - A COMPARATIVE STUDY OF CERTAIN ACTIONS OF ADRENALIN IN THE CAT AND THE RABBIT.
AB  - The present investigation brought out the facts that the pupil of the cat is
      little affected by instillation of adrenalin, but shows, nevertheless, a greater
      responsiveness to adrenalin when given intravenously than does that of the
      rabbit, and that the duration of the dilatation effected by intravenous injection
      is, on the contrary, longer in the rabbit. In regard to the vasoconstricting
      effect of adrenalin when administered intravenously, it was found that the
      intensity as well as the duration of the rise of blood pressure was greater in
      the rabbit than in the cat.

PMID- 19868091
TI  - THE SIGNIFICANCE OF THE EPITHELIAL CELLS AND SAPROPHYTES IN SPUTUM.
AB  - 1. Microscopical examination of sputum that has been washed with isotonic salt
      solution indicates its source. Sputum from above the vocal cords contains
      polygonal flat epithelial cells and numerous species of non-pathogenic
      microorganisms. Sputum from below the cords is clear of saprophytes, although it
      sometimes contains bronchoalveolar cuboidal cells. 2. The source of the sputum
      can be determined by the erythrocytes and the bacilli that are contained in it,
      and the site of the lesion can also be ascertained. 3. In every instance I found
      erythrocytes in the pulmonary sputum after severe pulmonary hemorrhage. 4. Six of
      the cases of laryngeal affection referred to in the presentpaper had had no
      subjective symptoms, but microscopical examination showed tubercle bacilli in the
      laryngeal sputum. All the six cases were examined by Dr. Tanaka and were found to
      have tuberculous lesions in the larynx. In the laryngeal sputum of most cases of
      laryngeal tuberculosis with symptoms, tubercle bacilli have been frequently
      demonstrated, while in some cases contaminated laryngeal sputum was obtained only
      after a long series of examinations. 5. Microscopical examination of the sputum
      plays a significant part in the diagnosis of tuberculosis.

PMID- 19868092
TI  - THE CULTIVATION OF TRICHOMONAS OF THE HUMAN MOUTH (TETRATRICHOMONAS HOMINIS).
AB  - Trichomonades from the mouth were studied by Steinberg who proposed to group them
      into three distinct types; namely, Trichomonas elongata, Trichomonas caudata, and
      Trichomonas flagellata. Doflein (3) regards them as probably identical with
      Trichomonas hominis. Opinions differ as to whether or not Trichomonas vaginalis
      Donne and Trichomonas hominis Grassi are the same species. Lynch, for instance,
      believes that they are the same species, while von Prowazek (4), Bensen (5), and
      others (6, 7) insist that they are different types. Bensen's view seems to be
      well supported by the difference alleged to be found between the mode of
      encystment in the two trichomonades, were it not for the fact that our knowledge
      about the so called cyst of trichomonades is still obscure. According to
      Alexeieff (8) many of the so called cysts were evidently blastomyces contained in
      the cell body of the trichomonas. An autogamy alleged to take place in cysts as
      described by Bohne and von Prowazek (9) has not been confirmed by Dobell (10).
      And Wenyon (11) contends that it has never been found possible to produce any
      development of these cysts outside the body on the warm stage as can be done with
      the cysts of Entamoeba coli. Therefore, it is still premature to take the process
      of encystment into consideration as far as the classification of trichomonas is
      concerned. On the other hand, Rodenwaldt (12) seems to think that there are many
      species of trichomonas in the human intestines, and Wenyon has described a new
      trichomonas from the human intestines (Macrostoma mesnili Wenyon). Further
      cultural studies in the morphology and biology of these organisms must be carried
      out in order to solve these problems. In the light of modern investigations there
      are five subgenera to be included under the genus Trichomonas Donne. They are as
      follows: (1) Protrichomonas Alexeieff, with three anterior flagella, without an
      undulating membrane. (2) Trichomastix Biitschli) with three anterior flagella and
      a trailing flagellum (Schleppgeissel) without an undulating membrane. (3)
      Trichomonas Donne, with three anterior flagella and an undulating membrane. (4)
      Macrostoma Alexeieff, Amend, Wenyon (11), with three anterior flagella and an
      undulating membrane wedged in a deep groove (peristome). (5) Tetratrichomonas
      Parisi (13), with four anterior flagella and an undulating membrane. As far as
      our culture trichomonas from the human mouth is concerned, it has been shown that
      it is not strictly a trichomonas and that it should be classed under the subgenus
      Tetratrichomonas.

PMID- 19868093
TI  - THE DRUG-FASTNESS OF SPIROCHETES TO ARSENIC, MERCURIAL, AND IODIDE COMPOUNDS IN
      VITRO.
AB  - In the foregoing experiments we attempted to determine whether or not, by
      subjecting several varieties of spirochetes to increasing doses of certain
      chemotherapeutic agents, a gradual increase of resistance to the latter could be
      shown. For this purpose, pure cultures of Treponema pallidum, Treponema
      microdentium, and Spirochoeta refringens were used against the action of
      salvarsan, neosalvarsan, bichloride of mercury, and iodine-iodide potassium
      solution in vitro. For culture media, the usual ascites-broth-tissue medium as
      well as solid ascites-agar-tissue medium was used. After permitting the
      spirochetes to grow for a fortnight in media containing certain quantities of
      each drug, transfers were made from tubes showing various degrees of growth to
      the next series of tubes containing the same drug in still higher concentrations,
      and similar transfers repeated every 2 weeks. The results of the experiments may
      be briefly summarized as follows: 1. Treponema pallidum and Treponema
      microdentium have, within 3 to 4 months, increased their tolerance to salvarsan
      and neosalvarsan to five and one-half times their original mark. With Spirochata
      refringens the increase was about three times. 2. Against the action of
      bichloride of mercury, the amount of increased tolerance of Treponema pallidum
      was about 35 to 70 times the original, while that of Treponema microdentium was
      about 10 times as much and was reached within 10 weeks. Spirochata refringens
      resisted 30 times the original dose. 3. There was an unmistakable increase of
      resistance of these spirochetes to the action of the iodine-iodide solution
      (Lugol's solution) when they were grown for several generations in fluid media
      containing the iodine solution, but the rate of increase between the initial and
      the acquired tolerance was slight. In general, the addition of Lugol"s solution
      to fluid media has a weak inhibitory influence upon the growth of the
      spirochetes, requiring for the total suppression of growth a quantity of over 0.7
      cc. to 5 cc. of the culture media. The tolerance reached was for about three
      times that amount. 4. A similar tolerance phenomenon has not been established
      when employing a solid instead of a fluid medium containing the drugs. No
      explanation is offered except a suggestion that the drugs held in the agar do not
      enter into combination with certain tissue constituents of the medium as they are
      able to do with tissue elements in fluid media. This may be a factor necessary
      for inducing drug tolerance in these organisms in vitro. 5. The increased drug
      fastness in vitro has a limit beyond which no further advance can be made. This
      limit varies with different species of spirochetes. 6. The acquired drug-fastness
      in vitro gradually disappears when the spirochetes are cultivated again in the
      drug-free media for several generations.

PMID- 19868094
TI  - THE RESISTANCE OF SPIROCHETES TO THE ACTION OF HEXAMETHYLENETETRAMINE DERIVATIVES
      AND MERCURIAL AND ARSENIC COMPOUNDS.
AB  - The majority of the 76 new compounds possessed spirocheticidal powers ranging
      between 1: 1,000 (30) to 1:2,500 (14), while only 2 attained the power of
      1:5,000, 1 of 1: 25,000, and 2 of 1: 50,000. On the other hand, 8 killed the
      spirochetes in a dilution of 1: 750, 10 in 1:500, 7 in 1:250. 1 in 1: 100, and 1
      in 1:50. It may be mentioned that the 2 (M1, M4) of 1:50,000 and 1 (M7) of
      1:25,000 belong to the mercury compounds, and that mercuric chloride kills the
      organisms in a dilution of 1: 100,000 under the same experimental conditions. It
      is also interesting to compare some of the more common chemicals and therapeutic
      reagents. Phenol is spirocheticidal in a dilution of 1: 2,500, lysol in 1: 5,000,
      formalin in 1: 750, salvarsan in 1: 7,500, and neosalvarsan in 1: 2,500. Thus, of
      the new compounds there are at least 14 which have the same spirocheticidal power
      in vitro as has neosalvarsan. It is of interest to note that nine compounds
      possessing the 1:1,000 spirocheticidal power showed only one-tenth of the
      antiseptic action when tested upon Bacillus dysenteriae and Streptococcus, while
      some showed an even greater difference in this respect. Nos. 16, 21, 29, 218, and
      244 were effective in a dilution of 1:2,500 for spirochetes and in a 1:100 or
      lower dilution for the bacteria just referred to. Preparations 46 and 84 appear
      to exert about the same effect both on the spirochetes and the bacteria, neither
      being very strong. Atoxyl killed the spirochetes in a 1:50 dilution. One of the
      most striking results was obtained with various hemolytic substances. Neufeld and
      von Prowazek found that spirochetes, unlike bacteria in general, are highly
      susceptible to the lytic action of sodium taurocholate and saponin, and they
      considered that this phenomenon was of differential diagnostic value in
      determining plant and animal organisms. Their observations were confirmed by
      Gonder, who found, however, that spirochetes, especially treponemata, offer a
      great deal of resistance at the beginning, but finally undergo lysis, with their
      cell bodies swollen up or macerated. In the present experiment we have found that
      these substances not only bring about cytolysis of the spirochetes in higher
      concentrations, but also kill them without causing a gross destruction of the
      cells in very high dilutions; thus, sodium cholate in 1: 5,000, sodium
      glycocholate and taurocholate in 1: 2,500 each, saponin in 1:7,500. Sodium
      oleate, one of the most powerful hemolytic agents killed the spirochetes in 1:
      7,000, and cobra lecithide and native cobra venom in a dilution of 1:1,000 each.
      Neither sodium nor potassium iodide displayed any marked spirocheticidal property
      (1: 10 only), while iodine in the form of Lugol's solution was able to kill them
      at 1:75.

PMID- 19868095
TI  - THE INFLUENCE OF CARBOHYDRATES ON THE CULTIVATION OF SPIROCHETES.
AB  - Various carbohydrates have been added to the fluid cultures of different strains
      of spirochetes in order to determine the behavior of the latter toward the
      carbohydrates. In the present experiment, amygdalin, arabinose, beerwort,
      dextrin, galactose, glycogen, glucose, inulin, lactose, levulose, maltose,
      mannite, raffinose, saccharose, and starch were tested with seven strains of
      Treponema pallidum and one strain each of Treponema calligyrum, Treponema
      microdentium, Treponema mucosum, and Spirochata refringens. The results may be
      summarized as follows: 1. In the media containing glycogen and glucose, Treponema
      microdentium did not grow as vigorously as in other sugar media, and an earlier
      degeneration set in. One strain of the pallidum and the calligyrum and mucosum
      showed a poor growth in the glycogen medium. Similarly, there was little growth
      in the second transfer of these spirochetes in the glucose medium. The growth of
      the spirochetes in the media containing carbohydrates other than those Just
      mentioned was generally good, and no difference could be distinguished between
      these and the control cultures without any carbohydrate. The only phenomenon
      which might be interpreted as indicating a favorable influence of these media
      upon growth was the abundant growth of the mucosum, which showed uniform length,
      regular curves, and active motility somewhat better than in the sugar-free
      medium. 2. The height of acidity was found in the cultures containing glycogen
      and glucose in the microdentium, amounting to 0.1 N 4.8 cc. for 10 cc. of the
      fluid culture. In the other sugar media the acidity varied between 0.1 N 2 cc.
      and 0.1 N 3.2 cc. for the same amount. In the control cultures, the acidity
      fluctuated from 0.1 N 0.8 cc. to 0.1 N 2 cc. There was no visible alteration in
      the appearance of the media after the spirochetes had grown for 3 or 4 weeks. In
      the case of Treponema microdenlium, a slight opalescence developed in the
      glycogen and glucose media after several weeks' standing, but there was no
      precipitation or coagulation of the proteins of the culture media. 3. There was
      no unusual morphological change in the spirochetes grown in the media containing
      any of the carbohydrates employed. The only phenomena which should be mentioned
      are (a) the frequent presence of the terminal appendages (or projections) in the
      refringens, and in most of the pallidum strains, and (b) the appearance of
      minute, retractile spherical bodies along the side of the spirochetes in the
      microdenlium cultivated in the glucose or glycogen media. Judging from the
      earlier degeneration of the species in the above mentioned media, these peculiar
      bodies may be interpreted as indicating a phase of plasmoptysis associated with
      the unfavorable surroundings prior to degeneration. Experimental evidence was not
      found for considering these spherules as a resistant or spore form of the
      spirochete.

PMID- 19868096
TI  - THE ABSORPTION OF FAT IN PARTIALLY, AND IN COMPLETELY DEPANCREATIZED DOGS.
AB  - It was found that dogs with a subcutaneous transplant secreting and discharging
      pancreatic juice externally absorbed no more fat than dogs in which the
      pancreatic remnant was undergoing rapid atrophy and sclerosis. Hence, the
      condition of the pancreatic tissue remaining in the body does not influence the
      amount of fat absorbed by the intestine. The absorption of fat by the intestinal
      mucous membrane is always markedly disturbed when the pancreatic secretion is
      excluded from the intestine. After the complete removal of all pancreatic tissue
      from an animal, the absorption of considerable amounts of fat can still take
      place.

PMID- 19868097
TI  - SOME FIELD EXPERIMENTS BEARING ON THE TRANSMISSION OF BLACKHEAD IN TURKEYS.
AB  - It seems, therefore, pending further field tests on a larger territory, that the
      following facts are fairly well established by the above experiments. 1. Healthy
      turkeys may be raised in an incubator from eggs of infected birds. In the above
      experiments all remained well to August 14, the end of the hen exposure test,
      when they were 12 weeks and 4 days old. The first death occurred 2 weeks after
      the beginning of exposure to actual disease, when they were more than 14 weeks
      old. 2. Hens from a blackhead farm and from a farm free from turkeys did not
      convey the disease to the incubator turkeys on uninfected land. 3. The infection
      is either not transmitted at all or only under exceptional conditions by turkeys
      in the early acute stage. It is probably carried and shed by those birds which
      have successfully passed through an attack. Any definite statement concerning the
      mode of transmission of the infection cannot be made. The vehicle is unknown. The
      nature of the disease makes it probable, however, that it is introduced with the
      food, that it lodges first in one or both ceca, and that fecal matter is the
      vehicle. During the entire season, portions of the small intestines of all the
      turkeys that died or were killed were sectioned and examined both with reference
      to the possible presence of coccidia and of any preliminary stage of Amoeba
      meleagridis. Sections were studied from the upper (duodenum), middle, and lower
      portions. A few coccidia cysts were found in two turkeys and are referred to more
      in detail elsewhere. In a third turkey an intracellular parasite was seen which
      is very minute and which differs from those usually met with in birds. It is
      tentatively placed with the coccidia. It was not seen in any other case although
      searched for to obtain more material for study. It may be that we have an
      aberrant parasite to deal with which comes from the insects eaten and obtains
      lodgment in rare cases only. The existence of any earlier stages of the blackhead
      parasites in the small intestine whence they move down into the ceca is
      contradicted by the focal lesions found in the ceca and by the fact that in many
      cases only one cecum is attacked and this only in a single, restricted area. If
      the parasites multiply higher up we should expect both ceca to become infected.
      There is some evidence pointing to a greater resistance of older birds than is
      usually presented by young turkeys. Thus, the total mortality (including those
      chloroformed while sick) following exposure on the infected farms and to the
      yearling turkey-hens was nine out of nineteen exposed, or a trifle less than 50
      per cent. This figure is usually exceeded among those exposed immediately after
      hatching. The surviving turkeys are still well at the present time (January
      1917). The other kind of evidence is derived from the histological examination of
      the lesions in the liver and ceca. In these organs the process was rather early
      associated with extensive infiltration of roundish cells, while the tendency to
      necrosis was relatively slight. The lesions of the walls of the ceca were
      characterized by a marked thickening of the wall with little or no necrosis and
      exudation of fibrin. In repeating tests of this kind it will be well for the
      experimenter to bear in mind that they are no longer laboratory experiments but
      conform to natural occurrences. The infection is not isolated in pure culture but
      is associated in the body of the carrier with unknown factors, both normal and
      pathological. The virus, if such it may be called, may be mixed with different
      injurious agents in different localities. It may be favored by various protozoan
      or higher parasites accidentally present, and by digestive disturbances due to
      improper feeding. To utilize animals infected in the natural way as a source of
      virus, is to put the experiments into nature's hands as far as possible without
      losing control of the main conditions. Such experiments cannot, therefore, be
      completely reproduced at will as is possible in the laboratory with pure
      cultures, and the results may vary from place to place. They are practical rather
      than scientific tests in the sense that the practical test may involve unknown
      factors largely eliminated in the scientific or laboratory test.

PMID- 19868098
TI  - A NOTE ON COCCIDIA IN SPARROWS AND THEIR ASSUMED RELATION TO BLACKHEAD IN
      TURKEYS.
AB  - Of 54 sparrows examined in or near Princeton, coccidia were found in 43, or 80
      per cent. Most of the negative cases were encountered in November and December.
      In the summer and fall practically all were infected. These figures agree closely
      with Hadley's, who found 79 per cent infected from May to December. Cultures of
      feces on agar showed that, at least in this locality, the infecting species
      belongs to the genus Isospora or Diflospora and not to Eirneria. In a recent
      paper by Hadley, which came into our hands after the manuscript had gone to
      press, the author now refers blackhead to invasions of Trichomonas. It is not
      possible to consider here the evidence on which this conclusion is based.

PMID- 19868099
TI  - INTESTINAL OBSTRUCTION : AN EXPERIMENTAL STUDY OF THE INTOXICATION IN CLOSED
      INTESTINAL LOOPS.
AB  - 1. Closed intestinal loops in which bacteria are first removed are compatible
      with life. 2. Closed intestinal loops in which bacteria are present but in which
      tissue necrosis is prevented, are compatible with life. 3. Closed aseptic
      intestinal loops in which the blood supply is completely occluded are compatible
      with life. 4. The normal secretions and bacterial products of the duodenum and
      jejunum are not sufficiently toxic to produce any symptoms when allowed to drain
      into the abdominal cavity. 5. Our results do not support the theory of Draper of
      a normal toxic secretion of the duodenal mucosa, neutralized by the jejunal
      mucosa, or the perverted secretion theory of Whipple. 6. Bacterial activity plus
      necrotic tissue, or the absorption of toxic products resulting from the action of
      putrefactive bacteria on necrotic tissue is the important factor in the rapid
      death in simple closed intestinal loops.

PMID- 19868100
TI  - THE INFLUENCE OF CERTAIN ORGANIC SUBSTANCES ON THE GROWTH OF THE TUBERCLE
      BACILLUS.
AB  - The power of a large number of aniline dyes to restrain the growth of Bacillus
      tuberculosis and Bacillus typhosus has been determined. Many substances have been
      found with especial restraining power for the tubercle bacillus under the
      conditions of the test. This capacity to restrain growth in the case of the
      tubercle bacillus apparently bears no simple relation to true disinfectant
      action. Opinion as to whether the active substances exert a truly specific
      activity against the tubercle bacillus or whether the activity is determined by
      the peculiar conditions imposed by the growth of this bacterium as a surface
      membrane are left for future consideration.

PMID- 19868101
TI  - PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : I. THE METABOLISM OF FASTING
      DOGS FOLLOWING PROTEOSE INJECTIONS.
AB  - Proteose injections in dogs cause vomiting, diarrhea, temperature reactions, low
      blood pressure, prostration, and, after large doses, an excess of antithrombin
      with incoagulable blood. A single proteose injection, for example one-half a
      lethal dose, causes abrupt clinical reactions in a normal dog with apparent
      complete recovery within 24 to 48 hours. The nitrogen elimination curve in a
      fasting dog under such conditions shows a great rise in total urinary nitrogen.
      The apex of the curve usually falls during the second 24 hour period following
      the injection. This rise may be over 100 per cent increase above the mean base
      line nitrogen level. It does not fall promptly to normal but declines slowly in 3
      to 5 days or more toward the original base-line (Text-fig. 1). This speaks for a
      definite cell injury with destruction of considerable protein substance due to a
      single proteose injection. The disturbance of cell equilibrium is not rapidly or
      promptly restored to normal. A dog which has received previous proteose
      injections is partially immune or tolerant to subsequent injections of proteose.
      These dogs, as a rule, show less intense clinical reactions and less rise in the
      curve of nitrogen elimination following a unit dose of standard proteose as
      compared with normal or non-immune controls. The proteose used in these
      experiments was prepared as described from material obtained in cases of
      intestinal obstruction or of closed intestinal loops. These experiments explain
      the sharp rise in blood non-protein nitrogen which follows within a few hours the
      injection of a toxic proteose. They also point to the correct explanation of the
      high non-protein nitrogen of the blood found in intestinal obstruction or with
      closed intestinal loops.

PMID- 19868103
TI  - THE EFFECT OF COLD UPON MALARIA PARASITES IN THE MOSQUITO HOST.
AB  - The experiments reported here have shown that the parasite of tertian malaria in
      the mosquito host is able to survive exposure to a temperature of 30 degrees F.
      for a period of 2 days, 31 degrees F. for 4 days, and a mean temperature of 46
      degrees F. for 17 days. In a smaller series of tests the sporonts of the estivo
      autumnal parasite have shown a resistance to temperatures as low as 35 degrees F.
      for 24 hours.

PMID- 19868102
TI  - PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : II. THE METABOLISM OF DOGS
      WITH DUODENAL OBSTRUCTION AND ISOLATED LOOPS OF INTESTINE.
AB  - Dogs with isolated loops of small intestine show many evidences of intoxication.
      A study of the total nitrogen elimination shows a great rise above the normal
      base-line minimum of the fasting period (Table II). This means that the
      intoxication is associated with a great destruction of body protein, and explains
      the high non-protein nitrogen of the blood which was observed and reported
      previously (2). Injection of a proteose obtained from a closed intestinal loop
      will cause a similar rise in the nitrogen elimination curve. This furnishes more
      evidence that the intoxication observed in association with a closed intestinal
      loop is in reality a proteose intoxication. Dogs injected with sublethal doses of
      proteose will show a definite tolerance to subsequent injection, and will show
      much less acute intoxication after the isolation of a closed intestinal loop
      (Table 1). These immune or tolerant dogs show a much less pronounced rise in the
      nitrogen elimination curve during proteose intoxication of any type. This
      indicates that the tolerance or immunity to proteose gives more protection for
      the body proteins against the injury which these toxic proteoses inflict upon the
      body cells. Complete duodenal obstruction combined with a gastrojejunostomy gives
      a chronic type of intestinal obstruction associated with little vomiting, which
      is peculiarly suited to metabolism study (Table IV). Such duodenal obstructions
      show a definite and sustained rise in the curve of nitrogen elimination above the
      normal base-line level. These dogs, too, are tolerant to injections of standard
      toxic proteoses. Control ether anesthesia experiments show little if any rise in
      the curve of nitrogen elimination (Table VI). Control laparotomy experiments show
      a definite rise in the curve of nitrogen elimination, but a rise which is small
      compared with the rise noted in the intoxication of duodenal obstruction or of
      isolated intestinal loops. It is probable that the tissue injury and
      disintegration associated with the wound reaction are responsible for the general
      reaction. We may assume that protein split products from the wound area are
      absorbed and are responsible for the general reaction observed. We propose to
      assume that the intoxications here studied are associated with a definite
      proteose intoxication, which is capable of initiating and continuing a profound
      injury of tissue protein. One index of this protein injury is the great and
      sustained rise in the curve of total nitrogen elimination.

PMID- 19868104
TI  - THE PASSAGE OF NEUTRALIZING SUBSTANCES FROM THE BLOOD INTO THE CEREBROSPINAL
      FLUID IN POLIOMYELITIS.
AB  - The cerebrospinal fluid taken very early and quite late in the course of acute
      poliomyelitis exhibits no neutralizing action on filtered poliomyelitic virus.
      The blood serum on the 6th day of the disease already contains the neutralizing
      principles. The injection of sterile horse serum into the cerebrospinal meninges
      in monkeys increases their permeability, so that they permit the immunity
      neutralizing principles passively injected into the blood to pass into the
      cerebrospinal fluid. The passage in passively immunized monkeys takes place
      during a relatively brief space of time and apparently only while the
      inflammatory reaction produced by the horse serum is at its height. It is
      established for monkeys and rendered probable for man that the intraspinal
      injection of immune serum in poliomyelitis is curative. In monkeys normal serum
      exerts no such action, and at present nothing can be stated definitely regarding
      the therapeutic effect of normal serum in man except that probably any benefits
      which may arise from its employment would be attributable not to the action of
      the serum as such, but to the escape of circulating immunity principles in the
      blood made possible by the aseptic inflammation set up by it in the meninges. As
      the immunity principles appear in the blood only after several days, and the
      reported favorable effects of the immune serum treatment relate to the first days
      of illness, the employment of normal serum is thus not indicated, while that of
      an immune serum is.

PMID- 19868105
TI  - NEUTRALIZATION OF THE VIRUS OF POLIOMYELITIS BY NASAL WASHINGS.
AB  - 1. The results of 56 experiments have shown that washings of the nasal and
      pharyngeal mucosas possess definite power to inactivate or neutralize the active
      virus of poliomyelitis. 2. This power is not absolutely fixed, but is subject to
      fluctuation in a given person. Apparently inflammatory conditions of the upper
      air passages tend to remove or diminish the power of neutralization. But
      irregularities have been noted, even in the absence of these conditions. 3. Too
      few tests have been made thus far to ascertain whether adults and children differ
      with respect to the existence of this neutralizing property in the nasal
      secretions. While the inactivating property was absent from the secretions of one
      child during the first days of poliomyelitis, it was present in another to whom
      immune serum was administered, and in still another on the 15th day of illness
      when convalescence was established. 4. The neutralizing substance is water
      soluble and appears not to be inorganic; it appears to be more or less
      thermolabile, and its action does not depend upon the presence of mucin as such.
      5. It is suggested that the production of healthy carriers through contamination
      with the virus of poliomyelitis may be determined by the presence or absence of
      this inactivating or neutralizing property in the secretions. Whether this effect
      operates to prevent actual invasion of the virus and production of infection can
      only be conjected. Probably accessory and not the essential element on which
      defense against infection rests. It is more probable that other factors exist
      which help to determine the issue of the delicate adjustment between
      contamination and infection.

PMID- 19868106
TI  - THE RELATION OF THE MENINGES AND CHOROID PLEXUS TO POLIOMYELITIC INFECTION.
AB  - Among the mechanisms which defend the body from infection with the virus of
      poliomyelitis is the meningeal-choroid plexus complex, which normally is capable
      of excluding the circulating virus from the central nervous organs. The complex
      plays a part also in preventing infection from virus present upon the nasal
      mucosa. Aseptic fluids which irritate, inflame, or even slightly alter the
      integrity of the meninges and choroid plexus diminish or remove their protective
      function. Normal monkey or horse serum, isotonic salt solution, and Ringer's and
      Locke's solutions, when injected into the meninges, promote infection with the
      virus of poliomyelitis introduced into the blood, the nose, or the subcutaneous
      tissues. Simple lumbar puncture and the withdrawal and return of the
      cerebrospinal fluid in normal monkeys, hemorrhage having been absolutely avoided,
      do not promote infection with virus injected into the blood; while the
      replacement of the cerebrospinal fluid of one monkey with that of another does in
      some instances lead to infection. Simple lumbar puncture attended with even very
      slight hemorrhage opens the way for the passage of the virus from the blood into
      the central nervous tissues, and thus promotes infection. Hence, changes in the
      structure or function of the meningealchoroid plexus complex, too slight to be
      detected by chemical and cellular changes in the cerebrospinal fluid or by
      morphological alterations, suffice to diminish in an essential manner its
      protective powers. Of all the irritant fluids tested, immune serum alone injected
      into the meninges is not succeeded by infection from the virus introduced into
      the blood. The protective property of the immune serum is capable of overcoming
      the promoting action of normal monkey and horse serum and the other irritants
      mentioned. The importance first of the meningeal-choroid plexus complex in
      preventing infection with the virus of poliomyelitis, and next of immune serum in
      offsetting the disadvantages and dangers arising from defects in the mechanism is
      apparent, as is the bearing of the experiments reported on the serum therapy of
      epidemic poliomyelitis.

PMID- 19868107
TI  - SURVIVAL OF THE POLIOMYELITIC VIRUS FOR SIX YEARS IN GLYCEROL.
AB  - The virus of poliomyelitis contained within the spinal cord and medulla of human
      beings and monkeys withstands glycerolation for many years. The specimens tested
      had been kept for 4 and 6 years respectively in 50 per cent glycerol at
      refrigerator temperature. The symptoms and lesions caused by this virus are
      identical with those produced by that contained in the more recently collected
      spinal cord and medulla. The specimens had lost a part of their activity under
      the conditions described, necessitating larger and repeated doses to induce
      infection. Whether this difference is due merely to quantitative reduction in
      number of viable microorganisms or to qualitative alterations under the influence
      of the mildly antiseptic glycerol has not been determined. An ineffective
      inoculation of tissues containing the virus does not increase resistance, but
      rather diminishes it, so that a subsequent injection, inadequate in itself, may
      cause experimental poliomyelitis. This power of survival under adverse conditions
      may not be without significance in respect to the recrudescence of poliomyelitis
      in a given locality and after a lapse of years. Hitherto this phenomenon has been
      accounted for by assuming a fresh importation of a virus of pronounced pathogenic
      power. It is possible that the explanation in some instances resides in the
      renewed activity of specimens of the virus surviving from a previous epidemic,
      while in other instances a fresh introduction actually takes place from a remote
      focus of infection. The infectious nervous tissues employed in these experiments
      did not yield in culture streptococci or other ordinary bacteria.

PMID- 19868108
TI  - THE CULTIVATION AND IMMUNOLOGICAL REACTIONS OF THE GLOBOID BODIES IN
      POLIOMYELITIS.
AB  - Two additional cultures of globoid bodies, obtained from the nervous tissues of
      monkeys in which experimental poliomyelitis was produced, and identical with the
      original cultures described by Flexner and Noguchi, are reported in this paper.
      The highly parasitic cultures, like Treponema pallidum, are refractory to
      artificial cultivation. After long cultivation outside the body, the globoid
      bodies acquire saprophytic properties and then grow more readily and in a
      considerable variety of media, provided, however, that they carry a certain
      quantity of protein matter not denatured. The rabbit responds slightly with the
      production of antibodies to the injection of cultures of the globoid bodies. The
      monkey responds only occasionally under the same conditions and apparently only
      when the cultures are injected into the central nervous system. This response is
      small and at most leads to slight reactions of agglutination and complement
      deviation with the cultures. The serum obtained from monkeys recovered from
      experimental poliomyelitis shows even less agglutination and no complement
      deviation. The maximal agglutinative and morphological changes produced in the
      globoid bodies cultivated in immune monkey serum are obtained in the first
      generation; after several subcultures in the immune serum, the reversion to
      normal takes place in one generation in a non-immune medium. The serum of human
      beings in the acute or early subacute stages of poliomyelitis gives no complement
      deviation with the antigen derived from the globoid bodies. The cultivation of
      the saprophytized globoid bodies through several generations in immune monkey or
      human serum did not confer upon them pathogenic properties for monkeys. The serum
      of human beings and monkeys which have survived attacks of poliomyelitis does not
      fix complement in the presence of antigens prepared from organs of the monkey
      succumbing to the experimental disease. The globoid bodies and Treponema pallidum
      present many analogies in cultural, immunological, and pathogenic properties.

PMID- 19868109
TI  - THE PATHOLOGIC EFFECTS OF STREPTOCOCCI FROM CASES OF POLIOMYELITIS AND OTHER
      SOURCES.
AB  - Streptococci cultivated from the tonsils of thirty-two cases of poliomyelitis
      were used to inoculate various laboratory animals. In no case was a condition
      induced resembling poliomyelitis clinically or pathologically in guinea pigs,
      dogs, cats, rabbits, or monkeys. On the other hand, a considerable percentage of
      the rabbits and a smaller percentage of some of the other animals developed
      lesions due to streptococci. These lesions consisted of meningitis, meningo
      encephalitis, abscess of the brain, arthritis, tenosynovitis, myositis, abscess
      of the kidney, endocarditis, pericarditis, and neuritis. No distinction in the
      character or frequency of the lesions could be determined between the
      streptococci derived from poliomyelitic patients and from other sources.
      Streptococci isolated from the poliomyelitic brain and spinal cord of monkeys
      which succumbed to inoculation with the filtered virus failed to induce in
      monkeys any paralysis or the characteristic histological changes of
      poliomyelitis. These streptococci are regarded as secondary bacterial invaders of
      the nervous organs. Monkeys which have recovered from infection with streptococci
      derived from cases of poliomyelitis are not protected from infection with the
      filtered virus, and their blood does not neutralize the filtered virus in vitro.
      We have failed to detect any etiologic or pathologic relationship between
      streptococci and epidemic poliomyelitis in man or true experimental poliomyelitis
      in the monkey.

PMID- 19868110
TI  - A REPORT ON THE SERUM TREATMENT OF TWENTY-SIX CASES OF EPIDEMIC POLIOMYELITIS.
AB  - 1. Serum taken from recently recovered cases of poliomyelitis may be employed in
      its treatment and probably yields the best results. 2. When sterile for ordinary
      bacteria, free of corpuscles and hemoglobin, and when injected by the gravity
      method, observing well known rules of caution, it may be employed without danger.
      3. The serum should be injected both intraspinally and intravenously, the latter
      either directly or by way of the subcutaneous tissues. 4. The earlier in the
      course of the disease the serum is employed in suitable doses, the more promise
      there is of benefit. 5. The action of the serum appears to be more precise and
      definite in arresting paralysis than in rapidly bringing about its retrogression.
      6. The decision to employ the serum should rest upon a clinical examination
      supported by the results of the microscopic and chemical study of the
      cerebrospinal fluid. 7. The question of multiple and repeated injections of the
      serum has not yet been worked out. In the cases here reported and especially in
      the group in which no paralysis existed at the time of the first injection, the
      pathologic process either did not progress at all, or where there was extension,
      as in Cases 14 and 15, the upper segment of the spinal cord became rapidly
      involved, and was followed by respiratory paralysis and death. Probably in cases
      in which some degree of muscular weakness develops soon after the injection of
      serum, reinjection 12 to 24 hours later may be advantageous. The temperature
      curve may serve to indicate the time for reinjection. 8. The favorable results
      thus far achieved in human beings by means of the immune serum support and extend
      those obtained experimentally in monkeys and indicate, as was foreseen, that the
      milder or less fatal form of poliomyelitis appearing in man is even more amenable
      to the serum treatment than is the highly fatal disease produced by inoculation
      in monkeys.

PMID- 19868111
TI  - EXPERIMENTS ON THE ROLE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL
      TUBERCULOSIS IN MICE : II. EFFECT OF CANCER IMMUNITY ON RESISTANCE TO
      TUBERCULOSIS.
AB  - Mice so x-rayed as greatly to reduce the lymphoid tissue are rendered highly
      susceptible to tuberculous infection. On the other hand) when a marked
      lymphocytosis is induced by first immunizing mice against, and then inoculating
      them with cancer, the resistance to tuberculous infection is greatly enhanced.
      This heightened resistance may be set aside and even changed to a state of
      increased susceptibility to the infection by again depleting the lymphocytes by
      means of the x-ray.

PMID- 19868112
TI  - THE TRANSPLANTATION OF SPLENIC TISSUE INTO THE SUBCUTANEOUS FASCIA OF THE ABDOMEN
      IN RABBITS.
AB  - We have not found in the literature a report of an instance of permanent homoio
      or autotransplantation of the spleen, or of the probably closely related spleno
      and hemolymph glands. Spleen autotransplants with considerable difficulty as
      compared with thyroid, parathyroid, ovary, or adrenal cortex. This may be due to
      its complex anatomical structure. An instance of a permanent autotransplant has
      been observed. None of our attempts to homoiotransplant it were successful beyond
      the usual taking and persistence for 2 or 3 weeks, common to all homoiografts.
      The successful permanent subcutaneous autotransplantation had all the
      morphological characteristics of a fully differentiated and functionally active
      spleen. This method of transplantation would seem to offer a means of learning
      more of the normal development, regeneration, and function of this complex
      tissue.

PMID- 19868113
TI  - A NOTE ON THE PRODUCTION OF ANTIPNEUMOCOCCUS SERA.
AB  - Horses immunized to Type I pneumococci developed serum, 0.1 cc. of which
      protected against 0.5 cc. of a virulent culture, 0.000001 cc. of which killed
      mice in less than 40 hours. Protective tests of serum from horses immunized to
      Type II organisms varied, 0.1 cc. protecting, however, in certain instances
      against 0.1 and 0.01 cc. of virulent homologous culture. Types I and II sera
      obtained in our experiments with culture sediment and whole culture did not vary
      markedly for a given type and corresponded closely in their protective titer with
      samples of sera received from The Rockefeller Institute Hospital. It is therefore
      evident that the following minimum standard of 0.1 cc. of serum to protect mice
      against at least 0.2 cc. of virulent cultures can and should be maintained when
      serum is to be used for the treatment of cases. By further study and comparison
      of these different methods of immunization it is hoped that sera of greater
      potency may be produced, but as yet this has only been accomplished in
      exceptional instances. A horse immunized with Type III (Pneumococcus mucosus)
      developed serum having a slight degree of protection for mice against the
      corresponding organisms. This serum was sufficiently potent, however, to cause
      prompt and complete agglutination when combined with fresh untreated homologous
      organisms, thus avoiding the preliminary treatment to remove the capsule which
      has previously been held necessary. As a diagnostic aid in the differentiation of
      pneumococcus strains, the serum has proved of distinct value.

PMID- 19868114
TI  - EXPERIMENTAL STUDIES UPON LYMPHOCYTES : I. THE REACTIONS OF LYMPHOCYTES UNDER
      VARIOUS EXPERIMENTAL CONDITIONS.
AB  - A simple method is presented by which, with the diffusion of trypan blue into the
      nucleus as a criterion of cell injury, it is possible to study quantitatively the
      effect of various agencies upon the small thymus cells and upon the tissue
      lymphocytes. Preliminary studies with this method have led us to the following
      conclusions, which, however, unless otherwise stated, may be taken as applying
      only to the lymphocytes of the rat thymus. 1. The small thymus cells, when
      suspended in balanced phosphate solutions, show no distinct reaction to
      variations in hydrogen ion concentrations ranging between P(h) 7.0 and P(H) 7.8.
      Beyond P(H) 7.0 there is a sudden increase in the permeability of the cells to
      the dye; plasmolysis of the cells occurs when the alkalinity exceeds P(H) 8.0. 2.
      Heating to 49 degrees or 50 degrees C. is accompanied by a critical increase in
      the permeability of the cells to the dye. 3. The injury caused by lack of oxygen
      can be demonstrated by the increase in the number of stained cells. 4. The
      addition of serum to suspensions of thymus cells or tonsil lymphocytes greatly
      inhibits the diffusion of the trypan into the cells. The protection afforded is
      roughly proportionate to the amount of serum added. Gelatin also exerts a marked
      protective influence; egg albumin affords a partial protection; starch and gum
      arabic are inert. Hemoglobin and cholesterol do not modify the stainability of
      the cells. Arsenious sulfide in weak concentrations partially inhibits the
      diffusion of the dye. Colloidal iron is without effect, and is precipitated about
      the cells. 5. The toxicity of the photodynamic substance, hematoporphyrin, and of
      an impure chlorophyll solution in the presence of sunlight could be strikingly
      demonstrated by the greatly increased permeability of the cells to the stain. 6.
      Acute and chronic inanition produces an increased fragility of the cells. The
      protective power of the serum in acute starvation appears to be increased. 7. The
      small thymus cells of old animals are more readily injured than are those of
      young ones, as indicated by the increased proportion of stained cells. 8. The
      method has been applied to the demonstration of the action of cytotoxic immune
      sera for rat thymus cells and for human tonsil lymphocytes in vitro. Further
      experiments dealing with the question of specificity are in progress. The
      cytotoxins are inactivated by the addition of complement. Thermostabile
      cytagglutinins have also been produced.

PMID- 19868115
TI  - THE NORMAL FATE OF ERYTHROCYTES : I. THE FINDINGS IN HEALTHY ANIMALS.
AB  - The phagocytosis of red corpuscles, while frequent in the normal dog, rat, and
      guinea pig, is slight in man, the rhesus monkey, and many rabbits. In cats it is
      always negligible in amount and frequently absent. Phagocytosis will not suffice
      as a general explanation of normal blood destruction. When the liver, spleen, and
      bone marrow of the cat, dog, rabbit, or monkey are slowly perfused with
      defibrinated blood or Locke"s solution, bodies are given off into the fluid which
      have the appearance of red corpuscles that have lost their hemoglobin but
      retained the rest of their cell substance. These bodies possess many of the
      properties supposedly distinctive of red corpuscles. They are the product of
      disordered parenchymal cells. By a special method, it has proved possible to
      search the body, organ by organ, and the circulating blood also, for
      disintegrating red corpuscles. Shadows of red cells are not present anywhere, nor
      are hemolyzing red cells found. A hemolytic process, in the ordinary sense of the
      term, can scarcely play an. important part in normal blood destruction. Instead,
      it is certain that some red corpuscles, at least, are destroyed in another way;
      namely, by fragmentation. Normal blood regularly contains small numbers of
      fragmentation forms-microcytes and poikilocytes-and accumulations of them are
      regularly present in the spleen, but are found only inconstantly in the other
      organs. The fragments are in evident process of further subdivision. They occur
      not only in species in which phagocytosis as a means of cell destruction is
      negligible (cats), but also in animals in which it is an important process (dogs,
      some rabbits). The method of study that we have employed is well suited to
      disclose how the blood is destroyed. The importance of cell fragmentation in this
      connection is indicated by our failure to find any other means of destruction,
      save only the phagocytosis already known. Further facts indicating the importance
      of fragmentation are presented in our second paper, where a general discussion
      will also be found.

PMID- 19868116
TI  - THE NORMAL FATE OF ERYTHROCYTES : II. BLOOD DESTRUCTION IN PLETHORIC ANIMALS AND
      IN ANIMALS WITH A SIMPLE ANEMIA.
AB  - 1. The increased destruction of red cells in animals rendered plethoric by
      transfusion takes place predominantly by a fragmentation of the corpuscles
      without loss of hemoglobin. 2. The microcytes and poikilocytes observed in
      animals with a severe anemia due to hemorrhage are not put forth as such by the
      bone marrow, but are portions of cells fragmented while circulating. 3. The cells
      thus fragmented are for the most part those newformed to meet the exigencies of
      the situation. Such cells are in large part unable to withstand the wear and tear
      of function. There results a vicious circle. The anemia renders the bone marrow
      unable to put forth proper cells, and those it does produce are soon destroyed,
      thus prolonging the condition. A similar state of affairs probably exists in many
      human anemias. 4. The occurrence of large accumulations of microcytes and
      poikilocytes in the spleen of anemic and plethoric animals indicates that the
      organ exercises some important function in connection with these forms. The same
      is true of normal animals, for the findings in them are similar, though less
      striking. 5. The normal fate of the red corpuscles, in those species in which
      phagocytosis is negligible, is to be fragmented one by one, while still
      circulating, to a fine, hemoglobin-containing dust. The cell fragments are
      rapidly removed from the blood, but their ultimate fate remains to be determined.
      The facts indicate that they are removed from the blood by the spleen, and under
      exceptional conditions, by the bone marrow.

PMID- 19868117
TI  - THE ELIMINATION OF IRON AND ITS DISTRIBUTION IN THE LIVER AND SPLEEN IN
      EXPERIMENTAL ANEMIA.
AB  - Blood destruction due to a single injury, as by sodium oleate, or acting through
      a short period of time, as by toluylenediamine or hemolytic immune serum, is not
      characterized, in the absence of hemoglobinuria, by an increased elimination of
      iron in the urine. This holds, not only for the evanescent injury caused by
      sodium oleate, but also for the severe type caused by hemolytic immune serum, in
      which a progressive destruction of the blood may persist for 2 weeks or more with
      constant evidence of the disintegration of erythrocytes as shown by bile pigment
      in the urine. This finding is in accord with previous investigations of anemia in
      both man and animals. Likewise, no striking increase is evident, under such
      circumstances, in the percentage of iron excreted in the feces. The total amount
      of iron in the feces has been notably increased in two experiments with hemolytic
      serum, but as the percentage was not appreciably altered, the difference depends
      presumably on variations in the bulk of feces rather than upon increased
      elimination. This evidence of the power of the body to conserve the iron
      rephagocytosis is negligible, is to be fragmented one by one, while still
      circulating, to a fine, hemoglobin-containing dust. The cell fragments are
      rapidly removed from the blood, but their ultimate fate remains to be determined.
      The facts indicate that they are removed from the blood by the spleen, and under
      exceptional conditions, by the bone marrow.

PMID- 19868118
TI  - A STUDY OF THE ACIDOSIS, BLOOD UREA, AND PLASMA CHLORIDES IN URANIUM NEPHRITIS IN
      THE DOG, AND OF THE PROTECTIVE ACTION OF SODIUM BICARBONATE.
AB  - 1. The presence of an acidosis in dogs with experimental uranium nephritis is
      demonstrable by the Van Slyke-Stillman-Cullen method and that of Marriott. It is
      detected more readily by the former method. 2. This acidosis is associated with
      increase in the blood urea and plasma chlorides and with the appearance of
      albumin and casts in the urine. 3. The oral administration of sodium bicarbonate
      diminishes the acidosis, the increase in plasma chlorides, the amount of albumin
      and casts in the urine, and, to a lesser degree, the increase in the blood urea
      following the administration of uranium. It also diminishes the severity of the
      changes produced by uranium in the kidneys. 4. The oral administration of sodium
      bicarbonate to normal dogs raises the carbon dioxide content of the plasma as
      determined by the. Van Slyke-Stillman-Cullen method.

PMID- 19868119
TI  - CICATRIZATION OF WOUNDS : IV. MATHEMATICAL STUDY OF THE EXTRAPOLATION FORMULA AND
      OF THE CURVE OF CICATRIZATION.

PMID- 19868120
TI  - THE DIGITALIZED DOG'S HEART AS AFFECTED BY AMYL NITRITE OR ATROPINE, STUDIED
      ELECTROCARDIOGRAPHICALLY.
AB  - The Effects of Strophanthin and of Digitalis. 1. In intact dogs the dose which
      caused slowing and other signs of vagus stimulation without causing ectopic
      contractions usually lay between 30 and 40 per cent of the minimum lethal dose
      for Thoms g-strophanthin and for digipuratum and a fluid extract of digitalis,
      given intravenously in dilute solution in about 15 minutes. 2. In dogs
      strophanthin and digitalis when given intravenously produced typical alterations
      in the electrocardiogram almost immediately and with equal rapidity. 3. In this
      series the changes in the electrocardiogram following the administration of 25 to
      40 per cent of the minimum lethal dose of strophanthin or digitalis often passed
      off within an hour or two and with few exceptions were not visible in
      electrocardiograms taken 20 hours later. The effects of digitalis did not appear
      to be more lasting than those of strophanthin. As there were marked differences
      in the persistence of the action of each of these drugs within its own series,
      this conclusion is provisional. 4. A persistent auriculoventricular block
      (without the occurrence of ectopic beats) was obtained only exceptionally, but
      the administration of 30 to 40 per cent of the minimum lethal dose of either of
      these drugs was usually followed by the occurrence either singly or together of
      occasional auriculoventricular blocks or exaggerated sinus arrhythmia or sinus
      block, and by pronounced slowing of the sinus rate. 5. Occasionally, with or
      without previous slowing or the occurrence of ectopic beats, these doses caused a
      marked acceleration of the sinus rate. 6. The auriculoventricular (P-R) time was
      usually lengthened but may be shortened. 7. The P wave may become less positive,
      isoelectric, or negative. 8. The T wave most often became negative before or
      during the stage of slowing but frequently became or remained positive during
      this stage. When the sinus rate increased or when occasional ectopic beats
      occurred, this wave almost always became decidedly more positive. At times it
      varied rapidly and decidedly within a period of a few seconds. 9. Ectopic
      ventricular beats occurred in a number of instances after doses ranging from 19
      to 40 per cent of the minimum lethal dose, and usually but not always when more
      than 40 per cent had been injected within 15 to 30 minutes. 10. Previous
      administration of either of these drugs did not appear to cause either a
      quantitative or qualitative alteration in the reaction of the heart to amyl
      nitrite or atropine (with the exception that such previous administration
      appeared responsible for the fact that in one experiment the inhalation of amyl
      nitrite, and in two others the injection of atropine, was followed by the
      occurrence of ectopic beats). The Effects of Amyl Nitrite. 1. In intact dogs,
      both before and after the administration of strophanthin or of digitalis, the
      inhalation of amyl nitrite usually caused at first (probably largely reflexly) a
      pronounced increase of vagus tone shown by slowing of the sinus rate) exaggerated
      sinus arrhythmia, or auriculoventricular block. Later the sinus rate was
      accelerated and arrhythmia or blocks disappeared (probably due to vasodilatation
      and diminished vagus tone). 2. The auriculoventricular (P-R) time was usually
      lengthened at first and later was shortened. 3. The P wave often at first became
      shorter, isoelectric, or negative, but later became much more positive. 4. The T
      wave at first often became less positive or more negative, but later became
      strongly positive. 5. When the previous administration of not too large doses of
      strophanthin or digitalis caused the occurrence of ectopic ventricular beats, the
      inhalation of amyl nitrite usually caused their temporary disappearance. Even
      when large doses of these drugs caused a constant succession of ectopic
      contractions of various types, its inhalation was often followed by a temporary
      return of nomotopic cycles or by a change in the form of the ventricular
      complexes so that they more closely resembled that of nomotopic ones. 6. Only
      large amounts of amyl nitrite appear to have the power to prevent ectopic
      ventricular beats or to alter their type. The Effects of Atropine. 1. In intact
      dogs before and after the administration of strophanthin or digitalis, smalf
      doses of atropine usually caused auriculoventricular block (or exaggerated it if
      already present). Larger doses, after first producing the same effect as the
      small ones, caused an increased sinus rate and abolished blocks or sinus
      arrhythmias if present. 2. The P-R time was usually lengthened by small doses and
      shortened by larger ones. 3. The P wave sometimes became shorter at first (less
      positive), isoelectric, or negative, but later (when the peripheral vagus
      paralysis ensued) it became positive again, often much more so than it was
      originally. 4. When ectopic contractions were present as a result of previous
      administration of strophanthin or digitalis, atropine, like amyl nitrite, often
      caused their disappearance, or altered the form of the ventricular complex, but
      was less efficient in this direction than amyl nitrite. 5. Occasionally the
      injection of atropine into dogs, which had previously received strophanthin or
      digitalis, appeared to facilitate or bring on the occurrence of ectopic
      ventricular contractions.

PMID- 19868121
TI  - SPIROCHAETA ICTEROHAEMORRHAGIAE IN AMERICAN WILD RATS AND ITS RELATION TO THE
      JAPANESE AND EUROPEAN STRAINS : FIRST PAPER.
AB  - The principal points brought out in the present article are the following. 1.
      Wild rats captured in this country carry in their kidneys a spirochete which
      possesses the morphological and pathogenic properties characteristic of
      Spirochata icterohamorrhagia discovered by Inada in the Japanese form of
      infectious jaundice. 2. Cultures of the American, Belgian, and Japanese strains
      of the spirochete were obtained by a special technique described, the first two
      strains having been cultivated artificially for the first time. 3. Animals
      actively immunized against the Japanese strain resist inoculation, not only of
      the same strain, but also of the Belgian and American strains. The Belgian strain
      produces immunity equally effective against all three strains. Experiments to.
      ascertain whether the immunity afforded by the American strain also protects
      against the Japanese and Belgian strains are in progress. 4. These findings
      warrant the conclusion that the spirochetes designated here as the Japanese,
      Belgian, and American strains are probably identical. 5. On account of its
      distinctive features, a new genus, Leptospira, has been suggested as the
      designation of this organism.

PMID- 19868122
TI  - IMMUNOLOGICAL STUDIES ON PURE CULTURES OF VARIOUS SPIROCHETES.
AB  - Experiments were carried out for the study of culture spirochetes in their
      relation to various immunity reactions in vitro. Several strains of Treponema
      pallidum and one each of Treponema calligyrum, Spirochata refringens, Treponema
      microdentium, and Treponema mucosum were used. Tests were made of immune
      substances responsible for agglutination, complement fixation, spirocheticidosis,
      and opsonization. In cases of agglutination and complement fixation, cross
      titrations were made. 1. In the sera derived from rabbits immunized with various
      spirochetes agglutinins were demonstrated in varying quantities for the
      homologous antigens. The amounts of agglutinins developed were considerably
      higher in the pallidum immune sera than in the other groups. There was no
      parallelism between the amounts of antigens injected and the amounts of
      agglutinins developed. 2. Cross titrations among different pallidum strains
      revealed that the agglutiantion is not necessarily strongest when homologous
      antigens and immune sera are brought together. 3. On the other hand, the
      reactions between the immune sera and antigens belonging to different species
      were sufficiently specific to justify the grouping. 4. Certain degrees of group
      reactions were observed between the pallidum immune sera and the calligyrum, and
      occasionally very faintly also between the pallidum and the refringes antigens
      and vice versa. There was a much more pronounced group reaction between the
      calligyrum and refringes. The immune serum and antigen of the microdentium showed
      a slight affinity for the mucosum but none for the pallidum, calligyrum, or
      refringes, while the mucosum immune serum caused a slight agglutination with many
      members of the other groups. Hence, it appears that the pallidum is more or less
      related to the calligyrum, while the affinity between the calligyrum and
      refringes, and possibly also between the calligyrum and mucosum in a much smaller
      degree, seems close. The microdentium showed the least relation to any other
      spirochetes. 5. Titration of agglutinins in the sera obtained 3 months after the
      cessation of immunization revealed that the agglutinin contents were already
      greatly reduced, having fallen roughly to 0.01 of the original strenght. The
      rates of disappearance were irregular in different animals and bore no direct
      relation to the initial titers. Titration made of the immune sera which had been
      preserved aseptically in a refrigerator (6 degrees C.) during the same period (3
      months) indicated that the original strength of these sera was reduced to about
      one-tenth. The agglutinins for spirochetes disappear from the rabbit's body much
      more rapidly than they are reduced in the separated sera by deterioration on
      standing at 6 degrees C. 6. Titration of the immune sera for complement fixation
      power showed with a few exceptions, in which there was only slight complement
      binding, that the titers were high enough to indicate the presence of this
      principle. The anti-pallidum sera possessed higher average titers than the other
      immune sera tested with correspondingly homologous antigens. The least active
      were the anti-refrigens sera. 7. Cross titration of anti-pallidum immune sera for
      complement fixation showed that a given serum with a high titer for its own
      strain of antigen was also strong with most of the other strains of the pallidum.
      Instances occurred also in which the titers with heterologous pallidum antigens
      fell far below those of the homologous. Group reactions between the different
      spirochetes) such as the pallidum and the calligyrum, the calligyrum and the
      refringens, and the microdentium and the mucosum, were also indicated. The
      mucosum and the pallidum showed a slight degree of group reaction. No anti
      pallidum serum fixed complement with the microdentium. 8. The immune sera were
      tested for their spirochetiddal properties in vitro against the correspondingly
      specific and heterologous varieties with and without the addition of complement.
      Many of the anti-pallidum sera killed their own strains. Normal rabbit serum
      exhibited only a slight degree of inhibition. Without complement, the immune sera
      caused a considerable reduction in the number or density of colonies, but not a
      complete suppression of growth. Complement alone had no injurious effect upon the
      pallidum strains. The antisera for the calligyrum, refringens, and mucosum showed
      feeble spirocheticidal action, while the antisera for microdentium was stronger.
      A syphilitic rabbit serum tested against a strain of culture pallidum gave a
      feeble inhibitory effect. 9. Under the influence of immune sera and complement,
      the spirochetes undergo within a few hours complete disintegration or granular
      degeneration. Without complement, they are more powerfully agglutinated, but no
      disintegration occurs, even after 20 hours, and complement alone has no effect.
      10. In the presence of homologous immune serum and complement, the culture
      pallidum may be ingested by the leukocytes, but phagocytosis is slight, possibly
      on account of the filamentous nature of the organisms. The spirochetes in such a
      mixture disintegrate within a few hours, disintegration being especially rapid
      when the immune leukocytes are used. In the absence of immune serum, phagocytosis
      is not noticeable, while without complement but in the presence of immune serum
      and leukocytes, some phagocytosis, without subsequent lysis, occurs. A virulent
      strain of pallidum, obtained from syphilitic orchitis in a rabbit, exposed to
      agglutination, lysis, and phagocytosis by an immune serum prepared by means of
      culture pallidum strains, showed only slight agglutination and phagocytosis but
      rapid immobilization without disintegration in the presence of complement.

PMID- 19868123
TI  - A CONTRIBUTION TO THE BACTERIOLOGY OF ACUTE ANTERIOR POLIOMYELITIS.
AB  - Four different varieties of easily cultivated microorganisms have been cultured
      from the cerebrospinal fluid and tissues of cases of acute anterior
      poliomyelitis; namely, a streptococcus, a diplococcus, diphtheroids, and Gram
      negative bacilli. It is not contended that they were all inherent in the tissues;
      a part were doubtless extraneous. The streptococci and diplococd may be
      considered as the most significant of the bacteria cultivated and are
      distinguishable from each other by biological tests. The streptococci grew both
      aerobically and anaerobically; under anaerobic conditions growth was slow, the
      cocci became small and round, and were more easily decolorized with alcohol in
      the Gram stain. They were not found in the anaerobic cultures of 106
      cerebrospinal fluids; they were found in one of twenty anaerobic blood cultures
      and frequently in the cerebrum, cerebellum, pons and medulla, cord, tonsils,
      lungs, liver, kidneys, spleen, pancreas, thymus gland, suprarenal glands, and
      mesenteric glands of fatal cases. The diplococci are Gram-positive and,
      transplanted to solid media, yield luxuriant growths and a staphylococcus
      grouping. They grew aerobically and anaerobically, but more slowly under the
      latter condition, and the cocci became smaller and more rounded. Diplococci were
      found in the anaerobic cultures of 48 of 106 cerebrospinal fluids; also in the
      cerebrum, cerebellum) pons and medulla, cord, tonsils, lungs, liver, kidneys,
      spleen, pancreas, and mesenteric glands of fatal cases. The filtrates of
      emulsions of tissues containing streptococci and diplococci passed through fine
      Kitasato and Pasteur-Chamberland filters were sterile unless large amounts of
      filtrates were collected. The amount of filtrate collected and cultured is
      therefore of considerable importance in filtration experiments. The small forms
      of streptococci and diplococci in old anaerobic cultures are filterable with
      these filters, while young aerobic cultures containing large forms are not,
      unless large amounts of culture are filtered. Intracranial, intravenous, and
      intraperitoneal injection of these easily cultivated streptococci, diplococci,
      diphtheroids, and Gramnegative bacilli failed to produce paralysis in rabbits or
      monkeys. With two exceptions all the cultures were transplants from the original
      anaerobic ascites-broth-kidney cultures of cerebrospinal fluid and various
      tissues. Arthritis and meningitis were produced by the streptococci, but there
      were neither clinical iior histological evidences of true poliomyelitis.
      Occasional bacteriological studies since 1898 have shown that easily cultivated
      micrococci and bacilli may be present in the cerebrospinal fluid and tissues of
      the central nervous system of persons suffering with acute anterior
      poliomyelitis. The majority of bacteriologists have found the cerebrospinal
      fluid, blood, and nervous organs sterile. Opinions have varied in regard to the
      significance of the organisms and the micrococci in particular, but the consensus
      of opinion has been to the effect that they are secondary invaders and unable of
      themselves to produce poliomyelitis in the lower animals. After allowing for
      contaminations due to technical errors in securing specimens, the total number of
      observations indicates that easily cultivated micrococci occur sometimes in the
      brain and cord of persons suffering from epidemic poliomyelitis. Our studies have
      shown that they may be found not only in these locations, but also in the spleen,
      kidneys, suprarenal glands, and other organs. It is not known that they exert an
      influence in this disease, although they may possibly give rise to the production
      of antibodies) assuming their entrance not to be wholly agonal,as the cultures of
      streptococci are frequently of sufficient virulence to produce meningitis in
      rabbits and monkeys. Our experiments are in accord with those of other
      investigators who found that these microorganisms do not produce poliomyelitis in
      the lower animals, and are therefore in sharp contrast with the recent reports
      which would attribute an etiologic relationship of streptococi and allied
      organisms to that disease. At present this wide divergence of result cannot be
      accounted for, but it does not seem that it is possible for it to reside in any
      condition of the cultures employed by us as they were obtained from undoubted
      cases of epidemic poliomyelitis and inoculated in early generations. As regards
      these easily cultivatable microorganisms, we agree at present with those who
      regard them as secondary and probably terminal invaders rather than the actual
      etiologic agent of the disease.

PMID- 19868124
TI  - HENLE'S REACTION OF THE CHROMAFFIN CELLS IN THE ADRENALS, AND THE MICROSCOPIC
      TEST FOR ADRENALIN.
AB  - We have established the fact that the chrome reaction as well as the silver and
      osmium reactions are merely reductions by adrenalin. In our opinion the naming of
      the cells giving a positive reaction should not be based upon the reaction i.e.,
      chromaffin cells), but on the presence of adrenalin itself. Biedl's terms,
      adrenal cell, adrenal organ, adrenal body, adrenal system, and also Bonnamour's
      term, adrenalin-producing cells, are appropriate in this respect. We propose the
      names adrenalin cell, adrenalin tissue, adrenalin system, thereby indicating the
      presence of adrenalin.

PMID- 19868125
TI  - STUDIES ON BACILLUS WELCHII WITH SPECIAL REFERENCE TO GAS GANGRENE.
AB  - 1. Spores of the Bacillus welchii group of bacteria were found on 100 per cent of
      the uniforms of Belgian soldiers who had come directly from the trenches, and in
      the meshes of all the samples examined of the new cloth from which the uniforms
      were made. 2. In fifteen out of twenty fresh war wounds members of this group of
      bacteria were found. Of the fifteen patients, only three later developed gas
      gangrene. Once the spores of Bacillus welchii have been carried into a wound the
      deep-lying lacerated muscle tissue appears to be the most important factor in the
      onset of gas gangrene. 3. Bacillus welchii is able to grow and produce gas in
      broth containing up to 40 per cent saccharose. Some strains were able to multiply
      and produce gas in 50 per cent saccharose broth; but none of those examined were
      able to grow when the concentration of the sugar reached 60 per cent. 4. The
      bubbling of pure oxygen through milk or dextrose broth cultures of Bacillus
      welchii has a definite depressor action on the production of gas. This does not
      appear to be-due to a reduced number of organisms in the culture.

PMID- 19868126
TI  - EQUILIBRIA IN PRECIPITIN REACTIONS : THE COEXISTENCE OF A SINGLE FREE ANTIGEN AND
      ITS ANTIBODY IN THE SAME SERUM.
AB  - 1. In these studies several phases of the predpitm reactions were investigated by
      the use of purified proteins as antigens. These preparations were edestin from
      hemp-seed and crystalline ovalbumin from fresh eggs. The ovalbumin, isolated by
      the method of Hopkins and Pinkus,.was apparently as pure as is obtainable by
      chemical means. This albumin, however, produced moderately severe anaphylactic
      reactions in animals sensitized with ovoglobulin. Anaphylactic tests of the
      individuality of a protein cannot be any longer regarded as the criterion of the
      purity of the substance as an antigen. Wells and Osborne have shown that proteins
      of considerable chemical difference may have a common antigenic group which
      causes mutual anaphylactic reactions in animals sensitized to these proteins. In
      particular, as egg globulin is a mixture of proteins, one of which is undoubtedly
      egg albumin, anaphylaxis produced by injections of albumin into animals
      sensitized to the so called globulin offers no evidence for or against the purity
      of the albumin. The character of the curves shown in Text-fig. 1 confirms the
      assumption, based upon chemical data, that crystalline egg albumin is a single
      protein. 2. With edestin and crystalline egg albumin as antigens phases in the
      precipitin reaction were found in which these substances and their specific
      precipitins could be demonstrated to be coexistent but ununited in the same
      serum. 3. When edestin or crystalline egg albumin is injected into a rabbit
      immunized thereto, the antigen may be found in the circulating blood during 48
      hours after its injection, while at the same time the animal maintains a high
      titer of free precipitin in its blood. 4. When the pure protein antigen is mixed
      in proper proportions with the serum of a specifically immunized rabbit and the
      resulting precipitate removed by centrifugation, the supernatant fluid contains
      both antigen and antibody. 5. The serum drawn from a rabbit during the period in
      which free antigen and antibody are coexistent in the circulation undergoes slow
      spontaneous precipitation when kept in sterile tubes in the ice box. The curve of
      this reaction is reproduced as Text-fig. 1. The relationships of the parabola
      indicate that the interaction of antigen and antibody takes place according to a
      definite law. When sufficient quantitative data are obtained to allow an analysis
      of this curve, the formulas for this reaction will undoubtedly throw light upon
      the chemical or physical nature of the process. 6. The protective action of the
      solution of egg albumin as a third colloid preventing precipitation in a reaction
      between human serum and its antibody was readily demonstrated. This observation
      and the constancy of the long prozone in precipitin test with egg albumin are in
      accord with the protective action of ovalbumin upon colloidal gold.

PMID- 19868127
TI  - THE FOCAL PULMONARY TUBERCULOSIS OF CHILDREN AND ADULTS.
AB  - Evidence of tuberculous infection has been found in the lungs of all of fifty
      adults who have been examined. Approximately one-half of all adults have
      encapsulated lesions of the lungs or bronchial lymphatic nodes, whereas in one
      third pulmonary and lymphatic lesions are firmly calcified and completely healed.
      Tuberculous pulmonary lesions of adults who have died of diseases other than
      tuberculosis are of two types: (1) apical tuberculosis similar to the usual type
      of fatal phthisis and unaccompanied by caseation, of the regional lymphatic
      nodes; (2) focal tuberculosis not more commonly situated in the apices of the
      lungs than elsewhere and accompanied by caseation (or calcification) of the
      adjacent lymphatic nodes. Focal pulmonary tuberculosis of adults is identical
      with the tuberculosis of childhood. It occurs in at least 92 per cent of all
      adults. It may be acquired between the ages of 2 and 10 years but in more than
      half of all individuals (in this city) makes its appearance between the ages of
      10 and 18 years. Tuberculosis of children does not select the apices of the
      lungs, is accompanied by massive tuberculosis of regional lymphatic nodes, and
      exhibits the characters of tuberculosis in a freshly infected animal, whereas
      tuberculosis which occurs in the pulmonary apices of adults has the characters of
      a second infection. Almost all human beings are spontaneously "vaccinated" with
      tuberculosis before they reach adult life.

PMID- 19868128
TI  - A CLASSIFICATION OF NON-HEMOLYTIC STREPTOCOCCI.
AB  - 1. No connection can be demonstrated between grouping of non-hemolytic
      streptococci based upon fermentation reactions, and grouping based upon
      immunological reactions. 2. A classification of non-hemolytic streptococci can be
      effected by studying the complement fixation reactions between the streptococci
      and their antisera. 3. The arrangement of the streptococci in such a
      classification depends on the fact that two diverse elements are present in the
      group. Some strains partake entirely of one of these elements, some entirely of
      the other, while other strains partake of both. 4. The arrangement is further
      determined by the fact that among the strains composed of one element there are
      differences in complexity, some strains being made up of many molecules or
      features, others having much simpler structure. This gives rise to an inverse
      ratio between the fixing capacity of a serum and the capacity of the
      corresponding antigen to be fixed.

PMID- 19868129
TI  - A CONSIDERATION OF THE RELATIVE TOXICITY OF URANIUM NITRATE FOR ANIMALS OF
      DIFFERENT AGES. I.
AB  - 1. The toxic effect of uranium when given in a constant quantity per kilo of body
      weight is variable. This variation has been constantly associated with
      differences in the age of the animals. Uranium is more toxic for an old animal
      than for a young animal. The establishment of this fact, namely, that the age of
      an animal may modify the toxicity of a substance, should be taken into account in
      establishing by animal experiment the degree of activity of substances which are
      to be used for therapeutic purposes. 2. The toxic effect of uranium nitrate is
      constantly associated with its ability to induce a tissue acidosis. A severer
      grade of acidosis is induced in an old animal from uranium than is induced in a
      young animal. It would appear that in the response of dogs of different ages to
      uranium the animals represent a reaction system to this substance which shows an
      increasing susceptibility as the animal advances from youth to senility.
      Insufficient experimental data are as yet available to allow a discussion of the
      mechanism by which such an acid intoxication is produced. 3. The toxic effect of
      uranium is manifested locally by certain degenerative changes in the kidney.
      These changes are more marked in the kidney of an old animal than they are in the
      kidney of a young animal. Associated with the severer kidney changes which are
      especially characterized by a beginning swelling of the renal epithelium and by
      an accumulation of stainable fat in these cells is the development of a severe
      grade of tissue acidosis. 4. The functional capacity of the kidney shows a
      parallel with the degree of acid intoxication and with the severity of the
      histological changes which have developed in the renal epithelium.

PMID- 19868130
TI  - TOXIN AND ANTITOXIN OF AND PROTECTIVE INOCULATION AGAINST BACILLUS WELCHII.
AB  - Five cultures of Bacillus welchii have been studied and compared Four came from
      infected wounds in the western theatre of war, and one was obtained from a
      personal article of clothing. Each culture possesses the essential
      characteristics ascribed to that group of bacteria. The infectious processes
      caused by the five cultures in rabbits, guinea pigs, and pigeons, are local in
      character; and very few or no bacilli enter or are found in the general blood
      stream during life or immediately after death. Glucose broth cultures, injected
      intravenously, are fatal to rabbits. Death occurs, almost immediately or after a
      few hours. Agglutinative bacterial emboli have been ruled out as the cause of
      death, as has been an acid intoxication. The fluid part of the culture acts in
      the same manner as the full culture and irrespective of neutralization with
      sodium hydroxide. The full cultures and supernatant fluid are hemolytic when
      injected directly into the circulation of rabbits and pigeons, and the acute
      death produced may be ascribed to a massive destruction of red corpuscles. The
      passage of the fluid portion of glucose broth cultures through Berkefeld filters
      reduces materially the hemolytic and poisonous effects. Cultures of the Welch
      bacilli in plain broth to which sterile pigeon or rabbit muscle is added are
      highly toxic, and the toxicity is not noticeably diminished by Berkefeld
      filtration. The filtrates are hemolytic when injected intravenously and inflaming
      and necrotizing when injected subcutaneously and intramuscularly. The local
      lesions produced in the breast muscles of the pigeon closely resemble those
      caused by infection with the bacilli. The toxicity of these filtrates is not
      affected by neutralization with sodium hydroxide, but is materially reduced by
      heating to 62 degrees C. and entirely removed by heating to 70 degrees C. for 30
      minutes. Successive injections of carefully graded doses of this toxic filtrate
      in pigeons and rabbits give rise to active immunity. The blood taken from the
      immunized rabbits is capable of neutralizing the toxic filtrate in vivo and in
      vitro. The filtrate has therefore been designated as toxin and the immune serum
      as antitoxin. The antitoxin neutralizes the toxin in multiple proportions. Hence
      the latter would seem to possess the properties of an exotoxin. Moreover, it
      neutralizes the hemolytic as well as the locally .injurious toxic constituent.
      Antitoxic serum prepared from a given culture of Bacillus welchii is neutralizing
      for the toxins yielded by the other four cultures of that microorganism. The
      antitoxin is protective and curative against infection with the spore and the
      vegetative stages of Bacillus welchii in pigeons. The limits of the protective
      and curative action are now under investigation.

PMID- 19868131
TI  - THE EFFICIENCY OF VARIOUS DIURETICS IN THE ACUTELY NEPHROPATHIC KIDNEY, PROTECTED
      AND UNPROTECTED BY SODIUM CARBONATE. II.
AB  - The outline which has been given of the relative toxicity of Grehant's anesthetic
      in normal animals, in animals that were nephropathic from uranium and protected
      against the anesthetic by an alkaline solution, and in those animals which were
      unprotected by such a solution, furnishes the basis for the following summary.
      The kidney of the normal dog is relatively non-susceptible to the toxic action of
      Grehant's anesthetic. The kidneys have failed to show any change in their
      histological structure during the period of anesthesia. These animals have
      remained diuretic during the period of anesthesia and have responded to diuretics
      such as theobromine, pituitrin, and solutions of urea and sodium chloride. Normal
      animals anesthetized with Grehant's mixture for 1(1/2) hours usually show at the
      end of the experiment either no change, or only a slight variation from the
      normal, in the hydrogen ion content of the blood, the alkali reserve of the
      blood, and in the tension of carbon dioxide. In several normal dogs which were
      over 4 years of age, by the end of an anesthesia of such a duration the animals
      have shown a reduction in the alkali reserve of the blood and also a decrease
      from the normal in the carbon dioxide tension of alveolar air. From this
      observation it would appear that even in a normal animal Grehant's anesthetic
      tends to induce an acid intoxication, and as was the case with normal animals
      which were being intoxicated by uranium, such an intoxication is more readily
      induced in an old animal than in a young one. The nephropathic animals which have
      been anesthetized by Grehant's anesthetic and in which an attempt has been made
      to protect these animals against the toxic effect of the anesthetic by the use of
      asolution of sodium carbonate fall into two clear-cut groups. Those animals of
      the series not over 1(1/2) years old have shown at the end of the uranium
      intoxication and prior to the use of the anesthetic a less severe acid
      intoxication than have the animals of the series which were over 1(1/2) years
      old. In this younger group of animals the intravenous injection of a 3 per cent
      solution of sodium carbonate immediately before the animals were anesthetized has
      succeeded in protecting these animals against the toxic action of the anesthetic.
      During the following 1(1/2) hours of anesthetization these animals have not
      developed a severe grade of acid intoxication, and in several of the animals at
      the end of the experiment the alkali reserve of the blood was in excess of what
      it was at the end of the uranium intoxication and before an anesthetic was
      administered. Animals of this protected group have remained diuretic throughout
      the experiment and have shown an active diuresis from pituitrin, theobromine, and
      solutions of urea and sodium chloride. The kidneys of such animals have shown
      histologically a normal vascular tissue, a convoluted tubule epithelium which
      gave the appearance of being hyperactive, and only occasionally were tubules
      encountered which showed signs of an early epithelial degeneration. The
      nephropathic animals of the series in which a solution of sodium carbonate failed
      to afford any protection against Grehant's anesthetic were animals over 1(1/2)
      years old in which the uranium intoxication had resulted in a severer grade of
      add intoxication than in the younger animals. When these older animals were given
      intravenously the carbonate solution and were anesthetized, it was found
      impossible to increase the alkali reserve of the blood to the same extent as was
      possible in the younger animals. Furthermore, the alkaline solution during the
      period of anesthesia is rapidly used up so that by the termination of these
      experiments the animals may have an alkali reserve of the blood which may be even
      lower than was the alkali reserve before the use of the carbonate. These animals
      have remained completely anuric throughout the experiments and have shown no
      diuretic effect from those diuretics which in the animals that were successfully
      protected by the carbonate induced free diuresis. The kidneys of these anuric
      animals show no degenerative changes in the glomerular vessels. The capillaries
      are not distended with blood as has been the case with the diuretic group. The
      epithelium of the convoluted tubules is acutely swollen. The swelling has
      frequently taken place to such an extent that the lumen of the tubules has become
      obliterated. The nephropathic animals of the series which served as control
      animals and which were given a solution of sodium chloride equimolecular with the
      carbonate solution, following Grehant's anesthetic became completely anuric. The
      sodium chloride solution furnished no protection against the anesthetic. The
      animals of all ages became anuric and unresponsive to the diuretic substances
      which have been used during this study. With the establishment of a state of
      anuria in these control animals the hydrogen ion content of the blood has
      increased, the alkali reserve of the blood has been rapidly depleted, and
      associated with this change the carbon dioxide tension has been reduced. The
      rapidity with which these changes develop and the degree of acid intoxication
      which is induced is more marked in these animals than in any of the other series.
      The kidneys of the control animals show the severest grade of degeneration of any
      of the nephropathic animals. The epithelium of the convoluted tubules is not only
      severely swollen but the cells frequently show necrosis. The loops of Henle
      contain more stainable fat than has been demonstrated in the kidneys of the
      carbonate animals.

PMID- 19868132
TI  - CULTIVATION OF SPIROCHAETA OBERMEIERI.

PMID- 19868133
TI  - A VALVE TO REGULATE THE DELIVERY OF AIR AND ETHER VAPOR IN ANY PROPORTION.
AB  - A valve is described for the control of ether vapor for anesthesia which
      regulates the mixture of ether vapor from a Woulfe bottle with air in any
      proportion, without changing the volume or the pressure at which the mixture is
      delivered. The regulation of the air stream both to and from the ether bottle
      controls the mixture accurately and is an essential feature of the valve. Except
      for experimental purposes, it is not considered profitable to determine on an
      arbitrary scale the tension of the ether vapor obtained, because the depth of the
      anesthesia should always be judged by the condition of the subject. The valve was
      devised for the Meltzer-Auer method of intratracheal insufflation, but it is
      adapted for use wherever a constant mixture of air and ether vapor is desired.
      Several respiration machines for supplying and interrupting the air stream, using
      this constant volume valve for the regulation of the ether supply, have been in
      use in Dr. Meltzer's laboratory for periods up to 2 years, and the simplicity and
      efficiency of the valve have been thoroughly tested. A description of the
      complete machine will be published later.

PMID- 19868134
TI  - THE RELATION OF MOSQUITOES AND FLIES TO THE EPIDEMIOLOGY OF ACUTE POLIOMYELITIS.
AB  - 1. Culex pipiens raised from the larval stage in water experimentally
      contaminated with an abundance of poliomyelitic virus were found to be incapable
      of causing the infection when allowed in large numbers to bite normal Macacus
      monkeys. 2. Culex pipiens which were fed on infected poloimyelitic monkeys during
      different stages of the disease were found to be incapable of transmitting the
      infection when allowed in large numbers to bite normal Macacus monkeys. A
      previous disturbance of the meninges by an injection of horse serum into the
      intrathecal space did not alter the result, which was negative. 3. The offspring
      of the mosquitoes which were either reared in the infected tanks or fed on
      infected monkeys were found to be entirely harmless when allowed to feed in large
      numbers on a normal monkey. There was no hereditary transmission of the virus
      from one generation to another. 4. No trace of the virus of poliomyelitis was
      demonstrable in the filtrate of an emulsion of adult flies and pupae of the
      common housefly and bluebottle fly which were reared in the laboratory on slices,
      emulsion, or filtrate of monkey brain containing the poliomyelitic virus. The
      intracerebral injection of the filtrate produced no poliomyelitic infection in
      the normal monkey.

PMID- 19868135
TI  - NEW ANAEROBIC METHODS.
AB  - 1. Anaerobic methods have been devised which depend upon the catalytic action of
      platinized asbestos upon hydrogen and oxygen. 2. The methods may be utilized for
      the growth of anaerobes in test-tubes, upon Blake bottles, in flasks, and in a
      large container. 3. Because oxygen is so completely removed, the methods are of
      great value in the successful cultivation of absolute anaerobes.

PMID- 19868136
TI  - METHODS FOR THE DETERMINATION OF PNEUMOCOCCUS TYPES.
AB  - The determination of pneumococcus types in lobar pneumonia is of value in the
      field of prognosis and as a prerequisite for specific serum therapy. The method
      for the determination of types should be as rapid as possible and a standard
      technique should be employed. The most satisfactory method is by the
      intraperitoneal inoculation of a mouse with the patient's sputum, by which means
      a rapid and abundant growth of the pneumococcus is obtained and secondary
      organisms are rapidly eliminated in most instances. The diagnosis of type is made
      directly on the peritoneal exudate. Certain factors in the method commonly used
      have interfered with the rapid determination of types in an appreciable number of
      cases, notably the growth of other organisms in the peritoneal exudate together
      with the pneumococcus, and some confusion has arisen because occasional strains
      of pneumococci have been encountered that show cross agglutination reactions when
      undiluted immune serum is used. Such reactions have been shown to be due to a
      limited zone of non-specific immunity and they in no way invalidate the
      classification of the pneumococci into sharply defined immunological groups. The
      optimum dilutions of serum have been determined that will agglutinate all type
      strains of pneumococci and fail to cause any cross agglutination reactions when
      mixed with equal amounts of pneumococcus cultures and incubated for I hour at 37
      degrees C. They are a 1:20 dilution of Serum I, a 1:20 dilution of Seruifa II,
      and a 1:5 dilution of Serum III. For the diagnosis of Subgroup II pneumococci
      undiluted Type II serum is required. To obviate the other difficulties of the
      method commonly used a new method for the determination of types has been
      devised. It depends upon the fact that there is produced by the growth of the
      pneumococcus a soluble substance which is present in the peritoneal exudate of
      the mouse in sufficient quantity to give a specific precipitin reaction with the
      homologous immune serum. The precipitin method can be used in all instances in
      which the determination of types by the agglutination method is possible, and it
      possesses certain distinct advantages which make it available when the
      agglutination method is impracticable. It is of particular value as a time-saving
      device in those instances where the presence of other organisms together with the
      pneumococcus in the peritoneal exudate causes a delay of 18 hours or more before
      the type of pneumococcus can be definitely established. It is therefore
      recommended as the method of choice in all cases. If desired, both the
      agglutination and precipitin methods may be applied to the same specimen of
      peritoneal washings.

PMID- 19868137
TI  - CICATRIZATION OF WOUNDS : V. NEW MATHEMATICAL EXPRESSION OF CICATRIZATION.

PMID- 19868138
TI  - CICATRIZATION OF WOUNDS : VI. BACTERIOLOGICAL ASEPSIS OF A WOUND.
AB  - Of twenty infected cases treated with Dakin's solution or chloramine paste, seven
      were bacteriologically sterile. This proves that, in general, 35 per cent of the
      cases thus treated become bacteriologically aseptic. This degree of asepsis is
      not necessary in order to suture the wound, the absence of bacteria in films
      being sufficient. Complete sterilization of wounds, can, therefore, now be
      accomplished.

PMID- 19868139
TI  - CICATRIZATION OF WOUNDS : VII. THE USE OF CHLORAMINE-T PASTE FOR THE
      STERILIZATION OF WOUNDS.
AB  - Dakin's toluene sodium p-sulfochloramide, mixed with sodium stearate, forms a
      paste sufficiently active and stable to be used in the treatment of wounds.

PMID- 19868140
TI  - CICATRIZATION OF WOUNDS : VII. STERILIZATION OF WOUNDS WITH CHLORAMINE-T.
AB  - Sodium stearate has no effect upon the bacteriological condition of a wound, but
      the addition of 4 parts per 1,000 of chloramine-T renders it antiseptic.
      Experiment I enabled us to compare the action of sodium stearate alone with that
      of sodium stearate containing 4 parts per 1,000 of chloramine-T. Wounds which had
      been previously sterilized could be maintained in an aseptic condition by 4 parts
      per 1,000 of chloramine-T, although in some cases reinfection occurred
      (Experiments 2, 3, and 5). For this reason the concentration of chloramine-T was
      increased. Surface wounds, deep-seated wounds, and osseous cavities, which had
      previously been either completely or almost completely sterilized, could be
      maintained for days and even weeks in a condition of surgical asepsis by the use
      of a paste containing 7 and 10 parts per 1,000 of chloramine-T. Experiments 7, 8,
      9, 10, and 12 are examples of this. Slightly infected wounds (Experiments 9, II,
      and 12) were sterilized in the same manner. Next, it was attempted to sterilize
      wounds which were suppurating and more or less infected, and in some cases
      accompanied by fracture. This attempt was probably successful because the wounds
      used for the experiments showed but slight quantities of secretions and only a
      shallow layer of necrotic tissue. It is useless to attempt to sterilize severely
      infected wounds with a paste, for the volume of chloramine-T that can be applied
      is too limited. A large volume of an active substance is required to sterilize a
      wound which secretes great quantities of pus, for owing, on the one hand, to the
      dilution of this substance with the secretions, and, on the other, to its
      combination with the proteins contained in the pus, the concentration of the
      antiseptic is rapidly diminished. For these reasons it is essential that the
      antiseptic solution should be constantly renewed, so that the concentration may
      be sufficiently strong to effect the destruction of the bacteria. Therefore, the
      chloramine-T paste cannot sterilize a severely infected wound. The concentration
      of the active substance contained in a paste must at the same time be
      sufficiently weak to be innocuous to the tissues. We have seen that it should not
      exceed 15 parts per 1,000. Thus, it is evident that if the secretions from the
      wounds are abundant, the substance could exert its action upon the microorganisms
      for the space of only a few hours. For this reason the chloramine paste should
      only be applied under the conditions specified in our experiments; that is, in
      connection with moderately infected wounds which have been carefully washed with
      sodium oleate, and possess but slight quantities of secretion. Under these
      conditions, the chloramine paste effects the complete disappearance of the
      bacteria and maintains the sterility thus secured for as long a time as may be
      wished. If the technique followed in the dressing is not exactly as above
      described, reinfection will occur. If applied in this manner the chloramine paste
      is not injurious to the tissues, for the cicatrization curves of the wounds thus
      treated show but slight modification from the calculated curves. Chloramine paste
      makes it possible, therefore, to keep wounds sufficiently free from
      microorganisms so that the effect of substances which are believed to influence
      cicatrization can be studied.

PMID- 19868141
TI  - STUDIES IN GLOMERULONEPHRITIS : I. A QUANTITATIVE STUDY OF THE REACTION OF THE
      KIDNEY TO DIPHTHERIA TOXIN.
AB  - 1. Diphtheria toxin of known strength, injected intravenously into rabbits in
      single doses, produces lesions which are first evident in the endothelium of the
      tufts, and possibly in the intertubular capillaries. 2. The lesions of greatest
      severity with medium doses are also found in the tufts. 3. Evidence is presented
      to show that epithelial damage in the tufts and especially in the tubules is
      secondary to the vascular injury. 4. The severity of the lesions was roughly
      proportional to the amount of toxin injected. Hemorrhages did not occur with
      doses of less than 0.0023 cc. of toxin per kilo of body weight and were not
      extensive with doses of less than 0.004 cc. per kilo. 5. It is suggested that the
      localization of lesions in the tufts is due to the concentration of toxin in the
      blood that follows the loss of water at this point. 6. It is further suggested
      that this inference may be extended to explain the pathogenesis of the so called
      intracapillary form of glomerulonephritis.

PMID- 19868142
TI  - STUDIES IN GLOMERULONEPHRITIS : II. A FORM OF ACUTE GLOMERULONEPHRITIS PRODUCED
      WITH DIPHTHERIA TOXIN AND BACILLUS COLI.
AB  - 1. Rabbits in which a mild grade of glomerular damage has been produced by small
      doses of diphtheria toxin develop a severe glomerulonephritis corresponding to
      the extracapillary form described by Volhard and Fahr after inoculations with
      sublethal quantities of Bacillus coli. 2. Similar, though not completely
      identical lesions are produced when diphtheria toxin is followed by intravenous
      injections of Vaughan's split protein (poisonous part) of Bacillus coli. 3. The
      inference is drawn that under the experimental conditions described Bacillus coli
      undergoes bacteriolysis and produces glomerular lesions through the toxic groups
      contained within its protein molecule.

PMID- 19868143
TI  - EXPERIMENTAL STUDIES UPON LYMPHOCYTES : II. THE ACTION OF IMMUNE SERA UPON
      LYMPHOCYTES AND SMALL THYMUS CELLS.
AB  - The work of previous investigators gives the impression that it is easy to
      produce sera which both in vitro and upon injection are leukotoxic. At the same
      time the specificity of these leukotoxic sera for the particular type of cell
      used as antigen, and even for leukocytes in general, has been doubtful. The
      methods used have made certain possible factors of error unavoidable. Even
      careful washing of an organ or suspension cannot render it wholly blood-free, so
      that it is not surprising that the sera should be moderately hemolytic and
      hemagglutinative. Pearce has shown that the injection of very small amounts of
      blood is sufficient to evoke the production of immune hemolysins. When such sera
      are injected the lesions, as Pearce states, may be due in part to the production
      of hemagglutinative thrombi, although this hardly seems to apply to the changes
      in lymphoid tissue described by Flexner. On the other hand, the lymphotoxic
      effect of hemolytic sera may be due to the lymphocytes injected with the red
      cells. Our own experiments indicate that the lymphotoxic and agglutinative
      factors are to a considerable degree distinct from the hemolytic and
      hemagglutinative ones, since they can be separated from one another by
      absorption. Further evidence is presented that the small thymus cells are
      biologically related to, if not identical with the lymphocytes derived from lymph
      glands.

PMID- 19868144
TI  - THE MECHANISM OF UREA RETENTION IN NEPHRITIS.
AB  - 1. Urea retention, in the sense of a relatively increased concentration in the
      blood, is the result of increased resistance to the excretion of urea through the
      kidneys. 2. The relatively increased concentration of urea in the blood overcomes
      the increased resistance to excretion, and the organism is thereby maintained in
      nitrogenous equilibrium. 3. The laws formulated by Ambard for the excretion of
      urea apply in the condition of urea retention under a widely varying range of
      conditions, as to nitrogen intake and excretion. 4. The numerical value of
      Ambard's constant changes in urea retention, but the relation of the variable
      factors to one another remains otherwise unchanged. 5. In certain individuals,
      with otherwise normal findings in regard to urea excretion, an unusual degree of
      constancy, to which we have applied the term fixation, has been found in the
      numerical results obtained by the application of Ambard's laws. These individuals
      are regarded, as the result of this study, as probably abnormal, but the
      pathological significance of the fixation has not been determined.

PMID- 19868145
TI  - EXPERIMENTS ON THE CAUSATION AND AMELIORATION OF ADRENALIN PULMONARY EDEMA.
AB  - The intratracheal injection of one moderate dose of adrenalin in rabbits whose
      vagi are divided produces a marked pulmonary edema in a large percentage of
      cases. The same dose in normal animals causes only slight effects. Artificial
      respiration greatly reduces the production of pulmonary edema in vagotomized
      rabbits after adrenalin. As adrenalin can exert a bronchoconstrictor effect,
      evidence is submitted to show that the aspirating action of the lung alveoli
      under this condition apparently plays an important part in the production of
      adrenalin pulmonary edema. On the basis of this mechanism the protective action
      of artificial respiration is explained. Stenosis of the trachea facilitates. the
      production of adrenalin pulmonary edema in rabbits whose vagi are intact. The
      intratracheal injection of adrenalin in vagotomized rabbits produces a temporary
      incoordination between the heart ventricles, visible on inspection, so that the
      left ventricle beats apparently half as fast as the right, causing hyperemia of
      the lungs and hemorrhages. Atropine injected intratracheally in vagotomized
      rabbits exerts a protective action against adrenalin pulmonary edema.

PMID- 19868146
TI  - THE EFFECTS OF EXPERIMENTAL PLETHORA ON BLOOD PRODUCTION.
AB  - With the purpose of determining whether a diminished activity of the bone marrow
      could be brought about experimentally, plethora was produced in rabbits by means
      of repeated small transfusions of blood. Counts of the number of reticulated red
      cells in the circulating blood were made during the course of the experiments as
      an index to changes in the activity of the bone marrow. With the development of
      plethora, the number of reticulated cells in the blood decreased. In the majority
      of the plethoric animals, this diminution was extreme, and in some instances,
      reticulated cells practically disappeared from the blood. A comparison of the red
      bone marrow of these animals with that of normal controls revealed a marked
      reduction in the content of reticulated cells. After a number of transfusions,
      there occurred in some of the plethoric rabbits a sudden and marked drop in
      hemoglobin. The hemoglobin continued to fall until a severe grade of anemia was
      reached. This was followed by an extremely rapid regeneration accompanied by a
      striking rise in color index. During regeneration, the reticulated cells were
      enormously increased in number. Taken together, these facts show that the bone
      marrow is markedly influenced by plethora. The diminished number of reticulated
      cells observed, both in the circulating blood and in the marrow, would make it
      appear that a decided decrease in blood production occurs. The reduction in the
      number of these cells cannot be due to changes in the constitution of the red
      cells put out by the bone marrow, as a result of an increased quantity of
      hemoglobin in the body, because during regeneration from the above mentioned
      anemia, when the color index was very high, reticulated cells were still present
      in large numbers. That the activity of the bone marrow does actually diminish
      during plethora is further evidenced by the occurrence of the anemia. The most
      reasonable explanation of this phenomenon is that the recipient develops an
      immunity against the blood of the donors, which results in the destruction of the
      strange cells that are in circulation. In keeping with this conception is the
      appearance of isoagglutinins for the donors' red cells in the blood of the
      recipient, at about the time of the beginning fall in hemoglobin. The occurrence
      of anemia as a result of the destruction of the alien blood only would seem to be
      due to the circumstance that, during the period of plethora, blood production is
      greatly diminished; as a consequence, the blood cells proper to the recipient are
      gradually reduced in number and replaced by alien cells until the latter come to
      constitute the bulk of the animal's blood. In those rabbits developing anemia,
      the initial drop of hemoglobin from the plethoric level to the normal was
      constantly accompanied by a marked rise in the number of reticulated cells. This
      brought up a subsidiary problem for study. With the idea that the stimulation of
      the bone marrow might be due to the presence of an increased quantity of broken
      down blood, rabbits, were injected intravenously with large amounts of laked
      blood cells. The procedure had no evident effect on the blood picture. It was
      then found that simple blood removal from a plethoric animal which brought back
      the hemoglobin to the normal level, or even to a point somewhat above, sufficed
      to cause a marked increase in the number of reticulated cells. Although these
      findings are not conclusive, they suggest an explanation for the increased bone
      marrow activity accompanying the initial drop of hemoglobin in the plethoric
      rabbits; namely, that the organism had in some way adapted itself during the
      period of plethora to the presence of a greater amount of blood and that the
      result of blood loss in such an organism was a relative but not absolute anemia.
      The finding that the activity of the bone marrow can be depressed by the
      introduction of a large quantity of blood into the circulation accounts for the
      diminished bone marrow activity which sometimes occurs after transfusion in
      pernicious anemia. In such cases there is a marked drop in the number of
      reticulated cells and other evidence of bone marrow depression; the patient shows
      no benefit from transfusion or may grow rapidly worse. The cause of this
      depression is best explained on the basis that in severe instances of the disease
      where exhaustion of the bone marrow is imminent, the stimulus of the anemia is
      only just sufficient to keep the marrow functioning. A sudden lowering of this
      stimulus is brought about by the introduction of a large quantity of blood into
      the circulation, and the result is a fall in the activity of the bone marrow. It
      follows from this that in pernicious anemia with a feebly reacting bone marrow as
      indicated by the number of reticulated red cells, small transfusions are
      preferable to large ones.

PMID- 19868147
TI  - EXPERIMENTAL STUDY OF ORGANIZATION IN LOBAR PNEUMONIA.
AB  - The experiments reported above give evidence that in unresolved lobar pneumonia,
      the persistence of the exudate, followed by organization, depends upon the
      presence of serum in the exudate.

PMID- 19868148
TI  - THE GROWTH OF THE OVARIAN FOLLICLE OF THE GUINEA PIG UNDER NORMAL AND
      PATHOLOGICAL CONDITIONS.
AB  - 1. The growth .energy of the granulosa cells in the ovarian follicles of normal
      guinea pig ovaries varies with the size of the follcle, and follows a definite
      growth curve. The growth energy in small follicles is relatively low, then a
      gradual rise takes place with increase in size of the follicle up to a maximum
      which is reached when the follicle attains medium size. This ascending part of
      the curve is followed by a gradual fall in growth energy until in large follicles
      the proliferative power has fallen almost to the level of small follicles.
      Synchronously with maturity of the follicles there is an abrupt fall in growth
      energy to near the zero point. 2. There is a distinct localization of mitoses in
      the follicle. The large majority of mitoses is found in the perioval part. With
      increase in the growth energy which characterizes medium follicles, there is an
      increase in the proliferative power of the cells more distal to the egg, but
      still near the egg. We may therefore conclude on the basis of our observations
      and on the previous observations of Loeb, that the egg exerts a stimulus, which
      causes proliferation of the granulosa cells. 3. Under pathological conditions
      certain changes occur in the growth energy of the follicle: (a) Granulosa
      degeneration causes in the living cells a diminution in the proliferative power
      which is proportionate to the extent of the degeneration. (b) Hypotypical
      follicles have approximately the same or only slightly diminished proliferative
      power as normal ones, and thus their failure to grow is essentially due to
      disintegration of the granulosa cells.

PMID- 19868149
TI  - THE RELATION OF APICAL TUBERCULOSIS OF ADULTS TO THE FOCAL TUBERCULOSIS OF
      CHILDREN.
AB  - The age incidence of focal tuberculous lesions of the lungs demonstrates that
      they have their origin in most instances in childhood. Focal lesions which heal
      have been found at all ages after the 2nd year of life, but in more than half of
      all individuals these lesions are acquired between the ages of 10 and 18 years.
      In the period between 18 and 30 years at least 85 per cent of all individuals
      have 'acquired focal tuberculous lesions. The occurrence of tuberculous infection
      in the lungs, in regional lymphatic nodes, or in some other organs of the body
      such as the gastrointestinal tract and its lymphatic system, is nearly universal
      but doubtless a few individuals escape. That focal tuberculous lesions of the
      lung are occasionally acquired during adult life is shown by the slight increase
      in the proportion of those with these lesions as age increases from 18 years to
      old age. Apical lesions of the lung make their appearance in later childhood and
      occur with increasing frequency from adolescence to old age (50 per cent). After
      the 2nd year of life focal tuberculous lesions occurring in situations other than
      the apices of the lungs tend to heal and after the 10th year focal lesions are
      almost invariably encapsulated and latent or healed. Fatal tuberculosis after the
      10th year is with few exceptions apical in origin. The apices are not only more
      susceptible to infection in later life but once infected afford less resistance
      to the extension of the lesion. The present series of cases has furnished
      opportunity to observe the character of the apical lesion in lungs of individuals
      previously infected with tuberculosis. With one exception the apical lesion (in
      eight instances) has pursued a chronic course and, encapsulated by fibrous
      tissue, has remained limited to the extreme apex of the lung. In one instance in
      a woman with advanced malignant disease chronic pulmonary tuberculosis has been
      progressive. Tuberculosis of the apices in those who have previously acquired a
      focal tuberculous lesion has pursued a chronic course and in most instances has
      remained latent or has completely healed. A very small group of instances of
      fatal pulmonary tuberculosis suggests that apical lesions in those who have not
      undergone previous infection may assume an unusually severe character. One
      instance of apical tuberculosis unaccompanied by focal lesions and followed by
      tuberculosis of the thoracic duct and disseminated miliary tuberculosis has been
      especially significant. Apical tuberculosis unaccompanied by evidence of
      preexisting tuberculosis may be accompanied by tuberculosis of the regional
      lymphatic nodes, whereas apical tuberculosis in an individual with a preexistent
      focal tuberculous lesion is not followed by tuberculosis of adjacent lymphatic
      nodes. It is well known that tuberculosis in previously uninfected animals is
      followed by tuberculosis of adjacent lymphatic nodes, whereas a second infection
      fails to implicate the regional lymphatic nodes. This relation has been well
      illustrated by the lungs of a monkey which acquired in confinement acute
      tuberculous pneumonia limited to the left lung; the lymphatic nodes on this side
      were greatly enlarged and caseous. The following observations indicate that
      apical tuberculosis of adults is not the result of infantile tuberculosis but is
      caused by subsequent infection: (a) Apical tuberculosis does not have its highest
      incidence, in accordance with common belief, in early adult life when focal
      infections acquired in childhood are relatively fresh and active but is more
      common in later life when the focal lesions of childhood have in most instances
      completely healed. It is noteworthy that most of these apical lesions of later
      life pursue a chronic course and are discovered at autopsy in individuals who
      have died from other causes. (b) The well characterized lesions of tuberculosis
      acquired in childhood and found in adults with apical lesions are almost
      invariably calcified and healed. The apical lesion is in most instances
      relatively fresh and caseous whereas the focal pulmonary lesion and associated
      lesions of regional lymphatic nodes exhibit no evidence of activity. (c) In a
      large proportion of instances of associated focal and apical tuberculosis the
      focal lesion is in one lung, whereas the apical lesion is limited to the opposite
      apex. This relation affords no support to the view that tuberculous lesions may
      be transmitted to the apex by way of the lymphatics.

PMID- 19868150
TI  - CICATRIZATION OF WOUNDS : IX. INFLUENCE ON THE HEALING OF WOUNDS OF VARIATIONS IN
      THE OSMOTIC TENSION OF THE DRESSING.
AB  - In the study of the action of non-antiseptic substances on the rate of
      cicatrization, the chief obstacle encountered is the facility with which wounds
      become reinfected under an aseptic dressing. At the beginning of Experiment 1 the
      wound was sterile. It was subjected to flushing with distilled water for 2 hours,
      then to flushing with 30 per cent sodium chloride solution for another 2 hours.
      During that time no special precaution was taken to sterilize the wound and the
      dressing was left intact until the following morning. It was then found that the
      wound contained from 30 to 50 bacteria per field. The following day, after the
      wound had been subjected to the same treatment, the number of bacteria had
      increased to 50 and 100 per field, and as an immediate consequence the surface of
      the wound increased from 12 to 12.6 sq. cm. in 2 days. The wound was then dressed
      antiseptically and was found to be sterile 3 days later. Reinfection again took
      place the following day in spite of antiseptic dressing with chloramine paste 4
      parts per 1,000, which was applied for 20 hours. In Experiment 2 similar results
      were observed. After 2 days of flushing with distilled water, the number of
      bacteria had increased to 50 per field. The wound was thereupon sterilized, but
      new reinfection ensued a few days later. Another wound on the same patient became
      reinfected under the same conditions after 1 day of sterile dressing. In none of
      the patients could the wounds be kept in a sterile condition throughout the whole
      experiment. It was impossible to maintain the sterility of a wound under aseptic
      dressing. Dakin's solution was therefore injected every 4 hours, or less often,
      according to the degree of infection, or chloramine paste was applied during the
      night. If there were 3 or 4 bacteria per field, the experiment was discontinued
      in order that the wound might be sterilized again. The cicatrization and
      bacteriological curves of Experiment 4 show that by the application of chloramine
      paste a wound may be maintained in an appropriately bacteriological condition for
      carrying out an experiment. Nevertheless, in spite of the antiseptic precautions
      taken, it was necessary to interrupt this experiment on two occasions, on
      December 13 to 15 and on December 18 to 22, in order that a complete
      sterilization of the wound might be effected. When the sterilization was
      performed as soon as the bacteria were discovered, little retardation occurred in
      the process of cicatrization. Moreover, the reinfection from the skin was often
      due to fine bacilli which have but mild retarding action on the rate of healing.
      The use of at least six flushings in 2 hours with Dakin's solution or of 12
      hours' dressing with chloramine paste 10 parts per 1,000, was necessary to keep
      the wound in a condition of surgical asepsis. The action of distilled water was
      studied in Experiments 1, 2, and 3. In Experiment 1 the wound was subjected to
      flushing with distilled water first for 2 hours, then 4 hours, and later for 8
      hours per day. The wound was maintained in a condition of mild infection. No
      marked modification, either acceleration or retardation, was noted in the rate of
      repair during the period that the treatment was applied. From November 21 to 25
      the wound was almost clean and the observed curve remained parallel to the
      calculated curve, showing that distilled water did not retard the rate of
      healing. In Experiment 2 the wound was subjected to uninterrupted flushing with
      distilled water, first for 2 and 8 hours, then for 24 hours. It was continued
      from November 24 to 30; viz., for 112 hours out of 120, without the occurrence of
      any marked modification of the course of healing. The bacteriological curve
      showed that from November 22 to 27 inclusive the wound was kept aseptic. The
      slight retardation which occurred afterwards was probably brought about by the
      infection. In Experiment 3 the wound was subjected to flushing with distilled
      water, first for 2, then for 4, 6, and 8 hours, a total of 20 hours in 4 days.
      From November 21 to 24 the wound remained surgically aseptic. No modification in
      the rate of healing occurred. The action of the hypertonic sodium chloride
      solution was studied in a similar way. In Experiment 4 the wound was flushed at
      first with 40 per cent sodium chloride solution, from December 4 to 9 for 12
      hours a day, and from December 10 to 13 for 24 hours a day, making a total of 144
      hours out of 240 hours. At the end of this time the surface area of the wound
      coincided exactly with the calculated area. Owing to reinfection the experiment
      was suspended. From December 24 to 29 the wound was kept in contact with 50 per
      cent sodium chloride solution for 54 hours, and after December 30 flushing with
      80 per cent solution for 24 hours a day was resorted to. The total amount of time
      involved in the above treatments was 174 hours with 40 per cent solution, 72
      hours with 50 per cent solution, and 120 hours with 80 per cent solution. On
      January 1, the surface measured 11 sq. cm. and the calculated surface was 11.3
      sq. cm. On January 5 the. surface observed was 10 sq. cm. and the calculated
      surface was 9 sq. cm. It should be noticed that on January 5 the bacteria
      numbered 4 per field, which might account for the difference. In Experiment 5 the
      wound was flushed for 24 hours every day with 50 per cent sodium chloride
      solution from December 11 to 18, a total of 192 hours. From December 18 to 24 the
      wound was dressed with agar-agar cakes containing 40 per cent sodium chloride.
      The concentration was raised to 50 per cent from December 24 to 27. The
      cicatrization curve indicates only a slight retardation of the repair which can
      be attributed to infection when both cicatrization and infection curves are
      compared. The temporary acceleration on the 13th may have been due to the
      influence of the dressing, but as it did not occur again an experimental error is
      probably the cause of the change observed in the curve. In Experiment 6 two
      practically identical wounds at a distance of but a few centimeters from each
      other were located on the right thigh of Patient 721. The areas of the wounds
      were respectively 40 and 33 sq. cm. One of the wounds was flushed with distilled
      water only. The other was subjected to the action of 40 per cent sodium chloride
      solution. From December 20 to 25 both wounds were in a condition of surgical
      asepsis. However, the cicatrization curves show that in spite of the difference
      of treatment the rate of healing was not modified. The rate of healing of the
      wounds did not therefore apparently undergo any measurable modification under the
      influence of distilled water or hypertonic salt solution. It is well known that
      the osmotic changes of the medium have a marked influence on tissues deprived of
      circulation. But it seems that a tissue with normal circulation is protected by
      it against the changes of the osmotic pressure occurring at its surface. The
      above experiments show that apparently the conditions of the tissues of a wound
      are not modified by the changes of the osmotic pressure of the dressing. The
      beneficial effects of hypertonic sodium chloride solution on the sterilization of
      wounds and on the rate of healing recently described by various surgeons are
      possibly an illusion due to lack of precise technique.

PMID- 19868151
TI  - HUMAN PULMONARY DISTOMIASIS CAUSED BY PARAGONIMUS WESTERMANNI.
AB  - 1. The morbidity of pulmonary distomiasis among the school children in the plains
      of the Prefecture of Shinchiku is 4.3 per cent, while in the mountainous regions
      among the savages it reaches in some districts 50 per cent. 2. Seventeen species
      of cercariae were discovered in fresh water mollusks in the Prefecture of
      Shinchiku, Formosa. But it was impossible to ascertain from morphological
      characteristics alone which of them developed into the pulmonary fluke.
      Consequently, the eggs of the pulmonary fluke after hatching into miracidia were
      allowed to come into contact with several species of fresh water mollusks, of
      which they infected two. But as it was difficult to keep the two spedes alive in
      the aquarium long enough to get cercariae, the second intermediate hosts of the
      pulmonary distomas were looked for in the severely infected villages of the
      savage tribes. 3. The miracidia of the pulmonary distomas leave the egg about 4
      weeks after they are first set free in the water, and if they do not reach
      mollusks they soon die. 4. Three species of fresh water mollusks were found to
      act as the first intermediate host of the pulmonary distomas; viz., Melania
      libertina Gould, Melania tuberculata Mueller, and Melania obliquegranosa Smith.
      5. The cercariae of the pulmonary distoma may be identified by their small size
      and a spine in the oral sucker. They develop in the liver of the three spedes of
      Melania mentioned above. 6. The second intermediate hosts of the pulmonary
      distoma,detected in the Prefecture of Shinchiku, are the following three species
      of fresh water crabs: Potamon (Geothelphusa) obtusipes Stimpson (native name, red
      crab), Potamon (Geothelphusa) dehaanii White (native name, dung crab), and
      Eriocheir japonicus De Haan (native name, hairy crab). In addition it was
      discovered that the following two species might act as intermediate hosts:
      Sesarma dehaanii Milne-Edwards and Potamon (Parathelphusa) sinensis Milne
      Edwards. In Formosa four of the five species are the carriers of the cercariae.
      7. The encysted cercariae are found in the gills, liver, and muscle, and have an
      elongated dark excretory vesicle in the middle of their bodies. They resemble the
      adult flukes. 8. Full grown encysted cercariae fed to dogs develop into mature
      pulmonary distomas and begin to lay eggs in about 90 days. 9. In the final host
      the parasites are taken into the alimentary canal as encysted cercariae. They
      liberate themselves from the cysts in the intestine and bore through the jejunum
      into the abdominal cavity. They then pierce the diaphragm, enter the thoracic
      cavity, and piercing the pleura reach the lungs. In the parenchyma of the lungs
      they form cysts and develop into adult forms. 10. The chief causes of pulmonary
      distomiasis are the eating of raw or insufficiently cooked crabs infected with
      the cercariae of Paragonimus westermanni, and the drinking of river water
      containing them.

PMID- 19868152
TI  - THE DISTRIBUTION IN THE HUMAN BODY OF SPIROCHAETA ICTEROHAEMORRHAGIAE.

PMID- 19868153
TI  - THE RAT AS A CARRIER OF SPIROCHAETA ICTEROHAEMORRHAGIAE, THE CAUSATIVE AGENT OF
      WEIL'S DISEASE (SPIROCHAETOSIS ICTEROHAEMORRHAGICA).
AB  - 1. On the basis of these findings, we conclude that the extermination of rats and
      field mice is a highly important prophylactic measure against Weil's disease. 2.
      The chemical composition of soil and water plays animportant part in the
      development of Spirochoeta icterohoemorrhagioe, and consequently in the spread of
      the disease of which it is the causative agent.

PMID- 19868154
TI  - THE CLINICAL ASPECTS OF SPIROCHAETOSIS ICTEROHAEMORRHAGICA OR WEIL'S DISEASE.

PMID- 19868155
TI  - A CONTRIBUTION TO THE ETIOLOGY AND PATHOLOGY OF RAT-BITE FEVER.
AB  - Of the two postmortem examinations on rat-bite fever previously reported, the
      patient of Miura and Toriyama, a woman, aged 32 years, died on the 70th day after
      the onset of the disease. Anatomically there were no marked changes. Histological
      examinations were not made. Macroscopically, the following findings are reported:
      increase of cerebrospinal fluid, hyperemia of the meninges, inflammatory edema of
      the lungs, cloudy swelling of the liver, etc. The other, Blake's case, was a
      woman of 67, who died 1 month after the bite of a rat. The anatomical findings
      were acute ulcerative endocarditis, subacute myocarditis, interstitial hepatitis,
      glomerular and interstitial nephritis. The suprarenals contained a large amount
      of perivascular fluid. There were infarcts in the spleen and kidney. In general,
      the organs were hyperemic; the lung showed hemorrhages and edema, Histologically,
      Blake found marked degeneration, necrosis, and infiltration in the cardiac
      muscles, infiltration of polynuclear cells, and increase in the interstices of
      the liver, also marked polynuclear infiltration of the shrunken kidney.

PMID- 19868156
TI  - CIRCULATING IMMUNITY PRINCIPLES IN RAT-BITE FEVER.
AB  - Summarizing the results that have been cited, we have proved that the blood serum
      of convalescents from rat-bite fever contains antibodies which are specific
      against the causative agent of that disease. The serum of rat-bite fever was
      capable of destroying the spirochetes not only in the hanging drop preparations,
      but also in the peritoneal cavity of guinea pigs. The guinea pigs employed for
      Pfeiffer's test always remained well. In the experimentally infected mice
      receiving intravenously or intraperitoneally serum equalling in quantity the
      amount of infected blood, the numbers of spirochetes were greatly decreased or
      they disappeared for a definite period. It is not yet clear how long after
      recovery from rat-bite fever the antibodies are effective in the blood of human
      beings, and further investigations are needed to elucidate this point. In our
      experiments we found that serum taken from Case I showed definite spirochetolytic
      and spirocheticidal properties 11 months after the onset of the disease. In Case
      2, the period was 6 months, and in Case 3, 3 months following the onset of rat
      bite fever.

PMID- 19868157
TI  - PULMONARY EMBOLISM : AN EXPERIMENTAL STUDY.
AB  - Emboli made of paraffin and the animal's own blood were sent into the venous
      circulation of dogs. Death did not occur until the pulmonary circulation was
      practically occluded. The results were the same whether the blood pressure of the
      animal was normal or depressed by ether or disease and whether the procedure was
      carried out under ether or local anesthesia.

PMID- 19868158
TI  - THE VISCOUS METAMORPHOSIS OF THE BLOOD PLATELETS.
AB  - From the experiments above described it is evident that the viscous metamorphosis
      of the blood platelets in shed blood is intimately associated with the early
      stages of coagulation and that the presence of calcium is a very important
      element, though perhaps not absolutely necessary. No constant differences in this
      phenomenon could be detected with platelets or coagulating elements from the
      blood of normal or diseased individuals or from man or rabbits. All the
      substances, with the exception of egg white, causing this phenomenon were derived
      from the blood either during the alteration of fibrinogen or after it had been
      acted on by thrombin. It seems that the substances or mixtures capable of
      producing the metamorphosis are especially those associated with the early stages
      of coagulation or capable in the test-tube of forming or liberating that active
      coagulating element known as thrombin. The substance in serum that is capable of
      metamorphosing platelets seems to be attached to the globulin fraction rather
      than the albumin fraction and is destroyed by heat at temperatures which destroy
      prothrombin, thrombin, and serozyme, and precipitate fibrinogen. The reaction is
      not caused by pure thrombin or a mixture of pure thrombin and calcium, though
      substances causing the metamorphosis are intimately related to thrombin. The
      metamorphosis seems to be caused by serozyme-like substances as shown both by the
      fact that barium sulfate absorbs the power of serum to cause the reaction and
      that a serozyme-like substance is probably to be recognized in all the substances
      or mixtures, including egg white, causing this change in the platelets, except
      perhaps when thrombin and fibrinogen are reacting. It is to be noted that in
      serozyme are contained antithrombin, calcium, and potential thrombin, and that a
      combination of these isolated factors mixed together occasionally allowed the
      viscous metamorphosis to occur and not infrequently an abortive metamorphosis.
      The pseudo- or abortive metamorphosis caused by the mixture of pure thrombin,
      antithrombin, and calcium may be interpreted on the supposition of a close
      approximation but not a real reproduction of the colloidal state known as
      serozyme. That such a reaction is related to real viscous metamorphosis is
      suggested, because it sometimes occurred with the above mixture and when thrombin
      and heavily oxalated plasmas were reacting, rather than a real metamorphosis.
      Simple agglutination of the platelets may occur independently of a viscous
      metamorphosis, though an agglutination of platelets is to be considered an
      integral part of the viscous metamorphosis phenomenon. The inconstant results
      seen with the cephalin-treated sera are probably due to the fact that exactly the
      same mixtures were not obtained. The results with cephalin-soaked and platelet
      soaked sera and with dilutions of sera suggest that the reaction of viscous
      metamorphosis of the platelets is quantitative.

PMID- 19868159
TI  - STUDIES ON BACTERIAL ANAPHYLAXIS AND INFECTION.
AB  - We have attempted in the preceding experiments the beginning of an analysis of
      bacterial anaphylaxis and its relation to the occurrences in the animal body
      during an infectious disease. We have shown that the sensitization of the tissues
      of guinea pigs, as indicated by the isolated uterus, required 3 to 5 days even
      when passive sensitization was employed, and that in these relations conditions
      with bacterial sensitization were entirely analogous to those revealed for serum
      anaphylaxis by Dale and Weil especially. It has become apparent that the
      sensitized uterus reacted not at all with whole bacteria or whole red cells, or,
      in other words, that before reaction with sensitized organs could occur an
      extraction or solution of the bacterial cell must take place. That bacteria yield
      some of their substance to the circulating blood during the course of infection
      was to be expected, but it has been definitely indicated, we think, by our
      complement fixations. The mechanism of injury in the sensitized animal or in the
      human being so far along in typhoid fever that antibodies have begun to develop
      is in part one in which antigen, derived from the bacilli and brought into
      solution, or rather suspension, in the blood stream, reacts with antibodies which
      are from the beginning, or have subsequently become, integral parts of the cell
      protoplasm, the entire process taking place within the cell. This last point is
      indicated by the failure to sensitize by simply soaking the normal uterus in
      antiserum. This, however, cannot be the entire story of injury. We know that
      typhoid antigen injected into normal animals in moderate amounts will render them
      gradually sick and eventually kill them. Also, a sufficient amount injected into
      a normal animal will occasionally produce acute symptoms, in every respect
      similar to the reaction produced in sensitized animals by smaller doses. We have
      shown that such acute symptoms in normal animals were not due in any degree to
      tissue sensitiveness, since even very large quantities of antigen will produce no
      response on the part of the normal uterus. It is reasonable to suppose,
      therefore, that the injury, gradual or acute, in the normal animal, is in no
      respect referable to tissue sensitiveness to the whole antigen, but rather must
      be referred to some series of phenomena which occur in the circulation. The acute
      shock of normal animals may possibly, therefore, be entirely due to an
      intravascular reaction. Whether this is one of antigen-splitting, or of
      antienzyme removal in the sense of Jobling is a point on which these experiments
      throw no light. It is true that we have never succeeded in producing acute toxic
      symptoms either in the whole animal or in the isolated uterus with serum from
      animals acutely ill. This we eliminate as negative evidence inasmuch as we
      believe that the toxic substances need at no given time be present in the blood
      stream in sufficient concentration to render such an experiment successful. They
      are probably absorbed and do their injury almost as rapidly as formed, an
      assumption which is based on the speed with which symptoms develop. It is
      possible, and not to be denied on the basis of any experiment that we can devise
      at present, that the gradual illness of the normal animal and the occasional
      acute shock of these animals may be based on entirely different mechanisms. In
      both cases, however, in normal animals, they seem to be intravascular. And since
      the symptoms of acute shock which can be produced in sensitized animals with
      moderate doses can also, though only occasionally, be produced in normal animals
      with larger doses, it is reasonable to suppose that the poisons produced
      intracellularly in the one may be similar to those produced intravascularly in
      the other. It does not seem likely that the specific circulating antibodies are
      in any way sources of increased injury to an animal spontaneously infected with
      bacteria. If sufficiently powerful at the beginning they may even prevent tissue
      injury, first by increasing phagocytosis, then by producing intravascular
      agglutination, and finally, as indicated by our experiments, even by removing a
      part of the antigen from possible reaction with the cell, though in this last
      respect our experiments indicate that they functionate imperfectly. It is more
      probable that their chief protective action to the sensitized body lies in
      removing the whole bacteria from the possibility of intravascular disintegration,
      which, as we have shown, is prerequisite to anaphylactic injury of the tissues of
      the host. We would tentatively summarize our opinion as to the occurrences in the
      typhoid-infected body as follows: Early injury is probably due to disintegration
      of part of the bacteria in the course of which albumose-like bodies are
      liberated, and, following which, intravascular reactions result in the formation
      of toxic substances, perhaps by some form of proteolysis. Since the accumulation
      of bacteria during these stages is relatively slight, this form of injury
      probably plays little part in producing symptoms. Indeed, the experiment by which
      acute injury is produced in the normal guinea pig by the sudden injection of
      several times the lethal dose of partly dissolved bacteria, finds no analogy in
      the spontaneously diseased body. At this time the tissues are not sensitive, but
      as antigen absorption progresses and the tissues are stimulated to react,
      sensitiveness develops, which renders them much more delicately amenable to
      injury by direct reaction with even small amounts of dissolved but otherwise
      unaltered antigen. This process is directly counteracted by circulating
      antibodies which tend to remove the bacteria from the possibility of yielding
      their antigen to solution by agglutinating them, aiding phagocytosis, and to a
      slight extent even neutralizing dissolved antigen. It seems likely, therefore,
      that the symptoms which appear as the incubation time ends are largely those due
      to cellular sensitization which probably begins before any considerable amount of
      circulatory antibodies is present. The circulating antibodies would seem to have
      little or nothing to do with intravascular injury, the ferments responsible for
      this, however much it may occur, probably consisting of the non-specific
      proteases studied in this connection by Jobling. Finally it appears that highly
      sensitized animals are more easily killed by typhoid antigen than are normal
      animals, provided they do not dispose over unusually large amounts of circulating
      antibodies. Cure would consist of a gradual checking of growth and final
      destruction of the bacteria, and the consequent cessation of antigen liberation,
      but delicate hypersusceptibility would probably persist for some time after cure
      and immunity have been established. Just what the relation between tissue
      hypersusceptibility and immunity is remains a problem for further study.

PMID- 19868160
TI  - INCREASED VIRULENCE OF THE HOG-CHOLERA BACILLUS PRODUCED BY PASSAGE THROUGH
      RABBITS.
AB  - By passage through a series of eleven rabbits a culture of the hogcholera
      bacillus has increased its virulence a thousand times. A subcutaneous injection
      of twenty organisms, or 0.00000001 cc. of a 24 hour bouillon culture, or a drop
      of a bouillon culture rubbed lightly into the shaven skin, produces, in the
      rabbit, a characteristic disease resulting in death on or about the 6th day.

PMID- 19868161
TI  - THE SIGNIFICANCE OF AGGLUTININS IN THE IMMUNITY OF THE RABBIT TO THE HOG-CHOLERA
      BACILLUS.
AB  - Rabbits may show a high agglutination titer to the hog-cholera bacillus and have
      no immunity and on the other hand immune animals may have a comparatively low
      agglutination titer. In other words, with this organism the height of the
      agglutination titer does not indicate the degree of immunity. As this bacillus so
      closely resembles the typhoid bacillus biologically and pathologically, it seems
      safe to conclude, until evidence is brought forth to the contrary, that in man
      the height of the agglutination titer does not indicate the actual degree of
      immunity to the latter organism. The same would apply to other members of the
      typhoid-colon group. It would not be wise to draw a more general conclusion until
      other organisms have been tested. This does not mean that agglutinins are not
      related to immunity but it brings up the question of the wisdom of using them as
      a guide in immunization with the colon-typhoid group. When injected into the
      normal, vaccinated, or immune rabbit, the virulent hog-cholera bacillus is
      rapidly clumped and disappears from the circulation. 40 minutes after injection
      these organisms can be found in phagocytes in the liver. The fact that the normal
      rabbit gives this intra vitam agglutination is an exception to the findings of
      Bull that virulent organisms remain in the circulation for some time after
      injection.

PMID- 19868162
TI  - THE NEUTRALIZATION OF ANTIPNEUMOCOCCUS IMMUNE BODIES BY INFECTED EXUDATES AND
      SERA.
AB  - 1. In empyema fluids resulting from infection with pneumococci there are present
      large amounts of soluble substances which have the property of neutralizing
      pneumococcus antibodies. 2. Similar substances are found in the blood of infected
      rabbits. 3. When immune serum is injected into infected rabbits the immune
      substances disappear very quickly, and therefore are prevented from activity in
      overcoming the infection. 4. When immune serum is administered to patients
      severely infected with pneumococci, the immune bodies may also disappear very
      rapidly, and this disappearance is probably associated with the presence of such
      soluble substances in the blood. 5. The serum only becomes effective when these
      substances are neutralized. 6. The study of agglutination curves is of value in
      showing why in certain instances favorable results have not followed the use of
      immune serum. 7. It is important that in severely injected patients the serum be
      administered early in the disease and that the initial dosage be large.

PMID- 19868163
TI  - THE ELABORATION OF SPECIFIC SOLUBLE SUBSTANCE BY PNEUMOCOCCUS DURING GROWTH.
AB  - 1. A specifically reacting substance of bacterial origin is present in the cell
      free fluids of young cultures of pneumococcus. This substance is present when the
      organisms are growing at their maximum rate and undergoing little or no cell
      death, and consequently its. presence is not dependent upon cell disintegration
      but represents the extrusion of bacterial substance by the living organism. 2.
      The blood and urine of rabbits experimentally infected with pneumococcus contain
      a similar specific soluble substance during the early hours of the infectious
      process. 3. Human beings suffering from lobar pneumonia have in their blood and
      more frequently in their urine a specific soluble substance of pneumococcus
      origin. The amount of this substance present in the urine varies in different
      individuals and the presence of a large amount is of unfavorable prognostic
      import. This specific precipitin reaction in the urine is of diagnostic value. 4.
      Rabbits injected with soluble pneumococcus material continue to excrete this
      substance for a considerable period of time. 5. The specifically soluble
      substance obtained from bacterial cultures and from the urine during infection is
      not destroyed by boiling, by precipitation with alcohol, acetone, or ether, or by
      trypsin digestion. 6. Studies are in progress at this time on the degree of
      toxicity and on the antigenic properties of the substance.

PMID- 19868164
TI  - ACIDOSIS AND ACID EXCRETION IN PNEUMONIA.
AB  - There is excreted in the urine of subjects ill with acute lobar pneumonia a large
      amount of organic acid which is free at a hydrogen ion concentration of 5.0.
      Acidosis as determined by the combined carbon dioxide in the plasma is seldom, if
      ever, severe.

PMID- 19868165
TI  - FURTHER STUDIES ON THE EPIDEMIOLOGY OF LOBAR PNEUMONIA.
AB  - 1. Pneumococci of Type I and Type II are responsible for the majority of the
      cases of lobar pneumonia. 2. Among the pneumococci found in the mouths of healthy
      individuals Type IV predominates, Type III is frequent, and atypical organisms of
      Type II are occasionally found. 3. Healthy persons intimately associated with
      cases of lobar pneumonia may harbor in their mouth secretions the highly
      parasitic pneumococcus of Types I and II. 4. Occasionally a carrier of Type I or
      Type II pneumococcus is encountered in whom it is impossible to trace any contact
      with an infected patient. 5. From the dust of homes where cases of pneumonia due
      to Types I and II have occurred, pneumococci of the same type may be recovered.

PMID- 19868166
TI  - THE PRODUCTION OF ANTIPNEUMOCOCCIC SERUM.
AB  - In the production of immune serum for therapeutic purposes strict attention must
      be paid to the immunological specificity of the bacteria used for immunization.
      At present the only serum of which the therapeutic value has been proven is that
      effective against Type I pneumococcus infection. This serum should have
      agglutinating power for Type I pneumococcus and should have the power of
      protecting mice against large amounts of virulent culture. Experiments have shown
      that for producing the primary immunity most rapidly several series of small
      doses of dead cultures should be given, the injections being made daily for 6 to
      7 days, followed by a week in which no injections are made. To produce the
      highest type of immunity probably living organisms are required. These should be
      given in moderate doses daily for 3 days, with an interval of a week between each
      series of injections. By following accurately the methods described, horses may
      be made to produce rapidly a high grade of specific serum. The observations so
      far made indicate the importance of employing small doses of culture frequently
      repeated in this form of immunization.

PMID- 19868167
TI  - STUDIES ON ANTIBLASTIC IMMUNITY.
AB  - Antipneumococcus serum under certain conditions apparently inhibits or retards
      the metabolic activities of the homologous pneumococcus. Antipneumococcus serum
      exhausted of its agglutinin content possesses no inhibitory properties. The
      degree of inhibitory action of antipneumococcus serum parallels its agglutinating
      power. No evidence has been found to indicate that the inhibition of the
      metabolic activities of the pneumococcus by antipneumococcus serum is due to a
      specific antienzymotic property of the serum. The evidence which has been
      obtained indicates that the apparent inhibition of metabolic activity that occurs
      under certain conditions is due to agglutination of the pneumococci by the
      antipneumococcus serum and their consequent inability to grow in intimate contact
      with the whole medium. Antistaphylococcus serum inhibits the liquefaction of
      gelatin and the formation of pigment by Staphylococcus pyogenes aureus. Further
      experimentation is necessary to determine the mechanism of this inhibitory
      action. Antistaphylococcus serum does not inhibit those metabolic activities of
      Staphylococcus pyogenes aureus essential to the growth and multiplication of the
      organisms.

PMID- 19868168
TI  - FURTHER STUDIES IN EXPERIMENTAL ATHEROSCLEROSIS.
AB  - Cholesterol dissolved in sesame oil and injected regularly for a period of from 7
      to 8 months into the jugular vein of four young dogs has caused in each animal
      larger and smaller nodules protruding to some degree into the lumen of the
      pulmonary artery and also here and there some diffuse thickenings, the whole
      closely resembling human arteriosclerosis. These changes commence at the origin
      of the pulmonary artery immediately behind the semilunar valves. They seem a
      little more pronounced in those dogs that had the aorta tied. Microscopically the
      lesions are seen to be primary in the media. They consist of a more or less
      violent disorganization of the elastic elements and displacement of the muscular
      tissue. As a consequence wide gaps, apparently filled with plasma, are formed in
      the media. The entire process is localized principally in the inner third of the
      media. There is no evidence of fatty degeneration either in the elastic elements
      or the muscle. Typical sclerotic hyperplasia of the intima is found over some of
      the prominent median nodulations while over others the intima is normal.
      Hyperplastic sclerosis of the intima is also found in places where the media is
      intact or only slightly damaged. Some of the larger branches of the pulmonary
      artery well within the lung tissue are somewhat dilated and show extensive
      hyperplasia of the intima over almost normal media. Peculiar small nodules are
      seen in the media of the two main branches of the pulmonary artery which are
      found to consist of frank hyperplasia of the elastic and muscular elements
      arranged in more or less regular concentric circles. The capillaries and smaller
      and smallest arteries within the lungs are not affected. Cholesterol in
      phagocytes and in droplets between the tissue elements is present in very small
      quantities and does not take any active part in the process. The entire process
      represents in all probability an early stage of arteriosclerosis, a result of
      purely mechanical stress brought about by the very extensive but more or less
      intermittent blocking of the pulmonary circulation by the oil. The musculature of
      the artery appears to be the main force applied to overcome the resistance in the
      circulation. In no case has hypertrophy of the right heart been found. The
      lesions in the pulmonary arteries of the dogs produced experimentally are closely
      analogous to atherosclerosis of the human pulmonary artery.

PMID- 19868169
TI  - THE PROPHYLACTIC AND THERAPEUTIC PROPERTIES OF THE ANTITOXIN FOR BACILLUS
      WELCHII.
AB  - 1. It has been possible to confer on guinea pigs a passive immunity of about 2
      weeks' duration to Bacillus welchii toxin through a protective administration of
      the antitoxin. 2. Guinea pigs which bad received a prophylactic dose of Bacillus
      welchii antitoxin exhibited pronounced resistance to infection with the virulent
      bacilli for a period of 12 days. 3. Established infections in guinea pigs with
      Bacillus welchii have been arrested and controlled by treatment with the
      antitoxin. 4. The opinion has been expressed that it will be possible to prevent
      Bacillus welchii infection in man through the prophylactic use of the antitoxin
      and developed cases of the infection may be controlled by therapeutic injections
      of the same agent.

PMID- 19868170
TI  - THE RELATION OF THE SPINAL CORD TO THE SPONTANEOUS LIBERATION OF EPINEPHRIN FROM
      THE ADRENALS.
AB  - 1. After section of the spinal cord in cats in the cervical region, as low as the
      last cervical segment, epinephrin continues to be liberated from the adrenal
      glands. This liberation has all the characters of the normal secretion with
      intact central nervous system. It is sustained through the same nerve paths
      connecting the cord with the adrenals. 2. After section of the cord in the
      middorsal region the spontaneous liberation of epinephrin from the adrenals is
      abolished within the limits of detectability by the methods employed (denervated
      eye reactions of Meltzer, and rabbit intestine and uterus segments). 3. The
      portion of the cord concerned in the liberation of epinephrin does not appear to
      extend much below the third thoracic segment. 4. In acute experiments on cats
      under urethane anesthesia no change in the rate of liberation of epinephrin,
      which could be detected by the tests employed, was observed when the cord was
      severed in the cervical region.

PMID- 19868171
TI  - EFFECT OF STIMULATION OF SENSORY NERVES UPON THE RATE OF LIBERATION OF EPINEPHRIN
      FROM THE ADRENALS.
AB  - An attempt was made to determine whether stimulation of afferent nerves (sciatic
      and brachial) produced a detectable increase in the rate of liberation of
      epinephrin from the adrenals, as determined by testing adrenal vein blood on
      rabbit intestine and uterus segments. The result was negative.

PMID- 19868172
TI  - BACTERICIDAL FLUORESCENCE EXCITED BY X-RAYS.
AB  - X-ray fluorescence has been pointed out as a mechanism offering exceptional
      possibilities in the development of physicochemical therapy. Experiments are
      given which demonstrate that under these conditions the x-rays may have a strong
      bactericidal effect. The x-rays alone have a partial bactericidal action on water
      suspensions of typhoid bacilli.

PMID- 19868173
TI  - HEMOLYSINS OF VEGETABLE ORIGIN.
AB  - 1. The sap of Cotyledon scheideckeri possesses hemolysins for the red corpuscles
      of different animals. 2. The hemolysins of vegetable sap can be bound by
      erythrocytes and cannot be separated. 3. A definite quantity of erythrocytes is
      able to extract from the sap only a part of the hemolysins it contains. 4. The
      quantity of hemolysins in the sap of different plants is subjected to the same
      fluctuations as that of bacterial agglutinins, precipitins, and hemagglutinins.
      5. As the hemolysins are bound by erythrocytes, the hemolysis can take place not
      only at 37 degrees but also at 15-16 degrees . 6. The thermostability of the
      hemolysins varies from one individual plant to another. 7. In many cases the
      vegetable sap loses its hemolytic properties at a certain temperature and
      recovers them at a higher one. 8. The vegetable sap is unable to produce complete
      hemolysis of erythrocytes. 9. But the sap of many plants acquires the power to
      dissolve red corpuscles completely after I hour of heating at 134 degrees and 144
      degrees . 10. Erythrocytes modified by Cotyledon sap cannot be dissolved
      completely even by distilled water. 11. The agglutination of the erythrocytes and
      their hemolysis are conditioned, probably, by different substances. 12. The
      hemolytic amboceptor and the hemolysin of Cotyledon scheideckeri can be bound
      with the same receptor of the erythrocytes.

PMID- 19868174
TI  - STUDIES ON THE DEVELOPMENT OF TOXICITY IN INTESTINAL SECRETION.
AB  - 1. Intestinal secretion, collected by the method described in this paper, is non
      toxic when fresh. 2. This secretion, when heated immediately to 90-95 degrees C.
      and kept sterile, remains non-toxic. 3. This secretion, when not heated, remains
      non-toxic when kept under chloroform and toluene, even if incubated at 37 degrees
      C. 4. This secretion, when not heated, but collected in a sterile flask, becomes
      toxic upon incubating 18 hours, producing symptoms like those of closed loop
      fluid. 5. The secretion, when treated with chloroform and toluene, and later
      incubated for 18 hours, after these preservatives have been removed by
      distillation at 60 degrees C., does not produce lesions typical of closed loop
      fluid.

PMID- 19868175
TI  - A COMPARATIVE STUDY OF SERUM AND LYMPH FERMENTS AFTER FEEDING.
AB  - In these experiments in which the lymph and serum ferments and antiferment have
      been studied separately, the changes that are found to occur are uniform and
      consistent. Possibly as a result of increased blood flow through the ferment
      producing organs a moderate amount of protease is directly absorbed into the
      blood stream, but when intestinal digestion is actively under way this rapidly
      diminishes in extent. If any protease is absorbed during digestion from the
      gastrointestinal tract it is probably removed when it reaches the liver. The
      ereptase, or peptidase, is evidently absorbed directly from the intestinal tract
      and enters the circulation through the lymphatic channels. The influence of the
      diet on the antiferment of the lymph is striking and accounts for the
      fluctuations observed in previous experiments. Following the milk meal the
      increase occurs gradually in the lymph in an amount that, when diluted in the
      blood stream, would be only nominal. When the fats of the milk were replaced by
      olive oil in large amounts it is surprising to find a decrease in the antiferment
      instead of an increase in titer, as might be expected in view of the nature of
      the antiferment. This result, however, is probably due to the fact that the
      antiferment lipoids of the serum and lymph may exist in both water and fat
      dispersion phases, but are active as antiferments only when in the former. If the
      amount of the fats of the serum is increased, as it is after the olive oil
      feeding, more of the antiferment will enter the fat phase and will as a result be
      rendered inactive. When the feeding included the sodium oleate, the anti-ferment
      was in consequence increased in both the serum and the lymph, some of the soap
      being apparently absorbed directly into the blood stream. It is possible that the
      titer of the antiferment may be altered, therefore, by means of selective
      feeding.

PMID- 19868176
TI  - A COMPARATIVE STUDY OF LYMPH AND SERUM FERMENTS DURING PROTEIN SHOCK REACTIONS.
AB  - The relation of two phenomena involved in the mechanism of recovery following
      protein shock therapy is shown in these experiments to be due to changes that
      concern the lymph rather than the serum. The first of these, the increase in the
      rate of flow of the lymph, has been suggested by Teague and McWilliams as a
      possible factor in recovery from infection when due to bacteria proliferating in
      the lymph spaces and inaccessible to the antibodies of the serum (typhoid). By
      means of the protein shock, antibody-rich fluids (serum) are forced into the
      lymph channels. That the antibodies of the serum are augmented following the
      shock has been demonstrated by Culver (4). With this possibility in mind it is to
      be expected that bacterial infection not confined to the lymph spaces will not be
      influenced by shock therapy to the same extent. How far this holds true we are
      unable to state, although von Decastello (5) has called attention to the fact
      that while he was able to cause rapid lysis or a crisis in typhoid patients
      following the shock reaction, the injection of a similar amount of vaccine in
      typhus fever was without effect. The second factor, the great increase in the
      antiferment, is clearly due to the amount of the antiferment entering the general
      circulation through the lymph stream. This accounts for the marked fluctuations
      observed in the titer of the serum antiferment in patients following protein
      shock. If, for instance, the original titer of the lymph is less than that of the
      blood, the first flushing of the lymphatic current into the blood channel will
      tend to lower the titer of the serum, but with the increased amount in the lymph
      after the shock the titer of the serum will also increase. Bacteria proliferate
      best where the antiferment is absent, as Wright (6) has noted in his studies on
      war wounds, a fact that is also commonly applied in bacteriological technique
      when we employ ascitic fluids, containing relatively little antiferment,
      preferably to serum, in culture media. The increased lymph flow that follows the
      shock reaction would have value then, not only in forcing specific antibodies
      into the lymph channels, but 'in increasing the antiferment there as well, which
      would aid in checking the growth of bacteria.

PMID- 19868177
TI  - STUDIES IN GLOMERULONEPHRITIS : III. AN ATTEMPT TO PRODUCE GLOMERULONEPHRITIS BY
      REPEATED INJECTIONS OF BACTERIA.
AB  - Repeated injections into the blood stream of streptococci and stapnylococci
      derived from cases of scarlet fever, and of Bacillus coli communior failed to
      produce typical glomerulonephritis even when immune antibodies could be
      demonstrated in the serum in high dilutions. Bacteriolysis of streptococci was
      not found by the usual tests in intro or by the Pfeiffer procedure. It is
      therefore concluded that the weight of evidence is against the theory that
      glomerulonephritis is due to immune bacteriolysis of streptococci. The
      experiments also failed to give any support to the hypothesis of allergy or. of
      sensitization as a factor in the production of the disease. Evidence is presented
      to show that bacterial emboli are rapidly removed from the glomerular capillaries
      by leukocytes, and that this embolism, even after injections of enormous
      quantities of bacteria, affects but a small proportion of the glomeruli. It is
      again suggested that a circulating poison in the soluble state is responsible
      directly for the disease in question.

PMID- 19868178
TI  - THE INTERRELATION OF THE SURVIVING HEART AND PANCREAS OF THE DOG IN SUGAR
      METABOLISM : SECOND PAPER.
AB  - When the pancreas of a dog is perfused aseptically with a Locke's solution
      containing dextrose in physiological concentrations, the optical rotation of the
      perfusate is diminished, but its reducing power is unaltered. This change also
      occurs if dextrose is added to a sugarfree pancreatic perfusate and the mixture
      incubated. These perfusates yield osazones with lower melting points than
      glucosazone, but when the perfusates are hydrolyzed with weak acid their optical,
      rotations and the melting points of their osazones are increased. These changes
      do not occur with levulose, or with an extract of the pancreas and dextrose. When
      the heart, spleen, or kidneys are perfused with dextrose solutions hydrolysis of
      the perfusates does not increase their optical rotation or power of reduction.
      When a pancreatic perfusate containing dextrose is circulated through a living
      heart not only do the above changes take place but, in addition, the reducing
      properties of the perfusate are altered. Hydrolysis of such a perfusate increases
      its reducing power, its optical rotation, and the melting point of its osazone. A
      heart does not cause this effect either alone or when perfused together with the
      spleen or kidneys. Levulose perfused through the heart and pancreas is unchanged.
      These phenomena are believed to be due to an enzyme or enzymes obtained from the
      perfused pancreas. The changes in optical rotation, in reduction, and in the
      osazones are accounted for by different degrees of dextrose condensation. While
      the living heart can destroy both dextrose and levulose to some extent, the
      experimental results suggest that the enzyme or enzymes derived from the perfused
      pancreas have a specific action on dextrose and are responsible for certain
      essential steps by which dextrose is prepared for normal utilization.

PMID- 19868179
TI  - CARRIAGE OF THE VIRUS OF POLIOMYELITIS, WITH SUBSEQUENT DEVELOPMENT OF THE
      INFECTION.
AB  - A family group containing four children of whom all showed in varying degree
      symptoms of poliomyelitis is described. The source of infection and periods of
      incubation have been followed. Two of the children were proven by inoculation
      tests to carry the virus of poliomyelitis in the nasopharynx. Of these, one was
      detected to be a carrier after recovering from a non-paralytic attack of the
      disease, and the other was discovered to be a carrier about 5 days before the
      initial symptoms, attended later by paralysis, appeared. The original case from
      which the three others took origin was fatal; the youngest child, after quite a
      severe onset, was treated with immune serum, and made a prompt and almost perfect
      recovery. The nasopharyngeal secretions of two of the cases, taken 1 month after
      the attack, proved incapable of neutralizing an active poliomyelitic virus. The
      proposition is presented that every case of poliomyelitis develops from a carrier
      of the microbic cause, or virus, of poliomyelitis.

PMID- 19868180
TI  - A NOTE ON PETROFF'S CULTURAL METHOD FOR THE ISOLATION OF TUBERCLE BACILLI FROM
      SPUTUM AND ITS APPLICATION TO THE EXAMINATION OF MILK.
AB  - 1. Tubercle bacilli were isolated by the Petroff method from 64.8 per cent of the
      sputa which were found to be positive by the direct microscopic method. 2. The
      organism was recovered from 69.2 per cent of the samples of milk that were
      artificially infected. 3. Of the milk obtained through the New Haven Health
      Department Laboratory 8.4 per cent of the samples were found to contain tubercle
      bacilli, while none of the twenty-nine samples from the State Laboratory gave
      positive cultures. 4. All the guinea pigs (thirteen), except one, which were used
      as control animals died without any visible signs of tuberculosis. 5. Petroff's
      method for the isolation of tubercle bacilli from sputum may be applied
      successfully to the examination of milk. With slight modifications, the method
      should prove constant and reliable. The need of such a method for the examination
      of milk and milk products is apparent.

PMID- 19868181
TI  - THE BIOLOGICAL IDENTITY OF THE FRIEDLANDER BACILLUS.
AB  - We conclude therefore that this series of eleven lactose-negative organisms of
      the Friedlander type, grouped together by Perkins on the basis of fermentation
      reactions represents a single biological group. It can be distinguished from
      Bacillus aerogenes and other similar bacilli by cultural, fermentative, and
      serological reactions. There appears to be a close analogy between this group and
      Pneumococcus mucosus in the possession of a fixed cultural type, and the behavior
      toward immune serum. Both represent apparently a single biological group.
      Unfortunately no immune sera have been developed against the two strains that
      grew in moist and dry phases; it is possible that with immune sera for these
      light could be thrown on the relation suggested by Fitzgerald that the capsulated
      bacilli represent a parasitic development of the Bacillus coli group.

PMID- 19868182
TI  - THE EFFECT OF ALCOHOL ON THE REPRODUCTIVE TISSUES.
AB  - Administration of alcohol in the food of male white rats for 2 or more months, in
      daily quantities of 0.25 to 2.25 cc., results almost constantly in the appearance
      of marked degenerative alterations in the testicles. These changes affect the
      steps of spermatogenesis in inverse order to their occurrence, so that for some
      time before sterility and complete aspermia result, the animal is producing
      spermatozoa with all possible degrees of abnormality and deficiency. The possible
      relation of this abnormal spermatogenesis to the production of defective
      offspring is obvious. Individual rats show marked differences in the degree of
      change produced by equal amounts of alcohol. The fibrous, interstitial, and
      vascular elements of the testicle are not affected, except for intertubular edema
      compensating for tubular atrophy. These experimental observations harmonize with
      the necropsy findings in human alcoholics. No other tissue was found to be
      noticeably affected by the alcohol; especially to be remarked is the absence of
      cirrhosis or fatty infiltration in the liver.

PMID- 19868183
TI  - MENINGITIS IN AN INFANT DUE TO A HITHERTO UNDESCRIBED ORGANISM, MICROCOCCUS
      FLORENS.
AB  - These virulence tests lead us to believe that Micrococcus florens is pathogenic
      for mice, rabbits, and monkeys (Macacus rhesus), producing septicemia, and that
      it will also cause purulent meningitis in the two latter animals. The combined
      results of the biological reactions and of the agglutination tests lead us to
      believe that we are dealing with an organism which, though morphologically
      similar to the meningococcus, yet is entirely distinct. A review of the
      literature fails to reveal any description of a Gramnegative micrococcus which
      grows luxuriantly on all media tested, forms no pigment, and ferments arabinose,
      dextrose, and galactose.

PMID- 19868184
TI  - THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC
      JAUNDICE : XVI. THE INFLUENCE OF SPLENECTOMY AND OF BLOOD DISINTEGRATION UPON THE
      PRODUCTION OF BILE PIGMENT.
AB  - 1. In four animals with a bile duct-ureter anastomosis and without disturbance
      due to obstruction or absorption, the total quantity of bile pigment output
      during a day under normal conditions varied from 0.0618 to 0.0678 gm. These
      figures are practically identical with those of Stadelmann (9, 10) but lower than
      those given by Hooper and Whipple (7), who find that the average bile pigment
      excretion amounts to about 1 mg. per pound of body weight per 6 hours. 2. In all
      the experiments there is definite evidence of a decrease in bile pigment
      elimination after splenectomy. This is true not only of the elimination when no
      hemolytic agent is administered but also when excessive blood destruction is
      caused. Under the latter circumstances the amount of bile pigment is greatly
      increased but never reaches the high level of blood destruction before
      splenectomy. 3. These observations appear to show conclusively that the absence
      of the spleen influences the formation of bile pigment. To what extent the
      influence is mechanical, i.e., change in the course of the blood to the liver,
      and to what extent due to anemia, cannot be stated at present.

PMID- 19868185
TI  - STAGGERS IN SHEEP IN PATAGONIA.
AB  - After observations and experimental work both in the field and laboratory, the
      following conclusions seem justified. 1. Staggers is a non-infectious disorder
      affecting horses, cattle, and sheep. 2. The disease is characterized by weakness,
      muscular twitching, irregular movements of the head, stiffness of the limbs, and
      transient motor paralysis, accompanied with spastic spasms on excitement. There
      is also a derangement of vision and conjunctivitis. 3. The postmortem lesions are
      not characteristic. 4. We readily produced the disease by feeding susceptible
      sheep on a coarse tuft grass commonly known as coiron or pampa grass (Poa
      argentina). 5. The time required to produce definite symptoms by feeding the
      grass varied. Two animals developed typical staggers after two feedings; in
      another instance a period of 21 days of feeding was required. The average time
      for the production of unmistakable symptoms in our experiments was 10 days. 6.
      Many sheep recover from staggers spontaneously. A complete change of diet will
      usually effect a cure within 2 weeks. 7. Older .animals that have pastured for
      long periods on lands where the grass grows become tolerant and are rarely
      affected with staggers. 8. The grass is toxic to sheep at all seasons of the
      year. We fed late winter and early spring grass and grass in flower, and produced
      staggers in every instance. The young green grass is as toxic as any edible
      portion of the plant.

PMID- 19868186
TI  - THE DIVERSION OF THE PANCREATIC JUICE FROM THE DUODENUM INTO THE STOMACH. ITS
      EFFECTS UPON THE LEVEL OF GASTRIC ACIDITY AND UPON THE PANCREAS.
AB  - The mechanism described for maintaining the optimum level of gastric acidity is
      designated by Boldyreff as the "self regulation of the acidity of the contents of
      the stomach." In support of Boldyreff's hypothesis is the evidence obtained from
      many experiments carried out both on man and on animals, in which solutions of
      alkali and acid have been placed in the stomach. The introduction of acid fluid
      has led to a regurgitation of alkaline duodenal contents, whereas the
      introduction of alkaline solutions has called forth a secretion of acid gastric
      juice. The experiments reported in this paper were carried out for the purpose of
      ascertaining how the stomach would react, in as far as the secretion of
      hydrochloric acid is concerned, to a more or less continuous influx of relatively
      strong alkaline fluid, prolonged throughout the cycle of digestion. Numerous
      studies have shown that any serious interference with the process of
      regurgitation leads to a rise in the acidity level of the stomach; i.e., to a
      state of hyperacidity. There is but little evidence, however, to indicate whether
      the acidity level will be depressed temporarily or permanently (hypoacidity) when
      alkaline material, in considerable amounts, continues to enter the stomach. The
      influx of alkaline fluid was provided for by transplanting the larger pancreatic
      duct into the wall of the stomach after ligating and dividing the lesser duct.
      Specimens of test meal for analysis were withdrawn through gastric fistulas made
      after the method of Janeway. Animals prepared in this manner served also to
      furnish additional information regarding the possible relation of the
      hydrochloric acid of the gastric juice to certain acute inflammatory and chronic
      sclerotic changes in the pancreas. From the results of these experiments it
      appears that the presence of a considerable amount of pancreatic juice in the
      stomach throughout the period of digestion leads only to a moderate decrease in
      the acidity level of the ingesta in the later stages of digestion. Earlier in the
      process there is no constant alteration of the acidity level in either direction.
      The findings then serve not only to corroborate the views of Boldyreff, but also
      to demonstrate the remarkable compensatory activity of the gastric glands under
      conditions which entail an unusual quantity of alkali in the stomach. In addition
      the work has shown that when the larger pancreatic duct is properly transplanted
      into the wall of the stomach, it may remain patent for months. In animals in
      which this operative procedure has been carried out, the pancreas has been found
      to undergo no inflammatory or other degenerative changes. This finding is
      regarded as evidence against the postulation of Hlava that gastric juice is
      probably responsible for the occurrence of certain cases of acute hemorrhagic
      pancreatitis.

PMID- 19868187
TI  - THE ABIOTIC ACTION OF ULTRA-VIOLET LIGHT.
AB  - Typhoid bacilli are about one two-hundredth as sensitive to ultraviolet light of
      wave-lengths 2100 to 2800 Angstrom units as is the photographic plate. This
      sensitivity then falls off, decreasing rapidly to almost zero sensitivity at
      about 2970, the beginning of the sun's spectrum.

PMID- 19868188
TI  - CHANGES IN THE PERIPHERAL BLOOD CONSEQUENT UPON THE DIVERSION OF THE SPLENIC
      BLOOD INTO THE GENERAL CIRCULATION.
AB  - 1. The principal change in the peripheral blood consisted in the prolonged
      increase in number of the transitional white blood cells, an active brief
      stimulation of the polymorphonuclear neutrophils, which were later relatively
      decreased in number in four cases, in three dogs a late rise in number of the
      mononuclear and eosinophilic cells, and in one dog of mononuclear cells alone. 2.
      The normally high differential percentage count of polymorphonuclear eosinophils
      in dogs would be expected on account of the numerous parasitic infections which
      they usually have. 3. The splenorenal venous anastomosis offered a simple and
      satisfactory method of diverting the splenic blood into the general circulation
      because it was easy and produced no gross abnormal intraabdominal changes, and
      the vessels normally lay parallel to each other and were readily approximated
      without tension. 4. The operation was successful in every case. 5. The animals
      did very well after operation and were healthy and active. 6. No noteworthy
      histological changes were observed in any of the organs or tissues. 7. There was
      no essential change in bile production that could be detected by jaundice. 8. The
      urine and stools showed no changes.

PMID- 19868189
TI  - IDENTITY OF THE TOXINS OF DIFFERENT STRAINS OF BACILLUS WELCHII AND FACTORS
      INFLUENCING THEIR PRODUCTION IN VITRO.
AB  - Twenty-two additional strains of Bacillus welchii have been collected from widely
      different sources and tested with regard to toxin production. Each strain
      produces a toxin which, on animal inoculation, gives rise to lesions comparable
      in every respect to those produced by the toxins previously reported on, and each
      toxin was neutralized by an immune (antitoxic) serum produced with one of the
      former toxins. The toxins obtained from the several individual strains varied in
      potency, the lethal dose ranging from 0.3 to 3 cc. Experiments have been made to
      determine the influence of fresh muscle and glucose on toxin production and the
      relation of acidity to toxicity in the filtrates. It has been found that the
      addition of fresh muscle to the medium increases the potency of the toxin
      fivefold. Autoclaved muscle is without effect. Beef infusion broth containing 0.2
      to 1 per cent glucose gives a more potent product than sugar-free broth, while
      when higher percentages are employed the toxin production is lowered. There is no
      direct relation between acidity and toxicity, the most acid products manifesting
      little or no toxic action. In every medium used for culture the potency of the
      filtrates rapidly diminished after 24 hours' incubation, while the acidity
      increased or remained constant. The exception to this rule has been pointed out.
      The most active toxin is obtained by growing a virulent strain of the bacilli in
      a 0.2 or 0.3 per cent glucose broth to which fragments of fresh muscle have been
      added, and collecting the filtrate after from 18 to 24 hours' incubation. A
      review of the literature on the pathogenic effects and toxic products of Bacillus
      welchii and on the results of immunization of animals with the bacilli or toxic
      products does not indicate that the exotoxic nature of Bacillus welchii had been
      previously determined or an antitoxic serum in the true sense produced. The
      antitoxin for Bacillus welchii toxin can apparently be prepared from a single
      strain of the organism which yields under the conditions described a high titer
      of toxin, and this antitoxin can be employed to combat infection with or prevent
      infection by any strain whatever of the bacillus.

PMID- 19868190
TI  - THE EFFECT OF INJECTIONS OF HEMOLYTIC STREPTOCOCCI ON SUSCEPTIBLE AND
      INSUSCEPTIBLE ANIMALS.
AB  - 1. Streptococci injected into the circulation of cats are quickly withdrawn and
      are found most numerously in the lung, less numerously in the liver and spleen,
      and in small numbers in the bone marrow, lymph nodes, muscle, and kidney. 2. The
      streptococci taken up by the lung are killed within 5 to 8 hours, although they
      remain visible in films for a number of days. In the liver they are killed less
      rapidly, and in the spleen a few may remain viable for a considerable period. 3.
      This bactericidal action may be demonstrated in pieces of excised lung but not in
      lung extracts, and is apparently dependent on the action of the living cell. 4.
      Streptococci injected into a susceptible animal, the rabbit, are also promptly
      removed from the circulation, but are distributed in different proportions, the
      liver and spleen absorbing almost as many as the lung, and the muscles also
      taking up an appreciable number. 5. As in the cat, the organisms taken up by the
      lung and liver of the living rabbit are promptly killed. Those which lodge in the
      muscles, however, multiply rapidly. 6. About the time that the streptococci have
      begun to develop in the muscles (4 to 8 hours after injection) the number in the
      blood stream begins to increase. 7. The increase in the blood stream is not due
      to exhaustion of the mechanism of their removal nor have these organisms acquired
      a resistance sufficient to maintain them in the blood stream of a normal animal.
      The septicemia, then, is probably the resuit of washing out of organisms from the
      infected tissues. 8. Attempts to immunize rabbits have been unsuccessful, but in
      certain treated animals the distribution of the organisms among the various
      organs approached that found in insusceptible animals; i.e., cats.

PMID- 19868191
TI  - STUDIES OF LUNG VOLUME : III. TUBERCULOUS WOMEN.
AB  - The total capacity, middle capacity, and residual air have been determined in
      twenty adult women suffering from pulmonary tuberculosis. The chest volumes have
      been determined in each case and the normal lung volumes calculated by means of
      the ratios worked out in Paper I and applied to thirty-one men in Paper II. The
      excursions of the diaphragm have been determined by fluoroscopy in all cases. Of
      eight patients with incipient tuberculosis, five had lung capacities like those
      of men in the same group; i.e., about normal total capacity, slightly increased
      residual air, and consequently somewhat decreased vital capacity. Three had
      considerably diminished total capacity. In these three patients, however,
      clinical abnormalities were found (extensive miliary tuberculosis, obstruction of
      bronchus, fixation of diaphragm in expiratory position). In twelve patients with
      moderately advanced and advanced tuberculosis, the results agreed with those
      found in men, the total capacity and vital capacity being decreased, while the
      residual air was practically normal.

PMID- 19868192
TI  - THE SOLVENT ACTION OF ANTISEPTICS ON NECROTIC TISSUE.
AB  - 1. Dakin's hypochlorite solution has the power of dissolving necrotic tissue,
      pus, and plasma clot in the concentration and reaction used clinically. 2.
      Chloramine-T and dichloramine-T do not exhibit this action. 3. The solvent action
      of Dakin's hypochlorite solution of the degree of alkalinity used clinically is
      due primarily to its hypochlorite content, but its slight alkalinity, while in
      itself without solvent action, enhances the effectiveness of the hypochlorite. 4.
      In the degree of alkalinity used clinically, the solvent action of hypochlorite
      is absent below about 0.2 per cent sodium hypochlorite concentration. 5. The
      hypochlorite concentration at which the solvent action ceases is lower the more
      alkaline the solution, and vice versa. 6. None of the antiseptics studied had
      demonstrable solvent action on blood clot.

PMID- 19868193
TI  - COMMON COLDS AS A POSSIBLE SOURCE OF CONTAGION FOR LOBAR PNEUMONIA.
AB  - In two instances of common colds, with no known contact with cases of pneumonia,
      Pneumococcus Type I was found to be the predominating organism, which strongly
      suggests that it was the etiological agent in these colds. If this is so, common
      colds of this type must be looked upon as a possible source of contagion in the
      development of lobar pneumonia due to the Type I pneumococcus.

PMID- 19868194
TI  - A STUDY OF MITOCHONDRIA IN EXPERIMENTAL POLIOMYELITIS.
AB  - Typical mitochondria can be found in the spinal ganglion cells of monkeys with
      experimental poliomyelitis, even when typical Nissl substance has disappeared,
      and mitochondria-like structures are found in the remaining protoplasm in the
      latest stage of neurophagocytosis.

PMID- 19868195
TI  - THE LOCALIZATION OF STREPTOCOCCUS VIRIDANS.
AB  - The results of our experiments do not substantiate in full the theory of the
      power of selective action of Streptococcus viridans. A few strains showed a
      remarkable constancy in location and type of lesion, but these strains were
      greatly in the minority. The location of the lesions in animals seemed to bear no
      relation to the origin of the organism or to the lesions produced by it in the
      patient from which the strain was obtained. Streptococcus viridans, regardless of
      site of origin in the patient, produced most lesions in the heart and joints.

PMID- 19868196
TI  - MORPHINE HYPERGLYCEMIA IN DOGS WITH EXPERIMENTAL PANCREATIC DEFICIENCY.
AB  - The subcutaneous injection of 1 or 2 mg. of morphine sulfate per kilo
      subcutaneously in dogs with a pancreatic deficiency, whose sugar tolerance is
      still good, produces a rise in the glycemia about four times greater than the
      same amount of morphine calls forth in normal dogs. As dogs with a pancreatic
      deficiency due to coagulation or partial resection of the gland may legitimately
      be considered in a prediabetic state, the inference is warranted that the
      morphine test may be of value in detecting a weakened carbohydrate metabolism in
      the human subject. The test could easily and without danger be carried out with
      the micro methods now available for the quantitative determination of blood
      sugar. The experimental facts described in this paper give additional
      corroboration to the view that the response of a normal and of a pathologically
      altered organism to the same drug in the same dosage may be quantitatively very
      different.

PMID- 19868197
TI  - STUDIES OF LUNG VOLUME. I : RELATION BETWEEN THORAX SIZE AND LUNG VOLUME IN
      NORMAL ADULTS.

PMID- 19868198
TI  - STUDIES OF LUNG VOLUME : II. TUBERCULOUS MEN.
AB  - 1. The total capacity, middle capacity, and residual air have been determined in
      31 adult male patients suffering from tuberculosis of the lungs. 2. The chest
      volumes have been determined in each case and the normal lung volumes calculated
      by means of the ratios worked out in a previous paper. 3. In nine patients with
      incipient tuberculosis, the total lung volume was found within normal limits,
      whereas the vital capacity was diminished as a result of an increased residual
      air. The increase in the residual air was due to less complete expiration, caused
      partly by diminished movement of the diaphragm, partly by diminished compression
      of the chest wall. The diminished movement of the diaphragm was, as a rule, most
      marked on the most affected side. Whether these decreased movements are due to a
      reflex or to stiffness of the lung tissue we could not determine. The middle
      capacity was found practically normal. 4. In twenty-two cases of moderately
      advanced, and advanced tuberculosis, the total lung volume was in most cases
      markedly decreased. The vital capacity was substantially decreased, principally
      as a result of the diminished total capacity. The residual air was, as a rule,
      normal, although in a few cases an increase in residual air also contributed to
      the decrease in the vital capacity. The middle capacity, on which we do not want
      to put too much stress, was normal in some patients and considerably diminished
      in others.

PMID- 19868199
TI  - A NOTE ON THE PROGRESS OF CICATRIZATION OF WAR WOUNDS.
AB  - Some hypothetical conclusions bearing on the evolution of cicatricial tissue can
      be suggested. The arterial circulation deposits in the wound chemical substances
      necessary for contraction of the wound and for epithelial proliferation. When the
      biologic process is not hindered by any special or severe bacterial infection
      this deposit is as regular as the circulation itself, and enables us to determine
      in advance the date of cicatrization. It even seems as though when the
      epidermization process is retarded by a slight infection the substances necessary
      for epidermization are stored up in the wound, and when the delay due to
      infection is removed the epithelium finds an accumulation of nutritive
      substances, and, so to speak, makes up the lost time. Moreover, when an infection
      entirely or partially stops epidermization, we have observed (Experiments 3, 4,
      and 5) that after the infection has disappeared the progress of new
      epidermization is much more rapid than normally; it even passes the calculated
      curve. The infection apparently destroyed only the epithelium and left in the
      wound the chemical substances which activate epidermization. The existence of
      these physical or chemical activating agents has been indicated again by two
      anatomical clinical facts. In treating a scalp wound in which there had been
      practically no epidermization for many months, we applied over the entire surface
      of the sterile wound dermo-epidermic grafts of fetal skin. After apparently
      taking, the grafts were absorbed and disappeared, but epidermization of the
      periphery of the wound, which hitherto had not progressed, took place abundantly,
      almost a hundred times as much as before. We believe that by mathematical
      measurements we can solve the problem of the action of various organic fluids on
      the cicatrization of wounds.

PMID- 19868200
TI  - STUDIES OF OXYGEN IN THE VENOUS BLOOD : II. STUDIES OF THE OXYGEN UNSATURATION IN
      THE VENOUS BLOOD OF A GROUP OF PATIENTS WITH CIRCULATORY DISTURBANCES.
AB  - 1. Thirty-one determinations of the total oxygen-combining power and the oxygen
      in the venous blood from vena mediana cubiti of sixteen resting patients are
      reported. 2. The difference between the total oxygen capacity of the hemoglobin
      and the oxygen in the venous blood, the oxygen unsaturation, is calculated. 3. In
      twelve patients with compensated heart lesions the unsaturation was found within
      normal limits, between 2.5 and 8 volume per cent. 4. In four patients with
      incompensated heart disease the values for the unsaturation were all above the
      normal limit, from 9.7 to 15.2 volume per cent. 5. A general discussion of the
      problem of interpreting the results is given. 6. A comparison is drawn between
      the oxygen consumption calculated from direct determination of the blood flow on
      a normal subject (the writer) and the oxygen unsaturation determined 4 years
      later on the same subject. A close agreement between the two series of values
      exists.

PMID- 19868201
TI  - STUDIES OF OXYGEN IN THE VENOUS BLOOD : III. DETERMINATIONS ON FIVE PATIENTS WITH
      COMPENSATED CIRCULATORY DISTURBANCES.
AB  - 1. Forty-six determinations of the oxygen unsaturation, i.e., the difference
      between the venous oxygen and the total oxygen capacity of the hemoglobin, have
      been done in five patients with compensated circulatory disturbances. 2. Values
      within normal limits and near or below the normal average were found in four
      patients with regular pulse. 3. In one patient with mitral insufficiency and
      arrhythmia perpetua extremely varying values were encountered. Six determinations
      were made; in one instance the value was within normal limits, in five above, and
      in one of those even higher than in most cases of incompensated heart lesions. 4.
      A comparison is drawn between the directly determined oxygen unsaturation in
      these patients and the oxygen consumption calculated from previous experiments by
      the writer, where the blood flow was determined directly by the nitrous oxide
      method. A close parallelism is found.

PMID- 19868202
TI  - STUDIES OF OXYGEN IN THE VENOUS BLOOD : IV. DETERMINATIONS ON FIVE PATIENTS WITH
      INCOMPENSATED CIRCULATORY DISTURBANCES.
AB  - 1. A report is made of 103 determinations of the oxygen unsaturation of the
      venous blood of five patients with incompensated heart diseases. 2. Values for
      the oxygen unsaturation within normal limits were found only under two
      circumstances: (a) in a stage of full compensation, and (b) in a stage of
      incompensation where the symptoms were rapidly lessening. 3. Values above the
      upper normal extreme were met with under three circumstances: (a) during
      incompensation, (b) during compensation just before the clinical symptoms of
      incompensation had developed, and (c) at times in patients with auricular
      fibrillations in a condition of complete and stable compensation. 4. A comparison
      has been drawn between the directly found value for the oxygen unsatilration and
      the values for the oxygen consumption calculated from previous experiments by the
      writer on the blood flow (minute volume of the heart), in patients with similar
      clinical conditions. A close agreement existed. 5. It seems probable from our
      experience with patients under digitalis therapy that the oxygen unsaturation
      affords, an objective criterion of the positive effect of the therapy.

PMID- 19868203
TI  - THE FACTORS CONCERNED IN THE APPEARANCE OF NUCLEATED RED BLOOD CORPUSCLES IN THE
      PERIPHERAL BLOOD : I. INFLUENCE OF PROCEDURES DESIGNED TO INCREASE THE RATE OF
      BLOOD FLOW THROUGH THE BLOOD-FORMING ORGANS-EXERCISE AND NERVE SECTION.
AB  - 1. Increase in circulatory rate caused by hard exercise has no power to dislocate
      nucleated red cells from the bone marrow either in normal, in anemic, in
      hyperplastic, or in anemic and hyperplastic animals. 2. In anemic and
      hyperplastic animals pseudocrises of nucleated red cells can be produced at
      certain periods by hard exercise, but careful analysis leads inevitably to the
      conclusion that the increase in these cells is merely a more accurate expression
      of circulatory content at the time of the procedure. 3. Section of the vasomotor
      nerves to the four limbs with consequent dilatation of the marrow vessels and
      increased blood flow through the tissue does not result in the freeing of
      nucleated red cells from the bone marrow.

PMID- 19868204
TI  - SKIN FERMENTS.
AB  - That a definite change in the reactivity of the skin takes place during the
      transition from infancy to childhood has been repeatedly noted. Rolly (5),
      working with a variety of bacterial toxins, found that infants did not react, but
      that reactions occurred with advancing age. Similarly Tenner (6), using Witte's
      peptone, colon bacilli, and tuberculin observed that at about the period that the
      skin of children became increasingly sensitive to tuberculin, a corresponding
      reactivity was manifest toward the other antigens. It seems possible to us that
      this phenomenon is related to the alteration in the ferments of the skin that
      takes place during the transition period. Thus while the protease of the adult
      type of skin causes a definite autolysis, that of the fetal skin does not, the
      synthetic potential evidently predominating. Of greater significance seems to be
      the fact that the skin of the young animal contains peptidase to a considerable
      amount, while the adult skin seems to be without this ferment activity. If we
      assume that the disintegration of the native protein of the antigen is essential
      in eliciting certain skin tests, it would seem probable that the splitting would
      be less apt to take place in the young skin in which the lytic effects of the
      ferments are relatively suppressed. On the other hand, the young skin, containing
      peptidase, would be able to digest rapidly any antigen consisting of partially
      hydrolyzed proteins-as tuberculin-and in this way detoxicate and remove the
      noxious material. From these considerations the undoubted alteration of the skin
      reactivity taking place after infancy seems definitely correlated with changes in
      the proteolytic ferments. In how far they enter into and alter the specific
      reactions cannot be determined from the limited data so far available. Of the
      other ferments, the lipases, as pointed out by Porter, are possibly of importance
      in the resistance of the skin to tuberculous infection. It will be observed from
      the table that the activity of these skin ferments is less manifest in their
      action as esterases, on ethyl butyrate, than on the neutral fats used, oleic oil
      and butter fat, in this way differing from the activity of the serum. The
      relative resistance of the skin to tuberculous infection can, however, hardly be
      due to the activity of the lipase alone, for it must be kept in mind that the
      lepra bacillus, also rich in lipoids, is enabled to proliferate well within the
      epithelial tissues.

PMID- 19868205
TI  - INTRAVENOUS SEROTHERAPY OF WEIL'S DISEASE (SPIROCHAEETOSIS ICTEROHAEMORRHAGICA).

PMID- 19868206
TI  - DISTRIBUTION OF SPIROCHAETA ICTEROHAEMORRHAGIAE IN THE ORGANS AFTER INTRAVENOUS
      SERUM TREATMENT.
AB  - On the basis of these findings we believe that we are Justified in saying that
      the immune serum of Weil's disease is capable of destroying the spirochetes found
      within the organs in man, with the exception of the kidneys, and that the action
      of the serum upon the spirochetes is spirochetolytic and spirocheticidal. The
      scattered spirochetes in the kidney, on the other hand, are resistant to the
      action of the immune serum. The spirochetes disappear almost completely from the
      organs during the convalescent stage of Well's disease, even when no serum has
      been administered. The only organ to be excepted is again the kidney, but no
      comparison between .serum-treated and non-serum-treated cases should be made in
      this respect, for spirochetes are found numerously in the kidneys even with serum
      treatment. The disappearance of the spirochetes from the organs and tissues in
      Well's disease seems to be not so marked with the subcutaneous serum treatment as
      with the intravenous method, but the manner of their disappearance is about the
      same.

PMID- 19868207
TI  - THERAPEUTIC EXPERIMENTS WITH ROSENOW'S ANTIPOLIOMYELITIC SERUM.
AB  - Two series of experiments are described in which Rosenow's anti-poliomyelitic
      serum, so called, has been compared with the immune serum derived from monkeys
      which have convalesced or recovered from experimental poliomyelitis. The
      experiments consisted in introducing an active virus of polio-myelitis into the
      blood and of injecting the two kinds of serum into the cerebrospinal meninges
      according to the method of Flexner and Amoss. Under the conditions of the
      experiment, the control monkeys (a) receiving the virus intravenously alone do
      not develop paralysis, while those (b) receiving the virus intravenously and
      normal horse serum intraspinally develop paralysis. Moreover, the monkeys (c)
      receiving the virus intravenously and Rosenow's antipoliomyelitic serum
      intraspinally develop paralysis in the manner of those receiving normal horse
      serum intraspinally. The monkeys (d) which received the virus intravenously and
      the convalescent or immune monkey serum intraspinally alone did not develop
      paralysis. The Rosenow serum acts in the manner of normal horse serum; it
      promotes the passage of the virus of poliomyelitis from the blood into the
      nervous organs, and it does not protect from infection. We have found no evidence
      that Rosenow's serum under the conditions of the tests is effective
      therapeutically in monkeys or possesses antibodies of the same nature as those
      present in the blood of monkeys which have recovered from experimental
      poliomyelitis. Since the antibodies in convalescent poliomyelitic serum in man
      and the monkey are identical, it follows that any antibodies present in the
      Rosenow horse serum do not conform to those occurring in human convalescent
      serum.

PMID- 19868208
TI  - CULTIVATION EXPERIMENTS ON THE GLOBOID BODIES OF POLIOMYELITIS.
AB  - The globoid bodies, identical in morphological and cultural characteristics with
      the organisms described by Flexner and Noguchi, have been obtained in twenty-two
      cultures from the tissues of seven monkeys suffering from experimental
      poliomyelitis. Twenty of the strains were cultivated from the central nervous
      organs, all being obtained from the cerebrum except one, which was cultivated
      from the cervical portion of the spinal cord. Two strains were cultivated from
      the spleen. None of the cultivated strains inoculated produced typical
      poliomyelitis in monkeys. The recovery of a strain of the globoid bodies from the
      inoculated monkey is as difficult as is the original cultivation of the organisms
      from animals inoculated with the ordinary virus of poliomyelitis. Nothing in this
      study has served to implicate the streptococcus in the pathology of the
      poliomyelitic process; the streptococcus is, however, encountered as a common
      contaminant or secondary invader, especially in animals which have been etherized
      while moribund, or which had died some hours previous to the autopsy. When the
      infected and paralyzed animals are killed while still strong, secondary invading
      bacteria, including the streptococcus, tend to be absent from the tissues. A
      modified, perhaps improved, but alternative method has been devised for the
      cultivation of the globoid bodies and other microorganisms demanding a high
      degree of anaerobiosis.

PMID- 19868209
TI  - THE RELATION OF CIRCULATING ANTIBODIES TO SERUM DISEASE.
AB  - 1. The injection of horse serum either in small or in large amounts in human
      beings is always followed sooner or later by the development of
      hypersensitiveness of the skin to subsequent injections of horse serum. For the
      development of this reaction serum disease is not essential. 2. The blood serum
      of most patients who suffer from an attack of serum disease following injections
      of horse serum shows anaphylactin and precipitin for horse serum. 3. Anaphylactin
      and precipitin cannot be demonstrated in the blood serum of patients treated with
      horse serum who do not later present symptoms of serum sickness. 4. The
      appearance of anaphylactin and precipitin precedes shortly recovery from the
      disease. 5. With the appearance in the serum of antibodies to horse serum in
      great concentration, the antigen rapidly diminishes or disappears. 6. It is
      probable that the extrusion of these antibodies into the circulation is the
      result and not the cause of serum sickness. Their presence serves to neutralize
      or destroy the antigen and thus determines the recovery from serum sickness.

PMID- 19868210
TI  - IMMUNITY IN INTESTINAL OBSTRUCTION.
AB  - 1. There is no increased immunity or tolerance to intestinal obstruction after
      recovery from previous obstruction. 2. Dogs recovered from intestinal obstruction
      are not more resistant to injections of closed loop fluid than normal dogs. 3.
      Dogs injected with closed loop fluid are not more resistant to intestinal
      obstruction than normal dogs. 4. In dogs the normal variation in resistance both
      to intestinal obstruction and to the injection of closed loop fluid is large.

PMID- 19868211
TI  - THE ACTION OF ANTISEPTICS ON THE TOXIN OF BACILLUS WELCHII : A PRELIMINARY NOTE.
AB  - 1. Dakin's hypochlorite and chloramine-T solutions will protect pigeons against
      multiple fatal doses of the toxin of Bacillus welch when the antiseptic and the
      toxin are mixed in vitro and allowed to stand in contact for 5 minutes before
      injection. 2. The detoxicating action of the solutions is demonstrable also in
      the presence of serum. 3. Phenol solution, 0.25 per cent, has no such action.

PMID- 19868212
TI  - THE FACTORS CONCERNED IN THE APPEARANCE OF NUCLEATED RED BLOOD CORPUSCLES IN THE
      PERIPHERAL BLOOD : II. INFLUENCE OF PROCEDURES DESIGNED TO INCREASE THE RATE OF
      BLOOD FLOW THROUGH THE BLOOD-FORMING ORGANS-HEMORRHAGE AND INFUSION.
AB  - 1. Hemorrhage with immediate saline infusion causes the appearance in the
      peripheral blood of a slightly increased number of normoblasts provided
      normoblasts are already present in the blood stream. Marrow hyperplasia does not
      intensify this reaction and the cells found probably do not leave the marrow pulp
      but are in the blood stream at the time of the experiment. 2. The slight increase
      in cells occurring immediately after hemorrhage and infusion is designated a
      pseudocrisis. True crises are much more extensive; they tend to occur just before
      rapid increase in the erythrocyte count and usually towards the end of the 1st
      week following hemorrhage. 3. Red cells and white cells tend to move from the
      marrow together, but this association is not invariable. 4. After repeated
      hemorrhages regeneration occurs independently of the appearance of nucleated red
      cells in the peripheral blood. 5. Repeated hemorrhages associated with extension
      of erythrocyteproducing marrow lead to polycythemia but not to a conspicuous
      increase in speed of regeneration.

PMID- 19868213
TI  - THE MORPHOLOGICAL CHANGES IN THE TISSUES OF THE RABBIT AS A RESULT OF REDUCED
      OXIDATION.
AB  - Exposure of rabbits to an atmosphere of low oxygen content results in a
      stimulation of the cardiorespiratory systems, in an extension (hyperplasia) of
      red bone marrow and probably of a thyroid hyperplasia, with the further
      production of hydropic and hyaline degeneration in the cells of the
      parenchymatous organs. An atmosphere of high carbon dioxide and normal oxygen
      content produces, however, a stimulation of the cardiorespiratory systems, but no
      marrow extension and, in the concentrations used, but slight hydropic
      degeneration in the parenchyma of the glandular organs.

PMID- 19868214
TI  - EXPERIMENTAL ACUTE NEPHRITIS : A STUDY OF THE ACIDOSIS, NITROGEN AND CHLORIDE
      RETENTION, AND OF THE PROTECTIVE ACTION OF SODIUM BICARBONATE.
AB  - 1. In experimental nephritis caused by cantharidin, arsenic, diphtheria toxin,
      and potassium chromate, in addition to the retention of the non-protein and urea
      nitrogen and of the chlorides in blood, an acidosis occurs. 2. Sodium bicarbonate
      given by the stomach has the power of diminishing the acidosis in these types of
      nephritis. 3. The degree of increase in the non-protein and urea nitrogen content
      in the blood in mild nephritis varies considerably in different dogs receiving
      the same dose per kilo of a given poison. 4. Histological examination shows
      little if any influence resulting from the administration of sodium bicarbonate
      upon the grade of the nephritis induced by the poisons.

PMID- 19868215
TI  - FURTHER STUDIES ON THE PROPERTIES OF PURE VACCINE VIRUS CULTIVATED IN VIVO.
AB  - 1. The virulence of vaccine virus for the testicular tissues increases until its
      maximum is finally reached. The selective increase is not associated with any
      loss, reduction, or modification in its virulence for the skin. A highly potent
      testicular vaccine is also highly active for the skin. 2. The testicular strain
      of vaccine virus has no more tendency to localize in various organs than the
      ordinary skin strain. Both may localize in adjacent lymph nodes when introduced
      intravenously, subcutaneously, or intratesticularly in sufficiently large
      quantities, but other organs are not involved. 3. Intravenous inoculation of an
      excessive amount of a powerful vaccine virus (1 to 2 cc. of undiluted stock
      emulsion), irrespective of whether it is from the testis or the skin, will result
      in a generalized eruption over the entire body surface of rabbits. The eruption
      may be confluent on mucous membranes of the mouth, nostrils, genitalia, etc.
      Intratesticular or subcutaneous inoculations of the same virus fail to produce
      this effect. 4. Subcutaneous or intravenous introduction of much smaller
      quantities of the virus does not cause an appreciable local or general reaction
      in the rabbit. But the animals which have once received these injections become
      refractory to a subsequent vaccination as applied to the skin. It seems probable
      that an active immunity has been conferred. 5. Experiments on the viability and
      resistance of the testicular strain of vaccine virus indicate that the virus is
      best preserved when emulsified with Ringer's solution or 0.9 per cent saline
      solution. Distilled water, while apparently one of the best diluents, fails to
      keep the virus active as long as Ringer's or saline solutions. As would be
      expected, the lower the temperature is, the longer the virus retains its
      viability. At 18 degrees or 37 degrees C., the deterioration of the virus
      proceeds rapidly. However, a small part of the virus survives after many weeks'
      standing at 37 degrees C. 6. Of the two most commonly employed chemical agents
      for the ripening (eliminating bacteria) process of the green vaccine pulp,
      glycerol and phenol, the latter is the less injurious. Phenol in concentration
      above 2 per cent destroys the virus within 24 hours at any temperature, but it
      has almost no injurious effect when used in 0.5 to 1 per cent. On the other hand,
      glycerol is a powerful vaccinicide. When used in full strength it destroys the
      virus within 24 hours, even at 4 degrees C. In a concentration of 40 per cent,
      that ordinarily recommended for the ripening, the virus retains some of its
      virulence for about half a year at 4 degrees C., while at higher temperatures the
      same concentration kills the virus within 1 to 2 months. The virus preserved in
      distilled water or Ringer's solution under similar temperature conditions remains
      more active during this period. From this it may be concluded that glycerol is
      not an indifferent agent, as is assumed by many, but a powerful vaccinicide when
      used in high concentrations. The injurious effect is markedly accelerated at 18
      degrees or 37 degrees C. 7. The vaccine virus retains its virulence better in a
      sealed tube containing either hydrogen, nitrogen, or air than in an open
      receptacle. The virus deteriorates when placed in a sealed tube with oxygen or
      carbon dioxide. 8. Desiccation decreases to a considerable degree the virulence
      of the vaccine virus. In the dried state the virus retains its viability about as
      long as does the emulsion, but it is not protected from the deterioration caused
      by age under various conditions. 9. Iodine is a powerful disinfectant for the
      vaccine virus, but its sodium and potassium salts have no effect. Various bile
      salts destroy the vaccine virus when employed in sufficient concentration.

PMID- 19868216
TI  - SURVIVAL OF POLIOMYELITIC VIRUS IN THE BRAIN OF THE RABBIT.
AB  - Suspensions of the central nervous tissues of monkeys, containing the active
      filterable virus of poliomyelitis, may be injected into the brain of rabbits
      without setting up symptoms, provided the volume of injection does not cause
      dangerous increased intracranial pressure. Aside from the pressure effects which
      develop quickly, no other symptoms or pathological lesions are produced by the
      suspensions. The active virus of poliomyelitis survives in the brain of rabbits
      for 4 days, as determined by tests in the monkey, into which the excised site of
      injection in the rabbit brain is reinoculated. It cannot be detected by this test
      after the expiration of 7 days. The virus of poliomyelitis is unadapted to the
      rabbit, and neither induces lesions nor survives long in the central nervous
      organs of that animal. In this respect it differs from certain streptococci
      cultivated from poliomyelitic tissues. A monkey immunized to streptococcus
      cultivated from human poliomyelitic nervous tissues yielded a serum which
      agglutinated the streptococcus in high dilution, but was without neutralizing
      action on the filtered virus; and the streptococcus-immune monkey was not
      protected against the effects of an intracerebral inoculation of the filtered
      virus. The experiments recorded provide additional reasons for concluding that
      the streptococcus cultivated from cases of poliomyelitis differs essentially from
      the filterable virus and is not the microbic cause of epidemic poliomyelitis.

PMID- 19868217
TI  - A STUDY OF THE NITROGEN METABOLISM AND OF ACIDOSIS AFTER THE TRANSPLANTATION OF A
      URETER INTO THE DUODENUM IN DOGS.
AB  - 1. The present work was undertaken to study the metabolism in the dog after a
      ureter-intestinal transplantation. Four dogs, Nos. I, 2, 5, and 7, were
      originally operated upon. Two, Nos. 2 and 7, showed kidney infection; the other
      two were not infected, and in these the metabolism was studied; one of the latter
      (No. 1) showed marked hydronephrosis and hydroureter. 2. Both after the
      transplantation of the right ureter into the intestine and the ligation of the
      right ureter, there is generally a moderately increased output of nitrogen in the
      urine and, in the former instance especially, a retention of nitrogen in the
      blood, but no change in carbon dioxide content in the blood. The significance of
      this is probably an increased tissue catabolism, the cause of which is doubtful
      without further work. 3. After removal of the left kidney subsequent to
      transplantation of the right ureter into the duodenum, renal insufficiency and
      resulting retention developed. The non-protein and urea nitrogen in the blood
      steadily increased and the carbon dioxide content of the blood diminished to the
      level characteristic of a moderate acidosis. No ketones were found in the blood
      The dogs died 5 to 10 days after the nephrectomy under conditions characteristic
      of suspended renal activity-deep respiration, unconsciousness, and sopor.

PMID- 19868218
TI  - METHOD FOR INTRAVENOUS INJECTION OF GUINEA PIGS.

PMID- 19868219
TI  - A STUDY OF THE ANTISEPTIC PROPERTIES OF CERTAIN ORGANIC COMPOUNDS.
AB  - THIS STUDY OF THE INHIBITIVE EFFECT OF ANILINE AND SOME OF ITS DERIVATIVES AND OF
      THE TRIPHENYLMETHANE DYES ON CERTAIN BACTERIA WARRANTS THE FOLLOWING TENTATIVE
      CONCLUSIONS: 1. The composition and reaction of the medium exert a marked
      influence on the behavior of the antiseptic. The higher the concentration of
      organic nitrogenous compounds (peptone) in the medium, the lower is the effective
      concentration of the dye. The reaction of the medium modifies the specific action
      of the antiseptic, owing probably to an alteration in the bacterial cell. 2. The
      germicidal action of the compounds is a function of the benzene nucleus, the
      added elements or radicals, their number, and, in the case of the dyes, probably
      the quinoid structure of the nucleus. 3. As far as tested, the increase in the
      number of alkyl radicals increases the antiseptic power. Methyl green is an
      interesting exception to this rule, for the change of one of the nitrogens to the
      quaternary salt is accompanied by an almost complete loss in inhibitive action.
      4. The antiseptic power is enhanced to a greater extent by an ethyl than a methyl
      group, and the second alkyl produces a proportionately greater increase than the
      first. It appears that the relative position of the introduced group may be a
      factor in determining the relative improvement in the effectiveness of the
      compound. 5. The introduction of a methyl group in the nucleus consistently
      enhances the inhibitive action of the compound and its alkyl derivatives. This is
      evident from a comparison of the action of aniline and its derivatives with that
      of toluidine and its corresponding derivatives. 6. The simple aniline
      derivatives, as well as the dyes, are more toxic for the Gram-positive than the
      Gram-negative bacteria. Of the former, Bacillus subtilis is more sensitive to the
      dyes than Staphylococcus aureus, while the reverse is true in the case of the
      aniline compounds. 7. The most marked specific selective effect is manifested by
      the triphenylmethane dyes. Bacillus aerogenes and Bacillus typhosus possess a
      higher resistance to these substances than Bacillus coli or Bacfflus dysenterice.
      The last is exceedingly sensitive. This partial specificity is apparently a
      function of the molecule as a whole.

PMID- 19868220
TI  - THE ELIMINATION OF IRON AND ITS DISTRIBUTION IN THE LIVER AND SPLEEN IN
      EXPERIMENTAL ANEMIA. II.
AB  - In the continuous blood destruction, essentially a chronic experimental anemia,
      caused by injecting the dog with Trypanosoma equiperdum, no increased elimination
      of iron is observed in the feces. The storage of iron in the liver and spleen
      under these experimental conditions is somewhat greater in amount, but of the
      same general character as in transient experimental anemia. Splenectomy before or
      after infection, i.e. the development of anemia, influences neither the
      elimination of iron in the feces nor its storage in the liver. The retardation of
      the course of the trypanosome infection and thus the production of a more chronic
      anemia by treatment with a trypanocide, arsenobenzol, likewise does not affect
      iron storage. These experiments have therefore failed to reproduce the changes in
      iron metabolism seen in certain of the chronic hemolytic anemias of man. In the
      presence of a bile duct-ureter fistula the iroh content of the mixture of urine
      and bile is not appreciably greater than that of the urine alone. In the dog,
      therefore, the elimination of iron in the the bile would not appear to be an
      important factor. On the other hand, when bile is excluded from the intestine an
      unusual storage of iron occurs in the spleen. For this no explanation is offered.

PMID- 19868221
TI  - A STUDY OF THE BLOOD PRESSURE BY THE METHOD OF GAERTNER, ESPECIALLY IN PATIENTS
      SUFFERING FROM FIBRILLATION OF THE AURICLES.
AB  - The function of the arteries as an elastic reservoir between the heart and the
      capillaries is reviewed. The appropriateness of selecting the exit from this
      reservoir as the point for estimating its effective pressure is shown. The
      technique for taking the pressure here by the method of Gaertner is described and
      its advantage and certain apparent disadvantages are indicated. The technique of
      Gaertner is shown to be especially applicable to the study of the blood pressure
      in fibrillation of the auricles. The use of this technique has brought out a
      defect in the so called fractional method of taking the pressure in this
      condition; the brachial and digital curves cross. Taking pressure of both
      brachial and digital arteries has shown that certain different types exist;
      first, that in which both central and peripheral pressures are stable; second,
      that in which the more central pressure is stable and the peripheral pressure
      fluctuates; and third, that in which both pressures fluctuate together.

PMID- 19868222
TI  - THE PERIPHERAL BLOOD PRESSURE IN FIBRILLATION OF THE AURICLES.
AB  - 1. Experiments on dogs show that whereas the pulse pressure in the larger
      arteries (femoral) varies extensively, it varies within narrow limits only in the
      small ones (dorsal artery of the foot). These results supply an experimental
      explanation for the fact that in man uniform pressure readings were obtained by
      Gaertner's method at the digital artery. 2. The experiments show likewise that in
      certain instances the level of pressure is maintained when fibrillation of the
      auricles sets in. It is therefore clear that when the mechanism of the heart beat
      in man changes to fibrillation of the auricles, a change, that is a fall, in
      pressure need not necessarily develop.

PMID- 19868223
TI  - FREE ANTIGEN AND ANTIBODY CIRCULATING TOGETHER IN LARGE AMOUNTS (HEMAGGLUTININ
      AND AGGLUTINOGEN IN THE BLOOD OF TRANSFUSED RABBITS).
AB  - In rabbits transfused almost daily with the whole citrated blood of other
      rabbits, an extraordinary condition often develops, which manifests itself in an
      almost immediate clumping together of all the red cells in specimens of the shed
      blood. This clumping is due to one or more true agglutinins, of which the
      strength may be such as to cause clumping in a 1: 2,800 plasma dilution. The
      agglutinating principle circulates with the corpuscles against which it is
      effective; but under ordinary circumstances intravascular clumping fails to occur
      because the union of antigen and antibody can take place only at a temperature
      several degrees below that of the body. If the temperature is sufficiently
      lowered, as when a tourniquet is applied to the rabbit's ear, intravascular
      clumping ensues. In defibrinated blood, gradually cooled, clumping is first noted
      as the temperature of 35 degrees C. is approached; and at room temperature (22
      degrees ) the corpuscles will often come together in a short time into a single,
      solid mass. At 0 degrees C. the agglutination is still more marked. The reaction
      seems to be completely reversible, for when the blood is warmed again, the clumps
      break up and disappear at between 35 degrees and 36 degrees C. Cooling and
      warming with the resultant clumping and dissociation can be carried out many
      times on the same blood specimen without apparent change in the corpuscles or in
      the rapidity of the reaction. The response to temperature changes is extremely
      prompt. Once it has been elicited, the agglutinating principle may persist for a
      long time after the transfusions are stopped, in one instance it was still strong
      133 days after the last transfusion. During this period the plethora was
      succeeded by a severe anemia, which in turn was recovered from. In many rabbits
      no agglutinin develops, and a continuance of the transfusions will not elicit it.
      Indeed, when present it tends to disappear if the transfusions are persisted in.
      In several of the animals in which the agglutinin was strongest, the plethora was
      suddenly succeeded by severe anemia, despite continued transfusions. The
      character of the temperature control of the agglutination, which somewhat
      resembles that of the hemolysin in paroxysmal hemoglobinuria, has led us to
      consider whether the blood destruction might not be due to accidental chilling of
      the animal. Efforts to induce a fall in the hemoglobin by placing the rabbit's
      ear in ice water have as yet been unsuccessful. Thus far no adequate search for
      an hemolysin has been made. The object of the present paper has been to describe
      a condition in which large amounts of free antigen and antibody circulate
      together in the organism, and to demonstrate the factor which prevents their
      union, the results of which could easily be fatal. The causes of the condition
      will be dealt with in a subsequent communication.

PMID- 19868224
TI  - A STUDY OF ACUTE MERCURIC CHLORIDE INTOXICATIONS IN THE DOG WITH SPECIAL
      REFERENCE TO THE KIDNEY INJURY.
AB  - A study of the experiments comprising the first group of animals permits the
      deduction that these animals succumb to the acute poisoning as a result of the
      shock which the poison induces through its corrosive action in the stomach and
      intestine. The animals die before the mercury, acting as such during its
      elimination by the kidney, can induce an acute nephropathy and before the
      mercury, by inducing an acid intoxication, can lead to an acute kidney injury.
      The remaining animals of the series, Groups II, III, and IV, have withstood the
      corrosive action of the poison. These animals have shown the same type of delayed
      intoxication from the poison. The intoxication, however, has varied in time of
      appearance, duration, and severity. The animals classified as Group II have
      developed during the stage of improvement from the gastroenteritis a rapid and
      severe type of acid intoxication, have become rapidly anuric, and have died
      either in a state of air-hunger or in convulsions. The animals of Group III,
      either during or after their recovery from the gastroenteritis, have developed a
      mild grade of acid intoxication. During the following days of the experiments the
      animals succeeded in reestablishing their normal acid-base equilibrium. All the
      animals of this group recovered. The animals of Group IV have shown a recovery
      from the mercury enteritis. Following a period during which there was an attempt
      on the part of the animals to return to normal, as indicated by an increase in
      the alkali reserve of the blood and by an increased output of
      phenolsulfonephthalein and urine, the members of the group developed a delayed
      acid intoxication, and, like the animals of Group II, became anuric.

PMID- 19868225
TI  - A STUDY OF THE LOW BLOOD PRESSURES ASSOCIATED WITH ANAPHYLACTIC AND PEPTONE SHOCK
      AND EXPERIMENTAL FAT EMBOLISM, WITH SPECIAL. REFERENCE TO SURGICAL SHOCK.
AB  - 1. In peptone shock there is a marked, precipitate fall in arterial pressure. At
      the same time there is a fall in venous pressure. 2. In experimental fat
      embolism, (a) the fall in blood pressure is always gradual; (b) approximately 1
      cc. of oil for each pound of body weight must be injected before a lasting fall
      in arterial pressure is produced; (c) it makes only a slight difference whether
      this amount is injected in small doses at a time or in relatively large
      quantities; and (d) when the arterial pressure falls, but not till then, the
      venous pressure rises. 3. In peptone shock, dyspnea, by its suction and force
      pump action upon the reservoir of stagnating blood in the liver, brings more
      blood to the heart and causes a rise in arterial pressure. By repeatedly inducing
      short periods of dyspnea at frequent intervals, permanently beneficial results
      are obtained and the life of the animal can be saved. 4. In experimental fat
      embolism, dyspnea will cause a rise in blood pressure. But permanently beneficial
      results have not been obtained by this method. If dyspnea is found to bring
      permanent improvement in surgical shock, it is indirect evidence that this
      condition is not due to fat embolism. Respiratory suction is probably not
      responsible for the rise in blood pressure in experimental fat embolism. It seems
      more likely that the dyspnea in some way facilitates the passage of blood through
      the embarrassed pulmonary circulation. Artificial respiration with a bellows will
      also frequently cause a rise in blood pressure in experimental fat embolism. 5.
      In peptone shock the respiration is usually not affected, although there is some
      evidence that the respiratory center may be in a state of increased irritability.
      In experimental fat embolism, in some animals a violent dyspnea develops
      spontaneously. This is usually accompanied by edema of the lungs. In other
      instances, an apnea occurs, even before the blood pressure has begun to decline.

PMID- 19868226
TI  - EXPERIMENTS OUTLINING THE LIMITATIONS OF OPERATIONS ON THE ABDOMINAL AORTA.
AB  - 1. Injuries of the abdominal aorta in dogs may be corrected with subsequent
      perfect restoration of the continuity of the vessel. 2. The complete occlusion of
      the aorta for a period of 30 minutes is not necessarily followed by serious
      consequences. 3. In cases in which a portion of the aorta must be resected, an
      arterial segment taken from another animal can be safely utilized as a
      transplant. 4. While the reestablishment of the continuity of the severed aorta
      by the circular suture is possible, the approximation of the severed ends during
      the suture entails such injury that thrombosis frequently occurs. Therefore, when
      the aorta is completely severed, the introduction of a transplanted segment is
      indicated. 5. An arterial tube of increased caliber made of smaller vessels such
      as the carotid lends itself readily as a transplant to the severed aorta, with a
      reasonable assurance of reestablishing the continuity of this vessel. 6. Defects
      in the aorta can be readily corrected by the use of fascial transplants with a
      minimum danger of thrombosis.

PMID- 19868227
TI  - MORPHOLOGICAL CHARACTERISTICS AND NOMENCLATURE OF LEPTOSPIRA (SPIROCHAETA)
      ICTEROHAEMORRHAGIAE (INADA AND IDO).
AB  - The present study deals with the morphology and systematic position of the
      causative agent of infectious jaundice. There are several features which are not
      found in any of the hitherto known genera of Spirochaetoidea which led me to give
      this organism an independent generic name, Leptospira, denoting the peculiar
      minute elementary spirals running throughout the body. The absence of a definite
      terminal flagellum or any flagella, and the remarkable flexibility of the
      terminal or caudal portion of the organism are other distinguishing features.
      Unlike all other so called spirochetes the present organism resists the
      destructive action of 10 per cent saponin. A detailed comparative study of
      related genera, including Spirochaeta, Saprospira, Cristispira, Spironema, and
      Treponema, has been given with the view of bringing out more strongly the
      contrast between them and the new genus. A study has been made to discover
      whether any differential features exist among the strains of Leptospira
      icterohaemorrhagiae derived from the American, Japanese, and European sources,
      but none has been found. It is hoped that the creation of a new genus may
      facilitate a more exact morphological description than has hitherto been
      possible, due to the vague use of the term Spirochaeta which indiscriminately
      covered at least six large genera of spiral organisms.

PMID- 19868228
TI  - FURTHER STUDY ON THE CULTURAL CONDITIONS OF LEPTOSPIRA (SPIROCHAETA)
      ICTEROHAEMORRHAGIAE.
AB  - 1. The presence of suitable animal or human serum is essential for the
      cultivation of Leptospira icterohaemorrhagiae. 2. The nutrient value of serum is
      considerably reduced by heating to 60 degrees C. for 30 minutes and is destroyed
      by boiling (100 degrees C). Filtration through a Berkefeld filter does not
      diminish the nutrient value of the serum. 3. The cultural value of different
      animal sera varies considerably. It is entirely absent from the sera of the rat
      and the pig. The sera of the rabbit, horse, and goat are better suited for the
      growth of the organism than those of the guinea pig, sheep, donkey, or calf.
      Human serum is suitable, but not ascitic fluid. 4. Fresh or heated emulsions of
      the liver, kidney, heart muscle, or testicle of the normal guinea pig or rabbit
      have no cultural value for the organism. The same may be said of both the white
      and yolk of the hen's egg. 5. A luxuriant growth takes place in a medium of
      Ringer's solution to which more than 10 per cent of normal rabbit serum is added.
      There is only moderate growth with 5 per cent of serum, and none when less than 2
      per cent is present. The use of an undiluted serum offers no advantage over a
      diluted one, provided the latter contains at least 10 per cent of serum. In the
      case of certain animal sera dilution seems to make them more suitable for
      cultivation purposes, owing perhaps to its reduction of their inherent
      alkalinity. 6. The tonicity of the culture medium has but little influence upon
      the growth and morphology of the organism. A medium containing distilled water as
      diluent or one containing 8 per cent sodium chloride seems to give identical
      results. The viability of the organism was greatest in a medium in which Ringer's
      solution or isotonic salt solution was used as diluent. 7. The reaction of the
      medium is an important factor in the cultivation of the organism, which thrives
      most vigorously in a medium of which the reaction is slightly alkaline, not
      exceeding that of the serum. If the reaction is neutral, the growth is meager,
      and the culture is short lived. When the reaction of a medium becomes alkaline by
      the addition of a small amount of sodium hydroxide, or faintly acid by the
      addition of a little hydrochloric acid, no growth can take place. 8. Leptospira
      icterohaemorrhagiae is an obligatory aerobe. Any hindrance to the access of
      oxygen constitutes an unfavorable factor in obtaining a culture. 9. The addition
      of carbohydrates to media has no perceptible effect upon the growth or morphology
      of the organism. The reaction of the media is not modified by their presence. 10.
      Leptospira icterohaemorrhagiae grows at any temperature between 37 degrees and 10
      degrees C., the optimum zone being 30-37 degrees C. Growth proceeds more rapidly
      at 37 degrees C. than at 30 degrees or at 25 degrees , but the cultures remain
      viable much longer at the latter temperatures. No growth takes place at 42
      degrees C. 11. Three different media are described for the cultivation of freshly
      isolated strains. After prolonged cultivation on these media a strain may be
      readily cultivated in a serum diluted with Ringer's or isotonic salt solution.

PMID- 19868229
TI  - THE SURVIVAL OF LEPTOSPIRA (SPIROCHAETA) ICTEROHAEMORRHAGIAE IN NATURE;
      OBSERVATIONS CONCERNING MICROCHEMICAL REACTIONS AND INTERMEDIARY HOSTS.
AB  - 1. Leptospira icterohaemorrhagiae is unable to grow in the urine, either with or
      without the addition of suitable culture ingredients, the acidity of the urine
      being detrimental to the growth. It survives less than 24 hours, unless the urine
      is neutralized or slightly alkalized, when the period of survival is somewhat
      longer. If suitable nutrient ingredients are added to the neutralized or slightly
      alkalized urine, the organism is able to grow for about 10 days, after which
      multiplication ceases. 2. Feces from normal or jaundiced persons destroy
      Leptospira icterohaemorrhagiae within 24 hours when a rich culture is added and
      the mixture allowed to stand at 26 degrees C. The addition of blood serum and
      corpuscles does not prevent the destruction of the organism. Autoclaved specimens
      and filtrates of unheated feces do not constitute a suitable medium in which to
      keep the organism alive for any length of time, but the addition of blood
      corpuscles and serum in adequate quantities renders them fairly satisfactory as
      media. Under natural conditions Leptospira icterohaemorrhagiae cast off in the
      feces cannot survive more than 24 hours. 3. Polluted water, sewage, and soil will
      not serve to keep Leptospira icterohaemorrhagiae alive for more than 3 days at
      the most. When deprived by filtration or autoclaving of their bacteria they
      become indifferent diluents and may be used to make up a culture medium when
      mixed with serum and citrate plasma of a suitable animal. Sterilized soil with a
      neutral reaction, when added to a culture, has an unfavorable effect upon the
      growth of the organism. 4. Most of the aerobic bacteria found in feces, sewage,
      soil, and tap water inhibit the growth of Leptospira icterohaemorrhagiae when
      inoculated into the same medium. Bacillus faecalis alkaligenes and many strains
      of non-hemolytic streptococci caused the least interference, although growth was
      never so vigorous or lasting in the media in which they were present as in the
      control media. Certain pathogenic bacteria (Bacillus typhosus, Bacillus
      paratyphosus, Bacillus dysenteriae, pneumococcus) are antagonistic to the growth
      of the spirochete. 5. Leptospira icterohaemorrhagiae is highly sensitive to the
      destructive action of bile, bile salts, and sodium oleate, but resists the action
      of saponin. In this last respect it differs from many so called spirochetes. The
      destructive action of these agents is counteracted by blood serum. 6. The larvae
      and adults of the Culex mosquito, the larvae of the house-fly and bluebottle fly,
      wood ticks (Dermacentor andersoni), and leeches failed to become carriers of the
      spirochetes when fed on infected guinea pigs or their organs; that is, they
      cannot play the part of an intermediary host of Leptospira icterohaemorrhagiae.

PMID- 19868230
TI  - BEHAVIOR OF HYPOCHLORITE AND OF CHLORAMINE-T SOLUTIONS IN CONTACT WITH NECROTIC
      AND NORMAL TISSUES IN VIVO.
AB  - 1. The fall in chlorine concentration of Dakin's hypochlorite solution is more
      rapid in contact with necrotic than in contact with normal tissue. 2. The fall in
      chlorine concentration of chloramine-T solution is very slight when applied to
      necrotic tissue and is negligible when applied to normal tissue. 3. The action of
      the hypochlorite solution on tissue results in the separation of particles of
      necrotic tissue, hair, epithelial scales, coagulated serum, etc., and a gradual
      digestion of these substances, taking place over a period of at least 17 hours.
      4. The fall in the chlorine concentration of the hypochlorite solution is not
      complete until the particles are completely dissolved. 5. Chloramine-T solution,
      2 per cent, has no erosive effect comparable with that exhibited by the
      hypochlorite solution. 6. Repeated exposures to the three solutions show the
      hypochlorite solution to be superior in its cleansing ability on necrotic tissue.
      7. The hypochlorite solution is much more irritating to normal rabbit skin than
      chloramine-T solution or the alkaline control solution. 8. Therefore, the
      irritating effects must be due to the readily available chlorine.

PMID- 19868231
TI  - TOXICITY OF CERTAIN WIDELY USED ANTISEPTICS.
AB  - 1. The substances injected intraperitoneally into mice and guinea pigs arranged
      in the order of their decreasing toxicity are: eucalyptol and brilliant green;
      mercurophen; mercuric chloride and chloramine-T; dichloramine-T and proflavine;
      hychlorite, Dakin's hypochlorite, Javelle water, and magnesium hypochlorite;
      iodine and phenol. 2. Now that Dakin's bland solvent, chlorcosane, is available
      as a vehicle for dichloramine-T, eucalyptol should probably be discarded for this
      purpose because of its much greater toxicity. 3. Inasmuch as experienced surgeons
      do not approve of the injection of solutions of iodine and phenol into closed
      cavities, it would seem advisable not to use any of the antiseptics here
      discussed in this manner inasmuch as all exhibit a greater toxicity for mice and
      guinea pigs than the two chemicals first named. 4. The method of testing toxicity
      of antiseptics by subcutaneous injection is not satisfactory because exudation
      and subsequent sloughing reduce the rate of absorption and make uncertain the
      amount finally absorbed.

PMID- 19868232
TI  - THE EFFECT OF PAINTING THE PANCREAS WITH ADRENALIN UPON HYPERGLYCEMIA AND
      GLYCOSURIA.
AB  - After Blum's discovery of the production of glycosuria by the subcutaneous
      injection of adrenal extract, Herter has the merit of having found that injection
      of adrenalin into the peritoneal cavity also produces glycosuria; this is an
      undeniable fact. Concerning Herter's claim that intraperitoneal injection gives a
      higher degree of glycosuria than subcutaneous or intravenous injection, we offer
      no comment since we have made no observations on the glycosuric effect of
      subcutaneous injection of adrenalin, while we have made only three experiments by
      intraperitoneal injection. The most we can predicate on the basis of the present
      experiments is that intraperitoneal injection of adrenalin produces a somewhat
      higher degree of glycosuria than could be anticipated. However, in an earlier
      study carried out several years ago we arrived at the conception that the more
      slowly adrenalin was absorbed from the tissues into the circulation, the greater
      was its glycosuric effect; hence an intramuscular injection, which in its effect
      is nearly equal to that of an intravenous injection, induced a glycosuria
      definitely smaller than that set up by a similar dose administered
      subcutaneously. Unless the absorption from the peritoneal cavity is shown to be
      different from the absorption from subcutaneous injections, there could be no
      reason to assume that the glycosuric effect of intraperitoneal injection is much
      greater than that of subcutaneous injection. We might add that our former
      experiments do not support Herter's view that subcutaneous injection of adrenalin
      yields only slight degrees of glycosuria, because it is largely oxidized before
      entering the circulation. A difference exists in the effects upon blood pressure
      and upon sugar production, depending upon the mode of administration of
      adrenalin. With regard to the sugar production, a subcutaneous injection has a
      definitely greater effect than an intravenous injection; with regard to the blood
      pressure effect, however, the opposite is true. Herter states that an
      intraperitoneal injection of adrenalin exerts a smaller effect upon blood
      pressure than an intravenous injection-a fact which Auer and Meltzer can confirm
      for the rabbit. Our experiments lead us to conclusions which do not conform to
      those of Herter. It will be recalled that Herter and his coworkers state first,
      that painting the pancreas causes a marked glycosuria and hyperglycemia, and,
      second, that the glycosuria and hyperglycemia produced by intraperitoneal
      injections are of pancreatic origin; that is, they are produced by the
      adrenalin's coming in contact with the pancreas. In our experiments tabulated in
      Table IV, in which the pancreas was isolated from the rest of the peritoneal
      cavity, the glycosuria was about one-third, and the rise in blood sugar about two
      thirds that obtained by painting the unisolated pancreas. Hence two facts may be
      deduced: first, that the painting of the isolated pancreas produces only mild
      glycosuria and hyperglycemia, and, second, that the greater production of sugar
      observed after the painting of the unisolated pancreas cannot be of pancreatic
      origin. Indeed, our experiments point rather to the conclusion that the larger
      production of sugar after painting the unisolated pancreas is due to the fact
      that a large part of the adrenalin escapes to the peritoneum. The last mentioned
      view is supported by the statement of Herter and Wakeman that "applications to
      the kidney are apt to yield more sugar than similar application to the liver,
      intestine, spleen, or brain, but the glycosuria is less marked than after the
      pancreas has been painted." Emerson and one of us had shown that a dissolved
      substance painted upon a kidney with an intact membrane is incapable of
      penetrating the membrane and affecting the kidney, or even incapable of entering
      the circulation, except when the solution escapes to other parts of the
      peritoneum. It was this observation which led to the suggestion that the effects
      observed by Herter of painting the pancreas might have been due to the escape of
      adrenalin to the celiac ganglion. This point has not been directly tested, but
      several experiments were performed in which the adrenals were painted with the
      effect on sugar production apparently as intense as that obtained by painting the
      unisolated pancreas. However this may be, and whether the production of sugar
      after painting the unisolated pancreas is due to the escape of adrenalin to some
      definite organ covered by the peritoneum (celiac ganglion or adrenals) or whether
      the peritoneum as a whole is responsible for the sugar production, it appears
      that, when sugar production follows the intraperitoneal injection of adrenalin,
      it is not of pancreatic origin.

PMID- 19868233
TI  - THE SPIROCHETAL FLORA OF THE NORMAL MALE GENITALIA.
AB  - The varieties of spirochetes enumerated and photomicrographed from the male
      smegma flora represent practically every form hitherto described by Nankivell and
      Sundell and by Patterson in the specimens of urine from trench fever cases (Figs.
      32 and 33). The urethral flora, as studied by Stoddard, seem to contain more
      varieties, but, except those of his more detailed morphological descriptions,
      every form observed by him is among those found in the smegma. Stoddard saw
      certain forms with hooked ends suggestive of the Leptospira icterohaemorrhagiae
      of infectious jaundice, but the resemblance ends with this one feature, and
      differentiation should always be possible under the dark-field microscope, by
      means of which the leptospira reveals its highly characteristic minute elementary
      spirals, presenting the appearance of a chain of dots (Fig. 18). Fig. 19 shows
      that a very favorable fixation with the osmic acid vapor followed by Giemsa's
      staining may also bring out the elementary spirals. Of all the spirochetes, none
      has so closely set spirals as the jaundice leptospira, the distance between two
      spirals being only 0.5 micro. Various methods, including Fontana's, Benians', the
      mordant gentian violet stain, or Burri's India ink method, are inadequate to
      differentiate the leptospira from other spirochetes (Figs. 12, 14, 15, 16, 17).
      Why a positive spirochete finding with the films from the urethra and in the
      specimens of urine was not obtained, is difficult to explain, except on the
      grounds of the paucity of specimens examined. At all events, the recent negative
      results reported by Fiessinger with French soldiers and invalids after cleansing
      of the urethra and glans seem to be in harmony with my results. In conclusion it
      may be stated that Spironema refringens, Treponema calligyrum, and Treponema
      minutum represent practically all the spirochetal forms observed in the male
      smegma flora. A leptospira has never been conclusively shown to be present in the
      specimens of normal urine or smegma. For the satisfactory microscopic
      demonstration of a leptospira a dark-field illuminator is indispensable.

PMID- 19868234
TI  - PHYSIOLOGICAL STIMULATION OF THE CHOROID PLEXUS AND EXPERIMENTAL POLIOMYELITIS.
AB  - The experiments recorded in this paper serve, in the first place, to confirm the
      experiments of Dixon and Halliburton on the stimulating effect of intravenous
      injections of extracts of choroid plexus in the secretion of the cerebrospinal
      fluid, and extend their observations to monkeys. They bring out also the variable
      effects of the virus of poliomyelitis, variations affected by the quality of the
      virus and also by the individual powers of resistance to infection possessed by
      individual monkeys. These factors of variation must be taken into account in
      performing and interpreting experiments on infection and particularly those on
      immunity and specific therapy in relation to poliomyelitis. In general it may be
      said that experimental infection by way of the blood is not easy to produce in
      monkeys unless some contributing factor, such as the existence of a coincident
      aseptic meningitis, operates at the same time. And yet Experiments 1 and 2 show
      that when the strength of the virus is great the injection of relatively
      considerable quantities suffices to induce infection and paralysis, but not in
      all instances. The chief outcome of the experiments has been to determine the
      fact that when the intravenous inoculation of the virus does not in itself
      suffice to induce infection and paralysis, the intravenous injection of extracts
      of the choroid plexus, which in themselves excite the secretory functions which
      preside over the formation of the cerebrospinal fluid, is powerless to modify
      this result. This fact would seem to be of interest and importance, since it has
      already been shown that very slight structural changes in the meningeal-choroidal
      complex suffice to make possible or certain infection under these circumstances.
      Apparently mere augmentation, from time to time, of the secretory functions of
      the choroid plexus, through intravenous injection of an extract of the choroid
      plexus and while the virus is still circulating, is insufficient to insure
      passage of the virus from the blood into the nervous tissues, upon which
      infection depends. Neither does the augmentation exercise a restraining influence
      on the development of infection otherwise capable of taking place.

PMID- 19868235
TI  - THE AUTODIGESTION OF NORMAL SERUM THROUGH THE ACTION OF CERTAIN CHEMICAL AGENTS.
      I.
AB  - 1. By means of certain chemical reagents, normal guinea pig serum can be brought
      to autodigestion without the presence of any foreign substrate. There exists in
      normal sera a highly characteristic protease. 2. The serum ferment survives
      heating at 55 degrees C. for 30 minutes, but is completely inactivated at 60
      degrees C. for the same length of time. 3. The autodigestion of serum requires a
      temperature of about 37 degrees C., and no noticeable digestion takes place at a
      temperature of 16 degrees C. or lower. 4. Autodigestion of the serum may be
      brought about by chloroform and various saturated monovalent ketones and alcohols
      of the lower series. 5. The ketones and alcohols have a certain narrow limit of
      concentration for activating serum, beyond which the ferment is destroyed, even
      at room temperature. 6. The ketones and alcohols in concentrations regulated to
      activate serum at room temperature destroy the ferment when allowed to act on
      serum at 37 degrees C. for 30 minutes. The elimination of the concentrated
      reagents from serum by evaporation or dialysis protects the ferment from their
      destructive action. 7. A certain length of time is required for the chemical
      activators to complete their action. In this respect chloroform is much slower
      than acetone. 8. The chemical activators may be removed from the activated serum
      by means of vacuum, dialysis, or extraction with certain indifferent chemicals
      without causing a return of the serum to its original non-autolytic state. Once
      activated by these reagents, the serum remains in the activated state, in spite
      of the removal of the activators. 9. The ferment is highly sensitive to the
      reaction of the medium, being readily inactivated when the reaction exceeds a
      certain narrow limit towards acid or alkaline. The optimal digestion is obtained
      with a faintly alkaline or neutral reaction.

PMID- 19868236
TI  - THE AUTODIGESTION OF NORMAL SERUM THROUGH THE ACTION OF CERTAIN CHEMICAL AGENTS.
      II.
AB  - 1. The neutral fats, fatty acids, and lipoid bodies of serum seem to play no part
      in autodigestion. Neither the addition of fats or lipoids in excess to the serum,
      nor their removal by extraction with ether influences the phenomenon of
      autodigestion. 2. There is present in native serum an antienzymic substance which
      is closely related to the autolytic ferment of serum. 3. The antiseroprotease of
      normal serum has almost the same thermal resistance as the seroprotease; that is,
      it survives heating at 55 degrees C. for 30 minutes but is completely inactivated
      at 60 degrees C. for the same length of time. 4. The ferment can be removed from
      the serum by means of inorganic adsorbents, but the antienzymic substance remains
      in the treated serum. 5. The autolytic power of the sera of man and other animals
      is much weaker than that of guinea pig serum, but they contain as much as does
      the latter of the antisubstance which inhibits the digestion of the activated
      guinea pig serum. 6. The autodigestion of the activated serum is due to the
      splitting of the serum protein by the proteolytic ferment of the same serum and
      is brought about by the destruction of the antienzymic substance by the chemical
      reagents. On the other hand, the digestion products in a mixture of a foreign
      substrate and guinea pig serum are derived from the direct digestion of the
      substrate by the serum ferment. This digestion takes place in spite of the
      presence of the antiseroprotease. The serum separated from the substrate can no
      longer produce a split product, but is as actively antienzymic as the original
      serum and undergoes autodigestion only when treated with acetone or other
      chemical activators.

PMID- 19868237
TI  - ANTIBODY PRODUCTION AFTER PARTIAL ADRENALECTOMY IN GUINEA PIGS.
AB  - By careful aseptic operation it was found possible to remove approximately three
      quarters to seven-eighths of the adrenal tissue of guinea pigs without causing
      symptoms of adrenal insufficiency. Guinea pigs were immunized to Bacillus
      typhosus or to hen corpuscles at varying intervals before or after the operation,
      and the curves of antibody formation traced for 2 to 3 months after immunization.
      Comparisons with the antibody curves of control animals similarly immunized fail
      to show that the adrenalectomy had any influence upon the rise or persistence of
      antibodies in the blood. For the purposes of the study it was not deemed
      necessary to produce an acute adrenal insufficiency. If the adrenal glands were
      the site of antibody formation or played an essential part in immunity processes,
      it does not seem probable that the small remainder of adrenal tissue left in situ
      to sustain life would affect quantitatively the antibody response to a given
      antigen injection as do the entire normal glands. We therefore interpret the
      experiments to indicate that not only are the adrenal glands not one of the
      important sources of typhoid agglutinins, or of hemagglutinins or hemolysins, but
      they play no essential part in the mechanism by which these antibodies are
      produced and maintained in the body.

PMID- 19868238
TI  - AESTIVO-AUTUMNAL MALARIA. THE EXTRACELLULAR RELATION OF THE CRESCENTIC BODIES TO
      THE RED CORPUSCLE AND THEIR METHOD OF SECURING ATTACHMENT.
AB  - AEstivo-autumnal parasites, including the crescentic bodies, are always
      extracellular; that is, they are attached to the external surface of the red
      corpuscles. Crescentic bodies attach themselves to the red corpuscles just as the
      younger parasites do, by encircling, with their cytoplasm, mounds of hemoglobin
      substance. These hemoglobin mounds may be seen protruding through various
      portions of the crescentic bodies, as well as at the periphery of the parasites.
      The base of the mounds is occasionally outlined by the chromatin or pigment
      granules. The hemoglobin mounds protruding through the body proper of the
      crescentic bodies do not seem to alter the general outline of the parasites. The
      outline of the parasites may be traced through the transparent mounds. Whenever
      attaching pseudopodia are observed they are seen to arise from the cytoplasm of
      the parasites and may be in the form of loops or strings. When the crescents are
      attached they proceed to dissolve the hemoglobin to make it available for
      utilization, assimilating what is required for nutrition, the waste product being
      in the form of pigment granules. After the hemoglobin mounds, to which the
      crescents are attached, have been decolorized by parasitic action, an appearance
      is obtained which has been described by most observers as vacuolization of the
      crescentic body. These observers believe the picture to be one of degeneration.
      The decolorized mounds or vacuoles ("achromatic areas") seen in connection with
      malarial parasites correspond to the nutrition vacuoles of the common amebae, and
      possibly the malarial parasite may, like these amebae, secrete reserve food.

PMID- 19868239
TI  - AESTIVO-AUTUMNAL PARASITES. MULTIPLE INFECTION OF RED CORPUSCLES AND THE VARIOUS
      HYPOTHESES CONCERNING IT.
AB  - 1. Multiple infection of red corpuscles with young parasites is seen in all
      malarial infections, but it is found most frequently in the aestivo-autumnal
      infections. The occurrence is accidental and has no significance other than that
      if the instances are numerous it suggests a heavy infection. 2. In instances of
      multiple infection the young parasites may be seen to be attached: (a) each
      encircling its own corpuscular mound, giving the typical ring-form picture, or
      (b) two or more encircling one corpuscular mound, giving the appearance of a
      single ring with two or more masses of chromatin. 3. Certain hypotheses as to the
      conjugation of malarial parasites have been formulated by observers to explain
      various instances of multiple infection. I do not believe that conjugation ever
      occurs. I believe that these hypotheses resulted from observation of certain
      appearances presented by the attached parasites, as when they are attached so
      closely together that they may appear to be adherent, or when two or more are
      attached to one corpuscular mound, giving the appearance of a single parasite
      with more than one mass of chromatin. 4. Certain appearances have also been
      described as a precocious division of the chromatin masses of young parasites. In
      these instances the chromatin granules were usually described as varying in size.
      Such an appearance may be explained as follows: (a) two young parasites in
      varying stages of development may encircle one corpuscular mound, the cytoplasm
      of one parasite being superimposed over that of the other parasite, giving a
      picture of a single ring with two unequal masses of chromatin; or (b) the
      variation in the size and number of the chromatin masses may be the result of
      traumatism, as the nuclei of young parasites are rather easily broken up. 5.
      Multiple infection of red corpuscles with crescentic bodies is considered rather
      a rare occurrence. It is always accidental, and if the instances are numerous it
      means a severe infection. 6. When one accepts the fact that all malarial
      parasites are attached to the external surface of the red corpuscles, the
      biological and morphological characteristics of the parasites cease to be
      obscure.

PMID- 19868240
TI  - THE LYMPHOCYTE IN NATURAL AND INDUCED RESISTANCE TO TRANSPLANTED CANCER : III.
      THE EFFECT OF X-RAYS ON ARTIFICIALLY INDUCED IMMUNITY.
AB  - Mice artificially immunized against a transplantable carcinoma, inoculated, and
      proved immune, may be again rendered susceptible to the same tumor by exposure to
      the x-rays. The immune animals which have not been treated with the x-rays
      preserve, to a large degree, their resistance to a second inoculation of the
      tumor in question.

PMID- 19868241
TI  - THE PASSAGE OF NEUTRALIZING SUBSTANCE FROM THE BLOOD INTO THE CEREBROSPINAL FLUID
      IN ACTIVELY IMMUNIZED MONKEYS.
AB  - For the neutralization of the virus of poliomyelitis by antibodies, active
      complement is not required. In carrying out immunity tests it is imperative to
      choose a virus of established grade of virulence and to make adequate control
      observations. The neutralizing substances pass from the blood of actively immune
      monkeys into the cerebrospinal fluid when the permeability of the meningeal
      choroidal complex is increased by an aseptic inflammation such as that induced by
      an intraspinal injection of horse serum. The immunity bodies in effective
      neutralizing quantities can be detected in the cerebrospinal fluid as early as 12
      hours and as late as 48 hours after the intraspinal injection of horse serum.
      Doubtless the passage continues as long as the inflammation persists. This
      ability of the neutralizing substances to pass from the blood into the
      cerebrospinal fluid under conditions of inflammation doubtless plays an important
      part in arresting the multiplication of the virus on which the cessation and
      restoration of the poliomyelitic processes depend. The widespread involvement in
      the inflammatory conditions of the meninges, choroid plexus, and substance of the
      nervous organs, accompanied by severe lesions of the blood vessels in the last
      structures especially, opens the way widely for the passage of antibodies into
      the cerebrospinal fluid, whence all parts of the nervous tissues are reached, and
      also, probably, for direct transudation into the affected parts of the spinal
      cord and brain. The neutralization of the virus on which the continuance of the
      active pathological process depends is thus readily accomplished. Under these
      circumstances the use of an alien specific immune serum to anticipate the action
      of the individual's own immunity products appears logical, while the employment
      of normal serum has no basis in experiment and would seem not to offer any
      therapeutic advantage whatever.

PMID- 19868242
TI  - RESULTS OF PROPHYLACTIC INOCULATION AGAINST PNEUMOCOCCUS IN 12,519 MEN.
AB  - 1. From a study of the agglutinins and protective power of the serum of 42
      persons vaccinated against the pneumococcus, Types I, II, and III, it is
      demonstrated that a definite immune response has been secured to Types I and II
      by the dose of vaccine employed. Little evidence of response to Type III can be
      demonstrated by these methods, but this is of less significance in that in
      animals it is relatively difficult to secure antibodies against this strain in
      the serum, even though a considerable degree of active immunity may have been
      produced in the vaccinated animal. 2. The degree of response to the vaccination
      appears to be dependent upon the total dosage of each type of pneumococcus
      administered. While some response may be elicited by 2(1/2) billion cocci of each
      type, a much more constant and greater response follows 13 billion. 3. In
      subcutaneous administration the manner in which the total dosage is divided,
      whether given in a single large dose, in seven small daily doses, or in three to
      five moderate doses at 3 to 7 day intervals, seems to have little influence upon
      the degree of immune response, provided the total dosage is the same. 4. The
      local and general toxic reaction varies greatly in different individuals. The
      smaller the individual doses, the fewer are the severe reactions. This makes it
      desirable to divide the total dosage into as many inoculations as circumstances
      make practicable. 5. At Camp Upton 12,519 men have been vaccinated against
      Pneumococcus Types I, II, and III. Three or four doses were given at intervals of
      5 to 7 days with a total dosage of 6 to 9 billion of Types I and II and 4(1/2) to
      6 billion of Type III. 6. During the 10 weeks that have elapsed since the
      vaccination, no cases of pneumonia of these three types have occurred among the
      men who had received two or more injections of vaccine. 7. In a control of
      approximately 20,000 men there were twenty-six cases of Pneumococcus Types I, II,
      and III pneumonias during the same period. 8. The incidence of Pneumococcus Type
      IV pneumonia and streptococcus pneumonia was much less among the vaccinated
      troops than among the unvaccinated. No explanation has been advanced for this
      difference. 9. Small sterile infiltrations disappearing spontaneously
      occasionally follow the injection of large doses of pneumococcus vaccine and
      appear to be an expression of cutaneous hypersusceptibility. 10. The persons who
      develop these lesions exhibit local reactions to each dose of vaccine. They also
      give abnormally marked reactions to intradermal injections of pneumotoxin. They
      do not, however, exhibit anything notable in the agglutinative or protective
      powers of their sera after vaccination. Whereas the immune response is
      characteristically specific for the type of pneumococcus, this reaction is not
      specific for any type. We have found no evidence that Type III is more prone to
      elicit these severe local reactions than are Types I and II. 11. Prophylactic
      vaccination against pneumococcus of Types I, II, and III is practical and
      apparently gives protection against pneumonia produced by these types. It remains
      to be determined how long this immunity persists.

PMID- 19868243
TI  - A HOMOHEMOLYTIC SYSTEM FOR THE SERUM DIAGNOSIS OF SYPHILIS.
AB  - The elimination of the foreign complement and corpuscles from the test for the
      serodiagnosis of syphilis has been attempted, and the results so far obtained are
      very satisfactory. Instead of using guinea pig complement, fresh human serum was
      utilized for the source of complement for the production of hemolysis upon the
      human corpuscles in the presence of an adequate amount of the specific anti-human
      amboceptor (prepared in rabbits). Usually 0.1 cc. of fresh human serum contains
      enough complement to hemolyze 1 cc. of a 1 per cent suspension of human
      corpuscles, but the amount of anti-human amboceptor required in this combination
      is about five to seven times that necessary when guinea pig complement (0.04 cc.)
      is used. It has also been shown that when a given human serum contains
      insufficient complement, an adequate quantity (0.1 cc. is usually enough) of
      another fresh negative serum may be added to supplement it. However, one rarely
      encounters this group of sera. Inactivated human sera can also be examined by
      utilizing human complement from another source (the serum must be fresh, active,
      and negative). The only drawback to the present method is the comparatively large
      amount of anti-human hemolytic amboceptor required. It is estimated that 30 to 40
      cc. of the anti-human hemolytic immune serum, from one rabbit, of high potency
      say 0.005 cc.-would be enough to examine about 3,000 to 4,000 cases (0.01 cc. for
      each case), whereas if guinea pig complement were used the same amount would
      cover about 15,000 tests (0.002 cc. for each case). In a large hospital or in the
      Army there should be no difficulty in preparing any amount of the anti-human
      hemolytic amboceptor. For example, material for 100,000 tests could be prepared
      within 1 month in less than 100 rabbits. The amboceptor serum can be used in the
      fluid state, or, if the titer is high, impregnated into filter papers. Special
      attention should be called to the fact that to obtain a powerful anti-human
      hemolytic amboceptor five to six intraperitoneal injections of corpuscles,
      thoroughly washed (until there is no trace of serum in the supernatant fluid), in
      doses of 5, 7, 10, 10, 10, and possibly another 10 cc. of the concentrated
      suspension (restored to the. original volume of the blood) are required. The
      bleeding may be done by the 9th or 10th day. The animals may be kept after
      bleeding for the production of more amboceptor by subsequent injections of the
      washed corpuscles. Finally, it should be emphasized that only the acetone
      insoluble fraction of tissue lipoids of required standards (Noguchi) should be
      used when utilizing the human complement in the fixation test.

PMID- 19868244
TI  - AN EXPERIMENTAL STUDY OF VACCINATION AGAINST BACILLI DYSENTERIAE.
AB  - The purpose of the present investigation was to determine a practical method of
      vaccination against bacillary dysentery. It has been emphasized that the toxicity
      of the dysentery group of organisms, especially that of the Shiga bacillus, is
      such as not to permit of their employment in simple saline or aqueous
      suspensions. If, on the other hand, their toxicity is removed by the addition of
      certain chemicals, the antigen of the bacilli is so changed as not to be suitable
      for immunization purposes. The toxicity of the bacilli can also be diminished by
      the addition of immune serum. There is no essential difference in the result
      whether unmodified serum is used or that modified by Gibson's method. The use of
      serum with vaccines cannot be recommended, in spite of the relative non-toxicity
      of such mixtures. The specific immunity response is reduced, while the parenteral
      injection of horse serum in large groups of men is objectionable because of the
      serum sensitization which it produces. It has been shown that a certain vegetable
      oil, almond oil, (and this statement may apply to a number of non-irritating,
      absorbable oils) is capable of overcoming many of these disadvantages. The oil
      acts as a passive agent in merely suspending the bacteria without altering their
      properties. The slow absorption of the suspended bacteria from this vehicle
      mitigates the toxic effects of the dysentery bacilli. At the same time it does
      not interfere with the immunity response-antibacterial and antitoxic. If the
      absorption is too slow, however, as in the instances in which lanolin was added,
      less satisfactory results follow. The proper rate of absorption is as important a
      factor as the proper vegetable oil. The latter condition has been emphasized in
      the consideration of the effects of an objectionable olive oil. The
      neutralization of the oil should be complete. F. G. S. and J. W. S. suffered from
      severe local reactions, the results of the local deposition of soaps, which are
      difficult of absorption. As a result of the slow absorption of the dysentery
      bacilli from the oily suspension only slight local and general reactions follow,
      and it is possible to give at one time and in a single dose a sufficient number
      of the killed dysentery bacilli to incite a high degree of immunity. The precise
      series of events following the injection of the oily vaccine are: During the 1st
      day, an erythematous area develops at the site of injection, which is not
      especially painful. There may be a slight systemic reaction, consisting in
      headache and slight chilliness. After 24, sometimes after 48 hours, an induration
      appears at the site of injection, varying from 2 to 4 cm. in diameter, which
      remains unchanged for a few days, then begins to recede, complete absorption
      requiring from 1 to 3 weeks. The induration remains localized and has no tendency
      to break down. It causes no inconvenience. During the period of absorption the
      organism of the host continually receives antigen. The rule of immunology is that
      while antigen is circulating the antibodies are usually not demonstrable; it is
      only after all the antigen disappears that the antibodies appear in greatest
      concentration. Since the vaccine is slowly absorbed, the reasons for the delayed
      appearance of antibodies, as well as their persistence, become obvious.

PMID- 19868245
TI  - COCCIDIOSIS IN YOUNG CALVES.
AB  - Discharges of blood per rectum, associated with oocysts of coccidia, were
      observed occurring in young calves during the warmer season of the year. In a
      small percentage of the cases death was probably due directly to the coccidiosis.
      Although the disease, known as red dysentery in Switzerland, may have existed in
      this country for some time, there seems to have been no knowledge of its
      existence and no reports of it have thus far been published. The coccidia have
      been artificially cultivated and shown to produce four spores. Two oocysts of
      quite different dimensions and having minor differential characters were
      encountered in the same animal in several instances. The invasion of the
      epithelium of the small intestine was slight. The chief seat of the parasitism
      was the large intestine. The lesions following the loss of epithelium were
      superficial hemorrhages and filling up of the denuded tubules with
      polymorphonuclear leukocytes.

PMID- 19868246
TI  - EXPERIMENTAL TRYPANOSOMIASIS: ITS APPLICATION IN CHEMOTHERAPEUTIC INVESTIGATIONS.

PMID- 19868247
TI  - STUDIES IN BOVINE MASTITIS : I. NON-HEMOLYTIC STREPTOCOCCI IN INFLAMMATION OF THE
      UDDER.
AB  - It seems clearly established that non-hemolytic streptococci are responsible for
      a considerable number of cases of bovine mastitis. Of the 81 animals examined, 31
      were suffering from infections of this type. The lesions produced in invaded
      quarters varied from an involvement of only the lining epithelium of the large
      milk ducts to severe degeneration and necrosis of the secreting epithelium. In
      one instance a considerable portion of the glandular elements had been replaced
      with connective tissue. The streptococci fall into two groups when their action
      on the various carbohydrates is considered. Thirty-four strains fermented
      dextrose, lactose, saccharose, maltose, and salicin; five others attacked the
      first four sugars but failed to produce acid in salicin. All mastitis
      streptococci failed to act upon raffinose, inulin, or mannite. One species
      isolated from a mammary abscess produced acid in all the carbohydrates. All the
      strains were agglutinated with an antiserum prepared from one typical strain. The
      agglutination titer varied over wide limits, although all the streptococci were
      agglutinated at a dilution of 1:500. None of the strains inoculated proved
      pathogenic for rabbits. A pig fed on the milk from two typical cases of mastitis
      remained well.

PMID- 19868248
TI  - THE CLASSIFICATION OF HEMOLYTIC STREPTOCOCCI.
AB  - 1. The hemolytic variety of streptococcus is homogeneous, consisting of members
      that are nearly identical. 2. This homogeneity is most strikingly displayed in
      the behavior of these streptococci in the complement fixation reaction, all the
      strains studied reacting in a nearly identical way with all the antisera.

PMID- 19868249
TI  - THE RELATION BETWEEN HEMOLYTIC AND NON-HEMOLYTIC STREPTOCOCCI, AND ITS POSSIBLE
      SIGNIFICANCE.
AB  - 1. The relation between hemolytic and non-hemolytic streptococci is orderly and
      arises from the fact that the former variety is unique while the latter is
      heterogeneous. 2. Analogous considerations of the classification, distribution,
      and pathogenicity of the streptococcus group and the pneumococcus and colon
      typhoid groups show a definite parallelism. 3. These considerations suggest that
      unique varieties of bacteria associated with man are the more highly invasive,
      while the heterogeneous varieties are more saprophytic.

PMID- 19868250
TI  - RENAL FUNCTION IN EXPERIMENTAL HYDRONEPHROSIS.
AB  - Complete obstruction of the ureter causes atrophy of the renal parenchyma,
      especially marked in the portions lateral to the renal sinus. The longer the
      duration of the obstruction, the greater is the degree of atrophy. If the
      obstruction is removed within 2 weeks the kidney may regain its normal structure
      except for a varying amount of atrophy in the lateral portions. Kidneys
      obstructed for 2 weeks or less may regain their normal function, as measured by
      the phthalein test. The longer the period of obstruction, the slower is the rate
      of recovery. A hydronephrosis of 7 days' duration required 40 days, and one of 14
      days' duration required 152 days to recover normal function.

PMID- 19868251
TI  - PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : III. TOXIC PROTEIN CATABOLISM
      AND ITS INFLUENCE UPON THE NON-PROTEIN NITROGEN PARTITION OF THE BLOOD.
AB  - The acute intoxication following an injection of a toxic proteose is usually
      associated with a large increase (40 per cent or more) in the non-protein
      nitrogen of the blood. This increase is found chiefly in the blood urea nitrogen,
      but the amino and peptide nitrogens also may show small increases. The changes
      observed in the blood non-protein nitrogen are identical with those which follow
      the feeding of large amounts of meat (8). These facts indicate that the proteose
      intoxication causes an abnormally rapid autodigestion of tissue proteins, but
      that the nitrogenous end-products are, in chief part at least, the same that
      result from normal catabolism of food proteins. There is no evidence that the
      autolytic products play any part in causing the intoxication. The possibility of
      such a part and a resultant vicious circle is not excluded, but from the
      available facts the autolysis appears more as a result rather than cause of the
      intoxication. It appears possible that in disease or intoxication tissue
      catabolism may be enormously accelerated and yet yield the end-products of normal
      protein metabolism.

PMID- 19868252
TI  - PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : IV. THE METABOLISM OF DOGS
      WITH STERILE ABSCESS, PANCREATITIS, AND PLEURITIS.
AB  - Sterile abscess, pleuritis, and pancreatitis give a clinical reaction in the
      experimental animal very like the same acute inflammatory processes due to
      bacterial activity, provided the bacterial agents are limited to the initial
      location. The curve of urinary nitrogen excretion in the fasting dog shows the
      same precipitous and sustained rise in sterile and bacterial inflammatory
      reactions. This indicates that the same type of protein injury and autolysis in
      the body is produced by the sterile inflammatory reaction as by the bacterial
      reaction. It is assumed that the primary effect of the chemical agent or of the
      bacterial growth in the tissues is local cell injury or necrosis. This injured
      cell protoplasm undergoes prompt autolysis with escape of toxic protein split
      products. These toxic protein split products may be, in part at least, of the
      proteose group and are absorbed into the circulation, producing the familiar
      general reaction. The injury of body protein is obvious from the great increase
      in elimination of nitrogen in the urine and appears to be the same in sterile and
      in bacterial inflammation. The injurious agent in the sterile inflammation must
      be derived from the host protein, and we may assume with safety that much of the
      injurious material emanating from a septic inflammation must come from the host
      protein rather than from the bacteria. Acute sterile pancreatitis is one of the
      purest examples of an acute non-specific reaction where the intensity of the
      host's intoxication may reach a maximum in 12 to 24 hours. We believe that
      fundamentally this reaction is very similar to that observed after the production
      of a sterile abscess or pleurisy. Non-specific intoxication must account for the
      sterile reactions described above. Septic inflammations show the same acute
      reaction and injury of body protein. The deduction is obvious-that a great part,
      at least, of the reaction in septic inflammation is truly non-specific and
      results from the primary injury of the host's protein and cell autolysis.

PMID- 19868253
TI  - PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : V. THE INCREASE IN NON
      PROTEIN NITROGEN OF THE BLOOD IN ACUTE INFLAMMATORY PROCESSES AND ACUTE
      INTOXICATIONS.
AB  - Sterile abscess formation in the dog is accompanied by a large increase in output
      of urinary nitrogen and also by a small but definite increase in the blood non
      protein nitrogen. All this nitrogenous material of course is derived from body
      protein injury and autolysis. Septic inflammation in the dog (pleurisy,
      pneumonia, peritonitis, etc.) likewise shows a distinct rise in the blood non
      protein nitrogen. This rise is not often so great as that frequently observed in
      the intoxication of intestinal obstruction. Many acute infections in man
      (septicemia, peritonitis, pneumonia, etc.) show a definite rise in the non
      protein nitrogen and urea nitrogen of the blood; some cases show a very great
      rise above normal (over 100 mg. of non-protein nitrogen per 100 cc. of blood).
      There may be no anatomical change in the kidney beyond the familiar picture of
      cloudy swelling. This does not exclude the possibility of some transient
      functional derangement of the kidney epithelium. Certain obscure intoxications in
      man may show a considerable rise in the non-protein nitrogen of the blood,
      indicating a large amount of protein disintegration. These findings must be taken
      into account in any clinical analysis and interpretation of high non-protein
      nitrogen of the blood in pathological conditions.

PMID- 19868254
TI  - STUDIES IN BOVINE MASTITIS : II. THE RELATION OF HEMOLYTIC STREPTOCOCCI TO UDDER
      INFECTIONS.
AB  - Hemolytic streptococci produce more or less severe inflammations of the udders of
      cows. Frequently infected quarters are swollen, firm, hot, and tender. In a
      number of instances it has not been possible to detect gross changes in the
      mammary gland. The streptococci isolated from the invaded quarters have produced
      clear zones of hemolysis immediately surrounding the colonies when cultivated in
      horse blood agar plate cultures. The hemolytic zone has varied from a clear,
      narrow band up to zones 1.7 to 2 mm. wide. When the streptococci are classified
      according to their action upon carbohydrates, they fall into two broad groups:
      the larger consists of nineteen strains fermenting dextrose, lactose, saccharose,
      maltose, and salicin; and a smaller number comprising ten species produces acid
      in dextrose, lactose, saccharose, and maltose and fails to ferment salicin. One
      of the non-salicin-fermenting strains did not attack saccharose. In no instance
      was acid production noted in raffinose, inulin, or mannite. All streptococci
      except three were agglutinated by an antiserum obtained from a rabbit immunized
      with a single strain. Freshly isolated cultures when injected intravenously into
      rabbits possess but slight pathogenicity. Localizations in the joints occurred in
      two instances. The others either failed to affect the general condition of the
      animals or produced only a slight febrile reaction.

PMID- 19868255
TI  - THE ETIOLOGY OF EPIDEMIC POLIOMYELITIS.
AB  - Streptococci have been isolated from the central nervous system of monkeys dead
      of poliomyelitis. Streptococci have also been isolated from the central nervous
      system of monkeys dead of other causes as well as from the brains of normal
      rabbits. Streptococci isolated from poliomyelitic monkeys do not differ from
      those isolated from monkeys and rabbits dead from other causes. An etiological
      relation has not been established between streptococci and poliomyelitis. We have
      at several times isolated an organism that was similar to the globoid bodies
      culturally, morphologically, and in staining reaction, but have not been able to
      carry it along for more than three generations. The pathogenicity of these
      organisms has therefore not been tested on monkeys. We have not been able to
      produce typical lesions of poliomyelitis in rabbits by the injection of either
      the poliomyelitic virus or streptococci.

PMID- 19868256
TI  - A NOTE ON THE PRODUCTION OF ACID BY PNEUMOCOCCI.
AB  - 1. Actively growing pneumococci produce acid at such a rate that change in the pH
      of the medium parallels change in rate of growth. 2. The death of the pneumococci
      is not followed by change in the reaction. 3. Acidification during growth in beef
      infusion media proceeds until a pH of about 7 is reached. At this point growth
      stops. The increase in hydrogen ion concentration is not the only origin of the
      injury to the cell that causes lag in a subsequent culture. 4. The increase in
      hydrogen ion concentration of the medium is not the sole cause of cessation of
      growth.

PMID- 19868257
TI  - INFLUENCE OF TEMPERATURE UPON THE VELOCITY OF THE COMPLEMENT FIXATION REACTION IN
      SYPHILIS.
AB  - Examination of syphilitic serum or cerebrospinal fluid can be made at any
      temperature between 23 degrees and 37 degrees C. The velocity of the fixation
      reaction, including the fixation of complement and subsequent hemolysis, is
      greater at a higher temperature, the optimum point being 37 degrees C. The
      maximum reaction is also reached, however, when the mixture of lipoids,
      syphilitic serum, and complement is allowed to stand for a long enough period at
      a lower temperature, the minimum thermal point being near 23 degrees C. For the
      optimum temperature (37 degrees C.) an incubation of 30 minutes is sufficient,
      while for the minimum temperature (23 degrees C.) 2 hours are necessary. At the
      temperature of 30 degrees C. the reaction proceeds with moderate velocity and is
      complete within 60 minutes. Guinea pig complement gave a sharper reaction with
      the sera which contained less than one unit of the fixing substance. Fixation is
      complete, however, at any of the three temperatures within 20 minutes when there
      are more than two units present. A serum containing one unit of fixing substance
      will complete reaction within 30 minutes at 37 degrees C., 60 minutes at 30
      degrees C., and 2 hours at 23 degrees C., irrespective of whether human or guinea
      pig complement is used. For many reasons a properly adjusted thermostat for 37
      degrees C. is recommended for conducting the serum diagnosis of syphilis when
      possible, but it should not be overlooked that at a temperature near 30 degrees
      C. an entirely reliable result can be obtained without a special incubator. Even
      at a temperature as low as 23 degrees C. the test can be carried out if
      sufficient length of time is allowed. The foregoing conclusions refer only to the
      systems in which the acetone-insoluble fraction of tissue lipoids is used as
      antigen.

PMID- 19868258
TI  - RESTORATIVE EFFECT OF SALTS OF MAGNESIUM AND CALCIUM AFTER LETHAL DOSES OF SODIUM
      OXALATE.
AB  - The experiments presented in this paper brought out the following facts.
      Intramuscular injections of sodium oxalate into rabbits in doses of 0.18 and 0.2
      gm. proved to be invariably fatal, death generally occurring in a comparatively
      short time. The symptoms consisted in excitation and tonic and clonic convulsions
      of diminishing strength if death was delayed. Some animals succumbed in the first
      convulsion. From the experiments in which magnesium or calcium was added, it was
      evident that massage of the site of the oxalate injection is unmistakably an
      aggravating factor. In the experiments with the addition of magnesium or calcium,
      doses of 0.2 gm. of oxalate were used, with or without massage. The character of
      the effect which follows an addition of magnesium and calcium was studied in
      animals which received oxalate in doses above the minimal lethal one.
      Nevertheless, there was practically in all cases clear evidence that the effect
      of the additional injections was in the nature of an antagonism to the oxalate
      effects. An injection of 0.6 gm. of magnesium not only alleviated or abolished
      the excitation and convulsions, characteristic of oxalate poisoning, but also
      reduced the mortality by 30 per cent. When the dose of magnesium was only 0.4 gm.
      per kilo of body weight and the site of the injection of the oxalate was not
      massaged-a condition in which 0.2 gm. of oxalate alone was invariably fatal-the
      mortality was reduced by 80 per cent. The favorable effect of injections of
      calcium chloride depended upon the quantity injected and the length of the
      interval elapsing between the injection of the oxalate and that of the calcium.
      When the site of the oxalate was massaged and only 5 cc. of the calcium solution
      were injected, the animals succumbed to the oxalate poisoning. When 10 cc. of
      calcium were given 1 minute after the oxalate injection, the animals survived.
      When the site of the oxalate injection was not massaged, then even 5 cc. of the
      calcium were sufficient to save life. A curative effect of calcium upon oxalate
      poisoning has been claimed by previous writers. This is not difficult to explain
      and probably consists in the simple chemical process which can be demonstrated in
      vitro. Oxalates precipitate calcium salts in vitro and have the same effect
      within the animal body. By virtue of this precipitation the calcium of the body
      is reduced below the amount indispensable to maintain life. Loeb said: "It is due
      to the presence of Ca- (and K-) ions in our blood that our muscles do not
      contract rhythmically." The convulsive movements in oxalate poisoning may be due
      at least partly to a reduction of the calcium content of the fluids of the animal
      body. In our experiments it required an injection of 10 cc. of calcium chloride
      to restore the calcium content to the indispensable amounts; the injection of 5
      cc. was effective only when the site of the oxalate injection was not massaged.
      The fact that calcium salts are antagonistic to the effects of magnesium salts,
      which are practically only inhibitory in their nature, does not exclude the
      possibility that under certain conditions calcium may also exert an inhibitory
      effect. The following is an instructive illustration. Prolonged perfusion of a
      nerve muscle preparation with sodium chloride abolishes the irritability of the
      motor nerve endings; addition of calcium chloride restores it. On the other hand,
      perfusion with calcium chloride alone promptly abolishes this irritability. In
      one case it restores the irritability while in the other it inhibits it. It is
      different with regard to the action of magnesium upon oxalate poisoning.
      Superficially it seems that there is a direct contradiction between the results
      reported in a previous communication; and the experiments reported in this paper.
      The first series of experiments demonstrates that oxalate and magnesium act
      synergetically, while in the present series evidence is brought forward that
      magnesium acts antagonistically to the poisonous effects of the oxalate. However,
      this seeming contradiction may be explained on the assumption that oxalates,
      especially in larger doses, aside from their calcium-precipitating property,
      exert by means of a yet unknown factor a further toxic effect which favors the
      development of excitation and convulsions, which in turn lead to exhaustion and
      death. The employment of carefully selected doses of a magnesium salt will reduce
      or abolish the excitation and spastic attacks and thus will prevent exhaustion
      and hence save life. We may thus say that the favorable antagonistic action of
      magnesium against large, fatal doses of an oxalate is merely symptomatic in its
      nature-similar, for instance, to the favorable effect of chloroform upon
      strychnine, convulsions-while the synergetic action of subminimal doses of
      magnesium and oxalate may be considered as specific in nature. The precipitating
      action of the oxalate decreases the calcium content and thus increases the
      effectiveness of the inhibitory action of the subminimal dose of magnesium.

PMID- 19868259
TI  - STUDIES OF UROBILIN ELIMINATION IN THE NORMAL AND ANEMIC DOG.
AB  - 1. The output of urobilin is increased in experimental trypanosome anemia
      presumably as a result of the increased blood destruction. 2. The administration
      of salvarsan (arsenobenzol) during the anemic period, if it checks the blood
      destruction, reduces the urobilin elimination, but this result does not follow
      unless the blood picture improves. 3. Following splenectomy in the normal dog an
      increase in the urobilin elimination of varying degree occurs, the significance
      of which is doubtful. 4. Splenectomy during the period of anemia does not cause a
      decrease in urobilin elimination. The experiments support the view that the
      elimination of urobilin may be considered as an index of blood destruction, but
      they do not explain the decrease in the elimination occurring in man in certain
      forms of hemolytic anemia following splenectomy.

PMID- 19868260
TI  - MODIFICATIONS OF CULTURE MEDIA USED IN THE ISOLATION AND DIFFERENTIATION OF
      TYPHOID, DYSENTERY, AND ALLIED BACILLI.
AB  - The three media as modified-Endo medium, neutral red-brilliant green, and the
      lead acetate Russell double sugar-have proved in our hands the best combination
      for the isolation and rapid differentiation of the various organisms belonging to
      the typhoid-dysentery group of bacilli.

PMID- 19868261
TI  - AN EXPERIMENTAL TEST OF NUZUM'S ANTIPOLIOMYELITIC SERUM.
AB  - The antistreptococcic serum of Nuzum and Willy has failed to show in the monkey
      neutralizing or therapeutic power when applied by their methods against small
      doses of the virus of poliomyelitis. Under the same conditions the serum of
      monkeys recovered from experimental poliomyelitis proved neutralizing and
      protective. The experimental and other evidence adduced by those who regard the
      streptococcus as playing an essential part in the pathology of epidemic
      poliomyelitis and the antistreptococcic sera as exhibiting therapeutic properties
      for man and monkeys is regarded as imperfect and inconclusive.

PMID- 19868262
TI  - A PLEOMORPHIC BACILLUS FROM PNEUMONIC LUNGS OF CALVES SIMULATING ACTINOMYCES.
AB  - A bacillus was found associated in pure culture with an extensive lobar
      bronchopneumonia in calves. It occurs in the exudate as a minute bacillus in
      small groups. In cultures it appears in three forms: as a bacillus, as a coccus
      like endospore or arthrospore, and as a conglomerate Actinomyces-like flake or
      colony with peripheral clubs. The bacillar and coccoid forms occur on agar, the
      Actinomyces form in the condensation water of coagulated serum (horse). The
      coccoid form is probably a spore state, the minute refringent spore being
      contained in a roundish, unstainable mass representing either the remnants of
      bacillar substance or some capsular material. The somewhat striking similarities
      between this organism and Actinomyces are expressed by the massed growth with
      terminal clubs, the bacillar and coccoid stages, all of which are characteristic
      of Actinomyces. Sealing the tubes is essential for multiplication. Cultures must
      be renewed within a few days, otherwise multiplication fails. The substance which
      forms the bulk of the radiate flocculi is probably of capsular nature, greatly
      overproduced in serum tubes and scarce or absent on agar. Its nature is unknown.
      The organism is not appreciably pathogenic when injected into certain small
      laboratory animals.

PMID- 19868263
TI  - THE OPTIMUM HYDROGEN ION CONCENTRATION FOR THE GROWTH OF PNEUMOCOCCUS.
AB  - 1. The optimum hydrogen ion concentration for the growth of the various types of
      pneumococcus is a pH of about 7.8. 2. The limiting hydrogen ion concentrations
      for the growth of pneumococcus are a pH of 7.0 and a pH of 8.3. 3. Phosphates
      used in adjusting reactions of media retard growth if present in a concentration
      greater than 0.1 molecular. 4. Culture media for pneumococci should, therefore,
      have an initial reaction between a pH of 7.8 and 8.0 and a total salt
      concentration not exceeding 0.1 M.

PMID- 19868264
TI  - DETERMINATION OF THE QUANTITY OF SECRETING TISSUE IN THE LIVING KIDNEY.
AB  - 1. Under the strain induced by the administration of urea, it is possible to
      demonstrate the relation between the degree of anatomical damage in the kidney
      and the degree of defect in the urea-excreting capacity induced by uranium. 2.
      The closest correlation between structure and function was obtained when the
      ratio between the urea content of the urine and of the blood was used as the
      measure of function.

PMID- 19868265
TI  - A FURTHER STUDY OF EXPERIMENTAL PAROTITIS.
AB  - A new series of inoculations into cats of the filtered sterile salivary
      secretions derived from cases of parotitis has been described. They confirm the
      observations made in 1915-1916 and extend them to include the epidemic parotitis
      occurring in our military forces. Incidentally confirmatory evidence of the
      filterable nature of the causative agent of mumps has been obtained. It has been
      determined that the saliva of man and of inoculated cats, and the inoculated
      glands of the latter animals, contain the filterable, infective agent. The
      lesions present in the inoculated organs conform to those described in our first
      publication. In addition, the lymph glands adjacent to the salivary glands on the
      uninoculated side were sometimes found to be swollen and to exhibit microscopic
      lesions. Probably the involvement resulted from salivary and lymphatic infection.
      The "virus" of parotitis was detected most readily in the saliva during the first
      3 days of the disease, less easily on the 6th day, and not at all on the 9th day.
      It was detected also in the blood of patients showing marked constitutional
      symptoms, and in the saliva of a case of recurrent mumps at the periods of
      enlargement of the parotid glands, but not 2 weeks after the swelling had
      subsided. It was not detected in the cerebrospinal fluid.

PMID- 19868266
TI  - THE ENCYSTMENT OF DYSENTERY AMEBAE IN VITRO.
AB  - Dysentery amebae may live for 72 hours in vitro. The transition of the large
      vegetative forms into the cyst may be observed in vitro. The large vegetative
      ameba always passes into an intermediate stage before assuming the small
      vegetative form. The atypical forms are dysentery amebas with abnormal nuclei and
      cytoplasm. When circumstances are unfavorable encystment takes place. Under
      favorable conditions, on the other hand, they may again change into typical
      forms. The majority of the "degenerative" forms of Hartmann cannot be so classed.
      According to our observation, they represent forms which have been described
      here. Hartmann's Entamoeba histolytica is really a typical transitional form of
      Entamoeba tetragena. The origin and significance of the central vacuole have been
      elucidated. Nuclear division of the dysentery ameba proceeds in three ways. The
      typical forms divide on the whole mitotically, and the atypical a mitotically or
      in a primitively mitotic manner.

PMID- 19868267
TI  - A NEW NON-PATHOGENIC TETRAGENOUS AMEBA. I.
AB  - The non-pathogenic tetragenous ameba described here multiplies in the intestine
      of man, without producing any noticeable symptoms of dysentery. This non
      pathogenic ameba is distinguished morphologically and biologically from Entamoeba
      tetragena Viereck and Entamoeba coli Losch emend. Schaudinn. The vegetative forms
      of the non-pathogenic tetragenous ameba may be divided into two groups, large and
      small. The large vegetative form is found in the normally evacuated or the
      diarrheal stools obtained after purgation. The small form is found in the soft
      stools. This form may be transformed into cysts, or may reproduce itself by
      binary fission. Cysts are found in relatively large numbers in the soft and
      formed stools. Experimentally, the new tetragenous ameba may be readily
      distinguished from the pathogenic variety. The vegetative forms of the dysentery
      ameba produced the disease in 91 per cent of cases when introduced per anum, and
      in 50 per cent where the cysts were introduced per os. Similar infection
      experiments undertaken on twenty-three young cats, i.e. ten experiments with the
      vegetative form of the non-pathogenic tetragenous ameba per anum, and thirteen
      experiments with the cysts per os, failed to produce pathological conditions. The
      intestines of the animals macroscopically and histologically failed to show any
      of the changes of dysentery. Hence we may conclude that the new type of
      tetragenous ameba described here is non-pathogenic for man and for young cats.

PMID- 19868268
TI  - THE RAT AND POLIOMYELITIS: AN EXPERIMENTAL STUDY.
AB  - The central nervous organs and other viscera of six rats, collected in a district
      in Greater New York in which many cases of epidemic poliomyelitis occurred, have
      been proved incapable of inciting, on inoculation, experimental poliomyelitis in
      Macacus rhesus monkeys. The virus of poliomyelitis injected into the brain of
      white rats does not survive there as long as 4 days in a form or in amounts
      sufficient to cause infection when inoculated intracerebrally into monkeys. The
      failure of the virus injected into the brain of rats to incite infection in
      monkeys is not due to the quantity introduced, since at the expiration of 1(1/2)
      hours after the injection, the excised inoculation site when injected into the
      monkey caused typical experimental poliomyelitis. It does not appear probable,
      therefore, that the rat acts in nature as the reservoir of the virus of
      poliomyelitis.

PMID- 19868269
TI  - SPIROCHAETA HEBDOMADIS, THE CAUSATIVE AGENT OF SEVEN DAY FEVER (NANUKAYAMI) :
      FIRST PAPER.
AB  - A new species of spirochete which we have called Spirochaeta hebdomadis has been
      described as the specific etiological agent of seven day fever, a disease
      prevailing in the autumn in Fukuoka and other parts of Japan. This spirochete is
      distinguishable from Spirochaeta icterohaemorrhagiae to which it presents certain
      similarities. Young guinea pigs are susceptible to inoculation with the blood of
      patients and to pure cultures of the spirochete, and those developing infection
      exhibit definite symptoms suggestive of those of seven day fever in man. The
      blood serum of convalescents from seven day fever contains specific immune bodies
      acting spirochetolytically and spirocheticidally against the specific
      spirochetes, but not against Spirochaeta icterohaemorrhagiae. The field mouse
      (Microtus montebelli) is the normal host of the spirochetes, which have been
      detected in the kidneys and urine of 3.3 per cent of the animals examined. The
      endemic area of prevalence of seven day fever corresponds with the region in
      which field mice abound.

PMID- 19868270
TI  - A REPORT ON ANTIMENINGITIS VACCINATION AND OBSERVATIONS ON AGGLUTININS IN THE
      BLOOD OF CHRONIC MENINGOCOCCUS CARRIERS.
AB  - 1. A meningococcus vaccine suspended in salt solution has been given
      subcutaneously as a prophylactic to about 3,700 volunteers in three injections of
      2,000 million, 4,000 million, and 4,000 or 8,000 million cocci at weekly
      intervals. 2. These doses rarely caused more than the mildest local and general
      reactions. Exceptionally a more severe reaction emphasized the presence of an
      unusual individual susceptibility to the vaccine. In such instances the symptoms
      were in part those of meningeal irritation and sometimes simulated the onset of
      meningitis. 3. Specific meningococcus agglutinins have been demonstrated in the
      blood serum of vaccinated men as compared with normal controls. 4. Moreover,
      agglutinins have been demonstrated in the blood serum of chronic carriers of the
      meningococcus. Evidence is thus brought forward that the relative immunity of
      chronic carriers to epidemic meningitis may be due to the presence of specific
      antibodies in the blood stream.

PMID- 19868271
TI  - FURTHER INVESTIGATIONS ON THE ORIGIN OF TUMORS IN MICE : V. THE TUMOR RATE IN
      HYBRID STRAINS.
AB  - 1. In order to test our previous conclusions concerning the tumor rate in hybrid
      strains, we carried out additional hybridizations. For this we selected strains
      which differed markedly in their tumor rate and which had been followed through a
      number of generations and found constant in their behavior. Hybridizations
      between strains or families of a similar (either high, medium, or low) tumor rate
      served as control experiments. In these cases the offspring showed a tumor rate
      similar to that of the parents. 2. In selecting for hybridization various groups
      of Cream mice representing a very low tumor strain and English Sable mice
      representing a high tumor strain, we obtained in the majority of cases hybrid
      strains with a tumor rate intermediate between that of both parent strains. In a
      few instances it approached somewhat the high tumor strain of the English, and in
      a few others the low tumor rate of the Cream. 3. In several hybrids between the
      high tumor strain English and the low tumor strain Silver, the latter of which
      was split off from the English, the high tumor rate of the English prevailed. A
      number of mice which served for hybridization were followed throughout their life
      and found to behave typically as to tumor rate. 4. If we omit the strains in
      which both parents had a similar tumor rate, we found the higher tumor rate to be
      dominant in twenty-four hybrids. In seventeen of these the mother strain
      dominated, and in seven the father strain. In nineteen hybrid strains the tumor
      rate was intermediate. In ten strains the lower tumor rate dominated. In eight of
      these the mother strain prevailed and in two the father strain. The low tumor
      rate was, therefore, dominant in approximately 18 per cent of the strains. 5.
      There does not seem to be a fixed rule as to dominance in the tumor rate. In a
      considerable number of cases, and especially in well analyzed cases, the result
      was intermediate. 6. Altogether in twenty-five of our hybrid strains the mother
      strain, and in nine strains the father strain prevailed. In nineteen strains the
      result was intermediate. We conclude that both father and mother strain may
      dominate and that the tumor rate is not in the strict sense of the term a sex
      linked character. However, the fact that the mother strain prevailed in a much
      larger number of our cases than the father strain, and that several times (but
      not in all cases), in reciprocal crosses, the hybrids followed the tumor rate of
      the mother strain, suggests the possibility that as far as the hereditary
      transmission of mammary cancer in mice is concerned, the mother may be more
      potent than the father, and that perhaps under certain quantitatively varying
      conditions the mother strain may dominate over the father strain. This statement
      is merely a tentative conclusion at the present time and needs further
      investigation. 7. The results of these investigations confirm our previous
      conclusion that in the majority of the crosses which we observed, the cancer rate
      is either intermediate between those of father and mother strain, or that it
      follows the tumor rate of the parent with the higher rate and only in a
      relatively small number of instances the cancer rate follows that of the parent
      strain with the lower tumor rate. On the whole, the heredity of cancer rate and
      cancer age follows the blending type of hereditary transmission. 8. While there
      is a distinct relation between high tumor rate and early cancer age, our
      observations make it probable that cancer rate and cancer age are to some extent
      independent of each other. 9. On the whole the different generations, including
      F(1) and F(2) of the various hybrid strains, showed a concordant tumor rate and
      tumor age. 10. If we consider, then, our results as a whole, we may conclude that
      in crossing strains which differ in their tumor rate no rule of dominance which
      applies equally to all cases seems to exist. In a certain number of crosses the
      results are undoubtedly intermediate. In these instances the tumor rate and to
      some extent also the tumor age behaves in a manner similar to characters which
      differ in father and mother merely in quantity as in the length of organs. From
      such intermediate results all kinds of gradations exist, leading on one side to
      dominance of the strain with the higher tumor rate and on the other side to
      dominance of the strain with the lower tumor rate. However, in our experiments
      dominance of the strains with the higher tumor rate greatly predominated over the
      opposite extreme. 11. Our results on the whole are, therefore, in certain
      respects comparable with the inheritance of sex which Goldschmidt studied in
      hybrid strains of the gypsy mother. Here also all gradations from the male to the
      female were observed in the offspring. Goldschmidt assumes that in different
      hybrids there are created different quantities of certain substances which like
      enzymes determine according to their quantity the velocity of chemical reactions
      and the amount of certain substances produced. The latter determine in the
      hybrids the quantitative variations in the character which is analyzed. According
      to Goldschmidt, multiple allelomorphs, which in our experiments seem to determine
      the heredity of spontaneous cancer, depend upon differences in the quantity of a
      substance present in the different individuals or varieties. In whatever way we
      may conceive of the character of multiple allelomorphs, our results make it
      probable that multiple factors are involved in the heredity of cancer in mice.

PMID- 19868272
TI  - THE STABILITY OF THE ACID-BASE EQUILIBRIUM OF THE BLOOD IN NATURALLY NEPHROPATHIC
      ANIMALS AND THE EFFECT ON RENAL FUNCTION OF CHANGES IN THIS EQUILIBRIUM : I. A
      STUDY OF THE ACID-BASE EQUILIBRIUM OF THE BLOOD IN NATURALLY NEPHROPATHIC ANIMALS
      AND OF THE FUNCTIONAL CAPACITY OF THE KIDNEY IN SUCH ANIMALS FOLLOWING AN
      ANESTHETIC.
AB  - 1. The naturally acquired chronic glomerulonephropathies of the dog are not due
      to an acid intoxication. 2. Such an injury renders the acid-base equilibrium of
      the animal unstable and susceptible to an agent such as an anesthetic which tends
      to induce an acid intoxication. 3. When naturally nephropathic animals are
      anesthetized by Grehant's anesthetic, the principal anesthetic ingredient of
      which is chloroform, the animals develop an acid intoxication, and become anuric
      and non-responsive to diuretic substances. 4. The development of the anuria has
      been constantly associated with swelling, vacuolation, and necrosis of the
      convoluted tubule epithelium. 5. In the kidneys of these animals there occurs an
      accumulation of fat which is largely confined to the ascending limbs of Henle's
      loops and which shows a quantitative relation with the degree of acid
      intoxication.

PMID- 19868273
TI  - THE STABILITY OF THE ACID-BASE EQUILIBRIUM OF THE BLOOD IN NATURALLY NEPHROPATHIC
      ANIMALS AND THE EFFECT ON RENAL FUNCTION OF CHANGES IN THIS EQUILIBRIUM : II. A
      STUDY OF THE EFFICIENCY OF AN ALKALI TO PROTECT THE NATURALLY NEPHROPATHIC KIDNEY
      AGAINST THE TOXIC EFFECT OF AN ANESTHETIC.
AB  - 1. A 0.9 per cent solution of sodium chloride when given intravenously to
      anesthetized naturally nephropathic animals is not effective in preventing the
      development of an acid intoxication and the associated kidney injury. 2. A
      solution of sodium carbonate equimolecular with a 0.9 per cent solution of sodium
      chloride when given intravenously to anesthetized naturally nephropathic animals
      confers a variable degree of protection to the kidney. 3. The degree of
      protection conferred by the alkaline solution is associated with the ability of
      the solution to maintain a normal acid-base equilibrium of the blood of the
      anesthetized animal.

PMID- 19868274
TI  - ACID PRODUCTION GRAPHICALLY REGISTERED AS AN INDICATOR OF THE VITAL PROCESSES IN
      THE CULTIVATION OF BACTERIA.
AB  - WE MAY FORMULATE THE RESULTS AS FOLLOWS: 1. Bacillus paratyphosus in lactose
      peptone-water causes a fall in the curve. The explanation of this must be left to
      later investigations. 2. Bacillus paratyphosus in glucose-peptone-water shows at
      the beginning a rise similar to that produced by coli, but a fall in the curve
      follows. 3. If Bacillus coli is added to a 24 hour paratyphosus lactose culture a
      very long latent period is obtained before the formation of acid by coli becomes
      apparent, presumably due to accumulated basic metabolic products. 4. If Bacillus
      coli is added to a 24 hour paratyphosus glucose culture the curve is not changed
      from the normal to any perceptible degree. 5. Bacillus coli communis and Bacillus
      paratyphosus in lactose in mixed cultures give a longer latent period than coli
      alone. The first ascending part of the curve is due to acid formation by the coli
      which in the beginning is dominant. Later paratyphosus dominates and causes an
      ultimate decline in the curve. 6. Bacillus coli communis and Bacillus
      paratyphosus in glucose in mixed culture behave like Bacillus paratyphosus in
      pure culture. The purpose of these investigations has been for the present to
      show the usefulness of the method. It is hoped that by these investigations
      material of particular interest relating to the biochemical and physiological
      processes within the bacterial culture will be obtained.

PMID- 19868275
TI  - EXPERIMENTAL CHEMICAL PNEUMONIA.
AB  - It is obvious from the experiments reported that concentrations of chloramine-T
      solutions, even more dilute than those which are well borne by the nasopharyngeal
      mucosa, are injurious to the pulmonary tissue when introduced directly into. the
      bronchi in large volume. The pulmonary lesions produced are of the nature of an
      extensive bronchopneumonia which progresses during the first 2 days after
      injection of the chemical and then regresses, to disappear, as a rule, by the 7th
      day. Similar pulmonary lesions were produced by intrabronchial insufflation of
      Dakin's solution of hypochlorite of sodium. These studies taken in conjunction
      with the earlier ones of Kline and Meltzer in which aleuronat, starch, egg yolk,
      and lecithin were insufflated into the lungs, show that pulmonary inflammation
      may be induced by various chemical substances-with the following differences.
      Aleuronat and starch set up consolidations containing much fibrin, as is the case
      with virulent pneumococci; egg yolk and lecithin gave lesions with little fibrin,
      as is the case with avirulent pneumococci. Both series of substances produced
      lobar pneumonia, while the pulmonary lesions induced by chloramine-T and sodium
      hypochlorite were of the nature of bronchopneumonia. The consolidations of the
      lung produced by chemical substances differ from infectious pulmonary
      inflammations only in their sterility. These experimental results strongly
      suggest the view that the anatomical findings in pneumonia represent a part of a
      mechanism of defense and repair which the animal body creates in its struggle
      against infection and intoxication.

PMID- 19868276
TI  - EFFECT OF INTRABRONCHIAL INSUFFLATION OF SOLUTIONS OF SOME INORGANIC SALTS.
AB  - Intrabronchial injections of isotonic as well as of hypotonic solutions of sodium
      chloride or even of distilled water cause no pulmonary lesions. Intrabronchial
      injections of mercuric chloride even in a dilution of 1:10,000 cause a marked
      pulmonary lesion. The lesion is not of an inflammatory character; it consists of
      congestion, formation of thrombi, and hemorrhage. Intrabronchial injections of
      hypertonic solutions of sodium chloride as well as of sodium sulfate cause, in
      most instances, no lesions whatsoever. In a smaller number of cases in which
      moderate lesions were present they may have been due either to a previous
      infection (distemper) or to some predisposing cause (winter months).
      Intrabronchial injection of magnesium salts apparently tends to cause moderate
      pulmonary lesions (bronchopneumonia). This seems especially true of magnesium
      sulfate.

PMID- 19868277
TI  - THE SPIROCHETAL FLORA OF THE NORMAL FEMALE GENITALIA.
AB  - The spirochetal flora of normal female genitalia is similar to that of the male
      and consists of Treponema calligyrum, Treponema minutum, and Spironema
      refringens. The types are present in varying proportions, but the calligyrum
      usually predominates, and the refringens is the least frequent. The female
      genitalia are much richer generally in the number of spirochetes than the male.

PMID- 19868278
TI  - A COMPARATIVE STUDY OF EXPERIMENTAL PROPHYLACTIC INOCULATION AGAINST LEPTOSPIRA
      ICTEROHAEMORRHAGIAE.
AB  - Guinea pigs were inoculated with suspensions of Leptospira icterohaemorrhagiae
      obtained from pure cultures of several different strains, in order to determine
      whether or not an active immunity against a subsequent infection with virulent
      organisms would develop in the vaccinated animals. The experiments were so
      arranged as to make possible a determination of the existence of immunity against
      homologous strains as well as against the strains not employed as vaccine, and a
      brief quantitive estimation of the degree and duration of the immunity in
      relation to the quantities of the vaccines inoculated. Following the general rule
      of prophylactic inoculations with various pathogenic organisms, the inoculations
      were repeated subcutaneously on three consecutive occasions at intervals of 5
      days. With respect to the amounts of vaccine, the experiments were divided into
      three groups for each vaccine, one group receiving three doses of 0.5 cc., the
      second three of 0.05 cc., and the third three of 0.005 cc. Four different strains
      were employed as vaccines, American Strain 1, American Strain 2, and one each of
      the Japanese and the European strains. The determination of the development,
      degree, and duration of the immunity was made by inoculating intraperitoneally
      several minimum lethal doses of each of the five following strains: American
      Strains 1, 2, and 3, the Japanese, and the European strains. The virulence of the
      different strains varied considerably, the strongest being the Japanese strain,
      which killed the guinea pig in a dose of 0.00001 cc., and the weakest American
      Strain 3, the minimum lethal dose of which was as large as 0.01 cc. The
      vaccinated guinea pigs were tested for immunity at the end of 2, 4, and 8 weeks
      after the last inoculation. The results obtained show that three successive
      inoculations of 0.5 cc. of the emulsions of killed cultures of Leptospira
      icterohaemorrhagiae into guinea pigs rendered them completely resistant to a
      subsequent infection with the virulent cultures of both homologous and
      heterologous strains. With 0.05 cc. the protection was not so general, the
      animals succumbing to an experimental infection with some heterologous strains
      while resisting the homologous and other heterologous strains. The animals which
      were vaccinated with 0.005 cc. survived the infection experiments with the
      homologous strains in the case of American Strain 1 and the Japanese strain, but
      they were not protected against any other strains. The vaccines of other strains
      were unable to immunize the guinea pigs so highly even against their homologous
      strains, when the amount of each inoculation was only 0.005 cc., but 0.05 cc.
      conferred complete protection against the same strains. It may be concluded,
      therefore, that when a sufficient quantity of killed cultures of Leptospira
      icterohaemorrhagiae is given, the guinea pigs will become immune to all strains
      of the same organism, but that smaller quantities may protect them against
      homologous but not against heterologous strains. A close analysis reveals the
      existence of group or type affinities among different strains which can be
      brought ' out by immunizing the animals with smaller quantities of killed
      cultures. In the present series of experiments American Strains 1 and 3 form one
      group, American Strain 2 and the European strain another, and the Japanese strain
      a third, which is also closely allied to the first group. In order to insure
      universal immunity it is wise to employ as many group or type cultures as
      possible in the preparation of vaccines, a polyvalent vaccine being recommended.
      It is not improbable that the strain recently encountered in Lorient, France, is
      an unusually deviated type of Leptospira icterohaemorrhagiae, and that if
      successfully cultivated and used as vaccine in sufficient amount it might protect
      the animals against other strains of the same organism. The active immunity
      induced in the vaccinated guinea pigs was found to persist for at least 8 weeks
      after the last inoculation. It will no doubt last for a much longer period.

PMID- 19868279
TI  - A SPECIFIC POISON IN THE LIVER EXTRACTS OF RABBITS INOCULATED WITH TYPHOID AND
      PRODIGIOSUS BACILLI INTRAVENOUSLY.
AB  - 1. The livers of rabbits inoculated with cultures of Bacillus typhosus or
      Bacillus prodigiosus under certain conditions contain a toxic substance
      extractable with salt solution. When the toxic extracts are injected
      intravenously into normal rabbits the latter animals develop symptoms resembling
      those of anaphylactic shock and succumb. The lethal doses of the toxic extracts
      are far smaller than those of normal liver extract. 2. The livers of rabbits
      injected with typhoid antigen also yield a toxic extract. 3. Boiling as well as
      filtration through a Berkefeld filter only partially detoxicates the extract. 4.
      Tolerance to one to two lethal doses of the poisonous extracts can be induced by
      cautious immunization. 5. Rabbits actively immunized to Bacillus typhosus or
      Bacillus prodigiosus usually resist one lethal dose of the homologous liver
      poison; and animals tolerant to the typhoid liver poison resist one minimum
      lethal dose at least of Bacillus typhosus. 6. Typhoid immune serum is not
      detoxicating either in vivo or in vitro for the typhoid liver poison. 7. The
      liver poisons are specific, since rabbits actively immunized to either Bacillus
      typhosus or Bacillus prodigiosus withstand at least one minimum lethal dose of
      the homologous but not of the heterologous-liver poisons.

PMID- 19868280
TI  - AN IMPROVEMENT IN THE METHOD OF ISOLATING AND RECOVERING THE BACILLUS OF CATTLE
      ABORTION THROUGH GUINEA PIGS.
AB  - 1. Bacillus abortus Bang can be regularly recovered from guinea pigs inoculated
      with material containing the bacillus within 3 to 4 weeks. 2. The method is
      especially useful in recovering the organism from fetal membranes which, as a
      rule, are obtained after having come in contact with fecal matter, bedding, etc.
      3. The spleen is the organ in which the bacteria are regularly present and in
      largest numbers. Cultures must be made from it to ensure success.

PMID- 19868281
TI  - NEW THORACIC MURMURS, WITH TWO NEW INSTRUMENTS, THE REFRACTOSCOPE AND THE PARTIAL
      STETHOSCOPE.
AB  - 1. An understanding of the physics of sound is essential for a better
      comprehension of refined auscultation, tone analysis, and the use of these
      instruments. 2. The detection of variations of the third heart sound should prove
      a valuable aid in predicting mitral disease. 3. The variations of the outflow
      sound should prove a valuable aid in determining early aortic lesions with the
      type of accompanying intimal changes. 4. The character of chamber timbre as
      distinct from loudness heard as the first and second heart sounds denotes more
      often the condition of heart muscle, and must not be confounded with valvular
      disease. 5. The full significance of sound shadows is uncertain. Cardiac sound
      shadows appear normally in the right axilla and below the left clavicle. Their
      mode of production is quite clear. 6. Both the third heart sound and the outflow
      sound may be heard with the ordinary stethoscope.

PMID- 19868282
TI  - A NEW TYPE OF SYRINGE, ESPECIALLY ADAPTED FOR INTRAVENOUS INJECTIONS OR THE
      ASPIRATION OF BLOOD.
AB  - In rabbits destroying transfused blood constantly during a period of many months
      a pronounced and widespread siderosis ensues, practically identical with that
      characterizing human hemochromatosis. The findings do not indicate the ultimate
      cause of this disease, but they throw light on its various features and its
      course, and suggest a means for its diagnosis.

PMID- 19868283
TI  - EXPERIMENTAL HEMOCHROMATOSIS.

PMID- 19868284
TI  - URINARY SIDEROSIS : HEMOSIDERIN GRANULES IN THE URINE AS AN AID IN THE DIAGNOSIS
      OF PERNICIOUS ANEMIA, HEMOCHROMATOSIS, AND OTHER DISEASES CAUSING SIDEROSIS OF
      THE KIDNEY.
AB  - In diseases which bring about a siderosis of the kidney there are ordinarily
      present in the urinary sediment cells containing granules of hemosiderin, and
      often many free granules as well. The finding has proved useful in the diagnosis
      of hemochromatosis and will probably be of service in the recognition of
      pernicious anemia, and possibly some other diseases. But in this relation the
      fact should be emphasized that urinary siderosis, as one may term it, is the
      indication of a renal condition, not of a disease.

PMID- 19868285
TI  - A RAPID DIFFERENTIAL METHOD FOR THE ISOLATION OF BACILLUS INFLUENZAE.

PMID- 19868286
TI  - THE EFFECT OF FEEDING SUGAR UPON THE ESTERASE CONTENT OF THE BLOOD SERUM AND
      ORGANS IN PHOSPHORUS POISONING.
AB  - 1. Clear, filtered glycerol extracts of chopped liver, spleen, and kidney contain
      an ester-splitting ferment. 2. The esterase content of extracts of the liver and
      spleen of normal dogs is reasonably constant. 3. The amount of esterase in the
      liver does not appear to vary to any great extent from the normal, in poisoning
      with chloroform and phosphorus. 4. Feeding large quantities of sugar and
      increasing the amount of glycogen in the liver is accompanied by a marked
      increase in the esterase content of that organ. This increase is also evident in
      phosphorus-poisoned animals which have been fed large amounts of sugar. 5. The
      feeding of sugar does not prevent the increase in esterase in the blood serum of
      animals poisoned with phosphorus. 6. The esterolytic power of extracts of the
      kidney varies considerably in different dogs.

PMID- 19868287
TI  - THE PEPTOLYTIC POWER OF LIVER, SPLEEN, AND KIDNEYS IN POISONING BY PHOSPHORUS AND
      CHLOROFORM.
AB  - 1. Glycerol extracts of liver, spleen, and kidney contain an ereptic ferment
      capable of splitting peptone into amino-acids. 2. Poisoning by phosphorus appears
      to reduce the ereptic power of the liver, and to a less extent that of the
      kidneys. 3. Poisoning by chloroform appears to have no appreciable effect upon
      the ereptase content of the liver, spleen, or kidneys. 4. Feeding of sugar to
      normal animals has little or no effect upon the ereptic power of the liver,
      spleen, or kidneys. 5. Feeding of sugar before and after poisoning with
      phosphorus appears to prevent the reduction of ereptic power of the liver.

PMID- 19868288
TI  - RELATIVE IRRITANT PROPERTIES OF THE CHLORINE GROUP OF ANTISEPTICS.
AB  - 1. The use of the ears of rabbits is proposed in testing the irritant effect of
      antiseptics. 2. It is necessary, because of individual variations, to use
      solutions having definite irritant actions as controls. 3. 0.5 per cent sodium
      hypochlorite solutions have minimum irritant effects over a range of alkalinity
      of from about 100 to 1,000 times that of water (pH about 9 to 10). Solutions may
      be adjusted within these limits by use of the end-points of powdered
      phenolphthalein, of alcoholic solutions of either o-cresolphthalein or
      phenolphthalein. 4. Sodium hypochlorite solutions kept within the above range of
      alkalinity by either borate or carbonate buffer salts, i.e. Dakin's solution,
      show the same irritative properties whether made from bleaching powder and sodium
      carbonate, or from chlorine and sodium carbonate. 5. Electrolytically prepared
      solutions of the same concentration have similar irritant action. 6. Solutions,
      however, that have an alkalinity less than that indicated by the end-point of
      alcoholic phenolphthalein solutions (pH of 8.5 to 8.8) or greater than that
      indicated by the end-point to powdered phenolphthalein (pH of 10.2) are intensely
      irritating. 7. 0.5 per cent sodium hypochlorite solution from which most of the
      calcium has been precipitated and calcium hypochlorite solution of equivalent
      hypochlorite concentration are only slightly irritating. 8. 2 per cent chloramine
      T solution has no irritant action. 9. 5 per cent dichloramine-T in chlorcosane
      and chlorcosane alone irritate rabbit ears to a slight degree only.

PMID- 19868289
TI  - SPIRILLA ASSOCIATED WITH DISEASE OF THE FETAL MEMBRANES IN CATTLE (INFECTIOUS
      ABORTION).
AB  - Spirilla of identical morphological and cultural characters have been isolated in
      pure culture from the fetuses of fourteen cases of abortion. The condition of the
      fetus is much the same whether spirilla or the bacilli of abortion are present.
      This condition is probably due in both cases to interference with the placental
      circulation. The injurious action of the etiological factor when spirilla are
      present is limited to the fetal membranes, more particularly the chorion.
      Definite lesions of the fetus were not detected. The spirilla gain access to the
      digestive and respiratory organs of the fetus when the latter swallows the
      amniotic fluid. More rarely they are disseminated through the body, probably
      through the circulation. The spirilla will grow in certain culture media only
      under reduced oxygen tension, readily secured by sealing the ordinary culture
      tubes with sealing wax. Laboratory animals (mammals) are refractory. The precise
      relation of the spirillum to the pathologic process remains to be more definitely
      formulated. Since the spirillum was first isolated, twenty-seven cases have been
      found associated with Bacillus abortus and fourteen with the spirillum. In none
      was a mixed infection with both organisms detected. The spirillum has been
      isolated only from the second or succeeding pregnancies. Table I summarizes the
      data collected thus far. It gives by. number the male and shows that the
      spirillum is not associated with any one bull. The spirillum has been found in
      fetuses of various ages as shown in Column 3. The distribution of spirilla as
      shown by cultures is given, the sign + indicating pure cultures, the sign no
      growth. The guinea pig inoculations are shown to be uniformly negative as regards
      Bacillus abortus.

PMID- 19868290
TI  - STUDIES IN BOVINE MASTITIS : III. INJECTION OF THE UDDER WITH MICROCOCCI AND
      OTHER MICROORGANISMS.
AB  - Aside from the streptococci, micrococci have been the next most frequent group of
      organisms isolated from inflamed udders. They produce various types of disease.
      Some give rise to only a mild catarrh of the larger milk ducts and cystern, while
      others produce more or less severe parenchymatous inflammation. On the whole, the
      prognosis is more favorable with micrococcic infection than with that associated
      with streptococci. Cases of considerable severity have, however, been attributed
      to staphylococci. Micrococci similar in many respects to those associated with
      mastitis have been found to occur in the normal udder. This has led Savage to
      question their true etiological significance. In many instances micrococci may
      gain access to the udder and produce slight disturbances that are entirely
      overlooked. Even more severe changes may follow infection. After recovery the
      organisms still remain in the milk. This was observed in the case of Cow 60
      infected with staphylococci. One frequently observes the elimination of
      streptococci from the udder even after apparent recovery from an attack of
      streptococcic mastitis. Doubtless streptococci and micrococci observed in these
      udders would be classed as belonging to the normal flora. Even though micrococci
      do occur in supposedly normal udders Evans has shown that many are pathogenic for
      rabbits. The introduction of these organisms into the udders of non-resistant
      individuals might well give rise to more or less intense inflammation. The
      multiplication would doubtless be rapid until resistance had been established. In
      addition to the micrococci two other groups of rod-shaped organisms have been
      found associated with udder inflammation. In two instances Bacillus coli has been
      isolated from cases of mastitis and in another Bacillus lactis aerogenes. In
      four, tiny motile Gramstaining microorganisms have been obtained in pure culture.
      Two of these strains (Nos. C.79 and M.44) have been identified as Bacillus
      pyogenes.

PMID- 19868291
TI  - STUDIES IN BOVINE MASTITIS : IV. THE SOURCES OF INFECTION IN STREPTOCOCCIC
      MASTITIS.
AB  - 1. The principal sources of streptococcic infection, aside from clinical cases,
      are apparently normal cows which carry the virus in the udder. 2. These carriers
      may be grouped as follows: (a) those that have been infected recently and have
      not yet developed symptoms; (b) those that have suffered from inflammation of the
      udder and after recovery still harbor streptococci; (c) those that have had no
      clinical history of mastitis. There is some evidence to lead one to regard the
      latter group as naturally immune. 3. A milker may readily carry streptococci on
      his hands from an infected to an uninfected cow. 4. The vaginae of 34 of the 64
      cows examined contained non-hemolytic streptococci. Of the 34 strains isolated 32
      differed in their cultural characters and agglutination affinities from those
      associated with mastitis. The other two strains may be regarded as of etiological
      significance. 5. In no instance have hemolytic streptococci been isolated from
      the vagina.

PMID- 19868292
TI  - THE SURVIVAL OF THE HOG-CHOLERA VIRUS IN LABORATORY ANIMALS, PARTICULARLY THE
      RAT.
AB  - The attempts to demonstrate the virus of hog-cholera in rabbits 12 days after
      intravenous and intraabdominal inoculations were unsuccessful. Likewise the
      attempts to show that the virus might be found in the guinea pig 6 and in the
      pigeon 7 days after inoculation were negative. It was shown, however, that the
      virus can be found in the bodies of white rats for at least 7 days after either
      intraabdominal or intracerebral inoculations. One attempt to demonstrate it after
      10 days was negative. From the fact that the rats show no evidence of illness
      such as loss in weight, pyrexia, or visible pathological changes, and that after
      either intraabdominal or intracerebral inoculation the virus is only found in the
      abdominal organs and possibly only in the spleen, it seems likely that it does
      not multiply but that in the rat tissue, particularly in the spleen, it is not
      destroyed so rapidly as in the organs of other animals. Careful study of the
      records fails to show that passing one strain of virus alternately through pigs
      and rats for three transfers in each species changes the virulence for swine or
      causes the virus to become virulent for rats. Attempts to introduce the virus
      into the body of the rat by feeding virulent material and an attempt to pass the
      virus from one lot of rats to another were unsuccessful, so that we have evidence
      from the experiment that the rat does not play a part in the transmission of hog
      cholera.

PMID- 19868293
TI  - A STUDY OF PARATYPHOID BACILLI ISOLATED FROM CASES OF HOG-CHOLERA.
AB  - During the course of some experimental work on hog-cholera, paratyphoid bacilli
      were isolated from 16 per cent of the pigs. Culturally these organisms are the
      same as paratyphoid 18 isolated from man, while they show several differences
      from hog-cholera bacilli. In their slight pathogenic effect on rabbits they also
      differ from the hog-cholera bacillus. In their agglutination in sera produced by
      the injection of living cultures, one of the cultures, isolated from a chronic
      case, corresponds to Bacillus enteritidis, while the other five are apparently in
      a class by themselves. They resemble paratyphoid beta more closely than hog
      cholera bacilli, but the type of clumps formed and absorption experiments show
      that they are different from either. Whether these differences are enough to make
      it necessary to put them into a class by themselves is questionable, but the fact
      that when injected into rabbits they produce an immunity to the hog-cholera
      bacillus, while paratyphoid beta does not, is additional evidence in favor of
      such a classification. Complement fixation experiments have been of little value
      in differentiating the members of this group, but on the contrary show their
      close relationship. It seems probable that some of the cultures that are
      described in the literature as hog-cholera bacilli really belong to this group,
      which would account for much of the confusion that exists in the classification
      of the interesting, truly pathogenic bacillus that at one time was thought to be
      the cause of hog-cholera and in the series of animals with which we have worked
      has not appeared once. Whether the ingestion of pork containing these bacilli
      would cause disease in man is a question that can only be decided by a more
      careful bacteriological study of the organisms causing food poisonings and
      paratyphoid fever.

PMID- 19868294
TI  - STANDARDIZATION OF ANTIMENINGOCOCCIC SERUM.
AB  - Experiments were made for the purpose of testing the reaction of protection
      against infection as a measure of potency of antimeningococcic serum. The results
      of the experiments were extremely variable and bore no relation to the quality of
      the sera as determined by the period of immunization of the horses from which
      they were obtained, or the indications of efficiency based upon their employment
      in human cases of epidemic meningitis. The results also failed entirely to
      conform to the agglutination titer of the sera tested and to be affected by the
      different type forms of the meningococci. We regard the protective power for
      laboratory animals of the antimeningococcic serum as an unsuitable index of its
      value in human medicine and as inferior to the agglutination titer as a standard
      of potency.

PMID- 19868295
TI  - A STUDY OF THE CHANGES IN VIRULENCE OF THE PNEUMOCOCCUS AT DIFFERENT PERIODS OF
      GROWTH AND UNDER DIFFERENT CONDITIONS OF CULTIVATION IN MEDIA.
AB  - It has been possible by rapid transfers alone, not only to maintain the virulence
      for mice of the pneumococcus in artificial media but also to restore a certain
      degree of virulence to cultures previously rendered non-virulent by less rapid
      transfers in the same medium. For these results the presence of enriching fluids
      such as blood or serum is not required. In addition it has been shown that
      attenuated cultures, which had been repeatedly demonstrated to be avirulent for
      mice at the 24 hour period of growth, exhibited marked pathogenicity if injected
      during, or especially at the commencement of the period of maximum growth when
      the growth energy may be considered at its height. In these cultures, however,
      the increase in virulence was usually less than in others transferred repeatedly
      at frequent intervals. The significance of these results is not necessarily
      limited to pneumococcus infections. Other lines of investigation are suggested
      which may possibly help to clarify certain conceptions of the relation which the
      different activities of the bacterial cell as an agent of infection bear to one
      another and to the host in various infectious diseases. Although the pneumococcus
      may offer an especially striking example for purposes of demonstration by
      experiment, it is not probable that the close relation between the vegetative
      power or growth energy of the pneumococcus and its pathogenic power is peculiar
      to this organism. The vegetative power may depend upon many conditions affecting
      both the host and the bacterial agent of infection. Different species of bacteria
      may acquire or develop it in different degrees under different conditions. But it
      must assuredly form the basis not only of the essentially parasitic but also of
      the more special toxicogenic activities of the bacteria.

PMID- 19868296
TI  - EFFECT OF DRY HEAT ON THE BLOOD COUNT IN ANIMALS : III. STUDIES ON LYMPHOID
      ACTIVITY.
AB  - Animals subjected to dry heat for a short period show a sharp fall in the total
      white blood count, both the polymorphonuclear leucocytes and the lymphocytes
      taking part in the fall. Following this there is a slow recovery on the part of
      the polymorphonuclear leucocytes, which generally require several weeks to regain
      their normal number. The lymphocytes rise rapidly after the initial fall and
      continue to rise for 2 or 3 weeks. This increase often amounts to a gain of over
      200 to 300 per cent above the normal count for the animal. The observations were
      made on mice, rats, and guinea pigs. The circulating lymphocytes during the more
      active stage of stimulation after heating show numerous examples of amitotic
      division.

PMID- 19868297
TI  - EFFECTS OF LARGE DOSES OF X-RAYS ON THE SUSCEPTIBILITY OF THE MONKEY TO
      EXPERIMENTAL POLIOMYELITIS.
AB  - In two series of the experiments here recorded the monkey which had been
      repeatedly exposed to x-rays responded with typical acute poliomyelitis to an
      intracerebral inoculation of poliomyelitic virus filtrate, whereas the normal
      control receiving the same dose showed no symptoms. In another series the x-rayed
      animal came down with typical poliomyelitis after inoculation with three-fourths
      of the dose which was not infective for the control. It has been demonstrated
      that the x-rays diminished both the number of circulating lymphocytes and the
      resistance of the animal to the weak poliomyelitic virus. Whether the lowered
      resistance of the animals as the result of the treatment with x-rays is due to
      the reduction of circulating lymphocytes in each of the x-rayed monkeys is not
      determined in these experiments. However, the great reduction in lymphocytes in
      human cases and in monkeys during the acute stage of experimental poliomyelitis
      and the gradual return of the cells to their former numbers during recovery
      strongly suggest a definite relation between these cells and one factor of
      resistance in poliomyelitis. On the other hand, the reduction in resistance by x
      rays, while definite, is not sufficiently great to warrant the conclusion that we
      are dealing with major factors governing infection or non-infection. Another
      experiment in this paper deals with the survival of a subinfective dose of the
      virus in the normal monkey brain. A monkey receiving the subinfective dose of the
      virus was exposed to x-rays at 28 days, another at 15 days after injection, but
      neither animal showed symptoms of poliomyelitis. It is concluded that within this
      period the virus did not remain unchanged in the normal monkey brain. An attempt
      to reduce the immunity in a monkey acquired by an attack of experimental
      poliomyelitis was unsuccessful.

PMID- 19868298
TI  - THE ACTION OF CHLORINATED ANTISEPTICS ON BLOOD CLOT.
AB  - This work demonstrates that the chlorinated antiseptics have no power to
      penetrate blood clots and destroy bacteria therein contained. Correspondingly,
      blood clots may protect virulent bacteria for a long period of time and the
      organisms properly planted will be able to proliferate in a normal manner.

PMID- 19868299
TI  - THE TROPISTIC ACTION OF BLOOD VESSELS ON THE MIGRATION OF CHROMATOPHORES.
AB  - 1. The migrations of the chromatophores of the yolk sac of Fundulus heteroclitus
      seem to be chemotropic in character. 2. The determining factor seems to be either
      a high tension of oxygen or a comparatively low concentration of hydrogen ions.

PMID- 19868300
TI  - THE SOURCE OF THE LYMPHOCYTOSIS INDUCED BY MEANS OF HEAT.
AB  - A striking number of mitotic figures have been observed in the germinal center of
      the spleen and lymph glands during the regeneration of the cellular elements of
      these organs after the destructive effect of heat. This enhanced cell
      proliferation is interpreted as more than compensating for the degenerated cells,
      because of the subsequent enlargement of the organs. It has also been pointed out
      that the characteristic decrease in the number of lymphocytes immediately after
      the heat treatment is always accompanied by an extensive cell degeneration in
      spleen and lymph glands at the corresponding period. On this basis it seems
      evident that the pronounced lymphocytosis induced by means of heat treatment of
      the animal is due, at least in part, to the enhanced proliferative activity of
      germinal centers in the spleen and lymph glands, reacting to the destructive
      effect of heat upon lymphoid cells.

PMID- 19868301
TI  - THE LYMPHOCYTES IN NATURAL AND INDUCED RESISTANCE TO TRANSPLANTED CANCER : IV.
      EFFECT OF DRY HEAT ON RESISTANCE TO TRANSPLANTED CANCER IN MICE.
AB  - The marked and durable stimulation of the lymphoid elements induced by dry heat
      applied to the animal results in the establishment of a high degree of immunity
      to certain transplantable cancers in mice. This immunity is evident when the
      tumor used gives a low, as well as when it gives a high percentage of takes.

PMID- 19868302
TI  - EFFECT OF STIMULATION OF THE LYMPHOCYTES ON THE RATE OF GROWTH OF SPONTANEOUS
      TUMORS IN MICE.
AB  - Spontaneous cancers were removed from a series of mice by operation. The animals
      were then subjected to an exposure to dry heat at a temperature ranging from 55
      63 degrees C. for 5 minutes. Immediately afterwards a graft of the original tumor
      was returned. The mice so treated exhibited a marked increase in their resistance
      to the growth of the cancer graft, over 59 per cent remaining entirely free from
      a return of the cancer. In a control series in which no treatment was given 96
      per cent of the animals showed a return of the cancer.

PMID- 19868303
TI  - EXPERIMENTS ON THE ROLE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL
      TUBERCULOSIS IN MICE : III. EFFECT OF HEAT ON RESISTANCE TO TUBERCULOSIS.
AB  - Mice with high lymphocyte counts and increased activity of the lymphoid tissue
      induced by one exposure to intense dry heat exhibit a marked increase in the
      resistance to large doses of bovine tubercle bacilli as compared with that shown
      by control animals given a similar inoculation. This resistance, judged by the
      time of survival after inoculation, is increased from two- to threefold. The
      average length of life after inoculation for three groups of heated mice was 88,
      69, and 67 days respectively, while the control groups averaged 16, 29, and 28
      days respectively.

PMID- 19868304
TI  - EFFECT OF EXPOSURE TO THE SUN ON THE CIRCULATING LYMPHOCYTES IN MAN.
AB  - Chronic solar dermatitis was accompanied, in 25 of the 38 individuals studied, by
      an appreciable increase, percentage and absolute, in the number of circulating
      lymphocytes. In eight there was a definite decrease and in five no appreciable
      change after prolonged exposure to the rays of the summer sun. Of the thirteen
      subjects with no increase in blood lymphocytes, six failed to tan, three were so
      dark originally that to determine an increase was impossible, and five had an
      extremely high lymphocyte count at the first count. Blood counts on white persons
      living in the Philippines indicate that the blood lymphocytes are likewise
      increased after a prolonged period of residence in the tropical zone. Because of
      the parallelism between the tanning and the blood changes it seems probable that
      the lymphocytosis observed in the majority of instances, which is similar to the
      response of the blood of animals to small doses of the x-rays, is due to the
      effects of the ultra-violet rays contained in the solar spectrum.

PMID- 19868305
TI  - STUDIES ON X-RAY EFFECTS : I. DESTRUCTIVE ACTION ON BLOOD CELLS.
AB  - 1. X-rays in large doses affect the lymphocytes before any of the other
      circulating cells. 2. There is a sharp fall in the total number of circulating
      lymphocytes, which is complete 48 hours after x-ray treatment. 3. Following the
      immediate decrease in the circulating lymphocytes there is a primary rise,
      followed by another fall, which in turn is followed by a permanent rise of these
      cells to normal. 4. The effect of the x-rays on different species of animals
      varies considerably, but in those studied, cat, monkey, guinea pig, rabbit, rat,
      mouse, and pony, the selective action on the lymphocytes was in all instances
      apparent. 5. When several animals of the same species are given the same dose of
      x-rays, the effect on the circulating lymphocytes seems to be quantitatively
      parallel, when determined by blood counts. 6. The polymorphonuclear neutrophilic
      leucocytes, when affected at all, increase in number immediately after the
      administration of the x-rays and then tend to decrease below their normal level.
      This decrease is followed by a return to normal many days before the lymphocytes
      reach their original level. 7. The other cells of the blood follow the
      neutrophilic curve. 8. Percentage figures, as determined by differential blood
      counts, do not give an accurate indication of the effect of the x-rays. It is
      only when these are multiplied by the total white blood count that a figure,
      representing the total number of cells of the series per c. mm. of blood, is
      obtained, which varies to the stimulus in a constant manner, the variations being
      practically quantitative.

PMID- 19868306
TI  - STUDIES ON X-RAY EFFECTS : II. STIMULATIVE ACTION ON THE LYMPHOCYTES.
AB  - This study consists of blood counts on nine rabbits after an exposure to x-rays
      of a 7/8 inch spark-gap, milliamperage 25, distance from the target 8 inches, and
      time of exposure 20 minutes. In seven of the nine animals there resulted an
      increase of the circulating lymphocytes. In five of these the increase was marked
      and in two others definite but not striking. Of the two animals which showed no
      stimulation one showed marked fluctuation of counts both before and after x-rays
      and the other little or no change. The higher penetrating dose (6 inch spark-gap,
      milliamperage 5, distance from the target 10 inches, time 26 minutes and 57
      seconds) given to two animals produced no appreciable stimulation.

PMID- 19868307
TI  - STUDIES ON X-RAY EFFECTS : III. CHANGES IN THE LYMPHOID ORGANS AFTER SMALL DOSES
      OF X-RAYS.
AB  - 1. The small dose of x-rays applied to the rabbit has no appreciable destructive
      effect on the lymphoid tissue. 2. Indications of stimulation of the lymphoid
      tissue appear immediately after the treatment, become most pronounced in 2 (in
      lymph glands) to 4 (in the spleen) days, and persist, in a slight degree, up to
      the 14th day. 3. These facts suggest that the lymphocytosis induced by the small
      dose of x-rays is due to a primary stimulative effect upon the lymphoid tissue of
      the animal.

PMID- 19868308
TI  - STUDIES ON X-RAY EFFECTS : IV. DIRECT ACTION OF X-RAYS ON TRANSPLANTABLE CANCERS
      OF MICE.
AB  - These experiments indicate that the direct action of x-rays in more powerful
      doses than can be applied therapeutically is somewhat injurious to tumor cells,
      but by no means destroys them. Experiment 1 also indicates that the cancer cells
      establish a resistance to the x-rays after repeated doses. This harmonizes with
      the experience of clinicians who have succeeded in checking cancerous growths for
      some time but reach a point where no response can be effected by repeated doses.
      The rays of low penetration used in Experiment 2 are apparently more harmful to
      tumor cells than the penetrating rays used in Experiment 1.

PMID- 19868309
TI  - BLOOD COUNTS IN EXPERIMENTAL POLIOMYELITIS IN THE MONKEY.
AB  - Blood counts were made on six series of monkeys before and at various intervals
      after the injection of active poliomyelitic virus. From the data thus obtained
      the variations in the circulating white cells have been followed in the several
      stages of the disease (a) before injection, (b) during the incubation period, (c)
      during the acute stage, including the stage of prostration, and (d) during
      recovery. On account of experimental conditions not all the monkeys were observed
      during the four periods, so that averages of counts in several monkeys are used
      for comparison. Averages of 121 counts on 40 normal monkeys are recorded.
      Immediately following the injection of the virus the relative and actual numbers
      of lymphocytes are slightly diminished. In many cases the curve continues sharply
      downward. In others from the 4th to the 6th day there is an actual increase for a
      brief period to a point somewhat in excess of the original count. With the onset
      of symptoms a lymphocytic crisis takes place. The curve then continues slightly
      downward, while the polymorphonuclear neutrophilic leucocytes are relatively and
      actually increased at approximately the same time. During the stage of
      prostration the curve of the polymorphonuclear neutrophilic leucocytes returns to
      almost normal, while the lymphocytic curve continues slightly downward. With
      recovery the lymphocytes slowly return to normal after several weeks. There is no
      evidence of lymphocytic stimulation after recovery. Eosinophilic, basophilic,
      large mononuclear, and transitional leucocytes follow the depressions and
      stimulations exhibited by the neutrophilic cells of the same series. The results
      here recorded are consistent with the observations of Peabody, Draper, and Dochez
      on human cases. The increase in the total number of circulating lymphocytes after
      the lymphocytic crisis is coincident with the passing of the acute stage.
      Additional evidence is presented to indicate that Smillie produced atypical but
      definite poliomyelitis in the monkey with cultivated virus.

PMID- 19868310
TI  - BLOOD VOLUME IN WOUNDED SOLDIERS : I. BLOOD VOLUME AND RELATED BLOOD CHANGES
      AFTER HEMORRHAGE.
AB  - Blood volume tests made by the vital red method (Keith, Rowntree, and Geraghty)
      on patients after hemorrhage showed a marked reduction in the total blood bulk.
      Not uncommonly the blood volume was less than 60 per cent of the normal. The
      reduction after a certain point had been reached seemed to parallel the decrease
      in blood pressure. This relation of diminished blood volume to low pressure
      suggested a rough method of estimating blood volume from the change in blood
      pressure. By means of the blood volume and the hemoglobin per cent the actual
      amount of blood loss was determined. Cases of severe anemia showed a loss of as
      much as five-sixths of their total hemoglobin. Progressive changes in blood
      volume following hemorrhage were estimated in three ways: (1) repeated vital red
      tests; (2) calculation from changes in hemoglobin per cent produced by the
      injection of gum acacia; (3) calculation from changes in hemoglobin per cent
      following the dilution of the blood by the patient's own body fluids. The effects
      of the different methods of transfusion and of injection of gum acacia on blood
      volume were observed. No differences were apparent. It was found that transfusion
      and gum injections only partially restored the blood volume. Forced fluids by
      mouth were found to bring about its complete restoration in a comparatively short
      time. It was observed that the organism did not restore its blood volume beyond a
      certain point when a further increase in it would, by dilution, have brought the
      hemoglobin per cent to a very low figure. In such cases a further increase of the
      blood volume occurred only when the hemoglobin rose. In cases with a low
      hemoglobin per cent as the result of a restoration of the blood bulk an
      abnormally high blood pressure appeared, which continued until the hemoglobin per
      cent again increased. Accompanying the low blood pressure seen shortly after
      hemorrhage was a well marked difference in hemoglobin per cent between capillary
      and venous blood, with a relative concentration on the capillary side. As
      compensation occurred and blood pressure rose this difference lessened until the
      two readings were identical, indicating an even redistribution of the red blood
      cells. Reticulated red cell counts made in these cases showed that a marked bone
      marrow stimulation occurs after hemorrhage. However, except in the very anemic
      cases the degree of increased blood production seemed to depend largely on the
      restoration of the blood volume. The patients who were put on forced fluids, with
      consequent rapid restoration of blood volume, showed a much higher per cent of
      reticulated cells than those in whom no attempt was made to increase the amount
      of fluid in circulation.

PMID- 19868311
TI  - BLOOD VOLUME IN WOUNDED SOLDIERS : II. THE USE OF FORCED FLUIDS BY THE ALIMENTARY
      TRACT IN THE RESTORATION OF BLOOD VOLUME AFTER HEMORRHAGE.
AB  - Blood volume tests made on a number of soldiers recovering from hemorrhage have
      shown that in many instances dilution of the blood occurs very slowly. The
      principal reasons for this seem to be (a) an initial lack of reserve fluid of the
      tissues, and (b) the absence of any subsequent attempt by the body to make up
      this fluid deficiency. By putting such patients on a large fluid intake by mouth
      and rectum it has been found that their blood volume can be promptly and greatly
      increased. Hemorrhage cases transfused, yet still showing a low blood volume,
      were first treated in this way. Then the effect of forced fluids without
      transfusion was tried. Immediately after a hemorrhage, or as soon as the patient
      came under observation, he was given large quantities of water by mouth, and salt
      solution by rectum. Under such treatment the blood pressure soon began to show a
      progressive rise, the volume increased, and the red cells became more evenly
      redistributed, as shown by the relative hemoglobin percentages of the capillary
      and venous blood. These changes were often well marked after only 2 or 3 hours of
      the treatment. More than this, forcing fluids in cases where the amount of
      bleeding is difficult to estimate on account of the presence of a high hemoglobin
      percentage is of distinct value, since the dilution of the blood which results
      serves to show the extent of the hemorrhage through the drop in hemoglobin that
      it entails. In attempting to determine the condition of the patient after
      hemorrhage with a view to deciding the most suitable form of treatment, it is of
      much importance to learn the total blood loss-which is often not even indicated
      by the hemoglobin concentration of the remaining blood. With a total hemoglobin
      reduced to 25 per cent or under transfusion is needful. New blood is necessary,
      not only to supply more oxygen-carrying cells, but also because it actually
      enables the circulation to increase its volume. For, as has been pointed out in
      Paper I, the hemoglobin percentage must be above a certain point if a rapid
      restoration of the blood volume by means of the organism's own activities is to
      come about. With the total hemoglobin above 25 per cent the chief need is for
      increased blood volume, and if the patient's condition demands an immediate and
      large addition of circulating fluid, gum acacia solution should be given. If the
      condition is not so urgent, forced fluids by the alimentary tract are indicated.
      The blood volume can be considerably reduced and yet a normal blood pressure
      maintained. It is pointed out that the vasomotor mechanism which, has adapted
      itself to the diminished blood bulk may in any individual case be very near the
      margin of its compensatory power. Increased strain in such instances may cause a
      failure of this mechanism with a resulting fall in blood pressure. The beneficial
      results of forced fluids after secondary hemorrhage suggest the value of the
      early use of fluids by the alimentary tract in cases of primary hemorrhage.

PMID- 19868312
TI  - THE INFLUENCE OF ETHER ANESTHESIA, OF HEMORRHAGE, AND OF PLETHORA FROM
      TRANSFUSION ON THE PRESSOR EFFECT OF MINUTE QUANTITIES OF EPINEPHRINE.
AB  - Ether anesthesia has a marked influence in diminishing the pressor response to
      minute amounts of epinephrine injected directly into the circulation. Hemorrhage
      also acts to lessen or abolish the response, and to a degree directly
      proportional to the lowering of the blood pressure it causes. In the
      exsanguinated animal an amount of epinephrine three or four times that sufficient
      to produce a pressure rise of 10 to 15 mm. of mercury under normal conditions,
      may be entirely without effect. The response to large doses, on the other hand,
      is uninfluenced by ether or hemorrhage. The facts stated have a practical bearing
      not only on the employment of epinephrine to tide over collapse but on its
      possible utilization in the future to raise a low blood pressure to the normal
      height and maintain it during a considerable period. For the amount of
      epinephrine which under normal conditions will suffice to bring up the blood
      pressure may have little or no effect on an etherized individual or on one who
      has lost blood. The same difficulty will doubtless be encountered under other
      conditions. In animals rendered plethoric by transfusion the response to small
      doses of epinephrine lessens in proportion as the blood pressure is increased by
      the plethora.

PMID- 19868313
TI  - BACILLUS EGENS. A NEW PATHOGENIC ANAEROBE.

PMID- 19868314
TI  - SPIROCHAETA HEBDOMADIS, THE CAUSATIVE AGENT OF SEVEN DAY FEVER (NANUKAYAMI) :
      SECOND PAPER.
AB  - 1. Spirochata hebdomadis is always present in seven day fever and can be
      confirmed by animal experiments with guinea pigs of light weight. 2. The
      causative agent of this disease can also be found in film preparations of the
      blood of patients, though it is not present in large numbers. 3. Spirochaeta
      hebdomadis is discharged in the urine of patients having seven day fever. The
      number of spirochetes in the urine is great during convalescence. 4. Seven day
      fever is a disease found not only in the Prefecture of Fukuoka, but in many other
      districts of Japan as well.

PMID- 19868315
TI  - THE USE OF THE FINAL HYDROGEN ION CONCENTRATION IN DIFFERENTIATION OF
      STREPTOCOCCUS HAEMOLYTICUS OF HUMAN AND BOVINE TYPES.
AB  - 1. Under the conditions of these experiments, there appears to be a distinct and
      constant difference in the final hydrogen ion concentration of Streptococcus
      haemolyticus from human and bovine sources. 2. Of 124 strains of Streptococcus
      haemolyticus from known human origin, 116 reached a final hydrogen ion
      concentration of from pH 5.0 to 5.3. Only 8 reached a pH more acid than 5.0 and
      none more acid than pH 4.8. 3. Of 45 strains of Streptococcus haemolyticus from
      bovine sources, including 26 strains isolated from milk and the udder of cows,
      and 19 from cream cheese, 40 reached a final hydrogen ion concentration of pH 4.3
      to 4.5. Of the remaining 5 which reached a pH of 5.0 to 5.2, two were of known
      human type and three of uncertain diagnosis. 4. A rapid and practical application
      of this method is proposed as a presumptive test in the differentiation of human
      and bovine types of Streptococcus haemolyticus.

PMID- 19868316
TI  - THE TEMPERATURE OF ACUTELY INFLAMED PERIPHERAL TISSUE.
AB  - The experiments set forth here establish the fact that the heat of the inflamed
      part has its origin primarily in the local biochemical activity of the cellular
      elements which participate in the inflammatory process. The inflammatory
      hyperemia, instead of being the necessary and constant source of the inflammation
      must be considered a natural physiological compensation for the abnormal local
      calorification. The rapid circulation of the blood in the inflamed part tends to
      moderate the increase in local temperature and to equalize the temperature with
      that of other parts of the body.

PMID- 19868317
TI  - THE OCCURRENCE OF BACILLUS INFLUENZAE IN THROATS AND SALIVA.
AB  - 1. Oleate hemoglobin agar is a good selective culture medium for Bacillus
      influenzae. 2. Bacillus influenzae has been cultivated from the mouth of 93 per
      cent of cases of influenza and bronchopneumonia. 3. Bacillus influenzae was
      present at the time of this study in the mouths of 43 per cent of normal
      individuals. 4. The types of pneumococci found associated with the complicating
      bronchopneumonias of influenza are the types which are usually found in normal
      mouths.

PMID- 19868318
TI  - THE DETERMINATION OF THE LENGTH OF LIFE OF TRANSFUSED BLOOD CORPUSCLES IN MAN.
AB  - 1. It is possible in mixtures of corpuscles of different groups to separate the
      corpuscles practically quantitatively by treating with a serum that agglutinates
      the corpuscles of one kind, leaving the others unagglutinated. 2. After a
      recipient has been transfused with blood of a group other than his own, specimens
      of his blood treated with a serum that will agglutinate his own corpuscles but
      not the transfused corpuscles show unagglutinated corpuscles in large numbers. 3.
      These unagglutinated corpuscles which appear in the recipien's blood after such a
      transfusion are the transfused corpuscles and their count is a quantitative
      indicator of the amount of transfused blood still in the recipient's circulation.
      4. The life of the transfused corpuscle is long; it has been found to extend for
      30 days and more. The beneficial results of transfusion are without doubt not due
      primarily to a stimulating effect on the bone marrow, but, it is reasonable to
      assume, to the functioning of the transfused blood corpuscles.

PMID- 19868319
TI  - EXPERIMENTS ON THE PRODUCTION OF SPECIFIC ANTISERA FOR INFECTIONS OF UNKNOWN
      CAUSE : I. TYPE EXPERIMENTS WITH KNOWN ANTIGENS-A BACTERIAL HEMOTOXIN
      (MEGATHERIOLYSIN), THE PNEUMOCOCCUS, AND POLIOMYELITIC VIRUS.
AB  - Attempts to produce antisera in animals to combat specific infections are usually
      deferred until the cause of the infection has been isolated and grown in pure
      culture to furnish antigen. It has seemed to us that the fulfillment of these
      conditions might in some cases be rendered unnecessary through the use of
      infected tissue itself as an antigen, combined with selective absorption of the
      antiserum to rid it of elements injurious to the species furnishing the tissue.
      In order to test this possibility type experiments have been carried out with
      immune sera effective against known antigens of three different sorts: 1. Sera
      resulting from the injection of rabbits and a goat with normal guinea pig tissues
      and a bacterial hemotoxin, the megatheriolysin described by Todd, which hemolyzes
      guinea pig cells. The sera possessed strong antitoxins for the megatheriolysin
      but were fatal to guinea pigs. By the method of selective absorption they were
      rendered innocuous to these animals and were successfully used to protect them
      from lethal doses of the megatheriolysin. 2. Anti-rabbit dog sera containing
      antibodies protective against pneumococcus infection. Such sera, subjected to
      repeated absorption with rabbit red cells, proved capable of protecting mice from
      pneumococcus infection in exactly the same degree as the unexhausted serum; that
      is to say, they protected against 100 times the dose of pneurnococci that was
      fatal with normal dog serum. 3. The serum of a monkey recovered from
      poliomyelitis and repeatedly injected with human red cells and extract of
      placental tissue. This serum, after selective absorption with human red cells,
      protected a monkey against an intracerebral dose of poliomyelitic virus fatal to
      eight other monkeys given it with normal monkey or human serum. The results in
      these instances, purposely chosen for their simplicity, would seem to indicate
      for the absorption method some usefulness in the study of immunity to infections
      of unknown cause. In Part II of our paper the method is applied to one such
      infection; namely, a sarcoma of the fowl engendered by a filterable agent. A
      general discussion will be found in connection with this portion of the work.

PMID- 19868320
TI  - EXPERIMENTS ON THE PRODUCTION OF SPECIFIC ANTISERA FOR INFECTIONS OF UNKNOWN
      CAUSE : II. THE PRODUCTION OF A SERUM EFFECTIVE AGAINST THE AGENT CAUSING A
      CHICKEN SARCOMA.
AB  - By the method of selective absorption with tissue, protective serum antibodies
      have been demonstrated in the case of an infection of unknown cause; namely, a
      chicken sarcoma transmitted by a filterable agent. Geese were repeatedly injected
      with the finely ground sarcoma and with blood from fowls moribund of it; and
      their sera acquired the power to prevent the tumor-producing agent from causing
      growths. That this was not due to antibodies elicited by the chicken tissue as
      such was shown by exhaustion of the goose sera with chicken red cells, a step
      which had not the least effect on the tumor-preventing power, and also by
      experiments with rabbits immunized as were the geese. These animals developed
      strong chicken antibodies in their sera which failed nevertheless to affect the
      tumor-producing agent. Serum immunity to the chicken sarcoma is weak at best; and
      in the case of some other infections of unknown cause, more striking results may
      be anticipated from the method of selective absorption. It is even conceivable
      that by its means sera of therapeutic usefulness may become available. But much
      remains to be settled as regards the dangers of exhausted sera and the
      limitations of the method. Fortunately there exists an immediate field for the
      latter in laboratory studies on the nature of immunity to infections of which the
      cause has not been recognized.

PMID- 19868321
TI  - THE EFFECT OF CARBON DIOXIDE IN THE CULTIVATION OF THE MENINGOCOCCUS.
AB  - The meningococcus is not a "microaerophile." It grows equally well in atmospheres
      containing from 15 to 40 per cent oxygen. If small amounts of carbon dioxide
      affect the growth of the meningococcus on an artificial medium it is by changing
      the reaction of the medium, not by slightly reducing the oxygen tension of the
      surrounding air. The fallibility of titrating the total acidity of a medium is
      again clearly demonstrated. A reaction favorable to the meningococcus cannot be
      determined from the total titratable acidity but depends solely upon the hydrogen
      ion concentration of the medium. The optimum for the meningococcus is
      approximately at pH 7.4. The value of a moist chamber in the cultivation of the
      meningococcus is shown by unusually luxuriant growth when other conditions are
      also favorable.

PMID- 19868322
TI  - CICATRIZATION OF WOUNDS : X. A GENERAL EQUATION FOR THE LAW OF CICATRIZATION OF
      SURFACE WOUNDS.
AB  - 1. The law of cicatrization, of surface wounds may be expressed by an exponential
      formula in which the two coefficients may be determined. 2. A simple relation
      exists between these coefficients and the index, i, of cicatrization, previously
      established in function of the age of the patient and of the area of the wound.
      3. The proposed equation with a simplified exponent, reduced to a single
      coefficient, expresses satisfactorily the phenomenon of contraction.

PMID- 19868323
TI  - OBSERVATIONS ON THE WASSERMANN REACTION : A COMPARISON OF THE NEW SYSTEM OF
      NOGUCHI WITH THAT USING CHOLESTEROLIZED ANTIGEN ACCORDING TO MCINTOSH AND FILDES.
AB  - The Wassermann reaction carried out according to the method of McIntosh and
      Fildes, with cholesterolized antigen and with certain allowances for the presence
      of native anti-sheep amboceptor; leads to about the same result as when it is
      done according to the recent proposal of Noguchi, with the native human
      complement and acetone-insoluble lipoids as antigen. The differences are such as
      to suggest that from the point of view of diagnosis the Noguchi method is the
      more conservative but that there is definite advantage in using two metnods as
      distinct in origin of materials as these, partly for the purpose of control and
      partly in the hope of acquiring new information of importance. As a measure of
      control of treatment the cholesterol antigen appears to us to be the more
      valuable. The Wassermann reaction alone, by whatever method it may be done, can
      only be used in the diagnosis of syphilis in conjunction with presumption based
      on other grounds. That it fails to appear in a considerable percentage of
      syphilitics is well known. That the reaction is positive in other conditions is
      not so generally recognized. Fresh instances of this in certain febrile cases are
      here recorded.

PMID- 19868324
TI  - MIGRATION OF PARASITES AS THE CAUSE OF ANEMIA IN AESTIVO-AUTUMNAL MALARIAL
      INFECTIONS.
AB  - The anemia in malarial infections is explained by the fact that each parasite
      destroys several red corpuscles. Reduction of hemoglobin out of proportion to the
      loss of red corpuscles is explained by the fact that there is always a partial
      loss of hemoglobin in certain of the surviving corpuscles due to parasitic
      action. Migration of parasites occurs in all aestivo-autumnal infections. If one
      wishes to observe, migrations, it will save time to study the heavy infections.
      Free parasites have been frequently noted by many observers, who have failed to
      interpret properly their presence in the blood.

PMID- 19868325
TI  - THE FUNCTIONAL VALUE OF NEWLY FORMED CONNECTIVE TISSUE.
AB  - 1. A method has been revived which enables the connective tissue factor in wound
      healing to be studied quantitatively. 2. It has been found that the functional
      value of connective tissue formed in response to traumatism as represented by its
      tensile strength varies widely in different animals. 3. It is suggested that the
      method may find application in the study of extraneous influences which may
      affect wound healing either through local or systemic application. 4. It has been
      determined that there is no parallelism between an active connective tissue
      response to traumatism and natural resistance to inoculation tuberculosis in the
      rabbit.

PMID- 19868326
TI  - PERSISTENCE OF THE VIRUS OF POLIOMYELITIS IN THE NASOPHARYNX.
AB  - The virus of poliomyelitis occurs in the nasopharynx of man and monkeys. In man
      it has been detected by the inoculation test in washings from acute cases, rarely
      in similar washings from healthy contacts, in the nasopharyngeal tissues obtained
      from fatal cases in the 1st week of infection, but rarely, if ever, from
      nasopharyngeal tissues removed surgically at later periods in the course of the
      disease. In monkeys, also, the virus has been detected in the secretions from
      acute experimental infections, in the nasopharyngeal tissues derived from early
      cases, and rarely from cases several weeks or months after recovery from the
      acute symptoms. The inoculation of tonsils and adenoids obtained from cases of
      undoubted poliomyelitis either yielded definite results in the form of typical
      paralysis and histological lesions in the central nervous organs of the monkeys
      injected, or no symptoms or lesions which could be confounded with poliomyelitis.
      The indefinite symptoms and atypical lesions described in a certain class of
      inoculated animals by Kling, Pettersson, and Wernstedt were not encountered in
      our experiments. The deduction from the experiments reported is to the effect
      that the virus is regularly present in the nasopharynx in cases of poliomyelitis
      in the first days of illness, and especially in fatal cases; that it diminishes
      relatively quickly as the disease progresses, except in rare instances; and that
      it is unusual for a carrier state to be developed. Hence the period of greatest
      infectivity of patients would appear to be early in the disease, which is
      probably the time at which communication of the virus from person to person takes
      place. Available evidence proves that healthy carriers of the virus occur. We do
      not, however, possess data which indicate the frequency with which carriage
      arises. The fact that even after a severe and wide epidemic, such as occurred in
      the United States in 1916, the disease may virtually disappear within 2 or 3
      years, points to the probability that enduring carriers of the active virus,
      whether healthy or chronic, are of exceptional occurrence.

PMID- 19868327
TI  - I. RENAL FUNCTION INFLUENCED BY INTESTINAL OBSTRUCTION.
AB  - Associated with the intoxication of intestinal obstruction there exists a
      definite impairment of the excretory function of the kidneys. The degree of
      functional depression corresponds roughly with the intensity of the clinical
      intoxication. The decrease in the urea ratio and in the capacity of the kidneys
      to excrete sodium chloride is more marked than is the percentage decrease of
      phenolsulfonephthalein elimination. The great increase in the non-protein
      nitrogen of the blood usually observed in acute intestinal obstruction, which has
      hitherto been explained as being due entirely to an increased rate of protein
      catabolism, is due in part to retention of the products released from the injured
      cell protein. It is probable that the impaired renal function is due to direct
      action of the toxic substances upon the renal epithelium. The actual
      demonstration of this renal injury is perhaps the strongest evidence so far
      obtained to prove the presence of an actual toxic substance in the blood during
      intestinal obstruction. This obscure disability of the kidneys during the height
      of the intoxication of acute ileus should always be considered in the clinical
      management of this condition. It may also serve as a guide to indicate the degree
      of intoxication.

PMID- 19868328
TI  - II. RENAL FUNCTION INFLUENCED BY PROTEOSE INTOXICATION.
AB  - The injection of the toxic proteose obtained from the contents of the obstructed
      small intestine causes a definite impairment of the eliminative function of the
      kidneys as shown by a decreased capacity to excrete urea, sodium chloride, and
      phenolsulfonephthalein. This involvement of the renal function is similar to that
      shown by the preceding report (1) to accompany the intoxication of intestinal
      obstruction. The observed depression of function is readily demonstrable even
      when large amounts of fluid and urea, dye, or salt are injected directly into the
      blood stream. There is in all probability a temporary injury of the kidney cells,
      since the most important extrarenal factors have been largely eliminated in the
      above experiments. There is no appreciable impairment of the renal function
      following the injection of a number of other proteose preparations from a variety
      of sources. This study affords new evidence in favor of the view that the
      function of an organ can be profoundly disturbed for a time without any
      demonstrable anatomical lesions. The repair of this type of injury promptly
      follows the disappearance of the intoxication and is functionally and
      anatomically perfect.

PMID- 19868329
TI  - EFFECT OF BILE ON THE CLOTTING TIME OF BLOOD.
AB  - 1. Within certain limits the clotting time of blood, of blood plasma, and of
      solutions of fibrin to which bile salts have been added, is proportional to the
      quantity of bile present. 2. The bile interferes with the conversion of
      fibrinogen into fibrin and not with the formation of thrombin.

PMID- 19868330
TI  - A CHARACTERISTIC LOCALIZATION OF BACILLUS ABORTUS IN THE BOVINE FETAL MEMBRANES.
AB  - The significance of this invasion of the chorionic epithelium from the standpoint
      of pathogene'sis cannot be properly evaluated until a more complete history of
      the successive localizations of Bacillus abortus has been obtained. It is safe to
      assume that this particular cell parasitism is but one of a series of
      localizations and centers of multiplication in the fetal membranes although
      evidence points to it as perhaps the earliest stage in which the organism gains
      by rapid, unchecked multiplication a considerable advantage over the host. The
      local destruction of an epithelial covering by an infectious agent when other
      miscellaneous infectious agents are absent may or may not be of much importance,
      for it would depend on the regenerative activity of the epithelium, the tendency
      to the gathering of injurious transudates, and the toxic substances associated
      with the bacilli. It is probable that localizations also occur in the walls of
      the blood vessels of the chorion. Thus far only one case of this kind has been
      observed. The fusiform connective tissue cells of the adventitious coat of a
      blood vessel 0.8 mm. in diameter were completely replaced by clumps of minute
      bacilli. Since there is usually a slight perivascular cell infiltration in the
      diseased placenta this localization may be largely responsible for the
      circulatory disturbances which lead to death of the fetus. The case referred to
      may be but a greatly exaggerated illustration of the action of Bacillus abortus
      in the walls of the blood vessels where they are too few in number at any one
      time to be identified. It is known, that in the guinea pig disease with
      pronounced lesions Bacillus abortus is demonstrated only with great difficulty
      because of its scarcity. The more or less specific localization and
      multiplication of bacteria within cells not having phagocytic functions have thus
      far been demonstrated in leprosy, syphilis, and in a disease of mice recently
      described by Tyzzer, who found an active invasion of both liver cells and
      intestinal epithelium by a bacillus. In cells to which phagocytic powers have
      been ascribed the specific localization of certain bacteria is well known. Thus
      tubercle bacilli occur within the endothelial cells of the tubercle. Leprosy
      bacilli have been found within a variety of cell groups. Mouse septicemia bacilli
      occur regularly within certain phagocytic cells of the blood. Recently bacteria
      have been found attached to the cilia of the respiratory tract in pertussis by
      Mallory and Hornor, in a form of guinea pig pneumonia by the writer. Actual
      occupation of epithelial cells followed by active multiplication of the invaders
      and destruction of the cell has, however, been frequently demonstrated for the
      sporozoa. That it may occur more often among bacteria is highly probable.
      Rapidity of multiplication and cell destruction or invisibility or both may stand
      in the way of a satisfactory demonstration.

PMID- 19868331
TI  - RESULTS OF PROPHYLACTIC VACCINATION AGAINST PNEUMONIA AT CAMP WHEELER.
AB  - 1. 13,460 men, or about 80 per cent of the entire camp strength, were vaccinated
      against pneumonia with pneumococcus lipovaccine. 2. The dosage employed in all
      cases was 1 cc. of the lipovaccine containing approximately 10 billion each of
      Pneumococcus Types I, II, and III. 3. Both the local and general reactions
      produced by the vaccine were usually mild. Only 0.7 per cent of those who
      received the vaccine were sufficiently affected to need hospital care. None of
      these was seriously ill, and a majority of them returned to duty on the 2nd or
      3rd day after admission. 4. Most of the troops inoculated were under observation
      for 2 or 3 months after vaccination. During this period there were 32 cases of
      Pneumococcus Type I, II, and III pneumonia among the vaccinated four-fifths of
      camp, and 42 cases of pneumonia of these types among the unvaccinated one-fifth
      of camp. If, however, all cases of pneumonia that developed within 1 week after
      vaccination are excluded from the vaccinated group, there remain only 8 cases of
      pneumonia produced by fixed types, and these were all secondary to severe attacks
      of influenza. This exclusion is justified by the fact that protective bodies do
      not begin to appear in the serum until the 8th day after injection of
      pneumococcus lipovaccine. 5. There is no evidence whatever that pneumococcus
      vaccine predisposes the individual even temporarily toward either pneumococcus or
      streptococcus pneumonia. 6. The weekly incidence rate for pneumonia (all types)
      among the vaccinated troops was conspicuously lower than that for the
      unvaccinated troops. 7. The pneumonia incidence rate per 1,000 men during the
      period of the experiment was twice as high for unvaccinated recruits as for
      vaccinated recruits, and nearly seven times as high for unvaccinated seasoned men
      as for vaccinated seasoned men. 8. Influenza causes a marked reduction in
      resistance to pneumonia even among vaccinated men. Of the 155 cases of pneumonia
      (all types) developing 1 week or more after vaccination, 133 were secondary to
      influenza. 9. The death rate for 155 cases of pneumonia (all types) that
      developed among vaccinated men 1 week or more after vaccination was only 12.2 per
      cent, whereas the death rate for 327 cases of all types that occurred among
      unvaccinated troops was 22.3 per cent. The death rate for primary pneumonia among
      vaccinated troops was 11.9 per cent. Among unvaccinated, it was 31.8 per cent,
      almost three times as great. On the other hand, the mortality rate in pneumonia
      secondary to influenza is about the same for the vaccinated and unvaccinated
      groups. 10. In conclusion, it must be admitted that the results of pneurnococcus
      vaccination at Camp Wheeler have not been so striking as those obtained at Camp
      Upton in 1918, largely on account of the influenza epidemic; but, although
      influenza obscured to some extent the effect of pneumococcus vaccination at Camp
      Wheeler, the results are sufficiently encouraging to justify its further
      application in civil as well as in military life.

PMID- 19868332
TI  - THE ACTION OF STROPHANTHIN ON THE LIVING CAT'S HEART.
AB  - 1. Cats vary considerably in their susceptibility to strophanthin and in the
      extent of the difference between the minimum lethal dose and the minimum toxic
      dose. 2. The amount of strophanthin necessary to produce a toxic effect in a
      given cat is independent of the speed of administration to a period of 4 hours.
      An improvement in the clinical administration of the drug is thereby indicated.
      3. A theory of the action of strophanthin is formulated which reconciles the
      results which point to the importance of the total amount taken up by the heart
      with those inidicate that the concentration of the drug is the determining
      factor.

PMID- 19868333
TI  - A FUNCTIONAL AND PATHOLOGICAL STUDY OF THE CHRONIC NEPHROPATHY INDUCED IN THE DOG
      BY URANIUM NITRATE.
AB  - 1. Uranium nitrate is relatively more toxic for old animals than for young
      animals. 2. This relative toxicity is not only expressed in the old animals by a
      greater functional disturbance of the kidney, but is also shown by an inability
      on the part of these animals to repair the kidney injury and reestablish its
      functional capacity. 3. The intoxication in younger animals has been followed by
      a repair of the renal injury and a partial restoration of kidney function. 4. In
      these animals the processes of repair lead to the development of a chronic
      diffuse type of nephropathy in which the acid-base equilibrium of the blood may
      be maintained at the point of normality. In these animals renal functional tests
      indicate the presence of severe kidney injury.

PMID- 19868334
TI  - THE AGGLUTINATION REACTIONS OF THE MORGAN BACILLUS NO. 1.
AB  - The study of the cultural and agglutinating reactions of seventeen strains of
      Morgan bacilli is reported. The cultures were obtained from different sources.
      Culturally all the strains were identical. Antigenically they were highly
      diversified. The sera produced against some strains have marked agglutinating
      power for other strains, but absorption tests showed that the cross
      agglutinations were often due to group agglutinins. While no conclusion can be
      drawn regarding the pathogenic significance of this bacillus, the wide
      diversities of antigenic properties raise the question as to the specific
      relationship of the various cultures met with as well as their relation to a
      definite class of pathological processes in man.

PMID- 19868335
TI  - EDEMA OF THE LUNGS AS A CAUSE OF DEATH.

PMID- 19868336
TI  - ETIOLOGY OF YELLOW FEVER : I. SYMPTOMATOLOGY AND PATHOLOGICAL FINDINGS OF THE
      YELLOW FEVER PREVALENT IN GUAYAQUIL.
AB  - The clinical and pathological features of the yellow fever prevalent in Guayaquil
      conform with those described by other investigators of this disease as it has
      occurred elsewhere, both epidemically and endemically.

PMID- 19868337
TI  - ETIOLOGY OF YELLOW FEVER : II. TRANSMISSION EXPERIMENTS ON YELLOW FEVER.
AB  - By injecting into guinea pigs the blood of yellow fever cases occurring in
      Guayaquil a group of symptoms and lesions closely resembling those observed in
      human yellow fever were induced in a limited number of instances. Of 74 guinea
      pigs inoculated with specimens of blood from 27 cases of yellow fever, 8,
      representing 6 cases, came down with the symptoms; namely, a marked rise of
      temperature after a period of incubation averaging 3 to 6 days, with simultaneous
      suffusion of the capillaries, particularly of the conjunctivaes and soles, then
      preliminary hyperleucocytosis followed by progressive leucopenia, the early
      appearance of albumin and casts in the urine, which gradually diminishes in
      volume as the disease progresses. The fever lasts only a few days, rapidly
      dropping first to the normal and then usually to subnormal. At this period
      jaundice manifests itself in varying degrees of intensity, first in the scleras,
      then in the skin and the urine. Hemorrhages from the nasal or gingival mucosa or
      anus have been observed to occur during this period. Autopsies reveal deep
      jaundice throughout the entire tissue. The liver is fatty and yellow, the kidney
      hyperemic, and often swollen and hemorrhagic. Hemorrhagic spots were almost
      always found in the lungs and gastrointestinal mucosa. Guinea pigs are usually
      rather sensitive to the infection, though many appeared to be somewhat resistant
      and some even refractory. The injection of the yellow fever blood into ringtail
      monkeys, rabbits, cats, guatusas, weasels, and sloths among the mammalians, and
      pigeons, ground-doves, bluebirds, mantas, blackbirds, parrakeets, reedbirds,
      blancos, and toucans among the birds, gave negative results. In the blood, liver,
      and kidneys of the guinea pigs experimentally infected with the blood of yellow
      fever patients a minute organism was demonstrated which closely resembles in
      morphology the causative agent of infectious jaundice (Leptospira
      icterohamorrhagiae). The leptospira transmitted from yellow fever cases to guinea
      pigs was found to induce similar symptoms and lesions upon further passage into
      normal guinea pigs. The leptospira obtained from cases of yellow fever has been
      givern the provisional name of Leptospira icteroides.

PMID- 19868338
TI  - ETIOLOGY OF YELLOW FEVER : III. SYMPTOMATOLOGY AND PATHOLOGICAL FINDINGS IN
      ANIMALS EXPERIMENTALLY INFECTED.
AB  - Studies are reported on the type of disease induced in guinea pigs, dogs, and
      monkeys by inoculating them (1) with the blood or organ emulsions of guinea pigs
      or other susceptible animals experimentally infected with Leptospira icteroides,
      and (2) with a pure culture of the organism. Particular attention has been given
      in these experiments to the clinical features of the experimental infection in
      the various animals and to the pathological changes resulting from the infection.
      The symptoms and pathological lesions induced in guinea pigs are much more
      pronounced than those observed in dogs or marmosets. The period of incubation is
      nearly the same in all three species, 72 to 96 hours with intraperitoneal or
      subcutaneous inoculation, and a day or more longer when the infection is induced
      percutaneously or per os. The febrile reaction in the guinea pig and marmoset is
      about the same; in the dog there is less fever. The amount of albumin, casts, and
      bile pigments in the urine is more abundant in the guinea pig and marmoset than
      in the dog, and these animals also appear on the whole to become more intensely
      icteric. The black or bilious vomit, however, though occurring frequently in dogs
      during life, is observed in the guinea pig and marmoset at autopsy. The
      hemorrhagic diathesis is most pronounced in guinea pigs, less so in marmosets,
      and least in dogs. In dogs) for example, subcutaneous hemorrhages almost never
      occur, and the lungs usually show only a few minute ecchymoses. The pleurse,
      pericardium, and other serous surfaces of the thorax and abdomen remain free from
      ecchymoses, which, however, with hyperemia, are very marked along the
      gastrointestinal tract. The symptoms and lesions observed in animals
      experimentally infected with Leptospira icteroides closely parallel those of
      human yellow fever. The pathological changes occurring in human cases of yellow
      fever are similar to those induced by inoculation in guinea pigs and marmosets
      and in respect to their intensity stand intermediate between those arising in the
      two animals mentioned.

PMID- 19868339
TI  - THE PASSAGE OF MENINGOCOCCIC AGGLUTININS FROM THE BLOOD TO THE SPINAL FLUID OF
      THE MONKEY.
AB  - Agglutinins for the meningococcus were not found in the spinal fluid of normal
      monkeys which had received antimeningococcic serum intravenously. The intraspinal
      injection of isotonic salt solution, normal horse serum, or a culture of living
      meningococci allows agglutinins for the meningococcus to pass from the blood to
      the spinal fluid of the passively immunized monkey; and the rate of the passage
      is affected by the severity of the inflammation induced in the meninges. The
      rates of elimination from the blood and spinal canal of meningococcic antibodies,
      as shown by the agglutination reaction, were compared in monkeys treated with
      immune serum (a) intraspinally, (b) intravenously, and (c) intraspinally and
      intravenously in combination. (a) When immune serum is given intraspinally the
      agglutinins are very much diminished after 8 hours and practically disappear at
      12 hours. They appear in the blood at the 4th hour after injection and quickly
      diminish. (b) After intravenous injection of immune serum, when the meninges are
      inflamed, agglutinins appear in the spinal fluid in small amounts in about 12
      hours and increase to the 25th hour. More than one-half of the agglutinins
      disappear from the blood within 8 hours and remain in low concentration at 25
      hours. (c) After combined intraspinal and intravenous injection the agglutinins
      remain in higher concentration in the spinal fluid and for a longer time than by
      method (a) or (b). The curve descends after 12 hours, and agglutinins are present
      at 25 hours. They remain in maximum concentration in the blood for 25 hours.

PMID- 19868340
TI  - EXPERIMENTS ON THE MODE OF INFECTION IN EPIDEMIC MENINGITIS.
AB  - The lower monkeys as represented by Macacus rhesus are resistant to a high degree
      to infection with cultures of the meningococcus introduced into the general
      blood. The lower monkeys are less resistant to infection when the meningococcus
      cultures are injected directly into the subarachnoid space by lumbar puncture.
      Relatively virulent cultures, which have been passed through several monkeys,
      acquire the power of surviving in the circulating blood of the monkeys for a
      maximum period of about 72 hours. Nothing has, however, been observed to indicate
      that the injected meningococci actually multiply in the blood. It has not been
      found possible to direct the meningococci circulating in the blood into the
      cerebrospinal meninges of monkeys. In this effort an aseptic meningitis was
      induced by injecting horse serum, saline solution, or protargol into the
      subarachnoid space preceding the introduction of the meningococci into the blood.
      In rabbits the meningococci were able to pass into the spinal fluid from the
      blood when a physical break in the continuity was made; however, under the
      conditions of chemical inflammation of the meninges the rabbit reacted just as
      the monkeys, and the organisms did not pass. Because of the high insusceptibility
      of the monkey to infection with meningococcus, it is not believed that the
      experiments throw any new light on the mode of invasion of the body in man by
      that microorganism. The experiments do not lend any support to the notion that an
      intraspinal injection of the antimeningococcus serum, early in the course of
      invasion of meningococcus in man, and possibly at a period at which the meninges
      do not yet show evidences of inflammation, favors its diversion from the blood
      stream into the subarachnoid space.

PMID- 19868341
TI  - ETIOLOGY OF YELLOW FEVER : IV. THE ACQUIRED IMMUNITY OF GUINEA PIGS AGAINST
      LEPTOSPIRA ICTEROIDES AFTER THE INOCULATION OF BLOOD OF YELLOW FEVER PATIENTS.
AB  - The majority of guinea pigs inoculated with the blood of yellow fever patients
      escaped a fatal infection. There were a number of instances in which the
      inoculation of yellow fever blood induced in these animals a temporary febrile
      reaction on the 4th or 5th day, followed in some cases by slight jaundice, but
      with a rapid return to normal. Most of these guinea pigs when later inoculated
      with an organ emulsion of a passage strain of Leptospira icteroides resisted the
      infection. On the other hand, the animals which had previously been inoculated
      with the blood of malaria patients or normal guinea pigs died of the typical
      experimental infection after being inoculated with the infectious organ emulsion.
      It appears from the results just described that a number of nonfatal, mild, or
      abortive infections follow the inoculation of blood of yellow fever patients into
      guinea pigs. The fact that such animals manifested refractoriness to a subsequent
      attempt to infect with a highly virulent passage strain of Leptospira icteroides
      is an indication, judging from the reciprocal immunity reaction, that they
      actually passed through an infection with the same organism, or a strain closely
      related to it, as that which was used for the second infection experiment.

PMID- 19868342
TI  - ETIOLOGY OF YELLOW FEVER : VI. CULTIVATION, MORPHOLOGY, VIRULENCE, AND BIOLOGICAL
      PROPERTIES OF LEPTOSPIRA ICTEROIDES.
AB  - By the employment of methods designed to promote the growth both of aerobic and
      anaerobic organisms, particularly those belonging to the class of spirochetes, it
      was possible to obtain a pure culture of a delicate organism, the morphological
      features of which place it in the genus Leptospira. On three occasions, that is,
      from three out of eleven cases of yellow fever, the organism was directly
      cultivated. These three strains were found to induce the characteristic symptoms
      and lesions when tested on guinea pigs. The organism was designated Leptospira
      icteroides. Leptospira icteroides was also obtained in pure culture from the
      blood of guinea pigs which succumbed to infection after being inoculated with the
      blood or organ emulsions from patients suffering from yellow fever. These
      cultures also proved to be virulent when tested on susceptible animals. The
      morphological characteristics and certain biological properties of the organism
      were considered in detail. It is invisible under translucent illumination and is
      difficult to stain by most aniline dyes. It is highly sensitive to the presence
      of bacteria and is rapidly destroyed in a medium in which certain other organisms
      are present. The presence of blood serum (man, sheep, horse, rabbit, etc.) seems
      to be essential for its growth. It grows well at a temperature of about 25-26
      degrees C. and more quickly at 37 degrees C., though at the latter temperature it
      dies out within a few weeks. At 25 degrees C. under favorable conditions and in
      suitable culture media it remains viable for several months without losing its
      virulence. Leptospira icteroides multiplies by transverse division. The virulence
      attained by some strains was such that 0.00001 cc. of a culture could induce
      typical fatal infection in guinea pigs. There exists a considerable variation
      among guinea pigs in their susceptibility to Leptospira icteroides. The organism
      is killed within 10 minutes at a temperature of 55 degrees C. and is also
      destroyed by complete desiccation or freezing and thawing. Bile and bile salts
      dissolve it in certain concentrations, but not saponin. Leptospira icteroides
      passes through the pores of Berkefeld filters V and N, and there is a possibility
      of its having a granular phase of life under certain conditions.

PMID- 19868343
TI  - GROWTH ACCESSORY SUBSTANCES FOR PATHOGENIC BACTERIA IN ANIMAL TISSUES.
AB  - The growth of all the pathogenic bacteria studied was favorably influenced by the
      addition of small amounts of tissue extracts. Beef heart, rabbit and cat tissues,
      and human nasal secretions contain substances favorable to the growth of the
      organisms tested. The mucosa of different organs, spleen, liver, and kidney, are
      relatively rich in these substances, while muscle is relatively poor. The
      favorable effect of the extracts is manifested by an enhancement of growth and a
      reduction of lag. The water-soluble substances are apparently the ones essential
      for bacterial development; the ether extract has no effect on growth. Experiments
      are reported which indicate that the substances in question belong to the class
      of so called vitamines.

PMID- 19868344
TI  - STUDIES ON ORGAN TRANSPLANTATION : I. TRANSPLANTATION OF THE THYROID GLAND WITH
      INTACT BLOOD SUPPLY.
AB  - Our experiments on dogs showed that the thyroid gland which was autoplastically
      transplanted, by means of various methods of blood vessel anastomosis, could live
      in good condition and functionate favorably several months after the operation,
      even after the interruption of the circulation for 1(1/2) hours. They further
      showed that the circulation through the transplanted blood vessels as well as
      glands was as good as normal, and that permanent successful results of the
      homoplastic transplantation of the gland are as yet not possible.

PMID- 19868345
TI  - STUDIES ON ORGAN TRANSPLANTATION : II. TRANSPLANTATION OF THE SPLEEN WITH INTACT
      BLOOD SUPPLY.
AB  - Seven autoplastic transplantations and one homoplastic transplantation of the
      spleen of dogs were made. One autotransplantation was successful, the gland being
      normal at the end of 88 days.

PMID- 19868346
TI  - THE EXPERIMENTAL PRODUCTION IN DOGS OF EMPHYSEMA WITH ASSOCIATED ASTHMATIC
      SYNDROME BY MEANS OF AN INTRATRACHEAL BALL VALVE.
AB  - 1. Experimental emphysema can be produced in dogs by impeding expiration by means
      of a properly constructed ball valve introduced into the trachea. 2. This method
      affords a practical means of study of various physiological, pathological, and
      clinical aspects of emphysema. 3. The experiments demonstrate that any lesion or
      factor capable of interfering sufficiently with proper air expulsion yet
      permitting of sufficient air intake will occasion emphysema. 4. Attacks
      simulating those of asthma are occasioned in experimental emphysematous animals
      after exercise as well as during and following inhalation of mildly irritant
      gases.

PMID- 19868347
TI  - ETIOLOGY OF YELLOW FEVER : V. PROPERTIES OF BLOOD SERUM OF YELLOW FEVER PATIENTS
      IN RELATION TO LEPTOSPIRA ICTEROIDES.
AB  - The serum from a number of persons recovering from yellow fever in Guayaquil was
      studied with a view to establishing its possible immunological relationship with
      a strain of Leptospira icteroides derived from one of the yellow fever patients.
      For this purpose the serum of convalescents was mixed either with an organ
      emulsion of a passage strain, or with a culture of the organism, and inoculated
      intraperitoneally into guinea pigs. The Pfeiffer reaction was first studied, and
      then the animals were allowed to live until the controls, inoculated with the
      same emulsion or culture of Leptospira icteroides but without the serum, or with
      serum from patients suffering from other diseases than yellow fever, had died of
      the experimental infection with typical symptoms A positive Pfeiffer phenomenon
      was observed in fifteen of the eighteen convalescent cases studied, or
      approximately 83 per cent. Sera from ten non-immune soldiers and from two malaria
      patients gave uniformly negative results. Protection from an ultimate fatal
      infection was afforded some of the guinea pigs which received the serum of yellow
      fever convalescents, while the control animals succumbed to the infection with
      typical symptoms. In one instance, in which the serum was tested on the 2nd and
      the 10th days of disease, a Pfeiffer reaction was demonstrated, as well as
      protective property against the infection, in the specimen from the 10th but not
      in that from the 2nd day. From the foregoing observations of immunity reactions
      it appears highly probable that Leptospira icteroides is etiologically related to
      yellow fever.

PMID- 19868348
TI  - INTESTINAL OBSTRUCTION : II. A STUDY OF THE FACTORS INVOLVED IN THE PRODUCTION
      AND ABSORPTION OF TOXIC MATERIAIS FROM THE INTESTINE.
AB  - 1. It is impossible to sterilize the intestine by the use of chemical antiseptics
      even when these are applied directly to the mucosa of isolated segments. 2. The
      mucosa of the alimentary tract does not elaborate an internal secretion which is
      necessary to life, or a secretion which could be disturbed by the conditions of
      acute obstruction so as to account for the symptom complex of that condition. 3.
      The substances responsible for the toxemia in acute obstruction are produced by
      the action of intestinal bacteria on proteins or their split products. 4. An
      injury to the intestinal mucosa, particularly that resulting from disturbances of
      the blood supply to the intestine, greatly facilitates the absorption of these
      poisons. The work of Hartwell and his associates and that of Murphy and Brooks on
      this point are confirmed.

PMID- 19868349
TI  - A STUDY OF PNEUMOCOCCI REACTING WITH ANTIPNEUMOCOCCUS SERA OF TYPES I, II, AND
      III, WITH AN OBSERVATION OF A MUTATION OF ONE OF THE STRAINS.
AB  - In this paper are reported the results of a study of nine strains of pneumococci
      agglutinating with antipneumococcus sera of all three types (Nos. I, II, and
      III). Seven of the strains were the cause of serious or fatal infections in human
      beings. Morphologically they were typical pneumococci with characteristic growth
      on ordinary media. Most of the strains were soluble in bile, fermented inulin,
      and caused no precipitation on glucose ascitic fluid agar. Two of the strains,
      however, resembled streptococci in these three cultural characteristics, but have
      been regarded as pneumococci on account of their serological reactions.
      Variations in the cultural reactions occurred with several strains while they
      were under observation. The virulence of the strains varied greatly, some strains
      being almost non-pathogenic, and others killing mice in doses of 0.000001 cc. of
      a 24 hour broth culture. Antipneumococcus Sera I, II, and III agglutinated all
      the strains in fairly high dilution (1:8 to 1:64 or higher), while normal horse
      serum caused no agglutination. Antipneumococcus Sera I, II, and III stimulated
      active phagocytosis of all the strains, while no phagocytosis occurred in control
      preparations with normal horse serum. These strains elaborated a soluble
      substance in the body of inoculated mice which caused the formation of a
      precipitate when the peritoneal washings, cleared by centrifugalization, were
      added to the antipneumococcus sera of all three types. Antipneumococcus Sera I,
      II, and III protected mice equally well against 1,000 to 10,000 times the minimal
      lethal dose of the two strains with which protection tests could be carried out.
      Absorption of serum of Types I and II with the homologous pneumococcus removed
      the agglutinins and the bacteriotropins for all these strains. Absorption of
      these sera with Strains T and N removed the agglutinins and the bacteriotropins
      for the homologous strain only, and not for typical members of Type I or II, or
      for the other atypically agglutinable strains reported in this paper. The
      agglutinins concerned in the agglutination of these peculiar strains are
      therefore minor agglutinins. As shown not only by agglutination tests, but also
      by protection tests and agglutinin absorption tests, these organisms bear the
      same relation to Types I, II, and III, as do atypical Type II strains to Type II.
      Immune sera were prepared with these strains, and each strain was tested with all
      the immune sera by means of phagocytic and agglutinative reactions. In general,
      the strains were found to be serologically distinct, though some
      interrelationships existed between Strains V and R, and between Strains H, F, and
      N. These sera had no activity towards strains belonging to Type I or II, or
      atypical Type II. A mutation occurred in one of the strains, B, while it was
      under observation. On isolation this strain had the cultural reactions of a
      typical pneumococcus, and had the phagocytic and agglutinative reactions of an
      atypical Type II. After 6 months cultivation on blood agar its serological
      reactions changed, and it became actively phagocyted and agglutinated in
      antipneumococcus sera of Types I, II, and III. Its cultural characteristics also
      changed, and it became bile-insoluble, did not ferment inulin, and caused
      precipitation in glucose ascitic fluid agar. At this time it caused an intense
      green discoloration at the base of the blood agar slants around the water of
      condensation. By repeated animal passages this strain was three times made to
      revert abruptly to its original form (atypical Type IIa), both in cultural and
      serological reactions. An immune serum was prepared to each form of the strain,
      and each serum acted strongly on the homologous form, but was without action on
      the heterologous form of the strain. This mutation suggests that these
      pneumococci reacting with all three types of antipneumococcus sera may represent
      primitive, relatively undifferentiated forms from which the fixed types may have
      arisen.

PMID- 19868350
TI  - STUDIES OF OXYGEN IN THE VENOUS BLOOD : V. DETERMINATIONS ON PATIENTS WITH
      ANEMIA.
AB  - 1. Determinations of the oxygen content and the oxygen unsaturation of the venous
      blood have been performed on patients with varying amounts of hemoglobin. 2. The
      oxygen unsaturation of the venous blood is independent of the oxygen capacity,
      unless the latter is reduced below the normal value for oxygen unsaturation
      (about 5 volumes per cent). In a polycythemic patient, for example, with 33.4
      volumes per cent oxygen capacity (181 per cent hemoglobin), the venous oxygen
      content was. 28 volumes per cent, giving an unsaturation of 5.4 volumes per cent.
      Similarly, in an anemic patient with only 6.7 volumes per cent oxygen capacity
      (36 per cent hemoglobin), the venous oxygen was 1.5, giving an unsaturation of
      5.2 volumes per cent. This means that the tissues extract from the blood all the
      oxygen they need with apparently equal readiness, regardless of whether the
      extraction leaves a great oxygen reserve in the blood as in polycythemia, or
      practically no reserve as in anemia. 3. The results seem to show that the resting
      organism does not increase its circulation until all the reserve oxygen is used.
      This means that the resting anemic organism does not need or use any compensation
      for its anemia until the hemoglobin has sunk below 30 per cent. Below that value
      the organism increases the blood flow in order to secure to the tissues the
      normal amount of oxygen.

PMID- 19868351
TI  - THE STREPTOCOCCI OF EQUINES.
AB  - The lower nasal mucosa and the pharynx of thirty eastern and twenty-three western
      horses have been examined for streptococci. Eight of the eastern horses carried
      non-hemolytic streptococci on the nasal mucosa. From the pharynx of six, non
      hepiolytic streptococci were cultivated. The throats of eighteen contained
      strains of the hemolytic type. The nasal mucosa of the eastern horses failed to
      show hemolytic streptococci. Eight western horses carried non-hemolytic
      streptococci in the nasal passage; eight also harbored the hemolytic type. Twenty
      two strains were isolated from the pharynx. Eleven were hemolytic. Among all the
      non-hemolytic nasal strains those capable of fermenting mannite predominate.
      Those of the non-hemolytic types from the pharynx of both classes of horses may
      or may not ferment lactose but all do ferment either raffinose or inulin. In no
      instance have any of the non-hemolytic types proved pathogenic for mice. The
      hemolytic strains from the nasal mucosa of the western horses were all of the
      Streptococcus py genes type. They were pathogenic for mice and rabbits. One
      strain from the pharynx of an eastern horse and eight from the throats of the
      western horses were of the same species. All the others corresponded closely in
      their fermentation reactions with non-hemolytic streptococci from the same
      region. The streptococci from pathological sources were all hemolytic. They have
      fallen into two groups; the larger group (Streptococcus pyogenes) produced acid
      in dextrose, lactose, saccharose, maltose, milk, and salicin but failed to change
      the reaction of broth containing raffinose, inulin, or mannite. The streptococci
      of the smaller group (Streptococcus equi) differ only in their inability to
      ferment lactose or acidulate milk. Both types are pathogenic for mice. Rabbits
      are usually more resistant. Streptococcus pyogenes has been isolated from
      eighteen of twenty-two cases of influenza, three of six cases of strangles, and
      from eight of nine abscesses. Streptococcus equi was observed in four horses
      suffering from influenza and five others affected with strangles. This species
      was also found in an abscess and associated with both rhinitis and pharyngitis.

PMID- 19868352
TI  - ETIOLOGY OF YELLOW FEVER : VII. DEMONSTRATION OF LEPTOSPIRA ICTEROIDES IN THE
      BLOOD, TISSUES, AND URINE OF YELLOW FEVER PATIENTS AND OF ANIMALS EXPERIMENTALLY
      INFECTED WITH THE ORGANISM.
AB  - Examinations of fresh blood from yellow fever patients by means of the dark-field
      microscope, made in more than twenty-seven cases, revealed in three cases the
      presence of Leptospira icteroides. In no instance was a large number of organisms
      found, a long search being required before one was encountered. The injection of
      the blood into guinea pigs from two of the three positive cases induced in the
      animals a fatal infection, while the blood from the third positive case failed to
      infect the guinea pigs fatally. Careful but by no means exhaustive dark-field
      searches for the leptospira with fresh specimens of blood from the remaining
      cases of yellow fever ended without positive findings, although four of the
      specimens, when injected into guinea pigs, caused a fatal leptospira infection.
      Stained blood film preparations from the corresponding cases were also examined,
      but the percentage showing the leptospira in the blood was no greater than that
      found by examination in the fresh state with the dark-field microscope. In fact,
      owing to the defective stains that were available at the time of the
      investigation a great many slides did not take the proper coloration with
      Giemsa's or Wright's stain and could not be relied upon. Regarding the presence
      of Leptospira icteroides in various organs both dark-field and stained films were
      examined. In only one instance so far a few organisms were detected in the
      emulsion of liver taken shortly after death from a case dying on the 4th day of
      yellow fever. This part of the work will be reported later upon completion.
      Examinations of the urine from different cases of yellow fever were made both by
      dark-field microscope and by inoculation into guinea pigs. The results were
      totally negative in thirteen cases, including many convalescents, but in one case
      one of the guinea pigs inoculated with 10 cc. of the urine came down on the 15th
      day with suggestive symptoms (suspicion of jaundice, and some hemorrhagic and
      parenchymatous lesions of the lungs and kidneys). This specimen showed no
      leptospira by dark-field examination. In experimental infection of guinea pigs
      with Leptospira icteroides the blood became infective in many instances 48 hours
      after inoculation, and was always infective after 72 hours. The liver and kidney
      become infective simultaneously with the blood. Detection of the organism by
      means of the dark-field microscope has seldom been accomplished before the 5th
      day. The organisms are most abundant on the 6th to the 7th day, but become fewer
      or completely disappear before death. In the meanwhile the number of organisms
      increases in the liver and kidney, from which they disappear as the jaundice and
      other symptoms become aggravated. When death occurs these organs seem to have
      lost most of the leptospira) and positive transfer by means of them is less
      certain. At the later stage of the disease the blood is often free from the
      organisms and ceases to be infective. Positive transmission with blood obtained
      from moribund animals is not impossible, however, even when no leptospira can be
      detected under the dark-field microscope.

PMID- 19868353
TI  - ETIOLOGY OF YELLOW FEVER : VIII. PRESENCE OF A LEPTOSPIRA IN WILD ANIMALS IN
      GUAYAQUIL AND ITS RELATION TO LEPTOSPIRA ICTEROHAEMORRHAGIAE AND LEPTOSPIRA
      ICTEROIDES.
AB  - By the inoculation of guinea pigs intraperitoneally with the emulsions of kidneys
      from wild rats and mice captured in Guayaquil, it was found that 67 per cent of
      the wild rats tested harbored in their kidneys a leptospira which produced in
      guinea pigs symptoms and lesions identical with those produced by Leptospira
      icterohamorrhagia derived either from patients suffering from infectious jaundice
      in Japan or Europe, or from wild rats caught in New York. Immune sera were
      prepared in rabbits by injecting different strains of the Guayaquil leptospira.
      These sera had a marked agglutinating and disintegrating influence upon the
      homologous strains, and also, but often to a less pronounced degree, upon the
      strains of Leptospira icterohoemorrhagioe from other sources. Pfeiffer's
      phenomenon was also found to be positive, and protection was demonstrated against
      infection with virulent cultures of strains of Leptospira icterohoemorrhagioe.
      The same sera had no effect, or at most a very slight one, upon Leptospira
      icteroides. Guinea pigs inoculated with icteroides strains were not noticeably
      protected by the use of the immune sera prepared with the Guayaquil rat strains.
      Guinea pigs inoculated with killed cultures of the Guayaquil strains of
      leptospira proved to be resistant to a subsequent infection with heterologous as
      well as homologous strains of Leptospira icterohoemorrhagioe. It is concluded,
      therefore, that the leptospira isolated from the kidneys of wild rats and mice in
      Guayaquil belongs to the group of Leptospira icterohoemorrhagioe, and differs
      from Leptospira icteroides in its immunity reactions. No positive transmission
      was obtained with kidney material from bats and an opossum.

PMID- 19868354
TI  - STUDIES ON THE BIOLOGY OF STREPTOCOCCUS : I. ANTIGENIC RELATIONSHIPS BETWEEN
      STRAINS OF STREPTOCOCCUS HAEMOLYTICUS.
AB  - 1. Immunological differences have been shown to exist between strains of
      Streptococcus hoemolyticus of the human type. 2. Four biological types have been
      identified by means of the reactions of agglutination and protection. 3. At least
      two other types have been encountered and the indications are that more exist.

PMID- 19868355
TI  - THE OXYGEN OF THE ARTERIAL AND VENOUS BLOOD IN PNEUMONIA AND ITS RELATION TO
      CYANOSIS.
AB  - 1. A simple method for arterial puncture is given which does no permanent injury
      to the artery. Arterial and venous punctures have been done on 33 cases of
      pneumonia and five normal subjects, and the blood thus obtained has been studied
      with reference to the oxygen capacity and arterial and venous unsaturation. 2. In
      five normal subjects the mean arterial unsaturation was 5 per cent of the total
      oxygen capacity; the mean venous unsaturation was 26.8 per cent. 3. In the
      pneumonia cases the arterial oxygen unsaturation varied over a wide range. The
      arterial unsaturation varied from 0.0 to 68.2 per cent, the venous from 14.4 to
      85.5 per cent. In the fatal cases as opposed to the non-fatal cases of pneumonia,
      the mean arterial oxygen unsaturation was 32 per cent as against 13.9 per cent.
      As a rule, an arterial unsaturation of over 20 per cent was associated with a
      fatal outcome. Similarly, the mean venous oxygen unsaturation was 57 per cent in
      the fatal cases and 36.3 per cent in the non-fatal cases. 4. In five cases in
      which no cyanosis was observed at any time the mean arterial oxygen unsaturation
      was 5.4 per cent, the mean venous oxygen unsaturation 31.5 per cent. In cases
      which showed cyanosis of varying degree during the course of the illness, the
      mean arterial unsaturation was 24.7 per cent, and the mean venous unsaturation
      44.5 per cent. Cases without cyanosis have an arterial unsaturation close to the
      normal. 5. There is a definite relation between the degree of cyanosis and the
      per cent of arterial unsaturation. With increasing cyanosis the arterial
      unsaturation becomes greater. The venous unsaturation varies similarly. 6. In
      individual cases with marked cyanosis associated with high arterial unsaturation,
      the clinical improvement of the patient and the diminution of the cyanosis are
      accompanied by a similar diminution in the arterial and venous unsaturation.
      Conversely, an increase of cyanosis is accompanied by an increase in arterial
      unsaturation. It is evident that the cyanosis of pneumonia patients is due to the
      incomplete saturation of venous blood with oxygen in the lungs, and that the
      various shades of blue observed in the distal parts are caused by an admixture of
      reduced hemoglobin and oxyhemoglobin in the superficial capillaries. 7. No
      unusually low total oxygen capacities were observed, even in fatal cases with
      intense cyanosis. On the contrary, in these cases the total oxygen capacity was
      unusually high, pointing toward a concentration of the blood. Again in only one
      case was there any marked fall in the oxygen capacity during the illness.
      Therefore, methemoglobin formation, in these cases, can hardly have occurred to
      such an extent as to be an important factor in the production of cyanosis. Of the
      33 cases studied, however, only seven were lobar pneumonia, the rest being of
      types ordinarily unusual, which have accompanied the recent influenza epidemic;
      and of the seven, not all were in all respects typically lobar. The possibility
      still remains, therefore, that in typical lobar pneumonia caused by the
      pneumococcus methemoglobin may play a part in the cyanosis. 8. The oxygen
      consumption, i.e. difference between arterial and venous contents, was within
      normal limits, indicating that the cardiac output was not diminished in the cases
      (chiefly post influenza) of pneumonia studied.

PMID- 19868356
TI  - THE OXYGEN AND CARBON DIOXIDE CONTENT OF ARTERIAL AND OF VENOUS BLOOD IN NORMAL
      INDIVIDUALS AND IN PATIENTS WITH ANEMIA AND HEART DISEASE.
AB  - 1. The oxygen content of venous and of arterial blood from fifteen essentially
      normal individuals at rest in bed has been determined. 2. The percentage
      saturation of the arterial blood has varied between 100 and 94.3. The average is
      95.5 per cent. 3. The oxygen consumption has varied between 2.6 and 8.3 volumes
      per cent. 4. The oxygen content and the percentage saturation of arterial blood
      taken at close intervals from three different peripheral arteries of a normal
      individual have shown values agreeing within the limits of error. Analyses of the
      blood gases of a normal individual, at rest and after exercise, have shown a
      lowering of the percentage oxygen saturation of the arterial blood and a
      diminished carbon dioxide content after exercise. 5. In three persons with severe
      anemia the saturation of the arterial blood has not differed from the normal.
      Very low absolute values were found for the oxygen content of the venous blood,
      but the normal oxygen consumption has been maintained. 6. The carbon dioxide
      content of the arterial blood from ten normal individuals has varied between 54.7
      and 44.6 volumes per cent. That of the venous blood has varied between 60.4 and
      48.3 volumes per cent. 7. No deviations from the normal values for oxygen and
      carbon dioxide were found in venous and arterial blood from cardiac patients
      without arrhytiunias, well compensated, and at rest in bed. 8. A series of
      determinations has been made upon nine cardiac patients with varying degrees of
      decompensation. The percentage oxygen saturation of the arterial blood on
      admission was abnormally low in seven of these cases. With the return to
      compensation and with the clearing up of pulmonary symptoms, the percentage
      saturation of the arterial blood returned to normal in four of them. 9. In a case
      of long standing mitral endocarditis with auricular fibrillation it remained low
      over a period of I month of observation. 10. In a case of chronic myocarditis
      secondary to emphysema and chronic bronchitis, it remained low over the period of
      observation. 11. Normal values for the percentage saturation of the arterial
      blood were found in two individuals with decompensated aortic disease but without
      physical signs of extensive pulmonary involvement. 12. The oxygen consumption
      tended to be high in individuals with cardiac disease during the periods of
      marked decompensation and to be lower as compensation was regained. 13. The data
      presented indicate that at least in many circulatory diseases during
      decompensation, particularly when there are physical signs of pulmonary
      congestion, there is a disturbance of the pulmonary exchange, as indicated by the
      lowering of the percentage saturation of the arterial blood with oxygen.

PMID- 19868357
TI  - STUDIES ON CYANOSIS : I. PRIMARY CAUSES OF CYANOSIS.
AB  - These data prove that abnormally high oxygen unsaturation of the blood is a cause
      of cyanosis. The fact that the lowest value of oxygen unsaturation (in the venous
      blood) associated with cyanosis is about 8 volumes per cent seems to indicate
      that this amount of reduced hemoglobin is the lowest capable of producing a
      cyanotic color. We shall later discuss this point more in detail. Table III shows
      furthermore that in spite of the fact that cyanosis is due to abnormally high
      oxygen unsaturation, no proportionality exists between the intensity of the blue
      color and the amount of reduced hemoglobin. This may in small part be due to
      individual peculiarities of the skin and subcutaneous tissue, which are known to
      influence in anemia the relation between paleness of the skin and the decrease in
      hemoglobin. We shall, however, in the succeeding paper show that the main cause
      of the disproportionality between cyanosis and venous oxygen unsaturation is
      found in another factor, the recognition of which throws a clearer light on the
      pathogenesis of cyanosis, and explains why we may find values of oxygen
      unsaturation as high as 13 volumes per cent in non-cyanotic individuals.

PMID- 19868358
TI  - STUDIES ON CYANOSIS : II. SECONDARY CAUSES OF CYANOSIS.
AB  - 1. The primary cause of cyanosis is an increase in the reduced hemoglobin, or
      oxygen unsaturation, of the blood in the peripheral capillaries. 2. When the mean
      capillary oxygen unsaturation, which is calculated as the mean between venous and
      arterial unsaturation, and is normally about 2 to 3 volumes per cent, is
      increased to about 6 to 7 volumes per cent, cyanosis appears. For this reason 6
      to 7 volumes per cent may be called the threshold value of mean capillary oxygen
      unsaturation for the incidence of cyanosis. 3. The increased mean capillary
      oxygen unsaturation is produced in two ways (secondary causes of cyanosis),
      either by an abnormally great reduction during passage through the capillaries
      (Text-fig. I, Diagram II) or by a state of partial reduction in the arterial
      blood entering the capillaries (Text-fig. I, Diagram III). The first condition
      (abnormally great reduction) occurs during exercise, or when the blood flow is
      retarded, as in decompensated heart condition. The second condition (partial
      arterial unsaturation) occurs in certain lung and heart diseases, and when the
      alveolar oxygen tension is greatly decreased, as at high altitudes. 4. If the
      blood is completely saturated with oxygen in the lungs, the oxygen unsaturation
      of the venous blood may increase to 13 to 14 volumes per cent before cyanosis
      appears. 5. If cyanosis appears at a venous oxygen unsaturation less than 13 to
      14 volumes per cent, some arterial oxygen unsaturation may be assumed, and the
      more the lower the venous oxygen unsaturation is. 6. Even if neither rales nor
      dullness can be detected in the lungs, conditions may exist which prevent
      complete oxidation of the arterial hemoglobin. This is especially frequent in
      patients with mitral lesions. 7. Cyanosis cannot be produced in patients whose
      hemoglobin percentage is below 35 per cent on the Haldane scale (oxygen capacity
      of 6.5 volumes per cent).

PMID- 19868359
TI  - ERYTHROSIS, OR FALSE CYANOSIS.
AB  - 1. In the venous blood of a patient with Vaquez' disease normal values were found
      for the oxygen unsaturation (reduced hemoglobin), although the total hemoglobin
      and oxygen capacity were abnormally high. The carbon dioxide content was normal.
      2. The color of the skin and mucous membranes of this patient was more reddish
      than blue. 3. It is proposed to call the color of the skin in polycythemic
      patients erythrosis in order to distinguish the condition from cyanosis.

PMID- 19868360
TI  - SOME MORPHOLOGICAL AND BIOLOGICAL CHARACTERS OF THE SPIRILLA (VIBRIO FETUS, N.
      SP.) ASSOCIATED WITH DISEASE OF THE FETAL MEMBRANES IN CATTLE.
AB  - Twenty-two fetal and two calf strains of spirilla have been studied chiefly with
      regard to the problem of identity. Twenty-one fetal strains are probably
      specifically the same. One fetal strain differs slightly from these, but in its
      agglutination affinities it belongs to the same group. Of two strains isolated
      from calves one has definite agglutination relations with the fetal strains, the
      other none. In the morphological and biological characters so far investigated
      all the strains agree closely with one another.

PMID- 19868361
TI  - THE ETIOLOGICAL RELATION OF SPIRILLA (VIBRIO FETUS) TO BOVINE ABORTION.
AB  - The isolation in pure culture of a definite morphological entity (vibrio or
      spirillum) with practically the same biological characters from a series of cases
      of the same clinical complex (abortion) establishes a presumption in favor of the
      specific identity of the organisms and also in favor of the inference that such
      organisms are etiologically related to the diseased condition. This presumption
      is strengthened by the fact that disease of the fetal membranes followed the
      injection of pure cultures of this organism in two out of four cases.

PMID- 19868362
TI  - THE BACTERIOLOGY OF BOVINE ABORTION, WITH SPECIAL REFERENCE TO ACQUIRED IMMUNITY.
AB  - In a large herd of dairy cattle and young stock the bacteriological examination
      of 109 cases of abortion which included a relatively thorough study of the fetus
      and a study of the membranes, or swabs from the uterus whenever obtainable, gave
      the following results. 62, or 57 per cent, were associated with Bacillus abortus.
      26, or 23.8 per cent, were associated with spirilla. 2, or 1.8 per cent, were
      associated with Bacillus pyogenes. 19, or 17.4 per cent, were either sterile or
      else the digestive and respiratory tracts had been invaded during or after birth
      with miscellaneous bacteria. Bacillus abortus was absent according to cultures
      and animal tests. Such a relatively large proportion of cases of abortion without
      Bacillus abortus as the inciting agent is noteworthy. In general Bacillus abortus
      was associated with first pregnancies. Its presence diminished rapidly in
      frequency in later pregnancies. Assuming in a general way that purchased cows
      coming from small herds were free from any immunity and that their first
      pregnancy in the new herd is equivalent to that of a native heifer and may be
      counted as the first, we have Bacillus abortus associated with the first
      pregnancy in 42, with the second in 14, with the third in 5, and with the fourth
      in 1. Spirilla were distributed as follows: (a) in purchased cows, first
      pregnancy, 6; second pregnancy, 9; third pregnancy, 5; and fourth pregnancy, 3;
      (b) in native cows, first pregnancy, 0; third pregnancy, 1; sixth pregnancy, 1;
      and eighth pregnancy) 1. The relation of infection with spirilla to acquired
      immunity is not clear and more data from large herds are needed to define both
      etiological and immunological bearings of the spirilla. Thus far spirilla have
      not been encountered in native heifers of the herd giving birth the first time. A
      tentative explanation to be offered is that the young stock is kept segregated
      from the older and purchased cows until shortly before calving. The occasional
      discharge of a fetus among the young stock in pasture tends to keep up the
      disease due to Bacillus abortus. Later on association with older cows brings
      about infection with spirilla (Vibrio fetus) and more rarely with other possible
      agencies of fetal disease. On the other hand, abortions may occur among the
      pastured stock from time to time and remain unrecognized. Not until both groups
      of animals are subjected to the same daily scrutiny will it be possible to affirm
      that abortion associated with spirilla does or does not occur among young stock.

PMID- 19868363
TI  - AN INTERPRETATION OF THE AGGLUTINATION REACTION TO BACILLUS ABORTUS IN 75 CASES
      OF BOVINE ABORTION BACTERIOLOGICALLY CONTROLLED.
AB  - The agglutination test when carried out so as to give the entire range of serum
      dilutions to the limit of clumping is a delicate test which reflects a variety of
      conditions involved in infection with Bacillus abortus. Among these conditions
      are its time relation to the act of abortion and the length of time the abortion
      bacilli live and multiply in the pregnant uterus. It is obvious that if a uterus
      be infected in the 8th month of pregnancy, the opportunity for agglutinins to
      accumulate are poorer than if the uterine infection lasts 3 or 4 months. The
      presence of Bacillus abortus in the udder determines in many cases the intensity
      of the reaction. No definite rules can therefore be formulated for the
      interpretation of the agglutination reaction quantitatively, since it is bound up
      with a complicated process varying from case to case. In the individual cow in
      general a titer of 1:40 or less may be regarded as indicating that the cow is not
      infected with Bacillus abortus at the time of the blood examination. It does not
      exclude former infections in the case of older cows, nor does it absolutely
      exclude very recent infection (Nos. 278 and 351). The highest titers, 1:640 and
      above, generally indicate recent infection and in the absence of recent premature
      births infection of the udder. Even when abortion has just occurred, it may be
      due to other agencies and the high titer maintained by a chronic infection of the
      udder dating from an earlier uterine infection with Bacillus abortus.
      Intermediate titers may indicate a gradual rise or decline of agglutinins
      preceding or following abortion without infection of the udder. They may also
      stand for a relatively high resistance or partial immunity of the cow. In any
      herd a uniformly low titer (1:40 or less) in all animals may be regarded as
      indicating the entire absence of Bacillus abortus. A high titer in any one cow
      serves to indicate quite definitely the presence of infection in the herd. To
      determine more accurately the character of the infection in any individual cow
      there is needed in addition to the quantitative agglutination test a
      bacteriological study of the milk and of any prematurely discharged calf or
      fetus.

PMID- 19868364
TI  - HYDROGEN ION CONCENTRATION OF CULTURES OF PNEUMOCOCCI OF THE DIFFERENT TYPES IN
      CARBOHYDRATE MEDIA.
AB  - 1. The optimum hydrogen ion concentration for growth of pneumococcus is pH 7.8.
      2. In broth cultures growth of pneumococcus continues until a final hydrogen ion
      concentration of about pH 5.0 is reached, if sufficient fermentable carbohydrate'
      (above 0.4 per cent) is present. Apparently this acidity is sufficient in itself
      to stop growth. 3. If less carbohydrate is present in the medium growth ceases at
      a lower hydrogen ion concentration, apparently because of exhaustion of
      carbohydrate. If no carbohydrate is present save that extracted from the meat of
      which the broth is made (plain broth medium), growth initiated at pH 7.8 (optimum
      reaction) ceases at about pH 7.0. 4. If bacteria-free filtrates of plain broth
      cultures in which growth has ceased are readjusted to pH 7.8 and reinoculated
      with pneumococcus, no growth occurs unless carbohydrate is added. However, if
      bacteria-free filtrates of dextrose broth cultures in which growth has ceased (pH
      5) are readjusted to pH 7.8 and reinoculated with pneumococcus growth occurs. 5.
      Cultures of pneumococcus with all the carbohydrates which were fermentable under
      the conditions used, namely maltose, saccharose, lactose, galactose, raffinose,
      dextrose, and inulin, gave identical results in the rate of reaction change, and
      final hydrogen ion concentration (pH 5.0) attained. 6. The different
      immunological types of pneumococcus, for the limited number of strains studied,
      behaved alike in fermenting the carbohydrates mentioned above.

PMID- 19868365
TI  - THE RELATION OF PROTEOLYTIC ENZYMES IN THE PNEUMONIC LUNG TO HYDROGEN ION
      CONCENTRATION. AN EXPLANATION OF RESOLUTION.
AB  - Evidence is given of the presence in the cellular material obtained from the
      pneumonic lung of a proteolytic enzyme digesting coagulated blood serum at
      hydrogen ion concentrations of 7.3 to 6.7 and inactive at higher; i.e., more acid
      concentrations. In addition, evidence is brought forward of the presence in the
      cellular material from the pneumonic lung of a proteolytic enzyme splitting
      peptone to amino-acid nitrogen. This enzyme is operative at hydrogen ion
      concentrations from 8.0 to 4.8, but most active at 6.3 or 5.2. These findings may
      be regarded as having a bearing on resolution in pneumonia. During the course of
      the disease a gradual increase in the hydrogen ion concentration of the exudate
      probably takes place. With the breaking down of cellular material an enzyme
      digesting protein (fibrin) in weakly alkaline and weakly acid media may be
      liberated. With a gradual increase in the hydrogen ion concentration of the
      pneumonic lung the action of this enzyme probably ceases. An enzyme capable of
      splitting peptone to amino-acid nitrogen is probably active during the
      proteolysis of the fibrin and further activated when the hydrogen ion
      concentration of the pneumonic lung is increased to within its range of optimum
      activity at a pH of 6.3 and 5.2. By this means it may be conceived that the
      exudate is dissolved and resolution takes place.

PMID- 19868366
TI  - THE RELATION OF THE PNEUMOCOCCUS TO HYDROGEN ION CONCENTRATION, ACID DEATH-POINT,
      AND DISSOLUTION OF THE ORGANISM.
AB  - 1. In the growth and death of the pneumococcus in fluid media containing 1 per
      cent glucose the production of acid is the most important bactericidal factor. 2.
      1 per cent glucose bouillon cultures of the pneumococcus allowed to grow and die
      out usually reach a final acidity of a pH of about 5.1. 3. At a hydrogen ion
      concentration of about 5.1 or higher, the pneumococcus does not survive longer
      than a few hours. 4. In hydrogen ion concentrations of about 6.8 to 7.4 the
      pneumococcus may live for at least many days. 5. In the intervening hydrogen ion
      concentrations, between 6.8 and 5.1, the pneumococcus is usually killed with a
      rapidity which bears a direct relation to the hydrogen ion concentration; i.e.,
      the greater the acidity the more rapid is the death. 6. Cloudy suspensions of
      washed pneumococci in hydrogen ion concentrations varying from 8.0 to 4.0 show,
      after incubation, dissolution of organisms in lower hydrogen ion concentrations
      than about 5.0. This dissolution is most marked at about 5.0 to 6.0. Some
      dissolution also takes place toward the more alkaline end of the scale. No
      dissolution occurs at the most acid end of the scale.

PMID- 19868367
TI  - ETIOLOGY OF YELLOW FEVER : IX. MOSQUITOES IN RELATION TO YELLOW FEVER.
AB  - The foregoing experiments show that symptoms and lesions closely resembling those
      of yellow fever in man may be induced in guinea pigs by the bite of female
      stegomyias that have previously sucked the blood of a yellow fever patient or of
      an animal experimentally infected with Leptospira icteroides. With mosquitoes
      infected directly from a yellow fever patient the infectivity seems to become
      manifest after a longer period of incubation than with those infected with the
      animal blood. In the former, at least 12 days are said to be necessary before
      they become infectious, and this hypothesis seems to be borne out by the present
      experiment. On the other hand, the mosquitoes which were engorged with the
      infected blood of the guinea pig were found to be capable of transmitting the
      disease within 8 days after the feeding. This discrepancy may be explained by the
      fact that the number of leptospira existing in experimentally infected guinea
      pigs is far greater than that in human blood. The frequency with which positive
      transmission by the stegomyia was obtained in both instances was very small
      indeed, in view of the number of mosquitoes employed. It appears that even under
      natural circumstances the percentage of mosquitoes that eventually become
      infected with the yellow fever microbe by sucking the blood may be very small. It
      has already been shown by previous investigators that to transmit yellow fever
      from a patient to a non-immune person requires from 0.1 to 2 cc. of blood at the
      height of disease. According to my estimate a female stegomyia may take up 0.01
      cc. or even less. Apparently a mosquito occasionally becomes infectious by taking
      up the one or two organisms which happen to be circulating in the peripheral
      blood of man, and it is these occasionally infected few which carry the disease.
      It is not difficult to realize the extent of ever increasing danger from a
      constant supply of the microbic virus which an endemic center or an epidemic of
      yellow fever can provide. One infected mosquito may mean many patients, and the
      life of such a mosquito is usually longer than that of the persons whom it
      fatally infects. Finally, it is of interest to note that the development and
      maintenance of Leptospira icteroides are indispensably associated with the blood
      constituent, the serum, and this is amply supplied by the bloodsucking insect.
      The organism is one of the most fragile of all the pathogenic parasites and
      cannot survive the concurrence of other less fastidious organisms such as
      bacteria. The comparatively aseptic body cavity of the stegomyia furnishes a
      secure shelter for the parasite, which undoubtedly penetrates the zone of safety
      as soon as it is taken into the stomach of the insect. Unlike many other
      parasites this organism is capable of penetrating the intact skin or a
      bacteriaproof filter, and hence it is probably an easy matter for it to pierce
      the tissue of the visceral organs of the mosquito. Whether or not Leptospira
      icteroides can survive and multiply only in the body of Stegomyia calopus and not
      in other varieties or genera is yet to be determined. Another interesting fact
      with regard to the extrinsic life of this organism is that it can multiply
      steadily at a temperature from 18-37 degrees C. The optimum temperature, at which
      it remains viable for many months, is 26 degrees . The climate in most of the
      tropical countries offers optimum conditions both for Leptospira icteroides and
      for the mosquito which carries and nourishes it.

PMID- 19868368
TI  - CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS : CHEMICAL SERIES. I. N
      PHENYLGLYCINEAMIDE-p-ARSONIC ACID.

PMID- 19868369
TI  - CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS : BIOLOGICAL SERIES. I. THE
      TOXIC ACTION OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID.
AB  - The essential facts to be gathered from these studies of the toxicologic action
      of N-phenylglycineamide-p-arsonic acid may be summarized very briefly. The
      substance is one which lends itself well to almost any method of administration
      and can be given to animals in very large doses. The tolerance of different
      animal species varies rather widely but with one exception the reaction of
      laboratory animals to toxic doses of the drug is of favorable character. That is,
      toxic effects are confined to doses relatively close to the minimum lethal dose
      and the recovery of animals from sublethal intoxications is remarkably rapid and
      complete. This feature of the action of the drug makes possible the repeated
      administration of even very large doses at comparatively short intervals of time
      without incurring the dangers incident to cumulative action or to superposition
      of toxic effects. On the contrary, by taking advantage of this peculiarity of
      action, it is possible to develop such a degree of tolerance on the part of
      animals that the dose of the drug administered can be progressively increased to
      a point well above that which is fatal to the normal animal, and this stands out
      as the feature of the toxicologic action of N-phenylglycineamide-p-arsonic acid
      which is of greatest significance in the use of the drug for therapeutic
      purposes.

PMID- 19868370
TI  - CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS : BIOLOGICAL SERIES. II.
      THE THERAPEUTIC ACTION OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID IN EXPERIMENTAL
      TRYPANOSOMIASIS OF MICE, RATS, AND GUINEA PIGS.
AB  - N-PhenyIglycineamide-p-arsonic acid is an agent of marked therapeutic action in
      the treatment of experimental trypanosomiasis of mice, rats, and guinea pigs. It
      possesses an average curative range of from 0.2 to 0.3 gm. per kilo of body
      weight of the sodium salt against a 24 hour infection in mice and rats produced
      by several species of pathogenic trypanosomes. Since the lethal dose for mice is
      from 2 to 2.25 gm. and for rats 0.75 gm. per kilo of body weight, we have
      curative ratios of 1:8 and 1:3 respectively. The curative dose for guinea pigs is
      0.15 gm. per kilo of body weight, thus giving a curative ratio of 1:10. The
      trypanocidal activity of this compound is relatively rapid in all three animal
      species, for the peripheral blood is cleared of organisms within 24 hours after
      its administration, and in addition, the lower limits of the curative range are
      comparatively sharply defined. Intraperitoneal, intravenous, and subcutaneous
      routes of administration for all practical purposes may be considered equally
      efficacious in Tr. brucei infections of mice both as regards the speed of action
      of the drug and the average curative range. The administration of the drug in
      therapeutic amounts in all three animal species is not followed by manifestations
      of organic or functional injury, but, on the contrary, the genera] physical
      condition of the treated animals shows an immediate and continued marked
      improvement. The therapeutic activity in trypanosomiasis of mice, rats, and
      guinea pigs as evidenced by the relative speed and sharpness of action, together
      with the curative ratio as expressed in fractions of the minimum lethal dose, and
      the absence of organic injury or functional disturbance following therapeutic
      doses are significant and characteristic features of the amide of N-phenylglycine
      p-arsonic acid.

PMID- 19868371
TI  - CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS : BIOLOGICAL SERIES. III.
      THE THERAPEUTIC ACTION OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID IN EXPERIMENTAL
      TRYPANOSOMIASIS OF RABBITS.
AB  - In the treatment of experimental trypanosomiasis of rabbits with subsequent
      appraisal of the value of the therapeutic agent used, there are certain
      experimental factors including uniform infecting strains of trypanosomes and the
      observation of general procedures of method and time of inoculation conditioned
      by the infection itself which must be taken into account. The conspicuous and
      characteristic clinical signs and symptoms seen in rabbit trypanosomiasis serve
      as criteria of the severity and duration of the disease, and it is obvious that
      the infection should be well established before treatment is instituted. For the
      same reason, before the question of a permanent cure can be established, treated
      rabbits should be kept under observation for a sufficient period of time, which
      with the species of organisms that we have used is at least 3 months. The
      therapeutic results with the amide of N-phenylglycine-p-arsonic acid were
      obtained in rabbits which showed well marked clinical signs of a definitely
      established disease, and in many instances the infection was extremely advanced
      and of prolonged duration. The five species which we have employed, Tr. brucei,
      Tr.gambiense, Tr. equinum, Tr. equiperdum, and Tr. evansi, are uniformly fatal in
      rabbits. With the usual acute, actively progressing infection of from I to 2
      weeks duration produced by our strain of Tr. brucei, the drug has a curative
      range of from 0.2 to 0.35 gm. per kilo of body weight, when administered
      intravenously in single doses, or from one-third to one-half the minimal lethal
      dose. Of the twenty-nine rabbits treated with doses falling within this range,
      twenty-five, or 86 per cent, were permanently cured and there were no relapses
      observed with doses above 0.3 gm. The infection produced by our strain of Tr.
      gambiense is controlled by a slightly lower dose, since there were no relapses
      with single doses of 0.3 gm. and a single dose of 0.15 gm. effected a cure in one
      of three rabbits so treated. The therapeutic experiments with Tr. equinum, Tr.
      equiperdum, and Tr. evansi are too few to admit of final conclusions, but
      apparently from the evidence at hand, much the same curative range is operative
      in Tr. evansi infections, while larger doses or a different system of treatment
      should have been employed in the treatment of rabbits infected with our strains
      of Tr. equinum and Tr. equiperdum. In addition to the ultimate curative results
      obtained with single doses within the curative range, it is important to consider
      the marked therapeutic action with smaller single doses, as shown by the rapid
      regression and healing of the clinical lesions of the acute infections produced
      by all five species of trypanosomes together with a marked improvement in the
      general physical state of the animal. Moreover, large single doses, above those
      of the so called curative range, caused no disturbance of a toxic nature and were
      apparently well borne. A system of repeated dose therapy may be employed with
      advantage in the treatment of both initial and relapsed infections in rabbits,
      especially in those instances in which there is induration or even necrosis of
      tissues with weakness and emaciation of the animal host. The factor of time of
      repetition or the spacing of doses is in our experience as important as that of
      size of the dose employed and depends upon the rate, degree, and duration of
      action of the particular dose of the drug in question. Since the amide of N
      phenylglycine-p-arsonic add apparently possesses the power of tissue penetration
      to a marked degree, it is desirable to give the second dose within a short time
      after the first in order that it may have a full opportunity for the immediate
      and complete development of its action. The repetition of small doses such as
      0.15 gm. per kilo of body weight on successive or alternate days has given
      successful results as regards both the immediate regression and healing of
      lesions and ultimate permanent cures in severe, chronic infections. It is
      possible, however, to administer increasingly large doses, if this is necessary,
      since infected as well as normal rabbits exhibit a remarkable tolerance to
      repeated large doses of the drug. The therapeutic activity of small doses
      administered intramuscularly is quite comparable with that observed after similar
      doses given intravenously, as indicated by the rate of regression and healing of
      clinical lesions, while such effects proceed somewhat more slowly after
      subcutaneous injections. Permanent cures have been obtained in Tr. brucei
      infection with intramuscular and subcutaneous administration of single doses of
      from 0.2 to 0.5 gm. of the drug per kilo of body weight and in other instances
      with three repeated doses of 0.1 gm. per kilo given intramuscularly. One severely
      infected rabbit which received 0.75 gm. per kilo per os immediately following a
      small dose of sodium bicarbonate was also cured. The therapeutic experiments here
      reported represent only a portion of those carried out with N-phenylglycineamide
      p-arsonic acid and the scope of the present paper does not permit a detailed
      description of the many phases of the experiments or a full discussion of the
      various factors involved and the results obtained, all of which we hope to
      publish at some future time.

PMID- 19868372
TI  - CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS : BIOLOGICAL SERIES. IV.
      THE ACTION OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID UPON SPIROCHETE INFECTIONS.
AB  - To summarize the results obtained from these experiments, one may say that N
      phenylglycineamide-p-arsonic acid is capable of exercising a very definite effect
      upon the course of infections produced by spirochetes of the recurrens group and
      by Treponema pallidum. It is more difficult to say, however, just how these
      effects should be interpreted. In the case of the blood spirochetes, the
      infection is ameliorated, and even though the spirochetes are not immediately
      destroyed, the infection is frequently brought to a termination which leaves the
      animal in a condition not unlike that produced by more powerful spirocheticidal
      agents. That is, the infecting organisms are either affected in such a way that
      they eventually die off or are destroyed by the host in such a way that no
      lasting immunity is developed in consequence of their destruction. Apparently
      much the same type of reaction occurs in the treatment of rabbits infected with
      Treponema pallidum. It is possible that when very large doses of the drug are
      used, these organisms may be completely destroyed, but it is certain that in
      other cases, where complete healing of the lesions is accomplished as a result of
      treatment, the organisms are not destroyed. Moreover, it appears that such a
      result can be accomplished in the presence of numerous actively motile
      spirochetes, and once the effect of the drug has reached this point, either the
      capacity of the spirochetes for stimulating reaction on the part of the tissues
      is lowered or else the reactivity of the tissues is reduced. At any rate., living
      spirochetes may remain in the tissues for considerable periods of time without
      giving rise to the usual tissue reaction which characterizes these infections.
      With either group of organisms, therefore, N-phenylglycineamide-p-arsonic acid
      appears to act in a manner somewhat different from that of the usual
      spirocheticidal agents. While it does possess a considerable degree of
      spirocheticidal action, its chief effect is seen in the peculiar manner in which
      it modifies or controls the course of these infections. Further than this, we
      shall not attempt to go at present. As set forth in the literature, the facts and
      principles upon which such experiments depend are so few as to offer almost no
      basis for an interpretation of these experiments. When we have had an opportunity
      of reporting our own experience in dealing with these infections, we may return
      to a consideration of the facts here reported.

PMID- 19868373
TI  - THE OCCURRENCE OF BACILLUS INFLUENZAE IN THE NORMAL THROAT.
AB  - 1. The frequency of occurrence of Baculus influenzoe in the throats of normal
      individuals has been as great in the period subsequent to the epidemic of
      influenza as it was during the period of the epidemic. 2. Bacillus influenzoe may
      persist in the throats of healthy carriers for a considerable period of time. 3.
      A considerable proportion of individuals not exposed during the epidemic has been
      found to carry Bacillus influenzoe in their throats. 4. Oleate hemoglobin agar
      has been found to be a very satisfactory selective medium for cultivation of
      Bacillus influenzoe from the throat. To give optimum results it should have a
      reaction of from pH 7.2 to 7.5.

PMID- 19868374
TI  - THE PATHOLOGICAL CHANGES IN THE TESTES IN EPIDEMIC PNEUMONIA.
AB  - The testicular changes in pneumonia are without clinical manifestations, are non
      specific, focal in character, independent of the infecting organisms or the
      antecedent disease, and vary in severity directly with the total length of the
      illness. The process is a continuous one, divisible into stages in which the
      following features are recognizable: (1) cessation of spermatogenesis; (2)
      degeneration of preformed spermatocytes, spermatids, and spermatozoa; (3)
      desquamation of altered cells and fragments of the same; (4) formation of giant
      cells in the tubule walls with subsequent liberation into the lumen; (5)
      disappearance of all desquamated cells and all those derived from the
      spermatogonia by mitosis; (6) in some instances thickening of the hyaline layer
      of the basement membrane. Older lesions are frequently found which continue the
      structural alteration of the tubules by hyalinosis and destruction of cells until
      they ultimately disappear. These lesions are not believed to be connected with
      the present illness. Edema may represent the acute injury in another form, and
      round cell infiltration suggests that possibly other factors than toxins may have
      a part in the tissue alterations. In the absence of definite evidence to the
      contrary, the cause is assumed to be circulating toxins, as Wolbach (12) claims
      for influenzal cases. The hemolytic streptococcus produced more extensive
      changes, both epithelial and interstitial, in primary pneumonia occurring during
      the measles epidemic than when pneumonia followed as a secondary infection; in
      the latter cases the pulmonary complications covered a relatively shorter period.
      Measles and epidemic influenza had little apparent effect upon the testes, except
      that the former caused mild inhibition of spermatogenesis; evidence regarding the
      latter is inconclusive. The Pfeiffer bacillus was always associated with other
      organisms, in primary infections and in those following measles. It occurred
      alone in a few cases after epidemic influenza, but the testicular lesion was not
      distinctive. The pneumococcus when alone in primary infections or after an
      epidemic disease produced a uniformly mild picture which was not intensified when
      associated with the influenza bacillus. Giant cells were much more frequent after
      influenzal pneumonia regardless of its cause and were associated with large
      numbers of other desquamated cells. They are formed in the walls of tubules by
      futile mitotic effort and incomplete protoplasmic separation, the abnormality of
      the process being further suggested by the early severing of cytoplasmic
      attachments and rapid desquamation. The series is unique in its uniformity, in
      the care exercised in the bacteriological examinations, and in the relative
      freedom from complicating factors.

PMID- 19868375
TI  - A STRAIN OF CONNECTIVE TISSUE SEVEN YEARS OLD.
AB  - 1. A strain of connective tissue is still very active after more than 7 years of
      life in vitro. 2. The rate of growth of the fragments of tissue can be measured
      accurately and used for testing the action of many different factors on the
      growth of connective tissue cells. 3. The rate of growth of the strain is at
      least as rapid as it was 5 years ago, and may be more active. 4. The connective
      tissue cells appear to have the power of multiplying indefinitely in a culture
      medium, as do microorganisms.

PMID- 19868376
TI  - STREPTOLYSIN PRODUCTION IN CARBOHYDRATE MEDIA.
AB  - It is evident that there are numerous interacting factors which affect
      streptolysin in the presence of fermented sugars. The principal action is the
      change in the metabolism of the streptococcus by which more carbohydrate and less
      protein is utilized; although the growth is much increased there is
      proportionately less hemolysin. The acid developed in these cultures not only
      lessens the vitality of the growing organism and so lessens proteolysis, but is
      destructive to hemolysin at incubator temperature. The concentration of the acid
      produced causes some hemolysis, and a coincident brown discoloration of the
      hemoglobin. These principles may be applied to both liquid and solid media.

PMID- 19868377
TI  - PFEIFFER'S BACILLUS AND INFLUENZA : A SEROLOGICAL STUDY.
AB  - It has been shown that the sera of patients convalescent from influenza yield
      reactions for agglutinins, precipitins, and complement-binding bodies with
      antigens of Pfeiffer's bacillus. These reactions appear constantly at the end of
      the 1st week, increase in intensity during the 2nd week, and remain demonstrable
      for a period of 2 to 4 months. They were most complete in the sera of patients
      suffering from postinfluenzal pneumonia. It has also been demonstrated that the
      strains of Pfeiffer's bacillus isolated during the epidemic were morphologically
      and biologically similar to the strains isolated from influenza cases in other
      years, and antigenically they differed from them only quantitatively. The
      patients' serological reactions indicate the parasitic nature of the bacillus,
      but are not sufficiently stable and clean-cut to signify that Pfeiffer's bacillus
      is the specific inciting agent of epidemic influenza. They do, however, indicate
      that the bacillus of Pfeiffer is at least a very common secondary invader in
      influenza, and that its presence influences the course of the pathological
      process.

PMID- 19868378
TI  - A STUDY BY THE SINGLE CELL METHOD OF THE INFLUENCE OF HOMOLOGOUS ANTIPNEUMOCOCCIC
      SERUM ON THE GROWTH RATE OF PNEUMOCOCCUS.
AB  - 1. Under the conditions stated pneumococci grow as readily in the serum of horses
      highly immunized to the homologous organism as they do in normal horse serum, and
      the rate of growth is not appreciably diminished. 2. This failure of immune serum
      to affect the growth rate is not altered when fresh rabbit blood, fresh human
      blood, or rabbit blister fluid is added in order to supply any hypothetical
      complement which might be lacking. 3. We have not been able to show that when
      immune horse serum is injected intravenously into rabbits or intraperitoneally
      into mice, it acquires the property of killing pneumococci or inhibiting their
      growth. 4. Experimental evidence has been obtained indicating that in the
      peritoneal cavity of the passively immunized mouse the growth of extracellular
      pneumococci continues at apparently the normal rate, until the bacteria are
      engulfed by phagocytes. 5. The immunizing and protective power of
      antipneumococcic serum probably depends, in part at least, on properties which
      are not at present known. It has not been possible in the present study to
      demonstrate that one of these properties consists in delaying the growth of
      pneumococci.

PMID- 19868379
TI  - ANTIBLASTIC PHENOMENA IN ACTIVE ACQUIRED IMMUNITY AND IN NATURAL IMMUNITY TO
      PNEUMOCOCCUS.
AB  - The paper gives the results of a series of experiments made with a special
      technique for the purpose of testing whether or not so called antiblastic
      phenomena or bactericidal phenomena play any part in immunity to pneumococcus.
      The technique employed is that devised by the writer and consists in the
      isolation of single bacteria and their growth in hanging drops where growth can
      be continuously observed. From these experiments it may be concluded that: (1)
      Whole fresh blood, coagulated plasma, or serum of the immunized horse added
      directly to pneumococci, has considerable inhibiting action on the growth of
      pneumococci. The inhibiting effect of the fresh blood, coagulated plasma, or
      serum of a normal horse, however, is as marked as that of a horse highly
      immunized to pneumococci of the same type. This property, therefore, does not
      seem to be of importance in acquired immunity in the horse. No such property has
      been demonstrated in whole fresh rabbit blood. (2) It has been impossible to
      demonstrate that antiblastic phenomena play any part in natural immunity to
      pneumococcus, at least as far as the immunity of the pigeon is concerned. The
      whole fresh blood of the pigeon under the conditions employed exhibits no
      inhibiting action on the growth rate of pneumococci.

PMID- 19868380
TI  - BLOOD VISCOSITY : I. CONDITIONS AFFECTING THE VISCOSITY OF BLOOD AFTER WITHDRAWAL
      FROM THE BODY.
AB  - Small amounts of potassium oxalate probably have no effect on the viscosity of
      the blood and changes hitherto ascribed to it can be attributed either to
      variation in carbon dioxide content or to sedimentation of the red blood cells.
      The viscosity of blood when exposed to the air increases rapidly. This change
      accompanies a loss of carbon dioxide and can be prevented by stoppering the
      container and agitating until the blood comes into carbon dioxide equilibrium
      with the air above it, when the viscosity remains constant. It is essential in
      determining the viscosity of blood that the red cells should be uniformly
      suspended throughout the plasma. This can be accomplished by rotating 5 to 10 cc.
      of blood in a separating funnel for 1 minute.

PMID- 19868381
TI  - BLOOD VISCOSITY : II. EFFECT OF INCREASED VENOUS PRESSURE.
AB  - A rise in venous pressure caused by application of a loose binder to the arm
      results in a marked increase in the viscosity of the whole blood which is
      primarily due to a concentration of the blood in the capillaries. This
      concentration is shown by an increase in the viscosity and total nitrogen of the
      plasma, an increase in the relative volume of the red blood cells, and an
      increase in the relative percentage of hemoglobin. Change in the viscosity of
      whole blood following venous stasis apparently bears no demonstrable relation to
      the carbon dioxide or oxygen content.

PMID- 19868382
TI  - THE EFFECT OF HYPOTONIC AND HYPERTONIC SOLUTIONS ON FIBROBLASTS OF THE EMBRYONIC
      CHICK HEART IN VITRO.

PMID- 19868383
TI  - THE LYMPHOCYTE IN NATURAL AND INDUCED RESISTANCE TO TRANSPLANTED CANCER : V.
      HISTOLOGICAL STUDY OF THE LYMPHOID TISSUE OF MICE WITH INDUCED IMMUNITY TO
      TRANSPLANTED CANCER.
AB  - Mice immunized against cancer by means of an injection of defibrinated blood show
      in the germinal centers of the lymphoid organs a marked increase in the numbers
      of mitotic figures. The increase becomes evident 48 hours after the injection in
      the majority of instances and reaches its climax at about the 5th day. After this
      time it subsides, returning to the normal rate about the 10th day. These
      immunized animals, when inoculated with a cancer graft 10 days after the
      injection, show a second stimulation of the lymphoid centers similar to the first
      but more intense in character. This increase in the number of mitotic figures
      becomes evident as early as 24 hours after the cancer inoculation and persists in
      a marked degree for a week, after which there is a gradual return to the normal
      rate. The lymphocytes of the circulating blood during the establishment of the
      immunity show frequent examples of amitotic division, and many examples of
      irregular and lobulated nuclei. These changes suggest intensified functional
      activity. Contrary to the statement of Da Fano, cellular reaction in the
      subcutaneous tissues of immunized animals is present only in the region
      infiltrated by the injected cells. This fact becomes conspicuous when the
      immunizing injection is given intraperitoneally, in which case no cellular
      accumulations are noted in the loose connective tissues. No constant cellular
      changes were noted in the bone marrow, thymus or thyroid gland, liver, or kidney
      of the treated animals.

PMID- 19868384
TI  - A METHOD OF STANDARDIZING BACTERIAL SUSPENSIONS.
AB  - The opacity of a bacterial suspension is measured by the length of the column of
      the suspension required to cause the disappearance of a wire loop. By a simple
      formula the measured opacity is translated into terms of the concentration of
      bacteria per cc., and so made comparable with that of other suspensions of the
      same organism. An instrument for measuring the opacity of bacterial suspensions
      is described in detail.

PMID- 19868385
TI  - STUDIES ON X-RAY EFFECTS : V. EFFECT OF SMALL DOSES OF X-RAYS OF LOW PENETRATION
      ON THE LYMPHOID TISSUE OF MICE.
AB  - A dose of x-rays governed by the following factors induces a stimulation of
      lymphoid tissue in mice: spark-gap (7/8) inch, milliamperage 25, distance 8
      inches, time of exposure 10 minutes. Within 4 days after this dose there appeared
      an abnormally large number of mitotic figures in the lymphoid tissue of spleen
      and lymph glands, indicating an acceleration of the proliferative activity of the
      tissue.

PMID- 19868386
TI  - TOXINS AND ANTITOXINS OF BACILLUS DYSENTERIAE SHIGA.
AB  - With the methods which have been described we have separated an exotoxin and an
      endotoxin from cultures of the Shiga dysenteric bacillus. The study of the nature
      and effect of the poison of this microorganism is thus simplified. The two toxins
      are physically and biologically distinct. The exotoxin is relatively heat-labile,
      arises in the early period of growth, and yields an antiexotoxic immune serum.
      The endotoxin, on the other hand, is heat-stable, is formed in the later period
      of growth, and is not neutralized by the antiexotoxic serum. The exotoxin
      exhibits a specific affinity for the central nervous organs in the rabbit, giving
      rise to a characteristic lesion-mainly, hemorrhages, necroses, and possibly a
      perivascular infiltration in the gray matter of the upper spinal cord and
      medulla. The endotoxin exerts a typical action on the intestinal tract, producing
      edema, hemorrhages, necroses, and ulcerations, especially in the large intestine.
      In dysentery in man the intestinal lesions predominate, but in severe epidemics
      paralysis and neuritis have been observed (Osler(17)). These facts become
      specially significant from the standpoint of the serum therapy of bacillary
      dysentery. A potent antidysenteric serum should contain antibodies against the
      exotoxin as well as the endotoxin. That such a serum can be produced in horses
      has been experimentally demonstrated.

PMID- 19868387
TI  - THE CULTURAL DIFFERENTIATION OF BETA HEMOLYTIC STREPTOCOCCI OF HUMAN AND BOVINE
      ORIGIN.
AB  - None of the procedures described serves by itself to differentiate streptococci
      of human and bovine origin with certainty, though each of them serves as a strong
      presumptive test. Most strains fall easily into the human or bovine group by all
      the tests. Eliminating these from consideration we have left certain irregular
      strains listed in Table VII. See PDF for Structure Taking all characters into
      consideration we are inclined to regard Strains J-E7, Cheese 1, and Cheese 2 as
      undoubtedly of bovine origin. Strain J-MJ also is representative of a group of
      streptococci which Jones has found in milk and which is being further studied by
      him. There remains Strain J-C65 which for the present must be regarded as of
      doubtful origin.

PMID- 19868388
TI  - DAIRY INFECTION WITH STREPTOCOCCUS EPIDEMICUS.
AB  - A streptococcus epidemic of moderate extent and severity was characterized by
      clinical symptoms different from the usual septic sore throat, though the
      organism found was culturally Streptococcus epidemicus. The infection was traced
      to the milk from a single quarter of the udder of a cow in a dairy of 112 cows
      producing an otherwise excellent grade of raw milk. A number of the milkers on
      the dairy farm were found infected. It was impossible to trace the infection of
      the cow's udder to any one of the milkers, though such an infection seems
      probable since the streptococcus isolated from the cow was in every respect like
      streptococci isolated from patients and milkers, and different from those usually
      found in normal cows or cows with garget. Certain recommendations are made to
      safeguard producers of raw milk against the occurrence of such epidemics.

PMID- 19868389
TI  - THE EFFECTS OF INTRAVENOUS INJECTIONS OF DICHLOROETHYLSULFIDE IN RABBITS, WITH
      SPECIAL REFERENCE TO ITS LEUCOTOXIC ACTION.
AB  - 1. The lethal dose of dichloroethylsulfide (distilled from a German yellow cross
      shell), when injected intravenously into rabbits is from 0.005 to 0.01 gm. per
      kilo. 2. Rabbits dying within 24 hours showed extensive hemorrhages, and edema of
      the lungs. 3. Severe lesions of the intestinal tract were present in about one
      third of the rabbits. 4. Dichloroethylsulfide injected intravenously is
      specifically poisonous for the hematopoietic tissues. Severe lesions are caused
      in the bone marrow, and the number of circulating leucocytes is markedly
      deminished. In animals surviving the injection regeneration occurs. The granular
      cells of the bone marrow seem to be more sensitive than the lymphoid cells and
      the erythrocytes. 5. The effect upon the blood and hematopoietic tissues is not
      due to the admixture of nitrobenzene or chlorobenzene in the shell filling.
      Injection of these substances in animals in amounts many times greater than the
      total dose of dichloroethylsulfide used produced no changes in the blood picture,
      and the subsequent injection of dichloroethylsulfide free from these solvents
      produced a typical reaction.

PMID- 19868390
TI  - FUNGOUS DEVELOPMENTAL GROWTH FORMS OF BACILLUS INFLUENZAE : A PRELIMINARY NOTE.
AB  - It has been found that three different strains of an organism supposed to be
      Bacillus influenzae will, under certain conditions, abandon the usual bacillary
      form and grow as a frank fungus, morphologically of the Discomyces type. Under
      other conditions they show less modification, the most striking feature then
      being the production of conidiospores, bodies of a type not found in true
      bacteria. That this organism may not be the true Pfeiffer bacillus is
      conceivable, of course, but considering the source, morphology, ordinary cultural
      characteristics, and the poison production of the one strain tested, we consider
      this highly improbable. Further, we are confident that the cultures do not
      contain any contaminating organisms, as may be suggested. In short, we believe
      that we have been dealing solely with the true Pfeiffer bacillus. While these
      observations are of considerable interest as a contribution to the biology of the
      bacteria of this general type it cannot, of course, be predicted that they will
      prove to be of any significance as regards the true causative agent of epidemic
      influenza. Experimental work with this organism, apparently negative so far as
      reproducing true clinical influenza is concerned, has been carried out with the
      bacillary form exclusively. It may be found that its physiological capabilities
      in another phase are essentially different. This is a general biological law and
      there is no evident reason why it should not hold true here. It remains to be
      determined whether the relatively high, complex forms described have any relation
      to those that occur while the organism lives among other organisms on the
      respiratory mucosa or acts as a tissue invader. While it seems improbable that
      they should develop in the animal body, that is while the organism is living as a
      parasite, it is at least possible that the bacillus may, under some conditions,
      undergo some analogous or at least similarly radical modification. If this
      supposition is true its cultivability might well be quite different from that of
      its bacillary phase, in which event it might be present in abundance and yet not
      be found in ordinary cultures or be recognizable in films. But the more important
      problem would appear to be whether it can assume a simpler phase. If, as some
      believe, some of the infectious bacteria and fungi can do this, whether it be as
      minute, filter-passing, formed elements or as a more or less amorphous ("sym
      plastic,"(16) "crytoplasmic,"(15)) substance, an organism that is capable of as
      remarkable a range of morphological development upward might well go to the other
      extreme from the mean, bacillary stage. Whether or not this occurs and if so
      under what conditions are questions that deserve through investigation.

PMID- 19868391
TI  - MYCOSIS OF THE BOVINE FETAL MEMBRANES DUE TO A MOULD OF THE GENUS MUCOR.
AB  - A mucor, closely resembling Lichtheim's Mucor rhizopodiformis, was isolated from
      the diseased chorion of a cow and from the lungs and digestive tract of the
      fetus. No other microorganisms were detected. The mucor was demonstrated in
      teased preparations from the fresh cotyledons as well as in sections of tissues
      suitably hardened. It produced focal lesions in rabbits following the intravenous
      injection of spores. The condition of the amniotic fluid and the contents of the
      rumen of the fetus justify the inference that premature expulsion was impending.

PMID- 19868392
TI  - EXPERIMENTS ON THE NASAL ROUTE OF INFECTION IN POLIOMYELITIS.
AB  - 1. The experiments given in this paper, notwithstanding their seeming diversity,
      relate to the conditions underlying the states of susceptibility and
      refractoriness to infection with the virus of poliomyelitis applied to the nasal
      mucosa. 2. Certain monkeys are highly refractory to inoculation via the nares
      with the virus of poliomyelitis, apparently in virtue of a power possessed by the
      nasal mucous membrane to destroy or otherwise render ineffective the virus
      applied to it. 3. This property of the nasal mucosa appears to be distinct from
      any specific protective substance active upon the virus which may occur in the
      blood. 4. An effective nasal mucous membrane prevents the passage of the
      energetically applied virus to the brain and spinal cord. 5. The virus of
      poliomyelitis energetically applied to the nasal mucosa will survive for an
      undetermined period of time upon an ineffective, but for a relatively brief
      period of time upon an effective membrane. 6. The protective power possessed by
      the nasal mucosa is not in itself adequate to prevent infection with the virus
      introduced upon it, since slight injury to such independent structures as the
      meningeal-choroid plexus complex favors the passage of the virus from the nose to
      the central nervous organs. 7. The normal nasal mucosa is, therefore, an
      invaluable defense against infection with the virus of poliomyelitis; and the
      number of healthy and chronic carriers of the virus is probably determined and
      kept down through the protective activities of this membrane. 8. Antiseptic
      chemicals applied to the nasal mucosa upon which the virus has been deposited
      exhibit no great protective action and are of doubtful value. Indeed, it is not
      impossible that to the extent to which they may affect unfavorably the
      destructive properties of the nasal mucosa, they may be even objectionable. 9.
      Infection with the virus of poliomyelitis applied to the nasal mucosa under
      conditions favorable to the extension to the central nervous organs and
      multiplication there may be blocked or prevented by the injection of
      poliomyelitic immune serum into the blood. While the exact manner and site of
      attack of the immune serum upon the virus is somewhat conjectural, when all the
      available data are considered it seems probable that the meeting place of the
      virus and immune serum is in the subarachnoid space.

PMID- 19868393
TI  - ETIOLOGY OF YELLOW FEVER : X. COMPARATIVE IMMUNOLOGICAL STUDIES ON LEPTOSPIRA
      ICTEROIDES AND LEPTOSPIRA ICTEROHAEMOORRHAGIAE.
AB  - It has been previously reported that a filterable microorganism belonging to the
      genus Leptospira has been recovered from the blood or organs of human beings
      suffering from the disease known as yellow fever in Guayaquil, and that the
      organism, which has been termed Leptospira icteroides, induces in certain
      experimental animals the characteristic symptoms and lesions observed in the
      patients from whom it was isolated. It has also been previously shown that the
      serum from patients recovering from an attack of yellow fever in Guayaquil had
      the power to agglutinate and dissolve the organism when introduced into the
      peritoneal cavity of a normal guinea pig (Pfeiffer phenomenon). Moreover, the
      guinea pigs which had once been inoculated with the blood of yellow fever
      patients without succumbing to the infection, notwithstanding the fact that they
      had shown a definite febrile reaction after 4 to 5 days, were found to be
      refractory to a subsequent inoculation of a culture of Leptospira icteroides All
      these observations pointed to the possible relation of this organism to the
      disease known as yellow fever in Guayaquil. The demonstration of the
      filterability of the organism and the transmission of the infection with the same
      organism by Stegomyia calopus have further strengthened the probable etiological
      significance of the organism in yellow fever. It was by no means a simple problem
      to determine the relation existing between Leptospira icteroides and Leptospira
      icterohaemorrhagiae. An experiment reported in a previous paper seemed to justify
      the view that the two leptospiras are closely related but not identical, yet it
      was necessary to exhaust various other modes of differentiation before the
      distinction between them was firmly established. The present paper continues this
      phase of the inquiry in further detail. There have been taken up here the
      phenomena of agglutination, the reaction of Pfeiffer, complement fixation, the
      protective properties of various monovalent and polyvalent immune sera, and
      active immunity. As the result of experiments in connection with these immunity
      phenomena the following data are presented. Monovalent immune sera prepared by
      several successive injections in an animal naturally refractory to Leptospira
      icteroides possess the power to agglutinate in vitro not only the homologous
      strains, but also all other strains of icteroides tested. On the other hand, a
      slight effect, or none at all, has been observed when these immune sera have been
      mixed in vitro with various strains of Leptospira icterohaemorrhagiae. A similar
      relation exists between the monovalent anti-icterohaemorrhagiae sera and the
      various strains of Leptospira icteroides; that is, there is a slight
      agglutinating effect in some instances upon the icteroides strains, but it is
      never so strong as that occurring in tests against the icterohaehagiae strains.
      The Pfeiffer reaction gave a sharper differentiation between the two groups, for
      in most instances the phenomenon was specific for the group. There were
      occasional doubtful reactions, but not enough to warrant a confusion of the two
      groups. Polyvalent immune sera, one specific for icteroides, and the other for
      icterohaemorrhagiae, showed a high titer of neutralizing power for the cultures
      of the homologous groups. It was found, however, that the action of the sera is
      by no means absolutely specific, because the injection of a sufficient amount of
      the anti-icteroides serum apparently prevented a fatal outcome in a guinea pig
      inoculated with multiple minimum lethal doses of a culture of Leptospira
      icterohaemorrhagiae, and vice versa. The specificity of the serum was
      demonstrated only when it was used in smaller quantities. More or less
      specificity was shown by the complement fixation reaction, but it was not
      absolute. Weak fixation occurred when the anti-icteroides serum was mixed with
      one or the other of the icterohaemorrhagiae strains and vice versa, and strong
      fixation occurred only when the antiserum was mixed with one of the icteroides
      strains. The question naturally arises whether or not this apparent specificity
      is due to the homology of the serum and not altogether to a difference in genus
      of the strains. In other words, it is justifiable to question whether all these
      variations in the degree of intensity of the reaction are not due to strain
      variations of the same genus. This question is not finally settled by the present
      investigation, in which only four icteroides and nine icterohaemorrhagiae strains
      have been carefully studied. Nevertheless, on the basis of the findings with
      these thirteen strains, it seems probable that Leptospira icteroides and
      Leptospira icterohaemorrhagiae are closely allied but are nevertheless distinct
      in their immunological reactions. Perhaps the difference between the two may
      amount to that between subspecies or races. It has been pointed out earlier that
      the pathogenicity of the two is also distinct, inasmuch as icteroides produces
      chiefly icterus and nephritis and icterohaemorrhagiae hemorrhage and nephritis,
      the icterus being less and the hemorrhage more prominent in the evolution of the
      latter infection. In the study of active immunity-exclusive of vaccination
      difficulty has been experienced in the evaluation of the results, owing to the
      existence of natural resistance to infection among guinea pigs. A guinea pig may
      recover from the inoculation of Leptospira icteroides and then resist a
      subsequent inoculation with a virulent strain of Leptospira icterohaemorrhagiae,
      a condition simulating that brought about by the identity of the two organisms.
      However, the refractoriness of such an animal to icterohaemorrhagiae may be due
      to its natural immunity to it. In the present study, therefore, only those guinea
      pigs were selected which had reacted typically-though in mild degree -to the
      icteroides infection, in order to determine whether they were subsequently immune
      to the inoculation of icterohaemorrhagiae. Indeed, by this mode of
      experimentation it was found that the guinea pigs which had once passed through
      an attack of the icteroides infection were absolutely immune to a second
      infection with the same organism but reacted severely and sometimes fatally to a
      later inoculation of icterohaemorrhagiae. Although there were a number of
      instances in which a previous infection with icteroides did not confer any
      perceptible immunity upon the guinea pigs against icterohaemorrhagiae, another
      group of guinea pigs showed a considerable resistance to the icterohaemorrhagiae
      infection as compared with those which had never been inoculated with icteroides.
      There is not much doubt, therefore, that an icteroides attack brings about, in
      some instances at least, a certain degree of resistance to the
      icterohaemorrhagiae infection. Hence the study of the phenomena of active
      immunity strongly indicates that icteroides is closely related immunologically to
      icterohaemorrhagiae.

PMID- 19868394
TI  - ETIOLOGY OF YELLOW FEVER : XI. SERUM TREATMENT OF ANIMALS INFECTED WITH
      LEPTOSPIRA ICTEROIDES.
AB  - The use ot a polyvalent immune serum ot nign potency in tne treatment of an
      experimental infection of guinea pigs with Leptospira icteroides was found to be
      of definite advantage in checking the progress of the infection. When
      administered during the period of incubation the serum was found capable of
      completely preventing the development of the disease, although on subsequent
      examination hemorrhagic lesions of greater or less number and extent were found
      in the lungs of the guinea pigs which survived. Moreover, the serum modified the
      course of the disease and when used in the early stages of infection prevented a
      fatal outcome. Employed at a later stage, however, when jaundice and nephritis
      had been present for several days and the animal was near collapse, the serum had
      no perceptible beneficial effect. This was, of course, to be expected in view of
      the incidence of various pathological phases of this disease-nephritis,
      hepatitis, and other toxic symptoms in succession. In man the clinical
      manifestations are more gradual and distinct than in the guinea pig, yet the
      yellow fever patient whose temperature is sub-normal, and who has reached the
      stage of hemorrhages from the gums, nose, stomach, and intestines, and of uremia
      and cholemia, would seem to have little or no chance of deriving benefit from the
      use of a specific immune serum. This latter assumption would probably hold
      irrespective of the relation which Leptospira icteroides proves to have to the
      etiology of yellow fever.

PMID- 19868395
TI  - THE STERILIZATION OF LIPOVACCINES.
AB  - Pneumococcus lipovacdne confers a definite protection against pneumococcus
      infection in mice. The protective quality is not destroyed, and apparently is not
      greatly diminished, by heating to 130 degrees C. for 3 hours or 120 degrees C.
      for 12 hours. Typhoid lipovaccine gives rise to the formation of agglutinins in
      rabbits but to a lesser degree than saline suspensions. The antigenic qualities
      of the typhoid lipovaccine are greatly injured by heating to 130 degrees C. for 3
      hours.

PMID- 19868396
TI  - COAGULATION IN EMBRYONIC BLOOD.
AB  - 1. In pig embryos of 100 to 270 mm. the average coagulation time of the blood was
      found to be about 23 minutes. This represents a coagulation time six to eight
      times greater than that obtained for the adult. 2. The first evidence of
      coagulation in the blood of these embryos consisted in the appearance of small
      masses of fibrin deposited almost invariably at the side of the test-tube. The
      ensuing coagulum was, as a rule, in the nature of a sliding clot, never attaining
      any marked degree of density or firmness. 3. In an analysis of the possible
      factors involved in this greater coagulation time of embryonic blood, it was
      found that numerically the blood platelets varied from 415,000 to 800,000 per
      c.mm., a content not differing in any significant degree from that of the adult,
      in which the average was found to be about 588,000 with a variation from 544,000
      to 932,000. 4. The addition of platelet material obtained from adult pig blood
      reduced the coagulation time for embryonic blood to an average of 8.4 minutes, a
      decrease of 75 per cent. 5. The addition of two drops of 0.5 per cent calcium
      chloride reduced the coagulation time for embryonic blood to an average of 10.3
      minutes, a reduction of over 50 per cent. 6. The addition of tissue extract to
      embryonic blood reduced the coagulation time to an average of 3.7 minutes, a time
      essentially equivalent to that obtained for adult blood. The clot was of a much
      firmer character than that obtained either in the normal coagulation or in the
      calcium experiments. 7. Chemical analysis demonstrated a calcium content in
      embryonic blood in excess of that of the adult, in the proportion of 7 : 5. 8. In
      view of the results indicated above, it became evident that the calcium in
      embryonic blood must be present in some combined form. This conclusion is
      supported by experiments in which barium and magnesium brought about a reduction
      in coagulation time in non-oxalated embryonic blood, but did not have this effect
      when added to oxalated blood, indicating in the former case, on the basis of the
      specificity of calcium, a liberation of free calcium ions. With oxalated blood,
      it was also found that under certain conditions coagulation could be brought
      about by the addition of tissue extract. 9. That the fibrinogen content plays no
      important part in coagulation time is shown by the fact that whereas the maximum
      amount of fibrin obtained by defibrinating embryonic blood was about 12 per cent
      of that obtained from the adult, nevertheless upon the addition of tissue extract
      the coagulation time of embryonic blood becomes equivalent to that of the adult.
      10. The presence of bile was demonstrated in the circulating blood of these
      embryos. Since it was further demonstrated that by the addition of bile to adult
      blood conditions could be produced essentially identical with those of embryonic
      blood, and since in the preceding analysis of the factors involved in coagulation
      no significant differences could be demonstrated between the blood of the embryos
      and that of the adult other than the presence of bile in the former, the data
      justify the conclusion that the bile content in the circulation of 100 to 270 mm.
      pig embryos constitutes the primary factor accounting for the greater coagulation
      time in the blood of these embryos. A condition in embryonic blood in some
      respects comparable with that of icterus is also indicated. 11. In the calcium
      experiments the results are apparently due primarily to the introduction of
      calcium ions in excess of the amount which enters into chemical combination with
      the bile present. With tissue extract it appears that the free calcium ions
      essential for the initiation of coagulation must be liberated through some
      interaction with the constituents of bile. 12. The results of this study suggest
      that the normal coagulation of embryonic blood, as far as bile is concerned,
      involves a process comparable with that obtained after the addition of tissue
      extract or cephalin, but on a smaller scale. In the embryonic blood in vitro,
      through the gradual disintegration of cellular elements, a certain amount of
      tissue substance (cephalin (?)) is slowly set free in the plasma, neutralizing
      the bile and ultimately liberating a sufficient amount of calcium to bring about
      coagulation.

PMID- 19868397
TI  - CRESCENTIC BODIES IN AESTIVO-AUTUMNAL MALARIA; THEIR MIGRATION AND ATTACHMENT TO
      THE SURFACE OF THE RED CORPUSCLE.
AB  - 1. In pig embryos of 100 to 270 mn the average coagulation time of the blood was
      found to be about 23 minutes. This represents a coagulation time six to eight
      times greater than that obtained for the adult. 2. The first evidence of
      coagulation in the blood of these embryos consisted in the appearance of small
      masses of fibrin deposited almost invariably at the side of the test-tube. The
      ensuing coagulum was, as a rule, in the nature of a sliding clot, never attaining
      any marked degree of density or firmness. 3. In an analysis of the possible
      factors involved in this greater coagulation time of embryonic blood, it was
      found that numerically the blood platelets varied from 415,000 to 800,000 per
      c.mm., a content not differing in any significant degree from that of .the adult,
      in which the average was found to be about 588,000 with a variation from 544,000
      to 932,000. 4. The addition of platelet material obtained from adult pig blood
      reduced the coagulation time for embryonic blood to an average of 8.4 minutes, a
      decrease of 75 per cent. 5. The addition of two drops of 0.5 per cent calcium
      chloride reduced the coagulation time for embryonic blood to an average of 10.3
      minutes, a reduction of over 50 per cent. 6. The addition of tissue extract to
      embryonic blood reduced the coagulation time to an average of 3.7 minutes, a time
      essentially equivalent to that obtained for adult blood. The clot was of a much
      firmer character than that obtained either in the normal coagulation or in the
      calcium experiments. 7. Chemical analysis demonstrated a calcium content in embry
      onic blood in excess of that of the adult, in the proportion of 7: 5. 8. In view
      of the results indicated above, it became evident that the calcium in embryonic
      blood must be present in some combined form. This conclusion is supported by
      experiments in which barium and magnesium brought about a reduction in
      coagulation time in non-oxalated embryonic blood, but did not have this effect
      when added to oxalated blood, indicating in the former case, on the basis of the
      specificity of calcium, a liberation of free calcium ions. With oxa lated blood,
      it was also found that under certain conditions coagulation could be brought
      about by the addition of tissue extract. 9. That the fibrinogen content plays no
      important part in coagulation time is shown by the fact that whereas the maximum
      amount of fibrin obtained by defibrinating embryonic blood was about 12 per cent
      of that obtained from the adult, nevertheless upon the addition of tissue extract
      the coagulation time of embryonic blood becomes equivalent to that of the adult.
      10. The presence of bile was demonstrated in the circulating blood of these
      embryos. Since it was further demonstrated that by the addition of bile to adult
      blood conditions could be produced essentially identical with those of embryonic
      blood, and since in the preceding analysis of the factors involved in coagulation
      no significant differences could be demonstrated between the blood of the embryos
      and that of the adult other than the presence of bile in the former, the data
      justify the conclusion that the bile content in the circulation of 100 to 270 mm.
      pig embryos constitutes the primary factor accounting for the greater coagulation
      time in the blood of these embryos. A condition in embryonic blood in some
      respects comparable with that of icterus is also indicated. 11. In the calcium
      experiments the results are apparently due primarily to the introduction of
      calcium ions in excess of the amount which enters into chemical combination with
      the bile present. With tissue extract it appears that the free calcium ions
      essential for the initiation of coagulation must be liberated through some
      interaction with the constituents of bile. 12. The results of this study suggest
      that the normal coagulation of embryonic blood, as far as bile is concerned,
      involves a process comparable with that obtained after the addition of tissue
      extract or cephalin, but on a smaller scale. In the embryonic blood in vitro,
      through the gradual disintegration of cellular elements, a certain amount of
      tissue substance (cephalin(?)) is slowly set free in the plasma, neutralizing the
      bile and ultimately liberating a sufficient amount of calcium to bring about
      coagulation.

PMID- 19868398
TI  - THE HEMIC BASOPHIL.
AB  - 1. The basophilic granule of blood and marrow cells does not show the brown color
      reaction with benzidine solutions that is characteristic of the neutrophilic and
      eosinophilic granules. It differs from these types also in other important
      microchemical and physical particulars. 2. The hemic basophil which bears these
      granules is peculiar from a purely cytological standpoint, while physiologically
      it appears to be devoid of any functional activity comparable with that of the
      other granulocytes. 3. The peculiarities exhibited seem in every instance, at
      least for mammalian blood, best explained as evidence that the basophil is a
      degenerated or degenerating cell. It is probably derived from the eosinophilic
      cells and perhaps in rare cases from those of neutrophilic type.

PMID- 19868399
TI  - PNEUMOCOCCUS CULTURES IN WHOLE FRESH BLOOD : I. THE RETARDATIVE EFFECT OF THE
      BLOOD OF IMMUNE ANIMALS AND THE MECHANISM OF THE PHENOMENON.
AB  - 1. It has been shown that the whole uncoagulated blood of immune animals is not
      as highly pneumococcidal in vitro, as has been claimed by others. 2. Cultures of
      pneumococci in the fresh whole blood of immune animals, as compared with cultures
      in the blood of susceptible animals, show a greatly prolonged latent period, and,
      in a general way, the relative lengths of the latent periods of the cultures
      correspond to the relative resistances of the animals to infection by these
      organisms. 3. The blood of animals artificially immunized, both actively and
      passively, retards the growth of pneumococci in the same manner as the blood of
      naturally immune animals. 4. Microscopic examination of cultures of pneumococci
      in immune blood reveals chain formation, growth in clumps, and phagocytosis of
      the organisms by the polynuclear cells. It also shows that growth occurs first in
      the free serum, the clot being invaded later. 5. The retardation of
      multiplication depends on two factors, opsonization of the pneumococci by the
      immune serum and phagocytosis of the organisms by the polynuclear cells; growth
      readily occurs when either agent is absent. 6. Pneumococci multiply in
      defibrinated immune blood because few phagocytes are present after defibrination.
      7. Pneumococci grow in the most potent immune blood after mechanical destruction
      of the white cells. 8. It has not been shown that immune blood does not kill a
      certain number of the pneumococci with which it is inoculated, but the tentative
      conclusion has been arrived at that no killing occurs since none of the tests
      became sterile during the course of our experiments.

PMID- 19868400
TI  - EXPERIMENTS ON THE PRODUCTION OF SPECIFIC ANTISERA FOR INFECTIONS OF UNKNOWN
      CAUSE : III. THE EFFECTS OF A SERUM PRECIPITIN ON ANIMALS OF THE SPECIES
      FURNISHING THE PRECIPITINOGEN.
AB  - There is present in serum of high precipitin titer, produced by the repeated
      injection of rabbits with the blood-free serum of guinea pigs or dogs, a
      principle highly toxic for animals of the species furnishing the antigen.
      Intravenously the serum causes severe shock, and even sudden death, while locally
      it gives rise to acute inflammatory changes and profuse capillary hemorrhages.
      The complete removal of hemolysins and hemagglutinins from the serum by exposing
      it repeatedly to washed red cells lessens its toxicity to only a slight degree
      and one obviously dependent on these elements; while the further removal of
      precipitin by specific precipitation in vitro has no detoxifying effect whatever.
      Whether the toxic principle is a hitherto unrecognized antibody or perhaps a
      toxic product of the interaction of precipitin and precipitinogen,-one formed as
      readily in the test-tube as in the animal body,-remains to be determined. The
      symptoms of guinea pigs and dogs given an intravenous injection of treated or
      untreated serum markedly resemble those of anaphylaxis, but our attempts at
      desensitization have been unsuccessful. The local lesion in guinea pigs is more
      severe than that of the Arthus phenomenon. But these differences from anaphylaxis
      may, of course, be dependent merely on differing proportions of constituents that
      are themselves, as yet, scarcely apprehended. Our observations, as here summed
      up, were made with a practical point in mind, and as regards this point they are
      of a discouraging nature. In papers already published it has been shown that sera
      specifically effective against infections of which the excitant is unknown can in
      some cases be obtained by using infected tissue itself as antigen. Such sera
      must, of course, be deprived of antibodies injurious to tissue, prior to their
      employment in the animal body; and this was successfully accomplished in our
      early experiments by exhaustion with washed red cells. The purpose of the present
      work was to determine whether serum used as antigen gives rise to injurious
      principles in the antiserum. For the serum of infected individuals would in many
      diseases form a convenient antigen. It is evident that injurious principles
      result from its use, and that they are not removed from the antiserum when the
      latter is exhausted with red cells and its precipitin removed by specific
      precipitation, nor can their action be nullified by desensitization as carried
      out in anaphylaxis. Unless the obstacle of their presence is in some way overcome
      the body fluids of infected human beings cannot be practically utilized for the
      production of antiserum. In test animals the difficulty is not so grave. For we
      have found that the toxic antiserum produces no enduring lesions when it is
      administered intravenously in non-lethal doses.

PMID- 19868401
TI  - DETERIORATION OF CRYSTALLINE STROPHANTHIN IN AQUEOUS SOLUTION : ITS RELATION TO
      HYDROGEN ION CONCENTRATION AND A METHOD FOR ITS PREVENTION.
AB  - 1. Many of the glass containers commonly used in the laboratory, and most of the
      glass ampules employed in marketing sterile solutions for hypodermic or
      intravenous medication, yield sufficient alkali on autoclaving, to change the
      reaction of distilled water from pH 6.0 to pH 9.0. 2. This increase in alkalinity
      is sufficient to render biologically inert and partially to decompose aqueous
      solutions of crystalline strophanthin in the concentration ordinarily employed in
      the clinic. 3. It is suggested that for clinical use crystalline strophanthin be
      dissolved in 0.02 M standard phosphate solution at pH 7.0, and marketed in hard
      glass ampules, thereby insuring stability of reaction with preservation of
      biologic activity. 4. It should be borne in mind, both by laboratory worker and
      pharmacist, that the alkali yielded, on heating, by soft glass containers may be
      responsible for a considerable alteration in the hydrogen ion concentration of
      their contents.

PMID- 19868402
TI  - GIANT CENTROSPHERES IN DEGENERATING MESENCHYME CELLS OF TISSUE CULTURES.
AB  - 1. Degenerating mesenchyme cells in tissue cultures cultivated in various
      modifications of Locke's solution often have giant centrospheres. 2. These giant
      centrospheres develop gradually around the centriole and in their most complete
      condition consist of centriole, medullary zone, and cortical zone. 3. Preceding
      the appearance of the centrosphere the centriole is surrounded by degeneration
      granules or granules and vacuoles, and as the centrosphere develops these are
      forced first to the periphery of the medullary zone and latter, when it develops,
      to the periphery of the cortical zone. 4. The mitochondria become orientated
      about the centriole and centrosphere, at first more or less radially, later
      concentrically. They change from threads to rods and granules. 5. The giant
      centrospheres and cancer cell inclusions (Plimmer's bodies, etc.) are identical.

PMID- 19868403
TI  - THE ORMATION OF VACUOLES DUE TO BACILLUS TYPHOSUS IN THE CELLS OF TISSUE CULTURES
      OF THE INTESTINE OF THE CHICK EMBRYO.
AB  - The introduction of Bacillus typhosus into the hanging drop of a tissue culture
      of the intestine of a chick embryo leads to the rapid vacuolation of the cells of
      the tissues which comprise the growth of the cultures. The cells of the
      connective tissue, the endodermal membrane, the mesothelium, and also the
      clasmatocytes exhibit the ability to ingest Bacillus typhosus in the cultures.

PMID- 19868404
TI  - APPEARANCE OF ISOAGGLUTININS IN INFANTS AND CHILDREN.
AB  - 1. The isoagglutination reaction of 131 infants and children from birth to
      10(1/2) years was examined by testing their serum and washed corpuscles
      microscopically against the serum and corpuscles of each of the four adult
      groups. 2. The grouping as present in adults is rarely present in blood from the
      umbilical cord. 3. At birth and during the 1st month of life isoagglutination is
      rarely present, but the percentage of infants in whom the isoagglutinin group is
      established increases with age, so that after 1 year the group is usually
      established, and after 2 years is always present as in adults. 4. The grouping is
      established in the corpuscles before it is established in the serum; i.e., the
      corpuscles acquire agglutinophilic receptors before the serum acquires
      agglutinin. Therefore, Group I is the first group to be formed and Group IV is
      the last. 5. The early grouping in the corpuscles before the group is established
      in the serum is liable to change by the acquisition of new receptors. 6. When the
      grouping has been established in both serum and corpuscles it does not change. 7.
      Isoagglutinins are present in mother's milk and the grouping is identical with
      that in the mother's blood. These agglutinins are probably not transmitted to the
      nursing infant through the milk. 8. On account of the differences between the
      agglutination reactions in the blood of mother and child it is not safe to
      transfuse an infant from its mother without making the preliminary tests.

PMID- 19868405
TI  - EFFECT OF FEEDING THE PINEAL BODY UPON THE DEVELOPMENT OF THE ALBINO RAT.
AB  - The pineal body of young calves was fed to albino rats beginning at the age of 3
      weeks and extending over periods of from 3 to 6 weeks. Four litters of rats were
      used. Of these, fourteen rats were fed the pineal powder and ten were used as
      control subjects. Observations in regard to developmental changes and microscopic
      examination of the endocrine glands and reproductive organs were made. The pineal
      fed rats of the first two litters remained somewhat smaller than their controls.
      The pineal-fed and control animals of Litters 3 and 4 showed no differences in
      development. Microscopic studies showed no differences between pineal-fed and
      control rats. We may therefore conclude that feeding the desiccated pineal body
      of young calves to young albino rats fails to produce any effect upon the early
      development of these animals.

PMID- 19868406
TI  - SOURCE AND SIGNIFICANCE OF STREPTOCOCCI IN MARKET MILK.
AB  - The principal source of streptococci in milk is the cow's udder. The udder
      streptococci fall into two broad groups; those of the larger group agree in
      cultural characters and agglutination affinities with mastitis streptococci; the
      smaller group is composed of low acid-producing streptococci. The streptococci of
      the latter group produce clear zones of hemolysis about surface and deep colonies
      in horse blood agar plates. They attack dextrose, lactose, saccharose, and
      maltose, but do not ferment raffinose, inulin, mannite, or salicin. Acid
      production in dextrose by the members of this group is about the same as that
      produced by human streptococci under the same conditions. The limiting hydrogen
      ion concentration for these pleomorphic udder streptococci in dextrose serum
      bouillon is within the limits of the limiting hydrogen ion concentration observed
      by Avery and Cullen for human streptococci. All the streptococci from the vagina,
      saliva, skin, and feces have been non-hemolytic. Those from the saliva form a
      heterogeneous aggregation in which individuals fermenting raffinose, inulin, and
      mannite predominate. From the skin a characteristic streptococcus has been found.
      It produces acid in dextrose, lactose, saccharose, maltose, raffinose, mannite,
      and salicin, but fails to acidulate media containing inulin. The fecal
      streptococci are characterized by the formation of large amounts of acid in
      dextrose, lactose, saccharose, maltose, raffinose, inulin, and salicin. Mannite
      is not fermented. Neither the fecal nor the skin streptococci have been isolated
      from the bottled milk with any great frequency.

PMID- 19868407
TI  - EXPERIMENTAL STUDIES ON DIABETES : SERIES I. PRODUCTION AND CONTROL OF DIABETES
      IN THE DOG. 1. GROSS ANATOMIC RELATIONS OF THE PANCREAS AND DIABETES.
AB  - 1. The injurious effects of excessive carbohydrate diet are demon strable in
      partially depancreatized dogs, in the same manner as in human patients. With
      severe diabetes there is rapid progress of emaciation and weakness and early
      death. 2. With milder diabetes, there is frequently a transitional state
      following operation, when the fate depends on the diet. If the tolerance is
      spared for a time, recovery sometimes occurs to such extent that diabetes cannot
      be produced by any kind or quantity of feeding, but only by removal of a small
      additional fragment of pancreatic tissue. The proper degree of carbohydrate
      overfeeding is important in this early period for producing the most useful type
      of diabetic animals; namely, those having good digestion and general health
      combined with a permanent lowering of assimilative power, like the condition of
      human patients. 3. In the early stage, glucose is more powerful than starch in
      producing diabetes, and animals which are progressing toward complete recovery on
      starch diet can be sent into hopeless diabetes by admix ture of glucose. The
      difference seems to be merely of the rate of absorption, and indicates that a
      rapid flood of carbohydrate is more injurious to the pancreatic function than a
      slow absorption. When ever permanent diabetes is present, so that complete
      recovery is impossible, starch brings on glycosuria more slowly than sugar, but
      just as surely. The difference in time in different cases amounts to days, weeks,
      or months. The clinical lesson from such experiments is that even if a patient
      becomes free from glycosuria on withdrawal of sugar only, nevertheless other
      foods should also be limited. 4. No significant differences were observed between
      the assimilation of different starches, or any extreme lowering of the
      carbohydrate tolerance by proteins, such as alleged by certain writers in
      connection with the "oatmeal cure." 5. Repair of traumatic inflammation and
      hypertrophy of the pancreas remnant have been mentioned incidentally as the basis
      of the early tendency to recovery, and also hydropic degeneration of Lang erhans
      islands as an accompaniment of the lowering of tolerance by excessive diet. These
      are believed to have their parallels in human cases, and are to be described more
      fully hereafter.

PMID- 19868408
TI  - EXPERIMENTAL STUDIES ON DIABETES : SERIES I. PRODUCTION AND CONTROL OF DIABETES
      IN THE DOG. 2. EFFECTS OF CARBOHYDRATE DIETS.
AB  - 1. The injurious effects of excessive carbohydrate diet are demonstrable in
      partially depancreatized dogs, in the same manner as in human patients. With
      severe diabetes there is rapid progress of emaciation and weakness and early
      death. 2. With milder diabetes, there is frequently a transitional state
      following operation, when the fate depends on the diet. If the tolerance is
      spared for a time, recovery sometimes occurs to such extent that diabetes cannot
      be produced by any kind or quantity of feeding, but only by removal of a small
      additional fragment of pancreatic tissue. The proper degree of carbohydrate
      overfeeding is important in this early period for producing the most useful type
      of diabetic animals; namely, those having good digestion and general health
      combined with a permanent lowering of assimilative power, like the condition of
      human patients. 3. In the early stage, glucose is more powerful than starch in
      producing diabetes, and animals which are progressing toward complete recovery on
      starch diet can be sent into hopeless diabetes by admixture of glucose. The
      difference seems to be merely of the rate of absorption, and indicates that a
      rapid flood of carbohydrate is more injurious to the pancreatic function than a
      slow absorption. Whenever permanent diabetes is present, so that complete
      recovery is impossible, starch brings on glycosuria more slowly than sugar, but
      just as surely. The difference in time in different cases amounts to days, weeks,
      or months. The clinical lesson from such experiments is that even if a patient
      becomes free from glycosuria on withdrawal of sugar only, nevertheless other
      foods should also be limited. 4. No significant differences were observed between
      the assimilation of different starches, or any extreme lowering of the
      carbohydrate tolerance by proteins, such as alleged by certain writers in
      connection with the "oatmeal cure". 5. Repair of traumatic inflammation and
      hypertrophy of the pancreas remnant have been mentioned incidentally as the basis
      of the early tendency to recovery, and also hydropic degeneration of Langerhans
      islands as an accompaniment of the lowering of tolerance by excessive diet. These
      are believed to have their parallels in human cases, and are to be described more
      fully hereafter.

PMID- 19868409
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : I. PRODUCTION OF PNEUMOCOCCUS LOBAR PNEUMONIA
      IN MONKEYS.
AB  - 1. Lobar pneumonia has been consistently produced in normal monkeys by the
      intratracheal injection of minute amounts of pneumococcus culture. 2. The disease
      produced has been shown to be clinically identical with lobar pneumonia in man.
      3. Lobar pneumonia has been produced in the monkey in one instance by
      experimental contact infection. 4. Normal monkeys inoculated in the nose and
      throat with large amounts of pneumococcus culture have failed to develop lobar
      pneumonia though carrying the organism in their mouths for at least a month. They
      have likewise failed to show any evidence of upper respiratory tract infection.
      5. Monkeys inoculated subcutaneously or intravenously with pneumococcus culture
      have in no instance developed pneumonia, but have either died of pneumococcus
      septicemia or recovered without localization of the infection in the lungs.

PMID- 19868410
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : II. PATHOLOGY AND PATHOGENESIS OF
      PNEUMOCOCCUS LOBAR PNEUMONIA IN MONKEYS.
AB  - Study of the pathology of pneumonia experimentally produced in monkeys by the
      intratracheal injection of pneumococcus has shown that it is identical with the
      pathology of lobar pneumonia in man. It has been found that the pneumococcus
      primarily invades the pulmonary tissue at some point or points in the portion of
      the lobe proximal to the hilum, that it spreads rapidly throughout the lobe by
      way of the perivascular, peribronchial, and septal interstitial tissue and
      lymphatics, quickly reaching the pleura, and that it invades the alveolar
      structure primarily by way of the alveolar walls, subsequently passing into the
      alveolar spaces simultaneously with the outpouring of exudate into the alveoli.
      It has been shown that the initial mode of invasion may be by direct penetration
      at one or more points into the walls of the larger bronchi near the hilum. The
      possibility that primary invasion may occur in terminal bronchioles, alveolar
      ducts, or alveoli of the parenchyma near the hilum has not been certainly
      excluded, though the evidence is against this supposition. In harmony with the
      mode of distribution of pneurnococci it has been found that the initial lesions
      of lobar pneumonia are of the interstitial framework of the lung, with respect
      both to the grosser framework and to the alveolar framework. Hepatization begins
      centrally and spreads toward the periphery and is a constantly progressive
      process. With the development of hepatization the conspicuous interstitial
      lesions of the earliest stages gradually diminish and are often largely masked
      when complete lobar consolidation has developed. Resolution is frequently
      accompanied by a varying degree of organization of the grosser framework of the
      lung. A variable amount of organization of the alveolar exudate also may occur.

PMID- 19868411
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : I. PRIMARY INFECTION IN THE TESTICLE.
AB  - A study was made of the infections produced in rabbits inoculated in the
      testicles with two strains of Treponema pallidum which had been carried in
      rabbits for several years. Infection resulted in all instances; the incubation
      period varied as a rule between 2 and 6 weeks and under properly chosen
      conditions could be reduced to approximately 3 weeks or less. The resulting
      infection pursued a typically cyclic or relapsing course which affected both the
      spirochetes and the associated lesions in the testicle. The spirochetes in the
      local lesions exhibited periodic changes less marked and less regular but
      identical in character with the changes which occur in the blood in cases of
      relapsing fever. The lesions in the testicle also showed periods of active
      development and quiescence or regression which followed closely upon the changes
      exhibited by the spirochetes. The specific reaction in the testicle showed
      considerable variation in the speed and sharpness with which successive phenomena
      occurred as well as in the character and extent of the processes themselves.
      These reactions were of two fundamental types. In one group of animals, the
      reaction was characterized by an intense cycle of acute exudation and
      infiltration with a lesser degree of proliferation, followed by crisis and
      subsequent recurrence of secondary cycles of proliferative reaction of a minor
      degree. In the other group of animals, the reaction was more chronic in character
      and consisted largely of infiltration and proliferation. The progress of the
      reaction was more gradual, and sharp alterations in its course were absent. The
      infection progressed by a succession of stages with slight and irregular
      remissions. In a third group of animals, the reaction was subacute, combining at
      the same time the processes of exudation, infiltration, and proliferation. The
      first cycle of reaction was fairly acute and terminated in a definite crisis with
      moderate regression which in turn was followed by recurrence and more or less
      pronounced secondary cycles of proliferation. In all cases of outspoken
      infection, there was diffuse involvement of testicle, tunic, epididymis, and
      cord, but as the infection progressed, the lesions underwent many
      transformations, so that a variety of lesions was formed from processes which in
      the beginning were of a common type. Eventually, the reaction became more
      irregular and the infection became centered in one or more foci which were
      commonly situated in the epididymis, tunics, scrotum, or mediastinum testis.
      These centers served as residual foci of infection. The duration of the
      testicular process was found to be very variable. In some animals, the entire
      reaction consisted of but a single sharp cycle, and the local infection was
      terminated by crisis within 4 to 6 weeks after inoculation. As a rule, the period
      of active infection was from 2 to 4 months, and quiescent or inactive lesions not
      infrequently lasted for from 4 to 6 months. In exceptional instances, local
      infection persisted for more than a year.

PMID- 19868412
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : III. SPONTANEOUS PNEUMONIA IN MONKEYS.
AB  - Spontaneous pneumonia occurred to a considerable extent among stock monkeys at
      the Army Medical School. This pneumonia occurred chiefly in the form of an
      epidemic outbreak shortly after the arrival of a large shipment of monkeys, and
      was shown to be due in large part to transmission of infection from monkey to
      monkey, either directly or indirectly. That spread of the epidemic was
      facilitated by overcrowding was indicated by the fact that in a subsequent
      shipment of monkeys, which were kept in pairs in separate cages and were not
      allowed to come into contact with the monkeys among which the epidemic occurred,
      no cases of spontaneous pneumonia developed. The close analogy between the
      epidemic of lobar pneumonia that occurred among the monkeys and similar epidemics
      of lobar pneumonia that occurred during the war among certain groups of newly
      drafted troops shortly after their arrival at camp is very striking, and would
      seem to indicate that pneumococcus pneumonia may become an epidemic disease among
      groups of susceptible individuals when they are assembled under conditions that
      facilitate the ready transfer of infection from individual to individual.
      Bacteriological examination showed the spontaneous pneumonia to be due in the
      great majority of cases to infection with Pneumococcus Type IV. Immunological
      classification of the strains of pneurnococci by cross-agglutination tests showed
      that the majority fell into two biological groups. Two cases were apparently
      caused by Streptococcus haemolyticus, two by Streptococcus viridans. The clinical
      course of spontaneous pneumococcus pneumonia in monkeys was characterized by
      sudden onset, high sustained temperature, leucocytosis, rapid respiration with
      expiratory grunt, cough, physical signs of consolidation, invasion of the blood
      by pneurnococci, and termination in death or recovery by crisis about the 7th to
      9th day. In a few instances the disease was complicated by acute fibrinopurulent
      pericarditis, by empyema, and by purulent meningitis. It was, therefore,
      clinically identical with lobar pneumonia experimentally produced in monkeys and
      with lobar pneumonia in man. Study of the pathology of spontaneous pneumococcus
      pneumonia in monkeys showed that it presented the characteristic picture of lobar
      pneumonia, both macroscopically and microscopically, and was in all respects
      comparable with the pathology of lobar pneumonia experimentally produced in
      monkeys and of lobar pneumonia in man.

PMID- 19868413
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : IV. RESULTS OF PROPHYLACTIC VACCINATION
      AGAINST PNEUMOCOCCUS PNEUMONIA IN MONKEYS.
AB  - 1. The subcutaneous inoculation of monkeys with Pneumococcus Type I vaccine in
      doses comparable with those employed in man does not protect them against
      subsequent attacks of Pneumococcus Type I pneumonia, either spontaneous or
      experimental. Furthermore, the occurrence of Pneumococcus Type IV pneumonia among
      monkeys that have been vaccinated with Pneumococcus Type I lipovaccine indicates
      that the vaccinated animals develop no cross-protection against other types of
      pneumonia. 2. Vaccination does, however, modify the course of the disease.
      Invasion of the blood stream by the pneumococcus in vaccinated animals is usually
      slight, and the proportion of recoveries is considerably higher for vaccinated
      than for unvaccinated monkeys. 3. Pneumococcus saline vaccine produces a greater
      amount of protective substance in the serum of the vaccinated animal than does
      pneumococcus lipovaccine and is probably, therefore, a better antigen. Both,
      however, fail to protect the animal against pneumococcus pneumonia. 4.
      Subcutaneous vaccination with pneumococcus vaccine gives definite protection
      against experimental pneumococcus septicemia. In other words, vaccination may
      induce a humoral immunity without protecting against intratracheal infection. 5.
      In view of the fact that monkeys are highly susceptible to pneumococcus
      infection, a strict analogy cannot be drawn between pneumococcus immunity in
      monkeys and pneumococcus immunity in man, since in the latter a considerable
      amount of resistance already exists, probably by reason of repeated exposure to
      pneumococcus infection.

PMID- 19868414
TI  - EXPERIMENTAL STUDIES ON DIABETES : SERIES I. PRODUCTION AND CONTROL OF DIABETES
      IN THE DOG. 3. EFFECTS OF PROTEIN DIETS.
AB  - No specific differences were observed between the glycosuric effects of different
      kinds of protein. Other incidental observations were noted in connection with the
      records of individual animals. General conclusions are deferred to the close of
      the series.

PMID- 19868415
TI  - EXPERIMENTAL STUDIES ON DIABETES : SERIES I. PRODUCTION AND CONTROL OF DIABETES
      IN THE DOG. 4. CONTROL OF EXPERIMENTAL DIABETES BY FASTING AND TOTAL DIETARY
      RESTRICTION.

PMID- 19868416
TI  - EXPERIMENTAL STUDIES ON DIABETES : SERIES I. PRODUCTION AND CONTROL OF DIABETES
      IN THE DOG. 5. VARIOUS FAILURES OF DIETETIC TREATMENT, AND THEIR CAUSES.
AB  - 1. Practically every detail of clinical diabetes can be reproduced in partially
      depancreatized animals. The resemblance is made still more exact by the
      susceptibility of such dogs to acidosis and coma, as will be shown in later
      papers, and also by the similarity of the anatomic changes in the islands of
      Langerhans. These animals are therefore useful test objects for a therapeutic
      investigation. 2. These animals at first show considerable tendency to regain
      assimilation, comparable to that in the early stages of most human cases of
      diabetes; and in some instances they recover so as to be able to endure any
      degree or duration of carbohydrate feeding and can be made diabetic only by
      removal of additional pancreatic tissue. Similar recovery in some human cases,
      especially after acute pancreatitis, is a probability. This recuperative tendency
      can be negatived by overfeeding, even without glycosuria. With duration of the
      diabetes the power of recuperation diminishes and practically disappears in dogs
      as in human patients. 3. In the absence of progressive pancreatitis or other
      extraneous causes, these dogs show no inherent downward tendency in their
      assimilation. This conclusion rests upon observations as long as 6 years from the
      first pancreas operation and 3 years of known diabetes. This absence of inherent
      progressiveness is what should naturally be expected in animals with simple
      resection of part of an organ, and serves further to fit them for accurate
      feeding experiments. 4. Every detail of the downward progress of human patients
      on various diets is reproduced in such animals. They lose assimilation and die
      most rapidly on diets rich in carbohydrate, and less rapidly on excess of other
      foods. The differences between sugar and starch, and between starch and protein,
      seem to be only those of degree and time rather than anything absolute. The
      important point is that, granting the absence of spontaneous downward tendencies
      as stated, all the different kinds and degrees of downward progress in the
      records of animals in this and the preceding paper are purely the results of
      overstrain of the internal pancreatic function by excess of food. 5. Varying
      degrees of success and failure in the dietetic control of diabetes are also
      illustrated. The benefit of the classical treatment by exclusion of preformed
      carbohydrate and limitation of protein is confirmed, in the prolongation of life
      and well-being to some extent in nearly all cases and perhaps indefinitely in
      some of the mildest cases. In the great majority of cases such a therapeutic
      result is not permanent, and downward progress is finally observed if the
      observations are continued long enough. In most of these cases life, strength,
      and assimilation can be preserved for a much longer time by a degree of
      undernutrition suited to the severity of the diabetes, and accomplished by
      limitation of fat in the diet. The permanence of such control is supported by the
      unimpaired or rising assimilation in experiments of 1 to 1(3/4) years duration,
      but still longer observations would be desirable. Diabetes of great severity is
      controllable only by correspondingly radical undernutrition. In still more severe
      cases glycosuria can be abolished only by a degree of undernutrition which
      entails final death from inanition. In the most severe cases glycosuria cannot be
      stopped, evidently because the assimilative power is too low to dispose of even
      the minimum supply of food materials; namely, that derived from the body stores
      in fasting. 6. A claim of saving every patient, no matter how near death, would
      be a preposterous one for any remedy in any disease, and the animal experiments
      do not support such a claim for diabetes. Also it is unreasonable to expect the
      actual cure of an organic deficiency by diet, and the diet treatment in animals
      just as in patients generally represents the sparing rather than the restoration
      of the weakened function. The basis of the belief in the inherently progressive
      tendency of severe cases of clinical diabetes is shaken by the exact reproduction
      of such case histories by diet in animals which are free from spontaneous
      downward tendencies; but there is still lack of a sufficient number of patients
      treated on the principle of relief of the total metabolic burden to demonstrate
      the absence of such inherent progressiveness in human diabetes. As described
      elsewhere, the principle mentioned has given encouraging results in proportion as
      it has received actual application in practice. The clinical problem requires the
      same prolonged careful control of all discoverable symptoms as in animals, and
      cases too severe for such control, or complicated with infections, violations of
      diet, etc., are on the same plane as animals in which a similar condition has
      been produced. Some proportion of cases, especially in young persons, will be
      found suitable for accurate determination of the question of whether all or most
      cases of severe diabetes are inevitably progressive and hopeless, and the writer
      looks forward to publishing such a series. Irrespective of the outcome, the
      raising of this question is justified by its importance. On the theoretical side,
      it involves both the general prognosis and the nature of the process underlying
      diabetes. On the practical side, it is already established that diet is at least
      the chief cause of downward progress, and it is important to eliminate this cause
      by avoiding the dietary injuries illustrated in the animal experiments.

PMID- 19868417
TI  - RELATION OF THE PORTAL BLOOD TO LIVER MAINTENANCE : A DEMONSTRATION OF LIVER
      ATROPHY CONDITIONAL ON COMPENSATION.
AB  - The occlusion of portal branches to a part of the liver of the rabbit leads to a
      progressive and ultimately complete atrophy of the parenchyma in the region
      deprived of portal blood, and to hypertrophy of the rest of the hepatic tissue
      which receives such blood in excess. Three-fourths of the liver may thus be
      reduced to a fibrous tag within 2 months, while the remaining fourth attains the
      bulk of the entire original organ. The atrophy is simple, unaccompanied by
      obvious degenerative changes or by any connective tissue replacement. More
      important, it is conditional in nature, failing to progress when the bile duct
      from the proliferating tissue is ligated and its hypertrophy checked in this way.
      There are indications in the literature that an atrophy conditional on
      hypertrophy, such as is here described, occurs in man after local portal
      occlusion. And some experiments in our laboratory, not yet completed, show
      definitely its occurrence in the dog. The changes take place slowly in the canine
      liver. After 3 months the tissue deprived of portal blood has diminished to about
      one-third of its original bulk. The conditional character of the atrophy is
      proven by its failure to occur to any similar degree in the absence of a
      compensating parenchyma, as when the portal stream is diverted from the whole
      liver by way of an Eck fistula. Is the atrophy functional? If so, its
      completeness would indicate that the liver has no essential activity-none on
      which its maintenance depends-that it is not intimately connected with substances
      derived from organs drained by the portal system. Observations on the rate of
      hypertrophy after local diversion of the portal stream and on the character of
      the bile secreted by the atrophic tissue may be taken to favor such a view. The
      hypertrophy is nearly, perhaps quite, as rapid as if the tissue deprived of
      portal blood had been removed from the body. The bile secreted from a liver mass
      far advanced in atrophy and competing with a large bulk of parenchyma that
      receives the entire portal stream is almost colorless and may give but a weak
      Pettenkofer reaction. Glycogen, on the other hand, is present in the atrophic
      cells in approximately the same amount and distribution as in the hypertrophic
      liver tissue of the same animal. The fact that a parenchymal shift follows local
      disturbances in the portal stream has a bearing on the cause of certain
      alterations in the shape of the normal liver that have been loosely attributed
      heretofore to pressure from the surrounding organs. It also has some interest in
      connection with pathological changes. Liver hypertrophy dependent on a preceding
      destruction has long been known to pathologists. Now a type of destruction
      dependent on compensatory hypertrophy must also be reckoned with. The occurrence
      of changes of the latter character will explain certain of the lesions observed
      in diseases that involve a disturbance of the portal flow to portions of the
      liver substance.

PMID- 19868418
TI  - EPIDEMIOLOGY OF BLACKHEAD IN TURKEYS UNDER APPROXIMATELY NATURAL CONDITIONS.
AB  - The foregoing experiments in outdoor, unprotected enclosures demonstrates the
      difficulties surrounding the rearing of turkeys. These are discussed from another
      view-point and to avoid repetition only a few outlying facts should be considered
      here. The occasional presence of coccidia, the presence of Heterakis papillosa in
      the ceca, the occurrence of cases of aspergillosis and of chicken-pox in
      incubator-bred birds which did not come in contact with other domesticated birds,
      except in a few cases with incubator-bred chickens, show clearly that turkeys are
      picking up from the ground material deposited by other birds. The agent of
      blackhead must come from the same sources. The field experiments show a steadily
      increasing concentration of the infection from 1917 to 1919, even though the
      ground had been ploughed and seeded before use. As a result, the various groups
      of turkeys became infected to a greater degree. The growth in the intensity of
      the disease may be in part ascribed to an accumulation on the soil of infectious
      agents during any given season after they had been introduced, but it is hardly
      acceptable as an explanation from season to season, when the soul was either
      virgin, as regards poultry yards, or ploughed deep and seeded before use. A more
      rational hypothesis is the gradual attraction of birds in larger numbers and
      greater variety on account of the food supply in the turkey enclosures and the
      more intensive cultivation of the land surrounding the laboratory and animal
      buildings since the beginning of the experiments in 1917. The intensity of the
      outbreaks due to the confining of young turkeys with birds over a year old which
      had been infected during the preceding year, or on ground previously occupied by
      them, was in all instances much greater than in the spontaneous outbreaks. The
      cases amounted to nearly 100 per cent of the exposed. On the other hand, the
      number of cases in the control flocks varied and was very low in some groups. It
      could have been kept down if the sick birds had been promptly removed and not
      permitted to recover on the same ground. However, the object of the experiment
      was not to suppress the disease, but to see to what extent it would develop. It
      is self-evident that the results obtained apply strictly only to that part of the
      country where the experiments were made. We have at present no means of knowing
      whether the sources of infection would become more numerous and concentrated with
      a higher mean annual temperature, or the reverse. Only by using incubator turkeys
      exclusively for such tests and eliminating the older turkeys and domesticated
      birds as carriers, can the miscellaneous, at present not controllable sources of
      the agents of this disease in different localities and the chances of successful
      rearing be determined.

PMID- 19868419
TI  - PRODUCTION OF FATAL BLACKHEAD IN TURKEYS BY FEEDING EMBRYONATED EGGS OF HETERAKIS
      PAPILLOSA.
AB  - In four experiments, three with young incubator turkeys and one with young
      incubator chickens, in which the feces of old turkeys from an infectious flock,
      kept at room temperature up to 5, 8, and 10 days, were fed, no infection
      resulted. In an experiment in which two of four young incubator turkeys used in
      one of the above experiments were fed embryonated eggs of Heterakis papillosa and
      feces of turkeys from an infectious flock both contracted blackhead. Two controls
      remained well. Later they were fed embryonated eggs of Heterakis papillosa and
      both contracted blackhead. In another experiment three incubator turkeys received
      embryonated eggs plus turkey feces from an infectious flock. All contracted
      blackhead. Three received embryonated eggs alone; all contracted blackhead. Three
      received turkey feces only; none contracted blackhead. Three controls received
      nothing; one showed blackhead lesions at the autopsy. In a final experiment three
      turkeys were fed cultures of feces from the ceca of diseased turkeys, three were
      fed cultures of feces of old turkeys from an infected flock, and three controls
      were fed nothing. None contracted blackhead. The cultures of feces were prepared
      precisely as were the earlier ones containing Heterakis eggs but without the
      latter. From these experiments it becomes evident that blackhead may be produced
      in healthy incubator-raised turkeys, reared in the open in an environment where
      blackhead occurs, but out of direct contact with old turkeys and other poultry,
      by feeding cultures of embryonated eggs of Heterakis papillosa, prepared by
      cutting up the worms in isotonic salt solution and incubating the suspension at
      room temperature. These very definite and clear-cut results outweigh any
      objections which may be raised against the use of turkeys which had been in
      earlier experiments and which came through such experiments without any signs of
      disease, or which came from control flocks in which spontaneous cases had
      occurred. The short time elapsing between feeding embryonated eggs and the first
      signs of disease made these experiments unusually impressive. It should be
      stated, furthermore, that from a precise individual record of all turkeys it was
      possible to select birds from control flocks in which the infection had either
      not appeared or was very low. All but two turkeys in flocks serving as sources of
      this material were killed at the close of the year. None at any time had shown
      symptoms of disease, and no scars or other abnormalities of ceca and liver were
      found. Furthermore, all other control birds and those in field experiments, with
      the exception of two reserved for breeding, were likewise killed. As a result of
      these autopsies, it was determined that of all birds in which symptoms of disease
      had not been recorded during life, none showed abnormalities or scars at autopsy.
      The protozoan factor in blackhead was probably disseminated when the first
      spontaneous cases occurred in the stock, unless it was present and made invasive
      by incubation in the cultures fed. This latter theory seems at present not
      acceptable because of the wholly negative outcome of Experiment 8. The production
      of acute blackhead by feeding embryonated eggs to turkeys in whose ceca adults of
      Heterakis papillosa are already present seems incomprehensible at first thought.
      A tentative explanation to be offered is that the worms when invading the ceca in
      large numbers break down the resistance of the bird which is able to protect
      itself against a few. This may account for the very irregular occurrence of cases
      in contact with older recovered birds on infected grounds. The role of Heterakis
      as a preliminary agent may also account for the continuing high mortality in
      turkeys in which the disease has been operating for so many generations to
      eliminate the most susceptible. It now seems highly probable that the turkey has
      become relatively resistant to the invasion of the protozoan parasite acting
      alone and that such invasion may require other agencies. Whether Heterakis
      papillosa is the only, or at any rate, the chief accessory agent or whether there
      are others, living or inert, which when ingested by the turkey assist in
      preparing the way for the destructive invasion of the walls of the ceca and the
      liver by Amoeba meleagridis is a question now open to solution by
      experimentation. The relation of common poultry to outbreaks of blackhead may be
      accounted for, at least in part, by the fact that they are hosts of Heterakis
      papillosa. How frequently they also carry Amoeba meleagridis remains to be
      determined. Since earlier communications have contained certain practical
      suggestions on the rearing of turkeys and the prevention of blackhead, it is not
      out of place here to point out that the additional information presented in this
      article simply emphasizes the suggestions already made. Turkeys should be raised
      in the incubator and brooder and kept away from older turkeys and poultry. The
      shelters should be moved from time to time to prevent a too concentrated
      infection of the soil with Heterakis ova. Inasmuch as the factors producing
      blackhead may be deposited by certain still undetermined birds on the wing,
      disease may be looked for at any time during the warm season. It is not, however,
      very readily transmitted, and in the experiments described elsewhere the
      mortality from spontaneous blackhead was low. The flock should be looked over as
      frequently as possible, and whenever a turkey begins to droop, it should be
      isolated and killed if the drooping continues over several days. If such turkeys
      are allowed to recover, they should not be returned to the young flock but kept
      with older, presumably infected birds. Such birds are entirely satisfactory as a
      source of eggs, since there is no evidence that the latter transmit the
      infection.

PMID- 19868420
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : V. ACTIVE IMMUNITY AGAINST EXPERIMENTAL
      PNEUMOCOCCUS PNEUMONIA IN MONKEYS FOLLOWING VACCINATION WITH LIVING CULTURES OF
      PNEUMOCOCCUS.
AB  - 1. The subcutaneous injection of small doses of living virulent Pneumococcus Type
      I stimulates in monkeys a degree of active immunity sufficient to protect them
      against experimental pneumococcus pneumonia of homologous type. 2. The
      subcutaneous injection of living avirulent Pneumococcus Type I, if administered
      in a sufficiently large dose, likewise renders the monkey immune to a subsequent
      pneumonia of homologous type. 3. Vaccination of monkeys with small doses of
      living virulent pneumococci may or may not be followed by a severe constitutional
      reaction, depending on the natural resistance of the individual. The severe
      reactions are caused by the development of a pneumococcus septicemia. which is
      either temporary, or leads to a fatal termination. The mild reactions are not
      accompanied by septicemia, and there are no symptoms other than a slight
      elevation of temperature and moderate leucocytosis. Vaccination with living
      avirulent pneumococci does not induce severe reactions and is not accompanied by
      pneumococcus septicemia. 4. Active immunity against pneumococcus pneumonia,
      produced by vaccination with living pneumococci, appears to be largely
      independent of the presence or absence of agglutinins and protective bodies in
      the serum of the monkey. 5. Vaccination with living cultures of Pneumococcus Type
      I confers against other types of pneumococci a certain amount of cross-immunity
      which, however, varies considerably with the individual monkey. 6. immunity
      against pneumococcus, like other forms of immunity, is a relative term, and
      depends upon the capacity of the individual for antibody production, the
      virulence of the invading microorganism, and the size of the dose injected.

PMID- 19868421
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : VI. ACTIVE IMMUNITY FOLLOWING EXPERIMENTAL
      PNEUMOCOCCUS PNEUMONIA IN MONKEYS.
AB  - 1. Experimental Pneumococcus Type I pneumonia in monkeys confers on them an
      immunity which protects them against subsequent infection with the homologous
      type of pneumococcus. The duration of this immunity has not been determined. 2. A
      certain amount of cross-immunity against the other fixed types of pneumococcus
      pneumonia may or may not be present following experimental Pneumococcus Type I
      pneumonia. The degree of cross-immunity is difficult to measure and probably
      varies widely with the individual monkey. 3. Experimental Pneumococcus Type IV
      pneumonia in monkeys confers slight if any protection against subsequent
      infection with the same, or with an homologous strain of Pneumococcus Type IV. 4.
      There is no evidence in monkeys of cross-immunity against Pneumococcus Type IV
      pneumonia following Pneumococcus Type I pneumonia; and conversely, Pneumococcus
      Type IV pneumonia confers no cross-immunity against Pneumococcus Type I
      pneumonia.

PMID- 19868422
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : II. PRIMARY INFECTION IN THE SCROTUM. PART
      1. REACTION TO INFECTION.

PMID- 19868423
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : II. PRIMARY INFECTION IN THE SCROTUM. PART
      2. SCROTAL LESIONS AND THE CHARACTER OF THE SCROTAL INFECTION.
AB  - From a study of the reaction to scrotal inoculation with Treponema pallidum in
      alarge series of rabbits, it was found that the specific reaction presented the
      following characteristics. In general, the reaction in the scrotum became
      apparent within 7 to 14 days after inoculation but was subject to considerable
      variation. The early reaction took the form of an edematous swelling and
      congestion associated with a new growth of vessels or of an infiltration with
      more or less proliferation of fixed tissue cells. These reactions were either
      confined to a small circumscribed area of the scrotum or were of a diffusely
      spreading character, and as the infection advanced, the infiltration and
      proliferation together with such secondary changes as exfoliation, necrosis, and
      ulceration became the most conspicuous features of the reaction. The course of
      the reaction in the scrotum was essentially the same as that in the testicle;
      that is, it was periodic in character and was marked by a phase of active
      progression followed by quiescence or regression and renewed activity. The
      scrotal reaction resembled that in the testicle also in the varying character of
      the reaction, appearing at times as a circumscribed focus of reaction and later
      becoming diffuse, or first as a diffuse reaction which subsequently became more
      localized. The lesions produced in consequence of this reaction were of two
      general types -one a circumscribed indurated granulomatous lesion closely
      resembling the human chancre, the other a diffuse infiltration more analogous to
      the secondary skin lesions of man. Both groups of lesions presented the greatest
      degree of individual variations and possessed no fixed status but were subject to
      frequent and marked transformations. After a period of from a few weeks to many
      months, the lesions in the scrotum disappeared spontaneously.

PMID- 19868424
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : III. LOCAL DISSEMINATION, LOCAL RECURRENCE,
      AND INVOLVEMENT OF REGIONAL LYMPHATICS.
AB  - From a study of the phenomena of the primary infection on the one hand, and the
      phenomena of local spread, or dissemination, on the other, it is seen that a
      multiplicity of lesions develops in the testicle and scrotum of the rabbit which
      have much the same characteristics irrespective of their origin. Some of these
      lesions are clearly recognizable as primary lesions or parts of a primary
      reaction to infection, while others are just as clearly the results of
      dissemination of the virus from a primary focus of infection or correspond with
      lesions which are commonly spoken of as secondary lesions. The effort to draw a
      sharp line of distinction between these two groups of lesions or between a
      primary and a secondary stage of infection in the rabbit, however, would be
      largely an arbitrary procedure. The fact is that the tissues of the scrotum and
      testicle of the rabbit constitute favorable surroundings for the localization and
      development of pallidum infections. Under ordinary circumstances, a large part of
      the reaction to infection which expresses itself in the formation of lesions
      recognizable by ordinary methods of examination takes place in these tissues.
      These lesions present certain broad and general characteristics without regard to
      whether they are primary or secondary in origin; the reaction is merely a
      reaction to a syphilitic infection which in either case may assume the most
      diverse character. Further, it would appear that in rabbits infected with such
      strains of Treponema pallidum as we have used, the virus is never confined to the
      area occupied by the so called primary lesion, or chancre, but always spreads and
      always gives rise to a regional adenopathy. There may be no lesions to indicate
      the progress of this dissemination, but an examination of the inguinal nodes
      shows that dissemination occurs very soon after inoculation, and a pallidum
      reaction may be detected in these glands even before infection can be recognized
      in the scrotum. Subsequently lesions develop in all parts of the scrotum and
      testicle, sometimes involving the entire testicle or scrotum, and at others,
      forming focalized lesions with an especial predilection for certain locations
      such as the epididymis, the mediastinum testis, the tunics, and the dorsal folds
      of the scrotum. In some instances, more or less continuous lesions form along the
      course of the perivascular lymphatics, suggesting that this is one path taken in
      the dissemination of the organism. It is probable, however, that lesions of a
      gross character develop more as a result of accumulation of spirochetes than of
      mere invasion of the lymphatics since they are not a constant accompaniment of
      the local infection, while invasion of the lymphatics and extension of the
      infection to the regional lymph nodes occur in all cases.

PMID- 19868425
TI  - HETEROTRANSPLANTATION OF THE THYROID GLAND.
AB  - 1. After transplantation of the thyroid of the guinea pig into rats there is a
      primary injury of the transplant, noticeable as early as 3, 4, and 5 days after
      transplantation. The tissue is less resistant, and it is preserved only under the
      best conditions. The number of mitoses is much diminished in the transplant, but
      they may appear even as late as 9 days after transplantation. This was also the
      latest time at which living tissue was found. Epithelium is best preserved in the
      neighborhood of growing fibroblastic tissue, and growing epithelium attracts
      fibroblasts. Few fibroblasts grow between acini, and they have a tendency to form
      fibrous tissue. Dense fibrous tissue compresses acini and contributes to their
      destruction. The vascularization of the graft is very poor, but some capillaries
      may penetrate between acini. The collection of lymphocytes around acini is only
      casual and may be found where fibroblasts are active and especially around the
      blood vessels in the capsule of the graft. On the whole, heterotransplanted
      tissue does not attract lymphocytes to any marked extent. Connective tissue and
      lymphocytes contribute only secondarily and to a minor extent to the destruction
      of the heterotransplant. 2. After transplantation of the thyroid of the rabbit
      into rats the last mitoses are found 9 days after transplantation; living acini
      are observed as late as 11 days after transplantation, and ducts of squamous
      epithelium even somewhat later. Different kinds of tissue seem to show a
      different degree of resistance to the action of heterotoxins. The difference in
      the resistance to heterotoxins corresponds to the difference in the resistance of
      various tissues to other kinds of injurious influences. The thyroid of rabbits
      is, on the whole, better preserved in the rat than the thyroid of the guinea pig;
      there is also more mitotic activity in the rabbit thyroid. The reaction of the
      tissues of the host towards heterotransplanted rabbit thyroid in principle is
      similar to the reaction to heterotransplanted guinea pig thyroid. 3. After
      transplantation of rabbit thyroid into guinea pigs well preserved thyroid is
      found not later than 8 days, while the last mitoses appear 6 days after
      transplantation. The number of mitoses is very small. The host tissues again
      behave in a manner characteristic of heterotransplantation. It is probable that
      slight infections and the presence of polynuclear leucocytes are responsible for
      the somewhat inferior results in this kind of heterotransplantation. 4. After
      transplantation of cat thyroidinto the rat, signs of degeneration in the
      transplanted acini appear at the end of the 1st week; they increase during the
      2nd week. The last well preserved acini are found at 14 days; a few degenerating
      acini are still visible as late as 18 days after transplantation. Almost all
      pieces are entirely necrotic in the 3rd week. Mitoses are only found 5, 9, 10,
      and 11 days after transplantation, and they are present in a limited number.
      There is a decided lack of good vascularization in the transplants; it is
      especially noticeable in the 2nd week after transplantation. Fibroblasts
      penetrate at various places between the acini and occasionally together with a
      few lymphocytes may destroy some of them. From the 9th day on the presence of
      fibrous tissue around the acini is noticeable. It compresses the acini and thus
      contributes to their destruction. Even the heterotransplanted thyroid exhibits a
      restraining influence on the connective tissue which is greater than that
      presented by dead material. The behavior of the lymphocytes towards
      heterotransplanted thyroid of the cat is similar to that towards other
      heterotransplanted thyroid.

PMID- 19868426
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : VII. TREATMENT OF EXPERIMENTAL PNEUMOCOCCUS
      TYPE I PNEUMONIA IN MONKEYS WITH TYPE I ANTIPNEUMOCOCCUS SERUM.
AB  - 1. In experimental Pneumococcus Type I pneumonia in monkeys the intravenous
      injection of Type I antipneumococcus serum exercises a specific therapeutic
      effect, frees the blood promptly and permanently from pneumococci, shortens the
      course of the disease, and greatly moderates its severity. Of five monkeys
      inoculated intratracheally with lethal doses of Pneumococcus Type I, all
      developed pneumonia, and all recovered following the administration of Type I
      antipneumococcus serum, while the controls died. 2. The earlier the serum is
      administered the shorter and less severe the pneumonia. Frequent injections are
      also an important factor in obtaining favorable results. When serum treatment is
      instituted late in the disease, the injections must usually be continued over a
      longer period of time in order to achieve success. 3. Normal horse serum exerts
      no beneficial effect whatever in experimental Pneumococcus Type I pneumonia.

PMID- 19868427
TI  - HOMEOTRANSPLANTATION AND AUTOTRANSPLANTATION OF THE SPLEEN IN RABBITS : III.
      FURTHER DATA ON GROWTH, PERMANENCE, EFFECT OF AGE, AND PARTIAL OR COMPLETE
      REMOVAL OF THE SPLEEN.
AB  - No instance of survival of spleen homeografts beyond the usual taking and
      persistence for 1 or 2 weeks common to most homeografts has been observed,
      although the possible advantages of consanguinity, age, and splenectomy were
      fully utilized. This is in sharp contrast to thyroid, sex gland, and adrenal
      cortex homeografts, with which one may expect 10 per cent to survive the 30 day
      period. It suggests that spleen is a stronger antigen and excites a greater
      degree of immunity more quickly. With autografts survival and growth are the
      rule, and failures are due to technical errors. Age is an important factor in the
      growth of autografts. The younger the rabbit the more growth is aided. This
      beneficial effect decreases gradually and becomes negligible after sexual
      maturity. Removal of the spleen is a powerful stimulus to the growth of
      transplants. The effect varies inversely with the age and usually is negligible
      after sexual maturity. The influence of age and splenectomy suggests that the
      spleen is most important in early life and after sexual maturity is either
      unimportant or its functions may readily be assumed by other tissues
      (hematopoietic). Anatomically the spleen is a highly complex structure, but
      biologically all the major elements of the spleen are simple as indicated by the
      uniform and marked regenerative capacity. There is a tendency for grafts to
      involute or atrophy with age, and grafts made in old rabbits without removal of
      the spleen may undergo complete atrophy. Grafts made in young rabbits,
      accompanied by splenectomy, have been observed for more than 3 years and may be
      said to be permanent. There is some evidence that subcutaneous autografts react
      to infections in the same way as the intact spleen.

PMID- 19868428
TI  - A GROUP OF PARATYPHOID BACILLI FROM ANIMALS CLOSELY RESEMBLING THOSE FOUND IN
      MAN.
AB  - 1. In addition to the paratyphoid bacilli already named there exists a group
      which occurs in a variety of animals and which culturally is the same as Bacillus
      schottmulleri. As a rule this group can be separated from the latter by the type
      of clumps formed when bouillon cultures are used as antigens, while other
      antigens and complement fixation tests have failed to differentiate it.
      Agglutination absorption tests sharply separate the animal from the human
      paratyphoids. 2. No differences have been detected between organisms of this
      group derived from a number of animals and a common name for them is desirable,
      but for the present it seems better to call them calf-, swine-, mouse-, etc.,
      typhus, according to the animal from which they were isolated. 3. Evidence exists
      in the literature that these organisms have been associated with food infections
      in man, particularly with what have been called paratyphoid B infections, but
      this function, as well as the part they play in animal diseases, is a subject for
      further study. 4. Well defined groups of paratyphoid such as Bacillus cholerae
      suis, the Voldagsen bacillus, Bacillus abortus equi, and Bacillus enteritidis are
      found in animals in addition to the organisms considered in this paper, and every
      attempt should be made to range newly isolated organisms in one or the other of
      these well recognized groups. 5. One of the objects in continuing this work was
      to find a method of differentiating these animal from the human paratyphoids less
      complicated than agglutination absorption. This object was not realized; the two
      groups are very similar and agglutination absorption seems to be the only means
      of classifying them.

PMID- 19868429
TI  - BACILLI OF THE HOG-CHOLERA GROUP (BACILLUS CHOLERAE SUIS) IN MAN.
AB  - 1. The organisms isolated by Hirschfeld from febrile cases resembling paratyphoid
      fever and named Paratyphoid C can be placed in the hog-cholera bacillus group by
      their agglutination absorption properties though they are not typical culturally.
      2. When fed to a pig a febrile disease resulted from which the animal recovered.
      After injection of hog-cholera virus the organisms fed were found generally,
      distributed and some of them had lost cultural characters so that they are
      brought into the class of typical hog-cholera bacilli except for their low
      virulence for rabbits. 3. While hog-cholera bacilli have many opportunities to
      infect man. they either are not able to grow in the human body or, what is less
      likely, they do grow and lose the characters that distinguish them.

PMID- 19868430
TI  - STUDIES ON CALCIUM AND MAGNESIUM METABOLISM IN DISEASE : I. CALCIUM AND MAGNESIUM
      METABOLISM IN LEPROSY.
AB  - In leprosy there is a definite retention of calcium. The more advanced the stage
      of the disease the greater is the degree of retention. This behavior on the part
      of leprous individuals may be taken as an indication that the organism is in need
      of calcium. Magnesium may also be retained in leprosy, but .the degree of
      retention is much less marked than in the case of calcium. With the exception of
      the retention of calcium and magnesium the leprous organism responds to changes
      in the intake of calcium and magnesium in the same manner as normal individuals.
      The results of this investigation suggest that in leprosy administration of
      calcium may be of benefit as an additional therapeutic measure in an endeavor to
      retard or arrest the progress of the bone changes characteristic of the disease.

PMID- 19868431
TI  - STUDIES ON CALCIUM AND MAGNESIUM METABOLISM IN DISEASE : II. CALCIUM AND
      MAGNESIUM METABOLISM IN MULTIPLE CARTILAGINOUS EXOSTOSIS.
AB  - In the stabilized stage of exostosis calcium exchange differs little from that of
      a normal individual whether the abnormal subject is maintained upon a calcium
      poor diet or upon one rich in this element. In the progressive stage of the
      disease calcium metabolism is markedly different from the normal in that calcium
      is lost from the body in large amounts when the subject is maintained upon a
      calcium-poor diet. This excessive elimination of calcium is by way of both the
      urine and feces in a normal ratio. When placed upon a calcium-rich diet calcium
      is retained to an extent not widely deviating from that obtained in normal
      subjects. A resumption to a calcium-poor diet again induces excessive calcium
      elimination. In the stabilized stage of exostosis magnesium excretion is two or
      three times greater than the intake whether the subject is maintained upon a diet
      poor or rich in magnesium. In the progressive stage of the disease the general
      type of magnesium excretion resembles that of the stabilized stage but the degree
      of elimination is not so marked. Magnesium added to the diet in the stabilized
      stage is promptly excreted. The same test applied to the progressive stage gives
      evidence of retention of some magnesium. The degree of retention, however, is
      much less than that shown by normal individuals. Absorption of both calcium and
      magnesium in exostosis is not inferior to that of normal subjects. The facts
      enumerated suggest that in the early stages of exostosis, that is during the
      proliferative cartilage changes, the progress of the disease may perhaps be
      checked by proper dietary procedure - restriction of calcium and magnesium
      intake.

PMID- 19868433
TI  - A METHOD FOR FIXING FILMS OF HUMAN BLOOD CELLS DURING THE AMEBOID MOVEMENT OF
      LEUCOCYTES AND THROMBOCYTES.
AB  - Feeding embryonated eggs of Heterakis papillosa to brooder chickens led to a
      disease of both ceca, characterized by the presence of a core consisting of fecal
      matter, coagulated blood, and emigrated cells from the mucosa. The walls of the
      ceca were thickened as a result of cell invasion and multiplication, invasion and
      multiplication of Amoeba meleagridis or allied parasites, and more rarely
      hemorrhage and edema. The respective parts played by Heterakis papillosa and the
      protozoa in starting the lesions and the source of the protozoa remain to be
      defined. The invasion of the liver by the protozoa was insignificant.

PMID- 19868432
TI  - A FURTHER EXPERIMENTAL STUDY ON EXCITATION OF INFECTIONS OF THE THROAT.
AB  - Improvements are described in the method of following temperature changes, and
      thus alterations in vasomotor tone, in exposed mucous membranes. Invention of an
      applicator holder, by means of which more sure and stable apposition of the
      thermopile terminals to the mucous surface may be effected has been the chief
      advance. Minor improvements have been the use of a saliva ejector and of better
      calibration technique. The palatine tonsils, like the palate, pharynx, and skin,
      react to chilling of the body surface with reflex vasoconstriction and ischemia.
      On rewarming the subject the tonsils quickly more than recover their former blood
      supply, actually becoming hyperemic; the skin returns to about its control
      condition; the pharynx and palate remain somewhat ischemic. The hypothesis is
      advanced that one factor in the beneficial hardening effect of cold bathing and
      outdoor living, with its incident heightened immunity to respiratory infection,
      may be the training of the vasomotor system in the direction of development in
      the pharynx of a reaction of hyperemia following chilling, similar to that
      observed in the tonsils of the present subjects. With inhalation of amyl nitrite,
      the skin temperature has always shown a sharp transient rise. The mucous
      membrane, if relatively ischemic, responds by a rise corresponding to the skin
      flush. If already hyperemic, local vasodilation in the mucous membrane with amyl
      nitrite is more than counterbalanced by the lowering of the general blood
      pressure, and the temperature falls. The flora of the pharynx and tonsils,
      studied by the unsatisfactory method described, showed, in several instances,
      after experimentation changes apparently due to proliferation of one of the
      microorganisms already present. In one case Streptococcus haemolyticus, in one
      Micrococcus catarrhalis, and in a third Bacillus influenzae was the organism
      showing a relative increase in numbers. The first two instances were associated
      with sore throat, the third with slight constitutional symptoms. The chilling in
      the experiments in no instance produced albuminuria or glycosuria, although a
      more dilute urine was apparently excreted during the experiments. A fall in
      hydrogen ion concentration, referable to the forced respiration, was noted.

PMID- 19868434
TI  - SEGMENTING TERTIAN MALARIAL PARASITES ON RED CORPUSCLES SHOWING LITTLE OR NO LOSS
      OF HEMOGLOBIN SUBSTANCE. EVIDENCE OF MIGRATION.
AB  - 1. Malarial parasites destroy more than one red corpuscle, migrating to another
      as soon as one is destroyed. 2. Pigmented segmenting parasites attached to red
      corpuscles whose hemoglobin is intact or nearly so are prima facie evidence of
      migration. 3. Infected corpuscles in tertian infections may be enlarged as a
      result of the large size of the attached parasite as well as by parasitic action.
      4. The young parasites resulting from the segmenting bodies attached to healthy
      red corpuscles usually attach themselves independently to the infected corpuscle
      and remain there until the corpuscle is destroyed.

PMID- 19868435
TI  - BLACKHEAD IN CHICKENS AND ITS EXPERIMENTAL PRODUCTION BY FEEDING EMBRYONATED EGGS
      OF HETERAKIS PAPILLOSA.
AB  - Feeding embryonated eggs of Heterakis papillosa to brooder chickens led to a
      disease of both ceca, characterized by the presence of a core consisting of fecal
      matter, coagulated blood, and emigrated cells from the mucosa. The walls of the
      ceca were thickened as a result of cell invasion and multiplication, invasion and
      multiplication of Amoeba meleagridis or allied parasites, and more rarely
      hemorrhage and edema. The respective parts played by Heterakis papillosa and the
      protozoa in starting the lesions and the source of the protozoa remain to be
      defined. The invasion of the liver by the protozoa was insignificant.

PMID- 19868436
TI  - EARLY CHANGES FOLLOWING THE INJECTION OF TUBERCLE BACILLI INTO THE METAPHYSIS OF
      THE LONG BONES OF ANIMALS.

PMID- 19868437
TI  - IMPORTANCE OF BLOOD GROUPS IN COMPLEMENT FIXATION REACTIONS.
AB  - 1. The presence of a natural anti-human hemolysin, only active against Group I
      and Group II cells, was demonstrated in over 50 guinea pigs, obtained from
      different sections of the surrounding country. It was shown that, in a majority
      of the sera tested, this hemolysin would be a contributing factor to an excess of
      amboceptor in the reaction, in the quantities of complement used in an antihuman
      complement fixation reaction. The hemolysin is specific, in as far as it can be
      absorbed with either Group I or Group Il cells, but cannot be absorbed with Group
      III or Group IV cells. 2. To determine the effect of the isohemolysins in human
      serum, twenty sera were tested against cell suspensions of the four human groups.
      Tests were also run with twenty-six human sera against all four group cell
      suspensions, with complement that had the natural anti-human hemolysin absorbed
      from it. In both experiments various degrees of hemolysis were obtained with all
      but two sera against cell suspensions from Groups I, II, and III, but no
      hemolysis was obtained with any serum against a Group IV cell suspension. 3. The
      importance of the human isohemolysins and the natural anti-human hemolysm in
      complement was demonstrated by performing complement fixation tests upon twenty
      six human sera, cell suspensions of all four human groups for each serum tested
      being used. A marked variation in the reaction occurred with a large percentage
      of the sera tested. This variation in a single serum might be as great as a
      negative reading with Group I cells to a double plus reading with Group IV cells.
      4. That the isohemolysins, alone, in human serum are of importance in the
      reaction was shown by running complement fixation tests upon seventeen human sera
      with the four group cell suspensions and complement from which the natural anti
      human hemolysin had been absorbed. Results showed a much weaker reaction, in a
      large number of the sera, with Group I, Group II, and Group III cells than with
      Group IV cells. 5. Experiments to determine a relation between the human blood
      groups and natural anti-sheep hemolysin present in human serum gave negative
      results. It was shown, however, with twenty-six human sera tested against twenty
      three different sheep cell suspensions that there is a wide variation in the
      activity of the natural anti-sheep amboceptor present in any human serum when it
      is tested against different sheep cell suspensions. A human serum capable of
      completely hemolyzing the cells of one sheep may fail to give any hemolysis
      whatever when tested against another sheep cell suspension. 6. Tests were made
      for natural anti-sheep hemolysin in guinea pig serum. The serum from sixteen
      different guinea pigs was tested against a total of twenty-one sheep cell
      suspensions. A natural anti-sheep hemolysin was present in all the guinea pigs
      tested against one of the sheep cell suspensions. The same guinea pigs tested
      against the other sheep cell suspensions failed to show any hemolysis.

PMID- 19868438
TI  - EXPERIMENTS ON THE PRODUCTION OF SPECIFIC ANTISERA FOR INFECTIONS OF UNKNOWN
      CAUSE : III. NEPHROTOXINS: THEIR SPECIFICITY AS DEMONSTRATED BY THE METHOD OF
      SELECTIVE ABSORPTION.
AB  - As Pearce has shown, a serum highly injurious to the kidney of dogs can be
      produced by the immunization of rabbits with washed renal tissue of the dog. The
      histological findings are striking and characteristic, the most noteworthy being
      a glomerular lesion of special type. The renal changes differ much from those
      Pearce described. The injury to the kidney is not to be explained by hemolytic
      and hemagglutinative elements in the serum. The complete removal of such
      antibodies by exhaustion of the serum with successive portions of red cells fails
      to lessen materially its ability to cause kidney lesions. Furthermore, an
      ordinary hemolytic and hemagglutinative serum produced by the use of washed red
      cells as antigen fails to cause similar lesions. The distinctive, injurious
      principle of antikidney serum can be removed and the latter rendered innocuous by
      absorption with kidney tissue. To all practical intents and purposes it would
      seem that nephrotoxic serum of. the sort here described is specific. If infected
      tissue is to be utilized as an antigen for the production of therapeutic antisera
      the latter must in some instances be exhausted with tissue of the same sort prior
      to introduction into the animal body.

PMID- 19868439
TI  - EFFECT OF INTRABRONCHIAL INSUFFLATION OF ACID.
AB  - Acid administered to rabbits by intrabronchial insufflation causes an immediate
      and extreme damage of the lung tissue. Within certain limits the degree and
      extent of the injury vary according to the concentration of the acid. With the
      greater concentrations death occurs promptly, almost immediately, and the lethal
      process has associated with it a decreased permeability of the pulmonary vessels.
      The latter fact has been confirmed by postmortem arterial injections. With weaker
      solutions the results, grossly and histologically, resemble those noted after
      influenzal pneumonia and gas poisoning. Thus, there is destruction of the
      epithelium of the bronchioles, the alveolar ducts, and the alveoli. The extent of
      the damage to the alveolar walls varies. Exudation occurs into the alveolar,
      interstitial, perivascular, and peribronchial tissues. Primarily this exudate is
      serous, but a rapid deposition of fibrin occurs, and later polymorphonuclear
      leucocytes and erythrocytes accumulate. In different animals, or in different
      portions of the same lung, there may be consolidations of different types,
      serofibrinous, hemorrhagic, or purulent, with or without destruction of the
      alveolar walls. Subsequent changes relate to the organization of the exudate,
      necrosis, proliferation of the epithelium in the alveoli and bronchi, and,
      finally, to the regeneration of the pulmonary parenchyma. Experiments now in
      progress indicate that similar changes can be induced by various acids, both
      inorganic and organic. Experiments also show that similar changes are produced in
      other species of animals but that species differ in their resistance according to
      the acid and the concentration in which it is employed.

PMID- 19868440
TI  - EPITHELIAL PROLIFERATION FOLLOWING THE INTRABRONCHIAL INSUFFLATION OF ACID.
AB  - The damage caused by the introduction of acid into the pulmonary parenchyma is
      repaired rapidly. The depth of the necrosis determines which elements will
      participate in the repair. If epithelium alone is injured, epithelium alone takes
      part in the repair. When the damage involves the deeper tissue, organization by
      granulation competes with and impedes the development of the epithelium. An
      overproduction of the epithelium occurs and may form bronchiolar polypi or extend
      into the peribronchial tissue.

PMID- 19868441
TI  - PRODUCTION OF PULMONARY INFARCTS BY THE INSUFFLATION OF ACID.
AB  - Intrabronchial insufflation of acid causes immediate necrosis of the walls of
      many alveoli. Thrombosis of the alveolar vessels is an associated phenomenon.
      When a large number of vessels becomes affected, a clot propagates rapidly into
      the larger supplying vessels. The resulting lesion is indistinguishable from a
      hemorrhagic infarct. The infarct-like areas so frequently encountered in
      influenzal pneumonia, it is not unlikely, have their origin in a similar process.
      Infarction depends not only upon thrombosis or embolism of the large vessels, but
      may be initiated by extensive damage to the capillary bed. By this process
      infarcts may form in organs which are normally protected by collateral
      circulation.

PMID- 19868442
TI  - A STUDY OF BACILLUS PYOGENES.
AB  - Bacillus pyogenes is probably quite common in this country, as it is known to be
      in Europe. A careful study of twelve strains from cattle and one from a hog has
      disclosed the following characteristics which have not been reported or have been
      in dispute. Bacillus pyogenes is Gram-positive and pleomorphic, producing forms
      ranging from short chains of streptococcoid elements to branching filaments. It
      is hemolytic, producing the beta type of hemolysis in blood agar. It is not
      hemoglobinophilic, though its growth is greatly favored by some higher protein
      material such as egg albumin, serum, or blood. It ferments xylose in addition to
      the substances previously reported. The coagulation of milk by Bacillus pyogenes
      is primarily an enzyme coagulation and the subsequent digestion of the curd takes
      place in an acid medium. The intravenous injection of rabbits was invariably
      fatal. The lesions most commonly developed were those of the bones. Paralysis was
      frequently produced, and in each case was caused by lesions in the vertebrae
      exerting pressure against the ventral columns of the spinal cord. Muscle
      abscesses were also frequently produced. The authors regard the organism as
      belonging to the Corynebacteria rather than to the influenza group.

PMID- 19868443
TI  - THE BILIARY FACTOR IN LIVER LESIONS.
AB  - There are excellent reasons for employing the rabbit in an experimental analysis
      of the biliary factor in liver lesions; and it is possible to obtain in this
      animal results uncomplicated by infection or by intercurrent cirrhosis. Ligation
      of the common duct of the rabbit results in a mixed lesion from injury throughout
      the entire length of the bile channels. By obstructing single ducts and altering
      the portal stream we have produced cirrhoses of pure monolobular and diffusely
      intralobular types. The character of the connective tissue changes is determined
      by the path of escape of bile from the collecting system, which in turn is
      largely conditional upon the secretory activity, while this again is dependent
      upon blood flow. The portal flow is largely diverted from regions of local stasis
      through encroachment on the stream bed by the dilated ducts. There is a large
      margin of safety in bile elimination by the normal hepatic tissue. Less than a
      quarter of the liver of the rabbit, and this deprived of its entire portal
      stream, will suffice to keep the organism free from clinical jaundice and healthy
      when the remainder of the liver, which receives all of the portal blood, has its
      ducts ligated. The vicarious elimination thus illustrated is of great importance
      for regions of local stasis by keeping the blood relatively free from bile, thus
      preventing resecretion into such regions and facilitating exchange from them into
      the body fluids. Our experimental monolobular and intralobular cirrhoses are the
      result of the limitation of biliary lesions to special levels of the duct system.
      Their resemblance to the different forms of "biliary" cirrhosis associated with
      Hanot's name is close, and the diverse liver lesions of Hanot's disease are
      readily explained on the assumption that the stasis, with or without infection,
      which is indubitably here present, has its situation at different levels in
      different cases. There are reasons for the view that bile stasis per se may
      sometimes be a prime cause of the malady. Certainly such stasis must be thought
      of as acting to complicate many chronic liver lesions. In a later paper
      experiments on the dog will be described essentially similar in result to those
      on the rabbit as here set forth.

PMID- 19868444
TI  - INFLUENCE OF VARIATIONS OF MEDIA ON ACID PRODUCTION BY STREPTOCOCCI.
AB  - The results of variations in acid production in 1 per cent dextrose fermented and
      unfermented veal broth modified by the addition of 4 per cent of horse serum or 2
      per cent of peptone have been recorded. Human streptococci and a group of low
      acid-producing streptococci from milk produce less acid in the simpler broths
      (fermented and unfermented). 2 per cent peptone fails to increase the amount of
      acid produced by these two groups. The bovine streptococci act much the same as
      those of human origin. The equine streptococci apparently do not require serum in
      addition to carbohydrate since they tend to produce less acid in serum media. The
      following figures indicate the average minimum and maximum acid production of the
      various streptococci under the conditions set forth in the experiment. Human: pH
      4.97 to 5.66; titratable acidity 4.51 to 3.66 Bovine: pH 4.56 to 4.77; titratable
      acidity 7.0 to 5.74 Equine: pH 4.86 to 5.42; titratable acidity 5.38 to 4.24 Low
      acid-producing streptococci from milk: pH 6.28 to 5.14; titratable acidity 2.56
      to 4.28.

PMID- 19868445
TI  - ENHANCEMENT OF THE OPSONIZING AND AGGLUTINATING POWERS OF ANTIPNEUMOCOCCUS SERUM
      BY SPECIFIC PRECIPITATING SERUM.
AB  - 1. No demonstrable antiopsonins are formed in rabbits following the intravenous
      injection of monovalent pneumococcus horse sera, Types I, II, and III. 2. The
      serum of rabbits injected with immune pneumococcus horse serum, Type I, II, or
      III, or with normal horse serum, when mixed in the proportion of 1:4 with Type I
      or Type II pneumococcus horse serum, can greatly augment, in vitro, the
      opsonization and agglutination of Type I and Type II pneumococci by the
      homologous immune horse sera. No similar effect is obtained with Type III serum
      and pneumococci. 3. The increase in opsonization and agglutination is dependent
      upon (a) specific sensitization of the pneumococci by the homologous immune serum
      and (b) the presence of the precipitating serum. In the absence of sensitization,
      as when a heterologous or normal horse serum is employed, opsonization and
      agglutination do not occur, even though a precipitating mixture is provided. The
      substitution of normal rabbit serum for the precipitating rabbit serum gives
      opsonization and agglutination in dilutions slightly higher than are effected
      with salt solution only, due possibly to the more favorable medium created for
      the leucocytes by the addition of 25 per cent of whole rabbit serum. 4. Different
      methods of combining the immune horse serum, precipitating rabbit serum, and
      pneumococci yield very similar results, preliminary sensitization of the bacteria
      before precipitation, or precipitation in the rabbit-horse serum mixture before
      the addition of the pneumococci for sensitization causing little if any
      difference in result from that obtained when immune horse serum, precipitating
      rabbit serum, and pneumococci are all mixed and incubated together. 5. This
      increased opsonization in the test-tube does not seem to be paralleled by
      increased protective power, or at any rate such protection is not readily
      demonstrated.

PMID- 19868446
TI  - USE OF THE SINGLE CELL METHOD IN OBTAINING PURE CULTURES OF ANAEROBES.
AB  - The pipette method has proved a feasible method of obtaining one-cell pure
      cultures of anaerobes. Both bacilli and spores may be used as seeding material,
      but spores give a much higher percentage of positives. Boiling alone affords a
      sufficient degree of anaerobiosis to the medium for initiating one-cell growths,
      and semisolid agar is the most convenient form of medium. Exposure to air during
      isolation apparently has no effect on the viability of spores of anaerobes, but
      young bacilli of some species suffer from a comparatively short exposure to free
      oxygen.

PMID- 19868447
TI  - EXPERIMENTAL INOCULATION OF MALARIA BY MEANS OF ANOPHELES LUDLOWI.
AB  - Three persons were experimentally inoculated with malaria by means of Anopheles
      ludlowi reared from larvae and infected with a pure strain of subtertian
      plasmodium (Plasmodium falciparum), thus proving that there exists no mechanical
      impediment or obstacle to the free exit of sporozoites from the salivary ducts or
      proboscis. In the dissection of infected mosquitoes there were no evidences of
      degenerated zygotes. Sporozoites appeared promptly in the salivary glands (9 to
      12 days). Inoculation occurred with ease either in an interrupted feeding or
      after mosquitoes had been fed twice previously. The period of incubation was 14
      and 18 days. The clinical manifestations were more severe in the subject that had
      never been infected with malaria previously, while the splenic enlargement was
      most pronounced in the subject infected after a long interval of freedom from
      malaria. In a third subject already suffering from tertian malaria there was only
      the slightest evidence of physical illness elicited by the superimposed
      subtertian infection; his temperature, however, became duly elevated. The type of
      febrile reaction in the two uncomplicated cases was at first tertian, becoming
      quotidian later, and this phenomenon in a pure strain leads strongly to the
      supposition that Plasmodium falciparum possesses inherently both tertian (or
      subtertian) and quotidian tendencies, as well as its well known tendencies to
      cause fever of the irregularly remittent or continued type. The creation of a
      specific plasmodium to account for clinical forms of aestivo-autumnal or
      subtertian malaria having a quotidian periodidty is probably unwarranted. In
      consideration of the facility with which this species can be infected and man
      inoculated experimentally, the occurrence of naturally infected wild specimens,
      and the positive epidemiological evidence, there should no longer exist in the
      minds of sanitarians any doubt as to its being a malarial carrier. Operations
      against this species can therefore be recommended without reservation and should
      be carried out without delay.

PMID- 19868448
TI  - STUDIES ON BACILLUS MURISEPTICUS, OR THE ROTLAUF BACILLUS, ISOLATED FROM SWINE IN
      THE UNITED STATES.
AB  - In the United States organisms, which culturally are mouse septicemia or swine
      erysipelas bacilli, have been isolated from the tonsils of five of sixteen pigs
      examined. These pigs all had hog-cholera, but it is probable that the bacilli
      were in the tonsils before they were infected with hog-cholera, and there is no
      evidence that they played any part in the disease. The distribution of the
      infection seemed to be restricted as most of the pigs from which the bacilli were
      obtained came from one litter. As we do not have clinical rotlauf, or swine
      erysipelas, in this country, as these organisms, in Europe, have been found in a
      large percentage of apparently normal swine, and as the disease is produced with
      difficulty by the injection of cultures, the question may be raised whether they
      are not secondary invaders rather than the primary cause of the disease with
      which they have been associated, or else whether the resistance of swine on the
      European continent does not differ from that of our breeds as a result of
      differences in foods. It is possible that the mouse septicemia bacilli found in
      this country may differ culturally from those present in animals with swine
      erysipelas. With this in mind, the carbohydrate reactions, as well as other
      cultural characters not necessary for the identification of the bacilli isolated,
      have been studied. The disease produced by the injection of these bacilli into
      mice and pigeons has been studied and shown to be largely an intracellular
      process. The organisms are taken up by the endothelial cells lining the veins and
      capillaries; there they multiply and soon kill the cells. It has also been shown
      that the only type of cell in the blood stream which contains bacteria is the
      endothelial leucocyte, and the probabilities are that the free phagocytes have
      been detached from the lining of the vessels. The disease is acute, and the
      indications are that in the cells the bacilli find a favorable medium for their
      growth. While phagocytosis may in general be an immune reaction, in this case it
      appears to favor the parasite rather than the host.

PMID- 19868449
TI  - EFFECTS OF ENZYMES IN SERUM ON CARBOHYDRATES AND THEIR RELATION TO
      BACTERIOLOGICAL TECHNIQUE.
AB  - It has been shown that enzymes in serum will change maltose, dextrin, and starch
      so that they will react as dextrose in media. These enzymes are destroyed by
      heating to 60 degrees C. for 15 minutes, but they are present in sera that have
      been refrigerated for as long as 18 months. The practice of using carbohydrate
      media containing unheated serum should be discouraged, and if it is used the
      possibility that the carbohydrate may be changed by the enzymes present must be
      considered.

PMID- 19868450
TI  - A MODIFICATION OF VAN LEERSUM'S BLOODLESS METHOD FOR RECORDING BLOOD PRESSURES IN
      ANIMALS.
AB  - It has been shown that enzymes in serum will change maltose, dextrin, and starch
      so that they will react as dextrose in media. These enzymes are destroyed by
      heating to 60 degrees C. for 15 minutes, but they are present in sera that have
      been refrigerated for as long as 18 months. The practice of using carbohydrate
      media containing unheated serum should be discouraged, and if it is used the
      possibility that the carbohydrate may be changed by the enzymes present must be
      considered.

PMID- 19868451
TI  - REPRODUCTION IN VITRO OF ENTAMOEBA TETRAGENA AND ENTAMOEBA COLI FROM THEIR CYSTS.
AB  - 1. The vegetative forms of amebae may be developed in vitro from the cysts. 2.
      The cysts of Entamoeba tetragena and Entamoeba coli each produce only a single
      vegetative individual. It has not been observed in vitro that a number of
      daughter amebae, corresponding to the number of nuclei present in the cyst,
      emerge from the mother cyst, as claimed by Casagrandi and Barbagallo, Schaudinn,
      and a number of other investigators. 3. The daughter nuclei in the cystic stage
      correspond to the gamete nuclei of other protozoa. The syngamic nuclear union in
      the case of these two amebae does not take place in the tetranuclear stage of the
      cyst, as claimed by Schaudinn and Wenyon, but during reproduction. 4. The process
      of autogamy of both amebae is not restricted to two nuclei; it may involve more
      than two, which unite to form a syncaryon. In the case of all other protozoa,
      autogamy is restricted to two nuclei. 5. In order to distinguish the two types of
      autogamy, one has been termed simple autogamy and the other polynuclear autogamy.
      The latter may again be classified according to the number of nuclei involved, as
      trinuclear and tetranuclear autogamy. 6. The majority of cysts treated for 5
      minutes in a 2 per cent solution of hydrochloric acid survives. 7. It was
      possible to demonstrate in vitro the developmental cycle of Entamoeba tetragena.
      8. No evidence of heterogamy has been observed in vitro in Entamoeba tetragena or
      Entamoeba coli. 9. The vegetative form of Entamoeba tetragena, at a certain stage
      of its life cycle in vitro, shortly after its formation, has not only one or two,
      but may have as many as three or four nuclei.

PMID- 19868452
TI  - ETIOLOGY OF YELLOW FEVER : XII. CHEMOTHERAPY VERSUS SEROTHERAPY IN EXPERIMENTAL
      INFECTION WITH LEPTOSPIRA ICTEROIDES.
AB  - In several series of experiments guinea pigs were variously infected with
      different amounts of Leptospira icteroides, either in the form of culture, organ
      emulsion from infected guinea pigs, or a mixture of both. The infecting materials
      were of different grades of virulence; in some series the amount given was near a
      single lethal dose, in others a subminimum lethal dose was given, i.e. causing
      mild infection with recovery in the majority of animals, and in still others the
      animals were injected with at least 50 minimum lethal doses of a mixture of a
      culture and a highly virulent organ emulsion from a guinea pig. The animals were
      inoculated intraperitoneally, and within about 30 minutes each was injected
      subcutaneously with a different amount of salvarsan or neosalvarsan. The amounts
      injected were in most series 0.0005, 0.001, 0.002, 0.005, 0.01, 0.02, and 0.03
      gm. per 350 to 450 gm. of body weight, and in one series, in addition to this
      dosage, 0.00005,0.0001, and 0.0002 gm. were also tried. Among the guinea pigs
      treated either with salvarsan or with neosalvarsan there were more recoveries
      than among the controls, but they were not in strict proportion to the amounts of
      the drugs injected. In the experiments with 50 minimum lethal doses of the
      infecting material there were several recoveries among those which received 0.001
      to 0.002 to 0.003 gm., but all passed through a typical infection with all its
      symptoms. It is extremely doubtful, therefore, whether salvarsan or neosalvarsan
      mitigated the severity of the infection. The fact is noteworthy that in the same
      series of experiments the guinea pigs receiving 0.00005 and 0.0001 gm., or
      thereabout, of salvarsan died 1 to 2 days sooner than the controls, which died in
      6 to 7 days. This suggests a possible earlier injury of the kidneys by the drugs,
      giving the leptospiras an easier and earlier access to, and localization in this
      organ. The inefficacy or dubious therapeutic value of salvarsan and neosalvarsan
      against the experimental icteroides infection of guinea pigs presents a close
      analogy to the observations already made by several investigators with Leptospira
      icterohaemorrhagiae. Several series of test-tube experiments were also made to
      determine the direct effect of salvarsan and neosalvarsan on Leptospira
      icteroides cultures. It was found, the injurious effect of alkalinity being
      eliminated, that the leptospiras remain motile for at least I hour in a
      concentration weaker than 1:10,000 of salvarsan or 1:1,000 of neosalvarsan. But
      they become gradually sluggish and succumb to the effect of the drugs at the end
      of 18 to 24 hours. The highest dilution which killed the leptospira in 18 hours
      was somewhere near 1:200,000. When added to a culture medium, salvarsan and
      neosalvarsan both suppressed the growth of icteroides when their concentration in
      the medium was 1:200,000. Hence these two drugs are highly poisonous for
      Leptospira icteroides. The serums derived from rabbits which received 0.05 gm. of
      salvarsan or neosalvarsan per kilo of body weight 1 hour before bleeding proved
      to be very different from a normal rabbit serum in their behavior toward
      Leptospira icteroides. In the salvarsanized or neosalvarsanized serums the
      leptospiras remained active for at least 1 hour but appeared somewhat sluggish at
      the end of 18 hours, and were all dead and degenerated when examined after 48
      hours. On the other hand, the leptospiras mixed with normal rabbit serum lived
      well and multiplied during the same period of time and under otherwise identical
      conditions (at 28 degrees C.) To these tubes another portion of culture was added
      to determine whether or not a rapidly detrimental toxic substance had appeared in
      the drugged serum while standing for 72 hours, but the organisms remained still
      active at the end of 1 hour, 24 hours being required to kill them. In another
      experiment the salvarsanized and neosalvarsanized serums, together with normal
      serum as a control, were first left standing for 72 hours, after which period a
      rich culture of icteroides was introduced. The organisms remained uninfluenced
      for 1 hour in all the serums, but at the end of 24 hours many of those in the
      drugged serums were dead, and none was left alive at the end of 48 hours. In
      normal serum they steadily increased in numbers and were all active. It is
      evident, then, that salvarsan or neosalvarsan introduced intravenously into the
      body of the rabbit is present in some form in the blood serum drawn at the end of
      1 hour. The substance present in such serum has a slowly operating injurious
      effect upon Leptospira icteroides. The action of the drugs seems to be slower
      after passage through the animal body than before. If this phenomenon were to
      take place also in the infected body injected with these drugs, it is obvious
      that in a rapidly evolving infectious disease like yellow fever the progress of
      the infection will be too rapid to allow the drugs to exert their beneficial
      effect upon the course of the disease. In direct contrast to the behavior of
      salvarsan and neosalvarsan in vivo and in vitro, anti-icteroides immune horse
      serum in a dose of 0.0001 cc., or 1 cc. of a 1:10,000 dilution, protected guinea
      pigs from an infection with at least 5,000 minimum lethal doses of icteroides
      when injected simultaneously, but the same serum failed to exert any injurious
      effect upon the organism when mixed in vitro in a concentration weaker than
      1:2,000. A rapid disintegration resulted with a concentration of 1:20 and almost
      complete agglutination and degeneration in 1:200. The contrast between
      chemotherapy, as carried out with salvarsan and neosalvarsan, and serotherapy
      demonstrated with an immune serum is apparently of considerable practical
      significance.

PMID- 19868453
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : VIII. EXPERIMENTAL STREPTOCOCCUS HAEMOLYTICUS
      PNEUMONIA IN MONKEYS.
AB  - 1. Pneumonia has been consistently produced in normal monkeys by intratracheal
      injection of Streptococcus haemolyticus. 2. The pneumonia produced has been shown
      to be comparable with hemolytic streptococcus pneumonia in man with respect to
      its clinical features, complications, and pathology. 3. Two pathologic types of
      the disease have occurred, interstitial pneumonia and confluent lobular
      pneumonia. Both types have been found in the same animal. 4. The type of
      pneumonia has appeared to be dependent upon the amount of streptococcus culture
      injected, interstitial pneumonia following the injection of small amounts and
      being an expression of considerable resistance, confluent lobular pneumonia
      following the injection of large amounts and being an expression of comparative
      lack of resistance. 5. Study of the distribution of streptococci in the lungs and
      of the character of the lesions in early stages of the disease has shown that
      streptococci may primarily invade the pulmonary tissue by penetration of the
      walls of the larger bronchial branches and that they are distributed from the
      points of invasion by way of the peribronchial, perivascular, and septal
      interstitial tissue and lymphatics. Infection of the alveoli is likewise
      primarily an interstitial invasion of the alveolar walls by streptococci. 6. In
      one experiment it was found that preliminary injury to the respiratory tract by
      gassing with chlorine and that lowering of resistance by a preceding
      intraperitoneal injection of Bacillus influenza without local injury to the
      respiratory tract greatly facilitated invasion of the lungs by Streptococcus
      haemolyticus. 7. A normal monkey inoculated in the nose and throat with
      Streptococcus haemolyticus failed to develop pneumonia and showed no evidence of
      infection of the upper respiratory tract.

PMID- 19868454
TI  - LOCAL AUTOINOCULATION OF THE SENSITIZED ORGANISM WITH FOREIGN PROTEIN AS A CAUSE
      OF ABNORMAL REACTIONS.
AB  - The skin irritant, xylol, when applied to the ears of sensitized and reinjected
      rabbits often causes a severe inflammation with the formation of crusts and
      destruction of tissue. Dry gangrene of the entire ear tip may result (Figs. 1, 2,
      and 3). The same agent, applied in the same dosage and in the same way, to the
      ears of (1) normal rabbits, (2) normal rabbits injected once with horse serum
      (serum controls), or (3) sensitized but not reinjected rabbits, causes only a
      mild inflammation with more or less edema. The inflammation and edema disappear
      in 2 or 3 days, leaving a practically normal ear. The ear lesions of the
      sensitized reinjected rabbits which develop after the application of xylol are
      interpreted as a primary anaphylactic reaction. This primary anaphylactic
      reaction is considered the result of a local autoinoculation of the ear tissues
      with circulating antigen. The local autoinoculation is brought about by the
      irritant action of the xylol which causes an inflammation and edema of the site
      of application. An anaphylactic reaction may now occur because the inflamed
      tissues are more active metabolically than normal tissues and therefore the
      inflamed cells are affected by more antigen per unit of time than the normal
      cells. A subliminal concentration of antigen for non-inflamed, sensitized cells
      may thus become effective when inflamed sensitized cells are concerned. This
      process may theoretically occur in any tissue of a sensitized animal which can
      show an anaphylactic reaction, for example the intestines, lungs, heart, skin,
      nerves, arteries, etc. It is possible that this interplay of conditions may
      explain a number of functional abnormalities in the human subject.

PMID- 19868455
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : IV. CUTANEOUS SYPHILIS. PART 1. AFFECTIONS
      OF THE SKIN AND APPENDAGES.
AB  - From the study of a large series of rabbits with outspoken manifestations of
      generalized syphilis, lesions of the skin and appendages were found to constitute
      one of the largest and most varied groups of such affections. The conditions
      noted consisted of alopecias, onychia and paronychia, and lesions of the skin
      proper. It was found to be a matter of some difficulty to make a positive
      diagnosis of syphilitic alopecia, but there were three and possibly four
      conditions which appeared to be attributable to such an infection. The first of
      these took the form of a general or local roughening of the coat with falling of
      the hair which produced the typical moth-eaten appearance associated with
      syphilitic alopecia in the human subject. A second form of alopecia was
      essentially an abnormal looseness of the hair which permitted large areas of the
      body to be completely denuded. The third type of alopecia was associated with
      definite skin changes, and the hair was readily removable together with an
      adherent mass of epithelial scales. Paronychia was comparatively rare but was
      readily recognized by a characteristic infiltration and exfoliation of the skin
      about the base of the nails. The incidence of onychia is uncertain. Late in the
      course of the investigation it was found that alterations in the nails which were
      not entirely characteristic in themselves might occur in consequence of a
      syphilitic involvement of the nail beds which could not be detected by ordinary
      methods of examination. The cases which were recognized as syphilitic were those
      which showed an associated paronychia. Lesions of the skin were found to be one
      of the most frequent manifestations of a generalized infection in the rabbit.
      These lesions were divided into three classes: first, granulomatous lesions,
      second, infiltrations, and third, erythemata. The granulomata were lesions of a
      fleshy character which tended to grow to a very large size and presented all the
      characteristics of circumscribed primary lesions of the scrotum. The conditions
      described as cutaneous infiltrations included two general types of lesions, one a
      flattened and rather diffuse process, the other an elevated and sharply
      circumscribed papule. As a class, these lesions were very prone to secondary
      alterations and in this way gave rise to a great variety of conditions which in
      general resembled the diffuse primary lesions of the scrotum and the papular
      lesions resulting from local dissemination. A third type of lesion resembling the
      macular erythemata of man was observed in a small number of animals, and while no
      definite proof of the specific origin of these lesions was obtained, the evidence
      available was strongly suggestive. In addition, several other cutaneous
      affections were noted which have not as yet been thoroughly investigated. It is
      suggested, however, that these processes may bear some relation to infection with
      Treponema pallidum.

PMID- 19868456
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : IV. CUTANEOUS SYPHILIS. PART 2. CLINICAL
      ASPECTS OF CUTANEOUS SYPHILIS.
AB  - From the study of a large number of rabbits with generalized cutaneous syphilis
      following local inoculation with Treponema pallidum, lesions were found most
      often about the hind feet and legs, the head, the front feet and legs, and the
      tail. There was further evidence of a selective distribution of cutaneous lesions
      in the fact that, on a given part of the body, the lesions were usually confined
      to a few restricted areas. About the head, they occurred almost exclusively on
      the sides and bridge of the nose, the lids, the brows, the lips, and the base and
      free portions of the ears. On the front feet and legs, the seat of predilection
      was the extensor and lateral surfaces of the fore arm, the carpus, and the feet,
      while on the posterior extremities they were situated upon the dorsum and lateral
      surfaces of the feet and ankles from the level of the tendo achillis to the base
      of the fifth toe. The positions of greatest frequency were the region of the
      tarsus and external malleolus, the base of the fifth metatarsal, the lateral and
      posterior surfaces of the heel and tendo achillis, and the base of the fifth toe.
      In many instances, the positions of predilection were exposed positions or areas
      of skin covering bony or tendinous prominences. It was also found that the
      character of the lesions differed somewhat in the various locations. The lesions
      of the head were mostly small circumscribed papules or processes of diffuse
      infiltration; on the fore arms and feet, affections of this type were about
      equally divided with larger granulomatous masses of a chancre-like character,
      while on the hind feet and legs, granulomatous lesions were far more numerous
      than those of any other type and frequently reached a very large size. The
      cutaneous eruption usually consisted of only a few lesions confined to some one
      part of the body, but occasionally they were more numerous and more widely
      distributed. In this connection, it was noted that when multiple lesions appeared
      in a given area at about the same time, the growth of most of them was abortive,
      and, as a rule, only one or two developed to any considerable size. Especial
      emphasis was placed upon this phenomenon of inhibition as a factor of fundamental
      importance in the experimental infection. From clinical observation, it was found
      that, as a rule, the first cutaneous eruption occurred at from 2 to 4 months
      after inoculation but might occur either earlier or later, depending upon the
      circumstances in the individual case. The earliest eruptions appeared 3 weeks
      after inoculation and the latest 2 years and 8 months, but, as a rule, the time
      between inoculation and the appearance of the first eruption did not exceed 4 to
      6 months. Successive crops of cutaneous lesions appeared in a number of animals
      usually within the first 6 months after inoculation. In a few instances, however,
      there were repeated eruptions extending over a period of 2 years or more, the
      longest recorded period being 3 years and 7 months. The duration of individual
      lesions was found to be extremely variable, ranging from a few days in the case
      of a macular erythema to more than 2 years in the case of a few granulomatous
      lesions. The average duration of the lesions appeared to vary somewhat with the
      nature of the lesion but on the whole was not more than 2 to 4 months. No limits
      could be fixed, however, for the duration of an active skin infection as a whole.
      Again, it was found that the cutaneous infection tended to pursue a periodic or
      relapsing course. This was seen in the mode of growth and resolution of
      individual lesions, the occurrence of successive periods of eruption, and the
      recurrence of completely healed lesions, all of which was interpreted as evidence
      of the essential relapsing nature of syphilitic infections.

PMID- 19868457
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : V. SYPHILITIC AFFECTIONS OF THE MUCOUS
      MEMBRANES AND MUCOCUTANEOUS BORDERS.
AB  - In a series of more than 200 rabbits in which generalized lesions were observed
      following local inoculation with Treponema pallidum, there were a number of
      animals in which characteristic lesions were noted upon mucous membranes or along
      mucocutaneous borders. These lesions were distributed with about equal frequency
      between the nose or nasolacrimal system and the eyelids on the one hand, and the
      genital and anal regions on the other. The lips and buccal mucosa appeared to be
      less subject to localized infections unless the papillomatous growths noted on
      the lips and under side of the tongue should prove to be in some way connected
      with such an infection. In many instances, the local reaction was initiated by an
      acute inflammatory process, and in the case of nasal and genital infections, a
      definite exudate was formed. The succeeding stages of the reaction consisted in
      an infiltration of the parts involved, together with a variable degree of
      proliferation of fixed tissue cells, leading eventually to necrosis and
      ulceration. The resulting lesions differed according to their location and the
      character of the reaction in the individual case. Localized infections of the
      nose occurred in several forms, first, as a rather diffuse affection of the nasal
      mucosa characterized by the presence of a mucopurulent exudate, second, as a more
      or less circumscribed process of infiltration with an especial predilection for
      the region of the anterior nares, and third, as a granulomatous process involving
      the alae in particular. Involvement of the nasal mucosa was very commonly
      associated with lacrimal overflow and with some degree of conjunctivitis. The
      lesions of the eyelids were usually small, elevated papules or lesions of an
      ulcerative character some of which were surrounded by a zone of infiltration. In
      exceptional instances, large granulomatous lesions occurred along the margins of
      the lower lids. Infection of the penis and sheath gave rise to conditions
      analogous to those of the nose. In one group of animals, there was a diffuse
      affection characterized by redness and swelling of the parts with a mucopurulent
      exudate, in another there were circumscribed or diffuse infiltrations, while in a
      third the lesions formed were indurated granulomatous masses. Secondary necrosis
      with erosion or ulceration was a common feature of all these conditions.
      Localized infections in the region of the anus differed from those in other
      localities chiefly in the absence of an exudative group of affections and in the
      frequency with which lesions of a papillomatous type occurred. Lesions of mucous
      membranes and mucocutaneous borders developed at periods of time varying from a
      few weeks to several months after inoculation. Most of them were rather enduring
      and in several instances persisted in an active condition for considerably more
      than a year.

PMID- 19868458
TI  - STUDIES ON ENDOTHELIAL REACTIONS : II. THE ENDOTHELIAL CELL IN EXPERIMENTAL
      TUBERCULOSIS.
AB  - 1. The epithelioid cell is of definitely endothelial origin. 2. The only reliable
      means of identifying and tracing this cell is, at the present time, a colloidal
      suspension of carbon, injected intravenously. Benzidine dyes will not accomplish
      this if used alone. 3. There is little evidence that the local tissue elements
      take an active part in the process of tubercle formation, until after the lesion
      is formed; the reaction is, in a sense, exudative, since the lesion is produced
      from cells which migrate to the site of inflammation. 4. The lymphocyte appears
      late and is not to be considered as a potential epithelioid cell; its presence in
      the tubercles is as yet unexplained.

PMID- 19868459
TI  - STUDIES ON ENDOTHELIAL REACTIONS : III. THE ENDOTHELIUM IN EXPERIMENTAL PULMONARY
      TUBERCULOSIS.
AB  - 1. The injection of a colloidal suspension, or sol, of carbon into the veins of a
      living animal, as recommended by McJunkin, furnishes an apparently reliable means
      of tracing the so called epithelioid cell of the pulmonary tubercle from its
      origin in the vascular endothelium to the lesion. 2. Experimental tubercles are
      formed in the lung, as in the liver, primarily by cells originating in the
      capillary endothelium. These cells are probably present in small numbers in the
      normal lung, lying free both in the alveolar wall and the air vesicles. In
      response to infection they proliferate in the capillary walls in the vicinity of
      the invading organisms, migrate in steadily increasing numbers, and, arriving at
      the site of the infection, further multiply and to some extent fuse to form the
      syncytia known as giant cells. 3. The epithelial cell takes no active part in the
      process; its proliferation tends to repair denuded surfaces and is regenerative
      rather than combative or phagocytic in nature. This cell is free from carbon and
      stains only diffusely with carmine, in contradistinction to the endothelial cell
      which readily takes up both pigments in granular form. 4. The cells of
      endothelial origin not only phagocytose tubercle bacilli, but carry them into the
      tissues, for example into lymph nodes, by way of the lymphatics, or into other
      lung lobules by way of the air passages, in which they are readily demonstrable.

PMID- 19868460
TI  - STUDIES ON THE ENZYMES OF PNEUMOCOCCUS : I. PROTEOLYTIC ENZYMES.
AB  - 1. Pneumococci contain an intracellular enzyme or enzymes which (a) hydrolyze to
      some extent intact protein and (b) hydrolyze with striking avidity peptones. The
      optimum reaction for hydrolysis is pH 7 to 7.8, which also represents the optimum
      for the growth of pneumococcus. For convenience the terms "protease" and
      "peptonase" have been used, but no assumption is made as to whether the two
      actions, proteolysis and peptolysis, are due to two separate enzymes or are two
      activities of the same enzyme. 2. Solutions of intracellular substance of
      comparable enzymic activity may be prepared by dissolving the bacteria in bile,
      in sodium choleate, or by mechanical and autolytic disintegration of the cell. 3.
      The rapidity with which peptone is hydrolyzed is proportional to the
      concentration of the enzyme. 4. Heating the enzyme for 10 minutes at 100 degrees
      C. destroys its activity. 5. Increasing the acidity to pH 5, the acid death-point
      of pneumococcus, suspends activity but does not destroy the enzyme, for activity
      is restored by readjustment to pH 7.8. 6. Attenuation of virulence to 1/1,000,000
      of the original virulence had no measurable quantitative effect on the enzyme
      activity.

PMID- 19868461
TI  - STUDIES ON THE ENZYMES OF PNEUMOCOCCUS : II. LIPOLYTIC ENZYMES: ESTERASE.
AB  - 1. Pneumococci contain an intracellular enzyme of marked lipolytic activity as
      measured by the acid liberated by its action on tributyrin. 2. Enzyme-containing
      solutions may be prepared by dissolving pneumococci in bile, or by extraction by
      other means. 3. The optimum reaction for maximum activity of the endolipase is
      about pH 7.8, which coincides with the optimum hydrogen ion concentration for
      growth of pneumococci. 4. Heating the enzyme for 10 minutes at 70 degrees C.
      destroys its activity. 5. Attenuation of virulence of pneumococcus had no
      measureable effect on enzyme activity. 6. The possible relation of the endolipase
      to the mechanism of bile solubility is discussed.

PMID- 19868462
TI  - STUDIES ON THE ENZYMES OF PNEUMOCOCCUS : III. CARBOHYDRATE-SPLITTING ENZYMES:
      INVERTASE, AMYLASE, AND INULASE.
AB  - 1. A method is described for the preparation of an active enzyme-containing
      solution of pneumococci, in which no living cells are present. These enzymes are
      capable of hydrolyzing sucrose, starch, and inulin. 2. The invertase and amylase
      of pneumococcus are active within the limits pH 5 to 8, with an optimum reaction
      of about pH 7. This reaction range corresponds closely with limiting hydrogen ion
      concentrations which define growth of the organism in the presence of
      carbohydrate. 3. These studies indicate that the enzymes described are not true
      secretory products of the living cell, but are of the nature of endoenzymes,
      since their activity can be demonstrated only when cell disintegration has
      occurred.

PMID- 19868463
TI  - EPINEPHRINE CONTENT OF THE SUPRARENAL GLANDS IN ANAPHYLAXIS.
AB  - The epinephrine store of the suprarenal glands remains unaltered in guinea pigs
      and rabbits which have been sensitized to ox serum, or subjected to varying
      degrees of anaphylactic shock by the reinjection of the foreign protein.

PMID- 19868464
TI  - EXPERIMENTAL STUDIES ON YELLOW FEVER OCCURRING IN MERIDA, YUCATAN.
AB  - Injections into guinea pigs of the blood and the emulsions of liver and kidney
      obtained at autopsy from a fatal case of yellow fever in Merida induced in some
      of these animals, after a period of several days incubation, a rise of
      temperature which lasted 1, 2, or more days. When killed for examination at this
      febrile stage the animals invariably showed hemorrhagic areas of various size,
      sometimes few and sometimes numerous, in the lungs, and also, though less
      constantly, in the gastrointestinal mucosa, together with general hyperemia of
      the liver and kidneys. In a guinea pig (No. 6) inoculated with the liver emulsion
      of Case 1 there was a trace of jaundice on the 9th day. Injections of the blood
      or liver and kidney emulsions from such animals into normal guinea pigs
      reproduced the febrile reactions and the visceral lesions. The majority of the
      animals which were allowed to live and complete the course of the infection
      rapidly returned to normal (within several days). Examinations of these surviving
      guinea pigs after 2 weeks revealed the presence of rather old hemorrhagic foci in
      the lungs. In the course of further attempts to transfer the passage strain, a
      secondary infection by a bacillus of the paratyphoid group caused many deaths
      among the guinea pigs and resulted finally in the loss of the strain from Case 1.
      Most of the cultures made with the heart's blood taken at autopsy from Case 1
      proved to be contaminated with a bacillus of the coli group. The contents of the
      apparently uncontaminated tubes were inoculated into guinea pigs, but the results
      were for the most part negative or vitiated by a secondary infection. Dark-field
      search for the leptospira with the autopsy materials was negative, although
      prolonged and thorough examination was not practicable at the time of these
      experiments. Our efforts were concentrated on obtaining positive animal
      transmission rather than on the time-consuming demonstration of the leptospira,
      which when unsuccessful does not necessarily exclude the presence of the organism
      in small numbers. Likewise, the dark-field work with the material from guinea
      pigs was confined to a brief examination and was omitted in many instances. Under
      these circumstances no leptospira was encountered in any of the material from
      Case 1. On the other hand, the results obtained with the specimens of blood from
      Case 2 were definitely positive, not only in the transmission of the disease
      directly, or indirectly by means of cultures, into guinea pigs, but also in the
      demonstration of the leptospira in the primary cultures and in the blood and
      organ emulsions of guinea pigs experimentally infected with such cultures.
      Definite positive direct transmissions were obtained with the specimens of blood
      drawn on the 2nd and 3rd days. No blood was taken on the 4th or 6th days. There
      were indications of abortive or mild leptospira infection in the guinea pigs
      inoculated with the blood taken on the 5th day. Regarding the inoculation of
      cultures from Case 2, it may be stated that only the cultures (leptospira +) made
      with the blood drawn on the 2nd day caused a definite fatal infection in guinea
      pigs. From this series a continuous passage in the guinea pig has been
      successfully accomplished. One of the guinea pigs (No. 48) inoculated with the
      culture 5 days old (leptospira +) made from the blood taken on the 3rd day
      presented typical symptoms, and a positive transfer from this to another animal
      (No. 98) was also made. Cultures of the blood drawn on the 5th and 7th days gave
      unsatisfactory results, owing to a secondary contamination. Leptospiras were
      detected in some of the culture tubes containing 2nd and 3rd day specimens of
      blood from Case 2; they were few in number and for the most part immotile, owing
      perhaps to some unfavorable cultural condition such as a fungus contamination.
      Charts 17, 18, and 19 give a summary of the experiments. See PDF for Structure.

PMID- 19868465
TI  - IMMUNOLOGICAL STUDIES WITH A STRAIN OF LEPTOSPIRA ISOLATED FROM A CASE OF YELLOW
      FEVER IN MERIDA, YUCATAN.
AB  - Identification of the leptospira isolated from a case of yellow fever in Merida
      was accomplished by means of an anti-icteroides immune serum prepared in a horse
      with several Guayaquil strains of Leptospira icteroides. The immune serum showed
      a protective action of high titer against the Merida strain, thus establishing
      its efficacy as a therapeutic agent against this strain. Polyvalent anti
      icteroides immune serum prepared in the horse or monovalent anti-icteroides
      immune serums prepared in the rabbit had a definite devitalizing action upon the
      Merida strain, while immune serums similarly prepared with strains of
      icterohoemorrhagioe had no perceptible effect upon the Merida strain. Serums from
      yellow fever convalescents in Merida gave a positive Pfeiffer reaction with the
      Merida strain of Leptospira icteroides. The reactions between the Guayaquil
      strains (Nos. 1 and 5) and two of these serums from convalescents varied from
      definitely positive to doubtful, owing probably to the diminution of active
      immune principles in the serums during the prolonged and unfavorable conditions
      of their transportation.

PMID- 19868466
TI  - BIOLOGICAL AND PHYSICAL PROPERTIES OF THE HEMOTOXIN OF STREPTOCOCCI.
AB  - The hemotoxin of streptococcus is a labile substance affected by centrifugation
      or shaking. It is adsorbed by various organic and inorganic substances. Hemotoxin
      is produced within a wide range of hydrogen ion concentrations. It is neither in
      nor on the bacterial cell but is free in the culture medium. It is probably not
      an enzyme. There are at least two substances which are essential to the medium
      for the elaboration of hemotoxin, one of which is phosphorus; the other is a
      substance of unknown composition. The unknown component is present in small
      quantities in unfiltered muscle infusion, but is more abundantly supplied by
      blood serum and kidney infusion. This substance is not an albumin, globulin,
      primary or secondary proteose, metaprotein, or peptone of the medium or enriching
      fluid. It is water-soluble, is destroyed by boiling in alkaline solution and by
      prolonged heating, and is removed to a considerable extent by passage through a
      diatomaceous filter.

PMID- 19868467
TI  - DIVISIONS OF THE SO CALLED FLEXNER GROUP OF DYSENTERY BACILLI.
AB  - From these data it is seen that ill defined divisions of the so called Flexner
      group exist. The divisions do not appear to be sufficiently distinct to warrant
      the use of separate names. To avoid confusion all mannitol-fermenting dysentery
      bacilli should be called Bacillus dysenteriae Flexner and the subdivision noted.
      There are two methods for this division, one by the fermentation of
      carbohydrates, the other by agglutination with monovalent rabbit sera. These do
      not coincide and one or the other and not both must be adopted. Inasmuch as
      Murray studied organisms from widely distributed sources, it would seem
      preferable to adopt his serological classification and to add to it the types
      that fail to be agglutinated by his V, W, X, Y, and Z sera, as this method is
      simpler and more rapid. The results of the agglutination reactions of the
      patient's serum may be expressed in the same terms as the serological typing of
      the organism from his stool. Fermentation is less constant and gives rise to more
      divisions than there are carbohydrates. See PDF for Structure The serological
      reactions of these type sera, as Murray points out, show cross-agglutination to a
      greater or less extent, but they indicate that there are five antigens, V, W, X,
      Y, and Z and probably others, one or more of which predominate in a given strain.
      Polyvalent diagnostic and therapeutic sera are practically worthless unless they
      include antibodies for the more common of these types. The diagnostic importance
      of recognizing that there are five or more antigens in this group is seen from
      the fact that the sera of some patients react with one, others with another, and
      that unless several antigens are used, some positive tests may be missed. The
      therapeutic importance is emphasized by the fact that probably the best
      polyvalent therapeutic serum at present available has a very low titer for the X
      antigen, although that type was found in many of these cases (Table V).

PMID- 19868468
TI  - BIOLOGICAL STUDY OF THE HEMOPHILIC BACILLI.
AB  - 1. The hemophilic bacilli can be divided into two large groups according to the
      ability of certain strains to produce hemolysis. 2. Both the hemolytic and the
      non-hemolytic groups may be further subdivided according to the ability of some
      strains to produce indole, to form gas, and to ferment certain carbohydrates. 3.
      The hemophilic bacilli of both the hemolytic and the non-hemolytic varieties when
      grown in meat infusion broth containing 1 per cent of dextrose reach a final
      hydrogen ion concentration of about pH 6.4. In addition, practically all the
      strains possess the power to reduce nitrates to nitrites.

PMID- 19868469
TI  - FURTHER STUDIES ON THE ETIOLOGICAL ROLE OF VIBRIO FETUS.
AB  - The data bearing on these three cases are quite sufficient to rule out Bacillus
      abortus as the agent. Not only the cultures and guinea pig tests of fetal tissues
      and contents of the digestive tract, but also the agglutination and guinea pig
      tests of the milk, were negative. The same is true of the agglutination tests of
      the blood serum. Only in one case was the placenta obtained in part. The stained
      films and the sections from various regions showed no abortion bacilli. Guinea
      pig tests of placental tissue were negative for Bacillus abortus. On the other
      hand) minute organisms resembling vibrios were detected in the cytoplasm of
      endothelial cells within capillaries in the edematous subchorionic tissue.
      Subsequently the agglutination titer of the blood serum of one of these cases
      rose to a level indicating infection with Bacillus abortus during the second
      pregnancy. The peculiar distribution of abortions due to Vibrio fetus among older
      cows and heifers in this herd, resulting at first in cases among older cows and
      latterly passing to young stock, may be explained by certain occurrences in the
      herd itself. It may be assumed that the infection was originally brought in by
      purchased cows. The young stock is kept segregated from these in a special barn,
      and when 6 months old it is pastured on outlying farms until returned in an
      advanced stage of pregnancy. The heifers during the first pregnancy were thus
      kept away from vibrio carriers until after the first calf was born. In June and
      July, 1919, 55 older cows, purchased and native, were placed on the young stock
      pasture. The three cases of abortion in heifers due to Vibrio fetus occurred
      October 24, November 9, and December 2, 1919. The age and condition of the
      fetuses accord very well with the assumption that Vibrio fetus was introduced
      among the young stock in June or July of the same year. The information gathered
      thus far concerning vibrionic abortion in this herd enables us to formulate a
      tentative hypothesis subject to modification with increasing knowledge of this
      type of infectious abortion. The infectious agent was probably introduced by
      purchased cows in 1917 or earlier. It gained a certain headway up to 1919, then
      the number of cases declined so that between May, 1919, and May, 1920, only the
      above three cases in heifers, and one case of mixed infection with Bacillus
      abortus in an older cow, were detected. During the same period cases due to
      Bacillus abortus continued undiminished. The greater resistance of Bacillus
      abortus manifested in cultures as compared with Vibrio fetus is thus reflected in
      its behavior in nature. The temporary dying out of the infection indicates that
      natural immunization of a herd to Vibrio fetus proceeds quite rapidly. Another
      outbreak may be expected when the immunity of the herd has declined in the
      absence of the infecting agent and the latter is reintroduced from without, or it
      may reappear at any time when a vibrio of higher virulence is brought in.

PMID- 19868470
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : IX. PRODUCTION IN MONKEYS OF AN ACUTE
      RESPIRATORY DISEASE RESEMBLING INFLUENZA BY INOCULATION WITH BACILLUS INFLUENZAE.
AB  - Twelve normal monkeys inoculated on the mucous membranes of the nose or nose and
      mouth with a strain of Bacillus influenzae; originally isolated in pure culture
      from the pleural exudate of a case of empyema following influenzal pneumonia in
      man and subsequently raised in virulence by animal passage, developed an acute
      self-limited respiratory disease of from 3 to 5 days duration, characterized by
      sudden onset with profound prostration, the development of rhinitis and
      tracheobronchitis, with sneezing, cough, and the outpouring of a scanty mucoid,
      or mucopurulent exudate, a variable febrile reaction, and either a leucopenia or
      no significant change in the leucocyte count. This disease was complicated in
      five instances by purulent sinusitis of one or both antra, in three by
      bronchopneumonia. Bacillus influenzae was recovered at autopsy from the lesions
      of the disease either in pure culture or in association with organisms that are
      normal inhabitants of the upper respiratory tract of monkeys. Of ten normal
      monkeys injected intratracheally with the same strain of Bacillus influenzae,
      seven developed bronchopneumonia, two developed tracheobronchitis without
      pneumonia, and one resisted infection. The general symptoms and duration of the
      disease were similar to those of the preceding group. There were a severe cough
      and accelerated respirations. Bacillus influenzae was recovered in pure culture
      from the lungs, bronchi, or trachea in the animals killed during the active stage
      of the disease. It disappeared promptly from the respiratory tract with recovery.
      The significance of the first series of experiments in which monkeys were
      inoculated in the upper respiratory tract is twofold. First, they establish the
      fact that Bacillus influenzae can initiate in monkeys an acute infection of the
      normal mucous membranes of the upper respiratory tract; that is, it can act as a
      primary incitant of respiratory infection without the assistance of a preceding
      or concomitant contributing cause. In this respect it differs radically from the
      pneumococcus and Streptococcus haemolyticus, since experiments previously
      reported(2, 4) have shown that neither of these organisms possesses the property
      of initiating an infection of the normal mucous membranes of the upper
      respiratory tract of monkeys, even though the strains used were incalculably more
      virulent for monkeys than the strain of Bacillus influenzae used in the foregoing
      experiments. Secondly, the experiments show that Bacillus influenzae infection of
      the mucous membranes of the upper respiratory tract may spread by continuity to
      the paranasal sinuses, setting up an acute sinusitis, that it spreads readily to
      the lower respiratory tract, producing a tracheobronchitis and permitting the
      ready invasion of secondary bacteria, and that it may penetrate as far as the
      terminal bronchioles, alveolar ducts, atria, and alveoli, there setting up a
      bronchiolitis and true bronchopneumonia. In these respects it likewise differs
      radically from the pneumococcus and Streptococcus haemolyticus which do not
      possess these pathogenic properties as previous experiments have shown.(2, 4) The
      bearing of these facts on the possible etiologic relation of Bacillus influenzae
      to influenza is important, since they show that Bacillus influenzae possesses
      certain definite primary pathogenic properties which distinguish it and therefore
      separate it from the group of recognized secondary organisms in influenzal
      complications, of which the pneumococcus and the streptococcus are the most
      frequent. The possible etiologic relation of Bacillus influenzae to influenza is
      further supported by the character of the respiratory disease that occurred in
      the monkeys. The sudden onset with profound prostration, the absence of
      leucocytosis or often a leucopenia, the congestion of the mucous membranes of the
      respiratory tract, the development on the 2nd or 3rd day of an irritative cough
      due to an inflammatory tracheitis or tracheobronchitis, the brief self-limited
      course of the infection, and the irregular febrile reactions are all
      characteristic of influenza. Many of these symptoms were in striking contrast
      with the symptoms and course of pneumococcus or streptococcus infections in
      monkeys in which there were no prostration at onset, invariable leucocytosis, and
      infrequent cough developing only late in the disease. While all the above
      features of the disease produced in monkeys are characteristic of influenza in
      man, none are pathognomonic and, in fact, it is doubtful whether uncomplicated
      influenza possesses any pathognomonic features by which it may be diagnosed
      certainly in the absence of an epidemic. Even during epidemic times many
      respiratory infections arise which, though presumably influenza, it is impossible
      to diagnose as such with certainty. Nor does pathology help in this respect,
      since there would appear to be no established distinctive lesions of
      uncomplicated influenza in man, nor for that matter of the complications of
      influenza, apart from the complications which have been ascribed by Pfeiffer,(5)
      MacCallum,(6) Wolbach,(7) and others to infection with Bacillus influenzae
      because of the association of Bacillus influenzae in pure culture with these
      complications. For these reasons, although the disease produced in monkeys
      appears to be essentially identical with influenza in man with respect to its
      clinical course and complications, it is impossible to determine certainly
      whether it is actually so. The experiments are advanced, therefore, as evidence
      in favor of the etiologic relation of Bacillus influenzae to influenza, though
      they do not permit of a definite conclusion in this respect. Their bearing upon
      the relation of Bacillus influenzae to certain of the complications of influenza
      would appear to be reasonably conclusive. The recovery of Bacillus influenzae in
      pure culture at autopsy from the antra, from the trachea and bronchi, and from
      the lungs in some of the animals developing sinusitis, bronchiolitis, and a
      characteristic type of bronchopneumonia confirms by animal experiment the
      etiologic relation of Bacillus influenzae to these complications of influenza,
      which hitherto has rested solely upon the frequent association of the influenza
      bacillus with these lesions in man. The production of tracheobronchitis and the
      same type of bronchopneumonia by the intratracheal injection of Bacillus
      influenzae in the second series of experiments serves as additional confirmation
      of this, but has no direct bearing on the etiologic relation of Bacillus
      influenzae to uncomplicated influenzae.

PMID- 19868471
TI  - STUDIES ON EXPERIMENTAL PNEUMONIA : X. PATHOLOGY OF EXPERIMENTAL INFLUENZA AND OF
      BACILLUS INFLUENZAE PNEUMONIA IN MONKEYS.
AB  - 1. Virulent influenza bacilli, when injected into the nose and throat of monkeys
      (Cebus capucinus and Macacus syrichtus), excite an acute inflammation of the
      upper respiratory tract, characterized by swelling and hyperemia of the mucous
      membrane, infiltration of the mucosa and subrnucosa with leucocytes, desquamation
      of epithelial cells, and the production of a mucopurulent exudate. The accessory
      sinuses are often implicated in the infection. 2. Experimental Bacillus
      influenzae infections of the upper respiratory tract are frequently accompanied
      or followed by bronchiolitis, peribronchial infiltration, and bronchopneumonia
      with hemorrhage and edema in the early stage, emphysema and bronchiectasis in the
      later stages. In general, the process closely resembles uncomplicated Bacillus
      influenzae pneumonia in man. 3. The injection of virulent influenza bacilli
      directly into the trachea of monkeys induces in them an experimental
      bronchiolitis and hemorrhagic bronchopneumonia, similar in all respects to
      spontaneous Bacillus influenzae pneumonia. 4. In experimental Bacillus
      influenzaeinfections of either the upper or lower respiratory tract the influenza
      bacillus can usually be recovered during .the acute stage by culture, either pure
      or in association with other bacteria. 5. In experimental Bacillus influenzae
      infections in monkeys characteristic changes occur in the thymus gland
      hyperplasia of the follicles, distention of the lymphatic channels, and
      infiltration of the parenchyma with leucocytes. This enlargement appears to be
      merely part of a general hyperplasia of the lymphoid structures in the cervical
      and thoracic regions.

PMID- 19868472
TI  - EXPERIMENTAL STUDIES ON HETEROPLASTIC BONE FORMATION.
AB  - 1. Bone formation in the rabbit kidney with ligated vessels takes place (a)
      through the activity of young fibroblasts which accumulate to form a membrane
      like structure; (b) subsequently by direct ossification of hyaline connective
      tissue in continuity with preformed bone; and (c) through erosion of lime
      placques by granulating tissue and laying down of lamellar bone by cells derived
      from fibroblasts. 2. Bone formation in the rabbit kidney begins not in direct
      contact with calcium deposits, but in the loose vascular connective tissue close
      under the transitional epithelium of the calices. 3. With autotransplanted ear
      cartilage of the rabbit there is an active new formation of cartilage in the
      connective tissue which surrounds the transplants, and the bone is formed by the
      fibroblasts from the perichondrium which erode and invade the calcified areas in
      this new cartilage. 4. The process of bone formation in the kidney is similar to
      that found in normal membranous ossification, while with the transplanted ear
      cartilage the process is identical with endochondral ossification.

PMID- 19868473
TI  - SIMPLIFIED PRODUCTION OF ANTIMENINGOCOCCIC SERUM.
AB  - In an attempt to simplify the manufacture of an efficacious antimeningococcus
      serum an experimental study has been made of a number of sera produced with a few
      or with single strains of meningococcus, the therapeutic polyvalent serum
      produced at The Rockefeller Institute with more than 50 strains being used as a
      standard of comparison. It was found that horses injected with an antigen limited
      to five, three, or even one strain yielded sera with a range of agglutinins
      covering in high dilution practically all the stock strains used in producing the
      polyvalent serum. These sera appeared to equal the polyvalent serum in range and
      titer of agglutinins, but on further examination fundamental differences were
      found. Storage for a year had little effect upon the titer and inclusiveness of
      the polyvalent serum, whereas the monovalent serum had fallen off greatly,
      especially in regard to secondary or subsidiary agglutinins, so that only a
      comparatively small number of stock strains was still agglutinated. The serum
      made with five strains, a regular, a para, and three intermediate meningococci,
      approached the polyvalent serum in keeping qualities and still agglutinated at
      the end of this period 39 of the 41 strains tested. Absorption tests also brought
      out inherent differences in the nature of the polyvalent and the monovalent sera
      which had appeared to be practically identical in simple agglutination tests. The
      homologous strain on triple absorption was able to exhaust the monovalent serum
      completely, but was unable to remove from the polyvalent serum agglutinins to
      which 30 of 44 different strains were able to react. Absorption with another
      single strain of the same type removed from the monovalent serum agglutinins for
      a majority of the test strains but left the polyvalent serum relatively
      unaffected. It is comparatively easy to produce a serum effective against about
      80 per cent of the spinal strains of meningococci encountered. Deficiencies in
      our knowledge of the antigenic capacities of the meningococcus have led to the
      more or less empirical use of a large number of cultures in the preparation of a
      serum effective against the remaining 20 per cent of the strains. How far the
      number of the latter in the antigen may be reduced without restricting the
      efficacy of the serum remains yet to be determined. However, the experimental
      evidence recorded here apparently does not favor the use of an antigen limited to
      one or too few strains. For example, three or five selected strains produced a
      serum which agglutinated practically all the strains against which it was tested.
      But in view of the many observations which point to the greater therapeutic
      efficacy of a serum made with a larger number of strains we would not as yet
      advocate a serum prepared with too limited antigens even though it contains at
      first a wide range of agglutinins. It has been brought out that a monovalent
      serum contains, in addition .to specific agglutinins, a wide range of common or
      secondary agglutinins which tend to disappear during storage. The difference
      between specific and secondary agglutinins is not apparent in simple
      agglutination tests, but is revealed by absorption tests. It is probable that in
      a serum prepared with a few strains the same condition exists, whereas in a serum
      produced with a large number of strains the agglutinins are mainly specific as
      contrasted with the fact that most of them are secondary in the serum produced
      with few strains. The question whether secondary agglutinins are therapeutically
      equivalent to primary or specific agglutinins requires further study.

PMID- 19868474
TI  - THE RETICULAR MATERIAL OF DEVELOPING BLOOD CELLS.
AB  - Erythroblasts, leucocytes, and lymphocytes resemble other cells of the body in
      containing a restricted area of fluidity in their cytoplasm. In special
      preparations this fluid appears in the form of a more or less complicated
      reticulum which seems to be continually but slowly changing in shape. For
      convenience the fluid may provisionally be referred to as reticular material,
      emphasis being laid on its composition rather than its form. As a working
      hypothesis it is safe to assume that the chemical and physical properties of this
      material vary in cells of different kinds as well as in different stages in the
      activity of the same cell. The conclusion that it is "identical" in different
      cells, because the present crude methods of technique reveal no fundamental
      differences, would be as incorrect as the statement that the serum of different
      animals is identical, because no difference is observed on microscopic
      examination.

PMID- 19868475
TI  - COMPARISON OF THE POTENCY OF POLYVALENT ANTIMENINGOCOCCUS SERUM PRODUCED WITH
      FOUR AND SIX REPRESENTATIVE STRAINS AND THAT PRODUCED WITH SIXTY STRAINS, AS
      DETERMINED BY THE AGGLUTINATION TITER.
AB  - The potency of a polyvalent antimeningococcus serum, as tested by its
      agglutination titer, was sacrificed by immunization with a large number of
      strains of the meningococcus. By immunization with a limited number of
      representative strains, four or six, carefully selected on account of their
      antigenic and agglutination properties, the potency was increased three- to
      tenfold without sacrificing the polyvalency; that is, as tested with at least 70
      heterologous strains of the meningococcus. The agglutination titer,
      unfortunately, is not an entirely satisfactory criterion of therapeutic potency,
      but it is the only practical method available that determines also the polyvalent
      action of antimeningococcus serum.

PMID- 19868476
TI  - PURIFICATION AND CONCENTRATION OF ANTIGENS FOR COMPLEMENT FIXATION BY METHODS OF
      DIALYSIS, ADSORPTION, AND EXTRACTION.
AB  - Antigens were prepared from the culture filtrates of tubercle bacilli and by
      extraction of washed and dried organisms with organic and aqueous solvents and
      from tissues of organs showing tuberculous lesions. A comparison of these
      preparations by means of the complement fixation test showed that the aqueous
      extracts were most active antigenically. The antigenic activity of the aqueous
      preparations and also of the slightly active culture filtrates was increased by
      means of dialysis and adsorption with serum globulin followed by extraction with
      alcohol and concentration of the alcoholic extract in vacuo.

PMID- 19868477
TI  - STREPTOCOCCI OCCURRING IN SOUR MILK.
AB  - A well defined group of rod-like and coccoid organisms arranged in pairs and
      chains has been encountered in sour milk. The group comprises at least three
      species; the largest number ferment dextrose, lactose, maltose, mannitol, and
      salicin, and fail to ferment saccharose, raffinose, and inulin. A smaller number
      ferment saccharose in addition to dextrose, lactose, maltose, mannitol, and
      salicin. A few fail to attack mannitol. All three types grow luxuriantly at room
      temperature, coagulate milk, reduce litmus, and produce large amounts of acid in
      fermented bouillon containing dextrose. Specific morphological and cultural
      differences exist between the lactic acid streptococci and those associated with
      mastitis and those occurring in the udder. The lactic acid organisms outgrow the
      udder streptococci in the milk-souring process. When both types are implanted in
      sterile milk the udder type soon disappears.

PMID- 19868478
TI  - PREPARATION OF COLLODION SACS FOR USE IN BACTERIOLOGY.
AB  - A standardized method is described in detail by which collodion sacs suitable for
      intraperitoneal incubation and for other bacteriological experiments may be
      produced in large numbers, sterilized, and handled with convenience and the
      minimum danger of contamination. Various factors influencing permeability have
      been subjected to experiment. Like Brown, we found that immersion in alcohol is
      the most important factor, but the high permeability conferred by alcohol
      treatment is lost during heat sterilization if the membrane was previously
      allowed to dry. Quantitative experiments on the dialysis of sodium chloride, and
      simple tests with other substances indicate the general character of the
      membranes and their probable field of usefulness in bacteriology.

PMID- 19868479
TI  - A MECHANICAL MEASURING INSTRUMENT FOR STERILE LIQUIDS.
AB  - An instrument is described by which aliquot portions of a liquid may be
      mechanically measured and delivered. It was devised especially for use in
      immunological experiments, to take the place of a graduated pipette in setting up
      serum tests. The instrument may be set for any quantity within its capacity and
      measures sterile liquids without danger of contamination. It may therefore find a
      wider application in other procedures requiring sterile measurements of small
      amounts of liquid.

PMID- 19868480
TI  - FACTORS INFLUENCING ANAEROBIOSIS, WITH SPECIAL REFERENCE TO THE USE OF FRESH
      TISSUE.
AB  - This study was undertaken with the object of determining the part played by the
      several component elements of the tissue method of anaerobic cultivation in the
      establishment of anaerobic conditions in the culture tube. Data have been
      presented to show the suitability of methylene blue as an indicator of reduction
      processes in culture media by which the removal of the last traces of oxygen may
      be demonstrated. With methylene blue as the indicator, the elements subjected to
      experiment included the choice of a seal for culture tubes, the activity and
      requisite size of the kidney tissue fragment, the chemical and physical
      characters of the medium which promote or retard deoxygenation, the length of the
      column of medium, and the advantages of external aids such as the McIntosh and
      Fildes anaerobic jar. As a result of our experiments, we have come to the
      following conclusions: 1. Liquid paraffin oil, used extensively as a seal for
      anaerobic cultures and in gas analysis, has very little value in inhibiting the
      access of oxygen. Solid vaseline, on the other hand, forms an effective oxygen
      resisting seal. The difference is due to the physical states of the substances at
      incubator temperature. 2. Fresh kidney tissue is an active reducing agent and
      quickly decolorizes methylene blue in its vicinity. The reducing effect of fresh
      kidney tissue is relative to the amount used. As a reducing agent, at least 0.6
      gm. per tube is required for the establishment of an adequate oxygen-free zone.
      3. Culture media may be classified as reducing or non-reducing. Those containing
      dextrose or peptone in a faintly alkaline solution belong to the former class.
      Ascitic fluid and dilute serum belong to the latter class, for their content of
      reducing substances is practically insignificant. For the prompt establishment of
      strictly anaerobic conditions these media require the addition of reducing
      substances such as dextrose, peptone, or kidney tissue aided by an effective seal
      or an anaerobic jar. 4. Semisolid media effectively inhibit the penetration of
      oxygen to the depths of the tube, but they likewise limit the diffusion of
      reducing substances and presumably of nutrient substances from imbedded kidney
      tissue. 5. The length of the column of medium is of minor importance under a
      vaseline seal. We clearly recognize the impracticability of standardizing a
      biological technique which by its very nature must be subject to wide
      modifications for special purposes. Such variations from a standard are
      especially necessary in the search for unknown organisms, and in work with
      hitherto uncultivated microbes in which the tissue technique has been
      successfully applied by Noguchi. We wish, therefore, to present the results of
      our studies simply as guides in the variation and control of the elements
      examined and to make certain suggestions relative to the establishment of
      strictly anaerobic conditions in the culture tube. The numerous other factors of
      equal importance which must be taken into account-hydrogen ion concentration,
      source and character of nutritive elements, temperature, time, etc.-are outside
      the limited scope of the present report. For the establishment of strictly
      anaerobic conditions in the culture tube, we would suggest (1) the substitution
      of solid vaseline for liquid paraffin oil as an oxygen-resisting seal; (2) the
      use of large pieces of fresh kidney, the standard size to be upwards of 0.6 gm.
      unless other reducing substances are present in the medium; (3) the addition of
      peptone or dextrose or both in the form of peptone dextrose broth in fractional
      percentages to non-reducing media such as ascitic fluid or serum to aid in the
      prompt establishment of anaerobic conditions; (4) the use of the McIntosh and
      Fildes jar as a further aid to the prompt deoxygenation of the medium; (5) for
      reasons of economy the use of smaller amounts of culture medium, for example, 7
      to 8 cc., under a vaseline seal; and (6) in dealing with anaerobes which may be
      injured by exposure to oxygen it might be advisable to prepare the medium a day
      or two in advance and to incubate it under a vaseline seal so that sterility is
      assured and the anaerobic conditions are already established when inoculation is
      made. The infected material is then introduced with a capillary pipette in the
      vicinity of the kidney tissue and the seal restored by gentle heating to melt a
      portion of the superposed vaseline.

PMID- 19868481
TI  - PRESERVATION OF STOCK CULTURES OF BACTERIA BY FREEZING AND DRYING.
AB  - Attention is called to the fact that bacteria may be preserved for a long time by
      desiccation in the frozen state. It has been shown that it is necessary to
      maintain the frozen condition until desiccation is complete; if the fluid melts
      before the moisture is completely removed, the organisms are killed, probably
      because of the concentration of the salts upon the surface of the bacteria. By
      the simple expedient of immersing the tubes of organisms in glycerol contained in
      a desiccator and subsequently keeping the whole apparatus in a salt-ice mixture
      until drying is complete, the organisms are easily maintained in the frozen
      state, and dry properly. Bacteria preserved in this manner retain their cultural,
      biochemical, and immunological characters for prolonged periods.

PMID- 19868482
TI  - QUANTITATIVE DISTRIBUTION OF PARTICULATE MATERIAL (MANGANESE DIOXIDE)
      ADMINISTERED INTRAVENOUSLY TO THE CAT.
AB  - 1. Manganese dioxide suspended in an acacia-sodium chloride solution provides a
      non-toxic injection which in the present experiments has contained no particles
      larger than 1micro and which, when deposited in the body, can be determined
      quantitatively and seen microscopically. 2. Intravenous injections have been made
      under precautions which preclude removal from the blood or deposition in organs
      through simple capillary blockage. 3. In nine experiments out of thirteen the
      circulating blood contained no manganese after 18 minutes. In the four remaining
      instances there was a steady slight elimination which was incomplete at the end
      of 1 hour. Within certain limits the rate of removal from the circulating blood
      and the sites of deposition in the animal are not influenced by the concentration
      of the suspension, the blood pressure, or antecedent introduction of acacia or
      histamine. 4. In the cat amounts of manganese dioxide varying between 9.8 and 3.9
      mg. of manganese and containing from 50,000,000,000 to 10,000,000,000 particles,
      if injected intravenously, permit recovery at the end of 1 hour of 90 per cent of
      the material in the lungs, liver, and spleen in the following proportions: lungs
      47 per cent; liver 38.3 per cent; spleen 4.3 per cent. 5. These experiments,
      coupled with correlative results by other investigators, make it clear that in
      certain organs-the lungs, liver, and spleen of the cat-the vascular endothelium
      possesses phagocytic power rendering the capillaries permeable to particulate
      material as well as to gases, liquids, and dissolved substances.

PMID- 19868483
TI  - STUDY OF THE CLASSIFICATION OF MENINGOCOCCI.
AB  - The meningococcus, like some other pathogenic species, varies in its
      agglutination in immune serum, some strains being readily agglutinable while
      others agglutinate with difficulty in their homologous serum as well as in
      heterologous serums. The different strains appear to vary also in their action as
      antigens. In order to secure representative strains, therefore, it was thought
      necessary to consider the antigenic action as well as the agglutinability of the
      cultures.

PMID- 19868484
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      I. TRANSMISSION EXPERIMENTS WITH NASOPHARYNGEAL WASHINGS.
AB  - An active substance has been detected, by the methods described, in five patients
      in early stages of epidemic influenza during 1918-19 and two patients in early
      stages of epidemic influenza during 1920 It was not detected in twelve cases of
      the same disease in which the onset of obvious symptoms occurred more than 36
      hours before washing of the nasopharynx was carried out, nor was it found in the
      secretions of fourteen individuals free from the syndrome of influenza either
      during the epidemics or the interval between them. With this substance a clinical
      and pathological condition has been induced in rabbits, affecting the blood and
      pulmonary structures mainly, which could be maintained and carried through at
      least fifteen successive animals. For this reason, and also because of the
      dilution between passages, we are led to believe that we were dealing with the
      actual transmission of a multiplying agent rather than with a passive
      transference of an original active substance. In some of the experiments
      secondary infections by ordinary bacteria were encountered. The relation of these
      microorganisms to this active substance will be dealt with fully in another
      communication. However, the essential effects were produced by a substance wholly
      unrelated to these bacteria. The similarity that exists between the effects
      produced in rabbits on the blood and the lungs and those occurring in man in
      epidemic influenza provides a basis for further investigation on the inciting
      agent of epidemic influenza.

PMID- 19868485
TI  - CHILOMASTIX MESNILI AND A METHOD FOR ITS CULTURE.
AB  - 1. Cases of flagellate infection of man by Chilomastix mesnili have been reported
      from nearly every locality in the world. They are fairly abundant in the United
      States and are often confused with cases of infection by Trichomonas
      intestinalis. 2. The shape of Chilomastix is pyriform. The body contains the
      following structures: nucleus, centrosome, primary, secondary, and tertiary
      blepharoplasts, parabasal, parastyle, peristomal fiber, ventral cytostome,
      cytostomal flagellum, three anterior flagella, food vacuoles with bacterial
      inclusions, and a posterior spine-like process, the hold-fast organ. 3. The
      twisted shape in some flagellates in this case of infection is a temporary
      condition. It was seen in flagellates taken from the feces of the patient on only
      two occasions and was never observed among the cultured forms. 4. The cysts of
      Chilomastix are lemon-shaped and occurred irregularly in the stools of the
      patient. They have not been encountered thus far in the cultures. 5. Chilomastix
      mesnili was cultured continuously from January 27 to June 15, 1920, in an
      artificial medium composed of one part of human serum and four parts of Locke's
      solution with the addition of a small amount of dextrose. 6. Cultures sometimes
      remained viable for a period of 1 to 10 days, but generally for a period of 1 to
      8 days. 7. The flagellates in the cultures increased in number during the 1st,
      2nd, 3rd, and often the 4th days, after which there was a decrease until all had
      disappeared. 8. A period of lag, probably 13 hours in length, and followed by a
      period of great fecundity, characterized the growth of the flagellates during the
      1st day in the cultures. 9. The number of flagellates in the cultures varied
      considerably and often reached 700,000 per cubic centimeter. 10. The bacteria
      served in part as the food of the flagellates. The bacterial organisms identified
      in the cultures were Bacillus coli communis, Bacillus coli communior, Bacterium
      aerogenes, Bacillus alkaligenes, and Bacillus proteus. The proteins of the blood
      serum, the mineral salts, and the dextrose in the medium may also have proved a
      source of food for the protozoa. 11. The products of bacterial metabolism,
      resulting from the growth of the bacteria, their fermentative activity, and their
      death may explain the rate of growth, reproduction, and death of the flagellates
      in the cultures. A certain amount of the products of decomposition together with
      the presence of the bacterial food supply may explain the rapid proliferation of
      the flagellates during the 1st day and the slower rate up to the 3rd or 4th day.
      An excess of these products may have inhibited the growth and multiplication of
      the protozoa, especially after the 3rd or 4th day, and ultimately may have
      brought about their death and disappearance from the cultures. 12. The initial
      alkalinity of the medium increased at the death of the culture. It is not
      believed that the change in alkalinity proved lethal to the protozoa. 13. Binary
      fission was often observed. The plane of division was median and longitudinal. A
      paradesmose was formed. 14. Multiple fission also occurred. The flagellate body,
      ameboid in movement, was a somatella comprised of four zooids. It contained four
      cytostomes, each with a cytostomal flagellum. The number of anterior flagella was
      not complete for each zooid. 15. Flagellates, joined in pairs, were often seen
      during the first 3 days in the cultures. They may represent conjugating forms,
      but as yet no evidence of the exchange of nuclear substance has been seen.

PMID- 19868486
TI  - MECHANISM OF UREA EXCRETION.
AB  - 1. Urea is present in the cells of the proximal convoluted tubule in a
      concentration higher than that of the blood or than that of the cells of any of
      the other kidney tubules. 2. Such a condition can only be reconciled to an
      assumption of an active secretion (excretion) on the part of these cells. 3. Urea
      also passes through the glomerular filter with the other crystalloids of the
      blood plasma. 4. The final concentration of urea is due to the above mentioned
      secretion by the proximal convoluted tubule, and to the absorption of water in
      other parts of the tubule.

PMID- 19868487
TI  - IMMUNOLOGICAL DISTINCTIONS OF ENCEPHALITIS AND POLIOMYELITIS.
AB  - Lethargic encephalitis is an epidemic disease, the main manifestations of which
      relate to injury inflicted upon the central nervous system and in particular the
      basal ganglia of the brain. Poliomyelitis is an epidemic disease, the main
      manifestations of which relate to injury inflicted upon the central nervous
      system and in particular the gray matter of the spinal cord and medulla
      oblongata. At the outset of the epidemic of lethargic encephalitis the two
      diseases tend to prevail at distinct and different seasons of the year, although
      recently cases of epidemic encephalitis have arisen in the midsummer months. The
      two maladies therefore are perhaps less distinguished by seasonal prevalence than
      has been supposed. They are, however, distinguished by great differences in
      communicability to monkeys. Epidemic poliomyelitis is readily transmitted through
      inoculation of the affected central nervous tissues of man to monkeys, while it
      may still be regarded as doubtful whether lethargic encephalitis has been
      communicated to monkeys in this manner. As the experiments reported in this paper
      show, the two diseases can be distinguished through the power of blood serum
      under certain circumstances to neutralize the virus of poliomyelitis. The blood
      serum of convalescent cases of poliomyelitis whether in man or monkey possesses
      this neutralizing power, while the blood serum of recently convalescent cases of
      epidemic encephalitis is devoid of it. On the basis of the distinguishing
      characters described, it is regarded as desirable at the present time to hold
      epidemic poliomyelitis and epidemic encephalitis as integrally distinct
      affections. The latter also may be infectious, yet the main lesions of
      poliomyelitis are present in the spinal cord, and of epidemic encephalitis in the
      mid-brain.

PMID- 19868488
TI  - THERAPEUTIC ACTION OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID (TRYPARSAMIDE) UPON
      EXPERIMENTAL INFECTIONS OF TRYPANOSOMA RHODESIENSE.
AB  - A series of experiments was carried out to determine the effects of tryparsamide
      upon the infections produced in various species of animals by Tr. rhodesiense.
      The strain of trypanosome used was one which possessed a very low virulence for
      guinea pigs, was fairly virulent for mice and rats, and highly virulent for
      rabbits. Therapeutic experiments carried out on 24 hour infections in mice and
      rats showed that cures could be obtained in this class of infections by the
      administration of a single large dose of the drug amounting to approximately two
      thirds of the maximum tolerable dose, as contrasted with similar results in cases
      of gambiense infections from approximately one-ninth and one-fifth of this dose
      respectively. With advanced infections in rabbits, there appeared to be no single
      dose of the drug capable of insuring a cure which could be administered with
      safety, although some cures were obtainable with doses approximating the maximum
      tolerable dose. Treatment of these infections could be carried to a successful
      conclusion, however, by an intensive system of treatment in which large doses of
      the drug were administered at short intervals of time, and even relapses yielded
      to this treatment in some instances. The employment of such a method of treatment
      was possible on account of the unusual tolerance exhibited by animals to this
      drug, a fact which was previously emphasized.

PMID- 19868489
TI  - STUDIES OF THE ACID-BASE EQUILIBRIUM IN DISEASE FROM THE POINT OF VIEW OF BLOOD
      GASES.
AB  - Carbon dioxide diagrams (Haggard and Henderson (9)) have been constructed for the
      blood of a series of hospital patients as a method of studying disturbances in
      their acid-base equilibrium. A diabetic with a low level of blood alkali, but
      with a normal blood reaction, a compensated acidosis in other words, showed a
      rapid return towards normal with no treatment but fasting and increased water and
      salt intake. A nephritic with a decompensated acidosis and a very low blood
      alkali was rapidly brought to a condition of decompensated alkalosis with a high
      blood alkali by the therapeutic administration of sodium bicarbonate. It is
      suggested that the therapeutic use of alkali in acidosis is probably only
      indicated in the decompensated variety, and that there it should be controlled
      carefully and the production of alkalosis avoided. The diagram obtained in three
      pneumonia patients suggested that they were suffering from a condition of
      carbonic acidosis, due perhaps to insufficient pulmonary ventilation. In two out
      of three cases of anemia the dissociation curve was found to lie at a higher
      level than normal. No explanation for this finding was offered.

PMID- 19868490
TI  - RELATION BETWEEN THE VIRULENCE OF STREPTOCOCCI AND HEMOLYSIN.
AB  - Strains of streptococci whose virulence has been increased for any one species of
      animal do not produce greater concentrations of hemolysin than the original
      strain. Furthermore, there is a tendency for the original culture to grow more
      rapidly than the more pathogenic form, and to reach the height of hemolysin
      production at an earlier stage during the growth of the culture. These
      conclusions can probably be applied only to experiments in which the serum used
      in the media is from some species not employed for the animal passages.

PMID- 19868491
TI  - QUANTITATIVE DISTRIBUTION OF PARTICULATE MATERIAL (MANGANESE DIOXIDE)
      ADMINISTERED INTRAVENOUSLY TO THE DOG, RABBIT, GUINEA PIG, RAT, CHICKEN, AND
      TURTLE.
AB  - The distribution of manganese dioxide particles 1 hour following intravenous
      injection in cats, dogs, rabbits, guinea pigs, rats, chickens, and turtles is
      described. This distribution is remarkably constant for all the animals tested,
      except the cat, in which the injected material is practically equally divided
      between the lungs and liver. In the other animals the liver performs the main
      share of the work, and in the cat it has been shown that the liver after 12 hours
      accumulates the manganese which was formerly deposited in the lungs. The results
      are in harmony with experiments in which bacterial suspensions are employed for
      injection and confirm the suggestion previously made (2) that in the first
      handling of foreign particulate material the animal behaves similarly whether
      protein or inorganic injections are used.

PMID- 19868492
TI  - EXPERIMENTAL STUDIES ON YELLOW FEVER IN NORTHERN PERU.
AB  - Fourteen typical cases of yellow fever were studied in northern Peru during an
      epidemic occurring in 1920, nine in Payta in March and April, and five in
      Morropon and Piura in April and May. The method of investigation was similar to
      that previously employed, but as the laboratory facilities were very meager
      certain changes were required. Although in Payta the work was handicapped by the
      lack of electric light, the scarcity of water and animal food, the unsuitability
      of the guinea pigs for inoculation, and the changes in culture media due to age,
      the results obtained under these adverse conditions were by no means negative.
      While in no instance was there a typical infection produced in animals, either by
      direct inoculation of blood or with culture materials, yet certain guinea pigs in
      each series showed temporary febrile reactions or definite hemorrhagic lesions of
      the lungs indicative of a mild leptospira infection. Direct search for Leptospira
      icteroides in the blood of patients or in culture materials was not made because
      the dark-field microscope could not be used. Subsequently, at Piura, the
      laboratory facilities were vastly, improved, the use of the dark-field microscope
      was made possible by means of a storage battery, and a fresh stock of young
      healthy guinea pigs was received from New York, and fresh rabbit serum obtained
      in Piura. In the study of the materials obtained from five cases of yellow fever
      in Morropon all these added facilities were taken advantage of, with the result
      that the outcome was positive and convincing. Cultures from the five cases were
      examined after 11, 12, and 13 days, and in those from three cases living
      leptospiras were found. By inoculation into suitable guinea pigs of culture
      material from these five cases, irrespective of whether or not leptospiras were
      detected under the dark-field microscope, a typical Leptospira icteroides
      infection was produced from four of the five cases. In one of these no leptospira
      had been detected in the culture tubes. Thus one case only yielded negative
      results, in that no leptospiras were found under the dark-field microscope and
      the animal inoculation was negative. The leptospira was demonstrated in the blood
      or organ emulsions of the infected guinea pigs, and further transmission of each
      strain to other guinea pigs was obtained and pure cultures were secured. A few
      points of practical significance appeared in the course of the present
      investigation. One is the importance of using fresh rabbit serum for culture
      media. Old rabbit serum, whether in pure form or incorporated with agar, etc.,
      which had been kept for several months in a tropical climate, proved to be
      unsatisfactory for obtaining a growth of Leptospira icteroides. A second point of
      interest is the variation in susceptibility of guinea pigs to infection with
      Leptospira icteroides. In two of four series of positive animal inoculations with
      the Morropon culture materials only one-half of the guinea pigs inoculated with
      given materials developed typical symptoms. The other half either suffered from a
      transient mild infection, as evidenced by a few hemorrhagic foci in the lungs, or
      escaped infection altogether. From these facts it is highly probable that the
      lung lesions and febrile reactions observed in certain guinea pigs inoculated
      with the Payta materials were due to a mild leptospira infection. In a
      comparative experiment the native guinea pigs procured in Payta were found to be
      more resistant to the leptospira infection than those recently brought from New
      York. In fact, only a small portion of the former succumbed to typical infection
      even when inoculated with a virulent strain of Leptospira icteroides obtained
      from the Morropon epidemic. In conclusion it may be stated that of fourteen cases
      of yellow fever studied in Peru, a typical leptospira infection, together with
      the demonstration of the organism in experimentally infected guinea pigs, was
      obtained in four, while in the majority of instances indications of a mild, non
      fatal leptospira infection were observed. In a few cases only were the results
      entirely negative. The leptospira isolated from Morropon cases of yellow fever,
      which is morphologically and culturally identical with the Guayaquil and Merida
      strains of Leptospira icteroides, was also shown by immunity test to be
      indistinguishable from the Guayaquil organism.

PMID- 19868493
TI  - IMMUNOLOGY OF THE PERUVIAN STRAINS OF LEPTOSPIRA ICTEROIDES.
AB  - Serum from yellow fever convalescents from Payta, Piura, and Morropon gave a
      positive Pfeiffer reaction with the strains of Leptospira icteroides isolated in
      Guayaquil and Merida. The serum also protected the guinea pigs from these strains
      in the majority of instances. The Pfeiffer reaction was complete with all recent
      convalescents (7 to 36 days) but slight or partial in some instances with serum
      derived from individuals who had had the attack of yellow fever 10 months
      previously. The virulence of the Morropon strains was found to be approximately
      the same as that of the Guayaquil or Merida strains. With one strain the minimum
      lethal dose for the guinea pig was less than 0.00001 cc. of a kidney emulsion
      from an infected guinea pig. Suitable quantities of the anti-icteroides serum
      administered to guinea pigs inoculated with 2,000 to 20,000 minimum lethal doses
      of infective material prevented the development of the infection, or a fatal
      outcome, according as the serum was given during the incubation period or after
      fever had appeared. The earlier the administration of the serum the smaller was
      the quantity needed; during the incubation period 0.0001 to 0.001 cc. was
      sufficient, during the febrile period 0.01 to 0.1 cc. was required to check the
      progress of the disease, and even at the time when jaundice had already appeared,
      the injection of 0.1 to 1 cc. saved three out of four animals inoculated with
      Strain 3 and one out of three inoculated with Strain 1. The native guinea pigs
      secured in Payta proved to be unusually refractory to infection with Leptospira
      icteroides as compared with normal guinea pigs recently imported from New York.
      Fresh rabbit serum is recommended for culture work with Leptospira icteroides.

PMID- 19868494
TI  - MIGRATION OF LYMPHOCYTES IN PLASMA CULTURES OF HUMAN LYMPH NODES.
AB  - 1. Lymphocytes were usually the first cells to migrate out into the plasmic clot
      from explanted pieces of lymph nodes. 2. Their paths of migration were irregular
      but in general they proceeded away from the explant. 3. The lymphocytes migrated
      at rates varying from 0.03 to 0.0013 mm. per minute. The rate of any one varied
      from minute to minute, and they often came to rest for varying lengths of time.
      4. The migrating lymphocytes were very much elongated, with the nucleus always
      near the anterior end. The elongated tail contained the endoplasm with a few
      granular mitochondria and usually a few granules which took up neutral red. 5.
      The lymphocytes in cultures made from normal and pathological lymph nodes in auto
      and homoplasma showed no differences.

PMID- 19868495
TI  - STUDIES ON ENDOTHELIAL REACTIONS : IV. THE ENDOTHELIUM IN EXPERIMENTAL GENERAL
      MILIARY TUBERCULOSIS IN RABBITS.
AB  - 1. Lymphocytes were usually the first cells to migrate out into the plasmic clot
      from explanted pieces of lymph nodes. 2. Their paths of migration were irregular
      but in general they proceeded away from the explant. 3. The lymphocytes migrated
      at rates varying from 0.03 to 0.0013 mm. per minute. The rate of any one varied
      from minute to minute, and they often came to rest for varying lengths of time.
      4. The migrating lymphocytes were very much elongated, with the nucleus always
      near the anterior end. The elongated tail contained the endoplasm with a few
      granular mitochondria and usually a few granules which took up neutral red. 5.
      The lymphocytes in cultures made from normal and pathological lymph nodes in auto
      and homoplasma showed no differences.

PMID- 19868496
TI  - CONDITION OF THE CAPILLARIES IN HISTAMINE SHOCK.
AB  - 1. Histamine exerts a local dilator effect upon capillaries and upon the smallest
      arterioles and venules which border the capillary system. There occurs also an
      opening up of large numbers of capillaries of which no trace can be seen before
      the application of histamine. 2. When injected intravenously in amounts
      sufficient to produce shock, histamine causes a quickly progressive dilatation of
      both the visible and the occult capillaries and of their immediately adjacent
      arterioles and venules, all of which become engorged with blood that moves
      through them in a strikingly sluggish manner. The circulatory failure which
      characterizes histamine shock results from the dilatation of the peripheral
      vascular bed.

PMID- 19868497
TI  - STUDIES ON X-RAY EFFECTS : VI. EFFECT OF THE CELLULAR REACTION INDUCED BY X-RAYS
      ON CANCER GRAFTS.
AB  - Small areas of the skin in the groin of mice were subjected to an erythema dose
      of x-rays and a week later a cancer graft was inoculated intracutaneously into
      the area and at the same time a like graft was inoculated in the same manner in
      the opposite groin protected from x-rays. The graft in the x-rayed area showed a
      low percentage of takes, while that in the normal skin gave the usual high
      percentage When the graft was introduced into the subcutaneous tissues it grew
      equally as well in the x-rayed area as in the protected area. Histological
      examination shows the skin layers, a few days after x-ray treatment, to be
      markedly infiltrated with round cells of the lymphoid type. The reaction did not
      extend deeper than the skin layers. It is suggested that this local lymphoid
      reaction induced by the x-rays controls the graft made into the skin, while its
      absence in deeper tissues accounts for the growth of the grafts more deeply
      implanted.

PMID- 19868498
TI  - EFFECT OF INDUCED CELLULAR REACTION ON THE FATE OF CANCER GRAFTS : IV. STUDIES ON
      LYMPHOID ACTIVITY.
AB  - Mice sensitized by an injection of 0.2 cc. of rat blood and 10 days later
      inoculated with a mixture of rat blood and a transplantable mouse cancer showed a
      high degree of immunity to the cancer growth, while mice sensitized in the same
      manner and inoculated with cancer graft with no rat blood showed no immunity.
      Likewise, non-sensitized mice inoculated with a mixture of rat blood and cancer
      cells showed no immunity. Mice sensitized to rat blood and then given a series of
      doses of x-rays between the time of this injection and the inoculation of the
      cancer-rat blood mixture showed a suppression of the factors affording protection
      or immunity, since the cancers grew as well in these animals as in the controls.
      Mice were sensitized with rat blood and 10 days later inoculated with a cancer
      rat blood mixture. 20 hours after the inoculation when the cellular exudation was
      at its height, the cells were destroyed by a local dose of x-rays. The degree of
      immunity was reduced and the cancers grew almost as well as in the controls.

PMID- 19868499
TI  - THE LYMPHOCYTE IN NATURAL AND INDUCED RESISTANCE TO TRANSPLANTED CANCER : VI.
      HISTOLOGICAL COMPARISON OF THE LYMPHOID TISSUE OF NATURALLY IMMUNE AND
      SUSCEPTIBLE MICE.
AB  - The lymphoid organs of mice show definite changes after cancer inoculation. In
      immune mice there is a tendency towards a lymphoid hyperplasia, while in
      susceptible mice more or less marked depletion of the lymphoid tissue takes
      place. These changes are evident at the end of the 3rd week after cancer
      inoculation.

PMID- 19868500
TI  - GENERAL LEUCOCYTIC RESPONSE OF THE GUINEA PIG DURING THE REACTION OF ARTIFICIAL
      IMMUNITY IN EXPERIMENTAL TUBERCULOUS INFECTION.
AB  - Guinea pigs have been rendered relatively immune against infection with virulent
      tubercle bacilli by preliminary inoculation with a suitable quantity of avirulent
      tubercle bacilli. Blood counts on these animals show that associated with the
      immune reaction there is a definite general leucocytic response characterized by
      an absolute increase in the total count, with an absolute and relative increase
      in the lymphocytes. The period of greatest activity coincides with that known to
      be the period of greatest reaction, based on anatomical evidence during the
      course of infection following this method of immunization. Moreover, blood counts
      made on animals inoculated with avirulent tubercle bacilli alone show an increase
      in the circulating lymphocytes during the period of greatest reaction to the
      infection, while blood counts on guinea pigs inoculated with virulent bacilli
      alone show an erratic course in which the polymorphonuclear forms are much
      increased, though not regularly so. These results indicate a parallelism between
      lymphoid activity and resistance of the animals to tuberculous infection, and
      suggest an association of lymphocytes with the factors determining this
      resistance, a relation which warrants consideration of the blood picture in the
      clinical study of tuberculous infection.

PMID- 19868501
TI  - GIANT CELLS IN CULTURES FROM HUMAN LYMPH NODES.
AB  - Giant cells resembling those found in tuberculous nodes appeared in cultures of
      various normal and pathological human lymph nodes cultivated in plasma. They
      migrated out from the explants from normal and tuberculous nodes, from nodes from
      acute and chronic lymphadenitis and Hodgkin's disease, and from a metastatic
      sarcoma. They were most abundant in cultures from tuberculous nodes. The giant
      cells are similar in structure to the large wandering cells and probably arise
      from them. We are uncertain, however, as to how the giant cells develop. There is
      no evidence of fusion of the large mononuclear wandering cells; on the other
      hand, there is some evidence that they arise by amitosis of the nuclei without
      division of the cytoplasm, which increases in bulk. They contain a large central
      area of more or less granular character which takes up neutral red with great
      avidity. This central area probably consists of dead material, the waste products
      of metabolism and of digested foodstuffs such as lymphocytes that the cells are
      unable to get rid of in the abnormal environment, and perhaps also of accumulated
      non-living foreign substances that have penetrated into the cells and become
      segregated. The central area is surrounded by a conspicuous zone of fat globules
      in which the nuclei are embedded. The nuclei vary in number from 2 or 3 to 50 or
      60. Usually, however, there are not more than 10 or 20, and in the cells that are
      flattened out on the cover-slip they often have a horseshoe-like arrangement
      about the equator of the central area. Mitochondria are abundant and usually in
      the form of wavy or curly threads. They seem to be most numerous in the ectoplasm
      immediately about the fat zone. They also extend in among the fat globules and
      out into the ectoplasm. A distinct, clear, homogeneous ectoplasm envelops the
      cell.

PMID- 19868502
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      II. FILTERABILITY AND RESISTANCE TO GLYCEROL.
AB  - All active transmissible agent present in the nasopharynx in early cases of
      influenza has been found to produce definite and characteristic clinical
      reactions and pathological effects in rabbits as already described in an earlier
      publication. The experiments here reported indicate that this active agent has
      the following properties. 1. The agent as it exists in the nasopharyngeal
      secretions in man, and in the lungs of rabbits injected with the human
      secretions, passes through Berkefeld V and N candles. 2. The filtered material
      produces the same effects on the circulating blood and on the lungs of rabbits as
      the unfiltered material. 3. The peculiar effects described as arising in the
      inoculated rabbit may also be induced in guinea pigs inoculated with the agent.
      4. The agent responsible for the reaction on the blood and the lungs of rabbits
      withstands the action of glycerol in a sterile 50 per cent solution, for periods
      up to 9 months. The question must be left open at present whether the agent can
      withstand longer contact with the chemical. In two experiments after 10(1/2)
      months contact the agent induced no observable changes in the blood and lungs of
      rabbits.

PMID- 19868503
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      III. STUDIES OF THE CONCURRENT INFECTIONS.
AB  - 1. Concurrent infections in the experiments described may be regarded as of
      accidental nature and are not causally related to the typical effects induced in
      rabbits by a material wholly free from ordinary bacteria. 2. The influenzal agent
      exerts an effect on the pulmonary tissue which encourages the invasion of the
      lung and subsequent multiplication there of ordinary bacteria, such as the
      pneumococcus, streptococcus, and Bacillus pfeifferi. 3. A similarity is believed
      to exist between the conditions under which concurrent infections arose in the
      inoculated rabbits and those which seem to favor the occurrence of concurrent
      infections during epidemic influenza in man. In no instance did death occur in
      the rabbits as a result of the uncomplicated effects of the influenzal agent
      alone. When death occurred in any of the inoculated animals concurrent infection
      of the lungs by ordinary bacteria was present. The microorganisms most commonly
      met with under these conditions were Pneumococcus Type IV and atypical Type II,
      streptococci, and hemoglobinophilic bacilli. Other kinds were encountered less
      often.

PMID- 19868504
TI  - STUDIES ON MEASLES : I. SUSCEPTIBILITY OF MONKEYS TO THE VIRUS OF MEASLES.
AB  - By the intratracheal injection into monkeys of unfiltered nasopharyngeal washings
      from cases of measles in the preeruptive and early eruptive stages of the disease
      a relatively constant group of symptoms was induced which closely resemble those
      of measles in man. Of seven monkeys inoculated intratracheally with unfiltered
      nasopharyngeal washings from seven cases of measles, five developed the symptoms.
      The same group of symptoms was induced in one monkey by inoculation of the mucous
      membrane of the nose and mouth with unfiltered nasopharyngeal washings from a
      case of measles. In these experiments a variety of organisms, largely saprophytic
      inhabitants of the nasopharynx and mouth, were present in the material
      inoculated. There is sufficient evidence, however, that these organisms were in
      no way responsible for the reaction, since the same group of symptoms was induced
      in two monkeys by the intratracheal injection of nasopharyngeal washings from
      three cases of measles after the washings had been freed from ordinary organisms
      of the mouth flora by filtration through Berkefeld N filters. The characteristic
      group of symptoms which follows the inoculation of monkeys with the
      nasopharyngeal washings from patients with measles has been. successfully carried
      through six passages by intratracheal injection of saline emulsions of the skin
      and buccal mucous membranes of monkeys killed from 2 to 6 days after the onset of
      the reaction. From the fourth passage monkey the reaction was also successfully
      induced in three monkeys by means of citrated whole blood injected intravenously.
      This experiment showed the blood to be capable of inciting the reaction from at
      least the 7th to 13th days after intratracheal inoculation of the donor monkey,
      but incapable of inducing it from the 2nd to 4th days. Cultures of the blood
      showed no growth. The group of symptoms induced has been constant and definite in
      character. After an incubation period of 6 to 10 days the animal becomes listless
      and drowsy, the conjunctivae become injected, and small, discrete, hyperemic
      macules appear on the labial mucous membrane. These spots increase in number and
      may eventually coalesce in the course of 2 to 4 days to form a diffuse, red,
      granular rash. This rash is usually limited to the labial mucous membrane but may
      extend to the inside of the cheeks. The individual macules may or may not show
      the minute bluish white center characteristic of Koplik spots. From one to
      several days after onset an eruption of small, discrete, red maculopapules
      appears on the skin, usually coming out first on the face. The rash progressively
      increases in the number and size of the individual lesions and may in the course
      of 2 to 3 days extend to the skin of the neck, shoulders, upper arms, chest,
      abdomen, and thighs. It is constant in character but varies considerably in
      extent in different animals. By the time the exanthem is fully developed, the
      rash on the mucous membranes has begun to fade and soon disappears. The exanthem
      in turn progressively fades, sometimes with a branny desquamation, sometimes
      without. There may be moderate pigmentation. By the 6th to the 10th day after
      onset all symptoms have disappeared and the animal again appears well. Coincident
      with this group of symptoms there is a constant and definite reduction in the
      total leucocyte count, frequently constituting a true leucopenia. Other symptoms
      of irregular occurrence are photophobia, diarrhea, and fever. Symptoms of
      rhinitis and bronchitis have not been noted. Histological sections of the lesions
      of the skin show an exudative and proliferative lesion about the capillaries of
      the corium in which endothelial leucocytes are the predominating cells. Mitotic
      cells are not infrequently present in these areas. The endothelial leucocytes may
      be seen migrating toward and occasionally invading the epithelial layers of the
      hair follicles, sebaceous glands, and epidermis. In places the epithelial cells
      appear edematous and vacuolated, and there is evidence of minute vesicle
      formation. The lesions of the labial mucous membrane are similar in character.
      Minute vesicle formation in the epithelium is more frequent and the vesicles
      occasionally assume a more pustular appearance. Similar lesions are found in
      histological sections of the tongue. Cultures of the blood made both during the
      incubation period and during the course of the reaction in a variety of media,
      aerobic and anaerobic, have consistently shown no growth. The close similarity of
      the symptoms and pathological lesions of the reaction to the symptoms and
      pathological lesions of measles, the successful transmission of the reaction from
      monkey to monkey, and the elimination of ordinary bacteria as a possible source
      of error in the interpretation of the results, warrant the belief that the
      reaction is caused by the inciting organism of measles.

PMID- 19868505
TI  - STUDIES ON MEASLES : II. SYMPTOMATOLOGY AND PATHOLOGY IN MONKEYS EXPERIMENTALLY
      INFECTED.
AB  - The symptomatology of the reaction induced in monkeys by inoculation with
      material containing the virus of measles is described. The symptoms and course of
      this reaction closely parallel those of human measles. The microscopic pathology
      of the lesions of the skin and buccal mucous membrane of monkeys experimentally
      infected with the virus of measles is also described. These lesions are
      essentially identical with the corresponding lesions of measles in man.

PMID- 19868506
TI  - STUDIES ON LYMPHOID ACTIVITY : V. RELATION BETWEEN THE TIME AND EXTENT OF
      LYMPHOID STIMULATION INDUCED BY PHYSICAL AGENTS AND THE DEGREE OF RESISTANCE TO
      CANCER IN MICE.
AB  - It has been shown that resistance to transplanted cancer follows stimulation of
      the lymphoid tissue when the stimulation is induced by either heat or small doses
      of x-rays. In this paper we have attempted to determine whether the degree of
      immunity had a quantitative relation to the amount of the stimulation.
      Fortunately, the two methods at our disposal give stimulation of markedly
      different characters. The small dose of x-rays gives a sluggish lymphoid cell
      reaction of short duration with a definite latent period between the treatment
      and the evidence of marked stimulation, while after heat a short period of
      depression is followed by a sharp stimulation continuing over a much longer
      period. The cancer inoculation into groups of mice made immediately after
      exposure to x-rays shows little resistance, while the inoculation made at the
      height of the stimulation phase shows a definite increase in the immunity.
      Animals inoculated with cancer immediately after the heat treatment exhibit a
      pronounced immunity, but not so marked as that shown when the inoculation is made
      at the height of the stimulation. The amount of resistance shown when the cancer
      inoculation is made at the height of the moderately stimulating effect following
      exposure to x-rays, is much less than that seen when the inoculation is made at
      the height of the heat effect when the degree of stimulation is much greater.
      When the lymphocytosis sets in after the tumor graft is established only a slight
      effect is noted. All these results together are taken to indicate that the degree
      of immunity is dependent on the amount of lymphoid stimulation existing either at
      the time of or following soon after the cancer inoculation.

PMID- 19868507
TI  - STUDIES ON X-RAY EFFECTS : VII. EFFECT OF SMALL DOSES OF X-RAYS OF LOW
      PENETRATION ON THE RESISTANCE OF MICE TO TRANSPLANTED CANCER.
AB  - A relatively increased degree of resistance in mice to a certain strain of
      transplantable cancer was demonstrated after treatment of animals with small
      doses of x-rays capable of stimulating lymphoid tissue. The refractory state
      induced was determinable 3 to 7 days after the dose of x-rays was given.

PMID- 19868508
TI  - STUDIES ON X-RAY EFFECTS : VIII. INFLUENCE OF CANCER INOCULATION ON THE LYMPHOID
      STIMULATION INDUCED BY SMALL DOSES OF X-RAYS.
AB  - Mice treated with small doses of x-rays and inoculated with cancer immediately
      afterwards, show a marked suppression of lymphoid proliferation. If, however, the
      cancer inoculation is made 7 days after the exposure to x-rays, thus permitting
      the primary lymphoid stimulation known to occur soon after the x-ray treatment to
      arise, a second stimulation takes place in a large proportion of mice thus
      inoculated. Changes in the blood of mice x-rayed and inoculated with cancer 7
      days afterwards show that the state of resistance to cancer inoculation is
      attended by blood lymphocytosis, as is the case in all other varieties of
      immunity to transplanted cancer so far studied.

PMID- 19868509
TI  - THE ETIOLOGICAL RELATION OF BACILLUS ACTINOIDES TO BRONCHOPNEUMONIA IN CALVES.
AB  - A bronchopneumonia of calves in the early months of life is described and its
      etiology associated definitely with a minute bacillus, Bacillus actinoides.
      Bacillus pyogenes, Bacillus bovisepticus, and, less frequently, staphylococci and
      streptococci may appear later in the affected lungs. Subcutaneous injections of
      cultures of Bacillus actinoides produce large indurations ending in necrosis.
      Similarly intratracheal injections produce circumscribed necroses of lung tissue.
      The cultivation of Bacillus actinoides and its morphological peculiarities have
      been sufficiently described and illustrated in an earlier publication to ensure
      success on the part of those who attempt to isolate it.

PMID- 19868510
TI  - PRECIPITIN RESPONSE IN THE BLOOD OF RABBITS FOLLOWING SUBARACHNOID INJECTIONS OF
      HORSE SERUM.
AB  - 1. Rabbits which have received a single dose of normal horse serum in the
      subarachnoid space produce precipitins in the blood in greater abundance, of
      higher titer, and persisting longer than those in control rabbits which have
      received a similar injection intravenously. 2. Repeated subarachnoid injections
      of normal horse serum in rabbits induce precipitins in the blood early. These may
      appear in high titer as soon as 1 week after the initial injection, whereas in
      rabbits similarly treated intravenously no precipitins are found at this time.
      They may appear a few days afterward and reach a high titer. 3. No anaphylactic
      manifestations occurred in rabbits treated repeatedly with subarachnoid
      injections of normal horse serum when the precipitin content of the blood was
      high. 4. Anaphylactins, as determined by passive transfer of anaphylaxis, were
      demonstrated in sera with high precipitin content. 5. These experiments may
      explain clinical evidences of anaphylaxis, observed when an initial intravenous
      injection of horse serum followed a series of intraspinal injections of such
      serum.

PMID- 19868511
TI  - GRANULES IN THE CELLS OF CHICK EMBRYOS PRODUCED BY EGG ALBUMIN IN THE MEDIUM OF
      TISSUE CULTURES.
AB  - It is difficult to understand what factors may be concerned in the formation of
      the al. granules. The phenomenon may be concerned with changes in the cell
      membrane due to an abnormal environment; that is, material which would otherwise
      be excluded may be permitted to enter the cell, or, on the other hand, certain
      substances may be prevented from passing out of the cells. Previous investigators
      have shown that mesenchyme cells sometimes engulf certain foreign bodies, and it
      is possible that the solution of white of egg is ingested in the same manner.
      When a solution of peptone was placed on the cells instead of egg white, the
      phenomenon did not occur (Fig. 13); the cell remained normal and degenerated in
      the usual manner (Fig. 14). This would seem to indicate that the al. granules are
      not formed from peptone. Regardless of the factors involved, it is evident that
      egg albumin in the medium of tissue cultures of chick embryos causes the
      formation of numerous large granules in the cytoplasm of the connective tissue
      cells. This phenomenon is associated with unfavorable conditions for the life of
      the cells and results in the rapid death of the cultures.

PMID- 19868512
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : VI. AFFECTIONS OF BONE, CARTILAGE, TENDONS,
      AND SYNOVIAL MEMBRANES. PART 1. LESIONS OF THE SKELETAL SYSTEM.
AB  - From a study of a series of rabbits inoculated with two old strains of Treponema
      pallidum, it was found that localized infection of bones and tendons was of
      frequent occurrence and led to the formation of a variety of lesions. The bones
      usually involved were those of the face and the feet and legs. Most often the
      lesions arose from the periosteum but developed also within the bone or marrow
      cavities and at lines of epiphyseal union. Grossly, the periosteal lesions were
      of two types-one being a circumscribed, indurated, and nodular mass and the other
      a process of a more diffuse character. Histologically, the lesions presented the
      typical appearance of syphilitic granulomata composed of more or less distinct
      layers which corresponded roughly with structural divisions of the periosteum.
      The composition of lesions of membrane and of cartilage bones differed somewhat
      in this respect, especially in the development of an osteoclastic layer. Invasion
      of the bone with absorption and necrosis were constant features of periosteal
      affections and were most marked in the case of the facial bones and the small
      bones of the feet. Lesions in the bone and marrow cavities were detected chiefly
      by radiographs or by the occurrence of bone destruction in the absence of
      periosteal involvement. They were characterized by a loss of structural detail in
      the bone, rarefication, increased fragility, necrosis, pathological fracture, and
      epiphyseal separation associated with more or less granulomatous reaction.
      Histologically, the bone lesions presented essentially the same picture as those
      of the periosteum, while the lesions which arose from the marrow cavities were
      composed chiefly of polyblastic infiltrations. In this group of affections, the
      most important were those which developed at the epiphyses. The destructive
      effects produced by all classes of lesions varied from a slight surface erosion
      or rarefication to extensive necrosis resulting in the formation of bony defects
      or in disintegration or fracture of the bone. These conditions differed very
      decidedly with the particular bones involved. Of especial importance in this
      connection was the occurrence of a peculiar form of mass necrosis which at times
      resulted in the destruction of considerable areas of bone even in parts where the
      granulomatous type of lesion was comparatively slight. The most characteristic
      injuries were the saddle-nose deformities and the epiphyseal separation in the
      small bones of the tarsus and hind feet. The marks of permanent injury were, on
      the whole, comparatively slight, but they also differed both with the degree of
      the original injury and with the bone affected. Granulomatous lesions of tendons
      or tendon sheaths were occasionally seen, and in a few instances, lesions of
      synovial cavities were demonstrated microscopically.

PMID- 19868513
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : VI. AFFECTIONS OF BONE, CARTILAGE, TENDONS,
      AND SYNOVIAL MEMBRANES. PART 2. CLINICAL ASPECTS OF SYPHILIS OF THE SKELETAL
      SYSTEM. AFFECTIONS OF THE FACIAL AND CRANIAL BONES AND THE BONES OF THE FOREARM.

PMID- 19868514
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : VI. AFFECTIONS OF BONE, CARTILAGE, TENDONS,
      AND SYNOVIAL MEMBRANES. PART 3. SYPHILIS OF THE POSTERIOR EXTREMITIES WITH OTHER
      AFFECTIONS OF A MISCELLANEOUS TYPE.
AB  - A systematic study was made of the affections of bone, cartilage, tendons, and
      synovial membranes which occurred in a series of rabbits with generalized
      syphilis. Localized infection of this group of structures was found to be of very
      frequent occurrence. The parts involved were, in the order of their frequency,
      the facial and cranial bones and cartilages, the bones, tendons, and joints of
      the feet and legs, the cervical and caudal vertebrae, the ribs, and the sternum.
      These infections often gave rise to characteristic manifestations of disease
      which could be detected without difficulty by inspection or palpation of the
      part. In many instances, however, clinical manifestations were so slight that the
      presence of lesions could be detected only by radiographic or pathological
      examination. Detailed descriptions of various clinical types of disease were
      given and the clinical manifestations correlated with the pathological process.
      It was pointed out that bone lesions exhibited a decided predilection for certain
      exposed bony prominences, for lines of bony union, and for epiphyseal lines in
      particular. A study of the clinical history of bone lesions brought out the fact
      that they were among the earliest of the generalized forms of disease; they
      tended to pursue a comparatively rapid course, and relapse was never observed.
      Especial emphasis was laid upon three aspects of the experimental infection: the
      analogy existing between certain forms of the animal and human affections, the
      relation of syphilis of the osseous system to other evidences of disease, and the
      occurrence of obscure bone lesions. In this connection, it was pointed out that
      the nasal and epiphyseal lesions of the rabbit presented a striking analogy to
      those of congenital syphilis in man. It was also pointed out that syphilis of the
      osseous system occupied a definite position in the scheme of defensive reactions
      such that lesions of these tissues might be favored or inhibited according to the
      experimental conditions employed. Finally, the frequency with which infections
      occurred which were not accompanied by sufficiently distinctive signs even to
      suggest the possibility of their existence was interpreted as evidence that some
      cases of latent or obscure infection in man might find their explanation in the
      presence of a similar group of affections.

PMID- 19868515
TI  - A NEW STRAIN OF TRANSMISSIBLE LEUCEMIA IN FOWLS (STRAIN H).
AB  - 1. A new strain of fowl leucosis has been transmitted through twelve generations
      of fowls. 2. An increase in virulence was observed during its passage. This was
      shown in a shortening of the interval between inoculation and death. The increase
      in virulence does not affect the number of successful inoculations, which remains
      approximately constant in from 20 to 40 per cent of the birds employed. 3. As
      with former strains, the disease manifests itself in various forms; i.e., myeloid
      and intravascular lymphoid types. A single lymphatic case was observed. 4. In
      several intravascular cases a diminution in the hemolytic power of the serum was
      established. This phenomenon was absent in a number of myeloid cases. 5. Active
      immunization cannot be produced by means of the subcutaneous injection of
      virulent material. 6. The finding of previous experiments that the virus is
      filterable has been confirmed. 7. The inoculation of human leucemic material into
      fowls gave negative results.

PMID- 19868516
TI  - SUPERINFECTION IN EXPERIMENTAL SYPHILIS FOLLOWING THE ADMINISTRATION OF
      SUBCURATIVE DOSES OF ARSPHENAMINE OR NEOARSPHENAMINE.
AB  - Experiments were carried out on rabbits for the purpose of determining the
      effects of subcurative doses of arsphenamine and of neo-arsphenamine upon the
      resistance of infected animals to reinoculation with Treponema pallidum and hence
      the possibilities of the occurrence of a second infection in treated but uncured
      cases of infection. All the animals used were inoculated with the same virus, and
      the experimental tests were carried out when the first cycle of testicular
      reaction was nearing its height. The animals with the most marked testicular
      lesions were used for the basic experiment of treatment and reinoculation. The
      results of this experiment were controlled from four different standpoints: (1)
      the effect of the treatment employed upon the existing infection; (2) the
      immunity present at the time of treatment; (3) the virulence of the organisms
      used for reinoculation as compared with those causing the existing infection; (4)
      the comparative susceptibility of normal animals to the virus used for
      reinoculation. The results obtained showed (1) that the treatment employed was
      insufficient to cure any of the therapeutic controls; (2) that the infected
      controls were highly refractory to a second inoculation; (3) that the treated
      animals were highly susceptible to a second inoculation and although not cured of
      their original infection, reacted to the second inoculation with the formation of
      lesions indistinguishable from those of a first infection; (4) that in certain
      instances the treatment given had rendered infected animals more susceptible to
      infection than the normal controls.

PMID- 19868517
TI  - FURTHER STUDIES ON THE BEHAVIOR OF BACTERIA TOWARD GENTIAN VIOLET.
AB  - 1. A gentian-positive strain (a "strain-within-a-strain" variant) has been
      isolated from a pure culture of a gentian-negative organism. This observation
      corresponds to that of a "strain-within-a-species" variant, occurring in the
      enteritidis group, reported some years ago. 2. The Gram reaction and the gentian
      reaction do not depend, as has been assumed in previous publications, on the
      specific affinity of the gentian-positive organisms for a portion of the gentian
      violet molecule, since certain Gram-negative strains are shown to be gentian
      positive. 3. Dead bacterial bodies interposed between living bacteria and gentian
      violet media partially negative the effect of the dye on Gram-positive organisms
      and allow them to grow. This seems to be either a phenomenon of filtration or of
      stimulation of growth. 4. The application of these facts by the method of divided
      plates shows a number of difficulties in the application of laboratory studies to
      chemotherapeutics, which would escape observation by ordinary methods.

PMID- 19868518
TI  - COMMUNAL ACTIVITY OF BACTERIA.
AB  - 1. The behavior of a single bacterial cell toward gentian violet differs
      fundamentally from that of a small group of cells (thirty). 2. The explanation of
      this phenomenon is not purely quantitative; thirty cells accomplish much more
      than thirty times what one cell can accomplish.

PMID- 19868519
TI  - FATE OF THE LYMPHOCYTE.
AB  - Although the count of circulating lymphocytes in the blood stream remains
      constant, more lymphocytes enter the blood from the thoracic duct during 24 hours
      than are present in the blood at any one time. This excess of lymphocytes is not
      destroyed in the blood stream. The cells migrate from the blood vessels into the
      mucous membranes and through them to their surface. This occurs chiefly in the
      gastrointestinal tract, and it is apparently in the mucosa and especially within
      the intestinal lumen that the function of the lymphocyte is normally performed.

PMID- 19868520
TI  - RELATION OF ANTIBODY AND ANTIGEN TO SERUM DISEASE SUSCEPTIBILITY.
AB  - 1. Studies on nineteen patients to whom foreign serum had been administered for
      therapeutic purposes are reported. Analysis of the results obtained by following
      the precipitin and precipitinogen in the circulation and comparing these factors
      with the time of appearance, intensity, and duration of the symptoms shows that
      the nineteen patients fall into three groups. 2. The first group includes eleven
      patients. These were good precipitin formers, they had severe serum disease, and
      the precipitinogen disappeared from the circulation near the time that the
      symptoms subsided. 3. The second group includes four patients who had little or
      no serum disease, in whose circulation little or no precipitin was demonstrable,
      and in whom the precipitinogen persisted in the circulation as long as the
      patients could be kept under observation-from 52 to 67 days. 4. The remaining
      four patients form a more or less distinctly intermediate group. 5. The results
      lend further support to the conception of serum disease as an antigen-antibody
      reaction. 6. The possibility that our results indicate a factor which may be
      important in the mechanism of natural immunity is discussed.

PMID- 19868521
TI  - STUDIES ON MEASLES : III. ACQUIRED IMMUNITY FOLLOWING EXPERIMENTAL MEASLES.
AB  - It is shown that monkeys which have recovered from experimental measles are
      immune to reinfection with the virus of measles irrespective of whether the virus
      is of homologous or heterologous origin. In this respect experimental measles in
      the monkey corresponds with measles as observed in human beings, and the result
      is the same whether the virus is inoculated on the respiratory mucous membrane or
      is injected intravenously.

PMID- 19868522
TI  - STUDIES ON BLOOD CHANGES IN PNEUMOCOCCUS INFECTIONS : AN EXPERMENTAL STUDY OF THE
      FORMATION AND FATE OF METHEMOGLOBIN IN THE BLOOD.
AB  - In the occasional cases of pneumonia which show a decrease in the oxygen capacity
      of the blood, the decrease is probably due to a formation of methemoglobin. The
      latter is removed from the circulation, however, as rapidly as it is formed, so
      that it can seldom be detected even qualitatively, and is probably never a cause
      of cyanosis.

PMID- 19868523
TI  - FIBRIN AND SERUM AS A CULTURE MEDIUM.
AB  - A technique is described by which a medium composed of fibrinogen suspension,
      serum, and embryo juice may be made. Fibroblasts grew in this medium about as
      well as in plasma and embryo juice. A strain of connective tissue in this medium
      remained practically as active as the control for several passages.

PMID- 19868524
TI  - FLAGELLUM OF THE MICROORGANISM OF RAT-BITE FEVER.
AB  - The work of previous investigators was confirmed in that the microorganism of rat
      bite fever was found to have flagella which are clearly visible by dark-field
      illumination and which can be stained. The best staining is obtained with
      alkalinized Akashi solution, which is a modification of Giemsa's solution; the
      vapor of osmic acid gives the best fixation. The number of demonstrable flagella
      seems to vary with the technique. Sometimes many slender flagella unite into one
      large one or one large flagellum divides into several smaller ones. It may be
      concluded that commonly many slender flagella occur at the ends and that these
      may unite into one or several large flagella. In the living microorganism the
      flagella appear to be spiral. Their form in fixed preparations depends upon the
      method employed. Some long forms have flagella arising at the middle of the body;
      this seems to indicate that division is transverse and not longitudinal as
      generally believed. The rigid body, the signs of transverse division, and
      multiple flagella seem to distinguish the forms reported here from spirochetes
      and indicate that they are spirilla.

PMID- 19868525
TI  - IMMUNOLOGIC STUDY OF STRAINS OF BACILLUS PFEIFFERI ISOLATED FROM A CASE OF
      MENINGITIS.
AB  - Five strains of Bacillus pfeifferi were isolated from a case of meningitis. These
      strains came from the spinal fluid, blood, nose, throat, and nasopharynx.
      Immunologic reactions show no definite relations between these strains, although
      those from the nose, throat, and nasopharynx might be presumed to be related to
      one another. It is also presumable that the spinal fluid strain was derived from
      the upper air passages, and that the blood was invaded from the meninges. In
      spite of immunologic differences, it is believed that the five strains were
      genetically related. The variations in these five strains from a single case are
      as great as those which have been found by others for strains from different
      cases, or individuals. As determined by immunologic reactions, the number of so
      called strains of Bacillus pfeifferi is apparently limited only by the number of
      cultures which have been or might be isolated. It is inconceivable that under the
      designation Bacillus pfeifferi is included a heterogeneous mixture of innumerable
      distinct races of bacteria; there must be some biological relation which cannot
      be established by agglutination, complement fixation, or opsonin reactions. The
      variations which have been noted, may be an indication of a degree of instability
      which may have some bearing upon questions relating to the epidemiology of
      Bacillus pfeifferi infections and to the serum therapy of influenzal meningitis.
      The strain variations which have been shown to exist by immunologic methods do
      not support the theory of the etiological relationn of Bacillus pfeifferi to
      epidemic influenza, unless it can be shown that such variations are due to
      instability of the organism. The fact that the incidence of meningeal involvement
      was only slightly increased during the last pandemic is also evidence against the
      causal relation of the organism to the pandemic disease.

PMID- 19868527
TI  - A USEFUL HEART METHOD.

PMID- 19868526
TI  - THE INCIDENCE OF BLACKHEAD AND OCCURRENCE OF HETERAKIS PAPILLOSA IN A FLOCK OF
      ARTIFICIALLY REARED TURKEYS.
AB  - In a flock of artificially reared turkeys originally consisting of 85 birds and
      reduced during the summer and fall by deaths and withdrawals for experimental
      purposes to 42 birds, five cases of blackhead occurred. These appeared during the
      months of July, September, and October. In four, Heterakis was searched for and
      found. In 38 birds from this flock killed for food during November and December,
      five harbored no Heterakis, and the rest carried light infestations. Of sixteen
      healthy birds withdrawn from the above flock during July and placed with a flock
      of older birds which had passed through this disease in former seasons, all
      contracted blackhead and fourteen died of the disease. The infestation with
      Heterakis was, as a rule, high, reaching a hundred specimens in some cases. In
      general, it appears that a high infestation with Heterakis is correlated with a
      high incidence of blackhead, a relation that had already been inferred in feeding
      experiments. In both of these groups no other species of worm was found in the
      ceca, and in instances in which examinations for coccidia were made none was
      found. Pheasants have been incriminated as a source of infestation with Heterakis
      papillosa in artificially reared flocks. In an artificially reared flock 38 birds
      that had never been ill, when killed in November and December, failed to show
      lesions of blackhead or evidence in the nature of scars that they had passed
      through an attack of the disease. Infectious soil that had remained unoccupied by
      turkeys and chickens for a period of 5 months beginning in the depth of a severe
      winter still harbored viable ova of Heterakis and proved highly dangerous to
      young poults. These experiments and observations fail to throw any light on the
      source of the protozoan parasite (Amoeba meleagridis) which causes the fatal
      lesions of blackhead.

PMID- 19868528
TI  - AN IMPROVED ANAEROBE JAR.
AB  - There has been described a modification of the anaerobe jars of McIntosh and
      Fildes and of Smillie in which the oxygen is consumed by combustion with hydrogen
      under the catalytic action of platinized or palladinized asbestos. The special
      advantages of the apparatus described reside in its greater safety and in the
      fact that the catalyzer is heated electrically after the jar is closed and may be
      reheated at any time during incubation without opening the jar.

PMID- 19868529
TI  - ETIOLOGY OF YELLOW FEVER : XIII. BEHAVIOR OF THE HEART IN THE EXPERIMENTAL
      INFECTION OF GUINEA PIGS AND MONKEYS WITH LEPTOSPIRA ICTEROIDES AND LEPTOSPIRA
      ICTEROHAEMORRHAGIAE.
AB  - 1. Slowing of the heart occurred in monkeys and guinea pigs during the febrile
      period of the experimental infection due to Leptospira icteroides. A similar
      reaction took place in animals inoculated with Leptospira icterohoemorrhagioe. 2.
      The mechanism of slowing was usually due to slowing of the whole heart. 3. Once
      incomplete heart block was seen. Changes in the ventricular complex occurred four
      times.

PMID- 19868530
TI  - CHEMOTHERAPEUTIC STUDIES WITH ETHYLHYDROCUPREINE HYDROCHLORIDE IN EXPERIMENTAL
      PNEUMOCOCCUS PLEURITIS.
AB  - 1. Solutions of ethylhydrocupreine (optochin) hydrochloride show a pronounced
      bactericidal activity for pneumococci in pleural pus. 2. The highest tolerated
      dose of ethylhydrocupreine hydrochloride for guinea pigs by intrapleural
      injection is about 0.2 to 0.3 cc. of a 1:100 solution per 100 gm. of weight,
      corresponding to 2 to 3 cc. of solution or 0.02 to 0.03 gm. of the drug per kilo
      of weight. 3. The injection of 1 cc. of a 1:500 solution of ethylhydrocupreine
      hydrochloride into each pleural cavity of a guinea pig weighing from 350 to 500
      gm. produces no evidences of toxicity or irritation of the pleura. 4. The
      injection of 1 cc. of a 24 hour dextrose blood broth culture of virulent Type I
      pneumococci into the right pleural cavity of guinea pigs produces acute
      suppurative pleuritis on both sides associated with suppurative pericarditis,
      which generally terminates fatally within 72 hours with pneumococcus bacteremia.
      5. The injection of 1 cc. of 1:500 solutions of ethlylhydrocupreine hydrochloride
      into each pleural cavity of guinea pigs at varying intervals up to 24 hours after
      pleural infection has usually shown a marked curative influence. Similar results
      were observed with dogs. 6. The intrapleural injection of mixtures of
      ethylhydrocupreine, sodium oleate, and boric acid (Lamar) has also shown a
      decided curative effect in acute suppurative pneumococcus pleuritis of guinea
      pigs. 7. These and similar experiments on pneumococcus meningitis suggest that in
      chemotherapeutic investigations certain drugs may be injected into serous
      cavities in amounts exerting distinct bactericidal activity in vivo without
      producing local irritation or general toxic effects.

PMID- 19868531
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      IV. ANAEROBIC CULTIVATION.
AB  - From the filtered nasopharyngeal washings of patients in the first 36 hours of
      uncomplicated epidemic influenza and rarely in later stages of the disease, we
      have cultivated a minute bacilloid body, Bacterium pneumosintes, 0.15 to 0.3
      microns in length, of constant cultural characters and capable of indefinite
      propagation on artificial media. This organism, not of the nature of ordinary
      bacteria, was also recovered in pure culture from the unfiltered and filtered
      lung tissue of rabbits and guinea pigs inoculated with unfiltered and filtered
      nasopharyngeal washings of early influenza cases, both from the first epidemic of
      1918-19 and from the second one of 1920. The organism grows only under strictly
      anaerobic conditions, passes Berkefeld V and N filters, and withstands the action
      of sterile 50 percent glycerol for a period of months. It has been recovered from
      cultures contaminated with a variety of ordinary bacteria such as Bacillus
      pfeifferi, pneumococci, streptococci, and staphylococci, and has been
      experimentally cultivated in symbiosis with them. Similar cultivation of control
      materials uniformly failed to yield growths of this organism. The materials
      tested consisted of the unfiltered and filtered nasopharyngeal washings of
      persons free from influenza, some of whom were suffering from acute coryza, the
      lung tissue of normal rabbits and of rabbits with bacterial respiratory
      infections, and the uninoculated media. The intratracheal injection in rabbits
      and guinea pigs of mass cultures of this organism has induced effects on the
      blood and lungs of these animals which are not to be distinguished from those
      obtained with the nasopharyngeal secretions of patients in the early hours of
      epidemic influenza. From the pulmonary lesions thus induced the same organism has
      been recovered in pure culture, and has been found to cause similar lesions on
      subsequent animal passage. Its pathogenicity is not lost by prolonged artificial
      cultivation. Our experiments indicate that the cultivable bodies obtained
      directly from human nasopharyngeal washings and from affected rabbit lungs are
      strains of the same organism. This organism appears to be the source of the
      reactions which occur in experimental animals-rabbits and guinea pigs-as a result
      of the intratracheal injection of nasopharyngeal washings obtained during the
      early hours of uncomplicated epidemic influenza in man.

PMID- 19868532
TI  - THE BILIARY OBSTRUCTION REQUIRED TO PRODUCE JAUNDICE.
AB  - The bile ducts from three-quarters of the liver substance in dogs and monkeys can
      be obstructed without any clinical evidence developing of pigment or cholate
      accumulation in the organism. And in the dog nineteen-twentieths of the liver
      substance can be placed in stasis without the occurrence of tissue icterus such
      as regularly follows total obstruction in this animal. There is no reason to
      suppose that this will not be found true in the monkey as well. Always a local
      obstruction results sooner or later in atrophy of the affected tissue with
      compensatory hypertrophy elsewhere. Thus as time passes the derangement of
      function produced by the sudden stasis is progressively lessened. The plasma of
      the dog and monkey, unlike that of man, is normally free from bilirubin, and this
      pigment so readily escapes from the blood into the urine that bilirubinuria is
      often to be found in the dog in the absence of bilirubinemia, while the latter is
      never met with alone in either animal. It follows that in both species the renal
      threshold for bilirubin is much lower than in man,-if indeed one can be said to
      exist at all. The amount of biliary obstruction required to produce jaundice in
      human beings is probably as great as in the experimental animals with which we
      have dealt. The clinical jaundice encountered in association with local liver
      lesions should be viewed not as the result of local bile resorption, but as due
      to a general injury to the hepatic parenchyma or ducts, or to blood destruction.

PMID- 19868533
TI  - TUBERCULIN HYPERSENSITIVENESS IN NON-TUBERCULOUS GUINEA PIGS INDUCED BY
      INJECTIONS OF BACILLUS-FREE FILTRATES.
AB  - 1. When a guinea pig with well developed peritoneal tuberculosis is injected
      intraperitoneally with about 20 cc. of a heavy suspension of a virulent tubercle
      bacillus (Culture H37) death occurs within 24 hours or the animal becomes
      extremely toxic. Such a peritoneal tuberculosis develops in about 1 month after 1
      cc. of. a very heavy suspension of Culture H37 has been introduced into the
      abdominal cavity. If the viscid fluid which is contained within the peritoneal
      cavity is mixed with saline solution and passed through a Berkefeld filter a
      bacillus-free filtrate is obtained which induces in normal guinea pigs a certain
      degree of cutaneous hypersensitiveness to tuberculin. 2. The abdominal organs and
      the parietal peritoneum, to which masses of leucocytes and tubercle bacilli are
      adherent, when crushed and extracted with saline solution yield a filtrate which
      likewise induces a cutaneous hypersensitiveness. 3. The cutaneous
      hypersensitiveness does not appear before the 7th or 8th day after the filtrate
      injection and is therefore considered to be the result of an active sensitization
      of the animal.

PMID- 19868534
TI  - STUDIES ON BACTERIAL NUTRITION : I. GROWTH OF BACILLUS INFLUENZAE IN HEMOGLOBIN
      FREE MEDIA.
AB  - From the data presented in the foregoing experiments it is evident that Bacillus
      influenzae will grow in a fluid medium consisting of plain broth to which have
      been added small amounts of emulsions or extracts of mucoid bacilli or of
      Bacillus proteus. The bacterial extracts may be made by simple boiling of the
      bacillary emulsions in broth or saline solution and centrifuging out the
      bacterial bodies; they may be filtered without losing their growth-inducing
      property. Cultures of Bacillus influenzae in bacterial extract broth, if not too
      small doses of the extracts were employed, always showed heavier growth than the
      control cultures in blood broth, and growth occurred at a considerably earlier
      period than in blood broth. In many instances growth could be seen after 3 to 4
      hours, and a bacterial whirl was always visible after 6 hours incubation. When
      the nature of the culture used for seeding is not stated, this was 0.1 cc. of the
      supernatant fluid of a blood broth culture. All cultures were made in fluid
      medium; solid medium is much more difficult to use in connection with the
      extracts. In explanation of the remarkable growth of Bacillus influenzae in this
      blood-free medium, the idea is proposed that the growth-stimulating effect of the
      bacterial extracts is due possibly to substances of the same nature as the so
      called vitamines. Further investigations on this principle of bacterial nutrition
      will appear in subsequent papers, together with a more thorough study of the
      sources and character of the growth-inducing substances.

PMID- 19868535
TI  - DISSOCIATION OF MICROBIC SPECIES : I. COEXISTENCE OF INDIVIDUALS OF DIFFERENT
      DEGREES OF VIRULENCE IN CULTURES OF THE BACILLUS OF RABBIT SEPTICEMIA.
AB  - Two types of organism have been shown to exist in cultures of the bacillus of
      rabbit septicemia, recently isolated from spontaneous infections. One, Microbe D,
      grows diffusely in serum and plain broth, forms rather opaque, fluorescing
      colonies on serum agar, and is highly virulent for rabbits. These characters are
      retained throughout many passages in serum or plain broth. The other type,
      Microbe G, flocculates rapidly in fluid media, forms translucent) bluish colonies
      with little fluorescence, and exhibits extremely low virulence for rabbits. Like
      Microbe D, its distinguishing characters persist throughout many passages in
      artificial media. Two methods for the dissociation of these varieties from the
      parent culture have been described. The two types are morphologically
      indistinguishable and possess identical fermentation reactions. Rabbits surviving
      inoculation with Type G are resistant to multiple lethal doses of Type D. The
      agglutination reactions bear out this suggestion of the antigenic identity of the
      varieties. Community of antigenic character is rendered certain by the results of
      absorption reactions. Microbe D, in contact with immune serum, flocculates well
      at 55 degrees , but poorly or not at all at 37 degrees C. Microbe G, on the other
      hand, agglutinates easily at both temperatures. Microbe D, after being carried
      through twenty-five passages in serum and in plain broth, retains perfectly its
      characteristics of diffuse growth and of virulence, in the plain as well as in
      the serum broth.

PMID- 19868536
TI  - STUDIES ON DECREASING THE REACTION OF NORMAL SKIN TO DESTRUCTIVE DOSES OF X-RAYS
      BY PHARMACOLOGICAL MEANS AND ON THE MECHANISM INVOLVED.
AB  - When a fixed area of the ears of rabbits is subjected to the action of a standard
      destructive dose of x-rays (30 skin units) the type of reaction resulting depends
      upon the previous treatment of the rabbit. (1) In normal rabbits a mild acute
      inflammation develops in the x-rayed area which leads at once to a perforating
      gangrene within an average of 15 days. (2) If rabbits are x-rayed and about 2
      weeks later injected with horse serum for the first time, a mild acute
      inflammation appears which heals for a time; then a second, subacute inflammation
      sets in which leads to a perforating gangrene. The average time of the process
      from the first inflammation to gangrene is 32 days. (3) If rabbits are sensitized
      with horse serum and 10 days later are exposed locally to the standard dose of x
      rays, the ensuing ear reaction is either similar to the second reaction described
      above, except that it may last up to 110 days, or the first inflammation leads to
      a healing which may be apparently permanent (340 + days). (4) If rabbits are
      first sensitized with horse serum, exposed locally to the standard dose of x-rays
      10 days later, and 13 days after the x-ray treatment reinjected with horse serum,
      the reaction of the x-rayed area of the ears is in general similar to the second
      reaction described above (inflammation-healing-inflammation-gangrene). The
      average time of the whole process is about 42 days. On the basis of the general
      hypothesis that an anaphylactic reaction is initiated in the body when the
      specific antibody meets its antigen, and that both antibody and antigen are
      rendered more or less functionally inert by their interaction, the following
      inferences may be drawn from our experimental results. (1) The protection from
      the effects of a standard destructive dose of x-rays which a previous
      sensitization confers, is referable to the presence of anaphylactic antibodies in
      the x-rayed area. (2) This protection is largely due to the anaphylactic
      antibodies which are anchored in the x-rayed area, and not to those which are
      free in the circulation. (3) An anaphylactic reaction renders the anchored
      anaphylactic antibodies largely impotent as protective factors against the
      standard destructive x-ray dose, even though sensitization preceded exposure to
      the x-rays. (4) An area treated with the standard destructive dose of x-rays is
      unable to produce or to anchor a sufficient amount of anaphylactic antibodies for
      protection from necrosis, when the x-ray treatment precedes the sensitization, or
      when the locally anchored anaphylactic antibodies are rendered functionally
      inactive by a general anaphylactic reaction. It is possible that the procedure of
      increasing the resistance of the skin to a destructive dose of x-rays by means of
      a previous sensitization with protein may be applicable in the treatment of
      certain types of inoperable disease, when it is important to use massive doses of
      x-rays. Animals which have been sensitized, or sensitized and reinjected with any
      undenatured alien protein, should not be reemployed as normal controls in any
      investigation unless trial has shown that these proteinized animals react
      quantitatively and qualitatively like normal animals. The presence of an abnormal
      reactor in a group of supposedly normal animals may be an indication of a
      previous proteinization.

PMID- 19868537
TI  - EFFECT OF SMALL DOSES OF X-RAYS ON HYPERTROPHIED TONSILS AND OTHER LYMPHOID
      STRUCTURES OF THE NASOPHARYNX.
AB  - 46 individuals with tonsils both hypertrophied and otherwise pathologically
      altered and some of whom had in addition adenoid masses and lymphoid deposits
      posterior to the pillars of the fauces, were given exposures to x-rays. In all
      but four cases the treatment was followed by marked atrophy of the tonsils and
      the other lymphoid deposits, attended by an opening and drainage of the tonsillar
      crypts. As this process progressed the previously enlarged tonsils assumed a
      smooth and normal appearance and the hemolytic bacteria-streptococci and
      staphylococci chiefly-which were often present in the affected tonsil disappeared
      usually within 4 weeks of the treatment.

PMID- 19868538
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      V. BACTERIUM PNEUMOSINTES AND CONCURRENT INFECTIONS.
AB  - During the course of animal experiments with the anaerobic filter-passing
      organisms cultivated from epidemic influenzal sources, certain pulmonary
      infections with ordinary bacteria have been observed. The experiments also have
      shown that the lungs of animals infected with Bacterium pneumosintes are less
      resistant than normal lungs to infection with ordinary bacteria. The
      demonstration of this fact invites a comparison of the course of these
      experimental bacterial infections with the sequence of postinfluenzal pneumonias
      attributable to similar organisms in man. These observations furnish additional
      proof of the identity of Bacterium pneumosintes and the active agent derived from
      the nasopharyngeal secretions of patients in the early hours of epidemic
      influenza.

PMID- 19868539
TI  - REACTIONS OF THE NASAL CAVITY AND POSTNASAL SPACE TO CHILLING OF THE BODY SURFACE
      : I. VASOMOTOR REACTIONS.
AB  - Devices are described by means of which the terminals of thermopiles may be held
      in stable apposition with the mucous membranes of the nasal cavity and postnasal
      space and local temperature variations thus followed. Chilling of the body
      surface has without exception caused depression of the temperature of the nasal
      mucosa surface, amounting in some instances to as much as 6 degrees C., and
      indicating marked reflex vasoconstriction and diminution of blood supply. With
      rewrapping, partial recovery of blood supply promptly occurs, although recovery
      has been incomplete within the duration of the experiments in ten of twelve
      instances. Application of the wires within the nasal cavity has usually caused
      pain and discharge of clear mucus, sometimes also lacrimation and sneezing. The
      rhinorrhea has occurred both on the side directly irritated and on the opposite
      side, although on the former more abundantly, and has apparently been little if
      at all affected by the diminished blood supply and shrinkage of the mucous
      membrane incident to chilling the body surface. Discharge from the nose has been
      at most a rare occurrence in experiments in which the nasal mucosa was not
      directly irritated. The temperature of the nasopharyngeal mucosa surface has also
      been depressed, typically between 1 degrees and 2 degrees C., with chilling of
      the body surface. This depression has also been shown to have local reflex
      vasoconstriction and ischemia as its basis. With rewrapping, prompt return toward
      normal occurs, but here also recovery of blood supply has in the majority of
      instances not been complete within the duration of the experiments. The
      thresholds of the chilling vasoconstrictor reflex to the mucous membranes of the
      nasal cavity and postnasal space, tonsil, oropharynx, and palate and the
      threshold of the reflex to the skin of the trunk have been found to be lower than
      the threshold of the like reflex to the skin of the forehead. Disrobing 'the
      warmly wrapped subject in a room a little below ordinary room temperature has
      been found sufficient to cause marked vasoconstriction in the sites of the former
      group, but only slight or no vasoconstriction in the forehead. A number of
      instances of cold or sore throat occurred among the subjects of the experiments,
      in several instances correlated with somewhat interesting bacteriologic findings
      which will be described elsewhere.

PMID- 19868540
TI  - STUDIES ON THE D'HERELLE PHENOMENON.
AB  - The inhibition produced by the lytic agent on the growth of Bacillus coli is
      greatly influenced by the reaction of the medium; it is faint in a slightly acid
      (pH 6.8) or neutral (pH 7) or even slightly alkaline broth (pH 7.4), but is much
      stronger in a more alkaline medium (pH 8 or 8.5). We have isolated from the
      original strain of Bacillus coli two types of organisms; one (Type S) is
      sensitive to the lytic agent, the other (Type R) is much more resistant. These
      types are distinguished also by other characteristics: Type S grows quickly in
      artificial medium and is non-motile; Type R grows more slowly, is extremely
      motile, much less phagocytable, and more virulent. Both types produce indole and
      ferment carbohydrates, with the exception of saccharose. Both types keep their
      individuality even after passage through a guinea pig. We have also demonstrated
      that even a culture of a single type, Type S for instance, is not a homogeneous
      whole but is made up of organisms of varying resistance to the lytic agent; only
      a few are resistant enough to overcome the strong action of the undiluted lytic
      agent. On the other hand, only a few as well are sufficiently sensitive to be
      dissolved even by very dilute lytic agent. This explains why dilute lytic agent
      spread on an agar plate seeded with Bacillus coli confines its action only to
      certain places and produces the small round areas of dissolution that d'Herelle
      considered as "colonies of bacteriophage." Moreover, we have observed the same
      localized action even with non-dilute lytic agent when submitting to its action
      cultures of greater resistance. Our original lytic agent was found to be
      specific; it acted exclusively on the coli with which the guinea pigs were
      injected. By allowing this original lytic principle to act on broth cultures of
      our two types of Bacillus coli, we have obtained two new filtrates. The first,
      resulting from dissolution of the sensitive Strain S, is specific as is the
      original filtrate. But with the second, obtained from the resistant Strain R, Dr.
      Wollstein has found a marked action on Shiga, on Flexner, and on Hiss dysentery
      bacilli. In consequence of this observation, we have been able, by a method of
      successive passages through appropriate strains, to extend the lytic power to
      other species, as typhoid and paratyphoid bacilli, and have obtained by this
      somewhat different technique results similar to those recently published by
      Bordet and Ciuca.

PMID- 19868541
TI  - THE CONCENTRATING ACTIVITY OF THE GALL BLADDER.
AB  - The bile coming at one time from different portions of the liver of the dog has
      nearly the same amount of pigment per cubic centimeter. With this determined we
      have studied the power of the gall bladder to concentrate bile directed to it,
      using as criterion the pigment strength of a sample collected throughout the
      period of experiment from a duct branch. The extent and rapidity of the
      concentration are alike remarkable. A gall bladder emptied at the beginning of
      one experiment and left to fill from the liver, concentrated the 49.8 cc. of bile
      reaching it in 22(1/2) hours to 4.6 cc., that is to say reduced its bulk 10.8
      times; while another bladder left distended with a bile of known constitution and
      receiving in addition fresh increments from the liver concentrated the secretion
      8.9 times in 22 hours. A series of five emptied bladders concentrated the bile
      coming to them in about 24 hours on the average 7.1 times, or a little more than
      the 6.4 times of seven organs left full. The conditions in both cases were
      relatively unfavorable to the withdrawal of fluid from the bile because this
      takes place by osmosis and diffusion, with the ultimate Delta always that of the
      blood, and the secretion in our animals was notably rich in solids as an indirect
      result of the operation. The rapidity with which fluid is withdrawn through the
      wall of the bladder may be judged from some experiments in which a bag was
      connected with the tip of the organ by a large cannula. Merely in its passage
      through the bladder the bile was concentrated 2.3 to 4.8 times. The finding
      indicates a potential source of error in observations upon samples of bile
      obtained from fistulous channels of which the bladder forms a part. The bile
      ducts do not withdraw fluid from the secretion they convey but tend to dilute it,
      as we shall show in a companion paper. The restriction of the concentrating
      activity to the receptaculum chyli is good evidence that the latter has special
      significance for the organism. The nature of this significance is briefly
      discussed.

PMID- 19868542
TI  - PHYSIOLOGICAL CAUSES FOR THE VARIED CHARACTER OF STASIS BILE.
AB  - The gall bladder and ducts exert opposite influences upon the bile. The ducts
      fail to concentrate and thicken it with mucus as the bladder does, but dilute it
      slightly with a thin secretion of their own that is colorless and devoid of
      cholates even when the organism is heavily jaundiced. The fluid may readily be
      collected into a rubber bag connected with an isolated duct segment. It continues
      to be formed against a considerable pressure, and, in the dog, is slightly
      alkaline to litmus, clear, almost watery, practically devoid of cholesterol, and
      of low specific gravity to judge from the one specimen tested. In obstructed
      ducts separated from the gall bladder, or connecting with one so changed
      pathologically that the concentrating faculty has been lost, such fluid gradually
      replaces the small amount of bile originally pent up. It is the so called "white
      bile" of surgeons. When obstructed ducts connect with an approximately normal
      gall bladder the stasis fluid is entirely different, owing to the bladder
      activity. At first there accumulates in quantity a true bile much inspissated by
      loss of fluid through the bladder wall, darkened by a change in the pigment, and
      progressively thickened with bladder mucus. As time passes duct secretion mingles
      with the tarry accumulation and very gradually replaces it. The inspissation of
      the bile, as indicated by the pigment content, is at its greatest after only a
      day or two of stasis. The differing influences of the ducts and bladder upon the
      bile must obviously have much to do with the site of origin of calculi and their
      clinical consequences. The concentrating activity of the bladder cannot but be a
      potent element in the formation of stones. We have discussed these matters at
      some length. Intermittent biliary stasis is admittedly the principal predisposing
      cause of cholelithiasis; and the stasis is to be thought of as effective, in many
      instances at least, through the excessive biliary inspissation for which it gives
      opportunity. In this way a normal gall bladder can become, merely through
      functional activity, a menace to the organism. In patients with the tendency to
      stones frequent feedings may lessen the danger of their formation.

PMID- 19868543
TI  - STUDIES ON BACTERIAL NUTRITION : II. GROWTH ACCESSORY SUBSTANCES IN THE
      CULTIVATION OF HEMOPHILIC BACILLI.
AB  - The hemophilic bacteria of which Bacillus influenzae serves as a type require for
      their growth two distinct and separable substances, both of which are present in
      blood and neither of which alone suffices. These substances are (a) a vitamine
      like substance which can be extracted from red blood corpuscles, from yeast, and
      from vegetable cells, which is relatively heat-labile and absorbed from solution
      by certain agents; (b) a so called X substance which is present in red blood
      cells, is heat-stable, and acts in minute amounts.

PMID- 19868545
TI  - STUDY OF TRANSFUSED BLOOD : II. BLOOD DESTRUCTION IN PERNICIOUS ANEMIA.
AB  - Evidence is presented to show that there is no hemolytic toxin producing the
      anemia in pernicious anemia. Partial evidence is presented to show that the
      periods of active blood destruction which are seen as the exception in pernicious
      anemia cases during a series of transfusions are due to the activity of the blood
      destroying organs of the body rather than to the intrinsic weakness of the
      pernicious anemia blood corpuscle. It is questionable whether blood destruction
      is as important a factor in producing the anemia of pernicious anemia as it is at
      present usually assumed to be.

PMID- 19868544
TI  - STUDY OF TRANSFUSED BLOOD : I. THE PERIODICITY IN ELIMINATIVE ACTIVITY SHOWN BY
      THE ORGANISM.
AB  - Group IV transfused blood in a recipient of unlike group is eliminated by a blood
      destroying activity of the body. This blood-destroying activity is periodic both
      in men and women, and in women coincident with menstruation. The elimination of
      the transfused blood probably takes place as part of a period of blood-destroying
      and blood-producing activity of the body, although direct evidence to this effect
      is so far lacking.

PMID- 19868546
TI  - EXPERIMENTAL SYPHILIS IN THE RABBIT : VII. AFFECTIONS OF THE EYES.
AB  - From the study of a number of instances of eye infection in the rabbit, it was
      found that a variety of affections might occur following scrotal or testicular
      inoculations of Treponema pallidum. Those observed included ciliary injection,
      conjunctivitis, keratitis, and iritis which might occur separately or in
      combination with one another, except that keratitis and iritis were always
      accompanied by a reaction in the ciliary vessels and usually by a conjunctivitis.
      Several forms of each of these affections were described, and while some of them
      were regarded as presenting a very characteristic picture, it was recognized that
      the conditions present in other cases were not sufficiently distinctive to permit
      of a clinical diagnosis. With a few exceptions, however, the pathology of the
      lesions was sufficient to identify them as processes of a syphilitic nature. It
      was also found that this group of lesions usually arose from a common focus of
      infection which was located in the episcleral tissues immediately surrounding the
      cornea. From this point, the infection tended to spread to the conjunctiva and
      the cornea, or toward the canal of Schlemm and the spaces of Fontana and thence
      to the ciliary body, the iris, and the choroid. The localization of the lesion
      and the mode of extension were held to be responsible for the combination of
      manifestations usually observed. From an analysis of the circumstances under
      which affections of the eyes occurred, it was found that the great majority of
      them occupied a definite position in the scheme of tissue reactions, being the
      only generalized lesions developed or the last type of lesion to appear. These
      facts, together with the unusual frequency of relapse in these affections, were
      believed to indicate that a low degree of protection was conferred upon these
      tissues by reactions taking place elsewhere and that the protection afforded by
      the local reaction was of a feeble character. This deduction was in part
      confirmed by the fact that it was found to be possible to increase or decrease
      the incidence of eye lesions by the use of experimental means which varied the
      scheme of reaction in animals inoculated with a given strain of Treponema
      pallidum.

PMID- 19868547
TI  - NOTE ON THE PRESERVATION OF STOCK STRAINS OF TREPONEMA PALLIDUM AND ON THE
      DEMONSTRATION OF INFECTION IN RABBITS.
AB  - Experiments carried out on rabbits infected with Treponema pallidum showed that
      there was a constant invasion and localization of the organisms in the
      superficial lymph nodes, that the infection persisted indefinitely, and that
      organisms could be recovered at any time from such nodes as the popliteals. Based
      upon these observations, a method is proposed for the preservation or recovery of
      stock strains of Treponema pallidum and for the demonstration of infection in
      rabbits.

PMID- 19868548
TI  - EXPERIMENTAL RICKETS IN RATS : I. A DIET PRODUCING RICKETS IN WHITE RATS, AND ITS
      PREVENTION BY THE ADDITION OF AN INORGANIC SALT.
AB  - 1. A simple diet is presented which regularly induced rickets in young rats. 2.
      The substitution of 0.4 per cent secondary potassium phosphate for a small part
      of calcium lactate in this diet completely inhibited the development of rickets.
      3. Quantitative determinations of calcium in the bodies of parallel rats showed a
      marked increase of calcium content in the rats receiving the added phosphate over
      those which developed rickets. 4. While it is thus shown by x-rays and by
      histological examinations and by quantitative chemical analysis that added
      potassium phosphate increased the assimilation and normal deposition of calcium,
      it may be the quantitative relationship between the inorganic ions rather than
      actual deficiency of any one of them which was here the determining factor in the
      cause or prevention of rickets. Our experiments and conclusions do not exclude
      the possibility of other causes of rickets than those here discussed.

PMID- 19868549
TI  - STUDIES ON THE PNEUMONIC EXUDATE : I. EFFECT OF PRESERVATION, TEMPERATURE,
      DIALYSIS, AND SALT CONCENTRATION ON THE ENZYME IN THE PNEUMONIC LUNG.
AB  - 1. The enzyme present in the pneumonic lung exudate still remains active after
      preservation for 18 months. 2. The enzyme is active at incubator temperature
      before and after heating to 65 degrees C. for 1 hour. It is slightly active at
      room temperature and inactive after heating at 75 degrees C. for 1 hour. 3.
      Dialysis of the enzyme is not demonstrable. 4. Activity persists when the enzyme
      is mixed with concentrations of sodium chloride varying from normal to thirty-two
      times normal.

PMID- 19868550
TI  - STUDIES ON THE PNEUMONIC EXUDATE : II. THE PRESENCE OF ENZYME AND ANTIENZYME IN
      THE PNEUMONIC LUNG. LOCAL FERMENT-ANTIFERMENT BALANCE.
AB  - The purulent sputum obtained during life and the exudate at autopsy from the
      later stages of lobar pneumonia commonly erode the surface of Looffler's blood
      serum. Cellular material obtained from the pneumonic lung in an early stage of
      lobar pneumonia failed to erode the surface until washed with normal saline
      solution. Mixtures of washed pneumonic cellular material and normal human serum
      fail to erode Loffler's blood serum when the amount of cellular material is less
      than one part of cells to approximately three parts of serum. Erosion occurs when
      the cellular material exceeds this amount in the ratio.

PMID- 19868551
TI  - STUDIES ON THE PNEUMONIC EXUDATE : III. THE PRESENCE IN THE PNEUMONIC EXUDATE OF
      A LARGE AMOUNT OF SPECIFIC ANTIGEN.
AB  - In lobar pneumonia due to the fixed types of pneumococci a specific precipitin
      reaction is obtained when the pneumonic exudate is mixed with the homologous
      antipneumococcic serum.

PMID- 19868552
TI  - STUDIES ON THE PNEUMONIC EXUDATE : IV. THE PRESENCE IN THE PNEUMONIC LUNG OF A
      SOLUBLE SUBSTANCE INHIBITING AGGLUTINATION BY THE HOMOLOGOUS SERUM.
AB  - Specific agglutinins for the homologous pneumococcus are lacking or present only
      in small amount in the pneumonic exudates due to the fixed types of pneumococci.
      Suspensions of fixed types of pneumococci in the supernatant fluid obtained after
      centrifuging the mash of the pneumonic lung give positive agglutination tests in
      dilutions not higher than equal parts of suspension and supernatant fluid (1:2).
      The pneumonic lung contains a soluble substance inhibiting agglutination of the
      fixed types of pneumococci by the homologous antipneumococcus serum.

PMID- 19868553
TI  - STUDIES ON COMPLEMENT FIXATION : I. THE RATE OF FIXATION OF COMPLEMENT AT
      DIFFERENT TEMPERATURES.
AB  - It is shown by complement fixation studies with protein antigens and specific
      immune rabbit sera that the rate of fixation of complement is determined by the
      concentration of antibodies in the immune sera, that the greater part of fixation
      of complement takes place during the 1st hour, and that fixation is practically
      completed at the end of 4 hours at ice box temperature. It is further shown that
      the rate. of fixation of complement is practically the same at ice box, room, and
      water bath temperatures, the tendency being for slightly stronger fixation at ice
      box temperature.

PMID- 19868554
TI  - MEASUREMENT OF THE GROWTH OF TISSUES IN VITRO.
AB  - 1. A technique has been developed by which two fragments of tissue, put in
      identical media, can grow at almost the same rate. 2. A method of measuring the
      growing tissue is described. 3. The differences observed in the rate of growth of
      two fragments of the 9 year old strain of connective tissue, cultivated in
      identical media and measured according to this technique, are less than 10 per
      cent.

PMID- 19868555
TI  - STUDIES ON PNEUMOCOCCUS IMMUNITY : I. ACTIVE IMMUNIZATION OF MONKEYS AGAINST
      PNEUMOCOCCUS TYPE I PNEUMONIA WITH PNEUMOCOCCUS TYPE I VACCINE.
AB  - 1. The subcutaneous inoculation of monkeys with three large doses of Pneumococcus
      Type I vaccine confers on them a complete immunity against experimental
      Pneumococcus Type I pneumonia. 2. The intravenous inoculation of small doses of
      Pneumococcus Type I vaccine also confers complete immunity against the homologous
      type of pneumonia. 3. Specific protective bodies may or may not be present in the
      serum of monkeys vaccinated against Pneumococcus Type I. There appears to be no
      intimate relation between active immunity against pneumonia and the presence or
      absence of protective substances in the serum of the vaccinated animal.

PMID- 19868556
TI  - DATA ON THE DEVELOPMENT OF HETERAKIS PAPILLOSA IN THE FOWL.
AB  - In observations on the development of the ova of Heterakis papillosa in cultures,
      it was found that they failed to develop at a temperature ranging from 2.5-8
      degrees C., but developed slowly at a temperature of 11.5-13.5 degrees C. The
      minimum temperature for development seems to lie between 8 degrees and 11.5-13.5
      degrees C. At temperatures ranging in various cultures from 18-29 degrees C. ova
      developed to their final stage in 7 to 12 days. Undeveloped ova subjected to a
      freezing temperature for a period of 4 days were viable at the end of that time.
      Fully developed ones remained alive when exposed out of doors for a period of 7
      days at a temperature ranging from 5-62 degrees F. Undeveloped ova survived
      desiccation at room temperature for a period of 16 days, but not for 41 days.
      Fully developed eggs were alive after desiccation for 18 days, but not after 49
      days. In another instance they were no longer viable after 10 days. Embryos
      within ova kept in physiological salt solution at room temperature survived
      during a period of a little over 12 months. Fully developed ova kept in soil
      outdoors under circumstances approaching natural conditions contained living
      embryos after a period of 8 months. From a study of a series of artificially
      infested chickens killed at short intervals it appears that the ova of Heterakis
      hatch in the small intestine and the larvae pass by way of the small and large
      intestines to the ceca where they undergo development to maturity. Larvae found
      in the mucosa of the ceca were not in an encysted condition. Feeding of numerous
      artificially incubated ova may lead to a light infestation, the cause of which
      has not been definitely determined. A period of 57 days was required for larvae
      to reach maturity in a host. The entire cycle from egg to adult requires a
      minimum time of about 64 days. A brief study of the growth and development of
      larvae within the host has been made. No evidence was found of a migration
      through the tissues. A few penetrate into the mucosa of the ceca.

PMID- 19868557
TI  - LYMPHOPENIA FOLLOWING EXPOSURES OF RATS TO "SOFT" X-RAYS AND THE beta-RAYS OF
      RADIUM.

PMID- 19868558
TI  - THYROIDECTOMY AND PARATHYROIDECTOMY WITH RELATION TO THE DEVELOPMENT OF IMMUNE
      SUBSTANCES.
AB  - 1. After thyroidectomy with partial parathyroidectomy the maximum and average
      hemolytic titers of the sera of rabbits injected intravenously with sheep blood
      are equal to or higher than those of normal animals similarly injected. 2.
      Thyroidectomy with partial parathyroidectomy does not inhibit antibody
      production. This fact is in accord with the results of Garibaldi, Launoy and Levy
      Bruhl, Lerda and Diez, and others. 3. Thyroidectomy with partial
      parathyroidectomy does not cause serious disturbance in the adult rabbit. If the
      operation is performed properly, the animals survive and only moderate cachexia
      develops in time. 4. After complete thyroparathyroidectomy a small proportion of
      the animals survive even after developing very severe tetany. Those that recover
      do not show further signs of serious disturbance, but in time develop a moderate
      degree of cachexia no greater than that of the thyroidectomized animals. 5.
      Thyroparathyroidectomized rabbits develop anti-sheep hemolysin of a uniformly low
      titer-on an average one-fifth that of the controls. 6. Injection of bovine blood
      into rabbits that survived complete thyroparathyroidectomy from 1 to 2 months
      previously results in the production of hemolysin of a uniformly low titer
      compared with that of normal animals similarly treated.

PMID- 19868559
TI  - CRISTISPIRA IN NORTH AMERICAN SHELLFISH. A NOTE ON A SPIRILLUM FOUND IN OYSTERS.
AB  - Ten varieties of North American shellfish were examined for the occurrence of
      Cristispira in their styles. A cristispira was found in various numbers in Ostrea
      virginiana, Venus mercenaria, and Modiola modiolus, but none in Ensis americana,
      Mya arenaria, Mactra solidissima, Pecten irradians, Mytilus edulis, Fulgur
      canaliculatus, or Nassa obsoleta. Of 298 oysters, only 128 showed the crystalline
      styles, in which cristispiras were present in 99. Active cristispiras were found
      in 59 styles only and degenerated forms in the remaining 40. In 110 clams (Venus
      mercenaria) 70 styles were found, and only 8 of these contained cristispiras; 5
      yielded active and the other 3 degenerated cristispiras. In 97 modiolas there
      were 73 styles, only 4 of which contained cristispiras. The physical properties
      of the crystalline styles of these shellfish varied considerably. The styles of
      the oysters were moderately soft, and when exposed to the air or mixed with sea
      water they underwent liquefaction, forming a clear, viscid material. The styles
      from clams and modiolas were opaque and were more firm, not easily crushed even
      in a mortar. The styles of the scallops were the most solid of all the styles
      examined. It happened that the softer the styles, the more frequent was the
      occurrence of the cristispira; in fact, no cristispira was detected in styles
      other than those of oysters, clams, and modiolas, of which oysters had the
      softest styles and the largest percentage of cristispira invasion. The following
      observations were made regarding the structure of the cristispira found in
      oysters. The body is a long, flexible cylinder, with blunt extremities, towards
      which the diameter gradually diminishes. In motion the body rapidly stretches and
      contracts, forming in the contracted state several serpentine undulations. A
      membranous appendage (Gross' crista) winds about the body throughout its entire
      length. The inner margin is in connection with the body, the outer margin is free
      and is distinctly heavier. The latter is undulatory; that is, the width of the
      membrane, or crista, is narrower at some points than at others. The membrane is
      composed of numerous fine fibrils running in a roughly parallel or slightly
      oblique course, showing interwoven narrow meshes; at the outer margin there is a
      dense smooth ridge. The contour of the body is highly refractive, as if
      possessing a cell membrane. The interior structure, as revealed by dark-field
      illumination, is an almost homogeneous, less refractive substance, but there are
      present minute highly refractive granules more or less symmetrically arranged.
      There is no definite cross-bar or chambered structure. On the other hand, when
      vital staining with brilliant cresyl blue is applied, there appear numerous
      paired masses of lavender hue at fairly regular intervals, suggesting the cross
      bar aspect of a stained specimen. In a few specimens there was seen a dim outline
      of cross-bar effect. Neutral red, Bismarck brown, and crystal violet all bring
      out deeply stained granules and reticular structure but no definite cross-bars.
      The crista is a fibrillar structure, connected with the body at its inner edge.
      The outer margin is a thickened bundle of fibrils running an undulating course
      along the entire length of the crista. The crista is elastic and when detached
      from degenerated organisms assumes a rather regularly wound spiral, consisting of
      longitudinal bundles of fibrils (Figs. 36 to 38). A fragment of two or three
      waves may be encountered in a preparation containing many degenerated organisms
      (Fig. 39). The composition of the crista can best be studied in degenerated
      remains of the organism. During the life of Cristispira it is stretched or
      relaxed according to the contraction or extension of the body. The elasticity of
      the crista appears to furnish the organism with a propelling and rotating power
      upon its extension after being drawn tightly to the body by some contractile
      apparatus (myoneme) present somewhere within the cell body. The crista serves as
      a rudder and propeller for the swimming organism. It is interesting to compare
      here the elastic and regularly waved flagella of certain bacteria and
      spirochetes; it is possible that the crista of Cristispira is a highly modified
      form of flagella. The nature of the substance which stains dark blue with
      Giemsa's stain is not known, but it does not give a chromatin reaction. By
      Heidenhain's iron-hematoxylin method it takes a dark grayish tint, similar to the
      cell wall or crista, which are also dark gray. This substance was regarded by
      Gross and Zuelzer as volutin, which is of nutritive origin. It is probable that
      there are also embedded within it minute chromidial elements. Multiplication is
      by transverse fission. Cristispira balbianii is parasitic and does not survive
      more than a few days in ordinary sea water emulsion, even at its optimum
      temperature. In its natural habitat, or the crystalline style, it is usually
      pure, but is sometimes found in association with a tiny spiral organism
      (Spirillum ostreae). The cristispiras in the styles seem to diminish rapidly when
      oysters are collected from their beds and transferred elsewhere; oysters kept in
      tanks or cars for several days do not contain the cristispiras, and in opened
      oysters the styles disappear promptly at room temperature. All efforts to
      cultivate this organism have failed.

PMID- 19868560
TI  - THE MULTIPLICATION OF FIBROBLASTS IN VITRO.
AB  - 1. It may be concluded that, under the conditions of the experiments and within
      the limits of accuracy of the method, the temporary multiplication of fibroblasts
      cultivated in the plasma of an adult animal is not due to the serum. It may be
      attributed to the presence of a small amount of embryonic juice within the tissue
      itself. 2. The indefinite multiplication of fibroblasts in a medium composed of
      adult plasma and of embryonic juice is due neither to the serum nor to the
      fibrin. It depends entirely on substances contained in the embryonic juice. 3.
      There is a definite relation between the rate of growth and the concentration of
      the embryonic juice in the medium.

PMID- 19868561
TI  - CICATRIZATION OF WOUNDS : XI. LATENT PERIOD.
AB  - 1. The latent period of cicatrization varies generally from 5 to 7 days. 2. It
      stops abruptly and contraction starts with its maximum velocity. 3. The formula
      of du Nouy applies to the beginning of the contraction period as well as to the
      subsequent periods.

PMID- 19868562
TI  - THE DIASTATIC ACTIVITY OF THE BLOOD IN EXPERIMENTAL HYPERGLYCEMIA.
AB  - 1. The diastatic activity of the blood is not materially changed by the
      subcutaneous injection of phlorhizin, uranyl nitrate, or adrenalin. 2. The
      diastatic activity of the blood is not affected by puncture of the floor of the
      fourth ventricle. 3. The diastatic activity of the blood is definitely increased
      by subcutaneous injections of morphia when a marked hyperglycemia is produced.
      The same phenomenon appears in asphyxia. 4. Complete pancreatectomy in dogs
      produces an increase in the diastatic activity of the blood. 5. The diastatic
      activity of the blood is not altered by the diet. 6. Ether anesthesia, alone,
      produces a very slight tendency to increase in the diastatic activity of the
      blood. 7. Repeated periodic small hemorrhages (4.5 cc.) produce no change in the
      diastatic activity of the blood until a definite color anemia results, when a
      slight tendency toward increase occurs simultaneously with the rise in blood
      sugar. 8. The diastatic activity of the blood is not proportional to the
      concentration of the sugar in the blood.

PMID- 19868563
TI  - TYPHUS FEVER AMONG RECENT IMMIGRANTS : EXPERIMENTAL DEMONSTRATION OF THE IDENTITY
      OF THIS DISEASE WITH EUROPEAN EPIDEMIC TYPHUS FEVER.
AB  - It is experimentally demonstrated in the guinea pig that the blood from an
      infected Czecho-Slovakian arriving at the Port of New York from Italy contained
      the virus of typhus fever and that this strain is identical with the epidemic
      virus present in man and louse in Poland.

PMID- 19868564
TI  - EXPERIMENTAL STUDIES ON INFLAMMATION : I. THE INFLUENCE OF CHEMICALS UPON THE
      CHEMOTAXIS OF LEUCOCYTES IN VITRO.
AB  - 1. Wright's method for the study of chemotaxis of leucocytes in vitro, slightly
      modified, has been found to be most satisfactory in the estimation of the degree
      of chemotaxis of various substances, because it is possible to make an exact
      quantitative determination of the leucocytes that have migrated from the blood
      clot and adhere to the surfaces containing the tested substance. 2. The calcium
      ion is the only inorganic ion per se which is found to be positively chemotactic
      under the conditions of these experiments. It is markedly chemotactic in all
      concentrations and in all combinations, except the citrate. Here the negative
      chemotaxis of the citrate ion neutralizes the positive chemotaxis of the calcium
      ion, and neutrality of chemotactic effect results. 3. The sodium and magnesium
      ions themselves are neutral. Magnesium and sodium salts are dependent upon the
      negative ion with which the magnesium or sodium is combined for such positive or
      negative chemotaxis as is exhibited. All the phosphates of sodium, whether tri-,
      di-, or monobasic salts, are markedly positively chemotactic, and when combined
      with other reagents which are themselves neutral or negatively chemotactic,
      produce marked positive chemotaxis. The blood of a person who has taken
      phosphates either by mouth or intravenously shows a great increase in chemotaxis
      with sodium phosphate, with calcium chloride, and even with sodium chloride which
      is ordinarily neutral. 4. All potassium salts are negatively chemotactic. 5. Many
      substances act synergistically as regards chemotaxis; e.g., when strontium and
      magnesium salts are mixed there is a marked increase in chemotaxis. Sodium
      phosphate acts synergistically with calcium chloride. 6. Mercury salts fix the
      leucocytes in this method so that their influence on chemotaxis cannot be
      determined. 7. Morphine and morphine salts are positively chemotactic; this is
      contrary to the results obtained by others with different methods. 8. Substances
      which produce a very acute inflammation, such as cantharidin, histamine, or
      turpentine, are found to be positively chemotactic by this method, but
      substances, such as mustard gas, which produce a marked necrotizing effect are
      found to be negatively chemotactic, or neutral, though physiologically they would
      appear to be positively chemotactic. 9. All amino-acids and amines are positively
      chemotactic to a certain extent. It seems that the longer the carbon chain, the
      greater the degree of chemotaxis, though this is not absolute. Tyramine is one
      exception to this, for it causes a peculiar clumping of the cells, so that it is
      impossible to count the number adhering, and thus determine whether or not
      tyramine is positively chemotactic. 10. The time that the blood of animals is
      examined after eating makes a marked difference in the number of cells adhering,
      for shortly after eating, within 30 minutes, very many more cells will adhere to
      the agar than at a later time. 11. The blood of different species of animals
      reacts differently towards different reagents. The chemical composition of these
      agents seems to have nothing to do with this difference in reaction as far as we
      could determine. 12. With frozen serial sections it has been found that the depth
      of penetration of the leucocytes into the agar is proportional to the positive
      chemotaxis produced by the substance combined with the agar, as demonstrated by
      the number of leucocytes adherent to the walls of the test chambers.

PMID- 19868565
TI  - WANDERING CELLS, ENDOTHELIAL CELLS, AND FIBROBLASTS IN CULTURES FROM HUMAN LYMPH
      NODES.
AB  - Wandering cells migrate from cultures of human lymph nodes after 2 or 3 hours
      incubation; they are actively ameboid and phagocytic. Endothelial cells appear in
      the plasma clot after 24 to 48 hours incubation. They are relatively inactive and
      less phagocytic. Fibroblasts are seen after 48 hours incubation. They are
      inactive and not phagocytic. The probable origin of wandering cells from
      endothelial cells is discussed.

PMID- 19868566
TI  - THE INFLUENCE OF THYROID PRODUCTS ON THE PRODUCTION OF MYOCARDIAL NECROSIS.
AB  - An experimental study upon the demonstrable effects of large doses of dried
      thyroid gland and thyroxin upon the myocardium of rabbits has been made. Animals
      under such treatment show characteristic clinical symptoms with definite,
      although relatively slight, myocardial lesions. Similarly treated animals which
      have, in addition, been subjected to chloroform anesthesia show more striking,
      widespread myocardial necrosis. These experiments indicate very distinctly that
      chloroform as an anesthetic in cases of hyperthyroidism is apt to be
      exceptionally detrimental to the myocardium, and should be avoided.

PMID- 19868567
TI  - CICATRIZATION OF WOUNDS : XII. FACTORS INITIATING REGENERATION.
AB  - As long as the wounds were protected by a connective tissue dressing against
      mechanical, chemical, and bacterial irritations, no evidence of cicatrization was
      found. The complete or partial failure of four experiments was due to the
      slipping of the inner dressing from the wound, mechanical irritation by the
      gauze, and infection. In the two experiments in which the connective tissue was
      maintained at the surface of the wound, there was no beginning of cicatrization,
      although 25 and 18 days respectively had elapsed since the operation, while in
      the control wound the duration of the latent period did not exceed 5 or 6 days.
      The experiments were interrupted after the second or third inspection, on account
      of the technical impossibility of again applying to the wounds a non-irritant
      dressing. It is probable that the wounds could have been kept for a much longer
      time in a condition of quiescence. While it is not known whether cicatrization
      could be prevented for an indefinite period, there is no doubt that the mechanism
      of regeneration is not set in motion at the usual time, when all external
      irritations are suppressed. It appears, therefore, that under ordinary
      conditions, cicatrization is not initiated by an internal factor. On the
      contrary, the application of turpentine, chick embryo pulp, and staphylococci
      decreased markedly the length of the latent period, which was often reduced to
      less than 2 days. This fact demonstrated the importance of external factors in
      the initiation of cicatrization. It seems that the mechanism of regeneration has
      become adapted to the ordinary conditions of life of the animals. A small wound
      will begin to cicatrize sooner if slightly infected, as practically always
      happens, than if it were thoroughly protected by a non-irritant dressing.

PMID- 19868568
TI  - REMOTE RESULTS OF COMPLETE HOMOTRANSPLANTATION OF THE CORNEA.
AB  - 1. A flap composed of the entire thickness of the cornea of a cat was
      transplanted to the cornea of another cat, and was found to be perfectly
      transparent 2 years after the operation. 2. The curvatures of the cornea appeared
      to be normal.

PMID- 19868569
TI  - REMOTE RESULTS OF OPERATIONS ON THE PULMONARY ORIFICE OF THE HEART.
AB  - Eight animals died from 1 to 6 years after the operation, from undetermined
      diseases, or from pneumonia. Two animals are still alive 7 years after the
      operation. 1. Condition of the Pleural and Pericardial Cavities.-In the first
      experiments, extensive pleural and pericardial adhesions were observed 1 year and
      more after the patching of the pulmonary artery. There was also a great deal of
      fibrous tissue between the pulmonary artery, the aorta, and the left auricle. In
      the other experiments, the adhesions of the lungs, pleura, and pericardium were
      less marked. This was due to some improvements in the technique of handling the
      viscera. At the time of the operations, it was hoped that no pleural or
      pericardial adhesions would occur. Great care was taken not to injure the
      endothelial surfaces by rough handling or by sponging. No blood was allowed to
      flow into the pleural cavity. The surface of the pericardium was protected by
      fine silk membranes. The pleural cavity was occluded by thick pads made of cotton
      and Japanese silk. It seemed that the serous surfaces were almost completely
      protected against infection and mechanical irritation. The occurrence of primary
      pleurisy and pericarditis was prevented by this technique. But the development of
      adhesions in several of the experiments shows that the procedures for the
      handling of the viscera should be perfected. 2. Condition of the Arterial Wall.
      In the experiments in which the orifice was patched, a slight dilatation of the
      artery was observed. It was not possible to ascertain from the specimen preserved
      in formaldehyde whether or not there was an insufficiency of the valves. It is
      probable that there was no leakage, as in none of these cases could any diastolic
      murmur be heard 6 months after the operation. The only animal which presented
      clinical evidence of pulmonary insufficiency died during the War. The normal
      condition of the pulmonary orifice was due to the incision which did not extend
      far enough on the ventricle, and to the power of redintegration possessed by an
      organ which is not diseased. The cicatrization of the grafted flap was excellent.
      Its outline could not be seen on the external side of the wall. Even after
      opening the artery, the transplant could not be located easily. However, in
      Experiment 1 the anterior wall of the artery showed a depression about 7 or 8 mm.
      wide, 18 mm. long, and 2 or 3 mm. deep, behind and above the anterior valve. But
      the flap was made of human artery, and it is known that a heteroplastic graft
      always undergoes some dilatation. When transplants of dog tissue were used, no
      dilatation occurred and the location of the patch could hardly be detected. In
      Experiment 7, 6 years after the operation, the endothelial surface was smooth,
      glistening, and no scar could be seen. However, the upper and lower parts of the
      incision were marked by a slight depression of the wall. The presence of the
      patch was detected by a distinct thickening of the wall. Although the edges of
      the incision had not been sutured to the edges of the flap, the endothelial
      surface was quite smooth. A transverse section of the artery was made through the
      middle part of the flap in Experiment 4. It showed the width of the arterial
      opening and the way in which the transplant became adherent to the arterial wall.
      The examination of these four specimens demonstrated that, in spite of the
      unfavorable location of the graft, an excellent union had taken place. It showed
      that homoplastic or heteroplastic tissue can be transplanted onto the pulmonary
      artery as well as onto the smaller arteries. Where the arterial wall had simply
      been incised without interposition of a patch, a linear scar was always found. 6
      years after the operation, the incision used in the course of an operation for
      cauterization of the sigmoid and sutured with heavy thread was transformed into a
      linear scar and the surface of the intima was quite smooth. 3. Condition of the
      Sigmoid Valves.-In three experiments, the sigmoid valves had been cauterized
      along their margin and their point of insertion in the artery. One of the animals
      was still living 7 years after the operation. There was no diastolic murmur. The
      other animals died 3 and 6 years after the operation. The valves were thin and
      transparent, and quite normal. However, one of the valves showed two holes, one
      near the base and the other near the margin. The animal on which the section of
      the right posterior valve without suture was performed, died 2 or 3 years after
      the operation. The edges of the incision had not united. They were thickened and
      the whole valve was rigid. The surface was rough and irregular. No permanent
      result was obtained by the union of two sigmoid valves by a stitch. There was no
      stenosis of the orifice, and no union of the valves 4 years after the operation.
      The stitch had disappeared. There was some scar tissue at the common point of
      insertion of the posterior valves, which were more rigid and showed thickened
      edges. 7 years after the section and suture of a sigmoid had been performed, the
      animal was still living and in good health. No diastolic murmur could be
      detected.

PMID- 19868570
TI  - GROWTH OF FIBROBLASTS AND HYDROGEN ION CONCENTRATION OF THE MEDIUM.
AB  - 1. The rate of growth of fibroblasts is markedly modified by slight changes in
      the hydrogen ion concentration of the medium. The curves expressing the rate of
      growth in function of the hydrogen ion concentration of the medium are nearly
      symmetrical on both sides of the maximum. 2. The optimum growth of fibroblasts
      occurs at pH 7.4 to 7.8. A slight change from this reaction has a remarkable
      influence on the rate of growth. 3. Fibroblasts show more resistance to higher
      alkalinity than to higher acidity. They grew for only four to six generations in
      a medium having a pH of 5.5, and for more than ten generations in one of 8.5. 4.
      The influence of different hydrogen ion concentrations on fibroblasts was only of
      a quantitative nature.

PMID- 19868571
TI  - STUDIES ON BACTERIAL NUTRITION : III. PLANT TISSUE, AS A SOURCE OF GROWTH
      ACCESSORY SUBSTANCES, IN THE CULTIVATION OF BACILLUS INTLUENZAE.
AB  - 1. Growth of Bacillus infiuenzoe depends on two distinct and separable
      substances. 2. These growth accessory substances are present in blood. 3. They
      occur in plant as well as in animal tissue. 4. Sterile, raw potato will serve as
      a substitute for blood in the cultivation of Bacillus influenzoe.

PMID- 19868572
TI  - STUDIES ON THE PHENOMENON OF D'HERELLE WITH BACILLUS DYSENTERIAE.
AB  - It has been shown that a lytic fluid for dysentery bacilli can be obtained from
      the peritoneum of the guinea pig by intraperitoneal inoculation of live dysentery
      bacilli, and that the lytic action of such a fluid is not strictly specific, but
      that it exerts a group action on the dysentery-colon-typhoid group of bacilli. A
      lytic fluid with similar effects was obtained from a child dying of Flexner
      dysentery infection, and an anti-colon bacillus lytic fluid from a child who died
      of intussusception with colon bacillus peritonitis. The action of the lytic fluid
      on the dysentery bacilli, both in vivo and in vitro, is to divide the culture
      into sensitive and resistant strains, and the latter can be carried to a degree
      of very marked, if not complete resistance to lysis. Such resistant strains are
      not lysogenic, nor are they agglutinable. The sensitive strains are lysogenic and
      agglutinable. Varying degrees of sensitive and resistant bacilli exist in a
      single culture. The sensitive bacilli gradually lose the lysogenic property which
      they acquired under special conditions, but the very resistant bacilli never
      acquire that property. It is conceivable that the resistant strains are
      responsible for the untoward outcome of disease in human beings. Theoretically
      the administration of lytic fluid should rid the intestinal tract of most of the
      infecting bacilli, and only if completely resistant bacilli in large numbers
      remain unacted on is the outcome of the disease a fatal one.

PMID- 19868573
TI  - THE BIOLOGICAL AND THE SEROLOGICAL REACTIONS OF INFLUENZA BACILLI PRODUCING
      MENINGITIS.
AB  - 1. An attempt has been made to standardize the cultural and the serological work
      on influenza bacilli. As technique and knowledge improve cultural and serological
      characteristics may be shown to be different from those reported here. The
      results are constant enough for comparison as they were obtained under as nearly
      similar conditions as possible. 2. Of thirteen meningitic strains of Bacillus
      influenzae isolated by different workers during a period of 7 years, eleven are
      alike culturally and fall into two groups by absorption of agglutinin tests;
      seven are in Group 1, three in Group 2, with one intermediate strain. Two strains
      stand alone culturally and serologically. 3. Four blood culture strains from
      children with pneumonia differ from each other culturally and serologically. When
      these strains show a relation culturally to members of the meningitic group this
      is not confirmed by serological reactions. When more respiratory strains are
      studied there may be found among them some similar culturally and serologically
      to the meningitic group. 4. Evidence has been set forth in favor of the
      possibility that a certain group of influenza bacilli may have risen to a level
      of pathogenicity to produce a disease picture known as influenzal meningitis. If
      this be true an attempt should be made to obtain a potent serum for treatment.

PMID- 19868574
TI  - STUDIES ON THE TUBERCULIN REACTION AND ON SPECIFIC HYPERSENSITIVENESS IN
      BACTERIAL INFECTION.
AB  - The work reported in the preceding sections justifies, we think, a number of
      definite conclusions. In addition to this, some of the experiments indicate a
      line of thought which may lead to considerable alteration in our conceptions,
      both of phenomena of bacterial hypersensitiveness and of infection. 1. In guinea
      pigs two fundamentally different types of intradermal reactions may be observed.
      One of these is the immediate, transitory reaction which develops in animals
      sensitized against proteins (horse serum, etc.) and may be regarded as one of the
      manifestations of general protein hypersensitiveness, or anaphylaxis; the other
      is the tuberculin type of skin reaction which develops more slowly, leads to a
      more profound injury of the tissues and is independent of anaphylaxis as
      ordinarily conceived. 2. The tuberculin type of hypersensitiveness (as well as
      probably the typhoidin, mallein, abortin reactions, etc.) does not develop at all
      in guinea pigs sensitized with proteins, like horse serum, etc. While this form
      of hypersensitiveness may eventually be induced with materials not bacterial in
      origin, it has been observed up to date only as a reaction of bacterial
      infection. 3. Methods of treatment with protein material from bacterial cultures
      which sensitize guinea pigs to anaphylactic reactions with the bacterial
      extracts, do not sensitize them to the tuberculin type of reaction. Such
      sensitization is easily accomplished only by infecting the animals with living
      organisms. No reliable method of sensitizing guinea pigs to such reactions with
      dead bacterial material has as yet been worked out, though a few hopeful
      experiments have been obtained with massive injections of large amounts of the
      acid-precipitable substances (nucleoproteins?) from bacterial extracts. 4. In
      animals made hypersensitive to the tuberculin type of reaction by infection with
      living bacteria, the reaction may be elicited by intradermal injections of
      bacterial extracts from which all coagulable proteins, nucleoproteins, and Bence
      Jones proteins have been removed, as well as this can be done by boiling with
      acid, etc. This proteose residue alone suffices to elicit such reactions. The
      exact chemical nature of the so called proteose residue must be further studied
      and analyzed when we have had opportunity to produce bacterial extracts in large
      quantity. These points seem incontrovertible on the basis of our own experiments,
      as well as those of other workers. There thus seem to develop two definite forms
      of hypersensitiveness in guinea pigs infected with bacteria, typical anaphylaxis
      in which the protein material of the bacterial cells is concerned, which develops
      late and which can be induced by repeated injections of dead bacterial material,
      and a hypersensitiveness to non-protein constituents which differs from the
      former, both in the laws that govern sensitization and in the manifestations
      which follow injections into the sensitized animals. While there is virtual
      agreement among immunologists concerning the essential mechanism of protein
      anaphylaxis, its dependence upon an antigen-antibody reaction, and the dominating
      role played by the sessile antibodies, the mechanism of hypersensitiveness to
      tuberculin and similar bacterial substances is still a problem of much
      uncertainty. The most striking difference between the two phenomena lies, as we
      have seen, in the criteria of sensitization, in that hypersensitiveness to the
      tuberculin type of reaction can hardly ever be induced by any of the ordinary
      methods of preparation with the constituents of dead bacteria, but develops
      promptly (7 to 10 days) in the course of actual infection with living organisms.
      The considerable specificity of such reactions forces the conclusion that the
      sensitizing substance must, in some way, be derived from the infecting
      microorganisms. The idea that the failure of sensitization with dead culture
      materials is perhaps due to the elaboration in the body of infected animals of
      bacterial products not represented in extracts of test-tube cultures is rendered
      unlikely by the fact that in the tuberculin-sensitive, infected animals, we can
      produce the reactions by the application of such dead extracts. It is neither
      logical nor in keeping with biological experience to assume that one substance
      will sensitize to reaction with another. This mistake was made early in the study
      of anaphylaxis in another connection and caused considerable delay of progress.
      Krause has shown that tuberculin sensitiveness may be blunted in infected animals
      by massive, but sublethal injections of tuberculin, and we have obtained some
      indications of the same thing. Moreover, others as well as ourselves have seen
      tuberculin reactivity decline in guinea pigs and in man in the stages of very
      severe infection. These facts would eliminate any assumption of mere cumulative
      injury as explaining this type of reaction, and stamp it as a mechanism at least
      analogous to ordinary anaphylaxis. The only remaining possibility to explain the
      difference between infected animals and those treated with dead bacterial
      constituents would be to assume that the difference must lie in the manner in
      which the sensitizing substance is administered to the animals, and that
      sensitization with the proteose residue materials depends upon criteria of
      sensitization differing in regard to the time and quantity factors from those
      governing protein sensitization. If one considers the relatively simpler chemical
      structure and perhaps physically greater diffusibility of the materials concerned
      in this reaction, one might readily expect such differences in the methods needed
      for sensitization. In keeping with such a line of reasoning our experiments have
      shown that the tuberculin active materials are constantly and rapidly being
      diffused out into the culture fluid from growing organisms, in quantities greater
      than can be extracted from similar amounts of the dead bacteria. It seems
      reasonable to assume from this that the same thing may happen in the animal body
      harboring a growing focus. And it would seem quite likely that the association of
      the tuberculin type of reaction with actual infection may depend upon the fact
      that sensitization to these non-protein substances depends upon a constant steady
      absorption of large amounts of the material. Moreover, the only hopeful
      experiments on the artificial production of tuberculin sensitiveness in guinea
      pigs obtained by us were those in which massive doses of the nucleoprotein
      material injected into guinea pigs gave rise to a moderate skin sensitiveness.
      Does the so called proteose residue form antibodies, and, if so, are substances
      analogous to antibodies involved in the tuberculin type of hypersensitiveness?
      The failure to transfer passively this form of hypersensitiveness to normal
      animals with the blood and tissues of tuberculin-sensitive ones would suggest
      that no antibodies are involved. But this is not conclusive on the basis of
      available experimental facts. We are inclined to believe that antibodies of a
      sort are involved, for the following reasons: (a) In our experiments with the
      uteri of highly sensitive extract-treated guinea pigs and of tuberculous guinea
      pigs, we have occasionally had positive reactions when the proteose residue alone
      was used. (b) We believe that these proteose substances are entirely analogous to
      the substances studied by Avery and Dochez (22) in the urine and blood of typhoid
      and pneumonia patients. They obtained precipitin reactions against homologous
      immune sera with the urine of infected cases concentrated by evaporation after
      boiling with acetic acid to remove coagulable proteins. (c) Petroff, with whom we
      discussed this proteose residue early in our work, has produced it, and tells us
      that he has obtained precipitin reactions with it by titrating it against the
      serum of a sheep treated for a long time with tubercle bacillus products. In
      suggesting an antibody response to a non-protein antigen we are aware that we are
      opposing what has been regarded as a well established doctrine in immunity; this
      is justified, or at least mitigated, we believe, by the consideration that
      reactions of the antigen-antibody type are the only explanation of specificity;
      and tuberculin, mallein, and typhoidin reactions are to a considerable degree
      specific. If such reaction bodies cannot be produced by precisely the same
      methods of administration as to time and quantity which are successful in calling
      forth protein antibodies, this should not astonish us, since, after all, the
      substances that we are dealing with are simpler in chemical structure than are
      the proteins, and physically are probably of relatively greater diffusibility. It
      may be that the greater diffusibility of the proteose-like substances transfers
      much of the actual reaction phenomena to an intracellular location, and that this
      to some extent influences the presence of circulating antibodies. It may also be
      that these more diffusible non-protein antigens are more rapidly eliminated from
      the animal body than are the proteins. Indeed, the above mentioned observations
      of Avery and Dochez, and the recent work of Wildbolz (23), Lanz (24), Imhof (25),
      and Gibson and Carroll (26), who demonstrated tuberculin active antigens in the
      urine of active cases, would corroborate such a view. The evidence available at
      the present time, however, concerning antibody formation to these non-protein
      substances is, we recognize, largely indirect, at least as far as our own work is
      concerned, and we present it in the present connection purely as a working
      hypothesis. Finally, perhaps the most important theoretical consideration
      indicated by our experiments is the following. We have in the tuberculin reaction
      a form of hypersensitiveness which seems to be (in guinea pigs, at least)
      analogous entirely to the typhoidin reaction, the mallein reaction, and the
      abortin reaction. (ABSTRACT TRUNCATED)

PMID- 19868575
TI  - EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER : I. CONCURRENT INFECTIONS
      DURING THE COURSE OF EXPERIMENTAL TYPHUS FEVER IN GUINEA PIGS.
AB  - The work reported in this paper relates to the bacteria which can be cultivated
      from the blood and spleen of guinea pigs at different stages of infection with
      the virus of typhus fever. The studies show that during the period of incubation
      and before the onset of fever no ordinary bacteria appear in the cultures, while
      on the 1st day of the febrile reaction different bacteria were found in 6 of 26
      guinea pigs cultured; on the 2nd day, in 10 of 16; on the 3rd day, in 3 of 4; and
      on the 4th day in cultures of all of the 4 guinea pigs observed. The findings
      indicate that the virus of typhus fever is distinct from ordinary cultivable
      bacteria, and, as the disease set up by the virus progresses, the infected guinea
      pigs become subject to invasion by secondary or concurrent bacteria which thus
      induce a mixed infection. The bacteria which under the influence of the virus of
      typhus fever thus invade the body of the guinea pig are of several kinds, and
      vary not only among themselves, but also with the day of the fever on which the
      examination is made. Thus, on the 1st day of the fever Plotz' bacilli were
      recovered twice and anaerobic streptococci, proteus bacilli, aerobic
      diphtheroids, Gartner type bacilli, and Staphylococcus aureus each once. On the
      2nd day Plotz' bacilli were found four times, anaerobic streptococci three times,
      Gartner type bacilli, aerobic diphtheroids, Bacillus welchii, aerobic Gram
      positive diplobacilli, and Staphylococcus aureus each once. On the 3rd day Plotz'
      bacilli were recovered once, as were anaerobic streptococci and Grtner type
      bacilli. On the 4th day Staphylococcus aureus was found twice and Plotz' bacilli
      and Bacillus proteus each once. This variation in the kind of bacteria as well as
      the lack of predominance of one kind over another during the different stages of
      the febrile reaction in guinea pigs leads us to infer that they occur
      concurrently with the typhus virus. And since the more unusual of these
      organisms, the Plotz bacillus, the anaerobic streptococcus, the aerobic
      diphtheroid, and the diplobacillus are non-pathogenic for guinea pigs, while the
      more common bacteria such as the Gartner type bacillus, Welch's bacillus, the
      proteus bacillus, and the staphylococci induce distinctive effects, and since all
      the bacteria could be suppressed without their reappearance in guinea pig
      passages of the virus containing them, we believe that they are independent and
      unrelated to the true virus of typhus fever.

PMID- 19868576
TI  - EXPERIMENTAL MUMPS MENINGITIS.
AB  - It has been shown that an aseptic meningitis of 3 to 5 days duration and
      favorable prognosis can be induced in cats by intrathecal injection of sterile
      saliva filtrate from early cases of parotitis, and that such a meningitis can be
      transmitted to other cats by injecting the cerebrospinal fluid in the same
      manner. The cerebrospinal fluid does not, at any time, contain bacteria which
      grow with the ordinary culture methods.

PMID- 19868577
TI  - AN OUTBREAK OF PNEUMONIA IN DAIRY COWS ATTRIBUTED TO BACILLUS BOVISEPTICUS.
AB  - All outbreak of pneumonia in dairy cows attributed to Bacillus bovisepticus is
      described. About twenty cows and two calves were affected. The first cases were
      noted in cows purchased in Michigan. The disease next appeared in another lot of
      cows from Pennsylvania and subsequently attacked native stock. Of the ten cases
      which came under our observation, five apparently recovered, two died, and two
      severely affected cows were killed. The other case developed multiple abscesses
      of the lung and was finally killed. The more characteristic symptoms observed
      were high temperature, rapid respiration, dyspnea, cough, dullness on percussion,
      bronchial breathing, and albuminuria. The pneumonia was diffuse but first
      affected the cephalic and more dependent lobes. The process varied from hyperemia
      and hemorrhage to exudation of fibrin and leucocytes within the air spaces. The
      plugging of the interlobular lymph channels and blood vessels with fibrin was
      frequent. Bacillus bovisepticus was isolated in pure cultures from all involved
      portions of lung at autopsy. It was not found in blood cultures during the height
      of the disease, nor could it be obtained from the spleen and kidney after death.

PMID- 19868578
TI  - A STUDY OF BACILLUS BOVISEPTICUS.
AB  - It has been possible to study the cultural characters and certain of the
      immunological relationships of sixteen strains of Bacillus bovisepticus. The
      organisms have fallen into three distinct cultural groups. The largest group
      comprises eight strains, four of them obtained in pure cultures from cases of
      pneumonia in cows, two others were pure infections in calves, the others were
      associated with other organisms. This group may be characterized as short, non
      motile, Gram-negative, encapsulated rods which fail to produce indole but produce
      clear zones about the deep colonies in horse blood agar plate cultures. Members
      of this group produce acid in media containing dextrose, lactose, saccharose,
      maltose, and mannitol. The final hydrogen ion concentration in dextrose broth
      lies between pH 6.3 and 6.1. The next largest aggregation comprises six strains.
      These organisms ferment dextrose and saccharose, but do not attack lactose,
      maltose, or mannitol. All produce indole. All are soluble in ox and guinea pig
      bile but none are hemolytic. The other two strains resemble the preceding but
      attack mannitol in addition to dextrose and saccharose. They produce indole but
      are not bile-soluble. In the main the immunological relationship has been found
      to follow cultural grouping. All of Group I are agglutinated by a serum prepared
      by immunizing a rabbit with a single Group I strain. This serum fails to
      agglutinate members of other groups. The same holds true with Group II and III
      sera. In no instance has cross-agglutination between groups taken place.

PMID- 19868579
TI  - THE FACTOR DETERMINING THE SPREAD OF RED MARROW DURING ANEMIA.
AB  - Rabbits in which a chronic anemia of moderate grade is induced by repeated
      bleedings repair the hemoglobin loss much more rapidly when given subcutaneous
      injections of hemoglobin than when this is not the case. But the effect of the
      injections is not manifest for several weeks, during which many pale corpuscles
      are put out by the marrow; whence it follows that the introduced pigment does not
      find its way in quantity direct to the new-formed cells but must follow a more or
      less roundabout metabolic route, perhaps the same one as that of ordinary iron
      compounds destined for the blood. The rapid replacement of the circulating
      hemoglobin in the injected animals occurs chiefly through an increased production
      of corpuscular substance having the same color index as that found in uninjected,
      anemic controls. By color index in this connection is meant the relation of
      hemoglobin to the volume of the massed corpuscles. Late in the period of
      bleedings and hemoglobin injections the demand for stroma for the new-formed
      blood is far greater than in control animals that have been merely bled, yet the
      circulating corpuscles show no lessening in resistance to salt solution, such as
      might perhaps be expected were there a stroma lack. The hematopoietic tissue of
      the injected animals undergoes an extensive increase-a fact which speaks strongly
      for the view that the elements out of which stroma is formed are still abundant.
      The factor which determines the spread of red marrow during anemia is shown by
      our experiments to be the presence in the body of hemoglobin, or perhaps of its
      precursors, in excess of the amount which can be utilized by the marrow already
      existing. Numerous illustrations in support of the point can be adduced from
      human pathology. Two will suffice. The widespread "currant jelly" marrow of
      pernicious anemia is found in an organism rendered anemic but supplied with
      hemoglobin in excess; while the pale, restricted marrow of cases suffering from
      chronic anemia due to repeated hemorrhages is associated with depletion of the
      constituents necessary for pigment production.

PMID- 19868580
TI  - THE CAPSULES OR SHEATHS OF BACILLUS ACTINOIDES.
AB  - The production of capsules or sheaths is subject to considerable variation in
      this species. Thus far coagulated serum has been found the only substrate to
      stimulate its appearance. It is not known whether the capsular substance is
      induced by the parasitism. The presence of sheaths within epithelial cells and
      their absence in cellular exudates suggest the inference that the sheath is a
      protective substance when the parasite multiplies in living cells. The complete
      absence of sheaths in some strains might make the recognition of this species
      difficult, but if its other characters both positive and negative are kept in
      mind, this difficulty will not be serious. Next in importance to fluctuations in
      the presence or absence of capsules is the change in metabolic processes leading
      to the production and accumulation of fatty substances in the cultures. The
      original capsular material resembles in its optical characters myelins. In the
      course of artificial cultivation fat granules make their appearance at the
      expense of the original myelin-like substance. This process may be regarded as a
      degenerative one in the sense that it accompanies the gradual loss of the
      function of secreting the capsular substance.

PMID- 19868581
TI  - AGE AND MULTIPLICATION OF FIBROBLASTS.
AB  - Pure cultures of fibroblasts displayed marked differences in their activity in
      the plasma of young, middle aged, and old chickens. The rate of cell
      multiplication varied in inverse ratio to the age of the animal from which the
      plasma was taken. There was a definite relation between the age of the animal and
      the amount of new tissue produced in its plasma in a given time (Text-figs. 1 to
      10). The chart obtained by plotting the rate of cell proliferation in ordinates,
      and the age of the animal in abscissae, showed that the rate of growth decreased
      more quickly than the age increased (Text-fig. 12). The decrease in the rate of
      growth was 50 per cent during the first 3 years of life, while in the following 6
      years it was only 30 per cent. When the duration of the life of the cultures in
      the four plasmas was compared, a curve was obtained which showed about the same
      characteristics (Text-fig. 11). The duration of life of the fibroblasts in vitro
      varied in inverse ratio to the age of the animal, and decreased more quickly than
      the age increased. As the differences in the amount of new tissue produced in the
      plasma of young, middle aged, and old chickens were large, the growth of a pure
      culture of fibroblasts could be employed as a reagent for detecting certain
      changes occurring in the plasma under the influence of age. But the method
      possesses the necessary accuracy only when it is used as has already been
      described, and by technicians thoroughly trained in the details of its
      application. A comparative study of the growth of fibroblasts in media containing
      no serum, and serum under low and high concentrations, was made in order to
      ascertain whether the decreasing rate of cell multiplication was due to the loss
      of an accelerating factor, or to the increase See PDF for Structure of an
      inhibiting one. In high and low concentrations of the serum of young animals, no
      difference in the rate of multiplication of fibroblasts was observed. This showed
      that the serum of an actively growing animal did not contain any accelerating
      agent. The same experiments were repeated with the serum of a 3 year old and a 9
      year old chicken. The medium made of a high concentration of serum had a markedly
      depressing effect on the growth, and this effect was greater in the serum of the
      older animal (Text-fig. 13). The results of the experiments showed in a very
      definite manner that certain changes occurring in the serum during the course of
      life can be detected by modifications in the rate of growth of pure cultures of
      fibroblasts, and that these changes are characterized by the increase of an
      inhibiting factor, and not by the loss of an accelerating one. It appeared,
      therefore,that the substances which greatly accelerate the multiplication of
      fibroblasts and are found in the tissues do not exist in the blood serum, or are
      constantly shielded by more active inhibiting factors. The curve which expresses
      the variations of the inhibiting factor in function of the age was compared with
      that showing the variations of the rate of healing of a wound according to the
      age of the subject. For wounds of equal size, the index of cicatrization, which
      expresses the rate of healing, varies in inverse ratio to the age. The different
      values of the index of cicatrization of a wound 40 sq. cm. in area, taken from
      measurements made by du Nouy, were plotted in ordinates, and the age of the
      subject in abscissae (Text-fig. 14). The curve showed a decrease in the activity
      of cicatrization which resembled the decrease in the rate of growth of
      fibroblasts in function of the age of the animal. This suggested the existence of
      a relation between the factors determining both phenomena.

PMID- 19868582
TI  - STUDIES ON ENDOTHELIAL REACTIONS : V. THE ENDOTHELIUM IN THE HEALING OF ASEPTIC
      WOUNDS IN THE OMENTUM OF RABBITS.
AB  - THE FOLLOWING HYPOTHESIS MAY BE DEDUCED FROM THE EVIDENCE JUST SUBMITTED: The
      endothelium of the end capillaries, the fibroblast, and the immediate derivatives
      of these two are all mesenchymal in origin. Injury produces a reaction wherein
      there is stasis and hemorrhage, with the exudation of cells and fluids that
      contain some element or elements that affect these mesenchymal derivatives in
      such a way as to reestablish their embryonal characteristics. As a result, they
      form a local, temporary mesenchyma at the site of injury, proliferate, migrate,
      and differentiate according to the needs of the case until the injury is
      repaired. They may form connective tissue, phagocytes, polyblasts, new vessels,
      etc. Phagocytosis and absorption gradually withdraw the exciting agents from the
      seat of injury, the temporary mesenchyma returns to adult type, and all that
      remains is the products of the process that are necessary for scar formation. It
      is apparently erroneous to think of the mononuclear cells of young granulation
      tissue as fibroblasts, endotheliocytes, etc., they should be considered as
      representing various stages in the differentiation of a local mesenchyma until
      the process of healing is completed, when they return to the adult types
      represented by these more specific names. The term polyblast, originated by
      Maximow, is particularly applicable to these cells, for under the conditions they
      are truely polyblastic; but that they are derived from lymphocytes is not
      indicated by results of this experiment-the lymphocytes and plasma cells appear
      to play a part that is unconnected with the formation of new tissue. No definite
      statement can be made as to the nature of the stimulating substance, or
      substances, that bring about this reversion to embryonal type. As indicated, they
      are associated in some way with the blood, for the most marked cellular
      metaplasia is noted in connection with areas of hemorrhage, or in proximity to
      vascular areas. That the exciting substances are contained in the erythrocytes is
      furthermore indicated by the fact that the most metaplastic areas are found where
      the mesenchymoid cells are growing among masses of red corpuscles, with little
      visible fluid or fibrin present (cf. Fig. 24). Whether these substances are
      enzymes or not is purely problematical. There is very little, in the several
      hundred sections studied for this and later papers, to indicate that wound
      healing is an orderly procession of specific cells to designated positions in
      these wounds. The only tissues retaining their continuity in growth to a degree
      in any way comparable with the descriptions in some text-books, are the surface
      epithelium and the vascular buds, or branches. The majority of mononuclear cells
      of mesenchymal type appear to fill in the injured area by migration, rather than
      by growth in continuity. Once they have reached a certain point, they react in
      the various ways just described. There is, of course, a migration of
      differentiated cells, such as macrophages, polymorphonuclears, lymphocytes, etc.,
      from the healthy tissue; but the framework, or structural foundation, of the
      granulation tissue appears to be composed of the practically undifferentiated
      derivatives of the connective tissue and capillary endothelium. In other words,
      it is conceivable that cells originating from connective tissue might become
      phagocytes and vice versa, both types temporarily losing all specificity under
      the influence of some chemical or enzymatic excitant in the exudate. Until we
      understand the physiology and chemistry that determine the developmental and
      retrograde changes of the normal, embryonal mesenchyma, as well as those of this
      temporary mesenchyma, we can never fully comprehend wound healing.

PMID- 19868583
TI  - STUDIES ON THE TREATMENT OF HUMAN TRYPANOSOMIASIS WITH TRYPARSAMIDE (THE SODIUM
      SALT OF N-PHENYLGLYCINEAMIDE-p-ARSONIC ACID).
AB  - The present study of the action of tryparsamide in human trypanosomiasis
      concludes a series of chemical and biological investigations in a particular
      problem of chemotherapy and thus represents the final step in a logical method of
      approach to such a problem. It has been shown that tryparsamide, the sodium salt
      of N-phenylglycineamide-p-arsonic acid, possesses a marked trypanocidal activity
      in human trypanosomiasis caused by Tr. gambiense. Single doses of from 0.5 to 5.0
      gm. produced a peripheral sterilization of lymph glands and blood in an average
      of 6 to 12 hours. The duration of the peripheral sterilization following single
      doses of 17 to 83 mg. per kilo ranged from 17 to 58 days in patients who
      ultimately showed a return of trypanosomes to the peripheral blood. In a number
      of patients, however, treated with single doses of 9 to 68 mg. per kilo, no such
      relapse was detected during an observation period of from 40 to 111 days. The
      drug is extremely soluble in water and may be administered intramuscularly as
      well as intravenously. The immediate trypanocidal action after intramuscular
      administration was as rapid as that following the intravenous route while the
      duration of peripheral sterilization was appreciably longer. Relatively few
      repeated doses produced in advanced cases a marked and rapid diminution of the
      cells of the spinal fluid and were associated with definite improvement of mental
      and nervous symptoms. The occurrence of visual disturbances in certain advanced
      cases was the only untoward effect detected during the course of the work, and
      was apparently related to a too frequent administration of the drug. The
      condition was transitory in the majority of instances and resumption of treatment
      was not followed by a recurrence of this symptom. The general beneficial effect
      of the drug was a noticeable feature of its action in both early and advanced
      cases as shown by the disappearance of subjective symptoms, by the return of the
      pulse and temperature to normal limits, by the pronounced improvement of the
      blood picture, and by well marked gains in weight.

PMID- 19868584
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      VI. IMMUNITY REACTIONS.
AB  - The experiments described furnish additional evidence of the pathogenic character
      and the virtual identity of the various strains of the active agent derived from
      the nasopharyngeal secretions of influenzal patients with which the transmission
      experiments in rabbits have been carried out. The active material has been shown
      to be of antigenic nature, so that rabbits are protected from the effects of a
      second inoculation. The experiments indicate also the antigenic identity of the
      various strains of the active agent with each other and with Bacterium
      pneumosintes. Finally, the experiments show that the protection may persist for
      14 months which is the longest period yet tested.

PMID- 19868585
TI  - HETEROGENIC SERUM, AGE, AND MULTIPLICATION OF FIBROBLASTS.
AB  - The presence in a culture medium of heterogenic serum of various concentrations
      exerts a definite influence on the rate of multiplication of fibroblasts. Dog
      serum does not inhibit the growth of See PDF for Structure chicken fibroblasts
      markedly until its concentration reaches 15 per cent. Beyond this figure, each
      increase of the concentration brings about a rapid decrease in the rate of cell
      multiplication. When the concentration reaches from 30 to 45 per cent, no growth
      takes place. The inhibiting action of cat serum begins to manifest itself at a
      concentration of 25 per cent and prevents cell proliferation completely at a
      concentration of 55 and 60 per cent. The ratio, See PDF for Equation can be taken
      as expressing the action of the serum on fibroblast multiplication; that is, as
      the growth index of the serum. See PDF for Structure The inhibiting influence of
      heterogenic serum was found to vary in direct ratio to the age of the animal from
      which it was obtained. The rate of proliferation of chicken fibroblasts was
      studied comparatively in media containing varied concentrations of serum from
      young and old animals. For each concentration of serum, the rate of growth in the
      serum of the old animal was expressed in relation to the rate of growth in the
      serum of the young animal. When cat serum was used, the curve obtained in
      plotting this ratio in ordinates and the serum concentration in abscissae showed
      a rapid increase in the inhibiting action of the old serum as soon as the
      concentration reached 30 per cent. The same tests were repeated with the serum
      from young and old dogs. The general results were identical, although See PDF for
      Structure the quantitative inhibiting action of both sera was greater than that
      of cat serum. It may be concluded that under the conditions of the experiments:
      1. Heterogenicsera inhibit and prevent the growth of chicken fibroblasts when
      their concentration is made to vary within certain limits. 2. A relation exists
      between the rate of growth of chicken fibroblasts, the concentration of the
      heterogenic serum, and the age of the animal from which the serum is taken. Thus,
      the rate of proliferation of chicken fibroblasts expressed by the growth index of
      the serum can be used as a means for detecting certain changes brought about by
      age in a heterogenic serum.

PMID- 19868586
TI  - A STUDY OF THE RELATION OF TREPONEMA PALLIDUM TO LYMPHOID TISSUES IN EXPERIMENTAL
      SYPHILIS.
AB  - A widespread dissemination of Treponema pallidum from a local focus of
      inoculation in the rabbit constantly occurs by way of the lymphatics. Spirochetes
      were regularly recovered from the satellite lymph nodes by animal inoculation
      after scrotal inoculation; they were present as early as 2 days, when no specific
      primary reaction was detected, and at later periods of from 5 to 61 days after
      inoculation. Other superficial nodes at remote sites such as the popliteals and
      with no syphilitic lesions in the drainage area have also been shown to harbor
      active organisms. Although spirochetes were found in relatively few of the lymph
      node emulsions, the orchitis resulting from their injection was of a rapidly
      progressive type with an incubation period but slightly longer than that produced
      by a testicular or skin nodule emulsion rich in spirochetes. It has further been
      shown that a syphilitic infection is sufficiently established in the rabbit body
      within 48 hours after scrotal inoculation so that the primary lesion is no longer
      essential for its maintenance. Active treponemata survive in the popliteal lymph
      nodes for long periods of time and have been regularly recovered from them in
      cases of true latency. The lymph nodes, therefore, function as reservoirs of the
      organisms. The ability to recover the spirochetes from lymphoid tissue through
      successive generations is seen in the serial passage of lymph node emulsion to
      testicle during an 18 months period. The persistence of spirochetes in lymphoid
      tissue irrespective of the presence or absence of syphilitic lesions is a
      characteristic and fundamental feature of syphilis of the rabbit. The existence
      of infection, therefore, may be demonstrated at any time by the recovery of
      spirochetes from the popliteal lymph nodes by animal inoculation. This fact is of
      great practical importance in the therapy of the infection and may be profitably
      utilized in determining the ultimate effect of a therapeutic agent. These
      experiments demonstrate that the disease is not confined to the site of local
      inoculation but that lymphogenous dissemination of treponemata regularly takes
      place, and that during the course of this process organisms become localized in
      the lymph nodes and exist there indefinitely irrespective of the occurrence of
      manifestations of disease. The intimate relation of Treponema pallidum to
      lymphoid tissue is an essential concept of syphilis of the rabbit, and from this
      point of view, the infection is primarily one of lymphoid tissue.

PMID- 19868587
TI  - STUDIES ON AGGLUTINATION WITH THE AID OF THE CENTRIFUGE. THE INFLUENCE OF
      TEMPERATURE ON ABSORPTION AND FLOCCULATION.
AB  - The flocculation of bacteria which have absorbed specific agglutinins may be
      mechanically effected by means of the centrifuge, with results that coincide with
      those obtained by the standard method of test. Specific serological differences
      between meningococci, for example, may be determined by the centrifuge method.
      The technique is described. By the elimination of the inconstant time factor in
      the flocculation phase opportunity is given for a closer analysis of specific
      absorption, and of the influence of various conditions upon both phases of
      agglutination. The velocity of the absorption reaction is a function of the
      temperature at which it occurs, and the acceleration with increasing temperature
      is of the order of chemical phenomena. The absorption reaction proceeds most
      rapidly near the temperature of antibody destruction. The injurious effect of
      high temperature is revealed first in the serum; the antigen-antibody complex is
      not less sensitive. The flocculation phase is also promoted by higher
      temperature, but lags far behind absorption, and consumes most of the time
      required for spontaneous agglutination. The presence of an excess of antibodies
      greatly accelerates absorption and flocculation. The absorption reaction, under
      such circumstances, is ordinarily completed within a relatively short time.

PMID- 19868588
TI  - THE FREQUENCY OF BACILLUS INFLUENZAE IN THE NOSE AND THROAT IN ACUTE LOBAR
      PNEUMONIA.
AB  - 1. Bacillus influenza is frequently found in association with lobar pneumonia. 2.
      In lobar pneumonia both Bacillus influenza and pneumococcus are frequently found
      in the nose. 3. The influenza bacilli found in the upper respiratory tract of
      cases of lobar pneumonia are of various types. 4. The exact significance of these
      findings is at the present time not clear.

PMID- 19868589
TI  - THE EFFECT OF PULMONARY CONGESTION ON THE ON THE VENTILATION OF THE LUNGS.
AB  - 1. A method is described for producing pulmonary congestion, together with what
      may be termed a differential spirometer method for studying lung ventilation. 2.
      The method utilized permits an approximately accurate prediction of degrees of
      pulmonary edema in the living animal, and suggests avenues of approach for the
      very difficult problems of pulmonary capillary pressure. 3. It is shown that
      intravascular blood can encroach markedly upon the pulmonary air space. Although
      the methods used in these animal experiments do not resemble vital capacity
      measurements in man, their result is so definite that their applicability to
      clinical conditions may be considered. 4. The similarity between the experiments
      described and certain conditions of cardiac decompensation, of which mitral
      stenosis is the best example, is pointed out.

PMID- 19868590
TI  - EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER : II. SURVIVAL OF THE VIRUS
      IN AEROBIC AND ANAEROBIC CULTURE MEDIA.
AB  - The results of the foregoing experiments show that the typhus virus, found in the
      blood of guinea pigs during the height of typical experimental typhus fever, does
      not survive at 37 degrees C. in anaerobic media for as long a period as in the
      same media under aerobic conditions. In media from which oxygen is excluded, the
      viability period is 24 to 48 hours; in the same media having no barrier to
      atmospheric oxygen, the period is usually 5 days, in one instance, 3 days. The
      dead virus fails to induce not only the typical experimental disease but also an
      immunity to further injections of typhus virus. That the death of the virus is
      due to exclusion of oxygen from the medium, rather than to a change in the
      hydrogen ion concentration therein is inferred from the fact that media with
      varying hydrogen ion concentrations, such as broth (pH 7.4), horse serum (pH
      7.8), and human ascitic fluid (pH 8.0) have the same comparative effect on the
      virus, when under aerobic and anaerobic conditions. That is, in all, the
      anaerobic state causes a shortening of the viability period of the typhus virus.
      In the Smith-Noguchi tissue, ascitic fluid, sealed medium in which bacteria
      resembling Plotz' bacilli grow luxuriantly and remain viable for several weeks,
      the typhus virus does not increase in virulence, and even dies after 24 hours.
      This evidence supports the conclusion previously presented that the Bacillus
      typhi exanthematici of Plotz is not identical with the active agent of typhus
      virus.

PMID- 19868591
TI  - EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER : III. FILTRATION
      EXPERIMENTS.
AB  - We have presented experiments to show that the typhus virus in the tissues of the
      guinea pig during the height of reaction to the experimental disease does not
      lose its infecting power when the cells of the brain or of the spleen are
      disintegrated by repeated freezing and thawing, or by freezing and desiccating,
      or by crushing by mechanical means, or by grinding into a homogeneous pulp with
      sand. The virus after such treatment is as actively infective as in the same
      tissue not subjected to the disintegrating influences. The possibility exists,
      therefore, of an extracellular condition of the typhus virus. Fourteen attempts
      to filter through Berkefeld V and N candles the virus contained in the
      disintegrated tissue have all resulted in failure.

PMID- 19868592
TI  - DO SPECIES LACKING A GALL BLADDER POSSESS ITS FUNCTIONAL EQUIVALENT?
AB  - In a previous paper the point has been brought out that the influence of the gall
      bladder upon the bile differs entirely from that of the ducts, the one organ
      acting to concentrate the secretion markedly and the other to dilute it slightly.
      The question arises, in species lacking a gall bladder, whether the concentrating
      function of this organ will be found lodged in the ducts. To test the point,
      observations have been made upon the mouse and rat, since these animals though so
      nearly related have, the mouse, a gall bladder and the rat, none. The normal bile
      was first studied. Both animals were found to secrete larger quantities than do
      cats and dogs, but less than the guinea pig and rabbit. Methods were worked out
      for the quantitation of the pigment which was used as the index to changes in
      concentration. Bladder bile of the mouse was regularly found to be more
      concentrated than that collected from the common duct of the same animal. The
      bile collecting during stasis regularly showed a great increase in pigment
      content, such as in other species is brought about by the action of the gall
      bladder. In the rat, on the other hand, stasis bile never became more
      concentrated in pigment than the normal. The gall bladder, then, is not only
      absent from the rat in form, but in one at least of its important functions. That
      its other obvious function-that of a reservoir-cannot be assumed in the rat by
      the ducts would seem to be indicated, not only by the small size of these
      channels, but by the recent observation of Mann that the tonus of the sphincter
      of Oddi is almost negligible in the rat, in contradistinction to animals which
      possess a gall bladder. It is an interesting fact that the bile of the rat, which
      as has been said, undergoes no condensation of bulk after leaving the liver,
      contains on the average eight times as much pigment as does the liver bile of the
      mouse which is submitted to concentration. Whether it is correspondingly strong
      in substances useful for digestion, and therefore ab initio requires no
      concentration, is a matter upon which little can be said at present. However, in
      this connection the fact that the bulk of bile secreted per gram of liver weight
      is identical in both animals may be significant. Although this output is the
      same, the mouse liver when compared with the body weight (1 to 14.6) is
      relatively larger than that of the rat (1 to 21.7), so that the mouse secretes
      somewhat more bile per 100 gm. of body weight. This bile as it comes from the
      liver is but one-eighth as strong at least in pigment as rat bile, but the
      concentrating activity of the gall bladder is so great that the products yielded
      to the intestine may become not dissimilar.

PMID- 19868593
TI  - SOURCES OF THE ANTIBODIES DEVELOPING AFTER REPEATED TRANSFUSION.
AB  - The massive agglutination observable in the shed blood of transfused rabbits, and
      associated not infrequently with sudden marked blood destruction, has a practical
      significance in connection with the untoward results of repeated transfusion from
      donors originally compatible; and it has special theoretical interest because the
      clumping of the cells is apparently an autoagglutination. To determine the actual
      source of the antibodies has been the object of the present work. The
      agglutination in its most marked form has been traced to isoantibodies elicited
      by the presence in the body of corpuscles originally found compatible; and the
      frequently associated, rapid blood destruction is doubtless of similar origin.
      Occasionally antibodies develop in the donor bloods during the period of
      transfusion, but they are so weak as to be negligible. There remain instances of
      what would seem to be true autoagglutination due to serum bodies induced by the
      transfusions as a by-product, so to speak, in the manufacture of isoagglutinins.
      The antigenic relationship between the red cells of different rabbits is so close
      that normal isoagglutinins became fixed in the cold upon their elaborator's own
      corpuscles. Agglutinins exist within the red cells of rabbits-as has been claimed
      by Klein. They are readily demonstrable in watery extracts of the dried
      corpuscles. Whether similar agglutinins ever exist within human cells remains to
      be determined. We have not found them in the normal corpuscles.

PMID- 19868594
TI  - STUDIES ON THE PNEUMONIC EXUDATE : V. THE RELATION OF PNEUMONIC LUNG PROTEASE
      ACTIVITY TO HYDROGEN ION CONCENTRATION, AND A CONSIDERATION OF THE ORIGIN OF THE
      ENZYME.
AB  - 1. Washed cellular suspensions of pneumonic lungs, previously preserved with
      chloroform and toluene, contain a protease or proteolytic ferment, derived
      chiefly from the leucocytes of the exudate. 2. This protease is able to convert
      horse fibrin to a non-coagulable split product. In a pH range of 4.0 to 8.0 the
      digestion is slight at the most acid end. With decrease in acidity there is a
      gradual rise in activity to pH 6.0, and then a sharp increase up to the maximum
      digestion at pH 8.0. Judging from the amino nitrogen determinations, the most
      complete splitting occurs at pH 7.0. The degree of autolysis occurring in the
      pneumonic lung cellular suspension controls suggests that the active enzyme is
      identical with that causing the digestion of the fibrin. 3. Washed cellular
      suspensions of normal lungs, previously preserved with chloroform and toluene,
      contain a proteolytic enzyme which is active in a moderately acid medium (pH 4.0)
      and essentially inactive in less acid, neutral, and slightly alkaline media.

PMID- 19868595
TI  - THE TRANSMISSION OF AGGLUTININS OF BACILLUS ABORTUS FROM COW TO CALF IN THE
      COLOSTRUM.
AB  - The agglutinins towards Bacillus abortus found in the blood serum of new-born
      calves are obtained from the mother through the colostrum. Calves at birth,
      unfed, are without agglutinins. The problem of the production of agglutinins by
      the fetus in whose tissues Bacillus abortus has multiplied and which is
      subsequently expelled prematurely is not touched by these observations.

PMID- 19868596
TI  - THE ERYTHROPOIETIC ACTION OF GERMANIUM DIOXIDE.
AB  - Injections were made of a sterile 0.4 per cent solution of germanium dioxide into
      four lots of mature male and female albino rats. Exact conditions of control were
      maintained. To two lots there was administered in four doses at intervals of 4
      days a total of 6.6 mg. of the oxide per kilo of body weight. To two lots there
      was given in three doses at like intervals a total of 45 mg. of the compound per
      kilo of body weight. In each lot there was one rat which served as a control and
      which did not receive any germanium. A preliminary period of observation was
      maintained as a further control during which two determinations of the
      erythrocyte and leucocyte counts of the blood were made 7 days apart on all the
      rats. Weekly counts were made on all the rats during the progress of the
      investigation which lasted for 4 weeks, during 3 of which the treated animals
      were under the influence of germanium. In the first group 11 days elapsed between
      the last injection and the last count. In the second group the interval was 14
      days. It was found that without exception all of the test rats responded to the
      germanium dioxide by a marked and sustained rise in the number of erythrocytes in
      the blood which ranged from 1 to nearly 5 millions. These results are
      statistically valid. There was an apparent tendency for the degree of effect to
      be related to the initial erythrocyte number, in that with a lower initial count
      there seemed to take place a greater rise, and vice versa. There was no
      indication that the larger doses of germanium dioxide exerted a greater
      stimulating effect on the production of the resultant erythrocythemia than the
      smaller doses. There is evidence that the effect is quick in making its
      appearance. The rise in the red cell count was found to occur within a week, and
      after but two injections of the oxide. Indications were obtained that germanium
      dioxide tends to increase the coagulability of the blood. Autopsy findings showed
      color changes in the liver and bone marrow. We believe that germanium dioxide is
      an erythrocytogenic agent and we hope that fruitful results will come from its
      therapeutic application.

PMID- 19868597
TI  - THE USE OF PHENOL RED AND BROM-CRESOL PURPLE AS INDICATORS IN THE BACTERIOLOGICAL
      EXAMINATION OF STOOLS.
AB  - 1. Either phenol red or brom-cresol purple may be used as indicators in the
      preparation of lactose agar plates for the isolation of members of the typhoid
      dysentery group of bacteria from stools. Of the two, brom-cresol purple gives
      sharper differentiation and is to be preferred. 2. These indicators exercise no
      restraining influence upon the growth of cultures of the typhoid bacillus or
      paratyphoid bacillus freshly isolated from the human body, or of laboratory
      cultures of Bacillus dysenteria. 3. Both indicators may be successfully employed
      with brilliant green in the isolation of the typhoid-paratyphoid group from
      stools without sacrificing the restraining activity of the brilliant green upon
      other bacteria.

PMID- 19868598
TI  - ROENTGEN RAY INTOXICATION : I. UNIT DOSE OVER THORAX NEGATIVE-OVER ABDOMEN
      LETHAL. EPITHELIUM OF SMALL INTESTINE SENSITIVE TO X-RAYS.
AB  - Roentgen radiation of the thorax (abdomen shielded) in dogs, even with large
      doses (up to 512 milliampere minutes), gives no clinical evidence of
      intoxication. There may be a transient leucopenia and a slight rise in urinary
      nitrogen. Roentgen radiation of the abdomen (thorax shielded) in dogs, with a
      dose of 350 milliampere minutes, will almost certainly cause a fatal
      intoxication. Smaller doses may be survived but usually with signs of
      gastrointestinal intoxication. This lethal intoxication due to abdominal
      radiation presents a remarkably uniform clinical and anatomical picture. There is
      a latent period of 24 to 36 hours, during which the dog is perfectly normal
      clinically. The 2nd day usually shows the beginning of diarrhea and perhaps some
      vomitus. The 3rd and 4th days show progressive intoxication with increasing
      vomiting and bloody diarrhea until the dog becomes stuporous. Death is almost
      always on the 4th day. Anatomically the only lesions of significance are to be
      found in the small intestine. The epithelium of the crypts and villi shows more
      or less complete necrosis, and this condition may involve almost all of the small
      intestine. The epithelium may vanish completely except for a few cells here and
      there which have escaped and are often found in mitosis, probably an effort at
      repair and regeneration. We are forced to the conclusion that this remarkable
      injury of the epithelium of the small intestine is responsible for the various
      abnormal reactions and final lethal intoxication which follow a unit dose of
      Roentgen radiation over the abdomen of a normal dog. This sensitiveness of the
      intestinal epithelium to x-rays is not appreciated and should be given proper
      consideration in clinical work.

PMID- 19868599
TI  - ROENTGEN RAY INTOXICATION : II. A STUDY OF THE SEQUENCE OF CLINICAL, ANATOMICAL,
      AND HISTOLOGICAL CHANGES FOLLOWING A UNIT DOSE OF X-RAYS.
AB  - Roentgen radiation in lethal dosage, given over the abdomen of a normal dog, is
      followed by a physiological reaction of remarkable uniformity. The first 24 hour
      period following the exposure is negative clinically and anatomically, but
      histologically we see frank changes in the bone marrow, spleen, lymph glands, and
      ovaries. There are definite nuclear changes with degeneration in the crypt
      epithelium of the small intestine. The second 24 hour period shows slight
      clinical disturbances of gastrointestinal nature (vomitus and diarrhea). The
      mucosa of the small intestine shows scattered ecchymoses, but the histology of
      the small intestine is important. The necrosis of the crypt epithelium may be
      almost complete, while the epithelium of the villi remains practically intact.
      There are a little edema and invasion of wandering cells. The third 24 hour
      period shows increasing clinical disturbance with vomiting and bloody diarrhea.
      Anatomically the small intestine from the edge of the pylorus to the rim of the
      ileocecal valve looks raw, red, and inflamed. The crypt and villous epithelium
      has in large part vanished, leaving a collapsed framework of the mucosa showing a
      little edema and invasion of wandering cells. The 4th day marks the peak of the
      intoxication, and death usually takes place at this time, preceded by coma.
      Anatomically and histologically the picture is like that of the 3rd day. There is
      more evidence of mitosis and efforts of repair on the part of the intestinal
      epithelium. The stomach is not concerned in this reaction, but the colon may show
      evidences of a slight injury. The colon is obviously much more resistant than is
      the small intestine. We believe the evidence is conclusive that the injury done
      the epithelium of the small intestine is wholly responsible for the stormy
      clinical picture and fatal intoxication.

PMID- 19868600
TI  - ROENTGEN RAY INTOXICATION : III. SPEED OF AUTOLYSIS OF VARIOUS BODY TISSUES AFTER
      LETHAL X-RAY EXPOSURES. THE REMARKABLE DISTURBANCE IN THE EPITHELIUM OF THE SMALL
      INTESTINE.
AB  - Exposure to large doses of x-rays will cause notable increase in the speed of
      autolysis of the crypt or secretory epithelium of the dog's small intestine.
      These changes can be demonstrated readily in material obtained from dogs killed
      2, 24, 48, 72, or 96 hours after the initial radiation (Text-figs. 1 and 2). In
      the radiated dogs the secretory crypt epithelium of the small intestine autolyzes
      first and the epithelium of the villi last, while the reverse is true in the
      normal control small intestine. These abnormalities of autolysis associated with
      lethal Roentgen ray exposures can be demonstrated for the small intestine over
      the whole 4 day period subsequent to radiation. The colon shows little change and
      the stomach no demonstrable changes in autolysis under like conditions. The
      kidney likewise is negative. The spleen, lymph glands, liver, and pancreas show a
      moderate increase in speed of autolysis in tissues taken from radiated animals
      within 48 hours of the initial exposure. What the significance of this
      disturbance of cell ferments in the intestinal mucosa may be, we cannot pretend
      to say. At least these observations strengthen one's confidence in the profound
      functional disturbance of this important intestinal epithelium-a disturbance
      which we believe is responsible for the clinical abnormalities and fatal
      intoxication.

PMID- 19868601
TI  - A STUDY OF RENAL FUNCTION IN ROENTGEN RAY INTOXICATION : RESISTANCE OF RENAL
      EPITHELIUM TO DIRECT RADIATION.
AB  - Our experiments give no support to the current belief that an x-ray nephritis may
      be produced by direct or indirect action of the hard Roentgen rays. Moderate
      doses of x-rays given repeatedly over considerable periods of time have no
      demonstrable influence on renal function or renal structure. With x-ray exposures
      of the abdomen and shielding of the kidneys fatal intoxication may be produced
      without the slightest disturbance of kidney function as measured by the ability
      of the kidney to eliminate phenolphthalein and urea. Large doses of the x-rays
      given directly over the kidney may cause a slight but distinct lowering of renal
      function which lasts for a period of a few days. We have been unable to recognize
      any corresponding histological change. We feel that the usual therapeutic doses
      of the x-rays can be given over the kidneys without apprehension. The renal
      tissue is much more resistant to x-rays than is the epithelium of the small
      intestine.

PMID- 19868602
TI  - THE RELATION OF THE HYPOPHYSIS TO ANTIBODY PRODUCTION.
AB  - An operative technique was evolved permitting successful partial hypophysectomy
      in guinea pigs. Such animals, when immunized to Bacillus typhosus, produced
      specific agglutinins in the same quantity and at the same rate as unoperated and
      operation controls immunized at the same time and by the same method. In guinea
      pigs previously immunized to Bacillus typhosus and hen red blood corpuscles
      partial hypophysectomy had no effect on the continued production and persistence
      of typhoid agglutinins, hemagglutinins, and hemolysins. In guinea pigs immunized
      to Bacillus typhosus both the continued ingestion and the intraperitoneal
      injection of the whole pituitary gland extract (Burroughs Wellcome) had no effect
      on the subsepuent agglutinin titers as compared to that of normal animals. The
      experiments would appear to show either that the hypophysis does not play an
      important direct or indirect part in the production of and persistence in the
      blood of typhoid agglutinins, hemagglutinins, and hemolysins, or that the amount
      of hypophysis left behind in the operation in order to maintain life is adequate
      also to exercise the degree of functional influence on these processes which the
      entire hypophysis conceivably exercises.

PMID- 19868603
TI  - STUDIES UPON EXPERIMENTAL MEASLES : I. THE EFFECTS OF THE VIRUS OF MEASLES UPON
      THE GUINEA PIG.
AB  - In general it may be said that three striking alterations occurred constantly in
      the animals reacting to intracardiac injections of blood from cases of measles;
      namely, pyrexia, leucopenia, and nephritis. The elevation in temperature usually
      began about the 9th day following inoculation, the rise being fairly abrupt from
      the normal to 104 degrees F. and above, at which height it remained with slight
      fluctuations for 3 or 4 days, finally subsiding by lysis. During the period of
      fever, particularly in the animals of first transmission, often no objective
      signs of illness were to be noted, the guinea pigs remaining lively and eating as
      usual. When the animals showed any outward signs these were manifested by a loss
      of appetite, lusterless and ruffled hair, and indisposition to move even when
      disturbed. The typical exanthematous signs of human measles were not observed in
      any of the animals. In some there occurred a slight coryza and watering at the
      eyes; however, no special account was attached to these signs as they were rather
      indefinite and inconstant, especially for animals of first transmission.
      Coincident with the rise of temperature there always appeared a fall in the total
      leucocytic count; in some animals the drop in white cells preceded the rise in
      temperature by 2 to 3 days. The leucopenia, though well defined, varied for
      animals of the same series. In some the count was as low as 3,600 cells per c.
      mm.; in no case did we fail to note at least a moderate fall in the leucocytes.
      The average time for the appearance of this cellular change was 9 to 10 days
      following inoculation; in other words, the leucocytic reaction seemed to indicate
      the end of the incubation period. So constant and striking was the leucopenia
      that we stress this as the most significant feature of the reaction of the guinea
      pig to the injection of measles blood, particularly since normal blood produced
      not the slightest change in these white elements. The greatest leucocytic
      depression was observed around the 12th to 14th days, which corresponded
      approximately to the stage of temperature peak. Following the leucopenia, the
      leucocytic rise was very gradual, taking on the average 8 days to attain the
      normal level. The animals killed at the height of the reaction, or those dying
      presumably from the effects of the blood containing virus, showed as the most
      constant lesion gross evidences of acute nephritis. The kidneys in these cases
      were swollen, cloudy, and congested. In certain guinea pigs there were in
      addition well defined petechiae and larger blood extravasations scattered
      throughout the cortical substance. In the animals dying after inoculation, the
      kidney alterations were found so constant and characteristic that we regarded
      them as a special index of the experimental infection. In these animals the
      hemorrhagic areas were not infrequently 2 to 5 mm. in extent, and when occurring
      on the surface of the organ produced a separation of the capsule. Occasionally
      free blood was noted in the pelvis, and in the absence of hemorrhage within the
      pelvic lining, we assumed that it came from the uriniferous orifices of the
      calicos. Microscopically the kidney sections revealed evidence of acute
      hemorrhagic nephritis, the hemorrhages for the most part being related to the
      capillaries of the tufts and the tubules of the pyramids. In the most pronounced
      cases practically all glomeruli were affected. Every stage from marked dilatation
      of the capillary whirl to well defined intercapillary blood extravasations that
      often filled the capsular space, and in consequence partially or completely
      obliterated the glomeruli, were found. Whether a destruction of the endothelium
      occurred, could not be determined. The absence of a neutrophilic reaction was of
      special significance, these elements of acute inflammation being nowhere found
      associated with the kidney lesion. The blood in relation to the tubules commonly
      occurred in the lumen of the collecting tubules and in the form of red blood cell
      casts. The spleen usually was found enlarged, particularly in the guinea pigs
      presumably dying as a result of the virus injections. Aside from the usual
      parenchymatous changes common to toxemias, the other internal organs showed
      nothing of special note.

PMID- 19868604
TI  - HEMOLYSIS OF ERYTHROCYTES IN CONTACT WITH GLASS.
AB  - 1. Washed erythrocytes, in both acid and alkaline solutions, hemolyze more
      rapidly when allowed to settle out on a clean microscope slide than when kept in
      suspension. 2. This is also true on slides coated with paraffin, paraffin oil, or
      vaseline, and on mica surfaces. 3. The presence of as little as 0.1 per cent
      serum inhibits such contact hemolysis, particularly in alkaline solutions. 4.
      Contact hemolysis is most marked on slightly soiled glass, and may occur so
      rapidly with unfixed cells in a hemocytometer that accurate counts are rendered
      impossible. 5. Erythrocytes are more sticky than normally in acid solutions and
      less sticky in alkaline solutions. 6. The increased stickiness of erythrocytes in
      acid solutions and their larger size during contact hemolysis in acid media
      provide some experimental evidence for the view that contact hemolysis is to be
      correlated with an attempt on the part of the corpuscles, or some ingredient of
      the corpuscle, to spread on the glass after the manner of leucocytes and
      invertebrate blood cells.

PMID- 19868605
TI  - EXPERIMENTAL GENERALIZED ANALGESIA AFTER EXPOSURE TO SOME WAR GASES.
AB  - Cats gassed with dimethylsulfate or chloropicrin in such concentration that death
      generally results within 4 days, usually exhibit a marked generalized analgesia,
      both superficial and deep. Gassed cats react with no obvious sign of pain to
      operative interferences, including laparotomy and gentle friction of the parietal
      peritoneum. The analgesia develops within a few hours after gassing, and reaches
      its maximum in about 24 hours. With dimethylsulfate the analgesia may persist for
      6 months; with chloropicrin practically normal sensitiveness has been observed 7
      days after gassing. This analgesia is considered to be caused and maintained
      largely by a general, low grade, tissue aspbyxia which is chiefly of pulmonic
      origin.

PMID- 19868606
TI  - THE TWORT-D'HERELLE PHENOMENON : II. LYSIS AND MICROBIC VARIATION.
AB  - 1. When the few individuals still alive in a dissolved culture of Bacillus coli
      are transplanted on slanted agar, a culture results which possesses new
      characteristics. First observed by Bordet and Ciuca, this culture received the
      temporary name of modified coli. In the study described above, we found that this
      modified coli is very heterogeneous and that its three principal characteristics,
      resistance to lysis, lysogenic properties, and mucoid growth, are shared among
      different types of organisms that can be isolated when the normal original coli
      (coli O) is plated together with increasing quantities of the lytic agent: (a) a
      certain number of bacilli are just resistant enough to survive and grow in the
      presence of a moderate quantity of lytic agent, but they are still more or less
      sensitive and produce diseased, irregular, and lysogenic colonies; (b) a few of
      the organisms are able to resist concentrated lytic agent; they are entirely
      resistant and give round, healthy, and non-lysogenic colonies (coli O R 2); and
      (c) among these resistant bacilli only a very few are mucoid (coli 0 R 1). All
      these types are not motile and not fluorescent. 2. The original coli, when
      allowed to age, can be dissociated, as we have shown in a preceding paper (1),
      into two types of organisms, the non-motile coli S and the very motile coli R.
      Submitted to lysis, coli S gives a very small number, coli R a much greater
      number of resistant organisms (coli S R and coli R R), but both types never yield
      any mucoid growth. 3. An old culture of the modified coli obtained by Bordefand
      Ciuca, when streaked on agar plate, gives two types of colonies: a mucoid and
      fluorescent type (coli M 1) and a non-mucoid and translucent type (coli M 2).
      Both types are motile. Coli M 2, once isolated, keeps its individuality even
      after several passages in artificial media, but if again submitted to the lytic
      agent, a great number of mucoid bacilli are found among the organisms which are
      still alive. Consequently, different types of Bacillus coli differ greatly in
      their ability to give a mucoid growth when submitted to the lytic agent. Some,
      like coli S and coli R, do not possess this property at all. Others, like coli O,
      possess it to a certain extent, and some, like coli M 2, have it to a very high
      degree. 4. The mucoid and motile Bacillus coli M 1, when streaked every day on
      agar plates, remains indefinitely mucoid and motile, but occasionally a mucoid
      colony shows an indentation made up of non-mucoid growth, which, transplanted,
      gives a pure culture of non-mucoid and non-motile organisms, coli M 1 a. This new
      type possesses all the characteristics of the original strain of Bacillus coli,
      and therefore must be considered as a reversion. 5. The mucoid and motile
      Bacillus coli M 1, kept growing in synthetic medium, remains perfectly stable; on
      the other hand, when it is transplanted in broth, Bacillus coli M 1 turns very
      quickly into a non-mucoid but still very motile organism, or Bacillus coli M 1 b.
      This last type, which produces translucent colonies on agar and grows granular in
      broth, never reverts to the mucoid form, even in the presence of lytic agent. 6.
      A single strain of Bacillus coli has thus been made to yield eleven different
      forms, all distinguished by striking characteristics, but still possessing the
      specific properties of Bacillus coli. Nine of these forms have been submitted to
      antisera prepared with three different types (Bacillus coli O, Bacillus coli S,
      and Bacillus coli R). While seven out of these nine strains were agglutinated by
      any of the three antisera, only the original Bacillus coli (Bacillus coli O) and
      the reversion to the original type (Bacillus coli M 1 a) were not agglutinable,
      even by their corresponding antiserum; i.e., the serum obtained from a rabbit
      immunized with Bacillus coli O, which, however, agglutinated the other types.

PMID- 19868607
TI  - THE CULTIVATION AND BIOLOGICAL CHARACTERISTICS OF SPIROCHAETA OBERMEIERI
      (RECURRENTIS).
AB  - A study of the growth requirements of Spirochoeta obermeieri resulted in the
      perfection of a method which enabled us (1) to cultivate the organisms
      consistently from the blood of infected mice and rats, (2) to maintain the
      viability of cultures for periods of at least 3 to 7 weeks, and (3) to carry them
      on in successive subcultures by transplanting at intervals of 2 to 4 weeks. This
      method is essentially the same as the Noguchi technique for the cultivation of
      the Leptospira group, but emphasizes control of the physicochemical factors that
      act to limit and prevent growth and prescribes the conditions necessary to
      counteract the injurious influences. The main facts may be briefly summarized as
      follows: (a) Ascitic fluid, horse or rabbit serum may be used as culture fluids.
      (b) These fluids become progressively more alkaline on exposure to air. (c)
      Uniformly successful results depend chiefly on the proper adjustment and
      stabilization of the reaction. (d) A balanced reaction can be secured by adding
      1.0 per cent peptone broth or egg albumin as buffer, and covering the culture
      with a layer of oil. (e) The reaction limits for growth and survival are between
      pH 6.8 and 8.2, with the optimum at pH 7.2 to 7.4. (f) Spirochoeta obermeieri is
      a strict aerobe, consequently in order to permit adequate aeration, the oil layer
      should not exceed 1.5 cm. in height.

PMID- 19868608
TI  - THE IMPORTANCE OF DEXTROSE IN THE MEDIUM OF TISSUE CULTURES.
AB  - It is not advisable to enter into a discussion of these findings at the present
      time, owing to the lack of experimental evidence as to the exact nature of the
      vacuoles. Regardless of the nature of these bodies or of what factors produce
      them, they are structures abnormal to the connective tissue cells. The lack of
      dextrose in the medium of tissue cultures leads to some condition distinctly
      detrimental to the cells, resulting in their vacuolation and death, even when the
      medium contains abundant protein material. The addition of small amounts (0.5 to
      1 per cent) of dextrose to the medium delays the formation of vacuoles and
      prolongs the life of the culture. The addition of large amounts (2 to 5 per cent)
      prevents vacuolation of the cells, but so much dextrose usually leads to a change
      in the hydrogen ion concentration of the culture resulting in an acid condition
      which arises coincidentally with the degeneration of the cells.

PMID- 19868609
TI  - CONSTRUCTION OF AN OXYGEN CHAMBER FOR THE TREATMENT OF PNEUMONIA.
AB  - 1. The construction of an oxygen chamber is given. This chamber can be quickly
      filled with oxygen to any concentration up to 65 per cent and maintained at the
      desired concentration for an indefinite time. 2. The construction of ventilating
      system, cooling device, carbon dioxide remover, automatic oxygen analyzer, and
      filling and maintenance devices is given. 3. The chamber is designed so that
      pneumonia patients with anoxemia may be placed in it and breathe an atmosphere
      containing 40 to 60 per cent of oxygen. 4. The chamber is easy of ingress and
      egress, is economical in cost of operation, and comfortably accomodates patient
      and attendants so that adequate nursing and medical attention can be given at all
      times.

PMID- 19868610
TI  - THE TREATMENT OF ANOXEMIA IN PNEUMONIA IN AN OXYGEN CHAMBER.
AB  - 1. The use of an oxygen chamber in the treatment of pneumonia patients makes it
      possible to administer this gas for long periods of time under exactly known
      conditions. The medical and nursing care of the patient is greatly facilitated.
      2. Prolonged inhalation of oxygen varying from 40 to 60 per cent appears to be
      without harm. 3. Oxygen administered to intensely anoxemic patients almost
      immediately clears up this anoxemia. Cyanosis disappears with the anoxemia. 4.
      The removal of patients from the high oxygen while they are still sick and while
      examination shows that there are still extensive edema and infiltration of the
      lung results in a return of the intense anoxemia. 5. It is sometimes impossible
      to clear up the anoxemia, even when as high as 60 per cent of oxygen is given,
      especially when there are considerable edema and infiltration of the lungs. 6.
      Five cases in which the prognosis was grave recovered. Three cases, one of
      tuberculosis, one with a Pneumococcus Type III infection, and a third with a
      pneumonia superimposed on a chronic pulmonary condition, died. 7. In all cases
      there appeared to be an improvement in the patient's condition. In one case,
      particularly, with an intense degree of anoxemia, the patient became moribund and
      pulseless. Following the administration of 60 per cent of oxygen there was a
      lowering of the heart rate from 160 to 120, the return of the pulse to the radial
      artery, the color became bright pink, and there was a remarkable change in the
      clinical condition. 8. The anoxemia of pneumonia is due, in large measure, to an
      impairment of the respiratory surface of the lungs. The greater the lung
      involvement the greater the anoxemia. Especially is this so when the pneumonic
      process extends throughout the lungs so that there are many patches of
      bronchopneumonia, with accompanying bronchitis and edema, as evidenced by the
      presence of rales throughout the lungs. 9. Rapid and shallow breathing of the
      degree observed in pneumonia is, as far as present evidence shows, of less
      importance in the production of anoxemia.

PMID- 19868611
TI  - AN ORGANISM RESEMBLING BACILLUS ACTINOIDES ISOLATED FROM PNEUMONIC LUNGS OF WHITE
      RATS.
AB  - An organism obtained from the pneumonic lungs of eleven white rats is described.
      It has been maintained in pure culture in a number of instances. In young
      cultures the organism appears as a long slender bacillus. In older cultures on
      coagulated serum media characteristic club-like capsular material is formed. On
      blood agar characteristic swellings appear at one or both ends of the rod. These
      become more refringent, and the body of the organism begins to shrink. Finally
      only rounded spore-like refringent bodies are found. The organism is Gram
      negative.

PMID- 19868612
TI  - A THREE MONTHS OLD STRAIN OF EPITHELIUM.
AB  - 1. A strain of pure epithelial cells was obtained from the part of the iris which
      adheres to the extirpated lens. 2. The optimum condition under which epithelial
      cells grow in vitro is on the free surface of the plasma clot under a film of
      embryonic tissue juice. 3. The epithelial cells did not dedifferentiate. Although
      the strain is 3 months old, they grow as a pavement membrane and have kept their
      epithelial characteristics.

PMID- 19868613
TI  - STUDIES ON X-RAY EFFECTS : IX. THE ACTION OF SERUM FROM X-RAYED ANIMALS ON
      LYMPHOID CELLS IN VITRO.
AB  - Lymphoid cells, prepared from the thymus and lymph glands of rats, when suspended
      in the serum of x-rayed rats and incubated for 2 hours, increase in number from
      15 to 30 per cent, and mitotic figures are found among these cells in fairly
      large numbers. A like suspension of cells in normal serum undergoes rapid
      disintegration and in only one instance among a large number of films examined
      was a mitotic figure found. The stimulative effect of the serum from x-rayed rats
      endures from 1 to 2 hours after the exposure but is not detectable in the serum
      taken 17 hours or later after the treatment. Serum x-rayed in vitro is devoid of
      stimulative action. The lymphoid cells of rabbits and guinea pigs are so fragile
      as to make impossible the obtaining of counts accurate enough for experimental
      purposes. The serum of one species caused such rapid disintegration of the cells
      of another that it was impossible to determine the specificity of the reaction.

PMID- 19868614
TI  - THE MEASUREMENT OF INTRAVENOUS TEMPERATURES.

PMID- 19868615
TI  - VENEREAL SPIROCHETOSIS IN AMERICAN RABBITS.
AB  - Of 50 rabbits, otherwise regarded as normal, three adult females and two adult
      males (10 per cent) have been found to have in their genitoperineal region
      certain papulosquamous, often ulcerating, lesions. A recently purchased group of
      twenty rabbits contained six females (30 per cent) with similar lesions. This
      condition runs a chronic course and is characterized by the presence of a spiral
      organism closely resembling Treponema pallidum. The rabbit spirochete has the
      same morphological features as Treponema pallidum; it is possibly a trifle
      thicker and longer than the average pallidum. Long specimens measuring 30 micro
      are frequently encountered, and they show a tendency to form loosely entangled
      knots. A stellate arrangement of several organisms in a mass is frequently
      observed. In the lesion of one rabbit there were two types of spirochete, one of
      the variety just described, the other a somewhat coarser organism, closely
      resembling Treponema calligyrum found in a human condyloma, but a trifle thinner
      and longer. This organism is perhaps merely a variant type of the rabbit
      spirochete. The histological reactions are similar to, but considerably less
      cellular, than those occurring in typical primary syphilitic lesions. There is a
      marked hyperkeratosis and interpapillary infiltration not observed in scrotal
      chancre. The disease is transmissible to normal rabbits, in which the usual
      papular lesions can be readily reproduced in the genitoperineal region. In the
      first passages the incubation period varied from 20 to 88 days; subsequently one
      of the strains produced a lesion in 20 days on the second, and in 5 days on the
      third passage. No typical orchitis or keratitis was produced in the rabbits of
      the present series, although in one of the original rabbits (No. 4) scaly,
      papular lesions have developed on the nose, lips, eyelid, and paws. Monkeys
      (Macacus rhesus) failed to show any lesions within a period of 4 months after
      inoculation. In one instance transmission was accomplished through the mating of
      an infected female with a normal male. The Wassermann reaction was uniformly
      negative in the five rabbits with spontaneous lesions and in eighteen rabbits
      experimentally infected. Salvarsan had the same therapeutic effect on the lesions
      produced by the rabbit spirochete as on the experimental pallidum lesion of the
      rabbit. The organism belongs to the genus Treponema, and may be designated
      Treponema cuniculi.

PMID- 19868616
TI  - HEMOLYTIC ACTION OF A STAPHYLOCOCCUS DUE TO A FAT-SPLITTING ENZYME.
AB  - A staphylococcus was isolated from milk which is hemolytic with horse blood only
      in the presence of fat. Similar results were obtained with two other strains of
      staphylococci. The hemolysis is the result of the action of a fatty acid (or
      soap) upon the red blood cells. The fatty acid is formed by the action of a
      lipase elaborated by the staphylococcus. The corpuscles of different animals show
      slight variations in the ease with which they are hemolyzed by the
      staphylococcus. Attention is called to the desirability of testing for lipases in
      the study of staphylococci or of hemolysis.

PMID- 19868617
TI  - EXPERIMENTAL RICKETS IN RATS : IV. THE EFFECT OF VARYING THE INORGANIC
      CONSTITUENTS OF A RICKETS-PRODUCING DIET.
AB  - 1. Rachitic bone lesions may be produced in rats by a diet containing an excess
      of calcium, but deficient in phosphates. 2. Similar lesions follow a diet
      deficient in calcium, but containing an excess of phosphates. The endochondral
      lesions, however, are less pronounced. 3. A diet deficient in both calcium and
      phosphate induces atypical rickets. 4. Inorganic salts other than calcium or
      phosphate seem to be without influence upon the development or prevention of
      rachitic lesions. 5. The minimal amount of phosphate (calculated as P) required
      for normal calcification in young growing rats (30 to 50 gm.) on the diets used
      in these experiments is approximately 160 mg. per 100 gm. of diet. At 135 mg.
      individual variations come into play; at 110 mg., or less, rickets invariably
      follows. 6. An excess of calcium is not necessary to the production of the
      rachitic lesions. A reduction of the calcium lactate of Diet 84 to 0.6 per cent
      (111 mg. of Ca per 100 gm. of diet) still results in the development of typical
      rickets. 7. Adult rats react to a deficiency of phosphate in the diet by the
      production of calcium-free osteoid in abnormal amount about the spongiosa and
      cortex. There is not produced any alteration of the epiphyseal cartilage, as in
      growing animals.

PMID- 19868618
TI  - EXPERIMENTAL RICKETS IN RATS : V. THE EFFECT OF VARYING THE ORGANIC CONSTITUENTS
      OF A RICKETS-PRODUCING DIET.
AB  - 1. Casein phosphorus does not completely prevent the development of rickets when
      substituted in Diet 84 in amount equivalent to a protective dose of basic
      potassium phosphate. 2. The protection given by lecithin is equivalent to its
      phosphorus content. 3. The protection given by yeast is at least proportional to
      its phosphorus content. An amount carrying sufficient vitamine B to promote
      growth, but insufficient to provide adequate phosphorus, does not prevent
      rickets. 4. Vitamine A, in the form of butter or butter fat to the amount of 10
      per cent of the diet, neither prevents nor cures rickets. 5. The substitution of
      10 per cent of egg albumin in Diet 84 improves the nutrition, but does not
      prevent rickets. 6. The addition of meat to Diet 84, thereby supplying an
      abundance of phosphorus, promotes normal growth and normal bone formation. A diet
      consisting solely of meat and flour is inadequate for proper growth, and leads to
      changes in the bones comparable with those observed on a diet low in calcium, but
      rich in phosphorus. 7. A diet has been found which contains the necessary food
      elements for approximately normal growth, and in which the only known deficiency
      is phosphorus. This leads regularly to the production of rickets.

PMID- 19868619
TI  - MODIFICATION OF AN IMPROVED ANAEROBE JAR.
AB  - In the filtrates of typhus-infected tissues of guinea pigs can be occasionally
      found a substance which produces in these animals thermic reactions, lesions
      characteristic of experimental typhus, and, still less frequently, inimunity to
      later injections of active virus. The general indications are that this substance
      is not a living organism.

PMID- 19868620
TI  - EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER : IV. IMMUNIZING AND TOXIC
      AGENTS FOUND OCCASIONALLY IN FILTRATES OF TYPHUS-INFECTED TISSUES.
AB  - In the filtrates of typhus-infected tissues of guinea pigs can be occasionally
      found a substance which produces in these animals thermic reactions, lesions
      characteristic of experimental typhus, and, still less frequently, immunity to
      later injections of active virus. The general indications are that this substance
      is not a living organism.

PMID- 19868621
TI  - STUDIES ON X-RAY EFFECTS : X. THE BIOLOGICAL ACTION OF SMALL DOSES OF LOW
      FREQUENCY X-RAYS.
AB  - A study has been made of the biological effect of a small dose of soft x-rays
      given off by a special water-cooled tube with a window of thin glass, operated at
      (1/2) inch spark-gap and 11 milliamperes. Mice exposed for 1 minute show 2 days
      later in the blood an increase in the number of lymphocytes and in the lymphoid
      organs an increased number of mitotic figures. There occurs also a marked
      dilatation of the vessels of the suprarenals, particularly between the cortex and
      medulla. The latter condition did not appear until after 24 hours and was still
      present 14 days after the treatment. No change was detected in other organs. Mice
      treated in this way showed a high degree of resistance to cancer transplants. The
      amount of resistance varied with the time of the inoculation after the treatment.
      The resistance was not increased before 3 days after and was at its highest point
      10 days after the treatment.

PMID- 19868622
TI  - STUDIES ON X-RAY EFFECTS : XI. THE FATE OF CANCER GRAFTS IMPLANTED IN
      SUBCUTANEOUS TISSUE PREVIOUSLY EXPOSED TO X-RAYS.
AB  - An erythema dose of x-rays given direct to the exposed subcutaneous tissue and
      muscle greatly diminishes the susceptibility of the exposed area to transplanted
      cancer. The same dose given over the intact skin does not affect the resisting
      power of the underlying subcutaneous tissue. Histological examination shows that
      a few days after the exposure of the subcutaneous tissue there is a lymphoid
      infiltration of this tissue, which infiltration sometimes includes the muscle
      layers as well.

PMID- 19868623
TI  - STUDIES ON LYMPHOID ACTIVITY : VI. IMMUNITY TO TRANSPLANTED CANCER INDUCED BY
      INJECTION OF OLIVE OIL.
AB  - The experiments reported in this paper show that it is possible to render mice
      resistant to transplanted cancer by injections of a suitable quantity of olive
      oil. In the course of the development of the resistance a definite period of
      latency is detectable following the oil injection, and the maximum degree of
      resistance appears at about the 10th day. This state of resistance, as has been
      determined by histological studies, is preceded by a proliferation of the cells
      of the lymphoid germ centers and, after the cancer inoculation, is associated
      with a lymphoid infiltration about the grafts, as well as by a second stimulation
      of the lymphoid germ centers and an increase in the number of the circulating
      lymphocytes.

PMID- 19868624
TI  - THE ERYTHROPOIETIC ACTION OF GERMANIUM DIOXIDE : II. THE SOURCE OF THE
      ERYTHROCYTHEMIA PRODUCED BY GERMANIUM DIOXIDE IN THE ALBINO RAT.
AB  - A histological comparison of the liver, spleen, bone marrow, circulating young
      erythrocytes, and differential count in mature male and female albino rats
      receiving germanium dioxide with their litter controls not receiving this
      compound was made. It was found that the livers of the test animals in most cases
      showed a condition of capillary dilatation and that more erythrocytes were in
      these capillaries than were in those of the controls. There was no evidence of
      any red cell formation by the liver. The spleens of the test rats gave the
      impression of being slightly more congested and of having a slightly more dense
      concentration of cells in the Malpighian corpuscles than those of the controls.
      There was no evidence of an increased red cell destruction nor was there any
      evidence of splenic erythropoiesis. In the bone marrow of the rats which had
      received the germanium dioxide injections there was evidence of a marked
      stimulation in formation of nucleated erythrocytes, in that many more of these
      cells were found here than in the marrow sections of the controls. The
      circulating blood of the test rats contained more young red cells as demonstrated
      by the increased number of erythrocytes taking the polychromatic stain than did
      the blood of the controls. No noteworthy differences in the values for the
      various types of white cells in the circulation determined by the differential
      count could be found between the two groups. Using, then, as an acceptable
      criterion of erythropoiesis an increase in the number of erythrocytes in the
      circulation which is accompanied by an increase in the number of young red cells,
      and an increased number of nucleated erythrocytes in the bone marrow, we consider
      ourselves justified in concluding that germanium dioxide is a potent
      erythropoietic agent and the source of the erythrocythemia produced by this
      compound is the increased production of red cell precursors by the bone marrow
      stimulated to increased activity by the compound used.

PMID- 19868625
TI  - THE EFFECT OF FLOOD DIURESIS ON HEMOGLOBINURIA.
AB  - Flood diuresis so far lowers the renal threshold for hemoglobin that the pigment
      appears in quantity in the urine as result of a hemoglobinemia insufficient under
      ordinary circumstances to lead to the elimination of even a trace of it. In
      pathological conditions that involve blood destruction hemoglobin probably passes
      into the tubules much more often than it reaches the urine, being prevented
      therefrom by the resorptive activity of the tubular epithelium.

PMID- 19868626
TI  - SIGNIFICANCE OF THE HEMOSIDEROSIS OF PERNICIOUS ANEMIA.
AB  - The selective deposition of hemosiderin in the liver parenchyma during pernicious
      anemia does not constitute evidence that there is a hemolytic cause for the
      disease located in the portal region. The repeated introduction of small amounts
      of free hemoglobin into the general circulation, by the subcutaneous route,
      leads, as we have shown, to an identical siderosis. Larger amounts of hemoglobin
      cause a renal pigmentation equalling or exceeding the hepatic, a fact that is in
      keeping with what is known of the physiology of hemoglobin excretion and of the
      findings in human beings afteroutspoken hemolysis.

PMID- 19868627
TI  - THE RENAL ELIMINATION OF BILIRUBIN.
AB  - The elimination of bile pigment during jaundice is, for practical purposes,
      unincreased by diuresis from water by mouth. Possibly, though, the flushing of
      the kidneys tends to lessen pigment accumulation within these organs and thus to
      diminish a serious potential source of trouble in long continued jaundice. Flood
      diuresis from intravenous injections of salt solution markedly increases the
      output of bile pigment. It is important to know the effect of variations in the
      urinary output on the elimination of bile salts, but methods for the purpose are
      not available at present. The passage of bile pigment into the kidney cells
      during jaundice is attested by the presence in the freshly voided urine of
      desquamated renal elements specifically stained, stippled, or granulated with
      bilirubin. Pigmentation of this sort is readily to be distinguished from the
      indiscriminate staining of cellular debris that occurs in icteric urines on
      standing. It has clinical significance, furnishing direct evidence on the degree
      of renal change.

PMID- 19868628
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      VII. SEROLOGICAL REACTIONS.
AB  - Cultivation of Bacterium pneumosintes in the collodion sac dialysate of a tissue
      medium produces an antigen suitable for serological tests. Injection of dialysate
      cultures of Bacterium pneumosintes into rabbits results in the production of
      antibodies demonstrable by agglutination, precipitation, complement fixation, and
      phagocytic reactions. Four strains of Bacterium pneumosintes, three from the
      first epidemic influenzal wave (1918-19) and one from the second (1920), show
      identical antigenic characters. The blood serum of rabbits experimentally
      injected with the glycerolated active material of rabbit passages contains
      specific agglutinins for Bacterium pneumosintes, whereas normal rabbit serum does
      not.

PMID- 19868629
TI  - MUTATION OF THE BACILLUS OF RABBIT SEPTICEMIA.
AB  - Type G microbes, discovered in pure cultures of the rabbit septicemia bacillus,
      have been demonstrated to arise from the parent D form by mutation. The D --> G
      mutation takes place in broth cultures of pure-line strains of Microbe D, when
      these are kept for several days without transplant at 37 degrees C., or at room
      temperature, or in the ice box. The mutation is greatly inhibited by filtrates
      from 6 and 24 hour cultures of Microbe D, and to some extent by filtrates from 48
      hour cultures. The process of transformation takes place to a very slight extent
      or not at all in undiluted rabbit serum, but Type G colonies subcultured to this
      medium do not revert to the parent D form. The D --> G change is strongly
      inhibited in cultures made in simple beef infusion, or in 5 per cent rabbit serum
      beef infusion. Peptone would seem to be the constituent of plain broth which
      favors the process. In high concentrations of peptone, the mutation is rapid and
      may reach a degree of 90 per cent of the total organisms in 5 to 6 days. A
      distinct maximum of the relative number of Type G colonies as compared to the
      parent Type D is observable in plain broth and in some concentrations of peptone,
      when these are kept at 37 degrees C. for some days without transplant. Subsequent
      tests show the concentration of Type G microbes to diminish. The change in acid
      agglutination optimum exhibited by the mutant G forms implies a distinct change
      in bacterial protoplasm and would seem to be one of the most fundamental
      mutations so far described.

PMID- 19868630
TI  - SPONTANEOUS DECREASE OF THE SURFACE TENSION OF SERUM. I.
AB  - 1. Over 3,000 measurements of surface tension of sera have been made with the
      ring method, and they have yielded a new phenomenon, the spontaneous and rapid
      decrease of the surface tension of a serum in function of the time. 2. Generally,
      after 10 minutes the surface tension reaches a value which is practically
      constant. At least, the decrease is very much slower. After stirring, a rise
      occurs and a similar phenomenon takes place; but stability is not obtained as
      rapidly, requiring about 25 minutes. By stirring again, the same thing happens
      repeatedly, the slope of the curve being less marked each time, the rise in
      surface tension being slightly below each previous value, and the phenomenon
      undergoing a sort of damping. 3. An equation was established which expresses the
      experimental facts with an accuracy of about 0.2 per cent. It applies to the
      whole phenomenon, before and after stirring. It has only one characteristic
      constant, See PDF for Equation This formula, by simply changing t to c
      (concentration), expresses satisfactorily in general the phenomenon of adsorption
      in the surface layer; that is, the decrease in surface tension in function of the
      concentration. 4. Prolonged heat, at 55 degrees C., and time seem to inhibit this
      phenomenon. 5. When precipitation occurs in a serum, the bottom of the liquid,
      which contains the precipitate, has the highest surface tension. When stirred,
      the surface tension rises a little every time. The upper part, clear, with lower
      surface tension, shows the reverse phenomenon; after every stirring, the surface
      tension becomes a little lower.

PMID- 19868631
TI  - A CUTANEOUS NEMATODE INFECTION IN MONKEYS.
AB  - A number of monkeys (Macacus rhesus) were found to be infected with a nematode
      which gave rise to several types of skin lesions, subcutaneous nodules, edema
      about the joints, and elongated serpiginous blisters of the palms and soles. In
      the subcutaneous nodules were found larval forms of the nematode and possibly
      adult male forms. The reaction about these worms consisted of proliferation of
      fixed cells, and invasion of eosinophils, with subsequent presence of giant
      cells, young blood vessels, and finally capsule formation; eventually the worms
      were killed, eliminated, and the nodule disappeared. In the skin of the palms and
      soles the adult female worm burrowed in the epidermis, producing an elongated
      serpiginous blood blister that eventually became purulent. In this blister the
      worm laid her eggs; and by the bursting of the blister the eggs were discharged
      into the outer world and placed in a position to infect new hosts. The reaction
      in the epidermis was evidently not severe enough to interfere seriously with the
      health of the host or with the continuation of the egg-bearing period of the
      female parasite. This condition of almost perfect parasitism is an ideal one for
      the continuation of the life of this species of nematode. In so far as we are
      able to determine this is the first description of a nematode that lays its eggs
      in the epidermis. The provisional name of the parasite is Trichosoma cutaneum,
      1922.

PMID- 19868632
TI  - VIRULENCE AND MUTATION OF THE BACILLUS OF RABBIT SEPTICEMIA.
AB  - Type D, bacillus of rabbit septicemia, exhibits marked fixity of the character of
      virulence. This is true for cultures that are regularly transplanted on serum
      agar or in broth. It is also to be observed when organisms of this variety are
      subjected to unfavorable conditions; e.g., remaining for 9(1/2) days without
      transplant in plain broth. Under such conditions no decrease in virulence was
      observed. G forms which arose in the same culture during this time exhibited
      characteristic lack of invasibility. Different individuals of a given culture of
      Type D do not vary to a noticeable extent in virulence. This was ascertained by
      test of virulence of cultures arising from six individuals fished from Type D
      cultures by Barber pipette. A Type D culture subjected to passage in plain broth
      undergoes D --> G mutation. Type D and G individuals can be demonstrated to be
      present in the same culture. The virulence of such a mixed culture is
      proportional to the relative member of Microbes D and G present. This throws
      light on certain mechanisms of attenuation. The virulence of Type G can be raised
      to a considerable titer by animal passage. Such organisms do not, however, lose
      their characteristic of granular growth. This last, on the other hand, appears to
      intensify by animal passage. The acid agglutination zone of Type G strains which
      have been passed through animals shows a marked broadening. Microbe D owes its
      superior invasive power at least in part to its antiphagocytic activity, a
      property apparently not possessed by Microbe G.

PMID- 19868633
TI  - COLLODION SACS FOR AEROBIC AND ANAEROBIC BACTERIAL CULTIVATION.
AB  - A simple and convenient method is described for the preparation and use of
      collodion sacs for aerobic and anaerobic bacterial cultivation in vitro. The sacs
      are suitable for the study of various problems in bacterial growth and
      metabolism. By their use with the Smith-Noguchi tissue medium, certain
      microorganisms may be grown in the absence of the confusing, antigenic protein
      precipitate characteristic of cultures containing fresh tissue, and thus the
      organisms are obtained in a suitable condition for serological study.

PMID- 19868634
TI  - HEAT AND GROWTH-INHIBITING ACTION OF SERUM.
AB  - The inhibiting action of homologous serum on the proliferation of fibroblasts in
      vitro was increased after the serum had been heated at 56 degrees and 70 degrees
      C. This action decreased after the serum had been heated at 100 degrees C.

PMID- 19868635
TI  - CICATRIZATION OF WOUNDS : XIII. THE TEMPERATURE COEFFICIENT.
AB  - For a rise of temperature of 10 degrees C., the rate of cicatrization was
      increased about twofold. This result could be expected, since wound healing is
      closely related to the phenomenon of growth and regeneration. It is classical
      that changes in temperature affect the metabolism and the development of certain
      organisms in the same manner as a chemical reaction. In spite of the complexity
      of the factors which bring about the cicatrization of a wound, it appears that
      the velocity of the phenomenon depends on the rate at which certain chemical
      changes take place.

PMID- 19868636
TI  - ACTION OF ANTIGEN ON FIBROBLASTS IN VITRO.
AB  - IT MAY BE CONCLUDED THAT, UNDER THE CONDITIONS OF THE EXPERIMENTS: 1. A small
      amount of foreign protein added to the culture medium does not modify the rate of
      proliferation of fibroblasts. 2. A large amount of foreign protein added to the
      culture medium decreases markedly the rate of proliferation of fibroblasts
      cultivated previously in homogenic medium, while it does not decrease the rate of
      proliferation of fibroblasts cultivated previously in the presence of a small
      amount of the foreign protein. 3. Fibroblasts in vitro respond to the presence of
      an antigen in the culture medium by becoming immunized against its action.

PMID- 19868637
TI  - THE VASELINE TUBE AND SYRINGE METHOD OF MICRO GAS ANALYSIS OF BACTERIAL CULTURES.
AB  - There has been described the use of the vaseline tube and the tuberculin syringe
      for the study of gas production by bacteria. A comparison is made of some of the
      results obtained by the use of the method here described, the Smith fermentation
      tube, and the tube of Eldredge and Rogers. The reports of CO(2) production by
      certain streptococci by Ayers, Rupp, and Mudge and by Bacterium typhosus by
      Nichols have been confirmed by the author's method. The data presented serve to
      illustrate the accuracy and technical possibilities of the method. In addition to
      economy of glassware, medium, and labor, the vaseline tube and syringe method of
      micro gas analysis possesses the following advantages. (1) Gas produced above
      either liquid or solid media may be measured and analyzed. (2) The gas produced
      may be measured in terms of a definite and constant quantity of medium used. (3)
      The vaseline tube provides a closed system from which gases do not escape into
      the air. (4) Separate determinations of the CO(2) produced in and above fluid
      media may be made. (5) Determinations may be made from very small samples of
      material. (6) Numerous gas analyses of the same culture may be made at various
      times during the growth of the culture without contaminating or destroying it.
      (7) Gas production may be observed under both anaerobic and controlled aerobic
      conditions.

PMID- 19868638
TI  - STUDIES ON THE PNEUMOCOCCUS : I. ACID DEATH-POINT OF THE PNEUMOCOCCUS.

PMID- 19868639
TI  - STUDIES ON THE PNEUMOCOCCUS : II. DISSOLUTION OF PNEUMOCOCCI AT VARYING HYDROGEN
      ION CONCENTRATIONS. EFFECT OF TEMPERATURE, PREVIOUS KILLING OF THE ORGANISMS, AND
      FRESH HUMAN SERUM ON THE PHENOMENON. BEHAVIOR OF OTHER ORGANISMS.
AB  - Suspensions of living pneumococci in approximately isotonic standard solutions
      and in approximately isotonic bouillon with pH varying from about 4.0 to 8.0
      after incubation show dissolution of organisms in those solutions having a pH
      higher than about 5.0. Dissolution is most marked at a critical range of about pH
      5.0 to 7.0. Some dissolution also takes place toward the more alkaline end of the
      scale. No dissolution occurs at the most acid end of the scale. Dissolution in
      the standard solutions occurs at incubator, room, and ice box temperature. It is
      less marked at ice box temperature. Dissolution takes place in standard pH
      solutions with pneumococci allowed to grow and die out in glucose bouillon but
      unlike dissolution with living organisms is progressive from the acid toward the
      alkaline end of the scale. Pneumococci killed by heat for I hour undergo less
      dissolution than living organisms, the general character of the curve being
      similar to that with living organisms. Pneumococci killed by heat at 100 degrees
      C. for 5 minutes do not undergo dissolution. The addition of fresh human serum to
      the suspensions of pneumococci at varying pH prevents dissolution. Dissolution of
      pneumococci takes place more rapidly at pH 6.1 in standard solutions in which
      large numbers of pneumococci have been previously dissolved than in fresh
      standard solutions at the same pH. The dissolution of pneumococci under the
      conditions of the experiments may be ascribed to an enzyme derived from the
      bacteria themselves. Other organisms such as Streptococcus viridans and
      hoemolyticus and Staphylococcus aureus do not undergo dissolution under
      conditions similar to those to which the pneumococcus was exposed.

PMID- 19868640
TI  - STUDIES ON THE PNEUMOCOCCUS : III. DISSOLUTION OF PNEUMOCOCCI IN PNEUMONIC
      CELLULAR MATERIAL AT VARYING HYDROGEN ION CONCENTRATIONS. RESISTANCE OF CERTAIN
      OTHER ORGANISMS TO DISSOLUTION.
AB  - Pneumococci of Types I, II, and III undergo dissolution when mixed with cellular
      material from the pneumonic lung at a pH of 6.95 and 5.5, but not at a pH of 4.5.
      An enzyme derived from the bacteria themselves or from the cellular material may
      be the cause of the dissolution. Streptococcus hoemolyticus and Streptococcus
      viridans do not undergo dissolution under similar experimental conditions.

PMID- 19868641
TI  - STUDIES ON THE PNEUMOCOCCUS : IV. EFFECT OF BILE AT VARYING HYDROGEN ION
      CONCENTRATIONS ON DISSOLUTION OF PNEUMOCOCCI.
AB  - Dissolution of pneumococci takes place most rapidly in bile at a slightly
      alkaline reaction. This is probably due to death of the organisms and activation
      of the endocellular enzyme at its optimum hydrogen ion concentration.

PMID- 19868642
TI  - SURFACE TENSION OF SERUM : II. ACTION OF TIME ON THE SURFACE TENSION OF SERUM
      SOLUTIONS.
AB  - The application of the ring method to the measurement of solutions of serum and
      of certain organic compounds has brought forth new facts, mainly the decrease of
      the surface tension of such solutions in function of time. 1. In serum diluted at
      such a low concentration as 1:1,000,000 in NaCl, physiological solution, the
      surface tension of the liquid is lowered by 3 or 4 dynes in 2 hours; at
      1:100,000, by about 11 dynes (mean value) in 2 hours, and by 20 dynes in 24
      hours; at 1:10,000 by about 13 to 16 dynes in 2 hours. 2. The drop in surface
      tension is much more rapid in the first 30 minutes and follows generally the law
      of adsorption in the surface layer in function of the time. 3. Stirring or
      shaking after the drop causes the surface tension to rise, but generally below
      its initial value. 4. The same phenomena occur when using sodium oleate,
      glycocholate, or saponin instead of serum. 5. For every serum, as well as for the
      substances mentioned above a maximum drop occurs in certain conditions at a given
      optimum concentration. 6. Not only are the substances which lower the surface
      tension adsorbed in the surface layer, in the case in which they are present with
      crystalloids, but also the crystalloids themselves, in contradiction to Gibbs'
      statement. This is plainly shown by the evaporation of such solutions in watch
      glasses which, instead of a small group of sharp, large, well defined crystals at
      the bottom, leaves a white disc almost as large as the initial free surface
      itself, due to the liberation of the salt by the surface layer as it crawls down
      the concave surface of the glass. 7. In these conditions, solutions of serum are
      characterized by a very peculiar periodic and concentric distribution of the
      crystals, at a concentration of 1:100 only. The same ring-like aspect is observed
      with sodium oleate, glycocholate, and saponin, but not at the same concentration,
      as was to be expected, since serum is a solution in itself.

PMID- 19868643
TI  - PATHOLOGY OF THE DERMATITIS CAUSED BY MEGALOPYGE OPERCULARIS, A TEXAN
      CATERPILLAR.
AB  - 1. The dermatitis caused by contact with the larva of Megalopyge opercularis is
      produced by a poison introduced by the hollow, specialized setae of its cuticular
      tubercles. It is not produced by the ornamental hairs, or by the tissue juices of
      the animal. 2. The poison appears to be of the nature of a venom, combined with
      protein vehicles, and may be itself a protein. 3. It is rendered inert by
      boiling, or by heating to 55 degrees C. for a considerable period of time. 4. It
      is apparently stored in sacs at the base of the setae, but whether secreted
      there, or by hypodermal glands, remains to be determined. 5. It diminishes in
      virulence after the larva has spun its cocoon, and is no longer active after the
      caterpillar is dead. 6. The poisonous spines cause localized necrosis of the
      human epidermis, followed by the formation of small vesicles. The cellular
      reaction to the poison is chiefly lymphocytic.

PMID- 19868645
TI  - STUDY OF THE ACTION OF FOUR AROMATIC CINCHONA DERIVATIVES ON PNEUMOCOCCUS. A
      COMPARISON WITH OPTOCHIN.
AB  - It has been shown with one strain of pneumococcus (Type 1, Neufeld), that
      hydroquinine chloroacetanilide (C 29), hydroquinine p-chloroacetylaminophenol
      hydrochloride (C 36), hydroquinine m-chloroacetylaminophenol hydrochloride (C
      40), and hyroquinine 4-chloroacetylaminopyrocathecol hydrochloride (C 110) have a
      rapid pneumococcidal activity both in vitro and in the peritoneal cavity of mice,
      and to a lesser extent in rabbits. In comparison, optochin is slower in action,
      but its power is not so easily destroyed either in vitro or in vivo. The
      introduction of the hydroxy group of the benzene nucleus of hydroquinine
      chloroacetanilide changes the relationship between organotropism and
      bacteriotropism. In comparing the rapidity of in vitro bactericidal action and
      intraperitoneal toxicity, C 29 exhibits the most rapid pneumococcidal action and
      is the most toxic for mice. C 36, the para-hydroxy derivative, is one-fifth as
      toxic as C 29 and only one-tenth less active bactericidally. C 40 is one-half as
      toxic and has approximately the same bactericidal power, while C 110 is one-eigth
      as toxic and one-fifth as pneumococcidal; and optochin is one-sixth as toxic and
      has one-fifth the bactericidal action. Arranged in the order of their ability to
      kill pneumococci when injected simultaneously with them into the peritoneal
      cavity, the drugs are: C 40, C 110, C 36, optochin, and C 29. The
      chemotherapeutic action of the aromatic compounds is essentially local in
      character. But by per os therapy there is demonstrated a certain amount of
      diffusion of this activity, not shown by any other method of administration, C 40
      and C 110 having about the same value as optochin. Intravenous injection of the
      drugs in small doses destroyed to a greater or less extent the natural defenses
      of the animal, optochin being perhaps less injurious than the aromatic compounds.
      This same destruction of natural resistance followed intraperitoneal and
      subcutaneous injections of the chemicals as measured by intravenous injections of
      the organisms. The maximum tolerant dose in a single injection (intraperitoneal)
      is not so efficacious as the same dose divided in fifths and injected at hour
      intervals. Optochin under these conditions is not so active as the aromatic
      compounds. In general, repeated doses are more curative than single. There is a
      zone between the therapeutic and toxic doses, both single and repeated, for all
      these chemicals alike, where the natural resistance of the animal to an infection
      is reduced. This effect is noted especially with C 29, C 36, and C 40. In the
      case of optochin the therapeutic dose is nearer the toxic than with C 110, C 36,
      and C 40. Apparently these chemicals exhibit a variability in in vivo
      bactericidal activity according to different strains of pneumococci and numerical
      virulence.

PMID- 19868644
TI  - A TEN YEAR OLD STRAIN OF FIBROBLASTS.

PMID- 19868646
TI  - A FURTHER INQUIRY INTO THE SOURCE OF THE VIRUS IN BLACKHEAD OF TURKEYS, TOGETHER
      WITH OBSERVATIONS ON THE ADMINISTRATION OF IPECAC AND OF SULFUR.
AB  - That the ovum of Heterakis papillosa is an important source of the virus in the
      natural transmission of blackhead in turkeys is suggested by experimental
      evidence obtained in the present investigation. Confirmatory morphological
      evidence has not thus far been obtained to establish definitely that this worm
      serves as the invertebrate host of Histomonas meleagridis. It is possible
      occasionally to produce blackhead in turkeys by feeding large amounts of the
      virus alone, as obtained in liver lesions. This artificial procedure is, however,
      not duplicated in nature since the lesions of the disease are not eaten by young
      turkeys. The intentional contamination of the food of young turkeys with dirt
      taken from hen yards has in the present experiments invariably produced
      blackhead. The conditions provided are essentially those that prevail in many
      farmyards. The identity of blackhead infection in common fowls with that of
      turkeys is indicated by the production of the typical disease in a turkey by the
      inoculation of liver lesions obtained from a diseased chicken. It is not known
      whether variation in the period between the ingestion of Heterakis ova and the
      onset of the disease is dependent on the absence of the virus for a time or on
      the absence of the conditions necessary for invasion. Under experimental
      conditions a large proportion of the Heterakis ova fail, at least when fed by
      hand, to hatch out in the intestine, but, passing through, may later be taken up
      with contaminated food. This is shown by the occurrence in the ceca of larvae in
      various stages of development long after the Heterakis material is fed. Ipecac,
      like other drugs previously tested, is found to be of no practical value in the
      control of blackhead. It has no deleterious effect on Histomonas in the tissues
      and does not prevent the development of Heterakis. Its daily administration to
      the limit of tolerance fails to prevent infection or a fatal outcome in the
      naturally acquired disease. The fact that ipecac may delay the onset of the
      infection may perhaps be due to some physiological property of this drug. Sulfur
      administered daily in large amount likewise, possibly on account of its evacuant
      action, tends to delay infection. Recovery from inoculated blackhead is
      associated with a degree of immunity. That this is not permanent is indicated by
      the appearance of symptoms of blackhead several months after recovery from the
      inoculated disease. The fact that blackhead sometimes appears in mature turkeys
      that have been kept constantly on infested ground suggests that these birds may
      suffer from repeated attacks. Observations made during the course of the present
      investigations confirm previous conclusions as to the flagellate character of
      Histomonas meleagridis.

PMID- 19868647
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      VII. FURTHER OBSERVATIONS ON THE CULTURAL AND MORPHOLOGICAL CHARACTERS OF
      BACTERIUM PNEUMOSINTES.
AB  - After artificial cultivation for a period of over 3 years Bacterium pneumosintes
      has maintained its original morphological and cultural characteristics, when
      grown in the original medium. Adaptation to a saprophytic existence has been
      accompanied by a loss of pathogenicity. Our strains now grow readily under
      strictly anaerobic conditions in a variety of media with peptone broth as a base,
      enriched with fresh tissue, blood, or by the growth of other bacteria. Surface
      colonies have been obtained on blood agar plates in. an anaerobic jar. These
      various methods of cultivation are adapted to special purposes. In broth cultures
      Bacterium pneumosintes grows in larger forms than in the ascitic fluid-tissue
      medium, but the identity of the microorganisms is proved by their serological
      reactions and by reversion to the minute forms on transfer to the original
      medium.

PMID- 19868648
TI  - THE PEPTASE, LIPASE, AND INVERTASE OF HEMOLYTIC STREPTOCOCCUS.
AB  - 1. A method has been outlined by which the enzymes of hemolytic streptococcus may
      be extracted with comparative ease. 2. The peptolytic enzyme is active between pH
      4.4 and 8.7 with an optimum action at pH 7.2. It is destroyed in neutral
      phosphate solution at a temperature of 57 degrees C. continued for 10 minutes and
      at pH 5.0 deteriorates slowly at 37 degrees C. Concentration experiments with
      solutions of the enzyme have shown that it resembles other enzymes. It is
      exceedingly susceptible to chloroform and its action is inhibited by dilutions of
      gentian violet. Casein is attacked but serum albumin is not digested after 3 days
      at 37 degrees C. 3. The invertase is active between approximately pH 5.0 and 8.0
      with an optimum of pH 7.0. It is destroyed by a temperature of 52 degrees C.
      continued 10 minutes at an acid concentration of pH 7.0, or after 6 hours at 37
      degrees C. at pH 5.0. At this acidity it is more susceptible to heat than the
      peptase. 4. The lipase is active above pH 5.6. The greatest activity was observed
      at pH 7.9. It is completely destroyed after heating to temperatures over 55
      degrees C. for 10 minutes and resembles the invertase in its susceptibility to
      acid.

PMID- 19868650
TI  - MEGACARYOCYTES IN THE PERIPHERAL CIRCULATION.
AB  - A megacaryocyte is seen commonly as an occasional cell in the peripheral blood of
      patients with myelogenous leucemia. Less commonly they appear in relatively large
      numbers. These giant cells also may occur in the blood under other conditions.
      Their presence is indicative of a bone marrow under intense strain.

PMID- 19868649
TI  - STUDIES ON EXPERIMENTAL PLETHORA IN DOGS AND RABBITS.
AB  - 1. The effects of repeated transfusions of blood on the blood-destroying and
      blood-forming apparatus of normal and splenectomized dogs and rabbits have been
      described. An anemia which developed despite continued blood transfusions in two
      dogs splenectomized during plethora has also been studied. 2. The decrease or
      absence of reticulocytes from the blood stream during plethora and their increase
      during "plethoric anemia" are evidently due to depression and activation of bone
      marrow activity. The response of the bone marrow is not immediate upon the onset
      of anemia, but is delayed for several days. 3. The blood volume studies have
      served to emphasize the constancy of plasma volume under extreme experimental
      conditions, and the adaptability of the circulatory system to large increases in
      total blood volume. 4. Blood destruction and elimination, as measured by urobilin
      excretion, are greatly increased during the stage of plethora, but still more so
      during "plethoric anemia." 5. Despite intravenous introductions of large
      quantities of nitrogen in the form of whole blood, the total nitrogen, urea, and
      ammonia in the urine and feces are not raised appreciably for some time after the
      onset of plethora. The normal organism is apparently able to store large
      quantities of blood or its decomposition products. Upon the onset of a "plethoric
      anemia," there is an increase in urinary total nitrogen and urea excretion, which
      was lowered during the course of the anemia. Albuminuria is also found at this
      time. Other nitrogenous constituents and phosphates show no striking changes. 6.
      Blood pigment, chiefly in the form of hemosiderin, is deposited in enormous
      quantities in the spleen, liver, lymph nodes, and bone marrow. It occurs chiefly
      in phagocytes, though in late stages large extracellular masses are found.
      Increased pigment deposition can still be found several months after transfusions
      have been stopped. 7. Phagocytes containing erythrocytes are found rarely, if at
      all, and only in the acute cases, but their occurrence may be greatly masked by
      the coexistent congestion. 8. In splenectomized dogs the tendency to "plethoric
      anemia" is much more apparent, although a direct connection between the two
      events is not established. In rabbits, whose spleens constitute only 0.05 per
      cent of body weight, "plethoric anemia" is more easily produced. 9. In
      splenectomized animals pigment-bearing phagocytes are especially prominent in the
      liver, although lymph nodes and bone marrow apparently share in the extra work
      caused by the absence of the spleen. Lymph nodes with some of the characteristics
      of hemolymph nodes were found in various localities in all animals that had been
      made plethoric. 10. In rabbits blood pigment is deposited in the hemopoietic
      organs in large amounts, but under the conditions of our experiments, the picture
      and the experiment have been constantly complicated by early fatal intravascular
      agglutination and thrombosis. In the rabbit, as in human hemochromatosis, the
      pigment is found in two forms: hemosiderin granules, and smaller, dark spicules
      that do not react to the usual iron stains (probably hernofuscin). The latter
      pigment is also found seeded through the cells of the liver parenchyma.

PMID- 19868651
TI  - IMMUNOLOGICAL DISTINCTIONS OF TWO STRAINS OF THE MOUSE TYPHOID GROUP ISOLATED
      DURING TWO SPONTANEOUS OUTBREAKS AMONG THE SAME STOCK.
AB  - Two strains of the paratyphoid B-enteritidis group causing separate epidemics of
      mouse typhoid among 2,500 to 4,000 cancer breeding mice are found to be
      antigenically different. Mouse Typhoid I, isolated from the first outbreak, is
      related but not identical with two strains of enteritidis, while Mouse Typhoid II
      is related to but not identical with the human paratyphoid B strains. In a
      separate paper in this series, Webster has identified Mouse Typhoid II strain
      with Bacillus pestis caviae Smith and has suggested its close relation to the
      Bacillus aertrycke (mutton) group of Schutze.

PMID- 19868652
TI  - SURFACE TENSION OF SERUM : III. RECOVERY AFTER LOWERING BY SURFACE-ACTIVE
      SUBSTANCES.
AB  - 1. The equilibrium of the serum corresponding to its normal minimal surface
      tension is as stable and difficult to break, under ordinary conditions, as the
      osmotic tension equilibrium. The addition of a strong surface-active substance
      (sodium oleate, glycocholate, or taurocholate), will not lower it definitely,
      unless the substance is present in large amounts and in solution. After the first
      rapid drop has occurred, a process of recovery takes place, which brings back the
      normal surface tension in a short time (from 2 to 6 minutes in the case of pure
      serum). As a drop in the surface tension of the serum of animals may be very
      injurious to the red cells, this process of recovery is a normal one of defense
      in all cases in which surface-active substances (bile) are set free in the blood.
      2. When diluted, the serum shows the same phenomenon to a smaller extent; the
      time of recovery is very much longer and the final surface tension is always
      lower than the original value. At a dilution of 1/10,000, no recovery takes
      place, the dilution being too high to overcome the lowering action of 1/10,000 of
      sodium oleate. 3. The recovery is stronger when the surface-active substance is
      added powdered or in a highly concentrated solution, and not stirred. 4. The
      recovery does not seem to be inversely proportional to the concentration of
      sodium oleate, when added superficially. Doubling the concentration at 1/2,000,
      for example, gives the same curve of recovery. This happens under certain
      conditions; namely, when the liquid is not stirred after the addition of sodium
      oleate. 5. This recovery is due to a purely physical phenomenon, namely
      adsorption, and is not specific for the serum. Other colloidal solutions, such as
      gum arabic, egg albumin, gelatin, and silver and gold sols, show it, only to a
      smaller degree. The process of recovery follows a logarithmic law in all cases,
      expressed by an equation of the form See PDF for Equation 6. Temperature affects
      this phenomenon. At first it enhances it, but finally decreases it. This would
      seem to connect the loss of the property of the serum known as complement in a
      serum with a modification of the physical properties of this serum. This
      phenomenon is being investigated further.

PMID- 19868653
TI  - INFECTIOUS MOTOR PARALYSIS IN YOUNG RABBITS.
AB  - 1. The attempt to infect young rabbits and guinea pigs with material containing
      in all probability the virus of human infantile paralysis failed. 2. Failure to
      infect the primary animals almost of necessity brought failure with the secondary
      flea-bitten animals. It is, however barely conceivable that a non-infectious form
      of an organism might circulate in the blood of the primary animal and that this
      form, through development in an intermediate host, the flea, might become
      virulent for the secondary flea-bitten animal. 3. Incidentally, and presumably
      accidentally, a paralytic disease was observed in young rabbits associated with
      the presence of an organism showing certain definite characters. So far as we
      know this paralysis and the associated organism have not been previously
      described. 4. This organism is found widely distributed in the organs of the
      affected animals and can be demonstrated in the urine. The active destruction by
      the organism of the nerve cells of the spinal cord is particularly striking, and
      gives complete explanation for the paralysis observed clinically. 5. With the
      organism present in the urine the spread of the disease by contact can be easily
      understood. 6. The transfer of the infection from animal to animal by fleabites
      is possible but not probable. 7. The nature of the observed organisms is in
      doubt. They represent probably an intermediate stage in the life history of some
      protozoan parasite.

PMID- 19868654
TI  - THE STRUCTURE AND DIFFERENTIATION OF THE SPECIFIC CELLULAR ELEMENTS OF THE PARS
      INTERMEDIA OF THE HYPOPHYSIS OF THE DOMESTIC PIG.
AB  - The bearing of these results on the Herring-Cushing theory of pituitary secretion
      is apparent. For the first time a true secretion antecedent has been demonstrated
      in the cells of the pars intermedia, an antecedent which appears in the cells at
      the same period of development at which active pressor effects may be obtained
      from the gland extracts. The route of export of this material from the gland to
      its point of utilization, however, is unknown; it may go by way of the blood or,
      as required by the Herring theory, by the transneural route to the third
      ventricle. The objections to the latter conclusion have been amply expanded in
      the introduction to this paper, but here may be emphasized the fact that the
      fetal pig hypophysis contains no hyaline bodies. Indeed they are rare in the
      adult, though there may be seen in the cells of the pars nervosa in the processes
      of its intrinsic cells, granular deposits which we believe to be the antecedents
      of the hyaline bodies but which in the pig rarely are discharged and aggregated
      into discrete masses as in other mammals. The fact that some observers have
      obtained positive pressor effects from the nervous part of the posterior lobe,
      exclusive of the pars intermedia, need not weigh very heavily in attempting to
      trace the course of the secretion, when we reflect that the difficulties of
      making such a mechanical separation are almost insuperable, and that the chemical
      product of the pars intermedia is so soluble and vanishes from the cells so
      rapidly that it may well be diffusible through the thin membranes which intervene
      and penetrate post mortem into adjacent parts. We are inclined, therefore, to the
      view that the secretion leaves the gland by the vascular route rather than by way
      of the interfibrillar spaces of the pars nervosa.

PMID- 19868655
TI  - AN OUTBREAK OF MOUSE TYPHOID AND ITS ATTEMPTED CONTROL BY VACCINATION.

PMID- 19868656
TI  - EXPERIMENTAL EPIDEMIOLOGY : I. AN ARTIFICIALLY INDUCED EPIDEMIC OF MOUSE TYPHOID.
AB  - In this paper we have described the first part of an experimental study of the
      epidemiology of mouse typhoid. One set of data has been presented on the basis of
      which little or no analysis has been attempted. The immediate object has been
      rather to collect materials than to undertake to account for the phenomena
      encountered. It is obvious that the factors involved in the inquiry are
      intricate, but it is believed that they are not necessarily or all beyond
      disentanglement. About 500 mice in all have been studied in an experimental
      village, brought together in increments among a population in which mouse typhoid
      experimentally induced was prevailing. The results have been presented according
      to two phenomena; namely, mortality or death rate, and bacillus carriage rate.
      The material does not lend itself to consideration according to morbidity rates.
      If it were established that every instance of attack, when not fatal, was
      attended by carrier production for the bacillus of mouse typhoid, reliable
      morbidity tables could be constructed. In the absence of this certain criterion,
      the materials here presented can be dealt with only as mortality data. This fact
      is attended with obvious disadvantages in respect to the epidemiological material
      assembled regarding infectious disease in man. In spite, however, of the
      drawbacks, it is already evident that the results obtained by the sort of inquiry
      here described may come to throw no inconsiderable light on moot problems on the
      origin, mode of spread, and manner of decline of epidemic diseases in general.
      The analysis of the strains by selecting single cells and thus establishing
      substrains has yielded results which may eventually have value in explaining
      fluctuations in virulence. Among the positive data arising from the experiments
      with such cultures are, first, that there have been obtained by mechanical means
      from the ordinary bacteriologically pure culture, single cell strains exhibiting
      slightly different pathogenic activity, whether administered by mouth or
      parenterally, and second, that more regular results are obtained with
      intraperitoneal injections of these strains than with the parent strain. Among
      the negative results to be recorded are the failures of two single cell strains
      to incite an epidemic among mice under conditions known to be suitable when the
      parent strain is used.

PMID- 19868657
TI  - EXPERIMENTAL EPIDEMIOLOGY : II. EFFECT OF THE ADDITION OF HEALTHY MICE TO A
      POPULATION SUFFERING FROM MOUSE TYPHOID.
AB  - 1. A kind of mouse village was set up into which was introduced a small number of
      mice fed on a culture of so called mouse typhoid (Bacillus pestis cavice of the
      Bacillus paratyphosus B group) bacillus. The spread of the infection so induced
      to the cages, or "homes," of the other mice was left to accident through the
      attendant who fed the animals and cleaned the cages. That this means was likely
      to be sufficient was deduced from the epidemic reported by Lynch. A spot map was
      kept throughout the experiments which extended from 1919 into 1922. 2. The first
      effect of the exposure of normal mice to a much smaller number of mice fed on the
      culture is to set up a sporadic, not an epidemic outbreak of mouse typhoid. This
      is the regularly recurring incident of the experiment as shown by low mortality
      and low cage attack rate. Such a sporadic prevalence is self-limited in time. 3.
      The introduction of fresh, normal mice into a community in which sporadic deaths
      are occurring leads regularly, not to the further extension of the sporadic
      deaths, but to an epidemic spread, as shown by high mortality and high cage
      attack rate. The epidemic begins with deaths among the new mice, but extends to
      the old mice which succumb later. The spread ceases and the wave subsides before
      all the mice have succumbed. A state of equilibrium between the infecting
      bacillus and the surviving mice is reached; no more deaths occur. The epidemic
      outbreak, therefore, is also self-limited in time. 4. If, now, another new
      addition of normal mice is brought into the potentially infected community, the
      events are reenacted; deaths occur among the new, another epidemic wave sweeps
      through the population, again claiming victims among the previous survivors.
      Through the replacement of the destroyed mice with fresh, normal mice, epidemic
      wave after wave is produced, until certain groups of old survivors are entirely
      wiped out. There seems to be no limit to this process, as there will always be
      survivors at least of the later groups added. 5. The dying down of the epidemics
      and the attaining of the equilibrium do not mean the elimination of all the
      bacilli. Potential infection still lurks in mouse "carriers" and on the hands of
      the attendant. No successful method of completely removing the bacilli from the
      hands of the attendant was found. 6. The maintaining of the epidemic waves is
      dependent on the presence of new lots of mice, whether supplied from without or
      produced within through new births. It is the latter sources which provide the
      consumable material in such natural epidemics as that described by Lynch. Hence
      their slower movements as compared with the epidemic spreads and rise and fall of
      the epidemic waves in the artificially propagated instances in which new batches
      of mice are brought into the village in bimonthly intervals. 7. The evidence at
      hand is to the effect that the degree of infectivity of "mouse typhoid" bacilli
      is highly fluctuating, and it appears that all the bacilli which are included
      under that name, classed variously as Bacillus enteritidis, Gartner's bacillus,
      Bacillus paratyphosus B, Bacillus suipestifer, and Bacillus pestis cavioe, infect
      mice in a similar, possibly indistinguishable manner, inducing self-limited
      outbreaks of disease reaching at times epidemic proportions. This quality of
      infectivity, or virulence, is one factor in the process but alone does not
      suffice to account for the observed facts. A second influence is not improbably
      quantity, or dosage, of the inciting microorganism. Attention to the manner of
      spread of an epidemc, as revealed graphically by the spot map, shows that it is
      never uniform but patchy. The supposition is, therefore, that among the new mice
      are certain individuals so highly susceptible as to react to small numbers of
      bacilli of average infectivity. Within these animals the multiplication is rapid,
      so that a wider spread of much larger amounts of these average, or even
      temporarily enhanced bacilli takes place with the inevitable effect of
      communicating, through greater dosage, etc., the infection to other and less
      susceptible individuals among the new and also the older lots. This process
      continues so long as rapid multiplication can occur. This latter is, in turn,
      determined by the innate tendency of the bacilli to return to an average of
      infectivity and by mouse individuals of greater resistance to restrict free
      growth and multiplication. In this manner, possibly, the epidemic spread is
      checked and the curve representing it made to fall more or less quickly to a base
      line.

PMID- 19868659
TI  - EXPERIMENTAL EPIDEMIOLOGY : INTRODUCTORY.

PMID- 19868658
TI  - EXPERIMENTS ON NORMAL AND IMMUNE MICE WITH A BACILLUS OF MOUSE TYPHOID.
AB  - If live cultures of a mouse strain of Bacillus pestis caviae are injected
      intrapleurally or intraperitoneally into normal mice, there occurs an initial lag
      in the rate of bacterial multiplication lasting a few hours, followed by a rapid
      and continued acceleration of growth until the death of the animal. If live
      cultures of this organism are given per os to normal mice, there occurs an
      incubation period of 5 to 6 days, after which the animal usually develops
      symptoms of disease and succumbs. A small percentage of mice, however, proves
      refractory to infection by this route. If live cultures of this organism are
      injected intrapleurally or intraperitoneally into mice previously "vaccinated"
      intrapleurally or intraperitoneally, they are partially destroyed and held in
      check by the protective mechanisms of the animal body for 2 or 3 days.
      Subsequently the rate of bacterial multiplication increases gradually until the
      death of the animal. The partial protection following this type of "vaccination"
      is entirely of a general nature; no evidence of a local immunity has been
      obtained. Mice given one, two, or three subcutaneous doses of "vaccine" show a
      similar relative increase in resistance to the subsequent intraperitoneal or per
      os injection of live organisms. Feeding mice live or killed cultures of this
      organism induces a definite protection against subsequent intrastomachal and
      intraperitoneal injections of live organisms. The immunity developed in this way
      is also of a general as opposed to a local nature.

PMID- 19868660
TI  - IDENTIFICATION OF A PARATYPHOID-ENTERITIDIS STRAIN ASSOCIATED WITH EPIZOOTICS OF
      MOUSE TYPHOID.
AB  - A bacillus of the paratypnoid-enteritidis group associated with epizootics among
      laboratory mice has been identified with Bacillus festis caviae Smith which
      produces similar affections in guinea pigs and has been very closely related to
      the type "mutton" aertrycke strain of Schutze. This identification is based upon
      the cultural reactions of the organism, direct and cross-agglutinations, and
      similar absorptive capacities of the unknown and type strains.

PMID- 19868661
TI  - THE LOSS OF HEMOLYTIC CAPACITY BY A FRACTION OF A CULTURE OF A HEMOLYTIC
      STREPTOCOCCUS WITHOUT CHANGE IN AGGLUTINATION CHARACTERISTICS.
AB  - A culture of hemolytic streptococcus developed a non-hemolytic fraction which as
      determined by its agglutinogenic, agglutination, and agglutinin absorotion
      characters was identical with the hemolytic fraction, the only variation being
      one of function, or physiological action. This functional variation has proved
      permanent, as long as observed, for both fractions have continued to breed true.
      This study is offered as additional evidence in favor of the hypothesis that
      functional changes among bacteria are, at most, only very infrequently associated
      with changes in the antigenic matrix of bacteria.

PMID- 19868662
TI  - THE ORGANOTROPIC, BACTERIOTROPIC, AND LEUCOCYTOTROPIC ACTIONS OF CERTAIN ORGANIC
      CHEMICALS.
AB  - We are dealing, as the results show, with groups of chemicals, all of which,
      whether bacteriotropic or not, greatly inhibit the engulfing of Staphylococcus
      aureus by leucocytes. Not a sufficiently large number of experiments was
      performed in attempt to cure experimental staphylococcus infections to warrant
      any condusion in regard to possible therapeutic activity against this organism.
      How-ever, as will appear in another paper, the only group out of the seven which
      definitely possessed an in vivo bactericidal action against pneumococcus is that
      of the cinchona derivatives. Certain members of the other chemical groups
      studied, although bactericidal in a very high dilution, -chemicals in which the
      concentration of a non-lethal dose was many times greater than that required to
      kill multiple minimal lethal doses of organisms in vitro, -had no certain effect
      when bacteria and drug were injected simultaneously into the peritoneal cavity of
      a mouse. In fact, the treated mouse often died before the controls. If we may
      assume,-leaving out of consideration the practical significance of in vivo
      chemical destruction and excretion following the injection of the drug into the
      animal,-that the failure of these chemicals to exhibit a benign influence on a
      systemic infection in cases in which the drug can be used in a bactericidal
      dilution, is due to their antiphagocytic property, only one step has been taken
      in analysis of the factors vital for the defense of the animal against a specific
      microorganism. Why do these chemicals inhibit leucocytic activity? Is it because
      of their influence upon complement, opsonin, or the leucocyte itself, or some
      special one function that determines the ability to ingest bacteria? Only further
      work can definitely settle this question and also determine whether or not such
      an analysis would be of practical importance in a rational development of
      chemotherapy. The ideal chemotherapeutic agent may be one that has an in vivo
      bactericidal potency and a negligible or stimulatory phagocytic action in doses
      non-lethal for the experimental animal. However difficult such a drug may be to
      find, it seems unlikely that the ultimate success in chemotherapy will be so
      simple. Again, it is conceivable that a secondary action of a drug, although
      leucocytotropic and not bacteriotropic, may bring about conditions in the animal
      body that will enable it to throw off the invading organism. Or finally, a drug
      compatible with the forces necessary to the host's defense and possessing in vivo
      bactericidal action to a greater or less degree may be the chemical sought for,
      the goal toward which we should strive, to achieve a rational chemotherapy for
      infectious diseases.

PMID- 19868663
TI  - THE SIGNIFICANCE OF COLOSTRUM TO THE NEW-BORN CALF.
AB  - All of ten calves which were permitted to take colostrum after birth survived.
      Eight out of twelve calves which did not get colostrum died and one was killed
      moribund. One calf, killed on the 27th day, harbored miscellaneous bacteria in
      its organs. The kidneys were sclerotic and one joint diseased. Of the remaining
      two calves, one had transitory joint troubles, the other rhinitis. One was sold
      and the other killed when 2 months old. In the latter the organs were normal and
      sterile.

PMID- 19868664
TI  - INFLUENCE OF GLANDS WITH INTERNAL SECRETION ON THE RESPIRATORY EXCHANGE : IV.
      EFFECT OF SUPRARENAL INSUFFICIENCY IN CATS.
AB  - 1. Severe and sufficient non-fatal injury to the suprarenal cortex by freezing or
      by ligation in cats causes a significant and prolonged increase in heat
      production. 2. Lethal injury to the suprarenals by freezing, ligation, or partial
      excision in cats causes a fall in heat production. 3. Insufficient injury to the
      suprarenals by freezing, ligation, or partial excision in cats produces no
      significant alteration in heat production. 4. Further evidence of a dose thyroid
      suprarenal cortex interrelationship is indicated by the rapidity of thyroid
      hyperplasia and by the effects of KI after suprarenal crippling.

PMID- 19868665
TI  - THE EXPERIMENTAL PRODUCTION OF PERIARTERITIS NODOSA IN THE RABBIT WITH A
      CONSIDERATION OF THE SPECIFIC CAUSAL EXCITANT.
AB  - 1. Periarteritis nodosa is a specific infectious disease which is transmissible
      to the rabbit. 2. The lesions induced in rabbits are identical with those
      occurring in man and consist of exudative and degenerative processes within the
      walls of the smaller arteries resulting in aneurysmal formations and thromboses.
      3. The microorganism inducing the disease is capable of going through a Berkefeld
      N filter and is therefore to be classed with the group of so called filter
      passers.

PMID- 19868666
TI  - STUDIES UPON EXPERIMENTAL MEASLES : II. THE ENANTHEMATOUS, EXANTHEMATOUS,
      PYREXIAL, AND LEUCOCYTIC SYNDROME PRODUCED IN THE RABBIT BY INTRAVENOUS
      INOCULATION OF BLOOD FROM CASES OF HUMAN MEASLES.
AB  - An active transmissible virus exists in the blood of measles patients during the
      eruptive stage of the disease. This virus produces in rabbits after intravenous
      injection a specific reaction analogous in all essential features to that of the
      human infection. Following a definite incubation period of from 2 to 5 days the
      animals infected show pyrexial, leucocytic, and cutaneous alterations. Fully 90
      per cent of such inoculated rabbits react in a remarkable manner. The earliest
      constant symptom of the infection is a rise in temperature, which on the average
      occurs 4 days after inoculation and most probably marks the end of the incubation
      period. Concomitantly with this temperature rise there is a diminution in the
      total number of circulating leucocytes. This decrease in the number of white
      blood elements may be relative or may appear in the form of a well defined
      leucopenia. The most striking objective signs are the coryza, conjunctival
      injection, enanthemata, and exanthemata. The mucous membrane lesions are similar
      in their physical appearance to the so called Koplik spots seen in man. They
      occur on the buccal side of the oral cavity ranging in number from two to eight
      discrete hemorrhagic areas with paler centers. They appear as a rule coincidently
      with the temperature rise or shortly thereafter. The exanthematous lesions though
      occurring only in about 40 per cent of the infected animals complete the clinical
      syndrome in this particular experimental host. The rash may appear as early as
      the 3rd and as late as the 7th day after inoculation. In its early stage it is of
      the macular variety, appearing as a diffuse eruption which later develops into a
      more papular type of lesion. At this time the cutaneous manifestations appear as
      slightly raised, flattened, purplish red, discrete areas in the skin of the face,
      neck, chest, and abdomen. Repeated passage of the virus of measles through the
      rabbit seems to increase its virulence. A number of animals infected with such
      passage virus succumb in the fourth and subsequent generations, undoubtedly as
      the direct result of the action of the specific excitant, as in none of the
      animals was there cultural evidence of secondary intercurrent infection. In the
      animals dying presumably as a result of the specific virus grave nephritic
      changes were evident. It is a noteworthy fact that the pneumonia so common in
      fatal cases of human measles was not evident in any of the experimental animals.
      We believe this to be of considerable significance, especially in elucidating the
      direct etiological factor of the fatal pneumonias so often present in human
      measles cases. Apparently such infections in man can be explained purely on the
      basis of the destruction of normal defense barriers by the specific excitant of
      the infectious disease, and the lack of host resistance to the ordinary pyogenic
      microorganism.

PMID- 19868667
TI  - STUDIES UPON EXPERIMENTAL MEASLES : III. THE SYMPTOM-COMPLEX IN THE GUINEA PIG
      AND RABBIT FOLLOWING THE INTRATRACHEAL AND INTRAVENOUS INJECTIONS OF FILTERED
      NASOPHARYNGEAL SECRETIONS FROM CASES OF HUMAN MEASLES.
AB  - 1. There is present as a causal agent in the nasopharyngeal secretions of measles
      cases a filter-passing virus. 2. The rabbit and the guinea pig react specifically
      to the intratracheal and intracirculatory injections of filtered nasopharyngeal
      secretions secured from cases of human measles. 3. Enanthem, exanthem, and
      pyrexial disturbances characterize this specific reaction in the rabbit; in the
      guinea pig the reaction manifests itself by pyrexia, marked leucopenia, and grave
      nephritis in the fatal cases.

PMID- 19868668
TI  - CHANGES IN THE NUMBER OF SMALL LYMPHOCYTES OF THE BLOOD FOLLOWING LIGATION OF THE
      THORACIC DUCT.
AB  - This report has attempted to analyze the changes in the absolute number of small
      lymphocytes in the blood stream of the cat following the intrathoracic ligation
      of the thoracic duct. Such a ligation produced an immediate decrease in the
      number of small lymphocytes to the extent of 56 per cent, but it was found that
      the preoperative level was again reached at about the end of 3 weeks. One is led
      to believe that the gradual return of the number of small lymphocytes to the
      preligation level took place pari passu with the establishment of the collateral
      circulation of the thoracic duct, although there is no absolute proof of this.
      Yet it is definite that the thoracic duct is an important avenue for the entrance
      of small lymphocytes into the blood stream, and that it is the pathway through
      which at least half of the small lymphocytes reach the circulating blood in the
      cat.

PMID- 19868669
TI  - THE TETANUS BACILLUS AS AN INTESTINAL SAPROPHYTE IN MAN.
AB  - 1. The only reliable method that can be used for the detection of tetanus bacilli
      is the culturing of the suspected material, the isolation of tetanus-like
      organisms and the demonstration that the pure cultures form a spasm-producing
      toxin that is neutralized by tetanus antitoxin. 2. Using this method we have
      demonstrated tetanus bacilli in 34.7 per cent of stools from 78 individuals in
      Peking. 3. The tetanus bacillus is growing in the digestive tract, for it is
      present in individuals who have been on a practically sterile diet for a month or
      more, and one individual may eliminate several million spores of tetanus bacilli
      in a single stool.

PMID- 19868670
TI  - AN EPIDEMIOLOGICAL STUDY OF RHINITIS (CORYZA) IN CALVES WITH SPECIAL REFERENCE TO
      PNEUMONIA.
AB  - During the month of November there occurred an outbreak of pneumonia among the
      calves in a large dairy. Thirty-two calves in one barn were exposed to the
      disease. Ten clinical cases developed. Two died of diffuse pneumonia. From these
      bovisepticus Group I organisms were obtained at autopsy. Four affected with
      pneumonia and eight other calves which failed to show symptoms of pneumonia
      developed a purulent rhinitis. From the nasal exudate of these cases Group I
      organisms were cultivated. The characteristic rhinitis was reproduced
      experimentally by brushing the nasal mucosa with a swab dipped in culture.
      Certain of the calves which suffered from the spontaneous rhinitis continued to
      carry the organisms in the nasal passages for periods as long as 121 days. After
      the first outbreak had subsided practically all calves introduced into this barn
      developed a milder type of rhinitis associated with organisms of Group II
      bovisepticus. 25 per cent of such calves continued to carry the organism on the
      nasal mucosa for periods of 50 to 73 days. It was possible to induce nasal
      infection in calves with pure cultures of this organism.

PMID- 19868671
TI  - MIXED CULTURES OF PURE STRAINS OF FIBROBLASTS AND EPITHELIAL CELLS.
AB  - 1. Strains of epithelium and fibroblasts cultivated side by side in the same
      medium keep their individual characteristics. When sectioned and stained by the
      Van Gieson method, the cultures show the epithelium stained greenish yellow and
      the fibroblasts and their fibrillae pink. 2. There are no transition forms
      between the epithelial cells and fibroblasts. 3. The epithelial cells belonging
      to an older strain are still able to form primitive structures of winding
      tubules, with typical glandular epithelium. 4. Under the conditions of the
      experiments, no dedifferentiation takes place.

PMID- 19868672
TI  - THE RELATION BETWEEN THE ACCUMULATION OF GLOBULINS AND THE APPEARANCE OF
      AGGLUTININS IN THE BLOOD OF NEW-BORN CALVES.
AB  - A comparison of the appearance of the agglutinins for Bacillus abortus in the
      blood of new-born calves with the first appearance of globulins in the same blood
      following the ingestion of colostrum indicates that the agglutinins are
      associated with the globulins. These observations are supported by the removal of
      the agglutinins from serum or colostrum with concentrations of sodium sulfate
      which precipitate globulins present in the blood of calves which have ingested
      colostrum, but which are not present at birth. Neither the association of immune
      bodies with globulins nor the direct absorption of protein by new-born animals is
      a new fact. The evidence presented is of particular value, however, in
      associating the appearance of certain protein fractions in the blood of the new
      born animal with the simultaneous absorption of agglutinins.

PMID- 19868673
TI  - RABBIT SEPTICEMIA BACILLUS, TYPES D AND G, IN NORMAL RABBITS.
AB  - Microbe G, rabbit septicemia bacillus, hitherto found only as a mutant in
      cultures of the rabbit septicemia bacillus, Type D, has been demonstrated to
      exist on the nasal mucous membranes of normal rabbits. This organism corresponds
      in lack of virulence, character of growth, acid agglutination optimum, and immune
      agglutination reaction, to the mutant G form described in previous papers.
      Microbe D has been found to be present on the nasal mucous membranes of normal
      rabbits. These animals have survived for months with no evidence of infection
      other than the presence of the organism. These Type D organisms, despite their
      failure to cause fatal damage in their own host, are shown to possess the typical
      high virulence characteristic of this type, when injected intrapleurally into
      young rabbits. Rabbits which are carriers of Type D or G possess a definite
      amount of immune agglutinins, as evidenced by test of their serum against Microbe
      G at pH 7.1. Rabbits free from infection with these organisms invariably have
      yielded a serum which fails to agglutinate Type G completely in 1:10 or higher
      dilutions.

PMID- 19868674
TI  - THE SOURCE OF THE MICROORGANISMS IN THE LUNGS OF NORMAL ANIMALS.
AB  - It has been possible to show that the lungs of such animals as the calf, rabbit,
      guinea pig, white rat, and white mouse are readily invaded by organisms. The most
      frequent types observed in cultures from the border of the lungs have been
      streptothrix, molds, and bacteria of the Bacillus subtilis group. These forms
      originate in certain dry food stuffs (hay and straw). By withholding or
      moistening these materials it has been possible to diminish the number of
      organisms in the lungs. When these materials have been supplied to mice whose
      lungs under usual conditions contain only a few organisms, the number of positive
      cultures increases and is comparable with those of the larger animals. The
      bronchial lymph glands of all guinea pigs examined developed, in 66(2/3) per cent
      of the tubes, organisms similar to those obtained from the lungs.

PMID- 19868675
TI  - A NEW METHOD FOR MEASURING THE PRESSURE IN THE PULMONARY ARTERY.

PMID- 19868676
TI  - EXPERIMENTAL RICKETS IN RATS : VI. THE ANATOMICAL CHANGES WHICH ACCOMPANY HEALING
      OF EXPERIMENTAL RAT RICKETS, UNDER THE INFLUENCE OF COD LIVER OIL OR ITS ACTIVE
      DERIVATIVES.
AB  - Rats which had developed rickets were treated with cod liver oil or an active
      fraction of cod liver oil, and the various changes which occur in the healing of
      the bone lesions were studied. Several phases are described, from the early
      deposit of calcium salts in the zone of preparatory calcification to the return
      to normal bone. These stages correspond closely to those found in the healing of
      human rickets.

PMID- 19868677
TI  - ETIOLOGY OF YELLOW FEVER : XIV. DURATION OF THE PROTECTIVE EFFECT OF ANTI
      ICTEROIDES IMMUNE SERUM AFTER SUBCUTANEOUS INOCULATION INTO ANIMALS.
AB  - Analysis of the records of instances in which non-immune persons contracted
      yellow fever notwithstanding vaccination shows that the onset of disease occurs
      soon after vaccination, the longest period being 13 days. Since the average
      incubation period in yellow fever is 6 days, it seems that infection must have
      taken place in some instances during the period while protection was developing.
      These instances led to a study of the possibility of immediate protection by
      means of the anti-icteroides serum. It had already been shown that the immune
      serum protects at once against experimental Leptospira icteroides infection, but
      it remained to determine how long the protection would last. Guinea pigs were
      given different quantities of the immune serum and subsequently injected, at
      various intervals, with a virulent strain of Leptospira icteroides. Complete
      protection enduring 5 days was obtained with as minute a quantity of serum as
      0.002 cc. per 1,000 gm. of body weight. After 5 days, however, the immune
      substance rapidly diminished, and to keep the animal protected for as long as 10
      days it was necessary to give 100 times as much, or 0.2 cc. For a man weighing 80
      kilos, 0.16 cc. (0.002 x 80) would theoretically be sufficient to protect for at
      least 5 days, 1.6 cc. for 7 days, and 16 cc. for 10 days. This temporary
      protection may be a valuable antecedent to that furnished by vaccination, since
      the final effect of the latter cannot be expected until at least 9 to 10 days
      have passed.

PMID- 19868678
TI  - PURE CULTURES OF LARGE MONONUCLEAR LEUCOCYTES.
AB  - 1. Pure strains of mononuclear leucocytes were isolated from the blood of adult
      chickens and keptin active condition for nearly 3 months. 2. The cultures were
      composed of large mononuclear leucocytes which migrated and proliferated in vitro
      at a slower rate than fibroblasts. The cells had no tendency to form a tissue, as
      do fibroblasts and epithelial cells. They were much less resistant than
      fibroblasts. 3. Differentiation of the large mononuclears into cells assuming the
      appearance of fibroblasts took place under certain conditions. 4. The activity of
      the large mononuclears was increased by embryonic tissue juice and inhibited by
      homologous serum.

PMID- 19868679
TI  - A PURE STRAIN OF CARTILAGE CELLS IN VITRO.
AB  - 1. A strain of cartilage cells, obtained from the pars cartilago sclerae of the
      eye of chick embryos, has been cultivated for more than 3 months in vitro. 2. The
      initial growth of the cartilage was possible only on the free surface of the
      coagulum. 3. The hyaline substance disappeared during cultivation in vitro. The
      succeeding stages of a transformation from small, lymphocyte-like cells into
      large, spindle-shaped cells were observed. The cartilage cells were spindle
      shaped and grew in close contact, forming thin membranes. In surface-grown
      cartilage cells, the nucleus, usually containing one large nucleolus, stained
      less deeply than the cytoplasm. 4. The rate of growth of cartilage was slower
      than that of fibroblasts and epithelium. After cultivation on the surface of the
      coagulum, the cartilage cells could multiply even when embedded in the coagulum.
      But their growth was less extensive and uniform.

PMID- 19868680
TI  - GROWTH-PROMOTING FUNCTION OF LEUCOCYTES.
AB  - TWO MAIN FACTS WERE BROUGHT TO LIGHT BY THE PRECEDING EXPERIMENTS: first, the
      presence of growth-activating substances in the leucocytes; second, the setting
      free of these substances in tissues and fluids where leucocytes accumulate. The
      existence of growth-promoting substances within the body of the leucocytes was to
      be expected. Leucocytes are embryonic cells and it is well known that embryonic
      tissues contain substances which stimulate cell proliferation. But the
      experiments gave a direct experimental proof of this fact. Then, during the whole
      life and even in extreme old age, there is a supply of growth-promoting
      substances within the organism which is potentially capable of restoring the
      activity of the resting cells. Embryonic tissue juice, as is known, can
      rejuvenate cells which have ceased to multiply in vitro and show evidences of
      degeneration. If the growth-activating substances of leucocytes can be
      transferred in vivo to tissue cells, they may play a similar role. Therefore, it
      was important to find out whether the growth-activating substances were set free
      either by the secretions of the living leucocytes or by diffusion from the body
      of the cells after they were injured or dead, and whether this phenomenon
      occurred actually in vivo. Indeed, the idea that leucocytes secrete substances
      necessary to normal physiological processes is by no means new. Long ago, Ranvier
      described the lymph cells as mobile unicellular glands, and Renaut thought that
      their function was to bring to fixed cells the necessary food material. This role
      of the leucocytes was considered by him as absolutely essential. According to his
      theory, differentiated cells could not live in the absence of the lymph cells,
      which supply them with the substances required for their activity. The presence
      of such substances in the leucocytes was shown by our experiments and the growth
      activating power acquired by inflamed connective tissue demonstrated that the
      leucocytes could actually bring these substances to the fixed cells. Under
      certain conditions, this property of the white cells of the blood may cause the
      resumption of the activity of tissues which are in a resting state. In the adult
      organism, the tissues have ceased to grow and the blood plasma has acquired
      marked inhibiting properties. But growth-promoting substances are still stored in
      leucocytes, glands, and muscle tissue. The leucocytes could supply fibroblasts or
      epithelial cells with the necessary food material if they were present where cell
      proliferation is needed. The existence of mechanisms causing leucocytes to invade
      tissues in need of repair is certain. The initiation of healing seems to depend
      on the coming of the leucocytes to the wounded tissue. When they are missing, as
      happens when the wound is protected from all external irritation, cicatrization
      is greatly delayed. On the contrary, when staphylococci, turpentine, and other
      irritants are applied at the surface of the wound, granulations appear after less
      than 48 hours. These irritants, although different in nature, have the common
      characteristic of determining an inflammation of the tissues and the migration of
      leucocytes from the vessels to the surface of the wound. Possibly the white cells
      bring the substances which adult tissues require in order to cicatrize or
      regenerate. They would have the function of storing away the growth-promoting
      substances characteristic of embryonic tissues, and bringing them to the regions
      of the organism where they are needed.

PMID- 19868681
TI  - CULTURES OF ORGANIZED TISSUES.
AB  - An artificial organism, if one may so term it, composed of a complex of tissues,
      was cultivated for a long period of time. Small fragments of intestine from chick
      embryos 20 to 21 days old were placed in a suitable medium. The epithelium
      proliferated and completely covered the fragment of intestine after 4 to 6 days.
      A small body was thus formed, round or oblong in shape, surrounded by cylindrical
      epithelium and containing epithelial, connective, and muscle tissues,
      endothelium, and ameboid cells. After a month's cultivation in vitro, no necrosis
      had occurred. Therefore, it may be assumed that, through the intestinal
      epithelium, the medium supplied the intestinal tissue with sufficient
      nourishment. No uncontrolled proliferation took place after the epithelium bad
      surrounded the entire fragment. The cultivation of complex tissues will
      facilitate the study of the interactions of the different cells under various
      conditions. In some experiments, pure cultures of epithelial cells were grafted
      into such an "organism" without difficulty. The growth of malignant cells could
      be studied in the same way. When the "organism" was placed in a fluid medium, the
      epithelium remained normal but the stroma disappeared. It seems that plasma
      played an important role in the maintenance of the tissues in their normal
      condition.

PMID- 19868682
TI  - ACTION OF SHAKEN SERUM ON HOMOLOGOUS FIBROBLASTS.
AB  - The preceding experiments showed that partial or complete inactivation of serum
      by shaking brought about a marked decrease in the activity of homologous
      fibroblasts. Generally, serum was not completely inactivated by shaking. In only
      one instance was the hemo-lytic effect of chicken serum on sheep corpuscles
      entirely lost after the serum had been shaken for 8 hours. In all other cases,
      the normal hemolytic power of chicken and dog sera for sheep erythrocytes was
      merely decreased. The effect of shaking varied according to certain conditions of
      the serum. It may be compared to the inffuence of heat, which differs widely
      according to individual sera, even when they are obtained from animals which are
      apparently in identical condition. Shaken serum always inhibited the activity of
      homologous fibroblasts more than normal serum. When chicken serum was completely
      inactivated by shaking, its restraining action on chicken fibroblasts became also
      more marked. On the contrary, dog serum partly inactivated by shaking was much
      less toxic for chicken fibroblasts than normal serum. Thus, shaking brought about
      a change in the condition of serum, against which homologous and heterologous
      fibroblasts reacted in an opposite manner. At the same time, the normal lytic
      action of serum on foreign erythrocytes decreased. This last phenomenon is
      caused, as is well known, by the partial or complete destruction of alexin. The
      decrease of the restraining effect of shaken serum on foreign fibroblasts may be
      attributed to the same cause. The increase of the inhibiting action of shaken
      serum on homologous fibroblasts is due possibly to the disappearance of a
      substance favoring the activity of homologous cells. A similar hypothesis was
      advanced for explaining the increase of the growth-inhibiting action of serum
      under the influence of senescence and of heat. The restraining power of adult
      serum on cell multiplication may be due to the antagonistic action of growth
      promoting and growth-inhibiting substances, the growth-promoting substance being
      as unstable as alexin and certain tissue juices which have the property of
      increasing the rate of cell proliferation. Alexin and growth-activating
      substances contained in embryonic and gland tissue juices have in common the
      property of being destroyed by heat and by shaking. Leucocytes added to serum
      under certain conditions increase its hemolytic power on foreign erythrocytes and
      decrease its inhibiting action on homologous fibroblasts. Variations in the alex
      inic activity of serum under other influences are followed also by a change in
      its action on homologous cells. Long ago, Gengou found that serum from plasma is
      less bactericidal than serum from blood. We observed that the lytic effect on
      sheep erythrocytes of dog and chicken serum from blood was sometimes more marked
      than that of serum from plasma, but there was often no difference in the action
      of both sera. At the same time, the growth of homologous fibroblasts was always
      more extensive in the serum from blood. The opposite effect was observed when
      heterologous fibroblasts were used. The growth-inhibiting power of serum from
      blood was still less marked on leucocytes than on fibroblasts. But embryonic
      juice, which greatly enhances the rate of multiplication of homologous cells, did
      not increase the lytic action of serum on foreign erythrocytes. It may be
      concluded that, under the conditions of the experiments: 1. Chicken serum partly
      or completely inactivated by shaking becomes more inhibiting for chicken
      fibroblasts. 2. Dog serum partly inactivated by shaking becomes less inhibiting
      for chicken fibroblasts.

PMID- 19868683
TI  - THE HYDROGEN ION CONCENTRATION OF JOINT EXUDATES IN RHEUMATIC FEVER AND OTHER
      FORMS OF ARTHRITIS.
AB  - 1. The hydrogen ion concentration of joint exudates aspirated from patients ill
      with acute rheumatic fever, arthritis of undetermined origin, and bacterial
      arthritis was determined. The hydrogen ion concentrations of the joint exudates
      from patients with acute rheumatic fever approximated the normal reaction of
      blood, varying from pH 7.27 to 7.42. Exudates from patients with arthritis of
      undetermined origin varied in pH from 7.33 to 7.47. The pH of a joint effusion
      occurring in a patient with myocardial insufficiency was 7.34. Bacteriologically,
      all of these fluids were sterile by ordinary means of cultivation. An exudate
      aspirated from a knee infected with Staphylococcus aureus had a pH of 6.69, while
      that from a patient having an arthritis due to Streptococcus hoemolyticus was
      also acid, having a pH of 6.19. 2. Since a definitely acid medium is necessary
      for the liberation of free salicylic acid and since all of the joint fluids from
      patients with acute rheumatic fever were slightly alkaline, no free salicylic
      acid could possibly exist in such joint fluids following the administration of
      salicylates.

PMID- 19868684
TI  - ON ALIMENTARY LEUCOCYTOSIS IN ITS RELATION TO THE "CRISE HEMOCLASIQUE" OF WIDAL.
AB  - Counts of the number of white blood cells at short intervals after the ingestion
      of a meal (meat, eggs, milk, rice, or butter) in normal individuals and in a
      number of asthmatics reveal the following facts. As a rule, a sharp fall in the
      leucocytic curve occurs within 1 or 2 minutes after the meal; generally the curve
      rises within 10 to 20 minutes, but often a second fall follows 30 to 50 minutes
      after the meal. This may be followed by a slow rise in the curve (physiological
      leucocytosis). The first sharp fall is often accompanied by a similar decrease in
      red cells, the leucocytic formula is not changed, the blood pressure also remains
      unchanged, and this makes it probable that the leucopenia observed is only a
      manifestation of a change in distribution of the blood in different regions of
      the body. Not infrequently the leucocyte curve after ingestion of food shows a
      form differing considerably from that described above. Counts of white cells made
      at intervals of 20 minutes in the same patient at different times but after
      ingestion of the same food show very different leucocytic curves. Such counts do
      not give evidence of the existence of a crise hemoclasique and consequently
      cannot be used to identify the causative agent of cases of hypersensitiveness to
      foodstuffs or drugs. Whether such an identification can be obtained if instead of
      simply counting white cells the whole complex of symptoms originally described by
      Widal as characteristic for a crise hemoclasique is used, remains undetermined by
      our work.

PMID- 19868685
TI  - EXPERIMENTAL RICKETS IN RATS : VII. THE PREVENTION OF RICKETS BY SUNLIGHT, BY THE
      RAYS OF THE MERCURY VAPOR LAMP, AND BY THE CARBON ARC LAMP.
AB  - Young rats on a diet low in phosphorus can be protected from rickets by
      irradiations with sunlight for about 15 minutes daily. In the winter months,
      however, this degree of light was found insufficient. The effective rays of the
      sun, in the intensities studied, did not penetrate window glass. They manifested
      some protective value after reflection from a smooth white surface. Irradiation
      of a few minutes with the rays of the mercury vapor lamp suffices to protect rats
      against rickets. This is true likewise of the rays from the carbon arc lamp. A
      standard protective dose of radiation can be formulated for rats on a standard
      diet. Light is able to prevent the occurrence of rickets in rats fed a rickets
      producing diet characterized either by a low phosphorus and high calcium content,
      or a high phosphorus and low calcium content. Moderate variations in temperature
      do not alter the effective action of light rays. Pigmentation of the skin
      markedly lessens their effect, as demonstrated by the failure of a standard dose
      to protect black rats.

PMID- 19868686
TI  - EXPERIMENTAL RICKETS IN RATS : VIII. THE EFFECT OF ROENTGEN RAYS.
AB  - Rats on a low phosphorus diet cannot be protected from the development of rickets
      by exposures to soft Roentgen rays such as were employed in this study.
      Furthermore, rats on a diet containing phosphate in an amount adequate to prevent
      rickets were not rendered rachitic by exposure to massive doses of Roentgen rays
      of an intensity sufficient to produce marked destruction of the blood-forming
      cells of the marrow.

PMID- 19868687
TI  - COW SERUM AS A SUBSTITUTE FOR COLOSTRUM IN NEW-BORN CALVES.
AB  - The serum of a normal lactating cow when injected into calves a few hours after
      birth saved only two out of five calves so treated. Serum added to the milk of
      the first two meals saved three out of five. When the two methods were combined
      and the serum was both injected and fed all five calves so treated survived as
      normal calves. These figures to be significant should be compared with the
      controls of both series. Since the beginning of this investigation twelve out of
      thirteen colostrum-fed calves have survived and only four out of fifteen from
      which colostrum has been withheld. In those that died the serum whether fed or
      injected protected the internal organs against the invasion and multiplication of
      Bacillus coli and other intestinal types and in this respect its protective
      action is equivalent to that of colostrum in those calves which die of
      spontaneous scours.

PMID- 19868688
TI  - THE IODINE CONTENT OF THE BLOOD FOLLOWING THYROIDECTOMY.
AB  - 1. After thyroidectomy in dogs the iodine content of the blood is increased. 2.
      The administration of fresh thyroid gland of sheep by mouth to thyroidectomized
      dogs causes the iodine content of the blood to fall so that it returns to the
      normal preoperative level; when the thyroid feeding is discontinued the iodine
      content of the blood is again increased.

PMID- 19868689
TI  - BLOOD DESTRUCTION DURING EXERCISE : I. BLOOD CHANGES OCCURRING IN THE COURSE OF A
      SINGLE DAY OF EXERCISE.
AB  - The following changes have been demonstrated to take place in the blood of dogs
      during exercise. 1. An increase in the per cent of cells and hemoglobin in the
      blood of the jugular vein occurs early in the course of exercise. It probably
      results from a redistribution of red corpuscles, with an increase in their
      proportion in the peripheral blood. 2. As exercise is continued, there is a
      definite increase in plasma volume. 3. A coincident decrease both in the total
      cell volume and the pigment volume during prolonged exercise suggests that blood
      destruction then occurs.

PMID- 19868690
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      IX. THE RECURRENCE OF 1922.
AB  - From the nasopharyngeal secretions of patients in the early hours of
      uncomplicated epidemic influenza during the recurrence in New York City in
      January and February, 1922, we have again obtained an active agent, pathogenic
      for rabbits, and have identified this active agent as Bacterium pneumosintes.
      Four new strains of this micro-organism have been isolated in pure culture and
      identified with the 1918-19 and 1920 strains on morphological, cultural, and
      serological grounds. All of the significant characteristics of the old strains,
      including their effect upon the resistance of the lungs of rabbits to secondary
      invasion with other bacteria, have been noted in the new strains, which thus have
      served to confirm and extend our original observations.

PMID- 19868691
TI  - DIFFERENCES BETWEEN MITOCHONDRIA AND BACTERIA.
AB  - A direct comparison of mitochondria and bacteria in the living condition, as well
      as in permanent preparations, subjected to the same influences, and viewed side
      by side, reveals microchemical and tinctorial differences which can only be
      attributed to a fundamental dissimilarity in their chemical constitution.

PMID- 19868692
TI  - ACTION OF ANTIGEN ON FIBROBLASTS IN VITRO. II.
AB  - The action of human ascitic fluid and of dog serum on the immunization of
      fibroblasts in vitro was investigated. The toxic effect of ascitic fluid upon
      fibroblasts was slight, while that of dog serum was marked. When a small amount
      of antigen (1.5 to 2 per cent dog serum, or 8 per cent ascitic fluid) was present
      in the medium, the resistance of the fibroblasts slowly increased, reached its
      maximum after about 14 days, and gradually decreased. The curve expressing the
      phenomena closely resembles that of Jorgensen and Madsen showing the production
      of antibodies in an animal which received daily injections of antigen. When the
      antigen was present in the medium in a high concentration (from 5 to 8 per cent
      dog serum), the resistance reached its maximum in 4 days, and decreased rapidly.
      It may be concluded that: 1. In the immunization of fibroblasts in vitro against
      a foreign protein, there is a relation between the amount of antigen, the time of
      the appearance of immunization, and its duration. 2. When a small amount of
      antigen is used, immunization slowly reaches its maximum, and slowly decreases.
      3. When a large amount of antigen is used, immunization reaches its maximum in a
      short time, but the protection is of equally short duration.

PMID- 19868693
TI  - SURFACE TENSION OF SERUM : IV. ACTION OF TEMPERATURE.
AB  - 1. The surface tension of pure serum, heated at 55 degrees C., decreases
      progressively and regularly until the serum coagulates. A drop of 8.2 dynes was
      observed in 168 hours. The mean drop was 5.7 dynes in 120 hours and 4 dynes in 96
      hours. 2. The initial surface tension of solutions of serum at the concentrations
      10(-1) up to 10(-6) is practically not affected by heat, but the time-drop in 2
      hours is modified. 3. Each serum seems to react in its own particular way as far
      as the time-drop is concerned. However, there is a general tendency for the
      solution to show an increase of time-drop at the concentrations 10(-1), 10(-2),
      10(-3) and 10(-5), and a decrease at 10(-4), when heated at 55 degrees C. a
      decrease of the time-drop at the concentrations 10(-1), 10(-2) and 10(-3), and an
      increase at 10(-4) when heated at 100 degrees C. 4. Nevertheless, only the
      changes observed below 10(-3) are constant in sign, within 75 or 80 per cent of
      the cases. The concentration 10(-4) seems to correspond to a state of greater
      instability. This confirms the hypothesis of the existence of a monomolecular
      layer at that concentration, which was assumed on the basis of the existence of a
      maximum drop at 10(-4). Should this be true, and provided the principle of Gibbs
      could be transformed so as to be applicable to mixed solutions of colloids and
      crystalloids, an idea of the size, or at least of one of the dimensions of the
      molecules or group molecules composing the serum could probably be obtained. 5. 1
      drop of the solutions at 1:10 evaporated on glass and examined under the
      microscope shows the marked differences brought about by heating at different
      temperatures.

PMID- 19868694
TI  - INVESTIGATIONS ON THE OXYGEN CONTENT OF CUTANEOUS BLOOD (SO CALLED CAPILLARY
      BLOOD).
AB  - 1. A procedure is devised whereby cutaneous blood (so called capillary blood)
      from a finger-tip can be obtained for gas analyses without coming in contact with
      the air. 2. Determination was made of the oxygen content of the arterial,
      cutaneous, and venous blood respectively from a normal resting individual, the
      arterial and cutaneous blood showing the same oxygen content (97.5 and 96.6 per
      cent of the total oxygen-combining power of the blood). Venous blood drawn
      simultaneously was 75 per cent saturated. 3. Using the fact that there is a
      maximum value for the oxygen-combining power of the blood, we have shown, without
      doing arterial puncture, that under different conditions (normal and pathological
      individuals, resting and after exercise) the cutaneous blood and the arterial
      blood are almost identical as far as the oxygen content is concerned. 4. We think
      that we are justified in extending the identity, found between the oxygen content
      of the arterial and cutaneous blood, to other substances in the blood, for
      instance sugar, salt, uric acid, etc., and also to the reaction of the blood. 5.
      We are unable to say whether this identity between cutaneous and arterial blood
      is always true; for example, in a patient with increased venous pressure. 6. In
      all the experiments we have discarded the first drop of blood, which in some
      instances was darker than the rest, and always used at least 2 cc. of cutaneous
      blood. Whether the same results would be obtained with a very small amount of
      blood, for instance 0.2 to 0.4 cc., we do not know. 7. The experiments show that
      unless the perfusion of the skin has been extremely great during the experiment,
      samples of blood obtained from an incision in the skin (of the finger) cannot
      represent the true capillary blood. The neutral expression cutaneous blood seems
      therefore for the present preferable to the term capillary blood for samples of
      blood obtained by cutaneous incisions.

PMID- 19868695
TI  - STUDIES ON THE BIOLOGY OF STREPTOCOCCUS : II. ANTIGENIC RELATIONSHIPS BETWEEN
      STRAINS OF STREPTOCOCCUS HAEMOLYTICUS ISOLATED FROM SCARLET FEVER.
AB  - 1. Hemolytic streptococcus has been found in 100 per cent of the throats of
      patients with scarlet fever during the 1st week of the disease. 2. The average
      length of time that these organisms are present in the throat varies from 10 to
      20 days. 3. No morphological or cultural characteristics peculiar to the
      hemolytic streptococcus from scarlet fever can be demonstrated. 4. Ten immune
      sera have been prepared from different strains of scarlet fever streptococci and
      each of the sera agglutinated more than 80 per cent of the strains isolated from
      scarlatinal throats. On the other hand, scarlatinal streptococci are not
      agglutinated by immune sera prepared from hemolytic streptococci isolated from
      other pathological sources. 5. Serum from patients convalescent from scarlet
      fever agglutinates weakly or not at all the homologous strain of hemolytic
      streptococcus. 6. The specificity of the agglutination reaction of scarlatinal
      streptococci is confirmed by absorption experiments. 7. Scarlatinal
      antistreptococcic serum affords some degree of protection against virulent
      scarlet fever streptococci but has no protective power against hemolytic
      streptococci from other diseases. 8. In a small epidemic of scarlet fever a
      healthy carrier of hemolytic streptococcus was detected; the organism carried was
      identical in its serological reactions with strains of hemolytic streptococci
      isolated from active cases of scarlet fever. 9. In a study of a number of
      contacts with a case of scarlet fever, in only one instance was a scarlatinal
      type of hemolytic streptococcus recovered from the throat.

PMID- 19868696
TI  - STUDIES ON ENDOTHELIAL REACTIONS : VI. THE ENDOTHELIAL RESPONSE IN EXPERIMENTAL
      TUBERCULOUS MENINGOENCEPHALITIS.
AB  - 1. Experimental cerebral and meningeal tubercles in the rabbit are formed from
      cells of endothelial origin. 2. These cells are derived apparently from other
      sources than the neighboring capillary endothelium alone. 3. The circulating
      macrophages, which, in this case, are capable of multiplying by mitosis while
      still free in the blood, are drawn upon in the formation of the cerebral
      tubercle. 4. Splenectomy has not materially decreased the available supply of
      circulating macrophages in this experiment. 5. While these cells may originate in
      the endothelium of the liver and bone marrow, the lung appears to play a much
      more important role in this respect than has been hitherto suspected.

PMID- 19868697
TI  - SPIROCHAETA EURYGYRATA : A NOTE ON ITS LIFE HISTORY AND CULTIVATION.
AB  - 1. Pure lines of Spirochoeta eurygyrata were isolated and cultured. 2. They lived
      longest in a medium which was made up of sodium chloride and pig serum water. 3.
      They stained readily with iron-hematoxylin, Giemsa's stain, Cross' stain, and
      carbolfuchsin. 4. They did not stain with the vital dyes used. 5. They divide by
      transverse division. 6. Transverse bars, which are seen in stained spirochetes
      and in dead ones with dark-field illumination, are considered coagulated
      protoplasm, due to death. 7. Coccoid bodies were not seen in living individuals
      nor were they seen free in the culture medium. 8. Cats were fed cultures of
      Spirochoeta eurygyrata but did not become infected with them. 9. Spirochoeta
      eurygyrata is not of frequent occurrence in this part of the United States.

PMID- 19868698
TI  - INSUSCEPTIBILITY TO SENSITIZATION AND ANAPHYLACTIC SHOCK.
AB  - 1. Attempts to produce anaphylactic shock in white rats by second intravenous or
      subdural injections of horse serum have failed. 2. It was impossible to
      demonstrate either by skin reactions or by the uterine reaction that white rats
      can be sensitized to horse serum. 3. It was not possible to sensitize guinea pigs
      passively with the serum of white rats presumably immunized to horse serum. 4. In
      spite of the fact that the white rat could not be made anaphylactic to horse
      serum, the tissues of the animal reacted with the horse serum to form precipitins
      in fair concentration and the antigen disappeared from the circulation soon after
      the precipitins reached their greatest concentration in the blood. 5. These
      experiments would indicate that in the white rat anaphylaxis and precipitin
      formation are independent and represent different types of immunological
      processes.

PMID- 19868699
TI  - LEUCOCYTIC SECRETIONS.
AB  - In the present condition of the technique of cultivation of tissues, the only
      possible way of studying leucocytic secretions was to grow colonies of leucocytes
      in a medium of known properties and to examine the modifications of these
      properties under the influence of the living cells. The method was far from
      perfect, because the secretions were mixed with serum and accumulated for 48
      hours in a medium where they probably underwent partial destruction. But an
      approximate idea of certain of the qualities of the secretions, although not of
      their quantity, could be derived from the experiments. In the fluids extracted
      from the cultures, we attempted to detect the presence of the leucocytic
      secretions through their physiological effects on homologous and foreign cells.
      Two kinds of substances were sought, those which act on homologous cells, and
      those which destroy foreign erythrocytes. The secretion by leucocytes of
      substances necessary to the nutrition of other cells was considered as probable
      long ago. Renaut thought that the main function of the white blood corpuscles was
      to bring to the fixed cells of the tissues the food material which they need.
      While the existence of physiological relations between leucocytes and tissue
      cells could be considered as almost certain, their nature had remained
      practically unknown. It was probable, however, that the substances secreted by
      leucocytes were analogous to the growth-activating and unstable substances which
      are found in embryonic tissues, leucocytes, and certain adult tissues. When
      connective tissue was aseptically inflamed, or when an aseptic peritoneal exudate
      contained many leucocytes, aqueous extracts of both connective tissue and
      peritoneal exudate were found to have acquired the power of stimulating cell
      proliferation. These experiments showed that leucocytes could bring to the
      tissues some activating substances. But it remained to be ascertained whether
      leucocytes, while they are alive, could secrete similar substances either
      spontaneously or under the stimulus of a foreign factor. Leucocytes are supposed
      to be, as is well know, the origin of the substances which protect the organism
      against infection. Although the problem of the origin of alexin and antibodies
      has been investigated by many experimenters, it is not yet completely solved. It
      was of interest, therefore, to ascertain whether leucocytic secretions could
      increase the natural hemolytic effect of hen serum on sheep or rabbit
      erythrocytes, and whether these secretions would become more active under the
      influence of a foreign protein. The substances which destroy foreign cells are
      not necessarily different from those which act on homologous cells. The word
      substance is used for simplicity of description and may be taken as meaning only
      a given property of an unknown substrate. A comparison was made of certain
      properties of sera extracted after 48 hours incubation from media containing
      leucocytes and from media containing no leucocytes. The serum from the leucocytic
      cultures was always found to be more favorable to the growth of homologous
      fibroblasts than the serum from the culture media incubated without leucocytes.
      The natural hemolytic power of the serum on sheep erythrocytes was found to be
      increased in about SO per cent of the experiments. In other experiments, we found
      that when two culture media free of cells were placed, one in an incubator at +38
      degrees C. and the other in a refrigerator at +5 degrees C. for 48 hours, the
      serum from the incubated medium partly lost its hemolytic action on sheep or
      rabbit erythrocytes, while that from the refrigerated medium remained normal; at
      the same time, the inhibiting action of the incubated medium on homologous
      fibroblasts had increased very much. This effect of incubation indicates that
      certain unstable constituents of serum are destroyed by heat. Then the changes
      found in the properties of the serum from cultures of leucocytes are due to the
      fraction of the activating substances which has not been destroyed by incubation
      at 38 degrees C. A quantitative study of the secretions is, therefore, impossible
      with the present technique, which can furnish only qualitative indications about
      the substances set free by the leucocytes. We have ascertained also whether a
      medium containing leucocytes and kept in the refrigerator undergoes any change
      under the influence of the cells while they are in a condition of latent life.
      Gabritschewski dishes with and without leucocytes were placed in a refrigerator
      at a temperature of about +5 degrees C. After 48 hours, the hemolytic power on
      sheep erythrocytes of the serum from the leucocytic cultures had increased
      slightly and its inhibiting action on the growth of homologous fibroblasts had
      decreased. Then certain substances favorable to the growth of homologous cells
      and toxic for heterologous cells were diffused by the leucocytes into their
      medium. But the action of these substances was weaker than in the case of the
      cultures kept in the incubator. This experiment showed that leucocytes under
      certain conditions diffuse alexin or natural hemolysins which originate from them
      at the same time as the substances which activate homologous cells. In other
      experiments, although leucocytes were frozen at -10 degrees C., treated with
      distilled water, or extracted with saline solution, they did not yield any
      hemolysin. To summarize: Leucocytes, cultivated in plasma, always secreted
      substances which increased the rate of growth of homologous cells. Less
      frequently, they set free substances which hemolyzed foreign erythrocytes. The
      growth-promoting substances are analogous to those contained in embryonic
      tissues, and probably represent some of the foodstuffs brought to fixed tissue
      cells by leucocytes. They may possess the function of rejuvenating cells which
      have ceased to multiply when the cicatrization of a wound or the repair of a
      fracture requires a resumption of tissue activity. According to this hypothesis,
      the leucocytes brought to the surface of a wound by the process of inflammation
      would not only oppose bacterial invasion, but also bring to the tissues the
      material necessary to cell multiplication. It seems that in some cases
      regeneration is started by substances brought to the tissues by other cells. Loeb
      thinks that in Tubularia, when endodermic cells gather at the end where a new
      polyp is about to be formed, the substances given off by these cells are
      responsible for polyp formation.(6) There may be an analogy between this
      phenomenon and the secretion by leucocytes of growth-activating substances at the
      surface of a wound. If we assume that leucocytes in vivo set free their
      secretions in the blood stream, certain variations of the growth-inhibiting
      action of normal serum can be better understood. The rate of proliferation of
      homologous fibroblasts is much slower in the serum of an old chicken than in that
      of a young one. When the serum is heated at 56 degrees and 70 degrees C. for
      (1/2) hour, it becomes still more inhibiting. A substance favorable to cell
      activity has disappeared. It is therefore permissible to suppose that the growth
      inhibiting power of serum and its variations are due to the antagonistic action
      of two substances, one growth-promoting and thermolabile, and the other growth
      inhibiting and thermostable, the activating substance being always weaker in its
      effect than the inhibiting one. We know that activating substances can be
      extracted from embryonic tissue, from muscle and gland tissues, and from
      leucocytes of the adult animal, and that they are thermolabile and very unstable.
      Leucocytic secretions seem to have some of the properties of leucocytic extracts.
      It is probable that the activating substances which disappear from the heated
      serum are secreted by leucocytes and other cells. An increase of these
      secretions, then, would diminish the inhibiting action of serum on homologous
      fibroblasts. On the contrary, a decrease of the secretions in the serum would
      increase its inhibiting effect on homologous cells. The strong inhibiting action
      of serum in old age would be due partly to a reduction in the amount and activity
      of the substances secreted by leucocytes and tissue cells in the humors of the
      organism. Leucocytes also secreted in vitro substances which were toxic for
      foreign cells. Although the results were not constant, the serum appeared to
      become slightly more hemolytic for sheep or rabbit erythrocytes, under the
      influence of the leucocytes. The hemolysis of rabbit corpuscles by hen serum is
      due, according to Hyde,(9) to a complex sensitizer alexin, and not merely to
      alexin, as Bordet thought. When a foreign protein was added to the culture
      medium, the leucocytic secretions increased, as was shown by the action on
      homologous fibroblasts of sera taken from cultures of leucocytes with and without
      casein. The presence in the medium of the cultures of leucocytes of only 0.1 per
      1,000 casein did not markedly modify the action of their serum on the
      proliferation of fibroblasts. When the concentration of casein in the leucocyte
      cultures reached 1 per 1,000, the growth of chicken fibroblasts in the serum
      extracted from the Gabritschewski dishes became more rapid. But there was no
      parallel increase of the hemolytic action of the serum upon sheep erythrocytes.
      We found that chicken serum containing 0.1 per 1,000 casein was barely toxic for
      homologous fibroblasts, while it became markedly inhibiting when the casein
      concentration reached 1 per 1,000. Probably, there is a relation between the
      toxicity of the medium, the increase of leucocytic secretions, and the time of
      the increase. The change brought about by casein in the equilibrium of the system
      composed of the cells and their medium determines the secretion by the leucocytes
      of substances which increase the activity of homologous cells and oppose the
      inhibiting effect of the foreign proteins. (ABSTRACT TRUNCATED)

PMID- 19868700
TI  - THE LOSS OF CIRCULATING ERYTHROCYTES IN CERTAIN TYPES OF EXPERIMENTAL PNEUMONIA.
AB  - Erythrocyte counts, blood volume, hemoglobin, and hematocrit determinations on a
      series of dogs suffering from experimental pneumonia induced by the tracheal
      insufflation of Bacillus bronchiseplicus and Bacillus mucosus capsulatus indicate
      that in this condition there is an actual loss of circulating erythrocytes,
      without compensatory regeneration. Postmortem examination of the organs of these
      animals revealed red cells in various stages of degeneration in the capillaries
      and tissue spaces of the lungs, liver, spleen, and intestinal walls.

PMID- 19868701
TI  - THE SUPRAVITAL STAINING OF VACCINE BODIES.
AB  - Vaccine bodies in living corneal cells may be specifically stained by the
      addition of a small quantity of brilliant cresyl blue 2 B to the physiological
      salt solution in which they are being observed. Their appearance by this method
      (Figs. 3 to 17) corresponds with that seen in fixed preparations (Figs. 22 to
      42). Both lines of study reveal the existence of traces of similar material in
      unvaccinated corneal cells. As this increases in amount during the reaction, it
      behaves like an integral, cytoplasmic constituent of fluid consistency and shows
      no evidence of being endowed with any measure of independent vitality. The low
      grade of structural differentiation which it does exhibit, in living cells as
      well as in fixed tissues, is not suggestive of the presence within it of
      independent microorganisms. The material differs radically in its morphology and
      microchemical reactions from the granules observed by MacCallum and Oppenheimer
      in vaccine lymph.

PMID- 19868702
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      X. THE IMMUNIZING EFFECTS IN RABBITS OF SUBCUTANEOUS INJECTIONS OF KILLED
      CULTURES OF BACTERIUM PNEUMOSINTES.
AB  - A series of rabbits was subcutaneously injected with three measured doses of
      killed cultures of two strains of Bacterium pneumosintes derived from the
      nasopharyngeal secretions of influenza patients. These rabbits were subsequently
      tested for the development of serum antibodies and for the presence of an induced
      immunity to the living organisms, with the following results. The serum of eleven
      of fifteen rabbits, tested from 10 to 27 days after the final subcutaneous
      injection, specifically agglutinated Bacterium pneumosintes, whereas normal
      rabbit serum did not. Nineteen vaccinated rabbits were subjected to protection
      experiments. Two of them were unaffected by an intratracheal injection of
      Bacterium pneumosintes, contained in the lung tissues of previously infected
      animals, in a dose which typically affected the control rabbits. Fifteen of the
      other seventeen proved to be completely resistant when tested by intratracheal
      injections of Bacterium pneumosintes cultures that produced typical infections in
      the controls. Ten of these fifteen rabbits were injected intravenously with
      living cultures of pneumococcus, Streptococcus hamolyticus, or Bacillus pfeifferi
      in doses which were non-infective under normal conditions, but infective, as
      experience has shown, in the presence of a primary lesion caused by Bacterium
      pneumosintes. In none of these animals did infection develop. The two remaining
      rabbits of the seventeen were not protected against Bacterium pneumosintes by the
      vaccination, and they further developed a secondary pulmonary infection with
      Bacillus pfeifferi after its intravenous injection. Control rabbits similarly
      injected intratracheally with Bacterium pneumosintes, and then intravenously with
      the pneumococcus, streptococcus, or Bacillus pfeifferi in doses that had proved
      non-infective for normal rabbits, uniformly developed a secondary infection with
      these organisms. The mildness of the local reactions and the absence of general
      signs, following vaccination with Bacterium pneumosintes, indicate that similar
      injections would be well tolerated in man. There is no evidence that the
      subcutaneous injection of large doses of the heat-killed organisms reduces the
      resistance of the animal body to infections with other bacteria. In single rabbit
      experiments the resistance to intravenously injected pneumococci, streptococci,
      or Bacillus pfeifferi has been found unreduced immediately after vaccination with
      Bacterium pneumosintes.

PMID- 19868703
TI  - STUDIES ON THE DISEASE OF GUINEA PIGS DUE TO BACILLUS ABORTUS.
AB  - 1. The infectivity of Bacillus abortus for guinea pigs is extremely great. It is
      computed that somewhat less than 100 organisms are required to infect most
      animals. 2. Occasional animals are encountered having much more resistance to
      Bacillus abortus infection than is possessed by the average. The most resistant
      animal encountered was infected by a number of organisms computed to be less than
      10,000. 3. The principal effect on the character of the Bacillus abortus disease,
      caused by varying the size of the infecting dose, is a change in the time
      relations. Very small doses produce an infection of slower course than do larger
      doses, but the eventual results are practically the same. 4. Judging by the
      agglutination curves, guinea pigs inoculated with large or medium sized doses of
      Bacillus abortus generally begin to gain mastery over the disease about the 10th
      week after inoculation. At this time the agglutination curve begins to decline.
      As was first shown by Smillie, the numbers of bacteria in the body organs begin
      to decline at about the 4th week but the change is rather slow until about the
      10th or 12th week when a rapid decline begins, coincidently with the fall in the
      agglutinin titer. When the inoculating dose is small the course of the disease
      may be much prolonged. The defensive forces of the body would appear to be quite
      inactive until a certain stage in the disease is reached. 5. The virulence of
      Bacillus abortus cultures for guinea pigs may be raised or lowered by appropriate
      passage through these animals. 6. Normal guinea pig blood will not agglutinate
      Bacillus abortus in a dilution of 1:10. Immune agglutinins are easily produced by
      inoculations with dead or living organisms. Agglutinins for Bacillus abortus are
      capable of passing the placental filter. 7. There appears to be little or no
      danger of normal guinea pigs becoming infected by association with diseased
      animals of their own sex. One instance is reported, however, of the infection of
      a male animal that had cohabited with infected females. 8. The susceptibility of
      guinea pigs to infection through ingestion of Bacillus abortus is relatively
      slight.

PMID- 19868704
TI  - THE VALUE OF HEAT-KILLED CULTURES FOR THE PREVENTION OF THE BACILLUS ABORTUS
      INOCULATION DISEASE OF GUINEA PIGS.
AB  - From the data presented it seems permissible to draw the following conclusions.
      1. Guinea pigs cannot be rendered immune to the Bacillus abortus inoculation
      disease by treatment with heat-killed cultures of this organism. This agrees with
      the work of Ascoli, and with the general conclusions of many that dead cultures
      confer very little or no immunity to infectious abortion in cattle. 2. The
      progress of the disease can be delayed appreciably by such treatment. This is
      supported by the following observations: (a) the loss in body weight due to the
      disease is delayed; (b) the development of splenic enlargement is partially
      inhibited or delayed; (c) the development of renal lesions is delayed or
      prevented; and (d) the rapidity of multiplication of Bacillus abortus in the
      splenic pulp is reduced.

PMID- 19868705
TI  - THE SUSCEPTIBILITY OF MICE AND RATS TO INFECTION WITH BACILLUS ABORTUS.
AB  - 1. White mice are highly susceptible to infection by inoculation with Bacillus
      abortus. The susceptibility appears to be as great as that of the guinea pig, and
      this animal probably can be substituted satisfactorily for guinea pigs in
      diagnostic work. 2. Both mice and rats are very refractory to feeding infection
      with Bacillus aborlus. The failure to infect mice in this way was complete, but
      the feeding of large amounts of culture gave infection in rats. Subcutaneous
      inoculation resulted in infection of all the animals. The difficulty of infecting
      rats and mice with Bacillus abortus by feeding makes it very doubtful whether
      these animals can have any role in the propagation and spread of infectious
      abortion in cattle.

PMID- 19868706
TI  - THE ACTION OF SODIUM SALICYLATE UPON THE FORMATION OF IMMUNE BODIES.
AB  - 1. Rabbits treated with sodium salicylate in daily doses of from 0.16 to 0.2 gm.
      per kilo of body weight and at the same time immunized with intravenous
      injections of Streptococcus viridans, both living and in the form of vaccines,
      and also with washed sheep red blood cells, showed diminished complement-fixing
      antibodies, agglutinins, and hemolysins when compared with controls similarly
      immunized. 2. If the antigens were treated with sodium salicylate in vitro and
      subsequently injected intravenously into rabbits, the animals usually showed
      lower antibody curves than did rabbits that received the untreated antigen
      intravenously and sodium salicylate by stomach tube. 3. The beneficial effect of
      sodium salicylate in rheumatic fever patients probably cannot be attributed to an
      increased production of circulating immune bodies against the infectious agent.
      This is, however, no contraindication to the administration of salicylates to
      patients suffering from infectious diseases.

PMID- 19868707
TI  - THE REVERSE SELECTIVE BACTERIOSTATIC ACTION OF ACID FUCHSIN.
AB  - 1. Acid fuchsin possesses a bactericidal power, selective as between Gram
      negative and Gram-positive spore-bearing aerobic organisms. The selective feature
      is the reverse of that of gentian violet. 2. This reverse selective activity is
      also possessed by simpler sulfonated substances and would appear to be dependent
      in some way on the presence of SO(3) radicals. 3. Selective penetration, if at
      all concerned in the behavior of gentian violet and acid fuchsin toward bacteria,
      must play a very minor role. 4. In the case of gentian violet the power to kill
      organisms and the power to prevent their growth run, so far as the selective
      feature is concerned, parallel. In the case of acid fuchsin, the bacteriostatic
      and bactericidal selective features do not run parallel. 5. Bacillus pyocyaneus,
      an organism resistant to gentian violet, is quite susceptible to acid fuchsin.
      This organism is the cause of annoying and persistent infections in wounds. The
      observations on the effect of the sulfonated substances may give a lead as to the
      control of these infections.

PMID- 19868708
TI  - A METHOD FOR THE PERMANENT STERILE DRAINAGE OF INTRAABDOMINAL DUCTS, AS APPLIED
      TO THE COMMON DUCT.
AB  - The sheath of omentum that forms about a long rubber tube left within the
      peritoneal cavity provides so efficient a barrier to ascending infection that
      such a tube can be employed for the permanent drainage of the common duct,
      whereas a short tube will regularly come away after a few days. A method is
      described whereby the total bile of a considerable number of dogs has been
      obtained in a sterile state during periods up to 3 months. Save for some anemia,
      the animals remained in good health throughout. The method has obvious uses in
      connection with the collection of other secretions.

PMID- 19868709
TI  - BLOOD DESTRUCTION DURING EXERCISE : II. DEMONSTRATION OF BLOOD DESTRUCTION IN
      ANIMALS EXERCISED AFTER PROLONGED CONFINEMENT.
AB  - A great decrease in total circulating hemoglobin and red cell volume occurs in
      dogs long maintained under sedentary conditions when they are exercised
      vigorously during several consecutive days. This would appear to be consequent on
      increased blood destruction, unrepaired for the time being.

PMID- 19868710
TI  - THE INTESTINAL FLORA IN MOUSE TYPHOID INFECTION.
AB  - The normal flora of laboratory mice at The Rockefeller Institute, fed on a bread
      and milk diet, was determined. Bacillus acidophilus and Bacillus bifidus
      outnumber the Bacillus coli, Bacillus acidi lactici, and Bacillus coli communior
      group about twenty-five to one. White and yellow cocci which may or may not
      liquefy gelatin are occasionally noted; spirochetal and vibrio forms and yeasts
      are usually seen in stained preparations. This flora does not change when mice
      are artificially infected per os with a strain of mouse typhoid bacilli (Bacillus
      pestis cavice) and is the same in the animals which resist the infection as in
      those which succumb. Mice fed on a meat diet and showing a colon, Bacillus
      diffluens, and Bacillus welchii flora do not differ in susceptibility to mouse
      typhoid from the normal mice fed on bread and milk and showing the above
      acidophilus flora.

PMID- 19868711
TI  - OX BILE SENSITIZATION IN MOUSE TYPHOID INFECTION.
AB  - Sterile ox bile, administered per os in maximum doses to laboratory mice, tends
      to increase their susceptibility to mouse typhoid infection.

PMID- 19868712
TI  - A NEW METHOD FOR MAMMALIAN DECEREBRATION.

PMID- 19868713
TI  - THE ACTION OF DRUGS ON RESPIRATION : I. THE MORPHINE SERIES.
AB  - 1. A method is described for recording intrathoracic pressure in cats without
      opening the pleural cavity; active expiratory movements were elicited by
      inhalation of a constant CO(2)-air mixture for a given time and a study was made
      of the action of drugs on inspiration and expiration. 2. Morphine and heroine
      were found to exert a selective depressant action on the central expiratory
      mechanism, and the slower rate, with relatively unaltered depth, seemed to be due
      at least partly to the slower rate of emptying the lungs. Codeine had no
      depressant action on the respiration of decerebrated cats. 3. Larger doses of
      morphine or heroine had no further depressant effect on rate or depth of
      breathing after expiration was made passive, unless circulatory depression
      appeared, and failure of circulation seemed to be the cause of respiratory
      depression, rather than the reverse relation. In decerebrated animals large doses
      of morphine and moderate doses of codeine stimulated the spinal cord, and
      expiration became active, with a faster rate of breathing. The characteristic
      action of morphine and heroine on the respiration of the cat is apparently
      limited to a depression of active expiration.

PMID- 19868714
TI  - THE ACTION OF DRUGS ON RESPIRATION : II. ETHER, CHLOROFORM, CHLORAL, URETHANE,
      LUMINAL, MAGNESIUM, CAFFEINE, STRYCHNINE, AND ATROPINE.
AB  - 1. The depressant drugs which have been studied in this series of experiments
      were found to resemble morphine and heroine in that they depressed expiration
      more than inspiration, but they acted only in narcotic doses and always depressed
      inspiration at the same time. Ether caused a sharp expiratory rhythm, persisting
      until narcosis was very deep, probably a result of irritation of the air
      passages. Chloroform sometimes caused dyspnea, even in very deep narcosis,
      probably because of circulatory depression. Hydrated chloral made respiration
      more rapid, but shallower. Urethane usually made expiration active, often with
      inspiratory pauses, such as may follow vagotomy. Magnesium seemed to produce the
      most uniform, uncomplicated depression of all the depressants tried. Luminal
      resembled morphine and heroine more closely than any of the general depressants,
      making expiration passive without depressing inspiration, but it acted only in
      narcotic doses, unlike morphine and heroine. 2. Caffeine and strychnine, whenever
      they caused acceleration after morphine, brought back active expiration. Atropine
      never stimulated, and commonly acted as a synergist to morphine. 3. It is
      suggested that the results outlined in this and the preceding paper point to the
      existence of a separate central mechanism for the control of each of the phases
      of respiration, and that, while each responds to the same chemical stimuli, the
      threshold of the expiratory is higher than that of the inspiratory. Evidence is
      presented to indicate that if expiration remains passive a marked increase in
      depth of breathing may slow the rate, and a respiratory mechanism that lacks
      active expiration may be so inefficient that a CO(2) concentration which
      stimulated when expiration was active may depress when it is passive.

PMID- 19868715
TI  - A FUNCTIONAL AND ANATOMICAL STUDY OF THE EXCRETION OF HEMOGLOBIN BY THE KIDNEY.
AB  - 1. The anatomical and functional findings in hemoglobin excretion are best
      explained by the assumption of a filtration of this substance through the
      glomerulus and an additional excretion of it by the tubule cells. 2. Absorption
      of water aids in the concentrating process, and is most marked in the collecting
      tubules.

PMID- 19868716
TI  - THE MECHANISM OF THE VOMITING INDUCED BY ANTIMONY AND POTASSIUM TARTRATE (TARTAR
      EMETIC).
AB  - 1. It has been shown that tartar emetic acts on the stomach to induce emesis
      after its oral administration, that only traces are present in the vomitus
      following its intravenous injection (Kleimann and Simonowitsch), and that it does
      not induce emesis when it is applied directly to the vomiting center (Thumas). 2.
      In the present study, which was made with cats except when otherwise specifically
      stated, the intravenous injection of tartar emetic caused emesis (typical
      vomiting movements) after the removal of the entire gastrointestinal tract from
      the esophagus to the anus. 3. Cutting the vagi inhibits emesis after the
      intravenous injection of any dose of tartar emetic, though nausea may be induced.
      4. Cutting the vagi and simultaneously extirpating the stellate ganglia inhibits
      both nausea and vomiting after the intravenous injection of tartar emetic. 5.
      Extirpation of the celiac ganglion and simultaneous cutting of the vagi just
      below the level of the diaphragm does not prevent emesis following the
      intravenous injection of tartar emetic. 6. Cutting the vagi prevents vomiting
      after the introduction of large doses of tartar emetic into the stomach, but
      massive doses may still cause emesis. Vagotomy probably has less influence on the
      emetic action of a moderately large dose of tartar emetic introduced into a loop
      of the duodenum. 7. Atropine has very nearly the same effect on the emetic action
      of tartar emetic as cutting the vagi, but much larger doses are necessary to
      abolish the effect of the introduction of tartar emetic into the stomach in
      moderate amounts than that of equal amounts injected intravenously. 8. The facts
      just stated point to the heart as the seat of reflex vomiting following the
      intravenous injection of tartar emetic. 9. The intravenous injection of tartar
      emetic induces afferent emetic impulses which pass from the heart to the vomiting
      center mainly by way of the vagus, to a much less extent by way of the
      sympathetic nerve and the stellate ganglia. 10. The introduction of tartar emetic
      into the stomach induces afferent emetic impulses which pass upward mainly by way
      of the vagus, to a much less extent by way of the sympathetic nerve. 11. The
      introduction of tartar emetic into the duodenum induces afferent emetic impulses
      which pass upward partly by way of the sympathetic nerve, partly by way of the
      vagus. 12. It seems probable that the path taken by afferent emetic impulses
      induced in the gastrointestinal tract by tartar emetic depends on the innervation
      of the organ concerned, and not on any selective action of the poison on the
      afferent nerve.

PMID- 19868717
TI  - INFLUENZA-LIKE BACILLI ISOLATED FROM CATS.
AB  - Six strains of Gram-negative non-motile bacilli from cats have been described.
      They do not grow on ordinary media. They do grow, however, on a medium to which
      an autoclave-labile substance alone has been added as an accessory growth factor.
      These bacilli are similar to Bacillus parainfluenzaaeisolated from man. One
      strain of a Gram-negative non-motile bacillus more exacting than Bacillus
      influenzae in its food requirements was found and for convenience has been placed
      for the present in the parainfluenza group.

PMID- 19868718
TI  - STUDIES ON ENDOTHELIAL REACTIONS : VII. CHANGES IN THE DISTRIBUTION OF COLLOIDAL
      CARBON NOTED IN THE LUNGS OF RABBITS FOLLOWING SPLENECTOMY.
AB  - THE CHANGES IN THE DISTRIBUTION OF INTRAVENOUSLY ADMINISTERED COLLOIDAL INK IN
      SPLENECTOMIZED RABBITS MAY BE INTERPRETED SOMEWHAT AS FOLLOWS: The removal of the
      spleen throws an increased amount of ink into the other hematopoietic organs and
      the lung and liver. While we should expect the liver or the bone marrow to
      compensate for the loss of the spleen and to take up this ink and remove it from
      the circulation, that is not the case. The lungs appear to play the chief part in
      the process, slowly passing on the removed material, contained in macrophages, to
      the liver, or retaining these ink-laden cells in their tissues and capillaries.
      By an increase in the capillary endothelium and by a process of engorgement of
      the capillaries with cells presumably derived therefrom, the lungs remove by far
      the greater part of the foreign material that has been introduced into the
      circulation. At the same time there is an increase in the number of ink-bearing
      macrophages in the lymphatics and capillaries of the lung, indicating that these
      cells are entering the circulation and the lymph stream (Fig. 8). The only organ
      where they lodge in any quantities, outside of the peribronchial lymph nodes, is
      the liver, the sinusoids of which contain an increasing number of macrophages as
      time goes on. It is possible that these cells are destroyed in the sinusoids and
      the carbon transferred to the liver epithelium; there is evidence to support this
      assumption. After the lungs, the liver comes next in degree of intensity of
      pigmentation; the bone marrow contains far less than either of these organs.

PMID- 19868719
TI  - THE SOURCE OF AGGLUTININS IN THE MILK OF COWS.
AB  - The foregoing experimental cases point to a distinct participation of the udder
      in the production of agglutinins when the gland is invaded by living or flooded
      by dead bacteria. The quarter injected reacts at first with a heavy influx of
      polynuclear leucocytes and later with an increase of agglutinins.

PMID- 19868720
TI  - CHLORIDE RETENTION IN EXPERIMENTAL HYDRONEPHROSIS.
AB  - 1. In acute experimental hydronephrosis chloride retention occurs as well as
      retention of water, urea, and phenolsulfonephthalein. 2. If both water and
      chlorides are retained there may be no appreciable rise in the plasma chloride
      content. 3. When chlorides are retained, but not water, the chloride content of
      the plasma rises strikingly. 4. After the removal of the ureteral obstruction in
      acute hydronephrosis all renal functions, water, urea, and chloride excretion,
      may be rapidly restored in equal degree, or the chlorides may be retained
      temporarily while there is free excretion of water and urea. 5. In chronic
      hydronephrosis adequate daily excretion of urea and chlorides may be maintained
      by a compensatory polyuria. 6. Chloride retention or an abnormal chloride
      excretion may occur in certain renal lesions when there is no change in the urea,
      phenolsulfonephthalein, or water excretion.

PMID- 19868721
TI  - BLOOD DESTRUCTION DURING EXERCISE : III. EXERCISE AS A BONE MARROW STIMULUS.
AB  - A definite increase in the percentage of reticulocytes occurs after exercise in
      animals previously kept to a sedentary life. Concomitant changes in the
      hemoglobin percentage, plasma-cell ratio, and red count offer evidence in
      addition to that already reported by the author of the occurrence of an increase
      in blood destruction under such circumstances. Replacement by transfusion of
      blood destroyed during exercise prevents the reticulated cell reaction. Animals
      rendered plethoric and then exercised show no increase in reticulated cells while
      the plethora persists. The fact is emphasized that exercise must be an important
      factor in the maintenance of an efficient hematopoietic tissue.

PMID- 19868722
TI  - BLOOD DESTRUCTION DURING EXERCISE : IV. THE DEVELOPMENT OF EQUILIBRIUM BETWEEN
      BLOOD DESTRUCTION AND REGENERATION AFTER A PERIOD OF TRAINING.
AB  - Animals recently caged do not show as large a decrease in cell volume after
      exercise as those which have been confined several months. When a dog kept for a
      long time under sedentary conditions is exercised continuously for several weeks,
      a decrease in cell volume occurs in the 1st or 2nd week of exercise, but usually
      by the end of the 3rd week the loss has been made up. Apparently by this time the
      hematopoietic tissues have adapted themselves to the increased demands made upon
      them by the hastened rate of destruction. There is, furthermore, some anatomical
      evidence that such is the case.

PMID- 19868723
TI  - A CYTOLOGICAL STUDY OF THE NATURE OF RICKETTSIA IN ROCKY MOUNTAIN SPOTTED FEVER.
AB  - The Rickettsia of Rocky Mountain spotted fever were easily differentiated from
      mitochondria, phagocytosed blood pigment, nuclear debris, and all other known
      cellular constituents. Although they were lodged within the cytoplasm of
      endothelial cells, they were not observed to establish any definite relations
      with the nucleus or with other cellular components. Their number varied in
      contiguous cells which sustained the same degree of injury as evidenced by
      nuclear changes, and alterations in their mitochondria content. The mitochondria,
      on the other hand, showed similar modifications, characterized by a decrease in
      number and a rounding up into spherules, in all the endothelial cells seen in a
      section of an affected blood vessel. Diplobacillary forms were most abundant in
      the early stages of the reaction and single bacillary bodies towards its
      termination. Other slight differences in morphology from Wolbach's account were
      noted in the organisms as seen in the tissues of both ticks and guinea pigs. His
      study of the distribution of specific lesions with accompanying organisms in the
      tissues of guinea pigs was confirmed and extended.

PMID- 19868724
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN MOUSE TYPHOID INFECTION.
AB  - Mice bred at The Rockefeller Institute vary in their susceptibility to mouse
      typhoid infection caused by a certain strain of Bacillus pestis caviae. This
      graded variation may be roughly analyzed as follows: in any series infected per
      os with a fixed dose, 20 to 30 per cent show no sign of infection, no positive
      blood cultures, and no agglutinins; 5 or 10 per cent present symptoms of disease,
      positive blood cultures, and then recover with or without homologous agglutinins;
      70 or 80 per cent develop positive blood cultures and succumb in a more or less
      constant ratio relative to time. The strain of Bacillus pestis caviae employed
      throughout a 10 month series of experiments has shown no permanent change in
      virulence. Blood cultures taken from infected mice early in disease, shortly
      after death, and 6 days after death, chronic stool carrier cultures, and chronic
      septicemia cultures, all show approximately the same degree of virulence.

PMID- 19868725
TI  - CONTRIBUTION TO THE MANNER OF SPREAD OF MOUSE TYPHOID INFECTION.
AB  - The experiments reported in this paper and in the preceding one indicate that
      with a given susceptible mouse population and a certain strain of mouse typhoid
      bacilli the sporadic and epidemic prevalences of mouse typhoid are determined by
      the spacial and quantitative distribution of the bacilli. Under circumstances in
      which the entire mouse population is so exposed as to be in direct contact with
      an infecting dose of the mouse typhoid bacillus, the nature of the resulting
      mortality curve depends upon the quality of susceptibility of the individuals
      composing the population.

PMID- 19868726
TI  - FURTHER STUDIES ON BACTERIAL HYPERSUSCEPTIBILITY. II.
AB  - When filtered alkaline extracts of pulverized bacteria of several varieties are
      precipitated with acid in the cold, boiled with acid, and all materials thrown
      down by these procedures removed, there remains a small amount of an alcohol
      precipitable material which no longer gives any of the ordinary chemical
      reactions for proteins, such as the biuret, Hopkins-Cole, Millon, and
      sulfosalicylic acid reactions. The only protein reaction usually given by this
      material is a very weak xanthoproteic reaction. Nevertheless, the material, which
      is, as far as we can determine at present, free from coagulable protein, is
      specifically precipitable by homologous antiserum and gives specific complement
      fixation reactions. Such material can also be obtained from organisms like the
      influenza bacillus, pneumococcus, and meningococcus by extraction without
      preliminary grinding of the bacteria, and is present in filtrates of young and
      old broth cultures of the organisms. We believe that these acid- and heat
      resistant antigenic materials are analogous to tuberculin and to the pneumococcus
      substances with which Dochez and Avery (6) made their observations some years
      ago. The stability of these substances is considerable and was investigated
      particularly because we thought this represented an indirect method of
      eliminating the possibility of their protein nature. In all cases boiling in a
      reflux condenser at an acid reaction ranging from pH 5 to 6 for 1 hour failed to
      destroy the antigenic specificity of the residue antigens. After such treatment
      satisfactory and specific precipitation reactions could be obtained. Similar
      boiling in alkaline reactions, however, destroyed the precipitability of
      staphylococcus and influenza residues. Subjected to autoclave digestion at an
      acid reaction of pH 5.4 for 1 hour at from three to four atmospheres, none of the
      antigenic residues investigated, except that obtained from the influenza
      bacillus, were destroyed. The pneumococcus and tubercle bacillus residue antigens
      were resistant to boiling for 1 hour, both in acid and alkaline reactions (pH 5.4
      and 9.4). In fact, none of the procedures resorted to made any difference with
      these two last mentioned substances. It would seem that these facts would add
      considerable weight to the assumption that the materials dealt with were not
      ordinary whole proteins. On preservation in the ice box at an alkaline reaction
      of pH 9.4, the influenza residue deteriorated within 48 hours, but the other
      antigens withstood similar treatment for 6 days. In spite of the fact that these
      residue antigens were precipitable by homologous sera produced by immunization
      with the whole bacteria or their unfractionated extracts, we have so far failed
      to produce antibodies in animals by injecting these residues. While this may be
      due to inability to inject sufficient amounts of the material it still suggests
      strongly the possibility that we may be dealing with substances that are
      antigenic only in the sense that they are able to react with antibodies, but are
      themselves incapable of inciting antibody production. We suggest, in this
      connection, the possibility of the relationship between the power of antibody
      production and molecular size. This phase of the work is being continued on a
      more extensive scale. Our work on the reactions of the residue materials in
      infected animals indicates, as far as we have gone, that complete analogy exists
      in this respect between the conditions prevailing in guinea pigs infected with
      these organisms and those previously elucidated for tuberculous animals. This is
      in keeping with previous knowledge concerning the analogies between the mallein
      and tuberculin reactions and the studies on skin hypersusceptibility in Bacillus
      abortus- and typhoid-infected guinea pigs reported by Meyer and his coworkers. It
      would seem from all these facts that, in guinea pigs infected with bacteria
      capable of forming foci in the body, infection is followed within a variable, but
      relatively short time (5 days to 2 weeks) by a type of hypersusceptibility which
      is distinct from protein anaphylaxis and which may be determined by intradermal
      skin reaction. It appears likely that the growing bacteria elaborate in the
      animal body a metabolic product, possibly not a whole protein, which, though
      practically non-toxic to normal animals, may become highly and specifically
      injurious to the infected ones. Such a conception, if further confirmed, would
      lead to greater clearness in our comprehension of the toxic effects occurring in
      infections with organisms not true exotoxin producers and, judging by the
      cellular injuries observed in severe skin reactions, may easily explain focal
      necrosis and the deeper cellular degenerations observed in the course of many
      bacterial diseases. The general bearing of this work upon conceptions of
      hypersusceptibility is obvious and has been briefly discussed in another paper.
      Its chief significance is in holding out the hope that we may be able to
      elucidate the mechanism of a type of specific hypersusceptibility in which the
      antigen concerned is not a coagulable protein and in which the laws of
      sensitization in regard to time and quantity differ from those recognized in true
      protein anaphylaxis. It seems likely that a recognition of the fact that physical
      and chemical differences in the substances leading to various forms of specific
      hypersusceptibilities in the animal body must necessarily influence the mechanism
      of sensitization, may furnish a clue to further investigations. As such materials
      become simpler in structure, they fail to induce typical antibody production and
      by gradually increased diffusibility transfer the reactions from the cell surface
      to the interior of the cell. The extremes of the scale of differences would be
      represented by protein anaphylaxis, on the one hand, and drug idiosyncrasies, on
      the other. Although this suggestion is largely speculative, it has seemed worth
      mentioning as a line of reasoning suggested by our work. Incidentally, these
      studies may indicate the usefulness of the residue antigens for specific
      precipitation and complement fixation reactions for routine purposes in
      laboratory investigations.

PMID- 19868727
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      XI. ANTIBODIES IN THE BLOOD AFTER RECOVERY FROM EPIDEMIC INFLUENZA.
AB  - Although Bacterium pneumosintes is a stable organism which agglutinates only in
      low dilutions of the serum of actively immunized rabbits, the serological
      reactions of this microorganism have always been found to be consistent and
      specific. The results of the agglutination and precipitation reactions described
      in this paper indicate that the serum of normal persons does not contain
      demonstrable agglutinins or precipitins for Bacterium pneumosintes. By contrast,
      agglutinins have been demonstrated in the serum of seventeen persons among
      nineteen who were examined from 10 days to 5 months after recovery from epidemic
      influenza. The serum of ten persons who had influenza, followed in three
      instances by pneumonia, 2(1/2) to 3(1/2) years before, proved negative. In one
      instance the appearance of specific agglutinins against Bacterium pneumosintes
      was found to be coincident with an attack of uncomplicated influenza. In twelve
      of fifteen instances in which agglutinins were found, precipitins against
      Bacterium pneumosintes were demonstrated also. It is noteworthy that these
      antibodies may persist in the blood at least 5 months after recovery from the
      disease.

PMID- 19868728
TI  - THE CULTIVATION OF ANAEROBIC TREPONEMATA ON THE SURFACE OF BLOOD AGAR PLATES.
AB  - By a method of cultivation that proved successful with Bacterium pneumosintes,
      characteristic surface colonies of old saprophytic strains of Treponema pallidum
      and Treponema calligyrum have been obtained. The presence of two types of colony
      in the pallidum cultures requires explanation, but the fact of colony formation
      may point the way to new methods of isolation and identification and to the
      utilization of suspensions of treponemata, free from foreign proteins, for
      serological and immunological purposes.

PMID- 19868729
TI  - STUDIES ON THE CHANGES PRODUCED BY ROENTGEN RAYS IN INFLAMED CONNECTIVE TISSUE.
AB  - The action of x-rays upon inflamed tissue manifests itself in the first place by
      a considerable depression of the usual reaction on the part of the fibroblasts.
      Under normal circumstances these elements begin to divide mitotically during the
      first 24 hours and soon form a layer of new connective tissue, surrounding the
      foreign body. After treatment with x-rays they remain idle, do not multiply at
      all, or start very late and often the division is abnormal. They undergo a high
      degree of pathological hypertrophy of protoplasm and nucleus. Instead of mitosis
      often amitotic constrictions appear in the nucleus. The capacity for collagen
      formation seems also to be lost. Simultaneously with these changes of the
      fibroblasts an intensive edema of the connective tissue surrounding the foreign
      body is to be noted and in the immediate neighborhood of the latter a thick layer
      of net-like clotted fibrinous exudate is formed. No distinctive qualitative
      changes could be found in the leucocytes and polyblasts. Degeneration was present
      here only to the same extent as in common aseptic inflammation. But first the
      rate and the duration of the emigration of all the cells coming from the blood
      were increased, and secondly there was always a distinct delay in the process of
      the common transformations usually undergone by the polyblasts on the field of
      inflammation. The transformation of the polyblasts into fixed resting forms seems
      above all to be delayed. Therefore, even in late stages, the tissue is
      overcrowded with granular special leucocytes and with mostly young, lymphocyte
      like polyblasts, whereas in the early stages the local resting wandering cells
      only slowly undergo mobilization. Furthermore, in the blood vessels swelling of
      the endothelial cells with fragmentation of the nuclei and, in the striated
      muscles, degeneration of the fibers can be detected. In the latter there occur
      partly typical coagulation necrosis, partly atrophy, accompanied by loss of
      striation, separation of fibrillae from one another, relative increase of
      sarcoplasm, and amitotic division of nuclei. What the ultimate result of all
      these changes would be, is as yet not clear. In the case of longest duration, in
      which 60 days had elapsed since the last exposure, no distinct difference could
      be found between the exposed and control preparations. Thus one might believe
      that the cell injuries caused by the x-rays, and above all the inability of the
      fibroblasts to multiply and to elaborate collagen, are again repaired in due
      time. However, my material is decidedly inadequate in this respect and several
      cases of long duration should be examined. It is surprising that the results
      obtained seem not to agree with the predominating views on the action of x-rays
      on cells. Apart from the endothelium of the blood vessels, of all the cells
      present in the field of inflammation the fibroblasts undoubtedly are to be
      considered as the elements most highly differentiated in a specific sense. I have
      shown that, as a rule, they do not round up in inflammation and do not produce
      ameboid cells, but remain unchanged in morphology and, through mitotic division,
      give rise to the new connective tissue. On the other hand, there can be no doubt
      that the lymphocytes and the polyblasts are to be looked upon as relatively
      indifferent cells, endowed with great prospective potencies of development. Thus
      it might be expected that just the lymphocytes of the inflamed area would be
      affected in the first place by the rays, as they are in the blood-forming organs,
      and that the fibroblasts, on the contrary, would be refractory. But the facts
      have proved that the most conspicuous and constant changes concern the
      fibroblasts. They are paralyzed for a long time and made unable to build up new
      tissue. The fibrinous exudate and the edema might perhaps also depend partly on a
      direct injury of the colloidal intercellular substance, partly on changes of the
      endothelium of the blood vessels, cells which are again to be considered as
      highly differentiated. Noteworthy signs of degeneration could not be found in the
      lymphocytes and polyblasts. But here again the necessary early stages 1 to 3 days
      after the last exposure were not available; it is possible that the emigrated
      lymphocytes are destroyed by the x-rays rapidly, in an explosive manner, in 24 to
      48 hours, as in the lymph nodes or the thymus, or as described by Pautrier in the
      chronically inflamed tissue of the skin in mycosis fungoides. Their remains might
      be quickly resorbed and after the last exposure new lymphocytes would have time
      to emigrate out of the blood vessels and to pass to the tissue. However, if we
      take this for granted, there remains another inexplicable fact, concerning the
      local resting wandering cells-their close genetic relationship with the
      lymphocytes is beyond doubt and yet exposure to x-rays does not seem to affect
      them. In this connection it may be stated that Soper found that the reticulo
      endothelial apparatus, whose cells correspond to the resting wandering cells, is
      stimulated by small doses of x-rays and paralyzed by large doses. For deciding
      these problems further investigations are necessary. The classical researches of
      O. Hertwig and his school have proved beyond doubt that of all the parts of the
      cell, the nucleus with its chromatin is affected most by the rays. It is believed
      that the nuclei in mitotic division are especially sensitive (Holthusen) and that
      the nuclei of exposed cells lose, in the first place, their capacity for normal
      mitosis; they either do not undergo division at all or they show pathological
      mitoses (Grasnick, Gaskell, and others). The observations described above fully
      coincide with these statements. The nuclei of the hypertrophied fibroblasts
      attain an enormous size, contain an abnormal amount of chromatin, are sometimes
      vacuolated, and appear paralyzed and incapable of mitosis or divide abnormally.
      Perhaps the reason that the fibroblasts in the present experiments are so
      strongly affected by the x-rays is that they are the only cells which are
      preparing for mitotic division directly after the introduction of the foreign
      body, whereas the lymphocytes and polyblasts only rarely divide in the field of
      inflammation. The fibroblasts thus are becoming especially sensitive towards the
      rays, whereas for example in the scar tissue, where they remain quiescent, they
      are not affected. As the inflammatory changes in the normal skin after exposure
      to x-rays are not known sufficiently from the histological standpoint it would be
      promising to study the action of x-rays on the normal loose connective tissue. It
      is evident that the changes in the cells of the inflamed area, chiefly in the
      fibroblasts, but also in the muscle fibers, under the influence of Roentgen rays,
      are the result of complicated interrelations between two different agents, first,
      the inflammation stimulus, and, second, the radiant energy. Neither agent alone
      in the doses used is able to produce the changes observed. Only the combination
      of both gives the results described above. It seems to be immaterial, to a
      certain degree, which of the two stimuli is applied first-whether the foreign
      body be introduced in previously exposed tissue, or the latter be exposed after
      the introduction of the body-in both cases practically the same results have been
      obtained. The strong inhibitory and deleterious influence of x-rays on inflamed
      connective tissue ought to be always kept in mind in the therapeutical use of
      this kind of energy, especially in cases of malignant tumors, in which the local
      connective tissue in most cases is found in a state of inflammatory irritation.

PMID- 19868730
TI  - FURTHER STUDIES ON THE ETIOLOGICAL SIGNIFICANCE OF VIBRIO FETUS.
AB  - The general outcome of these six experimental cases and those already reported is
      that both motile and non-motile types produce disease of the fetal membranes
      eventually leading to abortion. The more precise serological relations between
      the two are now under investigation.

PMID- 19868731
TI  - THE INCREASED ABSORPTION OF X-RAYS BY VITALLY STAINED WHITE RATS.
AB  - The object of this investigation was to test out the sensitizing effect of
      various vital stains upon rat tissues in the presence of x-ray energy. For the
      purposes of the experiment, it had been found that a dosage of See PDF for
      Equation at 50 kilovolts induced death in white rats within 110 to 120 hours.
      This amount of energy was selected as a tentative standard for the experiments.
      The preliminary injection of small amounts of such stains as trypan blue in 0.5
      per cent aqueous solution sensitized the rat tissues to such an extent that the
      period of viability of these rats after administration of the standard dosage of
      x-ray energy, was shortened to from 60 to 70 hours. The cause of death in the
      stained rats has not been ascertained despite careful histologic study.
      Considerable variation in the susceptibility of rats to the combined procedure
      was noted.

PMID- 19868732
TI  - CHEMICAL CHANGES IN THE BLOOD OF THE DOG AFTER INTESTINAL OBSTRUCTION.
AB  - A study of the non-protein nitrogen, urea nitrogen, uric acid, creatinine, amino
      acid nitrogen, sugar, and chlorides of the blood and the CO(2)-combining power of
      the plasma in normal dogs, and in dogs after different types of intestinal
      obstruction, is reported. Following ligation of the duodenum, ligation of the
      duodenum with gastroenterostomy, and ligation of the upper half of the ileum, a
      fall in chlorides and a rise in the non-protein nitrogen and urea nitrogen of the
      blood and in the CO(2)-combining power of the plasma occur. The uric acid,
      creatinine, amino-acid nitrogen, and sugar show no significant changes. The
      fundamental change is a fall in chlorides followed by an alkalosis. The degree of
      alkalosis depends upon the rate of formation of carbonate, rate of excretion by
      the kidneys, and extent of neutralization of the carbonate by acid bodies formed
      during the intoxication. The fall in chlorides is probably due to a utilization
      of the chlorine ion in the course of the intoxication. It is suggested that this
      use of chlorine is a protective measure on the part of the body. There are
      indications that high intestinal obstruction should not be treated by the
      administration of alkalies. The urea nitrogen is a good index of the protein
      destruction. Ligation of the ileum at the ileocecal valve is followed by little
      increase in nitrogen and no change in the chlorides or CO(2)-combining power of
      the plasma. The close similarity of the blood findings in intestinal obstruction,
      acute lobar pneumonia, and serum disease suggests that these widely different
      conditions may have a common chemical basis.

PMID- 19868733
TI  - CHEMICAL CHANGES IN THE BLOOD OF THE DOG AFTER PYLORIC OBSTRUCTION.
AB  - Chemical studies of the blood and urine of four dogs following pyloric
      obstruction are reported. The observations of other workers that a fall in
      chlorides and a rise in CO(2)-combining power of the plasma occur, are confirmed.
      There is also a marked rise in the non-protein nitrogen of the blood, consisting
      mainly of urea nitrogen and undetermined nitrogen. The fall in chlorides is not
      due to the loss of chlorides in the gastric juice. The chlorine is probably bound
      somewhere in the process of protein destruction. There is a close relation
      between the fall in chlorides and the protein destruction. A study of tetany
      should include the protein metabolism as well as that of the inorganic salts,
      since it seems possible that the tetany is due to protein split-products and not
      to the alkalosis. The chemical changes following pyloric obstruction are
      essentially the same as those following high intestinal obstruction.

PMID- 19868734
TI  - IMMUNITY STUDIES OF ROCKY MOUNTAIN SPOTTED FEVER : I. USEFULNESS OF IMMUNE SERUM
      IN SUPPRESSING AN IMPENDING INFECTION.
AB  - From the results of the experiments presented it is evident that in guinea pigs
      an early administration of immune rabbit serum will suppress the infection; that
      is, if it is given within the period of incubation, the effect being
      proportionately greater the earlier the serum is administered. Almost no
      beneficial effect is observed when the serum is given after the onset of the
      disease. In the animals inoculated with 10 to 100 M.L.D. the incubation period is
      shorter than when 1 M.L.D. is injected; nevertheless 1 cc. of the immune serum
      saved the animals as late as 96 hours from the time of the introduction of the
      virus into the system. When administered within 24 hours in the case of 100
      M.L.D. and within 48 hours in the case of 10 M.L.D., the serum completely
      neutralized the virus, and the animals escaped infection altogether. On the other
      hand, the same quantity of the serum only modified the infection into a non-fatal
      one when given a day or two later. In the animals which were inoculated with 1
      M.L.D. the incubation period was a day or two longer, and the neutralizing effect
      of the serum was much more powerful. Here animals were saved as late as 5, 6, and
      7 days and with a much smaller quantity of the serum (0.1 cc.). As to the
      usefulness of such an immune serum in human cases, the relative susceptibility of
      man and the guinea pig must first be considered. In a large number of
      experimental infections carried out with guinea pigs in the past 6 years almost
      never has a naturally refractory animal been encountered. The mortality is nearly
      80 per cent with most strains, although as low as 50 per cent with some. The
      strain used in the present study caused death in nearly 80 per cent of the
      animals. Hence the susceptibility of guinea pigs is at least as great as that of
      man, in whom the mortality in the Bitter Root Valley is estimated to be about 70
      per cent. The relative length of the incubation period in guinea pig and in man
      is another point which requires analysis. In guinea pigs it varies somewhat
      according to the number of passages, being as short as 3 days when 100 M.L.D. or
      more of an adapted virus are inoculated. On the other hand, when the infection is
      the result of 1 M.L.D. or the bite of an infected tick, the incubation period is
      much longer, being 5, 6, or 7 days in the former and 7 to 8(1/2) days in the
      latter instance, as with the present strain. In man the infection is brought on
      by the bite of an infected tick, and the period of incubation varies from 3 to 10
      days but is usually 7 days; i.e., it is about the same as in guinea pigs infected
      with 1 M.L.D. Hence we may regard the susceptibility of man and the guinea pig as
      nearly equal. The final point to be considered is the quantity of the immune
      serum that may be recommended for use in human cases. To prevent the infection in
      a guinea pig weighing 500 gm., 0.1 cc. of the serum was sufficient. This quantity
      protected the animal against 1 M.L.D. even as late as 5, 6, or 7 days. Calculated
      on this basis, 16 cc. of the serum would be required for a man weighing 80 kilos
      (about 160 pounds); that is, 16 cc. of an immune rabbit serum, administered
      before onset of the disease, should theoretically be sufficient to save a man of
      average weight against an infection brought about by the bite of an infected tick
      or by a laboratory accident. It would probably be best to administer the serum
      intravenously. The titer of the immune serum should be previously determined in
      guinea pigs, and 1 cc. should neutralize 100 M.L.D. completely and 0.1 and 0.01
      cc. render the infection non-fatal. Such a serum is easily produced in rabbits (a
      rabbit weighing 2,500 gm. will yield 50 to 60 cc. of the serum) and probably will
      remain active a year or longer when kept at refrigerator temperature.

PMID- 19868735
TI  - STUDIES ON THE TOTAL BILE : I. THE EFFECTS OF OPERATION, EXERCISE, HOT WEATHER,
      RELIEF OF OBSTRUCTION, INTERCURRENT DISEASE, AND OTHER NORMAL AND PATHOLOGICAL
      INFLUENCES.
AB  - By a method of permanent intubation the entire output of bile from dogs has been
      obtained in a sterile state over long periods of time, and studied
      quantitatively. The secretion of the first few days after the initial operation
      is scanty, contains more pigment than that secreted later, and is sometimes so
      viscid as to cause temporary obstruction within the collecting tube. The small
      amount and thick consistency of the fluid are referable to direct injury of the
      liver and ducts, while the abundant bilirubin is derived, in part at least, from
      the hemoglobin of extravasated blood. In some animals in which there was
      accidental mercuric chloride poisoning at the time of operation a suppression of
      the bile followed which, in one instance, was complete during the 48 hours before
      death. In a dog developing mixed infection of the biliary tract, an almost
      colorless fluid, glairy as white of egg, gradually took the place of the bile.
      Not until a week or 10 days after operation does the bile acquire the character
      which it maintains later. The quantity of this later bile, as measured in
      successive 24 hour specimens, is greatly less than that recorded by previous
      investigators, a difference attributable to disturbing influences inevitable to
      the method of collection they employed. By our method, it averaged from 3.5 to
      9.5 cc. per kilo of dog in 24 hours, though transient variations from 1 cc. up to
      14 cc. were encountered. Some dogs give consistently far more bile than others.
      The frequently recorded effects of fasting to lessen the rate of secretion, and
      of a meat diet to increase it more than a carbohydrate one, were noted often.
      Contrary to expectation, vigorous exercise does not act to increase the quantity
      of the bile. During hot weather this may sink greatly, although the animal
      remains in good condition; and during intercurrent diseases unassociated with
      jaundice, the flow may almost cease. One of the best of cholagogues, bile by
      mouth, fails of effect under such circumstances. It acts best when the animal is
      healthy, the weather not oppressive, and the food intake abundant. The bilirubin
      output, after the immediate effects of the operation have worn off, remains
      nearly constant from day to day, though often exhibiting slow, wave-like
      variations, each extending over a week or more. These slow changes are
      synchronous with similar alterations in the hemoglobin percentage of the
      circulating blood. A recognition of them is important to studies of the bilirubin
      yield. A mild anemia, absent in controls maintained under like conditions,
      regularly develops in unexercised dogs completely deprived of bile, despite their
      apparent health, and as it does so the bilirubin output falls off. Prior to the
      development of the anemia the output averages about 7.5 mg. per kilo in 24 hours,
      a yield which closely corresponds with that recorded by previous workers.
      Vigorous exercise of animals previously sedentary causes an increased pigment
      output presumably as result of increased blood destruction. Since the daily
      pigment output is approximately constant, whereas the fluid quantity undergoes
      frequent and great changes, it follows that the pigment concentration must vary
      inversely as the fluid quantity, and vary greatly. It does both. No matter how
      large or small the 24 hour specimen of bile may be within "normal" limits,
      therein will be found the customary quota of pigment. When, under pathological
      conditions, the bile flow almost ceases, the pigment concentration becomes
      extremely great. A similar reciprocal relationship between concentration and
      fluid quantity would seem to hold for the mucinous element of the bile. Scanty
      biles are ropy as a rule, and copious ones are watery. Temporary obstruction was
      produced by clamping the outlet tube from the common duct, and the bile yield
      following upon its relief was studied. Secretion was for a time far more copious
      than usual, with a low pigment content per cubic centimeter, and tended to remain
      so until the accumulated pigment had been voided. As much extra bilirubin is put
      forth after 24 hours of obstruction as if the liver continued to manufacture the
      pigment without interruption during it. Obstruction for this length of time
      appears to cause no subjective disturbance in most instances, though
      bilirubinuria develops. Even this sign of bile retention may be lacking when
      obstruction endures but 12 hours. The physiological and clinical significance of
      these facts is briefly discussed.

PMID- 19868736
TI  - STUDIES ON THE TOTAL BILE : II. THE RELATION OF CARBOHYDRATES TO THE OUTPUT OF
      BILE PIGMENT.
AB  - Carbohydrate feeding or injection produces often a temporary increase in the rate
      at which bilirubin is put forth in the bile, but none in the amount of the
      pigment secreted from day to day. There would appear to be no ground for the
      supposition that bilirubin is normally derived in part from the carbohydrates of
      the food.

PMID- 19868737
TI  - THE DISTRIBUTION OF RICKETTSIA IN THE TISSUES OF INSECTS AND ARACHNIDS.
AB  - In the absence of a satisfactory definition of Rickettsia the observations herein
      recorded were arbitrarily limited to bacterium-like organisms which are
      intracellular and Gram-negative. Rickettsia of this type were found in the
      following species: Amblyomma americana, Amblyomma hebraeum, Boophilus
      decoloratus, Atomus sp., Casinaria infesta, Chrysopa oculata, Ctenocephalus
      canis, Dermacentor variabilis, Lepisma saccharina, Lucoppia curviseta, Margaropus
      annulatus, Margaropus annulatus australis, Ornithodoros turicata, Pulex irritans,
      Rhipicephalus sanguineus, Rhipicephalus evertsi, and Salticus scenicus. Since
      intracellular, Gram-negative Rickettsia have been recorded in the literature as
      existing in Cimex lectularius, Dermacentor venustus, Melophagus ovinus, and
      Pediculus humanus, the occasional occurrence of such bodies must be conceded in
      the following groups not closely related phylogenetically: Attidae, Trombidiidae,
      Argasidae, lxodidae, Cinura, Acanthiidae, Pediculidae, Hippoboscidae,
      Chrysopidae, Pulicidae, and Ichneumonidae. The species which harbor Rickettsia
      differ widely in diet and habitat. One such species is insectivorous throughout
      life, two are insectivorous in larval stages, becoming vegetarian in the adult
      condition, one is chiefly vegetarian but partakes of some animal products, and
      two are usually entirely vegetarian; while the remainder subsist wholly upon a
      diet of mammalian blood. Rickettsia are associated, in only a few cases, with
      diseases in mammals. The evidence at hand does not lead beyond the conclusion
      that the Rickettsia mentioned above are true Gram-negative microorganisms, easily
      distinguishable from mitochondria and all other cytoplasmic and nuclear
      granulations, rather completely adapted to an intracellular existence, exhibiting
      in some cases a remarkable degree of host specificity, and often inherited
      through the eggs.

PMID- 19868738
TI  - THE DETERMINATION OF LUNG VOLUME WITHOUT FORCED BREATHING.
AB  - 1. A method is described for the determination of lung volumes without forced
      breathing. 2. The method determined total capacity and its subdivisions
      coincidently. 3. The values obtained were independent of the length of time
      during which the subject rebreathed after gas mixture was once established. 4.
      The maximum error of the method is estimated at +/- 3 per cent of the lung volume
      determined. Considerably greater variation from the mean may be encountered,
      however, because of inconstancy in the lung positions assumed by the subject.

PMID- 19868739
TI  - EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS :
      XII. THE EFFECTS OF SUBCUTANEOUS INJECTIONS OF VACCINES OF BACTERIUM PNEUMOSINTES
      IN MAN.
AB  - Thirteen volunteers were injected subcutaneously with a vaccine prepared from two
      strains of Bacterium pneumosintes. Three doses were given corresponding, by
      opacity tests, to 1,000, 2,000, and 2,000 million staphylococci. The intervals
      between the several injections were 5 and 8 days. Local reactions of mild and
      transitory character only were noted. Constitutional reactions, also mild and
      transitory, consisting of headache, depression, and generalized muscular pains,
      were infrequently observed. None of the men was prevented by the vaccine from
      pursuing his ordinary duties. The vaccinations induce a transitory leucocytosis
      and lead to the appearance of specific agglutinins in the blood serum.

PMID- 19868740
TI  - STUDIES ON THE RELATION OF TETANUS BACILLI IN THE DIGESTIVE TRACT TO TETANUS
      ANTITOXIN IN THE BLOOD.
AB  - 1. The sera of twenty-six individuals who carried tetanus bacilli in their
      digestive tracts all contained appreciable amounts of antitoxin. 2. The sera of
      thirty individuals in whose stools no tetanus-like organisms were found were,
      with two exceptions, free from tetanus antitoxin. 3. Although we have been unable
      to measure accurately the antitoxin content of these human carriers of tetanus
      bacilli, 0.1 cc. of serum neutralizes 10 or more M.L.D. of toxin and it is
      evident that they have acquired an active immunity due to the bacilli in the
      intestinal tract. 4. These results definitely prove that tetanus bacilli grow in
      the intestinal tract of man. 5. Many of the individuals who have no tetanus
      bacilli in their intestinal tracts and whose serum is free from antitoxin show
      agglutinins to tetanus bacilli. It is probable that they have been carriers of
      the bacilli in the past and that the agglutinins have persisted longer than the
      antitoxins. It seems likely, therefore, that these individuals are potentially
      immune to tetanus. 6. If tetanus bacilli can be established in the digestive
      tract of man we have a means of immunization which might be useful in armies or
      in regions where tetanus infections are common, though we do not recommend this
      method of immunization at present.

PMID- 19868741
TI  - THE RELATION OF ANTIBODY TO THE RATE OF DISAPPEARANCE OF CIRCULATING ANTIGEN.
AB  - 1. In rabbits previously immunized to horse serum the rate of disappearance of
      horse serum after reinjection is somewhat more rapid than in control animals not
      previously immunized. But when the average duration of the persistence of antigen
      in ten previously immunized rabbits is compared with the average duration of
      persistence in ten normal controls, the difference is not impressive. This holds
      true for animals previously immunized by repeated injections but having no free
      circulating antibody, as well as for animals having a high titer of antibody at
      the time of reinjection. The same animal may dispose of circulating antigen as
      rapidly at a time when the blood contains no precipitin as when there is a high
      titer of circulating precipitin. 2. The intravenous injection of large amounts of
      potent antihorse rabbit serum immediately after an injection of horse serum does
      not materially accelerate the rate of disappearance of the horse serum from the
      circulation. While the number of days that circulating antigen was demonstrable
      in two experiments of this type was less than the average of controls the
      duration of persistence was within the limits of variation of normal controls. 3.
      Under the condition of the experiments intravascular union of antigen and
      antibody is an unimportant factor in the mechanism for disposal of antigen. By
      exclusion it therefore seems probable that the rate of disappearance of antigen
      is largely dependent upon cell avidity for the antigen. 4. Rabbits show a wide
      range of individual variation in the rapidity with which foreign serum is
      appropriated by the tissue cells, and in their ability to form precipitins. There
      does not appear to be any close relation between the amount of precipitin set
      free in the circulation and the rate of disappearance of precipitinogen. 5. The
      type of interrelation between precipitin and precipitinogen-demonstrable not
      infrequently in patients with serum disease-in which the precipitinogen
      diminishes rapidly when the precipitin rises to the crest of its curve is
      sometimes reproduced in rabbits. The type of curve which has been observed in
      patients with little or no serum disease in which the precipitinogen persists
      steadily in the circulation for many weeks and little or no antibody is formed,
      has not been observed in the present series of rabbits.

PMID- 19868742
TI  - EXPERIMENTAL STUDIES ON INFLAMMATION : II. EXPERIMENTAL CHEMICAL INFLAMMATION IN
      VIVO.
AB  - 1. None of the salts tested produce a marked inflammation in vivo in
      concentrations under 10 per cent. Potassium salts and the different citrates
      produced atypical inflammatory reactions in mice, but not in frogs. There was no
      true inflammation, however, characterized by blood vessel changes, migration of
      polymorphonuclear leucocytes and erythrocytes, and fluid exudation. 2.
      Synergistic action occurs when equal parts of strontium and magnesium salts are
      employed. There is a change in the appearance of the mesentery without a true
      inflammation, and this change does not occur with either salt alone. 3. Amino
      acids and amines as a class do not produce inflammation, but histamine produces a
      marked inflammatory reaction in frogs and mice. 4. Tyramine does not cause an
      inflammatory reaction but has other marked effects; agglutination thrombi occur
      within the smaller blood vessels, both veins and arteries; in frogs there is a
      rapid clumping of the white blood cells followed by a true coagulation with
      strands of fibrin and entanglement of erythrocytes. This is very widespread and
      often kills the animal within an hour after injection. In mice it is the
      erythrocytes that clump and coagulation occurs very much later, usually at the
      end of 24 hours; still later there is complete absorption of the coagulated
      masses and the mesenteric circulation returns to normal. None of the mice died
      during the stage of clumping, and the clots never extended up the larger vessels
      as they did in the frogs. These effects are similar to the phenomena observed in
      the in vitro work, in which clumping of the cells appeared constantly. 5.
      Cantharidinum, histamine, and turpentine produced the most rapid and marked
      inflammation of any substances tried. These substances are all strongly
      positively chemotactic in vitro. The differences occurring when these substances
      are used in different species is a quantitative rather than a qualitative one,
      the body temperature being of some importance. Papain acted only in warmblooded
      animals; this is consistent with its chemotactic action in vitro. The degree of
      positive chemotaxis varied markedly with the blood employed and in the in vivo
      work the inflammation varied with the species of animal used. 6. Certain
      substances produced inflammation only some time after injection; this is true of
      scarlet R and croton oil in weak dilutions. These are not strongly positively
      chemotactic. 7. Parazol produces an inflammation associated with necrosis of the
      tissues. This is similar to the results obtained in vitro, parazol being
      positively chemotactic in low concentrations and negative in high concentrations.
      8. The exact chemical nature of many of the substances which produce marked
      inflammation is unknown. This is true of cantharidin, and the active constituents
      of turpentine and croton oil. 9. All substances which produce marked and rapid
      inflammation on injection are positively chemotactic, but not all strongly
      positively chemotactic substances produce inflammation; i.e., calcium compounds,
      sodium phosphate, etc. 10. Only substances which are positively chemotactic and
      also soluble in oil seem capable of producing inflammation in animals.

PMID- 19868743
TI  - EXPERIMENTAL OBSERVATIONS ON THE PROPHYLAXIS AND TREATMENT OF SYPHILIS.
AB  - 1. By inoculating the scarified surface of both sides of the scrotum of rabbits
      with suspensions of Treponema pallidum, 100 per cent of infections were obtained
      on one side or the other. Infection through the unbroken skin could not be
      produced. 2. By gland transfers from animals with positive local inoculations,
      87.5 per cent of takes were produced. 3. These two methods were used to test the
      prophylactic value of 30 per cent calomel ointment, (a) Calomel ointment proved
      efficacious up to 8 hours after inoculation with syphilis, (b) No marked
      difference appeared between the action of calomel in a base of lanolin and
      vaseline and in a base of benzoinated lard and wax. (c) Death from mercurial
      poisoning was produced in rabbits by a single application of a large amount of
      calomel ointment. 4. The method of gland transfers was used to test the
      sterilizing effect of arsphenamine and neoarsphenamine on old infections in the
      rabbit. The infection was completely abolished in every instance, whether by one,
      two, or four intravenous doses. 5. Natural spirochetosis of rabbits need not be a
      serious complicating factor in work on syphilis in rabbits, for the following
      reasons. (a) In natural spirochetosis, the lesions occur on the penis and not on
      the scrotum. Gland transfers are negative, (b) A scrotal lesion can be produced
      by inoculation, but it can be distinguished from that of Treponema pallidum
      infection by its course, (c) In studies of generalized syphilis supposed to
      involve the genitalia, and in sexual transmission experiments, Treponema cuniculi
      may be a serious complicating factor.

PMID- 19868744
TI  - THE MECHANISM OF BACTERIOSTASIS.
AB  - 1. Between Gram-positive and Gram-negative organisms gentian violet exhibits the
      same type of selective activity whether the dye be added to the media on which
      the bacteria are planted unstained (extrinsic bacteriostasis), or the organisms
      be stained with it before being planted on plain agar (intrinsic bacteriostasis).
      In both instances the Gram-positives are inhibited and the Gram-negatives
      unaffected. 2. Between Gram-positive spore-bearing aerobes and the commoner Gram
      negative bacteria, acid fuchsin, related sulfonic substances, and the flavines
      exhibit one type of selective activity when the dye is added to the media
      (extrinsic bacteriostasis) and the opposite type when it is added directly to the
      bacteria (intrinsic bacteriostasis). In the former case, the Gram-positive spore
      bearers are inhibited and the Gram-negatives unaffected; in the latter case the
      Gram-negatives are inhibited and the Gram-positive spore bearers unaffected. 3.
      Selective bacteriostasis is not necessarily conditioned by selective
      penetrability. Stained organism may grow, and dyes which do not stain well may
      inhibit reproduction. 4. There is evidence that the phenomena of bacteriostasis
      may be due to changes effected by the dye at the surface of the organisms.

PMID- 19868745
TI  - INFLUENCE OF SODIUM SALICYLATE UPON THE ARTHRITIS OF RABBITS INOCULATED WITH NON
      HEMOLYTIC STREPTOCOCCI.
AB  - 1. Rabbits inoculated intravenously with non-hemolytic streptococci, while under
      the influence of full therapeutic doses of sodium salicylate, developed almost as
      many inflamed joints as the untreated controls similarly inoculated. 2. The
      salicylated rabbits, on the other hand, had a much higher proportion of mildly
      inflamed Joints than did the controls. 3. This anti-inflammatory action was most
      evident in the animals inoculated with streptococci of the lowest virulence, and
      could not be demonstrated in animals inoculated with hemolytic streptococci.

PMID- 19868746
TI  - THE INFLUENCE OF CALCIUM CHLORIDE UPON EXPERIMENTAL BOTULISM.
AB  - 1. Calcium chloride given subcutaneously, intraperitoneally, or intravenously has
      been found to have no effect upon the production of botulism following the
      injection of Bacillus botulinus (Strain 80B) into the peritoneal cavity of guinea
      pigs. 2. Treatment of Bacillus botulinus with alcohol has been found markedly to
      decrease its toxicity for guinea pigs. This is in conformity with the work of
      Bronfenbrenner and Schlesinger. 3. Toxin-free spores of Bacillus botulinus have
      been found pathogenic for guinea pigs. 4. No prejudice as to possible results in
      rabbits should be based upon the above conclusions.

PMID- 19868747
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : I. THE SPONTANEOUS TUMOR AND
      ASSOCIATED ABNORMALITIES.
AB  - A malignant tumor which developed at the site of a primary syphilitic lesion in
      the scrotum of a rabbit, about 4 years after inoculation, and eventually led to
      the death of the animal, has formed the basis for an extensive series of
      investigations beginning with the study of the spontaneous tumor. The present
      report contains the clinical history of the animal from the time of inoculation
      to its death and the results of pathological examinations. The most important
      events recorded may be summarized as follows: 1. A mild but persistent syphilitic
      infection with an occasional relapse and the eventual development of chronic
      inflammatory lesions in the skin associated with atypical epithelial
      proliferations. 2. The occurrence, at about the same time, of extensive
      degenerative changes in the dermis accompanied by an atypical growth of hair
      follicles, with the production of diffuse and nodular areas of thickening and
      induration (scleroderma). 3. The development of a growth in the skin of the left
      scrotum which recurred after removal and spread diffusely over adjacent parts of
      the skin, and metastasized to the regional lymph nodes and to internal organs. 4.
      The transplantation of the growth to other rabbits by intratesticular inoculation
      and the successful propagation of the growth over a period of nearly 2 years
      (twenty generations). 5. The development of a cachexia and of pressure phenomena
      from metastases involving the cervical and lumbar regions of the spinal column
      which eventually led to the death of the animal. 6. The discovery, post mortem,
      of an extensive leucoplakia of the tongue and buccal mucosa, chronic inflammatory
      lesions in the esophagus with atypical epithelial proliferation, and a nodular
      growth in the left testicle differing in character from that in the scrotum. 7.
      The presence of extensive degenerative changes in the vascular system,
      degeneration of the parenchymatous organs, atrophy of the thymus and lymphoid
      system, with chronic lymphadenitis, atrophy, degeneration, and necrosis of the
      suprarenals, and atrophy and hyperplasia of the thyroid with chronic thyroiditis.
      The conclusion was reached that the growth in the scrotum represented a neoplasm
      of epithelial origin which was composed of cells allied to those found in the
      bulb and root sheath of the hair. No explanation was offered for the origin or
      unusual malignancy displayed by the tumor pending the introduction of
      experimental data. It was stated, however, that the evidence presented was
      sufficient to warrant the assumption that the factor of foremost importance in
      the development of the tumor was constitutional rather than local.

PMID- 19868748
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : II. PRIMARY TRANSPLANTATION
      AND ELIMINATION OF A COEXISTING SYPHILITIC INFECTION.
AB  - Several attempts were made to transplant a spontaneous malignant tumor in a
      syphilitic rabbit before a method was devised which proved successful.
      Subcutaneous and intracutaneous inoculations were unsuccessful on account of the
      vigorous granulomatous reaction which was aroused by the introduction of tumor
      fragments into these tissues. This difficulty was overcome by the use of
      intratesticular inoculations. With this method, a good growth was obtained in
      practically all animals. It appeared possible, however, that a syphilitic
      infection had been transmitted along with the tumor, and hence treatment with
      arsphenamine was instituted as a means of eliminating this infection. A study of
      the transplanted tumor in the first and second generations showed that it
      possessed a high degree of malignancy. Metastases occurred at an early period in
      the majority of animals, and while some of them appeared to recover, the
      indications were that more than 50 per cent might be expected to succumb to the
      effects of the tumor growth within a period of 6 to 7 months. The method of
      intratesticular inoculation now in use is described in detail.

PMID- 19868749
TI  - STABLE SUSPENSIONS OF AUTOAGGLUTINABLE BACTERIA.
AB  - Autoagglutinating cultures of Type G, bacillus of rabbit septicemia, can be
      rendered stable by suspension in glycocoll-acetate-phosphate buffer mixtures pH
      7.5 and 7.1. Distilled water suspensions can also be employed if the normal and
      immune serum under test is diluted with buffers of this pH instead of with 0.85
      per cent NaCl. Five intensely autoagglutinable strains of Streptococcus
      haemolyticus have been stabilized by washing and by suspending in 0.001 N NaOH.
      Specific agglutination of these stable suspensions by rabbit antistreptococcus
      serum could be demonstrated by diluting the serum with M/320 NaCl.

PMID- 19868750
TI  - ANTAGONISTIC GROWTH-ACTIVATING AND GROWTH-INHIBITING PRINCIPLES IN SERUM.
AB  - The substances precipitated by CO(2) from the serum of chickens 1 or 2 years old
      slightly increased the activity of pure cultures of a 10 year old strain of
      fibroblasts, an indication that a growth-promoting substance had been obtained
      from the serum. The rate of growth of fibroblasts was slower in serum deprived of
      its globulins and the increase of the inhibiting effect of the treated serum is
      thus manifested. It would appear that the inhibiting action of serum is referable
      to one or several growth-activating substances which precipitate by CO(2), and to
      one or several growth-retarding substances which remain in the supernatant serum
      after the precipitate has been thrown down by centrifugation. It may be concluded
      that, under the conditions of the experiments: 1. A substance enhancing the
      proliferative activity of homologous fibroblasts is precipitated from serum by
      CO(2). 2. The serum from which the precipitate has been removed inhibits the
      proliferation of homologous fibroblasts more markedly than does the original
      serum. The solution of the precipitate in the treated serum has about the same
      effect on fibroblasts as the original serum. 3. The restraining effect of serum
      on the activity of homologous fibroblasts is due in part to the antagonistic
      action of growth-activating and inhibiting substances.

PMID- 19868751
TI  - SURFACE TENSION OF SERUM : V. RELATION BETWEEN TIME-DROP AND SERUM ANTIBODIES.
AB  - An attempt was made to apply to the study of immune sera the fact, pointed out in
      our previous papers, that at a given dilution the serum shows a maximum drop of
      surface tension in function of time (time-drop). The results of the experiments
      here reported would seem to indicate that: 1. The time-drop of a serum solution
      is greater after the animal has been immunized than before immunization (from 50
      to 100 per cent). 2. The time-drop is maximum at a dilution of 1:10,000, as had
      been predicted from the data previously acquired. 3. The size of the molecules or
      micellae is probably unchanged after immunization, since the maximum drop is not
      shifted then. 4. Measurements made during the process of immunization showed that
      the time-drop increases after the 8th day and second injection, and reaches a
      maximum toward the 13th day, while the controls undergo no increase. 5. The
      injection of substances non-productive of antibodies, such as homologous cells or
      turpentine, does not result in the production of a permanent maximum. This shows
      that the maximum observed when heterologous cells are used is due to the presence
      of antibodies, and not to the mere injection of foreign material. 6. The
      measurement of the refractive index of the sera failed to demonstrate any
      differences between the sera of the controls and those of the experimental
      animals.

PMID- 19868752
TI  - THE ABSORPTION OF SPECIFIC AGGLUTININS IN HOMOLOGOUS SERUM FED TO CALVES DURING
      THE EARLY HOURS OF LIFE.
AB  - The administration of cow serum by feeding may replace colostrum. The agglutinins
      towards Bacillus abortus in it are absorbed during the first hours of life in
      relatively large amounts when compared with those naturally appearing in ordinary
      milk. It seems probable that colostrum is the most efficient transporting agent
      of the antibodies. Experiments are under way to put these conclusions on a
      quantitative basis with special reference to the age of the calf during which the
      absorption of homologous antibodies is still possible.

PMID- 19868753
TI  - STUDIES ON THE TOTAL BILE : III. ON THE BILE CHANGES CAUSED BY A PRESSURE
      OBSTACLE TO SECRETION; AND ON HYDROHEPATOSIS.
AB  - In bile that is secreted against an abnormally high pressure, as during partial
      obstruction, the pigment, cholate, and cholesterol outputs are all cut down, and
      so much more than is the fluid bulk that the concentration of the substances per
      cubic centimeter of bile is notably lessened. The fluid obtained at the greatest
      pressure compatible with secretion contains traces only of the typical biliary
      constituents. The bearing of these alterations in the bile on the consequences of
      partial biliary obstruction is discussed. An analysis of the liver changes
      following biliary obstruction brings out their essential likeness to the changes
      that occur under similar circumstances in glands in general and the kidney in
      particular. The major physiological factors concerned in the development of
      hydronephrosis and in the liver changes after biliary obstruction are identical.
      We would suggest that the term hydrohepatosis as applied to the liver condition
      would be useful not merely to designate it but to indicate the principles
      underlying its development. In clinical instances of biliary obstruction, the
      likeness to hydronephrosis is often hidden because of the activity of the gall
      bladder to render the stasis bile dark and thick. There is then a concealed
      hydrohepatosis, differing merely by the character of the duct content, from the
      manifest hydrohepatosis with "white bile," that is found when the gall bladder
      fails to act.

PMID- 19868754
TI  - STUDIES ON THE TOTAL BILE : IV. THE ENTEROHEPATIC CIRCULATION OF BILE PIGMENT.
AB  - In dogs fed the green bile or the liver tissue of herbivora, the bile later
      secreted frequently becomes green, changing from the previous yellow-brown. When
      they are fed sheep bile that contains cholohematin, their bile comes to contain
      this pigment. When they are fed dog bile in quantity a well marked increase in
      the output of bilirubin by the liver frequently follows. Taken together, these
      facts indicate the existence of an enterohepatic circulation of bile pigment.

PMID- 19868755
TI  - BOTULISM. STUDIES ON THE MANNER IN WHICH THE TOXIN OF CLOSTRIDIUM BOTULINUM ACTS
      UPON THE BODY : I. THE EFFECT UPON THE AUTONOMIC NERVOUS SYSTEM.
AB  - A survey of the results of these experiments shows, we believe conclusively, that
      in botulinus intoxication in cats, dogs, and rabbits there is a specific effect
      upon the portions of the autonomic nervous system which Gaskell (14) described as
      the bulbosacral and prosomatic outflows of connector fibers respectively, which
      results in a blocking of the nerve impulses of these nerves. The experimental as
      well as the clinical evidence indicates that there is no damage to the nerves of
      the thoracicolumbar outflow. The exact location of the damage has not been
      ascertained nor has the mechanism by which the nerve impulse is blocked been
      determined. The experiments show, however, that the lesions in these portions of
      the nervous system are not of central distribution but are peripheral, and that
      the block cannot be due to an organic break in the conduction apparatus but must
      be due to some derangement which is relatively unstable. If it were otherwise it
      would not be possible to induce a physiological response even by massive
      stimulation, nor could the response be subsequently repeated by stimuli which lie
      within the limits of normal intensity. The application of the results of these
      experiments to the clinical manifestations of botulism will be discussed in a
      later report after the effect of the toxin upon the skeletal motor nerves has
      been described.

PMID- 19868756
TI  - THE RELATION BETWEEN BLOOD DESTRUCTION AND THE OUTPUT OF BILE PIGMENT.
AB  - In dogs intubated for the collection of all of the bile, a marked falling off in
      the yield of bilirubin is regularly to be noted after operation, followed soon by
      an anemia of secondary character. Though, in the absence of complications, the
      anemia is mild, it persists despite the excellent general condition of the
      animal. Intercurrent changes in the hemoglobin percentage take place from time to
      time, and these are accompanied by very similar fluctuations in the bilirubin
      quantity. At first inspection the data strongly suggest that blood destruction
      finds accurate quantitative expression in the yield of bile pigment. But this is
      not the case. True, the destruction finds expression in terms of bile pigment and
      practically at once; and the data support the conception that bilirubin has no
      other sources besides the hemoglobin of destroyed blood. But our experiments show
      that the amount of it put forth during the development of an anemia from gradual
      blood destruction, either intercurrent or induced, is far below that derivable
      from the net quantity of hemoglobin disappearing from the circulation. The
      discrepancy is referable to a process of pigment conservation which varies in
      proportion to the body need. We have shown in a previous paper that bile pigment
      may on occasion beabsorbed from the intestinal tract. This fact and those
      reported in the present communication lead one to question the accepted view that
      bilirubin is mere waste material eliminated by way of the liver. The anemia which
      develops upon total loss of the bile is not improbably consequent on the pigment
      loss therewith. Current methods of computing the rate of normal and pathological
      blood destruction from the bilirubin (or urobilin) yield are unsound in principle
      and open to large error in practise. Yet there is no doubt that day-to-day
      variations in the output of bile pigment result from changes in the blood; and on
      occasion they provide enlightening evidence of the nature of hemic events.

PMID- 19868757
TI  - ACTION OF SERUM ON FIBROBLASTS IN VITRO.
AB  - IT MAY BE CONCLUDED THAT, UNDER THE CONDITIONS OF THE EXPERIMENTS: 1. The
      duration of life of fibroblasts is not altered by the presence of 7 per cent
      serum in a medium composed of fibrin and Tyrode solution, but is slightly
      decreased when the concentration of the serum reaches 25 per cent. 2. Fibroblasts
      cultivated in serum or in Tyrode solution are only in a condition of survival;
      they do not build up new protoplasm from the serum proteins and their mass does
      not increase. 3. When embryonic tissue juice is added to the medium, the tissues
      increase in mass. But the rate of growth is the same in media containing 0 per
      cent and 10 per cent serum. In 25 per cent serum, however, the rate of growth
      slightly decreases. Even in the presence of embryonic tissue juice, serum does
      not increase the rate of growth of connective tissue. 4. The nitrogenous
      compounds contained in serum are not used as food material by fibroblasts growing
      in vitro.

PMID- 19868758
TI  - SEPARATION OF THE TOXINS OF BACILLUS DYSENTERIAE SHIGA.
AB  - By the suppression, through anaerobiosis, of the exotoxin-producing activity of
      Bacillus dysenteriae Shiga a pure endotoxin is produced directly from the
      culture. The duality of the poison of Shiga bacillus is further substantiated by
      studies on the diffusion of exotoxin, or neurotoxin, and endotoxin, or
      enterotoxin, by means of collodion sacs, implanted intraabdominally in rabbits or
      placed in vitro.

PMID- 19868759
TI  - THE VIRULENCE OF AN EPIDEMIC STRAIN OF BACILLUS PESTIS CAVIAE.
AB  - Ever since Pasteur's demonstration of the modifying effect of animal passage on
      the virulence of bacteria, this device has been regarded as of great importance
      in intensifying infective capacity. It is not often, however, that extensive
      parallel tests have been made of the power of a microorganism to produce
      infection in a species of animal which is its natural habitat and under
      conditions in which the normal as well as artificial portal of entry is employed,
      and the potency of the microorganism passed directly from host to host is closely
      contrasted with that of one merely artificially cultivated outside the body. The
      experiments described in this paper were arranged to fulfill these conditions.
      The results show that with the particular strain of Bacillus festis caviae used,
      successive animal passages do not modify infective capacity, or virulence. This
      finding is in harmony with the observations previously made from which it was
      concluded that the epidemic curve of mouse typhoid infection is explicable solely
      on the basis of bacillary distribution and host susceptibility.

PMID- 19868760
TI  - THE PRODUCTION OF ANTIBODIES IN RABBITS BY A SIMPLIFIED INTRATRACHEAL METHOD.
AB  - The method described of producing antibodies by the administration of antigens
      through the larynx is simple. The results obtained, however, conform closely to
      those obtained through intraperitoneal injection. The procedure is relatively a
      safe one and may well be employed in experimental inoculations. The advantages of
      rapidity and painlessness are obvious. In addition, gross injury has not been
      observed. Injections may be repeated at frequent intervals without danger to the
      life of the animal. The tube illustrated in Text-fig. 1 extends a little over 1
      cm. into the trachea. The tube designed for the guinea pig reaches 2 or 3 mm.
      below the glottis. While the doses indicated in the protocols are small, 7 to 10
      cc. of liquid have been given to rabbits by means of the tube without ill
      effects. It has been shown by the injection of India ink that the material is
      well distributed throughout the lungs in both the rabbit and guinea pig. Under
      certain conditions it may be advisable to inject more deeply into the trachea,
      especially in the rabbit. The tube illustrated in Text-fig. 1 is not adaptable
      for this purpose. A cannula of larger diameter has proved of distinct advantage
      as a shield for introducing flexible catheters well down the trachea. A cannula 9
      cm. long and 4 mm. in diameter when bent at an angle of 45 degrees may be passed
      through the larynx of a rabbit without difficulty. A No. 8 (French) woven or No.
      10 soft rubber catheter may be inserted into the cannula beyond the bend before
      the tube is passed through the glottis. After the tube has entered the glottis
      the catheter then may be introduced as deeply as desired into the teachea. The
      metal cannula enables the operator to "feel" the glottis. From the experiments
      one seems justified in concluding that the results obtained by administering
      antigens by way of the trachea are about the same as those obtained by the
      intraperitoneal route. With the tubes described injury has been largely
      eliminated. The procedure is relatively a safe one.

PMID- 19868761
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : III. INTRATESTICULAR
      TRANSPLANTATION AND CLINICAL COURSE OF THE DISEASE.
AB  - The results obtained by intratesticular inoculation of a malignant tumor of the
      rabbit are presented in the form of a general summary covering the phenomena of
      growth and spontaneous regression of the tumor and the clinical evidence of
      disease in tumor animals. Under ordinary circumstances, growth is obtained by
      this method of inoculation in practically all animals, and the majority of them
      show metastases. The ultimate fate of tumor animals is variable. Spontaneous
      regression is of frequent occurrence, and apparent recovery may take place even
      after extensive metastases have developed. More often, the disease terminates
      fatally. The course of the disease may be fulminating in character with death
      occurring 6 to 7 weeks after inoculation, or it may be prolonged over a period of
      more than 6 months, but death usually occurs between 7 weeks and 3 months after
      inoculation. The symptomatology varies with the course of tumor growth but is in
      general that of a debilitating disease of an acute or chronic character in which
      the picture is frequently complicated by symptoms referable to mechanical causes
      or to one or more of the glands of internal secretion. The most prominent of
      these are due to the presence of metastases in the suprarenals or pituitary body,
      in which case symptoms of Addison's disease or diseases of the pituitary may be
      superimposed upon those attributable to the presence of extensive tumor growths.
      In the absence of such growths, however, the symptoms of suprarenal or pituitary
      involvement may dominate the picture.

PMID- 19868762
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : IV. THE RESULTS OF
      MISCELLANEOUS METHODS OF TRANSPLANTATION, WITH A DISCUSSION OF FACTORS
      INFLUENCING TRANSPLANTATION IN GENERAL.
AB  - The results of seven methods of transplantation of a malignant tumor of the
      rabbit are reported and contrasted with results obtained by intratesticular
      inoculation. It was found that inoculations made into the brain, the anterior
      chamber of the eye, and the muscles gave an almost uniform series of takes with
      the production of comparatively large and vigorously growing tumors.
      Intracutaneous inoculations were less favorable, while with subcutaneous,
      intravenous, and intraperitoneal inoculations, a growth was obtained in only 20
      to 25 per cent of the animals. In contrast with the malignant course of the
      disease produced by testicular transplantation, the tumors produced by methods
      other than intracerebral inoculation were relatively benign. In all cases, the
      growth was of a purely local character; in some instances, there was invasion of
      the surrounding tissues with local or regional extension of the growth, but no
      metastases developed in distant organs. Tumors in the brain soon caused death as
      a result of pressure, and the ultimate fate of tumors in the eye was not
      determined, but the growth produced by other methods of local inoculation was of
      relatively short duration and terminated with spontaneous resolution. It was
      found that while a good growth could be obtained with material which had been
      subjected to repeated freezing, thawing, and grinding, the use of cell-free
      filtrates or desiccated tumor tissue gave negative results. In discussing the
      experiments reported, it was pointed out that there were three groups of factors
      which had played important parts in determining the results of transplantation.
      These were the capacity for growth of the tumor cells, animal resistance, and the
      advantage given the tumor or the animal by the use of a particular method of
      inoculation. From an analysis of the results obtained with reference to the
      operation of these factors, the conclusion was reached that while the quality of
      malignancy displayed by the tumor was conditioned upon the capacity for growth of
      the tumor cells, the degree of malignancy exhibited in any given instance was a
      function of animal resistance which was not entirely specific but corresponded
      closely with the ability of the animal to meet excess demands arising from other
      causes and, to this extent, represented an expression of the functional capacity
      of a mechanism which is concerned primarily with the maintenance of the general
      animal economy.

PMID- 19868763
TI  - THE DEPOSITION AND SUBSEQUENT COURSE OF PARTICULATE MATERIAL (MANGANESE DIOXIDE
      AND MANGANESE META-SILICATE) ADMINISTERED INTRAVENOUSLY TO CATS AND TO RABBITS.
AB  - 1. Suspensions of manganese dioxide given intravenously to the cat are virtually
      eliminated from the body in 1 week (168 hours). 2. As this process of removal
      goes on, there is a transfer of manganese from lungs to liver. 3. Similar
      suspensions of manganese dioxide given intravenously to rabbits are excreted more
      rapidly, owing to the fact that in these animals the lungs are not involved and
      the whole process of removal from the blood is carried on by the liver. 4. A
      method for the quantitation of rhodonite (manganese metasilicate) is given. 5.
      Three different suspensions of rhodonite, varying in the size of the largest
      particles from 1.3 to 0.2micro, when injected intravenously into cats show a
      greater and greater tendency toward arrest in the liver as the size of the
      individual particles becomes smaller. 6. When rhodonite suspensions containing
      particles averaging 1.1micro in diameter are injected intravenously into cats,
      the primary sites of deposition are similar to those observed for manganese
      dioxide suspensions similarly injected. The disappearance of rhodonite is
      exceedingly slow and is apparently completed in about 50 days following
      injection. 7. Rhodonite should prove a suitable substance with which to attempt
      the production of lung fibrosis in cats through the medium of intravenous
      injection. Manganese dioxide, while a useful agent for studying the immediate
      sites of localization of particulate material carried by the blood, lacks
      permanency after deposition and is consequently unsuitable for studies upon
      chronic changes induced by foreign substances.

PMID- 19868764
TI  - ARSENICAL COMPOUNDS IN THE TREATMENT OF BLACKHEAD IN TURKEYS.
AB  - The natural form of blackhead, although very fatal to young turkeys, is favorably
      influenced by treatment with certain of the newer arsenical compounds.
      Neoarsphenamine injected intravenously in toxic doses has a somewhat favorable
      effect on the course of the spontaneous disease and evidently lowers the
      mortality. Its instability, its pronounced toxicity for young turkeys, as well as
      the difficulty of obtaining amounts suitable for the cases to be treated on any
      one occasion, serve to make its employment impracticable. Less favorable results
      were obtained with atoxyl. Arsenious acid fed daily in small doses failed to
      prevent blackhead and possibly increased the incidence of infection. In larger
      doses it failed to cure spontaneous blackhead. Tryparsamide may be injected in
      cases of spontaneous blackhead in doses as high as 1 gm. per kilo of body weight
      either intravenously or subcutaneously without serious toxic effect. Prompt
      clinical improvement usually follows and the mortality is undoubtedly greatly
      lowered. With inoculated blackhead recovery is more difficult to obtain. Birds
      treated by injections of either neoarsphenamine or atoxyl failed to recover.
      There were two recoveries among three tryparsamidetreated cases. An attempt to
      cure inoculated blackhead at an advanced stage by the injection of tryparsamide
      failed. The study of the lesions of treated turkeys shows that tryparsamide, and
      to some extent neoarsphenamine, have a more pronounced effect on the liver
      lesions than on the disease in the lung, which accounts for the discrepancy in
      the results of the treatment of spontaneous and inoculated blackhead. There is
      histological evidence of prompt absorption of necrotic liver parenchyma;
      moreover, the protozoa are destroyed more rapidly in the liver than in the lung.
      Tryparsamide has the most pronounced curative action on blackhead infection of
      any of the drugs thus far tested. Either intravenous or subcutaneous injection of
      appropriate doses of this drug at the first appearance of symptoms should serve
      to cure the majority of cases of blackhead.

PMID- 19868765
TI  - BACTERIOSTASIS BY MIXTURE OF DYES.
AB  - It is possible to mix two dyes of opposite selective bacteriostatic powers and
      obtain a mixture which combines the powers of the two components. This
      possibility has been established by experiments with a mixture of gentian violet,
      which has a predilection for Gram-positive organisms, and acriflavine, which has
      a predilection for Gram-negatives; a mixture of these two dyes is quite
      bactericidal for both groups of bacteria. The weakness of each dye, when used
      alone, is thus, in the mixture, fortified by the strength of the other.

PMID- 19868766
TI  - THE INFLUENCE OF THE SUPRARENAL CORTEX ON THE GONADS OF RABBITS : II. THE EFFECTS
      OF SUPRARENAL INJURY (BY REMOVAL OR FREEZING) ON THE TUBULES AND INTERSTITIAL
      CELLS (LEYDIG) OF THE TESTIS.
AB  - 1. Double or partial suprarenalectomy in rabbits produces no specific changes
      either in the tubules or in the interstitial cells of the testes. 2. This is in
      sharp contrast with the marked hypertrophy of the interstitial cells of the ovary
      which usually occurs in rabbits surviving double suprarenalectomy 30 days or
      more. 3. These facts indicate that the interstitial cells of the testis and ovary
      are not functionally homologous.

PMID- 19868767
TI  - PATHOGENESIS OF THE OCULAR LESIONS PRODUCED BY A DEFICIENCY OF VITAMINE A.
AB  - The earliest lesions in ophthalmia of rats resulting from a deficiency of
      vitamine A consist in focal inflammatory lesions in the conjunctivae of the lids
      and nictitating membrane. The involvement of the cornea, which constitutes the
      most conspicuous feature of the well developed ophthalmia, is a secondary
      phenomenon. The characteristic corneal plaque consists of keratinized epithelium
      beneath which the deeper layers of epithelium are generally found intact.
      Pathologically, the ocular manifestations of a deficiency of vitamine A are
      referable to a low grade inflammatory process, originating in the palpebral
      conjunctiva and spreading to the cornea. The rapidity of development and the
      degree of destruction probably depend in large part on the type of bacterial
      infection. The specific changes which lead to the establishment of such an
      infection have not been determined. It is conceivable that they may be either
      physiological or anatomical. There is some evidence in favor of a general
      disturbance of antibody formation in animals on deficient diets. The possibility
      of a disturbed function in the paraocular glands must be considered.

PMID- 19868768
TI  - CHANGES IN THE PARAOCULAR GLANDS ACCOMPANYING THE OCULAR LESIONS WHICH RESULT
      FROM A DEFICIENCY OF VITAMINE A.
AB  - There is evidence suggesting that the ophthalmia which results from a deficiency
      of vitamine A is secondary to some change outside the eyes, and that this change
      may lie in the paraocular glands. In rats these glands consist of the lacrimal,
      with its watery secretion, the Harderian, with a probable fatty product, and the
      Meibomian glands. A histological study of these structures shows questionable
      changes in the lacrimal and Meibomian glands, and marked changes in the Harderian
      gland. The changes in the Harderian gland are both degenerative and inflammatory.
      The degenerative changes consist of swelling, vacuolation, and occasionally
      complete epithelial disintegration. The inflammatory lesions may be either acute
      or chronic. The acute reactions are sometimes diffuse, but are more often focal.
      Definite suppuration occasionally results. The acute process generally passes
      over into a chronic inflammation with mononuclear cell infiltration, fibrosis,
      and atrophy. The changes demonstrated indicate a serious disturbance in the
      secretion of the Harderian gland, such as may conceivably render the conjunctiva
      susceptible to infection. Theses studies suggest the importance of investigating
      the paraocular glands in other types of conjunctival infection. It is possible
      that they may have a definite relation to the origin and course of such
      infections.

PMID- 19868769
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE. I.

PMID- 19868770
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE. II.
AB  - 1. Six strains of paratyphoid-enteritidis bacilli, isolated from man and animals,
      differed markedly in virulence for mice. 2. The inherent virulence of each strain
      for mice was not affected by repeated intraperitoneal and per os mouse passage.
      3. Individual differences in the susceptibility of the mice to each strain and to
      graded doses of mercury bichloride were demonstrable. Such variations appear to
      be of a non-specific nature.

PMID- 19868771
TI  - THE EFFECT OF SODIUM CHLORIDE ON THE CHEMICAL CHANGES IN THE BLOOD OF THE DOG
      AFTER PYLORIC AND INTESTINAL OBSTRUCTION.
AB  - Experiments to determine the effect of furnishing an ample supply of sodium
      chloride on the toxemia of pyloric and intestinal obstruction are reported. A
      fall in chlorides is the first and seemingly most significant change to take
      place in the blood after pyloric and intestinal obstruction. The chloride is
      apparently utilized by the body as a protective measure against the primary toxic
      substance. Two dogs with pyloric obstruction were given 50 cc. of 10 per cent
      NaCl subcutaneously daily. One lived 3 days, the other 4. The blood showed little
      change, except a marked terminal rise in chlorides. Animals given a like amount
      of distilled water or 25 per cent glucose showed the changes typical of untreated
      animals. The obstruction of the pylorus was released in six dogs 48 to 72 hours
      after the initial operation. Two died within 24 hours after the second operation
      with a high non-protein nitrogen in the blood. Two survived but showed a high
      level of non-protein nitrogen in the blood and a high nitrogen excretion in the
      urine, low blood chlorides, and a marked alkalosis. One dog in such a state died
      on the 13th day from peritonitis, arising in a wound infection. The other showed
      a marked fall in non-protein nitrogen in the blood following the administration
      of 10 gm. of sodium chloride by mouth, but died following the intravenous
      injection of 25 per cent sodium chloride. Two animals were given 50 cc. of 10 per
      cent NaCl subcutaneously, at the time of the second operation. The blood rapidly
      returned to normal and complete recovery followed. Two dogs with the duodenum
      obstructed by section and inversion of the cut ends were treated with 10 per cent
      sodium chloride after the obstruction had existed for 48 hours and the
      characteristic blood changes had developed. The non-protein nitrogen returned to
      normal within 48 hours after treatment was begun. One dog died following a
      lateral anastomosis for relief of the obstruction. A second operation was not
      attempted in the other animal. Two dogs in which the duodenum was obstructed by
      section and inversion of the cut ends were given 500 cc. of 0.85 per cent NaCl
      subcutaneously on the day of operation and each day thereafter until death. One
      dog lived 21 days, the other 28. Both dogs showed a marked alkalosis, but never
      any rise in the non-protein nitrogen of the blood. The animals at autopsy showed
      intussusception of the ileum with extensive ulceration. In one there was a
      perforation and terminal peritonitis. The operation wounds healed normally. Three
      dogs with section of the duodenum were given 500 cc. of distilled water every
      day. One died in 24 hours, one in 48 hours, and the third in 72 hours. Autopsy
      showed no cause for death other than toxemia. One dog with section of the
      duodenum was given 500 cc. of 2 per cent glucose every day. The blood showed a
      rapid rise in non-protein nitrogen and carbon dioxide-combining power, and a fall
      in chlorides. The animal died 72 hours after operation. Three dogs with section
      of the duodenum were given 500 cc. of 1 per cent sodium bicarbonate every day.
      One dog died in 72 hours, one lived 7 days, and the third lived 9 days. All
      developed a high non-protein nitrogen in the blood and two showed marked clinical
      symptoms of an alkalosis. These results demonstrate that solutions of sodium
      chloride have a marked effect in preventing and controlling the toxemia of
      pyloric and intestinal obstruction as shown in clinical symptoms and in chemical
      changes in the blood. Dogs given an abundant supply of distilled water died more
      quickly than untreated control animals. Solutions of glucose have no specific
      value, and sodium bicarbonate solutions prolong life only a short while. Good
      therapeutic results have been obtained with very concentrated sodium chloride
      solutions, and with dry sodium chloride given by mouth. It seems evident that
      sodium chloride has a specific action in preventing and possibly in controlling
      the changes produced by the toxic body. Sodium chloride is a valuable therapeutic
      agent in pyloric and high intestinal obstruction.

PMID- 19868772
TI  - THE SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS.
AB  - 1. A method is given for the concentration and purification of the soluble
      specific substance of the pneumococcus. 2. The material obtained by this method
      is shown to consist mainly of a carbohydrate which appears to be a polysaccharide
      built up of glucose molecules. 3. Whether the soluble specific substance is
      actually the polysaccharide, or occurs merely associated with it, is still
      undecided, although the evidence points in the direction of the former
      possibility.

PMID- 19868773
TI  - IMMUNOLOGICAL RELATIONSHIPS OF CELL CONSTITUENTS OF PNEUMOCOCCUS.
AB  - 1. The protein precipitated by acetic acid from solutions of pneumococci shows
      chemical reactions characteristic of nucleoprotein and mucoid. 2. The protein of
      pneumococcus, as contrasted with the non-protein soluble specific substance,
      exhibits species specificity rather than the type specificity characteristic of
      the latter.

PMID- 19868774
TI  - SURFACE TENSION OF SERUM : VI. THE STUDY OF IMMUNE SERUM. TIME-DROP AND INITIAL
      VALUE OF SURFACE TENSION.
AB  - 1. The initial surface tension of serum or serum solutions is not affected
      systematically by the presence of antibodies in the serum. On the contrary, the
      time-drop in 2 hours is always increased, from 25 to 100 per cent. 2. It is
      extremely important, in order to demonstrate these phenomena, that the greatest
      care be taken regarding the cleanness of the vessels and the purity of water and
      NaCl. 3. It is equally important to use a device, for example such as is pictured
      in this paper, capable of preventing the jarring and shaking of the liquid. 4.
      The value of the time-drop of a normal, healthy serum is never higher than 10
      dynes. Should it be higher, the serum must not be used for immunity experiments.

PMID- 19868775
TI  - MUTATION AMONG HOG-CHOLERA BACILLI.
AB  - 1. In the hog-cholera group the mutation from smooth (A) to granular (B) type
      occurs and a mutant with a moist, opaque colony formation was noted. 2. The B
      mutant when obtained pure remains a B type without reversion in the stock
      cultures. 3. The B mutant can be made to assume some of the A characters by rapid
      successive transplanting in bouillon. 4. The B mutant can usually be found in
      older transplants of A. 5. The two types may be distinguished by certain cultural
      characters, by slightly different agglutination reactions, and by different
      degrees of virulence.

PMID- 19868776
TI  - THE INFLUENCE OF THE SUPRARENAL CORTEX ON THE GONADS OF RABBITS : I. THE EFFECTS
      OF SUPRARENAL INJURY (BY REMOVAL OR FREEZING) ON THE INTERSTITIAL CELLS OF THE
      OVARY.
AB  - 1. Moderate or marked ovarian enlargement has been observed in 76 per cent of
      rabbits which survived double suprarenalectomy over 30 days. 2. The ovarian
      enlargement consists essentially of an hypertrophy of the interstitial cells. 3.
      The hypertrophy of the interstitial cells is a compensatory reaction and adds
      further data to the functional interrelation between the suprarenal cortex and
      the interstitial cells.

PMID- 19868777
TI  - THE PRESENCE OF BACTERIA IN THE LUNGS OF MICE FOLLOWING INHALATION.
AB  - 1. When mice are exposed to an atmosphere containing cultures of bacteria in the
      form of a fine mist, the bacteria readily penetrate into the lower respiratory
      tract. 2. Pneumococci which have reached the lung as a result of this procedure
      usually disappear within a few hours and give rise to no infection. Hemolytic
      streptococci, on the other hand, persist in the lung for a considerably longer
      time and a general septicemia usually follows. 3. Attempts to determine the
      conditions under which pneumococci which have reached the lung by inhalation may
      induce a local or general infection have not been successful.

PMID- 19868778
TI  - PRODUCTION OF HETEROGENETIC ANTIBODIES WITH MIXTURES OF THE BINDING PART OF THE
      ANTIGEN AND PROTEIN.
AB  - 1. The alcohol-soluble extract of heterogenetic antigen, which possesses the
      specific chemical structure of the entire antigen, has a detectable but generally
      very slight power to increase the amount of heterogenetic antibodies, when
      injected into rabbits. 2. This substance can be transformed into an efficient
      antigen by mixing it with protein solutions such as diluted normal serum. 3. Such
      mixtures are considerably more active than the same substances injected
      separately. Therefore, the effect of the serum is probably due to the formation
      in vitro of a loose compound between the alcohol-soluble substance and protein,
      the compound acting as a complete antigen. 4. It may be supposed that there
      exists a group of natural antigens which are built up of one specifically
      reacting part that is almost or entirely devoid of antigenic properties, and
      another part, a protein, responsible for the immunizing effect.

PMID- 19868779
TI  - AN INFECTIOUS OPHTHALMIA OF CATTLE.
AB  - Twenty-four cases of an acute ophthalmia of cattle have been observed. The
      infection is characterized by photophobia, severe congestion of the vessels of
      the eyeball, conjunctivitis, congestion and edema of the membrana nictitans,
      edema of the eyelids, accompanied by a thick, yellowish white mucus or
      mucopurulent exudate. In certain cases corneal ulcers and extensive corneal
      opacities developed. From all cases a characteristic diplobacillus was obtained.
      The organism was usually observed in the exudate in large numbers. The
      morphology, the hemolytic properties, and the proteolytic activities readily
      assist in its identification. Instillation of a few drops of bouillon suspensions
      of pure cultures beneath the eyelids of normal cattle gave rise to characteristic
      inflammations. The organism is not pathogenic for laboratory animals.

PMID- 19868780
TI  - STUDIES ON PNEUMOCOCCUS IMMUNITY : II. ACTIVE IMMUNIZATION OF MONKEYS AGAINST
      PNEUMOCOCCUS TYPES II, III, AND IV PNEUMONIA WITH THE HOMOLOGOUS PNEUMOCOCCUS
      VACCINE.
AB  - 1. Three subcutaneous injections of Pneumococcus Type II vaccine confer on
      monkeys a complete immunity against experimental Pneumococcus Type II pneumonia.
      A similar protection can be bestowed on monkeys against Pneumonococcus Type IV
      pneumonia by three subcutaneous injections of a vaccine prepared from the same
      strain of pneumococcus. 2. The subcutaneous injection of monkeys with three doses
      of Pneumococcus Type III vaccine confers a complete immunity against this type in
      only 50 per cent of cases (four out of eight monkeys vaccinated). 3. In spite of
      the immunity induced in monkeys by three subcutaneous injections of Pneumococcus
      Types II, III, and IV vaccine, specific protective bodies against the homologous
      types are not demonstrable in their serums when the vaccine is so administered.

PMID- 19868781
TI  - STUDIES ON PNEUMOCOCCUS IMMUNITY : III. THE NATURE OF PNEUMOCOCCUS ANTIGEN.
AB  - 1. Active immunity against many lethal doses of Pneumococcus Types I, II, and III
      may be produced in mice by two or three subcutaneous injections of the homologous
      type of pneumococcus saline vaccine. 2. Mice may be actively immunized with the
      protein fraction obtained by treating pneumococci with anhydrous sodium sulfate
      or by solution of pneumococci in bile salts and precipitation with alcohol.
      Pneumococcus antigen is therefore carried within or adheres to the protein
      fraction of the organism. 3. Pneumococcus antigen is resistant to prolonged
      autolysis and to tryptic digestion, and can be recovered from the soluble
      portions of digests of either the intact bacteria or the bacterial protein. 4.
      The antigen may be isolated from each of the three fixed types of pneumococcus by
      tryptic digestion of the pneumococci and extraction of the digest with 70 to 90
      per cent alcohol. The antigen is not soluble in absolute alcohol, nor is it
      soluble in ether or in the other lipoidal solvents. 5. The immunizing property of
      slightly acid solutions of the antigen is not impaired by boiling for 5 minutes,
      nor by heating at 56 degrees C. for 1 hour. Sterile unpreserved solutions of the
      antigen did not deteriorate by standing in the refrigerator for 3(1/2) months. 6.
      The exact chemical nature of pneumococcus antigen still remains to be determined.
      From the experiments reported it appears that the antigen is non-lipoidal, that
      it probably adheres to the protein fraction in a loose chemical or physical union
      rather than representing a protein complex of a large molecular size, as shown by
      its solubility in alcohol, its thermostability, and its resistance to proteolytic
      digestion. 7. Some of the antigens studied have been shown to contain a non
      specific factor promoting the growth of bacteria. 8. The purified pneumococcus
      antigen solutions are non-toxic for mice.

PMID- 19868782
TI  - CONDITIONS DETERMINING THE TRANSPLANTABILITY OF TISSUES IN THE BRAIN.
AB  - In confirmation of Shirai's observation, we find that transplantable mouse tumors
      grow actively when inoculated into the brains of rats, guinea pigs, and pigeons,
      whereas subcutaneous or intramuscular grafts in the same animals fail. This
      growth of foreign tissue in the brain, however, takes place only when the grafted
      material lies entirely in the brain tissue; if it comes in contact with the
      ventricle a cellular reaction takes place with resultant destruction of the
      graft. The growth of foreign tissue in the brain may be completely inhibited by
      simultaneous inoculations of a small bit of autologous but not by a bit of
      homologous spleen tissue. Mice highly immune to subcutaneous transplants of mouse
      cancer show no resistance to such tumors when the inoculation is made into the
      brain. Although the brain is without obvious power of resistance to implants of
      transplantable heteroplastic mouse tumors, yet grafts of spontaneous tumors fail
      to grow there even, as a rule, when tumor implanted and animal host are of the
      same species.

PMID- 19868783
TI  - STUDIES ON THE ENZYMES OF PNEUMOCOCCUS : IV. BACTERIOLYTIC ENZYME.
AB  - 1. Pneumococci possess an active intracellular enzyme which causes lysis of heat
      killed pneumococci of the same and heterologous types and to a less degree of a
      closely related organism, Streptococcus viridans. 2. The optimum reaction for
      lysis lies between pH 6 and 8. 3. The bacteriolytic action is proportional to the
      concentration of the enzyme. 4. Heating the enzyme for 30 minutes at 60 degrees
      C. destroys its activity. 5. The possible relation of the enzyme to autolysis is
      discussed.

PMID- 19868784
TI  - STUDIES ON BACTERIAL NUTRITION : IV. EFFECT OF PLANT TISSUE UPON GROWTH OF
      PNEUMOCOCCUS AND STREPTOCOCCUS.
AB  - In previous papers it has been shown that unheated plant tissue, in the form of
      potato, contains the two factors necessary for the growth of organisms of the
      hemoglobinophilic group. Further studies (5) confirmed these findings and showed
      that yellow and white turnip, carrot, beet, parsnip, and sweet potato can replace
      blood in the cultivation of Bacillus influenzae. In the present paper it has been
      shown that vegetable tissues also greatly facilitate and stimulate the growth of
      other organisms entirely unrelated to Bacillus influenzae. Three varieties of
      Gram-positive cocci have been used in the present study, pneumococcus,
      Streptococcus hamolyticus, and Streptococcus viridans. With pneumococcus it has
      been previously shown that prompt and luxuriant growth will occur in broth
      containing unheated potato even though the seeding be so small that no growth
      whatever will occur with the same seeding in plain broth (5). In the present
      study it has been shown that even in dextrose broth this minimal inoculation is
      followed by a prolonged period of lag, whereas in potato broth this same inoculum
      serves to initiate immediate and rapid growth. When pneumococci are grown in
      potato broth not only is the period of lag abolished, but the stationary period
      of growth is extended and cell death is delayed. Moreover, in plant tissue medium
      the zone of hydrogen ion concentration within which growth of pneumococcus can be
      initiated is considerably extended beyond the acid and alkaline limits of the
      optimal range in ordinary bouillon. It has been found also that the presence of
      unheated plant tissue in the media likewise stimulates growth of hemolytic and
      non-hemolytic streptococci. In this investigation no attempt has been made to
      determine the exact nature of the substances in plant tissue upon which these
      properties depend. That they are not of the nature of readily fermentable
      carbohydrates, however, is made evident by the fact that no increased production
      of acid occurs in the pneumococcus culture when potato is present.

PMID- 19868785
TI  - THE COMPLEMENT FIXATION REACTION AS APPLIED TO LEPROSY.
AB  - By means of a method differing in important details from those of previous
      investigators it has been determined that the blood serum of cases of leprosy
      exhibits the ability to fix complement with a wide variety of antigens including
      to a greater or less extent those derived from any culture of the acid-fast group
      of bacteria available to us. This property of multiple fixation may sufficiently
      characterize the disease to be of diagnostic significance, although our
      experience is hardly sufficient to enable us to speak with complete assurance on
      this point. Certainly, control sera from normal individuals, from cases of
      tuberculosis, or from cases of syphilis as obtained in our locality have entirely
      failed to react with certain antigens, whereas serum from cases of leprosy have
      so reacted to the extent of over 93 per cent. The most characteristic fixation
      given by the leprosy sera is that with Bacillus leprae (Clegg) used as antigen,
      either in the form of a bacterial emulsion or of an alcoholic extract of the
      dried culture. Antibody absorption may be demonstrated in the acid-fast group if
      the absorbing bacteria are removed by filtration. Otherwise the resulting fluid
      is strongly anticomplementary. Leper serum is not deprived of the complement
      fixing body when so treated with either Bacillus tuberculosis or Bacillus leprae
      (Clegg).

PMID- 19868786
TI  - LEISHMANIA DONOVANI IN THE PERIPHERAL BLOOD.
AB  - 1. The effect of human red cells and serum on the growth of Leishmania donovani
      has been studied and a blood culture method devised, based on these findings. 2.
      The distribution of blood platelets and of the different varieties of leucocytes
      in the strata of centrifugalized diluted blood has been investigated, and also
      the distribution of Leishman-Donovan bodies, extracellular and intracellular, in
      these strata. 3. The effect of treatment with antimony on the cultivability of
      Leishmania donavani has been studied.

PMID- 19868787
TI  - MESENCHYME AND MESOTHELIUM.
AB  - The migratory mesenchymal cells in cultures of the embryonic chick heart show all
      stages of transformation from the bipolar and multipolar reticular cells to the
      flat mesothelial forms. One can actually observe this change in form. Such
      mesothelial cells seem to differ from the mesenchymal cells only in form and not
      in structure, indicating that mesothelium is to be considered not as a tissue
      differentiated from the mesenchyme, but merely as a change or transformation in
      form. These observations, together with those of W. C. Clarke, indicate that, in
      the healing of wounds of the mesothelium lining the peritoneal, pleural, and
      serous cavities, new mesothelium may arise from the subjacent mesenchyme by the
      change in form of its cells, and that the repair after abrasions of the
      mesothelium is not necessarily brought about by a spreading of the adjacent
      mesothelium over the wound, such as occurs in repair of skin wounds.

PMID- 19868788
TI  - STUDIES ON ENDOTHELIAL REACTIONS : VIII. CHANGES IN THE DISTRIBUTION OF TUBERCLE
      BACILLI AND TUBERCLES IN THE ORGANS OF RABBITS FOLLOWING SPLENECTOMY.
AB  - If the spleen be removed from rabbits and tubercle bacilli be injected
      intravenously, it is found that the lesions produced differ materially from those
      observed in control animals; the lungs present the most marked contrast, the
      liver also shows a definite difference in the distribution of the tubercles, and
      the kidney lesions also differ in the two instances. In discussing these facts we
      must answer, if possible, the four questions formulated above. It appears that
      the pulmonary lesions in Group S are small and discrete because of some
      inhibitory factor that prevents the diffusion of the products of dead tubercle
      bacilli. The organisms, far from being killed, are more numerous and better
      preserved in this group, but their destructive action is localized. This seems to
      be connected with the presence of polymorphonuclear leucocytes, for these cells
      are more numerous in the lesions and more plentiful in the lumina of the
      pulmonary capillaries of Group S than they are in the controls. The conclusion to
      be drawn from this covers the answer to the second question. It is not the
      tubercle bacillus itself that produces the destructive changes, but the toxins
      liberated by the breaking down of its substance. The well known experiments of
      Hodenpyl and Armand-Delille, already referred to in this series of papers, show
      this to be true; dead tubercle bacilli, or even extracts of these organisms, will
      produce typical tubercles. Removing the spleen stimulates the production of
      polymorphonuclear leucocytes, as shown by Johnstone (1922). These cells may
      prevent the diffusion of split products from the bacilli by removing or
      neutralizing them. The third question, as to why the liver is more affected after
      splenectomy than in normal controls, is more readily answered. Probably the
      spleen acts as a catch-basin for the bacteria; once removed it can no longer
      withhold them from the portal circulation and the liver receives a larger number
      than it would were this bacterial filter still operative. On the other hand,
      there may be an increase in the phagocytic activity of the endothelium of the
      sinusoids which might take up more bacteria under these changed conditions.
      Several investigators have claimed, recently, that there is an increased activity
      of the liver endothelium following splenectomy, their experiments being directed
      chiefly toward determining the fate of the erythrocytes. Pearce (1918) in
      reporting the effects of experimental splenectomy in dogs, states that there are
      definite compensatory changes in the lymph nodes, in the form of an increased
      proliferation of endothelial phagocytes, and that the stellate cells of the liver
      sinusoids often show a similar compensatory increase in number. In both cases the
      cells are, apparently, formed in situ rather than transported to the organs. He
      says: 'Such findings suggest the development of a compensatory function on the
      part of the lymph-nodes and possibly the liver,' and suggests that, in times of
      stress 'the stellate cells of the liver thus assume, in part at least, the
      function of destroying red blood-corpuscles by phagocytosis.' Incidentally, he
      presents an excellent discussion of the history and subject of splenectomy.
      Motohashi (1922) reports a great increase in the hemophagic power of the hepatic
      endothelium and an increase in the number of endothelial elements, after some 45
      days following splenectomy in rabbits. Nishikawa and Takagi (1922) have observed
      similar phenomena with white rats, the Kupffer cells taking up erythrocytes in
      large numbers in splenectomized animals, whereas controls never show similar
      propensities on the part of these cells. It may be that different substances
      cause different reactions on the part of the hepatic endothelium. Contributory
      Experiment.-A side experiment was performed with five rabbits, two splenectomized
      and three controls, into which uniform doses of pneumococci were injected
      intravenously. They all died of septicemia after a few days. The results of this
      experiment strengthen the foregoing conclusions materially. It was found that
      there were many polymorphonuclear amphophils in the pulmonary capillaries of the
      splenectomized animals and that there were numerous focal necroses in the livers.
      The controls showed much fewer polymorphonuclear cells in the lungs and no focal
      necroses in the livers, while the spleens were actively congested and inflamed.
      Otherwise the experiment was not of sufficient importance to warrant a separate
      report. The question as to why the endothelium of the pulmonary capillaries shows
      no stimulation similar to that observed in the carbon experiment, but rather less
      activity than that of the controls, must be answered hypothetically for the
      present. With the carbon, comparatively huge amounts of foreign matter were
      injected repeatedly; here but one injection of a much smaller amount of suspended
      tubercle bacilli was administered. The resulting stimulus to the pulmonary
      endothelium would, therefore, differ materially in the two instances. In one
      there would be succeeding waves of stimulation following each injection of
      irritating foreign substance. In the other an entirely different sort of stimulus
      would result; the bacteria would be withdrawn from the circulation within an hour
      or two, judging by past experience, and would then multiply, to be cast off into
      the circulation in driblets, as the lesions containing them broke down. At least
      it can be said that there is a good theoretical reason for the difference in the
      endothelial reaction in the lungs of the two groups of animals.

PMID- 19868789
TI  - THE EFFECT OF PEPTONE ON THE PERIPHERAL CIRCULATION.
AB  - 1. Injection of a solution of peptone directly into the artery of the leg of a
      dog is followed by an abrupt increase in leg volume. This is of short duration
      and is quickly followed, usually in less than (1/2) minute, by a decrease in the
      volume of the limb below that previous to the injection. 2. The phases of the leg
      volume curve bear a fairly definite relation to the changes in arterial pressure.
      3. These results, therefore, indicate that the long continued low arterial
      pressure in peptone shock, and probably in anaphylactic shock, may be hastened
      but is not maintained by peripheral dilatation, and suggest that there is an
      impounding of the blood in some other part of the body.

PMID- 19868790
TI  - PROTECTION AGAINST TYPHOID-LIKE INFECTIONS BY VACCINATION : AN EXPERIMENTAL
      STUDY.
AB  - 1. A natural infection of guinea pigs with the "mutton" strain of Bacillus
      aertrycke was used to test the protective power of vaccination against the
      typhoid group of infections. 2. Under the conditions of the experiment, complete
      protection was secured by vaccination with full strength fresh saline vaccine,
      while 100 per cent of deaths occurred among the controls. 3. The immunity
      acquired is variable and depends on the number of organisms injected. 4. Vaccine
      kept 10 to 14 months gave less protection than vaccine 8 months old and under. 5.
      Saline vaccine was more effective than lipovaccine, sensitized vaccine, or
      supernatant fluid vaccine. 6. Resuspended vaccine was as effective as the
      original vaccine. 7. In one experiment, group vaccine, made of typhoid Para A and
      Para B bacilli, was as effective as the original specific vaccine.

PMID- 19868791
TI  - OXIDASE REACTION OF VARIOUS GROUPS OF BACTERIA.
AB  - 1. A simple technique is described for studying the oxidase action of bacteria by
      means of the oxidation of p-aminoleucomalachite green. 2. It is shown that
      pneumococci under aerobic conditions produced an oxidase when grown on suitable
      medium. The sera of any of seven different animal species constitute such a
      medium, the degree of oxidation by the pneumococcus depending upon the animal
      from which the serum was taken-rat, guinea pig, rabbit, horse, man, cat, and
      chicken in order of diminishing suitability. 3. Conditions favoring the oxidation
      of p-aminoleucomalachite green by a single strain of pneumococci are: the
      presence of a slight amount of hemoglobin, dextrose, H ion concentration on the
      add side, and heating of fresh serum for 30 minutes at 56 degrees C. Conditions
      preventing the oxidation are: sterilized meat infusion, 1 per cent peptone, plain
      broth, a high concentration of hemoglobin, and absence of oxygen. In a
      quantitative fashion, meat infusion, 1 per cent peptone, and plain broth
      interfere with the suitability of serum as a substratum of oxidase production by
      the pneumococcus. 4. Twenty-three microbic species were studied with reference to
      oxidative power. They were grown upon 10 per cent horse serum, with and without
      dextrose, upon 10 per cent guinea pig serum, and upon plain broth. Only three of
      the twenty-three gave evidence of oxidative power as tested by p
      aminoleucomalachite green; namely, the pneumococcus, Streptococcus viridans, and
      Streptococcus haemolyticus. Among the strains, of these three pneumococci gave
      the most intense reaction, after which Streptococcus viridans and Streptococcus
      haemolyticus follow in the order named, but with a noticeable variation among the
      different strains of Streptococcus haemolyticus. 5. Hemolytic streptococci of
      human and bovine origin were studied. The only variation in the type of reaction
      was manifested by the streptococci of milk and cheese origin. Strains from these
      sources showed definitely the least oxidase activity. Streptococci from mastitis
      and cow's udder were indistinguishable by the test from the hemolytic
      streptococci of human origin.

PMID- 19868792
TI  - STUDIES ON X-RAY EFFECTS : XIII. HISTOLOGICAL STUDY OF THE FATE OF CANCER GRAFTS
      INOCULATED INTO AN X-RAYED AREA.
AB  - Cancer cells implanted in a skin region previously exposed to an erythema dose of
      x-rays show a series of degenerative changes in every way comparable to the
      frequently described stages of cancer cell degeneration following x-ray
      treatment. The findings contrast strongly with the survival and growth of grafts
      implanted in unexposed regions in the same animal. Since the changes are the same
      whether the cancer cells have been directly exposed in situ or merely implanted
      in the previously exposed skin, it follows that it is impossible to establish
      microscopically a direct injury from the x-raying as the principal factor in the
      therapeutic action of x-rays on cancer.

PMID- 19868793
TI  - STUDIES ON LYMPHOID ACTIVITY : VII. SUPPRESSION OF INDUCED IMMUNITY TO
      TRANSPLANTED CANCER BY LARGE DOSES OF OLIVE OIL.
AB  - The state of potential immunity to transplanted cancer engendered in mice by an
      injection of homologous blood may be reversed and converted into a susceptible
      state by an intraperitoneal injection of olive oil prior to the cancer
      inoculation. The suppression of resistance is accompanied by the failure of
      certain cellular reactions known to develop during the establishment of immunity
      to transplanted cancer.

PMID- 19868794
TI  - BOTULISM. STUDIES ON THE MANNER IN WHICH THE TOXIN OF CLOSTRIDIUM BOTULINUM ACTS
      UPON THE BODY : II. THE EFFECT UPON THE VOLUNTARY NERVOUS SYSTEM.
AB  - 1. In addition to the effect upon the fibers of the parasympathetic nervous
      system which was described in a previous report (1), the toxin of Clostridium
      botilinum. Types A and B, exerts an influence upon the endings of the motor
      fibers of the voluntary nervous system which leads to a marked susceptibility to
      fatigue. It has not been determined whether the damage is in the anatomical nerve
      endings of the somatic motor nerve fibers or upon the myoneural junction, but it
      is not of the nature of an organic destruction of tissue. 2. There is no effect
      upon the sensory fibers of the peripheral nerves. 3. The muscle cells of the
      smooth and striated muscles are not affected. 4. The disturbances in function
      which have been demonstrated in the voluntary and involuntary nervous systems
      fully explain the characteristic signs and symptoms of botulinus intoxication.

PMID- 19868795
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : V. METASTASES. PART 1.
      DESCRIPTION OF THE LESIONS WITH ESPECIAL REFERENCE TO THEIR OCCURRENCE AND
      DISTRIBUTION.

PMID- 19868796
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : V. METASTASES. PART 2.
      DESCRIPTION OF THE LESIONS WITH ESPECIAL REFERENCE TO THEIR OCCURRENCE AND
      DISTRIBUTION.
AB  - As a part of a general investigation of a malignant tumor of the rabbit, the
      phenomena of metastasis were studied in a group of 191 animals. The results of
      this investigation are presented from the standpoint of the relation of
      metastasis to animal resistance. The incidence and distribution of different
      classes of lesions are given and the peculiarities of the growth in different
      organs and tissues are described with especial reference to the time and
      circumstances of their occurrence and the relation of metastases in one organ or
      tissue to those of another. It was found that while the picture presented by
      different animals varied greatly, there was a remarkable degree of uniformity in
      the character of the lesions in a given organ or tissue and in the circumstances
      under which metastases occurred in a given location. It was thus possible to
      establish a relationship between the distribution of metastases and the function
      of animal resistance. In brief, the conclusion was reached that the peculiarities
      of metastatic involvement displayed by individual animals were not entirely
      attributable to chance distribution of tumor cells but that they were founded
      very largely upon constitutional differences and that the picture presented in
      any given instance represented an expression of the interaction between tumor and
      host, the character and force of which were indicated by the nature and
      distribution of the lesions or by the organs and tissues affected.

PMID- 19868797
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : V. METASTASES. PART 3. FACTORS
      THAT INFLUENCE OCCURRENCE AND DISTRIBUTION.
AB  - Data bearing on the occurrence and distribution of metastases, as recorded in the
      preceding papers of the series, are analyzed with reference to the parts played
      by the tumor cell and by conditions which influence cell distribution and cell
      growth. It is shown that, while the tumor cell is an essential element in the
      production of metastases, its influence is relatively constant, and that the
      prime factors responsible for variations in the occurrence and distribution of
      metastatic growths are conditions that influence cell distribution or that affect
      the viability of the cell during transport, and conditions that affect the
      nutrition of the cell wherever it may become lodged. It is further shown that
      both the presence and the absence of metastases, as well as peculiarities of
      distribution and of growth, are susceptible of a comparatively simple explanation
      upon the basis of well recognized principles of pathological action. In brief, it
      was found that, while the tumor cells might be distributed by either the blood
      stream or the lymphatics, the mode of distribution and the fate of the cells were
      determined in accordance with the same general principles that are applicable to
      the distribution and disposal of foreign cells introduced into the animal body.
      It was pointed out, however, that in applying these principles to tumor
      metastasis, it was necessary to recognize the fact that tumor cells bear a
      definite relation to the tissues of the host and that they are living and
      agressive agents. Hence, the reaction that they arouse differs in some respects
      from that produced by inert or unorganized foreign material or by living cells of
      a foreign species.

PMID- 19868798
TI  - A METHOD FOR THE PHYSIOLOGICAL STUDY OF TISSUES IN VITRO.
AB  - 1. A method has been developed which allows the continuous growth of pure strains
      of fibroblasts, epithelium, and leucocytes in a medium which undergoes but slight
      spontaneous deterioration. 2. The principle of the method is to leave the tissues
      undisturbed while the medium is changed. This was realized by special containers
      allowing the change of the medium without bacterial contamination and by the
      simultaneous use of a solid and a fluid medium. 3. The curve of growth of pure
      cultures of fibroblasts and epithelial cells in a nutrient medium is a parabola;
      in a non-nutrient medium, it is S-shaped and expresses the residual activity of
      the tissues. Leucocytes invade the culture medium progressively, as do bacteria,
      but never aggregate in a tissue. 4. The method is used for the study of the
      morphological and dynamic changes occurring in tissues under the influence of
      chemical and physical factors.

PMID- 19868799
TI  - ANTAGONISTIC GROWTH PRINCIPLES OF SERUM AND THEIR RELATION TO OLD AGE.
AB  - IT MAY BE CONCLUDED THAT, UNDER THE CONDITIONS OF THE EXPERIMENTS: 1. The
      inhibiting action on homologous fibroblasts of the heated serum of a young animal
      increases relatively more than that of an old animal. After it has been heated,
      the inhibiting action of the serum of the old animal is still greater than that
      of the young animal. 2. The CO(2) precipitate obtained from the serum of a young
      animal definitely increases the proliferative activity of homologous fibroblasts,
      while the CO(2) precipitate of the serum of an old animal has practically no
      activating power. After the removal of the CO(2) precipitate, the inhibiting
      action of the serum of young animals is increased, while that of old animals is
      not modified. 3. The increased inhibiting action of serum on homologous
      fibroblasts in old age is partly due to the disappearance of the growth
      activating substances and to the enhanced activity of the growth-inhibiting
      principle.

PMID- 19868800
TI  - STUDIES ON THE NASOPHARYNGEAL SECRETIONS FROM PATIENTS WITH COMMON COLDS.
AB  - From the foregoing experiments it appears that with the filtered nasopharyngeal
      secretions from early cases of typical infections common colds in the first 3 to
      18 hours of the disease, a similar condition can be transmitted to man. With the
      unheated but not with the heated secretions from four of six such patients we
      have succeeded in transmitting an affection indistinguishable from common cold to
      four men and in two instances the condition was conveyed from the person with the
      experimental disease to a second individual -in all, therefore, to six supposedly
      normal subjects. The periods of incubation in the experimental disease varied
      from 8 to 48 hours. We failed to obtain these results with the filtered
      secretions from cases of common colds 18 and 20 hours after the onset of symptoms
      and from a patient with the experimental disease 20 hours after the first
      symptoms. It would appear that the secretions are more active in the early hours
      of the affection. We also failed in the two instances in which colds were caused
      by exposure to the elements, or chilling of the body, and not by definite contact
      with other cases of common colds. Intratracheal inoculations in rabbits with
      unfiltered and filtered nasopharyngeal washings obtained from patients with
      common colds induce no characteristic or distinctive effects on the tissues, from
      which no constant, pathogenic agent has, as yet, been recovered. In comparison,
      similar material from cases of epidemic influenza do, however, cause particular
      changes in the blood and lungs of these animals, cultures of the lungs often
      yielding Bacterium pneumosintes. In view of these facts and since the clinical
      pictures exhibited by these diseases differ, the conclusion may be drawn that
      infectious common colds and epidemic influenza are separate and distinct
      diseases. On the other hand, the negative results obtained with materials derived
      from common colds and from parallel series of experiments with secretions from
      supposedly healthy persons, serve as a control to the effects produced with the
      nasopharyngeal washings obtained from influenza patients. Aerobic and anaerobic
      cultures of the filtered nasopharyngeal washings from 40 early cases of
      infectious common colds have thus far yielded no constant, pathogenic agent which
      can be regarded as the incitant of the disease. The filtered washings of nineteen
      cases were studied by the combined method of Smith-Noguchi fluid medium and
      anaerobic blood agar plates. In these instances representatives of the three
      groups of anaerobic filter-passing, Gram-negative bacteria, described by Olitsky
      and Gates were cultured from twelve patients. The irregularity of their
      occurrence not only in common colds but in influenza and supposedly normal
      persons and their lack of pathogenicity for rabbits and man indicate that these
      bacteria are not peculiar to common colds. This method has opened to view a
      number of hitherto undescribed microorganisms which can be found in different
      respiratory affections and in health. Furthermore, by morphological, cultural,
      and serological means, the separation into distinct species of each of these
      groups of bacteria has again been demonstrated. It is noteworthy that Bacterium
      pneumosintes was not found in any of the cultures from the 40 patients. Special
      attention was given to the detection of elements similar to Foster's globoid
      bodies in the cultures derived from common colds and from the experimental
      disease in man, and from the lungs of inoculated rabbits. We have not been able
      to determine the presence of these bodies, although the precipitate which forms
      in fresh rabbit kidney tissue-ascitic fluid medium was illusory in such relation
      since it was a common experience to find this precipitate simulating the globoid
      bodies of poliomyelitis. Still more disturbing is the fact, that these particles
      could be carried over from subplant to subplant and even showed pseudo colony
      formation in the Noguchi semisolid medium in tubes. But when the particles were
      put to rigorous test for a living and multiplying organism, the tests failed to
      reveal multiplication. The increasing importance of the tissue-ascitic fluid
      medium in bacteriological technique warrants a detailed description of the
      requirements necessary for the determination of the living nature of formed
      elements in cultures in this medium, (a) No one method of staining can be relied
      upon, for stain precipitate in itself adds to the confusion. A specimen for
      examination should be stained separately by Gram's and Giemsa's methods and with
      another nudear dye, such as polychrome methylene blue. As a rule, microorganisms
      will reveal their morphological characters in more than one stain, whereas
      precipitate may be found in only one and not in the others. The experienced eye
      will discern the precipitated particles in selected parts of the stained
      preparation where they often occur in enormous numbers, clumped into irregular
      masses of varying forms from the periphery of which there is a gradual fading out
      to finer, more uniform structures. (b) In addition, suspected growths should be
      tested in the dialysate medium of Gates since by this method the precipitated
      material of the medium is kept from admixing with the growth, and a clear view of
      any microorganisms, if present, is obtained, (c) Another requirement is colony
      formation of the suspected culture. This is an absolute essential and can be
      effected by planting the material to be tested on solid plate media, incubated
      aerobically, and anaerobically in Brown's jar. Semisolid medium in long tubes
      should also be employed but care is needed to avoid mistaking small particles of
      precipitate for actual colonies of bacteria. To make certain of growth of
      microorganisms in semisolid medium, however, subplanting to a precipitate-free,
      dialysate medium is required. By following this method minute microorganisms
      which are obscured, or simulated, by precipitate in the Smith-Noguchi medium, can
      be identified.

PMID- 19868801
TI  - A METHOD FOR THE DETERMINATION OF THE SPECIFIC GRAVITY OF RED BLOOD CELLS.
AB  - 1. A simple method for determining the specific gravity of red blood cells is
      described. 2. It is more rapid than and as accurate as pycnometer determinations.
      3. The marked chemical and physical interactions between corpuscles and
      suspension fluids in other methods are avoided.

PMID- 19868802
TI  - THE LUNG VOLUME IN HEART DISEASE.
AB  - The lung volumes in a group of individuals suffering from chronic cardiac disease
      have been studied by a method which is applicable to patients suffering from
      dyspnea. In a number of instances the same patients were investigated during
      various stages of decompensation and compensation. The values found have been
      compared with those determined in a group of normal subjects. Lung volumes have
      been considered from three points of view: (1) relative lung volumes or
      subdivisions of total lung volume expressed as percentage of total lung volume;
      (2) the absolute lung volumes of patients with heart disease have been compared
      with lung volumes calculated for normal individuals having similar surface areas
      or chest measurements; and (3) in individual cases absolute lung volumes have
      been measured in various stages of compensation and decompensation. (1) In
      patients with heart disease it has been observed that the vital capacity forms a
      portion of the total lung volume relatively smaller than in normal individuals,
      and that the mid-capacity and residual air form relatively larger portions. When
      the patient progresses from the compensated to the decompensated state these
      changes become more pronounced. (2) When the absolute lung volumes determined for
      patients are compared with volumes of the same sort, as calculated for normal
      individuals of the same surface areas and chest measurements, the following
      differences are found. The vital capacities are always smaller in the patients
      and the volumes of residual air are always larger. There is a tendency for middle
      capacity and total capacity to be smaller, though, when the patients are in a
      compensated state, these volumes may approximate normal. (3) When decompensation
      occurs the absolute lung volumes undergo changes as follows: (a) vital capacity,
      mid-capacity, and total capacity decrease in volume; and (b) the residual air may
      either increase or decrease according to the severity of the state of
      decompensation. The significance of these changes has been discussed and an
      explanation offered for the occurrence of a residual air of normal volume in
      patients with heart disease. It results from a combination of two tendencies
      working in opposite directions: one to increase the residual air-stiffness of the
      lungs (Lungenstarre); the other to decrease it-distended capillaries
      (Lungenschwellung), edema, round cell infiltration.

PMID- 19868803
TI  - CHEMICAL CHANGES IN THE BLOOD OF THE DOG AFTER OBSTRUCTION OF THE ESOPHAGUS AND
      OF THE CARDIAC END OF THE STOMACH.
AB  - Ligation of the cardiac end of the stomach or of the esophagus in ten dogs
      produced a severe toxemia, and rapid death. In seven of the animals there
      occurred a marked rise in the total non-protein nitrogen and urea nitrogen of the
      blood. The dogs living longest with cardiac obstruction showed a fall in blood
      chlorides and a rise in the CO(2)-combining power of the plasma. All the dogs
      with an obstruction of the esophagus showed a fall in blood chlorides. Control
      animals subjected to other types of abdominal operations showed no significant
      changes in the blood.

PMID- 19868804
TI  - SURVIVAL AND GROWTH OF FIBROBLASTS IN VITRO.
AB  - When multiplying actively in serum, fibroblasts are in a condition of survival,
      not of cultivation, for they do not synthetize protoplasm from substances
      contained in the medium. They are able to utilize only the nitrogenous material
      stored in the tissue itself. The distinction between survival of tissue and
      active growth is an important one. Innumerable errors in the interpretation of
      the experimental results have been made during the past years on account of this
      lack. An active proliferation of fibroblasts taking place during several days in
      a medium containing a given substance does not mean that this substance is used
      by the cells, but indicates only that residual cell proliferation is unopposed by
      a toxic substance. It is not possible to ascertain whether a medium is nutrient
      or not in the sense that it supports growth unless the mass of the tissues is
      shown to increase. When the proliferating fragment can be halved again and again,
      and each half reaches the size of the original whole in 48 hours, it is evident
      that new protoplasm must have been synthetized from the medium. The experiments
      described above show that egg white, egg yolk, pure egg albumin, egg white mixed
      with egg yolk, and bouillon are not utilized by fibroblasts for multiplication.
      This fact renders more plausible the hypothesis advanced previously that for
      proliferation the fibroblasts require some nitrogenous substances elaborated by
      other cells, which are present in embryonic tissue juices. It may be concluded
      that, under the conditions of the experiments: 1. The duration of life of pure
      cultures of fibroblasts in a nitrogen-free medium is about 8 days. 2. Egg white
      and egg yolk, isolated or together, slightly increase the activity of the
      fibroblasts, but this effect is temporary and the tissues ultimately die. Pure
      egg albumin and bouillon are not utilizable by fibroblasts for multiplication.

PMID- 19868805
TI  - ACTION ON FIBROBLASTS OF EXTRACTS OF HOMOLOGOUS AND HETEROLOGOUS TISSUES.
AB  - Extracts of homologous adult tissues detemine an increase in the mass of pure
      cultures of chicken fibroblasts nourished thereon comparable to that resulting
      from embryonic tissue juice. But the effect of these extracts differs markedly
      from that of the latter, since cell multiplication does not continue
      indefinitely. After a few passages, the fibroblasts cultivated in adult tissue
      extracts grew more slowly than in Tyrode solution. The cytoplasm became dark and
      filled with fat granules, and death followed. It is possible that the tissues of
      adult animals contain, as does the serum, substances which are toxic for the
      homologous cells, and which progressively overcome the effect of the growth
      activating substances. The effect of heterologous adult tissue extracts did not
      differ markedly from that of homologous tissues. The chicken connective tissue
      increased slightly in mass, but died sooner than the controls in Tyrode solution.
      By contrast, tissue juices derived from the embryos of mice, guinea pigs, and
      rabbits acted on chicken fibroblasts in the same manner as chick embryo juices.
      The increase in mass of the cultures was regular and rapid. They doubled in size
      every 48 or 72 hours, and the rate of growth did not decrease after 30 days. It
      appears that embryonic tissue juices are not necessarily toxic for heterologous
      fibroblasts, and that they can be used in the building up of protoplasm in the
      tissues of a different species. In experiments made long ago, the action of
      tissue juice was described as being specific. The premature death of the
      fibroblasts cultivated in heterologous juices at that time would now appear to
      have been due to spontaneous changes in the pH and the deterioration that even
      normal chick embryo juice at a pH of 7.8 undergoes spontaneously. In the recent
      experiments, when freshly prepared homologous and heterologous juices were used,
      their action on chicken fibroblasts in pure culture was identical. However, the
      fibroblasts produced in cultures nourished by rabbit juice grew better when
      transferred to rabbit serum than did ordinary chicken fibroblasts. It has not
      been determined as yet whether this effect is due to an immunization of the
      fibroblasts against rabbit humors, or to some decrease in the specificity
      eventuating in cells intermediate between rabbit and chicken fibroblasts. It may
      be concluded that, under the conditions of the experiments : 1. Pure cultures of
      chicken fibroblasts increase in mass under the influence of extracts of adult
      homologous tissues. But they ultimately die while the fibroblasts cultivated in
      embryonic tissue juices live indefinitely. 2. The increase in mass of chicken
      fibroblasts cultivated in the juices of mouse, guinea pig, rabbit, and chick
      embryos is about identical. 3. Chicken fibroblasts produced in cultures nourished
      by rabbit embryonic tissue juice are less sensitive to the inhibiting action of
      rabbit serum than ordinary chicken fibroblasts. 4. Cultures of chicken
      fibroblasts in extracts of adult tissues of mice, guinea pigs, and rabbits
      increase slightly in mass, but the increase is temporary and death occurs after a
      few passages.

PMID- 19868806
TI  - ACTION OF SERUM ON LYMPHOCYTES IN VITRO.
AB  - IT MAY BE CONCLUDED THAT, UNDER THE CONDITIONS OF THE EXPERIMENTS: 1. Lymphocytes
      and large mononuclear cells can live and increase greatly in numbers in blood
      serum, while fibroblasts are not capable of doing so. 2. While living in serum,
      lymphocytes and large mononuclear cells manufacture and secrete substances which
      may be used as food material by the fibroblasts. 3. It is probable that
      lymphocytes and large mononuclear cells synthetize from the nitrogenous compounds
      contained in serum the substances which fibroblasts and epithelial cells require
      for their multiplication.

PMID- 19868807
TI  - MEASUREMENT OF THE INHERENT GROWTH ENERGY OF TISSUES.
AB  - 1. The residual growth energy of fibroblasts is expressed by the extent of their
      migration and multiplication in a non-nutrient medium. 2. The residual energy of
      fibroblasts is related to their inherent energy and the variations of the
      inherent energy can be ascertained by the measurement of the residual energy.

PMID- 19868808
TI  - BLOOD CELL FORMATION AND DISTRIBUTION IN RELATION TO THE MECHANISM OF THYROID
      ACCELERATED METAMORPHOSIS IN THE LARVAL FROG.
AB  - 1. Thyroid-accelerated metamorphosis in the larval frog is accompanied by changes
      in the hemopoietic centers and in the blood cell distribution in the various
      regions of the body. These changes are interpreted as results of the fundamental
      change in basal metabolic rate induced by the thyroid treatment. 2. There is
      initiation of the shift of hemopoietic locus from the kidney, the larval
      hemopoietic organ, to the spleen, the adult hemopoietic organ. The spleen, being
      chiefly an erythrocyte producer, becomes of greater importance with the
      transition from the lower metabolic rate to the higher, since greater
      erythropoiesis becomes necessary to supply the physical basis for the maintenance
      of the higher metabolic rate. 3. It is suggested that the appearance of red bone
      marrow in the later history of the frog is correlated with a still higher
      metabolic rate. Phylogenetically, in the vertebrate series, red bone marrow is
      also associated with higher metabolic rate. 4. The new metabolic rate initiated
      in tadpoles by thyroid administration sets up a demand for (a) erythrocytes, (b)
      granulocytes and lymphoid phagocytes for distribution to regions of regressive
      change, (c) lymphocytes, (1) as progenitors of erythrocytes, granulocytes and
      phagocytes, (2) for promoting growth of cells in regions of progressive change.
      5. Upon the hemopoietic reserve, which in the last analysis is the lymphocyte
      (and its mesenchymal precursor), depends the extent to which metamorphosis will
      proceed. Inability on the part of the hemopoietic centers, chiefly the spleen, to
      keep pace with the demand for blood cells during metamorphosis results in
      metamorphic stasis, a condition of anemia which is usually followed by death. 6.
      The growth-promoting function of leucocytes, as demonstrated by Carrel, is
      probably to be ascribed to the lymphocyte component of leucocytes. 7. The
      granulocytes have probably also a glandular function, and may exert a lytic
      effect upon adjacent tissues in regions of regressive change.

PMID- 19868809
TI  - THE INFLUENCE OF THE ADRENAL GLANDS ON RESISTANCE : I. THE SUSCEPTIBILITY OF
      ADRENALECTOMIZED RATS TO MORPHINE.
AB  - 1. The majority of rats (Mus norvegicus), because of accessory cortical tissue,
      will survive double adrenalectomy indefinitely under optimum conditions. 2.
      Resistance to morphine is greatly diminished in healthy adrenalectomized rats
      tested before hypertrophy of the accessories occurs. 3. This greater
      sensitiveness seems to be due to some fundamental alteration in metabolism
      dependent on a partial adrenal insufficiency. Protocol 1.-Rat 13; brown and
      white, male. Sept. 15, 1922. In stock. Sept. 18. Active, vigorous, and very
      vicious. Weight 281 gm. Operation, double adrenalectomy. Prompt recovery. Sept.
      21. Very active and vicious. Sept. 22. Jumps viciously this morning on opening
      the cage. This afternoon, quiet and marked diarrhea. Transferred to individual
      cage. Eating nothing. Sept. 23, Diarrhea. Quiet, Sept. 24. Diarrhea diminished,
      more active, but is not vicious. Appetite poor, ate 5 gm, Sept. 25. Diarrhea, ate
      nothing. Sept. 26. Diarrhea still marked, ate nothing. Died this afternoon.
      Autopsy.-Weight 215 gm. Thyroid, heart, and lungs normal. Abdomen: intra
      abdominal fat almost completely gone. Adrenals absent. Stomach: definite multiple
      minute hemorrhages in the mucous membrane throughout the pyloric part.
      Intestines: several loops of small gut deep red in color. Liver: nutmeg color.
      Protocol 2- Rat 43; white, male. Oct. 20, Active. Weight, 236 gm. Operation,
      excision of right adrenal and excision of piece of pancreas near left adrenal.
      Moderate bleeding. Oct. 22. Has not eaten since operation. Oct. 23. Active,
      beginning to eat. Oct. 27. Active,, eating well now. Slight diarrhea. Weight, 222
      gm. At 11:10 a.m. injected subcutaneously with 1.78 cc. of 1 per cent morphine
      sulfate solution ( = 80 mg. per kg.). 1:30 p.m., quiet. 6 p.m., recovering. Oct.
      28. Active, eating well. Nov. 10. In good condition. Sacrificed Jan. 8. Right
      adrenal absent, left adrenal intact. Protocol 3.- Rat 42; white, male. Oct. 20,
      Active. Weight, 320 gm. Operation, excision of both adrenals, much abdominal fat.
      Oct. 21. Ate 10 gm. of food. Oct. 22. Active, ate all of food (15 gm.). Oct. 27.
      Active. Weight, 310 gm. At II a.m. injected subcutaneously 0.62 cc. of 1 per cent
      morphine sulfate solution (= 20 mg. per kg.). 1:30 p.m., marked pilomotor effect.
      Did not move. 6 p.m., very quiet. Oct. 28. Very quiet, not eating. Oct. 29.
      Quiet. Ate a little today. Oct. 30. Very dull, not eating. 5 p.m., comatose. 9:30
      p.m., found dead. Autopsy.-Weight 277 gm. Diarrhea. Thyroid large and dark red.
      Heart and lungs normal. Abdomen: scant fat. Both adrenals absent. No accessories
      seen. Right testicle congested. Liver and spleen normal. Stomach: one hemorrhage
      beneath mucosa near fundus. Prolocol4.-Rat 21;white and brown,male. Sept-27.
      Active. Weight345gm. Operation, excision of left adrenal, easy operation. Oct. 4.
      Active, eating well. Weight 333 gm. At 10:48 a.m. injected 0.75 cc. of 2 per cent
      morphine sulfate intravenously ( = 45 mg. per kg.). 10:50 a.m. respirations
      imperceptible. Board-like rigidity. 11:10 a.m. respirations very shallow.
      Complete coma. 1 p.m. condition gradually improving. Oct. 5. Alert and active,
      eating well. Oct. 11. Active, eating well (15 gm. per day). Weight 335 gm.
      Operation, excision of right adrenal. Easy operation, no hemorrhage. Moderate
      fat. Oct. 18. Excellent condition, active, good appetite. Weight 321 gm. At 3:50
      p.m. injected 0.74 cc. of 1 per cent morphine sulfate intravenously ( = 23 mg.
      per kg.). 3:52 p.m. respirations imperceptible for a minute, and rat is stiff.
      3:57 p.m. voluntary movement. Oct. 19. 9 a.m. very quiet. Marked ruffling of fur.
      Not eating. 6 p.m. very quiet and dopey. Oct. 20. Found dead this morning.
      Autopsy.-Well preserved fat. Diarrhea. Thyroid rather large and red. Heart and
      lungs normal. Abdomen: both adrenals absent. No accessories seen. Stomach: five
      distinct hemorrhages into mucous membrane, one is 3 x 4 mm. Protocols 5.-Rat 24;
      white and gray, male. Sept. 27. Active. Weight 320 gm. Operation: double
      adrenalectomy. Easy operation. Sept. 29. Eating well, alert. Oct. 2. Active, ate
      12 gm. Weight 318 gm. Oct. 3. Ate 10 gm. Oct. 4. Active. Weight 311 gm. Ate 12
      gm. At 10:30 a.m. injected 0.28 cc. of 1 per cent morphine sulfate intravenously
      (= 9 mg. per kg.). Became quiet but did not stop breathing. 5 p.m. quiet and fur
      ruffled. Oct. 5, very quiet. Eyes closed most of time. Hunched up, fur ruffled.
      Drinks with eyes closed. Not eating. Oct. 6. Head between front paws most of
      time. Pilomotor reaction marked. Oct. 7. Condition about the same. Has eaten
      nothing since operation. Oct. 8. Seems slightly more active, not eating. Oct. 9.
      Ate 5 gm. of food, first since injection. Oct. 10. Very drowsy. Stools firm and
      white. Not eating. Oct. 14. Very weak. Has not eaten 10 gm. since injection. Oct.
      15. Found dead this morning. Autopsy.-Weight 240 gm. Thyroid moderate size. Heart
      in systole. Lungs normal. Abdomen: adrenals absent. No accessories seen. Left
      testis converted into a sack filled with dark red grumous material. Right testis
      atrophied. Stomach: postmortem change.

PMID- 19868810
TI  - ON THE ANTIGENIC PROPERTIES OF HEMOGLOBIN.
AB  - Sera produced by immunization with crystalline oxyhemoglobin react species
      specifically with hemoglobin solutions. Evidence is presented that in this
      reaction the hemoglobin itself is the active substance. Conversion of
      oxyhemoglobin into methemoglobin, carbon-monoxy hemoglobin, or cyanhemoglobin
      does not alter the response to the precipitating immune serum. Not only the
      hemoglobin of homologous species, but also that of other species causes
      inhibition in greater or less degree of the precipitin reaction.

PMID- 19868811
TI  - THE QUESTION OF SENSITIZATION OF JOINTS WITH NON-HEMOLYTIC STREPTOCOCCI.
AB  - It was impossible to demonstrate a condition of specific joint sensitization to
      non-hemolytic streptococci by first injecting the joints of rabbits with small
      doses of killed non-hemolytic streptococci, or with extracts of these organisms,
      and subsequently inoculating the rabbits intravenously with homologous living
      bacteria. Joints so treated were no more liable to involvement than were other
      untreated joints of the same animals.

PMID- 19868812
TI  - STUDIES ON THE ETIOLOGY OF SNUFFLES IN STOCK RABBITS : PARANASAL SINUSITIS A
      FACTOR IN THE INTERPRETATION OF EXPERIMENTAL RESULTS.
AB  - In our experience, covering a large number of rabbits, we have found that the
      condition known as snuffles falls into different types, the acute and fatal,
      symptomatic of some underlying infection such as septicemia or pneumonia; and the
      intermittent, and the chronic. The intermittent and the chronic types considered
      in this paper are those most commonly present in laboratory stocks. Our
      observations point to a widespread prevalence of the disease among rabbits kept
      under laboratory conditions. This statement might be questioned had the stock we
      examined been derived from a single source. But the animals were procured from
      dealers who obtain rabbits in New York, Pennsylvania, Ohio, and as far west as
      Michigan. The same dealers supply the stock of most of the laboratories in the
      East. Hence we believe that this disease is found generally prevalent in this
      part of the country. We have demonstrated that practically all rabbits with
      intermittent or chronic snuffles reveal old chronic inflammatory processes of the
      upper nasal passages associated with thick inspissated pus in one or more
      sinuses. Moreover, these conditions are also present in about one-tenth of
      carefully selected, supposedly normal stock rabbits and in one-fourth of a
      casually selected group, free, during long periods of observation, from any of
      the symptoms of active snuffles. The peculiar anatomy of the animal's nose which
      predisposes to the ready formation of enclosed pockets of purulent material may
      be the cause for the chronicity of upper nasal affections. When the animal's
      resistance is lowered, the long standing, inflammatory process can flare up into
      an acute exacerbation, and then show itself as typical snuffles. Various means
      can effect this: chilling the body, the intravenous injection of foreign proteins
      such as killed vaccines, or the intranasal inoculation of microorganisms of
      divers species. Bacteriological examination of the nasal secretions or sinus pus
      from animals with snuffles and those apparently free of the disease shows the
      presence in both cases of various microorganisms-Staphylococcus albus, Bacillus
      bronchisepticus, Bacillus lepisepticus, and others, in order of frequency.
      Different bacteria may be found in different sinuses in the same animal. A lack
      of recognition of these factors has led, we believe, to erroneous conclusions
      with regard to the inciting agent of the disease. Bacillus lepisepticus and
      Bacillus bronchisepticus have been declared the incitants of snuffles. Our
      experiments, in which an attempt was made to induce the disease de novo with
      these microorganisms, failed. In all cases (with a single exception) in which
      snuffles followed, there was evidence of an infection which, judging from the
      condition of the nasal passages and from the cells in the exudates or secretions,
      had existed before the inoculations were made. Furthermore, the microorganisms
      recovered from the nasal passages had as a rule no relationship to those in the
      material inoculated. We attempted also to produce snuffles by inoculating
      intranasally the unfiltered and filtered suspensions of the ground nasal mucous
      membranes from typical cases of the disease occurring in stock rabbits. These
      attempts also failed. It appears, therefore, that intermittent and chronic
      snuffles, as it attacks rabbits kept under laboratory conditions, is, as a rule,
      a sign of an underlying condition-an exacerbation of a chronic inflammatory
      process in the upper nasal passages, associated with a purulent paranasal
      sinusitis. The microorganisms recovered are to be looked upon as tending to
      maintain such conditions but we have still been unable to reproduce typical
      snuffles with them, employing supposedly normal stock rabbits for the purpose.
      One may presume that some agent, as yet undetermined, diminishes the resistance
      of the nasal mucosa, allowing different bacteria to invade and multiply there,
      thus causing disturbance. In this respect perhaps an analogous condition exists
      to that which prevails in epidemic influenza and common colds in man. It is
      obvious that further work along these lines cannot be properly carried out with
      rabbits whose antecedent history is unknown. The problem of the incitant of
      snuffles can best be studied in a breeding stock which is well controlled, one
      affording an opportunity to observe the animals from an early period of life.

PMID- 19868813
TI  - IMMUNITY STUDIES OF ROCKY MOUNTAIN SPOTTED FEVER : II. PROPHYLACTIC INOCULATION
      IN ANIMALS.
AB  - Freshly prepared mixtures of spotted fever virus and immune rabbit serum in
      neutral or superneutral proportions confer complete immunity on guinea pigs. The
      mixtures undergo a considerable loss in immunizing power when heated to 60
      degrees C. for 20 minutes, but are still capable, if used in sufficient quantity,
      of conferring a degree of immunity on the vaccinated animal such that a
      subsequent experimental infection is rendered less severe and non-fatal. Unheated
      mixtures which had been preserved in the refrigerator at 4 degrees C. for a
      period of 32 days still retained a certain degree of immunizing property. The
      virus alone, or mixed with normal rabbit serum, when allowed to die out by
      prolonged preservation at refrigerator temperature, or when killed either by
      heating at 60 degrees C. for 20 minutes or by chemicals (chloroform, ether,
      xylene) does not induce immunity in guinea pigs.

PMID- 19868814
TI  - THE INFLUENCE OF THE FACTORS OF SEX, AGE, AND METHOD OF INOCULATION UPON THE
      COURSE OF EXPERIMENTAL SYPHILIS IN THE RABBIT.
AB  - For convenience the results are summarized in tabular form. Table I shows a
      comparison of the primary reaction in the groups of female and male rabbits
      inoculated intradermally. In Table II the incidence of metastatic lesions is
      shown in the various groups of animals. In Table III are shown the character and
      date of appearance of the generalized lesions (exclusive of orchitis) in the
      various groups of animals. The results presented in Tables I, II, and III,
      together with a study of the individual protocols, permit the following general
      statements to be made relative to the effect of the factors studied upon the
      course of experimental syphilis in the rabbit. Sex.-In the group of females
      inoculated intradermally the lesions at the site of inoculation were in general
      less marked than in the group of males similarly inoculated. Moreover, they
      attained their maximum size earlier and began to recede earlier than was the case
      in the males. In none of the females was there clinical evidence of the
      production of generalized lesions, while in the corresponding group of males
      metastatic lesions of skin or bones detectible by clinical examination occurred
      in one instance, or 14.3 per cent. In both groups there was wide variation in the
      character of the initial reaction in individual rabbits and in the time required
      for it to reach its maximum size. See PDF for Structure Age.-In the five young
      males inoculated intratesticularly the disease was not greatly different from
      that observed in the older males similarly inoculated. The initial reactions were
      slightly slower in making their appearance, but the magnitude of the reaction, as
      judged by enlargement of the testicles, was somewhat greater. The percentage
      incidence of metastatic orchitis was almost the same in the two groups. The
      younger animals showed a slightly greater incidence of generalized lesions
      involving structures other than the testicles, although the difference was
      insignificant, but the lesions were smaller, fewer in number, and confined
      entirely to the skin, and there was no instance of severe generalized lesions.
      Moreover, the occurrence of metastatic lesions (skin) in the younger animals was
      definitely delayed. Method of Injection.-In the animals inoculated by the
      intratesticular route the development of the primary reaction and the incidence
      of generalized lesions involving skin and bone were much greater than in See PDF
      for Structure the animals inoculated intradermally. Thus, of the latter group
      only one, or 14.3 per cent, showed a secondary metastatic lesion (skin), while in
      the group inoculated by the testicular route the incidence of metastatic skin and
      bone lesions was as high as 71.4 per cent. The difference in the character of the
      disease exhibited by these two groups of animals inoculated in a different manner
      is quite striking. Intratesticular inoculation produced a much more violent local
      reaction and a much greater incidence of generalized lesions than did intradermal
      inoculation. Effect of Castration.-In the group of animals with unilateral
      orchitis in which the infection was allowed to run its course without any attempt
      at suppression by removal of the initial focus, metastatic lesions appeared more
      promptly and in slightly greater incidence than See PDF for Structure in the
      group of animals in which the initial local reaction was suppressed by removal of
      the focus itself through castration. The percentage differences are not very
      great, but they are constantly in favor of the first group, as is the time
      interval of appearance. This experiment is not in strict accord with similar
      experiments observed by Brown and Pearce (3) in the past, and while the reasons
      for this difference are not clear the fact may be noted that the incidence of
      generalized lesions in uncastrated animals is somewhat higher than that reported
      by these authors, also that there was a high percentage of recurrence of primary
      lesions.

PMID- 19868815
TI  - LOCAL RESISTANCE TO SPONTANEOUS MOUSE CANCER INDUCED BY X-RAYS.
AB  - Autografts from spontaneous cancers of mice when replanted into areas previously
      exposed to an erythema dose of x-rays, failed to grow in the majority of
      instances (71.4 per cent), while similar grafts inoculated into untreated areas
      grew in a large proportion of the animals (83.6 per cent). Autografts of
      spontaneous cancer, established and growing in the skin, disappeared in 76 per
      cent of animals after the tumor and surrounding tissues had been exposed to an
      erythema dose of x-rays, whereas other autografts of similar derivation that had
      been given a like dose of x-rays outside of the body and had been implanted in
      the same animals grew progressively in 96 per cent of instances. That this result
      was not due to a greater susceptibility of the cancer cells x-rayed in situ was
      shown by the fact that tumors treated in situ with x-rays and then replanted in
      an unrayed location on the same animal grew actively. Evidently the ray had done
      no direct damage to the cancer cells.

PMID- 19868816
TI  - THE ABSORPTION OF ADRENALIN.
AB  - 1. Adrenalin solution given subcutaneously is usually rapidly absorbed, probably
      by lymphatic channels. 2. The speed of this process may be influenced by the
      circulation rate. 3. The relative amounts of adrenalin at any moment unabsorbed
      at the site of inoculation, carried in the circulating fluids, and taken up by
      the reacting tissues can be calculated from figures extracted from the curve of
      the blood pressure changes. The relative rates of transference of adrenalin into
      the blood and from the circulation into the tissues can also be estimated. 4.
      When absorption takes place rapidly a large quantity of the drug comes into
      action at once and the maximum occurs early, the curve of blood pressure reaches
      a considerable height, and subsides quickly. When absorption is slow the apex
      appears later and does not reach so high a level. 5. The response to adrenalin
      bears a logarithmic relationship to the dose employed and a method of allowing
      for this is indicated.

PMID- 19868817
TI  - CONTRIBUTIONS TO THE BIOLOGY OF TISSUE CELLS : I. THE RELATION OF CELL CROWDING
      TO TISSUE GROWTH IN VITRO.
AB  - 1. A method has been described by which it is possible to scatter isolated tissue
      cells in a suitable medium. 2. Experiments were undertaken to determine whether
      minute fragments of fibroblastic culture are able to persist and multiply when
      transferred into a new culture medium. 3. Cell divisions were not observed in
      isolated cells under the conditions of the experiment. Growth took place only
      when the tissue cells were numerous and close to one another.

PMID- 19868818
TI  - STUDIES ON VARICELLA : THE SUSCEPTIBILITY OF RABBITS TO THE VIRUS OF VARICELLA.
AB  - 1. The localization of the virus of varicella in the human skin is influenced by
      irritation. This is indirect evidence that the virus is in the blood. 2. Rabbits
      are susceptible to a virus recovered from the blood of varicella patients. 3.
      Testicular emulsions containing the virus are free from ordinary aerobic and
      anaerobic bacteria, and produce lesions in the cornea, skin, and testicles of
      rabbits. 4. The virus can be transmitted indefinitely from rabbit to rabbit by
      means of testicular inoculation, and can be preserved 29 days in 50 per cent
      glycerol at a low temperature.

PMID- 19868819
TI  - EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER : V. SURVIVAL OF THE VIRUS
      IN COLLODION SACS IMPLANTED INTRAABDOMINALLY IN GUINEA PIGS.
AB  - The typhus virus contained in the blood of guinea pigs at the height of the
      experimental disease remains infective for 31 days in collodion sacs placed
      within the abdominal cavity of guinea pigs.

PMID- 19868820
TI  - INCLUSION BODIES IN EXPERIMENTAL HERPETIC INFECTION OF RABBITS.
AB  - We have thus far failed to observe any inclusion bodies in herpetic lesions which
      in our opinion may properly be interpreted as microorganisms. Concerning the
      exact nature of the granules so fully reported by others before us, we hesitate
      to commit ourselves other than to indicate certain points of resemblance to
      nuclear debris, red blood cells in the process of phagocytosis, mitochondria,
      pigment, the "methylene blue granules" of neuroglia cells, and the Russell bodies
      of plasma cells. Obviously, the fact that the individual granules in a section
      stain in the same way by Giemsa's method, or the technique of Borrel, and look
      alike is no good reason to suppose that they are of the same composition. We
      suspect that several of our methods of staining depend more upon physical forces
      than upon the actual chemical constitution of the substances which become
      colored. So that granules which stain alike may not only differ in composition
      but may also have been recruited from different sources. This fact makes
      inferential chemical analysis extremely difficult since it is next to impossible
      to superpose all our reactions upon a single granule of microscopic size.
      Consequently, if we apply one microchemical test to a group of granules, another
      test to another group, and so on, we cannot be sure that we have been dealing
      throughout with the same substance or substances. It is our belief that the
      inclusions which are so abundant in herpetic lesions do not represent a concrete
      class of granulations sui generis but that they are of variable composition and
      are derived from several sources.

PMID- 19868821
TI  - A STUDY OF THE FACTORS UNDERLYING THE FORMATION OF ALVEOLAR PORES IN PNEUMONIA.
AB  - The epithelium lining the alveolar walls is a continuous epithelium. In both
      inflammatory and mechanical congestion of the pulmonary blood vessels, it is the
      accumulation of serum behind the epithelial cells which causes them to be shed.
      The epithelium must be shed from diametrically opposite sides of an alveolar wall
      before a "pore" can be formed. In both lobar pneumonia and mechanical edema pores
      are present, but they are not normal structures.

PMID- 19868822
TI  - ROENTGEN RAY INTOXICATION : I. BACTERIAL INVASION OF THE BLOOD STREAM AS
      INFLUENCED BY X-RAY DESTRUCTION OF THE MUCOSAL EPITHELIUM OF THE SMALL INTESTINE.
AB  - The x-ray has a specific effect upon the epithelium lining the crypts and
      covering the villi of the small intestine. A suitable dose of x-ray will destroy
      this epithelium in large measure, leaving empty crypts and naked villi exposed to
      swarms of bacteria in the intestine. Subsequently one does not observe an
      overwhelming invasion of the tissues, lymph, and blood by intestinal bacteria. It
      seems obvious therefore that the intestinal epithelium is not the all important
      barrier which protects the tissues from invasion by intestinal bacteria.

PMID- 19868823
TI  - ROENTGEN RAY INTOXICATION : II. THE CUMULATIVE EFFECT OR SUMMATION OF X-RAY
      EXPOSURES GIVEN AT VARYING INTERVALS.
AB  - A single large dose of x-rays over the abdomen will cause a definite injury of
      the mucosa of the small intestine and the severity of the clinical intoxication
      seems to parallel this recognizable epithelial injury. This clinical intoxication
      lasts 4 to 6 days if the x-ray dose is sublethal. Subsequent doses of radiation
      given within this period of clinical intoxication give recognizable evidence of
      summation or a cumulative effect. Small but repeated doses of radiation given
      within a 5 or 6 day period will cause practically the same cell injury and
      clinical intoxication as will a single dose representing the sum of the small
      doses expressed in milliampere minutes. Doses of radiation given at 6 day or
      longer intervals show no evidence of summation. The reaction of this relatively
      sensitive intestinal epithelium to radiation may be similar to the reaction of
      certain deep lying tumor tissues to x-ray therapy and our experiments may give
      information of value to physicians concerned with x-ray or radium therapy.

PMID- 19868824
TI  - ROENTGEN RAY INTOXICATION : III. THE PATH OF A BEAM OF HARD RAYS IN THE LIVING
      ORGANISM.
AB  - X-rays which injure intestinal epithelium (and presumably other body or tumor
      cells) travel in straight lines from the target through the living tissues,
      forming a cone or beam of rays as controlled by impervious screens. It is
      probable that secondary radiation is formed, especially deep in the body tissues,
      but such radiation does no injury to intestinal epithelium outside of the cone or
      path of radiation. Lesions in the stomach and intestine may be confidently
      predicted from a knowledge of the size and form of the cone or beam of x-rays
      given over the abdomen. These lesions even more than skin burns do not heal and
      may in fact go on after many weeks to perforation. Even in the depths of the
      abdomen the duodenal lesions are as clean-cut as a peptic ulcer, indicating the
      lack of dispersion or scattering of the primary or secondary rays in passage
      through the living tissues. Transition from normal to necrotic mucosa rarely
      occupies more than 2 to 3 mm. and often can be observed in a single low power
      microscopic field.

PMID- 19868825
TI  - ROENTGEN RAY INTOXICATION : IV. INTESTINAL LESIONS AND ACUTE INTOXICATION
      PRODUCED BY RADIATION IN A VARIETY OF ANIMALS.
AB  - These experiments show that the common laboratory animals are about equally
      sensitive to the x-ray given over the abdomen. The clinical reaction following a
      M.L.D. is very similar and the intestinal pathology almost identical. The rat and
      guinea pig are slightly more sensitive to the x-ray than are the dog, cat, and
      rabbit. By contrast birds, frogs, and reptiles are very resistant to the x-ray
      and may tolerate two or three doses of radiation lethal for dogs. We can offer no
      convincing explanation for this fact which is discussed above. These data
      strengthen our belief in the scattered and incomplete observations on human cases
      which indicate that the human intestinal tract is likewise sensitive to
      radiation. This fact must be given careful consideration in conditions where
      abdominal or pelvic radiation is being used because such injury done to
      intestinal epithelium is always serious and in some cases irreparable.

PMID- 19868826
TI  - ELECTROCARDIOGRAPHIC EVIDENCE OF MYOCARDIAL INVOLVEMENT IN RHEUMATIC FEVER.
AB  - These observations then show that in one way or the other the heart was affected
      in 35 of 37 cases of rheumatic fever. The evidence was of three sorts; first, the
      duration of auriculoventricular conduction was increased, though not always, and
      usually not to the degree of causing heart block; second, alteration in the
      ventricular complex of the electrocardiogram affecting in certain instances the Q
      R S complex and in others either the interval between R wave and T wave, or the T
      wave itself; and third, the occurrence of numerous irregularities in cardiac
      rhythm. These signs are characteristic of cardiac involvement, but are not
      specific for rheumatic fever; that is to say, from their presence rheumatic fever
      cannot be diagnosticated; all of them express merely derangement of the heart.
      They are signs which are, however, to be taken as evidence that the heart is
      affected by the rheumatic process even though an inference cannot be drawn as to
      the nature or the permanence of the injury. This may be slight and altogether
      transient even if the sign appears to be of advanced degree. The facts brought
      forward show that it is possible during the course of the disease to know whether
      the heart is involved in the general process. When sufficient data have been
      accumulated over a sufficiently long period of time, the usefulness for prognosis
      of observations like these will become established.

PMID- 19868827
TI  - THE ROLE OF ANHYDREMIA AND THE NATURE OF THE TOXIN IN INTESTINAL OBSTRUCTION.
AB  - 1. Data are presented which show that anhydremia does not play a leading role in
      the causation of symptoms in intestinal obstruction. 2. Chemical changes in the
      blood corresponding with those noted by previous investigators were observed. 3.
      Additional data regarding the chemistry of the toxin found in the obstructed
      intestine of dogs were obtained.

PMID- 19868828
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : III. THE IMMUNITY OF A SURVIVING POPULATION.
AB  - Mice which survive a preliminary dose per os of paratyphoid-enteritidis bacilli
      are more resistant to a second dose per os of a similar epidemic mouse typhoid
      strain than are mice which have received no preliminary culture. The amount of
      this resistance is related to the pathogenicity of the preliminary strain more
      than to its antigenic similarity to the second strain. Mice which survive a
      preliminary dose per os of paratyphoid-enteritidis bacilli are more resistant to
      a lethal dose of mercury bichloride per os than are mice which have not received
      the preliminary bacterial culture. Mice which have resisted and mice which have
      recovered from a preliminary dose per os of paratyphoid-enteritidis bacilli are
      more resistant to a lethal intraperitoneal dose of an epidemic mouse typhoid
      strain than are mice which have not received the preliminary culture. Mice in
      which the preliminary dose of paratyphoid-enteritidis bacilli has induced a
      chronic infection readily succumb to a second dose of such bacilli. These
      findings indicate that the resistance mechanism of the host contains important
      non-specific factors which vary in degree with the individual mice.

PMID- 19868829
TI  - STUDIES ON VIRULENCE : II. THE INCREASE IN VIRULENCE IN VITRO OF A STRAIN OF
      PNEUMOCOCCUS.
AB  - 1. An automatic apparatus is described by which a new supply of food can be
      furnished actively growing organisms at any desired interval of time-an automatic
      transferring device. 2. A single strain of pneumococcus, Type I, Neufeld, which
      had become avirulent for mice, acquired virulence of maximal degree when grown in
      the described apparatus with skimmed milk sterilized in an Arnold sterilizer as
      the medium. Transfers were made at intervals of 2, 4, and 8 hours. It is
      difficult to determine the best interval of transfer, but the 8 hour interval
      apparently is most suitable, with the 4 and 2 hour following in preference in the
      order named. 3. Pasteurized skimmed milk from a single dairy, but obtained on
      different days, when used as medium at a 2 hour interval, varied in effect on the
      virulence of pneumococci, the results showing that the virulence might be either
      increased, decreased, or maintained. 4. Skimmed milk heated for varying lengths
      of time, 30 minutes at 17 pounds pressure, or 60 or 90 minutes at the same
      pressure, lost its suitability for maintaining virulence of a pneumococcus when
      transferred every 2 hours, the effect being in direct proportion to the length of
      time the milk was heated. 5. The H ion concentration of milk had slight effect on
      virulence. A virulent strain of pneumococcus was grown in milk adjusted to pH =
      5, 6, 7, 8, and 9, transfers being made every 2 hours. Virulence was maintained
      to a like degree on milk titrated to pH = 5, 6, and 7, but when the organism was
      grown in milk of pH = 8 and 9, virulence decreased, more rapidly at pH = 9 than
      at pH = 8. 6. A pure line practically avirulent strain of pneumococcus picked by
      the Barber method, when grown in milk at a 4 hour interval of transfer, increased
      in virulence 10 million fold; that is to say, until one diplococcus would kill a
      mouse. Prior to this study, no record has been found in which the virulence of
      any microorganism has been increased to such a degree by an in vitro method.

PMID- 19868830
TI  - STUDIES ON VIRULENCE : III. INFLUENCE OF HYDROGEN ION CONCENTRATION AND OF
      INGREDIENTS OF PLAIN BROTH ON THE VIRULENCE OF PNEUMOCOCCI.
AB  - 1. A highly virulent strain of pneumococcus, Type I, Neufeld, when grown in an
      automatic transferring device at 2 hour intervals on different lots of plain
      broth adjusted respectively to pH = 6.5, 7, 7.5, or 7.8, lost its virulence at a
      rate in direct ratio to the H ion concentration of the media-the more acid the
      media, the more rapid the decrease. 2. Growth of a virulent pneumococcus upon
      plain broth of an H ion concentration changing gradually either to the acid or
      the alkaline side of neutrality was accompanied by an initial rise in virulence
      with a subsequent fall, the change being more rapid in the alkaline than in the
      acid medium. The organism under these conditions underwent an alteration in its
      behavior toward agglutinating sera; although still specific, its agglutinability
      became much greater than that of the original organism. This change was more
      pronounced in the alkaline than in the acid medium. 3. The virulence of a
      relatively virulent culture of a pneumococcus grown on plain broth underwent
      different alterations when the organism was transferred at intervals of 1, 2, 4,
      or 8 hours. With the 1 hour interval, there occurred seemingly an immediate
      decrease in virulence, while at intervals of 2, 4, and 8 hours, there occurred
      first a rise and then a fall, the rise being greatest with the 8 hour interval of
      transfer and least with the 2 hour. 4. Meat infusion adjusted to various H ion
      concentrations-pH = 7, 7.3, and 7.7-and made with different amounts of meat
      furnished conditions which caused a decrease in virulence, the unfavorable action
      varying in inverse proportion to the concentration of the infusion. Dextrose
      added to both plain broth and to meat infusion neutralized to a marked degree the
      unfavorable action of these media. 5. The growth of pneumococci on the different
      ingredients of plain broth, with plain broth made from the same supply as a
      control, revealed the fact that peptone in 2 per cent solution maintained and
      even increased the virulence of the strain of pneumococcus studied, while meat
      infusion caused the usual decrease. The rate of decrease with plain broth was
      slower than with meat infusion, showing that the 2 per cent peptone neutralized
      to some extent the unfavorable action of the infusion.

PMID- 19868831
TI  - A REACTION PRODUCT IN INFECTIONS WITH TRYPANOSOMA LEWISI WHICH INHIBITS THE
      REPRODUCTION OF THE TRYPANOSOMES.
AB  - 1. In infections with Trypanosoma lewisi in the rat there are three
      manifestations of resistance against the parasite: (1) the retardation and final
      inhibition of reproduction of the trypanosomes by about the 10th day; (2) a
      sudden drop in the number of parasites in the blood between the 9th and 15th
      days; and (3) the total disappearance of the parasites, which terminates the
      infection and occurs from a week to several months after the first drop in
      numbers. 2. The first manifestation of resistance, vis. the retardation and final
      inhibition of reproduction, is the result of the formation of a reaction product
      in infected rats which inhibits reproduction of the trypanosomes but does not
      kill them. 3. No product similar to, or identical with this reaction product can
      be demonstrated in in vitro cultures of Trypanosoma lewisi.

PMID- 19868832
TI  - SURFACE TENSION OF SERUM : VII. SIGNIFICANCE OF THE MAXIMUM TIME-DROP OF SERUM
      SOLUTIONS.

PMID- 19868833
TI  - AN ATTEMPT TO ISOLATE A FILTER-PASSING VIRUS IN EPIDEMIC INFLUENZA.
AB  - 1. Six cases of epidemic influenza in various stages of disease were
      investigated. 2. Suspicious cultures of bodies resembling Bacterium pneumosintes
      were obtained in three cases, twice from the lung filtrates of inoculated animals
      and once from the filtrate of nasopharyngeal washings direct. 3. In these
      instances material was obtained within 36 hours of the acute onset, thus
      confirming the observations of Olitsky and Gates. 4. Macroscopic and microscopic
      findings in the lungs of inoculated animals were uniformly negative.

PMID- 19868834
TI  - BRAIN LESIONS OF THE DOMESTIC RABBIT.
AB  - Lesions of meningoencephalitis were found in 55 per cent of 372 rabbits
      comprising the laboratory stock regarded as healthy, others with snuffles or
      dying from different affections while being kept under observation, and still
      others which were employed for experimental purposes, such as tumor
      transplantation and Treponema pallidum inoculation. None was injected
      intracerebrally. The lesions consist in the main of infiltration with mononuclear
      cells occurring around the blood vessels, in the meninges, in the cortex, and
      under the ependyma of the lateral ventricles, together with particular focal
      necrotic areas in the cortex. The incidence of these histopathological changes
      varies in different series of animals; in those supposedly normal and in rabbits
      inoculated with a transplantable tumor or with Treponema pallidum material, the
      percentage of positives was from 40 to 60; in those suffering from miscellaneous
      diseases, such as pneumonia, septicemia, etc., the percentage was 70, and in
      rabbits ill with snuffles, as many as 76 per cent were affected. Marked lesions
      were observed in 47.5 per cent of the total. The histopathological picture
      observed in these rabbits corresponds to those offered by a number of
      investigators as evidence of the transmission of certain nervous diseases of man
      to this animal. The accidental cerebral lesions in the rabbit, of a wide variety,
      and of frequent occurrence, are to be regarded as existing before any
      experimental procedure is begun. Their recognition is of the utmost importance in
      the interpretation of experimental results based on the presence of similar
      changes in this animal.

PMID- 19868835
TI  - AN EXPERIMENTAL STUDY OF MITOCHONDRIAL CHANGES IN THE THYROID GLAND.

PMID- 19868836
TI  - OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION : I. EXPERIMENTAL
      CHOLELITHIASIS IN THE ABSENCE OF STASIS, INFECTION, AND GALL BLADDER INFLUENCES.
AB  - Gall stones frequently form in dogs intubated for the collection of bile under
      sterile conditions, in the absence of stasis and of gall bladder influence. The
      stones consist almost entirely of two substances-calcium carbonate and calcium
      bilirubinate-and they are remarkably uniform in character, as would follow from
      the limiting conditions of their development. They are not the result of bile
      loss, for similar ones may be recovered from the wall of glass tubes interpolated
      in ducts with intestinal connection undisturbed. The study of them has brought
      out evidence on the general problem of cholelithiasis. Some factors in their
      causation and that of gall stones as a class will be considered in succeeding
      papers.

PMID- 19868838
TI  - REVIVED ACTIVITY OF THE VIRUS OF POLIOMYELITIS.
AB  - A strain of the virus of poliomyelitis has been described which has passed
      through several stages of virulence as tested upon monkeys. The first stage
      consisted of the adaptation of the original human virus to the monkey. In this
      process high virulence was readily achieved. The adapted, virulent strain of
      virus was passed regularly through monkeys and maintained its activity for about
      3 years, when diminution became apparent. The loss of power of the virus was such
      that it may be said to have returned approximately to the level of the original
      human virus. This change constituted the second stage. The third stage is
      represented by recovery of the high virulence. This revival occurred, it seems,
      during the sojourn of the virus in glycerol and required several years for its
      consummation. It was first noticed nearly 6 years after the low level of the
      second stage became established. The potent virus of the third stage has been
      found to remain active over a period of at least 4 years while preserved in
      glycerol. What constitutes at least a superficial resemblance between the wave
      like rises and falls of the incidence of epidemic poliomyelitis and the phenomena
      of increase and decrease in virulence of the specimen of virus has been alluded
      to. The two processes differ, however, essentially in respect to the time factor,
      since the fluctuations of the epidemic wave occupy small and those of the
      virulence occupy large increments of time.

PMID- 19868837
TI  - OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION : II. ON CERTAIN SPECIAL
      NUCLEI OF DEPOSITION IN EXPERIMENTAL CHOLELITHIASIS.
AB  - A day-to-day study has been made of the sediment in the sterile liver bile of
      intubated dogs. There exists a marked tendency for calcium carbonate to be
      deposited therefrom. After hepatic or duct injury a great deal of organic debris
      of various sorts may be present in the bile, but it never causes deposition out
      of the fluid save when it accumulates in quantity on the tube wall. Particles of
      the material of which "bile thrombi" are composed may be found in the bile when
      the liver has been appropriately damaged, but these fail to act as centers of
      stone formation. On the other hand, there are to be found in the secretion after
      many sorts of hepatic injury little nuclei which undoubtedly serve in this way.
      These nuclei consist of a mixture of calcium bilirubinate and carbonate with an
      organic shadow or scaffolding. They do not occur in normal bile, but, coming down
      on special occasions, prove favorable to deposition out of the secretion
      elaborated at later periods. We have found nuclei strikingly similar in their
      relationship to stone formation, but consisting almost wholly of carbonate, in
      the sterile bile from human gall bladders which contained large calculi. Many of
      them were encountered in a free state, and others with layers of cholesterol and
      organic matter upon their surface, while others yet were recognizable deep within
      matured stones. The factors concerned in the genesis of gall stones consisting of
      calcium carbonate have been reviewed at some length in this paper and the
      preceding one. The evidence we have collected supports the view that the
      development of carbonate stones in human beings as well as in the dog may be a
      consequence, not of changes in the bile brought about by microorganisms, nor of
      the elaboration of an inflammatory exduate rich in calcium salts, but merely of
      inflammation such as leads to lessened motility of the duct system with the
      accumulation of organic debris. The fact that infection is almost the sole agent
      whereby such inflammation is set up and maintained in clinical instances had led
      too often to the conclusion that it serves as the essential agent in the process
      of calcification. The present findings taken with those described in a preceding
      paper suffice for an understanding of the immediate history of the gall stones
      which develop in intubated dogs. But the factor of individual differences, as yet
      undefined in nature, bulks large in the problem of the lithiasis, as does that of
      the local physiological safeguards against it.

PMID- 19868839
TI  - STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION : I. THE PROTECTIVE ACTION OF GELATIN
      FOR PNEUMOCOCCI IN SUSPENSION.
AB  - Experiments were undertaken with the purpose of determining the type of non
      nutrient fluid most suitable for the suspension of pneumococci with a minimum
      amount of injury. For comparative studies, dilutions in the various fluids tested
      were made from a standard suspension containing approximately 1,000 million
      pneumococci per cc. The protective properties of each solution were judged by the
      length of time viable organisms could be recovered (in culture) from a suspension
      containing 0.0000001 cc. of the standard suspension. The hydrogen ion
      concentration of the solutions, the temperature at which the suspensions were
      kept, and the culture media were carefully controlled. Furthermore, plates were
      made at the beginning of the experiment to determine the number of organisms
      present in a unit of suspension. It was found that pneumococci suspended in
      Locke's solution, 0.5 and 0.9 per cent NaCl solutions, and water, remained alive
      for only a few hours at most. Salt solution was shown to be the least suitable of
      these three; not infrequently by the time the 0.000001 cc. dilution in this fluid
      had been reached, the suspension was sterile. The addition, however, of 0.1 per
      cent gelatin to the above fluids transformed all, except 0.9 per cent NaCl, into
      highly favorable solutions. Pneumococci suspended in gelatin-water and gelatin
      Locke's solution remained alive at room temperature for 6 to 7 days; in gelatin
      salt 0.5 per cent solution, for at least 2 days. It was possible to vary the H
      ion concentration of the suspension fluids from pH 7.0 to 8.2 without any marked
      effect on the results. However, a pH of 7.4 to 8.0 appeared to be the most
      suitable. The nature of the protective action of gelatin was investigated. Series
      of plates made at frequent intervals failed to reveal any growth in suspensions
      of pneumococci containing this small concentration of gelatin. The beneficial
      effect of gelatin in the above solutions was found to lie largely in its
      protection of the pneumococci against the mechanical injury which occurs during
      the process of dilution in crystalloid solutions or water. Gelatin shows in
      addition a well marked preservative action, that is to say, it protected
      organisms against early dissolution. The nature of this preservation is
      uncertain. The presence of 0.1 per cent gelatin in 0.9 per cent NaCl failed to
      protect pneumococci against the toxic action of Na. But it was found possible to
      neutralize to a considerable degree this toxic effect of sodium by the addition
      of a small quantity (2 per cent) of a M/15 balanced phosphate mixture or sodium
      phosphate. In a gelatin-salt 0.9 per cent solution buffered with phosphate,
      pneumococci survived for 24 to 48 hours. Even in gelatin-salt, 0.5 per cent the
      presence of phosphate had a definite beneficial effect.

PMID- 19868840
TI  - STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION : II. A METHOD FOR DEMONSTRATING THE
      GROWTH-INHIBITORY AND BACTERICIDAL ACTION OF NORMAL SERUM-LEUCOCYTE MIXTURES.
AB  - Somewhat discordant results which have been reported by others who have
      investigated the property of the whole blood of resistant animals to cause
      inhibition of growth or death of pneumococci have led us to investigate this
      matter and to develop a new technique in which the conditions as they are present
      in the animal body are more nearly imitated. The observations already made have
      rendered it probable that phagocytosis plays some role in any destructive power
      for pneumococcus which whole blood possesses. We have, therefore, employed
      mixtures of serum and leucocytes in our tests, since when blood is coagulated the
      conditions become highly artificial. Furthermore, in order to imitate more nearly
      the conditions in the circulating blood the mixtures have been constantly, though
      gently, agitated. For this purpose a specially devised apparatus has been
      employed. The mixtures of serum and leucocytes have been inoculated with varying
      numbers of pneumococci in the active growth phase and after varying intervals of
      time the tubes containing the mixtures of serum, leucocytes, and bacteria have
      been opened, examined microscopically, and cultures made. Employing this
      technique it has been found that the growth of pneumococci having low virulence
      for cats is markedly inhibited in mixtures of cat serum and cat leucocytes. It
      was impossible to recover pneumococci from the tubes showing no apparent growth,
      either when the contents were transplanted into various kinds of culture media,
      or when the contents were injected into mice of a variety highly susceptible to
      pneumococcus infection. 10,000 times the number of pneumococci sufficient
      ordinarily to kill a mouse failed to do so after a 24 hour sojourn in the cat
      serum-leucocyte mixture. Mixtures of dog serum and leucocytes exert a similar
      action. The serum and leucocytes of animals susceptible to pneumococcus infection
      (rabbits and guinea pigs,) on the other hand, failed to injure pneumococci even
      in extremely small quantities. These results indicate that the blood of resistant
      animals, at least of the dog and cat, possesses destructive properties for
      pneumococci, and that this destructive power is not possessed by the blood of
      certain susceptible animals. The experiments suggest that natural immunity
      depends chiefly, if not entirely, upon this property. The leucocytes play an
      active part in this process, but whether the destruction of the pneumococci
      occurs entirely within the leucocytes or not is not determined. That the serum
      also plays a part is shown by the fact that when the serum of resistant animals
      was inactivated before being used in the serum-leucocyte mixture, the growth of
      even very small numbers of pneumococci was not prevented. Further experiments
      with cat serum and leucocytes were carried out to determine the optimum rate and
      time of agitation, the amount of serum and leucocytes required, and also the
      period of incubation necessary for the inhibition of growth and death of the
      pneumococci to occur.

PMID- 19868841
TI  - STUDIES IN AGGLUTINATION : I. THE AGGLUTINATION OF STREPTOCOCCI.
AB  - 1. The spontaneous agglutination of streptococci has been studied. 2. This
      spontaneous agglutination would seem to be caused by the presence of a bacterial
      cohesive force higher than that usually found when bacteria are suspended in salt
      solutions of the concentration commonly employed as electrolyte in specific
      agglutination reactions. 3. Many granular autoagglutinating strains of
      streptococcus may be made diffuse by growth at room temperature (17-23 degrees
      C.) and then lose their tendency to agglutinate spontaneously. 4. All factors
      that reduce cohesive force or that make the repelling force relatively greater
      than the cohesive force make for stable suspensions. 5. Methods for management of
      the specific agglutination of refractory autoagglutinating strains of
      streptococci have been presented.

PMID- 19868842
TI  - HOMOLOGOUS AND HETEROLOGOUS PROTECTION IN MICE VACCINATED WITH THE TWO TYPES OF
      MOUSE TYPHOID BACILLUS.
AB  - A saline vaccine prepared from our stock strain of M. T. II produces in mice
      definite protection against the homologous strain, and perhaps some slight cross
      protection against M. T. I also. Two vaccines prepared with our stock strain of
      M. T. I failed to produce any definite protection in mice even against the
      homologous strain, nor was any cross-protection afforded against M. T. II.

PMID- 19868843
TI  - THE OCCURRENCE OF PEROXIDE IN CULTURES OF PNEUMOCOCCUS.
AB  - 1. Conditions which favor the formation and accumulation of peroxide in broth
      cultures of pneumococcus are free access of air, and the absence of catalase,
      peroxidase, and other catalysts capable of decomposing this compound. Under these
      favorable conditions peroxide becomes demonstrable in the culture fluid during
      the logarithmic phase of growth and persists for a period of at least 6 to 12
      days. 2. In the absence of these favorable conditions the formation of peroxide
      is inhibited. In a culture with deficient oxygen exposure the accumulation of
      peroxide is delayed; when anaerobic conditions are maintained the substance is
      not formed. In the presence of active catalysts, peroxide does not accumulate in
      the medium in quantities sufficient to give a positive reaction. The accumulation
      of peroxide in pneumococcus cultures is dependent upon the balance between the
      amount produced by the microorganisms and the amount destroyed by substances in
      the medium. 3. The peroxide formed in pneumococcus cultures is unstable. It
      gradually disappears during prolonged incubation at 37 degrees C.; it is less
      stable in alkaline than in neutral or acid media. It is destroyed in culture
      filtrates exposed to the temperature of boiling water for 15 minutes, and to that
      of steam under pressure (15 pounds) for 10 minutes. 4. Peroxide formation
      occurred early in broth cultures of the seven strains of pneumococcus and of the
      six strains of non-hemolytic streptococci studied. Fifteen of twenty-three
      strains of Streptococcus haemolyticus and one of three strains of Streptococcus
      mucosus formed peroxide. In the positively reacting cultures of Streptococcus
      haemolyticus and Streptococcus mucosus the presence of peroxide was not
      demonstrable until the 3rd to 5th day of incubation. Peroxide could not be
      detected at any time during growth of the two strains of Staphylococcus aureus.

PMID- 19868844
TI  - STUDIES ON BACTERIAL NUTRITION : V. THE EFFECT OF PLANT TISSUE UPON THE GROWTH OF
      ANAEROBIC BACILLI.
AB  - 1. Certain anaerobic bacteria grow under aerobic conditions in plain broth in the
      presence of sterile unheated plant tissue. 2. Aerobic growth of anaerobic
      bacteria under the above conditions may be related to the presence of growth
      accessory substances, and to the action of oxidizing-reducing systems of plant
      tissue in the destruction of toxic peroxides of bacterial origin.

PMID- 19868845
TI  - PROTEINURIA IN NEW-BORN CALVES FOLLOWING THE FEEDING OF COLOSTRUM.
AB  - The evidence presented indicates clearly that the feeding of colostrum is
      responsible for the proteinuria. Observations on many calves killed within the 3
      first days have shown that this condition is nearly universal and that it
      disappears after the 3rd day, even when the calf is not quite normal. Urine of
      fetuses and unfed calves did not contain it. By feeding different amounts of
      colostrum, by withholding it for some hours after birth, and by giving it
      alternately with milk, the appearance of protein in the urine as to time and
      quantity was clearly a function of the colostrum fed. Serum replacing colostrum
      produced the same effect to a less pronounced degree. The permeability of the
      kidneys as determined in a routine way on healthy calves killed within the 1st
      week of life ceases after the 3rd day. In the two cases fed repeatedly with
      colostrum, proteinuria was demonstrated up to 6 days in one case. The regularity
      of its disappearance in calves normally fed indicates that more experiments are
      necessary to prove a longer period of permeability. The continued excretion of
      protein in such animals may be due to a slight lesion of the kidneys. There is
      but one reference to this subject which we have been able to find. Langstein and
      Neuberg in a study of levulose and allantoin in the urine of new-born calves
      mention the presence of albumin in six cases without, however, making any
      comments as to its origin or referring it to the ingestion of colostrum.
      According to various observers, albumin may be found in traces during the 4 first
      days in over 60 per cent of infants examined. Since the food has not been taken
      into consideration renewed observations are needed to determine if the
      relationship found in calves is also true for the human infant.

PMID- 19868846
TI  - THE RELATION BETWEEN THE INGESTION OF COLOSTRUM OR BLOOD SERUM AND THE APPEARANCE
      OF GLOBULIN AND ALBUMIN IN THE BLOOD AND URINE OF THE NEW-BORN CALF.
AB  - The coincidence of the appearance of euglobulin and pseudo-globulin I in the
      blood and urine of the new-born calf following the ingestion of colostrum and the
      absence of these proteins when milk is fed support the inference that the
      proteinuria of the new-born calf is due to the ingestion of colostrum. In this
      passage the proteins are in part unaltered. The absorption and excretion of the
      proteins of blood serum have been observed. The high protein content of the feces
      of young calves-during the first few days-is to be ascribed, in part at least, to
      ingested colostrum.

PMID- 19868847
TI  - THE EFFECT OF INORGANIC SALTS ON THE CHEMICAL CHANGES IN THE BLOOD OF THE DOG
      AFTER OBSTRUCTION OF THE DUODENUM.
AB  - The chemical changes in the blood of dogs treated with various inorganic salts
      after obstruction of the duodenum are reported. Two dogs treated with sodium
      chloride survived approximately six times as long as the average untreated
      animal, one living 22 days, the other 24 days. Ammonium chloride was found to
      produce an acidosis. The administration of potassium chloride, calcium chloride,
      and magnesium chloride did not prevent the usual rise in non-protein nitrogen and
      fall in chlorides, and the fatal outcome. Iodides seemingly hasten the toxic
      process. Sodium bromide appears to have an inhibitory action upon it, but much
      less than that of sodium chloride. Sodium sulfate, magnesium sulfate, sodium
      citrate, monosodium phosphate, and disodium phosphate failed to alter the course
      of the intoxication. Atropine and pilocarpine were without therapeutic value in
      preventing the changes characteristic of intestinal obstruction.

PMID- 19868848
TI  - EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER : VI. SKIN LESIONS IN
      EXPERIMENTAL TYPHUS FEVER OF GUINEA PIGS.
AB  - The skin of guinea pigs in which the virus of typhus fever is propagated, when
      mildly irritated in advance of the febrile reaction, shows a characteristic
      exanthem during the height of the experimental disease. More drastic methods of
      irritation, however, cause a dermatitis which obscures the rash but produce in
      the corium more marked specific histopathological changes. The exanthem may aid
      the study of the specific incitant of typhus fever in the lesions.

PMID- 19868849
TI  - GROWTH-INHIBITORY SUBSTANCES IN PNEUMOCOCCUS CULTURES.
AB  - THE KNOWN FACTORS CONCERNED IN THE AUTOINHIBITION OF GROWTH OF PNEUMOCOCCUS ARE:
      1. The accumulation of acid products of metabolism, resulting in unfavorable
      reaction changes in the medium. 2. The exhaustion of the nutritive substances of
      the medium. 3. Under certain cultural conditions the formation and accumulation
      of peroxide in the medium.

PMID- 19868850
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : I. PRODUCTION OF PEROXIDE BY
      ANAEROBIC CULTURES OF PNEUMOCOCCUS ON EXPOSURE TO AIR UNDER CONDITIONS NOT
      PERMITTING ACTIVE GROWTH.
AB  - 1. Anaerobically grown pneumococci rapidly form peroxide upon exposure to
      molecular oxygen. 2. The peroxide-forming activity of pneumococci varies with
      different strains, and with the age of the cell. 3. Peroxide production by
      pneumococcus can proceed under conditions of reaction and temperature that do not
      permit active growth and multiplication of the cell.

PMID- 19868851
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : II. THE PRODUCTION OF
      PEROXIDE BY STERILE EXTRACTS OF PNEUMOCOCCUS.
AB  - In the present paper methods have been described for the preparation of sterile
      extracts of pneumococci. These extracts may be obtained by dissolving the
      bacteria in broth cultures by means of bile, or by extraction of the cellular
      substances by repeated freezing and thawing of broth or saline suspensions of
      unwashed cells. Under special precautions these extracts may be passed through
      Berkefeld filters without loss of potency. In this procedure, as in all other
      manipulations incident to their preparation, the extracts should be protected as
      far as possible from contact with air. All extracts were proved sterile by
      cultural and animal tests. Sterile extracts of unwashed pneumococcus cells
      promptly form peroxide on exposure to air. Peroxide formation is almost as active
      in extracts aerated at 2 degrees C. as in those exposed to the air at room
      temperature. Detectable amounts of peroxide may be produced by these cell
      extracts within the reaction range of pH 5 to 9, the optimal zone lying at
      reactions less acid than pH 6. The peroxide-forming activity of the extracts is
      gradually diminished by prolonged exposure to 55 degrees C., and is completely
      destroyed by heating at 65 degrees C. for 5 minutes. Cell extracts of pneumococci
      which have been thoroughly washed prior to extraction in salt or phosphate
      solutions exhibit no peroxide-forming activity. These extracts of washed cells
      may be activated by the addition of the cell washings, yeast extract, or muscle
      infusion.

PMID- 19868852
TI  - QUANTITATIVE FACTORS IN "TEST-TUBE INFECTION.".
AB  - In the preceding experiments an attempt has been made to work out on a
      mathematical basis certain laws of "test-tube infection" with special reference
      to the relation of dosage and activity of culture to resulting growth in
      favorable and unfavorable media. It has been shown that neither lag nor dosage is
      of great importance when dealing with a highly favorable medium, but that with an
      unfavorable medium both determine very directly the outcome of the inoculation.
      Certain analogies have been drawn between these test-tube results and the
      observed phenomena of human and animal infection. If conditions are actually
      similar in the latter there is a simple explanation of several of the puzzles of
      epidemiology. It becomes intelligible why a carrier of pathogenic bacteria may
      reside in a community without producing infection of the susceptibles about him
      in spite of the fact that they actually acquire the organisms, why crowding
      results in the spread of infection, and why the introduction of unusually
      susceptible people into a community where carriers are present leads not only to
      infection of these susceptibles but to infection of the general population. The
      experiments further raise the query whether alterations in natural vegetative
      activity of bacteria as well as specific alterations in virulence are of
      importance in explaining the spread of infection. Finally, it should be said that
      the present experiments are not regarded as evidence for any hypothesis of human
      infection. They merely furnish interesting analogies. Further work with animals
      along the same lines is in progress.

PMID- 19868853
TI  - OBSERVATIONS ON BLOOD REACTION IN EXPERIMENTAL PNEUMONIA.
AB  - The correlation of the lung lesions and anemia in dogs suffering from
      experimental pneumonia induced by various organisms, with changes in the
      respiratory activity and in the acid-base relationship in blood, indicates that
      the developing acidosis, most marked in the severe cases, is due chiefly to the
      effects of an anoxic anoxemia.

PMID- 19868854
TI  - OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION : III. THE RELATION OF THE
      REACTION OF THE BILE TO EXPERIMENTAL CHOLELITHIASIS.
AB  - As previous papers from our laboratory have shown, there exists a well defined
      tendency for calcium carbonate to come out of solution in the normal liver bile
      of the dog, and for it to be deposited on certain nuclei not infrequent in the
      secretion under pathological circumstances. Gall stones that had arisen in this
      fashion were a frequent occurrence in the intubated animals we studied. The
      present paper is concerned with the reasons for the absence of such stones from
      dogs with an intact biliary tract. The solubility of calcium carbonate is known
      to be markedly affected by the reaction of the fluid in which it is contained.
      The normal liver bile, out of which it tends to precipitate, is alkaline, with an
      average pH of 8.20 but in the gall bladder where conditions might otherwise seem
      especially favorable to precipitation, the secretion undergoes a change toward
      the acid side, becoming on long sojourn there, strongly acid to litmus (pH 5.18
      to 6.00). From bile as thus altered, no carbonate precipitation takes place, even
      when it becomes greatly concentrated as in fasting animals or after obstruction
      of the common duct. Furthermore, carbonate which has precipitated out of liver
      bile on standing dissolves again in it when the fluid is rendered slightly acid
      in vitro, or, in some cases merely neutral to litmus. There are several obvious
      reasons for the absence of carbonate stones from the normal ducts under ordinary
      conditions,-notably the motility of these latter, the flushing that they undergo
      from an intermittently quickened bile stream, and the cleansing and possibly
      antagonistic action of the secretion elaborated by the duct mucosa. In the
      fasting animal, one at least of these influences is almost done away with, the
      rate of bile flow is so greatly cut down; while furthermore the calcium
      concentration of the secretion undergoes a considerable increase. But pari passu
      with these changes there occurs one in the bile reaction, a diminution in
      alkalinity so great that the pH often approximates that of the neutral point for
      litmus. That this change is not a direct consequence of the increase in calcium,
      may be inferred from the findings with stasis bile, the calcium content and
      reaction of which were observed to vary independently, if in general in the same
      direction. These adjustments within the organism, some of which may be thought to
      exhibit an element of the purposeful, when considered with the test-tube
      experiments, strongly suggest that the reaction of the bile plays a critical part
      in determining the occurrence of carbonate stones, as furthermore that their
      absence from the normal gall bladder is a consequence of the changes in the bile
      reaction there occurring. The changes come about through a functional activity of
      the bladder. This being the case, one might suppose that the failure to act would
      be followed by a formation of carbonate stones. There is sufficient evidence
      available in the literature to indicate that this happens, in rabbits at least.
      It is important to know whether changes in the bile reaction play any part in
      determining the cholelithiasis of man. To determine the matter will require a
      large material. But this much we have shown, that carbonate spheroliths not
      infrequently serve in human beings as centers in a formation of secondary stones
      of carbonate and cholesterol, as further that cholesterol precipitation out of
      human bladder bile can be induced or prevented by slightly altering the reaction
      of the fluid toward the alkaline and acid sides, respectively. The possibility
      that cholelithiasis may be a consequence of sins of omission on the part of the
      biliary channels and reservoir deserves to be considered.

PMID- 19868855
TI  - THE LIVER REQUIREMENT OF THE FASTING ORGANISM.
AB  - In rats fasted after the removal of about seven-tenths of the liver the remaining
      fragment undergoes ordinarily a marked simple hypertrophy and attains the weight
      reached through a process of simple atrophy by the entire liver of fasting
      controls. Under circumstances of exceptionally severe inanition, the hypertrophy
      may not occur, the fragment remaining unchanged or even undergoing a slight
      atrophy. But since in comparable controls the hepatic atrophy is extreme, the
      duplication in the liver weights still manifests itself. It is difficult to avoid
      the conclusion that the liver changes which take place in fasting animal are
      essentially conditioned on functional demands made upon the organ. Yet great as
      is the hepatic atrophy then occurring, this does not necessarily mean that these
      demands are much lessened during inanition. For a comparison of the liver weight
      with that of the soft body (net body weight less the weight of the ligamentous
      skeleton) brings out the fact that the organ is, relatively speaking, three
      fourths as large at extreme inanition as in the well nourished individual. Of the
      missing fourth a part may be foodstuffs on temporary deposit. And the rest is
      perhaps to be accounted for by the existence of special conditions during
      inanition which favor the vicarious assumption of a part of the usual liver work
      by the other tissues. While the findings show that the liver size is essentially
      dependent on functional demands, they do not enable one to say whether the
      special demands in question come normally to the organ by way of the portal
      stream.

PMID- 19868856
TI  - INDICATIONS OF TISSUE SPECIFICITY IN A TRANSPLANTABLE SARCOMA.
AB  - 1. A sarcoma of the mouse which has proved to be transplantable to a great
      variety of strains of mice does not furnish an exception to the theory that
      transplantability is controlled by genetic factors, since this tumor possesses
      some characteristics that are more than probably genetic. 2. The phenomenon of
      the assumption of tissue specificity on the part of the host may possibly be of
      genetic origin. 3. The evidence suggests that the gonads have some influence on
      the assumption of tissue specificity on the part of the host. 4. The growth rate
      of the transplanted tumor may possibly be correlated with the genetic
      constitution of the host.

PMID- 19868857
TI  - THE INFLUENCE OF THE ADRENAL GLANDS ON RESISTANCE : II. THE TOXIC EFFECT OF
      KILLED BACTERIA IN ADRENALECTOMIZED RATS.
AB  - 1. The resistance of rats to bacterial intoxication is greatly decreased after
      double adrenalectomy. 2. This decreased resistance is dependent upon a functional
      insufficiency of the adrenal cortex. 3. A dose of killed streptococci or
      staphylococci can be obtained that is invariably fatal to adrenalectomized rats,
      before hypertrophy of cortical accessories, but never kills control rats.

PMID- 19868858
TI  - THE EFFECT OF PILOCARPINE ON THE NUMBER OF SMALL LYMPHOCYTES IN THE CIRCULATING
      BLOOD FOLLOWING LIGATION OF THE THORACIC DUCT.
AB  - In a series of animals in which the thoracic duct had been tied it was found that
      the relative increase in the number of small lymphocytes in the circulating blood
      following the intraperitoneal administration of pilocarpine nitrate was the same
      as for the control animals. While support is brought for Harvey's view that
      pilocarpine causes a lymphocytosis through the contraction of plain muscle, on
      the other hand evidence is presented which indicates that the spleen is no more
      specialized in the production of small lymphocytes than any other portion of the
      lymphopoietic system.

PMID- 19868859
TI  - STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY. I.
AB  - In this preliminary report there are presented some of the results obtained from
      crossing mice from tumor strains with males from other sources. The comparison of
      the tumor incidence in the inbred and backcross daughters, though the numbers
      given are small, supports the theory that the tendency to develop neoplasms is
      hereditary and the frequency with which tumors appear in the first filial
      generation of such crosses, indicates that the character is dominant. Additional
      experiments involving larger numbers are in progress.

PMID- 19868860
TI  - THE PATHOGENESIS OF RHEUMATIC FEVER.
AB  - It is evident that there are two distinct types of response on the part of the
      body to the infectious agent of rheumatic fever; viz., proliferative and
      exudative. The perivascular proliferative type of lesion, resembling an
      infectious granuloma, explains the subacute and chronic character of the clinical
      symptoms in many patients with this disease. Marked exudation of serum into the
      periarticular tissues and of serum and cells into the joint cavities are
      concomitants of the acute arthritis occurring with high fever and general
      intoxication; these acute exudations disappear following the administration of
      certain drugs. But their disappearance does not mean necessarily that all lesions
      of the proliferative type have resolved. In fact, we know that these last
      mentioned lesions, when present in the subcutaneous tissues, often continue for
      months; and from analogy we may conclude that they have a similar persistent
      character in other tissues of the body invaded by the causative agent of
      rheumatic fever.

PMID- 19868861
TI  - THE EFFECT OF DIGESTIVE JUICES ON THE POTENCY OF BOTULINUS TOXIN.
AB  - Botulinus toxin resists a degree of acidity equivalent to that of the stomach
      even when exposed thereto for 24 hours at 37 degrees C. It is less resistant to
      alkali, however, as shown by the fact that in a medium of weakly alkaline
      reaction its potency is reduced to less than one-tenth in 24 hours. It is
      unaffected by peptic and tryptic digestion. Because of its instability in mildly
      alkaline solutions and resistance to acid, there is reason to believe that the
      toxin is in the main absorbed from the upper portion of the digestive tract; that
      is to say, from the stomach and upper duodenum.

PMID- 19868862
TI  - THE EFFECT OF ANESTHESIA AND OF SEDATIVES ON THE SERUM THERAPY OF EXPERIMENTAL
      BOTULISM.
AB  - When guinea pigs are fed large amounts of botulinus toxin, they develop symptoms
      of intoxication within 6 hours and die usually within 12 hours after the feeding
      of toxin. If very large amounts of toxin are introduced intraperitoneally, the
      animals may show symptoms of intoxication at the end of the 1st hour and die
      usually within 2 hours following the administration of toxin. If these animals
      are placed under anesthesia following the administration of toxin, the
      intoxication proceeds much more slowly. Anesthesia, by ether, is effective in
      this manner whether the toxin is given per os or intraperitoneally. The life of
      guinea pigs kept under ether after the administration of lethal amounts of toxin
      is prolonged by a period approximately equal to that during which the
      administration of the anesthetic is continued. When anesthesia is discontinued,
      the intoxication proceeds at its usual rate. It appears, therefore, that
      administration of ether delays the rate of intoxication but does not alter the
      toxin or the nature of the mechanism of intoxication. Anesthesia thus delays the
      progress of intoxication not only when administered immediately after the intake
      of toxin, but when administered much later after the intoxication has already
      progressed far enough to cause definite objective symptoms of poisoning. At this
      late stage of intoxication, the unsupported serum therapy of botulism in guinea
      pigs usually remains without effect. If, however, the animals are anesthetized at
      this time and kept under the influence of ether for some time, antitoxin therapy
      becomes effective. Indeed the antitoxin treatment can be delayed further for
      several hours, provided the animal is kept under anesthesia during the interval.
      Results of a similar nature were obtained with luminal sodium, nitrous oxide
      oxygen mixture, and morphine used in place of ether. In view of the fact that the
      published data indicate that botulinus antitoxin has thus far failed to give
      beneficial results in the treatment of botulism in human beings because, as it
      would seem, of the rapid progress of intoxication, any method of delaying the
      progress of intoxication to supplement the antitoxin therapy deserves
      consideration.

PMID- 19868863
TI  - EXPERIMENTS ON THE SURVIVAL OF THE FEBRILE HERPETIC AND ALLIED VIRUSES IN VITRO.
AB  - These studies fail to confirm the statements previously made that microorganisms
      of the class of the globoid bodies of poliomyelitis may be cultivated in the
      Smith-Noguchi medium from the so called virus of encephalitis lethargica. They
      show equally that the herpes virus does not multiply in this medium. The
      experiments indicate, moreover, that the medium is unfavorable to the survival of
      the virus, while ordinary broth under aerobic conditions is more favorable for
      maintaining the activity of both the encephalitic and the herpes viruses.
      Probably no multiplication of either takes place in the latter medium but merely
      a survival, and for a maximum period of 6 days in the broth itself, and 12 days
      in the fragment of brain tissue immersed in the broth. Finally, it has been shown
      that with a suitable technique the viruses can be passed from the brain of one
      rabbit to that of another through a long series without contamination with cocci
      or other common bacterial forms. Hence we regard all reports of the finding of
      ordinary bacteria in the brain of cases of epidemic or lethargic encephalitis as
      instances of mixed or secondary infection arising during life, or examples of
      postmortem invasion of the body, or of faulty technique at the autopsy.

PMID- 19868864
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : III. REDUCTION OF METHYLENE
      BLUE BY STERILE EXTRACTS OF PNEUMOCOCCUS.
AB  - 1. Sterile broth extracts of unwashed pneumococci, entirely free from living or
      intact cells, actively reduce methylene blue. 2. Sterile extracts prepared by
      extracting washed pneumococci in phosphate solution are unable by themselves to
      reduce methylene blue. Upon the addition of meat infusion or yeast extract, these
      washed cell extracts actively reduce methylene blue. 3. The system or systems in
      pneumococcus extracts responsible for methylene blue reduction are destroyed by
      exposure to temperatures practically identical with those which have been
      previously found to destroy the peroxide-forming activity of the same extracts.
      4. It is suggested that peroxide formation and methylene blue reduction by
      pneumococcus extracts are functions of the same or closely related systems, the
      particular reaction induced depending upon whether molecular oxygen or methylene
      blue serves as hydrogen acceptor or oxygen donator.

PMID- 19868865
TI  - EXPERIMENTAL OBSERVATIONS ON THE "CURE" OF SYPHILIS IN THE RABBIT WITH
      ARSPHENAMINE.
AB  - 1. The intravenous administration of six doses of arsphenamine to syphilitic
      rabbits in amounts of 10 mg. per kilo, 127 days after inoculation is sufficient
      to render the popliteal nodes of such animals incapable of transmitting the
      infection to normal animals. 2. Syphilitic rabbits that have been treated in this
      manner and whose popliteal nodes 32 to 38 days after treatment have been shown to
      be incapable of transmitting the infection to normal animals are, as far as can
      be judged by the absence of a local lesion, refractory to a second inoculation of
      active virus of the same strain, if the inoculation be made intradermally at the
      base of the ear and carried out 209 days after the first inoculation. 3.
      Untreated syphilitic rabbits are also refractory toward a second inoculation made
      in a similar manner and at a similar interval following the first inoculation. 4.
      Evidence is offered in favor of the view that the most satisfactory method of
      evaluation of antisyphilitic agents in experimental syphilis of the rabbit is
      that of lymph node transfer. 5. Evidence is offered in support of the view that
      the state of refractoriness toward a second inoculation exhibited by syphilitic
      rabbits may be explainable upon the basis of either an acquired immunity or
      persistence of a focus of living treponemata in the body.

PMID- 19868866
TI  - THE CORRELATION OF CERTAIN PHENOMENA OCCURRING DURING THE GROWTH OF PNEUMOCOCCUS.
AB  - The growth of a culture of pneumococcus was followed together with the time
      relations of some of the phenomena incident thereto. There were, roughly
      speaking, three periods of growth: first, the period of maximum rate, or
      logarithmic period; second, a brief stationary period; and third, the period of
      decline, during which actual death of individual organisms in the culture
      occurred. It has been pointed out that the usual preliminary latent period was
      avoided by the use of relatively large inoculum, obtained from a culture which
      was itself in the logarithmic period of growth. During the height of growth
      activity of the culture certain changes in the substrate became demonstrable.
      Between the 7th and 10th hours the reaction of the medium was changed by the
      production of acid and the soluble specific substance was detected. At a somewhat
      later time in the logarithmic period of the culture peroxide was demonstrable
      and, simultaneously with the appearance of this substance, the substrate acquired
      the ability to change catalase-free crystalline hemoglobin to methemoglobin.
      Moreover, changes then occurred in the cultural fluid, such that, after the
      removal of the parent organisms by filtration, it no longer supported growth when
      seeded with either the pneumococcus or staphylococcus. These changes occurred
      early in the logarithmic period of growth of the culture.

PMID- 19868867
TI  - THE INTERACTION OF TWO FRAGMENTS OF PULSATING HEART TISSUE.
AB  - Fragments of heart from the same species, when cultivated in vitro, are capable
      of uniting and pulsating synchronously. This happens not only in fragments
      derived from the same heart but with those from different individuals of the same
      species. It was not possible, on the other hand, to obtain, under the conditions
      of experiment, any physiological union of a heart fragment from a duck embryo
      with one from a chicken embryo, though both pulsated in the same medium and
      though the tissue cells of the duck were capable of growth and multiplication.
      From the experiments it is evident that cell contact is essential for the
      development of physiological identity as just described. Since such a
      physiological identity cannot be obtained through the union of a fragment of a
      duck heart and a fragment of a chicken heart, one may suppose that anastomosis
      between the cells must play a very significant role in it.

PMID- 19868868
TI  - THE DIFFERENTIATION AND KERATINIZATION OF EPITHELIUM IN VITRO.
AB  - The organization, or, according to Drew, differentiation, of epithelial cells
      grown in vitro is not due to a specific influence of the associated connective
      tissue. It occurs in all old pure cultures of epithelium, when the tissue
      fragment becomes thick and suffers from lack of oxygen and nourishment. Under the
      same circumstances, keratinization occurs in cultures of epithelium.

PMID- 19868869
TI  - EXPERIMENTAL STUDIES WITH A SPIRAL ORGANISM FOUND IN A WILD RAT.
AB  - 1. Two cases of rat-bite fever with a typical fever course and a maculopapular
      exanthem came under my observation in Mexico. 2. A spiral organism
      morphologically identical with one known in Japan as the causative agent of
      Sodoku was found in a Mus decumanus caught in Mexico City. 3. The organism was
      found to be pathogenic for white rats and guinea pigs, the infection being fatal
      for guinea pigs. 4. The bite of an infected guinea pig led in one of two
      instances to infection and death of the animal bitten. 5. The microscopical
      findings in the guinea pigs infected with this microorganism closely resemble in
      many respects the findings in Blake's case and in Kaneko and Okuda's first case,
      the only ones of human rat-bite fever which have been closely studied at post
      mortem. 6. Eye lesions were found in all the infected guinea pigs and the spiral
      organisms were demonstrated in the discharge from the eyes and also within the
      cornea. 7. Similar eye lesions were found in most of the infected rats and the
      secretion from the eyes of one of them was demonstrated to be infectious for
      guinea pigs. 8. The eye lesions constitute an evident source for the spiral
      organisms transmitted by biting, and not improbably the only one. My experiments
      may give an explanation for the transmission of some other spirochetal diseases
      besides rat-bite fever. Cases of Weil's diseases are reported to be caused by the
      bite of a rat and it is noteworthy that eye lesions occur in spirochaetosis
      icterohaemorrhagica (Manson).

PMID- 19868870
TI  - THE RATE OF HEALING OF WOUNDS.

PMID- 19868871
TI  - THE REVERSE SELECTIVE BACTERIOSTATIC ACTION OF ACID FUCHSIN.
AB  - 1. The reverse selective action attributed to acid fuchsin can be explained on
      the basis of spore resistance. This action does not apply to the vegetative cells
      of Gram-positive spore bearers. It cannot be extended to include the Gram
      negative spore bearers. 2. The selective action of acid fuchsin is that of an
      ordinary weak disinfectant and is not comparable to the selective action of the
      triphenylmethane dyes. 3. A lack of parallelism between the bactericidal and
      bacteriostatic action of acid fuchsin can be explained on the basis of spore
      resistance and it does not exist when spores are excluded. 4. Acid fuchsin is a
      weaker disinfectant than basic fuchsin for both Gram-negative and Gram-positive
      bacteria. The process of sulfonation by which acid fuchsin is made from basic
      fuchsin results in a reduction in the bactericidal action of the dye for Gram
      negative and Gram-positive bacteria. 5. The most significant fact in the action
      of the dyes on bacteria is the toxic effect of the triphenylmethane dyes on Gram
      positive spore-bearing organisms.

PMID- 19868872
TI  - AN IMMUNIZING STRAIN OF THE VIRUS OF POLIOMYELITIS.
AB  - In this communication we have described a strain of the virus of poliomyelitis
      derived from a rapidly fatal human case, which exhibits mild degrees of infective
      power and marked degrees of protective effect for the monkey. While Macacus
      rhesus displays perceptible differences in suceptibility to the attenuated virus,
      nearly all individuals respond to the inoculation and none succumbs to the
      infection induced. As compared with previously described examples of experimental
      poliomyelitis, the modified disease described in this paper is distinguished by
      its relatively benign nature and its tendency to end in recovery rather than, as
      with the earlier observed instances, in death.

PMID- 19868873
TI  - EXPERIMENTS ON ANAPHYLAXIS TO AZOPROTEINS.
AB  - From the experiments which have been reported, it follows that animals sensitized
      with one azoprotein react not only to the antigen used for the sensitization, but
      also to other azoproteins made up from the same simple azo-compounds and another
      protein. Although the specificity of the reaction has not yet been tested with
      various azo-components, its actual existence can reasonably be assumed on the
      basis of the phenomena observed in precipitation reactions. The sensitization is
      brought about with less facility than sensitization against the usual antigens
      and the effects are not uniform. Still, after sufficient treatment, 40 per cent
      of the animals succumbed with typical anaphylactic symptoms, mostly within a
      short time while 16 per cent showed severe symptoms. The experiments show that it
      is possible to make animals hypersensitive against a simple chemical group like
      para-arsanilic acid, and from this point of view connection would seem to be
      established with the phenomena of drug allergy in human beings. There is an
      essential difference, however, in that the sensitized animals did not react on
      injections of simple compounds such as para-amino-phenyl-arsanilic acid and
      phenyl-4-arsonic-acid-azo-tyrosine uncombined with protein. It remains to be
      determined whether under changed conditions positive results in this direction
      can be obtained. For this purpose it seems advisable to make experiments with
      isolated organs, according to the method of Schultz and Dale. While the simple
      substances failed to elicit direct reactions, they protected (as was foreseen by
      Doerr) against a subsequent injection of the active antigen. Similar compounds
      not containing the arsanilic acid group were considerably less active. The
      phenomenon is comparable to the inhibition of precipitin reactions already
      described. Considering the protection as a condition of antianaphylaxis, one
      would suppose that the simple substances mentioned are fixed by the cells in
      which the anaphylactic reaction takes place. It may be concluded that: 1. Animals
      can be sensitized through injections of one azoprotein-protein combined with
      diazotized para-arsanilic acid-against another compound containing the same azo
      component but a different protein. 2. Injections of related simple compounds, as
      for instance para-arsanilic acid and phenyl-4-arsonic-acid-azo-tyrosine did not
      cause shock in the sensitized animals under the conditions of the present
      experiments. 3. The simple compounds mentioned and other related substances as
      well protect against the anaphylactic action of azoprotein, by inducing a state
      of antianaphylaxis.

PMID- 19868874
TI  - THE EFFECT OF X-RAY ON THE SKIN OF VITALLY STAINED WHITE MICE : ESTABLISHMENT OF
      AN X-RAY UNIT FOR THE SKIN OF THE MOUSE.
AB  - 1. The time interval between radiation and the occurrence of epilation is shorter
      in mice injected with trypan blue than in normal animals. 2. An x-ray unit
      defined as that causing total spontaneous epilation on the skin of the mouse is
      suggested. It corresponds to four to five human erythema doses.

PMID- 19868875
TI  - PENETRATION OF NORMAL MUCOUS MEMBRANES OF THE RABBIT BY TREPONEMA PALLIDUM AND
      THE INFLUENCE OF THIS MODE OF INFECTION UPON THE COURSE OF THE DISEASE.
AB  - Experiments were carried out with three strains of Treponema pallidum to
      determine whether infection could be produced by applying an emulsion, rich in
      spirochetes, to normal mucous membranes of rabbits and whether an infection
      produced in this manner differed in any respect from one produced by other
      methods of inoculation. It was found that a simple instillation of a spirochete
      emulsion into the conjunctival sac or the sheath was all that was necessary to
      obtain an infection. Still, the infection produced in this manner differed from
      that produced by intracutaneous or testicular inoculations in that it tended to
      pursue a mild or asymptomatic course and frequently without the development of a
      characteristic chancre. It is pointed out that these experiments may have a
      bearing on problems pertaining to obscure and atypical cases of human syphilis as
      well as the more immediate question of the infectivity of Treponema pallidum.

PMID- 19868876
TI  - THE FATE OF ANTIGEN (PROTEIN) IN AN ANIMAL IMMUNIZED AGAINST IT.
AB  - When proteins such as horse serum or crystalline egg albumin which have been
      selected because they produce the phenomena of immunity are introduced into a
      normal animal they diffuse widely in the tissue, enter the blood stream, and are
      disseminated throughout the body. The same substances introduced into an immune
      animal are fixed at the site of entry and are not found in the blood. When
      protein is injected into the skin of an immune animal acute inflammation (Arthus
      phenomenon) occurs at the site of injection and brings about destruction of the
      foreign substance.

PMID- 19868877
TI  - STUDIES ON THE RESPIRATORY MECHANISM IN LOBAR PNEUMONIA : A STUDY OF LUNG VOLUME
      IN RELATION TO THE CLINICAL COURSE OF THE DISEASE.
AB  - 1. The functional residual air (defined as the lung volume at the end of normal
      expiration) has been determined in a series of normal individuals and in ten
      patients with lobar pneumonia at different stages of the disease. 2. The rate,
      depth, and minute volume of respirations were measured in the same individuals by
      a graphic method. 3. When appreciable cyanosis was present the oxygen content and
      capacity of the arterial blood were determined. 4. A constant relationship has
      been found to exist between the persistence and disappearance of symptoms (fever,
      accelerated heart rate, rapid and shallow breathing, cyanosis) and fluctuations
      of the functional residual air. When these symptoms persisted the functional
      residual air decreased; during their disappearance the volume of the functional
      residual air rose towards normal. The rise was detected soon after the crisis. 5.
      A close parallelism has been observed also between alterations in radiographic
      shadow, physical signs, and the volume of the functional residual air. The lung
      volume, measured at normal expiration, is diminished during the persistence of
      pathological signs in the lungs, and returns to normal as the pathological signs
      disappear. The average time required, in cases which recovered, for the
      functional residual air to become constant was 11 to 12 days, counting from the
      onset of the disease.

PMID- 19868878
TI  - THE RELATION OF BLOOD PRESSURE TO THE AMOUNT OF RENAL TISSUE.
AB  - The removal or destruction of about 70 per cent of the kidney tissue in rabbits
      does not produce hypertension even when prolonged renal insufficiency results.

PMID- 19868879
TI  - SURFACE TENSION OF SERUM : VIII. FURTHER EVIDENCE INDICATING THE EXISTENCE OF A
      SUPERFICIAL POLARIZED LAYER OF MOLECULES AT CERTAIN DILUTIONS.
AB  - The assumption has been made in preceding papers that, at a given concentration
      of 1:10,000, in the vessels used in our experiments, a monomolecular oriented
      layer was formed. Such a layer might be supposed to prevent the free escape of
      water molecules from the surface into the air, at least to a certain extent. In
      order to check this assumption, the rate of evaporation of solutions of serum at
      different concentrations was measured. It was found that, under the conditions of
      the experiments, in a progression of dilutions from 10(-1) to 10(-6), the slowest
      evaporation took place at a concentration of 1:10,000. In a few cases (less than
      20 per cent), evaporation was slower at a different concentration, but always
      within the same range (between 10(-3) and 10(-5)), not far from 10(-4).

PMID- 19868880
TI  - THE INFLUENCE OF RESISTANCE ON THE CHARACTER OF DISEASE IN EXPERIMENTAL
      RESPIRATORY INFECTION.
AB  - An organism of the Pasteurella group (Pasteurella avicida) has been shown to
      possess considerable pathogenicity for rabbits when injected into the trachea. 1
      cc. of bouillon containing 1/100 cc. of a 24 hour bouillon culture introduced by
      means of a curved metal tube passed through the larynx gives rise to a rapidly
      fatal septicemia in which the lungs are not particularly involved. Rabbits may be
      made completely resistant to this intratracheal infection by means of
      intratracheal, intraperitoneal, or subcutaneous injections of killed cultures.
      Vaccination and subsequent injection of living culture beneath the skin resulted
      in extensive abscess formation about the site of inoculation. Vaccines sprayed on
      the mucous membranes of the nose and throat failed to raise appreciably the
      resistance against subsequent intratracheal injection. Rabbits whose resistance
      has been stimulated within narrow limits by a small dose of vaccine beneath the
      skin become more resistant to the experimental respiratory infection. The
      character of the disease is changed from a rapidly fatal septicemia without lung
      involvement to a more prolonged pneumonia. The blood remains sterile for varying
      periods. Consolidations of the more dependent lobes occur with considerable
      regularity. In two instances a characteristic empyema developed in the course of
      the experiments.

PMID- 19868881
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : IV. OXIDATION OF HEMOTOXIN
      IN STERILE EXTRACTS OF PNEUMOCOCCUS.
AB  - In the present work on oxidation and reduction by sterile extracts of
      pneumococcus, the preparations employed contain among other constituents, a
      hemolytic substance the properties of which have been described by Cole (1, 2) in
      his studies on pneumococcus hemotoxin. Pneumococcus extracts prepared by the
      methods described are actively hemolytic, 0.005 cc. of extract causing complete
      lysis of 2.5 cc. of a 1 per cent suspension of red cells from rabbit blood. This
      hemolytic property of pneumococcus extracts is destroyed by 10 minutes exposure
      to 55 degrees C. When pneumotoxin-containing extracts are protected from the
      action of molecular oxygen, their hemolytic activity remains unimpaired for
      considerable periods of time. In the presence of air, on the other hand, the
      stability of the hemolytic substance depends upon whether the particular type of
      extract contains a "complete" or "incomplete" oxidation-reduction system. Sterile
      broth extracts of unwashed pneumococci are reactive with molecular oxygen, and as
      a result of this union peroxide is formed whenever these extracts are exposed to
      air. The hemolytic activity of "complete" extracts of this type is rapidly
      decreased and finally destroyed in the presence of molecular oxygen. On the other
      hand, the "incomplete" type of extract prepared by saline extraction of washed
      pneumococci may be exposed to air with little or no loss of hemolytic power. This
      "incomplete" washed cell extract, unless reactivated, does not undergo
      autoxidation in the presence of air; under these circumstances peroxide is not
      formed and the hemolytic activity of this type of extract is not impaired by
      exposure to air. The stability of the hemolytic agent in the "incomplete" type of
      extract is evidence that this substance is itself not reactive with or affected
      by molecular oxygen, even in the presence of the cell enzymes. The destruction of
      the same hemolytic substance in extracts capable of undergoing autoxidation may
      be ascribed to the action of some peroxide formed by the union of molecular
      oxygen with easily oxidized or autoxidizable substances of the extract. It is now
      known that a peroxide, having the reactions of hydrogen peroxide, accumulates in
      sterile pneumococcus extracts during oxidation. It has been shown in the present
      study that the addition of preformed hydrogen peroxide destroys the hemolytic
      activity of pneumococcus extracts, although higher concentrations were required
      than were detected in oxidized extracts themselves. These facts and the known
      action of superoxides in analogous types of reaction make it seem not unlikely
      that the active agent in the destruction of pneumotoxin in oxidized cell extracts
      may be a peroxide; either hydrogen peroxide or some higher organic peroxide
      formed during autoxidation of the extract.

PMID- 19868882
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : V. THE DESTRUCTION OF
      OXYHEMOGLOBIN BY STERILE EXTRACTS OF PNEUMOCOCCUS.
AB  - 1. Sterile broth extracts of unwashed pneumococci actively destroy hemoglobin to
      methemoglobin and lower degradation products. 2. Sterile saline extracts of
      washed pneumococci do not by themselves form methemoglobin; extracts of this type
      may be completed or activated by the addition of certain complementary substances
      such as meat infusion and yeast extract. 3. The hemoglobin-destroying activity of
      pneumococcus extract is lost by exposure to 65 degrees C. for 10 minutes. 4. The
      properties of an extract upon which these blood changes depend are related to
      other known oxidation-reduction functions of the same extract. 5. Oxyhemoglobin
      is converted to methemoglobin only by cell extracts in the reduced form;
      completely oxidized extracts are inactive in the presence of blood. The action of
      hydrogen peroxide and the influence of blood catalase on these reactions are
      discussed. 6. During the reaction between oxyhemoglobin and pneumococcus extract
      oxygen is consumed. 7. The mechanism of methemoglobin formation by pneumococcus
      is interpreted as an oxidation process in which deoxygenation of oxyhemoglobin
      and peroxide formation occur as intermediary reactions. The active agent of the
      oxidation of hemoglobin is considered to be a peroxide of bacterial origin.

PMID- 19868883
TI  - FURTHER OBSERVATIONS ON THE PHENOMENA ENCOUNTERED IN ATTEMPTING TO TRANSMIT
      VARICELLA TO RABBITS.
AB  - 1. The intradermal method of inoculating Virus III, a hitherto unknown filterable
      virus producing lesions in rabbits, gives more reliable results than those
      obtained by smearing the virus on the scarified skin. 2. Virus III, heated 10
      minutes at 55 degrees C., will not produce visible reactions in the skin of
      rabbits. 3. Virus III passes through Berkefeld N and V filters. 4. The data
      obtained so far indicate that the best method of preserving Virus III in an
      active state is to filter the testicular emulsions containing the virus, add
      glycerol to the filtrate up to 40 per cent of the total volume, seal with
      vaseline, and store on ice. 5. Viable Virus III produces a definite immunity in
      rabbits which persists for at least 6 months. The immunity follows intradermal,
      intratesticular, intravenous, intracerebral, or intranasal inoculations of the
      virus. 6. A single intradermal injection of Virus III, which has been killed by
      heat, will not produce a demonstrable immunity in rabbits. 7. No passive immunity
      to Virus III could be demonstrated in rabbits which had received intravenous
      injections of 5 to 10 cc. of immune rabbit serum 24 hours previously. 8. Immune
      rabbit serum neutralizes Virus III either in vitro, or locally in a rabbit's skin
      when the immune serum and the virus are injected into the same part of the skin
      at or about the same time. 9. Three strains of the virus under investigation are
      immunologically identical. 10. Virus III and vaccine virus are immunologically
      distinct. 11. Virus III and the virus of symptomatic herpes are immunologically
      distinct. 12. No passive immunity to Virus III could be demonstrated in rabbits
      which had received intravenous injections of 5 to 10 cc. of serum or whole blood
      from patients convalescent from varicella. 13. Sera from two normal adults and
      from fourteen patients convalescent from varicella did not neutralize Virus III
      in vitro. 14. Rabbits could not be actively immunized against Virus III by
      injections of whole blood, vesicle fluid, or nasal washings from patients with
      varicella. 15. Four of twenty sera collected from stock rabbits of different
      ages, 20 per cent, neutralized Virus III in vitro. The animals whose sera
      neutralized Virus III failed to show a reaction at the site of intradermal
      inoculations with the same virus. About 15 per cent of 200 young stock rabbits
      (1,800 gm.) used in routine transfers were found to be refractory to Virus III,
      as evidenced by a failure to react to intradermal inoculations of the virus. 16.
      No susceptibility to Virus III was observed in guinea pigs, mice, or monkeys. 17.
      A volunteer who had never suffered from varicella experienced no general reaction
      and only a mild local one following an intradermal inoculation of Virus III. A
      volunteer who had had chicken-pox in childhood experienced a moderate general
      action, viz., fever, headache, backache, and general malaise, and also a moderate
      local reaction, viz., redness, swelling, tenderness, and pain, following an
      intradermal inoculation of Virus III. 18. The study of the immunological
      reactions has failed to bring any evidence that the virus under investigation
      bears an etiologic relationship to varicella.

PMID- 19868884
TI  - THE TRANSMISSION AND TREATMENT OF INFECTIOUS OPHTHALMIA OF CATTLE.
AB  - The experiments in which transmission of the disease was attempted by flies
      hardly parallel the observations within the herd. It is not unusual to observe
      large numbers of flies feeding on the exudate. Slight disturbances may interrupt
      feeding and cause the flies to disperse and within a short period alight about
      the eyes of other cows. The experiments, however, bring out the fact that the
      bacterium will not remain viable for even a few minutes in the digestive tract of
      the fly. Its life on the external surfaces of the fly is extremely short and in
      our observations has not exceeded 3 hours. The latter fact strengthens the
      opinion that in the main the infection is not dust-borne since the bacterium soon
      dies when not in contact with the eye. Two other points are of considerable
      significance. The ability of the organism to maintain itself on the eye for
      considerable periods after the acute symptoms have subsided may explain the
      reappearance of cases during the warmer months. The organism can exist in the eye
      throughout the winter and with the warm weather flies may transmit it to other
      susceptible individuals and thus a nucleus of an epidemic may be established. The
      presence of the organism in the nasal passages in the incubation stage and early
      in the disease in two of our experimental animals affords an explanation for the
      appearance of the disease in sporadic cases in the colder months. It is assumed
      that nasal exudate as a fine spray may be forcibly expelled and directly reach
      the eyeball of a normal individual. It has been shown that small quantities of
      culture sprayed on the cornea are capable of giving rise to the characteristic
      disease. The irregularity of the elimination of the organism through the nostril
      may be explained by the effect of inflammation on the tear duct. In experimental
      cases a small quantity of bouillon containing the culture was dropped or sprayed
      on the cornea. Doubtless the bacilli are deposited on the mucosa of the tear
      duct. Here they may multiply and set up an inflammation and thus gain access to
      the nasal passage. To what degree the virus is spread by the forcible expulsion
      of nasal secretion containing lacrimal fluid cannot be determined. The
      elimination of the bacilli from the nasal passage in our experimental
      inoculations leads us to believe that in the main the phenomenon is associated
      with early infections. The examination of the nasal passages of a large number of
      well established cases with negative findings tends to corroborate this view. Of
      interest to those concerned with the treatment of animal diseases is the
      readiness with which the inflammation subsides when treated with 1:40 zinc
      sulfate.

PMID- 19868885
TI  - THE VIABILITY OF HEMOLYTIC STREPTOCOCCUS IN CERTAIN SOLUTIONS CONTAINING GELATIN.
AB  - 1. The findings of Robertson, Sia, and Woo with regard to the preservative action
      of 0.1 per cent gelatin in suspending fluids for the pneumococcus have been
      confirmed for the streptococcus. 2. In gelatin-citrate, gelatin-Locke's, and
      gelatin-"20:1" solutions, the streptococcus will live for 3 days or longer at
      room temperature and for 12 hours or longer at incubator temperature in dilutions
      as high as 100 cocci per cc. 3. The gelatin in 0.1 per cent concentration
      maintains life at a fairly constant numerical level for from 15 to 24 hours.
      These fluids may therefore be used for certain quantitative biologic tests. 4. In
      slightly higher concentrations of gelatin, there is actual growth which suggests
      that even in 0.1 per cent concentrations the gelatin has a nutrient action. 5.
      There is also evidence that gelatin affords some protection against the
      mechanical injury of the dilution process. 6. The toxic action of unbalanced
      salts, the possible lytic action of water, and the autolytic action of the
      organisms themselves are all delayed by the presence of gelatin, but eventually
      these actions take place in the same manner that has been described before by
      many observers and as here observed for solutions without gelatin. 7. The life of
      streptococci is maintained in these gelatin solutions through a relatively wide
      zone of hydrogen ion concentration.

PMID- 19868886
TI  - AN HISTOLOGICAL STUDY OF THE CENTRAL NERVOUS SYSTEM IN EXPERIMENTAL BOTULINUS
      POISONING.

PMID- 19868887
TI  - THE EPIDEMIOLOGY OF A RABBIT RESPIRATORY INFECTION : I. INTRODUCTION.

PMID- 19868888
TI  - THE EPIDEMIOLOGY OF A RABBIT RESPIRATORY INFECTION : II. CLINICAL, PATHOLOGICAL,
      AND BACTERIOLOGICAL STUDY OF SNUFFLES.
AB  - 100 adult rabbits taken at random from The Rockefeller Institute animal house
      were examined clinically, anatomically, and bacteriologically for evidence of
      respiratory infection. 58 of these rabbits proved to have snuffles; 42 were free
      of the disease. Bacterium lepisepticum was the predominating organism in the
      nasal flora of 55 of the 58 rabbits showing snuffles. This organism was also
      cultured from the nasal passages of eight normal rabbits. Bacillus
      bronchisepticus was associated with Bacterium lepisepticum in the nasal flora of
      eight rabbits with snuffles. It was also cultured from the nares of twenty-two
      normal rabbits. Fifteen normal rabbits showed neither Bacterium lepisepticum nor
      Bacillus bronchisepticus.

PMID- 19868889
TI  - THE EPIDEMIOLOGY OF A RABBIT RESPIRATORY INFECTION : III. NASAL FLORA OF
      LABORATORY RABBITS.
AB  - THE BACTERIA CONSTITUTING THE NASAL FLORA OF RABBITS AT THE ROCKEFELLER INSTITUTE
      MAY BE ENUMERATED AS FOLLOWS IN THE ORDER OF THEIR FREQUENCY: (1) Micrococcus
      catarrhalis group, 80 per cent; (2) Bacterium lepisepticum, 70 per cent; (3) Gram
      negative cocci which ferment dextrose, lactose, saccharose, maltose, and mannite,
      but not salicin and Bacillus bronchisepticus, 40 per cent; (4) Staphylococci,
      streptococci, and various intestinal bacilli which probably are localized at the
      external nares, 10 per cent. Bacterium lepisepticum is the predominating organism
      in the nasal passages of the rabbits affected with snuffles.

PMID- 19868890
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : IV. THE EFFECT OF SELECTIVE BREEDING ON HOST RESISTANCE.
AB  - If mice surviving a lethal dose of mouse typhoid bacilli are inbred consecutively
      for a number of generations, the resulting offspring become progressively more
      resistant to mouse typhoid infection and to mercury bichloride intoxication than
      similar control mice not so selected.

PMID- 19868891
TI  - THE CONCENTRATION OF THE PLASMA PROTEINS IN NEPHRITIS.
AB  - In nephrosclerosis (Volhard and Fahr classification of nephritis) there was no
      decrease in the plasma proteins. With heart failure the ratio of albumin to
      globulin fell from the normal 1.7 +/- 0.3 to about 1. There is a sharp difference
      between the two types of glomerulonephritis in the effect on plasma proteins. In
      the vascular-interstitial type the effect was the same as in nephrosclerosis.
      There was no decrease in the plasma proteins until shortly before death. In the
      glomerulotubular or nephrotic type, active or recently active, the total plasma
      proteins were less than 5 gm. per 100 cc. This decrease from the normal 5.5 to
      7.5 occurred whether edema was present or absent. The decrease affected chiefly
      the albumin, the globulin being usually diminished but little, and sometimes
      slightly increased. Consequently the ratio of albumin to globulin was reduced to
      less than 1, and occasionally to 0.6. In nephrosis similar changes were found in
      the total protein concentration but in severe cases the decrease in albumin was
      greater than in nephrotic glomerulonephritis while the globulin was either very
      slightly reduced or was increased. The albumin : globulin ratio was therefore
      lower than in nephrotic glomerulonephritis, ranging down to 0.26. With the
      disappearance of edema there was usually an increase in the plasma protein
      concentration, but this was not invariable, and concentrations of 4.5 per cent or
      less were compatible with the persistent absence of edema. The ratio of albumin
      to globulin showed an irregular tendency to rise. Whenever the total
      concentration was less than 4 per cent there was some edema present, but it was
      sometimes slight in amount. With recovery in acute cases, and remission with
      decrease of proteinuria in chronic cases, normal concentrations were regained.
      The albumin : globulin ratio remained low in some instances for a longer period
      on account of an absolute increase in globulin concentration. In "functional
      proteinuria" no change in plasma proteins was found. Low plasma protein
      concentrations were always associated with considerable losses of protein in the
      urine, but these losses did not provide an explanation for all our observations.
      A disturbance in the production of the plasma proteins appears probable.

PMID- 19868892
TI  - CHANGES IN THE VOLUME OF PLASMA AND ABSOLUTE AMOUNT OF PLASMA PROTEINS IN
      NEPHRITIS.
AB  - 1. We have not observed gross increases in plasma volume in glomerulonephritis,
      nephrosis, or nephrosclerosis, even when the concentration of plasma proteins was
      much below normal. Our results indicate the probability that "hydremic plethora"
      does not occur. 2. The low protein concentration frequently observed in the
      plasma in nephritis is not due to increased plasma volume but to a decrease of
      the total amount of plasma protein in the body. 3. Changes in plasma volume
      showed no constant relationship to changes in edema.

PMID- 19868893
TI  - FAT METABOLISM IN NEPHRITIS.
AB  - Determinations of the plasma lipoids and of the respiratory quotient and total
      metabolism (Tissot method) have been performed with nephritics and normal
      subjects before and after they ingested fat in the proportion of 1 gm. per kilo
      body weight. After fat ingestion a greater increase of fatty acids and lecithin
      was noted in the plasma of nephritics with initially high blood lipoids than in
      the plasma of normal subjects or of nephritics without constant lipemia. In
      cholesterol no differences were found. The nephritic patients with constant
      lipemia were able to burn fat as efficiently as normal individuals. The
      accumulation of fat in their blood may be due to a disturbance in the mechanism
      for transferring lipoids from the blood to the tissue depots.

PMID- 19868894
TI  - THE BEHAVIOR OF THE LEUCOCYTES DURING COINCIDENT REGENERATION AND THYROID-INDUCED
      METAMORPHOSIS IN THE FROG LARVA, WITH A CONSIDERATION OF GROWTH FACTORS.
AB  - 1. Coincident progressive and regressive changes are induced in the tail of the
      frog larva by simultaneous thyroid administration and removal of a portion of the
      tail. The rate of growth of the regenerating tail is greatest in animals not
      treated with thyroid, next greatest in animals treated with thyroid 2 days after
      tail removal, somewhat less in animals treated with thyroid simultaneously with
      tail removal, and least in those treated with thyroid 2 days before removal of
      the tail. 2. The leucocytes chiefly concerned are neutrophilic granulocytes,
      lymphocytes, hemoblasts, and lymphoid phagocytes (monocytes, macrophages). The
      neutrophils further tissue lysis, the lymphoid phagocytes remove tissue debris.
      The lymphocytes are apparently not numerous enough to exert any important growth
      promoting influence. The hemoblasts represent merely a part of the general
      reaction to thyroid treatment. Eosinophils are absent except for a few that
      appear in the late stages. Basophils of mesenchymal origin are present in the
      later stages of thyroid-treated animals. These appear to differentiate further
      into eosinophils. 3. The rate and amount of growth are correlated directly with
      the degree of crowding of cells, and inversely with the degree of vascularity.
      The greatest crowding and least vascularity occur in animals not treated with
      thyroid, somewhat less crowding and greater vascularity in those treated with
      thyroid 2 days after tail removal, still less crowding and somewhat greater
      vascularity in those treated with thyroid at the time of tail removal, and
      finally, least crowding and greatest vascularity occur in animals treated with
      thyroid 2 days before tail removal. These results support the views of Burrows
      (4) upon the mechanism of growth stimulation of cells.

PMID- 19868895
TI  - THE EPIDEMIOLOGY OF A RABBIT RESPIRATORY INFECTION : IV. SUSCEPTIBILITY OF
      RABBITS TO SPONTANEOUS SNUFFLES.
AB  - The onset of spontaneous snuffles in rabbits at The Rockefeller Institute is
      preceded by the appearance in the nasal passages of Bacterium lepisepticum. The
      active stages of snuffles infection are associated with the presence in these
      passages of large numbers of this bacterium. Spontaneous recovery from snuffles
      is associated with a diminution in number or a disappearance of these bacteria
      from the nasal passages. Various experimental procedures reduce the resistance of
      rabbits to spontaneous snuffles.

PMID- 19868896
TI  - THE EPIDEMIOLOGY OF A RABBIT RESPIRATORY INFECTION : V. EXPERIMENTAL SNUFFLES.
AB  - Rabbits were bred at The Rockefeller Institute with special relation to
      protection from exposure to Bacterium lepisepticum. These healthy rabbits were
      then submitted to intranasal instillation of a given dose of cultures of
      Bacterium lepisepticum. The results of the inoculation were various according to
      the natural degree of resistance of the individual animals. The following graded
      effects could be distinguished: Some of the animals became (1) short time
      carriers of Bacterium lepisepticum; others (2) long time carriers of the same
      organism; some developed (3) local nasal infection (snuffles) of short duration;
      others (4) local nasal infection (snuffles) of long duration; while yet others
      had (5) snuffles, followed by pneumonia and signs of general infection after a
      few weeks; and finally there were instances of (6) local nasal discharge attended
      by general infection and pneumonia after a few days. The effects produced in any
      given healthy stock depend also upon the degree of virulence of Bacterium
      lepisepticum of which great differences exist among the same and different
      strains.

PMID- 19868897
TI  - SURFACE TENSION OF SERUM : IX. TIME-DROP AND SMALLPOX VACCINATION.

PMID- 19868898
TI  - DIET AND TISSUE GROWTH : I. THE REGENERATION OF LIVER TISSUE ON VARIOUS ADEQUATE
      DIETS.
AB  - 1. The toxicity of chloroform varies according to the diets used in these
      experiments in the following order of decreasing susceptibility of the animals:
      high fat > standard > high carbohydrate > high protein diets. 2. On the high fat
      and high carbohydrate diets there may be a more or less marked proliferation of
      the endothelium and the connective tissue stroma in the necrotic area producing
      in some instances scars resembling the picture of an early cirrhosis. 3. On the
      diets studied, standard, high carbohydrate, high protein, and high fat, the most
      active and rapid repair is observed on the standard balanced diet. On the high
      fat diet the reparative process is definitely delayed in comparison with the
      others. There are only slight differences between the high carbohydrate and high
      protein diets which suggest but do not conclusively show a more rapid repair with
      the latter diet.

PMID- 19868899
TI  - SURFACE TENSION OF SERUM : X. ON THE THICKNESS OF THE MONOMOLECULAR LAYER OF
      SERUM.
AB  - An attempt was made to apply the assumption that a monolayer of serum exists at a
      certain dilution, in order to calculate the thickness of this layer or, that is
      to say, the mean value of one of the dimensions of the molecules of the serum
      proteins. The criterion taken for the existence of such a monolayer was the
      existence at a given concentration (1/11,000 for rabbit serum) of a maximum drop
      in the surface tension of serum solutions kept in watch-glasses. A series of
      preliminary experiments showed: 1. That the maximum drop in 2 hours took place,
      for the material used, at a concentration of 1/11,000, and that it always
      corresponded to an absolute minimum value of the surface tension of the solution,
      this minimum being quite sharp and well defined. 2. That adsorption took place on
      the glass as well as on the free surface of the liquid, and that apparently the
      same part of the molecule, in both cases, was drawn toward the water. 3. That the
      specific gravity of the anhydrous proteins of the rabbit serum studied was 1.275,
      whence it followed, on the basis of 6.51 per cent protein content, that the mean
      thickness of the protein molecules was 35.4 x 10(-8) cm. The same method applied
      to crystalline egg albumin, pH 6.8, in water, gave 52.8 x 10(-8) cm. for the
      probable molecular length.

PMID- 19868900
TI  - STUDIES ON THE TOTAL BILE : VI. THE INFLUENCE OF DIET UPON THE OUTPUT OF
      CHOLESTEROL IN THE BILE.
AB  - The development of a method for the collection of total bile from dogs in a
      sterile state and uninfluenced by the gall bladder, day after day for weeks, has
      rendered possible an accurate study of the influence of diet upon the cholesterol
      output of the secretion. When a diet rich in cholesterol is given the amount of
      the substance in the bile greatly increases. Not only this but the concentration
      per cc. is, in almost every instance, greater. An increase in the total food
      intake, by the addition to the ordinary ration of a bone mash diet containing
      only a slight additional amount of cholesterol (200 mg.) produces a similar,
      though lesser, increase. In the fasting dog, the cholesterol yield is greatly cut
      down. The increase in the cholesterol after food rich in the substance does not
      depend on the cholagogue action of this latter, though it is true that the
      concentration of cholesterol in the bile usually increases with the bile volume.
      Though fasting cuts down the cholesterol of bile, the concentration of the
      substance per cc. is greatly increased. On an ordinary diet the yield of it
      fluctuates abruptly and considerably from day to day. In general the rule holds
      that an animal eating largely puts out not only much more bile but much more
      cholesterol. The relation between bile quantity and cholesterol yield is anything
      but a fixed one, however. The cholesterol yield of the bile does not parallel
      that of bilirubin. The pigment output from day to day remains relatively constant
      as compared with that of cholesterol.

PMID- 19868901
TI  - FLAGELLAR AGGLUTININS.
AB  - 1. Certain bacilli within one strain may lose their flagella and become non
      motile. 2. The change in serological behavior associated with the change in
      motility indicates that the flagella possess an individual antigenic property. 3.
      Flagella can be separated from the bodies of the bacilli. 4. A strictly flagellar
      antiserum can be produced by the injection of a flagellar suspension. 5. This
      direct production of a strictly flagellar antiserum is proof of the existence in
      flagella of a separate specific antigen.

PMID- 19868902
TI  - THE COEXISTENCE OF PROTOZOAN-LIKE PARASITES AND MENINGOENCEPHALITIS IN MICE.
AB  - A small proportion of laboratory mice, which appear to be normal, are in reality
      suffering from an obscure disease characterized by the presence of marked
      meningoencephalitic lesions which are often accompanied by protozoan-like
      parasites. Both the lesions and the parasites closely resemble others previously
      reported in rabbits, which likewise fail to reveal themselves by pronounced
      clinical symptoms. In the absence of direct experimental evidence it is suggested
      either that one species of parasite is capable of producing the lesions in both
      animals, or else that we have to do with two kinds of parasites which are closely
      related and, in the stages thus far observed, are indistinguishable one from the
      other.

PMID- 19868903
TI  - THE EFFECTS OF THE INTRATRACHEAL ADMINISTRATION OF FOREIGN SERUM.
AB  - It has been possible to sensitize guinea pigs by the intratracheal administration
      of small amounts of horse or cow serum. The degree of sensitiveness is comparable
      to that obtained when the same doses of serum are injected into the peritoneal
      cavity. Nevertheless, relatively small amounts of foreign protein are slowly
      absorbed through the lining membranes of the lower respiratory tract. In
      sensitive animals it has not been possible to produce shock by intratracheal
      injection of amounts of serum which injected into the peritoneal cavity of other
      animals of the same series sensitized in the same manner always produced shock.
      Considerably larger doses administered intratracheally may give rise to
      anaphylactic symptoms. It is possible that the force necessary to inject the
      larger amounts of serum may have led to injury and more rapid absorption.

PMID- 19868904
TI  - THE PERMEABILITY OF THE LINING OF THE LOWER RESPIRATORY TRACT FOR ANTIBODIES.
AB  - The experimental results indicate that the walls of the lower respiratory tract
      are relatively as impermeable for antibodies as they are for serum proteins. The
      kind of serum employed does not influence this fact. Antibodies contained in
      homologous (rabbit) serum failed to enter the blood stream when injected into the
      trachea in greater concentration than those contained in heterologous (guinea pig
      and cow) sera. That a little serum and its contained substances are absorbed
      after intratracheal injection has been shown both by the experiments dealing with
      sensitization and anaphylaxis previously reported and by the experiments recorded
      in this paper. Besredka's assertion that the laryngotracheal method is an
      efficient one for the administration of serum in the treatment of disease has not
      been borne out by the experimental evidence here presented. From the results one
      would conclude that it is one of the least efficient routes for administration.
      In contrast to the relative impermeability for proteins of the mucous membranes
      of the lower respiratory tract is the relative permeability of the endothelium of
      the peritoneal cavity. Antibody is there absorbed readily, whether it be in
      heterologous or in homologous serum. The indications are that a considerable
      portion of the antibody injected into the peritoneal cavity reaches the blood
      stream in 2 or 3 hours.

PMID- 19868905
TI  - CAUSE OF IMMEDIATE DEATH BY LARGE DOSES OF BOTULINUS TOXIN.
AB  - Parenteral introduction of amounts of the culture filtrate of Bacillus botulinus
      greatly in excess of the minimum lethal dose has been observed to cause the
      practically immediate death of mice. This result is due to the presence in the
      filtrates of a chemical poison possessing properties distinct from those of the
      contained botulinus toxin which itself acts only after a well defined period of
      incubation. This chemical poison is not neutralized by botulinus antitoxin; it is
      effective only when large amounts of the culture filtrate are given; it is
      thermostable, not being destroyed when heated in the autoclave in a sealed tube,
      though when it is heated in an open container its toxicity diminishes with a
      coincidental volatilization of basic material. The volatile substance can be
      identified as ammonia. Death resulting from the injection of comparatively large
      amounts of ammonium salts (0.1 gm.) is easily distinguished from that due to
      botulism, both through the character of the symptoms and the absence of an
      incubation period. However, when the amount of toxic salts injected is smaller
      (0.01 gm.), the symptoms of poisoning are not so characteristic and death may be
      delayed long enough to suggest a period of incubation similar to that observed in
      botulism (Table IV). This circumstance is of importance in connection with the
      examination of partly decomposed food products in which the presence of botulinus
      toxin is suspected. As a rule such suspected material is injected in massive
      doses (0.5 to 1 cc.) in mice. It is conceivable that such spoiled foods may be
      contaminated with common putrefactive bacteria yielding ammonia during their
      growth and thus may cause death of the test animals. If in such tests mice
      passively protected by the preliminary injection of an excess of antitoxin be
      used in addition to normal animals, the chances of an error in the interpretation
      of the results will be materially reduced, though not ruled out. Unfortunately
      for such a procedure, botulinus antitoxin is not readily available, while
      furthermore, recent findings indicate that it may not always be effective owing
      to the existence of a group of toxin-producing bacteria very similar to Bacillus
      botulinus, but not homologous immunologically with either of the known types of
      the latter. The test of thermostability of the toxic constituents of suspected
      food may conceivably help to determine the true nature of the poison.

PMID- 19868906
TI  - ON THE SPECIFICITY OF AGGLUTININS AND PRECIPITINS.
AB  - The results of the partial saturation of precipitins with antigens related in
      derivation to the homologous one give no conclusive evidence of the regular
      existence in a single immune serum of multiple antibodies which act specifically
      on various chemical groups of the antigenic proteins. It seems possible to
      explain at least a part of the facts by the assumption that a single antibody
      will react to different degrees with several similar substances. By the partial
      absorption of hemagglutinins with heterologous blood, specific fractions were
      obtained. By such means one may readily differentiate the blood of related
      species, even when precipitins show but little difference. The peculiarities in
      specificity manifested by precipitinogens and agglutinogens suggest an essential
      difference in the chemical structures which determine the specificity of the two
      kinds of antigens.

PMID- 19868907
TI  - LEAD STUDIES : III. THE EFFECTS OF LEAD ON RED BLOOD CELLS. PART 1. CHANGES IN
      HEMOLYSIS.
AB  - It appears, from the investigations in other laboratories, that the anemia
      observed in cases of lead poisoning is due to destruction of blood rather than to
      diminished production of blood. The method of poisoning cells in vitro with lead
      was adopted in order to study this phenomenon, and distinct effects were thereby
      obtained, even when only 0.001 mg. of lead is added to approximately 5 billion
      washed red corpuscles. In order to obtain optimum results the usual dosage
      employed was ten times this or 0.01 mg. per 5 billion cells. The following
      changes were observed in cells so treated. 1. Such a marked increase in the
      resistance to hypotonic salt solution develops that complete hemolysis does not
      occur until the cells are exposed to a saline solution of 0.05 per cent.
      Untreated cells are completely hemolyzed in 0.25 or 0.225 per cent saline. 2.
      This reaction is quantitative and varies with the concentration of lead used.
      Under the conditions of our experiments this phenomenon seems to be unique. The
      effects of arsenic are very slight in comparison. 3. While from this reaction it
      may be concluded that lead increases cellular resistance, it also appears that it
      shortens the life of blood cells. This may be demonstrated by the much more rapid
      appearance of hemolysis than normal when the cells are merely allowed to stand in
      Ringer solution of any dilution. 4. In rabbits with acute lead poisoning these
      same phenomena may be noted in vivo. 5. Both phenomena may be changed in vitro by
      varying the time and temperature of the reaction and the concentration of lead,
      as Fici has already pointed out. 6. If normal cells stand in Ringer solution for
      6 hours something diffuses into the solution which largely reduces the action of
      lead. After repeated washing these cells react with lead in the usual manner. 7.
      Small amounts of serum react with lead and eliminate its effects. Red blood
      cells, treated with a mixture of lead and blood serum, show normal hemolysis in
      hypotonic salt solution. 8. When lead is added to whole blood the only evidence
      of this neutralization is a marked decrease in the intensity of the reaction.
      This is probably explained by the fact that since both serum and cells are
      present together, the lead reacts with both simultaneously. This in turn explains
      how the reaction may occur in vivo. 9. The change in hemolysis does not appear in
      the blood of all species of animals. In the species in which it does occur,
      anemia and stippling of the red cells also tend to develop readily during lead
      intoxication. 10. In vitro, cells which have been exposed to lead are far more
      fragile than normal blood cells. Slight trauma causes them to hemolyze. In vivo
      this is probably an important causal factor in the increased destruction of blood
      and in the anemia of acute lead poisoning. 11. The serum of a rabbit which has
      been immunized to human blood, causes more rapid and complete hemolysis in cells
      treated with lead than in the control cells. No satisfactory explanation for this
      has been found.

PMID- 19868908
TI  - LEAD STUDIES : III. THE EFFECTS OF LEAD ON RED BLOOD CELLS. PART 2. SURFACE
      PHENOMENA AND THEIR PHYSIOLOGICAL EXPLANATION.
AB  - The physiological changes following the reaction of lead upon red blood cells are
      numerous and show the marked effects of a change in the cell surface. In
      experiments here reported 0.01 to 0.05 mg. of lead acting upon 5 billion red
      cells caused such marked variations from normal as: 1. Partial loss of the normal
      stickiness of red corpuscles, which is demonstrated by their falling from a clean
      glass surface. 2. Loss of the agglutination reaction which normally follows
      mixture with serum of a different isoagglutinating group. 3. Decrease in volume
      even in isotonic solutions. 4. Loss of normal elasticity and, therefore, reduced
      changes in volume upon exposure to marked variations in osmotic tension. 5.
      Increase in resistance to large changes in external osmotic pressure because of
      this inelasticity, and therefore decreased hemolysis in hypotonic salt solution
      (Part 1). 6. Increase in the speed of disintegration in spite of this increased
      resistance to external osmotic pressure. "Leaded" cells break up more readily
      upon standing than do normal cells, and are easily fractured by rotation or
      shaking (Part 1). All these phenomena seem to be associated largely with surface
      changes in the corpuscles. Evidence is cited that there is no chemical reaction
      between lead and hemoglobin. The gas exchange is identical in normal and "leaded"
      cells. The function of the interior of the red cells, therefore, appears to be
      unaffected by lead. The effects of lead upon red blood cells are thus manifested
      by shrinkage, inability to expand, increased brittleness, and loss of the normal
      consistency which makes their surface sticky. After exposure to lead, red blood
      corpuscles are more like hard inelastic brittle rubber balls, than like the soft,
      elastic, resilient cells characteristic of normal blood.

PMID- 19868909
TI  - LEAD STUDIES : III. THE EFFECTS OF LEAD ON RED BLOOD CELLS. PART 3. A CHEMICAL
      EXPLANATION OF THE REACTION OF LEAD WITH RED BLOOD CELLS.
AB  - These three papers have developed the following facts, which suffice to explain
      completely the anemia of lead poisoning. In vitro, the exposure to a very small
      amount of lead greatly changes the surface of the red blood cells. Their
      permeability to water is so altered that they shrink and are incapable of
      swelling as much as normal cells. With this is associated a marked increase in
      the resistance to different osmotic surroundings-demonstrated by far less
      hemolysis than normal in salt solution of very low concentrations. The "leaded"
      cells, however, are relatively short lived, and hemolyze readily as the result of
      slight trauma. These observations can also be demonstrated in vivo as experiments
      with rabbits with acute lead poisoning show. In addition to these effects on
      permeability, lead alters the physical properties of red blood cells so that they
      lose their normal stickiness and are no longer agglutinated by the sera of
      different isoagglutinating groups. All these changes are evidence of an effect on
      the surface of the cell; the interior of the cell does not undergo disturbances;
      at least, the physiological properties of the hemoglobin remain normal. The
      chemical reaction which causes these physical changes in the cell is a
      precipitation of insoluble lead phosphate and a formation of acid. This causes
      the "leaded" red blood cell to change from an elastic distensible sac, to one
      which is contracted, relatively inelastic and brittle. In such condition the cell
      can poorly withstand the trauma involved in circulation of the blood, and this
      lack of resistance probably explains the marked destruction of peripheral blood
      in lead poisoning.

PMID- 19868910
TI  - DIET AND TISSUE GROWTH : II. THE REGENERATION OF LIVER TISSUE DURING NUTRITION ON
      INADEQUATE DIETS AND FASTING.
AB  - THE RELATIVE TOXICITY OF CHLOROFORM GIVEN SUBCUTANEOUSLY TO RATS FED ON TWO DIETS
      DEFICIENT IN RESPECT TO THEIR NITROGENOUS COMPONENTS, THE SOLE SOURCES OF PROTEIN
      IN WHICH WERE, RESPECTIVELY, GLIADIN AND GELATIN AND TO RATS WITHOUT FOOD, IS AS
      FOLLOWS: gelatin diet > fasting > gliadin diet. The rate of regeneration of liver
      cells after chloroform poisoning in rats fed a diet in which gliadin is the only
      protein is about as rapid as that in animals fed a diet containing casein as the
      source of nitrogen. The rate of regeneration on a food containing its nitrogen as
      gelatin and also during fasting is definitely slower than that in animals fed the
      gliadin food. The results of these experiments indicate that the requirement for
      the essential amino acids for growth of individual organs of the body is less
      than that for correlated growth of the whole body.

PMID- 19868911
TI  - SOME CULTURAL CHARACTERS OF BACILLUS ABORTUS (BANG) WITH SPECIAL REFERENCE TO
      CO(2) REQUIREMENTS.
AB  - The relative absence of saprophytism in freshly isolated strains of Bacillus
      abortus is conveniently measured by inoculating a series of agar tubes with.
      successive dilutions of culture and sealing the tubes. The appearance of films of
      growth is delayed from 3 to 17 days and suppressed with the increase in the
      dilutions. As many as 100,000 bacteria per sq. cm. of agar surface are
      suppressed. When the confined air contains CO(2) in a concentration as low as
      (1/4) per cent and up to 10 per cent, the inhibition and suppression do not
      occur. Concentrations down to 0.1 per cent are still capable, even though in a
      slightly retarded manner, of bringing high dilutions into growth. In all cases
      the resulting growth was remarkably vigorous when compared with that in sealed
      tubes.

PMID- 19868912
TI  - A COMPARATIVE METHOD FOR TESTING THE ENZYMES OF LIVING HEMOLYTIC STREPTOCOCCI :
      I. LIPASE.
AB  - 1. A method is presented for the quantitative comparison under various conditions
      of the activity of the lipolytic enzyme of the hemolytic steptococcus. The speed
      of acid production as shown in the color change from pH 8.0 to 7.2, when the
      living streptococcus is suspended in association with ethyl butyrate, is
      considered to be indicative of the amount of ferment elaborated by the organism.
      2. The lipolytic action is a function of living, actively growing organisms such
      as are present in 4 to 8 hour cultures. 3. The speed of the lipolytic action is
      approximately in linear proportion to the concentration of the organisms. 4. The
      lipolytic action is most rapid at 37.5 degrees C., slower at 50 degrees , and
      absent at 62 degrees . 5. The organisms are partially destroyed and the lipolytic
      action is markedly delayed by previous heating to 55 degrees C. for 10 minutes.
      Both the organisms and the lipolytic activity are completely destroyed by
      continued contact with this temperature for 30 minutes. 6. Increasing the
      virulence of the organism for rabbits by repeated animal passage does not
      increase the lipolytic action. 7. The predilection of the hemolytic streptococcus
      for the subcutaneous fat in local streptococcus infection associated with
      extensive superficial gangrene cannot be explained on the basis of an increase of
      lipolytic ferment in the organisms recovered from these cases over that of
      heterologous strains of streptococci.

PMID- 19868913
TI  - STUDIES ON THE BIOLOGY OF STREPTOCOCCUS : III. AGGLUTINATION AND ABSORPTION OF
      AGGLUTININ WITH STREPTOCOCCUS SCARLATINAE.
AB  - 1. Strains of hemolytic streptococci from cases of scarlet fever occurring in New
      York, San Francisco, Chicago, Baltimore, and Copenhagen, Denmark, all
      interagglutinate with immune sera prepared with these strains. 2. Sera prepared
      with these strains do not agglutinate pyogenic streptococci or strains isolated
      from cases of septic sore throat. 3. The strains obtained from the throats of
      patients from an epidemic of scarlet fever and the strain from the milk
      responsible for this epidemic fall into the scarlatinal group according to these
      agglutination tests. 4. Absorption tests can be carried out with these strains
      and sera under proper conditions. 5. A group of hemolytic streptococci
      biologically distinct from streptococci from other sources than scarlet fever is
      constantly associated with scarlatina. They constitute a group of closely related
      streptococci which may be identified by agglutination tests.

PMID- 19868914
TI  - THE INHIBITORY EFFECT OF ACRIDINE ON THE SPOROGONY OF A COCCIDIUM (EIMERIA
      STIEDAE).
AB  - The development or ripening of the oocyst of the coccidium of the rabbit is
      prevented by acridine hydrochloride provided that the cysts are exposed to the
      action of the chemical before development has started. After sporoblasts are
      formed acridine does not prevent further development. Many other substances, some
      of them known to be active against certain protozoan parasites, have no influence
      on the ripening of the oocysts of the coccidium.

PMID- 19868915
TI  - METHEMOGLOBIN FORMATION BY STERILE CULTURE FILTRATES OF PNEUMOCOCCUS.
AB  - 1. Sterile filtrates of aerobic cultures of pneumococcus which contain hydrogen
      peroxide are capable of converting catalase-free solutions of crystalline
      oxyhemoglobin into methemoglobin. This action is dependent upon the hydrogen
      peroxide in the filtrates and occurs only in the absence of blood catalase. 2. In
      catalase-containing solutions of hemoglobin from laked corpuscles, the actual
      methemoglobin-forming system of Pneumococcus involves a labile constituent of the
      bacterial cell. This intracellular substance is itself susceptible to oxidizing
      agents and may be rendered inactive, if exposed to peroxide or similar substances
      previous to its introduction into oxyhemoglobin solutions. The activity of this
      function in the case of sterile filtrates of pneumococcus cultures depends,
      therefore, upon the liberation of cell constituents into the medium and upon the
      protection of these cellular substances from the oxidizing agents which are
      formed when pneumococcus cultures are freely exposed to air. When these cultural
      conditions are fulfilled sterile culture filtrates of Pneumococcus convert
      oxyhemoglobin into methemoglobin independent of the presence of blood catalase.

PMID- 19868916
TI  - THE LESIONS IN RABBITS EXPERIMENTALLY INFECTED BY A VIRUS ENCOUNTERED IN THE
      ATTEMPTED TRANSMISSION OF VARICELLA.
AB  - The pathological changes produced by the virus under investigation are similar to
      those deemed characteristic of a certain well known group of filterable viruses.

PMID- 19868917
TI  - PARTIAL OCCLUSION OF THE PULMONARY AORTA AND INFERIOR VENA CAVA WITH THE METALLIC
      BAND. OBSERVATIONS ON CHANGES IN THE VESSEL WALL AND IN THE HEART.
AB  - In dogs a constricting metallic band does not affect the integrity of the wall of
      the vena cava, whereas it leads to a rapid death of the wall of the aorta, and,
      as evidenced by a single instance studied, to a much slower death of the
      pulmonary artery. In the instance, just mentioned, constriction of the common
      pulmonary artery by an aluminum band for a period of 2(1/2) years led to a right
      ventricular hypertrophy.

PMID- 19868918
TI  - PARTIAL OCCLUSION OF THE AORTA WITH SILK SUTURES, AND COMPLETE OCCLUSION WITH
      FASCIAL PLUGS. THE EFFECT OF LIGATURES ON THE ARTERIAL WALL.
AB  - 1. Partial occlusion of the aorta of dogs may be produced by Halsted mattress
      sutures of silk. This occlusion persists. 2. A method of completely occluding the
      aorta of dogs by means of anchoring fascial plugs in the lumen is described. 3.
      The vessel wall below and at the site of an occluding fascial plug undergoes
      marked atrophy. 4. Ligatures used for ligating or plicating large arteries cause
      death of the arterial wall. The same is true for encircling metallic bands. 5.
      Catgut is dangerous to use for the ligation of large arteries, since it may give
      way before the necrosed vessel wall becomes completely substituted by fibrous
      tissue.

PMID- 19868919
TI  - THE SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS : SECOND PAPER.
AB  - 1. The method for the concentration and purification of the soluble specific
      substance of Pneumococcus has been improved. 2. Highly purified specific
      substance of Type II pneumococcus of polysaccharide nature is shown to be
      recovered essentially unchanged after precipitation by immune serum, by uranyl
      nitrate, by basic lead acetate, or by safranine. 3. Marked chemical differences
      are shown to exist between the specific substances of Type II and Type III
      pneumococcus, although both react as polysaccharides. 4. The weight of evidence
      is considered to be in favor of the view that the specific substances of
      Pneumococcus Types II and III are actually polysaccharide derivatives. 5. The
      immunological significance of the foregoing view is discussed.

PMID- 19868920
TI  - STUDIES ON THE TWORT-D'HERELLE PHENOMENON.
AB  - 1. The experiments here reported were carried out with a lytic principle isolated
      from the feces of normal rabbits. 2. It seems that bacteriophage is constantly
      present in the feces of caged laboratory rabbits. 3. A lytic filtrate active for
      Strain Shiga 73 (in a dilution of 1:1,000,000) and for the typhoid bacillus (in a
      dilution of 1:1,000), after twenty successive passages with Shiga bacillus was
      active, for its homologous strain, in a dilution of about 1:10,000,000,000 but no
      longer possessed any lytic activity for the typhoid strain. The same filtrate,
      after twenty successive passages with typhoid bacillus, was similarly active in a
      dilution of 1:10,000,000,000 for the typhoid strain but was only feebly active
      for the Shiga strain. 4. The passage of the lytic principle through collodion
      membranes was never observed. 5. No appreciable diminution in the activity of the
      filtrates was observed after exposure to cholesterol or lecithin. Killed
      bacterial suspensions, however, were found to exert a considerable neutralizing
      effect on the active principle. 6. Formol titrations of lysed cultures lead to
      the conclusion that the bacteriolysis caused by the bacteriophage is not a true
      proteolysis but rather a simple plasmolysis of the bacterial cell and not a
      splitting effect of the protein molecule. 7. We have never obtained active
      filtrates with the leucocytes of immune animals by the method of Lisbonne,
      Boulet, and Carrere (14). 8. It would appear, from the experiments, that the
      immunization of rabbits with the lytic principle results in the disappearance of
      the bacteriophage from their intestines. 9. All the sera from rabbits immunized
      with antityphoid or antiShiga filtrates agglutinated respectively the typhoid or
      Shiga bacilli. 10. Similarly, these sera fixed complement strongly in the
      presence of the homologous antigen. Five or six times the amount of serum was
      required to fix complement in the presence of heterologous antigen. 11. All of
      the immune sera were found to be more or less antilytic. In no case was a
      strictly specific antilysin obtained.

PMID- 19868921
TI  - THE INFLUENCE OF THE SUPRARENAL GLAND ON THE THYMUS : I. REGENERATION OF THE
      THYMUS FOLLOWING DOUBLE SUPRARENALECTOMY IN THE RAT.
AB  - Experimental evidence has been presented showing that the thymus gland of the rat
      enlarges rapidly in those animals surviving double suprarenalectomy. The
      enlargement has been observed to follow bilateral ablation with such constancy
      that it may be said to occur in all rats which survive double suprarenalectomy in
      good condition for from 3 to 5 weeks. The thymus enlarges even though the animal
      loses some weight after operation. Our data, though inconclusive, would seem to
      indicate a sex difference, the secondary hyperplasia of the thymus being more
      marked in the female than in the male. This difference, we believe, may shed some
      light on the mechanism of thymus enlargement following double suprarenalectomy.
      In the rat there is a definite sex difference in the weight of the suprarenals
      (20), the glands being much larger in the female than in the male. This weight
      difference becomes greater as the rat grows, and it appears at an early period of
      life; indeed, it is obvious at about 35 days of age, in spite of the fact that
      sexual maturity is seldom attained before 60 to 90 days. This difference in the
      suprarenals is independent of pregnancy. It is highly probable that the
      suprarenal glands stand in closer relation to the sex organs of the females than
      in the male, and that removal of these glands disrupts the sex interrelationships
      between gonads, suprarenals, and thymus, this disturbance being more definitely
      expressed in the female than in the male. The great majority of the rats were
      operated on when they were between 6 and 7 months of age; that is, after thymus
      involution would normally have set in. Thymuses examined when they had reached
      their largest size resembled both grossly and microscopically the growing
      thymuses of much younger animals, the only evidence of previous involutionary
      change being the presence of thickening of the vessels. We assume, therefore,
      from indirect, but statistical data, that regeneration of the involuted thymus
      must have taken place. The regeneration following bilateral ablation describes a
      curve which reaches its height between the 3rd and 5th weeks after operation.
      After the height of enlargement is attained, there is a gradual decline in the
      size of the gland, but involutionary changes may be retarded for months.
      Pregnancy prior to suprarenalectomy does not prevent thymus regeneration
      following this operation. Thymic enlargement does not ordinarily take place
      following a unilateral ablation. Severe chronic infections may sometimes bring
      about such a pronounced pathological involution of the thymus that the
      hyperplasia may be prevented. There can as yet be only speculation as to the
      mechanism involved in the regeneration of the thymus which follows
      suprarenalectomy. This secondary thymic hyperplasia may be one manifestation of
      the generalized lymphoid hyperplasia that follows sublethal but sufficient
      suprarenal injury, and which is characterized by the appearance of prominent
      lymphoid foci in the various organs, particularly in the thyroid, a generalized
      hyperplasia of the lymph nodes and bone marrow, and the appearance of a
      lymphocytosis in the blood. The evidence at present available would suggest that
      both the thymic and general lymphoid hyperplasia may be effected through the
      gonads and parasex tissues and that the thymus especially regenerates because of
      a disruption of the interrelations between the interrenal gland, the gonads, and
      the thymus. The close association between the gonads and the suprarenals (21) is
      well known. The latter undergo enlargement in pregnancy, ovulation, and
      castration, and the ovaries hypertrophy after suprarenalectomy. Tumors of the
      suprarenals are associated frequently with sex perversion and precocity both in
      the male and female. The interrelation between the gonads and thymus is
      classical, castration before puberty delaying thymus involution for a long time.
      A number of diseases present thymus enlargement among the major pathological
      findings at autopsy. The most outstanding of these are Addison's disease, status
      lymphaticus, and Graves' disease. It is now generally recognized that the
      suprarenal glands play an important r61e in the etiology both of Addison's
      disease and status lymphaticus. Whether the interrenal or the chromophil system
      is primarily involved or whether disturbances in function of both systems are at
      the basis of these diseases is still undetermined. The newer evidence, including
      our own work on lymphoid regeneration following suprarenalectomy supports the
      view that the lymphoid hyperplasia occurring in both Addison's disease and status
      lymphaticus is dependent upon insufficiency of the interrenal system (suprarenal
      cortex). While anatomical studies have not disclosed any constant lesions in the
      suprarenals in Graves' disease, evidence is being accumulated which would
      indicate that functionally these glands also play an important if not a primary
      role in the production of the clinical syndrome of Graves' disease (14, 18, 19).
      We are of the belief that the persistence of the thymus which occurs in status
      lymphaticus, and the regeneration which occurs in Addison's and Graves' diseases,
      are brought about by the same disturbances in glandular interrelations which
      bring about regeneration of the thymus in the experimental animal after
      suprarenalectomy.

PMID- 19868922
TI  - THE CHEMICAL NATURE OF RESIDUE ANTIGEN PREPARED FROM YEAST.
AB  - Residue antigen recognizable by the precipitin test can be prepared from yeast as
      from bacteria. The active material appears to be identical with a complex
      carbohydrate, the "yeast gum" of Salkowski. In the purest form of it obtained
      small amounts of both nitrogen and phosphorus are still present, either as
      impurities or as part of the molecule. The yeast gum is not antigenic in the
      sense of producing antibodies.

PMID- 19868923
TI  - PERSISTENCE OF INSPIRED BACTERIA IN THE LUNGS OF ALCOHOLIZED MICE.
AB  - 1. When mice are exposed to an atmosphere containing certain bacteria in the form
      of a fine mist, the bacteria may be recovered from the deeper respiratory
      passages. 2. Pneumococci which have reached the lungs of normal mice as a result
      of this procedure usually disappear within a few hours and give rise to no
      generalized infection. In mice intoxicated with alcohol, on the other hand,
      pneumococci persist in the lungs for a longer period and fatal speticemia
      frequently follows. 3. Hemolytic streptococci and Bacillus influenzae generally
      persist in the lungs for about 24 hours. In intoxicated mice these organisms do
      not disappear so rapidly from the lungs and generalized infection is much more
      frequent. 4. The experiments yield no evidence as to how alcoholic intoxication
      renders the lungs more permeable to inspired bacteria.

PMID- 19868924
TI  - EFFECT OF FATTY ACIDS ON THE RESISTANCE OF MICE TO TRANSPLANTED CANCER.
AB  - Sodium oleate, oleic acid, linolic acid, and linolenic acid injected into mice in
      suitable amounts induce a material increase in the resistance against subsequent
      transplantation of cancer grafts, although they fail to exert so marked an
      influence on cancer grafts already in place. Sodium palmitate and sodium
      stearate, on the other hand, do not produce immunity, at least in the amounts
      employed in the present study.

PMID- 19868925
TI  - A CARDIOVALVULOTOME.
AB  - 1. A study of the fibrosed and often calcareous condition present in the mitral
      orifice in cases of chronic stenosing rheumatic disease demonstrated that a
      powerful instrument must be developed if we are to apply surgical relief in the
      treatment of the disease. 2. An instrument (cardiovalvulotome) is described which
      actually excises a segment from the mitral orifice and removes this from the
      blood stream. 3. The efficacy of the instrument has been tested by its use on the
      stenotic valves of diseased hearts removed at autopsy. Its feasibility has been
      shown by operations both upon animals and in a single human case.

PMID- 19868926
TI  - OBSERVATIONS ON THE PRESENCE OF A TOXIC SUBSTANCE IN THE BLOOD AND URINE OF
      PATIENTS WITH SCARLET FEVER.
AB  - A series of observations on the blood of patients acutely ill with scarlet fever
      has shown that a toxic substance can be demonstrated in the serum by means of
      intracutaneous injections of the serum in persons who have not had scarlet fever
      and whose serums fail to blanch the rash in scarlet fever. The reaction caused by
      this substance consists of a bright red local erythema, varying from 20 to 70 mm.
      in diameter, of 1 to 4 days duration. The severer reactions are moderately
      indurated and tender, and are followed bypigmentation and desquamation. Control
      injections in persons whose serums blanch the rash in scarlet fever cause no
      reaction. The toxic substance is not neutralized by mixture with a human serum
      which gives a negative blanching test but is readily neutralized by a human serum
      which gives a positive blanching test. It is not neutralized by normal horse
      serum, but is completely neutralized by Dochez's scarlatinal antistreptococcic
      serum. In a limited number of observations on the urine of patients with scarlet
      fever a similar toxic substance has been found in two out of five cases studied.
      Since the toxic substance described appears to resemble the toxic substance found
      in the filtrates of scarlatinal hemolytic streptococcus cultures by Dick and Dick
      and since it is neutralized not only by a blanching human serum but also by
      Dochez's scarlatinal antistreptococcic horse serum, the experiments reported
      support the conception that scarlet fever is a local infection of the throat by a
      particular type of Streptococcus haemolyticus capable of producing a toxin which
      is absorbed and is the cause of the general manifestations of the disease.

PMID- 19868927
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : V. THE EFFECT OF DIET ON HOST RESISTANCE.
AB  - White mice from the Rockefeller Institute breeding room fed on a McCollum
      complete diet, consisting of whole wheat (67.5 per cent), casein (15 per cent),
      milk powder (10 per cent), NaCl (1 per cent), CaCO(3)(1.5 per cent), and butter
      fat (5 per cent) are more resistant to mouse typhoid infection, mercury
      bichloride intoxication, and botulinus toxin than are similar mice fed on bread
      and pasteurized milk supplemented by an oatmeal and buckwheat mixture and dog
      biscuit.

PMID- 19868928
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : VI. THE OXIDATION OF ENZYMES
      IN STERILE EXTRACTS OF PNEUMOCOCCUS.
AB  - 1. Certain enzymes of Pneumococcus are destroyed by oxidizing agents formed when
      sterile extracts of the cellular substances are exposed to air. The carbohydrate
      hydrolyzing enzymes (sucrase, raffinase, inulase, and amylase) are the most
      easily inactivated under these conditions, although the bacteriolytic enzyme is
      also reduced in activity. Similar treatment is without effect upon the active
      concentration of pneumococcus lipase and peptonase. 2. The enzymes which are
      destroyed during the oxidation of unwashed cell extracts are themselves non
      reactive with molecular oxygen. The reactions by which they are destroyed seem to
      represent oxidations of a type similar to those proposed in previous papers for
      the oxidation of hemotoxin and of hemoglobin. 3. A study has been made of the
      relative resistance of different pneumococcus enzymes to heat and to the action
      of hydrogen peroxide. 4. The various enzymes may be arranged in the same order of
      relative resistance whether the rating be made from the standpoint of resistance
      to heat or of resistance to oxidation. Nevertheless, it appears that by a proper
      regulation of conditions of oxidation, certain labile constituents of a mixture
      of cellular enzymes may be inactivated with less effect upon the activity of
      other constituents of the mixture than when inactivation is brought about by
      heat.

PMID- 19868929
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : VII. ENZYME ACTIVITY OF
      STERILE FILTRATES OF AEROBIC AND ANAEROBIC CULTURES OF PNEUMOCOCCUS.
AB  - Sterile filtrates of autolyzed anaerobic cultures of Pneumococcus contain much
      higher concentrations of active endocellular enzymes than do the filtrates of
      autolyzed aerobic cultures. These differences in the enzyme activity of the
      filtrates of aerobic and anaerobic cultures may be explained by a destruction of
      the formed enzymes by oxidation reactions analogous to the destruction previously
      observed during the oxidation of sterile broth extracts of unwashed pneumococcus
      cells. The occurrence of more complete destruction of enzyme activity in
      autolyzed aerobic cultures than in "oxidized" sterile cell extracts is probably
      due to the longer exposure to oxidation products.

PMID- 19868930
TI  - THE INFLUENCE OF THYROIDECTOMY, GONADECTOMY, SUPRARENALECTOMY, AND SPLENECTOMY ON
      THE THYMUS GLAND OF RABBITS.
AB  - Thyroidectomy hastens, while gonadectomy delays, but does not permanently
      prevent, involution of the thymus. Suprarenalectomy alone not only delays
      involution of the thymus and lymphoid tissue but may cause their regeneration.
      Thyroidectomy prevents this reaction even after combined suprarenalectomy and
      gonadectomy. Suprarenalectomy plus gonadectomy is a more powerful stimulus for
      thymus and lymphoid regeneration than either of these influences alone. The
      combined effect of these two factors results in certain lymphoid and thymus
      hyperplasia in rabbits which persists until regeneration of accessory interrenal
      tissue corrects the physiological defect. The syndrome thus experimentally
      produced resembles status lymphaticus and is believed to depend mainly on a
      partial loss of certain functions of the interrenal and sex glands rather than of
      the chromaffin tissue. The normal and abnormal lymphoid and thymic hyperplasias
      of infancy and childhood are believed to be manifestations of a functional
      underdevelopment of the interrenal and sex glands of varying intensity. The so
      called lymphatic constitution which underlies or accompanies exophthalmic goiter,
      Addison's disease, and acromegaly also appears to be dependent on a partial
      suppression of certain functions of the interrenal and sex glands.

PMID- 19868931
TI  - CLASSIFICATION OF THE HEMOLYTTC STREPTOCOCCI BY THE PRECIPITIN REACTION.
AB  - A method is described for the preparation from hemolytic streptococci of extracts
      containing a soluble precipitating substance. By the use of such extracts, it is
      shown that nearly all members of this family yield a common precipitable
      substance. So far, therefore, as concerns the precipitin reaction, the hemolytic
      streptococci form a practically homogeneous group.

PMID- 19868932
TI  - STUDIES IN AGGLUTINATION : II. THE RELATIONSHIP OF REDUCTION OF ELECTRICAL CHARGE
      TO SPECIFIC BACTERIAL AGGLUTINATION.
AB  - 1. The effect of immune serum upon the electrical charge on bacteria has been
      studied. 2. Immune agglutinating serum possesses a specific charge-reducing
      effect which is quantitatively related to the agglutination titer of the serum.
      This effect is lost when the serum loses its agglutinating power, that is after
      adsorption of agglutinin by homologous bacteria; adsorption by heterologous
      organisms does not affect this property. 3. A highly protective, non
      agglutinating serum did not show this specific charge-reducing effect. 4. It is
      suggested that the reaction may have practical diagnostic application. 5. The
      findings of Northrop and De Kruif, that unsensitized and sensitized bacteria
      agglutinate only when the charge on the bacteria has been reduced to a critical
      potential zone lying between +15 and -15 millivolts, have been confirmed in the
      case of all electrolytes tested except Na(2)HPO(4). 6. When Na(2)HPO(4)or
      phosphate buffer solutions are used as electrolytes, specific bacterial
      agglutination occurs at negative charges well above -15 millivolts, and with
      serum in high dilution, specific agglutination takes place without any observable
      reduction of charge.

PMID- 19868933
TI  - STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION : III. THE INFLUENCE OF SPECIFIC
      ANTIPNEUMOCOCCUS SERUM ON THE GROWTH-INHIBITORY AND BACTERICIDAL ACTION OF NORMAL
      SERUM-LEUCOCYTE MIXTURES.
AB  - Using the method described in an earlier publication for testing the growth
      inhibitory and bactericidal activity of serum-leucocyte mixtures for the
      pneumococcus, a study has been made of the action of antipneumococcus serum added
      to the serum and leucocytes of the rabbit, which alone lack the power to inhibit
      pneumococcus growth. It was found that the additiori of relatively small
      quantities of immune serum to a mixture of rabbit serum and washed rabbit
      leucocytes conferred on this mixture marked growth-inhibitory and pneumococcidal
      powers. The effect of the immune serum was found to be quantitative in nature.
      Beyond a certain point progressive dilution of the serum resulted in a
      corresponding decrease in the degree of growth inhibition, but this property of
      the immune serum did not disappear until a high dilution was reached. The
      leucocytes were also found to exert their effect quantitatively. Within certain
      limits the number of pneurnococci killed was dependent on the quantity of them
      present. Tests comparing the action of immune serum in the rabbit serum-leucocyte
      tubes with their protective action in mice showed a close parallelism between
      these two effects; that is to say, an immune serum showing marked protective
      properties for mice was likewise effective in high dilution in the in vitro test,
      and vice versa.

PMID- 19868934
TI  - STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION : IV. A SIMPLIFIED AGITATOR FOR GROWTH
      INHIBITION TESTS WITH SERUM-LEUCOCYTE MIXTURES; AND CERTAIN MODIFICATIONS IN THE
      TECHNIQUE OF THE TEST.
AB  - A simplified and compact agitator for growth inhibition tests with serum
      leucocyte mixtures has been described. Several modifications have been made as
      well in the technique of the test, which have eliminated occasional
      irregularities that necessitated discarding the results of the individual
      experiment. Such irregularities were found to be due chiefly to injury of the
      pneumococci brought about by prolonged suspension in gelatin-Locke's solution
      which resulted in failure of the organisms to grow in the control serum-leucocyte
      tubes. This deterioration of the pneumococcus suspension may be greatly lessened
      or entirely prevented by the addition of a small quantity of a balanced phosphate
      mixture to the gelatin-Locke's solution. The use of small tubes made of Pyrex
      glass has also eliminated the former, not infrequent, occurrence of early
      hemolysis which was sometimes intense enough to disturb the results of the test.
      It has been found that washed rabbit leucocytes, suspended in their homologous
      serum, may be kept in the ice box for as long a period as 2 days without showing
      any apparent diminution of their functional activity in the serum-leucocyte test.

PMID- 19868935
TI  - STUDIES ON THE BIOLOGY OF STREPTOCOCCUS : IV. THE OCCURRENCE OF STREPTOCOCCUS
      SCARLATINAE IN CONVALESCENCE AND IN THE COMPLICATIONS OF SCARLET FEVER.
AB  - 1. A group of streptococci which agglutinate with scarlatinal immune sera has
      been isolated from the throats of 65 per cent of cases of scarlet fever during
      the 1st week of the disease. 2. Strains of hemolytic streptococci belonging to
      this group have been isolated from the throats of patients at the termination of
      quarantine (30 days). 3. Hemolytic streptococci are found most frequently in the
      throat in convalescent patients in whom the tonsillar inflammation has not
      entirely subsided. 4. The complications occurring in scarlet fever may be due to
      the original scarlatinal strain or may be the result of a secondary infection
      with pyogenic strains of streptococci.

PMID- 19868936
TI  - ALLERGIC IRRITABILITY : THE FORMATION OF ANTI-SHEEP HEMOLYTIC AMBOCEPTOR IN THE
      NORMAL AND TUBERCULOUS GUINEA PIG.
AB  - The guinea pig infected with virulent tubercle bacilli develops much more anti
      sheep amboceptor than do controls when given like amounts of sheep red blood
      corpuscles. The curve of antibody production in the guinea pig when treated with
      sheep red blood corpuscles shows a departure from curves previously determined in
      other animals. These facts were ascertained as part of an effort to learn mbre of
      the functional nature of the inheritable factors controlling natural resistance
      to disease. The nature of some of the problems involved is outlined, and the
      limited bearing of the experiments on these is discussed.

PMID- 19868937
TI  - THE PRODUCTION OF PERSISTENT ALOPECIA IN RABBITS BY ROENTGEN RADIATION; A STUDY
      OF THE MINIMUM DOSE REQUIRED AND THE CONSISTENCY OF THE REACTION.
AB  - Seven areas on the abdomen of each of fourteen rabbits were exposed to soft
      Roentgen radiation of constant quality in doses varying, in the region of the
      value critical for the production of persistent alopecia, by regular steps of
      about 4 per cent. Without exception the critical dose was found to lie between
      two such values, the upper limit being represented by exposures on eight of the
      animals and the lower on ten of them. With certain reservations, the critical
      dose corresponds to the production of 2.04 x 10(15) ions of either sign per gm.
      of tissue.

PMID- 19868938
TI  - ATTEMPTS TO TRANSMIT RHEUMATIC FEVER TO RABBITS AND GUINEA PIGS.
AB  - In a series of attempts to transmit a virus from patients in the acute stages of
      rheumatic fever, twenty-seven rabbits and fourteen guinea pigs were inoculated
      with one of the following materials: whole blood, serum, joint fluid, pleural
      fluid, throat washings, suspensions of tonsil tissue. Subsequent transfer
      inoculations from animal to animal brought the total number of animals employed
      in the experiments to 67 rabbits and 40 guinea pigs. Only two animals developed
      an acute non-bacterial arthritis. No other evidence of successful transmission of
      the disease was obtained. In about one-half of the rabbits and two-thirds of the
      guinea pigs myocardial lesions were encountered which consisted of interstitial
      accumulations of lymphocytes and endothelial cells. Similar lesions were found in
      control animals.

PMID- 19868939
TI  - SPONTANEOUS INTERSTITIAL MYOCARDITIS IN RABBITS.
AB  - The hearts of thirty-four apparently healthy adult rabbits were carefully studied
      microscopically. Twenty, or 60 per cent, contained lesions consisting of
      lymphocytes and endothelial leucocytes invarying proportions, to which were
      sometimes added polymorphonuclear eosinophils, plasma cells, and fibroblasts in
      small numbers. The lesions occurred most frequently between the muscle fibers of
      the papillary muscles and ventricular walls, and occasionally beneath the
      endocardium and epicardium. No microorganisms or cell inclusion bodies were found
      in the lesions.

PMID- 19868940
TI  - THE BLOOD PLATELETS IN PNEUMOCOCCUS INFECTIONS.
AB  - 1. A study was made of the behavior of the blood platelets during the course of
      pneumonia in man, as also in several rabbits experimentally infected with
      pneumococci. 2. The number of platelets begins to diminish after the infection
      has become established. A thrombopenia occurs during the febrile period.
      Immediately following the onset of the crisis in lobar pneumonia or after the
      temperature begins to fall by lysis, the platelets begin gradually to increase in
      number. In the postfebrile period, the platelet count increases until the normal
      number is greatly exceeded, and there is a return to the normal number only after
      about 2 weeks. 3. Sequelae, characterized by fever, following pneumonia are
      accompanied by a renewed diminution in the number of platelets. After subsidence
      of the temperature their number usually increases until the normal is again
      exceeded. 4. The platelets in general are smaller and contain more granules
      during the thrombopenic stage of pneumonia. 5. Intravenous injection of
      antipneumococcus serum during pneumonia ordinarily produces no variation in the
      number of platelets.

PMID- 19868941
TI  - PRODUCTION OF IMMUNITY IN MICE BY INHALATION OF PNEUMOCOCCI.
AB  - 1. A definite degree of active immunity can be induced in mice through the
      repeated inhalation of live pneumococci. 2. Only slight immunity is induced in
      mice by the repeated inhalation of killed organisms.

PMID- 19868942
TI  - PRECIPITATION AND COMPLEMENT FIXATION REACTIONS WITH RESIDUE ANTIGENS IN THE NON
      HEMOLYTIC STREPTOCOCCUS GROUP.
AB  - The applicability to the non-hemolytic streptococci of the technique used for the
      extraction of a soluble precipitating substance from the hemolytic streptococci
      is demonstrated. With this substance as antigen, it is demonstrated by means of
      precipitation and complement fixation that the non-hemolytic streptococci form an
      antigenically distinct, but entirely heterogeneous group. Such cross-reactions as
      do occur within this group are not useful in the systematic classification of
      these organisms.

PMID- 19868943
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : VI. VARIATIONS IN GROWTH AND
      MALIGNANCY OF TRANSPLANTED TUMORS. PART 1. RESUTLTS OF TRANSPLANTATION FOR THE
      FIRST TWENTY GENERATIONS.
AB  - A report is given of the results obtained by intratesticular inoculation of a
      malignant tumor of the rabbit based on a study of the first twenty generations.
      The subject is presented from the standpoint of variations in growth and
      malignancy as they occurred with continued transplantation. Essential features of
      the experimental conditions and of clinical and postmortem observations are
      condensed and recorded graphically. On analyzing the results of these
      experiments, it was found that many changes had occurred in the behavior of the
      tumor during transplantation, but that the changes were of a very irregular
      character and as a rule did not proceed constantly in any given direction.
      Moreover, the evidence as to the effect of transplantation on the growth and
      malignancy of the tumor was contradictory in that there was a great deal of
      evidence to show that there had been a decided increase in the activity and
      capacity for growth on the part of the tumor cells. But, with the exception of a
      few generations, there was an apparent reduction in the incidence and percentage
      distribution of secondary tumors, while the death rate was unaltered or actually
      diminished. It was believed that this paradoxical situation afforded a basis for
      an explanation of the results that had been obtained by transplantation.

PMID- 19868944
TI  - STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT : VI. VARIATIONS IN GROWTH AND
      MALIGNANCY OF TRANSPLANTED TUMORS. PART 2. FACTORS INFLUENCING THE RESULTS OF
      SERIAL TRANSPLANTATION.
AB  - The results of transplantation, as recorded in the first section of the paper,
      are analyzed from the standpoint of the influence of the factors of serial
      passage, the material used for inoculation, the age and breed of the animals, and
      the time or season at which the experiments were carried out. The material used
      for the inoculation of different groups of animals appeared to have comparatively
      little effect on the ultimate results. The character of the animals used was
      found to be a factor of more importance in that the tumor displayed definite
      peculiarities of growth and malignancy referable to age and to breed or color
      markings. Still, it seemed unlikely that any of these factors would account for
      the variations in growth and malignancy that had been observed. After considering
      the various possibilities presented, it appeared that the principal factors
      concerned in determining the results of transplantation were adaptation to
      passage and variations in the conditions of season and weather that prevailed
      during the time the experiments were being carried out-the one affecting the
      energy of cell growth and the other affecting animal economy.

PMID- 19868945
TI  - THE INFLUENCE OF THE SUPRARENAL GLAND ON THE THYMUS : II. DIRECT EVIDENCE OF
      REGENERATION OF THE INVOLUTED THYMUS FOLLOWING DOUBLE SUPRARENALECTOMY IN THE
      RAT.
AB  - 1. Regeneration of involuted thymuses of old rats follows double suprarenalectomy
      in this species with great constancy. 2. Partial thymectomy alone does not induce
      compensatory secondary hyperplasia in involuting glands. 3. Regeneration of the
      thymus following suprarenalectomy would appear to be completed in most rats in
      about 2 weeks; and it probably begins in the medulla.

PMID- 19868946
TI  - THE EFFECT OF HEAT ON FLAGELLAR AND SOMATIC AGGLUTINATION.
AB  - 1. Heat at 70 degrees C. destroys the form of the flagella and their ability to
      combine with flagellar agglutinins but it does not destroy their antigenic nature
      since they can still generate flagellar agglutinins in the animal body. 2. Heat
      at 70 degrees C. and even at 120 degrees C. in the autoclave does not destroy the
      forms of the bacilli themselves nor their ability to become agglutinated and to
      absorb agglutinins. 3. Somatic agglutinins are destroyed to a considerable extent
      by heat at 70 degrees C. and completely destroyed by heat at 75 degrees C. 4.
      Heat at 70 degrees C. causes little or no destruction of flagellar agglutinins
      but a temperature of 75 degrees C. changes the agglutinins so that they react
      more slowly and produce a slightly lower reaction with a zone of inhibition in
      the stronger dilutions.

PMID- 19868947
TI  - THE PENETRATION OF BACTERIA THROUGH CAPILLARY SPACES : IV. A KINETIC MECHANISM IN
      INTERFACES.
AB  - The dark-field microscope may be used to observe directly the characteristics of
      composite films. The liquid phases, one or both of them containing suspended
      solid particles as test objects (in these experiments bacteria were used), are
      spread between slide and cover-glass and examined with any desired lenses. The
      liquid-liquid interfaces appear as bright lines and the solid particles as
      shining motes. An interfacial kinetic mechanism has been observed in films of all
      composition studied. The bacteria are transported along the phase boundary lines
      in a striking and characteristic manner and quite independently of movements in
      the adjoining organic or aqueous phases. These movements in the interface are
      interpreted as essentially due, according to the composition of the films, to
      local inequalities in interfacial surface tension, or to minute currents from
      mixing of the two phases across and along their boundary line, or to both forces
      acting together. The bacteria (non-motile in these experiments) reached the
      interface by brownian movement or currents or shifts in the position of the
      boundary line. Once in the interface they tended to remain, and accumulated
      there, in instances where the liquid-liquid interfacial tension was high at
      least, in higher concentration than in the contiguous phases. Bacteria could,
      however, escape from the interface in a variety of ways detailed above. With
      liquids which differ markedly in interfacial tension and miscibility with water,
      these properties may be correlated with the characteristics of the preparation.
      With cyclohexane-water films, for instance, (immiscible, interfacial tension
      high), the boundary was less readily drawn out into projections, the interfacial
      trapping mechanism was more efficient, and brownian movement of bacteria in the
      interface was less free than with cyclohexanol-water films (miscible, interfacial
      tension low). Analysis of the mechanism of the phenomena herein described will be
      given in the paper following.

PMID- 19868948
TI  - CERTAIN INTERFACIAL TENSION RELATIONS AND THE BEHAVIOR OF BACTERIA IN FILMS.
AB  - TO ACCOUNT FOR THE BEHAVIOR OF A SOLID PARTICLE IN THE INTERFACE BETWEEN TWO
      FLUIDS IT IS NECESSARY TO CONSIDER, AS INDICATED BY CLARK MAXWELL, THREE SURFACE
      TENSIONS: T(so), the tension in the interface between the solid particle and the
      organic phase; T(sw), the tension in the interface between solid particle and
      aqueous phase; and T(ow), the organic phase-water interfacial tension. If T(so) >
      T(sw) + T(ow), (2), the stronger solid-organic phase tension should pull the line
      of intersection of the three phases around the periphery of the solid particle
      until the particle is completely enveloped in the water phase. If T(sw) > T(ow) +
      T(ow) (3), the solid-water tension should pull the line of meeting of the phases
      about the particle until it is enveloped in the organic phase. If See PDF for
      Equation the particle should be stable in the interface, only leaving it when
      mechanical work overcomes the equilibrium due to the balance of interfacial
      tensions. The ordinary bacteria used have been stable in the interfaces between
      water or aqueous solutions and all organic liquids tested; i.e., condition (4)
      obtains. In preparations in which T(ow) is large, stability has been found by
      experiment to be greater than when T(ow) is small, as follows from condition (4).
      The force, dependent upon condition (4), which holds bacteria in the liquid
      liquid interface, and the force, dependent upon unequal distribution of tension
      in the liquid-liquid interface, which causes bacteria to glide along the
      interface, prove to be of the same order of magnitude as the force due to
      bacterial flagella. Interfacial tensions or its own motility may dominate the
      movement of the bacterium, according to circumstances. When bacteria thresh their
      way out of the interface, escape is into the aqueous phase. Acid-fast bacteria
      possess very low or, in some cases, no stability in the interface, passing easily
      or even spontaneously into the organic phase. Good evidence has been advanced by
      other workers to indicate that the surfaces of ordinary bacteria contain many
      polar radicals; on the other hand, the acid-fast microorganisms are coated with
      predominantly non-polar substances. It follows from known principles, therefore,
      that T(sw) should be greater than T(sw) with ordinary bacteria, and T(sw) should
      be greater than T(so) with acid-fast bacteria. Consideration of relations (2) and
      (3) above will show that these conditions should result in the differences in
      behavior of acid-fast and ordinary bacteria actually found by experiment. The
      theoretical and experimental data here developed contradict the theoretical
      formulations of the surface tension factor in phagocytosis advanced by Rhumbler
      and by Tait and substantiate those of Fenn.

PMID- 19868949
TI  - TISSUE RESISTANCE AND THE CAUSE OF PERMANENT ACQUIRED IMMUNITY.
AB  - 1. The resistance against toxic products of typhoid bacilli of the heart tissues
      of typhoid-immune animals is greater than that of nonimmunized animals. 2. The
      acquired increase of resisting power is specific. 3. The increased resistance is
      not caused by antitoxin, but by a specific biological alteration of tissue cells.
      4. It is maintained that permanent acquired immunity, at least in typhoid,
      instead of being due principally to antibodies, is caused by a lasting specific
      increase of resisting power acquired by the tissue cells against the toxic
      products of bacteria. 5. This theory seems to hold good with other infectious
      diseases in which one attack conveys permanent immunity.

PMID- 19868950
TI  - ON THE NATURE OF THE HEAT-LABILE SUBSTANCE ("V") REQUIRED FOR THE GROWTH OF THE
      BACILLUS OF PFEIFFER.
AB  - It has been shown in several experiments that the heat-labile, growth-promoting
      factor "V" found in the blood of animals does not diminish or disappear when the
      animals are kept on vitamine B-free diet. The titer of the "V" substance present
      in the blood of normal animals is undiminished in animals showing severe signs of
      polyneuritis even to the time of their death. The antipolyneuritic factor of
      vegetable food, designated as vitamine B, is found to be considerably more heat
      stable than is the "V" substance concerned in promoting the growth of Pfeiffer's
      bacillus.

PMID- 19868951
TI  - THE RELATION OF DOSE OF BACTERIA TO GROUP INFECTION.
AB  - A study has been made of the peritoneal reaction in mice after injection of
      different bacteria in graded dose. Organisms were employed to which the animals
      were fairly resistant. Under these conditions it was found that as the dosage was
      decreased a more or less critical point was reached below which infection failed
      to be initiated. The possible clinical bearings of this observation are
      discussed.

PMID- 19868952
TI  - THE RELATION OF VEGETATIVE ACTIVITY OF BACTERIA TO PATHOGENICITY.
AB  - The experiments which have been reported show that distinct differences exist
      between relatively young cultures of bacteria and the same strains during the
      period of decline as regards invasive power and pathogenicity, and that these
      differences must be distinguished clearly from specific alterations in virulence
      such as those produced by animal passage. The exact interpretation of these
      observations is not, however, perfectly clear. We were inclined to believe that
      simple alterations in vegetative activity might account for the differences which
      have been described, but to what extent the results have been due to injury to
      the bacteria by products of culture growth it is impossible to say, and further
      work will be necessary to settle this point. At any rate the experiments seem to
      bear definitely on the problem of infection in as far as they show that purely
      temporary modifications See PDF for structure of growth activity whether or not
      brought about by specific injury lead to changes in invasiveness which are quite
      analogous to the test-tube phenomenon of lag. It has previously been shown that
      there exists in the upper air passages a mechanism by means of which foreign
      particles and bacteria can be eliminated within a few hours. It seems highly
      likely on the basis of the present work that bacteria entering in an inactive
      growth phase-for example dried in dust or perhaps from a chronic carrier-may be
      disposed of before activity can be resumed, whereas organisms introduced in the
      stage of active growth-as from a case of acute disease-may be able to take
      advantage of a portal of entry. It is further possible that these experiments may
      have some bearing on the genesis of epidemics, especially as regards the
      preepidemic phase, and these matters will be discussed at another time.

PMID- 19868953
TI  - THE OCCURRENCE OF GASTRIC LESIONS IN RATS : THEIR RELATION TO DIETARY DEFICIENCY
      AND HAIR INGESTION.
AB  - Ulcerative lesions of the rumen with papillary epithelial hyperplasia occur in a
      large proportion of rats maintained on a deficient diet, and are rarely, if ever,
      present when the diet is complete. It has not been possible to ascribe the
      lesions to lack of any of the known dietary components. The fact that rats on
      improper diets tend to eat hair, that hair fragments have been found in a number
      of instances embedded in the ulcers, and surrounded by a definite inflammatory
      reaction, and finally, that the ulcers have been experimentally produced in rats
      on a complete diet, when chopped hair was added to the food, lead us to believe
      that the ingested hair is an important factor in the causation of the lesions.
      Whether the hair splinters act merely as mechanical irritants, or as the carriers
      of an infective agent, has not been determined. It is probable, moreover, that
      the deficient diets in some way that we do not as yet understand, intensify the
      injury caused by the hair. However produced, the lesions are so frequently found
      that they should be taken into account in experimental work on rats, especially
      in judging of the effects of dietary influences by the weight curves. That the
      presence of severe ulcerative lesions in the prostomach must unfavorably affect
      the general nutrition of an experimental animal, seems beyond question.

PMID- 19868954
TI  - EXPERIMENTAL PRODUCTION OF PNEUMOCOCCUS PNEUMONIA IN MICE BY THE INHALATION
      METHOD.
AB  - 1. Non-immune mice which are alcoholized and die of septicemia following exposure
      to a spray of virulent pneumococci rarely show any localization of infection in
      the lung. 2. Mice which have been partially immunized by previous inhalations of
      living or killed pneumococci and which while alcoholized are exposed to an
      atmosphere of virulent pneumococci often develop a pneumococcus lobar pneumonia.
      3. Mice which have been rendered relatively immune to one type of pneumococcus
      may frequently develop lobar pneumonia after the inhalation of pneumococci of
      another type.

PMID- 19868955
TI  - PATHOLOGY OF EXPERIMENTAL PNEUMOCOCCUS PNEUMONIA IN MICE.
AB  - 1. The administration of alcohol produces no evident histological changes in the
      lungs of mice. 2. Following inhalations of pneumococci the organisms are not
      visible histologically in the lungs of mice either in the bronchi or alveoli. 3.
      In partially immunized mice which have been exposed to a pneumococcus spray while
      alcoholized, true lobar pneumonia not infrequently develops. 4. The primary
      lesion of such lobar pneumonia in mice is an interstitial inflammation of the
      alveolar wall and the infection spreads in the interstitial tissue like a
      cellulitis. 5. A tentative explanation of the "lobar" distribution of
      pneumococcus pneumonia is offered.

PMID- 19868956
TI  - THE INFLUENCE OF THE SUPRARENAL GLAND ON THE THYMUS : III. STIMULATION OF THE
      GROWTH OF THE THYMUS GLAND FOLLOWING DOUBLE SUPRARENALECTOMY IN YOUNG RATS.
AB  - 1. Double suprarenalectomy in growing rats is an additional stimulus for thymic
      growth and brings about marked prepubertal hyperplasia of this gland. 2. Our
      results on young rats suggest that the suprarenal cortex may be a factor in the
      excessive thymic hyperplasias seen in infants and children.

PMID- 19868957
TI  - THE PRODUCTION OF AN EXOTOXIN BY CERTAIN STRAINS OF STAPHYLOCOCCUS AUREUS.
AB  - 1. The sterile Berkefeld filtrates of broth cultures of certain strains of
      Staphylococcus aureus have a selective poisonous action for the skin of rabbits.
      2. The poison is thermolabile, being completely destroyed when heated to 55
      degrees C for 1 hour. 3. The poison when injected intradermally into rabbits
      stimulates the production of antitoxin. We therefore conclude that the poison is
      a soluble toxin.

PMID- 19868958
TI  - A FILTERABLE VIRUS INFECTION OF RABBITS : I. ITS OCCURRENCE IN ANIMALS INOCULATED
      WITH RHEUMATIC FEVER MATERIAL.
AB  - 1. Blood and joint fluid of patients suffering from rheumatic fever were
      inoculated into the testicles of rabbits, and transfers were made from testicle
      to testicle at varying intervals. In three series, in none of which were the
      periods between the transfers longer than 4 days, a virus was recovered which
      produced acute orchitis in rabbits. The virus could be indefinitely propagated
      from rabbit to rabbit. 2. Intradermal inoculation of the virus led to the
      appearance of raised erythematous lesions in 3 to 6 days. 3. Intrathoracic
      inoculations near the heart led to a fibrinous pericarditis in three out of five
      rabbits, and to a myocarditis in one. 4. Nuclear inclusion bodies staining pink
      with eosin were found in the lesions in the testis, skin, pericardium, and heart
      muscle. 5. Rabbits inoculated into skin or testes were refractory, 2 weeks later,
      to further intradermal inoculations; after this interval their serum had
      developed the power to neutralize the virus in vitro. 6. The virus can be
      preserved in 50 per cent glycerol for at least 18 days. It can be preserved after
      freezing and drying for at least 8 days and probably for 10 weeks. 7. Cross
      immunity tests point to the identity of the virus with that described by Rivers
      and Tillett in their studies on chicken-pox as Virus III. 8. These facts together
      with the failure of rheumatic fever sera to neutralize the virus indicate that it
      bears no etiologic relationship to rheumatic fever.

PMID- 19868959
TI  - A FILTERABLE VIRUS INFECTION OF RABBITS : II. ITS OCCURRENCE IN APPARENTLY NORMAL
      RABBITS.
AB  - 1. In two, and possibly four, of six transmission series of rabbits inoculated in
      the beginning with the blood of apparently normal rabbits a virus was recovered
      having the same properties as that recovered from series originally inoculated
      with material from rheumatic fever patients. The virus was immunologically
      identical with Rivers-Tillett Virus III and with that obtained from the rheumatic
      fever series. In conducting the control series precautions were taken to prevent
      infection of rabbit stock from known sources of the virus. 2. Treating rabbits
      with benzene does not appreciably increase their susceptibility to infection with
      the virus. 3. The virus is probably a parasite of the domestic rabbit but up to
      the present time the natural course of the infection in that animal is unknown.

PMID- 19868960
TI  - STUDIES ON THE TOTAL BILE : VII. CONDITIONS INFLUENCING THE CALCIUM CONTENT OF
      THE BILE.
AB  - A day to day study has been made of the calcium content of the total liver bile
      of dogs intubated under sterile conditions. The concentration of this element in
      the bile is fairly constant under physiological conditions which do not involve
      wide fluctuations in the secretory output. It follows that the calcium yield for
      each 24 hour period in general varies directly with the amount of the bile. But
      when this amount becomes greatly lessened, as the result of fasting, the
      concentration of calcium becomes markedly increased, though not sufficiently so
      to compensate for the lessened volume. When the bile amount rises much above the
      average after the ingestion of food in quantity, the calcium content, unlike that
      of pigment, does not become correspondingly diminished, but tends to remain the
      same as ordinarily. Hence when great amounts of bile are put out, so too are
      relatively great amounts of calcium. This is not because of the increased
      ingestion of the element. For neither feedings with bone meal, nor the
      administration of large quantities of calcium salts intravenously or by mouth has
      any effect to alter the biliary output of calcium. The normal gall bladder, far
      from secreting calcium into the bile, as some have supposed, acts to remove this
      element from the secretion, and removes carbon dioxide as well. The "white bile,"
      which is a specific secretion of the bile ducts, contains but little calcium,
      like the mucous secretions from elsewhere in the body. The concentration is only
      slightly greater than that in the blood plasma, and contrasts significantly with
      the high concentration to be noted in true bile of the fasting animal. Evidently
      the greater portion of the bile calcium must be secreted, not by the duct walls,
      but by the liver itself. The findings have an evident bearing on the problem of
      cholelithiasis.

PMID- 19868961
TI  - STUDIES UPON THE ETIOLOGY OF DENGUE FEVER : I. EXPERIMENTAL TRANSMISSION TO THE
      LOWER ANIMAL.
AB  - The dengue cases studied during this epidemic were, as a whole, typical examples
      of the disease. The onset was sudden, often of a violent character, ushered in
      with severe headache and backache, vague pains throughout the body, and fever
      ranging from 101-105 degrees F. On the 2nd or 3rd day a maculopapular eruption
      appeared, generally on the neck, chest, and arms, but sometimes more widely
      disseminated. In most instances the fever remained for 3 or 4 days, after which
      it dropped to normal to rise again in 24 to 48 hours. The secondary rise, while
      occasionally higher than the primary one, was as a rule of a milder character. A
      few cases occurred in which marked jaundice existed. As reported for previous
      epidemics, no fatalities were recorded and hence no human material for
      histological study was available. Those cases caught in the fastigium of the
      disease were selected when possible as a source of material. The leucocytic count
      in all of the observed human cases was below normal. The experiments herein
      reported upon the transmission of dengue fever to the guinea pig are based upon
      the use of material secured from sixteen typical human cases of the disease, and
      upon the inoculation of many animals. Of the 143 animals used for the initial
      transmission, 42, representing eleven human cases out of the sixteen studied,
      reacted in a characteristic manner. The reaction occasioned in these animals by
      the inoculations closely resembles the symptoms seen in human dengue, differing
      only in the absence of exanthem. The primary pyrexia following regularly after a
      definite incubation period of 2 to 5 days, the secondary rise in temperature
      after a 24 to 48 hour remission ("saddleback"curve), and the concomitant fall in
      the circulating leucocytes present a syndrome identical with that of the human
      disease. Dark-field and special tinctorial studies of the dengue material, both
      human and experimental, have failed to reveal any visible spirochetal
      microorganism. It seems unlikely that an organism of any proportion other than a
      minute body is the excitant of dengue fever. In the experimentally induced
      infection of the guinea pigs by the inoculation of dengue virus there occurs a
      rather constant and characteristic gross alteration of the lymphoid tissues, and
      of the spleen especially, which latter organ often attains a size three to four
      times that of the normal. Enlarged lymph glands in the peritoneal areas are also
      a fairly constant finding. The adrenal glands occasionally show marked
      enlargement. The histopathology consists of an endothelial proliferation
      occurring chiefly in connection with the Malpighian bodies of the spleen and the
      germinal centers of the lymph nodes. Experiments performed with a view of
      demonstrating the protection afforded the recovered guinea pig were somewhat
      confused by delayed fatalities or later intercurrent infections to which the
      dengue-inoculated animal seems highly susceptible. The constant and uniform
      results for all the positive cases indicate that the virus of dengue fever is not
      only transmissible to the guinea pig but is susceptible to propagation in this
      species through an undetermined number of successive generations. After certain
      of the virus strains had been propagated through four or more generations they
      were discontinued. Two strains, however, have been continued for 36 and 45
      generations respectively. The equally successful results with Berkefeld filtered
      material and whole defibrinated blood indicate that the excitant of dengue fever
      belongs in the group of filterable viruses.

PMID- 19868962
TI  - STUDIES UPON THE ETIOLOGY OF DENGUE FEVER : II. CULTIVATION AND NATURE OF THE
      VIRUS.
AB  - We have described the cultivation of a minute organism, upon the special media
      devised by Noguchi for growing spirochetal organisms, that gives rise to pyrexial
      and leucocytic reactions in the guinea pig. The reaction in the animal following
      the injection of culture filtrate is identical with that induced by the
      inoculation of human dengue blood. While it is possible, it is hardly probable
      that the infection of animals with cultures of this microorganism several
      generations removed from the original is due to a mechanically transferred virus
      with which the visible microorganism cultivated became accidentally associated.
      Furthermore, it is unlikely that such a virus would remain viable and be carried
      over to subcultures in sufficient numbers to infect the animal. The
      microorganisms appear in culture as globoid bodies measuring from 0.1 to 0.3micro
      in diameter and are arranged singly, in pairs, and in short chains. They readily
      pass through the Berkefeld filter (N and V) and the filtrate gives rise to a
      characteristic reaction in the inoculated guinea pig. The filtrate yields in
      subplants the same globoid bodies of the original culture. Initial cultures have
      been obtained directly from the blood of the human case as well as from the blood
      of guinea pigs reacting to the human material. However, only early generations
      retain the degree of virulence necessary to cause the experimental reaction, the
      culture of remote generation failing to infect. As far as known this minute
      organism has characters in common with the globoid bodies of Flexner and Noguchi
      obtained from cases of poliomyelitis. In plasma semisolid medium the striking
      feature indicative of growth is colonization, which in itself serves to
      differentiate the opalescence of the medium occasioned by disintegration of the
      contained tissue. As regards the presence of spirochetal organisms in the blood
      of dengue fever, we may state that examination was made of the material from
      human cases and from. a large number of inoculated animals. Despite the most
      careful search with the dark-field microscope and repeated examinations of blood
      specimens stained by the best methods, we have been unable to find any
      demonstrable spiral organism in the blood of dengue patients or in the
      experimentally inoculated animal. The minute organism herein described is
      frequently present in cultures of the blood of human dengue and of animals
      inoculated with dengue material. The inoculation of the culture into guinea pigs
      produces a response comparable to that occurring in the human case, and that
      induced by the injection of human dengue blood in guinea pigs. While we are of
      the opinion that the anaerobic globular bodies described may bear etiological
      relationship to dengue, we realize that further proof and confirmation of our
      work are required to establish the connection.

PMID- 19868963
TI  - STUDIES ON THE MATURATION OF MYELOBLASTS INTO MYELOCYTES AND ON AMITOTIC CELL
      DIVISION IN THE PERIPHERAL BLOOD IN SUBACUTE MYELOBLASTIC LEUCEMIA.
AB  - 1. Myeloblasts can be discriminated in the supravital technique by the great
      numbers of tiny mitochondria in the cytoplasm and the absence of any other
      vitally stainable substance. 2. There are three stages in the maturation of
      myelocytes. 3. These three phases can be correlated with three types of the
      oxidase reaction. 4. One case of myeloblastic leucemia showed such an amount of
      an abnormal type of amitosis as to suggest the disordered cell division of
      neoplasms. 5. In this case transfusions were correlated with a maturation of
      myeloblasts into myelocytes, with an increase of the oxidase reaction, and with
      an increase in amitosis.

PMID- 19868964
TI  - FACTORS CONCERNED IN THE POLYCYTHEMIA PRODUCED BY THE SUBCUTANEOUS INJECTION OF
      EPINEPHRINE.
AB  - The subcutaneous injection of epinephrine in doses of 1 mg. per kilo brings about
      a polycythemia, an increase in reticulocytes, and an increase in young forms of
      polymorphonuclear leucocytes. The polycythemia is no doubt in part a
      concentration phenomenon, but the presence of these young cells in increasing
      numbers is believed to be evidence that there is at the same time a discharge of
      cells from the blood-forming organs, due to the effect of the drug upon them. A
      similar effect is obtained by continued stimulation of the peripheral ends of the
      cut sciatic nerves in the curarized animal.

PMID- 19868965
TI  - EXPERIMENTAL HIGH INTESTINAL OBSTRUCTION IN THE MONKEY.
AB  - The blood findings in five monkeys after experimental high intestinal obstruction
      are reported. All animals showed the marked rise in non-protein nitrogen
      characteristic of intestinal obstruction in man and the dog. Two monkeys showed a
      very marked drop in chlorides, the others a less marked fall. Coincident with the
      change in chlorides there is a rise in the CO(2)-combining power. The uric acid
      and creatinine showed no typical changes. No vomiting was observed. This
      emphasizes the fact that vomiting alone does not account for the fall in blood
      chlorides characteristic of intestinal obstruction.

PMID- 19868966
TI  - THE DISTRIBUTION OF CHLORIDES IN THE BLOOD OF THE DOG AFTER EXPERIMENTAL
      INTESTINAL OBSTRUCTION.
AB  - THE RESULTS OF SIMULTANEOUS CHLORIDE DETERMINATIONS IN WHOLE BLOOD, IN PLASMA,
      AND IN CELLS OF THE DOG AFTER EXPERIMENTAL INTESTINAL OBSTRUCTION ARE PRESENTED,
      AND THE CHLORIDE CONTENT OF WHOLE BLOOD AND OF PLASMA IS COMPARED BY TWO METHODS
      OF ESTIMATION: the iodometric titration on protein-free filtrate, and the
      digestion technique of Van Slyke. The chloride as determined on protein-free
      filtrate checks closely with that as determined by the digestion procedure. The
      iodometric determination shows accurately the level of chlorides in the blood.
      The total change in the chloride store of the body is best reflected in
      determinations on whole blood. In intestinal obstruction the retained chloride is
      not present in the blood in some undetermined form.

PMID- 19868967
TI  - THE SODIUM CONTENT OF THE BLOOD OF THE DOG AFTER EXPERIMENTAL INTESTINAL
      OBSTRUCTION.
AB  - Sodium determinations on the blood of ten dogs after experimental obstruction of
      the jejunum are reported. The average sodium content of the plasma of the normal
      dog is 336 mg. per 100 cc. There is relatively little change in the sodium
      content of the blood plasma after the intestine is obstructed, even with marked
      changes in the chloride and bicarbonate. The whole blood sodium tends to rise
      after intestinal obstruction. The increase in bicarbonate ions does not fully
      compensate for the decrease in chloride ions. After intestinal obstruction there
      is a larger amount of sodium in some unknown combination than in the normal dog.
      These findings throw no definite light on the mechanism of the increased protein
      destruction characteristic of intestinal obstruction.

PMID- 19868968
TI  - EXPERIMENTS ON THE CULTIVATION OF THE ACTIVE AGENT OF MOSAIC DISEASE IN TOBACCO
      AND TOMATO PLANTS.
AB  - The results of the attempts here described to cultivate the incitant of mosaic
      disease of tobacco and tomato plants give good reason to suppose that this has
      been accomplished. The agent in the tissues of affected plants induces the
      disease not infrequently in a dilution of 1:10,000 but only very rarely at a
      higher dilution. During its transference from tube to tube of the special medium
      used in the present study it underwent a dilution far beyond these effective
      limits-in one experiment to 4 x 10(-16). Nevertheless, the material of the remote
      subplants proved effective in inducing the disease, which appeared as rapidly and
      in as active a form as if the undiluted inoculum had been employed. Material
      derived from plants in which mosaic developed as result of inoculation with the
      culture fluid induced the disease in yet other plants, and from these again the
      agent could be propagated in vitro, or transfers to other plants could be made.
      In the course of the experiments a significant fact was noted; namely, that the
      agent present in remote subplants which can induce the disease was not readily
      filterable. The nature of the change thus indicated remains to be determined. No
      formed elements could at any time be distinguished in the medium. The conclusion
      seems justified that the incitant of mosaic disease of tobacco and tomatoes is a
      living microbic body which can be cultivated in an artificial medium.

PMID- 19868969
TI  - SEROLOGICAL RELATIONSHIPS AMONG AND BETWEEN THE STREPTOCOCCI AND PNEUMOCOCCI.
AB  - Using the complement fixation reaction with whole bacterial solutions as
      antigens, it has been possible to confirm the existence, within the non-hemolytic
      streptococcus family, of two great groups. One of these groups, that which may be
      designated as of the left side, is related in an orderly way to the hemolytic
      streptococci; the other of the right side, is similarly related to the entire
      pneumococcus family. In addition, the hemolytic streptococcus family shows a
      reactive range which relates it, though less closely, to the non-hemolytic
      streptococci of the right side, and to the pneumococci. The existence of these
      cross-relationships is not associated with the precipitable substance of either
      family, but may tentatively be presumed to be dependent upon the properties of
      the protein or lipoid-protein fraction of the bacterial cell.

PMID- 19868970
TI  - CALCIUM AND PHOSPHORUS METABOLISM IN OSTEOMALACIA.
AB  - Osteomalacia is a diet deficiency disease of the same category as rickets. The
      deficiency is principally in the fat-soluble vitamine content of the diet, though
      there may be a calcium deficiency at the same time. The disease may be prevented
      by providing a diet rich in the fat-soluble vitamine content, and may be cured by
      adding the same to the diet.

PMID- 19868971
TI  - ON THE NATURE OF BACTERIAL ALLERGIES.
AB  - 1. There seems no further possibility of questioning the opinion that the
      development of tuberculin sensitiveness is definitely associated with the
      development of tissue reactions in the form of inflammatory processes; the mere
      development of antibodies on the injection of dissolved bacterial materials does
      not induce allergy. 2. Passive transfer of tuberculin allergy to guinea pigs may
      be accomplished by injections not only of the tissue extracts of the tuberculous
      foci of rabbits, but also of the sera of such rabbits, provided multiple, well
      developed, and not too advanced lesions are present in the rabbits furnishing
      them. The exact criteria by which such results can be regularly obtained have not
      yet been ascertained; our results in this respect, though definite, have been
      irregular and occasional. It is clear, moreover, that the capacity to convey such
      allergic hypersensitiveness has no relationship to the precipitating capacity of
      the serum for residue materials. 3. Just as the allergy-conveying power of the
      serum and its precipitating powers for residue are separable, so, also, the
      bacterial extracts representing the antigens for these reactions are separable,
      the residue material being particularly concerned in the specific precipitations
      with immune serum, the so called nucleoprotein being associated with allergic
      reactions in the tuberculous animals.

PMID- 19868972
TI  - ENCEPHALITOZOON CUNICULI AS A KIDNEY PARASITE IN THE RABBIT.
AB  - A spontaneous epidemic of nephritis among young rabbits associated with a
      protozoan parasite has been observed in a certain breeding stock since 1918. It
      is regarded as a nest infection. The parasite is tentatively classed among the
      microsporidia and the stages encountered are regarded as vegetative which may
      perhaps pass through several generations in the same host. It is a parasite of
      the epithelial cell, provoking no immediate host reactions. These are supposed to
      follow injury such as destruction of the epithelium and denudation and plugging
      of the tubules. The localizations in the brain are also without cell reaction,
      except under special conditions, and the many cell foci present are attributed to
      coccidia and perhaps bacteria and other intestinal parasites. The kidneys are
      looked upon as the normal habitat and the brain parasites as aberrant and outside
      the normal cycle unless it can be shown that the spores discharged into the
      circulation may again multiply in some organ like the kidneys in direct
      communication with the exterior. It is highly probable that many reported cases
      of nephritis among older rabbits used in experiments had their origin in an early
      invasion of the parasite described.

PMID- 19868973
TI  - THE RESPIRATORY RESPONSE TO CARBON DIOXIDE.
AB  - 1. A technique for determining the respiratory response to carbon dioxide on the
      Peabody principle is described. 2. The relation between minute volume of total
      pulmonary ventilation and percentage of carbon dioxide in the inspired air can be
      expressed by a simple mathematical formula, viz. Y = K + ab(z), in which Y is the
      ventilation rate, X is the CO(2) content of the inspired air, and K, a, and b are
      constants characteristic for the individual. 3. The respiratory response to
      carbon dioxide as expressed by the total pulmonary ventilation is slightly
      greater at high oxygen percentages (90 per cent +/-) than at normal oxygen
      percentages in the inspired air. 4. Respiratory fatigue may consist of two
      elements-one nervous, manifesting itself in increased excitability of the center
      and a more marked response when the demand for pulmonary ventilation is small,
      the other muscular and involving an inability to respond when the demand for
      pulmonary ventilation is great.

PMID- 19868974
TI  - THE SIGNIFICANCE OF ANAPHYLAXIS IN PNEUMOCOCCUS IMMUNITY.
AB  - 1. Intraperitoneal injections of killed and living broth cultures of a virulent
      pneumococcus produce in guinea pigs a high degree of active immunity and a serum
      with strong protective power. 2. Despite the protective power of such serum no
      agglutinins for the homologous organism and no precipitins for soluble
      derivatives were demonstrable. 3. Guinea pig immunity to pneumococcus infection
      produced by the method described is not attended by cutaneous allergy to
      derivatives of the pneumococcus used for immunization. 4. During the course of an
      artificially produced active immunity, anaphylaxis may at times be present and at
      times absent without any measurable effect upon the resistance of the animal to
      infection by intraperitoneal injection. 5. In the particular instance studied,
      the experiments indicate that anaphylaxis to pneumococcus protein has no
      important effect upon the resistance of the animal to infection. It appears to be
      a concomitant without any significant role in the immunity mechanism.

PMID- 19868975
TI  - THE PRODUCTION AND SIGNIFICANCE OF CUTANEOUS ALLERGY TO PNEUMOCOCCUS PROTEIN.
AB  - 1. Intracutaneous injection of guinea pigs with an alkaline extract of
      pneumococcus produces in about two-thirds of the animals an allergy with a skin
      reaction similar to the allergic skin response of tuberculosis. 2. Continuance of
      the intracutaneous injections after the appearance of allergy results in its
      disappearance. The skin ceases to react. 3. Neither the animals manifesting skin
      allergy nor those which fail to develop it show any significant alteration in
      susceptibility to pneumococcus infection by intraperitoneal inoculation.
      Similarly, animals desensitized by continuing the intracutaneous injections after
      the appearance of allergy show an unaltered susceptibility.

PMID- 19868976
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : I. IS THE LYTIC PRINCIPLE VOLATILE?
AB  - The lytic principle concerned in the phenomenon of transmissible lysis is not
      volatile. The results which have been taken to indicate volatility are, in our
      opinion, to be attributed to the transfer to the distillate of minute droplets of
      the original active filtrate.

PMID- 19868977
TI  - HYDROPIC STAGES IN THE INTESTINAL EPITHELIUM OF NEW-BORN CALVES.
AB  - There occurs in the small intestines of a large percentage of calves up to and
      including the 3rd day a hydropic condition of the epithelium. This manifests
      itself in the form of a large vacuole or vesicle usually under the top plate of
      the epithelial cell. More rarely a number of smaller vesicles or vacuoles replace
      it. These may break away from the cell and float free when bits of the fresh
      mucosa are gently compressed under a cover-glass. The vesicles probably contain
      coagulable protein. This condition has its origin in late intrauterine life. It
      involves the lowest third of the small intestine and extends upwards as far as
      the duodenum in some cases. It is not a necessary forerunner of the early
      diarrhea or scours. Its relation to this disease is not defined. It may or may
      not be accompanied by a fat stasis of the upper third of the small intestine.
      Frequently associated with it is coagulable protein in the contents of the ileum.

PMID- 19868978
TI  - THE BACTERIOLOGY OF THE INTESTINAL TRACT OF YOUNG CALVES WITH SPECIAL REFERENCE
      TO THE EARLY DIARRHEA ("SCOURS").
AB  - New-born calves receiving no colostrum, or else receiving it after some delay,
      may die of Bacillus coli septicemia, of which scours is a local manifestation.
      Calves receiving an insufficiently protective dose of colostrum may become
      victims of various bacterial diseases such as arthritis, nephritis, omphalitis,
      and possibly pneumonia. Calves receiving a sufficient dose of colostrum may still
      develop scours of various degrees of severity due to the local multiplication of
      various types of Bacillus coli in the small intestine. There exists in the young
      calf a delicate balance between certain strains of Bacillus coli and the mucous
      membrane and digestive ferments, which, upset in favor of Bacillus coli, produces
      scours. The necessary conditions for such attacks are in part inherited defects
      of the digestive tract, both morphological and functional, and special types of
      Bacillus coli, resident in the herd and environment. The immediate indications
      are a great increase in the number of Bacillus coli in the lowest third of the
      small intestine with a spreading of the invasion towards the duodenum as the
      disease gains headway. Under these conditions a general intoxication results. The
      bacilli form layers or films attached to the top plates of the epithelial cells.
      At this time morphological changes in the cells are not yet recognizable. The
      vacuolar or hydropic condition frequently found antedates the bacterial invasion
      and may be present in the absence of bacteria. In mild or recovered cases, during
      the 1st week a fatty infiltration of the epithelium is not infrequently present.
      In a large number of clinically normal calves, from 1 day to 3 months of age,
      Gram-negative bacilli were not present in sufficient numbers to be detected in
      sections, although enriched cultures, when attempted, revealed them.

PMID- 19868979
TI  - SKIN INFECTION OF RABBITS WITH HEMOLYTIC STREPTOCOCCI ISOLATED FROM A PATIENT
      WITH ERYSIPELAS : I. METHOD OF DEMONSTRATING PROTECTIVE ACTION OF IMMUNE SERA.
AB  - Cultures of a hemolytic streptococcus isolated from a human case of erysipelas
      were tested for ability to produce lesions by injecting various amounts
      intradermally in shaved rabbits. Severe lesions could be developed at will in
      this way despite the fact that intravenous or intraperitoneal inoculations of
      large doses of the cultures failed to kill. The lesions were of two sorts,
      phlegmonous and erysipelas-like. A serum capable of warding off the injurious
      action of the streptococcus on the skin was procured from animals receiving
      repeated intracutaneous inoculations of the organism. Normal serum by contrast
      had no protective effect. By intradermal injections at several points in the same
      normal rabbit of small quantities of mixtures of equal parts of serum and various
      dilutions of a suspension of streptococci it proved possible to test sera for the
      presence of substances protective against the streptococcus.

PMID- 19868980
TI  - LOCAL PASSIVE IMMUNITY IN THE SKIN OF RABBITS TO INFECTION WITH (1) A FILTERABLE
      VIRUS, AND (2) HEMOLYTIC STREPTOCOCCI.
AB  - Small areas of skin infiltrated with immune serum proved refractory to the
      injurious action of a filterable rabbit virus inoculated 24 to 48 hours later.
      Infiltrations of normal serum did not appreciably protect the skin against the
      virus. The local protection afforded by the infiltrations of immune serum appears
      to constitute an example of local passive immunity. Small areas of skin
      infiltrated with either normal serum or meat infusion broth proved more
      refractory than normal skin to infection with hemolytic streptococci inoculated
      24 hours later. The refractory state induced in the tissues was non-specific in
      character. A greater amount of local protection against hemolytic streptococci
      was afforded by infiltrations with a homologous immune serum than by
      infiltrations with normal serum. The difference in the amount of protection
      afforded by immune serum over that induced by normal serum may be thought of as
      representative of the degree of local passive immunity conferred.

PMID- 19868981
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : VI. THE RELATIVE SUSCEPTIBILITY OF DIFFERENT STRAINS OF MICE TO
      PER Os INFECTION WITH THE TYPE II BACILLUS OF MOUSE TYPHOID (BACILLUS PESTIS
      CAVIAE).
AB  - Five separate strains of mice have been tested for their relative susceptibility
      to per os infection with the Type II bacillus of mouse typhoid (Bacillus pestis
      caviae), more than 500 individuals of each strain having been employed in the
      course of 12 months. Clear-cut differences in the susceptibility of these strains
      to the infection have been shown to exist.

PMID- 19868982
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : VII. SEASONAL VARIATION IN THE SUSCEPTIBILITY OF DIFFERENT
      STRAINS OF MICE TO PER Os INFECTION WITH THE TYPE II BACILLUS OF MOUSE TYPHOID
      (BACILLUS PESTIS CAVIAE).
AB  - Seasonal variations are described in the response of five strains of mice to
      inoculation with the Type II bacillus of mouse typhoid (Bacillus pestis caviae).
      There occurred in the case of all strains a high peak of mortality during the
      spring, a lower death rate during the summer, and a subsequent autumn rise in the
      number of deaths.

PMID- 19868983
TI  - CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS : I. AN EXOTIC
      STRAIN OF ENCEPHALITOGENIC VIRUS.
AB  - In this paper is given an account of an inoculable virus disease produced in the
      rabbit with cerebrospinal fluid taken from a case of vascular and neural
      syphilis. The study which yielded the results presented was undertaken in the
      course of an investigation into the etiology of epidemic or lethargic
      encephalitis. Twenty-seven samples of cerebrospinal fluid, derived from cases of
      epidemic encephalitis, were tested by us upon rabbits without positive result.
      The one successful instance in which an inoculable disease was produced arose
      from the injection of one of three specimens of the cerebrospinal fluid taken
      from the case of syphilis. Following this success, two subsequent injections of
      the fluid, taken from the same patient, were made unsuccessfully. Although
      certain American and European investigators have reported securing a virus from
      the cerebrospinal fluid of cases of epidemic encephalitis, we have consistently
      failed in our endeavors to confirm their results. However, we believe that the
      finding of the J. B. virus may serve to clarify the obscurity and confusion now
      enveloping the so called virus of encephalitis. It had previously been shown that
      no biological differences could be detected between the herpes and the
      encephalitis strains of virus. The former, as is well known, is readily secured
      by inoculating rabbits with the contents of herpes vesicles, while the latter
      has, at best, been obtained with great difficulty. The J. B. virus agrees
      biologically with the herpes and encephalitis strains of virus. It is our opinion
      that the J. B. virus is merely a herpes virus which has gained access to the
      cerebrospinal fluid and, at the time of inoculation of the rabbits, was present
      in a concentration sufficing to induce virus encephalitis. The fact, if fact it
      is proved to be, that the herpes virus may find its way into the cerebrospinal
      fluid opens to question all the supposed instances of successful implantation of
      a virus of epidemic encephalitis upon the rabbit. It is indeed highly probable
      that, in so far as such a virus has been found at all in the cerebrospinal fluid,
      it also is a specimen of the herpes virus. Our studies lead us to suppose that at
      best it is an infrequent event for the herpes virus to occur in demonstrable form
      in the cerebrospinal fluid. Perhaps a more delicate means of detection than the
      rabbit inoculation would serve to reveal the presence oftener. It is known that
      strains of herpes virus of greater or less intensity of action for rabbits exist.
      It is, of course, possible that we discover, by present methods, only the highly
      active strains and those only when chancing to be present in a certain
      concentration. We inoculated 100 specimens of cerebrospinal fluid and obtained in
      a single instance the virus infection of the rabbit. In all respects the J. B.
      virus agrees in intensity of effect, in mode of attack upon the cornea, skin, and
      brain, and in immunization responses, with the true strains of herpes virus and
      the so called strains of encephalitis virus. If, as the above statements
      indicate, all the virus strains of the class considered are examples of the
      herpes virus, it follows that the etiology of epidemic encephalitis remains
      entirely unresolved. It is highly improbable that the ubiquitous herpes virus
      plays the kind of part in human pathology which it has been shown to play in
      experimental rabbit pathology. While the active strains of that virus possess a
      strong affinity for the brain structures of the rabbit, the virus has not in the
      past shown any selective affinity for the brain of man. To ascribe epidemic
      encephalitis in man to particular and peculiar varieties of the herpes virus is,
      with our present knowledge, unwarranted.(20) The wide variations in histological
      lesions described in the brain of rabbits succumbing to herpes or virus
      encephalitis raise the question of the essential manner of action of the virus
      upon the brain tissues. Hitherto it has been the cellular infiltrative lesions
      which have been emphasized. We have, however, learned that very extensive
      infiltrations about blood vessels and in the brain substance may exist
      independently of even mild symptoms of disease.(16) The question is propounded,
      therefore, whether the herpes virus does not attack nerve cells directly,
      affecting them quantitatively in such ways as at one time to produce stimulation
      and at another time paralysis. The manifold symptoms of virus encephalitis in the
      rabbit are open to this interpretation. In order, however, to base this notion on
      microscopical findings, a more subtle technique than hitherto widely employed is
      required. A histological restudy of the subject is being made with this view in
      mind. The name virus encephalitis is proposed for the experimental disease
      produced in rabbits by the inoculation of the herpes and allied viruses.

PMID- 19868984
TI  - CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS : II. HERPETIC
      STRAINS OF ENCEPHALITOGENIC VIRUS.
AB  - In this paper we have sought to show that unequivocal strains of herpes virus
      exist in man, which, in the rabbit, exhibit a degree of encephalitogenic power
      not exceeded, and perhaps rarely equalled, by any strain of the so called
      encephalitis virus. The fact that such highly encephalitogenic strains of the
      herpes virus exist in nature has, at the moment, theoretical and practical
      importance. Until recently, the view has been accepted by certain workers in the
      field that two biologically distinct viruses of this class occur-one inducing
      epidemic encephalitis and the other febrile herpes in man. This view, is, indeed,
      being supplanted at the present time by the notion, advocated by Levaditi,
      Nicolau, and Poincloux, of a group of closely related virus organisms for which
      the name "herpetico-encephalitic" is proposed. Within this group they distinguish
      strains of virus displaying special affinities for the central nervous organs and
      others exhibiting equal affinities for skin and membrane (cornea) structures. The
      first mentioned strains are responsible, under suitable circumstances, for
      epidemics of encephalitis in man; the others give rise to ordinary attacks of
      febrile herpes. The H. F. virus described in this paper does not conform to the
      classification indicated. While being a true febrile herpes strain, it possesses,
      nevertheless) a high degree of power to attack the central nervous system as well
      as marked capacity to implant itself on the skin and the cornea of the rabbit.
      Not only does virus encephalitis follow invariably upon the intracranial
      injection of the H. F. virus, but as regularly upon corneal, skin, nasal, blood,
      and testicular modes of inoculation. The symptoms of virus encephalitis thus
      provoked and the character of the brain lesions induced are precisely those, in
      all their detail and variety, including the presence of intracellular inclusion
      bodies, which have been described for the so called virus of encephalitis.
      Moreover, the H. F. virus is durably glycerol-resistant, is filterable through
      Berkefeld candles, and behaves immunologically as do the usual strains of herpes
      and of encephalitis virus. On the basis of the experimental data presented, we
      conclude that any distinction made regarding, on the one hand, encephalitogenic
      power as a special property of a virus secured from cases of epidemic
      encephalitis, and, on the other hand, of ectotropic action as an equally special
      quality of a virus yielded by febrile herpes, is in its nature artificial and not
      in harmony with ascertained fact. What can, indeed, be distinguished are stronger
      and weaker strains of a virus) probably always herpetic in origin, as determined
      by the inoculation of rabbits. While a strong herpes virus is both dermatotropic
      and neurotropic, a weak virus tends, in its multiplication, to remain confined to
      the site of inoculation, to act chiefly on the tissues on which it is immediately
      implanted, and not to extend to distant parts. And this is equally true whether
      the strain of virus came originally from cases of epidemic encephalitis, or
      merely from cases of febrile herpes in man. Hence direct comparison cannot be
      made between the stronger encephalitogenic and weaker non-encephalitogenic
      strains, according to any specific etiological property. The viruses we are
      discussing do, indeed, compose one group but it is the group of febrile herpes
      with which epidemic encephalitis is associated accidentally, if at all. It
      happens, indeed, that the Levaditi strain (souche) C and the Doerr Basel strain,
      both supposedly originating in cases of encephalitis in man, are less
      encephalitogenic for the rabbit than the true herpes strains, H. F. and
      Goodpasture M.

PMID- 19868985
TI  - A COMPARISON OF THE EFFECTS OF X-RAY AND DRY HEAT ON ANTIBODY FORMATION.
AB  - Rabbits x-rayed in doses sufficient to reduce the amount of their lymphoid tissue
      without damage to the bone marrow showed a definite deficiency in the production
      of precipitins, bacterial agglutinins, and protective antibodies. On the other
      hand, rabbits subjected to exposures of dry heat sufficient to increase the
      activity of the lymphoid organs, on immunization develop antibodies in larger
      quantity than do untreated animals immunized by the same process.

PMID- 19868986
TI  - THE INFLUENCE OF THE "DIAPLYTE" ANTIGEN OF DREYER ON TUBERCULOSIS OF THE GUINEA
      PIG.
AB  - We have prepared "diaplyte" antigen according to Dreyer's procedure and have
      studied its therapeutic and prophylactic value in experimental tuberculosis of
      guinea pigs. In our hands it has failed to yield beneficial effects. The animals
      treated with the antigen tended in general to develop lesions more quickly and to
      die earlier than the controls.

PMID- 19868987
TI  - EPIDEMIOLOGICAL STUDIES ON RESPIRATORY INFECTIONS OF THE RABBIT : VI. ETIOLOGY OF
      OTITIS MEDIA.
AB  - A common form of otitis media occurring in rabbits is described. The condition in
      the great majority of instances is associated with the inflammation of the upper
      respiratory tract known as snuffles and with the presence of Bacterium
      lepisepticum. This organism, when introduced into the external nares of rabbits
      hitherto protected from infection with it, is capable of inducing a purulent
      otitis media indistinguishable from the natural one. In the rabbit the connection
      between the nasal passages and the middle ear is such that a pathogenic agent
      introduced into the nose may readily invade the entire group of cavities
      connected with the upper respiratory tract.

PMID- 19868988
TI  - STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS : VIII. NATURE OF THE
      OXIDATION-REDUCTION SYSTEMS IN STERILE PNEUMOCOCCUS EXTRACTS.
AB  - 1. The systems responsible for oxidation and reduction in the pneumococcus cell
      have been shown to consist of two components, the nature of which has been
      discussed. 2. The oxidizing and reducing power of active extracts of pneumococci
      is inactivated by exposure to air. This loss in activity is due to an
      inactivation of the thermolabile cellular component consequent on secondary
      reactions analogous to those which under similar conditions destroy the hemotoxin
      and enzymes in pneumococcus extracts.

PMID- 19868989
TI  - STUDIES ON THE OXIDATION-REDUCTION OF HEMOGLOBIN AND METHEMOGLOBIN : I. THE
      CHANGES INDUCED BY PNEUMOCOCCI AND BY STERILE ANIMAL TISSUE.
AB  - The Pneumococcus is capable of oxidizing hemoglobin to methemoglobin and of
      reducing the latter to hemoglobin again. Both the living organism and sterile
      extracts will accomplish the changes; and like systems seem to be involved in
      them. The type of reaction induced is determined by the presence or absence of
      molecular oxygen. The oxidation and reduction of the blood pigments are
      reversible processes. The equilibrium between hemoglobin and methemoglobin in a
      mixture of blood and pneumococcus cellular substances may be shifted in either
      direction at will by regulation of the oxygen tension. In the present paper
      quantitative evidence is presented of the reduction of methemoglobin to
      hemoglobin by sterile animal tissues. The possible relations of this activity to
      the disappearance of methemoglobin from the blood stream of the living animal are
      discussed.

PMID- 19868990
TI  - THE BICARBONATE RESERVE AND THE DISSOCIATION CURVE OF OXYHEMOGLOBIN IN FEBRILE
      CONDITIONS.
AB  - From Fig. 1 it may be seen that the effect of elevated temperature during the
      pyrexial period upon 1/K and therefore on the dissociation curve of oxyhemoglobin
      was, on the average, greater than would have been expected from experiments on
      normal blood in vitro, and greater than would be expected in view of the
      alkalosis occurring See PDF for Structure during fever. Temperature rise, and
      excess hydroxyl ion acting in vitro in the opposite directions, seemed to
      indicate a more stable state of affairs than was found. Apparently other factors
      have come into play, as, for example, alterations in the proportions and
      concentrations of the various electrolytes. In pneumonia, for instance, there is
      a retention of chloride during the febrile period with excessive loss of
      phosphates. The variations were not due to variations in the hemoglobin molecule
      itself since from the work of Adair, Barcroft, and Bock (18) hemoglobin must
      apparently be reckoned as having identical properties in normal individuals of
      the same species. If Barcroft's (19) hypothesis be right, namely that the C(H)
      within the corpuscle is higher than that of the plasma, the observed variations
      of 1/K may not be so surprising. In view of the fact that the hemoglobin inside
      the corpuscle is enclosed within a semipermeable membrane, the possibility arises
      of the setting up of membrane equilibria which will protect the respiratory
      pigment from excessive changes of reaction that may occur in the plasma, and thus
      the optimum conditions for the carriage of oxygen to the tissues may be
      maintained. Krogh and Leitch (10) in 1919 also drew attention to the protected
      situation of hemoglobin inside the corpuscle. In Case 6 it seems as if the
      alkalosis consequent on the febrile state had gained the upper hand and had
      extinguished the normal temperature reaction. This is rather confirmed by the
      fact that clinically the case showed one of the earlier signs of an alkalosis;
      namely, twitching of the facial muscles. Case 10, who had been on salicylate,
      also showed an analogous effect, when 6 days after the first observation the
      temperature shift was practically nil. The relationship between pH, 1/K, and the
      febrile temperature still awaits investigation. The extent of the shift of the
      dissociation curve was not by any means uniform; in neither Fig. 1 nor Fig. 2 is
      the highest value of 1/K at the highest temperature recorded. Fig. 2 shows the
      effect of temperature rise upon 1/K after cessation of the pyrexia; the effect is
      not so marked. Some cases, however, showed a variation in excess of the normal as
      if there was not yet complete return to normal. See PDF for Structure
      Biologically these changes are of importance in that this shifting of the
      dissociation curve to the right in fever means that there is more oxygen
      available for the tissues than normally, more especially at higher pressures. The
      tension of unloading is raised. This, in addition to the accelerated circulation
      and the probable increased velocity o[ reaction, means that even in a localized
      area of inflammation, if there is increased temperature, the tissues are placed
      in a better position for resisting infection as a result of their better
      oxygenation. That there is increased metabolism during fever has been
      conclusively shown by Du Bois (20) and others using large bed calorimeters. Du
      Bois has shown that the increase in metabolism obeys van't Hoff's law, increasing
      13 per cent for each 1 degrees C. rise. This shifting of the curve then falls
      into line with these observations as an adaptive response to the febrile
      condition, and the febrile temperature, if not too great, would seem to be a
      purposive attempt to aid the combating of infection. This shifting of the curve
      probably explains Uyeno's (21) observation on the effect of increased temperature
      on the circulation in the cat; namely, increased coefficient of utilization, and
      increased fall in the saturation of the mixed venous blood. Turning now to Table
      II, we find that, if the CO(2) dissociation curve of Haldane (12) is accepted as
      normal, the bicarbonate reserve of five of the cases was above normal, of one
      normal, and of the rest below normal. Gastric secretion was not the cause of the
      varying curves, since the time of drawing the blood in all cases was during
      intestinal digestion. No observations having been made on the blood pH or the
      alveolar CO(2), we cannot be absolutely certain as to the actual reactions, more
      especially in the last cases; Case 6, however, was probably one showing a
      partially compensated CO(2) deficit in view of the absolute lowering of the total
      bicarbonate and evidence clinically of a tendency to alkalosis. Case 3, which had
      a lowered reserve, was probably similar. Koehler (22) gives a series of blood pH
      determinations in acute fevers in which ten out of twelve cases showed an
      uncompensated alkalosis when the temperature was 103 degrees F. (39.4 degrees C.)
      or over. Pemberton and Crouter (23) in a study on the response to the therapeutic
      application of external heat also observed a tendency for the reaction to shift
      to the alkaline side as shown by the alteration in the pH of the sweat. Hill and
      Flack (24) and Bazett and Haldane (25) observed that in thermal fever there was
      an excessive loss of CO(2) comparable to the effect of hyperpnea. These facts are
      of importance in view of the above results regarding the bicarbonate reserve.
      That there was a definite alkalosis in some of the cases is at least shown by the
      value of 1/K at 37.0 degrees C. during the pyrexial period in Cases 1, 2, and 7.
      The upper limits of 1/K at 37.0 degrees C. both during pyrexia and after were
      similar. Of other factors that might be considered, reference may be made to the
      work of Barbour and his associates (26-29), who showed that in hyperthermia and
      fever there is an alteration in the concentration of the blood. But the changes
      were hardly of such magnitude as to cause the variations above detailed.

PMID- 19868991
TI  - ALLERGIC IRRITABILITY : II. ANAPHYLAXIS IN THE GUINEA PIG AS AFFECTED BY THE
      INHERITANCE.
AB  - Inbred lines of guinea pig which have previously been observed to differ in their
      susceptibility to tuberculosis differ in their anaphylactic responses as well.
      The families that are relatively resistant to tuberculosis appear also to be
      somewhat more resistant to some one or more of the phases of the anaphylactic
      reaction complex.

PMID- 19868992
TI  - A PURE STRAIN OF THYROID CELLS AND ITS CHARACTERISTICS.
AB  - 1. A pure strain of thyroid epithelium was isolated and maintained in active
      condition for 7 months. At the end of the experiment, the rate of cell
      multiplication was as great as at its beginning. 2. The thyroid cells grew at the
      surface of the coagulum as pavement epithelium, and within the coagulum as a
      glandular structure. 3. The cells did not dedifferentiate, and the lumen of the
      acini in cultures from a strain over 4 months old contained colloid secretion
      similar morphologically to that from a freshly extirpated thyroid gland.

PMID- 19868993
TI  - RESISTANCE TO SPONTANEOUS MOUSE CANCER INDUCED BY INJECTIONS OF OLEIC ACID.
AB  - The experiments reported here show that the resistance of mice to spontaneous
      neoplastic diseases can be increased by means of oleic acid injections. This is
      demonstrated (1) by the greatly reduced incidence of local recurrences at the
      site of operation, and the lessened incidence (2) of primary tumors developing at
      other locations, (3) of metastases as encountered at autopsy, and (4) of takes of
      autoplastic tumor grafts, while finally, (5) there is an appreciable increase of
      the average postoperative longevity. Supplementary to the above results is the
      finding that in the treated mice the reaction about the implanted cancer graft
      differs from that encountered in untreated animals.

PMID- 19868994
TI  - CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS : III.
      VARIETIES AND PROPERTIES OF THE HERPES VIRUS.
AB  - Mild strains of the virus of herpes are described the action of which tends to be
      confined and local. Unless, therefore, these mild strains are injected
      intracranially they do not tend to produce virus encephalitis in the rabbit.
      Recovery from infection with the mild strains confers immunity to virulent
      strains of the herpes and allied viruses. Long glycerolation reduces the number
      of viable organisms. This loss among the mild strains may reduce the virus below
      the strength required for an effective extracranial although not below the
      strength needed for an intracranial inoculation. Herpes virus carriage in man,
      even under highly favorable conditions, is difficult of detection by means of
      rabbit inoculation. The detection may be achieved by intracranial when it cannot
      be accomplished by intracorneal inoculation. The virus producing encephalitis in
      the rabbit attaches itself chiefly to and multiplies in the substance of the
      central nervous system. Hence its detection in the cerebrospinal fluid is rarely
      accomplished. When the inoculation of the virus is made intracranially and
      especially when the inoculum is composed of active brain tissue, the virus is
      discoverable in the cerebrospinal fluid by rabbit inoculation much more
      frequently than when the virus encephalitis follows an extracranial variety of
      infection. The herpes virus is capable of excretion by the kidney of the rabbit
      and of being detected in the urine by rabbit inoculation. Among the rarer
      symptoms of virus encephalitis is excessive lacrimation. While salivation is
      frequent, lacrimation is exceptional. A comparison of the Levaditi, Doerr, and
      Goodpasture strains of virus indicates the first to be of medium, the second of
      mild, and the third of high degree of neurotropic activity. The Doerr strain
      resembles the mild herpes strains described in this paper. The Goodpasture virus,
      while exceeding the Levaditi strain in affinity for the central nervous system,
      falls below the H. F. strain in this regard. Neutralization of virus by the serum
      of infected and recovered rabbits takes place regularly within certain
      quantitative limits. Neutralization with human serum is inconstant and capricious
      and without demonstrable relation to previous attacks of epidemic encephalitis.
      Comparison of the clinical types of encephalitis as presented by the epidemic
      variety in man and the experimental virus variety in rabbits brings out certain
      correspondences and certain differences. It is only in partial and essentially
      superficial aspects that the two diseases can be identified one with the other.

PMID- 19868995
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : I. GENERAL FEATURES OF
      VITAL STAINING WITH LITMUS.
AB  - The present paper is the first of a series of reports on the relative reaction of
      living tissues as determined by vital staining with indicators. It is possible to
      bring about a localized and a general coloration of living rats and mice with
      litmus. The animals remain in good health and the coloration of some of the
      tissues persists for months. Much of the dye is stored in cell granules,
      especially in those of the reticulo-endothelial elements, but a diffuse staining
      of certain tissues occurs, notably of bone, epidermis, cartilage, and connective
      tissue everywhere. In the intensity and localization of the bony coloration
      litmus has resemblances to madder. Diffuse staining with it renders blue most, if
      not all, of the tissues affected, while a granular staining causes others to
      become notably pink, owing to the fact that the indicator, though introduced into
      the organism in the blue form and circulating as such in the body fluids, is
      ordinarily red when stored in cells. The polymorphonuclear elements and
      macrophages of a peritoneal exudate, may become so laden with material colored
      red by litmus that the blue color of the fluid constituent is masked and the
      exudate appears a deep, turbid red. The phenomenon is but one manifestation of a
      notable acidity within cell granules throughout the organism. Like many another
      in the stained animals it would appear to be of physiological import. Some of the
      questions suggested by the work will be dealt with in the paper immediately
      following.

PMID- 19868996
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN-TISSUES : II. ON THE MOBILIZATION
      OF ACID MATERIAL WITHIN CELLS, AND THE REACTION AS INFLUENCED BY THE CELL STATE.
AB  - The acidity of the macrophage granules in which litmus comes to be stored during
      life is considerable. It has proved possible to stain these granules in vivo with
      some of the phthalein indicators and the results, had they been obtained under
      controlled conditions, would indicate a pH of 3.0 or less. The amount of acid
      material which may accumulate within the cells of animals stained with litmus is
      great, sufficient in the case of the elements of a peritoneal exudate for the
      acid reaction to prevail when they are gathered together and crushed. The
      material is derived, not from the dye, but from living elements responding
      characteristically to a stimulus far from unique. Such responses may well play a
      role in normal physiological activities and in the cellular defense against
      microorganisms. Vital staining with litmus demonstrates anew that the
      intracellular reaction during life is independent of that of the body fluids. By
      means of color changes in the stored indicator one can distinguish sick as well
      as dead cells of certain sorts and follow their distribution and fate within the
      organism. There are data to suggest that with the aid of the indicator the normal
      period of survival of certain elements at least can be determined. By the
      indicator method, of which the foregoing observations afford a crude
      illustration, much should be learnt in the future about body processes. The
      present paper is the second of a series upon the theme.

PMID- 19868997
TI  - FOCAL INTERSTITIAL NEPHRITIS IN THE CALF FOLLOWING INTERFERENCE WITH THE NORMAL
      INTAKE OF COLOSTRUM.
AB  - An interstitial focal nephritis found in young calves during the 1st or later
      months of life, associated with or preceded by the invasion of a special,
      virulent type of Bacillus coli, may be produced by postponing the feeding of
      colostrum 24 to 36 hours, or by withholding it altogether. In the presence of a
      virulent type of Bacillus coli few calves completely deprived of colostrum
      survive the 1st week. Among the survivors, the spotted kidney, the result of
      Bacillus coli bacteriemia, is frequently encountered. Calves normally fed have
      not shown the spotted kidney, and such as have been killed early have had
      uniformly sterile kidneys.

PMID- 19868998
TI  - ON THE ANTIGENS OF RED BLOOD CORPUSCLES : THE QUESTION OF LIPOID ANTIGENS.
AB  - Erythrocytes contain more than one substance responsible for the production of
      lysins and agglutinins. By injections of alcoholic extracts of horse erythrocytes
      mixed with a foreign serum, hemolysins and agglutinins can be more readily
      obtained than by the same quantities of extract alone. The immune sera reacted on
      horse and donkey blood but not on the blood of other species. The antibodies
      obtained differ from those prepared in the usual way with unchanged red blood
      corpuscles. The differences involve the ratio lysin: agglutinin, the specificity,
      the inhibition of hemolysis by alcoholic extracts, and the flocculation of these
      extracts. Ordinary anti-horse sera give flocculation reactions with emulsions of
      alcoholic extracts of corpuscles but to a lesser degree and not so regularly as
      those produced by means of extracts. The specific substances present in alcoholic
      blood extracts are probably not proteins. According to this view, species
      specificity in animals depends not alone on proteins but also on another group of
      substances.

PMID- 19868999
TI  - ON BIMOLECULAR LAYERS OF LIPOIDS ON THE CHROMOCYTES OF THE BLOOD.
AB  - We have examined the blood of man and of the rabbit, dog, guinea pig, sheep, and
      goat. There exists a great difference in the size of the red blood cells of these
      animals, but the total surfaces of the chromocytes See PDF for Structure from 0.1
      cc. blood do not show a similarly great divergence, because animals having very
      small cells (goat and sheep) have much greater quantities of these cells in their
      blood than animals with blood cells of larger dimensions (dog and rabbit). We
      give all the results of our experiments, omitting only those in which we were
      unable to avoid losses in the procedure of evaporation of the acetone. It is
      clear that all our results fit in well with the supposition that the chromocytes
      are covered by a layer of fatty substances that is two molecules thick.

PMID- 19869000
TI  - THE INFLUENCE OF A LOW ELECTROMOTIVE FORCE ON THE ELECTROPHORESIS OF LYMPHOCYTES
      OF DIFFERENT AGES.
AB  - 1. Small lymphocytes in serum at 37 degrees C. migrate toward the anode under
      experimental conditions described. 2. The electromotive force of 0.8 volt per cm.
      under the same conditions produced a straight line velocity which approximated
      that reported by McCutcheon for spontaneous velocity after his preparation had
      been studied over 5 hours. 3. Keeping the lymphocytes on ice up to 30 hours did
      not produce an appreciable difference in velocity of straight line migration from
      that speed determined if the cells were studied immediately. 4. The possible
      relationships between the type and order of magnitude of the electromotive force
      passing between injured and normal tissues and the electromotive force used
      experimentally are briefly discussed.

PMID- 19869001
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : III. INDICATED
      DIFFERENCES IN THE REACTION OF THE BLOOD AND TISSUES ON VITAL STAINING WITH
      PHTHALEINS.
AB  - Mice can be vitally stained with many of the phthalein indicators. The staining
      is diffuse, appearing to interfere not at all with health in the case of the
      majority of the dyes. The color phenomena show that these retain the character of
      indicators. A special technique has been evolved for the determination of the
      hues of the various organs, which are readily modified by extraneous influences.
      The ability to recognize that the pH has thus been altered is a signal advantage
      of the indicator method. Phthaleins of slightly alkaline range or one that
      trenches slightly on acidity have been employed for the work here reported.
      Cresol red, phenol red, and brom phenol red have proved especially useful. The
      observations with the three agree closely in pointing to the existence of notable
      differences between the reaction of the blood and that within the tissues
      generally. The hue of blood plasma from the right heart is such as to suggest
      that its reaction lies at about pH 7.38 ordinarily, whereas that of the most
      alkaline of the tissues, judging from its color, the connective tissue, would
      appear to have a pH of 7.2 or slightly less. The tendons seem to be nearly but
      not quite so alkaline. The other stained tissues without exception, are of a hue
      which would indicate that the reaction lies beyond the range of phenol red on the
      acid side, that is to say is at least as acid as pH 6.6. In a subsequent paper
      observations which accord with these findings, carried out with indicators of
      frankly acid range, will be described. On the exposure of tissues to air, without
      disturbance of the circulation, some of them become alkaline. In the case of
      connective tissue, at least, the change is a consequence of the escape of carbon
      dioxide. The gas passes readily in and out, exerting a practically immediate
      influence on the color of the tissue bared by eversion of a skin flap; and so
      much may be absorbed on exposure to pure carbon dioxide, when the surface is
      large, that a general acidosis results. The precise interpretation of the color
      changes in terms of pH waits necessarily upon further work.

PMID- 19869002
TI  - RESISTANCE OF BACTERIAL SPORES TO THE TRIPHENYLMETHANE DYES.
AB  - 1. Bacterial spores are highly resistant to the bactericidal action of the
      triphenylmethane dyes. Many Bacillus anthracis and Bacillus subtilis spores
      resist a saturated aqueous solution of gentian violet for 24 hours at 37 degrees
      C. They also resist exposure to the same dye solution for 10 minutes at 80
      degrees C. 2. The selective bactericidal action of these dyes applies only to the
      vegetative cells. Spores of the Gram-positive bacteria are more resistant to
      these dyes than the vegetative cells of Gram-negative bacteria. 3. The vegetative
      cells of Bacillus anthracis show variation in resistance to the bacteriostatic
      action of gentian violet. The spores of Bacillus anthracis show variation in
      resistance to the bactericidal action of gentian violet. 4. Bacillus anthracis
      can increase in resistance to the bacteriostatic action of gentian violet and
      grow in dye dilutions inhibiting the original culture. There is the possibility
      of pathogenic organisms becoming dye-resistant in the body when exposed to non
      bactericidal concentrations. For this reason it is advisable to use the greatest
      concentration of dye compatible with tissue tolerance. 5. Since the spores of
      pathogenic bacteria may lie dormant for longer periods than the dyes retain their
      bacteriostatic action in the body frequent applications of the dye should be made
      in preventing infections by spore-bearing bacteria.

PMID- 19869003
TI  - STUDIES IN EXPERIMENTAL SYPHILIS : I. THE INFLUENCE OF THE SIZE OF INOCULUM ON
      THE COURSE OF EXPERIMENTAL SYPHILIS IN THE RABBIT.
AB  - 1. The size of the dose of the infecting material exerts an appreciable effect
      upon the duration of the incubation period in experimental syphilis of the
      rabbit. Other things being equal, the larger the dose the shorter is the
      incubation period. 2. The size of the inoculum was not found to exercise any
      marked effect upon the course of the disease as a whole. 3. In individual rabbits
      inoculated with minimal amounts of virus the disease may run a malignant course.

PMID- 19869004
TI  - STUDIES IN EXPERIMENTAL SYPHILIS : II. THE INFLUENCE OF A NON-SPECIFIC
      INFLAMMATORY REACTION UPON THE DEVELOPMENT OF THE CHANCRE.
AB  - Rabbits can be successfully infected with syphilis by the inoculation of surface
      wounds with virulent strains of Treponema pallidum. Old granulating wounds in
      these animals constitute a particularly favorable terrain for syphilis
      inoculation, the chancre developing relatively soon and attaining a greater size
      than the lesion occurring on the basis of a fresh wound. Coal tar dermatitis
      renders the skin susceptible to infection with Treponema pallidum. The possible
      reasons for these phenomena are discussed and an hypothesis to account for them
      is advanced.

PMID- 19869005
TI  - STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY : I. THE QUANTITATIVE DETERMINATION
      OF UROBILIN.
AB  - Methods are presented for the development of clear fluorescent solutions from
      urobilin-containing urine, feces, and bile obtained from the dog. Conversion of
      the urobilinogen to urobilin is accomplished during the procedures. Measurement
      of the urobilin content is effected by comparing its fluorescence at great
      dilution with a standard containing acriflavine, calibrated in turn against pure
      urobilin. Means have been found to avoid the influence of the factors responsible
      in part for the inaccuracy of urobilin determinations. The method will quantitate
      exceedingly small amounts of urobilin and estimations on the same material agree
      within 10 per cent. Though designed for experimental procedures on the dog, the
      methods would seem adapted for clinical uses as well.

PMID- 19869006
TI  - STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY : II. DERIVATION OF UROBILIN.
      RELATION OF THE BILE TO THE PRESENCE OF UROBILIN IN THE BODY.
AB  - Methods have been developed whereby animals can be totally, partially, and
      intermittently deprived of their bile, without infection of this secretion or of
      the duct system. In all the instances considered the bile remained sterile
      throughout the period of the experiment. With this aid we have studied urobilin
      physiology. We have been able to show that the normal presence of urobilin in the
      bile and feces of dogs depends on the passage of bile pigment to the intestine,
      either through the normal channels, or by abnormal ones, as when it is fed by
      mouth. Complete loss of the bile from the body resulted in the total
      disappearance of urobilin and urobilinogen from the bile, feces, and urine.
      Rarely very faint traces remained in the feces, the origin of which has been
      discussed. Partial loss of the bile resulted in a corresponding reduction in the
      urobilin of the dejecta. Feedings of sterile urobilin-free dog bile to intubated
      dogs losing all of their bile and having no urobilin in it, or in feces or urine,
      were followed by the appearance of the pigment in the hepatic bile secreted
      shortly thereafter. When the feedings were stopped the urobilin soon disappeared.
      Total obstruction of the bile flow caused disappearance of the urobilin of the
      bile and stool. Later as the animals became heavily jaundiced the pigment
      appeared again in very small quantity in the feces. Autopsy at this time showed
      that the intestinal mucosa was deeply tinted with bilirubin some of which
      undoubtedly had passed into the lumen of the bowel and had there been changed to
      urobilin. Employment of the "altercursive intubation," by which an intermittent
      diversion of the bile stream of animals from the intestine to a collecting
      apparatus could be effected, showed that while bile pigment still reached the
      intestine urobilin was present in the bile secreted by the liver but that almost
      at once after the bile had been diverted from the gut urobilin disappeared from
      it. In relation to this finding it was noticed that in animals from which merely
      a small fraction of the bile was collected, that from a single liver lobe, while
      the greater portion reached the intestine there was most urobilin in the bile at
      times when most bilirubin was entering the intestine.

PMID- 19869007
TI  - STUDIES ON THE OXIDATION-REDUCTION OF HEMOGLOBIN AND METHEMOGLOBIN : II. THE
      OXIDATION OF HEMOGLOBIN AND REDUCTION OF METHEMOGLOBIN BY ANAEROBIC BACILLI AND
      BY STERILE PLANT TISSUE.
AB  - The oxidation-reduction systems of anaerobic bacteria manifest their action upon
      the blood pigments by marked deoxygenation of oxyhemoglobin, prompt reduction of
      methemoglobin to hemoglobin, and to a less marked degree oxidation of hemoglobin
      to methemoglobin. The action of sterile plant tissue upon oxyhemoglobin,
      hemoglobin, and methemoglobin has been studied. The oxidations and reductions of
      the blood pigments which are induced by sterile plant tissue are similar to the
      reactions which are brought about by pneumococci and by anaerobic bacteria.

PMID- 19869008
TI  - STUDIES ON THE OXIDATION-REDUCTION OF HEMOGLOBIN AND METHEMOGLOBIN : III. THE
      FORMATION OF METHEMOGLOBIN DURING THE OXIDATION OF AUTOXIDIZABLE SUBSTANCES.
AB  - Hemoglobin is oxidized to methemoglobin by products formed during the oxidation
      of a number of different substances. With some of these substances, both oxygen
      consumption and hemoglobin oxidation are accelerated by thermolabile constituents
      of pneumococci; with others of the easily oxidized substances, neither reaction
      seems to be influenced by the presence of the bacterial substances. The same
      substances which in the presence of air induce the oxidation of hemoglobin bring
      about the reverse reaction if molecular oxygen is excluded.

PMID- 19869009
TI  - STUDIES ON THE OXIDATION-REDUCTION OF HEMOGLOBIN AND METHEMOGLOBIN : IV. THE
      INHIBITION OF "SPONTANEOUS" METHEMOGLOBIN FORMATION.
AB  - It is well known that methemoglobin is gradually formed in sterile blood or
      hemoglobin solutions which are stored under the usual conditions. If the
      hemoglobin is reduced by biological agents and stored in the absence of air, the
      formation of methemoglobin is inhibited, or wholly prevented. The reasons for
      this are discussed.

PMID- 19869010
TI  - BIOLOGY OF BACTERIUM LEPISEPTICUM : I. EFFECTS OF OXYGEN TENSION AND THE PRESENCE
      OF RABBIT BLOOD ON GROWTH, DISSOCIATION, AND VIRULENCE.
AB  - 1. Bacterium lepisepticum, Type D, inoculated in small amounts into meat extract
      broth, pH 7.4, under aerobic conditions failed to grow. Larger inoculations
      underwent a period of lag before the logarithmic growth phase began. 2. In this
      medium, dissociation of Microbe D to the variant G occurred readily. 3. A lowered
      oxygen tension in this broth resulted in growth of small numbers of Type D with
      no lag and great inhibition of the type dissociation process. 4. Similar optimum
      growth conditions were obtained by adding to extract broth, under aerobic
      conditions, autoclaved or unautoclaved rabbit blood in very small amounts, 0.0003
      per cent, just sufficient to give a positive benzidine test.

PMID- 19869011
TI  - VARIATIONS IN SPECIFICITY AND VIRULENCE OF PNEUMOCOCCI DURING GROWTH IN VITRO.
AB  - When pneumococci are grown repeatedly in broth containing immune serum or bile,
      they become less virulent and less type-specific. These changes are apparently
      due to the fact that under the conditions mentioned a number of organisms appear
      which have lost certain properties. These variant organisms form colonies
      differing in appearance from the colonies of the typical organisms, and cultures
      made from the atypical colonies are avirulent and are not type-specific, The
      degree of modification of the original culture is directly related to the
      relative number of organisms that have undergone variation. After prolonged
      growth in bile or homologous immune serum variation may have become manifest in
      all the bacteria of the cultures and the change is then irreversible. The
      significance of these findings as regards the epidemiology of pneumococcus
      infections is noted.

PMID- 19869012
TI  - JAUNDICE AS AN EXPRESSION OF THE PHYSIOLOGICAL WASTAGE OF CORPUSCLES.
AB  - The jaundice that develops after obstruction of the common duct in the absence of
      complications, expresses the physiological wastage of corpuscles occurring from
      day to day; and the intensity of the bilirubinemia varies as does the total of
      functioning hemoglobin-containing tissue from which this wastage takes place.
      There is to be observed a constantly readjusted direct relationship between
      hemoglobin percentage, bilirubinemia, and, by corollary, bilirubinuria. Induced
      losses of red cells find expression at once in a lessened accumulation and
      excretion of bile pigment; and as the regeneration of hemoglobin takes place the
      amount of bile pigment increases pari passu both in plasma and urine. The
      jaundice of bile retention is far less pronounced during secondary anemia than
      when the individual is full blooded, other things being equal. During
      uncomplicated obstructive jaundice the intercurrent changes in bilirubinemia
      correspond closely with those in circulating hemoglobin even when tissue icterus
      is of long standing. The fact indicates the presence of a barrier to the
      distribution of bile pigment from the blood, and such a barrier is to be found in
      the walls of the vessels. Its influence is at once evident on comparing lymph
      specimens and blood specimens from the long jaundiced animal. The amount of bile
      pigment in the lymph is then seen to be negligible, relatively speaking. Tissue
      icterus should be thought of as, ordinarily, the highly imperfect secondary
      expression of a condition which tends to be localized to the blood pool. On
      occasion more pigment than usual may escape from this pool, as for example into
      the wheats of the yellow urticaria described by clinicians.

PMID- 19869013
TI  - SUPPRESSION OF BILE AS A RESULT OF IMPAIRMENT OF LIVER FUNCTION.
AB  - Prolonged chloroform anesthesia causes an acute suppression of bile, as evidenced
      by the secretion of a thin "white bile" from which bilirubin, cholesterol, and
      bile salts are absent. The failure of the liver to secrete bilirubin under such
      circumstances is not due to failure of the pigment to be formed within the body.
      Indeed an unusual amount is elaborated after chloroform anesthesia because of a
      blood destruction. The evidence all goes to show that the bile suppression is
      consequent upon a functional disturbance of the liver, not upon obstruction to
      outflow. Even uncomplicated biliary obstruction, as when the common duct is tied
      in animals otherwise normal, results in a disturbance of the liver cells such
      that their secretory function is impaired, as shown by the inability to take up
      and secrete sodium indigotate. The various circumstances under which white bile
      may be formed are considered and the clinical implications of the phenomenon are
      discussed.

PMID- 19869014
TI  - EXPERIMENTAL PNEUMONIA IN MICE FOLLOWING THE INHALATION OF STREPTOCOCCUS
      HAEMOLYTICUS AND OF FRIEDLANDER'S BACILLUS.
AB  - The results of these experiments support the previous observations that mice
      react in different ways to the inhalation of different bacteria. If normal mice
      are sprayed with hemolytic streptococci or Friedlander's bacillus, these
      organisms may be recovered from the lungs and heart's blood for a number of days
      after exposure. A large number of mice so exposed die of a septicemia during the
      30 days following spraying. Consolidation of one or more lobes is not rare. If
      normal mice are exposed to an atmosphere of pneumococci, however, the organisms
      rapidly disappear from the lungs and only an occasional mouse succumbs to
      pneumococcus septicemia. In order to cause the pneumococcus to invade, the mice
      must first be alcoholized. If mice are first alcoholized and then exposed to a
      pneumococcus atmosphere, the pneumococci persist for a longer time in the lungs
      and a number will die of septicemia, a state of affairs which resembles that seen
      after the administration to normal mice of the other two organisms studied. In
      order to produce pneumococcus lobar consolidation, however, the mice must be
      first partially immunized and then allowed to inhale the organisms while under
      the influence of alcohol. A large percentage of both the normal and immune mice
      so alcoholized die within 5 days of exposure. There also appears to be a definite
      relation between the mortality and the length of time inspired bacteria persist
      in the lungs. Whether this lag in removal allows multiplication of the bacteria
      and massive infection to occur has not been determined. Following inhalation of
      pneumococcus, the organisms were either removed rapidly and without apparent
      detriment to the animal, or, as in the case of the alcoholized mice, invasion
      occurred, in which event the mouse usually succumbed rapidly, localization in the
      lung only occurring in partially immune animals. In the case of the hemolytic
      streptococci and Bacillus friedlaenderi, however, the whole process of removal
      and infection seems to be slower. Infection and pneumonia occurred more often.
      These organisms seem to possess much greater invasive power when inhaled than the
      pneumococcus, though on intraperitoneal or subcutaneous inoculation, pneumococcus
      is highly virulent for normal mice.

PMID- 19869015
TI  - PATHOLOGY OF THE EXPERIMENTAL PNEUMONIAS IN MICE FOLLOWING INHALATION OF
      STREPTOCOCCUS HAEMOLYTICUS, OF FRIEDLANDER'S BACILLUS, AND OF PNEUMOCOCCUS.
AB  - 1. Pulmonary consolidation may be produced in normal mice by the inhalation of
      Friedlander's bacillus or Streptococcus haemolylicus. 2. The initial lesion is in
      both instances interstitial in character and the spread is by way of the
      interstitial tissue, though the ultimate consolidation may come to resemble in
      the gross a lobar pneumonia. 3. The lesions grossly and microscopically may be
      distinguished from the lobar consolidation associated with pneumococcus infection
      of the lung. 4. Friedlander's bacillus and Streptococcus haemolyticus give rise
      to pneumonia in mice previously normal, whereas the pneumococcus produces
      pulmonary lesions only under special circumstances, as when the animals are
      alcoholized after partial immunization.

PMID- 19869016
TI  - PNEUMONIA ASSOCIATED WITH BACILLUS ABORTUS (BANG) IN FETUSES AND NEW-BORN CALVES.
AB  - A pneumonic condition in fetuses and new-born calves due to Bacillus abortus is
      pointed out for the first time, and its character, extent, and bearing on the
      epidemiology of pneumonia discussed.

PMID- 19869017
TI  - THE COMPOSITE NATURE OF A PURE CULTURE OF A VIRULENT PNEUMOCOCCUS.
AB  - The experiments reported in this paper indicate that a pure culture of a virulent
      Type I pneumococcus as transferred under ordinary conditions is made up of
      individuals which are not identical in virulence for animals,-in bile solubility,
      or in their power to multiply under unfavorable conditions. By mechanical
      analysis alone no avirulent strains were obtained from the virulent strain, but
      one, Strain C, was separated which proved to be much more virulent for rabbits
      than its fellows. The virulent, colony-pure, Type I pneumococcus was allowed to
      multiply for several transplants in a series of cultures in (a) pneumococcus
      antiserum broth, (b) bile broth, and (c) slightly acid broth. When cultures from
      each series were plated on blood agar there appeared amid the ordinary
      pneumococcus colonies some that were totally different therefrom. Cultures from
      these new colonies were macroscopically bile-soluble, fermented inulin, and
      produced methemoglobin. Their occurrence under these different sets of conditions
      as well as careful controls excluded the possibility of a derivation by
      contamination. The new strains were avirulent and did not become virulent on
      repeated passage through mice. Antisera procured by the injection of them into
      rabbits were found to contain agglutinins for Type I pneumococci, but no
      protective antibodies. The avirulent strains are evidently pneumococci. It is
      possible that they may have been present in the parent strain and the unfavorable
      conditions of growth (immune serum, bile, slight acidity) might have allowed them
      to multiply while repressing the virulent forms. The individuals composing the
      pneumococcus culture are not all equally bile-soluble. By means of differential
      bile solubility, the avirulent forms were obtained within 12 hours from the
      parent strain though only twice in six experiments. It is possible that the
      avirulent individuals might not have been present in the 26 hour stock culture
      which yielded one of the positive results and that the organisms surviving the
      lysis might have retained sufficient bile after washing with isotonic salt
      solution for this to be responsible for the development of the variant. The fact
      that the identical experiment with the virulent Derivative Strain C revealed no
      avirulent forms renders it likely that the majority of the avirulent forms
      originated from the virulent individuals under the unfavorable conditions. The
      correctness of this interpretation is proven by the finding of these avirulent
      forms in virulent single cell derivative strains grown under unfavorable
      conditions. By contrast, strains of these avirulent forms descended from single
      diplococci did not revert to virulence. Apparently there had occurred a genuine
      bacterial mutation. These results in general are in accord with those of
      Griffith(8) who has made a more careful study of the properties of variants of
      pneumococci. He has recorded the occasional reversion of a variant when the
      single colony culture has been made after one serum passage. There is no
      reference in his article to any experiments with strains derived by the isolation
      of single diplococci. Further evidence of the composite nature of the parent
      strain as ordinarily grown is presented by the difference in the effect of long
      continued growth in immune serum on the pure line strains and on the parent
      strain itself. The pure line strains, equally as virulent for mice as the parent,
      and one of them, Strain C, more virulent for rabbits, became less virulent than
      the parent strain after twelve transplants in immune serum. Growth in normal
      horse serum did not affect the virulence. The single cell derivative, moreover,
      was found to be the less resistant to bile when grown in increasing
      concentrations of this lytic substance. The virulent Derivative Strain C became
      avirulent in eleven transplants in acid broth pH 6.8 while the parent strain,
      though reduced in virulence, was still lethal in doses of 0.001 cc. after the
      same number of transplants in this medium.

PMID- 19869018
TI  - SURFACE TENSION OF SERUM : XII. A TECHNIQUE FOR THE ACCURATE STUDY OF THE DROP IN
      FUNCTION OF THE TIME.
AB  - A technique is described for the study of the adsorption in function of the time
      of molecules of colloidal substances in the surface layer of water. This
      technique eliminates previous causes of error, in particular the individual
      coefficient. The curves obtained by plotting the data for serum at various
      dilutions give a clear picture of the phenomenon, and show that the low values of
      the initial surface tension of pure serum and serum at low dilutions are due to
      the extreme rapidity of adsorption of the molecules in the surface layer, owing
      to their high concentration. Evidence is given that colloidal substances in
      solution substantially lower the surface tension of the solvent, even when they
      are in too small a number to form an homogeneous monolayer.

PMID- 19869019
TI  - DISTINCTIVE CHARACTERISTICS OF INFECTIONS PRODUCED BY TREPONEMA PERTENUE IN THE
      RABBIT.
AB  - From a study of rabbits inoculated intratesticularly with two strains of
      treponemata derived from patients suffering from clinical yaws, it was found that
      a characteristic feature of the reaction to the infection was a well marked
      periorchitis of a granular or finely nodular type with or without a diffuse
      involvement of the tunic. While lesions of the testicular parenchyma also
      occurred they were relatively inconspicuous and consisted either of a minor
      diffuse orchitis which was usually followed by atrophy and fibrosis of the organ,
      or of small nodules; or there might be a combination of diffuse and nodular
      lesions. The granular periorchitis could be recognized clinically almost as soon
      as any change could be detected in the testicle, that is, about 3 weeks after
      inoculation; in the following month the covering of the testicle became studded
      with numerous tiny indurated nodules. Subsequently regression and healing took
      place and in the majority of animals no lesions were found 3 months after
      inoculation. In some animals residual lesions persisted for as long as 6 months.
      The granular periorchitis was a practically constant feature of the infection and
      was unlike any lesion of the tunic observed in experimental syphilis of the
      rabbit. Treponemata were numerous in the lesions of the tunic and somewhat less
      so in the testicle itself. Dissemination of organisms to the uninoculated
      testicle and to the inguinal lymph nodes was demonstrated by animal inoculation
      although the clinical signs of a metastatic orchitis and periorchitis were slight
      and a lymph adenitis was an inconstant feature of the infection. Generalized
      lesions in remote parts of the body, similar to those occurring in experimental
      syphilis of the rabbit, were not observed.

PMID- 19869020
TI  - THE RELATIONSHIP BETWEEN THE GROWTH CAPACITY OF PRIMARY TUMORS AND THE
      DISTRIBUTION OF METASTASES OF A TRANSPLANTED TUMOR OF THE RABBIT.
AB  - As an adjunct to the study of a transplantable malignant tumor of the rabbit an
      index of malignancy has been developed which has proven useful in evaluating the
      severity of the disease for the purpose of statistical investigations. The index
      consists of two figures, one of which expresses the growth capacity of the
      primary lesion on a volume basis, and the other the extent of the metastatic
      lesions according to the distribution of peripheral tumors. In the present
      communication these two values for each animal are utilized for the study of the
      relationship existing between the size of the primary tumor and the distribution
      of metastases in this experimental tumor. The data from a group of 128 rabbits
      form the basis of the analysis. These animals represent three entire series that
      had been used for the purposes of other experiments at various times, all,
      however, conducted under carefully controlled uniform conditions. The indices of
      malignancy of these animals were analyzed by means of graphs, in which individual
      values are preserved while at the same time investigation of mass behavior is
      permitted. From this analysis it is concluded (1) that the severity of the
      disease as a whole is very irregular among individuals of a series and from
      series to series, and (2) that the relationship between the extent of the primary
      lesions and that of the secondary lesions is inconstant among individuals but
      assumes definite proportions when the data are viewed in the mass. For the mass
      proportion between the two phases of the disease is predominatingly a direct one,
      but in certain small groups of seriously affected rabbits the proportion shows a
      tendency to reversal, while, in addition, there occurs a reduction in the rate of
      growth of the primary tumor, which reduction, together with the reversal in
      relationship, appears to be more pronounced from series to series as malignancy
      increases. An attempt has been made to account for these results in the light of
      what has been ascertained of the modes of defense of the rabbit host against the
      inroads of the cells of this transplanted tumor.

PMID- 19869021
TI  - EXPERIMENTAL OBSTRUCTION OF THE JEJUNUM : EFFECT OF SODIUM CHLORIDE INTRODUCED
      DIRECTLY INTO THE LUMEN OF THE INTESTINE BELOW THE POINT OF OBSTRUCTION.
AB  - Chemical changes are reported occurring in the blood of animals with obstruction
      of the jejunum, in which distilled water or sodium chloride solutions were
      introduced directly into the lumen of the intestine below the point of
      obstruction. Distilled water given daily from the beginning of the obstruction,
      had no influence on the development or course of the toxemia. 1 and 2 per cent
      salt solutions prevented a toxemia in uncomplicated cases. One animal so treated
      lived 30 days. Distilled water, given after the onset of toxemia, did not alter
      the progress or outcome of the toxemia. 10 per cent sodium chloride solution,
      administered after the onset of toxemia, controlled it in most cases for a long
      period. Hydrochloric acid had no effect on the course of the toxemia.

PMID- 19869022
TI  - STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY : III. ABSORPTION OF PIGMENTS OF
      BILIARY DERIVATION FROM THE INTESTINE.
AB  - Direct proof of the absorption of bile pigments from the intestinal tract is
      presented. Feedings of pure bilirubin by mouth to dogs, like those of whole bile,
      increase greatly the amount of this pigment in the hepatic bile. Control feedings
      of bile salts, while greatly increasing the bile quantity, cause no change in the
      pigment output. Instillations of pure bilirubin directly into the duodenum of
      dogs, appropriately intubated, are followed by pronounced increases in the
      bilirubin output in the bile. Feedings of pure urobilin to dogs, yielding
      urobilin-free bile, as result of diversion of the secretion from the intestine,
      are followed by the appearance of this pigment in the bile.

PMID- 19869023
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : IV. INDICATED DIFFERENCES
      IN THE REACTION OF THE ORGANS ON VITAL STAINING WITH PHTHALEINS.
AB  - In continuation of the observations on vital staining by means of phthalein
      indicators, reported in a previous paper, some members of the group with acid
      ranges have been employed. The results accord closely with those already
      obtained, in pointing to the existence of characteristic differences in the
      reaction within the organs. Roughly speaking, these latter fall into two groups.
      Within the members of the one a noteworthy acidity would appear to prevail,
      whereas in those of the other acidity seems slight at most, and in a few
      instances signs of a faint alkalinity are to be met. In general the "acid" organs
      are such as have a great metabolic activity whereas the "neutral" group manifest
      but an inconsiderable one. All of the tissues examined seem to be relatively acid
      compared with the blood plasma. The findings with the phthaleins as a group are
      discussed.

PMID- 19869024
TI  - SKIN REACTIONS TO SIMULTANEOUS TREATMENTS WITH RADIANT HEAT AND SOFT X-RAYS.
AB  - Guinea pigs have been exposed to suberythema doses of soft x-rays, to radiant
      heat of intensity about critical for producing slight burns, and to both
      radiations simultaneously. No erythema was produced in the skin of the animals
      exposed to x-rays alone and only slight burns resulted in 50 per cent of the
      animals exposed to heat radiation alone. The animals exposed to heat and x
      radiation simultaneously developed well marked burns which healed much more
      slowly than those produced by heat alone.

PMID- 19869025
TI  - THE LIVER AS A SOURCE OF BACTERIAL AGGLUTININ.
AB  - Serum and tissues containing agglutinin for the hog cholera bacillus may be dried
      in vacuo over sulfuric acid without appreciably injuring the antibody. The
      desiccated material when extracted with appropriate amounts of distilled water
      offers a basis for accurate comparison of antibody content. The greatest
      concentration of agglutinin occurred in the liver, provided the animals injected
      with small amounts of antigen were killed within a short period. The serum of
      those more highly immunized contained the greatest concentration of antibody. A
      single injection of antigen into a radicle of the mesenteric vein resulted in a
      considerable concentration of agglutinin in the liver. Other experiments
      indicated that the liver does not act as a reservoir for the antibody. It has
      also been shown that this concentration of agglutinin cannot be ascribed to the
      blood left within the liver, since the blood serum was relatively poor in
      antibody. The experiments indicate that the agglutinin was produced within the
      liver.

PMID- 19869026
TI  - SURFACE TENSION OF SERUM : XIII. ON CERTAIN PHYSICOCHEMICAL CHANGES IN SERUM AS A
      RESULT OF IMMUNIZATION.
AB  - 1. The injection of antigen into an animal determines a gradual change in the
      blood fluid which finds expression in two physicochemical manifestations that can
      readily be followed, namely a decrease in the static value of the surface tension
      of serum solutions, and a special form of crystallization when serum diluted with
      isotonic sodium chloride solution is allowed to evaporate under certain
      conditions. 2. The change in the blood is at a maximum around the 13th day after
      the first antigen injection, and decreases progressively thereafter until it can
      no longer be observed, which is usually around the 30th day. 3. The change
      follows the same course, whether a single large injection of antigen is made, or
      many smaller ones. It begins at the same time in either case, it comes to a
      maximum after the same period, and in its subsequent course it is not affected by
      the reinjection of antigen. The manifestations of the change would appear to be
      independent of the presence of antigen in the circulation. 4. The mean length of
      the protein molecules of the immune serum obtained after the injection of the
      antigen dealt with is little if at all different from that of the protein
      molecules of normal serum. 5. It is possible that this reaction is independent of
      the antibody formation.

PMID- 19869027
TI  - THE OCCURRENCE OF STIGMATA OF CONGENITAL SYPHILIS IN RABBITS WITH ESPECIAL
      REFERENCE TO THE FACTOR OF INHERITANCE.
AB  - The report is concerned with the occurrence of stigmata of syphilis in the
      progeny of syphilitic rabbits and the probable cause for such conditions in cases
      where no infection can be demonstrated. The history of a group of animals
      presenting these conditions is given and possible causes are discussed in the
      light of evidence derived from a study of these animals. In this instance, it
      appeared that the lesions suggesting syphilis were of functional rather than of
      infectious origin and that heredity was an important factor in determining their
      occurrence.

PMID- 19869028
TI  - EXPERIMENTAL PRODUCTION AND TRANSMISSION OF TAR SARCOMAS IN CHICKENS.
AB  - Two spindle cell sarcomas have developed as the result, of injection of coal tar
      into induced embryomas in chickens. One of these, transplanted to other chickens
      for eleven generations, is highly invasive in character, and metastasizes freely.
      Attempts to transmit this neoplasm by a filtrate or desiccate of the tumor have
      failed of success.

PMID- 19869029
TI  - A GROUP OF MICROORGANISMS TRANSMITTED HEREDITARILY IN TICKS AND APPARENTLY
      UNASSOCIATED WITH DISEASE.
AB  - 1. Pleomorphic, bacterium-like, Gram-negative, intracellular microorganisms,
      which stained much less intensely with ordinary dyes than most bacteria were
      found in sixteen species of ticks comprising examples of the Argasidae and the
      Ixodidae. 2. In six of these species studied intensively slight differences in
      the microorganisms were detected, sufficient to permit identification of the
      vectors by microscopic examination of the microorganism alone. 3. No evidence was
      seen of injury to the tissues of the arachnid hosts of the microorganisms other
      than that incident to mechanical distention of the cells containing them. 4. The
      detection of the microorganisms in the eggs of ten species, in the unfed larvae
      of eight species, and at nearly related stages throughout the life cycle of three
      others leads to the conclusion that they are transmitted hereditarily.

PMID- 19869030
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : VII. THE EFFECT OF SELECTIVE BREEDING ON HOST RESISTANCE. FURTHER
      STUDIES.
AB  - 1. Survivors of an experimental mouse typhoid infection, selected and bred for a
      number of consecutive generations, give birth to offspring which are more
      resistant to the disease than a random group of the same inbred race. 2.
      Offspring of females most susceptible to this infection give birth to individuals
      which are more susceptible than a group of similar unselected mice.

PMID- 19869031
TI  - STUDIES IN EXPERIMENTAL SYPHILIS : III. FURTHER OBSERVATIONS ON THE POSSIBILITY
      OF CURE OF SYPHILIS IN THE RABBIT WITH ARSPHENAMINE.
AB  - Syphilitic rabbits can be treated with arsphenamine in such a manner as to render
      the lymph nodes incapable of transmitting the infection to normal rabbits. This
      can be accomplished if treatment is begun either early or comparatively late in
      the course of the disease. If treatment is begun early, the animals are almost
      uniformly susceptible to a second infection, whereas, if it is begun late, they
      are almost uniformly refractory to a second infection. It is suggested that this
      refractory state in rabbits may be explained by the existence of an acquired
      immunity which persists after the abolition of the disease, rather than to the
      persistence of the first infection. It would appear that it is possible under
      certain conditions to reinoculate rabbits and produce generalized infection
      without producing any lesion at the portal of entry.

PMID- 19869032
TI  - STUDIES IN EXPERIMENTAL SYPHILIS : IV. THE SURVIVAL OF TREPONEMA PALLIDUM IN THE
      INTERNAL ORGANS OF TREATED AND UNTREATED RABBITS.
AB  - Simultaneous transfers to the testes of normal rabbits of circulating blood,
      heart muscle, liver, brain, spleen and bone marrow (mixed), inoculated testicle,
      and popliteal lymph nodes from a series of untreated syphilitic rabbits,
      demonstrated the persistence of the original infection unifomnly in the lymph
      nodes and less regularly in the liver, mixed spleen and bone marrow, and testis
      originally inoculated. In one instance the circulating blood was found to be
      infectious. Transfer of similar tissues from syphilitic rabbits treated with
      arsphenamine late in the course of the disease failed to disclose syphilitic
      infection of any of these tissues. In one animal, in which keratitis developed
      both before and after treatment, the blood, internal organs, and lymph nodes were
      found to be non-infectious in spite of the fact that the cornea was shown to be
      the site of a syphilitic inflammation. Transfer of lymph nodes or internal organs
      of treated syphilitic rabbits is probably the best method of evaluating an
      antisyphilitic agent, but it must be supplemented by careful observation of
      treated animals over an appreciable interval of time following treatment. The
      results of this study support the idea that failure to reinoculate a treated
      syphilitic animal does not necessarily mean the existence of the first infection
      but might beinterpreted as indicating the presence of an acquired resistance
      which persists in rabbits in which no trace of the first infection can be
      demonstrated.

PMID- 19869033
TI  - BLOOD SUGAR STUDIES : I. RAPID ALTERATIONS IN THE BLOOD SUGAR LEVEL OF RABBITS AS
      RESULT OF INTRAVENOUS INJECTIONS OF KILLED BACTERIA OF VARIOUS TYPES.
AB  - A rapid rise in the blood sugar level of rabbits was produced by intravenous
      injections of killed Bacillus proteus, Bacillus coli, and Bacillus paratyphosus
      B, which returned to nearly the previous level in a few hours time. A less
      pronounced rise in blood sugar was produced by killed Bacillus paratyphosus A and
      Bacillus enteritidis.

PMID- 19869034
TI  - BLOOD SUGAR STUDIES : II. BLOOD SUGAR CHANGES IN FATAL BACTERIAL ANAPHYLAXIS IN
      THE RABBIT.
AB  - 1. During bacterial anaphylaxis there is a gradual rise in the blood sugar level,
      which attains an extremely high value at the time of death. 2. The curve of blood
      sugar is quite similar whether anaphylaxis is induced by organisms which affect
      the blood sugar in the unsensitized animal or by organisms which have no such
      effect. 3. No instances occurred in which there was not a marked hyperglycemia in
      anaphylaxis.

PMID- 19869035
TI  - ORGAN WEIGHTS OF NORMAL RABBITS.
AB  - In November, 1921, a systematic study of normal rabbits was undertaken as a part
      of a more general investigation dealing with the subject of the animal organism
      in relation to disease. The present paper on organ weights is based on results
      obtained from a study of 350 male rabbits killed and examined between January 1,
      1922, and July 1, 1924. Methods of conducting the experiments are described and
      the results are summarized in the form of a table and a series of text-figures.
      The organs studied were the heart, liver, kidneys, spleen, thymus, testicles,
      brain, thyroid, parathyroids, suprarenals, hypophysis, pineal gland, and
      representative groups of lymph nodes. The results recorded include maximum,
      minimum, and average weights, the median, the mode, the standard deviation, the
      probable error, the coefficient of variation, and the percentage distribution of
      organs of different weights. No final conclusions are drawn but it is pointed out
      that the results obtained are comparable to those that have been reported from
      similar studies of organ weight in man. Attention is also directed to the
      tendency to the occurrence of wide variations in the weights of nearly all
      organs, and to an apparent difference in the degree of correlation that exists
      between organ weight and body weight in the case of certain organs. In this
      connection it is pointed out that within certain limits the weight of the brain,
      in particular, and of other organs to a lesser degree appears to be independent
      of body weight. The results recorded in this paper are regarded as representing
      approximate values which are affected by numerous conditions for which correction
      should be made. These conditions will be considered in subsequent papers.

PMID- 19869036
TI  - DRAINAGE OF THE THORACIC DUCT IN EXPERIMENTAL PERITONITIS.
AB  - 1. When care is taken to produce a peritonitis, which in itself is almost
      uniformly fatal, drainage of the thoracic duct in dogs has no favorable influence
      upon the course or result of the peritonitis. 2. Under the conditions of my
      experiments the thoracic duct did not serve in any important way as a drainage
      tract for bacterial contamination of the peritoneal cavity.

PMID- 19869037
TI  - THE RELATION OF HYPERGLYCEMIA TO THE RELATIVE BLOOD VOLUME, CHLORINE
      CONCENTRATION, AND CHLORINE DISTRIBUTION IN THE BLOOD OF DOGS.
AB  - 1. In normal dogs experimental hyperglycemia causes a prompt dilution of the
      circulating blood. This is evidenced by the increase in the relative volume of
      serum and the reduction of the erythrocyte counts. If the hyperglycemia is large,
      the viscosity of the blood is visibly diminished. 2. As the hyperglycemia
      increases there occurs a reduction of the serum chlorine concentration and an
      increase in the concentration of corpuscular chlorine. 3. Reduction of an
      artificial hyperglycemia restores the relative blood volumes to their normal
      status. The erythrocyte count rises to the normal and the corpuscular chlorine
      concentration is diminished. If the reduction is a large one, the viscosity of
      the blood is visibly increased. 4. The same types of conductivity-chloride
      discrepancy that occur in human blood are found in the blood of dogs. In
      addition, a third type is described. 5. Hyperglycemia does not cause the same
      changes in the volume of the average erythrocyte of the dog as it does in the
      case of human erythrocytes.

PMID- 19869038
TI  - SURFACE TENSION OF SERUM : XIV. CONCERNING THE CHANGE IN SURFACE TENSION
      OCCURRING AS A RESULT OF IMMUNIZATION.
AB  - The nature of the relation between the time-drop and antibody formation cannot be
      stated as yet. It is certain that the physicochemical change in the serum,
      detected by means of surface tension measurements, is not due directly to the
      antibody itself. Neither is it due to the direct action of the antigen on the
      serum, or to a change in the albumin-globulin ratio in this latter. Rather does
      it appear like antibody formation itself to be due to a tissue activity. Further
      experiments are being carried out on this subject.

PMID- 19869039
TI  - STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY : IV. UROBILIN AND THE DAMAGED
      LIVER.
AB  - A variety of evidence is presented, all of which supports the view that in the
      uninfected animal the intestinal tract is the only place of origin of urobilin,
      not merely under normal circumstances, but when there is biliary obstruction.
      Animals rendered urobilin-free by collection of all of the bile from the
      intubated common duct remain urobilin-free even after severe hepatic injury. In
      our experiments urobilinuria was never found after liver damage except when bile
      pigment was present in the intestine. Thus, for example, it appeared during the
      first days after Ugation of the common duct, but disappeared as the stools became
      acholic. When this had happened a small amount of urobilin-free bile, given by
      mouth, precipitated a prompt urobilinuria. After obstruction of the duct from one
      third of the liver, mild urobilinuria was found, but no bilirubinuria. In animals
      intubated for the collection of a part of the bile only, while the rest flowed to
      the duodenum through the ordinary channels, liver injury caused urobilinuria,
      unless indeed it was so severe as to lead to bile suppression, when almost at
      once the urobilinuria ceased, though the organism became jaundiced. The evidence
      here presented, when taken with that of our previous papers, clearly proves that
      urobilinuria is an expression of the inability of the liver cells to remove from
      circulation the urobilin brought by the portal stream, with result that the
      pigment passes on to kidney and urine. Urobilinuria occurs with a far less degree
      of liver injury than does bilirubinuria. Our work has, for the most part, been
      carried out with animals having uninfected livers and bile passages. But the
      influence of cholangitis with infection has been briefly discussed in the light
      of some preliminary observations. The influence of infection on the place of
      formation of urobilin and on the occurrence of urobilinuria will form the subject
      of another communication.

PMID- 19869040
TI  - ON THE ANTIGENS OF RED BLOOD CORPUSCLES : II. FLOCCULATION REACTIONS WITH
      ALCOHOLIC EXTRACTS OF ERYTHROCYTES.
AB  - 1. Flocculation reactions of anti-erythrocyte sera on emulsions of alcoholic
      extract of blood are described. 2. The reactions are markedly species-specific.
      3. Besides the homologous reactions certain others-"heterogenetic"" ones-have
      been observed, and in this way the existence of new examples of heterogenetic
      antibodies has been demonstrated. 4. Group-specific substances can be extracted
      from human erythrocytes with alcohol and demonstrated by flocculation with group
      specific immune sera. 5. A conception of the structure of cellular antigens based
      upon the known facts, is presented.

PMID- 19869041
TI  - LIPOIDS AS THE GROWTH-INHIBITING FACTOR IN SERUM.
AB  - The growth-inhibiting action of serum has been shown to be due largely to the
      lipoids. Serum from which the lipoids have been removed is much less inhibiting
      to the growth of fibroblasts in vitro than is the original serum, and only
      slightly more inhibiting than Tyrode solution. The lipoids extracted from the
      serum are toxic and more inhibiting to the growth of fibroblasts than the
      original serum. Lipoids extracted from chicken brain, chicken liver, egg, and
      embryonic tissue have likewise an inhibiting action.

PMID- 19869042
TI  - EFFECT OF PREPUBERTY CASTRATION ON SUBSEQUENT CANCER IMPLANTATION.
AB  - Male and female mice castrated during the first 7 weeks of life and implanted
      with cancer at later periods show a resistance definitely higher than do intact
      animals of the same age. This increased refractiveness is evident at 3 months
      after the operation but is more pronounced at 8 months to a year. Even castration
      in early adult life seems to increase the refractory state to later cancer
      inoculation. On the other hand, adult mice inoculated within a week after
      castration show slight if any evidence of increased resistance.

PMID- 19869043
TI  - EFFECTS OF OBSCURE LESIONS ON ORGAN WEIGHTS OF APPARENTLY NORMAL RABBITS.
AB  - A group of 350 normal rabbits was studied with reference to the occurrence of
      obscure lesions of various kinds and the probable or possible effect of such
      lesions or disease processes on organ weights. The results of the investigation
      are presented in the form of comparative tabulations. It was found that so long
      as the animals remained in apparently good health the values obtained for organ
      weights of animals with lesions did not differ materially from those for animals
      that were entirely free from lesions. There were, however, slight deviations from
      the normal which appeared to be significant in that they suggested a functional
      response similar in character to the more marked changes in mass and mass
      relationships that occur in rabbits presenting clinical symptoms of disease due
      to the same causes.

PMID- 19869044
TI  - THE INFLUENCE OF THE AUTONOMIC NERVOUS SYSTEM ON THE FUNCTION OF THE THYROID
      GLAND.
AB  - 1. There is a marked individual variation in the histological structure of the
      thyroid gland of rabbits examined at the same season under standard conditions.
      Although the microscopic appearance varies in different rabbits, the structure of
      the two lobes in the same animal does not differ. The variations are seen
      principally in the size and shape of the vesicles and in the quantity and
      character of the colloid. 2. With one lobe as a control no histological changes
      in the other lobe have been observed following section or stimulation of either
      the cervical sympathetic or the vagus and its branches.

PMID- 19869045
TI  - THE HISTOLOGICAL CHANGES IN THE THYROID GLAND OF THE RABBIT FOLLOWING LOBECTOMY.
AB  - 1. In a series of rabbits the changes which took place in the histology of the
      left lobe of the thyroid gland after excision of the right lobe have been studied
      at varied intervals of time. 2 days after the removal of one lobe the other lobe
      showed a slightly increased colloid content, an increased vacuolation of the
      colloid, and a slight increase in the size of the epithelial cells. At the end of
      a week the vesicles were greatly increased in size, distended with colloid, and
      the epithelial cells were flattened, while after 3 to 4 months signs of
      compensatory hypertrophy were present. 2. The changes observed were uninfluenced
      by division of the vagus or cervical sympathetic.

PMID- 19869046
TI  - THE FUNCTION OF MACROPHAGES IN LOCAL RESISTANCE TO BACTERIAL INFECTIONS.
AB  - Coincident with the marked macrophage reaction induced in the peritoneal cavity
      by oil injection, there is an increased resistance of this location to bacterial
      infections. Animals so prepared dispose of Bacillus coli in a much shorter time
      than normal animals, and survive multiples of the fatal doses of staphylococci
      and pneumococi. The amount of oil injected is in itself incapable of inhibiting
      bacterial growth, nor is cell-free exudate from an oil-injected animal potent in
      this regard. The macrophages in the exudate, on the other hand, actively
      phagocytize bacteria. These facts lead to the conclusion that the increased
      resistance is due primarily to the action of macrophages.

PMID- 19869047
TI  - AN EXPERIMENTAL STUDY OF THE RELATION OF THE OVARY TO FAT METABOLISM.
AB  - From these observations there seemed to be little doubt that the follicular fluid
      of the ovary contains an active growth-stimulating substance and one capable of
      initiating an active digestion of a foreign fat, which might otherwise remain
      unabsorbed for an indefinite time in the tissues of these animals (2). We have
      not attempted to ascertain whether this substance exciting growth and a digestion
      of the oil is the same or in any way related to the substance exciting estrus in
      these animals. That it may be a different substance from the estrus-exciting
      substance is suggested, however, by the fact that a similar excitant of growth
      and fat digestion has recently been extracted by the same method from the corpus
      luteum of pigs. These extracts of corpora lutea have not excited estrus in spayed
      rats. In the one rat in which the pure oil was absorbed, the cells did not invade
      the oil, but the capsule remained cellular and the oil gradually disappeared from
      the space. In these experiments in which the active substance was added to the
      oil the cells have always invaded the oil.

PMID- 19869048
TI  - THE RELATION OF THE VITAMINS TO THE REACTION INDUCED BY COAL TAR IN THE TISSUES
      OF ANIMALS.
AB  - Drops of coal tar introduced into the subcutaneous tissue attract the
      fibroblasts, endothelial and other cells to them. These cells suffer degenerative
      changes through this action of the tar and the animal suffers cachectic-like
      changes and death from large doses of it introduced into the subcutaneous tissue.
      This action of the coal tar is limited to a short period of time, after which it
      becomes inert. The cells which have been drawn to it and which have not
      completely degenerated then slowly recover. Where large numbers of these cells
      are drawn to the tar they grow and divide after recovering from the initial
      effects of the tar. Cancer may develop. Where only a few cells are drawn to the
      tar they lay down intercellular fibrils and a scar eventually develops. Vitamin A
      fed in more than ample quantities to these animals protects the animals and the
      cells against the toxic action of the tar and stimulates and prolongs their
      secondary growth. Vitamin B stimulates the secondary growth of these cells. This
      action is limited in extent and time. It is followed by an early degeneration and
      hyalinization of the tissue.

PMID- 19869049
TI  - STUDIES ON THE ETIOLOGY OF HEARTWATER : I. OBSERVATION OF A RICKETTSIA,
      RICKETTSIA RUMINANTIUM (N. SP.), IN THE TISSUES OF INFECTED ANIMALS.
AB  - A Gram-negative, intracellular, coccus-like microorganism was found in cases of
      heartwater in the three species which are susceptible to the disease; namely,
      goats, sheep, and cattle. It was absent in the case of control animals, both
      normal ones and those dying of some. other diseases. The presence of this
      microorganism was definitely related to the febrile reaction. It was most easily
      detected in the renal glomeruli and in the small capillaries of the cerebral
      cortex but probably occurred throughout the body. The microorganism was a typical
      endothelial parasite, being restricted in distribution to the endothelial cells
      of the smaller blood vessels and to portions of such elements which had broken
      off into the blood stream. It was never observed to cause injury to the cells
      other than those incident to mechanical distention through accumulation within
      them of many individuals in large densely packed masses which were
      characteristically spherical. A typical attribute was the presence of several of
      these masses within the cytoplasm of a single endothelial cell. In view of the
      association of this microorganism with heartwater, a disease of ruminants, and
      thus far the only one in which microorganisms resembling Rickettsioe have been
      reported, the designation Rickettsia ruminantium is proposed.

PMID- 19869050
TI  - STUDIES ON THE ETIOLOGY OF HEARTWATER : II. RICKETTSIA RUMINANTIUM (N. SP.) IN
      THE TISSUES OF TICKS TRANSMITTING THE DISEASE.
AB  - The evidence offered in the first of these studies indicative of a causative
      relationship between Rickettsia ruminantium and heartwater is supplemented by the
      following observations concerning the ticks which carry the disease. When larvae,
      which had taken no food since hatching, were allowed to feed upon cases of
      heartwater, they acquired Rickettsioe which appeared to be identical with those
      in the tissues of animals suffering from heartwater, whereas control larvae
      hatched from eggs deposited by the same female and fed on normal animals remained
      free of Rickettsioe. After larvae presumably infective had moulted, the resultant
      nymphae containing Rickettsioe in their alimentary tracts, when fed upon
      susceptible animals produced in them typical attacks of heartwater, which the
      control nymphae, devoid of Rickettsioe, failed to do. The tissues of animals thus
      infected were found upon histological examination to contain typical
      Rickettsioelig;.

PMID- 19869051
TI  - PHYSIOLOGICAL ONTOGENY : A. CHICKEN EMBRYOS. IV. THE NEGATIVE ACCELERATION OF
      GROWTH WITH AGE AS DEMONSTRATED BY TISSUE CULTURES.
AB  - 1. Observations on tissue cultures of heart muscle from chicken embryos indicate
      that in general the growth rate of the individual cells decreases with age. The
      negative acceleration of growth is greatest at the beginning of life as in the
      intact embryo. 2. The latent period before growth commences increases with the
      age of the implanted tissue, but in a different fashion. The acceleration of the
      latent period is greatest near the end of the incubation period, thus
      demonstrating that the factors determining the initiation of growth and those
      determining the extent of growth are not similar.

PMID- 19869052
TI  - PHYSIOLOGICAL ONTOGENY : A. CHICKEN EMBRYOS. V. ON THE RATE OF THE HEART BEAT
      DURING THE DEVELOPMENT OF CHICKEN EMBRYOS.
AB  - These experiments show, then, that there are changes in rate which take place
      during the incubation period and that the direction of the curve expressing them
      changes in an orderly fashion. No attempt has yet been made to ascertain the
      influences operative in bringing about these alterations. It is our intention,
      however, to attempt to correlate them with such processes as changes in the rate
      of the general metabolism of the body, changes in structure of the heart muscle,
      and if possible with changes in the inherent dynamics of the muscle. It will be
      seen that the number of experiments at a given age is relatively speaking small.
      The temperature in spite of the precaution mentioned has likewise not been
      uniform, the range in the greatest number (38) of experiments having been 38
      degrees C. +/- 1 degrees . A few (four) counts have been made when the
      temperature was as low as 33.6 degrees C. and a few (two) also at a temperature
      as high as 40 degrees C. Although a curve as smooth as the one which has been
      drawn in all probability represents the general course of heart rate change, an
      explanation of the deviations which have been found is desirable. At least two
      influences which may be operative suggest themselves. First may be considered the
      effect of the unavoidable injury incident to cutting a window in the shell and
      removing so much of the shell membrane as to make the object visible. It has been
      a uniform practise to discard those eggs in which hemorrhage took place, so that
      if opening the egg has a share in the difficulty, this operation may be thought
      of as exerting a mechanical stimulus on a nervous or other controlling mechanism.
      But whether, especially at the early ages, a mechanism of such a nature exists
      within the embryo, we do not know. The search for one lies for the present beyond
      the range of our interest. A second influence responsible for the relatively
      large deviation in rate from the average may be that of fluctuations in
      temperature. The air of the room in which the observations were made was, in a
      given situation, fairly uniform at 38 degrees C. +/- 1.0 degrees . as the
      temperature records show. In the earlier experiments the temperature was read at
      a distance about 1 foot away from the egg. Between this point and the egg a
      difference unknown to us may well have existed. It is improbable, however, that
      it can have been more than 2 degrees C., that is to say, 38 degrees +/- 2 degrees
      . Roughly if the change in rate is approximately 15 beats per degree a maximum
      deviation of 30 beats may be expected. In point of fact a deviation as great as
      this did not take place. In later experiments the temperature was read in the
      immediate vicinity of the eggs, so that a correction can be made more accurately.
      There is in all probability a high degree of uniformity in the rate of the heart
      of the chicken embryo at each stage of development, although variation is also
      found. What the extent of the deviation is that may properly be encountered we do
      not yet know. It is desirable to pursue this subject further. Observations will
      accordingly be made and will be reported later.

PMID- 19869053
TI  - PHYSIOLOGICAL ONTOGENY : A. CHICKEN EMBRYOS. VI. DIFFERENTIATION IN THE CHICKEN
      EMBRYO HEART FROM THE POINT OF VIEW OF STIMULUS PRODUCTION.
AB  - In these experiments we have shown that, with the technique adopted, differences
      in behavior are exhibited by fragments of the heart taken from different
      localities. The different localities behave in a more or less uniform manner. The
      pace-making function, for instance, is found at first throughout the cardiac tube
      but later it is restricted and comes to reside in a special small area at the
      back of the right auricle near the center. The pace-making system is able to
      develop a rate comparable to that shown by the whole intact heart, irrespective
      of the size of the fragment in which it is contained. Later, under the
      circumstances of the study, the ventricular structures lose the power of
      spontaneous contraction, and later still, the auricular ones also. It need
      scarcely be pointed out, however, that this loss refers only to the function of
      pace making. In its place, the various localities of the heart undoubtedly take
      on other capabilities. This is what is meant after all by differentiation. The
      question whether the pace-making and conduction systems reside in the remains of
      primitive portions of the cardiac tube in an undifferentiated form, or whether on
      the other hand these primitive portions develop into differentiated structures
      which preside over these functions may be reviewed afresh. Obviously the tube in
      its early state possesses these functions; obviously also the major part of the
      heart loses them during the course of development. A knowledge of the changes in
      form paralleling changes in function would have great interest. On this phase of
      the problem we hope to report later. On the basis of these observations,
      differentiation from the point of view of stimulus production may be viewed
      perhaps in this manner. Pace making, the conduction of impulses, and contraction
      are the primitive functions of the tube. As the tube develops into the adult
      structure, pace making and conduction are supposedly served by tissues resembling
      in structure the original ones. Whether as a matter of fact a structural change
      takes place is an interesting and important problem. Those portions of the heart
      which require to develop greater degrees of energy lose the primitive functions
      of pace making and conduction, and, in the transformation, take on a
      differentiated structure. It is, then, not the structures in which the primitive
      functions of pace making and conduction reside which are differentiated, but the
      greater mass of ventricular muscle. These reflections have their origin not only
      from our own work but they grow out of observations to be found in the writings
      of those (A. Keith and I. Mc-Kenzie) who call the nodal and conduction tissues in
      the heart, embryonic. But whether from the point of view developed here the use
      of this term is completely descriptive remains an interesting problem.

PMID- 19869054
TI  - STUDIES ON THE ANTIGENIC SUBSTANCE OF THE BACTERIAL CELL.
AB  - Putting together the results of such experiments as those outlined above, we can
      set down the following definite facts. 1. The substance of the bacterial cell can
      be roughly divided into two antigenic entities. One of these is the so called
      "nucleoprotein" substance, the other the residue substance or soluble material of
      Dochez and Avery and Avery and Heidelberger, both of which have been repeatedly
      characterized in preceding papers. 2. Immunization with the nucleoprotein, if
      such nucleoprotein is rendered free of bacterial bodies or fragments of bacterial
      bodies by Berkefeld filtration, incites the production only of antinucleoprotein
      antibodies which, with slight group overlapping, are species-specific but, as
      determined by the previous studies of Avery and, subsequently, those of
      Lancefield, are not type-specific to the same degree as the residue antibodies.
      3. Immunization with dissolved residue alone leads to no antibody formation
      whatever. This residue, as indicated in several of our own previous studies,
      represents the haptophore group upon which specificity depends and which, in the
      simple process of solution, is disrupted from another substance together with
      which it represented a complete antigen in the antibody-forming sense. 4. The
      formation of specific antiresidue antibodies is apparently dependent upon the
      injection of morphologically formed elements, at least as far as experiment can
      determine at the present time; for, as in the pneumococcus experiments, the most
      available process of solution and the injection of all the materials so obtained
      from the whole bacteria fails to yield antiresidue antibodies, as though in the
      mere process of dissolving the residue haptophore group were dissociated from its
      association with the larger molecule to which, in the whole bacteria, it lends
      specificity. 5. While antiresidue antibodies are only formed when such
      undisrupted bacterial cell substances are present in the immunizing substance,
      immunization with whole bacteria, even when attempts are made to preserve them
      from solution by formalin, leads to the formation of both antiresidue and
      antinucleoprotein antibodies, probably because a certain amount of solution
      inevitably takes place after injection within the animal body.

PMID- 19869055
TI  - STUDIES ON THE ETIOLOGY OF JAGZIEKTE : I. THE PRIMARY LESIONS.
AB  - The lungs of South African sheep, in a district in which jagziekte is appearing
      sporadically, differ from those of normal American sheep. Their structure is in
      general variable. They are more subject to the action of bacteria, demonstrable
      histologically, and to the effect of inhaled foreign material. The most
      significant difference, however, centers in the interalveolar tissue, which, in
      about 33 per cent of the animals, is definitely thickened beyond the range of
      variation in this direction observed in American sheep. The thickenings occur in
      localized areas several millimeters in diameter. They begin with engorgement of
      the alveolar capillaries and accumulation of macrophages and of lymphocytes. Many
      of the macrophages pass into the alveolar lumina and assume the appearance of
      typical epithelioid cells. These infiltrative and exudative changes are primary
      to the epithelial proliferations which always arise in tissues modified in this
      way and which it is proposed to describe in a second paper.

PMID- 19869056
TI  - STUDIES ON THE ETIOLOGY OF JAGZIEKTE : II. ORIGIN OF THE EPITHELIAL
      PROLIFERATIONS, AND THE SUBSEQUENT CHANGES.
AB  - The epithelial proliferations, which are so typical of jagziekte, are chiefly of
      alveolar origin. They appear in areas of infiltration and exudation identical
      histologically with those occurring in sheep which are to all appearances normal
      but which are derived from flocks in which the disease is endemic. They become
      very extensive and quite atypical in structure, but they never give rise to
      metastases, even to the adjacent lymph glands. The primary infiltration of the
      interalveolar tissue continues and may lead to fibrosis and extensive
      consolidation, or leucocytes may accumulate in large numbers, penetrate into the
      alveoli, and form areas of acute pneumonia. In fairly advanced cases of jagziekte
      it is common to find many stages of the reaction in one and the same lung. While
      it is possible that the disease may be due to a single and specific virus, and
      the epithelial lesions are certainly of a very special character, the
      pathological complex as a whole is such as might be caused by a variety of
      predisposing and exciting factors operating over a considerable period of time.

PMID- 19869057
TI  - IMMUNOLOGICAL REACTIONS OF THE ISOLATED CARBOHYDRATE AND PROTEIN OF PNEUMOCOCCUS.
AB  - The data presented in this paper clearly indicate that the isolated carbohydrate
      and nucleoprotein constituents of Pneumococcus differ both serologically and
      antigenically one from the other. Moreover, each of these fractions of the cell
      separately exhibits immunological properties distinct from those manifested by
      the whole organism of which they form a part. The carbohydrate is a protein-free
      polysaccharide and as such is devoid of the property of stimulating antibodies.
      Although in the free state, dissociated from other cellular substances, it is non
      antigenic, in this form it still retains the property of reacting specifically in
      anti-pneumococcus serum of the homologous type. Further, this nonprotein
      constituent is not reactive with antiprotein serum. In other words, neither
      pneumococcus carbohydrate nor protein as separate antigen gives rise to
      antibodies with specific affinities for the carbohydrate or so called soluble
      specific substance of Pneumococcus. The nucleoprotein of Pneumococcus, on the
      other hand, is antigenic. Immunization with this cell constituent gives rise to
      immune serum which precipitates solutions of pneumococcus protein without regard
      to the type from which it is derived. The interrelations of the carbohydrate and
      protein of Pneumococcus as they exist in the intact cell to form the complete
      antigen, and the interpretation of the differences in the antigenic properties of
      the whole bacterium as contrasted with those of its component parts are reserved
      for discussion in a subsequent paper.

PMID- 19869058
TI  - THE ANTIGENIC PROPERTIES OF SOLUTIONS OF PNEUMOCOCCUS.
AB  - 1. Intact pneumococci, possessing specific antigenic powers unimpaired by
      cultural or other procedures, give rise to agglutinins for organisms of the
      homologous type and to precipitins for the type-specific carbohydrate derived
      from them. 2. Solutions of pneumococci free of all formed elements, but
      containing the carbohydrate and protein of the original cell, fail to stimulate
      the formation of type-specific antibodies. Sera prepared in this manner do not
      react with the carbohydrate constituent of the cell and do not agglutinate
      organisms of the homologous type. The loss of this antigenic function is related
      to changes incurred during dissolution of the bacterial cell. 3. Solutions of the
      cellular substances of Pneumococcus, although lacking the specific antigen of the
      whole cell, induce the formation of antibodies reactive with pneumococcus protein
      regardless of the type from which the latter is derived.

PMID- 19869059
TI  - IMMUNOLOGICAL RELATIONSHIPS OF CELL CONSTITUENTS OF PNEUMOCOCCUS : SECOND PAPER.
AB  - In this paper the general immunological significance of the intact pneumococcus
      cell and of its protein and carbohydrate components is discussed.

PMID- 19869060
TI  - THE IMMUNOLOGICAL RELATIONSHIPS OF STREPTOCOCCUS VIRIDANS AND CERTAIN OF ITS
      CHEMICAL FRACTIONS : I. SEROLOGICAL REACTIONS OBTAINED WITH ANTIBACTERIAL SERA.
AB  - 1. Agglutination and precipitation by the specific substance of Streptococcus
      viridans are parallel phenomena. Separate specific substances have been extracted
      from strains which are distinct by ordinary serological tests. Preliminary
      chemical examination indicates that the specific substances may be complex
      carbohydrates. 2. A close relationship between nucleoproteins from different
      strains of Streptococcus viridans is suggested by the existence of a certain
      amount of cross-precipitation and a larger degree of cross-complement fixation.
      But the occurrence of stronger reactions with homologous nucleoproteins than with
      heterologous indicates that there is some degree of individual difference in
      proteins from separate strains. 3. Two distinct antibodies are present in the
      sera antibacterial for Streptococcus viridans: one of high titer implicated in
      the parallel phenomena of agglutination and precipitation by the soluble specific
      substance, the other usually of low titer and involved in precipitation by
      nucleoproteins but probably little, if at all, in agglutination. The significance
      of these results obtained from the study of antibacterial sera will be considered
      in the general discussion of the antigenic components of Streptococcus viridans
      after the results from the study of antinucleoprotein sera have been presented in
      the succeeding paper.

PMID- 19869061
TI  - THE IMMUNOLOGICAL RELATIONSHIPS OF STREPTOCOCCUS VIRIDANS AND CERTAIN OF ITS
      CHEMICAL FRACTIONS : II. SEROLOGICAL REACTIONS OBTAINED WITH ANTINUCLEOPROTEIN
      SERA.
AB  - 1. The immunological behavior of two cell constituents of nonhemolytic
      streptococci has been studied, (a) One, the so called nucleoprotein, is
      relatively non-specific and gives rise to an antibody which shows group reactions
      with nucleoproteins of related species. (b) The other is non-protein by
      qualitative chemical tests. Preliminary chemical examination has indicated that
      it may be a carbohydrate. Although this substance is highly reactive with the
      specific antibodies produced by the intact bacterial cell, yet in its chemically
      purified condition it is probably non-antigenic. Specific serological reactions
      with this substance are dosely related to specific agglutination of the
      microorganism. 2. The study of sera prepared by immunization with the chemically
      extracted protein has shown the presence of antibodies for nudeoproteins alone.
      No antibodies against the specific soluble substance have been found in these
      sera. The protein antibodies are little, if at all, concerned in causing
      agglutination. Precipitin tests, complement fixation reactions, and absorption
      experiments have been used to analyze the group relationships with the
      nucleoproteins of other species. The proteins of each species of Gram-positive
      cocci studied were immunologically similar within the species and showed definite
      relationships to the proteins from related species. Proteins from bacteria of
      unrelated species did not react with antisera against streptococcus protein. 3.
      Two distinct antibodies have been demonstrated in antisera prepared against
      living bacteria. By prolonged immunization it was found possible to produce sera
      with a high content of protein as well as specific antibodies. With ordinary
      methods, however, the immune sera had a low content of relatively non-specific
      protein antibodies but a high titer for specific antibodies. The specific
      antibodies were not reactive with proteins but were active with high dilutions of
      the soluble specific substance and were responsible for the parallel specific
      agglutination. Absorption experiments showed that the two antibodies in
      antibacterial sera were immunologically distinct.

PMID- 19869062
TI  - COMPENSATORY HYPERTROPHY OF THE THYMUS GLAND IN THE RAT.
AB  - Previous experimental work concerning enlargement of the thymus has dealt mainly
      with the regeneration which follows partial or subtotal removal, or with the
      regeneration which follows transplantation. We planned our experiments to obtain
      evidence of uncomplicated hypertrophy by removing one lobe and studying the
      enlargement of the remaining lobe. Our results clearly indicate that such
      hypertrophy takes place in young animals. They emphasize the functional
      importance of this gland before puberty, since the compensatory enlargement does
      not take place after puberty. The results further indicate that with the onset of
      involution there is a marked or almost total decline in the function of the
      gland, in spite of the fact that anatomically the thymus may persist to old age.
      With the appearance of a stimulus for regeneration, as, for instance,
      suprarenalectomy, the involuted gland takes on functional activity.

PMID- 19869063
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : II. EFFECT OF ALCOHOL ON THE
      BACTERIOPHAGE OF D'HERELLE.
AB  - When bacteriophage is precipitated by alcohol at room temperature its activity
      rapidly and progressively decreases until it is totally destroyed, between 6 and
      24 hours after exposure. If the percipitation is carried out at 7 degrees C. the
      destruction of lytic activity is considerably slower; measurable traces may be
      detected even after 4 weeks exposure to alcohol. Although the major portion of
      the lytic activity is found in the precipitate, the supernatant alcohol carries a
      measurable amount of lytic principle which remains active for several days. In
      all cases the residual lytic activity was found to be transmissible in series. In
      no instance were we able to observe the non-transmissible action ascribed by
      d'sHerelle to the enzyme. The persistence of traces of active principle after
      many weeks of exposure to alcohol at low temperature is not found to be due to
      the existence in the original filtrate of a fraction relatively resistant to the
      effect of alcohol. The inactivation of bacteriophage by alcohol seems, therefore,
      analogous to the alcoholic inactivation of certain enzymes and toxins.

PMID- 19869064
TI  - THE EFFECT OF OPERATIVE INTERFERENCE WITH THE CERVICAL SYMPATHETIC NERVOUS SYSTEM
      UPON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE NEOPLASM OF THE RABBIT.
AB  - The effect of the removal of the complete cervical sympathetic nervous system, of
      both superior and of both inferior cervical ganglia, and of a small portion of
      the cervical sympathetic nerve in the rabbit was studied in relation to the
      character of a malignant disease induced by a transplantable neoplasm. It was
      found that the general character of the disease which developed in the operated
      groups of animals was more severe than that of a similar sized control group.
      Comparisons of the mortality rate in the several groups, of the animal inddence
      of metastases, the number of metastatic foci, and the distribution of these
      secondary growths all showed this to be the case. There appeared, furthermore, to
      be differences in malignancy among the operated groups themselves. The most
      severe disease occurred in the group in which a portion of the sympathetic nerve
      only was removed (sympathotomy); that in the complete sympathectomy and superior
      sympathectomy groups was slightly less malignant; and that in the inferior group
      was much less so. These results have been interpreted as due to a less effective
      animal resistance, the mechanism of which has been interfered with in some way by
      the interference with the sympathetic nerves. The reasons for the difference in
      malignancy exhibited by the several operated groups are undetermined. A tentative
      explanation is suggested upon the basis of coordinating, favorable or deleterious
      functions subserved by the cervical sympathetic nervous system.

PMID- 19869065
TI  - COMPARATIVE STUDIES OF THE ACTION ON THE PNEUMOCOCCUS OF BILE ACIDS AND
      UNSATURATED FATTY ACIDS, FOUND IN BILE IN THE FORM OF SOAPS.
AB  - Ox bile contains the soaps of unsaturated higher fatty acids not only with one,
      but also with two and more than two double bonds, in a dilution of about 1:600.
      These substances, when isolated from bile, exert an antiseptic action on the
      pneumococcus in a dilution of approximately 1:50,000 and kill the organism in a
      dilution of 1:5000 in approximately 1 hour. As their action is, then, about 100
      times stronger than that of the conjugated bile acids, their presence in bile
      should be considered, whereas hitherto it has been entirely overlooked not only
      by bacteriologists but by physiologists as well. Since the soaps of unsaturated
      fatty acids do dissolve the pneumococcus cell in broth culture, Neufeld's (12)
      conclusion, is no longer valid.

PMID- 19869066
TI  - LOCAL IMMUNIZATION OF RABBITS TO CUTANEOUS INFECTION WITH STAPHYLOCOCCUS AUREUS.
AB  - 1. Bacterial filtrates were prepared by the methods described by Besredka, but
      these never developed any specific growth-inhibiting factors. 2. Such filtrates
      produced a strictly local immunity of the areas of the skin infiltrated but such
      protection was never greater than that produced with the broth from which they
      were prepared. This immunity was manifest within 8 hours and persisted at least
      15 days. 3. Transcutaneous treatment by moist dressings soaked in either filtrate
      or broth were entirely ineffective. 4. Sites of healed cutaneous lesions show a
      strictly local and nonspecific immunity for a period of 5 to 6 weeks. 5. Repeated
      intracutaneous infection with virulent staphylococci failed to produce a general
      cutaneous immunity.

PMID- 19869067
TI  - BIOLOGY OF BACTERIUM LEPISEPTICUM : II. THE STRUCTURE OF SOME IRON COMPOUNDS
      WHICH INFLUENCE THE GROWTH OF CERTAIN BACTERIA OF THE HEMOPHILIC, ANAEROBIC, AND
      HEMORRHAGIC SEPTICEMIA GROUPS.
AB  - Inorganic iron substances of known chemical structure have been tested for their
      ability to function as the X factor in the growth of bacteria of the hemophilic,
      anaerobic) and hemorrhagic septicemia groups. Each iron compound possessing this
      biocatalytic activity showed oxygen-absorbing and peroxidase properties. The
      interrelation of these mechanisms is discussed.

PMID- 19869068
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : III. SOME OF THE FACTORS DETERMINING
      THE NUMBER AND SIZE OF PLAQUES OF BACTERIAL LYSIS ON AGAR.
AB  - The experiments reported above confirm the fact that lytic principle is
      distributed in active solution in a state of indivisible units. This permits its
      quantitative evaluation by serial dilution, as well as by plating on agar. The
      latter method, however, often gives readings considerably lower than those
      obtained by the broth dilution method of titration. By varying the concentration
      of agar it has been possible to show that the discrepancy is due to adsorption of
      the lytic agent on agar. When the concentration of the latter is increased from
      0.3 per cent to 2.5 per cent the number of plaques of lysis is reduced more than
      100 times. At the same time the average size of the plaques also decreases
      approximately to one-tenth of the original. The size, as well as the number of
      plaques, has been found to depend also on the condition of the culture employed
      in titration. Thus, when the culture exposed to the action of lytic agent is
      composed of young susceptible bacteria, the greater the concentration of
      bacteria, the smaller the plaques. When the culture is composed partly of young
      and partly of old susceptible bacteria, both the size and the number of the
      plaques are diminished with the increase in the relative concentration of old
      bacteria. On the other hand, presence in the culture of resistant bacteria does
      not affect either the size or the number of the plaques so long as the relative
      concentration of susceptible bacteria in the culture is sufficient to allow
      formation of them. The plaques appearing in the presence of a high concentration
      of resistant variants in the culture are relatively indistinct owing to
      overgrowth. Under carefully controlled conditions the size of plaques is found to
      be determined by the character of the lytic filtrate. Thus in the case of lytic
      agents which act upon more than one bacterial species the size of the plaques
      remains constant, irrespective of the bacterial substratum used for the
      production of the active filtrate.

PMID- 19869069
TI  - EXPERIMENTAL RICKETS IN RABBITS.
AB  - Rickets has been produced experimentally in rabbits by the administration of
      diets deficient in the antirachitic organic factor and phosphorus but with a high
      calcium content. Cod liver oil added to these rickets-producing diets prevented
      the development of rickets in rabbits.

PMID- 19869070
TI  - STUDIES ON REGENERATION OF BACTERIOPHAGE : I. THE INFLUENCE OF PARTIAL
      ANAEROBIOSIS UPON REGENERATION OF A HIGHLY DILUTED LYTIC PRINCIPLE.
AB  - The regeneration of an extreme dilution of bacteriophage in a large volume of
      broth, as described by Gratia and De Kruif, is due to the influence of partial
      anaerobiosis upon the regeneration of the principle. The influence of partial
      anaerobiosis upon regeneration of an extremely diluted bacteriophage was
      investigated in relation to different factors with the following results. 1. The
      See PDF for Equation. expresses the degree of anaerobiosis necessary for
      regeneration of an extreme dilution of the bacteriophage. An increase in this
      ratio interferes with regeneration. 2. The regeneration of the highly diluted
      bacteriophage under partial anaerobiosis begins definitely at the 3rd hour of
      bacterial growth and is completed after about the 6th hour. 3. To obtain the full
      regeneration of an extreme dilution of bacteriophage it is sufficient to restrict
      for one hour the supply of air to a culture containing it, providing that this
      restriction be produced within the first 3 hours of the bacterial growth.

PMID- 19869071
TI  - THE PRODUCTION OF PERSISTENT ALOPECIA IN RABBITS BY X-RAYS OF VARIOUS DEGREES OF
      HARDNESS.
AB  - 1. The minimum dose of x-ray, of each of three degrees of hardness, required to
      produce persistent alopecia of the abdominal skin of normal white rabbits has
      been studied. 40 kilovolt rays filtered by 0.5 mm., 50 kilovolt rays filtered by
      1 mm., and 70 kilovolt rays filtered by 1.5 mm. of aluminium were employed. The
      70 kilovolt work is unfinished. 2. Under constant conditions of treatment, the
      animals were found to react with a high degree of consistency. 3. The values of
      the critical minimum doses expressed in terms of air ionization (pair of ions per
      gm. of air divided by 10(15)), for rays produced at 30, 40, 50, and 70 kilovolt
      peak, are 2.04, 3.7, 4.5, and over 5.1 respectively. The 30 kilovolt value is
      taken from a previous paper. 4. It is shown that the alopecia reaction does not
      run parallel to the erythema and pigmentation reactions.

PMID- 19869072
TI  - GROWTH AND PERSISTENCE OF FILTERABLE VIRUSES IN A TRANSPLANTABLE RABBIT NEOPLASM.
AB  - Virus III and vaccine virus multiply in a transplantable rabbit tumor of
      epithelial origin; are carried along with the tumor through an indefinite number
      of transplants; and despite an immunity developed by the rabbit host survive
      longer in the tumor than when injected into the testicles of normal rabbits.

PMID- 19869073
TI  - EXPERIMENTAL STUDIES WITH A SPIRAL ORGANISM FOUND IN A WILD RAT AND IDENTICAL
      WITH THE ORGANISM CAUSING RAT-BITE FEVER : SECOND PAPER.
AB  - 1. The spiral organism isolated from a wild rat has proved identical with that
      from a human case of rat-bite fever in Mexico City. 2. Rabbits can easily be
      infected with these organisms. 3. The subcutaneous inoculation of them is
      followed after 3 to 5 days by a local edema, induration, and inflammation:
      primary lesion. 4. About 8 days after the appearance of the primary lesion,
      edematous swellings and inflammation appear on the head and genitals: secondary
      lesions. 5. The organism can be transmitted from rabbit to rabbit by coitus. 6.
      Protective antibodies are to be found in the blood of infected rabbits at a time
      when the local lesions are still active. The peculiar character of certain of the
      lesions is probably due to the escape of the antibodies from the blood stream. 7.
      The organism belongs to the genus Treponema.

PMID- 19869074
TI  - BACTERIOPHAGE TESTS ON THE MECONIUM OF ABORTED FETUSES.
AB  - The theory that tissue cells are the source of bacteriophage was objected to by
      d'Herelle on the grounds that bacteriophage in the intestinal contents could
      penetrate the intestinal mucosa and migrate throughout the body and that any
      demonstration of its presence within the body fluids was in accordance with this
      phenomenon. The present work sought to overcome this objection by using tissues
      which had been exposed to but a single organism,-Bacillus abortus. Filtrates of
      meconium from six aborted bovine fetuses were tested against several strains of
      Bacillus abortus, but no evidence of a lytic principle could be demonstrated.
      Neither could it be shown that they contained a substance which would initiate
      lysis when tested against numerous strains of bovine colon bacilli.

PMID- 19869075
TI  - STUDIES ON THE RELATIONSHIP OF THE CHEMICAL CONSTITUENTS OF BLOOD AND
      CEREBROSPINAL FLUID.
AB  - 1. If due allowance is made for the slow rate of elaboration of cerebrospinal
      fluid and for the time that it takes for newly formed fluid to emerge from a
      needle in the cistema, the amount of sugar, chloride, and non-protein nitrogen in
      the fluid seems to follow in a general way their concentrations in the blood
      stream. 2. It is equally evident, however, that for any substance other factors
      besides its concentration in the blood stream play a part in its distribution
      between blood and cerebrospinal fluid.

PMID- 19869076
TI  - SPECIFIC INFECTIOUS CYSTITIS AND PYELONEPHRITIS OF COWS.
AB  - A specific infection of the urinary tract associated with a diphtheroid has been
      encountered in cows from three dairy herds. The most characteristic symptom is
      the frequent passage of turbid or blood-stained urine. The bladder was always
      found to be involved. The bladder walls were thickened, the mucosa swollen and
      reddened. Patches of exudate adherent to the bladder mucosa were frequently
      observed. In certain instances one or both ureters were thickened. In other cases
      one or both kidneys were involved. The kidney process seemed to originate in the
      pelvis and extend toward the medulla and cortex. The characteristic bacilli were
      always found in large numbers in the urinary sediment and the pelves of involved
      kidneys.

PMID- 19869077
TI  - THE EFFECT OF ETHYL URETHANE ANESTHESIA ON THE ACID-BASE EQUILIBRIUM AND CELL
      CONTENTS OF THE BLOOD.
AB  - When anesthesia is produced in rabbits or rats by injections of ethyl urethane,
      the C0(2) content and pH of the whole blood of the animal are more or less
      rapidly increased to a point where there is a marked uncompensated alkalosis
      which reaches its maximum at 24 hours and persists for 48 hours. The increase in
      the C0(2) content and pH of the whole blood is accompanied by a decrease in the
      circulating lymphocytes and an increase in the polymorphonuclear leucocytes.

PMID- 19869078
TI  - UROBILIN PHYSIOLOGY AND PATHOLOGY : V. THE RELATION BETWEEN UROBILIN AND
      CONDITIONS INVOLVING INCREASED RED CELL DESTRUCTION.
AB  - Further evidence is presented, in addition to that of our previous papers, that
      the intestinal tract is, under ordinary circumstances, the sole place of origin
      of urobilin. So long as the biliary tract remains sterile the presence of the
      pigment in bile and urine is entirely dependent upon the passage of bile to the
      intestine. Animals rendered urobilin-free by the collection of all the bile from
      the intubated, uninfected common duct, remain urobilin-free during and after
      extensive blood destruction caused by intravenous injections of distilled water,
      as also after reinjections of the animal's own blood, hemolyzed in vitro. No
      urobilin appears in the bile, urine, or feces of animals so intubated when blood
      destruction has been caused by sodium oleate, or by an agent, toluylenediamine,
      which damages the liver as well as the blood. On the other hand, when bile flow
      into the intestine is uninterrupted, urobilinuria occurs during blood destruction
      caused in any of the ways mentioned and it parallels, both in severity and
      duration, the destructive process. Merely increasing the amount of bilirubin
      within the intestines of healthy dogs by feeding urobilin-free bile, will lead to
      marked urobilinuria. The extravasation of blood into the tissues, resulting from
      the trauma of an operation for intubation of a bile duct, does not lead to
      urobilinuria in animals losing all of the bile after this operation, but may do
      so when only a small fraction of the bile is drained, while the remainder reaches
      the intestine as usual. The production of artificial hematomas, without
      operation, is not followed by urobilinuria, under the circumstances last
      mentioned, but merely by an increase in the bilirubin of the bile. The effect on
      the liver of the anesthetic employed during the intubation may be responsible for
      the difference in the two cases. During the course of certain intercurrent
      infections affecting some of the intubated animals, notably distemper, there was
      a drop in the hemoglobin percentage of the circulating blood, accompanied by an
      increased output of bile pigment or further by urobilinuria, when the conditions
      were such that bile still reached the intestine. The findings pointed to
      increased blood destruction as a factor in the urobilinuria. The evidence
      presented, taken with that of our previous papers, suffices to demonstrate, that
      urobilinuria, occurring during blood destruction, is primarily the result of an
      increased excretion of bilirubin from which, in turn, an unusually large quantity
      of urobilin is formed within the intestine. The liver fails to remove from the
      portal blood all of the latter pigment which is resorbed and consequently some of
      it reaches the kidneys and urine. Our work has been carried out on animals with
      uninfected biliary tracts and livers, save for one case which has special
      mention. The influence of infection of the biliary tract on the place of
      formation of urobilin and the development of urobilinuria will be discussed in a
      succeeding communication.

PMID- 19869079
TI  - EXPERIMENTS ON THE GLOMERULAR DISTRIBUTION OF BLOOD IN THE MAMMALIAN KIDNEY.
AB  - The results of thirteen control experiments, designed to show the number of
      glomeruli in the rabbit's kidney open to the circulation under the chosen
      experimental conditions without intentional interference, indicate the "normal"
      range to be from 42 to 100 per cent. Since ten of the thirteen results fall
      within the figures 56 and 89 per cent, we may take these figures as the chief
      basis for our discussion. Three experiments only were made in which renal
      vasodilatation was produced by caffeine and salt. The percentage of open
      glomeruli found was in every case higher than any control except one. The results
      show without ambiguity that in rabbits, as in frogs, renal vasodilatation by
      caffeine is accompanied by increase in number of patent glomeruli. Our prime
      interest lay in the general question rather than in the action of individual
      substances in the group of vasodilators; hence this series was not extended
      further. Among the experiments designed to test the effects of renal
      vasoconstriction are to be found nine in which adrenalin was injected, two in
      which CO(2) was inhaled, two in which the splanchnic nerve was stimulated, and
      four in which hemorrhage was induced. Not all are of equal value for our present
      purpose, inasmuch as the degree of certainty with which we can assume that renal
      vasoconstriction was actually produced is not the same in all. Enough experience
      with the action of adrenalin on the kidney of the anesthetized rabbit is
      available to permit the assertion that the dosages used in the nine adrenalin
      experiments were sufficient to insure constriction of renal vessels. Similar
      certainty exists in the experiment in which high concentration of CO(2) was used;
      less in the case of 10 per cent CO(2). Stimulation of the splanchnic nerve in
      rabbits so frequently fails to produce results typical of direct constriction of
      renal vessels that we may regard the production of this effect in the two
      experiments in which this was done as doubtful. In the perfusion experiments by
      Richards and Plant (7) the reactions of the renal vessels to stimulation of the
      splanchnic nerve resembled those to intravenously injected adrenalin rather than
      to the direct excitation of constrictor fibers. In six rabbits in which
      Livingston subjected the nerve to varying degrees of electrical stimulation, in
      one only was distinct constriction of the renal vessels produced, and in this a
      latent period of 45 seconds occurred between the beginning of stimulation and the
      production of effect. In one of our experiments a rabbit was used in which the
      superior cervical sympathetic ganglion on the left side had been extirpated
      months before. During the stimulation of the splanchnic nerve the left pupil was
      observed to dilate, showing increased adrenalin secretion. Hence, we are inclined
      to regard the two attempts to produce vasoconstriction by this means as having
      been largely unsuccessful. In one experiment only of the four in which hemorrhage
      was induced was there unmistakable evidence of compensatory vasoconstriction
      which may have involved the renal vessels. The blood pressure curve of this
      animal showed rhythmically occurring waves of the Traube-Hering type and dyspnea
      was noted. In this the estimate of open glomeruli was 28 per cent. In the other
      three experiments no such change occurred and no dyspnea was seen. In pithed
      frogs, hemorrhage alone of moderate extent is less apt to lessen the number of
      patent glomeruli than are any of the other constrictor agencies tried by Richards
      and Schmidt. In this discussion, therefore, we lay little weight on the results
      obtained in the two experiments in which the splanchnic nerve was stimulated and
      on those of the first three hemorrhage experiments. The chief conclusion to be
      drawn from these experiments is that which was anticipated from the observations
      of Richards and Schmidt on frogs, and of Khanolkar on rabbits; viz., that in the
      rabbit, renal vasodilatation and renal vasoconstriction are usually associated
      with increase and decrease respectively in number of glomeruli through which
      blood flows (see Text-fig. 1). Analogous changes apparently occur in the
      capillary pathway in individual glomeruli. Hence renal function in mammals may be
      altered by changes in the extent of glomerular filtration surface to which the
      blood has access. Other conditions remaining the same, it is obvious that changes
      in extent of filtration surface must result in proportionate changes in urinary
      output. The figures for rate of urine elimination at the time of injection of the
      dye in these experiments are in substantial agreement with these statements (see
      Text-fig. 2). Exceptions to our chief conclusion as stated have been encountered.
      In Experiment 57,86 per cent of the glomeruli were open in a constricted kidney
      which was excreting no urine: in Experiment 30, 16 per cent were open in the
      kidney which was eliminating seven drops per minute: the outputs of the kidneys
      in the caffeine experiments were far higher than those of control kidneys in
      which comparable numbers of glomeruli were open. In considering these exceptions,
      account must be taken of the fact that other conditions do not commonly remain
      constant. When a renal vasodilator is introduced we conceive not only of possible
      increase in extent of accessible glomerular surface, but also of increase in
      glomerular pressure and increased rate of renewal of fluid in contact with
      glomerular membranes. Hence the response is greater than can be accounted for by
      any one factor alone. A basis of experiment exists in support of the belief that
      usually sufficient differences in physiological state exist among the small
      arteries and arterioles of the kidney so that a constrictor influence, exerted
      equally upon all, elicits various degrees of response (1). Closure of some,
      continuing patency of others, results. Blood flow and blood pressure in the
      glomeruli which are supplied by the vessels which remain open may be decreased,
      increased, or unchanged according See PDF for Structure. to the relation between
      the degree of reaction in those vessels and the height of arterial blood
      pressure. It is not to be expected that urinary outputs will uniformly vary with
      the number of glomeruli remaining open. Rapid blood flow and high glomerular
      pressure in relatively few glomeruli may result in more urine than slow flow and
      low pressure in many. This argument is implicit in Hermann's original statement
      and is completely in harmony with the result of direct observation in the frog.
      It is supported by the data of Experiment 30. In Experiment 57, however, urine
      was suppressed by adrenalin when 86 per cent of the glomeruli remained open. The
      kidney in this experiment was highly diuretic before the adrenalin injection. We
      may, therefore, assume that all or nearly all of the glomeruli were open and that
      intermittent contractions of the arterioles were minimal; hence, that the
      physiological state of the vessels concerned was more nearly uniform than is
      conceived to be the case when only a fraction of the glomeruli are open and in
      which intermittent contractions and relaxations must be pronounced. Thus a
      relatively uniform constriction was produced in all of such degree as to lessen
      materially glomerular pressure and blood flow, but insufficient to actually close
      more than a few afferent arterioles. In Experiment 33, the dosage of adrenalin
      was such as to permit the possibility that constrictor action may have been
      largely confined to efferent vessels (8). While the exceptional results have been
      discussed at greater length than has been devoted to the majority of experiments,
      we believe that they do not constitute adequate ground for criticism of the chief
      conclusion as stated.

PMID- 19869080
TI  - THE PHYSIOLOGICAL RESPONSE OF THE CIRCULATORY SYSTEM TO EXPERIMENTAL ALTERATIONS
      : I. THE EFFECT OF INTRACARDIAC FISTULAE.
AB  - An abnormal communication, experimentally produced between the right and left
      ventricles, causes a deflection of part of the blood stream into the shorter
      pulmonary circuit. Proceeding pari passu with the increase in volume flow of
      blood through this shorter circuit, there occurs a gradual enlargement of the
      heart limited to that part of the circulatory system through which the deflected
      blood passes; namely, the left ventricle, the right ventricle, the pulmonary
      artery, and the left auricle. There is also a demonstrable hypertrophy of the
      right and left ventricles, which presumably is the result of the increased effort
      necessary to propel forward an increased volume flow of blood, since it cannot be
      attributed to an increased peripheral resistance. Immediately after the
      production of the defect, the right auricle and aorta become smaller than usual,
      conforming in size to the decreased volume flow of blood through them. As full
      compensation for the deflected flow occurs by an increase in total blood volume,
      they return to their normal size. If full compensation has not occurred they
      remain smaller than normal (Dog X 11). The changes incident to the establishment
      of an opening in the septum are entirely dependent upon the size of the defect,
      and hence, upon the extent of the volume of blood deflected into the shorter
      circuit. Commensurate with the volume of blood deflected, there is a fall in
      general blood pressure. If the animal survives the immediate fall in blood
      pressure, certain compensatory adjustments occur which reestablish a more normal
      blood pressure: (a) an immediate increase in pulse rate; (b) a gradual increase
      in total blood mass. The increase in blood volume is directly commensurate with
      the size of the defect. The pulse returns to a normal rate when complete
      compensation through an increase in blood volume has been attained. It is
      suggested that the enlargement of the heart seen clinically in so called
      "idiopathic hypertrophy," "essential hypertension," and also in certain cases of
      cardiorenal disease, may be due to an increase in total blood mass following some
      interference with the mechanism for its control. The seat of this impairment in
      blood volume control may be: (a) in a chemical alteration in the blood; (b) in a
      diseased function of the kidneys which may be responsible for a decreased
      elimination, or for a change in the chemical composition of the blood; or (c) in
      an abnormal stimulation of the organs producing the cellular elements of the
      blood.

PMID- 19869081
TI  - THE PHYSIOLOGICAL RESPONSE OF THE CIRCULATORY SYSTEM TO EXPERIMENTAL ALTERATIONS
      : II. THE EFFECT OF VARIATIONS IN TOTAL BLOOD VOLUME.
AB  - The pericardium presents a limiting or constricting action to acute dilatation of
      the heart. The diastolic pressure tends to approach the systolic pressure in a
      circulatory system distended with blood. The limiting action of the pericardium
      may be responsible for the small differences in the size of the heart noted by
      Meek and Eyster in their studies on the effect of plethora. The views concerning
      the function of the pericardium are divergent. That it may restrict the heart in
      cases of acute dilatation is shown in the above experiments. If the tension upon
      the pericardium be exerted over a prolonged period of time, as occurs in cases of
      pericardial effusion, the pericardium readily enlarges. If, however, the
      intrapericardial pressure should at any time equal the pressure in the venae
      cavae, blood would no longer enter the heart and the condition would become
      fatal. In recovery experiments, pericardiectomy was followed by no demonstrable
      effect upon the general health of the dog, upon the response to exercise, or upon
      the size of the heart (6).

PMID- 19869082
TI  - PRIMARY LUNG TUMORS IN MICE FOLLOWING THE CUTANEOUS APPLICATION OF COAL TAR.
AB  - The external application of tar to a number of separated areas on the surface of
      mice, in such fashion that no single area is irritated sufficiently long to cause
      lesions of the skin, has resulted in a very high incidence of lung tumors. This
      incidence ranged from 60.0 per cent in one experiment to 78.3 per cent in
      another. Control mice from the same stock but from 3 to 6 months older, and for
      that reason the more liable to spontaneous lung tumors, failed to show a single
      instance of such growths. Even in a stock in which spontaneous lung tumors had
      been frequent, the incidence for corresponding age periods has never been above
      5.5 per cent while the average has been between 1 and 2 per cent over a period of
      years. The tumors in the tar-painted animals occur as small white nodules, either
      single or multiple. They are typical epithelial neoplasms, identical
      histologically with those described by previous authors as occurring
      spontaneously in mice. Some possible factors in the causation of the tumors are
      briefly discussed.

PMID- 19869083
TI  - THE SOLUBLE SPECIFIC SUBSTANCE OF A STRAIN OF FRIEDLANDER'S BACILLUS : PAPER I.
AB  - 1. A method is given for the isolation of a specifically reacting nitrogen-free
      polysaccharide from the so called E strain of Friedlander's bacillus. 2. The
      properties of this polysaccharide are described.

PMID- 19869084
TI  - THE SOLUBLE SPECIFIC SUBSTANCE OF FRIEDLANDER'S BACILLUS : PAPER II. CHEMICAL AND
      IMMUNOLOGICAL RELATIONSHIPS OF PNEUMOCOCCUS TYPE II AND OF A STRAIN OF
      FRIEDLANDER'S BACILLUS.
AB  - The chemical and immunological properties of the soluble specific substances of a
      strain of Friedlander's bacillus and Pneumococcus Type II are described and
      correlated, and the serological and antigenic similarity of these biologically
      unrelated organisms is discussed as an example of heterogenetic specificity among
      bacteria.

PMID- 19869085
TI  - THE SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS : THIRD PAPER.
AB  - 1. Refinements in the methods for the isolation of the soluble specific
      substances of Types II and III pneumococcus are described. These improvements
      have resulted in the isolation of the end-products in a form free from nitrogen
      and of enhanced activity with immune serum. 2. The soluble specific substance of
      Type I pneumococcus is described and shown to differ sharply from the
      corresponding substances of the other two types, each of which, in turn, differs
      from the other. 3. Progress is reported on the identification of the sugar units
      from which the polysaccharides are built up. 4. The evidence so far accumulated
      is believed to favor strongly the view that the polysaccharides isolated are the
      actual specific substances of Pneumococcus.

PMID- 19869086
TI  - THE IMMUNIZING ANTIGEN OF THE PNEUMOCOCCUS : III. THE PURIFICATION OF THE WATER
      SOLUBLE ANTIGEN.
AB  - Actively immunizing fractions of protein nature have been isolated from broth
      culture filtrates of Pneumococcus Type I by ultrafiltration, precipitation at a
      definite hydrion concentration, and the separation of a soluble picrate fraction.
      The method appears to be suitable for the initial purification of this antigen.

PMID- 19869087
TI  - TISSUE CHANGES FOLLOWING DEPRIVATION OF FAT-SOLUBLE A VITAMIN.
AB  - The specific tissue changes which follow the deprivation of fat-soluble vitamin A
      in albino white rats and in the human concerns epithelial tissues. This effect is
      the substitution of stratified keratinizing epithelium for normal epithelium in
      various parts of the respiratory tract, alimentary tract, eyes, and paraocular
      glands and the genitourinary tract. We have described the morphological sequences
      which clearly show that the replacement of epithelium arises from focal
      proliferation of cells arising from the original epithelium and not by
      differentiation or change of preexisting cells. Young rats respond to the
      deficiency more promptly than adults. Growth activity of epithelium is not
      diminished. On the contrary, there is convincing evidence that it is greatly
      augmented. In a few of our animals the behavior of the replacing epithelium in
      respect to numbers of mitotic figures and response on the part of connective
      tissue and blood vessels suggests the acquisition of neoplastic properties. While
      the epitheliums which are the seats of these changes are largely of covering
      types, glandular epithelium is involved, specifically in the paraocular glands
      and salivary glands. It is highly probable also that the epithelium of gland
      ducts, respiratory mucosa, and genitourinary tract have secretory functions so
      that we conclude that the deficiency results in loss of specific (chemical)
      functions of the epitheliums concerned, while the power of growth becomes
      augmented. Explanation for the substitution of a chemically inactive
      (nonsecretory) epithelium, common in type for all locations, remains a matter of
      speculation. We can only speculate also in regard to the absence of change in the
      epithelium of such organ as the liver, parenchyma of the kidney, stomach, and
      intestines. The significance of the order or sequence in which different organs
      exhibit this change has not been determined. In general the respiratory mucosa in
      nares, trachea, and bronchi respond first, then the salivary glands, eye,
      genitourinary tract, then paraocular glands and pancreas, although as has been
      noted there are exceptions to this order. Our studies show that the mitochondrial
      apparatus is not primarily affected. Study of individual cells indicates that the
      first morphological evidence of avitaminosis will be found in the nucleus. We
      have not devoted sufficient study to be certain, but an increase of chromatin and
      in some instances in size of nucleoli are early morphological manifestations.
      Other important effects of fat-soluble A deficiency are atrophy of glandular
      organs, emaciation, localized edema of testes, submaxillary gland, and connective
      tissue structures of the lungs and focal myocardial lesions. From our own limited
      experience with rats fed on a water-soluble B deficient diet and from work by
      Cramer, Drew, and Mottram, the loss of fat in water-soluble B deficiency is as
      great, if not greater than in vitamin A deuciency, so that tor tne present we
      assume that this is not a specific manifestation of any one avitaminosis. The
      same applies to glandular atrophy. Both of these effects probably concern the
      nutrition as a whole and may be ascribed to inanition. The occurrence of
      transient edema in testes and salivary gland coinciding with a period of maximum
      atrophic change, suggests the hypothesis that this edema is the result of failure
      of epithelium to utilize transported material, which leads further to the
      hypothesis that the capillaries of these organs are differentiated in regard to
      permeability to the respective materials utilized by the cells. It would seem
      that in the case of the testis we have a unique instance of complete atrophy
      producible at will without impairment of circulation and supporting tissues. This
      phenomenon may possibly be followed with advantage in the study of the mechanism
      of edema. Vascularization of the cornea, as we have shown it to be independent of
      infection, must be a physiological response to the increased demands of the
      rapidly growing epithelium which has replaced the corneal epithelium. We have
      assumed throughout this work that the diet on which we kept our animals was
      deficient in respect to a single substance or group of substances having similar
      physiological properties, designated by the term fat-soluble vitamin A. Whether
      or not more than one so called vitamin or accessory substance was missing in the
      diet we employed does not affect the theoretical importance of the morphological
      results. Work by Evans and Bishop would indicate that other factors affecting
      fertility in addition to the so called antixerophthalmic or vitamin A factor may
      have been missing. Our own experience leads us to believe the specific effects we
      have described upon epithelial tissues were in all probability due to withdrawal
      of a single factor. We have shown how these effects, that is the replacement of
      uterine epithelium by keratinizing epithelium can account for sterility in the
      female. Whether or not the atrophy of the testis is due to the same factor
      remains to be proved, but presumptive evidence is strong that this is the case.
      The study of the reverse changes that follow in the rapid amelioration when the
      rats are restored to an adequate diet has been begun and will be reported later.
      We have shown that the substitution of keratinizing epithelium in all locations
      is not secondary to infections, and presumably is a primary effect of the
      withdrawal of factors essential for the chemical activities or maintenance of
      differentiation of the epitheliums concerned. It is, of course, possible that the
      phenomenon is produced in a roundabout way in that it may be secondary to the
      effects of the avitaminosis upon the metabolism of tissue-sustaining substances.
      This possibility is supported by the cessation of growth of the skeleton and
      teeth, although we know that other avitaminoses produce retardation of growth.

PMID- 19869088
TI  - THE ALVEOLAR PORES OF PNEUMONIA.
AB  - Evidence is seen in Fig. 1 that the alveoli are lined with a continuous
      epithelium. In Fig. 2 there has been extensive shedding of the epithelium and
      broad sheets of fibrin are attached to the alveolar wall. On the right the
      exudate has escaped from both sides of the alveolar wall and the network of
      fibrin has begun to appear beneath the epithelium on its upper side. Owing,
      however, to the fact that the epithelium is still intact, though slightly raised
      from the surface, no pore has been formed. In Fig. 3 the exudate has found its
      exit from a very definite point and has been converted into fibrin which radiates
      into the alveolus. No pore has resulted because the epithelium on the opposite
      side of the alveolus is still intact. In Fig. 4 the epithelium has been pushed
      off from diametrically opposite sides of the alveolar wall and a pore has been
      formed with a thread of fibrin passing from one alveolus to an adjoining
      alveolus. Pores are as numerous in edema due to mitral stenosis with in
      sufficiency of the valves as in pneumonia, but there are no threads of fibrin to
      direct attention to them. This study confirms my previously expressed opinion
      pores are not normal, preformed openings.

PMID- 19869089
TI  - SKIN REACTIONS TO ALTERNATE HEAT AND X-RAY EXPOSURES.
AB  - Different areas on the abdomen of the same guinea pigs have been exposed to
      suberythema doses of soft x-rays, to heat of an intensity below the critical dose
      for the production of burns, and to both radiations in sequence. The only effect
      of exposure to x-ray or heat alone was a slight scaling of the skin. The areas
      exposed to heat and x-radiation developed well marked and persistent burns. The
      results were the same no matter in which sequence the agents were applied.

PMID- 19869090
TI  - STUDIES ON EXPERIMENTAL RICKETS : I. THE OCCURRENCE OF RICKETS IN YOUNG RABBITS
      BORN OF MOTHERS INFECTED WITH SCHISTOSOMUM JAPONICUM.
AB  - Our observations show that young rabbits born of mothers afflicted with
      Schistosomum japonicum develop typical rickets. Rickets can also be produced if
      we infect the young, healthy rabbits with the same parasite. It is natural to
      suppose that the rachitic changes are caused by the parasite itself. Since,
      however, a similar disease can be produced in the offspring, when the mother is
      fed on egg yolk, the causation is not limited to the action of this parasitic
      toxin alone. The toxin of Schistosoma may disturb the calcium and phosphorus
      metabolism of bone in young animals, especially in the period of vigorous growth;
      that is, 20 to 40 days after birth of the rabbits. Or it may exhaust some element
      important in the calcium and phosphorus metabolism such as vitamin A or D. The
      fact that exhaustion of the antirachitic factor in the mother causes rickets in
      the young, as Grant (1924) showed, and that certain low grade infections can
      exhaust vitamin B as shown by Wedgewood (1924), is in line with this conception.
      It may be added here that most investigations on rickets have been carried out on
      rats and dogs. We have found a simple and excellent way of producing rickets in
      rabbits by dietary deficiency. Concerning this method, we shall report elsewhere.

PMID- 19869091
TI  - THE PROBLEM OF THE ETIOLOGY OF HERPES ZOSTER.
AB  - Attempts were made to produce lesions in. animals by the injection of material
      obtained from the vesicles and involved skin of nine cases of herpes zoster. All
      the cases, with the exception of one (Case II), were characteristic cases of
      idiopathic herpes zoster and the question of their being cases of so called
      zosteriform herpes or symptomatic herpes zoster can hardly be raised. As regards
      Case II, if this case occurred alone, there might be some doubt as to its nature
      on account of the mildness of the symptoms and the small area of skin
      involvement. Taken in connection with Cases III and IV, however, which occurred
      in the same ward and in patients who were quite closely in contact with Patient
      II, it seems fairly reasonable to assume that they were all of the same
      character. Cases of herpes zoster have been extremely rare in this hospital and
      the occurrence of three cases in the same ward within a very short period of time
      suggests very strongly a transference of infection from one case to the other.
      That Case II was not one of herpes simplex also seems fairly certain from the
      negative results obtained by inoculation of rabbits' eyes with vesicle material.
      In making the animal experiments we employed various methods which were suggested
      largely by the technique used by previous observers, especially by those who have
      reported results which were considered positive. In making inoculations into the
      corneas the technique recommended by Lipschutz was employed as far as possible.
      Young rabbits were used and the material was obtained from fresh vesicles early
      in the disease and inoculated with as little delay as possible. The material
      injected into rabbits' eyes was obtained from seven cases and twenty-four rabbits
      were used. In judging of the results obtained in this kind of experimentation
      great caution must be observed. Our experience convinces us that slight opacities
      occurring along the lines of scarification and mild conjunctivitis cannot be held
      to indicate the effect of a specific virus. As regards the interpretation of the
      microscopic changes found, we were quite familiar with the appearance of
      intranuclear inclusion bodies as seen in the lesions of experimental herpes
      simplex and the filterable virus (Virus III) indigenous to rabbits described by
      Rivers and Tillett (5). We also had no difficulty in imding intranuclear
      inclusions in the sections of skin removed from patients. It is not likely,
      therefore, that these structures were overlooked in our study of the sections.
      Briefly stated, although the material studied was satisfactory and in spite of
      the fact that a considerable number of animals were used for each case, we have
      been unable to confirm the observations of Lipschutz regarding the experimental
      production of specific lesions in the corneas of rabbits. We realize that this is
      only negative evidence and therefore not of conclusive importance in view of
      Lipschutz's observations. It indicates, however, that the production of specific
      lesions in rabbits' eyes with material from herpes zoster vesicles is extremely
      difficult and that successful results may be a matter of chance, depending,
      possibly, on peculiar susceptibility on the part of the rabbits. In view of the
      fact, however, that a careful analysis of the positive results reported by other
      observers shows that the conclusions were based on insufficient evidence, we
      believe that further work is necessary before the successful inoculation of the
      rabbits' corneas with herpes zoster virus can be accepted as fully demonstrated.
      To make the evidence convincing specific lesions should be obtained with a fair
      degree of regularity and the virus should be successfully transmitted through at
      least two generations. Apparently the latter was not attempted by Lipschutz.
      Intracerebral inoculations into three rabbits with material from two cases (Nos.
      I and IV) were made. Two rabbits were also inoculated intraspinally with material
      from one case (No. IV). None of these animals showed any reaction. In the case of
      one of the animals inoculated into the brain (Case I) although this rabbit showed
      no symptoms, we thought it conceivable that the susceptibility of the species for
      the virus might be so slight that no obvious lesion had been produced.
      Nevertheless it was thought that the virus might possibly remain alive at the
      seat of inoculation and by repeated transfers become adapted to the rabbit. This
      phenomenon has been observed by Noguchi with vaccine virus, and by Rivers and
      Tillett with the rabbit virus isolated by these workers. This possibility was
      tested by us by making serial corneal and brain inoculations. Corneal transfers
      were carried through fourteen animals in series, and brain transfers through ten.
      No specific lesions developed in any of the animals. The work of Teague and
      Goodpasture suggested that the skin might be rendered more susceptible to
      infection by previous treatment with tar. Material from two cases (Nos. I and
      VIII) was inoculated into the tarred skin of guinea pigs and rabbits. The
      material was injected intracutaneously and also rubbed into the scarified skin.
      No reaction was obtained in any of the animals. Finally, the transmission of
      herpes zoster to monkeys was attempted. Blanc and Caminopetros, and Bastai and
      Busacca, as discussed in the review of the literature, inoculated monkeys
      (Macacus) in various ways, without success. It was thought possible that although
      monkeys of the genus Macacus might be refractory, monkeys of another genus might
      prove susceptible. Consequently, besides the inoculation of two Macacus monkeys,
      attempts were made to infect five vervets. Moreover, in view of the fact that the
      virus of vaccinia and the rabbit virus of Rivers and Tillett could be
      successfully cultivated in the testicle, intratesticular inoculations were
      employed. The testicles were removed at varying periods following inoculation.
      Numerous sections of these testicles were made and examined, but in no instance
      were any lesions found which could be interpreted as specific. No cells
      containing intranuclear inclusion bodies were found. These experiments,
      therefore, have also led to purely negative results. This report of our work is
      made at the present time because a considerable amount of literature has been
      published which gives the impression that herpes zoster has been successfully
      transmitted to animals. Although the observations of Lipschutz are suggestive, it
      is important that they be confirmed by further investigations. Until herpes
      zoster can be regularly transmitted to animals and cross-immunity tests be
      carried out, the relation of the virus of herpes zoster to that of herpes simplex
      remains a matter of speculation. In view of the fact that herpes simplex can be
      easily and regularly transmitted to rabbits, whereas in the hands of a large
      number of investigators similar experiments with herpes zoster are completely
      negative, it does not seem likely that the etiological agent concerned in these
      two diseases can be absolutely identical. The question of the identity or non
      identity of herpes zoster and varicella is even more difficult to answer, because
      at present neither of these infections is readily transmissible to animals. The
      work of Kundratitz is extremely interesting. His observations, aside from
      indicating a close immunological relationship between herpes zoster and
      varicella, are important in that they seem to show the presence of a
      transmissible virus in the vesicles of herpes zoster. The only question that
      arises is whether the cases of herpes zoster from which Kundratitz was able to
      make successful transfers were true cases of idiopathic herpes zoster.

PMID- 19869092
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : IV. CONCERNING THE ONENESS OF THE
      BACTERIOPHAGE.
AB  - Lytic filtrates, active against Bacillus dysenterioe Shiga, Bacillus coli,
      Bacillus pestis cavioe, and staphylococcus respectively, proved to be differently
      affected by changes in hydrogen ion concentration. Anti-staphylococcus lysin was
      the least resistant of the four, showing deterioration in 3 hours at 7 degrees C.
      beyond the zone of hydrogen ion concentration limited by C(H) = 6.3 x 10(-5) and
      C(H) = 1.6 x 10(-9). Under the same conditions, the zone of resistance of anti
      coli filtrate lay between C(H) = 2.7 x 10(-3) and C(H) = 2.5 x 10(-11), and that
      of anti-Shiga between C(H) = 1-7 x 10(-4) and C(H) = 1-3 x 10(-11). Anti-pestis
      cavioe filtrate was most resistant of the four, retaining its full activity in
      the zone from C(H) = 1 x 10(-3) to C(H) = 3.5 x 10(-12). The fact that these
      differences in individual resistance persisted, notwithstanding the repeated
      passage of lytic filtrates through cultures of bacteria other than those against
      which they were primarily active, seems to offer evidence in favor of a
      multiplicity of bacteriophages.

PMID- 19869093
TI  - STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY : II. THE
      INCIDENCE OF TAR TUMORS IN STRAINS OF MICE HAVING A DIFFERING INCIDENCE OF
      SPONTANEOUS GROWTHS.
AB  - 1. Two strains of mice, one with a high, the other with a comparatively low
      incidence of spontaneous tumors of the mammary gland, when painted between the
      shoulders with coal tar extract developed tar tumors with about practically
      identical frequency. Possibly this result was to have been expected. If tumors of
      certain organs or tissues are specific in heredity, a conception for which there
      is some evidence, then assuredly a high degree of incidence for one tissue, as
      for example the mammary gland, does not necessarily mean a high incidence for
      another tissue, such as the skin, when subjected to tarring. To test the
      influence of heredity on the response of the skin to tar painting it would be
      best to employ strains of animals exhibiting differences in the incidence of
      spontaneous cancer of the skin. Unfortunately no such material was available. We
      can state on the basis of our experiments only that no hereditary differences in
      the response of the skin to tar painting were demonstrable in two strains of mice
      manifesting markedly different percentage incidences for spontaneous mammary
      growths. It is possible, of course, that the natural differences in the two
      strains may have been wiped out by the tar treatment. Such a view is suggested by
      the result of other work in this laboratory which has shown that tar painting
      increases markedly the incidence of tumors of the lung and destroys the
      resistance to transplantable tumors (unpublished work). 2. Mice from which
      spontaneous mammary tumors had been removed were treated with tar. The percentage
      incidence of the resulting tar tumors was similar to that met with in the
      controls, except possibly in the case of such animals as showed a recurrence of
      the spontaneous growth. In them the development of tar tumors seemed to be
      delayed and possibly prevented. The numbers involved are too small to be
      conclusive. Murray has stated that "the induction of a fresh primary growth after
      a first has been definitely established, meets with a very intense resistance
      whether the first tumor be of the same parent tissue or another." His condusions
      are based partly upon certain retarring experiments but more especially upon a
      series of mice from which spontaneous mammary gland tumors had been removed,
      which were then tarred. Apparently these latter did not have recurrences of the
      spontaneous growth. Only 1 of them developed a papilloma and none carcinoma. The
      tar was applied twice weekly in Murray's experiment instead of 3 times as in ours
      and for this as for many other reasons a direct comparison is not possible. It is
      furthermore not clear what the expectation for his group would have been. Our
      conclusions, however, seem only partly to confirm his for we find that if any
      protection exists against a tar cancer after the ablation of a spontaneous
      mammary growth, it is only when a recurrence has taken place. From certain
      additional tarring experiments Murray concluded that if a second tarring is begun
      before cancer has developed from the first, susceptibility is increased. Truffi
      also has found a diminished refractoriness after tarring. Among our mice in which
      the mammary gland recurrence appeared during or after the tar painting, no
      increase in susceptibility but rather the reverse was found. Future
      experimentation must determine to which among several variables this divergence
      of results is to be attributed.

PMID- 19869094
TI  - SEROLOGICAL STUDIES ON THE BLOOD OF THE PRIMATES : I. THE DIFFERENTIATION OF
      HUMAN AND ANTHROPOID BLOODS.
AB  - While the precipitin tests do not differentiate, according to the results of
      previous workers, between the serum proteins of man and chimpanzee, a clear-cut
      differentiation between the blood cells of man and the anthropoids was obtained
      by means of hemagglutinins. According to our tests on bloods of whites and
      negroes, constant racial serological differences among human bloods, if they
      exist at all, are certainly smaller than the differences between the bloods of
      man and the anthropoid apes. The serological differences between man and the
      lower monkeys appear to be no greater than those between the anthropoid apes and
      the lower monkeys. These findings confirm the opinion that the anthropoid apes do
      not rank in the genealogical tree between lower monkeys and man.

PMID- 19869095
TI  - SEROLOGICAL STUDIES ON THE BLOOD OF THE PRIMATES : II. THE BLOOD GROUPS IN
      ANTHROPOID APES.
AB  - The bloods of twenty-one anthropoid apes have been examined serologically. It was
      found possible to assign each to one of the four human blood groups. The
      isoagglutinogens of the anthropoids were found to be identical with those of
      human blood. These very same factors could not be demonstrated in the blood of
      the lower monkeys. In the blood of the fourteen chimpanzees examined only the
      isoagglutinogen A has been found, whereas both A and B were present in the blood
      of the six orangs. The significance of these findings for the knowledge of the
      human blood groups is discussed.

PMID- 19869096
TI  - SEROLOGICAL STUDIES ON THE BLOOD OF THE PRIMATES : III. DISTRIBUTION OF
      SEROLOGICAL FACTORS RELATED TO HUMAN ISOAGGLUTINOGENS IN THE BLOOD OF LOWER
      MONKEYS.
AB  - Serological studies on the bloods of thirty-six species of lower monkeys have
      shown that there exists a correspondence between the distribution of a certain
      hemagglutinogen and the place of the species in the zoological system. In twelve
      species of seven genera of Platyrrhina (New World monkeys) and six species of the
      genus Lemur a factor similar to the human isoagglutinogen B was present; in
      eighteen species of four genera of Cercopithecidae (Old World monkeys) it was
      absent, although the latter are more closely related to man than the former. It
      would seem from our findings that a genus, perhaps even a family, of animals may
      be characterized by a special serological factor. The factor found in the lower
      monkeys is not identical with the one existing in the erythrocytes of the
      anthropoid apes and man.

PMID- 19869097
TI  - STUDIES OF LEPTOSPIRA HEBDOMADIS.
AB  - From the results of etiological study of the disease known as akiyami which
      prevails in the Shida district of Shizuoka province, we conclude that: 1. Akiyami
      is an infectious disease caused by a leptospira. 2. The leptospira causing
      akiyami is very difficult to differentiate morphologically from Leptospira
      icterohoemorrhagioe and Leptospira hebdomadis. 3. The strains of leptospira
      isolated from cases of akiyami are of two types. One type, isolated from three of
      the sixteen cases, is highly virulent for guinea pigs and is serologically
      distinct from Leptospira icterohoemorrhagioe and Leptospira hebdomadis; we have
      called this the A type. The type obtained from the other cases is less virulent
      for guinea pigs and is serologically identical with Leptospira hebdomadis; we
      have called this the B type. 4. The field mouse (Microtus montebelli), which
      harbors Leptospira hebdomadis, has also been found to harbor the A type of
      akiyami.

PMID- 19869098
TI  - THE INFLUENCE OF HIGH PROTEIN DIET ON THE KIDNEYS.
AB  - Seven groups of rats were fed on diets containing protein varying in amount from
      1.36 to 40.13 per cent derived mainly from grain, casein, meat, and milk with
      carbohydrate, fat, and vitamines. From a number of animals one kidney was removed
      to double the load on the remaining one. The time of feeding was from 9 weeks to
      6 months. Blood uric acid, blood urea nitrogen determinations, and microscopic
      examinations of the kidneys revealed no evidence of kidney damage. There was
      evidence of kidney hypertrophy consisting of increased weight of the kidney,
      large diameters of the capillary tufts, convoluted tubules, and kidneys in the
      animals receiving high protein diet. The nephrectomized animals that ate high
      protein had no kidney changes save hypertrophy and this amounted to an increase
      in weight of an average of 0.54 gm. or 85 per cent of the average weight of the
      right kidneys of the controls.

PMID- 19869099
TI  - A CHEMICAL STUDY OF THE SPECIFIC ELEMENTS OF TUBERCULIN. I.
AB  - 1. The specific precipitin reaction and the skin reaction given by old tuberculin
      are attributable to two separate substances present in this material. The cause
      of the reaction first mentioned is a non-protein gum which will be fully
      described in the following paper. The cause of the skin reaction is probably but
      not surely a protein. 2. Methods which have been suggested for the
      standardization of tuberculin by precipitin or complement fixation reactions
      should be revised.

PMID- 19869100
TI  - SEROLOGICAL RELATIONSHIPS OF TYPE-SPECIFIC AND DEGRADED PNEUMOCOCCI.
AB  - 1. Immune sera prepared with the degraded or variant forms of pneumococci (R
      strains) are similar in their reactions to sera prepared with the protein or cell
      solutions of pneumococci. They contain antibodies reactive with the protein of
      all types of pneumococci, but no antibodies reactive with the type-specific
      substances. 2. Pneumococci of the variant or R form, regardless of type
      derivation, are serologically identical and have the antigenic characteristics of
      pneumococcus protein. They evoke the species-specific and not the type-specific
      antibodies. 3. Antipneumococcus sera obtained by immunization with S strains may
      contain species-specific antibodies in addition to those which are type-specific.
      Each kind of antibody can be removed separately from these sera by selective
      absorption with the R or S strains of pneumococci.

PMID- 19869101
TI  - THYMECTOMY IN THE RABBIT.
AB  - Thymectomy in the rabbit is a comparatively simple procedure. The open method
      described above offers many advantages over any of the closed methods and success
      depends largely upon the observance of a few precautions; chief among these is
      the avoidance of haste and the observance of aseptic technique. The operative
      mortality in our series of rabbits was 10 per cent and there was an additional
      loss of useful animals, due to secondary complications, amounting to 16 per cent.
      Among the last 29 rabbits, however, there was only 1 operative death, in an old
      animal, and 2 cases of slight infection. It appears, therefore, that with some
      experience the operation can be carried out successfully in nearly all animals,
      especially so if comparatively young rabbits are used. Old rabbits present
      greater difficulties on account of the presence of dense fibrous tissue within
      the field of operation. While the animals of this series showed no immediate
      symptoms or alteration in physical condition that could be referred to
      thymoprivia, it is not to be assumed that removal of the thymus is entirely
      without effect even on rabbits of mature age. Our observations on the reaction of
      thymoprivic rabbits to disease show that this is not the case and that in all
      probability decided effects can be demonstrated if the problem is approached on
      another basis. The object of the present investigation was, however, to determine
      whether the thymus could be completely removed from rabbits of certain ages
      without producing any serious disturbance of health which would interfere with
      their use in other experiments or complicate the interpretation of results. It
      was found that this could be done.

PMID- 19869102
TI  - ON THE SURFACE COMPOSITION OF NORMAL AND SENSITIZED MAMMALIAN BLOOD CELLS.
AB  - The interfacial tension method has been applied to the study of the surface
      composition of mammalian blood cells and to certain other particles. Unsensitized
      erythrocytes and stromata possess only a small margin of stability in the
      interface and pass readily into the oil phase. Specifically sensitized
      erythrocytes and stromata possess much greater stability in the interface and
      pass into the oil only with considerable mechanical aid; characteristic
      deformations of the erythrocyte surface or the interface or both often result.
      With special immune sera prepared by Landsteiner and van der Scheer the
      quantitative relations are such as to indicate that the increased polarity of the
      sensitized erythrocyte surface is due to combination of the red cell surface
      lipoids with hemolytic sensitizer. These results are corroborative of the
      conclusion of Landsteiner and van der Scheer that erythrocytes contain specific
      lipoid-soluble antigens. The tentative conclusion is reached that with these anti
      horse-erythrocyte sera at least the agglutinins combine predominantly with the
      protein of the red cell surfaces. Fresh human leucocytes are spread and
      disintegrated by the interfacial stresses. After heat injury over the condenser
      with substage lamp the leucocytes typically do not enter the boundary surface.
      They are pushed before the advancing interface and, if their further advance is
      obstructed, bend the interface backward to form peninsulas and vacuoles. This
      change after heating is in the opposite sense to that to be expected from
      denaturation of the proteins of the protoplasm. Fresh oxalated rabbit platelets
      pass very easily into the oils. After heating over the substage lamp these
      elements also become less oil-miscible. The interfacial tension relations of
      blood cells, bacteria, and several cell products are tabulated.

PMID- 19869103
TI  - A STUDY OF HEMOLYTIC STREPTOCOCCI IN ACUTE RHEUMATIC FEVER, WITH AN ANALYSIS OF
      THE ANTIGENIC RELATIONSHIPS EXISTING AMONG CERTAIN STRAINS.
AB  - 1. Thirteen strains of hemolytic streptococci isolated from patients with acute
      rheumatic fever did not show any evidence of being related serologically. 2.
      Strains of hemolytic streptococci exist which, although identical by the
      agglutination test, do not show complete reciprocal agglutinin absorption. Sera
      prepared from such related strains may show some protective power in mice against
      another member of the group. 3. Some strains of hemolytic streptococci may absorb
      agglutinins from a serum prepared against another strain, and yet may fail to be
      agglutinated by that serum. 4. None of 20 strains of hemolytic streptococci
      isolated in New York City in 1924, and 1925, corresponded serologically with
      Dochez, Avery, and Lancefield's 4 type strains or with Gordon's Type I strain.

PMID- 19869104
TI  - THE PRODUCTION OF ALBUMINURIA BY RENAL VASOCONSTRICTION IN ANIMALS AND IN MAN.
AB  - EXPERIMENTS ARE DESCRIBED WHICH SHOW THAT: 1. Transient albuminuria follows the
      infusion of small doses of adrenalin into rabbits, if prolonged over several
      minutes. 2. Agents causing renal vasoconstriction also cause transient
      albuminuria in anesthetized, eviscerated dogs. 3. Cats eliminate albumin after
      having been frightened or enraged. 4. The drug ephedrine, which commonly causes
      renal vasoconstriction in animals, has been tested in man. Transient albuminuria.

PMID- 19869105
TI  - CONCERNING THE STABILITY OF THE ACID-BASE EQUILIBRIUM OF THE BLOOD IN PREGNANT
      ANIMALS.
AB  - 1. The acid-base equilibrium of the blood as indicated by determinations of the
      reserve alkali of the blood remains constant in non-pregnant animals at different
      age periods. This statement does not imply that the acid-base balance of such
      animals at different age periods is a stable balance. 2. In pregnant animals of
      the same age periods as the control animals there may develop an instability of
      this equilibrium which is either associated with the occurrence of a renal injury
      and which may be looked upon as a retention phenomenon, or arises independently
      of such an injury. In this latter group of animals the disturbance in the
      equilibrium increases in frequency and is earlier in its appearance in the
      gestation period as the age of the organism increases. 3. In old and in senile
      pregnant animals some physiological mechanism other than that of the kidney
      becomes unable to stabilize the acid-base equilibrium of the blood with the
      result that as the pregnancy advances this physiological state of the organism
      (gestation) becomes pathological.

PMID- 19869106
TI  - STUDIES ON X-RAY EFFECTS : XIV. THE EFFECT OF X-RAY ON THE DIVISION RATE OF
      PARAMECIUM.
AB  - Two races of paramecium were submitted for varying lengths of time to x-radiation
      and a large number of individuals were observed to determine the effect on the
      rate of division. The division rate of both races suffered a slight initial
      depression lasting for 2 to 5 days following the exposure. This depression is
      followed by complete recovery. Within rather wide limits the length of the
      exposure has, in these experiments, made no appreciable difference. Apparently
      the maximum effect of the x-rays is produced by relatively short exposures.
      Continued radiation produces little further change until exposures of 3 and 4
      hours are used, when precisely the opposite results are obtained from those
      obtained with shorter exposures. Doses repeated at various intervals have in
      general failed to interfere more markedly with the division rate than a single
      dose. Repeated radiation causes the cells to become slightly swollen without
      apparent interference with their viability.

PMID- 19869107
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : V. EFFECT OF ELECTROLYTES ON THE RATE
      OF INACTIVATION OF BACTERIOPHAGE BY ALCOHOL.
AB  - Addition of neutral salts to the lytic filtrate results in an increased rate of
      inactivation of the latter when alcohol is added to it. This effect of salts is
      the more marked the higher the valency of the cation. Conversely, removal by
      dialysis of salts originally present in the lytic filtrate tends to render lytic
      agent less sensitive to alcohol. Restitution of the original salt content to the
      dialyzed filtrate tends to bring the sensitiveness to alcohol in the dialyzed
      filtrate to the level of the non-dialyzed control. It appears, therefore, that
      inactivation of the lytic agent by alcohol depends directly on the rate of
      precipitation of the coagulable constituents of the medium, and is not the result
      of a direct toxic action of alcohol on "bacteriophagum intestinale." Considered
      in association with our earlier findings, these results speak in favor of the
      chemical nature of the agent of transmissible lysis.

PMID- 19869108
TI  - THE PRODUCTION OF PURPURA BY DERIVATIVES OF PNEUMOCOCCUS : I. GENERAL
      CONSIDERATIONS OF THE REACTION.
AB  - 1. Pneumococcus extracts have been shown to be capable of producing hemorrhagic
      purpura in white mice, rabbits, and guinea pigs. 2. The purpura-producing
      principle resists heating to 100 degrees C. for 10 minutes; it resists oxidation;
      it is filter-passing; its activity is destroyed by digestion with trypsin; it is
      obtained from pneumococcus extracts by full saturation with (NH(4))(2)SO(4),
      after the acetic acid-precipitable substances have been removed from the
      extracts. 3. The purpura-producing principle is common to all four types of
      pneumococcus and apparently bears no relation to virulence. 4. The purpura
      producing principle is probably a degradation product of pneumococcus. 5. This
      principle is not associated with the hemotoxin of pneumococcus, since the
      hemolytic activity of an extract may be destroyed without effect on the ability
      to cause purpura.

PMID- 19869109
TI  - A CHEMICAL STUDY OF THE SPECIFIC ELEMENTS OF TUBERCULIN : II. THE PREPARATION OF
      RESIDUE ANTIGEN FROM OLD TUBERCULIN.
AB  - A non-protein gum has been isolated from broth filtrates of human tubercle
      bacilli grown on a simple medium. It fixes complement and precipitates in high
      dilution in the presence of homologous immune serum, but fails to give a skin
      test in tuberculous animals. The preparation and some of the chemical properties
      of the substance are described.

PMID- 19869110
TI  - THE PRODUCTION OF PURPURA BY DERIVATIVES OF PNEUMOCOCCUS : II. THE EFFECT OF
      PNEUMOCOCCUS EXTRACT ON THE BLOOD PLATELETS AND CORPUSCLES.
AB  - A study has been made of the variation in number of the blood platelets, and the
      red and white blood cells of white mice injected with pneumococcus extract. The
      blood platelets were greatly diminished after the injection, the greatest
      decrease usually occurring after 24 hours. Purpuric lesions usually developed
      when the number of blood platelets became less than 500,000 per c.mm.
      Regeneration of the platelets was accomplished by the 4th to the 9th day but
      there was an overregeneration and the return to normal did not take place until 2
      weeks had elapsed. The red cells were also greatly reduced in number, but the
      rate of their destruction and regeneration was somewhat slower than that of the
      platelets. The leucocytes were slightly if at all influenced by the pneumococcus
      extract. Pneumococcus extracts were shown to be thrombolytic and hemolytic. Heat
      destroyed the activity of both the lysins in vitro. Heated extract produced
      purpura in mice but did not cause a severe anemia. Extracts adsorbed with either
      blood platelets or red blood cells showed a marked diminution in their
      thrombolytic and hemolytic activity in vitro. Such extracts, however, produced
      purpura as well as severe anemia and thrombopenia in mice.

PMID- 19869111
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : IX. THE RELATIONSHIP OF DOSAGE TO MORTALITY RATE, SURVIVAL TIME,
      AND CAGE POPULATION.
AB  - Epidemics of mouse typhoid set up among the Rockefeller Institute strain of mice
      were studied over a period of 6 months. During this time the relationship of cage
      number of mouse typhoid bacilli to mortality, total population, and survival time
      was determined. A single virulence titration of the epidemic strain was made, and
      at the end of the experiment all survivors were examined for evidence of
      infection. The following conclusions may be drawn for the data here presented. 1.
      The available dosage of mouse typhoid bacilli varied directly with the mortality
      (plus a time constant of 6 to 8 days) and inversely with the survival time. 2.
      The virulence of the epidemic strain appeared to be practically the same as that
      of the original stock culture. 3. About 53.5 per cent of the survivors of one
      epidemic and 68 per cent of those in the other showed, at the end of the
      experiment, no signs of infection; the others had either specific blood
      agglutinins, or living bacteria in their heart's blood, spleen, feces, or gall
      bladder. 4. During the course of the epidemic, the original infecting strain
      (mouse typhoid Type II-Bacillus pestis caviae) was almost entirely replaced by an
      antigenically dissimilar strain (mouse typhoid Type I-Bacillus enteritidis),
      probably introduced through the inadvertent inclusion of fecal carriers among the
      normal mice added as contacts.

PMID- 19869112
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : X. THE RELATIVE SUSCEPTIBILITY OF DIFFERENT STRAINS OF MICE TO
      PER OS INFECTION WITH THE TYPE II BACILLUS OF MOUSE TYPHOID (BACILLUS PESTIS
      CAVLAE). FURTHER STUDIES.
AB  - Four separate strains of mice have been tested for their relative susceptibility
      to per os infection with the Type II bacillus of mouse typhoid (Bacillus pestis
      caviae), 300 to 600 individuals of each strain having been employed in the course
      of 12 months. In confirmation of a previous paper, clear-cut differences in the
      susceptibility of these strains have been shown to exist. In general, the colored
      strains were distinctly less resistant than the albino strains.

PMID- 19869113
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : XI. SEASONAL VARIATION IN THE SUSCEPTIBILITY OF DIFFERENT STRAINS
      OF MICE TO PER OS INFECTION WITH THE TYPE II BACILLUS OF MOUSE TYPHOID (BACILLUS
      PESTIS CAVIAE). FURTHER STUDIES.
AB  - Four unrelated strains of mice were tested over a period of 1 year for their
      seasonal variation in susceptibility to per os feeding with a culture of Bacillus
      pestis caviae of known virulence. Certain consistent fluctuations, determined to
      be in general agreement with those already recorded in a previous paper, were
      found and described.

PMID- 19869114
TI  - THE RELATION OF THE THYROID GLAND TO THE SURFACE TENSION OF THE BLOOD PLASMA : I.
      THE EFFECT OF THYROIDECTOMY.
AB  - 1. Following thyroidectomy in guinea pigs, there is a gradual elevation of the
      surface tension of the blood plasma which reaches its height in from 19 to 22
      days after operation. This elevation is probably permanent, since we have found
      it to persist for as long as 120 days. 2. In our experiments, we found a few
      thyroidectomized animals in which the surface tension of the plasma was still
      within normal limits 24 and 120 days after operation. We suggest that these
      exceptions are due to three possible factors: (1) incomplete thyroidectomy; (2)
      presence of accessory thyroid tissue; (3) compensatory activity on the part of
      other organs. 3. The surface tension of the plasma from operated animals is
      higher than that from controls in both the initial and 20 minute determinations,
      but the difference is greater at the 20 minute period. 4. The time-drop
      (difference between the initial and 20 minute determinations) is somewhat greater
      in the plasma from normal than in that from operated animals. 5. It is suggested
      that these changes are due to a decrease in the amount of certain normally
      occurring surface-active substances, the production of which is directly or
      indirectly dependent upon the thyroid gland.

PMID- 19869115
TI  - THE RELATION OF THE THYROID GLAND TO THE SURFACE TENSION OF THE BLOOD PLASMA :
      II. THE EFFECT OF THE ADMINISTRATION OF THYROID EXTRACT AND THYROXIN.
AB  - 1. Determinations of the surface tension of blood plasma from guinea pigs, before
      and after feeding thyroxin, showed in most cases a definite decrease. Out of
      twenty-seven experimental animals, twenty showed a depression in the surface
      tension which ranged from 1.9 to 13.9 dynes, with an average of 5 dynes. Six
      animals showed variations hardly exceeding the limits of experimental error,
      while one showed an elevation of 1.1 dynes. 2. Six normal control animals, bled
      on the same days and kept under identical conditions, showed differences in the
      two determinations which ranged from a decrease of 0.5 to an increase of 0.6 of a
      dyne. One other control showed a drop of 1 dyne. 3. Two animals which had been
      fed large quantities of thyroid extract over a period of 10 days, gave values
      considerably below normal. One of these animals survived, and after 11 days
      during which no thyroid extract was given, the surface tension was found again to
      be within normal limits. 4. The hypothesis is advanced that these changes are due
      to an increase in the amount of certain normally occurring surface-active
      constituents, which are produced as a result of increased cellular metabolism.

PMID- 19869116
TI  - THE RELATION OF BACILLUS ABORTUS FROM BOVINE SOURCES TO MALTA FEVER.
AB  - 1. Comparative tests on guinea pigs with B. abortus yield the best results when
      minute doses are injected subcutaneously and the animal kept at least 4 weeks. 2.
      B. abortus gradually loses its virulence for guinea pigs under artificial
      cultivation. 3. Two cultures resembling B. abortus from cattle, isolated from
      human cases of so called Malta fever, are shown to be in their effect on guinea
      pigs not identical with the bovine strains. 4. The results of studies of B.
      abortus from swine indicate a close relation between the porcine strains and the
      two human strains.

PMID- 19869117
TI  - AGGLUTINATION AFFINITIES OF THE ABORTUS-MELITENSIS GROUP OF BACTERIA WITH SPECIAL
      REFERENCE TO TWO HUMAN STRAINS.
AB  - The conclusions to be drawn from this study are that while there appears to be
      evidence of serological distinctions between B. abortus and B. melitensis
      cultures as studied by earlier workers, the experiments reported in this paper
      show no serological distinctions among the six strains used in the study. B.
      melitensis II and B. melitensis III were found to be identical with the bovine
      and swine strains by means of agglutination and agglutinin absorption reactions
      in unheated sera, by agglutination in heated sera, and with the use of heated
      cultures in unheated and heated sera.

PMID- 19869118
TI  - THE ORIGIN OF THE LEPRA CELL.
AB  - 1. By means of the method of vital staining it is found that the lepra cell in
      rat leprosy is derived from the histiocyte. 2. From the similarity in morphology
      and function of the lepra cells in this condition and those of human leprosy, it
      seems likely that derivation of the cells in the two conditions is similar.

PMID- 19869119
TI  - EFFECTS OF SPONTANEOUS DISEASE ON ORGAN WEIGHTS OF RABBITS.
AB  - A group of 127 rabbits presenting clinical manifestations of disease of
      spontaneous origin was studied with a view to determining whether any relation
      could be detected between physical constitution as represented by organ weights
      and functional activity as measured by the efficiency of the reaction to disease.
      The results of the investigation are presented in tabular form and the values
      obtained are compared, by means of graphs, with corresponding values for normal
      rabbits. It was found that animals that were the subjects of disease showed
      decided changes in the weights of nearly all organs, changes which appeared to be
      of functional origin in that the values obtained for organ weights and
      coefficients of variation tended to conform, in general, with the efficiency of
      the reaction displayed by the various groups of animals into which the entire
      series was divided.

PMID- 19869120
TI  - ALLERGIC IRRITABILITY : III. THE INFLUENCE OF CHRONIC INFECTIONS AND OF TRYPAN
      BLUE ON THE FORMATION OF SPECIFIC ANTIBODIES.
AB  - 1. The allergic irritability of the guinea pig (capacity of the animal to react
      to antigenic substances) is increased by infection with Bacillus abortus and a
      streptococcus, by the dead tubercle bacillus, and by intensive treatment with
      trypan blue, respectively. The effect of these influences, while definite, is
      less pronounced than that previously found for infection with the tubercle
      bacillus. The production of anti-sheep hemolytic amboceptor was used as the test
      reaction in these cases. 2. The allergic irritability of the guinea pig with
      reference to anti-typhoid agglutinin is increased by infection with the tubercle
      bacillus. 3. The allergic irritability of the rabbit with reference to anti-sheep
      hemolytic amboceptor is increased by an infection of suitable severity with the
      tubercle bacillus. 4. In the guinea pig the curve of antibody production is
      complex. Its peculiarities are developed during the production of antityphoid
      agglutinins as well as that of anti-sheep hemolytic amboceptor. In the latter
      case injections of antigen subsequent to the first give rise to a curve of
      production unchanged in form but somewhat affected in the time relations. 5. The
      effects of infection with Bacillus tuberculosis on allergic irritability with
      reference to anti-sheep hemolytic amboceptor are operative throughout a course of
      immunizing treatments. The successive increases due to the cumulative effect of
      repeated doses of the antigen are developed on a higher level. The end-result is
      that the animal with increased irritability furnishes more antibody not only in
      response to the initial injection of antigen as previously described, but an
      absolute increase over the amount attainable by a comparable number of treatments
      in series. That portion of the final result contributed by the increase in
      allergic irritability appears to be no less, and may even in instances be
      somewhat more than that due to the earlier doses of the specific antigen.

PMID- 19869121
TI  - NUCLEAR INCLUSIONS IN THE TESTICLES OF MONKEYS INJECTED WITH THE TISSUE OF HUMAN
      VARICELLA LESIONS.
AB  - Eosin-staining nuclear inclusions resembling those deemed characteristic of a
      certain well known group of filterable viruses, amongst which is varicella, were
      found in vervets' testicles inoculated with emulsified tissue of human varicella
      lesions.

PMID- 19869122
TI  - THE TYPE OF PHAGOCYTIC CELL AND ITS RELATIVE PROPORTIONS IN HUMAN BONE MARROW AND
      SPLEEN, AS IDENTIFIED BY THE SUPRAVITAL TECHNIQUE, WITH SPECIAL REFERENCE TO
      PERNICIOUS ANEMIA.
AB  - In general, there is a reversal of the normal in the ratio of clasmatocytes in
      the spleen to clasmatocytes in the bone marrow in pernicious anemia, with a
      marked tendency toward the phagocytosis of young, immature, nucleated red blood
      cells in the bone marrow. The peripheral blood picture suggests that these cells
      had never been in circulation. The observations made do not indicate that the
      spleen takes any directly active part in an increased destruction of blood in
      pernicious anemia.

PMID- 19869123
TI  - EFFECT OF THYROIDECTOMY AND OF THYMECTOMY IN EXPERIMENTAL SYPHILIS OF THE RABBIT.
AB  - Experiments are described in which the thyroid or thymus gland of rabbits was
      removed prior to inoculation of the animals with Tr. pallidum. The effect of
      these procedures is described from the standpoint of the manifestations of the
      disease. After complete thyroidectomy, the disease was considerably more severe
      than in the controls and very markedly so in certain instances. Partial
      tyroidectomy, on the other hand, resulted in a milder disease than that of the
      controls. The effect of complete thymectomy was less pronounced than that of
      either complete or partial thyroidectomy, but, in general, the syphilis resembled
      that in partially thyroidectomized animals. These effects are discussed in
      relation to the host's reaction and resistance to experimental syphilis and the
      conclusion was reached that the integrity and balance of the glands of internal
      secretion play an important role in the mechanism of defense against this
      infection.

PMID- 19869124
TI  - VARIATIONS IN CO(2) REQUIREMENTS AMONG BOVINE STRAINS OF BACILLUS ABORTUS.
AB  - Strains of Bacillus abortus freshly isolated vary in their CO(2) requirements.
      The origin and sources of the strains growing with less dependence on CO(2) (or
      sealing) may be in vaccinal strains or possibly in continued existence in the
      udder. The importance of these possibilities makes it desirable that all strains
      isolated should be subjected to some such test as is outlined in these pages.

PMID- 19869125
TI  - FURTHER DATA ON THE EFFECT OF VACCINATION AGAINST BOVINE INFECTIOUS ABORTION.
AB  - The partial protection afforded by four injections of a heated culture of
      Bacillus abortus of normal virulence during the first pregnancy is in part lost
      in the second. The superiority of a single injection of a living culture of
      relatively low virulence is evident in both pregnancies. In the experiment
      described, the protection was complete.

PMID- 19869126
TI  - A RAPID METHOD FOR THE ISOLATION OF BACILLUS ABORTUS FROM UTERINE EXUDATE AND
      DISEASED PLACENTA.
AB  - A rapid method is described for the isolation of Bacillus abortus from the
      peritoneal cavity of the guinea pig following the injection of uterine exudate or
      placental tissue.

PMID- 19869127
TI  - STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY : III.
      SPONTANEOUS TUMORS OF THE LUNG IN MICE.
AB  - 1. The occurrence of tumors in the lung in mice is dependent to a certain extent
      upon the age of the individual. No tumors were found in the lungs of mice less
      than 8 months old. They occurred with greatest frequency in mice of about 24
      months or older. Mice may live to be more than 3 years old without developing
      growths in the lung. These facts show that the development of tumors of the lung,
      if hereditary, is a variable character. An individual, genetically a tumor mouse,
      may live to a great age without showing a tumor if the requisite environmental
      stimulus (external or internal) is lacking. Sex if effective at all has a
      comparatively slight influence upon the incidence of lung tumors. 2. Two strains
      of mice were studied which exhibit differences in their rates of incidence of
      lung tumors that are large enough to be significant. The conflict in the evidence
      from different laboratories as to whether or not tumors of the lung are the
      commonest type found in mice, is probably to be explained on the basis of a
      differing hereditary tendency to such growths in differing stocks. 3. Data from a
      number of sources indicate that offspring from parents free from lung tumors have
      a lower rate of lung tumor incidence than offspring from parents one of which had
      a tumor. If both parents had lung tumors the rate of tumor incidence among their
      offspring is increased still further. 4. In crosses between mice from strains
      which have high and low rates of incidence of lung tumor, tumors appeared in
      about half of the individuals of the first generation and in about one-quarter of
      the second generation. If the character responsible for the development of the
      growths is recessive it should not be found in the first filial generation unless
      both parents are carrying it. There is no proof that the female parents did not
      carry it but since they were taken from a strain in which the incidence of the
      growths was but 6.7 per cent the chances seem good that they were free from it.
      This suggests that the character determining the incidence of pulmonary tumors
      may be a dominant one. A dominant character is not expected to appear among the
      offspring from parents neither of which has shown the character. The numerous
      instances which have been tabulated in this paper of mice with lung tumors among
      the offspring of parents free from lung tumors, must be explained on the
      assumption that tumor susceptibility is not only dominant but variable and that
      some of the parents which did not actually develop tumors were genetically tumor
      mice and had the capacity for developing tumors although it was not brought out.
      As we have already concluded on the basis of the relationship between age and
      tumor incidence that susceptibility to the development of lung tumors is a
      variable character our explanation of the occurrence of tumor mice derived from
      tumor-free parents is justifiable. The existence of strains of mice with rates of
      incidence of lung tumors that differ as widely as do the two that we have
      studied, the relatively high incidence of pulmonary growths among mice of tumor
      parentage as compared with mice from non-tumor parents, and the fact that females
      from a strain in which pulmonary tumors are rare when crossed with individuals
      from a strain in which they are frequent give a fairly high rate of incidence of
      the growths among the first and second filial generations,-all these facts
      indicate that susceptibility to the development of tumors in the lung is an
      inherited character.

PMID- 19869128
TI  - EFFECTS OF INSULIN ON THE WEIGHT OF THE RABBIT'S SUPRARENAL GLANDS.
AB  - There is no gross hypertrophy of the adrenals in rabbits after long continued,
      daily doses of insulin.

PMID- 19869129
TI  - THE IMMUNITY PRODUCED BY THE GROWTH OF TETANUS BACILLI IN THE DIGESTIVE TRACT.
AB  - 1. A method for the production of tetanus by the injection of a fixed number of
      spores is described together with the tests made in selecting animals for
      experimental work. 2. Guinea pigs fed a single serological type of tetanus
      bacilli will, after 6 months, show considerable amounts of antitoxin in their
      sera and will manifest immunity to the type fed. To other types they are just as
      susceptible as are controls. 3. Animals fed several types are immunized to each
      of these types. It is pointed out in the discussion that the digestive tract of
      man may carry several types and that he probably reacts in a manner resembling
      the guinea pig carriers. 4. Guinea pigs that carry tetanus bacilli and have
      antitoxin in their sera show little if any resistance to tetanus toxin. 5. As
      there is no relation between the amount of antitoxin in the blood and immunity to
      tetanus we believe that other bodies, specific for type, must occur and make for
      the immunity observed.

PMID- 19869130
TI  - STUDIES ON THE BIOLOGY OF STREPTOCOCCUS : V. ANTIGENIC RELATIONSHIPS BETWEEN
      STRAINS OF STREPTOCOCCUS FROM SCARLET FEVER AND ERYSIPELAS.
AB  - 1. Strains of hemolytic streptococci isolated from cases of erysipelas
      agglutinate in a high percentage of instances with erysipelas immune sera. When
      agglutination occurs with one serum, the strain usually agglutinates with all
      other erysipelas sera. 2. Erysipelas immune sera agglutinate strains from
      erysipelas in a higher percentage of instances than they agglutinate scarlatinal
      strains. 3. Strains from miscellaneous pyogenic infections may agglutinate in
      these sera, but the percentage of positive reactions is low and a strain usually
      agglutinates in but one or two of several sera. 4. Erysipelas strains which
      agglutinate in immune sera are not necessarily identical, although identical
      strains may occur. Similarly, identical strains may occur among scarlatinal
      strains agglutinated by scarlatinal immune sera. 5. Erysipelas strains form a
      closely related group of hemolytic streptococci. Scarlatinal strains form an
      equally compact group. The two groups are related antigenically but less closely
      related than the strains within the groups. These groups are related to pyogenic
      strains, but less closely than they are related to each other. 6. Erysipelas,
      scarlatinal, or pyogenic strains which agglutinate in erysipelas or scarlatinal
      sera are capable of absorbing the agglutinin for all other strains except the
      homologous strain and strains identical with it. Strains identical with the
      homologous strain absorb the agglutinin completely. 7. Erysipelas or scarlatinal
      strains may absorb the common group agglutinin from their respective sera, when
      they are incapable of agglutination in these sera. 8. The agglutinogen is
      probably of complex or composite nature, with characteristic variations in the
      scarlet fever and erysipelas groups.

PMID- 19869131
TI  - COMPENSATORY HYPERTROPHY OF THE ADRENAL CORTEX.
AB  - 1. Removal of one adrenal in the albino rat is followed by hypertrophy of the
      remaining gland. In the case of female rats 90 days of age this compensatory
      hypertrophy amounted to 61 per cent. 2. The increase in size of the whole gland
      is due entirely to hypertrophy of the cortex. This increase in cortical tissue
      amounted to approximately 91 per cent and was due in large part if not entirely
      to an increase in the size of the cells. 3. No increase in the size of the
      medulla or its cells was found.

PMID- 19869132
TI  - STUDIES ON THE HISTOGENESIS OF AUTOPLASTIC THYMUS TRANSPLANTATIONS.
AB  - 1. The thymus gland of young rats autotransplants easily when inserted in the
      muscles of the abdominal wall. 2. Destructive changes take place during the first
      48 hours, when regenerative changes set in. 3. The regeneration is usually
      complete by the 14th day, when the new formed thymic lobules show differentiation
      into cortical and medullary zones. 4. The small thymic cells arise from the
      reticular epithelium in the regeneration of the transplant.

PMID- 19869133
TI  - STUDIES IN THE COMMON COLD : I. OBSERVATIONS OF THE NORMAL BACTERIAL FLORA OF
      NOSE AND THROAT WITH VARIATIONS OCCURRING DURING COLDS.
AB  - 1. The normal bacterial flora of the nose and throat of thirteen individuals has
      been studied over periods ranging from 5 to 9 months. 2. Observations have been
      made of qualitative and quantitative changes in the flora occurring in the course
      of colds and of throat infections appearing in the group. 3. The normal basic
      nasal flora includes Staphylococcus albus, diphtheroids, and for certain
      individuals Staphylococcus aureus and citreus. Occasional transient bacteria are
      Gram-negative cocci and non-hemolytic streptococci. 4. The normal basic throat
      flora includes Gram-negative cocci, non-hemolytic streptococci, and for certain
      individuals "large Gram-positive cocci," B. influenzae, Bacillus "X," and
      diphtheroids. Transient organisms are Staphylococcus albus, hemolytic
      streptococci,Staphylococcus aureus and citreus, and pneumococci. 5. No bacteria
      were found in early cold cultures to which a causative role could be assigned. 6.
      In the course of colds the basic flora of the nose was often scanty in the early
      stages. The throat showed reduction of prominence or alterations in predominance
      of the basic flora. 7. Certain organisms were prominent in colds, usually as late
      or secondary invaders, these included Staphylococcus aureus, hemolytic
      streptococci, and B. influenzae. 8. There was a striking increase in the
      incidence of hemolytic streptococci in throat infections.

PMID- 19869134
TI  - ON THE FREQUENCY OF SPONTANEOUS TUMORS IN THE DOMESTIC FOWL.
AB  - 1. Analysis of records from the Storrs Contest, the Harper Adams Trials, and a
      farm flock indicate an increase of tumors in the second half of the pullet year
      (May through October) over the first half (November through April). 2. Some
      evidence seems to indicate that heavy antecedent egg production is associated
      with a rise in tumor rate. 3. The normal annual tumor rate for fowls between the
      ages of 6 and 18 months is about 2 or 3 per cent. 4. The appearance of tumors in
      "epidemic" form probably indicates that the neoplasms found differ in etiology
      from those upon which the normal rate is based.

PMID- 19869135
TI  - THE EFFECT OF ANTISERUM AGAINST THE SOLUBLE TOXIC SUBSTANCE OF BACILLUS COLI IN
      BACILLUS COLI PERITONITIS.
AB  - When colon bacilli in sufficient numbers were injected into the peritoneal cavity
      of rabbits the animals died within a few hours. There was an incubation period of
      1 to 1(1/2) hours which was followed by a set of symptoms that culminated in
      death. The peritoneum, however, showed only very slight changes. It was thought
      that the soluble toxic substance of B. coli which was demonstrated by Aronovitch,
      Zinsser, and Branham may be an important lethal factor. Young cultures of B. coli
      in broth were centrifugalized and after killing the remaining bacteria by heat
      the supernatant fluid was injected into the peritoneal cavity of rabbits. There
      ensued the same set of symptoms terminating in death which were seen on the
      injection of the whole culture when the supernatant fluid alone was given. The
      potency of the toxic substance is variable. This variability is probably in part
      inherent in the material and in part depends upon the individual resistance of
      the animals. Rabbits were injected intravenously with the supernatant fluid of
      centrifugalized young cultures of B. coli and an antiserum was elaborated against
      the soluble toxic substance of this organism. When this antiserum was given
      intravenously to rabbits immediately or (1/2) hour after receiving
      intraperitoneally five times the usual lethal dose of B. coli, ten out of twelve
      animals survived.

PMID- 19869136
TI  - THE REACTION OF COW'S MILK TO BLOOD SERUM PRECIPITIN.
AB  - It seems well established that during normal lactation there passes a slight but
      well defined quantity of blood protein into the udder. When a specific serum
      precipitin is applied to diluted milk the reaction occurs at a relatively uniform
      level of dilution. This line may well be considered the normal level of blood
      protein elimination. In the main the serum protein level is the same when
      mastitis streptococci are present as when they are absent, provided they are not
      too numerous. On the other hand it has been shown that when streptococci are
      present in large numbers the milk while apparently normal reacts at dilutions
      considerably higher than the normal. In the non-lactating udder, particularly
      during the latter end of gestation, serum proteins accumulate. Little and Orcutt
      have shown that certain antibodies tend to become greatly concentrated within the
      udder. Howe and others have shown that the colostrum of cows is rich in blood
      proteins. It is to be noted, however, that colostrum while rich in serum proteins
      usually reacts with serum precipitin to about one-half the titer of the blood
      serum itself. It may well be that certain proteins of the blood passing into the
      acini are reabsorbed, leaving a portion of the antigen within the udder. Thus a
      gradual accumulation of antigen may occur. Shortly after parturition the udder
      may be drained with a consequent marked fall in serum content. There, however,
      apparently exists for the next few days considerable permeability of the
      capillaries for serum proteins. This is borne out by the reaction of the milk to
      the serum precipitin, since it may react above the normal level for as long as 10
      days or 2 weeks after parturition. During the course of inflammation there may
      occur a considerable outpouring of blood protein. In the severe cases the exudate
      may give a titer at as great a dilution as the blood serum. In other milder cases
      where the inflammation may be confined only to the mucosa of the milk cystern,
      there is usually little that is abnormal in the appearance of the milk. The
      precipitin test, however, indicates that serum proteins are present in definitely
      greater concentration than in normal milk. Of practical interest is the effect of
      heating the milk on the reaction of serum precipitin. Milk heated to a
      temperature as high as 66 degrees C. for 20 minutes will react at the same
      dilutions as the raw milk. Milk pasteurized at 68-69 degrees C. for 20 minutes
      will no longer react. The precipitin test, then, affords a ready means of
      detecting milk heated above 68-69 degrees C. It is assumed that the precipitin
      test may have some further practical application. The evidence presented
      indicates a well defined serum proportion in the milk which may be increased
      during inflammation of the udder. The experiments in which mastitis exudate was
      mixed with varying quantities of market milk indicate that such mixtures can
      readily be detected with serum precipitin. It seems not improbable that some such
      procedure might be applied as a presumptive test to the product of small herds or
      to the mixed milk of a number of cows.

PMID- 19869137
TI  - THE TRANSFORMATION OF MONOCYTES INTO FIBROBLASTS THROUGH THE ACTION OF ROUS
      VIRUS.
AB  - In normal cultures, the transformation of monocytes into fibroblasts generally
      occurred when cells became packed together through some mechanical factors that
      prevented their free migration and determined their accumulation. Various
      modifications of the medium, the addition of dead tissue, and of trypsin or the
      products of trypsin digestion, failed to bring about the transformation. The
      inoculation af cultures of monocytes with filtered extract of Rous sarcoma
      frequently determined the appearance of fibroblasts. The first change undergone
      by the monocytes cultivated in vitro was a large increase in their size. Later,
      the giant monocytes became transformed into cells that did not differ essentially
      from those that grow from a fragment of adult connective tissue.

PMID- 19869138
TI  - ANAPHYLACTIC SHOCK CAUSED BY ANTIBODY IN ANIMALS SENSITIZED BY ANTIGEN-REVERSED
      PASSIVE ANAPHYLAXIS.
AB  - Anaphylactic shock occurs (in rabbits) when the usual procedure for the
      production of passive anaphylaxis is reversed; that is, when an animal previously
      treated with antigen receives the corresponding antiserum by way of the
      circulating blood. This susceptibility to the action of anti-horse serum produced
      by injection of antigen reaches maximum intensity after an interval of 4 hours
      presumably required to permit penetration of the antigen in sufficient
      concentration into the tissues. Desensitization to the action of a shock
      producing dose of anti-horse serum can be brought about by repeated small doses
      of the same antiserum. Anaphylactic shock and local anaphylaxis manifested by the
      acute inflammation of an immunized animal when injected with the antigen used for
      immunization (Arthus phenomenon) occur under analogous conditions; that is, when
      antigen and antibody meet within the tissues. The peculiar characters of these
      reactions are dependent upon the site of entry of the irritating agent, which is
      the vascular system in one instance and tissue spaces in the other, and upon the
      concentration of antigen and antibody within susceptible tissues. Meeting of
      antigen and antibody within susceptible tissues is sufficient to explain the
      phenomena of local and general anaphylaxis so that it is unnecessary to assume
      the sudden formation of a toxic substance (anaphylatoxin).

PMID- 19869139
TI  - EFFECT OF JEJUNOSTOMY IN EXPERIMENTAL OBSTRUCTION OF THE JEJUNUM OF THE DOG.
AB  - 1. Jejunostomy does not prevent the development of the chemical changes of the
      blood characteristic of obstruction of the jejunum in the dog. 2. Jejunostomy
      following experimental obstruction of the jejunum has no beneficial effect upon
      the duration of life. There is some evidence that life may be shortened by early
      jejunostomy. 3. Treatment of jejunal obstruction with sodium chloride solution
      tends to prolong the life of animals regardless of jejunostomy.

PMID- 19869140
TI  - CALCIFICATION OF THE SUPRARENAL GLANDS OF CATS.
AB  - Calcification of the fascicular zone of the cortex has been observer in 64 of 257
      cats. It is always calcification and never ossification It is more common in
      young animals and in our experience is associated with distemper. In its severe
      forms it may be recognized clinically. The symptoms resemble those seen in cats
      surviving double suprarenalectomy for 2 to 3 weeks. The toxin producing the focal
      degeneration is dearly a very specific one since attempts to produce such lesions
      by several types of experimental injury have failed. The sequence of events
      appears to be similar to that present in other degenerative processes associated
      with calcification, namely cell injury and necrosis, deposition of calcium at
      first as fatty compounds which later change to carbonate and phosphate. It is
      suggested that this lesion should be considered in interpreting experiments in
      which cats are used.

PMID- 19869141
TI  - SYPHILITIC MYOCARDITIS IN THE RABBIT.
AB  - In the course of routine postmortem examinations of rabbits infected with
      Treponema pallidum, six cases of pronounced granulomatous myocarditis were
      encountered. Treponemata were not demonstrated in the lesions, but the clinical
      history, and the gross and microscopic appearance of the lesions seemed to
      warrant a diagnosis of syphilitic myocarditis. The lesions measured 1.0 cm. or
      more in diameter and histologically were practically identical with those
      described by Warthin in cases of syphilitic myocarditis in man. These are the
      first cases of syphilitic myocarditis or of visceral syphilis in the rabbit that
      have been reported.

PMID- 19869142
TI  - CULTIVATION OF RICKETTSIA-LIKE MICROORGANISMS FROM THE ROCKY MOUNTAIN SPOTTED
      FEVER TICK, DERMACENTOR ANDERSONI.
AB  - A systematic study of 74 ticks, the infectivity or non-infectivity of which was
      determined by biting experiments, inoculation of emulsions, and specific immunity
      tests, showed the presence in some instances of several types of microorganisms
      morphologically resembling the inciting microorganism of spotted fever. The most
      frequently isolated was B. rickettsiformis, n. sp., those less commonly
      encountered were B. pseudoxerosis, n. sp., and B. equidistans, n. sp. These
      organisms are non-pathogenic for the guinea pig, rabbit, and Macacus rhesus. In
      morphological features they resemble the forms found in smears and sections of
      the ticks, yet their presence had no relation to infectivity. Immunologically
      they are not related to the spotted fever virus. All three are pleomorphic under
      cultural conditions, and the question arises whether or not the minute non
      pathogenic Rickettsia forms and the somewhat coarser symbionts found in
      Dermacentor andersoni are morphological variations due to variations in
      nutrition, oxygen tension, tissue reactions, etc., in the different tissues and
      cells in which the organisms are embedded. At all events, the differentiation of
      the non-pathogenic Rickettsia-like organisms from Dermacentroxenus rickettsi is
      extremely difficult. In definitely infective ticks of the present study
      intranuclear forms were not constant. A point of special interest is that these
      non-pathogenic micro-organisms from ticks grow best at room temperature, in this
      respect resembling culturally certain flagellates inhabiting the alimentary tract
      of insects. The difficulty of obtaining initial growth on artificial media and
      the gradual adaptation to less specialized media are other notable
      characteristics of these organisms. The possibility that B. rickettsiformis is a
      non-pathogenic phase of the spotted fever organism, comparable with the avirulent
      flagellate culture forms of Leishmanias, seems remote in view of the negative
      immunological findings. Hereditary transmission of B. rickettsiformis is clearly
      indicated by its presence in large numbers in ovaries and egg cells, a
      characteristic also of the spotted fever organism and of other insect-borne
      Rickettsiae.

PMID- 19869143
TI  - EXPERIMENTAL BONE MARROW REACTIONS : I. ANEMIA PRODUCED BY COLLARGOL.
AB  - 1. The effect produced by the intravenous administration of collargol on the bone
      marrow of rabbits varies directly with the amount of collargol injected, and
      three fairly well defined stages could be recognized. (a) An initial stage after
      comparatively few and small doses, with erythrocytic and endothelial hyperplasia
      in the bone marrow and with evidences of this stimulation in the peripheral blood
      in the form of young erythrocytes and normoblasts. (b) An intermediary stage
      which followed the injection of larger amounts of collargol, and which was
      characterized by a predominant myeloid hyperplasia. (c) A final stage with marked
      bone marrow aplasia and with colloidal silver deposited in endothelial cells, as
      well as in clasmatocytes. This was associated with a high grade anemia with low
      color index, resembling aplastic anemia in its main features. This stage
      terminated fatally. 2. There was no evidence of injury to blood cells in the
      peripheral circulation. The erythrocytic bone marrow aplasia was present before
      any appreciable decrease of red blood cells was found in the peripheral blood. 3.
      The results were less clear-cut in a series of rats, but anemia of a similar type
      was produced in all animals when sufficiently large doses were injected. 4.
      Splenectomy did not alter the course in rats materially. 5. It is fair to
      conclude that the cause of the anemia produced may be sought in the deviation of
      the parental endothelial cell toward clasmatocyte formation at the expense of the
      development of erythrocytes. 6. It is suggested that the results may be offered
      in support of the theory of the endothelial origin of both clasmatocytes and red
      blood cells.

PMID- 19869144
TI  - EPIDEMIOLOGICAL STUDIES ON RESPIRATORY INFECTIONS OF THE RABBIT : VII. PNEUMONIAS
      ASSOCIATED WITH BACTERIUM LEPISEPTICUM.
AB  - 1. Four general types of spontaneous pneumonia, associated with strains of Bact.
      lepisepticum similar in biology and virulence, are described: (1) an acute,
      diffuse form, with subpleural and perivascular orientation of the exudate, (2)
      lobar, (3) pleuro-, and (4) abscess pneumonia. 2. The acute, diffuse, lobar, and
      pleuro pneumonias may be induced experimentally by intranasal instillation of a
      virulent strain of Bact. lepisepticum. 3. These same types occur when the
      organisms are inoculated intravenously, intratesticularly, and subcutaneously. 4.
      Intrabronchial insufflation of the organisms brings about infection in less than
      half of the animals. When effective, a sharply circumscribed, peribronchial
      lesion is found at the base of the lung, which spreads peripherally by direct
      extension, and generally by invasion of the blood stream. 5. It is concluded that
      differences in the types of pneumonia following infection with similar strains of
      Bact. lepisepticum depend upon the resistance of the animal, and that the usual
      portal of entry of this organism into the lungs, in cases of acute and lobar
      pneumonia, is by way of the blood stream.

PMID- 19869145
TI  - EPIDEMIOLOGICAL STUDIES ON RESPIRATORY INFECTIONS OF THE RABBIT : VIII. CARRIERS
      OF BACTERIUM LEPISEPTICUM.
AB  - Rabbits with no previous exposure to Bact. lepisepticum were given, intranasally,
      a known dose of one strain or another of this organism, or of B. bronchisepticus.
      The results give grounds for the following conclusions.

PMID- 19869146
TI  - ON THE DIALYSABILITY OF THE GROWTH-ACTIVATING PRINCIPLE CONTAINED IN EXTRACTS OF
      EMBRYONIC TISSUES.
AB  - These experiments appear to indicate that whatever substance in embryonic tissue
      extracts excites mitosis, and therefore would appear to be the growth-stimulating
      substance, is capable of passing through a collodion membrane which is
      impermeable to proteins, at all events in such concentration as would give rise
      to any biuret reaction. The substance is therefore diffusible.

PMID- 19869147
TI  - THE RELATION BETWEEN ATHEROSCLEROSIS AND INGESTED CHOLESTEROL IN THE RABBIT.
AB  - 1. The range of free cholesterol in the blood of rabbits, as determined by the
      Windaus method, varies from 35 to 125 mg. with a mean of 71 mg. per 100 cc. of
      blood. 2. The small amount of cholesterol contained in the high protein diet used
      by us in earlier work and causing atherosclerosis does not affect the blood
      cholesterol nor does it cause arterial disease. 3. In order to produce
      atherosclerosis it is necessary to feed at least ten times that amount of
      cholesterol. 4. In rabbits receiving such amounts both hypercholesterolemia and
      atherosclerosis occur, but it is not possible to establish any close parallelism
      between the two. High blood readings are found in rabbits with normal aortae and
      atherosclerotic rabbits in this series sometimes have shown a normal blood
      cholesterol. 5. With still greater doses of cholesterol one finally reaches an
      amount which regularly produces hypercholesterolemia and atherosclerosis within a
      few weeks. 6. A new series of rabbits fed the high protein diet shows that those
      rabbits which become atherosclerotic also develop hypercholesterolemia. We
      attribute this elevation of the blood cholesterol to a metabolic disturbance
      directly referable to the excess of protein in the diet and not to its
      cholesterol content.

PMID- 19869148
TI  - THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : I. THE ROLE OF THE
      RETICULO-ENDOTHELIAL SYSTEM IN THE PRODUCTION OF DIPHTHERIA ANTITOXIN.
AB  - 1. Following massive doses of India ink injected intravenously into guinea pigs
      before a subcutaneous injection of diphtheria toxin-antitoxin mixture, no
      antitoxin was found in the blood serum for 3 weeks, as indicated by
      intracutaneous tests, whereas an appreciable amount could be detected in non
      blocked, immunized control animals. 2. During the 4th week following
      immunization, the titer of the serum of blocked animals equaled that of non
      blocked controls within the limits of the intracutaneous test dose. 3. The
      smaller doses of India ink used in these experiments, given before immunization,
      had no stimulating effect on the production of diphtheria antitoxin but, on the
      contrary, also inhibited the appearance of this antibody, although to a less
      extent.

PMID- 19869149
TI  - STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION : V. THE RELATION OF VIRULENCE TO THE
      PNEUMOCOCCIDAL ACTIVITY OF NORMAL RABBIT SERUM-LEUCOCYTE MIXTURES.
AB  - Employing a method, described in an earlier publication, for testing the
      pneumococcidal activity of serum-leucocyte mixtures, a study has been made of the
      pneumococcus-destroying properties of the blood of a relatively susceptible
      animal, the rabbit, for pneumococci of low virulence for the species. It was
      found that rabbit serum-leucocyte mixtures possessed the power to kill avirulent
      pneumococci in relatively large numbers but failed to inhibit the growth of
      virulent organisms even in minute quantities. The results of numerous experiments
      in which all three types of pneumococci were employed indicated that the ability
      of a strain of pneumococcus to grow in rabbit blood is dependent on its virulence
      for the rabbit. The extreme susceptibility of the very young rabbit to strains of
      pneumococcus of low virulence for the full grown animal, was found to be
      associated with an absence of pneumococcidal properties in the blood of the young
      rabbit. These findings suggest that the relatively susceptible animals possess
      the same type of defense mechanism against pneumococcus infection as do the
      highly pneumococcus-resistant species.

PMID- 19869150
TI  - STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION : VI. THE SPECIFIC EFFECT OF
      PNEUMOCOCCUS SOLUBLE SUBSTANCE ON THE GROWTH OF PNEUMOCOCCI IN NORMAL SERUM
      LEUCOCYTE MIXTURES.
AB  - By means of a method previously described for demonstrating the growth-inhibitory
      and pneumococcidal power of normal serum-leucocyte mixtures, a study was made to
      determine the action of pneumococcus soluble substance on the growth of strains
      of pneumococci avirulent for rabbits and cats. It was found that the presence of
      a very small amount of the purified soluble substance of the homologous type
      markedly altered the conditions in the mixture so that even a small number of
      avirulent pneumococci were enabled to grow in the serum and leucocytes of animals
      which possess the power to destroy ordinarily such pneumococci in relatively
      large numbers. The action of the soluble substance was shown to be highly
      specific to type. A Type II substance assisted the growth of only Pneumococcus
      Type II, likewise a Type III substance, the growth of Pneumococcus Type III only.
      Experiments involving broth filtrates of young pneumococcus cultures in place of
      the purified soluble substances gave similar results, thereby establishing
      further the identity of the purified substance with the precipitable substance
      originally described in the filtrates of pneumococcus cultures. The effect of the
      soluble specific substance of pneumococcus in the serum-leucocyte mixtures is,
      therefore, to confer on the avirulent pneumococcus of the homologous type the
      growth capacity of a virulent organism. The mechanism of the reaction is briefly
      discussed.

PMID- 19869151
TI  - SOME CONDITIONS OF THE REPRODUCTION IN VITRO OF THE ROUS VIRUS.
AB  - A method has been developed by which the susceptibility of chickens to Rous virus
      can be tested, and the virulence of eight or ten different fluids compared in a
      single animal. The results of five series of experiments made with this technique
      can be summarized as follows: When a medium composed chiefly of chicken serum and
      Tyrode solution and containing no fresh tissues is inoculated with filtered
      extract of Rous and other sarcomas and incubated for 48 hours, it never produces
      a tumor after being injected into chickens. The virus has apparently been
      destroyed or at least has lost activity. But, in a solid medium, composed chiefly
      of serum and Tyrode solution and containing fragments of fresh tissues, the virus
      is found to increase readily, as shown in the first series of experiments. In the
      course of 15 months, the experiments have been repeated many times, with
      identical results. Flasks containing embryo pulp or leucocytes inoculated with
      filtered extract of sarcoma are used to keep on hand a constant supply of the
      Rous virus. The cultures of monocytes inoculated with the filtered extract often
      assume the appearance of the cultures of Rous sarcoma. They may also remain
      normal to all appearance despite the circumstance that the virus is multiplying
      within the medium. It is not certain that the activity of Rous virus is always
      accompanied by cell lesions, but there is no doubt that its increase depends on
      the presence of fresh tissues within the medium. The disappearance of the Rous
      virus from a medium that does not contain any fresh tissue may be interpreted as
      follows: the agent has been destroyed; or it is still present in a concentration
      lower than 1 in 50,000, which is the concentration required to produce a tumor
      even in the more susceptible chickens; or, according to the hypothesis of Gye, it
      is present in an inactive form. In the above experiments, the fresh tissues added
      to the medium might conceivably have enabled the virus to keep its full activity,
      through supplying the conditions requisite therefor, or they might merely have
      furnished an activating substance. The value of Gye's hypothesis was tested in a
      series of experiments. The results indicate that the tumor-producing virus
      present in the cultures was not composed of two parts, an inactive part
      multiplying in the medium, and an activating part supplied by the tissues. In
      another series of experiments, the relations between the reproduction of the
      virus and the quantity of the tissues contained in the medium were studied. The
      presence of a small fragment of leucocytic film or spleen tissue was sufficient
      to prevent the virus from disappearing. Approximately 1 c.mm. of spleen tissue in
      3,000 c.mm. of medium may on occasion maintain a concentration of Rous virus in
      this fluid sufficient to produce a tumor upon inoculation into chickens. But this
      rarely happens. Generally when the medium contained only one fragment of spleen
      or leucocytic film, or 1 drop of embryonic pulp, the virus disappeared rapidly.
      When the quantity of tissue was from five to nine times larger, an abundant
      production of virus was practically always found. It became obvious that the
      quantity of active virus present in a medium containing multiplying cells depends
      upon the amount of tissue in the medium. In the fourth series of experiments, the
      kind of cells needed for the multiplication of the virus was ascertained. Rous
      virus was found to disappear rapidly from the fluid of cultures of fibroblasts,
      while it multiplied readily in cultures of leucocytes, the total volume of both
      tissues being approximately the same. It should be remembered that strains of
      fibroblasts obtained from Rous and other sarcomas very rarely produce tumors upon
      inoculation into chickens, while the inoculation of cultures of macrophages from
      the same tumors practically always determines their appearance. The fifth series
      of experiments showed that the cell metabolism is an important factor in the
      reproduction of the virus. When the activity of tissues had been suppressed or
      very much decreased by freezing, no virus was produced, while it multiplied
      readily in the control. The lack of oxygen for a period of 24 or 48 hours stopped
      cell proliferation, and at the same time the production of Rous virus ceased.
      However, the fluid of some of these dead or inactive cultures, after 6 days
      incubation, was still able to give rise to a small tumor upon inoculation into a
      chicken. There is an evident relation between the proliferating activity of the
      tissues and the production of the virus. But the agent may persist for several
      days in association with dead tissues. It may be concluded that the reproduction
      in vitro of the active virus depends on the presence of fresh tissues in the
      culture and upon the quantity, the activity, and the nature of the cells
      contained in the medium.

PMID- 19869152
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : V. (a) INFLUENCE OF LYMPH
      SOLUBLE TISSUE MATERIALS ON THE SIGNIFICANCE OF THE COLORATION WITH SOME
      PHTHALEIN INDICATORS.
AB  - The present paper is the first of two dealing with experiments which were planned
      to disclose the meaning of the colors assumed by mammalian tissues when vitally
      stained with some phthalein indicators. Derivatives of the tissues themselves
      were employed after tests had shown, in agreement with certain facts in the
      literature, that inferences from model experiments, so called, would be
      misleading. Organs were perfused with water, or salt, or lymph of the same
      creature and extracted with small quantities of the fluid. The turbid extracts
      were colored with phthalein, the reaction determined colorimetrically with the
      aid of an arc light, and the findings were compared with potentiometer readings
      upon the material. The results of the two methods were in close agreement. The
      significance of the data will be discussed in our second paper.

PMID- 19869153
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : V. (b) INFLUENCE OF LYMPH
      INSOLUBLE TISSUE MATERIALS ON THE SIGNIFICANCE OF THE COLORATION WITH SOME
      PHTHALEIN INDICATORS.
AB  - The influence of lymph-insoluble tissue materials upon the colors manifested by
      phthalein indicators has been tested by comparing the hue of sections of various
      organs, stained by immersion in colored lymph, with the hue of the surrounding
      fluid. The reaction has been brought to approximate that of life by a greater or
      less saturation of the material with carbon dioxide. No evidence has been
      obtained of indicator errors referable to the association of the phthaleins with
      tissue substances. The inferences to be derived from the experiments, and from
      others detailed in a preceding paper, are discussed. The results of them all are
      in essential agreement. They demonstrate that the observed hues in tissues
      vitally stained with phenol red, brom cresol purple, and chlor phenol red cannot
      be laid to indicator errors resulting from an association of the phthalein with
      tissue materials. The fact is of special note in connection with organs which
      exhibit, when stained, the colors indicative of an outspoken acidity. The
      findings constitute a control upon the influence of the tissue materials on the
      colors manifested by the phthalein indicators when used as vital stains; but they
      leave untouched the problem of the influence of tissue activities upon the
      coloration.

PMID- 19869154
TI  - STUDIES OF HYPERTHYROIDISM : III. BILE PIGMENT PRODUCTION AND ERYTHROCYTE
      DESTRUCTION IN THYROID-TREATED AMPHIBIAN LARVAE.
AB  - Experimental hyperthyroidism in urodele larvae (Amblystoma) and anuran larvae
      (Rana, Bufo, and Hyla) is accompanied by definite changes in bile color. The
      normal pale green, or pale yellow-green, color of the full gall bladder changes
      progressively after thyroid administration to a brighter green, then emerald
      green, and finally a very dark green. In several hundred observations no
      exceptions were noted. The bile pigment, biliverdin (and its derivatives), is
      elaborated from the hemoglobin of worn out erythrocytes. Thyroid administration
      induces an increased rate of erythrocyte destruction, and this is followed by an
      increased output of bile pigment. Other minor factors are mentioned which may to
      a limited extent modify the color of the bile. Erythrocyte destruction occurs
      largely by enucleation, cytoplasmic segmentation, and fragmentation, and is
      probably widespread in the body. Many fragments and senile red cells collect in
      the liver. During the later stages of thyroid treatment the macrophages become
      conspicuously active. They are especially abundant in the liver, the gut, and the
      gills. In addition to the hemoglobin eliminated after transformation into bile
      pigment, some is transported by macrophages through the gut lining, and to a less
      extent through the involuting gill epithelium, and thus eliminated from the body.

PMID- 19869155
TI  - CHANGES IN THE REACTION POTENTIAL OF A TRANSPLANTABLE TUMOR.
AB  - A transplantable tumor, known as dBrD, gave very uniform results in a series of
      mice of known pedigree for a period of about a year. See PDF for Structure We may
      say that the reaction potential existing between the tumor and individuals
      inoculated was the same during this first part of the experiment. This tumor will
      grow in a mouse progressively provided there be present simultaneously at least
      from six to eight independently segregating genetic factors (genes) in the
      fundamental make-up of the host derived from the zygote that gave rise to the
      individual. In the course of routine transplantation of this tumor, there was a
      sudden change in this hitherto constant reaction potential resulting in at least
      three types of transplantable tumors-new types as far as their physiological
      activity and reaction potential are concerned. From a single original
      transplantable mass, I have therefore obtained four masses that remain true to
      type at least for some months of continued experimentation. These four types are
      (1) the original tumor, dBrD, still giving a six to eight Mendelian factor ratio,
      (2) dBrDm giving a two factor ratio, (3) dBrDBl showing another two factor ratio,
      and (4) dBrDBs giving a one factor ratio. The number of factors involved in the
      transplantability for the several tumors investigated are given in Table III.

PMID- 19869156
TI  - THE GEOGRAPHICAL DISTRIBUTION OF SPONTANEOUS ENCEPHALITIS IN RABBITS.
AB  - The observations reported in this paper seem to justify the hope that the
      obstacle afforded to experimentation by the frequent presence of spontaneous
      encephalitis and nephritis in American and European rabbits does not exist to the
      same degree in rabbits from certain other localities. The observations are,
      furthermore despite their obvious limitations, in conformity with the theory that
      the disease is not one common to domestic rabbits everywhere, but rather that it
      occurs in special localities from which, given favorable conditions, it may
      spread. Thus far it has not been reported in tropical climates or south of the
      equator.

PMID- 19869157
TI  - ORGAN WEIGHTS OF NORMAL RABBITS : SECOND PAPER.
AB  - The results of a second series of organ weight determinations on normal rabbits
      are reported and the values obtained are compared with those for the first
      series. Figures are also given which represent the results obtained by combining
      the two series of animals or from weight determinations made on 645 apparently
      normal rabbits selected from stocks used for various experimental purposes.

PMID- 19869158
TI  - STUDIES ON REGENERATION OF BACTERIOPHAGE : II. THE INFLUENCE OF OXYGEN UPON THE
      BEHAVIOR OF BACILLUS COLI TOWARDS LYTIC PRINCIPLE.
AB  - The investigations of the influence of oxygen on the bacteriophage phenomenon
      recorded in this paper show that this factor plays an important role which is due
      exclusively to its ability to induce certain changes in the behavior of bacterial
      cells towards lytic principle. At certain H ion concentrations both aerobic and
      anaerobic cultures can be made resistant in the absence of lytic principle. The
      resistance thus acquired is of a stable nature under suitable conditions. If the
      lytic principle is added to aerobic or anaerobic types of resistant strains the
      cultures are able to regenerate it to a certain extent. However they do not
      undergo any visible lysis themselves even under the action of lytic principles
      which were passed through several generations of these types. The principles
      regenerated by both types of resistant cultures are identical in action with each
      other as well as with the stock lytic principle. These experiments suggest a new
      method of investigation into the hitherto unexplained nature of resistance of
      bacteria towards bacteriophage.

PMID- 19869159
TI  - STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY : VI. THE RELATION OF BILIARY
      INFECTIONS TO THE GENESIS AND EXCRETION OF UROBILIN.
AB  - Experimental infection of the intubated and previously sterile biliary tract of
      the dog with particles of the stools leads to a formation of urobilin from the
      bilirubin of the bile as it flows through the ducts. No urobilinuria occurs,
      however, unless temporary biliary obstruction is produced, or the liver
      parenchyma injured. Then urobilinuria develops, despite the fact that no bile is
      reaching the intestine and, by corollary, no urobilin being formed there.
      Cholangitic urobilinuria, as one may term the phenomenon just described, to
      distinguish it from the urobilinuria having origin in pigment absorbed from
      within the intestine, is far more pronounced in animals possessing a healthy gall
      bladder than in those with a pathological gall bladder or with one prevented from
      functioning by severance of the cystic duct. These facts suggest that there may
      be an active absorption of urobilin from the normal gall bladder. There can be no
      doubt that the pigment is absorbed from within the bile ducts. There is no
      evidence whatever to justify the belief that urobilin is ever formed through the
      action of liver parenchyma. There may conceivably be an intralobular formation of
      the pigment consequent upon the activity of bacteria within the liver tissue,
      though such a happening has yet to be demonstrated.

PMID- 19869160
TI  - STUDIES ON THE EFFECT OF CERTAIN TOXIC SUBSTANCES IN BACTERIAL CULTURES ON THE
      MOVEMENT OF THE INTESTINES : I. THE EFFECT OF SOLUBLE TOXIC SUBSTANCES OF YOUNG
      CULTURES OF BACILLUS PARATYPHOSUS B.
AB  - Following intravenous injection, filtrates of young cultures of B. paratyphosus B
      often produce marked diarrhea in rabbits. A study was made of the effect of these
      toxic filtrates on the motility of the small intestines of the rabbit. The
      observations were made on a segment of the small intestines in situ, and in the
      living animal. It was found that an immediate slight rise of tone of the
      longitudinal muscles occurred following intravenous injection of sterile broth.
      The same rise was noted after the injection of the toxic filtrate; but with these
      it was followed later (10 minutes elapsing at least) by a very strong but gradual
      rise of the diastolic and systolic tone, i.e., by spasmodic contraction of the
      intestinal muscle, which persisted at times for as long as 2 hours. In order to
      record simultaneously the effect on the longitudinal and circular muscles, and
      the propulsive efficiency of the segment the Sollmann and Rademaekers
      modification of Baur's technique was employed. This arrangement showed that the
      stimulation of the longitudinal muscles is accompanied by a similarly strong
      stimulation of the circular muscles, by peristalsis, and therefore by a greatly
      increased propulsion of intestinal contents which was sufficient to overcome the
      inhibition that usually occurs after preparation of the animal. With this
      arrangement an instance of peristaltic spasm was also noted. Broth alone failed
      to produce the phenomenon. Isotonic magnesium chloride or sulfate added to the
      bath relaxed the muscles again. Animals under deep urethane anesthesia did not
      show the diarrhea occurring in the intact controls, but sometimes exhibited it
      after the effect of the anesthetic had disappeared. So far no effects have been
      observed on the isolated strip (Magnus method), and further studies are being
      made to localize the effect, to neutralize it with a specific antiserum, and to
      observe the effect of filtrates of other members of the bacterial group including
      the dysentery bacilli.

PMID- 19869161
TI  - THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : II. THE COMPLEMENT
      TITER AFTER BLOCKADE AND THE PHYSIOLOGICAL REGENERATION OF THE RETICULO
      ENDOTHELIAL SYSTEM AS MEASURED BY REDUCTION TESTS.
AB  - 1. Intravenous injections of India ink into guinea pigs caused a decided drop in
      the complement titer which set in as early as 15 minutes after the injection, but
      did not reach its maximum for 3 hours. This drop was followed by a return to
      normal within the first 24 hours following the injection. 2. India ink mixed in
      vitro with guinea pig serum adsorbs the complement almost immediately to its full
      extent. 3. By means of reduction tests (methylene blue and nitroanthraquinone) it
      was shown that the respiration of the cells of the liver and spleen of guinea
      pigs was markedly impaired for the first 8 hours, following an intravenous
      injection of ink. Evidences of a return to normal functional vitality, however,
      became apparent by the end of the 1st day after the injection.

PMID- 19869162
TI  - MELANOMA (SARCOMA) OF THE EYE IN A SYPHILITIC RABBIT.
AB  - A melanotic tumor developed in a defective eye of a syphilitic rabbit following
      repeated genital inoculations with Treponema pallidum. The appearance of the
      tumor coincided with the development of a syphilitic lesion in the same eye,
      suggesting a relation between the occurrence of the two lesions.

PMID- 19869163
TI  - THE CULTIVATION OF THE GRANULES OF VACCINIA VIRUS.
AB  - The technique is described whereby vaccinia "granules" are separated from all
      other material of glycerolated vaccinia calf lymph and cultivated in vitro with
      embryonic tissues. These "granules"remain alive, as tested by rabbit corneal
      inoculation, for as long as 71 days, when grown in connection with growing
      tissue; they fail to remain potent if cultivated with dying cells, showing in
      this way the same characteristics as whole vaccine virus. The potency of the "
      granules" increases with the age of the culture under the first mentioned
      conditions. The fluid part of the vaccinia lymph which remains after the removal
      of all "granules," is impotent under all conditions.

PMID- 19869164
TI  - THE PRESENCE OF DESQUAMATED ENDOTHELIAL CELLS, THE SO CALLED CLASMATOCYTES, IN
      NORMAL MAMMALIAN BLOOD.
AB  - 1. There is a practically constant desquamation of endothelial cells into the
      circulating blood in rabbits and man. 2. These endothelial cells represent the
      entire range in size of endothelium from very small cells, possibly from
      capillaries, up to the type of the large Kupffer cell. 3. These desquamated cells
      can be discriminated from monocytes. 4. There are common morphological and
      functional characteristics among the following cells: the clasmatocytes from the
      specific endothelia, such as the cells from the sinuses of the liver, spleen, and
      bone marrow; the clasmatocytes of the diffuse connective tissues; and desquamated
      endothelial cells occurring in normal and pathological blood. 5. There are four
      strains of white cells in the normal circulating human and rabbit blood,
      granulocytes, lymphocytes, monocytes, and endothelial phagocytes.

PMID- 19869165
TI  - NORMAL AND PATHOLOGICAL FRAGMENTATION OF RED BLOOD CELLS; THE PHAGOCYTOSIS OF
      THESE FRAGMENTS BY DESQUAMATED ENDOTHELIAL CELLS OF THE BLOOD STREAM; THE
      CORRELATION OF THE PEROXIDASE REACTION WITH PHAGOCYTOSIS IN MONONUCLEAR CELLS.
AB  - 1. There is constantly some breaking down of red cells in the circulation by
      fragmentation. 2. The fragments of red cells, as well as whole red cells, are
      phagocytized and destroyed by clasmatocytes or endothelial phagocytes. 3. When
      there is an increase in fragmentation in abnormal or pathological states,
      desquamated endothelial cells of the blood stream, as well as the clasmatocytes
      of the tissues, increase proportionately and take in these fragments. These cells
      are to be distinguished from eosinophilic leucocytes by the nature of their
      granules, by the type of motility of the cells, and by a negative peroxidase
      test. 4. The desquamated endothelial cells, clasmatocytes, in the circulating
      blood are positive to the peroxidase test only when they have taken in positive
      material. 5. The monocytes show marked variations of the oxidase reaction in
      different species and to different techniques. With the Sato and Sekiya technique
      most monocytes of human blood are positive, while most of them in rabbit blood
      are negative, but both positive and negative reactions are found in both human
      and rabbit blood.

PMID- 19869166
TI  - ETIOLOGY OF OROYA FEVER : I. CULTIVATION OF BARTONELLA BACILLIFORMIS.
AB  - A pure culture of a microorganism resembling in morphology and pathogenic action
      Bartonella bacilliformis has been obtained from blood taken during life from a
      case of Oroya fever which ended fatally. The blood taken at Lima into citrate
      solution and transported to New York at refrigerator temperature yielded positive
      cultures 28 days after its withdrawal from the patient. The strain of Bartonella
      bacilliformis thus isolated grows well on the semisolid leptospira medium, and
      also on slant agar containing animal blood. The initial growth is not readily
      recognizable to the naked eye, but the presence of the organisms can be
      determined by means of the dark-field microscope and by Giemsa and Gram staining
      methods. No growth has been obtained on the more ordinary culture media. The
      organism is an obligate aerobe, is Gram-negative, and under certain cultural
      conditions motile. All the forms which have been described as occurring in human
      red corpuscles may be found in the cultures, and in addition many granular and
      coarsely irregular forms have been met with. The inoculation of cultures of
      Bartonella bacilliformis into Macacus rhesus produces infection and gives rise to
      effects which differ with the mode of inoculation. The intravenous injection of
      the culture into young macaques induces a prolonged irregularly remittent fever.
      The organism can be cultivated from the blood over a long period, and it has been
      detected within the red corpuscles of the monkeys, reproducing the precise
      appearances observed in human cases of Oroya fever. The intradermal injection of
      the culture into the eyebrow of young macaques gives rise to nodular formations
      rich in new blood vessels and showing the bacilliform organism within the
      endothelial cells. From the experimentally induced nodules cultures of the
      organism are readily recovered.

PMID- 19869167
TI  - A FILTER-PASSING VIRUS OBTAINED FROM DERMACENTOR ANDERSONI.
AB  - An invisible, filter-passing virus, pathogenic for the guinea pig, and capable of
      cultivation on special media for at least seven generations, has been isolated
      from a tick of the species Dermacentor andersoni. One of two monkeys (Macacus
      rhesus) inoculated became infected, and in one rabbit the result was negative.
      The virus has been transmitted from infected guinea pigs to ticks as also in one
      instance by tick feeding from an infected tick to a guinea pig The presence of
      the virus in the tick is more easily demonstrated by the inoculation of guinea
      pigs with a suspension of the tick viscera. Continuous high fever (104.5-106.5
      degrees F.) and enlargement of the spleen are the chief symptoms of the infection
      in guinea pigs. After the febrile attack the guinea pigs are not susceptible to
      reinoculation with the cultured virus but are subject to infection with the virus
      of spotted fever, and vice versa.

PMID- 19869168
TI  - THE ORGANISM ASSOCIATED WITH SPECIFIC INFECTIOUS CYSTITIS AND PYELONEPHRITIS OF
      COWS.
AB  - A Gram-positive diphtheroid isolated from spontaneous cases of cystitis and
      pyelonephritis of cows on five farms has been studied. All the strains obtained
      were of the same general morphology. They possess similar cultural
      characteristics and to a great degree similar agglutination affinities. The
      organism is not pathogenic for the ordinary laboratory animals. It produces no
      toxin. Cows injected intravenously with broth cultures failed to develop the
      disease. On the other hand, small quantities of cultures introduced into the
      bladder by way of the urethra gave rise to a typical persistent cystitis. There
      is evidence for a transmission of the disease by contact infection, as when the
      same individual curries both normal and infected cows.

PMID- 19869169
TI  - A BIOLOGICAL CLASSIFICATION OF ENCAPSULATUS PNEUMONIAE (FRIEDLANDER'S BACILLUS).
AB  - A biological classification has been made of thirty strains of Friedlander's
      bacillus. This study reveals that there exist among these strains three sharply
      defined and specific types and one heterogeneous group. The three types are Type
      A, fifteen strains; Type B, six strains; Type C, three strains; and Group X, six
      strains. The agglutination, agglutinin adsorption, protection, thread, and
      precipitin reactions have been employed in the working out of this
      classification, and the types have been proved highly specific by means of each
      serological test.

PMID- 19869170
TI  - THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : III. THE PRODUCTION OF
      ACTIVE AND PASSIVE ANAPHYLAXIS IN THE BLOCKED ANIMAL.
AB  - 1. Guinea pigs injected intravenously with massive doses of India ink before
      active sensitization exhibited occasionally a more or less marked, decreased
      sensitiveness to the reinjection of the antigen. 2. The serum of rabbits which
      had received massive doses of India ink before the sensitizing injections, showed
      approximately the same titer of anaphylactic antibodies as that of sensitized
      normal control animals, as demonstrated by the degree of passive sensitization
      induced in guinea pigs. 3. The precipitin titer of sensitized rabbits blocked
      with massive doses of India ink was somewhat lower than that of sensitized normal
      controls. In one instance, the intravenous injection of smaller doses of India
      ink was followed by a higher precipitin titer. No uniform relation was found
      between the height of the precipitin titer and the anaphylactic power of the
      antiserums. 4. One blocking injection of India ink given to guinea pigs before
      passive sensitization did not interfere with the occurrence of anaphylactic shock
      nor alter its nature.

PMID- 19869171
TI  - IMMUNOLOGICAL STUDIES WITH HERPES VIRUS WITH A CONSIDERATION OF THE HERPES
      ENCEPHALITIS PROBLEM.
AB  - In the preceding experiments observations have been reported upon the nature of
      herpes virus which confirm the suspicion that the virus is intracellularly
      located in the infected nervous system. In regard to the immunological conditions
      existing in this disease, our experiments have reaffirmed that herpes virus can
      be neutralized with the serum of actively immunized animals and have offered an
      explanation for the irregularity of the results of others, as well as our own. It
      has been found that brain extracts possess some virus-neutralizing power, but
      considerably less than the serum of the corresponding animals. Attempts at
      passive immunization with neutralizing serum were uniformly negative, even when
      the serum was introduced into the cisterna magna 12 to 24 hours before infection
      with the virus. It has been shown that active immunity can be attained only when
      some degree of reaction to the living virus has occurred. Rabbits which survived
      neutralized serum-virus mixtures did not acquire immunity nor did those treated
      with virus phenolized to the extent of actual destruction. This point suggests a
      reinvestigation of the Semple method of rabies immunization. In so far as our
      studies touched upon the herpes-encephalitis problem we have uniformly failed in
      attempts to transfer herpes virus directly from man to rabbits. These results are
      in contradiction to those of most of the earlier workers, but in keeping with the
      recent reports of Flexner and Amoss. Attempts to overcome the difficulty of
      transfer by the recently published technique of Perdrau were unsuccessful.
      Furthermore, animals repeatedly treated with human encephalitis material, either
      fresh or glycerolated, as practised in the Perdrau method, failed to acquire the
      slightest degree of immunity to subsequent herpes inoculation. By the inoculation
      of very small doses or by infection of partially immunized rabbits, as described
      above, we have succeeded in modifying the characteristic herpetic syndrome in
      rabbits in a manner which simulates many of the clinical features of human
      encephalitis. Our own experience forces the conclusion that no valid proof exists
      upon which can be based an assertion concerning the identity of the virus of
      herpes with that of encephalitis lethargica. Either the two viruses are entirely
      unrelated, or else prolonged sojourn in the central nervous system of man
      attenuates the virus for rabbits to an extent analogous to that in which rabies
      virus is attenuated for man by passage through rabbits. The isolated successes of
      Levaditi and of Doerr and their assistants might thus be regarded as fortunate
      exceptions in which material incompletely attenuated had been at their disposal.
      We suggest this point of view as an alternative working hypothesis largely
      because the results we are reporting, as well as those of Flexner and Amoss, are
      in flat contradiction to the reported successes of earlier workers and the more
      recent experiments of Perdrau. The experiments of the latter, as described,
      cannot be explained by the occasional existence of spontaneous encephalitis in
      his rabbits, nor by the assumption that a herpes virus fortuitously coexisted
      with that of lethargic encephalitis in his material, inasmuch as this material
      alone at first injection or in the unglycerolated state failed to infect. It is
      also possible to conceive that human beings may, by repeated skin infections,
      attain a not inconsiderable partial immunity to herpes virus, which would explain
      the nature of the clinical course (as in our partial immunity rabbits) as well as
      the innocuousness of direct injections of herpetic virus into man, as reported by
      Bastai and Busacca, and the finding of herpes virus in human beings not suffering
      from lethargic encephalitis. These suggestions are discussed in order to give
      this important problem the broadest possible consideration. For the time being,
      however, such reasoning cannot be taken as more than a logical possibility
      impressed upon us by our partial immunization experiments. All other experimental
      evidence obtained by direct inoculations with the limited material at our
      disposal tends to render identity of the two varieties of viruses unlikely.

PMID- 19869172
TI  - THE SKIN RESPONSE OF RABBITS TO NON-HEMOLYTIC STREPTOCOCCI : I. DESCRIPTION OF A
      SECONDARY REACTION OCCURRING LOCALLY AFTER INTRADERMAL INOCULATION.
AB  - 1. Rabbits inoculated intradermally with certain strains of green streptococci
      have well marked lesions which, after reaching a maximum size in 24 to 48 hours
      and then beginning to retrogress, show in over 50 per cent of the animals a
      secondary increase in size and other signs of inflammation about 8 or 9 days
      after inoculation. 2. This secondary reaction may follow the inoculation of a
      variety of strains of green-producing streptococci from various sources, of
      indifferent streptococci, and occasionally of pneumococci. 3. The inoculation of
      hemolytic streptococci, staphylococci, Micrococcus catarrhalis, or Bacillus coli
      has not been followed by this secondary reaction. 4. The secondary reaction is
      not due to increased activity of the injected bacteria since the lesions are
      usually sterile at the time it occurs and since the secondary reaction occurs
      after inoculation of killed organisms as well as after that of living ones. 5. A
      second inoculation of green streptococci into a rabbit within 9 weeks of a first
      injection is followed by a primary but not by a secondary reaction. This
      inhibition of the secondary reaction is not specific; for the phenomenon of
      secondary reaction can be completely inhibited by previous inoculations of the
      rabbit with any living streptococcus and usually with pneumococci. Killed
      organisms are less effectual. 6. Preliminary injection with staphylococci,
      Micrococcus catarrhalis, and Bacillus coli has not prevented the appearance of a
      secondary reaction in response to subsequent injections of green streptococci. 7.
      The agent responsible for the secondary reaction has not as yet been determined;
      its nature is discussed. The phenomenon is possibly a form of allergic reaction.

PMID- 19869173
TI  - THE SKIN RESPONSE OF RABBITS TO NON-HEMOLYTIC STREPTOCOCCI : II. ATTEMPTS TO
      DETERMINE WHETHER THE SECONDARY REACTION IS OF THE NATURE OF AN ARTHUS
      PHENOMENON.
AB  - An attempt has been made to interpret on the lines of the Arthus phenomenon the
      secondary reaction which follows the intradermal inoculation of certain non
      hemolytic streptococci into rabbits; but evidence in support of this
      interpretation of the reaction has not been obtained. The facts make it seem
      probable that if this secondary reaction is due to a hypersensitive state it must
      be one more closely allied to the tuberculin reaction than to the Arthus
      phenomenon.

PMID- 19869174
TI  - THE FILLING AND EMPTYING OF THE GALL BLADDER.
AB  - As a result of the control of the flow of bile into the duodenum largely by tonus
      and movements of the duodenum, bile intermittently enters the gall bladder where
      it is concentrated and undergoes other changes. The gall bladder empties itself
      of its content through the cystic duct (1) by the washing out of its contents by
      bile from the liver, (2) by the elasticity or contractile mechanism of its walls,
      and (3) by variations of intraabdominal pressure due to respiratory movements,
      contiguous organs, etc. A fourth manner of emptying of the gall bladder is by
      absorption of a portion of its content through its walls. The gall bladder is
      never entirely empty but tends to come to a state of partial collapse, when its
      contents are under minimum pressure. We have been unable to demonstrate rhythmic
      contractions of the gall bladder due to its musculature. If they are present they
      may aid but they are not essential for its emptying or filling. Experimentally,
      in the dog, a rubber bag which was substituted for the gall bladder functioned in
      a manner very similar to that of the normal gall bladder as shown by
      cholecystographic studies. The concentrating function, however, was absent.

PMID- 19869175
TI  - THE RELATION OF THE RETICULO-ENDOTHELIAL SYSTEM TO THE BLOOD PLATELET COUNT.
AB  - 1. So called blockade of the reticulo-endothelial system results in a marked
      increase in the platelet count. 2. The count rapidly becomes very high, shows a
      sharp partial recoil and then a gradual diminution even though the blockade be
      continued. 3. The mechanism regulating the number of platelets is a complicated
      one. 4. Apparently phagocytosis by cells of the reticulo-endothelial system is
      not the only means by which blood platelets are destroyed.

PMID- 19869176
TI  - RELATION BETWEEN ORGAN WEIGHTS AND OBSCURE LESIONS IN APPARENTLY NORMAL RABBITS :
      SECOND PAPER.
AB  - A study of organ weights was made on a group of 295 normal rabbits for the
      purpose of determining whether any relation could be detected between the weights
      of organs and the extent and activity of the lesions found post mortem. The
      results obtained seemed to indicate that disease, even in its mildest form, is
      capable of affecting the weights of organs that are not directly involved by the
      disease process and that the effect produced bears a relation to both the extent
      and the activity of the lesions present. There was also some evidence that the
      converse might be true; namely, that the occurrence and subsequent course of
      disease may be influenced in some measure by the state of organ balance and the
      ability of the animal organism to adjust itself to meet the demands of disease
      producing agencies.

PMID- 19869177
TI  - THE EFFECT OF MECHANICAL TENSION UPON THE POLARITY OF GROWING FIBROBLASTS.
AB  - These experiments seem to justify the conclusion that mechanical tension may
      determine the polarity of cell division and line of growth of developing
      fibroblasts, and further that a shift in tension may cause a shift in position of
      fibroblasts already formed.

PMID- 19869178
TI  - THE PHYSIOLOGICAL VARIATIONS IN RESISTANCE TO BILE FLOW TO THE INTESTINE.
AB  - Under specially controlled conditions in the healthy unanesthetized dog we have
      measured the resistance offered to the flow of bile through the lower common
      duct. The average resistance 4 to 12 hours after a feeding was found to
      correspond to the pressure of a column of bile 100 to 120 mm. in height. After a
      24 to 72 hour fast the resistance was such as to support a much higher column of
      bile, one of 300 mm. at times. The exhibition of food to the fasting animal
      usually precipitated a reflex lessening in the resistance to the flow of bile to
      the intestine, the actual taking of food always brought it about. This was
      transient and was soon followed by a period of increased resistance lasting 10 to
      30 minutes after food had entered the stomach. There succeeded a drop in
      resistance which was gradual and fluctuating. We have observed an increase in the
      resistance to the flow of bile into the intestine after alkali has entered the
      stomach, and a decrease after acid has been administered. We attribute the sudden
      changes chiefly to the activity of the sphincter of Oddi.

PMID- 19869179
TI  - ON THE EXPULSION OF BILE BY THE GALL BLADDER; AND A RECIPROCAL RELATIONSHIP WITH
      THE SPHINCTER ACTIVITY.
AB  - After feeding a dog, forceful contractions of the gall bladder occur that are
      sufficient in strength to expel part of the contents of the viscus against a
      considerable pressure resistance. The pressure within the gall bladder of a
      healthy, unanesthetized dog fasted 24 to 48 hours is usually about equal to a
      column of bile 100 mm. high. After a few swallows of food there is a rapid
      increase in the pressure to more than 200 mm. with a gradual fall in it again,
      and repeated similar rises and falls occur thereafter. The gall bladder
      contractions responsible for these alterations are accompanied by a lessening in
      the resistance to the passage of bile to the intestine, a resistance which is
      maintained by the muscles at the lower end of the common duct. There would appear
      to be a reciprocal response on the part of the two structures to the one
      stimulus. The maximum pressure developing within the temporarily obstructed
      biliary tract in an animal with the gall bladder excluded about equals that of a
      column of bile slightly more than 300 mm. in height. The taking of food acts as a
      stimulus on the rate of bile secretion, but does not alter the maximum secretion
      pressure. When the gall bladder is connected with the duct system, obstruction
      does not lead until after some hours to the development of a pressure of more
      than 100 to 150 mm. within the biliary tract,-that is to say the pressure does
      not rise above the normal. Its failure to rise further is referable to the
      activity of the gall bladder to store and concentrate the bile as secreted. The
      physiological and clinical significance of these findings is discussed.

PMID- 19869180
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : I.
      PNEUMOCOCCUS HEMOTOXIN.
AB  - Pneumococcus hemotoxin, an antigenic substance of bacterial origin, is converted
      by oxidation to a product devoid of hemolytic action. The oxidation product of
      the hemotoxin may be converted to the original hemolytic substance by reduction,
      by the anaerobic action of certain bacteria, or by sodium hydrosulfite. The
      active lysin, or hemotoxin, produced by the reduction of the inactive oxidized
      extracts is identical with the original, active, reduced hemotoxin; it possesses
      the same degree of thermolability and is neutralized by the same specific
      antibody. The inactive products formed by heating the hemotoxin anaerobically
      cannot be "reactivated" by reducing agents. The immunological significance of
      these relations will be discussed in a subsequent paper.

PMID- 19869181
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : II. THE
      HEMOTOXIN OF THE WELCH BACILLUS.
AB  - A study has been made of the oxidation and reduction of the hemotoxin of the
      Welch bacillus. The oxidation of the lysin results in the loss of its hemolytic
      activity. The "inactive" oxidation product of the Welch lysin may be reversed to
      the "active" lysin by treatment with biological or chemical reducing agents. The
      lysin, both in its reduced and oxidized form, is irreversibly inactivated by the
      same heat treatment. The pH of the system is an important factor in the oxidation
      of the lysin, the process proceeding much more rapidly at a pH above 7.0.

PMID- 19869182
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : III.
      TETANOLYSIN.
AB  - A preliminary study was made of the rate of formation of tetanolysis and of the
      effect of glucose upon the lysin production. The heat lability of tetanolysin was
      next compared with that of the lysins of other bacteria. Finally the methods used
      to estimate the relative amounts of "active" hemoglobin and its "inactive"
      derivatives in deteriorated solutions of blood pigments were applied to the
      differentiation of the various derivatives of "active" tetanolysin present in
      deteriorated culture fluids.

PMID- 19869183
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : IV.
      STREPTOLYSIN.
AB  - The "spontaneous deterioration" of streptolysin has been studied by the methods
      already used in investigations of the oxidation-reduction of blood pigments and
      of the lysins of other bacteria. From the results of this study, it may be
      concluded that the commonly observed "spontaneous deterioration" of streptolysin
      consists in the conversion of the originally active lysin to a hemolytically
      inactive oxidation product. This process is a reversible one, and the activity of
      the lysin is restored by reduction.

PMID- 19869184
TI  - THE FUNDAMENTAL PROPERTIES OF THE FIBROBLAST AND THE MACROPHAGE : I. THE
      FIBROBLAST.

PMID- 19869185
TI  - THE FUNDAMENTAL PROPERTIES OF THE FIBROBLAST AND THE MACROPHAGE : II. THE
      MACROPHAGE.
AB  - 1. Monocytes and tissue macrophages become identical in appearance when they live
      under identical conditions. Macrophages cultivated in nutrient and non-nutrient
      media acquire different structures. Monocytes and tissue macrophages are mere
      functional variations of a single type. 2. The structure of the segregation
      apparatus and of the mitochondria of monocytes and macrophages depends on the
      composition of the pericellular fluid and on the metabolic state of the cells. 3.
      The monocyte and the macrophage are endowed with a number of physiological
      properties which become apparent when they grow in pure cultures. 4. The
      knowledge of these fundamental characteristics explains the behavior of the cells
      within the organism.

PMID- 19869186
TI  - COMPARATIVE STUDIES OF HERPETOMONADS AND LEISHMANIAS : I. CULTIVATION OF
      HERPETOMONADS FROM INSECTS AND PLANTS.
AB  - Nine strains of herpetomonads have been isolated in pure culture from eight
      varieties of insects, and three strains from two species of plants. Four of the
      cultures were derived from latex-feeding insects (Oncopeltus fasciatus,
      Oncopeltus sp. ?, Lygaeus kalmii) and three from latex plants (Asclepias syriaca,
      Asclepias nivea), two from mosquitoes (Culex pipiens and Anopheles
      quadrimaculatus), one from the house fly (Musca domestica), and two from
      bluebottle flies. In addition impure cultures have been obtained from Oncopeltus
      cingulifer and from its plant host, Asclepias curassavica. The flagellates
      cultivated, all of which belong to the genus Herpetomonas, have been identified
      chiefly by their biological relationships, which will be described in detail in
      Part II of this report. The seven strains from latex-feeding insects and latex
      plants represent two distinct species, which have been designated H. oncopelti
      and H. lygaegorum. The two strains from mosquitoes proved to be the same organism
      and have been called Herpetomonas culicidarum. The culture obtained from Musca
      domestica contained larger individuals than those of any other strain, and the
      organism is morphologically distinct from either of the Calliphora strains. None
      of the fly flagellates cultivated could be identified with the. species H. muscae
      domesticae or H. calliphorae, and hence they have been given new names,
      Herpetomonas muscidarum, H. media, and H. parva. Blood agar plates were used for
      initial cultivation of the strains from insects and the semisolid leptospira
      medium for isolation of the plant flagellates. A number of the strains were
      purified by plating on acid blood agar, a procedure which reduces considerably
      the growth of bacterial contaminants. The Barber technique was utilized for
      isolation of the flagellates from flies, because of the very large number of
      bacteria found with them in these insects, and, in one or two instances, for the
      purification of impure cultures. Once they have been obtained in culture, all the
      strains grow well on leptospira medium, as well as on blood slants. Growth takes
      place both at 26 degrees C. and at 37 degrees . The morphology of the organisms
      is considerably modified by cultivation. This is especially true of the plant
      flagellates. In the latex they have ribbon-like bodies, often twisted, and
      comparatively short flagella; the protoplasm is clear, almost hyaline. The
      flagellates seen in the gut and feces of insects are usually large, slender
      organisms, with flagella as long as or even longer than the body, which contains
      numerous volutin granules in the cytoplasm. In cultures under parallel conditions
      the flagellates from both these sources become shorter and thicker, the plant
      forms no longer appear flat and ribbon-like, and in general the organisms
      approach one another in morphological features. Even in the case of the least
      modified insect flagellates, i.e. those from flies, there is never exact
      correspondence between the natural and the cultivated forms. The morphological
      features of the cultivated flagellates vary according to the medium on which the
      organisms are grown and the age of the culture. The flagellates grown on the
      surface of blood slants are pyriform, with truncated anterior portion, and short
      flagellum; in the condensation water, however, the individuals are elongated and
      have long active flagella. On the leptospira medium the slender active forms with
      long flagella predominate. In the presence of fermentable carbohydrate, or in
      medium containing considerable acid, peculiar bifurcated or multifurcated
      individuals are seen. Similar forms have been seen under natural conditions.
      Cultures of Leishmania behave in the same way under the conditions described.
      There is a striking difference in rapidity of growth between the organisms
      isolated by us and the leishmanias, H. ctenocephali, and T. rotatorium. While the
      stock cultures of the group first mentioned multiply rapidly at 37 degrees C.,
      growth becoming visible within 24 hours, the latter group grow scarcely at all at
      37 degrees and only slowly at 25 degrees , 1 to 2 weeks being required for growth
      to become macroscopically demonstrable. While the flagellum of the leishmanias,
      as also of H. ctenocephali, is long, serpentine in its movements, and heavy,
      having the appearance of being enveloped by a sheath throughout its entire
      length, that of the recently isolated strains is thin, less flexible, and without
      the sheathlike appearance. The only exceptions to this rule are the flagellates
      from Musca domestica and Calliphora No. 1, which have a long flagellum not unlike
      that of the leishmanias. As the foregoing observations indicate, morphological
      differentiation of the flagellates studied, while not impossible, is subject to
      error by reason of the variations due to age and cultural conditions. The
      flagellates of the latex-feeding insects, the plants, the flies, and the
      mosquitoes can readily be distinguished from Leishmania by their rapid growth at
      37 degrees C., but their differentiation from one another is possible only by
      serological and fermentation reactions.

PMID- 19869187
TI  - COMPARATIVE STUDIES OF HERPETOMONADS AND LEISHMANIAS : II. DIFFERENTIATION OF THE
      ORGANISMS BY SEROLOGICAL REACTIONS AND FERMENTATION TESTS.
AB  - Serological reactions and fermentation tests have been employed in the present
      investigation as a means of differentiating various strains of herpetomonads from
      one another as well as from leishmanias. The twelve strains of herpetomonads
      isolated from insects and plants all proved to be serologically unrelated to any
      of the leishmanias, and were distinguishable from them by the manner in which
      they affected various carbohydrates. Three of the strains of herpetomonads tested
      had been isolated from milkweeds (Asclepias syriaca and A. nivea) and four from
      bugs which feed on the latices of these plants (Oncopeltus fasciatus, Oncopeltus
      sp.? from Peru, and Lygaeus kalmii). When tested for their serological and
      carbohydrate-fermenting properties, however, the seven strains proved to be of
      two kinds only, one represented by the strain first isolated from Oncopeltus
      fasciatus) and hence named H. oncofelti, the other by H. lygaeorum, so named
      because it was first isolated from Lygaeus kalmii. Serologically there was a
      certain degree of group reaction among the flagellates of these two types, but in
      their action upon carbohydrates they were entirely different, H. oncopelti
      splitting thirteen carbohydrates, H. lygaeorum only three. Three strains of
      herpetomonads isolated from flies proved to be distinct both in serological
      properties and in their action upon carbohydrates. One, derived from the house
      fly, and called H. muscidarum, was able to ferment most of the carbohydrates
      tested, including lactose which was not affected by any of the other strains. The
      other two, isolated from bluebottle flies, behaved much the same as the
      leishmanias with regard to carbohydrate fermentation, attacking five of the same
      sugars. One of them fermented galactose in addition, the other both galactose and
      inulin. Two strains from mosquitoes (Anopheles and Culex) behaved identically in
      serological reactions and also in fermentation tests. They are regarded as one
      species and have been named H. culicidarum. This organism ferments thirteen
      sugars, including amygdalin which no other organism of the series attacks. One of
      the most striking phenomena observed was the entire lack of fermentative faculty
      on the part of Herpetomonas ctenocephali and Trypanosoma rotatorium. Neither of
      these organisms was affected by any of the immune sera prepared with other
      flagellates. The serological specificity of Leishmania tropica, L. brasiliensis,
      and L. donovani, and the close relation between L. donovani and L. infantum were
      confirmed in the present study. These organisms could not, however, be
      differentiated by fermentation tests. The data presented suggest that the
      biological characteristics of flagellates of the Herpetomonas group may be
      utilized with advantage for identification of a species which occurs in different
      environments and for separation of different species when they are found in the
      same environment. If the leishmania parasites pass the flagellated or
      herpetomonad stage of their life history in some invertebrate host, it may be
      possible by tests of the sort described to distinguish them from the non
      pathogenic herpetomonads which are so widely distributed among insects and
      plants.

PMID- 19869188
TI  - STUDIES ON X-RAY EFFECTS : XV. THE PREVENTION OF PIGMENT FORMATION IN THE HAIR
      FOLLICLES OF COLORED MICE WITH HIGH VOLTAGE X-RAY.
AB  - 1. Hard x-rays prevent the formation of pigment in the hair follicles of mice,
      with result that hair previously black comes in white. 2. Exposure of the ventral
      side of a mouse to the x-rays causes the hair on the back to come in white about
      40 to 50 days after it has whitened the hairs on the abdomen.

PMID- 19869189
TI  - BIOLOGY OF BACTERIUM LEPISEPTICUM : III. PHYSICAL, CULTURAL, AND GROWTH
      CHARACTERISTICS OF DIFFUSE AND MUCOID TYPES AND THEIR VARIANTS.
AB  - 1. From 1922 to 1926, mucoid types of Bact. lepisepticum have proved more
      prevalent that "D" types in certain rabbit communities. 2. The bacteria from the
      mucoid colonies are larger than the "D" type; "G" variants are very small. All
      types are largest during the period of logarithmic growth. Differences in size
      appear to be determined chiefly by the amount of "cytoplasmic" substance. 3. The
      mucoid colony is larger and appears watery as compared with the "D" colony. 4.
      Fermentation tests, indole and nitrate reduction reactions of mucoid and "D"
      types and their variants are similar. 5. The acid agglutination zone of the
      mucoid type is similar to that of the "D" type. 6. The mucoid type is more stable
      in suspension than the "D" type. 7. The negative potential of mucoid types is
      similar to that of the "D" and higher than that of "G" variants. 8. The behavior
      of the mucoid type of bacilli in fluid media differs from that of the "D" strains
      in the following respects. About 500 or more mucoid organisms per c., inoculated
      into plain broth, will grow; "D" strains require seedings of at least 100,000. A
      lag of 3 to 48 hours duration occurs in the growth of mucoid strains, according
      to the amount of original seeding. This is considerably longer than that observed
      for the "D" strains. The period of multiplication is relatively long-24 to 48
      hours-and the maximum number per cc. does not exceed 600,000,000. "D" strains
      reach 1,000,000,000 per cc. within 24 hours. "G" variants appear very slowly in
      mucoid cultures as contrasted with "D" strains, where their occurrence is rapid
      and abundant. The presence in the broth of blood or other oxygen-absorbing
      substances enables less than ten mucoid organisms per cc. to multiply without lag
      and to reach a maximum number of about 600,000,000 per cc. in 24 to 48 hours. "D"
      strains reach a count of 1,000,000,000 per cc. within 12 hours under similar
      conditions. 9. "D" and mucoid strains, inoculated into 750 cc. of plain or blood
      broth, and incubated at 37 degrees , remain alive for more than 12 months. The
      numbers per cc. decrease to about 1/1000 of the maximum after the first 6 weeks.
      Subsequently, the rate of decrease is slower. The original strains are gradually
      replaced by "intermediate" and "G" colonies. 10. The various mucoid strains
      proved similar in their antigenic properties. "D" strains were also mutually
      related, but no cross-agglutination between "D" and mucoid types was
      demonstrable.

PMID- 19869190
TI  - BIOLOGY OF BACTERIUM LEPISEPTICUM : IV. VIRULENCE OF DIFFUSE AND MUCOID TYPES AND
      THEIR VARIANTS.
AB  - As a preface to a general discussion of these experiments, we wish to refer again
      briefly to the titrations of virulence described in this paper. None of them was
      carried out in an altogether proper manner,- it was necessary to employ rabbits
      of mixed breed, to use small numbers, and in some instances, to compare the
      results of titrations done at different times of the year. Furthermore, many
      tests were made in the mouse, a foreign host, and by means of artificial
      injection into the peritoneal cavity. Hence, if our results had shown
      fluctuations and wide differences, we should have experienced difficulty in
      interpreting their significance. Fortunately, however, the control measures which
      we were able to employ,-namely the utilization of animals of similar age and
      weight, bred at the Rockefeller Institute under uniform environmental conditions,
      and free of previous exposure to Bact. lepisepticum, together with the technique
      of intranasal instillation of similar doses,-were sufficient to give consistent
      and relatively uniform effects. These we have regarded as presumptive evidence of
      the following: (1) that of the three types of Bact. lepisepticum described, "D"
      strains are the most virulent or pathogenic, mucoid forms less so, and "Grdquo;
      types little or not at all virulent; (2) that different strains of the same type
      are of similar virulence; and (3) that passage of type-pure strains through non
      toxic, nutrient media, or through animals, does not modify their virulence. The
      experiments described in the present communications were planned to investigate
      certain microbic factors which seem to influence the spread of Bact. lepisepticum
      infection. Accordingly, we studied the types encountered in nature, their
      behavior in the rabbit host, and other qualities which might possibly be related
      to their parasitic activities. At the outset we discovered that very little is
      known about the "Pasteurella" or "hemorrhagic septicemia" organisms. Every small,
      blunt bacillus with bipolar granules and certain quite definite fermentative
      reactions is placed in this group and is further designated by prefixing the name
      of the animal from which it was obtained. Differentiation on the basis of
      serological studies has been extremely difficult and as yet not sufficiently
      detailed and complete to be of use. We have, therefore, called our strains "Bact.
      lepisepticum," because they belong to the Pasteurella group and were obtained
      from rabbits, but at the same time have recognized the possibility that similar
      forms may also be present in other animal hosts. The "D" and mucoid types may or
      may not be mutually related. Each has its distinctive growth characteristics and
      antigenic properties, but these differences are not sufficient to exclude the
      possibility that the two types may have resulted from the action of bacteriophage
      or so called "mutation" phenomena upon a single "parent" strain. We have
      attempted to explain the difference in natural prevalence of "D" and mucoid types
      in terms of virulence and vegetative capacity (1, a, d). Thus we find that "D"
      types are at present rarely encountered in rabbits, while the mucoid forms are
      widespread. The former prove to be highly virulent and slightly vegetative; the
      latter, less virulent and readily vegetative. The same inverse relationship
      between virulence and prevalence obtains in human diphtheria (7) and pneumococcus
      infections (8);-virulent Type I and II pneurnococci and diphtheria bacteria are
      relatively uncommon in carriers, while the less pathogenic diphtheria forms and
      Type III and IV pneumococci are widespread. It is possible, therefore, that in
      these respiratory diseases the virulent types of bacteria are transients, unable
      to survive in a community except at epidemic times, while the less pathogenic
      types are more adapted to a parasitic existence in the tissues of a considerable
      percentage of a population (9). Just what properties of bacteria are responsible
      for their ability to kill or to survive indefinitely in the surface tissue of an
      animal has not been determined. We find that physical properties such as
      agglutinability in acid buffer solutions, stability in suspension, and potential,
      bear no consistent relationship to virulence and vegetative capacity. Qualitative
      fermentation and indole reactions, likewise, gave no significant results.
      Experiments relating to comparative growth rates and nutritional requirements
      have, however, shown the following differences: Virulent "D" types were found to
      require a medium with relatively low oxygen tension and these multiplied with
      extreme rapidity; mucoid types were less exacting and grew more slowly; while "G"
      variants needed no accessory substances for good growth. Hence, there may prove
      to be some relation between food supply, metabolic activity, and pathogenicity;
      bacteria may be parasitic or saprophytic because of their own specific
      nutritional requirements, and may be virulent in one host and not in another
      because of chemical differences in the available food. It will be interesting to
      test the validity of these suggestions by further experiment. We may summarize
      the results of this investigation as follows. A "D" and a "mucoid" type of
      Pasteurella organisms have been recovered from rabbits; the former is relatively
      rare, is virulent, and not vegetative; the latter is very common, less virulent,
      and readily adaptable to a vegetative existence. The virulence of the different
      strains of each type appears to be about the same and not to be affected by
      passage through animals or non-toxic, nutrient media. Although each possesses
      distinctive and constant characteristics, we feel that the possibility of mutual
      relationship has not been entirely excluded. Investigation of bacterial
      properties associated with virulence has as yet given no definite and positive
      results.

PMID- 19869191
TI  - ACTION ON FIBROBLASTS OF THE PROTEIN FRACTION OF EMBRYONIC TISSUE EXTRACT.
AB  - The above experiments indicate that the growth-stimulating substance found in
      embryonic tissue extract, which has been responsible for the continuous growth of
      fibroblasts in vitro for 14 years, is either protein in nature or closely
      associated with the protein of the extract and adsorbed by it. If any specific
      hormone responsible for cell division is present, it is united to the protein or
      carried along with it in its first precipitation. It seems probable that the
      tissues utilize this protein for the nitrogen which they build into protoplasm.
      Whether it is first hydrolyzed before adsorption by the tissues has not been
      ascertained as yet. It has been shown in other experiments reported in the
      following paper that the amino acids of the tissue juice do not suffice for the
      growth of fibroblasts and that hydrolyzed tissue juice is toxic in the same way
      that a too concentrated mixture of amino acids is toxic. The results of the
      foregoing experiments may be summarized as follows: 1. Fractionation of embryo
      tissue juice has shown that it is the protein fraction that contains the
      activating substance. 2. Tissues continue to grow for a long time in the protein
      of the extract precipitated by CO(2) and at a rate approximately equal to that in
      the original extract diluted to the same nitrogen concentration. 3. The non
      protein nitrogen gives slight stimulation to growth. 4. Purification of the
      protein by repeated precipitation destroys its growth-promoting properties, but
      whether this is due to a denaturing of the protein,-which occurs very readily,-or
      to loss of some substance possibly an enzyme attached to it, has not been
      ascertained. 5. Preparations of purified proteins from embryonic tissue and egg
      white have shown no marked nutritive or stimulating action. A number of other
      pure substances have been tried without effect.

PMID- 19869192
TI  - EFFECT OF THE AMINO ACIDS AND DIALYZABLE CONSTITUENTS OF EMBRYONIC TISSUE JUICE
      ON THE GROWTH OF FIBROBLASTS.
AB  - The ultrafilterable constituents of embryonic tissue extract are unable to
      support cell life in vitro. They stimulate cell migration and possibly
      multiplication, without increasing the mass of the tissue. Embryonic tissue
      extract freed from amino acids by dialysis still retains a considerable part of
      its growth-promoting properties. The area of growth of tissues in embryonic
      tissue extract free from amino acids is appreciably less than that with the whole
      extract, probably owing to the denaturation of part of the protein, or perhaps to
      the inactivation or loss of an enzyme. The addition of either the ultrafilterable
      components or an artificial mixture of amino acids to this dialyzed extract
      increases the area of cell migration but does not restore all the activity lost
      on dialysis. The observed differences in growth of tissue, due to the addition or
      removal of dialyzable and ultrafilterable constituents of the extract, prove that
      the amino acids produce a more active cell migration and possibly multiplication,
      but no building up of new protoplasm.

PMID- 19869193
TI  - SUSCEPTIBILITY AND RESISTANCE TO TRYPANOSOME INFECTION : II. THE RELATION OF
      PHYSICAL ENVIRONMENT TO HOST SUSCEPTIBILITY TO INFECTION.

PMID- 19869194
TI  - THE VISCOSITY OF THE BLOOD OF THE DOG AFTER OBSTRUCTION OF THE UPPER
      GASTROINTESTINAL TRACT.
AB  - Estimations of the viscosity of the whole blood and plasma of the dog after
      experimental upper gastrointestinal tract obstruction are reported. With cardiac
      obstruction there is a rapid and marked rise in the viscosity of the whole blood
      and some increase in the viscosity of the plasma. The changes after pyloric
      obstruction are similar to those observed after cardiac obstruction. After
      obstruction of the upper jejunum only slight changes are observed. The increase
      in viscosity parallels quite closely the degree of the toxemia. It is
      unaccompanied by any marked concentration of the blood.

PMID- 19869195
TI  - SURFACE TENSION OF THE BLOOD SERUM OF THE DOG AFTER UPPER GASTROINTESTINAL TRACT
      OBSTRUCTION.
AB  - After obstruction of the upper gastrointestinal tract the surface tension of the
      blood serum of the dog shows no marked change. There is a tendency of the time
      drop to increase 24 hours after operation. There is no characteristic course of
      the time-drop.

PMID- 19869196
TI  - THE SEDIMENTATION RATE OF THE ERYTHROCYTES IN EXPERIMENTAL OBSTRUCTION OF THE
      GASTROINTESTINAL TRACT.
AB  - The results of the study of the suspension stability of the blood after upper
      gastrointestinal tract obstruction are reported. After obstruction of the cardiac
      end of the stomach, of the pylorus, and of the jejunum the red cells separate
      from the plasma much more rapidly than normal. The variation in sedimentation
      time is due to a variation in the physicochemical status of the blood.

PMID- 19869197
TI  - THE CHLORIDE CONTENT OF THE TISSUES OF THE DOG AFTER EXPERIMENTAL
      GASTROINTESTINAL TRACT OBSTRUCTION.
AB  - Comparative observations are reported on the chloride content of the blood,
      liver, and muscle of the dog after obstruction of the upper gastrointestinal
      tract. After obstruction of the pylorus there is a marked fall in the chloride
      content of the liver, and a slight fall in the muscle. Similar changes are
      observed after obstruction of the jejunum. With obstruction of the cardiac end of
      the stomach no change was observed.

PMID- 19869198
TI  - STUDIES ON THE BIOLOGY OF STREPTOCOCCUS : VI. BIOLOGY OF HEMOLYTIC STREPTOCOCCUS:
      ANTIGENIC RELATIONSHIPS BETWEEN STRAINS OF THE SCARLATINAL AND ERYSIPELAS GROUPS.
AB  - The interpretation of the results in these experiments is difficult on account of
      the variations in the physical capacity of different strains of hemolytic
      streptococcus to agglutinate and absorb agglutinin. Even when the antigens for
      agglutination and absorption are standardized and sera are carefully titrated
      variations in agglutination occur with different strains and sera. Variations may
      occur because of differences in the titer of the immune sera employed. In a large
      series of reactions with the same sera and strains, errors in interpretation
      depending on these factors can be eliminated because strains which agglutinate
      poorly will consistently give weak reaction with all sera, and weak sera will
      agglutinate all strains poorly. after such variations See PDF for Structure in
      agglutination are eliminated, if a strain varies grossly in agglutination with
      different sera, or the titer of different sera varies with the same strain as in
      Tables I to III, variations which occur must represent antigenic dissimilarities.
      We have previously commented on the dissimilarity of the individual strains in
      the scarlatinal and erysipelas groups. Although the strains within each of the
      groups are related they are seldom identical. This individuality of the strain
      was indicated by the fact that absorption by heterologous strains failed to
      absorb the agglutinin for the strain homologous with the serum. This strain
      individuality is again apparent in Tables I to III. Doses of heterologous strains
      equivalent to the unit absorptive dose which has already been defined, fail to
      remove the agglutinin for the homologous strain. This dose is sufficient however,
      to absorb the agglutinin for practically all heterologous strains. It appears
      from this observation that the strain specificity dominates the group
      specificity. Between the unit absorptive dose and a dose which is approximately
      0.2 to 0.3 of this unit, is a zone of great variation in absorption and
      agglutination. Below this zone absorption is complete for few strains. The
      differences in titer of various strains and absorbed sera in the zone where
      variations occur are very definite. For example in Table II, Strain E IX
      agglutinates well in Serum II absorbed with Strains E I and E III but poorly in
      serum absorbed with Strain E II. Numerous similar examples may be found. In a few
      instances heterologous strains agglutinate nearly as well as the homologous
      strains in these absorbed sera. Such strains probably resemble the homologous
      strains closely. These resemblances are not confined to the erysipelas strains
      but occur among the scarlet strains which agglutinate in erysipelas sera.
      Apparently it is impo-ssible to distinguish such scarlatinal strains from
      erysipelas strains by absorption of agglutinin. The relationship shown by these
      absorption tests is additional evidence in favor of the mosaic nature of the
      antigen. Strains of streptococcus of the erysipelas groups are apparently
      composed of several agglutinogenic fractions. If the antigen of a strain is made
      up of the fractions A, B, C, D, and E, serum for that strain would contain A, B,
      C, D, and E agglutinins. If this serum were absorbed with the homologous strain
      or an identical heterologous strain the agglutinin would be completely absorbed.
      On the other hand a qualitative or quantitative difference between the two
      strains would be apparent in the absorption and agglutination reactions. Such
      differences are evident in Tables I to III. This serum would agglutinate any
      strain containing any one or several of the fractions, but absorption of the
      serum by such a strain would leave fractions of the agglutinin in the serum. This
      absorbed serum would agglutinate the homologous strain. Heterologous strains
      would agglutinate if fractions remained in the serum corresponding to their
      antigenic components. Hence the reactions in the absorbed serum would depend on
      the qualitative and quantitative relationships between the component fractions in
      the serum, the absorbing strain, and the strains agglutinated. This conception of
      multiple antigens is not new in bacteriology. Durham (3) explained the reactions
      in the colon-typhoid group of bacilli on this basis. More recently Durand and
      Sedallian (4), and Andrewes, Derick, and Swift (5) have expressed the opinion
      that the agglutination reactions with hemolytic streptococcus can only be
      accounted for in this way. In many respects the reactions observed with the colon
      typhoid group of Gram-negative bacilli resemble those experienced with the
      erysipelas and scarlatinal groups of hemolytic streptococcus. Apparently we have
      exhausted the possibilities of studying these groups further by agglutination and
      absorption. Our knowledge regarding the specificity and relationship of the
      antigenic fractions must come from the study of fractions isolated and refined by
      chemical methods.

PMID- 19869199
TI  - EFFECTS OF LIGHT ON NORMAL RABBITS, WITH ESPECIAL REFERENCE TO THE ORGANIC
      REACTION : I. CLINICAL AND POSTMORTEM OBSERVATIONS.
AB  - A group of 50 normal male rabbits kept under conditions of constant light that
      had none of the shorter ultra-violet rays and another group kept in constant
      darkness for 2 to 12 weeks were observed clinically and subjected to postmortem
      examination for the purpose of determining the effect of these environmental
      conditions upon general body health and the weights of organs. A similar group of
      50 rabbits caged in an ordinary animal room for the same period, and two groups
      of 40 and 20 rabbits respectively, which had recently been brought into the
      laboratory, served as controls. It was found that the general health of the
      rabbits was not impaired by the artificial light or the exclusion of light. The
      gain in body weight which occurred in all groups was especially marked in the
      case of those kept under conditions of constant light. The incidence of
      spontaneous disease recognizable clinically during the experiment was extremely
      low and of a mild character and did not obviously disturb the health of the
      animal. It was found at postmortem examination, on the other hand, that 59.3 per
      cent of the rabbits caged indoors, that is in the light, dark, or unaltered
      rooms, and 58.3 per cent of those recently brought to the laboratory had visible
      lesions of some kind. The great majority of these lesions, however, were of a
      slight grade, and none appeared to have any deleterious effects upon the general
      physical state of the animals.

PMID- 19869200
TI  - EFFECTS OF LIGHT ON NORMAL RABBITS, WITH ESPECIAL REFERENCE TO THE ORGANIC
      REACTION : II. ORGAN WEIGHTS.

PMID- 19869201
TI  - EFFECTS OF LIGHT ON NORMAL RABBITS, WITH ESPECIAL REFERENCE TO THE ORGANIC
      REACTION : III. ANALYSIS OF ORGAN WEIGHTS.
AB  - An analysis has been made of the organ weights of normal rabbits exposed to a
      constant illumination having none of the shorter ultraviolet rays and of other
      rabbits kept in darkness for periods of 2 to 12 weeks. The environment of
      constant illumination was associated with a well marked decrease in the relative
      weights of most organs, and in certain instances this occurred when the organ
      weights of the controls were becoming increasingly large. There was also an
      associated effect of stabilization of organ weight. The majority of the organs of
      rabbits caged in constant darkness also showed a tendency toward decreased and
      stabilized weights, but these effects were less pronounced than in the rabbits
      caged under conditions of constant illumination. A notable exception to this
      general result was the weight of the liver which was markedly increased. The
      results of this experiment support the conception that there is a relationship
      between light and the physical state of the animal organism which may be
      expressed in the concrete form implied by the trend or direction of organ weight.

PMID- 19869202
TI  - THE CHEMICAL NATURE OF SUBSTANCES REQUIRED FOR CELL MULTIPLICATION.
AB  - 1. Fibroblasts and epithelial cells in pure culture obtain the nitrogen, which
      they build into protoplasm, from proteoses and possibly other primary derivatives
      of proteins. These proteoses have been prepared from embryo tissues, egg white,
      commercial fibrin, rabbit brain, Witte's peptone, etc. 2. The presence in embryo
      juice of a hormone that stimulates cell division is improbable. 3. Proteoses
      separated from peptic digests of fibrin by sodium sulfate determine a more
      abundant and prolonged multiplication of the fibroblasts than is produced by
      embryo juice. Peptones and the smaller split products appear to furnish some
      nutrient material, but do not cause the rapid proliferation characteristic of
      proteoses, and are sometimes toxic for tissue cells. 4. Possibly the effect of
      embryo juice on fibroblasts and epithelium is due to the splitting of the protein
      of the juice into proteoses by the cell enzymes, or by other enzymes activated by
      the presence of living cells.

PMID- 19869203
TI  - AUTOPLASTIC THYMUS TRANSPLANTS : II. WITH PARTICULAR REFERENCE TO THE
      REGENERATION OF THE RETICULUM CELLS AND THE FORMATION OF HASSALL'S CORPUSCLES.
AB  - 1. Regeneration of a thymus transplant is characterized by hypertrophy and
      hyperplasia of the reticulum cells, leading to the formation of small and large
      atypical Hassall bodies during the early stages. 2. Regeneration is usually
      complete by the 3rd week, when the newly formed lobules show differentiation into
      cortical and medullary zones, and typical Hassall bodies appear. 3. Typical
      Hassall's corpuscles are also derived from the reticulum epithelial cells. 4.
      These corpuscles have no function, being aggregates of spent reticulum cells. 5.
      The thymus reticulum cells are actively phagocytic, and react rapidly when
      noxious influences are exerted on the gland.

PMID- 19869204
TI  - ETIOLOGY OF OROYA FEVER : II. VIABILITY OF BARTONELLA BACILLIFORMIS IN CULTURES
      AND IN THE PRESERVED BLOOD AND AN EXCISED NODULE OF MACACUS RHESUS.
AB  - 1. Animals immunized with the formalinized filtrates of young toxic cultures of
      B. botulinus produce an antitoxic serum poor in precipitins. 2. Animals immunized
      with the formalinized filtrates of old and partly autolyzed toxic cultures
      produce an antitoxic serum containing precipitins. 3. Animals immunized with
      toxin-free autolyzed bacteria produce a serum free from antitoxin but rich in
      specific precipitins. 4. Animals immunized with the filtrates of an atoxic
      variant produce a serum free from antitoxin but rich in precipitins for the
      homologous toxin. 5. Animals immunized with the washed bacteria of the atoxic
      variant produce a serum that contains no antitoxin, but is rich in precipitins
      for the homologous toxin. 6. Removal of the precipitins by flocculation with a
      non-toxic antigen does not materially reduce the antitoxic value of a serum. 7.
      Removal of the proteins of the antigen by add coagulation removes the specific
      precipitable substance. 8. All the sera that contain precipitins produce the
      specific flocculus when combined with homologous toxins, anatoxins, or with the
      filtrates of the atoxic variant. The flocculation is restricted within the type.
      The amount of the precipitate and the width of the zone vary approximately with
      the estimated amount of bacterial protein in the antigen that is used for the
      immunization of animals. We conclude, therefore, that the toxin-antitoxin
      flocculation is a specific bacterial precipitation phenomenon.

PMID- 19869205
TI  - THE RELATION OF BACTERIUM PNEUMOSINTES TO INFLUENZA: A STUDY WITH A STRAIN OF THE
      ORGANISM DERIVED FROM THE NASOPHARYNGEAL WASHINGS OF A CASE OF INFLUENZA.
AB  - Nasopharyngeal washings from a case of epidemic influenza have proven capable of
      initiating a pathological change in rabbits and in guinea pigs characterized
      after an incubation period of 1 or 2 days, by some elevation of temperature,
      reduction in the number of circulating leucocytes, especially of the
      mononuclears, and by a pulmonary lesion during the period of reaction, which is
      distinguishable from those accidentally incurred at the time of death. From one
      such animal, in the second passage of the virus, an anaerobic coccobacius,
      corresponding in all respects to Bact. pneumosintes, was isolated by the method
      employed by Olitsky and Gates. This organism also proved capable of initiating
      the pathological change in animals found after inoculation with influenzal
      material. The observation of Olitsky and Gates that the presence of this organism
      in the lungs of experimental animals predisposes to pulmonary localization of
      other bacteria with the production of definite pneumonic lesions has been
      confirmed. Bact. pneumosintes infections may be induced by subcutaneous injection
      of infected material.

PMID- 19869206
TI  - THE NATURE OF THE TOXIN-ANTITOXIN FLOCCULATION PHENOMENON.
AB  - 1. Animals immunized with the formalinized filtrates of young toxic cultures of
      B. botulinus produce an antitoxic serum poor in precipitins. 2. Animals immunized
      with the formalinized filtrates of old and partly autolyzed toxic cultures
      produce an antitoxic serum containing precipitins. 3. Animals immunized with
      toxin-free autolyzed bacteria produce a serum free from antitoxin but rich in
      specific precipitins. 4. Animals immunized with the filtrates of an atoxic
      variant produce a serum free from antitoxin but rich in precipitins for the
      homologous toxin. 5. Animals immunized with the washed bacteria of the atoxic
      variant produce a serum that contains no antitoxin, but is rich in precipitins
      for the homologous toxin. 6. Removal of the precipitins by flocculation with a
      non-toxic antigen does not materially reduce the antitoxic value of a serum. 7.
      Removal of the proteins of the antigen by add coagulation removes the specific
      precipitable substance. 8. All the sera that contain precipitins produce the
      specific flocculus when combined with homologous toxins, anatoxins, or with the
      filtrates of the atoxic variant. The flocculation is restricted within the type.
      The amount of the precipitate and the width of the zone vary approximately with
      the estimated amount of bacterial protein in the antigen that is used for the
      immunization of animals. We conclude, therefore, that the toxin-antitoxin
      flocculation is a specific bacterial precipitation phenomenon.

PMID- 19869207
TI  - EXPERIMENTAL GLOMERULONEPHRITIS INDUCED IN RABBITS WITH THE ENDOTOXIC PRINCIPLE
      OF STREPTOCOCCUS SCARLATINAE.
AB  - 1. Broth-grown cultures, cultures from blood agar slants and culture filtrates
      (Berkefeld N or V) of H. Streptococcus scarlatinae are without appreciable effect
      upon the rabbit, no matter how large the dose or by what route introduced. 2. The
      active toxic principle of H. Streptococcus scarlatinae for rabbits is intimately
      associated with the protein of the bacterial cell, and is not given off in the
      artificial medium during the growth activity of the organism, indicating,
      therefore, its endotoxic character. 3. The endotoxin is readily obtained from the
      viable scarlatinal cultures through the medium of the peritoneal cavity of the
      rabbit immunized against the homologous strain (Pfeiffer phenomenon). The toxic
      substance thus obtained we have termed a lysate. 4. The rabbit is highly
      susceptible to the in vivo prepared lysate of Streptococcus scarlatinae, at least
      from the cultures we have employed. The degree of the toxic effect upon the
      rabbit depends upon the size of the dose and the route through which it is
      introduced. The specific effects range from mild to severe and fatal forms of
      toxemia as indicated by high fever, leucocytosis, paralysis and acute hemorrhagic
      glomerular nephritis. 5. The experimentally induced nephritic lesions are
      analogous in kind and variety to those of acute scarlatinal nephritis in man,
      including the "epithelial crescent" formation, hyaline thrombi of glomerular
      capillaries, hemorrhage into capsular space and necrosis of capillary tufts.

PMID- 19869208
TI  - SUSCEPTIBILITY OF RABBITS TO INFECTION BY THE INHALATION OF VIRULENT PNEUMOCOCCI.
AB  - 1. Rabbits are very susceptible to infection by inhalation of Type I pneumococci.
      2. When rabbits are exposed to a pneumococcus spray the bacteria readily
      penetrate into the lower respiratory tract. The pneumococci which reach the
      periphery of the lungs as a result of this procedure usually disappear within a
      few hours but a generalized and fatal septicemia frequently later appears.
      Pneumococci may then be recovered from the periphery of the kidney, liver, and
      spleen. In the animals which die pleurisy and pericarditis are common but
      pneumonia does not occur. 3. Rabbits may recover from pneumococcus septicemia.

PMID- 19869209
TI  - STUDIES IN EXPERIMENTAL SYPHILIS : VI. ON VARIATIONS IN THE RESPONSE OF TREATED
      RABBITS TO REINOCULATION; AND ON CRYPTOGENETIC REINFECTION WITH SYPHILIS.
AB  - Syphilitic rabbits inoculated intratesticularly and treated with arsphenamine
      before the 69th day of the disease, when reinoculated with the same strain of
      treponemata and in a manner identical with that of the first inoculation) are
      capable of responding to the infection in at least five different ways. In
      addition to exhibiting a local lesion at the site of reinoculation, accompanied
      by dissemination of the virus, they may show no local lesion at all but present
      evidence of dissemination of the virus together with the development of a
      positive Wassermann reaction. In some instances the virus may be recovered from
      the reinoculation site although no local lesion is produced there and no
      dissemination of the virus can be shown to take place. An occasional animal
      treated before the 69th day of the disease remains completely refractory to a
      second infection. When treatment is postponed to 6 months or more after the
      original inoculation, reinfection carried out by intratesticular injection is
      almost always impossible and such animals appear to be entirely refractory.
      However, if rabbits treated late are reinoculated with the homologous strain by
      depositing the virus upon a granulating wound on the back, successful
      reinfections can be accomplished in at least 50 per cent of the test animals. The
      resistance which develops in rabbits in the course of syphilitic infection is,
      then, not absolute but relative. It is pointed out that these results cast
      discredit upon the validity of the reinoculation method as a test of cure in
      syphilitic infection. It is also suggested upon the basis of these experiments,
      that the subsequent occurrence of a positive Wassermann reaction in patients with
      early syphilis in whom the Wassermann reaction has become negative under
      treatment may not always represent a relapse in the the disease but possibly in
      some instances a new infection without clinical signs.

PMID- 19869210
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : VI. ON THE VIRULENCE OF THE
      OVERGROWTH IN THE LYSED CULTURES OF BACILLUS PESTIS CAVIAE (M. T. II).
AB  - Resistants isolated from the overgrowth of cultures of B. pestis caviae (M. T.
      II) lysed by various strains of specific bacteriophage proved to be avirulent
      when administered to mice by feeding, or by intraperitoneal injection. These
      cultures remained resistant to the action of bacteriophage so long as they were
      carried on agar. When transferred to broth, however, one group of resistants,
      namely, those isolated by means of "weak" phages, became susceptible to lysis
      after five to seven daily passages. The other group of resistants, isolated from
      the cultures lysed by one of the "strong" phages, failed to become susceptible to
      lysis even after nearly 200 passages in broth. Simultaneously with the recovery
      of susceptibility, the cultures of the first group regained a degree of virulence
      comparable to that of the parent culture of B. pestis caviae. The cultures of the
      second group of resistants have failed thus far to recover virulence (10 months
      after isolation). The latter cultures, apart from lack of both virulence and
      susceptibility to lysis, are identical with the parent culture of B. pestis
      caviae, as indicated by biochemical and antigenic properties. Our findings offer
      evidence in favor of the view that resistant strains result from selection among
      variants already existing in the parent culture and do not arise through the
      inheritance of specific immunity properties produced by the action of phage.

PMID- 19869211
TI  - THE SURVIVAL OF THE TUBERCLE BACILLUS IN SUSPENSION IN PHYSIOLOGICAL SALT
      SOLUTION.
AB  - Three suspensions of tubercle bacilli in physiological salt solution were still
      virulent for guinea pigs after 310, 325, and 330 days at refrigerator
      temperature. One of these cultures on which recent tests had been made had lost
      very little, if any, of its virulence for guinea pigs in 325 days.

PMID- 19869212
TI  - THE BEHAVIOR IN VIVO OF CERTAIN RELATIVELY PURE ANTIGENS.
AB  - The experiments are of interest in several respects. It is clear that
      crystallized egg albumen is rapidly eliminated from the circulation and in the
      experiments cited it could no longer be detected after 18 or 19 hours. A
      considerable portion of it rapidly passes through the kidney in an apparently
      unaltered state. Evidently this passage begins almost at once and may continue
      for a day or two. In an experiment not reported in this paper, egg albumen
      appeared in naturally voided urine 2 hours following its injection into the
      peritoneal cavity. In the experiments reported no urine was voided until 5(1/2)
      and 6(1/2) hours following intravenous administration, but in each instance egg
      albumen was present in considerable amounts. However, sufficient egg albumen must
      have been utilized to produce antibody. It is hardly to be expected that such a
      protein, whose elimination is so rapid, could persist unaltered within the body
      and reappear within the circulation coincident with its antibody. The behavior of
      the protein cannot be ascribed to alterations which may have taken place during
      the process of crystallization since Ascoli showed that the proteins of egg white
      readily pass from the circulation into the urine. Certain observations of the
      writer confirm this point. The experience of Alexander, Becke, and Holmes who
      exposed sensitized guinea pigs to sprays of dilute egg white with the result that
      80 per cent of the animals developed symptoms of anaphylaxis, further strengthens
      the contention that certain of the membranes are readily permeable for the
      proteins of egg. The conditions following the injection of casein are different.
      There is no appreciable passage through the kidney. Casein is present within the
      circulation for a considerable period; it could be detected in the blood serum 12
      and 13 days after its introduction into the peritoneal cavity. Antibody appeared
      on the 7th and 8th days, respectively, so that both antigen and antibody were
      present in the serum for a period of 3 or 4 days. The phenomenon of antigen and
      antibody occurring together might be explained on the ground that certain
      proteins are utilized slowly and that the antibody found in the blood, usually
      after the 7th day, results from the portion of antigen first utilized. During the
      next few days a continual supply of antibody enters the circulation and during
      the period there is a steady utilization of the antigenic substance; it is
      possible that during this time there is constant union of antigen and antibody
      within the blood, with the slow utilization of the antigen and a slight
      utilization of the antibody which is made up by a slow increase from the body
      cells. Thus there would be a period in which considerable antigen would be
      present with weak antibody, succeeded by a second period when the amount of
      antigen would be small with well defined antibody, and finally only antibody.
      Certain observations tend to support such a view. Bayne-Jones injected rabbits
      whose serum contained precipitin from egg albumen with this substance and noted
      the occurrence of both antigen and antibody for a period of 48 hours. Some of his
      experiments in vitro are equally suggestive. In one instance a rabbit well
      immunized with egg albumen was injected intravenously with this substance. An
      hour later it was bled and the stored serum refrigerated for a period. During
      this time there was a slow spontaneous precipitation with a decline in both
      precipitin and antigen titer, but even after 6 days both were present. After a
      longer period only antigen remained. P. A. Lewis and D. Loomis have shown that an
      injection of sheep red blood cells in guinea pigs results in a well defined
      hemolysin titer about the 9th day, followed by a definite decline, with a
      secondary rise in hemolysin until the peak is reached on the 20th day. It becomes
      evident, then, that the reaction of the rabbit to a single injection of a
      relatively pure protein will depend on the character of the protein injected.
      When crystallized egg albumen is administered it is rapidly eliminated from the
      circulation. The rapid disappearance of the egg albumen from the blood stream is
      partly accounted for by its prompt elimination through the urine. Antibody
      appears in the serum from the 7th to the 10th day. Casein behaves differently. It
      persists in the blood for a considerable period; after the 7th or 8th day both
      antigen and antibody may be demonstrated in the blood. Casein cannot be detected
      in the urine following its injection into the body. The behavior of casein within
      the body affords an analogy with the conditions frequently noted after the
      administration of foreign serum, in both cases both antigen and antibody may be
      present in the circulation together.

PMID- 19869213
TI  - THE RELATION BETWEEN BODY AND ORGAN WEIGHTS IN THE RABBIT.
AB  - Data from 645 normal rabbits were used as the basis of an investigation of the
      relation existing between body and organ weights. Actual and relative weights
      were correlated with both gross and net body weight. The results obtained varied
      with different classes of organs but it was found that, in general, there was an
      agreement between the form and degree of the correlation shown and the structural
      and functional properties of the organs concerned.

PMID- 19869214
TI  - THE OCCURRENCE AND TREND OF SPONTANEOUS VARIATIONS IN ORGAN WEIGHTS OF NORMAL
      RABBITS.
AB  - Records of organ weights of normal rabbits covering a period of 3(1/2) years were
      analyzed with a view to determining first, whether any significant variations of
      an orderly character could be demonstrated and, second, the general trend of the
      variations that occurred. It was found that many organs showed decided variations
      in weight which assumed the form of definite annual cycles. In addition, there
      was some evidence of a second cycle covering a period of years. These changes
      were most marked in the case of the endocrine glands (including the testicles),
      the lymphoid organs, and the liver.

PMID- 19869215
TI  - STUDIES IN AGGLUTINATION : III. ON THE MECHANISM OF THE AGGLUTINATION OF BACTERIA
      BY SPECIFIC AGGLUTINATING SERUM.
AB  - FROM THE FOREGOING EVIDENCE, SPECIFIC BACTERIAL AGGLUTINATION MAY BE CONCEIVED OF
      AS FOLLOWS: When bacteria are mixed with their homologous agglutinative sera,
      specific union between organism and agglutinin occurs. This interaction consists
      of specific coating of the bacteria by globulin. By virtue of the fact, noted by
      Loeb and illustrated in Fig. 6, that protein film formation gives the coated
      particle the characteristics of denatured protein, the bacteria now take on the
      character of particles of denatured globulin. Particles of denatured protein
      flocculate whenever their charge is reduced by electrolyte to a critical level
      lying somewhere between 12 and 14 millivolts. This is true even when the salt is
      strong, as, unlike bacterial particles, their cohesive force is not readily
      depressed by salt. The sensitized bacteria, now being essentially particles of
      denatured protein, likewise agglutinate as soon as their charge is reduced by
      electrolyte to this potential level.

PMID- 19869216
TI  - IMMUNOLOGICAL RELATIONSHIPS OF ENCAPSULATED AND CAPSULE-FREE STRAINS OF
      ENCAPSULATUS PNEUMONIAE (FRIEDLANDER'S BACILLUS).
AB  - 1. "S" strains of Friedlander's bacillus produce capsules, soluble specific
      substance, and are of exalted virulence. "S" strains are type-specific and react
      with only the type-specific antibodies of the homologous types. 2. Immunization
      with "S" cells induces the formation of antibodies which agglutinate type
      specifically, precipitate the corresponding soluble specific substance, and
      protect white mice against infection caused by organisms of the same type. 3. "R"
      strains of Friedlander's bacillus produce no capsules, produce no soluble
      specific substance, and are not pathogenic. "R" strains are serologically
      undifferentiated from each other and react with only the species antibodies. 4.
      Immunization with "R" cells induces antibodies which do not agglutinate
      encapsulated organisms, do not precipitate soluble specific substance, and do not
      afford protection against infection by Friedlander's bacillus. Anti-R serum
      contains only the species antibody which reacts with any capsule-free organism
      regardless of its type origin. 5. Decapsulation of "S" cells by heat and acid
      chemically converts a type-reacting organism into a species-reacting organism.

PMID- 19869217
TI  - ETIOLOGY OF OROYA FEVER : III. THE BEHAVIOR OF BARTONELLA BACILLIFORMIS IN
      MACACUS RHESUS.
AB  - The experiments reported here were carried on in the main with passage strains of
      Bartonella bacilliformis, and the results indicate that the virulence of the
      organism has been considerably enhanced by passage through susceptible animals.
      While the animals of the earlier experimental series showed no anemia, some of
      the present group manifested a definite reduction in the number of red cells and
      in hemoglobin, and in one instance (M. rhesus 25) anemia was of the extreme type
      so often associated with Oroya fever in man. The anemic condition appeared to be
      secondary in character, however, nucleated red cells being few in number. In this
      animal also Bartonella bacilliformis was readily demonstrated in the erythrocytes
      by means of stained smears, though the number of cells invaded by the parasites
      was by no means so great as in the human infection. In most instances of
      experimental Bartonella infection so far induced the demonstration of the
      parasites by ordinary routine examination of stained film preparations is
      possible only when the titer of the blood exceeds 1:1,000. Prolonged search of
      many slides has not been attempted, however. The number of microorganisms in the
      blood, as shown by culture tests of ascending dilutions, was in most instances
      highest (1:100,000 to 1:10,000,000) during the early period of the infection
      coincident usually with the period of highest fever, falling to a titer of 1:10
      during the last half of the disease. In one of the fatally infected monkeys,
      however, the titer increased from 1:10 on the 4th day to 1:1,000,000 on the 24th
      day. The titer of the blood was equally great in Monkeys 5 and 6, although the
      former was inoculated locally, the other intravenously and intraperitoneally. The
      largest proportion of infected red cells was found in Monkey 25, while the blood
      titer, as shown by culture test, was highest in Monkey 7. The febrile reaction
      varied in the animals of this series from a severe continuous fever of 104-105
      degrees F., lasting 2 to 3 months, in one instance, with a remittence during the
      3rd to 5th weeks, to the acute high fever (106 degrees F.) of 1 day's duration in
      the fatally infected monkey, No. 25. The more usual reaction, however, is an
      irregular course of moderate fever with one or more periods of high temperature
      (105 degrees ). Bartonella bacilliformis was constantly demonstrated, both
      microscopically and by culture tests, in the lymph glands of animals sacrificed 2
      to 3 months after inoculation, and in two of three instances it was present also
      in the spleen, bone marrow, and heart blood. In the case of M. rhesus 6, which
      died 26 days after inoculation, the microorganism was obtained also in culture
      from the lymph glands, spleen, and heart blood taken at autopsy. In the other
      animal which died, a terminal bactelial infection, while not obscuring the
      effects of the Bartonella infection, made it impossible to isolate the parasite
      from either blood or tissues. The skin lesions, whether of the nodular type,
      induced by introduction of the virus intradermally or by application to the
      scarified skin, or of the miliary character occurring spontaneously as a result
      of systemic infection, always yielded cultures of Bartonella bacilliformis, and
      stained sections of such lesions revealed the parasites in large numbers in their
      characteristic situation in the endothelial cells. A chronic, systemic infection,
      in which the lymph glands are enlarged and Bartonella bacilliformis is present in
      the blood in high titer, may be induced by local inoculation, as shown in the
      case of M. rhesus 5. The local lesions induced in one instance by introduction of
      a passage strain, both intradermally and by scarification, attained within 2
      months extraordinary size, the nodules arising at adjacent sites of inoculation
      on the right eyebrow having coalesced into a large pedunculated mass which
      overhung the eye. This type of reaction had not been observed hitherto in the
      course of the present study but has been described by earlier investigators as a
      result of the inoculation of monkeys with human verruga tissues. The striking
      fact brought out in the present study is the variety of responses to inoculation
      which animals of the same species may manifest. The clinical features of the
      infection may be typical of Oroya fever or may resemble those of verruga
      peruviana, and in M. rhesus 25 we have an instance of a type of infection in
      which the characteristic phenomena of both conditions are simultaneously present.
      Whether the appearance will resemble those of the one or the other condition
      appears to depend on the susceptibility of the individual as well as on the
      virulence of the organism. Moreover, it seems probable that different degrees of
      resistance to the invasion of the parasite on the part of the blood cells,
      internal organs, or skin of a given animal may determine the predominant clinical
      manifestations of the infection. The factor of variation in susceptibility of
      different individuals or different tissues of the same individual would account
      for the variety of types of human Bartonella infection.

PMID- 19869218
TI  - ETIOLOGY OF OROYA FEVER : IV. THE EFFECT OF INOCULATION OF ANTHROPOID APES WITH
      BARTONELLA BACILLIFORMIS.
AB  - The inoculation of a chimpanzee with cultures and a passage strain of Bartonella
      bacilliformis induced local reactions which, while definite and characteristic,
      progressed less rapidly and were much less striking than those in the control
      rhesus monkey. Bartonella bacilliformis was demonstrated in the blood corpuscles
      with difficulty, and the fever was slight compared with the high and persistent
      fever of the rhesus monkey. In both the swelling of the lymph glands was an early
      symptom and constantly present. Definite anemia developed in the chimpanzee only
      after accidental infection with Rocky Mountain spotted fever and may have been
      due to either one or both infections, though it disappeared when the blood had
      become negative by culture for Bartonella bacilliformis and the local lesions had
      disappeared. Incidentally, the chimpanzee was found in this one instance to be
      less susceptible to the spotted fever than Macacus rhesus and guinea pigs. In the
      ourang-utan, also, Bartonella bacilliformis induced a mild systemic and local
      infection. A rise of temperature occurred 10 days after inoculation) and fever
      continued for a week, though it was decidedly less severe than that in the
      control rhesus. The lesions induced by scarification were less definite than
      those which arose at the sites of intradermal inoculation. Bartonella
      bacilliformis was recovered from the blood on the 9th and on the 16th days after
      inoculation and from nodules excised on the 33rd and 53rd days. A few
      erythrocytes containing the organism were demonstrated in stained smears, but
      prolonged search was required to find them. The symptoms and lesions observed in
      the chimpanzee and ourangutan as a result of infection with Bartonella
      bacilliformis are far milder than those of rhesus monkeys and show less
      resemblance to human Oroya fever or verruga.

PMID- 19869219
TI  - ETIOLOGY OF OROYA FEVER : V. THE EXPERIMENTAL TRANSMISSION OF BARTONELLA
      BACILLIFORMIS BY TICKS (DERMACENTOR ANDERSONI).
AB  - Experiments are reported in which Bartonella bacilliformis was transmitted from
      infected to normal rhesus monkeys by the bite of the tick, Dermacentor andersoni.
      A long period of feeding, both on the infected animal and on the normal animal
      subjected to infection, was required in order to secure positive results. The
      infection transmitted by the ticks was mild, but definite, as shown by the
      recovery of Bartonella bacilliformis from the lymph nodes and blood.

PMID- 19869220
TI  - IMMUNOLOGICAL RELATIONSHIPS OF CELL CONSTITUENTS OF ENCAPSULATUS PNEUMONIAE
      (FRIEDLANDER'S BACILLUS).
AB  - 1. The soluble specific substance of Friedlander's bacillus is non-antigenic when
      dissociated from the cell. It is different for each type and it is highly
      reactive in the corresponding anti-S serum. 2. The nucleoprotein is antigenic,
      induces the species or protein antibody which reacts with capsule-free cells and
      protein derived from all types. Antiprotein sera do not react with either the
      encapsulated cell or the polysaccharide derived from it, and they offer no
      protection against infection. 3. Anti-R and antiprotein sera are identical in
      their behavior. 4. The carbohydrate of Friedlander's bacillus is demonstrable in
      filtrates of actively growing cultures and in the blood and urine of infected
      animals. 5. The protein is demonstrable in filtrates of only old, disintegrating
      cultures.

PMID- 19869221
TI  - AN EXPERIMENTAL ANALYSIS OF BACTERIAL ALLERGY.
AB  - Our experiments have confirmed the fact that the so called bacterial allergies
      are dependent upon a mechanism which differs materially from that determining
      true protein anaphylaxis. Anaphylaxis to protein substances of the bacteria
      probably occurs but plays a relatively unimportant role in the phenomena of
      infection. The bacterial allergies, however, are of great importance since they
      develop rapidly and render the infected animal highly vulnerable to products of
      the bacterial growth which are relatively innocuous for the normal animal.
      Neither the type-specific carbohydrate "residue antigens" (the "soluble specific
      substances" of Avery and Heidelberger) nor the antibodies reacting with them play
      any part whatever in bacterial allergy, and since these type-specific substances
      represent the haptophore groups of the whole bacteria by which they react with
      the agglutinins, precipitins, sensitizers, etc., of immune serum, allergy, as
      previously determined by Mackenzie and Woo, is in no way related to that phase of
      resistance which is determined by these antibodies. This does not, however,
      preclude the possibility that allergic hypersusceptibility may not in some way be
      related to other factors of resistance more definitely associated with cellular
      rather than with intravascular reactions. Our previous studies with Jennings and
      Ward in tuberculosis point in this direction (20). Guinea pigs can be actively
      sensitized with all the bacteria with which we have worked when repeated
      injections of whole bacteria or of the protein (nucleoprotein) fraction are
      administered. Large amounts of the latter are necessary since these materials are
      indifferent antigens, possibly because of the severe manipulations necessary in
      their production. Sensitiveness develops usually within 10 days after the first
      dose and increases with continued treatment for 3 or 4 weeks. Sensitiveness is
      relatively specific, by which we mean that there is a definite specificity which,
      however, in highly sensitive animals is not absolute and shows considerable
      overlapping. Continued treatment with considerable quantities of the above
      substances leads to gradual desensitization in animals in which there are no
      chronic foci present, which, as in tuberculosis, tends to continue the
      sensitization. Attempts at passive sensitization have been irregular and
      inconclusive. When any degree of sensitiveness has developed after the injection
      of immune sera, it has appeared late and has been of doubtful specificity.
      Conversely we have failed in any case to neutralize the activity of the active
      allergic constituents of bacterial extracts by incubation with any type of immune
      serum. We have failed so far to show any increased fixation of tuberculin
      material on the part of tuberculous tissues or on that of living tuberculous
      animals. These failures, however, seem to us of relatively slight importance
      since quantitative experiments of this nature are extremely difficult in the case
      of a substance as delicately potent for the tuberculous animal. On the other hand
      we have obtained definite, though irregular evidence that the incubation of O.T.
      with fragments of tuberculous lung tissue (less clearly with other tissues) leads
      to the formation of a substance that produces allergy-like lesions in the skin of
      normal guinea pigs. With somewhat greater regularity, similar treatment of O.T.
      has enhanced the potency of the tuberculin for tuberculous animals. And, in these
      experiments there was evidence that the factor responsible for this action was
      not easily separable from the cells themselves. When these experimental data are
      analytically considered they appear in many respects confusing and contradictory.
      There has been so much work done on the tuberculin reaction, moreover, that, in
      the face of experimental inconsistencies it would seem foolhardy to formulate
      more than tentative suggestions to explain the mechanism of these reactions.
      Nevertheless there are a few outstanding and sufficiently reliable facts which
      compel a limited number of definite deductions. In the first place there is no
      question of the complete independence of the true allergic phenomena from the
      ordinary bacterial antigen-antibody reactions. We know, moreover, that the
      allergic substance is chemically separable from the carbohydrate "residue" or
      haptophore group of the bacteria (Mueller, Laidlaw and Dudley). Indeed it has
      been shown by Long and Seibert (21) that the active allergic substance is either
      a protein in itself, or at any rate closely associated with the bacterial
      protein. Furthermore, the distinct, though limited, specificity of the allergic
      sensitiveness compels the conclusion that we are dealing with an immunological
      process in which the tissue cells acquire an increased specific capacity to react
      with this nitrogenous material, a capacity which, in principle, is not far
      removed from the supposed "sessile receptor" apparatus which is conventionally
      held responsible for protein anaphylaxis; and this analogy is further amplified
      by the apparent desensitization which continued treatment produced in many of our
      own experiments as well as in those of Mackenzie and Woo. Here, however, the
      analogy with protein anaphylaxis ends. Passive sensitization with any form of
      immune serum or with the sera of highly sensitized animals is either feeble or
      entirely unsuccessful and indicates quite convincingly that, whatever the
      receptor apparatus of the cells may be, it is not easily given up to the blood
      stream as are ordinary antibodies. Further than this, our tissue-tuberculin
      experiments, irregular and occasional as they were, nevertheless convinced us
      that: 1. The contact with the tissues of tuberculous animals results in the
      production of a toxic factor, not unlike the autolytic toxic materials of some
      bacteria. 2. The active cell constituent by which this action is wrought, is not
      easily separated from the cells, even by energetic methods of extraction. This
      close association of the entire process with the cells themselves is particularly
      significant in view of the obvious cell injury in which these delayed allergic
      effects differ from the ordinary urticarial, evanescent reactions associated with
      protein anaphylaxis. The process of allergy, as far as we can approach it then,
      may be conceived as follows: A nitrogenous, probably protein, constituent of the
      bacterial growth or of its body substance stimulates a specific reaction in the
      tissue cell by which its specific capacity to establish contact with this
      constituent is enhanced. The cell is thereby enabled to exert a, probably, enzyme
      like effect upon this material in consequence of which a toxic substance is
      liberated, largely upon or possibly within the cell itself. Both processes may be
      dependent upon one and the same reaction body. But it seems more likely that
      increased contact and the increased cell activity are separately developed, an
      assumption which is rendered probable by the association of the highest degrees
      of allergy with inflammatory cell reactions, and by the fact that moderate and
      less specific allergic sensitiveness follows 10 or more days after the
      administration of considerable amounts of indifferent protein substances to
      guinea pigs. We interpret this as signifying that such injections may non
      speciffcally increase cellular activity, a change which many earlier workers have
      spoken of as "cell irritability." Both processes are closely associated with the
      altered cell itself and the factors by which the reaction is brought about are
      not easily given up to the blood stream as are the antibodies formed in response
      to injections of proteins or whole bacteria. We are confronted, therefore, with
      an immunological mechanism which has some close analogies to those others in
      which circulating antibodies are formed, but which differs from these mainly in
      the intimacy with which the entire reacting system is associated with the cells
      themselves. It is difficult to conceive that a functional cell alteration, as
      profound as this, should be entirely unrelated to the phenomena of susceptibility
      or resistance.

PMID- 19869222
TI  - TISSUE-DIGESTING ENZYME (HISTASE) OF STREPTOCOCCI.
AB  - 1. An extracellular, proteolytic enzyme has been observed in more than 30 strains
      of beta type, aerobic and facultative hemolytic streptococci. 2. The enzyme is
      readily demonstrable in sterile filtrates of cooked meat cultures. 3. No gas or
      foul odor is produced. 4. It is partially inactivated by exposure to about 60
      degrees C. for 45 minutes or longer. 5. The enzyme manifests itself in cooked
      meat cultures after about 48 hours incubation at 37 degrees C. The sterile
      filtrate from a 10 day old culture acts within 18 hours. 6. From 50 to 75 per
      cent of the meat in a tube of cooked meat medium may be digested in about 3 weeks
      at room temperature after 5 days initial growth at 37 degrees C. 7. No
      correlation is found, in the cases studied, between hemolysis and proteolysis. 8.
      Streptococci not digesting beef tissue will not digest human tissue, and those
      which do digest beef tissue also digest human tissue. This conclusion applies
      only to the nine strains studied. 9. Ability to digest animal tissues does not
      necessarily imply ability to digest casein, coagulated beef serum or gelatin. 10.
      The disappearance of the meat from cooked meat cultures of hemolytic streptococci
      is quantitatively roughly paralleled by increase of formol-titrable substances in
      the fluid portion of the medium. 11. The enzyme resembles trypsin in its action.
      Streptococci from a variety of sources, bovine, human and otherwise have shown
      varying degrees of proteolytic activity. 12. The name histase is proposed for
      this enzyme.

PMID- 19869223
TI  - BACTERIUM PNEUMOSINTES IN CLINICAL INFLUENZA IN NEW YORK CITY IN 1926.
AB  - The presence of Bacterium pneumosintes has been demonstrated in nasopharyngeal
      washings from 2 patients in a sporadic outbreak of clinical influenza in New York
      City in March, 1926. 2 strains of bacteria morphologically similar to Bact.
      pneumosintes, but differing in certain cultural characters, and 2 other anaerobic
      filter-passing organisms were also isolated from the 9 patients examined. The
      blood serum of 16 among 17 persons convalescent from clinical influenza, and of 6
      among 10 supposedly normal persons, agglutinated 1 or more strains of Bact.
      pneumosintes.

PMID- 19869224
TI  - EXPERIMENTAL HIGH JEJUNOSTOMY IN THE DOG, WITH BLOOD CHEMICAL STUDIES.
AB  - 1. The effect of high jejunostomy upon the life and chemical changes of the blood
      of dogs is here reported. 2. Sodium chloride solution administered in sufficient
      quantity after high jejunostomy prolongs the life of dogs. 3. Such experimental
      findings as these warrant a careful cinical study of the effects of high
      jejunostomy so frequently used in the treatment of acute intestinal obstruction.

PMID- 19869225
TI  - STUDIES ON THE ETIOLOGY OF HEARTWATER : III. THE MULTIPLICATION OF RICKETTSIA
      RUMINANTIUM WITHIN THE ENDOTHELIAL CELLS OF INFECTED ANIMALS AND THEIR DISCHARGE
      INTO THE CIRCULATION.
AB  - The Rickettsiae of heartwater are more definitely restricted to the vascular
      endothelial cells of infected animals than are those of typhus or Rocky Mountain
      spotted fever. They likewise form more pronounced spherical colonies within the
      cells. Their presence does not injure the endothelial cells to a degree at all
      comparable with that caused by the other pathogenic Rickettsiae. The rupture of
      endothelial cells and discharge of Rickettsiae, which are apparently viable, into
      the circulation constitute phenomena not thus far reported in the case of typhus
      or Rocky Mountain spotted fever.

PMID- 19869226
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : VI. FACTORS DETERMINING
      THE REACTION OF SKIN GRAFTS; A STUDY BY THE INDICATOR METHOD OF CONDITIONS WITHIN
      AN ISCHEMIC TISSUE.
AB  - By means of vital staining with indicators a study has been made of the changes
      in reaction and in certain other attributes of a tissue abruptly rendered
      ischemic. Grafts of mouse skin have been employed as test material. It has been
      found that almost at once after implantation vigorous grafts become notably acid
      as compared with the normal skin and that they survive and "take" despite the
      acid condition, which remains at a maximum for several days. Weak or injured
      grafts on the contrary tend to be as alkaline as their surroundings, if not more
      so. Through experiments directed to the purpose reasons for this difference have
      been found in the lessened metabolic activities of the cells of the injured skin,
      and in an increased permeability which leads to a generalized suffusion of the
      damaged tissue with the alkaline lymph and an abnormally rapid escape of carbon
      dioxide from it. The influence of these factors to determine the reaction of
      tissues dying within the body has not been sufficiently taken into account in
      considering the chemical changes that occur after cell death, and some revision
      of current views regarding these as they affect small necrotic masses would seem
      called for. Carbon dioxide penetrates so readily into the living skin as to cause
      some local increase in the hydrogen ion concentration within cutaneous regions
      exposed to an atmosphere of it, even when the local circulation and the
      ventilation by way of the lungs have not been interfered with. It penetrates
      injured skin with especially great ease. Tissue acidosis and edema not
      infrequently occur together; but no relationship between them of cause and effect
      has been made out.

PMID- 19869227
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : VII. THE INFLUENCE OF
      CHANGES IN THE REACTION OF THE BLOOD UPON THE REACTION OF THE TISSUES.
AB  - The introduction into the blood stream of dilute hydrochloric acid or sodium
      carbonate in quantities not too great to be compatible with life results in
      marked alterations in the color of certain of the matrix tissues stainable in
      vivo with phthalein indicators. Connective tissue in its various forms, and
      tendon and cartilage all become relatively more acid or alkaline than the normal.
      The hue of the kidney cortex also changes, as might be expected from its
      functions. The pancreas and lymph nodes, on the other hand, appear unaffected
      even when the injection is pushed to the extreme; and the slight to negligible
      alterations in the hue of the liver may be due to changes in the color of the
      associated secretion. The matrix tissues just mentioned behave as if unable to
      maintain a reaction of their own; whereas the elements of the parenchymal organs
      would seem to make their own conditions even when so much acid or alkali has been
      injected as will lead to death of the animal. Injections of lactic acid are well
      tolerated and it is difficult to bring about alterations in the color of the
      phthalein-stained matrix tissues by means of them. Salt solution, and sugar in
      large amount cause no changes in color such as would indicate changes in
      reaction. The results with the various phthalein indicators are in close accord,
      attesting that the information these give under vital conditions is reliable.

PMID- 19869228
TI  - A FILTERABLE VIRUS PRESENT IN THE SUBMAXILLARY GLANDS OF GUINEA PIGS.
AB  - In the lesions of herpes simplex and similar conditions due to filterable
      viruses, cells are present which show characteristic alterations, particularly in
      the nucleus. The nucleus of these cells contains a mass which stains with acid
      dyes. Surrounding this mass is a clear space or halo, within which there are
      large granules staining with basic stains. These cells are little if at all
      enlarged. In a few human cases, especially in infants, enlarged cells have been
      found which contain nuclei showing changes similar to those seen in the abnormal
      cells of herpes simplex. In the ducts of the submaxillary glands of guinea pigs,
      Jackson observed structures which she considered to be protozoan parasites. Our
      own studies indicate, however, that these structures are greatly swollen
      epithelial cells with nuclei having the same characters as the nuclei of the
      atypical cells in the lesions of herpes simplex. These cells are usually
      surrounded by a mononuclear cellular reaction. They were found in 84 per cent of
      the full grown guinea pigs examined but they were present in only three of forty
      three young guinea pigs less than 1 month old. The resemblance of these cells,
      except as regards size, to the atypical cells present in lesions due to
      filterable viruses suggested that they also may be the result of an infection
      with a similar agent. That they are usually not present in guinea pigs less than
      1 month old indicates that natural infection usually occurs after this period.
      Experiments were therefore undertaken to determine whether or not an infective
      agent is concerned in this condition and if so to learn something of its nature.
      When an emulsion of the submaxillary glands of full grown guinea pigs is injected
      into the brains of young guinea pigs the animals have fever and exhibit symptoms
      of cerebral irritation. They usually die in 5 to 7 days and in sections of the
      brain a diffuse subacute meningitis is found. In the exudate there are large
      numbers of cells having all the characteristics of the abnormal cells of herpes
      simplex. Similar cells are present in the lesions resulting from the injection of
      the same emulsion into the testicle, lung, tongue, and submaxillary glands of
      young guinea pigs. In none of these lesions, however, are the cells greatly
      enlarged as they are in the lesions in old guinea pigs. These results support the
      view that the lesion in the submaxillary gland of old guinea pigs is due to an
      infective agent. Attempts were therefore made to transmit this agent through a
      series of young guinea pigs. When the injections were all made into the same
      organ all the experiments but one gave negative results, but when the site of
      injection was changed at each transfer it was possible in a number of instances
      to reproduce the lesions through two animals in series and in one experiment
      through three animals in series. By modifying the technique, efforts were made to
      transmit the infection indefinitely but these attempts were unsuccessful. No
      explanation can be offered for this failure. Studies made to determine some of
      the properties of the infective agent have shown that it is destroyed by heating
      at 54 degrees for 1 hour, and that it is not injured by preservation in 50 per
      cent glycerol for as long as 11 days. After the material had remained in 50 per
      cent glycerol for 28 days, however, it was found to be no longer infective. The
      infective agent was not held back by a Berkefeld N filter which was impermeable
      to bacteria. It seems probable therefore that the infective agent belongs in the
      group of filterable viruses, though further work will be necessary to learn more
      of its exact nature. These observations present additional evidence that the
      presence of cells with nuclear inclusions in any lesion indicates that the injury
      is probably due to an infective agent belonging in the group of filterable
      viruses.

PMID- 19869229
TI  - STUDIES CONCERNING THE RELATIONSHIP BETWEEN PNEUMOCOCCI AND STREPTOCOCCI.
AB  - Morgenroth and his collaborators grew pneumococci in a medium containing optochin
      and derived variant forms of bacteria therefrom which were considered to be
      streptococci of the viridans group. We have repeated these experiments and have
      also derived variant forms. These atypical races, however, we have found to be
      identical with the R form of pneumococci which have been obtained by various
      other methods. That these R cultures are still pneumococci and do not belong in
      the Streptococcus viridans group is supported by the following observations: 1.
      These strains are not bile-insoluble, but are more resistant to the lytic action
      of this agent than are type-specific pneumococci. 2. R strains behave like
      pneumococci and not like streptococci in the readiness with which cultures
      spontaneously autolyze and saline suspensions disintegrate during freezing and
      thawing. 3. Immunological reactions of the variant pneumococci derived by
      Morgenroth's method are identical with the immunological reactions of R forms of
      pneumococci derived by various other means. The observations of Morgenroth and
      his associates in regard to the transformation of Streptococcus haemolyticus into
      Streptococcus viridans by treatment with rivanol could not be repeated in this
      laboratory. No explanation is at hand for our failure to produce the change. It
      is of course possible that none of the twenty-six strains tested had suitable
      tendencies to variation or that the technic or reagents employed varied from
      those of Morgenroth.

PMID- 19869230
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : V.
      PRODUCTION OF ANTIHEMOTOXIN BY IMMUNIZATION WITH OXIDIZED PNEUMOCOCCUS HEMOTOXIN.
AB  - Immunization with solutions of the intracellular substances of pneumococci, in
      which the hemotoxin has been rendered inactive by oxidation, yields an antibody
      which neutralizes the active or reduced hemotoxin.

PMID- 19869231
TI  - EFFECT OF REPEATED FREEZING (-185 degrees C.) AND THAWING ON COLON BACILLI, VIRUS
      III, VACCINE VIRUS, HERPES VIRUS, BACTERIOPHAGE, COMPLEMENT, AND TRYPSIN.
AB  - Colon bacilli, Virus III, vaccine virus, herpes virus, bacteriophage, complement,
      and trypsin are either killed or inactivated by repeated freezing (-185 degrees
      C.) and thawing. As might be expected, some of the agents are more resistant than
      others. Hence it may be concluded that destruction or inactivation of an active
      agent by repeated freezing (-185 degrees C.) and thawing is not proof that it was
      possessed of life.

PMID- 19869232
TI  - EXPERIMENTAL OBSERVATIONS ON IRRADIATED, NORMAL, AND PARTIALLY
      PARATHYROIDECTOMIZED RABBITS : I. THE EFFECTS OF PARTIAL PARATHYROIDECTOMY.
AB  - Previous irradiation of rabbits with ultra-violet light, with a consequent
      hypertrophy of the parathyroid glands, resulted in some degree of protection to
      these animals, when part of the parathyroid tissue was extirpated. This fact
      indicates that the remaining hyperplastic tissue was potentially active, and that
      the increased factor of safety represented by this condition of the remaining
      tissue resulted in less loss of blood calcium, a more rapid initiation of
      recovery, and an absence of the rise in the inorganic phosphorus of the blood
      serum which was a characteristic result of partial parathyroidectomy in normal
      rabbits. A fall in calcium in all the irradiated rabbits, without a corresponding
      rise in phosphorus, shows that the drop in calcium is the primary reaction, and a
      rise in phosphorus a secondary reaction following parathyroidectomy. But the
      relation of the rise in phosphorus to the development of tetany remains obscure.

PMID- 19869233
TI  - EXPERIMENTAL OBSERVATIONS ON IRRADIATED, NORMAL, AND PARTIALLY
      PARATHYROIDECTOMIZED RABBITS : II. THE EFFECTS OF INJECTIONS OF CALCIUM CHLORIDE
      OR OF DISODIUM HYDROGEN PHOSPHATE.
AB  - No significant differences were found in the reactions of irradiated, normal, or
      partially parathyroidectomized rabbits to injections of calcium chloride or
      disodium hydrogen phosphate. Intravenous injections of calcium chloride caused
      only a transient rise in blood calcium, which returned to its former level within
      a few hours. The upper level of blood calcium concentration is independent of
      parathyroid control. Subcutaneous injections of disodium hydrogen phosphate
      caused, in all three groups of rabbits, a similar depression of the blood calcium
      level. After large doses of the phosphate solution, all of the rabbits showed
      signs of acute tetany in which many of them died. Death or survival was not
      determined, apparently, by the absolute depression of blood calcium. The rabbits
      that died were those, in all three groups, in which a phosphorus retention
      carried the initial rise in serum phosphorus to even higher levels in the hours
      preceding death, and so changed the normal calcium-phosphorus ratio to a small
      fraction of its former value.

PMID- 19869234
TI  - EXPERIMENTAL OBSERVATIONS ON IRRADIATED, NORMAL, AND PARTIALLY
      PARATHYROIDECTOMIZED RABBITS : III. THE EFFECTS OF INANITION.
AB  - The experiments described in the three papers of this series were undertaken to
      determine if possible the significance of the parathyroid hypertrophy that has
      repeatedly been found in rabbits after exposure to ultra-violet light. The fact
      that the hypertrophy was not accompanied by a corresponding increase in blood
      calcium led us to infer that the upper level of blood calcium concentration is
      governed by factors independent of parathyroid control, and that the gland
      hypertrophy under the influence of ultra-violet light might represent a potential
      functional capacity, or increased factor of safety, to protect the calcium level
      under conditions of stress or emergency. Partial parathyroidectomy in irradiated
      rabbits, compared with the same operation in normal controls, resulted in a
      similar immediate drop in blood calcium; but a more rapid restoration of the
      calcium level in the irradiated rabbits indicated a more prompt and active
      response to the emergency on the part of the remaining glands. In the second
      group of experiments no significant differences were found in the reactions of
      irradiated, normal, or partially parathyroidectomized rabbits to injections of
      calcium chloride or of disodium hydrogen phosphate. All three groups of rabbits
      rapidly eliminated the excess calcium from the blood. Their reactions to large
      doses of sodium phosphate, given subcutaneously, appeared to be related to
      phosphate elimination or retention in the individual animals. Those in each group
      which had phosphate retention in the blood died in acute tetany. So also in the
      fasting experiments, reported in this paper, no distinctions could be drawn
      between normal, irradiated, and partially parathyroidectomized rabbits on the
      basis of their calcium and phosphorus metabolism. Blood calcium was reduced in a
      similar manner in all three groups of rabbits, and wide individual variations in
      serum phosphorus levels preclude significant deductions. But the irradiated
      rabbits suffered disproportionate losses of weight during the fasting period and
      four of five of them died during the course of the experiment. The deaths of
      these rabbits are attributed to this more rapid consumption of their own tissues
      and possibly also to suprarenal injury caused both by fasting and by exposure to
      ultra-violet light.

PMID- 19869235
TI  - STUDIES ON BACTERIAL ENZYMES : I. MENINGOCOCCUS MALTASE.
AB  - Meningococci possess an endocellular maltase enzyme. The splitting of maltose by
      this enzyme has been demonstrated by a biological method based upon the acid
      fermentation of glucose by bacteria which have little or no action upon maltose.

PMID- 19869236
TI  - STUDIES ON BACTERIAL ENZYMES : II. MENINGOCOCCUS PEPTONASE.
AB  - The meningococcus cell contains a peptonase enzyme which hydrolyzes the peptides
      and similar constituents of commercial "peptone." The activity of this enzyme is
      independent of the presence of the formed bacterial cell. The peptonase enzyme is
      more resistant to heat and to oxidation than is the maltase enzyme of the same
      bacteria.

PMID- 19869237
TI  - STUDIES ON BACTERIAL ENZYMES : III. PNEUMOCOCCUS MALTASE AND LACTASE.
AB  - Lactase and maltase are constituents of the pneumococcus cell.

PMID- 19869238
TI  - THE ETIOLOGY OF VERRUGA PERUANA.
AB  - A saline suspension of a subcutaneous nodule excised from a verruga patient, and
      kept in the refrigerator for 14 days, on inoculation into two young Macacus
      rhesus monkeys (Nos. 33 and 34) induced irregular febrile reactions and
      enlargement of the lymph glands, and in one instance a subcutaneous nodule arose,
      independently of direct inoculation, on the tail. A microorganism has been
      isolated from the blood of both animals, and from the experimental nodule, which
      in pathogenic properties and in cultural and morphological characteristics is
      indistinguishable from the strain of Bartonella bacilliformis isolated from a
      case of Oroya fever. The spontaneous skin lesion of Monkey 34 and the
      subcutaneous nodules induced by intradermal inoculation of cultures of the
      microorganism were histologically typical of experimental verruga lesions in
      monkeys and identical with the skin lesions induced in monkeys by Bartonella
      bacilliformis. The organism, like Bartonella bacilliformis, is an intracellular
      parasite, being found in the cytoplasm of the proliferating endothelial cells of
      the lesions and in the erythrocytes of the blood. The same variations in the
      manifestations of disease which have been noted in experimental infection with
      Bartmetta bacilliformis were observed in the experimental verruga infection. In
      the second passage (Monkey 41) the infection induced by local inoculation of
      cultures was severe both locally and constitutionally and was accompanied by
      marked anemia. The organisms were found in the red cells in large numbers. In the
      third passage the systemic infection was less severe, but the local lesions were
      more striking. Detection of the parasites in the blood is far more certain by the
      cultural method than by microscopic examination, the latter procedure being
      successful only in rather severe infections. The result of blood culture is
      therefore the decisive method in the final diagnosis of the disease. Preliminary
      serological study shows that the organism isolated in the present instance from
      the skin lesion of a verruga patient and that previously obtained from the blood
      of a case of Oroya fever belong to the same serological group. The data obtained
      justify the conclusion that verruga peruana is caused by Bartonella
      bacilliformis. They also definitely establish the fact that the inoculation of
      blood or sanguineous exudate from lesions of verruga peruana is capable of
      inducing in susceptible individuals a severe febrile systemic infection, such as
      that to which Carrion succumbed. The designation "Carrion's disease" is therefore
      the appropriate one for both forms of the infection. Bartonella bacilliformis may
      be regarded as a bacterium, since it has the essential features of that group of
      microorganisms.

PMID- 19869239
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : VIII. ON THE COURSE OF
      THE TISSUE ACIDOSIS SECONDARY TO BLOOD ACIDOSIS INDUCED WITH HYDROCHLORIC ACID.
AB  - The changes in blood reaction caused by the injection into a vein of a weak
      solution of hydrochloric acid are accompanied by extravascular changes of similar
      magnitude within the subcutaneous tissue. Under the conditions of prolonged
      general anesthesia with ether or urethane the circulation to this tissue is so
      interfered with that an "outlying acidosis" may develop in addition to the
      acidosis immediately consequent on the blood state. Even under the best of
      circumstances the extravascular acidosis induced with hydrochloric acid affects
      not merely the tissue fluid but the reaction of the tissue itself. Rabbits in
      which a widespread extravascular acidosis has been produced, together with a
      blood acidosis as severe as is compatible with life, remain in good condition
      during the relatively long period over which this state of affairs persists.
      There is at no time any sign of capillary dilatation, though the vessels are
      bathed in relatively add fluid, and none of shock. No edema develops in the
      acidotic tissues, and the animals void large amounts of urine. The tissue
      acidosis lessens pari passu with that of the blood.

PMID- 19869240
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : IX. ON THE TISSUE
      REACTION AS INFLUENCED BY INHALATIONS OF CO(2)AND BY OVERBREATHING.
AB  - Breathing an atmosphere that contains the normal amount of oxygen but a large
      excess of carbon dioxide results in a tissue acidosis as well as one of the
      blood. The extravascular changes in reaction take place with far greater speed
      than when acidosis is induced with hydrochloric acid, and they do not persist as
      in the case of this latter but swiftly disappear when the animal breathes
      ordinary air once again. The changes parallel closely in magnitude and time those
      occurring in the blood. The same matrix tissues are rendered acidotic is when
      hydrochloric acid is administered. The blood alkalosis that results from a
      blowing off of carbon dioxide is accompanied by an extravascular alkalosis. Under
      the circumstances of our experiments the connective tissue became more alkaline
      than ordinary but no change was noted in the cartilage, a fact to be explained by
      the slight degree of the alkalosis and its brief duration.

PMID- 19869241
TI  - THE QUANTITY OF CHOLESTEROL IN THE BLOOD SERUM OF THE GUINEA PIG AS AN INHERITED
      CHARACTER; ITS RELATION TO NATURAL RESISTANCE TO TUBERCULOSIS, AND TO
      TUBERCULOSIS INFECTION.
AB  - 1. Infection with tubercle bacilli of bovine type produced no alteration in the
      serum cholesterol content in guinea pigs. 2. Certain controlled variations in
      diet produced no changes in the serum cholesterol content in guinea pigs. 3.
      Inbred families of guinea pigs known to manifest differing resistances to
      tuberculosis gave differing serum cholesterol values, but no direct relationship
      between the two sets of phenomena could be established. 4. It seems probable that
      in the guinea pig the cholesterol content of the blood serum is influenced by
      inherited factors.

PMID- 19869242
TI  - STUDIES IN BLOOD COAGULATION : I. CERTAIN CHARACTERISTICS OF COAGULATION AND
      THEIR MEASUREMENT.
AB  - The gross phenomena of normal blood coagulation have been studied for the purpose
      of obtaining methods for estimating certain characteristics of coagulation in
      connection with a malignant tumor of the rabbit. The technique is described for
      the estimation of clot formation rate and of clot retraction rate and extent. The
      range of normal and abnormal values secured by these procedures is given.

PMID- 19869243
TI  - STUDIES IN BLOOD COAGULATION : II. BLOOD COAGULABILITY IN MALIGNANT TUMOR AND
      OTHER DISEASES OF THE RABBIT.
AB  - Description is given of changes in blood coagulability found in diseases of the
      rabbit, including malignant tumor, spontaneous infections, non-bacterial diseases
      and lesions, and hemorrhagic states specifically induced. The changes involved
      variously the time of onset of blood coagulation, clot formation rate and the
      rate and extent of clot retraction.

PMID- 19869244
TI  - A METHOD FOR REPEATEDLY SAMPLING THE BLOOD OF THE PORTAL VEIN IN HEALTHY ANIMALS.
AB  - A method is described for repeatedly sampling the blood of the portal vein in
      healthy animals. The method has been employed in thirteen dogs with success in
      eight.

PMID- 19869245
TI  - ON THE ABSORPTION OF BILE PIGMENTS FROM THE INTESTINE.
AB  - Bilirubin as such is not reabsorbed from the intestine by way of the portal vein
      in healthy animals. Bilirubin may be absorbed from the intestine by the
      lymphatics but only in minute amounts. Urobilin is reabsorbed from the intestine
      by way of the portal vein and by way of the lymphatics.

PMID- 19869246
TI  - SOME OBSERVATIONS ON THE LYMPH AND BLOOD VESSELS OF THE RABBIT TRACHEA : WITH
      PARTICULAR REFERENCE TO THEIR ROLE IN THE PATHOGENESIS OF EXPERIMENTAL LOBAR
      PNEUMONIA.
AB  - 1. Winternitz, Smith, and Robinson have offered as experimental evidence in
      support of the lymphatic path of infection in lobar pneumonia, a series of
      injection experiments of the rabbit's tracheal submucosa. What these
      investigators supposed to be lymphatics are shown by us to be an unusual type of
      venous supply consisting of short, wide, and richly anastomosing vascular
      channels. 2. There is little homology between the structure and distribution of
      the lymph and blood vessels in the human and rabbit trachea. 3. Injections of
      pneumococci by the tracheal route to produce lobar pneumonia in the rabbit
      include an intravenous administration of these organisms when the mucosa is
      pierced or injured.

PMID- 19869247
TI  - EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS.
AB  - 1. Normal guinea pigs exposed to tuberculous cage mates infected
      intraperitoneally and with no cutaneous ulceration readily contract spontaneous
      tuberculosis. 2. The incidence of spontaneous tuberculosis increases with the
      intensity and with the duration of exposure. 3. Spontaneous tuberculosis acquired
      from infected cage mates has with few exceptions the characters of an infection
      which has entered by way of the digestive tract, disease of mesenteric and
      cervical lymph nodes being conspicuous. 4. Guinea pigs exposed to tuberculous
      animals in the same room but not in the same cage may acquire tuberculosis which
      has the characters of a bronchiogenic infection associated with lesions of the
      lungs and tracheobronchial lymph nodes.

PMID- 19869248
TI  - A SPECIFIC FLOCCULATION REACTION OCCURRING BETWEEN ALCOHOLIC EXTRACTS OF
      PNEUMOCOCCI AND ANTIPNEUMOCOCCUS SERUM.
AB  - 1. A flocculation reaction has been described which occurs between alcoholic
      extracts of pneumococci and antipneumococcus serum. 2. The reaction appears to be
      species-specific. It is not strictly type-specific, as slight or moderate cross
      reactions occurred between Type I serums and Type II and Type III extracts. 3.
      The flocculating power of the serum from five horses undergoing immunization with
      pneumococcus, Type I, did not develop to any extent before the end of the 4th or
      5th month. 4. In the case of two of these horses in which it was possible to
      carry out parallel tests on a larger number of subsequent bleedings until the end
      of immunization, some relationship was suggested between the flocculating power
      and the protective titer as ascertained by the routine method of standardization
      in mice.

PMID- 19869249
TI  - AN EXPERIMENTAL STUDY OF GYE'S CANCER THEORY.
AB  - It is obviously impossible to draw definite conclusions as to the significance of
      the differences between our work and Gye's, and still less, of the differences
      between Gye's work and that of Murphy and of Flu. We can only say that in a
      fairly large series of experiments, extending over a period of 12 months, we have
      had absolutely no indication of the necessity of two factors in the production of
      the Rous sarcoma. In other words, we have been unable to duplicate either the
      results of Gye or the modified confirmations of his work by Murphy and Flu. We
      have shown that uncontrollable local and individual variations may produce
      results in occasional chicks which simulate satisfactory experiments, but when
      viewed as a whole, mean nothing. Because of the conflicting nature of results
      obtained by those who have undertaken to repeat the work, and on account of the
      difficulty of controlling all factors involved, we do not feel that it may be
      stated definitely that Gye's theory of the cause of cancer is wrong. On the other
      hand the theory apparently needs more evidence in its support if it is to receive
      further serious consideration. It is suggested, in order to untangle the subject
      as rapidly as possible, that future publications should include sufficient
      consecutive protocols to make the trend of the experiments obvious to the reader.

PMID- 19869250
TI  - DIET AND TISSUE GROWTH : IV. THE RATE OF COMPENSATORY RENAL ENLARGEMENT AFTER
      UNILATERAL NEPHRECTOMY IN THE WHITE RAT.
AB  - The rate of compensatory enlargement of the remaining kidney after unilateral
      nephrectomy has been studied in adult rats fed diets containing various
      concentrations of protein. A curve of enlargement on "standard" food (18 per cent
      casein) shows a rapid initial increase with subsequent slower rise to the 120th
      day. There is no significant difference between the value at 120 days (44 per
      cent) and that at 150 days (48 per cent). A similar series with diets containing
      increasing concentrations of protein but with a constant time interval (21 days)
      after nephrectomy shows an increase in the degree of enlargement directly
      proportional to the protein content of the food. The values vary from 24 per cent
      with the 18 per cent casein ration to 77 per cent with the 90 per cent casein
      diet. A third series shows the enlargement on "high protein" food (85 per cent
      casein). The values vary from 49 per cent at 3 days to 121 per cent at 150 days.
      There is no significant difference between the value at 120 days (123 per cent)
      and that at 150 days (121 per cent). Determinations of total solids on the
      experimental kidneys show that the recorded enlargement involves mainly an actual
      tissue increase.

PMID- 19869251
TI  - A FILTERABLE YEAST-LIKE MICROORGANISM (SCHIZOSACCHAROMYCES FILTRANS, N. SP.).
AB  - A microorganism cultivated in the course of experiments with the virus of hog
      cholera shows the following points of interest. It is pleomorphic in extreme
      degree. Among the forms are coccoid and bacillary bodies at the lower limits of
      visibility. The culture can be completely regenerated after filtration through
      some Berkefeld N filters although these retain Bacillus abortus (Bang). The
      culture is carried forward by multiplication of forms of easy visibility
      (1.5micro). Associated with these at times are still larger forms bearing a
      striking general resemblance to those yeasts which develop abortive mycelia.
      Motile bacillary forms appear to arise as buds or branches from round or ovoid
      cocci. While cognizance is taken of possible alternatives the microorganism is
      provisionally classified with the yeasts and recognizing its filterability is
      named Schizosaccharomyces filtrans. The culture is not pathogenic for swine.

PMID- 19869252
TI  - THE HISTOLOGICAL EXPRESSION OF THE NATURAL RESISTANCE OF RABBITS TO INFECTION
      WITH HUMAN AND BOVINE TYPE TUBERCLE BACILLI.
AB  - From the foregoing description it is evident that when rabbits are inoculated
      intravenously with equal amounts of tubercle bacilli of bovine and human type
      respectively, they are subject to an immediate reaction in the form of an
      interstitial pulmonary exudation, which, being of equal severity and character
      does not serve to distinguish the type. There is an hyperplasia of the lymphoid
      tissue which is much more pronounced in the bovine series and which may
      distinguish this type. Opinion on this point may well be reserved until other
      typical cultures are examined for this response. The two types are sharply
      distinguished by the behavior of the tubercle bacillus and by the progression of
      tubercle formation. Tubercles are formed by both types and for about I week after
      inoculation they are not distinguishable. Progressively thereafter those formed
      as a response to the bovine bacillus become more numerous; they caseate and
      become conglomerate, finally coming to occupy the major part of the pulmonary
      tissue and its associated lymph nodes. With the human type the tubercles do not
      progress to caseation, do not become more numerous after their first well defined
      formation, and finally tend to disappear. The human type bacillus does not
      multiply considerably, if at all, and disappears early. The bovine bacillus
      suffers little or no restraint in growth and finally multiplies enormously. It
      seems clear that so far as histologic evidence goes the fundamental difference in
      the reaction of the rabbit to the two types of tubercle bacilli is referable to
      the ability of the animal to restrain the growth of the human type or to the
      prevalence of conditions which permit a most vigorous multiplication of the
      bovine type. The initial cellular responses seem to be qualitatively of the same
      order and their quantitative distinctions are for the most part developed
      coincidently with the manifest growth of the bovine type bacillus. If we
      undertake to state the observed results in the terminology of immunity we can say
      only that the histologic picture discloses a difference in the rate of bacillary
      multiplication which suggests that a difference in the physiologic requirements
      for growth of the two types of bacilli is satisfied or unsatisfied, in the
      respective cases, by the rabbit as host; or on the other hand, that there is a
      positive growth-restraining action exerted with efficiency against bacilli of the
      human type. It is evident that the present observations furnish no points of
      discrimination between these alternatives. There is, however, an occasional
      result of the injection of human type bacilli into rabbits (not seen in this
      series) which offers a suggestion. When animals so injected are allowed to live
      for 2 or 3 months, the lungs at autopsy not infrequently present a few nodules of
      large size, often 1 cm. in diameter, which are found to be well encapsulated,
      soft, caseous masses. These often contain large numbers of tubercle bacilli.
      Since we know nothing of the particular conditions which give rise to these
      rather exceptional formations it is impossible to draw general conclusions from
      them, but they do suggest that the rabbit is not lacking in the food materials
      required by the human type bacillus; and that if the more usual suppression of
      this type is due to failure of its essential nutritives, it is rather a question
      of the distribution within the animal than an absence which is responsible. The
      usual result would then appear to be due to a positive growth-restraining action
      exerted against the human type bacillus. Certain other points of interest in the
      histologic picture described are worthy of comment. The lymphocytes do not appear
      as active cells in any preponderant way in either series and they are much less
      in evidence in the immune case (human type) than in the non-immune (bovine type).
      This might suggest that the activity of this cell type is a response to infection
      rather than that it furnished an effective preexisting barrier against infection
      in this particular case. If the lymphocytes were the most important agents in the
      immune reaction, it might be expected that they would show an immediate sharp
      response in the human series. The large mononuclear type of cell is clearly most
      closely related physically to the tubercle bacillus within the body of the rabbit
      and this without distinction as to bacillary type. Foci of these cells are the
      loci of the disappearing bacilli of human type, and in either the active or
      necrotic state similar cell collections are the site of the most vigorous
      multiplication of the bovine bacilli. These cells undoubtedly stand in a central
      position in any picture which can be drawn of experimental tuberculosis in the
      rabbit and deserve as a consequence all of the very considerable attention they
      have received at the hands of numerous observers in recent years. It has been
      quite usual of late to consider that the whole of the essential reaction of the
      animal against tubercle bacilli is carried by the cells of the mononuclear
      series, either lymphocytes or large mononuclears according to the predilections
      of the observer. We cannot, however, entirely overlook the presence in very large
      numbers of polymorphonuclear leucocytes, both amphophilic and eosinophilic, in
      this experimental series. They are much less prominent in the animals injected
      with the killed culture and hence can hardly be neglected on the assumption that
      they are merely a part of a reaction to an indifferent foreign body They are in
      large measure a reaction to the living organism: whether a primary and direct or
      a secondary, indirect consequence of its presence we are unable to decide. These
      cells are not massed in any regular relationship to the well formed tubercles or
      to the clusters of mononuclear cells initiating tubercle formation. They are also
      very much less abundant in the very severe late lesions of the bovine type where
      enormous numbers of bacilli are enclosed in the tubercles. It seems possible that
      the polymorphonuclears are a response to the living free tubercle bacilli as
      contrasted with either the dead bacilli or the living bacilli segregated in
      mononuclear cell clusters or in tubercles. They would appear also to be related
      to something apart from the bacillus itself, either a diffusion or disintegration
      product, since phagocytosis of bacilli, or the presence of bacilli in close
      physical relation to polymorphonuclear leucocytes, is so infrequent in general as
      not to have been observed in this series of experiments.

PMID- 19869253
TI  - EFFECT OF AGE ON SERUM LIPOIDS AND PROTEINS.
AB  - The increased inhibiting action of serum with age on the growth of fibroblasts
      has been shown to be due to changes in both the lipoids and the proteins.
      Although the serum protein is less inhibiting than the serum lipoid, the rate at
      which their inhibiting action augments with age is approximately the same. The
      change in the serum protein with age is due to the disappearance of a small
      quantity of growth-stimulating substance, and also to an increase in
      concentration of inhibiting protein. The concentration of all protein fractions
      becomes larger as age advances. The greater inhibiting action of the lipoid is
      associated with a higher concentration of total lipoid and lecithin, and a
      smaller content of cholesterol as the animal grows older. The hypothesis is
      suggested that the inhibiting action of the serum is associated with its
      antienzymatic action.

PMID- 19869254
TI  - THE BACTERICIDAL PROPERTY OF COW'S MILK.
AB  - The bactericidal activity of fresh raw milk from a number of cows has been tested
      with the non-hemolytic mastitis streptococcus. By using this organism and other
      means we were able to rule out the action of agglutinin. The milk of all cows
      examined inhibited the growth of the streptococcus for definite periods. The
      length of the inhibition period varied; the milk from some cows prevented growth
      for 8 hours, that of others for only 4 or 6 hours. The inhibitory action may be
      as strong in the milk of a young cow in its first lactation period as in that of
      an old cow known to be resistant to udder infection. It is possible to absorb the
      streptococcus inhibitory substance by first inoculating the milk with B.
      bovisepticus. We were unable to show that the substance was increased by
      artificial immunization of cows with the streptococcus. Whey obtained by the
      action of sterile rennet solution inhibited the growth of the streptococcus to
      about the same extent as the milk from which it was obtained. We infer that the
      substance originates in the udder since it differs from blood alexin in its
      resistance to heat, it is not increased in the whey although the blood proteins
      are more concentrated, and it is not increased in the milk when the cows are
      artificially immunized or repeatedly exposed to natural infection.

PMID- 19869255
TI  - THE RELATION BETWEEN INVASION OF THE DIGESTIVE TRACT BY PARATYPHOID BACILLI AND
      DISEASE.
AB  - Hog cholera bacilli fed to mice disappear from the stomach within 24 hours, but
      remain and perhaps multiply in the ileum for at least several weeks. They
      promptly penetrate the mucosa and may be found in the spleen. Bacilli introduced
      subcutaneously quickly pass into the intestinal tract where they may be found for
      some weeks. Infected mice may harbor bacilli in the spleen for several months.
      Mice possess a relatively high degree of natural resistance towards hog cholera
      bacilli which gives way to large doses. Disease is probably the result of the
      invasion of the viscera from the digestive tract following feeding, but the
      relation between the dose fed and the numbers penetrating the mucosa is a
      variable one and the conditions favoring such invasion not determined. Contact
      with mice discharging bacilli failed to cause recognizable invasion of the
      digestive tract or the viscera.

PMID- 19869256
TI  - STUDIES ON A PARATYPHOID INFECTION IN GUINEA PIGS : I. REPORT OF A NATURAL
      OUTBREAK OF PARATYPHOID IN A GUINEA PIG POPULATION.
AB  - The course of a natural outbreak of paratyphoid in a normal guinea pig population
      is outlined. A description is given of the gross pathology of the disease. The
      bacteriology of the causal organism is discussed with particular reference to its
      agglutinative affinities.

PMID- 19869257
TI  - STUDIES ON A PARATYPHOID INFECTION IN GUINEA PIGS : II. FACTORS INVOLVED IN THE
      TRANSITION FROM EPIDEMIC TO ENDEMIC PHASE.
AB  - Factors bearing on the maintenance of paratyphoid in an endemic state are
      discussed. There was no evidence of any increase nor any dearly demonstrable
      proof of a decline in virulence of the causative organism. This persisted within
      the breeding stock and it is suggested that the sows constituted the chief focus
      for dissemination of the organism to their young and from these to the population
      at large. Evidence is presented that the carriage of B. paratyphi in the feces
      was of relatively short duration. Fecal carriage of B. paratyphi was commonly
      associated with a localization of the organism in the spleen. Since it is obvious
      that some factor or factors must have changed in the transition from epidemic to
      endemic phase in the presence of younger generations, the hypothesis is
      tentatively presented that the transition from epidemic to endemic phase is due
      to a combination of the weeding out of individuals of low natural resistance with
      a gradual adjustment of the invading organism to the population on a lowered
      level of virulence.

PMID- 19869258
TI  - THE BIOLOGICAL CHARACTERS OF A MUCOID VARIANT OF BACILLUS PARATYPHI FROM GUINEA
      PIGS.
AB  - The biological characters of two mucoid variants of B. paratyphi isolated from
      guinea pigs have been studied and compared with those of the normal type. The
      possible origin of the mucoid type is discussed.

PMID- 19869259
TI  - VIBRIOS FROM CALVES AND THEIR SEROLOGICAL RELATION TO VIBRIO FETUS.
AB  - The calf vibrios thus far studied include one strain serologically distinct from
      the fetal strains. The others are closely related to the fetal strains though not
      identical with them. The pathogenic characters of the calf vibrios, either as
      possible descendents of Vibrio fetus, or as independent factors in the production
      of enteritis have not been demonstrated.

PMID- 19869260
TI  - EXPERIMENTAL BONE MARROW REACTIONS : II. NORMOBLASTOSIS PRODUCED BY INDIA INK.
      THE INFLUENCE OF PREGNANCY ON THIS PHENOMENON.
AB  - 1. Intravenous injections in rabbits of F. Weber Co.'s Drawing Ink gave the
      following results: (a) With large doses, an outpouring of nucleated red blood
      cells, in many instances reaching high values (60,000 to 70,000 per c.mm.),
      accompanied by a slight initial rise of erythrocytes and hemoglobin, followed by
      a moderate anemia and in one animal, a severe anemia. (b) With smaller doses the
      presence of nucleated red cells in the peripheral blood was correspondingly less,
      the hemoglobin and erythrocytes increasing above the initial level. This increase
      was sustained for a considerable time, followed by a decrease to or below the
      initial level. (c) Pregnancy caused a marked suppression, and, shortly before
      delivery, a complete suppression of the normoblastosis. Nucleated red blood cells
      reappeared in the blood after the litter was cast. 2. The filtrate of Weber's
      Drawing Ink, obtained through a Berkefeld filter W, produced the same effects,
      somewhat enhanced, as the whole ink. 3. The bone marrow of the animals injected
      with Weber's ink and the filtrate, both showed a marked erythrocytic hyperplasia,
      with many open sinuses lined with nucleated red blood cells in all stages of
      maturation. 4. As the dialysed ink gave practically the same results, and the
      dialysate proved to be without any effect, the conclusion was drawn that a non
      dialysable protective colloid was responsible for the marked stimulation of the
      hematopoietic organs. 5. The delivery of nucleated erythrocytes was interpreted
      as due to growth pressure induced by rapidly growing red blood cells as well as
      intrasinusoidal formation of erythrocytes. Pressure due to rapidly increasing
      phagocytic cells must also be considered. 6. It is fair to conclude that carbon
      particles as such stimulate endothelial cells mainly toward clasmatocyte
      formation without incapacitating the endothelial cells, while colloidal silver
      apparently had a toxic and incapacitating effect on this system of cells.

PMID- 19869261
TI  - LOCAL IMMUNITY IN EXPERIMENTAL ERYSIPELAS.
AB  - The experiments recorded show that the skin involved in the zone of inflammation
      produced by the endodermal injection of virulent living erysipelas streptococci
      into rabbits becomes, after the lesion has healed, partially but not completely
      resistant to subsequent infection with the homologous organism. In the majority
      of experiments the lesion resulting from the first endodermal injection spread
      downward, i.e., ventrally, to the site of needle puncture forming an oval or
      elongated inflammatory zone. Subsequent injections of the same strain into the
      skin beyond and ventral to the apparent edge of the lesion showed that these
      areas in the supposed direction of the lymph flow likewise became resistant but
      not quite to the same degree as in the inflammatory area. The contiguous areas
      above, behind, and in front of the healed lesion exhibited only a very mild
      degree of resistance. The other side of the rabbit where no previous injections
      had been made reacted as did the normal skin. Repeated injections on the same
      side bring about diminishing local reaction until there is almost no lesion
      following the injection of the standard skin dose. Thus there is a gradual spread
      of skin resistance on the inoculated side, whereas the non-injected side of the
      rabbit reacts normally. Finally, however, after many injections over relatively
      long periods the non-injected side becomes resistant, but at this time, there is
      evidence of general humoral immunity as shown by the presence of agglutinins and
      antitoxin in the blood. The local resistance is apparently not entirely specific,
      for the areas with the previous lesion and ventral to it become more resistant to
      another strain of beta hemolytic streptococcus, though in less degree, and to a
      virulent strain of Staphylococcus aureus to a still less degree. The most
      plausible explanation of the spread of the local immunity ventrally is that the
      streptococci follow the lymph channels. Indeed, in human erysipelas, the
      organisms are recovered by cutipuncture as far as 3 cm. beyond the advancing edge
      of the lesion where there is no gross evidence of inflammation. This aspect of
      local immunity will be considered in subsequent publications. The skin of the
      rabbit involved in the inflammatory reaction following the endodermal injection
      of living streptococci becomes resistant to subsequent injection of the
      homologous strain and of other strains of erysipelas streptococci which are not
      immunologically identical. The local immune areas are resistant but not to the
      same degree to a strain of hemolytic streptococci isolated from follicular
      tonsillitis and to a virulent Staphylococcus aureus. The areas contiguous to the
      local lesion but outside the apparent boundary of inflammation become more
      resistant to subsequent injection. But the regions ventral to those areas become
      more resistant than those dorsal, anterior, or posterior to the inflammatory
      zone. The skin on the non-injected side of the rabbit becomes resistant pari
      passu with the development of humoral immunity.

PMID- 19869262
TI  - BLOOD FIBRIN IN UPPER GASTROINTESTINAL TRACT OBSTRUCTION.
AB  - After high gastrointestinal tract obstruction the blood fibrin increases rapidly.
      The change is more marked in animals with obstruction of the cardiac end of the
      stomach. The rise in fibrin parallels closely the toxemia characteristic of such
      conditions. These results indicate that liver insufficiency cannot be the cause
      of death in such obstructions.

PMID- 19869263
TI  - THE EXCRETION OF NITROGEN AFTER UPPER GASTROINTESTINAL TRACT OBSTRUCTION.
AB  - After obstruction of the cardiac end of the stomach and after obstruction and
      release of the pylorus there is a marked increase in non-protein nitrogen
      excretion. This increase is due to accelerated protein destruction, which may
      result from the great fluid loss, or to the action of some toxic body.

PMID- 19869264
TI  - ETIOLOGY OF OROYA FEVER : VI. PATHOLOGICAL CHANGES OBSERVED IN ANIMALS
      EXPERIMENTALLY INFECTED WITH BARTONELLA BACILLIFORMIS. THE DISTRIBUTION OF THE
      PARASITES IN THE TISSUES.
AB  - The pathological changes observed in the organs in Macacus rhesus monkeys which
      have succumbed to severe infection with Bartonella bacilliformis are similar to
      those found in human organs in persons dying of Oroya fever. The characteristic
      changes in the liver are the zonal necrosis of the cells around the hepatic
      veins, involving active macrophagocytosis of invading polymorphonuclear
      leucocytes in the necrotic areas, and a marked endothelial hyperplasia in the
      sinusoids or around the portal veins. In some instances there is fatty
      infiltration of hepatic cells. In the spleen persistent hyperplasia of the
      endothelial cells of the capillaries leads to the formation of minute foci of
      infarction, owing to occlusion of the lumina. The follicles are dispersed or
      reduced, and there is an active macrophagocytosis of cellular debris,
      polymorphonuclear leucocytes, and erythrocytes. In some specimens an increase in
      normoblasts is noted. Pigment is sometimes present. The lymphatic system shows
      general progressive endothelial hyperplasia, with active invasion of macrophages
      which contain polymorphonuclear leucocytes, erythrocytes, and greenish or dark
      pigments. In the bone marrow there is increased activity of macrophagocytes.
      Numerous normoblasts are found in some instances. In one monkey, sacrificed
      during the course of infection, small, verruga-like nodules were found in the
      lungs and spleen. Bartonella bacilliformis has been detected microscopically,
      though in small numbers, in all tissues showing histological changes. Parallel
      cultural determinations of the presence of Bartonella bacilliformis in the blood,
      liver, spleen, lymphatic glands, bone marrow, and local lesions established the
      relationship between the pathological conditions and the presence of the
      parasite. The organism seems to persist longest in the lymphatic glands. Cultural
      methods offer a simple and conclusive means for the determination of the presence
      or absence of the infecting organism.

PMID- 19869265
TI  - ETIOLOGY OF OROYA FEVER : VII. THE RESPONSE OF THE SKIN OF MACACUS RHESUS AND
      ANTHROPOID APES TO INOCULATION WITH BARTONELLA BACILLIFORMIS.
AB  - Bartonella bacilliformis failed to induce lesions when merely rubbed on the
      surface of the intact skin of a chimpanzee, an ourang-utan, and numerous Macacus
      rhesus monkeys, although when applied to the scarified skin of the same animals
      it gave rise to extensive lesions. Application of infectious material to the
      scarified skin did not always induce verruga lesions, but intradermal inoculation
      almost invariably gave rise to nodule formation. The localization of Bartonella
      bacilliformis in the skin is not, in experimental animals, determined by
      mechanical factors, since scarification of the skin or intradermal injection of
      foreign substances in monkeys infected with Bartonella bacilliformis does not
      give rise to verruga formation. The degree of susceptibility of the skin tissues
      appears to be considerably diminished during the course of experimental infection
      with Bartonella bacilliformis. Inoculation of the scarified skin of infected
      animals gave uniformly negative results, and intradermal inoculation induced only
      a mild local reaction. In a few exceptional instances, however, of animals
      previously infected with the strain of Bartonella bacilliformis derived from a
      human verruga nodule, reinoculation with the same strain gave rise to unusually
      marked reactions. The evolution of the skin lesion induced in experimental
      animals by Bartonella bacilliformis may be divided into four stages, the period
      of incubation, the initial stage, the mature and vascular stage, and the
      regression. In the initial stage the lesion is a pure angioendothelioma, but in
      the stage of full development the histological picture is complicated by
      connective tissue proliferation and occasionally also by penetration of epidermis
      into the lesion. The demonstration of Bartonella bacilliformis in the endothelial
      cells distinguishes the lesion from others which simulate it. The cutaneous
      lesions known as verruga nodular, verruga mular, and verruga miliar have been
      reproduced in monkeys.

PMID- 19869266
TI  - EXPERIMENTS ON THE PRODUCTION OF WASSERMANN REAGINS BY MEANS OF TRYPANOSOMES.
AB  - Since it is known that positive Wassermann reactions prevail in trypanosomiasis
      of rabbits, similar to those in syphilis, trypanosomes were used for an inquiry
      into the cause of this reaction. Injections with dead trypanosomes into rabbits
      proved that these microbes are highly active antigens and suffice in themselves
      to produce strongly positive Wassermann sera, in analogy to the findings reported
      by F. Klopstock with Spirochaeta pallida. Although a number of questions require
      further study, yet it seems likely that this antigenic activity of the microbes
      or their products plays a part in the production of the Wassermann reagins in
      infections with spirochetes and trypanosomes.

PMID- 19869267
TI  - INFLUENCE OF LIGHT ON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE NEOPLASM OF
      THE RABBIT.
AB  - An experiment is reported in which an environment of constant and continuous
      light excluding the shorter ultra-violet rays, and one of constant darkness, have
      influenced the course and character of a malignant disease of rabbits induced by
      a transplantable neoplasm. Under the influence of constant light the level of
      malignancy was observed to be low; under the influence of constant darkness the
      level of malignancy was somewhat lower than in the control animals living under
      ordinary indoor light conditions, but the level was not as low as among the
      animals constantly illuminated. These observations furnish experimental evidence
      in support of the idea that there is a correlation between the external factor of
      light on the one hand and the manifestations of an experimental malignant disease
      on the other.

PMID- 19869268
TI  - THE INFLUENCE OF LIGHT ON THE REACTION TO INFECTION IN EXPERIMENTAL SYPHILIS.
AB  - A series of experiments was carried out for the purpose of determining whether
      the reaction of rabbits inoculated with Treponema pallidum might be influenced by
      their light environment. The conditions compared were (1) diffuse sunlight
      filtered through window glass and subject to variations due to natural causes,
      (2) constant and continuous exposure to artificial light with a wave-length of
      from 3022 to 5790 Angstrom units (Cooper Hewitt), and (3) complete exclusion of
      light. The results showed clearly that each of these conditions produced a
      distinctive effect and that the effect tended to conform to the nature of the
      environmental condition. In general, the efficiency of the reaction to infection
      increased with the amount of light received and with the constancy of the
      exposure.

PMID- 19869269
TI  - AN INFECTIOUS GRANULAR VAGINITIS OF COWS.
AB  - A disease of cows characterized by swelling of the vulva, acute inflammation of
      the vaginal mucosa, accompanied by a more or less profuse mucopurulent exudate is
      described. After the acute inflammation subsides the mucosa becomes studded with
      tiny, round, raised, red nodules which persist 2 or 3 months or longer. The acute
      lesion consists in necrosis of the epithelium and accumulations of leucocytes and
      round cells in the edematous submucosa. The nodules in the later stages are made
      up of densely packed masses of lymphocytes in the submucosa which force the
      epithelial layer outward. A Gram-negative bacillus with tiny polar granules was
      found in the exudate. It measures I to 2micro in length and stains with
      difficulty. The organism was obtained in pure culture by inoculating the exudate
      into tubes of slanted agar to which defibrinated horse blood had been added.
      Growth occurs only in sealed tubes. The organism possesses slight pathogenicity
      for guinea pigs. When freshly isolated cultures were introduced into the vagina
      of heifers or young calves, acute inflammation resulted which terminated in the
      characteristic granular stage of the disease.

PMID- 19869270
TI  - EPIDEMIOLOGICAL STUDIES ON RESPIRATORY INFECTIONS OF THE RABBIT : IX. THE SPREAD
      OF BACTERIUM LEPISEPTICUM INFECTION AT A RABBIT FARM IN NEW CITY, N. Y. AN
      EPIDEMIOLOGICAL STUDY.
AB  - The spread of Bact. lepisepticum infection throughout a population of
      thoroughbred rabbits at a farm in New City, N. Y., was studied over a period of 2
      years. The following observations are noteworthy. 1. 50 to 75 per cent of the
      total mortality was due to Bact. lepisepticum infection. 2. About 50 per cent of
      the stock was affected locally with Bact. lepisepticum "snuffles." 3. "Snuffles"
      and mortality rates showed spring and fall rises and low points during the
      summer. 4. Carrier, morbidity, and mortality rates of various special breeds
      differed consistently and to a marked degree. All reflected the same seasonal
      fluctuations as the total population. 5. Individuals within each breed differed
      in their response to the presence of Bact. lepisepticum; some died of penumonia
      and septicemia; others developed the local nasal infection, "snuffles"; others
      became "healthy" carriers; and a few remained uninfected.

PMID- 19869271
TI  - EPIDEMIOLOGICAL STUDIES ON RESPIRATORY INFECTIONS OF THE RABBIT : X. A
      SPONTANEOUS EPIDEMIC OF PNEUMONIA AND SNUFFLES CAUSED BY BACTERIUM LEPISEPTICUM
      AMONG A STOCK OF RABBITS AT SARANAC LAKE, N. Y.
AB  - These observations have brought out three facts which may be stated briefly as
      follows. 1. An acute respiratory epidemic was incited by mucoid strains of Bact.
      lepisepticum of moderate and uniform virulence. 2. The epidemic was brought about
      not by an alteration in the virulence of the prevailing strains of Bact.
      lepisepticum but by a sudden distribution of virulent organisms among a
      susceptible population hitherto unexposed. 3. Individuals in this population
      showed different degrees of resistance to the infecting bacillus; some died from
      pneumonia and septicemia, while others localized the infection to the nasal
      passages. The significance of these facts has been discussed at length elsewhere
      (4).

PMID- 19869272
TI  - ON THE COLLECTION OF THE ENTIRE EXTERNAL SECRETION OF THE PANCREAS UNDER STERILE
      CONDITIONS AND THE FATAL EFFECT OF TOTAL LOSS OF PANCREATIC JUICE.
AB  - It has been possible by appropriate intubation of the main pancreatic duct of the
      dog to collect the total external secretion of the pancreas under sterile
      conditions. When all of the secretion is thus collected exitus occurs in a
      characteristic way in about a week with anorexia, gastric irritability, vomiting
      and asthenia. The significance of this finding has been briefly discussed. A
      method is also described for the "altercursive" intubation of the pancreas
      whereby the secretion may be collected or allowed to flow back to the duodenum at
      will.

PMID- 19869273
TI  - COMPARATIVE PATHOLOGY OF SOUTH AFRICAN JAGZIEKTE AND MONTANA PROGRESSIVE
      PNEUMONIA OF SHEEP.
AB  - As long as the exact etiology of jagziekte and of progressive pneumonia remains
      unknown, it cannot be said that they are identical, although on the basis of the
      observations detailed above, they certainly appear to be. It is extremely
      doubtful whether it is possible to distinguish between them. In the localities in
      which they occur, each is recognized as an infection quite distinct and apart
      from other better known pneumonias. Predisposing factors which lead to bacterial
      invasion are presumably of great importance in both. We have no precise
      information regarding the organisms concerned, but in both diseases, the initial
      changes are alike and occur in the interalveolar tissue and the subsequent
      proliferations of epithelium and the pneumonia are of the same character and
      apparently follow in exactly the same sequence. Finally, in both diseases, there
      is much fibrosis and the animals inevitably die through depletion of respiratory
      area and pneumonia. The view hitherto held, that jagziekte is a disease
      definitely restricted to the Union of South Africa, is thus rendered improbable.
      Nor does it appear likely that jagziekte is due to a single specific virus acting
      primarily upon the epithelial cells of the lungs, which is is likewise a
      conception widely accepted in South Africa.

PMID- 19869274
TI  - ON THE TRANSPLANTATION OF THE GUINEA PIG SUPRARENAL AND THE FUNCTIONING OF THE
      GRAFTS.
AB  - 1. The suprarenal cortex of the guinea pig can be transplanted autoplastically
      into the abdominal wall and may remain for months, growing to fairly large size.
      2. The suprarenal cortex of the guinea pig can be transplanted homoplastically
      but these transplants usually degenerate after a few months. 3. Small autoplastic
      transplants are capable of maintaining the life of a completely
      suprarenalectomized guinea pig for weeks and large transplants maintain the
      animal indefinitely in good condition. 4. Irritation phenomena follow the
      grafting of suprarenal cortex due to the entrance of epinephrine into this tissue
      during the manipulation involved in removal of the gland.

PMID- 19869275
TI  - THE INFLUENCE OF THYROIDECTOMY, SPLENECTOMY, GONADECTOMY, AND SUPRARENALECTOMY
      UPON THE DEVELOPMENT OF EXPERIMENTAL ATHEROSCLEROSIS IN RABBITS.
AB  - Alimentary hypercholesterolemia acting over a sufficient period of time (in
      rabbits with all organs intact, 110 days or longer) causes deposition of
      cholesterol within the intima of the aorta. Deposition of cholesterol within the
      intima of the aorta initiates the formation of experimental atheromata.
      Thyroidectomy, splenectomy, and gonadectomy augment hypercholesterolemia and
      thereby facilitate and accelerate the development of experimental atheromata of
      the aorta in rabbits. Sublethal suprarenal insufficiency does not increase the
      susceptibility of rabbits to the development of such atheromata.

PMID- 19869276
TI  - THE PRODUCTION OF PURPURA BY DERIVATIVES OF PNEUMOCOCCUS : III. FURTHER STUDIES
      ON THE NATURE OF THE PURPURA-PRODUCING PRINCIPLE.
AB  - 1. The purpura-producing principle of Pneumococcus is non-antigenic in the sense
      that it does not stimulate the formation of antibodies. 2. White mice acquire an
      increased resistance to purpura as a result of repeated injections of toxic doses
      of the purpura substance. 3. The serum of rabbits immunized with the purified
      purpura principle, with "S" and "R" strains of Pneumococcus or with cell
      extracts, autolysates or the nucleoprotein fraction of the organism does not
      confer upon white mice protection against purpura. 4. The purpura principle does
      not exist preformed in the cell, but is rather an autolytic derivative; since it
      is formed only when pneumococci undergo autolysis, and it is not found when the
      autolytic ferments are inactivated. 5. The purpura substance is associated with
      the proteose fraction of active pneumococcus extracts.

PMID- 19869277
TI  - THE RELATION OF THE RETICULO-ENDOTHELIAL SYSTEM TO THE FORMATION OF AMYLOID.
AB  - The facts presented suggest strongly that reticulo-endothelial cells are actively
      concerned in the formation of amyloid. Points in favor of this theory are as
      follows: 1. The appearance of amyloid in places where reticulo-endothelial cells
      are normally present, sometimes in very large number. 2. The formation of early
      amyloid in the small solitary patches, which suggests its local formation. 3. The
      occurrence of solitary patches of amyloid apparently located within the
      capillaries of the liver. 4. The manifold relations between reticulo-endothelial
      cells marked out by phagocytized ink granules, loose ink particles and amyloid,
      described in the text. 5. The impossibility of demonstrating reticulo-endothelial
      cells in areas of forming amyloid by intravenous injections of India ink. 6. The
      delayed appearance of amyloid in animals after blockage of the reticulo
      endothelial cells by repeated intravenous injections of India ink.

PMID- 19869278
TI  - CHANGES IN CARBON DIOXIDE TENSION AND HYDROGEN ION CONCENTRATION OF THE BLOOD
      FOLLOWING MULTIPLE PULMONARY EMBOLISM.
AB  - 1. The production of multiple emboli of the pulmonary capillaries and arterioles
      results in rapid and shallow breathing which may be associated with anoxemia, but
      is not dependent for its occurrence upon anoxemia. 2. Similarly there may occur
      an increase in the partial pressure of CO(2) in the blood as well as an increase
      in hydrogen ion concentration. 3. These changes must be regarded as the result of
      the impaired pulmonary function. 4. They are not, however, the cause of the rapid
      and shallow respirations, since the abnormal type of breathing may occur without
      the attendant blood changes. 5. The characteristic type of response to increase
      in CO(2) tension is an increased rather than a decreased depth of respiration.

PMID- 19869279
TI  - THE EFFECT OF MULTIPLE EMBOLI OF THE CAPILLARIES AND ARTERIOLES OF ONE LUNG.
AB  - 1. Injection of a suspension of potato starch cells into the left branch of the
      pulmonary artery, in quantity sufficient ordinarily to give rise to markedly
      accelerated respirations, resulted in no change in respiratory rate. 2. A method
      for injecting substances into the pulmonary artery or its branches without
      interfering with the blood flow to the lungs has been described. 3. Injection of
      similar material into one lung when the other is excluded from the circulation
      either by ligation or by temporary clamping does give rise to rapid and shallow
      breathing (from a rate of 10 to 15 per minute to one of 60 or over) identical in
      character to that brought about by introducing emboli into both lungs. 4. A
      method for clamping and releasing the pulmonary artery or its branches in a dog
      breathing normally with closed thorax has been devised. This is described in
      detail in another paper. 5. After rapid breathing has been initiated by the
      effect of emboli lodged in the arterioles and capillaries of the right lung,
      reestablishing the circulation in the other lung by releasing the clamp on its
      artery may or may not restore the respiratory rate to its original, normal level.
      6. This discrepancy in results has not been correlated with any difference in
      oxygen saturation of the arterial blood, or in carbon dioxide tension or pH of
      its plasma. 7. It is, however, believed to be related to the gross and
      microscopic anatomy of the lung of which the artery has been temporarily clamped.
      Photomicrographs are published, showing in one dog (No. 3), in which the
      respiratory rate returned to normal, a normal histological picture of the left
      lung, and in another dog (No. 4), in which the rate remained rapid after release
      of the clamp, a picture characterized by congestion and dilatation of arterioles
      and capillaries. 8. The fact that accelerated respirations result from emboli in
      the pulmonary capillaries and arterioles only after a certain quantity of
      material has been introduced, and the fact that emboli in one lung do not
      occasion accelerated respirations unless the circulation through the other lung
      is occluded or abnormal, leads us to the conclusion that the phenomenon is not an
      irritative stimulus due to foreign bodies, but is in some manner related to (a)
      diminution of the pulmonary vascular bed, (b) resistance to the blood flow
      through the lungs or (c) congestion or dilatation of the arterioles and
      capillaries of the lungs.

PMID- 19869280
TI  - OBSERVATIONS ON RESISTANCE TO THE FLOW OF BLOOD TO AND FROM THE LUNGS.
AB  - 1. Embolism of pulmonary arterioles and capillaries produced by the intravenous
      injection of starch grains results in a dilatation of the pulmonary artery and
      the right chambers of the heart. This has been demonstrated both by x-ray studies
      and direct inspection. 2. The dilatation of the pulmonary artery and heart occurs
      synchronously with the acceleration of respirations. 3. Dilatation of these
      structures produced by other means, such as obstruction to the flow of blood to
      and from the lungs, by gradually clamping either the pulmonary artery (cat and
      dog) or pulmonary veins (cat) does not, however, give rise to rapid and shallow
      breathing. 4. The effect of these maneuvers on respiration does not become
      apparent until respirations suddenly cease. 5. Neither does sudden restriction of
      the pulmonary vascular bed by clamping the left branch of the pulmonary artery
      give rise to rapid and shallow breathing, though this procedure may cause an
      increase in CO(2) tension and in hydrogen ion concentration of the blood. 6.
      Since rapid and shallow breathing is not the result of (1) anoxemia, (2)
      increased pCO(2) and hydrogen ion concentration of the serum, (3) restriction of
      pulmonary vascular bed by nearly half, (4) increase in resistance to the flow of
      blood to and from the lungs) (5) the presence of starch grains in the lungs
      acting as a local irritant, it must be the result of the secondary pathological
      changes which occur in the pulmonary parenchyma following embolism. 7. The nature
      of these changes, congestion and edema, has been discussed elsewhere. Whether
      they operate directly on nerve endings or through their influence on lung volume
      and tissue elasticity is not certain. 8. Various important clinical analogies
      have been emphasized.

PMID- 19869281
TI  - STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH
      DISEASE : I. DESCRIPTION OF THE STRAIN OF VIRUS USED. TITRATION AND
      CENTRIFUGATION EXPERIMENTS.
AB  - A strain of foot-and-mouth disease virus was recovered from a cow at the height
      of the disease, and was propagated through at least 261 passages in the guinea
      pig. Considerably over 2000 animals proved susceptible to the virus, and the
      virus could be transferred at will back to cattle and hogs, and then again
      returned to guinea pigs. No natural immunity was discovered in guinea pigs.
      Secondary lesions were easily and regularly induced, thus making this strain
      particularly favorable to experimental purposes. In general, the guinea pig may
      therefore be regarded as the animal of choice for laboratory studies. The guinea
      pig could be infected by different methods of injection in different sites, but
      constant and regular production of primary and secondary lesions-or
      generalization of the disease-followed intradermal "tunneling" in the manner
      described, combined with subcutaneous inoculation of the posterior hairless pads
      of full grown animals. As we have indicated, the virus was peculiarly
      epitheliotropic, which in turn gives support to the opinion that its portal of
      entry may be limited. The active agent could purify itself of chance concomitant
      bacteria in the first passages, in a susceptible animal-a character possessed by
      filter-passing viruses in general. The virus was active in dilutions of
      1:10,000,000. This shows not only the minuteness of the active agent, but also
      the necessity for a change of technique from that employed with larger sized
      infectious agents. Apart from this, the dilution factor is important in
      interpreting mere preservation of the virus rather than multiplication, when only
      early successive subplants in culture experiments are positive. Furthermore, some
      samples of virus were not so active-a factor of twenty-five existed between the
      weakest and strongest samples among fifteen titrated. This indicates that
      comparative tests, as, for example, of survival in different media, should be
      made with the same specimen. In any case, the rate and energy of action of the
      virus were proportional to its concentration, thus differing from the behavior of
      certain enzymes. The incitant is not sedimented by centrifugation. Non
      centrifugability, a property of some other filter-passing, infectious agents, is
      not an indication of the fluid character of the virus, as we have already
      explained. In view of the evidence presented and other tests to be reported
      later, failure of deposition is related to the minute size of the incitant. The
      method of centrifugation has also failed to remove "virucidal bodies" in the
      meaning of Frosch and Dahmen.

PMID- 19869282
TI  - STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH
      DISEASE : II. CATAPHORESIS AND FILTRATION.
AB  - Cataphoresis experiments show that the virus of foot-and-mouth disease carries,
      under ordinary conditions, an electropositive charge. Its isoelectric range is at
      the high point of pH = about 8. Although cultivable bacteria are, as a rule,
      electronegative, yet certain protozoa, such as trypanosomes and spirochetes are
      also electropositive. In respect to charge, then, the virus is different from
      ordinary bacteria, but there is nothing in this finding to indicate an inanimate
      character of the incitant. A knowledge of the charge, however, aids in the
      interpretation of certain filtration phenomena, and indirectly in delimiting the
      size of the virus. In addition, it serves to explain its remarkable resistance to
      certain chemicals-a subject to be dealt with in the next paper of this series.
      Finally, cataphoresis indicates the possible separation of the virus from protein
      particles. Filtration experiments were made with different types of filters:
      Seitz, Berkefeld V and N, and Chamberland, of practically all sizes, collodion
      membranes, and Bechhold's ultrafilter. The results confirm the electropositive
      charge of the virus, as well as the minuteness of its size. Filtration was
      effected through the Seitz, Berkefeld, and Chamberland filters. In regard to the
      latter, the active agent passed through the L 11 only when its charge was shifted
      to negative: under ordinary conditions, carrying an electropositive charge, it
      failed to traverse this more dense wall, and was completely adsorbed in the
      oppositely charged barrier. Filtrations through electronegative collodion
      membranes, prepared in different ways and of varying thicknesses, resulted, as a
      rule, in failure, unless the thinnest and most permeable membranes were employed.
      But in these, the complication of microscopic holes was to be considered. Hence
      this method was regarded as impracticable. Success, however, was obtained with
      Bechhold's ultrafilter membranes of the most permeable type, and with these it
      was possible to measure relatively, by a system of "molecular" filtrations, the
      size of the incitant. This was found to be, in relation to other particles of
      like charge, between 20 and 100 mmicro in diameter. The filtration phenomena of
      the foot-and-mouth disease virus can be accounted for on the basis of the minute
      size of the particles of the incitant carrying an electropositive charge, and no
      evidence can be deduced therefrom that the virus is of a fluid character. For the
      relative size of the particles is constant and the invariability of the limits of
      measurement contradicts the notion that the incitant may be a "solute" varying in
      dimensions in different "solvents."

PMID- 19869283
TI  - STUDIES ON COMPLEMENT FIXATION IN TUBERCULOSIS. III.
AB  - The prolonged extraction of the tubercle bacillus with boiling ethyl alcohol,
      followed by one or more reprecipitations by chilling the hot alcoholic solution,
      easily yields a preparation very active as antigen in the complement fixation
      reaction. This preparation gives a precipitation reaction with high dilution of
      the normal blood serum of a number of species. The precipitation reaction
      presents as a peculiar feature a very long pro-zone and is further dependent on a
      preceding heat treatment of the serum for its demonstration. Occurring as a
      reaction of normal serum, the reaction is apparently not influenced by
      immunization sufficient to develop moderate specific complement fixation
      reactions.

PMID- 19869284
TI  - STUDIES ON IMMUNITY TO PNEUMOCOCCUS MUCOSUS (TYPE III) : I. ANTIBODY RESPONSE OF
      RABBITS IMMUNIZED WITH TYPE III PNEUMOCOCCUS.
AB  - 1. Type III pneumococci fail in the majority of instances to stimulate the
      production of anti-S antibodies. (Type specific agglutinins, type specific
      precipitins, and antibodies affording type specific protection in mice.) 2. Type
      III pneumococci are effective in the stimulation of the production of anti-P
      antibodies (agglutinins for R strains of pneumococci and precipitins for
      pneumococcus nucleoprotein). These antibodies are ineffectual in the passive
      protection of mice.

PMID- 19869285
TI  - INFLUENCE OF LIGHT ON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE NEOPLASM OF
      THE RABBIT : SECOND PAPER.
AB  - Experiments are reported in which an environment of constant and continuous light
      with a wave-length of from 3022 to 5790 Angstrom units, supplied by mercury arcs
      in crown glass, and of constant darkness, have influenced the course and
      character of a malignant disease of rabbits induced by a transplantable neoplasm.
      Under the influence of constant light the level of malignancy was lower than in
      control animals living under ordinary conditions of diffused sunlight. Under the
      influence of constant darkness the level of malignancy was somewhat lower than in
      control animals but the effect of this environment was modified by the special
      character of the disease prevailing at this time. The incidence of bone
      metastases was unusually high, but it was greatly increased in the rabbits kept
      in constant darkness. These observations furnish experimental evidence in support
      of the belief that there is a correlation between the external factor of light
      and the manifestations of an experimental malignant disease.

PMID- 19869286
TI  - EXPERIMENTAL BONE MARROW REACTIONS : III. POLYCYTHEMIA, NORMOBLASTOSIS, AND
      ERYTHROCYTIC HYPERPLASIA OF THE BONE MARROW PRODUCED BY GUM SHELLAC.
AB  - 1. The effect produced by intravenous administration of gum shellac solution
      varied directly with the strength of the solution and the amount injected. (a)
      Strong solutions were intensely toxic and fatal to all the animals injected.
      Toxicity was abolished by the presence of carbon particles in the solution. (b)
      Medium strength solutions produced a marked normoblastosis followed by an
      erythroblastosis if injections were continued, accompanied either by an initial
      rise of red blood cells and hemoglobin followed by a decrease or an initial
      decline followed by an increase. The decrease of erythrocytes and hemoglobin did
      not amount to an actual anemia, and was usually concomitant with the greatest
      outpouring of nucleated red cells. (c) Small doses elicited the same kind of
      response except that the normoblastosis was less marked, the decrease of red
      cells and hemoglobin minimal or absent, the increase of red blood cells and
      hemoglobin marked in most instances. (d) Minimal doses elicited no appreciable
      reaction. 2. The bone marrow in animals killed after a course of injections
      showed intense erythrocytic hyperplasia. This disappeared after a variable length
      of time with a return of the bone marrow to apparently normal condition. 3. Toxic
      effects with non-fatal doses in form of hemorrhages were produced mainly in the
      bone marrow and occasionally in the kidney under the following conditions. (a)
      After one injection in an animal with hyperplastic marrow (hemorrhages ih the
      bone marrow only). (b) After the fourth and fifth dose when administered at long
      intervals (4 to 19 day intervals). (c) After one injection given 40 days after
      several successive injections (one animal only). 4. Small and divided doses
      administered at long intervals produced no apparent ill effect. 5. Subcutaneous
      administrations did not elicit any marked systemic reactions. Locally there was
      induration and edema. 6. The conclusion was drawn that gum shellac solution
      stimulates markedly the production of erythrocytes in the bone marrow. The
      mechanism of stimulation is not clear, but it seems unlikely that it is due to
      destruction of red blood cells in the peripheral blood stream.

PMID- 19869287
TI  - THE EFFECT OF GUM SHELLAC SOLUTION ON THE SURFACE TENSION OF RABBIT SERUM.
AB  - Following the intravenous injection of a gum shellac solution which alters the
      peripheral blood picture there is an increase in the time-drop of the diluted
      serum. This is believed to indicate changes in the physicochemical state of the
      plasma. This gum shellac solution behaves as a surface-active substance; its
      effect on the surface tension of serum is hindered by the du Nouy phenomenon of
      adsorption on serum molecules.

PMID- 19869288
TI  - ETIOLOGY OF OROYA FEVER : VIII. EXPERIMENTS ON CROSS-IMMUNITY BETWEEN OROYA FEVER
      AND VERRUGA PERUANA.
AB  - Nine monkeys (Macacus rhesus) and a chimpanzee which had recently recovered from
      an infection with the Oroya strain of Bartonella bacilliformis were tested for
      immunity against the verruga strain of Bartonella bacilliformis as well as
      against the homologous strain. Complete immunity to both strains was
      demonstrated. The result establishes the identity of the strains and is in
      agreement with the result of comparative serological study. The criteria of
      recovery include not only the subsidence of febrile reactions and local lesions
      but also a negative result of cultural tests of blood and lymphatic gland tissue.
      Recovery may occur as early as 1 month after inoculation, but in most instances a
      period of 2 to 5 months is required for the completion of convalescence.

PMID- 19869289
TI  - A STUDY OF PNEUMOCOCCI ISOLATED FROM HORSES UNDERGOING PNEUMOCOCCUS IMMUNIZATION.
AB  - IT HAS BEEN SHOWN THAT THE PNEUMOCOCCUS MULTIPLYING IN THE TISSUES OF THE
      IMMUNIZED ANIMAL (HORSE) BECOMES ATTENUATED: loses, in varying degrees, its
      virulence, capacity of capsule formation, susceptibility to phagocytosis, and
      type specificity. The antigenic activity as an immunizing agent and the
      production of "soluble specific substance" are also altered. In some instances,
      the typical pneumococcus characteristics may be quickly restored by one or two
      passages through a susceptible animal (mouse). In others, virulence is not
      recovered and the organism remains atypical. Whether these changes are to be
      attributed to the specific action of immune bodies in the tissues, or are to be
      considered as the result of some biologic adaptive process to an adverse
      environment, has not been determined. Proof of the specific action of immune
      bodies is possibly open to question, whereas it is well known that virulence and
      with it some other characteristics are profoundly affected under unfavorable
      conditions in the absence of immune bodies, notably when the organism is grown at
      elevated temperatures or in certain unsuitable media. These studies of
      pneumococci isolated from the infected immunized horse provide opportunities for
      further investigation of the significance of changes in virulence, type
      specificity, and formation of "soluble specific substances" in various forms of
      pneumococcus infection.

PMID- 19869290
TI  - COMPARISON OF A VIRUS OBTAINED BY KOBAYASHI FROM CASES OF EPIDEMIC ENCEPHALITIS
      WITH THE VIRUS OF RABIES.
AB  - Since the symptoms produced in experimental animals by the encephalitic virus of
      Kobayashi and by the virus of rabies are similar, and are accompanied by lesions
      which are indistinguishable, and since a cross-immunity is demonstrable between
      the two viruses, the conclusion is advanced that the specimen of so called
      encephalitis virus isolated by Kobayashi is in reality a specimen of rabic virus.

PMID- 19869291
TI  - THE OCCURRENCE OF DEGRADED PNEUMOCOCCI IN VIVO.
AB  - It is conceivable that a change from the virulent, non-phagocytable S form of
      Pneumococcus to the avirulent phagocytable R form may take place in pneumococcus
      disease, but the experiments here reported do not settle the question whether or
      not this is an important factor in determining the outcome in natural infection.
      It has been shown experimentally that the degradation from the S form to the R
      form actually does take place in cultures of Pneumococcus growing in agar
      subcutaneously embedded in guinea pigs, in agar enclosed in vials subcutaneously
      embedded in rabbits, and spontaneously in the blood stream of infected horses.
      However, it was not possible in any of the experiments here cited to demonstrate
      the complete change from S to R pneumococci before the bacteria disappeared from
      the body. When the intermediate or R forms did appear, they were always
      accompanied and usually exceeded in number by the S forms and all three forms
      disappeared together. S organisms may disappear entirely without evidence of
      first going through the intermediate and R stages. On the other hand, contrary to
      expectations, pure cultures of R forms remained viable in subcutaneous foci for
      weeks although apparently freely accessible to the action of phagocytes. It seems
      of some significance that the R forms appeared early in the vials (inoculated
      with S pneumococci) in immunized and normal rabbits alike, indicating that the
      presence of demonstrable specific immune bodies was not alone responsible for the
      variation of the bacteria. Of some importance also is the fact that R forms were
      never derived from similarly prepared control cultures growing in vitro at the
      same temperature and immersed in normal serum, although the S forms remained
      viable and unaltered for 6 weeks. It is likely that variations of pneumococci do
      not occur readily when S cultures are exposed to normal serum in vitro,
      especially when growing in closed vials under a diminished oxygen supply, for it
      has previously been shown (2) that only slight variation occurs even after
      prolonged (240) transfers in heterologous serum broth in the test-tube. It is
      possible, therefore, that the variation which occurred among pneumococci growing
      in agar vials embedded in normal rabbits was actually provoked by unknown
      influences in the living tissue fluids. Although R forms have been shown to occur
      in vivo, no positive evidence can be derived from these experiments to prove that
      recovery from pneumococcus infection depends upon the degradation of the virulent
      S forms of pneumococci to the avirulent R forms and the subsequent destruction of
      the latter by phagocytes.

PMID- 19869292
TI  - STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH
      DISEASE : III. RESISTANCE TO CHEMICALS.
AB  - The virus of foot-and-mouth disease exhibits a remarkable resistance to such
      bactericidal agents as the narcotic solvents (alcohol, ether, chloroform), or
      such antiseptics as phenol, bichloride of mercury, or cresol, as shown by tests
      made by others and ourselves. We have shown, however, that the resistance of the
      incitant to these chemicals is really masked. It is due to the fact that the
      reagents coagulate the proteins of the medium in which the virus is, as a rule,
      suspended. As a result the active agent is protected by the coagula which
      prevents direct contact with the chemicals. On the other hand, if advantage is
      taken of the periodic phenomenon attending such processes, and coagulation is
      prevented, the virus can then be brought under direct action of the antiseptics.
      Under these conditions, the incitant is more sensitive to destruction by the
      chemicals than is the living staphylococcus. As a corollary, the virus is
      destroyed as rapidly, or even more so, than are staphylococci by substances such
      as sodium hydrate (1 to 2 per cent solutions), or antiformin (1 per cent
      solution) which do not form coagula. We are therefore compelled to contradict the
      opinion that the extraordinary resistance to certain chemicals of the virus of
      foot-and-mouth disease, as it ordinarily occurs admixed with proteins, is an
      indication of its inanimate character. The results of a large series of
      experiments lead to the conclusion that of a number of antiseptics employed the
      sodium hydrate in 1 to 2 per cent solutions is an effective virucide. It is
      capable of killing the virus within 1 minute as shown by tests on cattle and
      guinea pigs. Furthermore, its effectiveness is not diminished even when the
      virulent material is admixed with cattle's urine, with manure, or with garden
      soil. The experimental evidence and the cheapness suggest its use in field
      practice as a disinfectant.

PMID- 19869293
TI  - STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH
      DISEASE : IV. CULTIVATION EXPERIMENTS.
AB  - No multiplication of the virus in vitro was observed. We have found, however,
      that the optimum conditions necessary for the preservation of the virus in
      artificial media are as follows: The hydrogen ion concentration of the medium
      should be 7.5 to 7.6, not only at the beginning, but, and more important, at the
      conclusion of the period of observation. A strict anaerobic atmosphere is also
      favorable, as is a temperature below 37 degrees C. A semisolid structure of the
      medium appears to be advantageous and this can be effected by the use of (1/4)th
      per cent agar or 10 per cent gelatin. Of the two, the gelatin is more desirable,
      and of the latter the most effective material is gelatin from which the
      impurities have been most thoroughly removed, namely the gelatin employed by Loeb
      for his isoelectric determinations. This material is best adjusted to the proper
      hydrogen ion concentration (7.5-7.6) with potassium hydroxide and not with buffer
      phosphate. Gelatin is the simplest of protein media available and its employment
      is in keeping with the principle we have found that the requirements for life of
      the virus of foot-and-mouth disease are of the simplest. The addition of organic
      or complex protein substances, such as dextrose, broth, serum, lipoids, etc., to
      a simple basic medium interferes with the effectiveness of the latter. It is thus
      not surprising that we were unable to confirm the cultural results of Frosch and
      Dahmen for neither their medium nor its components or their method satisfies the
      essential conditions necessary to maintain artificially the life of the virus.
      Furthermore, from the standpoint of technique it was found necessary when
      comparing 2 or more media for their value in preserving the incitant, to employ
      all of them in a parallel experiment with the same sample of virus, for the
      factors of potency of the active agent, contamination, and changes in hydrogen
      ion concentration, if variable, may give rise to faulty interpretations.
      Moreover, activity in 3 successive subplants may be regarded as mere preservation
      but not multiplication of the virus. Finally, we discuss the status of the virus
      from the point of view of its fluid or particulate, and its animate or inanimate,
      characters.

PMID- 19869294
TI  - OXYGEN POISONING IN MAMMALS.
AB  - 1. Oxygen in concentrations of over 70 per cent of an atmosphere is poisonous to
      dogs, rabbits, guinea pigs and mice. 2. The poisonous effects manifest themselves
      in drowsiness, anorexia, loss of weight, increasing dyspnea, cyanosis and death
      from oxygen want. 3. The cause of oxygen want is a destructive lesion of the
      lungs. 4. The lesion may be characterized grossly as an hemorrhagic edema.
      Microscopically there is to be seen in varying degrees of intensity (a) capillary
      engorgement with hemorrhage, (b) the presence of interstitial and intraalveolar
      serum, (c) hypertrophy and desquamation of alveolar cells, (d) interstitial and
      alveolar infiltration of mononuclear cells. 5. The type of tissue reaction is not
      characteristic of an infectious process and no organisms have been recovered at
      autopsy from the heart's blood or from lung puncture. 6. The poisonous effects of
      inhalations of oxygen-rich mixtures do not appear to be related to impurities in
      the oxygen, nor are they related to faulty ventilation, excessive moisture or
      increased carbon dioxide in the atmosphere of the chambers in which the
      experimental animals were confined.

PMID- 19869295
TI  - OXYGEN POISONING IN COLD BLOODED ANIMALS.
AB  - 1. Exposure of frogs to atmospheres containing approximately 95 per cent of
      oxygen is without apparent effect on their state of well being, and produces no
      noticeable changes in the appearance of their web capillaries. 2. Turtles exposed
      to similar atmospheres are also apparently unaffected unless the oxygen be warmed
      to mammalian temperature. 3. At this temperature (37.5 degrees C.) the turtles
      behave like mammals, showing loss of appetite, shortness of breath, death and, at
      autopsy, hemorrhagic extravasations in the lungs. 4. Young turtles are more
      resistant (or adaptable) to this change in environment than mature ones.

PMID- 19869296
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : VII. ON THE PARTICULATE NATURE OF
      BACTERIOPHAGE.
AB  - When filtrates of lysed cultures (bacteriophage) are subjected to prolonged
      dialysis under osmotic pressure against water, the presence of the lytic agent
      can be detected outside the membrane only during the first few days. The residue
      remaining inside the membrane contains the bulk of the original lytic agent, and
      yet it is no longer capable of diffusing into the outer solution. The
      interruption of diffusion is shown not to be due to any alteration in the
      permeability of the membrane. Moreover, the residue fails to diffuse through a
      fresh membrane of similar permeability, while the dialyzed portion of the phage
      passes quantitatively through a new membrane. When ultrafiltration under pressure
      was substituted for dialysis, the residue on the filter could be washed
      repeatedly with water without giving off into the filtrate any more active agent.
      However, if broth was substituted for water, a renewed diffusion of the active
      agent resulted. These results are interpreted as indicating that the colloidal
      particles present in the lytic filtrates (and apparently endowed with properties
      of bacteriophage) do not represent autonomous units of the active agent, but
      merely serve as a vehicle on which the agent is adsorbed. The vary in size within
      limits wide enough to permit fractionation by means of ultrafiltration. When the
      coarser particles retained by the ultrafilter are washed with broth, some of the
      active agent is detached from its coarse vehicle particles. The agent, now more
      highly dispersed, is capable of passing the filter which held it back previously.
      Preparation of a simple ultrafilter used in these experiments is given in detail.

PMID- 19869297
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : VIII. THE MECHANISM OF LYSIS OF DEAD
      BACTERIA IN THE PRESENCE OF BACTERIOPHAGE.
AB  - We have been able to confirm the observations of Twort as well as of Gratia, that
      dead staphylococcus may undergo lysis if, in addition to a suitable
      bacteriophage, there is also present live staphylococcus. Moreover, we have
      endeavored to ascertain the mechanism of this phenomenon and have found that in
      order to elicit it it is necessary to control the numbers of live and dead
      bacteria in the mixture. An excess of dead bacteria interferes with lysis by
      adsorbing the bacteriophage before it has the opportunity to initiate necessary
      changes in the live bacteria, so that all lysis is prevented. The phenomenon is
      specific, that is, the lysis of live bacteria is accompanied by lysis of dead
      bacteria of the same species only. Lysis of dead bacteria occurs best with
      staphylococcus, an organism which easily undergoes spontaneous autolysis under
      appropriate conditions. In the case of B. coli or B. dysenteriae the lysis of the
      dead bacteria is uncertain. Dead bacteria need not be present in the mixture at
      the beginning of the experiment; they will be dissolved if added any time before,
      during, or after the completion of lysis of live bacteria. If the test is
      performed so that a suitable semipermeable membrane is interposed between the
      dead and live bacteria, the dead bacteria are not dissolved, in spite of the
      lysis of live bacteria on the other side of the membrane. The agent determining
      the lysis of dead bacteria is not diffusible, while the principle initiating the
      lysis of live bacteria diffuses freely and is demonstrably present on both sides
      of the membrane. The complete independence of the agent causing dissolution of
      dead bacteria from bacteriophage can also be shown by separating the two agents
      by means of filtration, or by adsorption on bacteria. The ferment-like substance
      responsible for the lysis of dead bacteria is different from the bacteriophage.
      It is not diffusible through collodion, it is easily adsorbed on clay filters, it
      is heat-labile, and is inactivated on standing. An agent possessing identical
      properties was found in cultures of staphylococcus undergoing spontaneous
      autolysis in the absence of bacteriophage, but in this instance the agent
      appeared in the filtrates considerably later than it did when phage was present.

PMID- 19869298
TI  - BACTERIUM LEPISEPTICUM INFECTION : ITS MODE OF SPREAD AND CONTROL.
AB  - In this paper we have attempted to describe the manner of spread of an endemic,
      native, respiratory infection and a method for its control. The essential factor
      determining the prevalence of such an endemic disease is, we believe, host
      susceptibility, which is controlled by hereditary and environmental influences.
      Furthermore, it seems probable that the amount of this population susceptibility
      determines the dosage of specific microbes available to the population. An
      increase in dosage in the herd is followed by an increase in the spread and
      severity of the infection, and a decrease by a corresponding alleviation. Hence,
      two methods for the prevention of epidemics are available: (1) an enhancement of
      population resistance, and (2) the reduction to a minimum of available dosage.
      These procedures have proved successful for 3 years in maintaining a population
      of breeding rabbits, in the midst of a badly infected community, entirely free
      from Bact. lepisepticum infection. Confirmation of the above conclusions has been
      gained from other studies in the field of experimental epidemiology. Dr. D. T.
      Smith (2), at Saranac, New York, found that changes in population susceptibility
      were responsible for a severe outbreak of Bact. lepisepticum infection and
      septicemia. Freund (3), at Berlin, has just published an interesting account of
      respiratory epidemics of rabbits and guinea pigs, apparently brought about by
      sudden changes in temperature and housing conditions. Pneumonia and Pasteurella
      infection, endemic in the population, increased suddenly in extent and severity.
      Nevertheless, neither endemic nor epidemic strains of the microorganisms were
      found to be especially virulent. Dr. Theobald Smith (4), in a study of
      paratyphoid epidemics of guinea pigs, has made similar observations. He noted
      that pregnant females acted as the foci of infection, and that from these
      individuals, presumably of lessened resistance, the bacteria were given off and
      infection was spread. The studies in experimental epidemiology are rapidly
      reaching a stage where they may be applied to the problems of human disease.
      Indeed, more recent observations of the mode of spread of pneumonia (5-7),
      scarlet fever (8), typhoid (9, 10), plague (11), diphtheria (12-14), measles
      (15), and tuberculosis (16-18) increasingly show a tendency to discard the theory
      of fluctuating microbic virulence and to emphasize the importance of the host
      factors.

PMID- 19869299
TI  - A SIMPLE METHOD FOR THE ISOLATION OF PURE CULTURES FROM SINGLE BACTERIAL CELLS.
AB  - A method is described for the isolation of pure cultures from single bacterial
      cells, which is simple in operation and which requires no complicated apparatus.
      In addition to its simplicity, the method possesses the further advantage that
      several selected colonies can be isolated from the same preparation.

PMID- 19869300
TI  - THE CULTIVATION OF LENS EPITHELIUM IN VITRO.
AB  - 1. Differentiation of the posterior cells of the lens vesicle into lens cortex
      has been observed in vitro. 2. It is possible to dissect out the lens of the 5
      day embryo chick in such a manner as to free it from all extraneous cells. 3.
      Lens epithelium even at a very early stage is contained within a cuticula. 4.
      Lens epithelium under proper conditions will live, migrate, divide, and multiply
      in vitro in primary explants. 5. An unmixed strain of lens epithelium can be
      propagated from a primary explant by successive subcultures. This strain can be
      utilized for controlled experiments on the nutrition of the cells of the lens.

PMID- 19869301
TI  - THE ACTION OF THE SYMPATHETIC UPON THE EXCITATORY PROCESS IN THE MAMMALIAN HEART.
AB  - Stimulation of the sympathetic nerve endings, after paralysis of the vagus,
      accelerates the transmission of the excitatory process in the dog's auricle.
      Following the functional exclusion of the vagus ergotamine slows the rate of the
      sinus rhythm, depresses A-V conduction, and delays the transmission of the
      excitatory process in the auricle. The relation of the sympathetic and
      parasympathetic nerves in the control of the cardiac rhythm is discussed.

PMID- 19869302
TI  - EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : THE ELIMINATION OF TUBERCLE BACILLI
      IN THE FECES, BILE, AND URINE OF INFECTED GUINEA PIGS.
AB  - 1. After intraperitoneal inoculation of guinea pigs with tubercle bacilli, the
      microorganisms may appear in the feces and elimination may persist during 1 week.
      Subsequently during several weeks no tubercle bacilli can be recovered from the
      feces. 2. When tuberculosis is widely disseminated in the body of guinea pigs,
      tubercle bacilli are discharged with the feces. 3. Tubercle bacilli are
      occasionally eliminated in the bile of guinea pigs immediately after inoculation
      but are almost constantly found in the bile after several weeks when the disease
      is well established. 4. Tubercle bacilli are eliminated in the urine of
      experimentally infected guinea pigs only when infection is far advanced.

PMID- 19869303
TI  - BACTERIOPHAGE ISOLATED FROM THE COMMON HOUSE FLY (MUSCA DOMESTICA).
AB  - 1. Bacteriophage active against four species of bacteria was found in a salt
      solution extract of house flies. 2. A growth-inhibiting principle, not
      bacteriophage, active against four other species of bacteria was found to be
      present in the same extract. 3. An attempt to secure streptococcus bacteriophage
      by feeding to flies a streptococcus susceptible to the inhibitor but not to the
      bacteriophage of this filtrate was unsuccessful, indicating that the two
      activities are quite unrelated.

PMID- 19869304
TI  - ON THE INFLUENCE OF ACID GROUPS ON THE SEROLOGICAL SPECIFICITY OF AZOPROTEINS.
AB  - The method of partial synthesis of antigens as employed in the foregoing
      experiments obviously cannot be substituted for the chemical study of natural
      antigens. But some questions of a rather general nature not easily accessible to
      investigations of the latter sort, may be approached by the use of artificial
      protein compounds. Thus the results reported indicate a peculiarity of certain
      chemical structures such as acid radicals. The group of immune sera obtained by
      injecting azoproteins made from non-acid azo components had a wide range of
      activity. Substituents like CH(3), OCH(3), NO(2), Cl, Br, I, in the aromatic
      nucleus altered the reactions to a moderate degree only, in most cases. The
      effects were dependent more on the position than on the nature of the
      substituents. Two substances were found, however, which had a pronounced effect
      on the specificity of the compound protein, namely acetyl-para-phenylenediamine
      and para-aminoacetophenone. In consideration of the above facts it is uncertain
      whether the antigenic changes noticed by Obermayer and Pick (7) after treating
      proteins with nitric acid, nitrous acid or iodine are mainly due to the
      substitution of hydrogen in the benzene ring by NO(2) and I, as is the general
      belief, or to other changes of the protein. This question had been raised already
      by the observation that the proteins treated with HNO(3) or HNO(2) containing
      respectively the nitro or the diazo group, did not differ substantially in their
      serological properties (8). The antigens made from acid compounds form a group
      with distinctive features. In the first place the presence of acid radicals
      destroys the reactivity with the immune sera for the non-acid substances. This
      influence is so marked that even the reaction with the species specific part of
      the protein, if such is present, appears to be diminished. Also the sera produced
      with the acid antigens react but feebly with the non-acid azoproteins.
      Accordingly it was possible to show that by hydrolysis of the ester of an
      aromatic acid contained in an azoprotein the serological reactions of the antigen
      underwent a radical change. The presence of a free carboxyl group in the antigens
      not only determines the characteristics mentioned but there is reason to believe
      that it increases markedly the degree of specificity exhibited by the antigens
      and the corresponding immune sera, when cross-tests are made with a number of
      acid azoproteins and their antisera. This is brought out by a comparison of the
      results of the present investigation with those described previously (3). It is
      of interest in this respect that the specific carbohydrates found by Avery and
      Heidelberger in pneumococci and pneumobacilli are mostly, if not in all cases,
      compounds of distinctly acid character.

PMID- 19869305
TI  - THE DEVELOPMENT OF AGGLUTININS AND PROTECTIVE ANTIBODIES IN RABBITS FOLLOWING
      INHALATION OF PNEUMOCOCCI.
AB  - 1. Following repeated inhalations of Type I pneumococci agglutinins and
      protective antibodies can be demonstrated in the serum of rabbits. 2. The
      percentage of rabbits whose serum shows agglutinins remains stationary after the
      5th exposure, but the percentage of rabbits showing protective antibodies in
      their sera steadily rises.

PMID- 19869306
TI  - THE RESPONSE TO RESPIRATORY RESISTANCE : A COMPARISON OF THE EFFECTS PRODUCED BY
      PARTIAL OBSTRUCTION IN THE INSPIRATORY AND EXPIRATORY PHASES OF RESPIRATION.
AB  - 1. A study has been made of the effects of resistance to respiration in the
      inspiratory and expiratory phases. 2. Resistance to inspiration caused an
      increase in respiratory rate, a decrease in tidal air, and in most instances a
      severe limitation of the minute volume of pulmonary ventilation. Anoxemia and
      acidosis accompanied these changes. 3. When resistance was removed the
      respiratory rate continued to be rapid, but the tidal air and minute volume
      increased. As a result of this there was a fall in pCO(2), a rise in pH, and in
      some cases a complete disappearance of anoxemia. 3. Resistance to expiration
      slowed the respiratory rate and produced a constant decrease in the minute volume
      of pulmonary ventilation. Anoxemia and carbon dioxide retention occurred, but
      were less pronounced than in the inspiratory experiments. Release of resistance
      to expiration resulted in a return of all functions to their normal, or
      approximately normal, levels. 4. A difference in the gross pulmonary pathology
      found at autopsy in these two types of experiments has been described, and an
      attempt has been made to correlate changes in function with changes in structure.
      5. No direct evidence has been supplied for the liability to fatigue of the
      respiratory center.

PMID- 19869307
TI  - A FURTHER STUDY OF BLOOD REACTION AND BLOOD GASES IN PNEUMONIA.
AB  - Estimation of the blood reaction and of blood gases in a series of nineteen
      individuals suffering from pneumonia failed to reveal a condition of acidosis
      occurring at any time during the disease. The results of this study are
      corroborative of a previous one, to which reference has been made.

PMID- 19869308
TI  - STUDIES ON IMMUNITY TO PNEUMOCOCCUS MUCOSUS (TYPE III) : II. THE INFECTIVITY OF
      TYPE III PNEUMOCOCCUS FOR RABBITS.
AB  - THE OBSERVATIONS RECORDED IN THIS PAPER ON THE INFECTIVITY OF TYPE III
      PNEUMOCOCCI FOR RABBITS MAY BE SUMMARIZED AS FOLLOWS: 1. Of eleven strains of
      Type III isolated from human sources, ten were found to possess low virulence for
      rabbits. This was true despite the fact that all the strains tested possessed
      large capsules and a high degree of virulence for mice. 2. One strain of Type III
      pneumococcus was rendered highly virulent for rabbits. Since it possessed no
      other biological property demonstrably different from the other strains, its
      virulence must reside in some additional property. 3. An initial decrease in the
      number of circulating organisms following the injection of virulent bacteria is a
      well known occurrence, and it was observed in rabbits injected with the rabbit
      virulent strain of Type III. However, the extent of the reduction was in inverse
      proportion to the degree of virulence of the strain; a fact which makes
      mechanical explanations of the phenomenon insufficient. 4. The bacteremia
      produced in rabbits by Type III pneumococci, avirulent for this species, runs a
      characteristic course. It differs from that produced by non-encapsulated R forms
      of pneumococci although in both instances survival of the infected animal ensues.
      This is evidence that the mechanism of resistance against encapsulated and non
      encapsulated pneumococci is not identical. 5. Phagocytosis of Type III
      pneumococci by circulating rabbit leucocytes was not demonstrable by a vital
      stain technique, whereas under the same conditions the ingestion of non
      encapsulated R forms occurred. This is further evidence that the process whereby
      non-encapsulated pneumococci are disposed of, is insufficient to explain the
      natural resistance of rabbits to infection with encapsulated Type III
      pneumococci.

PMID- 19869309
TI  - STUDIES ON BACTERIAL ENZYMES : IV. THE MALTASE AND LIPASE OF THE BOTULINUS
      BACILLUS.
AB  - Botulinus bacilli yield a maltase and a lipase, which retain their hydrolytic
      activity independent of the presence of the formed bacterial cell. The maltase is
      an endocellular substance, while the lipase is extracellular. The lipase, when
      separated from the anaerobic bacillus, does not seem to be affected by exposure
      to air.

PMID- 19869310
TI  - STUDIES ON BACTERIAL ENZYMES : V. THE CARBOHYDRASES AND LIPASE OF THE WELCH
      BACILLUS.
AB  - The carbohydrases (maltase, lactase, sucrase, raffinase, amylase) and lipase
      (tributyrinase) of the Welch bacillus retain their hydrolytic activities in
      sterile solutions of the bacterial cells. The demonstration of the carbohydrases
      and detection of their hexose products constitute experimental proof that Welch
      bacilli attack complex carbohydrates by way of a preliminary hydrolysis. The
      result of experiments on the oxidation of the enzymes show that the inhibitory
      effect of air upon the initiation of growth of the living Welch bacillus does not
      include a comparable effect upon the activity of its hydrolyzing enzymes.

PMID- 19869311
TI  - VARICELLA IN MONKEYS : NUCLEAR INCLUSIONS PRODUCED BY VARICELLA VIRUS IN THE
      TESTICLES OF MONKEYS.
AB  - The eosin-staining nuclear inclusions found in the monkeys' testicles inoculated
      with emulsified tissue of human chicken-pox lesions are specifically associated
      with the virus of varicella.

PMID- 19869312
TI  - PHYSICAL, CHEMICAL, AND BIOLOGICAL STUDIES ON THE VIRUS OF VESICULAR STOMATITIS
      OF HORSES : COMPARISON WITH THE VIRUS OF FOOT-AND-MOUTH DISEASE.
AB  - A taxonomic study of the virus of vesicular stomatitis is presented along with
      evidence additional to that already reported(1) to show the similarity of this
      virus to that of foot-and-mouth disease. The connection of the two is discussed
      and the deduction drawn that their generic relationship is close. On the
      contrary, the differences between these two viruses and the herpetic are
      sufficiently marked to indicate a lack of generic connection among the three. The
      results of a comparative study on the effects of particular wave-lengths and
      energies of monochromatic ultra-violet light on the virus and on Staphylococcus
      aureus reveal that the adsorption of specific energies by the two is parallel.
      Since the adsorption of specific energies is an index of chemical character,
      these experiments suggest that the virus is similar in character and chemical
      constitution to bacterial protoplasm.

PMID- 19869313
TI  - THE INFLUENCE OF OVARIECTOMY ON THE SPONTANEOUS OCCURRENCE OF MAMMARY CARCINOMAS
      IN MICE.
AB  - 1. Castration of female mice between 15 and 22 days of age entirely prevented the
      occurrence of spontaneous adenocarcinoma of the breast, while the non-breeding
      control mice of the same strain showed a tumor incidence of 78.5 per cent. 3 of
      the spayed animals developed a spontaneous spindle cell sarcoma. This indicates
      that the influence of the ovary on the development of breast carcinomas is a
      specific one, since ovariectomy does not lead to a resistance against other types
      of spontaneous tumors. 2. Castration between 2 and 6 months of age led to a
      marked reduction of the tumor incidence, but did not entirely prevent the
      occurrence of mammary tumors. 3. It is concluded that the spontaneous mammary
      carcinoma of the mouse is due to a hereditary organ disposition, which remains
      latent in the absence of ovarian function, but which becomes manifest when a
      certain amount of ovarian hormone, corresponding to 5 to 30 estrus cycles, has
      acted on the breast tissue.

PMID- 19869314
TI  - FURTHER OBSERVATIONS CONCERNING GROWTH REQUIREMENTS OF HEMOPHILIC BACILLI.
AB  - 1. 19 strains of non-hemolytic hemophilic bacilli were studied. 17 required the
      addition of V and X growth accessory factors to their media, 2 required the
      addition of only V. 2. Of 15 strains of hemolytic hemophilic bacilli examined, 10
      were found to require the addition of only V to their media, 3 the addition of V
      and X in the form of yeast extract and hematin, and 2 the addition of accessory
      growth factors in the form of blood. 3. In media to which neither V nor X had
      been added true symbiosis was found to occur on growing B. hemoglobinophilus
      canis, requiring the addition of X, with B. parainfluenzae, requiring the
      addition of V, or with hemolytic strains of bacilli, requiring the addition of
      only V.

PMID- 19869315
TI  - SURFACE TENSION OF SERUM : XV. THE THICKNESS OF THE MONOLAYER OF RABBIT PLASMA.
AB  - Experiments are reported which indicate that a shift toward higher concentrations
      is observed in the minimum value of the static surface tension when plasma
      instead of serum solutions is used. The amount of the shift, expressed as a
      function of the concentration, shows that the figures are in satisfactory
      agreement with the determined amount of fibrinogen in the plasma. Some evidence
      is given that "plasma molecules" capable of organizing themselves on adsorbing
      surfaces exist in plasma, and that their length would be approximately 4.3
      mmicroin round figures,instead of 4.0 mmicro for the serum. The area occupied in
      the plane of adsorption by one individual molecule is, however, smaller than that
      occupied by the "serum molecule," thus indicating a marked structural difference
      between the two, the "plasma molecule" being narrower but longer than the "serum
      molecule." This difference may be due either to a different orientation
      accompanied by an increase in one of the dimensions, or else to an actual
      difference in structure with respect to the main axis, resulting in a decrease in
      the mean diameter of the "serum molecule" with an increase in the length of its
      main axis. The mass of the "plasma molecule" is about 6.3 per cent larger than
      that of the "serum molecule, " in the case of rabbit serum.

PMID- 19869316
TI  - IMMUNOLOGICAL PROPERTIES OF A TYPICAL (S-PRODUCING) AND A DEGRADED (NON-S
      PRODUCING) STRAIN OF TYPE II PNEUMOCOCCUS WITH SPECIAL REFERENCE TO PROTECTIVE
      ANTIBODIES.
AB  - The loss of the specialized function of S production by Type II pneumococcus was
      accompanied by a loss of the antigenic properties involved in both active and
      passive protection of mice. Absorption of Type II serum with S-producing
      pneumococci removed all the protective antibodies, as well as the type-specific
      agglutinins and S precipitins. The same absorption treatment of the serum by non
      S-producing pneumococci failed entirely to remove the type-specific antibodies
      and did not affect the protective value of the serum. Absorption with bacteria
      free culture fluids containing the reactive carbohydrate removed the protective
      antibodies as completely as absorption with the whole bacterial cells of type
      specific strains. The results taken as a whole indicate that the antibodies
      involved in the usual protection of mice against Type II pneumococci are closely
      related, if not identical, to the specific anticarbohydrate precipitin.

PMID- 19869317
TI  - FACTORS INVOLVED IN THE INFECTION OF MICE AFTER VACCINATION WITH TYPE II
      PNEUMOCOCCI.
AB  - A group of mice was vaccinated against Type II pneumoccci and subsequently tested
      for immunity against different numbers of the live bacteria. The immunity tests
      were conducted within two zones of dosage. In the first zone where the doses were
      kept within reasonable limits (10(-6) to 10(-3) cc. of culture), the number of
      invading bacteria was without influence and the occurrence of infections was
      determined by the previous immunity response of the individual. In the second
      zone of dosage (where passive protection also fails), these relations were
      reversed, and invasion by overwhelming numbers of the bacteria invariably
      produced infection regardless of the previous immunity response of the
      individual. These results present an extreme example of the importance of the
      immunity response of the individual as a factor always concerned in the
      effectiveness of vaccination.

PMID- 19869318
TI  - STUDIES ON PATHOGENIC B. COLI FROM BOVINE SOURCES : I. THE PATHOGENIC ACTION OF
      CULTURE FILTRATES.
AB  - The relatively young bouillon filtrates, 24 and 48 hours old, of certain strains
      of B. coli obtained directly from the ileum of scouring calves, were highly toxic
      for calves about 1 month old, as well as for older calves and cows when given
      into a vein. The symptoms, of panting followed by dyspneic and jerky respiration,
      indicate some at first obstructive action upon the alveolar and endothelial
      cells, followed by a greater permeability and eventual filling up of the air
      spaces with a serous, fibrinous, and hemorrhagic exudate. Similar effects are
      produced in other organs, such as liver and kidneys, if the toxin reaches them or
      is formed there by multiplying bacteria. There are no immediate or remote effects
      resembling those on calves following the intraperitoneal or the intracardiac
      injection of B. coli filtrates into guinea pigs even when the dose represents
      many multiples, per body weight, of the dangerous or even fatal calf dose. The
      administration of the filtrate subcutaneously is without visible effect.
      Similarly, feeding large numbers of living bacilli produced no manifest
      disturbances. In support of the hypothesis of a genetic relation between the
      group of B. coli and of paratyphoid, a similar but less severe effect was
      produced in a calf by the intravenous injection of a bouillon filtrate of a
      paratyphoid strain.

PMID- 19869319
TI  - STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS : II. THROMBUS FORMATION IN
      NORMAL BLOOD IN THE EXTRACORPOREAL VASCULAR LOOP.
AB  - Thrombus formation has been studied in normal rabbits with an experimental method
      of establishing extracorporeal circulation. In the normal animal circulation in
      the extracorporeal loop usually ceases in from 6 to 10 minutes, or at most, in
      very large and vigorous animals, in 25 minutes.(1) Cessation of the circulation
      is due most frequently to obstruction of the venous cannula (sometimes of the
      arterial cannula) by a mass of white thrombi and secondary fibrin formation
      around it. The site of the clot is determined somewhat by the swiftness of the
      blood stream. In the collodion tube red mural thrombi are obtainable as a rule.
      They are flat and present a wide base resting on tiny white thrombi. After the
      complete obstruction of the circulation, the blood in the apparatus clots very
      rapidly. When the obstruction occurs very quickly either in the arterial or
      venous cannula, or when the blood stream is very slow, the clotting in the loop
      may occur before platelets are laid down in large numbers or before the formation
      of the white thrombi is evident. Mixed thrombi are found in the jugular vein, and
      have their inception in the white thrombi, in the cannula or from the injured
      intima. They extend in the direction of the blood flow.

PMID- 19869320
TI  - STUDIES ON PATHOGENIC B. COLI FROM BOVINE SOURCES : II. MUTATIONS AND THEIR
      IMMUNOLOGICAL SIGNIFICANCE.
AB  - On agar plates certain strains of B. coli from the ileum of calves suffering from
      diarrhea or scours promptly mutate and give rise to forms which have lost
      capsular substance, whose virulence has been greatly reduced, and which have
      gained very greatly in agglutinability and in being taken up by leucocytes. The
      original characters are not regained in cultures kept in the cold after
      development, nor in rapid transfers in bouillon, nor in passages through the
      peritoneal cavity of guinea pigs. Filtrates of 48 hour bouillon cultures contain
      as much toxin in the (b) as in the (a) form indicating no loss in this function.

PMID- 19869321
TI  - STUDIES ON PATHOGENIC B. COLI FROM BOVINE SOURCES : III. NORMAL AND SEROLOGICALLY
      INDUCED RESISTANCE TO B. COLI AND ITS MUTANT.
AB  - The interrelations between bacterial toxins, bacterial capsular (mucoid, viscid)
      substance, and certain normal protective factors in the guinea pig are studied
      with the aid of bacterial mutants and immune serum, and the results formulated in
      an hypothesis.

PMID- 19869322
TI  - STUDIES ON PATHOGENIC B. COLI FROM BOVINE SOURCES : IV. A BIOCHEMICAL STUDY OF
      THE CAPSULAR SUBSTANCE.
AB  - 1. The soluble specific substance obtained from a capsulated strain of B. coli is
      not identical with any specific substance heretofore described. It is a
      carbohydrate, composed of 80 per cent of hexose, probably partly of dextro- and
      partly of levorotatory sugar, since the rotation of the hydrolysate is low.
      Glucuronic acid is probably present in the molecule. 2. Crude "residue" or
      specific substance obtained from the uncapsulated mutant was about 100 times less
      active with homologous serum than similar material from the capsulated strain.
      This supports the view that capsular substance and soluble specific substance are
      the same. In cases where there is a well marked capsule, the specific substance
      is probably produced in greater amount and located peripherally. 3. Capsular
      substance is probably significant for virulence when functioning as a
      morphological capsule. It is present in filtrates of young culture only in very
      small amounts.

PMID- 19869323
TI  - THE SURFACE COMPOSITION OF THE TUBERCLE BACILLUS AND OTHER ACID-FAST BACTERIA.
AB  - Acid-fast bacteria in the boundary surface between salt solution and a test oil
      (tricaprylin) are spontaneously wet and enveloped by the oil. This behavior
      contrasts with that of all other cells studied by the interfacial tension method.
      Four strains of human tubercle bacillus and an atypical bovine strain are an
      exception to the first statement above. These have possessed stability in the
      saline-oil interface; this stability is slight, however, and not comparable with
      that of non-acid-fast bacteria. Acid-fast bacteria subjected to prolonged
      extraction with alcohol show resistance to wetting by oil comparable to that of
      non-acid-fast bacteria. These "defatted" bacteria nevertheless retain their acid
      fast staining properties. Acid fastness cannot then depend on the integrity of a
      surface membrane. Study of the cataphoresis of acid-fast bacteria by Freund has
      rendered the presence of protein in the surface highly probable. We are forced
      then to regard the surface of acid-fast bacteria as complex, containing at least
      lipoid and protein. Not improbably also carbohydrate is present.

PMID- 19869324
TI  - ON THE MECHANISM OF THE SERUM SENSITIZATION OF ACID-FAST BACTERIA.
AB  - Serum sensitization of the acid-fast bacteria causes two definite and directly
      observable changes in the bacterial surface: 1. A change from a surface readily
      wet by oil to a surface more readily wet by aqueous salt solution than by oil.
      This change is observed by microscopic examination of the bacteria in a saline
      oil interface; thus detected, the surface alteration is said to constitute a
      "positive interface reaction." 2. An increased cohesiveness of the sensitized
      bacteria. This may be detected either by centrifuging the bacteria and then
      shaking up the sediment (resuspension reaction), or by observation of the clumps
      in the saline-oil interface. The interface reaction is serologically specific and
      confirms the existence of qualitative differences among acid-fast bacteria. The
      interface reaction parallels the binding of agglutinins as detected by the
      resuspension reaction, but not agglutination as ordinarily tested for. The
      interface reaction is less sensitive,-i.e., gives lower titers-than the
      resuspension reaction in about the average ratio of 1:3. The interface reaction
      in most instances runs approximately parallel to the complement fixation
      reaction; under at least one set of conditions, however, the interface reaction
      is correlated with the binding of agglutinin but not with the complement fixation
      reaction. How much of the bacterial surface must be covered with agglutinin in
      order to produce agglutination varies greatly with the bacterial strain used. The
      bacterial surfaces are modified by treatment with fresh normal sera in a manner
      quantitatively less but qualitatively not observably different from the effects
      of immune sera. Heating normal human, sheep, goat, or rabbit sera for 30 minutes
      at 56 degrees C. has usually diminished but not abolished their effect on the
      bacterial surface. Similar inactivation of guinea pig sera left them without
      detectable effect on the bacterial surface. The agglutination prezone is shown to
      be due to interference by excess colloidal material with the collisions of the
      bacteria prerequisite to clumping. The prezone maybe abolished by centrifugation
      and resuspension of the sediment. Antibodies may be partially dissociated from
      the sensitized bacteria by alkali, with return of the bacterial surface toward
      its normal, unsensitized condition. A carbohydrate yielding on hydrolysis a
      positive pentose test has been detected in the specific alcohol extracts of acid
      fast bacteria studied by Furth and Aronson.(27) The tentative suggestion is made
      that the alcohol-soluble antigens of acid-fast microorganisms may be conjugated
      lipins owing their specificity to carbohydrate haptenes. Protective
      antipneumococcus globulins after heat denaturation have shown behavior in the
      saline-tricaprylin interface indistinguishable from that of maximally sensitized
      acid-fast bacteria. This strengthens the evidence suggesting that sensitized
      bacteria are coated with denatured globulin.

PMID- 19869325
TI  - STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS : III. EFFECTS OF CERTAIN
      ANTICOAGULANTS (HEPARIN AND HIRUDIN) ON EXTRACORPOREAL THROMBOSIS AND ON THE
      MECHANISM OF THROMBUS FORMATION.
AB  - 1. Effects of anticoagulants, heparin and hirudin, on extracorporeal thrombosis
      were studied in thirty-three experiments by means of the extracorporeal vascular
      loop. In spite of adequate single doses of the anticoagulants white thrombi are
      formed and obstruction to flow may follow in the course of time, but the
      formation of red thrombi is markedly retarded. 2. The new method throws some
      light on the mechanics of thrombosis. The influences of foreign surfaces, of
      irregularities on the surface of the vessels, of whirlpools and of eddying motion
      of the blood current and of slowing and of stagnation with consequent prolonged
      contact with foreign surfaces are demonstrated, and these are analyzed in respect
      to the laying down of platelets and leucocytes. 3. The structure of white thrombi
      formed after anticoagulant injection is almost identical with that described by
      Welch. In one respect, however, the present results appear to differ from his:
      the formation of fibrin is postponed and retarded, and hence the collections of
      platelets are deposited in greater amount.

PMID- 19869326
TI  - IMMUNIZATION EXPERIMENTS WITH LECITHIN.
AB  - In testing several egg lecithin preparations prepared by ourselves it was found
      that they did not react in complement fixation tests with immune sera made by
      injections with commercial egg lecithin Merck. With the flocculation method two
      of the preparations reacted only faintly. Also the brain lecithin and
      hydrolecithin gave no distinct reactions. The immunization experiments of Sachs
      and Klopstock could easily be confirmed when commercial egg lecithin Merck was
      used for the injections. Immunizations with brain lecithin and hydrolecithin
      yielded no active sera. With an egg lecithin (No. 1) prepared by us the results
      were not satisfactory though a great number of injections was made. Only one
      serum gave reactions of medium strength by complement fixation and in
      flocculation tests with emulsions of Merck lecithin. It did not react however
      with the lecithin preparation No. 1 itself. In this respect the results resemble
      to a certain degree those of Sachs and Klopstock with their lecithin Bohringer
      immune serum. While the reactions of Merck lecithin were slightly diminished by
      the removal of cholesterol) addition of cholesterol to the lecithin No. 1 had no
      marked effect on the complement fixation tests, even when a larger amount was
      added than that present in the Merck preparation. The cholesterol content of this
      lecithin therefore does not suffice to account for the difference in the results.
      It is noteworthy that our lecithin immune serum No. 967 gave complement fixation
      with emulsions of cholesterol although this substance was not present in the
      injected material. There are several plausible explanations for our results.
      According to one, the production of antibodies for lecithin would depend on
      certain physicochemical conditions of the emulsion injected or upon the presence
      of auxiliary substances in the lecithin preparation (cf. Sachs and Klopstock).
      Another possibility is that the active agent inducing the formation of antibodies
      is not lecithin itself but some other substance present in the active lecithin
      preparations. With regard to the latter assumption it may be mentioned that we
      obtained definite immunization effects from several injections of quantities as
      little as 0.2 mg. of purified preparations of Forssman's heterogcnetic haptene
      mixed with pig serum.(2) To decide between the alternative explanations, further
      studies are necessary.

PMID- 19869327
TI  - DIET AND TISSUE GROWTH : V. THE EFFECT OF DIETARY PROTEIN ON THE REMAINING KIDNEY
      OF ADULT WHITE RATS FOLLOWING A UNILATERAL NEPHRECTOMY.
AB  - The effects of the ingestion of diets containing different concentrations of
      protein on the remaining kidney in adult white rats after a unilateral
      nephrectomy has been studied. In the animals on the high protein diet (85 per
      cent casein), actual glomerular and tubular lesions were observed in the kidneys
      of animals maintained for 90, 120 and 150 days after nephrectomy. In the animals
      on the standard ration, 18 per cent casein, no significant renal lesions were
      observed within the experimental period. Spontaneous focal lesions in the kidneys
      of rats maintained on Sherman's diets "A" and "B" were inconspicuous at the age
      of 350 days but became progressively more frequent and were commonly observed
      after 500 days. The animals on the high protein and standard rations were all
      under 350 days old at the completion of the experiment. It is suggested that the
      age factor is of importance in that young animals may have greater powers of
      adaptation in withstanding the injurious effect of high protein rations. The
      animals on the high protein ration excreted definitely larger quantities of
      protein in the urine, and showed a higher incidence of casts in periods roughly
      corresponding to those in which anatomic lesions were observed than did the rats
      on the standard diet.

PMID- 19869328
TI  - CELL RESPIRATION STUDIES : I. A MICROSPIROMETER FOR THE CONTINUOUS STUDY OF THE
      OXYGEN ABSORPTION BY LIVING CELLS.
AB  - A description is given of a closed space respiration apparatus which can be used
      to determine the amount of gas used or liberated by living blood or tissue cells,
      or chemical substances. Continuous observations can be made and repeated
      measurements recorded without interrupting the vital processes or destroying the
      cells. Studies of the oxygen consumption by whole blood in normal individuals and
      in patients with leucocytosis and myelogenous leucemia, as well as by white cells
      suspended in plasma, will be reported in subsequent papers.

PMID- 19869329
TI  - CELL RESPIRATION STUDIES : II. A COMPARATIVE STUDY OF THE OXYGEN CONSUMPTION OF
      BLOOD FROM NORMAL INDIVIDUALS AND PATIENTS WITH INCREASED LEUCOCYTE COUNTS
      (SEPSIS; CHRONIC MYELOGENOUS LEUCEMIA).
AB  - 1. The oxygen consumption of blood of normal individuals, when the hemoglobin is
      saturated with oxygen, is practically zero within the limits of experimental
      error of the microspirometer used. 2. The oxygen consumed in a microspirometer by
      the blood of patients with chronic myelogenous leucemia with a high white blood
      cell count, and of one with leucocytosis from sepsis, was proportional to the
      number of adult polymorphonuclear neutrophils in the blood. 3. No correlation
      could be made between the rate of oxygen absorption and the total number of white
      blood cells in the blood, or the total number of immature cells, or the number of
      red blood cells, or the amount of oxyhemoglobin. 4. The blood of patients with
      chronic myelogenous leucemia continued to use oxygen in the microspirometer
      longer than that of normal individuals, and the hemoglobin, in the leucemic
      bloods, became desaturated even though exposed to air. 5. In blood in which the
      bulk. of the cells were immature and the mature cells few, the oxygen consumption
      was lower than in blood in which the mature cells predominated. The rate of
      oxygen consumption of the immature cells was relatively low as compared to the
      mature. 6. The slower rate of oxygen absorption by the immature leucocytes in
      chronic myelogenous leucemia as compared to the mature cells, places them, in
      accord with Warburg's reports, in the class of the malignant tissues in this
      respect rather than in the group of young or embryonic cells.

PMID- 19869330
TI  - EFFECT OF HOST IMMUNITY TO A FILTERABLE VIRUS (VIRUS III) ON THE GROWTH AND
      MALIGNANCY OF A TRANSPLANTABLE RABBIT NEOPLASM.
AB  - Experiments are reported in which were studied the course and character of a
      transplantable malignant neoplasm in normal rabbits and in rabbits immunized with
      a filterable virus, Virus III. The disease which developed in immunized rabbits
      was extremely mild and much less severe than in normal animals. The effect upon
      the tumor process displayed by Virus III immune rabbits in the direction of
      diminished malignancy is considered to be entirely non-specific in character, and
      the suggestion is made that it is accomplished through a more effective
      resistance of the host.

PMID- 19869331
TI  - STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS : I. A METHOD FOR THE DIRECT
      OBSERVATION OF EXTRACORPOREAL THROMBUS FORMATION.
AB  - A new method has been described for the study in vivo of thrombus formation in
      blood circulating extracorporeally in an artificial loop. This method permits of
      control of many factors, and hence of intensive study of thrombus formation under
      many and varied conditions. It admits of separate study of the formation of white
      thrombi and of the deposition of fibrin, which may apparently be independent
      processes.

PMID- 19869332
TI  - EFFECT OF A FILTERABLE VIRUS (VIRUS III) ON THE GROWTH AND MALIGNANCY OF A
      TRANSPLANTABLE NEOPLASM OF THE RABBIT.
AB  - A study of a malignant disease in rabbits has been made with reference to the
      presence or absence of a filterable virus, Virus III, in the tumor. The results
      are analyzed from the standpoint of certain characteristic features of the tumor
      process in order to determine any differences in degrees of malignancy. It was
      found that a more severe disease developed in the series in which the virus
      bearing tumor was used than in the series in which the tumor was free of the
      virus, although the differences were not very marked and were not entirely
      constant. The influence of Virus III as a factor affecting malignancy has been
      discussed from the standpoint of its possible effect upon (alpha) the tumor cells
      and (b) the host reaction. It has been suggested that the greater malignancy of
      the pathological process usually induced by the virus-bearing tumor is
      attributable to a change in the response of the host to the tumor, which change
      is of the nature of a decreased resistance associated with the reaction of the
      host to the virus infection.

PMID- 19869333
TI  - FURTHER OBSERVATIONS ON THE INABILITY TO TRANSMIT A RABBIT NEOPLASM BY CELL-FREE
      MATERIALS.
AB  - It has not been possible to propagate a malignant neoplasm of the rabbit with
      cell-free filtrates, or desiccated tumor tissue or by the use of fluid media kept
      in contact with tumor tissue. These findings confirm the results of previous
      experiments carried out with early generations of the tumor. The existence of an
      agent distinct from the tumor cell which could initiate growth has not been
      demonstrated. The experiments bring out an essential biological difference
      between this mammalian neoplasm which is considered to be of epithelial origin
      and certain filtrable tumors of fowls which have been classified as sarcomata.

PMID- 19869334
TI  - ON A SPECIFIC SUBSTANCE OF THE CHOLERA VIBRIO.
AB  - The investigations described show that it is possible to extract specific
      substances from V. cholerae by means of hot dilute alcohol. This result cannot be
      attributed to the presence of bacilli in the extracts as would follow from the
      statements made by Prausnitz in his criticism of the work of Levaditi. The
      original extract contains protein and exhibits antigenic properties. From this
      preparation an almost protein-free product was obtained. It was fully active in
      the precipitin test but had lost almost completely the antigenic activity.
      Accordingly the latter preparation belongs to the class of substances described
      by Zinsser as residue antigens and studied chemically by Avery and Heidelberger.
      The fact that the immune sera resulting from the injections of the crude extracts
      acted upon the non-immunizing precipitable substance indicates that in the crude
      extract there is present an antigenic complex consisting of protein and the
      specific substance. Regarding its chemical nature it follows from the foregoing
      that the precipitable but non-immunizing substance is not a protein. On
      hydrolysis it yielded a considerable quantity of sugar although less than that
      given for the specific carbohydrates of pneumococci and B. friedlaenderi. The
      product contains nitrogen and phosphorus and on hydrolysis a substance of acid
      character separates from the solution. Accordingly the substance prepared would
      appear to have either a rather intricate structure or to be a complex
      carbohydrate, similar to those described by Avery and Heidelberger, but still
      containing impurities. This issue can probably be decided by further studies.

PMID- 19869335
TI  - STUDIES IN EXPERIMENTAL SYPHILIS : VII. REINOCULATION OF TREATED AND UNTREATED
      SYPHILITIC RABBITS WITH HETEROLOGOUS STRAINS OF TREPONEMA PALLIDUM.
AB  - Syphilitic rabbits, whether untreated or treated after the 90th day of infection,
      were found to be more refractory to subsequent inoculation with the homologous
      strain of Treponema pallidum than to inoculation with heterologous strains of the
      same organism, when clinical criteria alone were employed in judging the outcome
      of reinoculation. The incidence of second infection with homologous strains was
      5.4 per cent, as against 50 per cent with heterologous strains.(2) The resistance
      which develops in rabbits during the course of a syphilitic infection appears
      therefore to be strain-specific rather than species-specific. The protection
      afforded against homologous strains was found to persist for at least as long as
      6 months after treatment was discontinued. A given strain may afford a higher
      degree of protection against some strains than against others, but whether this
      is to be explained upon the basis of biologic relationship or of differences in
      virulence, or possibly as the result of both of these factors was not disclosed
      by the experiments. Rabbits infected with a strain (Nichols) which had been
      adapted to this species for over a decade could be infected with strains which
      had been recovered recently from the human body. The previous existence of a
      syphilitic lesion in the testis which was used as the site for reinoculation did
      not seem to exert any influence upon the incidence of successful second
      infections obtained with heterologous strains of Treponema pallidum. Sometimes
      the course of the second infection produced by inoculation with heterologous
      strains was less pronounced than that observed in the controls, but in most
      instances no significant alteration was observed. In syphilitic rabbits treated
      late in the course of the disease and reinoculated with heterologous strains of
      Treponema pallidum no lesion may develop at the site of reinoculation but
      nevertheless the Wassermann reaction may become positive and remain so for weeks
      thereafter. It is suggested that such animals may be examples of asymptomatic
      reinfection.

PMID- 19869336
TI  - STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION : VII. THE RELATION OF OPSONINS TO
      NATURAL RESISTANCE AGAINST PNEUMOCOCCUS INFECTION.
AB  - A study was made of the pneumococcidal action of serum-leucocyte mixtures of
      pneumococcus-resistant animals with a view to determining whether this property
      of the blood is to be accounted for by the presence of certain serum constituents
      or by cellular characteristics which are lacking in the blood of susceptible
      animals. By means of a method specially developed for this purpose, it was found
      that, after adequate contact with the serum of pneumococcus-resistant animals,
      virulent pneumococci were phagocyted actively not only by the homologous
      leucocytes but also by the leucocytes of other resistant and susceptible animals.
      On the other hand, pneumococci exposed to the action of the serum of pneumococcus
      susceptible animals were not taken up by the leucocytes of either the resistant
      or susceptible species. All the resistant animals tested, dog, cat, sheep, pig
      and horse, showed marked opsonic properties in their blood serum which were not
      found in the serum of susceptible ones, rabbit, guinea pig and human. There
      appeared, however, to be no essential difference in the phagocytic activity of
      the leucocytes from the various animals. It was then shown that the pneumococcus
      destroying power of serum-leucocyte mixtures was entirely abolished when heated
      serum was substituted for fresh serum and that such heated serum had lost much of
      its opsonic potency. Neither the living leucocytes alone nor extracts of the
      leucocytes were observed to exert any killing action on pneumococci. Further
      evidence of the controlling influence of opsonic action in the antipneumococcus
      defence mechanism of the blood, and its importance in natural resistance, was
      afforded by a study of the opsonin content and leucocytic functions of the blood
      of full grown and young rabbits as related to their widely varying degrees of
      pneumococcus susceptibility.

PMID- 19869337
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : VI. THE
      "REACTIVATION" OF THE BACTERIOLYTIC ACTIVITY OF OXIDIZED PNEUMOCOCCUS EXTRACTS.
AB  - The methods previously employed in the study of hemotoxins have been applied in
      the present investigation to the oxidation and reduction of the bacteriolytic
      substance of Pneumococcus. It is shown that the bacteriolytic agent, previously
      inactivated by oxidation, can be "reactivated" by treatment with bacterial
      reducing agents. Evidence is presented that this "reactivation" represents the
      reduction of inactive, reversible oxidation products to the original active
      substance. The bacteriolytic agent is an integral constituent of the pneumococcus
      cell, which can be separated from the hemotoxin by absorption with red blood
      cells in the cold.

PMID- 19869338
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : VII. THE
      DIFFERENTIATION OF TETANOLYSIN AND TETANOSPASMIN.
AB  - Tetanolysin and tetanospasmin possess in common the immunological properties of
      the group of "antitoxinogens." Both of them are contained in undeteriorated
      culture fluids of the tetanus bacillus, but each of them represents a distinct
      and separate antigenic substance. Experimental data illustrating points of
      difference in their properties are presented in this paper.

PMID- 19869339
TI  - THE EFFECT OF HEAT ON ANTIBODIES.
AB  - It is possible by means of curves to depict graphically the behavior of the
      various antibodies under various conditions. Logarithmic curves based on the data
      presented in the tables are submitted in Text-fig. 1. In general it is evident
      that antibody destruction goes on gradually as the temperature is increased. Thus
      65 degrees C. for 20 minutes diminishes the activity of all the antibodies with
      the exception of red cell agglutinin, and in this case although the final titer
      was the same evidently some of the antibody was inactivated, since the reaction
      was weaker in the higher dilutions. It can, then, be said that 65 degrees C. for
      20 minutes appreciably affects the activity of all the antibodies tested. When
      the temperature is increased to 70 degrees C. more marked differences are
      apparent. Here both types of the bacterial agglutinin and the precipitin are
      fairly stable when compared with hemolysin and red cell agglutinin. In both
      instances there is a sharp decline in the activity of the antibody. 75 degrees
      C., however, is even a more critical temperature since at this point the somatic
      bacterial agglutinin and the precipitin are completely inactivated. The hemolysin
      and hemagglutinin behave alike. The flagellar agglutinin is the most resistant of
      the group to this temperature. When the temperature is increased to 80 degrees C.
      the red cell agglutinin is completely inactivated, but sufficient hemolysin still
      remains to give a slight reaction at the lowest dilution. A further increase to
      85 degrees C. completely destroyed the hemolysin but left a definite amount of
      flagellar agglutinin; in fact, 90 degrees C. for 20 minutes did not completely
      destroy this substance, since well defined clumps in the lower serum dilutions
      could be detected on microscopic examination. In this respect, then, the
      observations of Beyer and Reagh and Orcutt that there is a well defined
      difference between the two agglutinins for the hog cholera bacillus have been
      confirmed. However, each substance tested, with perhaps two exceptions, differs
      in its behavior to heat. It is of interest to point out the similarities in the
      reaction of somatic agglutinin and precipitin. Both are diminished when heated to
      65 degrees C.; 70 degrees C. further affects the agglutinin, but not the
      precipitin; 75 degrees C. completely inactivates both. The assumption that the
      substances are apparently destroyed when they cease to react visibly with their
      respective antigens seems well founded since they cannot be reactivated with
      normal serum and no longer react to divert complement when combined in a
      hemolytic system. It might be of interest to mention briefly other experiments in
      which the temperature was kept constant and the time varied. Thus temperatures of
      50-55 degrees C. and 60 degrees C. maintained for 8 hours had no effect on
      antibody. 60 degrees C. for 4 days failed to alter materially the flagellar
      agglutinin, although the same temperature for 24 hours inactivated the somatic
      agglutinin and the cow serum precipitin. Hemolysin deteriorates slowly at 60
      degrees C., so that after 4 days the serum, which originally reacted at a
      dilution of 1:10,240, only titered 1:160. The red cell agglutinin was about as
      resistant as the hemolysin in that a little still remained at the end of the test
      period. The experiments while incomplete add further proof that the somatic
      agglutinin and the precipitin are the least resistant to heat, while the
      flagellar agglutinin is on the whole comparatively stable. A final experiment was
      performed to determine, if possible, at what temperature rabbit serum globulin
      was inactivated. With this in view, globulin was obtained by precipitation with
      ammonium sulfate, and a series of guinea pigs and chickens received several
      intraperitoneal injections. In no instance was a globulin precipitin obtained. By
      immunizing fowls in a similar manner with small quantities of rabbit serum good
      precipitin was obtained. The diluted rabbit sera heated at various temperatures
      for 20 minutes were tested for their antigenic activity with rabbit serum
      precipitin. It was found that diluted serum heated to 90 degrees C. for 20
      minutes reacted to about the same antigenic level as that not heated. Even
      boiling for 20 minutes failed to reduce greatly its antigenic properties.
      Paradoxically the visibility of the reaction was more intense with the antigen
      heated at the higher temperatures. The phenomenon was altogether so opposed to
      the usual conceptions of the inactivation of antigens that the subject will be
      gone into with more detail in a later communication. Although it is not possible
      to show definitely in the experiments that the globulin is or is not inactivated
      at certain temperatures, nevertheless it appears probable that certain of the
      antibodies are destroyed at temperatures below that capable of greatly altering
      globulin. It must be recognized that comparisons cannot be made between similar
      antibodies in the serum of different species, since somatic agglutinin in rabbit
      serum resisted 70 degrees C. for 20 minutes, although the same agglutinin in cow
      serum was destroyed at 65 degrees C.

PMID- 19869340
TI  - AGGLUTINATION BY PRECIPITIN.
AB  - Serum (antigen) when heated at a temperature sufficient to cause definite
      clouding reacts more intensely with a specific precipitin than a portion of the
      unheated serum or samples heated at lower temperatures. The phenomenon is
      explained on the basis that coagulated protein in suspension is covered with
      undenatured antigen and the addition of precipitin causes agglutination of the
      coagulated protein. Similar phenomena are obtained when bacteria or collodion
      particles are mixed with diluted serum (antigen) and precipitin added; the
      particles or bacteria agglutinate and increase the visibility of the reaction.
      Further, it is shown that collodion particles sensitized with cow serum or
      crystallized egg albumin and subsequently washed until the washing fluid no
      longer contains the antigenic substance will agglutinate when small quantities of
      specific precipitin are added. Bacteria sensitized with cow serum and
      subsequently washed until cow serum no longer remains in the washing solution
      agglutinate when cow antiserum at fairly low concentration is added. It was not
      possible to show that bacteria soaked in crystallized egg albumin and
      subsequently washed retained on their surfaces sufficient undenatured egg albumin
      to react to crystallized egg albumin precipitin.

PMID- 19869341
TI  - LOCAL PROGRESSION WITH SPONTANEOUS REGRESSION OF TUBERCULOSIS IN THE BONE MARROW
      OF RABBITS, CORRELATED WITH A TRANSITORY ANEMIA AND LEUCOPENIA AFTER INTRAVENOUS
      INOCULATION.
AB  - In this series of rabbits it was found that the rabbits dying during the 1st
      month after an injection of I or 2 mg. of bovine tubercle bacilli show the same
      conditions: extreme tuberculosis of the lungs, acute splenic tumor with
      tuberculosis, involvement of the lymph glands, an occasional small tubercle in
      the liver and extensive tuberculosis of the bone marrow. The peripheral blood has
      shown a sharp fall in the platelet count, an anemia and a fall in the
      granulocytic strain of white cells, and these changes have been correlated with
      the condition of the bone marrow. There has also been a rise in monocytes and a
      fall in lymphocytes, to a reversal of the normal ratio. When the rabbits have
      survived the first acute phase of the disease longer than 3 to 4 weeks, there
      have been signs in the peripheral blood of a recovery of the bone marrow; the
      first indication of this has been an increase in platelets, then a rise in
      hemoglobin followed in 1 or 2 days by a rise in red cells and later a return of
      the three strains of granulocytes. The bone marrow has shown a rapid spontaneous
      disintegration of the epithelioid cells correlated with the appearance of
      increased evidence of acid-fast debris in clasmatocytes, especially clear in
      those that lie along the vessels. The animals that have survived into the 3rd
      month have all shown a hyperplastic phase of the healing marrow, both the red
      cells and all types of the granulocytes appearing in the peripheral blood in
      numbers above the normal. The epithelioid cells originally containing many
      bacilli all disappear from the marrow and the only sign left, possibly suggestive
      of the tuberculosis, is the acid-fast granules in the clasmatocytes. Finally, the
      marrow becomes entirely normal, giving the normal number of red cells and
      granulocytes to the blood. Thus, bone marrow in the rabbit has become involved in
      every instance with the injection of massive doses of viable bacilli. The
      findings at autopsy in those animals followed during the early reaction to
      infection confirm this directly and, since the curves of the cells in the
      peripheral blood of the more chronic animals were the same during the early
      stages of the disease as in those that died, the same conclusion seems justified
      from indirect inference for them. The method of healing has been a rapid
      disintegration of the epithelioid cells without caseation. The bone marrow heals
      itself entirely regardless of the progress of the disease elsewhere, so that one
      sees the remarkable condition of an animal recovering from the anemia and
      leucopenia while dying of tuberculosis elsewhere. The spleen also shows a
      tendency toward spontaneous healing. In the animals that have lived beyond 100
      days there has been some gradual lessening of the diffuse distribution and extent
      of pulmonary lesions with the development of cavitation together with a marked
      involvement of the kidneys and lesions in the eyes.

PMID- 19869342
TI  - STUDIES ON IMMUNITY TO PNEUMOCOCCUS MUCOSUS (TYPE III) : III. INCREASED
      RESISTANCE TO TYPE III INFECTION INDUCED IN RABBITS BY IMMUNIZATION WITH R AND S
      FORMS OF PNEUMOCOCCUS.
AB  - 1. Immunization of rabbits with Type III pneumococci is effective in producing
      active immunity against infection with a virulent strain of the homologous
      organism. 2. Immunization of rabbits with Type I or II pneumococci, and with R
      forms derived from any of the fixed types, is equally effective in producing
      active immunity against Type III infection. 3. Immunization of rabbits with
      nucleoprotein or with desoxycholate solutions of heterologous pneumococci, under
      the experimental conditions described, appears to be ineffective in producing
      active immunity against Type III infection.

PMID- 19869343
TI  - STUDIES IN ULTRAFILTRATION.
AB  - We are submitting this series of experiments as observed facts, realizing that
      there are so many uncertainties in this form of indirect observation that great
      caution must be exercised in drawing conclusions of any kind. The most serious of
      the possible errors involved is that the active substances which we have studied,
      the enzyme-the bacteriophage-and the several varieties of virus, may not be free
      in our suspensions, but are adsorbed to larger particles. The peculiar
      difficulties encountered in filtering herpes virus particularly suggest a source
      of error of this kind, and if we are right in assuming the intracellular position
      of this virus in the nervous tissue, it is more than likely that most of the
      virus obtained in suspension may be closely associated with protein particles
      derived from the cells. Keeping all this in mind, we may, nevertheless, derive a
      certain amount of information from our experiments as follows: 1. The order of
      magnitudes of the pure proteins with which we have worked,-namely, crystallized
      egg albumen, crystallized serum albumen and purified casein,-follows the order of
      molecular weights of these substances as determined by Cohn. As far as casein is
      concerned, the size indicated by filtration in comparison with collargol is far
      greater than it should be by calculations which take a molecular weight of
      192,000 as the point of departure. While one cannot be sure of the reason for
      this, there are many possible explanations such as considerable swelling of the
      casein partides, aggregation of molecules and the fact that casein is not at its
      isoelectric point under the conditions of filtration and surely present as a
      salt. 2. Trypsin, even in the certainly very impure condition in which we
      employed it, is but very slightly larger than serum albumen and distinctly
      smaller than casein. In its pure form it may well be much smaller even than our
      filtrations indicate, but certainly not larger. This relatively small size of
      trypsin may have considerable bearing upon the question of whether or not the
      lytic agents spoken of as "bacteriophage" are substances of the nature of
      enzymes, or whether they are more comparable to the filtrable virus, as supposed
      by d'Herelle. 3. Herpes virus, the Rous chicken sarcoma and a staphylococcus
      bacteriophage were all subjected to filtration at pH 7.2 and at hydrogen ion
      concentrations higher than 8, which is given by Olitsky and Boez as the
      isoelectric point of foot-and-mouth disease, but failed to pass membranes which,
      at the same pressures, were permeable for casein and collargol. The bacteriophage
      and the Rous sarcoma with considerable regularity passed through membranes which
      held back colloidal arsenic trisulfide. We have cited only a few of the
      experiments which were actually done, every one of the tests tabulated being
      merely representative of a number of others that were omitted for economy of
      space. The herpes virus we have had greater difficulty in filtering. We cite one
      experiment with a 2 per cent acetic-collodion membrane and another with a 1.5 per
      cent membrane through which the herpes virus passed, the membrane being so
      controlled that gross leakage could be excluded. We believe that the difficulty
      here is very largely due to the fact that in preparing the herpes virus for
      filtration it cannot be separated from considerable amounts of brain material,
      from which, perhaps, it is not easily dissociated. This would be natural if the
      herpes virus were intracellularly located, as we believe it to be. This
      experiment and similar ones, however, incline us to believe that the herpes virus
      is not far different from the Rous sarcoma virus and the bacteriophage, as far as
      filtration through membranes is concerned. It certainly is not smaller than
      either of these substances and probably, as we judge from a few experiments
      carried out at higher pressures, is not much larger. It may be assumed,
      therefore, that in the form in which we were able to procure the bacteriophage
      and the two varieties of virus investigated by us, they were of a magnitude
      larger than casein and collargol and smaller than colloidal arsenic. The weak
      point in drawing our conclusions is the fact that we were not in a position to
      measure for ourselves with any accuracy the actual sizes of collargol and arsenic
      trisulfide particles. Accepting the general views of Bechhold and others,
      however, our experiments would define the sizes of the separticular substances as
      larger than 20 mmicro and probably smaller than 100 mmicro. The order of
      magnitudes of the substances measured by us would then be as follows:
      Crystallized egg albumen Crystallized serum albumen Trypsin Collargol Casein
      Bacteriophage, Rous sarcoma virus, herpes virus Arsenic trisulfide Our
      experiments show little agreement with the work of Levaditi and Nicolau and of
      Levaditi, Nicolau and Galloway. In their recent filtration tests of foot-and
      mouth disease this virus is reported by them as passing through membranes that
      held back trypsin, indicating a size much smaller than any of the viruses
      measured by us. Our results, on the other hand, are in actual measurements
      comparable to those of Olitsky and Boez, not only in the fact that the viruses
      with which we worked correspond approximately to the size determined by them for
      foot-and-mouth disease, but that the percentage of collodion in membranes
      permeable for virus and impermeable for colloidal arsenic corresponds almost
      exactly to our own. This gives us confidence that the technique developed may be
      more easily standardized than we at first believed and that the method of
      ultrafiltration, owing to the great ease with which membranes of relatively
      standard size may be made, may have valuable applications in the investigation of
      bacteriological and immunological problems.

PMID- 19869344
TI  - NATURE OF THE TOXIC MOIETY OF STREPTOCOCCUS SCARLATINAE.
AB  - The cutaneous reaction demonstrates that the culture lysate of Streptococcus
      scarlatinae is approximately ten time more potent in its toxic effect than is the
      culture filtrate since repeated and carefully controlled human skin tests show
      that 0.1 cc. of a 1:2000 dilution of lysate reacts equally as well as a similar
      dose of a 1:250 dilution of culture filtrate (Dick's standard skin unit). Animal
      tests and the human intradermal reaction clearly reveal that the toxic principle
      of culture filtrate (Dick's toxin) and culture lysate (Duval-Hibbard endotoxin)
      are of the same nature) namely intracellular derivatives of the streptococcal
      cell. The in vivo prepared lysate affords a more potent antigen for the
      production of an antiendotoxic serum than the living, killed or culture filtrate
      of Streptococcus scarlatinae. The inoculations into dogs of culture filtrate and
      of the "washed coccal bodies" yield strikingly different results. In those that
      receive filtrate no toxic effect is produced while in the ones injected with the
      washed coccal bodies a severe and often fatal toxemia results. The dog is highly
      susceptible to infection with Streptococcus scarlatinae and also readily affected
      by injections of the in vivo prepared lysate. Toxic effects are produced almost
      immediately following the intravenous injection of lysate and death usually
      occurs in 24 to 48 hours from an acute hemorrhagic nephritis. Daily urinary
      examination shows a high percentage of albumin, large numbers of fine granular
      casts and quantities of macroscopic blood. A study of the kidney sections reveals
      an extensive glomerulonephritis. The work reported constitutes further evidence
      in support of our original contention that the poisonous substance of the
      scarlatinal streptococcus is derived from the bacterial cell set free through the
      dissolution of the germ plasm. The liberation of the poison in vitro occurs as
      the natural result of autolysis while in vivo it is produced through specific
      action of bacteriolysin.

PMID- 19869345
TI  - LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS : I. EXPERIMENTAL
      PNEUMOCOCCAL MENINGITIS IN RABBITS.
AB  - 1. Fatal Type I pneumococcal meningitis may be produced in rabbits by
      intracisternal injection of pneumococci. 2. When organisms are of high virulence,
      the rabbit does not tend to localize them in the meninges, but an early
      septicemic process results. Death is septicemic rather than meningeal. 3. In such
      instances very little cellular reaction occurs in the meninges. 4. Active or
      passive immunization previous to intracisternal infection inhibits partially the
      septicemia and permits the development of reactional processes in the meninges.
      5. The immunization likewise retards the meningeal disease, but multiplicity of
      factors prevents us from stating precisely to what this retardation is due. It is
      not correlated with the presence of agglutinins in the spinal fluid at the time
      of infection. 6. The rapidity of production of meningitis is influenced by the
      phase of growth of the culture used, and likewise by the growth activity of that
      culture. 7. To some extent in the partially immune rabbit the meningeal spaces
      constitute a relatively non-immune reservoir, constantly feeding the blood stream
      and breaking down systemic resistance. 8. Intrathecal serum treatment causes
      rapid agglutination and phagocytosis of pneumococci, and has very rarely,
      possibly, resulted in cure. Essentially no phagocytosis occurs in the absence of
      immune serum. 9. Phagocyted pneumococci stained supravitally take up the neutral
      red stain and are therefore probably injured. 10. The treatment employed
      subsequent to infection only slightly prolongs life in the majority of cases. It
      does retard septicemia. 11. The treatment improves the cellular reactional
      processes in the meninges. 12. A study of the pathology of rabbit pneumococcal
      meningitis shows that the location of pneumococci precludes complete contact with
      serum introduced intrathecally, and that these locations provide isolated foci,
      from which organisms may reinfect the meningeal spaces as rapidly as they are
      removed by lavage or antibody injections. 13. In recovered rabbits postmeningeal
      symptoms, weakness, ataxia, nystagmus, and paralyses arise. 14. In our opinion
      there is some objective evidence of benefit of serum therapy. The rabbit is too
      susceptible, however, and conditions too artificial to admit of definite
      conclusions. 15. Rough Type I pneumococci introduced in large quantity
      cisternally may kill and may be recovered 24 hours after infection, from spinal
      fluids. In a series of eleven passages, no reversion to smooth type occurred. In
      all animals injected with rough forms, transient bacteremia resulted.

PMID- 19869346
TI  - LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS : II. THE
      PRODUCTION, PATHOLOGY, AND TREATMENT OF TYPE I PNEUMOCOCCAL MENINGITIS IN DOGS.
AB  - 1. Extensive acute, fibrinopurulent meningitis may be produced in dogs by the
      intracisternal injection of virulent Type I pneumococci. 2. Given an equal number
      of virulent infecting organisms, the rate of establishment of infection depends
      upon the phase of growth and the quantitative growth per cc. of culture plus an
      uncontrollable individual factor in the animal. 3. The pathology of pneumococcal
      meningitis is discussed. It resembles very closely the similar disease in man. 4.
      Systematic lavage and treatment with optochin-serum mixtures by the method of
      quadruple puncture, as described above, have resulted in cures of Type I
      pneumococcal meningitis in dogs. 5. The important factor in obtaining cures is to
      bring all regions of the meninges into frequent contact with the therapeutic
      agent. 6. In the absence of such contact, incomplete sterilization results and
      "reinfection" is almost inevitable. 7. Protocols show the necessity of repeated
      negative cisternal fluids, both on smear and on culture, before sterilization can
      be assured. 8. Recovered dogs subjected to meningeal reinfection show some degree
      of resistance.

PMID- 19869347
TI  - ENLARGEMENT OF THE ADRENAL CORTEX IN EXPERIMENTAL UREMIA.
AB  - The production of an experimental uremia in the albino rat by removal of both
      kidneys is followed by hypertrophy of the adrenal glands. In the case of male
      rats 90 days of age this adrenal enlargement amounted to 65 per cent and in the
      case of female rats 180 days of age 47 per cent. The increase in the size of the
      whole gland is due entirely to hypertrophy of the cortex. This increase in the
      volume of cortical tissue amounted to approximately 40 per cent for males and 61
      per cent for females and was due in large part to an increase in the size of the
      cells. The content of water and material soluble in fat solvents was higher in
      the uremic than the control glands. However after subtraction of such storage
      materials a true hypertrophy of the cortex still remained. It amounted to 21 per
      cent. Histologically the stainable fat had a more irregular distribution and was
      present in lesser amount in the adrenals from the uremic animals. The capillaries
      of the medulla and reticular cortex were distended. The nuclei of both the
      cortical and medullary cells were swollen and stained faintly.

PMID- 19869348
TI  - THE SYSTOLIC BLOOD PRESSURE OF THE NORMAL RABBIT MEASURED BY A SLIGHTLY MODIFIED
      VAN LEERSUM METHOD : FINAL REPORT.
AB  - The blood pressure and pulse rate of 90 normal rabbits have been studied for
      various periods of time, from 1 day (accidental death interrupting the
      observation) to 15 months. The main data are presented in a table containing the
      blood pressure and pulse rate on the 1st day of observation, the maximum and
      minimum of both during the entire period of observation of each animal, together
      with the sex and weight of the animal. Separate tables are given showing the
      distribution of blood pressure, pulse rate and the "maximum" blood pressure by
      animals. Detailed data on two animals observed for the longest time are given in
      tabular form. The anatomical changes that occur in some carotids enclosed in a
      loop are described and discussed. Considerations on "excitement" and pathological
      conditions which arise spontaneously in rabbits are given. A criterion for a
      pathologically high blood pressure in rabbits is proposed. The blood pressure of
      the normal rabbit ranges between 70 and 170 mm. Hg. The pulse rate, taken
      simultaneously with the blood pressure, fluctuates between 112 and 300 per
      minute.

PMID- 19869349
TI  - EXPERIMENTAL ATHEROSCLEROSIS AND BLOOD PRESSURE IN THE RABBIT.
AB  - 1. Van Leersum's range for the normal blood pressure in the rabbit, as recorded
      by his method, is confirmed. 2. Van Leersum's conclusion concerning the influence
      of a liver diet on the blood pressure of the rabbit is not substantiated by his
      data, since the fluctuations of blood pressure he obtained do not surpass his own
      recorded figures for normal animals. 3. Fluctuations of systolic blood pressure
      beyond the "normal" range are not necessary for the production of experimental
      atherosclerosis of the aorta in rabbits. Inversely, egg yolk feeding experiments
      in rabbits in which atherosclerosis of varying degree, even extreme, is obtained,
      are not accompanied by an elevation of blood pressure outside the "normal" range.
      4. The fluctuations of blood pressure observed during experimental
      atherosclerosis do not simulate the condition of essential hypertension in man.

PMID- 19869350
TI  - STUDIES ON THE BIOLOGY OF STREPTOCOCCUS : VII. ALLERGIC REACTIONS WITH STRAINS
      FROM ERYSIPELAS.
AB  - Rabbits immunized with filtrates of cultures of hemolytic streptococcus from
      erysipelas show cutaneous allergy. Two periods of allergy have been observed, an
      early and a late phase. The earliest reactions occurring in the first period of
      allergy can be neutralized with erysipelas immune sera. The rash of scarlet fever
      and the Dick reaction are apparently allergic reactions to products of
      Streptococcus scarlatinae.

PMID- 19869351
TI  - STUDIES ON STREPTOCOCCUS BACTERIOPHAGE : I. A POWERFUL LYTIC PRINCIPLE AGAINST
      HEMOLYTIC STREPTOCOCCI OF ERYSIPELAS ORIGIN.
AB  - 1. The "sludge" phage obtained by Clark and Clark answers all requirements for
      pronouncing it identical with the classical bacteriophage. 2. The "sludge" phage
      failed to produce lysis in any of the 102 human pathogenic streptococci tested.
      3. Numerous attempts to induce regeneration of various lytic principles by human
      streptococci resulted in failure. 4. It was possible, however, to "train"
      erysipelas streptococci to regenerate a lytic principle active against 76 per
      cent of strains of this group. 5. The erysipelas phage showed remarkable
      specificity.

PMID- 19869352
TI  - THE RHYTHMIC RANGE OF THE WHITE BLOOD CELLS IN HUMAN, PATHOLOGICAL LEUCOPENIC AND
      LEUCOCYTIC STATES, WITH A STUDY OF THIRTY-TWO HUMAN BONE MARROWS.
AB  - In a study of twenty clinical cases with a wide range of diagnoses, repeated
      total counts of the white cells at 15 minute intervals reveal a large fluctuation
      at various levels comparable to that found for the normal (1, 2). The
      granulocytes seem to follow a more or less hourly rhythm, the most marked shift
      to the left in the Ameth pattern and the moment of greatest percentage of
      motility coinciding with the peaks. The independence found existing between the
      peripheral blood concentrations of individual strains of white cells and the red
      cells, as determined by total and differential counts, their differential
      response to pathological and pharmacological stimuli, and their normal relative
      relations, all indicate some separate physiological mechanism of control for each
      type of cell, either working through, or independently of, their sources of
      origin. The many factors to which the circulation of the blood, as such, is
      subject, the complexity of the influences on origin, maturation, delivery,
      longevity, and destruction of each cell group, the limitations inherent in the
      present involved, indirect technics of counting, combine to make any single
      observation subject to grave misinterpretation. The value to the clinician must
      come in repeated observations, at times when the diagnosis or a therapeutic
      procedure is in doubt, at frequent intervals, at other times over longer or
      shorter periods, but always with the relation between consecutive counts, rather
      than the absolute values, the important point for consideration. Both the red and
      the white cells probably change their relative concentrations in the peripheral
      blood from time to time over a considerable range that is quite within normal
      physiological limits, so that, in theoretical considerations and in practical
      functional estimations, a zonal concept with adequate individual extremes should
      always be kept in mind for both physiological and pathological states. A
      cytological analysis of thirty-two bone marrows from human biopsy and autopsy
      material shows the striking reciprocity found to exist between the myelocytes and
      the mature polymorphonuclear leucocytes. This, together with the observed focal
      uniformity of maturation found in bone marrow, and the periodicity of the
      fluctuations of the neutrophils in the peripheral blood, leads to the formulation
      of the hypothesis of a constant functional withdrawal of granulocytes from the
      peripheral blood with a periodic delivery of new cells from the marrow, which in
      leucopenia and in leucocytosis represents a depression or a stimulation,
      respectively, of the normal mechanism. The nature and degree of the response are
      an approximate index of the cellular factor in the complex of the "resistance" of
      the particular individual.

PMID- 19869353
TI  - STUDIES ON A PARATYPHOID INFECTION IN GUINEA PIGS : III. A SECOND TYPE OF
      SALMONELLA NATURALLY APPEARING IN THE ENDEMIC STAGE.
AB  - The spontaneous appearance of a second paratyphoid infection in a guinea pig
      population during the endemic stage of an earlier epidemic is reported. A
      comparative study of the gross pathology of the two infections indicated a
      difference in the loci of development of the respective organisms in the animal
      host. The two types were readily differentiated by direct agglutination with
      specific immune serums. From its agglutinative affinities the second organism was
      judged to be an aertrycke type of B. paratyphi.

PMID- 19869354
TI  - VARIATIONS IN THE SCOURS TYPE OF BACILLUS COLI FROM THE STANDPOINT OF
      BACTERIOPHAGIC ACTION.
AB  - 1. A lytic agent was not demonstrable in culture filtrates of either the parent
      or variant type of the scours organism. 2. The parent type was resistant to the
      action of a "weak" bacteriophage, obtained from the animal host, while the
      variant type was susceptible. 3. Exposure of the variant type to the scours
      bacteriophage was attended by agglutination of the cells, marked swelling, and an
      alteration of the contents prior to lysis. 4. The manifestations of variation
      which regularly occur on agar plate cultures of the scours organism do not appear
      to be the result of bacteriophagic stimulation.

PMID- 19869355
TI  - MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION
      OF WHITE MICE : XII. THE EFFECT OF DIET ON HOST RESISTANCE. FURTHER STUDIES.
AB  - When 5 per cent of butter fat or cod liver oil is added to a bread and milk diet,
      in itself adequate to promote the breeding and rearing of a healthy stock of mice
      through a period of years, the resistance of these mice to per os infection with
      the paratyphoid mouse typhoid bacillus (B. pestis caviae), as compared to that of
      mice on the unmodified diet, is definitely increased. A similar effect may be
      obtained with a McCollum "complete" diet, even when the butter fat is omitted,
      and with a bread and milk diet in which the milk used has been rayed with a
      mercury vapor lamp. When an inactive fat like Crisco is added to the bread and
      milk diet, the results obtained are not very clear-cut. While seasonal
      fluctuations in resistance to mouse typhoid were not completely eliminated by the
      various modified diets, they were nevertheless reduced, the modified diets
      tending to stabilize the death rate at a point lower than that usually reached by
      the mice on the control diet.

PMID- 19869356
TI  - AN EXPERIMENTAL STUDY OF DIATHERMY : I. THE MEASUREMENT OF LUNG TEMPERATURE.
AB  - 1. Experimental evidence is furnished to show that in normal animals the rectal
      temperature can be elevated by the passage of high frequency currents. 2. During
      life the intraabdominal and intrathoracic temperatures can be increased only
      slightly above the rectal temperature. 3. The lung temperature in the
      anesthetized dog normally lies 0.3-0.4 degrees C. below the rectal temperature.
      During the passage of diathermy currents of strengths equivalent to those used in
      therapy this relationship is reversed-the lung temperature exceeding the rectal
      temperature by about the same value. 4. Immediately after death, the temperature
      rises abruptly in the deep tissues between the electrodes. 5. For the measurement
      of deep temperature special thermocouples have been devised. Their method of
      preparation and mode of use are described.

PMID- 19869357
TI  - AN EXPERIMENTAL STUDY OF DIATHERMY : II. THE CONDITIONS NECESSARY FOR THE
      PRODUCTION OF LOCAL HEAT IN THE LUNGS.
AB  - 1. Prevention of the access of air to one lung, while its circulation is intact,
      results in little, if any, change in the rate of heating of the lung by the
      diathermy current. 2. Occlusion of a main branch of the pulmonary artery during
      the flow of the current results in a sudden rise in temperature in the lung whose
      artery has been occluded, with subsequent heating, however, at the original rate.
      Under these circumstances death of the animal is accompanied by a precipitous
      rise in the temperature of both lungs. 3. When the pulmonary veins as well as the
      artery to one lung are ligated the circulation through the bronchial vessels is
      also stopped. Diathermy then results in a local rise in temperature in the lung
      equivalent to that seen in the other lung after death.

PMID- 19869358
TI  - AN EXPERIMENTAL STUDY OF DIATHERMY : III. THE TEMPERATURE OF THE CIRCULATING
      BLOOD.
AB  - 1. A method of measuring intravascular temperatures in anesthetized dogs has been
      described. 2. The temperature in the abdominal aorta is uniform throughout, and
      varies only with the systemic temperature. 3. The temperature in the inferior
      vena cava rises as the thermo-couple approaches the heart, reaching its maximum
      at about the level of the hepatic veins. Between the hepatic veins and the right
      chambers of the heart there is no further elevation in venous temperature. 4. The
      temperature of the right heart blood normally exceeds that of the left heart
      blood by 0.05-0.2 degrees C. 5. During the application of high frequency currents
      to the thorax, this relationship is reversed. 6. This indicates that the lungs
      are being heated but that the blood passing through the pulmonary vessels is
      removing the heat at approximately the rate of production.

PMID- 19869359
TI  - THE SOLUBLE SPECIFIC SUBSTANCE OF FRIEDLANDER'S BACILLUS : III. ON THE ISOLATION
      AND PROPERTIES OF THE SPECIFIC CARBOHYDRATES FROM TYPES A AND C FRIEDLANDER
      BACILLUS.
AB  - 1. Methods are given for the isolation of specifically reacting nitrogen-free
      polysaccharides from Type A and Type C Friedlander's bacillus. 2. The properties
      of these specific carbohydrates have been outlined.

PMID- 19869360
TI  - THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : IV. THE ACTION OF
      DIPHTHERIA TOXIN IN SPLENECTOMIZED AND BLOCKED MICE.
AB  - 1. The minimum amount of diphtheria toxin which killed normal mice of from 24 to
      30 gm. in weight upon intravenous injection, was found to be between 75 and 100
      times the M.F.D. for the guinea pig. When given intraperitoneally, the fatal dose
      for mice was as high as 200 M.F.D. 2. There was no significant difference in the
      lethal action of diphtheria toxin for normal mice and mice in which an
      elimination of the reticulo-endothelial system had been attempted by means of
      blocking injections of India ink, or splenectomy, or a combination of both
      operations. 3. Attempts to infect normal mice and mice treated as described with
      large doses of a highly virulent diphtheria strain were unsuccessful with both
      groups of animals.

PMID- 19869361
TI  - A STUDY OF THE PERIVASCULAR TISSUES OF THE CENTRAL NERVOUS SYSTEM, WITH THE
      SUPRAVITAL TECHNIQUE.
AB  - 1. The presence of clasmatocytes in the adventitial sheath of the blood vessels
      of the normal brain has been shown. Thus far, these are the only mesodermal
      phagocytes, the presence of which in the central nervous system has proven to be
      demonstrable by the supravital technique. 2. The clasmatocytes are vacuolated
      even normally. 3. The vacuolation increases in the clasmatocytes of the whole
      brain as result of a localized injury, and it increases also throughout the
      central nervous system in the early stages of an herpetic encephalitis, even
      before gross damage to nerve cells or myelin can be demonstrated. 4. The
      endothelial cells of blood vessels have not exhibited any signs of multiplication
      or of vacuolation. They have not apparently given rise to any of these
      phagocytes, nor taken any part in the phagocytic reaction themselves. 5. Along
      capillaries, the phagocytic cells are seen only rarely, and it is possible that
      they have wandered along these vessels from the nearby venules and arterioles. 6.
      Trypan blue, injected without pressure into the subarachnoid space, finds its way
      rapidly down the perivascular sheath and enters the clasmatocytes of the sheath,
      deep within the substance of the brain. From this fact may be deduced the
      functional patency of the perivascular channels and their continuity with the
      subarachnoid space. 7. Lymphocytes are seen normally in the perivascular sheath,
      and the presence of the large young forms along with the intermediate and the
      small old cells suggests that they develop in this situation and give rise to the
      lymphocytes of the cerebrospinal fluid by wandering out into the subarachnoid
      space. 8. In response to an herpetic encephalitis, as well as other injury, a
      huge increase in the number of lymphocytes and of clasmatocytes occurs in the
      perivascular tissues. 9. The multiplication of both cell types seems to begin
      simultaneously, but never at the same spot, any one point along a vessel
      exhibiting a marked preponderance of either one form or the other. 10. The
      resting clasmatocytes cannot readily be differentiated from any other fusiform
      cell in sections of fixed tissues; while the lymphocyte may appear, in such
      sections, as an apparently isolated small round mononuclear cell, with no visible
      relation to the perivascular apparatus.

PMID- 19869362
TI  - THE RELATION OF MONOCYTES AND CLASMATOCYTES TO EARLY INFECTION IN RABBITS WITH
      BOVINE TUBERCLE BACILLI.
AB  - 1. The early reaction to intravenous tubercular infection in the various organs
      of the rabbit reveals a pathognomonic response in the lungs within 24 hours; the
      specific response in the liver, spleen, lymph glands, and bone marrow, follows
      from the 6th to the 14th days. 2. The development and extent of the pathologic
      process has been analyzed in terms of the activity of monocytes and
      clasmatocytes. 3. The criteria for differentiating these mononuclear phagocytic
      cells into two strains have been analyzed and the technics discussed. 4. The
      clasmatocyte phagocytizes tubercle bacilli freely and fragments them, as it does
      all cellular and other debris. 5. The monocyte stimulated to metamorphose into
      the typical epithelioid and giant cell of the Langhans type retains the tubercle
      bacilli intact, with power to survive and multiply, over long periods of time. 6.
      The normal number of monocytes or the degree to which monoblasts may be
      stimulated to development and maturation, together with the activity of the
      clasmatocytes in destroying bacilli, in any particular region, would appear to be
      a function of the rapidity and extent of the local tubercular involvement.

PMID- 19869363
TI  - THE BIOLOGICAL REACTIONS IN RABBITS TO THE PROTEIN AND PHOSPHATIDE FRACTIONS FROM
      THE CHEMICAL ANALYSIS OF HUMAN TUBERCLE BACILLI.
AB  - 1. The clasmatocyte, the cell with the power of fragmenting tubercle bacilli, the
      cell making the lesion of the so called interstitial pneumonia, has been shown to
      be the overwhelming response to the special protein fractions, 304 and 903.
      Multiple hemorrhages, high fever, and toxicity have marked the use of these
      fractions in every instance. 2. The epithelioid and the giant cell of the
      Langhans type, making typical tubercular tissue, have been the massive and
      specific response of the peritoneal cavity to intraperitoneal injections of the
      phosphatide fractions, A-3 and A-4. These fractions have been entirely non-toxic
      in the dosages used.

PMID- 19869364
TI  - THE EFFECT OF SERUM UPON THE GERMICIDAL ACTION OF SOAPS.
AB  - 1. Far more information about the effect of serum or other substances upon the
      germicidal action of soaps can be obtained by determining the germicidal titers
      over a wide range of pH than by determining the titer at a single pH. In this way
      a characteristic curve for each test substance is obtained. 2. The curve for a
      particular concentration of serum bears a definite relationship to the curve for
      salt solution (buffer) alone. Wherever the titer in salt solution is high, very
      small amounts of serum greatly diminish that titer. Wherever the titer in salt
      solution is low, small amounts of serum leave the titer unchanged. Thus small
      additions of serum flatten the curves and make them more nearly horizontal. If
      further large amounts of serum are added, a further reduction in titer takes
      place at all reactions. 3. The calcium of serum has only a very slight effect
      upon the soap titer. 4. The protein of serum is probably inhibitory to soaps; but
      the curve for partially defatted serum, and the curves for other protein
      substances tested, do not run parallel to the serum-soap curves. 5. The various
      lipoids that are known to be present in serum are inhibitory to the action of
      soaps, both as emulsions and as clear solutions. 6. The action of serum upon
      soaps may be regarded as a complex reaction, in which lipoids, protein, and, to a
      lesser extent, calcium salts take part. Their effect is due to the fact that
      these substances, by combining with the soaps, remove them from the field of
      germicidal action.

PMID- 19869365
TI  - THE INFLUENCE OF PROTEIN-FREE LIVER AND SPLEEN EXTRACTS ON THE BLOOD REGENERATION
      AND RESPIRATORY EXCHANGE OF ANEMIC RABBITS.
AB  - 1. Respiratory exchange measurements may be used for gaining further evidence
      concerning the body changes during anemia, and are complementary to the
      hematological and histological data. 2. The heat production during anemia was
      slightly decreased. At the 3rd week it began to rise. 3. A protein-free liver
      extract has accelerated blood regeneration and at the same time increased the
      respiratory exchange of anemic animals. 4. A protein-free spleen extract has
      distinctly lowered the respiratory exchange of normal animals. The metabolism of
      anemic animals thus treated was practically the same as before bleeding and
      treatment. The recovery of the spleen extract-treated animals was not complete
      during the period of observation. This extract may have been somewhat toxic. In
      spite of this disturbing factor we are not inclined to accept the view of C. D.
      and E. W. Leake (15) and Thalhimer (16) that the spleen takes part in the
      stimulating effect upon blood regeneration when given in combination with red
      bone marrow by mouth.

PMID- 19869366
TI  - VITAMIN A DEFICIENCY AND METAPLASIA.
AB  - Of nineteen rats on a complete diet (Group III, Diet + C. L. O.), none showed
      foci of squamous keratinizing epithelium in abnormal situations. Of twenty-six
      rats on a diet deficient in vitamins A and D (Group I, Diet-A-D), twenty-three
      showed metaplastic changes of varying degree in one or more organs; the
      metaplasia was of columnar, cuboidal, and transitional epithelium to the squamous
      keratinizing type. Of eighteen rats on a diet deficient in vitamin A alone (Group
      II, Diet-A), seventeen showed epithelial metaplasia similar to that of Group I in
      one or more organs. In Groups I (Diet-A-D) and II (Diet-A) the changes occurred
      in one or more of the following organs: trachea, large bronchi, small bronchi or
      bronchioles in lung, posterior nares, accessory salivary glands of base of
      tongue, paraocular, submaxillary, sublingual, and parotid glands, renal pelvis,
      ureter, and bladder. The metaplastic changes were as extensive in the rats of
      Group II on a diet deficient in vitamin A alone as in those of Group I which
      received a diet deficient in vitamins A and D.

PMID- 19869367
TI  - THE OXYGEN CONTENT OF THE VENOUS BLOOD OF THE DOG AFTER UPPER GASTROINTESTINAL
      TRACT OBSTRUCTION.
AB  - There is a rapid fall in the oxygen content of the venous blood of the dog after
      upper gastrointestinal tract obstruction. This increased deoxidation is probably
      due to a combination of several factors. There is much evidence to suggest that
      active reducing bodies are present in the blood.

PMID- 19869368
TI  - AN EXPERIMENTAL STUDY OF DIATHERMY : IV. EVIDENCE FOR THE PENETRATION OF HIGH
      FREQUENCY CURRENTS THROUGH THE LIVING BODY.
AB  - The principles governing the passage of high frequency currents through various
      conductors have been discussed and exemplified in experiments done on both non
      living and living bodies. In Part I it was shown: (1) That the current takes the
      path of least electrical resistance rather than the shortest path; (2) that
      maximal heating occurs at the point of greatest concentration of the lines of
      current flow. In a homogeneous medium with parallel electrodes maximal heat
      production occurs in those portions of the medium adjoining the electrodes and
      the heat gradient is from without inward. Under these circumstances maximal
      heating never occurs at the center. In discussing the localization of heat not
      only the electrical resistance and current concentration, but also the cooling
      effect, must be considered. In experiments on the dog's cadaver no evidence of
      the so called "skin effect" could be demonstrated. This is in contradistinction
      to the findings of Bettman and Crohn, but the discrepancy is explained on the
      basis of what we believe to be a technical error in their work. The finding of no
      "skin effect" is in agreement with the conclusions of Dowse and Iredell, based on
      both experimental and theoretical considerations. In Part II three types of
      experiments were performed on the anesthetized dog. The conclusions to be derived
      from them are these: (1) The heat gradient of the body is reversed during
      diathermy and heating occurs from without inward; (2) deep heating during
      diathermy is greater than that which results from the application of local heat
      to the skin; (3) the lung can be heated by diathermy in spite of simultaneous
      cooling of the chest wall. These experiments we regard as satisfactory evidence
      of the passage of the current through the interior of the body.

PMID- 19869369
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : VIII. THE
      ANTIGENIC PROPERTIES OF HEMOLYTICALLY ACTIVE AND HEMOLYTICALLY INACTIVE
      MODIFICATIONS OF PNEUMOCOCCUS HEMOTOXIN.
AB  - THE FOLLOWING MODIFICATIONS OF THE ANTIGEN (PNEUMOCOCCUS HEMOTOXIN) WERE STUDIED:
      (1) the hemolytically active (reduced) substance; (2) the hemolytically inactive,
      reversible oxidation product; (3) the inactive irreversible products formed by
      treatment With high concentrations of H(2)O(2); (4) the inactive products formed
      by heat. The antibody-invoking property of the reversibly oxidized form seemed to
      be identical with that of the original, hemolytically active or reduced form;
      neither of the other two hemolytically inactive products invoked antibody
      production. The same modifications of the antigen which exhibited the antibody
      invoking property in vivo possessed the antibody-combining property in vitro; and
      the modifications which lacked the one property also lacked the other. Evidence
      is presented that the groups of the hemotoxin molecule in which the true
      antigenic properties are resident are not necessarily altered by processes which
      inactivate the groupings responsible for the toxic (hemolytic) action of the
      original antigen. The lack of antigenic properties on the part of the other two
      hemolytically inactive modifications is evidence that the treatment employed to
      alter the toxic property of the molecule must be properly chosen to avoid
      profound changes which affect the antigenically effective groupings. From an
      immunological point of view, the reversibility of the antigenically effective
      oxidation product of pneumococcus hemotoxin is important as an index that the
      loss of toxicity (hemolysis) was accomplished without a profound change in the
      molecule. The theoretical significance of the antigenicity of non-toxic
      modifications of toxic antigens is discussed.

PMID- 19869370
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : IX. THE
      ERYTHROCYTE-COMBINING PROPERTY OF PNEUMOCOCCUS HEMOTOXIN.
AB  - The investigation dealt particularly with the combination of pneumococcus
      hemotoxin with red blood cells. The reduced or hemolytically active form of the
      hemotoxin was known to possess the property of erythrocyte combination. The
      results obtained in this study indicate that the hemolytically inactive,
      reversibly oxidized form exists in two different modifications; one retains the
      property of erythrocyte combination while the other lacks this property. The
      influence of the combining property of the hemotoxin upon the mechanism of
      hemolysis and upon the inhibition of the hemolytic reaction was also
      investigated.

PMID- 19869371
TI  - STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES : X.
      IMMUNOLOGICAL DISTINCTIONS BETWEEN THE HEMOTOXIN AND THE "PROTEIN FRACTION" OF
      THE PNEUMOCOCCUS CELL.
AB  - The investigation deals with the immunological differentiation of the hemotoxin
      and the "protein fraction" of Pneumococcus, and with a like differentiation of
      the antihemotoxin and the antiprotein precipitins. The distinction is made upon
      the basis of the following evidence: (1) The antigenic (antibody-invoking and
      antibody-combining) properties of the hemotoxin were destroyed by heat and
      oxidation treatments which did not cause the loss of the antigenic effectiveness
      of the "protein fraction." (2) The removal of the hemotoxin from pneumococcus
      solutions by combination with erythrocytes caused no loss in the capacity of the
      solution to invoke the production of antiprotein precipitins nor in its capacity
      to react with antiprotein immune serum. Titrations of the antihemotoxin content
      of antipneumococcus horse serum (both diagnostic and therapeutic) indicated that
      the heating treatment of the immunization material is the most important factor
      in determining the antihemotoxin content of the immune sera obtained from horses,
      as well as of that from rabbits. A distinction was also made between the
      hemotoxin and the toxic substances ("endotoxin") which cause the acute
      anaphylactoid death of rabbits.

PMID- 19869372
TI  - A COMPARATIVE STUDY OF SMOOTH AND ROUGH PNEUMOCOCCUS COLONIES.
AB  - The characteristic appearances exhibited by the surface colonies of both S and R
      pneumococci in 24 and 48 hour cultures upon rabbit blood agar have been reviewed.
      Emphasis has been laid upon the behavior and structure of the colonies formed by
      R pneumococci, their frequent similarity to the colonies formed by certain
      strains of Streptococcus viridans, and their failure to undergo rapid autolysis
      in the first 48-96 hours, a phenomenon which is highly characteristic of the S
      pneumococcus colonies. With the S pneumococci it has been shown that "pseudo
      rough" colonies may be immediately produced under certain unfavorable cultural
      conditions but such changes in colony morphology as these do not indicate that
      complete dissociation has taken place and that the organisms may be classified as
      true R pneumococci.

PMID- 19869373
TI  - THE OCCURRENCE OF ROUGH PNEUMOCOCCI IN VIVO.
AB  - In a survey of about forty rough methemoglobin-producing colonies in sputum
      cultures from a series of individuals suffering from respiratory infections,
      twelve bile-soluble strains of suspected R pneumococci have been isolated for
      study. Two of these twelve strains have shown both autolysis in saline solution
      and serological reactions characteristic of R pneumococci. The findings offer
      evidence that R pneumococci may occasionally occur in human sputum. Their
      significance as regards the epidemiology of pneumococcus infections and of host
      response is alluded to.

PMID- 19869374
TI  - A STUDY OF THE HERING-BREUER REFLEX.
AB  - 1. Cutting one vagus nerve, while recording the pulmonary ventilation of each
      lung separately, has no unique effect on the ventilation of the denervated lung.
      Both lungs respond to unilateral vagotomy by an equivalent slowing and deepening
      of respiratory movement. 2. When the bronchus to one lung is blocked the first
      effect is a slowing and deepening of the respiratory movements recorded by the
      opposite lung. As oxygen want develops these movements become rapid and shallow.
      3. With a combination of these two conditions, i.e., when the bronchus to one
      lung is blocked and its vagus nerve is severed, the pulmonary ventilation
      recorded by the opposite lung exhibits the same changes as may result from
      unilateral vagotomy alone, unaccompanied by occlusion of the bronchus. 4. From
      these facts it may be concluded that the slowing and deepening of breathing which
      follows unilateral vagotomy does not depend for its occurrence upon the passage
      of air in and out of the bronchus of the lung whose vagus nerve has been
      sectioned. 5. The slowing of respirations after occlusion of the bronchus to one
      lung and section of the corresponding vagus nerve still occurs even though the
      phrenic nerve on the same side has been divided. This indicates that the slowing
      of respirations following unilateral vagotomy does not depend on the movements of
      the diaphragm on the side of vagal section. 6. When the pulmonary artery to one
      lung has been ligated and the vagus nerve on the same side cut, the response of
      the other lung is the same as has been described, namely, its respiratory
      movements become slower and deeper. This is taken as evidence that the results of
      unilateral vagotomy are not dependent upon an intact pulmonary circulation. 7.
      The general conclusions from these experiments are that the slowing and deepening
      of respirations following unilateral vagotomy do not depend upon: (a) Passage of
      air in and out of the trachea. (b) Expansion and collapse of the lung. (c)
      Existence of a normal pulmonary circulation in the vagotomized lung. (d) Normal
      fluctuations in alveolar carbon dioxide tension, (e) Contraction and relaxation
      of the diaphragm on the side of vagotomy. 8. The slowing and deepening of
      respirations, alluded to, may be presumed to indicate that a normal reflex (the
      Hering-Breuer reflex) has been interrupted. Since this interruption occurs in
      spite of all the conditions enumerated under Paragraph 7, we must conclude that
      none of these conditions is essential to the existence of this reflex.

PMID- 19869375
TI  - THE MECHANISM OF THE INFLAMMATORY PROCESS : II. CONCERNING THE ADHESIVE FORCE OF
      ONE PSEUDOPOD OF A FROG LEUCOCYTE AND ITS RELATION TO LEUCOCYTE EMIGRATION.
AB  - Observations on the behavior of a frog leucocyte in vivo have led to the
      conclusion that an adhesive force of at least 10(-5) dynes may be offered by one
      pseudopod. This adhesive force, of one pseudopod, is of the order of magnitude
      sufficient to cause leucocyte arrest previous to emigration through the capillary
      wall.

PMID- 19869376
TI  - THE STRUCTURE OF B. ANTHRACIS AND REVERSAL OF THE GRAM REACTION.
AB  - 1. The addition of small amounts of aqueous gentian violet, acriflavine, or
      acriviolet to suspensions of young cultures of B. anthracis reverses their Gram
      reaction, and diminishes their diameter about 40 per cent. 2. The time required
      for these changes varies with the strain of B. anthracis examined. 3. These
      changes are accompanied by a loss of weight. 4. Ninhydrin-positive substances are
      demonstrable in the filtrate from suspensions of B. anthracis to which dyes have
      been added. 5. Similar changes are produced by these dyes in many, but not in
      all, of the sporogenic aerobes. 6. Non-spore bearers are for the most part
      unaffected in these ways by the dyes, although to this statement there are a
      number of exceptions. 7. The change in size produced by the dyes is demonstrable
      in hanging drop specimens as well as in stained smears, but not with equal
      constancy. 8. Partial decolorizations of B. anthracis are described, which are
      produced by modifications of the Burke technic in which time of exposure to dye
      is shortened and time of exposure to decolorizer lengthened. 9. The explanation
      for these phenomena which accords with all the known facts is that they depend on
      the existence in B. anthracis of a Gram-positive cortex and a Gram-negative
      medulla. Positive proof of the correctness of this explanation must await the
      evidence furnished by cross-sections of bacteria.

PMID- 19869377
TI  - EFFECT OF CERTAIN TISSUE EXTRACTS ON RED BLOOD CELL REGENERATION.

PMID- 19869378
TI  - STUDIES ON THE MODE OF SPREAD OF B. ENTERITIDIS MOUSE TYPHOID INFECTION : I.
      NATIVE EPIDEMICITY.
AB  - Thirteen batches of mice from nine different sources were tested for the presence
      of mouse typhoid bacilli. Individuals from nine of the groups were found to be
      infected with the B. enteritidis type, four with the paratyphoid B, one with
      both, and one with neither type. With two exceptions, smooth type colonies alone
      were found. These results are in conformity with similar observations as reported
      by others and confirm the general belief that smooth colony types of paratyphoid
      enteritidis bacilli prevail throughout the various stages of rodent typhoid
      infection.

PMID- 19869379
TI  - STUDIES ON THE MODE OF SPREAD OF B. ENTERITIDIS MOUSE TYPHOID INFECTION : II.
      EFFECTS OF EXTERNAL CONDITIONS ON THE OCCURRENCE OF SMOOTH, MUCOID, AND ROUGH
      COLONY TYPES.
AB  - The experiments described in this paper are part of a larger number which we have
      been carrying out for the past 2 years. Although they have not entirely fulfilled
      their purpose, which was to explain the so called "mutation," "dissociation,"
      "Umwandlung," "transformation" process, they have served to formulate a helpful
      working hypothesis. Certain difficulties inherent in this kind of study must be
      recognized. One is that colony formation is a property associated with growth on
      solid media and any procedure involving the use of fluid media introduces a
      change which is relatively uncontrolled. Another is that mucoid and rough colony
      forms are not the only variant types encountered; at best, they may be considered
      as being the most frequent. Finally, it is apparent to us that the findings
      reported in this paper with respect to enteritidis organisms do not correspond
      with those of other species of organisms, especially of the respiratory group
      which we have studied (1, b). Possibly, however, they apply generally to the
      typhoid, paratyphoid-enteritidis species. To summarize, it may be stated that the
      transformation process in the mouse typhoid enteritidis group is an easily
      reversible one, controlled in part, at least, by three factors, any of which may
      conceivably operate under natural conditions: (1) temperature, which, influences
      the appearance of mucoid forms; (2) fluidity of culture media, which tends to
      favor rough variants; and (3) bacteriophage, which stimulates the appearance of
      both variants. Since by manipulating these factors the transformation process may
      be incited at will in either direction, it is probably not genetic in nature.

PMID- 19869380
TI  - STUDIES ON THE MODE OF SPREAD OF B. ENTERITIDIS MOUSE TYPHOID INFECTION : III.
      STUDIES OF BACTERIAL CELLS TAKEN FROM SMOOTH, MUCOID, AND ROUGH COLONIES.
AB  - 1. During early stages of multiplication, single cells from smooth-, mucoid-, and
      rough-susceptible and variant colonies show no differences in morphology or
      growth rate. 2. Cells from 18 to 24 hour single cell cultures of these various
      colony types possess similar oxygen absorption and cataphoretic migratory rates.
      In staining property, the cells from mucoid colonies appear larger, and those
      from rough colonies smaller, than the typical cells from smooth-susceptible
      colonies. 3. Cells from bacteriophage-resistant colonies differ from those of
      bacteriophage-susceptible colonies in their ability to multiply luxuriantly in
      the presence of bacteriophage, and in their tendency to flocculate in acid
      solutions at pH 3.8 to 4.1, as well as in their low degree of virulence. 4. Cells
      from smooth bacteriophage-susceptible colonies in contact with bacteriophage
      under conditions where multiplication is restrained may be altered so as to
      resemble the cells from the bacteriophage-resistant colonies. 5. These facts
      furnish evidence that bacteriophage adheres to the surface of the bacterial cell
      and that the various cell changes and colony alterations are of an environmental
      rather than genetic nature.

PMID- 19869381
TI  - STUDIES ON THE MODE OF SPREAD OF B. ENTERITIDIS MOUSE TYPHOID INFECTION : IV. THE
      RELATIVE VIRULENCE OF SMOOTH, MUCOID, AND ROUGH STRAINS.
AB  - 1. Single cell mouse strains of B. enteritidis from smooth-susceptible colonies
      were, under the various conditions tested, of the same high degree of virulence.
      2 year old cultures, strains obtained both in interepidemic and epidemic periods,
      and "reverted" strains from variant colonies showed the same degree of
      pathogenicity. 2. Single cell strains from variant smooth, mucoid,and rough phage
      resistant colonies were definitely less virulent than the usual smooth
      susceptible strains. The loss of virulence in each instance resulted apparently
      from contact with bacteriophage which rendered the individual cells incapable of
      multiplication in the animal tissues. 3. A reduction of virulence was induced
      experimentally when washed cultures of the highly pathogenic smooth-susceptible
      cells were exposed to bacteriophage and thus rendered incapable of multiplication
      in the inoculated animals.

PMID- 19869382
TI  - STUDIES ON BACTERIAL ENZYMES : VI. THE MALTASE OF THE DIPHTHERIA BACILLUS.
AB  - Diphtheria bacilli possess a heat-labile, endocellular maltase, which retains its
      activity in sterile solutions of the intracellular substances which are liberated
      by physical disintegration of the bacterial cells. The proof of the maltase
      activity and the detection of the hexose products constitute experimental
      evidence that the living diphtheria bacillus attacks maltose by way of a
      preliminary hydrolysis.

PMID- 19869383
TI  - STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY : IV. THE
      INHERITANCE OF SUSCEPTIBILITY TO TAR-INDUCED TUMORS IN THE LUNGS OF MICE.
AB  - Evidence has previously been submitted in favor of the theory that susceptibility
      to spontaneous tumors of various types is inherited. The question arose whether
      susceptibility to tumors induced by tar could be shown to be hereditary by
      experimenting with the same strains of mice which had already been shown to
      differ significantly in respect to their spontaneous tumor rates. Two strains of
      mice were selected for observation. One strain, the Bagg albinos, has a low rate
      of mammary gland tumors but a higher rate of spontaneous lung tumors. The other
      strain, No. 1194, agouti, has a higher rate of mammary gland tumors but a lower
      rate of tumors of the lung. A previous test showed no difference in the
      percentages of skin tumors which arose after tar painting. It has already been
      shown that the difference in the lung tumor rates is mathematically significant.
      When the two stocks are treated with tar by applying the irritant, not in the
      same spot, but on different areas successively, the percentage of lung tumors is
      increased in each stock, Text-fig. 11. The rate of the Bagg albinos increased
      from 37.04 to 85 per cent, that of Strain 1194 from 6.73 to 22 per cent. But a
      difference between them is still maintained, and this difference also is
      significant mathematically. When the two strains are crossed and the offspring
      subjected to the tar treatment, the latter give a high percentage of lung tumors
      79 per cent in 28 individuals-about the same as the parental high tumor strain.
      When the F(1) sons are backcrossed to the original See PDF for Structure stocks,
      the cross to the high tumor strain maintains the high tumor rate, 81 per cent in
      37 mice, while in the cross to the low tumor strain the percentage drops to 39
      per cent in 38 mice. This result indicates that susceptibility to tar-induced
      tumors in the lung is hereditary. The number of factors concerned has not yet
      been ascertained. Possibly one or more of them is dominant. In general, the
      conception that susceptibility to pulmonary tumors is hereditary seems to be
      upheld by the fact that the two strains of mice described differ conspicuously in
      respect to spontaneous tumor rates under ordinary laboratory conditions; the
      strains differ also under experimental conditions, as described in this report;
      and when crossed, their offspring by suitable backcrosses, will again show
      significant differences.

PMID- 19869384
TI  - FURTHER STUDIES CONCERNING THE FILTRABLE VIRUS PRESENT IN THE SUBMAXILLARY GLANDS
      OF GUINEA PIGS.
AB  - 1. It has been shown that the guinea pig virus localizes in the submaxillary
      glands of young guinea pigs following subcutaneous, intraperitoneal, or
      intravenous injection of active material, and that the specific lesion is
      demonstrable in the glands in 12 to 15 days. When an active infection of the
      gland has been produced in this way, the guinea pigs are refractory to
      intracerebral inoculation of the virus. 2. No lesion develops in the submaxillary
      glands of young guinea pigs injected subcutaneously with guinea pig virus which
      has been inactivated by heat. Young guinea pigs which have received injections of
      heat-killed virus do not become refractory to intracerebral inoculation of the
      virus. 3. When young guinea pigs from which both submaxillary glands have been
      removed are injected subcutaneously with active virus, the virus localizes in the
      parotid gland, and the animals become refractory to intracerebral inoculation. 4.
      It has been impossible to demonstrate virucidal properties in the sera of adult
      guinea pigs which have become spontaneously infected with the virus, or in the
      sera of young guinea pigs which have been artificially rendered refractory to
      intracerebral inoculation. 5. It has been possible to transmit the virus from
      guinea pig to guinea pig continuously in series through seven animals by direct
      inoculation from submaxillary gland to submaxillary gland. 6. The fact that the
      virus regularly localizes in the submaxillary glands following subcutaneous
      inoculation has been utilized in passing the virus from guinea pig to guinea pig.
      2 weeks after the subcutaneous inoculation of the virus into young guinea pigs,
      the active agent was present in the submaxillary glands. Emulsions of the
      submaxillary glands of these animals were then used for the subcutaneous
      injection of another group of young guinea pigs. In this way the virus was
      transmitted continuously from skin to submaxillary gland through a series of
      seven animals.

PMID- 19869385
TI  - STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS : IV. EFFECTS OF CERTAIN
      PHYSICAL AND MECHANICAL FACTORS ON EXTRACORPOREAL THROMBOSIS WITH AND WITHOUT THE
      USE OF ANTICOAGULANTS.
AB  - The effects of environmental temperature on thrombosis in circulating blood were
      tested in the extracorporeal loop by the method previously described. Cold (7
      degrees to 15 degrees C.) about the collodion tube retards the clotting of
      circulating blood. Obstruction of the arterial cannula occurs after from 15 to 25
      minutes. Heat (40 degrees and 55 degrees C.) tends to hasten clotting;
      obstruction by red clot takes place after from 4 to 6 minutes and from 2 to 4
      minutes, respectively. In the latter case no characteristic thrombus structure
      may be seen. These results were what might be expected. The formation of white
      thrombi occurs even under the influence of cold, and they continue to form and
      grow as long as the circulation continues. When the carotid artery is partially
      occluded and the blood stream slowed, after the injection of the anticoagulant,
      the blood has a tendency to form red thrombi on the foreign surface of the
      vascular loop. The thrombi are deposited chiefly in the arterial half of the
      apparatus, especially at the bottom of the arterial end of the collodion tube,
      just as in the case of Aschoff's sand experiments. In spite of incoagulability of
      heparinized blood, red clots, with interwoven fibrin bands, are found. Also very
      tiny white thrombi may form in other parts of the collodion tube. The effect of
      complete obstruction of the carotid artery and jugular vein on thrombus formation
      was studied after the use of anticoagulant. When the carotid artery is obstructed
      the formation of white thrombi is negligible and sedimentation of erythrocytes
      and deposition of fibrin appear throughout the apparatus; then the blood, at a
      standstill, clots very slowly. When the jugular vein is obstructed, dislodgment
      of platelet thrombi probably results from the pulsating movement, and
      sedimentation of erythrocytes follows, forming mixed thrombi. The dislodged white
      thrombi tend to gather in the bottom of the tubes of the widest caliber,
      especially in the collodion tube.

PMID- 19869386
TI  - STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS : V. INFLUENCE OF CERTAIN
      CHEMICAL SUBSTANCES ON EXTRACORPOREAL THROMBOSIS WITH SPECIAL REFERENCE TO THE
      EFFICACY OF A COMBINATION OF HEPARIN AND MAGNESIUM SULFATE.
AB  - 1. Distilled water dialyzes through the collodion tube and causes hemolysis.
      Clotting of the hemolyzed blood in the collodion tube occurs later. 2. Bile salts
      accelerate the appearance and development of white thrombi in the heparinized
      animal. The masses of white thrombi are very loose, soft, fragile and easily
      broken into clumps of platelets. They are poor in fibrin or the fibrin is
      abnormal, since they have less retractility than those obtained from the use of
      physiologic sodium chloride solution or calcium chloride or serum. Despite the
      increase in number and size of white thrombi, normal clotting does not occur. 3.
      When the collodion tube is surrounded by 1 or 2 per cent d-glucose solution, tiny
      and numerous white thrombi appear as radiating figures. The masses of white
      thrombi are rather loose and fragile. The clotting time of the heparinized blood
      does not appear to be shortened. 4. When a 1 to 2 per cent solution of calcium
      chloride is used as the dialyzing fluid outside the collodion tube, or when it is
      injected into the circulation, the formation of white thrombi is accelerated.
      They grow very rapidly. In spite of the action of heparin, the white thrombi
      formed are not so fragile as when bile salts are placed outside of the collodion
      tube. Fibrin seems to form easily. Obstruction of venous cannula takes place
      speedily and if the clots in the cannula are not removed, the white thrombi in
      the collodion tube remain small and become red by sedimentation of red cells. 5.
      Intravenous use of 10 per cent solution of magnesium sulfate without heparin
      retards the coagulation of circulating blood and permits the blood to flow
      through the extracorporeal loop from three to four times as long as normal. The
      formation of white thrombi, as well as red, is retarded. Magnesium sulfate (1 per
      cent) in physiologic sodium chloride solution placed outside the collodion tube
      markedly retards the formation of white and red thrombi in the heparinized
      animal. Magnesium sulfate (10 per cent), 50 mg. for each kilo of body weight each
      hour, administered intravascularly in the heparinized animal definitely prevents
      the first stages of thrombosis, and consequently prevents clotting. 6. It is
      possible by the combined use of adequate amounts of magnesium sulfate and of
      heparin intravenously to prevent all stages of thrombus formation for from 1 to 3
      hours.

PMID- 19869387
TI  - STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS : VI. CERTAIN TECHNICAL
      MODIFICATIONS IN METHODS OF STUDY.
AB  - As the result of these modifications, many of which in themselves may appear
      trifling, the course of events in the extracorporeal loop is greatly affected.
      White thrombi, it is true, are laid down in from 10 to 20 minutes, but the
      formation of fibrin sufficient to cause obstruction is prevented for 3 hours or
      more. Thus, the observations in normal animals tend to approach those described
      in Paper III, after the use of anticoagulants such as heparin and hirudine. The
      new technic offers certain advantages in the study of the details of the early
      stages of thrombosis.

PMID- 19869388
TI  - THE MECHANISM OF THE INFLAMMATORY PROCESS : I. THE ELECTROPHORESIS OF THE BLOOD
      CELLS OF THE HORSE AND ITS RELATION TO LEUCOCYTE EMIGRATION.
AB  - 1. The velocity of cataphoretic migration of blood cells in plasma and serum is
      proportional to the potential drop applied. 2. The cataphoretic velocity of red
      cells, polymorphonuclear leucocytes, small lymphocytes, and large lymphocytes is
      described for serum and plasma. 3. The relation between the electrokinetic
      potential of white blood cells and the differences of potential probably existing
      in injured tissues are correlated quantitatively. 4. This correlation suggests
      that migration of leucocytes to a point of injury is, in part, dependent upon the
      electromotive forces at play in the tissues.

PMID- 19869389
TI  - LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS : III. INCIDENTAL
      MYELITIS, ABSCESS, AND ORGANIZATION OF EXUDATES.
AB  - 1. In experimental Type I pneumococcal meningitis of dogs central cord
      involvement is common after the 2nd day of the disease. 2. These central cord
      lesions may progress toward extensive suppurative myelitis. 3. Abscesses are
      infrequent; they arise either as direct perivascular extensions of the meningeal
      disease or at the site of infected purpuric lesions. 4. In prolonged untreated
      meningitis of reinfected animals, nothing resembling the disappearance of exudate
      following crisis in pneumonia occurs. The tendency is toward organization. 5.
      Late lesions are characterized by the marked development of a perivascular
      clasmatocytic apparatus, similar to, but more extensive than that hitherto
      reported in experimental herpetic encephalitis.

PMID- 19869390
TI  - CHANGES IN THE PERCENTAGE OF CALCIUM AND PHOSPHORUS OF THE BLOOD FOLLOWING
      SECTION OF THE SYMPATHETIC AND VAGUS NERVES.
AB  - When a splanchnic nerve or the celiac plexus was severed a definite fall in serum
      calcium resulted, the level falling to 6 mg. per cent and remaining low for 1 or
      2 weeks. Tetany, however, did not develop. The inorganic phosphate was slightly
      altered. On the other hand, when the vagi nerves were severed, the serum calcium
      rose. The equilibrium of both calcium and phosphorus was rendered less stable by
      the division of the sympathetic or the parasympathetic nerves.

PMID- 19869391
TI  - ALTERATIONS IN THE CALCIUM LEVEL OF THE BLOOD FOLLOWING SECTION OF THE SPINAL
      CORD.
AB  - A marked rise and disturbance in equilibrium of the calcium in the blood was
      brought about by section of the spinal cord in the upper dorsal segment. This
      reaction, however, was not constant.

PMID- 19869392
TI  - RECENT STUDIES ON METHODS OF ISOLATING A BACTERIOPHAGE FOR BACILLUS DIPHTHERIAE.
AB  - Of the attempts to isolate an antidiphtheria phage (1) from stools collected
      daily during the course of a case of the disease, (2) from a 33 day old broth
      culture of B. diphtheriae, (3) from intestinal contents and peritoneal washings
      of guinea pigs inoculated with three different toxic strains of B. diphtheriae,
      none yielded an antidiphtheria phage. However of eleven specimens of feces
      collected from eleven antitoxin horses one was found to contain a bacteriophage
      active against B. diphtheriae. This phage was not observed in the first
      generation and did not show up until transferred the second time. Had the results
      of the first transfer been regarded as final in all certainty the existence of a
      phage would not have been recognized. Two additional specimens of feces from the
      positive horse (No. 156) were later tested to determine whether this
      bacteriophage was continually present in the intestinal tract of this animal.
      Both of these feces filtrates failed to yield a phage. Later a sample of freshly
      collected blood serum from the same horse was tested and found not to contain a
      phage. The antidiphtheria phage was tested against eighteen non-diphtheria
      strains of microorganisms to determine whether it would show lytic activity for
      related or unrelated bacteria. There was no evidence of lysis in any of these
      types. The specificity of this phage was also tested on nine strains of B.
      diphtheriae and found to be active on three heterologous strains (Strain M 1314,
      Strain F and Strain G). These incidentally were all recently isolated. It failed
      to lyse the remaining six strains of which five were recently isolated. B.
      diphtheriae Strain M 1314 was used in combination with nine heterologous
      bacteriophages isolated from various sources, to determine if any of these phages
      would by chance lyse this culture. The results were all negative. To date this
      phage fails to show complete lysis although the twenty-second generation has a
      titer of 1 x 10(-9). Additional proposed experiments involving this phage are
      being planned and will be undertaken in the near future.

PMID- 19869393
TI  - THE INFLUENCE OF HEATING THE IMMUNIZATION MATERIAL UPON THE ANTIBODY-INVOKING
      EFFECTIVENESS OF THE TYPE-SPECIFIC AND SPECIES-SPECIFIC ANTIGENS OF TYPE II
      PNEUMOCOCCUS CELLS.
AB  - This paper presents an experimental comparison of the effect of heating of the
      immunization material upon the antibody-invoking effectiveness of the type
      specific (SP) and species-specific (P) antigens of Type II pneumococci. Heating
      of the pneumococcus suspension (vaccine) invariably decreased the production of
      species-specific antibodies (anti-P) without a comparable effect upon the
      production of type-specific antibodies (anti-S). For diagnostic typing purposes,
      the ideal antipneumococcus serum should contain the maximum content of type
      specific, and the minimum of species-specific antibody. Our results with forty
      one rabbits indicate that the ideal serum from the type-specific standpoint would
      be obtained by immunization with the heated cells of virulent pneumococci over a
      comparatively short immunization period; and that the only thing gained by
      continued immunization or by the use of unheated bacteria at any stage of the
      immunization, is an increase in the species-specific antibody which is
      undesireable in sera to be used for diagnostic purposes.

PMID- 19869394
TI  - STUDIES ON STREPTOCOCCUS BACTERIOPHAGE : II. THE INFLUENCE OF LYTIC PRINCIPLES
      UPON THE AGGLUTINATION OF HEMOLYTIC STREPTOCOCCI.
AB  - A series of experiments was carried out on various strains of streptococci in
      order to ascertain the changes which bacteriophage produces in the phenomena of
      agglutination of these organisms. The results can be placed in the following
      categories. 1. Loss of specific agglutinability was observed with partial and
      with what appeared as complete loss of specific agglutinin absorption and
      agglutinogenic properties. 2. Partial modification of the antigen, bringing about
      inagglutinability of the strains with complete preservation of agglutinogenic and
      agglutinin-absorption properties. Coincidentally, additional components appeared.
      Some of these were related to the specific antigens of the organisms from which
      they were derived, while others were not. In two instances these components were
      of "group" character. 3. "Complete" modification observed with two strains
      consisting of complete transformation of the normal culture agglutinogens into
      antigens of an entirely different specificity. It appears from these studies that
      the bacteriophage phenomenon may play an intricate ro1e in serological grouping
      of various strains of pathogenic streptococci.

PMID- 19869395
TI  - ETIOLOGY OF OROYA FEVER : IX. BACTERIUM PERUVIANUM, N. SP., A SECONDARY INVADER
      OF THE LESIONS OF VERRUGA PERUANA.
AB  - A minute, pleomorphic, motile, Gram-negative bacterium has been isolated from two
      specimens of nodular tissue from human verruga. In films and sections of the
      original tissues the organism in question is difficult to distinguish from
      Bartonella bacilliformis, with which it was associated, and even in pure culture
      it has a number of properties in common with that parasite. No sugars are
      fermented by it, it is an obligate aerobe, the optimum temperature for its growth
      is 25 degrees C., and it has two to four spiral flagella attached to one end of
      the body. It is, however, readily cultivated on any ordinary culture medium.
      Broth cultures contain much mucin, but no hydrogen sulfide is formed. Coagulated
      serum is liquefied by its growth, and the red corpuscles in a blood agar plate
      are hemolyzed. Rabbits, guinea pigs, rats, and mice develop acute, fatal
      septicemia as a result of intravenous or intratesticular inoculation of young
      cultures. The liver is characteristically affected and shows a general
      parenchymatous degeneration and necrosis; the entire gastrointestinal tract is
      intensely congested, and numerous hemorrhagic areas are present; the spleen, dark
      and soft, is rarely much enlarged; the kidneys are swollen and congested; the
      adrenals are much swollen and intensely red; the lungs are sometimes congested
      but otherwise normal. In the case of intratesticular inoculation the scrotum and
      testicle both undergo rapid gangrene. In monkeys no septicemia has been observed,
      but a violent local reaction-swelling, congestion, sometimes necrosis-follows
      intradermal inoculation. Since no microorganism corresponding in character with
      this one has previously been described, it is regarded as a new species, and
      because of its presence in material obtained from Peru it has been given the name
      Bacterium peruvianum. The significance of the association of B. peruvianum with
      Bartonella bacilliformis deserves further investigation; it is not impossible
      that the two organisms are introduced into the human body by the same blood
      sucking insect.

PMID- 19869396
TI  - ON PRECIPITABLE SUBSTANCES DERIVED FROM BACILLUS TYPHOSUS AND BACILLUS
      PARATYPHOSUS B.
AB  - Attempts to confirm certain statements that ether-soluble specific substances can
      be obtained from B. typhosus have lead to negative results. Two serologically
      active protein substances and another that was non-protein have been separated
      from B. typhosus. The first two are not resistant to tryptic digestion or to
      treatment with alkaline hypochlorite solution whereas the third resists both. One
      of the proteins could be extracted with 75 per cent alcohol. Specific
      precipitable substances reacting like the non-protein substance of B. typhosus
      and containing large amounts of carbohydrates have been prepared from B.
      paratyphosus B, B. enteritidis, and Proteus HX19 and OX19. Observations on the
      serological behaviour of these preparations are described.

PMID- 19869397
TI  - CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS : V. HERPES
      VIRUS ENCEPHALITIS IN THE GUINEA PIG.
AB  - The guinea pig is subject to cerebral and corneal inoculation of the herpes
      virus. The effects of the inoculations vary with the strength or degree of
      virulence of the virus. Weak strains of the virus are implanted on the cerebrum
      with difficulty and strong strains with ease. Weak strains are quickly suppressed
      by the brain and strong strains may be passed indefinitely from brain to brain of
      the guinea pig. Strains of intermediate potency can be passed for a limited
      number of times only. Weak strains induce keratoconjunctivitis without brain
      involvement, while strong strains invade the brain from the eye and produce fatal
      encephalitis. In the latter case, the brain contains active virus inoculable upon
      the cornea and into the brain of rabbits and guinea pigs. Strains of intermediate
      potency produce keratoconjunctivitis accompanied by mild symptoms of
      encephalitis, from which recovery results. The guinea pig serves even more
      definitely than the rabbit to distinguish grades of virus according to strength
      or virulence. There is no difference of kind but only of degree of response to
      inoculation of herpes virus in the rabbit and the guinea pig. The etiology of
      epidemic encephalitis has not, therefore, been brought appreciably nearer
      solution by experiments with herpes virus carried out in guinea pigs.

PMID- 19869398
TI  - ULTRA-VIOLET LIGHT AND VACCINE VIRUS : I. THE REACTION OF IRRADIATED SKIN TO
      VACCINE VIRUS.
AB  - Rabbit skin treated for a few minutes with ultra-violet light and then inoculated
      at once with vaccine virus is less susceptible to the action of the virus than is
      untreated skin. If 24, 48, or 72 hours elapse between the time of irradiation and
      inoculation, the treated skin appears to be more susceptible than is untreated
      skin. Skin repeatedly exposed to ultra-violet light is less susceptible to the
      action of vaccine virus than is non-irradiated skin.

PMID- 19869399
TI  - ULTRA-VIOLET LIGHT AND VACCINE VIRUS : II. THE EFFECT OF MONOCHROMATIC ULTRA
      VIOLET LIGHT UPON VACCINE VIRUS.
AB  - Under the experimental conditions described in the present paper, it was found
      that the amount of energy required to kill staphylococci at single wave-lengths
      in the active ultra-violet region was approximately the same as that necessary to
      inactivate vaccine virus.

PMID- 19869400
TI  - COMPENSATORY HYPERTROPHY OF THE LUNG AFTER UNILATERAL PNEUMECTOMY.
AB  - In the albino rat the removal of the left lung, which constitutes about one-third
      of the total lung tissue, is followed by an average increase of more than 40 per
      cent in the mass of the remaining lung, as estimated from the nitrogen content of
      the almost blood-free tissue.

PMID- 19869401
TI  - THE PRECIPITIN REACTION OF ANTIPNEUMOCOCCUS SERA : I. THE PRECIPITIN INDEX.
AB  - The mechanism of the precipitin reaction between antipneumococcus sera and the
      type-specific soluble carbohydrate is investigated. The sensitivity of the
      reaction is found to be generally constant when expressed by the product of the
      concentrations of the two reacting substances. Precipitin index (P.I.) is defined
      as one-millionth of the reciprocal value of this product. See PDF for Structure
      Zonal phenomena and their bearing on the absolute concentration and the
      equivalent weight of the antibody are discussed. The greater tendency towards
      exhibition of a post-zone in Type III is connected with the lower acid equivalent
      of the homologous specific carbohydrate. The influence of the addition of normal
      serum and the influence of slight changes in pH are studied. The addition of
      normal serum as well as the increase in pH promote the pro-zone, whereas decrease
      in pH promotes the post-zone. The sensitivity of the reaction is accordingly
      influenced by the pH in different ways depending on the range of concentration.
      The precipitin index allows the recognition and elimination of zonal
      irregularities. Thus it offers a method for the standardization of pneumonia
      antibody.

PMID- 19869402
TI  - THE PRECIPITIN REACTION OF ANTIPNEUMOCOCCUS SERA : II. THE RATIO OF PRECIPITIN TO
      PROTECTIVE ANTIBODY.
AB  - The precipitin indices for a number of monovalent and polyvalent antipneumococcus
      sera were determined under known conditions, and found to vary as did the number
      of protective units. The ratio precipitin index/protective units in monovalent
      sera was found to lie between 2.8 and 4.8 for Type I and to be about ten times
      greater for Type III. Lower values were found in polyvalent horses and when
      mixing heterologous monovalent sera with each other. The influence of the
      duration of treatment upon the quotient was studied. Several refined and
      concentrated preparations showed a relative increase in precipitin activity.

PMID- 19869403
TI  - CONTRIBUTIONS TO THE PATHOLOGY OF EXPERIMENTAL VIRUS ENCEPHALITIS : IV. RECURRING
      STRAINS OF HERPES VIRUS.
AB  - In this paper, three strains of the herpes virus have been dealt with. The H.F.
      II strain was obtained from the subject H.F. 4 years after the H.F. I strain was
      secured. H.F. is a victim of recurrent herpes. If the subject is also a chronic
      carrier of the herpes virus, then it is not one, but two or more strains which
      are persistently carried. The H.F. II strain is of mitigated pathogenic action
      for the rabbit, as compared with the H.F. I strain; it is to be classed as
      dermatotropic rather than neurotropic. And yet, in the subject there was no
      indication that the attack of herpes provoked was different from the other
      attacks associated with the H.F. I virus. The other two herpes strains derive
      their interest from the fact that they came also from persons who suffer from
      repeated attacks of labial herpes. One strain proved highly neurotropic,
      resembling in this respect the H.F. I strain; the other was hardly neurotropic at
      all, but was none the less definitely dermatotropic. It may be possible at a
      later date to secure other samples of virus from these individuals for
      comparison. The dermatotropic F. strain penetrates to the central nervous system
      far more readily and certainly from the skin than from corneal surfaces. The
      recovered inoculated rabbits showed only relative protection to reinoculation of
      the herpes virus. A notable difference appeared in the degree of protection
      acquired, on the one hand by the cornea and on the other by the brain. While the
      one was partial, the other was complete. The complete resistance of the brain was
      shown (a) by the complete failure of the intracerebral inoculation, and (b) by
      the absence of circling movements following corneal inoculation.

PMID- 19869404
TI  - THE ANTIGENIC COMPLEX OF STREPTOCOCCUS HAEMOLYTICUS : I. DEMONSTRATION OF A TYPE
      SPECIFIC SUBSTANCE IN EXTRACTS OF STREPTOCOCCUS HAEMOLYTICUS.
AB  - 1. Hydrochloric acid extracts of Streptococcus haemolyticus contain type
      specific, as well as non-type-specific, substances. The precipitates formed by
      these crude extracts with homologous antibacterial serum are flocculent, while
      those obtained with heterologous serum are usually disc-like. 2. The type
      specific substance may be detected by the use of anti-bacterial sera absorbed
      with heterologous strains of hemolytic streptococci. Such absorbed sera are type
      specific: they are precipitated only by extracts of strains of the homologous
      type. 3. Any heterologous strain of hemolytic streptococcus absorbs the
      antibodies for all other heterologous strains, but homologous strains absorb type
      specific antibodies as well. Numerous repeated absorptions with heterologous
      hemolytic streptococci tend to lower the titer of the type-specific antibody. A
      possible explanation of this fact is suggested. 4. Three strains did not yield a
      type-specific substance; and it seems probable that they had lost this function
      because of long continued cultivation in artificial media. 5. Classification
      based on the precipitin test with absorbed serum agrees with that previously
      determined by agglutination and protection tests. The method is, therefore,
      applicable to the problem of classification of the hemolytic streptococci.

PMID- 19869405
TI  - THE INFLUENCE OF THE ADRENAL GLANDS ON RESISTANCE : III. SUSCEPTIBILITY TO
      HISTAMINE AS A TEST OF ADRENAL DEFICIENCY.
AB  - 1. The resistance of rats to histamine is greatly diminished after adrenalectomy.
      2. This susceptibility to histamine is proposed as a functional test for
      deficient adrenal cortex function.

PMID- 19869406
TI  - STUDIES IN THE COMMON COLD : II. A STUDY OF CERTAIN GRAM-NEGATIVE FILTER-PASSING
      ANAEROBES OF THE UPPER RESPIRATORY TRACT.
AB  - 1. A study of the Gram-negative, filter-passing, anaerobic organisms, described
      by Olitsky and Gates, and Gates and McCartney, has been undertaken with a view to
      determining their general character and their possible role in the causation of
      the common cold. 2. These organisms seem to constitute part of the normal flora
      of the upper respiratory tract and would seem to bear no etiological relationship
      to the common cold.

PMID- 19869407
TI  - STUDIES ON A PARATYPHOID INFECTION IN GUINEA PIGS : IV. THE COURSE OF A SECOND
      TYPE OF SALMONELLA INFECTION NATURALLY APPEARING IN THE ENDEMIC STAGE.
AB  - The course is considered of a second type of Salmonella infection naturally
      appearing in a guinea pig population during the endemic stage of an earlier
      outbreak. After a quiescent period of 5 months the percentage mortality increased
      abruptly; fluctuated, with a second rise during the 9th month; and then declined.
      With the exception of a high rate during the 2nd month the percentage mortality
      from the initial infection tended to remain on a low level. The spread of
      infection in the cages of the breeding stock is recorded from the time of the
      first fatal case. There was a slow but general dissemination of the second
      organism through the group. Fatal cases were confirmed solely to the sows. It is
      suggested that a lowered individual resistance occuring during pregnancy might be
      associated with the regular cage spread and with the apparent difference in
      susceptibility of the sexes. Natural host resistance, virulence of the organisms
      and acquired host resistance are discussed from the standpoint of their bearing
      on the unequal distribution of deaths from the two infections.

PMID- 19869408
TI  - ETIOLOGY OF OROYA FEVER : X. COMPARATIVE STUDIES OF DIFFERENT STRAINS OF
      BARTONELLA BACILLIFORMIS, WITH SPECIAL REFERENCE TO THE RELATIONSHIP BETWEEN THE
      CLINICAL TYPES OF CARRION'S DISEASE AND THE VIRULENCE OF THE INFECTING ORGANISM.
AB  - Through the cooperation of Dr. Sebastian Lorente, Director of the National
      Department of Public Health of Peru, nine strains of Bartonella bacilliformis
      have been isolated, by means of the semisolid leptospira medium, from nine of
      twelve specimens of blood withdrawn from cases of verruga and forwarded from Peru
      under conditions of refrigeration. The cultural titer of the blood specimens
      immediately after their arrival (2 weeks after withdrawal) varied from 1:10 to
      1:100,000. Blood from the severe anemic type of the disease, in which there was
      no eruption, had the highest titer. Blood agar slants yielded irregular results,
      but some strains grew well on these media. Morphologically the strains differed
      very little in fresh preparations examined by dark-ground illumination. In
      stained preparations some strains appeared coarser, others finer than the
      average. Special staining indicated that the flagella were characteristically
      unipolar and varied in number from one to four, some strains showing distinctly
      more wavy and heavier flagella than others. Young cultures grown on the surface
      of horse blood agar for 3 to 6 days show individuals with fairly sharp contours,
      short rods, often varying in thickness toward one or both ends, being
      intermingled with smaller oval or coccoid elements. Some strains show a
      predominance of bacillary, some of coccobacillary forms. It is not known whether
      these features are inherent or are due to conditions of growth, which, though
      identical, may react differently upon different strains. Definiteness in outline
      disappears with the age of the culture. More striking variations are found in the
      virulence of the different strains for the monkey (Macacus rhesus). Three of the
      nine strains isolated proved to be non-pathogenic for the monkeys. All three of
      these were derived from cases of benign verruga. The remaining six strains all
      gave rise to local lesions when intradermally inoculated and were recovered in
      culture from the blood of the animals. So far, severe anemia has not developed in
      any of the monkeys. It is significant that most of the severe cases yielded
      virulent strains, while some of the strains from benign verruga were non
      pathogenic. It appears highly probable that the severe form of Carrion's disease
      is, in general, caused by a virulent strain, while the benign forms are due to a
      strain of low virulence. On the other hand, a virulent strain may cause benign
      verruga in unusually resistant persons and a weak strain may give rise to severe
      blood infection in unduly susceptible individuals. The form of Carrion's disease
      is probably determined primarily by the inherent virulence of the strain of
      Bartonella bacilliformis and is modified secondarily by individual predisposition
      in a given case. An interesting phenomenon brought out by the present
      investigation was the failure of the nine human blood specimens to induce local
      verruga in the same monkeys in which the corresponding cultures, inoculated
      simultaneously at separate sites, gave rise to typical lesions. Yet the original
      blood samples were shown by cultivation to have contained live bartonellas at the
      time they were inoculated, and blood culture revealed the presence of the
      microorganisms in the blood of monkeys which showed no other signs of infection
      after inoculation with the human blood. Whether this striking difference is
      merely a quantitative one or is due to some factor still unknown-such as, for
      example, a biological phase of the microorganism-has not been determined. The
      uniformly negative results of transmission experiments with blood by previous
      investigators is explained by an actual inability of the blood to induce skin
      lesions and the lack, until now, of a reliable method of detecting Bartonella
      bacilliformis in the monkeys' blood. The strains isolated showed similar
      serologic properties, as tested by complement fixation.

PMID- 19869409
TI  - ETIOLOGY OF OROYA FEVER : XI. COMPARISON OF BARTONELLA BACILLIFORMIS AND
      BARTONELLA MURIS. CULTIVATION OF BACTERIUM MURIUM, N. SP.
AB  - Bartonella muris appeared in the blood of all white rats, wild rats, Chinese
      hamster, and mice, from which the spleen was removed, but did not appear in that
      of splenectomized monkeys, rabbits, or guinea pigs. It has not been possible to
      transmit B. muris to normal rats, monkeys, rabbits, or guinea pigs, by
      intraperitoneal, intradermal, or intravenous injection of blood containing B.
      muris from splenectomized rats. In two instances an acute orchitis was induced in
      normal rats by injection directly into the testicle of blood or saline
      suspensions of the liver of splenectomized rats. The intracorpuscular elements
      occasionally identified as B. muris or as having appeared as a result of the
      inoculation. The acute orchitis of rats was transferable to normal rats in
      series. From the testicular tissue, as well as directly from the blood of a
      splenectomized rat, there was isolated in pure culture a microorganism which
      induced in the testicles of normal rats an acute orchitis such as resulted from
      inoculation of the blood or liver suspensions of splenectomized rats. While a few
      inclusions were found in the erythrocytes of some of the animals, their number
      was so small and their occurence so infrequent that they could not be definitely
      identified as B. muris. In morphological features the cultural forms of the
      microorganism isolated resemble B. muris. The organism found in the testicular
      tissues, however, is considerably coarser than B. muris and takes a deeper stain.
      Immunological study failed to settle the question of the relation between B.
      muris and the cultivated organism, which is provisionally called Bacterium
      murium. Bartonella muris, Bartonella bacilliformis, and Grahamella talpae have
      characteristic individual morphological features.

PMID- 19869410
TI  - THE EFFECT ON SUBSEQUENT AGGLUTINATION OF THE EXPOSURE OF BACTERIA TO HEATED
      ANTISERUM.
AB  - It is shown that when dilute rabbit serum rich in agglutinin for the hog cholera
      bacillus is heated at 75 degrees C. for 20 minutes and the bacilli incubated with
      the heated serum, agglutination fails to result on the addition of unheated
      immune serum. When the immune serum is first heated to 80 degrees C., it no
      longer greatly inhibits secondary agglutination when the organisms are exposed to
      fresh agglutinin. The abortion bacillus agglutinin acts in a similar manner
      except that the immune serum must be heated above 80 degrees C. for 20 minutes to
      prevent the second agglutination. The reactions are specific since control
      experiments with normal rabbit serum heated at various temperatures failed to
      influence further agglutination. It has also been shown by precipitation tests
      that there is definite fixation of serum proteins and bacterial cells with the
      heated sera which would prevent subsequent agglutination. Furthermore, heated
      antiserum which would prevent the secondary agglutination still possessed the
      property of deviating complement in a hemolytic series.

PMID- 19869411
TI  - A COMPARISON OF THE SPIROCHETE OF YELLOW FEVER (LEPTOSPIRA ICTEROIDES NOGUCHI)
      WITH THE LEPTOSPIRA OF WEIL'S DISEASE.
AB  - The most noteworthy point observed in our studies is the extraordinary duration
      of life and the relatively meagre requirements for sustenance of Leptospira
      icteroides. It is conceivable that under natural conditions opportunities might
      arise for the prolonged existence of Leptospira icteroides, so that possibly
      after a lapse of years, the disease might reappear without introduction from
      outside. At any rate, the great viability of Leptospira icteroides must be
      considered in this connection. A decrease in the virulence of the leptospira does
      not rule out the possibility of a renewed outburst of yellow fever, since
      Uhlenhuth and Zuelzer have shown that it is possible to set up Weil's disease in
      guinea pigs by means of apparently saprophytic spirochetes obtained from drinking
      water, when the virulence of these organisms has been artificially heightened.

PMID- 19869412
TI  - THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : V. PHENOMENA OF PASSIVE
      IMMUNITY IN BLOCKED AND SPLENECTOMIZED MICE.
AB  - 1. Blockade of the reticulo-endothelial system by means of one intravenous
      injection of India ink as well as splenectomy did not alter the course of either
      Pneumococcus Type I infection or tetanus intoxication in mice. 2. The protective
      action of Antipneumococcus Type I serum against the corresponding infection, as
      determined by the injection of in vitro prepared mixtures of serum and culture,
      was definitely lower in mice which had received one blocking injection of India
      ink shortly before the test. 3. Titration of tetanus toxin and antitoxin in
      blocked and splenectomized mice gave results identical with those obtained in
      normal mice, if in vitro prepared and incubated toxin-antitoxin mixtures were
      injected. The degree of protection, however, conferred by a preceding dose of
      antitoxin against subsequent intoxication, was markedly lower in blocked mice
      than in normal control animals, this difference becoming more pronounced with the
      increase of the time interval.

PMID- 19869413
TI  - THE EXTENT OF THE CAPILLARY BED OF THE HEART.
AB  - By means of injections made into the coronary arteries of beating hearts it has
      been possible to determine the number of capillaries in the normal heart muscle.
      This study has shown a very rich blood supply with an average of approximately
      one capillary for each muscle fibre in the ventricular walls and papillary
      muscles, and a less abundant supply in the auricular muscle and Purkinje system.
      The number of capillaries per sq. mm. of ventricular wall or papillary muscle is
      about twice that found by Krogh in skeletal muscle. Capillaries were not found
      constantly in the valves of hearts in which there was apparently a complete
      injection of the capillary bed. The method described for injecting the
      capillaries of the heart also provides a means of studying the blood supply to
      the muscle, valves and aortic wall in pathological hearts.

PMID- 19869414
TI  - THE ROLE OF THE THEBESIAN VESSELS IN THE CIRCULATION OF THE HEART.
AB  - In summary, evidence has been presented to show a direct connection other than
      through the capillaries between the coronary arteries and the chambers of the
      heart. This connection was shown by perfusion, injections and serial sections to
      be through the Thebesian veins. Communications between the larger coronary veins
      and the Thebesian veins were also demonstrated by the same methods. Serial
      sections through Thebesian veins have shown capillaries draining directly into
      them. Under certain conditions it has been shown that as much as 90 per cent of
      the arterial flow may escape via the Thebesian vessels. Lastly, in the event of
      gradual closure of the orifices of the coronary arteries, the Thebesian vessels
      can supply the heart muscle with sufficient blood to enable it to maintain an
      efficient circulation.

PMID- 19869415
TI  - A STUDY OF THE MECHANISM OF RECOVERY FROM EXPERIMENTAL PNEUMOCOCCUS INFECTION.
AB  - A study was made of the blood of cats and rabbits during experimental
      pneumococcus infection with a view to ascertaining the relationship of acquired
      immune properties to the mechanism of recovery. Observations were directed
      chiefly towards the detection of pneumococcidal promoting substances, but the
      other manifestations of anti-pneumococcus reaction were studied as well. It was
      found constantly that the serum of animals recovering from infection possessed
      the power to promote the destruction of highly virulent pneumococci in rabbit
      serum-leucocyte mixtures which mixtures of themselves have no growth inhibitory
      action. Furthermore, the presence of this serum immunity was associated with a
      marked increase in acquired resistance to the pneumococcus. In cats which were
      studied in the most detail the pneumococcidal promoting power of the serum as
      well as the opsonic, agglutinative, and mouse protective activities became
      demonstrable at the time of recovery and their appearance in the serum always
      marked the termination of blood invasion. These immune reactions were found to be
      type-specific. The animals which succumbed failed to develop detectable serum
      immune properties and showed persistent blood invasion. The degree of
      leucocytosis did not appear to bear any constant relation to the outcome of the
      disease. The significance of these findings is discussed.

PMID- 19869416
TI  - SOME FACTORS DETERMINING THE LOCALIZATION OF A CHICKEN TUMOR AGENT.
AB  - A localization out of the blood stream of the agent causing a chicken tumor, with
      the subsequent development of the growth can be brought about in the breast
      muscle, by inducing in this tissue a reaction by such substances as Scharlach R,
      tar, embryonic tissue and kieselguhr. Localization in the reaction tissue
      elicited by kieselguhr takes place relatively infrequently. The earlier stages of
      the reaction induced by these substances localize the tumor agent more regularly
      than the later stages of the reaction.

PMID- 19869417
TI  - THE EFFECT OF DIGESTS OF PURE PROTEINS ON CELL PROLIFERATION.
AB  - 1. The pepsin hydrolytic products of the pure proteins, crystalline egg albumin,
      crystalline edestin, and purified fibrin, are utilized by fibroblasts for their
      proliferation. It appears, therefore, that the growth of fibroblasts in fibrin
      digests and in the proteose of Witte's peptone is due to the split products of
      the protein itself and not to accompanying cellular constituents or other
      impurities. Preliminary denaturation of the protein, as carried out in these
      experiments, does not alter the nutritive properties of the digest. 2. The
      digests of the pure proteins employed are deficient in certain substances and do
      not meet the entire nutritive requirement of the cells for an unlimited period of
      time. Some supplementary nutritive substances are present in fresh embryonic
      heart tissue. This circumstance explains the growth of fibroblasts from fresh
      embryonic heart in digests which do not promote the growth of a pure strain of
      fibroblasts. 3. Glycocoll and nucleic acid have been found to supplement the
      nutritive action of pure protein digests for sarcomatous fibroblasts, and to
      increase greatly the length of life of the tissues. 4. Vegetable proteins, as
      well as animal proteins, yield proteolytic products which promote the
      multiplication of fibroblasts.

PMID- 19869418
TI  - EFFECT OF LIVER AND PITUITARY DIGESTS ON THE PROLIFERATION OF SARCOMATOUS
      FIBROBLASTS OF THE RAT.
AB  - 1. A media containing all the essential constituents for the cultivation in vitro
      of sarcomatous fibroblasts of the rat has been prepared by digesting calf liver
      and also the anterior lobe of the pituitary body with pepsin. 2. The nutritive
      action of the pituitary digests is not altered by thorough extraction with ether.
      3. After a pure strain of sarcomatous fibroblasts had been cultivated for 3
      months in a liver digest, its proliferative activity was as great as at the
      beginning of the experiment. The same was true of the colonies cultivated for 1
      month in a digest of pituitary gland. The increase in the volume of the colonies
      which takes place in the digests is about as great as that produced by chick
      embryo juice. 4. Normal chicken fibroblasts also proliferate in both digests, but
      they undergo fatty degeneration after a more or less prolonged period of
      cultivation.

PMID- 19869419
TI  - ON THE ROLE OF CARBOHYDRATE HAPTENS IN BACTERIAL ANAPHYLAXIS.
AB  - 1. In passively sensitized animals bacterial anaphylaxis has been produced, in
      vivo and in vitro, with haptens from B. lactis aerogenes, the pneumobacillus, and
      a yeast. 2. The smallest amount of hapten causing fatal anaphylaxis is less than
      the minimal amount of protein which will cause death in properly sensitized
      animals. 3. The haptens used were largely carbohydrates, and gave none of the
      protein reactions, but since they did contain a small amount of nitrogen we
      cannot yet assert positively that carbohydrate alone will produce shock. 4. Since
      haptens will not sensitize animals we must conclude that the anaphylactogenic and
      shock-producing parts of the antigen are not identical. 5. These experiments
      provide further evidence of the close relationship of precipitins to anaphylaxis.

PMID- 19869420
TI  - STUDIES ON THE INACTIVATION OF VACCINE VIRUS AND THE ACTION OF CERTAIN SUBSTANCES
      UPON THE INFECTING POWER OF THE INACTIVATED VIRUS.
AB  - Vaccine virus, obtained from testicular inoculation shows a high susceptibility
      to chloroform as compared with ether, toluene, 95 per cent alcohol and acetone.
      Vaccine virus, after treatment with an amount of chloroform sufficient to render
      it incapable or only barely capable of originating an eruption in the rabbit's
      skin, produces a characteristic eruption when injected with the supernatant fluid
      of embryonic tissue or sarcoma tissue "cultures" or kieselguhr, substances all of
      which are markedly irritative to the rabbit's skin. Reactivation of the
      chloroformed vaccine virus is not possible when chloroform has been added to it
      in such quantity that the injection of large amounts of the treated virus fails
      to cause an eruption. Whenever reactivation has been accomplished it has been
      possible to get a vaccine eruption of greater or less intensity by the injection
      of large amounts of the chloroformed vaccine alone. Embryo and chicken sarcoma
      "culture" fluids when injected intradermally make the skin susceptible to the
      localization of the virus introduced intravenously. The bearing of these
      experiment on the interpretation of Gye' theory of cancer causation is discussed.

PMID- 19869421
TI  - A STUDY OF THE MECHANISM OF NUCLEINATE-INDUCED LEUCOPENIC AND LEUCOCYTIC STATES,
      WITH SPECIAL REFERENCE TO THE RELATIVE ROLES OF LIVER, SPLEEN, AND BONE MARROW.
AB  - The leucopenia induced by sodium nucleinate has been followed by repeated counts
      made simultaneously from the blood of a peripheral vein and from the internal
      organs, combined with a study of histological sections of the same organs taken
      with the counts. Measurements with the oncometer of changes in volume of the
      spleen have been correlated with the leucopenia and the leucocytosis following
      sodium nucleinate. It has thus been determined that the leucopenia is not the
      result of a vasomotor phenomenon, or of a change in blood volume, nor is it
      secondary to a retention of the white cells in the capillaries of lung or liver;
      it is due to the accumulation of neutrophilic leucocytes in the parenchyma of the
      spleen. That the spleen is solely responsible for the temporary depression of
      white cells in the general circulation under these conditions has been shown by
      splenectomy. In splenectomized rabbits no leucopenia developed, but instead a
      leucocytosis due to a direct action on the bone marrow. A profound change occurs
      in the distribution of the cells in the circulation at the moment of death. The
      liver, within a minute of the cessation of the circulation, shows a three- to
      fourfold increase in the number of white cells per c.mm., the differential count
      remaining unchanged. Thus estimations of the physiological distribution and
      redistribution of cells in the living state may be made only with the circulation
      unimpaired. The injection into normal rabbits of adenine and guanine nucleotides,
      split products of nucleic acid, gave immediate leucocytosis of bone marrow origin
      similar to that observed with the more complex molecule when the spleen was
      eliminated. The response of the bone marrow to chemotactic stimuli, such as those
      have used, may be reflected in the general circulation, through an absolute
      increase of young neutrophilic leucocytes, within a period of less than 1 hour.
      Within this brief period there takes place maturation from Myelocyte C and
      metamyelocyte into the early motile leucocyte, and the delivery of these just
      matured cells into the circulation. The response to one injection of nucleinate
      or nucleotide may persist into the 3rd and 4th days with a gradual depletion of
      the normal reserve of Myelocytes C in the bone marrow.

PMID- 19869422
TI  - ALLERGIC IRRITABILITY : IV. THE CAPACITY OF GUINEA PIGS TO PRODUCE ANTIBODIES AS
      AFFECTED BY THE INHERITANCE AND AS RELATED TO FAMILIAL RESISTANCE TO
      TUBERCULOSIS.
AB  - The allergic irritability of closely inbred guinea pigs as represented by their
      capacity to produce hemolytic antibodies for beef and sheep corpuscles, and
      agglutinins for Bacillus typhosus and Bacillus abortus (Bang) differs by families
      and therefore is at least partly dependent on inherited characteristics. These
      differences show an imperfect but suggestive correlation with the differences in
      resistance of the same families to inoculation tuberculosis as previously
      determined by Wright and Lewis. The differences in antibody production also show
      an imperfect correlation with the differences in response in the anaphylactic
      reaction complex as previously determined by Lewis and Loomis. These studies
      suggest very strongly that the allergic irritability is one of the several
      inheritable characters which form a partial basis for the natural resistance to
      tuberculosis. The antibody-producing capacity is only satisfactorily defined when
      minimal or moderate amounts of antigen are used and this in single treatments.
      The irregularities in experimental result when repeated treatments or very large
      single treatments are used suggest that antibody production in the second or
      "acquired capacity" phase may rest on a somewhat different fundamental basis than
      the latent or potential natural capacity. There is some very slight evidence that
      production in the second phase may also be influenced by inherited qualities.

PMID- 19869423
TI  - ULCERATIVE TYPES AS DETERMINED BY INHERITANCE AND AS RELATED TO NATURAL
      RESISTANCE AGAINST TUBERCULOSIS: AN EXPERIMENTAL STUDY ON INBRED GUINEA PIGS.
AB  - Five families of strictly inbred guinea pig whose general resistance to
      experimental tuberculosis had previously been determined by Wright and Lewis have
      now been studied with reference to the characteristics of the local lesion
      produced by intracutaneous inoculation with the tubercle bacillus. It is found
      that there are clearly recognizable familial types based on the size and quality
      of the nodular lesion, the ulcerative lesion consecutive to this and the general
      effectiveness of the healing process when in evidence. Family 39 which has the
      lowest general resistance forms an initial papule which does not differ
      appreciably from that formed by Family 35 which is the most resistant. In the
      ulcerative stage Family 39 shows an indolent excoriating process which exhibits
      none of the qualities which would be expected to make for healing. Family 35
      exhibits a firm primary papule and nodule followed by an active healthy type of
      ulceration which is definitely restrained in comparison with that of the low
      resistance Family 13. Family 35 also presents the largest number of completely
      healed lesions in the later observation periods. Family 13 shows a larger,
      softer, primary papule and nodule than any of the others. The ulcer when formed
      is less restrained; that is, it is larger in proportion to the total size of the
      lesion. It is also more generally destructive. This family also shows a singular
      tendency to the formation of secondary ulcers along the lymphatic channels
      leading toward the adjacent lymph nodes. The adjacent lymph nodes are likewise
      more severely affected and frequently ulcerate through the skin giving rise to
      residual discharging sinuses. Families 2 and 32 are less definitely
      characterized. They are of the same order as 35 and 13 in that the ulcerations
      are active and healthy. Such similarities as are recognizable place Family 2 more
      nearly with 13 and Family 32 more nearly with 35. In general the qualities of
      lesion exhibited are such as to agree with the general resistance as previously
      determined and it is believed that the qualities underlying the tissue reaction
      may be safely considered to be among the influential factors in the make-up of
      the natural resistance against tuberculosis. The differences in reaction are in
      part manifested against agents causing simple inflammation also, and hence must
      be designated as non-specific with reference to the tubercle bacillus. There are
      definite indications of other "constitutional" differences in the character of
      the tissues and the general make-up of these families. The accumulated evidence
      from the study of the separate families and intercrosses between them is to the
      effect that the differences in question are transmitted by the blending type of
      inheritance and are therefore controlled by multiple unit characters. It is also
      suggested by the observations that certain of the significant characters are
      recessive in nature. It is of considerable interest that the observations agree
      very well with the older conception of an inherited, predisposing, constitutional
      diathesis as a significant factor in the incidence of tuberculosis.

PMID- 19869424
TI  - THE ANTIGENIC COMPLEX OF STREPTOCOCCUS HAEMOLYTICUS : II. CHEMICAL AND
      IMMUNOLOGICAL PROPERTIES OF THE PROTEIN FRACTIONS.
AB  - The chemical and immunological characteristics of the type-specific substance (M)
      of Streptococcus haemolyticus are considered. 1. A summary of the evidence for
      the protein nature of this substance follows: (a) It is precipiated by the usual
      protein precipitants such as, dilute alcohol, dilute acetic acid, and picric
      acid. (b) It contains 14 per cent protein nitrogen after considerable
      purification. (c) It is progressively destroyed by removal of the NH(2) group by
      treatment with nitrous acid. (d) It is completely and readily digested by trypsin
      and by pepsin. 2. "Purified" extracts react in relatively high dilution with
      homologous antibacterial sera, but do not precipitate most heterologous
      antibacterial sera or sera potent in non-type-specific antibodies for the group
      reactive nucleoprotein P or for the species-specific probable carbohydrate C.
      Attempts to immunize rabbits with the type-specific protein have been
      unsuccessful, with simple salt solution extracts of streptococci as well as with
      purified solutions. This protein seems, therefore, to have the characteristics of
      a haptene. The type-specific substance (M) is contrasted with the so called
      nucleoprotein (P) which shows group relationships with nucleoproteins of related
      species and is the only fraction of hemolytic streptococcus extracts so far
      obtained which, after separation from the bacterial cell, is a true antigen
      leading to antibody production when injected into rabbits. The occurrence of
      another non-type-specific protein (Y) is suggested by occasional cross-reactions
      of purified M with certain antibacterial sera. Since it has not been separated
      from extracts containing the type-specific M, little is known of it either
      chemically or serologically. The cross-reaction disappears on tryptic or peptic
      digestion of the extract. The fact that such extracts do not show cross-reactions
      with anti-P sera is evidence that this non-type-specific protein is not P.

PMID- 19869425
TI  - THE ANTIGENIC COMPLEX OF STREPTOCOCCUS HAEMOLYTICUS : III. CHEMICAL AND
      IMMUNOLOGICAL PROPERTIES OF THE SPECIES-SPECIFIC SUBSTANCE.
AB  - 1. The chemical and immunological characteristics of the species-specific
      substance (C) of Streptococcus haemolyticus are considered. (a) It seems to be a
      carbohydrate because considerably purified preparations of C resisted prolonged
      tryptic and peptic digestion and were negative for the ordinary protein color
      tests but gave positive Molisch reactions to the limit of the precipitin titer.
      One such "purified" lot, however, had 4.2 per cent nitrogen and only 28 per cent
      reducing sugars on hydrolysis. Whether the nitrogen was due to impurities or was
      combined in the C substance itself, as is true of the Type I pneumococcus
      specific polysaccharide, cannot be stated without more material. (b) The C
      substance forms precipitates with antibacterial sera prepared against
      heterologous, as well as against homologous hemolytic streptococci. These
      precipitates are typical discs like those formed by type-specific carbohydrates
      of other species of bacteria. C does not precipitate antinucleoprotein sera. (c)
      While there is only slight direct evidence that the C substance is not antigenic,
      there is considerable indirect proof that this is the case. It probably is a
      haptene in the sense of Landsteiner. 2. A discussion is included of the chemical
      and immunological relationships of all the serologically active substances so far
      identified in extracts of the hemolytic streptococcus.

PMID- 19869426
TI  - FURTHER OBSERVATIONS ON AN EXPERIMENTALLY PRODUCED SARCOMA OF THE CHICKEN.
AB  - Numerous attempts have been made by us to separate from the cells of a tar
      sarcoma of the chicken (Chicken Tumor 9) a causative agent for the growth.
      Experiments with filtrates and desiccates injected as such or in combinations
      with embryonic tissues have all failed to give positive results. So too have
      injections of filtrates and desiccates into developing chick embryos failed to
      yield a response. The results confirm those of previous work with the tumor in
      this laboratory. The growth would appear to differ in a fundamental respect from
      all tumors of the fowl previously studied.

PMID- 19869427
TI  - THE USE OF HISTAMINE AS A STANDARD TEST FOR DIMINISHED RESISTANCE IN
      SUPRARENALECTOMIZED RATS.
AB  - Of all the drugs thus far used in testing the resistance of suprarenalectomized
      rats, histamine has been found to be the most satisfactory. It is a readily
      obtainable and comparatively stable drug, producing characteristic symptoms. Its
      M.L.D. for a given strain of rats can be established within narrow limits, and
      the difference between the M.L.D. for normal and suprarenalectomized rats is
      comparatively great (1:20).

PMID- 19869428
TI  - LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS : IV. TYPE II
      PNEUMOCOCCAL MENINGITIS IN DOGS.
AB  - 1. With properly selected strains of Type II pneumococci, fatal meningitis may be
      produced by intrathecal infection in dogs. 2. The pathology of the disease
      differs from that produced by Type I pneumococci, at least with the strains
      employed. 3. Type II meningitis is characterized by early, very marked reactions,
      a very heavy fibrin exudation, and a tendency toward the rapid establishment of
      blocks. 4. Extreme vasodilatation and. hemorrhage are common. 5. The
      fibrinopurulent exudate tends to involve the walls and perivascular sheaths of
      deeply penetrating vessels, thereby causing thrombosis. 6. Thrombosis leads to
      foci of parenchymatous softening which, on subsequent infection, become brain
      abscesses. 7. The lateral venticles are a "point of election" for the luxuriant
      growth of pneumococci. Conversely there is evidence that Type II organisms tend
      somewhat to disappear from other regions, owing either to spontaneous
      phagocytosis or to filtration into the blood stream. The lateral ventricles,
      however, continually renew the supply. 8. Hydrocephalus occurs early-sometimes
      during the 2nd day of the disease. 9. Central myelitis is common and appears
      early in the disease. 10. Deep nerve cell lesions with necrosis and neuronophagia
      are encountered. Their pathology suggests a toxic source. 11. In most cases
      treatment has been impossible owing to severe early reactions, and only as a
      prophylactic has optochin-serum therapy any real value. It delays death, but has
      in no instance cured established disease in the dog. 12. Systemic generalization
      of Type II meningeal infection in the dog occurs, but it is rarely of sufficient
      extent to modify prognosis.

PMID- 19869429
TI  - THE PRODUCTION OF SKIN NECROSIS BY CERTAIN AUTOLYSATES OF PNEUMOCOCCUS (TYPES I
      AND II).
AB  - 1. Certain pneumococcus autolysates produce necrosis when injected into the skin
      of guinea pigs. 2. The necrosis-producing principle can be filtered through a
      Berkefeld N filter, is extremely thermolabile, and is very sensitive to
      oxidation. 3. The necrotizing poison can be separated from the pneumococcus
      hemotoxin by adsorption with red cells. This removes the hemotoxin and leaves the
      necrosis-producing principle unaffected. 4. The necrotizing substances obtained
      from Pneumococcus Types I and II are neutralized by the antiserum prepared with
      Pneumococcus I.

PMID- 19869430
TI  - CALCIUM AND INORGANIC PHOSPHORUS IN THE BLOOD OF RABBITS : I. RESULTS OF REPEATED
      AND PROLONGED OBSERVATIONS ON NORMAL RABBITS.
AB  - It will be seen at once that the mean values obtained for calcium are higher than
      most of those recorded in the literature, and that the values for inorganic
      phosphorus are perhaps lower. It is well to bear in mind, however, that the
      significance that may be attached to any series of determinations of calcium and
      inorganic phosphorus in the blood of animals depends largely upon the conditions
      under which the determinations are made. As is well known, there are many factors
      that may affect the values obtained, including inherent differences in the animal
      material and the method of analysis used as well as the particular procedure
      employed in carrying out a given method. When all other conditions are uniform,
      irregularities in the handling of the blood after it is drawn will give rise to
      surprisingly large differences in the results for both calcium and inorganic
      phosphorus, as permitting blood to stand tends to decrease calcium values and to
      increase those for inorganic phosphorus. It seems desirable, therefore, to
      emphasize the fact that the results recorded above are to be viewed as results
      obtained under certain definitely prescribed conditions which differ in several
      important respects from those governing determinations made by other workers in
      this field. Moreover, it is to be noted that the conditions varied to some extent
      with each of the 4 groups of animals comprising this series. For example, there
      was a small but definite age difference. The animals of Groups I and II were
      older and more mature than those of Groups III and IV at the beginning of the
      experiments, and this initial difference was increased by the extension of the
      experiments on Groups I and II over a longer period of time, so that the
      observations made on these animals not only included data for a more advanced
      age, but represented a mean age considerably above that of the observations made
      on the animals of Groups III and IV. There was a similar difference of
      experimental conditions between Groups III and IV, while the observations on
      Group II differed from those on Group I in that no blood analyses were made on
      the animals of Group II for 2 months after they were placed under observation.
      These particular features of the experiments are mentioned because an examination
      of the text-figures will show that a line of cleavage between Groups I and II on
      the one hand, and III and IV on the other, is traceable through all of the
      distribution curves and to some extent in the tabulated results. With the
      combined values as the axis of distribution, Groups I and II invariably hang
      together, or swing to one side, while Groups III and IV swing to the other.
      Moreover, the extreme positions are usually represented by Groups II and IV.
      Whether these peculiarities of the results are in reality attributable to the
      conditions mentioned or to some other cause, such as the length of cage life (2),
      or the particular period covered by the observations, the suggested relation is
      sufficient to indicate the extent to which even slight differences in
      experimental conditions may affect the results obtained for blood calcium and
      inorganic phosphorus. The values obtained for calcium may be regarded as showing
      a fairly close agreement (Tables I and II and Text-fig. 1). The extreme
      difference between the means for the 4 groups of animals is only 0.5 mg. or
      approximately 3.00 per cent of the mean for the combined groups. Still, the small
      absolute difference between the means for Groups I and IV is nearly 6 times its
      probable error and, hence, cannot be disregarded. The most important feature of
      these results is, however, the range of normal variation. The distribution curves
      (Text-fig. 1) show a remarkably close agreement in the frequency with which
      values of a given magnitude occurred and an unusually symmetrical distribution of
      all values. The coefficients of variation are comparatively small (7.09 to 8.9
      per cent), but values anywhere between 14.0 and 16.0 mg. of calcium per 100 cc.
      of serum occurred with great frequency, while figures as low as 13.5 or as high
      as 17.5 mg. (Table II) were by no means rare; and the extreme limits of
      observation indicate a potential difference in the calcium content of the blood
      of normal rabbits of as much as 100 per cent. Inorganic phosphorus was found to
      be subject to much wider variation than calcium (Tables III and IV and Text-fig.
      2). The coefficient of variation is approximately twice that for calcium (17.29
      and 8.01 respectively), while the group means for phosphorus show a difference of
      0.85 mg. per 100 cc. of serum. This difference is small in absolute value, but is
      nearly 20.0 per cent of the mean for all groups and is 15 times its probable
      error. It is safe to assume, therefore, that the values obtained indicate an
      actual difference in the inorganic phosphorus in the blood of the several groups
      of animals. This conclusion is borne out by the distribution frequencies (Table
      IV and Text-fig. 2) which show that the values obtained for Groups I and II lie
      at a distinctly lower level than those for Groups III and IV; the difference
      between modal classes is, in fact, of the same order as that shown by the means.
      The limits of probable variation as determined by the standard deviation of the
      combined results are 3.73 and 5.29 mg. per 100 cc. of serum, but one-third of all
      values lie outside of these limits, while the extreme limits of normal are
      sufficiently wide to include values that may differ by as much as 200.0 or even
      300.0 per cent. From the values obtained for calcium and inorganic phosphorus,
      the relation existing between the two substances may be measured in a number of
      ways. The ratio of the calcium to the phosphorus and the product of the amounts
      of the two substances have received the greatest attention. In addition to these
      values, we have computed values for the sum and for the ratio of the product to
      the sum, and also for the sum of the calcium-phophorus ratio and the product-sum
      ratio. The value for the sum of the calcium and inorganic phosphorus in the serum
      is determined largely by the calcium, but as it is also affected by the
      phosphorus, one might expect that the constancy of the value as compared with
      that of calcium would be diminished unless the variations in the two substances
      were so related as to neutralize each other. As is well known, there is an
      apparent tendency in this direction and in these experiments it was found that on
      the whole the values for the sum showed less variation (coefficients 6.42 and
      8.01 per cent) and were more uniformly distributed than those for calcium (Tables
      V and VI and Text-fig. 3). It is true that differences between groups were
      distinctly greater than in the case of calcium, but the agreement is sufficiently
      close to give evidence of a tendency to the maintenance of an inverse relation
      between serum calcium and inorganic phosphorus. Values for the product of calcium
      and inorganic phosphorus emphasize the phosphorus factor rather than the calcium,
      reversing the conditions that obtain in the case of the sum. A consideration of
      the product values given in Tables VII and VIII and Text-fig. 4 show that, while
      the order of variation is essentially the same as that of inorganic phosphorus
      (coefficients 17.09 and 17.29 per cent respectively), the distribution of values
      is more uniform. This may be attributable to the occurrence of coordinate
      variations in calcium and inorganic phosphorus. The situation presented by the
      values obtained for the ratio of calcium to inorganic phosphorus is somewhat
      surprising in that the ratio between the two substances proves to be less
      constant than the absolute amounts of either substance (Tables IX and X and Text
      fig. 5). There are considerable differences between the standard values for
      individual groups of animals, and the distribution frequencies are inclined to be
      irregular. Moreover, all groups show a large standard deviation and
      correspondingly high coefficients of variation, but combining the results for the
      4 groups of animals gives a fairly uniform and symmetrical distribution, a
      striking feature of which is the high frequency with which values occur over the
      entire range of standard variation, that is, from ratios of 2.85 to 4.29. It thus
      appears that, despite the evidence of a tendency to the observance of an inverse
      relation between the calcium and inorganic phosphorus in the blood, the ratio of
      one substance to the other is by no means constant. By using the product and the
      sum as a basis of expressing the relation between calcium and inorganic
      phosphorus, the form of the relation is ???

PMID- 19869431
TI  - CALCIUM AND INORGANIC PHOSPHORUS IN THE BLOOD OF RABBITS : II. RESULTS OF SINGLE
      DETERMINATIONS ON NORMAL RABBITS FROM RECENTLY ACQUIRED STOCKS.
AB  - Determinations of calcium and inorganic phosphorus were made on the blood of a
      large series of rabbits as they were received from the dealer for the purpose of
      determining whether results obtained under these conditions differed from those
      obtained by repeated observations on animals living in the laboratory. It was
      found that the results differed in the two cases, due largely to a decided
      difference in the inorganic phosphorus content of the blood; but the values for
      calcium were also affected.

PMID- 19869432
TI  - THE INTERCONVERTIBILITY OF "R" AND "S" FORMS OF PNEUMOCOCCUS.
AB  - 1. Single cell cultures of "R" pneumococci may revert in all respects to the "S"
      type. 2. In all instances in which reversion has occurred the "R" forms have
      invariably reverted to the same specific type from which they were originally
      derived. 3. The transformation "R" to "S" may be effected in vitro by growth in
      anti-"R" sera, as well as in vivo by the method of animal passage. 4. Reversion
      from "R" to "S" whether effected in vivo or in vitro, is always accompanied by
      the acquisition of maximal virulence.

PMID- 19869433
TI  - STUDIES UPON THE PHYSIOLOGICAL ACTION OF HEMATOPORPHYRIN.
AB  - THE RESULTS OF THESE OBSERVATIONS MAY BE BRIEFLY SUMMARIZED AS FOLLOWS: Feeding
      of hematoporphyrin to white mice over long periods of time produced no apparent
      changes in these animals and had no effect upon their sensitivity to light.
      Albino and slightly pigmented mice and rats injected with hematoporphyrin were
      protected from the rays of the sun by staining them a blue-black color with
      Verhoeff's hematoxylin. The dioxyphenylalanine (Dopa) reaction revealed no
      changes in the cutaneous pigment of animals injected with hematoporphyrin and
      exposed to sunlight, kept in the dark or diffused daylight. It was therefore
      assumed that the natural pigment of the skin plays only a physical role in
      protecting animals injected with hematoporphyrin from sunlight. Exposure to
      sunlight of only the intestine and mesentery of a cat under ether anesthesia,
      which had been injected with hematoporphyrin, was followed by death of the
      animal. Repeated injections into white mice of large amounts of blood from guinea
      pigs in hematoporphyrin shock failed to produce symptoms of hematoporphyrin
      shock. In a parabiosis experiment, one of a pair of white rats promptly developed
      characteristic symptoms and died when injected with hematoporphyrin and exposed
      to sunlight, while the other animal, which was protected from light, but whose
      circulation had been demonstrated to connect freely with that of its partner,
      showed no changes during the entire procedure. It has, therefore, been
      impossible, so far, to demonstrate any substance present in the blood of animals
      in hematoporphyrin shock which is capable of reproducing this condition in other
      animals when introduced into the circulation. Injection of hematoporphyrin
      followed by exposure of the entire animal to sunlight has been found to produce
      physiological changes in cats similar to those observed in traumatic shock. There
      promptly occurred a rapid fall of blood pressure to a very low level and marked
      lowering of body temperature. The venous blood was found to be poor in oxygen,
      rich in carbon dioxide and to show low carbon dioxide-combining power. The
      respiration, which first was accelerated, later on became deep and irregular. The
      reflexes and typical blood pressure responses to cutaneous and vagal stimulation
      could always be obtained until death. Marked diminution of oxygen and increase of
      carbon dioxide content were found to occur in mixtures of blood and
      hematoporphyrin exposed in vitro to sunlight. These changes in the blood,
      identical with those occurring in vivo during hematoporphyrin shock, support
      Gaffron's views regarding the effect produced by the combined action of
      hematoporphyrin and light, but do not further elucidate the nature of the manner
      in which such alterations take place. Unsuccessful attempts were made to produce,
      in both cats and dogs, physiological changes similar to those observed in
      hematoporphyrin shock by exposing only the blood flowing through a quartz glass
      cannula, connecting the femoral artery and vein, to strong arclight and sunlight.
      In another series of animals, which were first injected with hematoporphyrin,
      exposure of the circulating blood alone to arclight or sunlight did not produce
      hematoporphyrin shock, although the blood pressure did fall to an unusually low
      level in one instance. No changes were found to occur in the amount of non
      protein nitrogen, sugar or creatinine of the blood of animals in hematoporphyrin
      shock.

PMID- 19869434
TI  - RECIPROCAL EFFECTS OF CONCOMITANT INFECTIONS : I. THE INFLUENCE OF VACCINIA ON
      THE REACTION TO INFECTION WITH EXPERIMENTAL SYPHILIS.
AB  - Experiments are reported in which was studied the effect of a concomitant
      infection, vaccinia, upon the syphilitic reaction of rabbits. Vaccine virus was
      inoculated intracutaneously on the side of the body at the time of
      intratesticular inoculation with Treponema pallidum. The results showed clearly
      that the vaccination caused a profound disturbance in the syphilitic reaction,
      the ensuing syphilis being extremely severe. From an analysis of various features
      of the reaction, it appeared that the factor of host resistance was primarily
      concerned in the effects observed.

PMID- 19869435
TI  - CALCIUM AND INORGANIC PHOSPHORUS IN THE BLOOD OF RABBITS : III. PERIODIC AND
      PROGRESSIVE VARIATIONS IN NORMAL RABBITS.
AB  - Determinations of calcium and inorganic phosphorus were made on the blood of 5
      groups of normal animals over periods of 4 to 8 months. The material included
      animals from recently acquired stocks as well as animals that had been living
      under laboratory conditions for long periods of time. The results were analyzed
      with especial reference to the occurrence of periodic and progressive variations
      in the absolute amounts of calcium and inorganic phosphorus and the relations
      between the two substances. It was found that, among animals living in the
      laboratory, both calcium and inorganic phosphorus, as well as all expressions of
      the equilibrium between the two substances, exhibited a definite tendency to a
      progressive increase or decrease) as the case might be, and that clearly defined
      periodic variations occurred in all classes of animals. The progressive change
      was most marked in the case of inorganic phosphorus, the periodic change in the
      case of calcium, while both conditions were dearly shown by various expressions
      of the relation between calcium and inorganic phosphorus.

PMID- 19869436
TI  - THE ROLE OF CLASMATOCYTES AND CONNECTIVE TISSUE CELLS IN NON-SPECIFIC LOCAL
      CUTANEOUS IMMUNITY TO STAPHYLOCOCCUS.
AB  - 1. Plain broth is just as effective as specific broth filtrate if used as a skin
      compress for the protection of guinea pigs against a subcutaneous injection of
      Staphylococcus aureus. 2. Plain broth compresses applied for 48 hours previous to
      bacterial injection sometimes prevent the death of the animal and practically
      always alter the inflammatory reactions. 3. This protection is not specific and
      is localized to the area "compressed." 4. The protection lasts at least 24 hours
      after removal of the compress. 5. Broth compresses applied to the abdominal wall
      of a guinea pig for 48 hours produced definite histological changes, especially
      in the subcutis, i.e., edema, proliferation of clasmatocytes, thickening of the
      epidermis together with a moderate exudation of polymorphonuclears and small
      mononuclear cells. 6. The histological response to the subcutaneous injection of
      staphylococci was different in the control and the broth-prepared animal. 7. In
      the broth-prepared animal, there was an increase in clasmatocytes and fibroblasts
      with a dense exudation of polymorphonuclears, which latter, in the main, did not
      degenerate. The clasmatocytes phagocyted bacteria early and later engulfed the
      polymorphonuclears, while the fibroblasts rapidly walled off the lesion. The
      result was a localized abscess which either came to the surface and ruptured or
      was absorbed and organized.

PMID- 19869437
TI  - THE ELECTROPHORESIS OF THE BLOOD PLATELETS OF THE HORSE WITH REFERENCE TO THEIR
      ORIGIN AND TO THROMBUS FORMATION.
AB  - 1. The cataphoretic velocity of blood platelets (horse) in plasma has been found
      to be between 40 and 51 micro per sec. per volt per cm. The mean velocity
      obtained from five horses is . 45 micro per sec. per volt per cm. 2. The
      cataphoretic velocity of polymorphonuclear leucocytes in similar specimens is
      practically identical with that of the platelets. This is noteworthy because of
      the fact that lymphocytes and red cells have different speeds. 3. With
      spontaneous agglutination of platelets, white cells and red cells, there is no
      change in the cataphoretic velocity incidental to aggregation. 4. The possible
      surface composition of platelets and white cells is briefly discussed. 5. The
      bearing of these findings on the origin of blood platelets and the mechanism of
      thrombus formation is demonstrated.

PMID- 19869438
TI  - THE MODE OF SPREAD OF A FRIEDLANDER BACILLUS-LIKE RESPIRATORY INFECTION OF MICE.
AB  - A spontaneous respiratory disease of mice incited by Friedlander like bacilli has
      been described. The bacilli inducing the disease, while morphologically and
      culturally indistinguishable from the usual varieties of Friedlander bacilli, are
      antigenically distinct from the common type strains known. The bacilli grow
      better in cultures at 23 degrees C. than at 37 degrees C. The disease in mice
      displayed an incubation period of about 48 hours. About 50 per cent of an exposed
      population succumbed to septicemic and acute hemorrhagic, pneumonic processes.
      Among the exposed animals were some individuals which remained apparently well
      and carried the pathogenic bacilli in their nasal passages. The several
      manifestations of the spontaneous disease were reproduced by instilling small
      numbers of the cultured bacilli into the nasal passages. 48 hours after
      inoculation, certain mice had already succumbed; the deaths continued to occur,
      so that by the end of the 2nd week, 70-80 per cent of the animals had died. Among
      the survivors certain carriers of the bacilli in the nasal passages occurred; a
      few appeared entirely refractory to the infection. The succumbing mice showed at
      autopsy and by culture septicemia and diffuse pneumonic inflammation. No
      fluctuation in virulence could be detected in bacilli derived from mice while the
      disease was spreading spontaneously at the periods of epidemic rise,
      interepidemic interval, or postepidemic quiescence. Moreover, the bacilli
      cultured from the nares of apparently healthy carriers were equally pathogenic
      with those taken from the blood and lungs of animals succumbing quickly. No rough
      colony variants were cultured at any phase of the spontaneous disease, although
      they were readily obtainable by artificial culture. The variant strains proved
      stable and of low virulence. This Friedlander bacilli infection in mice takes
      several clinical courses, depending on variations in host reaction and not
      depending on bacterial variation. The particular type of infection manifested is
      determined by the degree of resisting power displayed by the infected animals at
      the moment that the infection occurred and progressed.

PMID- 19869439
TI  - IMMUNOLOGICAL STUDIES IN RELATION TO THE SUPRARENAL GLAND : I. HEMOLYSIN
      FORMATION IN NORMAL RATS.
AB  - Hemolysin formation was studied in normal rats. It was found that a single
      intraperitoneal injection of 1 cc. of a 10 per cent suspension of red blood cells
      results in an optimum high hemolysin titer 5 days after injection. The titer
      gradually falls, the hemolysin disappearing from 14 to 18 days after the
      injection. Larger amounts are less effective in the production of amboceptor.
      Much smaller amounts produce correspondingly lower hemolysin titers, although the
      ratio is not mathematically proportional. Repeated injections of 1 cc. of a 10
      per cent suspension of red blood cells at daily intervals or at intervals of 3 or
      5 days for three injections do not increase the hemolysin titer over that
      resulting from a single injection. Furthermore, the curve of antibody formation
      following a single small intraperitoneal injec tion of red blood cells is not
      altered by subsequent injections of similar amounts.

PMID- 19869440
TI  - IMMUNOLOGICAL STUDIES IN RELATION TO THE SUPRARENAL GLAND : II. HEMOLYSIN
      FORMATION IN SUPRARENALECTOMIZED RATS.
AB  - In a large series of suprarenalectomized rats, hemolysin formation, to a fixed
      amount of sheep cells injected intraperitoneally (1 cc. of a 10 per cent
      suspension), was studied 48 hours, 7, 14 and 28 days after operation. The
      hemolysin formation was studied in suprarenalectomized rats injected 2 weeks
      following the operation, with one-twentieth and ten times this amount. Hemolysin
      formation in rats traumatized by tearing the perisuprarenal tissue and injected 2
      weeks after the operation with 1 cc. of a 10 per cent suspension of sheep cells
      was studied and the results compared with those in the normal control rats. The
      effect of the operative procedure was controlled by removing one kidney in a
      series of rats and determining the antibody response to sheep cells. 1. Bilateral
      suprarenalectomy in rats subsequently injected intraperitoneally with 1 cc. of a
      10 per cent suspension of sheep cells resulted in a depression of hemolysin titer
      during 5 weeks following the operation, the depression being most marked during
      the 1st week. 2. Bilaterally suprarenalectomized rats injected intraperitoneally
      2 weeks after operation with 1 cc. of undiluted sheep cells gave hemolysin titers
      higher than did normal rats. 3. The quantity of antigen necessary to yield the
      maximum titer in suprarenalectomized rats 2 weeks after operation is ten times
      the quantity necessary to yield the same titer in normal rats. 4. Traumatization
      of the perisuprarenal tissue in rats produced the same effect on the antibody
      forming capacity as suprarenalectomy.

PMID- 19869441
TI  - AN EXPERIMENTAL STUDY OF DIATHERMY : V. THE ELEVATION OF TEMPERATURE IN THE
      PNEUMONIC LUNG.
AB  - 1. An experimental pneumonia with more or less lobar distribution has been
      produced in dogs by the method of intrabronchial insufflation of B.
      friedlaenderi, Type B, and Pneumococcus, Type I. 2. Such dogs as showed evidences
      of a pulmonary lesion when photographed by x-ray were selected for lung
      temperature measurements. 3. Measurements of lung temperature were made by means
      of thermocouples before and during diathermy. 4. The thermocouples which recorded
      the temperature in the consolidated lobes showed in most instances a more rapid
      rate of heating during diathermy than those in the normal lobes. The final
      increase in temperature in the pathological lobes over the normal lobes amounted
      to slightly more than 1 degrees C. 5. When local heating occurred during
      diathermy it was of the order of magnitude found in a lung in which the branch of
      the pulmonary artery supplying it had been clamped. 6. Histological examination
      of the lungs showed the pathological reaction to consist of intraalveolar exudate
      composed of polymorphonuclear leucocytes and desquamated alveolar epithelium. In
      some sections the exudate was sufficient to cause compression and emptying of the
      alveolar capillaries. 7. The local heating, we believe, depends upon this
      ischemic state of the smaller vessels. 8. Further evidence for an imparied
      circulation in the pneumonic lung is furnished by injection preparations in which
      the uninjected area corresponded exactly to the gross pathological lesion.

PMID- 19869442
TI  - ON INDIVIDUAL DIFFERENCES IN HUMAN BLOOD.
AB  - A clear-cut differentiation of human blood, aside from the blood groups, could be
      made by means of special agglutinating immune sera. The observations point to the
      existence of several agglutinable factors for which no agglutinins are
      demonstrable in normal human sera. In view of the latter circumstance the results
      reported do not imply any change in the scheme of the four blood groups. The body
      of serological evidence leads to the inference of a high degree of biochemical
      differentiation among individuals.

PMID- 19869443
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : X. LITMUS CONSTITUENTS AS
      VITAL STAINS: THEIR PREPARATION AND RELATIVE USEFULNESS.
AB  - We have devised methods for the separation and isolation of the important
      indicator constituents of litmus, azolitmin, and erythrolitmin, with a view to
      employing them as vital stains. Analysis of the color intensities of these dyes
      shows slight differences in them, azolitmin being the weaker pigment, weight for
      weight. Study of a third coloring matter, erythrolein, which exists in litmus has
      shown it to be an unsatisfactory indicator, and toxic for animals. Analyses with
      the spectrophotometer of the absorption of light by erythrolitmin and azolitmin,
      prepared by our methods, and tested over a wide acid-alkali range, show them to
      be pure substances, comparable in this respect with synthetic indicators. The
      errors in the interpretation of the indicator phenomena on vital staining, which
      are incident to changes in the concentration of the dyes, are so slight as to be
      negligible. The salt and protein errors on the other hand are large. The factors
      responsible for the Donnan equilibrium fail to influence the distribution of the
      indicators between fluid and gelatin. Erythrolein was found useless when employed
      for vital staining, and azolitmin proved unsatisfactory since it colors poorly
      and is toxic. But erythrolitmin can be used to great advantage. It is readily
      absorbed, and in non-toxic doses stains intensely. The range of pH at which it
      changes from red to blue fits it for the demonstration of changes in the reaction
      of living tissues. By reason, however, of the salt and protein errors to which it
      is liable, the pH cannot be accurately ascertained. Intravital staining with
      erythrolitmin yields results similar to those following injection of purified
      "whole litmus."

PMID- 19869444
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : XI. THE INTRACELLULAR
      REACTION OF THE KIDNEY EPITHELIUM AND ITS RELATION TO THE REACTION OF THE URINE.
AB  - The tubules of the mammalian kidney, vitally stained with erythrolitmin, show a
      significant color pattern, the cells of certain regions appearing bright blue and
      others brilliant red. The dye is segregated within the cytoplasm, staining fine
      granules diffusely. Under normal circumstances of renal function erythrolitmin is
      stored in the lining cells of the glomerulus and the epithelial cells of the
      proximal convoluted tubules in the blue, alkaline form. In the cells of the final
      portion of the distal convoluted tubules the dye is red. Between these regions a
      narrow transitional zone can be found, at times above, at times below the loop of
      Henle, in which the erythrolitmin-stained granules in the tubule cells are
      violet, or red and blue within the same cell. Alterations in the relative
      reaction of certain regions of the tubules, as disclosed by the color of the dye
      within the cells, can be induced by means that alter the reaction of the urine.
      When acid urine is being secreted there is a change from relative alkalinity to
      acidity high up in the tubular canal, in the proximal convoluted tubules. During
      the secretion of markedly alkaline urine the intracellular granules appear blue
      most of the way down the tubular canal, even to the first portion of the distal
      convoluted tubules. When the urine is neutral the cells above the descending limb
      of the loop of Henle are alkaline to erythrolitmin, and those below this point
      appear acid. The granules within the endothelial cells of the glomerulus and the
      epithelial cells of the first portion of the proximal convoluted tubules are
      always alkaline to erythrolitmin; while those within the cells of the final
      portion of the distal convoluted tubules are always acid regardless of the
      reaction of the urine. Only after complete suppression of urine as result of
      massive doses of acid do granules of the sort first mentioned manifest the color
      indicative of acidity. The interpretation of the findings waits upon further
      work.

PMID- 19869445
TI  - ETIOLOGY OF OROYA FEVER : XII. INFLUENCE OF MALARIAL INFECTION (PLASMODIUM
      INUI?), SPLENECTOMY, OR BOTH, UPON EXPERIMENTAL CARRION'S DISEASE IN MONKEYS.
AB  - The experiments reported were designed to determine the influence of malarial
      infection (Plasmodium inui?), splenectomy, or both combined, upon the course and
      character of experimental infection with Bartonella bacilliformis in monkeys
      (Macacus rhesus and M. cynomolgus). Blood withdrawn from a monkey showing
      spontaneous malarial infection was inoculated intravenously into monkeys (a) 1
      month prior to inoculation with virulent verruga material, (b) simultaneously
      with the verruga material, and (c) during convalescence from verruga infection of
      moderate severity. All the monkeys contracted the malarial infection and suffered
      one to three paroxysms during a period of about a month. The verruga lesions
      appeared in the inoculated animals in due course, were of average size, remained
      for the usual length of time, and Bartonella bacilliformis was recovered in
      culture from blood which also contained the plasmodia. The lesions in the
      convalescent animals continued to heal at the normal rate, and blood cultures
      were negative for Bartonella bacilliformis, as is usual during convalescence. One
      of the recovering animals was reinoculated with virulent verruga material a month
      after the injection of the malarial blood, but neither did new lesions arise nor
      old ones recur. The malarial infection, therefore, had no effect upon the course
      of verruga or upon the establishment of immunity to Pattonella bacilliformis,
      hence it would appear that malaria and verruga may coexist in the same individual
      without unfavorable effect of one disease upon the course of the other.
      Similarly, splenectomy led to no appreciable aggravation of Bartonella infection.
      One monkey subjected to splenectomy and inoculated with verruga material shortly
      afterwards had an unusually severe reaction, but another, which was infected with
      material from the first and simultaneously splenectomized, reacted only
      moderately, while the non-splenectomized control showed a severer type of
      cutaneous infection. Even the combination of splenectomy and malarial infection
      did not appreciably aggravate the experimental verruga. Neither relapse of
      verruga nor reinfection with Bartonella bacilliformis was induced in convalescent
      or recovered monkeys as a result of splenectomy.

PMID- 19869446
TI  - PHOTOSENSITIZATION OF ANIMALS AFTER THE INGESTION OF BUCKWHEAT.
AB  - THE CHIEF POINTS PRESENTED IN THIS PAPER ARE: 1. Following the ingestion of
      buckwheat (plant or seed) varicolored guinea pigs, white swine and goats
      exhibited symptoms of photosensitization, the degree of sensitization being in
      the order given. 2. Rabbits, dogs, white mice and rats did not manifest symptoms
      of photosensitization. 3. The symptoms and reactions were: agitation, itching,
      scratching of the ears, weakness, urticaria with sloughing and symptoms similar
      to those in anaphylaxis. 4. Microscopic examinations showed the lack of marked
      pathologic change. The lesions, such as petechial hemorrhage of the lungs, brain,
      liver, stomach and kidneys, suggest that profound toxemia has been present. 5.
      Lesions were not found which appeared to be suggestive of malignant neoplasms. 6.
      Irradiation by a quartz mercury vapor lamp apparently develops a resistance to
      photosensitization, probably because of increased pigmentation induced by ultra
      violet light. 7. From the nature of the physiologic and pathologic reactions
      produced under various filters and from a consideration of the percentages of
      transmission of solar energy in the visible spectrum, it would seem that the
      region of photosensitization lies between 580 millimicrons (yellow) and the red
      end of the spectrum. This conclusion, moreover, is substantiated by the fact that
      irradiation by a quartz mercury vapor lamp (which radiates no energy in the
      visible spectrum at a wave-length greater than 579 millimicrons) produces no
      symptoms or reactions. 8. Spectrophotometric determinations of alcoholic extracts
      of grass (non-toxic) and of buckwheat (toxic) show the presence of two additional
      bands in the absorption spectrum of buckwheat with maxima at about 540 and 600
      millimicrons, respectively, together with the common absorption zones at 430 to
      490 millimicrons and 630 to 690 millimicrons. 9. Spectrophotometric
      determinations of blood serums of sensitized animals show, besides the usual
      absorption bands peculiar to oxyhemoglobin (with maxima at 540 and 580
      millimicrons respectively), two zones with maxima at 600 and 660 millimicrons
      respectively. 10. The fluorescence of chlorophyll per se, as suggested by
      previous investigators, is not, in all probability, the cause of the
      sensitization induced by buckwheat. 11. Hematoporphyrine is not the photodynamic
      substance in all probability. 12. Phylloporphyrine may be the photodynamic
      substance. In this regard, also, the possibility of cholehematin is not to be
      ruled out.

PMID- 19869447
TI  - EXPERIMENTS ON THE VISIBILITY OF THE POLYHEDRAL VIRUSES.
AB  - With the techniques employed we have not been able to detect any qualitative
      differences between the particles visible in normal blood and in blood from cases
      of wilt disease and grasserie. Of the two conditions we can speak more definitely
      in the case of grasserie, because this we have studied quantitatively as well,
      that is to say, the particles visible microscopically and ultramicroscopically
      have been counted without bringing to light any marked difference between normal
      and diseased blood. This leads us to believe that the virus of wilt disease is
      probably invisible, and the virus of grasserie almost certainly so, when studied
      with the optical equipment that we have used, and that further evidence will be
      necessary before one can accept the chlamydozoa or the Borrellina as the active
      etiological agents. Although these two polyhedral viruses do not appear to be
      visibly particulate, it does not follow that other alterable viruses are not
      organized in this way. Each should be considered on its own merits.

PMID- 19869448
TI  - EFFECT OF FORMALIN ON THE VIRUS OF VESICULAR STOMATITIS OF HORSES.
AB  - The virus of vesicular stomatitis is not readily killed by formalin. This
      chemical is one of a group which coagulates the proteins of the medium in which
      the virus is usually contained. It has already been found(7) that other reagents
      of the protein-coagulating group are not actively virucidal) and the effect of
      formalin in this instance is therefore characteristic of the group. The so called
      formalinized vaccines which give rise to immunity can be shown to have done so
      because of the presence of living virus. A single injection of such so called
      "vaccine," or of other material containing living virus, is capable of inducing
      immunity in guinea pigs. No protection, however, follows a single injection of
      dead virus. Furthermore, repeated inoculations of virus killed by formalin
      likewise fail to induce resistance against subsequent injections of the living
      virus. It is concluded, with respect to the virus of vesicular stomatitis, that
      the use of formalin has failed to solve the problem of active immunization with
      dead virus.

PMID- 19869449
TI  - THE ANTIGENIC COMPLEX OF STREPTOCOCCUS HAEMOLYTICUS : IV. ANAPHYLAXIS WITH TWO
      NON-TYPE-SPECIFIC FRACTIONS.
AB  - The anaphylactic reactions of two non-type-specific fractions of hemolytic
      streptococcus extracts parallel the precipitin reactions. The nucleoprotein, P,
      is a true antigen, in that it stimulates antibody production in rabbits, as shown
      before, and produces anaphylactic shock in guinea pigs actively as well as
      passively. The probable carbohydrate, C, on the other hand, does not induce
      antibody formation in rabbits, so far as known at present, but does produce
      typical anaphylactic shock in guinea pigs passively sensitized with antibacterial
      serum provided the serum shows a high titer of C precipitins. This is an instance
      of a hapten, probably carbohydrate in nature, causing anaphylactic shock in
      passively sensitized guinea pigs.

PMID- 19869450
TI  - THE ANTIGENIC COMPLEX OF STREPTOCOCCUS HAEMOLYTICUS : V. ANAPHYLAXIS WITH THE
      TYPE-SPECIFIC SUBSTANCE.
AB  - 1. Type-specific anaphylactic shock was produced with HCI extracts of
      Streptococcus haemolyticus in guinea pigs passively sensitized with antibacterial
      sera. 2. With occasional sera and certain HCl extracts, type-specific shock was
      not produced unless the serum was first absorbed with heterologous bacteria or
      unless the guinea pigs were desensitized with heterologous extracts before
      testing with the homologous extract. The findings indicated that this was due to
      the presence of the non-type-specific substance which has been provisionally
      designated as Y. 3. Tryptic digestion destroyed the ability of HCI extracts
      containing the type-specific M substance and the non-type-specific Y substance to
      produce anaphylactic shock in passively sensitized guinea pigs. 4. Active
      sensitization was not accomplished with the type-specific M. It seems probable,
      therefore, that this substance is a hapten, reacting with antibodies but not
      stimulating their production after separation from the bacterial cell.

PMID- 19869451
TI  - THE PROPERTIES OF THE BACTERICIDAL SUBSTANCE IN MILK.
AB  - Certain of the properties of the bacterial agent in milk have been studied. The
      substance is present in the colostrum and milk of the first few days of lactation
      as well as later. Its concentration varies in the secretion from various quarters
      of the same cow. Its activity is diminished by heat and cannot be restored again
      by the addition of active milk. The principle is present in whey and readily
      passes through the coarsest Berkefeld filter although a considerable portion is
      retained by N candles. The finest filter (W) completely retains it. It is
      adsorbed by animal charcoal but not by kaolin, kieselguhr, or bolus alba. It can
      be desiccated and its presence has been demonstrated in one brand of dried milk.

PMID- 19869452
TI  - BACTERIAL VARIATION IN CULTURES OF FRIEDLANDER'S BACILLUS.
AB  - 1. Under proper conditions mass R cultures of Friedlander's bacillus may give
      rise to a number of variants which are dissimilar in colony appearance and
      morphology. Three such forms have been described. In two varieties, differences
      have been observed not only in colony formation and morphology, but also in
      cultural and antigenic characters. 2. None of the methods employed were adequate
      to cause reversion of any of the R variants to the S type. Growth of the R2
      variant in its own antiserum, however, induced a change to the R1 form. 3. R
      forms of Friedlander's bacillus may be derived from S strains by aging or by
      growth in anti-S serum of the homologous type. 4. R strains may be isolated in
      culture directly from infection. In the cases where R forms were found, S cells
      were also present, and the pathological condition was of a chronic nature.

PMID- 19869453
TI  - IS THERE AN IMMUNOLOGICAL RELATIONSHIP BETWEEN HORSE SERUM AND HORSE DANDER?
AB  - Evidence has been submitted of the existence of a common antigenic substance in
      horse dander and horse serum. This evidence has been derived from three lines of
      study: (a) Cross-precipitation tests involving (1) the titration of antisera
      against horse serum with saline extract of horse dander and (2) titration of
      antisera against horse dander with normal horse serum. (b) Cross-anaphylactic
      tests by the uterine strip method of Dale. (c) Cross-anaphylactic tests in living
      guinea pigs by the usual shock method. It seems likely from the work here
      described that the common antigen is present in small proportion in horse dander.
      Its concentration in horse serum is not indicated by the results obtained.

PMID- 19869455
TI  - STUDIES ON IMMUNOLOGICAL RELATIONSHIPS AMONG THE PNEUMOCOCCI : II. A COMPARISON
      OF THE ANTIBODY RESPONSES OF MICE AND OF RABBITS TO IMMUNIZATION WITH TYPICAL
      TYPE III PNEUMOCOCCI AND TO IMMUNIZATION WITH A RELATED STRAIN.
AB  - The paper reports an experimental comparison of the antibody responses of mice
      and of rabbits to immunization with typical Type III pneumococci and a strain
      related to Type III. The results as a whole show that the relative antigenic
      effectiveness of these two kinds of related pneumococci, is different in
      different animals. In rabbits the strain related to but not identical with Type
      III elicits the better response; in mice, the typical Type III strain is more
      effective. These relationships furnish an example of the influence of the species
      of animal upon the effectiveness of even closely related bacterial antigens.

PMID- 19869454
TI  - STUDIES ON IMMUNOLOGICAL RELATIONSHIPS AMONG THE PNEUMOCOCCI : I. A VIRULENT
      STRAIN OF PNEUMOCOCCUS WHICH Is IMMUNOLOGICALLY RELATED TO, BUT NOT IDENTICAL
      WITH TYPICAL STRAINS OF TYPE III PNEUMOCOCCI.
AB  - The paper reports a study of a virulent, S-producing strain of Pneumococcus which
      is immunologically related to, but not identical with typical strains of Type III
      pneumococcus. In a potent anti-Type III serum, the relationship of this strain to
      typical Type III strains appears to be about the same as the relationship of
      Avery's Subgroup Type II strains to typical Type II. But a more pronounced
      distinction is evident in the antiserum produced by immunization with the strain
      related to Type III. This antiserum contained antobodies specifically reactive
      with typical Type III bacteria as well as antibodies reactive with the homologous
      strain, while anti-Subgroup Type II immune sera are devoid of antibodies reactive
      with typical Type II pneumococci. The result of absorption experiments were the
      same as those usually obtained with immunologically related, but not identical
      bacteria. The failure of reciprocal absorption and the marked variations in the
      relative potencies of the antiserum from different individual animals might be
      presented as presumptive evidence that two different anti-S antibodies are
      contained in Type III immune horse serum. The theoretical significance of
      virulent pneumococci which are related to but not identical with the "fixed"
      types, is discussed from the standpoint of their importance in the biological
      classification of the Pneumococcus group.

PMID- 19869456
TI  - UDDER INFECTION WITH STREPTOCOCCI OF THE SCARLET FEVER TYPE : I. SPONTANEOUS AND
      EXPERIMENTAL UDDER INFECTION.
AB  - The clinical and bacteriological findings in two cows the udders of which became
      infected under natural conditions with hemolytic streptococci of the scarlet
      fever type are discussed. One of the cows was found in a herd supplying raw milk
      to a small town where a milkborne outbreak of scarlet fever had occurred a short
      time before. When small numbers of the streptococcus obtained from this case were
      injected into the udder of a normal cow severe mastitis accompanied by a well
      marked general reaction resulted. Evidence leads to the conclusion that a severe
      attack of mastitis due to this organism in one quarter does not sufficiently
      immunize the other quarters to protect them completely since the streptococcus
      can be readily implanted in them. The secondary infections were much milder than
      the original process.

PMID- 19869457
TI  - UDDER INFECTION WITH STREPTOCOCCI OF THE SCARLET FEVER TYPE : II. A STUDY OF THE
      SCARLET FEVER TYPE OF STREPTOCOCCI ISOLATED FROM THE UDDER OF THE COW.
AB  - The streptococcus isolated from the udder of a cow on a farm where an outbreak of
      scarlet fever originated has been correlated with known scarlet fever strains.
      This streptococcus and another also isolated from the udder of a cow are
      indistinguishable in cultural characters and certain antigen affinities from S.
      scarlatinae. Skin tests indicate that the strain isolated from the milk of the
      cow in a herd to which the scarlet fever epidemic was attributed produced a toxin
      which was neutralized with scarlet fever antitoxin.

PMID- 19869458
TI  - UDDER INFECTION WITH STREPTOCOCCI OF THE SCARLET FEVER TYPE : III. THE INFLUENCE
      OF MILK ON THE GROWTH OF SCARLET FEVER STREPTOCOCCI.
AB  - The experiments indicate that milk filtered through a Berkefeld candle V or
      heated at 58 degrees C. for 20 minutes when added to blood agar plate cultures
      interferes with the development of colonies of the scarlet fever streptococcus.
      The observed inhibition is proportional to the amount of milk. When the
      approximate milk dilution in the Petri dish is 1:20 or 1:25 growth of the
      organisms is completely suppressed or only a small proportion of non-hemolytic
      colonies develop. As the amount of milk is decreased the colonies become larger
      and their hemolytic zones more pronounced, although even when the final dilution
      of milk reaches 1:100 or 1:125 only colonies easily mistaken for the narrow zoned
      bovine streptococci appear. The effects upon the surviving organisms would appear
      to be transient since both the non-hemolytic colonies and those with small zones
      manifest the original hemolytic properties when transferred to other media. When
      scarlet fever streptococci are added in small quantities to milk heated at 58
      degrees C. for 20 minutes and incubated growth is inhibited. If the period is
      prolonged the streptococci are killed. On refrigeration of such mixtures some of
      the streptoccci are killed but others survive the test period.

PMID- 19869459
TI  - THE REGENERATION OF AUTOPLASTIC LYMPH NODE TRANSPLANTS.
AB  - The reticulum plays an important part in the regeneration of lymph nodes
      autoplastically transplanted into the abdominal wall of the albino rat. The
      necrosis which follows transplantation involves mainly the lymphocytes. A margin
      of lymphocytes is preserved only at the periphery. This may be due to early
      lymphatic connection with the marginal sinus of the node. The reticulum cells are
      apparently more resistant since for the most part they do not degenerate. There
      are three possible origins of the lymphocytes of the regenerated node. They may
      arise by proliferation of lymphocytes retained at the periphery of the plant. The
      presence of a few mitotic figures among lymphocytes in the marginal region
      confirms the possibility of this mode of origin. They may also be derived from
      lymphocytes brought into the transplant by the blood or lymph circulation. Though
      some lymphocytes are present in the marginal sinus, and an occasional lymphocyte
      is seen in the capillaries which enter at the hilus, we believe that this source
      of origin of the lymphocytes is negligible. On the other hand, the hyperplastic
      reticulum appears to be the important source of lymphocyte production. These may
      be derived from the reticulum directly as small lymphocytes, or may be formed
      through the intermediary stage of large lymphoid cells. This capacity is not
      limited to lymphatic reticulum, as small foci of lymphocyte formation are found
      in the connective tissue in the vicinity. of the transplants. The reticular
      origin of lymphoctes is most easily observed in the earlier stages of
      regeneration before the picture is obscured by the numerous small lymphocytes.
      Two structures in the regenerating node are directly traceable to the same
      structures of the transplanrt. These are the marginal sinus and the hilus. The
      marginal sinus of thef transplant is preserved, and is probably an important
      means by which lymphatic communication is established with the surrounding
      tissue. The hilus is the site of entry of the blood vessels, and the hilus of the
      regenerated node is the same as that of the transplant.

PMID- 19869460
TI  - THE AUTOPLASTIC TRANSPLANTATION OF TISSUES INTO THE BONE MARROW CAVITY : I. THE
      THYMUS.
AB  - When the thymus is autoplastically transplanted into the marrow cavity of the
      tibia of a guinea pig, the transplant degenerates, regenerates, and finally
      atrophies. The degeneration and regeneration of the thymus when so transplanted
      are similar to the homologous changes occurring when it is autoplastically
      transplanted into the abdominal wall. For comparative study the material used in
      previously published work on transplantation into the abdominal wall was
      reviewed. A difference in the final result of transplantation of thymus in these
      two situations is observed. In the abdominal wall the thymus regenerates and
      persists apparently indefinitely. Abdominal wall thymus transplants more than a
      year old have been observed. In the bone marrow cavity, the regeneration, which
      is slower and less abundant, is followed by an atrophy of the gland, and finally
      its complete disappearance. This atrophy is, we believe, the result of the
      encasement of the thymus in a bony capsule. That the genetic character of the
      transplanted tissue has much to do with the success of the transplantation in the
      marrow, is evident from the fact that some other tissues regenerate without
      encapsulation, even though they may finally disappear. The blood clot about the
      thymus which fills the rest of the curetted cavity, is quickly vascularized and
      replaced by regenerated cellular bone marrow and newly formed bony trabeculae.
      The difference in the fate of the thymus when transplanted in the abdominal wall
      and in the marrow, is probably due to difference in the reciprocal relations of
      the thymus to the tissue in those situations. From experience gained in the
      transplantation of other tissues into the marrow cavity, we have learned that
      encapsulation of the transplant does not occur with all tissues. The reaction of
      the marrow to transplanted thymus is similar to its reaction to any tissue
      foreign to it.

PMID- 19869461
TI  - SURFACE TENSION OF SERUM OF THE SENSITIZED GUINEA PIG : I. SURFACE TENSION
      CHANGES INCIDENT TO THE PROCESS OF SENSITIZATION.
AB  - The change in surface tension behavior in the serum of sensitized guinea pigs is,
      as du Nouy has concluded for immunized rabbit serum, not referable to an antibody
      content, since we know that the capacity for transfer of sensitization remains in
      the serum indefinitely, while the increased time-drop phenomenon is a transitory
      manifestation. That this phenomenon cannot be invoked by a new antigen capable of
      calling out its specific antibody would seem to make this response one due to
      some basic stable alteration of a tissue active in the general process of
      sensitization: That this alteration is not one called out by such a simple toxic
      injury as a uranium nitrate nephritis is contributory evidence that the primary
      toxicity of the horse serum is not the specific factor involved.

PMID- 19869462
TI  - SURFACE TENSION OF SERUM OF THE SENSITIZED GUINEA PIG : II. SURFACE TENSION
      CHANGES IN THE BLOOD IN ANAPHYLACTIC SHOCK.
AB  - The primary change in surface tension of serum incident to anaphylactic shock is
      probably due to a lowering of the surface tension of the serum by the addition of
      the antigen serum. But this may be followed by further decrease or by an increase
      depending on the intensity and duration of certain secondary tissue changes.

PMID- 19869463
TI  - THE PATHOGENESIS OF EARLY OBSTRUCTIVE JAUNDICE.
AB  - 1. After experimental ligation of the bile ducts in dogs, two distinct processes
      are clearly manifested: first, the accumulation of the normally circulating
      bilirubin in the blood with its characteristic indirect Van den Bergh reaction
      for a period of several hours, and second, the subsequent appearance of the bile
      bilirubin giving the direct Van den Bergh reaction. It is possible that the first
      process may be due to a temporary reflex inhibition of the function of the liver
      cells due to ligation of the duct and comparable to the same phenomenon which
      usually occurs in the kidney when the ureter is ligated. The second process
      begins before any rupture of the bile capillaries is visible. Liver sections made
      6 to 7 hours after obstruction show these bile capillaries dilated and extending
      between the liver cells in small distended pouches the blind end of these lying
      in contact with the pericapillary spaces. It is possible that bile may diffuse
      from these thin walled pouches into the perivascular lymph spaces, this diffusion
      being favored by the mounting pressure inside the bile ducts. 2. In early
      obstructive jaundice bile first appears in the lymph, but exclusion of the
      thoracic duct from the circulation by drainage causes a delay of only a few hours
      in the appearance of bile bilirubin in the blood stream. We must therefore
      conclude that after biliary obstruction bile enters the circulation both by way
      of the blood capillaries and the lymphatics, although the latter route is the
      more important.

PMID- 19869464
TI  - EXPERIMENTAL INTRADERMAL PNEUMOCOCCUS INFECTION IN RABBITS.
AB  - 1. The intradermal inoculation of rabbits with Type I pneumococci gives rise to a
      local lesion and a definite sequence of other events that offer many analogies to
      pneumococcus lobar pneumonia, and for this reason the condition is being employed
      for a resurvey of the subject of pneumococcic infection. 2. This symptom-complex
      has been described in detail particularly as to the development of the local
      lesion, the temperature reaction, the bacteriemia, the white count, the
      persistence of organisms in the lesion, and the development of protective
      substances. 3. A certain number of animals recover from this condition after a
      definite course and by a process spoken of as crisis. The events correlated with
      this crisis have been described. 4. If sufficient antipneumococcic serum is given
      intravenously at 24 hours, prompt recovery can be brought about. The essential
      points of this recovery have been established. 5. Within 5 days after a single
      vaccination with dead pneumococci the normal rabbit develops an immunity to
      infection. If the rabbit is vaccinated and then infected within the period
      necessary for the development of this immunity the course of the consequent
      disease is shortened in proportion to the interval between vaccination and
      infection.

PMID- 19869465
TI  - THE FUNDAMENTAL PROPERTIES OF THE FIBROBLAST AND THE MACROPHAGE : III. THE
      MALIGNANT FIBROBLAST OF SARCOMA 10 OF THE CROCKER FOUNDATION.
AB  - 1. A pure strain of fibroblasts has been isolated from Sarcoma 10 of the Crocker
      Foundation. After about 16 months of life in vitro, the malignancy of the strain
      is as great as that of the original tumor. 2. The strain has been compared with a
      strain of normal rat fibroblasts. The malignant cells are generally larger,
      coarser, and more refringent than normal cells. They possess all the
      morphological characteristics of fibroblasts. They do not show any abnormalities
      and never degenerate and die. They are to all appearances healthy cells. Their
      mode of locomotion is identical with that of normal fibroblasts. Their colonies
      are larger, but the architecture is similar. 3. The residual activity of both
      cell types, the duration of their life, and their rate of growth in a nutrient
      medium are almost identical. 4. The sarcomatous fibroblasts liquefy a rat plasma
      coagulum while normal fibroblasts do not. They turn phenol red golden yellow
      whereas, under the same conditions, normal cells turn it pinkish orange. 5.
      Sarcomatous and normal fibroblasts of the rat multiply to an unlimited degree in
      chick embryo juice. They live for only a short time in rat serum and chick serum.
      Calf liver digest will suffice for an unlimited proliferation of sarcoma
      fibroblasts, but fails to support the life of normal fibroblasts for very long.
      6. The presence of bone marrow greatly increases the rate of growth of
      sarcomatous fibroblasts cultivated in rat serum, while it only slightly affects
      that of the normal cells. The unlimited growth of the sarcomatous tissue in
      animals to which it is transplanted may be attributed to the presence of
      macrophages, which are a normal constituent of the tumor, and possibly are a
      necessary factor of its growth in vivo.

PMID- 19869466
TI  - RECIPROCAL EFFECTS OF CONCOMITANT INFECTIONS : II. THE INFLUENCE OF VACCINAL
      IMMUNITY ON THE REACTION TO EXPERIMENTAL SYPHILIS.
AB  - Experiments are reported in which it was shown, first, that the effectiveness of
      the reaction to experimental syphilis was increased in rabbits immune to vaccine
      virus, the ensuing disease being less severe than in control animals. It was
      further shown that a comparable modification of the syphilitic reaction occurred
      in rabbits inoculated intratesticularly with a mixture of Treponema pallidum and
      vaccine virus, and it was suggested that this result was due to the influence of
      a vaccinal immunity and to the local effect of the vaccinal reaction. It was
      pointed out that the manner in which two concomitant experimental infections are
      induced is of significance in determining the character of the host's reaction.

PMID- 19869467
TI  - THE INCUBATION PERIOD OF YELLOW FEVER IN THE MOSQUITO.
AB  - 1. The yellow fever virus was found in infectious form in Aedes aegypti
      throughout the entire period of the extrinsic incubation, as demonstrated by the
      injection of the bodies of mosquitoes into normal rhesus monkeys at daily
      intervals after the insects had fed on an infected animal. 2. The virus was
      transmitted through the bite of the mosquitoes, in one experiment on and after
      the 9th day, and in two experiments on the 12th day after the initial infecting
      feed. 3. The pathologic changes produced by the injection of the infected
      mosquitoes into normal monkeys during the extrinsic incubation were in every
      respect those of typical experimental yellow fever. 4. The monkeys withstand
      easily the subcutaneous injection of the mosquito emulsion. No acute inflammatory
      reaction was observed at the site of injection in any of the seventeen animals
      inoculated with this material in these three experiments.

PMID- 19869468
TI  - CHOLESTEROL AND CHOLESTEROL ESTER CONTENT OF BOVINE COLOSTRUM.
AB  - The total amount of cholesterol found in colostrum and milk is comparatively low.
      The amount of cholesterol found in colostrum declines at an ever decreasing rate
      as milk secretion develops until at 48 hours the cholesterol is nearly the same
      as that found in milk 3 months or 7 months after parturition. The morning milk
      differs from the evening milk in that the cholesterol bound as ester is greater
      in amount.

PMID- 19869469
TI  - CHOLESTEROL AND CHOLESTEROL ESTER IN THE BLOOD SERUM OF CATTLE LATE IN PREGNANCY
      AND DURING THE EARLY LACTATION PERIOD.
AB  - 1. The total cholesterol and cholesterol ester of bovine blood serum during the
      "dry" period of late pregnancy is low. 2. Following parturition the total
      cholesterol and cholesterol ester of bovine blood serum show a still greater,
      very transient decrease followed by a gradual rise to reach a rather constant
      level 40 to 50 days post partum. This lactation level is very much higher than
      the "dry" level.

PMID- 19869470
TI  - INFLUENCE OF LIGHT ENVIRONMENT ON THE GROWTH AND NUTRITION OF NORMAL RABBITS WITH
      ESPECIAL REFERENCE TO THE ACTION OF NEON LIGHT.
AB  - The influence of light environment on the growth and nutrition of normal rabbits
      was studied by comparing the weight curves of animals living under different
      environmental conditions for periods of 4 to 8 months and the effects of change
      from one environment to another. Prolonged exposure to neon light was compared
      with confinement in the dark and exposure to diffuse, filtered sunlight of
      varying intensity. The results of the experiments showed that growth and
      nutrition were greatly affected by the light environment in which the animals
      lived. The effects produced by a given environment varied with the color or breed
      of the animal and appeared to be out of proportion to the differences in the
      intensity of the light or the energy represented.

PMID- 19869471
TI  - INFLUENCE OF LIGHT ENVIRONMENT ON THE GROWTH OF HAIR IN NORMAL RABBITS WITH
      ESPECIAL REFERENCE TO THE ACTION OF NEON LIGHT.
AB  - In a series of experiments dealing with the influence of light environment on
      normal rabbits, the growth of hair over shaved areas was used as an index of
      functional activity. The conditions compared were exposure to neon light,
      complete exclusion of light, and exposure to diffuse, filtered sunlight of
      varying intensity. It was found that prolonged existence under these conditions
      affected the proliferative activity of hair follicles in a manner and to an
      extent comparable with the effects produced by the same environmental conditions
      on the growth and nutrition of the animals themselves.

PMID- 19869472
TI  - RELAPSE PHENOMENA OF SPIRONEMA RECURRENTIS.
AB  - 1. Squirrels and chipmunks were found to be susceptible to infection with the
      Spironema recurrentis of North China, but no relapses occurred in normal animals.
      2. Splenectomy caused an increase in the intensity of the infection and the
      appearance of one or two relapses. 3. By inoculating splenectomized squirrels
      with a single human strain of spirochetes, six different strains were produced as
      a result of relapses. 4. The strains all retained their specific agglutinating
      characteristics during the period of observation. The oldest strain was observed
      for 132 days and through 38 transfers, the strain last isolated for 22 days and
      through 6 transfers. 5. The sequence of strains in relapses was not always the
      same. Sometimes new strains were produced, at other times there was reversion to
      an older strain. 6. Certain relationships between strains were established. The
      related strains were always those which appeared, or theoretically might have
      appeared, in alternate attacks. In only one case did related strains appear in
      two consecutive attacks. 7. Squirrels whose spleens were not removed had only one
      attack and developed immune substances only against the strain inoculated or
      against closely related strains. It was possible by reinoculation to produce
      infection in such squirrels with as many as four different strains in succession.
      8. The spleen has a protective influence against the development of the relapse
      in the squirrel, but apparently does not control the formation of specific immune
      substances. 9. An explanation of the clinical course of relapsing fever is
      suggested on the basis of the observations recorded. 10. There is, at present, no
      justification for the division of the spirochetes of relapsing fever into
      different species.

PMID- 19869473
TI  - FACTORS INVOLVED IN THE PRODUCTION OF IMMUNITY WITH PNEUMOCOCCUS VACCINE : I.
      ACTIVE AND PASSIVE IMMUNITY DURING THE FIRST SEVEN DAYS AFTER INJECTION OF
      ANTIGEN.
AB  - 1. The antigenic function of a pneumococcus vaccine made from the intact cell was
      compared with that derived fron a watery extract of the cell free from formed
      elements. In each instance, the immunity produced was dependent upon type
      specific protective substance and not upon the elaboration of the common protein
      antibody. 2. The vaccine made from the intact cell resulted in both active and
      passive immunity which began on the 3rd day, increased markedly to the 5th, and
      remained approximately stationery to the 7th day. In the case of the Berkefeld
      filtrate of the shaken bacteria and the filtrate of the broth culture, the
      immunity began on the 4th day, increased to the 5th, and remained approximately
      stationery to the 7th day. The immunity produced by Pneumococcus Type I vaccine
      is greater than that produced by Type II. On the 3rd day, mice vaccinated with
      Type I vaccine resisted 100,000 minimal lethal doses, whereas mice immunized with
      Type II resisted 10,000 minimal lethal doses. On the 5th day, a larger percentage
      of mice survived these doses than on the 3rd day. 3. Certain factors related to
      the preparation and dosage of the vaccine are discussed. 4. As far as the time
      interval and the degree of immunity produced are concerned, these results suggest
      the possibility of employing pneumococcus vaccine in suitable doses in the
      treatment of lobar pneumonia. That an earlier activity of the immunity mechanism
      could actually be initiated in a patient with lobar pneumonia has still to be
      demonstrated.

PMID- 19869474
TI  - THE FATE OF HUMAN AND BOVINE TUBERCLE BACILLI IN VARIOUS ORGANS OF THE RABBIT.
AB  - In this study the attempt has been made to follow the fate of tubercle bacilli in
      the lung, liver, spleen, kidney and bone marrow of rabbits infected intravenously
      with large and small doses of human and bovine tubercle bacilli by determining
      the number of colonies recoverable from similar quantities of tissue on egg media
      at varying intervals during the course of infection. This method offers certain
      possibili-ties for the elucidation of this problem precluded by the modes of
      attack used hitherto. Histological methods, while giving precise data in regard
      to tissue changes produced by the tubercle bacilli, are poor instruments for
      determining the fate of the bacilli in a given organ. Without stressing the
      notorious difficulties in staining the organism at all times, histological
      technique can give no definite answer to the question whether certain stained
      bacilli are living or dead, and it is the number of living bacilli that is of
      importance. Again animal inoculation, while an excellent index of the presence of
      living virulent bacilli, is a very inaccurate index of the number of living
      bacilli in a given specimen of tissue, for it is possible to infect guinea pigs
      with even a very few bacilli.

PMID- 19869475
TI  - AGGLUTINATION BY PRECIPITIN : SECOND PAPER.
AB  - The fact is shown that collodion particles sensitized with various proteins
      adsorb sufficient protein to agglutinate in the presence of precipitin specific
      for the adsorbed protein. The amount of adsorption, judged by agglutination, is
      not dependent on the concentration of the sensitizing protein beyond a certain
      maximum. The agglutination resulting from the addition of immune serum to
      particles sensitized with protein is immunologically specific. Particles exposed
      to a number of antigenic substances in succession are agglutinated by all of the
      appropriate antisera. Particles exposed to immune serum and subsequently washed
      fail to agglutinate in the presence of antigen although some of the protein
      constituents of the immune serum are fixed upon them and its antibody content
      diminishes.

PMID- 19869476
TI  - THE EFFECT OF SOME OF THE CHEMICAL CONSTITUENTS OF TUBERCLE BACILLI ON THE
      PROTOPLASM OF AMOEBA DUBIA.
AB  - 1. Protein fractions derived from tubercle bacilli are toxic to the interior of
      Amoeba dubia but have no action on the plasmalemma. 2. Phosphatide fractions
      dissolve the plasmalemma but have no effect on the internal cytoplasm. 3. The
      fatty acid fraction has a marked solvent action on the plasmalemma when brought
      in contact with the surface of the cell. When injected it may slowly penetrate
      the cytoplasm to dissolve the contiguous plasmalemma. 4. The polysaccharide
      fraction has no effect upon the surface membrane or upon the internal cytoplasm
      of Amoeba dubia.

PMID- 19869477
TI  - THE RELATION OF STREPTOCOCCI TO HERPES VIRUS ENCEPHALITIS.
AB  - Cultures of microorganisms similar to those described by Evans have been obtained
      in media inoculated with suspensions of herpes virus-infected brains prepared by
      grinding. But they have also been isolated from saline suspensions of
      uninoculated meat particles ground in a sterile mortar, and from dextrose broth
      treated in the same way. It is believed that these organisms are contaminants
      introduced during the process of grinding. Since they enter the material in no
      great number, one may suppose them to be suppressed by animals inoculated with
      the ground substance. In artificial media, on the other hand, they find favorable
      conditions for multiplication. In our experience, no growth of microorganisms is
      obtained in routine cultures of virus-infected brains, when fragments, instead of
      ground material, are used-a fact which may be taken to support the explanation
      just given. The tests of the part played by streptococci in experimental virus
      encephalitis failed to disclose that the microorganisms have any etiological
      relationship to the affection. The intracerebral injection of rabbits with the
      cultures procured in the course of the experiments produces a purulent type of
      meningoencephalitis which does not resemble virus encephalitis either in its
      symptom-complex or in its pathology. The same type of meningitis follows the
      injection of streptococci derived from ground meat particles, from "ground"
      broth, from normal brains, and those infected with herpes virus. Some rabbits
      manifested resistance to the streptococci, whereas all that have been inoculated
      intracerebrally with the three strains of herpes virus used in this study have
      proved susceptible thereto. Certain of the rabbits just mentioned which had
      proved resistant to streptococci inoculated into the brain or cornea were
      injected with herpes virus and reacted typically. Comparative tests have revealed
      that the streptococci are more sensitive to the destructive effect of 50 per cent
      glycerol than is herpes virus. From all this, it can be concluded that
      streptococci are not the visible form of herpes virus, nor do they produce in
      rabbits effects like those induced in the brain and cornea by the herpes virus.

PMID- 19869478
TI  - STUDIES ON BLOOD CELL METABOLISM : I. THE EFFECT OF METHYLENE BLUE AND OTHER DYES
      UPON THE OXYGEN CONSUMPTION OF MAMMALIAN AND AVIAN ERYTHROCYTES.
AB  - 1. The respiratory metabolism of non-nucleated mammalian erythrocytes is
      enormously accelerated and approaches the magnitude of the metabolism of the
      nucleated erythrocytes of birds on the addition of methylene blue (and certain
      other dyes), to a final concentration of 0.005-0.0005 per cent. 2. In the
      presence of methylene blue the respiration is accelerated even when M/1000 KCN is
      also present. 3. The accelerated respiration due to methylene blue occurs at room
      temperature but it is most active at 38 degrees . 4. Methylene blue in the above
      concentration accelerates the respiration of avian (goose) erythrocytes to a much
      smaller extent than it does the respiration of the erythrocytes of mammalian
      blood, while the effect upon anemic goose blood seems to be less than it is upon
      cells of normal goose blood. 5. Owing to a rather large initial carbon dioxide
      formation in defibrinated blood on incubation, which may not be related to the
      immediate respiratory process, proper respiratory quotients cannot be obtained in
      whole blood. When the cells are separated from the serum and suspended in Locke's
      solution, respiratory quotients are obtained upon incubation comparable to those
      of other resting mammalian cells, as well as of the actively respiring
      erythrocytes of birds. 6. The hypothesis is advanced that methylene blue acts in
      the role of an oxygen carrier, supplying a substance which has disappeared from
      adult mammalian non-nucleated erythrocytes and restoring their metabolic activity
      to an extent comparable to that of the young immature forms, or to that of the
      actively respiring avian (goose) blood.

PMID- 19869479
TI  - IMMUNOLOGICAL STUDIES IN RELATION TO THE SUPRARENAL GLAND : III. THE EFFECT OF
      INJECTIONS OF EPINEPHRINE ON THE HEMOLYSIN FORMATION IN NORMAL RATS.
AB  - The effect of subcutaneous injections of varying amounts of epinephrine on the
      hemolysin formation of normal adult albino rats was studied. In one group of
      experiments the rats received 0.4 mg. per kilo per day in two injections during 3
      days prior and 4 days subsequent to the injection of sheep cells. Another series
      received the same daily amounts but only during 4 days subsequent to the
      injection of antigen. A third series received the same daily amounts only during
      1 day prior and 2 days subsequent to the injection of sheep cells. In a second
      group of experiments smaller amounts of epinephrine were given during 3 days
      prior and 4 days subsequent to the injection of antigen. The amounts used were
      1/5th, 1/20th, 1/40th, and 1/60th the daily quantity of epinephrine injected in
      the first group of experiments.

PMID- 19869480
TI  - AN EXPERIMENTAL STUDY OF DIATHERMY : VI. CONDUCTION OF HIGH FREQUENCY CURRENTS
      THROUGH THE LIVING CELL.
AB  - 1. A method is described for measuring the relative impedance of living cells to
      diathermy currents. 2. The diathermy current penetrates the living cell, and heat
      production is intracellular as well as extracellular. 3. A small proportion of
      the impedance of living cells to the diathermy current seems not to lead to the
      production of heat. 4. Evidence is given that the addition of saponin produces an
      appreciable increase in the conductivity of an electrolyte. Its use is therefore
      contraindicated when electrical measurements are being made on biological
      material. 5. The currents used in diathermy behave as do high frequency currents
      of the pure sine wave form in respect to their passage through biological
      material.

PMID- 19869481
TI  - STUDIES ON BACILLUS TYPHOSUS TOXIC SUBSTANCES : I. PHENOMENON OF LOCAL SKIN
      REACTIVITY TO B. TYPHOSUS CULTURE FILTRATE.
AB  - A phenomenon of local skin reactivity to B. typhosus culture filtrates is
      described in this report. The reactivity was induced by skin injections of the
      filtrate followed 24 hours later by an intravenous injection of the same
      filtrate. The local response consisted of severe hemorrhagic necrosis and was
      fully developed 4 to 5 hours after the second injection. About 78 to 79 per cent
      of the rabbits employed were susceptible to this phenomenon. Different areas of
      the skin of the abdomen, when similarly treated, responded with equal severity to
      the intravenous injection. There were variations in the size of different areas
      in the same animals. The intensity and size of the local hemorrhagic reactions
      were not related to the intensity of the erythema produced by the preparatory
      skin injections. Following intravenous injection very severe hemorrhagic
      reactions were obtained, in those areas which reacted negatively in this respect
      to the preparatory skin injections. Evidently, the local trauma produced by the
      preparatory skin injections was not responsible for the localization of the toxic
      factors introduced by the intravenous route. It was necessary to allow a short
      interval of time between the skin preparatory injections and the intravenous
      injection, for the reproduction of the phenomenon. An incubation period of 2
      hours was insufficient. An interval of 24 hours was invariably sufficient. The
      ability to react disappeared in 48 hours after the preliminary skin injections.
      Repeated direct injections of the filtrate into the same areas of the skin, with
      an interval of 24 hours between the injections, did not result in reactions
      similar to the above described hemorrhagic necrosis. The second skin injection
      was followed by reddening, some swelling and a local accumulation of
      polymorphonuclear neutrophil leucocytes which showed no signs of necrobiosis.
      There was no rupture of blood vessels. Skin injections followed after a suitable
      interval by intravenous injection, were necessary for the reproduction of the
      severe local hemorrhagic response. Skin reactivity to B. typhosus culture
      filtrate injected intravenously was not induced by turpentine in various
      dilutions, sterile tryptic digest broth, culture filtrates of 4 strains of
      streptococci or by the Streptococcus erysipelatis toxin. It was possible to
      titrate the skin preparatory factors. Dilutions of the filtrate up to 1:64 were
      able to induce the local skin reactivity. But, whereas dilutions up to 1:4
      invariably prepared the skin so that very severe hemorrhagic reactions followed
      the second injection in susceptible animals, dilutions from 1:8 to 1:64 were
      uncertain and their preparatory effect varied in different animals. The skin
      preparatory factors showed considerable heat resistance. The heat resistance
      varied with the strains employed. One strain produced factors totally resistant
      to heating in the autoclave for 1 hour. However, there was definite and
      unquestionable inactivation of these factors as derived from other strains when
      the filtrate was diluted 1:2 and heated in the autoclave. Various hydrogen ion
      concentrations in the range from 9.0 to 4.0 had no effect upon the skin
      preparatory factors. Heat resistance was not modified by the various pH within
      this range. The mechanism of the phenomenon described has not been fully studied
      as yet. An experimental comparison of it with the manifestations of bacterial
      allergy of the skin is necessary. There are certain features, however, which
      considered together, distinguish this phenomenon from the known phenomena of
      bacterial hypersusceptibility. These features are: local reactivity; the short
      incubation period necessary to induce the local reactivity; the short duration of
      the state of reactivity; the ability to induce local reactivity by a single skin
      injection; the severity of the reaction; and the necessity to make the second
      injection of the toxic agent by the intravenous route. Studies on the relation of
      specific antisera to the phenomenon described are under way.

PMID- 19869482
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : IX. EVIDENCE OF HYDROLYSIS OF
      BACTERIAL PROTEIN DURING LYSIS.
AB  - 1. During the process of lysis by bacteriophage, there is an appreciable increase
      in the amount of free amino acid present in the culture. 2. The increase of free
      amino acid is due to hydrolysis of bacterial protein.

PMID- 19869483
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : X. TOXIN PRODUCTION BY NORMAL AND BY
      PHAGE-RESISTANT SHIGA DYSENTERY BACILLI.
AB  - 1. The production of exotoxin and of endotoxin by normal Shiga dysentery bacilli
      and by strains resistant to Laudman phage was found to be the same. 2. The
      presence of phage did not alter toxin production by the resistant organism.

PMID- 19869484
TI  - THE FUNDAMENTAL PROPERTIES OF THE FIBROBLAST AND THE MACROPHAGE : IV. THE
      MALIGNANT FIBROBLAST OF JENSEN SARCOMA.
AB  - 1. A pure strain of fibroblasts has been isolated from the Jensen rat sarcoma.
      The cells give rise to tumors on transplantation into animals and during several
      months of life in vitro have maintained their malignancy unchanged. 2. The
      malignant cells are generally coarser and more refringent than normal cells. They
      possess the cytological characteristics of fibroblasts without showing any
      morphological abnormality. They can be considered as healthy cells. The texture
      of their colonies is looser than that of normal fibroblasts and Sarcoma No. 10
      fibroblasts. Their residual activity does not differ markedly from the normal.
      They proliferate unlimitedly in a nutrient medium. 3. They liquefy the fibrin of
      rat plasma and turn phenol red golden yellow. They do not liquefy the fibrin of
      chicken plasma. 4. They multiply in chick embryo juice, calf liver digest, and
      also in rat serum. Their growth activity is increased by the presence of bone
      marrow. 5. The unlimited growth of Jensen sarcoma within the body may possibly be
      attributed to the ability of the fibroblasts to maintain themselves upon the
      substances present in rat serum. This property itself probably depends upon the
      increased enzyme activity of the cells.

PMID- 19869485
TI  - RECIPROCAL AGGLUTINATION AND ABSORPTION OF AGGLUTININ TESTS WITH FIFTY-FOUR
      STRAINS OF HEMOLYTIC STREPTOCOCCI ASSOCIATED WITH AN EPIDEMIC OF PUERPERAL FEVER.
AB  - 1. A study has been made by means of agglutination and absorption of agglutinin
      tests, of the antigenic relationships of 54 strains of hemolytic streptococci
      associated with an epidemic of puerperal fever in a large city obstetric
      hospital. 2. These organisms were cultured from the blood, vaginae, peritoneal
      cavities and metastatic foci of patients, from the noses and throats of patients
      and staff members and from the peritoneum and axillary abscess of two of the
      nurses. 3. In preliminary agglutination tests twenty-one out of thirty-one
      cultures from the patients and nine out of twenty-three cultures from the
      hospital personnel, fell into a single agglutinative group. 4. By reciprocal
      agglutination and absorption of agglutinin tests, six of these strains were
      demonstrated to be antigenically identical. Two of these came from patients'
      blood cultures, three from patients' vaginal cultures and one from the nasal
      culture of one of the nurses. This nurse was, however, not the original carrier
      for she did not join the hospital staff until after the epidemic began. 5. By
      agglutination and complete absorption of agglutinin, sixteen more strains showed
      their antigenic similarity to, if not identity with, these other six strains.
      Four of these sixteen came from metastatic foci and two from the vaginae of four
      of the five patients which had yielded from another source, the identical strains
      mentioned in 4. Nine came from eight other patients and one from the axillary
      abscess of a nurse. No reciprocal tests were possible with these sixteen strains
      because sera had not been prepared against them. 6. Five other strains which
      completely absorbed agglutinin had evidently lost their ability to agglutinate.
      Two of these strains were from the blood cultures and two from the vaginal
      cultures of two fatal cases. One was from the peritoneal cavity of a nurse. 7.
      Two of these five strains when injected into rabbits in the usual way for the
      purpose of producing agglutinating antiserum, stimulated the production of sera
      which agglutinated completely the six antigenically identical strains but failed
      to agglutinate the homologous strains used to produce the respective sera. 8.
      These two strains therefore retained the antigenic properties first of
      stimulating the agglutinating antibody in normal animals and second of uniting
      with the agglutinating antibody in the serum but lost the ability to bring about
      the second phase of agglutination-namely flocculation. 9. We have demonstrated,
      therefore, a more or less permanent splitting of the phenomenon of agglutination.

PMID- 19869486
TI  - SEROLOGICAL DIFFERENTIATION OF STERIC ISOMERS.
AB  - The tests presented in Tables I, II, and III show that only in the higher
      concentration cross reactions do take place, and that there is definite
      specificity of the two sorts of immune sera for the homologous antigens. Thus it
      is easy to differentiate the l- and d-antigens in dilutions 1:100 and upwards.
      The occurrence of cross reactions can readily be ascribed to the fact that the l-
      and d-acids present in the two antigens are identical in every respect but the
      position of the groups connected with the asymetric carbon atom. The i-antigen
      reacts with both sorts of immune sera as could be expected since it must consist
      of a mixture of equal parts of l- and d-antigen. The reactions of the i-antigen
      appear to be only slightly weaker than those of the homologous ones owing to the
      fact that the intensity of the reactions diminishes but slowly with increasing
      dilution of the antigens. It is also to be considered that small differences
      cannot be judged very accurately. Tests with two l- and four d-immune sera not
      recorded in the tables confirmed the results already discussed. Considering that
      ferments are known to be adapted ordinarily to one type of steric isomers it may
      be worth noting that antibodies were formed by the same species of animals for
      optical antipodes. From the results summarized in Tables IV,a and IV,b one sees
      that the l- and d-immune sera also differentiate clearly between the l- and d
      acids when they are not diazotized and not combined with protein. The l-acid
      inhibits much more the precipitation of the l-antigen by the homologous immune
      serum than the d-acid and the converse effect occurs if the inhibiting action is
      tested on the precipitation of d-antigen by d-immune serum. The inactive phenyl
      (para-aminobenzoylamino) acetic acid behaved in such tests as a mixture of l- and
      d-acids, i.e., it acted markedly in both cases, more than the heterologous and
      less than the homologous acid. The experiments reported bring a definite proof
      for the view that the steric configuration of antigenic groups is one of the
      factors determining serological specificity. In the particular case under
      consideration the mere difference in the position of H and COOH as indicated in
      the following formulas sufficed to alter the reactivity. See PDF for Equation.
      The fact that steric isomers are acted upon selectively by immune sera may be
      supposed to play a significant part in the serological specificity of
      carbohydrates such as those discovered in bacterial antigens.

PMID- 19869487
TI  - THE INFLUENCE OF CHOLESTEROL ON EXPERIMENTAL TUBERCULOSIS.
AB  - 1. Cholesterol, administered intraperitoneally, in these experiments definitely
      prolonged the lives of tuberculous guinea pigs when the infection was of an acute
      type produced by inoculation with a small dose of very virulent human type
      organisms. 2. Intraperitoneally administered cholesterol did not definitely
      prolong the lives of tuberculous guinea pigs when the infection was of the
      chronic type produced by the injection of a small dose of human type tubercle
      bacilli of relatively low virulence, or when the infection was more acute owing
      to the injection of a large dose of organisms of low virulence. It had no
      beneficial effect on an acute type of infection produced by the bovine type
      organism. 3. Cholesteryl chloride, cholesteryl toluide, cholesteryl anilide,
      sodium cholesterol sulfate, and quinine cholesterylate did not significantly
      prolong the lives of tuberculous guinea pigs. 4. Sodium cholesterylate, in
      optimal dosage, definitely prolonged the lives of tuberculous guinea pigs. 5.
      There was a significant shortening in the duration of life of tuberculous guinea
      pigs subjected to the trauma of intraperitoneal injection and repeated handling
      as compared with tuberculous guinea pigs that were not handled or traumatized by
      intraperitoneal injections.

PMID- 19869488
TI  - CHEMICAL CHANGES IN THE BLOOD OF THE DOG IN EXPERIMENTAL PERITONITIS.
AB  - 1. A study of the blood chlorides, urea and non-protein nitrogen and the carbon
      dioxide-combining power in experimental general peritonitis is here reported. 2.
      The similarity between the chemical changes in high intestinal obstruction and
      general peritonitis is noted. These chemical changes suggest that the cause of
      death may be, at least in part, the same in the two diseases.

PMID- 19869489
TI  - THE EFFECT OF OXIDATION OF FILTRATES OF A CHICKEN SARCOMA (CHICKEN TUMOR I-ROUS).
AB  - 1. The rapid autoinactivation at 37 degrees of candle filtrates of the Rous Foul
      Sarcoma I is due in large part to oxidation. 2. Such oxidation may be prevented
      by a dilution of 1-2000 cysteine hydrochloride brought to pH 7.4 with NaOH. 3.
      The variability of infectiousness of candle filtrates is due in part at least to
      oxidative changes which take place during their preparation; and more active
      extracts may be obtained by preventing these by means of cysteine. 4. For
      elaborate experiments it is possible to preserve filtrates in the ice box with
      cysteine and vaseline until test inoculations have established their infectivity.

PMID- 19869490
TI  - THE RELATION OF THE CAPSULAR SUBSTANCE OF B. COLI TO ANTIBODY PRODUCTION.
AB  - The relation between a strain of B. coli and its mutant with reference to the
      production of agglutinins and protective antibodies may be expressed by the
      statement that the original strain when injected into cows develops antibodies
      both towards itself and the mutant whereas the mutant produces them only towards
      itself. The results point to the capsular substance as the material carrying
      virulence or, expressed somewhat differently, the factor which protects the
      microorganism in the host.

PMID- 19869491
TI  - RECIPROCAL EFFECTS OF CONCOMITANT INFECTIONS : III. THE INFLUENCE OF VACCINIA AND
      OF VACCINAL IMMUNITY ON THE REACTION TO INFECTION WITH EXPERIMENTAL SYPHILIS
      (INTRACUTANEOUS INOCULATION).
AB  - An experiment is reported in which was studied the effects of a concomitant
      vaccinal infection and of vaccinal immunity upon the reaction to syphilis in
      rabbits induced by intracutaneous inoculation. The results obtained showed that
      the reaction was modified by both conditions. A vaccinal infection initiated at
      the time of syphilitic inoculation was associated with a defensive reaction of
      lessened efficiency, the ensuing syphilis being more severe than in control
      animals. A state of vaccinal immunity present at the time of syphilitic
      inoculation was associated with a reaction of heightened efficiency, the ensuing
      syphilis being very mild. These results are in harmony with those obtained in
      other experiments in which the intratesticular route of syphilitic inoculation
      was employed.

PMID- 19869492
TI  - THE ACTION OF THE LEVADITI STRAIN OF HERPES VIRUS, AND OF VACCINE VIRUS IN THE
      GUINEA PIG : SINGLE AND COMBINED EFFECTS.
AB  - A number of methods have been employed in attempts to induce encephalitis in
      guinea pigs with the Levaditi C strain of herpes virus. Some of these consisted
      of different modes of inoculation of the virus itself and others of different
      ways of combining it with vesicular stomatitis and neurovaccine viruses so as to
      obtain the concomitant effects of both. In still another test the Levaditi virus
      was combined with the neurovaccine in a manner calculated to bring about the
      maximum action of each at the same time. By all these methods, the Levaditi virus
      failed to evoke the characteristic encephalitis which this specimen is capable of
      inducing uniformly in rabbits. On the other hand, when the Levaditi herpes virus
      is inoculated into the brain of guinea pigs in conjunction with suitably timed
      corneal injections, it acquires active encephalitogenic properties. The results
      just noted suggest several considerations: 1. The possibility of increasing the
      virulence of a filtrable virus by animal passage in a special manner. It is not
      likely that the increase as observed was due to dosage, for after the virus
      acquired its encephalitogenic property for guinea pigs, the usual amounts of
      virus suspensions sufficed to induce, in a uniform way, typical encephalitis. 2.
      The opinion previously expressed by Flexner that the guinea pig serves merely to
      separate weak from strong strains of herpes virus is supported: for only
      according to the particular method described, could the encephalitogenic power of
      the Levaditi virus be developed and the weak be converted into a strong herpes
      strain. With the acquisition of this power, the Levaditi virus acted in precisely
      the same manner as strong herpes strains both in the guinea pig and the rabbit.
      Moreover, it was shown in guinea pigs that cross-immunity occurs between weak and
      strong strains. 3. The two samples of neurovaccine virus employed were incapable
      of inducing encephalitis in guinea pigs after intracutaneous, intratesticular,
      corneal, or intracerebral inoculation, although they were actively
      encephalitogenic in rabbits. In spite of the fact that the vaccine virus and
      herpes virus are different, as shown by the histopathology and absence of cross
      immunity, they behave in the same way when injected into the brain of the guinea
      pig. The failure of the concomitant action of both viruses to induce encephalitis
      in the guinea pig suggests that the association of two viruses, under the
      experimental conditions outlined, is incapable of inducing encephalitis, if
      either, by itself, is non-encephalitogenic. 4. The serum from normal guinea pigs
      may neutralize a weak (Levaditi C) but not a strong (H.F.) strain of herpes
      virus; but the neutralizing action of the serum on Levaditi C virus is not
      uniform. 5. The Levaditi strain of virus can increase in quantity in the brain of
      the guinea pig to a degree which permits detection and yet fails to evoke any
      distinctive clinical picture or definite histopathological changes. 6. Repeated
      intraperitoneal injections of Levaditi virus in guinea pigs elicit no signs of
      infection, yet they induce a solid immunity to strong strains of herpes virus.

PMID- 19869493
TI  - STUDIES ON INDIFFERENT STREPTOCOCCI : I. SEPARATION OF A SEROLOGICAL GROUP-TYPE
      I.
AB  - Serological study of a large number of strains of indifferent streptococci has
      revealed the existence of a large homogeneous group to which the designation Type
      I has been applied. It is recognized that members of Type I are not necessarily
      identical, and that further division into subtypes may be feasible. All strains
      of Type I ferment inulin and salicin. The remaining strains are referred to as
      belonging to Group X. They are distinguished only by their failure to react
      strongly with Type I serum. While at present this group must be regarded as quite
      heterogeneous, further work may reveal the presence of other as yet undefined
      types now included within its limits. The organisms of this group vary in their
      fermentative reactions with both inulin and salicin.

PMID- 19869494
TI  - STUDIES ON INDIFFERENT STREPTOCOCCI : II. OBSERVATIONS ON THE DISTRIBUTION OF
      INDIFFERENT STREPTOCOCCI IN THE THROATS OF RHEUMATIC AND NON-RHEUMATIC
      INDIVIDUALS.
AB  - Indifferent streptococci occur in comparatively the same abundance in the throats
      of patients suffering from rheumatic fever or early in convalescence from the
      disease as they do in those who have recovered from the disease, or in those of
      patients suffering from other diseases. There is a slightly increased incidence
      of these microorganisms in the throats of hospital patients as compared with
      those of normal individuals. Type I occurs with comparatively equal frequency and
      abundance in the throats of all four classes of individuals studied.

PMID- 19869495
TI  - FURTHER EXPERIMENTS WITH THE INTRADERMAL PNEUMOCOCCUS INFECTION IN RABBITS.
AB  - 1. The continuation of our experiments with intradermal Type I pneumococcus
      infection in rabbits has furnished further evidence of the marked analogies
      between this condition and that of human lobar pneumonia. 2. It has been found
      that the amount of antiserum necessary for successful therapy increases as the
      disease progresses, and that this progression has a definite mathematical
      character. Such a condition, it seems, can only be caused by a progressive
      accumulation of some toxic or antagonistic substance, the exact nature of which
      is not known. 3. Various lots of antipneumococcus sera have been tested for their
      therapeutic properties. The results from seven such sera show that this
      therapeutic value does not parallel the mouse-protective value. It is suggested
      that the rabbit technic may prove useful for the routine comparison and
      standardization of antipneumococcus sera since it represents a simple method for
      determining that property for which the serum is to be utilized. 4. The effect of
      non-specific therapy in this condition has been determined to be a transient
      disappearance from the blood stream of circulating organisms. This result was
      obtained with such heterologous materials as normal horse serum and typhoid
      vaccine but not with the homologous normal rabbit serum. 5. Rabbits recovering
      from the intradermal disease without treatment or with such inadequate treatment
      that the disease runs its normal course, were shown to have a definite though not
      permanent immunity. Cases in which the disease had been arrested at 24 hours by
      effective therapy with heterologous immune serum showed no immunity after the
      early disappearance of the passively administered elements. Cases which were
      brought to early recovery with immune homologous serum did show a definite
      immunity comparable to that which was developed in other animals as the result of
      an untreated course of the disease. 6. The immunity conferred by single and
      multiple vaccination is reported. The possibility of the application of such
      methods in the pneumonias of man is discussed and a method for such an
      application is suggested.

PMID- 19869496
TI  - THE ROLE OF STREPTOCOCCI IN EXPERIMENTAL POLIOMYELITIS OF THE MONKEY.
AB  - It is the opinion of Bull, that the streptococci recovered from poliomyelitic
      tissues, while having no etiological or pathological relationship to the virus of
      poliomyelitis, occur as secondary invaders in the disease. Smillie and Amoss
      indicated that the bacteria may be agonal invaders. The results of the
      experiments reported in this paper point to another source of the streptococci.
      They occur as contaminants which are introduced into the cultures during the
      process of grinding tissues. The source of the streptococcus may therefore be the
      air of the place in which the cultures are made. We have come to this conclusion
      because first, the tissues of which cultures yielded streptococci were derived
      from a number of monkeys with experimental poliomyelitis still in a vigorous
      state. Secondly, when the tissues were ground bacteria were noted much more
      frequently in their cultures than in those in which fragments of the same brains
      were used. Thirdly, microorganisms occurred more often in cultures made in the
      routine laboratory than in a special room where asepsis was carried to the
      extreme of a major surgical operation on man. Fourthly, streptococci were
      obtained from the air of the places where cultures were made. Finally, there is
      no correlation between the cultures of two portions of the same brain. The
      streptococci occurred in some cultures in pure growth and in others admixed with
      other ordinary species of bacteria. The latter were often found, in turn, in pure
      culture and what applies to streptococci, as mentioned in the preceding
      paragraph, applies equally to the staphylococci, diphtheroids, spore-bearing
      rods, and other miscellaneous, familiar microorganisms. We could not determine
      that there exists any etiological relation of the streptococci to poliomyelitis.
      The fermentation reactions of the microorganisms obtained from the air, from non
      poliomyelitic and poliomyelitic monkey brains indicate that bacteria from any of
      these sources are markedly different. So also with the serological reactions of
      agglutination and precipitation. Furthermore no agglutination was observed when
      the serum of monkeys convalescent from experimental poliomyelitis was mixed with
      any of the streptococci recovered or those received directly or indirectly from
      Rosenow. Moreover, the intracerebral injection with cultures, irrespective of
      their source, induced in rabbits a purulent type of meningoencephalitis, often
      associated with streptococcic septicemia. This result is at marked variance with
      any known effects of the true filtrable virus of poliomyelitis in man and in the
      monkey.

PMID- 19869497
TI  - VIRUS NEUTRALIZATION EXPERIMENTS WITH ROSENOW'S AND PETTIT'S ANTIPOLIOMYELITIC
      SERA.
AB  - 1. The Rosenow antistreptococcic poliomyelitis serum concentrated or
      unconcentrated does not neutralize the virus of poliomyelitis as tested in
      monkeys. 2. The Pettit antipoliomyelitis horse serum neutralizes the virus only
      occasionally. 3. "Immune" sheep sera prepared according to the method of Pettit
      have not neutralized virus even when the normal sera of the same animal have
      given neutralization. 4. The reason for such chance neutralizations is obscure
      and should not be confused with the constant virus-neutralizing action of both
      human and monkey convalescent sera. 5. Experimental evidence affords no basis for
      the use of either the Rosenow or the Pettit serum in the therapy of
      poliomyelitis.

PMID- 19869498
TI  - STUDIES UPON THE EFFECT OF LIGHT ON BLOOD AND TISSUE CELLS : I. THE ACTION OF
      LIGHT ON WHITE BLOOD CELLS IN VITRO.
AB  - 1. An extreme and rapid degeneration which occurred in tissue cultures of
      leucocytes from the blood of cats, guinea pigs, and rabbits, is described in
      detail. 2. This degeneration was found to appear in the culture when the cells
      were planted in any of the culture media tried, some of which were autogenous
      heparin plasma, autogenous plasma, autogenous serum, Tyrode solution, and
      mixtures of these with embryo juice. 3. The specific cellular changes which
      occurred are described for the different leucocytes. In general, there was first
      a latent period during which no change could be observed in the cell. Following
      this there was a period of stimulation during which the motion of the cell was
      greatly accelerated. This second stage has been observed in all cells except the
      lymphocyte, in which it may possibly occur to a slight degree. Finally there was
      the terminal stage, the stage of degeneration, in which the cell rounded up, lost
      its motility, and either became badly swollen or else underwent a more or less
      complete coagulation. 4. The factor causing this degeneration was found to be
      exposure of the culture to light, as, for example, during microscopic
      examination. 5. By a reduction of the infrared part of the spectrum, it was
      indicated that the effect was not due to a heat coagulation of the cells. 6. This
      degeneration was also found to occur in the complete absence of ultra-violet wave
      lengths. 7. Further, it was shown that this degeneration was caused by light
      which lay within each of the three wave-length zones (1) 430micromicro to
      550micromicro; infra-red; (2) 475micromicro to 630micromicro; 690micromicro to
      infra-red; (3) 600micromicro to infra-red. 8. No indication was given as to
      whether all regions of these zones were active in causing the degeneration, or
      whether the active rays are limited to certain wave-length bands lying within
      these zones. 9. This degeneration of the leucocytes under the action of light was
      also found to occur upon irradiation of hanging drops of whole blood. This is
      interpreted as showing conclusively that the degeneration was not dependent upon
      the additional factors of centrifugation, continued lowering of temperature, or
      the presence of abnormal saline solution. 10. It was noted, however, that the
      leucocytes in hanging drop cultures required a markedly longer time for their
      degeneration under the action of light than did the leucocytes in cultures
      prepared from the buffy coat and inoculated in serum. This is considered as
      possibly due, either to injury to the cell during centrifugation and subsequent
      handling, or to some action of the red blood cells present in large amounts in
      the hanging drops of whole blood. 11. In these hanging drop cultures of whole
      blood degeneration of the leucocytes was also found to occur when the light
      reaching the culture was first freed from the larger part of its infra-red and
      from all of its ultra-violet. 12. It was also shown that the same degeneration
      was produced by wave-lengths of light lying within each of the three wave-length
      zones defined in Section 6 of this summary.

PMID- 19869499
TI  - THE TRANSFER OF RAT ANEMIA TO NORMAL ANIMALS.
AB  - Fifty-eight white and hooded rats have been splenectomized and all of them have
      shown a more or less severe anemia and an infection of the red blood cells with
      Bartonella muris. Another strain of white rats obtained from Littlestown showed
      no anemia and no bartonellas in the blood after splenectomy, until exposed to
      infected rats. Others of these Littlestown rats, kept in the laboratory for some
      time before operation and exposed to infected rats, came down with bartonella
      anemia within 6 days after splenectomy. Whole blood or the washed red blood
      corpuscles from splenectomized rats which show bartonellas and anemia will
      produce a similar condition in young rats when injected intraperitoneally. Adult
      rats of strains which harbor the virus (as demonstrated by splenectomy) cannot be
      infected by injection. Intravenous inoculation of young normal rabbits with blood
      from an infected rat will sometimes produce a similar infection and anemia in the
      rabbit, and the virus can then be transferred back to young rats. The virus of
      rat anemia may be transferred from young normal rat to young normal rat with the
      appearance of Bartonella muris and the production of anemia. In the early
      transfers the disease may be fatal, but it usually becomes milder in successive
      passages. Although we have not yet been able to cultivate Bartonella muris and
      prove its etiological relationship to rat anemia by inoculation of cultures, we
      have added to the evidence that Bartonella muris is the cause of the anemia.
      Washed red blood corpuscles, containing bartonellas, will produce the anemia in
      the usual way while plasma from the same cells will either fail to produce it
      altogether or only after a prolonged incubation period. Blood heated to 57
      degrees C. for (1/2) hour fails to produce anemia or the appearance of
      bartonellas in the blood of inoculated animals. From these observations the
      following conclusions may be drawn: 1. All rats which harbor Bartonella muris
      ratti come down with a more or less severe anemia after splenectomy. 2. Young
      rats which have not yet developed an immunity undergo the typical anemia after
      intraperitoneal injection of blood from a splenectomized animal in the early
      stages of the anemia. 3. Young rabbits may show bartonellas and develop anemia
      following intravenous inoculation of infected blood. 4. The virus of rat anemia
      and Bartonella muris ratti may be transferred from normal animal to normal animal
      for successive generations. Such strains have now been transferred for five, nine
      and thirty generations. 5. The resistance of rats to bartonella anemia is almost
      wholly dependent on the spleen. Other organs do not take over this function of
      protection as shown by the relapse of splenectomized rats many months after
      recovery. Young rats which have recovered from an attack of anemia are not
      protected by this previous infection from the invasion of the virus following
      splenectomy. Adult splenic tissue mixed with infected blood before injection does
      not inhibit or neutralize the virus. 6. The virus of rat anemia is highly
      contagious and rats exposed to infection acquire it in some unknown way. 7.
      Bartonella muris ratti represents the virus of rat anemia or at least cannot be
      separated from the virus because: (a) The anemia in splenectomized and injected
      animals is always preceded by the appearance of bartonellas and the grade of
      anemia is proportional to the degree of infection with bartonellas. (b) Washed
      corpuscles containing bartonellas always produce anemia. Plasma either fails to
      do so, or produces a mild anemia after a long incubation period with a few
      bartonellas in the blood. (c) The thermal death point of virus and bartonella is
      the same.

PMID- 19869500
TI  - THE CONVERSION OF HEMOLYTIC STREPTOCOCCI TO NON-HEMOLYTIC FORMS.
AB  - From one strain of hemolytic streptococcus three forms were isolated, which
      produced three different degrees of hemolysis on the surface of blood agar in the
      presence of oxygen. The original form was moderately hemolytic; the glossy
      variant was more hemolytic than the original form; and the third form, obtained
      by passing the original culture through mice, was non-hemolytic. Under anaerobic
      conditions all three forms were hemolytic. The non-hemolytic passage culture, in
      the presence of an ample supply of oxygen, not only destroyed its own hemolysin,
      which only appeared under anaerobic conditions, but was also able to destroy the
      hemolysin of other cultures of hemolytic streptococci. It is possible that these
      observations may throw some light on experiments reported by a number of workers
      showing that Streptococcus haemolyticus can be transmuted to Streptococcus
      viridans by animal passage.

PMID- 19869501
TI  - A STUDY OF THE MECHANISM OF RECOVERY FROM LOBAR PNEUMONIA.
AB  - Employing a method devised for the investigation of natural immunity and
      experimental pneumococcus infection, a study has been made of the serum immune
      changes occurring during the course of lobar pneumonia due to Pneumococcus Types
      I and II and Group IV, in man. It was found that at the time of crisis or lysis
      the blood serum acquired constantly the property of promoting pneumococcus
      killing to a relatively marked degree. Other evidences of antipneumococcus
      reaction-mouse protection, opsonins, and agglutinins-were also demonstrable in
      the blood at this time. These immune changes appeared in the majority of cases at
      the beginning of recovery and failed to occur when the disease terminated
      fatally. The fact that these observations in human cases are practically
      identical with previous findings in the experimental disease in cats, enhances
      considerably the significance of the development of serum immune bodies at the
      time of crisis since in the experimental animal it was possible to show that the
      acquisition of passive immunity was associated with greatly increased
      antipneumococcus resistance.

PMID- 19869502
TI  - NITROGEN METABOLISM OF NORMAL AND SARCOMATOUS FIBROBLASTS IN PURE CULTURES.
AB  - 1. Both normal and sarcomatous fibroblasts of the rat utilize many different
      fragments of the protein molecule for their growth in vitro. Alpha and beta
      proteoses have approximately equal growth-promoting power. 2. A mixture of
      peptones, peptides, and amino acids, containing a negligible quantity of
      proteose, produces a temporary proliferation of normal fibroblasts, and an
      unlimited multiplication of sarcomatous fibroblasts, provided these substances
      are derived from liver which contains products of unknown nature that complete
      the nutritive effect of the protein degradation products. 3. Amino acids
      contribute to the nutrition of the cells, but are unable without the addition of
      peptides or polypeptides to support their life. 4. The proteolytic products are
      more toxic to normal than to sarcomatous fibroblasts. The hypothesis is suggested
      that the greater acidity produced by the large glycolysis of the sarcomatous
      cells may account for this difference through altering the speed of action of
      protein synthetizing enzymes.

PMID- 19869503
TI  - BIOMETRY OF CALCIUM, INORGANIC PHOSPHORUS, CHOLESTEROL, AND LIPOID PHOSPHORUS IN
      THE BLOOD OF RABBITS : I. NORMAL ANIMALS FROM RECENTLY ACQUIRED STOCK.
AB  - Determinations of calcium, inorganic phosphorus, cholesterol and lipoid
      phosphorus were made on a series of animals recently received from the dealer for
      the purpose of determining the trends of these 4 blood constituents throughout
      the year with the degree of their respective variations and mathematical
      correlation. It was found that for the 80 animals examined, calcium varied from
      14.5 +/-0.10 to 18.5 +/-0.39 mg. and inorganic phosphorus 4.960 +/-0.20 to 6.820
      +/-0.20 mg. per 100 cc. of blood serum. Cholesterol varied from 51.1 +/-1.18 to
      73.3 +/-1.34 mg. and lecithin from 94.8 +/-1.397 to 168.3 +/-10.18 mg. per 100
      cc. of whole blood. Of the 6 possible combinations in calculating the coefficient
      of correlation for the trend throughout the experiment, 3 stand out as of
      mathematical significance, namely the following. Between inorganic phosphorus and
      lecithin the coefficient of correlation was found to be -0.794 +/-0.088; between
      calcium and cholesterol -0.887 +/-0.051 and between cholesterol and lecithin
      +0.560 +/-0.164.

PMID- 19869504
TI  - INFLUENCE OF LIGHT ENVIRONMENT ON THE ORGANIC CONSTITUTION OF NORMAL RABBITS WITH
      ESPECIAL REFERENCE TO THE ACTION OF NEON LIGHT.
AB  - The influence of light environment on the organic constitution of normal rabbits
      was studied by comparing the weights of organs of animals that had been living
      under cerrtain conditions for long periods of time. It was found that the light
      environment produced an effect on the physical constitution of the rabbits which
      was comparable to the effects produced on the functional activity of the same
      animals.

PMID- 19869505
TI  - CHEMICAL FINDINGS IN THE BLOOD OF THE DOG AFTER TEMPORARY OBSTRUCTION OF THE
      PYLORUS.
AB  - The toxemia characteristic of upper gastrointestinal tract obstruction may be
      produced by temporary obstruction of the pylorus. This procedure affords an
      opportunity for studying the toxemia in the absence of mechanical factors,
      operative risk, and infection. Animals which spontaneously recover from the
      toxemia may show a return of the blood chloride to normal when only distilled
      water is given. In such instances there must be a redistribution of the body
      store of chlorides. The administration of sodium chloride by mouth to animals
      which show a toxemia without evidence of spontaneous recovery causes a rapid
      return of the blood to normal. There is a marked diuresis with high nitrogen
      excretion during the toxemia. This is evidently due to the increased protein
      destruction. The return of the blood chlorides to normal causes a cessation of
      the increased protein destruction.

PMID- 19869506
TI  - VIRUS III ENCEPHALITIS.
AB  - Virus III, an active, filterable agent indigenous to rabbits, under experimental
      conditions produces, in addition to lesions in the cornea, skin, and testicles,
      an encephalitis which is at times quite similar to that induced by herpetic
      virus. Virus III and herpetic virus, however, are not immunologically related.

PMID- 19869507
TI  - SURFACE TENSION OF SERA AS AFFECTED BY THE PRECIPITIN REACTION.
AB  - An attempt to find evidence, through the study of surface tension, using the du
      Nouy tensiometer, of a denaturing effect of the precipitin reaction upon either
      the antigen or the immune serum yielded entirely negative results.

PMID- 19869508
TI  - ETIOLOGY OF OROYA FEVER : XIII. CHEMOTHERAPY IN EXPERIMENTAL BARTONELLA
      BACILLIFORMIS INFECTION.
AB  - The therapeutic effect of several antiparasitic chemicals on experimental verruga
      peruana is described. The drugs were administered by intravenous injection
      according as the nodules (1) were already developed to an approximate maximum, or
      (2) were still in the active period of growth. The effect of the drugs was
      different under the two circumstances of their administration. When they were
      given after the maturity of the nodules they hastened the regressive process, but
      when given during active growth of the lesions no action whatever was detected.
      Bartonella bacilliformis in culture is acted upon injuriously by a number of the
      chemicals employed in the therapeutic tests, the most active being formalin and
      neutroflavine.

PMID- 19869509
TI  - THE EFFECT OF SODIUM CHLORIDE ON THE CHEMICAL CHANGES IN THE BLOOD OF THE DOG
      AFTER OBSTRUCTION OF THE CARDIAC END OF THE STOMACH.
AB  - A study is reported of the effect of different methods of treatment on the
      toxemia of cardiac obstruction. The average duration of life of untreated dogs is
      3 days. Three dogs treated with 1 per cent salt solution subcutaneously lived 32,
      36, and 45 days respectively without developing a toxemia. 2 per cent glucose
      similarly given, does not alter the course of the toxemia. Concentrated salt
      solution in small quantities given directly into the jejunum prevents the marked
      rise in non-protein nitrogen but does not materially prolong life. Release of the
      obstruction does not change the course of the toxemia in untreated animals. The
      subcutaneous injection of 1 per cent sodium chloride solution after release of
      the obstruction causes a rapid return of the blood to normal and allows the
      animal to recover. A similar amount of fluid given as 2 per cent glucose does not
      alter the course of the toxemia after release of the obstruction.

PMID- 19869510
TI  - THE BLOOD CHLORIDES IN PROTEOSE INTOXICATION.
AB  - Dogs injected with proteose recovered from the intestinal contents of animals
      with obstruction at different levels show no significant changes in the blood
      chlorides even with a fatal intoxication. After the intravenous injection of
      lethal and sublethal doses of Witte's peptone there is little change in the
      chlorides. Autolyzing liver in the abdominal cavity produces no change in the
      blood chlorides even with a very great increase in the urea and nonprotein
      nitrogen. Proteose intoxication is probably not a factor in the characteristic
      fall in chlorides seen after intestinal and pyloric obstruction.

PMID- 19869511
TI  - STUDIES ON A PARATYPHOID INFECTION IN GUINEA PIGS : V. THE INCIDENCE OF CARRIERS
      DURING THE ENDEMIC STAGE.
AB  - A group of 105 breeders and 36 unweaned guinea pigs was tested to determine the
      extent of specific fecal excretion and the proportion of serum reactors in a
      population naturally infected with two types of B. paratyphi. The second, more
      recent type of organism was isolated from the feces of 3 breeders and 3 young. No
      carriers of the first type were detected. 86 per cent of the breeders and 72 per
      cent of the unweaned guinea pigs agglutinated the second type of B. paratyphi in
      dilutions ranging from 1:10 through 1:640. 13 per cent of the breeders and 28 per
      cent of the unweaned young agglutinated the initial type. There was a cross or
      double agglutination in most instances. The serological findings roughly
      reflected the distribution of the two types as indicated by the mortality rate of
      the population at large. 50 breeders selected on the basis of agglutination and
      fecal examination and therefore supposedly free from infection were segregated
      and kept under close observation. Both types of B. paratyphi subsequently
      appeared in the group. During this time carriers were discovered by others in the
      Department among the stock guinea pigs used for other experiments in that
      cultures of the entire spleen were positive in perhaps 5 to 10 per cent of the
      guinea pigs so used.

PMID- 19869512
TI  - STUDIES IN THE BIOLOGY OF METALS : VII. THE INFLUENCE OF LEAD ON THE DEVELOPMENT
      OF THE CHICK EMBRYO.
AB  - OUR STUDY OF THE EFFECT OF THE LEAD ION ON THE DEVELOPMENT OF THE CHICK EMBRYO
      HAS BROUGHT OUT THE FOLLOWING FACTS: 1. Gross growth is retarded. 2. Somite
      growth is retarded to a degree greater than that exhibited by body length and
      width. 3. The head and optic anlagen are regions of particular sensitivity. Their
      differential development is markedly inhibited. From the purely biological point
      of view these results are in line with the findings of Child (10) and his school
      as to the sensitivity of the head end of rapidly growing organisms to harmful
      influences, and with those of Stockard (11) as to the peculiar sensitivity of the
      optic anlagen. It is almost too well known to need repetition that the head
      region and the somites of embryos are specific areas of intense growth by
      increase in cell number. Therefore, turning from the general to the particular,
      the differential retardation of these regions which is caused by lead, is
      evidence justifying the conclusion that it is areas of rapid growth by cell
      proliferation which are selectively inhibited by this metallic ion.

PMID- 19869513
TI  - STUDIES UPON THE EFFECT OF LIGHT ON BLOOD AND TISSUE CELLS : II. THE ACTION OF
      LIGHT ON ERYTHROCYTES IN VITRO.
AB  - 1. It was found that when hanging drops of whole blood, drawn from a rabbit, were
      subjected to irradiation from certain light sources, a striking degeneration of
      the white and of the red cells occurred. In this degeneration of the red cells
      there was (a) a preliminary period of 15-30 minutes during which no effect was
      noted; (b) following this, there was a period during which the cells swelled and
      became first almost biplanar, then biconvex, and finally spherical. After a
      spherical shape had been assumed, the liberation of blood pigment from the cells
      began. This process progressed with varied rapidity, sometimes being very slow,
      and being incomplete; sometimes being of almost explosive rapidity. This
      liberation was not accomplished in either case through a gross rupture of the
      cells, but through the agency of some submicroscopic change produced either in
      the cell contents, the cell wall, or both. Following this liberation of pigment,
      in some cultures the red cells showed signs of coagulation, as did the white
      cells. In other cultures, however, the red cells were reduced to achromatic
      shadows. 2. When whole blood was diluted with unbuffered Locke solution and then
      irradiated in hanging drop preparations, the erythrocytes swelled, as in whole
      blood, but then, instead of an almost instantaneous hemolysis of every cell
      present, or a slow liberation of hemoglobin from each individual cell, all the
      red cells hemolyzed, one or two at a time, the hemolyzed cells being left as
      achromatic shadows. 3. This hemolysis of the red cells, as in the case of the
      degeneration of the white cells, occurred upon irradiation of the culture with
      white light, or with light lying in each of the three spectral zones of the
      visual spectrum, defined by Wratten filters Nos. 45, 58 and 29 respectively, as
      follows: (a) 430micromicro-550micromicro; infra-red; (b) 475micromicro
      630micromicro; 690micromicro-infra-red; (c) 600micromicro-infra-red. 4. Within
      the range of intensities of light employed, there was little or no difference in
      the rate at which light of these three regions acted on the red cells. Further,
      this rate was the same as was the rate when the red cells were irradiated with no
      colored filter interposed in the optical path, or when a 5 per cent total
      transmission neutral filter was interposed. 5. It was shown that this
      degeneration of the red cells under the action of light was not dependent on the
      presence or absence of serum, with the possible exception of that trace which
      might have been adherent to the red cells even after repeated washing. 6. The
      white cells in the culture generally showed no changes until after traces of red
      cell pigment could be seen free in the surrounding medium. 7. On the other hand,
      no neutrophils were observed moving around for longer than a few minutes after
      the liberation of red cell pigment had occurred. 8. The liberation of substances
      from the red blood cells, as a result of irradiation of such preparations, may
      play some major role in the degeneration of irradiated white cells.

PMID- 19869514
TI  - STUDIES UPON THE EFFECT OF LIGHT ON BLOOD AND TISSUE CELLS : III. THE ACTION OF
      LIGHT ON FIBROBLASTS IN VITRO.
AB  - 1. In the presence of autogenous red blood cells, fibroblasts, grown in vitro
      from the heart and intestine of embryo chicks of from 6-12 days incubation,
      underwent a rapid degeneration when exposed to light of the visual spectrum. 2.
      In this degeneration, the cells showed a marked increase in refractive index, and
      a massive formation of colorless vacuoles of low refractive index. These vacuoles
      gave no reaction with osmic acid or Sudan III, but took up neutral red. Later in
      the degeneration the cells showed marked signs of rounding up and of coagulation.
      In some cases this degeneration process was modified in such a manner that,
      instead of the formation of vacuoles, the whole cytoplasm became much less viscid
      and the cells swelled greatly and became spherical. 3. The similarity of this
      degeneration to that shown by the erythrocytes, and more particularly, to that
      shown by the polymorphonuclear neutrophils, under the action of light, is pointed
      out. 4. Degeneration of the fibroblasts occurred when the cells were irradiated
      by light of any one of the following wave-length zones: (a) 430micromicro
      550micromicro; infra-red; (b) 475micromicro-630micromicro; 690micromicro-infra
      red; (c) 60micromicro-infra-red. 5. This degeneration was much slower for the
      cells irradiated through the blue or red filters of less than 5 per cent, and
      less than 6.6 per cent, respective total transmissions. When irradiated through
      the green filter of 23 per cent total transmission it was much more rapid, and
      even more rapid than for cultures irradiated with white light of 100 per cent
      total transmission. These data were obtained on a short series of cultures and
      must be considered only as suggestive. 6. In the apparent absence of red cells,
      the fibroblasts underwent only a slight degree of degeneration after irradiation
      lasting from 13-24(1/2) hours. It is possible that even this minor degeneration
      may depend upon the presence of traces of disintegration products of red cells in
      the culture. Much more advanced degenerative processes were obtained, when many
      red cells were present, after only 3 hours irradiation.

PMID- 19869515
TI  - EXPERIMENTAL PNEUMONIA IN GUINEA PIGS : I. THE EFFECT OF CERTAIN TOXIC
      AUTOLYSATES OF PNEUMOCOCCI.
AB  - 1. Anaerobic autolysates of pneumococci, prepared according to the method
      described, are highly toxic for guinea pigs when injected intratracheally in
      dosage of 0.2 cc. Death occurs either within a few hours (36 per cent) or within
      3 days. In the early deaths there is intense hemorrhagic edema of the lungs with
      beginning inflammatory reaction; in animals surviving for 18 hours or longer
      extensive areas of pneumonia are produced. 2. The intratracheal injection of
      virulent living pneumococci is followed by transient slight lesion with recovery,
      or by later death from septicemia without pneumonic lesions. 3. The addition of a
      sublethal dose of toxic autolysate to living pneumococci alters the reaction of
      the animal, so that there develops extensive pneumonia associated with
      unrestrained multiplication of the organism.

PMID- 19869516
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : XI. AN INQUIRY INTO THE MODE OF
      ACTION OF ANTIBACTERIOPHAGE SERUM.
AB  - 1. Each bacteriophage is a specific antigen. 2. The antibodies against the
      bacteriophage are independent of those against the bacterial substrate used in
      preparing the phage. 3. The reaction of neutralization is closely analogous to
      that of the neutralization of toxin by antitoxin. 4. The serum of mice
      experimentally infected with mouse typhoid (M.T.) did not become capable of
      neutralizing phages acting on the infecting organism. 5. The use of the reaction
      of neutralization of bacteriophage in the diagnosis of disease as proposed by
      Sonnenschein seems impractical.

PMID- 19869517
TI  - STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : XII. CONCERNING THE PRODUCTION OF
      PHAGE FROM BACTERIAL CULTURES.
AB  - 1. The phenomenon of phage production by one bacterial culture for another of
      different sort has been reproduced experimentally. 2. This phenomenon results
      from phage carried with the culture, and not from the spontaneous appearance of
      phage in a culture previously free from it. 3. Animals immunized against the
      lysogenic bacteria may develop antibodies that neutralize the phage carried. 4.
      The development of neutralizing antibodies on immunization with a bacterial
      culture is evidence of the presence of bacteriophage in the culture. 5. The
      failure of such antibodies to appear on immunization with bacteria does not
      necessarily indicate that bacteriophage is not present.

PMID- 19869518
TI  - ON THE INHERITANCE OF AGGLUTINOGENS OF HUMAN BLOOD DEMONSTRABLE BY IMMUNE
      AGGLUTININS.
AB  - The heredity of two agglutinable structures demonstrable by immune agglutinins
      was studied in 166 families. From the data collected it is evident that one deals
      with a case of Mendelian inheritance. The main result of the studies is the
      demonstration that it is feasible to investigate the heredity of serological
      structures of human blood other than the group agglutinogens. Irrespective of the
      ultimate theory it seems very probable that the properties M and N do not appear
      in the offspring when they are absent in both parents-a conclusion substantiated
      by the examination of ten families with 46 children. These findings offer the
      prospect of forensic application to cases of disputed paternity and, in our
      opinion, a correct decision could already be given, at least with great
      probability, provided the reagents are available and the method properly applied.
      Of course further work is needed before the test can be adopted as a routine
      procedure.

PMID- 19869519
TI  - VARIANTS OF HEMOLYTIC STREPTOCOCCI; THEIR RELATION TO TYPE-SPECIFIC SUBSTANCE,
      VIRULENCE, AND TOXIN.
AB  - Hemolytic streptococci, when freshly isolated from pathogenic lesions, form
      characteristic matt colonies and contain the type-specific substance M. Two
      varieties of matt cultures, equally rich in type-specific substance, can be
      distinguished by the virulence of the organisms for mice: (1) the matt virulent
      variety, (2) the matt attenuated variety. The matt forms of hemolytic
      streptococci can be degraded to a third variety which forms glossy colonies and
      is always relatively avirulent. This is accomplished by prolonged cultivation on
      artificial media, by selection of colonies or by cultivation in homologous anti-M
      serum. In the process of degradation the cocci lose the major part of their type
      specific substance but complete disappearance of type-specific substance rarely
      occurs. The glossy variant form, when fully degraded, is highly stable; but
      glossy cultures which have retained some type-specific substance can occasionally
      be reverted to the original matt form. Toxic filtrates from matt and glossy
      cultures are approximately equal in skin reactivity. No relationship appears to
      exist between virulence and toxigenicity.

PMID- 19869520
TI  - ANTIGENIC DIFFERENCES BETWEEN MATT HEMOLYTIC STREPTOCOCCI AND THEIR GLOSSY
      VARIANTS.
AB  - The matt and the glossy forms of four strains of hemolytic streptococci were used
      to immunize rabbits. Precipitin tests showed that rabbit sera prepared against
      matt organisms, whether virulent or avirulent for mice, contained type-specific
      antibody while sera prepared against completely degraded glossy organisms
      contained no type-specific antibody. Type-specific antibody was removed from the
      sera by absorption with homologous matt organisms but was unaffected by
      absorption with homologous glossy organisms. Passive protection experiments on
      mice showed that anti-matt sera were protective and anti-glossy sera non
      protective against infection with homologous virulent organisms. Vaccination of
      mice with matt organisms rendered them immune to subsequent infection with
      homologous virulent cultures; but vaccination with glossy organisms established
      no active immunity.

PMID- 19869521
TI  - ACTIVE AND PASSIVE IMMUNITY TO PNEUMOCOCCUS INFECTION INDUCED IN RABBITS BY
      IMMUNIZATION WITH R PNEUMOCOCCI.
AB  - 1. Rabbits, vaccinated by repeated intravenous injections of suspensions of heat
      killed R pneumococci, acquire a marked degree of active immunity to infection
      with the virulent S forms of Pneumococcus Types I and II. Previously (1) it was
      shown that the immunization of rabbits with R cells induces active resistance to
      Type III infection. This immunity is effective when the infecting organisms are
      injected either intravenously, intraperitoneally, or intradermally. 2. Whole
      citrated blood or serum of rabbits immunized with R pneumococci, under the
      experimental conditions described, is capable of passively protecting normal
      rabbits against Type I and Type III infection. Whole blood appears to be more
      effective than an equivalent amount of serum. 3. Passive protection of mice by
      the use of whole blood or serum of the immune rabbits has been entirely
      ineffectual. This is in striking contrast to the results obtained with type
      specific immune serum. 4. This form of acquired resistance to pneumococcus
      infection, elicited by R organisms which are devoid of type specificity, and
      exemplified in animals whose sera possess no demonstrable type-specific
      antibodies, has many characteristics strongly suggesting that the underlying
      mechanism differs from that concerned in type-specific immunity.

PMID- 19869522
TI  - SUPPRESSION OF THE FIRST ATTACK WITH SUBSEQUENT RELAPSE: AN IMMUNE PHENOMENON IN
      EXPERIMENTAL RELAPSING FEVER.
AB  - In five splenectomized squirrels and chipmunks which were reinoculated with a
      strain of Spironema recurrentis which had previously been present in their blood,
      the first attack was entirely suppressed because the animals were immune to the
      strain of spirochetes inoculated; but after the interval which usually occurred
      between attacks, a relapse ensued, in which the strain of spirochetes present in
      the blood was different from the strain inoculated.

PMID- 19869523
TI  - OBSERVATIONS ON FLAGELLAR AND SOMATIC AGGLUTINATION.
AB  - Whole, shaken and heated suspensions of two Salmonella species were compared as
      to agglutinability, absorptive capacity and antigenic properties. The results
      were in general agreement with the flagellar antigen concept of Smith and Reagh.
      The removal of flagella by shaking or heating (100 degrees C.) resulted in
      altered agglutinability manifested by failure to give a floccular reaction with
      "whole" antiserum. The deflagellated bacteria were able to absorb some
      flocculating agglutinin from that serum. They were unable, however, to produce
      flocculating agglutinin upon injection in rabbits. Untreated, shaken and heated
      suspensions of a non-motile bacterium (Staphylococcus) showed no differences with
      respect to agglutinability or absorptive capacity. Soluble precipitable material
      was found present in small amount in culture filtrates of the motile bacteria and
      in greater concentration in filtrates of heated suspensions. The bulk of the
      soluble material was of somatic origin and was not appreciably increased by the
      presence of flagella. It was possible, however, to demonstrate soluble material
      in heated flagellar suspensions. The relation of such soluble substances to
      floccular agglutination and the production of flocculating agglutinin as
      suggested by Hadley is discussed.

PMID- 19869524
TI  - THE REMOVAL OF AGGLUTININ FROM SENSITIZED MOTILE BACTERIA.
AB  - It was shown that flocculating (flagellar) agglutinin and granulating (somatic)
      agglutinin display certain differences with respect to their removal from
      sensitized bacteria (B. paratyphi). A 5 per cent solution of NaCl added to
      sedimented, sensitized bacteria followed by heating to 60 degrees C. for 1 hour
      removed approximately 50 per cent of the combined agglutinin. There was little or
      no removal of granulating agglutinin either from the sensitized motile bacteria
      or from a sensitized non-motile organism (Staphylococcus). Evidence was presented
      that the agglutinin removal was not dependent solely on disintegration of
      flagella by the conditions of extraction with a subsequent freeing of antibody.

PMID- 19869525
TI  - THE ACID-BASE COMPOSITION OF GASTRIC SECRETIONS.
AB  - The chief inorganic factors in secretions obtained from isolated pouches
      constructed in the fundus and in the pyloric antrum of the cat's stomach were
      found to be chloride ion and fixed base. In a series of samples obtained from the
      fundic pouch, chloride ion was approximately stationary at 165 cc. 0.1 N per 100
      cc. During digestion of food in the stomach, secretions from the pouch contained
      fixed base in amounts varying considerably from an average of 47 cc. 0.1 N per
      100 cc. Material allowed to remain in the pouch after the completion of food
      digestion in the stomach showed an increasing content of fixed base, to as much
      as 140 cc. 0.1 N per 100 cc. A stationary total ionic content of secretions of
      the fundus is thus seen to be sustained by the chloride ion concentration, and
      changes in hydrogen ion concentration to be caused by variation of fixed base.
      The differing amounts of fixed base found are regarded as probably due to
      admixture of a mucous secretion with the juice from the fundic glands. The
      alkaline secretion taken from a pyloric pouch contained fixed base in excess of
      chloride ion. Variation of fixed base in the secretions from the fundic pouch
      were found to be referable to change in sodium content, the smaller factor,
      potassium, remaining approximately constant at about the value found in material
      from the pyloric pouch. This suggests that the mucous secretion of the fundus has
      the same composition as that produced by the pyloric antrum. These data will
      serve to explain the extensive withdrawal of fixed base, as well as of chloride
      ion, from the blood plasma in the presence of circumstances causing a continued
      loss of stomach secretions.

PMID- 19869526
TI  - ACID-BASE COMPOSITION OF PANCREATIC JUICE AND BILE.
AB  - Pancreatic juice contains fixed base at approximately the concentration found in
      the blood plasma. Chloride ion is present in concentrations varying from one
      fourth to one-half the fixed base value and the remainder of the acid equivalence
      is composed of bicarbonate ion. Fixed base being a nearly stationary factor,
      variation of bicarbonate and thereby of alkalinity is referable to change in the
      concentration of chloride ion. In bile, as delivered by the liver, both the fixed
      base and chloride ion values correspond closely with their respective
      concentrations in blood plasma. In gall bladder bile, however, the concentration
      of fixed base is, roughly, double that in hepatic duct bile, and chloride ion has
      been almost entirely removed. From these data it may be inferred that loss of
      digestive secretions entering the duodenum will, in the absence of replacement of
      the materials contained, cause dehydration of the blood plasma and reduction of
      the plasma bicarbonate.

PMID- 19869527
TI  - BODY FLUID CHANGES DUE TO CONTINUED LOSS OF THE EXTERNAL SECRETION OF THE
      PANCREAS.
AB  - From the data given above the following explanation of the effects of continued
      loss of the external secretion of the pancreas may be offered. The underlying
      event is a steadily increasing deficit of sodium and of chloride ion due to the
      large requirement for these electrolytes in the construction of pancreatic juice.
      In consequence there is continued loss of water, chiefly from the body fluids in
      which sodium and chloride ion are large factors of total ionic content, viz.,
      interstitial fluids and the blood plasma. During about two-thirds of the survival
      period the volume and composition of the blood plasma remain approximately
      normal, the losses of water, sodium, and chloride ion being replaced at the
      expense of interstitial fluids. Reduction of the volume of these fluids is
      indicated by loss of body weight beginning directly after establishment of the
      pancreatic fistula. Ultimately reduction of plasma volume begins and, as it
      progresses, serious symptoms develop and death occurs unless water, sodium, and
      chloride ion are abundantly replaced. Owing to the relatively greater loss of
      sodium than of chloride ion in pancreatic juice, reduction of bicarbonate ion
      concentration in the plasma tends to occur. The death of the organism may be
      simply and reasonably explained as the result of progressive impairment of the
      function of the blood by the physical changes, dehydration and acidosis, produced
      in the plasma by the continued loss of sodium and of chloride ion in the
      pancreatic juice.

PMID- 19869528
TI  - STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS : VII. EXTRACORPOREAL
      THROMBOSIS IN EXPERIMENTAL OBSTRUCTIVE JAUNDICE AND AFTER THE INTRAVENOUS
      ADMINISTRATION OF BILE ACIDS.
AB  - In experimental obstructive jaundice in rabbits, thrombosis is definitely delayed
      in the extracorporeal loop. White thrombi are laid down at the normal rate in
      many instances; in others there is a delay in deposition of platelets, while in
      still others cauliflower-like masses of platelets are rapidly deposited and tend
      to slow or even stop the blood stream before much fibrin is apparent. Fibrin
      deposits and formation of the red thrombus usually appear late in the experiment
      and often only at the ends of the collodion tubes. In vigorous animals, the
      thrombi rarely tend to obstruct and usually cease growing when they have made up
      the difference between the lumen of the glass tube and of the collodion tube. On
      the other hand, if the animal's general condition is poor and its circulation
      depressed, red thrombus forms more rapidly and tends to encroach progressively on
      the lumen until obstruction takes place. Even in such cases circulation through
      the loop persists for periods much longer than in the normal animal. Judging from
      the gross appearance of the thrombus the quantity and quality of fibrin seem
      deficient. Single injections of bile salts yield pictures similar to those seen
      in experimental obstructive jaundice. White thrombi are deposited but obstruction
      of the lumen is delayed because of inadequate formation of fibrin. The continuous
      intravenous injection of bile salts resulted in a progressive increase of the
      clotting time and in the level of bile acids of the blood. The state of the
      extracorporeal loop was likewise similar in many respects to that seen in
      obstructive jaundice. There was, however, a definite decrease in the size and
      numbers of white thrombi deposited on the collodion membrane. From the evidence
      presented it is obvious that the processes of blood coagulation and of thrombosis
      in the extracorporeal loop are definitely delayed in experimental obstructive
      jaundice and in animals that have received intravenous injections of bile salts.
      No attempt is made to explain the changes found in jaundice on the basis of the
      increased levels of bile acids in the blood although these experiments would
      indicate that such a possibility has not been ruled out.

PMID- 19869529
TI  - THE PRODUCTION OF EXPERIMENTAL TYPHOID FEVER IN THE GUINEA PIG WITH AN IN VIVO
      PREPARED TOXIC FILTRATE OF B. TYPHOSUS.
AB  - When the typhoid bacillus is injected into the peritoneal cavity of guinea pigs
      acute peritonitis and death are produced. The character of the exudate is
      variable as to the elements present but is usually of a serous type with slight
      clouding due to the presence of polymorphonuclear neutrophils, mononuclear cells
      and bacteria. When the Berkefeld filtrate of this exudative material is
      inoculated into normal guinea pigs either subcutaneously, intraperitoneally or
      intracardially, the character of response obtained on the part of the host is
      quite at variance with that produced by the inoculation of the living typhoid
      bacillus. A febrile reaction and marked leucopenia, as a rule, are persistent and
      are accentuated after each injection the latter often reaching below 1000 cells
      per c. mm. There is a loss of weight of a variable extent in all animals and in
      some the emaciation is extreme. The animals were given four such inoculations and
      all succumbed in from 2 to 4 weeks. The intracardiac route produces death more
      quickly and the reactions are more clear-cut when this route is employed. At
      autopsy a general tumefaction and congestion of the lymphoid structures more
      especially of the abdominal cavity are found. Peyer's patches and the solitary
      follicles of the intestinal tract are likewise involved and in some of the
      patches slight ulceration is noted; occasionally, there occur extreme ulceration
      and necrosis of the patch. The spleen is enlarged and usually softened.
      Microscopically, marked endothelial cell proliferation is noted especially in the
      lymphoid structures and in many instances the phagocytic cells of Mallory are
      found. These cells include within their cytoplasm elements of the surrounding
      structures. In the spleen there are present congestion, and hemorrhages with many
      "shadow" red blood cells. Phagocytosis of the red cells by the endothelial cells
      is present. In the liver, areas of focal necrosis are found and phagocytic cells
      are seen. In the animals inoculated subcutaneously, localized degenerative
      changes are observed especially in the muscular structures. From these results it
      can be seen that the reactions and injury of the animal body by the toxic
      filtrate employed, are quite similar to the changes produced by the specific
      toxin in human typhoid fever.

PMID- 19869530
TI  - A NOTE ON THE FILTRATION OF THE VIRUS OF HERPETIC ENCEPHALITIS AND OF VACCINIA.
AB  - The virus of herpetic encephalitis and the virus of vaccinia can be demonstrated
      in the filtrate, if a broth emulsion of fresh tissue containing the virus, is
      passed through a Berkefeld V filter.

PMID- 19869531
TI  - CALCIUM AND INORGANIC PHOSPHORUS IN THE BLOOD OF RABBITS : IV. INFLUENCE OF LIGHT
      ENVIRONMENT ON NORMAL RABBITS.
AB  - A series of experiments was carried out for the purpose of determining whether a
      light environment comprising radiations of comparatively long wave-length and
      only a small amount of energy was capable of affecting the chemical equilibrium
      of the blood as indicated by the calcium and inorganic phosphorus content of the
      blood of normal rabbits. A study was made of effects produced by prolonged
      exposure to fixed environmental conditions (neon light and darkness) as compared
      with a varying environment of diffuse, filtered sunlight and by a change from one
      environment to another. It was found that the chemical equilibrium of the blood
      was definitely affected by the conditions employed and that the effects produced
      could be correlated with differences in organic constitution on the one hand, and
      on the other, with certain differences in the functional activity of the same
      animals, involving nutrition and growth and the proliferative activity of hair
      follicles.

PMID- 19869532
TI  - STUDIES ON THE SENSITIZING PROPERTIES OF THE BACTERIOPHAGE.
AB  - 1. Marked specific contractions of the uterine horns of guinea pigs, actively
      sensitized, to phage-lysed Flexner bacilli or to colon bacilli, lysed by the same
      bacteriophage, occurred on testing either series for anaphylaxis with the
      homologous phage lysates. These reactions, however, were not due to an antigenic
      function of the bacteriophage itself, because no reaction whatsoever occurred
      when the same bacteriophage, propagated on the heterologous organisms, was
      substituted in the anaphylactic test. 2. Specific uterine reactions of marked
      intensity were obtained in guinea pigs, actively sensitized to intact or
      autolyzed Flexner or colon bacilli, respectively, by testing either series for
      anaphylaxis with homologous, phage-free bacterial antigens. 3. No reaction
      occurred by testing the uterine strips of animals, sensitized to intact or
      autolyzed bacilli (either Flexner or coli), for anaphylaxis with homologous phage
      lysates and, vice versa, there was no contraction of uterine strips sensitized to
      phage lysates upon contact with homologous bacterial autolysates. 4. The
      observations made in this paper suggest that a new and immunologically distinct
      antigenic complex arises from the bacterial protein after lysis of the organisms
      by the bacteriophage.

PMID- 19869533
TI  - STUDIES OF CALCIUM AND PHOSPHORUS METABOLISM : V. A STUDY OF THE BONE TRABECULAE
      AS A READILY AVAILABLE RESERVE SUPPLY OF CALCIUM.
AB  - 1. Bone trabeculae are easily depleted by the prolonged administration of
      parathormone, long continued negative calcium balance and growth. 2. A long
      continued high calcium diet results in a rapid accumulation of the trabeculae. 3.
      Alizarin red, as has previously been shown in the literature, is deposited in
      newly formed bone. Its use has made clear that easily mobilizable calcium is not
      deposited in the shafts of adult animals, but in the trabeculae of bone. 4. The
      bone trabeculae therefore serve as the storehouse of readily available calcium.
      5. The shafts have a slow progressive exchange of inorganic salts and are not
      influenced except in the case of unusual body demands. 6. It is suggested that
      the absence of trabeculae in premature infants and their depletion at the end of
      4 months in a normal baby might well be an etiological factor in rickets. 7. In
      our observations, parathormone administration to growing or adult cats has been
      without effect. 8. Daily injections of parathormone in growing rats results in an
      increased number of trabeculae and smaller bones.

PMID- 19869534
TI  - STUDIES IN ASTHMA : VII. THE PULMONARY CIRCULATION IN THE GUINEA PIG DURING
      ANAPHYLACTIC SHOCK.
AB  - 1. Sheep serum in doses below 0.3 cc. intravenously produces no pulmonary
      vasoconstriction in the guinea pig. Guinea pigs have consequently been sensitized
      with this substance and anaphylactic shock produced by doses of O.1 and 0.2 cc.
      2. Pressure in the pulmonary artery has been measured by the method of Drinker
      and Went (2) and recorded photographically in a new and convenient manner. 3. At
      a very early stage in anaphylactic shock the pulmonary arterial pressure falls
      markedly and this fall seems to precede the appearance of bronchiolar
      obstruction. 4. The fall in pulmonary blood pressure in anaphylactic shock is in
      marked contrast to the rise in pressure resulting from intravenous injection of
      toxic foreign protein, such as horse serum.

PMID- 19869535
TI  - STUDIES ON HYPERSENSITIVENESS TO DIPHTHERIA BACILLI : I. AN "IMMEDIATE" SKIN
      REACTION WHICH CAN BE PASSIVELY TRANSFERRED.
AB  - The paper describes an "immediate" skin reaction to derivatives of the diphtheria
      bacillus which is shown to be distinct from the "delayed" or "pseudoreaction"
      commonly seen in Schick tests on adults. The "immediate" reaction was passively
      transferred to local areas of the skin of other people.

PMID- 19869536
TI  - A CHEMICAL AND PATHOLOGIC STUDY OF THE EFFECTS OF COPPER ON THE LIVER.
AB  - FROM THE ABOVE STUDIES THE FOLLOWING CONCLUSIONS HAVE BEEN REACHED: 1. That
      copper or its compounds used does not cause the deposition of pigment in the
      livers of rabbits, guinea pigs or rats. Neither does it produce a cirrhosis in
      these animals. 2. That spontaneous deposition of pigment occurs frequently in the
      livers of normal rabbits on the usual laboratory diet. 3. That the feeding of a
      diet of carrots exclusively will produce pigment deposition in the livers of
      rabbits, in every way identical with that ascribed to copper. 4. That the pigment
      deposited in the livers of rabbits is probably of exogenous origin.

PMID- 19869537
TI  - THE GERMICIDAL AND HEMOLYTIC ACTION OF alpha-BROM SOAPS.
AB  - 1. The soaps of the alpha-brom fatty acids are usually more germicidal than the
      unsubstituted soaps. Only when B. typhosus was the test organism was there no
      increase in germicidal action. 2. For any test organism, germicidal action of the
      brominated soaps increases rapidly with increasing molecular weight up to a
      certain point, then diminishes. This is likewise true of the hemolytic titer. The
      point of maximal germicidal action varies with the different species of tests
      organisms. In the series studied, brominated soaps of 12 and 14 carbon atoms were
      most germicidal for the Gram-negative organisms, while soaps of 16 and 18 carbon
      atoms were most germicidal for Gram-positive organisms. 3. The brominated soaps
      are, in general, more active in acid that in neutral or alkaline reactions. The
      reasons for this have been discussed in a previous paper, in which a similar
      phenomenon with unsubstituted soaps was observed. 4. For certain organisms, the
      brominated soaps are among the most rapid and potent germicides known.

PMID- 19869538
TI  - STUDIES ON FOWL PARALYSIS (NEUROLYMPHOMATOSIS GALLINARUM) : I. CLINICAL FEATURES
      AND PATHOLOGY.
AB  - 1. Fowl paralysis (neurolymphomatosis gallinarum) is a disease entity, with
      characteristic clinical and pathological features. 2. The disease occurs in all
      parts of the United States, Holland, Austria and probably South America. 3. The
      disease appears to be endemic in certain foci. Having once appeared, the disease
      tends to persist through successive years. 4. It occurs with about equal
      frequency in both sexes; all common breeds may be affected. 5. Symptoms appear
      between the 3rd and 18th months. Typical clinical cases have not been observed
      outside of these limits. 6. The conspicuous symptoms are (a) asymmetrical,
      partial and progressive paralysis of the wings and both legs, and rarely of neck
      muscles; (b) occasional grey discoloration of iris, with blindness. Nutrition is
      usually preserved. 7. The duration is variable; the outcome is usually fatal, but
      spontaneous recovery may rarely occur. 8. The principal pathological changes are
      found in the nervous system. In the peripheral nerves, the essential feature is
      an intense infiltration of lymphoid, plasma cells, and large mononuclears. This
      is accompanied by a myelin degeneration in the more advanced lesions, but the
      cellular infiltrations appear to precede the degenerative changes. In brain, cord
      and meninges, there are similar infiltrations predominantly perivascular.
      Infiltrations of the iris with lymphoid and plasma cells are found in the cases
      showing gross discoloration of the iris. Visceral lymphomata, originating usually
      in the ovary, are associated in a certain percentage of the cases. Evidence is
      presented in favor of the view that this association is not accidental, and that
      the lymphomata are a manifestation of the disease. 9. Infiltrations of the spinal
      cord and brain, rarely of the peripheral nerves, are frequently present in birds
      showing no clinical symptoms. These are interpreted as mild cases of the same
      disease. 10. No microorganisms of etiological significance have been demonstrated
      in the tissues or by cultural methods.

PMID- 19869539
TI  - STUDIES ON FOWL PARALYSIS (NEUROLYMPHOMATOSIS GALLINARUM) : II. TRANSMISSION
      EXPERIMENTS.
AB  - 1. Inoculation of suspensions of brain, cord, ganglia or nerves of chickens with
      neurolymphomatous lesions, into newly hatched chicks, is followed by the
      development of typical lesions in approximately 25 per cent of cases. 2. In
      control chickens kept under laboratory conditions the incidence of the disease is
      about 7 per cent. 3. The disease does not become manifest until at least 2 months
      after inoculation; symptoms may not appear until after 4 months. 4. The active
      agent is not destroyed by 50 per cent glycerol in 9 days at ice box temperature.

PMID- 19869540
TI  - THE CHEMICAL NATURE OF THE SUBSTANCES REQUIRED FOR CELL MULTIPLICATION : II.
      ACTION OF GLUTATHIONE, HEMOGLOBIN, AND ASH OF LIVER ON THE GROWTH OF FIBROBLASTS.
AB  - 1. It has been shown that the ash of liver, hemoglobin, and glutathione each
      exerts a very slight beneficial effect on the growth of sarcomatous fibroblasts
      of the rat, or on the condition of their cells when cultivated in a synthetic
      medium. 2. The addition of all three of these substances, or of only glutathione
      and hemoglobin, to a mixture of casein digest, glycocoll, and nucleic acid gives
      a medium in which sarcomatous fibroblasts of the rat proliferate for a
      considerable time as rapidly as in embryo juice. 3. The mixture is not as
      adequate a nutritive medium as embryo juice, for after a time dead cells are
      found surrounding the central fragment of the culture, and after several passages
      the growth becomes thinner. 4. The hypothesis is suggested that glutathione and
      hemoglobin may function not only by regulating the respiration and oxidation
      reduction reactions within the cell, but also by regulating the oxidation
      reduction potential of the medium. 5. It is suggested that the failure to obtain
      growth of fibroblasts in mixtures of amino acids or of the products of complete
      acid hydrolysis of proteins is in part due to the absence of glutathione, and
      that this substance is not synthetized by fibroblasts. 6. The growth of normal
      fibroblasts of the rat is also increased by the addition of the above mentioned
      substances to a synthetic medium.

PMID- 19869541
TI  - STUDIES ON IMMUNOLOGICAL RELATIONSHIPS AMONG THE PNEUMOCOCCI : III. RELATIONSHIP
      BETWEEN A VARIETY OF SACCHAROMYCES CEREVISIAE AND THE TYPE II VARIETY OF
      DIPLOCOCCUS PNEUMONIAE (PNEUMOCOCCUS).
AB  - The paper reports evidence of an immunological relationship between one variety
      of Saccharomyces ceremsise and the Type II variety of Diplococcus pneumonix
      (Pneumococcus). The most convincing data consisted of the reactions of the Type
      II bacteria with potent antiyeast serum which agglutinated, and protected mice
      against these pneumococci as well as the average antiserum obtained by
      immunization of rabbits with Type II bacteria themselves. The reactivity of the
      antiyeast serum is strictly specific to the Type II variety of Pneumococcus in
      the sense that it is entirely devoid of antibodies reactive with Type I or III.
      The results of absorption experiments with both the antiyeast (rabbit) serum and
      the anti-Type II (horse) serum were the same as those usually obtained in
      analogous experiments with immunologically related, but not identical, kinds of
      bacteria. The immunological relationship of the yeast and the Type II
      pneumococcus is apparently based upon S-anti-S reactions. It represents an
      example of heterogenetic specificity which is of particular interest because of
      the wide genetic separation of the pathogenic schizomycete and the saprophytic
      ascomycete. Data on the individual irregularity in the yeast-agglutinating
      capacity of serum from non-immunized or "normal" rabbits are presented as
      experimental facts.

PMID- 19869542
TI  - AN EXPERIMENTAL STUDY OF THE ETIOLOGY OF CHICKEN SARCOMA I (ROUS).

PMID- 19869543
TI  - BLOOD REGENERATION IN SEVERE ANEMIA : XIV. A LIVER FRACTION POTENT IN PERNICIOUS
      ANEMIA FED ALONE AND COMBINED WITH WHOLE LIVER, LIVER ASH AND FRESH BILE.
AB  - A liver extract No. 343, N.N.R. known to be fully potent in pernicious anemia
      shows but 10 to 20 per cent of the potency of whole liver feeding in severe
      continuous secondary anemia due to bleeding in dogs. There are wide individual
      variations which are not noted with whole liver feeding. Supplementing this liver
      extract with whole bile does not modify the reaction. Supplementing this liver
      extract with liver ash or apricot ash shows the sum of the two expected feeding
      reactions. When we supplement this liver extract with small amounts of whole
      liver (50 to 100 gm.) we may observe hemoglobin and red cell production in excess
      of the sum of the expected separate reactions. Whether the liver extract
      increases the potency of the whole liver feeding or vice versa, it suggests
      similar possibilities in various human secondary anemias. Liver and kidney
      fractions of varied types deserve much study to ascertain their effect upon
      widely divergent types of human anemias.

PMID- 19869544
TI  - STUDIES ON THE SUBMAXILLARY VIRUS OF GUINEA PIGS : I. THE EFFECT OF DUCT LIGATION
      AND PILOCARPINE ADMINISTRATION UPON THE CELLULAR RESPONSE TO THE VIRUS.
AB  - The development in the submaxillary glands of guinea pigs ol intranuclear
      inclusions traceable to submaxillary virus can be wholly suppressed by ligation
      of the gland ducts. Inclusions appear in fai greater numbers in glands stimulated
      with pilocarpine than is the case in ordinary spontaneous and induced infections.

PMID- 19869545
TI  - THE REVERSION OF R TO S PNEUMOCOCCI.
AB  - A study was made of the behavior of R pneumococcus strains under various
      experimental conditions. It was found that daughter colonies frequently appeared
      among the R forms and in some instances tended to replace the typical R forms.
      The daughter strain produced colonies with shiny surfaces which were
      morphologically indistinguishable from genuine S colonies although the
      characteristics of the bacteria comprising them conformed to the R variety. Both
      R and daughter forms which had resided for long periods of time in vivo have been
      converted into virulent forms. Strains of R pneumococci which seemed irreversible
      were apparently converted into S forms by applying the methods of Griffith. A
      general consideration of the information derived during the recent experimental
      studies indicates that virulent S pneumococci may dissociate into the R form in
      vivo, that the R forms may be occasionally found in the sputum of pneumonia
      patients and also may reside or lie dormant in vivo for a considerable period of
      time. It has been shown that under favorable circumstances bacteria of the R form
      may spontaneously revert to the original S form or by special methods may even
      transform into S forms of another type.

PMID- 19869546
TI  - ANAPHYLAXIS WITH THE TYPE-SPECIFIC CARBOHYDRATES OF PNEUMOCOCCUS.
AB  - 1. The type-specific carbohydrates (haptens) of Pneumococcus Types I, II and III,
      when isolated in protein-free form, are devoid of the property of inducing active
      anaphylactic sensitization in guinea pigs. 2. The bacterial carbohydrates of
      Pneumococcus, of which the Type II and Type III substances are nitrogen-free,
      produce rapid and fatal anaphylactic shock in guinea pigs passively sensitized
      with the precipitating serum of rabbits immunized with pneumococci of the
      homologous type; the reactions induced are type-specific. 3. In contrast to the
      positive results with immune rabbit serum, there is a complete absence of
      anaphylactic response to pneumococcus carbohydrate in guinea pigs passively
      sensitized with antipneumococcus horse serum.

PMID- 19869547
TI  - A STUDY OF PNEUMOCOCCUS AUTOLYSIS.
AB  - 1. Autolysis of Pneumococcus is accompanied by proteolysis, which results in an
      increase in amino and non-coagulable nitrogen. 2. Autolysis of Pneumococcus is
      accompanied by lipolysis during which there is a liberation of ether-soluble
      fatty acids. 3. When extracts containing the active intracellular enzymes are
      added to heat-killed pneumococci, lysis of the cells occurs and there is an
      increase in the non-coagulable and amino nitrogen, comparable to the changes
      accompanying spontaneous autolysis. 4. When extracts containing the active
      intracellular enzymes are added to emulsions of the alcohol-soluble lipoids
      extracted from pneumococci, an increase in the ether-soluble fatty acid occurs.
      5. Sodium desoxycholate in excess inhibits the action of pneumococcus protease;
      it does not inhibit the action of pneumococcus lipase. 6. When suspensions of
      pneumococci are cooled to 0 degrees C., a temperature at which the rate of enzyme
      action is greatly retarded, the organisms go into solution rapidly when sodium
      desoxycholate is added, but this process is not accompanied by lipolysis or
      proteolysis. It does not seem probable, therefore, that the "bile" solution of
      pneumococci is identical with the phenomenon of autolysis as ordinarily
      understood and measured. 7. The relation of enzyme action to antigenic
      dissociation is discussed.

PMID- 19869548
TI  - BIOMETRY OF CALCIUM, INORGANIC PHOSPHORUS, CHOLESTEROL, AND LIPOID PHOSPHORUS IN
      THE BLOOD OF RABBITS : II. REPEATED OBSERVATIONS ON NORMAL ANIMALS.
AB  - A series of determinations of inorganic phosphorus, calcium, cholesterol, and
      lecithin were made on a group of 10 animals living in the laboratory from Oct.
      27, 1927, to May 17, 1928. A marked difference in both the trend and absolute
      values was noted in animals living in the laboratory when compared with the
      values obtained for animals living out-of-doors. With animals living in the open,
      the trend of variation for calcium was found to be the same. However, animals
      living in the laboratory maintained a higher level over the same period of time.
      The inorganic phosphorus and lecithin both showed a marked decrease and both
      maintained a lower level than was found in animals just received from the dealer.
      The cholesterol content of whole blood exhibited a similar trend in both groups
      of animals. However, it was found that animals living in the laboratory
      maintained a lower level than animals living out-of-doors. The mean value for
      calcium was found to be 15.7 +/-0.05, for inorganic phosphorus 4.65 +/-0.05 mg.
      per 100 cc. of blood serum, and for cholesterol 58.2 +/-0.39 and lecithin 118.4
      +/-1.13 mg. per 100 cc. of whole blood. The coefficients of correlation having
      the highest degree of mathematical significance were obtained from the mean
      values for individual animals.

PMID- 19869549
TI  - THE RELATION OF FREQUENCY TO THE PHYSIOLOGICAL EFFECTS OF ULTRA-HIGH FREQUENCY
      CURRENTS.
AB  - 1. Biological effects of electromagnetic waves emitted by a vacuum tube
      oscillator have been studied at frequencis ranging from 8,300,000 to 158,000,000
      cycles per second (1.9 to 38 meters wave-length). 2. The effects produced on
      animals can be fully explained on the basis of the heat generated by high
      frequency currents which are induced in them. 3. No evidence was obtained to
      support the theory that certain wave-lengths have a specific action on living
      cells. 4. At frequencies below 50,000,000 cycles, the effect of these radiations
      on animals is proportionate to the intensity of the electro-magnetic field. As
      the frequency is increased beyond this point, the amount of induced current is
      diminished and the apparent lethality of the radiation is decreased. This can be
      explained by changes occurring in the dielectric properties of tissues at low
      wave-lengths.

PMID- 19869550
TI  - MATERIAL FROM LYMPH NODES : IV. THE HETEROLOGY OF LYMPHOID TISSUE WITH SPECIAL
      REFERENCE TO THE MONOCYTE-SUPRAVITAL STUDIES.
AB  - 1. Lymph nodes from all parts of the body have been studied in a series of 58
      rabbits. All of these studies have been on normal animals or on animals in which
      there were no specific pathologic lesions of the lymph nodes. 2. The supravital
      method of studying living cells has been employed together with the method of
      fixed sections. A correlation of the findings with these two methods is made. 3.
      Lymph nodes from different parts of the body possess marked differences in their
      cytology. 4. Developing monocytes have been found as normal constituents of all
      the lymph nodes of the rabbit except the mesenteric mass lying in the mesentery
      at the lower border of the stomach. When present the monocytes occur in varying
      numbers being most abundant in the more superficial nodes, particularly in the
      popliteal group, where they may constitute one-third to one-half of the total
      cells present. 5. The position of the developing monocytes in the lymph node is
      believed to be chiefly in the perifollicular area without definite relationship
      to the lymph sinuses. In some instances they are also found in the follicle
      itself or scattered in the medullary area. More accurate knowledge on this point
      must await further study. 6. During the first hours of life the monocytes are
      present in the lymph nodes in the same relationship as in the adult animal. 7.
      The monocytes are not normally present in the efferent lymphatics draining the
      popliteal nodes and are not normally present in the thoracic duct. It is
      suggested that the monocytes being extravascular in origin, enter the blood
      stream by means of their own motility in much the same manner as the granular
      leucocytes gain admission to the circulating blood. Unequivocal proof of this
      point can be obtained only by further investigation. 8. Many of the lymphoid
      cells of the lymph nodes have shown a definite division of cytoplasm into
      ectoplasm and endoplasm. The mitochondria and neutral red bodies are sharply
      limited to the less basophilic endoplasm. 9. Eosinophils are found in great
      numbers in the mediastinal lymph nodes and are less numerous in the mesenteric
      and superficial nodes. 10. Clasmatocytes are found in great numbers in the
      mesenteric lymph nodes where they are concentrated particularly in the medullary
      areas. They are also present in the spleen. They are much less numerous in other
      lymphoid tissue. 11. Several cell types not previously described are found to be
      normal constituents of a large percentage of normal rabbit lymph nodes. 12.
      Primitive cells are found throughout the lymphoid tissue, but are in greater
      numbers in the area of the germ center of the follicle. 13. No evidence of
      erythropoiesis could be found in normal lymph nodes. 14. The spleen and bone
      marrow in this series of animals have not been normally concerned to any
      significant degree in the formation and development of monocytes. 15. Further
      experiments are necessary to demonstrate conclusively whether or not the lymph
      nodes, other than the mesenteric group, are normally the exclusive source of the
      monocytes of blood.

PMID- 19869551
TI  - STUDIES OF THE LYMPHATIC TISSUE : III. EXPERIMENTAL STUDIES OF THE RELATION OF
      THE LYMPHATIC TISSUE TO THE NUMBER OF LYMPHOCYTES IN THE BLOOD IN SUBCUTANEOUS
      INFECTION WITH STAPHYLOCOCCI.
AB  - 1. On subcutaneous infection of rabbits with staphylococci of low virulence there
      appears at the place of injection first a hemorrhagicpurulent inflammation and
      later a localized purulence. In the regional lymph nodes there is lymphatic
      hyperplasia, and in the blood a lymphocytosis. 2. In the regional lymph nodes
      there is first a regressive change of Flemming's secondary nodules and of
      transition forms. Then follows lymphatic hyperplasia, starting apparently from
      solid secondary nodules and progressing by way of pseudo-secondary nodules to a
      diffuse lymphoid hyperplasia. The increase of lymphocytes in the blood parallels
      this development. 3. Only after the highest point of the lymphocytosis has been
      reached or passed do we find the first Flemming's secondary nodules, which
      thereafter increase in number and size while the number of lymphocytes in the
      blood falls, and reach their maximum development when the number of lymphocytes
      in the blood is again normal. Therefore, the original conception of Flemming that
      the site of formation of the lymphocytes of the blood is in Flemming's secondary
      nodules, cannot be accepted. 4. The lymphocytes of the blood originate in the
      pseudo-secondary nodules as in embryonic life. The mother cells of the
      lymphocytes would appear to be Marchand's proliferating endothelial (reticular)
      cells.

PMID- 19869552
TI  - STUDIES OF THE LYMPHATIC TISSUE : IV. EXPERIMENTAL STUDIES OF THE EFFECT OF THE
      INTRAVENOUS INJECTION OF KILLED STAPHYLOCOCCI ON THE BEHAVIOR OF LYMPHATIC
      TISSUE, THYMUS, AND THE VASCULAR CONNECTIVE TISSUE.
AB  - In 87 rabbits, some of which received intravenously at various intervals small,
      and some large, doses of killed staphylococci, the following findings were
      obtained. 1. There occurred a hyperplasia of lymph nodes, spleen and thymus, that
      is to say, a status thymicolymphaticus. This phenomenon is explained as due to
      immediate local irritation caused by bacteria and their products and by certain
      "toxins" partly of exogenous, partly of endogenous, origin. 2. The lymphocytosis
      which appeared was parallel in time and degree with the hyperplasia of the
      peripheral lymph nodes (axillary, popliteal and cervical lymph nodes) and
      probably originated in the pseudo-secondary nodules of these nodes. 3. There
      occurred intense mesenchymal reaction in the vascular connective tissue of the
      lungs, liver and spleen and after large doses slighter ones in adrenals, kidneys
      and heart. These reactions correspond with Oeller's adventitial reactions and
      Siegmund's intima proliferations. In the interstitial tissue of these organs as
      well as in the walls of the minor vessels proliferations of cells, partly of the
      type of lymphocytes and plasma cells, partly of that of histiocytes and reticulo
      endothelial cells, appeared, which, after large doses, were mixed with many giant
      cells of Langerhans' type. After small doses lymphocytes and plasma cells
      predominated, after large doses histiocytes and reticulo-endothelial cells.
      Because these reactions occurred immediately after the first injection, they can
      be regarded as primary reactions of the organism to bacteria and their products.

PMID- 19869553
TI  - THE DEVELOPMENT OF THE CHRONIC NEPHRITIS INDUCED IN THE DOG BY URANIUM NITRATE. A
      FUNCTIONAL AND PATHOLOGICAL STUDY WITH OBSERVATIONS ON THE FORMATION OF URINE BY
      THE ALTERED KIDNEYS.
AB  - 1. A chronic nephritis was produced in the dog which involves all of the
      histological elements of the kidney by the use of one subcutaneous injection of 4
      mg. of uranium nitrate per kilo. In such animals the sequence of the histological
      changes in the kidneys in correlation with their functional expression has been
      studied in dogs from the commencement of the; injury until the chronic nehritis
      has existed for 5 years and 2 months. 2. As early as the 2nd day following the
      development of an acute nephritis, the animals became polyuric with an albuminous
      urine containing granular casts. There was a marked reduction in the elimination
      of phenolsulphonephthalein, or it failed to appear in the urine in a 2 hour
      period. The reserve alkali of the blood was reduced to as low as 7.8 and a
      retention occurred in urea nitrogen, non-protein nitrogen and creatinine. At such
      periods of renal functional depression there was slight evidence of structural
      glomerular injury but marked evidence of proximal convoluted tubule degeneration
      and necrosis.

PMID- 19869554
TI  - THE FUNCTIONAL AND PATHOLOGICAL RESPONSE OF THE KIDNEY IN DOGS SUBJECTED TO A
      SECOND SUBCUTANEOUS INJECTION OF URANIUM NITRATE.
AB  - The present study permits the following conclusions. 1. Uranium nitrate in the
      dog has a high degree of selective affinity as a nephrotoxic for the epithelium
      of the proximal convoluted tubules. The glomeruli participate in the injury and
      develop obliterative connective tissue changes as evidence of a preexisting acute
      injury followed by repair. 2. The repair to the degenerated tubular epithelium is
      accomplished by two processes. First, by a regeneration of convoluted tubule
      cells from such cells not too severely injured in this location. This type of
      regenerated epithelium has no resistance to uranium. Second, the regeneration may
      occur as an ingrowth of cells or as syncytial buds from cells in the terminal
      portion of the proximal convoluted tubule or from the upper end of the descending
      limb of Henle's loop. This type of regenerated epithelium which is entirely
      different cytologically from normal convoluted tubule epithelium is resistant to
      a second injury from uranium even when the amount of this nephrotoxic agent has
      been increased to double the amount of the initial injection. 3. The kidney does
      not develop a local tissue immunity or resistance to uranium in the sense that
      cells of the same type once injured by it acquire as a result of the injury a
      resistance. The resistance and apparent but not real immunity is due to another
      type of cell with resistance having been substituted for a cell with but little
      resistance. This fact may be looked upon as constituting part of a defense
      mechanism in the kidney and may in part explain the long duration of certain
      types of chronic nephritic processes. 4. The functional studies which have been
      made during the initial injury from uranium to the tubules and during the
      secondary injury in animals which have either shown a resistance or a lack of
      resistance, emphasize the importance of the tubular epithelium as a part of a
      secretory mechanism in urine formation. During periods when the proximal
      convoluted tubule epithelium is in a state of acute degeneration there is a
      disturbance in the acid-base equilibrium of the blood, a reduction in the
      elimination of phenolsulphonephthalein and a retention of urea nitrogen, non
      protein nitrogen and creatinine. When this epithelium is regenerated by the
      formation of a tubular epithelium normal in character for this location of the
      tubule, regardless of structural changes in the glomeruli, the above evidence of
      renal dysfunction returns to the normal. If at such a period this type of
      regenerated epithelium be injured by a secondary injection of uranium a state of
      acute renal dysfunction is induced in an intensified form. In those animals in
      which the repair to the tubules was accomplished by the formation of an atypical
      type of epithelium in the convoluted tubules as well as by the formation of cells
      normal in histological appearance for this part of the tubule there was an
      improvement in the degree of depletion of the reserve alkali of the blood, in the
      elimination of phenolsulphonephthalein and in the retention of urea nitrogen, non
      protein nitrogen and creatinine. Certain of these values did not reach the
      normal. In such a state of renal repair when a second injection of uranium was
      given the kidney was found to have developed a marked resistance to it. There was
      but slight evidence of a depression in renal function. Associated with this
      acquired functional resistance there was no evidence of injury to the atypical,
      flattened regenerated epithelium of the proximal convoluted tubules.

PMID- 19869555
TI  - OUTLYING ACIDOSIS DUE TO FUNCTIONAL ISCHEMIA.
AB  - In various functional conditions involving peripheral vasoconstriction a more or
      less widespread change toward acidity takes place within certain tissues. The
      change is frequently independent of any in the blood. Indeed the blood can become
      more alkaline while the tissue acidosis is developing. When the blood volume is
      diminished abruptly but not too greatly, by hemorrhage or by anhydremia, the
      acidosis which develops in the superficial connective tissue and in the skeletal
      muscles is patchy in distribution, being limited to areas of local ischemia
      themselves the result of a compensatory vasoconstriction which affects certain
      regions only. There is a second type of patchy ischemia (and of acidosis) which
      occurs under circumstances of moderate depletion and is referable to local
      pressure differences that are so slight as to be ineffective under normal
      circumstances. A generalized acidosis throughout the superficial tissue develops
      when depletion is extreme. All these are outlying acidoses, since they lie
      without the influence of the blood. In the viscera no such acidoses have been
      found.

PMID- 19869556
TI  - THE SEPARATION OF TYPES AMONG THE PNEUMOCOCCI HITHERTO CALLED GROUP IV AND THE
      DEVELOPMENT OF THERAPEUTIC ANTISERUMS FOR THESE TYPES.
AB  - The pneumococci hitherto known as Group IV have been separated into ten types
      which have been designated by Roman numerals from IV to XIII. These have been
      correlated as far as possible with the types described by others. The prevalence
      and mortality of cases due to each type have been estimated in the limited number
      of cases studied. Laboratory tests indicated that therapeutic antiserums for
      Types I, II and III have very little protective power against the recently
      separated types. Monovalent antiserums of high agglutinative and protective power
      were prepared in rabbits for each type. Several monovalent antiserums each
      specific for a type, which are suitable for agglutination and experimental
      therapeutic use, have been obtained by immunizing horses. An antiserum prepared
      for one type had very little cross-protective power against other types.

PMID- 19869557
TI  - STUDIES ON BACTERIAL ENZYMES : VII. LACTASE AND LIPASE OF THE COLON BACILLUS.
AB  - Colon bacilli possess endocellular heat-labile lactase and lipase enzymes which
      remain operative in sterile filtered solutions of the intracellular substances
      obtained through physical disintegration the bacillary bodies. The demonstration
      of the lactase and detection of the hexose products of its action constitute
      experimental evidence that hydrolysis of the disaccharide is the first step in
      the fermentation of lactose by colon bacilli.

PMID- 19869558
TI  - THE NATURE OF THE HYPERGLYCEMIA ASSOCIATED WITH ANAPHYLACTIC SHOCK IN THE DOG.
AB  - 1. Nine unoperated dogs snowed a rise of blood sugar dunng anaphylactic shock. In
      six of these dogs the rise was 60 mg. or over. 2. Six dogs in which one adrenal
      had long previously been extirpated and the opposite splanchnic nerve cut, showed
      a low preliminary level of blood sugar, and a relative rise of blood sugar during
      anaphylaxis, but of less degree than in the unoperated animals. In no case was it
      greater than 52 mg. 3. Anoxemia did not appear to be a complicating factor, as
      evidenced by determination of the oxygen content of the arterial blood before and
      during shock. 4. The rise in blood sugar, which occurs in spite of the loss of
      adrenal activity, is probably due to the venous stasis of the liver seen in
      anaphylaxis in the dog, because this rise in blood sugar can be simulated in a
      normal non-sensitized dog by mechanically constricting the hepatic veins for a
      brief interval. 5. There are, therefore, probably two factors responsible for the
      hyperglycemia associated with anaphylaxis in the dog, sympathetic stimulation by
      way of the splanchnic nerves involving the activity of the adrenals, and
      glycogenolysis resulting directly from venous stasis of the liver.

PMID- 19869559
TI  - THE TOXICITY OF HUMAN SERUM FOR THE GUINEA PIG.
AB  - FROM THE FOREGOING STUDY THERE ARE INDICATIONS: 1. Of toxicity in all fresh human
      serum for the guinea pig; this toxicity tends to disappear after 48 hours after
      bleeding, and its manifestations are strikingly similar to those of the
      heterophilic antibody in immune rabbit serum. 2. Of an increased toxicity in the
      serum of antisera-treated human cases; this is usually coexistant with the
      production of other antibodies; it tends likewise to disappear in time after
      treatment; differential absorption experiments indicate that its character is
      heterophilic, and its manifestations differ from those of anaphylaxis in that
      certain circulatory effects-hemorrhage and increased edema in the lungs and
      distension of the right heart-are added to the usual findings in true
      anaphylactic deaths.

PMID- 19869560
TI  - OBSERVATIONS ON THE OXIDATION-REDUCTION PROPERTIES OF STERILE BACTERIOLOGICAL
      MEDIA.
AB  - Sterile plain broth contains an active oxidation-reduction system, the
      characteristics of which have been analyzed. 1. Intensity factor: Under vaseline
      seal, the lot of broth used in these experiments reaches a reduction potential
      corresponding to reduced indigo disulfonate (rH = 10). All the indicators with a
      more positive E(0)' are reduced, the others are not affected. It seems probable
      that fresh broth, which has not undergone oxidation by molecular oxygen, would
      give a higher reduction potential. 2. Capacity factor: The maximum amounts of
      different indicators that can be reduced correspond to equimolecular
      concentrations. This seems to indicate either (a) that the broth does not contain
      several "independent" reducing systems (at least in appreciable amounts), or (b)
      that these hypothetical "independent" systems all have about the same reduction
      potential. 3. Time factor: The different indicators of oxidation-reduction
      potentials are reduced in the order of the electromotive series. 4. Nature of the
      system: The system seems to be reversible (this not excluding the possibility of
      irreversible autoxidations) and does not appear to be of the nature of a sugar.
      The relation of these phenomena to the cultivation of different species of
      bacteria will be reported later.

PMID- 19869561
TI  - TREATMENT OF EXPERIMENTAL ACUTE GENERAL PERITONITIS IN THE DOG WITH ILEOSTOMY AND
      SODIUM CHLORIDE SOLUTION.
AB  - 1. In experimentally produced general peritonitis drainage of the gut by
      ileostomy 6 inches above the cecum has no beneficial effect. 2. Animals with
      experimentally produced general peritonitis treated with ileostomy plus 1 per
      cent sodium chloride solution live three times as long as those not given the
      salt solution.

PMID- 19869562
TI  - THE RAPID SHALLOW BREATHING RESULTING FROM PULMONARY CONGESTION AND EDEMA.
AB  - These experiments record the effects of the experimental production of pulmonary
      congestion and edema in a lung completely isolated from the general circulation,
      but with an intact nerve supply. The resulting changes are: a slowing of the
      heart rate, a fall in systemic blood pressure and a temporary inhibition of
      respiration succeeded by rapid shallow breathing. The pulse rate and blood
      pressure show a rapid and spontaneous return to initial conditions. The
      respirations show a partial but not a complete return to their former rate and
      depth. The effects on respiration are similar to those described by Dunn and
      Binger and Moore which follow multiple embolism of the pulmonary circuit with
      starch granules. The alterations in the pulse rate and blood pressure are
      characteristic of the effects of vagal stimulation. A chemical effect on the
      respiratory center is excluded by the nature of the preparation. These results,
      therefore, add further evidence to support the hypothesis that the rapid shallow
      breathing attending congestion and edema of the lungs is due to the stimulation
      of nerve endings in the lungs.

PMID- 19869563
TI  - NON-HEMOLYTIC STREPTOCOCCI AND ACUTE RHEUMATIC FEVER.
AB  - 1. Blood cultures from 25 cases of acute rheumatic fever were negative for non
      hemolytic streptococci of both the alpha and gamma types. 2. Non-hemolytic (gamma
      type) streptococci were frequently recovered from the throats of patients with
      this disease. 3. Similar organisms were recovered just as frequently from the
      throats of normal individuals. 4. Although these non-hemolytic streptococci were
      morphologically and culturally identical, not only amongst themselves, but also
      when compared with stock Small and Birkhaug strains, all, including the latter,
      have failed to show any noteworthy degree of homogeneity. 5. Representative
      strains of these streptococci have proved to be relatively non-pathogenic for
      rabbits following intravenous injection. 6. These organisms, with a few
      exceptions, have failed to produce soluble skin-reacting toxins comparable to
      Birkhaug's standard test toxin. 7. The foregoing facts seem to invalidate the
      assumption that any of these non-hemolytic streptococci play a specific role in
      the etiology of acute rheumatic fever.

PMID- 19869564
TI  - THE INITIATION OF GROWTH OF CERTAIN FACULTATIVE ANAEROBES AS RELATED TO OXIDATION
      REDUCTION PROCESSES IN THE MEDIUM.
AB  - The growth of many pathogenic organisms in plain meat infusion broth is possible
      only when a large inoculum is used. This requirement is much less strict when the
      broth cultures are incubated (a) under anaerobic conditions, (b) in fresh media
      very recently boiled or autoclaved, (c) in fresh media reduced by means of
      hydrogen, or to which small amounts of cysteine or of blood have been added. It
      is suggested that these findings can be accounted for by assuming that the
      bacterial species under consideration can multiply only in media the oxidation
      potential of which is below a critical value. The favorable growth conditions
      obtained by the procedures enumerated above may be attributed to the
      establishment of a proper reduction potential in the medium; the same result is
      obtained by using a large inoculum, owing to the reducing properties of bacterial
      cells.

PMID- 19869565
TI  - THE RELATION OF THE BACTERIOSTATIC ACTION OF CERTAIN DYES TO OXIDATION-REDUCTION
      PROCESSES.
AB  - Oxidized indophenols and methylene blue are bacteriostatic for Pneumococcus and
      hemolytic streptococci of human and bovine origin, while the indigoes, malachite
      green and litmus are not toxic. 2-Chloroindophenol, the most positive of the
      indicators of oxidation-reduction potentials used, is also the only one to have a
      bacteriostatic action on cheese strains of Streptococcus haemolyticus. Methylene
      blue and the indophenols are no longer bacteriostatic when present in a reduced
      form in a medium capable of maintaining them in such a condition. A comparison of
      these results with the growth in plain broth of the organisms studied suggests
      that the "inhibiting" dyes "poise" the medium at an oxidation potential outside
      the range in which the inhibited organisms can grow.

PMID- 19869566
TI  - STUDIES ON BACILLUS TYPHOSUS TOXIC SUBSTANCES : II. THE EFFECT OF SERA UPON THE
      FACTORS DETERMINING LOCAL SKIN REACTIVITY TO FILTRATES OF BACILLUS TYPHOSUS
      CULTURES.
AB  - It is shown in this paper that homologous immune sera are able to neutralize the
      B. typhosus skin-preparatory factors. The neutralization experiments were
      performed on a large number of rabbits, at least ten rabbits which showed
      positive control reactions being used for the titration of each serum. The
      rabbits into which the mixtures of B. typhosus culture filtrates with immune sera
      were injected can be divided into the following categories: those showing
      complete neutralization in highest dilutions (HN), those showing complete
      neutralization only in lower dilutions (LN) and those showing no neutralization
      (NN). The results indicate that the potency of a given serum as measured by the
      method outlined above has a direct relation to the reactions obtained in these
      groups of rabbits. For practical purposes the highest dilution of the serum which
      gives complete neutralization of the B. typhosus skin-preparatory factors (HN
      titer) may be taken as the actual titer of the serum as expressed in terms of
      their neutralization. The occurrence of a phenomenon suggestive of the prozone
      reaction is demonstrated. It also appears that the filtrates possess an
      antigenicity equal to that of dead and live bacteria. The studies on normal sera
      bring out the fact that normal sera fail to neutralize the B. typhosus skin
      preparatory factors unless agglutinins can be demonstrated for B. typhosus. No
      normal sera have thus far been obtained which neutralized the skin-preparatory
      factors yet contained no B. typhosus agglutinins, but there were sera which
      contained these agglutinins but failed to neutralize the skin-preparatory
      factors. Some of the normal animals whose sera failed to neutralize the skin
      preparatory factors were subsequently injected with B. typhosus culture filtrate
      and responded with neutralizing sera of high titer. Several heterologous sera
      were also investigated namely, scarlet fever, erysipelas, Shiga bacillus, Flexner
      bacillus, Mt. Desert bacillus, P. coli and B. avicida. These did not neutralize
      the B. typhosus skin-preparatory factors. Paratyphosus A and B sera on the other
      hand produced neutralization in various proportions. And the rabbits into which
      the serum-filtrate mixtures were injected could also be divided according to the
      results obtained into the same three groups as those with B. typhosus sera. It is
      not known yet whether this neutralization is a group reaction or whether the skin
      preparatory factors are identical with those of B. typhosus. It would appear from
      these studies that a method is available for the quantitative titration of
      substances in the serum which neutralize the skin-preparatory factors of local
      skin reactivity to B. typhosus culture filtrates. It should be emphasized that it
      is possible to control the individual susceptibility of rabbits to this
      phenomenon. The method should permit of considerable accuracy in the quantitative
      titration of the neutralizing properties of a serum when a standardized procedure
      is developed. Experiments are under way to determine whether the method can be
      applied to the preparation of therapeutic sera. Work is also in progress to
      determine the effect of specific antisera upon B. typhosus skin-reacting factors
      introduced by the intravenous route.

PMID- 19869567
TI  - BLOOD CHLORIDES IN CONDITIONS ASSOCIATED WITH PNEUMONIA.
AB  - Attempts have been made in dogs to lower the serum chlorides by means of various
      procedures. Of these the withholding of food, anoxemia, tissue destruction,
      anaphylactic shock, leucocytosis, and fever yielded negative results. Ingestion
      of large amounts of water lowered the chloride level independently of body
      temperature. The chloride drop under these circumstances could not be accounted
      for by excretion and appeared to run parallel with an increase in the serum water
      content. Experimental pneumococcus infection in two animals reduced the serum
      chloride concentration.

PMID- 19869568
TI  - REACTIONS OF RABBITS TO NON-HEMOLYTIC STREPTOCOCCI : I. GENERAL TUBERCULIN-LIKE
      HYPERSENSITIVENESS, ALLERGY, OR HYPERERGY FOLLOWING THE SECONDARY REACTION.
AB  - 1. Accompanying and following the evolution of a secondary reaction in the skin
      of rabbits after inoculation with suitable doses of certain non-hemolytic
      streptococci there quickly develops a general state of hypersensitiveness or
      allergy towards these streptococci. 2. This state is made evident by ophthalmic
      reactions following corneal inoculations, by much increased reactivity of the
      skin following intracutaneous reinoculations, and by lethal reactions, resembling
      tuberculin shock, following intravenous inoculations. 3. In a given
      hypersensitive rabbit there is a rough parallelism in the intensities of these
      different kinds of reactions. 4. This type of hypersensitiveness or bacterial
      allergy does not follow primary intravenous inoculation of rabbits with
      comparable doses of the streptococci employed. 5. As the development of this type
      of hypersensitiveness or bacterial allergy seems to accompany the production of
      focal lesions of a certain intensity, it is probable that in these foci are
      produced the substances or conditions which lead to this type of bacterial
      allergy.

PMID- 19869569
TI  - STUDIES ON INDIFFERENT STREPTOCOCCI : III. THE ALLERGIZING CAPACITY OF DIFFERENT
      STRAINS.
AB  - The indifferent streptococci are remarkably efficient allergizing agents when
      inoculated intradermally into rabbits. This is revealed by the high percentage of
      secondary reactions which occur in the lesions resulting from the inoculation of
      small doses of these organisms, and by the relative frequency with which positive
      ophthalmic reactions are obtained following sensitization with relatively small
      doses. This allergizing capacity is most marked in the organisms of Type I and
      least marked in the non-inulin-fermenting strains of Group X. The different
      resultants emerging from variations in allergizing capacity of streptococci and
      reactivity of host are clearly demonstrated in this series of experiments.

PMID- 19869570
TI  - TRANSMISSION OF FOWL-POX BY MOSQUITOES.
AB  - Culex and Aedes mosquitoes are capable of transmitting fowl-pox from diseased to
      healthy susceptible chickens. The mosquitoes remain infectious for at least 14
      days following a meal on diseased fowls.

PMID- 19869571
TI  - HERPES ENCEPHALITIS IN CEBUS MONKEYS.
AB  - Herpes virus which ordinarily produces in Cebus olivaceus monkeys an acutely
      fatal encephalitis closely resembling in time, symptoms and pathology the acute,
      herpetic disease of rabbits may-in more resistant individual monkeys-lead to a
      more prolonged malady which, while unquestionably produced with herpes virus,
      simulates with considerable accuracy the human disease of acute encephalitis, in
      symptoms, in course and in pathological changes.

PMID- 19869572
TI  - A STRAIN OF BACILLUS ABORTUS FROM SWINE.
AB  - The outbreak of infectious abortion in swine, probably the first reported from
      the eastern United States, was associated with a strain of Bacillus abortus
      growing rapidly on ordinary nutrient agar slopes without seal and presenting
      certain slight pathological deviations from the bovine form of disease in guinea
      pigs such as the occurrence of necrotic, suppurating foci in spleen and lymph
      nodes. Agglutination tests, comprising both cross-agglutination and absorption
      procedures failed to distinguish the strain from the bovine type. The gross
      appearance of the fetuses from this outbreak was normal. The shreds of placentas
      obtainable indicated slight erosion of the chorionic epithelium and some
      exudation. The specific bacilli were quite widely disseminated in the tissues of
      the fetuses. The pathogenic action of this swine strain on guinea pigs was
      evidently much feebler than that of most earlier swine strains as reported and it
      approached more closely that of bovine strains. The culture fed to a pregnant sow
      failed to produce abortion, possibly because of the advanced stage of pregnancy.
      The organism was not recovered from the uterus but was found in the sow's milk.

PMID- 19869573
TI  - THE REACTION OF HUMAN BILE AND ITS RELATION TO GALL STONE FORMATION.
AB  - 1. The human gall bladder acidifies the bile. In this respect its action is
      similar to that of the gall bladders of lower animals, previously described by
      other workers. 2. The hydrogen ion concentration of gall bladder bile is
      increased considerably in cases of obstruction of the common or cystic ducts. The
      highest values were found following complete obstruction. 3. The occurrence of
      gall stones was not associated with a consistent change in the hydrogen ion
      concentration of the gall bladder bile.

PMID- 19869574
TI  - DIFFERENTIATION BETWEEN SOME TOXIC SUBSTANCES IN ANAEROBICALLY PRODUCED
      AUTOLYSATES OF PNEUMOCOCCI (TYPES I AND II).
AB  - The necrotizing and lung-toxic principles present in certain anaerobically
      prepared autolysates of Pneumococcus Types I and II are similar in respect to
      extreme sensitiveness to heat and to oxidation, and to their ability to be
      neutralized by the same anti-autolysate serums. These two poisons differ,
      however, in their ability to be adsorbed or inactivated by red cells; the lung
      toxic principle being adsorbed or inactivated by such procedure while the
      necrotizing principle is not. Since pneumococcus hemotoxin is present in the
      anaerobic autolysates and is also adsorbed by red cells, it seemed possible that
      it was this substance in the autolysates which caused the diffuse lung lesions
      and death of guinea pigs. However, it was found that the intratracheal injection
      of pneumococcus hemotoxin prepared by the method of Avery and Neill only
      occasionally produced the characteristic reaction caused by the intratracheal
      injection of the anaerobic autolysates.

PMID- 19869576
TI  - BLOOD CALCIUM DISTRIBUTION IN ANAPHYLAXIS IN THE GUINEA PIG.
AB  - The results above reported for total calcium and the membrane-diffusible fraction
      in the serum of the guinea pig, taken at various intervals during anaphylactic
      shock, confirm the findings of previous workers that the total calcium is
      essentially unchanged. There is, however, the further finding that the diffusible
      fraction is considerably increased over that found for the animal similarly
      treated but not manifesting characteristic symptoms.

PMID- 19869575
TI  - SURVIVAL OF THE VIRUS OF POLIOMYELITIS FOR EIGHT YEARS IN GLYCEROL.
AB  - 1. An instance of successful inoculation of poliomyelitis virus after
      preservation for 8 years in 50 per cent glycerol is reported. 2. The virulence of
      the material injected remained essentially unchanged during this period. 3. The
      fact that poliomyelitis virus will survive in glycerol for so great a period may
      be taken as further indication of the improbability of streptococci as the
      inciting organisms. 4. Poliomyelitis virus would seem to vary in its resistance
      to glycerolation. 5. The remarkable persistence of active virus outside of the
      body may have a bearing on the epidemiology of poliomyelitis.

PMID- 19869577
TI  - OXIDATION-REDUCTION EQUILIBRIA IN BIOLOGICAL SYSTEMS : II. POTENTIALS OF AEROBIC
      CULTURES OF B. TYPHOSUS.
AB  - 1. The reduction potentials of B. typhosus in culture in bouillon which is given
      access to atmospheric oxygen show a negative drift that attains the values found
      in sterile bouillon when deaerated with nitrogen: Eh -0.085 to -0.095 volt at pH
      7.6. The potential reaches this level after 6 to 8 hours incubation, and is
      maintained at this point for several hours. A slow decline to more negative
      values is then observed and continues for at least 48 hours, when a potential of 
      0.145 volt may be attained. 2. The bacteria influence the potentials in the first
      period of their growth by exhaustion of oxygen from the culture, thus permitting
      the characteristic potential of the culture medium to become manifest, and do not
      contribute the substances responsible for the observed potentials. The decline in
      potential to values more negative than those of the culture medium occurs during
      the time that the rate of dying of the bacteria approaches and exceeds the rate
      of multiplication; it is suggested that dissolution of bacteria liberates
      reductive substances. 3. Cultures in 0.5 per cent dextrose medium show a somewhat
      more , negative potential after 18 hours growth than cultures in medium without
      dextrose. This may be due to the more rapid "turn-over" of the bacteria and the
      liberation of larger amounts of reductive material from dissolution of larger
      numbers of bacteria. 4. The potential of cultures through which oxygen is passed
      continuously does not show a negative drift at any time. This indicates that
      reductive substances of bacterial origin in the case at least of the typhoid
      bacillus do not influence the electrode potentials in the presence of oxygen and
      confirms the importance of bacterial respiration as the means for the removal of
      oxygen and the consequent establishment of characteristic reduction potentials in
      cultures.

PMID- 19869578
TI  - STUDIES ON THE PRECIPITABLE SUBSTANCES OF BACILLI OF THE SALMONELLA GROUP.
AB  - Specific precipitable substances rich in carbohydrates, containing very little
      protein and small amounts of a material apparently of fatty nature, have been
      prepared from the main serological types of the typhoid-paratyphoid groups. The
      preparations in their present state of purity do not exhibit very pronounced
      chemical differences in spite of serological dissimilarity. In this respect the
      results differ from those observed with the polysaccharides of pneumococci. The
      specificity of the precipitin reactions of these substances parallels in a
      general way the so called small flaking agglutination. Attempts to separate
      different fractions from the active substance serologically by means of
      precipitation with antibody solutions were on the whole unsuccessful. The
      differences in resistance to the action of acid and alkali were found to be
      characteristic for various specific carbohydrates.

PMID- 19869579
TI  - THE PRODUCTION OF PARTIAL LIVER INSUFFICIENCY IN RABBITS.
AB  - A rapid and simple method for the production of marked liver insufficiency in
      rabbits has been described. The necessary operation can be carried out by an
      unassisted operator in a few minutes. The method should further the study of
      liver physiology. The changes as concerns blood sugar, urea formation, and uric
      acid metabolism would appear to be the same in the rabbit suffering from hepatic
      insufficiency as in the dog.

PMID- 19869580
TI  - TOTAL SURGICAL REMOVAL OF THE LIVER IN RABBITS.
AB  - A technique is described for total removal of the liver of the rabbit without
      circulatory difficulties as a result. The method requires a preliminary operation
      to induce a development of portal and caval collaterals. Rabbits deprived of the
      liver in this manner if given glucose live for varying periods up to 40 hours.
      Before death they show the same disturbances as do hepatectomized dogs. They die
      early, of hypoglycemia, unless provided with sugar.

PMID- 19869581
TI  - THE RELATION OF THE LIVER TO FAT METABOLISM : I. EFFECT OF LIVER LACK ON FAT
      COMBUSTION AND THE RESPIRATORY QUOTIENT.
AB  - Fat combustion is carried on adequately in rabbits deprived of the liver or
      brought into a condition of extreme liver insufficiency. Even 24 hours after
      hepatectomy fat combustion goes on as well as in the normal animal. Evidently the
      liver plays no essential part in the breaking down of fat.

PMID- 19869582
TI  - ON THE MECHANISM OF OPSONIN AND BACTERIOTROPIN ACTION : I. CORRELATION BETWEEN
      CHANGES IN BACTERIAL SURFACE PROPERTIES AND IN PHAGOCYTOSIS CAUSED BY SERA OF
      ANIMALS UNDER IMMUNIZATION.
AB  - Methods are described for investigating the relation between phagocytosis of
      bacteria by polymorphonuclear leucocytes, and certain physical-chemical
      properties of the bacterial surface. Serum sensitization causes the following
      changes in the properties of acid-fast bacteria: (a) increased cohesiveness, (b)
      decrease in surface electric potential difference, (c) decrease in wettability of
      the bacteria by oil, and (d) increased phagocytosis. Tests have been conducted
      periodically with the sera of 4 rabbits under active immunization with as many
      strains of acid-fast bacteria; the parallelism between the alteration in
      bacterial surface properties and the promotion of phagocytosis by these sera has
      been, within the experimental error, complete. The percentage of phagocytosis of
      a given bacterial suspension has been found to depend both upon the sensitizing
      serum component or components deposited upon the bacterium and upon the intrinsic
      properties of the unsensitized bacterial surface.

PMID- 19869583
TI  - ON THE MECHANISM OF OPSONIN AND BACTERIOTROPIN ACTION : II. CORRELATION BETWEEN
      CHANGES IN BACTERIAL SURFACE PROPERTIES AND IN PHAGOCYTOSIS CAUSED BY NORMAL AND
      IMMUNE SERA.
AB  - The work reported in this and in previous papers (1, 7) demonstrates the
      following relations for acid-fast bacteria and rabbit polymorphonudear
      leucocytes: 1. The combination of a substance or substances present in fresh
      immune rabbit serum, heated or unheated, or in fresh unheated normal rabbit
      serum, with a substance or substances in the bacterial surface causes an increase
      in cohesiveness, decrease in surface potential difference and characteristic
      alteration in wetting properties of the bacteria, and prepares the bacteria for
      phagocytosis. 2. (a) The effective substance or substances in the serum may
      become so altered as the result of heating or aging that combination with the
      bacterial surface, while causing changes in bacterial surface properties
      indistinguishable by the present physical-chemical tests from these just
      mentioned, may not lead to phagocytosis, or may lead to phagocytosis with a
      prezone not paralleled by a prezone in the changes in surface properties. (b)
      Sensitization of bacteria with human sera causes changes in surface properties
      similar to those caused by rabbit sera, but does not lead to phagocytosis by
      rabbit leucocytes. The spreading requirements of rabbit polymorphonuclear
      leucocytes are evidently highly selective.

PMID- 19869584
TI  - ON THE MECHANISM OF OPSONIN AND BACTERIOTROPIN ACTION : III. THE DEVELOPMENT AND
      EFFECT OF THE ANTIBODIES FOUND IN EXPERIMENTAL TUBERCULOSIS OF RABBITS.
AB  - Rabbits infected intravenously with virulent mammalian tubercle bacilli have in a
      majority of cases developed circulating antibodies to a slight but appreciable
      degree. The increase in titer was detected in one group of rabbits within the 2nd
      or 3rd week, in others during the 2nd month of infection. Rabbits with residual
      pulmonary foci, resulting from infection 6 months or more previously with human
      tubercle bacilli, on reinfection with bovine tubercle bacilli promptly developed
      circulating antibodies strikingly in excess of those found during the course of
      primary infection. Such antibodies were present 6 or 7 days after reinfection.
      The changes in titer during tuberculous infection as detected by the bacterial
      surface reactions and by phagocytosis were again, within the experimental error,
      in quantitative correspondence. The loss of phagocytosis-promoting power in
      heated normal serum involves an exception to this correspondence between surface
      and phagocytosis effects. This exception has already been discussed in an earlier
      paper (8).

PMID- 19869585
TI  - TRANSMISSION OF RESPIRATORY ANAPHYLAXIS (ASTHMA) FROM MOTHER TO OFFSPRING.
AB  - Rabbits immunized intravenously with living culture or nucleoproteins of non
      hemolytic streptococci react to subsequent intracutaneous inoculations with
      homologous streptococci with smaller and harder lesions than are shown by normal
      animals similarly inoculated; and they do not develop the general manifestations
      of hypersensitiveness such as are shown by animals previously inoculated into the
      tissues with the same cultures. A rabbit may react to intracutaneous inoculation
      with non-hemolytic streptococci in one of four ways, depending on whether it is
      normal, hypersensitive, immune or cachectic. Most normal animals show a secondary
      reaction about 10 days after inoculation with suitable strains of non-hemolytic
      streptococci; hypersensitive, allergic, or hyperergic animals show much larger
      lesions than do normals with the corresponding doses of the same streptococci,
      and practically never show secondary reactions; immune animals show smaller and
      harder early lesions and usually do not have secondary reactions if they are
      fairly well immunized. Cachectic animals show very soft and rapidly fading
      primary reactions and no secondary reactions.

PMID- 19869586
TI  - A "SOLUBLE SPECIFIC SUBSTANCE" DERIVED FROM GUM ARABIC.
AB  - 1. By partial acid hydrolysis a specific carbohydrate may be isolated from gum
      arabic (gum acacia). This carbohydrate is comparable in its precipitating
      activity for Type II (and Type III) antipneumococcus serum with the bacterial
      soluble specific substances themselves. 2. On hydrolysis this fraction yields
      galactose and two or more complex sugar acids, one of which appears to be a
      disaccharide add comparable with those isolated from the specific polysaccharides
      of the Type III pneumococcus and the Type A Friedlander bacillus. 3. The
      significance of these findings is discussed.

PMID- 19869587
TI  - BIOMETRY OF CALCIUM, INORGANIC PHOSPHORUS, CHOLESTEROL, AND LIPOID PHOSPHORUS IN
      THE BLOOD OF RABBITS : III. INFLUENCE OF VARIOUS TYPES OF LIGHT ENVIRONMENT.
AB  - Experiments are reported in which it was shown that the calcium, inorganic
      phosphorus, cholesterol, and lecithin in the blood of normal rabbits were
      influenced by 4 types of light environment. The results of the experiments seem
      to warrant the following conclusions: 1. Animals exposed to the ultra-violet
      light for a brief period each day give results which are diametrical to those
      obtained for animals living in total darkness. 2. The results obtained for
      animals exposed to the Cooper Hewitt light and for those living in the open
      laboratory are somewhat similar but occupy a position between those of the dark
      and ultra-violet groups. 3. Animals do not develop immediately the characteristic
      effects of a particular environmental condition, but pass through a period of
      accommodation which varies somewhat with different environmental conditions.

PMID- 19869588
TI  - REACTIONS OF RABBITS TO NON-HEMOLYTIC STREPTOCOCCI : II. SKIN REACTIONS IN
      INTRAVENOUSLY IMMUNIZED ANIMALS.
AB  - Rabbits immunized intravenously with living culture or nucleoproteins of non
      hemolytic streptococci react to subsequent intracutaneous inoculations with
      homologous streptococci with smaller and harder lesions than are shown by normal
      animals similarly inoculated; and they do not develop the general manifestations
      of hypersensitiveness such as are shown by animals previously inoculated into the
      tissues with the same cultures. A rabbit may react to intracutaneous inoculation
      with non-hemolytic streptococci in one of four ways, depending on whether it is
      normal, hypersensitive, immune or cachectic. Most normal animals show a secondary
      reaction about 10 days after inoculation with suitable strains of non-hemolytic
      streptococci; hypersensitive, allergic, or hyperergic animals show much larger
      lesions than do normals with the corresponding doses of the same streptococci,
      and practically never show secondary reactions; immune animals show smaller and
      harder early lesions and usually do not have secondary reactions if they are
      fairly well immunized. Cachectic animals show very soft and rapidly fading
      primary reactions and no secondary reactions.

PMID- 19869589
TI  - RELATION OF VARICELLA TO HERPES ZOSTER : I. STATISTICAL OBSERVATIONS.
AB  - Varicella most frequently occurs in individuals under 10 years of age, while
      zoster as a rule is observed in persons beyond that age. The number of cases of
      varicella exhibits a markedly constant seasonal variation. The variations in the
      prevalence of herpes zoster are not regular and do not parallel those of
      varicella.

PMID- 19869590
TI  - RELATION OF VARICELLA TO HERPES ZOSTER : II. CLINICAL AND EXPERIMENTAL
      OBSERVATIONS.
AB  - Experiments and clinical observations dealing with the identity of the viruses of
      varicella and herpes zoster were presented. The results indicate that the
      etiological agents concerned with these two diseases are in the majority of
      instances not identical.

PMID- 19869591
TI  - IMMUNOLOGIC REACTIONS WITH TOBACCO MOSAIC VIRUS.
AB  - 1. Antisera were produced, separately, in rabbits to normal sap from healthy
      Turkish tobacco plants and to irus-sap from tobacco plants, affected with mosaic
      disease. 2. The immunologic reactions of the antisera were studied by means of:
      (a) Alexin-fixation tests. (b) Precipitation experiments, including: Precipitin
      absorption tests with the same tobacco virus multiplied in tobacco, tomato,
      pepper, and petunia plants. (c) Experiments with the inactivation properties of
      both antisera and normal serum on virus-sap. 3. From the results obtained from
      the above experiments, the following conclusions were drawn: (a) Normal-tobacco
      sap and virus-tobacco-sap possess antigenic substances in common. (b) Normal sap
      and virus-sap of tomato, pepper, and petunia plants contain antigenic substances
      in common with normal sap of tobacco. (c) Virus-saps of tomato, pepper, and
      petunia plants, have antigenic substances in common with virus-sap of tobacco,
      that are either not present in the normal tobacco sap or present only in small
      amounts. (d) The two antisera possess alexin-fixing antibodies and precipitins in
      common. (e) All of the precipitins to normal tobacco sap may be removed from
      either antiserum by absorption with virus-sap of tobacco. (f) Specific
      precipitins for virus-sap of tobacco, tomato, pepper, and petunia are present in
      the antiserum to tobacco virus-sap and cannot be removed by complete absorption
      with normal sap of tobacco. (g) Antiserum to virus-sap of tobacco, when used in
      an appropriate amount, has the power of completely inactivating virus-sap. A
      corresponding quantity of antiserum to normal tobacco sap, or normal rabbit or
      guinea-pig serum, does not exhibit the same preventive action on virus-sap. (h)
      There is some evidence that a specific antibody to virus-sap, lytic in nature, is
      present in the homologous antiserum.

PMID- 19869592
TI  - THE RELATION OF CHROMATIN TO HEMOGLOBIN AND BILIRUBIN.
AB  - 1. Attention is directed to the diversity of opinion among investigators
      regarding the site and manner of hemoglobin formation in the body and its
      relation to bile pigment metabolism. 2. It is probable that in forming new
      hypotheses on this subject the earlier work of A. B. Macallum on the relation of
      chromatin to hemoglobin formation has not received sufficient consideration. 3.
      It has been shown by means of microchemical iron stains of the bone marrow cells,
      that the iron content of the hematoblast is increased during rapid hemoglobin
      production in simple anemia. 4. This fact is compatible with the work of Macallum
      who believed that hemoglobin is derived from the chromatin of the hematoblast. It
      does not support a theory that hemoglobin is formed as a part of a circulating
      pigment. 5. It is suggested that bilirubin is derived from the chromatin of body
      cells through the intermediary stages of the respiratory pigments, hemoglobin and
      cytochrome, from erythrocytes and other cells, respectively.

PMID- 19869593
TI  - EXPERIMENTAL DEHYDRATION: CHEMICAL CHANGES IN THE BLOOD OF THE DOG CONTRASTED
      WITH THOSE FOLLOWING OBSTRUCTION OF THE CARDIAC END OF THE STOMACH.
AB  - A comparative chemical study of the blood and the urine of the dog with
      experimental dehydration and with obstruction of the cardiac end of the stomach
      is reported. The average duration of life is slightly longer with dehydration
      than with obstruction. The urine output per kilo of body weight is almost twice
      as great in dehydration as with obstruction. The increase in non-protein nitrogen
      and urea nitrogen is much the same in the two groups although somewhat more
      marked with obstruction. The chlorides of the blood are markedly increased with
      dehydration and slightly decreased with obstruction. The increase in fibrinogen
      and total protein is twice as great with obstruction as with dehydration. These
      findings indicate that there must be some factor or factors in addition to
      dehydration producing the toxemia of cardiac obstruction.

PMID- 19869594
TI  - CHEMICAL FINDINGS IN THE BLOOD OF THE DOG AFTER CLOSED-LOOP OBSTRUCTION OF THE
      JEJUNUM.
AB  - The chemical findings in the blood of 6 dogs with closed-loop obstruction of the
      upper jejunum are reported. The duration of life with closed loops is less than
      with simple obstruction. All animals showed a marked rise in non-protein nitrogen
      and urea nitrogen, and fall in chlorides. Usually the C0(2) combining power of
      the plasma is increased. The findings in closed-loop obstruction are essentially
      the same as in simple intestinal obstruction.

PMID- 19869595
TI  - INTRADERMAL VERSUS SUBCUTANEOUS IMMUNIZATION OF MONKEYS AGAINST POLIOMYELITIS.
AB  - 1. The introduction of considerable amounts of living, active poliomyelitis virus
      into the skin and subcutaneous tissue of monkeys protects the animals against
      intracerebral inoculations of similar virus material. 2. The degree of protection
      conferred by intradermal is greater than by subcutaneous injection. 3. During
      intradermal and subcutaneous inoculations, no local or general pathological signs
      were observed. 4. The degree of protection produced by the immunization methods
      used is not absolute, since a percentage of the inoculated monkeys respond to
      intracerebral injections of highly potent virus. 5. The sera of the animals
      inoculated intradermally or subcutaneously neutralized poliomyelitis virus in
      vitro, irrespective of the result of intracerebral inoculation, in all except one
      instance. 6. The power of the serum of treated monkeys to neutralize virus in
      vitro is a more delicate test of immunity than is the intracerebral inoculation.

PMID- 19869596
TI  - STUDIES ON SOUTH AMERICAN YELLOW FEVER : I. THE STRAINS OF VIRUS IN USE AT THE
      YELLOW FEVER LABORATORY IN BAHIA, BRAZIL.
AB  - It would appear that inoculation of rhesus monkeys served a diagnostic purpose in
      one of our cases, that of S. R. The disease was so mild that in the absence of an
      epidemic no clinician would have made the diagnosis without this laboratory
      procedure. It should be pointed out that following inoculation of liver emulsion,
      and sometimes even of blood, it is impossible to tell whether an early fever
      resulting is due to a protein reaction, to bacterial infection, or to true yellow
      fever. If plenty of animals are available the only safe plan is to take blood for
      subinoculation and for cultures, and to feed mosquitoes. Blood may be kept frozen
      for some time before inoculation if it is found to be necessary, or if it is
      desired to await the outcome of the disease in the animal bled. A combined blood
      and liver transfer showed the presence of virus in rhesus No. 46 twenty days
      after the original inoculation with kidney from the autopsy in the case of J. V.
      0. The same animal had had an infected body wall and a bacteriemia. On the basis
      of later experience we can see some of our mistakes. In the second S. R. passage
      (rhesus No. 133) blood transfer should have been made at the time of initial
      fever, the day following inoculation. In the case of rhesus No. 60, mosquito
      infection from J. V. 0., transfer probably should have been made when the
      temperature reached 103.9 degrees F. on the fifth day. Two days later, with a
      fever of 104.4 degrees F., the blood appeared to be non-infective. A temperature
      of 104 degrees F. in monkeys is usually a safe borderline between fever and no
      fever, but seemingly not always. Our experience with the South American viruses
      so far indicates that it takes much care, patience, and an abundance of monkeys
      to build up and maintain a high degree of virulence.

PMID- 19869597
TI  - STUDIES ON SOUTH AMERICAN YELLOW FEVER : II. IMMUNITY OF RECOVERED MONKEYS TO
      AFRICAN VIRUS.
AB  - These experiments indicate that, although there are quantitative differences in
      virulence and minor differences in behavior, the African strain and the Brazilian
      strains of yellow fever virus tested are immunologically the same.

PMID- 19869598
TI  - ETIOLOGY OF OROYA FEVER : XIV. THE INSECT VECTORS OF CARRION'S DISEASE.
AB  - With a view to determining the mode of infection in Carrion's disease, a study of
      the blood-sucking insects found in the districts of Peru where the disease
      prevails has been carried out, through the cooperation of The Rockefeller
      Institute and the Rockefeller Foundation. The material studied included ticks,
      mites, midges, lice, fleas, bedbugs, mosquitoes, buffalo gnats, horse-flies,
      "sheep ticks," 3 species of Streblidae, and 3 species of Phlebotomus, including
      Phlebotomus verrucarum Townsend and two new species which have been named
      Phlebotomus noguchii and Phlebotomus peruensis. The insects were collected
      without the use of chemicals, were prepared for transportation in such a manner
      as to prevent drying, and were shipped under conditions of refrigeration to New
      York, where they were inoculated into monkeys. The plan followed was to inject
      saline suspensions of the crushed insects intradermally into rhesus monkeys and
      to make cultures of the blood of the animals at intervals of 1 to 6 weeks after
      inoculation. The only class of insects in which the presence of Bartonella
      bacilliformis could be detected were phlebotomi. No cutaneous lesions were
      induced in monkeys injected with the crushed insects, but in the case of four
      different lots of phlebotomi the blood of the animals so injected yielded
      cultures of Bartonella bacilliformis which produced typical verrucous lesions on
      inoculation into other monkeys. The morphology and cultural characteristics of
      the Bartonella strains obtained from phlebotomi proved identical with those of
      strains isolated from human blood and skin lesions. Monkeys which had recovered
      from infection with the phlebotomus strains resisted inoculation with a human
      strain of Bartonella bacilliformis, and, conversely, monkeys which had passed
      through an infection induced by the human strain resisted inoculation with the
      strains obtained from phlebotomi. The experimental observations described in this
      paper lead us to conclude that certain phlebotomi act as insect vectors of Oroya
      fever and verruga peruana. The phlebotomi which have been shown quite certainly
      to carry the Bartonella bacilliformis are those of the species Phlebotomus
      noguchii. Phlebotomus verrucarum is also probably a vector, while Phlebotomus
      peruensis remains doubtful in this respect.

PMID- 19869599
TI  - THE PRESERVATION OF YELLOW FEVER VIRUS.
AB  - 1. The virus of yellow fever may be preserved for at least 154 days in the blood
      or liver tissue of infected monkeys if the material is dried in a vacuum while in
      the frozen state and kept in the refrigator in sealed glass containers. A gradual
      diminution of virulence is noticeable in the older specimens. 2. If infectious
      blood is dried in a vacuum at room temperature, instead of in the frozen state,
      and is stored in sealed containers in the refrigerator, the virus may survive as
      long as 155 days. 3. The virus may be preserved for at least 30 days in liver
      kept continuously frozen. 4. Storage of blood or liver in 50 per cent glycerine
      in the refrigerator will usually keep the virus alive for 60 days and may do so
      for 100 days, but with the injection of the older material there is a marked
      tendency toward lengthening of the incubation period and increase in the number
      of recoveries. 5. Yellow fever virus in citrated or clotted blood, when kept in
      the refrigerator, dies out rapidly. 6. In our experience the most satisfactory
      method of preserving strains of yellow fever virus in the laboratory consists of
      freezing and drying blood taken from a monkey on the first day of an attack of
      experimental yellow fever and storing the dry material in sealed glass tubes in a
      cold place.

PMID- 19869600
TI  - THE PRODUCTION AND TITRATION OF POTENT HORSE ANTIPNEUMOTOXIN.
AB  - 1. The serum of horses immunized with increasing doses of certain anaerobically
      produced autolysates of pneumococci contain potent neutralizing antibodies for
      the pneumotoxin. 2. The method for the in vitro titration of these horse
      antipneumotoxic serums is given.

PMID- 19869601
TI  - BIOMETRY OF CALCIUM, INORGANIC PHOSPHORUS, CHOLESTEROL, AND LECITHIN IN THE BLOOD
      OF RABBITS : IV. EFFECTS OF A MALIGNANT TUMOR.
AB  - Experiments are reported in which it was shown that the calcium, inorganic
      phosphorus, cholesterol, and lecithin in the blood of normal rabbits were
      influenced by inoculation with a malignant tumor (4). Animals in which death was
      due to tumor gave results on which the following conclusions are based: 1. A
      marked increase in inorganic phosphorus of blood serum and cholesterol of whole
      blood followed inoculation. 2. The ratios of cholesterol to calcium and lecithin
      to calcium increased in trend, while the calcium to inorganic phosphorus,
      lecithin to cholesterol, and lecithin to inorganic phosphorus ratios showed a
      marked decrease in trend. 3. The r cholesterol-lecithin were all negative.

PMID- 19869602
TI  - BLOOD AND BONE MARROW CELLS OF THE DOMESTIC FOWL.
AB  - 1. A simple, direct method of counting leucocytes of the fowl is described. 2.
      Twenty-nine complete, morphological studies of the blood of eleven domestic fowls
      are recorded. 3. The characteristics of the cells found in the blood and bone
      marrow are described in detail and their relative numbers reported. 4. The
      supravital technique, using neutral red and Janus green, enables one to separate
      and classify accurately the confusing cells of the blood and bone marrow. 5.
      These studies provide a basis for future experimental studies on the blood and
      bone marrow cells of the fowl.

PMID- 19869603
TI  - A COMPARISON OF THE MANNER OF EXCRETION OF NEUTRAL RED AND PHENOL RED BY THE
      FROG'S KIDNEY.
AB  - 1. Phenol red and neutral red are excreted by the perfused frog's kidney by
      different routes. 2. Phenol red is excreted chiefly through the glomerulus,
      neutral red through the tubules. 3. Some slight excretion of each of these dyes
      by the converse mechanism is possible, though there is no evidence in our
      experiments that necessitates such a conclusion. 4. The importance of methods
      leading to the production of a normal volume of urine by the perfused kidney is
      emphasized.

PMID- 19869604
TI  - FURTHER NOTES ON THE FILTRATION OF THE VIRUS OF VACCINIA.
AB  - 1. A very active filtrate can be obtained from vaccinia lesions by grinding up
      the fresh tissue with glass fragments, emulsifying in hormone broth, centrifuging
      the emulsion and filtering the supernatant fluid through a Berkefeld V filter. 2.
      The sterile filtrate so obtained has been shown by comparative titration on
      rabbits to have about one-sixteenth of the activity of the non-sterile emulsion
      used in human vaccination. 3. Centrifugation of such a filtrate shows a partial
      concentration of the virus in the lowermost layer. 4. The virus survives for a
      long time, if the filtrate is kept near the freezing point, and probably will
      survive indefinitely if kept frozen. The addition of glycerine is not necessary.

PMID- 19869605
TI  - ATTEMPTS TO REPRODUCE RHEUMATIC FEVER IN ANIMALS.
AB  - Experiments have been described in which we attempted to reproduce in animals the
      lesions characteristic of rheumatic fever in the human. A large number of animals
      representing 7 species was employed. Among other materials, streptococci isolated
      in pure culture from the blood of rheumatic patients (proved to be so by biopsy
      or by autopsy) as well as whole blood, plasma, serum, pericardial, pleural and
      hydrocele fluid, filtrates from tonsils, subcutaneous nodules, lymph nodes, and
      nasopharyngeal washings obtained from such patients were used in a variety of
      combinations and with a number of procedures calculated to predispose the animal
      to the disease. A discussion is given of the criteria whose fulfillment is
      essential for the establishment of the experimental production of rheumatic
      disease in animals. Judged by these criteria, we have failed to reproduce the
      disease. This conclusion, we believe, holds true for all the work thus far
      reported in the literature.

PMID- 19869606
TI  - ON THE RELATION OF BACTERIA TO SO-CALLED "CHEMICAL PNEUMONIA".
AB  - The question of a causal relation of the bacteria in gassed lungs to the
      pneumonia present cannot be regarded as decided. It may be said that: 1. The
      appearance of gassed lungs with pneumonia is very similar to the pneumonia of
      known bacterial origin. 2. In a few cases the type of pneumonia found coincides
      with the reported cases of so-called "chemical pneumonia," which is characterized
      by a preponderance of epithelial cells in the exudate. 3. Gassed lungs are not
      sterile but show highly varying numbers of bacteria. 4. The bacteria are not
      intracellular and are not present in large numbers in the majority of cases. The
      arguments for and against a causal relationship between the bacteria and the
      pneumonia may be summed up as follows: 1. Against a Causal Relationshipa. The
      early appearance of pneumonia after gassing. b. The occurrence of pneumonia with
      very small numbers of bacteria present. c. The fact that very few bacteria are
      engulfed by leucocytes in gassed lungs, whereas large numbers are present in the
      non-gassed pneumonias and are conspicuously intracellular. 2. In Favor of a
      Causal Relationshipa. The presence of bacteria in any numbers. b. The picture of
      broncho-pneumonia presented is similar to broncho-pneumonia of known bacterial
      origin. c. Pneumonias characterized by large numbers of epithelial cells in the
      exudate (so-called "chemical pneumonia") occur in animals that were never gassed
      or subjected to other irritating substances in any way.

PMID- 19869607
TI  - STUDIES ON SOUTH AMERICAN YELLOW FEVER : III. TRANSMISSION OF THE VIRUS TO
      BRAZILIAN MONKEYS PRELIMINARY OBSERVATIONS.
AB  - Yellow fever virus from M. rhesus has been inoculated into a South American
      monkey (Cebus macrocephalus) by blood injection and by bites of infected
      mosquitoes. The Cebus does not develop the clinical or pathological signs of
      yellow fever. Nevertheless, the virus persists in the Cebus for a time as shown
      by the typical symptoms and lesions which develop when the susceptible M. rhesus
      is inoculated from a Cebus by direct transfer of blood or by mosquito (A.
      aegypti) transmission.

PMID- 19869608
TI  - IMMUNOLOGICAL STUDIES IN RELATION TO THE SUPRARENAL GLAND : IV. THE EFFECT OF
      REPEATED INJECTIONS OF EPINEPHRINE ON THE HEMOLYSIN FORMATION IN
      SUPRASENALECTOMIZED RATS.
AB  - Epinephrine diluted with physiological salt solution or with isotonic glucose
      solutions and injected in amounts of 0.2 mg. per kilo twice daily into
      suprarenalectomized rats raises their antibody forming capacity. This result is
      not entirely dependent on the effect of the diluting fluid.

PMID- 19869609
TI  - IMMUNOLOGICAL STUDIES IN RELATION TO THE SUPRARENAL GLAND : V. THE EFFECT OF
      REPEATED INJECTIONS OF SOLUTIONS CONTAINING SODIUM SALTS AND GLUCOSE ON THE
      HEMOLYSIN FORMATION OF NORMAL AND SUPRARENALECTOMIZED RATS.
AB  - Table I and Figs. 1 and 2 summarize the experiments done on 150 rats.
      Suprarenalectomy in rats is followed by a striking depression in antibody
      formation most marked during the first week following the operation. Repeated
      injections of large amounts of isotonic sodium chloride or sodium acetate
      solutions restore the antibody titer to normal. The effect of these solutions is
      not due to diuresis alone, since isotonic glucose solution does not affect the
      titer, nor to the sodium alone, since hypertonic solutions of sodium chloride in
      small volume have little influence on the titer. Both the sodium ion and the
      water volume are necessary in the restoration of the titer.

PMID- 19869610
TI  - THE ROLE OF CARBOHYDRATES IN BIOLOGICAL OXIDATIONS AND REDUCTIONS. EXPERIMENTS
      WITH PNEUMOCOCCUS.
AB  - The reducing power of plain broth cultures of Pneumococcus is largely dependent
      upon the presence in the medium at the time when the reduction test is performed
      of certain metabolites. The washed cells of Pneumococcus are able to reduce the
      various indicators of oxidation-reduction potentials in the presence of glucose.
      The relative velocity of reduction of these indicators is determined by the
      number of cells used in the test, the concentration of the dyes, and their
      position in the oxidation reduction scale. Oxidized thiol compounds (glutathione,
      cystine, oxidized thioglycollic acid) are likewise rapidly reduced by glucose in
      the presence of washed cells of Pneumococcus. This Pneumococcus-glucose system is
      able to form peroxide under aerobic conditions. Those substances which form
      peroxide in the presence of Pneumococcus cells are also the ones which Cole found
      to be active in changing hemoglobin into methemoglobin under the same conditions.
      The power of washed cells of Pneumococcus to reduce methylene blue in the
      presence of glucose is dependent on at least 2 constituents: one which can be
      readily removed from the cell by washing. Sugar-free meat infusion will function
      instead of it. The other is inactivated more slowly by the process of washing and
      is destroyed by 10 minutes heating at 55 degrees C. The interreaction between the
      glucose and the cell seems to result in a fundamental reaction in which one
      molecule of glucose becomes able to reduce rapidly one molecule of methylene
      blue. The existence of side-reactions often obscures this ratio. The significance
      of these observations is considered in relation to the nature and mechanism of
      the "activation" of metabolites, the preparation of synthetic media, the
      phenomena of growth, and the meaning of the expression "reducing power of a
      bacterial culture."

PMID- 19869611
TI  - EXPERIMENTAL PNEUMONIA IN GUINEA PIGS : II. EFFECT OF ANTI-AUTOLYSATE SERA ON
      PNEUMOCOCCUS PNEUMONIA IN GUINEA PIGS.
AB  - 1. Anti-pneumotoxic sera prepared in rabbits or horses by immunization with
      sterile filtrates of the pneumotoxin, under certain conditions protect against
      the pneumonia caused by the intratracheal injections of mixtures of living
      pneumococci and toxic autolysates. 2. The protection against the development of
      pneumonia is heterologous, at least as regards Type I, Type II, viz.: an anti
      autolysate serum prepared by the immunization with a pneumotoxin from one type of
      pneumococcus will prevent the development of pneumonia caused by the injection of
      pneumococci and autolysate from another type. 3. Certain anti-pneumococcus horse
      sera used in the treatment of pneumonia in man, either contain no heterologous
      pneumonia-preventing antibodies or slight amounts only. These sera, however,
      protect against the pneumonia produced by injections of pneumococci and
      pneumotoxin of the homologous strain, the degree of protection depending on the
      amount of specific protective substances such sera contain. 4. Anti-pneumotoxic
      sera produced in rabbits or horses by the injection of sterile Berkefeld
      filtrates of the toxic autolysates contain no pneumococcus specific protective
      substances.

PMID- 19869612
TI  - STUDIES ON INFLAMMATION : I. FIXATION OF VITAL DYES IN INFLAMED AREAS.
AB  - Trypan blue injected into normal subcutaneous tissue passes rapidly to the
      regional lymphatic node and is found in lymph drawn from its efferent lymphatic.
      When the dye is injected into the normal peritoneal cavity it rapidly appears in
      the lymph of the retrosternal lymphatics and stains deeply the retrosternal
      lymphatic nodes. Trypan blue injected into the site of inflammation in the
      subcutaneous tissue or in the peritoneal cavity is fixed in the inflamed area and
      fails to reach the regional lymphatic nodes. If an inflammatory reaction has been
      produced in the dermis or in the subcutaneous tissue, trypan blue injected into
      the circulating blood enters the site of inflammation and is fixed so that the
      tissues are deeply stained.

PMID- 19869613
TI  - OBSERVATIONS CONCERNING THE PERSISTENCE OF LIVING CELLS IN MAITLAND'S MEDIUM FOR
      THE CULTIVATION OF VACCINE VIRUS.
AB  - Cells survive for at least 5 days and at times are capable of multiplying in a
      mixture of serum and Tyrode's solution used by Maitland for the cultivation in
      vitro of vaccine virus.

PMID- 19869614
TI  - STUDIES OF TISSUE MAINTENANCE : I. THE CHANGES WITH DIMINISHED BLOOD BULK.
AB  - The spread through the living animal of various highly diffusible dyes has been
      utilized as an indicator of the ability of the circulation to serve the tissues
      under various conditions. The method is direct and searching. Blood service to
      the viscera, as demonstrated by it, is normally far more profuse than to the skin
      and muscles, for evident physiological reasons. After hemorrhages which greatly
      reduce the blood bulk service to the viscera is in general still well maintained
      even though the animal be in extremis. However great the compensatory contraction
      of the splanchnic vessels may be,-and physiologists have long supposed it to be
      very great,-it certainly does not suffice to hinder blood service anywhere in the
      digestive tract. On the other hand the service to certain unessential abdominal
      organs (spleen, omentum, urinary bladder) is cut off in large part or wholly; and
      in comparison with the essential viscera, the skin and most of the skeletal
      muscles of the bled animal are largely deprived of circulation. This neglect
      takes a curious form, some regions being still fairly served by the blood while
      others next them are no longer ministered to. In the skin the areas served, or
      not served, are highly irregular but are to some extent determined in situation
      by local pressure factors. Within the muscles the neglect is orderly in
      arrangement and is largely referable to compensatory vaso-constriction. Certain
      of the muscles, those used in respiration and in swallowing, furnish significant
      exceptions to the general rule, being excellently served despite the serious
      general state. The red bone marrow of the depleted organism continues to be well
      served by the blood even though situated in limbs that are, for the rest, almost
      devoid of a circulation. The pregnant uterus also is excellently maintained
      despite the serious general state. The changes are such as would tend to conserve
      the forces of the depleted organism and to contribute to its recovery.

PMID- 19869615
TI  - STUDIES OF TISSUE MAINTENANCE : II. THE SERVICE TO THE LIVER AND DIGESTIVE TRACT
      AFTER HEMORRHAGE.
AB  - The vascular readjustments in compensation for a greatly reduced blood bulk
      affect the service rendered by the blood to the gastrointestinal tract and liver
      far less than they do that to the skin and muscles. Into these latter tissues
      india ink is carried almost not at all, whereas it circulates in quantity through
      the capillaries of the bowel and liver. Evidently vaso-constriction is much less
      effective in these viscera. Nowhere in them does one find a patchy ischemia like
      that so wide-spread in the peripheral tissues. Blood service is maintained to the
      same extent everywhere throughout the liver even when one of its two sources
      (hepatic artery or portal vein) is obstructed, and the intrahepatic blood
      pressure brought very low. A pronounced patchy ischemia of the stomach and large
      bowel can be induced by intravenous injection into normal animals of sufficient
      epinephrin to cause the systemic blood pressure to mount to an abnormally high
      level. Pituitrin used in the same way has a greater effect; blood service to the
      organs mentioned may be completely abolished by means of it. In both instances,
      though, service to the small gut and liver is still excellently and evenly
      maintained.

PMID- 19869616
TI  - THE EFFECT OF UNILATERAL NEPHRECTOMY ON THE TOTAL NUMBER OF OPEN GLOMERULI IN THE
      RABBIT.
AB  - 1. Under the experimental conditions employed, from 44 to 78 per cent of the
      glomeruli of the normal rabbit kidney contain circulating blood at any one
      moment. 2. After unilateral nephrectomy the number of glomeruli in the remaining
      kidney, which contain circulating blood, is increased to 91 to 99 per cent. 3.
      Compensation for the removal of one kidney is accomplished during the first 10
      days at least, by an increase of the number of open glomeruli in the opposite
      kidney.

PMID- 19869617
TI  - A STUDY OF PNEUMONIA IN A RURAL AREA IN SOUTHERN ALABAMA.
AB  - 1. Pneumococcus Type IV of low virulence was the prevailing organism in fifty
      eight cases of pneumonia studied in southern Alabama. Fixed types of pneumococci
      were not common. 2. Pneumoma was more prevalent in children from 5 to 15 years of
      age than in adults. As a rule, the disease ran a mild course. 3. Most of the
      cases of pneumonia gave a definite history of an acute cold antedating the attack
      of pneumonia by a period of 5 to 8 days. Exposure alone did not seem to
      predispose to pneumonia, but those with an acute cold who were exposed to
      chilling of the body surface frequently developed pneumonia. 4. There were seven
      "family epidemics" of pneumonia. In each instance there was a family epidemic of
      colds antedating the pneumonia. The pneumococcus was found in large numbers in
      the nasopharynx of those suffering from colds as well as in the pneumonia
      patients. 5. The epidemiology of pneumonia in the pioneer days of American
      history has many points in common with the epidemiology of pneumonia in a rural
      isolated area in southern Alabama today. This suggests that the crowded
      conditions and frequent contacts of modern city life have built up a community
      resistance to avirulent strains of pneumococci.

PMID- 19869618
TI  - STUDIES ON THE DISSOCIATION OF THE HOG CHOLERA BACILLUS : I. THE ISOLATION AND
      DIFFERENTIATION OF DISSOCIANTS.
AB  - When the "normal" MS form of hog cholera bacillus was grown for 3 weeks in broth
      and subsequently plated in semi-solid media, 2 variant forms appeared, a motile
      rough (MR) form and a nonmotile smooth (NS) form. The NS form subsequently gave
      rise to a third variant, namely, the nonmotile rough (NR) form. It is evident
      from the observations reported that in the case of the hog cholera bacillus the
      simple S and R conception of microbic dissociation is inadequate to account for
      the several variant forms. It appears necessary to combine the S and R with the H
      and O or the flagellar and somatic antigen conception to account for the
      phenomenon. The dissociation is represented by the following diagram: See PDF for
      Structure.

PMID- 19869619
TI  - STUDIES ON THE DISSOCIATION OF THE HOG CHOLERA BACILLUS : II. SEROLOGICAL
      REACTIONS, VIRULENCE AND STABILITY OF THE VARIANT FORMS.
AB  - The experiments recorded in the present paper confirm the existence of 4 forms of
      the hog cholera bacillus described in a previous paper (1), namely the "normal"
      type strain MS and its 3 variants, MR, NS and NR. Serological evidence is also
      presented to show that the symbols MS, MR, NS and NR represent the similar
      conceptions of previous investigators who have used the letters OH, O, OH and O
      respectively to designate variant forms of other organisms. It has been shown
      that the S form of the hog cholera bacillus, as the S forms of other bacteria, is
      more virulent for laboratory animals than the R forms. In regard to the
      reversibility of one form to another it was found that by transfer in broth or by
      passage through mice the MR form showed a tendency to revert to the original MS
      form. Transfer in broth and animal passage, however, failed to induce any
      variations in the NR or NS forms. Growth in homologous immune sera did not cause
      reversion to original forms but in fact provoked further dissociation of the MR
      to the NR form and also of the NS to the NR form. The MR form may revert to the
      original normal MS form or may dissociate further into the NR form and is,
      therefore, the most unstable of the variants. Further attempts to induce changes
      in the other variants were not made. The dissociation as observed may be
      represented thus: See PDF for Structure.

PMID- 19869620
TI  - RELATION OF VACCINAL IMMUNITY TO THE PERSISTENCE OF THE VIRUS IN RABBITS.
AB  - 1. By means of cataphoresis vaccine virus can be obtained from suspensions of
      tissue which are inactive by the usual tests of animal inoculation. 2. Active
      virus can be obtained by cataphoresis from the tissues of rabbits long recovered
      from the effects of cutaneous vaccination. 3. Evidence is brought forward which
      suggests that immunity in a virus disease, such as vaccinia, may be linked with
      the persistence in the body of living virus.

PMID- 19869621
TI  - THE EFFECT OF CATAPHORESIS ON POLIOMYELITIS VIRUS.
AB  - 1. Under ordinary conditions of hydrogen ion concentration the virus of
      poliomyelitis, as such, or associated with particles in fine suspension, migrates
      in an electrical field to the anode. It follows that the virus bears an
      electronegative charge. 2. By means of cataphoresis, the virus can be recovered
      from a non-infective mixture of virus and specific immune serum. 3. By the same
      means it is possible to reveal the presence of virus in the central nervous
      system of a monkey which has recovered from the active stage of experimental
      poliomyelitis.

PMID- 19869622
TI  - ADAPTATION OF MASTITIS STREPTOCOCCI TO MILK.
AB  - The data here presented indicate that the inhibitory principle affecting the
      growth of streptococci in milk is not greatly utilized during the lag phase and
      that the abrupt termination of lag is not due to the utilization of the
      principle. They further indicate that the sudden beginning of growth cannot be
      ascribed to a resistant type of streptococcus present in the culture from the
      first, but to an adaptation occurring during the lag phase. The addition of large
      numbers of dead or living streptococci to milk, for limited periods, fails to
      diminish appreciably the inhibitory principle.

PMID- 19869623
TI  - THE LESIONS IN THE SKELETAL MUSCLES IN EXPERIMENTAL SCORBUTUS.
AB  - 1. Muscle degeneration was constantly found in the intercostal muscles of
      scorbutic guinea pigs. 2. It has likewise been found in the masseter and
      diaphragmatic muscles. 3. Exercise will produce an identical lesion in other
      skeletal muscles in scorbutic animals. 4. The lesions appear to be an intrinsic
      part of the scorbutic process. 5. It is suggested that the tenderness over
      muscles in scorbutic animals and in man may be due to this myopathy.

PMID- 19869624
TI  - THE GERMICIDAL ACTION OF HYDROXY SOAPS.
AB  - 1. The alpha-hydroxy soaps exhibit a high germicidal action toward certain
      organisms. As with other soaps, the germicidal action increases with molecular
      weight to a maximum, then diminishes. The pH effects the germicidal action as it
      does other soaps. 2. Certain alpha-hydroxy soaps give two distinct germicidal
      zones with Staphylococcus aureus. 3. The effect of the hydroxyl group in
      saturated soaps is to increase selective germicidal action; the effect of the
      hydroxyl group in an unsaturated soap is to diminish it. 4. The soaps offer a
      means of separating mixtures of organisms by selective germicidal action.

PMID- 19869625
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : I. THE SPECIFIC FIXATION
      BY TISSUES OF SUSCEPTIBLE ANIMALS.
AB  - Ground muscle from susceptible chickens fixes in vitro in a proportion of
      instances the agent of the filterable Chicken Tumor I, and in a lesser degree
      inactivates it, whereas the muscle from resistant animals such as rabbit and
      pigeon, is without effect. It is shown that the power of fixation of the chicken
      muscle is far greater than its inactivating properties. Brain and liver from
      chicken, rabbit and pigeon seem devoid of any action on the agent. The desiccated
      chicken muscle tissue shares the properties of the fresh organ; and the process
      of desiccation does not release the agent from the inactive or slightly active
      mixture of fresh muscle and filtrate.

PMID- 19869626
TI  - THE EFFECT OF EXTRACTS OF CERTAIN ORGANS FROM NORMAL AND IMMUNIZED ANIMALS ON THE
      INFECTING POWER OF VACCINE VIRUS.
AB  - Brain and testicle tissue from immune rabbits brought in contact with the
      Levaditi or Noguchi strains of vaccine virus will fix or inactivate the virus.
      Extracts of normal testicles from susceptible animals enhance to an extraordinary
      degree the infectivity of both the neuro- and dermal strains of vaccine virus.
      The Noguchi virus is not affected by testicle extracts when injected into the
      skin, but kidney extract has a definite enhancing power on the strain when
      injected into either skin or testicle. The effect of tissue extracts seems to be
      on the cells of the host rather than on the virus. This is indicated by the fact
      that virus injected intravenously localizes most readily in an area of skin
      previously injected with testicle extract. Furthermore an enhanced lesion results
      if the virus is injected into an area as long as 3 days after the area has been
      injected with testicle extract. The augmenting substance of the tissue extracts
      is little affected by high dilutions, passes through a Berkefeld V candle and is
      carried down with the proteins precipitated by weak acids. Rabbits with enhanced
      lesions show general symptoms and about 25 per cent die with generalized
      vaccinia. Kidney, and probably skin, brain and liver extracts possess enhancing
      properties, but to a much less degree than the testicle. On the other hand,
      spleen, blood and probably lymph nodes and bone marrow not only fail to produce
      enhancement, but actually restrain or even suppress entirely the vaccinal skin
      infection.

PMID- 19869627
TI  - A STUDY OF THE GENERALIZATION OF VACCINE VIRUS FROM ENHANCED SKIN LESIONS.
AB  - Rabbits bearing very intensive skin lesions resulting from the intracutaneous
      injection of neurovirus plus testicular extract show typical histological
      alterations in the gonads, suprarenals, liver, spleen, lung, lymph nodes, and
      bone marrow. Similar but less wide-spread alterations are found after intravenous
      injection of neurovirus. Although testicle extract injected intracutaneously with
      neurovirus has a marked enhancing action upon the activity of the latter, the
      same mixture injected intravenously yields no sign of any such enhancement. The
      significance of these observations as regards the question of the
      ectodermotropism of vaccine virus is discussed, and the doctrine of specific
      organ affinities is considered.

PMID- 19869628
TI  - ETIOLOGY OF OROYA FEVER : XV. EFFECT OF IMMUNE SERUM ON THE COURSE OF BARTONELLA
      BACILLIFORMIS INFECTION IN MACACUS RHESUS.
AB  - Experiments are reported on the effect upon the course of experimental verruga
      peruana in Macacus rhesus of the injection of (1) small quantities of rabbit
      immune serum simultaneously with living cultures, (2) one large dose of
      convalescent monkey serum 24 hours prior to inoculation, (3) a similar
      preliminary dose followed by three subsequent injections of the serum, (4) three
      large doses of convalescent serum, following the inoculation. The convalescent
      serum was found (1) to prevent the multiplication of Bartonella bacilliformis in
      the blood in most instances, and (2) to delay the development of the skin lesions
      for considerable periods, when given before inoculation. When the serum treatment
      was not begun until after the appearance of the skin lesions, it had no effect on
      the progress of the nodules, although the blood became free from Bartonella
      bacilliformis. Since the severe effects of verruga peruana (Carrion's disease)
      are believed to be due to the multiplication of Bartonella bacilliformis within
      the blood, the injection of convalescent serum in cases of Carrion's disease in
      man would appear to offer promise.

PMID- 19869629
TI  - A PARALYTIC DISEASE OF GUINEA PIGS DUE TO THE TUBERCLE BACILLUS.
AB  - The experimental data collected during this study of a transmissible type of
      paralysis developing in tuberculous guinea pigs indicate the condition to be a
      true tuberculous meningitis. We have been able to rule out the possibility that
      it is due to a non-tuberculous infection of the central nervous system caused by
      Roemer's virus, or by an atypical herpes virus, or by some bacterium other than
      the tubercle bacillus. Roemer's virus and herpes could be eliminated from
      consideration when Berkefeld N filtrates of infectious brain emulsions proved
      incapable of reproducing the disease. Furthermore, rabbits could be infected as
      they cannot with Roemer's virus, and the disease elicited in rabbits bears no
      semblance to herpes encephalitis. No organism other than the tubercle bacillus
      could be obtained on culturing brain or brain emulsions from experimental cases,
      and no others were seen in examining fresh smear preparations from the central
      nervous system. In a modified Noguchi medium a tubercle bacillus possessing
      atypical staining properties was obtained. This organism was capable of producing
      the typical paralytic disease when injected intracerebrally into guinea pigs, and
      also generalized tuberculosis in animals inoculated subcutaneously with it.
      Typical tuberde bacilli were readily demonstrable in sections of the meninges
      from animals with the disease, and culture of pieces of brain on Dorset's egg
      medium usually yielded a growth of tubercle bacilli. Only in the first of the
      experimental passages, on the other hand, was it possible to demonstrate acid
      fast organisms in fresh smear preparations from the central nervous system. This
      fact and the attributes of the atypically staining organisms encountered in the
      cultures in Noguchi media will be considered more fully in a subsequent
      publication. In view of the much discussed question of the filtrability of the
      tubercle bacillus our observations concerning the failure of this organism to
      pass a Berkefeld N filter are of interest. No animal in our series inoculated
      intracerebrally with brain emulsion from either a "spontaneous" or experimental
      case of tuberculous meningitis failed to develop meningitis, and that rather
      acutely, while no animal in our series injected with a Berkefeld filtrate of
      brain emulsion has developed tuberculous meningitis or any other form of
      tuberculosis. In connection with this observation it must be recalled that the
      organism was atypical in respect to its staining qualities at least.

PMID- 19869630
TI  - THE CULTURAL AND STAINING REACTIONS OF A STRAIN OF THE TUBERCLE BACILLUS
      PRODUCING PARALYSIS IN GUINEA PIGS.
AB  - When a strain of human tuberculosis was carried from guinea pig to guinea pig by
      intracerebral inoculation the bacillus of tuberculosis could be readily recovered
      in the semisolid "Leptospira" medium of Noguchi simply modified by the
      substitution of guinea pig for rabbit serum. Whether even this modification is
      required remains to be determined. The tubercle bacillus in these cultures and
      possibly in the nervous tissue as well differed from the classical type in that
      it was less acid-fast and quite lacking in alcohol fastness. However, it retained
      the Gram stain as modified by Much. Staining reactions, as this culture of the
      tubercle bacillus shows, are not absolute qualities but are variable with
      conditions, a consideration which it may be important to recognize. Efforts to
      define these conditions more precisely are likely to be productive.

PMID- 19869631
TI  - THE REMOVAL OF AGGLUTININ FROM SENSITIZED MOTILE BACTERIA : SECOND PAPER. THE
      AGGLUTINATIVE PROPERTIES OF WATER WASHINGS.
AB  - The salt-free water washings of a sensitized motile bacterium (B. aertrycke) were
      found to cause a floccular agglutination in the presence of both whole and
      deflagellated antigen. Evidence was presented that the water washings when salt
      free contained flagella and flagellar agglutinin and that clumping occurred upon
      the addition of saline. The floccular reaction in the presence of deflagellated
      bacteria was regarded as the agglutination of flagella present in the washings.
      In the presence of whole bacteria, however, actual bacterial agglutination
      resulted.

PMID- 19869632
TI  - THE EFFECTS OF LOSS OF GASTRIC AND PANCREATIC SECRETIONS AND THE METHODS FOR
      RESTORATION OF NORMAL CONDITIONS IN THE BODY.
AB  - The composition of gastric and pancreatic juices and the effects of their loss on
      the composition of the body fluids were studied. Loss of gastric juice by
      removing water and chloride ions only partly neutralized by fixed base results in
      dehydration and alkalosis. Loss of pancreatic juice by removing water and a
      relative excess of fixed base results in dehydration and acidosis. Normal
      conditions in the body may be restored after the loss of either gastric or
      pancreatic juice by the administration of a combined solution, which provides (1)
      water in abundance because of its hypotonicity (2) an adequate source of the
      fixed anion Cl' and of the cations Na(+), K(+), and Ca(++) in proper
      physiological ratio and (3) an excess of fixed base over fixed acid in the form
      of B-lactate.

PMID- 19869633
TI  - SEROLOGICAL DIFFERENTIATION OF STERIC ISOMERS (ANTIGENS CONTAINING TARTARIC
      ACIDS) : SECOND PAPER.
AB  - In continuation of studies on the stereochemical specificity of serum reactions,
      antigens were examined containing the acyl radicals of the levo-, dextro-, and
      meso-tartaric acids. It was found that in this case also, immune sera can readily
      be obtained which differentiate sharply the three antigens identical in every
      other respect but possessing stereoisomeric groups. Since the tartaric acids by
      their chemical constitution belong to the same class of substances as sugar acids
      the results have a bearing upon the question of the specificity of natural
      antigens containing carbohydrates such as have been described by Avery and
      Heidelberger.

PMID- 19869634
TI  - THE ANTIBODY-FORMATION BY POLYSACCHARIDS.
AB  - 1. By complement fixation tests, it has been clearly demonstrated that the sera
      of rabbits immunized with inulin, soluble starch and dextrine contain specific
      antibodies. 2. All these immune sera gave a negative precipitation reaction. 3.
      The kind of dextrine which has a construction very near to starch has an
      antigenic property, but those in a state of further decomposition do not give
      rise to antibodies. 4. All the three kinds of polysaccharids have power to
      produce antibodies without any vehicle. Dextrine is the only one of the three
      that gives rise to immune bodies more readily when pig serum is added to it. 5.
      Regarded as antigens, inulin stood first and soluble starch and dextrine next in
      order. 6. All three kinds of polysaccharids that were employed gave a negative
      protein color reaction. All of them, however, contained nitrogen. It has been
      proved that the large portion of the nitrogen contained in the soluble starch is
      derived from its protein contents. 7. It is suggested that in the production of
      immune bodies by these three kinds of polysaccharids, proteins might play the
      part of the vehicle. This is, however, still to be determined.

PMID- 19869635
TI  - THE ANTIBODY RESPONSE IN THE HUMAN BEING AFTER INJECTION WITH NORMAL HORSE SERUM.
AB  - After the injection of normal horse serum in the human being, serum sickness
      occurs even more regularly than in cases treated with the various immune sera,
      but this is not accompanied by the production, to any notable degree, of
      circulating antibodies of the various types that are regularly to be demonstrated
      after the administration of immune serum and its resulting serum sickness. Since
      normal horse serum therefore appears to be weakly antigenic, and immune serum
      highly antigenic for the human being, one must assume that this difference is the
      result of some alteration in its antigenic characteristics produced during the
      course of the immunization or of its preparation for use; or that the specific
      antibody which is responsible for the phenomenon of serum sickness has not yet
      been identified; or that this phenomenon is not in any way dependent on the
      presence of the various known antibodies to normal horse serum.

PMID- 19869636
TI  - THE EFFECTS OF CATHODE RAYS ON THE PROTEINS OF SERUM.
AB  - The effects of cathode rays on the proteins of serum appear to be (1)
      denaturation of a large proportion of the albumin and globulin with the formation
      of products that are soluble at the pH of the serum; (2) the production of a
      tough and exceedingly insoluble substance on the window of the cell where most of
      the absorption of electrons occurs; (3) a slight hydrolytic cleavage of the
      protein molecule producing a small quantity of products having properties so near
      to those of the protein that they are precipitated by trichloracetic acid but are
      not removed by coagulation at the isoelectric point; (4) the production of a
      small amount of hydrolytic products not precipitated by trichloracetic acid; and
      (5) the formation of a small amount of ammonia, part of which at least is derived
      from the urea in the serum. It is interesting to note that these changes are such
      as would bring about exactly those effects on fibroblasts which were observed
      when cultures were grown in serum which had been subjected to cathode ray
      irradiation. The proteins of serum have a retarding effect on the growth of
      fibroblasts. We might, therefore, expect their removal by denaturation and
      coagulation to result in the slightly larger growth which was observed. The
      production of SH groups in the denatured protein molecule would also tend to have
      a beneficial effect, as has been observed in experiments with denatured albumin.
      A concentration of protein split products equal to that in the irradiated sera
      has been observed to produce cells of characteristic appearance, full of
      cytoplasmic granulations and possessing long, active pseudopods, such as those
      noted in colonies cultivated in serum which had been subjected to cathode rays.

PMID- 19869637
TI  - CELL PROLIFERATION RESPONSE TO SULFHYDRYL IN MAMMALS.
AB  - These experiments establish the fact that the sulfhydryl group is stimulative of
      cell proliferation in mammals as in lower organisms. The fact that the
      stimulation is exhibited in such a wide diversity of species including both
      plants and animals is justification for the belief that it is the expression of a
      fundamental biological phenomenon. The literature and discussion of the subject
      are to be found in the papers cited.

PMID- 19869638
TI  - ANTIBODY AND AGGLUTININ IN PNEUMOCOCCUS PNEUMONIA.
AB  - 1. Protective substances and agglutinins were not demonstrated in the blood of
      patients with pneumonia untreated with serum before the fall in the temperature
      by crisis or lysis. 2. Protective substances and agglutinins were frequently
      demonstrated in serum treated patients during the course of the disease. 3.
      Protective substances and agglutinins were usually present at the time of the
      temperature fall in patients untreated with serum and persisted for days or weeks
      thereafter. 4. Protective substances have an important bearing on the outcome. A
      large proportion of those with protection recover and a large proportion without
      it die. 5. Agglutinin and antibody may appear simultaneously or one may precede
      or be present without the other. 6. Tests for agglutinin are unreliable as a
      control of dosage of specific serum.

PMID- 19869639
TI  - ETIOLOGY OF OROYA FEVER : XVI. VERRUGA IN THE DOG AND THE DONKEY.
AB  - In the experiments here reported, definite verruga lesions, in which the presence
      of Bartonella bacilliformis was established by culture or by passage to rhesus
      monkeys, were produced in a dog and in a donkey by inoculation of cultures or
      monkey passage strains. The reaction induced in these animals was entirely local,
      however; blood cultures were sterile. Histologically, the lesions produced were
      similar to those obtained in monkeys by inoculation of Bartonella bacilliformis,
      except for the presence of a marked polynuclear leucocytic exudate. In another
      donkey a lesion histologically suggestive of verruga was produced, while in one
      donkey and a horse the results of inoculation were negative or indefinite. The
      intravenous injection of a filtrate or of heat-killed cultures of Bartonella
      bacilliformis into two donkeys was followed by the appearance of large, soft,
      subcutaneous swellings, on various parts of the body, not resembling in any way
      verruga lesions.

PMID- 19869640
TI  - DIFFERENTIATION OF HEMOLYTIC STREPTOCOCCI OF HUMAN AND OF DAIRY ORIGIN BY
      METHYLENE BLUE TOLERANCE AND FINAL ACIDITY.
AB  - A grouping of 138 strains of hemolytic streptococci based on differences in dye
      sensitiveness and in final hydrogen-ion concentration of cultures is presented.
      Three groups are distinguished; (1) human parasitic strains, defined by a final
      pH range of 5.2 to 5.0 and by failure to reduce methylene blue (1:5000) in milk,
      (2) bovine strains parasitic in the udder, characterized by a final pH range of
      4.5 to 4.2 and by failure to reduce methylene blue (1:5000) in milk, (3)
      saprophytic strains, characterized by a final pH range of 4.5 to 4.2 and by
      ability to reduce methylene blue. Methylene blue was bactericidal for the strains
      of hemolytic streptococci that fail to reduce it, but neither bacteriostatic nor
      bactericidal for the strains that caused its reduction.

PMID- 19869641
TI  - STUDIES OF TISSUE MAINTENANCE : III. PERSISTING BLOODLESSNESS AFTER FUNCTIONAL
      ISCHEMIA.
AB  - In skin regions which have been bloodless for some time, as result of the
      functional readjustments following upon a reduction of the blood bulk, the
      ischemia persists long after the blood volume has been restored and the systemic
      blood pressure has mounted to the initial level or a higher one. The significance
      of the finding is briefly discussed.

PMID- 19869642
TI  - THE FINAL RESPONSE OF THE SMALL CUTANEOUS VESSELS.
AB  - A study of the blanchings (Bier's spots) which develop in human skin deprived of
      circulation has proved them referable to the same general causes that lead to
      ischemic patching of the skin of animals, and that they are conditioned by the
      same factors. Both are expressions of a secondary contraction of vessels that
      have become hyperirritable owing to an inadequate circulation. The contraction is
      favored by emptying the vessels, but it occurs pronouncedly even when there is a
      trickle through them of arterial blood. In the case of man the contractile
      impulse is sometimes so great as to overcome the maximum pressure that the
      vessels will support. The significance of the observations is discussed.

PMID- 19869643
TI  - STUDIES ON BACILLUS TYPHOSUS TOXIC SUBSTANCES : III. THE EFFECT OF SERA UPON THE
      INJURY PRODUCING FACTORS OF THE PHENOMENON OF LOCAL SKIN REACTIVITY.
AB  - It has been demonstrated that many multiples of minimal doses of Bacillus
      typhosus reacting factors can be neutralized by specific immune sera. The potency
      of a given serum can be conveniently titrated against increasing amounts of
      reacting factors. If the immune serum is diluted or if the amount of the reacting
      factors is too large for a given amount of serum, there is obtained
      neutralization but only irregularly. Normal and heterologous sera (therapeutic
      meningococcus and erysipelas horse sera) free of normal agglutinins or possessing
      normal agglutinins of a low titer (1:16) for Bacillus typhosus are not able to
      neutralize the reacting factors. There is obtained questionable neutralization
      with a serum possessing normal Bacillus typhosus agglutinins in dilution 1:64.
      The titer of the neutralizing antibodies increases in the course of immunization.
      Immune sera exercise a definite protection against the mortality induced by
      intravenous injection of Bacillus typhosus culture filtrates.

PMID- 19869644
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : I. THE
      SYNTHESIS OFp-AMINOPHENOL beta-GLUCOSIDE, p-AMINOPHENOL beta-GALACTOSIDE, AND
      THEIR COUPLING WITH SERUM GLOBULIN.
AB  - It has been demonstrated that many multiples of minimal doses of Bacillus
      typhosus reacting factors can be neutralized by specific immune sera. The potency
      of a given serum can be conveniently titrated against increasing amounts of
      reacting factors. If the immune serum is diluted or if the amount of the reacting
      factors is too large for a given amount of serum, there is obtained
      neutralization but only irregularly. Normal and heterologous sera (therapeutic
      meningococcus and erysipelas horse sera) free of normal agglutinins or possessing
      normal agglutinins of a low titer (1:16) for Bacillus typhosus are not able to
      neutralize the reacting factors. There is obtained questionable neutralization
      with a serum possessing normal Bacillus typhosus agglutinins in dilution 1:64.
      The titer of the neutralizing antibodies increases in the course of immunization.
      Immune sera exercise a definite protection against the mortality induced by
      intravenous injection of Bacillus typhosus culture filtrates.

PMID- 19869645
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : II.
      IMMUNOLOGICAL SPECIFICITY OF SYNTHETIC SUGAR-PROTEIN ANTIGENS.
AB  - 1. When two chemically different carbohydrate derivatives are bound to the same
      protein, the newly formed antigens exhibit distinct immunological specificity. 2.
      When the same carbohydrate radical is conjugated with two chemically different
      and serologically distinct proteins both of the sugar-proteins thus formed
      acquire a common serological specificity. 3. The newly acquired specificity of
      the artificially prepared sugar-proteins is determined by the chemical
      constitution of the carbohydrate radical attached to the protein molecules.
      Simple differences in the molecular configuration of the two isomers,-glucose and
      galactose-suffice to orientate protein specificity when the corresponding
      glucosides of the two sugars are coupled to the same protein. 4. The unconjugated
      glucosides, although themselves not precipitable in immune serum, inhibit the
      reaction between the homologous sugar-protein and its specific antibody. The
      inhibition test is specific. 5. The sugar derivatives unattached to protein
      exhibit the properties of carbohydrate haptens; they are non-antigenic but
      specifically reactive, as shown by inhibition tests, with antibodies induced by
      proteins containing the homologous diazotized glucoside. 6. The specificity of
      artificially prepared sugar-proteins is discussed with reference to the chemo
      immunological nature of the bacterial antigens containing complex sugars.

PMID- 19869646
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : III. ACTIVE AND
      PASSIVE ANAPHYLAXIS WITH SYNTHETIC SUGAR-PROTEINS.
AB  - 1. Guinea pigs passively sensitized with the serum of rabbits immunized with an
      artificially prepared sugar-protein (gluco-globulin) exhibit typical anaphylactic
      shock when subsequently inoculated with gluco-albumin; the serum of rabbits
      immunized with a second synthetic sugar-protein (galacto-globulin) similarly
      sensitizes guinea pigs to galacto-albumin. The reactions, in each instance, are
      specific and depend for their specificity on the carbohydrate component, and not
      on the protein fraction of the synthesized sugar-protein. 2. Guinea pigs actively
      sensitized with gluco-globulin or galacto-globulin are similarly subject to
      anaphylactic shock, when injected, after 21 days, with sugar-proteins containing
      carbohydrate identical with that present in the sensitizing antigen, regardless
      of the kind of protein with which it is combined. 3. The unconjugated glucosides,
      although themselves not capable of inducing shock, inhibit the anaphylactic
      reaction when injected immediately prior to the introduction of the toxigenic
      sugar-protein. The protective action of the glucosides disappears within two
      hours after injection. In order to elicit the phenomenon, the carbohydrate must
      be the same as that combined in the sugar-protein complex. 4. Anaphylactic shock
      may be induced by uncombined globulin in guinea pigs passively sensitized with
      either antigluco-globulin serum or antigalacto-globulin serum; globulin is
      similarly effective in animals actively sensitized with gluco-globulin or galacto
      globulin. The reactions elicited by globulin alone are dependent upon the common
      protein present in the antigens, and exhibit only species specificity.

PMID- 19869647
TI  - THE LIVER AS THE SOURCE OF FIBRINOGEN.
AB  - In hepatectomized rabbits a progressive decrease in blood fibrinogen occurs.
      Partial defibrination in the liverless rabbit invariably results in a progressive
      decrease in blood fibrinogen preceded by a temporary and slight rise. No evidence
      has been secured of fibrinogen regeneration in the absence of the liver. From
      this it follows that the liver is the essential source of fibrinogen and in all
      probability the sole one.

PMID- 19869648
TI  - STUDIES ON IMMUNOLOGICAL RELATIONSHIPS AMONG THE PNEUMOCOCCI : IV. ACTIVE
      IMMUNIZATION OF MICE AGAINST TYPE II PNEUMOCOCCI BY VACCINATION WITH YEAST.
AB  - Mice vaccinated with yeast were protected against subsequent infection with Type
      II pneumococci, but not against Types I or III. While the protection was not
      universal, as high a percentage of mice acquired active anti-Type II immunity, as
      was obtained by vaccination of another group of mice with Type II pneumococci
      themselves. This specific protection of mice by active immunization with the
      yeast antigen, is probably due to the same immunological relationship responsible
      for the anti-Type II reactivity of the antisera of rabbits immunized with yeast
      antigen.

PMID- 19869649
TI  - INFECTIVITY OF BLOOD DURING THE COURSE OF EXPERIMENTAL YELLOW FEVER.
AB  - Five M. rhesus fatally infected with yellow fever virus ran varied and typical
      courses, death occurring from 82 hours to 10 days after infecting. Batches of A.
      aegypti were fed daily on each monkey and specimens of blood injected into other
      animals. By mosquito transfer, the virus was found to be circulating in the
      peripheral blood 1 or 2 days after the infecting and the same interval before the
      onset of fever; in one instance, mosquitoes became infectious by feeding on a
      monkey 12 hours after its inoculation. Mosquitoes continued to acquire
      infectivity during the febrile period and for 1 day thereafter, except in one
      instance when death occurred during fever which prevented post-febrile testing.
      By subinoculation of blood, the disease was transferred before and after, as well
      as during the same interval as in mosquito transmission. In one of two attempts,
      the virus was carried by this means as early as 12 hours after the donor animal
      was infected. Following the first day of the post-febrile period, blood
      transmissions were irregularly fatal beyond the period infective for mosquitoes.
      These results point to a remarkably rapid multiplication of the virus in the
      animal host, in one case a blood subinoculation (0.5 cc.) being successful at the
      first test 24 hours after the donor monkey was bitten by only 2 A. aegypti. The
      regular acquisition of infectivity by mosquitoes fed during the incubation period
      is of especial interest in indicating the infectivity of human cases for
      mosquitoes before the appearance of clinical symptoms. This offers one
      explanation for the insidious propagation of epidemics of yellow fever and should
      be useful in the institution of control activities during an outbreak of this
      disease.

PMID- 19869650
TI  - A MECHANISM OF CONSERVATION IN THE KIDNEYS OF THE WINTER FROG.
AB  - 1. A method of conservation has been demonstrated in the kidneys of winter frogs.
      2. The mechanism of this conservation is an increase in the absorptive function
      and a decrease in the excretory activity of the tubular epithelium. 3. The
      excessive absorptive process may be depressed by various means. Such a depression
      in the tubular activity is followed by large increases in the rate of excretion
      of water, salts and, if present in the urine, phenol red. 4. Further evidence is
      thus obtained which supports the theory that phenol red is excreted chiefly
      through the glomeruli.

PMID- 19869651
TI  - BACTERIOLOGY OF THE BLOOD AND JOINTS IN RHEUMATIC FEVER.
AB  - 1. During the Spring of 1928, 29 patients with acute rheumatic fever were
      subjected to blood cultures, of whom 9, or 31 per cent, yielded a streptococcus.
      During the Spring of 1929, 31 patients with acute rheumatic fever were studied by
      blood cultures, of whom 26, or 83.9 per cent, yielded a streptococcus. The higher
      percentage of positive cultures in the 1929 series appears to have been due to
      improved cultural methods. 2. Of the 35 strains of streptococci recovered from
      blood cultures, 33 have been classified as alpha streptococci (Str. viridans);
      one as a beta streptococcus (Str. hemolyticus); and one a gamma streptococcus
      (Str. anhemolyticus). Some of the viridans strains produced very little green on
      blood media. 3. Agglutination and absorption tests indicate that the strains of
      streptococcus viridans recovered from the blood of patients with rheumatic fever
      show a tendency to fall into specific biological groups. 4. In 7 patients with
      rheumatic fever who were subjected to cultures from affected joints, 5, or 71.4
      per cent, yielded a streptococcus viridans. In 3 patients in whom green
      streptococci were recovered from both the blood and joint, agglutination and
      absorption tests proved the identity of the strains isolated from the two
      sources. 5. These findings corroborate those of previous investigators and make
      it difficult to escape the conclusion that rheumatic fever is a streptococcal
      infection usually of the alpha or viridans type. 6. The pathogenesis of rheumatic
      fever in respect to the joint lesions appears to be analogous to that of
      infectious arthritis and gonococcal arthritis. Bacterial allergy probably
      influences the clinical picture in all three conditions, but in each instance the
      joint manifestations are primarily dependent upon localization of bacteria in the
      joint, with subsequent infection.

PMID- 19869652
TI  - NASOPHARYNGEAL FLORA IN HEALTH AND DURING RESPIRATORY DISEASE IN ISOLATED
      COMMUNITIES IN ALABAMA AND LABRADOR.
AB  - Studies of the bacterial flora of the nasopharynx were made in isolated
      communities in South Alabama and Labrador. The basic flora was determined in both
      communities. In Alabama an epidemic of common colds was studied. In Labrador
      cases of sporadic colds and an epidemic of tracheitis were studied. Gram-negative
      cocci were found in nearly all normal individuals in moderate numbers. In
      pathological states there was a suppression of these organisms. Staphylococci
      were found in small numbers in about half of the normal individuals. In
      pathological conditions they disappeared from most of those affected but were
      found in increased numbers in a few individuals. Pfeiffer bacilli were absent or
      present only in small numbers in normal individuals. During the epidemic of colds
      in Alabama there was an increase in the number of strains recovered and an
      increase in the relative numbers of the bacilli in each throat. The highest
      prevalence was found one month after the epidemic had reached its height. In
      Labrador a similar increase was coincident with an epidemic of tracheitis. During
      normal periods the majority of the Pfeiffer strains were of the para non-indol
      forming type. During epidemic periods the strains recovered were largely true
      indol-forming B. Pfeifferi. Hemolytic streptococci were rarely found in normals.
      During disease prevalence periods they appeared in a small number of persons. In
      Alabama, indifferent streptococci resembled the hemolytic streptococci in their
      distribution. In Labrador they were found to be widely distributed in both health
      and disease and composed apparently a part of the normal flora. Green
      streptococci were found to be widely distributed in fairly large numbers both in
      health and disease. Intermediates, or organisms midway between green streptococci
      and pneumococci, were found in moderate numbers in each series of persons
      studied. Early in the Alabama epidemic they were present in large numbers in
      nearly all persons. Pneumococci were not found in Alabama in normal individuals.
      The epidemic of colds in Alabama was accompanied by a marked increase in the
      incidence of these organisms. In Labrador pneumococci seemed to be part of the
      normal flora as they were generally distributed throughout the community, in many
      instances comprising a large proportion of the flora of an individual's throat.
      The Labrador strains of pneumococci were avirulent. A variety of other organisms
      such as diphtheroids, Gram-negative rods, and Gram-positive cocci were found in
      small numbers in many individuals both in health and disease.

PMID- 19869653
TI  - DEVELOPMENT IN TISSUE CULTURES OF THE INTRACELLULAR CHANGES CHARACTERISTIC OF
      VACCINAL AND HERPETIC INFECTIONS.
AB  - Characteristic vaccinal and herpetic lesions, including Guarnieri bodies and
      acidophilic nuclear inclusions respectively, regularly occur in rabbit corneas
      infected and cultivated in vitro according to the method here described.

PMID- 19869654
TI  - A STUDY OF VACCINAL IMMUNITY IN TISSUE CULTURES.
AB  - Normal corneas inoculated in vitro with vaccine virus and then cultivated in
      antivaccinal plasma developed typical vaccinal lesions associated with Guarnieri
      bodies. In such cultures, after an incubation period of 24 or 48 hours, active
      vaccine virus was demonstrated by means of appropriate methods. Immune corneas
      inoculated in vitro with vaccine virus and then cultivated in normal or in
      antivaccinal plasma revealed either very mild vaccinal lesions or none at all. In
      some of the cultures after 24 and 48 hours of incubation, active vaccine virus
      was demonstrated.

PMID- 19869655
TI  - CUTANEOUS REACTIONS TO THE POLYSACCHARIDES AND PROTEINS OF PNEUMOCOCCUS IN LOBAR
      PNEUMONIA.
AB  - I. a. Pneumococcus polysaccharides, when injected intradermally into patients
      convalescent from pneumonia, are capable of eliciting a response. The
      polysaccharide inducing a cutaneous reaction was found always to be homologous in
      type to that of the pneumococcus causing the infection. b. The character of the
      reaction incited by the protein-free bacterial sugars is of the immediate wheal
      and erythema type. c. A patient's capacity to react was found to be intimately
      associated both with recovery from infection and with the presence of type
      specific antibodies in the circulating blood. II. a. The so-called nucleo-protein
      of pneumococcus, when injected intradermally, also causes a local cutaneous
      reaction in patients during convalescence from lobar pneumonia. b. The local
      lesion resulting from the injection of protein is tuberculin-like in character,
      and differs from that evoked by the type-specific polysaccharides in gross
      appearance, time of development, and duration. c. Individuals, acutely ill with
      and convalescent from pneumococcus pneumonia, possess in their circulating blood,
      precipitins reactive with pneumococcus protein. In the observations recorded, the
      concentration of anti-protein antibodies in the blood serum did not seem to
      influence the patient's capacity to react to intradermal injection of the
      protein.

PMID- 19869657
TI  - NUMBER OF GLOMERULI IN KIDNEY OF ADULT WHITE RAT UNILATERALLY NEPHRECTOMIZED IN
      EARLY LIFE.
AB  - Unilateral nephrectomy during the period of active nephrogenesis in the white rat
      has no effect on the total number of glomeruli which will be formed in the
      opposite kidney.

PMID- 19869656
TI  - POSSIBILITY OF HEREDITARY TRANSMISSION OF YELLOW FEVER VIRUS BY AEDES AEGYPTI
      (LINN.).
AB  - Attempts to obtain passage of yellow fever virus from one generation to the next
      in A. aegypti were unsuccessful. Subcutaneous injections at varying intervals of
      a saline emulsion of 200 eggs laid by an infective lot of mosquitoes produced no
      reaction in six normal M. rhesus monkeys. Negative results were also obtained in
      five biting and two injection experiments with progeny of the same infective lot
      of mosquitoes in which seven normal monkeys were used. The eggs consisted of
      batches laid after the first, second and fourth blood-meals of the original lot;
      the latter feeding occurred 41 days after the initial infecting meal. The
      imaginal offspring represented rearings following the first, second and fifth
      blood-meals of the parent lot. The last feeding occurred 54 days after the first.
      It is concluded that under the conditions of the experiments here reported
      hereditary transmission of yellow fever by A. aegypti is improbable. Variations
      in age and in number of blood-meals of parent and offspring mosquitoes had no
      effect in achieving passage of the virus from one stage of the insect to another.

PMID- 19869659
TI  - THE BLOOD IN HOG CHOLERA.
AB  - 1. Prolonged and systematic examination of blood from swine with hog cholera has
      failed to reveal any formed element that could be identified with the etiological
      virus. Culture has likewise been unsuccessful. 2. The quantitative blood changes
      in hog cholera consist in a slowly progressive anemia, usually moderate in
      degree, and a rapidly progressive severe leucopenia affecting cells of the
      polymorphonuclear series most markedly but also including those of the
      lymphocytic series. 3. Incubation of hog cholera blood results in a further
      progress of the leucopenia, in vitro, if heparin has been used as the
      anticoagulant, but there is no significant change if potassium oxalate or sodium
      citrate has been used. 4. Consideration of the leucocytic reactions prevailing in
      experimental infection with B. suisepticus, in infectious enteritis, in swine
      influenza, following successful immunization against hog cholera, and following
      infection of cholera-sick swine with secondary invaders indicates that the
      leucocyte count would be of aid in the differential diagnosis of hog cholera.

PMID- 19869658
TI  - THE FILTRABILITY OF YELLOW FEVER VIRUS AS EXISTING IN THE MOSQUITO.
AB  - The virus of yellow fever as it exists in Aedes aegypti mosquitoes, both in their
      so-called infective stage and in the intermediate condition termed the
      "incubation period", is capable of passing through Berkefeld N filters when
      suspended in normal monkey serum, although earlier investigators have shown that
      the virus from infective mosquitoes will not do so when suspended in
      physiological salt solution. The virus of yellow fever as it exists in mosquitoes
      behaves with regard to filtration through Berkefeld N filters as does the virus
      in the blood of infective monkeys.

PMID- 19869660
TI  - THE ELECTRICAL CHARGE OF BACTERIOPHAGE.
AB  - 1. Two types of cataphoresis apparatus for determining, under aseptic conditions,
      the charge carried by biologically active substances, such as Bacteriophage are
      described. One cell depends upon the electrophoresis of particles into agar and
      their subsequent re-suspension in a fluid medium for testing purposes. This cell
      has certain advantages when employed in connection with agents of small
      dimensions ordinarily inactivated by prolonged exposure to required test
      conditions. 2. Several separate races of anti-coli Bacteriophage have been found
      to bear a negative charge within a range of H-ion concentrations from pH. 9.0 to
      pH. 3.4. At pH. 3.35 and below, the lytic particles migrate through agar to the
      cathode. It is likely that the reversal in direction of migration is due to the
      assumption of a positive charge by the Bacteriophage corpuscle.

PMID- 19869661
TI  - THE FATE OF TUBERCLE BACILLI IN THE ORGANS OF REINFECTED RABBITS.
AB  - In agreement with previous work (6) it was found that in normal rabbits after a
      primary inoculation of 0.01 mg. of human tubercle bacilli the organism shows a
      preliminary growth, which commences at once in all the organs, and reaches its
      height in the second week in the liver, spleen, and bone marrow; thereafter
      destruction begins, and is practically complete by the sixth week in the liver
      and bone marrow and less complete in the spleen. In the lung and kidney the
      largest number are isolated in the fourth week and thereafter there is a tendency
      to destruction, but to destruction far less complete than in the other organs,
      for even two months after infection large numbers of tubercle bacilli persist.
      Associated with this multiplication of the human tubercle bacilli were found
      extensive or moderate tuberculous lesions in the lung and kidney with moderate or
      slight changes in the liver, spleen and bone marrow. In contrast to these
      observations, it was found that in rabbits reinfected with the same quantity of
      human tubercle bacilli, the organism was destroyed immediately without any
      preliminary multiplication in the liver, spleen and bone marrow, though a few
      bacilli persisted in these organs even two months after reinfection. Neither
      could definite evidence of multiplication of the tubercle bacilli of reinfection
      in the lung and kidney of these rabbits be obtained; although variable and at
      times very large numbers of tubercle bacilli persisted in these organs, probably
      due to the primary infection. Nor were tuberculous changes found in any of the
      organs due to reinfection. Again in rabbits that received a primary inoculation
      of 0.01 mg. of bovine tubercle bacilli the organism multiplied in all the organs.
      This multiplication reached its height in the liver, spleen and bone marrow
      between the fourth and sixth week, instead of in the second week as with human
      bacilli. Thereafter destruction was practically complete in the liver and much
      less complete in the spleen and bone marrow; in the lung and kidney
      multiplication continued unabated to the second month. Associated with these
      bacteriological data, there developed a massive pulmonary tuberculosis with
      extensive or moderate disease in the kidney, spleen, bone marrow and liver. In
      rabbits reinfected with the same quantity of bovine tubercle bacilli after a
      primary infection with human tubercle bacilli, the organism, in all but a few
      instances, was destroyed immediately in the liver, spleen and bone marrow. Here
      again, with the bovine type as with the human type, after reinfection as after
      primary infection, the destruction was not quite complete and a few isolated
      bacilli persisted even two months after reinfection. As to the lung and kidney,
      evidence was obtained that the variable and at times very large numbers of
      tubercle bacilli that were found in these organs were of human type in their
      cultural characteristics, and that in these organs also, the bovine tubercle
      bacilli of reinfection failed to grow. There was also as a rule complete absence
      of any tuberculous lesions in the liver, spleen and bone marrow. Nor were there
      any tuberculous changes found in the lung and kidney due to the reinfection, but
      those variable residual lesions that were found were present before reinfection,
      as shown in the lung by x-ray photographs. There were a few instances in which
      restricted multiplication of the virus took place and slight tuberculous lesions
      developed after reinfection in rabbits in which the primary lesions had all but
      disappeared. Thus in rabbits having considerable residual lesions from a primary
      human infection the tubercle bacilli of reinfection, whether human or bovine, are
      destroyed immediately though incompletely without any preliminary multiplication.
      Yet these rabbits, which so efficiently destroy the more virulent bovine bacilli
      of reinfection introduced from without, at times harbor tremendous numbers of
      human tubercle bacilli in the old lesions of the lung and kidney. Parallel with
      the bacteriological and pathological studies of these rabbits, the serum of some
      of them was studied for the presence of circulating antibodies by McCutcheon,
      Strumia, Mudd (S), Mudd (E. B. H.) and Lucke (7). These investigators found that
      on primary infection there was only a slight and slowly developing production of
      agglutinating and phagocytosis-promoting antibodies whereas, in the reinfected
      rabbits, which showed an immediate destruction of the bacilli, these antibodies
      rose promptly and in relatively large amount. They suggest that the prompt rise
      of antibodies in reinfected animals may play a role in the immunity to
      tuberculosis. In the previous study, which was preformed in 1927, emphasis was
      placed upon the comparatively slower original rate of growth of the bovine
      bacillus in the rabbit as compared with that of the human type, and in this delay
      was seen a partial explanation of the greater virulence of the bovine organism
      for this species. The more rapid the original growth the more rapid was the
      following destruction. In this series of experiments, which were performed early
      in 1929, although the delayed destruction of the bovine type in the rabbit was
      amply confirmed, the original rate of growth is not any slower than the human
      type. Coincident with this increasingly more rapid rate of growth of the bovine
      bacillus in the body is a gradual decrease in the virulence of the organism. In
      1925 and 1926 0.01 mg. of this bovine strain regularly killed rabbits in about 30
      days after intravenous inoculation (8), but in this experiment none of the 3
      rabbits died within 65 days after a similar infection and 2 rabbits were still
      living 110 days after injection.

PMID- 19869662
TI  - STUDIES ON THE DISSOCIATION OF THE HOG CHOLERA BACILLUS : III. ACTIVE
      IMMUNIZATION WITH R FORMS.
AB  - 1. Heat killed organisms of the MS (OH), MR (OH), NS (O) or NR (O) forms of hog
      cholera bacilli failed to confer immunity, at least to any considerable degree,
      in hamsters or rabbits against virulent hog cholera bacilli. 2. Hamsters and
      rabbits were successfully immunized against virulent MS bacilli by vaccination
      with living MR (OH) and NR (O) forms. 3. Hamsters were immunized against MS hog
      cholera bacilli with living R paratyphoid "C" bacilli and conversely against MS
      paratyphoid "C" bacilli with living R hog cholera bacilli.

PMID- 19869663
TI  - ANAPHYLACTIC SHOCK WITH THE PARTIAL ANTIGEN OF THE TUBERCLE BACILLUS.
AB  - 1. Typical lethal anaphylactic shock has been produced in guinea pigs by means of
      the specific carbohydrate derived from a human strain of tubercle bacillus. The
      phenomenon has been observed in animals both actively and passively sensitized.
      2. Typical contractions have been evoked in the isolated uterus of guinea pigs
      upon the addition of the specific carbohydrate to the bath. 3. True anaphylactic
      shock against the specific carbohydrate in guinea pigs sensitized with the
      tubercle bacillus does not prevent or diminish the cutaneous reaction to O. T. in
      those animals which recover.

PMID- 19869664
TI  - SENSITIVITY TO METHYLENE BLUE AND FINAL ACIDITY OF NON-HEMOLYTIC STREPTOCOCCI.
AB  - The results of the present study may be briefly summarized as follows. Acid
      production and sensitivity to methylene blue of 55 strains of methemoglobin
      forming streptococci from various sources were studied to determine whether it is
      possible on the basis of these reactions to differentiate strains of human,
      bovine, and dairy origin. Twelve strains were isolated from human infections, 6
      from bovine mastitis, and 37 from dairy products. The final hydrogen ion
      concentrations of all cultures in dextrose broth regardless of the sources from
      which the strains originated, covered the range pH 5.2 to 4.1. There appeared,
      therefore, to be no correlation between the amount of acid produced by a given
      strain and the source from which it was originally derived. Low acid production,
      a characteristic of hemolytic streptococci of the human type, was not a
      distinguishing mark of the green producing organisms from human infection, and
      high acid production was not limited to strains from bovine and dairy sources.
      Differences between saprophytic and parasitic strains in their sensitivity to
      methylene blue in milk were not so sharply defined as were those previously
      demonstrated for the hemolytic streptococci. Of 18 strains of human and bovine
      infections, 14 showed neither reduction nor growth in the presence of a 1.5000
      concentration of methylene blue. Of the 38 strains from dairy products 32 reduced
      the dye and grew in this concentration. The results with the non-hemolytic
      streptococci indicate that the saprophytic strains have a greater tolerance for
      the dye than have the strains of parasitic origin. The significance of these
      results in the differentiation of streptococci of human, bovine and dairy origin
      is discussed.

PMID- 19869665
TI  - STUDIES ON YELLOW FEVER IN SOUTH AMERICA : IV. TRANSMISSION EXPERIMENTS WITH
      AEDES AEGYPTI.
AB  - 1. Batches of Aedes (Stegomyia) aegypti which had fed on monkeys in the early
      febrile stage of yellow fever and which has subsequently passed the usually
      accepted extrinsic incubation period for the virus, failed to transmit the
      disease to normal monkeys in approximately fifty per cent of the experiments.
      During the same time over eighty per cent of blood transfers were successful. 2.
      The monkeys which failed to show fever following mosquito bites later proved
      resistant to the inoculation of blood or tissues containing virus. 3. The
      incubation, or afebrile, period in monkeys following the bites of infected
      mosquitoes varied from less than twenty-four hours to fifteen days. It averaged
      somewhat longer in non-fatal than in fatal infections.

PMID- 19869666
TI  - STUDIES ON YELLOW FEVER IN SOUTH AMERICA : V. TRANSMISSION EXPERIMENTS WITH
      CERTAIN SPECIES OF CULEX AND AEDES.
AB  - 1. Yellow fever virus has been transmitted from monkey to monkey both by the
      bites of Aedes (Ochlerotatus) scapularis which had fed upon monkeys infected with
      yellow fever and by the injection of the ground up bodies of such mosquitoes. 2.
      A fatal infection has been obtained by the injection of the ground up bodies of
      Aedes (Ochlerotatus) serratus, which had previously fed on an infected monkey,
      and a mild infection has been secured by the similar injection of Aedes
      (Taeniorhynchus) taeniorhynchus. 3. No definite infection has been secured either
      by the bites or by the injection of Culex quinquefasciatus (C. fatigans).
      However, some of the experimental animals bitten by this species have been
      relatively immune following inoculations of blood or tissues containing virus.

PMID- 19869667
TI  - A QUANTITATIVE STUDY OF THE PRECIPITIN REACTION BETWEEN TYPE III PNEUMOCOCCUS
      POLYSACCHARIDE AND PURIFIED HOMOLOGOUS ANTIBODY.
AB  - 1. A quantitative study of the reaction between the soluble specific substance of
      Type III pneumococcus and its homologous antibody has been made. 2. The entire
      reaction, from excess of antibody, to excess of specific substance with its
      accompanying inhibition zone effect, may be expressed by three mass-law
      equations. 3. The significance of these findings is discussed.

PMID- 19869668
TI  - STUDIES IN AGGLUTINATION : IV. THE AGGLUTINATION INHIBITION ZONE.
AB  - 1. The agglutination inhibition zone, artificially produced by heating, has been
      studied. 2. The phenomenon is specific and is dependent upon the presence in the
      inhibition zone serum of altered agglutinin (agglutinoid).

PMID- 19869669
TI  - INTRADERMAL IMMUNIZATION OF MONKEYS WITH ONE SET OF INJECTIONS OF POLIOMYELITIS
      VIRUS.
AB  - 1. By means of a single large dose of poliomyelitis virus, distributed at a
      number of intradermal sites, active immunity has been produced in Macacus rhesus
      monkeys, as shown by skin neutralization and intracisternal tests. 2. In the
      small series (four animals) of monkeys so treated, neither abortive nor paralytic
      signs of experimental poliomyelitis appeared.

PMID- 19869670
TI  - THE TRANSFORMATION OF PNEUMOCOCCAL TYPES : II. THE INTERCONVERTIBILITY OF TYPE
      SPECIFIC S PNEUMOCOCCI.
AB  - 1. Type-specific S pneumococci may be transformed from one specific S type into
      other specific S types through the intermediate stage of the R form. 2. R forms
      of pneumococi, derived from any specific S type, may be transformed into S
      organisms of other specific types by the following procedure:-The subcutaneous
      injection, in white mice, of small amounts of living R forms together with
      vaccines of heterologous S cultures. (i) S vaccines heated for 15' at
      temperatures between 60 degrees and 80 degrees C., are effective in causing R
      forms, derived from heterologous S types, to revert to the type of the vaccine.
      (ii) S vaccines heated for 15' at temperatures between 80 degrees and 100 degrees
      C., are not effective in causing R forms, derived from heterologous S types, to
      revert to the type of the vaccine. (iii) S vaccines heated for 15' at
      temperatures between 80 degrees and 100 degrees C., may cause 2 R and 3 R
      cultures to revert to their original S type. (iv) S vaccines of any type,
      including Type I, heated for 15' at temperatures between 80 degrees and 100
      degrees C., are not effective in causing 1 R cultures to revert to their original
      S type. (v) S vaccines heated for periods as long as two hours at 60 degrees C.
      are effective in causing R forms, derived from heterologous types, to revert to
      the type of the vaccine. 3. A single cell R strain, derived from a Type II S
      pneumococcus, has been successively transformed into a Type III S, a Type I S and
      a Group IV S culture. 4. Corresponding with the various degrees of "degradation"
      of the R form there are varying degrees of "development" of the S form. 5. The
      nature of the conditions responsible for alteration of type as induced by these
      procedures has been investigated and the causes responsible for the
      transformations are discussed. 6. All attempts to produce transformation of type
      in vitro have been unsuccessful. 7. The ro1e which the phenomenon of
      transformation of type may play in problems of infection and epidemiology is
      indicated.

PMID- 19869671
TI  - SURVIVAL OF VACCINE VIRUS SEPARATED FROM LIVING HOST CELLS BY COLLODION
      MEMBRANES.
AB  - Vaccine virus, suspended in a mixture of serum and Tyrode's solution and
      separated by collodion membranes from a suspension of living kidney cells in
      serum and Tyrode's solution, remained active at 37 degrees C. for a longer period
      of time than did vaccine virus incubated only in a mixture of serum and Tyrode
      solution.

PMID- 19869672
TI  - THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : VII. THE EFFECT OF
      LOCAL AND SYSTEMIC BLOCKADE ON THE TOXIC ACTION OF HETEROPHILE (FORSSMAN) SERA IN
      GUINEA PIGS.
AB  - 1. Guinea pigs blocked by intravenous injection of either India ink or trypan
      blue succumbed with fatal shock after the intravenous injection of heterophile
      immune serum, although the time of death was somewhat delayed as compared with
      normal controls. 2. Local blockade of the skin of guinea pigs with trypan blue
      inhibited completely the development of the characteristic skin reaction
      following intracutaneous injection of Forssman serum within the blocked area. 3.
      Infiltration of the skin of guinea pigs with India ink afforded no protection
      against the full development of the toxic skin reaction.

PMID- 19869673
TI  - A COMPARISON OF THE METHOD OF EXCRETION OF NEUTRAL RED AND PHENOL RED BY THE
      MAMMALIAN KIDNEY.
AB  - A direct examination with the method of perfusion of the excretion by the frog's
      kidney of phenol red and neutral red has shown that the dyes are eliminated in
      different manners as a result of different mechanisms. The former is excreted in
      much the greater part by the glomeruli; the latter by the tubules. Urea is
      excreted in a manner similar to phenol red. The indirect examination of the
      function of the mammalian kidney by means of excretion ratios has shown a like
      contrast between the manner of elimination of the two dyes, and here again was
      found a similarity in the manner of excretion of phenol red and urea. This would
      seem to be as close an examination as can be made with our present methods of
      experimentation of the question of the mechanism of the excretion of these
      substances by mammals. As the facts stand they constitute strong presumptive
      evidence that in mammals and amphibia the like results have arisen from like
      causes, phenol red and urea being eliminated chiefly through the glomeruli in
      both instances while neutral red is excreted principally through the tubules.

PMID- 19869674
TI  - THE EFFECT OF THE X-RAY ON THE NODULES OF VERRUGA PERUANA.
AB  - The supposition that X-ray would affect the developing and the developed verruga
      nodules experimentally induced in the monkey, has proved correct. The experiments
      show that the early verruga nodules when exposed to a single, properly graduated
      dose of X-ray producing merely erythema of the skin, are inhibited in their
      evolution. Moreover, the skin of Macacus rhesus monkeys is modified by a single
      erythema dose of X-ray in such a way that infection of it with Bartonella
      bacilliformis is rendered more difficult. These results are sufficiently striking
      to warrant the trial of X-ray in suitably guarded doses in the treatment of
      verruga nodules in man. Should the employment of convalescent serum influence the
      course of Carrion's disease favorably and the use of X-ray bring about a more
      certain and rapid devolution of verruga nodules in man, two practically
      applicable therapeutic measures will have been provided for the treatment of the
      two forms of the human disease.

PMID- 19869675
TI  - IS THE LOCAL VASODILATATION AFTER DIFFERENT TISSUE INJURIES REFERABLE TO A SINGLE
      CAUSE?
AB  - Experiment shows that the vascular contraction responsible for Bier's spotting
      prevails over the local vasodilatation due to mechanical injury of the skin, and
      causes the local reddening to blanch. It is without effect, however, upon the
      local vasodilatation caused by histamine pricked into the skin. The results raise
      doubts concerning the validity of the hypothesis referring all local
      vasodilatations to the action of a single chemical substance or set of substances
      ("H substance"), liberated within the tissues.

PMID- 19869676
TI  - AN APPARATUS FOR THE STUDY OF RESPIRATORY QUOTIENT AND BASAL METABOLISM OF MICE.
AB  - A simple apparatus has been developed for the study of the respiratory quotient
      and basal metabolism of mice. Data are given which indicate that the values for
      the respiratory quotient obtained are accurate to within 0.02. The apparatus is
      especially designed for rapid, routine manipulation.

PMID- 19869677
TI  - THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : VI. THE EFFECT OF
      ENDOTHELIAL BLOCKADE ON THE STORAGE AND DISTRIBUTION OF NEOARSPHENAMINE.
AB  - 1. Blockade of the reticulo-endothelial system by means of a single injection of
      India ink caused a marked retention of neoarsphenamine in the blood of guinea
      pigs during the first twenty minutes of observation after intravenous injection,
      as contrasted with the rapid disappearance of the drug from the blood of normal
      controls. 2. Rabbits blocked by a single dose of India ink showed a slower
      elimination of the drug from the circulation following the first few hours after
      intravenous injection than corresponding controls. 3. The arsenic content of the
      liver of mice, which received neoarsphenamine intravenously after a preceding
      blocking injection with India ink, was appreciably lower than the arsenic content
      of the normal organ under similar experimental conditions.

PMID- 19869678
TI  - THE EFFECT OF UNILATERAL NEPHRECTOMY ON THE SENILE ATROPHY OF THE KIDNEY IN THE
      WHITE RAT.
AB  - 1. In senility in the white rat there is a decrease in the total number of
      glomerular units. 2, The decrease in glomerular units is associated with an
      increase in the average diameter and a greater variation in size, of the
      remaining glomeruli. 3. Unilateral nephrectomy during adult life has no effect on
      these senile changes.

PMID- 19869679
TI  - ON THE ISOLATION, CULTIVATION AND CLASSIFICATION OF THE SO-CALLED INTRACELLULAR
      "SYMBIONT" OR "RICKETTSIA" OF PERIPLANETA AMERICANA.
AB  - In Periplaneta americana, the large American roach, bacteriocytes are found in
      both sexes. These bacteriocytes are scattered throughout the fat tissue and their
      cytoplasm is filled with microorganisms. Evidence is presented to show that the
      intracellular forms are diphtheroidal bacilli. These diphtheroids are transmitted
      from one generation to another through the ova. A method is described whereby
      tissues, free from contaminants, may be obtained from Periplaneta. A medium and a
      new method, the "spotting technique," are described, by means of which initial
      cultures of the parasites were obtained from eggs within capsules, from ova and
      fat tissue bacteriocytes. Two conditions appear necessary, one to initiate
      adaptation to the new environment, the other to bring its complete realization to
      fruition. When development has been properly initiated, further adaptation occurs
      with successive transfers until finally certain other media appear suitable.
      Approximately 14 per cent of the isolation and cultivation attempts succeeded.
      All of the isolations were studied and it was found that three morphologically
      distinct types had been cultivated. In general one host yielded only one type,
      but one female revealed three types and another two. One type was also isolated
      once from a fecal emulsion. The probable reason for this result is discussed. The
      three types isolated were diphtheroidal bacilli resembling one another closely
      enough to be considered a single species but invariably offering distinct minor
      differences to warrant a separation into three distinct types. These three types
      have remained true to their original forms and sizes through 52 transfers. The
      sizes, general morphology, and tinctorial reactions of the three types cultivated
      correspond to the intracellular parasites of Periplaneta americana. The cultural
      and biochemical activities of the strains did not reveal any sound characters for
      differentiating types. Serologically, however, useful distinctions were found.
      Some additional evidence along immunological lines is offered to show that the
      microorganism cultivated is a representative of the identical species parasitic
      within Periplaneta americana. The evidence appears sound to the writer that the
      Periplaneta parasite has been isolated and cultivated over 20 times and that it
      is a bacterium belonging to the genus Corynebacterium (the diphtheroids). For the
      species the name Corynebacterium periplanetae nov. sp. variety americana is
      proposed. The three cultural types did not produce forms small enough to pass
      through the pores of Berkefeld "N" candles.

PMID- 19869680
TI  - STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : I. BLOOD COUNTS IN NORMAL RABBITS.
AB  - A study of the blood cytology of normal male rabbits was carried out from October
      20, 1927 to November 22, 1928 in connection with an investigation of
      constitutional and environmental factors related to the occurrence and course of
      disease. In 1110 observations on 174 animals, total red and white cells counts,
      differential white cell counts by the supravital method, and hemoglobin
      estimations were made. A statistical analysis of the results obtained is
      presented. Attention is directed to the occurrence of wide variations in the
      numbers of the various white cells as contrasted with comparatively small
      variations in the numbers of red cells and of hemoglobin content. The results
      recorded are regarded as representing approximate rather than fixed values of
      normality.

PMID- 19869681
TI  - THE TRANSFORMATION OF PNEUMOCOCCAL TYPES : I. THE CONVERSION OF R FORMS OF
      PNEUMOCOCCUS INTO S FORMS OF THE HOMOLOGOUS TYPE.
AB  - R forms of Pneumococcus may be converted into S forms of the homologous Type. In
      addition to the methods previously reported,-(1) animal passage and (2) growth in
      anti-R sera,-conversion may be effected by the following procedures as employed
      by Griffith; (1) The subcutaneous injection, in white mice, of large amounts of
      living R organisms. (2) The subcutaneous injection, in white mice, of small
      amounts of living R organisms together with the heat-killed bacteria from large
      amounts of homologous S cultures. There are "varying degrees of constancy of the
      R variant"; but by these means it has been possible to effect conversion of all R
      forms selected. Attempts to cause a further "degradation" of R organisms by
      continued growth in homologous immune serum have been unsuccessful. Type II S and
      III S vaccines are equally effective in producing conversion when heated for 15'
      at 60 degrees C., or for 15' at 100 degrees C. Type I S vaccine, however, while
      effective in causing conversion when heated for 15' at 60 degrees C., apparently
      loses this property when heated for 15' at 100 degrees C. R vaccines, and
      vaccines of other organisms, when injected together with live R cultures, have
      always failed to produce conversion. The causes responsible for conversion under
      these experimental conditions are discussed and the possibility of the occurrence
      of a similar process under natural conditions in human beings is indicated.

PMID- 19869682
TI  - VARIATIONS IN THE PLASMA CHOLESTEROL AND CHOLESTEROL ESTER CONTENT IN HOG
      CHOLERA.
AB  - 1. The plasma cholesterol and cholesterol ester content of swine, experimentally
      infected with hog cholera, exhibit a regular succession of changes. During the
      period of incubation of the disease, for 3 or more days following inoculation
      with hog cholera virus, hypocholesterolemia prevails. This is followed by a
      period of hypercholesterolemia which is coincident with the onset of the clinical
      manifestations of the disease. The hypercholesterolemia after persisting for from
      4 to 7 days, gives way to a second period of hypocholesterolemia more marked and
      more prolonged than that observed immediately after inoculation. In the
      experiments of the present work this second period lasted 8 and 11 days in the 2
      animals surviving long enough for the study of it and was followed by a second
      period of hypercholesterolemia. In the one animal surviving this period for 8
      days a third period of irregular and fluctuating hypocholesterolemia set in. 2. A
      comparison with the results in other acute infections indicates that hog cholera
      is unique in showing alternating periods of hypocholesterolemia and
      hypercholesterolemia. 3. A normal hog inoculated with Bacillus suisepticus
      rapidly developed the typical marked hypocholesterolemia whereas an animal
      infected with hog cholera and then inoculated with B. suisepticus failed to show
      the decrease in plasma cholesterol content.

PMID- 19869683
TI  - ON THE RELATION OF THE ORGANISMS IN THE TUNICA VAGINALIS OF ANIMALS INOCULATED
      WITH MEXICAN TYPHUS TO RICKETTSIA PROWAZEKI AND TO THE CAUSATIVE AGENT OF THAT
      DISEASE.
AB  - Healthy lice became infected with Rickettsia prowazeki after feeding on monkeys
      inoculated with a strain of Mexican typhus. The same result was obtained in 100
      per cent of lice by rectal inoculation of an emulsion of tunica vaginalis of
      guinea pigs reacting to the same strain. In the tunica vaginalis of guinea pigs
      and rats inoculated intraperitoneally with an emulsion of lice containing
      Rickettsia prowazeki the intracellular organism constantly associated with the
      passage strain appeared regularly. Rickettsia prowazeki found in lice and the
      organism constantly present in the tunica of guinea pigs and rats reacting to our
      strain of tabardillo are indistinguishable morphologically and tinctorially and
      their mode of intracellular multiplication is alike in every respect. It is
      concluded that they are identical. This organism is constantly associated with
      the causative agent of Mexican typhus, both in mammals and in lice, and all of
      our attempts to separate them have failed.

PMID- 19869684
TI  - THE RECOVERY OF VACCINE VIRUS AFTER NEUTRALIZATION WITH IMMUNE SERUM.
AB  - 1. When vaccine virus and its specific antiserum are brought together, no
      evidence of stable union between them can be determined by the experimental
      methods employed. 2. A definite relationship exists between the degree of
      dilution of a neutral vaccine virus-antiserum mixture and the size of the lesion
      produced by endermic inoculation of rabbits of any given dilution.

PMID- 19869685
TI  - THE EPIDEMIOLOGY OF FOWL CHOLERA : EXPERIMENTAL STUDIES I. INTRODUCTION.

PMID- 19869686
TI  - THE EPIDEMIOLOGY OF FOWL CHOLERA : II. BIOLOGICAL PROPERTIES OF P. AVICIDA.
AB  - 1. A bacteriological study has been made of 210 fresh strains of Pasteurella
      obtained from typical cases of fowl cholera on seven widely separated poultry
      farms. 2. The strains have proved identical in consisting of small, pleomorphic,
      bipolar staining, Gram-negative, non-motile bacilli. They grew rapidly in
      infusion broth plus a trace of hemolgobin. They formed acid but no gas in media
      containing dextrose, saccharose, and mannite; indol was produced. 3. The strains
      fall into three distinct groups, according to their colony formation on
      hemoglobin agar. The "fluorescent" colony was large, whitish, opaque, exhibiting,
      under suitable conditions marked fluorescence. The "blue" colony was smaller,
      clear slate-blue, and non-fluorescent. The "intermediate" colony was moderately
      fluorescent at 15-18 hours growth, and "blue" thereafter. It was "blue" at all
      times when crowded and occasionally of "ring" form. "Fluorescent" colony cultures
      developed "blue" colony forms under certain conditions; otherwise all forms were
      stable. 4. Strains from "fluorescent" colonies were resistant to precipitation by
      acids, to sedimentation by centrifuging, and although they combined with specific
      antiserum, did not agglutinate. They were relatively highly virulent and occurred
      in flocks where fowl cholera was epidemic. 5. Strains from "blue" colonies were
      precipitated by acids over a wide range of concentration and agglutinated
      strongly in antisera. They were relatively of low virulence and occurred in
      flocks where fowl cholera was endemic. 6. Strains from "intermediate" colonies
      varied in behavior betweee the "fluorescent" and "blue" strains. They came from a
      flock where fowl cholera was epidemic.

PMID- 19869687
TI  - THE EPIDEMIOLOGY OF FOWL CHOLERA : III. PORTAL OF ENTRY OF P. AVICIDA; REACTION
      OF THE HOST.
AB  - 1. In the experiments here presented, P. avicida proved incapable of inciting
      fowl cholera when introduced directly into the alimentary tract. On the other
      hand, when administered into the upper respiratory passages, it induced typical
      disease. 2. When P. avicida was introduced into the nasal passages of controlled,
      selected chickens, some died of typical septicemic cholera, a few developed
      chronic pneumonias and other conditions and succumbed, a few developed localized
      upper respiratory inflammations, such as rhinitis, roup, and wattle involvement,
      while yet a few others became "healthy" nasal carriers. Usually, however, more
      than 50 per cent resisted infection. Repeated titrations of this sort gave, in
      general, uniform results, save that in spring and summer the per cent mortality
      decreased. 3. P. avicida was recovered from a number of cases of "spontaneous"
      roup, rhinitis, and wattle disease. 4. Groups of chickens reacted similarly to
      doses of virulent P. avicida varying from 20,000,000 to 20,000. Outside these
      limits, dosage exercised a marked influence on mortality.

PMID- 19869688
TI  - THE EPIDEMIOLOGY OF FOWL CHOLERA : IV. FIELD OBSERVATIONS OF THE "SPONTANEOUS"
      DISEASE.
AB  - Field studies of fowl cholera on two commercial poultry farms are described. One
      farm, previously free of cholera, was studied during an active epidemic, which
      occurred during the winter months. The strains of P. avicida recovered, both from
      "autopsy" and from "healthy carriers" proved generally similar, and to be of the
      "fluorescent" or "intermediate" colony type, which is of relatively high
      virulence. After the subsidence of the epidemic, these strains tended to
      disappear. The second flock consisted of a small group of birds which had
      survived an epidemic of cholera the previous year, and in which the infection was
      prevailing in endemic form. No deaths occurred during the period of observation,
      but the number of birds with localized lesions and the number of carriers
      increased to a high level during the winter months. The strains of P. avicida
      were apparently of the "blue" colony form, although some, as shown by their acid
      and serum agglutination reactions, resembled the "intermediates." These strains
      appeared to be spreading rather than dying out. The individual fowls differed in
      their response to the presence of infection; some showed localized lesions,
      others were carriers, while still others seemed entirely refractory.

PMID- 19869689
TI  - THE EPIDEMIOLOGY OF FOWL CHOLERA : V. FURTHER FIELD OBSERVATIONS OF THE
      SPONTANEOUS DISEASE.
AB  - An investigation of endemic fowl cholera, the common form of the disease in this
      locality, has been made at a poultry farm in Belle Meade, N. J. The focus or
      reservoir of P. avicida proved to be the healthy pullets which had become
      carriers the previous year and which were selected as the breeding stock for the
      ensuing season. From these carriers, the organisms spread and gave rise during
      the winter months to the various forms of infection, including the carrier state,
      localized upper respiratory disease, and typical cholera. Strains of P. avicida
      were in general very similar and of the "blue" colony type. They were all of the
      same low degree of virulence; no differences were demonstrable between a)
      "carrier" and "autopsy" strains, b) strains where the infection was spreading and
      severe, and strains where disease was rare, and c) "autumn" and "winter" strains.
      In general, a relatively high carrier rate was accompanied by a high mortality
      rate, although in one instance, a community with high carrier incidence plus a
      probable high degree of host resistance suffered but little fatal infection. An
      attempt was made to reduce the amount of cholera by the removal of carriers. The
      results of this measure indicate that such a procedure is both effective and
      practical.

PMID- 19869690
TI  - EARLY PULMONARY LESIONS IN PARTIALLY IMMUNE ALCOHOLIZED MICE FOLLOWING INHALATION
      OF VIRULENT PNEUMOCOCCI.
AB  - 1. The serial section examination of 71 partially immune alcoholised mice which
      were killed at intervals following the inhalation of virulent pneumococci showed
      pulmonary localisation in 7 or 9%. 2. In the case of the mouse the initial lesion
      of pneumococcus pneumonia is in the alveolar wall and the exudate into the
      alveolar lumen occurs secondarily.

PMID- 19869691
TI  - STUDIES ON INFLAMMATION : II. A MEASURE OF THE PERMEABILITY OF CAPILLARIES IN AN
      INFLAMED AREA.
AB  - 1. By means of a colorimetric method the concentration of trypan blue in
      capillaries can be estimated by direct observation and its changes followed as
      the dye passes out of the circulating blood stream. 2. The change in
      concentration of trypan blue in the capillaries of both the normal and the
      inflamed mesentery of frogs can be described by two separate exponential
      equations of the type: y = be(-ax). 3. From these equations it is found that the
      rate of fall of concentration following intraventricular injection of the dye is
      almost twice as great in the capillaries of the inflamed as in those of the
      normal mesentery. This difference is a measure of increased permeability with
      inflammation.

PMID- 19869692
TI  - THE IMMUNOLOGICAL SPECIFICITY OF CHEMICALLY ALTERED PROTEINS : HALOGENATED AND
      NITRATED PROTEINS.
AB  - The serological properties of iodoproteins prepared by a method which involves
      less drastic treatment of the protein than the methods previously used for this
      purpose confirm the findings of Obermayer and Pick (1) and later authors, that
      iodination of proteins results in a more or less complete loss of species
      specificity and that a new specificity characteristic for iodoproteins is
      produced. A serological investigation of brominated proteins has been made for
      the first time. These preparations are only slightly different from iodized
      proteins in their serological properties. Evidence is submitted which indicates
      that the radical in iodoproteins which is responsible for the specificity is not
      iodine but the 3:5 dihalogenated tyrosine grouping. Thus marked inhibition of the
      iodoprotein (or bromoprotein) precipitin reactions is effected by 3:5
      dihalogenated tyrosine, not by iodophenol or potassium iodide. A reinvestigation
      has been made of the serological properties of nitrated and diazotized proteins.
      Proteins nitrated by nitric acid, or by a method which does not appear to have
      been used for proteins hitherto, namely nitration with tetranitromethane in
      neutral or slightly alkaline solution, acquire a new common serological
      specificity. The nitrated proteins and diazotized proteins show, in confirmation
      of the results of Landsteiner and Prasek (22) and in contrast to the findings of
      Obermayer and Pick, very little difference in their reactions. Thus diazotized
      proteins and proteins nitrated by either of the two methods above mentioned react
      equally well with any nitroprotein antiserum. This interaction exists in spite of
      the difference in the substituents, either because the substitution with the
      nitro- or diazo-group occurs in the same position in the aromatic nucleus,
      possibly in the ortho position to the hydroxyl group, or because of some other
      structural similarity. In the last connection it is suggested that both compounds
      may have a quinoid structure as has been assumed for ortho-nitrophenols. Whilst
      this assumption could account for the marked serological difference of nitrated
      and halogenated proteins it should also be mentioned that iodination (and
      bromination) lead to a disubstitution of halogen in the two ortho positions
      relative to the hydroxyl group of the tyrosine whereas nitration of proteins
      probably results in the formation of mononitrotyrosine and substitution in the
      tryptophane group as well (19, 36, 20-a). It is probably impossible therefore, to
      draw a strict analogy between nitration (or diazotization) and halogenation of
      proteins since a comparison of their immunological properties is not exactly a
      comparison of the effect of substituting a different group in the same position.
      Accordingly it would appear that as yet no definite conclusions can be drawn as
      to the serological effect of differences in the chemical nature of various
      substituents in the aromatic nucleus although some influence is likely for
      general reasons. All of the chemically altered proteins still retain a small
      amount of the original species specificity, and the antisera always react to a
      slightly greater extent with the homologous antigen than with similarly treated
      antigens prepared from heterologous sera. This difference occurs even when the
      possibility of some unaltered protein being present in the antigen can be
      practically excluded.

PMID- 19869693
TI  - A CONCENTRATING DIALYZER.
AB  - An apparatus is described for dialyzing aqueous solutions and simultaneously
      concentrating them to a thick syrup, or even to dryness. The fluid is placed in
      collodion bags with reservoir bulbs open to atmospheric pressure. The bags are
      surrounded by flowing cold water, under negative pressure, and are subjected of a
      rocking motion. Over a liter of fluid can be concentrated to a few cubic
      centimeters in 3 to 4 hours. It is kept cold and sterile during the process.

PMID- 19869694
TI  - THE BACTERIAL GROWTH INHIBITOR (LACTENIN) OF MILK : I. THE PREPARATION IN
      CONCENTRATED FORM.
AB  - The bacterial growth inhibitory substance found in milk is called lactenin in
      this paper. It is stable for 1(1/2) hours at pH 4 and at pH 10 and for longer
      periods in neutral solution. It is not associated with salts and carbohydrates
      and may be separated from them by dialysis. Lactenin is removed by agents which
      precipitate the proteins of whey. Part of these proteins may be hydrolyzed by
      tryptic digestion and the resulting split products, together with the salts and
      sugar, may then be removed by dialysis without appreciable loss of lactenic
      activity. This dialysis may be performed in a concentrating dialyzer, under
      sterile conditions and at low temperature, thus reducing the solution to small
      volume. The material may then be completely desiccated and kept 3 months with
      practically no loss of activity. The residue, on treating this dried material
      with salt solution, is 200 times as active as the original milk, on a dry weight
      basis. The size of hemolytic zones of the scarlet fever streptococcus grown on a
      medium containing lactenin is found to furnish a simple and reliable measure of
      lactenic activity.

PMID- 19869695
TI  - CHEMOTHERAPEUTIC EQUILIBRIA.
AB  - 1. The general adequacy of the bacteriostatic mechanism for the action of dyes
      which postulates a mass law equilibrium between bacteriostat and organism, which
      latter is pictured chemically as an ampholyte, is discussed. 2. It is shown that,
      even in blood, where, with safe concentrations of dye, there seems to be a
      significant excess of protein over dye, the stoichiometric excess of dye required
      by the above mechanism is available. 3. Experiments are presented indicating that
      the time required for such a bacteriostat to act is very short, being probably
      conditioned largely by speed of mixing or of penetration. 4. Apparent
      disappearance of dye from blood stream need not mean that the blood has lost
      bacteriostatic value. 5. Data are presented indicating that the behavior of dyes
      in causing flocculation of organisms is affected by the same factors and in the
      same way as in inhibiting growth. 6. Direct evidence of ionic combination between
      dye ion and protein ion is presented by noting conductivity decrease when the two
      ions are mixed, and also noting the displacement of H-ion from unionized protein
      by dye cation, or of OH-ion by dye anion.

PMID- 19869696
TI  - THE REFRACTORY PERIOD OF THE NORMALLY-BEATING DOG'S AURICLE; WITH A NOTE ON THE
      OCCURRENCE OF AURICULAR FIBRILLATION FOLLOWING A SINGLE STIMULUS.
AB  - 1. A method is described for determining the refractory period of the dog's
      auricle during the normal sinus rhythm. The advantages of the method are: (a) The
      total stimulating effects of repeated induction shocks are avoided. (b) The
      action current is recorded from a point one millimeter or less from the point of
      stimulation. (c) Alterations in the spontaneous rate of the auricle do not
      interfere with the accurate determination of the refractory period. 2. The values
      obtained for the normal refractory period and the changes produced by atropine
      and by stimulation of the vagus agree closely with those of previous observers.
      3. The automatic features of the method make possible the determination of the
      refractory period under adrenalin. This drug brings about a distinct shortening
      of the refractory period but less than that produced by stimulation of the vagus.
      4. During vagal stimulation a single induction shock, introduced soon after the
      end of the refractory period, frequently produces auricular fibrillation. The
      cause of this irregularity is discussed and its relation to clinical auricular
      fibrillation is suggested.

PMID- 19869697
TI  - STUDIES ON VITAL STAINING : I. SOME PROBLEMS IN COLORIMETRY. THE QUANTITATIVE
      ANALYSIS OF MIXTURES OF COLORED SUBSTANCES IN SOLUTION.
AB  - 1. A spectrophotometric method is discussed which permits quantitative analysis
      of colored substances present in mixtures. 2. Special attention is given to the
      analysis of mixtures of two dyes which are being used in a series of studies on
      vital staining. 3. It is shown that the method can be applied to quantitative
      analysis of mixtures of naturally occurring animal pigments or to mixtures of
      these with various other colored substances. 4. Certain limitations of the method
      and certain necessary precautions are discussed.

PMID- 19869698
TI  - STUDIES ON VITAL STAINING : II. THE REMOVAL OF BRILLIANT VITAL RED FROM THE BLOOD
      STREAM. DISTRIBUTION OF DYE BETWEEN BLOOD STREAM AND BODY TISSUES.
AB  - Brilliant vital red injected into the blood stream of dogs is slowly taken up by
      phagocytes in various parts of the body, but eventually an equilibrium is
      established, after which the concentration as measured in the plasma remains
      almost constant for long intervals of time. This equilibrium can be disturbed by
      injecting more dye, and in this case the phagocytes resume ingestive activity,
      apparently with normal or nearly normal vigor. This activity continued until a
      rather large part of the newly injected dye has been removed, and as the reaction
      again slows up we note that both plasma and tissues contain more dye than before.
      It is difficult to be certain that the distribution ratio of dye between plasma
      and tissues remains unaltered with dosage, but evidence indicates that for non
      toxic doses, at least, this is approximately true. This study of this partition
      ratio is complicated by the fact that the liver slowly excretes dye into the
      bile, and this helps to reduce the amount of dye in the body. Partial correction
      for this factor can be made by ascertaining the dye output in bile fistula dogs.
      These latter studies show that dye elimination into bile is relatively less
      efficient when large doses of dye are given to the animal than with smaller
      dosage. This undue retention of dye in the body with large dosage helps to
      maintain the dye concentration in the plasma at unduly high levels. These
      peculiarities in liver excretion have an important bearing on liver physiology in
      general, and in addition they also have an important application in connection
      with the theory of "blockade of the reticulo-endothelial system." It is now
      obvious that prolonged retention of dye in the blood stream does not of itself
      prove that this group of phagocytic cells is "blocked" against the entrance of
      foreign material. Altered excretion by liver, kidney, etc. must be ruled out
      before we can accept such data as evidence of "blockade."

PMID- 19869699
TI  - STUDIES ON VITAL STAINING : III. THE SIMULTANEOUS INGESTION OF TWO DYESTUFFS BY
      PHAGOCYTES. THE QUESTION OF "BLOCKADE OF THE RETICULO-ENDOTHELIAL SYSTEM".
AB  - When large amounts of brilliant vital red are injected into the blood stream of
      dogs, the dye is gradually removed from circulation, and most of it is deposited
      in numerous phagocytic cells which are scattered throughout various organs and
      tissues. The dye occurs largely in the form of tiny red granules crowded together
      in the cytoplasm of these cells. If Niagara sky blue, a closely related dyestuff,
      is injected, it too is taken up and stored in these same cells. It is shown that
      the presence of red dye in the tissues does not inhibit the cells from taking up
      the blue one. The normal ability of the phagocytes to take up Niagara sky blue is
      observed also when this dye is injected simultaneously with brilliant vital red.
      This normal response toward the blue dye is seen even though the phagocytes are
      busied at the same time in the process of engulfing and storing the red dye.
      These experiments show that it is difficult if not impossible to "block" the
      cells with one dye so that their ability to take up another is even slightly
      impaired. The two dyes employed in these studies are shown to be particularly
      suitable for experiments of the sort here reported.

PMID- 19869700
TI  - CUTANEOUS REACTIONS WITH CULTURE FILTRATES OF THE COLON TYPHOID TYPE.
AB  - The observations of Ecker and Rimington on the production of skin reactions with
      synthetic medium culture filtrates (concentrated and dialyzed) of organisms
      belonging to the colon-typhoid group have been confirmed and extended. The
      filtrates show a marked degree of thermostability and marked resistance to
      ultraviolet radiation. Intravenous injections of the filtrates stimulate the
      production of precipitins. No precipitins are produced in the sera of rabbits
      that receive intracutaneous injections only. At no time during the course of
      immunization was the skin reaction obliterated. An indurative process was noted
      at the site of injection (skin) during the course of immunization. Mixtures of
      the filtrates with their homologous antisera, obtained from animals immunized by
      the intravenous route, and injected into skin, also failed to obliterate the
      erythema and edema. The observations of Shwartzman have been confirmed; the
      Shwartzman phenomenon appears to be group or species specific. Filtrates from
      enterococci failed to produce the phenomenon. Filtrates of other unrelated
      organisms have not been studied. The products of Shwartzman and of Ecker and
      Rimington appear to be the same.

PMID- 19869701
TI  - CHANGES IN HUMORAL IMMUNITY OCCURRING DURING THE EARLY STAGES OF EXPERIMENTAL
      PNEUMOCOCCUS INFECTION.
AB  - A study was made of the changes in humoral immunity occurring during the early
      phases of experimental pneumococcus infection in the dog and cat. The methods
      devised by Robertson and Sia were employed to demonstrate the presence of anti
      pneumococcus properties in the serum of animals naturally resistant to this micro
      organism. It was found that with a generalized and overwhelming infection
      accompanied by early blood invasion, there was a prompt and rapid decrease in the
      concentration of natural humoral immune bodies which frequently disappeared
      entirely by the time of death. This same early diminution of humoral immune
      substances, opsonins, agglutinins, and pneumococcidal-promoting bodies was
      observed in animals that survived a moderately severe generalized infection but
      the concentration of immune bodies rose again with the onset of recovery. The
      decrease in concentration of humoral immune substances during a severe
      generalized infection appeared to be due to the combination of "S" substance with
      the normal immune bodies. When the pneumococcus infection was more localized as
      in the case of true lobar pneumonia a quite different sequence of events was
      observed to occur. Several animals, in which extensive lobar pneumonia was
      produced, showed the presence in quantity of humoral immune bodies in the blood
      throughout the course of an infection terminating fatally. These findings suggest
      that after the inception of pneumococcus infection in the dog and cat the chief
      function of natural anti-pneurnococcus substances in the blood is to limit or
      prevent blood invasion. When pneumococcic infection is localized these
      circulating antibodies appear to have little effect either in preventing the
      spread of the process or determining the outcome of the disease.

PMID- 19869702
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : I. THE ANTIBODY RESPONSE.
AB  - 1. Sixty rabbits were immunized by the repeated injections into the skin of small
      doses of suspensions of heat-killed Type I pneumococci. In 53 of the rabbits no
      type-specific antibodies appeared in the serum, and in the remaining seven the
      titre of these antibodies in the serum was very low. In all cases, however, the
      sera possessed a high titre of species-specific antibodies. 2. Forty-five rabbits
      similarly immunized by injections of heat-killed Type III pneumococci also failed
      to form type-specific antibodies but did form species-specific antibodies. 3.
      Suspensions of heat-killed R pneumococci and solutions of bacterial substances
      when injected into the skin stimulated the production of species-specific
      antibodies, although they failed to stimulate the production of any type-specific
      antibodies. 4. Animals which had been immunized by intracutaneous injections
      still possessed the ability to form type-specific antibodies when they were
      subsequently given intravenous inoculations of type-specific pneumococci.

PMID- 19869703
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : II. RESISTANCE TO INFECTION.
AB  - 1. Injection of suspensions of heat-killed pneumococci into the skin of rabbits
      is followed by an active immunity which is effective against intravenous
      infection by homologous and heterologous types of Pneumococcus. 2. This form of
      active immunity may be induced by the injection of S or R strains of
      Pneumococcus. 3. Intracutaneous immunization with soluble derivatives of
      Pneumococcus does not induce active immunity to infection. 4. The sera of seventy
      nine per cent of the rabbits immunized to Type I Pneumococcus by intracutaneous
      injections afforded no protection to mice against infection with pneumococci. 5.
      None of the sera of rabbits intracutaneously immunized to the type-specific Type
      III (S) pneumococci, to R cells, or to soluble derivatives of Pneumococcus
      protected white mice against infection. 6. The sera of rabbits immunized first
      intracutaneously and subsequently intravenously possess a high titre of
      protective antibodies. 7. It may be concluded that when type-specific pneumococci
      are injected into the skin they lose the property of stimulating an active
      immunity of a specific type and of stimulating the production of type-specific
      antibodies, but they act just as do the degraded or R forms, causing the animals
      to become resistant to infection with pneumococci of all types without the
      development of any type-specific antibodies in the serum.

PMID- 19869704
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : III. REACTIONS AT THE SITE OF INJECTION.
AB  - 1. Following repeated intracutaneous injections of heat-killed pneumococci
      rabbits acquire an increased skin reactivity. 2. The increased skin reactivity
      reaches a maximum after 4 to 6 injections have been made, after which it becomes
      greatly diminished. 3. The relationship of increased skin reactivity to active
      resistance to infection by Pneumococcus, and to the presence of species-specific
      antibodies in the blood, is still obscure. 4. The increased skin reactivity is
      not transferable by serum from a highly reactive to a normal rabbit. 5. After
      regression of the reaction to the first injection of Pneumococcus into the skin,
      there frequently follows a recrudescence, or exacerbation, of the reaction. 6.
      The increased skin reactivity and secondary reactions are incited alike by all
      types and all forms of Pneumococcus.

PMID- 19869705
TI  - THE IMMUNOLOGICAL SIGNIFICANCE OF COLOSTRUM : I. THE RELATION BETWEEN COLOSTRUM,
      SERUM, AND THE MILK OF COWS NORMAL AND IMMUNIZED TOWARDS B. COLI.
AB  - The protective antibody content of normal cow serum is below that of colostrum of
      the same animal. The method used does not permit the titration of the actual
      amount of the antibody in serum. Quantities up to 2 cc. have no protective
      effect. The same limitations apply to the titration of milk owing to the
      introduction of large quantitites of foreign protein into the peritoneal cavity
      of the guinea pig. When cows were immunized and a serum of high titer obtained,
      the antibodies in the milk of such cows rose to within the range of the method of
      testing. The relation of the protective capacity of serum to that of milk was
      approximately 1/120 and 1/40 in the two animals. These figures do not differ much
      from those obtained by early investigators titrating the antitoxic content of
      serum and milk of animals undergoing immunization with diphtheria toxin. In the
      two experiments on calves, 2(1/4) and 18 days old respectively, fed a highly
      protective serum, no increase in agglutinins or protective antibodies could be
      demonstrated. The postponement of colostrum to the 12th and 18th hour,
      respectively did not prevent normal growth.

PMID- 19869706
TI  - THE IMMUNOLOGICAL SIGNIFICANCE OF COLOSTRUM : II. THE INITIAL FEEDING OF SERUM
      FROM NORMAL COWS AND COWS IMMUNIZED TOWARDS B. COLI IN PLACE OF COLOSTRUM.
AB  - Under certain safeguards, such as isolation, calves from a large dairy herd have
      been raised by feeding normal and immune cow serum in place of colostrum. The
      losses were about one out of ten in the later experiments. This outcome may
      probably be improved by the subcutaneous injection of serum during the first day.
      This loss may be no greater than that under ordinary conditions, since sporadic
      deaths among calves are not infrequent. However, no satisfactory statistics are
      available for comparison with results as given above.

PMID- 19869708
TI  - THE IMMUNOLOGICAL SIGNIFICANCE OF COLOSTRUM : III. INTRANUCLEAR BODIES IN RENAL
      DISEASE OF CALVES.
AB  - Renal lesions chiefly the result of obstructive processes were associated with
      intranuclear bodies in the epithelium of straight and convoluted tubules. In one
      animal these bodies were found in large numbers in otherwise still normal organs.
      The affected animals had been fed cow serum in place of colostrum.

PMID- 19869707
TI  - THE RELATIONSHIP OF YELLOW FEVER OF THE WESTERN HEMISPHERE TO THAT OF AFRICA AND
      TO LEPTOSPIRAL JAUNDICE.
AB  - 1. The yellow fever now in South America, the present yellow fever of Africa and
      the historic yellow fever of Panama and other American countries are the same
      disease. This conclusion is based on cross immunity tests in monkeys with strains
      of yellow fever virus from Africa and Brazil and on tests of sera from 25
      persons, who had recovered from yellow fever in various places and at various
      times, for the power to protect monkeys against African or Brazilian virus
      strains. 2. Cases of leptospiral jaundice (Weil's disease) were present among
      those diagnosed as yellow fever in the recent epidemic in Rio de Janeiro. This is
      shown by the isolation of cultures of leptospirae from the blood of two patients
      by H. R. Muller and E. B. Tilden of The Rockefeller Institute, and by the
      demonstration by us of protective power against leptospirae and absence of
      protective power against yellow fever virus in the sera from two persons after
      recovery. The isolation of leptospirae by Noguchi and other investigators from
      the blood of occasional patients in past epidemics of yellow fever in a number of
      American countries indicates that leptospiral jaundice was present then as well
      and was diagnosed clinically as yellow fever. 3. The absence of protective power
      against leptospirae shown by the Brazilian sera which protected against yellow
      fever virus and the absence of protective power against yellow fever virus in the
      sera that protected against leptospirae point to the probability that American
      yellow fever is not the combined effect of leptospirae and yellow fever virus.
      The position of L. icteroides, isolated by Noguchi during yellow fever epidemics,
      now appears to be not that of a secondary invading microorganism in cases of
      virus yellow fever, but that of the incitant of a form of infectious jaundice,
      sometimes fatal, often coincident in its appearance with typical yellow fever and
      apparently indistinguishable from it clinically. This leptospiral disease has not
      hitherto been separated from true yellow fever. Noguchi's discoveries become;
      therefore, of the greatest significance in respect to the epidemiology and
      causation of yellow fever and of infectious jaundice, previously confused one
      with the other. In all outbreaks of supposed yellow fever hereafter the existence
      of the two kinds of jaundice, one due to yellow fever virus and the other to
      leptospirae will have to be taken into account. Only the former probably is
      spread by mosquitoes and requires anti-mosquito measures for its control. 4. The
      only difference observed by us between the American and African strains of yellow
      fever virus was a pronounced difference in virulence for monkeys. The virulence
      of the two African strains studied was very high while that of the one American
      strain was highly variable and usually low.

PMID- 19869709
TI  - STUDIES ON VITAL STAINING : IV. INDIA INK AND BRILLIANT VITAL RED. IMPORTANCE OF
      CONSIDERING LIVER EXCRETION IN THE STUDY OF "BLOCKADE OF THE RETICULO-ENDOTHELIAL
      SYSTEM".
AB  - When brilliant vital red is injected into the blood stream of dogs much of it is
      slowly taken up into numerous phagocytes scattered throughout the tissues
      ("reticulo-endothelial system" of Aschoff). The rate at which the dye leaves the
      blood stream is determined in large part by the action of these phagocytic cells,
      but the excretion of dye into the bile is also in part responsible for the loss
      of dye from the plasma. The injection of a small amount of India ink into the
      blood stream results in lowering the rate at which the dye disappears from
      circulation. The fact that much of the carbon of the ink is promptly taken up by
      the phagocytes would lead one to suspect that they were saturated with foreign
      materials, or "blocked" against the entrance of dye, but it is shown that the ink
      causes a remarkable inhibition of the excretion of dye into the bile, and this
      alone seems to account for the longer retention of dye in the blood stream. There
      is no evidence that any of the retention is due to defective activity on the part
      of the phagocytes. Thus, prolonged retention of foreign materials in the blood
      stream cannot be cited to prove "blockade of the reticulo-endothelial system"
      unless one can rule out such peculiar reactions on the part of excretory organs.
      It is felt that the literature of "blockade" should be studied with such sources
      of error in mind. Preliminary studies indicate that the suppression of dye
      excretion by the liver is not due to the carbon content of the ink. Studies of
      other components of the ink are now in progress.

PMID- 19869710
TI  - STUDIES ON VITAL STAINING : V. DOUBLE STAINING WITH BRILLIANT VITAL RED AND
      NIAGARA SKY BLUE. CORRELATION OF HISTOLOGICAL WITH PHYSIOLOGICAL DATA.
AB  - Vital staining reactions of brilliant vital red and Niagara sky blue are studied
      in dogs and in rabbits. Either dye alone is taken up to form red or blue granules
      within the cytoplasm of macrophages and of certain other cell types. When the two
      dyes are injected simultaneously into the blood stream one finds that these cells
      build up granules which are purple from admixture of the two dyes. When several
      daily injections of one dye are followed by several daily injections of the
      other, one finds blue granules and red granules side by side within the cells,
      but no purple granules are found. This is thought to indicate that the dye is
      deposited in small foci which are active in a rather transitory way, and that the
      color of the granule is determined during its formative stage by the type of dye
      present in the fluids about the cell. The enlargement of phagocytic cells and the
      increase in their number with large dosage, or with repeated offerings of the
      dye, represents a method by which the cells maintain their phagocytic powers at
      the normal level. Evidence is offered to indicate that these and perhaps other
      compensatory changes may take place with great rapidity, so that it has been
      impossible to "block" or even reduce noticeably the ability of these cells to
      take up additional quantities of dye. Certain pitfalls in the experimental study
      of "blockade" are pointed out.

PMID- 19869711
TI  - CONCERNING THE SPECIFICITY AND NATURE OF THE PHENOMENON OF LOCAL SKIN REACTIVITY
      TO VARIOUS BACTERIAL FILTRATES.
AB  - The specifcity and the nature of the phenomenon of local skin reactivity to
      various microorganisms have been studied. It has been shown that the skin
      preparatory and reacting factors of various biologically and serologically
      unrelated microorganisms are able to substitute for each other, provided they
      have the power of eliciting the phenomenon for themselves. Additional evidence
      has been brought concerning the antigenic specificity of the factors eliciting
      the phenomenon. A variety of nonbacterial substances which are able to increase
      the permeability of capillaries, elicit inflammation and "block" the reticulo
      endothelial cells; failed to induce the state of local skin reactivity to B.
      typhosus culture filtrate. Non-bacterial protein substances (crystalline egg
      albumin and normal horse serum) failed to reproduce the phenomenon. It was not
      possible to obtain passive transfer of the local skin reactivity. Various
      conditions influencing the potency of the bacterial culture filtrates have been
      pointed out. The essential nature of the phenomenon has been discussed together
      with its significance in relationship to disease.

PMID- 19869712
TI  - ORAL IMMUNIZATION AGAINST THE PNEUMOCOCCUS : USE OF BILE SALT DISSOLVED
      ORGANISMS, ETC., TIME OF APPEARANCE OF IMMUNITY AND DOSAGE.
AB  - 1. Feeding heat killed pneumococci grown in milk produces a fair degree of
      immunity. 2. Feeding acid killed degraded aruvilent organisms produces little
      protection. 3. Feeding the desiccated, mechanically disrupted organisms creates a
      high degree of protection. 4. Feeding the Berkefeld filtrate of sodium
      glycocholate dissolved cells produce a high degree of immunity. 5. A single
      ingestion of this material equivalent to between 1 and 5 cc. growth is sufficient
      to protect a rat against 1000 to 10,000 fatal doses. Among rats fed the
      equivalent of 0.1 cc. an occasional one survives. 6. This degree of protection is
      present 48 hours after the feeding, and to a smaller extent exists in occasional
      animals at the end of 24 hours. 7. The treated animals are resistant to
      subcutaneous as well as intraperitoneal injections. 8. A single ingestion of
      hydrochloric acid killed pneumococci equivalent to between 1 and 5 cc. growth
      also protects within 48 hours against 1000 to 10,000 fatal doses
      intraperitoneally injected. 9. Reference is made to results obtained in
      preliminary experiments with human beings.

PMID- 19869713
TI  - THE EFFECT ON THE RATE OF UREA EXCRETION OF CARMINE DEPOSITION IN THE CELLS OF
      THE RENAL TUBULES.
AB  - The evidence that urea is present in high concentration in the cells of the
      convoluted tubules of the kidney and is passing through these cells has been
      reviewed. Following the deposition of a large amount of carmine in the cells of
      the convoluted tubules the rate of urea excretion, as measured by the relation of
      the rate of urea excretion to the blood urea concentration, is increased. This is
      interpreted as due to blockage or damage to the cells of the convoluted tubules
      which interferes with their usual function of absorption of urea and other
      substances from the glomerular filtrate and hence increases the amount of urea
      which reaches the bladder urine at a given blood urea concentration.

PMID- 19869714
TI  - STUDIES ON THE COMMON COLD : III. THE UPPER RESPIRATORY FLORA OF INFANTS.
AB  - 1. The upper respiratory tract is sterile at birth. 2. In the first 2 weeks of
      life the infant acquires a basal flora comparable to that of adults except that
      the potential pathogens are absent. 3. During the ensuing months the potential
      pathogens may appear without giving rise to symptoms and by 8 months the infant's
      flora is entirely comparable to the adult's. 4. There is no evidence of a
      specific bacterial incitant for the first colds of infancy. 5. In infants with
      recurrent colds, secondary infection of the nose with pneumococci or B. pfeifferi
      probably plays a part.

PMID- 19869715
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : IV. THE DEVELOPMENT OF SKIN REACTIVITY TO DERIVATIVES OF PNEUMOCOCCUS.
AB  - 1. A skin reaction elicited by the injection of the Pneumococcus "nucleoprotein,"
      or of a solution of the cells from which the acid and heat-coagulable proteins
      have been removed is described in rabbits which have previously received repeated
      intracutaneous injections of heat-killed pneumococci. 2. In terms of bacterial
      specificity, the skin reaction is considered to be not type-specific, but species
      specific. 3. A similar skin reaction to the proteins of Pneumococcus occurs in
      rabbits following the repeated administration by the intravenous or
      intracutaneous route of the heat-killed organisms or their protein derivatives.
      4. The skin reaction may occur independently of resistance to infection. 5. The
      skin reaction appears to be related to the presence of circulating species
      specific antibodies.

PMID- 19869716
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : V. THE DEVELOPMENT OF EYE REACTIVITY TO DERIVATIVES OF PNEUMOCOCCI.
AB  - 1. About two-thirds of the rabbits injected intracutaneously with suspensions of
      heat-killed S or R pneumococci develop an increased eye reactivity. 2. Eye
      reactions in these animals may be elicited by the instillation of
      "nucleoprotein," or of a solution of Pneumococcus from which the acid
      precipitable and heat coagulable proteins have been removed. The eye reactions
      are not elicited, under the conditions described, by living R cells or the
      protein-free, type-specific, polysaccharides. 3. Rabbits do not develop an
      increased eye reactivity following intravenous injections of the intact cell. 4.
      Rabbits do not develop an increased eye reactivity following injections of
      soluble derivatives of Pneumococcus. 5. Experimental infection by Pneumococcus
      may stimulate eye reactivity in rabbits. 6. Eye reactivity occurs in animals
      actively resistant to infection. 7. Eye reactions are observed more frequently in
      rabbits which show the secondary reaction.

PMID- 19869717
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : VI. HYPERSENSITIVENESS TO PNEUMOCOCCI AND THEIR PRODUCTS.
AB  - 1. Rabbits receiving either intracutaneous or intravenous injections of
      crystalline egg albumin acquire a "skin sensitivity" but not an "eye sensitivity"
      to the albumin. 2. Rabbits receiving either intracutaneous or intravenous
      injections of the "nucleoprotein" of Pneumococcus acquire a specific "skin
      sensitivity" to the "nucleoprotein" but not an "eye sensitivity." 3. Rabbits
      receiving intravenous injections of a suspension of heat-killed pneumococci
      acquire a "skin hypersensitiveness" but not an "eye hypersensitiveness" to the
      "nucleoprotein." 4. The skin hypersensitiveness to the respective proteins is
      associated with the presence of antibodies in the blood and is transferable by
      the injection of serum from an actively sensitized to a normal rabbit. 5. Rabbits
      receiving intracutaneous injections of a suspension of heat-killed pneumococci
      also acquire a "skin hypersensitiveness" to the "nucleoprotein" of the cell, but
      they may acquire an eye hypersensitiveness as well. 6. Rabbits injected
      intracutaneously with a suspension of heat-killed pneumococci show a primary and
      a secondary skin reaction following the first injection. The intensity of the
      reactions increases with subsequent injections up to the fourth to the sixth
      injection. With later injections these reactions change in character and decrease
      in intensity. These reactions bear no apparent relation to the presence of
      antibodies in the blood. 7. Rabbits injected intracutaneously with a suspension
      of heat-killed pneumococci develop "eye hypersensitiveness" which, under the
      experimental conditions, is not transferable from "eye reactive" to normal
      rabbits. 8. It appears, therefore, that following the injection of heat-killed
      pneumococci into the skin a special kind of "eye" and "skin hypersensitiveness"
      develops which is not related to the presence of circulating antibodies and which
      cannot be transferred from the sensitive to normal rabbits.

PMID- 19869718
TI  - STUDIES ON LEUKEMIA IN MICE : I. THE EXPERIMENTAL TRANSMISSION OF LEUKEMIA.
AB  - Lymphatic leukemia has occurred with great frequency in a particular strain of
      mice which have been inbred by brother-sister matings since 1921. In addition to
      typical cases of leukemia are others which, because of the absence of leukemic
      changes in the blood, correspond to "pseudoleukemia" and others which, by the
      presence of unusually great enlargement of certain lymph node groups resemble the
      "leukosarcomatoses" as observed in man. Examinations of the blood of leukemic
      mice have shown that leukemic blood pictures are not necessarily early in their
      appearance, nor are they constant. The blood picture may not, therefore, be used
      as a criterion for the separation of the two diseases (leukemia and
      pseudoleukemia) but merely indicates different phases of the same condition.
      Likewise, cases with lesions intermediate between the local growths of
      "leukosarcomatosis" and the more general lymphatic enlargements of leukemia
      suggest that these conditions differ only in the distribution of lesions but not
      in their nature. Lymphatic leukemia occurring spontaneously in this strain may be
      transmitted to other mice of the same strain, and carried, apparently, for an
      unlimited number of transfers in animals at an earlier age than that at which
      leukemia occurs spontaneously. In each of 10 such experiments transmissions were
      obtained. The lesions produced by inoculation correspond to those of spontaneous
      cases, in that they consist of growths of abnormal lymphoid cells which
      infiltrate tissues and organs and often appear in the circulating blood. Only
      minor differences have occurred, some of which are characteristic of certain
      experimental lines. After repeated transfers, the disease tends to run a more
      acute course. Among the cases in which transmissions occurred, are some without
      leukemic changes in the blood, and many with local growths at the site of
      inoculation or in certain node groups. The differences in the blood pictures and
      distribution of lesions (which latter may be influenced to some extent by the
      method of inoculation) correspond to similar differences which are sometimes
      observed in the spontaneous cases.

PMID- 19869719
TI  - OBSERVATIONS ON THE PHAGOCYTOSIS OF THE PNEUMOCOCCUS BY HUMAN WHOLE BLOOD : I.
      THE NORMAL PHAGOCYTIC TITRE, AND THE ANTI-PHAGOCYTIC EFFECT OF THE SPECIFIC
      SOLUBLE SUBSTANCE.
AB  - 1. The phagocytic titre of whole human blood against the three types of
      pneumococcus was determined in a number of individuals. The titre varied over a
      considerable range in different subjects. 2. Contrary to expectation, the titre
      in early cases of untreated pneumonia was quite high against the infecting
      organism, pointing to a local rather than a general lowering of resistance in
      infection with this organism. 3. Sia's work was confirmed, that the specific
      carbohydrate has a specific anti-phagocytic action on the blood. This action is
      more marked in the case of Type III than in Type I.

PMID- 19869720
TI  - OBSERVATIONS ON THE PHAGOCYTOSIS OF THE PNEUMOCOCCUS BY HUMAN WHOLE BLOOD : II.
      THE NEUTRALIZATION OF THE ANTI-PHAGOCYTIC ACTION OF THE SPECIFIC SOLUBLE
      SUBSTANCE BY ANTISERUM.
AB  - 1. In vitro phagocytic experiments with human blood, antipneumococcus serum,
      pneumococcus specific soluble substance, and living virulent pneumococci show
      that there is a definite phagocytic inhibition zone when strong antiserum is
      used. 2. If the antiserum is further diluted, there is a zone where phagocytosis
      is effective. If the serum is diluted still more, phagocytosis gradually falls
      off, as the very dilute antiserum fails to neutralize the specific carbohydrate,
      which has a specific antiphagocytic action. 3. The inhibition zone is apparently
      caused by the specific precipitate (formed by the antiserum and the specific
      carbohydrate) interfering, perhaps mechanically, with the ingestion of the
      pneumococci by the leucocytes. 4. The inhibition zone is better marked with Type
      III than with Type I pneumococcus. 5. As the concentration of antiserum in the
      zone of effective phagocytosis in vitro does not correspond with the
      concentration of antiserum generally used in vivo in the serum therapy of
      pneumonia, this question is discussed.

PMID- 19869721
TI  - THE TRANSMISSION OF YELLOW FEVER : EXPERIMENTS WITH THE "WOOLLY MONKEY"
      (LAGOTHRIX LAGO-TRICHA HUMBOLDT), THE "SPIDER MONKEY" (ATELEUS ATER F. CUVIER),
      AND THE "SQUIRREL MONKEY" (SAIMIRI SCIREUS LINNAEUS).
AB  - 1. Saimiri sciureus has been infected with yellow fever virus, both by the
      inoculation of infectious blood and by the bites of infective mosquitoes. Some of
      the monkeys have died, showing lesions, including hepatic necrosis, suggesting
      yellow fever as seen in human beings and in rhesus monkeys. Virus has been
      transferred back to M. rhesus from infected Saimiri both by blood inoculation and
      by mosquito bites. The virus undoubtedly has been maintained through four direct
      passages in Saimiri. Reinoculations of infectious material into recovered monkeys
      have not given rise to invasion of the blood stream by virus. Sera from recovered
      animals have protected M. rhesus against the inoculation of virus. 2. It has been
      possible to pass the virus to and from Ateleus ater by the injection of blood or
      liver and by the bites of mosquitoes. The livers from two infected animals have
      shown no necrosis. The serum from one recovered monkey proved to be protective
      for M. rhesus. 3. Only three out of twelve Lagothrix lagotricha have reacted to
      yellow fever virus by a rise in temperature. Probably none have died as a result
      of the infection. In only one instance has the virus been transferred back to M.
      rhesus. The sera of recovered animals have had a protective action against yellow
      fever virus.

PMID- 19869722
TI  - THE EFFECT OF THE ROUTE OF IMMUNIZATION ON THE IMMUNITY RESPONSE TO PNEUMOCOCCUS
      TYPE I.
AB  - 1. The sera of 80 per cent of the rabbits intravenously inoculated with fixed
      amounts of heat-killed pneumococci contained agglutinins and all showed
      protective antibodies. 2. The sera of 60 per cent of the intraperitoneally
      inoculated rabbits contained agglutinins and all showed protective antibodies. 3.
      The sera of 33 per cent of the intramuscularly inoculated rabbits contained
      agglutinins and 86 per cent also showed protective antibodies. 4. None of the
      sera of the subcutaneously inoculated rabbits contained agglutinins although
      protective antibodies were present in 71 per cent. 5. Although there is a close
      relationship between the presence of agglutinins and protective antibodies in a
      given immune serum, these do not run parallel.

PMID- 19869723
TI  - EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : THE EFFECT OF CROWDING UPON
      TUBERCULOSIS IN GUINEA PIGS, ACQUIRED BY CONTACT AND BY INOCULATION.
AB  - 1. If normal guinea pigs are confined with an equal number of tuberculous cage
      mates the incidence of "contact" tuberculosis is increased by crowding. This is
      probably due largely to an increase in the amount of tubercle bacilli available
      in the more crowded cages, although no constant relationship could be established
      between the intensity of the exposure and the incidence of tuberculosis acquired
      by contagion. Other factors must be determined. 2. If guinea pigs are inoculated
      intraperitoneally with a given quantity of human tubercle bacilli and distributed
      in different degrees of crowding, the duration of survival is shortened in the
      more crowded animals, and the incidence of chronic types of tuberculosis is
      greater among the less crowded animals.

PMID- 19869724
TI  - EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : AIR-BORNE CONTAGION OF TUBERCULOSIS
      IN AN ANIMAL ROOM.
AB  - 1. Guinea pigs living in the same room but not in the same cage with tuberculous
      animals acquire tuberculosis, characterized by a chronic course, a marked
      involvement of the lungs, often with cavity formation and a massive tuberculosis
      of the tracheobronchial nodes; the mesenteric and cervical nodes are slightly or
      not at all affected. 2. The route of infection in these guinea pigs is almost
      always the respiratory tract. 3. Of 103 guinea pigs exposed for a period of up to
      32 months 15 or 14.5 per cent developed tuberculosis. The shortest period of
      exposure leading to fatal tuberculosis was 8 months. 4. The incidence of this
      tuberculosis acquired by air-borne contagion increases with the duration and
      intensity of the exposure up to a certain point. 5. A large percentage of the
      guinea pigs weathered a continuous exposure to the tubercle bacillus for 32
      months without becoming tuberculous. This may be due to an innate natural
      resistance against tuberculosis, or to an acquired immunity resulting from the
      continuous exposure to the contagion.

PMID- 19869725
TI  - EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : THE EFFECT OF ELIMINATING EXPOSURE TO
      ENTERIC INFECTION ON THE INCIDENCE AND COURSE OF TUBERCULOSIS ACQUIRED BY NORMAL
      GUINEA PIGS CONFINED WITH TUBERCULOUS CAGE MATES.
AB  - In these studies normal guinea pigs were exposed to tuberculous cage mates in two
      different degrees of crowding, some in ordinary cages, where the food became
      contaminated with the excreta, laden with tubercle bacilli, of the inoculated
      animals, and some in special cages with wire-mesh floors, where these excreta
      were largely excluded as a source of contagion. The results are summarized in
      Table V. In all these experiments crowding has always increased the incidence of
      the disease both in the ordinary and the special cages. However, due to the
      accident of eating of tuberculous animals in the more crowded cages these results
      are not conclusive, but they are in accord with the results of the previous study
      (2). It was found that the incidence of tuberculosis was lower among the guinea
      pigs exposed to contagion in the special cages, in which little of the
      contaminated excreta remained in direct contact with the normal animals. In fact
      in the less crowded special cages the incidence of tuberculosis was only a little
      higher than among the same total number of guinea pigs exposed at the same time
      in the same room but not confined with tuberculous cage mates. In the special
      cages, especially in the less crowded, where nearly all the contaminated excreta
      were removed, the disease acquired was largely respiratory in origin and was
      characterized by an extensive tuberculosis of the tracheobronchial lymph nodes
      with little or no affection of the mesenteric nodes. The pulmonary disease in the
      guinea pigs that acquired tuberculosis in these cages was more often extensive
      than that acquired in the ordinary cages. However no definite evidence of primary
      lesions in the lung in the former was found, due to the dissemination of the
      disease at the time of death. The tuberculosis acquired by the contacts in the
      ordinary cages, on the other hand, was usually enteric in origin, although both
      routes were involved, especially in the less crowded cages. Moreover, a striking
      fact appears if we compare the course of tuberculosis in these two types of cages
      in both degrees of crowding: the contacts that developed tuberculosis in the
      ordinary cages survived an average of 106 and 114 days longer than the
      corresponding animals in the special cages. It is well known that the respiratory
      route is a far more dangerous avenue of infection in tuberculosis than the
      alimentary canal. This fact has again been clearly brought out in the recent
      studies of Bruno Lange and his associates (3), who have shown that although
      guinea pigs may occasionally be infected by way of the mouth with quantities as
      low as 0.000,001 mg. of virulent tubercle bacilli they often escape infection
      even when fed 0.1 mg. or more. On the other hand if guinea pigs are made to
      inhale even the smallest quantities of tubercle bacilli they regularly contract
      tuberculosis. Furthermore they have also shown that the alimentary infection
      produces a disease far more chronic in character than that acquired by the
      respiratory route. It would therefore seem that the more acute type of disease is
      acquired in the special cages because in these cages the respiratory route plays
      by far the more important ro1e whereas in the ordinary cages the disease is
      largely of enteric origin. However, it appears that in the ordinary cages where
      the guinea pigs were constantly stirring up their sawdust or peat-moss bedding,
      laden with tubercle bacilli, there was an even greater opportunity for
      respiratory infection than in the special cages where there was no bedding at all
      and where most of the excreta were removed from immediate contact with the normal
      animals. That the respiratory mode of infection plays a ro1e even in the ordinary
      cages was shown in a previous communication (2) as well as in this paper. In both
      studies it was found that only in the more crowded ordinary cages is the disease
      almost entirely of enteric origin but in the less crowded ordinary cages
      infection takes place by the respiratory tract as well, though to a smaller
      degree than by the alimentary. It would therefore appear that in the ordinary
      cages both routes are open for infection but the relatively larger doses of
      tubercle bacilli ingested determine a disease of enteric origin and hence of a
      chronic nature, suppressing at the same time the engrafting of the disease by way
      of the lungs, and that in the special cages where the alimentary sources of
      infection have been reduced to a minimum, the disease is engrafted by way of the
      lungs and is therefore of more acute type. Although in the special cages the
      intensity of exposure even to tubercle bacilli entering by the respiratory tract
      is less than in the ordinary cages, nevertheless the disease so produced is more
      acute, presumably because the inhibitory or retarding effect of enteric infection
      upon the development of respiratory disease is absent. This explains the
      paradoxical effect observed of a greater incidence and a more chronic type of
      disease in the ordinary cages and a lower incidence and a more acute type of
      disease in the special cages, for the intensity of exposure by both routes is
      greater in the ordinary cages, and of the two, much greater by the enteric route.

PMID- 19869726
TI  - EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : THE ROUTE OF INFECTION IN NATURALLY
      ACQUIRED TUBERCULOSIS OF THE GUINEA PIG.
AB  - Under conditions closely simulating the natural modes of tuberculous infection in
      man normal guinea pigs have acquired tuberculosis by being exposed under two
      degrees of crowding to tuberculous cage mates in ordinary cages, where the food
      became soiled with excreta, bearing tubercle bacilli, and in special cages, with
      wire-mesh floors, where this source of infection was almost entirely eliminated.
      Guinea pigs were also exposed in the same room but not in the same cage with
      tuberculous animals. It was found that the relative tuberculous involvement of
      the mesenteric and tracheobronchial nodes showed a gradation of change from an
      almost completely alimentary infection to a completely respiratory infection. The
      disease involved the mesenteric nodes predominantly in the crowded ordinary
      cages, with much less or no affection of the tracheobronchial nodes. It was
      similarly, but less markedly, enteric in origin in the less crowded ordinary
      cages, the mesenteric nodes again being larger than the tracheobronchial nodes,
      but the difference in size was not so great. In the more crowded special cages
      the relative affection of these two groups of nodes alternated, so that in some
      the mesenteric, in some the tracheobronchial nodes were more extensively
      tuberculous. A disease characterized by less or no affection of the mesenteric
      nodes and by extensive lesions of the tracheobronchial nodes was seen in the less
      crowded special cages. Finally there was a massive tuberculosis of the
      tracheobronchial nodes with usually no affection of the mesenteric nodes in the
      frankly air-borne tuberculosis acquired by guinea pigs exposed in the same room
      but not to tuberculous cage mates. This gradation in the ro1e played by the
      enteric and respiratory routes of infection, as first the one and then the other
      becomes the more frequent channel of entrance for tuberculosis, would indicate
      that the penetration of tubercle bacilli by the one portal of entry inhibits the
      engrafting of tuberculosis in the tissues by way of the other portal of entry. It
      is apparent that in the special cages the opportunities for inhaling tubercle
      bacilli are at most equal to if not much less than in the ordinary cages; for in
      the latter dust from the bedding, laden with tubercle bacilli, is stirred up
      almost constantly by the animals, whereas in the special cages there is no
      bedding at all, and therefore, presumably, no more tubercle bacilli in the air
      than may occur in any part of the room. Nevertheless the route of infection was
      predominantly the respiratory tract in the special cages, especially in the less
      crowded, apparently because the enteric route had been largely eliminated. The
      greater predominance of the respiratory route amongst guinea pigs that acquired
      tuberculosis in the less crowded ordinary cages as compared to the lesser
      significance of this route in the more crowded ordinary cages would point in the
      same direction. These observations are in harmony with our knowledge that
      tuberculosis once implanted in an organism confers a certain degree of immunity
      to the disease. It is noteworthy that in a study of human autopsy material Opie
      (3) has found that when healed lesions are present in the mesentery focal
      tuberculosis in the lungs is seldom found, and that when first infection occurs
      by way of the lungs it tends to prevent the engrafting of the disease by way of
      the intestinal tract.

PMID- 19869727
TI  - EXPERIMENTS WITH THE VIRUS OF POLIOMYELITIS.
AB  - 1. Efforts to adapt the virus of poliomyelitis to the rabbit organism and to
      produce poliomyelitis in rabbits by testicular injection and by brain injection
      after testicular passage produced no evidence that the virus could be adapted in
      this manner. Suggestive symptoms produced in very young rabbits were duplicated
      in non-specifically treated and in uninoculated controls. The admixture of a
      vaccine virus, adapted to the rabbit organism, with the poliomyelitis virus in
      similar injections and passages did not aid the adaptation. The virus of
      poliomyelitis did not survive 24 hours in the rabbit testicle-whether alone or
      mixed with vaccine virus. Repeated intraperitoneal and intradermal injection of
      poliomyelitis virus and of poliomyelitis and vaccinia virus mixtures produced no
      disease in rabbits. Massive doses of concentrated virus by stomach tube in
      conjunction with meningeal irritation produced no symptoms in rabbits. 2. No
      neutralizing substances against poliomyelitis virus could be produced in rabbits
      by the repeated intraperitoneal and intradermal injection of poliomyelitis virus
      or of poliomyelitis-vaccinia virus mixtures. 3. Although attempts to infect
      monkeys by intrastomachic injections, after bile irritation of the mucosa, were
      entirely negative, evidence was obtained that repeated intrastomachic injection
      after bile irritation may produce an appreciable degree of immunity. 4. No
      evidence could be obtained that the cellular elements of the blood contain the
      virus in any greater proportion than the whole blood. 5. One attempt to immunize
      by neutral virus-serum mixtures was entirely negative.

PMID- 19869728
TI  - METHODS FOR THE PURE CULTURE OF CERTAIN PROTOZOA.
AB  - Some media are described which inhibit bacterial growth, but are favorable to
      protozoan development. A purification technique, which takes advantage of
      geotropic responses, was devised and used successfully with 7 species of
      protozoa, including flagellates and ciliates. The method was also used with a
      Spirillum. For one flagellate which could not be purified in this manner, a
      procedure involving chemical sterilization was employed. Paramecium caudatum was
      purified, but failed to develop subsequently in the absence of living
      microorganisms. Four of the protozoa which were purified ingest other
      microorganisms normally. The work shows that purified protozoa grow well under
      proper conditions, and then they can be studied culturally and biologically, like
      bacteria.

PMID- 19869730
TI  - BIOLOGICAL STUDIES OF THE TUBERCLE BACILLUS : I. INSTABILITY OF THE ORGANISM
      MICROBIC DISSOCIATION.
AB  - The recent advances in the study of the other bacteria with application to the
      dissociation phenomenon, have been applied in the study of acid-fast organisms.
      For some time, we have realized that the term "dissociation" as employed at
      present, is not adequate to explain the instability and subsequent variation
      which occur in cultures. But for uniformity of bacteriological nomenclature, we
      have adopted the term until a better one is coined. In describing the "R" and "S"
      colonies, we have had to depart somewhat from the general usage of these terms,
      that is the "R" meaning rough, and "S" smooth. The colonies of acid-fast
      organisms are relatively varied and complex. It seems better to employ the letter
      "R" to indicate greater resistance to environment and relative avirulence; and
      "S" to indicate colonies which are more sensitive to environment while possessing
      for certain species relatively great virulence. The terms "rough" and "smooth"
      apply directly only to avian tubercle bacillus, when cultivated on plain gentian
      violet-egg medium. The avirulent colony isolated from this culture is flat and
      somewhat rough in appearance. The virulent is perfectly smooth, round and
      resembling a moth-ball. The physical properties are different. They have been
      fully described elsewhere. When the bovine "R" and "S" are cultivated on plain
      gentian-violet-egg medium, differentiation is very difficult. At times they are
      almost indistinguishable, but the addition of 0.25 per cent sodium taurocholate
      to the medium, alters completely the topography of the colony. The "S" appears in
      perfectly round smooth moth-balls, and the "R" in larger, spreading and somewhat
      rough colonies. Lacking suitable media, the human tubercle bacillus H(37) has
      been more difficult to dissociate. After 2 years' study, using various media, we
      have been able to dissociate two types of colonies; but as the animal experiments
      are not yet completed, very little more than that can be said at present. We have
      dissociated two extreme types of colonies from four BCG cultures obtained from
      various sources. Each of these four cultures has revealed the same types of
      colonies. For details the reader is referred to a recent paper (10). In this
      publication we have included photographs taken from time to time in order to keep
      a record of our observations. When studying the photographs, the reader will
      notice considerable variation in some of the colonies. Unquestionably, there are
      more than two types of colonies developing during the life cycle of the organism,
      but at present we have considered and confined ourselves to only the two extreme
      types, one which can produce progressive disease, leading to the death of the
      animal, and the other which is but slightly virulent, and sometimes not at all so
      for susceptible animals. Full details of the technique employed by us have been
      described in the test. Anyone attempting to duplicate the work must strictly
      adhere to the technique described. Departures from it may lead to failure. The
      underlying factors favoring dissociation are not yet clearly understood. We
      believe that every single bacillus contains the two components, "R" and "S." If
      the environment is favorable for the development of the "R" component, the
      offspring will be "R's," although the original organism may be "S." Conversely,
      if the environment is favorable for the "S" and not for the "R" component the "S"
      will develop. For example, if an avirulent "R" colony obtained from the avian
      bacilli is cultivated on egg medium, which is favorable for the organism, the
      offspring after a suitable length of time will develop "S" colonies.

PMID- 19869729
TI  - THE GRADIENT OF VASCULAR PERMEABILITY.
AB  - The permeability of the capillaries in the skeletal muscles of mammals increases
      progressively along their course and is greatest where they pass into the least
      venules. The gradient of permeability is so largely independent of functional
      states as to give grounds for the view that it is determined by inherent local
      differences. Through the gradient opportunity is equalized along the capillary.
      In the liver lobule this object is accomplished by an artifice of arrangement
      whereby the blood flow past the cells is increased with their distance from the
      source of supply. In the urinary bladder the interlacing of capillaries, their
      progressive widening, and a consequent gradual slowing of the blood flow act to
      achieve the same end. Here a gradient of permeability has not been demonstrable.
      Where cells of different sorts are served by a slender capillary, their differing
      requirements may render unnecessary any provision to equalize their
      opportunities; but where shortcomings in local maintenance will reduce the
      efficiency of an entire fabric, as the muscle fibre, and where cells of like
      character live competitively along the same channel, as in the liver, some
      arrangement must exist to ensure an even distribution of the services rendered by
      the blood. In situations of the kind last mentioned the immediate environment of
      the individual cell, the "milieu interne" of Bernard, is not only kept as
      constant as possible but it must be the same, by and large, for all of the cells.
      The task of serving voluntary muscle is not strictly limited to the capillaries.
      The intrafascicular arterioles and venules act so effectively to sustain the
      tissue about them that where they run no capillaries are supplied.

PMID- 19869731
TI  - STUDIES ON MEXICAN TYPHUS FEVER. I.
AB  - The preceding studies on typhus fever, chiefly done with a Mexican strain
      obtained from Dr. Mooser, concern themselves largely with reinvestigations of
      some of the fundamental problems of this disease. Filtration experiments carried
      out with methods almost regularly successful with true filterable viruses, in
      regard to material, suspension fluid, reaction, nature of filters and pressure
      employed for filtration, indicate that the virus is not filterable in the
      ordinary sense in which this expression is employed. It is probably smaller than
      bacteria and the results of filtration experiments suggest that its magnitude is
      consistent with the tunica bodies observed by Mooser. Negative filtrates did not
      immunize, a result consistent with the previous work of Olitsky. The virus is
      present in blood plasma, hardly if at all in leucocytes, and becomes closely
      associated with the red blood cells, though we do not believe that it is
      contained in them. It becomes firmly associated with normal red blood cells when
      these are exposed to infectious plasma, a result similar to that obtained in
      Rocky Mountain spotted fever by Spencer and Parker. In tissue culture, tunica
      material with Mooser bodies remains alive and virulent for about 10 days, but so
      far we have not been able to determine that it can keep alive without the
      presence of living cells. These results do not carry this subject any further
      than it has been carried for European typhus in tissue cultures with the same
      method by Wolbach, Schlesinger and Pinkerton (12). Within glass capsules in the
      peritoneum of guinea pigs, the virus may remain alive for about the same length
      of time as in the tissue cultures. Rough comparative virulence estimations
      between blood plasma in which it would be hardly possible to find a limited
      number of Mooser bodies, even though they were present, showed the blood plasma
      to be less infectious than the tunica material, in which considerable numbers of
      Mooser bodies were visible. The testicular swelling characteristic of Mexican
      typhus and showing the above mentioned bodies-probably Rickettsia-may be absent
      in individual guinea pigs under ordinary conditions and in guinea pigs inoculated
      by other than the intraperitoneal route. On re-inoculation into the peritoneum
      after non-orchitic passages, the swelling reappears. Whenever it did not so
      reappear, we found that the strain had either degenerated in virulence or it had
      been contaminated by intercurrent infection. Though we can not prove it at the
      present time, we believe that the tunica lesion is an integral part of this
      disease in guinea pigs, and not an accidental accompaniment. Convalescent blood
      from Mexican typhus guinea pigs mixed in the test tube with virus affords
      protection if the blood is taken between the first to the tenth day after
      defervescence. After the third week, the blood no longer contains protective
      bodies although the guinea pigs may still be immune. In one case a serum was
      obtained which was both protective in such a test but at the same time seemed
      still to contain virus, a result which we cannot explain. No complement-fixing
      antibodies were found when virus serum was used as antigen and convalescent serum
      as antibody. The low concentration of the virus in the serum may account for
      this. In a limited number of observations guinea pigs which were negatively
      inoculated with virus-serum mixtures proved on re-inoculation to be immune. In
      one of these cases the protective serum mixture with the virus was taken 1 day,
      in the other 5 days after temperature had returned to normal and the re
      inoculations were done 36 and 40 days after the primary injection. This recalls
      similar experiences of Nicolle and encourages further immunological study in this
      direction. In a number of experiments active immunization with formalinized
      tunica material containing large numbers of the Mooser bodies seems to have
      modified the course of subsequent inoculations in the direction of protection. A
      single accidental human infection seemed particularly associated with tunica
      material, although this cannot be positively asserted. All that part of our work
      which has bearing on the infectious agent is consistent with the assumption that
      the small, Giemsa-staining bodies observed by Mooser in the tunica of Mexican
      typhus guinea pigs represent the virus of the disease.

PMID- 19869732
TI  - CENTRIFUGE EXPERIMENTS WITH THE VIRUS OF VACCINIA.
AB  - Centrifuge experiments have been carried out with cell-free, active filtrates of
      vaccinia virus. The experiments have shown that the virus can be concentrated by
      this method, even in filtrates which have been subjected to prolonged preliminary
      centrifugation to throw down any inert particles which may have been present in
      the original filtrate. This fact, together with the knowledge that the virus can
      be almost completely held back by the Berkefeld N filter, as reported previously
      (5) indicates that the virus may be of considerable size.

PMID- 19869733
TI  - TOTAL WATER AND CHLORIDE CONTENT OF DEHYDRATED RATS.
AB  - The circumstances present in upper intestinal obstruction which may be expected
      to reduce the water content of the body are fasting with water deprivation and a
      continued loss of secretions into the stomach. According to the data obtained
      from the above described experiments with rats, loss of body water during the
      first third of the survival period following pyloric obstruction is more than
      half accounted for by fasting with water deprivation. This body water is
      accompanied by a parallel loss of solids and may be regarded as a waste product
      of the consumption of body fat, glycogen, and protoplasm. Its loss does not
      disturb the per cent water content of the body tissues. The water lost into the
      stomach is responsible for an actual excess of water reduction over consumption
      of solids. Except in the case of the skin and blood, this excess loss of water is
      extremely small and produces a reduction of the per cent water content of tissues
      which is so slight as to permit the surmise that the water loss here derives
      entirely from the interstitial fluid of the tissues and that no dehydration of
      tissue cells occurs. The data are, however, not directly informative on this
      point. The total loss of body water during 12 hours following pyloric obstruction
      was found to be 12.6 per cent of the water content of a control animal. More than
      one-quarter (28.3 per cent) of the total body content of chloride ion was found
      to be lost and was entirely accounted for by the amount of chloride found in the
      gastric contents. Nearly half of the chloride loss derives from the skin. Data
      are presented which demonstrate that lower intestinal obstruction causes slight,
      if any, depletion of the water content of the body.

PMID- 19869734
TI  - STUDIES ON INFLAMMATION : III. FIXATION OF A METAL IN INFLAMED AREAS.
AB  - Colloidal iron or ferric chloride injected into the inflamed peritoneal cavity is
      fixed in the cavity and fails to reach the retrosternal lymphatic nodes, whereas,
      in the absence of inflammation, iron accumulates in these nodes and becomes
      demonstrable by the Prussian blue reaction. Quantitative studies show that after
      intraperitoneal injection of ferric chloride the retrosternal lymphatic nodes of
      animals with normal peritoneal cavity contain approximately 56 per cent more iron
      than do the nodes of animals with inflamed peritoneal cavity. Ferric chloride
      injected into the circulating blood enters an inflamed area in the skin and the
      inflamed tissue gives the Prussian blue reaction. Quantitative determinations
      show that the amount of iron in inflamed areas is much greater than that found in
      inflamed areas of animals that have received no iron.

PMID- 19869735
TI  - ACCUMULATION OF ANTIBODIES IN THE CENTRAL NERVOUS SYSTEM.
AB  - 1. Antibodies can be extracted from the brain and spinal cord of rabbits actively
      or passively immunized with typhoid bacilli. 2. The titers of the antibodies in
      the extracts of brain and cord depend upon the titer of the blood serum. In
      actively immunized rabbits the following numerical relationships exist between
      the titers of the serum and of these organ extracts: The ratio of the titer of
      the serum is to the titers of extract of brain and of the spinal cord about as
      100 is to 0.8; the titer of the serum is to the titer of the cerebrospinal fluid
      as 100 is to 0.3. In passively immunized rabbits the titer of the serum is to the
      titer of brain and spinal-cord extract as 100 is to 0.7. 3. The antibodies
      recovered from the brain are not due to the presence of blood in it for perfusion
      of the brain does not reduce its antibody content appreciably. 4. Antibodies
      penetrate into the spinal fluid from the blood even in the absence of
      inflammation of the meninges. When the penetration is completed the following
      numerical relationship exists between the titer of the serum and that of the
      cerebrospinal fluid: 100 to 0.25. 5. The penetration into the cerebrospinal fluid
      of antibodies injected intravenously proceeds at a slow rate, being completed
      only several hours after the immune serum has been injected. The penetration of
      antibodies into the tissue of the brain occurs at a very rapid rate. It is
      completed within 15 minutes. 6. It is very unlikely that when the immune serum is
      injected intravenously the antibodies reach the brain tissue by way of the
      cerebrospinal fluid, for (1) the antibody titer of the cerebrospinal fluid is
      lower than that of the brain extract, and (2) antibodies penetrate faster into
      the tissue of the brain than into the cerebrospinal fluid.

PMID- 19869736
TI  - CULTIVATION AND CLASSIFICATION OF "BACTEROIDES," "SYMBIONTS," OR "RICKETTSIAE" OF
      BLATTELLA GERMANICA.
AB  - In Blattella germanica, the German roach or "croton bug," bacteriocytes are found
      in all individuals of both sexes. These bacteriocytes are scattered throughout
      the fat tissue and their cytoplasm is filled with microorganisms. Evidence is
      presented to show that the intracellular parasites are diphtheroidal bacilli.
      These diphtheroids are transmitted from one generation to another through the
      ova. By using a technic previously described, the intracellular parasites were
      isolated and cultivated from the adult bacteriocytes and from embryos. Two
      diphtheroidal strains were cultivated with approximately equal frequency. These
      two strains resemble one another closely enough to be considered a single species
      but show certain minor differences. The sizes, general morphology, and tinctorial
      reactions of the two cultures correspond to the intracellular parasites of
      Blattella germanica. They may be distinguished from the three types of
      Corynebacterium periplanetae variety americana, previously described. For the
      species here discussed the name Corynebacterium blattellae nov. sp. is proposed.

PMID- 19869737
TI  - A CONTRIBUTION TO THE EPIDEMIOLOGY OF SPECIFIC INFECTIOUS CYSTITIS AND
      PYELONEPHRITIS OF COWS.
AB  - Bacteriological examination of the genito-urinary tract of calves originating in
      a herd in which infectious cystitis and pyelonephritis exists among the cows,
      revealed a variety of cultural types of diphtheroids. Of these types, one
      obtained from a considerable number of the calves resembled in morphology and
      cultural characters the organism cultivated from the actual cases of the disease.
      This group had agglutination affinities like those of the organism mentioned and
      was capable of absorbing agglutinin from antiserum specific for it. When three
      cows were inoculated intra-urethrally with cultures isolated from the sheaths of
      calves, two developed transient infections and the other a severe prolonged
      cystitis and pyelonephritis.

PMID- 19869738
TI  - THE EFFECT OF CATHODE RAYS UPON CERTAIN BACTERIA.
AB  - 1. For the two motile bacilli, B. coli and B. aertryke, the absorption of a
      single 155 K.V. electron is sufficient to cause death. Furthermore, all, or
      nearly all, the electrons absorbed are lethal. The same is undoubtedly true of
      Staphylococcus aureus. In addition to providing a quantitative picture of the
      interaction of bacteria and cathode rays, these results suggest that radiation of
      the energy content used in our experiments is not suitable for altering the
      inheritable characteristics of bacteria. 2. The differences in sensitivity to
      cathode rays shown by the bacteria studied can be explained by the purely
      physical factor of size. 3. Counts giving significant conclusions concerning
      killing rates can be obtained only if there is no clumping of the cells when
      spread and only if the cells are not allowed to multiply before irradiation. Both
      these precautions seem rarely to have been met in the experiments that have in
      the past been made with X-rays and other forms of radiation.

PMID- 19869739
TI  - RISE IN TEMPERATURE PRECEDING THE APPEARANCE OF SYMPTOMS IN EXPERIMENTAL
      POLIOMYELITIS.
AB  - The data presented in this paper offer a means of earlier recognition of
      experimental poliomyelitis in the monkey. The early appearance of the temperature
      rise (1 to 3 days before the onset of the usual recognizable symptoms) associated
      with spinal fluid changes suggests that there is a stage in the experimental
      disease corresponding to preparalytic human poliomyelitis.

PMID- 19869740
TI  - ABNORMALITIES PRODUCED IN THE CENTRAL NERVOUS SYSTEM BY ELECTRICAL INJURIES.
AB  - The alternating and continuous circuits produced different types of lesions in
      the central nervous system. Hemorrhages were common after alternating current
      shocks and few hemorrhages were observed in the continuous circuit group. With
      both types of circuits at 1000 and 500 volts potential, severe abnormalities in
      the nerve cells were observed. These were more marked in the continuous circuit
      group. A uniformly staining, shrunken, pyknotic nucleus was taken as a criterion
      of nerve cell death. The Purkinje cells of the cerebellum were most susceptible
      to the current. Injured cells were studied in the dorsal nucleus of the vagus, in
      the somatic motor group, among the primary sensory neurones and in the olives.
      Changes in the histological structure of the cells in reference to recovery have
      been discussed. Injury to the cerebral and cerebellar cortices occurred on the
      dorsal surface close to the head electrode. Small cavities were produced,
      particularly in the cerebral cortex, as the result of the circuit contact. With
      the continuous and alternating circuits at 110 and 220 volts potential less
      severe changes were observed in the nerve cells although hemorrhages were common
      in the alternating circuit group. It must be assumed in these cases that death
      was due to respiratory block rather than actual death of the cells.

PMID- 19869741
TI  - INFECTIOUS MYXOMATOSIS OF RABBITS : OBSERVATIONS ON THE PATHOLOGICAL CHANGES
      INDUCED BY VIRUS MYXOMATOSUM (SANARELLI).
AB  - The virus of infectious myxomatosis of rabbits (Sanarelli) induces multiple
      lesions in the skin, lymph glands, tunica vaginalis,epididymis, testicle, spleen,
      and lungs. Growth and destruction of cells in the epidermis overlying the
      myxomatous masses leads to the formation of vesicles. Cytoplasmic inclusions are
      found in affected epidermal cells. Occasionally, similar inclusions are seen in
      other involved epithelial cells. The nature of the inclusions is an open
      question. In the myxomatous masses situated in the subcutaneous and other
      tissues, evidences of alteration and growth of certain cells are observed.

PMID- 19869742
TI  - REACTIONS OF RABBITS TO NON-HEMOLYTIC STREPTOCOCCI : III. A STUDY OF MODES OF
      SENSITIZATION.
AB  - The most satisfactory method thus far found for the induction and maintenance of
      a high degree of hypersensitiveness-"allergy," "hyperergy"-against non-hemolytic
      streptococci consists in the repeated production of small focal lesions with
      minimal doses of bacteria. After a preliminary sensitizing period of about 2
      weeks' duration with either large initial, or small multiple daily inoculations,
      the later foci need be produced only at 7 to 10 day intervals. Chronicity of low
      grade infection appears to be an important factor in the attainment of a high
      degree of hypersensitiveness.

PMID- 19869743
TI  - THE BLOOD CHEMISTRY OF AN ACUTE TRYPANOSOME INFECTION.
AB  - The CO(2) capacity of the serum is markedly lowered early in infection with
      Trypanosoma equiperdum. The non-protein nitrogen and uric acid constituents of
      the blood are increased in the terminal stages. The kidneys also show terminal
      degenerative changes. The cholesterol remains unchanged throughout. Lecithin is
      markedly increased, most of the observations showing a 20 per cent to 50 per cent
      rise in this substance. Liver glycogen is lower than normal in the early stages
      and could not be demonstrated in the later stages of the infection. The blood
      sugar remains normal until a very late period in the disease.

PMID- 19869744
TI  - THE SURVIVAL OF YELLOW FEVER VIRUS IN CULTURES.
AB  - 1. The virus of yellow fever has been found to survive in artificial culture
      media for at least 12 days at a temperature of 35 degrees C. No visible growth
      has been present and no reproduction of the virus has been demonstrated. 2.
      Infections have been obtained in rhesus monkeys with two strains of virus in
      quantities as small as 0.00001 cc. of infectious blood, and with one strain in an
      amount probably as minute as 0.000001 cc.

PMID- 19869745
TI  - STUDIES ON BARTONELLA MURIS ANEMIA OF ALBINO RATS : I. TRYPANOSOMA LEWISI
      INFECTION IN NORMAL ALBINO RATS ASSOCIATED WITH BARTONELLA MURIS ANEMIA II.
      LATENT INFECTION IN ADULT NORMAL RATS.
AB  - 1. The virus of Bartonella muris anemia of splenectomized rats may be transmitted
      to normal young unoperated rats and rabbits. This confirms the observations of
      Ford and Eliot. 2. Trypanosoma lewisi infections in normal adult rats are
      accompanied by an anemia most marked at the height of the infection and the
      appearance of Bartonella muris bodies in the red blood cells. 3. In young rats
      Trypanosoma lewisi may produce death from the severity of the anemia,
      complicating the disease. The anemic virus may be separated from the Trypanosoma
      lewisi infected blood by passage through young rabbits with subsequent
      maintenance of the strain in immature rats. 4. A strain of the virus of
      Bartonella muris anemia capable of producing an anemia in young rabbits and young
      rats for successive transfers has been isolated from the blood of normal adult
      unoperated rats by passage through young rabbits. 5. The adult normal rat is a
      carrier of the Bartonella muris virus. 6. Splenectomy in young suckling rats
      separated from the mother is not followed by a Bartonella muris anemia. The young
      suckling rat is not a carrier of the infection.

PMID- 19869746
TI  - STUDIES ON BARTONELLA MURIS ANEMIA OF ALBINO RATS : III. THE PROTECTIVE EFFECT OF
      AUTOPLASTIC SPLENIC TRANSPLANTS ON THE BARTONELLA MURIS ANEMIA OF SPLENECTOMIZED
      RATS.
AB  - Autoplastic splenic transplants were made in adult albino rats 4 weeks and 7
      weeks prior to splenectomy and the protective effects against infection with the
      Bartonella muris anemia observed. 1. One-fourth of the spleen left in situ will
      protect adult albino rats against the Bartonella muris anemia. 2.
      Autotransplantation of splenic tissue in adult rats is successful in over 90 per
      cent of instances. 3. Autoplastic splenic transplants performed 7 weeks prior to
      splenectomy afford protection against Bartonella muris anemia in more than 50 per
      cent of instances, whereas 4 week old transplants do not protect. 4. A
      comparative histological study of the transplants of protected and unprotected
      rats reveals a regeneration of the pulp cells in the protected rats and an
      exhaustion destruction of the pulp in the unprotected rats. 5. The reticular
      cells play a specific role in protecting the adult albino rat against Bartonella
      muris anemia.

PMID- 19869747
TI  - STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : II. CONSECUTIVE ERYTHROCYTE AND
      HEMOGLOBIN OBSERVATIONS ON GROUPS OF NORMAL RABBITS.
AB  - Observations are reported on the consecutive weekly erythrocyte counts and the
      hemoglobin contents of the peripheral blood in 5 groups of normal rabbits,
      comprising 45 animals, during a period of 20 months from October, 1927 to July,
      1929. The duration of individual group examinations varied from 8 to 35 weeks.
      The results are analyzed on the basis of the weekly mean values of each group. On
      the whole, the erythrocyte values were quite uniform within a narrow range of
      variation, while the hemoglobin content was comparatively irregular within a
      wider range of variation. The major changes in the levels of mean values of both
      the red cells and the hemoglobin, however, were found to be statistically
      significant. The directions or trends in the levels of the erythrocyte and
      hemoglobin mean values did not necessarily move in opposite directions. The
      general levels of the erythrocyte and hemoglobin mean values were not identical
      for two consecutive years, those of 1927-28 being higher than those of 1928-29.
      The fluctuations of both red cell and hemoglobin mean values observed in one
      group of animals were also usually observed in another group examined during the
      same months.

PMID- 19869748
TI  - STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : III. CONSECUTIVE TOTAL WHITE BLOOD
      CELL OBSERVATIONS ON GROUPS OF NORMAL RABBITS.
AB  - Consecutive weekly observations on the total white cell count of the peripheral
      blood were made on 5 groups of normal rabbits, a total of 45 animals, during a
      period of 20 months from October, 1927 to July, 1929. The duration of individual
      group examinations varied from 8 to 35 weeks. In the case of 4 groups followed 13
      to 35 weeks, the general trend of the total white cell means was toward
      increasing values; with the group followed 8 weeks, the means were maintained at
      a constant level. The changes in the levels of the granular cell means were
      usually accompanied by changes in a similar direction of the non-granular cell
      means. In the case of 3 of the 4 groups followed for the longest periods, the
      greatest relative alterations occurred in the non-granular cells. The
      fluctuations in the mean values of the total white cells and of the granular and
      the non-granular cells which were observed in one group of rabbits, were also
      generally observed in another group examined during the same months. The period
      of greatest irregularity in the mean values of the total white cell means and of
      the granular and the non-granular cell means as well, occurred during the late
      winter and spring months of both years. The general level of the total white cell
      mean values in the groups examined during 1927-28 was higher than that of the
      groups observed during 1928-29. A similar difference was found in the granular
      and non-granular mean values but it was somewhat less marked in the case of the
      granular cells.

PMID- 19869749
TI  - TOOTH GROWTH IN EXPERIMENTAL SCURVY.
AB  - 1. The incisor teeth of guinea pigs have a constant rate of growth in health. 2.
      Deprivation of Vitamin C causes the teeth to cease growing. Readministration of
      the vitamin restores the growth. 3. Administration of small amounts of
      antiscorbutic substance results in rates of growth roughly proportional to
      dosage. 4. Under standard experimental conditions used in the testing of
      foodstuffs for antiscorbutic value, the rate of tooth growth would appear to be a
      precise indication of the degree of scurvy, being more delicate than the Sherman
      score, and more constant as well as more simple, than the Hojer method. 5. Stress
      in terms of usage appears to exaggerate the scorbutic lesions in the teeth.

PMID- 19869750
TI  - STUDIES ON THE BLOOD VESSELS IN THE MEMBRANES OF CHICK EMBRYOS : PART I. ABSENCE
      OF NERVES IN THE VASCULAR MEMBRANE.
AB  - THE AGREEMENT OF PHYSIOLOGICAL EXPERIMENT WITH ANATOMICAL FINDINGS JUSTIFIES OUR
      CONCLUSION: the blood vessels of the vascular membrane of chick embryos do not
      contain nerves.

PMID- 19869751
TI  - STUDIES ON THE BLOOD VESSELS IN THE MEMBRANES OF CHICK EMBRYOS : PART II.
      REACTIONS OF THE BLOOD VESSELS IN THE VASCULAR MEMBRANES.
AB  - A comparison of the effect of stimulation upon the arterial subdivisions shows
      that these differ in irritability. The capillaries are most irritable, then come
      the small arterial branches, and last the main stems of arteries, these being the
      least irritable. The non-innervated blood vessels of the vascular membranes
      exhibit therefore the behavior described by G. Ricker in the case of those which
      have a nervous apparatus. We have demonstrated accordingly similar properties in
      vessels which are not innervated as in those which are. Certain differences exist
      however. The action of adrenalin on the vessels of the vascular membrane is
      inconstant and certain other substances are wholly ineffective. Ricker's
      experiments have advanced knowledge on the regularity of the vascular reactions
      and have paved the way for these experiments of ours. The result of our
      experiments with vessels free of nerves suggests that a reexamination may be
      fruitful of the mechanism which obtains in innervated vessels. There can be no
      doubt that nerves play a role in the behavior of vessels; it appears now to be
      necessary to define more accurately precisely what this is.

PMID- 19869752
TI  - STUDIES ON THE BLOOD VESSELS IN THE MEMBRANES OF CHICK EMBRYOS : PART III.
      ANATOMY AND PHYSIOLOGY OF THE BLOOD VESSELS AT DIFFERENT AGES.
AB  - On the basis of the anatomical studies presented the following inferences or
      conclusions are drawn. 1. In the course of development there appear in the
      vascular membranes of chick embryos arterial vessels of all calibers, namely,
      capillaries, small arteries with 2 or 3 cell layers, and large arteries formed of
      endothelium, longitudinal and circular layers of muscle and adventitia. 2. In
      none of the stages are elastic fibers developed. Only in the most central portion
      of the umbilical artery, in that portion namely which is to be regarded as
      belonging to the embryo, are elastic fibers discoverable. 3. The structure of
      capillaries is histologically the same at all stages. The small arteries of
      embryos 10 days old resemble histologically those of 18. At no stage of
      development are appearances of degeneration nor of fat to be found in arteries.
      When the physiological results of our investigations are compared with the
      anatomical ones the following comments may be made. In respect to Paragraph 1 of
      the anatomical results we may remark that when we study the different forms of
      the wall of arterial vessels the most delicate vessels consisting of single cells
      exhibit the greatest irritability. Those which are built of 3 to 4 muscle layers
      are less irritable. Stouter vessels appearing for the first time at 10 days of
      incubation require stronger stimuli to bring about the same reaction. In respect
      to Paragraph 2 of the anatomical results we may make this comment. The absence of
      elastic fibers in all arteries of the embryonic membranes throughout the period
      of their development is important in defining a physiological property of the
      larger vessels. The medium and larger vessels, beginning with the 4th day of
      incubation, contract differently from normal adult human arteries. In the
      contracted state they appear in cross section not as small replicas of larger
      circular structures, but take on a new form. During the course of contraction
      they become flat and appear band-like as would a garden hose when it is
      compressed by a weight. In examining a vessel so contracted one sees on rotating
      the vessel either a broad side or a narrow one. It is for this reason that such
      arteries appear alternately narrow as a line or broad as a band. It is not until
      the narrow artery is elevated with a hook that its uniform band-like nature
      becomes evident. The absence of elastic tissue, the presence of which in all
      probability is mainly responsible for the usual shape of arteries on cross
      section, permits one to see how the phenomenon which has been described may come
      about. Concerning Paragraph 3 of the anatomical conclusions we have this to say.
      According to the histological investigation a stage of degeneration is wanting in
      the blood vessels of the embryonic membrane in a sense in which one is accustomed
      to see such changes in other blood vessel systems during the course of life. On
      the day of hatching the constituent cells and fibers of the arteries of all
      calibers are anatomically the same as in their early development. These vessels
      do not die as the result of aging: The nutrient fluid ceases to flow because of
      contraction of the umbilical vessels. The blood vessels die in complete
      possession of their physiological irritability and anatomical integrity. The
      unaltered irritability of blood vessels of the same caliber at all ages is
      consonant with their unaltered anatomical structure.

PMID- 19869753
TI  - STUDIES ON THE BLOOD VESSELS IN THE MEMBRANES OF CHICK EMBRYOS : PART IV.
      MODIFICATION OF IRRITABILITY OF THE BLOOD VESSELS.
AB  - When faradic stimulation was undertaken of vessels irrigated with Ringer's
      solution, which alternately contained and was free from carbon dioxide, it was
      observed that the reaction was far less when the solution contained carbon
      dioxide. A reversal of the effect could be obtained many times. It appears,
      therefore, that when Ringer's solution contained carbon dioxide in the
      concentration described, the irritability of the vessels to electrical stimuli
      decreased, although carbon dioxide by itself and in the absence of the
      application of the stimuli, appeared to be void of effect upon the vessels. The
      rare, divergent results were traced to technical errors. We attempted to discover
      whether the observed decrease in irritability of the vessels might not be due to
      the absence of oxygen. For this purpose we irrigated the vessels with Ringer's
      solution alternately containing nitrogen and oxygen. When nitrogen caused any
      change this was due to an influence on the rate of the heart and not on the
      irritability or reactivity of the arteries. In whatever way we tried we were
      unable to bring about a change in reactivity of the arteries by creating a
      condition of oxygen lack independently of a change in the rate of the heart beat.
      We attempted to study also the effect of other acids beside carbon dioxide on the
      changed reactivity of the arteries. Irrigation with various concentrations of
      lactic acid was without result. We also employed solutions buffered with
      potassium and sodium phosphate. When the irrigation was undertaken with these
      solutions having a pH range varying from 7.7 to 5.9 we observed neither a direct
      action nor one which modified the preparation in such a way as to change its
      susceptibility to faradic stimulation. Important investigations have been
      published recently by Atzler and Lehmann (2) on the direct influence of the
      hydrogen ion concentration on the behavior of blood vessels. Hammett and Zoll
      believed that, as the result of their experiments in which they attempted to
      bring about stimulation with solutions of concentrated carbon dioxide, they were
      able to exclude the possibility of action due to acid alone and therefore
      ascribed to carbon dioxide a specific effect. In our own experiments the method
      of irrigation does not permit an inference whether, or how far, an acid effect
      plays a role in the carbon dioxide experiments. For beside the question of
      hydrogen ion concentration and of buffering, the question of the penetration of
      substances from the surface to the contractile elements of the wall of the
      vessels requires to be considered. Carbon dioxide has an ability, beyond that of
      all other substances, to penetrate through tissues (3). It may be owing to this
      property that we could influence the reactivity of the blood vessels with it and
      it alone. This possibility must be further investigated. In these experiments,
      however, it was our object to show only that it was possible to influence the
      irritability of blood vessels experimentally. The conclusion is justified by our
      experiments that carbon dioxide in small concentrations reduces the threshold of
      irritability for electrical stimuli of the blood vessels of the embryonic
      membrane.

PMID- 19869754
TI  - ENHANCED PASSIVE IMMUNITY TO STREPTOCOCCUS INFECTION IN RABBITS.
AB  - The experimental work herein reported tends to justify our hypothesis recently
      expressed, that the common failure of antibacterial serums to combat active
      infections when passively transferred to a normal animal, is due not so much to a
      lack of suitable or sufficient antibodies as to absence of cell preparation or
      mobilization in the recipient. In the case of experimental streptococcus empyema
      in the rabbit the course of the ordinarily fatal infection is in no wise affected
      by the transfer of the pleural fluid containing large numbers of mononuclear
      cells derived from an animal that is itself protected as a result of a non
      specific irritation. The serum of a rabbit highly immunized against the
      streptococcus and containing antibodies for it, produces relatively slight effect
      in prevention or cure. In contrast to this the pleural exudate, either acute
      (polymorphonuclear) or subacute (mononuclear), produced in an actively immunized
      animal does protect passively to a considerable degree. In a similar fashion
      normal exudate cells of either type in combination with the relatively
      ineffective antiserum give a high degree of protection. It remains for further
      analysis to determine whether this form of passive immunity by antiserum enhanced
      by the addition of cells depends on the vital properties of the cells transferred
      or on their stimulation to cell mobilization in the recipient. And furthermore
      the extent to which this enhanced passive immunity may be effective in cure, and
      whether the cure is applicable to local or to both local and generalized
      infection remains to be seen.

PMID- 19869755
TI  - STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : IV. CONSECUTIVE NEUTROPHILE,
      BASOPHILE, AND EOSINOPHILE OBSERVATIONS ON GROUPS OF NORMAL RABBITS.
AB  - Consecutive weekly observations on the neutrophile, the basophile, and the
      eosinophile counts of the peripheral blood were made on 5 groups of normal
      rabbits, a total of 45 animals, during a period of 20 months from October, 1927
      to July, 1929. Individual groups were examined 8 to 35 weeks. In the case of the
      4 groups followed 13 to 35 weeks, the general trend of the neutrophile cells was
      towards increased mean values; with the group followed 8 weeks, decreasing values
      were found. An increase in the mean values of the basophile cells was observed in
      the two groups of rabbits followed in 1927-28; in the groups of 1928-29, the mean
      values decreased. The mean values of the eosinophile cells showed no definite
      trends but the findings were characterized by abrupt and marked fluctuations. The
      periods of greatest irregularity in mean neutrophile and eosinophile values
      occurred in the fall and the late winter and spring months of both years, but in
      the case of the basophiles, the irregularities were distributed throughout the
      first year and occurred chiefly in the winter months of the second year. The
      major trends and many of the minor fluctuations as well which were observed in
      the mean cell values of one group of rabbits were also generally seen in another
      group examined during the same months. The general levels of the neutrophile, the
      basophile, and the eosinophile mean values in the groups examined during 1927-28
      were higher than in the groups of 1928-29.

PMID- 19869756
TI  - STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : V. CONSECUTIVE LYMPHOCYTE AND
      MONOCYTE OBSERVATIONS ON GROUPS OF NORMAL RABBITS.
AB  - Consecutive weekly observations on the lymphocyte and monocyte counts of the
      peripheral blood were made on 5 groups of normal rabbits, a total of 45 animals,
      during a period of 20 months from October, 1927 to July, 1929. Individual groups
      were examined 8 to 35 weeks. The results are analyzed on the basis of the mean
      group values of each week. In the case of the 4 groups followed 13 to 35 weeks,
      there was a general tendency for the lymphocyte mean values to become increased;
      with the group observed 8 weeks, the level of mean values showed little change.
      The general trend of the monocyte mean values was also in the direction of higher
      levels but it was less pronounced than that of the lymphocytes. The period of
      greatest irregularity in the mean values of the lymphocytes was in the late
      winter and spring months of both years. With the monocytes, periods of
      fluctuating values occurred in the fall of 1927, the spring and early summer of
      1928, and in the late winter, spring, and early summer of 1929. There was a
      certain degree of parallelism in the case of two groups examined during the same
      months with respect to the direction and time of occurrence of a change in the
      level of lymphocyte and monocyte mean values. The general levels of lymphocyte
      and monocyte mean values in the groups examined during 1927-28 were higher than
      in the groups of 1928-29. The results based upon the trends of mean group values
      obtained from consecutive weekly observations showed no evidence of a consistent
      numerical relationship between lymphocytes and monocytes.

PMID- 19869757
TI  - EXPERIMENTAL NEPHRITIS IN THE FROG : I. THE ANATOMICAL EVIDENCE OF DAMAGE.
AB  - 1. The damage produced by corrosive sublimate, potassium bichromate and uranium
      nitrate in the frog's kidney is described. 2. The morphological lesions consist
      of evidences of tubular damage, such as regressive changes in the epithelium, and
      of damage to the glomeruli ranging from increase in their permeability to gross
      damage of and hemorrhage from the tuft. 3. The point is emphasized that these
      lesions differ in their degree rather than in their nature from those found in
      the mammalian kidney after the administration of the same poisons. 4. The frog's
      kidney is exceptionally well suited therefore for the study of lesions which
      though present are masked in the complexities of structure and function of the
      mammalian kidney.

PMID- 19869758
TI  - A STUDY OF THE RELATIONSHIP OF THE SCROTAL SWELLING AND RICKETTSIA BODIES TO
      MEXICAN TYPHUS FEVER.
AB  - THE EXPERIMENTS RECORDED ABOVE HAVE DEMONSTRATED THE FOLLOWING POINTS: 1. Scrotal
      swelling can appear in guinea pigs directly inoculated from a human case of
      Mexican typhus fever. 2. In certain strains of this disease, a number of
      generations of guinea pigs may show absolutely no scrotal swelling, which,
      however, may reappear in subsequent animals, suggesting-though not absolutely
      proving-that the scrotal swelling is an integral part of the disease and is not
      due to an incidental accompanying organism. If the latter were true, one would
      expect the organisms that caused the scrotal swelling to disappear during the
      negative generations. 3. A typhus fever sustained by a guinea pig without scrotal
      swelling protects against the swelling upon subsequent inoculation with a strain
      which produces this with considerable regularity. 4. Louse passage increases the
      capacity of a strain to produce the scrotal lesion, probably because of the
      considerable accumulation of rickettsia in the louse, but in the experiment
      noted, even after louse passage, two generations without swelling occurred,
      followed by reoccurrence of the swelling. We believe that these observations,
      taken together, can be interpreted in favour of the likelihood that the swelling
      is a part of the disease and that the rickettsia-like organisms described by
      Mooser in the tunica vaginalis have etiological significance.

PMID- 19869759
TI  - STUDIES ON INFLAMMATION : IV. FIXATION OF FOREIGN PROTEIN AT SITE OF
      INFLAMMATION.
AB  - Foreign protein such as horse serum injected into an inflamed peritoneal cavity
      penetrates into the blood stream less rapidly than when introduced into the
      normal cavity. Foreign protein injected into a cutaneous inflammatory area is
      held in situ for a longer period than when injected into an inflamed peritoneal
      cavity. Foreign protein introduced into the circulating blood stream accumulates
      in an inflamed area, where it is found in greater concentration than in normal
      tissue. Accumulation of foreign protein at the site of inflammation explains the
      phenomenon of local anaphylaxis described by Auer in rabbits sensitized to horse
      serum. The antigen accumulating in the inflamed ear reacts with antibody,
      intensifies a pre-existing inflammatory reaction and produces necrosis of the
      ear.

PMID- 19869760
TI  - SUSCEPTIBILITY OF RABBITS TO INFECTION BY THE INHALATION OF TYPE II PNEUMOCOCCI.
AB  - 1. The susceptibility of rabbits to inhalations of pneumococci varies in direct
      proportion to the virulence of the organism for rabbits. 2. When rabbits are
      exposed to a pneumococcus spray, irrespective of the virulence of the organism,
      the bacteria readily penetrate into the lower respiratory tract. 3. When rabbits
      are exposed to a spray of avirulent degenerated "R" form of pneumococcus,
      septicemia does not occur and pneumococci are seldom recovered from the liver,
      kidney or spleen. 4. When rabbits are exposed to a spray of slightly virulent
      Pneumococcus Type II (SAv) a non-fatal septicemia may occur and pneumococci may
      be recovered from the liver, kidney and spleen. 5. When rabbits are exposed to a
      spray of virulent Type II (Sv) pneumococci, septicemia may occur which in certain
      instances terminates fatally. Pneumococci may also be recovered from the liver,
      kidney and spleen.

PMID- 19869761
TI  - DEVELOPMENT OF AGGLUTININS AND PROTECTIVE ANTIBODIES IN RABBITS, AFTER INHALATION
      OF TYPE II PNEUMOCOCCI.
AB  - 1. Following repeated inhalations of the degenerated non-virulent "R" forms of
      Type II pneumococcus, no type specific antibodies can be demonstrated in the
      serum of rabbits. 2. Following repeated inhalations of slightly virulent Type II
      (SAv) pneumococci, only protective antibodies can be demonstrated in the serum of
      rabbits. 3. Following repeated inhalations of virulent Type II (Sv) pneumococci,
      agglutinins and protective antibodies can be demonstrated in the serum of
      rabbits. 4. Following repeated exposures of rabbits to inhalation of pneumococci,
      the type specific response, evidenced by type specific protective antibodies and
      agglutinins, varies in direct proportion to the virulence of the culture used.

PMID- 19869762
TI  - A TYPE SPECIFIC SUBSTANCE DISTINCT FROM THE SPECIFIC CARBOHYDRATE IN PNEUMOCOCCUS
      TYPE I.
AB  - 1. Evidence has been presented for the existence of a substance distinct from the
      specific carbohydrate in the autolytic products of Pneumococcus Type I. 2. The
      substance reacts specifically by precipitating homologous antiserum which either
      occurs naturally without antibody against the specific carbohydrate or has been
      deprived of that antibody artificially. 3. In guinea pigs passively sensitized
      with such antisera the homologous autolysate containing the substance alone
      produces typical lethal anaphylactic shock. 4. In weakly alkaline solution the
      substance is destroyed by boiling. In weakly acid solution it resists a
      temperature of 100 degrees C. for at least (1/2) hour. Autoclaving for 1 hour at
      15 pounds pressure in either acid or alkaline solution destroys its activity as
      precipitinogen. 5. The substance is resistant to peptic digestion. 6. The
      chemical nature and the possible identification of the substance as a haptene
      have been discussed.

PMID- 19869763
TI  - THE INFLUENCE OF ULTRA-VIOLET RADIATION ON THE WEIGHT OF ADULT RABBITS, NORMAL
      AND SYPHILITIC.
AB  - In summarizing the results obtained for these 6 groups of animals, the following
      conclusions may be drawn: Normal rabbits living in total darkness and exposed to
      ultra-violet radiation at regular intervals showed a more rapid rate of increase
      in weight than animals living under the same condition, but after an initial
      period of rapid increase, the irradiated animals maintained a lower body weight
      than those living in the dark. Under the same conditions, animals inoculated with
      T. pallidum and exposed to ultra-violet light maintained a lower weight than the
      corresponding control groups living in total darkness. Furthermore, the mortality
      rate from pneumonic infection was found to be greater in animals exposed to ultra
      violet radiation than in those living entirely in the dark. It is evident,
      therefore, that, under the conditions given, ultra-violet radiation was
      detrimental rather than beneficial.

PMID- 19869764
TI  - A STUDY OF THE RESISTANCE OF NORMAL HUMAN BEINGS TO RECENTLY ISOLATED STRAINS OF
      PATHOGENIC PNEUMOCOCCI.
AB  - With a view to obtaining information as to the virulence of pneumococci for human
      beings a study was made of the pneumococcidal action of normal human serum
      leucocyte mixtures for freshly isolated strains of pathogenic pneumococci. It was
      found that human beings as a group showed well marked pneumococcus destroying
      power in their blood for all types of organisms studied. Individuals, however,
      exhibited wide variations in their reactions against the different types. These
      ranged from marked killing effect for one type of pneumococcus to none or slight
      against another. While reactions against different strains within the type often
      varied considerably this difference was less, on the whole, than that between
      types. An interpretation of these findings in the light of previous animal
      experiments in which actual determination of resistance to pneumococcus infection
      was made leads to the inference that human beings in general possess a
      considerable degree of natural immunity to all types of pneumococci but that
      individuals may be relatively susceptible to one or more types and at the same
      time resistant to others; also that pathogenic strains of pneumococci vary much
      in their virulence for man.

PMID- 19869765
TI  - THE ORIGIN AND FATE OF TWO TYPES OF MULTI-NUCLEATED GIANT CELLS IN THE
      CIRCULATING BLOOD.
AB  - 1. It has been demonstrated that giant cells of the foreign body and epithelioid
      types can be induced to appear in the blood stream. 2. Evidence has been
      presented which indicates that foreign body giant cells are primarily formed by
      fusion of monocytes and that the fate of these giant cells is accomplished, at
      least in some instances, by a separation into the constituent elements. 3.
      Further evidence has been presented which lends support to the hypothesis that
      "epithelioid giant cells" reach their stage of evolution, not by fusion of
      monocytes, but by amitotic division of the nuclei of monocytes and epithelioid
      cells. 4. The presence of giant cells in the peripheral blood as the result of
      agar injections is almost invariably associated with, or preceded by a marked
      monocytosis in which the new monocytes are of large size and show evidence of
      immaturity. 5. Injections of agar into the tissues result in decreased absolute
      and percentage values of lymphocytes and a diminution of the specific granules in
      many of the polymorphonuclear leucocytes. 6. It would appear from these studies
      that a clear differentiation of "epithelioid giant cells" and "foreign body giant
      cells" in the blood is usually possible, but that on the other hand, a few cells
      may be present which have some of the characteristics of each type. These latter
      cells probably represent in their formation both a fusion of individual cells and
      an amitotic division of the nuclei of monocytes. 7. Clasmatocytes or macrophages
      have in rare instances been seen to take part in the formation of foreign body
      giant cells. At least one instance has been noted of the fusion of a clasmatocyte
      with several monocytes. No evidence is available to demonstrate that macrophages
      ever play a part in the formation of "epithelioid giant cells."

PMID- 19869766
TI  - ON THE MECHANISM OF OPSONIN AND BACTERIOTROPIN ACTION : V. EXPERIMENTAL TEST OF A
      THEORY OF TROPIN ACTION.
AB  - Antisera against several strains of acid-fast bacteria have been separated into
      their euglobulin, pseudoglobulin and albumin fractions. The globulin fractions
      have been found to possess the essential properties of bacteriotropic sera: thus
      they alter the bacterial surface properties, and, in quantitative correspondence,
      cause agglutination and phagocytosis; these several effects withstand washing of
      the sensitized bacteria; the effects are little if at all affected by
      inactivation of the antisera before fractionation; the combination of antibody
      and antigen is serologically specific. The conclusion is drawn that the contact
      of antigen with fresh homologous immune serum results in the deposit on the
      antigen surface of a substance or substances contained in the globulin fractions
      of the antiserum; as a consequence of this surface deposit leucocytes can spread
      upon and engulf the antigen.

PMID- 19869767
TI  - ON THE MECHANISM OF OPSONIN AND BACTERIOTROPIN ACTION : VI. AGGLUTINATION AND
      TROPIN ACTION BY PRECIPITIN SERA. CHARACTERIZATION OF THE SENSITIZED SURFACE.
AB  - As a further test of the theory of tropin action proposed in the preceding paper
      artificial surfaces have been prepared, and have been found to be phagocytized
      according to prediction from the theory. Protein was adsorbed on collodion
      particles according to the technique of F. S. Jones. These particles were then
      agglutinated and prepared for phagocytosis by the corresponding protein
      precipitin sera. The precipitating, agglutinating, surface and tropin effects for
      each serum or serum globulin fraction have been found to be in satisfactory
      quantitative correspondence. All of these effects were serologically specific;
      all remained almost unaffected by inactivation of the immune sera for 30 minutes
      at 56 degrees C. or by washing of the particles after sensitization. The surfaces
      of particles maximally sensitized by homologous rabbit immune serum or one of its
      globulin fractions have shown certain characteristic properties, i.e., they were
      cohesive, had wetting properties characteristic for protein, and were isoelectric
      at pH. 5.5 to 5.8. The same set of properties were found for immune precipitate
      in the zone of maximal precipitation. The same properties have also been found
      for maximally sensitized acid-fast bacteria, and for maximally sensitized sheep
      erythrocytes. These results indicate, we believe, that precipitation,
      agglutination, the surface changes and increased phagocytosis are all
      consequences of one underlying phenomenon. This phenomenon is the specific
      chemcal combination with, and deposit on the surface of the antigen of antibody
      protein. The several serological reactions then follow as consequences of the
      properties of the sensitized surface and of the special environing conditions.
      The antibody is contained in the globulin fractions of immune serum, and appears
      to be a globulin with physico-chemical differences from normal serum globulin.

PMID- 19869768
TI  - THE BACTERIOSTATIC ACTION OF CERTAIN COMPONENTS OF COMMERCIAL PEPTONES AS
      AFFECTED BY CONDITIONS OF OXIDATION AND REDUCTION.
AB  - There are present in commercial peptones substances which exhibit bacteriostatic
      properties for certain bacterial species. These substances are bacteriostatic in
      the oxidized form, but not in the reduced form. Their bacteriostatic action can
      be overcome, and their concentration titrated, by the addition of reduced thiol
      compounds to the media in which they are present. Different brands of peptone
      differ greatly in the amount of bacteriostatic substances they contain; these
      differences account, in part at least, for the fact that media prepared from the
      same meat infusion, but with different kinds of peptone, vary in their ability to
      support bacterial growth. The bacteriostatic fraction of a certain peptone
      solution can be completely removed by precipitation with acid and acetone. A
      peptone which has thus been purified becomes capable of supporting the growth of
      very small inocula of Pneumococcus. The significance of the sensitiveness of
      certain bacterial species to substances which are bacteriostatic in the oxidized
      but not in the reduced form is considered with reference to (a) the mechanism of
      bacteriostasis, (b) the growth of bacterial species in artificial media, (c) the
      problem of infection.

PMID- 19869769
TI  - EXPERIMENTS ON ANAPHYLAXIS TO AZOPROTEINS : THIRD PAPER.
AB  - Experiments with azoproteins containing stereo-chemical isomeric groups of d- and
      l-tartaric acid showed well marked specificity of the anaphylactic reaction to
      these antigens, in conformity with the results of precipitin tests. Shock in
      these animals could be prevented by injection of azodye containing the specific
      groups. This phenomenon is ascribed to a desensitization.

PMID- 19869770
TI  - SURVIVAL AND MULTIPLICATION OF THE VIRUS OF POLIOMYELITIS IN VITRO.
AB  - The study here reported concerns attempts at bacteriological cultivations with
      fragments of brain or cord, or with Berkefeld V filtrates of the nervous tissues,
      from seven monkeys successfully inoculated with poliomyelitic virus. With these
      materials, 315 tubes were inoculated, of which thirty-six showed minute bodies
      resembling the globoid bodies described by Flexner and Noguchi. However, a study
      of subplants from these minute, morphological particles did not convince us that
      we had in hand actual cultures of the globoid bodies, or indeed of any living
      microorganism. Nevertheless, when washed sediments from subplants of one of the
      strains, representing the seventh, eighth, ninth, and tenth transfers, were
      inoculated into monkeys, the clinical signs and pathological effects
      characteristic of experimental poliomyelitis could be induced. The virulence of
      the "cultures" could not be ascribed to carrying over the original material into
      these remote subplants since the seventh transfer represented a dilution of the
      original cultivated material to about 1.5 x 10(-12), and the tenth, to about 1.3
      x 10(-18) if one assume, as the transfer technic justifies, a thorough mixing of
      the contents of each tube. On the contrary, it appears as if the poliomyelitic
      virus had multiplied in vitro, and had increased as a consequence of being in a
      medium of a modified living tissue-cell culture. For in practically all specimens
      we observed many well-preserved kidney tissue cells and leucocytes, the latter
      probably derived from human ascitic fluid, a component of the Smith-Noguchi
      medium. In this connection, it should be mentioned that the several lots of
      ascitic fluid used in the cultivation tests were recently obtained from patients
      and employed from a week to a month after their collection. There remains for
      consideration the problem of the selective pathogenicity of the "cultures:" only
      the material of those tubes of the ninth and tenth transfers which showed the
      "globoid bodies" proved pathogenic; those respective tubes of the same transfers
      which were free from the minute bodies but apparently identical in all other
      respects, were avirulent. It may be that the virus was adsorbed to the particular
      bodies which we have found in the "cultures" and which resemble closely the
      globoid bodies of Flexner and Noguchi. Further elaboration of this study would be
      necessary, however, before such an inference could be regarded as a definite
      hypothesis.

PMID- 19869771
TI  - A METHOD FOR SUPRAVITAL STAINING OF ANIMALS WITH NEUTRAL RED AND ITS PRESERVATION
      IN PARAFFIN SECTIONS.
AB  - A simple, rapid method for staining all the supravitally stainable cells in the
      body, as in supravital preparations with neutral red, is described, together with
      a method for faithful preservation of the dye in paraffin sections. The essential
      points of the technique are, first, to secure the reaction of cells to neutral
      red which corresponds to the so-called supravital technique, involving the
      reaction of only those substances which respond to the dye while the cell is
      living; and second, to preserve the stain through the processes of fixation,
      embedding, and counterstaining.

PMID- 19869772
TI  - THE ORIGIN OF MONOCYTES IN CERTAIN LYMPH NODES AND THEIR GENETIC RELATION TO
      OTHER CONNECTIVE TISSUE CELLS.
AB  - 1. The theories for the origin of monocytes from myeloblasts, lymphocytes,
      endothelium, macrophages, and primitive cells are reviewed and considered. 2.
      Monocytes in all stages of development have been demonstrated to be present
      constantly in large numbers in all the lymph nodes of the body, except in the
      large mesenteric group. 3. The relations of these cells to undifferentiated
      cells, lymphocytes, macrophages, plasma cells, and endothelium are described. 4.
      The origin of adult monocytes from primitive undifferentiated cells through the
      stages of monoblasts and pre-monocytes is described and illustrated. 5. The
      demonstration in certain lymph nodes of innumerable monocytes in all stages of
      development permits of a shifting of the term "monoblast" from a more or less
      theoretical name to its proper place as a term designating that particular cell
      which is derived from a primitive undifferentiated cell and which is the
      immediate precursor of the pre-monocyte. 6. The term "pre-monocyte" is proposed
      to designate the intermediate stage between the monoblast and the mature
      monocyte. 7. Evidence is advanced to show that monocytes are an independent
      strain of cells, but that under physiological conditions they may be transformed
      into macrophages, this representing at least one way in which the latter cells
      normally are produced. 8. In no organs or tissues other than in certain specific
      lymph nodes, chiefly the peripheral group, can one constantly find monocytes in
      all stages of development. 9. Developing monocytes occasionally may be found in
      small numbers in the spleen, mesenteric lymph nodes, Peyer's patches,
      subcutaneous connective tissues, lungs, and omenta of normal rabbits, but their
      presence is by no means constant and their numbers are insignificant in
      comparison with those found in the peripheral lymph nodes. 10. Monocytes and pre
      monocytes do not stain by the common methods used for the demonstration of the
      reticulo-endothelial system and therefore must be considered for the present as
      independent of this system, except in so far as monocytes may be transformed into
      macrophages. 11. Plasma cells, stained with the supravital technique, as seen in
      lymph nodes, are described. No basis has been found for the theory that plasma
      cells and monocytes are closely related structural elements.

PMID- 19869773
TI  - THE SUSCEPTIBILITY OF MARMOSETS TO YELLOW FEVER VIRUS.
AB  - 1. It has been possible to introduce yellow fever virus into the small Brazilian
      monkeys, Callithrix albicollis and Leontocebus ursulus, by the bites of infected
      mosquitoes and to carry the virus through a series of four passages in each
      species and back to rhesus monkeys by the bites of Stegomyia mosquitoes fed on
      the last marmoset of each series. 2. Five specimens of L. ursulus were used. Four
      developed fever, and all died during the experiments. At least two showed liver
      necroses comparable to those found in human beings and rhesus monkeys that died
      of yellow fever. 3. Twenty specimens of C. albicollis were used. Very few showed
      a temperature reaction following the introduction of virus. Of those that died,
      none had lesions typical of yellow fever as seen in certain other species of
      monkeys and in humans. 4. The convalescent serum from each of five C. albicollis
      protected a rhesus monkey against yellow fever virus, but the serum from a normal
      marmoset of the same species was found to be non-protective.

PMID- 19869774
TI  - THE EXTRACTION OF THE CELL CONTENT OF MICRO-ORGANISMS BY PERCUSSION OF THE FROZEN
      CELLS.
AB  - A method is described for rapidly obtaining fresh extracts of microorganisms by
      percussion of the frozen cells. Filtrates giving the biuret reaction and yielding
      heavy precipitates upon the addition of acetic acid were obtained from the washed
      cells of cultures of yeast, hemolytic streptococcus, pneumococcus, B. coli, B.
      xerosis, B. dyphtheriae and the bacillus of bovine tuberculosis.

PMID- 19869775
TI  - THE RELATION OF NATURAL HUMORAL ANTIPNEUMOCOCCAL IMMUNITY TO THE INCEPTION OF
      LOBAR PNEUMONIA.
AB  - A study of the pneumococcidal-promoting action of the serum of lobar pneumonia
      patients, secured from 4 to 48 hours after the onset of the disease, has revealed
      the fact that in the majority of instances the serum possessed the power to
      promote killing of the homologous pneumococcus, isolated in different instances
      from the lung, blood, and sputum. While in some instances this action was slight,
      in others it was present to as great a degree as in normal individuals and
      persisted as long as 48 hours or more after the beginning of the disease. The
      variations observed from case to case were not related to the extent of the
      pneumonic lesion or to the virulence of the several pneumococcus strains but
      appeared to depend on differences in individual human beings in respect to the
      natural antipneumococcus properties of their blood and their reaction to the
      invading microorganism. A constant relationship was found to exist between the
      concentration of immune properties in the serum and blood invasion. In the
      presence of a well marked pneumococcidal-promoting power pneumococci were not
      found in the blood stream, and only when this property was greatly diminished or
      lost did blood invasion occur. The findings which are supported by certain
      previous experimental observations, indicate that lobar pneumonia can occur in
      the presence of a normal circulating antipneumococcus defense mechanism. From
      this it is inferred that before pneumococcus growth can be initiated there must
      be present in the lung local changes of such nature as to provide conditions for
      the multiplication of pneumococci protected from the pneumococcidal action of the
      blood. Suppositions as to the nature of these changes and the establishment of
      the pneumonic lesion are discussed.

PMID- 19869776
TI  - THE KILLING OF CERTAIN BACTERIA BY X-RAYS.
AB  - Both copper K X-rays and the soft general radiation from a tungsten tube operated
      at 12 KV kill B. coli and B. aertryke in a linearly exponential fashion. Within
      the experimental limits, the two organisms appear to be equally sensitive to
      these radiations. By making use of the fact that X-ray energy is absorbed in
      quanta, an approximate picture can be formed of the mechanism of this destructive
      action. If the average numbers of quanta (alpha) absorbed per bacterium per
      second are calculated from measurements of air ionization using the quantities
      outlined in the text, survival ratios for these bacilli can be approximately
      represented by the equations See PDF for Equation for filtered copper rays and
      See PDF for Equation for unfiltered copper rays (peak voltage = 34 KV). In terms
      of the foregoing interpretation this means that when death results, it is caused
      by the absorption of a single X-ray quantum of energy. Since only about one in
      twenty of the absorbed quanta kills, the sensitive cell constituents whose
      destruction leads to cell death must have a volume which is less than 0.06 of the
      bacterium itself.

PMID- 19869777
TI  - THE CATALYTIC EFFECT OF METHYLENE BLUE ON THE OXYGEN CONSUMPTION OF TUMORS AND
      NORMAL TISSUES.
AB  - 1. Methylene blue has no catalytic effect on the oxygen consumption of those
      normal adult tissues which do not possess aerobic glycolysis. The dye increases
      the oxygen consumption of these tissues when their respiration has been inhibited
      by the addition of KCN and their fermentative power thus brought into action. 2.
      Methylene blue increases the oxygen consumption of normal tissues having aerobic
      glycolysis, and of tumors. 3. The effect of methylene blue is roughly
      proportional to the fermentative power of tissues.

PMID- 19869778
TI  - IMMUNITY TO POLIOMYELITIS IN MOTHERS AND THE NEWBORN AS SHOWN BY THE
      NEUTRALIZATION TEST.
AB  - Neutralization tests for the virus of poliomyelitis on blood serum of urban
      mothers and their newborn infants showed that immunity was present in ten out of
      twelve (83 per cent) infants and in ten out of twelve (83 per cent) mothers, with
      a complete correspondence between mother and infant. These tests point to passive
      transmission of immunity from mother to infant. Previous tests on other children
      (1 to 5 years) indicate that immunity in infants is transitory. Previous
      observations concerning the extent of immunity in urban adults are confirmed and
      extended. The results of these tests are in accord with the age distribution of
      poliomyelitis and parallel corresponding observations in diphtheria.

PMID- 19869779
TI  - CULTIVATION OF VACCINE VIRUS.
AB  - 1. A strain of neurovaccine virus was cultivated in a medium consisting of minced
      chick embryo suspended in Tyrode's solution. 2. The virus upon cultivation
      apparently lost none of its essential characteristics. 3. The culture virus can
      be preserved and stored for long periods of time. Furthermore, the preserved
      virus can be used to initiate fresh cultures.

PMID- 19869780
TI  - THE STANDARDIZATION OF ANTIPNEUMOCOCCIC SERUM TYPES I AND II.
AB  - 1. The mouse protection test used for the standardization of anti-pneumococcic
      serum Type I and II is very unreliable. 2. The specific polysaccharide
      precipitation test can be used to establish the comparative value of a test serum
      to a standardized serum. 3. The polysaccharide used for such tests does not have
      to be of the highest purity.

PMID- 19869781
TI  - SPECIFIC PRECIPITATION AND MOUSE PROTECTION IN TYPE I ANTIPNEUMOCOCCUS SERA.
AB  - 1. A rapid and simple method is given for the approximate determination of the
      specifically precipitable protein in Type I antipneumococcus sera. 2. It is shown
      that a close parallel exists between the specifically precipitable protein and
      the number of mouse protection units in a wide variety of Type I antipneumococcus
      sera. 3. Owing to the consistent results obtained and the rapidity, simplicity,
      and economy of the method, its use is proposed instead of the mouse protection
      test as a basis for the titration of standard sera and the comparison of others
      with a standard. 4. A method is given for conveniently preparing highly purified
      specific polysaccharide of Type I pneumococcus.

PMID- 19869782
TI  - THE EFFECT OF INFLAMMATORY REACTIONS ON TISSUE IMMUNITY.
AB  - 1. Animals showing natural bacterial allergy to filtrates of B. lepisepticum
      survive infection by this organism more frequently than weak reactors. This
      increased resistance is manifested by better localization of infection. 2.
      Bacterial filtrates injected into skin 24 hours before infection exert a non
      specific protection of that area against the organism, even in susceptible
      animals. The cells of this protected area seldom undergo necrosis when infected.
      3. Severe injury of tissues either by chemicals or an antigen-antibody reaction
      produces a loss of local resistance even in immune animals. Mild injuries have
      the opposite effect. It is believed that in cases of severe injury, the affected
      areas undergo a segregation from the circulating antibodies. 4. When bacterial
      immune serum is injected with a protein antigen into the skin of a sensitized
      animal, a local alteration occurs in which substances necessary for the effective
      action of the immune serum are destroyed. 5. A protective action is restored to
      the altered immune serum by addition of complement to the lesion. 6. It is felt
      that allergy is not the chief mechanism in cellular resistance to infection,
      however data are advanced which suggest that allergy does exert local protection
      by acceleration of the immune processes and by rendering the cells locally
      refractory to further injury. 7. Chronic infection by a single strain of organism
      excites cellular reactivity to many strains of bacteria often unrelated
      biologically. Hence a non-specific mechanism for localizing infections throughout
      the body may be induced.

PMID- 19869783
TI  - HOST FACTORS IN THE PATHOGENESIS OF PNEUMOCOCCUS PNEUMONIA : I. THE REACTION OF
      THE LUNGS TO PNEUMOCOCCUS AUTOLYSATE IN SENSITIZED RABBITS.
AB  - The present study was undertaken in order to determine whether animals exhibiting
      cutaneous hypersensitiveness to pneumococcus would show an acute inflammatory
      reaction in the lungs when pneumococcus autolysate was brought into contact with
      the pulmonary tissues and, if so, whether the pulmonary reaction might be shown
      to be due to the allergic state of the animal, rather than to intrinsic
      properties of the autolysate. Twenty young rabbits were sensitized to
      pneumococcus by various procedures and their degree of hypersensitiveness
      determined at frequent intervals over varying periods of time by means of
      intracutaneous injections of pneumococcus autolysate standardized on the basis of
      nitrogen content and so treated as to be devoid of the known toxic principles.
      Twenty-four hours after the last skin test each rabbit was injected
      intratracheally with the same pneumococcus autolysate. Seven non-sensitive
      controls were similarly injected intratracheally. Twenty-four hours after
      intratracheal injection the rabbits were killed. The lungs were removed, a
      portion was cultured, and the rest was examined histologically. Of the twenty
      sensitized rabbits, three that showed no cutaneous sensitivity and three that
      were only slightly skin-sensitive at the time of intratracheal injection
      exhibited no detectable pulmonary reaction to the autolysate; eleven of fourteen
      that showed moderate to extreme cutaneous hypersensitiveness were found to have
      an acute exudative inflammation of the lungs. The exudate consisted largely of
      polymorphonuclear leukocytes and serum. It varied in extent from a slight focal
      exudate lining the bronchioles and adjacent alveoli to a very marked diffuse
      involvement of considerable portions of the lung. In all but one of the eleven
      the cultures of the lungs were sterile. The single animal showing a positive
      culture (B. lepisepticum) has been excluded. None of the seven non-sensitive
      controls showed any pulmonary reaction to the autolysate. From these results it
      may be concluded that there is in rabbits a fairly close parallelism between
      cutaneous and pulmonary hypersensitiveness to pneumococcus autolysate and that
      the inflammatory response of the pulmonary tissue resulting from contact with the
      autolysate depends upon the allergic state of the animal rather than upon
      inherently injurious substances in the autolysate. The observations are in
      harmony with the theory that allergy may play a part in the pathogenesis of
      pneumococcus pneumonia in man.

PMID- 19869784
TI  - STUDIES ON A-AVITAMINOSIS IN CHICKENS : I. LESIONS OF THE RESPIRATORY TRACT AND
      THEIR RELATION TO SOME INFECTIOUS DISEASES.
AB  - 1. The principal tissue changes in the respiratory tract of chickens caused by a
      vitamin A deficiency in the food are, first, an atrophy and degeneration of the
      lining mucous membrane epithelium as well as of the epithelium of the mucous
      membrane glands. This process is followed or accompanied by a replacement or
      substitution of the degenerating original epithelium of these parts by a squamous
      stratified keratinizing epithelium. This newly formed epithelium develops from
      the primitive columnar epithelium and divides and grows very rapidly. The process
      appears to be one of substitution rather than a metaplasia, and resembles the
      normal keratinization of the skin or even more closely the incomplete
      keratinization of the mucous membranes (e.g., the esophagus or certain parts of
      the tongue of chickens). In this connection findings have been described which
      not only afford an interesting insight into the complicated mechanism of
      keratinization, but also show probable relations between keratinization and the
      development of Guarnieri's inclusion bodies. Balloon and reticular degeneration
      of the upper layers of the new stratified epithelium has been frequently
      observed. All parts of the respiratory tract are about equally involved in the
      process; and the olfactory region as well, so that the sense of smell may be
      lost. The lesions, which first take place on the surface epithelium and then in
      the glands, show only minor differences. 2. The protective mechanism inherent in
      the mucous membranes of the entire respiratory tract is seriously damaged or even
      entirely destroyed by the degeneration of the ciliated cells at the surface and
      the lack of secretion with bactericidal. properties. Secondary infections are
      frequently found, and nasal discharge and various kinds of inflammatory processes
      are common, including purulent ones, especially in the upper respiratory tract,
      communicating sinuses, eyes and trachea. The development of the characteristic
      histological process is not dependent upon the presence of these infections,
      since it also takes place in the absence of infection. 3. The specific
      histological lesions make it possible to differentiate between A-avitaminosis and
      some infectious diseases of the respiratory tract. These studies we hope will
      serve as a basis for further investigations on the relationship between A
      avitaminosis and infection in general.

PMID- 19869785
TI  - STUDIES ON A-AVITAMINOSIS IN CHICKENS : II. LESIONS OF THE UPPER ALIMENTARY TRACT
      AND THEIR RELATION TO SOME INFECTIOUS DISEASES.
AB  - When fowls are placed on a diet lacking in vitamin A lesions appear in the upper
      alimentary tract which are confined largely to the mucous glands and their ducts.
      Histologically it is shown that the original epithelium becomes replaced by a
      stratified squamous keratinizing epithelium and that secondary infections are
      relatively common. The ducts of the glands may be blocked leading to distention
      with secretions and necrotic materials. These lesions macroscopically resemble
      very closely certain stages of fowl-pox and the two conditions can be separated
      only by histological examination. It is pointed out that these lesions produced
      by a lack of vitamin A may enable bacteria and other viruses to enter the body.

PMID- 19869786
TI  - THE DISTRIBUTION OF FRIEDLANDER'S BACILLI OF DIFFERENT TYPES.
AB  - In a study of the distribution of the specific types of Friedlander's bacillus,
      it is shown that: (1) Of 80 strains 52 per cent belong to Type A, 15 per cent to
      Type B, 9 per cent to Type C, and 24 per cent to Group X. (2) Type A contains for
      the most part strains derived from diseases of man and more than 70 per cent are
      associated with pneumonia in man. (3) Type B includes the greatest number of
      strains from animal sources, while the heterogeneous strains comprising Group X
      come from the greatest variety of diseases. It was demonstrated that in a patient
      suffering with pneumonia due to Friedlander's bacillus (Type A), a specific
      precipitin reaction of the urine occurred in the corresponding (Type A) immune
      serum. A study of the sugar fermentation reactions of Friedlander's bacillus
      shows that (1) there is no correlation between serological type and fermentative
      activity; (2) the fermentation reactions are variable and therefore not reliable
      for distinguishing Friedlander's bacillus from closely allied organisms; (3) the
      strains of Group X show the greatest variation in fermentation, and (4) of 15
      strains unable to ferment lactose, 13 belong to Type A.

PMID- 19869787
TI  - STUDIES OF DISEASES OF THE LYMPHOID AND MYELOID TISSUES. I : THE CHEMICAL
      METABOLISM OF NORMAL AND PATHOLOGICAL LYMPH NODES.
AB  - From a study of the metabolism of 71 lymph nodes and tumors one may conclude: 1.
      The nature of a tumor can not be predicted from the metabolism because too much
      overlapping of metabolic rates exists between the pathological groups. 2. There
      is no evidence metabolically one way or another as to whether malignant
      lymphomata of any type should be classed as neoplastic or as infectious
      processes. 3. The degree of cell differentiation can in most cases be foretold by
      the percentage difference between the aerobic and the anaerobic glycolysis. The
      greater the differentiation the greater the percentage difference. Sarcomata in
      general constitute an exception to this rule. 4. The degree of malignancy in
      carcinoma, but not in other tumors, can, with certain exceptions, be predicted
      from the height of the value U. 5. Human sarcomata appear to have a metabolism
      far more closely comparable to that of benign tumors than to that of carcinomata.
      They do not behave as malignant tumors under the Warburg classification. Their
      energy requirements are not of the same order as those of carcinoma. 6. One can
      not from the value U or from the glycolytic rates predict whether or not a tissue
      should be classed as neoplastic. 7. Warburg's findings for carcinomata are
      confirmed and amplified.

PMID- 19869788
TI  - SEROLOGICAL REACTIONS IN PNEUMONIA WITH A NON-PROTEIN SOMATIC FRACTION OF
      PNEUMOCOCCUS.
AB  - 1. Sera from individuals acutely ill with lobar pneumonia possess the capacity to
      precipitate in high titre a non-protein somatic fraction derived from pneumococci
      (Fraction C). Following crisis the reaction is no longer demonstrable. 2. Sera
      obtained from cases of pneumococcus pneumonia during illness and convalescence
      have been tested for antibodies specifically reactive with three chemically
      distinct constituents of Pneumococcus. The results, when correlated with the
      course of disease, demonstrate differences in the occurrence of each
      qualitatively distinct antibody. 3. The precipitation of pneumococcus Fraction C
      is not limited to the sera of individuals ill with pneumococcus infection. But in
      the few other cases available for comparative tests, definite reactions have been
      obtained only in streptococcus and staphylococcus infections and in acute
      rheumatic fever.

PMID- 19869789
TI  - CUTANEOUS REACTIONS IN PNEUMONIA. THE DEVELOPMENT OF ANTIBODIES FOLLOWING THE
      INTRADERMAL INJECTION OF TYPE-SPECIFIC POLYSACCHARIDE.
AB  - The majority of patients convalescent from pneumonia due to Types I, II and III
      Pneumococcus develop at the time of recovery circulating antibodies for the
      homologous type of organisms. At the same time an immediate wheal and erythema
      reaction followed the intradermal injection of the homologous type-specific
      polysaccharide in 100 per cent of Type I patients, 58.8 per cent of Type II
      patients, and 44 per cent of Type III patients. In a group of 18 patients
      repeatedly tested with the type-specific polysaccharides, 10 developed in the
      second or third week of convalescence circulating antibodies for one or more
      heterologous types. In none of 21 control patients was this phenomenon observed.
      It is suggested that the development of circulating antibodies for heterologous
      types of Pneumococcus was associated with the previous intradermal injections of
      the type-specific polysaccharides.

PMID- 19869790
TI  - IMMUNOLOGICAL STUDIES IN RELATION TO THE SUPRARENAL GLAND : VI a. TRYPANOSOMA
      LEWISI INFECTION IN NORMAL ALBINO RATS VI b. TRYPANOSOMA LEWISI INFECTION IN
      SUPRARENALECTOMIZED ADULT ALBINO RATS.
AB  - Bilateral suprarenalectomy in rats lowers the resistance to a subsequent
      infection with T. lewisi. Almost 70 per cent of these rats die within an average
      period of 5.8 days after infection. The multiplication of the parasites in the
      circulating stream is not more considerable than in rats previously normal nor is
      the duration of the disease in the surviving rats any longer than in the normal
      group. Bilateral suprarenalectomy does not prevent the formation of immune
      substances to the parasites but appears to lower the natural resistance of the
      rat to the toxic effects of the protozoan infection. The acquired immunity to T.
      lewisi of normal rats as a result of infection is not broken down by subsequent
      suprarenalectomy. Unilateral nephrectomy does not affect the course of a
      subsequent infection with T. lewisi.

PMID- 19869791
TI  - FURTHER STUDIES ON T. LEWISI INFECTION IN ALBINO RATS : I. THE EFFECT OF
      SPLENECTOMY ON T. LEWISI INFECTION IN ALBINO RATS AND THE PROTECTIVE ACTION OF
      SPLENIC AUTOTRANSPLANTS II. THE EFFECT OF THYMECTOMY AND BILATERAL GONADECTOMY ON
      T. LEWISI INFECTION IN ALBINO RATS.
AB  - T. lewisi infection in normal adult 3 month old albino rats raised from a single
      stock and maintained under identical conditions was studied. Daily quantitative
      estimates of the trypanosomes in the circulating blood were made and the course
      of the infection was studied. Bilateral suprarenalectomy in rats lowers the
      resistance to a subsequent infection with T. lewisi. About 70 per cent of these
      rats die in an average period of 5.8 days after injection. The multiplication of
      the parasites, in the circulating stream, however, is not more considerable in
      the suprarenalectomized than in the previously normal rats, nor is the duration
      of the disease in the surviving rats any longer than in the normal group. The
      removal of the suprarenal glands does not alter the immune reaction to the
      parasite, but lowers the natural resistance of the animal to the toxic effects of
      the protozoan infection. Bilateral suprarenalectomy does not lessen the immunity
      of rats recovered from T. lewisi infection to subsequent infection. Unilateral
      nephrectomy does not influence the course of a subsequent infection with T.
      lewisi infection. The mortality of splenectomized rats from Bartonella muris
      anemia increases from 30 to 100 per cent following the injection of T. lewisi at
      the height of the anemia 7 days after splenectomy. T. lewisi infection 48 days
      after splenectomy that is to say at a time when the Bartonella anemia is no
      longer present produces a more severe infection than in normal rats. The number
      of trypanosomes at the height of infection averages 3 times the ordinary and the
      infection endures twice as long. Both the immune substance that inhibits the
      reproduction of the parasite and the lytic factor are markedly depressed. Splenic
      autotransplantation performed 4 weeks prior to splenectomy raises the resistance
      of rats to a subsequent T. lewisi infection. Thymectomy in 6 week old rats
      diminishes the severity of a subsequent trypanosome infection and shortens its
      course. Both the formation of the immune substance which inhibits reproduction of
      the trypanosomes and formation of trypanolytic antibodies are stimulated by this
      procedure. In the adult rat thymectomy shortens the course of the infection but
      the severity is only slightly diminished. Bilateral gonadectomy in the adult
      increases the severity of the infection. The number of trypanosomes at the height
      of the infection is almost three times the normal. However, the duration of the
      infection is the same as in the normal rats. The reproduction-inhibiting factor
      is depressed by bilateral gonadectomy but not the trypanocidal factor. Unilateral
      gonadectomy does not influence the infection.

PMID- 19869792
TI  - BACTERIUM GRANULOSIS IN RELATION TO TRACHOMA: ITS RECOVERY FROM EXPERIMENTALLY
      INFECTED MONKEYS AND FROM HUMAN TRACHOMA.
AB  - One of the strains of Bacterium granulosis isolated by Noguchi in 1926 has been
      maintained in culture and in monkeys and continues to be capable, after 3 years,
      of inducing a chronic granular conjunctivitis in monkeys. Cultures of this strain
      have been recovered from the monkey lesions as late as 3 years after inoculation
      and have been shown to reproduce the granular disease in monkeys. Six additional
      strains of Bacterium granulosis have been isolated from cases of trachoma
      occurring in the Indian schools of Arizona. The cultures thus obtained are
      identical morphologically and culturally with those isolated by Noguchi and have
      induced the same chronic granular conjunctivitis in monkeys. Advanced untreated
      cases are more favorable for cultural study than treated cases. Cultures of
      Bacterium granulosis kept on semisolid medium containing 10 per cent rabbit serum
      ("leptospira medium") remain viable for many months at room temperature, and
      sealed ampoules of such cultures have been found to retain their pathogenicity
      for the monkey conjunctiva for at least 69 days at room temperature and at least
      284 days at 4 degrees to 6 degrees C. Several additional cultural and biological
      characteristics of Bacterium granulosis have been described. Of outstanding
      importance is the fact that cocaine, in contradistinction to novocain, has a
      bactericidal effect on the organism. This fact, in view of the common use of
      cocaine for anesthesia, may explain the negative results of cultivation
      experiments reported by some workers.

PMID- 19869793
TI  - THE TRANSMISSION OF PERIODIC OPHTHALMIA OF HORSES BY MEANS OF A FILTERABLE AGENT.
AB  - A filterable agent has been obtained from the humors and tissues of the eyes of
      horses suffering from active periodic ophthalmia. The intra-vitreous injection of
      this filtrate produced in normal horses the same clinical and pathological
      picture observed in the natural disease. This filtrate injected into rabbits
      produced a different clinical picture, but the essential pathological lesions
      closely resembled those found in horses. After passage of the filterable agent
      through six generations of rabbits, it again produced the clinical and
      pathological picture of the natural disease when injected into the eyes of normal
      horses. It appears, in this epidemic at least, that this filterable agent was the
      specific etiological factor of the periodic ophthalmia.

PMID- 19869794
TI  - STUDIES ON TYPHUS FEVER : II. STUDIES ON THE ETIOLOGY OF MEXICAN TYPHUS FEVER.
AB  - We have adduced strong evidence in favor of identifying the virus of Mexican
      typhus fever with the Rickettsiae, or Mooser bodies, observed in the tunica
      lesions of Mexican typhus guinea pigs. Were it not for the possible presence of a
      few remaining cell fragments in the washings we would consider this evidence
      crucial proof.

PMID- 19869795
TI  - STUDIES ON TYPHUS FEVER : III. STUDIES OF LICE AND BEDBUGS (CIMEX LECTULARIUS)
      WITH MEXICAN TYPHUS FEVER VIRUS.
AB  - Our experiments have shown that the Mooser bodies or Rickettsiae derived from
      guinea pigs with Mexican typhus fever can survive in bedbugs after intra-coelomic
      injection for 10 days, remaining capable of infection. We have also succeeded in
      similarly infecting bedbugs by allowing them to feed on benzolized rats in whose
      blood Rickettsiae had been shown to be present. Injection of the organs of such
      bedbugs 5 days after the last, 9 days after the first infectious feeding into
      guinea pigs produced typical Mexican typhus fever. Some of the guinea pigs
      infected with such bedbug organs and passing through a typical typhus proved to
      be immune to subsequent inoculation with the European disease. Attempts to infect
      normal guinea pigs by allowing infected bedbugs to feed on them or by rubbing the
      feces into the uninjured skin have, so far, been unsuccessful. We have not,
      therefore, completed the cycle proving that bedbugs can transmit the disease, but
      we have shown that this is a possibility when dealing with man, obviously more
      susceptible to the disease than any of our experimental animals. The ease with
      which the Rickettsiae seem to survive in the bedbugs suggests the desirability of
      investigating other common insects for a similar capacity of harboring the typhus
      Rickettsiae-experiments which we have not yet had the time to carry out.

PMID- 19869796
TI  - EXPERIMENTAL FIBROUS OSTEODYSTROPHY (OSTITIS FIBROSA) IN HYPERPARATHYROID DOGS.
AB  - These experiments have shown that parathyroid extract (parathormone Collip) can
      be injected into puppies in increasing amounts for long periods without fatal
      results. Thus time is allowed for bone changes to develop. Long continued
      injection leads to progressive decalcification and resorption of the existing
      bone, to fibrous replacement of the marrow, and to the production of the other
      features characteristic of ostitis fibrosa. Deformities eventually appear. It is
      safe to assume that the bone changes produced by hyperparathyroidization have the
      same pathogenesis as those observed in clinical cases believed to be instances of
      hyperparathyroidism-that is, cases with a negative mineral balance and
      decalcification of the skeleton.

PMID- 19869797
TI  - A COMPARISON OF THE CHEMICAL ALTERATIONS IN THE BLOOD OF RATS INFECTED WITH
      PATHOGENIC AND NON-PATHOGENIC TRYPANOSOMES.
AB  - Blood samples from rats infected with Trypanosoma lewisi give normal values for
      lipoid phosphorus, lecithin, CO(2) combining capacity, and liver glycogen. When
      these results are compared with the results of similar experiments with T.
      equiperdum infections, on the basis of the concentration of trypanosomes in the
      blood, it is found that the pathogenicity of the latter organism does not depend
      upon its numbers as affecting the blood, but that it must be in some other way
      injurious to the host. Whether the injury is due to a true toxin, an endotoxin,
      or mechanical interference is not yet known.

PMID- 19869798
TI  - STUDIES IN THE COMMON COLD : IV. EXPERIMENTAL TRANSMISSION OF THE COMMON COLD TO
      ANTHROPOID APES AND HUMAN BEINGS BY MEANS OF A FILTRABLE AGENT.
AB  - 1. Chimpanzees are highly suitable animals for the experimental study of human
      upper respiratory infections. 2. Human colds have been successfully transmitted
      to apes and human volunteers in 44 per cent of instances tried by means of
      filtered nasal washings obtained from colds. 3. Certain types of infectious colds
      are caused by a filtrable agent.

PMID- 19869799
TI  - STUDIES IN THE SEROLOGY OF SYPHILIS : I. THE MECHANISM OF THE FLOCCULATION
      REACTIONS.
AB  - A. The lipoid antigen used in the serum diagnosis of syphilis, when colloidally
      dispersed in water, forms a relatively stable amphoteric suspension with
      predominantly hydrophilic properties. Although the colloidal particles flocculate
      at their isoelectric point (pH 1.9), in more alkaline reaction the negative
      surface potential prevents their cohesion and must be depressed to 1 to 5
      millivolts before visible flocculation is obtained, indicating a very slight
      affinity between the colloidal particles. The amount of electrolyte necessary to
      depress this surface charge below its critical value decreases somewhat with
      increasing concentration of the sol, but is uniformly large: in a suspension
      containing 0.04 per cent lipoid, 1 M univalent and 1/40 M bivalent cation are the
      coagulation values. B. In normal serum, hydrophilic protein is adsorbed, forming
      a protective film around the individual lipoid particles, with a corresponding
      change in the cataphoretic potential and the isoelectric point towards those of
      serum protein, the degree of shift depending upon the extent of the adsorbed
      film. The critical potential, however, is not affected, and the lipoid remains as
      stable away from its isoelectric point as in the absence of serum. The water
      soluble film of unchanged protein is readily removed by washing, and does not
      prevent the subsequent combination of the underlying lipoid with the specific
      component of syphilitic serum. C. When the lipoid antigen is added to syphilitic
      serum, in addition to this loose adsorption of normal protein it combines more or
      less irreversibly with a specifically altered fraction of the serum globulin
      (reagin), demonstrable in the washed precipitate both chemically and by
      sensitization experiments. Like adsorbed normal serum, it depresses the surface
      potential and causes a shift in the isoelectric point; but there the similarity
      ends. The reagin-globulin is rendered water-insoluble by its firm combination
      with the lipoid, exactly as any antibody is denatured upon combination with its
      specific antigen (bacteria, red cells, or dissolved protein). The hydrophobic
      films of reagin have five times as great an affinity for each other as the
      original lipoid surfaces; accordingly, the critical potential is raised from its
      original value of 1 to 5 millivolts to 10 to 15 millivolts, that of particles of
      denatured globulin or of any antigen-antibody complex, and relatively small
      quantities of electrolytes (at serum pH, cations) suffice to depress the
      stabilizing potential below this critical level, with resultant aggregation and
      flocculation. In brief, a specific globulin combines with the colloidal particles
      of the antigen, conferring upon them the unstable properties of a suspension of
      denatured protein. Like the antibody film on bacteria, or red cells, and unlike
      normal adsorbed protein, the reagin globulin on the lipoid particle can adsorb
      ("fix") complement. When this protein film is destroyed by heat-coagulation, the
      complement-fixing property is lost; concomitantly, the specific groups of the
      lipoid having been freed from the closely adherent reagin, the antigen becomes
      again active, able to react with more syphilitic serum. These changes in the
      properties of reagin globulin upon its combination with the lipoid antigen
      (denaturation) are in every sense analogous to those effected in any antibody by
      its specific antigen, and are probably due to the same, as yet unknown, factors.
      It has been suggested for bacterial and red cell "agglutinins" and protein
      "precipitins," that the groups of the antibody determining its specificity are
      also those which endow it with its hydrophilic properties; when these combine
      with antigen, residual free hydrophobic groups determine the surface properties
      of the complex. The same tentative hypothesis may be offered for the denaturation
      of reagin globulin by the lipoid antigen. The complete analogy between the
      flocculation reactions for syphilis and the so-called specific reactions
      (bacterial and red cell agglutination; protein precipitation) suggests that like
      agglutinins, precipitins, etc., reagin globulin represents an antibody response
      to products of infection.

PMID- 19869800
TI  - STUDIES IN THE SEROLOGY OF SYPHILIS : II. THE PHYSICAL BASIS OF THE WASSERMANN
      REACTION.
AB  - The substance in syphilitic serum which is responsible for the Wassermann
      reaction, like that which determines the diagnostic flocculation tests, is
      associated with the globulin fraction of serum. Every positive Wassermann is
      accompanied by microscopic (or submicroscopic) aggregation, which is not an
      essential feature of the reaction; conversely, after every positive flocculation
      test, the washed precipitate will fix complement. An excess of antigen removes
      both flocculating and complement-fixing substances completely (>95 per cent).
      Heating the lipoid-reagin precipitate to 100 degrees for 1 minute destroys the
      sensitizing film of reagin globulin; the avidity for complement disappears
      simultaneously. Both the flocculating and complement-fixing properties of
      syphilitic serum are therefore determined by the same substance, a specifically
      altered fraction of the serum globulin, reagin. The Wassermann reaction is thus
      entirely analogous to complement fixation by any antigen-antibody complex. The
      same film of denatured serum globulin which sensitizes the antigen particles,
      whether red cells, bacteria, protein, or colloidal lipoid particles, to discharge
      and aggregation by electrolytes, also endows them with an avidity for complement.
      The pathogenesis of reagin will be discussed in a forthcoming paper.

PMID- 19869801
TI  - STUDIES IN THE SEROLOGY OF SYPHILIS : III. EXPLANATION OF THE FORTIFYING EFFECT
      OF CHOLESTERIN UPON THE ANTIGEN AS USED IN THE WASSERMANN AND FLOCCULATION TESTS.
AB  - When cholesterinized antigen is dropped into an excess of water, the rapid
      flocculation of cholesterin crystals is prevented by the fact that, as tiny
      aggregates form, they adsorb a protective surface of hydrophilic lecithin (i.e.,
      antigen) which endows the particles with its own stable surface properties and
      thus prevents further aggregation. The colloidally dispersed antigen-cholesterin
      particles have approximately the same isoelectric point (pH 1.9), critical
      potential (1 to 5 millivolts) and coagulation value (0.75 M NaCl) as pure antigen
      particles of the same concentration, while the corresponding values for
      cholesterin are pH 2.1 to 3.4 (probably due to an associated impurity), >100
      millivolts, and <0.001 N NaCl, respectively. Presumably, this adsorption of
      antigen by the cholesterin nucleus is determined by the fact that the former has
      a lower surface tension against water. At any rate, many surface active
      substances (serum; alcoholic extract of milk, egg or any animal tissue; Na
      oleate; Na-glycocholeate; Na-taurocholate) cause a similar stable dispersion of
      cholesterin; and conversely, many otherwise water-insoluble substances of the
      most diverse chemical structure can be made to form a stable colloidal suspension
      by adding antigen to their alcoholic solutions before dropping into water. The
      colloidal suspension formed by antigen alone is very finely dispersed: only a few
      of the particles exceed the limits of dark field visibility. Cholesterin causes a
      marked increase in the number of these particles, out of all proportion to its
      mass; thus, one part of cholesterin to five of antigen causes a ten-fold increase
      in such visible particles, at the expense of the submicroscopic micellae formed
      by antigen alone. At the same time, the suspension becomes much more turbid. The
      particles remain discrete until the cholesterin: antigen ratio exceeds 1:1, when
      slight microscopic aggregation is observed; microscopic flocculation is seen only
      when this ratio exceeds 5:1, when there is not sufficient antigen to act as an
      efficient protective colloid. Cholesterin therefore causes a coarsened dispersion
      of antigen by forming a relatively large nucleus upon which antigen is adsorbed.
      As shown in the text, the larger the antigen particle the greater is its avidity
      for reagin per unit surface or mass. Thus, the coarse sol formed by dropping
      water-into-antigen is about twice as efficient as a finely dispersed antigen-into
      water sol of the same concentration. The coarsened dispersion caused by
      cholesterin completely explains the greater sensitivity of the cholesterinized
      antigen in complement fixation. The same factor obtains in the flocculation
      reactions. In addition, the coarsened dispersion acts as a preliminary quasi
      aggregation, facilitating by just so much the subsequent formation of visible
      clumps (or sedimenting aggregates) upon the addition of syphilitic serum;
      moreover, there is less surface in a coarse sol, with more reagin per unit
      surface, and correspondingly more efficient flocculation. The foregoing would be
      of purely academic interest were it not for the following considerations. From
      several points of view cholesterin is unsatisfactory as a sensitizer for antigen.
      Its solubility in alcohol is small. Even the 0.6 per cent concentration used in
      the Kahn test is difficult to keep in solution. Yet, as our experiments show, its
      sensitizing action increases indefinitely with its concentration. If it were
      sufficiently soluble, even 3 per cent could be used to advantage, increasing the
      sensitivity of 1(1/2) per cent antigen for complement fixation some 200 to 400
      per cent, instead of about 50 per cent, as does 0.2 per cent cholesterin. Since,
      as we have shown, the sensitizing action of cholesterin upon antigen is due
      solely to the coarse dispersion it causes, and since it is quite inert during the
      actual combination of the lipoid particles with reagin, it can be replaced by any
      substance with similar physical properties. The problem in hand was therefore to
      find a water-insoluble substance, very soluble in alcohol, with so high an
      interfacial tension against water that, as in the case of cholesterin,
      microscopic particles would adsorb antigen when the alcoholic solution of the two
      is dropped into water. Given such a substance, it would be possible to obtain a
      more sensitive antigen for both complement fixation and flocculation, but
      particularly for the former. These theoretical expectations have been realized in
      a group of substances shortly to be reported: they make possible an antigen which
      is from 2 to 10 times as efficient in the Wassermann test as any now available.

PMID- 19869802
TI  - THE KILLING OF COLON BACILLI BY X-RAYS OF DIFFERENT WAVE LENGTHS.
AB  - X-ray beams of wave lengths lying in the range between 4 A and 0.5 A all kill B.
      coli in a semilogarithmically linear fashion. Interpreted in terms of the known
      quantized absorption of X-rays, this means that one absorption of any of these
      radiations is sufficient to kill. Though death results from a single absorption,
      only about one hit in four with Ag K and one in sixty with Ag L radiation is
      deadly. The course of curves constructed from these experimental results suggests
      that the portion of this bacterium which is essential to its continued life has a
      total of approximately 0.01 of the cell volume. For copper and harder radiations
      the biological action of the rays is proportional to their measured air
      ionization. The same biological change with the softer chromium K. and silver L X
      rays seems to require a somewhat more intensely ionizing beam.

PMID- 19869803
TI  - THE EFFECT OF BACTERIAL VARIATION UPON THE FACTORS NECESSARY FOR THE PHENOMENON
      OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES.
AB  - In this paper there is reported the effect of bacterial variation upon the
      reacting factors of the phenomenon of local skin reactivity to bacterial culture
      filtrates. By means of the method described in the text the following results
      were obtained: Various stock strains of B. typhosus were found to produce
      reacting factors which differed in their neutralizability by anti-stock immune
      sera. The reacting factors of low neutralizability also possessed low
      antigenicity. The passage of strains through mice brought about in one instance a
      lowering of neutralizability of reacting factors and in another instance had no
      effect. It was possible to increase the antigenicity of the reacting factors by
      passage of the strain through mice. Transformation of "stock" strain into "rough"
      brought about the formation of reacting factors of new specificity. The "rough"
      reacting factors were neutralized by homologous sera and also differed in their
      neutralizability. Reacting factors of various degrees of neutralizability were
      produced by stock strains which did not display any difference in colony
      appearance (with one exception). The "rough" reacting factors appeared in strains
      of typical "rough" colony morphology. However, "rough" strains of the same degree
      of roughness morphologically differed in the neutralizability of their reacting
      factors. The changes in neutralizability elicited by passage through mice had no
      influence on colony morphology. There seemed to be a parallelism between the
      degree of agglutinability of stock strains by anti-stock sera and the degree of
      neutralizability of reacting factors of the same strain. It was possible to
      obtain a partial loss of neutralizability by passage through mice with and
      without change in agglutinability. The agglutination titer of anti-rough serum
      was not an indication of its anti-rough neutralizing properties. The degree of
      neutralizability of "rough" reacting factors paralleled the specific serum
      agglutinability of the strains producing them. Abundant precipitation occurred in
      mixtures of toxic filtrates and immune serum in spite of low neutralization. The
      filtrates of rough cultures non-neutralizable by anti-stock sera failed to
      precipitate with the latter. The appearance of neutralizing anti-rough antibodies
      was coincident with the development of anti-rough precipitates. The rough strains
      possessed a lower virulence than the stock strains from which they were derived.
      However, there was no difference in the virulence of "rough" strains, the
      reacting factors of which differed in their neutralizability. The filtrates
      containing "rough" reacting factors were seemingly as lethal to mice and rabbits
      as were filtrates of stock cultures of B. typhosus. The possible relation of
      these findings to the immunological understanding of the course of infectious
      diseases and to serum therapy is discussed.

PMID- 19869804
TI  - THE ANTIRACHITIC ACTION OF COD LIVER OIL AND IRRADIATED ERGOSTEROL IN
      PARATHYROIDECTOMIZED AND THYMECTOMIZED RATS.
AB  - Cod liver oil and Viosterol in therapeutic doses are antirachitic in the absence
      of the parathyroid gland, or of the thymus, or of both.

PMID- 19869805
TI  - SPECIFIC POLYSACCHARIDES FROM FUNGI.
AB  - From each of five yeast-like fungi and a trichophyton there has been prepared a
      fraction which appears to be essentially a polysaccharide. Tested by direct
      precipitation against the corresponding antisera the polysaccharides from the
      yeast-like fungi exhibit only partial specificity. Cross-precipitin reactions are
      frequent. By absorption of precipitin on the intact mycotic bodies, however, a
      relatively high degree of specific precipitability can be demonstrated for the
      polysaccharides.

PMID- 19869806
TI  - STUDIES ON MOUSE LEUKEMIA : III. A COMPARISON OF FOUR LINES OF LEUKEMIA
      TRANSMITTED BY INOCULATION.
AB  - Several lines of lymphatic leukemia in mice, experimentally transmitted by
      inoculation into hosts of a closely inbred strain, have been established and
      carried on simultaneously. Among the inoculated mice there were found different
      types of response, according to the line of leukemia inoculated. The differences
      consisted mainly in the extent or distribution of lesions. Although the same line
      did not always show the same distribution of lesions, there was a distinct
      tendency for the cases in a line to present the same characteristics on
      successive transfers over a considerable period. A comparison of the frequency of
      the occurrence of certain lesions in four lines of transmission shows that: 1.
      Increases in the total leucocyte counts were less common and less marked in Lines
      A and E than in Lines H and I. In the lines first mentioned, normal counts were
      relatively frequent. In Line H normal counts were uncommon, and in Line I were
      not observed. The highest counts were found in Line I. 2. Peritoneal effusion was
      characteristic of Line A for 43 transfers. It was found in Line E, but for a
      considerably shorter period and in a smaller proportion of cases; it was rare in
      Lines H and I. 3. Pleural effusion was frequently found in Lines A and E but
      rarely in Lines H and I. 4. Infiltration in the liver occurred to a marked degree
      in all the mice of Lines H and I, but in fewer mice and to a variable degree in
      Lines A and E. 5. Infiltration in the kidney in Line I was present in 90 per cent
      of the mice, and was of marked grade. In line H it was present in 67 per cent of
      the mice (24 per cent of marked grade) but in Lines A and E it was rare. 6. A
      considerable amount of variability in results occurred in Lines A and E, whereas
      Lines H and I remained remarkably constant. The lesions characteristic of a line
      were not necessarily those present in the spontaneous case from which the first
      transfer of the line was made. As the mice used for inoculation were genetically
      uniform, the differences between the lines are not due to genetic differences in
      the hosts, but to differences in the materials inoculated.

PMID- 19869807
TI  - OBSERVATIONS ON NORMAL SYNOVIAL FLUID OF CATTLE : I. THE CELLULAR CONSTITUENTS
      AND NITROGEN CONTENT.
AB  - 1. The astragalotibial (hock) joints of normal young beef cattle contain large
      and uniform quantities of synovial fluid which is easily accessible for study. 2.
      Nucleated cells found in such synovial fluid are similar in numbers and types to
      those described previously in normal rabbits' synovia. 3. The fact that 90 to 95
      per cent of all nucleated cells present are actively phagocytic implies that the
      function of these cells is the removal of the products of wear and tear from the
      articular cartilages and synovial membranes. 4. Red blood corpuscles seem to be
      present in numbers directly proportional to the trauma to which the synovial
      membrane is subjected. 5. The astragalotibial joints of young beef cattle contain
      from 3 to 5 times more fluid than do the corresponding joints of stable cattle.
      More debris and unidentified solid material is found in the latter group of
      animals. 6. The total nitrogen content of this synovial fluid was found to be 169
      mg. per 100 cc. The approximate total protein content was calculated to be 680
      mg. or 0.68 per cent per 100 cc. 7. No correlation between the total protein
      level and the total cell counts of isolated specimens of synovial fluid is
      possible from these data. 8. Further studies of synovial fluid and of its
      chemical similarity to blood serum of the same animals are in progress. 9.
      Articular cartilage defects occurring in the articular cartilages of the
      carpometacarpal joints are described. (A more detailed study of these articular
      cartilage lesions, the age at which they appear, possible causative factors,
      etc., is now being made.).

PMID- 19869808
TI  - THE PRODUCTION OF INFECTION WITH PNEUMOCOCCI IN RABBITS BY INTRADERMAL
      INOCULATION OF TYPE III PNEUMOCOCCI, THE TREATMENT WITH SPECIFIC ANTISERUM, AND A
      COMPARISON WITH TYPE I INFECTIONS.
AB  - Intradermal lesions and subsequent bacteremia were produced in rabbits by the
      intradermal inoculation of Type III strains freshly isolated from pneumonia
      cases. Slight intradermal lesions were produced but no bacteremia was found in
      rabbits inoculated with an old stock Type III strain. The intradermal lesions and
      the bacteremia produced by the inoculation of Type III cultures in rabbits were
      usually less severe than those produced by the inoculation of Type I culture. The
      bacteremia in rabbits was checked and the rabbits protected by suitable amounts
      of Type III concentrated antiserum given intravenously 24 hours after the
      infecting dose. The amount of Type III antiserum necessary to protect rabbits
      inoculated intradermally with virulent Type III cultures was not appreciably
      greater than the amount of Type I antiserum required to protect against Type I.

PMID- 19869809
TI  - FURTHER EXPERIMENTS IN TYPHUS FEVER : IV. INFECTION WITH WASHED MEXICAN
      RICKETTSIAE AND IMMUNITY TO EUROPEAN TYPHUS.
AB  - PRECISE INTERPRETATION OF OUR EXPERIMENTS SEEMS TO IMPOSE THE FOLLOWING
      CONCLUSIONS: Guinea pigs inoculated with washed Rickettsiae from Mexican typhus
      fever develop a disease identical with that resulting from inoculations with
      whole tunica scrapings, blood or other virulent material, and become thereby
      immunized to European typhus fever. The etiological agent of Mexican typhus fever
      is the Rickettsia body of the type described by Mooser (5) in the tunica
      vaginalis of infected guinea pigs; and it is likely that the etiological agent of
      European typhus fever is an organism similar to this, but not identical with it
      in some of its minor biological characteristics.

PMID- 19869810
TI  - THE REACTION OF THE ALBINO RAT TO THE INTRA-AURAL ADMINISTRATION OF CERTAIN
      BACTERIA ASSOCIATED WITH MIDDLE EAR DISEASE.
AB  - The infective capacity of three bacteria commonly encountered during a study of
      natural middle ear disease in a rat colony has been determined by direct intra
      aural injection in young rats. One week after the introduction of B. actinoides
      75 per cent of the rats showed a purulent exudate in the injected middle ear
      cavity and 65 per cent yielded pure cultures of the organism. With hemolytic and
      non-hemolytic streptococci 75 per cent showed a serous or mucoid exudate and 12
      per cent yielded the organism in culture. With a diphtheroid 18 per cent showed a
      gross reaction in the middle ear which was sterile in every case. The
      experimental findings are discussed in relation to the etiology of middle ear
      disease.

PMID- 19869811
TI  - STREPTOCOCCI IN INFECTIOUS (ATROPHIC) ARTHRITIS AND RHEUMATIC FEVER.
AB  - The question of the relationship of streptococci to the etiology of infectious
      arthritis and of rheumatic fever is of the utmost importance. If a streptococcus
      or group of streptococci could be shown to be associated See PDF for Structure
      with either disease, some form of specific treatment might be available. The
      possibility of primary streptococcic infection as the cause of rheumatic fever,
      and, to a less extent, of acute infectious arthritis would seem to be a
      reasonable conjecture because of the frequency of associated throat, sinus or
      other focal infection. To consider that these same streptococci remain in or
      about the affected joint and to such an extent that they are found in the blood
      stream in cases of chronic infectious arthritis of years' duration demands a
      rather unique conception. Recent investigative work has certainly tended to
      confirm the importance of streptococci in these diseases, but, if all the
      published reports are considered as a group, one can not help being impressed
      with the inconsistency and peculiarities of the findings. In blood cultures from
      cases of rheumatic fever Clawson (7) recovered Streptococcus viridans, Small (8)
      and Birkhaug (9) non-hemolytic (gamma type) streptococci, and Cecil et al. (3)
      Streptococcus viridans, rarely hemolytic and non-hemolytic streptococci. In blood
      cultures from cases of infectious arthritis Cecil et al. (2) recovered attenuated
      hemolytic streptococci and occasionally Streptococcus viridans, non-hemolytic
      streptococci and diphtheroids and Margolis and Dorsey (10) green-producing and
      indifferent streptococci and diphtheroids, whereas from synovial fluids and
      regional lymph nodes Forkner, Shands and Poston (4) and Poston (5) obtained
      Streptococcus viridans and Margolis and Dorsey (11) recovered green-producing and
      indifferent streptococci and diphtheroids from epiphyseal marrows, bones and
      synovial membranes. On the other hand, Jordan (12) and Nye and Seegal (13) and
      the work reported in this paper have failed to confirm these findings. If a
      streptococcus is the infective agent, it is difficult to explain why the
      organisms recovered so consistently by certain groups of investigators are so
      different and why the findings of other groups are entirely negative. The chances
      of contamination, even with the most careful manipulation, are extremely
      favorable when using a cultural technique which demands subculturing a fluid
      medium every 3 to 5 days for a period of 4 to 6 weeks. The question arises as to
      what organisms should be considered as contaminants. Cultures found to contain
      Staphylococcus albus have never been judged significant. Margolis and Dorsey (11)
      have excluded Gram-positive bacilli from their series, but have included
      diphtheroids. Cecil et al. (2) reported the recovery of diphtheroids and
      Micrococcus zymogenes from blood cultures which they did not consider
      contaminated. Jordan (12) recovered short Gram-negative bacilli and Gram-positive
      bacilli and questioned their importance. The occurrence of such bacteria would
      appear to be not unlike that of the non-hemolytic (gamma type) streptococci
      reported by Small (7), Birkhaug (9) and, rarely, by Cecil et al. (2) and Margolis
      and Dorsey (10,11). In the work reported in this paper and in previously
      published work (13) with blood cultures from cases of rheumatic fever,
      staphylococci, Gram-positive bacilli and diplococci and diphtheroids have been
      isolated from a certain number of the cultures. Since these were found, as a
      rule, in only 1 of 2 or more cultures from the same blood and since such
      organisms occurred about as frequently in cultures from control cases, they have
      been considered merely contaminants. The findings in the 9 cases of arthritis
      with positive blood cultures reported by Margolis and Dorsey (10) are certainly
      far from convincing. These authors found green-producing streptococci in 5 of the
      9 cases, but duplicate cultures on the same blood, with one exception, were
      always negative and the two repeat cultures were negative. Furthermore, in the 3
      cases yielding indifferent streptococci in one subculture all subsequent
      subcultures were negative. In the work reported in this paper a green-producing
      and a non-hemolytic streptococcus were isolated from blood cultures, but a Gram
      positive diplococcus and a Gram-positive bacillus, respectively, were recovered
      from the same cultures. A consideration of the above would seem to point to the
      probability, even certainty, of streptococci occurring in some cultures as
      contaminants; and the work of Olitsky and Long (14) and Long, Olitsky and Stewart
      (15) has clearly demonstrated that the air contamination of cultures of ground
      material with non-hemolytic green-producing streptococci can occur just as easily
      as with diphtheroids and staphylococci. It is obvious, in such cases, that the
      types of organisms recovered are dependent on the flora of the air of the
      laboratory or of the throat of the laboratory worker, and this point may well
      explain the differences in the cultural findings under consideration. A number of
      years ago numerous articles (16-19) appeared relative to the bacteriologic flora
      of lymph nodes, particularly those from cases of Hodgkin's disease, and it is
      interesting to note that the organisms recovered were quite similar to those
      which have been recovered from the blood and tissues of cases of arthritis and
      rheumatic fever, with the exception that the diphtheroids were, at that time,
      much more in prominence. Regardless of elaborate serological studies and animal
      experiments, streptococci must be recovered consistently by several groups of
      laboratory workers before their etiologic role in chronic arthritis and rheumatic
      fever can be accepted. Duplicate cultures and repeat cultures should yield the
      same organism in a generous percentage of cases and cultures from cases of other
      diseases or from normal persons should be negative. Positive cultures from
      duplicate cultures opened only at the time when the first culture showed growth
      would make the findings more significant than if the whole series were
      subcultured every 3 to 5 days. The work of Cecil, Nicholls and Stainsby on the
      bacteriology of the blood and joints in chronic arthritis and rheumatic fever has
      apparently been carried out most carefully and thoroughly and their results are
      very consistent and convincing. In spite of attempts to follow their methods in
      the selection of patients and in cultural technique, the results on the
      relatively small series of cases which are reported here fail to confirm their
      findings.

PMID- 19869812
TI  - CHEMICAL AND IMMUNOLOGICAL PROPERTIES OF A SPECIES-SPECIFIC CARBOHYDRATE OF
      PNEUMOCOCCI.
AB  - Pneumococci contain a non-protein constituent which, on the basis of its chemical
      and immunological properties, appears to be a carbohydrate distinct from the type
      specific carbohydrate and common to the species.

PMID- 19869813
TI  - THE ROLE OF MICROBIC VIRULENCE, DOSAGE, AND HOST RESISTANCE IN DETERMINING THE
      SPREAD OF BACTERIAL INFECTIONS AMONG MICE : I. PASTEURELLA LEPISEPTICA AND
      PASTEURELLA AVISEPTICA INFECTIONS.
AB  - 1. Three strains of Pasteurella native to rabbits, introduced into mouse
      communities failed to spread or survive. 2. One strain of fowl Pasteurella, so
      introduced, survived for 2 months without causing death, after which, it gave
      rise to a 5 day epidemic, fatal to 77 per cent of the population. Subsequently,
      no further deaths from this source occurred and the strain died out completely.
      3. At the height of the epidemic, caused by the fowl strain of Pasteurella, 6
      cultures were obtained which, on direct inoculation, proved to have a degree of
      virulence for mice and rabbits equal among themselves and the same as the strain
      originally employed.

PMID- 19869814
TI  - THE ROLE OF MICROBIC VIRULENCE, DOSAGE, AND HOST RESISTANCE IN DETERMINING THE
      SPREAD OF BACTERIAL INFECTIONS AMONG MICE : II. B. FRIEDLAENDERI-LIKE INFECTION.
AB  - 1. In September, 1925, explosive and highly fatal epidemics of a Friedlander-like
      bacillus infection arose in three of four experimentally controlled mouse
      populations. In the populations to which daily additions were made,
      characteristic secondary waves ensued. These waves appeared at definite
      population levels, lasted a definite number of days, and reduced the population
      to a definite low census. Subsequently, endemic periods intervened, followed by
      the disappearance of the disease during March, 1926. 2. In August, 1926, renewed
      epidemics of the infection arose in all four populations. These outbreaks
      resembled one another but were more enduring than the preceding ones. Moreover,
      fewer secondary waves followed, and the disease disappeared in February, 1927. 3.
      The virulence or disease-producing power of the Friedlander-like organisms, as
      determined by the ability to spread and induce typical epidemics among
      populations of previously unexposed mice, and by direct inoculation titrations
      remained constant during pre-epidemic, epidemic, post-, and inter-epidemic phases
      of the infection. 4. The Friedlander-like organisms were not recovered in
      cultures from bedding, food, or feces, but they were obtained from the nasal
      passages. Mice harboring the organisms usually died within a few days of the
      test; a few, however, survived and ceased to be carriers. The carrier rate in a
      given community was found to increase prior to epidemic outbreaks and to decrease
      shortly before the time of peak mortality. 5. The substitution of relatively
      susceptible for "standard" immigrants in a population was followed by an increase
      in severity and spread of the disease, whereas a substitution of "standard" for
      resistant immigrants was followed by a fall in severity and extent of disease.

PMID- 19869815
TI  - THE ROLE OF MICROBIC VIRULENCE, DOSAGE, AND HOST RESISTANCE IN DETERMINING THE
      SPREAD OF BACTERIAL INFECTIONS AMONG MICE : III. B. ENTERITIDIS INFECTION.
AB  - 1. Several mouse populations under experimental observation were infected with B.
      enteritidis typhoid. The infection took the form of periods of low grade
      mortality interspersed with epidemiform outbreaks. During the periods of low
      grade mortality, the number of daily deaths was either relatively constant or
      rhythmic in 9 day intervals. The epidemiform outbreaks were associated invariably
      with some definite environmental disturbance. 2. The spread of this infection was
      not influenced by the presence of bacteriophage or the bacterial-dissociation
      phenomena. 3. The virulence or disease-producing power of B. enteritidis was
      found to be constant during all pre-epidemic, epidemic, and endemic phases of the
      infection. 4. The dosage of B. enteritidis available to a population at a given
      time was found to vary directly with mortality at a time difference approximating
      that of the incubation period of the disease. 5. The amount and severity of B.
      enteritidis infection in the populations were controlled experimentally by
      varying the diet from adequate to optimum constituents and by varying the daily
      immigrants from a relatively resistant to a susceptible race of mice.

PMID- 19869816
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : XII. THE FIXATION FOR
      HISTOLOGICAL PURPOSES OF ERYTHROLITMIN AFTER VITAL STAINING, WITH A NOTE ON THE
      DISTRIBUTION OF THE INDICATOR.
AB  - A method for fixing erythrolitmin in tissues for subsequent histological
      examination is described. Some features are recorded of the distribution of the
      indicator in animals receiving it in large quantity.

PMID- 19869817
TI  - THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES : XIII. THE REACTION
      PREVAILING DURING THE AUTOLYSIS IN VIVO OF SMALL TISSUE MASSES.
AB  - By a variety of methods necrosis of individual cells was produced in the living
      animal. Cell death was found to be clearly perceptible by means of the changes in
      the color of segregated erythrolitmin at a time when it was not as yet
      recognizable by ordinary histological methods. The hue of the dye pointed to an
      alteration in the direction of alkalinity; but the extent of this could not be
      determined owing to the limited range of the indicator Cartilage damaged by
      freezing in situ becomes alkaline, its reaction now approximating that of the
      blood. The findings support the view that within the body the autolysis of
      individual cells and of small tissue masses may take place under the
      circumstances of a slight alkalinity.

PMID- 19869818
TI  - THE INFLUENCE OF URIC ACID ON THE PERMEABILITY OF MEMBRANES.
AB  - 1. Congo red injected in vivo together with uric acid gives rise to more intense
      and diffuse red coloring in rats, especially in the subcutaneous and peri
      articular tissues, than is the case in control rats injected simply with dye. 2.
      Uric add added in vitro to solutions of Congo red or trypan blue increases the
      speed of diffusion of these dyes, both through gelatin and the animal membranes
      (dialyzers). These results support a view long maintained by Professor Rondoni
      (25), namely, that some factor of an endothelial-capillary nature must be taken
      into consideration in manifestations of hyperuricemia and of gout.

PMID- 19869819
TI  - FACTORS WHICH DETERMINE RENAL WEIGHT : XI. RENAL FUNCTION.
AB  - THE AMOUNT OF FUNCTIONING RENAL TISSUE AS MEASURED BY THE WEIGHT OF THE KIDNEYS
      IN THE ALBINO RAT IS DIRECTLY PROPORTIONAL TO THE RENAL FUNCTION AS MEASURED BY
      THE RATIO: See PDF for the structure under certain special conditions.

PMID- 19869820
TI  - A CEREBELLAR DISORDER IN CHICKS, APPARENTLY OF NUTRITIONAL ORIGIN.
AB  - Growing chicks maintained on a diet consisting of milk powder, casein, starch,
      yeast, cod liver oil, salts and filter paper develop ataxia, tremors, retraction
      or twisting of the head, clonic spasms of the legs, and stupor. These symptoms
      may appear suddenly, usually between the 18th and 25th day, and may end in death.
      If recovery takes place, the chicks may go on to normal development. Definite
      lesions are found in the cerebellum of the affected chicks. These consist of
      edema, necrosis and hemorrhages. Hyaline thrombi are found in the capillaries in
      and about the degenerated areas.

PMID- 19869821
TI  - IMMUNITY FOLLOWING THE INJECTION OF MONKEYS WITH MIXTURES OF POLIOMYELITIS VIRUS
      AND CONVALESCENT HUMAN SERUM.
AB  - 1. Experiments are reported on the use of poliomyelitis virus neutralized by
      specific antiserum as an agent to induce active immunity against the experimental
      disease in monkeys. 2. The results indicate that protection can be conferred upon
      a certain number of the treated animals. 3. The neutralized material gave rise in
      no instance to symptoms of disease in the treated monkeys. 4. Active
      poliomyelitis virus, suitably neutralized by admixture with convalescent serum,
      was without pathogenic effect when given by repeated nasal instillations.

PMID- 19869822
TI  - EXPERIMENTAL STUDY OF A HORSE ANTIPOLIOMYELITIC SERUM.
AB  - Through the kindness of Dr. W. H. Park we have been enabled to study a horse
      antipoliomyelitic serum. This preparation has been supplied us in three forms:
      citrated blood plasma, serum, and globulin concentrate. We have tested these
      preparations in vitro and in vivo for inactivating or neutralizing or, to use
      perhaps a better term, antiviral effects against a constant, potent, filtrate
      virus of poliomyelitis. The preparations exhibited these effects when combined in
      vitro. Their action in this respect appears to be greater and more constant than
      that found by Stewart and Haselbauer for the Pettit antipoliomyelitic horse
      serum. On the other hand, in vivo tests carried out by us were less successful.
      In comparison with the constancy of action, under given conditions, of
      convalescent monkey and human sera, the antipoliomyelitic horse serum displayed
      striking irregularity, and certain preparations were devoid of protective power.
      The precise nature of the inactivating substances in the horse antiserum and
      their relation to the corresponding substances in convalescent sera have still,
      to be determined. As far as one absorption test carried out by us indicates,
      precipitin does not play a major role in the inactivating process. When an active
      globulin concentrate was filtered through Berkefeld candles, it lost its in vitro
      inactivating power. This is not true of convalescent sera in the native state. No
      tests have, however, been made with globulin concentrates from such sera. The
      experiments described in this paper raise the question whether, therapeutically
      considered, the antipoliomyelitic horse serum should be regarded as an exact
      equivalent of, and hence employed as a perfect substitute for, convalescent
      serum. This question can only be answered by further experiment and observation.

PMID- 19869823
TI  - REINFORCEMENT OF CONVALESCENT ANTIPOLIOMYELITIC SERUM IN THE MONKEY.
AB  - A comparison has been made of the neutralizing value of pooled convalescent
      monkey serum for the filtered virus of poliomyelitis, before and after a series
      of reinforcement injections of the same virus strain. The strength of the pooled
      convalescent serum is increased by the reinforcing procedure. The original monkey
      convalescent serum had a neutralization value much below that of a pooled human
      convalescent serum. By reinforcement the neutralization value of the monkey serum
      was brought approximately to that of the human serum. One sample of serum from a
      supposedly normal child of 8 years exhibited a neutralizing value approximately
      equal to that of a pooled human convalescent serum and the reinforced pooled
      monkey serum.

PMID- 19869824
TI  - ABSORPTION FROM THE PERICARDIAL CAVITY.
AB  - 1. Physiological salt solution is absorbed from the pericardial cavity of medium
      sized rabbits at a rate of approximately 1.3 cc. per hour. This absorption is via
      the subepicardial blood capillaries. 2. Rabbit serum and horse serum are absorbed
      extremely slowly-an indication of the low-grade lymphatic drainage of the
      pericardial sac. 3. Graphite particles of bacterial dimensions are also removed
      very slowly. Such particles enter lymphatics only after phagocytosis. The
      lymphatics in the basal part of the pericardium are the principal source of
      drainage. Subepicardial lymphatics are entered with difficulty from the
      pericardial cavity.

PMID- 19869825
TI  - THE GERMICIDAL ACTION OF alpha-MERCAPTO AND alpha-DISULFO SOAPS.
AB  - 1. Certain of the alpha-mercapto soaps and alpha-disulfo soaps are powerful
      germicides. 2. In the alpha-mercapto series, those soaps with 12 and 14 carbon
      atoms are most germicidal. In the disulfo series, the dicaprate, dilaurate, and
      dimyristate are most germicidal. The optimum number of carbon atoms varies with
      the test organism used. 3. These soaps, like others previously studied, show a
      markedly selective germicidal action.

PMID- 19869826
TI  - THE ACTION OF TESTICLE, KIDNEY, AND SPLEEN EXTRACTS ON THE INFECTIVE POWER OF
      BACTERIA.
AB  - The addition of testicle extract to cultures of 20 different bacteria just prior
      to inoculation enhances their infectious activity to a high degree. Kidney
      extracts enhance the infections of staphylococci to a less degree than testicle
      extracts, while spleen extracts never give rise to enhancement, and often cause
      the lesion to be less than would ordinarily be the case.

PMID- 19869827
TI  - THE EFFECT OF TESTICULAR EXTRACT ON FILTERABLE VIRUSES.
AB  - The Reynals factor promotes the pathogenic action of the viruses of herpes,
      vesicular stomatitis of horses, Borna disease, and vaccinia. The heightening of
      virulence is revealed in various ways. The effects of the viruses may be
      accentuated; or a weak strain converted into a strong one, as in the case of the
      F. strain of herpes virus; or the power acquired to infect resistant species or
      tissues, as, e.g., rabbits and the abdominal skin of guinea pigs, with acute
      vesicular stomatitis. The Reynals factor should serve as an important agent in
      the study of filterable viruses.

PMID- 19869828
TI  - A STUDY OF THE TOXIC PROPERTIES OF TUBERCULO-PROTEINS AND POLYSACCHARIDES.
AB  - The temperature reaction in tuberculous and normal guinea pigs and rabbits is
      elicited by the tuberculo-protein and probably not at all by the polysaccharides.
      The polysaccharides may have some killing power under certain conditions, but
      this is not as consistently related to dosage as in the case of the proteins.
      Both proteins and polysaccharides cause a change in the white blood cells when
      introduced by any route.

PMID- 19869829
TI  - THE OCCURRENCE OF SEASONAL VARIATIONS IN THE GOITER OF RABBITS PRODUCED BY
      FEEDING CABBAGE.
AB  - The evidence presented indicates that cabbage maturing in the spring and summer
      months has little goiter-produdag power. Cabbage maturing in the late autumn has
      much greater goiter-produdng power, although this shows considerable variation in
      different years. It has not been possible to correlate available meteorological
      data with these variations.

PMID- 19869830
TI  - ON THE PRESENCE IN ANTIPNEUMOCOCCUS SERUM OF TYPE-SPECIFIC PROTECTIVE ANTIBODY
      NOT NEUTRALIZED BY HOMOLOGOUS SPECIFIC SOLUBLE SUBSTANCE.
AB  - The mutual relationship of the anticarbohydrate precipitins and the protective
      action in antipneumococcus sera to the soluble specific substance was
      investigated. The assumption is made that there exists in antipneumococcus serum,
      type-specific protective antibody which is distinct from the anticarbohydrate
      precipitins and is not neutralized by the soluble specific substance. This
      assumption is based upon the following observations in experiments which were
      conducted primarily with Type I antipneumococcus horse serum. 1. Lack of
      proportionality between the quantity of SSS added and the amount of
      anticarbohydrate precipitin and protective action neutralized. 2. Protective
      capacity of specific precipitates (SSS-precipitin complex) is accounted for on
      the basis of a liberation of non-specifically adsorbed protective antibody. 3.
      SSS only partially neutralizes the protective action of antipneumococcus serum in
      vivo. 4. Type-specific protective antibody remains in antipneumococcus serum
      after complete precipitation of the anticarbohydrate precipitins. 5. This
      residual type-specific protective antibody is not neutralized by additional SSS
      nor by absorption with heterologous pneumococci; it is definitely absorbed by the
      homologous pneumococci.

PMID- 19869831
TI  - CERTAIN ASPECTS OF MOUSE PROTECTION TESTS FOR ANTIBODY IN PNEUMOCOCCUS PNEUMONIA.
AB  - 1. Though in general in pneumococcus pneumonia the appearance of protective
      substance coincides rather sharply with the fall in the temperature, antibody may
      appear spontaneously in the blood serum as early as the 3rd or 4th day and crisis
      and recovery may be delayed until the 6th to the 10th day. 2. Recovery at times
      occurs without demonstrable protective substance in the blood in patients who
      later develop protection. 3. The amount of antibody developed in the course of
      pneumococcus pneumonia is small and in the majority of cases tested was
      insufficient to protect against more than 100 lethal doses of homologous
      pneurnococci and never against more than 10,000 lethal doses. 4. Treatment with
      Felton's antibody late in the course of the disease materially increases the
      amount of protective substances in the blood. A high degree of protection may be
      established by treatment in fatal cases. After the 3rd day doses of more than
      200,000 Felton units are usually necessary to produce a greater degree of
      protection than might otherwise be expected. 5. The formation of protective
      substances by the patient himself is not an assurance against progress of the
      infection to a fatal termination. 6. Protective substance in the blood and
      pneumococcic septicemia may occur simultaneously.

PMID- 19869832
TI  - AN ACCELERATED FEBRILE REACTION IN MONKEYS UPON REINOCULATION WITH POLIOMYELITIS
      VIRUS.
AB  - 1. Primary poliomyelitic infection in the monkey, as a rule, is characterized by
      no significant increase in the body temperature during the incubation period
      until 48 or 24 hours before the onset of clinical symptoms, when a critical rise
      of the temperature occurs. 2. The temperature curve of recovered monkeys on
      intracerebral reinoculation shows an almost immediate and marked febrile reaction
      during the first 24 or 48 hours after inoculation. A similar accelerated febrile
      reaction may be obtained in recovered animals after subcutaneous injection of
      killed virus. In case the previous infection is of very recent date,
      reinoculation may lead to no demonstrable reaction whatsoever. 3. Monkeys, which
      have received a number of parenteral injections of live virus, respond to
      intracerebral infection with a precocious and prolonged febrile reaction on the
      3rd or 4th day after infection which may last until the onset of symptoms. 4. The
      altered response to reinoculation of monkeys which have previously been in
      contact with the virus, suggests a close analogy with the accelerated reactions
      observed in allergic phenomena.

PMID- 19869833
TI  - STUDIES ON INFLAMMATION : V. THE MECHANISM OF FIXATION BY THE INFLAMMATORY
      REACTION.
AB  - Microscopic studies show the presence of a network of fibrin within the tissues
      and numerous thrombosed lymphatics at the site of inflammation. Precipitated iron
      compounds, possibly coagulated horse serum, or particulate matter caught in this
      fibrinous reticulum will disseminate less readily than trypan blue from the site
      of inflammation. Trypan blue injected at the periphery of an inflamed area fails
      to enter the site of inflammation. This failure of penetration is caused by the
      occlusion of lymphatic vessels and by the presence of a fine network of fibrin in
      the tissue spaces of the inflamed area. Fixation of foreign substances by the
      inflammatory reaction is therefore primarily due to mechanical obstruction caused
      by a network of fibrin and by thrombosed lymphatics at the site of inflammation.
      There is another phase of the problem which still requires more accurate
      information. This concerns the relation between exudation from blood vessels and
      changes in flow of lymph from the inflamed area. Further experiments are being
      conducted to investigate this question. The reaction of fixation which occurs
      extremely early in the inflammatory process circumscribes the irritating
      substance and allows a definite period of time for the leucocytes to assemble for
      the purpose of phagocytosis. It is through a delicate regulating mechanism of
      this kind that, to use the expression of Opie (7), "the vital organs are
      protected at the expense of local injury."

PMID- 19869834
TI  - STUDIES ON INFLAMMATION : VI. FIXATION OF TRYPAN BLUE IN INFLAMED AREAS OF FROGS.
AB  - Trypan blue injected into the circulating blood stream of frogs accumulates
      rapidly in an inflamed area. When trypan blue is injected directly into the area
      of inflammation it is fixed in situ and fails to diffuse outward. If the dye is
      injected at the periphery of an inflamed area it fails to enter the site of
      inflammation. This failure of penetration is caused by the occlusion of lymphatic
      vessels and the presence of a network of fibrin in the inflamed area. These
      experiments furnish additional evidence that fixation of foreign substances by
      the inflammatory reaction is due to mechanical obstruction caused by a network of
      fibrin and by thrombosed lymphatics at the site of inflammation.

PMID- 19869835
TI  - IMMUNIZATION AGAINST VACCINIA BY NON-INFECTIVE MIXTURES OF VIRUS AND IMMUNE
      SERUM.
AB  - 1. Vaccine virus and specific immune serum mixed in such proportions as to
      produce no lesion when inoculated intradermally induce immunity when instilled
      into the nasal cavities of rabbits. 2. The mixture is also effective when
      inoculated subcutaneously. 3. Immunity is brought about with a minimum of
      systemic reaction and no local one. 4. When the mixtures are incompletely
      neutralized generalized vaccinia results.

PMID- 19869836
TI  - THE GRADIENT OF VASCULAR PERMEABILITY : II. THE CONDITIONS IN FROG AND CHICKEN
      MUSCLE, AND IN THE MAMMALIAN DIAPHRAGM.
AB  - A mounting gradient of permeability exists along the capillaries of frog muscle.
      In chicken muscle on the other hand none has been demonstrated; but the close
      knit vascularization is arranged in duplicate in such manner that the blood runs
      in opposite directions through the capillaries of nearly adjacent fibres. In a
      flight muscle of the pigeon there exists in addition to this artifice what
      appears to be a special collecting system of venous capillaries. In the mammalian
      diaphragm indications of such a system are also to be found, and a gradient of
      capillary permeability like that in the other skeletal muscles is probably
      present. These vascular conditions are briefly considered in terms of function.

PMID- 19869837
TI  - THE GRADIENT OF VASCULAR PERMEABILITY : III. THE GRADIENT ALONG THE CAPILLARIES
      AND VENULES OF FROG SKIN.
AB  - A steeply mounting gradient of permeability is demonstrable along the meshwork of
      capillaries which connects the arterioles and venules of the skin of the frog.
      The venules incorporated in the meshwork are even more permeable than the
      capillary meshes giving into them. The presence of the gradient under such
      differing conditions as exist along frog and mammalian capillaries enables one to
      rule out certain factors which might be invoked to explain it; and it is not
      explainable in terms of those influences generally recognized as conditioning
      exchange between the blood and tissues. Not improbably it results from a
      structural differentiation along the capillary.

PMID- 19869838
TI  - OBSERVATIONS WITH A NEW TRANSMISSIBLE STRAIN OF THE LEUCOSIS (LEUCEMIA) OF FOWLS.
AB  - Myeloid leucosis and erythroleucosis can be transmitted from one bird to others
      by emulsions of infiltrated organs, whole blood cells, and plasma. Inoculation is
      more often successful with blood cells or with whole blood than with plasma or
      with emulsions of organs infiltrated as the result of leucosis. Inoculation with
      material from a bird with myeloid or with erythroleucosis produces both myeloid
      and erythroleucosis, and in many instances mixed forms with characters of both.
      Evidence is wanting that lymphoid leucosis is caused by the agent that transmits
      myeloid and erythroleucosis. The occurrence of lymphoid leucosis among the birds
      inoculated with material from myeloid or erythroleucosis may be explained as
      spontaneous disease. Injury to cellular structure by treatment with distilled
      water or by repeated freezing and thawing does not destroy the agent that
      transmits the disease. Berkefeld filtrates have failed to transmit regularly
      myeloid or erythroleucosis. The evidence obtained shows, however, that the
      transmissible agent is filterable, although there are technical difficulties in
      its filtration.

PMID- 19869839
TI  - TRANSMISSION EXPERIMENTS WITH LEUCOSIS OF FOWLS.
AB  - It is shown, in a carefully controlled experiment, that fowl leucemia can be
      readily transmitted from chicken to chicken by injection. Of 25 fowls, 13 were
      injected intravenously with blood from a chicken (No. 575) with erythroleucosis
      and 12 with blood from a chicken (No. 689) with myeloid leucosis. The injected
      birds and an equal number of uninjected controls were kept in tiers of
      alternating cages under as nearly identical conditions as possible. The donors,
      the controls, and the injected birds were all of the same stock and of the same
      age. In the two series 13 or 52 per cent of the 25 fowls inoculated developed
      leucemia within 4 to 10 weeks after injection. The two types of leucemia,
      erythroleucosis and myeloid leucosis, developed in both groups irrespective of
      the type used for injection. Among the uninjected controls no cases of
      erythroleucosis or of myeloid leucosis were observed. Lymphoid leucosis occurred
      in one injected fowl but since it also occurred in one control it may be assumed
      that it was probably not caused by the injected material.

PMID- 19869840
TI  - HISTOLOGICAL STUDIES ON HOG CHOLERA : I. LESIONS IN THE CENTRAL NERVOUS SYSTEM.
AB  - 1. A more or less marked encephalomyelitis and meningitis was found in 33 out of
      39 cases of virus hog cholera which had been infected either intramuscularly or
      by contact and killed between 6 and 49 days after infection. 2. This hog cholera
      encephalitis is characterized by a varying amount of vascular and perivascular
      infiltration with small lymphocytes, mononuclear elements, a few plasma cells,
      and occasionally a few eosinophilic leucocytes. The glia shows a proliferation
      surrounding infiltrated vessels or forming small nodules or more diffuse foci.
      Satellitism and in a few instances true neuronophagia have been observed. Both
      microglia and macroglia participate in this process. There is no essential
      increase of glia fibers. In nearly all parts of the central nervous system
      degenerating lesions of the nerve cells such as tigrolysis and degeneration of
      the nucleus, including a slight atrophy of endocellular neurofibers, are
      encountered. No demyelinization has been observed. Specific inclusion bodies in
      the nerve cells are absent. In addition, in a certain number of cases microscopic
      and macroscopic hemorrhages are present in the brain, spinal cord, and meninges.
      3. These lesions in varying degrees have been found in swine infected with four
      different strains of hog cholera virus. Two were laboratory strains and two were
      obtained from fresh field outbreaks. 4. Histological changes in the central
      nervous system were found as early as 6 days after infection before the animal
      showed central nervous system symptoms. In two cases which were paralyzed no
      lesions in the central nervous system could be demonstrated. 5. The lesions in
      the central nervous system are considered to be the anatomical substratum for the
      various nervous symptoms commonly found in hog cholera.

PMID- 19869841
TI  - A CRITERION OF HEMORRHAGIC DIATHESIS IN EXPERIMENTAL SCURVY.
AB  - 1. The degree of scorbutic change in the vessels of animals with experimental
      scurvy can be roughly measured by establishing the amount of negative pressure
      required to produce petechial hemorrhages in the skin. 2. The test shows that the
      hemorrhagic diathesis in experimental scurvy develops earlier than any other
      known sign of the disease and that it persists in some degree throughout. 3. The
      response of the blood vessels to the administration of antiscorbutic substances
      is extremely rapid as shown by the test, but it varies with the amount of
      antiscorbutic given and its method of administration. 4. The changes in the
      resistance of the vessels follows a curve which rises towards recovery during the
      end of the 1st week on a scorbutic diet, reaches a peak in the 2nd week and then
      falls steadily during the remainder of the course of the disease. This indicates
      that the course of the disease is not constant and progressive. 5. The test may
      have clinical value in the diagnosis of scurvy.

PMID- 19869842
TI  - THE PRECIPITIN REACTION OF ANTIPNEUMOCOCCUS SERA : III. THE RATIO OF PRECIPITIN
      TO PROTECTIVE ANTIBODY IN TYPE II.
AB  - The ratio precipitin/protective antibody is given for several fresh
      antipneumococcus horse sera (Type II). The application of the precipitin test
      here dealt with and that of similar ones, based on the conception of a
      parallelism between precipitin and protective antibody, is limited to unrefined
      horse sera.

PMID- 19869843
TI  - THE NUMBER OF OPEN GLOMERULI IN ACUTE MERCURIC CHLORIDE NEPHROSIS.
AB  - Acute mercurial nephrosis in the rabbit is not associated with a decrease of
      glomerular circulation.

PMID- 19869844
TI  - STUDIES ON PARATYPHOID C BACILLI ISOLATED IN CHINA.
AB  - A brief clinical history of five patients from whom paratyphoid C was isolated
      and a description of the cultures are given. It is pointed out that the purely
      non-specific forms are more nearly related to the hog cholera bacillus than are
      those containing both specific and non-specific forms.

PMID- 19869845
TI  - COMPENSATORY HYPERTROPHY OF THE SPLEEN.
AB  - Following the removal of half of the spleen in young adult rats there is a
      compensatory enlargement of the remaining portion of about 50 per cent while in
      mature rabbits no such compensatory hypertrophy follows a similar procedure. It
      is uncertain whether this difference is due to a difference in the function of
      the spleen in the two species or to the fact that the rats were infected with
      Bartonella muris while the rabbits were not.

PMID- 19869846
TI  - STUDIES ON TYPHUS FEVER : V. ACTIVE IMMUNIZATION AGAINST TYPHUS FEVER WITH
      FORMALINIZED VIRUS.
AB  - We have adduced evidence that guinea pigs can be completely or partially
      protected by three injections of typhus tunica material in which there are
      moderate numbers of Rickettsiae, treated for from 24 to 48 hours with a 0.2 per
      cent formalin solution. We believe that the immunization is due to the presence
      of the Rickettsiae, since in our preceding experiments we have satisfied
      ourselves that these organisms are the true etiological factors of the disease.
      For the reasons stated above, we believe that the formalinized vaccine does not
      contain living, but attenuated organisms, and that the immunizing effect is the
      result of treatment with formalin-killed Rickettsiae. This point, however, we
      admit, is not absolutely determined. These experiments, together with the results
      obtained in the concentration of Rickettsia material by the diet method of
      reducing resistance as described in the paper which follows, furnish a hopeful
      method and a reasonable theoretical basis for a procedure of active immunization
      against this disease in human beings.

PMID- 19869847
TI  - STUDIES ON TYPHUS FEVER : VI. REDUCTION OF RESISTANCE BY DIET DEFICIENCY.
AB  - The above experiments demonstrate that guinea pigs and rats subjected to vitamin
      deficient diets to a point at which deficiency symptoms appear, and then
      inoculated with typhus virus, exhibit clinical pictures which indicate a far more
      severe infection than that observed in normal animals after inoculation. There is
      also a wider distribution of Rickettsiae and a concentration of organisms which,
      in pleural and peritoneal exudates, amounts to almost cultural proportions.
      Important from our point of view is the fact that these experiments furnished a
      step toward the accomplishment of our purpose, which was to obtain amounts and
      concentrations of Rickettsiae suitable for immunological studies until such a
      time when tissue culture may have developed to a practically useful stage. The
      experiments are of immediate importance in that they furnish us a method for
      improving our technique of active immunization reported upon in the preceding
      paper, No. V (8). From the epidemiological point of view these experiments at
      least suggest an explanation of one of the important factors which enter into the
      historical association of high typhus mortality with war and famine.

PMID- 19869848
TI  - ON THE NATURE OF THE CHILL-PRODUCING PRINCIPLE IN ANTIPNEUMOCOCCUS SERUM.
AB  - 1. By means of a test method, which is described, the presence or absence of the
      chill-producing principle in antipneumococcus serum may be determined. 2. This
      principle may be present in normal blood or serum, homologous as well as
      heterologous, and the measures employed to obtain an antibody solution are not
      essential factors in its formation. 3. The chill reaction may be mitigated by the
      administration of nitrites and by opium and antipyretics. It is doubtful whether
      this fact offers any practical therapeutic application. 4. The reaction has no
      relationship to anaphylaxis or to certain toxic effects of drawn blood which have
      been studied by Freund, Starling and others. 5. The chill-principle appears to be
      formed only in blood which has been allowed to stand. Our experiments do not show
      that the reaction is dependent on formed elements, fibrinogen, or lipoids. 6.
      Anticoagulants, filtration, dialysis and moderate heating are without effect in
      removing the principle from the solution containing it. 7. By changes in the
      sodium chloride and hydrogen ion concentration in antibody solutions an acid
      globulin and an alkaline globulin fraction may be obtained. The acid globulin
      fraction, whether or not phospholipin is present, contains the greater part of
      the chill-principle and a small part of the antibody substance; the alkaline
      globulin fraction contains the greater part of the antibody substance and a
      smaller part of the chill-principle. The acid globulin fraction is not itself the
      chill-principle but serves as a carrier of this, probably through an adsorptive
      process.

PMID- 19869849
TI  - FURTHER EXPERIENCES WITH NON-SPECIFIC LOCAL CUTANEOUS IMMUNITY TO STAPHYLOCOCCUS
      AUREUS : LOCAL NON-SPECIFIC PROTECTION.
AB  - 1. Many substances besides the specific broth filtrates of Besredka can be
      utilized as topical applications to protect guinea pigs from the effects of
      massive doses of staphylococcus given subcutaneously. (Plain broth, peptone 10
      per cent, peptone 1 per cent, Liebig's meat extract, mustard plaster and normal
      horse serum.) 2. Where such protection occurs, no matter what the stimulus is,
      the local skin reaction microscopically is the same as that previously described
      for broth compresses. 3. Many topical applications of such substances as saline,
      water, plain compresses, etc., may confer slight protection on an animal. 4.
      Specific filtrates (Besredka) confer no protection on the experimental animal if
      applied at the time of inoculation or thereafter. 5. The local protection
      described in our experiments is non-specific in its nature.

PMID- 19869850
TI  - FURTHER OBSERVATIONS ON THE SURVIVAL OF VACCINE VIRUS SEPARATED FROM LIVING HOST
      CELLS BY COLLODION MEMBRANES.
AB  - The survival of vaccine virus when incubated on the opposite side of a collodion
      membrane from a suspension of fresh minced rabbit kidney was not complete in
      these experiments, and passage in series was not successful. The degree of
      survival seemed somewhat greater if dead cells, killed by repeated freezing and
      thawing, were added to the virus during incubation, although the tissue was able
      to increase the intensity of the skin reactions. Extracts of dead kidney cells
      did not increase the degree of survival, as determined by the intensity of the
      skin reaction. No significant or constant increase in the intensity of the skin
      reactions resulted from the addition of cysteine hydrochloride to the virus in
      the dialyzing apparatus.

PMID- 19869851
TI  - THE INFLUENCE OF TESTICLE EXTRACT ON THE INTRADERMAL SPREAD OF INJECTED FLUIDS
      AND PARTICLES.
AB  - The experiments in this paper show that testicle extract causes India ink
      particles and those of Prussian blue to spread much more extensively through the
      intercellular spaces than similar suspensions made with Ringer's solution.
      Methylene blue inoculated intravenously localizes more extensively in areas
      previously injected with testicle extracts than in control areas receiving
      injections of tissue extracts without enhancing power. Kidney extracts have this
      property to a less degree, whereas spleen extracts and blood serum are devoid of
      it. The spreading power of extracts is destroyed by heating at 60 degrees C. for
      30 minutes, as is also the power to enhance infections. The precise mode of
      action of the Reynals factor is not known, but the results of the experiments
      here presented suggest that it may depend at least in part on the property
      whereby testicle extract increases the spread of injected material and alters the
      permeability of tissue cells. It is not inconceivable that changes in
      permeability facilitate the passage of vaccine virus through the endothelial
      cells of the blood and lymph vessels, and lead to the generalized vaccinia which
      is of frequent occurrence in the reported results (20). It has been shown that
      fluids and suspensions of inert particles are spread by the extract.B. tetanus
      and B. coli exotoxins and trypsin were not enhanced at all in their action
      despite the fact that they were spread through a more extensive area in the
      tissues. Viruses, on the other hand, are markedly influenced and in this respect
      resemble bacteria, not toxins and enzymes. It appears probable that a definite
      capacity for multiplication on the part of an injected substance is required if
      its pathogenic effects are to be enhanced. It may be concluded tentatively that
      the enhancing power of the testicle extract may depend on that property which not
      only spreads the injected material through a larger area but renders the tissue
      cells more easily penetrable by the agents.

PMID- 19869852
TI  - IMMUNIZATION WITH MIXTURES OF POLIOMYELITIS VIRUS AND ALUMINUM HYDROXIDE.
AB  - Preliminary experiments are presented which indicate that poliomyelitis virus can
      be inactivated by a certain preparation of aluminum hydroxide. This effect is
      seen at neutrality and at a pH of 5.5, but not at a pH of 8.8. Monkeys treated by
      repeated subcutaneous injections of poliomyelitis virus so inactivated evince
      immunity as shown by resistance to intranasal instillation and intracerebral
      inoculation as well as by the neutralizing power of their sera. The treatments
      which give rise to the immunity produce no symptoms of disease.

PMID- 19869853
TI  - THE SKIN REACTIONS PRODUCED BY ALTERNATIONS OF HEAT AND X-RAY AT VARIOUS TIME
      INTERVALS.
AB  - Areas on the abdomen of the same guinea pig were exposed to suberythemal doses of
      soft X-rays, to heat of an intensity below the critical dose for the production
      of burns, and to both radiations in sequence with various time intervals between
      the exposures. The only effect of exposure to X-ray or heat alone was a slight
      scaling of the skin. The areas exposed to heat and X-radiation developed well
      marked and persistent burns when the exposure to one agent was made within 3
      hours of the other. Scaling of the skin developed when the exposure to one agent
      was made 1 day after the other. This scaling was more marked and lasted longer
      than the scaling produced by either agent alone. The results were the same no
      matter in which sequence the agents were applied.

PMID- 19869854
TI  - I. EFFECTS OF THE INTRAVENOUS INJECTION OF COLLOIDAL SILVER UPON THE
      HEMATOPOIETIC SYSTEM IN DOGS.
AB  - 1. Colloidal silver has no specific action on the bone marrow in dogs but is a
      systemic poison which may cause anorexia, weakness, loss of weight, anemia, and
      death. 2. Hemolysis can be demonstrated after large doses of colloidal silver and
      the anemia presumably is due in part at least to a destruction of red blood cells
      in the peripheral circulation. 3. The colloidal silver, injected intravenously,
      is deposited as granules almost exclusively in the cells of the reticulo
      endothelial system after the manner of particulate substances. 4. Repeated
      injections of non-lethal amounts of this substance are invariably followed by
      hyperplasia of the bone marrow. In no case was aplasia found. 5. Large single
      doses of this material cause rapid death in 12 hours or less characterized by
      pulmonary edema and congestion. 6. An initial increase in the number of
      erythrocytes and leucocytes may occur following smaller amounts of silver, but
      repeated injections cause a considerable anemia, without a definite increase in
      the leucocytes and with no signs of blood platelet deficiency.

PMID- 19869855
TI  - II. APLASIA OF MARROW AND FATAL INTOXICATION IN DOGS PRODUCED BY ROENTGEN
      RADIATION OF ALL BONES.
AB  - Constant findings were obtained in the acute reaction to the specified amount of
      heavily filtered radiation over the bony skeleton. 1. There develops without
      warning a short and fatal intoxication on the 8th or 9th day after the exposure
      to the radiation. 2. A profound leucopenia appears after 5 to 6 days and is
      maintained in the peripheral blood (200 white blood cells or less per c. mm.) for
      the 2 to 3 days before death. 3. The platelets suddenly disappear from the blood
      smears the day before death. This has some bearing on the life cycle of the
      platelet. 4. All of the organs and body structures present extensive and
      generalized capillary hemorrhage of recent origin. 5. The substance of the spleen
      and lymph nodes is greatly reduced and the germinal centers are visible only as
      remnants. 6. The red cell hematocrit reading drops from about 50 per cent or
      normal to approximately 40 per cent. 7. The bone marrow is depleted of all its
      cells except the connective tissue and fat cells, blood vessel endothelium,
      phagocytes filled with brown granules, and occasional normoblasts.

PMID- 19869856
TI  - III. THE COMBINED EFFECTS OF COLLOIDAL SILVER AND HIGHLY FILTERED ROENTGEN
      RADIATION UPON THE HEMATOPOIETIC SYSTEM IN DOGS.
AB  - 1. The individual destructive effects of colloidal silver and heavily filtered
      radiation are still evident when the two are used together. 2. The combined
      effects are cumulative in that small doses are more destructive than when either
      is used alone. 3. The leucocytosis resulting from the injection of the colloidal
      silver affords no protection against the terminal leucopenia following the
      radiation.

PMID- 19869857
TI  - THE ETIOLOGY OF ACUTE UPPER RESPIRATORY INFECTION (COMMON COLD).
AB  - Experimental upper respiratory infections similar to "common colds" were
      transmitted singly and in series through two and four passages in nine out of
      fifteen persons, by intransal inoculations with bacteria-free filtrates of
      nasopharyngeal washings obtained from individuals ill with natural "colds." These
      observations conform with those reported by previous workers and lend further
      support to the view that the incitant of the "common cold" is a filtrable virus.

PMID- 19869858
TI  - VARIATION AND TYPE SPECIFICITY IN THE BACTERIAL SPECIES HEMOPHILUS INFLUENZAE.
AB  - During the course of a study of different strains of influenza bacilli, fifteen
      strains have been found to form colonies of a different appearance from that
      usually considered typical of influenza bacilli. These colonies are smooth, more
      opaque, and are iridescent in oblique transmitted light. Most of these strains
      were isolated from patients in whom these organisms seemed to play a pathogenic
      ro1e. When these strains were grown repeatedly on blood agar, other colonies
      appeared which were smaller, less smooth, less opaque, and not iridescent, and
      when subcultures were made from these rough colonies, all of the colonies were of
      this character. Further study of the cultures obtained from these smooth and
      rough colonies have shown that one is a variant of the other. The strain from the
      smooth colony has been called an S strain, that from the rough colony an R
      strain. Certain differences in the morphology of the organisms in the R and S
      strains have been observed. Of special importance is the fact that the bacteria
      of the S strains are possessed of capsules. It has also been found that the S
      strains are somewhat more virulent for laboratory animals than are the R strains.
      In the supernatant fluid of broth cultures of S strains, and in the washing fluid
      of S bacteria grown on agar, there is present a soluble substance which, in the
      presence of homologous immune serum, gives rise to a precipitate. No reaction of
      this kind, however, occurs with the cultures of the R strains. By means of cross
      precipitin reactions, employing antisera against the different S strains, it has
      been found that the fifteen strains studied may be divided into two distinct
      immunological groups. Three of these strains belong in one group, Type a, and the
      remaining twelve in another group, Type b. Seven of the strains studied were
      isolated from the spinal fluid in cases of meningitis, and all of these strains
      are of Type b. Agglutination tests performed at 37 degrees C. with these fifteen
      S strains have revealed the same specific type relationships among the organisms
      as did the precipitin tests. The R strains on the other hand, exhibit no similar
      type agglutinations. If the agglutination tests are made at a higher temperature,
      47 degrees C., the S strains also fail to show the specific type reactions which
      occur at 37 degrees C. Certain differences between other biochemical reactions
      exhibited by the two types of strains have been noted, but it is not believed
      that they are sufficiently constant to be of great significance. When S strains
      are grown on artificial media outside the animal body, they tend to be converted
      into the R form. The rapidity and the readiness with which this conversion occurs
      depend on certain conditions, such as the kind of media employed, the temperature
      at which the cultures are kept, and the atmospheric conditions under which they
      are cultivated. The rate of conversion is increased when the S strains are grown
      in media containing anti-S immune serum of the homologous type. On the other
      hand, conversion of R strains into the S form occurs with much less readiness,
      and then only if very particular conditions are present. On one occasion
      conversion occurred when an R strain was grown in a medium containing anti-R
      immune serum. On two other occasions this same strain changed from the R to the S
      form during passage through animals. With other R strains it has so far been
      impossible to bring about this transformation. These studies indicate that the
      bacteria belonging in the group Hemophilus influenzae exhibit changes in
      pathogenicity and immunological specificity, which are analogous to those shown
      by the bacteria of the pneumococcus group. It is important to continue this
      study, with the technique which has been developed, to include a much larger
      number of strains. On account of the readiness with which the S strains of
      influenza bacilli lose their type specificity when grown on artificial culture
      media, it is important that the organisms be studied as soon as possible after
      removal from their pathological sources. It is not impossible that many strains
      lose their specificity immediately after removal from the host, and that the
      specific immunological differentiation of many strains may, for that reason, be
      very difficult, if not impossible.

PMID- 19869859
TI  - STUDIES ON TYPHUS FEVER : VII. ACTIVE IMMUNIZATION AGAINST MEXICAN TYPHUS FEVER
      WITH DEAD VIRUS.
AB  - Guinea pigs can be immunized against Mexican typhus virus by peritoneal
      injections of formalinized Rickettsia material, provided sufficient amounts of
      the organisms are used. Our results in this respect are analogous to those of
      Spencer and Parker with carbolized virus of Rocky Mountain spotted fever. The
      Rickettsia suspensions appear to possess considerable toxicity. We do not wish to
      be misunderstood as implying that the results in guinea pigs offer anything more
      than a demonstration of the principle of active immunization with killed
      Rickettsiae. Application to man will have to be worked out, and preliminary to
      this, we are now attempting to apply the methods to a limited number of monkeys.

PMID- 19869860
TI  - THE INDUCTION OF LYMPHOCYTOSIS AND LYMPHATIC HYPERPLASIA BY MEANS OF PARENTERALLY
      ADMINISTERED PROTEIN.
AB  - Repeated parenteral injections by various routes in a series of twelve rabbits
      caused an increase of lymphocytes in the peripheral blood varying from 23 per
      cent to 139 per cent. It seems probable that the degree of response is
      conditioned upon the type of protein used. At autopsy the lymph nodes and spleen
      showed hyperplastic changes. The thymus did not participate in the hyperplasia.

PMID- 19869861
TI  - EXPERIMENTAL ACUTE GLOMERULITIS.
AB  - 1. Both focal and diffuse glomerulitis has been produced in rabbits by the
      injection directly into the left renal artery of suspensions of heat killed
      hemolytic streptococci. 2. Similar lesions in the glomeruli could not be obtained
      by the injection of suspensions of bismuth oxychloride into the left renal artery
      of normal rabbits. 3. The acute glomerulitis occurred in only about one-half of
      the rabbits employed for the experiments. 4. Glomerulitis was observed much more
      frequently in rabbits in which an acute localized streptococcus infection had
      been produced by the intracutaneous injection of living hemolytic streptococci,
      than in normal rabbits. The occurrence of acute glomerulitis was usually
      associated with a well marked skin reaction to the filtrates of hemolytic
      streptococci.

PMID- 19869862
TI  - STUDIES ON IMMUNOLOGICAL RELATIONSHIPS AMONG THE PNEUMOCOCCI : V. ANAPHYLAXIS AND
      PRECIPITATION BETWEEN ANTIGENS AND ANTISERA OF YEAST OF TYPE II PNEUMOCOCCI.
AB  - This paper reports inter-reactions of anaphylaxis and precipitation between
      antigens and antisera derived from the Type II variety of pneumococcus and from
      one variety of yeast. That the reactions occurred only with Type II and not with
      Types I and III is proof that the pneumococcus antigen responsible for the
      anaphylaxis of the antiyeast sensitized animals was the type-specific
      carbohydrate (S). Pronounced differences in respect to reactivity with the
      pneumococcus antigen were found between individual antiyeast sera that were of
      equal potency in respect to reactivity with the yeast antigen. This fact
      emphasizes the desirability of the use of antisera from a large number of
      individual animals in the study of microbial inter-relationships.

PMID- 19869863
TI  - THE EPIDEMIOLOGY OF PNEUMOCOCCUS INFECTION : THE INCIDENCE AND SPREAD OF
      PNEUMOCOCCI IN THE NASAL PASSAGES AND THROATS OF HEALTHY PERSONS.
AB  - 1. Pneumococci were obtained at one time or another from the nasal passages or
      throats of 80 per cent of 105 adults and children studied. In adults, they were
      obtained more frequently from the throat; in children, as often from the nasal
      passages as from the throat. 2. Of 500 pneumococcus strains studied, 97 per cent
      proved to be serologically specific. They formed smooth colonies and were for the
      most part avirulent for mice. Types I and II were obtained from one and two
      individuals respectively on one occasion only. Type III was obtained from nine
      individuals; Type XIII from nine individuals; Type XVI and Type XVIII from three
      individuals, for varying periods in each case. Atypical pneumococci were secured
      from 13 persons on single and scattered occasions. They varied in colony
      morphology, did not kill mice, or agglutinate in saline, but flocculated in all
      types of antipneumococcus sera employed and over a wide pH range in acid buffers.
      Their occurrence was apparently not associated with any type-transformation or
      virulence-enhancement process in vivo. 3. Strains of pneumococcus obtained on
      successive cultures from a given carrier were, with rare exceptions, of the same
      serological type and were similar in colony morphology, virulence for mice, and
      other tested biological characteristics. 4. Pneumococci of Types I and II were
      obtained under conditions suggestive that they lacked a capacity to spread
      readily; pneumococci of Types III and XIII, on the other hand, were obtained
      under conditions suggestive that they were spreading from person to person. 5.
      The persons studied differed consistently with respect to the occurrence of
      pneumococci. Some were pneumococcus-free, some were transient carriers, some
      periodic, and some chronic carriers. Data are given which suggest that the
      differences were due to variations in host resistance. 6. The incidence of
      pneumococci in all individuals studied underwent a seasonal variation paralleling
      that of coryza and sore throats in the same persons.

PMID- 19869864
TI  - A POTENT ANTIPOLIOMYELITIC HORSE SERUM CONCENTRATE AND ITS EXPERIMENTAL USE IN
      INFECTED MONKEYS.
AB  - 1. The horse, apparently itself unsusceptible to poliomyelitis, can be stimulated
      in certain cases but not all to the production of virucidal antibodies. 2. The
      virucidal potency of such immune serum can be raised to a point comparable to
      that of human convalescent serum and when concentrated and refined exhibits a
      four-fold increase in potency. 3. Such concentrates have proved effective in the
      prevention of paralysis in inoculated monkeys when given intraspinously before
      the onset of paralysis. 4. Treatment has been found more effective when
      therapeutic serums are given through the spinal route. 5. Pooled serum from
      "normal" adult donors has proved effective in neutralizing virus but its potency
      is approximately one-half that of convalescent serum.

PMID- 19869865
TI  - FACTORS INVOLVED IN THE PRODUCTION OF IMMUNITY WITH PNEUMOCOCCUS VACCINE : II.
      INDUCTION OF ACTIVE IMMUNITY DURING THE COURSE OF LOBAR PNEUMONIA.
AB  - 1. Pneumococcus vaccine was administered to 29 patients with pneumonia to
      determine whether a state of immunity could be induced during the course of the
      disease. Twenty patients received an intravenous injection of pneumococcus
      vaccine or pneumococcus filtrate. Nine pneumonia patients received an intradermal
      injection of vaccine. Eight patients with miscellaneous disease received an
      intravenous or intradermal injection of pneumococcus vaccine. 2. Of 23 tests in
      which the serum of the patient was studied for the appearance of protective
      substance after intravenous injection of heterologous pneumococcus vaccine, 20 or
      87 per cent showed a positive response within 6 days after the administration of
      the antigen. The average day of onset was 4.4 days after injection. 3. Of 9 tests
      of the same character following the intravenous injection of pneumococcus
      filtrate, 8 or 89 per cent showed a positive response. The average day of onset
      of protective substance was 5.6 days after injection. 4. The appearance of
      specific protective substance following heterologous injection of pneumococcus
      vaccine appeared to be due to the introduction of the vaccine and not to the
      natural course of the disease, as was shown by negative control experiments. 5.
      Of 24 tests with intradermal injection of vaccine, 10 or 42 per cent developed
      slight protective substance of irregular degree 4.5 days after injection. 6. No
      immediate reactions were observed following the intravenous or intradermal
      injection of pneumococcus vaccine. One chill occurred after injection of
      pneumococcus filtrate. Of 20 cases with intravenous injection of pneumococcus
      vaccine or filtrate, 2 died of their disease, one a case in which homologous
      vaccine was used and one in which heterologous vaccine was administered. 7.
      Conclusions concerning the therapeutic value of the introduction of pneumococcus
      vaccine in pneumonia must await further investigation. These studies demonstrate
      that specific protective substances generally appear 4 to 5 days after
      intravenous injection of pneumococcus vaccine during the course of lobar or
      bronchopneumonia.

PMID- 19869866
TI  - PARATHORMONE DOSAGE AND SERUM CALCIUM AND PHOSPHORUS IN EXPERIMENTAL CHRONIC
      HYPERPARATHYROIDISM LEADING TO OSTITIS FIBROSA.
AB  - 1. On a low calcium intake hypercalcemia tended to disappear in chronic
      hyperparathyroidism on a given dose of parathormone (as large as 6 units per
      kg.), apparently due to the reduction of a readily available calcium reserve. An
      increase of either the calcium intake or of the daily dose of parathormone caused
      a rise of serum calcium and symptoms of overdosage. 2. Hypocalcemia developed in
      chronic hyperparathyroidism in young puppies on a low calcium diet. Tetany
      occurred at a calcium level which was higher and a phosphorus level which was
      lower than in tetania parathyreopriva of young puppies. About 0.1 gm. of calcium
      daily was apparently sufficient to maintain the serum calcium at a normal level.
      3. The serum phosphorus in chronic hyperparathyroidism in young puppies continued
      at or rose above the high level normal for young animals. Toward the end of long
      periods of treatment on large parathormone doses (about 5 units per kg.) serum
      phosphorus approached normal levels, pronounced hypercalcemia was absent but
      hypotonia and other symptoms of hyperparathyroidism were present. 4. A single
      dose of parathormone caused early in the treatment and on liberal calcium intakes
      a more marked relative rise of serum calcium than in normal adult dogs,
      confirming previous observations (5, 8). Later in the treatment and on low
      calcium intakes this effect was greatly reduced. Serum phosphorus rose after a
      single injection of parathormone, even when the effect on the serum calcium was
      slight or absent. 5. The continued effect of parathormone on serum calcium after
      prolonged periods of treatment, and the modified response of the serum phosphorus
      indicate tolerance due to some compensation, rather than immunity. 6. The bone
      lesions, presenting the essential features of ostitis fibrosa cystica (von
      Recklinghausen's disease) in varying degrees of severity, depending on the
      relation of the parathormone dose to the calcium intake and to the duration of
      the treatment, were most prominent on low calcium intakes, which permitted the
      use of large doses of parathormone without fatal hypercalcemia and without
      symptoms of overdosage. 7. Clinical and experimental hyperparathyroidism are
      compared and discussed.

PMID- 19869867
TI  - STUDIES IN THE SEROLOGY OF SYPHILIS : IV. A MORE SENSITIVE ANTIGEN FOR USE IN THE
      WASSERMANN REACTION.
AB  - The discovery (1) that there are many substances with the sensitizing properties
      hitherto believed peculiar to cholesterol and its derivatives, and (2) that
      sensitizer can be added to antigen in very large quantities, many times those
      currently used, and yet continue to increase its complement-fixing efficiency
      with no danger of giving falsely positive tests has made possible the preparation
      of an antigen much more sensitive than any now available for use in the
      Wassermann reaction. 100 gm. of dry powdered beef heart muscle are extracted with
      500 cc. ether for 15 minutes at 37 degrees C. with shaking. After filtration with
      suction, the ether filtrate is discarded. The powder is then dried and extracted
      for 3 to 5 days with 500 cc. of 95 per cent alcohol, with intermittent shaking.
      The mixture is filtered, and the moist powder washed on the filter paper with two
      portions of alcohol, each 100 cc. The alcoholic filtrate and washings are
      combined and evaporated on the steam bath down to 250 to 300 cc. Cholesterol (0.8
      per cent), and sitosterol (0.6 per cent) are then added, and dissolved at 65
      degrees -75 degrees C. The excess sensitizer which crystallizes out upon cooling
      is dissolved just before using by immersing the antigen in a 56 degrees C. bath
      for a few minutes. It is diluted by pouring the saline rapidly into the antigen.
      A 1:40 dilution is recommended for use in water bath fixation ((1/2) hour at 37
      degrees C.), as well as for the short ice box fixation (8 degrees , 4 hours) and
      a 1:120 dilution for use in the overnight ice box method (16 to 24 hours at 8
      degrees C.), as being well beyond its anticomplementary range; the
      anticomplementary quantities being 1:5 and 1:25 respectively. There is reason to
      believe that this antigen possesses almost the maximum sensitivity obtainable.
      The method of preparation insures its being almost saturated with antigen
      lipoids; and more sensitizer could not be added without increasing the turbidity
      of its dilution in saline to a point where it would interfere with the reading of
      hemolysis. Any further improvement must await the discovery of better
      sensitizers. Preliminary experiments indicate that this new sensitizer,
      sitosterol, will find an immediate application, not only in the Wassermann
      reaction, but also in a more sensitive flocculation test to be described in a
      following paper.

PMID- 19869868
TI  - STUDIES IN THE SEROLOGY OF SYPHILIS : V. THE CAUSE OF THE GREATER SENSITIVITY OF
      THE ICE BOX WASSERMANN; THE ZONE PHENOMENON IN COMPLEMENT FIXATION.
AB  - Serum, in concentrations greater than 1:25, causes a marked inhibition of
      complement fixation in general and of the Wassermann reaction in particular. The
      serum protein is probably adsorbed by the colloidally dispersed lipoid-reagin
      complexes, forming a protective film which prevents the fixation (adsorption) of
      complement. This inhibition explains the zone phenomenon in complement fixation:
      a weakly positive serum may give a completely positive reaction in e.g., 1:5
      dilution, and yet, because of this serum inhibition, may appear completely
      negative when tested as whole serum. The greater sensitivity of the ice box test
      is due (1) to the fact that the serum inhibition just described is less marked at
      lower temperature; (2) to the prolonged incubation time, making for greater
      specific fixation; (3) to a more marked non-specific destruction of complement by
      antigen; and (4) a spontaneous deterioration in the longer ice box test. Because
      of the inhibition by serum protein in high concentration, a quantitative
      Wassermann technique involving the use of graded quantities of serum is worthless
      when carried out at 37 degrees C. Even the ice box test, which is less
      susceptible to this inhibiting effect, will yield a positive reaction with whole
      serum only when the circulating reagin exceeds a surprisingly high threshold (six
      to ten times the quantity which could be detected in dilute serum). It is well
      known that a negative Wassermann, even by a very sensitive test, does not exclude
      syphilis: it now appears that a negative Wassermann does not exclude circulating
      reagin.

PMID- 19869869
TI  - SPECIFIC AND NON-SPECIFIC POLYSACCHARIDES OF TYPE IV PNEUMOCOCCUS.
AB  - 1. Three nitrogen-containing polysaccharides have been isolated from autolyzed
      cultures of Type IV pneumococcus: (1) a type-specific carbohydrate differing
      markedly from those of Type I, II, and III pneumococcus, and representing a type
      of substance hitherto not observed among specific polysaccharides, (2) a
      chemically similar carbohydrate without specific function, and (3) the "C"
      substance, or species-specific polysaccharide of Tillett, Goebel, and Avery. 2.
      The chemical differences between the specific polysaccharides of Pneumococcus are
      discussed, and the relationship of the new examples to chitin is pointed out and
      its bearing indicated on the unsettled controversy as to whether or not chitin
      occurs in bacteria. 3. The data of Tillett, Goebel, and Avery on the "C"
      substance have been extended.

PMID- 19869870
TI  - ABSORPTION OF PARTICULATE MATTER BY THE GREAT OMENTUM.
AB  - When the omentum of the dog is floated in a suspension of insoluble nickel
      silicate in physiological saline under circumstances precluding the possibility
      of lymphatic drainage, the liver removed after at least 1 hour contains nickel
      which must have been brought to it by way of the blood capillaries in particulate
      form. The blood capillaries are, therefore, a pathway for absorption of solid
      material but are not important in this respect.

PMID- 19869871
TI  - STUDIES ON INFLAMMATION : VII. FIXATION OF BACTERIA AND OF PARTICULATE MATTER AT
      THE SITE OF INFLAMMATION.
AB  - India ink or graphite partides injected into an area of inflammation fail to
      disseminate to the tributary lymph nodes. When injected into a normal peritoneal
      cavity they rapidly appear in the retrosternal lymph nodes. When injected into an
      inflamed peritoneal cavity they are fixed in situ and fail to reach the regional
      lymph nodes. Graphite particles injected in the circulating blood stream enter an
      inflamed area both as free particles owing to increased capillary permeability
      and also as phagocyted material within leucocytes. Bacteria (B. prodigiosus)
      injected into inflamed tissue are fixed at the site of inflammation and fail to
      disseminate to the regional lymph nodes as readily as when injected into normal
      tissue. Bacteria (B. prodigiosus) injected at the periphery of an inflamed area
      do not readily penetrate into the site of inflammation. The experiments furnish
      evidence, in addition to that already provided, that fixation of foreign
      substances by the inflammatory reaction is primarily due to mechanical
      obstruction caused by a fibrin network and by thrombosed lymphatics at the site
      of inflammation. Bacteria (B. prodigiosus and B. pyocyaneus) injected
      intravenously rapidly enter an inflamed area. It is suggested that localization
      of bacteria in a locus minoris resistentiae may be explained as the result of
      increased capillary permeability with subsequent accumulation and fixation of
      bacteria from the blood stream at the point of injury.

PMID- 19869872
TI  - METABOLISM OF S AND R FORMS OF PNEUMOCOCCUS.
AB  - In the present paper are given the results of studies on the respiratory and
      glycolytic metabolism of Pneumococcus Types I, II, and III, and of the R forms
      derived from these. The metabolism of the S and R forms are compared, and the
      relationship between changes in virulence, changes in chemical constitution, and
      changes in metabolism is discussed. 1. There is no respiration in Ringer solution
      unless sugar is added. 2. The pH (7.8) that is optimal for growth of pneumococcus
      is also the pH at which the maximum respiration occurs. 3. The intensity of
      respiration varies with type in the strains used. The respiratory capacity of
      Type I is 56 per cent of that of Type III, which in turn is 71 per cent of that
      of Type II. 4. The anaerobic glycolysis is approximately the same for all three
      groups. 5. Pneumococcus Type I is capable of aerobic glycolysis. 6. Pneumococcus
      Types II and III do not effect glycolysis aerobically. 7. The energy set free in
      respiration is considerably greater than that set free in glycolysis. 8. The
      oxidation quotient for lactic acid is of the same order as found by Meyerhof in
      muscle and by Warburg for mammalian tissues. 9. The respiratory capacities of
      Types I and III are changed on conversion of the smooth to the rough form. (a)
      For Type I the respiration is increased 110 per cent. (b) For Type III the
      respiration is diminished 45 per cent. (c) For Type II there is only a slight
      diminution in respiratory activity (16 per cent). 10. The anaerobic glycolysis is
      increased about 25 per cent on the average for all R forms irrespective of type
      derivation. 11. Type I on being converted to the R form, loses its capacity for
      aerobic glycolysis. 12. Type III, on being converted to the R form, gains the
      capacity for aerobic glycolysis. 13. The oxygen consumption by Pneumococcus
      compared with that of the human tubercle bacillus and of mammalian tissue, for
      the same time intervals, weight for weight, is as follows: (a) Pneumococcus Type
      I consumes thirteen times as much oxygen as does the tubercle bacillus (H37). (b)
      Pneumococcus Type II consumes thirty-four times as much oxygen as does the
      tubercle bacillus. (c) Pneumococcus Type II consumes over twenty times as much
      oxygen as does isolated rat kidney tissue, and almost 100 times as much oxygen as
      does isolated dog muscle.

PMID- 19869873
TI  - CONGENITAL PROTEIN HYPERSENSITIVENESS IN TWO GENERATIONS.
AB  - Hypersensitivity actively induced in utero is shown to persist for a longer
      period than passive sensitization. The degree of hypersensitivity, its duration,
      and its transmissibility appear to be influenced by the time elapsing between the
      original injection of the parent and parturition. A pregnant guinea pig receiving
      a parenteral injection of antigen 2 to 4 days prior to parturition transmits a
      state of hypersensitivity to two succeeding generations. The sensitization of the
      F(I) generation is due to the passage of antigen. The sensitization of the F(II)
      generation is due to the passage of antibodies formed in the F(I) generation.
      This prevents any further transfer of the hypersensitive state. Though
      hypersensitivity occurs in two successive generations, the phenomenon is
      congenital and not hereditary. We believe that this phenomenon demonstrated in
      the guinea pig is fundamentally related to the problem of congenital
      sensitization of the human being.

PMID- 19869874
TI  - STUDIES ON THE ETIOLOGY OF TRACHOMA.
AB  - A bacillus which corresponds closely with the description of B. granulosis
      Noguchi was isolated from 1 of 5 typical cases of trachoma in Chinese.
      Inoculation of suspensions of this bacillus into the eyelids of M. sinensis
      monkeys produced scarring and contraction of the tarsal cartilages with the
      development of a few conjunctival follicles in 2 out of 5 animals. The possible
      relations of the observed lesions with human trachoma have been discussed.

PMID- 19869875
TI  - STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : VI. BLOOD CELL RELATIONSHIPS IN
      GROUPS OF NORMAL RABBITS WITH RESPECT TO TIME.
AB  - 1. Statistical analyses have been made of the weekly variations in the blood
      counts of groups of normal rabbits to find whether there exists any relationship
      between the numerical changes occurring in the various cell types. Consecutive
      blood counts and differential white cell determinations on five groups of normal
      male rabbits comprising 45 animals in all were made at weekly intervals from
      October, 1927, to June, 1929, the number of observations on each group varying
      from eight to thirty-five. 2. The following relationships between the varying
      group means were found to be consistent and significant:-The number of the red
      blood cells varied with the amount of hemoglobin per cubic millimeter and with
      the number of lymphocytes. There was an inverse relationship between the amount
      of hemoglobin and the number of monocytes. The neutrophiles varied in number with
      the monocytes; the basophiles with the eosinophiles; and the eosinophiles with
      the monocytes. Other associations not always similar but of high significance as
      far as the combined values were concerned, were the relations of the red blood
      cells with the basophiles and the monocytes. The relations of the neutrophiles
      with the red blood cells and the hemoglobin were very irregular. 3. Significant
      association of the white blood cells with variations in the red blood cells and
      the hemoglobin content were observed. The numerical variations in the group means
      of the total white cells were associated with similar variations in the group
      means of the neutrophiles, the lymphocytes, the monocytes, the basophiles, and
      the eosinophiles almost to the degree of their numerical occurrence in the
      peripheral blood. 4. With the exception of the total white cells, approximately
      only half the variations in the group levels of the various cells and of the
      hemoglobin content can be accounted for on the basis of simultaneous associations
      with each other. 5. The red blood cells, the lymphocytes, and the basophiles as
      one group, the eosinophiles and the monocytes as another group, and the
      hemoglobin content and the neutrophiles as a third group, described a definite
      shift from a high to a low numerical value during the 2 year observation period.
      From the standpoint of the magnitude of the shift, the basophiles, the
      eosinophiles, the monocytes, the lymphocytes, and the red blood cells
      participated in the order mentioned. The neutrophiles were only slightly affected
      and the hemoglobin content relatively not at all. 6. No significant relationship
      was ever found, even in the component groups, between the weekly mean values of
      the following: the hemoglobin with the basophiles, the eosinophiles, or the
      lymphocytes; the neutrophiles with the basophiles or the eosinophiles; and the
      lymphocytes with the eosinophiles or the monocytes.

PMID- 19869876
TI  - STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE.
AB  - Lymphoid leucemia of the mouse is readily transmitted by intravenous
      inoculations. The majority of the mice inoculated successfully develop leucemic,
      a smaller number of them, aleucemic lymphadenosis. The data presented favor the
      view that leucemic and aleucemic lymphadenosis are essentially the same
      condition. Leucemia produced by transmission is preceded by an aleucemic stage,
      in which the lymph nodes and the spleen are uniformly enlarged, and the white
      blood count and the percentage of lymphocytes are within the normal range but
      immature lymphocytes are numerous in the circulating blood. Young as well as old
      mice may develop leucemia if leucotic material enters their circulation. Studies
      of transmissible leucemia favor the view that leucemia of mammals is a neoplastic
      disease. The basic problem of leucemia would seem to be determination of the
      factors that bring about a malignant transformation of lymphoid cells.

PMID- 19869877
TI  - A BACTERIOLOGICAL STUDY OF "COLDS" ON AN ISOLATED TROPICAL ISLAND (ST. JOHN,
      UNITED STATES VIRGIN ISLANDS, WEST INDIES.
AB  - Studies in the Virgin Islands, Labrador, and Alabama, suggest that colds are
      incited by some specific agent with which we are not yet familiar. They suggest
      also that the secondary and more severe symptoms associated with colds may be due
      to certain aerobic flora commonly found in the nasopharynx. Types of pneumococci
      which are virulent (to white mice) and true Pfeiffer's bacilli requiring both V
      and X substance (and forming indol?) seem to be of particular importance in these
      secondary infections. The studies indicate that the specific agent which
      initiates colds is infectious in nature, and spread by direct contact, with an
      incubation period of 1 to 3 days. There is strong evidence that environmental
      factors, particularly reduction in atmospheric temperature, have some influence
      upon the incidence of colds.

PMID- 19869878
TI  - THE EFFECT OF SECONDARY INFECTIONS ON EXPERIMENTAL TRACHOMA.
AB  - The possibility suggested itself, in view of the theories already advanced with
      regard to the ro1e of secondary infections in the later manifestations of
      trachoma (1), that the implantation of common bacteria on the conjunctivae of
      monkeys already having well marked characteristic granulosis lesions might give
      rise to a condition showing less predominance of the follicular reaction and more
      of the hyperemic granulopapillary effect. We believe we have succeeded, by a
      suitable technique, in doing this and in producing thereby in the experimental
      animals a condition closely resembling the florid type of human trachoma (Type
      IIb and c of MacCallan). The organisms used were some of those which are found in
      the conjunctival sac of monkey and man with different types of granular
      conjunctivitis. Of themselves, they produced only a transient reaction or none,
      as Noguchi had already shown and as we ourselves had observed in control animals.
      When inoculated together with material containing Bacterium granulosis, they did
      not affect the usual action of this organism, but when introduced into a
      conjunctiva in which granulosis lesions were already well developed, they induced
      more of the characteristics of the florid stage of trachoma than have been
      hitherto observed in animals, notably increased hyperemia, edema and thickening,
      papillary hypertrophy, obscurity of blood vessels, and masking of the follicles.
      Microscopically these changes were accompanied by increased scar tissue
      formation, lymphoid infiltration, and papillary hyperplasia.

PMID- 19869879
TI  - EXPERIMENTAL NEPHRITIS IN THE FROG : II. PERFUSION METHODS OF TESTING THE KIDNEY
      BY DISSOCIATION OF ITS FUNCTIONS.
AB  - 1. A method of testing the frog's kidney by means of perfusion is described. 2.
      This is made possible by dissociating, as far as possible, from the total
      function of the organ the functions of its constituent parts. 3. The
      characteristics by which tubular, glomerular, and combined tubular-glomerular
      lesions may be recognized are described.

PMID- 19869880
TI  - EXPERIMENTAL NEPHRITIS IN THE FROG : III. THE EXTRAVITAL PRODUCTION OF ANATOMICAL
      LESIONS IN THE KIDNEY AND THEIR CORRELATION WITH THE FUNCTIONAL ASPECTS OF
      DAMAGE.
AB  - 1. It is possible to produce in the perfused frog's kidney an experimental
      nephritis which is anatomically similar to that which develops in the living
      animal. 2. The functional effects of these anatomical alterations may be examined
      by a method previously described. 3. The correlation of the two aspects of
      damage, anatomical and functional, is more certain under such conditions than in
      the living animal. 4. The value of the extravital method in general problems is
      indicated by our brief consideration of mitochondrial changes.

PMID- 19869881
TI  - HYPERSENSITIVENESS TO SOLUBLE SPECIFIC SUBSTANCES FROM YEAST-LIKE FUNGI : I.
      ANAPHYLAXIS.
AB  - 1. The polysaccharide fractions from each of five yeast-like fungi produce rapid,
      fatal anaphylactic shock in guinea pigs passively sensitized with antiserum from
      rabbits immunized against the killed organisms. 2. Cross-anaphylactic reactions
      with heterologous polysaccharide fractions are frequent. They parallel closely
      the cross-precipitin reactions, thus adding evidence in favor of the identity of
      precipitin and sensitizing antibody. 3. The polysaccharide fraction from Monilia
      psilosis produces anaphylactic death in guinea pigs actively sensitized with
      killed homologous organisms, but an attempt to sensitize actively with the
      polysaccharide fraction was unsuccessful.

PMID- 19869882
TI  - HYPERSENSITIVENESS TO SOLUBLE SPECIFIC SUBSTANCES FROM YEAST-LIKE FUNGI : II. EYE
      HYPERSENSITIVITY.
AB  - The anterior chamber of the rabbit eye was sensitized by the local injection of
      heat-killed Monilia psilosis. Subsequent intravenous injection of a
      polysaccharide fraction prepared from the same organism elicited a reaction in
      the sensitized eye in five of twelve rabbits.

PMID- 19869883
TI  - THE NEUTRALIZATION OR DESTRUCTION OF DIPHTHERIA TOXIN BY TISSUE.
AB  - As determined by the intracutaneous test in guinea pigs, diphtheria toxin is not
      altered in the presence of cardiac tissue obtained from the fetal or from the
      adult heart of the guinea pig. Tissue cultures were apparently uninjured by the
      presence of the toxin in the dilutions used in these experiments, and, when
      washed with embryo extract after removal of the diluted toxin, continued to grow.
      Embryonic guinea pig cardiac muscle tissue growing in cultures in vitro possesses
      the power of neutralizing, binding, or destroying diphtheria toxin so that it is
      no longer toxic for normal guinea pigs. Such neutralization takes place through
      the intervention of growing tissue and is a property which is lacking in similar
      surviving tissue not in a state of cultivation. Thus, it appears that the living,
      growing cells of the tissues neutralize or destroy limited quantities of toxin;
      only when the quantity of toxin exceeds a certain limit is its action injurious.

PMID- 19869884
TI  - THE INFLUENCE OF X-RAY LESIONS OF THE INTESTINAL MUCOSA ON ABSORPTION OF GLUCOSE
      AND OTHER SUGARS.
AB  - A sublethal dose of x-rays was applied over the abdomen of rats and over the
      thorax for control purposes. 20 and 40 hours after radiation (i.e. during the
      "latent period") the rate of absorption of glucose, fructose and mannose was
      markedly diminished. Simultaneously definite histological changes were observed
      in the intestinal mucosa. In spite of the decrease in the absolute amount
      absorbed, the relative rate of absorption of the three sugars mentioned remained
      nearly unchanged, indicating that the epithelial cells retained their selective
      action on sugars.

PMID- 19869885
TI  - THE ETIOLOGY OF INFECTIOUS DIARRHEA (WINTER SCOURS) IN CATTLE.
AB  - A disease of cows manifested by severe diarrhea has been described. The condition
      is characterized by the frequent passage of dark brown or black feces, often
      containing mucus and blood. The principal lesions are catarrhal inflammation of
      the small intestine and liver degeneration. By feeding feces from spontaneous
      cases to calves a similar but milder disease characterized by the same type of
      enteritis was produced. Vibrios were cultivated from the inflamed intestinal
      tract of such experimentally induced cases. Pure cultures of the vibrios when fed
      to other calves, in certain instances, produced diarrhea and a well marked
      enteritis similar to that observed in both the spontaneous disease and in calves
      following the feeding of feces from naturally affected cows. Vibrios were
      recovered from the inflamed small intestine of three out of four animals fed such
      cultures.

PMID- 19869886
TI  - VIBRIONIC ENTERITIS IN CALVES.
AB  - An intestinal disorder of calves has been described. The clinical manifestations
      are usually observed in calves 2 or more weeks old. Our experiments indicate that
      infection may take place relatively early in life and may for a time produce only
      a mild reaction, but as the disease becomes more chronic the clinical
      manifestations become more pronounced. The anterior portion of the jejunum is the
      primary locus of infection but in more chronic cases practically the whole small
      intestine may be involved. Vibrios were cultivated from the inflamed intestinal
      mucosa in both the acute and more chronic spontaneous cases. Vibrios were also
      obtained from the acutely involved intestine of young calves experimentally
      exposed to natural infection. On three occasions similar vibrios were found in
      cultures from the liver. When a single strain of vibrios which had been under
      cultivation for 3 months was fed to a young calf subclinical infection was
      produced and the organism recovered. This strain after three passages on media
      when fed to a calf produced a severe inflammation of the jejunum and ileum and
      from these areas the organism was recovered.

PMID- 19869887
TI  - VIBRIOS (VIBRIO JEJUNI, N.SP.) ASSOCIATED WITH INTESTINAL DISORDERS OF COWS AND
      CALVES.
AB  - A number of vibrios obtained from the small intestines of calves fed feces from
      spontaneous diarrhea in cows, natural intestinal disorders of calves,
      experimentally induced infections of calves, and cultures obtained from Dr.
      Theobald Smith have been studied. From the close morphological resemblance,
      similarities in motility, position and number of flagella, tinctorial properties,
      and the tendency to fragmentation in older cultures, as well as the narrow
      nutritive requirements, we are led to regard them as a closely allied group and
      we propose the name Vibrio jejuni. Immunologically as judged by agglutination the
      organisms have been divided into two groups, the smaller representing two strains
      originating from diarrhea in cows and the larger comprising one from this source
      and many from the calf disease. The larger group can be subdivided by means of
      agglutination absorption into cultures which do not contain the complete
      antigenic complex and others which do so. Certain freshly isolated vibrios when
      injected into rabbits incite definite reactions terminating in a localization in
      the small intestine accompanied by catarrhal inflammation.

PMID- 19869888
TI  - CHEMICAL CHANGES IN THE BLOOD OF THE DOG IN EXPERIMENTAL BILE PERITONITIS.
AB  - 1. Changes in the chemistry of the blood of dogs with experimental bile
      peritonitis are here reported. 2. In all animals that died, a bile ascites was
      found. 3. Dogs dying of bile peritonitis showed a constant increase in the blood
      non-protein and urea nitrogen, and a fall in the chlorides.

PMID- 19869889
TI  - STUDIES ON BARTONELLA MURIS ANEMIA : IV. PATHOLOGICAL CHANGES DURING THE ACUTE
      ANEMIA.
AB  - The pathological changes that follow a severe infection with Bartonella muris in
      the adult or young albino rat are: First, those that result from the release of
      large quantities of cellular debris in the circulating blood. There is phagocytic
      activity and hyperplasia of the endothelial elements of the liver, thymus, lymph
      nodes and, in the young rat, of these elements in the spleen, with resultant
      capillary thromboses and focal necroses. Second, changes result from the anemia
      as such-fatty metamorphosis of heart, liver and kidneys. Third, there is a severe
      nephrosis and in some instances a degenerative process in the glomeruli. In the
      bone marrow hyperplasia of erythropoietic elements occurs.

PMID- 19869890
TI  - STUDIES ON BARTONELLA MURIS ANEMIA : V. COMPENSATORY PHENOMENA FOLLOWING
      SPLENECTOMY IN THE ADULT ALBINO RAT.
AB  - In Bartonella muris carrier stock certain changes are observed in the
      lymphoblastic and reticular and endothelial elements after splenectomy and
      recovery from the anemia. These changes appear 3 to 5 months after splenectomy
      and are associated with immunity to further infection with Bartonella muris. The
      changes consist primarily of hyperplasia of hemolymph tissue, hyperplasia of
      reticular and endothelial elements of lymph nodes, the formation of lymphoblastic
      foci periportally in the liver and peribronchially and perivascularly in the
      lung, regeneration of all elements of the thymus and marked hyperplasia of all
      elements of the bone marrow (increased hematopoiesis).

PMID- 19869891
TI  - ACTIVE IMMUNIZATION AGAINST POLIOMYELITIS IN MONKEYS.
AB  - 1. A combination of poliomyelitis virus and specific human serum is effective for
      the production of active immunity. 2. For each gram of active virus given
      intradermally as an emulsion, 6 cc. of human immune serum, injected
      subcutaneously, was required in our experiments to protect a monkey from
      paralysis. Some degree of active immunity was induced. 3. Immunity, without
      symptom of the disease, was secured when the serum was given at the time of
      inoculation, or within 3 days preceding or following inoculation of the virus. 4.
      For the production of immunity, virus, preceded by serum administration, is
      probably less effective than when it is given simultaneously with, or before, the
      injection of serum. 5. The virus neutralization test is more sensitive than the
      direct intracerebral test for determining the production of immunity.

PMID- 19869892
TI  - STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : VII. OBSERVATIONS ON RABBITS
      INOCULATED WITH A TRANSPLANTABLE MALIGNANT NEOPLASM.
AB  - Successive blood counts at weekly intervals were made on rabbits inoculated with
      a transplantable malignant neoplasm of epithelial origin. There were 78 animals
      distributed in 9 groups; the period of observation after inoculation was 2
      months. The results have been considered with respect to the character of the
      tumor process as determined by postmortem examination, the animals being
      classified as deaths, probable deaths, probable recoveries, and recoveries. The
      blood findings have been analyzed on the basis of the values derived from normal
      rabbits. A comparison has also been made with the results of preinoculation
      counts. In rabbits in which the tumor process was of pronounced or well marked
      severity, the numbers of monocytes became greatly increased; the neutrophiles and
      the total white blood cells were also increased; the eosinophiles, and to a less
      extent, the basophiles and lymphocytes were decreased; the red cell count was
      decreased and the hemoglobin content was lowered. In rabbits which recovered from
      the tumor inoculation, there were no outstanding changes in the blood picture
      when the findings for the entire observation period were considered. In the group
      of probable recoveries, the results were variable; there was, however, a definite
      although moderate increase of monocytes, and in general, the findings reflected
      the mildness of the disease when compared with those of the fatal cases and the
      group of probable deaths.

PMID- 19869893
TI  - THE ACCUMULATION OF IRON IN TUBERCULOUS AREAS.
AB  - Repeated daily intravenous injections of ferric chloride solution are followed by
      an accumulation of iron in tuberculous areas of lungs. The iron accumulates in
      the caseous areas of tubercles and is demonstrable by the Prussian blue reaction.
      Quantitative determinations corroborate these results and show that the iron
      content of lung tissue in tuberculous animals injected with ferric chloride
      exceeds that in normal animals injected with this salt, as well as that in non
      injected tuberculous animals.

PMID- 19869894
TI  - PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: PASSIVE IMMUNITY TO
      REACTING FACTORS.
AB  - It has proved possible to elicit passive immunity to B. typhosus reacting factors
      by means of normal and immune homologous neutralizing antibodies. The in vivo
      serum protection against these factors followed the law of multiple proportions.
      There was observed a considerable loss of antibodies from the blood stream.
      Passive immunity was best obtained when the immune serum was injected
      intravenously (1/2) hour before the intravenous injection of the reacting
      factors. It was possible to prevent the occurrence of the local skin reaction by
      an intravenous injection of serum after the intravenous injection of the reacting
      factors, provided the serum dose was very large and provided the serum injection
      was made immediately after the filtrate injection. A number of experiments
      clearly demonstrated the interesting fact that the greater the amount of
      antiserum injected intravenously, the more efficient was the in vivo
      neutralization, in a ratio distinctly greater than the quantitative increase of
      serum. It is suggested that there may be a practical value of the observation in
      relation to serum therapy. The results also demonstrated passive serum protection
      against the lethal effect of B. typhosus "agar washings" filtrates, in a ratio
      which seemed to suggest the law of multiple proportions.

PMID- 19869895
TI  - PSITTACOSIS : II. EXPERIMENTALLY INDUCED INFECTIONS IN MICE.
AB  - The work presented in this communication concerning psittacosis in mice confirms
      Krumwiede's observations that mice inoculated intraperitoneally with emulsified
      livers and spleens containing the virus develop the disease and that the malady
      can in this way be passed serially through a number of mice. Furthermore, it has
      been shown that mice are susceptible to the virus administered intracerebrally
      and that the active agent can be propagated indefinitely by means of brain to
      brain inoculations. Moreover, by the use of mice, the presence of the virus of
      psittacosis in the sputum of a patient with the disease has for the first time
      been demonstrated. It follows that the mouse is available for diagnostic
      purposes. The pathological findings in infected mice consist of enlarged fatty
      livers that frequently show areas of necrosis infiltrated with polymorphonuclear
      and mononuclear cells; enlarged spleens with areas of necrosis and cellular
      infiltrations involving the pulp and lymphoid follicles; and, finally, in
      intracerebrally infected animals, a meningoencephalitis. The "minute bodies"
      described by other observers were not found in all animals, but they were seen
      with sufficient frequency in smears of peritoneal and meningeal exudates and in
      smears and sections of livers and spleens to demand serious consideration as the
      possible etiological agent of the disease. Neutralizing and protective antibodies
      were not found in convalescent human sera when the mouse was used as the test
      animal.

PMID- 19869896
TI  - STUDIES ON TYPHUS FEVER : VIII. TICKS AS A POSSIBLE VECTOR OF THE DISEASE FROM
      ANIMALS TO MAN.
AB  - Mexican typhus virus can be passed through ticks by the method of rectal
      injection. The virus will remain alive in the ticks for at least 12 days. These
      studies, together with one of our preceding publications and the work of Dyer,
      demonstrate that there are at least three insects-bedbugs, fleas and ticks-which
      must be considered as possibilities in conveying typhus fever from an animal
      reservoir to man. Our work will be continued by a study of rats and mice caught
      in typhus regions such as Mexico City and its immediate vicinity, with a search
      for the virus in these rodents as well as an analysis of the insects found upon
      them or in the localities in which they are concentrated.

PMID- 19869897
TI  - PSITTACOSIS : III. EXPERIMENTALLY INDUCED INFECTIONS IN RABBITS AND GUINEA PIGS.
AB  - 1. Rabbits and guinea pigs are susceptible to psittacosis virus introduced
      intracerebrally. By means of brain to brain passages in these animals the active
      agent is capable of propagation indefinitely. 2. Serial passages of the virus
      through rabbits and guinea pigs do not cause the active agent to lose its
      pathogenicity for parrots and mice. 3. The chief clinical evidences of infection
      in rabbits and guinea pigs following intracranial inoculation of the virus are
      fever and loss of weight. The pathological changes are characterized by a mild
      meningo-encephalitis, and fatty degeneration, focal necrosis, and infarction of
      the liver. 4. Rabbits upon recovery from an attack of psittacosis are actively
      immune. 5. Two strains of virus, human and parrot, were found to be
      immunologically similar. 6. No evidence was obtained to show that human
      convalescent serum possesses an appreciable amount of neutralizing substances.

PMID- 19869898
TI  - PSITTACOSIS : IV. EXPERIMENTALLY INDUCED INFECTIONS IN MONKEYS.
AB  - The virus of psittacosis inoculated intratracheally or intranasally in monkeys
      produces a pneumonia similar to that caused by the same active agent in man.
      Intracerebral inoculation of the virus induces a meningo-encephalitis
      characterized principally by a mononuclear reaction in the meninges. Indirect
      evidence has been adduced to show that the portal of entry of the virus in man is
      the upper respiratory tract.

PMID- 19869899
TI  - EXPERIMENTAL HYPERTHYROIDISM AND ITS EFFECT UPON THE MYOCARDIUM IN GUINEA PIGS
      AND RABBITS.
AB  - A study has been made of the pathological changes in the hearts and other tissues
      of animals rendered hyperthyroid with thyroxine. Forty-four rabbits and seventeen
      guinea pigs were given intramuscular injections of thyroxine every other day and
      sacrificed at varying intervals. Tissues from a series of normal animals (twenty
      guinea pigs and forty-three rabbits) were examined as a control. The changes in
      the heart and other tissues of hyperthyroid animals were insignificant and varied
      but little from changes seen in normal control animals. Of eight thyrotoxic
      guinea pigs that developed coincidental infection (bronchisepticus) all showed
      myocardial lesions. Of nine thyrotoxic guinea pigs, free of infection, only one
      gave evidence of myocardial change. It is pointed out that hyperthyroidism, per
      se, cannot be held responsible for these lesions, which would appear to have been
      associated with the infection. It was noted that rigor mortis of the skeletal
      muscles occurred much sooner in the bodies of hyperthyroid animals than in normal
      animals.

PMID- 19869900
TI  - TRANSMISSION AND CULTIVATION EXPERIMENTS WITH HUMAN TRACHOMA AND THE EXPERIMENTAL
      DISEASE IN MONKEYS.
AB  - 1. Conjunctival tissue derived from alien and native American white persons in
      New York City, having trachoma in an advanced stage, has been used successfully
      to induce in Macacus rhesus monkeys characteristic granular conjunctivitis. The
      transfer of infection was effected either by a single subconjunctival injection,
      or by repeated swabbing with conjunctival secretions. 2. Pathogenic strains of
      Bacterium granulosis have been recovered from the trachomatous tissues of six out
      of eleven patients. In addition, the organisms have been isolated from the
      monkeys infected with human material. 3. Repeated swabbing with secretions
      obtained from monkeys having experimental trachoma has given rise to
      characteristic granular conjunctivitis in normal animals. In addition, repeated
      instillations of suspensions of conjunctival tissue fragments derived from
      affected monkeys have led to characteristic infection of the conjunctivae of
      normal monkeys. 4. Contact infection occurs in monkeys, as it has long been known
      to occur in human beings; animals with smooth conjunctivae developing the
      experimental disease when merely caged with infected monkeys. 5. Repeated
      instillation of cultures followed by rubbing the eyelids will lead to the disease
      in monkeys, a method of transfer which indicates one manner in which the
      affection may be transmitted from man to man. Yet another manner of producing the
      experimental condition is by repeated swabbing with cultures of Bacterium
      granulosis. Noguchi has already reported the successful outcome of the
      subconjunctival inoculation of cultures and the spread of the disease from an
      infected conjunctiva to the other eye of the same animal. 6. Tissues derived from
      cases of human trachoma or from monkeys having the experimental disease induce,
      on conjunctival inoculation of Macacus rhesus monkeys, the same clinical and
      pathological effects as do cultures of Bacterium granulosis. The conjunctival
      lesions closely resemble, in clinical appearance and in microscopic changes,
      those of the follicular stages of trachoma in man.

PMID- 19869901
TI  - THE PATHOLOGY OF EXPERIMENTAL DERMAL PNEUMOCOCCUS INFECTION IN THE RABBIT.
AB  - 1. The pathology of the experimental dermal pneumococcic infection in the rabbit
      is described in detail and the findings are compared with the histological
      alterations seen in the human pneumonic lung. There would appear to be a basic
      similarity of the lesions in both tissues. 2. A copious production of edema fluid
      is the outstanding characteristic of the early lesion. It occurs prior to any
      significant cellular change. In the spreading lesion an infiltration of the
      tissues with fluid precedes any other sign of reaction between tissue and
      microorganism. It seems likely that the advancing fluid carries with it the
      infecting organisms and inoculates all tissues which it reaches. The resulting
      infection seems not to take place by an active invasion of microorganisms but by
      a progressive inoculation from an infected fluid.

PMID- 19869902
TI  - DECOMPOSITION OF THE CAPSULAR POLYSACCHARIDE OF PNEUMOCOCCUS TYPE III BY A
      BACTERIAL ENZYME.
AB  - 1. An organism has been isolated from peat soil which decomposes the specific
      capsular polysaccharide of Type III Pneumococcus. 2. The isolation has been made
      possible by the use of a synthetic mineral medium containing the specific
      polysaccharide as sole source of carbon. By repeated transfers in this medium the
      potential capacity of the organism to decompose the specific substance has been
      progressively increased. 3. The organism is a pleomorphic bacillus, motile and
      spore-bearing, exhibiting metachromatic granules; its reaction to the Gram stain
      varies according to the medium on which it is grown. It is strictly aerobic and
      grows well in plain broth and peptone solutions; it does not produce gas in any
      media and it forms small amounts of acid only on dextrin, galactose, lactose,
      salicin, and trehalose; its growth is inhibited by glucose. 4. The organism
      decomposes the capsular polysaccharide of Type III Pneumococcus aerobically,
      between pH 6.2 and 7.8, at room temperature and at 37.5 degrees C., but not at 54
      degrees C. The decomposition of the specific substance is inhibited by the
      presence in the medium of other nutrients, such as peptones, which act as a more
      readily available source of energy. The action of the organism is specific; it
      does not attack the soluble specific substance of Type I or Type II Pneumococcus,
      nor any of the other bacterial polysaccharides thus far tested. 5. The organism
      possesses an endocellular enzyme. This enzyme has been extracted by autolysis of
      the bacterial cells; in sterile solution it exhibits the same specific action as
      do the organisms from which it is derived, decomposing only the capsular
      polysaccharide of Type III Pneumococcus. 6. This enzyme decomposes the Type III
      specific polysaccharide under anaerobic as well as under aerobic conditions; it
      is inactivated at 60-65 degrees C.; the rate of decomposition of the specific
      substance is not affected by the presence of normal serum. 7. There exists a
      quantitative relationship between the total amount of specific substance
      decomposed and the amount of enzyme preparation used; the existence of this
      relation makes it possible to express the activity of a given enzyme preparation
      in terms of the minimal amount required for the complete decomposition of a given
      amount of specific substance. 8. The specific decomposition of the capsular
      polysaccharide of Type III Pneumococcus, by the organism as well as by the enzyme
      it produces, illustrates once more the specificity of the types of Pneumococcus
      and confirms the fact that the capsular polysaccharides, and not some impurities
      carried along with them, are responsible for type specificity.

PMID- 19869903
TI  - THE PROTECTIVE ACTION OF A SPECIFIC ENZYME AGAINST TYPE III PNEUMOCOCCUS
      INFECTION IN MICE.
AB  - The bacterial enzyme which decomposes the purified capsular polysaccharide of
      Type III Pneumococcus in vitro also destroys the capsules of the living organisms
      growing in media and in the animal body. Potent preparations of this same enzyme
      protect mice against infection with virulent Type III Pneumococcus. The
      protective action is type-specific. The protective activity of the specific
      enzyme is destroyed by heat (70 degrees C. for 10 minutes). The enzyme remains in
      an effective concentration 24 to 48 hours after its injection into normal mice.
      The enzyme has been found to exert a favorable influence on the outcome of an
      infection already established at the time of treatment. A definite relationship
      has been found to exist between the activity of the enzyme in vitro and its
      protective power in the animal body. The mechanism of the protective action is
      discussed with special reference to the relation between the decapsulation of the
      bacteria by the enzyme and the phagocytic response of the host.

PMID- 19869904
TI  - PSITTACOSIS : I. EXPERIMENTALLY INDUCED INFECTIONS IN PARROTS.
AB  - 1. The virus of psittacosis is present in the nasal secretions, feces, blood,
      spleen, and liver of an infected parrot. 2. Parrots are susceptible to intraoral,
      intranasal, or intramuscular inoculations of the virus. 3. The most constant
      pathological changes produced by psittacosis in parrots occur in the spleen and
      liver. The lesions exhibited in the latter organ consist of areas of necrotic
      liver cells and damage to bile ducts. In no instance, in our experience, were
      lesions observed in a parrot's lungs comparable to those found in the lungs of
      men. 4. "Minute bodies" similar to those described by Levinthal and others were
      found in many, but not in all of the infected birds. 5. Parrots that have
      recovered from one attack of psittacosis exhibit an active immunity against
      reinfection.

PMID- 19869905
TI  - NUTRITIONAL MUSCULAR DYSTROPHY IN THE GUINEA PIG AND RABBIT.
AB  - A diet is described, which leads to a progressive, highly selective, and
      ultimately fatal dystrophy of the voluntary muscles. Guinea pigs and rabbits are
      susceptible, rats resistant. The diet used is complete in known requirements,
      except for vitamin E; the addition of this factor, however, does not prevent the
      development of the disease. The lesions are not due to inanition, infection, or
      scurvy, and must be referred to some still unknown factor.

PMID- 19869906
TI  - NERVE ENDINGS IN NUTRITIONAL MUSCULAR DYSTROPHY IN GUINEA PIGS.
AB  - The nutritional muscle dystrophy of guinea pigs and rabbits is primarily a
      degeneration of the muscle fibers and is not associated with visible alterations
      of the peripheral nerves or their motor terminals.

PMID- 19869907
TI  - REACTION OF YOUNG AND ADULT RABBITS TO PNEUMOCOCCI INJECTED INTO THE SKIN.
AB  - 1. Young and adult rabbits react differently to intracutaneous injection of
      virulent pneumococci. In adult rabbits a very extensive inflammation develops at
      the site of infection and bacteriemia and death occur only in a relatively few
      rabbits. Young rabbits fail to develop extensive inflammation and die with
      bacteriemia. 2. It is probable that the fate of the animals is influenced by the
      capacity to develop inflammation at the site of injection of pneumococci.

PMID- 19869908
TI  - TYPHUS FEVER : I. COMPARATIVE STUDY OF EUROPEAN AND AMERICAN TYPHUS IN LABORATORY
      ANIMALS.
AB  - Study of two strains of epidemic (European) typhus and two strains of endemic
      (American) typhus in laboratory animals has shown their essential identity. .The
      characteristic typhus brain lesions can be shown to occur in all four strains
      after subcutaneous inoculation and Rickettsiae-filled cells can be found in the
      scrotal sac in all four strains after intraperitoneal inoculations. A strain of
      European typhus, which for 8 years has yielded no obvious scrotal reaction in
      guinea pigs, afterwards gave rise to a periodic scrotal reaction of variable
      severity. At present it occupies an intermediate position in this respect between
      the recently isolated European strain and the American strains. Variations in the
      scrotal reaction in guinea pigs appear to be correlated with strain variations in
      virulence in the human host. The incubation period in guinea pigs after
      intraperitoneal inoculation depends largely on the number of Rickettsiae
      injected.

PMID- 19869909
TI  - TYPHUS FEVER : II. CYTOLOGICAL STUDIES OF THE SCROTAL SAC EXUDATE IN TYPHUS
      INFECTED GUINEA PIGS.
AB  - 1. A satisfactory method is described for the topographical study of Rickettsia
      prowazeki in sections of the scrotal sac of typhus-infected guinea pigs. 2. In
      such sections Rickettsiae are always intracellular. 3. Typhus Rickettsiae
      multiply luxuriantly in the serosal cells and produce great distention of these
      cells. 4. Rickettsiae may be found in small numbers in the endothelial cells
      lining the underlying capillaries in the testes and scrotum, but are not seen in
      perivascular macrophages, connective tissue cells, fat cells, smooth or striated
      muscle fibres or epithelial cells. 5. Rickettsiae are rarely phagocytosed in
      small numbers by polymorphonuclears but are never seen in lymphocytes, plasma
      cells or eosinophiles. 6. When infected mesothelial cells proliferate and
      desquamate, they rapidly lose their content of Rickettsiae. 7. The large
      mononuclear cells seen in smears of the scrotal sac exudate may be separated into
      two groups: (1) the serosal (mesothelial) cells which become heavily infected
      with Rickettsiae but which are not phagocytic for graphite ink and (2) the
      macrophages (phagocytic cells) which do not contain Rickettsiae.

PMID- 19869910
TI  - THE EFFECT OF TESTICLE EXTRACT ON RED BLOOD CELLS IN VITRO.
AB  - Testicle extract possesses a notable power to increase red cell fragility.
      Testicle extracts of the rat, rabbit and guinea pig all exhibit this property,
      which is most pronounced with the extract from the rat and least so with that
      from the guinea pig. Splenic extract does not possess the property, or possesses
      it only to a very slight degree. These results support the hypothesis that the
      factor in testicle extract which enhances infections (the Reynals factor) does so
      by altering the permeability of the host tissue.

PMID- 19869911
TI  - PYOCYANINE, AN ACCESSORY RESPIRATORY ENZYME.
AB  - Pyocyanine, the blue pigment of B. pyocyaneus, can increase the respiration of
      living cells to a great degree (maximum observed increase 24-fold). The
      reversibility of its oxidation and reduction is responsible for this. The effect
      is non-species-specific and has been observed in varying degrees with B.
      pyocyaneus, Staphylococcus aureus, Pneumococcus Type III, and the red blood
      corpuscles of rabbits. The effect of pyocyanine is dependent on the presence of
      another respiratory ferment sensitive to potassium cyanide and carbon monoxide.
      The increase of respiration induced by pyocyanine is paralleled by an increase in
      the respiratory quotient. The pyocyanine catalysis is not indiscriminately
      effective in all oxidations, but only in the oxidation of certain substances
      closely associated with the bacterial body.

PMID- 19869912
TI  - BLOOD CHEMICAL CHANGES IN EXPERIMENTAL STREPTOCOCCUS SEPTICEMIA.
AB  - The following changes have been found to occur in rabbits given fatal intravenous
      doses of Streptococcus hemolyticus: The blood sugar concentration drops at a
      constant rate throughout the disease, but does not reach a condition of
      hypoglycemia. Glycogen is present in the liver at death. The CO(2) capacity is
      lowered markedly at first, then returns to a somewhat higher level, at which it
      continues until the terminal stage of the disease, when the acidosis becomes very
      marked. Inorganic phosphorus is markedly increased in concentration at the
      terminus of the disease. This increase is greater in animals showing an acute
      course than in those in which the disease is of the fulminating type. Calcium
      also shows terminal changes, decreases occurring in both groups. In the acutely
      infected rabbits the decrease is less than in the fulminating group, although in
      both a pathological level is reached. Non-protein nitrogen and creatinine are
      greatly increased in the terminal stages, in both groups of animals. It is
      suggested that these observations can be explained on the assumption of a large
      amount of acid production by the streptococcus in vivo.

PMID- 19869913
TI  - AN EXPERIMENTAL STUDY OF "MAD ITCH" WITH ESPECIAL REFERENCE TO ITS RELATIONSHIP
      TO PSEUDORABIES.
AB  - The clinical picture and gross pathology of spontaneous and experimental "mad
      itch" have been described and the inciting agent has been shown to be a filtrable
      virus. It has been possible to prepare virucidal serum capable of neutralizing
      the virus. Fatal infections are regularly produced in rabbits when the virus is
      administered subcutaneously, intracerebrally, intravenously, intratesticularly,
      intraperitoneally, intranasally, or when it is dropped on a scarified area of
      skin. Its infectivity for other species by various routes is reported upon. The
      rabbit, guinea pig, white rat, white mouse, gray field mouse, cow, cat, duck,
      chicken, and hog are susceptible to experimental infection. The disease is not
      contagious under laboratory conditions and the virus is restricted in the animal
      body largely to the region of inoculation and the lung. The virus can be stored
      for relatively long periods in 50 per cent glycerol or in the dried state. A
      comparison of "mad itch" with pseudorabies leads to the tentative conclusion that
      the inciting agents of both are the same, although the strains of the two viruses
      that are under study possess readily demonstrable differences.

PMID- 19869914
TI  - LOCAL ORGAN HYPERSENSITIVENESS : III. FURTHER OBSERVATIONS ON ITS EXPERIMENTAL
      PRODUCTION IN THE RABBIT EYE.
AB  - 1. Rabbit eyes sensitized with guinea pig red blood cells or fresh egg white
      respond with an inflammatory reaction following the intravenous injection of the
      homologous antigen, but not the heterologous. 2. Two-tenths of 1.0 cc. of a
      multiple antigen containing ten separate ingredients, or in other words, 0.02 cc.
      of each foreign protein, when introduced into the rabbit's anterior chamber, is
      sufficient to produce an altered ocular reactivity such that when 1 cc. of one of
      the ten antigens is introduced intravenously the eye shows hyperemia of the iris
      and conjunctiva with more or less edema and lacrimation during the next 24 hours.
      3. For as long as 8 months after sensitization eyes will respond with an
      inflammatory reaction following the intravenous injection of fractions of the
      total antigen. 4. Repeated daily intravenous injections of a single antigen
      usually produce no reaction in the sensitized eye after the first few days.
      Injection of different antigens intravenously on succeeding days produces a
      continued sterile inflammatory process in the sensitized eye. After the total
      number of single antigens has been injected, repetition of these injections now
      fails to produce a similar response. Instead, the eye reaction is at a much lower
      level and the inflammatory response is manifested only to a few of the antigens
      injected intravenously. 5. Unless massive doses of antigen are used to
      desensitize, permanent desensitization of the eye has not occurred in animals
      which have been followed for at least 8 months. Animals may develop maximal eye
      responses following repeated intravenous injections of the same antigen, if
      sufficient time has elapsed between injections. Nevertheless, the eye reactions
      which can be elicited 6 or 7 months after sensitization are less intense than the
      initial responses. 6. The ability of the eye inflammation to light up following
      the intravenous injection of homologous antigen is not due to an initial tissue
      injury as proven by the fact that the reaction is specific and anterior chambers
      injured with typhoid vaccine, iodine, saline, glycerine, or albolene will not
      respond subsequently when the various proteins used for sensitization of the
      other eyes are injected intravenously. 7. It has been impossible to demonstrate
      sensitivity in the eye by the intravenous shocking route until at least the 5th
      day following introduction of the antigen into the anterior chamber. 8. The eye
      reaction can be produced by the subcutaneous as well as the intravenous injection
      of antigen. 9. Rabbits vary considerably in the intensity of the eye reaction
      which can be elicited in them, but only rarely was an animal found which failed
      completely to give a reaction.

PMID- 19869915
TI  - LOCAL ORGAN HYPERSENSITIVENESS : IV. INFLAMMATION PRODUCED IN THE ACTIVELY
      SENSITIZED RABBIT EYE BY THE INTRODUCTION OF HOMOLOGOUS ANTIGEN INTO THE
      GASTROINTESTINAL TRACT.
AB  - In the actively sensitized rabbit eye a sterile inflammation may develop after
      the introduction of the homologous antigen into the gastrointestinal tract.

PMID- 19869916
TI  - CRITERIA OF THE AGE OF LYMPHOCYTES IN THE PERIPHERAL BLOOD.
AB  - The study of blood from rabbits with normal and with hyperactive lymphatic tissue
      reveals, in the latter, a greater percentage of lymphocytes with heavily
      basophilic cytoplasm and numerous mitochondria. This indicates that cytoplasmic
      basophilia and mitochondrial content can serve as criteria of the degree of
      maturity of the lymphocyte, these characters having the same significance in this
      relation as obtains with other blood cells. Basophilia is the more evident and
      reliable indicator of youth of the cells. The classification of lymphocytes into
      three groups, according to degree of basophilia, has yielded figures which show
      the proportions of the three to be relatively stable in blood from normal adult
      human beings and rabbits. Size is not strictly a function of age in lymphocytes.
      Moreover, there is no correspondence in the size of lymphocytes in supravital
      films and in fixed specimens obtained by the "cover glass" method. There is a
      change of size during fixation. Although lymphocytes of intermediate and large
      size may be of any age, in supravital preparations the majority are young cells,
      whereas in fixed films the reverse obtains. The small lymphocyte may be of any
      age in specimens examined by either technique. The total number of lymphocytes
      circulating at any given time is not necessarily an index to lymphoid activity.

PMID- 19869917
TI  - ON THE SPECIFICITY OF SEROLOGICAL REACTIONS WITH SIMPLE CHEMICAL COMPOUNDS
      (INHIBITION REACTIONS).
AB  - Experiments are described which confirm the result that the specificity of
      inhibitory reactions involving substituted aromatic acids is decidedly influenced
      by the position of the substituent. When antigens with specific groups of very
      simple constitution are used for the tests, inhibiting effects are obtained also
      with substances distantly related to those determining the reactivity of the
      antigens. On the other hand, if antigens are built up from protein and chemical
      compounds of somewhat higher complexity, the specificity of the inhibition
      reactions with synthetic crystallized substances is of the same order as that of
      the usual serum reactions; in other words, it is possible to distinguish such
      compounds by serological tests as readily as proteins can be differentiated with
      the aid of precipitating sera.

PMID- 19869918
TI  - TYPHUS FEVER : III. THE BEHAVIOR OF RICKETTSIA PROWAZEKI IN TISSUE CULTURES.
AB  - Typhus Rickettsiae are found in large numbers in sections of tissue cultures of
      scrotal sac exudate. Extensive multiplication of the organisms occurs, and new
      cells become infected. Organisms are seen in cells undergoing mitotic division.
      The organisms usually become less numerous after the 6th day in vitro, but in one
      instance organisms were extremely numerous on the 16th and 21st days. Rickettsiae
      in tissue cultures retain their intracellular location, even when infection is
      very heavy. They multiply exclusively in non-phagocytic cells which are believed
      to be of mesothelial origin. Pleomorphism is much more pronounced in tissue
      cultures than in guinea pig tissues and is entirely comparable to that seen in
      the louse.

PMID- 19869919
TI  - DIFFERENTIATION BETWEEN CERTAIN TOXIC PROPERTIES OF FILTRATES OF HEMOLYTIC
      STAPHYLOCOCCUS AUREUS.
AB  - 1. Sterile filtrates from certain hemotoxic strains of Staphylococcus aureus have
      several toxic properties, of which the most important are the hemotoxic, the
      necrotoxic, the leucocidic and the property of killing rapidly. 2. The necrotoxic
      action appears to be caused by a constituent in the filtrates different from
      either the hemotoxic or the leucocidic one.

PMID- 19869920
TI  - THE GROWTH AND DEATH OF TISSUE CULTURES EXPOSED TO SUPRANORMAL TEMPERATURES.
AB  - In a study of the growth of chicken osteoblasts in cultures exposed to
      supranormal temperatures of 42 degrees C., 44 degrees C., 47 degrees C., 50
      degrees C., and 52 degrees C., it has been observed that: 1. There is no lethal
      effect after prolonged exposures at 42 degrees C. and 44 degrees C. 2. Cultures
      are killed after an exposure of 105 minutes at 47 degrees C., of 6 minutes at 50
      degrees C., and of 3.5 minutes at 52 degrees C. 3. A definite inhibition of
      growth occurs after different exposures at all temperatures from 44 degrees C.
      onwards (see Table I). 4. There is a latent period of approximately 24 hours
      before any discernible effect of sublethal or just lethal exposures; this latent
      period appears to be independent of the duration of the sublethal exposure and of
      the temperature. 5. The high temperature coefficients for lethal exposures and
      for exposures just sufficient to inhibit growth indicate an underlying
      "destructive" process in the cells of the culture.

PMID- 19869921
TI  - THE INDUCED DEVELOPMENT AND HISTOGENESIS OF PLASMA CELLS.
AB  - As result of finding numerous plasma cells in the omenta of rabbits injected with
      tuberculo-protein, a method to induce the production of large numbers of these
      cells has been discovered. The tissues in which they were pronouncedly increased
      were the subserosal connective tissues of the omentum, body wall, and intestinal
      wall. The precursor of the plasma cells is a primitive connective tissue cell. As
      this cell develops into the typical Marshalko plasma cell there is a progressive
      increase in the basophilia of the cytoplasm, the nucleus becomes eccentric, a
      condensation of the chromatin occurs near the nuclear membrane, and there is a
      loss of the nucleoli. At the time when the nucleus assumes the eccentric
      position, the clear area appears in the center of the cytoplasm. The early cells
      are capable of reproducing themselves by mitosis, while the typical mature cells
      divide by amitosis. The mature plasma cells often have muddy, spongy cytoplasm
      which contains acidophilic or hyaline granules as the cells grow old or begin to
      degenerate. The cells with granules or hyaline bodies usually have pycnotic or
      fragmented nuclei. These cells are the final stage reached by some plasma cells.
      Others, when degenerating, show vacuoles and signs of senility. Those with the
      granules and hyaline bodies are the so called Russell body cells. Plasma cells
      developed in greatest numbers after our largest injections of tuberculo-protein.
      The differentiation into young, mature, and senile forms was most clearly
      recognizable when some days had been allowed to elapse after the last large
      injection of the stimulating agent. A description of the plasma cell as viewed
      supravitally has been given. The cells are met in the blood stream as well as in
      the tissues. They are characterized by their deep yellowish gray cytoplasm,
      indistinct eccentrically placed nuclei, and large numbers of mitochondria. The
      plasma cells differ from lymphocytes, in that they did not develop in large
      numbers after direct stimulation of the lymph nodes with tuberculo-protein. The
      young plasma cells also differ in morphology from the young lymphocytes. When
      plasma cells were found in the lymph nodes they were in the connective tissue
      cords. The plasma cell is a definite entity, having a maturation cycle. It is
      stimulated to great proliferation by certain toxic irritants.

PMID- 19869922
TI  - SWINE INFLUENZA : I. EXPERIMENTAL TRANSMISSION AND PATHOLOGY.
AB  - Swine influenza has been induced in pigs by the intranasal instillation of
      material from spontaneous cases of the disease as occurring epizootically in
      eastern Iowa. The experimental disease has the same features as the epizootic. It
      has been maintained for study by serial passages accomplished either by
      intranasal instillation or by pen contact. Eight strains of the virus have been
      established experimentally during three epizootic periods. The clinical disease
      induced by these eight strains has been in general the same although its severity
      and mortality have varied. The principal features of the pathology of swine
      influenza are an exudative bronchitis accompanied by marked damage of the
      bronchial epithelium and its cilia, a peribronchial round cell infiltration, and
      massive pulmonary atelectasis. The latter is modified somewhat by a round cell
      infiltration of the alveolar walls. The lymph nodes, especially the cervical and
      mediastinal ones, are hyperplastic and edematous. There is usually a mild to
      moderate, acute splenic tumor. The mucosa of the stomach and colon is congested.
      The pneumonia following swine influenza is, characteristically, lobular in type
      and of the same general distribution as the atelectasis. The non-pneumonic areas
      of lung are extremely edematous and congested.

PMID- 19869923
TI  - SWINE INFLUENZA : II. A HEMOPHILIC BACILLUS FROM THE RESPIRATORY TRACT OF
      INFECTED SWINE.
AB  - 1. A hemophilic bacillus has been regularly obtained in culture from the
      respiratory tract of a series of swine experimentally infected with swine
      influenza and from a small number of spontaneous field cases of the disease. It
      has not been observed in respiratory tract cultures from a group of swine free
      from influenza. 2. The cultural and morphological characters of the organism have
      been described and the name Hemophilus influenzas (variety suis) suggested. The
      organism exhibits marked serological diversity, since only two out of eight
      strains studied were serologically identical. It is usually non-pathogenic for
      rabbits and white rats, and irregularly pathogenic for white mice. One strain of
      the organism was pathogenic for guinea pigs while two others were not. 3. Eleven
      out of thirteen attempts to induce symptoms of disease in swine by intranasal
      inoculation with pure cultures of H. influenzae suis were entirely negative. The
      remaining two attempts which suggested a positive result have been discussed. 4.
      Attention has been called to the marked similarity which exists between non-indol
      producing strains of H. influenzae and H. influenzae suis.

PMID- 19869924
TI  - SWINE INFLUENZA : III. FILTRATION EXPERIMENTS AND ETIOLOGY.
AB  - 1. It has been possible to demonstrate, in Berkefeld filtrates of infectious
      material from experimental cases of swine influenza, a virus which when
      administered intranasally to susceptible swine induced a mild, usually afebrile
      illness of short duration. The changes in the respiratory tract resembled those
      in swine influenza but were usually much less extensive. When the filtrable virus
      was mixed with pure cultures of H. influenzae suis and administered to swine a
      disease identical clinically and pathologically with swine influenza was induced.
      The data presented indicate that the filtrable virus of swine influenza and H.
      influenzae suis act in concert to produce swine influenza and that neither alone
      is capable of inducing the disease. 2. One attack of swine influenza usually
      renders an animal immune to reinfection. Blood serum from an animal made immune
      in this way neutralizes infectious material from swine influenza in vitro, as
      shown by the failure of the mixture to produce disease in a susceptible animal.
      3. The virus can be stored in a dried state or in glycerol for several weeks at
      least. In one instance dried material apparently retained both the virus and H.
      influenzas suis in viable form for a period of 54 days. 4. Fatal cases of
      experimental swine influenza have been observed in which H. influenzae suis was
      the only organism that could be cultivated from the respiratory tract. 5.
      Attention has been called to some features of marked similarity between epizootic
      swine influenzae and epidemic influenzae in man.

PMID- 19869925
TI  - THE SPECIFIC CYTOTOXIC ACTION OF TUBERCULIN IN TISSUE CULTURE.
AB  - Tuberculin from the human and from the bovine type of tubercle bacilli inhibits
      the growth of cells from explants of bone marrow, spleen and testes of
      tuberculous guinea pigs, and is toxic for these cells, but has no effect on
      explants of the same tissues from non-tuberculous animals. "Tuberculin" from
      other acid-fast bacteria has no inhibitory or toxic action on explants of tissues
      from either tuberculous or non-tuberculous guinea pigs. Tuberculins from the
      avian, bovine and human types of tubercle bacillus as well as "tuberculin"
      prepared from the Duval and from the Kedrowsky strains of M. leprae inhibit the
      growth of the cells of explants of the spleen and bone marrow of tuberculous
      fowls and are toxic for these cells, but have no effect on the explants from
      tissues of non-tuberculous chickens. "Tuberculins" from other acid-fast bacteria
      have no effect on the growth of explants of tissues from tuberculous or from non
      tuberculous fowls. Tissue culture methods indicate that the sensitivity of
      tuberculous tissues to tuberculin is inherent in the cell, and that it cannot be
      passively transferred.

PMID- 19869926
TI  - THE HISTOPATHOLOGY OF NUTRITIONAL ENCEPHALOMALACIA OF CHICKS.
AB  - Whatever may be the nature of the nutritive error or deficiency which in chicks
      is responsible for encephalomalacia, the immediate cause must be looked for in
      some agent or condition which impairs the capillary circulation of the brain. The
      essential lesion is an ischemic necrosis, followed, if the animal survive, by
      reparative organization of the dead tissue.

PMID- 19869927
TI  - PRODUCTION OF A REFRACTORY STATE AS CONCERNS THE SHWARTZMAN PHENOMENON BY THE
      INJECTIONS OF VENOM OF THE MOCCASIN SNAKE (ANCISTRODON PISCIVORUS).
AB  - The majority of rabbits receiving intradermal, intraperitoneal or intravenous
      injections of moccasin venom became refractory to the development of the
      Shwartzman phenomenon. An incubation period of about 14 days was required for
      their resistance to develop. The incidence of refractory animals was inversely
      proportional within limits to the amount of toxin given intravenously to elicit
      the Shwartzman phenomenon. The intravenous route was the most efficacious in
      developing refractivity. The refractory state was still present 44 days after the
      primary injection of moccasin venom. Rattlesnake venom was not efficacious in
      inducing a refractory state. The refractory animals did not show a changed
      reaction to moccasin venom in the concentrations used. No circulating antibodies
      could be demonstrated to explain the refractory state. Antivenin had no effect on
      the course of the Shwartzman phenomenon.

PMID- 19869928
TI  - IS THE RAT DERMATITIS CONSEQUENT ON VITAMIN B(2) (G) DEFICIENCY TRUE PELLAGRA?
AB  - 1. Isolated cases of a dermatitis resembling histologically that of human
      pellagra have occurred in rats supplied with sufficient vitamin B(2) (G) in the
      form of beef extract or neutral autoclaved yeast to produce good growth. 2. Other
      rats on basal diets containing similarly prepared nutrients but deprived of any
      known source of vitamin B(2) (G) develop a dermatitis similar in appearance to
      that described by other workers, but this skin effect differs in histological
      picture from that found in human pellagra or in black tongue of dogs. These rats
      showed growth failure which supports the view that they lacked growth-promoting
      vitamin B(2) (G). 3. It is suggested that dermatitis in rats may be of diverse
      type; one resulting from vitamin B(2) (G) deficiency quite different
      histologically from human pellagra, and one closely allied to human pellagra and
      black tongue in dogs due to lack of some at present unidentified factor.

PMID- 19869929
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : IV. THE
      SYNTHESIS OF THEp-AMINOBENZYL ETHER OF THE SOLUBLE SPECIFIC SUBSTANCE OF TYPE III
      PNEUMOCOCCUS AND ITS COUPLING WITH PROTEIN.
AB  - 1. The p-amino and p-nitromonobenzyl ethers of the specific polysaccharide of
      Type III Pneumococcus have been prepared. 2. The diazonium ether of the specific
      polysaccharide has been coupled with serum globulin to yield a specific
      polysaccharide-protein complex and this complex has been used for immunization.
      The results of the immunological studies are presented in the following paper.

PMID- 19869930
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : V. THE
      IMMUNOLOGICAL SPECIFITY OF AN ANTIGEN PREPARED BY COMBINING THE CAPSULAR
      POLYSACCHARIDE OF TYPE III PNEUMOCOCCUS WITH FOREIGN PROTEIN.
AB  - 1. Type-specific antipneumococcus immunity has been induced in rabbits by
      immunization with antigen prepared by combining a specific derivative of the
      capsular polysaccharide of Type III Pneumococcus with globulin from horse serum.
      2. Rabbits immunized with this antigen acquire active immunity against infection
      with virulent Type III pneumococci. 3. The sera of the immune rabbits contain
      type-specific antibodies which precipitate the Type III capsular polysaccharide,
      agglutinate Type III pneumococci, and specifically protect mice against Type III
      infection. 4. The experimental data are discussed with reference to: (1) the
      concurrence in the immune sera of type-specific antibodies for Pneumococcus and
      precipitins for horse globulin; (2) the determining influence of the capsular
      polysaccharide on the specificity of the antigen as a whole; (3) the unity of the
      type-specific precipitins, agglutinins, and protective antibodies induced by a
      single component of the pneumococcus in chemical union with an unrelated, animal
      protein.

PMID- 19869931
TI  - SOME ULTRAVIOLET PHOTOMICROGRAPHS OF B. SUBTILIS.
AB  - 1. Type-specific antipneumococcus immunity has been induced in rabbits by
      immunization with antigen prepared by combining a specific derivative of the
      capsular polysaccharide of Type III Pneumococcus with globulin from horse serum.
      2. Rabbits immunized with this antigen acquire active immunity against infection
      with virulent Type III pneumococci. 3. The sera of the immune rabbits contain
      type-specific antibodies which precipitate the Type III capsular polysaccharide,
      agglutinate Type III pneumococci, and specifically protect mice against Type III
      infection. 4. The experimental data are discussed with reference to: (1) the
      concurrence in the immune sera of type-specific antibodies for Pneumococcus and
      precipitins for horse globulin; (2) the determining influence of the capsular
      polysaccharide on the specificity of the antigen as a whole; (3) the unity of the
      type-specific precipitins, agglutinins, and protective antibodies induced by a
      single compo of the pneu mococcus in chemical union with an unrelated, animal
      protein.

PMID- 19869932
TI  - CULTIVATION OF VACCINE VIRUS FOR JENNERIAN PROPHYLAXIS IN MAN.
AB  - 1. A dermal strain of vaccine virus has been adapted to a simple culture medium
      consisting of minced chick embryo suspended in Tyrode's solution. 2. The bacteria
      free culture virus, thus obtained, produces in lower animals and in man typical
      vaccinia that renders them refractory to infection with ordinary vaccine virus
      harvested from calves.

PMID- 19869933
TI  - SPECIFICITY OF THE PRECIPITIN REACTION IN TOBACCO MOSAIC DISEASE.
AB  - 1. Leaf extracts of Sudan grass, Hippeastrum equestre Herb., lily, and Abutilon
      striatum Dicks. (A. Thompsoni hort.), each affected with its respective mosaic
      disease, and peach affected with yellows disease, were tested for their ability
      to precipitate antiserum for virus extract of tobacco mosaic disease. No
      precipitate occurred. 2. Nicotiana glutinosa L., N. rustica L., and Martynia
      louisiana Mill. were added to the list of hosts of tobacco mosaic virus which
      have been tested with antiserum for the same virus in N. tabacum L. var. Turkish.
      The object was to determine the presence or absence of material reacting with the
      specific precipitins such as that already demonstrated in extracts of tomato,
      pepper, and petunia affected with the same virus. The presence of specific
      substances was demonstrated in every case. 3. The viruses of ringspot and
      cucumber mosaic diseases were multiplied in Turkish tobacco and leaf extracts of
      the affected plants were used in turn as antigens in precipitin tests with
      antiserum for tobacco mosaic virus extract of Turkish tobacco. A slight
      precipitation resulted in the tubes containing undiluted antiserum and virus
      extract such as occurs when juice from normal tobacco is used with undiluted
      antiserum. No precipitate was demonstrable that was specific for virus extracts
      of tobacco affected with either ringspot or cucumber mosaic disease. 4. The
      results favor the interpretation that the specific antigenic substance in virus
      extract of tobacco mosaic disease is foreign antigenic material, possibly virus
      itself, not altered host protein.

PMID- 19869934
TI  - STUDIES ON THE BLOOD CYTOLOGY OF THE RABBIT : VIII. THE BLOOD OF NORMAL RABBITS
      AS AN INDEX OF THEIR RESISTANCE TO A TRANSPLANTABLE NEOPLASM.
AB  - 1. The blood cytology of 91 rabbits was studied prior to inoculation with a
      transplantable malignant neoplasm. The following statements refer in each
      instance to the mean values of the pre-inoculation counts. 2. The animals which
      were most resistant to the malignant disease had, before inoculation, normal red
      and white cell counts, normal hemoglobin percentages, high eosinophile counts,
      and low counts of monocytes and lymphocytes. The relations of the neutrophile and
      basophile counts were irregular, but normal values also appeared to be associated
      with greater resistance. 3. The most susceptible animals were those which had,
      before inoculation, red cell counts above 5,500,000 or below 5,000,000 per c.mm.;
      hemoglobin above 70 per cent or below 60 per cent (Newcomer); white cell counts
      below 6,000 or above 8,500 per c.mm.; low eosinophile, high monocyte, or high
      lymphocyte counts. 4. No animal with any of the following findings prior to
      inoculation recovered completely from the tumor as determined by autopsy
      examination: red cells above 5,500,000 per c.mm. of blood; hemoglobin above 70
      per cent; total white cells above 10,000 per c.mm.; eosinophiles below 120 per
      c.mm., or below the relative value of 1.5 per cent; basophiles below 400 per
      c.mm., or below the relative value of 6 per cent; lymphocytes above 3,600 per
      c.mm.; monocytes above 1,500 per c.mm.; neutrophiles above 5,000 per c.mm.; and
      total granular cells above 5,700 per c.mm. In the case of each of the following
      pre-inoculation values, only 1 animal was completely free from tumor at autopsy:
      hemoglobin below 60 per cent; red cells below 4,800,000 per c.mm.; total granular
      cells below 3,300 per c.mm.; total non-granular cells below 2,300 per c.mm.;
      total non-granular cells above 3,700 per c.mm. No animal with pre-inoculation
      eosinophiles above 3.9 per cent, or basophiles above 16 per cent died from the
      tumor. 5. The blood findings before inoculation could be related to the character
      and outcome of the malignant disease, from the standpoint of animal groups as
      well as in the case of individual rabbits. 6. From the results of the experiments
      here reported, it seems possible to predict with an accuracy of between 80 and 90
      per cent the individual resistance or susceptibility of rabbits to the tumor by a
      study of their blood cells before inoculation.

PMID- 19869935
TI  - THE EFFECT OF TESTICLE EXTRACT AND OF NORMAL SERUM ON A TRANSPLANTABLE EPITHELIAL
      TUMOR OF THE RABBIT.
AB  - Extract of rat, rabbit or bull testicle prevents or retards the growth of a
      rabbit tumor when a mixture of the extract and a tumor cell suspension is
      inoculated intradermally. Similar mixtures, made with normal rabbit serum instead
      of testicle extract, give rise to tumors which grow with unusual rapidity. The
      results are the opposite of those obtained with pathogenic bacteria or filtrable
      viruses which are enhanced by testicle extract and generally inhibited by normal
      serum.

PMID- 19869936
TI  - THE GRADIENT OF VASCULAR PERMEABILITY : IV. THE PERMEABILITY OF THE CUTANEOUS
      VENULES AND ITS FUNCTIONAL SIGNIFICANCE.
AB  - The permeability of the venules of the skin of the mouse greatly exceeds that of
      the capillaries. A mounting gradient of permeability exists along the further
      portion of the latter. The significance of these facts is discussed with relation
      to conditions in human skin. The cutaneous venules are differentiated for several
      functions besides those ordinarily attributed to them, and must be considered as
      specialized organs.

PMID- 19869937
TI  - PROTEIN FRACTIONS OF A SCARLATINAL STRAIN OF STREPTOCOCCUS HEMOLYTICUS.
AB  - 1. A tentative method is described for extracting a labile nucleo-protein from
      scarlatinal Streptococcus hemolyticus. 2. The product differs chemically and
      serologically from the fractions prepared by subsequent alkaline extraction of
      the cell residues, and from protein obtained by the classical method for
      extraction of bacterial "nucleoproteins." 3. The new nucleoprotein is sensitive
      to very weak alkalies and readily loses nucleic acid under these conditions. The
      protein degradation products resemble the alkaline-extracted protein fractions of
      the cell residues. 4. The bearing of the properties of the new nucleoprotein on
      the chemistry of nucleoproteins in general is discussed, also the possible
      relation of the fractions obtained to the analysis of streptococcus antigens made
      by Lancefield.

PMID- 19869938
TI  - THE USE OF MICE IN TESTS OF IMMUNITY AGAINST YELLOW FEVER.
AB  - 1. A method of testing sera for protective power against yellow fever is
      described and designated as the intraperitoneal protection test in mice. 2. The
      test consists essentially of the inoculation of mice intra-peritoneally with
      yellow fever virus, fixed for mice, together with the serum to be tested, and the
      simultaneous injection of starch solution into the brain to localize the virus.
      If the serum lacks protective power the mice die of yellow fever encephalitis. 3.
      The test is highly sensitive. Consequently it is useful in epidemiological
      studies to determine whether individuals have ever had yellow fever and in tests
      to find whether vaccinated persons or animals have in reality been immunized. 4.
      When mice were given large intraperitoneal injections of yellow fever virus fixed
      for mice, the virus could be recovered from the blood for 4 days although
      encephalitis did not occur. If the brain was mildly injured at the time of the
      intraperitoneal injection, the symptoms of yellow fever encephalitis appeared 6
      days later, but the virus was then absent from the blood. 5. Strains of white
      mice vary greatly in their susceptibility to yellow fever.

PMID- 19869939
TI  - STUDIES ON THE FILTRABILITY OF BACTERIUM GRANULOSIS.
AB  - The evidence hitherto reported concerning the filtration of trachomatous
      material, and inoculation of man and monkeys with the filtrates points to the
      conclusion that the incitant of trachoma is not, as a rule, filtrable. Our
      findings confirm this view and indicate further that no virus causing the disease
      is adsorbed to Bacterium granulosis. On the other hand, Bacterium granulosis
      itself in heavy suspensions is irregularly filtrable through Berkefeld V candles,
      like some other bacteria (14), but it is present in the filtrates in only small
      numbers. When suspensions were used of trachomatous human and monkey tissues,
      which contain much fewer organisms than do actual cultures, Bacterium granulosis
      was never recovered from the filtrates. The conception that trachoma is a disease
      caused by an ultramicroscopic virus is based on (a) the positive results of
      filtration in two animals, as reported by Nicolle and his coworkers, and (b) the
      presence of so called "inclusion bodies" in some of the cells of the lesions. One
      can state definitely that the evidence is now greatly against the filtrability of
      the etiological agent of trachoma. Furthermore, filtrability does not in itself
      suffice for the classification of an agent as an ultramicroscopic virus.
      Concerning (b), a vast literature has accumulated which indicates that the
      "inclusion bodies" of trachoma are not specific for the disease and that the
      bodies themselves may be bacterial in origin (15). We have not as yet found
      bodies of the kind characteristic of many filtrable viruses in the tissues of man
      or of monkeys with the experimental disease.

PMID- 19869940
TI  - THE TRANSMISSION OF THE VIRUS OF MEXICAN TYPHUS FROM RAT TO RAT BY POLYPLAX
      SPINULOSUS.
AB  - Polyplax spinulosus, the common rat louse, is easily infected with the virus of
      typhus by feeding on infected rats. As in the case of Pediculus humanus, such
      feedings are followed by the appearance of large numbers of Rickettsia prowazeki
      within the gut of the insect. The virus of Mexican typhus can be transmitted from
      rat to rat by Polyplax spinulosus by methods of feeding simulating natural
      conditions. It seems, therefore, that this ectoparasite is an important factor in
      maintaining an endozoic of Mexican typhus among wild rats.

PMID- 19869941
TI  - STUDIES ON THE RELATIONSHIP OF CERTAIN VARIANTS OF B. TYPHOSUS : I. AGGLUTINATION
      AND AGGLUTININ ABSORPTION.
AB  - The results of cross-agglutination and agglutinin absorption experiments with the
      motile smooth, non-motile smooth, motile rough, and non-motile rough forms of B.
      typhosus are presented. Cross-agglutination between these four forms is complete,
      save that the motile rough antigen is under certain conditions only weakly
      agglutinated by the antisera prepared with the non-motile forms. Cross-absorption
      of the somatic agglutinogen of the four variants is complete, save that the
      motile smooth culture still shows granular agglutination with the anti-MS and
      anti-MR sera after absorption with these cultures. A theory of the antigenic
      composition of the four variants of B. typhosus is presented, based on the
      results obtained in these experiments. It would appear that, contrary to the
      usually accepted theory, the four variants have a common somatic agglutinogen. To
      explain the difference between the smooth virulent forms and the rough non
      virulent forms it has been assumed that the S forms contain a carbohydrate which
      is associated with virulence and which takes no part in the agglutination
      reaction.

PMID- 19869942
TI  - CUTANEOUS REACTIONS IN RABBITS TO THE TYPE-SPECIFIC CAPSULAR POLYSACCHARIDES OF
      PNEUMOCOCCUS.
AB  - The injection of the type-specific capsular polysaccharides of Pneumococcus Types
      I, II and III into the skin of rabbits, actively or passively immunized to one of
      these types of Pneumococcus, elicits a type-specific cutaneous reaction. The form
      of reaction resembles that described by Arthus. The reaction is produced only
      when type-specific precipitins for the homologous polysaccharide are demonstrable
      in the blood of the rabbit. In 84 per cent of actively immunized rabbits, the
      serum of which contained type-specific precipitins, a reaction was elicited. A
      positive result was obtained in 100 per cent of rabbits passively immunized with
      antipneumococcus horse serum whereas, attempts passively to transfer reactivity
      from immune rabbit to normal rabbit were unsuccessful. The recipients, in the
      latter group, possessed no demonstrable circulating type-specific precipitins.
      The reaction produced by specific capsular carbohydrates is always associated
      with a well grounded type-specific immunity. A brief summary of the relation of
      hypersensitiveness and immunity to pneumococcus is given.

PMID- 19869943
TI  - SERUM SICKNESS IN RABBITS : I. MANIFESTATIONS OF SERUM SICKNESS.
AB  - 1. The injection of a single large dose of normal horse serum into rabbits
      results in the appearance 3 to 8 days later of erythematous and edematous
      reactions on the ears in 68.9 per cent of the animals. 2. The injections may be
      given by any of several routes and reactions appear when the site of injection is
      definitely distant from the ears. 3. Injections of various antisera into rabbits
      cause the appearance of similar reactions. 4. These reactions can be considered
      as manifestations of serum sickness in rabbits.

PMID- 19869944
TI  - DURATION OF DEMONSTRABLE ANTIBODIES IN THE SERUM OF RABBITS IMMUNIZED WITH HEAT
      KILLED TYPE I PNEUMOCOCCI.
AB  - In rabbits immunized by the injection of suspensions of heat-killed pneumococci
      the results obtained as regards not only the development of agglutinating and
      mouse protective antibodies, but also the persistence of these bodies in the
      blood depend to a considerable extent upon the route of immunization and the size
      of the inocula. Agglutinins may appear in the sera of all the rabbits except
      those inoculated subcutaneously, but in most instances they disappear within a
      short time. Protective antibodies appear in the sera of all rabbits, no matter
      which route of injection be employed and they persist much longer than do the
      agglutinins. They persist longest when the injections are made intravenously or
      intraperitoneally and are of briefest duration when the injections are made
      subcutaneously.

PMID- 19869945
TI  - LOCALIZATION OF PNEUMOCOCCI IN THE LUNGS OF PARTIALLY IMMUNIZED MICE FOLLOWING
      INHALATION OF PNEUMOCOCCI.
AB  - 1. When mice are passively immunized by the intraperitoneal injection of
      antipneumococcus horse serum or actively by the injection of heat-killed
      pneumococcus cultures, and are then alcoholized and sprayed with a culture of
      pneumococci of the same type as that of the bacteria employed in immunization, a
      considerable number die with localized lesions in the lungs. 2. If instead of
      injecting immune serum of the type corresponding to that of the bacteria employed
      in producing the infection, normal horse serum or immune serum of a heterologous
      type be injected, or if the animals be previously immunized by the injection of
      killed pneumococci of a heterologous type, none of the animals which die show any
      evidence of localization of the infection in the lung. 3. The occurrence of
      pulmonary lesions in alcoholized mice after spraying with a culture of
      pneumococci is the consequence of a general immunity of a very mild grade.

PMID- 19869946
TI  - THE ESTABLISHMENT OF AN ALBINO RAT COLONY FREE FROM MIDDLE EAR DISEASE.
AB  - A special colony of albino rats was built up by selection and isolation from a
      population in which middle ear disease was highly prevalent. No cases of aural
      infection occurred in the selected group, whereas its precursor showed a crude
      incidence of 57 per cent. The subjection of selected rats to a rachitic diet and
      to overcrowding did not predispose to the development of middle ear disease. The
      incidence of pneumonia was not similarly affected; thus, 52 per cent of the adult
      selected rats showed pulmonary lesions, and 78 per cent of the adult stock rats.
      There was, however, a significant reduction in the number of cases which showed
      advanced pulmonary lesions. Certain theoretical considerations of middle ear
      disease and of pneumonia are discussed.

PMID- 19869947
TI  - SPECIFIC CUTANEOUS REACTIONS AND CIRCULATING ANTIBODIES IN THE COURSE OF LOBAR
      PNEUMONIA : I. CASES RECEIVING NO SERUM THERAPY.
AB  - 1. A group of 41 non-serum treated patients with Type I, II or III pneumococcus
      pneumonia were studied during their disease and convalescence with respect to
      their skin reactions to specific pneumococcus polysaccharides and, in most
      instances, for the presence of circulating agglutinins and protective antibodies
      for all these 3 types. 2. One-half of the Type I and two-thirds of the Type II
      and Type III recovered cases gave the typical immediate "wheal and erythema"
      response to the homologous polysaccharide at or about the time of recovery. All
      cases tested showed protective antibodies and almost all showed agglutinins for
      the homologous pneumococcus. In the fatal cases, in general, positive cutaneous
      reactions and circulating antibodies were not obtained. 3. In cases of pneumonia
      receiving repeated cutaneous inoculations with various types of specific
      polysaccharide, antibodies for pneumococci differing from the infecting type but
      corresponding to the types of carbohydrate injected were present 1 week or later
      after such injections. These heterologous antibodies were most frequently
      demonstrated for Type II and were probably the result of immunization by means of
      the cutaneous injections. 4. Positive skin responses to homologous
      polysaccharides and corresponding circulating antibodies were demonstrated with
      similar frequency in the first 3 weeks after crisis in patients who had not
      previously received intracutaneous injections. In such patients heterologous
      antibodies were rarely found. 5. Typical skin reactions with the specific
      pneumococcus polysaccharides and mouse protective antibodies were demonstrated
      independently in a number of hospital patients who had had no recent history of
      pneumonia. 6. Some patients with demonstrable foci of persistent infection or
      with latent infections which later proved fatal showed positive cutaneous
      responses to the homologous type polysaccharide and circulating specific
      antibodies for the corresponding type. 7. The agglutination test, though less
      sensitive than the mouse protection test for determining the presence of
      antibody, has many advantages over the latter and is simplest to use in following
      the course of the untreated pneumonia.

PMID- 19869948
TI  - SPECIFIC CUTANEOUS REACTIONS AND CIRCULATING ANTIBODIES IN THE COURSE OF LOBAR
      PNEUMONIA : II. CASES TREATED WITH ANTIPNEUMOCOCCIC SERA.
AB  - 1. Characteristic cutaneous responses to the type-specific protein-free
      carbohydrates of both Type I and Type II pneumococci have been "produced" in
      cases of lobar pneumonia due to either of these types by the intravenous
      injection of concentrated bivalent (Types I and II) antipneumococcic sera
      (Felton). 2. A positive cutaneous response to the specific polysaccharide of Type
      II pneumococci has been passively transferred from human cases convalescing from
      this infection to a patient suffering from pneumonia due to this organism. 3. The
      cutaneous responses to the type-specific polysaccharides and circulating
      antibodies were studied in 51 cases of lobar pneumonia. Positive cutaneous
      reactions were, in most instances, associated with recovery, even when purulent
      complications were present. Failure to elicit a positive reaction was usually
      followed by a fatal outcome. 4. The positive reactions in patients who were
      treated with concentrated sera and recovered were most often elicited within 24
      hours after the first dose and after a total of 40 cc. had been given. 5. The
      positive skin reactions obtained after the administration of specific antisera
      were associated with the presence of mouse protective antibodies and agglutinins
      in the sera of the patients. 6. The immune reactions in serum treated cases
      receiving repeated inoculations with the specific carbohydrates disappeared more
      rapidly than in similar cases receiving no antiserum. It is suggested that the
      administration of antisera in someway interferes with the production of
      antibodies by the intracutaneously injected carbohydrates.

PMID- 19869949
TI  - ARTIFICIAL ACIDOSIS IN TRYPANOSOMA LEWISI INFECTIONS, AND ITS BEARING ON THE
      PATHOGENIC ACTION OF TRYPANOSOMA EQUIPERDUM.
AB  - When the alkali reserve is artificially lowered in rats infected with Trypanosoma
      lewisi, the number of parasites in the blood is increased. The increase is large
      in the early stages of the disease, and becomes less marked as the number crisis
      is approached. Near the crisis, and after it, a lowered alkali reserve does not
      affect the number of trypanosomes. It has been shown that the observed increase
      does not result from a contraction of the capillaries of the inner organs, which
      would throw a large number of trypanosomes into the peripheral circulation; nor
      is the increase due to a greater reproductive activity on the part of the
      trypanosomes. The increase must, therefore, be due to an inhibition of the
      destructive forces of the host. It is suggested that the known production of
      organic acids by the pathogenic trypanosomes plays a similar role in inhibiting
      the destructive mechanism of the host, and is therefore of significance in the
      pathogenic activity of these organisms.

PMID- 19869950
TI  - IN VITRO TRANSFORMATION OF PNEUMOCOCCAL TYPES : I. A TECHNIQUE FOR INDUCING
      TRANSFORMATION OF PNEUMOCOCCAL TYPES IN VITRO.
AB  - 1. Type-specific S pneumococci may be transformed from one specific S type into
      other specific S types entirely by in vitro methods. 2. R forms of pneumococci,
      derived from S forms of one specific type, may be transformed into S forms of
      other specific types by the following in vitro procedure:-the growth of small
      inocula of R forms in media containing vaccines prepared from heterologous S
      cultures. 3. Transformation of type may be effected in this procedure by the use
      of small quantities of S vaccine,-quantities representing the bacteria from as
      little as 0.1 cc. of the original culture. 4. Transformation of type, as induced
      by this procedure, is most readily effected by employing anti-R serum in the
      culture medium. Transformation of type may be effected, however, in media which
      do not contain anti-R antibodies. 5. Previous findings on the thermal
      characteristics of the property of S vaccines responsible for transformation of
      type have been confirmed and extended.

PMID- 19869951
TI  - IN VITRO TRANSFORMATION OF PNEUMOCOCCAL TYPES : II. THE NATURE OF THE FACTOR
      RESPONSIBLE FOR THE TRANSFORMATION OF PNEUMOCOCCAL TYPES.
AB  - 1. Further observations on the conditions under which transformation of
      pneumococcal types may be induced by in vitro procedures are presented. 2. R
      cultures possessing only slight degrees of R stability are most suitable for
      transformation purposes by in vitro procedures. 3. Vaccines prepared from
      cultures subjected to the action of bacterial enzymes liberated (a) in old broth
      cultures, (b) during mechanical disruption of young bacterial cells, are not
      effective in inducing transformation of type. 4. The property of an S vaccine
      responsible for transformation of type is not related to the specific soluble
      substance of pneumococcus. 5. Attempts to effect transformation of type by the
      use of cell-free extracts of pneumococcus have so far proved unsuccessful.

PMID- 19869952
TI  - PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: AN ANTIBODY AUXILIARY
      TO SERUM NEUTRALIZATION OF MENINGOCOCCUS REACTING FACTORS.
AB  - In. this paper there is described an antibody auxiliary to the neutralization of
      meningococcus reacting factors. The presence of the antibody facilitates studies
      on neutralizing potency of antimeningococcus sera. There is also reported a non
      specific neutralizing factor of a heterologous immune serum, which can be
      differentiated from specific neutralizing antibodies of antimeningococcus sera.
      Its nature and connection with the auxiliary antibody remain to be determined.

PMID- 19869953
TI  - A SEROLOGICAL STUDY OF THE POLYSACCHARIDES OF MENINGOCOCCUS, B. ANTHRACIS, B.
      PROTEUS, B. SUBTILIS AND B. MESENTERICUS.
AB  - 1. The meningococcus polysaccharide reacts with a broad precipitable carbohydrate
      antibody in common with those of B. anthracis, B. subtilis, B. proteus and B.
      mesentericus. 2. The anthrax and proteus polysaccharides are specific in the
      higher dilutions of serum. 3. Antianthrax serum contains two different
      polysaccharide precipitable antibodies, one specific and the other non-specific.
      4. Agglutinins have no relation to the carbohydrate precipitable substance,
      specific or non-specific. 5. An immunological method is given for the study of
      the probable chemical relation or similarity of polysaccharides of different
      bacteria similar to that given by Heidelberger, Goebel and Avery from a strain of
      Friedlander bacillus and Pneumococcus Type II.

PMID- 19869955
TI  - STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY : V. THE
      INFLUENCE OF HEREDITY UPON THE INCIDENCE OF LUNG TUMORS IN MICE.
AB  - A male mouse from a strain with a high incidence of spontaneous lung tumors was
      crossed with several females derived from a low tumor strain. The first
      generation of offspring were then backcrossed to individuals of the original
      strains. The resulting two groups of offspring differed significantly in the
      incidence of spontaneous tumors of the lung. These facts are discussed in
      relation to others previously discovered. It seems clear from the evidence
      presented that there are among mice constitutional types which differ in
      incidence of tumors of the lung and that the differences are inherited. The
      number of genetic factors involved has not been determined. No influence of sex
      was apparent. The possibility of there being genetic factors which affect tumor
      age will be dealt with later.

PMID- 19869954
TI  - ELECTROPHORESIS EXPERIMENTS WITH THE VIRUS AND PROTECTIVE BODIES OF YELLOW FEVER.
AB  - 1. When suspended in slightly alkaline (pH 7.4 to 7.8) saline dilutions of clear,
      hemoglobin-free normal monkey serum, the virus of yellow fever from infected
      monkeys and from infected, but blood-free, mosquitoes, usually acts as if it were
      possessed of a positive electrical charge. 2. The virus tends to assume a
      negative charge in fluids having a slightly acid reaction. 3. The isoelectric
      point of the virus seems to be in the neighborhood of pH 7.0, possibly ranging
      from pH 7.3 to pH 6.9. 4. Exposure to fluid having a reaction of pH 5.0 for 3
      hours appeared to inactivate the virus. 5. In experiments in which the suspending
      fluid was prepared with normal serum diluted with distilled water and containing
      a good quantity of partly hemolyzed erythrocytes, the virus tended to migrate to
      the anode. 6. The protective bodies in yellow fever immune serum appear to carry
      a negative charge in slightly alkaline saline dilutions of serum.

PMID- 19869956
TI  - HISTOLOGICAL STUDIES OF THE BONE MARROW IN FASTED AND POLYNEURITIC PIGEONS.
AB  - 1. The histological changes of the bone marrow in fasted and rice disease pigeons
      are essentially the same. 2. The histological changes of the bone marrow in pure
      vitamin B deficiency consist of degeneration and edema and slight endothelial
      proliferation of the small vascular channels, but with active hematopoiesis. 3.
      The anemia of rice disease in pigeons is in large part a starvation anemia and
      not directly related to vitamin B deficiency.

PMID- 19869957
TI  - THE IMMEDIATE EFFECTS OF UNILATERAL NEPHRECTOMY ON OPEN GLOMERULI AND URINE
      OUTPUT.
AB  - 1. Renal shock with oliguria or anuria after unilateral kidney operation has not
      been produced in seventeen rabbits. 2. For a period of 2 hours after unilateral
      nephrectomy the one kidney carries on a proportionate part of the work of the
      previous two kidneys, and there is no evidence of functional compensation. 3.
      There is a general correlation between open glomeruli and urine output.

PMID- 19869958
TI  - THE CHOLESTEROL FUNCTION OF THE GALL BLADDER.
AB  - Cholesterol determinations of gall bladder and hepatic bile obtained from the
      same source reveal a greater concentration in the former even after the
      inspissating effect of the gall bladder is allowed for. This evidence together
      with that from other experiments indicates that the gall bladder has the power to
      excrete cholesterol into its lumen. There is evidence also that infection may
      accelerate this excretion. An hypothesis is presented to explain the
      precipitation of cholesterol in the bile, and the bearing of these findings on
      the pathogenesis of cholesterol stones is briefly discussed.

PMID- 19869959
TI  - FACTORS INFLUENCING THE CORRELATION BETWEEN DIFFERENCES OF ELECTRIC POTENTIAL IN
      THE SKIN OF HUMAN SUBJECTS AND BASAL METABOLISM.
AB  - High metabolic rates are associated normally with small differences of electric
      potential, whereas low metabolic rates are associated with large differences of
      electric potential as measured on the extremities of the body. Within the normal
      range of metabolism there appears to be a definite correlation between the
      metabolic rates and the difference of electric potential over a specified area of
      the skin, provided the person under test has no abnormalities of the circulatory
      system or of the functions of the skin. If there are no dysfunctions of the
      circulation or of the skin, the metabolic rate may be calculated, within +/-4
      points, from the expression See PDF for Equation where x is the metabolic rate
      and y is the difference of electric potential across the specified areas of skin
      (electrodes 12 cm. apart). In general, there are abnormalities of the circulation
      of the blood or of the functions of the skin of persons for whom the metabolic
      rates determined by the two methods (difference of electric potentials and
      gasometric procedures) do not agree with +/-4 points. Manifest retardation or
      return to normality in the rate of circulation of the blood, such as may be
      produced by the sphygmomanometric cuff under varying pressures, produces marked
      changes in the difference of electric potentials obtained across a specified
      intervening area of skin. Retardation of flow of blood produces increased
      differences of electric potential. Preliminary investigations indicate that there
      is an inverse correlation between cutaneous temperatures and differences of
      electric potential. Day by day variations, emotive effects and the partaking of
      food have less effect, in general, on the electric potentials across a specified
      area of skin than they have on the metabolic rates. These experimental results
      indicate that there may be a more direct correlation between electric potentials
      and the circulation of the blood per se than between electric potentials and the
      metabolism of the body per se. When normality of circulation of the blood and of
      the functions of the skin exists in the areas under test for differences of
      electric potential, there is apparently a correlation between metabolic rates and
      electric potentials.

PMID- 19869960
TI  - A BACTERIOLOGICAL STUDY OF INFECTIOUS LARYNGOTRACHEITIS OF CHICKENS.
AB  - 1. The causative agent of infectious laryngotracheitis of chickens was found to
      be present in bacteriologically sterile tracheal exudate, spleens, and livers of
      diseased fowls. 2. The causative agent was present regularly in the tracheal
      exudate, in the spleens of about 60 per cent, and in the livers of about 30 per
      cent of chickens with active laryngotracheitis infection. 3. Suspensions of the
      spleen and liver were less effective in inducing the disease than those made from
      the tracheal exudate. This finding, together with the absence of pathological
      changes in the spleens and livers would seem to indicate that they are not
      actively involved but that the causative agent is carried to them by way of the
      blood. 4. The disease could, in our experience, be produced only in chickens
      Domesticated ducks and several wild and free-flying species of birds, including
      sparrows, crows, starlings, doves, and pigeons were found to be refractory, and
      so too were rabbits, guinea pigs, white rats, and one pig that was tested.

PMID- 19869961
TI  - A FILTRABLE VIRUS, THE CAUSE OF INFECTIOUS LARYNGOTRACHEITIS OF CHICKENS.
AB  - 1. Experiments have shown that tracheal exudate from two strains of
      laryngotracheitis of chickens from New Jersey and two from California when
      suspended in bouillon and passed through Berkefeld V filters will produce the
      disease. Two of six Berkefeld N filters allowed the etiological agent to pass,
      whereas four did not. Attempts to produce the disease with Seitz filtrates were
      unsuccessful. These results demonstrate that laryngotracheitis is caused by a
      filtrable virus that because of its size or some other property does not pass
      readily through the finer filters. 2. It has been shown that the sera from fowls
      that have recovered from an infection with one of the New Jersey viruses will
      neutralize the same strain and also the one California strain tested. In order to
      demonstrate neutralization conclusively it was necessary to titrate samples of
      dried virus and in the tests to use approximately ten infecting doses. 3. The
      virus dried over calcium chloride for 10 days and then stored in the refrigerator
      for 60 days produced disease. Kept over calcium chloride for a month it was still
      active and when dried by Swift's method it remained alive for 5 months.

PMID- 19869962
TI  - HISTOPATHOLOGY OF INFECTIOUS LARYNGOTRACHEITIS IN CHICKENS.
AB  - 1. The characteristic lesions of infectious laryngotracheitis are ordinarily
      restricted to the respiratory tract and are most pronounced in the larynx and
      trachea. Sometimes the eyelids are affected. A certain percentage of the cases
      are associated with bronchitis and peribronchitis, pneumonic areas and
      hemorrhages in the lung, while the involvement of the nasal passages,
      communicating sinuses, and eyes seems to be dependent upon the mode of infection
      and the course of the disease. 2. The virus affects the epithelial cells
      primarily, but soon inflammation develops in the submucosa and underlying parts.
      Edema is often extremely pronounced in the submucosa. The destruction taking
      place at later stages is due to edema, cellular infiltration, and hemorrhages,
      and in some instances to secondarily invading bacteria. 3. Characteristic
      intranuclear inclusions in the epithelial cells of the trachea are present in
      many cases. They bear a close resemblance to the inclusions occurring in herpes,
      varicella, virus III of rabbits, and submaxillary gland disease of guinea pigs.

PMID- 19869963
TI  - ACTION OF METHYLENE BLUE ON BODY TEMPERATURE AND METABOLISM.
AB  - 1. Methylene blue injected intravenously in white rats is hyperthermizing or
      hypothermizing according to the environmental temperature. 2. It causes an
      increase in metabolism at 28 degrees C. or above. At lower temperature it does
      not affect, or rather depresses, metabolism. 3. It does not seem likely that its
      hypermetabolic action is due to catalysis of cell oxidations. 4. In animals
      exposed to an atmosphere with a high partial pressure of oxygen, methylene blue
      causes pulmonary edema, much more rapidly than does oxygen alone.

PMID- 19869964
TI  - THE DEVELOPMENT AND LOCALIZATION OF THE DERMAL PNEUMOCOCCIC LESION IN THE RABBIT.
AB  - An attempt has been made to analyze the factors involved in the development and
      localization of the dermal pneumococcic lesion in the rabbit. The character and
      quantity of the edema fluid which forms during the early phases of the lesion are
      intimately concerned in its development and spread. It contains an antithrombic
      substance, probably derived from the pneumococci, and delayed coagulation
      probably facilitates its movement through the tissue. The direction of spread in
      the skin is determined by gravity, and the fluid finally localizes in the more
      dependent regions. The distance that the pneumococcic lesion travels and the
      local tissue characters have much to do with the amount of fluid that
      accumulates. Studies are also reported of some factors which alter the rate of
      spread of the edema fluid. An acceleration in rate occurs when H. influenzae is
      used as an associative infective agent with the Pneumococcus.

PMID- 19869965
TI  - STUDIES ON THE SPECIFIC CHARACTERISTICS OF SYPHILITIC BLOOD PROTEINS : I. SURFACE
      TENSION AND SOLUBILITY.
AB  - THESE EXPERIMENTS SHOW: 1. That the surface tension of normal blood serum is
      considerably lowered by standing undisturbed for a period of 1 hour (time-drop).
      2. That the greatest time-drop recorded is with serum diluted approximately
      10,000 times in fresh serum, and 50,000 times in heated serum. 3. That immune
      serum is not affected in the same manner by heat as is normal serum. Syphilitic
      serum and anti-sheep cell rabbit serum behave similarly in this respect. 4. That
      serum albumin is much more readily soluble in alkaline buffer solutions than
      globulin is, and that globulin from normal serum ionizes more than that from
      syphilitic serum. Further investigations are being made in an effort to determine
      why the proteins aggregate or dissociate under the influence of the factors under
      consideration.

PMID- 19869966
TI  - ORAL IMMUNIZATION AGAINST PNEUMOCOCCUS TYPES II AND III AND THE NORMAL VARIATION
      IN RESISTANCE TO THESE TYPES AMONG RATS.
AB  - 1. Considerable variation in the resistance of different rats toward Type II
      pneumococcus has been demonstrated. In general, older rats survive much greater
      doses than young ones, illustrating the acquisition of a natural partial
      immunity. The same is true for Type III but the immunity appears somewhat later
      in life and does not reach the same height. 2. An active immunity can be created
      against Types II and III in rats by feeding the dead organisms or the Berkefeld
      filtrate of the bile salt-dissolved cells. This immunity resembles that obtained
      against Type I in several respects.

PMID- 19869967
TI  - THE ROLE OF THE SOLUBLE SPECIFIC SUBSTANCE IN ORAL IMMUNIZATION AGAINST
      PNEUMOCOCCUS TYPE I.
AB  - 1. Feeding the purified soluble specific substance of Type I pneumococcus
      protects rats against an intraperitoneal injection of the virulent organism. 2.
      This increased resistance resembles that obtained when the intact (dead) or
      dissolved bacteria are fed, as follows: (a) one feeding is sufficient, (b) the
      interval between the feeding and the appearance of the immunity is the same, (c)
      the duration is approximately the same, (d) when the immunity is exhausted it can
      be renewed by a new feeding, (e) the immunizing action is type-specific. 3. The
      differences between the effects of feeding the purified specific substance and
      the intact or dissolved organism to rats, appear to be quantitative rather than
      qualitative, the proportion of animals protected and the height of the immunity
      being generally, though not always, less in the case of the former. 4. In
      contrast to the immunizing action which the soluble specific substance possesses
      when administered to rats, feeding it to mice failed to protect them. Neither
      were mice definitely immunized by parenteral administration. 5. A sodium
      glycocholate solution of Pneumococcus Type I lost part of its immunizing activity
      on standing for 1 year. 6. The failure to immunize mice and the loss of activity
      of the bile salt solution of pneumococcus, on standing, are discussed in terms of
      (a) the possible presence of a second cell constituent which is active by mouth,
      and (b) a possible intramolecular change in the type-specific polysaccharide
      associated with a loss of immunizing action while retaining the precipitin
      reaction.

PMID- 19869968
TI  - THE ROLE OF THE SOLUBLE SPECIFIC SUBSTANCE IN ORAL IMMUNIZATION AGAINST
      PNEUMOCOCCUS TYPES II AND III.
AB  - 1. When the soluble specific substance of Type II pneumococcus was fed to rats,
      little or no increased resistance to the organism was obtained. 2. When the
      specific substance of Type III pneumococcus was fed, an increased resistance to
      the virulent organism resulted. The percentage of animals protected is smaller
      than when the whole or the dissolved cell is fed. 3. When the specific
      polysaccharide of Type I was fed, no immunity against Type II or III was
      obtained, and the ingestion of the specific substances of Types II and III did
      not protect rats against the Type I organism.

PMID- 19869969
TI  - THE ACCUMULATION OF IRON IN TUBERCULOUS AREAS : II. SURVIVAL TIME OF TUBERCULOUS
      RABBITS INJECTED WITH FERRIC CHLORIDE.
AB  - Repeated intravenous injections of ferric chloride are followed by an increase in
      the survival time of tuberculous rabbits. In the particular series of experiments
      reported this increase amounts to about 78 per cent over the average survival
      time of control rabbits. Tuberculous animals repeatedly injected with ferric
      chloride increase in weight during part of the period of these injections. The
      level reached in the series studied markedly exceeds that attained by control
      rabbits. Both control and experimental animals die of generalized tuberculosis.
      There is no indication at the time of death of any differences in the degree of
      pathological involvement between the two groups of animals.

PMID- 19869970
TI  - THE EFFECT OF BILATERAL SUPRARENALECTOMY IN ADULT ALBINO RATS ON THE NATURAL AND
      ACQUIRED RESISTANCE TO BARTONELLA MURIS ANEMIA.
AB  - Normal adult Wistar rats (non-carrier stock) are readily infected with Bartonella
      muris and develop a severe anemia if large amounts of infecting material are
      used. The normal adult rat of Wistar stock possesses a relatively high natural
      resistance to spontaneous infection with this organism. Bilateral
      suprarenalectomy in Wistar rats lowers the natural resistance to a subsequent
      infection with Bartonella muris. This procedure does not alter the type of tissue
      response to the virus but lowers the natural resistance of the rat to toxic
      effects of the infection. The acquired immunity to Bartonella muris conferred by
      a first infection is not broken down by subsequent suprarenalectomy. The
      mechanisms of acquired and natural resistance are dependent on different
      physiological processes in the organism and are not merely quantitative
      variations of the same process as is generally assumed.

PMID- 19869971
TI  - CONDITIONS INFLUENCING THE DISAPPEARANCE OF LIVING BACTERIA FROM THE BLOOD
      STREAM.
AB  - 1. The simultaneous intravenous injection into normal and actively immunized
      rabbits of equal quantities of living staphylococci or paratyphoid bacilli is
      followed by a distinctly accelerated rate of removal of the bacteria from the
      blood streams of the immune animals. 2. This altered reactivity is due
      essentially to specific active immunization. 3. The bacteria pass rapidly through
      the capillary bed of the lungs, extracellularly and dispersed for the most part,
      and become generalized through the blood stream. 4. The bacteria are quickly
      removed from the circulating blood in the immune animals and less rapidly in the
      normal ones, by various organs, particularly the liver and spleen, where they
      accumulate in enormous numbers, become adherent to the lining membrane of the
      sinusoids of the liver and apparently to the macrophages of the spleen and are
      phagocytosed by the macrophages and leucocytes in these organs. 5. Associated
      with this effect are morphological changes in the bacteria as shown by swelling,
      loss of staining power and evidences of increased cohesiveness and decreased
      viscosity, these changes being apparent as early as 2 minutes after their
      intravenous injection. 6. Inasmuch as these changes are not seen to a marked
      degree within the lungs or other organs, they are probably the result of a local
      antigen-antibody reaction of a bacteriotropic type in the two organs generally
      considered to be most actively concerned with the production of immune bodies. 7.
      By means of this accelerated bacteriotropic effect in the actively immunized
      animals, phagocytosis is facilitated and intracellular digestion of the bacteria
      is enhanced.

PMID- 19869972
TI  - THE FATE OF ORALLY ADMINISTERED SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS TYPES
      I, II AND III.
AB  - 1. Rats, when fed the soluble specific substance of Types I, II and III
      pneumococcus, excrete a very large proportion in the feces. 2. Following
      ingestion of these substances, tests sensitive enough to detect 1 part in
      2,000,000 of serum, and 1 part in 3,000,000 of urine, were negative. 3. The
      polysaccharide of Type I, when recovered from the feces, is as active an
      immunizing agent as it was originally.

PMID- 19869973
TI  - THE INFLUENCE OF AGE AND OF DURATION OF TREATMENT ON THE PRODUCTION AND REPAIR OF
      BONE LESIONS IN EXPERIMENTAL HYPERPARATHYROIDISM.
AB  - These studies have shown that the bones of guinea pigs given daily injections of
      parathormone from the age of 2 to 7 days to the age of 110 to 120 days, show
      relatively very little effect after receiving 20 units daily during the last 65
      to 87 days of treatment. But it is probable that their bones underwent
      decalcification early in the treatment and that subsequently the parathormone,
      continued at the same dosage, did not maintain the effects on the bones. Healing
      finally occurred despite it. The bones of guinea pigs treated with intermittent
      injections of large doses of parathormone from the time they were 1 week old to
      the age of 95 to 145 days also showed relatively few changes at the end of the
      treatment. The injections were given at intervals of 7 to 11 days, and were
      stepped up from 60 units to 140 units. From our previous experience (1) we infer
      that the earlier injections of parathormone produced very extensive bone changes
      which healed in the intervals between the injections. As the guinea pigs became
      older the injections of parathormone did not produce as severe effects. We have
      found in our studies of experimental hyperparathyroidism that the bone changes
      after a single large dose of parathormone in young guinea pigs are soon healed.
      The study of a series of animals shows that healing begins at about the 48th hour
      after injection, and proceeds rapidly. Between the 8th and 14 days, callus may be
      observed at the costochondral junctions, where fractures had occurred. Now the
      endosteum may be lined by osteoblasts and the vessel canals by new formed bone.
      In adult guinea pigs extremely large single doses had little effect on the bones
      in 48 hours, even though the dose killed the animal. It was only when three doses
      pyramided over a period of 48 hours and totaling 2580 units of parathormone were
      given, that moderately severe bone resorption could be demonstrated in the adult.
      The elevation of serum calcium may be considered as one of the indices of calcium
      mobilization in experimental hyperparathyroidism. When the rate of calcium
      excretion exceeds the rate of its mobilization, or when the animal is on a low
      calcium diet, hypercalcemia may be absent. It is possible to raise the serum
      calcium of adult guinea pigs by large single doses of parathormone, but the
      resulting rise is not as great as in the young (2). This is confirmatory evidence
      of the fact that calcium is mobilized much less rapidly from the bones of old
      animals than from those of young ones. Collip pointed out that young normal dogs
      are more susceptible to parathormone (6). This observation was corroborated by
      Morgan and Garrison (7). We found that the same difference held also in
      experimental hyperparathyroidism produced in dogs by repeated doses of
      parathormone (8). In man, clinical experience likewise indicates the necessity of
      using relatively large doses of parathormone to raise the serum calcium of
      adults. The serum calcium of middle-aged or old adults does not rise
      significantly unless as much as 100 units or more of parathormone are given daily
      for a number of days. Charts VI and VII, in a recent paper by Merritt and Bauer
      (9), support our findings of the relative difficulty of obtaining a significant
      elevation of serum calcium in adults. If adult guinea pigs are given daily
      injections of parathormone which are rapidly stepped up, the animals may be
      killed by the ensuing acute hyperparathyroidism, only slight bone changes being
      produced. However, a careful avoidance of the induction of acute
      hyperparathyroidism by gradual stepping up of the parathormone dose permits the
      employment of doses continued over a long period of time that could not possibly
      have been tolerated otherwise. Furthermore, healing of the lesions thus produced
      may occur, in spite of the continuance of parathormone at this level. It seems
      likely that the difference in response of young and old guinea pigs to single
      doses of parathormone, as indicated by the bone changes, as well as by the serum
      calcium and phosphorus, is related to the more rapid rate of mineral metabolism
      in the young, actively growing animals. The calcium mobilizing effect of
      parathormone is most prominent in actively growing young animals, the calcium
      being withdrawn from the most readily available stores-the regions of most active
      new bone formation and most active bone reconstruction (10). In the adult animal
      the calcium reserves (in the formed bone) are less susceptible to the calcium
      mobilizing effect of parathormone. The adult guinea pig will show relatively
      slight bone changes even as a result of extremely large, fatal doses of
      parathormone. Repeated doses, as is well known, will produce, by pyramiding,
      greater effects than the entire amount administered at one time. In this type of
      experiment the young again show greater susceptibility of the bone than the
      adult. In time, however, some compensation takes place, and the effects of the
      same doses are decreased until finally healing may occur in spite of the
      continued treatment. Increase of the dose, however, again elicits the
      parathormone effects upon the bone, as well as upon the serum calcium and
      phosphorus, without toxic changes (1, 8). It would seem that some compensation
      sets in which may be overcome by increasing the dose. This compensation is
      especially evident in the experiments in which the parathormone doses were
      stepped up gradually from small amounts. In addition to the compensation observed
      in young and adult animals as a result of repeated injections of parathormone, we
      must also consider the possibility that there is a compensating mechanism in
      adult animals more effective than in the young. That compensation occurs is
      unquestionable but its nature is not clear. Apparently it is less effective
      during pregnancy, doses of parathormone which produce only slight bone changes in
      ordinary adults causing very severe lesions in advanced pregnancy (11).
      Parathormone has been shown to produce only one primary effect on bone, and that
      is decalcification. This may come about as the result of a change in the
      circulating tissue fluids, the salts being dissolved out of the organic matrix,
      and the latter disappearing secondarily. The process is most rapid in the
      vicinity of most active bone formation. The osteoblasts disappear from the
      surfaces of bone where dissolution is occurring, and at the same time the marrow
      connective tissue proliferates. Fusion of cells produces osteoclasts (12), which
      then proceed to remove the decalcified organic matrix, with the production of the
      deep lacunae of Howship. Frequently leucocytes are also observed actively
      phagocyting the decalcified organic matrix, and often leucocytes are observed
      within the osteoclasts (12). Healing is associated with the complete reversal of
      the process. The osteoclasts disappear, the connective tissue diminishes,
      osteoblasts reappear, and bone formation is resumed. As we have previously stated
      (13), parathormone produces a more continuous effect than experimental acidosis
      and greater changes than are seen in experimental osteoporosis. A pronounced
      decalcification results from it which, with its sequelae, simulates von
      Recklinghausen's disease. The emphasis which the older pathologists laid on
      osteoclasts as a special feature of ostitis fibrosa cystica is justified, for in
      the experimental condition the appearance of great numbers of osteoclasts is a
      constant feature, whenever decalcification occurs (13). There seems to be no
      doubt that the giant cell tumors found in ostitis fibrosa cystica are expressions
      of the same pathological response. The other features of the bone changes of
      hyperparathyroidism-marrow hemorrhage, cysts, fractures, and osteoid
      proliferation-are secondary to the primary decalcification. Progress of the
      pathological changes leads to circulatory stasis and cyst formation. Stresses and
      strains exerted on the progressively weakening bone may result in microscopical
      or gross fractures. Osteoid tissue is, as we have previously pointed out (13),
      merely reparative in nature, being laid down as support to the weakened or
      fractured bone, or as a part of healing. Osteoid borders appear on bone surfaces
      48 hours after one large dose of parathormone. The mosaic picture which we have
      observed in the bones of some of our animals is produced by short and irregularly
      disposed cement lines resulting from rapid bone transformation. Schmorl (14)
      recently emphasized the mosaic-like appearance of the newly formed lamellar bone
      in Paget's disease (ostitis fibrosa deformans). The mosaic-like appearance of
      bone has also been described in local bone conditions, as e.g. syphilitic
      periostitis, and in bone in the vicinity of cysts and giant cell tumors in von
      Recklinghausen's disease (ostitis fibrosa cystica). However, Schmorl claims that
      in no disease is the mosaic appearance so constant and the arrangement of the
      cement lines so irregular as in Paget's disease. In chronic experimental
      hyperparathyroidism (von Recklinghausen's disease), the mosaic structure is not a
      prominent feature because of the progressive decalcification. But the bones of
      our young guinea pigs which received intermittent injections showed a mosaic-like
      appearance indicative of the periodic decalcifications and restorations which
      they had undergone.

PMID- 19869974
TI  - THE ARTHUS PHENOMENON : LOCAL ANAPHYLACTIC INFLAMMATION IN THE RABBIT
      PERICARDIUM, HEART, AND AORTA.
AB  - An intense inflammatory reaction in the pericardium, heart, and intrapericardial
      aorta can regularly be produced in a sensitized rabbit by the intrapericardial
      injection of the homologous antigen.

PMID- 19869975
TI  - THE ARTHUS PHENOMENON : LOCAL ANAPHYLACTIC INFLAMMATION IN THE RABBIT BRAIN.
AB  - 1. Sixteen out of seventeen rabbits actively sensitized to various antigens by
      repeated cerebral and intravenous injections showed upon intracerebral
      reinjection of the same antigen local anaphylactic inflammation of the brain at
      the site of inoculation. 2. Six out of twenty rabbits actively sensitized to
      either horse serum or egg albumen by extracerebral injections, showed, upon
      introduction of the homologous antigen into the cerebrum, local anaphylactic
      inflammation at the site of inoculation. 3. The pathological picture of the
      Arthus phenomenon in the brain of the rabbit resembled that seen in the skin,
      after allowing for differences in the fundamental structure of the tissues
      involved. 4. None of the control animals exhibited lesions comparable to those
      found in the experimental animals. A few controls showed slight hemorrhages due
      to mechanical injury of blood vessels. 5. Clinical symptoms of varying degrees of
      severity, often leading to the death of the rabbit were observed in the
      sensitized animals. These symptoms were referable to the site of injection.

PMID- 19869976
TI  - UREA TOLERANCE AFTER UNILATERAL NEPHRECTOMY IN RABBITS.
AB  - The method of study has an objective somewhat different from, and lacking the
      precision of, the ratio of Addis and the urea clearance of Van Slyke. It serves,
      however, to demonstrate that although for a month after unilateral nephrectomy
      the remaining kidney shows diminished capacity to hold blood urea within the
      normal range, nevertheless after 4 months this function is maintained in
      essentially the same degree as if both kidneys were present. This does not imply
      that all activities of the kidney remaining after unilateral nephrectomy are
      potentially augmented, but the data offered justify the conclusion that as the
      remaining kidney undergoes enlargement its functional capacity increases and the
      process represents a genuine hypertrophy in the critical sense.

PMID- 19869977
TI  - THE CORRELATION BETWEEN THE HISTOLOGICAL CHANGES AND THE FATE OF LIVING TUBERCLE
      BACILLI IN THE ORGANS OF TUBERCULOUS RABBITS.
AB  - It has been found that although there is some parallelism between the quantity of
      tubercle bacilli demonstrable histologically and the number of colonies that can
      be isolated from a given tissue, the culture method is far the more efficient in
      indicating quantitative relations. Tubercle bacilli were not perceived in the
      organs of rabbits 1 day after infection with the modified BCG although as many as
      1,500 colonies were isolated from one of them. This may be solely because it is
      difficult to see widely dispersed single minute acid-fast rods in the diffuse
      infiltrations of mononuclears with their hyperchromatic nuclei and sparse
      cytoplasm. Later, with the formation of tubercle, the parallelism is much closer.
      The culture method gives evidence concerning the number of living tubercle
      bacilli in the tissue. The significance of the accumulation of acid-fast
      particles in the tissues has been discussed. It has been seen that from the
      beginning this accumulation is greater in the Kupffer cells of the liver, in the
      macrophages of the spleen and in the reticular cells of the bone marrow than
      within the mononuclears of the lung, the organ where the bacilli grow with the
      greatest rapidity and are destroyed with the greatest difficulty. Acid-fast
      particles are more prominent with the bovine than with the human bacillus or the
      BCG, the microorganism that is destroyed with the greatest difficulty thus
      leaving more incompletely digested bacillary debris at a given time within the
      cells. Thus it seems permissible to conclude from the presence of acid-fast
      material that some tubercle bacilli are undergoing destruction even 24 hours
      after infection. The initial accumulation of polynuclear leucocytes corresponds
      with the subsequent severity of the infection. Despite the greater primary
      localization of bacilli in the liver, this initial inflammatory reaction with all
      three infections is much greater in the lung than in the liver. In each organ it
      is more intense with the bovine than with the less virulent strains. The
      multiplication of the bacillus and its accumulation within large mononuclear and
      young epithelioid cells is accompanied by an intense formation of new
      mononuclears by mitosis. The more rapid the growth of the bacillus, the more
      conspicuous the regeneration of these cells. Thus with all strains mitosis is
      more intense in the more susceptible organ, as in the lung compared with the
      liver; with the most virulent strain the most extensive and diffuse accumulation
      of these new cells corresponds with the greater rise in the numbers of bovine
      bacilli after the lag of the 1st week. With the maturation of the epithelioid
      cells and the formation of tubercles the bacilli have already been greatly
      reduced numerically and the speed of this process diminishes with the virulence
      of the three strains used. The faster the development of tubercle the faster the
      destruction of the bacillus and the earlier the resorption of the tubercle.
      Tubercle bacilli never accumulate in such large numbers in the mononuclears of
      the liver as they do in the lung. Though at first the tubercles in the liver may
      be more numerous than those in the lung they never attain the same size. The
      formation of new mononuclears by mitosis is restricted and Langhans' giant cells
      appear very early (1st and 2nd weeks). In the lung, giant cells are not found
      until much later with the BCG and the human bacillus (4th week); they were not
      noted in the interstitial tubercles with the bovine type, but the extension of
      these tubercles was accompanied by an unabated mitosis of mononuclears until the
      death of the animal. The liver tubercles are resorbed early even with the bovine
      infection. Associated with these histological differences are the slow initial
      growth and the early and complete destruction of the tubercle bacilli even of
      bovine type in the liver, and the more rapid initial growth in the lung, with the
      later destruction of the BCG and the human bacillus and the unabated growth of
      the bovine bacillus. Similar differences were observed between the splenic pulp
      and corpuscle. In the former the accumulation of acid-fast particles was much
      greater and the tubercles developed earlier. Mitosis of mononuclears was less
      frequent and giant cells appeared earlier. Tubercle bacilli, always
      intracellular, disappeared from the tubercles in the pulp sooner than from those
      in the corpuscle, and the tubercles themselves first disappeared from the pulp.
      Consequently with the persistence of bacilli mitosis continued in the tubercles
      of the corpuscle and these attained a much larger size. Moreover individual
      resistance is linked with the ability to form mature tubercles early. In two
      animals simultaneously infected with the same strain and killed at the same time,
      the destruction or retardation of the bacillus is greater in that rabbit in which
      maturation of the tubercle and of epithelioid cells has proceeded further (Figs.
      15 and 16). These observations indicate that the mononuclears of different organs
      or even of the same organ, as in the different parts of the spleen, have a
      different capacity to destroy the tubercle bacillus, and that the transformation
      of the mononuclear into the mature epithelioid cell follows its destruction of
      the tubercle bacilli. In the lung the more virulent types of bacillus are
      destroyed within the epithelioid cells of interstitial tubercles but persist in
      foci of tuberculous pneumonia. In this organ in rabbits infected with the human
      strain and to a lesser degree in rabbits infected with the bovine strain, the
      parasite largely disappears from the epithelioid cells of interstitial tubercles.
      But with both strains tubercle bacilli in large numbers may accumulate within
      epithelioid cells lying free in the alveoli. With the human type they are
      numerous within the cells and free in caseous material in the localized foci of
      caseous pneumonia. With the bovine infection, this caseous pneumonia is more
      often widespread and in the areas of caseous pneumonia the greater part of the
      vast accumulation of bovine bacilli in the lungs is found; as many as 200,000
      colonies have been isolated from 10 mg. of tissue (Fig. 11). Flooding of the
      respiratory passages by the caseation of tuberculous lesions into the bronchi
      plays an important role in dissemination of tubercle bacilli through the lung.
      The process on the contrary is predominantly interstitial when the bovine
      bacillus is held in check (Fig. 12). Thus there is apparently some factor acting
      in the alveoli that favors the growth of the parasite. The accumulation of
      tubercle bacilli is seen especially in the peripheral epithelioid cells in
      immediate contact with the alveolar space. In the same lung the bacilli are much
      fewer in the interstitial tubercles. The accumulation in human tuberculosis of
      large numbers of tubercle bacilli in the tissues lining cavities is well known.
      Novy and Soule (20) have shown that within certain limits the growth of the
      bacillus in vitro is proportional to the oxygen tension of its environment.
      Corper, Lurie and Uyei (21) have confirmed these observations and have noted
      further that a difference in the gaseous environment of the bacilli equal to the
      difference between the conditions existing in the alveolar air and the venous
      blood is sufficient to cause a considerable increase in the growth of the
      microorganism in vitro. Loebel, Shorr and Richardson (22) by the use of Warburg's
      manometer have found that the oxygen consumption of tuberculous tissue is such
      that a tubercle 0.5 mm. thick would completely exhaust the oxygen of the air
      before it reached the center. These observations suggest that a factor
      responsible for the greater multiplication of the bacillus in the cells of the
      alveoli may be the greater oxygen tension of the alveolar air. In the liver,
      spleen and bone marrow even with the bovine infection many instances were found
      of the effective destruction of the parasite synchronously with the maturation of
      epithelioid cells and the formation of tubercle. On the other hand, in the spleen
      and bone marrow of some rabbits, living bacilli persisted within the epithelioid
      cells of isolated tubercles even 2 months after infection, a condition never
      found with the human type or BCG infection. Thus the epithelioid cell is the
      means of defense for the rabbit against the bovine type bacillus, and as such it
      is usually adequate in the liver, spleen and bone marrow though ineffective in
      the lung and kidney. In the latter, descending infection, and the occasional
      colony-like multiplication of bacilli in unorganized material, tubular casts,
      determine the long persistence of large numbers of bacilli in this organ. In
      differentiating the mononuclear phagocyte of the connective tissues into the
      monocyte and clasmatocyte Sabin and her coworkers (23) have maintained that the
      clasmatocyte can efficiently destroy the tubercle bacillus but that the monocyte
      and its derivatives, the epithelioid and Langhans' giant cells, cannot. With the
      progress of the disease they have noted that the monocytes accumulate in great
      numbers in the foci of infection and overflow into general circulation (4). White
      (24) and Sabin and her coworkers have concluded that tuberculosis is specifically
      a disease of the monocyte, and that this cell and its derivatives act as
      incubators for the tubercle bacillus. Doan and Sabin (25) have therefore sought,
      with indecisive results, to protect the body against tuberculosis by an
      antimonocytic serum. However it has been shown here that although an intense
      multiplication of mononuclears is associated with the growth of the tubercle
      bacillus, their transformation into mature epithelioid cells is constantly
      associated with its destruction, and the rapidity of the destruction varies with
      the rapidity of the maturation of tubercle. (ABSTRACT TRUNCATED)

PMID- 19869978
TI  - THE IDENTITY OF THE MECHANISMS OF TYPE-SPECIFIC AGGLUTININ AND PRECIPITIN
      REACTIONS WITH PNEUMOCOCCUS.
AB  - THE EXPERIMENTAL RESULTS WHICH HAVE BEEN DESCRIBED DEMONSTRATE THE FOLLOWING
      FACTS: 1. In the type-specific agglutination reaction, when the organisms are not
      present in sufficient numbers to absorb completely all the antibodies from the
      serum, more antibody is bound by cellular S than is required for the process of
      agglutination. 2. The excess of antibody thus bound can then unite with
      additional amounts of the specific substance when this is added in soluble form
      to the agglutinated material. 3. If an excess of the free S is added to an
      agglutinated mass of antibody and bacteria, the organisms are redispersed and in
      the suspended state are again specifically agglutinable. 4. When a solution of
      the specific polysaccharide is added in excess to an homologous immune serum, a
      prozone is created in which precipitation is inhibited; moreover, if, at this
      point, type-specific pneumococci are added to the mixture, inhibition of
      agglutination also occurs. 5. The reactive substance in the type-specific
      agglutination and precipitation reactions is the same, i.e., the capsular
      polysaccharide. In the former instance it is combined in the bacterial cell; in
      the latter, it is in a soluble, chemically purified state and entirely separate
      from the body of the cell.

PMID- 19869979
TI  - PROTECTION OF ADRENALECTOMIZED ANIMALS AGAINST BACTERIAL INTOXICATION BY AN
      EXTRACT OF THE ADRENAL CORTEX.
AB  - 1. The resistance of adrenal-deficient rats to bacterial intoxication has been
      significantly increased by an extract of the adrenal cortex. 2. This is shown
      both for acute intoxication with killed Bacillus typhosus and for chronic
      intoxication with killed Staphylococcus aureus. 3. During the height of the
      bacterial intoxication relatively large amounts of the cortical hormone are
      apparently required to maintain the animals. 4. It is considered probable that a
      human pyogenic infection imposes a severe load upon the adrenal cortex.

PMID- 19869980
TI  - THE EPIDEMIOLOGY OF FOWL CHOLERA : VI. THE SPREAD OF EPIDEMIC AND ENDEMIC STRAINS
      OF PASTEURELLA AVICIDA IN LABORATORY POPULATIONS OF NORMAL FOWL.
AB  - 1. Strains of-P. avicida from "spontaneous epidemics" of fowl cholera, when
      introduced intranasally in fixed doses into specially bred chickens, induced
      fatal fowl cholera in about 40 per cent but did not survive in the nasal clefts
      of resistant birds nor spread to normal contacts. 2. Strains of P. avicida from
      "spontaneous endemics" of fowl cholera, when introduced similarly into chickens,
      failed to kill but did survive in the nasal clefts of inoculated birds and spread
      readily to normal contacts. 3. "Laboratory" variants of the epidemic strains of
      P. avicida failed to kill or survive in the test birds and did not spread to
      contacts.

PMID- 19869981
TI  - SERUM SICKNESS IN RABBITS : II. PRECIPITINOGEN AND PRECIPITINS IN RELATION TO
      APPEARANCE OF THE REACTION.
AB  - 1. It has not been possible to demonstrate in rabbits affected with serum
      sickness any constant temporal relationship between precipitin and precipitinogen
      in the blood on one hand and of occurrence of serum sickness on the other hand.
      2. It has not been possible to demonstrate any differences between the precipitin
      and precipitinogen curves in injected rabbits which develop serum sickness
      compared with injected rabbits which did not develop serum sickness. 3. There is
      therefore no evidence that we can directly associate the occurrence of serum
      sickness with the production or appearance of precipitins.

PMID- 19869982
TI  - THE TRANSFORMATION IN VITRO OF R PNEUMOCOCCI INTO S FORMS OF DIFFERENT SPECIFIC
      TYPES BY THE USE OF FILTERED PNEUMOCOCCUS EXTRACTS.
AB  - 1. Avirulent R pneumococci derived from S forms of a specific type may be changed
      by growth in broth containing anti-R serum and a heated, filtered extract of S
      pneumococci of a different type, into virulent S organisms identical in type with
      the bacteria extracted. This has been accomplished in the case of R strains
      derived from Type II pneumococci, employing extracts prepared from Type III and
      Type I S forms. 2. The constituents of the extract supply an activating stimulus
      of a specific nature in that the R pneumococci acquire the capacity of
      elaborating the capsular material peculiar to the organisms extracted.

PMID- 19869983
TI  - IMMUNOLOGICAL REACTIONS OF PNEUMONIC PLEURAL FLUIDS.
AB  - Pleuritic exudates from patients with lobar pneumonia may be sterile or infected.
      Sterile fluids, at or about the time of crisis, contain actively acquired
      antibodies similar to those in the blood serum. Infected fluids do not contain
      such antibodies, presumably because of the presence in them of large amounts of
      soluble specific substance. Sterile fluids from patients treated with immune sera
      have both horse serum and antibodies similar to those injected. Infected fluids
      from serum-treated cases contain horse serum and such heterologous antibodies as
      were contained in the therapeutic sera together with homologous soluble specific
      substance. The concentration of horse serum and antibodies in pneumonic fluids is
      usually the same or somewhat less than that of the corresponding blood sera.

PMID- 19869984
TI  - TOXIN-ANTITOXIN REACTION WITHOUT NEUTRALIZATION.
AB  - 1. Collodion particles adsorb diphtheria or tetanus or botulinus toxins. These
      toxins are retained on the particles when washed but are at least in part
      released in the animal. 2. The adsorbed toxins are neutralized by adsorption of
      the corresponding antitoxins but are unaffected by other serums. 3. When
      collodion particles are treated first with tetanus antitoxin, then with
      diphtheria toxin, they are not toxic, but they become toxic when they are treated
      first with diphtheria antitoxin, then with the diphtheria toxin. Similarly when
      collodion particles are treated first with diphtheria antitoxin and then with
      tetanus toxin, they do not become toxic, but they become toxic when they are
      treated with tetanus antitoxin and tetanus toxin.

PMID- 19869985
TI  - A NOTE ON THE SPECIFIC AGGLUTINATION OF PNEUMOCOCCUS TYPES I, II AND III.
AB  - 1. Type-specific agglutination of Pneumococcus Types I, II and III has been
      demonstrated in antisera largely deprived of the carbohydrate antibody. 2. The
      type-specific agglutinogens in Pneumococcus I and II responsible for
      agglutination in such antisera are inactivated by heating in alkaline solution at
      100 degrees C. The specific carbohydrate remains unaltered under these
      conditions. 3. The relationship of the type-specific agglutinogen in
      Pneurmococcus I to the type-specific A substance has been discussed. 4. The
      possible application of these results to the standardization of therapeutic
      antisera by agglutinin titre has been discussed. 5. On the basis of the
      experiments recorded a tentative explanation is offered for the failure of
      Pneumococcus Type II to absorb the agglutinins from anti-B. friedlaenderi Type B
      serum.

PMID- 19869986
TI  - THE RELATION OF HYDROSTATIC PRESSURE TO THE GRADIENT OF CAPILLARY PERMEABILITY.
AB  - The gradient of permeability along the capillaries of voluntary muscle and the
      capillaries and venules of skin exists independently of the hydrostatic
      conditions, though influenced by them. Its presence cannot be explained by a
      graded tonic contraction of the capillaries. The evidence,-like that of previous
      papers,-points to local differences in the barrier offered by the wall of these
      vessels as responsible for the gradient.

PMID- 19869987
TI  - STUDIES ON INFLUENZAL MENINGITIS : I. THE PROBLEMS OF SPECIFIC THERAPY.
AB  - 1. An acute purulent meningitis due to the invasion of the meninges by Pfeiffer's
      influenza bacillus is not a very uncommon disease ininfants and young children.
      It has a very high mortality. 2. Complement is entirely absent in the
      cerebrospinal fluid of these cases, and bactericidal experiments suggest that the
      injection of a specific antiserum will have but slight lethal effect on the
      organisms unless complement is injected at the same time. 3. Treatment with a
      mixture of specific antiserum and complement led in some cases to a definite
      clinical improvement, coincident with sterilization and clearing of the
      cerebrospinal fluid. But after some days, the patients relapsed and died. Autopsy
      showed localized abscesses in the vicinity of the base of the brain, the lesions
      being definitely walled off from the general subarachnoid space. In one case, the
      patient recovered. 4. Since the walls of the abscesses apparently present an
      insuperable mechanical obstacle to the action of the antiserum and complement,
      the possibility of preventing the formation of abscesses is discussed. Earlier
      diagnosis and more rapid sterilization are the most obvious measures.
      Bactericidal experiments indicate that the proportion of antiserum to complement
      may be an important factor in bringing about a more rapid elimination of the
      bacilli.

PMID- 19869988
TI  - STUDIES ON INFLUENZAL MENINGITIS : II. B. INFLUENZAE-THE PROBLEM OF VIRULENCE AND
      RESISTANCE.
AB  - 1. By a suitable bactericidal technique, it can be demonstrated that the virulent
      S influenza bacillus is completely resistant to the bactericidal action of
      diluted normal unheated serum. In contrast, the R organism is easily killed when
      subjected to the action of diluted normal serum. Although this is not a true
      virulence test, it promises to be a useful substitute when a susceptible animal
      is not available. 2. The S culture filtrate contains a substance with a strong
      antibactericidal effect, but the R culture filtrate does not contain this
      substance. 3. It would appear probable that this antibactericidal substance is
      identical with, or closely related to the precipitinogen (or soluble substance)
      which is present only in the culture fluid of the S influenza bacillus. In view,
      however, of differences in heat stability of the two substances, this question
      must remain in doubt until a supply of purified precipitinogen is available. 4.
      Quantitative agglutination, precipitation and bactericidal comparisons between
      (a) R-absorbed anti-S serum and unabsorbed anti-S serum and (b) anti-S serum and
      anti-R serum indicate that the agglutinogen is a separate antigen, and the
      agglutinin a separate antibody, taking no part in the bactericidal action of the
      antiserum. They also indicate that the precipitin, which is present only in the
      anti-S serum, is identical with the bactericidal antibody. 5. The relation of the
      precipitinogen (or soluble substance) to virulence and of the precipitin to
      resistance is discussed.

PMID- 19869989
TI  - THE INCIDENCE OF CANCER IN TARRED AND SHELTERED MICE.
AB  - Mice sheltered for long periods from the intercurrent access of living entities
      out of the environment developed tar cancer with the same frequency as controls
      exposed to an unusual extent. This happened although the food of the two groups
      differed profoundly in character.

PMID- 19869990
TI  - ANTIGENIC STREPTOCOCCAL HEMOLYSIN.
AB  - 1. Normal serum, used in cultures for preparation of the streptolysin, modifies
      the properties of the streptolysin, causing delayed hemolysis, increased
      filterability, resistance to oxidation or reduction, and absence of antigenicity.
      1. Streptolysin prepared without serum is an active antigen. 3. Similar
      temperatures are required to destroy the antigenic activity of serum-free
      streptolysin and the skin reactivity of Dick toxin. 4. Scarlet fever antitoxin
      contains antistreptolysin which does not neutralise serum streptolysin and which
      can be detected only by titration against serum-free streptolysin. 5. The
      antihemolysin which neutralises serum-free streptolysin is species-specific but
      not type-specific.

PMID- 19869991
TI  - ON THE NUTRITIONAL REQUIREMENTS IN VITRO OF NORMAL AND MALIGNANT MOUSE
      EPITHELIUMS.
AB  - The cultivation in vitro of mouse tissues derived from normal organs from 86
      spontaneous epithelial tumors of the mammary gland, and from 27 Ehrlich
      carcinomas, has been undertaken, together with a study of the properties of the
      various cell types. 1. The tissues liquefied fibrin from mouse and rat plasma
      more readily than fibrin from chicken plasma. Clots made of chicken plasma alone,
      if thoroughly washed, did not inhibit the migration of the cells. Normal and
      tumor tissues liquefied fibrin from the mouse, rat, and chicken more actively
      than Ehrlich carcinoma did. 2. Mouse epitheliums, both normal and malignant,
      showed greater activity than connective tissue cells from the same origin and
      were not overgrown by the latter. 3. Mouse epithelium was more active in rat
      serum than in mouse or chicken serum and in embryonic juice from chickens, mice,
      and rats. None of these fluids, however, supported cell proliferation
      indefinitely except in the case of Ehrlich carcinoma. 4. These results indicate
      that mouse tissues possess nutritional requirements which are different from
      those of fibroblasts and epithelial cells of other animals. Nutritive media that
      suffice for prolonged cultivation of the normal and malignant tissues of the rat
      and the fowl, and also of Ehrlich carcinoma, are not suitable for the cultivation
      of adult mouse epithelium derived from normal organs or from spontaneous mammary
      gland tumors. 5. Rat serum supported the life of spontaneous tumors for a limited
      period of time only, whereas it enabled the Ehrlich carcinoma to proliferate
      indefinitely. Normal organs and spontaneous tumors were not capable of invading
      normal tissues as Ehrlich carcinoma did.

PMID- 19869992
TI  - EXPERIMENTAL NEPHRITIS IN THE FROG : IV. THE SIGNIFICANCE OF THE FUNCTIONAL
      RESPONSE TO VASCULAR AND TO PARENCHYMAL DISTURBANCES IN THE KIDNEY.
AB  - A summary of our findings is briefly made. A functional examination of the
      kidneys did not allow any differentiation between the results of vascular and
      parenchymal damage. This was true, as is emphasized in the arrangement of Charts
      1 and 2, in the case of both glomerular and tubular dysfunction for it is seen
      that the type of functional derangement is identical in the two types of damage.
      Anatomical examination of the kidneys on the other hand showed definite
      differences in the state of the kidneys in the two types of damage, whether the
      dysfunction was glomerular or tubular. Certain points should be emphasized here.
      First, the validity of these results is not dependent on any particular
      interpretation of the significance of the functional phenomena observed. Whatever
      the anatomical relations between the two circulations in the kidney, whether
      urea, salts, dyes or water is excreted by one mechanism or another, no matter
      what part "filtration" or "absorption" may play in the elaboration of the final
      urine, the fact remains that the status of the function of these kidneys was
      identical, no matter how its functional state came into being, when an anatomical
      examination showed their actual condition to be significantly different. The fact
      that vascular disturbances, if of sufficient duration may in turn produce
      parenchymal changes complicates the problem still further, for in lesions that
      spontaneously develop in the kidney the mixture of vascular and parenchymal
      disturbances is so intimate that the functional results become infinitely more
      difficult of interpretation. Our previous studies have shown that even in the
      controlled extravital experiment conditions and relations of functional and
      structural response may thus become exceedingly complex (2). These complications
      were purposely avoided in the present study, however, by making the period of
      vascular disturbance short. Also, and again for the purpose of simplification,
      the toxic agent which caused the parenchymal disturbances was used in low enough
      concentration to produce only the less complex of the structural alterations that
      may follow its contact with the cells. And for the same reasons the simplicity of
      the general conditions existing in the perfusion experiments deserves special
      emphasis. Every element of the circulating fluid that is going to the kidneys is
      known and may be varied at will. Every constituent of the urine formed from this
      fluid can be accurately determined and compared with its condition in the
      circulating fluid. We have given in our experiments only rates of excretion but
      "concentration factors," "ratios," "clearances" or any other formulae might be
      calculated, without altering the conclusion that the functional status of the
      organs in the two types of damage, vascular and parenchymal, was identical. All
      these contrasts between the simplicity of our experiments and the complexity that
      must obtain when the problem is investigated in the living animal, particularly
      if mammals are used whose renal activity is only partially understood, add
      considerable weight to the conclusion that functional examination is unable to
      differentiate between two types of damage of very different significance, the one
      vascular, transient and reversible, the other parenchymal, permanent and, as far
      as the cells involved are concerned, irreparable. It might seem that a similar
      result is the proper conclusion to be drawn from the long series of similar
      attempts by clinical and experimental study to determine the condition of the
      kidneys from functional examinations. But it has been and apparently still is
      hoped, perhaps because in such examinations relations are so complex and involved
      that nothing seems beyond hope, that some refinement in method or the use of some
      selectively excreted substance, such as a dye or other foreign substance, may
      distinguish between the two conditions of vascular and parenchymal disturbance.
      The answer of our experiments is that the apparent similarity in the findings of
      the functional tests in the two cases is in fact an identity in the functional
      state in the two conditions though produced by different mechanisms; and there
      remains no reason to suppose that any procedure could distinguish between
      differences that in fact do not exist. The observation of the anatomical changes
      in the kidneys of our experiments allowed on the other hand a ready determination
      of the significance of the alteration that existed in the two conditions of
      damage, since the fate of the organ could be predicted directly from the
      structural alterations observed. In our experiments the observations were made by
      histological means; other methods which have been shown by postmortem
      pathological evidence to be valid and to give similar information, are however
      available (7). A final point in these experiments may be emphasized, well known
      perhaps, but often insufficiently appreciated, namely, a weakness in the
      anatomical approach to the problem. The morphologist is unable to describe even
      roughly the functional state of a kidney from its histological appearance. In
      certain cases of frank damage he may hazard a precarious guess, but severe
      functional disturbances may exist without any trace of structural derangement
      that can be seen by the eye. For all we know the converse may be true. And if
      such is the case in the simple and controlled conditions of our experiments, how
      can one venture to speculate on the significance or functional effects of
      inflamed glomeruli, abnormal tubules and sclerosed vessels as explaining some
      complicated clinical observation, the exact physiological basis of which is
      indeed unknown? Until the fundamental correlation of the two aspects of damage,
      functional derangement and structural change, has been made the whole problem of
      the abnormal kidney must remain not only unsolved but unsolvable.

PMID- 19869993
TI  - THE MULTIPLICATION OF THE VIRUS OF MEXICAN TYPHUS FEVER IN FLEAS.
AB  - THE VIRUS OF MEXICAN TYPHUS HAS BEEN SHOWN TO MULTIPLY ABUNDANTLY IN THE
      FOLLOWING SPECIES OF FLEAS: Xenopsylla cheopis, Ceratophyllus fasciatus,
      Leptopsylla musculi, Ctenocephalus canis, Ctenocephalus felis. In all fleas,
      Rickettsia prowazeki was demonstrated within the epithelial cells of the stomach
      and within the cells of the Malpighian tubules. Whereas in infected lice enormous
      numbers of these organisms are discharged from the disintegrating cells into the
      intestinal content, only few Rickettsiae are found in the lumen of the fleas'
      intestines. They are held back by the peritrophic membrane, which covers the
      mucosa of the entire stomach. Rickettsiae seem to enter the lumen of the gut
      almost exclusively by the route of the Malpighian tubules. Observations were made
      which seem to indicate that the fleas recover from the infection and that they
      are able to regenerate the partly destroyed intestinal mucosa. An explanation is
      given for the relative harmlessness of fleas as vectors of typhus.

PMID- 19869994
TI  - CARBOHYDRATES ADSORBED ON COLLOIDS AS ANTIGENS.
AB  - Evidence is here given that polysaccharides can be rendered antigenic by
      haptogenic adsorption upon a colloid carrier. The polysaccharides studied were
      those of B. anthracis, the meningococcus, Streptococcus viridans (Bargen), B.
      proteus, S. morgani, B. dysenteriae, both the Shiga and Hiss types, and the
      pneumococci. With the polysaccharide of Type III pneumococci, we have been unable
      in 6 weeks to produce any detectable protective antibodies, but we were able to
      produce anticarbohydrate antibodies. All the bacterial carbohydrates were non
      antigenic alone when used in the doses indicated, though containing some
      nitrogen. Dextran, which was free from nitrogen was also rendered antigenic by
      the adsorption method.

PMID- 19869995
TI  - IMMUNOLOGICAL REACTIONS BETWEEN DEXTRAN POLYSACCHARIDE AND SOME BACTERIAL
      ANTISERA.
AB  - Dextran, the synthetic polysaccharide produced by Leuconostoc mesenterioides from
      saccharose, reacts immunologically with antisera from pneumococci, some of the
      Sahnonella and some of the types of Streptococcus viridans (Bargen). This
      immunological relationship is independent of the specific antipolysaccharide
      antibodies of these sera, suggesting the existence of a distinct antibody
      produced by an active group of the specific bacterial polysaccharide, which is
      similar or identical to the active group of the dextran polysaccharide.

PMID- 19869996
TI  - DETERMINATION OF LUNG VOLUME BY RESPIRATION OF OXYGEN WITHOUT FORCED BREATHING.
AB  - A method is described for estimating the volume of air in the lungs by the
      familiar principle of mixing this air with a measured volume of oxygen, and
      determining the extent to which the nitrogen of the pulmonary air is diluted. By
      employing a scrubber to remove carbon dioxide, and by measuring the volume of gas
      in the extrapulmonary part of the system at the end instead of the beginning of
      the respiratory period, it is possible to prolong the period to as many minutes
      as are necessary for complete mixture of the gases, and thereby to carry out the
      estimation without forced breathing. The determination can be carried out with
      the Roth-Benedict or Krogh spirometer, or, more economically, with the simple
      spirometer, shown in Fig. 1, assembled from ordinary laboratory equipment. The
      method gives the same results as the hydrogen method of Van Slyke and Binger (3),
      and obviates the use and analysis of hydrogen. The relative advantages of the two
      methods are discussed above. Dr. Ronald V. Christie has informed us that he has
      encountered considerable differences in the N(2) content of the pulmonary air of
      different individuals. A gain in accuracy would therefore be made if this value
      were determined for each subject, and substituted for 79.1 in the calculation
      formulae.

PMID- 19869997
TI  - FACTORS AFFECTING THE YIELD OF SPECIFIC ENZYME IN CULTURES OF THE BACILLUS
      DECOMPOSING THE CAPSULAR POLYSACCHARIDE OF TYPE III PNEUMOCOCCUS.
AB  - All improved method is described for the preparation, concentration, and
      purification of a bacterial enzyme capable of decomposing the capsular
      polysaccharide of Type III Pneumococcus. The cultural conditions for the growth
      of the specific microorganism must be such that the capsular polysaccharide is
      completely decomposed before any appreciable amount of free enzyme is released
      into the medium. This reduces to a minimum the decomposition of the specific
      substrate by the free enzyme. As a result, a larger part of the specific
      substance remains as a source of energy for the growing microorganism and less
      enzyme is lost through inactivation during the course of decomposition of the
      specific substrate. A marked stimulation of growth and of enzyme production
      occurs when small amounts of yeast extract are added to the medium and when the
      cultures are incubated under conditions of increased aeration. Special emphasis
      is placed upon the fact that, thus far, appreciable amounts of the specific
      enzyme have been obtained only when the capsular polysaccharide itself, or the
      aldobionic acid derived from it, was present in the culture medium.

PMID- 19869998
TI  - THE ACTION OF A SPECIFIC ENZYME UPON THE DERMAL INFECTION OF RABBITS WITH TYPE
      III PNEUMOCOCCUS.
AB  - The action of the enzyme which specifically decomposes the capsular
      polysaccharide of Type III Pneumococcus has been tested in Type III pneumococcus
      dermal infections in rabbits. When injected in sufficient amounts, this enzyme is
      capable of bringing about a favorable and early termination of the experimental
      disease which ordinarily is fatal in nearly all instances. The results of the
      present study yield further evidence that the capsular substance is of great
      importance in pneumococcus infection, since, in so far as known, the only action
      of which the specific enzyme is capable is that of decomposing the capsular
      polysaccharide.

PMID- 19869999
TI  - BRAIN TO BRAIN TRANSMISSION OF THE SUBMAXILLARY GLAND VIRUS IN YOUNG GUINEA PIGS.
AB  - The submaxillary gland virus of guinea pigs was serially transmitted from brain
      to brain in young guinea pigs. The source of virus was the submaxillary glands of
      six groups of stock animals. Brain to brain transfer was effected in two series,
      in one to the second generation and in the other to the third. The transmission
      was evidenced by the presence of nervous symptoms and death and by a typical
      microscopic pathology of the brain. Only certain attempts were successful, ten of
      twenty-three brain to brain injections being fatal with the specific
      histopathology present in five. A few observations suggest that the virus may be
      present spontaneously in the gland and experimentally in the brain without
      cellular changes being demonstrable, or before they are evident. While we were
      able to transmit the virus from brain to brain with fatal results by single
      injections of small doses, this was not readily accomplished and the transmission
      failed after two or three passages. We were unable to show any perceptible
      increase in virulence or adaptation of the virus to the brain tissue of the
      natural host. The histopathology was that of a meningoencephalitis. The
      inflammatory reaction irregularly involved the meninges, the underlying brain
      substance, and the perivascular tissue of the meninges and upper cortical layer.
      These structures were infiltrated with mononuclear cells, many of which contained
      a typical acidophilic inclusion. Congestion of cerebral capillaries uniformly
      occurred and various degrees of recent hemorrhage were frequently found. Necrosis
      was noted only when associated with an occasional area of extensive hemorrhage.
      Similar changes were observed in sections of the spinal cord. When sufficient
      time (15 days or more) elapsed between cerebral inoculation and death, typical
      cellular inclusions were seen in the salivary glands, whereas none was found in
      animals that died earlier (7 to 9 days). Under the first mentioned conditions,
      inclusions were demonstrated in the parotid and mucous portion of the
      submaxillary glands, although in spontaneously infected animals, we failed to
      find the mucous portion involved and other workers report that the parotid is
      spared. About one-third of the stock guinea pigs examined showed cellular
      inclusions in both the nucleus and cytoplasm of epithelial duct cells of the
      serous part of the submaxillary gland. From an analysis of the results of brain
      to brain inoculations, it was evident that spontaneous infection and resistance
      to cerebral inoculation increased with age. The 3rd week of life is the period of
      choice for such experimentation.

PMID- 19870000
TI  - THE VESSELS INVOLVED IN HYDROSTATIC TRANSUDATION.
AB  - The gradient of permeability which exists along the cutaneous capillaries and
      venules is accentuated and broadened in scope by increasing the venous pressure
      moderately. Under such circumstances transudation leading to edema takes place
      most abundantly from the venules. The permeability of the portion of the
      capillary web that is near the arterioles increases only when the venous pressure
      rises so high as to approximate that in the arteries. Under such circumstances
      the gradient of permeability along the small vessels disappears, the capillaries
      and venules everywhere leaking fluid. The character of the vital staining
      developing under such circumstances indicates, like the evidence of previous
      work, that the cause for the gradient is to be sought in a structural
      differentiation.

PMID- 19870001
TI  - THE GRADIENT OF PERMEABILITY OF THE SKIN VESSELS AS INFLUENCED BY HEAT, COLD, AND
      LIGHT.
AB  - The mounting gradient of permeability along the small vessels of the corium is
      essentially unaltered by active hyperemia produced by heat, cold, or light. Only
      when the vascular walls are so damaged that rapid leakage ensues, as shown by the
      development of edema, does the permeability of the capillary web as a whole
      approximate that of the venules. It is plain that the normal gradient of vascular
      permeability depends upon the integrity of the vessel wall. The method of
      experiment described can be utilized for a study of the functional changes which
      result in the lesions due to burning and freezing.

PMID- 19870002
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : II. THE INACTIVATION OF
      THE TUMOR-PRODUCING AGENT BY MONOCHROMATIC ULTRA-VIOLET LIGHT.
AB  - Even though part of the energy of the incident light is probably absorbed by
      chemical entities which play no part in the specific reaction of inactivation,
      nevertheless the wave lengths most active in destroying biological cells or
      agents will presumably be found to be among those absorbed in the highest
      proportion. This would indicate that the curves here presented are approximately
      reciprocal to the coefficients of absorption of particular substances, the
      destruction of which caused the inactivation of the agents or the death of the
      cells. The similarity between the curves for bacteria, virus, and phage, both in
      shape and in total involved energies, suggests the presence of a common factor,
      or of closely related chemical entities, sensitive to ultra-violet light, whereas
      the data for the tumor agent suggest that its inactivation is due to the
      destruction of a substance having an essentially different spectral absorption,
      and therefore of a different chemical character. While the amount of ultra-violet
      energy required to affect the tumor agent is great, it is still less than that
      involved in the inactivation of some of the enzymes (7). A study is under way to
      compare the deduced spectral analysis with the actual coefficients of absorption
      of the highly purified tumor agent.

PMID- 19870003
TI  - THE ASSOCIATION OF PNEUMOCOCCI, HEMOPHILUS INFLUENZAE, AND STREPTOCOCCUS
      HEMOLYTICUS WITH CORYZA, PHARYNGITIS, AND SINUSITIS IN MAN.
AB  - Pneumococci, H. influenzae, and S. hemolyticus are known to be frequent
      inhabitants of the upper respiratory tract, but most workers have not recognized
      any definite relationships between their presence and coryza, sore throat,
      influenzal, and sinusitis attacks (2-5). Dochez, Shibley, and Mills, however, in
      their experimental studies of common cold, state that in both the spontaneous and
      experimentally induced "colds" in anthropoid apes, the "most significant change
      observed has been the increase of activity on the part of the potential pathogens
      habitually present in the throat flora. Coincident with the appearance of
      symptoms, pneumococci, S. hemolyticus, and B. pfeifferi have developed in greatly
      increased numbers and have spread over a wide area of the nasopharyngeal mucous
      membranes. These organisms became at this time conspicuous even in the nose,
      where they are seldom or never present under normal conditions. The same
      phenomena have not been observed in human beings" (6, 7). The essential facts of
      the present observations are that persons free of pneumococci, H. influenzae, and
      S. hemolyticus are in general free of coryza, sore throat, influenzal and sinus
      attacks; that persons who are occasional or periodic carriers of these organisms
      may be negative on tests over long healthy periods, but generally become positive
      during or following attacks and subsequently become negative again; finally, that
      persons who are chronic carriers show during these illnesses increasing numbers
      of organisms in the throat and extension of the organisms to the nose. That these
      organisms may be the actual incitants has been claimed by Park (8); that they are
      secondary invaders is the view of Shibley, Mills, and Dochez who state as a
      result of their experimental work on this subject that "the most important
      significance of viruses of this type [common cold] seems to lie in their capacity
      to incite activity on the part of the more dangerous pathogenic organisms that
      infect the upper respiratory tract" (7). The present observations bring out the
      intimate relationship between these pathogens and upper respiratory tract
      symptoms, but do not disclose the nature of this relationship. Finally, an
      addition has been made to the knowledge of the mode of spread of these organisms.
      A focus of growth and dissemination has been determined in the nasal passages and
      throat of individuals with chronic upper respiratory tract disease and increases
      in numbers of the organisms at the focus and their spread to contacts have been
      related to the winter season and to the occurrence of symptoms in the carrier.
      The observations suggest that the dosage of these organisms in a community is
      controlled by the resistance of the carrier and of the contacts. This view is in
      agreement with the facts derived from studies of native animal infections (9).

PMID- 19870004
TI  - THE EFFECT OF TESTICLE EXTRACT ON THE GROWTH OF TRANSPLANTABLE MOUSE TUMORS.
AB  - Grafts of a transplantable mouse sarcoma designated as No. 180, and those of an
      attenuated strain of a more malignant Sarcoma S/37, treated with testicle
      extract, either fail to grow on inoculation or result in tumors of a lower growth
      rate than the controls. Autografts of spontaneous mouse tumors so treated show
      little if any effect, while the Bashford adenocarcinoma and the unattenuated S/37
      are unaffected. The factor in testicle extract responsible for the retarding
      activity passes readily through a Berkefeld filter and is thermostable.

PMID- 19870005
TI  - STUDIES ON THE NATURE OF THE AGENT TRANSMITTING LEUCOSIS OF FOWLS : I. ITS
      CONCENTRATION IN BLOOD CELLS AND PLASMA AND RELATION TO THE INCUBATION PERIOD.
AB  - The concentration of the transmitting agent of leucosis in fowls, as determined
      by titration, is approximately the same in the suspensions of blood cells and in
      cell-free plasma; the smallest amount of plasma producing leucosis was 0.000001
      cc. and of cell suspension 0.00001 cc. This observation excludes the possibility
      that transmission of leucosis by plasma is due to the presence of a small number
      of leucemic cells in the plasma. The success of inoculations with plasma (20 to
      28 per cent of fowls) is, within wide limits, independent of the amount injected
      (10(-1) to 10(-6) cc.). The percentage of successful inoculations with varying
      quantities of plasma is lower than with corresponding amounts of suspensions of
      cells (33 to 71 per cent). When plasma containing the transmitting agent is
      injected in decreasing amounts the incubation period of the leucosis is
      conspicuously lengthened. With decreasing amounts of a suspension of leucemic
      cells the incubation period is not so frequently nor so greatly prolonged.

PMID- 19870006
TI  - STUDIES ON THE NATURE OF THE AGENT TRANSMITTING LEUCOSIS OF FOWLS : II.
      FILTRATION OF LEUCEMIC PLASMA.
AB  - The agent transmitting leucosis readily passed all types of silicious filters.
      Filtration is particularly successful when the plasma is freed from particles and
      substances that would otherwise obstruct the pores of the filter. Filtration
      through fine filters seems to be facilitated by preceding filtration through
      coarse filters. A comparison of the periods of incubation of leucosis produced by
      unfiltered plasma and plasma passed through silicious filters shows that as a
      result of filtration, the incubation periods are somewhat prolonged. This
      suggests a slight or moderate decrease in the concentration of the transmitting
      agent in the plasma caused by filtration. Filtration tests through collodion
      membranes indicate that the agent transmitting leucosis is much smaller than the
      virus of bovine pleuropneumonia (250 mmicro) and that it approximates the size of
      bacteriophage.

PMID- 19870007
TI  - STUDIES ON THE NATURE OF THE AGENT TRANSMITTING LEUCOSIS OF FOWLS : III.
      RESISTANCE TO DESICCATION, TO GLYCERIN, TO FREEZING AND THAWING; SURVIVAL AT ICE
      BOX AND INCUBATOR TEMPERATURES.
AB  - The filterable agent transmitting leucosis resists drying, retaining its activity
      for at least 54 days. The conditions of successful desiccation have not been
      precisely ascertained. By the addition of glycerin the agent can be preserved for
      at least 104 days. It is not inactivated by freezing in liquid air. At 37.5
      degrees C. it loses its activity within 14 days, but retains some of its activity
      for at least 14 days when kept at 4 degrees C.

PMID- 19870008
TI  - INFLUENCE OF LIGATION OF PANCREATIC DUCTS OF DOGS UPON SERUM AMYLASE
      CONCENTRATION.
AB  - A sharp contrast has been demonstrated in regard to the post-operative amylase
      concentration of the sera of dogs, depending upon whether ligation of the
      pancreatic ducts was or was not a part of an otherwise prescribed operation. The
      characteristic feature is a marked rise of several hundred per cent in serum
      amylase concentration, sustained for several days, which is observed when the
      pancreatic ducts have been ligated.

PMID- 19870009
TI  - AN EXAMINATION OF THE MECHANISM OF PNEUMOCOCCUS IMMUNITY BY MEANS OF BACTERICIDAL
      MEASUREMENTS : I. THE REACTION BETWEEN THE ANTICARBOHYDRATE ANTIBODY AND THE
      PURIFIED SPECIFIC CARBOHYDRATE.
AB  - 1. Type III antipneumococcus serum, after absorption with the specific
      carbohydrate, no longer forms a precipitate with the carbohydrate, but still has
      a definite, though diminished bactericidal action on virulent pneumococci in a
      bactericidal test. 2. Such an absorbed antiserum still retains some of its power
      to neutralize the antibactericidal effect of the specific carbohydrate in a
      bactericidal test, showing that absorption with the carbohydrate does not remove
      all the anticarbohydrate antibody from an antiserum. 3. This carbohydrate
      neutralization test is a very much more delicate method for detecting the
      anticarbohydrate antibody (precipitin) than the precipitin test. 4. There is
      therefore no necessity to predicate another antibody to explain the bactericidal
      action of a carbohydrate-absorbed antiserum, or a similar result in a mouse
      protection test. 5. The specific carbohydrate has a definite antibactericidal
      action, but it is demonstrated that, were it present in this form in the body
      during pneumonia, it could not conceivably be produced in sufficient quantity to
      influence the disease.

PMID- 19870010
TI  - AN EXAMINATION OF THE MECHANISM OF PNEUMOCOCCUS IMMUNITY BY MEANS OF BACTERICIDAL
      MEASUREMENTS : II. THE REACTION BETWEEN THE ANTICARBOHYDRATE ANTIBODY AND TYPE
      SPECIFIC PRODUCTS OF THE ORGANISM.
AB  - 1. There is in the filtrate of a 5 day broth culture of Type III pneumococcus a
      type-specific substance which has a very powerful antibactericidal action. If the
      precipitinogen content of the broth filtrate and the specific carbohydrate is
      taken as the basis of comparison, it requires approximately one thousand times as
      much antiserum to neutralize the broth filtrate as is necessary to neutralize the
      specific carbohydrate. The active substance in the broth filtrate appears to be
      related to the specific carbohydrate. Its possible nature is discussed. 2. A
      similar substance, but in stronger concentration, was found in the filtrate of a
      lung from a Type III pneumonia autopsy. The influence of this substance on the
      disease is discussed. 3. One specimen of Type III convalescent blood, though
      comparatively weak in anticarbohydrate antibody (precipitin) was better able to
      neutralize the broth filtrate and the lung filtrate than a corresponding mixture
      of normal blood and antiserum. Two other specimens of Type II convalescent blood
      neutralized the Type III broth filtrate efficiently.

PMID- 19870011
TI  - THE FURTHER SEPARATION OF TYPES AMONG THE PNEUMOCOCCI HITHERTO INCLUDED IN GROUP
      IV AND THE DEVELOPMENT OF THERAPEUTIC ANTISERA FOR THESE TYPES.
AB  - The unclassified strains known as Group IV have been separated into twenty-nine
      types which are designated by the Roman numerals IV and XXXII. Only a small
      percentage of the pneumococcus strains isolated in New York City for this study
      were left unclassified. The majority of the types gave very slight cross
      reactions, the exceptions being Types II and V, III and VIII, VII and XVIII and
      XV and XXX. In the series of cases studied, Types IV, V, VII and VIII were found
      more prevalent in the lobar pneumonia of adults and Types V, VI a and XIV in
      children. The majority of the types were also found in normal individuals and in
      persons having respiratory infections other than pneumonia. Types VI a and XIX
      were most prevalent in the limited number of strains studied by us. Fourteen of
      the types were found in pneumococcus meningitis; Type XVIII was found most often.
      Antisera suitable for clinical trial have been prepared for fourteen types. From
      the majority of the horses inoculated for more than a year, antisera having 500
      to 1000 units per cc. were obtained. Antisera of lower potency were concentrated
      and preparations obtained equal to or stronger than high grade unconcentrated
      serum. Potent bivalent antisera have been prepared for types which were found to
      give marked cross-agglutination reactions. The results with each type as to
      prevalence, severity of cases, presence in normal individuals, and in spinal
      meningitis, potency of antisera produced for therapeutic trial and virulence of
      strains for mice have been considered under the different type headings.

PMID- 19870012
TI  - QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION : THE DETERMINATION OF SMALL
      AMOUNTS OF A SPECIFIC POLYSACCHARIDE.
AB  - A method, based on the precipitin reaction, is given for the micro determination
      of the specific polysaccharide of Type III pneumococcus. As little as 0.01 mg. of
      S III can be determined. The method should be applicable to any specific
      polysaccharide upon standardization of an homologous antibody solution or
      antiserum in the region of excess antibody.

PMID- 19870013
TI  - STUDIES ON THE CULTIVATION OF THE TYPHUS FEVER RICKETTSIA IN THE PRESENCE OF LIVE
      TISSUE.
AB  - 1. Rickettsia prowazeki can be cultivated for many generations in vitro, without
      diminution in numbers or virulence, in media similar to those described by
      Maitland, Rivers, and others for the cultivation of certain viruses. In all
      probability, such cultures can be maintained indefinitely. 2. It has been
      impossible, thus far, to cultivate the typhus rickettsia without employing living
      tissue.

PMID- 19870014
TI  - THE AGE FACTOR IN THE VELOCITY OF THE GROWTH OF FIBROBLASTS IN THE HEALING WOUND.
AB  - The velocity curve of fibroplasia in the healing of wounds in young rats reached
      its end-point 3 days ahead of a similar curve for adults. Strength and
      fibroplasia were manifest 1 day sooner than in the adults. A study of the
      increments of the curve showed that the rate of fibroplasia during the
      accelerated phase was less in the young and that it lasted longer.
      Correspondingly, retardation appeared later and was less in amount than in the
      curve for the adult rats. The amount of retardation was even less than in the
      curve obtained for adults on a high protein diet, in spite of the fact that in
      this latter curve there was a definite increase in the rate of fibroplasia.
      Healing in the young, therefore, is more rapid than in adults because fibroplasia
      begins earlier and is less retarded, not because the rate of fibroplasia is
      greater. Growth of the young is not hindered by the process of wound healing.

PMID- 19870015
TI  - REACTION OF RABBITS TO STREPTOCOCCI: COMPARATIVE SENSITIZING EFFECT OF
      INTRACUTANEOUS AND INTRAVENOUS INOCULA IN MINUTE DOSES.
AB  - 1. Rabbits were rendered very hypersensitive by relatively small doses of green
      streptococci given intracutaneously, and somewhat less hypersensitive by similar
      doses of heat-killed vaccine prepared from hemolytic streptococci. 2. Animals
      receiving the same doses intravenously gave, upon subsequent testing, lesions
      slightly more marked than normal controls; but these lesions were qualitatively
      hard and nodular compared with the large edematous lesions in the cutaneously
      sensitized group. 3. There was no parallelism between the degree of cutaneous or
      ophthalmic hypersensitivity and agglutinin titer in the blood serum. 4. Bacterial
      hypersensitivity to whole streptococci appears to depend more upon previously
      induced focal infection than upon circulating antibodies.

PMID- 19870016
TI  - I. RENAL THRESHOLDS FOR HEMOGLOBIN IN DOGS : DEPRESSION OF THRESHOLD DUE TO
      FREQUENT HEMOGLOBIN INJECTIONS AND RECOVERY DURING REST PERIODS.
AB  - We use the term "renal threshold for hemoglobin" to indicate the smallest amount
      of hemoglobin which given intravenously will effect the appearance of
      recognizable hemoglobin in the urine. The initial renal threshold level for dog
      hemoglobin is established by the methods employed at an average value of 155 mg.
      hemoglobin per kilo body weight with maximal values of 210 and minimal of 124.
      Repeated daily injections of hemoglobin will depress this initial renal threshold
      level on the average 46 per cent with maximal values of 110 and minimal values of
      60 mg. hemoglobin per kilo body weight. This minimal or depression threshold is
      relatively constant if the injections are continued. Rest periods without
      injections cause a return of the renal threshold for hemoglobin toward the
      initial threshold levels-recovery threshold level. Injections of hemoglobin below
      the initial threshold level but above the minimal or depression threshold will
      eventually reduce the renal threshold for hemoglobin to its depression threshold
      level. We believe the depression threshold or minimal renal threshold level due
      to repeated hemoglobin injections is a little above the glomerular threshold
      which we assume is the base line threshold for hemoglobin. Our reasons for this
      belief in the glomerular threshold are given above and in the other papers of
      this series.

PMID- 19870017
TI  - II. RENAL THRESHOLD FOR HEMOGLOBIN IN DOGS UNINFLUENCED BY MERCURY POISONING.
AB  - The minimal or depression renal threshold for dog hemoglobin is not modified by
      moderate doses of mercuric chloride. This type of renal injury involves the
      epithelium of the convoluted tubules but the glomeruli escape. We are unable to
      explain our findings if we assume that the tubular epithelium takes an active
      part in the passage of dog hemoglobin from the blood into the urine. The evidence
      points toward the glomerular tuft as responsible for the passage of the
      hemoglobin from the blood plasma into the tubules. The glomerular tuft
      establishes the true hemoglobin threshold under these conditions. If the
      convoluted tubules are normal, we note that hemoglobin is taken into the
      epithelium and this explains the high initial renal threshold. With repeated
      hemoglobin injections this tubular epithelium becomes stuffed with hemoglobin
      pigment fractions and can absorb no more, which explains the minimal or
      depression threshold. Further injury of this tubular epithelium with mercury
      causes no change in this minimal renal threshold, unless we produce actual
      tubular obstruction.

PMID- 19870018
TI  - III. TOLERANCE FOR MERCURY POISONING INCREASED BY FREQUENT HEMOGLOBIN INJECTIONS.
AB  - Frequent injections of superthreshold amounts of dog hemoglobin will cause
      deposits of pigment material in the renal tubular epithelium. When this has
      happened this dog will survive minimal lethal doses of mercuric chloride with
      little evidence of renal injury. In fact some dogs will tolerate twice the
      minimal lethal dose without severe reaction. There is no evidence that continued
      injections of dog hemoglobin in these amounts will cause any injury or functional
      disability of the kidney. Rest periods will effect a disappearance of this
      pigment in the renal tubules.

PMID- 19870019
TI  - IV. HEMOGLOBIN INJECTIONS AND CONSERVATION OF PIGMENT BY KIDNEY, LIVER AND SPLEEN
      : THE INFLUENCE OF DIET AND BLEEDING.
AB  - When the minimal renal threshold for blood hemoglobin is exceeded there is
      observed a deposit of iron staining pigment in the epithelium of the renal
      convoluted tubules. At a certain point this epithelium cannot take up more
      hemoglobin and this coincides with the minimal renal threshold level. When the
      injections of blood hemoglobin are kept below the minimal renal threshold level
      we note a complete absence of iron staining pigment in the renal tubular
      epithelium. Given a deposit of iron staining pigment in the tubular epithelium,
      it will slowly disappear during rest periods with no hemoglobin injections.
      Anemia due to bleeding will accelerate this removal of pigment from the renal
      epithelium and this indicates a conservation of material by the kidney for use in
      construction of new hemoglobin. Pigment giving a positive stain for iron will be
      found in the liver and spleen when hemoglobin injections are given, regardless of
      the renal threshold. Removal of this pigment is accelerated by anemia due to
      bleeding and as a rule an anemia period of 2 months at a level of 1/3 normal (40
      to 50 per cent hemoglobin) will render the spleen, liver and kidney free from
      iron staining pigment. Pigment giving a positive iron stain is frequently
      observed in the mesenteric and lower retroperitoneal lymph glands. This is merely
      a drainage of pigment and phagocytes including pigment from some organ in which
      the pigment deposit was primary. In stock dogs in this laboratory the hemoglobin
      level is quite high when the animals are in a perfectly normal state. The blood
      hemoglobin averages 120 to 150 per cent hemoglobin. In such dogs iron staining
      pigment in the spleen is a common finding and on occasion is observed in the
      liver. To establish an accurate base line for the study of iron and iron staining
      pigment storage due to diet intake one must submit these dogs to a preliminary
      anemia period of at least 2 months. Muscle hemoglobin has a very low renal
      threshold and escapes freely into the urine when given intravenously. Contrasting
      with blood hemoglobin this musde hemoglobin under identical conditions does not
      cause the deposit of iron staining pigment within the epithelium of the renal
      tubules. A pigment giving no iron staining reaction may be found in the
      epithelium of the convoluted tubules of the kidney. Whether this is due to
      dietary or other factors is uncertain but this indicates pigment conservation by
      the kidney. Finally we would emphasize again the fact that the kidney is of
      considerable importance in the conservation of hemoglobin and hemoglobin split
      products which presumably are utilized to build up new hemoglobin.

PMID- 19870020
TI  - V. THE IRON CONTENT OF BLOOD FREE TISSUES AND VISCERA : VARIATIONS DUE TO DIET,
      ANEMIA AND HEMOGLOBIN INJECTIONS.
AB  - When hemoglobin is set free in the circulation the kidney plays an important part
      in the conservation of iron. When the renal threshold is not exceeded by the
      hemoglobin in the blood there is little or no excess iron deposited in the kidney
      but when superthreshold doses of blood hemoglobin are given the epithelium of the
      convoluted tubules accumulates much iron and the iron analyses may show 5 times
      normal values. The normal dog (140 to 150 per cent hemoglobin) has a large
      reserve store of iron in the liver, spleen and marrow. Diets may modify this
      storage of iron in these tissues. To bring conclusive proof relating to the
      individual diet factors, the reserve store of iron should be depleted by an
      anemia period of 2 to 3 months. Complete removal of red cells from tissue
      capillaries is essential for accurate iron assays of fresh tissue. The method
      described accomplishes this without causing gross tissue edema. The lowest iron
      content is observed in the pancreas, stomach, jejunum, colon and urinary bladder.
      These figures average from 1 to 2 mg. iron per 100 gm. fresh tissue. This shows
      that smooth muscle and mucous membranes contain little iron. Striated muscle
      (heart, psoas) shows a relatively low iron content but uniform values close to 4
      mg. per 100 gm. tissue. Lungs show a considerable fluctuation with low iron
      values in anemia (3.7 mg.) and higher values in health (6 to 7 mg.). The spleen
      shows maximal fluctuations and the highest reserve storage of iron per 100 gm.
      fresh tissue. The spleen iron analyses show low values in anemia (7 to 15 mg.)
      and wide differences in controls (25 to 50 mg.). With hemoglobin injections the
      iron storage is conspicuous and iron analyses may run as high as l50 to 175 mg.
      iron per 100 gm. fresh tissue. Bone marrow of the rib runs in parallel with the
      spleen as regards iron storage following hemoglobin injections and depletion
      following anemia periods. The liver because of its weight always contains the
      main bulk of the iron stored in the blood free tissues of the body. Its store is
      depleted by anemia even to levels of 4 to 5 mg. iron per 100 gm. fresh tissue. In
      the normal dog the iron store in the liver averages 25 mg. per 100 gm. tissue.
      Frequent hemoglobin injections may increase this level to 31 mg. iron per 100 gm.
      The liver is considered the most active clearing house for iron storage and
      utilization.

PMID- 19870021
TI  - STUDIES IN THE SEROLOGY OF SYPHILIS : VI. THE INDUCTION OF ANTIBODIES TO TISSUE
      LIPOIDS (A POSITIVE WASSERMANN REACTION) IN NORMAL RABBITS.
AB  - More than one-half of normal rabbits contain complement-fixing or precipitating
      antibodies against Wassermann antigens (the alcohol-soluble lipoids of beef,
      rabbit, and human hearts) by a sufficiently sensitive technique. Normal human
      sera tested by the same technique are uniformly negative. The intravenous
      injection of colloidal suspensions of beef and human heart lipoids into rabbits
      occasionally causes a significant increase in this normal Wassermann (antilipoid)
      titre. This may indicate a certain degree of antibody response to the lipoids as
      such; it may be due to the presence in such extracts of traces of foreign
      protein, which would activate the lipoid haptene into a complete antigen; or it
      may be a non-specific increase in a normal antibody, not due to a specific
      antigenic stimulus. Confirming the results of Sachs, Klopstock, and Weil, the
      addition of normal foreign (human) serum to rabbit, beef, and human heart lipoids
      makes them antigenic for rabbits. The intravenous injection of such lipoid-serum
      mixtures usually causes a significant increase in the titre of the complement
      fixing and precipitating antibody against tissue lipoids. The precipitate which
      forms upon the addition of tissue lipoids to human syphilitic serum is by far the
      most efficient antigen for the production, in rabbits, of antibodies to tissue
      lipoids which we have as yet encountered. Rabbits injected intravenously with
      such a precipitate regularly develop a Wassermann titre which is many times
      higher than either the titre observed in human syphilis, or that induced by the
      injection of a normal serum-lipoid mixture. The very marked antigenic property of
      the precipitate as compared with that of a normal serum-lipoid mixture is
      considered to be due to the fact that it contains a foreign protein firmly bound
      to the lipoid particles, namely, the human reagin-globulin with which they have
      combined. This interpretation is supported by the observations (1) that heating
      at 100 degrees C., which does not affect the lipoid constituent of the
      precipitate, destroys its antigenic power for rabbits, and (2) that a similar
      precipitate derived from Wassermann positive rabbit serum instead of syphilitic
      human serum, and therefore containing tissue lipoid in combination with
      homologous (rabbit) protein, is completely non-antigenic for rabbits.

PMID- 19870022
TI  - THE MAINTENANCE OF A NORMAL PLASMA PROTEIN CONCENTRATION IN SPITE OF REPEATED
      PROTEIN LOSS BY BLEEDING.
AB  - 1. Experiments on five dogs are described consisting in the daily removal of
      blood plasma in amount from 25 to 100 cc. the red cells being returned to the
      circulation in Locke's solution. In no case was there a significant drop in
      plasma protein concentration. 2. A gravimetric method for the determination of
      total plasma protein is described. 3. A case is reported of cirrhosis of the
      liver in which over 10 gm. of protein daily was lost in the ascitic fluid during
      a period of 7 months without any lowering of plasma protein concentration. 4. The
      constancy of the plasma protein level and the adequacy of the mechanism of
      regeneration is pointed out.

PMID- 19870023
TI  - THE EFFECTS OF PARATHORMONE AND AMMONIUM CHLORIDE ON THE BONES OF RABBITS.
AB  - 1. A very large single dose of parathormone produced rapid and extensive
      decalcification of the bones of a young rabbit. 2. Gradually increased doses of
      parathormone failed to produce significant changes in the bones of young and
      fully grown adult rabbits. 3. Ammonium chloride, administered by stomach tube was
      without effect on the bones, when given to rabbits treated with parathormone or
      to otherwise untreated rabbits. 4. Calcium lactate did not promote the appearance
      of signs of parathormone overdosage in rabbits during treatment, nor were
      metastatic calcifications observed in the soft tissues after termination of the
      experiment. 5. The rabbit is relatively very resistant to the decalcifying
      effects of gradually increased repeated doses of parathormone, and therefore is
      not satisfactory material for experimental studies of bone changes of chronic
      hyperparathyroidism. 6. The appearance of actively transforming bones of a young
      growing rabbit, particularly at the sites of rapid growth, is not to be confused
      with the more severe fibrous processes produced by parathormone in guinea pigs,
      dogs and rats.

PMID- 19870024
TI  - THE EFFECT OF ANTITESTICULAR SERUM ON THE ENHANCEMENT VALUE OF TESTICLE EXTRACT.
AB  - The experiments reported here show that the infection-enhancing factor of
      testicle extract is neutralized in vitro by an antiserum against homologous
      testicle extract. An antiserum developed against a testicle extract of one
      species does not influence the enhancing and spreading factor of the extract from
      another species. Rabbits immunized against testicle extract do not exhibit any
      alteration in the spreading or enhancing effect of extracts employed later, even
      when the testicle extract used is from the same species as that employed for the
      immunization. Whether the in vitro inactivation of the active factor is a
      specific neutralization, or is the result of adsorption of the factor on the
      flocculate formed, has not been definitely determined. The fact that there is no
      neutralization in vivo, and that the antiserum acts only on extracts from the
      same species, when definite flocculation takes place, tends to emphasize the
      probability that the neutralization is not a direct one, but is incidental to the
      flocculation mentioned.

PMID- 19870025
TI  - THE RACES THAT CONSTITUTE THE GROUP OF COMMON FIBROBLASTS : I. THE EFFECT OF
      BLOOD PLASMA.
AB  - 1. The ability of fibroblasts to mature and to manifest their various potencies
      in any particular medium is inversely proportional to the growth energy which
      they exhibit in that medium. Fibroblasts having access to high concentrations of
      food substances in their environment do not mature, regardless of their origin or
      the age of the animal from which they were derived. They behave as embryonic
      cells. 2. Fibroblasts cultivated in vitro are potentially able to produce cells
      with the structural and functional properties commonly attributed to macrophages.
      This is true regardless of their origin or the length of time which has elapsed
      since their isolation from the origin. 3. The fibroblast and the macrophage are
      considered to represent extreme functional and structural variations of the same
      cell type. 4. The structural and functional characteristics displayed by
      fibroblasts in vitro vary according to their origin and to the changes which take
      place in the composition of the medium in function of time.

PMID- 19870027
TI  - CYTOLOGIC STUDIES ON RHEUMATIC FEVER : I. THE CHARACTERISTIC CELL OF THE
      RHEUMATIC GRANULOMA.
AB  - Scrapings of subcutaneous nodules from ten patients with rheumatic fever were
      examined microscopically after being stained with supravital dyes. From the
      uniform results obtained, the following conclusions have been drawn. 1.
      Supravital staining of cells from these lesions gives information unobtainable
      with ordinary histologic methods. 2. The scrapings show a great predominance of
      certain cells almost entirely devoid of phagocytic power and not characterized by
      the reactions with neutral red which distinguish monocytes, epithelioid cells,
      and clasmatocytes. Hence they differ from the essential cells of the lesions of
      tuberculosis and experimental syphilis. These differences are probably of a
      functional and developmental rather than of a genetic nature. 3. The cells
      probably arise from the undifferentiated mesenchymal elements of loose connective
      tissue, although it is possible that endothelial cells take part in their
      formation in some instances. 4. Since there is little doubt that the subcutaneous
      rheumatic nodules are pathologically identical with rheumatic granulomata else
      where in the body, these conclusions are considered applicable also to the
      Aschoff body cells of the myocardial submiliary nodules.

PMID- 19870026
TI  - STUDIES ON THE COMMON COLD : V. THE RELATIONSHIP OF PATHOGENIC BACTERIA TO UPPER
      RESPIRATORY DISEASE IN INFANTS.
AB  - 1. Bacteriological and clinical observations on respiratory disease in a
      semiisolated infant population over a period of 2 years are recorded. 2. In two
      severe winter outbreaks of respiratory infection a parallel rise in the carrier
      rate of pathogenic organisms was noted. 3. The first autumn outbreak of colds
      seems to favor the dissemination of the pathogenic organisms. 4. The relationship
      of colds to the severer infections is roughly reciprocal. 5. Infants between 8
      and 14 months of age are subject to the most severe infections. 6. The number of
      infants showing positive skin reactions to products of pathogenic organisms
      increases during the winter months. 7. The significance of these findings is
      discussed.

PMID- 19870028
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : VI. THE
      SYNTHESIS OFp-AMINOPHENOLalpha-GLUCOSIDE AND ITS COUPLING WITH PROTEIN.
AB  - 1. The synthesis of p-aminophenol alpha-glucoside has been described. This
      glucoside can be coupled to any protein to yield a synthetic alpha-glucoside
      protein complex. 2. A synthetic beta-glucoside-protein complex has also been
      prepared. 3. These synthetic sugar-protein complexes have been used as immunizing
      antigens in order to ascertain whether alpha- and beta-glucosidic unions
      influence the specificity of the immune response in animals. The results of the
      immunological studies are presented in the following paper.

PMID- 19870029
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : VII.
      IMMUNOLOGICAL SPECIFICITY OF ANTIGENS PREPARED BY COMBININGalpha- AND beta
      GLUCOSIDES OF GLUCOSE WITH PROTEINS.
AB  - The chemical and immunological properties of the p-aminophenol alpha- and beta
      glucosides of glucose are described and correlated. The results are discussed
      with reference to their possible bearing on the chemo-immunological nature of the
      specific polysaccharides of bacterial origin.

PMID- 19870030
TI  - ON THE SEROLOGICAL SPECIFICITY OF PEPTIDES.
AB  - With the idea that studies on the serological properties of peptides may
      ultimately aid in the understanding of the precipitin reactions of proteins,
      antigens have been prepared containing aminobenzoylated dipeptides, namely glycyl
      glycine, glycyl-d, l-leucine, d, l-leucyl-glycine and d, l-leucyl-d, l-leucine.
      These four antigens were found to be different serologically, their specificity
      depending on the structure of the terminal amino acid carrying the free carboxyl
      group, and to a less degree also on the second amino acid. The results were
      obtained by means of precipitin and inhibition tests. Analogies to observations
      on enzyme specificity are discussed.

PMID- 19870031
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : VII. THE RELATION OF HYPERSENSITIVENESS TO LESIONS IN THE LUNGS OF
      RABBITS INFECTED WITH PNEUMOCOCCI.
AB  - 1. The intratracheal injection of egg albumin or pneumococcus protein induces an
      inflammatory reaction in the lungs of rabbits previously inoculated with the
      respective antigen. 2. A similar reaction occurs following intratracheal
      injection of pneumococcus protein into the lungs of rabbits previously inoculated
      with heat-killed suspensions of the bacteria. 3. This reaction appears to be
      related to the presence of circulating antibody and to have the nature of the
      Arthus reaction. 4. A study of the reaction of the lung of rabbits to infection
      caused by intravenous injections of Pneumococcus reveals that (a) reactions occur
      irregularly in the lung; (b) in the lungs in which reactions do occur, the
      histological changes are not different in normal rabbits and in rabbits made
      resistant by previous intravenous or intracutaneous injections of pneumococci. 5.
      Intratracheal injection of pneumococcus protein followed by intravenous injection
      of virulent pneumococci on the next day does not alter the course and character
      of the infection in resistant rabbits. 6. The experiments reported in this paper
      bring no evidences to support the view that the lesions in the lungs of rabbits
      following the intravenous injection of pneumococci are modified by any previous
      state of sensitivity.

PMID- 19870032
TI  - CORNEAL REACTIONS TO BACTERIUM GRANULOSIS AND OTHER MICROORGANISMS.
AB  - THE CONCLUSIONS WHICH MAY BE DRAWN FROM THE RESULTS OF THE EXPERIMENTS HERE
      PRESENTED ARE: 1. The cornea of the rabbit is highly sensitive to the action of
      various injected bacteria. The lesions vary from insignificant, transient changes
      to severe, destructive panophthalmitis, with fine gradations from the mildest to
      the violent form of inflammation. Moreover, animals that receive the same
      organisms show like changes. 2. The varying degree of inflammatory reaction is
      related to the pathogenicity of the special culture employed; as, for example, is
      shown by the reactions to Type I pneumococci and to Bacterium granulosis. It is
      evident that when a microorganism having a certain degree of virulence is used, a
      lesion of localized vasculonebulous keratitis resembling pannus tenuis or
      vasculosus of human trachoma can be induced. Thus Bacterium granulosis, Bacillus
      xerosis, Hemophilus influenzae, Pneumococcus Type II, Streptococcus viridans, and
      gonococcus can cause the pannus-like corneal changes in the rabbit. Of these
      organisms, however, only Bacterium granulosis induces early, uncomplicated and
      enduring keratitic lesions; the others cause first, diffuse keratitis with
      suppurative lesions; then, as a residual effect, transient, localized,
      vasculonebulous changes in the cornea. These changes, in contradistinction to the
      granulosis lesions, are, therefore delayed, complicated, and transient. When, on
      the other hand, the invasiveness and infecting power of the organisms are low, as
      is the case with the filtrable, Gram-negative bacillus and the small, Gram
      negative bacilli ultimately derived from cases of folliculosis, no marked effect
      is produced by their intracorneal inoculation. If the pathogenicity of bacteria
      is high (as shown by Pneumococcus Type I, hemolytic streptococcus, and the
      remaining bacteria), intracorneal inoculation of the microorganisms leads to
      serious suppurative or destructive changes. 3. The results of experiments with
      monkeys indicate that while pannus is not a sequel of experimental trachomatous
      conjunctivitis, a lesion resembling it follows intracorneal inoculation of
      Bacterium granulosis. 4. One can infer from these results, therefore, that the
      stimulus necessary to produce corneal changes in animals, similar to those of
      trachomatous pannus, is an agent having a definite but extremely low power of
      invasiveness and infectivity.

PMID- 19870033
TI  - THE PURIFICATION AND CONCENTRATION OF DIPHTHERIA TOXOID.
AB  - By precipitation with acetone at 4 degrees C. a refined diphtheria toxoid was
      obtained as a dry powder, readily soluble in aqueous solutions. The powder itself
      appears to be stable. When dissolved in half the original volume of physiological
      salt solution, the toxoid remained stable, in the cold room, for a period of 7
      months. Only toxoids should be used which have been completely detoxified by the
      treatment with formalin. The formalin is immediately and completely removed by
      precipitation with acetone. Filtration through a Mandler filter or the addition
      of a preservative did not appear to have any deleterious effect. Incubating at 39
      degrees C. and freezing for 20 hours did not impair its activities. The
      flocculating value of the purified toxoid containing phenol was almost completely
      destroyed by freezing, while when merthiolate was the preservative, it was
      unchanged. Approximately 62 per cent of the nitrogen was eliminated in the
      process with approximately 15 per cent loss in flocculating value. The
      flocculating values were nearly double those of the original material and thus
      corresponded with the concentration, which was onehalf the volume. By this
      method, the antigenic activity of a toxoid below standard may be increased to a
      satisfactory standard. The antigenic activity of the refined product in the
      immunization of guinea pigs may in general parallel its flocculating values but
      the relation between the results of these tests may not be proportional nor
      constant. As an immunizing agent in the guinea pig, the refined toxoid possesses
      an antigenic activity that is equal to, or greater than, that of the
      unconcentrated toxoid.

PMID- 19870034
TI  - COMPARISON OF THE REDUCING POWER OF SOME TYPICAL TRANSPLANTABLE TUMORS AND OF
      TUMORS PRODUCED BY FILTERABLE VIRUSES : WITH AN APPENDIX ON THE METABOLISM OF
      INFECTIOUS MYXOMA OF THE RABBIT.
AB  - 1. The tissues of Rous chicken sarcoma and of the infectious myxoma of the rabbit
      do not possess the oxidation-reduction enzyme succinodehydrogenase, which is
      present in normal tissues and in transplantable tumors. 2. Filterable virus
      diseases (rabbit Virus III, rabbit neurovaccine, rabbit herpes, fowl-pox) produce
      in the tissues affected by them a partial inhibition of succinodehydrogenase.

PMID- 19870035
TI  - ANTIPNEUMOCOCCIC IMMUNITY REACTIONS IN INDIVIDUALS OF DIFFERENT AGES.
AB  - 1. The incidence of pneumococcidal power of the whole defibrinated blood in human
      beings has been shown to vary with age. The age distribution of other type
      specific antibodies varies similarly, insofar as they are frequent enough to be
      compared or technically demonstrable. 2. The incidence of pneumococcidal power of
      the whole defibrinated blood for Type I, Type II, and Type III differs. Type I is
      the rarest, Type II is the most frequent, and Type III is of intermediate
      frequency. The type-specific antibodies responsible for the other tests employed
      show a similar relative frequency in regard to Types I and II, but some variation
      in regard to Type III. 3. The skin reactions to the acetic acid-predpitable
      proteins and autolysates of the pneumococci are negative or rarely positive in
      infants, infrequently positive in childhood, and positive in a high percentage of
      adults.

PMID- 19870036
TI  - SPECIFIC ANTIBODY RESPONSE OF HUMAN SUBJECTS TO INTRACUTANEOUS INJECTION OF
      PNEUMOCOCCUS PRODUCTS.
AB  - The blood of 63 human subjects selected because of the absence of recent
      infections, was studied for its content of specific antibodies against virulent
      strains of Types I, II, and III pneumococci before and after intracutaneous
      injections of minute amounts of pneumococcus products. The simultaneous injection
      of the specific polysaccharides of all three types of pneumococci and of proteins
      and autolysates derived from Types I and II pneumococci was followed by the
      appearance or increase of pneumococcidal power in the whole defibrinated blood
      and, in most instances, by the appearance of mouse-protective antibodies and
      agglutinins for one or more types. A single intracutaneous injection of 0.01 mg.
      of the protein-free type-specific polysaccharide of either Type I, Type II, or
      Type III pneumococci or 4 similar daily injections was followed, in most of 29
      subjects, by the appearance of antibodies against the homologous, but not against
      the heterologous type pneumococci. Some subjects showed a simultaneous lowering
      of a preexisting pneumococcidal power for heterologous or homologous types. A
      single intracutaneous injection of O.1 mg. of pneumococcus protein in 13
      individuals was not followed by the appearance of specific antibodies to any
      appreciable degree. Single intracutaneous injections of small amounts of
      autolysates derived from virulent strains of Type I, II, or III pneumococci were
      followed in 11 subjects by a more or less general rise in the pneumococcidal
      power with the appearance of homologous type agglutinins and protective
      antibodies in about one-third of the subjects.

PMID- 19870037
TI  - REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR
      PRODUCTS : VIII. THE INTERRELATIONSHIPS OF HYPERSENSITIVENESS TO PNEUMOCOCCUS AND
      STREPTOCOCCUS.
AB  - 1. Following repeated intracutaneous injections of heat-killed S or R
      pneumococci, rabbits acquire an increased skin reactivity to the nucleoprotein of
      both Pneumococcus and indifferent Streptococcus. 2. Rabbits acquire a skin
      reactivity to the proteins of both the organisms mentioned after receiving
      intracutaneous injections of heat-killed indifferent streptococci. 3. Injections
      of pneumococci into the skin are followed in some rabbits by an eye sensitivity
      to pneumococcus protein but not to streptococcus protein nor to suspensions of
      either living organism. 4. Injections of indifferent streptococci into the skin
      are followed, in some rabbits, by an eye sensitivity to suspensions of live
      indifferent Streptococcus, but not to R Pneumococcus or to the nucleoprotein of
      either organism. Measured in terms of bacterial specificity therefore, the eye
      sensitivity possesses a specificity which is not shared by the skin sensitivity.
      5. The sera of rabbits injected intracutaneously with pneumococci or indifferent
      streptococci contain agglutinins for both R Pneurnococcus and indifferent
      Streptococcus. 6. Only those animals injected with pneumococci acquire resistance
      to pneumococcal infection.

PMID- 19870038
TI  - THE ANTIPNEUMOCOCCUS PROPERTIES OF NORMAL SWINE SERUM.
AB  - Certain interesting facts have been obtained regarding the action of normal swine
      serum, but in the light of present knowledge it is not easy to interpret them. It
      has been found that the normal serum possesses the property of protecting mice
      from infection with virulent pneumococci, and of agglutinating virulent S
      pneumococi and also avirulent R pneumococci. The protective action of the serum
      is specific, that is, absorption of the serum with pneumococci of one type
      removes or destroys only the property of the serum which is responsible for its
      protective action against pneumococci of that particular type, leaving the serum
      still active against pneumococci of other types. In this particular, therefore,
      the swine serum resembles a polyvalent antipneumococcus serum produced by
      artificial immunization. In other particulars, however, the swine serum differs
      from that produced byartificialimmunization. Inthefirstplace, theprotectiveaction
      exhibited by normal swine serum against type-specific pneumococci is very slight
      compared with that of animals which have been artificially immunized, even though
      the latter have received only a very few injections of the specific antigen.
      Moreover, the protective properties of the swine serum are destroyed by heating
      to 65 degrees C., and they disappear after a few weeks, even if the serum is kept
      in the cold. Also the protective action of the serum is diminished after the
      serum has been mixed with non-type-specific avirulent R pneumococci and the
      latter have been removed by centrifugalization. A further difference between the
      action of swine serum and that of the antipneumococcus serum produced by
      artificial immunization is that although the swine serum is type-specific in its
      action in protecting mice, nevertheless when this serum is mixed with a purified
      type-specific polysaccharide, neither precipitation nor fixation of complement
      results; and, finally, the action of the serum in protecting mice against
      pneumococci of a particular type is not inhibited by the addition of the
      homologous polysaccharide to the serum. These latter facts relating to the
      specific polysaccharide, and especially the fact that the specific protective
      action disappears after applying the so called absorption technique with non-type
      specific organisms, are most difficult to harmonize with the present conceptions
      of the nature of pneumococcus type specificity. It is not proposed at the present
      time to offer any theoretical explanation of these phenomena. The studies have
      also confirmed the observations of Robertson and Sia, that, if a proper technique
      be employed, normal swine serum exhibits the property of agglutinating type
      specific pneumococci, and that the agglutinins for pneumococci of one type may be
      specifically absorbed, leaving those for pneumococci of other types unchanged.
      Finally, it has been shown that swine serum causes the agglutination of avirulent
      R pneumococci. This property of the serum is not destroyed by heating at 65
      degrees C., and therefore probably depends on factors other than those
      responsible for the agglutination of S pneumococci, and for the protective action
      of the serum in mice.

PMID- 19870039
TI  - SPONTANEOUS AND ACQUIRED ACTIVE IMMUNITY TO THE PHENOMENON OF LOCAL SKIN
      REACTIVITY TO BACTERIAL FILTRATES.
AB  - Spontaneous active immunity to the phenomenon of local skin reactivity to
      bacterial filtrates has been demonstrated. In one experiment, the immunity was
      non-specific, while in others it appeared limited to one or two bacterial
      species. Intradermal vaccination of rabbits with bacterial filtrates induced
      active immunity to the phenomenon. The specificity of this immunity was tested
      with graded amounts of toxic factors. The combined intradermal and intravenous
      immunization in these experiments elicited two types of response:- 1. Specific
      immunity, which was obtained in rabbits highly susceptible to the phenomenon
      (i.e., showing reactions with 1 reacting unit). 2. Non-specific immunity which
      was elicited in rabbits with partial spontaneous immunity (i.e. showing no
      reactions with 1 reacting unit, but susceptible to 15 units 1 week later).
      Comparative studies on the reacting potency of "agar washings" and disintegrates
      (Besredka's method, freezing and thawing method) showed that the first washings
      of bacterial cells are considerably stronger than subsequent washings and
      disintegrates. These facts demonstrate once again the extracellular nature of the
      material necessary for the phenomenon. Tentative explanations of the mechanisms
      involved in the specific and non-specific immunity to the phenomenon are
      discussed.

PMID- 19870040
TI  - THE RELATION OF HEART WEIGHT TO THE BASAL METABOLISM AS VARIED BY THYROID
      ADMINISTRATION.
AB  - A linear relationship exists in the albino rat between the heart weight and the
      basal metabolic rate when varied by the administration of active thyroid
      material. It is suggested that this increase in heart weight which follows the
      increase in metabolism after thyroid is in the nature of a simple work
      hypertrophy of the myocardium.

PMID- 19870041
TI  - A VIRUS DISEASE OF PARROTS AND PARRAKEETS DIFFERING FROM PSITTACOSIS.
AB  - The virus of parrots and parrakeets discovered by Pacheco, Bier, and Meyer is
      unrelated to the agent causing psittacosis either in birds or in man. The virus
      is fairly species-specific and manifests itself chiefly by the production of
      areas of focal necrosis in the liver and acidophilic intranuclear inclusions in
      affected cells.

PMID- 19870042
TI  - THE THERAPEUTIC VALUE OF INTRAMUSCULAR DOSAGE OF TYPE I PNEUMOCOCCUS ANTISERA.
AB  - 1. Intramuscular dosage of antipneumococcus sera in a standard dermal
      pneumococcic infection in rabbits is as effective as intravenous dosage provided
      the degree of blood stream invasion be not unusually high. 2. The immediate
      bactericidal effect of doses of serum given intramuscularly is equal to that of
      the same doses given intravenously in the cases of mild and moderately severe
      bacteremias. 3. The intramuscular method of serum administration in human beings
      with lobar pneumonia deserves a carefully controlled clinical trial.

PMID- 19870043
TI  - VIBRIOS FROM THE INTESTINAL TRACT OF THE GRAY RAT.
AB  - Vibrios obtained from the intestinal tracts of wild rats are described. The
      organism is a normal inhabitant of the lower ileum and cecum of the rat and may
      be cultivated from these regions. While these rat organisms are in their growth
      characters and morphology like those found in an intestinal disease of cattle
      they differ serologically from the cow organisms.

PMID- 19870044
TI  - VACCINATION AGAINST YELLOW FEVER WITH IMMUNE SERUM AND VIRUS FIXED FOR MICE.
AB  - 1. After preliminary experiments in monkeys, 15 persons were actively immunized
      by a single injection of a dried mixture of living yellow fever virus, fixed for
      mice, and human immune serum, with separate injections of enough additional serum
      to make up the amount required for protection. 2. One person was similarly
      immunized by injecting immune serum and dried virus separately. 3. By titration
      of the sera of vaccinated persons in mice, it was shown that the immunity rose in
      a few weeks to a height comparable to that reached after an attack of yellow
      fever, and remained there throughout an observation period of 6 months. 4. Yellow
      fever virus could not be recovered from the blood of vaccinated persons or
      monkeys, except when the latter had received less than the minimal effective
      amount of immune serum. 5. Neutralization of yellow fever virus by immune serum
      took place very slowly in vitro at room temperature in our experiments, and could
      not have been an appreciable factor in vaccination with the serum virus mixtures.
      6. A mixture of fixed virus and immune serum retained its immunizing power for 8
      months when dried in the frozen state and sealed in glass. 7. It appears that the
      immunizing reaction after yellow fever vaccination was a part of a true
      infectious process, as was also the observed leucopenia.

PMID- 19870045
TI  - THE ANEMIA OF SCURVY : EFFECT OF VITAMIN C DIET ON BLOOD FORMATION IN
      EXPERIMENTAL SCURVY OF GUINEA PIGS.
AB  - 1. Weight loss, progressive anemia, and a moderate increase in reticulated red
      blood cells occurred in seventeen guinea pigs on a diet deficient in vitamin C.
      2. The histological changes of the bone marrow removed from guinea pigs with
      scurvy showed large numbers of erythrogenic cells, but scant evidence of active
      maturation to the adult erythrocyte. 3. A reticulocyte response was induced in
      guinea pigs with scurvy when fed orange juice daily. 4. The histological changes
      of the bone marrow removed from guinea pigs during the reticulocyte response
      showed large numbers of mitotic figures and relatively more adult red blood cells
      than in the bone marrow from guinea pigs with scurvy that had not been treated
      with orange juice. 5. It is concluded from this study that the anemia of
      experimentally induced scurvy in the guinea pig is largely dependent upon vitamin
      C deficiency resulting in retarded maturation of the red blood cell.

PMID- 19870046
TI  - STUDIES ON GALL BLADDER FUNCTION : VIII. THE FATE OF BILE PIGMENT AND CHOLESTEROL
      IN HEPATIC BILE SUBJECTED TO GALL BLADDER ACTIVITY.
AB  - The data obtained from the experiments on dogs reported in this paper lead us to
      conclude that bile pigment is not absorbed from the gall bladder bile. The mean
      loss of pigment is so small when compared with the amount of water lost that it
      is negligible. Our cholesterol data do not support the concept that this
      substance is secreted into the gall bladder bile of the dog under normal
      conditions. In the majority of experiments there was a loss of cholesterol.
      Indeed we have failed to find any evidence of definite secretion or absorption
      save in the case of the infected gall bladder. We are led to conclude, as did
      Rous and McMaster (15) with regard to bile pigment, that normally there is no
      absorption of cholesterol.

PMID- 19870047
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : IV. ASSOCIATION OF AN
      INHIBITOR WITH THE ACTIVE PRINCIPLE.
AB  - The presence of an inhibiting substance in the chicken tumor is shown by the fact
      that a desiccate of the tumor is more active after it has been washed two or
      three times with water, and that an extract of the tumor is more potent after
      some factor is removed by adsorption on aluminum hydroxide. When the tumor
      producing factor in an extract of a slow-growing tumor has been destroyed by
      heating at 55 degrees C. it is found to have the property of neutralizing a
      highly active tumor extract. This inhibiting property is destroyed by heating
      over 65 degrees C.

PMID- 19870048
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : V. ANTIGENIC PROPERTIES OF
      THE CHICKEN TUMOR I.
AB  - The injection of tumor extracts and their active protein fractions into rabbits
      induced the formation of precipitins and neutralizing antibodies. When the major
      portion of proteins in the tumor extract had been eliminated it induced the
      formation of neutralizing antibodies, but not of precipitins. The tumor agent,
      more highly purified by removal of the viscous fraction, did not induce
      precipitins, and only 2 out of the 15 sera gave any evidence of neutralizing
      bodies. After the removal of the major portion of protein, the extracts showed
      insufficient interaction with the sera to fix complement.

PMID- 19870049
TI  - STUDIES ON VIRULENCE : IV. INFLUENCE ON VIRULENCE OF PNEUMOCOCCI OF GROWTH ON
      VARIOUS MEDIA.
AB  - FROM THE STUDY OF DIFFERENT TISSUE EXTRACTS AS MEDIA FOR THE GROWTH OF
      PNEUMOCOCCI USED IN AN AUTOMATIC TRANSFER DEVICE, CERTAIN INFERENCES ARE
      WARRANTED: 1. Media made from calf lung or heart, or from horse skeletal muscle
      maintain virulence over a long period of time. Conversely, media made from calf
      spleen lead to a decrease in virulence. 2. Lung medium causes an increase in
      virulence of seven strains of pneumococci. 3. Virulence is maintained in normal
      horse serum; but, it rapidly decreases in immune serum, or in pneumococcus
      antibody solution, a finding which confirms the work of Stryker. Immune serum
      freed from protective antibody gives results similar to normal serum. 4. Rabbit
      medium made from the entire animal apparently is less suitable for the
      maintenance of virulence of pneumococci than medium made in the same way from
      guinea pig.

PMID- 19870050
TI  - TYPHUS FEVER : IV. FURTHER OBSERVATIONS ON THE BEHAVIOR OF RICKETTSIA PROWAZEKI
      IN TISSUE CULTURES.
AB  - In tissue cultures grown at 32 degrees C., typhus Rickettsiae increase rapidly
      within the cytoplasm of infected cells up to about the 14th day. At this time
      practically every cell is infected and the majority of cells are distended with
      organisms. This condition remains constant as long as successful cultures of the
      cells can be maintained (up to 52 days). Loss in virulence does not take place
      during this period in vitro. The number of Rickettsia-filled cells found in
      sections and the incubation period of the infection resulting from inoculation of
      cultures from each age group are definitely correlated. The behavior of typhus
      Rickettsiae in dividing cells is described and methods of spread of the infection
      other than by mitosis of cells are discussed. Normal tissues do not become
      infected in vitroto any considerable extent in spite of prolonged proximity to
      heavily infected cultures of scrotal sac exudate. Complete anaerobiosis and
      alterations in pH do not alter the intracellular location of the organism in
      tissue cultures. The organisms are not seen within nuclei of infected cells. They
      remain intact and infective for several weeks in cells which are kept alive but
      not multiplying. They disappear in less than 1 week, however, when the cells
      undergo degeneration.

PMID- 19870051
TI  - TYPHUS FEVER : V. THE EFFECT OF TEMPERATURE ON THE MULTIPLICATION OF RICKETTSIA
      PROWAZEKI IN TISSUE CULTURE.
AB  - The temperature at which tissue cultures infected with typhus Rickettsiae are
      incubated has been shown to exert a marked influence on the intracellular
      multiplication of Rickettsia prowazeki. At 41 degrees C. the organisms were not
      found in the cultures histologically on and after the 2nd day in vitro, and the
      cultures were non-virulent on and after the 3rd day in vitro, in spite of good
      preservation and growth of the cells. At 37.5 degrees C. organisms were absent
      from the cultures histologically and the cultures were non-virulent on and after
      the 11th day in vitro, in spite of good preservation and growth of the cells. At
      32 degrees C. good but slow growth of cells occurred and organisms were found in
      increasing numbers histologically up to about the 21st day in vitro. At this
      time, 50 to 99 per cent (approximately) of the cytoplasmic volume of the cultures
      was occupied by Rickettsiae. From the 21st day to the 51st day (the limit to
      which cultures have been carried successfully) this condition of unrestricted
      multiplication remained practically unchanged. Inoculation of guinea pigs with
      single cultures after varying lengths of time in vitro, (up to the 51st day)
      always resulted in reproduction of typhus in a characteristic manner. At 27
      degrees the cell growth was negligible, but many cells remained alive for 10 days
      or more. Organisms were absent from the cultures histologically and the cultures
      were non-virulent on and after the 18th day in vitro. The only histological
      preparations showing unrestricted multiplication of the organisms (infection of
      the majority of the cells present) were of cultures incubated at 32 degrees C. It
      is believed that the detrimental effect of the higher temperatures (37.5 degrees
      and 41 degrees C.) on the multiplication of the organism is exerted indirectly,
      by stimulation of the defence mechanism of the cells.

PMID- 19870052
TI  - SPOTTED FEVER : I. INTRANUCLEAR RICKETTSIAE IN SPOTTED FEVER STUDIED IN TISSUE
      CULTURE.
AB  - Spotted fever infection has been studied in tissue cultures grown at 32 degrees
      C. The behavior of spotted fever Rickettsiaeis compared and contrasted with that
      of typhus Rickettsiae under similar conditions. The spotted fever organisms
      multiply extensively in the nuclei of cells where they form spherical clusters of
      various sizes. These structures are compared and contrasted with intranuclear
      inclusion bodies.

PMID- 19870053
TI  - STUDIES ON VIRULENCE : V. THE EFFECT OF OXYGEN, NITROGEN, AND CARBON DIOXIDE ON
      THE VIRULENCE OF GROWING PNEUMOCOCCI.
AB  - The growth of a virulent Type I pneumococcus in an automatic transfer device on a
      medium which aerobically maintains virulence results in a decrease in the
      presence of pure oxygen or pure carbon dioxide, but in no change in the presence
      of nitrogen. Whereas partial pressures of oxygen, that is 5 parts with 95 parts
      nitrogen by volume, and 10 parts with 90 parts nitrogen, resulted in a decrease
      in virulence, with 20 parts oxygen and 80 parts nitrogen, the decrease was almost
      negligible. Media which under aerobic conditions failed to furnish suitable
      constituents for maintenance of virulence, that is spleen, aminoid peptone,
      powdered milk, beef infusion, whole rabbit, and rabbit muscle, also failed under
      nitrogen. Media from whole guinea pig kept the organism virulent for 246
      transfers under nitrogen, but with some decrease. Media made from discard mice,
      survivors of pneumococcus infection, furnished conditions under nitrogen, which
      caused first a decrease of virulence, but later after 246 transfers, a
      restoration to a more virulent state. Gradual increase in temperature over a
      period of 10 days from 36.5 degrees C. to 42 degrees C. in a sample of medium,
      which was otherwise suitable for maintenance of virulence under aerobic
      conditions, resulted in a decrease in virulence.

PMID- 19870054
TI  - CELLULAR REACTIONS IN THE MENINGES OF RABBITS TO TUBERCULO-LIPOID, PROTEIN, AND
      POLYSACCHARIDE, COMPARED WITH THE EFFECTS OF TUBERCLE BACILLI.
AB  - 1. Both living and dead tubercle bacilli, as well as tuberculophosphatide, give
      rise to lesions in which the same type of cell is found, a cell which may prove
      characteristic of the meningeal reaction. After the phosphatide this cell is
      produced by the phagocytosis of lipoidal material. The vacuoles of these cells
      are slowly broken into smaller and smaller size until they correspond to the type
      found in the epithelioid cells with coarse vacuoles. This change is much slower
      in the cells of the meninges than in the cells of the omentum and subcutaneous
      tissue. 2. Intrathecal injections of tuberculo-protein produce a characteristic
      rise in temperature in normal and tuberculous rabbits. Both normal and
      tuberculous rabbits, after repeated intrameningeal injections of a given dose of
      tuberculo-protein, may fail to give a rise in temperature and later react to a
      larger dose.

PMID- 19870055
TI  - BODILY CHANGES AND DEVELOPMENT OF PULMONARY RESISTANCE IN RATS LIVING UNDER
      COMPRESSED AIR CONDITIONS.
AB  - 1. 244 albino rats from standard Wistar Institute stock have been kept for
      periods up to 72 days under the following conditions. (a) Barometric pressure:
      3040 mm. Hg. This means a partial pressure of oxygen of 635 mm. Hg and is
      equivalent to an 83.6 per cent oxygen mixture at normal barometric pressure. (b)
      Temperature: 28 degrees C. (c) Humidity: 50 per cent relative. (d) Rate of
      ventilation: 2660 liters per minute for all animals. (e) Food and daily care were
      provided which induced normal growth in rats in the usual laboratory quarters. 2.
      The harmful factor in this environment was the increased oxygen tension. In our
      experiments the acute effects were active hyperemia and edema of the lungs, just
      as have been described by many investigators. 3. Only a small percentage of rats
      die from acute oxygen poisoning at the pressure employed. The majority return to
      good health objectively and survive several months of exposure. 4. Rats under 1
      month of age display no clinical signs of acute oxygen poisoning, while in older
      animals the severity of the reaction and the mortality is directly proportional
      to the advance in age. 5. The symptoms of acute oxygen poisoning appear on the
      3rd day of exposure in adults and reach maximum intensity during the 4th day, all
      deaths occurring at this time. 6. A continued weight loss is found in old rats,
      while the young gain weight, but not with normal vigor. 7. Adaptation to this
      toxic oxygen tension occurs in the albino rat during the first exposure, so that
      on reexposure acute oxygen poisoning does not develop. 8. Respiratory infection
      occurred sporadically in roughly 20 per cent of the normal adult rats in our
      laboratory colony. About the same incidence was found in the experimental rats
      during exposure; in most of these, chronic bronchiectasis and bronchopneumonia
      followed and proved fatal, indicating a lowered resistance in exposed animals. 9.
      Most rats exposed to an 80 per cent oxygen tension late in pregnancy have
      premature litters and die of acute oxygen poisoning, but if exposed early in
      pregnancy the majority survive. 10. Litters born during the first exposure of the
      mother are approximately 50 per cent underweight and die during the first 24
      hours after birth. 11. A female, rendered resistant by a first exposure, produced
      a healthy litter during second exposure. 12. The continuous failure of adults to
      gain in weight and the fact that young animals grow slowly, together with the
      slowly progressing pulmonary pathology (11), indicate that high oxygen tensions
      not only produce acute changes in the lungs but also some alteration in the
      normal physiological processes, which may be termed "chronic oxygen poisoning."

PMID- 19870056
TI  - MORPHOLOGICAL CHANGES IN THE LUNGS OF RATS LIVING UNDER COMPRESSED AIR
      CONDITIONS.
AB  - 1. The alveolar cells in the lungs of young rats are greater in number and size
      than in old rats, a gradual transition to the state in the latter occurring from
      about the 4th to the 6th months of life. 2. On prolonged exposure to an
      environment having an 83.6 per cent oxygen tension, the cellularity of the
      alveoli is increased in both young and old animals, so that after 2 to 3 weeks it
      is impossible to distinguish them by morphological differences. Numerous mitotic
      figures are present in the alveolar cells. This hyperplasia and hypertrophy is a
      change which persists for months after the rats return to normal air. 3. Young
      rats do not develop the symptoms of acute oxygen poisoning, although some
      perivascular edema and dilatation of the lymphatics results on the 4th day of
      exposure, when intense acute pulmonary edema is present in old rats. 4. The
      mortality of acute oxygen poisoning is directly proportional to the age of the
      animals, although the majority of rats under 6 months of age survive this state
      and continue in apparent good health for as long as 72 days. All deaths during
      the acute stage in an 83.6 per cent oxygen tension occur on the 4th day of
      exposure. 5. After 1 month of exposure lesions are to be seen in the small
      arterioles of the lungs, consisting of a thickening and hyalinization of the
      walls with ultimate thrombosis of many. These vascular changes are identical with
      those seen in the arterioles of the kidney in chronic vascular nephritis. 6.
      Around the 45th day of exposure the large pulmonary arteries contain lesions in
      the media. The walls become loose meshed, thickened, and hyalinized, and hyaline
      cartilage formation is associated with these changes. 7. Reexposure of animals
      following an interval of 40 days in normal air subsequent to the first exposure
      of 72 days, does not produce any clinical or pathological changes. An adaptation
      to this toxic oxygen tension is produced during the first exposure, so that
      oxygen poisoning does not occur on second exposure. The increased cellularity of
      the alveolar walls persists. 8. The similarity in the morphological structure of
      the alveoli in young rats and in previously exposed old rats has a definite
      relationship to the adaptation that occurs to an oxygen tension of 83.6 per cent,
      preventing the development of acute oxygen poisoning on reexposure.

PMID- 19870057
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : III. ATTEMPTS AT ISOLATION
      OF THE ACTIVE PRINCIPLE.
AB  - By two methods a protein fraction can be separated out from a Chicken Tumor I
      extract, which carries all the tumor-producing agent. The precipitate can be
      dissolved and reprecipitated a number of times without loss of activity. The
      agent can be largely dissociated from the protein as shown by the fact that
      aluminum hydroxide will adsorb the protein from an extract and leave the agent
      behind. This purified material has a very low protein content, if any, as shown
      by both chemical and biological tests.

PMID- 19870058
TI  - STUDIES ON INFLAMMATION : VIII. INHIBITION OF FIXATION BY UREA. A FURTHER STUDY
      ON THE MECHANISM OF FIXATION BY THE INFLAMMATORY REACTION.
AB  - A concentrated urea solution effectively dissolves fibrin. The injection into the
      peritoneal cavity of a urea solution (30 or 50 per cent) together with or after
      an inflammatory irritant (aleuronat) prevents wholly or in part the local
      fixation of graphite particles or ferric chloride introduced subsequently. The
      histologic picture in the retrosternal lymphatics explains how this comes about.
      When free dissemination of graphite to the retrosternal nodes occurs, the lumen
      of the lymphatic vessel is unobstructed, whereas partial dissemination is
      accompanied by small fibrinous thrombi occluding the lumen in part only. Trypan
      blue injected at the periphery of an inflamed skin area treated with a
      concentrated urea solution and bacteria (Staph. aureus) penetrates readily into
      the area, whereas it fails to do so when introduced around an inflamed area
      consequent on the injection of distilled water and bacteria (Staph. aureus).
      Concentrated urea per se is an inflammatory irritant. Graphite particles injected
      into a peritoneal cavity previously treated with concentrated urea penetrate
      freely to the retrostemal lymphatic nodes; the lymphatic vessel is relatively
      unobstructed. Trypan blue injected into the circulating blood accumulates rapidly
      in cutaneous areas almost immediately after the latter have been treated with
      concentrations of urea ranging from 50 per cent down to 20 per cent. The results
      of this study furnish evidence, in addition to that already provided, that
      fixation of foreign substances is primarily due to mechanical obstruction caused
      by a fibrin network and by thrombosed lymphatics at the site of inflammation. The
      significance of fixation in relation to immunity and its bearing upon some of the
      other processes involved in the inflammatory reaction have been stressed.

PMID- 19870059
TI  - THE EFFECT OF LYMPHOCYTOSIS INDUCED WITH EMBRYONIC EXTRACT ON THE COURSE OF
      EXPERIMENTAL TUBERCULOSIS IN RABBITS.
AB  - 1. Chick embryo extract given intravenously did not favorably influence the
      course of experimental tuberculosis in rabbits, although it did cause
      lymphocytosis and lymphoid hyperplasia. 2. The tuberculous animals treated with
      chick embryo extract showed lower values for hemoglobin and red blood cells than
      tuberculous controls inoculated from the same suspension. 3. Under the conditions
      of these experiments an increase in the number of young, immature cells in the
      lymph nodes was accompanied by more extensive tuberculous lesions in the lymph
      nodes and especially in the germinal centers of the nodes. A possible analogy to
      lymphatic tuberculosis in children is suggested. 4. The observations of previous
      investigators on the progression and later regression of lesions in experimental
      tuberculosis have been confirmed. The distribution, character, and extent of
      lesions have been studied and are presented in tabular form. 5. The presence and
      significance of tuberculous thrombi in the lungs are discussed.

PMID- 19870060
TI  - THE DIPHASIC NATURE OF TUBERCULOSIS IN RABBITS AFTER INTRAVENOUS INOCULATION WITH
      BOVINE TUBERCLE BACILLI.
AB  - It has been shown that in a large group of rabbits inoculated intravenously with
      bovine tubercle bacilli the disease which follows resolves itself into two
      distinct phases. The first phase manifests itself in widespread diffuse lesions
      which subsequently regress. The mortality rate shows a rise and fall during this
      period, which have been correlated with the extent of lesions and with the
      changes in the blood cells. The duration of this phase is approximately 80 to 90
      days. Following this period the mortality rate again rises and falls, during a
      period when all animals show lesions of a chronic nature. In an infected group
      the number of fatalities in the first phase is a function of the size of the
      dose. When the size of the dose and other conditions are held constant, a
      definite basis upon which to compare the reactions of treated animals is
      established. Studies of the blood cells during the course of the disease show
      that the changes in these cells reflect the course of the lesions in the first
      phase when other signs are lacking and offer a valuable means of making an
      estimate of the state of resistance of the animal from time to time. Studies of
      blood counts made on rabbits before their inoculation with tuberculosis were
      analyzed with regard to the relative longevity of the animals. It was found that
      those animals whose blood cells of various sorts deviated least from the modal
      value for the entire group survived longer than those animals whose counts were
      significantly high or low.

PMID- 19870061
TI  - THE ROLE OF HYPERSENSITIVITY IN THE PRODUCTION OF EXPERIMENTAL MENINGITIS : I.
      EXPERIMENTAL MENINGITIS IN TUBERCULOUS ANIMALS.
AB  - 1. When living or dead tubercle bacilli and their products are placed in direct
      contact with the leptomeninges of hypersensitive (tuberculous) animals, there is
      a definite clinical and pathological response. 2. The clinical response is
      characterized by an onset of weakness, twitchings, convulsions and death of the
      animal within 6 to 12 hours. 3. Histologically the central nervous system shows
      an extensive polymorphonuclear exudate distributed throughout the subarachnoid
      spaces of the brain and extending into the perivascular spaces. 4. The intensity
      of the response is directly proportional to the quantity of visceral tuberculosis
      or to the dose of tuberculin employed. 5. When small quantities of tuberculin are
      employed so as to permit the animal to survive longer than 24 hours, there is an
      exudate found in the sulci and at the base of the brain which is characterized by
      small lymphocytes. 6. The non-tuberculous animals when inoculated with tuberculin
      or tubercle bacilli revealed no clinical or pathological response. The
      tuberculous animals, on the other hand, when inoculated with glycerine broth
      always responded by a definite but slight polymorphonuclear exudate. 7. The
      possible relationship of the allergic state to postinfectious complications of
      the central nervous system is discussed.

PMID- 19870062
TI  - I. THE PERMEABILITY OF THE WALL OF THE LYMPHATIC CAPILLARY.
AB  - A technique has been developed for the demonstration of lymphatic capillaries in
      the ear of the mouse by means of vital dyes and for tests of their permeability
      under normal and pathological conditions. The lymphatics become visible as closed
      channels from which the dyes escape secondarily into the tissue. Some of them,
      cross-connections, with extremely narrow lumen, would seem ordinarily not to be
      utilized. There is active flow along the lymphatics of the mouse ear under
      ordinary circumstances. The movement of dye was always toward the main collecting
      system. The valves of the lymphatics as well as fluid flow prevented distal
      spread. There was in addition slow migration, apparently interstitial in
      character, but in the same general direction, of dots of color produced by the
      local injection of dye. The normal permeability of the lymphatics was studied
      with dyes of graded diffusibility. Their walls proved readily permeable for those
      highly diffusible pigments that the blood capillaries let through easily, but
      retained those that the latter retained. Finely particulate matter (India ink,
      "Hydrokollag"), they did not let pass. No gradient of permeability was observed
      to exist along them such as exists along the blood capillaries of certain organs.
      The observed phenomena of lymphatic permeability, like those of the permeability
      of the blood capillaries, can be explained on the assumption that the lymphatic
      wall behaves like a semipermeable membrane.

PMID- 19870063
TI  - II. INDUCED ALTERATIONS IN THE PERMEABILITY OF THE LYMPHATIC CAPILLARY.
AB  - A standardized solution of a vital dye which escapes with some difficulty from
      the lymphatics of the ear of the mouse has been utilized in tests of the
      permeability of the lymphatic wall under various conditions. It has been found
      that this permeability is subject to great change. The slight pressure that
      suffices to prevent lymph flow from the ear,-an organ in which such flow goes on
      normally,-soon results in increased permeability of the obstructed lymphatics
      without as yet any perceptible dilatation of these vessels. Mechanical
      stimulation as for example a stroke with a blunt wire, or scratching so light as
      not to break the epidermis, results in a practically immediate, great increase in
      lymphatic permeability, which is sharply localized to the region pressed upon.
      This increase in permeability, though so great that even hemoglobin is let pass
      by the lymphatics, endures but a few hours. Warming the ear to 43 degrees C. or
      exposure to mild sunlight increases permeability considerably. Slight chemical
      irritation increases it greatly, though not so much that particulate matter is
      let pass. The edema developing as result of lymphatic obstruction or mechanical,
      thermal, or chemical stimulation is preceded by and associated with a large
      increase in lymphatic permeability. The facts are discussed in relation to their
      bearing upon fluid accumulation within the tissue. It is plain that influences
      within the realm of the normal suffice to increase lymphatic permeability and
      that those which lead to edema cause a very great increase in it. In proportion
      as this increase occurs the lymphatics cease to be channels demarcated by a
      semipermeable membrane. It seems certain that the changes must be in some part
      responsible for the local accumulation of fluid. There exist possibilities, on
      the other hand, of a correlation between the functionings of the blood and lymph
      vessels under certain pathological conditions, as during the resorption of edema.

PMID- 19870064
TI  - THE DEGREE OF COMPENSATORY RENAL HYPERTROPHY FOLLOWING UNILATERAL NEPHRECTOMY :
      I. THE INFLUENCE OF AGE.
AB  - Compensatory hypertrophy of the kidney in albino rats becomes less as age
      advances. There is a rapid decrease from 5 days to 60 days of age and then a slow
      diminution throughout adult life.

PMID- 19870065
TI  - THE PRODUCTION OF OSTEOGENIC SARCOMATA AND THE EFFECTS ON LYMPH NODES AND BONE
      MARROW OF INTRAVENOUS INJECTIONS OF RADIUM CHLORIDE AND MESOTHORIUM IN RABBITS.
AB  - The observations in this work suggest that with certain doses of radioactive
      material, the fundamental damage in the lymphoid tissues is to the stem cell and
      that the damage is to the chromatin of the nuclei of these cells. The erythroid
      tissues are apparently less susceptible to radioactive material than the lymphoid
      tissues but an original anemia of secondary type from peripheral destruction may
      eventually be changed to one of primary type through decreased maturation of
      primitive cells in the marrow. The damage of lymph nodes and bone marrow leads to
      atrophy of these organs. The cells of the liver and thymus suffer nuclear damage
      of the same general character as is seen in the lymph nodes, and there is an
      atrophy of these organs. The storage of the radioactive material in the bones
      gave rise to osteogenic sarcomata in two out of seven rabbits surviving from 11
      to 19 months. A repetition of the experiment has been undertaken with more
      intensive studies to test the validity of the findings.

PMID- 19870066
TI  - FURTHER STUDIES ON THE NATURE OF THE PHENOMENON OF LOCAL SKIN REACTIVITY TO
      BACTERIAL FILTRATES: TOXIC FACTORS DERIVED FROM THE BLOOD SERUM.
AB  - Observations reported here seem to demonstrate the liberation or formation of a
      toxic principle in blood serum through a colloidal disturbance in the latter. The
      principle is able to elicit severe injury in tissues made vulnerable by a
      bacterial filtrate.

PMID- 19870067
TI  - EXPERIMENTS ON THE PURIFICATION AND CONCENTRATION OF THE VIRUS OF POLIOMYELITIS.
AB  - Methods employed by Willstatter and his coworkers in the isolation and
      purification of enzymes have been applied to the virus of poliomyelitis. Rhoads
      (6) showed that alumina gel C mixed with poliomyelitis virus in certain
      proportions at an acid pH resulted in the adsorption and inactivation of the
      virus. The experiments in this communication confirm Rhoads' observation, and
      show further that the adsorption as well as the inactivation are reversible;
      i.e., by changing the pH to the alkaline side with M/15 Na(2)HPO(4) it is
      possible to free the virus in a state in which it is again capable of producing
      typical poliomyelitis. These experiments show also that by this process the virus
      undergoes considerable purification by diminution in the concentration of non
      virus-containing substances. Washing the alumina gel C-virus complex with M/5
      NaCl-M/15 KH(2)PO(4) apparently dissociates no virus but is capable of freeing a
      certain amount of extractible organic substances. Furthermore, it is possible to
      increase the degree of purity and concentration of the virus by distillation in
      vacuo, and subsequent repeated adsorptions and elutions. By such partial
      purification and concentration, a virus solution with a minimal effective dose
      (as regards the production of typical poliomyelitis) of 0.0003 cc. was obtained.
      This solution had 0.04 mg. N per cc., and gave negative biuret, xanthoproteic,
      and ninhydrin reactions. These methods offer an opportunity for the preparation
      of a quantity of sufficiently purified and concentrated poliomyelitis virus to
      warrant the beginning of a study of its chemical nature; they also offer a means
      of anchoring the virus to an insoluble, and centrifugable substance (alumina gel
      C), which promises to facilitate various immunological studies, that might
      otherwise have been impossible.

PMID- 19870068
TI  - THE DETECTION OF POLIOMYELITIS VIRUS IN SO CALLED ABORTIVE TYPES OF THE DISEASE.
AB  - Experiments are reported which describe the isolation of poliomyelitis virus from
      the throats of two patients during an attack of so called abortive poliomyelitis
      (Wickman type), or what we have termed characteristic minor illnesses in
      association with poliomyelitis. This finding represents added evidence in favor
      of the belief, previously held by many observers, that certain types of minor
      illness, which accompany an epidemic of poliomyelitis, probably represent mild
      cases of the disease.

PMID- 19870069
TI  - HISTOLOGICAL STUDIES ON HOG CHOLERA : II. LESIONS OF THE VASCULAR SYSTEM.
AB  - In cases of acute hog cholera the earliest and most pronounced lesions occur in
      the capillaries and smaller arteries. Larger arteries and veins are less
      frequently involved. The lesions consist of swelling and proliferation of
      endothelial cells together with retrogressive changes in them and in the other
      parts of the blood vessel walls. The character and degree of these lesions seem
      to be dependent upon the virulence of the virus and, to some extent, upon the
      presence of secondarily invading bacteria. We believe that these lesions should
      be considered a principal feature of the histopathology of hog cholera.

PMID- 19870070
TI  - HISTOLOGICAL STUDIES ON HOG CHOLERA : III. LESIONS IN THE VARIOUS ORGANS.
AB  - 1. The hemorrhages, foci of necrosis, and anemic infarcts met with in the various
      organs in virus hog cholera, result primarily from the vascular lesions described
      in a previous paper of this series. Although they are not dependent on the
      presence of secondarily invading bacteria, their severity is influenced by these
      organisms. 2. The lesions in the lymph nodes, spleen, kidneys, and central
      nervous system seem to be of special diagnostic value in questionable cases of
      hog cholera. The presence of an encephalitis alone does not justify the diagnosis
      of hog cholera because in the central nervous system of swine similar
      inflammatory lesions occur in other diseases.

PMID- 19870071
TI  - LYMPH PRESSURES IN STERILE INFLAMMATION.
AB  - 1. The normal lymph pressure in the legs of anesthetized dogs is not measurable.
      2. The maximum pressure of lymph in the quiescent leg under conditions of sterile
      inflammation is around 120 cm. of lymph. 3. Venous pressure rises immediately in
      a region subjected to sterile inflammation and then slowly returns to normal. The
      rise in lymph pressure follows the rise in venous pressure. 4. Changes in lymph
      flow, lymph pressure, and protein concentration of the lymph occur when the part
      producing lymph is subjected to external temperatures between 50 degrees and 60
      degrees C.

PMID- 19870072
TI  - THE INFLUENCE OF THE PLASMA COLLOIDS ON THE GRADIENT OF CAPILLARY PERMEABILITY.
AB  - The influence of osmotic conditions on the gradient of capillary permeability
      disclosed by the distribution into mammalian muscle of vital dyes has been tested
      experimentally. The percentage of circulating blood proteins was increased in
      rabbits by the injection of compatible plasma, or of compatible serum concentrate
      obtained by means of a new method of ultrafiltration which has proved both rapid
      and effective. It was found that when this had been done and the circulatory
      conditions had stabilized themselves, the gradient of capillary permeability
      still existed, though its effective extent was less than under normal
      circumstances. When the percentage of circulating blood proteins was reduced, on
      the other hand, by repeated bleedings with return of the cells, either as such or
      suspended in the protein-free fluid obtained by dialysis of serum, the extent of
      the gradient of capillary permeability was broadened and dye passed out into the
      tissue more readily than usual from the capillary as a whole. In contrast to
      these findings injection of a very hypertonic dextrose solution during the period
      when dye was escaping had no perceptible effect on the gradient of capillary
      permeability. The observed phenomena cannot be explained by a flow of dye-stained
      fluid into or out of the blood vessels. The gradient of capillary permeability
      exists independently of osmotic conditions, though its extent can be markedly
      influenced by altering the amount of circulating blood proteins. A considerable
      proportion of the dye used to study the gradient is adsorbed upon these proteins,
      as subsidiary experiments have shown. This happening provides a sufficient cause
      for the differences observed in the extent of the gradient when the percentage of
      proteins is increased or diminished. The evidence like that of previous papers
      indicates that the cause for the gradient is to be found in a structural
      differentiation along the capillary, such that the barrier offered by its wall
      progressively diminishes on the way to the venule. Most current estimates of the
      effective osmotic pressure of the blood proteins fail to take into account the
      existence of local differences in permeability along the capillary.

PMID- 19870073
TI  - INCIDENCE OF GASTRIC ULCER IN ALBINO RATS FED DIETS DEFICIENT IN VITAMIN B
      (B(1)).
AB  - 73 per cent of a group of albino rats whose diet was deficient in vitamin B have
      been found to have ulcerations of the gastric mucosa. A control group was found
      to be free from gastric lesions. Of 74 observed lesions eight were chronic,
      indurated ulcers resembling chronic peptic ulcer in man. The chronicity of the
      ulcers seems to be related to the duration rather than the degree of the
      deficiency. The lesions were generally located along the lesser curvature of the
      stomach, as is true in man. The size of the lesions in rat and man are comparable
      if adjustment is made for differences in the sizes of the organs.

PMID- 19870074
TI  - SEROLOGICAL REACTIONS WITH SIMPLE CHEMICAL COMPOUNDS (PRECIPITIN REACTIONS).
AB  - Experiments are described demonstrating the precipitation of azodyes by immune
      sera prepared by the injection of azoproteins containing the same azo component.
      These precipitin reactions prove conclusively the view already advanced on the
      basis of inhibition reactions that antibodies combine specifically with
      substances of small molecular weight. Although in this respect both phenomena
      have the same significance, the precipitin reactions with dyes are simpler in
      that the aid of a protein antigen is eliminated. That specific serological
      precipitin reactions can take place with substances other than proteins has been
      amply demonstrated by studies on bacterial antigens (14) (polysaccharides (15)).
      The present findings show that for the precipitation with immune sera not even a
      high molecular weight of the reactive substance is required. Factors determining
      the tendency to separate out from the liquid upon combination with antibody seem
      to be the colloidal state of the solution and the chemical composition of the
      substance. With regard to the influence of chemical composition, a striking
      example is provided by the suberic acid dye which gives particularly strong
      precipitin reactions, most probably on account of its long aliphatic side chains.
      The results reported may be of use for studies on the mechanism of serological
      precipitation.

PMID- 19870075
TI  - THE INDUCED DEVELOPMENT OF NON-ACID-FAST FORMS OF BACILLUS TUBERCULOSIS AND OTHER
      MYCO-BACTERIA.
AB  - Six strains of mycobacteria,-three human strains, Saranac H-37, T. S., and No.
      90, a bovine strain, B-1, a smegma strain, No. 74, and a Saranac strain of B.
      phlei,-have been made to grow as non-acid-fast organisms by the addition to the
      culture media of a filtered extract of the chromogenic H-37 strain of B.
      tuberculosis. The action of the extract produced acceleration of growth of the
      treated culture, followed by macroscopic and microscopic changes, and
      differentiation into non-acid-fast forms. The bacterial forms grown from these
      treated cultures were pleomorphic, usually consisting of cocci and small rods;
      but branching forms and spore-like bodies also developed. The sterility of the
      extract causing the changes was demonstrated by frequent control inoculations on
      various media, including Kendall's K medium; and autoclaved extracts had the same
      effects as non-autoclaved. After transfer to media suitable for acid growths four
      of the strains reverted not only to acid-fastness but to their original cultural
      characteristics, providing evidence that the non-acid-fast forms were specific
      for the strain.

PMID- 19870076
TI  - MARROW HYPERPLASIA AND HEMOGLOBIN RESERVE IN EXPERIMENTAL ANEMIA DUE TO BLEEDING.
AB  - In long continued severe anemia due to bleeding in dogs we may observe all
      degrees of red marrow spread. The maximal red marrow spread takes in the total
      marrow area in ribs, vertebrae and long bones. The minimal red marrow spread may
      involve but 10 to 20 per cent of this maximal area. All gradations between these
      extremes are observed in this series. The extent of the red marrow spread is not
      dependent upon the length of the anemia period nor is it related to the capacity
      of the dog to produce new hemoglobin and red cells on standard diets. Evidence
      points to the liver as concerned with this hemoglobin production and liver
      function may set the limits for hemoglobin production on these standard diets.
      This in turn may determine the needful red marrow spread. During favorable diet
      periods there is a storage of hemoglobin or hemoglobin precursors which come out
      later in the control periods as finished red cells. This reserve of hemoglobin
      producing material is not stored as mature red cells in the marrow or elsewhere
      but as intermediates stored probably in the liver and red marrow but also perhaps
      in the kidney and spleen. Red marrow very rarely gives evidence of exhaustion
      even after many years of continuous severe anemia (Dog 18-114). This would seem
      to consist of a shrinkage of the red marrow area rather than a degenerative
      change of the red marrow cells. The spleen shows some evidence of erythrogenesis
      in these dogs. Megakaryocytes in some instances are conspicuous (Fig. 6) and
      nests of nucleated red cells are found in the spleen pulp but it is unlikely that
      the spleen contributes any large amount of red cells to the anemic circulation in
      these experiments. There is no evidence that erythrogenesis occurs in the liver
      or lymphatic tissue in these dogs.

PMID- 19870077
TI  - THE INFLUENCE OF PLASMA PROTEIN ON THE CHLORIDE CONTENT OF THE CEREBROSPINAL
      FLUID.
AB  - 1. When the plasma protein of dogs is lowered by plasmapheresis, the
      concentration of chloride and sodium in the plasma and the cerebrospinal fluid
      tends to become the same, a diminishing of the usual disparity which exists in
      the presence of a normal plasma protein. 2. This is in accord with the theory
      that the cerebrospinal fluid is a dialysate, with the choroid plexus acting as a
      simple dialyzing membrane.

PMID- 19870078
TI  - STUDIES ON TYPHUS FEVER : IX. ON THE SERUM REACTIONS OF MEXICAN AND EUROPEAN
      TYPHUS RICKETTSIA.
AB  - 1. The blood of guinea pigs convalescent from Old World and New World typhus
      infection develops agglutinating properties for the tunica and rat Rickettsiae of
      the New World diseases and for the louse Rickettsia of the Old World disease. 2.
      The two microorganisms are closely related, though probably not identical. 3.
      Human convalescents of both varieties of typhus develop agglutinins for both
      types of Rickettsiae. Such Rickettsia-agglutinating properties are parallel with
      the Weil-Felix reaction in the human sera. 4. Rabbits immunized with Weigl louse
      vaccines develop agglutinins for our X-ray rat vaccines and vice versa. In both
      cases the rabbit sera develop agglutinins for Proteus X-19. 5. These experiments
      furnish a further and, we believe, conclusive proof of the etiological role, in
      New World typhus fever, of the Rickettsia bodies first seen in the tunica cells
      of inoculated guinea pigs by Mooser, and obtained in massive amounts by
      ourselves. 6. The serum reactions also provide a further logical basis for
      experiments in prophylactic vaccination with these Rickettsiae.

PMID- 19870079
TI  - THE IMMUNOLOGICAL BEHAVIOUR OF THE SECOND PROTEIN (LIVETIN) OF HEN'S EGG YOLK.
AB  - A comparison of the livetin of egg yolk and serum globulin of the common fowl
      using (a) anaphylactic and (b) precipitin reactions, indicates that the two
      proteins are very closely related, if not identical. The complement fixation test
      does not give the same result but indicates a difference between the two
      proteins. The complement fixation test also shows differences between serum
      euglobulin and serum pseudoglobulin when these proteins, prepared with
      considerable care, cannot be distinguished either by anaphylactic or precipitin
      tests.

PMID- 19870080
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : VI. ACTION OF THE
      ASSOCIATED INHIBITOR ON MOUSE TUMORS.
AB  - Water extracts of desiccates of certain relatively slow-growing strains of
      Chicken Tumors I and X, or the exudates from such tumors, definitely inhibited
      the growth of a mouse sarcoma (Crocker 180), and were without effect on a mouse
      carcinoma (Bashford 63) or Mouse Tumor S/37, a rapidly growing sarcoma derived
      from the stroma of a carcinoma. Extensive control tests with extracts from
      rapidly growing chicken tumors, and from tissues of normal and immune chickens
      showed no inhibiting action. There was no demonstrable action on the mouse tumors
      of sera from immunized rabbits, which neutralize the chicken tumor agent, nor of
      the sera from chickens highly immune to the chicken tumors.

PMID- 19870081
TI  - ACTIVE IMMUNIZATION AGAINST POLIOMYELITIS.
AB  - 1. A single intracutaneous inoculation with a subinfective dose of the virus of
      poliomyelitis produces considerable immunity. 2. Virus-serum combinations produce
      an appreciable immunity, providing just sufficient serum is used to protect the
      animal from paralysis. If there is an excess of serum, the degree of immunity is
      considerably reduced.

PMID- 19870082
TI  - A COMPARISON BETWEEN CONVALESCENT SERUM AND NON-CONVALESCENT SERUM IN
      POLIOMYELITIS.
AB  - 1. Of twenty-nine so called normal urban adults tested, seven had less than two
      fifths, three had two-fifths, two had three-fifths, eight had four-fifths and
      nine had a neutralizing power at least equal to the average of five batches of
      pooled convalescent serum. 2. Known contacts and avowed non-contacts were equally
      represented in the serums of low potency, but in the serums of higher potency,
      the known contacts predominated. 3. The pooled serums of known contacts and of
      non-contacts were respectively a little above and a little below half the
      strength of the average obtained for pooled convalescent serum. 4. Two series of
      early cases of poliomyelitis, the one treated with normal serum of proved
      protective power, the other with convalescent serum, showed no advantage of one
      type of serum over the other.

PMID- 19870084
TI  - A STUDY OF THE THERAPEUTIC MECHANISM OF ANTIPNEUMOCOCCIC SERUM ON THE
      EXPERIMENTAL DERMAL PNEUMOCOCCUS INFECTION IN RABBITS : I. THE PRESENCE IN
      ANTIPNEUMOCOCCIC SERUM OF A NON-ANTIBACTERIAL THERAPEUTIC FACTOR.
AB  - 1. Antipneumococcic serum contains in addition to the antibodies against the
      various bacterial constituents, a non-antibacterial therapeutic factor. 2. The
      non-antibacterial factor has been separated from the antibacterial antibodies by
      absorption with homologous, heat-killed, virulent pneumococci. 3. The non
      antibacterial factor is not type-specific; it is probably species-specific; it is
      not neutralized by concentrated pneumococcus broth culture filtrate. 4. The
      therapeutic effect of the non-antibacterial factor was demonstrated on the
      experimental, dermal pneumococcus infection of rabbits; this effect is
      demonstrable when it is administered per seor in conjunction with a certain
      subeffective dose of serum. 5. Evidence is presented for the assumption that the
      ultimate outcome of pneumococcus infection depends to a considerable extent upon
      this non-antibacterial factor.

PMID- 19870083
TI  - STUDIES ON THE QUANTITATIVE ACTION OF A SPECIFIC ENZYME IN TYPE III PNEUMOCOCCUS
      DERMAL INFECTION IN RABBITS.
AB  - The enzyme which specifically decomposes the capsular polysaccharide of Type III
      Pneumococcus must be used in certain definite amounts in order to bring about the
      recovery of rabbits infected intradermally with this organism. The experiments
      reported in this paper indicate that the minimal amounts of enzyme required bear
      a definite relationship to the severity of the infection as gauged by the number
      of pneumococci present in the circulating blood.

PMID- 19870085
TI  - THE FORMATION OF MACROCYTES AND MICROCYTES FROM RED CORPUSCLES IN HANGING DROP
      PREPARATIONS.
AB  - IN HANGING DROP PREPARATIONS OF NORMAL BLOOD FROM VARIOUS SPECIES OF ANIMALS
      INCLUDING MAN, THE FOLLOWING PROCESSES WERE DIRECTLY OBSERVED FOR THE FIRST TIME:
      1. The process of fusion between two red corpuscles so as to form a round or
      slightly oval macrocyte with normal hemoglobin content, a diameter of 10micro+/-
      and no delle. These macrocytes appear to be slightly thicker in the centre than
      at the periphery. No thickness measurements could be made. 2. The process of
      fusion between two microcytes each 5micro+/- in diameter, so as to form a red
      corpuscle of approximately normal size but with dense hemoglobin and no delle. 3.
      The process of fusion between a red corpuscle and a microcyte, forming a
      macrocyte slightly larger than a normal red corpuscle and exhibiting a normal
      hemoglobin tint but no delle. 4. The process of microcyte formation from red
      corpuscles was seen occurring in four different ways: (a) By the intermittent
      compression of a single red corpuscle by the pull of three or more fibrin threads
      attached to the corpuscle. (b) By the steady, continuous compression of a single
      red corpuscle by the pull of two polar fibrin threads, (c) By intermittent rises
      of intracorpuscular pressure in a red corpuscle due to trauma, (d) By avulsion
      and retraction or contraction of the hemoglobin stroma from the intact surface
      layer of a red corpuscle. Thickness measurements in single microcytes were made
      in rabbit blood. 5. The process of a typical microcyte with dense hemoglobin and
      no delle changing back to a fairly large red corpuscle with practically normal
      hemoglobin tint and with a delle. 6. Macrocytes were seen expelling their
      hemoglobin in a fraction of a second and turning into shadows which were often
      paler than the background, but without any decrease in the visible surface area
      or change in the contour. 7. Extensibility and retractibility (or perhaps
      relaxation and contraction) may be exhibited by the corpuscle as a whole, by
      local sections of both surface layer and stroma, or retractility (contractility
      (?)) may be shown by the hemoglobin stroma alone. On the basis of observational
      evidence it is inferred that: 1. The surface layer of a red corpuscle is probably
      a condensed stroma rather than an anatomically defined membrane. 2. A pigment,
      probably hemoglobin, is present in the surface layer. 3. The surface layer of red
      corpuscles becomes rigid before or during spontaneous hemolysis. 4. Hemoglobin
      exists in an undissolved form in the intact red corpuscle. 5. The transverse
      diameter of microcytes (5micro+/-) represents the maximal shortening of which
      this diameter is capable in normal red corpuscles of man, rabbit and guinea pig
      under the conditions studied. 6. Fusing red corpuscle are destroyed by repeated
      washings with Ringer solution. 7. In stagnating blood there is no increase in
      fusion forms, nor in the production of microcytes.

PMID- 19870086
TI  - STUDIES ON IMMUNITY TO SWINE INFLUENZA.
AB  - Of the two etiological components of swine influenza, only the filtrable virus
      possessed immunizing properties. H. influenzae suis, while essential to the
      production of the disease, played only a secondary and contributory role and,
      alone, conferred no immunity. Serum of swine convalescent from the filtrate
      disease neutralized the swine influenza etiological complex of organism and
      virus. Intramuscularly administered swine influenza virus was incapable of
      inducing illness but did render hogs immune to swine influenza. It is suggested
      that a specific relationship, as regards infectivity, exists between the swine
      influenza virus and the tissues of the respiratory tract.

PMID- 19870087
TI  - STUDIES ON THE SHWARTZMAN PHENOMENON : I. DETOXIFICATION OF MENINGOCOCCUS CULTURE
      FILTRATES.
AB  - Formalin induces a considerable change in meningococcus culture filtrates. This
      consists of a marked decrease in toxidty as concerns both the Shwartzman
      phenomenon and the lethal effect, with relative preservation of the antibody
      combining capacity and antigenicity. A similar modification occurs spontaneously
      in meningococcus culture filtrates on standing. Inasmuch as these changes
      parallel those occurring in the conversion of diphtheria toxin into toxoid, it is
      justifiable to consider such altered meningococcus toxin as meningococcus toxoid.

PMID- 19870088
TI  - INFECTIOUS MYXOMATOSIS (SANARELLI) IN PREGNANT RABBITS.
AB  - Pregnancy in rabbits alters the reactivity of the tissues to the virus of
      infectious myxomatosis. The livers of pregnant animals with the myxoma have a
      central acidophilic necrosis. Secondary lesions in the lungs are much more
      numerous and larger in the pregnant than in the non-gravid animals. In like
      manner the lesions in the spleen are more extensive in the pregnant rabbit. On
      the other hand the skin lesions of the pregnant animal are decreased in size.

PMID- 19870089
TI  - STUDIES ON THE RELATIONSHIP OF STREPTOCOCCUS HEMOLYTICUS TO THE RHEUMATIC PROCESS
      : I. OBSERVATIONS ON THE ECOLOGY OF HEMOLYTIC STREPTOCOCCUS IN RELATION TO THE
      EPIDEMIOLOGY OF RHEUMATIC FEVER.
AB  - Certain factors of climate are favorable to streptococcus respiratory diseases.
      In those tropical environments where hemolytic streptococcus is unusual in the
      throat flora, scarlet fever is unknown and rheumatic fever rare. In New York
      City, however, following epidemic waves of pharyngitis with hemolytic
      streptococcus the incidence of rheumatic fever rises precipitously. The
      correlation between the geographical distribution of hemolytic streptococcus and
      rheumatic fever is a definite one. Furthermore, in New York City during the
      seasons of the year in which hemolytic streptococcus is seldom recovered from the
      pharynx, acute attacks of rheumatism are unusual. Corresponding to the seasonal
      rise in hemolytic streptococcus infections, the curve of incidence of acute
      rheumatism shows a similar form. Among the children of wealthy patients, enjoying
      great protection, hemolytic streptococcus has been recovered infrequently from
      the throat, and rheumatism has not been encountered during this study. Among the
      poor under observation in New York City, however, the organism is found
      frequently in the pharyngeal flora, and rheumatic fever is common. The findings
      suggest that poverty and unhygienic living conditions favor both the activity of
      hemolytic streptococcus in the throat and the incidence of rheumatic fever.
      Moreover, localized outbreaks of rheumatism have been observed frequently
      following epidemics of "sore throat". Bacteriological studies of these upper
      respiratory infections demonstrate a close relationship between the advent of
      hemolytic streptococcus in the throat flora and the outbreak of rheumatic fever
      in susceptible individuals. In addition to these studies of streptococcus
      infections and their relationship to the development of rheumatic fever,
      observations of the rheumatic patient add further emphasis to this association.
      First, among a group of rheumatic children in an isolated environment,
      reactivation of the rheumatic process has been recognized only following the
      advent of hemolytic streptococcus in the throat flora. Also, an investigation of
      families in which several members have rheumatic heart disease has led to the
      same conclusion. Recrudescences of the disease have been observed under a variety
      of conditions among these individuals. However, the one constant factor in the
      outbreaks of recrudescences in rheumatic homes is their association with family
      epidemics of hemolytic streptococcus infection. Moreover, by studying rheumatic
      patients before, during and after transplantation to a tropical environment, it
      has been possible to demonstrate a close relationship between activity of the
      disease process and infection with hemolytic streptococcus. While the rheumatic
      patients remained in the tropics this organism was not recovered from the
      pharyngeal flora, and the disease process seemed quiescent. On return to New York
      City, those individuals who have escaped respiratory infection have remained
      symptom-free. However, of those who have contracted hemolytic streptococcus
      pharyngitis, each has developed a rheumatic attack within 3 weeks after
      infection. Finally, extensive bacteriological studies made in ambulatory
      rheumatic subjects over a period of 4 years have demonstrated that the
      individuals who escape respiratory disease remain free of rheumatic
      manifestations. On the other hand, the majority of rheumatic patients who
      contract hemolytic streptococcus pharyngitis experience shortly afterward a
      definite recrudescence of their disease. In conclusion, there is a close
      relationship between respiratory infection with hemolytic streptococcus and
      activity of the rheumatic process in susceptible individuals.

PMID- 19870090
TI  - STUDIES ON THE RELATIONSHIP OF STREPTOCOCCUS HEMOLYTICUS TO THE RHEUMATIC PROCESS
      : II. OBSERVATIONS ON THE BIOLOGICAL CHARACTER OF STREPTOCOCCUS HEMOLYTICUS
      ASSOCIATED WITH RHEUMATIC DISEASE.
AB  - To determine the nature of the organisms associated with outbreaks of rheumatism
      at The Pelham Home, in a large number of individuals at the Presbyterian Hospital
      Nurses' Training School and among rheumatic subjects in New York City under
      continuous clinical observation, studies of the throat flora have been conducted.
      Hemolytic streptococcus in most instances appeared in the pharynx from 1 to 5
      weeks before the onset of the rheumatic attack. These organisms have been
      investigated with the usual types of bacteriological tests and, in addition, have
      been classified serologically according to Lancefield's technique. The results
      have demonstrated that the organisms were not of a single type, but fell into six
      antigenic groups. The majority of the freshly isolated strains tested were strong
      toxin producers. The organisms producing the strongest toxin were cultures from
      the patients who developed extremely intense rheumatism. About 70 per cent of
      these toxins were neutralized by a monovalent streptococcus antiserum.

PMID- 19870091
TI  - STUDIES ON THE RELATIONSHIP OF STREPTOCOCCUS HEMOLYTICUS TO THE RHEUMATIC PROCESS
      : III. OBSERVATIONS ON THE IMMUNOLOGICAL RESPONSES OF RHEUMATIC SUBJECTS TO
      HEMOLYTIC STREPTOCOCCUS.
AB  - In the first two papers findings were presented which point to a close
      relationship between the incidence of rheumatic fever and the distribution of
      Streptococcus hemolyticus. The fact was emphasized that in the rheumatic subject
      a recrudescence of the disease process is usually preceded by pharyngeal
      infection with hemolytic streptococci. These organisms conspicuous in the throat
      flora during the period of infection preliminary to an attack of acute rheumatism
      fell into six antigenic groups and produced toxins which in 70 per cent were
      neutralized by a monovalent streptococcus antiserum. In the present study, four
      series of observations have been presented, demonstrating the development of
      immune bodies to hemolytic streptococcus during the course of rheumatic fever.
      The agglutination and complement fixation reactions of sera from patients with
      acute rheumatism suggest recent infection with streptococcus. Precipitin tests
      indicate that at the time of appearance of the rheumatic attack, individuals
      develop, in their blood, precipitins to the protein fractions of hemolytic
      streptococcus. That these precipitins may not be entirely specific is recognized
      from their cross-reactions with antigens of chemically related organisms. The
      studies made in association with E. W. Todd of England have demonstrated that at
      the onset of an attack of acute rheumatism, there occurs in each instance a rise
      in the antistreptolysin titer of the patient's serum. This titer is much higher
      than that observed in normal subjects or in patients with bacterial infection
      other than hemolytic streptococcus. This presence of antistreptolysin with an
      N.D. of 0.005 cc. is considered strong evidence of recent infection by hemolytic
      streptococcus. In conclusion, the relationship between the incidence of hemolytic
      streptococcus and the geographical distribution of rheumatic fever, the
      relationship between the recrudescence in the rheumatic subject and infection of
      the throat with hemolytic streptococcus, the development of immune bodies for
      hemolytic streptococcus at the onset of the rheumatic attack and the apparently
      specific relationship of antistreptolysin formation to infection with hemolytic
      streptococcus,-together this combined evidence indicates that the infectious
      agent initiating the rheumatic process is Streptococcus hemolyticus.

PMID- 19870092
TI  - PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: REACTIVATING EFFECT
      OF BLOOD SERA UPON COMPLETELY NEUTRALIZED TOXIC FILTRATES.
AB  - In this paper there are reported observations on a certain new reactivating
      property of normal and immune blood sera of various animal species. The effect of
      the reactivating sera consists in restoration of the toxicity in vivo and in
      vitro of completely neutralized meningococcus and B. coli reacting factors. The
      property is apparently non-specific, heat-labile, lessens on storage, and has no
      relationship to complement. Heating of immune sera to a temperature destructive
      for the reactivating property but innocuous to the neutralizing antibodies,
      raises considerably their neutralizing potency. The possible immunological
      significance of the reactivating property is discussed in this paper.

PMID- 19870093
TI  - PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: FORMATION OF REACTING
      FACTORS IN VIVO.
AB  - In this paper there is described a new method for the demonstration of antigen
      antibody combination, as follows: A rabbit sensitized a week previously to some
      animal protein receives a skin-preparatory injection of a potent bacterial
      filtrate. 24 hours after the skin preparation the rabbit is injected
      intravenously with the same animal protein. From 4 to 5 hours later there appears
      severe hemorrhagic necrosis at the prepared skin site. The incidence of positive
      results is high. A single sensitizing injection and 1 week incubation period are
      sufficient. The test is highly specific unless repeated sensitizing injections of
      large doses of antigen are made. The necessary sensitization can be elicited with
      minute quantities of animal proteins. It is also possible to elicit severe
      reactions in the prepared skin sites of non-sensitized rabbits upon separate
      intravenous injections of non-bacterial and bacterial antigens and homologous
      antibodies (i.e., passive transfer). The relation of the phenomenon of local skin
      reactivity to bacterial filtrates to various fields of immunology is discussed in
      the light of the above observations.

PMID- 19870094
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : VII. SEPARATION OF THE
      ASSOCIATED INHIBITOR FROM TUMOR EXTRACTS.
AB  - The inhibiting factor present in certain relatively slow-growing strains of
      Chicken Tumor I and in Chicken Tumor X is adsorbed from extracts of the
      desiccated tumors by aluminum hydroxide (Willstatter Type C) and can be released
      in effective quantities from this combination by treatment with basic sodium
      phosphate.

PMID- 19870095
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : VIII. THE EFFECT OF
      TESTICLE EXTRACT ON THE RATE OF GROWTH OF CHICKEN TUMOR I.
AB  - Extracts prepared from the testicle tissue of the rat, rabbit, fowl or bull,
      injected together with extracts of Chicken Tumor I or with cells of this tumor,
      showed no definite effect of either enhancement or inhibition as concerned the
      resulting tumors.

PMID- 19870096
TI  - STUDIES ON THE PHYSIOLOGICAL EFFECTS OF FEVER TEMPERATURES : I. A DESCRIPTION OF
      A SERIES OF CONSTANT TEMPERATURE WATER BATHS FOR THE DETERMINATION OF THE THERMAL
      DEATH TIME OF BACTERIA.
AB  - A series of six water baths in one unit, set at 37 degrees , 39 degrees , 40
      degrees , 41 degrees , 41.5 degrees , and 42 degrees C., for the purpose of
      studying the thermal death time of bacteria and of body tissues has been
      described.

PMID- 19870097
TI  - STUDIES ON THE PHYSIOLOGICAL EFFECTS OF FEVER TEMPERATURES : II. THE EFFECT OF
      REPEATED SHORT WAVE (30 METER) FEVERS ON GROWTH AND FERTILITY OF RABBITS.
AB  - 1. The repeated elevation of body temperatures of male and female rabbits to 41
      degrees and 42 degrees C. from 2 to 5 times per week by short radio waves (30
      m.), beginning from 29 to 171 days of age and extending through their first
      period of gestation, failed to injure their growth or to interfere with mating,
      fertilization, or the development of young in utero. Litter mates were kept for
      controls. 2. The rabbits exposed to the short wave fevers showed, in the majority
      of cases, a greater percentage gain in weight than did the control litter mates.
      3. The kindling age of the treated group was, on an average, 2 weeks older than
      the non-treated group. 4. The fever-treated females averaged five and one-half
      young per litter with an average weight of 41 gm., while the untreated females
      averaged seven per litter with an average weight of 36.5 gm. 5. The repeated
      elevation of body temperature by short radio waves is a safe procedure when
      temperatures greater than those within physiological limits are not employed.

PMID- 19870098
TI  - STUDIES ON THE PHYSIOLOGICAL EFFECTS OF FEVER TEMPERATURES : III. THE THERMAL
      DEATH TIME OF TREPONEMA PALLIDUM IN VITRO WITH SPECIAL REFERENCE TO FEVER
      TEMPERATURES.
AB  - 1. The thermal death time of Trefonema pallidumin extracts from lesions in
      rabbits' testes was determined in vitro at fever temperatures using the Zinsser
      Hopkins and Nichols strains. 2. The criteria to determine the persistence of
      infectivity of the heated extract were the following: the development of lesions
      on inoculation into rabbits, dark-field examination of tissue from the lesions,
      the outcome of blood Wassermann tests, and of reinoculation tests. 3. The thermal
      death time of the two strains of spirochetes was approximately the same, although
      the Nichols strain was somewhat the more resistant. In the case of the latter 5
      hours at 39 degrees C., 3 hours at 40 degrees C., 2 hours at 41 degrees C., and 1
      hour at 41.5 degrees C., were required to render infective extracts innocuous to
      other rabbits. 4. The thermal death time of T. pallidum in testicular extracts in
      vitro at fever temperatures is so short as to suggest that induced fever may be
      useful therapeutically in human syphilis.

PMID- 19870099
TI  - STUDIES ON THE PHYSIOLOGICAL EFFECTS OF FEVER TEMPERATURES : IV. THE HEALING OF
      EXPERIMENTAL SYPHILIS LESIONS IN RABBITS BY SHORT WAVE FEVERS.
AB  - 1. Multiple, unsustained fevers (41-42 degrees C.) produced by irradiation in a
      high frequency electrostatic field (10,000 kilocycles) destroyed T. pallidum in
      rabbits with active syphilitic lesions as determined by the injection into normal
      rabbits of extracts prepared from their testes and popliteal lymph nodes. 2. One
      febrile period of 6 hours at a temperature of 41.5-42 degrees C. was likewise
      found to be sufficient to destroy T. pallidum. 3. Infection with T. pallidum
      persisted in a control series of untreated rabbits for as long as 395 days after
      inoculation, but clinical healing occurred in from 3 to 4 months after injection.
      4. The time interval between inoculation and fever treatment, or between the end
      of the fever treatment and reinoculation, did not affect the results. 5. The
      fever treatment was effective at any stage of experimental syphilis in rabbits.

PMID- 19870100
TI  - THE ETIOLOGY OF BARTONELLA MURIS ANEMIA OF THE ALBINO RAT : THE ISOLATION OF
      BARTONELLA MURIS.
AB  - 1. Bartonella muris has been isolated in pure culture on Noguchi's leptospira
      medium from the blood of the splenectomized adult rat suffering with Bartonella
      muris anemia. 2. Bartonella muris is a small, actively motile, Gram-negative
      bacillus. It grows best on media containing blood and on Noguchi's leptospira
      medium. The optimal temperature for growth is 20-25 degrees C. It produces
      neither gas nor acid on media containing sugars. It does not hemolyze blood in
      artificial media. Viability of the cultures in leptospira media was maintained
      for 36 days. 3. With this culture a severe anemia was produced in rats weighing
      30 gm., with the occasional appearance of Bartonella muris bodies on the red
      cells. The anemia occurred within 24 hours, and lasted for 3 to 5 days with
      recovery of the rat. Bartonella muris was recovered in pure culture from the
      blood of these animals. The blood of these rats was infectious for other 30 gm.
      rats. 4. 3 week old rabbits were infected with cultures of Bartonella muris, a
      severe anemia resulting after an incubation period of 48 hours. The organism was
      recovered from the blood on the 5th day after injection. Bartonella muris is non
      pathogenic for adult rabbits. 5. A severe anemia was produced in young guinea
      pigs with cultures of Bartonella muris within 48 hours. The organism was
      recovered on the 2nd and 5th days after injection. Postmortem examination
      revealed changes in the organs similar to those found in splenectomized rats
      suffering with spontaneous Bartonella muris anemia. 6. The infection was
      reproduced in white mice. In one instance a severe anemia developed on the 5th
      and 6th days. The organism was recovered on the 6th day. 7. The anemia was
      produced in splenectomized adult rats of non-carrier stock. The organism was
      recovered from the blood stream of these rats. A marked leukocytosis was noted
      (65,000) at the peak of the anemia as is found in the spontaneous disease in
      infected splenectomized adult rats. 8. Serological tests have thus far failed to
      demonstrate the production of agglutinins, though complement-fixing antibodies
      are present in homologous sera in low dilutions.

PMID- 19870101
TI  - STUDIES ON BARTONELLA MURIS ANEMIA : VI. A LIPOID EXTRACT OF THE SPLEEN THAT
      PREVENTS BARTONELLA MURIS ANEMIA IN SPLENECTOMIZED ALBINO RATS.
AB  - An aqueous lipoid extract of ox spleen was prepared which protects adult male
      albino rats of carrier stock in a large percentage of instances against
      Bartonella muris anemia following splenectomy. It is suggested that the extract
      contains a specific hormonal substance.

PMID- 19870102
TI  - STUDIES ON BARTONELLA MURIS ANEMIA : VII. THE PROTECTIVE ACTION OF COPPER AND
      IRON AGAINST BARTONELLA MURIS ANEMIA.
AB  - The effect on Bartonella muris anemia of adding copper or iron or both to an
      adequate diet was studied. The addition to the diet of copper (0.1 mg. per rat
      per day), or iron (1 mg. per day), or both during a period of 2 days prior to
      splenectomy and 1 month subsequent thereto failed to protect adult albino rats
      against Bartonella muris anemia. The addition of copper to an adequate diet for a
      period of 10 days prior to splenectomy and 1 month subsequent thereto protected
      75 per cent of the rats against the anemia. The addition of iron (1 mg. per rat
      per day) for a period of 10 days prior to and 1 month subsequent to splenectomy
      protected 50 per cent of the rats against this anemia. The addition of both
      copper and iron for a period of 10 days prior to and 1 month subsequent to
      splenectomy protected 75 per cent of these rats against Bartonella muris anemia.
      The addition of copper alone for a period of 2 months prior to and 1 month
      subsequent to splenectomy protected 63 per cent of the rats against Bartonella
      muris anemia. The addition of iron, or of both copper and iron during a period of
      2 months prior to splenectomy and 1 month subsequent thereto protected about one
      third of the rats against Bartonella murisanemia.

PMID- 19870103
TI  - A TRANSMISSIBLE TUMOR-LIKE CONDITION IN RABBITS.
AB  - A tumor-like condition has been observed in a wild cottontail rabbit and has been
      found to be transmissible to both wild and domestic rabbits but not to guinea
      pigs, white rats, white mice, or chickens. The clinical picture of the
      experimentally produced condition and the pathological picture of the original
      and experimentally produced tumors have been described. The tumor has the general
      appearance of a fibroma. Methods used in transmitting the condition and
      satisfactory routes of inoculation have been described and discussed.

PMID- 19870104
TI  - A FILTRABLE VIRUS CAUSING A TUMOR-LIKE CONDITION IN RABBITS AND ITS RELATIONSHIP
      TO VIRUS MYXOMATOSUM.
AB  - The properties of the agent causing a tumor-like condition in rabbits have been
      tested experimentally and the conclusion reached that it is a filtrable virus.
      While the tumor-like condition and infectious myxoma differ markedly in their
      clinical and pathological pictures, they have been found to be related
      immunologically. The relationships of the tumor-producing virus to the virus of
      infectious myxoma, and of the tumor-like condition to malignant neoplasms have
      been discussed.

PMID- 19870105
TI  - AMMONIUM CHLORIDE DECALCIFICATION, AS MODIFIED BY CALCIUM INTAKE: THE RELATION
      BETWEEN GENERALIZED OSTEOPOROSIS AND OSTITIS FIBROSA.
AB  - 1. In all age groups the effects of ammonium chloride administration were found
      to be strikingly dependent upon the calcium intake. 2. Dogs receiving an adequate
      calcium diet and ammonium chloride showed less decalcification than those
      receiving a low calcium diet with or without ammonium chloride. 3. In the younger
      groups the added effect of ammonium chloride to calcium-low diet brought out more
      striking changes than a low calcium diet alone. 4. When the decalcification was
      less severe-in the oldest dogs on the low calcium diet with or without ammonium
      chloride, and in the younger dogs on an adequate calcium intake with ammonium
      chloride -generalized thinning of the bones without marrow fibrosis resulted
      (osteoporosis). 5. When the decalcification was rapid and severe-in the youngest
      dogs on low calcium diet, particularly with ammonium chloride- generalized
      decalcification and secondary marrow fibrosis resulted (ostitis fibrosa). 6.
      Generalized ostitis fibrosa is a rather inclusive term and may be applied to the
      histologic picture which results when clinical or experimental decalcification is
      rapid, and therefore leads to extensive marrow fibrosis. 7. The special
      underlying causes of the decalcification may incidentally contribute features to
      modify the generalized osteoporosis or ostitis fibrosa as in rickets and in von
      Recklinghausen's disease.

PMID- 19870106
TI  - THE MATERNAL TRANSMISSION OF VACCINIAL IMMUNITY IN SWINE.
AB  - The introduction of vaccinia virus into the skin of swine calls forth a typical
      vesicular reaction which may be followed by a solid immunity. This acquired state
      of resistance was utilized in determining the route of immunity transmission from
      sow to young. The suckling young of immune sows, vaccinated on the 7th day or
      earlier, showed no reaction to the virus. Their hand-fed litter mates, however,
      were susceptible and reacted with the formation of vesicles. These observations
      indicate that the porcine placenta is largely impermeable to protective
      substances and establish the fact that colostrum functions as the vehicle for
      their transmission as it does for antibodies.

PMID- 19870107
TI  - STUDIES ON THE BLOOD CYTOLOGY OF THE RABBIT : IX. BLOOD PLATELET COUNTS ON
      HEALTHY MALE RABBITS.
AB  - 1. Repeated platelet counts, 991 in number, were made on 148 adult male rabbits
      of various breeds and types which were specifically selected on the basis of
      physical fitness and continued freedom from disease. The observations extended
      over a 2(1/2) year period (1929-32). 2. A unimodal, peaked, moderately
      asymmetrical distribution curve was obtained and an analysis of the results gave
      the following values: the mean, 532,645 platelets per c.mm.; the median, 520,604
      per c.mm.; the mode, 503,962 platelets per c.mm. respectively. 3. The extent of
      the variation among the counts is shown by the standard deviation of 124,960.
      High platelet counts were found to occur more frequently than low counts, a
      result that is reflected in a significant skew to the right in the frequency
      curve. 4. It was calculated that in healthy male rabbits a platelet count of less
      than 220,000 or more than 845,000 per c.mm. should be considered abnormal.

PMID- 19870108
TI  - THE TRANSMISSION OF NEUROTROPIC YELLOW FEVER VIRUS BY STEGOMYIA MOSQUITOES.
AB  - 1. By the bites of stegomyia mosquitoes carrying neurotropic yellow fever virus,
      encephalitis has been produced both in white mice and in rhesus monkeys. 2. The
      fixed neurotropic strain of virus cannot be maintained in the mosquito host as
      well as can the viscerotropic strains. This is doubtless attributable in part to
      a smaller amount of virus ingested, because of paucity in the blood stream of the
      mammalian host. 3. These experiments furnish additional evidence that the long
      established neurotropic yellow fever virus has changed fundamentally from the
      parent French strain.

PMID- 19870109
TI  - THE CELLULAR REACTIONS TO LIPOID FRACTIONS FROM ACID-FAST BACILLI.
AB  - 1. A comparative study has been made of the cellular reactions induced by
      phosphatides from five strains of acid-fast bacilli. Each of these reactions is
      characterized principally by epithelioid cells and giant cells. 2. The
      phosphatides are first phagocytized by young connective tissue cells or
      monocytes. The lipoid is then dispersed into fine particles with the formation of
      classical epithelioid cells. 3. A comparison has been made of the reactions
      induced by heat-killed and defatted tubercle bacilli with those induced by
      tuberculophosphatide. 4. Further studies have been made to determine whether or
      not the phosphatide causes sensitization to tuberculin. It does not do so. 5. The
      life cycle of the epithelioid cell has been observed in all its stages.

PMID- 19870110
TI  - SOME PHYSIOLOGICAL CHARACTERISTICS OF EPITHELIAL TUMORS OF THE MOUSE.
AB  - 1. The histological and physiological characteristics in vitro of mouse tumors
      have been compared. 2. Twenty-eight adenomas, 31 adenocarcinomas, 18 carcinomas,
      and a series of tumors from 2 transplantable carcinomas and from Ehrlich
      carcinoma have been cultivated in vitro. 3. The adenomas were characterized by
      cells of normal appearance, migrating quickly and organizing in thin membranes,
      by few mitoses, a large acid production, and a rapid digestion of fibrin and egg
      albumin. 4. The carcinomas differed from adenomas in a less rapid and extensive
      migration of epithelial cells, a tendency to grow in bud-like formations, the
      presence of many mitoses, and a lesser acid production and fibrin and albumin
      digestion. 5. Ehrlich carcinoma differed from both adenomas and spontaneous
      carcinomas in the unhealthy state of the cells, their irregular growth, and the
      occurrence of a great many mitoses. Acid production was slight, and digestion of
      egg albumin or fibrin less marked, and even entirely lacking. 6. The adenomas and
      spontaneous carcinomas did not invade embryonic tissue. The transplantable
      carcinomas invaded it slightly, while Ehrlich carcinoma actively infiltrated and
      destroyed it.

PMID- 19870111
TI  - A STUDY OF THE DISSOCIATION OF THE RAWLINS STRAIN OF BACTERIUM TYPHOSUM WITH
      SPECIAL REFERENCE TO ITS USE IN THE PRODUCTION OF ANTI-TYPHOID VACCINE.
AB  - A study of the subcultures of the Rawlins strain of Bacterium typhosum used by
      twelve different laboratories for vaccine production showed that they all
      differed from recently isolated smooth strains in cultural characteristics,
      virulence and protective efficiency. Eleven of these Rawlins cultures gave both
      the flagellar and the somatic type of agglutination in anti-smooth rabbit serum,
      and the one culture so tested produced both flagellar and somatic agglutinins
      when injected into rabbits and man. Agglutination of neither the flagellar nor
      the somatic type can, therefore, be used as a test of the smoothness of a culture
      or as an index of immunity. Since the Rawlins strain differs from the smooth
      phase of Bacterium typhosumin cultural characteristics and in virulence, and is
      much less efficient than smooth strains as a protective antigen; and since the
      selection and maintenance of smooth cultures suitable for vaccine production
      present no serious difficulty, it would seem but logical to substitute virulent,
      smooth cultures for the very old Rawlins strain, if we are to expect the maximum
      protection from antityphoid vaccination.

PMID- 19870112
TI  - THE EXTRACARDIAC ANASTOMOSES OF THE CORONARY ARTERIES.
AB  - Widespread anastomoses of the auricular branches and the coronary branches to the
      pericardial fat with the pericardiacophrenic branches of the internal mammary
      arteries and the anterior mediastinal, pericardial, bronchial, superior and
      inferior phrenic, intercostal and esophageal branches of the aorta have been
      described. The most extensive anastomoses between the cardiac and extracardiac
      vessels are around the ostia of the pulmonary veins. It was possible not only to
      demonstrate the passage of injection mass from the coronary arteries into the
      vessels of surrounding structures, but also to show vessels in the heart injected
      through the thoracic branches of the aorta. This rich potential extracardiac
      coronary collateral circulation is probably of significance in compensating for
      sclerosis of the large trunks of the coronary arteries.

PMID- 19870113
TI  - AUGMENTATION OF THE EXTRACARDIAC ANASTOMOSES OF THE CORONARY ARTERIES THROUGH
      PERICARDIAL ADHESIONS.
AB  - The examination of four hearts, with partial or complete obliteration of the
      pericardial sac by fibrous adhesions, after injection of the coronary arteries
      with a colloidal suspension of lamp black showed that the extracardiac
      anastomoses of the coronary arteries were increased owing to the presence of
      adhesions. In all four instances a particularly rich injection of the parietal
      pericardium was obtained and microscopic examination of the adhesions showed them
      to contain injected vessels, extending from epicardium to parietal pericardium. A
      microscopic study of cleared blocks (3 mm. in thickness) of myocardium and
      attached pericardial adhesions, showed the arborization and anastomosis of
      branches of the arteries of the parietal pericardium with those of the heart.
      This vascularization was not limited to the usual areas of subepicardial fat, but
      was seen in regions not ordinarily containing arterial branches. In no one of the
      four cases were the coronary arteries significantly diseased. In one of the four
      cases, the normal sites of anastomoses between the cardiac and extracardiac
      vessels were destroyed by cutting away the great vessels entering and leaving the
      heart, as well as the peri- and intervascular reflections of parietal
      pericardium. Injection mass was found however, in the arteries of the parietal
      pericardium and the diaphragm, showing that it has passed directly through the
      adhesions from coronary to extracardiac vessels. If the extracardiac anastomoses
      of the coronary arteries constitute a significant reserve for cardiac
      circulation, it would appear that this reserve would be augmented by the presence
      of pericardial adhesions. Direct communication between branches of the coronary
      arteries and the pericardial branches of the internal mammary arteries with free
      anastomosis with the anterior branches of the thoracic aorta is established over
      areas corresponding to the extent of the adhesions. Work is now in progress in
      this laboratory to study the functional significance of such an experimentally
      induced collateral circulation in experimental coronary occlusion.

PMID- 19870114
TI  - STUDIES ON MOUSE LEUKEMIA : VII. THE RELATION OF CELL DEATH TO THE POTENCY OF
      INOCULATED CELL SUSPENSIONS.
AB  - The effect of heat, hypo- and hypertonic salt solutions, glycerin, desiccation,
      and mechanical injury was studied on leukemic lymphoid cells of the mouse, and
      the leukemia-transmitting property of cell suspensions (hypothetical transmitting
      agent) in vitro. The results indicate that leukemia has not been transmitted by
      inoculation without the introduction of living cells. The interval between
      inoculation and death bears an inverse relationship to the number of living cells
      inoculated.

PMID- 19870115
TI  - ALLERGIC LOBAR PNEUMONIA : EXPERIMENTAL STUDY.
AB  - The injection of small amounts (1 cc.) of horse serum into the lungs of normal
      rabbits produces a transient pneumonitis confined to the dorsal aspect of both
      lungs. The injection of the same amount of horse serum into the lungs of rabbits
      that have been previously sensitized to the same serum causes in a high
      percentage of cases a lesion which is confined to one lung with the gross and
      microscopic features of lobar (fibrinous) pneumonia as seen in man.

PMID- 19870116
TI  - THE OCCURRENCE OF ANTIGOITROUS SUBSTANCES IN PLANTS.
AB  - The development of simple goiter in rabbits, which results when they are fed on a
      diet consisting chiefly of cabbage (or other Brassica) can be prevented by the
      feeding of certain fresh plants. Lawn grass, fresh alfalfa, skunk cabbage and
      steamed cabbage press juice have been found effective. Washing Brassicae with
      water improves their goiter-producing action, probably by the removal of goiter
      preventing substances. The antigoitrous effect of plant juices was found to vary
      with the amount of reducing substance other than glutathione present. Skunk
      cabbage press juice, obtained from growing plants during the spring months,
      contained a large amount of iodine-absorbing material, and was very effective in
      involuting hyperplastic glands while juice obtained from mature plants in July
      when the iodine-absorbing material had nearly all disappeared, was quite
      ineffective. Certain extracts from cabbage administered parenterally, containing
      the reducing material, also had a marked involuting action on the thyroid. These
      extracts were practically iodine-free. The substance or substances believed to be
      responsible are easily soluble in water, ethyl alcohol, aqueous ethyl alcohol and
      are precipitable by lead acetate at a pH of 0.68-0.70. They are partially
      destroyed by exposure to air and by steam at 100 degrees . Hexuronic acid
      isolated by Szent-Gyorgyi from cabbage, orange juice and suprarenal glands could
      be the antigoitrous agent. It cannot be glutathione.

PMID- 19870117
TI  - A STUDY OF THE THERAPEUTIC MECHANISM OF ANTIPNEUMOCOCCIC SERUM ON THE
      EXPERIMENTAL DERMAL PNEUMOCOCCUS INFECTION IN RABBITS : II. A COMPARISON OF THE
      THERAPEUTIC EFFECT OF UNREFINED, ANTIPNEUMOCOCCIC SERUM WITH THAT OF ITS VARIOUS
      PROTEIN FRACTIONS: THE ROLE OF THE NON-ANTIBACTERIAL FACTOR.
AB  - The experiments of the preceding communication showed that the therapeutic action
      of antipneumococcic serum depends to a considerable extent upon a certain non
      antibacterial factor. The experiments reported in the present communication had
      two main objects; the first was to determine the distribution of the non
      antibacterial factor among the various protein fractions of the serum, and
      incidentally to correlate this property of the factor with that of certain known
      antibodies, as well as to learn whether or not the protein fractions commonly
      excluded from refined preparations of antipneumococcic serum, have any
      therapeutic value; the second was to determine the role of the non-antibacterial
      factor in the therapy of pneumococcus infection, as exemplified by the
      experimental, dermal, pneumococcus infection in rabbits. To determine the
      distribution of the non-antibacterial factor, Type I antipneumococcic serum was
      fractionated with (NH(4))(2)SO(4), and the antibacterial bodies were absorbed by
      concentrated suspensions of heat-killed pneumococci. The activity of the non
      antibacterial factor in the different protein fractions was then tested for by
      adding varying amounts of the absorbed supernatant liquids to a certain constant,
      subeffective dose of serum. Even though the method of titration has certain
      inherent faults it was possible to ascertain that the non-antibacterial factor
      was apparently associated with all the globulin fractions to a similar degree,
      and to a certain extent with the albumen as well. In this respect the non
      antibacterial factor resembles neither the antibacterial bodies of
      antipneumococcic serum, nor, for example, the known diphtheria or tetanus
      antitoxins. The determination of the relative importance of the antibacterial and
      non-antibacterial factors in the therapy of pneumococcus infection in rabbits,
      was rendered possible by the fact that the various globulin fractions differ in
      their relative content of the two factors. Thus whereas the water-insoluble
      fraction of the globulin, precipitated when the saturation of (NH(4))(2)SO(4) is
      raised from 30 per cent to 50 per cent, contains about 90 per cent of the
      antibacterial (mouse protective) bodies, it apparently contains no more of the
      non-antibacterial factor than the water-soluble fraction. The minimal effective
      doses as well as the mouse protective unit content of the different fractions
      were determined. Before the tests were performed, it seemed that if the
      therapeutic effect of a given dose were to depend chiefly upon its content of
      mouse protective antibody, the amounts required for 1 M.E.D. would be determined
      by the number of mouse protective units it contained; on the other hand, if it
      depended primarily on the non-antibacterial factor, one would expect the amounts
      required for 1 M.E.D. to be of approximately the same volume. Actually the
      therapeutic effect was found not to depend entirely upon either factor, alone;
      the M.E.D.'s varied both in volume and m.p.u. content, the absolute concentration
      of either factor being inconstant and almost proportional to the relative
      concentration of the other. Thus a relative abundance of non-antibacterial factor
      made up for a scarcity of mouse protective antibody (as in the water-soluble
      globulin), and vice versa (as in the water-insoluble globulin). It appears,
      therefore, that when a relatively larger amount of antibacterial bodies are
      acting, less of the non-antibacterial factor is necessary; conversely, when more
      of the non-antibacterial factor is available, less of the antibacterial bodies
      are necessary. The last experiment dealt with the practical question as to
      whether any protein fraction or combination of fractions is as good a therapeutic
      agent as the whole, unrefined serum from which it was derived. Two considerations
      were in mind in making the comparison; one had to do with the quantitative
      recovery of potency, the other with the qualitative effect of the various
      fractions as regards the lesion, course, and duration of the experimental
      disease. The results may be summarized as follows: (a) the total globulin was not
      only as good, but in this instance, definitely better than the original serum;
      (b) the total water-insoluble globulin, although almost as potent as the original
      serum, was qualitatively and quantitatively less effective than the total
      globulin; (c) the removal of the 30 per cent (NH(4))(2)SO(4) fraction not only
      diminished the potency of the remaining globulin to a considerable extent (at
      least 25 per cent), but also seems to have disturbed a certain equilibrium, which
      resulted in an undesirable zone phenomenon. As a result of this zone phenomenon,
      which, it is important to note, was not observed in the agglutination or mouse
      protection tests on the same fractions, the range of effective dosage is very
      narrowly limited. Although the results of agglutination tests correlated well
      with those of the mouse protection tests, both of these showed no parallelism
      with the therapeutic effects of the various fractions on the experimental,
      dermal, pneumococcus infection in rabbits.

PMID- 19870118
TI  - THE MORPHOLOGY OF BACTERIUM SHIGAE CULTIVATED ON VARIOUS MEDIA FAVORABLE TO THE
      DEVELOPMENT OF FILTERABILITY AND LIFE CYCLE FORMS.
AB  - A simple micro motion picture apparatus has been developed which is so
      inexpensive to construct and to operate that it can be used regularly for
      bacteriological research. With this equipment about 6000 feet of film
      representing 600 hours of photography have been made of B. shigae growing upon
      various solid media. These pictures illustrate the principal phenomena
      accompanying the development of this organism on ordinary nutrient media, on
      media consisting exclusively of either peptones or proteins, and on media
      containing small amounts of LiCl. Information has thus been gained concerning the
      existence of a life cycle in the Shiga bacillus and concerning its filterability
      through Berkefeld filters. The formation and history of the various "life cycle
      forms" are recorded but the evidence does not point to them as phases of actual
      cycles. In "filterable" B. shigae cultures-such as those grown in the so-called
      "K" broth or in lithium chloride-containing media-many small and short rods are
      present. It has been found that these dwarfed organisms pass through filters
      impervious to the cells of rapidly growing normal cultures. This offers a simple
      explanation of "quick reversions." The present experiments do not provide
      conclusive information concerning the slower reversions which are supposed to
      occur only after many days of treatment and incubation.

PMID- 19870119
TI  - ACTIVE IMMUNIZATION OF MICE WITH THE POLYSACCHARIDES OF PNEUMOCOCCI TYPES I, II
      AND III.
AB  - 1. Pneumococcus polysaccharides Types I, II and III adsorbed on collodion
      particles, and Types I and III adsorbed on carbon (norit) are antigenic in mice.
      2. Unadsorbed pneumococcus polysaccharide of Type I is antigenic in mice in
      proper dilution. One preparation of Type II polysaccharide was not antigenic,
      while another one immunized against Types I and II. Type III polysaccharide was
      only slightly antigenic against Type III but immunized against Type I. 3. The
      antigenicity of pneumococcus polysaccharide in optimal dosage is tentatively
      explained by an adsorption phenomenon taking place in the body in instances in
      which the polysaccharides had not been adsorbed before injection. 4. The
      aggressin-like action of large doses of pneumococcus polysaccharides Types I, II
      and III is further established.

PMID- 19870120
TI  - IMMUNOLOGICAL REACTIONS BETWEEN AGAR-AGAR AND SOME BACTERIAL ANTISERA.
AB  - 1. As found by Sordelli and Mayer, agar adsorbed on bacteria produces agar
      reacting antibodies in animals injected with these organisms. 2. False cross
      agglutination and precipitin reactions can be produced in sera containing agar
      reacting antibodies by organisms grown on agar. Zozaya's publication in this
      field (3) requires partial revision on this account. 3. There is suggestive
      immunological evidence of chemical similarity between the specifically reactive
      groups of agar-agar, and the C substance of the pneumococcus.

PMID- 19870121
TI  - OBSERVATIONS ON THE CULTIVATION OF VACCINE VIRUS IN LIFELESS MEDIA.
AB  - No evidence was obtained to indicate that vaccine virus is capable of
      multiplication in media consisting of serum, Tyrode's solution, and extracts of
      tissues. Kendall's K. medium is not suitable for the cultivation of vaccine
      virus.

PMID- 19870122
TI  - THE ROLE OF THE SPLEEN IN IRON METABOLISM AS ELUCIDATED BY CHANGES IN THE IRON
      BALANCE AFTER SPLENECTOMY.
AB  - We have estimated the iron balance in six dogs before and after splenectomy, in
      two intact dogs, and in five dogs before and after major operations other than
      splenectomy. In all the animals studied, considerable variation in iron balance
      was observed in the periods used (6 to 14 days). The intact controls had positive
      balances, the one followed for a year and a half having over 0.4 mg. per kilo per
      day, except when fasting or on an inadequate intake. The iron of urine, lost
      hair, dandruff, etc., which was not included in the determinations, would be far
      from sufficient to restore equilibrium. Of five animals subjected to major
      operations other than splenectomy, all of which in preoperative periods had
      positive balances varying between 0.423 mg. to 0.075 mg. per kilo per day, three
      showed a positive balance of from 0.989 mg. to 0.057 mg. and two showed negative
      balances of from 0.02 to 0.18 mg., the last two having anemia in the period of
      study while the others had none. Of the six splenectomized dogs, five showed a
      greater tendency to loss of iron after splenectomy (i.e., either a change from a
      positive to a negative balance or to an increasedly negative or lessened positive
      balance). This was not always apparent until some days after splenectomy and
      coincided approximately with the period of developing anemia. The removal of the
      spleen was usually found therefore to be transiently associated with increased
      excretion of iron. It is not possible to demonstrate, however, that the increased
      loss of iron is the cause of the anemia, and the matter awaits further
      investigation before the reason of its occurrence is made clear. An adequate iron
      intake in an intact animal was usually accompanied by a positive balance, though
      in splenectomized animals during the period of anemia it was frequently
      accompanied by a negative balance. Gain in weight in intact animals likewise was
      associated with a positive balance; but in the three instances in which gain of
      weight occurred during periods of anemia, after splenectomy or other operations,
      it was associated with a negative balance. Weight maintenance was also associated
      with a positive balance except in one instance of severe postsplenectomy anemia.
      Loss of weight was not sufficiently associated with a negative balance to make it
      seem a definite factor influencing the balance, per se, although about one-third
      of the periods of loss of weight were associated with negative balances.

PMID- 19870123
TI  - STUDIES ON BARTONELLA MURIS ANEMIA : VIII. CHANGES IN THE CHEMICAL CONSTITUENTS
      OF THE BLOOD DURING THE ANEMIA.
AB  - 1. The blood chemistry of normal adult rats and of splenectomized adult rats
      suffering with Bartonella muris anemia has been studied. 2. Non-protein nitrogen
      rises with the increase in severity of the anemia. Total serum proteins, serum
      albumin and serum globulin decrease slightly. Uric acid remains unchanged. 3.
      Serum chloride concentration remains unchanged, but the concentration of
      chlorides in the blood increases. 4. An acidosis as estimated by the carbon
      dioxide-combining capacity of the blood is observed at the height of the
      infection. 5. The blood sugar decreases and the liver glycogen is depleted in
      rats with a hemoglobin content of the blood of 10 per cent. 6. Total fats and
      fatty acids are increased at the height of the anemia. Total cholesterol, the
      lipoid phosphorus and lecithin are diminished in amount. 7. These changes result
      from the infection or the anemia. Splenectomy itself plays no part in the changes
      observed in the chemical constituents of the blood in Bartonella muris anemia of
      adult albino rats.

PMID- 19870124
TI  - IMMUNITY REACTIONS OF HUMAN SUBJECTS TO STRAINS OF PNEUMOCOCCI OTHER THAN TYPES
      I, II AND III.
AB  - 1. A group of 72 human subjects were studied with respect to the immune reactions
      of their blood and sera to Types I, II and III pneumococci and to 4 other types
      (V, VI, VIII and IX) previously included in Group IV. 2. The same general
      relationships were observed for all of these types as were previously
      demonstrated for Types I, II and III. Each type was specific in relation to the
      bactericidal action of normal human blood and the protective action of normal
      human serum. 3. The frequency with which pneumococcidal action for any pair of
      types was present for both or absent for both in the same blood samples was
      slightly greater than that calculated from the frequencies with which each of the
      types was killed separately. 4. No closer correlation could be demonstrated
      between the reaction of the blood of these subjects to Types II and V or between
      Types III and VIII pneumococci, types related in their reaction with artificially
      prepared immune sera, than was observed between unrelated strains.

PMID- 19870125
TI  - A CORRELATION BETWEEN THE HISTOLOGICAL CHANGES AND THE FATE OF LIVING TUBERCLE
      BACILLI IN THE ORGANS OF REINFECTED RABBITS.
AB  - 1. Immunity to reinfection is a function of the increased capacity of the
      mononuclear phagocytes to destroy tubercle bacilli and varies directly with the
      extent of the primary lesion; however it is rarely sufficient to annihilate
      completely the microorganism. This acquired immunity is superimposed on the
      natural resistance of a given organ. 2. In the presence of sufficient immunity,
      such as occurs with the persistence of an extensive primary lesion, small numbers
      of tubercle bacilli are destroyed by the mononuclear cells in situ without local
      or general infiltration of the tissues by polymorphonuclear or mononuclear
      leucocytes. Larger numbers of bacilli are destroyed within 24 hours by an
      accelerated formation of sharply localized nodules of mononuclear phagocytes.
      These progress no further and are absorbed or result in inconspicuous microscopic
      collections of epithelioid and giant cells. 3. In the presence of less immunity,
      such as occurs when the primary lesion has almost completely healed, the
      immediate inflammatory reaction is more intense and diffuse and persists longer.
      It results in a less rapid disappearance of the bacilli and in a more extensive
      formation of tubercles. These appear much earlier than in the normal animal and
      soon resolve. 4. Tubercle bacilli of reinfection may be destroyed even though the
      primary lesion in the lung and kidney is progressive. This is due to an
      unhindered extracellular multiplication of the bacilli in the caseous foci that
      undergo softening and excavation. Resistance may be overwhelmed by the spread of
      tremendous numbers of living bacilli from these foci through the bronchi or renal
      tubules, while the moderate numbers of reinfecting bacilli reaching the organs by
      way of the blood stream are destroyed.

PMID- 19870126
TI  - THE EFFECT OF ACIDS AND OTHER SUBSTANCES IN THE PRODUCTION OF ACUTE GASTRIC
      ULCERS.
AB  - Although other investigators have attempted to demonstrate that histamine has the
      power of producing acute ulcers when injected locally into the stomach wall, our
      experiments show clearly that this is a very inconstant finding for, of six
      instances, we were only able to obtain a small healed mucosal ulcer in one. Even
      when dilute acid (0.3 per cent hydrochloric acid) was fed to these animals they
      did not develop ulcers or erosions. It has also been stated that histamine, given
      subcutaneously, may produce ulcers secondarily to oversecretion of acid,
      especially when at the same time histamine has been injected into the stomach
      wall. We have been unable to confirm this observation. In our series of
      experiments on dogs which were observed over a varying period of time ranging
      from 4 to 95 days we utilized other substances in addition to histamine. After
      establishing controls, sterile water, normal saline, 50 per cent glucose, skimmed
      milk, whole milk, omnadin, lipiodol, bismuth subcarbonate, pituitrin (S.),
      activin, histamine, adrenalin and insulin were injected into the muscular coat of
      the stomach and it was found that such procedures rarely produced any definite
      changes in the stomach mucosa even when supplemented by the feeding of dilute
      hydrochloric acid (0.3 per cent hydrochloric acid). We were able to demonstrate
      conclusively that the trauma involved in our operative procedure could not in
      itself account for any of the pathological findings. We were also able to show
      that the pressure due to the injected materials did not produce erosions or
      ulcerations. The injections of acids produced varying results. Diluted acid (0.3
      per cent) injected into the stomach wall gave almost uniformly negative results
      but when combined with the feeding of acid of equal strength erosions were
      occasionally produced. Our results with 0.5 per cent hydrochloric add were also
      inconstant. The 1 per cent hydrochloric acid produced, in many instances,
      definite ulcerations even when not accompanied by the feeding of acid.

PMID- 19870127
TI  - LESIONS OF THE NERVOUS SYSTEM IN VITAMIN DEFICIENCY : I. RATS ON A DIET LOW IN
      VITAMIN A.
AB  - Under the conditions of these experiments, which consisted essentially of
      maintaining rats on a ration adequate in all dietary essentials as far as is
      known except vitamin A, the following changes were produced in the nervous
      system. 1. Degeneration of the medullary sheaths of the brachial plexuses and
      sciatic nerves, and less often of the vagus nerves. Such lesions were not found
      in the optic nerves. 2. Degeneration of the medullary sheaths of the sensory
      tracts on the periphery of the spinal cord and in the posterior columns. Much
      less frequently similar lesions were found in both the crossed and uncrossed
      pyramidal tracts. 3. Changes of the same nature in the posterior nerve roots and
      less frequently in the anterior nerve roots of the spinal cord. Evidence was
      adduced to indicate that the changes in the sensory tracts of the spinal cord
      followed those in the posterior nerve roots. With the onset of muscular weakness
      and incoordination in these animals anatomic changes like those just described
      were found at necropsy, but they were not present for any appreciable period
      preceding the onset of these clinical signs. For a short but undetermined period
      following clinical signs of recovery from the nervous disease, marked lesions
      were still present in the nervous system at necropsy. These lesions in the
      nervous system were produced by a ration containing no cereals which might have
      contributed a "toxic" substance to account for the degeneration of the myelin
      sheaths. Neither does a deficiency in unsaturated fatty acids appear to have
      played a role in their development.

PMID- 19870128
TI  - STUDIES ON THE ETIOLOGY OF SPONTANEOUS CONJUNCTIVAL FOLLICULOSIS OF MONKEYS : I.
      TRANSMISSION AND FILTRATION EXPERIMENTS.
AB  - Spontaneous folliculosis of Macacus rhesus monkeys-a type of follicular
      conjunctivitis associated with marked, local, inflammatory reactions-is
      apparently a disease sui generis, due to a specific infectious agent. It can be
      transmitted from monkey to monkey by means of subconjunctival injection of
      suspensions, and by conjunctival swabbing of the secretions, of affected tissues,
      or by contact of normal animals with folliculosis monkeys. The agent causing
      folliculosis has failed in our hands to pass through Berkefeld and Seitz filters,
      even those of an unusual degree of permeability; and the lesions that it causes
      show no cellular inclusions suggestive of the action of a virus. The condition is
      due apparently to an organism of low grade pathogenicity. The essential
      histopathological structure corresponds to that of a folliculoma (16) which,
      while not identical with a granuloma, bears certain resemblances to the latter.
      The studies here reported concern only one species of monkey, Macacus rhesus.
      Further investigations will be carried out on different species of Anthropoidea
      and other animals.

PMID- 19870129
TI  - BIOLOGICAL STUDIES OF THE TUBERCLE BACILLUS : II. A NEW CONCEPTION OF THE
      PATHOLOGY OF EXPERIMENTAL AVIAN TUBERCULOSIS WITH SPECIAL REFERENCE TO THE
      DISEASE PRODUCED BY DISSOCIATED VARIANTS.
AB  - In the preceding pages we have presented evidence which we believe furnishes new
      light on the disease process in avian tuberculosis. From a well known strain of
      avian tubercle bacillus, A(1), four variants have been dissociated, each
      manifesting distinct colony topography and physical and chemical characteristics.
      From these studies we have learned that the variants are sometimes unstable, not
      only in vitro but also in vivo, and that this characteristic is one of the
      prominent factors influencing both the advancement and retrogression of the
      disease. The four variants remain fairly stable in vitro provided they are
      cultivated on proper culture media. About 80 per cent smooth S and flat smooth
      F.S. colonies will develop true to type on egg media; and rough R and the
      chromogenic Ch when cultivated on gycerine agar media, in about the same
      percentage. An early non-specific eosinophilia followed inoculation, no matter
      which variant was used. This usually subsided by the 18th hour. The early stages
      of tubercle formation produced by all the variants appeared similar. First there
      appeared an aggregation of eosinophiles and their ingested bacilli within the
      tissues and then followed replacement by large mononuclear cells which wandered
      in and phagocyted both eosinophiles and bacilli. After the formation of tubercles
      composed only of large mononuclear cells, certain differences between the
      virulent and avirulent variants became apparent. There was also a direct
      relationship between the dosage and the extent of the disease. In our experience
      from 0.16 to 0.25 mg. gave the most uniform results. If S variant was used, the
      early non-specific eosinophilia was followed by a second rise which continued to
      ascend, running parallel with the total leucocyte count. There was a slow
      increase of monocytes and a corresponding decrease of lymphocytes. The
      microscopic lesions, 2 weeks after inoculation, were composed of irregularly
      shaped clumps of necrosing large mononuclear cells. The margins were clear-cut
      and bordered by few or no lymphocytic cells. By the 3rd and 4th weeks
      eosinophiles began to migrate into the centers of the tubercles and abscess
      formation became evident. Death usually occurred after 5 or 6 weeks, although
      this varied with the dosage. The appearance of the lesions suggested an acute
      "toxic" nature, as manifested (1) by marked enlargement of the spleen and liver,
      (2) by the short fatal course of the disease, which never became very extensive,
      (3) by the presence of few organisms within the tubercles, (4) by destruction of
      reticulum and (5) by the marked response of the blood leucocytes. After
      inoculation with F.S. variant the early non-specific eosinophilia disappeared,
      returning again at the terminal stage, 5 to 6 weeks later. The number of
      eosinophiles then ascended sharply, accompanied by a marked leucocytosis which
      continued until death. During this eosinophilia a monocytosis occurred and
      lymphocytes fell away rapidly. During the 2nd week, clumps of closely packed
      large mononuclear cells containing masses of phagocyted bacilli were seen. In the
      3rd and 4th weeks there appeared a prominent peripheral zone of hyalin,
      collagenous-like material associated with an increased reticulum formation which
      apparently walled off the lesion. The bacilli within the tubercle multiplied
      rapidly, it seemed as though they were more resistant to destruction than the S
      organisms, perhaps due to their higher lipin content. As a result of their rapid
      increase, progression of the tubercle continued, with necrosis and abscess
      formation, accompanied by the dissemination of the organisms both locally and
      distantly to new uninvolved tissue. Wide extension of the disease followed due to
      the increase in numbers of bacilli, terminating with death usually during the 5th
      and 6th weeks. The manifestations of "toxin" damage shown in S disease were not
      so marked until the approach of the end-stage. We interpret the type of lesion
      produced by the F.S. variant as a foreign body tubercle to distinguish it from
      the acute "toxic" nature of the S. A quantitative chemical determination showed
      that this organism contained 20.14 per cent lipin whereas in the S variant it was
      only 15.03 per cent. Following inoculation with R variant the initial
      eosinophilia returned to normal within 24 hours. There was then an increase of
      both lymphocytes and monocytes, the latter exceeding the former for a time.
      Later, usually after the 2nd month, the lymphocytes again became predominant over
      the monocytes, approaching the normal base line. Eosinophiles failed to react.
      This blood picture indicated a successful resistance against the infecting
      organisms, and was supported by the pathological findings. None of the chickens
      of this group died during the period of study (79 days) although infecting doses
      of 0.25 mg. were used. Necropsies on four chickens revealed no macroscopic
      evidence of disease approximately 11 weeks after inoculation. Microscopic lesions
      were present in the spleen and liver of some cases. In chickens inoculated 11
      weeks previously these tubercles consisted only of very small, discrete clumps of
      degenerating mononuclear cells often surrounded by a border of lymphocytes.
      Necrosis, abscess formation or caseation was not found. Their small size and
      appearance was evidence of their retrogressive character. Isolated giant cells
      were rarely seen. It was impossible to find bacilli within these tubercles. In
      one instance it was possible to show complete innocuousness of this organism in
      the tissues, as far as producing recognizable tuberculous lesions. Reticulum
      played little part in the development of the lesion and it was neither increased
      or destroyed. Following inoculation with the chromogenic Ch variant the initial
      eosinophilia declined by the 24th or 42nd hour count and from then on remained
      low. The lymphocytes showed little decrease. A prominent monocytosis of prolonged
      character usually occurred during the 3rd to 6th weeks and was then displaced by
      a return of the lymphocytes. By the end of the period of observation the
      differential count had closely approached the normal values. Again the blood
      picture was truly representative of the relatively benign character of the
      lesions. The tubercle formation, even after 93 days' duration of the disease,
      remained limited to small clumps of two or three large mononuclear cells showing
      some degeneration. Lymphocytic cells were usually present within and about the
      lesion. There was never any evidence of abscess formation or actual necrosis.
      Bacilli could not be found within these tubercles. The reticulum in relation to
      the lesion showed neither increase nor destruction. None of the chickens died
      though a dose of 0.5 mg. was used. In three chickens infected with S variant, the
      blood picture did not follow the pattern set by the others similarly inoculated.
      Either a high monocytosis replaced the usual eosinophilia, or there was a marked
      recession of the total leucocyte count followed by a return of lymphocytes
      towards normal percentage. The blood picture indicated the conversion of an acute
      process into a subacute or chronic affair. These chickens survived for 78, 79 and
      110 days, respectively. An explanation for this occurred to us later when
      cultures recovered from them, instead of consisting of S colonies, showed the
      topography of the intermediate type, closely resembling the F.S. type. Evidently
      this was due to a reversion; i.e., a loss of virulence of the organism occurring
      within the animal body. At necropsy the spleen and liver were somewhat enlarged
      and contained prominent, discrete yellow nodules resembling small shot in their
      size and shape, which, in one case could be lifted from the tissue by the point
      of the knife. Microscopically, they possessed small centers of caseation
      surrounded by numerous giant cells and large mononuclear cells with a thick
      border of lymphocytic cells. This tubercle formation could not be classified in
      any special group as it was too sharply circumscribed and walled off by
      lymphocytic cells to be considered as truly malignant in nature as the S type of
      lesion. Even the younger tubercles in these cases, which consisted of clumped
      epithelioid cells with prominent lymphocytic cell borders, could not be called
      acute or "toxic" in character. At present we make only limited deductions from
      our observations. In the bacterial dissociation phenomenon we have at least a new
      line of investigation, and different variants of tubercle bacilli must be taken
      into consideration when planning new tuberculosis studies. With the stabilization
      of the human type variants, experiments such as reported here may bring about the
      proper clinical interpretation, of the course of human tuberculosis.

PMID- 19870130
TI  - FURTHER OBSERVATIONS ON THE USE OF PNEUMOCOCCUS EXTRACTS IN EFFECTING
      TRANSFORMATION OF TYPE IN VITRO.
AB  - Pneumococcus extracts highly active in inducing the in vitro transformation of
      the specific types of Pneumococcus have been prepared by dissolving S cells with
      sodium desoxycholate, precipitating the dissolved material in alcohol in which
      the bile salt remains soluble, and extracting the precipitate in salt solution.
      Further purification of these active extracts has been attained by the removal of
      considerable inactive material by charcoal adsorption and by reprecipitation of
      the adsorbed extract in alcohol or acetone. The importance of using young
      cultures for extraction, and of preventing autolysis during the preparation of
      the extracts, is emphasized. Extracts prepared by the method described have been
      filtered through Berkefeld Candles (V, N, and W) without appreciable loss in
      activity, provided the reaction of the extract was slightly alkaline at the time
      of filtration. The purified and filtered extracts are water-clear, and sterile by
      rigid cultural and animal tests. They have been heated to temperatures of 60
      degrees C. for 30 minutes without appreciable loss in their capacity to induce
      specific changes in type. And although they have generally shown definite
      decrease in potency after heating to temperatures above 80 degrees C., some
      extracts have been found active even after an exposure of 10 minutes to a
      temperature of 90 degrees C. They have been completely inactivated by boiling.
      Relatively small amounts of extract have been effective when added to a broth
      medium containing normal serum or serous fluid. In this medium, R pneumococci,
      irrespective of their type derivation, have developed and thereafter retained all
      the type-specific characteristics of the encapsulated S cells from which the
      extract was prepared. The specific action of the extracts is discussed with
      reference to their transforming and antigenic properties.

PMID- 19870131
TI  - CHANGES IN THE SHAPE AND SIZE OF BACTERIUM COLI AND BACILLUS MEGATHERIUM UNDER
      THE INFLUENCE OF BACTERIOPHAGE-A MOTION PHOTOMICROGRAPHIC ANALYSIS OF THE
      MECHANISM OF LYSIS.
AB  - This paper contains the records of a motion photomicrographic investigation of
      the lysis of Bact. coli and B. megatherium by bacteriophage. The bacteria mixed
      with bacteriophage were grown on moist nutrient agar in small culture chambers on
      the stage of a microscope in an incubator maintained at 37 degrees C. The
      apparatus used permitted continuous inspection of the preparations. Photographs
      were made at the rates of 2 and 30 per minute and at the rate of 8 per second
      during the terminal stage of lysis of Bact. coli. The accurately timed films were
      studied by rapid projection and by the projection of single frames. Measurements
      of dimensions of cells, calculations of volumes, information on generations,
      generation times and duration spans are presented in the tables. Similar
      information on normal cultures grown and photographed in the same way is
      furnished for comparison. Groups of serial photographs are reproduced in the
      plates to illustrate the special features observed. These observations seem to us
      to warrant the following conclusions: 1. Enlargement or swelling of the cells of
      Bact. coli usually, but not always, precedes lysis. Some of the enlargement is an
      expression of increase of cell substance and is not altogether due to imbibition
      of water. Cells of early generations of Bact. coli enlarge to greater absolute
      and relative proportions than cells of later generations. Enlargement does not
      occur before lysis in B. megatherium. 2. The terminal stage of lysis of Bact.
      coli is explosive, occupying (1/2) to (7/8) second. The terminal stage of lysis
      of B. megatherium is a slow disintegrative process, extending over 2-10 minutes.
      3. Bacteriophage inhibits fission of some cells, but does not stop the
      reproduction of other cells in contact with it. The genealogical records of six
      generations of cells of Bact. coli and of two generations of cells of B.
      megatherium indicate that bacteriophage may be transmitted through parents to the
      offspring which ultimately undergo lysis. 4. Bacteriophage spreads by contact
      through a group of cells and also along paths determined by genetical
      relationships. 5. A large amount of cellular debris remains after the lysis of
      the cells in both of these species of bacteria. This residue of material is in
      the form of irregularly shaped masses and granules. This material is not in
      solution at the time of lysis and appears not to be digested or hydrolized. 6.
      Theories of the mechanism of lysis are discussed. It is suggested that reduction
      of surface tension of the cells may be an important factor in the mechanism of
      lysis.

PMID- 19870132
TI  - STUDIES ON THE SUPRARENAL CORTEX : I. CORTICAL SUPRARENAL INSUFFICIENCY AND THE
      ACTION OF THE CORTICAL HORMONE UPON THE NORMAL AND SUPRARENALECTOMIZED DOG.
AB  - 1. The methods used in the operation and care of suprarenalectomized dogs are
      given. 2. The effect of injections of the cortical hormone upon normal and
      suprarenalectomized dogs is described. 3. Symptoms and chemical studies of
      suprarenal insufficiency in the dog, following extract withdrawal are described,
      together with the effects produced by its readministration. 4. The phenomena
      associated with experimental suprarenal insufficiency are contrasted with those
      seen in patients with Addison's disease. The identity of the acute symptoms with
      those of "shock" is pointed out.

PMID- 19870133
TI  - ENHANCED LETHAL EFFECTS OF X-RAYS ON BACILLUS COLI IN THE PRESENCE OF INORGANIC
      SALTS.
AB  - 1. When B. coli are irradiated by x-rays in a series of salt solutions of tenth
      molar concentration, the synergistic effect does not become appreciable until
      heavy salts are used. 2. When Pb(NO(3))(2) or KBr solutions are used in
      increasing concentrations, the synergistic effect is not appreciable until large
      concentrations or absorption coefficients are reached, whereupon the effect
      increases sharply. Thus the number of effective hits per bacterium per minute,
      alpha, is a function of the absorption coefficient, micro. 3. The sharp increase
      in alpha does not occur at the same concentration, or same micro, for
      Pb(NO(3))(2) and for KBr. Thus alpha is a function of the nature of the salt, or
      possibly of the penetration of the salt into the cell, some measure of which may
      be obtained from the initial toxicity of the solution. 4. For a given solution,
      alpha increases as the wave length lambda of the x-rays decreases, although micro
      decreases by the same process as the cube of lambda. Thus alpha is a function of
      lambda to some power greater than the cube. 5. A possible mechanism whereby the
      synergistic effect takes place is discussed briefly, as is the possibility that
      the heterogeneity of the x-rays accounts for all or part of the increased
      bactericidal effect of the rays in the presence of heavy metal salts. 6. Results
      indicate that within the range investigated, short wave lengths of x-rays, in
      conjunction with sensitizers, are the more efficacious in producing lethal
      effects.

PMID- 19870134
TI  - SOME EFFECTS OF ANTERIOR PITUITARY EXTRACTS ON NITROGEN METABOLISM, WATER
      BALANCE, AND ENERGY METABOLISM.
AB  - 1. Solutions of the globulin fraction of alkaline extracts of the anterior lobe
      of beef pituitary glands, when administered intraperitoneally or subcutaneously
      to dogs for 1 or 2 days, greatly increase the nitrogen balance. Urine nitrogen
      falls markedly, and at the same time blood non-protein nitrogen decreases, while
      the nitrogen of the feces remains the same. 2. The nitrogen gained may either be
      retained or lost again, indicating that it may be converted into reserve protein
      rather than into permanent structures. Sudden gains in weight which follow the
      injections are always lost again. 3. The effect of the extracts on protein
      catabolism is greatest when this is high, as in adult dogs having a negligible
      positive nitrogen balance, or a negative balance, while consuming a high protein
      diet adequate in calories. 4. Both the fall in nitrogen excretion, and the
      subsequent rise, when the latter occurs, are due to changes in urea excretion. 5.
      Other results of the brief treatments are: great increases in water intake and
      urine volume, marked thirst, slight rise in temperature, and a remarkable
      increase in heat production effected by oxidation of fat. Mature female dogs were
      used, and in one of these lactation occurred after some of the injections.

PMID- 19870135
TI  - NUTRITIONAL ENCEPHALOMALACIA IN CHICKS : INFLUENCE OF AGE, GROWTH, AND BREED UPON
      SUSCEPTIBILITY.
AB  - 1. Nutritional encephalomalacia may be induced in chicks up to the age of
      approximately 2 months. As the preliminary feeding period on a natural foods diet
      is increased, the percentage incidence of the disease becomes progressively less.
      The average time between institution of diet and appearance of the disease tends
      to diminish. 2. There is no correlation between growth and incidence of the
      disease. 3. White Leghorns, Barred Plymouth Rocks, Rhode Island Reds, and White
      Wyandottes are equally susceptible.

PMID- 19870136
TI  - STUDIES ON THE PRECIPITIN REACTION : PRECIPITATING HAPTENS; SPECIES DIFFERENCES
      IN ANTIBODIES.
AB  - 1. Partial hydrolysis products of the specific polysaccharide of Type III
      pneumococcus ranging from 550 to 1,800 in formula weight can be quantitatively
      freed from unhydrolyzed polysaccharide. 2. The fractions yield specific
      precipitates with Type III antipneumococcus horse serum but fail to precipitate
      homologous rabbit antisera, giving rise only to specific inhibition. The
      aldobionic acid, the structural unit of S III, does not precipitate antisera. 3.
      A possible explanation and a possible application of the findings are pointed
      out.

PMID- 19870137
TI  - STUDIES ON TYPHUS FEVER : X. FURTHER EXPERIMENTS ON ACTIVE IMMUNIZATION AGAINST
      TYPHUS FEVER WITH KILLED RICKETTSIA.
AB  - 1. Vaccines consisting of formalinized Rickettsiae of Mexican typhus fever,
      obtained by our X-ray rat method, produce definite resistance in guinea pigs to
      subsequent infection with the virus of this disease. 2. The resistance so
      produced amounts to complete immunity when the subsequent infectious dose is
      moderate-that is, consists of typhus blood or of tunica material in reasonable
      amounts (not more than one-quarter of a tunica-i.e., roughly 100 to 250
      infectious doses). When, as in the first experiment, excessive doses of
      infectious material were given, the vaccination protection was, in two of the
      three animals, incomplete. 3. Subcutaneous vaccination is fully as effective as
      intraperitoneal -even when the subsequent infection is intraperitoneal. 4. As in
      previously reported experiments, the vaccines made with the Mexican organisms
      conferred only partial and feeble protection against the European virus (Breinl
      strain).

PMID- 19870138
TI  - STUDIES ON TYPHUS FEVER : XI. A REPORT ON THE PROPERTIES OF THE SERUM OF A HORSE
      IMMUNIZED WITH KILLED FORMALINIZED RICKETTSIA.
AB  - The experiments recorded above demonstrate that the systematic treatment of a
      horse with formalin- and phenol-killed Rickettsiae obtained from the Mexican
      virus by our X-ray rat technique induces the development of properties in the
      horse's serum which may be described as follows: 1. An original agglutinating
      potency for Proteus X-19 (Weil-Felix reaction) not exceeding dilutions of 1-40
      was enhanced to a potency of 1-160 and, feebly, 1-320. 2. The horse's serum,
      after immunization, exerts distinct protective action against the Mexican virus,
      whether mixed with the virus before injection, administered 1 week or somewhat
      longer before the virus or given 24, 48 or 72 hours after infection with virus.
      Experiments of the last category have been most successful when the serum was
      given subcutaneously. 3. The serum of the immunized horse agglutinates the Weigl
      louse vaccines, containing Rickettsia prowazeki of the European disease in
      dilutions comparable in potency to the Weil-Felix reaction. Since the serum
      described exerted protective effects when given 7 and 13 days before infection
      with the virus, there is some prospect of prophylactic usefulness on the part of
      this serum. Since the serum also protected when subcutaneously administered 24,
      48 and 72 hours after intraperitoneal infection of guinea pigs, and somewhat
      modified the disease even when given 96 hours after infection-that is 1 day
      before the control came down with a typical reaction-, it is at least logical to
      investigate its possible therapeutic value by early administration in the human
      disease of the New World or Mexican type. The time intervals governing the
      experiments of the last two categories in guinea pigs were of course dependent
      upon the balance between the amounts of virus and of serum used. The failure of
      similar effects upon the European virus is not easily explained. This is
      especially difficult to understand in view of the unquestionable agglutinating
      potency of the serum for the Weigl vaccines. Whether this difficulty is purely a
      quantitative one, or depends upon other factors, can be determined only by
      further investigation.

PMID- 19870139
TI  - SPLENECTOMY IN BILE FISTULA DOGS : BILE PIGMENT OVERPRODUCTION, ANEMIA AND
      INTOXICATION.
AB  - A splenectomized dog can be kept anemic for months or years in perfectly good
      condition. A renal bile fistula dog on a suitable diet can be kept in perfect
      health and activity with normal weight for years. When we combine splenectomy and
      the bile fistula, after a latent period, we invariably observe a striking
      reaction with enormous over-production of bile pigment, a definite anemia and
      finally death from anemia or tissue hemorrhage. The spleen is essential for life
      in the bile fistula animal and this suggests some contribution from the spleen to
      body internal metabolism. The spleen and bile together are essential for the
      normal metabolism of pigment. The bile salts are suspected of playing some
      obscure role in this reaction. It seems difficult to explain all this great
      excess of bile pigment as coming from hemoglobin built up from the usual diet
      factors which in these experiments are well standardized. It is suggested that
      the body can synthesize the pyrrol aggregate (four pyrrol rings). There is some
      evidence that the liver can build up bile pigment direct from "building stones."
      It seems necessary to postulate one or the other mechanism and they do not seem
      unlike in the final analysis as both bile pigment and the pyrrol aggregate
      contain four pyrrol rings. Possibly both reactions may take place under these
      conditions.

PMID- 19870140
TI  - THE MANNER OF REMOVAL OF PROTEINS FROM NORMAL JOINTS.
AB  - 1. Data are presented showing that precipitin tests can be used for the detection
      of the proteins contained in egg white and horse serum in the blood stream and
      thoracic duct lymph following injection into the knee joints of normal dogs. The
      sera of rabbits immunized against the particular protein employed were used in
      doing the precipitin tests. 2. Egg white is removed only by way of the
      lymphatics, appearing more rapidly if the leg muscles are massaged. The removal
      is even greater from passively exercised joints. 3. Horse serum albumin is
      readily removed from a normal dog's knee joint by way of the lymphatics alone and
      with greater rapidity from a passively exercised joint. Horse serum globulin
      escapes from normal joints with great difficulty, if at all, and therefore does
      not readily gain entrance into the underlying lymphatic capillaries. 4. The
      molecular size of a protein readily gaining egress from a joint through the
      lymphatics is thus defined. 5. The relative sizes of the albumin and globulin
      molecules contained in horse serum are confirmed by in vivo experiments. 6. The
      lymphatic system is the essential apparatus for the removal of protein from
      joints, and any interference with this drainage should promote the formation of
      intraarticular effusion. The data presented suggest that a simple clinical test
      for determining the efficiency of the lymphatics draining a single joint can be
      devised.

PMID- 19870141
TI  - CELLULAR MECHANISMS OF RENAL SECRETION. A STUDY BY THE EXTRAVITAL METHOD : I. THE
      STRUCTURAL PHASE OF THE SECRETORY MECHANISM.
AB  - 1. The secretion of neutral red reproduces those variations which are observed in
      the mitochondrial apparatus of the renal tubule cells of animals living under
      native conditions. The tubular absorptive processes concerned with water, salts
      and sugars do not produce these effects. 2. The changes in the mitochondria
      consist of both structural and constituent alterations. These have been shown to
      be not merely phenomena concomitant with secretion, but a determining factor in
      one part of this process; namely, in the concentration of the dye within the
      cell.

PMID- 19870142
TI  - CELLULAR MECHANISMS OF RENAL SECRETION. A STUDY BY THE EXTRAVITAL METHOD : II.
      THE FUNCTIONAL PHASE OF THE SECRETORY MECHANISM.
AB  - 1. The elimination of neutral red by the renal epithelium is a composite process,
      consisting of a direct and an indirect secretion. 2. The mechanism controlling
      direct secretion is concerned with the permeability of the two cell membranes.
      These two membranes may be affected independently in the direction of either an
      increased or decreased permeability, with a corresponding increase or decrease in
      the elimination of the dye. 3. The mechanism controlling indirect secretion is
      concerned with the mitochondrial apparatus of the cell. By means of change in the
      form and constituent substance of its structures, the dye is concentrated within
      the cell and slowly eliminated. 4. Direct secretion, depending on the condition
      of sensitive membranes, is easily disturbed. Such disturbances account for the
      wide variations in the elimination of dye observed in the functioning of abnormal
      kidneys. Indirect secretion, depending on the simpler factor of the solubility of
      the dye in the protoplasmic constituents, continues even when the cells are
      severely damaged.

PMID- 19870143
TI  - A STUDY OF THE BACTERIAL CAPSULE BY NEW METHODS.
AB  - A new method for staining capsules is described. With this method appearances are
      produced about the somata of a number of non-capsulated organisms which resemble
      capsules.

PMID- 19870144
TI  - EPITHELIAL REPAIR IN RECOVERY FROM VITAMIN A DEFICIENCY : AN EXPERIMENTAL STUDY.
AB  - 1. In vitamin A deficiency, the replacement stratified keratinizing epithelium is
      morphologically identical in all locations. 2. All cells of the lowermost layer
      of the replacement epithelium have proliferative power as in the stratum
      germinativum of epidermis. 3. In recovery, in spite of the complete morphological
      masking, the epithelium in each region returns to its normal type. 4. The
      important histological features of repair involve removal of the layers of cells
      irreversibly differentiated towards keratinization and direct differentiation of
      the stratum germinativum into the normal type. These take place simultaneously.
      5. The histological sequences observed in the removal of cells above the stratum
      germinativum indicate that autolysis as shown by vacuolar degeneration and
      heterolysis as shown by leucocytic infiltration are involved. 6. The cycle of A
      deficiency metaplasia and recovery affords an experimental method available for
      the correlation of nuclear chromatin and types of cytoplasmic activities.

PMID- 19870145
TI  - AN ANALYSIS OF THE OPSONIC AND TROPIC ACTION OF NORMAL AND IMMUNE SERA BASED ON
      EXPERIMENTS WITH THE PNEUMOCOCCUS.
AB  - 1. In normal unheated human serum, virulent pneumococci may be prepared for
      phagocytosis by two separate antibodies, acting in conjunction with complement.
      One of these is the type-specific anticarbohydrate antibody reacting with the
      carbohydrate fraction of the pneumococcus. The other is probably also a type
      specific antibody, but quite distinct from the former, and therefore must react
      with a different antigenic constituent of the bacterium. 2. In the normal human
      serum heated to 56 degrees C., these two antibodies may, after prolonged contact
      with the organism, promote phagocytosis of the pneumococcus without the adjuvant
      action of complement. 3. Although these two antibodies are equally effective in
      the phagocytosis of 24 hour culture organisms by normal blood, the
      anticarbohydrate antibody tends to become the predominant factor as the
      pneumococci approach the state in which they exist in the animal body. 4. In so
      far as we have been able to show, the anticarbohydrate antibody is the only
      antibody in immune serum which can induce phagocytosis. This substance by itself
      is active in a phagocytic system, but just as in the normal serum, complement
      enhances its effect. The failure to demonstrate the presence in the immune serum
      of an antibody, distinct from the anticarbohydrate antibody, analogous to that
      found in the normal serum, may be due to the experimental difficulty of removing
      all the anticarbohydrate antibody from a concentrated immune serum. 5. Thus it is
      seen that a single well defined antibody (the anticarbohydrate antibody) may be
      responsible for the phagocytic action of normal unheated serum, normal heated
      serum, inactivated immune serum, and immune serum activated by complement. These
      facts appear to us to invalidate Neufeld's division of the phagocytic antibodies
      into (a) bacteriotropins (antibodies, the phagocytic titre of which is not raised
      by the addition of complement); (b) opsonic antibodies (antibodies, comparable to
      the lysins, which are only active in the presence of complement). 6. Complement
      alone is incapable of inducing phagocytosis of the pneumococcus. In the
      phagocytic process, it appears simply to increase the speed at which the reaction
      takes place. Its role may be compared to that of a catalyst in a chemical
      reaction. 7. On the basis of these findings, it is proposed that the term
      "tropin" be discarded as misleading and unnecessary, and that the term "opsonin"
      be retained to denote any heat-stable antibody which prepares bacteria for
      phagocytosis. Contrary to current usage, it would not suggest a combination of
      antibody with complement.

PMID- 19870146
TI  - STUDIES ON MENINGOCOCCUS INFECTION : I. BIOLOGICAL PROPERTIES OF "FRESH" AND
      "STOCK" STRAINS OF THE MENINGOCOCCUS.
AB  - Freshly isolated strains of meningococci present a number of characteristics
      which can be shown to differ not inconsiderably from those of stock strains long
      maintained on artificial media. Rough variants of the different types can be
      demonstrated, either arising spontaneously in vivo or in vitro, or evoked in the
      laboratory by the method described by Enders. Neither the freshly isolated
      strains-which are smooth- nor, in most cases, the rough variants of them are
      stable, both showing a tendency to pass over into the stock form or variant. The
      stock strains in the course of transformation from the freshly isolated strains
      show changes in morphology and cultural characteristics, and in viability in
      defibrinated blood.

PMID- 19870147
TI  - STUDIES ON MENINGOCOCCUS INFECTION : II. MONOVALENT DIAGNOSTIC SERA PREPARED FROM
      "FRESH" AND "STOCK" STRAINS.
AB  - The production of monovalent sera for agglutinin or precipitin reactions with
      freshly isolated strains of meningococci is described. Agglutination reactions
      with such sera can be carried out more rapidly, at lower temperatures and in
      lower dilutions, than with the standard monovalent sera prepared from stock
      cultures, while the results so obtained are more satisfactory owing to the
      relative absence of cross-agglutination.

PMID- 19870148
TI  - A SEROLOGICAL DIFFERENTIATION OF HUMAN AND OTHER GROUPS OF HEMOLYTIC
      STREPTOCOCCI.
AB  - 1. All except two of 106 strains of hemolytic streptococci isolated from man,
      other animals, milk, and cheese have been classified into five groups, which bear
      a definite relationship to the sources of the cultures. These broad groups may be
      subdivided into specific types by methods discussed elsewhere. The specific group
      classification is made possible by employing two special reagents: (a) extracts
      prepared by treatment of the bacteria with hot hydrochloric acid, and (b) serum
      of animals immunized with formalinized cultures. This differentiation is not
      detected by the agglutination reaction. The grouping agrees with that described
      by other investigators on the basis of cultural and biochemical characteristics.
      2. The group-specific substance present in strains of Group A has been identified
      chemically as carbohydrate in nature. The chemical composition of the specific
      substances upon which the specificity of the other groups depends has not been
      determined. It seems not unlikely, however, that all of them may belong in the
      general class of carbohydrates, each being chemically distinct and serologically
      specific in the individual groups.

PMID- 19870149
TI  - EXPERIMENTAL PRODUCTION OF PYLOROSPASM AND GASTRIC RETENTION IN RATS.
AB  - 1. A method was found whereby the development of gastric retention could be
      studied in intact animals without the necessity of recourse to the use of x-rays.
      2. Gastric retention was found to develop as a result of protein restriction in 7
      out of 10 rats studied. Such retention could again be cleared up with protein
      realimentation or by allowing the animals free choice of protein, fat and
      carbohydrate. 3. A diet high in protein following periods of undernutrition or
      prolonged protein restriction usually gave rise to a transient gastric retention.
      4. Diets with a solution of 25 per cent or more of alcohol added promptly gave
      rise to gastric retention in rats even when the protein content of the diet was
      adequate. 5. Evidence is given indicating that the gastric retention which
      occurred in this study involved more or less pylorospasm and the possible
      influence of mechanical and chemical irritation and of changes in gastric mucin
      and bile flow upon the development of pylorospasm are discussed. 6. Spira's
      theory that fat in the diet gives rise to pylorospasm and ulceration is not
      supported by the results of our experiments.

PMID- 19870150
TI  - THE VALUE OF THE SKIN TEST WITH TYPE-SPECIFIC CAPSULAR POLYSACCHARIDE IN THE
      SERUM TREATMENT OF TYPE I PNEUMOCOCCUS PNEUMONIA.
AB  - Skin tests were made with Type I S.S.S. in 53 cases of Type I pneumococcus lobar
      pneumonia, 48 of which were treated with antipneumococcus Type I serum. In all
      but 1 of the 46 recovered cases a positive, immediate skin reaction was obtained
      at about the time of recovery. In 7 fatal cases reactions were consistently
      negative, even in the presence of circulating type-specific antibodies. The skin
      test has proved to be an extremely valuable guide to serum therapy, and a
      definite prognostic aid. The test has distinct advantages over the agglutination
      reaction in that it is not merely an index of circulating antibodies. When
      positive, it invariably denotes that recovery has begun; when negative, it
      indicates further serum therapy. The mechanism of the positive skin test is
      closely related to that operative in recovery from pneumonia, and is apparently
      the resultant of antibody and tissue activity.

PMID- 19870151
TI  - ANAPHYLACTIC SHOCK BY AZODYES.
AB  - Experiments are described which show that anaphylactic shock can be induced in
      animals sensitized with azoproteins by injecting them with azodyes containing the
      same azo components as the sensitizing antigen. The anaphylactic reactions are
      specific and occur with quantities of the dyes as small as fractions of
      milligrams.

PMID- 19870152
TI  - HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER : I. NORMAL, INFECTION AND
      INTOXICATION.
AB  - Human liver tissue has been assayed to determine the concentration of hemoglobin
      production factors in normal and abnormal states. Standardized dogs made anemic
      by bleeding have been used in this biological assay and the human liver tissue
      compared with control animal tissue. Normal human liver tissue (external trauma)
      contains much more of these hemoglobin production factors than the normal control
      animal liver-the ratio being 162 to 100. In this form of biological assay 42 gm.
      of animal liver or 26 gm. of human liver represent 1 gm. of potential hemoglobin.
      A second group (Table 2) in which the viscera were practically normal except for
      atrophy, the cases presenting a good deal of arteriosclerosis and senile changes,
      shows a lower content of these hemoglobin production factors. The ratio of human
      to control here is 117 to 100. This is certainly the low limit of normal. Acute
      fulminant infections reduce somewhat the store of these potent hemoglobin
      production factors in the human liver (Table 3). The average value is 117 as
      compared with 100 control but the more acute cases show the lower values. Chronic
      intoxications show values which are close to the human normal-151 per cent. The
      liver content of hemoglobin producing factors shows very wide fluctuations in
      cases of thyrotoxicosis. Diabetes may be associated with rather low values. There
      may be complete dissociation of the organic iron content and the concentration of
      hemoglobin production factors in the liver.

PMID- 19870153
TI  - HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER : II. LIVER DEGENERATION,
      CANCER, CIRRHOSIS AND HEPATIC INSUFFICIENCY.
AB  - Biological assay of human liver material shows various concentrations of
      hemoglobin producing material in various diseased states. Cardiac congestion with
      red atrophy of the liver shows values (Table 21) somewhat below the human normal
      94 per cent compared to 162 per cent. It is probable that this is due to atrophy
      and destruction of the liver cells in the centers of the liver lobules. We
      believe the remaining liver cells have a normal content of hemoglobin producing
      factors. Amyloid (tuberculosis) and fatty (alcoholic) degeneration show (Table
      22) subnormal values-111 per cent compared to 162 per cent. If we allow for the
      "dilution" of liver cell weight by the amyloid and fat we observe normal values
      for the concentration of hemoglobin producing factors. Carcinoma growth in the
      liver whether primary or secondary shows net figures (Table 23) which are low-75
      per cent compared to normal 162 per cent. It appears that cancer tissue, even
      tumor cells originating from hepatic epithelium, contains no hemoglobin producing
      factors. If we allow for the "dilution" of the remaining liver cells by the
      cancer tissue the figures are within normal limits. Cirrhosis and hepatitis
      (Table 24) with no signs of true hepatic insufficiency or severe hepatic injury
      but death supervening from secondary infection or hemorrhage will give average
      normal values -164 per cent compared to normal human of 162 per cent. Icterus is
      not a factor. Cirrhosis or hepatitis with severe parenchyma injury and signs of
      hepatic insufficiency give low values (Table 25) in biological assay -48 per cent
      compared to normal human 162 per cent. It may be surprising that the liver cells
      hold so tenaciously to these unknown factors influencing hemoglobin production
      but obviously only in severe liver injury is this concentration seriously
      reduced.

PMID- 19870154
TI  - HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER : III. ANEMIAS-PRIMARY, APLASTIC
      AND SECONDARY-LEUKEMIAS.
AB  - Biological assay of the human liver in various types of anemia shows conspicuous
      differences in the concentration of hemoglobin producing factors. Pernicious
      anemia shows very high values and the liver in untreated cases may show maximal
      storage of the hemoglobin producing factors. Liver therapy reduces this store as
      the missing factor is supplied and new hemoglobin and red cells can be turned out
      by the marrow. Aplastic anemia likewise shows high concentration of hemoglobin
      producing factors as there is no outlet for this material through the red marrow.
      Secondary anemia due to loss of blood will show low normal values but even long
      standing severe anemia will not seriously deplete this store of hemoglobin
      producing factors in the liver. Secondary anemia due to blood destruction within
      the body shows higher values and some excess store of hemoglobin producing
      factors and iron. Leukemia gives a biological assay like secondary anemia due to
      blood loss and always presents definite anemia. Iron analyses show conspicuous
      differences and iron concentration within the liver parenchyma does not in any
      way parallel the concentration of hemoglobin producing factors. The highest
      values for iron concentration are found in aplastic anemia (70 mg. per cent)-
      high values in pernicious anemia (51 mg. per cent)-normal values in leukemia (13
      mg. per cent)-and low values in anemia due to loss of blood (5.3 mg. per cent).
      These findings should aid in a more complete understanding of the pathogenesis
      and internal metabolism of various anemias.

PMID- 19870155
TI  - THE EFFECT OF PROTEOLYTIC DIGESTION PRODUCTS ON MULTIPLICATION AND MORPHOLOGICAL
      APPEARANCE OF MONOCYTES.
AB  - It has been found that the enzymatic digestion products of proteins cause a rapid
      proliferation of blood monocytes in vitro. Digestion mixtures having anywhere
      from 12 to 68 per cent of their nitrogen in the amino form possess this property.
      For continued proliferation, heparin plasma or serum must be repeatedly supplied
      with the digests. Without them, multiplication continues for only a few days, the
      coagulum in which the cells are embedded liquefies around the central fragment,
      and the cells disintegrate. The enzymatic digests exert a marked effect on the
      morphological appearance of the cells and finally cause them to agglutinate. The
      extent of this effect is determined by the degree of hydrolysis of the digest,
      its concentration, and the length of time the cells are cultivated in it. The
      morphological appearance of the cells is also somewhat influenced by the nature
      of the plasma or serum used with the digest. Digests having very little free
      amino nitrogen produce short, round, granular cells. Those more highly hydrolyzed
      produce large, long, slender forms. An increase in the concentration of the
      digest in the medium causes a shortening and broadening of the cell and an
      increase in its granulations. Therefore, even a highly hydrolyzed digest may, if
      concentrated, give cells resembling those in a lower concentration of a less
      hydrolyzed one. The digests have a cumulative effect on the cells, as the time of
      cultivation is extended. Therefore, cultivation for a long period in a dilute
      solution may give the same effect as a shorter time in a higher concentration. A
      different effect is obtained if plasma is used with the digest than if serum is
      used, even when the plasma and serum are taken from the same animal. The
      monocytes cultivated in serum and digest are generally shorter, broader, and more
      granular than those cultivated in heparin plasma and digest. They also contain
      more fat and have a greater tendency to digest the clot. Agglutination of the
      cells takes place more readily in highly hydrolyzed products than in those
      slightly hydrolyzed. It is hastened by increase in concentration of the digest in
      the medium. It occurs more readily at the periphery of the culture and sooner in
      serum and digest than in heparin plasma and digest. Completely hydrolyzed
      proteins and mixtures of pure amino acids do not produce effects at all
      comparable to those of the enzymatic digests either in their effect on the rate
      of cell proliferation or their action on the morphology of the cell. Arsenic
      pentoxide in dilutions from 1:20,000 to 1:80,000 is the only other agent known to
      bring about agglutinations of the monocytes when cultivated in vitro. The early
      changes in the morphological appearance of the cell that are produced by these
      digests are reversible. When the digests are removed from the medium and the
      cells cultivated in plasma and Tyrode solution, they very gradually revert to
      their original form.

PMID- 19870156
TI  - THE EFFECT OF RESTRICTION OF PROTEIN INTAKE ON THE SERUM PROTEIN CONCENTRATION OF
      THE RAT.
AB  - Rats placed on a low protein diet for 21 weeks, in spite of marked loss of body
      weight, showed no significant decrease of serum protein concentration aside from
      an initial (physiological ?) drop.

PMID- 19870157
TI  - CHANGES IN BACTERIAL VOLUME AS THE RESULT OF SPECIFIC AGGLUTINATION.
AB  - Measurements indicate that bacterial antigens increase in volume as the result of
      specific agglutination. There is a general parallelism between the increase in
      antigenic volume and the concentration of the immune serum. The phenomenon is
      specific. There is no increase with normal serum; with absorbed serum the
      increase is slight and it can be correlated with the presence of unabsorbed
      antibody. The effect is enduring as shown by volumetric determinations upon
      repeatedly washed, agglutinated bacteria.

PMID- 19870158
TI  - THE SIGNIFICANCE OF CHANGES IN ANTIGENIC VOLUME AS THE RESULT OF SPECIFIC
      AGGLUTINATION.
AB  - Findings are described which amplify those of a preceding paper in showing that
      bacteria increased in volume when treated with specific agglutinin. When the
      increase in volume approximated 20 per cent all the bacteria were agglutinated.
      We have attempted to correlate the volumetric increase with the quantity of
      protein adsorbed by the organisms during agglutination and have studied not only
      bacteria but collodion particles first sensitized to antigen and then
      agglutinated with a precipitin specific for the antigen. The increase in volume
      of the collodion particles was small and the quantity of protein adsorbed
      relatively large. When two species of bacteria were agglutinated with their
      respective antisera the reverse was true; the apparent volume increase was much
      greater than the quantity of protein deposited during the reaction. There is,
      then, no direct correlation between protein deposition and apparent increase in
      volume. Nevertheless, the results of experiments here reported have suggested an
      explanation for the fact of increase in volume.

PMID- 19870159
TI  - FURTHER OBSERVATIONS ON THE CULTIVATION OF VACCINE VIRUS IN LIFELESS MEDIA.
AB  - We have made ten attempts to cultivate vaccine virus in tissue extracts prepared
      according to the method described by Eagles and Kordi (4). Renal, testicular, and
      chick embryo extracts were employed with a dermal strain of vaccine virus and
      with the Levaditi strain of neuro-vaccine virus. In no instance were we able to
      show that the virus multiplied in the extract media. Both of these strains of
      virus, however, multiplied in media containing bits of minced viable tissue.
      Furthermore, treatment of rabbit testicular tissue and chick embryo tissue in the
      manner described by Eagles and Kordi for the preparation of the extracts leaves
      some cells not only alive but capable of proliferation. Although the results of
      our work are not in accord with those obtained by Eagles and Kordi, we offer no
      explanation for the discrepancy. Nevertheless, one cannot examine the results of
      our work recorded in the six tables without recognizing the fact that in the
      types of media used the presence of viable cells appears to be essential for the
      multiplication of vaccine virus. Rabbit testicular tissue and bits of chick
      embryos support the regeneration of the active agent more efficiently than does
      rabbit renal tissue.

PMID- 19870160
TI  - THE LYMPHATIC PARTICIPATION IN HUMAN CUTANEOUS PHENOMENA : A STUDY OF THE MINUTE
      LYMPHATICS OF THE LIVING SKIN.
AB  - A technic is described for the demonstration of lymphatic capillaries in living
      skin and for their study. By means of vital dyes injected intradermally these
      vessels can be rendered plainly visible. They form an extraordinarily abundant
      anastomotic web. The least scratch, one which does not penetrate through the
      epidermis, gives rise to such conditions that lymphatic absorption readily takes
      place from the abraded surface; and so close-meshed is the lymphatic web that an
      intradermal injection with even the finest hypodermic needle tears some of the
      constituent vessels open with result that they undergo direct injection. In many
      individuals much of the fluid introduced at an ordinary intradermal injection,
      like that made in the clinic, spreads through the superficial lymphatic network,
      whereas in others it tends to enter the deeper lymphatics at once, the difference
      being due to merely physical factors determined by skin texture. Normal flow
      along the skin lymphatics is rapid even when the body is at rest, dye introduced
      into the skin of the resting forearm reaching the axilla within a few minutes.
      The observations make plain the fact that every intradermal injection is an
      intralymphatic one, often preponderantly such, while furthermore every local
      injection into the skin becomes within a few minutes a general one, so rapidly is
      the introduced material transported to the blood. The normal permeability of the
      skin lymphatics of man is approximately the same as that of the mouse. Tests
      indicate that in both instances the lymphatic wall behaves like a semipermeable
      membrane. The permeability of the human lymphatic wall like that of the mouse is
      subject to rapid and great changes. A stroke on the skin with a blunt instrument
      to produce a wheal, causes the lymphatic capillaries to become so permeable
      temporarily that dyes pass through their walls as if practically no barrier
      existed, instead of being held back for a greater or less period. Slight
      inflammation due to heat, ultraviolet light or bacterial products has a similar
      effect. So, too, has histamine. When fluid pours rapidly into the tissue from the
      blood, as when a wheal is formed, the lymphatics are compressed and their
      efficiency as drainage channels is interfered with. These facts are briefly
      discussed in their bearing upon skin phenomena in general. The lymphatics cannot
      be disregarded in considering such phenomena, in which it is plain that they have
      a large share.

PMID- 19870161
TI  - ELECTROLYTE BALANCE STUDIES IN ADRENALECTOMIZED DOGS WITH PARTICULAR REFERENCE TO
      THE EXCRETION OF SODIUM.
AB  - 1. Balance studies have been made on three dogs before and after adrenalectomy,
      performed in two stages. 2. It has been shown that the sodium concentration of
      the blood decreases in adrenalectomized dogs, as is true in patients suffering
      from Addison's disease and in cats experimentally adrenalectomized. 3. There are
      also decreases in the chloride and bicarbonate concentrations which together are
      approximately equivalent to the decrease in sodium. 4. An increase in the
      potassium concentration of the blood occurs after adrenalectomy, as reported in
      other studies. There is no obvious correlation of this change with changes in
      potassium balances. 5. The balance studies show a striking loss of sodium from
      the body during the development of adrenal insufficiency. This loss of Na results
      from an increased excretion of sodium in the urine and is not complicated by loss
      of base as a result of vomiting or diarrhea. 6. Following adrenalectomy, both the
      total amount of sodium and its concentration in the urine are markedly increased.
      This increase in concentration of sodium occurs in spite of an augmented urine
      volume. 7. The behavior of the chloride ion following adrenalectomy parallels
      that of the sodium ion, but the loss is not equivalent. 8. During the period of
      accumulation of non-protein nitrogen in the blood, the rate of water excretion by
      the kidney is even greater than before removal of the adrenal glands. 9. The
      possibility of a regulatory effect of the adrenal glands upon sodium metabolism
      and renal function has been discussed.

PMID- 19870162
TI  - INHERITED AND ACQUIRED FACTORS IN RESISTANCE TO INFECTION : I. DEVELOPMENT OF
      RESISTANT AND SUSCEPTIBLE LINES OF MICE THROUGH SELECTIVE BREEDING.
AB  - 1. A colony of inbred mice has been established free from inter-current
      infections and from the influence of extraneous variables detrimental to a study
      of their resistance to natural infection. A technique of measuring the resistance
      of mice to natural B. enteritidis mouse typhoid infection has been developed. 2.
      The Rockefeller Institute albino strain showed an average 37.4 per cent mortality
      to B. enteritidis mouse typhoid infection. 3. By breeding from progeny of mice
      dying early after exposure, lines approximately 85 per cent susceptible were
      obtained; by breeding from unexposed progeny of mice surviving infection, lines
      15 per cent susceptible were obtained. Further selection within the most
      susceptible and most resistant lines did not alter their reaction; selection
      within the less susceptible and less resistant lines increased the sought factor.
      These rates remained approximately the same when the susceptibles received
      1/100th and the resistants ten times the standard dose. The selected mice reacted
      consistently when exposed to spontaneous herd infection. 4. Several strains of
      mice, brother to sister inbred for special factors, did not differ materially in
      susceptibility. White-face and selected black-and-tan strains, however, proved
      89.0 and 97 per cent susceptible. 5. White-face susceptibles mated with resistant
      Rockefeller Institute mice gave F(1) progeny, 17.7 per cent susceptible. F(1)
      mice back-crossed to susceptibles gave progeny 61.2 per cent susceptible and back
      crossed with resistants gave progeny 26.3 per cent susceptible. F(2) mice mated
      inter se gave progeny 34.2 per cent susceptible. The results indicate that
      resistance factors are dominant and not sex-linked.

PMID- 19870163
TI  - INHERITED AND ACQUIRED FACTORS IN RESISTANCE TO INFECTION : II. A COMPARISON OF
      MICE INHERENTLY RESISTANT OR SUSCEPTIBLE TO BACILLUS ENTERITIDIS INFECTION WITH
      RESPECT TO FERTILITY, WEIGHT, AND SUSCEPTIBILITY TO VARIOUS ROUTES AND TYPES OF
      INFECTION.
AB  - 1. Mice with relatively great inherent resistance to certain bacterial infections
      were heavier but not more fertile than mice with relatively little inherent
      resistance. Mice with relatively little inherent resistance were with one
      exception not abnormally low in weight. 2. B. enteritidis given intrastomachally
      to susceptibles appeared in the blood stream more promptly, in larger numbers,
      and in a greater percentage of cases, and was present in feces in larger numbers,
      for a longer period, and in a greater percentage of cases than when given to
      resistants. 3. Mice relatively resistant to B. enteritidis administered by the
      natural gastrointestinal route were likewise resistant to the organisms
      introduced subcutaneously, intraperitoneally, and intravenously. Mice relatively
      susceptible to the organisms administered by the natural route were susceptible
      when the organisms were injected directly into tissues and blood stream. 4. Of
      four lines of mice relatively susceptible to B. enteritidis, three were likewise
      susceptible to Pasteurella avicida, B. friedlaenderi, and pneumococcus given
      intranasally. A fourth line was significantly more resistant. Lines of mice
      relatively resistant to B. enteritidis were likewise resistant to the three
      respiratory tract pathogens. 5. When Pasteurella avicida, B. friedlaenderi, and
      pneumococcus were injected intraperitoneally or intravenously, no significant
      differences in duration of life of the several lines of mice could be
      demonstrated. 6. Of four lines relatively susceptible to B. enteritidis, two were
      susceptible to an intranasal instillation of louping ill virus. Lines resistant
      to B. enteritidis proved relatively susceptible to the virus infection.

PMID- 19870164
TI  - A COMPARATIVE STUDY OF SUBCUTANEOUS NODULES IN RHEUMATIC FEVER AND RHEUMATOID
      ARTHRITIS.
AB  - The foregoing comparative study on the subcutaneous nodules in rheumatic fever
      and rheumatoid arthritis is presented as part of an investigation which has been
      conducted in this clinic on the relationship of the two clinical entities,
      rheumatic fever and rheumatoid arthritis. It is believed that the present study
      has shown that these lesions are highly characteristic of the two diseases and
      that they represent different phases of the same, fundamental, pathological
      process. However, it should be pointed out that the presence of closely related
      or even identical lesions in two, separate, clinical entities cannot be
      considered as valid evidence in support of the hypothesis that the two diseases
      are etiologically related. Comparative clinical studies on the relationship of
      rheumatic fever and rheumatoid arthritis will be presented in a succeeding
      communication. These studies, as well as serological investigations on the two
      diseases which have been reported elsewhere (23, 24), lend further support to the
      conception that rheumatic fever and rheumatoid arthritis are intimately related
      and possibly different responses of affected individuals to the same etiological
      agent.

PMID- 19870165
TI  - PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES IN ITS RELATION TO
      BACTERIAL HYPERSENSITIVENESS.
AB  - The observations reported in this paper demonstrate that the intravascular
      interaction of bacterial and animal protein antigens with homologous antibodies
      at the site of a tissue made vulnerable by bacterial filtrates induces prompt
      severe hemorrhagic necrosis in this tissue. In the light of these observations
      there is offered an explanation of the mechanism underlying focal and skin
      bacterial hypersensitiveness.

PMID- 19870166
TI  - STUDIES ON THE ETIOLOGY OF SPONTANEOUS CONJUNCTIVAL FOLLICULOSIS OF MONKEYS : II.
      BACTERIOLOGICAL EXPERIMENTS.
AB  - In the bacteriological study here reported, we undertook an investigation of the
      flora associated with spontaneous conjunctival folliculosis. Following the plan
      of Noguchi (2), monkeys and chimpanzees were inoculated with the different
      organisms recovered from affected tissues. By this means, we disclosed among the
      bacteria a new species, Bacterium simiae, which was found to be specifically
      active, in that it induced follicular reactions in the conjunctiva apparently
      indistinguishable from the disease as it occurs in nature. The specific action of
      the bacterium in animals is the more striking when it is compared with the
      innocuousness of other organisms isolated from cases of folliculosis, and also
      when considered in relation to the behavior of quarantined animals. While the
      disease arises spontaneously in stock animals, of some 300 normal rhesus monkeys-
      these being isolated in lots of ten to twenty and quarantined from 6 to 14 weeks
      not one has as yet shown folliculosis. With the insignificant exception already
      mentioned (1), the experimental disease was produced only when the inoculum
      contained either folliculosis tissue or cultures of the simian organism. Apart
      from these findings, the experimental results indicate that (a) the bacterium has
      thus far been recovered only from folliculosis cases and not from other forms of
      conjunctivitis nor from normal tissues; (b) the microorganism has been isolated
      not only from affected conjunctivae of stock monkeys but also from the tissue of
      animals- macaques and apes-experimentally infected with the bacterium, and (c)
      such recovered cultures have, in turn, been found to be specifically pathogenic
      in normal rhesus monkeys and chimpanzees. We may therefore postulate from this
      experimental study that an intimate relation exists between Bacterium simiae and
      spontaneous conjunctival folliculosis of simians.

PMID- 19870167
TI  - THE EFFECTS OF BLOOD LOSS AND BLOOD DESTRUCTION UPON THE ERYTHROID CELLS IN THE
      BONE MARROW OF RABBITS.
AB  - The relative proportion of the various sorts of erythroid cells of the bone
      marrow has been determined after acute and chronic hemorrhage and after damage to
      the marrow with acetyl phenylhydrazine. The normal erythroid pattern shows
      megaloblasts and erythroblasts in the lowest percentage, then normoblasts,
      reticulocytes, and mature erythrocytes respectively, in increasing proportions.
      All three states studied show an increasing "shift to the left" up to a condition
      after acetyl phenylhydrazine, in which the erythroblasts and megaloblasts exceed
      the mature erythrocytes. The marrow pattern finds direct expression in terms of
      the cells of the blood.

PMID- 19870168
TI  - THE HYPOPHYSEAL SUBSTANCE GIVING INCREASED GONADOTROPIC EFFECTS WHEN COMBINED
      WITH PROLAN.
AB  - The increased gonadotropic effect obtained by combining prolan with hypophyseal
      extracts can be secured equally well by the use of preparations which contain
      high amounts of the growth or of the gonad-stimulating hormone. In hypophyseal
      extracts containing the growth hormone, the synergistic effects do not parallel
      the content of growth-promoting substance. Similarly, in hypophyseal extracts
      containing the gonad-stimulating hormone, the synergistic effects do not parallel
      the content in the gonadotropic factor. The hypophyseal substance involved has
      been prepared sufficiently free of the growth and gonad-stimulating hormones to
      make it inadmissible to consider either of these substances as responsible for
      the reaction.

PMID- 19870169
TI  - THE REACTION OF STANDARD BREEDS OF RABBITS TO EXPERIMENTAL SYPHILIS.
AB  - A comparative study was made of the character and severity of the infection
      produced by Tr. pallidum in groups of standard bred Havana, Dutch, English,
      Himalayan, and Rex rabbits. All known variables that might influence the course
      of the disease were common to the different breed groups. On the basis of certain
      clinical data selected as criteria for the determination of variations in the
      response to syphilitic infection, it was found that the Havana and Dutch animals
      were resistant while the English, Himalayan, and Rex rabbits were susceptible.
      From these results, it appears that breed, race, or family is a factor which
      significantly influences the response to infection with Tr. pallidum.

PMID- 19870170
TI  - MODIFICATION OF THE PATHOGENICITY OF PSEUDORABIES VIRUS BY ANIMAL PASSAGE.
AB  - Pseudorabies virus, Iowa strain ("mad itch"), after passage through guinea pig
      brain, fails to produce infection in guinea pigs when injected subcutaneously
      unless enormous doses are employed. Such virus is still pathogenic for rabbits
      when given subcutaneously and for rabbits and guinea pigs intracerebrally.
      Comparison of the amounts of virus present in the brains of rabbits and guinea
      pigs following fatal cerebral infection shows that the latter contain, per gram,
      only approximately one-tenth the amount of virus in the former. Comparing the
      resistance of the two species to subcutaneously administered pseudorabies virus
      it has been found that rabbits are approximately 100 times more susceptible than
      guinea pigs. Over and above the working of these two factors, guinea pig passage
      appears to achieve some actual attenuation of virus when tested by subcutaneous
      inoculation into guinea pigs.

PMID- 19870171
TI  - LOCALIZATIONS OF THE VIRUS OF POLIOMYELITIS IN THE CENTRAL NERVOUS SYSTEM DURING
      THE PREPARALYTIC PERIOD, AFTER INTRANASAL INSTILLATION.
AB  - 1. About 4 days after intranasal instillation, the virus of poliomyelitis
      establishes its initial focus, within the central nervous system, in the
      olfactory bulbs. It apparently reaches this structure through the axons of the
      olfactory nerves after primarily infecting the olfactory cells of the nasal
      mucosa. 2. From this initial focus, the virus spreads (on the 5th and 6th days)
      through the olfactory tracts and their connections in the brain stem. A secondary
      focus in the hypothalamus is first established. From this, two main channels can
      be discerned: first, to the medulla; second, to the thalamus and midbrain. 3. On
      the 7th day, virus can first be detected in the spinal cord. It is widespread but
      is found in larger amounts in the cervical than in the lumbar segments. It is
      present in both the anterior and posterior horns, either in equal amounts or in
      slightly larger amounts in the posterior. It is also present in the
      intervertebral ganglia. The surmise is presented that the main route of infection
      of the cord is not from the medulla (which had been infected as early as the 5th
      day) but along the sensory tracts, presumably from the thalamus (spinothalamic
      tracts). 4. Certain portions of the central nervous system were never found to
      contain demonstrable quantities of virus: these were the cortex of the frontal
      and parietal lobes (neopallium), and the cerebellum. The olfactory (archipallial)
      cortex (hippocampus) was only once found to contain virus; this occurred on the
      7th day and in small amounts, and presumably had its source in the olfactory
      bulbs. 5. The experiments of the 7th day suggest that virus had died out in areas
      previously infected (in the hypothalamus and thalamus, particularly), while
      continuing, apparently undiminished, in the midbrain and medulla, and spreading
      to the cord. These observations are in harmony with the general contentions of
      Fairbrother and Hurst that virus is better adapted to survival in the lower
      portions of the cerebrospinal axis than in the higher. 6. The conception here
      presented of the manner of entrance and routes of propagation of the virus of
      poliomyelitis in the experimental animal appears to be in essential agreement
      with the clinical and pathological characteristics of the disease in man. Both
      the experimental disease and the disease as it occurs in man appear to present
      the features of an infection spread through nervous tissue only. It is
      unnecessary to assume that at any stage of its progress, during the incubation
      period or later, systemic or general extranervous infection is present.

PMID- 19870172
TI  - OBSERVATIONS ON THE IMMUNOLOGICAL RELATION OF POLIOMYELITIS TO LOUPING ILL.
AB  - The results of the work presented in the present paper show that louping ill and
      poliomyelitis immunologically are not closely related. Although relatively few
      experiments were performed, the data obtained were sufficiently decisive for our
      purposes. Certainly nothing was found to indicate that one might be able to
      immunize human beings against poliomyelitis by the use of louping ill virus. In
      addition to the negative findings, a certain amount of useful information was
      also secured, namely, (1) monkeys can be solidly immunized against louping ill by
      intraperitoneal injections of virus and partially protected by intramuscular
      administrations of the active agent, (2) during the process of immunization no
      signs of involvement of the central nervous system are manifested, and (3) sera
      from monkeys immunized in the manner described contain antibodies capable of
      neutralizing the virus.

PMID- 19870173
TI  - OXYCEPHALY AND ALLIED CONDITIONS IN MAN AND IN THE RABBIT.
AB  - Craniosynostosis and the pathological complex with which it is associated in the
      rabbit are not identical with the abnormalities seen in man; but apparently the
      two sets of conditions have enough in common to warrant the conclusion that they
      probably have a common mode of origin. The evidence so far obtained shows that in
      the rabbit these conditions are hereditary. The factors for the production of the
      cranial abnormalities are widespread, but the occurrence of deformities is
      comparatively rare in a general animal population. In-breeding and selective
      matings, however, tend to increase their frequency and also the frequency of
      other abnormalities with which they may be associated, either by chance or by
      close genetic relationship in the germ plasm. In this way, a pathological complex
      is built up and perpetuated. In so far as the cranial abnormalities are
      concerned, it seems now that oxycephaly and related conditions are variations
      resulting from a displacement or division of primary ossification centers
      controlled by hereditary factors.

PMID- 19870174
TI  - STUDIES ON INFLAMMATION : IX. A FACTOR IN THE MECHANISM OF INVASIVENESS BY
      PYOGENIC BACTERIA.
AB  - Trypan blue injected into an area of cutaneous inflammation induced by
      Staphylococcus aureus failed to drain readily to the tributary lymphatics when
      the dye was injected as early as 1 hour after the inoculation of the
      microorganisms. Trypan blue introduced into an area of cutaneous inflammation
      induced by Pneumococcus Type I was retained in situ when the dye was injected
      about 6 or more hours after the inoculation of the bacteria. When an area of
      cutaneous inflammation was induced by the inoculation of a culture of
      Streptococcus hemolyticus, trypan blue injected into it drained readily to the
      tributary lymphatics for the first 30 hours following the onset of the
      inflammatory reaction. When the inflammation had lasted for 45 hours or longer,
      the dye was fixed in situ and failed in most instances to reach readily the
      tributary lymphatics. The rapidity of fixation of the dye in the instances given
      would appear to depend on mechanical obstruction in the form of both a fibrinous
      network and thrombosed lymphatics or thrombosed lymphatics alone at the site of
      inflammation. Inasmuch as staphylococci, pneumococci, and streptococci spread
      from the site of cutaneous inoculation primarily through lymphatic channels, the
      difference in the rapidity with which mechanical obstruction is set up in the
      areas inflamed by them will help to explain the differing invasive abilities of
      these pyogenic organisms.

PMID- 19870175
TI  - EXPERIMENTAL GRANULOPENIA, DUE TO BACTERIAL TOXINS ELABORATED IN VIVO.
AB  - Pyogenic organisms, under conditions simulating a focal infection, are capable of
      producing in rabbits a granulopenia which may allow generalized infection and
      death. It is suggested that agranulocytosis in man is due to the action of
      leucocidin, rather than to a specific microorganism.

PMID- 19870176
TI  - STUDIES ON THE SUPRARENAL CORTEX : II. METABOLISM, CIRCULATION, AND BLOOD
      CONCENTRATION DURING SUPRARENAL INSUFFICIENCY IN THE DOG.
AB  - 1. The basal oxygen consumption, respiratory quotient, blood flow, blood
      pressure, and the changes in concentration of the arterial blood were determined
      in suprarenalectomized dogs (a) when receiving injections of cortical extract
      (Swingle-Pfiffner), (b) during suprarenal insufficiency induced by withdrawal of
      the injections, and (c) during the period of recovery brought about by resumption
      of extract injections. 2. Reasons are advanced for the view that the
      hemoconcentration which occurs is probably due to loss of fluid through the
      kidneys, rather than by increased capillary permeability and loss into the
      tissues, or by loss through the gastrointestinal tract. 3. The loss of fluid from
      the plasma and tissues will explain the symptoms which follow withdrawal of
      injections of the hormone, as well as the fatal outcome. The assumption that the
      suprarenal cortex or its hormone has a detoxifying action upon some product of
      metabolism is thus rendered unnecessary.

PMID- 19870177
TI  - STUDIES ON THE PREVENTION OF CHOLESTEROL ATHEROSCLEROSIS IN RABBITS : I. THE
      EFFECTS OF WHOLE THYROID AND OF POTASSIUM IODIDE.
AB  - 1. Whole thyroid gland when administered simultaneously with cholesterol
      prevented the atheromatous changes produced by the latter in the aorta of rabbits
      in 17 of 19 animals. 2. In this series thyroxin was less effective, as
      atherosclerosis occurred in 8 of 11 rabbits. 3. Potassium iodide also exerted a
      strong protective action as aortic lesions were present in only 1 of a series of
      12 rabbits fed cholesterol and potassium iodide concurrently. 4. The
      effectiveness of potassium iodide was not shared by potassium bromide or
      potassium chloride. 5. A relationship was noted between the level of the
      cholesterol in the blood and the development of atherosclerosis. In general, the
      aortic lesions accompanied a hypercholesterolemia.

PMID- 19870178
TI  - STUDIES ON THE PREVENTION OF CHOLESTEROL ATHEROSCLEROSIS IN RABBITS : II. THE
      INFLUENCE OF THYROIDECTOMY UPON THE PROTECTIVE ACTION OF POTASSIUM IODIDE.
AB  - 1. Thyroidectomy in itself does not cause a rise in blood cholesterol or the
      development of atherosclerosis in young rabbits. 2. Feeding cholesterol produces
      hypercholesterolemia and atherosclerotic lesions in rabbits regardless of the
      presence or absence of the thyroid glands. 3. Potassium iodide prevents the usual
      hypercholesterolemia and atherosclerosis of the aorta in normal rabbits fed
      cholesterol, but when the thyroids are removed this protective action disappears.

PMID- 19870179
TI  - STUDIES ON THE SUPRARENAL CORTEX : III. PLASMA ELECTROLYTES AND ELECTROLYTE
      EXCRETION DURING SUPRARENAL INSUFFICIENCY IN THE DOG.
AB  - A characteristic alteration in the electrolyte structure of the blood plasma of
      the suprarenalectomized dog occurs when injections of cortical extract are
      stopped. This alteration progresses during the course of the suprarenal
      insufficiency, parallel with the hemoconcentration and the loss in weight. When
      injections of cortical extract are resumed, the electrolyte structure returns to
      its original form, the alterations paralleling the dilution of the blood and the
      return of the body weight to its original level. The hemoconcentration, with the
      resulting physiological changes which take place in the suprarenalectomized dog
      after the cessation of cortical extract injections, is associated with a loss of
      sodium and chloride, accompanied by their proper complement of body water, by way
      of the kidney. Since this effect is produced in the suprarenalectomized animal,
      well nourished and in excellent condition, solely by cessation of injections of
      the cortical hormone, and since the reverse process of repair of the electrolyte
      and water losses can be effected solely by resumption of extract injections, it
      follows that all of the observed phenomena are due to this cause, and to this
      alone. It can be concluded that one function of the cortical extract in the
      suprarenalectomized dog is that of participation in the regulation of the sodium
      and chloride metabolism, and consequently, of the balance and distribution of
      water. The loss of water, in the absence of the cortical hormone, is sustained
      partly by the blood plasma, but to a far greater extent by the interstitial body
      fluid. The available evidence points to the kidney as the locus of this
      regulatory function of the cortical hormone.

PMID- 19870180
TI  - OBSERVATIONS ON ATTEMPTS TO PRODUCE ACUTE DISSEMINATED ENCEPHALOMYELITIS IN
      MONKEYS.
AB  - No evidence was found to support the idea that vaccine virus placed in the
      cisterna magna is capable of producing an acute disseminated encephalomyelitis
      with perivascular demyelination either in normal or in partially immune monkeys.
      A testicular extract (Reynals' factor) did not induce vaccine virus to cause an
      acute disseminated encephalomyelitis in monkeys. Repeated intramuscular
      injections of brain extracts and brain emulsions into eight monkeys were followed
      in two instances by an inflammatory reaction, accompanied by demyelination, in
      the central nervous system. The exact relation of the injections to the disease
      of the nervous system is not clear. The combined action of vaccine virus and an
      emulsion of fresh rabbit brain did not lead to the production of an acute
      disseminated encephalomyelitis in monkeys that had received repeated
      intramuscular injections of emulsions and alcohol-ether extracts of normal rabbit
      brains.

PMID- 19870181
TI  - THE ANTIGENIC RELATIONSHIP BETWEEN PROTEUS X-19 AND TYPHUS RICKETTSIAE : A STUDY
      OF THE WEIL-FELIX REACTION.
AB  - 1. The absorption of typhus sera (human or antityphus horse serum) with Proteus X
      19 removes only the Proteus agglutinins, leaving the Rickettsia agglutinins
      intact. 2. The absorption of typhus sera with Mexican Rickettsiae removes the
      agglutinins for both the Rickettsia and Proteus X-19. 3. While normal or
      formalinized Rickettsiae are not agglutinated by anti-Proteus serum, these
      organisms-when formalinized and heated at 75 degrees C.-become agglutinable by
      such serum. 4. The absorption of anti-Proteus serum with Mexican Rickettsiae
      removes agglutinins for formalinized and heated Rickettsiae but does not affect
      those for Proteus X-19.

PMID- 19870182
TI  - THE FORM AND FUNCTION OF SYNOVIAL CELLS IN TISSUE CULTURES : I. MORPHOLOGY OF THE
      CELLS UNDER VARYING CONDITIONS.
AB  - A detailed description is given of the various forms assumed by synovial cells in
      tissue cultures under varying conditions. A discussion of correlation between
      different morphologic appearances and certain functions of the cells is deferred
      until the end of the next paper (17).

PMID- 19870183
TI  - THE FORM AND FUNCTION OF SYNOVIAL CELLS IN TISSUE CULTURES : II. THE PRODUCTION
      OF MUCIN.
AB  - 1. Synovial cultures are differentiated in tissue cultures from other tissues of
      mesenchymal origin by their type of growth and cell function. 2. In these
      respects they are more closely allied to chondroblasts and osteoblasts than to
      fibroblasts. 3. Synovial cells in tissue cultures develop marked globular
      cytoplasmic granulations that stain easily with neutral red and sometimes with
      toluidine blue; they show marked polymorphism with all transitions from round to
      spindle, polygonal and star shapes and eventually form an epithelial-like
      membrane, composed of cells with numerous syncytial bridges. 4. In cultures of
      typically growing synovial cells a mucin-like substance is elaborated. Typical
      growth and maximal mucin production is best maintained in media containing a
      minimum of growth-stimulating substances. Transformation of synovial cell growths
      into fibroblastic growth is accompanied by a loss of mucin production. Dying
      cells apparently do not produce mucin. 5. Amitotic cell division and the
      formation of macrophage-like cells were observed. 6. Marked tendency to
      liquefaction of the plasma about the growths was observed and attributed to the
      elaboration of a proteolytic ferment. 7. The specific designation "synovioblasts"
      is proposed for these cells.

PMID- 19870184
TI  - THE RACES THAT CONSTITUTE THE GROUP OF COMMON FIBROBLASTS : II. THE EFFECT OF
      BLOOD SERUM.
AB  - 1. Under appropriate conditions, fibroblasts are able to multiply in serum, at a
      slow rate, for very long periods. 2. The rate of multiplication of fibroblasts in
      a given sample of serum depends entirely upon the nature of the strain. Cell
      races endowed with a high residual growth energy multiply more rapidly in serum
      than those whose growth potencies are of a lower order. 3. Fibroblasts, in the
      beginning, multiply more abundantly in plain serum than in heparinized serum, and
      also more abundantly in heparinized serum than in herparinized plasma. Later,
      these differences become less pronounced. 4. The first effect of serum on
      fibroblasts is invariably injurious, the degree of injury differing according to
      the nature of the cell strain and the age of the animal from which the serum is
      derived. With the passage of time, however, the colonies undergo gradual
      improvement, both in the appearance of the component cells and in their rate of
      proliferation. 5. In media containing embryonic tissue juice, or other growth
      activating substances, fibroblasts form colonies that are isomorphic and composed
      of isomorphic cells. In serum, fibroblasts form colonies of heteromorphic
      appearance. Each colony becomes composed of cells that differ from one another,
      to a more or less marked degree.

PMID- 19870185
TI  - QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION : ANTIBODY PRODUCTION IN RABBITS
      INJECTED WITH AN AZO PROTEIN.
AB  - 1. The preparation is described of a deep red protein dye, R-salt-azo-benzidine
      azo-crystalline egg albumen, which contains no more than traces of protein with
      the original egg albumen specificity. 2. Based on previous publications of the
      writers, a quantitative method is given for the micro estimation of precipitin in
      the antisera to the dye. The method gives the actual weight of precipitin and may
      be applied to the determination of the maximum amount of precipitable antibody in
      any antiserum. 3. Data are given (1) on the influence of the period between the
      final injection and the bleeding on the precipitin content of rabbit antisera to
      the azo protein; (2) on the magnitude of the antibody response following the
      injection of multiple doses of the antigen varying within wide limits; (3) on the
      variations in the precipitin content of the sera of rabbits given successive
      courses of antigen injections; and (4) on the stability of antisera stored in the
      cold. 4. Four antisera were obtained in which over 100 times as much precipitin
      was recovered as the amount of antigen injected. This supplements the growing
      mass of evidence against the theory that specific antigen fragments are actually
      incorporated into the antibody molecule.

PMID- 19870186
TI  - THE EFFECT OF PNEUMOCOCCUS AUTOLYSATES UPON PNEUMOCOCCUS DERMAL INFECTION IN THE
      RABBIT.
AB  - In pneumococcus dermal infections in rabbits, the addition of pneumococcus
      autolysate to an infective inoculum favors the invasiveness of the particular
      strain employed, but does not alter the kind of virulence possessed by that
      strain. Autolysates exhibiting this enhancing property also induce purpura in
      mice and inhibit the coagulation of rabbit blood. The relation of these
      properties to the infectivity of Pneumococcus and the possible role of bacterial
      autolysis in natural infection are discussed.

PMID- 19870187
TI  - STUDIES ON A CERTAIN SPREADING FACTOR EXISTING IN BACTERIA AND ITS SIGNIFICANCE
      FOR BACTERIAL INVASIVENESS.
AB  - Invasive strains of staphylococcus and streptococcus contain a soluble factor
      which markedly increases tissue permeability and enhances the infections produced
      by these organisms, by other bacteria, and by vaccine virus as well. The non
      invasive strains of the same species of staphylococci and streptococci do not
      contain this factor. The enhancing substance elaborated locally by organisms
      passes into the circulating blood and bringing about a general increase of tissue
      permeability may act to enhance local infections elsewhere. The factor is similar
      in the phenomena it elicits to the spreading factor extracted from many animal
      tissues, especially from testicle.

PMID- 19870188
TI  - THE EVALUATION OF ACTIVE RESISTANCE TO PNEUMOCOCCUS INFECTION IN RABBITS.
AB  - The dermal pneumococcus infection has been employed to determine the active
      resistance of rabbits against infection, and an evaluating scale of the gradient
      of resistance has been established. The significance of the various degrees of
      resistance has been discussed, and the possible general inferences of the
      findings indicated.

PMID- 19870189
TI  - RESISTANCE TO PNEUMOCOCCUS INFECTION IN RABBITS FOLLOWING IMMUNIZING INJECTIONS
      OF HEAT-KILLED PNEUMOCOCCUS SUSPENSIONS.
AB  - The degree and duration of the active resistance against pneumococcus infection
      have been determined in rabbits which received intravenous injections of a heat
      killed suspension of pneumococci of the three principal types. The resistance
      induced by the immunization procedure varied in degree and in duration with each
      type of Pneumococcus.

PMID- 19870190
TI  - THE TITRATION OF YELLOW FEVER VIRUS IN STEGOMYIA MOSQUITOES.
AB  - Titrations were made of yellow fever virus in stegomyia mosquitoes, using rhesus
      monkeys as test animals. It was found that: (a) The average mosquito immediately
      after engorging on highly infectious blood contained between 1 and 2 million
      lethal doses of virus. The titer of freshly ingested blood was as high as 1
      billion lethal doses of virus per cubic centimeter. (b) During the fortnight
      succeeding a meal on infectious blood there occurred a reduction of titratable
      virus to not more than 1 per cent of that present in the freshly fed insects. (c)
      The titer was somewhat higher at later periods. This rise in titer signified
      possibly not a multiplication, but merely an increase of extracellular virus and
      of that easily freed by grinding to a titratable form. (d) At no later stage did
      the quantity of titratable virus equal that demonstrable in freshly fed insects.

PMID- 19870191
TI  - VACCINATION WITH HEAT-KILLED AND FORMALINIZED TUBERCLE BACILLI IN EXPERIMENTAL
      TUBERCULOSIS.
AB  - 1. Rabbits vaccinated with tubercle bacilli killed by exposure to formalin (0.4
      per cent) did not show any acquired resistance to subsequent infection with
      bovine tubercle bacilli, while rabbits vaccinated with tubercle bacilli which had
      been killed by heating to 70 degrees for 1 hour survived more than half as long
      again as their controls. 2. Intraperitoneal injection of either the formalin
      killed vaccine or the heat-killed vaccine into guinea pigs made them skin
      sensitive to tuberculoprotein MA-100. 3. The rate of absorption of the formalin
      killed vaccine when introduced beneath the the skin was similar to that of the
      heat-killed vaccine. 4. Following the intravenous injection of heat-killed
      tubercle bacilli, it was found that rabbits developed a massive tubercular
      pneumonia. A study of the production and ultimate absorption of the cellular
      exudate showed that these processes were similar to those found after the
      injection of living bacilli. The lesions which followed the injection of heat
      killed bacilli differed from the lesions found in active tuberculosis in that in
      any one animal they showed a striking uniformity in appearance, while in the
      active disease the lungs showed a great diversity in type of lesion. Studies of
      the blood cells during the period of injection of dead organisms showed that the
      changes which are characteristic of the period during which a tuberculous
      pneumonia develops in rabbits (30 to 40 days after inoculation) were faithfully
      reproduced. It is suggested that the process of regression described may be
      similar to that which occurs in childhood tuberculosis, in which rather extensive
      pulmonary lesions resolve without leaving evidence of damage to the parenchyma of
      the lung.

PMID- 19870192
TI  - A STUDY OF THE THERAPEUTIC MECHANISM OF ANTI-PNEUMOCOCCIC SERUM ON THE
      EXPERIMENTAL DERMAL PNEUMOCOCCUS INFECTION IN RABBITS : III. THE INFLUENCE OF NON
      SPECIFIC FACTORS.
AB  - The purpose of the present investigation was to determine whether or not non
      specific agents were capable of exerting any influence on the response of
      pneumococcus-infected animals to specific serum therapy. It has been demonstrated
      in these experiments that whereas gold (empirically chosen) by itself had very
      little effect either on the course or the outcome of the experimental
      pneumococcus infection, it is nevertheless capable of exerting a definite and
      marked beneficial effect in rabbits treated with a subeffective dose of the
      specific antiserum. Of the rabbits treated with the subeffective dose of serum
      alone, 71 per cent died and only 29 per cent survived; the additional
      administration of gold reversed this death-survival ratio with the result that of
      a large group of rabbits which received the combined therapy, 77 per cent
      survived and only 23 per cent died.

PMID- 19870193
TI  - CHANGES IN THE TITER OF ANTIPNEUMOCOCCAL HUMORAL IMMUNITY IN ADULT HUMAN BEINGS.
AB  - Fifty-five individuals were tested to determine the pneumococcidal promoting
      activity of their serum against Types I and II pneumococci. By repeated tests an
      attempt was made to study the constancy of the degree of their immunity over
      intervals of 2 to 6 months. In this group were included nine persons with common
      colds and twelve cases of a severe influenza-like infection. Fifteen of the fifty
      five cases showed a change in titer of their humoral immunity against either Type
      I or Type II or both. Three of these showed an increase, and twelve a decrease.
      This reaction in most instances was a specific one in that the altered reaction
      toward one type was not associated with a similar change toward the other type
      pneumococcus. Colds and influenza-like infections apparently exerted no effect
      upon the titer of humoral immune substances.

PMID- 19870194
TI  - LYMPHOMATOSIS, MYELOMATOSIS, AND ENDOTHELIOMA OF CHICKENS CAUSED BY A FILTERABLE
      AGENT : I. TRANSMISSION EXPERIMENTS.
AB  - A new transmissible strain of leukosis of chickens is described that causes (a)
      lymphomatosis with or without tumor formation, and with or without leukemia, (b)
      myelocytomatosis with or without leukemia, and (c) endothelioma. All these
      diseases are transmissible by material free from viable cells, and the available
      evidence indicates that they are caused by a single filterable agent.

PMID- 19870195
TI  - VARYING HEMOLYTIC AND CONSTANT COMBINING CAPACITY OF STREPTOLYSINS; INFLUENCE ON
      TESTING FOR ANTISTREPTOLYSINS.
AB  - Certain properties of streptolysin in respect of hemolytic power and capacity for
      combining with antistreptolysins have been determined. The hemolytic strength may
      vary markedly, while under suitable conditions the combining power is constant.
      This stability of combining capacity makes it possible to prepare a large amount
      of streptolysin, standardize it against sera of known antistreptolysin strength,
      and use it as a reagent over a considerable period for testing the
      antistreptolysin content of unknown sera. A modified technique for making these
      tests is described.

PMID- 19870196
TI  - STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL : I. THE ISOLATION OF A
      BACILLUS WHICH PRODUCES A NASAL DISCHARGE.
AB  - By a method combining filtration and cultivation an unidentified Gram-negative
      bacillus was isolated from the nasal exudate of fowl experimentally infected with
      an uncomplicated coryza. Isolation was accomplished by cultivation on sealed
      blood agar plates after unsuccessful attempts to produce colonies on open plates.
      Injection of the organism into the palatine cleft of normal birds was regularly
      followed by an inflammation of the nasal mucosa and a discharge from the nares. A
      para-influenza bacillus which was also recovered from the nasal tract of affected
      fowl was innocuous. Certain cultural characters of the bacillus, bearing on its
      classification, are discussed.

PMID- 19870197
TI  - STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL : II. THE RELATION OF THE
      "BACILLARY" CORYZA TO THAT PRODUCED BY EXUDATE.
AB  - Three types of an uncomplicated fowl coryza, differing in the onset and duration
      of symptoms, developed after the intranasal injection into normal birds of
      exudate from natural cases. Protection tests were carried out with 2 of the types
      in an attempt to explain why the "bacillary" disease regularly ran a shorter
      course than the "exudate" disease. Reciprocal protection was demonstrated in one
      case, but in the other the birds which had recovered from the "bacillary" disease
      were susceptible to reinfection with exudate. There was no indication, however,
      that a second infectious agent was present in the exudate, and the failure to
      cross-immunize was ascribed, rather, to a reduction in the immunizing properties
      of the specific bacillus induced by artificial cultivation. It was also noted
      that the coryzas produced by exudate and bacilli, respectively, could be
      transmitted from infected birds to normal ones by direct contact. In both cases 1
      bird out of 5 failed to contract coryza on exposure. These 2 birds were later
      injected with the respective agents to which they had been exposed and found to
      be resistant.

PMID- 19870198
TI  - EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : THE EFFECT OF A PRIMARY INFECTION ON
      CONTACT TUBERCULOSIS IN RABBITS.
AB  - 73 per cent of normal rabbits exposed for about 1 year to cage mates infected
      with tubercle bacilli of bovine type acquired a respiratory or alimentary
      tuberculosis, which was fatal in 50 per cent of the cases. 63.6 per cent
      developed tuberculosis during the first 6 months. Of rabbits vaccinated with
      tubercle bacilli of human type and exposed in the same cages at the same time
      only 36.8 per cent acquired tuberculosis during the first 6 months. Later this
      resistance waned, and by the end of the year altogether 60 per cent had developed
      tuberculosis, of which 38 per cent succumbed. The disease in the vaccinated
      rabbits was shown to be of exogenous origin by the isolation in pure culture from
      the same rabbit of the human type bacillus from the primary infection, and of the
      bovine type bacillus from the naturally acquired lesion. The vaccination reduced
      the incidence, extent, and mortality of the disease, affected the route of
      infection, changed its pathological character, and retarded its progress. The
      disease acquired by vaccinated rabbits shared many characteristics with adult
      type tuberculosis in man. It is suggested that this method may be used with
      relative ease in studying many phases of naturally acquired tuberculosis in small
      laboratory animals.

PMID- 19870199
TI  - THE RESISTANCE OF RABBITS TO TUBERCULOSIS AFTER VACCINATION WITH PARTIALLY
      DEFATTED TUBERCLE BACILLI.
AB  - 1. A vaccine prepared from partially defatted bovine tubercle bacilli influenced
      favorably the survival time after inoculation with living virulent bovine
      tubercle bacilli. 2. Accompanying this increased resistance was a sustained
      lymphocytosis in the vaccinated animals. 3. The vaccine induced a transitory
      anemia and leucopenia. 4. A similar preparation of partially defatted human
      tubercle bacilli possessed the power to sensitize guinea pigs to tuberculo
      protein.

PMID- 19870200
TI  - STUDIES ON MENINGOCOCCUS INFECTION : III. THE ANTIGENIC COMPLEX OF THE
      MENINGOCOCCUS-A TYPE-SPECIFIC SUBSTANCE.
AB  - Three fractions have been isolated from autolysates of the meningococcus. Of
      these, one, the type-specific substance, has been described in detail. The same
      type-specific substance appears to be present in Type I and Type III organisms,
      but a substance differing at least serologically has been obtained from Type II
      strains. Detailed chemical analysis of both of the type-specific substances thus
      far isolated is being carried out and will be the subject of a later paper.

PMID- 19870201
TI  - STUDIES ON MENINGOCOCCUS INFECTION : IV. THE ANTIGENIC COMPLEX OF THE
      MENINGOCOCCUS-GROUP-SPECIFIC CARBOHYDRATE AND PROTEIN FRACTIONS.
AB  - Two group-specific substances, one a polysaccharide and the other a protein, have
      been isolated from the meningococcus and their serological properties are
      described. A discussion of these substances, together with the type-specific
      fraction, is given, and a relationship of these substances to certain serological
      phenomena is suggested.

PMID- 19870202
TI  - STUDIES ON MENINGOCOCCUS INFECTION : V. THE PRESENCE OF MENINGOCOCCUS
      PRECIPITINOGENS IN THE CEREBROSPINAL FLUID.
AB  - Precipitin tests, carried out on the cerebrospinal fluid from cases of
      meningococcal meningitis with monovalent sera, demonstrate the presence in that
      fluid of type-specific precipitinogens of the meningococcus. Negative results are
      secured when the spinal fluid is obtained after the commencement of intrathecal
      serum treatment and also occasionally when the numbers of infecting organisms are
      very small. The reaction offers an easy and rapid method of ascertaining to which
      type of meningococcus a particular case of meningitis is due, and facilitates the
      immediate use of monovalent therapeutic antimeningococcal serum. Typing by means
      of the precipitin reaction can be confirmed by agglutination of the strain of
      organism responsible for the infection, if such strain be isolated. Confirmation
      by means of agglutination has been possible in all the cases discussed in this
      report. Spinal fluids from other diseases of the meninges and central nervous
      system fail to give any precipitin reaction with the monovalent sera.

PMID- 19870203
TI  - EXPERIMENTAL AND STATISTICAL EVIDENCE OF THE PARTICULATE NATURE OF THE
      BACTERIOPHAGE.
AB  - Experimental evidence is brought forward to show that the bacteriophage obeys
      very closely the laws of chance distribution of particles in suspension.

PMID- 19870204
TI  - FUNCTION OF THE GALL BLADDER EPITHELIUM AS AN OSTEOGENIC STIMULUS AND THE
      PHYSIOLOGICAL DIFFERENTIATION OF CONNECTIVE TISSUE.
AB  - Evidence is presented that the proliferating gall bladder epithelium in the dog
      and guinea pig is capable of stimulating bone formation in certain connective
      tissues such as the abdominal wall. Other connective tissue areas such as the
      subepithelial connective tissue of the gall bladder and urinary bladder do not
      share in this tissue reaction and resist the bone stimulus of the epithelium. The
      formation of bone in these circumstances is thus biphasic. A difference between
      connective tissues morphologically identical can be proven physiologically, by
      their response to the osteogenic stimulus of appropriate epithelia. Calcium
      carbonate microliths occurred in the mucus of the occluded gall bladder in which
      there was transplanted connective tissue forming part of the wall.

PMID- 19870205
TI  - THE RACES THAT CONSTITUTE THE GROUP OF COMMON FIBROBLASTS : III. DIFFERENCES
      DETERMINED BY ORIGIN OF EXPLANT AND AGE OF DONOR.
AB  - 1. Races of fibroblasts that are functionally distinct have been isolated from
      the various tissues and organs of a single chick embryo. 2. Functionally distinct
      races of fibroblasts have also been isolated from corresponding parts of embryos
      of different ages. 3. Under the conditions of the experiments, and for the
      particular races of fibroblasts that have been studied, it has not been possible
      to demonstrate a gradual decrease, or a gradual increase, in the rate of
      multiplication of fibroblasts obtained from corresponding parts of embryos of
      gradually increasing ages. 4. Experiments made on strains of fibroblasts derived
      from the mesonephros and metanephros of a 16 day chick embryo have indicated that
      the rate of multiplication of these cells in a given medium reflects the
      physiological state, at the moment of isolation, of the particular part of the
      embryo from which they are obtained. 5. The rate of multiplication of a given
      race of fibroblasts in a particular medium does not serve, necessarily, as an
      index of the age of the individual from which the race is derived. 6. The
      functional differences that distinguish the various races of fibroblasts are
      permanent; they are retained by the cells from passage to passage indefinitely,
      despite such attempts as have thus far been made to change them.

PMID- 19870206
TI  - STUDIES ON PSEUDORABIES (INFECTIOUS BULBAR PARALYSIS, MAD ITCH) : I. HISTOLOGY OF
      THE DISEASE, WITH A NOTE ON THE SYMPTOMATOLOGY.
AB  - The histology of pseudorabies differs materially in various animal species. In
      the rabbit, subcutaneous, intradermal or intramuscular inoculation leads to local
      inflammation and necrosis. The infection ascends the peripheral nerve (possibly
      both interstitially and by the axis-cylinders) to the corresponding spinal
      ganglia and segments of the spinal cord, where primary degeneration of nerve and
      glial cells takes place. The nerve cell changes are probably responsible for the
      cardinal symptom of the disease, itching. Death ensues soon after virus reaches
      the medulla, before visible changes have been produced here. Intracerebral
      inoculation is followed by characteristic lesions in the meninges, in subpial
      glial cells and in superficially placed nerve cells. Morbid changes in the lungs
      are not necessarily related to the presence of virus, but specific lesions may be
      present. Intranuclear inclusions bearing some resemblance to those in herpetic
      encephalitis, yellow fever, etc., occur in cells derived from all embryonic
      layers. The disease in the guinea pig resembles closely that in the rabbit and is
      modified only by the slightly greater resistance of the animal. In the monkey
      after intracerebral inoculation, widespread degeneration and necrosis of cortical
      nerve cells are accompanied by the appearance of specific nuclear alterations in
      nerve and glial cells, but not in cells of mesodermal origin. No lesions are
      found in other viscera. In the spontaneous disease in the cow lesions approximate
      more closely to those in the monkey than to those in the rabbit. In the pig
      vascular and interstitial lesions predominate, nerve cell degeneration is
      relatively slight and typical inclusions are not observed. These differences
      probably explain the benign course of the malady following subcutaneous
      inoculation in this animal. The lymphatic system, too, participates in the
      reaction to the virus.

PMID- 19870207
TI  - SOME OBSERVATIONS ON THE SPECIFICITY OF BACTERIAL ALLERGY TO CERTAIN OF THE
      NEISSERIAE.
AB  - By means of the reaction to intracutaneous inoculation with bacterial suspensions
      in amounts of 0.2 cc., bacterial allergy was demonstrated in rabbits into which
      had been implanted agar foci containing either gonococci, meningococci, M.
      catarrhalis, or Bact. lepisepticum. The criterion of hypersensitiveness was the
      relative size and intensity of reaction evoked by an identical dose in "agar
      focus" and control rabbits. Rabbits sensitized to gonococci or meningococci
      usually reacted indistinguishably to either of these organisms, but were less
      allergic to M. catarrhalis. Similarly, animals sensitized to M. catarrhalis gave
      moderate but not maximal responses to the two former organisms. Cross-reactions
      did not occur between Bact. lepisepticum and any of the three Neisseriae. Animals
      sensitized to the four organisms mentioned reacted no more intensely than did
      controls to hemolytic streptococci, staphylococci, and rough pneumococci. The
      hypersensitive state was found to begin early in the 2nd week and to end usually
      by the 4th week, being at its height in most instances on the 10th to 12th days.
      The number of organisms contained in the agar focus determined the success of the
      sensitization only to this extent, that very small and very large inocula failed
      to evoke the allergic state. Rabbits immunized by intravenous injection of live
      organisms developed cutaneous reactions indistinguishable from those in controls.
      The "secondary rise" of Andrewes, Derick, and Swift was rarely observed.

PMID- 19870208
TI  - FURTHER STUDIES ON THE INFLUENCE OF TESTICLE EXTRACT UPON THE EFFECT OF TOXINS,
      BACTERIA, AND VIRUSES, AND ON THE SHWARTZMAN AND ARTHUS PHENOMENA.
AB  - The lesions produced by the Shwartzman and Arthus phenomena, as well as those
      produced by bacterial toxin and foreign sera in the normal rabbit, are spread by
      testicle extract over a larger area than would normally take place. With this
      spreading of the lesions there is a definite reduction in their intensity.
      Lesions produced by invasive strains of staphylococcus at high dilutions or non
      invasive staphylococci at moderate dilutions are definitely lessened in severity
      or even suppressed by the spreading action of testicle extract. Virus lesions are
      consistently enhanced by the spreading factor regardless of the dilution.

PMID- 19870209
TI  - INTRANASAL VIRULENCE OF PNEUMOCOCCI FOR MICE.
AB  - 1. Smooth colony pneumococci fresh from human beings, instilled in small doses
      into the nasal passages of special mice raised under standard conditions, brought
      about a characteristic infection and this spread to healthy contacts inciting in
      them the carrier state or fatal infection. 2. Differences in individual host
      response to the same dose of a given culture ranged from a complete refractory or
      nasopharyngeal carrier state, or a local cervical lymphadenitis, to fatal lobular
      or lobar pneumonias with or without pleurisy, empyema, and pericarditis, and
      acute fatal septicemia. 3. Pneumococci exhibited consistent individual strain
      differences with respect to ability to infect, when instilled intranasally into
      mice, and also differences in the spread to contacts. Degree of intranasal
      virulence paralleled demonstrable ability to spread to contacts. 4. Degree of
      intranasal virulence of strains did not parallel intraperitoneal virulence in 50
      per cent of strains-high intranasal was accompanied by either high or moderate
      intraperitoneal virulence, and low intranasal by high, moderate, or low
      intraperitoneal virulence. 5. Type III strains were of relatively high intranasal
      and intraperitoneal virulences; Type II strains mostly low in intranasal but high
      or moderate in intraperitoneal virulence; Type I strains all low in intranasal
      but either high or moderate in intraperitoneal virulence. Most strains of other
      types were low both in intranasal and intraperitoneal virulences. 6. The
      intranasal virulence of pneumococci was not enhanced by animal passage. Nasal
      passage reduced the intranasal virulence to zero but did not affect
      intraperitoneal virulence, colony form, and agglutinative specificity. Passage by
      the intraperitoneal method maintained the characteristic level of intranasal
      virulence for a period, increased intraperitoneal virulence in some instances,
      but did not affect colony form or agglutinative properties.

PMID- 19870210
TI  - THE FIBRINOLYTIC ACTIVITY OF HEMOLYTIC STREPTOCOCCI.
AB  - Broth cultures of hemolytic streptococci derived from patients are capable of
      rapidly liquefying normal human fibrin clot. The active fibrinolytic principle is
      also contained in sterile, cell-free filtrates of broth cultures. The degree of
      activity of filtrates parallels the activity of whole broth cultures sufficiently
      closely to indicate that large amounts of the fibrinolytic substance are freely
      excreted into the surrounding medium and pass readily through Berkefeld V, Seitz,
      and Chamberland filters. The occurrence of fibrinolysis is most strikingly
      observed when plasma or fibrinogen is mixed with active cultural material before
      clot formation is effected. Under the standard experimental conditions described,
      complete dissolution of human plasma clot (whole oxalated plasma + CaCl(2))
      occurs in about 10 minutes; complete dissolution of human fibrinogen clot
      (chemically isolated fibrinogen + thrombin) takes place in about 2 minutes.
      Titration of filtrate activity is recorded in Table IV. Twenty-eight strains of
      Streptococcus hemolyticus, isolated from patients suffering from various
      manifestations of streptococcus infection, have been tested for the capacity to
      liquefy fibrin clot. Broth cultures of all of the strains induced fibrinolysis.
      Of 18 strains of Streptococcus hemolyticus of animal origin, only three were
      capable of causing dissolution of clot. Completely negative results were obtained
      with 38 strains of other bacterial species. The list is presented on pages 492
      and 493. The plasma of many patients recovered from acute hemolytic streptococcus
      infections, when clotted in the presence of active cultures, is highly resistant
      to fibrinolysis. Furthermore, serum, derived from patients whose plasma clot is
      resistant, often confers on normal plasma clot an antifibrinolytic property. One
      example of the resistance possessed by the blood of convalescent patients is
      presented in this report. A second paper, now in preparation, will give in detail
      a large number of observations on the relation of infection to the development of
      resistance to the fibrinolytic activity of hemolytic streptococci. In contrast to
      the susceptibility of normal human fibrin clot to liquefaction by active culture,
      normal rabbit fibrin clot is totally resistant to dissolution when tested under
      comparable conditions. The insusceptibility of rabbit fibrin clot is manifest
      provided the coagulum is composed of rabbit constituents. When human thrombin is
      used to clot rabbit plasma or fibrinogen in the presence of active cultures,
      fibrinolysis is not prohibited. The role of thrombin in determining the
      resistance or susceptibility of rabbit fibrin to dissolution offers a suggestive
      approach to problems relating to the underiving mechanism.

PMID- 19870211
TI  - THE RELATION OF VITAMIN C DEFICIENCY TO INTESTINAL TUBERCULOSIS IN THE GUINEA
      PIG.
AB  - 1. Seventy-two adult guinea pigs were fed tuberculous sputum daily for periods
      ranging from 6 weeks to 4 months. 2. Thirty-seven of these were maintained on a
      diet partially deficient in vitamin C; twenty-six developed ulcerative intestinal
      tuberculosis. 3. In the remaining thirty-five animals whose diet was supplemented
      by an adequate amount of vitamin C only two developed tuberculous ulcers in the
      intestines. 4. From these studies we conclude that the ingestion of tubercle
      bacilli by the guinea pig is not the sole factor in the production of intestinal
      tuberculosis. 5. In our opinion, an adequate supply of vitamin C usually protects
      the guinea pig against ulcerative intestinal tuberculosis.

PMID- 19870212
TI  - A COMPARATIVE STUDY OF RECENTLY ISOLATED HUMAN STRAINS AND A PASSAGE STRAIN OF
      POLIOMYELITIS VIRUS.
AB  - 1. Confirmation of the qualitative differences which exist between so called
      human and passage strains of poliomyelitis virus has been established by the
      following observations. (a) The experimental disease induced by two human strains
      usually failed to protect monkeys against a subsequent infection by a passage
      strain, and in the few instances in which the reverse experiment could be tried a
      similar lack of protection was observed. (b) In some human sera the neutralizing
      power for a human strain differed qualitatively from the neutralizing power for a
      passage strain. 2. The time interval between the intracerebral inoculation of
      heterologous strains has been found to be an important factor bearing upon the
      results of the reinoculation experiments reported. Within the intervals used, the
      greater the period between the original infection and the reinoculation with a
      heterologous strain, the less was the degree of cross-immunity observed.

PMID- 19870213
TI  - NEUTRALIZING ANTIBODIES IN ABORTIVE POLIOMYELITIS.
AB  - The neutralizing antibody content for poliomyelitis virus has been tested with
      both a human and a passage strain of the virus in serial samples of sera from
      five mild cases of abortive poliomyelitis, and an increase in this antibody
      content has been demonstrated in convalescent samples obtained within 4 weeks of
      the acute illness.

PMID- 19870214
TI  - FURTHER STUDIES ON THE HYPOPHYSEAL SUBSTANCE GIVING INCREASED GONADOTROPIC
      EFFECTS WHEN COMBINED WITH PROLAN.
AB  - The hypophyseal substance-the synergic factor-which gives increased gonadotropic
      effects when combined with prolan has been shown to itself possess a definite
      though slight gonadotropic activity. It produces transitory follicular
      enlargement within 24-48 hours, which, however, regresses at once on cessation of
      treatment so that by the end of the 4th day the ovary again approximates its
      infantile weight. The synergic principle indeed provokes only moderate ovarian
      development when administered in 100 times the dose necessary to demonstrate the
      activation phenomenon. By means of isoelectric precipitation or by means of
      tryptic and ereptic digestion, fractions containing the synergic principle were
      freed of many contaminants, in particular of the antagonistic factor. The
      synergic principle has been shown to be unaffected by digestion with trypsin or
      trypsin followed by a short digestion with erepsin, but the action of pepsin
      inactivated the material. A preparation of the active substance has been obtained
      which is potent in a total dose of 27 gamma.

PMID- 19870215
TI  - THE RECOGNITION AND COMPARISON OF PROLAN AND PROLAN-LIKE SUBSTANCES.
AB  - The synergism phenomenon has made possible the recognition of substances, which
      we have called "prolan-like," in a wide variety of conditions. Indeed, it has
      been possible to demonstrate a prolan-like material in the urine of normal men.
      The method has shown a wide distribution of prolan-like substances in sera and
      urines of non-primates without demonstrating, however, significant difference in
      the reactions secured from pregnant as contrasted with non-pregnant states, or in
      males as contrasted with females. The synergism phenomenon with pregnancy prolan
      can also be shown in the increased development of the seminal vesicles of
      immature male rats. However, such males cannot be advantageously employed in the
      detection of prolan-like gonadotropic substances occurring in the blood and urine
      in conditions other than pregnancy, for the prolan-like substances usually do not
      effect appreciable development of the seminal vesicles.

PMID- 19870216
TI  - CONCENTRATION OF THE GONADOTROPIC HORMONE IN PREGNANT MARE'S SERUM.
AB  - The gonadotropic hormone of the blood of the pregnant mare has been greatly
      concentrated by adsorption on active aluminum hydroxide followed by elution. The
      preparations so obtained gave demonstrable gonadotropic effects within 100 hours
      in 21 day old female mice following three subcutaneous injections of 0.001 mg. in
      1 cc. of physiological saline. As is well known, other gonadotropic substances do
      not cause conspicuous development of the male gonads but injections of
      comparatively large doses of these preparations into immature male rats caused
      marked development of the testes, which in 10 days were trebled in weight. An
      astonishing increase in the weight of the seminal vesicles resulted, for these
      organs were approximately 75 times heavier than in controls.

PMID- 19870217
TI  - THE CULTIVATION OF MONOCYTES IN FLUID MEDIUM.
AB  - Monocytes from blood and from spleen have been cultivated in fluid medium in
      Carrel flasks for over 2 months. Diluted serum supplied all the essential
      nutritive substances. Cultivation in fluid was made possible by adjusting the
      initial pH of the fluid to 7.4, and not allowing it to fall below 7.0 or 6.8. The
      cells remained in good condition when the pH was adjusted with either lactic
      acid, hydrochloric acid, or carbon dioxide. Adjustment with carbon dioxide was
      found to be more convenient and also more practical, since it does not destroy
      the buffer action of the medium. After 2 months of cultivation, the monocytes
      were in excellent condition and still proliferated actively. They gave every
      indication that indefinite multiplication could be maintained under the
      conditions of these experiments. It is hoped that this method of cultivation,
      with some modifications, will prove useful in studying the metabolism of these
      cells.

PMID- 19870218
TI  - THE PRODUCTION IN DOGS OF CHRONIC BLACK TONGUE WITH ANEMIA.
AB  - 1. By the feeding of a particular diet, apparently lacking a substance closely
      associated with vitamin B(2) G, a chronic disease may be produced irregularly in
      dogs. 2. The disease is characterized by atrophic glossitis, diarrhea, loss of
      weight, and anemia. 3. The disease can be prevented and relieved by materials
      rich in vitamin B(2) G.

PMID- 19870219
TI  - INFECTIOUS PAPILLOMATOSIS OF RABBITS : WITH A NOTE ON THE HISTOPATHOLOGY.
AB  - A papilloma has been observed in wild cottontail rabbits and has been found to be
      transmissible to both wild and domestic rabbits. The clinical and pathological
      pictures of the condition have been described. It has been found that the
      causative agent is readily filtrable through Berkefeld but not regularly through
      Seitz filters, that it stores well in glycerol, that it is still active after
      heating to 67 degrees C. for 30 minutes, but not after heating to 70 degrees C.,
      and that it exhibits a marked tropism for cutaneous epithelium. The activities
      and properties of the papilloma-producing agent warrant its classification as a
      filtrable virus. Rabbits carrying experimentally produced papillomata are
      partially or completely immune to reinfection and, furthermore, their sera
      partially or completely neutralize the causative virus. The disease is
      transmissible in series through wild rabbits and virus of wild rabbit origin is
      readily transmissible to domestic rabbits, producing in this species papillomata
      identical in appearance with those found in wild rabbits. However, the condition
      is not transmissible in series through domestic rabbits. The possible
      significance of this observation has been discussed. The virus of infectious
      papillomatosis is not related immunologically to either the virus of infectious
      fibroma or to that of infectious myxoma of rabbits.

PMID- 19870220
TI  - AN IMMUNOLOGICAL STUDY OF NATIVE, DENATURED, AND REVERSED SERUM ALBUMIN.
AB  - Native and reversed horse serum albumin are indistinguishable when tested
      immunologically by means of the precipitin reaction.

PMID- 19870221
TI  - FURTHER OBSERVATIONS ON THE CULTIVATION OF VACCINE VIRUS FOR JENNERIAN
      PROPHYLAXIS IN MAN.
AB  - A dermal strain of vaccine virus has been passed through 99 successive culture
      passages. This procedure led to a diminution in the pathogenicity of the active
      agent for the rabbit. By repeated testicular passages in rabbits, however, the
      virus regained its pathogenicity for that host. New cultures were initiated with
      the revived virus. A culture strain of virus that has been twice revived in this
      manner has remained fairly stable for the rabbit through 60 culture passages and
      it produces mild, yet effective vaccinal reactions in man. Virus in early
      cultures was not attenuated for man, but later cultures of the original strain
      and cultures of the 2nd and 3rd revived strains produced mild reactions without
      fever and discomfort to the patients. Intradermal vaccinations with the culture
      virus are safe and satisfactory. With the culture virus 118 infants and children
      have been inoculated and in 100 of them a positive reaction occurred. The culture
      virus produced a refractory state to a standard dermal strain of calf lymph and
      vice versa. Culture virus stored in 50 per cent neutral glycerol at -10 degrees
      C. or at +3 degrees C. maintained a considerable amount of its activity for at
      least 1 year. Desiccated culture virus sealed in tubes maintained some of its
      activity when stored at 37 degrees C. for 5 weeks. Fresh cultures can be
      initiated without difficulty from desiccated virus or from virus that has been
      stored with or without glycerol.

PMID- 19870222
TI  - METHODS AND EFFECTS OF INCREASING THE URINARY CONSTITUENTS IN THE BODY.
AB  - 1. Five methods for the production of slow continued reabsorbtion of urine in the
      experimental animal are presented. 2. The effects of this prolonged reabsorption
      of urinary constituents on the blood chemistry and tissues are shown with special
      reference to the kidney. 3. Large and rapid increase of urinary constituents in
      the body is definitely destructive to the kidney. 4. The degenerative changes
      found in the experimental animal in the protected pole of the kidney showing
      nephritis produced by x-ray and in man in the unscarred portions of the kidney
      showing chronic nephritis account for the progressive nature and final renal
      insufficiency of these conditions and are best ascribed to the high levels of
      excretory products in the body.

PMID- 19870223
TI  - CULTIVATION OF PSEUDORABIES VIRUS.
AB  - Pseudorabies virus has been cultivated in series in rabbit testicle, guinea pig
      testicle, and chick embryo media, and its growth requirements have been studied.
      Intranuclear inclusions, similar to those produced by pseudorabies virus in vivo,
      have been found in rabbit testicle cultures. The virus has not changed its
      pathogenic properties for rabbits, guinea pigs, or mice during the course of
      cultivation.

PMID- 19870224
TI  - THE ACTION OF TYPE-SPECIFIC HEMOPHILUS INFLUENZAE ANTISERUM.
AB  - In this communication, further evidence has been given which supports the view
      that the majority of the strains of Hemophilus influenzae giving rise to
      meningitis are of the same serological type. Forty strains have now been
      examined, and thirty-seven have been of Type b. A horse has been artificially
      immunized with Type b strains isolated from the spinal fluid of patients. By
      precipitation tests with the capsular carbohydrate, the serum has been shown to
      be highly typespecific. For the first 3(1/2) months of immunization, the type
      specific antibody content of the serum increased steadily. Later, in spite of
      continued immunization, there occurred no apparent increase. By means of animal
      inoculations, it has been shown that the anti-serum has an anti-infectious
      action. If mice, inoculated intraperitoneally with Type b organisms, were also
      given serum, the bacteria did not invade the blood, or did so to only a limited
      degree. But the recovery of the treated mice was found to be inconstant. In
      rabbits infected intravenously and later treated by the same route, the number of
      bacteria in the blood stream was quickly reduced and sterilization followed. In
      the experiments it was necessary that the dosage of the culture be not too large,
      as influenza bacilli contain a substance which, artificially introduced into mice
      and rabbits, gives rise to marked toxic reactions. This substance is apparently
      not neutralized by the antiserum. However, it was found that among the surviving
      animals, those treated with immune serum returned to the normal state more
      quickly than did the animals not so treated. The anti-infectious action of the
      serum has further been demonstrated by a study of its effect on the lesions which
      follow inoculations of type-specific bacteria into the skin of rabbits. Again it
      was found that for any effect of the serum to be manifested it is necessary that
      the dosage of bacteria be limited, since if large numbers of bacteria are
      introduced into the skin the development of lesions cannot be completely
      inhibited, no matter how large doses of serum are employed. As the number of
      living S organisms which cannot be neutralized is roughly equivalent to the
      number of R or heat-killed bacteria which may produce a lesion, it seems that
      there is some preformed irritating substance in the bacterial cells which may
      give rise to lesions, even if the bacteria are killed or inhibited in their
      growth. In order to demonstrate the protective action of immune serum, therefore,
      it has been found necessary to employ a dosage of culture so small that if the
      bacteria are immediately killed, or their growth inhibited, no lesion results.
      Employing immune serum under these conditions, it has been found that the ability
      of the serum to prevent the occurrence of skin lesions has progressively
      increased with continuing immunization of the horse. A series of eighteen
      patients suffering from influenzal meningitis has been treated with Type b
      antiserum. Following the use of serum, recovery occurred in one patient of the
      series, and in two, although the patients ultimately died, the spinal fluid
      cultures became sterile and remained so for periods of 7 to 14 days. In four
      other cases, the spinal fluid cultures showed, temporarily, either no growth of
      bacteria, or a reduction of their number. Among five patients in whom septicemia
      was present before treatment, in four the blood cultures, after treatment with
      serum, became sterile. The number of patients treated has been small, and the
      treatments were carried out under widely varying conditions. It is difficult,
      therefore, to draw conclusions regarding the actual value of this form of
      therapy, or the best methods of procedure. The clinical results, however,
      indicate, as do the experimental, that the serum has a definite anti-infectious
      action. The experience is too limited to permit final conclusions regarding the
      importance of the addition of fresh (complement-containing) serum to the immune
      serum. Further experience, under more accurately controlled conditions, may show
      that the serum has greater practical value in treatment than is shown by the
      mortality results in this series of cases.

PMID- 19870225
TI  - CONCERNING THE RELATIVE RESPONSE TO BLOOD GAINS AND BLOOD LOSSES; AND HABITUATION
      TO AN EXCESS OF BLOOD PIGMENT.
AB  - The effects of very gradually increasing or diminishing the amount of circulating
      hemoglobin have been studied in rabbits. Contrary to expectation it was found
      that when the pigment was increased by the injection of a small quantity of
      compatible blood every day during some weeks the erythropoietic tissue did not
      lessen its activities. The hemoglobin percentage mounted gradually yet
      considerably when even as little as 1/100 of the amount of blood initially
      possessed by the animal was injected each day; and the figure it finally attained
      must in some instances at least have been expressive of a superabundance. To this
      superabundance the animal itself evidently contributed through its persisting
      erythropoietic activity. The results were very different when rabbits were bled
      daily to the same small amount that was injected into their fellows. The marrow
      became abnormally active, and this activity continued undiminished throughout the
      long period of the bleedings. The organism is evidently far more susceptible to
      blood losses than to blood gains, a fact which is scarcely surprising when one
      considers that throughout its differentiation as a going concern it has had to
      cope with exigencies of the first sort only. Rabbits in which the hemoglobin is
      very gradually increased by the injection of strange blood become so accustomed
      to the abundance of pigment that even a slight falling off causes the
      erythropoietic tissue to become abnormally active to maintain the new status quo.
      Good reasons exist for referring the habituation thus manifested to readjustments
      in the functioning of the physiological mechanisms which mediate between oxygen
      demand and erythropoietic response. Too little recognition has been given to the
      role of these mechanisms in such relation. No evidence was obtained of any
      effective readjustment to protect the erythropoietic tissue from the stimulus of
      daily small blood losses.

PMID- 19870226
TI  - CHEMOIMMUNOLOGICAL STUDIES ON THE SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS : I.
      THE ISOLATION AND PROPERTIES OF THE ACETYL POLYSACCHARIDE OF PNEUMOCOCCUS TYPE I.
AB  - The soluble specific substance of Pneumococcus Type I has been chemically
      isolated from the bacterial cells and from autolyzed cultures as an acetyl
      polysaccharide. So far as could be determined by the methods employed, the acetyl
      polysaccharide in highly purified form absorbs from Type I antipneumococcus serum
      all demonstrable type-specific precipitins, agglutinins and protective
      antibodies. Mice injected intraperitoneally with minute quantities of the acetyl
      polysaccharide develop active immunity to subsequent infection with Pneumococcus
      Type I. The immunity thus induced is type-specific. In several instances purpura
      has been observed in mice following the injection of larger amounts of the acetyl
      polysaccharide. Under the experimental conditions of this study, no type-specific
      precipitins, agglutinins or protective antibodies were demonstrable in the serum
      of rabbits following repeated intravenous injections of the Type I acetyl
      polysaccharide. The treated rabbits were not immune to subsequent infection with
      Pnemnococcus Type I. The acetyl polysaccharide is readily converted into its
      deacetylated derivative by treatment with dilute alkali. The chemical and
      immunological properties of the deacetylated polysaccharide are identical with
      those of the soluble specific substance in the chemical form in which it was
      originally isolated; the deacetylated form of the specific carbohydrate is non
      antigenic, does not produce purpura in mice, and only incompletely absorbs the
      type-specific antibodies from Type I antipneumococcus serum. The immunological
      significance of the acetyl polysaccharide and its possible relationship to the
      specific substances isolated from Pneumococcus Type I by other workers are
      discussed.

PMID- 19870227
TI  - AN INVESTIGATION OF THE ETIOLOGY OF MUMPS.
AB  - 1. From four out of six specimens of saliva from six cases of mumps in the early
      stages of the disease, a filterable cytotropic virus has been obtained which
      induces in M. rhesus monkeys, following inoculation of the parotid glands through
      Stensen's duct, an acute, non-suppurative parotitis analogous to mumps. 2. This
      virus has not been found in normal saliva, nor does it correspond to any known
      virus with which we are familiar. 3. The virus is free of demonstrable
      microorganisms including spirochetes. 4. It is judged that this virus is the
      causative agent of mumps.

PMID- 19870228
TI  - STUDIES ON THE NERVOUS SYSTEM IN DEFICIENCY DISEASES : II. LESIONS PRODUCED IN
      THE DOG BY DIETS LACKING THE WATER-SOLUBLE, HEAT-STABLE VITAMIN B(2)(G).
AB  - Adult dogs maintained on an artificial, balanced ration adequate in all dietary
      essentials as far as is known except water-soluble, heat-stable vitamin B(2) (G)
      developed, after a sufficient time, a slowly progressive disease characterized by
      loss of weight, persistent vomiting and diarrhea, and marked muscular weakness,
      which ended fatally in from 200 to over 300 days. The clinical features of this
      condition, as pointed out in the discussion, are quite different from those
      characterizing the canine disease known as black tongue. The anatomic changes in
      this condition consist of marked demyelination of the peripheral nerves,
      including the vagus; degeneration of the medullary sheaths and replacement by
      gliosis of the posterior columns of the spinal cord, particularly the fasciculi
      graciles; degeneration of the medullary sheaths of the posterior and less often
      of the anterior nerve roots of the cord; occasionally slight degenerative changes
      in most of the other fiber tracts of the cord. Attention is called to the fact
      that degenerative lesions in the central nervous system similar or identical with
      these have frequently been described in pellagra in man.

PMID- 19870229
TI  - NUTRITIONAL MYOPATHY IN DUCKLINGS.
AB  - Ducklings fed on a diet of skimmed milk powder, casein, corn-starch, lard, cod
      liver oil, yeast, salts and paper pulp rapidly develop a disease characterized by
      extreme and progressive myasthenia, ending in death within a few days.
      Pathological changes are found in the skeletal muscles. These show widespread
      hyaline necrosis of fibers, with edema and cellular reaction. The brain and other
      parts of the central nervous system are not affected, and no significant
      alterations are found in other viscera or tissues. The creatine content of the
      muscles is reduced in proportion to the muscle injury. Controls on a natural food
      diet remain free from the disease.

PMID- 19870230
TI  - AN INVESTIGATION INTO THE SIGNIFICANCE OF HORMONAL FACTORS IN EXPERIMENTAL
      POLIOMYELITIS.
AB  - 1. Adult rhesus monkeys possess frequently a greater resistance to experimental
      infection with poliomyelitis virus than young monkeys as indicated by the
      prolongation of the incubation period and the content of feeble neutralizing
      substances in the normal serum. 2. Virucidal substances can be demonstrated in
      the normal serum of subadult chimpanzees. 3. Immature monkeys prepared with
      glandular anterior pituitary hormones and anterior pituitary-like principles from
      the urine of pregnant women are protected only in exceptional instances against
      intracerebral infection with poliomyelitis virus. However, the serum of such
      prepared animals frequently acquires the property of inactivating the virus in
      vitro. 4. Active immunization with live poliomyelitis virus renders the immunized
      monkeys resistant to intracerebral infection in a higher percentage of the cases
      than does preparation with hormone. 5. The relative merits of non-specific
      enhancement of resistance and of specifically acquired immunity are discussed in
      their relation to the probable mechanism of resistance to poliomyelitis in man.

PMID- 19870231
TI  - A STUDY ON BACTERIAL PROTEINS WITH SPECIAL CONSIDERATION OF GONOCOCCUS AND
      MENINGOCOCCUS.
AB  - Methods of preparation and certain properties of the "nucleoproteins" of the
      following organisms are described: gonococcus, meningococcus, Micrococcus
      catarrhalis, R pneumococcus, Streptococcus hemolyticus, Staphylococcus aureus. No
      essential differences between the nucleoproteins and the intact cells of
      gonococcus and meningococcus were observed in their ability to engender immune
      substances (precipitins), to induce bacterial allergy in rabbits, or to elicit
      cutaneous reactions (of the delayed type) in rabbits rendered hypersensitive to
      these organisms. Measured by their lethal action in mice, the toxicity of
      gonococcal and meningococcal nucleoproteins was found to be but slightly less
      than that of the intact cells. It seems probable, therefore, that the toxic
      action of these organisms is due, chiefly or entirely, to some constituent of the
      nucleoprotein fraction. Extraction with acetone and ether in the cold did not
      reduce appreciably the toxicity of these organisms and their nucleoproteins, nor
      alter their immunological behavior. Cross-precipitin reactions suggested that
      gonococcal nucleoprotein contains an antigenic factor in common with the non
      encapsulated pneumococcus cell, and meningococcal nucleoprotein one in common
      with the capsular material of Pneumococcus Type III. Tryptic digestion destroys
      these antigenic factors, but not those responsible for the cross-reactions within
      the genus Neisseria.

PMID- 19870232
TI  - THE CARBOHYDRATES OF GONOCOCCUS AND MENINGOCOCCUS : I. THE ALCOHOL-PRECIPITABLE
      FRACTION.
AB  - The alcohol-insoluble polysaccharides of gonococcus and meningococcus were found
      to contain 4.2 and 3.7 per cent nitrogen respectively, to be protein-free by
      chemical test, to reduce FehIing-Benedict solution only after hydrolysis. They
      were non-toxic for rabbits and mice, and failed to engender antibodies
      (precipitins) in rabbits. They produced no cutaneous reactions in normal, snuffle
      free rabbits, but caused typical allergic reactions of the delayed type in
      rabbits rendered hypersensitive to these organisms. Both carbohydrates reacted in
      high dilution with Antipneumococcus Serum Type III. For comparison, carbohydrates
      were prepared also from Micrococcus catarrhalis, Streptococcus hemolyticus,
      Staphylococcus aureus, and a rough strain of pneumococcus.

PMID- 19870233
TI  - THE TOXIC PROPERTIES OF SERUM EXTRACTS OF HEMOLYTIC STREPTOCOCCI.
AB  - 1. A method is described whereby toxic substances may be extracted from hemolytic
      streptococci with inactivated serum. 2. Such extracts contain large amounts of
      hemotoxin and leucocidin. 3. Their intravenous injection into mice causes marked
      hemoglobinuria, anemia, and death. 4. There is evidence that this anemia is not
      the only cause of death of these animals. 5. Incomplete work seems to indicate
      that the hemotoxin and the lethal poisons are not antigenic. 6. Certain
      biological properties of the extract are described.

PMID- 19870234
TI  - FURTHER OBSERVATIONS ON PATHOLOGIC SIMILARITIES BETWEEN EXPERIMENTAL SCURVY
      COMBINED WITH INFECTION, AND RHEUMATIC FEVER.
AB  - In the guinea pig, chronic scurvy with superimposed infection (beta
      streptococcus) and to a lesser extent chronic scurvy alone, produces an
      arthropathy with striking pathologic similarities to that of rheumatic fever and
      the closely allied condition of rheumatoid arthritis. Considerable significance
      is attached to the widespread occurrence in the experimental animal subjected to
      scurvy and infection, and to a lesser extent in scurvy alone, of lesions similar
      to if not identical with the fibrinoid degeneration which has been considered the
      fundamental lesion of rheumatic fever. A subcutaneous nodule essentially similar
      to the subcutaneous nodules of rheumatic fever was observed in one experimental
      animal. Attention is called to a group of general pathologic changes frequently
      observed in rheumatic fever which were also found in the experimental animals
      subjected to scurvy and infection. These include degenerative changes in skeletal
      muscle, focal necrosis in the liver, fibrosis of the Malpighian bodies in the
      spleen, erythrophagocytosis in the lymph nodes, and focal lymphocytic
      accumulations in the kidneys. The problem of hemorrhage is considered. It is
      suggested that a scorbutic state may be the basis of the hemorrhagic
      manifestations common to the acute phases of rheumatic fever. The unsatisfactory
      nature of previous experimental attempts to reproduce the pathology of rheumatic
      fever is noted. The lesions produced by subjecting the guinea pig to the combined
      influence of scurvy and infection are considered to be fundamentally similar in
      character and distribution to those of rheumatic fever. The pathologic
      observations recorded in this and a previous publication (2) are believed to
      offer evidence that the disease known as rheumatic fever may be the result of the
      combined influence of scurvy and infection. It is suggested that a subclinical
      degree of scurvy may constitute the rheumatic tendency in which the added factor
      of infection causes the development of rheumatic fever or possibly the closely
      allied condition of rheumatoid arthritis. Epidemiological and clinical
      considerations appear to afford supportive evidence to this concept.

PMID- 19870235
TI  - ACUTE ASCENDING MYELITIS FOLLOWING A MONKEY BITE, WITH THE ISOLATION OF A VIRUS
      CAPABLE OF REPRODUCING THE DISEASE.
AB  - A case of acute ascending myelitis which followed the bite of an apparently
      normal Macacus rhesus monkey is described. The clinical course as well as the
      pathological changes has been studied and found to be suggestive of a virus cause
      for the disease. The absence of perivascular demyelinization removes the case
      from the realm of acute disseminated encephalomyelitis and establishes it more or
      less definitely as a primary acute infectious myelitis. An extremely important
      feature of the pathological picture of this disease has been the presence of
      focal necrosis in the viscera (spleen, adrenals, regional lymph nodes). Attempts
      to transmit the disease to Macacus rhesus monkeys, dogs, mice, and guinea pigs,
      employing glycerinated organs from the human case, proved unsuccessful. By the
      inoculations of rabbits the presence of a strongly neurotropic, filtrable virus
      was demonstrated in the patient's brain, cord, and spleen. Following
      intracutaneous injection of it as derived either from brain and cord or spleen,
      an experimental disease develops in rabbits which strikingly resembles the human
      disease in the character of the local lesion, the incubation period, development
      of urinary retention, and flaccid paralysis of the posterior extremities with
      cephalad progression, death by respiratory failure, and finally by the occurrence
      of focal necrosis in the spleen, adrenals, and liver. In attempting to establish
      the identity of this virus, (the B virus), a consideration of its biological
      properties excludes the viruses of poliomyelitis, rabies, vaccinia, Virus III
      disease of rabbits, and the other viruses which are known to produce similar
      intranuclear inclusion bodies, except perhaps herpes. Although the relationship
      between the B virus and the virus of herpes must still be determined by cross
      immunity tests it has been shown to possess certain properties which warrant
      consideration of it as a distinct entity.

PMID- 19870236
TI  - EXPERIMENTS ON THE CONVERSION OF TYPHUS STRAINS.
AB  - TWO TYPES OF STRAINS OF TYPHUS VIRUS ARE OBSERVED IN MEXICO: first the murine
      type which is obtained from wild rats in nature, from isolated endemic cases, and
      from cases during short epidemic outbreaks, and second, the epidemic type of
      strains which is obtained from long standing serious epidemics. Some of these
      epidemic strains correspond entirely to strains of historic Old World typhus.
      Other strains which in their experimental behavior are intermediate between these
      two types of strains were isolated from the same epidemic. A method is described
      by which these epidemic non-orchitic strains can be converted into murine strains
      regularly causing scrotal lesion in guinea pigs and a highly fatal disease in
      rats. The same results were obtained with an Old World strain of epidemic typhus.
      The method, which consists of daily blood injections into intraperitoneally
      inoculated rats, is based on the observation that Rickettsia prowazeki multiplies
      only within cells which come in constant or frequent contact with fresh blood. It
      is concluded from our experiments that there does not exist any real difference
      between the virus of historic Old World typhus and the murine New World typhus.
      Both are considered to be of murine origin. The murine strains represent the
      original form of the virus of typhus, whereas the epidemic strains are the result
      of a prolonged propagation in the cycle man-louse-man.

PMID- 19870237
TI  - COMPARATIVE STUDIES ON THE VIRUSES OF VESICULAR STOMATITIS AND EQUINE
      ENCEPHALOMYELITIS (1).
AB  - We have studied certain properties, additional to those previously described (3),
      of the virus of vesicular stomatitis of horses, and of the characteristic
      biological reactions of the virus of equine encephalomyelitis. It has been found
      that the virus of stomatitis, ordinarily dermotropic, can acquire neurotropism
      and the neurotropic encephalomyelitis virus can, in turn, be rendered dermotropic
      in its action. The neurotropism in both instances is associated with definite,
      although not pronounced, viscerotropism. Both viruses can bring about a similar
      infection in the white mouse, rat, guinea pig, rabbit, and rhesus or cynomolgus
      monkeys. Of these animals, rabbits show the lowest degree of susceptibility and
      mice the highest, especially after intracerebral inoculation. The mouse is the
      best animal for work with these viruses because of the uniform and rapidly lethal
      encephalitis which can be induced in it. Moreover, the mouse is highly sensitive
      to the instillation of the viruses in the nasal passages: 1 to 10 million
      dilution sufficing to induce a fatal encephalitis. The uninjured nasal mucosa of
      mice appears, therefore, to be as susceptible to experimental infection as the
      traumatized brain or pads of animals. The microscopic changes accompanying the
      reactions to both viruses reveal, in rapidly lethal infections, pronounced
      destructive lesions in the cells of the central nervous system. When the
      experimental disease is more protracted in its course, however, these lesions are
      associated with beginning productive, inflammatory reactions, consisting chiefly
      of mononuclear infiltrations. In the latter instances, characteristic,
      intranuclear inclusion bodies can be more readily observed. Both viruses can be
      cultivated with facility in the medium of minced chicken embryonic tissue
      suspended in Tyrode's solution, although 24 to 48 hour old chicks are refractory
      to artificial infection. No cross-immunity reactions occur between the two
      strains of stomatitis virus or between them and the encephalomyelitis strain. The
      viruses are evidently similar in many biological properties. In view of the fact
      that the horse is the natural host for both, it is suggested that they may be
      generically related. They are not, of course, identical since cross-immunity
      between them does not exist. The absence of cross-immunity does not, however,
      exclude the possibility of a generic relationship, for there are at least three
      immunologically distinct types of foot-and-mouth disease, two of vesicular
      stomatitis, and two of equine encephalomyelitis (14) virus.

PMID- 19870238
TI  - THE PULMONARY ARTERIAL PRESSURE IN NORMAL ALBINO RATS AND THE EFFECT THEREON OF
      EPINEPHRINE.
AB  - 1. A satisfactory method for the direct determination of the pulmonary arterial
      pressure in rats is described. 2. The arithmetical mean of the blood pressure in
      the pulmonary artery in a series of thirty-four normal albino rats under nembutal
      anesthesia is 256 mm. H(2)0 (18.8 mm. Hg). 3. Intravenous epinephrine causes an
      abrupt but briefly sustained rise in the pulmonary arterial pressure with a
      gradual return to normal.

PMID- 19870239
TI  - PULMONARY HYPERTENSION IN RATS LIVING UNDER COMPRESSED AIR CONDITIONS.
AB  - 1. Pulmonary arterial hypertension was demonstrated in a series of rats that had
      been kept for 24-31 days in an environment of compressed air, having a barometric
      pressure of 3040 mm. Hg. The partial pressure of oxygen was 635 mm. Hg, which is
      equivalent to an 83.6 per cent oxygen mixture at normal barometric pressure. 2.
      Sclerosing changes in the pulmonary arterioles have been observed which precede
      the development of demonstrable hypertension in the pulmonary circulation. These
      vessels showed histological changes that were indicative of injury after 3 days
      of exposure. There was a thickening of the walls which stained more intensely
      with eosin, as well as marked perivascular edema and often a narrowing of the
      lumina. Progressive thickening, narrowing, and hyalinization of the pulmonary
      arterioles occurred later, after the disappearance of perivascular edema. These
      changes appeared very similar to the renal arterial lesions seen at autopsy in
      patients dying from malignant hypertension. 3. Pathological examination did not
      reveal significant or constant changes from normal in any organs except the lungs
      and heart. The blood vessels of the systemic circulation showed no pathological
      change. 4. The walls of the large pulmonary arteries increased in thickness
      rapidly after the 3rd day of exposure. This change was due to the progressive
      formation and condensation of fibrous tissue outside of the media and to a lesser
      extent to thickening of the alternate layers of elastic tissue and smooth muscle
      in the arterial wall. 5. Marked dilatation of the right ventricle and conus
      arteriosus as well as small areas of scar tissue formation in the right ventricle
      were present on prolonged exposure. A few hearts showed larger areas of fibrosis
      that were visible on macroscopic examination. 6. The systemic arterial blood
      pressure of a small series of rats exposed to compressed air for 38 days and
      examined 7 to 10 days after decompression was in each instance less than one-half
      the average normal pressure. 7. The findings in this study are consistent with
      the clinical and pathological signs of pulmonary hypertension in man. 8. The
      anatomical alterations observed in the alveolar units of the lungs were
      essentially the same as those previously described (1). 9. A method has been
      devised whereby pulmonary arterial hypertension, accompanied by important
      sclerotic changes in the arteries of the pulmonary circulation can be induced for
      investigation.

PMID- 19870240
TI  - ENERGY METABOLISM OF THE FAILING HEART.
AB  - The failing heart is found to liberate energy in contraction to the same extent
      at any fiber length as the normal heart muscle, but it is unable to convert as
      much of the energy into useful work. Its efficiency as a machine is impaired. In
      the light of these observations the word "tonus" as applied to heart muscle
      becomes synonymous with "efficiency." The implications of these findings in
      applied cardiology are discussed.

PMID- 19870241
TI  - SWINE INFLUENZA : V. STUDIES ON CONTAGION.
AB  - A strain of swine influenza has been observed to change from a condition of full
      contagiousness, in which both H. influenzae suis and the swine influenza virus
      were transferred by pen contact, to one of only partial contagiousness, in which
      the virus alone was transferred, resulting in the mild filtrate disease instead
      of swine influenza in animals infected by contact. Swine that had been
      experimentally converted into carriers of H. influenzae suis developed swine
      influenza following contact with animals infected with the altered strain of the
      disease. Experiments in which the etiological components of a freshly obtained
      and fully contagious strain of swine influenza were substituted for the
      corresponding components of the altered strain of the disease revealed the fact
      that the change in the contagious character of the latter was due to an
      alteration in the bacterial component of the etiological complex and that the
      virus component was in no way responsible.

PMID- 19870242
TI  - ON SPECIFIC INHIBITION OF BACTERIOPHAGE ACTION BY BACTERIAL EXTRACTS.
AB  - 1. Experiments are presented demonstrating specific inhibition of phage by
      soluble products of bacteria. 2. The inhibition proceeds more rapidly when the
      phage and bacterial extracts are incubated at 37 degrees than at ice box
      temperature. 3. The specificity of the reaction in the instances studied is
      probably connected with the presence of specific soluble carbohydrates. 4. A
      reaction is available for the study of the chemistry of bacillary antigens in
      terms of bacteriophage.

PMID- 19870243
TI  - THE RELATION OF COAT COLOR TO THE SPONTANEOUS INCIDENCE OF MAMMARY TUMORS IN
      MICE.
AB  - 1. The material included in this paper consists of F(1) and F(2) virgin female
      mice derived from a cross between a strain high in mammary cancer incidence
      (dilute brown) and one relatively low in incidence of mammary cancer but
      relatively high in the incidence of various internal tumors (yellow). 2. In the
      F(1) and F(2) hybrid generations the yellow animals have a significantly lower
      incidence of mammary tumors than do the non-yellows. This is the first clear case
      of a difference in the incidence of spontaneous tumors in mice associated with a
      color difference. 3. Mammary tumors occur, however, significantly earlier in the
      yellow mice and are just as malignant as those appearing in the non-yellows. 4.
      The incidence of tumors other than mammary is not significantly different in the
      yellow and non-yellow hybrids. Such tumors, however, occur distinctly later in
      life than do the mammary tumors. This provides additional evidence that, in mice,
      mammary tumors cannot be considered to be the same biological phenomenon as are
      other types of tumor. 5. A study of the physiology of reproduction of yellow and
      non-yellow mice within the yellow stock suggests that the yellows pass through
      their reproductive cycle earlier than do the non-yellows. The duration of the
      cycle in the two forms is essentially equal. This fact would satisfactorily
      explain the earlier incidence of mammary tumors in yellow mice. 6. The lower
      incidence of mammary tumors in yellows as compared with non-yellows may be at
      least in part due to the same phenomenon. This would follow because the
      opportunity for mammary tissue in yellow mice of cancer age to be continuously
      affected by ovarian secretion would be less than in non-yellows. This would
      result in a higher percentage of yellows reaching an age at which stimuli from
      the ovary ceased before the mammary tissue had reached an age at which tumor
      formation is most frequent. 7. There is some evidence that, in this cross, dilute
      (d(b)d(b)) mice are less apt to form mammary tumors than are intensely pigmented
      animals. This point, however, needs further investigation before it can be
      considered to be established. 8. The facts recorded in this paper demonstrate
      that not all forms of tumor or all colors of mice can be lumped together in
      studying either the physiology or genetics of spontaneous tumor incidence.

PMID- 19870244
TI  - BLOOD PLASMA PROTEIN REGENERATION CONTROLLED BY DIET : I. LIVER AND CASEIN AS
      POTENT DIET FACTORS.
AB  - When blood plasma proteins are depleted by bleeding and return of the washed red
      cells (plasmapheresis) the regeneration of new plasma proteins can be controlled
      at will by diet. The amount and character of protein intake is all important.
      Liver protein and casein are efficient proteins to promote rapid regeneration of
      plasma proteins but some vegetable proteins are also efficient. The blood plasma
      proteins are reduced by plasmapheresis close to the edema level (3.5-4.0 per
      cent) and kept at this level by suitable exchanges almost daily. The amount of
      plasma protein removed is credited to the given diet period. A basal ration is
      used which is poor in vegetable protein (potato) and contains no animal protein.
      The dog on this ration can be kept in nitrogen balance but can produce only about
      2 gm. plasma protein per kilo body weight per week. With liver or casein feeding
      this production can be increased three- or fourfold. A reserve of protein
      building material can be demonstrated in the normal dog when its plasma proteins
      are depleted. In the first 3 weeks of depletion this reserve in excess of the
      final basal output may amount to 3-20 gm. protein. This may be stored at least in
      part in the liver. As much as 50 per cent of this reserve may be albumin or
      albumin producing material. A reversal of the albumin-globulin ratio may be
      observed on the basal diet alone. The reversal will always follow plasmapheresis
      with the dog on the basal diet and the total plasma protein output will consist
      approximately of 2 parts globulin and 1 part albumin. Liver diet will raise the
      production and output of albumin and bring the ratio back toward normal. Albumin
      production may actually exceed the globulin output during liver diet periods. The
      change is less conspicuous with casein but in the same direction.

PMID- 19870245
TI  - BLOOD PLASMA PROTEIN GIVEN BY VEIN UTILIZED IN BODY METABOLISM : II. A DYNAMIC
      EQUILIBRIUM BETWEEN PLASMA AND TISSUE PROTEINS.
AB  - Large amounts of normal blood plasma can be given intravenously to normal dogs
      over several weeks without causing any significant escape by way of the urine.
      There appears to be no renal threshold for plasma protein even with high plasma
      protein concentration (9.7 per cent). Dogs receiving sugar by mouth and plasma by
      vein can be kept practically in nitrogen equilibrium and it would seem that the
      injected protein must be utilized by the body. If this can happen in this
      emergency we may suspect that normally there is a certain amount of "give and
      take" between body protein and plasma protein. Plasma protein fed by mouth under
      identical conditions shows the same general reaction as noted with plasma by vein
      but the urinary nitrogen is a little higher and suggests that the injected
      protein is utilized a little more completely to form new protein. The difference
      may be explained as due to deaminization in the case of protein by mouth. During
      fasting periods the blood plasma proteins are used up and the total circulating
      protein may even decrease to one-half the normal level. The plasma protein
      concentration changes but little and the significant change is a shrinkage of
      plasma volume. All these facts point to a dynamic equilibrium between tissue
      protein and plasma protein depending upon the physiological needs of the moment.
      In the absence of food protein the body can use material coming from one body
      protein to fabricate badly needed protein material of different character.

PMID- 19870246
TI  - PERIVASCULAR REACTIONS IN LUNG AND LIVER FOLLOWING INTRAVENOUS INJECTION OF
      STREPTOCOCCI INTO PREVIOUSLY SENSITIZED ANIMALS.
AB  - Intravenous inoculation of small doses of non-hemolytic streptococci into
      previously sensitized rabbits is usually followed by the appearance of
      perivascular cellular aggregates in lung and liver. The characteristic cell in
      these aggregates is moderately large, with vesicular nucleus, prominent nucleoli,
      clumped chromatin, and basophilic cytoplasm. In addition, the lesions contain
      small lymphocytes and granulocytes. This lesion is easily differentiated by
      architecture and cell content from normally occurring lymphoid aggregates, and
      from spontaneous rabbit hepatic cirrhosis. This mononuclear response does not
      occur when the intravenous dose is large enough to cause death of the animal
      within 24 hours. In spleen and lymph nodes the characteristic basophilic cells,
      which normally occur in these organs, are present in increased numbers. Following
      intravenous treatment alone, or sensitization without intravenous treatment, the
      lesions occur much less frequently, and when present are smaller and more
      sparsely found. Inasmuch as in the present series of experiments this lesion was
      not found in normal animals, and infrequently in those treated by the intravenous
      route alone, it is suggested that the preliminary sensitization serves to enhance
      the animal's reactivity to the antigen. In this way a small dose of bacteria is
      capable of eliciting the cellular phenomenon, which in unsensitized animals
      appears only when larger doses of antigen are administered over longer periods of
      time. Too large a dose of antigen, however, results in shock and cell death
      rather than proliferation.

PMID- 19870247
TI  - SINGLE CELL INOCULATIONS WITH TREPONEMA PALLIDUM.
AB  - The injection of one or several Treponema pallidum into the testicles of rabbits
      does not induce syphilitic infection. A negative tissue transfer experiment does
      not preclude the presence of Treponema pallidum in the inoculum nor does it
      indicate the absence of syphilis in the source animal.

PMID- 19870248
TI  - RIFT VALLEY FEVER IN MAN : REPORT OF A FATAL LABORATORY INFECTION COMPLICATED BY
      THROMBOPHLEBITIS.
AB  - A case of Rift Valley fever following an accidental laboratory infection, and
      believed to be the first instance of the disease in the Western hemisphere, is
      reported. Although the course of illness was otherwise quite typical, it was
      complicated by thrombophlebitis-a condition not previously described in
      association with this disease in man. Death was caused by a pulmonary embolus.

PMID- 19870249
TI  - THE VITAMIN B(1) AND B(2) G CONTENT OF LIVER EXTRACT AND BREWERS' YEAST
      CONCENTRATE.
AB  - 1. Liver extract powder, No. 343 Lilly, and the same material prepared for
      parenteral use, when administered daily by mouth in amounts derived from 2.5 gm.
      of fresh whole liver, to rats weighing from 40 to 50 gm., contain sufficient
      vitamin B(1) to support normal growth, provided the animals receive in addition
      an adequate amount of vitamin B(2) G. Moreover, liver extract in the forms
      mentioned, administered in the same amounts, does not contain sufficient vitamin
      B(2) G to maintain normal growth of similar rate when all other necessary
      constituents of the diet are provided. 2. Liver extract (Lilly) in the form
      prepared for parenteral use, when administered daily by intraperitoneal
      injections, in amounts derived from 2.5 gm. of fresh whole liver, to rats under
      standard experimental conditions, does not contain sufficient vitamin B(2) G to
      maintain normal growth. Furthermore, the amount of vitamin B(1) present in liver
      extract in this form is not as effective in supporting normal growth when given
      by intraperitoneal injection as it is when given by mouth. 3. Vegex, when
      administered daily in amounts of 50, 150, and 250 mg. to rats of 40 to 50 gm. in
      weight contains sufficient vitamin B(1) to maintain normal growth of the rats,
      provided the animals receive in addition an adequate amount of vitamin B(2) G.
      However, vegex in the same amounts does not contain sufficient vitamin B(2) G to
      support normal growth of similar rats when all other necessary constituents of
      the diet are provided. 4. These experiments indicate that the extrinsic, anti
      anemic factor of Castle and the thermostable growth-promoting food constituent,
      commonly known as vitamin B(2) G, are not identical.

PMID- 19870250
TI  - THE EFFECT OF HEMOGLOBIN INJECTIONS ON ERYTHROPOIESIS AND ERYTHROCYTE SIZE IN
      RABBITS RENDERED ANEMIC BY BLEEDING.
AB  - 1. An anemia characterized by increased size of the red blood cells and a high
      color index was produced in rabbits by repeated bleeding and by the subcutaneous
      injection of stroma-free hemoglobin solution. 2. The bone marrow of these rabbits
      reverted to a more primitive stage than did the marrows of rabbits rendered
      anemic in the same manner but not treated with hemoglobin.

PMID- 19870251
TI  - STUDIES ON EXPERIMENTAL HYPERTENSION : I. THE PRODUCTION OF PERSISTENT ELEVATION
      OF SYSTOLIC BLOOD PRESSURE BY MEANS OF RENAL ISCHEMIA.
AB  - These experiments indicate that, in dogs at least, ischemia localized to the
      kidneys is a sufficient condition for the production of persistently elevated
      systolic blood pressure. When the constriction of both main renal arteries is
      made only moderately severe in the beginning, the elevation of systolic blood
      pressure is unaccompanied by signs of materially decreased renal function. In
      this respect the hypertension in these animals resembles the hypertension which
      is associated with so called benign nephrosclerosis in man. Subsequent increase
      of the constriction of the main renal arteries does not materially damage renal
      function, probably because of adequate development of accessory circulation. More
      delicate methods for detecting a change may yet prove that some damage does
      occur. Almost complete constriction of both main renal arteries, from the
      beginning, results in great elevation of systolic blood pressure which is
      accompanied by severe disturbance of renal function and uremia. This resembles
      the type of hypertension which is associated with so called malignant
      nephrosclerosis, in the sense of Fahr (17). In several of the animals with
      persistent elevation of systolic blood pressure, anatomical changes were observed
      in the glomeruli, vessels and parenchyma of the kidneys which are most probably
      directly referable to the ischemia. It is hoped that these investigations will
      afford a means of studying the pathogenesis of hypertension that is associated
      with renal vascular disease.

PMID- 19870252
TI  - BACTERIAL GROWTH AND MULTIPLICATION AS DISCLOSED BY MICRO MOTION PICTURES.
AB  - Using a micro motion picture technique for making records, studies covering
      several thousand hours of observation have been made of the growth of a number of
      bacteria. On the basis of these experiments a discussion is offered of bacterial
      division and its influence on gross colony appearance, of different kinds of
      pleomorphism that have been observed, and of the nature of the internal structure
      that is seen in some bacteria. Several of the microorganisms chosen for
      examination are ones that have been thought to give evidence of life cycle
      phenomena. The present pictures, however, contain no evidence of a bacterial
      cycle in the commonly accepted meaning of the term.

PMID- 19870253
TI  - THE FILTERING CAPACITY OF LYMPH NODES.
AB  - In anesthetized dogs the popliteal lymph node alone, and the popliteal and iliac
      lymph nodes in series, have been perfused with solutions containing dog
      erythrocytes and streptococci. The perfusions have been carried out under
      conditions of lymph flow and pressure within the limits of those occurring in the
      actively moving dog, or after a severe degree of inflammatory swelling has
      developed. Figures for filtration are given, with protocols of typical
      experiments. They indicate that normal lymph nodes possess a high degree of
      filtering efficiency-an efficiency so great as to make it fairly certain that in
      a part kept at rest early in an infection, practically no microorganisms would
      escape the nodes in the line of drainage.

PMID- 19870254
TI  - I. CHOLESTEROL AND CHOLESTEROL ESTERS IN DOG BILE : QUANTITATIVE METHODS.
AB  - The colorimetric method for the determination of total cholesterol in dog bile is
      consistently accurate as checked by the oxidative digitonin method. This method
      has the further advantages of being simple, rapid and economical. A method for
      the determination of esterified cholesterol in bile is described and it is shown
      that there are no esters of cholesterol in normal dog bile.

PMID- 19870255
TI  - II. BILE CHOLESTEROL : FLUCTUATIONS DUE TO DIET FACTORS, BILE SALT, LIVER INJURY
      AND HEMOLYSIS.
AB  - Under uniform diet conditions the normal bile fistula dog will eliminate pretty
      constant amounts of cholesterol-about 0.5 to 1.0 mg. cholesterol per kilo per 24
      hours. Diets rich in cholesterol (egg yolk) will raise the cholesterol output in
      the bile but compared to the diet intake (1.5 gm. cholesterol) the output
      increase in the bile is trivial (5-15 mg.). Calves' brains in the diet are inert.
      Bile salt alone will raise the cholesterol output in the bile as much and often
      more than a cholesterol rich diet. Bile salt plus egg yolk plus whole bile give
      maximal output figures for bile cholesterol-60 mg. per 24 hours. Liver injury
      (chloroform) decreases both bile salt and cholesterol elimination in the bile.
      Blood destruction (hydrazine) fails to increase the bile cholesterol output and
      this eliminates the red cell stroma as an important contributing factor. Certain
      cholagogues (isatin and decholin) will increase the bile flow but cause no change
      in cholesterol elimination. The ratio of cholesterol to bile salt in the bile
      normally is about 1 to 100 but the bile salts are more labile in their
      fluctuations. The ratio is about reversed in the circulating blood plasma where
      the cholesterol is high (150-300 mg. per cent) and the bile salt concentration
      very low. Cholesterol runs so closely parallel to bile salt in the bile that one
      may feel confident of a physical relationship. In addition there is a suspicion
      that the bile cholesterol is in some obscure fashion linked with the
      physiological activity of hepatic epithelium.

PMID- 19870256
TI  - III. BLOOD PLASMA CHOLESTEROL : FLUCTUATIONS DUE TO LIVER INJURY AND BILE DUCT
      OBSTRUCTION.
AB  - Hypocholesteremia with dissociation of the normal ratio of esterified to total
      cholesterol is related to chronic liver injury caused by chloroform.
      Hypercholesteremia may develop after prolonged biliary obstruction. The
      hypercholesteremia of chronic biliary obstruction may be promptly reduced below
      normal by chloroform poisoning or bile duct infection. Acute injury of liver due
      to chloroform anesthesia may cause no change in blood plasma cholesterol. Absence
      of bile in the intestine with faulty fat absorption does not cause the
      development of hypocholesteremia with dissociation of the ester ratio. Poor food
      consumption or short periods of fasting may cause no change in blood plasma
      cholesterol. Liver cells injured by chloroform may subsequently become resistant
      to chloroform. After prolonged biliary obstruction, the liver is apparently more
      sensitive to small doses of chloroform by mouth. Analysis of blood plasma
      cholesterol may have a clinical application in differentiation between simple
      obstructive and parenchymatous lesions of the liver.

PMID- 19870257
TI  - A SEROLOGICAL DIFFERENTIATION OF SPECIFIC TYPES OF BOVINE HEMOLYTIC STREPTOCOCCI
      (GROUP B).
AB  - Under uniform diet conditions the normal bile fistula dog will eliminate pretty
      constant amounts of cholesterol-about 0.5 to 1.0 mg. cholesterol per kilo per 24
      hours. Diets rich in cholesterol (egg yolk) will raise the cholesterol output in
      the bile but compared to the diet intake (1.5 gm. cholesterol) the output
      increase in the bile is trivial (5-15 mg.). Calves' brains in the diet are inert.
      Bile salt alone will raise the cholesterol output in the bile as much and often
      more than a cholesterol rich diet. Bile salt plus egg yolk plus whole bile give
      maximal output figures for bile cholesterol-60 mg. per 24 hours. Liver injury
      (chloroform) decreases both bile salt and cholesterol elimination in the bile.
      Blood destruction (hydrazine) fails to increase the bile cholesterol output and
      this eliminates the red cell stroma as an important contributing factor. Certain
      cholagogues (isatin and decholin) will increase the bile flow but cause no change
      in cholesterol elimination. The ratio of cholesterol to bile salt in the bile
      normally is about 1 to 100 but the bile salts are more labile in their
      fluctuations. The ratio is about reversed in the circulating blood plasma where
      the cholesterol is high (150-300 mg. per cent) and the bile salt concentration
      very low. Cholesterol runs so closely parallel to bile salt in the bile that one
      may feel confident of a physical relationship. In addition there is a suspicion
      that the bile cholesterol is in some obscure fashion linked with the
      physiological activity of hepatic epithelium.

PMID- 19870258
TI  - LOSS OF THE PROPERTIES OF HEMOLYSIN AND PIGMENT FORMATION WITHOUT CHANGE IN
      IMMUNOLOGICAL SPECIFICITY IN A STRAIN OF STREPTOCOCCUS HAEMOLYTICUS.
AB  - 1. A variant arising in a culture of hemolytic streptococcus was shown to have
      lost the properties of producing pigment and hemolyzing blood. Despite the loss
      of these two functions, it had in common with the strain from which it was
      derived certain other distinguishing biochemical characteristics, as follows:
      Both attained the same hydrogen ion concentration in dextrose broth; both
      hydrolyzed sodium hippurate, grew on bile agar, and fermented trehalose but not
      sorbitol; both failed to reduce methylene blue in milk cultures, and were
      insusceptible to the action of streptococcus bacteriophage. In addition, the
      virulence of the variant remained the same as that of the original culture. 2.
      The antigenic and serological specificity of the variant was identical with the
      group and type specificity of the original strain (Group B, Type I). These
      specificities were established by the use of immune sera prepared by immunization
      of rabbits with each form. The immunological reactions employed were reciprocal
      agglutination, precipitation, agglutinin and precipitin absorption, and passive
      mouse protection.

PMID- 19870259
TI  - STUDIES ON TYPHUS FEVER : XII. THE PASSIVE IMMUNIZATION OF GUINEA PIGS, INFECTED
      WITH EUROPEAN VIRUS, WITH SERUM OF A HORSE TREATED WITH KILLED RICKETTSIA OF THE
      MEXICAN TYPE.
AB  - Under uniform diet conditions the normal bile fistula dog will eliminate pretty
      constant amounts of cholesterol-about 0.5 to 1.0 mg. cholesterol per kilo per 24
      hours. Diets rich in cholesterol (egg yolk) will raise the cholesterol output in
      the bile but compared to the diet intake (1.5 gm. cholesterol) the output
      increase in the bile is trivial (5-15 mg.). Calves' brains in the diet are inert.
      Bile salt alone will raise the cholesterol output in the bile as much and often
      more than a cholesterol rich diet. Bile salt plus egg yolk plus whole bile give
      maximal output figures for bile cholesterol-60 mg. per 24 hours. Liver injury
      (chloroform) decreases both bile salt and cholesterol elimination in the bile.
      Blood destruction (hydrazine) fails to increase the bile cholesterol output and
      this eliminates the red cell stroma as an important contributing factor. Certain
      cholagogues (isatin and decholin) will increase the bile flow but cause no change
      in cholesterol elimination. The ratio of cholesterol to bile salt in the bile
      normally is about 1 to 100 but the bile salts are more labile in their
      fluctuations. The ratio is about reversed in the circulating blood plasma where
      the cholesterol is high (150-300 mg. per cent) and the bile salt concentration
      very low. Cholesterol runs so closely parallel to bile salt in the bile that one
      may feel confident of a physical relationship. In addition there is a suspicion
      that the bile cholesterol is in some obscure fashion linked with the
      physiological activity of hepatic epithelium.

PMID- 19870260
TI  - ON THE USE OF ADSORBENTS IN IMMUNIZATIONS WITH HAPTENS.
AB  - Experiments are described which confirm the observation of Gonzalez and Armangue
      that heterogenetic extracts can be made antigenic by adsorption to inorganic
      materials. With fractions of the original extracts from which a part of inactive
      material had been removed no such enhancement was observed, whereas with foreign
      protein an activation was still possible. Carbohydrate preparations behaved
      similarly in that purification, perhaps loss of protein, was accompanied by a
      distinct decrease in antigenicity after adsorption. The activity of a but
      slightly antigenic heteroalbumose preparation was markedly increased after
      adsorption to charcoal and alum. The most reasonable explanation for the effects
      observed by Gonzalez and Armangue, and Zozaya, seems to be that a preexisting
      antigenic capacity has been enhanced by the use of adsorbents. The experiments
      reported here support the view that these effects are influenced significantly by
      the presence of substances other than those of a specific nature.

PMID- 19870261
TI  - VIABLE LEISHMANIA DONOVANI IN NASAL AND ORAL SECRETIONS OF PATIENTS WITH KALA
      AZAR AND THE BEARING OF THIS FINDING ON THE TRANSMISSION OF THE DISEASE.
AB  - 1. Smears from the nasal cavities of fifteen patients suffering from kala-azar
      have been examined and in nine of these typical Leishman-Donovan bodies have been
      found. 2. Smears from the surface of the tonsil and from the saliva in one of the
      above nine cases showed the presence of leishmania. The tonsils of this patient,
      who died as the result of kala-azar and secondary infection, at autopsy were
      shown to be massively infected with Leishman-Donovan bodies. 3. Leishmania in the
      nasal discharge of two patients were shown by inoculation into susceptible
      animals to be viable and capable of producing infection. Sufficient time has not
      elapsed to determine the viability of the organisms from the remaining cases. 4.
      These experiments show for the first time that a rich source of infective
      material from a large proportion of patients with kala-azar is available for
      direct transmission of the disease. 5. Strong evidence is presented as a basis
      for the concept that one of the natural modes, perhaps the most important natural
      mode, of transmission of kala-azar is from person to person by way of the upper
      respiratory and alimentary tracts. 6. Two normal human volunteers and numerous
      normal experimental animals have been inoculated into the nasal and oral cavities
      with the nasal discharge, known to contain leishmania, from patients with kala
      azar. The results of these experiments will be reported at a subsequent date.

PMID- 19870262
TI  - LYMPHOMATOSIS, MYELOMATOSIS, AND ENDOTHELIOMA OF CHICKENS CAUSED BY A FILTERABLE
      AGENT : II. MORPHOLOGICAL CHARACTERISTICS OF THE ENDOTHELIOMATA CAUSED BY THIS
      AGENT.
AB  - When stimulated by a filterable agent of leukosis of chickens (Strain 2),
      endothelium may undergo seemingly unrestricted growth. These neoplasms of
      endothelium are usually unaccompanied by the formation of blood cells.
      Occasionally they produce hemocytoblasts, discharged like those of the normal
      marrow into vascular channels as also myelocytes about the vessels. The same
      agent that stimulates endothelium also stimulates erythroblasts, myelocytes, and
      hemocytoblasts to unrestricted growth without obviously affecting the
      endothelium; and the association of endothelioma and leukosis is the result of
      stimulation of several types of cells by a single virus. Myelocytes appear also
      to develop from mesenchymal or endothelial cells without the intermediary stage
      of hemocytoblasts. It is often impossible to determine whether the neoplasms
      caused by the virus of Strain 2 are of endothelial or mesenchymal origin, and it
      is possible that both types of cells may be stimulated by the same virus. Types
      of sarcoma like those described by Rous are not produced by the virus of Strain
      2.

PMID- 19870263
TI  - QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION : THE ROLE OF MULTIPLE REACTIVE
      GROUPS IN ANTIGEN-ANTIBODY UNION AS ILLUSTRATED BY AN INSTANCE OF CROSS
      PRECIPITATION.
AB  - 1. Antisera to R-salt-azo-benzidine-azo-crystalline egg albumin give precipitates
      with crystalline egg albumin by virtue of their antidye content. 2. The
      quantitative course of the reactions with increasing amounts of antigen is very
      similar for the dye-antidye and egg albumin-anti-egg albumin systems, but differs
      markedly for the cross reaction between egg albumin and antidye. 3. A possible
      explanation for the occurrence of this one-sided crossreaction is given in terms
      of reactive groupings on the antigen and antibody. 4. A qualitative expression of
      the course of the cross-reaction is given in terms of the laws of classical
      chemistry.

PMID- 19870264
TI  - THE HISTOLOGY OF EQUINE ENCEPHALOMYELITIS.
AB  - The virus of equine encephalomyelitis (eastern strain) evokes in the horse, calf,
      sheep and dog an unusually intense encephalomyelitis characterized by acute
      primary degeneration of nerve cells, the appearance in neurons of the brain stem
      and elsewhere of nuclear inclusions resembling those in Borna disease and
      poliomyelitis, polymorphonuclear infiltration in the nervous tissues with early
      microglial proliferation, and perivascular cuffing with mononuclears and
      polymorphonuclears in varying proportions. The grey matter is affected more than
      the white. Lesions may be less marked in the striatum, brain stem and cord than
      in the cerebral cortex, thalamus and hypothalamic region, and are always of low
      grade in the cerebellum. Meningeal infiltration is secondary. Similar changes
      produced in the horse by the western strain of virus are less intense and
      extensive. In the guinea pig, rabbit and mouse, the eastern virus causes an acute
      encephalomyelitis which, as is usual in neurotropic virus diseases of these lowly
      species, has a special tendency to affect the higher olfactory centers. In
      addition to inclusions in the nerve cells, tiny oxyphilic bodies occur with less
      frequency in the glial and mesodermal nuclei of the guinea pig. In this animal,
      too, interstitial or bronchopneumonia may complicate the picture. In the guinea
      pig the disease resulting from infection with the western virus may be
      indistinguishable from that due to the eastern.

PMID- 19870265
TI  - FAILURE TO NEUTRALIZE THE POLIOMYELITIS VIRUS WITH SERA OF ADULT MACACUS RHESUS
      AND OF YOUNG FEMALE RHESUS TREATED WITH ANTERIOR PITUITARY EXTRACTS.
AB  - 1. Twelve specimens of serum from nine adult male monkeys failed to neutralize
      the virus of poliomyelitis. 2. Ten samples of serum obtained from three adult
      female monkeys at various phases of the menstrual cycle likewise proved incapable
      of neutralizing the virus. An eleventh serum, drawn from a fourth female 32 days
      postpartum, gave irregular results. It neutralized once and failed to do so on
      second test. This is the only suggestion in our experiments that a physiological
      factor may play a part in poliomyelitis immunity. 3. Fourteen sera from ten
      immature monkeys caused to menstruate by treatment with anterior pituitary
      extract were devoid of virucidal property. This treatment failed also to induce a
      systemic resistance to intracerebral injections of virus in the nine monkeys of
      the same group available for test. 4. We were unable to demonstrate in our
      monkeys a correlation between virucidal capacity of the serum and maturity or
      physiological variations as exemplified by menstruation.

PMID- 19870266
TI  - STUDIES ON MENINGOCOCCUS INFECTION : VI. THE CARRIER PROBLEM.
AB  - Of the three studies which have been reported in this paper, the most thorough
      and therefore the most instructive was that made upon the Rockefeller Institute
      group of 24 individuals. The ten carriers discovered in this group were found to
      fall into three categories; namely, chronic, intermittent and transient carriers.
      It is, perhaps, a matter for surprise, in view of the weight of evidence in the
      literature, that half of the carriers should appear in the chronic group, being
      constantly affected for periods over 2 years and continuing to carry throughout
      this period what was, to all tests, the same strain of microorganism. It has been
      shown that no claim of relief from the carrier condition can be based on three
      consecutive negative swabs at weekly intervals since apparent spontaneous
      "cures," as evidenced by negative swabs, may last for 4(1/2) months and finally
      be terminated by the reappearance of the same strain as that carried before. The
      effect of coryza and pharyngitis on the persistence and degree of the
      meningococcal infection has been studied and, while the results are scanty,
      indications have been found that coryza, unassociated with any increase in
      numbers of the nasopharyngeal pathogens or streptococci, causes no change in the
      number of meningococci present in the throat. On the other hand, a streptococcal
      pharyngitis or any infection in which other throat pathogens increase greatly in
      number is usually associated with a marked diminution or actual disappearance,
      whether temporary or permanent, of the meningococci from the nasopharynx. This is
      in accordance with the work of Colebrook and Gordon. Of the 26 carrier strains
      which were isolated in these three groups of individuals, only eight could be
      identified with Gordon's four types which are isolated from the majority of cases
      of meningitis. It is considered as certain, however, that the other 18 strains
      are to be regarded as true meningococci. Not only do they show the same cultural
      characteristics and fermentative reactions as the typical strains, but
      serological tests, especially that of absorption, have revealed that they are
      allied to the two main types, I-III and II, and can be regarded as belonging to
      the broad serological Groups I and II which include these typical Gordon types.
      Moreover, atypical Type II* strains, identical with those isolated from the
      nasopharynx of carriers, have recently been found to be the cause of two cases of
      frank cerebrospinal fever. Only five of the 26 strains belong to Group I while
      the other 21 are members of Group II. This is interesting in view of the work of
      Scott who found that Group II strains predominate in carriers during
      interepidemic periods like the present. In periods of epidemics the carrier
      strains from both contacts and noncontacts in the epidemic zone are more often of
      Group I and even more constantly tend to be of the typical Gordon types rather
      than atypical forms. As has been pointed out in an earlier paper (35), the
      viability of these carrier strains when planted in defibrinated rabbit blood is
      low as compared to the typical and freshly isolated meningitis strains. The exact
      significance of this fact is not known. It has not been possible up to the
      present to do comparative virulence tests between spinal fluid and nasopharyngeal
      strains owing to the absence of a sufficiently susceptible animal.

PMID- 19870268
TI  - THE CHARACTERS OF KUPFFER CELLS LIVING IN VITRO.
AB  - The Kupffer cells procured from the liver of the rabbit and dog for culture in
      vitro have the typical characters of clasmatocytes. They are readily
      discriminated from the monocytes washed from the liver with them; and they have
      certain peculiar features which suffice to differentiate them from some at least
      of the clasmatocytes of other organs. Their surface is extraordinarily sticky,
      far more so than that of blood leukocytes or of the clasmatocytes found in
      peritoneal exudates; and in consequence they are exceedingly difficult to handle
      in vitro. They put forth enormous, pellucid, circular membranes resembling those
      of exudate clasmatocytes but larger. Splenic clasmatocytes, on the other hand,
      put forth rather small, one-sided ground-glass membranes like broad tongues. On
      comparing them with Kupffer cells and exudate clasmatocytes one perceives that
      they are not wholly identical in their characters, but have secondary
      peculiarities. However, there exist good morphological reasons for grouping them
      together and terming them all reticulo-endothelial. Kupffer cells are notably
      sensitive to injury, surviving in Tyrode solution for a much shorter time than
      blood leukocytes. However, they can be readily cultured on lens paper in serum.
      Under such circumstances they scatter on the fibres and live separately,
      presenting the same general aspect as when in the liver; but in the course of
      proliferation they soon lose some of their pronounced characters, retaining such
      as are common to clasmatocytes in general. A considerable population of ordinary
      leukocytes exists in the hepatic sinuses over and above those circulating in the
      blood. During infection, their number may greatly increase. Several cubic
      centimeters of packed white cells have been obtained from the liver of a sick
      dog. The fact has been realized that leukocytes may stop a while in the liver,
      yet the extent of the accumulation which sometimes takes place seems deserving of
      stress.

PMID- 19870267
TI  - SELECTION WITH THE MAGNET AND CULTIVATION OF RETICULO-ENDOTHELIAL CELLS (KUPFFER
      CELLS).
AB  - Methods and apparatus are described where with living Kupffer cells can be
      procured from the liver of the rabbit and the dog for study and cultivation in
      vitro. Almost none of these cells can be dislodged from the normal liver by
      forcible perfusion; but after they have taken up finely particulate matter (India
      ink, iron oxide), they come away in great numbers. When they have phagocyted
      ferromagnetic iron oxide they can be selected with a magnet from amongst the
      blood elements present in suspension with them; and they are obtainable in
      quantity by this means. They do poorly when plated in a thin plasma clot, failing
      to multiply or to assume their characteristic shape; but they flourish when
      allowed to attach themselves to strands of lens paper bathed in serum that is
      frequently changed. Bacterial infection of serum cultures of Kupffer cells from
      normal rabbits and dogs occurs only as the result of secondary contamination of
      the materials, whereas it regularly develops in cultures from animals with fever
      induced by the injection of nucleic acid or of killed B. prodigiosus. Kupffer
      cells obtained under such conditions are abnormally active, and some can be
      washed out of the liver of sick animals in the absence of any preliminary
      phagocytosis of particulate matter. The facts have a bearing both on the
      conditions conducing to blood invasion and on the response of the Kupffer cells
      in the emergency. The characters of the isolated Kupffer cells and the results of
      tests of their presumptive functions will be described in later papers.

PMID- 19870270
TI  - EXPERIMENTAL TYPE III PNEUMOCOCCUS PNEUMONIA IN MONKEYS : II. TREATMENT WITH AN
      ENZYME WHICH DECOMPOSES THE SPECIFIC CAPSULAR POLYSACCHARIDE OF PNEUMOCOCCUS TYPE
      III.
AB  - The effects of specific enzyme therapy upon experimental Type III pneumococcus
      pneumonia in monkeys were studied by comparing the course and outcome of the
      disease in treated animals with that in animals which received no therapeutic
      aid. Enzyme treatment was found to exert a distinctly favorable influence upon
      the experimental pneumonia. Treatment was followed by cessation of spread of the
      pneumonic lesion, sterilization of the blood, and early recovery, except in
      animals in which the severity of the disease was extreme. While in the untreated
      animals a high incidence of empyema and pericarditis was observed, suppurative
      sequelae were apparently prevented by adequate enzyme therapy. The limitations of
      the therapeutic action of the specific enzyme in the presence of marked
      depression of the cellular reaction in infected animals are again emphasized.

PMID- 19870269
TI  - EXPERIMENTAL TYPE III PNEUMOCOCCUS PNEUMONIA IN MONKEYS : I. PRODUCTION AND
      CLINICAL COURSE.
AB  - It has been possible by the intratracheal or intrabronchial inoculation of Type
      III Pneumococcus to produce in monkeys of the M. cynomolgos species an
      experimental pneumonia which in its clinical aspects closely resembles
      pneumococcus lobar pneumonia in man. The experimental disease is characterized by
      the development of a well localized pulmonary lesion of lobar distribution which
      tends to spread, the frequent occurrence of septicemia, a sustained fever, and
      the termination of the infection after a variable interval, in recovery or death
      of the animal. Wide variations in the severity of the disease in different
      monkeys have been noted. These variations appear to be due primarily to
      differences in the resistance of individual animals. The height of the septicemia
      accompanying the experimental pneumonia has been found to be the most valuable
      objective index of the probable outcome of the disease. Other factors which may
      influence the course and outcome of the disease are discussed.

PMID- 19870271
TI  - LOUPING ILL IN MAN.
AB  - Four instances of infection in man which are believed, because of the
      circumstances under which they occurred and in view of the results of
      neutralization tests, to represent cases of louping ill have been described.
      Evidence obtained by the neutralization tests is in favor of the idea that the
      antibodies against louping ill virus demonstrated in certain sera were most
      likely the result either of contact with or of infection with the active agent.

PMID- 19870272
TI  - THE EFFECT OF CARROT FEEDING ON THE SERUM PROTEIN CONCENTRATION OF THE RAT.

PMID- 19870273
TI  - THE EFFECT OF A GROWTH-PROMOTING EXTRACT OF THE ANTERIOR PITUITARY ON THE EARLY
      GROWTH OF THE ALBINO RAT.
AB  - Castrate male albino rats were injected with a growth-promoting extract of bovine
      anterior pituitary from the 21st day of life (day of castration) to the 56th day
      (average for group) at which time the difference in weight between the pituitary
      injected animals and controls was first clearly discernible. In comparison to
      controls the pituitary-injected animals at this stage showed: (1) a decrease in
      the weight of the pituitary gland; (2) an increase in nose-anus length; (3) an
      increase in the weight of heart, lungs, liver, and kidneys which is shown to be
      of the nature of a splanchnomegaly; (4) an increase in the weight of the blood
      removed; (5) an increase in the water content of the skin and the kidneys; (6) a
      tendency toward an increase in weight of the carcass. The significance of these
      findings is discussed.

PMID- 19870274
TI  - OBSERVATIONS ON THE BLOOD CYTOLOGY IN EXPERIMENTAL SYPHILIS : I. THE PERIOD OF
      DISEASE ACTIVITY.
AB  - Weekly observations were made on the blood cytology of seven syphilitic and nine
      normal control rabbits. Each animal was examined seven times prior to and fifteen
      times after inoculation of the experimental group. Comparisons were made between
      the mean blood cell values obtained from all counts on the experimental and
      control groups in the preinoculation and postinoculation periods. The mean blood
      cell formula of the syphilitic group for the 3(1/2) month period after
      inoculation was significantly different from the preinoculation mean values
      observed in the same group in the following respects: higher total white cell
      count, platelet count, neutrophil count, and monocyte count, and lower lymphocyte
      count. The mean blood cell formula of the syphilitic group for the 3(1/2) month
      period after inoculation was significantly different from the mean blood cell
      formula of the normal control group in the same time interval in the following
      respects: higher total white cell count, platelet count, neutrophil and monocyte
      counts, and lower lymphocyte count. From these results it was concluded that
      during the period of disease activity, the blood cytology of rabbits infected
      with Tr. pallidum is characterized by an increase in the total white cell count,
      the platelet, neutrophil, and monocyte counts, and a decrease in the lymphocyte
      count from normal values. These changes were statistically significant.

PMID- 19870275
TI  - OBSERVATIONS ON THE BLOOD CYTOLOGY IN EXPERIMENTAL SYPHILIS : II. THE PERIOD OF
      DISEASE LATENCY.
AB  - The mean blood cell levels of 35 latent syphilitic rabbits in which all lesions
      had undergone spontaneous regression and complete healing were compared with
      weighted values for normal rabbits. The only differences noted were in the red
      cell count and hemoglobin content, both of which were significantly lower in the
      experimental group than the normal values. A parallelism was observed between the
      blood cell changes of the experimental disease after spontaneous regression of
      lesions, and the cell changes in the human disease after treatment. This
      parallelism lends additional weight to deductions drawn from the experimental
      disease as applied to human syphilis.

PMID- 19870276
TI  - STUDIES ON PSEUDORABIES (INFECTIOUS BULBAR PARALYSIS, MAD ITCH) : II. ROUTES OF
      INJECTION IN THE RABBIT, WITH REMARKS ON THE RELATION OF THE VIRUS TO OTHER
      VIRUSES AFFECTING THE NERVOUS SYSTEM.
AB  - After intramuscular, intradermal and subcutaneous inoculation, the pseudorabies
      virus reaches the central nervous system by way of the peripheral nerves,
      although it is circulating in the blood. Centrifugal spread from the infected
      nervous tissues by the neural route also occurs. After intracerebral inoculation
      the virus passes in the reverse direction, down the nervous axis. The Aujeszky
      strain invades the blood stream more readily than does the Iowa strain; but
      possibly with repeated passage the latter is approximating in this respect more
      closely the classical Aujeszky strain. After intravenous inoculation, effective
      with even small doses, virus is rapidly removed from the blood, and multiple
      infective foci are established in various organs; thence ascent of the virus by
      the peripheral nerves leads to infection of the central nervous system, the
      symptomatology differing according to whether the spinal cord or the medulla is
      first reached. The lack of evidence that the virus can penetrate directly the
      hemato-encephalic barrier deserves emphasis. When subcutaneous inoculation is
      practised in an area deprived of its nerve supply, the ability of the virus to
      invade the blood stream permits it to establish infective foci in the various
      viscera, and, after a predictable delay, the course of infection resembles that
      following intravenous injection. The pseudorabies virus is pantropic; i.e., it
      readily attacks cells derived from any embryonic layer. Lesions in the adrenal
      gland following intravenous inoculation are very like those due to herpes virus
      similarly introduced, this being one point of similarity in the pathogenic action
      of the two organisms. The relation of the pseudorabies virus to other viruses
      affecting the central nervous system is discussed.

PMID- 19870277
TI  - SEROLOGICAL STUDIES ON AZOPROTEINS : ANTIGENS CONTAINING AZOCOMPONENTS WITH
      ALIPHATIC SIDE CHAINS.
AB  - A study was made of the specificity of artificial compound-antigens containing
      aliphatic chains. Striking specificity was exhibited in the reactions of
      compounds with short chains containing a carboxyl group; for instance succinic
      acid could be differentiated from malonic or glutaric acid which contain one
      fewer and one more carbon atom respectively. With the substances containing
      longer chains, reactions were observed which, although specific to a certain
      extent, appear to depend mainly on the general physicochemical properties of long
      aliphatic chains. With a limited number of substances the influence of
      substituents -halogen, OH, NH(2)-on the serological specificity was investigated.
      By means of inhibition reactions it was possible to demonstrate the serological
      specificity of cis-trans isomers such as maleic and fumaric acid.

PMID- 19870278
TI  - ON THE SEROLOGICAL SPECIFICITY OF PEPTIDES. II.
AB  - In continuation of previous studies immune sera for azoproteins made from
      aminobenzoyl dipeptides and tripeptides were tested with various peptide
      azoproteins by precipitin tests and with nitrobenzoyl derivatives of peptides by
      means of inhibition reactions. When examined with the latter method, the immune
      sera exhibited a high degree of specificity and permitted the recognition of
      distinctions among peptides of similar structure.

PMID- 19870279
TI  - EPIDEMIC TREMOR, AN ENCEPHALOMYELITIS AFFECTING YOUNG CHICKENS.
AB  - A new disease having a characteristic and well defined symptom complex is
      described as occurring in young chickens in four New England states. Tremor,
      principally of the head and neck, and progressive ataxia are the characteristic
      symptoms, either or both of which may be present in a single bird. Age at onset
      in field epidemics ranges from 3 days to 6 weeks, with a majority of cases
      reported at 3 weeks. Morbidity in commercial flocks ranges from 5 to 50 per cent;
      mortality in affected hatches may be 50 per cent. The disease may or may not
      recur in successive hatches, and in the same flock in successive years. Although
      birds may survive an attack of the disease, nervous symptoms persist in a
      majority of cases. There is no evidence that nutritional factors are involved.
      Normal chickens have not contracted the disease by contact with affected birds.
      The disease has been reproduced in normal chickens by intracerebral inoculation
      of brain and spinal cord from affected birds. Twenty brain-to-brain passages have
      been made up to the present time. The incubation period in laboratory passages
      ranges from 6 to 44 days with symptoms appearing usually between 21 and 28 days.
      The proportion of inoculated birds developing symptoms has increased with
      successive passages. The infective agent in the brain has survived in 50 per cent
      glycerine for 69 days. No organism has been cultivated. The disease has been
      reproduced after inoculation with bacteriologically sterile filtrates obtained
      with Seitz and Berkefeld N filters. Attempts to demonstrate the presence of the
      infective agent in the chicken embryo have been inconclusive. Chicks hatched from
      eggs laid by birds which had survived the disease were not infected, nor were
      they immune to inoculation at 6 weeks of age. The characteristic lesion of the
      disease consists of microscopic focal collections of glia cells, perivascular
      infiltration, degeneration of Purkinje's cells, and degeneration of nerve cells.
      Foci of infiltration are present throughout the brain and spinal cord. In the
      viscera of birds from field epidemics, microscopic focal infiltrations of cells
      of the lymphoid series are often found. Their presence is most notable in the
      pancreas and heart. No cell inclusions have been demonstrated.

PMID- 19870280
TI  - THE PRODUCTION OF STREPTOCOCCUS HEMOLYTICUS BACTEREMIA IN NON-SPECIFICALLY
      SENSITIZED ANIMALS.
AB  - Rabbits sensitized to horse serum developed a bacteremia of 9 to 12 hours'
      duration when they were inoculated simultaneously with normal horse serum and a
      strain of Streptococcus hemolyticus, while the bacteria could only be isolated
      from the blood stream of non-sensitized animals within the first 3 hours after
      inoculation. On the other hand, when antisera are employed as the antigen for
      shocking the sensitized rabbits, there is a significant increase in the number of
      bacteria in the blood stream in contrast to the control animals, but there is no
      evidence of a prolongation of the bacteremia.

PMID- 19870281
TI  - STUDIES ON THE ETIOLOGY OF SPONTANEOUS CONJUNCTIVAL FOLLICULOSIS OF RABBITS : I.
      TRANSMISSION AND FILTRATION EXPERIMENTS.
AB  - Spontaneous conjunctival folliculosis is widespread among various species of
      rabbits. It exists in two forms: Type I, in which the lesions are localized and
      the disease is relatively inactive, and Type II, in which the follicles are
      closely distributed over the entire surface of the conjunctivae and the affection
      is more active and characterized by extensive inflammatory reactions. One type
      can be converted into the other either by experimental methods or by natural
      processes. The disease can be transmitted from rabbit to rabbit by means of
      subconjunctival inoculation of suspensions of the affected tissues or by
      instillation of such material into the conjunctival sac, or even by mere contact
      of folliculosis animals with rabbits having smooth conjunctivae. It is plain that
      the disease is an infection. The causal agent of the infection is not filtrable
      through Seitz discs that retain Serratia marcescens nor through Berkefeld V
      candles that permit the passage of this organism. Furthermore, the lesions of the
      spontaneous or of the experimental disease do not exhibit the cytotropic effects
      or the inclusion bodies suggestive of the action of an ultramicroscopic virus.
      They are characterized, on the other hand, by a persistent and progressive
      chronicity and show certain resemblances to the granulomata. The evidence
      suggests that the spontaneous conjunctival folliculosis of rabbits is due to a
      microorganism-one having a low grade pathogenic action. In a paper shortly to be
      published, a bacterium capable of reproducing folliculosis in normal rabbits will
      be described.

PMID- 19870282
TI  - THE ANTIGENIC RELATIONSHIP BETWEEN PROTEUS X-19 AND TYPHUS RICKETTSIA : II. A
      STUDY OF THE COMMON ANTIGENIC FACTOR.
AB  - A soluble specific substance was isolated from Mexican typhus Rickettsia which
      gave, with Proteus X-19 antiserum and typhus human serum, the same precipitation
      reactions as the polysaccharides extracted from B. proteus OX-19. The soluble
      specific substance extracted from Rickettsia and Proteus OX-19 is likely to be of
      a polysaccharide nature owing to the strong Molisch reactions obtained with such
      extracts, the heat stability and the negative protein reactions (biuret). Since,
      however, it still contains 7 per cent nitrogen, this is not certain. In the
      antigenic composition of both Proteus X-19 and typhus Rickettsia there is a
      common soluble specific factor which is responsible for the Weil-Felix reaction.

PMID- 19870283
TI  - STUDIES ON HOST FACTORS IN PNEUMOCOCCUS INFECTIONS : II. THE PROTECTIVE ACTION OF
      TYPE I ANTIPNEUMOCOCCUS SERUM IN RABBITS.
AB  - The power of specific antipneumococcus serum to protect rabbits against infection
      with Type I Pneumococcus has been studied with reference to the capacity of the
      animal to utilize the specific antibodies. Under conditions ensuring relatively
      controlled genetic factors it was found that heavier animals and those with high
      white blood cell counts are much better able to utilize the passively conferred
      immune principles. The interrelationships of the extrinsic and intrinsic factors
      responsible for immunity have been discussed.

PMID- 19870284
TI  - PATHOLOGIC HISTOLOGY OF THE SHWARTZMAN PHENOMENON WITH INTERPRETATIVE COMMENTS.
AB  - The histological study of the reaction to injection of the preparatory factor of
      the Shwartzman phenomenon shows it to be an exudative inflammation, but furnishes
      no conclusive evidence as to whether or not the inflammation is conditioned by
      previous sensitization to substances contained in the bacterial filtrate. The
      histological study of the local reaction which follows the intravenous injection
      of reacting or provocative factor shows exudative inflammation which differs from
      that due to the preparatory factor principally in the increased general severity
      and marked damage to blood vessels. The increased severity of reaction which
      follows the intravenous injection is probably due to concentration of the
      injurious agent at the site of inflammation determined by the preparatory local
      injection. The exudative phenomena caused by the preparatory local injection are
      edema and infiltration of polymorphonuclear leucocytes and large mononuclear
      cells. Vascular injury is morphologically demonstrable in only a few of the
      sections, notably those from periarticular structures. The intravenous injection
      determines an increase in cellular infiltration, necrosis of exudate,
      phagocytosis of cell debris, destruction of vascular walls and hemorrhage.
      Healing is due to granulation, organization and cicatrization.

PMID- 19870285
TI  - THE INFECTION OF FERRETS WITH SWINE INFLUENZA VIRUS.
AB  - The experiments described confirm the earlier observation of Smith, Andrewes, and
      Laidlaw that the swine influenza virus is pathogenic for ferrets when
      administered intranasally. A disease that is clinically more severe and
      pathologically more extensive than that described by the above workers is
      obtained if inoculation with the virus is performed under ether anesthesia.
      Animals infected in this way show at autopsy an edematous type of pneumonia of
      lobar distribution which may terminate fatally. The virus maintains its
      pathogenicity for ferrets when stored in 50 per cent glycerol at refrigerator
      temperature for as long as 75 days. After serial passage through 16 ferrets the
      virus is still capable of inducing swine influenza when mixed with H. influenzae
      suis and administered intranasally to swine. Ferret passage causes no apparent
      attenuation of the virus for swine. Serum from pigs recovered from swine
      influenza is capable of neutralizing the ferret-passaged virus for either swine
      or ferrets. Likewise serum from recovered ferrets neutralizes the swine influenza
      virus for either ferrets or swine.

PMID- 19870286
TI  - THE FLOW AND COMPOSITION OF LYMPH IN RELATION TO THE FORMATION OF EDEMA.
AB  - 1. The experimental observations have been summarized at the end of an earlier
      section. The more important facts only will be recapitulated here. The capacity
      of the lymphatics for removing fluid from the tissues greatly exceeds the rate at
      which freshly formed tissue fluid can be made available for removal. Edematous
      regions can be rendered non-edematous by the application of measures, such as
      massage, passive motion, or normal exercise, which activate the lymphatics.
      During continuous activity the rate of lymph flow is first variable and later
      relatively constant. Constant rates of flow must correspond to the production of
      fresh lymph. A study of the constant rates indicates that lymph formation in the
      edematous animal is certainly only slightly greater, and possibly not greater at
      all, than under conditions of normality. When the protein of plasma decreases,
      the protein of lymph is also lowered. The loss of protein from lymph takes place
      at a faster rate than from plasma, so that the ratio of serum protein to lymph
      protein is greater in the edematous than in the normal animal. In edematous
      animals the concentration of protein in lymph is of the same order of magnitude
      as the concentration in edema fluids. The two fluids are not, however, identical
      in composition. Minor fluctuations in the protein content of lymph always occur
      during a period of continuous collection. 2. The factors involved in the
      circulation and accumulation of tissue fluid are discussed. Reasons are given for
      offering the following suggestions. Significant differences in tissue pressure or
      tension exist between the states resulting from quiescence and activation of the
      lymphatics. The differences give rise to variations in the relative areas of
      capillary wall, functioning for filtration and reabsorption. When the lymphatics
      are activated it is possible that capillary reabsorption may be completely in
      abeyance. A decline in the proteins of plasma may be associated with a diminished
      permeability of the capillaries. Such a lowering of capillary permeability would
      account for two features, both of which have been demonstrated: (1) failure to
      observe an appreciably increased rate of lymph formation in the edematous animal,
      and (2) the extremely low concentration of protein in lymph from edematous
      animals. Although the difference between the protein concentrations of edema
      fluid and lymph from the same region is small, the conclusion is not yet
      justified that a similarly small difference exists between normal tissue fluid
      and normal lymph.

PMID- 19870287
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : VIII. THE
      INFLUENCE OF THE ACETYL GROUP ON THE SPECIFICITY OF HEXOSIDE-PROTEIN ANTIGENS.
AB  - The chemical and immunological properties of the acetylated and unacetylated
      forms of the p-aminophenol beta-glucoside of glucose have been described. The
      serological specificity of these beta-glucosides in combination with protein has
      been correlated with known changes in chemical structure and has been compared
      with the immunological properties of the alpha-glucoside of the same hexose.

PMID- 19870288
TI  - STUDIES ON HOST FACTORS IN PNEUMOCOCCUS INFECTIONS : I. CERTAIN FACTORS INVOLVED
      IN THE CURATIVE ACTION OF SPECIFIC ANTIPNEUMOCOCCUS SERUM IN TYPE I PNEUMOCOCCUS
      DERMAL INFECTION IN RABBITS.
AB  - In the experimental disease brought about by infecting rabbits intradermally with
      Type I Pneumococcus the use of relatively small or subeffective amounts of
      specific antipneumococcus serum leads to the survival of some individuals and the
      death of others. It has been shown that both the severity of the infection and
      the white blood cell count are factors in the determination of the outcome of the
      disease but that there remain other host factors which have to do with the
      utilization or functioning of the specific antisera.

PMID- 19870289
TI  - THE RESPIRATION MECHANISM OF PNEUMOCOCCUS. III.
AB  - From an examination of Tables I to III, and Figs. 1 to 4 and the consideration of
      various observations, the following facts are evident. A virulent pneumococcus on
      being transformed into its-avirulent form consumes many times more oxygen than
      the parent organism; but this gain of activity is a temporary property. After a
      time it degenerates into a form which consumes very much less oxygen than either
      the virulent or the recently derived avirulent form. In a comparative study of
      the metabolic functions, and oxidation products of various virulent and avirulent
      pneumococci, these phenomena should receive consideration. The change that takes
      place in the structure of the enzyme responsible for carbohydrate biosynthesis
      during the shift from the virulent to the avirulent form may be associated with
      the changes in the enzyme structure already demonstrated in connection with these
      metabolic studies.

PMID- 19870290
TI  - AN IMMUNOLOGICAL STUDY OF THE A SUBSTANCE OR ACETYL POLYSACCHARIDE OF
      PNEUMOCOCCUS TYPE I.
AB  - 1. The A carbohydrate isolated from Type I pneumococcus by Pappenheimer and
      Enders, on the basis of elementary analysis, the presence of the acetyl group and
      its immunological properties, appears to be identical with the acetyl
      polysaccharide described by Avery and Goebel. 2. The A carbohydrate possesses a
      greater anti-opsonic action than either the deacetylated substance obtained by
      boiling in alkali or the soluble specific substance of Type I pneumococcus
      prepared according to the procedure of Heidelberger, Goebel and Avery. The
      opsonic titre of normal human serum is practically eliminated upon the addition
      of the A carbohydrate-an effect not observed with equivalent amounts of either
      the deacetylated material or the specific soluble substance. In immune serum, the
      A carbohydrate brings about a quantitatively greater reduction in opsonic
      activity than its derivatives, but it has not been possible to demonstrate
      complete inhibition of phagocytic action by the method of absorption of antibody.
      3. In a system of normal human serum and leucocytes capable of destroying Type I
      pneumococcus, the bactericidal effect maybe entirely removed upon the addition of
      the A carbohydrate. It proved impossible to inactivate the bactericidal action
      with the deacetylated substance in equivalent proportions. In this system, the A
      carbohydrate was about 64 times more effective as an antibactericidal agent than
      the deacetylated compound. Essentially similar results were obtained in a study
      of the antibactericidal properties of the A carbohydrate and the deacetylated
      derivative in the presence of anti-Type I pneumococcus rabbit serum added to a
      mixture of exudative leucocytes and the defibrinated blood of the rabbit. 4. The
      mouse-protective titre of anti-Type I pneumococcus rabbit serum is lowered to a
      greater degree after absorption with the A carbohydrate than it is by similar
      treatment with the deacetylated compound. Absorption with the A carbohydrate does
      not, however, completely remove the protective antibody. 5. As Avery and Goebel
      have shown in the case of the acetyl polysaccharide, so the A carbohydrate, when
      administered in very small quantities, protects mice against an otherwise fatal
      dose of Type I pneumococcus. Active immunity in mice has been obtained with as
      little as 0.00005 mg. of the A carbohydrate administered in a single dose. Doses
      larger than 0.005 mg. confer no protection on these animals. Deacetylization of
      the A carbohydrate after boiling in N/10 sodium hydroxide destroys its protective
      capacity while similar treatment in N/50 alkali does not completely remove its
      immunizing property. Active immunity may arise within 3 days following a single
      injection of the A substance. It appears to be at its height from 6 to 25 days
      thereafter, and is retrogressive by the 49th day following vaccination. Injection
      of the A carbohydrate into immunized mice immediately before infection deletes
      the state of resistance. 6. The immunity actively induced as a result of
      injection of the A carbohydrate may be passively transferred to normal mice with
      the serum of vaccinated animals. 7. Since the evidence obtained in the course of
      this study indicates that the A carbohydrate of Type I pneumococcus and the
      acetyl polysaccharide of Avery and Goebel represent the same chemical substance,
      it is suggested that the designation "A carbohydrate" or "A substance" be
      relinquished in favor of the more exactly descriptive term "acetyl
      polysaccharide."

PMID- 19870291
TI  - VARYING INFLUENCE OF TUBERCULOUS RABBIT PLASMA ON THE GROWTH OF FIBROBLASTS IN
      VITRO.
AB  - Plasma obtained from tuberculous rabbits within 3 or 4 months following
      inoculation with bovine tubercle bacilli exerted a growth-inhibitory influence on
      transplants of rabbit fibroblasts; while that obtained after the 4th month was
      growth-stimulating. It is suggested that the growth-inhibitory factor was linked
      in part with lipoidemia; while the growth-stimulating elements were associated
      with the period of leucocytosis.

PMID- 19870292
TI  - THE FATE OF BCG AND ASSOCIATED CHANGES IN THE ORGANS OF RABBITS.
AB  - For some time after intravenous inoculation into rabbits the BCG multiplies in
      various organs of the body. As with more virulent tubercle bacilli, the greater
      the primary deposition of bacilli the more rapid is their initial growth and the
      earlier is the beginning of their destruction. Destruction sets in synchronously
      with the development of definite hypersensitivity to tuberculin. With the
      smallest deposition destruction begins at once in the lung and liver without
      preliminary multiplication. However multiplication always takes place in the
      lymph nodes. It continues here and in the spleen at a time when other organs have
      acquired sufficient immunity to reduce the number of bacilli considerably. It is
      seen that the relative susceptibility of the lymphatic tissue is not due to such
      factors as drainage. Thus the local immunity acquired by the lymph nodes against
      the BCG is for a time less effective than that developed in the other organs.
      However by the end of the 4th week, simultaneously with the development of marked
      hypersensitivity to tuberculin, even these structures acquire sufficient immunity
      to bring about the all but complete annihilation of the bacilli. Isolated
      microorganisms persist in the lymph nodes even 14 months after inoculation. These
      bacilli do not acquire any added virulence because of their long residence in the
      body. As observed with more virulent strains in previous studies, the growth of
      the bacilli is associated with a local accumulation of mononuclears into nodules
      and their multiplication by mitosis, the destruction of the bacilli with the
      formation of epithelioid and giant cell tubercles. These changes may be extensive
      and at times involve a large part of the lung and lymph nodes. The secondary
      invasion of the tubercles by polymorphonuclears, their death, exudation of serum
      and cells into the alveoli of the lung, and caseation in the lymph nodes occur
      simultaneously and are synchronous with the development of hypersensitiveness to
      tuberculin. At this time the presence in the tissues of numbers of bacilli that
      previously were innocuous to the cells is associated with caseation. It is
      noteworthy that both caseation and the tuberculin reaction are not elicited in an
      early stage of the disease, but in a later stage they are induced in response to
      smaller quantities of bacilli or tuberculin. All the tuberculous changes,
      including the caseous foci in the lymph nodes, usually resolve completely by the
      end of the 2nd month after inoculation without leaving any fibrous scars,
      although perivascular accumulations of mononuclears may still remain. The few
      bacilli that persist in the lymph nodes after this period cause no tuberculous
      changes.

PMID- 19870293
TI  - RESULTS OF IRRADIATING STAPHYLOCOCCUS AUREUS BACTERIOPHAGE WITH MONOCHROMATIC
      ULTRAVIOLET LIGHT.
AB  - The incident energies required to kill Staphylococcus aureus or to inactivate its
      homologous bacteriophage have been measured at the various wave-lengths of the
      quartz mercury vapor arc between 238 and 302 mmicro and found to run strictly
      parallel, the readings for the S. aureus phage being obtained at a uniformly
      higher energy level. This difference in levels is of less significance than the
      striking similarity in the shapes of the energy curves, which indicate that in
      both instances the same organic structures are absorbing the radiations. The
      results are open to three interpretations. The most obvious is that the
      bacteriophage is a submicroscopic organism. Again, it is possible that the
      bacteriophage is a product of its own lytic action on the homologous bacterium
      and contains the essential structural units which in S. aureus also are destroyed
      by ultraviolet light and thus cause the death of the organism. A third, more
      remote explanation is that the phage, of wholly unknown nature, is absorbed on S.
      aureus material in so intimate a bond that the alteration of this material by
      irradiation renders the phage incapable of further lytic activity.

PMID- 19870294
TI  - FATE OF BILIRUBIN IN THE SMALL INTESTINE.
AB  - Since there was no loss of bilirubin from the jejunal loop, and no loss of
      bilirubin when pigment was incubated with juice from the loop segment, or juice
      from the entire small intestine, it may be concluded that the intestinal juice
      per se has no effect in converting bilirubin to urobilin in a 2 hour period, and
      that in the jejunal loop there was no absorption of pigment or no conversion to
      urobilin. The experiments showing loss of pigment in the entire intestinal tract
      suggest that in some place other than the jejunal portion of the intestine the
      combined activity of intestinal contents and intestinal cells does affect the
      bilirubin in the intestine. Whether the loss of bile pigment under such
      circumstances is due entirely to conversion, or to conversion and absorption, or
      to absorption of bilirubin as such, remains to be answered by subsequent
      investigations.

PMID- 19870295
TI  - TRANSPLANTATION OF TOOTH GERM ELEMENTS AND THE EXPERIMENTAL HETEROTOPIC FORMATION
      OF DENTIN AND ENAMEL.
AB  - The formation of dentin and enamel in the abdominal wall in young pups was
      achieved by transplantation of the soft tissues of the developing tooth germ. An
      interesting finding was the cytomorphosis of the epithelium of the enamel organ.
      When this was transplanted so that the ameloblasts were in contact with the
      odontoblasts the cylindrical character of the epithelial cells was preserved and
      enamel was produced; otherwise the cylindrical shape of these cells was lost and
      a stratified epithelium resulted, resembling the gingival and certain tumors (the
      adamantinoma) of the jaw and related structures. This degenerated epithelium did
      not produce enamel and had an important characteristic of not forming cysts in a
      closed connective tissue space, instead forming islands and cords of cells with
      epithelial pearl formation. Thus the influence of mesodermic connective tissue
      derivatives on the form and function of epithelium is presented. The odonto
      blasts were found capable of survival as such and readily formed new dentin in
      transplantation; the stellate cells of the pulp were inert from the standpoint of
      inducing calcification.

PMID- 19870296
TI  - VACCINATION OF MONKEYS AND LABORATORY WORKERS AGAINST PSITTACOSIS.
AB  - Monkeys that have recovered from psittacosis pneumonia have an increased
      resistance to infection with the virus and possess neutralizing antibodies in
      their sera. Large amounts of active psittacosis virus can be introduced
      intravenously and intramuscularly into monkeys without the production of a
      serious infection such as pneumonia. Relatively small amounts of virus introduced
      intratracheally into monkeys usually lead to psittacosis pneumonia. Monkeys
      vaccinated intramuscularly with unattenuated psittacosis virus have an increased
      resistance to the active agent and possess neutralizing antibodies in their sera.
      The intramuscular introduction of active psittacosis virus in moderate amounts
      into human beings is relatively harmless, and repeated inoculations lead to the
      appearance of neutralizing antibodies in the sera of vaccinated individuals.

PMID- 19870297
TI  - BIOCHEMICAL STUDIES ON THE FIBRINOLYTIC ACTIVITY OF HEMOLYTIC STREPTOCOCCI : I.
      ISOLATION AND CHARACTERIZATION OF FIBRINOLYSIN.
AB  - THE ACTIVE FIBRINOLYTIC PRINCIPLE PRESENT IN CULTURES OF HEMOLYTIC STREPTOCOCCI
      CAN BE ISOLATED IN STABLE FORM, AND PARTIALLY PURIFIED BY THE FOLLOWING METHODS:
      1. Precipitation of culture filtrate with 3 volumes of 95 per cent ethyl alcohol.
      2. Adsorption upon polyaluminum hydroxide B of Willstatter (5) followed by
      elution with M/10 sodium phosphate buffer, pH 7.3. Concentration can be best
      accomplished by vacuum dialysis (4) of either culture filtrates or preparations
      obtained by adsorption and elution. The streptococcal fibrinolysin is
      characterized by the following properties: 1. It may resist heating to 100
      degrees C. for 60 minutes; variations in thermal resistance are described. 2.
      Partially purified preparations give positive tests for protein. Activity is
      rapidly and completely destroyed by trypsin or papain. 3. The active principle is
      demonstrable in dissolved fibrin even after 18 hours incubation.

PMID- 19870298
TI  - BIOCHEMICAL STUDIES ON THE FIBRINOLYTIC ACTIVITY OF HEMOLYTIC STREPTOCOCCI : II.
      NATURE OF THE REACTION.
AB  - The fibrinolysin of hemolytic streptococci exerts no hydrolytic action upon
      casein, gelatin, or peptone. The action on solid human fibrin is characterized by
      a small and gradual increase in the amino nitrogen content of the solution. The
      specific and special enzymatic action of fibrinolysin is contrasted with trypsin
      and with streptococcal peptase (4). Solutions of human fibrinogen, after brief
      incubation with fibrinolysin, lose the capacity to form fibrin. Solutions of
      rabbit fibrinogen, on the other hand, retain the property of transformation into
      fibrin, even after prolonged exposure to fibrinolysin. Qualitative tests, with
      solutions resulting from the action of streptococcal fibrinolysin on human
      fibrin, indicate that the end-product may be protein and that the degradation of
      the molecule is not great.

PMID- 19870299
TI  - THE FATE OF AVIRULENT HEMOLYTIC STREPTOCOCCI INJECTED INTO THE SKIN OF NORMAL AND
      SENSITIZED RABBITS : LOCAL FIXATION OF BACTERIA.
AB  - 1. A relatively avirulent strain of hemolytic streptococci injected into the skin
      of normal rabbits seldom diminished and usually increased in number during the
      first 5 hours after inoculation but after 12 hours save in exceptional instances
      the organisms diminished rapidly and disappeared. 2. Hemolytic streptococci
      injected into the skin of normal rabbits passed rapidly from the site of
      injection to the regional lymph nodes from which they were recovered in
      considerable number within 15 minutes. Passage of bacteria from the skin of the
      abdomen to the inguinal lymph node was greatest within 2 hours after injection
      and gradually decreased so that few organisms were recovered from the lymph nodes
      after 7 hours. 3. Hemolytic streptococci that reached the inguinal lymph node
      passed in small numbers to the distal or iliac lymph node, but this passage save
      in exceptional instances of progressive infection was limited to a period within
      1 hour after inoculation. 4. Avirulent hemolytic streptococci injected into the
      skin of normal animals penetrated into the blood; they were seldom recovered from
      the circulating blood but were more frequently found in the spleen. 5. When
      hemolytic streptococci were injected into the skin of sensitized rabbits they
      multiplied at the site of injection during the first 5 hours after inoculation
      and at corresponding time intervals a larger number of organisms were recovered
      from the sensitized than from normal control animals. Streptococci diminished and
      disappeared earlier from the skin of control than from that of sensitized
      rabbits. 6. Hemolytic streptococci injected into the skin of the flank of
      sensitized rabbits reached the inguinal lymph node in much smaller numbers than
      in normal rabbits, and this passage from the site of injection to the lymph node
      save in an occasional instance of progressive local infection ceased after the
      1st hour. No streptococci passed from the inguinal to the iliac lymph nodes of
      sensitized animals and none were found in the blood or internal organs. 7.
      Histological examination showed that the inflammatory reaction following the
      injection of hemolytic streptococci into rabbits sensitized to this organism
      began sooner than in the normal animal; edema was more extensive and both
      polymorphonuclear leucocytes and large mononuclear cells appeared sooner. The
      lesion of a sensitized animal was more sharply circumscribed and there was
      necrosis of tissue, seldom seen in the normal animals. 8. In sensitized animals
      local injury with necrosis favors the multiplication of relatively avirulent
      streptococci at the site of entry and explains their survival at a time when they
      have disappeared in the controls. 9. In association with greater local injury and
      a more intense inflammatory reaction in the sensitized animal as compared with
      the normal streptococci are fixed at their site of entry; they pass to adjacent
      lymph nodes in much smaller number and fail to reach the blood and internal
      organs.

PMID- 19870300
TI  - THE MATERNAL TRANSMISSION OF VACCINIAL IMMUNITY IN SWINE : II. THE DURATION OF
      ACTIVE IMMUNITY IN THE SOW AND OF PASSIVE IMMUNITY IN THE YOUNG.
AB  - The protective substances produced by vaccinia virus in swine are transmitted
      repeatedly to the young by way of the colostrum of the sow. In 2 instances
      suckling immunity was demonstrable in the young of 6 successive farrowings which
      numbered 37 and 57 individuals, respectively. The immunity acquired by suckling
      began to decline during the 2nd month and was practically negligible by the end
      of the 3rd month. Vaccinia virus introduced cutaneously during the first few days
      of life in the passively protected pigs exerted little or no immunizing effect.

PMID- 19870301
TI  - A FACTOR FROM NORMAL TISSUES INHIBITING TUMOR GROWTH.
AB  - Extracts of desiccated embryo skin and placenta have been found to exert a
      definite retarding action on the growth of two transplantable carcinomas of mice,
      but they were without effect on sarcomas. In tests involving some 828
      inoculations of the tumor cells and the extracts, complete suppression of growth
      occurred in from 55 to 71 per cent of instances, as compared with 21 to 27 per
      cent in the controls, and where growth was not completely suppressed some
      retardation was found in practically every instance. To judge from findings in
      rabbits the inhibitor is not demonstrable in the placenta until the beginning of
      the second third of pregnancy, reaches its maximum by the last third, but
      disappears about 2 or 3 days before term. Extracts of fresh placenta are without
      effect, and no very definite inhibition was noted in extracts of a variety of
      other desiccated or fresh tissues. The conclusions here reported are based on the
      results of over 3800 inoculations.

PMID- 19870302
TI  - THE EFFECT OF A GROWTH-RETARDING FACTOR FROM NORMAL TISSUES ON SPONTANEOUS CANCER
      OF MICE.
AB  - Extracts of desiccated homologous embryo skin and placenta decrease markedly the
      rate of postoperative local recurrence after the surgical removal of spontaneous
      cancer of mice. Autografts after a short period of contact with these extracts
      either failed to grow, or, in the majority of instances, their subsequent growth
      was definitely retarded. Intraperitoneal injection of the extracts was followed
      by cessation of growth of established tumors in more than two-thirds of the
      animals treated, and among these many of the tumors regressed and over 20 per
      cent were completely absorbed. Tumor mice treated with either extract rarely
      developed new malignant foci, though this happened frequently in untreated mice.

PMID- 19870303
TI  - THE SURVIVAL OF VARIETIES OF TYPHUS VIRUS IN MOUSE PASSAGE, WITH PARTICULAR
      REFERENCE TO THE VIRUS OF BRILL'S DISEASE.
AB  - The experiments above described have confirmed the observations of Laigret and
      Jadin that the European human typhus virus cannot be maintained for more than two
      generations in mice by brain-peritoneum passage; whereas the murine Mexican
      variety can be carried on by this method in mice through at least eleven passage
      generations. The fact that within eleven passages there is no attenuation of the
      murine virus renders it likely that this agent can continue in mice, in an
      inapparent form, without material modification. Brill's disease virus from three
      different isolations has behaved like the European type, a fact which strengthens
      the opinion previously expressed from this laboratory that Brill's disease
      represents an imported European strain of the classical European infection.

PMID- 19870304
TI  - THE EFFECT OF ANTECEDENT INFECTION AND IMMUNIZATION WITH STREPTOCOCCI UPON THE
      REACTIVITY OF RABBITS TO HORSE SERUM.
AB  - 1. The cutaneous responses of rabbits to small doses of horse serum
      intracutaneously is described. After an original injection of 0.1 cc. a secondary
      reaction often occurs about the 9th day, and tests at 3 day intervals with 0.001
      cc. quantities indicate that general skin hypersensitivity is established at this
      time. Circulating precipitins for horse serum appear later. As the degree of
      sensitivity increases, lesions resulting from test doses reach a maximum
      development more quickly. 2. The reactivity of rabbits to horse serum is greatly
      increased by antecedent sensitization of the animals with repeated small
      intracutaneous inoculation of indifferent streptococci or immunization with large
      intravenous injections of either indifferent or hemolytic streptococci. Doses of
      indifferent streptococci precisely comparable to those producing greatly enhanced
      reactivity when given intracutaneously, increase reactivity to horse serum
      irregularly and to slight degree when injected intravenously. 3. Increases in
      reactivity (allergic irritability) are made evident by the occurrence of larger
      skin lesions at the site of the primary horse serum injections, the earlier
      development of more distinct secondary reactions in a higher percentage of
      animals, and by the more rapid appearance of skin sensitivity to the small test
      doses which may be first evidenced by delayed reactions at these injection sites.
      Accompanying these evidences of increased reactivity, there is an early
      appearance of blood serum precipitins in high titer. 4. There was no evidence of
      residual inflammation in any of the animals at the time reactivity to horse serum
      was tested. No attempt was made to determine the duration of this altered
      reactive capacity. It has been encountered in tests begun from 8 to 14 days after
      the last preliminary inoculation. 5. It is suggested that the increased reaction
      described is brought about by a persisting alteration in the functional activity
      of the reticulo-endothelial system.

PMID- 19870305
TI  - THE INFLUENCE OF SEXUAL MATURITY UPON THE REACTIVITY OF RABBITS TO HORSE SERUM.
AB  - 1. Normal rabbits in the course of their development, after infancy, vary in
      their responses to minute doses of horse serum given intracutaneously. 2. There
      is increased reactivity in males as they mature, beginning, in the stock employed
      in these experiments, at about the age of 13 weeks when a weight of 1,700 gm. has
      been attained. 3. The reactivity of normal females remains at a constant level
      and the increase demonstrated in males does not take place. 4. The divergence in
      degree of reactivity between males and females, beginning with the establishment
      of estrus, indicates that factors associated with sexual maturity in females are
      responsible for their low reactivity. 5. The suppression of estrus by operative
      removal of the ovaries results in an increase of reactivity which, however, in
      the experiments reported here is probably not great enough to account entirely
      for the difference in reactivity between mature males and females.

PMID- 19870306
TI  - STUDIES ON ORGANOGENESIS : I. THE ABILITY OF ISOLATED BLOOD CELLS TO FORM
      ORGANIZED VESSELS IN VITRO.
AB  - 1. Isolated blood cells, when placed for incubation in a plasma substratum, are
      capable of constructing highly organized, tubular processes that project from the
      explanted cell mass into the surrounding medium. 2. The tubular structures have
      fibrillar walls that may be covered, eventually, by a membranous layer of
      leukocytes. Their lumina contain blood cells suspended in fluid. 3. The formation
      of the tubules is initiated by the red cells. The leukocytes, and more
      particularly the thrombocytes, are responsible for the construction of the walls.
      4. The phenomenon occurs only in the presence of plasma, the coagulation of which
      has been slightly delayed. Once the surrounding medium has become firmly
      coagulated, no further change occurs either in the length of the tubules or in
      their diameter. 5. The development of the tubules is not suppressed by substances
      that enhance cellular activity unless they induce, at the same time, the
      immediate coagulation of the medium. The addition of embryo tissue juice prevents
      their formation by producing early coagulation. 6. The phenomenon as a whole is
      dependent upon the physicochemical nature of the medium, the character and
      thickness of the explanted fragment, and the physical and physiological
      peculiarities of the cells that comprise it. It is the expression of various
      physicochemical and physiological events that have occurred in a definite order,
      or sequence.

PMID- 19870307
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : IX. THE EFFECT OF AQUEOUS
      EXTRACTS OF CHICKEN TUMOR I ON YEAST NUCLEIC ACID.
AB  - 1. Aqueous extracts of Chicken Tumor I cause a disintegration of yeast nucleic
      acid. 2. Two enzyme activities, a polynucleotidase and a phosphatase, are
      demonstrated. 3. These activities are distinguished by different reactions to an
      environment of hydrogen, different optima of hydrogen ion concentration, and
      different rates of activity. 4. Adsorption with aluminum hydroxide Type C removes
      substances inhibiting the polynucleotidase activity. 5. There is a rough
      proportionality between the polynucleotidase activity and the tumor-inducing
      power of different fractions of extracts of Chicken Tumor I. 6. There is a rough
      proportionality between the inhibition of polynucleotidase activity and the
      inhibition of the tumor agent. 7. The polynucleotidase activity of Chicken Tumor
      I is as great as that of spleen, slightly less than that of kidney and liver, but
      much greater than that of muscle. There are also qualitative differences.

PMID- 19870308
TI  - STUDIES ON THE ETIOLOGY OF SPONTANEOUS CONJUNCTIVAL FOLLICULOSIS OF RABBITS : II.
      BACTERIOLOGICAL INVESTIGATIONS.
AB  - Before summarizing the experimental results presented herewith, a brief review is
      indicated of our study on follicular conjunctivitides existing in the different
      species of animals thus far examined. Spontaneous follicular conjunctivitis of
      monkeys and chimpanzees, which resembles the early, or follicular, stages of
      human trachoma, has been shown to be an infectious disease, and to arise from the
      action of a bacterium and not an ultramicroscopic virus (2, 10). A new species of
      organism, designated tentatively as Bacterium simiae, n.sp., and capable of
      reproducing granular lids in normal monkeys and apes, has been recovered from
      cultures of simian folliculosis tissues. This organism, although of a different
      species, is of the same genus as Bacterium granulosis which is associated with
      human trachoma (3). The studies were extended beyond folliculosis in monkeys and
      apes to a similar disease widespread among stock rabbits. Its clinical appearance
      and microscopic changes resemble the spontaneous malady in simians with some
      minor differences (1). Like the latter, rabbit folliculosis was also shown to be
      infectious and contagious. In the present paper a bacteriological investigation
      of the rabbit affection is described. In the experiments undertaken we followed
      the method used by Noguchi in his studies on trachoma, that is, the different
      organisms recovered from normal and affected conjunctivae were inoculated into
      the conjunctivae of selected, quarantined rabbits. Among the bacteria thus
      isolated from folliculosis tissue a new species was disclosed that brought about
      conjunctival reactions apparently indistinguishable either from the disease seen
      in nature or from the experimental infection induced by inoculation of
      folliculosis tissue. The organism was specifically active in rabbits whether
      injected subconjunctivally or instilled into the conjunctival sac. Furthermore,
      the special bacterium has thus far been cultivated only from folliculosis cases
      and not from other forms of conjunctivitis nor from normal tissues. Finally,
      specifically pathogenic strains of the identical microorganism have been
      recovered from rabbits experimentally infected with the bacterium. A distinctive
      feature of this bacterium is that it is of the same genus as the microorganisms
      heretofore designated as Bacterium granulosis and Bacterium simiae. It is clearly
      evident then that the three bacteria cultivated to this time form a new genus,
      for which we propose the name Noguchia. The diagnosis of the genus has already
      been described in this paper, but as was also shown in a foregoing section,
      certain specific characters differentiate the three. Accordingly, we suggest a
      change in the names of the granulosis and simiae species to the proposed
      binomials, Noguchia granulosis, n.sp., and Noguchia simiae, n.sp. The specific
      organism, having an evident causal relationship to rabbit folliculosis, can
      therefore be placed in this classification, with the name of Noguchia cuniculi,
      n.sp. In conclusion it would appear that in three types, at least, of follicular
      reactions in the conjunctiva-in man (the primary lesion of trachoma consisting
      essentially of follicles), in the simian, and in the rabbit-there is an intimate
      association of microorganisms having the same generic, but different specific
      properties.

PMID- 19870309
TI  - BACTERIOLOGICAL STUDIES ON AN EPIZOOTIC OF INTESTINAL DISEASE IN SUCKLING AND
      NEWLY WEANED MICE.
AB  - It is now quite generally conceded that the presence in animals of bacteria of
      Salmonella type is indicative of an active, or potentially active, pathogenic
      agent (26). In the present instance bacteriological studies of the organs of
      acutely ill infant mice revealed the presence of one of the Salmonella group. It
      showed itself to be such by an absence of fermentation of lactose and saccharose,
      by other cultural reactions, and by cross-agglutination with certain members of
      the Salmonella group in very low dilutions of their antisera.(6) However, the
      bacterium cannot be included in any of the known species of the group because of
      its indol-forming properties, differences in carbohydrate reactions, and specific
      serological reactions. Its presence in affected mice, growth on artificial media,
      ability to cause the disease following enteral and parenteral inoculations, and
      the fact that it can be recovered from artificially infected mice fulfill the
      postulates of Koch. Furthermore, agglutinins are present in the blood of
      recovered mice and not in that of normal animals, and recovery of mice from
      natural infection evokes an apparent resistance against the special recovered
      Salmonella bacterium. The organism would appear to fall in the Asiaticusdivision
      of the genus, as designated by Castellani and Chalmers (27).

PMID- 19870310
TI  - THE METABOLISM OF COPPER AND IRON IN SPLENECTOMIZED RATS FREE FROM BARTONELLA
      MURIS INFECTION.
AB  - Removal of the spleen in albino rats free from Bartonella muris infection is
      followed by an increased elimination of copper in the feces, which commences 2
      weeks after splenectomy. This is associated with a persistent negative copper
      balance. An increased retention of iron occurs during a period of 4 to 6 weeks
      after splenectomy with a return of the iron metabolism to normal after this
      period. No disturbance in creatine or creatinine metabolism occurs. The uric acid
      amount is unchanged. There is an increase in the retention of nitrogen, which is
      first noted 3 weeks after splenectomy. The spleen is essential for the
      utilization of copper in the body.

PMID- 19870311
TI  - STUDIES ON WHOOPING COUGH : I. TYPE-SPECIFIC (S) AND DISSOCIATION (R) FORMS OF
      HEMOPHILUS PERTUSSIS.
AB  - The more important criteria for identification of the S form of H. pertussis and
      for its differentiation from R variants are presented in summary fashion in Table
      IV. The differences as indicated in detail in the foregoing sections and as shown
      briefly in this tabulation are so clear-cut that they call for little, if any,
      further comment. Of all the differential characteristics, the morphological, the
      serological, and the cataphoretic seem to be the most distinctive, and of these,
      the cataphoretic, in our hands, has been the most conclusive. It would appear
      from the foregoing results that all recently isolated strains, provided that they
      are grown upon suitable media, fall into a single uniform serological type. This
      is true whether the strains are isolated from cases of whooping cough in Europe
      or in any part of this country. It is also apparent that when they are
      subcultured upon laboratory media deficient in fresh blood, dissociation occurs
      with the appearance of morphologically, culturally, and antigenically different
      variants. In keeping with the current classification of bacterial variants, we
      feel that the uniform recently isolated strain should be designated the S form
      and the laboratory variants the R form of H. pertussis. Whether the R variants
      fall into sharply defined phases as pointed out by Leslie and Gardner, remains to
      be confirmed. Lawson and the writer have never noted their "Phase II" and Toomey
      (21) is in agreement with us that sharply defined, mutually exclusive
      subvarieties of R variants probably do not exist. We are undertaking further
      studies of this somewhat mooted point. Dawson, as a result of detailed studies
      concerned with the dissociation of pneumococci (22) and of streptococci (23) has
      shown that these organisms have three variant forms and he proposes that the
      terminology currently employed for pneumococcal variants be changed to conform
      with the terms used in the description of corresponding variants of other
      bacterial species. The first form, encapsulated, at present called S, he
      designates mucoid (M); the second, at present R, he calls smooth (S); and the
      third, a new and distinct, grossly rough variant which he describes for the first
      time,l he would call rough (R). Hadley (24) has found that most organisms show
      these three chief colony forms. From conversation with Dr. Dawson, it seemed that
      our S which is encapsulated and has a moist mucoid colony has the character of
      his M form. Whether the subvarieties of R variants (III and IV of Leslie and
      Gardner, A and B of Mishulow) correspond to his S and R, remains to be seen. For
      the time being it has seemed more practical to use the terms S and R as generally
      employed. As we study H. pertussis variants further, it is possible that these
      three chief colony forms, constituting the usual pattern for other bacterial
      species, may emerge as well defined types. The finding that H. pertussis when
      first isolated is a single specific serological type, in S form, and that this
      antigenic phase may be maintained by suitable cultural management has certain
      definite implications. One bears upon further transmission experiments directed
      toward the establishing of the etiological relationship of the organism to
      whooping cough. Working with monkeys, Sauer (25) produced suggestive
      manifestations of the disease in 8 out of 76 attempts. It is very probable that
      his failures may be laid to the use of R forms as inoculum. Criticism directed
      against the conclusiveness of the occasional successful transmission experiment
      (Sauer (25), Rich et al. (26), MacDonald and MacDonald (27)) with freshly
      isolated H. pertussis put forward by those entertaining the combined H. pertussis
      and filtrable virus theory is being met in the experiments already reported upon
      (4) and still being carried out in this laboratory, by subculturing the
      theoretically pathogenic S form long enough to preclude the presence of virus. A
      second implication of importance related to the preparation of H. pertussis
      vaccines. Madsen (28), Sauer (29), and Frawley (30), the last worker using
      Krueger's specially prepared H. pertussis vaccine (31), have recently reported
      favorably regarding protection against whooping cough by means of suitably
      prepared vaccines. Sauer following the lead of Madsen insists upon the use of
      freshly isolated organisms; Krueger's special vaccine is made from similar
      strains. The ready identification of the S form of H. pertussis and the
      practicability of its maintenance brought out above puts the preparation of
      antigenically effective vaccines upon a sound basis. In cooperation with Dr. J.
      A. Doull of the Department of Hygiene and Bacteriology and Dr. H. J.
      Gerstenberger of the Department of Pediatrics, we have begun a carefully
      controlled study of the prophylactic value of H. pertussis vaccines made from
      organisms shown to be in the S form according to the criteria outlined above. By
      the same token, the therapeutic value of H. pertussis vaccine in active cases of
      the disease can be determined only after carefully controlled studies have been
      carried out with such antigenically effective preparations.

PMID- 19870312
TI  - A COMPARISON OF OCULAR MICROMETRIC AND PROJECTOSCOPIC METHODS OF ESTIMATING
      GROWTHS IN TISSUE CULTURES.
AB  - In estimating the increments of growth of tissue cultures and of comparative
      indices it is possible to use areas calculated from measurement of two axes made
      with an ocular micrometer in an ordinary microscope. On the assumption that the
      growths are approximately circular in outline the squares of their radii are used
      as the factors for comparison. Results obtained with this method agree fairly
      closely with those derived from projectoscopic drawings and planimetric
      measurements.

PMID- 19870313
TI  - RABBIT POX : I. CLINICAL MANIFESTATIONS AND COURSE OF DISEASE.
AB  - The clinical manifestations and course of a highly contagious and acutely fatal
      disease designated as rabbit pox have been described. The general symptomatology
      of this infection varies within wide limits and accurate diagnosis rests on the
      occurrence of certain characteristic lesions. The most distinctive sign of
      infection is a pock-like eruption which is often outspoken and widespread over
      the body, but is sometimes poorly defined and detectable only after careful
      physical examination. Other lesions depend upon the involvement of particular
      organs and give rise to special symptoms. As a rule, the incubation period of the
      epidemic infection varies between 5 and 7 days. No evidence of the transmission
      of the infection by recovered animals could be obtained. Furthermore, breeding
      tests demonstrated that the reproductive capacities of most animals were not
      permanently impaired.

PMID- 19870314
TI  - RABBIT POX : II. PATHOLOGY OF THE EPIDEMIC DISEASE.
AB  - The lesions found in animals with epidemic rabbit pox have been described in this
      paper. The most distinctive gross lesion in all organs and tissues was the small
      nodule or papule which was found to consist of mononuclear infiltration and
      necrosis. Diffuse lesions were also found in which the infiltration was
      widespread and accompanied by edema, hemorrhage and extensive necrosis of
      affected tissues and organs. The possibility of the diffuse lesions being due to
      the action of secondary invaders was considered, but available evidence indicated
      that the different types, including pneumonia, represented reactions to a single
      causative agent. Moreover, an intimate relationship was observed to exist between
      lesions and small blood vessels in which primary endothelial damage was usually
      apparent. The degree of vascular damage generally corresponded to the extent of
      the lesion and it is probable that this in turn corresponded to the dose of the
      causative agent. The close analogy between the clinical manifestations and
      pathological processes of this disease in the rabbit and small pox in man led to
      the conclusion that the disease in the rabbit is essentially the same as small
      pox, and that it is probably produced by a virus closely related to the virus of
      small pox. Available evidence indicated that the infection originated in the
      Institute and that it spread in atypical form or masked by some other disease
      until it reached the breeding colony as a clearly defined epidemic infection.

PMID- 19870315
TI  - ON THE EXISTENCE OF A FACTOR INCREASING TISSUE PERMEABILITY IN ORGANS OTHER THAN
      TESTICLE.
AB  - Many of the organs from animals of both sexes, including the ovary, have been
      found to contain in various proportion a factor or factors increasing tissue
      permeability. The potency exhibited by such active extracts was always less than
      that of extracts from testicle. Blood serum was found to be devoid of any
      spreading property.

PMID- 19870316
TI  - THE ACCUMULATION OF IRON IN TUBERCULOUS AREAS : IV. THE EFFECT OF FERRIC CHLORIDE
      ON THE COURSE OF TUBERCULOSIS IN REINFECTED RABBITS.
AB  - Repeated intravenous injections of dilute ferric chloride solution in tuberculous
      rabbits markedly retard the development of the disease as evidenced both by a
      prolongation in the survival time and by comparison of lesions in control and
      experimental animals. Partial immunity induced by first infection combined with
      ferric chloride administration enhances in reinfected animals even more
      strikingly the favorable effects of the iron salt. Some of the experimental
      animals were still alive and apparently well about 6 months after the death of
      the last of the controls which succumbed about 4 months after reinfection with
      virulent tubercle bacilli. Factors that may perhaps account for the favorable
      effect of ferric chloride in experimental tuberculosis have been discussed.

PMID- 19870317
TI  - THE PARTICIPATION OF SKIN LYMPHATICS IN REPAIR OF THE LESIONS DUE TO INCISIONS
      AND BURNS.
AB  - With the aid of solutions of vital dyes the lymphatic capillaries in the ear of
      the mouse have been studied during the period of immediate reaction to injuries
      of various sorts and during the period of repair. The behavior of lymphatics
      severed by incision differs greatly from that of the small blood vessels. Instead
      of closing they sometimes remain open for as long as 48 hours. Materials
      introduced into the wound pass directly into the lymphatics through their gaping
      ends, a fact which will explain why infection from incisions is predominantly
      along the lymphatics. All around an injury the lymphatics are rendered abnormally
      permeable. So, too, are the blood vessels, a fact well recognized in the past.
      Twenty-four to 48 hours later, at a time when the blood vessels in the edematous
      tissue surrounding the injured area are still much more permeable than normal,
      the draining lymphatics allow far less to escape than usual. The possible reasons
      for this have been discussed. The lymphatics participate in the removal of fluid
      from the edematous tissue. As repair after injury takes place severed lymphatics
      may reunite when as yet there are no functioning blood vessels. Later an active
      hyperplasia of the lymphatic channels occurs, an extraordinarily abundant plexus
      of minute lymph capillaries budding into the area under repair.

PMID- 19870318
TI  - IRREVERSIBLE CHARACTER OF THE LATE CHANGES AFTER HEPATECTOMY.
AB  - The symptoms of advanced liver insufficiency, in the hepatectomized rabbit, are
      irreversible. That is to say, cross-transfusions between liverless rabbits and
      normal ones fail to ameliorate the symptoms of liver deprivation once they are
      established. The normal rabbits show no symptoms suggesting that toxic substances
      have accumulated in the blood of the hepatectomized ones.

PMID- 19870319
TI  - BIOLOGICAL STUDIES OF THE TUBERCLE BACILLUS : III. DISSOCIATION AND PATHOGENICITY
      OF THE R AND S VARIANTS OF THE HUMAN TUBERCLE BACILLUS (H(37)).
AB  - 1. The H(37) strain of human tubercle bacillus has been dissociated into two
      variants,-the R, or avirulent, and the S, or virulent, variants. 2. When their
      dissociation is complete, colony morphology for each is distinctive and typical.
      3. The morphology of the individual bacilli of the two variants is different and
      characteristic. 4. The R variant develops best in an acid medium; the S develops
      best in an alkaline medium. 5. A method of assortment to facilitate the procedure
      of forced dissociation has been described. 6. The difference in virulence has
      been proven by observations on the pathogenesis of the variants.

PMID- 19870320
TI  - THE PROTECTIVE ACTION OF COPPER AGAINST TRYPANOSOMA EQUIPERDUM INFECTION IN
      ALBINO RATS.
AB  - The effect was studied of additions of copper to an adequate diet on the course
      of infection with Trypanosoma equiperdum in rats. Copper in amounts equivalent to
      0.2 mg. of elemental copper per rat per day during a period of 10 days prior to
      an induced infection with small numbers of trypanosomes raised the natural
      resistance of the rat to the infection. The infection was aborted in all
      instances when the rats were infected by the injection of 2,000 trypanosomes and
      in 75 per cent of instances when the rats were infected by the injection of
      10,000 trypanosomes.

PMID- 19870321
TI  - STUDIES ON MOUSE LEUKEMIA : XI. METABOLIC EFFECTS OF HOST CONSTITUTION.
AB  - 1. Two highly inbred strains of mice of different genetic constitution (Storrs
      Little and C58) were used in a study of the influence of hosts on metabolism of
      cells of transmissible lymphatic leukemia. The experiments were carried out with
      leukemic cells of transmission Line I as well as with Line M-liver. About 50 per
      cent of the Storrs-Little mice were killed by each line of cells at this time,
      while 100 per cent of the C58 mice were killed. 2. The normal lymphoid tissues of
      the two strains of mice were significantly the same in regard to rates of oxygen
      consumption and both aerobic and anaerobic glycolysis. 3. Leukemic cells of Line
      I, growing in hosts of Strain Storrs-Little, gave significantly lower rates of
      aerobic and anaerobic glycolysis than when growing in hosts of Strain C58. Oxygen
      consumption was significantly higher. Leukemic cells of Line M-liver, growing in
      hosts of Strain Storrs-Little, gave significantly lower rates of aerobic and
      anaerobic glycolysis than when growing in Strain C58. Oxygen consumption was not
      significantly different. 4. After one to three passages through hosts of Strain
      Storrs-Little, the cell lines were returned to hosts of Strain C58, with
      immediate return to significantly the same metabolic rates originally given by
      each line in hosts of Strain C58. 5. These results lead to the more general
      conclusions that: (a) The genetic constitution of the host modifies the
      metabolism of the cell line. (b) The same host constitution may modify the
      metabolism of different cell lines in different ways. (c) Host constitution does
      not appear to modify the inherent constitution of the leukemic cells, but acts as
      a determining environmental factor on their metabolism.

PMID- 19870322
TI  - THE ANTIBODY RESPONSE OF RABBITS TO INJECTIONS OF EMULSIONS AND EXTRACTS OF
      HOMOLOGOUS BRAIN.
AB  - Rabbits injected with fresh emulsions of homologous brain developed few or no
      antibodies capable of fixing complement in the presence of aqueous emulsions or
      alcoholic extracts of rabbit brain. Complement-fixing antibodies, however, were
      produced in rabbits by means of injections (1) of sterile emulsions of homologous
      brain which had been allowed to stand at room temperature for 5 to 30 days and
      (2) of emulsions of homologous brain experimentally infected with vaccine virus.
      The antisera that were produced following injections of emulsions of autolyzed
      homologous brain were shown by absorption tests to contain both specific and non
      specific antibodies. The specific brain antigen was found to be approximately six
      times as abundant in the white matter as in the grey. It was almost absent from
      the brain of fetal and newly born rabbits, but increased in amount with the age
      of the animal to reach a maximum concentration at maturity. The specific antigen
      seemed to parallel the myelin content of brain tissue.

PMID- 19870323
TI  - A THERMOPRECIPITATION REACTION IN TRYPANOSOMA EQUIPERDUM INFECTION IN LABORATORY
      ANIMALS.
AB  - There is a thermoprecipitinogenic substance in extracts of the spleen of rats,
      guinea pigs and rabbits infected with T. equiperdum. It does not appear to be
      within the body of the trypanosome itself. Antibodies to this heat-resistant
      precipitable substance were found in the serum of infected animals. The antibody
      strength seems to be relatively less in the serum of rats than in the other
      animals but the power of extracts from the spleen of infected rats appeared to be
      equivalent to the power of similar extracts of the other animals. The antibody
      titer of the serum of rabbits was greater than in the case of the other two
      species investigated. This was shown not only by the reaction with the extracts
      of spleens of the same species, but also by the reaction with extracts of the
      spleens of similarly infected animals of other species.

PMID- 19870324
TI  - A STUDY ON THE MECHANISM OF INVASIVENESS OF STREPTOCOCCI.
AB  - 1. Menkin's observations of the failure of inflammatory fixation in areas of
      acute inflammation due to Streptococcus haemolyticus have been confirmed. 2. The
      lack of inflammatory fixation in the presence of streptococci is not due to the
      passive nature of the streptococcus, but may be attributed to the production of
      (1) fibrinolytic, and (2) antifibrinogenic substances which dissolve the fibrin
      barrier, or prevent its formation, thus maintaining the patency of the lymphatics
      and capillaries and facilitating the dissemination of the organisms. 3. The
      production of fibrinolytic or antifibrinogenic substances, and the invasiveness
      of a given strain of streptococcus are correlative. 4. Both substances are
      relatively thermostable. Fibrinolysin is destroyed if held at 100 degrees C. for
      1 hour. The antifibrinogenic substance is weakened but is not destroyed under the
      same conditions. 5. There is evidence that both substances are antigenic, and
      exhibit some degree of type specificity. 6. The role of fibrinolysin and the
      antifibrinogenic factor in the invasion of the tissues by streptococci is
      discussed.

PMID- 19870325
TI  - CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : IX. THE
      SPECIFICITY OF ANTIGENS PREPARED BY COMBINING THEp-AMINOPHENOL GLYCOSIDES OF
      DISACCHARIDES WITH PROTEIN.
AB  - The results of the present study indicate that by means of serological reactions
      it is possible to differentiate selectively the p-aminophenol glycosides of
      maltose, cellobiose, gentiobiose, and lactose. The immunological specificity of
      disaccharide-protein antigens prepared from these derivatives, irrespective of
      the nature of the conjoined protein, is determined by (1) the glycoside molecule
      as a whole, (2) the configuration of the terminal hexose molecule, and (3) the
      position of linkage of the two hexose units in the carbohydrate radical. The
      specificity of the antibodies induced by the disaccharide antigens appears to be
      more sharply defined when the configuration of the terminal hexose is of the beta
      rather than of the alpha type.

PMID- 19870326
TI  - STUDIES UPON MINUTE HEMOLYTIC STREPTOCOCCI : I. THE ISOLATION AND CULTURAL
      CHARACTERISTICS OF MINUTE BETA HEMOLYTIC STREPTOCOCCI.
AB  - The cultural and biochemical characteristics of a group of minute hitherto
      undescribed beta hemolytic streptococci from human sources have been recorded and
      upon the basis of these cultural reactions it is suggested that these organisms
      may represent new species of the genus streptococcus.

PMID- 19870327
TI  - STUDIES UPON MINUTE HEMOLYTIC STREPTOCOCCI : II. THE DISTRIBUTION OF MINUTE
      HEMOLYTIC STREPTOCOCCI IN NORMAL AND DISEASED HUMAN BEINGS.
AB  - 1. Minute beta hemolytic streptococci were found to occur from one-third to one
      half as frequently in normal individuals as do ordinary beta hemolytic
      streptococci. 2. They were rarely isolated from the rhinopharynges of individuals
      suffering from chronic disease. 3. In acute respiratory tract infection other
      than that due to the ordinary beta hemolytic streptococcus the incidence of
      minute streptococci was slightly higher than in normal individuals. 4. In acute
      streptococcal infections, scarlet fever and acute tonsillitis, for example, the
      incidence of minute hemolytic streptococci did not significantly vary from the
      incidence found in normal human beings. 5. Minute beta hemolytic streptococci
      were found in the throats of 33 out of 42 patients ill with glomerular nephritis
      and in 25 out of 59 patients who were suffering from the various manifestations
      of rheumatic fever. 6. In glomerular nephritis and rheumatic infection the minute
      beta hemolytic streptococci were isolated from the throats of more patients than
      were the ordinary beta hemolytic streptococci.

PMID- 19870328
TI  - CHEMICAL STUDIES ON BACTERIAL AGGLUTINATION : I. A METHOD.
AB  - 1. A method, conforming to the criteria of quantitative analytical chemistry, is
      described for the estimation of the agglutinin content of antisera. Examples are
      given of the application of the method to various antipneumococcus sera. 2. This
      new, absolute method is discussed with regard to its relation to the commonly
      used relative methods.

PMID- 19870329
TI  - THE PROTECTION AFFORDED BY VACCINATION AGAINST SECONDARY INVADERS DURING COLDS IN
      INFANCY.
AB  - All intensive course of vaccination with the pathogenic bacteria of the upper
      respiratory tract modified favorably the winter outbreak of severe respiratory
      disease in an infant population. The incidence of the common cold was not
      affected. The significance of these findings is discussed.

PMID- 19870330
TI  - HEMORRHAGES IN SKIN LESIONS OF GUINEA PIGS FOLLOWING INTRAVASCULAR INJECTION OF
      TOXINS (SHWARTZMAN PHENOMENON).
AB  - 1. Filtrates from B. coli, B. typhosus, or meningococci injected into the skin of
      guinea pigs do not produce visible inflammation. When these injections are
      followed by intravascular injections of the same material, hemorrhages do not
      occur in the skin. 2. Guinea pigs sensitized to horse serum react with redness
      and edema to 0.1 or 0.01 cc. of horse serum injected into the skin, and
      subsequent intravascular injection of typhoid filtrate does not produce
      hemorrhage at the site of the reaction to horse serum. 3. When guinea pigs are
      injected into the skin with diphtheria toxin and these injections are followed by
      intravascular injection of filtrates from B. typhosus, hemorrhage occurs in the
      skin at the site of the reaction to diphtheria toxin. 4. When silver nitrate is
      injected into the skin of guinea pigs, redness, edema, and necrosis follow, and
      in a few guinea pigs small areas of hemorrhage can also be noticed. About half of
      the guinea pigs that have received an intravascular injection of typhoid filtrate
      react with hemorrhage at the site of the injection of silver nitrate.

PMID- 19870331
TI  - HEMORRHAGES IN TUBERCULOUS GUINEA PIGS AT THE SITE OF INJECTION OF IRRITANTS
      FOLLOWING INTRAVASCULAR INJECTIONS OF INJURIOUS SUBSTANCES (SHWARTZMAN
      PHENOMENON).
AB  - 1. When toxic filtrates from cultures of B coli, B. typhosus, or meningococci are
      injected into the blood stream, peritoneal cavity, or subcutaneous tissue of
      tuberculous guinea pigs, the skin at the site of a tuberculin reaction becomes
      hemorrhagic. The extent of the hemorrhage is proportional to the severity of the
      tuberculin reaction demonstrable by tests with various dilutions of tuberculin.
      2. Tuberculin does not prepare the skin of non-tuberculous guinea pigs for this
      hemorrhagic reaction. 3. Tuberculin does not produce an intense or necrotic
      inflammation in the skin of tuberculous rabbits and fails to prepare the skin for
      the hemorrhagic reaction. 4. Tuberculin injected into the peritoneal cavities of
      tuberculous guinea pigs causes a hemorrhage in the skin at the site of a
      tuberculin reaction. 5. All guinea pigs infected with B.C.G., and most of those
      infected with a virulent strain of tubercle bacilli, when sensitized to horse
      serum and injected intracutaneously with 0.1 cc. of horse serum, react with
      redness, edema, and necrosis; and in some instances the necrosis is preceded by
      hemorrhage. When horse serum is injected into the skin of these guinea pigs in
      such dilution that only redness and edema result, the subsequent intravascular
      injection of typhoid filtrate produces hemorrhage at the site of reaction
      regularly in those infected with B.C.G. and frequently in those infected with a
      virulent strain. 6. Filtrates from B. coli, B. typhosus, or meningococci injected
      into the skin of tuberculous guinea pigs do not produce visible inflammation.
      When these injections are followed by intravascular injections of the same
      material hemorrhages do not occur in the skin. 7. When concentrated broth or
      turpentine is introduced into the skin of tuberculous guinea pigs and later
      typhoid filtrate is injected into the vascular system, hemorrhages do not occur
      in the skin at the site of inflammation. 8. The majority of guinea pigs that
      receive an intravascular injection of typhoid filtrate react with hemorrhage at
      the site of the injection of the silver nitrate. The incidence of hemorrhagic
      reaction in tuberculous guinea pigs is higher than in non-tuberculous guinea pigs
      that received similar injections of silver nitrate and typhoid toxin. 9. In
      tuberculous guinea pigs the skin can be prepared for the hemorrhagic reaction not
      only by bacterial toxins but also by tuberculin, horse serum, and an inorganic
      chemical, silver nitrate. 10. In the guinea pig the skin preparatory agents, i.e.
      tuberculin in the tuberculous guinea pig, diphtheria toxin and silver nitrate in
      both tuberculous and non-tuberculous guinea pigs, tend to produce hemorrhages in
      the skin even without subsequent injection of a toxic bacterial product. This
      property of the skin preparatory agents may be essential in their action. 11.
      Hemorrhages occur in the skin at the site of tuberculin reaction not only after
      the intravascular injection of bacterial toxins or tuberculin, but also after the
      injection of substances of non-bacterial origin; namely, peptone or soluble
      starch.

PMID- 19870332
TI  - COMPARISON OF THE HEMACYTOLOGICAL CONSTITUTION OF MALE AND FEMALE RABBITS.
AB  - 1. The blood cytology of 41 pairs of virgin rabbits was studied, each pair
      consisting of a buck and a litter mate sister. A comparison of the values for
      each blood factor of the two groups was made by obtaining the mean difference and
      the standard error of the mean difference. In addition, correlation coefficients,
      both zero order and first order eliminating age, and regression equations were
      calculated for each of the blood cell elements of the bucks and does. 2. It was
      found that the male values for both the red cell count and the hemoglobin content
      were higher than the corresponding female values, and these differences were of
      statistical significance. No differences were observed between the two groups
      with respect to other cells. Significant positive correlations were obtained
      between the two sexes for the following blood constituents: Red blood cell count,
      white blood cell count, hemoglobin content, lymphocytes in both absolute and
      relative numbers, and neutrophils, basophils, and monocytes in relative numbers.
      3. Since all known variables had been held constant, it was concluded that the
      higher red cell count and hemoglobin value for the male group were the results of
      constitutional differences between the sexes. Moreover, the significant
      correlations between the blood cells of male and female litter mates were
      ascribed to hereditary influences, and thus the female as well as the male rabbit
      is available for studies on the mechanism involved in the inheritance of the
      blood formula. In addition, since high correlations were obtained for cells which
      have been found to be the most reliable indices of the natural immunity of the
      male host to subsequent inoculation with tumor or syphilis, it was concluded that
      these cells should give dependable information concerning the natural resistance
      of the female host to these two diseases.

PMID- 19870333
TI  - A VIRUS-INDUCED MAMMALIAN GROWTH WITH THE CHARACTERS OF A TUMOR (THE SHOPE RABBIT
      PAPILLOMA) : I. THE GROWTH ON IMPLANTATION WITHIN FAVORABLE HOSTS.
AB  - Rabbit papillomas developing on the skin as the result of virus inoculation can
      be readily transferred to the inner organs of favorable hosts by implanting bits
      of the living tissue. The growths thus produced proliferate actively as a rule
      and frequently cause death. Often they are markedly invasive and destructive; and
      they tend to recur after excision. Bacterial infection may greatly enhance their
      malignancy. Accidental dissemination may occur during operation, and distribution
      to the peritoneal surface has been repeatedly noted. There may be no cellular
      reaction whatever about the invading epithelium of interior growths, but usually
      some new formation of connective tissue takes place, its amount varying inversely
      with the rate of epithelial proliferation. An immediate reason exists for the
      inflammatory changes and scarring found beneath long-established skin papillomas,
      in the trauma and secondary infection to which the projecting, necrotizing masses
      have been subjected. In animals dying of progressively enlarging interior growths
      the skin papilloma may long have been stationary in size. The growths appearing
      after the transfer of papillomatous tissue to the inner organs are due to the
      survival and multiplication of transplanted cells. However, the virus can be
      readily recovered from them, in the case of wild rabbits. No distinctive changes
      in the blood of the host have been found. The virus itself is highly specific for
      the epithelium of the skin, failing to act not only upon that of the other organs
      thus far tested but even upon embryonic skin. The papilloma frequently penetrates
      into the blood and lymph vessels, especially at the edge of implantation growths.
      The intravascular injection of fragments of it sometimes results in pulmonary
      nodules of characteristic morphology. These are due to survival and proliferation
      of the injected cells. Secondary nodules have been encountered at autopsy in a
      lymph gland and in the lungs, but under conditions more suggestive of operative
      dissemination of the growth than of true metastasis. Implantation growths of the
      papilloma in favorable hosts have the morphology of epidermoid tumors of greater
      or less malignancy. They behave as these do and elicit similar changes in the
      surrounding tissue. The attributes and potentialities of the papilloma will be
      further considered in Papers II and III.

PMID- 19870334
TI  - A VIRUS-INDUCED MAMMALIAN GROWTH WITH THE CHARACTERS OF A TUMOR (THE SHOPE RABBIT
      PAPILLOMA) : II. EXPERIMENTAL ALTERATIONS OF THE GROWTH ON THE SKIN:
      MORPHOLOGICAL CONSIDERATIONS: THE PHENOMENA OF RETROGRESSION.
AB  - The injection of Scharlach R into the skin about rabbit papillomas resulting from
      virus inoculation causes them to invade the underlying tissue and form large,
      fleshy masses beneath the surface. Histologically these appear malignant, and
      they frequently invade the blood vessels. Covering young papillomas with a layer
      of collodion causes them to burrow downwards with result in discoid masses which
      enlarge progressively, both by expansive growth beneath the epidermis and by
      invasion. Such masses, like the nodules resulting from implantation, have the
      papillae turned toward their interior, the apparent reverse of the condition of
      affairs when the growth is situated on the skin surface. The reasons for this are
      analyzed. The peculiarities of the host influence skin papillomas not a little,
      as is plain from the forms they assume; but the epithelial changes induced by the
      virus take a single direction, and no significant variations from type have been
      encountered. Local or generalized retrogression of the experimentally induced
      papilloma is not uncommon. The histological alterations that take place are
      identical with those attending retrogression of the epidermoid tumors, and the
      reactive changes taking place in the surrounding tissue are also like those about
      such tumors. The slowing and cessation of growth that occur secondarily in the
      case of virus-induced skin papillomas are associated with the formation under
      them of a dense layer of connective tissue, and to this their behavior is
      attributable. Similar findings have been often recorded for tumors, notably for
      the epidermoid cancers produced in rabbits by tarring.

PMID- 19870335
TI  - A VIRUS-INDUCED MAMMALIAN GROWTH WITH THE CHARACTERS OF A TUMOR (THE SHOPE RABBIT
      PAPILLOMA) : III. FURTHER CHARACTERS OF THE GROWTH: GENERAL DISCUSSION.
AB  - Experimental study of the rabbit papilloma of Shope, a growth caused by a virus,
      has shown that it possesses the immediate characters whereby tumors are
      recognized. Often it looks and acts like a malignant neoplasm. It differs from
      the tumors as a group, however, in its incidence which is that of an infectious
      process, and from other mammalian tumors in that its cause has been demonstrated.
      The possible bearing of the findings upon the problem of tumor causation is
      discussed. The morphology and behavior of the generality of tumors can no longer
      be taken to exclude the possibility that these are produced by extraneous, living
      entities. The incidence of some of the tumors at least, and the failure to
      demonstrate their cause can both be explained on the assumption that they are due
      to such entities, widely distributed in or upon the animal population but
      effective only under special circumstances. Present knowledge makes this
      assumption reasonable as a basis for further work.

PMID- 19870336
TI  - ULTRAFILTRATION OF THE VIRUS OF POLIOMYELITIS.
AB  - From the ultrafiltration analysis the size of the virus of human poliomyelitis
      has been estimated to be somewhere between 12 and 17 mmicro. Technical
      difficulties encountered and the low concentration of the virus make it seem
      possible that the virus is even smaller.

PMID- 19870337
TI  - THE PROBLEM OF THE SIGNIFICANCE OF THE INCLUSION BODIES FOUND IN THE SALIVARY
      GLANDS OF INFANTS, AND THE OCCURRENCE OF INCLUSION BODIES IN THE SUBMAXILLARY
      GLANDS OF HAMSTERS, WHITE MICE, AND WILD RATS (PEIPING).
AB  - 1. Acidophilic intranuclear inclusion bodies occur in the salivary glands of
      Chinese infants dying from miscellaneous causes. The lesion is similar to that
      previously described in infants in Europe and America. 2. Attempts to prove that
      this lesion is due to an infectious agent by its production in animals have been
      unsuccessful. 3. Acidophilic intranuclear inclusion bodies have been found in the
      submaxillary glands of hamsters, white mice, and wild rats. 4. Evidence is
      presented to show that the lesion in hamsters, white mice, and wild rats is due
      to a virus, which is specific for each species, being transmissible to normal
      individuals of this breed, and which is very similar to the submaxillary gland
      virus of guinea pigs.

PMID- 19870338
TI  - THE EFFECT OF STAPHYLOCOCCUS AUREUS TOXIN ON THE KIDNEY.
AB  - 1. The hemolytic Staphylococcus aureus elaborates a toxin in vitro that when
      injected intravenously produces lesions in the kidneys of rabbits and cats. 2.
      The toxin injures primarily the blood vessels of the kidney.

PMID- 19870339
TI  - EXPERIMENTAL STUDIES ON ENCEPHALITIS : I. TRANSMISSION OF ST. LOUIS AND KANSAS
      CITY ENCEPHALITIS TO MICE.
AB  - 1. Mice of special strains injected intracerebrally with a 10 per cent emulsion
      of bacteria-free brain tissue from fatal cases of encephalitis in St. Louis and
      Kansas City develop a characteristic and fatal encephalitis. 2. Transmission of
      the disease can be continued indefinitely by injecting the bacteria-free brain
      tissue from the infected mice into healthy mice. 3. In the injected mice there is
      a 3 to 4 day incubation period, followed by hyperesthesia, coarse tremors,
      convulsions, prostration, and death in from 4 to 6 days. 4. The lesions in the
      mice with experimental encephalitis consist chiefly of perivascular accumulations
      of mononuclear leucocytes throughout the brain, stem, cord, and the pia, and
      destruction of pyramidal cells in the lobus piriformis and cornu Ammonis. 5. The
      human encephalitis brain tissue preserved in glycerine from the time of death of
      the patient apparently loses its infectivity for mice in about 32 days.

PMID- 19870340
TI  - I. BARTONELLA INCIDENCE IN SPLENECTOMIZED BILE FISTULA DOGS.
AB  - Splenectomized bile fistula dogs in this laboratory have regularly exhibited
      spontaneous periods of anemia, which are associated with excessive bile pigment
      production. In three out of four dogs, such periods have been shown to be
      associated with the presence in the blood of bodies morphologically
      indistinguishable from descriptions of Bartonella canis. Simple splenectomized
      dogs have not shown such periods of anemia arising spontaneously. Inoculations of
      blood containing Bartonella bodies into two splenectomized dogs have resulted in
      intervals of blood destruction associated with the presence in their blood of
      bodies similar to those in the inoculated blood. Injection of such blood into a
      splenectomized biliary-renal fistula dog has resulted in a similar picture.
      Efforts to cultivate Bartonella bodies in artificial culture media have so far
      been unsuccessful. Neosalvarsan appears to have a specific sterilizing effect on
      the condition. Spleen extract feeding appears to have an inhibiting effect upon
      the periods of anemia and bile pigment overproduction.

PMID- 19870341
TI  - II. HEMOGLOBIN AND BILE PIGMENT OVERPRODUCTION IN THE SPLENECTOMIZED BILE FISTULA
      DOG.
AB  - Blood destruction associated with Bartonella or with a drug (hydrazine) in bile
      fistula dogs yields a large pigment excess. These dogs form large amounts of new
      hemoglobin and bile pigment on a diet which permits of but little new hemoglobin
      production in standard anemic dogs. When hemoglobin formation and hemoglobin
      destruction are occurring rapidly and simultaneously, estimations of the
      percentage of circulating hemoglobin alone, though showing the eventual total
      increase or decrease of this substance, do not permit one to determine the actual
      amounts formed or destroyed. It is suggested that the body can produce readily a
      large amount of the pyrrol aggregate (four pyrrol rings) which may go to form new
      hemoglobin. At the same time the globin is probably saved from destroyed red
      cells and turned over into new hemoglobin for new red cells. It is certain that
      globin may be a determining factor under certain circumstances in the
      construction of new hemoglobin for new red cells. Our knowledge about the
      construction and internal metabolism of globin is extraordinarily limited.

PMID- 19870342
TI  - THE ASSOCIATION OF BARTONELLA BODIES WITH INDUCED ANEMIA IN THE DOG.
AB  - On feeding to splenectomized dogs a diet producing black tongue, severe anemia
      developed associated with the presence of small bodies in or on the erythrocytes.
      The bodies were morphologically similar to Bartonella muris and Bartonella canis.
      The addition of lean beef to the diet, a material prophylactic against its
      effects, was followed by improvement of the blood levels, the presence of
      increased numbers of reticulocytes in the circulating blood, and the
      disappearance of the bodies. When the blood containing Bartonella-like bodies was
      injected into other splenectomized dogs fed a normal or a black tongue-producing
      diet, anemia developed in them and the bodies appeared in large numbers. Similar
      injections into non-splenectomized animals fed in the same way had anemia alone
      as its result. Injections into normal animals fed a normal diet caused not even
      anemia.

PMID- 19870343
TI  - ON THE PRESERVATION OF TYPHUS FEVER RICKETTSIAE IN CULTURES.
AB  - 1. Cultures of typhus fever rickettsiae were as a rule found to remain viable and
      virulent after being stored at 37 degrees and -20 degrees C. for several months,
      whereas they failed to survive when stored at the intermediate temperatures of 20
      degrees and -4 degrees C. for 4 weeks and 10 days respectively. In one instance
      cultures were stored at 37 degrees C. for 8 months without having been
      transferred, and were subsequently found to be viable and infectious. 2. The
      conditions influencing such long survival of an organism which seems to require
      living tissue for multiplication (as filterable viruses do in general) are
      discussed. 3. Typhus-infected tissues (minced guinea pig tunica) suspended in a
      serum-Tyrode mixture in sealed flasks remained infectious at 37 degrees C. for at
      least 10 weeks. 4. Additional evidence for the etiological significance of the
      rickettsiae in typhus fever is obtained from the experiments described.

PMID- 19870344
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : X. CHEMICAL PROPERTIES OF
      CHICKEN TUMOR EXTRACTS.
AB  - A brief description is given of the main physical and chemical characteristics of
      active chicken tumor extracts. By special methods constituents have been removed
      from the active solution: (1) the major part of the tumor-proteins, which are
      adsorbed on alumina gel and discarded; (2) a carbohydrate, present in large
      amounts in the tumor extract, is eliminated by precipitation in combination with
      gelatin. In both cases the tumor principle is not directly affected and largely
      remains in active form in the solution.

PMID- 19870345
TI  - PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR : XI. CHEMICAL COMPOSITION
      OF PURIFIED CHICKEN TUMOR EXTRACTS CONTAINING THE ACTIVE PRINCIPLE.
AB  - The fractionation of active chicken tumor extracts has been continued. 1. By a
      rapid method of dialysis the diffusible fraction of the treated extract,
      representing about 75 per cent of the solids, has been eliminated without
      reducing the tumor-producing activity. 2. Combined methods of fractionation have
      resulted in the elimination of as much as 95 per cent of the total solids of the
      extract as inactive constituents. Since there was some concomitant enhancement of
      the activity of the agent the results were equivalent to a 25-fold concentration
      of it in terms of dry weight. 3. The chemical content of the undiffusible
      fraction has been determined in terms of total nitrogen, reducing substances,
      sulfur, phosphorus, and lipoids. 4. The evidence points to a protein and a
      phospholipoid as the principal constituents of the active residue. Further
      fractionation is being attempted with a view to connecting the tumor-producing
      activity with one of its remaining constituents.

PMID- 19870346
TI  - THE DEMONSTRATION OF A TUMOR GROWTH-INHIBITING FACTOR FROM NORMAL HUMAN
      CONNECTIVE TISSUE.
AB  - Extracts from fresh normal human connective tissue (rectus sheath) exhibited a
      decided inhibiting action on grafts of Rat Tumor 256 transplanted into test
      animals. There was complete inhibition of tumor growth in 66 per cent of the
      animals; there was a marked retardation in the rate of growth in another 15 per
      cent, the tumors in these instances being much smaller than the controls
      transplanted at the same time. In only one experiment was there failure to obtain
      a lasting growth-inhibitory effect. The tumors in these animals (19 per cent)
      although showing an initial retardation in growth, apparently overcame the
      restraint and at the end of 5 weeks were larger than the control series. Extracts
      from fresh normal human muscle tissue, on the other hand, showed no such
      inhibiting action on grafts of Rat Tumor 256.

PMID- 19870347
TI  - PRESSOR SUBSTANCES FROM THE BODY FLUIDS OF MAN IN HEALTH AND DISEASE.
AB  - 1. Extracts of human blood plasma, ascitic and cerebrospinal fluids have been
      shown to contain a substance or substances which have a prolonged and powerful
      pressor action when injected into test animals. 2. The chemical properties of the
      substance suggest those of an organic base. It is extracted with alcohol, soluble
      in water and acetone, extracted from water by chloroform, and probably is but
      slightly heat-stable. The plasma colloids seem to hold the substance in a bound
      state since it does not appear in the ultrafiltrate and is liberated on
      coagulation of the colloids by alcohol. Coagulation alone of the blood does not
      cause the substance to be formed. 3. Its action suggests that its pressor effect
      is brought about by mediation of the central nervous system. This inference was
      drawn from the following observations. (a) The functional intactness of the
      central nervous system is essential in order that pressor responses be obtained.
      Unanesthetized animals exhibit greater vascular responses than do anesthetized.
      (b) Pithing animals completely abolishes the response. Progressive ablation of
      the brain to the level of the hind brain does not alter the response, but below
      this level, injury abolishes the activity of the extract. (c) Some substance in
      the extract sensitizes the mechanism responsible for the carotid sinus reflex.
      (d) There is no parallelism between the response to peripherally acting drugs and
      pressor extracts. (e) Removal of the adrenal glands does not affect its
      character. 4. The rise in blood pressure appears to be due especially to
      constriction of the arteries in the splanchnic region. 5. Assay of the pressor
      extracts is made difficult because of the dependence of the vascular response on
      the functional state of the central nervous system. The carotid sinus reflex and
      stimulation with carbon dioxide-air mixtures have proved most useful means for
      the estimation of this functional state. It has been pointed out that the
      vascular responses to extract, stimulation of the carotid sinus, and inhalation
      of carbon dioxide-air vary greatly during the course of an experiment on
      anesthetized animals. This natural history of the vascular responses has been
      described. 6. No evidence has been produced by the method employed that the
      amount of this pressor substance is increased in the blood or spinal fluid of
      patients with hypertension of varied pathogenesis (nephritic hypertension,
      essential hypertension, malignant hypertension, eclampsia, and pituitary
      basophilism).

PMID- 19870348
TI  - CORTIN PROTECTION AGAINST ANAPHYLACTIC SHOCK IN GUINEA PIGS.
AB  - Studies have been made on a possible protective action of cortin in the
      prevention of anaphylactic shock induced by crystallized egg albumin. Of sixteen
      control guinea pigs only two survived. Sixteen of thirty-three cortin-treated
      animals received hormone at the optimum period of from 2 to 6 hours before the
      shocking dose. Nine survived and two others showed some protection. In groups
      treated at other time intervals the evidence of protection is inconclusive. 2
      weeks after the first test the cortin-treated survivors succumbed to a second
      antigen dose, which was not preceded by cortical extract.

PMID- 19870349
TI  - OBSERVATIONS ON THE DEPRESSOR EXTRACTS OF HUMAN BLOOD AND ON THE VASCULAR ACTION
      OF EXTRACTS OF RABBIT AND DOG BLOOD.
AB  - 1. Alcoholic extracts of the plasma of rabbits obtained from arterial or venous
      blood differ from those of human plasma in having a marked depressor action on
      the blood pressure of anesthetized cats. This action is unantagonized on
      atropinization. Extracts of the plasma of dogs, on the other hand, are almost
      without vascular effect. 2. Ultrafiltrates of the plasma of rabbits are actively
      vasodepressor, while those of human and dog plasma are without action. 3.
      Extracts of the plasma of rabbits reduce the renal volume greatly and they have a
      relatively weak dilator action on the arteries of the periphery. These effects
      resemble those of adenylic acid more than those of histamine. 4. It is possible
      that the pressor-depressor substances of the blood are species-specific. 5. Human
      plasma, ascitic and spinal fluid which have been allowed to stand, yield extracts
      that are depressor and in their pharmacological action resemble closely extracts
      prepared from red blood cells and acetic acid extracts of tissues. Their
      constrictor effect on the kidneys is marked. 6. Histamine, choline, and adenosine
      depress the level of the blood pressure more effectively than they constrict the
      volume of the kidneys, while the reverse is true when adenylic acid is employed.

PMID- 19870350
TI  - STUDIES ON ANAPHYLAXIS WITH POLLEN.
AB  - 1. Guinea pigs injected intracutaneously and subcutaneously with extract of the
      pollen of burweed marsh-elder in relatively small amounts did not show
      anaphylactic response to intravenous shock doses of this material 3 weeks later.
      2. If, however, the animals were sensitized with horse serum either before, or
      along with the same pollen injections, they could then be shocked after an
      interval of 3 weeks with pollen extract alone. 3. The possible role of this
      underlying sensitivity is discussed.

PMID- 19870351
TI  - SALT AND WATER LOSSES IN DIURETIN DIURESIS AND THEIR RELATION TO SERUM NON
      PROTEIN NITROGEN AND ELECTROLYTE CONCENTRATIONS.
AB  - The losses of sodium, potassium, chloride, nitrogen, and water following the
      administration of diuretin to rabbits over 5 to 9 day periods together with the
      changes in serum concentrations of sodium, chloride, N. P. N., and total protein
      occurring simultaneously with these losses are described. The circumstances
      responsible for the presence of azotemia in the animals were investigated in
      particular and the dependence of nitrogen retention upon dehydration and the
      modification of this dependence by variation in urine volume were demonstrated.
      It was clearly shown that no direct relationship exists between the azotemia and
      the coincident hypochloremia. It was found that nitrogen retention can be removed
      by the administration of water without salt, and the extent to which serum
      electrolyte and protein concentrations can be lowered by this procedure was also
      observed. The withdrawal from the body of large amounts of potassium as well as
      of sodium and chloride following the administration of diuretin, and also the
      inefficacy of sodium chloride solution in preventing the potassium loss was
      demonstrated.

PMID- 19870352
TI  - THE EXPERIMENTAL PRODUCTION IN DOGS OF ACUTE STOMATITIS, ASSOCIATED WITH
      LEUCOPENIA AND A MATURATION DEFECT OF THE MYELOID ELEMENTS OF THE BONE MARROW.
AB  - An ulcerative stomatitis associated with leucopenia and granulopenia can be
      induced in dogs by means of a diet causing black tongue. The decrease of
      circulating leucocytes is due to a suppression of maturation of the
      erythropoietic elements of the bone marrow. The changes as a whole have a
      resemblance to those occurring in human beings with acute agranulocytosis.

PMID- 19870353
TI  - FURTHER STUDIES ON KALA-AZAR : LEISHMANIA IN NASAL AND ORAL SECRETIONS OF
      PATIENTS AND THE BEARING OF THIS FINDING ON THE TRANSMISSION OF THE DISEASE.
AB  - THE SUMMARY OF OUR EXPERIMENTS (TABLE V) INCLUDING DATA PREVIOUSLY REPORTED IS AS
      FOLLOWS: 1. Twenty-two patients were studied, in all of whom the diagnosis of
      kala-azar was confirmed by puncture of the spleen or liver, with recovery of
      Leishman-Donovan bodies. 2. Microscopic examination of the nasal secretions
      revealed typical parasites in twelve (54.5 per cent) of the twenty-two cases. 3.
      Microscopic examination of smears from the pharyngeal tonsils of ten patients
      showed parasites in three (30 per cent). 4. The results of intraperitoneal
      inoculation into hamsters of nasal discharge from fourteen patients proved that
      the parasites were present and had retained their infectivity in thirteen (92.8
      per cent). 5. Intraperitoneal inoculation into animals of sputum or saliva killed
      many animals before sufficient time had elapsed for the presence or absence of
      infection with leishmania to be demonstrated. However, in eight cases animals
      survived and in two of these (25 per cent) transmission of the disease had
      occurred. 6. Material obtained from the pharyngeal tonsils of two patients, when
      inoculated intraperitoneally into hamsters resulted in infection with leishmania
      in both instances. 7. Single inoculations, into the oral and nasal cavities of
      hamsters, of nasal discharge from five patients have resulted in transmission of
      leishmaniasis in one instance only, but these experiments are incomplete. 8.
      Repeated inoculations by the oral and nasal routes of hamsters and of two human
      volunteers with nasal secretions from patients with kala-azar have not yet been
      concluded, but to the present date have resulted negatively. 9. Emulsions of
      material from the pharyngeal tonsil of one patient, when fed to three hamsters in
      amounts of from 0.1 to 0.2 cc. on one occasion only, resulted in generalized
      infection with leishmania in each of the animals. 10. Evidence as obtained from
      the medical literature both for and against the transmission of kala-azar by
      direct or indirect contact and by means of the bite of the sand-fly is presented.

PMID- 19870354
TI  - DIAGNOSIS OF PSITTACOSIS IN MAN BY MEANS OF INJECTIONS OF SPUTUM INTO WHITE MICE.
AB  - By means of intraperitoneal injections in mice of unfiltered sputum or filtrates
      of sputum a large percentage of the cases of psittacosis in human beings can be
      successfully diagnosed in a relatively safe manner.

PMID- 19870355
TI  - A STUDY OF REPEATED ATTACKS OF EXPERIMENTAL PNEUMOCOCCUS LOBAR PNEUMONIA IN DOGS.
AB  - A study has been made of repeated attacks of experimental lobar pneumonia in the
      dog produced by the intrabronchial injection of Pneumococcus Type I. Twenty-five
      individual dogs were given 78 infections in all at intervals of 3 days to 19
      months. The number of attacks to which a single animal was subjected varied from
      two to eleven. It was found that recovery from this experimental disease
      conferred on the animal increased resistance against subsequent infections as
      shown by the fact that such animals regularly survived doses of culture which in
      the dog infected for the first time produced a fatal outcome. The recurrent
      attacks of pneumonia were uniformly mild in character; the febrile course was
      brief; the pulmonary lesion was usually confined to a single lobe, and bacteremia
      seldom occurred. There was no detectable difference between the second and the
      subsequent infections, which could be produced whenever desired, nor did the time
      intervals between attacks appear to bear any relationship to the severity of the
      experimental disease. Tests for acquired antipneumococcal immune substances in
      the blood after recovery showed their presence in some animals and not in others,
      yet dogs without demonstrable humoral immunity appeared to be just as resistant
      to reinfection as those possessing it. A comparison of the pathogenesis of these
      secondarily induced lesions with those of the initial infection revealed certain
      striking differences between the two. Secondary lesions produced in the lobe
      previously affected tended to evolve much more rapidly than did the primary ones.
      They were characterized by the early appearance of a generalized macrophage
      reaction and a marked diminution in the numbers of pneumococci in the tissues or
      their complete absence. These changes occurred more slowly in secondary lesions
      initiated in hitherto uninvolved lobes. The macrophage reaction, which consists
      of a swelling of the fixed tissue cells (histiocytes) and a subsequent liberation
      of macrophages into the alveolar exudate, is regarded as a significant evidence
      of increased antipneumococcal resistance, since it has been observed to occur
      regularly at the time of recovery from the first infection and is accompanied by
      the local disappearance of the invading microorganisms.

PMID- 19870356
TI  - TESTS FOR PNEUMOCOCCUS HYPERSENSITIVENESS IN DOGS AFTER RECOVERY FROM
      EXPERIMENTAL PNEUMOCOCCUS LOBAR PNEUMONIA.
AB  - The data derived from the above described investigations indicate that dogs do
      not develop hypersensitivity to the pneumococcus as the result of experimental
      lobar pneumonia. This inference is based on the following findings: 1. Fifteen
      dogs were given Type I and Type II pneumococcus lobar pneumonia and following
      recovery were tested for hypersensitiveness by means of intrabronchial and
      intracutaneous injections of the autolysate made from the homologous
      pneumococcus. 2. Seven dogs showed a pulmonary lesion discernible with the X-ray
      at site of the autolysate inoculation; three of these dogs were normal controls.
      3. No evidence of a positive skin reaction was found in any of the fifteen dogs,
      many of which received repeated infections and intradermal autolysate injections.
      4. Subsequent infections in the same animals were definitely milder than the
      initial infection. 5. The infections following the administration of
      intrapulmonary and cutaneous autolysate were practically of the same intensity as
      the initial infection. 6. Temperature, pulse rates, white blood counts and
      differential blood pictures showed no significant variations following
      intrapulmonary injection of autolysate. 7. Tests for the acquisition of humoral
      immune bodies following autolysate injection and recovery from the experimental
      disease showed the presence of these substances in some of the dogs and their
      absence in others. 8. Study of the pathology of the pulmonary lesions produced by
      the autolysate failed to reveal histological changes characteristic of an
      allergic reaction. However, the presence of perivascular accumulations of large
      mononuclear cells observed in the lesions of the recovered dogs does suggest a
      locally accelerated reactivity of the fixed tissue cells to the products of the
      pneumococcus.

PMID- 19870357
TI  - THE DEVELOPMENT OF PURE CULTURES OF FIBROBLASTS FROM SINGLE MONONUCLEAR CELLS.
AB  - 1. Most isolated guinea pig mononuclear exudative cells in tissue culture become
      typical migrating macrophages, but a small proportion take on fibroblastic
      characteristics, and produce pure colonies of fibroblasts. These fibroblasts
      maintain their morphological characteristics through repeated subcultures. 2. It
      is suggested that the subsequent development of individual mononuclear cells in
      tissue culture is conditioned at the time of explantation. 3. Apposition with
      other cells is not necessary for the initiation of mitotic cellular division. 4.
      There is a definite optimal relationship between the bulk of the medium, the
      number of explanted cells and the extent of proliferation. The presence of other
      cells in the vicinity enhances cellular division. 5. Mitosis in the isolated
      explanted cell is preceded by a latent period. The rate of division varies in
      different colonies of fibroblasts. 6. Admixed erythrocytes in the mononuclear
      suspension definitely inhibit proliferation of fibroblasts in tissue culture. The
      inhibiting factor in disintegrating erythrocytes is apparently present in the
      stroma.

PMID- 19870358
TI  - BLOOD PLASMA PROTEIN REGENERATION CONTROLLED BY DIET : SYSTEMATIC STANDARDIZATION
      OF FOOD PROTEINS FOR POTENCY IN PROTEIN REGENERATION. FASTING AND IRON FEEDING.
AB  - When blood plasma proteins are depleted by bleeding, with return of washed red
      cells (plasmapheresis) it is possible to bring the dog to a steady state of low
      plasma protein and uniform plasma protein production on a basal diet. Such dogs
      are excellent test subjects by which the potency of various diet factors for
      plasma protein regeneration can be measured. To regenerate plasma proteins in any
      significant amount the depleted dog requires food protein. Some proteins are very
      potent for new plasma protein production and others are utilized poorly. Beef
      serum is very potent and its proteins (2.6 gm.) will produce 1 gm. of new plasma
      protein in the depleted dog-a potency ratio of 2.6. Kidney protein stands at the
      bottom of our list and the dog needs 21 gm. of kidney protein to regenerate 1 gm.
      of plasma protein-a potency ratio of 21.0. Some grain proteins approximate the
      potency of beef serum and may show potency ratios of 2.7 to 4.6. Some of these
      grain proteins appear to favor the production of globulin more than albumin in
      the plasma. Skeletal muscle, gizzard (smooth muscle), lactalbumin and egg white
      fall into a favorable group with a potency ratio of 5.3 to 6.0. Whole liver,
      liver fractions, casein, and beef heart are a little less potent and present
      potency ratios of 6.5 to 8.0. Many of these food substances favor the production
      of albumin more than globulin. Pancreas and salmon muscle show less favorable
      potency ratios of 19.0 and 15.0 respectively. Fasting periods indicate that these
      depleted dogs can produce little if any new plasma protein. Iron feeding in some
      unexplained manner will influence body metabolism so that an excess of plasma
      protein will be produced. These observations have a bearing on clinical
      conditions associated with hypoproteinemia and give suggestions for diet aid or
      control in some of these abnormal states. The make-up of the diet is obviously of
      great interest and it is possible that protein combinations may be more potent
      than a single protein or that food potency ratios may differ in health and
      disease.

PMID- 19870359
TI  - DOG PLASMA PROTEIN GIVEN BY VEIN UTILIZED IN BODY METABOLISM OF DOG : HORSE
      PLASMA AND DOG HEMOGLOBIN NOT SIMILARLY UTILIZED.
AB  - Foreign plasma protein (horse) introduced parenterally into the protein fasting
      dog is not utilized in the body economy. Its fate appears to be disintegration
      and elimination as excess urinary nitrogen. This is totally different from the
      fate of dog plasma protein under similar conditions. Dog hemoglobin given
      parenterally to the protein fasting dog is not utilized as is dog plasma protein
      to keep the animal in nitrogen equilibrium but the globin is largely broken down
      and discarded as excess urinary nitrogen. A small part of the injected hemoglobin
      is probably utilized to maintain the red cell concentration in the blood at high
      levels. Dog plasma given parenterally in a protein fasting dog will maintain the
      dog in nitrogen equilibrium and there is no surplus nitrogen elimination in the
      after periods. It is apparent that the introduced plasma protein is utilized
      efficiently in body metabolism to replace or repair tissue protein. It is
      suggested that although this is an emergency reaction the same reactions may go
      on in normal internal metabolism. The observation that foreign plasma and dog
      hemoglobin cannot be utilized when given parenterally actually strengthens this
      last argument for a normal contribution from plasma proteins to body proteins.

PMID- 19870360
TI  - NUTRITIONAL EDEMA IN THE DOG : I. DEVELOPMENT OF HYPOPROTEINEMIA ON A DIET
      DEFICIENT IN PROTEIN.
AB  - 1. The concentration of protein in the serum and plasma of normal dogs is given.
      Analyses of serum from 38 animals yielded the following averages and standard
      deviations, (a) for albumin: 3.26 +/- 0.48 gm. per cent, (b) for globulin: 2.72
      +/- 0.76 gm. per cent, and (c) for total protein: 5.98 +/- 0.67 gm. per cent.
      Analyses of plasma from 19 animals showed, (a) for albumin: 3.38 +/- 0.38 gm. per
      cent, (b) for globulin: 2.98 +/- 0.55 gm. per cent, and (c) for total protein:
      6.36 +/- 0.71 gm. per cent. 2. A diet for dogs is described, the feeding of which
      results in a progressive decline in the concentration of protein in the serum. A
      composite curve constructed from the findings with 21 animals discloses a rapid
      initial fall and a slower subsequent decrease in albumin and total protein and an
      approximately constant level for globulin. The course of the globulin curve was
      subject to wide variation in separate experiments, both increases and decreases
      being recorded. 3. With five dogs the nitrogen balance was followed through a
      total of 42 metabolism periods of approximately 7 days each. The average daily
      loss of nitrogen was 1.15 gm. Approximate calculations disclose that only 3 or 4
      per cent of the nitrogen eliminated is accounted for by the decline in
      circulating protein, the remainder being represented by loss from the tissues. 4.
      An episode is described with one dog when, during a period of self-imposed
      fasting, the serum albumin regenerated to a normal level, apparently at the
      expense of catabolized tissue protein. 5. The course of serum proteins is
      described during the recovery which follows interruption of the low protein diet
      and return to a regime of adequate feeding. 6. A discussion is given of the
      relationship between tissue proteins and plasma proteins. The data permit one to
      entertain the hope that a way will be found for stimulating an internal
      readjustment to provide temporary relief from hypoproteinemia, a way which will
      depend upon the potential ability of the tissues to provide sufficient protein
      for the needs of the plasma.

PMID- 19870361
TI  - RENAL DAMAGE FOLLOWING THE INGESTION OF A DIET CONTAINING AN EXCESS OF INORGANIC
      PHOSPHATE.
AB  - The addition of an excess of inorganic phosphate in the form of orthophosphoric
      acid, acid, basic or neutral sodium or potassium phosphate to the diet of albino
      rats results in the development of an interesting and permanent renal lesion. The
      phosphate renal lesion is characterized by a necrosis of the cells of the
      convoluted tubules commencing at the terminal end, followed by a regeneration of
      atypical epithelium and calcification of the necrotic debris that fills the
      tubules. The entire outer stripe of the outer zone of the medulla is transformed
      into a zone of distorted structures and there is an increase in the interstitial
      connective tissue. The adjoining cortex is also involved with cystic dilatation
      of tubules and collapse. Such areas may reach the free surface of the organ and
      produce a retracted scar. In the gross the kidneys are enlarged and firm on
      section with a pebbled surface produced by numerous scars. The maximum changes in
      the kidney structure are reached after some 15 days although necrosis of the
      convoluted tubule cells is evident after a single day of phosphate feeding. The
      renal structure is not restored to its normal form when the excess of phosphate
      is removed from the diet.

PMID- 19870362
TI  - THE SEROLOGICAL DIFFERENTIATION OF PATHOGENIC AND NON-PATHOGENIC STRAINS OF
      HEMOLYTIC STREPTOCOCCI FROM PARTURIENT WOMEN.
AB  - 1. The majority of strains of hemolytic streptococci from puerperal infections of
      the uterus were identified serologically as members of the Group A described by
      Lancefield. 2. The majority of strains isolated from the birth canal of women
      whose puerperium was afebrile were not members of Group A. 3. The existence of
      two new serological groups of hemolytic streptococci, Groups F and G, is
      described.

PMID- 19870363
TI  - STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL : III. THE EFFECT OF
      EXTRANASAL INJECTION ON THE GROWTH OF THE FOWL CORYZA BACILLUS.
AB  - The mucous surfaces of the nasal passages and orbital sinuses appear to afford
      particularly favorable conditions for the development of the fowl coryza
      bacillus. Injected in the nasal tract, in any appreciable number, the bacilli
      regularly develop and may continue to exist for a considerable period of time in
      spite of an active inflammatory reaction on the part of the host. The specific
      bacillus multiplies either sparsely or not at all when injected extranasally,
      regardless of the nature of the cellular surface with which it is brought in
      contact. If the locus of injection is in communication with the upper air
      passages, as in the case of the trachea, internal ear, and orbital cavity, the
      bacilli may be carried there, even in the absence of a local development, and
      produce a coryza. Introduction of the bacilli in loci not in communication with
      the upper air passages is followed by a nasal carriage only in the case of the
      peritoneal cavity. Following intraperitoneal injection, 7 of 12 birds showed the
      specific bacillus in the nasal passages and except in one instance without an
      accompanying inflammation.

PMID- 19870364
TI  - STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL : IV. SUSCEPTIBILITY
      AFTER EXTRANASAL INJECTION OF THE FOWL CORYZA BACILLUS.
AB  - Intratracheal, intracloacal, and subcutaneous injection of living cultures of the
      fowl coryza bacillus had no demonstrable effect on the susceptibility of fowl to
      coryza. Intraperitoneal injection was irregularly followed by a definitely
      altered susceptibility. Growth of the specific bacillus was inhibited in the
      nasal tract of approximately 70 per cent of 25 birds which had received an
      earlier intraperitoneal injection.

PMID- 19870365
TI  - PHENOMENON OF LOCAL SKIN REACTIVITY TO BACILLUS TUBERCULOSIS : I. SKIN
      PREPARATORY AND REACTING POTENCIES OF TUBERCULIN, O.T., AND BACILLUS TUBERCULOSIS
      CULTURE FILTRATES.
AB  - New toxic substances in certain tuberculin, O.T., and B. typhosus culture
      filtrates are described. These substances are capable of eliciting the
      hemorrhagic necrosis characteristic of the phenomenon of local skin reactivity
      provided heterologous bacterial filtrates of high potency are used either for the
      intradermal or the intravenous injection. The toxic substances apparently have no
      relationship to the tuberculin substances proper. The experiments with inactive
      preparations also demonstrate in rabbits a state of hypersensitiveness to
      tuberculin, O.T., and bacteria-free culture filtrates in the absence of
      tuberculous foci. The reactions are elicited provided the tissues are rendered
      vulnerable through contact with certain soluble bacterial factors capable of
      eliciting the phenomenon of local skin reactivity to bacterial filtrates, and
      provided the tuberculin or the tuberculous culture filtrates are injected
      intravenously into immunized rabbits.

PMID- 19870366
TI  - GRADING OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES.
AB  - In this paper there are described methods for grading the local skin reactivity
      induced by bacterial filtrates. The grading is accomplished by titration of the
      skin-preparatory factors; and by studies on the duration of ensuing reactivity.
      It was found that the duration of reactivity depends upon the mode of preparation
      of filtrates and the microorganisms employed. Thus, it lasts for 96 hours with
      meningococcus "agar washings" filtrates; for 72 hours with B. typhosus "agar
      washings" filtrates; it disappears within 48 hours with B. typhosus tryptic
      digest broth culture filtrate and B. typhosus "agar washings" filtrates
      previously heated in the Arnold sterilizer for 20 minutes. Comparative titrations
      of the preparations employed demonstrate that the duration of reactivity is in
      direct relationship to the reacting potency. It is also shown that the skin
      preparatory potency of the filtrates and the duration of the ensuing local
      reactivity are not modified by cellular anaphylactic sensitization (Arthus
      phenomenon) to animal proteins. The exposure of tissues to the effect of certain
      soluble bacterial factors induces a high susceptibility to humoral toxic
      principles resulting from intravascular antigen-antibody interaction.

PMID- 19870367
TI  - THE COLONY MORPHOLOGY OF TUBERCLE BACILLI : I. THE PRESENCE OF SMOOTH COLONIES IN
      STRAINS RECENTLY ISOLATED FROM SOURCES OTHER THAN SPUTUM.
AB  - 1. Smooth, round, shiny, non-granular, and non-spreading colonies have been
      observed in cultures of virulent tubercle bacilli freshly isolated from eight
      human sources other than sputum. The classification of six of these strains as of
      human type was established by inoculation into rabbits and guinea pigs. 2. The 3
      per cent NaOH or 6 per cent H(2)SO(4) frequently used in the isolation of
      tubercle bacilli are definitely unfavorable to the development of smooth
      colonies. 3. It was observed that smooth colonies are produced in greater number
      when the pH of the medium (Corper's egg yolk-glycerine) is adjusted to a point
      near to but slightly on the acid side of neutral.

PMID- 19870368
TI  - EXPERIMENTAL STUDIES ON ENCEPHALITIS : II. THE SPECIFIC VIRUS CHARACTER OF THE
      INFECTIOUS AGENT FROM CASES OF ST. LOUIS AND KANSAS CITY ENCEPHALITIS, 1933.
AB  - 1. The infectious agent from fatal cases of St. Louis and Kansas City
      encephalitis passes Seitz pads in high dilution without appreciable loss of
      infectivity and traverses collodion membranes with an average pore size of 66
      mmicro or greater. 2. It is highly infectious for mice by the intracerebral and
      intranasal routes, but practically innocuous by the subcutaneous and
      intraperitoneal routes. 3. Certain strains of mice are more susceptible than
      others. 4. The agent administered to mice intranasally causes tremors and
      convulsions after a 6 to 7 day incubation period, followed by prostration and
      death in 8 to 10 days. Lesions are demonstrable in the olfactory bulbs 3 days
      after infection, in the piriform lobe after 4 days, and in Ammon's horn after 5
      days. 5. In Macacus rhesus monkeys, the agent provokes a mild, non-fatal reaction
      and the development of specific neutralizing bodies. On passage in monkeys, the
      virus becomes progressively weaker. 6. In rabbits, guinea pigs, rats, and sheep
      the agent is apparently without effect. 7. All available strains of the agent
      proved alike in effects in animals and in immunological response. 8. The
      available data enable one to conclude that the agent is a filtrable virus
      differing from those studied heretofore.

PMID- 19870369
TI  - TRANSMISSION OF MYELOID LEUKEMIA OF MICE : ITS RELATION TO MYELOMA.
AB  - A transmissible strain of myeloid leukemia of mice is described. It can be
      readily passed from diseased to healthy mice by the transfer of tissues that
      contain live cells; but inoculation fails when the latter are not present.
      Inoculation is successful in almost every mouse whose resistance is lowered by X
      rays. It is often successful in mice related to the animal in which the
      spontaneous leukemia took its origin, and occasionally successful in mice
      unrelated to it. The systemic diffuse disease (myeloid leukemia) is produced only
      by intravenous inoculation with relatively large doses, whereas subcutaneous or
      intraperitoneal inoculation results in the formation of tumors composed of
      myelocytes with basophile granules, in other words malignant blood cells of the
      strain described. Intravenous inoculation with small doses in susceptible mice,
      or similar inoculation with larger doses in somewhat resistant mice, results in
      the formation of tumors composed of myelocytes (multiple myeloma).

PMID- 19870370
TI  - THE NEUTRALIZATION TEST IN POLIOMYELITIS : COMPARATIVE RESULTS WITH FOUR STRAINS
      OF THE VIRUS.
AB  - In experiments devised to compare the neutralizing action of normal adult human
      sera on different strains of poliomyelitis virus, and to fill in certain gaps in
      our series of neutralization tests with different strains of virus on different
      types of cases in different age groups, we have made the following observations.
      1. The difference between two human and two passage strains of the virus when
      tested by this method amounted to about 25 per cent, and there was less power in
      normal adult sera to neutralize human than passage strains of virus. 2. The
      differences between the two human strains amounted to 15 per cent, and between
      the two passage strains to 8 per cent, the last figure falling within the limits
      of the experimental error of the method. The extent to which these findings
      affect certain concepts with regard to the epidemiology of poliomyelitis based on
      passage strain neutralization experiments cannot be determined from the data
      presented in this paper, except that they more or less confirm the view
      previously derived from passage strain experiments, that 70 to 95 per cent of
      normal urban adults possess in their blood, substance which neutralizes
      poliomyelitis virus in a given amount. However, certain other indications appear
      when the present results are supplemented by those we have previously obtained
      (25). Primarily, we have found no relation between the clinical acquisition of
      poliomyelitis and the presence of substance in the serum which neutralizes a
      passage strain of poliomyelitis virus. With a passage strain the results seem
      rather to bear a closer relationship to age than to illness. With a human strain
      we have obtained results in which there is some evidence, shown only in the
      juvenile group, that acquisition of the clinical disease is accompanied by the
      appearance of antiviral properties in the blood.

PMID- 19870372
TI  - FURTHER STUDIES WITH TOXIC SERUM EXTRACTS OF HEMOLYTIC STREPTOCOCCI.
AB  - 1. The same Streptococcus hemolyticus organisms may be subjected to extraction
      six times in 2 days with untreated inactivated serum with no loss in potency of
      the later extracts when the organisms are kept frozen solid during the night
      between the extractions. 2. The serum extract toxins of hemolytic streptococci
      can be preserved without deterioration for at least 6 months if kept frozen
      solid. 3. No toxins stronger than those containing 10 units per cc. for mice have
      been prepared. Reasons for thinking that this is due to the saturation of the
      serum with the toxin at this point are given. 4. Half saturation with
      (NH(4))(2)SO(4) precipitates out practically all of the hemotoxin in a
      preparation. 5. Serum extracts were made from strains of hemolytic streptococci
      other than the Gay strain and attempts were made to correlate the virulence and
      toxin production from each strain. No such correlation could be established. 6.
      The principal pathologic finding in mice inoculated with the streptococcus serum
      extract toxin is a marked degeneration of the tubular epithelium of the kidney.

PMID- 19870371
TI  - THE EFFECT OF VARIOUS PROTEIN RATIONS ON THE SERUM PROTEIN CONCENTRATION OF THE
      RAT.
AB  - 1. The effect of various percentages of protein (casein) in the diet on the serum
      protein concentration of the rat was studied. 2. With high protein rations (50
      per cent or over) there is no drop at all of serum protein concentration, even
      though the diet is otherwise poorly balanced and inadequate as evidenced by
      weight loss. 3. With protein rations under 20 per cent the serum protein
      concentration falls promptly to a level of about 5.25-5.50 gm. per cent, where it
      is maintained regardless of whether the diet contains 1, 5, or 10 per cent of
      protein. Further depletion of the blood colloid concentration seems to meet with
      resistance on the part of the body.

PMID- 19870373
TI  - EXPERIMENTAL STUDIES ON ENCEPHALITIS : III. SURVIVAL OF ENCEPHALITIS VIRUS (ST.
      LOUIS TYPE) IN ANOPHELES QUADRIMACULATUS.
AB  - Anopheles quadrimaculatus mosquitoes, fed on mice in which encephalitis virus
      (St. Louis type) is present in the blood stream, take up and retain the virus for
      the duration of their lives. The titre of the virus in mosquitoes 4 hours after
      engorging on mice with a maximum blood stream infection represents about 10,000
      lethal mouse intracerebral doses per mosquito. This titre drops during the
      following 2 weeks to about 100 lethal doses per mosquito, but from the 3rd week
      to the death of the mosquito, usually increases to approximately the original
      level and remains there. The titre of virus in mosquitoes which have engorged on
      mouse blood containing smaller quantities of virus exhibits the same drop and
      subsequent rise to the original level. The virus-containing mosquitoes did not
      infect mice or monkeys by biting.

PMID- 19870374
TI  - PRIMARY SERUM TOXICITY AS DEMONSTRATED BY THE CHICKEN EMBRYO.
AB  - 1. The 3 day old chicken embryo removed from its shell is a suitable test object
      for the demonstration of primary serum toxicity. Addition of normal rabbit type
      sera as well as Forssman antiserum causes the vascular network to contract and
      the embryo sinks in the yolk and dies. 2. Only sera of animals of the so called
      rabbit type produce this phenomenon. Sera of the guinea pig type are ineffective.
      3. Heating to 51 degrees C. destroys the complement content of normal human serum
      as also its effectiveness to produce the vascular phenomenon. 4. Up to the
      present it has not been possible to reactivate heat-inactivated normal serum by
      the addition of complement, while inactivated Forssman antiserum can be easily
      reactivated. 5. The vascular phenomenon of the chicken embryo is produced not
      only by the addition of a mixture of Forssman antiserum and complement but also
      by separate addition of both components. 6. Guinea pig type sera, containing
      dissolved Forssman antigen, are not only ineffective but actually exert an
      inhibitory influence on effective rabbit type sera as well as on Forssman
      antiserum.

PMID- 19870375
TI  - CULTIVATION OF THE VIRUS OF GRASSERIE IN SILKWORM TISSUE CULTURES.
AB  - A medium has been developed in which certain cells from the gonads of female
      silkworms multiply and live for periods of 2 to 3 weeks. In such tissue cultures,
      strains of silkworm grasserie virus were maintained in successive passages up to
      the number of ten. The virus multiplied greatly and typical polyhedral bodies
      formed in the cells of infected cultures.

PMID- 19870376
TI  - STUDIES ON THE HEMOLYTIC STREPTOCOCCUS OF HUMAN ORIGIN : I. OBSERVATIONS ON THE
      VIRULENT, ATTENUATED, AND AVIRULENT VARIANTS.
AB  - 1. Four common variants of the hemolytic streptococcus of human origin have been
      described. These have been designated the F, M, attenuated M, and C variants. 2.
      The F and M variants only have been isolated from the blood stream in
      streptococcal infections. Only the M, however, has any primary virulence for the
      mouse. 3. Both these variants resist phagocytosis in human blood under suitable
      conditions, and this appears to be a reliable test for human virulence. 4. The
      attenuated M variant, found only in laboratory cultures, has a capsule as well
      developed as that of the virulent variants, and yet does not resist phagocytosis.
      5. The C variant has no capsule and is readily phagocyted. It appears to
      correspond to the avirulent variant in other species. 6. An attempt has been made
      to correlate these four variants with those already described in the literature.
      7. The application of these findings to the problem of virulence has been
      discussed.

PMID- 19870377
TI  - STUDIES ON THE HEMOLYTIC STREPTOCOCCUS OF HUMAN ORIGIN : II. OBSERVATIONS ON THE
      PROTECTIVE MECHANISM AGAINST THE VIRULENT VARIANTS.
AB  - 1. Anantiserum which specifically protects mice against a virulent culture (M
      variant) of the hemolytic streptococcus contains specific opsonin. Phagocytosis
      of the organisms can be observed in the peritoneum of the protected mouse. 2. An
      antiserum prepared by injecting an animal with the living M variant specifically
      opsonizes both the F and the M variant of the strain. 3. Evidence is presented
      which indicates the probable identity of the specific opsonin and the anti-M
      precipitin of Lancefield (7). Agglutination appears to be dependent upon a
      different antibody. 4. It is possible to type the hemolytic streptococci by means
      of specific opsonins, and the opsonic method has certain advantages over
      agglutination, precipitation, and mouse protection tests. It is evident from what
      little has been done that there are many types. 5. The serum of infants contains
      no opsonin for the virulent hemolytic streptococci, but the serum of adults may
      contain specific opsonins for certain strains. Inasmuch as no opsonins were
      demonstrable in two polyvalent antibacterial sera examined, the possibilities of
      therapeutic transfusion are discussed.

PMID- 19870378
TI  - STUDIES ON MENINGOCOCCUS INFECTION : VII. THE STUDY OF AN ISOLATED EPIDEMIC.
AB  - The investigation of this isolated epidemic of meningococcus meningitis at a
      C.C.C. camp gave an opportunity to examine the carrier state in contacts carrying
      what were presumably virulent epidemic strains of organisms. With the aid of
      Miller's technique for the enhancement of the demonstrable virulence of
      meningococci for mice, it proved possible to test the virulence of the carrier
      strains from Camp Rusk. These results were consistent despite the interval of
      from 3 to 4 weeks which intervened between the isolation of the strains and the
      virulence titrations. Type I strains were found to have a high virulence, while
      the virulence of Type II strains was moderately high but definitely less than
      that of the Type I, and atypical strains and strains of N. catarrhalis isolated
      from carriers showed a very low virulence. The question of the precise nature of
      the carrier state was investigated. No evidence has been obtained yet as to the
      existence of a relationship between pharyngitis, coryza or upper respiratory
      disease and the presence and degree of the carrier state. This is unlike the
      situation with regard to pneumococcus carriers. On the other hand, it has proved
      possible to demonstrate reactions within the body to the meningococci in the
      nasopharynx, consisting of the formation of agglutinins and protective antibodies
      in the blood serum. 32.3 per cent of Type I and 60 per cent of Type II carrier
      sera showed moderate or good agglutinins for homologous organisms and 80 per cent
      of Type I and 40 per cent of Type II sera showed moderate or good protective
      antibodies against virulent homologous strains. No idea could be obtained as to
      the relationship of the presence or absence and the degree of serological
      reaction and the duration of the carrier state.

PMID- 19870379
TI  - THE PRECIPITIN REACTION BETWEEN TYPE III PNEUMOCOCCUS POLYSACCHARIDE AND
      HOMOLOGOUS ANTIBODY : II. CONDITIONS FOR QUANTITATIVE PRECIPITATION OF ANTIBODY
      IN HORSE SERA.
AB  - The experiments recorded above show that in the case of antipneumococcus horse
      serum or purified antibody the arbitrary immunological procedure (37 degrees for
      2 hours, overnight in the ice box) does not permit either the establishment of a
      true equilibrium or the precipitation of the maximum amount of antibody nitrogen.
      Analyses of such horse sera for antibody content should therefore be carried out
      at 0 degrees and the determinations should be allowed to stand in the cold for at
      least 24 hours in order to insure the completion of the reaction. It is believed
      that the similarity of the nitrogen: S III ratios in the specific precipitate,
      whether obtained from whole serum or from purified antibody, and the failure of
      added serum to influence the amount of nitrogen precipitated show that the
      absolute chemical method for the estimation of antibody actually measures
      antibody and not antibody plus a more or less indefinite amount of non-specific
      protein. An objection to the use of the method is thus shown to be unfounded.

PMID- 19870380
TI  - THE PRECIPITIN REACTION BETWEEN TYPE III PNEUMOCOCCUS POLYSACCHARIDE AND
      HOMOLOGOUS ANTIBODY : III. A QUANTITATIVE STUDY AND A THEORY OF THE REACTION
      MECHANISM.
AB  - The precipitin reaction between the specific polysaccharide of Type III
      pneumococcus and homologous antibody formed in the horse can be accounted for
      quantitatively by assuming the chemical combination of the components in a
      bimolecular reaction, followed by a series of competing bimolecular reactions
      which depend upon the relative proportions of the components. These reactions
      would lead to the formation of larger and larger aggregates until precipitation
      ultimately occurred. The mathematical formulation of this theory on the basis of
      the mass law is described. The derived expressions are shown to be in accord with
      the experimental findings and the constants used in these expressions are shown
      to have definite significance. In spite of the wide variation in the properties
      of individual sera these expressions permit the complete description of the
      behavior of an unknown serum with S III without an unduly burdensome number of
      analyses. The quantitative theory presented has been found applicable to other
      instances of the precipitin reaction, as will be shown in subsequent papers.

PMID- 19870381
TI  - THE RELATION OF LEUKOSIS TO SARCOMA OF CHICKENS : I. SARCOMA AND ERYTHROLEUKOSIS
      (STRAIN 13).
AB  - A transmissible strain of sarcoma (Strain 13) is described that took its origin
      in a chicken inoculated with leukosis of Strain 1. The virus of Strain 13
      produces sarcoma in the breast muscle injected with it and after intravenous
      inoculation it produces diffuse sarcomatosis of the spleen, bone marrow, and
      several other organs. The available evidence suggests that Strain 13 is caused by
      a single virus with ability to produce diffuse endothelial growth in the blood
      forming organs associated with extensive hematomata, and erythroblastic
      proliferation. The strain can be readily transmitted by material free from live
      cells and preserved by drying. As small amounts of blood as 0.00001 cc. from
      chickens with sarcomatosis of the internal organs transmit Strain 13 by the
      intravenous route. By implantation sarcoma of Strain 13 can be transferred to
      chickens that are resistant to repeated inoculations with leukotic viruses.

PMID- 19870382
TI  - THE EXTENT OF LOCAL DISPERSION OF INFECTIOUS AGENTS AS A FACTOR IN RESISTANCE TO
      INFECTION.
AB  - Progressively decreasing quantities of bacteria of some 20 strains were utilized
      in experiments upon the effect of dispersing the organisms in the rabbit skin
      through the agency of an extract of testicle or an invasive staphylococcus. The
      same was done with 6 strains of filterable viruses. The bacterial lesions were
      enhanced by spreading when the organisms introduced were above a certain number
      or quantity (minimal effective concentration) and on the other hand were
      partially or totally suppressed when their number was less than this. Virulence
      and minimal effective concentration were observed to be in inverse relationship.
      The lesions due to the filterable viruses studied were, on the other hand,
      enhanced by the spreading factor even when the quantity of virus approached the
      minimal infective dose. This happened irrespective of whether the virus caused
      severe lesions or slight ones. The highly virulent Pneumococcus Type I, injected
      into normal rabbits together with the spreading factor, yielded enhanced lesions
      even at practically its minimal infective dose; but when the resistance of the
      animal was raised with specific antiserum the lesions were totally suppressed by
      the experimental dispersion of the bacteria. When such an experiment was repeated
      on a filterable virus, vaccinia, no suppression took place as a result of the
      dispersion of the infective agent. The significance of the differences in the
      bacterial and virus phenomena is discussed.

PMID- 19870383
TI  - STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS.
AB  - Experiments on the sensitization of guinea pigs with simple chemical compounds
      are described. Positive effects were obtained by the administration of small
      quantities, namely fractions of milligrams, with 1:2:4 chlorodinitrobenzene, p
      nitrosodimethylaniline, 1:2:4 trinitrobenzene, picryl chloride, four
      dichlorodinitrobenzenes, and a number of other aromatic compounds. Several
      substances chemically similar to those enumerated gave negative results. The
      first named compound is known to produce hypersensitiveness in human beings, a
      large number of cases having been observed in factory workers. The mechanism of
      these effects is discussed.

PMID- 19870384
TI  - THE FIXATION AND PROTECTION OF VIRUSES BY THE CELLS OF SUSCEPTIBLE ANIMALS.
AB  - Methods were developed for a study of the relations existing between viruses and
      living cells. It was found that vaccinia and the virus causing the infectious
      fibroma of rabbits (Shope) rapidly become fixed upon tissue cells freed as
      individuals and submitted to virus in suspension. This happens whether the cells
      are alive or have been killed with heat or ultraviolet light. The virus does not
      come away during agitation of the cells with Tyrode solution and repeated
      washings with large amounts of it. The exposure to neutralizing antisera of cells
      carrying virus fails to affect this latter significantly if the cells are alive,
      whereas if they are dead the activity of the virus is nullified. Cells freed as
      individuals from tissue cultures of vaccinia and the Shope tumor carry these
      viruses in abundance through repeated washings, and, if living, protect them from
      the influence of a neutralizing serum, whereas killed cells exert no such
      protection. The findings would appear to throw light on the way in which viruses
      gain a foothold in the host; and they suggest reasons for the persistence of some
      viruses in recovered animals and for the unsatisfactory results of serum
      treatment instituted during the course of virus diseases. The virus causing the
      Shope fibroma has been successfully maintained in cultures of the growth. It is
      closely associated with the cells, almost none being present in the culture
      fluid. Certain of its other attributes have been determined. Vaccinia greatly
      damages the cells of cultures of rabbit embryo in which it is under propagation.

PMID- 19870385
TI  - ENCEPHALOMYELITIS ACCOMPANIED BY MYELIN DESTRUCTION EXPERIMENTALLY PRODUCED IN
      MONKEYS.
AB  - The repeated intramuscular injections of aqueous emulsions and alcohol-ether
      extracts of sterile normal rabbit brains in some manner produced pathological
      changes accompanied by myelin destruction in the brains of 7 of 8 monkeys
      (Macacus rhesus). Eight, control monkeys remained well. Cultures from the
      involved brains remained sterile, and no transmissible agent was demonstrated by
      means of intracerebral inoculations of emulsions of bits of the brains into
      monkeys, rabbits, guinea pigs, and white mice.

PMID- 19870386
TI  - THE RELATION BETWEEN THE TYPE SPECIFIC CARBOHYDRATES OF PNEUMOCOCCI AND THE BLOOD
      GROUP SPECIFIC SUBSTANCE A.
AB  - 1. A relationship between the soluble specific substances of pneumococci and the
      blood group substance A of man can be demonstrated by the inhibition of sheep
      cell hemolysis by a group specific A-antiserum. However, there are quantitative
      differences between the various types. 2. A striking difference exists between
      the acetyl and the de-acetylated polysaccharide of Pneumococcus Type I: The de
      acetylated carbohydrate fails to react with the group specific A-antiserum, while
      the acetyl carbohydrate shows a strong reactivity. 3. The minimum amount of the
      acetyl polysaccharide, which inhibits sheep cell hemolysis by A-antiserum, is
      almost as small as that of the group specific carbohydrate isolated by
      Freudenberg and Eichel from urines of group A. 4. The reactivity of the acetyl
      polysaccharide can be demonstrated not only by the hemolysis inhibition test, but
      also by complement fixation and by inhibition of group specific iso
      agglutination. 5. Feces filtrates, which possess the ability to destroy the blood
      group specific substances A and B of man, also affect the acetyl polysaccharide
      of Pneumococcus Type I. After incubation with an effective feces filtrate, the
      acetyl polysaccharide almost completely loses its potency toward the group
      specific A-antiserum and also its ability to inhibit the iso-agglutination of A
      blood cells. 6. Acetyl polysaccharide of Pneumococcus Type I, having lost its
      reactivity toward the group-specific A-antiserum after treatment with feces
      filtrate, still reacts with Type I pneumococcus antiserum which was previously
      absorbed with de-acetylated polysaccharide, Type I. Thus, the essential effect of
      the feces filtrate on acetyl polysaccharide, Type I, is not the cleavage of
      acetyl group, but some other chemical alteration.

PMID- 19870387
TI  - NUTRITIONAL EDEMA IN THE DOG : II. HYPOALBUMINEMIA AND THE AUGMENTATION OF TISSUE
      FLUID.
AB  - The manner in which edema develops in dogs maintained on a diet low in protein is
      described. Pre-edematous fullness of the tissues is observed for some weeks
      before palpable edema develops. The state of pre-edema does not merge gradually
      with that of true edema but rather the transition is relatively sudden. Among
      twenty dogs the time required for the production of edema varied from 35 to 100
      days and averaged 61 days. With three animals in which the nitrogen metabolism
      was studied during the period before edema had developed, the observed loss of
      weight was consistently less than the theoretical loss of weight calculated from
      the negative nitrogen balance. Reasons are given for interpreting the discrepancy
      as evidence of increasing retention of fluid during the stage of pre-edema. In
      general the weight curve does not rise during the transition from pre-edema to
      edema. However, the weight does increase rapidly when fluid is accumulating in
      the peritoneal cavity. The level of serum albumin which is critical for the
      development of edema varied between 1.04 and 2.17 gm. per cent. The range is
      sufficiently wide to suggest the existence of other factors of importance in
      determining the exact time of appearance of edema. During the phase of recovery
      the level of albumin which is critical for the disappearance of edema may be
      appreciably higher than the level which was critical for the formation of edema.
      Among thirty samples of edema fluid the protein concentration was from 0.02 to
      0.72 gm. per cent. The average protein level was 0.230 and the median level 0.165
      gm. per cent. A positive correlation is not demonstrable between the duration of
      edema and the protein content of edema fluid. A difference in behavior toward
      fluid retention between subcutaneous tissue and peritoneal cavity is pointed out.
      Subcutaneous tissue is more resistant to acute stress and less resistant to
      prolonged or repeated stress than the peritoneal cavity. The role of tissue
      pressure in the etiology of edema is discussed. It is suggested that the critical
      level of protein in the serum is the concentration which permits the attainment
      in the tissue spaces of mechanical pressure great enough to break down the
      restraining action of the connective tissue boundaries of the spaces.

PMID- 19870388
TI  - STUDIES ON BACTERIAL LOCALIZATION : EFFECTS OF SPECIFIC IMMUNIZATION AND OF A GUM
      ACACIA MEDIUM ON LOCALIZATION OF TYPE I PNEUMOCOCCI IN MICE.
AB  - THE RESULTS OF GROSS AND MICROSCOPIC OBSERVATIONS AND SURVIVAL TESTS AFTER
      SUBCUTANEOUS INFECTION OF MICE WITH TYPE I PNEUMOCOCCI CAN BE SUMMARIZED AS
      FOLLOWS: Normal mice possessed no adequate means of protection against this
      organism. The bacteria disseminated freely through the tissue spaces in the
      presence of widespread inflammation, and were not ingested by significant numbers
      of host cells. Macrophages mobilized in the subcutis by intraperitoneal
      vaccinations with homologous killed organisms promptly ingested the living
      bacteria subsequently introduced. The cocci were sharply localized and destroyed
      in the presence of minimal amounts of exudation, edema and necrosis. Bacterial
      localization accompanied a similar hypoergic reaction after passive immunization.
      When a hyperergic response was induced by repeated local, in addition to
      intraperitoneal, vaccinations, prompt phagocytosis by macrophages, as after
      intraperitoneal vaccination alone, was again the outstanding means of disposal of
      the organisms. The heightened exudation, edema and local necrosis resembled a
      harmful rather than an important localizing reaction. Immunity was not dependent
      upon a hyperergic reaction. Prompt in vivo agglutination of living bacteria after
      passive immunization was an important early localizing phenomenon. After either
      active or passive immunization, phagocytosis was the only means observed by which
      the organisms were destroyed. Thus localization and destruction of the bacteria
      in immunized mice were dependent both on bacterial changes caused by specific
      antibody and on phagocytic activities of host cells. A viscous gum acacia medium
      caused a transient delay in bacterial dissemination, but the organisms ultimately
      became widely scattered in the tissues of the abdominal wall. The animals died
      earlier, with more extensive and destructive lesions than when the bacteria were
      introduced in a saline medium. In distinct contrast, the pneumococci were as a
      rule sharply localized and destroyed when injected in an acacia medium containing
      a small amount of immune serum. After local active immunization, sufficient to
      protect about half the animals subsequently infected by pneumococci in a saline
      medium, extensive and destructive lesions and death of the mice followed
      introduction of the organisms in acacia. It was suggested that the more viscous
      medium may have hindered diffusion of immune bodies from the tissues into the
      inoculum.

PMID- 19870389
TI  - STUDIES ON MENINGOCOCCUS INFECTION : VIII. THE TYPE I SPECIFIC SUBSTANCE.
AB  - The Type I meningococcus specific substance has been isolated and purified. It
      appears to be a sodium salt of a polysaccharide acid.

PMID- 19870390
TI  - THE CELLULAR REACTIONS TO ACETONE-SOLUBLE FAT FROM MYCOBACTERIA AND STREPTOCOCCI
      : THE EFFECT OF NEUTRALIZATION ON THE BIOLOGICAL ACTIVITY OF THE TUBERCULO-LIPOID
      AND OF THE PHTHIOIC ACID DERIVED FROM IT.
AB  - 1. The acetone-soluble fat of tubercle bacilli produces a profound cellular
      reaction when injected into normal animals. The reaction involves every type of
      connective tissue cell. Hemorrhage, formation of adhesions and of tubercular
      tissue occur. The extent of the reaction is roughly proportional to the amount of
      material injected. 2. The reaction induced by the lipoid is much less extensive
      and much simpler when the material is neutralized with alkali. Neutralization of
      the acetone-soluble fat, or of phthioic acid, does not diminish the
      tuberculogenic property. 3. Acetone-soluble fat from streptococci is likewise
      extremely irritating but does not produce tubercular tissue.

PMID- 19870391
TI  - THE FORMATION OF AGGLUTININS WITHIN LYMPH NODES.
AB  - Agglutinins are formed within the draining lymph nodes of mice, following
      intradermal injections of killed cultures of microorganisms.

PMID- 19870392
TI  - RABBIT POX : III. REPORT OF AN EPIDEMIC WITH ESPECIAL REFERENCE TO
      EPIDEMIOLOGICAL FACTORS.
AB  - A devastating epidemic of rabbit pox in a breeding colony was studied with
      especial reference to factors of epidemiological significance. The evidence
      obtained indicated that the epidemic originated among animals inoculated with
      vaccine virus and that the infection was spread to the breeding colony by
      caretakers. The epidemic began insidiously with atypical cases of visceral
      disease followed by typical cases of pox and terminated as a mild cutaneous
      disease with scattering monosymptomatic affections of various kinds, difficult to
      recognize as cases of pox infection. An analysis of data concerning the health
      and functional efficiency of the population and the immunity of exposed animals
      showed that the epidemic of rabbit pox was the terminal event in a series of
      progressive disorders which began fully a month before the first case of pox
      occurred. In like manner, the terminal decrease in the severity of the disease
      and the eventual termination of the epidemic appeared to be referable to an
      improvement in the condition of the population rather than to a specific immunity
      acquired by exposure to infection.

PMID- 19870393
TI  - MULTIPLICATION IN VITRO OF PSEUDORABIES VIRUS IN THE TESTICLE TISSUE OF IMMUNIZED
      GUINEA PIGS.
AB  - Pseudorabies virus was cultivated in vitro in washed testicle tissue from immune
      guinea pigs, and evidence was thus procured which indicated that the testicle
      cells themselves had not become immune to pseudorabies. The rate of
      multiplication of the virus was considerably greater in control cultures with
      normal guinea pig testis than in cultures with immune testis. The reason for this
      fact may be that even by repeated washing the immune tissue could not be
      completely freed from fluid antibodies, and that such antibodies somewhat
      inhibited the multiplication of the virus.

PMID- 19870394
TI  - STUDIES ON THE SUPRARENAL CORTEX : IV. THE EFFECT OF SODIUM SALTS IN SUSTAINING
      THE SUPRARENALECTOMIZED DOG.
AB  - 1. A group of experiments is reported in which bilaterally suprarenalectomized
      adult male dogs have been maintained in apparently normal condition over
      prolonged periods, up to 5 months, without the use of any suprarenal gland
      preparation or extract and by the administration of sodium chloride and sodium
      bicarbonate alone. Withdrawal of the salts then produced typical suprarenal
      insufficiency. 2. The relation of the absence of free hydrochloric acid in the
      gastric juice of suprarenalectomized animals, in addition to, or independent of
      the factor of dehydration, for the production of anorexia and hypoglycemia, is
      discussed. 3. Further evidence is presented in these experiments in support of
      the view that the suprarenal cortical hormone in the adult male dog is concerned
      with the regulation of sodium excretion by the kidney, and thus eventually with
      the proper maintenance of water balance in the organism. It has no direct
      influence on carbohydrate metabolism. 4. The reciprocal changes in the plasma
      concentrations of urea and of potassium which take place as the concentrations of
      plasma sodium and chlorides vary, are pointed out as furnishing a mechanism
      whereby abrupt alterations in osmotic pressure are dampened, and the volumes of
      fluids in extracellular and intracellular compartments more efficiently
      stabilized.

PMID- 19870395
TI  - THE EFFECT OF FASTING ON THE SERUM PROTEIN CONCENTRATION OF THE RAT : WITH
      SPECIAL REFERENCE TO THE QUESTION OF THE EXISTENCE OF AN IMMEDIATELY UTILIZABLE
      CIRCULATING PROTEIN FRACTION.
AB  - 1. Experiments were carried out to test the hypothesis that there exists a
      special circulating fraction of plasma protein available for use by the tissues.
      2. The changes in serum protein concentration after varying periods of fasting
      were followed in large numbers of individual rats. 3. Previous reports from this
      laboratory of a small initial drop in the total protein concentration of the
      serum, with subsequent maintenance of the serum protein at the new level are
      confirmed. 4. Evidence is offered that this initial fall involves chiefly or
      solely the albumin fraction. 5. The mechanism responsible for the observed
      initial drop and subsequent maintenance of the protein is not exactly known, but
      two definite factors are age and individual resistance. 6. It is concluded that
      no satisfactory evidence is available to support the hypothesis of a directly
      utilizable protein fraction in the blood.

PMID- 19870396
TI  - EXPERIMENTS ON THE EPIDEMIOLOGY OF PSEUDORABIES : II. PREVALENCE OF THE DISEASE
      AMONG MIDDLE WESTERN SWINE AND THE POSSIBLE ROLE OF RATS IN HERD-TO-HERD
      INFECTIONS.
AB  - Study of the pseudorabies virus-neutralizing antibody content of pooled and
      individual samples of swine serum have led to the conclusion that pseudorabies is
      a highly prevalent, unrecognized, disease in middle western hogs. It has been
      shown that wild brown rats develop a fatal infection following ingestion of
      pseudorabies virus and that their carcasses, in turn, give rise to the disease in
      swine to which they are fed. It is believed that rats play a role in the
      epidemiology of porcine pseudorabies, serving as the initial source of infection
      for a swine herd and also as one means by which virus can be spread from farm to
      farm in swine herds. The experiments presented furnish further evidence that
      swine may serve as the source of infection for cattle.

PMID- 19870397
TI  - THE IMMUNOLOGICAL SPECIFICITY OF STAPHYLOCOCCI : I. THE OCCURRENCE OF SEROLOGICAL
      TYPES.
AB  - 1. Agglutination is not a precise method for the demonstration of serological
      types among staphylococci. 2. Precipitation of soluble specific substance derived
      from these organisms demonstrates the existence of at least two immunologically
      distinct types. 3. The one type, designated A, is composed of apparently virulent
      strains, while the other, Type B, contains the avirulent strains. 4.
      Precipitation tests performed with centrifugates of young broth cultures or with
      acid extracts of sedimented bacteria may also demonstrate type specificity. 5.
      Lysis by bacteriophage fails to detect the specific types of Staphylococcus. 6.
      Immunization by intravenous methods stimulates agglutinin formation in all
      rabbits and precipitin formation in only one of three or four animals. 7.
      Immunization by repeated intracutaneous injections of dead staphylococci or
      living organisms in an agar focus also stimulates agglutinin formation but fails
      to incite the formation of type specific precipitins.

PMID- 19870398
TI  - EFFECT OF ANAEROBICALLY PREPARED PNEUMOCOCCUS AUTOLYSATE TOXIN ON MICE AND
      EVALUATION OF PNEUMOCOCCUS AUTOLYSATE ANTITOXIN IN MICE.
AB  - 1. Certain anaerobically produced autolysates of pneumococcus injected
      intravenously kill mice in 0.1 to 0.2 cc. quantities in a few hours to 8 days. 2.
      The symptoms of mice inoculated with these autolysates are weakness and
      increasing prostration until death. Massive albuminuria is found, appearing 18
      hours after injection. During the course of a prolonged intoxication ascites and
      edema of the subcutaneous tissues may develop. Large pale yellow or white kidneys
      are found in mice that survive 5 days. In these latter animals, emaciation is
      usually marked at death. 3. The antitoxin prepared in horses by immunization with
      the anaerobically prepared toxic autolysates of pneumococcus neutralizes the
      poisonous autolysates whether mixed in vitro before injection or injected
      separately after the autolysate. 4. The injection of pneumococcus autolysate
      toxin incompletely neutralized with autolysate antitoxin causes a protracted
      intoxication with symptoms and pathologic findings similar to those found in mice
      dying slowly after injections of the toxic autolysate alone.

PMID- 19870399
TI  - THE IMMUNOLOGICAL SPECIFICITY OF STAPHYLOCOCCI : II. THE CHEMICAL NATURE OF THE
      SOLUBLE SPECIFIC SUBSTANCES.
AB  - 1. Two carbohydrates have been extracted from different strains of Staphylococcus
      which are immunologically and chemically distinct. 2. The chemical differences
      between the two types are manifested principally in optical rotation, and in the
      simple sugars resulting from hydrolytic cleavage of the specific carbohydrates.
      3. The immunological specificity of both polysaccharides is dissipated as
      hydrolysis proceeds. 4. The results of the chemical reactions reported are
      discussed.

PMID- 19870400
TI  - THE IMMUNOLOGICAL SPECIFICITY OF STAPHYLOCOCCI : III. INTERRELATIONSHIPS OF CELL
      CONSTITUENTS.
AB  - 1. The carbohydrates derived from Staphylococcus are type specific. 2. The
      specific carbohydrates fail to induce formation of antibodies in rabbits. 3.
      Acetylation or adsorption of the carbohydrates on collodion particles does not
      render them antigenic. 4. The specific carbohydrates may be employed to elicit
      immediate, type specific, skin reactions in patients with Staphylococcus
      infection. 5. The protein of Staphylococcus is species specific. 6. The protein
      is antigenic and stimulates in rabbits species specific antibodies. 7. The
      protein causes in hypersensitive individuals a species specific, delayed,
      inflammatory skin reaction.

PMID- 19870401
TI  - THE DEGREE OF DISPERSION OF THE BACILLUS AS A FACTOR IN INFECTION AND RESISTANCE
      IN EXPERIMENTAL TUBERCULOSIS.
AB  - 1. The skin lesions in rabbits and guinea pigs following intradermal injection of
      tubercle bacilli (5 strains) were greatly increased in size and severity when
      testicle extract was added to the inoculum. Such enhancement was followed by a
      more widespread and rapidly progressing disease only when virulent strains were
      employed. 2. Attempts to suppress the development of skin lesions resulting from
      the injection of either normal or tuberculous rabbits with very small quantities
      of tubercle bacilli mixed with testicle extract were unsuccessful. 3. The skin
      reactions of tuberculous guinea pigs to tuberculo-protein MA 100 were greatly
      increased in size and markedly reduced in intensity by the addition of testicle
      extract to the protein solution. The toxic effect of larger quantities of
      tuberculo-protein was not altered by the addition of testicle extract. 4. The
      dispersion of tubercle bacilli through the skin of tuberculous rabbits resulted
      in a marked enhancement of the Koch phenomenon but was not followed by any
      extension of the new infection to the viscera. Tuberculous rabbits infected on
      two occasions with dead tubercle bacilli suspended in testicle extract showed an
      increased resistance to the disease when compared with controls receiving dead
      bacilli suspended in saline solution. 5. The resistance conferred upon
      tuberculous guinea pigs by superinfection was greatly increased when the bacilli
      employed were dispersed through the skin with testicle extract. 6. The parenteral
      administration of large quantities of testicle extract to recently infected
      guinea pigs did not result in any increase in the extent of the visceral lesions.
      7. The partial immunity conferred upon guinea pigs and rabbits by vaccination
      with heat-killed tubercle bacilli was increased as a result of dispersion of the
      vaccine through the skin with testicle extract.

PMID- 19870402
TI  - IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS : I. PREPARATION OF
      ELEMENTARY BODIES OF VACCINIA.
AB  - By means of differential centrifugation in the horizontal and angle centrifuges
      it is possible to obtain appreciable quantities of relatively pure elementary
      bodies of vaccinia. Such preparations of elementary bodies exhibit an extremely
      high titer of vaccine virus. The elementary bodies are specifically agglutinated
      by serum from rabbits immunized by means of injections of bacteria-free vaccine
      virus. Virus-free filtrates of dermal vaccine virus and of bacteria-free
      testicular vaccine virus contain a soluble substance or substances that is
      precipitated by antivaccinal sera.

PMID- 19870403
TI  - INTERSTITIAL BRONCHOPNEUMONIA : I. SIMILARITY OF A TOXIN PNEUMONIA TO THAT
      PRODUCED BY THE VIRUSES.
AB  - Bacterial toxins can produce a pneumonia similar to that caused by viruses, and
      the presence of a toxin-producing bacterium in the lungs may account for some of
      the interstitial bronchopneumonias observed in diseases other than those caused
      by viruses.

PMID- 19870404
TI  - EXPERIMENTS ON THE EPIDEMIOLOGY OF PSEUDORABIES : I. MODE OF TRANSMISSION OF THE
      DISEASE IN SWINE AND THEIR POSSIBLE ROLE IN ITS SPREAD TO CATTLE.
AB  - Pseudorabies is a very fatal but non-contagious disease in cattle and the common
      laboratory animals. It is a relatively mild yet highly contagious disease in
      swine. It has been shown that in swine the nose serves both for the entrance and
      the exit of the virus. Furthermore, it has been observed that fatal pseudorabies
      infections in rabbits can be induced merely by bringing their abraded skin into
      contact with the noses of infected swine. The blood sera of swine on two farms
      where pseudorabies had occurred among the cattle were found to be capable of
      neutralizing pseudorabies virus. It is believed that in these instances the swine
      had a mild and unrecognized pseudorabies infection and transmitted their disease
      to the cattle with which they were associated, by transfer of the virus on their
      noses to the abraded skin of the cattle.

PMID- 19870405
TI  - STUDIES ON THE IMMUNE RESPONSE OF THE RHEUMATIC SUBJECT AND ITS RELATIONSHIP TO
      ACTIVITY OF THE RHEUMATIC PROCESS : I. THE DETERMINATION OF ANTISTREPTOLYSIN
      TITER.
AB  - 1. A method for determining the antistreptolysin titer is described in detail. 2.
      The natural human level of antistreptolysin determined in this way is
      approximately 50 units.

PMID- 19870406
TI  - STUDIES ON THE IMMUNE RESPONSE OF THE RHEUMATIC SUBJECT AND ITS RELATIONSHIP TO
      ACTIVITY OF THE RHEUMATIC PROCESS : II. OBSERVATIONS ON AN EPIDEMIC OF INFLUENZA
      FOLLOWED BY HEMOLYTIC STREPTOCOCCUS INFECTIONS IN A RHEUMATIC COLONY.
AB  - THE OBSERVATIONS PRESENTED IN THIS PAPER MAY BE SUMMARIZED AS FOLLOWS: A study
      has been made on an isolated group of children with heart disease. All of these
      individuals, with one exception, were rheumatic subjects. Many of them carried a
      strain of hemolytic streptococcus in the throat flora during the winter of 1934.
      The organism produced no detectible toxin and was not associated with respiratory
      disease. Four patients contracted chicken pox during the winter months. None
      developed rheumatic recrudescences. All of the individuals were in good health on
      March 1. A severe epidemic of influenza began on March 22. All but six children
      contracted the disease. The filterable virus responsible for this outbreak was
      recovered. This agent did not activate the rheumatic process. It was followed by
      an outbreak of streptococcus infection and appeared to facilitate its spread. The
      source of these infections was not traced. They were due to a single type of
      hemolytic streptococcus which was a strong toxin producer. Its cultural,
      biochemical and serological characteristics were different from those of the
      carrier strain. Of seventeen individuals proven bacteriologically to be infected
      with the epidemic strain, fourteen rheumatic subjects developed acute rheumatism,
      two rheumatic subjects and one patient with congenital heart disease escaped.
      These fourteen rheumatic attacks were accompanied by a rise in antistreptolysin
      titer coincident with the onset of symptoms. In four of these attacks it was
      possible to exclude influenza as a causative factor. The clinical observations,
      the bacteriological findings and the immunological evidence indicate that this
      severe outbreak of rheumatic fever was caused by Streptococcus hemolyticus, which
      appeared to be a single strain by type.

PMID- 19870407
TI  - STUDIES ON THE IMMUNE RESPONSE OF THE RHEUMATIC SUBJECT AND ITS RELATIONSHIP TO
      ACTIVITY OF THE RHEUMATIC PROCESS : III. OBSERVATIONS ON THE REACTIONS OF A
      RHEUMATIC GROUP TO AN EPIDEMIC INFECTION WITH HEMOLYTIC STREPTOCOCCUS OF A SINGLE
      TYPE.
AB  - This study of an isolated colony showed that of seven children who escaped the
      epidemic streptococcus infection none developed rheumatic symptoms; and that of
      seventeen children who contracted the epidemic streptococcus infection, fourteen
      developed acute rheumatism and three showed no recognizable rheumatic
      manifestations. The seven children who failed to contract infection with
      Streptococcus hemolyticus showed clearly that susceptible individuals may live in
      dose association with an epidemic of acute rheumatism, develop no rise in
      antistreptolysin titer and maintain excellent health. The patient with congenital
      heart disease demonstrated that a non-rheumatic subject may be infected with a
      highly effective strain of hemolytic streptococcus, and develop a typical
      antibody response, yet escape all rheumatic manifestations. The two patients who,
      although infected with the epidemic strain, failed to show any antibody response,
      also failed to develop rheumatic recrudescences. Environmental, dietary, age and
      the other factors investigated did not appear to be significant in this outbreak
      of acute rheumatism. Three factors appeared to determine the development of the
      fourteen recrudescences: (1) infection with a highly effective agent; (2) the
      disease pattern, peculiar to each rheumatic subject; (3) the intensity of the
      immune response of the patient as indicated by the rise in antistreptolysin
      titer.

PMID- 19870408
TI  - THE PURIFICATION OF THE ANTIBODIES IN TYPE I ANTI-PNEUMOCOCCUS SERUM, AND THE
      CHEMICAL NATURE OF THE TYPE-SPECIFIC PRECIPITIN REACTION.
AB  - 1. Methods for the concentration of Type I pneumococcus antibody have been
      outlined. 2. The physical and chemical properties of the purified antibody have
      been described. 3. The chemical basis of serological specificity has been
      discussed.

PMID- 19870409
TI  - PATHOGENIC ORGANISMS OF THE GENUS LISTERELLA.
AB  - From meningitis in man, encephalitis in cattle and sheep, a myocardial infection
      in fowl, and a generalized infection in rabbits, different observers have
      isolated Gram-positive organisms which are closely related. Their cultural and
      serological properties are described. When injected intravenously into chickens,
      rabbits, or guinea pigs there is an unusual blood response, the monocytes being
      markedly increased. The organisms tend to localize in the myocardium with
      resulting necrosis.

PMID- 19870410
TI  - THE INFLUENCE OF LATENT SYPHILITIC INFECTION ON THE REACTION OF THE RABBIT TO THE
      BROWN-PEARCE TUMOR.
AB  - The reaction of the latent syphilitic rabbit to inoculation with the Brown-Pearce
      tumor was studied in 50 standard bred rabbits representing five breeds. The mean
      tumor mortality rate in the combined group was found to be significantly lower
      than a weighted control value for normal non-syphilitic animals, and the mean
      tumor mortality rate for each of the five breeds studied was lower in the
      syphilitic group than the corresponding breed mean value for normal animals.
      Moreover, the relative resistance of different breeds to the Brown-Pearce tumor
      was not altered by the latent syphilitic infection. Certain factors which might
      have contributed to the development of a tumor resistant state in the syphilitic
      group were discussed, and evidence was presented which demonstrates that as
      regards the breeds under consideration, there exists a high correlation between
      breed resistance to Tr. pallidum infection and breed resistance to the Brown
      Pearce tumor.

PMID- 19870411
TI  - SPREADING PROPERTY OF AZOPROTEINS IN THE DERMIS.
AB  - 1. Azoproteins are shown to have the property of spreading when introduced
      intradermally into the rabbit skin. 2. The aromatic derivative selected for the
      coupling does not affect specifically the spreading property of the azoprotein.
      Likewise, the type of protein has no importance, except in quantitative respects.
      3. The spreading property conferred upon a protein by coupling appears to derive
      from the presence of the azo group. 4. The spreading power of an azoprotein
      preparation seems to be determined by the number of diazo groups which enter the
      protein molecule, and to vary in direct proportion with the concentration of the
      solution. 5. Azo compounds of low molecular weight fail to exhibit any
      significant effect on skin permeability.

PMID- 19870412
TI  - ISOLATION OF POLIOMYELITIS VIRUS FROM THE NASOPHARYNX.
AB  - A single example of mild illness diagnosed as suspected abortive poliomyelitis is
      described in which the virus of poliomyelitis was recovered from the nasopharynx
      by three different methods. Failure to recover virus from a total of twenty-six
      cases diagnosed as suspected or abortive poliomyelitis and fourteen contacts is
      also reported. The original material from the nasopharynx of the positive case
      proved unusually infective for the monkey, apparently even more so than are the
      majority of suspensions of spinal cords from fatal human cases of poliomyelitis.
      An explanation of this fact is not clear. The method of isolating human virus
      from the throat, by means of preserving the sediment of washings from this site
      in glycerine, has been shown to be efficient in one case for a period of 101
      days.

PMID- 19870413
TI  - THE USE OF GRADED COLLODION MEMBRANES FOR THE CONCENTRATION OF A BACTERIAL ENZYME
      CAPABLE OF DECOMPOSING THE CAPSULAR POLYSACCHARIDE OF TYPE III PNEUMOCOCCUS.
AB  - 1. The enzyme which decomposes the capsular polysaccharide of Type III
      Pneumococcus is associated with a protein which under optimal conditions of
      filtration passes through membranes with an average pore size of 10.6 mmicro but
      is held back by pores having a diameter of 8.2 mmicro. 2. When enzyme solutions
      are filtered to dryness through membranes of such porosity as to hold back the
      active principle, and when proper precautions are taken to prevent or minimize
      adsorption, the enzyme can be completely recovered in solution by immersing the
      membrane in distilled water or physiological salt solution. 3. These results are
      discussed with reference to the dimensions of the enzyme particle, and to the
      purification obtained in the course of ultrafiltration. 4. A practical method is
      described for the concentration and purification of the crude enzyme preparation
      by the use of graded collodion membranes.

PMID- 19870414
TI  - SEROLOGICAL RELATIONSHIP BETWEEN PNEUMOCOCCUS TYPE I AND AN ENCAPSULATED STRAIN
      OF ESCHERICHIA COLI.
AB  - An encapsulated strain of Escherichia coli has been isolated which is hemolytic,
      pathogenic for mice, and which has served to illustrate further evidence of
      heterogenetic specificity. The relationship appears to be limited to the
      serological reactions between the colon organism and Type I antipneumococcic
      horse serum. Type I antipneumococcic rabbit serum failed to agglutinate the
      organism and no reactions occurred with Types II and III antipneumococcic horse
      serums, normal horse serum, and a variety of other immune horse serums. Serum
      from rabbits immunized with the colon bacillus agglutinated the homologous
      organism and precipitated its soluble substance, but failed to cause
      agglutination of Type I pneumococci or to precipitate Type I pneumococcic
      polysaccharide. The evidence indicates a connection somewhat analogous to that
      between Type II pneumococcus and Type B Friedlander's bacillus.

PMID- 19870415
TI  - THE ANTIGENIC RELATIONSHIP BETWEEN BACILLUS PROTEUS X-19 AND RICKETTSIAE : III. A
      STUDY OF THE ANTIGENIC COMPOSITION OF THE EXTRACTS OF BACILLUS PROTEUS X-19.
AB  - Two substances differing in immunological behavior as well as in certain chemical
      properties have been isolated from soluble extracts of B. proteus X-19. Both
      substances appear to be polysaccharides. The first substance is precipitated from
      X-19 crude extracts by a relatively low percentage of alcohol and electrolytes
      (from one to two and a half volumes of alcohol). When purified as far as
      possible, it gives a negative biuret reaction, a positive Molish and has a
      nitrogen content of 4 per cent. This material, which we call X factor, has the
      immunological properties of the common antigenic factor in Proteus X-19 and
      typhus Rickettsiae, described elsewhere. It has the property of precipitating
      with typhus serum as well as anti-Proteus serum, even after treatment with hot
      alkali. The second substance we call P factor, suggesting a material which is
      proper to Proteus X-19 and has nothing to do with the Weil-Felix reaction. It is
      obtained from the crude extracts of B. proteus X-19 by treating the fluids from
      which the X factor has been removed with an excess of alcohol (seven to ten
      volumes, according to electrolytes in solution). The purified material shows a
      nitrogen content of a little less than 1 per cent, gives a negative biuret and a
      positive Molish reaction. The P factor produces precipitates with anti-Proteus
      serum in considerable dilution, but has no effect on typhus serum. It is quickly
      destroyed on treating with alkali, a fact in accordance with the results already
      cited, which were obtained by White with whole extracts of B. proteus X-19. The
      duality of the X-19 extracts seems to be explained by the isolation of two
      immunologically different factors; one which is alkali-labile and which is proper
      to B. proteus X-19; and the other which is alkali-stable and is the common
      antigenic factor in Proteus X-19 and typhus Rickettsiae.

PMID- 19870416
TI  - A MODIFIED METHOD OF OBTAINING LARGE AMOUNTS OF RICKETTSIA PROWAZEKI BY ROENTGEN
      IRRADIATION OF RATS.
AB  - The radiation method described by Zinsser and Castaneda for obtaining large
      amounts of Rickettsia has been carried out successfully with an ordinary
      radiographic machine. This allows the extension of the method to those
      communities which do not possess a high voltage Roentgen therapy unit as
      originally employed.

PMID- 19870417
TI  - RABBIT POX : IV. SUSCEPTIBILITY AS A FUNCTION OF CONSTITUTIONAL FACTORS.
AB  - The epidemiological significance of age, race, sex, genetic constitution and
      physiological status were studied by means of a differential analysis of the
      mortality data derived from a devastating epidemic of rabbit pox and, with the
      exception of sex, were found to be factors of the utmost importance in the
      determination of susceptibility. Young animals were more susceptible than adults
      and although the most susceptible age varied with the epidemic phase, it
      corresponded in general with the period of weaning. The influence of
      physiological status was further indicated by the increased susceptibility
      incident to lactation. Racial variations in susceptibility were obscured by age
      factors in young animals, but were of profound importance in the adult population
      and formed the most significant feature of the analysis. A high degree of
      conformity was found in the susceptibility of racially related breeds, and this
      similarity in behavior increased with the proximity of relationship. Moreover, a
      study of the hybrids obtained from the crossing of pure breeds showed that two
      separable groups of hereditary factors were concerned in the determination of
      breed susceptibility, one group consisting of essential racial characters, the
      other of constitutional factors incorporated in the stock by chance association,
      and that the final expression of susceptibility or resistance was the result of
      their combined interaction.

PMID- 19870418
TI  - RABBIT POX : REPORT OF AN EPIDEMIC.
AB  - Observations on an epidemic of rabbit pox occurring in an isolated animal room
      during the winter of 1933-34 are reported. The clinical manifestations,
      consisting of a generalized papular eruption involving the skin and mucous
      membranes, together with blepharitis, ophthalmia, nasal discharge and
      lymphadenopathy were essentially similar to those noted in a pox epidemic of the
      previous year. This was true in general also of the pathological findings except
      that vacuolization, local necrosis and vesicle formation were seen in the
      epidermis, while in the previous year the microscopic pathology in the skin was
      confined to the corium. Evidence was presented indicating that the infection can
      be transmitted through the medium of a personal carrier, and that transmission in
      this manner can occur during the incubation period or before a definite diagnosis
      is possible. The findings also demonstrated that the etiological agents
      responsible for the disease reported here and that of the previous year were
      immunologically related, and that the immunity in recovered animals effectively
      persisted during the entire period for which data are available, 9 to 12 months.
      It appeared also that young animals suckling an immune doe were more refractory
      to the development of the lesions of rabbit pox than were the young of
      susceptible does.

PMID- 19870419
TI  - IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS : II. CHEMICAL
      ANALYSIS OF ELEMENTARY BODIES OF VACCINIA.
AB  - Washed elementary bodies obtained from dermal vaccine virus contain ash,
      carbohydrate, fat, and nitrogen a part of which is undoubtedly in the form of
      protein. These components are similar to those found in bacteria and other
      substances of protoplasmic origin.

PMID- 19870420
TI  - BARTONELLA BODIES IN THE BLOOD OF A NON-SPLENECTOMIZED DOG.
AB  - A non-splenectomized dog, on a vitamin-adequate basal diet, in the course of a
      plasmapheresis experiment, developed an uncontrollable anemia associated with the
      presence of bodies in or on the erythrocytes, indistinguishable from the
      descriptions of Bartonella canis. The normal plasma protein level of 7.3 per cent
      was reduced to 4.1 per cent by diet and the removal of 5354 ml. of whole blood in
      33 bleedings. The Bartonella infection was transferred to a splenectomized dog by
      an intravenous injection of whole blood. Each animal was apparently sterilized by
      one injection of neoarsphenamine equivalent to 15 mg. per kilo weight. It is
      possible that the spleen liberates some substance into the blood stream which has
      an inhibitory effect upon a latent Bartonella infection and that this protective
      substance was diminished by the many bleedings associated with the lowering of
      plasma proteins in the non-splenectomized dog and was lacking in the inoculated
      splenectomized dog.

PMID- 19870421
TI  - THE PROTECTIVE ACTION OF TYPE I ANTIPNEUMOCOCCUS SERUM IN MICE : I. THE
      QUANTITATIVE ASPECTS OF THE MOUSE PROTECTION TEST.
AB  - The mouse protection test for the evaluation of type specific antipneumococcus
      serum has been studied with reference to the quantitative relationships between
      the amount of antibody and the number of injected bacteria. By varying both these
      factors through wide limits certain definite characteristics of the protection
      test have been defined. These are the Schwellenwert, the prozone, and the
      limiting titer zone. The modifications produced in the manifestations of these
      characteristics by changes in the technic of performing the test and also by
      certain non-specific reagents are described. The dependence of the outcome of the
      test upon variable factors intrinsic to the host is discussed.

PMID- 19870422
TI  - THE PROTECTIVE ACTION OF TYPE I ANTIPNEUMOCOCCUS SERUM IN MICE : II. THE COURSE
      OF THE INFECTIOUS PROCESS.
AB  - Observations are reported which concern the nature of the infectious process
      resulting from the intraperitoneal injection of mice with virulent pneumococci.
      The course of the infection has been figuratively reconstructed on the basis of
      the following data: The rate of bacterial multiplication, the numbers of cells
      present in the peritoneal cavity, the character of these cells at various stages,
      and the rate of phagocytosis. The significant alterations in this infectious
      process brought about by the administration of type specific immune serum are
      described, and the general significance of the findings discussed with reference
      to the functions of the immune serum and the role of phagocytes in protection.

PMID- 19870423
TI  - THE PROTECTIVE ACTION OF TYPE I ANTIPNEUMOCOCCUS SERUM IN MICE : III. THE
      SIGNIFICANCE OF CERTAIN HOST FACTORS.
AB  - The power of specific antipneumococcus serum to protect mice against infection
      with Type I Pneumococcus has been studied with reference to the capacity of the
      animal to utilize the specific antibodies. With a single strain of mice it was
      found that smaller animals and those with large numbers of white cells in the
      peritoneal cavity are much better able to utilize the passively conferred immune
      principles. These two intrinsic factors were resolved into a single element;
      namely, the number of monocytes in the peritoneal cavity at the time of injection
      of culture and serum. The interrelation of the extrinsic and intrinsic factors
      participating in the process of protection have been discussed.

PMID- 19870424
TI  - AN APPARATUS FOR THE CULTURE OF WHOLE ORGANS.
AB  - An apparatus has been developed which maintains, under controllable conditions, a
      pulsating circulation of sterile fluid through organs for a length of time
      limited only by the changes in the organ and in the perfusion fluid.

PMID- 19870425
TI  - RIFT VALLEY FEVER : A REPORT OF THREE CASES OF LABORATORY INFECTION AND THE
      EXPERIMENTAL TRANSMISSION OF THE DISEASE TO FERRETS.
AB  - Three cases of Rift Valley fever in human individuals are reported. The virus was
      recovered from the respiratory tract of the patients and was transmitted to
      ferrets by the intranasal route. The experimental disease so produced in ferrets
      is characterized by fever, marked pulmonary lesions, and hemorrhagic phenomena.
      The results indicate that the virus of Rift Valley fever belongs to the group of
      filterable viruses which may gain entrance to the human body through the
      respiratory tract. The differential diagnosis of Rift Valley fever and influenza
      is discussed. While, clinically, this is a difficult problem, the diagnosis may
      be readily established through animal experimentation. Certain observations
      concerning the influence of the route of administration on the protective action
      of immune serum in serum-virus mixtures are presented.

PMID- 19870426
TI  - INTERSTITIAL BRONCHOPNEUMONIA : II. PRODUCTION OF INTERSTITIAL MONONUCLEAR
      PNEUMONIA BY THE BORDET-GENGOU BACILLUS.
AB  - Pure cultures of Bordet-Gengou bacilli produce in rabbits an interstitial
      mononuclear pneumonia which cannot be differentiated from that occurring in
      children dying of pertussis or from lhat caused in animals by the viruses of
      epidemic influenza and psittacosis. A similar pneumonia can be produced in
      rabbits by typhoid bacilli.

PMID- 19870427
TI  - HEMOGLOBIN REGENERATION IN THE CHRONIC HEMORRHAGIC ANEMIA OF DOGS (WHIPPLE) : I.
      THE EFFECT OF IRON AND PROTEIN FEEDING.
AB  - 1. A group of dogs on a standard salmon bread diet with a slowly regenerating
      anemia were studied. The addition of liver to this diet during a 2 week period
      promoted a definitely greater regeneration of hemoglobin than did the addition of
      an amount of inorganic iron which was equivalent to that contained in the added
      liver. The more effective result attained with liver cannot, therefore, be
      attributed solely to the iron intake. 2. The greater response to liver is not due
      to its content of amino acids which are present in casein, since a diet
      containing an exactly similar amount of calories, iron and protein nitrogen, made
      up of inorganic iron and casein does not cause a greater response than that
      obtained by the addition of that amount of inorganic iron alone to the standard
      basal diet. 3. Furthermore, the salmon bread diet does not produce a deficiency
      of the amino acids represented in casein, since dogs eating the high protein
      (casein) Cowgill dog ration show the same basal hemoglobin regeneration rate and
      a similar greater response to liver than to inorganic iron. The Cowgill ration,
      however, supplies some non-ferrous factor involved in hemoglobin regeneration
      which is not contained, to as great a degree at least, in the salmon bread. 4.
      Whipple's chronic hemorrhagic anemia of dogs serves as an accurate assay method
      for measuring the hemoglobin producing power of a substance. Quantitatively
      reproducible responses can be obtained.

PMID- 19870428
TI  - A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION : II. A STUDY OF AN AZOPROTEIN
      ANTIBODY SYSTEM.
AB  - 1. A quantitative theory of the precipitin reaction based on the laws of
      classical chemistry has been tested on an azoprotein-antiprotein system and found
      to apply. 2. With its aid relationships may be deduced which permit the
      calculation of the behavior of an antidye serum over its entire range after a few
      quantitative chemical analyses have been made for antigen and antibody in the
      precipitate. 3. An empirical relation is also presented which further reduces the
      number of analyses necessary. 4. A study of supernatants in the inhibition zone
      has shown that the entire amount of dissolved antigen-antibody compound present
      is precipitated when supernatants are analyzed for antigen by the precipitin
      method.

PMID- 19870429
TI  - LIPOIDS AND IMMUNOLOGICAL REACTIONS : I. THE RELATION OF PHOSPHOLIPINS TO THE
      TYPE-SPECIFIC REACTIONS OF ANTIPNEUMOCOCCUS HORSE AND RABBIT SERA.
AB  - It has been demonstrated that the removal of lipoids from Type I antipneumococcus
      horse serum causes a loss of the visible phenomena of type specific agglutination
      and precipitation, and in the case of rabbit serum a marked reduction in these
      properties. Initial activity of the type specific antibody can be restored to
      extracted immune horse serum by the addition of lecithin, and to rabbit serum by
      the addition of cephalin. The significance of these observations in respect to
      the relation of phospholipins to the type specific reactions of antipneumococcus
      serum is discussed.

PMID- 19870430
TI  - IMMUNOLOGICAL STUDIES WITH THE VIRUS OF INFLUENZA.
AB  - Following infection with the virus of influenza, both ferrets and mice develop a
      state of active immunity to reinfection. The serum of these animals contains
      neutralizing antibodies, as evidenced by the capacity of the serum to confer
      passive protection to mice against infection with the P.R.8 and Phila. strains of
      the virus of human influenza. Rabbits which are apparently insusceptible to
      infection with the virus of influenza produce specific antibodies in response to
      repeated injection of virus-containing material. The serum of immunized rabbits
      affords passive protection to mice against mouse-virulent virus. Although the
      subcutaneous or intraperitoneal injection of the living virus does not produce
      infection in mice, animals so treated acquire active immunity against subsequent
      infection by the intranasal route. Neutralization tests with the serum of
      patients before and after recovery from influenza, pneumonia and the common cold
      indicate that neutralizing antibodies arise as a specific response to infection
      with the virus of influenza. The immunological identity of strains of influenza
      virus recovered from human sources has been established, and the possible
      existence of strains of related, but not identical, antigenic structure is
      discussed.

PMID- 19870431
TI  - INACTIVATION OF POLIOMYELITIS VIRUS IN VITRO BY CRYSTALLINE VITAMIN C (ASCORBIC
      ACID).
AB  - The experimental evidence presented in this paper shows that multiple paralytic
      doses of poliomyelitis virus, when mixed with very small amounts of crystalline
      vitamin C (ascorbic acid), are rendered non-infectious as determined by
      intracerebral injection of such mixtures into rhesus monkeys.

PMID- 19870432
TI  - THE PROGRESSION TO CARCINOMA OF VIRUS-INDUCED RABBIT PAPILLOMAS (SHOPE).
AB  - The papillomas induced in domestic rabbits with virus procured from cottontails
      undergo progressive changes in the direction of malignancy when they grow
      vigorously. From the beginning they exhibit the traits whereby tumors are
      characterized, and they have malignant potentialities. In seven animals of a
      group of ten carrying papillomas for more than 200 days, cancer has developed,
      and in an eighth a tumor of problematic malignancy has arisen. One of the
      remaining two rabbits died early in the cancer period, and the papillomas of the
      other eventually retrogressed. Ten cottontails with induced growths of much
      longer duration have not developed cancer. The malignant tumors have all been
      acanthomatous in type, and have arisen directly from the papillomas by graded,
      continuous alterations. These have often gone further after malignancy has been
      attained, and have eventuated in great anaplasia. Metastasis has been frequent,
      and transplantation to another host has proved successful. Individual growths
      have occurred expressive of each stage of the transformation to cancer, as if
      through a stabilization at this stage; yet despite the variety thus afforded, the
      tumors must all be looked upon as the consequence of alterations in cells of a
      single sort, namely epidermal cells affected by the virus, and the alterations
      themselves have taken a single direction. In the morphology of many of the
      cancers the influence of the virus is still manifest. The better the papilloma
      grew, the more likely was cancer to occur, and the greater was the tendency to
      multiple tumors. In the most favorable rabbits malignant changes took place at
      numerous locations in the papillomatous tissue, and were imminent at many others.
      Intercurrent factors had much to do with determining frank carcinosis; and when
      the tendency to it was not marked their influence sometimes seemed crucial.
      Analogous instances of a graded alteration from papilloma to cancer are frequent
      in human pathology. The virus that gives rise to the rabbit papillomas must be
      looked upon as the primary cause of the cancers developing therefrom. Whether it
      is their proximate cause has yet to be determined.

PMID- 19870433
TI  - JENNERIAN PROPHYLAXIS BY MEANS OF INTRADERMAL INJECTIONS OF CULTURE VACCINE
      VIRUS.
AB  - The second revived strain of culture vaccine virus has been propagated through
      130 culture passages during a period of 3 years. It seems to be adapted to in
      vitro cultivation and still has an intradermal titer (rabbits) of 1 to 100,000 or
      1 to 1,000,000. Intradermal inoculations in human beings of 0.1 cc. amounts of
      culture virus diluted from 2.5 to 10 times result in primary takes in
      unvaccinated people and immune reactions or accelerated takes in individuals
      previously successfully vaccinated. Primary takes produce an immunity to standard
      strains of calf lymph. Culture virus mixed with purified gum acacia (2.5 per
      cent), frozen, desiccated, and sealed in vacuo retains its activity for a month
      at 37 degrees C., and when the dried virus is resuspended in saline solution it
      is suitable for intradermal vaccination of human beings.

PMID- 19870434
TI  - THE INFECTION OF MICE WITH SWINE INFLUENZA VIRUS.
AB  - The experiments confirm the earlier observation of Andrewes, Laidlaw and Smith
      that the swine influenza virus is pathogenic for white mice when administered
      intranasally. Two field strains of the swine influenza virus were found to differ
      in their initial pathogenicity for mice. One strain was apparently fully
      pathogenic even in its 1st mouse passage while the other required 2 or 3 mouse
      passages to acquire full virulence for this species. Both strains, however, were
      initially infectious for mice, without the necessity of intervening ferret
      passages. There is no evidence that bacteria play any significant role in the
      mouse disease though essential in that of swine, and fatal pneumonias can be
      produced in mice by pure virus infections. Mice surviving the virus disease are
      immune to reinfection for at least a month. In mice the disease is not contagious
      though it is notably so in swine. The virus, while regularly producing fatal
      pneumonias when administered intranasally to mice, appears to be completely
      innocuous when given subcutaneously or intraperitoneally. Prolonged serial
      passage of the virus in mice does not influence its infectivity or virulence for
      swine or ferrets. It is a stable virus so far as its infectivity is concerned,
      and can be transferred at will from any one of its three known susceptible hosts
      to any other. In discussing these facts the stability of the swine influenza
      virus has been contrasted with the apparent instability of freshly isolated
      strains of the human influenza virus. Though the mouse is an un-natural host for
      the virus it is, nevertheless, useful for the study of those aspects of swine
      influenza which have to do with the virus only.

PMID- 19870435
TI  - CUTANEOUS REACTIVITY OF IMMUNE AND HYPERSENSITIVE RABBITS TO INTRADERMAL
      INJECTIONS OF HOMOLOGOUS INDIFFERENT STREPTOCOCCUS AND ITS FRACTIONS.
AB  - Rabbits were immunized intravenously with intact indifferent streptococci, with
      homologous P fraction, and with an emulsion of mechanically ground cocci; others
      were sensitized by intravenous injection of the intact microorganisms. Their
      serologic and dermal reactions to these materials and to the homologous S
      fraction were compared with those of normal animals. The dissociation, in certain
      instances, between circulating antibody and dermal reactivity was noteworthy.
      From the results the following conclusions were drawn. 1. Intradermal injection
      of a soluble streptococcal protein into a rabbit immunized intravenously with
      that protein leads to the immediate anaphylactic type of skin response; while
      similar dermal testing of a rabbit sensitized by intracutaneous inoculation of
      the intact microorganism induces the delayed (tuberculin) type of response. 2.
      The induction of the immediate type of dermal reaction to streptococcal protein
      requires more than the mere presence of a high serum precipitin titer to that
      protein. 3. Lesions of the immediate type can be induced by the intradermal
      injection of a streptococcal carbohydrate into rabbits immunized intravenously
      with intact cocci and showing a high serum precipitin titer to that carbohydrate.
      4. Intravenous immunization of rabbits with an emulsion of mechanically ground
      indifferent streptococci leads to the production of only non-type-specific
      antibodies. 5. It is possible that carbohydrate as well as protein fractions of
      indifferent streptococci are capable of eliciting the delayed type of dermal
      response in rabbits intracutaneously sensitized with that microorganism.

PMID- 19870436
TI  - DISTRIBUTION OF BLOOD GROUP PROPERTIES AND BLOOD GROUP PROPERTY DESTROYING
      FACTORS IN THE INTESTINAL TRACT OF MAN.
AB  - 1. The blood group specific substance A is present in the contents of the jejunum
      and upper ileum of persons belonging to Group A. 2. A marked decrease in the
      amount of A substance occurs in the lower ileum and cecum, while colon and rectum
      contents of adults are more or less free of group substance A. 3. The blood group
      destroying agent first appears in the lower ileum or cecum and its effectiveness
      increases in the lower parts of the large intestine. 4. In two cases with
      intestinal obstruction the blood group destroying agent could be demonstrated in
      the contents of the jejunum and ileum.

PMID- 19870437
TI  - BILE FISTULAS AND RELATED ABNORMALITIES : BLEEDING, OSTEOPOROSIS, CHOLELITHIASIS
      AND DUODENAL ULCERS.
AB  - A clearer understanding of the various abnormalities which may develop in
      relation to the experimental or clinical bile fistula will be of value to the
      laboratory worker as well as to the physician and surgeon. A better comprehension
      of these diseased conditions will make for a saner analysis of the great mass of
      experimental data relating to the various types of bile fistula. Too frequently
      in the literature the bile fistula material is used to debate a physiological
      state whereas in reality the animal is in a pathological condition. It is
      possible but not easy to keep a bile fistula dog in a normal state for months or
      years if proper attention is given to the diet and physical state. The most
      significant abnormalities are-intestinal disturbances, spontaneous bleeding,
      osteoporosis, cholelithiasis and duodenal ulcer. Three types of bile fistula were
      used in our experiments and each one has its advantages and disadvantages.
      Intestinal intoxication is best controlled by diet, by whole bile or bile salts
      or combinations of dog and ox bile. Spontaneous bleeding seems to be due to the
      loss of something by way of the bile and this can be prevented by bile feeding.
      The blood deficiency appears to be a lack of prothrombin. Osteoporosis appears
      inevitably after many months if bile is excluded from the intestine. This state
      is related to the lack of absorption of vitamin D. It is of some interest that
      liver feeding will prevent it. Duodenal ulcers and cholelithiasis are common in
      bile fistula dogs and absolute control or prevention is not easy. It may be
      restated that bile secretion into the intestine is necessary for normal health
      and even for actual continuation of life beyond a few months' period. Some of
      these experimental data should be of value to physicians and surgeons in the care
      and study of human fistula cases and should emphasize the necessity of prompt
      dietary control.

PMID- 19870438
TI  - THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: ELICITATION OF
      LOCAL REACTIVITY BY WAY OF THE VASCULAR SYSTEM.
AB  - The skin of the rabbit's ear is considerably more resistant than the abdominal
      skin to the phenomenon of local skin reactivity to bacterial filtrates. Ten times
      the provocative dose is required if it is given into the vein of the prepared ear
      and thirty times the provocative dose if it is given into the vein of the non
      prepared ear. The state of reactivity cannot be elicited by a preparatory
      intravenous injection of bacterial filtrates alone into clamped and non-clamped
      ears. The state also fails to appear in combination with cold, xylol, ethyl
      urethane, pilocarpine hydrochloride, atropine, calcium gluconate, guinea pig
      liver extract, histamine dihydrochloride, adrenalin chloride, and pituitrin.
      Preparatory intravenous injections of toxins are capable of eliciting the state
      of reactivity in the rabbit's ear when they are accompanied by thermal hyperemia
      (i.e., exposure to 45 degrees , 50 degrees , and 55 degrees C.). It is also
      possible to induce the state of reactivity when a mixture of the preparatory
      factors with testicular extract is given into the veins of clamped ears. The
      incubation period required may be less than 2 hours. In the light of the above
      experiments, there are discussed various observations concerning the elicitation
      of the phenomena of organ reactivity by means of live bacterial cultures and the
      filtrates thereof.

PMID- 19870439
TI  - THE COLONY MORPHOLOGY OF TUBERCLE BACILLI : III. THE RELATION BETWEEN VIRULENCE
      AND COLONY FORM.
AB  - All the strains of human tubercle bacilli described in this report as recently
      isolated from clinical cases proved to be virulent and showed but slight
      differences in pathogenic properties. Neither did they show extreme variation in
      virulence when compared with Strain H-37, isolated many years ago. Between twelve
      bovine strains cultivated in vitro for varying periods, there was a much wider
      range in virulence, some being so attenuated as to give regressive lesions in
      both rabbits and guinea pigs, while other strains were highly pathogenic. In
      general, the more recently isolated strains were the more virulent. Attenuation
      occurs with prolonged in vitro cultivation, but the rate of attenuation is
      apparently not the same for all strains. Studies of cultures recovered from
      inoculated animals demonstrated that in the case of bovine tubercle bacilli
      virulence is correlated with three phenomena: the number of bacilli which can be
      stained in tissues of inoculated animals, the number of organisms recoverable in
      cultures from the tissues, and the proportion of smooth colonies in these
      cultures. All cultures of either human or bovine type recovered from animals
      showed either two or three types of colonies. In general the percentage of the
      smooth form varied directly with virulence. However, some smooth colonies were
      present in strains having little or no pathogenicity. One example was cited of an
      avian strain which had lost its virulence while retaining the smooth colony form
      indicating that, although pathogenicity is usually correlated with smooth colony
      form, it is not necessarily so. And smooth variants devoid of virulence do occur.
      In the comparison of the effect of the same human strain on rabbits and guinea
      pigs, it was shown that native resistance (of the rabbit) was associated with a
      power to dissociate the inoculated bacilli into a greater proportion of rough
      forms, and then to destroy them. This power is not possessed by the naturally
      susceptible animal (guinea pig).

PMID- 19870440
TI  - THE COMPARATIVE BEHAVIOR OF MAMMALIAN EGGS IN VIVO AND IN VITRO : I. THE
      ACTIVATION OF OVARIAN EGGS.
AB  - 1. A definite chronological sequence of events occurs in the eggs and follicles
      of rabbits after mating or after the injection of ovulation-inducing substances.
      The follicle secretes secondary liquor folliculi, and there occurs a separation
      of the corona radiata from strands connecting it to the follicle cells. The ovum
      goes through nuclear maturation with as climax the production of the first polar
      body by the 8th hour after copulation. 2. Thyroxin injections cause indirectly
      the same effects as mating or pituitary injections but no ovulation occurs. The
      thyroxin effect occurs later than the pituitary effect and is due to an
      initiation of atresia in the follicles. 3. Explantation of ova results in typical
      maturation phenomena which are apparently unaffected by the presence of pituitary
      hormones or of thyroxin in the culture medium. 4. It is concluded that maturation
      of the ovum can be obtained simply by isolating it from the normal follicular
      environment. 5. Normal fertilization can be secured with eggs removed from the
      follicles.

PMID- 19870441
TI  - EPIDEMIOLOGY OF EQUINE ENCEPHALOMYELITIS IN THE EASTERN UNITED STATES.
AB  - Equine encephalomyelitis of the eastern type is a disease of the late summer and
      fall and cases are found in greatest numbers near salt marshes. The
      epidemiological findings are against its transmission by contact and favor the
      view that it is insect borne. Although virus can be demonstrated in the blood of
      infected horses it is present for a relatively short time, and the possibility
      that the disease is not primarily an infection of horses but that it is
      transmitted to them from another host is considered.

PMID- 19870442
TI  - THE TRANSMISSION OF EQUINE ENCEPHALOMYELITIS VIRUS BY AEDES AEGYPTI.
AB  - In confirming Kelser's work on the transmission of equine encephalomyelitis of
      the western type by Aedes aegypti it has been learned that the mosquitoes must be
      fed virus of high titer if positive results are to be secured. A period of from 4
      to 5 days after feeding either on infected guinea pigs or on brain containing
      virus must elapse before the disease is transmitted by biting, but after this
      time transmission regularly results for a period of about 2 months. By
      inoculation, virus can be demonstrated in the bodies of infected mosquitoes for
      the duration of life. Although virus multiplies in the mosquitoes and is
      generally distributed in their bodies, repeated attempts to demonstrate it in the
      eggs from females known to be infected as well as in larvae, pupae, and adults
      from such eggs have been uniformly negative. Larvae have not taken up virus added
      to the water in which they were living. Male mosquitoes have been infected with
      virus by feeding but they have not transmitted the virus to normal females, nor
      have males transmitted the virus from infected to normal females. When virus of
      the eastern instead of the western type is used transmission experiments with
      Aedes aegypti are negative. Apparently this virus is incapable of penetrating the
      intestinal mucosa of the mosquito. If, however, it is inoculated into the body
      cavity by needle puncture it persists and transmission experiments are positive.

PMID- 19870443
TI  - A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION : III. THE REACTION BETWEEN
      CRYSTALLINE EGG ALBUMIN AND ITS HOMOLOGOUS ANTIBODY.
AB  - 1. A quantitative theory of the precipitin reaction based on the laws of
      classical chemistry has now been found applicable to the crystalline egg albumin
      antibody system. Equations derived from the theory permit the calculation of the
      behavior of an anti-egg albumin serum over most of the reaction range after a few
      quantitative analyses have been made for the nitrogen precipitated. Data of other
      workers also conform to the proposed equations. 2. The empirical relation, shown
      to have advantages in the dye antidye system, may also be used for the Ea-A
      reaction. 3. Serum from the same animal after successive courses exhibits
      progressive changes which have been described graphically and quantitatively.
      These changes are believed to consist in the formation of more and more antibody
      capable of reacting with a larger number of chemically different groupings in the
      antigen molecule. 4. Evidence is presented that anti-egg albumin is not
      homogeneous, and that even after prolonged immunization the antiserum contains
      much low-grade antibody, incapable of forming precipitates unless more reactive
      precipitin is present. 5. Factors affecting the equivalence point ratio are
      discussed.

PMID- 19870444
TI  - FURTHER OBSERVATIONS ON THE BLOOD CHOLESTEROL OF RABBITS IN RELATION TO
      ATHEROSCLEROSIS.
AB  - 1. The action of potassium iodide in preventing a significant rise in the blood
      cholesterol of rabbits fed cholesterol was temporary. After about 4 months it
      lost its effectiveness and the blood cholesterol rose. 2. In rabbits with
      hypercholesterolemia resulting from long continued cholesterol feeding, the
      administration of potassium iodide caused a marked rise in the blood cholesterol.
      3. On the other hand, dried whole thyroid given to such animals produced a sharp
      fall in the blood cholesterol. This fall was temporary and was followed by a rise
      to new high levels. 4. In thyroidectomized rabbits fed cholesterol and potassium
      iodide, both thyroid and thyroxin delayed but did not prevent a rise in blood
      cholesterol. Even with the hypercholesterolemia in these animals, however, the
      incidence of atherosclerosis was low. 5. Age apparently played a part in
      determining the response of the blood cholesterol to cholesterol feeding. In a
      group of old rabbits when compared with a younger group the rise in the
      cholesterol of the blood was greater and the subsequent return toward normal was
      slower when the feeding was stopped.

PMID- 19870445
TI  - SEROLOGICAL EVIDENCE OF IMMUNITY WITH COEXISTING SENSITIZATION IN A TYPE OF HUMAN
      ALLERGY (HAY FEVER).
AB  - Using ragweed hay fever as the representative of a certain type of allergy we
      have made studies to determine if possible the mechanism of the protection
      afforded by specific injections thus far established only by clinical
      observation. 1. Blood transfusions and serum injections from clinically immune,
      treated patients stopped the clinical reaction in untreated patients, thus
      indicating a transferable immunity. 2. The amount of skin sensitizing antibody in
      the serum was found to be practically unchanged by specific injections. 3.
      Injection of allergen-antibody mixtures into normal skin showed an immediate (1
      hour) reaction when sites were made if serum of untreated cases (Serum A) was
      used but none or slight reaction if serum of treated cases (Serum P) was used. 4.
      When sites made with allergen-antibody mixtures were tested after 48 hours,
      reactions were absent with Serum A mixtures if enough allergen had been used, but
      were positive with mixtures of Serum P even though a much stronger allergen was
      contained in the mixture. 5. The primary inhibition of reactions with mixtures
      including Serum P was not due to antihistamine effect nor to binding of skin
      sensitizing antibody nor to binding or lysis of allergen. 6. The inhibiting
      antibody appears to be specific. 7. These serological studies supported by
      transfusion experiments have been interpreted by us as showing the development
      under treatment of a peculiar blocking or inhibiting type of immune antibody that
      prevented the action of allergen on the sensitizing antibody and hence showed in
      the type of human allergy under consideration (hay fever) the coexistence of
      sensitization and immunity.

PMID- 19870446
TI  - CELLULAR REACTIONS TO WAX-LIKE MATERIALS FROM ACID-FAST BACTERIA : THE
      UNSAPONIFIABLE FRACTION FROM THE TUBERCLE BACILLUS, STRAIN H-37.
AB  - 1. The unsaponifiable fractions of the Mycobacteria, though insoluble in water
      and extremely stable chemical compounds, are nevertheless remarkable stimulants
      of cells. 2. They give rise to new monocytes which surround these waxes and then
      fuse into giant cells which engulf them. 3. The property of acid-fastness of the
      waxes makes it possible to identify them within the giant cells which have
      phagocytized them. 4. Within the foreign body giant cells the waxes are slowly
      disintegrated. They appear not to damage the cells which engulf them, and hence
      one may infer that they take no part in caseation. 5. They have no effect on the
      resistance of the host.

PMID- 19870447
TI  - CELLULAR REACTIONS TO WAXES FROM MYCOBACTERIUM LEPRAE.
AB  - 1. The waxes from the B. leprae, like those from tubercle bacilli, are remarkable
      stimulants of cells. 2. The crude wax separated from the B. leprae is a mixture
      of lipoids and other materials, and gives reactions that include the types of
      cells characteristic of the response to the tuberculo-polysaccharide,
      phosphatide, and wax. 3. The wax obtained from the purification of the lepra
      phosphatide shows similar cellular reactions but with a greater proportion of
      foreign body giant cells. 4. Leprosin, though a glyceride, corresponds in its
      physical properties to the unsaponifiable material from the tubercle bacillus. It
      stimulates two strains of cells, fibroblasts and monocytes. The monocytes fuse
      into foreign body giant cells to engulf the wax. 5. The cellular reaction to the
      leprosinic acid and to the crystalline alcohols is of one type only, represented
      by the foreign body giant cell.

PMID- 19870448
TI  - THE EFFECTS OF NASALLY INSTILLED VIRUS OF POLIOMYELITIS ON THE CEREBROSPINAL
      FLUID AND THE BLOOD OF MONKEYS.
AB  - Macacus rhesus and Macacus cynomolgus exhibit a striking sensitivity to the
      presence of the virus of poliomyelitis on the nasal mucous membranes.
      Irrespective of whether detectable symptoms of clinical poliomyelitis do or do
      not arise in the nasally instilled animals, the cerebrospinal fluid changes
      quickly in response to virus placed in the nasal passages. Two sets of changes
      occur in the cerebrospinal fluid: the constant and most pronounced change
      consists of increase in the content of white cells, chiefly of the lymphocytic
      type; the inconstant and less profound one consists of detectable amounts of
      globulin in the fluid (free from red corpuscles) withdrawn by cisterna puncture.
      As early as 48 hours after instillation of the virus, a marked increase in cells
      is already detectable in the fluid; the increase grows from day to day, reaching
      a maximum sometimes in another day or two, sometimes not until 4, 5, or 6 more
      days elapse. In many instances a rise of temperature follows or coincides with
      the rising tide of cells; and the onset of clinical symptoms of disease bears
      also a relation to the cell count. The number of cells in the cerebrospinal fluid
      and the temperatures tend to be higher in monkeys which develop paralytic
      symptoms; occasionally exceptions to this rule occur, in which instilled monkeys
      remaining asymptomatic exhibit high cell counts; very rarely do the latter show
      the higher temperatures. Monkeys once instilled which fail to become
      symptomatically affected again react by cerebrospinal fluid changes to later
      courses of instillation. A second or still later course may induce paralysis; or
      highly exceptional or refractory animals may go through several courses of
      instillation without developing clinical symptoms, although never failing to
      respond with changes in the cerebrospinal fluid. The virus instillations of
      Macacus monkeys do not lead to active immunization unless clinical symptoms of
      infection have resulted from the inoculations and attended the cerebrospinal
      fluid changes. In the complete absence of clinical symptoms the instilled animals
      fail to develop blood antiviral properties, and they are as susceptible to the
      cerebral injection of virus as are the control monkeys. On the other hand,
      instilled monkeys which have shown even mild and fleeting (abortive) clinical
      symptoms of infection, resist cerebral inoculation and exhibit blood antiviral or
      neutralizing properties. Monkeys which have developed clinical symptoms of
      disease and have recovered are, as stated, actively immunized; they remain,
      however, sensitive to the presence of virus on the nasal membrane, reacting with
      cerebrospinal fluid changes, differing only in degree from the nonimmune animals.
      Detectable virus does not appear in the pleocytic cerebrospinal fluid at any
      stage of the pathological processes. The current belief is that mass immunization
      is proceeding in an unperceived manner through the chance entrance of virus into
      the nasal passages of children. It is not known whether, apart from all symptoms
      of disease, cerebrospinal fluid changes occur in the course of this unexpressed,
      spontaneous process. A large gap seems to exist between man and the monkey in the
      capacity of the former to become immunized by way of the nasal membrane, and the
      inability of the latter to do so. It is common knowledge that monkeys do not
      become immune through unsuccessful cerebral inoculations of virus, and the same
      seems to be true of the nasal channel of virus penetration into the central
      nervous organs.

PMID- 19870449
TI  - FURTHER STUDIES ON THE SUBMAXILLARY GLAND VIRUSES OF RATS AND GUINEA PIGS.
AB  - 1. It has not been possible to increase the virulence of the submaxillary gland
      viruses of guinea pigs and rats, either by reducing the resistance of the animals
      by exposure to X-ray, or by the addition of testicular extract (Duran-Reynals
      factor). 2. In guinea pigs and wild rats with spontaneously infected submaxillary
      glands, the kidney has been found to contain the virus in the absence of
      demonstrable pathological changes. 3. Direct injection of these viruses into the
      kidney produces only mild, circumscribed lesions. 4. The viruses, following
      subcutaneous injection into white rats and guinea pigs, are widely distributed 2
      weeks after injection. They are present in the submaxillary glands, cervical
      lymph nodes, kidney, and lung. They were not demonstrable at this time in the
      blood, liver, or spleen. 5. By the intratracheal injection of large doses of
      virus in guinea pigs and rats, an interstitial bronchopneumonia with thickening
      of the alveolar and bronchial walls and the presence of acidophilic inclusion
      bodies, can be produced. 6. No evidence was obtained to indicate that the
      multiplication of bacteria in the lung is greatly enhanced by the injection of
      these viruses.

PMID- 19870450
TI  - THE DISTRIBUTION OF SWINE INFLUENZA VIRUS IN SWINE.
AB  - Swine influenza virus was found to be regularly present in the turbinates,
      tracheal exudate and lungs of infected swine but not in the spleens, livers,
      kidneys, mesenteric lymph nodes, colon mucosae, brains or blood. It was present
      in low concentration in the bronchial lymph nodes of 2 out of 8 animals. This
      localization of the virus in swine accords with its classification as a
      pneumotropic virus.

PMID- 19870451
TI  - EXPERIMENTAL STUDIES ON ENCEPHALITIS : IV. SPECIFIC INACTIVATION OF VIRUS BY SERA
      FROM PERSONS EXPOSED TO ENCEPHALITIS, ST. LOUIS TYPE, 1933 WITH A NOTE ON THE
      EVALUATION OF THE RESULTS OF MOUSE TESTS OF SERA.
AB  - 1. A protection test for measuring serological protective properties against the
      encephalitis (St. Louis type) virus is described. 2. Normal non-contact sera and
      sera from persons supposed to have had no exposure to the disease do not protect
      against the virus. 82.5 per cent of sera from tested St. Louis encephalitis
      convalescents and at least 66 per cent of sera from tested persons thought to
      have had the disease do show protective properties. 3. The protective activity of
      sera is maintained for at least 2(1/2) years after onset of the disease. In vitro
      aging of serum decreases its activity. 4. Protection tests indicate that the
      virus was present as early as 1932 in Paris, Illinois, spread through the north
      central states and reached New York in 1933, and was again active in the north
      central states in 1934.

PMID- 19870452
TI  - THE EMIGRATION OF PNEUMOCOCCI TYPE III FROM THE BLOOD INTO THE THORACIC DUCT
      LYMPH OF RABBITS, AND THE SURVIVAL OF THESE ORGANISMS IN THE LYMPH FOLLOWING
      INTRAVENOUS INJECTION OF SPECIFIC ANTISERUM.
AB  - 1. Rabbits injected intravenously with a large dose of a virulent Type III
      Pneumococcus develop a bacteremia, and within an hour organisms may be cultivated
      from the thoracic duct lymph. The rapidity with which entrance into the lymph
      occurs appears to be correlated with the size of the dose injected. 2. The
      organisms may become more numerous in the lymph than in the blood. 3. If
      homologous or heterologous antisera are injected, the blood may be sterilized,
      but though the organisms may be lessened in the lymph, sterilization at least
      within 4 hours is not secured, and in the intact animal living organisms must
      continue to enter the blood with the thoracic duct lymph. 4. In infected rabbits
      after intravenous injection of considerable quantities of antisera containing
      moderate amounts of agglutinin, no antibody appears in the thoracic duct lymph
      although the presence of horse serum may be detected. The injection of a very
      large quantity of antiserum containing a high titre of agglutinin is followed by
      the penetration of antibody into the lymph. This, however, has failed to
      sterilize the lymph or to permanently affect the rate of multiplication of the
      pneumococci.

PMID- 19870453
TI  - STUDIES ON THE TOXIN PRODUCTION OF THE SHIGA BACILLI.
AB  - 1. The S, R, and R(n) variants of the Shiga bacillus are equally toxic. 2. The
      effect of the toxin upon rabbits is the same, whether it is derived from
      filtrates of broth cultures (3 to 6 days old), or is obtained by autolysis of the
      killed bacteria, grown on agar surface. Rabbits show in both cases prostration,
      loss in weight, paralysis, and diarrhea. 3. When the toxin is heated to 80
      degrees C. for 1 hour, its poisonous effect nearly disappears, but its immunizing
      ability is unaltered. This heated toxin induces a formation of antitoxin, which
      can protect against the unheated toxins. 4. The anatomical changes observed in
      the spinal cord (degeneration of the motor neurons) and in the cecum (hyperemia
      and hemorrhages) are in agreement with the statements of previous authors.
      Furthermore, the toxin causes hyperemia and hemorrhages in the heart, hyperemia
      and degeneration in the kidneys and the liver.

PMID- 19870454
TI  - EXPERIMENTS ON ACTIVE IMMUNIZATION AGAINST EXPERIMENTAL POLIOMYELITIS.
AB  - The results obtained in this investigation indicate that poliomyelitis virus
      treated with tannin, sodium ricinoleate, or formalin does not constitute a
      satisfactory immunizing agent in monkeys against the experimental disease.

PMID- 19870455
TI  - THE RELATION OF LEUKOSIS TO SARCOMA OF CHICKENS : II. MIXED OSTEOCHONDROSARCOMA
      AND LYMPHOMATOSIS (STRAIN 12).
AB  - Osteochondrosarcoma developed in a chicken inoculated with leukosis of Strain 2.
      In successive passages made by intramuscular implantation of tumor tissue
      deriving from this chicken there occurred (a) osteochondrosarcoma free from
      leukosis, or (b) leukosis free from osteochondrosarcoma, or (c)
      osteochondrosarcoma in association with leukosis. The malignant sarcoma cells of
      this strain have the morphological characteristics of osteoblasts. Implantation
      of tumor tissue from chickens with lesions (a) and (c) yielded both
      osteochondrosarcoma and leukosis. Successive passages made by intravenous and
      intramuscular injections with blood from chickens with leukosis yielded leukosis
      only. Hence it is very probable that Strain 12 consists of a mixture of an
      osteochondrosarcoma-producing agent and the agent of leukosis of Strain 2. Strain
      12 is readily transmitted by material containing the living malignant osteoblasts
      but transmission is seldom successful with virus freed from living cells. This
      virus produces neoplasms only when brought in contact with bone or cartilage.

PMID- 19870456
TI  - THE RELATION OF LEUKOSIS TO SARCOMA OF CHICKENS : III. SARCOMATA OF STRAINS 11
      AND 15 AND THEIR RELATION TO LEUKOSIS.
AB  - Two transmissible sarcomata (Nos. 15 and 11) are described. Strain 15 originated
      in a chicken injected with neurolymphomatosis of Strain 5. Its virus produces
      sarcoma characterized by peculiar giant cells, different from those of the other
      known chicken sarcomata. It does not produce neurolymphomatosis or leukosis.
      Strain 11 is morphologically similar to the spindle cell sarcoma of Rous and of
      other workers. It occurred in an uninjected control chicken and its virus
      produces sarcoma unassociated with leukosis. Both Strains 11 and 15 can be
      readily transmitted with material free from viable cells and their virus can be
      preserved by drying in the frozen state. The viruses of leukosis of Strain 1 and
      sarcoma of Strain 11 when injected into the same bird retain their identity and
      can be readily reisolated.

PMID- 19870457
TI  - PATHOLOGY OF PNEUMOCOCCUS INFECTION IN MICE FOLLOWING INTRANASAL INSTILLATION.
AB  - Pneumonia can be produced in mice, which have not been previously prepared, by
      intranasal inoculation of broth cultures of certain strains of pneumococci.
      Lesions which are quantitatively different can be produced in different breeds of
      mice by inoculation of the same type of pneumococcus. Similar inoculation of
      different types of pneumococci into one breed of mice results in lesions which
      are qualitatively different. In general, these lesions are as follows: a diffuse
      pneumonia and an acute glomerular nephritis in unselected mice receiving Type I
      strains; a confluent pneumonia and a tubular nephritis in the case of Type II
      strains; and as result of Type III strains, an interstitial pneumonia with
      extensive gelatinous pleurisy, together with necrosis and abscess formation in
      the spleen and cervical lymph nodes. Resistant strains of mice with Type III
      pneumococci show slight changes in the lungs, but marked lesions in the spleen
      and cervical nodes, while susceptible mice with the same type of pneumococcus
      show marked changes in the lung and moderate lesions in the spleen and cervical
      nodes. The method of development of Type III pneumonia, studied by means of
      serial sections of nasally infected mice, appears to proceed in the stages of
      vascular engorgement, interalveolar interstitial exudate, albuminous fluid
      exudate into the alveoli and the perivascular lymphatics draining the affected
      site, and finally, a frank pneumonia with a cellular exudate in the alveoli but
      without much fibrin.

PMID- 19870458
TI  - INFECTIOUS FIBROMA OF RABBITS : III. THE SERIAL TRANSMISSION OF VIRUS MYXOMATOSUM
      IN COTTONTAIL RABBITS, AND CROSS-IMMUNITY TESTS WITH THE FIBROMA VIRUS.
AB  - In the experiments presented, Virus myxomatosum was observed to produce only a
      localized fibromatous or myxomatous orchitis when injected into the testicles of
      cottontail rabbits. This type of disease was quite unlike the acute fatal illness
      which the virus caused in domestic rabbits. 10 serial passages of Virus
      myxomatosum through cottontail rabbits, covering a total elapsed time of 140
      days, failed to alter its pathogenicity for domestic rabbits. Although it proved
      impossible to convert the myxoma virus into fibroma virus by serial passage in
      cottontail rabbits, it was found that these animals, recovered from myxoma, had a
      solid resistance to infection with the fibroma virus. Furthermore, their sera
      possessed neutralizing antibodies effective against the fibroma virus as well as
      Virus myxomatosum. A similar cross-immunological relationship was observed in the
      cases of domestic rabbits that had survived an attack of infectious myxoma.

PMID- 19870459
TI  - INFECTIOUS FIBROMA OF RABBITS : IV. THE INFECTION WITH VIRUS MYXOMATOSUM OF
      RABBITS RECOVERED FROM FIBROMA.
AB  - The serial passage of Virus myxomatosum through fibroma-recovered domestic
      rabbits did not alter its pathogenic properties. Fully virulent Virus
      myxomatosumpersisted in the inoculated testicle of fibromarecovered rabbits for
      at least 16 days following inoculation. Virus injected into the testicles of
      myxoma-immune domestic rabbits, on the other hand, was promptly rendered non
      demonstrable. The failure of fibroma-recovered domestic rabbits to destroy
      injected Virus myxomatosumand the absence from their sera of neutralizing
      antibodies effective against Virus myxomatosum are considered to be evidence
      against the identity of the fibroma and myxoma viruses. The rapidity with which
      fibroma-recovered rabbits develop neutralizing antibodies following infection
      with Virus myxomatosum is considered to be a possible factor in their acquired
      resistance. It is believed on the basis of all the evidence that infectious
      fibroma of rabbits is a definite disease entity and not merely a mild and
      nonfatal form of infectious myxoma.

PMID- 19870460
TI  - INHIBITION OF THE SHWARTZMAN PHENOMENON.
AB  - The Shwartzman phenomenon can be inhibited by an intravenous injection of a
      potent bacterial filtrate within a few hours before or after the preparatory
      intradermal injection. The inhibitory effect is produced non-specifically by
      filtrates potent in the elicitation of the Shwartzman phenomenon, and it is of a
      transitory nature. The relation of the observation described to anaphylactic
      desensitization and to its clinical significance is discussed in this paper.

PMID- 19870461
TI  - IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS : III. RESPONSE OF
      RABBITS TO INACTIVE ELEMENTARY BODIES OF VACCINIA AND TO VIRUS-FREE EXTRACTS OF
      VACCINE VIRUS.
AB  - Humoral antibodies and a certain degree of resistance to infection with vaccinia,
      probably not enduring, are produced in rabbits by the repeated injections of
      inactive formolized (0.3 per cent) elementary bodies of vaccinia and virus-free
      filtrates of dermal vaccine virus. Single injections of large amounts of
      elementary bodies are not as effective as similar amounts administered in small
      repeated doses. Drastic treatment (10 per cent formaldehyde or boiling for 2
      hours) almost completely alters or destroys the antigenicity of elementary
      bodies. It appears that the production of precipitins and agglutinins does not
      parallel that of neutralizing antibodies and that the mere presence of such
      antibodies in the serum of a rabbit as the result of injections of inactive
      elementary bodies does not necessarily indicate that the animal possesses a great
      degree of resistance to infection with a potent vaccine virus. The fact that some
      neutralizing antibodies appeared in the sera of rabbits that had received
      injections of inactive elementary bodies can be interpreted as indicating that at
      least not all neutralizing antibodies for vaccine virus are the result of a
      reaction to an antigen produced by the host in consequence of a vaccinal
      infection. No evidence was obtained to show that elementary bodies inactivated by
      our methods (0.3 per cent formaldehyde) would serve as a suitable vaccine for the
      protection of human beings against smallpox.

PMID- 19870462
TI  - THE COLONY MORPHOLOGY OF TUBERCLE BACILLI : V. INFLUENCE OF THE PH OF THE CULTURE
      MEDIUM ON COLONY FORM.
AB  - The colony topography of tubercle bacilli is significantly affected by altering
      the pH of the culture medium on which the organisms are grown. Under the
      conditions of these experiments, avian tubercle bacilli produce two variants,
      rough and smooth. The former are most numerous on the most acid medium used (pH
      6.0); the smooth colonies are obtained over a broad range of pH. Three colonial
      variants of bovine and human tubercle bacilli are described. Both mammalian types
      produce greater numbers of rough colonies at pH 6.0. The bovine type strains
      produce greatest numbers of smooth colonies in the pH range 6.4 to 6.8, and
      intermediate colonies on alkaline medium. The human type strains produce greatest
      numbers of smooth colonies at pH 6.4 and large numbers of intermediate colonies
      at pH 6.8 and pH 7.2. Included among the avian and bovine strains studied are
      organisms of widely varying pathogenic properties. Virulent and attenuated
      strains of a given type produce similar colonial variants under similar
      environmental conditions.

PMID- 19870463
TI  - A CHANGE IN RABBIT FIBROMA VIRUS SUGGESTING MUTATION : I. EXPERIMENTS ON DOMESTIC
      RABBITS.
AB  - A strain of rabbit fibroma is described causing in inoculated animals acute
      inflammatory lesions very different from the fibroma-like growths induced by the
      original strain. The new inflammatory strain cross-immunised with the normal
      strain but not with various other viruses. Efforts at changing one strain into
      the other were unsuccessful. Another, referred to as the changed, strain produced
      lesions of mixed character, partly inflammatory, partly fibromatous; it continued
      to behave in this way through numerous passages. An artificial mixture of
      inflammatory and fibromatous viruses behaved in all respects like the changed
      strain. Discussion of the significance of the findings is reserved for a separate
      paper (3) where the facts can be considered in relation to those described by
      Shope (2).

PMID- 19870464
TI  - A CHANGE IN RABBIT FIBROMA VIRUS SUGGESTING MUTATION : II. BEHAVIOR OF THE
      VARIANT VIRUS IN COTTONTAIL RABBITS.
AB  - A change in the type of lesion produced by the fibroma virus has been observed.
      At about its 18th serial transfer in domestic rabbits the virus lost its ability
      to induce fibromas when administered subcutaneously. Instead, lesions developing
      in either the subcutaneous tissue or in the testicle were predominantly
      inflammatory in character and partly composed of lymphocytes and large
      mononuclear cells in place of fibroblast-like cells. Andrewes, working with the
      same virus in England, has observed a somewhat similar change. Passage of my
      changed virus through cottontail rabbits results in a transient recovery of the
      capacity to produce fibromata, while similar passage of Andrewes' inflammatory
      virus is without effect.

PMID- 19870465
TI  - A CHANGE IN RABBIT FIBROMA VIRUS SUGGESTING MUTATION : III. INTERPRETATION OF
      FINDINGS.
AB  - A strain of rabbit fibroma virus (changed virus) producing partly fibromatous,
      partly inflammatory, lesions is believed to represent a mixture of the original
      virus with a strain (inflammatory virus) causing only necrotic and inflammatory
      lesions. The inflammatory virus does not represent a contamination from without,
      but probably arose as a mutant from the original strain. The occurrence of
      mutation amongst viruses and the propriety of using the word in this field are
      briefly discussed. Consideration is also given to the nature of the change in the
      virus which leads to a tissue reaction so widely different from that produced by
      the original strain.

PMID- 19870466
TI  - ON THE GROUP SPECIFIC A SUBSTANCE IN HORSE SALIVA. II.
AB  - A method is described for the purification of the A substance in horse saliva,
      and additional observations on the chemical properties of the preparation are
      reported. The preparation isolated was found to be highly active serologically
      and it appears to be polysaccharide in nature.

PMID- 19870467
TI  - PATHOGENESIS OF PNEUMOCOCCUS INFECTIONS IN MICE.
AB  - Unprepared mice given intranasal inoculations of certain strains of pneumococci
      develop pneumonia. The proportion of inoculated mice which will show the
      pneumonia at autopsy is dependent upon the strain and type of organism and the
      breed of mice used. It has been shown that, with the technique employed, the
      pneumococci reach the lower respiratory tract and alveoli almost immediately;
      moreover, that an invasion of the blood stream occurs very rapidly and can be
      demonstrated in a third of mice during the first 10 minutes. There is some
      evidence that invasion of the tissues and the blood stream may occur both through
      the upper respiratory tract, probably the nasal mucosa, and through the alveolar
      walls. It is uncertain which route of invasion, if either, is of the most
      importance. It has been possible to produce pneumonia by direct intravenous
      inoculation of pneumococci. It may be that the pneumonia is favored by a reaction
      at the point of invasion through the alveolar walls in the intranasally
      inoculated mice, but the results of the intravenous inoculation make it clear
      that such a local lesion is unnecessary for the production of pneumonia in mice.

PMID- 19870468
TI  - RESPIRATORY VERSUS GASTRO-INTESTINAL INFECTION IN POLIOMYELITIS.
AB  - The debated problem of gastro-intestinal versusrespiratory mode of infection in
      poliomyelitis has been restudied by several investigators recently, with
      conflicting findings. Kling and Levaditi in Europe carried out experiments from
      1929 to 1933, which led them to the conclusion that the digestive tract affords a
      ready entrance of the virus of the disease into the body. They believe that the
      substitution of Macacus cynomolgus for Macacus rhesus as the animal of choice for
      the tests supports this point of view. Toomey in the United States has arrived at
      a similar conclusion, not by employing a particular species of monkey for
      experiment, but by the use of drastic measures of inoculation, which insure that
      the virus makes contact with the unmyelinated nerve fibers embedded in the
      intestinal wall. Toomey's methods are so severe and artificial that his results
      cannot be regarded as simulating a natural mode of infection. We have repeated
      the tests of Kling and Levaditi, but in a far more comprehensive manner than was
      followed by them, and, like Clark and his associates who early repeated them, we
      have failed to confirm them. Indeed, we do not find Macacus cynomolgusand rhesus
      to differ in any essential way in their response to the presence of the virus of
      poliomyelitis in the body. Cynomolgido not respond to virus introduced into the
      stomach when contamination of the buccal and nasal cavities is avoided; they
      respond, as do rhesi, to virus directly injected into the intestine when virus
      passes into the intestinal wall and makes the necessary nerve fiber contact. Both
      Macacus cynomolgus and Macacus rhesus which have resisted feedings of virus are
      subject to nasal instillations of the same strains of virus and in the same
      degree. On the basis of the experiments reported in this paper we can reaffirm
      the conclusion previously arrived at by ourselves, and confirmed independently by
      investigators in Europe and America, namely that the only established portal of
      entry of the virus of poliomyelitis into the central nervous system of man is the
      nasal membrane, and especially the olfactory nervous areas in that membrane.

PMID- 19870469
TI  - A STUDY OF GENERALIZED VACCINIA IN THE CHICK EMBRYO.
AB  - 1. Chick embryos infected by the chorio-allantoic route with a bacteria-free
      strain of vaccinia virus develop a general dissemination of the virus throughout
      the entire organism with the exception of the central nervous system. 2.
      Quantitative estimation of the distribution of the virus in the various organs of
      the infected chick by cutaneous inoculation on the rabbit skin offers no evidence
      for a heightened affinity of the virus for special tissues. 3. Histological study
      of the lesions in the various organs demonstrates the focal character of the
      lesions which apparently originate as perivascular infiltrations around the
      smaller blood vessels. No lesions could be demonstrated in the central nervous
      system proper. 4. In the earlier stages of the disease Guarnieri bodies are
      clearly demonstrable in the cells of the epidermis and the squamous epithelium of
      the buccal mucosa. Inclusion bodies closely resembling Guarnieri bodies are
      demonstrated in all the lesions occurring in the various other organs. 5. It was
      not possible to demonstrate conclusively the presence of Paschen bodies in the
      lesions of the internal organs by the Morosow method usually used for the
      demonstration of these bodies in the membranal lesion.

PMID- 19870470
TI  - STUDIES ON THE ETIOLOGY OF RABBIT POX : I. ISOLATION OF A FILTERABLE AGENT: ITS
      PATHOGENIC PROPERTIES.
AB  - A filterable agent was isolated from 7 cases of spontaneous rabbit pox by the
      intratesticular injection in rabbits of a variety of tissues. The virus was
      transmitted for 15 consecutive testicle to testicle passages in rabbits by
      Berkefeld V filtrates of testicular tissue emulsions. Unfiltered emulsions were
      more potent than filtrates. The virulence of the virus was maintained by ice box
      storage of infected tissues for as long as 127 days. The pathogenic properties of
      the virus persisted under conditions of animal passage for the 9 months from
      January to October, 1933, covered by these studies. The reaction produced in
      rabbits by the inoculation of tissue-virus emulsions was of two principal types,
      the first of which has been described and analyzed in the present paper. In the
      case of intratesticular injections, particularly of testicular tissue inocula, an
      acute fulminating and rapidly fatal condition regularly developed. The
      outstanding features were a massive hemorrhagic orchitis with marked scrotal
      edema, fever, and death within a week. The second type of reaction which is taken
      up in the next paper of this series (1) was observed under conditions in which
      the animal survived a week or longer. Occasional examples occurred in rabbits of
      the so called intratesticular series. The reaction was characterized by the
      development of a disease syndrome with a diversity of clinical manifestations
      which, it may be stated here for the sake of continuity, was indistinguishable
      from spontaneous rabbit pox.

PMID- 19870471
TI  - STUDIES ON THE ETIOLOGY OF RABBIT POX : II. CLINICAL CHARACTERISTICS OF THE
      EXPERIMENTALLY INDUCED DISEASE.
AB  - The clinical manifestations and course of disease observed in experimental rabbit
      pox have been described and analyzed. The condition differed from the acute
      fulminating and rapidly fatal type of experimental infection (1) in that the
      period of survival was longer, a variety of clinical manifestations developed and
      a considerable proportion of the cases recovered. The most conspicuous symptom
      was a generalized papular eruption on the skin and mucocutaneous borders. The
      production of the disease was associated with routes of inoculation other than
      the intratesticular or with a small dosage. The majority of cases were inoculated
      with Berkefeld V filtrates of tissue-virus emulsions and not with the more potent
      unfiltered emulsions. The local reactions resulting from various routes of
      inoculation were described. Of special interest were the pronounced cutaneous
      reactions induced by intradermal injection, the high instance of marked clinical
      manifestations after intravenous inoculation, the failure of lesions to localize
      in the lines of scarification of skin and cornea even in cases with a profuse
      cutaneous eruption, and the development of cytoplasmic inclusion bodies in the
      epithelial cells of the cornea following scarification and conjunctival
      instillation of virus. In the character of its clinical manifestations and course
      of disease, experimental rabbit pox was indistinguishable from cases of the
      spontaneous pox.

PMID- 19870472
TI  - BLOOD PLASMA PROTEIN REGENERATION CONTROLLED BY DIET : EFFECTS OF PLANT PROTEINS
      COMPARED WITH ANIMAL PROTEINS THE INFLUENCE OF FASTING AND INFECTION.
AB  - When blood plasma proteins are depleted by bleeding, with return of washed red
      cells (plasmapheresis), it is possible to bring the dog to a steady state of low
      plasma protein in the circulation and a uniform plasma protein production on a
      basal diet. These dogs become test subjects by which the potency of various diet
      factors for plasma protein regeneration can be measured. Plant and grain proteins
      are quite well utilized to form new plasma protein in these test dogs but soy
      bean meal probably should be rated at the head of this list. It is utilized with
      unexpected promptness and favors the production of albumin in contrast to other
      plant proteins which distinctly favor globulin production. Long plasmapheresis
      periods on basal rations rich in grain proteins lower the resistance of these
      animals to infection. Spleen, brain, and stomach when fed with the basal diet in
      these test dogs show less favorable potency ratios-10.2, 11.8, and 13.6
      respectively. This means the grams of tissue protein which must be fed to produce
      1 gm. of new plasma protein. Fasting periods indicate that the dog can contribute
      only 4 to 6 gm. of plasma protein each week-an insignificant contribution
      presumably derived from the host's tissue proteins. Infection and intoxication
      disturb the plasma protein production of these standardized dogs and may reduce
      the output of plasma proteins to very low levels in spite of considerable food
      intake. There may be a very sharp drop in the plasma protein level during the
      first day of intoxication (Dog 33-324). Some of these observations may be of
      value in a study of clinical conditions associated with hypoproteinemia.

PMID- 19870473
TI  - THE VISCERAL LESIONS PRODUCED IN MICE BY THE SALIVARY GLAND VIRUS OF MICE.
AB  - Extensive visceral lesions containing intranuclear inclusions have been produced
      in mice by intraperitoneal and intracerebral inoculations of the homologous
      salivary gland virus. Rarely small pancreatic lesions containing inclusions have
      been encountered 2 weeks after subcutaneous inoculation. Many of the animals
      injected intraperitoneally died between the 4th and 7th day after inoculation. In
      spite of the extensive lesions produced in the liver and spleen, the virus could
      not be transferred with an emulsion of these organs.

PMID- 19870474
TI  - ACTIVE IMMUNICATION OF GUINEA PIGS WITH THE VIRUS OF EQUINE ENCEPHALOMYELITIS :
      I. QUANTITATIVE EXPERIMENTS WITH VARIOUS PREPARATIONS OF ACTIVE VIRUS.
AB  - Active Eastern or Western equine encephalomyelitis virus in three forms,
      chemically untreated but simply passaged through series of mice; adsorbed on
      alumina Gel C, and precipitated by tannin,-yielded practically the same results
      when employed for the immunization of guinea pigs. The virus is not inactivated
      by the process of adsorption or precipitation : guinea pigs and mice inoculated
      in the brain with these materials develop lethal encephalomyelitis in the same
      manner as when chemically untreated mouse passage virus has been used. Moreover,
      there is no difference in the rate of absorption in vivoof the chemically treated
      and untreated virus preparations. After storage of the three immunizing
      preparations-the longest periods thus far studied being 2 to 3 months for mouse
      passage and for precipitated suspensions, and 6 months for adsorbed material-each
      was found to contain an amount of virus sufficient to produce immunity in animals
      against the usual intracerebral test inoculation. Finally, the protection
      afforded by the three preparations is apparently durable, as is true of many
      active viruses utilized in preventive treatments. The amount of the virus
      necessary to confer protection may be defined as that which immunizes (a) with
      the least number of antigenic units and (b) with the minimum of febrile reaction
      and blood infection. In proportion as this amount is exceeded, the incidence of
      fever and of circulating virus increases and, on the other hand, as this amount
      is decreased, the degree of induced immunity is diminished. We have thus shown
      that for this particular virus and in the guinea pig, one or two subcutaneous
      doses of I cc. of any of the different virus preparations, each containing 3 x
      10(3) to 3 x 10(4) mouse infective units, bring about protection regularly
      against experimental infection by way of the nose or subcutis. The results are
      irregular when the test is made by way of the brain. By three injections,
      resistance is invariably obtained against as many as 10(3) to 10(4) lethal doses,
      given intracerebrally. No matter in what form the virus is given, as mouse
      passage, or adsorbed, or precipitated material, in certain instances fever occurs
      and virus circulates. With the amount of virus adequate for immunization (3,000
      to 30,000 m.i.u.) a mild or subclinical infection may occur in the guinea pig
      without other manifestation of disease. Lesser quantities of virus apparently
      fail to gain a foothold in the animal and thus fail to bring about resistance. To
      conclude, a quantitative basis has been established for the comparison of the
      immunizing capacities of preparations employed in experimental equine
      encephalomyelitis in guinea pigs.

PMID- 19870475
TI  - ON CROSS REACTIONS OF IMMUNE SERA TO AZOPROTEINS.
AB  - The phenomena observed on absorption of immune sera to azoproteins with
      heterologous azoantigens lead to the conclusion that in general the sera do not
      contain a single antibody but antibody fractions somewhat different in their
      reactivity for heterologous antigens. From the constitution of the azocomponent
      it follows that these fractions cannot be specific for distinct chemical groups
      in the molecule. In fact, inhibition experiments showed that in the cases
      examined the various antibodies are all specifically directed towards the whole
      molecule of the homologous hapten.

PMID- 19870476
TI  - STUDIES ON CULTURE STRAINS OF EUROPEAN AND MURINE TYPHUS.
AB  - 1. A strain of European typhus (Breinl) has been carried in cultures by means of
      successive transfers for a period of 1(1/2) years, the rickettsiae in such
      cultures being quite as numerous as in similar cultures of murine strains of
      typhus. 2. The virulence of the cultures of European typhus has remained constant
      throughout the period of cultivation, although, on the whole, the scrotal lesions
      caused by the later culture generations were somewhat less marked than those
      produced by the first generations. 3. A strain of murine typhus has been
      similarly carried in cultures for 4 years with no apparent loss in pathogenicity.
      4. The characteristic scrotal lesion in murine typhus in guinea pigs is
      apparently referable to actual predilection of this strain for the tunica tissue
      rather than to the number of rickettsiae injected.

PMID- 19870477
TI  - STUDIES ON THE ETIOLOGY OF RABBIT POX : III. TESTS OF THE RELATION OF RABBIT POX
      VIRUS TO OTHER VIRUSES BY CROSSED INOCULATION AND EXPOSURE EXPERIMENTS.
AB  - Experiments are reported in which it was shown that rabbits which had recovered
      from experimental or spontaneous rabbit pox were refractory to inoculation of pox
      virus injected by various routes, and in addition did not develop clinical
      manifestations of the disease under conditions of exposure to florid cases of
      pox. It was found that pox recovered rabbits were susceptible to inoculation with
      the virus of virus III disease of rabbits and that virus III recovered rabbits
      could be successfully inoculated with pox virus. Furthermore, virus III recovered
      rabbits developed pox when subjected to room exposure in the same manner as did
      normal rabbits. It thus appears that there is no specific relationship between
      the two viruses. Rabbits which had recovered from experimental or spontaneous pox
      were found to be just as susceptible to inoculation with the virus of infectious
      myxoma of rabbits as were normal rabbits, a result which demonstrates that there
      is no specific relationship between these viruses. Rabbits which had recovered
      from experimental or spontaneous pox were refractory to inoculation with culture
      dermovaccine virus, but vaccine recovered rabbits were not completely refractory
      to inoculation with pox virus. Under conditions of exposure to clinical cases of
      pox, adult vaccine immune rabbits did not develop clinical manifestations of pox,
      but young, recently weaned vaccinated rabbits did contract mild but definite
      clinical pox. Experimental pox recovered rabbits were partially refractory to
      inoculation with neurovaccine virus and neurovaccine recovered rabbits were
      partially refractory to inoculation with pox virus. The refractory condition of
      the pox immune rabbits appeared to be more pronounced than that of the
      neurovaccine immunes. The cutaneous lesions which developed from the intradermal
      injection of pox, neurovaccine, and culture vaccine viruses showed definite
      differences with respect to the rate and persistence of active growth, amount of
      edema, hemorrhage, and necrosis, and the degree of tissue destructiveness. These
      features were most pronounced in the lesions of pox virus and were least marked
      in the lesions of culture vaccine virus. The differences were particularly
      apparent in normal rabbits, but they were also present in the lesions which
      developed in immune animals. It was found that the calf was susceptible to
      inoculation with pox virus applied to a scarified skin area. There were many
      similarities in the appearance and course of the pox lesions to those resulting
      from culture vaccine virus, the New York Board of Health vaccine, and
      neurovaccine virus similarly inoculated. But the pox lesions were most numerous,
      much the largest and most destructive, and by far the most persistent while next
      in order were those of the Board of Health dermovaccine. The results of these
      various experiments showed that a close relationship obtains between pox virus,
      on the one hand, and vaccine virus and neurovaccine virus, on the other, but it
      cannot be said that pox virus is identical in all respects with either one of
      these viruses. The findings indicated that the relationship between pox and
      neurovaccine viruses is closer than that between pox and culture vaccine viruses.
      Upon the basis of the results observed in culture (dermo) vaccine immune rabbits
      inoculated with or exposed to pox, it appeared that vaccination with vaccine
      virus offered a method of protection against rabbit pox.

PMID- 19870478
TI  - STUDIES ON THE ETIOLOGY OF RABBIT POX : IV. TESTS ON THE RELATION OF RABBIT POX
      VIRUS TO OTHER VIRUSES BY SERUM NEUTRALIZATION EXPERIMENTS.
AB  - The results of serum neutralizing tests with the viruses of pox, vaccinia, and
      virus III disease herewith reported generally agree and supplement the results of
      reinoculation experiments on immune rabbits reported in the previous paper (1).
      The finding that pox virus is neutralized by pox immune serum indicates that the
      refractory state of recovered pox rabbits to reinoculation with pox virus and the
      failure of recovered pox rabbits to contract a second pox infection after
      adequate exposure is to be explained upon the basis of the development of an
      active immunity. The failure of virus III immune serum to neutralize pox virus is
      in agreement with the previous conclusion drawn from the positive results of
      reinoculation and exposure experiments that there is no specific relationship
      between pox virus and virus III. Rabbits which had recovered from a pox infection
      were completely refractory to inoculation with dermo-(culture) vaccine, while
      rabbits which had recovered from vaccinia were partially refractory to
      inoculation with pox virus. Vaccine immune adult rabbits did not show any
      clinical evidence of pox upon exposure to florid cases, but young recently weaned
      vaccine immunes developed definite although comparatively mild pox infections.
      The serum neutralization tests showed that pox immune serum neutralized vaccine
      virus although the action was not complete as shown by the positive results
      obtained with high dilutions of serum; vaccine immune serum possessed some but
      comparatively slight neutralizing properties against pox virus. The results of
      the crossed inoculation and serum neutralizing experiments with pox and
      neurovaccine viruses resembled those obtained with pox and dermo-(culture)
      vaccine but the differences were less pronounced. The differences in virus
      neutralizing ability on the part of the three immune sera paralleled the
      differences in virus potency as indicated by the character of the local lesions
      at the site of injection and by the general character of the clinical
      manifestations of the infection. The potency or virulence of pox virus was much
      greater than that of neurovaccine and vastly greater than that of dermo-(culture)
      vaccine. The complete identity of pox and vaccine virus could not be established,
      but a definite relationship between them was demonstrated and this was shown to
      have an immunological basis. From a practical standpoint vaccination with vaccine
      virus as a prophylactic measure against rabbit pox was clearly indicated.

PMID- 19870479
TI  - MENINGITIS IN MAN CAUSED BY A FILTERABLE VIRUS : I. TWO CASES AND THE METHOD OF
      OBTAINING A VIRUS FROM THEIR SPINAL FLUIDS.
AB  - The clinical pictures presented by two men suffering from an acute bacteria-free
      lymphocytic meningitis, and the method of obtaining a virus from their spinal
      fluids were described. Evidence was then adduced to show that the virus was
      really in the spinal fluids, that the strains of virus obtained from the two
      patients were identical or closely related, and that the active agent in the
      spinal fluids was etiologically significant.

PMID- 19870480
TI  - MENINGITIS IN MAN CAUSED BY A FILTERABLE VIRUS : II. IDENTIFICATION OF THE
      ETIOLOGICAL AGENT.
AB  - Evidence was presented substantiating the idea that our active agent is a virus.
      The reactions produced in laboratory animals by the active agent were described,
      and a comparison of it with other viruses was made. The results of experiments
      indicating the immunological identity of our virus, Armstrong and Lillie's virus
      of lymphocytic choriomeningitis, and Traub's virus were given in detail. Finally,
      the evidence in regard to its natural host and its importance as a factor in
      diseases of human beings was presented and discussed.

PMID- 19870481
TI  - THE LIMITED NEUROTROPIC CHARACTER OF THE ENCEPHALITIS VIRUS (ST. LOUIS TYPE) IN
      SUSCEPTIBLE MICE.
AB  - 1. St. Louis encephalitis virus injected intracerebrally into susceptible mice
      multiplies there to reach a titre of 10(9) intracerebral lethal doses. It is
      found also in the blood in small amounts immediately following injection and
      preceding death. 2. Injected intraperitoneally or subcutaneously the virus
      circulates in the blood for several hours and survives in the spleen for days. It
      does not multiply in the brain and cause encephalitis, however, unless
      overwhelming doses are injected or the brain is traumatized. 3. Virus dropped
      into the nares is demonstrable in the olfactory bulbs at 24 hours, in the
      piriform lobes at 24 to 48 hours, in the remainder of the brain at 3 days, and in
      the spinal cord at 4 days. In the brain it reaches a titre of 10(9) in 6 days.
      Virus is not readily demonstrable in the blood but is present in the spleen after
      48 hours. 4. Virus survives and is capable of multiplying in the spleen. 5.
      Lesions following nasal instillation of virus appear first in the olfactory bulbs
      on the 3rd day, in the piriform lobes on the 4th, and in Ammon's horn on the 5th
      day. The character of the lesions in order of their appearance is exudation of
      mononuclear cells about superficial blood vessels and in the pia, hyperplasia of
      the endothelium of the pia, and necrosis of nerve cells of the olfactory tract.

PMID- 19870482
TI  - STUDIES ON PSEUDORABIES (INFECTIOUS BULBAR PARALYSIS, MAD ITCH : III. THE DISEASE
      IN THE RHESUS MONKEY, MACACA MULATTA.
AB  - In the monkey (M. mulatto) the virus of pseudorabies, pantropic in the rabbit,
      behaves as a strict neurotrope. Infection, usually fatal, readily follows
      intracerebral and intracisternal inoculation of rabbit virus, and often
      intrasciatic inoculation; the symptomatology of the ensuing disease is described.
      In a limited number of experiments no infection resulted from intradermal,
      intramuscular or intravenous inoculation. Nerve and glial cells are primarily
      attacked by the virus, but no cytological or other evidence of susceptibility of
      non-nervous tissue or of growth of virus outside the nervous system was obtained.
      Certain cortical areas, of which the principal are the pyriform area, cornu
      Ammonis, island of Reil, lower lip of the Sylvian fissure and basal surface of
      the frontal lobe, are affected far more severely than are other parts of the
      nervous axis; the reasons for this elective distribution of the most severe
      lesions, seen alike after intracerebral and intrasciatic inoculation and
      analogous perhaps to that in poliomyelitis and louping-ill, are not obvious.
      Other areas of the nervous system are relatively insusceptible to the action of
      the virus. Cases showing clinically only a febrile reaction without definite
      nervous symptoms may later exhibit marked residual lesions at the sites of
      election. The blood and cerebrospinal fluid play no apparent role in
      disseminating the virus, which, after intrasciatic inoculation, spreads upwards
      by the nervous path. Some suggestion was received from the experiments that in
      monkeys possessed of immunity to B virus (Sabin and Wright, 1934) pseudorabic
      infection is less likely to prove fatal than in animals not so immune, but the
      observations made were insufficiently numerous to be of statistical value. The
      sera of 6 out of 26 monkeys were found to contain antibodies neutralising B
      virus; these 6 monkeys were all included in one batch of 7 received at one time
      from the dealer.

PMID- 19870483
TI  - THE EFFECTS OF ADRENALECTOMY AND HYPOPHYSECTOMY UPON EXPERIMENTAL DIABETES IN THE
      CAT.
AB  - 1. The hypophysectomized cat shows an alleviation of the diabetes following
      pancreatectomy comparable to that previously demonstrated by others in the dog.
      2. It is possible by various procedures to remove both adrenals and all the
      pancreas from cats. Such animals have survived for as long as 4 weeks without the
      use of insulin, the average survival being 18 days. Daily injections of cortical
      extract are necessary. By contrast, cats deprived of insulin by similar
      procedures but with adrenals intact survive only 4-5 days. 3. Adrenalectomized
      depancreatized cats show as striking an alleviation of the diabetes as do those
      hypophysectomized and depancreatized. This is expressed by the markedly decreased
      glucose, nitrogen and acetone body excretion compared to that found in the
      depancreatized cat, as well as by the increased survival period. 4. Removal of
      epinephrine by denervation or demedullation of the adrenals does not protect
      against pancreatic diabetes in the cat. 5. The carbohydrate tolerance of
      depancreatized cats is not significantly increased by hypophysectomy or
      adrenalectomy. The exceptions to this finding have all been in animals presenting
      varying degrees of spontaneous hypoglycemia. 6. It is our opinion that the
      effects of hypophysectomy or adrenalectomy upon pancreatic diabetes are due to
      diminution of the production of glucose and acetone bodies rather than to the
      resumption of normal carbohydrate utilization.

PMID- 19870484
TI  - STUDIES ON THE ETIOLOGY OF RABBIT POX : V. STUDIES ON SPECIES SUSCEPTIBILITY TO
      RABBIT POX VIRUS.
AB  - The white mouse, the guinea pig, the calf, and probably the rat, were found to be
      susceptible to infection with the virus of rabbit pox. Serial transmission of the
      virus in mice by brain to brain passage was characterized by a fatal outcome
      usually on the 5th or 6th day after inoculation. Infection of the guinea pig was
      accomplished by intratesticular injection and the virus was continued to the 2nd
      passage in this species. Guinea pigs developed a well marked cutaneous reaction
      from the intradermal injection of both rabbit and guinea pig tissue virus. Active
      virus was demonstrated in the testicles of rats 8 days after intratesticular
      injection by rabbit subinoculation. In the calf inoculation of the scarified skin
      was followed by the development of large papular lesions with marked hemorrhage
      and necrosis. The results of the investigations on the etiology of rabbit pox and
      of the experimentally induced infection reported in this and the four preceding
      papers (1-4) are discussed with special reference to the relation of pox virus to
      other viruses and of rabbit pox to other pock diseases.

PMID- 19870485
TI  - STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL : V. A CORYZA OF SLOW
      ONSET.
AB  - A strain of fowl coryza of slow onset was carried through 20 successive passages
      in susceptible birds over a period of approximately 19 months. During this period
      it retained its initial characteristics as did also a coryza of rapid onset which
      was similarly maintained. 88 per cent of 72 birds infected with the coryza of
      slow onset showed a nasal discharge after an incubation period of 12 days or
      more; the actual limits being 9 to 31 days. 98 per cent of 54 birds infected with
      the coryza of rapid onset showed a nasal discharge on the 1st or 2nd day after
      injection. The duration of both coryzas was prolonged. Bacteriological
      examination indicated that Hemophilus gallinarum which is invariably present in
      the nasal exudate of birds infected with the coryza of rapid onset is not
      associated with the coryza of slow onset.

PMID- 19870486
TI  - STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL : VI. COCCOBACILLIFORM
      BODIES IN BIRDS INFECTED WITH THE CORYZA OF SLOW ONSET.
AB  - Minute coccobacilliform bodies have regularly been found in the nasal exudate of
      fowl infected both by injection and by contact with the coryza of slow onset.
      These bodies are commonly less than 0.5micro in diameter and are predominantly
      extracellular. They have consistently failed to grow in artificial media. They
      are held back by Berkefeld V filters which are impermeable to Hemophilus
      gallinarum but may pass through filters which are permeable to the test organism.
      The coccoid bodies are morphologically similar to a cultivable non-infective
      bacterium which may occasionally be isolated from exudate of the infected fowls.

PMID- 19870487
TI  - CONCERNING THE RELATION OF ENVIRONMENTAL TEMPERATURE TO RESISTANCE TO THYROID AND
      THYROXINE, AND THE CREATINE CONTENT OF THE HEART AND OTHER TISSUES IN
      EXPERIMENTAL HYPERTHYROIDISM.
AB  - Experiments have shown that the survival period of thyrotoxic rats is markedly
      influenced by the environmental temperature, being of much longer duration at low
      than at high temperatures. Between 22 degrees and 37.5 degrees C., the relation
      of temperature to the survival period is approximately linear. The tolerance to
      relatively large doses of thyroid and thyroxine is considerably increased below
      20 degrees C., but is especially striking at 4-6 degrees C. Hyperplasia of the
      thyroid, which results from exposure to cold, may be prevented by the
      administration of desiccated thyroid or thyroxine. The diminished concentration
      of creatine of the myocardium, which is a conspicuous finding in rats treated
      with thyroid substance, does not occur in physiological hyperthyroidism resulting
      from long continued exposure to a low thermal environment. In rats kept at high
      temperatures, whether treated with thyroid substance, or not, there is apparently
      no storage of colloid in the gland. The significance of the relatively high
      values for heart creatine in these animals at time of death is briefly discussed.